PMID- 21938430
TI  - A folate receptor alpha double-mutated haplotype 1816delC-1841A is distributed
      throughout Eurasia and associated with lower erythrocyte folate levels.
AB  - Folate is crucial for various cellular functions. Several transport mechanisms
      allow folate to enter the intracellular compartment with folate receptor-alpha
      being the major high-affinity receptor. Rare genetic variations in exons of the
      FR-alpha gene, FOLR1, were recently shown to cause severe folate deficiency
      accompanied by neurological and other disturbances. So far, similar effects by
      genetic variation in noncoding parts of the FOLR1 gene have not been identified.
      The aim of our study was to determine biochemically the haplotype structure of
      two linked polymorphisms in the FOLR1 gene, 1816delC and 1841G>A, the prevalences
      of the mutated alleles across Eurasia, and their possible effects on
      physiological folate levels in vivo. For this purpose we employed allele-specific
      PCR and Pyrosequencing technology and performed genotyping in 738 subjects from
      Spain, 387 from Sweden, 952 from Estonia, and 47 from Korea. We demonstrate the
      presence of an ancient double-mutated haplotype 1816delC-1841A in the FOLR1 gene,
      with the prevalence of the mutated allele being highest among Koreans (q =
      0.074), lower in Estonians (q = 0.017), Spaniards (q = 0.0061), and the lowest
      among Swedes (q = 0.0026). Erythrocyte folate levels were studied in the Spanish
      population sample, where subjects carrying the double-mutated FOLR1 haplotype had
      significantly reduced levels by 27% (P = 0.039), adjusted for serum vitamin B(12)
      levels and MTHFR 677C>T genotype, while the mean serum folate levels were only
      20% lower among the carriers (P = 0.11). Plasma homocysteine and cobalamin levels
      did not differ. Thus, we have demonstrated by molecular haplotyping an ancient
      double-mutated haplotype 1816delC-1841A in the FOLR1 gene, spread over the whole
      Eurasian continent, which may be of functional importance for uptake of folate in
      red blood cells.

PMID- 21938429
TI  - A novel cold-inducible gene from Pak-choi (Brassica campestris ssp. chinensis),
      BcWRKY46, enhances the cold, salt and dehydration stress tolerance in transgenic
      tobacco.
AB  - WRKY TFs belong to one of the largest families of transcriptional regulators in
      plants and form integral parts of signaling webs that modulate many plant
      processes. BcWRKY46, a cDNA clone encoding a polypeptide of 284 amino acids and
      exhibited the structural features of group III of WRKY protein family, was
      isolated from the cold-treated leaves of Pak-choi (Brassica campestris ssp.
      chinensis Makino, syn. B. rapa ssp. chinensis) using the cDNA-AFLP technique.
      Expression of this gene was induced quickly and strongly in response to various
      environmental stresses, including low temperatures, ABA, salt and dehydration.
      Constitutive expression of BcWRKY46 in tobacco under the control of the CaMV35S
      promoter reduced the susceptibility of transgenic tobacco to freezing, ABA, salt
      and dehydration stresses. Our studies suggest that BcWRKY46 plays an important
      role in responding to ABA and abiotic stress.

PMID- 21938431
TI  - DNMT3B polymorphisms and cancer risk: a meta analysis of 24 case-control studies.
AB  - The association between polymorphism of DNA methyltransferases 3B and cancer risk
      has been widely studied recently, and no consensus conclusion is available up to
      now. We perform a comprehensive search using the databases of Medline, ISI Web of
      Knowledge and Embase. The odds ratio (OR) and its 95% confidence interval (95%
      CI) are used to investigate the strength of the association. A total of 24 case
      control studies with 15,647 individuals are included in this meta-analysis. For 
      149C > T (17 studies, 5229 cases and 6910 controls), no evidence indicate that
      individuals carrying the variant genotypes (CC + CT), relative to those carrying
      the wild homozygote TT genotype, have an increased risk of cancer (OR = 1.03; 95%
      CI = 0.84-1.26; P = 0.76). Similarly, no cancer risk is found in the subgroup
      analyses. For -579G > T (11 studies, 3513 cases and 3714 controls), significantly
      decreased risks of cancer are observed, and the ORs (95% CI) are 0.70 (0.56-0.87)
      for GT versus TT, 0.70 (0.57-0.85) for GG + GT versus TT and 0.76 (0.63-0.93) for
      G-allele versus T-allele, respectively. Subgroup analyses stratified by ethnicity
      and types of cancer are also performed, and results indicated that -579G > C
      polymorphism is associated with risk of cancer in Asians [0.68 (0.53-0.87) for GT
      vs. TT] but not in Europeans [0.82 (0.63-1.07) for GT vs. TT]. We also observe
      that the -579G is associated with decreased risk of colorectal cancer [0.49(0.38
      0.62) for GT vs. TT]. More studies with larger sample size were needed to provide
      more precise evidence.

PMID- 21938432
TI  - SEPT4 is regulated by the Notch signaling pathway.
AB  - Notch receptor-mediated signaling is an evolutionarily conserved pathway that
      regulates diverse developmental processes and its dysregulation has been
      implicated in a variety of developmental disorders and cancers. Notch functions
      in these processes by activating expression of its target genes. Septin 4 (SEPT4)
      is a polymerizing GTP-binding protein that serves as scaffold for diverse
      molecules and is involved in cell proliferation and apoptosis. After activation
      of the Notch signal, the expression of SEPT4 is up-regulated and cell
      proliferation is inhibited. When the Notch signal is inhibited by the CSL
      (CBF1/Su(H)/Lag-1)-binding-domain-negative Mastermind-like protein 1, the
      expression of SEPT4 is down-regulated, proliferation and colony formation of
      cells are promoted, but cell adhesion ability is decreased. Nevertheless, the
      SEPT4 expression is not affected after knock-down of CSL. Meanwhile, if SEPT4
      activity is inhibited through RNA interference, the protein level and activity of
      NOTCH1 remains unchanged, but cell proliferation is dysregulated. This indicates
      that SEPT4 is a Notch target gene. This relationship between Notch signaling
      pathway and SEPT4 offers a potential basis for further study of developmental
      control and carcinogenesis.

PMID- 21938433
TI  - Synthesis and expression of recombinant interferon alpha-5 gene in tobacco
      chloroplasts, a non-edible plant.
AB  - The production of interferon alpha from microbial to mammalian expression system,
      have certain precincts in terms of cost, scalability, safety and authenticity.
      Modern biotechnology exploits transgenic crops to get large quantities of complex
      proteins in a cost-effective way. In order to overcome several challenges from
      biosafety point of view, the chloroplast transformation strategy is one of the
      best approaches since plastids are strictly maternally inherited in most of the
      cultivated species. In the present study the interferon alpha 5 gene was
      synthesized by using complex set of oligos. After sequence confirmation of the
      synthesized gene, the histidine residues along with the thrombin protease site
      were engineered upstream to the synthetic interferon alpha 5 gene. The
      recombinant fragment was then tethered with chloroplast light inducible promoter,
      rbcl followed by sequential cloning to develop chloroplast transformation vector
      to target the cassette into the inverted repeat region of plastome through two
      events of homologous recombination. The putative transgenic plants obtained
      through biolistic delivery method and as a result of antibiotic selection of
      bombarded leaves, were subjected to different rounds of selection and
      regeneration for homoplasmicity. The spectinomycin-resistant shoots were analyzed
      through Polymerase Chain Reaction and Sothern blotting. The expression of
      introduced synthetic genes was recorded using Enzyme Linked ImmunoSorbant Assay
      technique. It was experienced that mature leaves contained comparatively high
      levels of interferon compared to young and senescence leaves.

PMID- 21938434
TI  - Comparing interfertility data with random amplified microsatellites DNA (RAMS)
      studies in Ganoderma Karst. Taxonomy.
AB  - The taxonomy of the causal pathogen of basal stem rot of oil palms, Ganoderma is
      somewhat problematic at present. In order to determine the genetic distance
      relationship between G. boninense isolates and non-boninense isolates, a random
      amplified microsatellites DNA (RAMS) technique was carried out. The result was
      then compared with interfertility data of G. boninense that had been determined
      in previous mating studies to confirm the species of G. boninense. Dendrogram
      from cluster analysis based on UPGMA of RAMS data showed that two major clusters,
      I and II which separated at a genetic distance of 0.7935 were generated. Cluster
      I consisted of all the biological species G. boninense isolates namely CNLB, GSDK
      3, PER 71, WD 814, GBL 3, GBL 6, OC, GH 02, 170 SL and 348781 while all non
      boninense isolates namely G. ASAM, WRR, TFRI 129, G. RES, GJ, and CNLM were
      grouped together in cluster II. Although the RAMS markers showed polymorphisms in
      all the isolates tested, the results obtained were in agreement with the
      interfertility data. Therefore, the RAMS data could support the interfertility
      data for the identification of Ganoderma isolates.

PMID- 21938435
TI  - Gender difference in snoring and how it changes with age: systematic review and
      meta-regression.
AB  - PURPOSE: The aim of this study was to study the interactions among age, gender,
      and snoring across all age groups METHODS: All cross-sectional study reporting
      gender-specific prevalence of snoring in general population published from 1966
      through July 2008 were included and were meta-analyzed. The sources of
      heterogeneity among primary studies were studied by meta-regression. RESULTS:
      From a total of 1,593 citations reviewed, 63 were included in the analysis of
      snoring. These 63 studies were comprised 104,337 and 110,474, respectively. A
      combined odds ratio of 1.89 with a 95% confidence interval of 1.75-2.03 for male
      versus female was found. The heterogeneity was significant with an estimated
      between-study variance, tau (2) being 0.065 and 95% confidence interval of 0.0397
      0.0941. Multiple meta-regression showed that age were the significant effect
      modifier of the relationship between snoring and gender. CONCLUSION: This study
      found a consistent male predominance in snoring among the general population, and
      the heterogeneity in the risk of snoring between two genders can be partly
      explained by age.

PMID- 21938436
TI  - Complete denture wear during sleep in elderly sleep apnea patients--a preliminary
      study.
AB  - OBJECTIVES: There is no consensus in the literature about the impact of complete
      denture wear on obstructive sleep apnea (OSA). The goal of this randomized
      clinical study was to assess if complete denture wear during sleep interferes
      with the quality of sleep. MATERIALS AND METHODS: Elderly edentulous OSA patients
      from a complete denture clinic were enrolled and received new complete dentures.
      An objective sleep analysis was determined with polysomnography performed at the
      sleep laboratory for all patients who slept either with or without their
      dentures. RESULTS: Twenty-three patients (74% females) completed the study with a
      mean age of 69.6 years and a mean body mass index of 26.7 kg/m(2). The apnea and
      hypopnea index (AHI) was significantly higher when patients slept with dentures
      compared to without (25.9 +/- 14.8/h vs. 19.9 +/- 10.2/h; p > 0.005). In the mild
      OSA group, the AHI was significantly higher when patients slept with the dentures
      (16.6 +/- 6.9 vs. 8.9 +/- 2.4; p < 0.05), while in moderate to severe OSA
      patients, the AHI was not significantly different when sleeping with dentures
      (.30.8 +/- 15.6 vs. 25.7 +/- 7.5; p = 0.2). The supine AHI in mild patients was
      related to a higher increase in AHI while wearing dentures (12.7 +/- 8.4/h vs.
      51.9 +/- 28.6/h; p < 0.001). A limitation of the study is that the mild OSA
      patients had a higher BMI when compared to the moderate to severe OSA patients.
      Ten out of 14 patients who preferred to sleep with their upper and lower dentures
      showed an increase in their AHI while wearing dentures to sleep. CONCLUSIONS:
      Contrary to previous studies, we found that OSA patients may experience more
      apneic events if they sleep with their dentures in place. Specifically, in mild
      OSAS patients, the use of dentures substantially increases the AHI especially
      when in the supine position.

PMID- 21938437
TI  - Laminin alpha5-derived peptides modulate the properties of metastatic breast
      tumour cells.
AB  - The basement membrane protein laminin-511 has been implicated in breast cancer
      progression and metastasis. To identify peptides from LM-511 that modulate the
      metastatic properties of breast tumours, we screened laminin alpha 5 chain
      derived peptides for their ability to promote adhesion of metastatic mammary
      carcinoma cells. Two selected adhesive peptides, alpha5A13b (FHVAYVLIKF) from the
      LN domain and A5G27 (RLVSYNGIIFFLK) from the LG-globular domain, were further
      characterised for their inhibitory properties against LM-511 activities in vitro
      and metastasis in vivo. In vitro, these peptides strongly inhibited LM-511
      dependent adhesion and migration of highly metastatic 4T1.2 mammary carcinoma
      cells. In addition, A5G27 but not alpha5A13b significantly reduced breast tumour
      cell proliferation and inhibited laminin-511-induced matrix metalloproteinase-9
      expression. Surprisingly, despite its potent inhibitory activity in vitro, A5G27
      promoted rather than inhibited 4T1.2 experimental pulmonary metastasis in vivo,
      regardless of its route of administration. Adhesion of 4T1.2 cells to A5G27 was
      not inhibited by antibodies directed against alpha6, beta1 or beta3 integrins or
      CD44 but was significantly reduced in the presence of heparin suggesting a role
      for cell surface glycans. Treatment of the cells with alpha-L-fucosidase but not
      neuraminidase or heparinase II also partially inhibited cell adhesion to A5G27
      and to LM-511 indicating that these interactions are mediated in part via
      terminal fucosyl residues. Overall, these results show that LMalpha5 peptides
      exhibit distinct functional properties in vitro and in vivo and suggest that
      interactions between the RLVSYNGIIFFLK sequence present in LM-511 and cell
      surface glycans may regulate LM-511 metastatic properties in vivo.

PMID- 21938438
TI  - Beta-amyloid induced changes in A-type K+ current can alter hippocampo-septal
      network dynamics.
AB  - Alzheimer's disease (AD) progression is usually associated with memory deficits
      and cognitive decline. A hallmark of AD is the accumulation of beta-amyloid
      (Abeta) peptide, which is known to affect the hippocampal pyramidal neurons in
      the early stage of AD. Previous studies have shown that Abeta can block A-type
      K(+) currents in the hippocampal pyramidal neurons and enhance the neuronal
      excitability. However, the mechanisms underlying such changes and the effects of
      the hyper-excited pyramidal neurons on the hippocampo-septal network dynamics are
      still to be investigated. In this paper, Abeta-blocked A-type current is
      simulated, and the resulting neuronal and network dynamical changes are evaluated
      in terms of the theta band power. The simulation results demonstrate an initial
      slight but significant theta band power increase as the A-type current starts to
      decrease. However, the theta band power eventually decreases as the A-type
      current is further decreased. Our analysis demonstrates that Abeta blocked A-type
      currents can increase the pyramidal neuronal excitability by preventing the
      emergence of a steady state. The increased theta band power is due to more
      pyramidal neurons recruited into spiking mode during the peak of pyramidal theta
      oscillations. However, the decreased theta band power is caused by the spiking
      phase relationship between different neuronal populations, which is critical for
      theta oscillation, is violated by the hyper-excited pyramidal neurons. Our
      findings could provide potential implications on some AD symptoms, such as memory
      deficits and AD caused epilepsy.

PMID- 21938439
TI  - Relative spike time coding and STDP-based orientation selectivity in the early
      visual system in natural continuous and saccadic vision: a computational model.
AB  - We have built a phenomenological spiking model of the cat early visual system
      comprising the retina, the Lateral Geniculate Nucleus (LGN) and V1's layer 4, and
      established four main results (1) When exposed to videos that reproduce with high
      fidelity what a cat experiences under natural conditions, adjacent Retinal
      Ganglion Cells (RGCs) have spike-time correlations at a short timescale (~30 ms),
      despite neuronal noise and possible jitter accumulation. (2) In accordance with
      recent experimental findings, the LGN filters out some noise. It thus increases
      the spike reliability and temporal precision, the sparsity, and, importantly,
      further decreases down to ~15 ms adjacent cells' correlation timescale. (3)
      Downstream simple cells in V1's layer 4, if equipped with Spike Timing-Dependent
      Plasticity (STDP), may detect these fine-scale cross-correlations, and thus
      connect principally to ON- and OFF-centre cells with Receptive Fields (RF)
      aligned in the visual space, and thereby become orientation selective, in
      accordance with Hubel and Wiesel (Journal of Physiology 160:106-154, 1962)
      classic model. Up to this point we dealt with continuous vision, and there was no
      absolute time reference such as a stimulus onset, yet information was encoded and
      decoded in the relative spike times. (4) We then simulated saccades to a static
      image and benchmarked relative spike time coding and time-to-first spike coding
      w.r.t. to saccade landing in the context of orientation representation. In both
      the retina and the LGN, relative spike times are more precise, less affected by
      pre-landing history and global contrast than absolute ones, and lead to robust
      contrast invariant orientation representations in V1.

PMID- 21938440
TI  - MRI-based motion correction of thoracic PET: initial comparison of acquisition
      protocols and correction strategies suitable for simultaneous PET/MRI systems.
AB  - OBJECTIVES: Magnetic resonance imaging (MRI) acquired on equipment capable of
      simultaneous MRI and positron emission tomography (PET) could potentially provide
      the gold standard method for motion correction of PET. To assess the latter, in
      this study we compared fast 2D and 3D MRI of the torso and used deformation
      parameters from real MRI data to correct simulated PET data for respiratory
      motion. METHODS: PET sinogram data were simulated using SimSET from a 4D pseudo
      PET image series created by segmenting MR images acquired over a respiratory
      cycle. Motion-corrected PET images were produced using post-reconstruction
      registration (PRR) and motion-compensated image reconstruction (MCIR). RESULTS:
      MRI-based motion correction improved PET image quality at the lung-liver and lung
      spleen boundaries and in the heart but little improvement was obtained where MRI
      contrast was low. The root mean square error in SUV units per voxel compared to a
      motion-free image was reduced from 0.0271 (no motion correction) to 0.0264 (PRR)
      and 0.0250 (MCIR). CONCLUSIONS: Motion correction using MRI can improve thoracic
      PET images but there are limitations due to the quality of fast MRI.

PMID- 21938441
TI  - Non-invasive assessment of functionally relevant coronary artery stenoses with
      quantitative CT perfusion: preliminary clinical experiences.
AB  - OBJECTIVES: We developed a quantitative Dynamic Contrast-Enhanced CT (DCE-CT)
      technique for measuring Myocardial Perfusion Reserve (MPR) and Volume Reserve
      (MVR) and studied their relationship with coronary stenosis. METHODS: Twenty-six
      patients with Coronary Artery Disease (CAD) were recruited. Degree of stenosis in
      each coronary artery was classified from catheter-based angiograms as Non
      Stenosed (NS, angiographically normal or mildly irregular), Moderately Stenosed
      (MS, 50-80% reduction in luminal diameter), Severely Stenosed (SS, >80%) and SS
      with Collaterals (SSC). DCE-CT at rest and after dipyridamole infusion was
      performed using 64-slice CT. Mid-diastolic heart images were corrected for beam
      hardening and analyzed using proprietary software to calculate Myocardial Blood
      Flow (MBF, in mL?min(-1)?100 g(-1)) and Blood Volume (MBV, in mL?100 g(-1))
      parametric maps. MPR and MVR in each coronary territory were calculated by
      dividing MBF and MBV after pharmacological stress by their respective baseline
      values. RESULTS: MPR and MVR in MS and SS territories were significantly lower
      than those of NS territories (p < 0.05 for all). Logistic regression analysis
      identified MPR?MVR as the best predictor of >=50% coronary lesion than MPR or MVR
      alone. CONCLUSIONS: DCE-CT imaging with quantitative CT perfusion analysis could
      be useful for detecting coronary stenoses that are functionally significant.

PMID- 21938442
TI  - Specialty-specific admission: a cost-effective intervention?
AB  - INTRODUCTION: Cost effectiveness of healthcare has become an important component
      in its delivery. Current practices need to be assessed and measured for
      variations that may lead to financial savings. Speciality specific admission is
      known not only to lead improved clinical outcomes but also to lead important cost
      reductions. METHODS: All patients admitted to an Irish teaching hospital via the
      emergency department over a 2-year period with a gastroenterology (GI) related
      illness were included in this analysis.GI illness was classified using the
      Disease related grouping (DRG) system. Mean length of stay (LOS) and patient
      level costing (PLC) were calculated. Differences between DRGs with respect to
      speciality (i.e. specialist vs. non-specialist) were calculated for the five
      commonest DRGs. RESULTS: Significant variations in LOS and PLC were demonstrated
      in the DRGs. Mean LOS varied with increasing complexity, from 3.2 days for non
      complex GI haemorrhage to 14.4 days for complex alcohol related cirrhosis as
      expected. A substantial difference in LOS within DRG groups was demonstrated by
      large standard deviations in the mean (up to 8.1 days in some groups) and was
      independent of complexity of cases. PLC also varied widely in both complex and
      non-complex cases with standard deviations of up to <euro>17,342 noted. Specialty
      specific admission was associated with shorter LOS for most GI admissions.
      CONCLUSION: Significant disparity exists for both LOS and PLC for most GI
      diagnoses. Specialty-specific admissions are associated with reduced LOS.
      Specialty-specific admission would appear to be cost-effective which may also
      lead to improved clinical outcomes.

PMID- 21938443
TI  - Antitumor bifunctional dinuclear Pt(II) complex BBR3535 forms interduplex DNA
      cross-links under molecular crowding conditions.
AB  - When antitumor platinum drugs react with DNA they form various types of
      intrastrand and interstrand cross-links (CLs). One class of new antitumor
      platinum compounds comprises bifunctional Pt(II) compounds based on the dinuclear
      or trinuclear geometry of leaving ligands. It has been shown that the DNA-binding
      modes of dinuclear or trinuclear bifunctional Pt(II) agents are distinct from
      those of mononuclear cisplatin, forming markedly more intramolecular interstrand
      CLs. However, at least two types of DNA interstrand cross-linking by bifunctional
      Pt(II) complexes can be envisaged, depending on whether the platinum complex
      coordinates to the bases in one DNA molecule (intramolecular interstrand CLs) or
      in two different DNA duplexes (interduplex CLs). We hypothesized that at least
      some antitumor bifunctional poly(di/tri)nuclear complexes could fulfill the
      requirements placed on interduplex DNA cross-linkers. To test this hypothesis we
      studied the interduplex cross-linking capability of a representative of antitumor
      polynuclear agents, namely, dinuclear Pt(II) complex [{trans-PtCl(NH(3))(2)}(2)
      MU-{trans-(H(2)N(CH(2))(6)NH(2)(CH(2))(2)NH(2)(CH(2))(6)NH(2))}](4+) (BBR3535).
      The investigations were conducted under molecular crowding conditions mimicking
      environmental conditions in the cellular nucleus, namely, in medium containing
      ethanol, which is a commonly used crowding agent. We found with the aid of native
      agarose gel electrophoresis that the DNA interduplex cross-linking efficiency of
      BBR3535 under molecular crowding conditions was remarkable: the frequency of
      these CLs was 54%. In contrast, the interduplex cross-linking efficiency of
      mononuclear cisplatin or transplatin was markedly lower (approximately 40-fold or
      18-fold, respectively). We suggest that the production of interduplex CLs in
      addition to other DNA intramolecular adducts may provide polynuclear Pt(II)
      compounds with a wider spectrum of cytotoxicity.

PMID- 21938444
TI  - Is cholecystectomy necessary after endoscopic treatment of bile duct stones in
      patients older than 80 years of age?
AB  - BACKGROUND AND AIMS: Although patients with cholecystocholedocholithiasis are
      generally referred to cholecystectomy after endoscopic sphincterotomy (ES) and
      common bile duct clearance, we often have a conflict whether cholecystectomy is
      necessary in very elderly patients with comorbid diseases. The aim of this study
      is to assess whether cholecystectomy in very elderly patients is justified after
      ES. PATIENTS AND METHODS: Patients with cholecystocholedocholithiasis who
      underwent ES and stone extraction and were followed-up for more than 10 years
      were retrospectively reviewed. We divided these patients into two groups: the
      elderly group (equal to or more than 80 years old) and young group (less than 80
      years old) and compared late biliary complications and mortality. RESULTS: The 10
      year cumulative incidence of overall biliary complications was significantly
      lower in cholecystectomized patients than in patients with gallbladder in situ in
      the young group (7.5 vs. 21.7%, p = 0.0037), but not different in the elderly
      group (8.3 vs. 7.4%, p = 0.92). When each complication was evaluated separately,
      the rate of recurrent common bile duct stones (CBDS) was not different, but that
      of acute cholecystitis was significantly lower in the elderly group than in the
      young group (4.1 vs. 22.6%, p = 0.011). CONCLUSIONS: In very elderly patients the
      incidence of acute cholecystitis is low even when the gallbladder is preserved
      after endoscopic treatment of CBDS, with a similar risk of CBDS recurrence. Thus,
      it may not be necessary to recommend cholecystectomy after ES for CBDS in very
      elderly patients.

PMID- 21938445
TI  - Follicular lymphoma with prominent fibrosis complicated by peripheral
      eosinophilia.

PMID- 21938446
TI  - Anemia and global iron fortification and supplementation.

PMID- 21938448
TI  - Nitric oxide is involved in dehydration/drought tolerance in Poncirus trifoliata
      seedlings through regulation of antioxidant systems and stomatal response.
AB  - Nitric oxide (NO) is a component of the repertoire of signals implicated in plant
      responses to environmental stimuli. In the present study, we investigated the
      effects of exogenous application of NO-releasing donor sodium nitroprusside (SNP)
      and nitric oxide synthase inhibitor N(G)-nitro-L-arginine-methyl ester (L-NAME)
      on dehydration and drought tolerance of Poncirus trifoliata. The endogenous NO
      level was enhanced by SNP pretreatment, but decreased by L-NAME, in the
      hydroponic or potted plants with or without stresses. Under dehydration, leaves
      from the SNP-treated hydroponic seedlings displayed less water loss, lower
      electrolyte leakage and reactive oxygen species accumulation, higher antioxidant
      enzyme activities and smaller stomatal apertures as compared with the control
      (treated with water). In addition, pretreatment of the potted plants with SNP
      resulted in lower electrolyte leakage, higher chlorophyll content, smaller
      stomatal conductance and larger photosynthetic rate relative to the control. By
      contrast, the inhibitor treatment changed these physiological attributes or
      phenotypes in an opposite way. These results indicate that NO in the form of SNP
      enhanced dehydration and drought tolerance, whereas the inhibitor makes the
      leaves or plants more sensitive to the stresses. The stress tolerance by NO might
      be ascribed to a combinatory effect of modulation of stomatal response and
      activation of the antioxidant enzymes. Taken together, NO is involved in
      dehydration and drought tolerance of P. trifoliata, implying that manipulation of
      this signal molecule may provide a practical approach to combat the environmental
      stresses.

PMID- 21938449
TI  - Expression of the cholera toxin B subunit (CT-B) in maize seeds and a combined
      mucosal treatment against cholera and traveler's diarrhea.
AB  - The non-toxic B subunit (CT-B) of cholera toxin from Vibrio cholerae is a strong
      immunogen and amplifies the immune reaction to conjugated antigens. In this work,
      a synthetic gene encoding for CT-B was expressed under control of a gamma-zein
      promoter in maize seeds. Levels of CT-B in maize plants were determined via
      ganglioside dependent ELISA. The highest expression level recorded in T(1)
      generation seeds was 0.0014% of total aqueous soluble protein (TASP). Expression
      level of the same event in the T(2) generation was significantly increased to
      0.0197% of TASP. Immunogenicity of maize derived CT-B was evaluated in mice with
      an oral immunization trial. Anti-CTB IgG and anti-CTB IgA were detected in the
      sera and fecal samples of the orally immunized mice, respectively. The mice were
      protected against holotoxin challenge with CT. An additional group of mice was
      administrated with an equal amount (5 MUg per dose each) of mixed maize-derived
      CT-B and LT-B (B subunit of E. coli heat labile toxin). In the sera and fecal
      samples obtained from this group, the specific antibody levels were enhanced
      compared to either the same or a higher amount of CT-B alone. These results
      suggest that a synergistic action may be achieved using a CT-B and LT-B mixture
      that can lead to a more efficacious combined vaccine to target diarrhea induced
      by both cholera and enterotoxigenic strains of Escherichia coli.

PMID- 21938450
TI  - Microvascular blood flow response in the intestinal wall and the omentum during
      negative wound pressure therapy of the open abdomen.
AB  - PURPOSE: Higher closure rates of the open abdomen have been reported with
      negative pressure wound therapy (NPWT) compared with other wound therapy
      techniques. However, the method has occasionally been associated with increased
      development of intestinal fistulae. The present study measures microvascular
      blood flow in the intestinal wall and the omentum before and during NPWT.
      METHODS: Six pigs underwent midline incision and application of NPWT to the open
      abdomen. The microvascular blood flow in the underlying intestinal loop wall and
      the omentum was recorded before and after the application of NPWT of -50, -70, 
      100, -120, -150, and -170 mmHg respectively, using laser Doppler velocimetry.
      RESULTS: A significant decrease in microvascular blood flow was seen in the
      intestinal wall during application of all negative pressures levels. The blood
      flow was 2.7 (+/-0.2) Perfusion Units (PU) before and 2.0 (+/-0.2) PU (*p < 0.05)
      after application of -50 mmHg, and 3.6 (+/-0.6) PU before and 1.5 (+/-0.2) PU
      (**p < 0.01) after application of -170 mmHg. CONCLUSIONS: In the present study,
      we show that negative pressures between -50 and -170 mmHg induce a significant
      decrease in the microvascular blood flow in the intestinal wall. The decrease in
      blood flow increased with the amount of negative pressure applied. One can only
      speculate that a longstanding decreased blood flow in the intestinal wall may
      induce ischemia and secondary necrosis in the intestinal wall, which,
      theoretically, could promote the development of intestinal fistulae. We believe
      that NPWT of the open abdomen is a very effective treatment but could probably be
      improved.

PMID- 21938451
TI  - Errors noted in: re: Migliore A, Bizzi E, Broccoli S Lagana (2011). Indirect
      comparison of etanercept, infliximab, and adalumimab for psoriatic arthritis:
      mixed treatment comparison using placebo as common comparator. Published on line
      June 21st 2011.

PMID- 21938452
TI  - Safety of immunomodulatory therapy in patients with bronchiectasis associated
      with rheumatic disease and IBD: a retrospective and cohort analysis.
AB  - Rheumatic diseases as well as inflammatory bowel disease (IBD) have been
      associated with the occurrence of non-cystic fibrosis bronchiectasis (NCFB).
      There are few data on NCFB and adverse events from immunosuppressive or
      biological response modifier therapy in patients with rheumatoid arthritis (RA)
      or IBD and NCFB. We identified 37 patients with NCFB and rheumatic disease, and
      nine patients with inflammatory bowel disease that received immunomodulatory
      treatment. We retrospectively analysed adverse pulmonary events. In nine patients
      with RA, the association between disease activity score (DAS) and spirometry was
      analysed in a small cohort study. Pulmonary side effects occurred in 50% of
      patients, most commonly respiratory infections, and resulted in a change of
      immunomodulatory treatment in 37% of patients. Spirometry and exacerbation rate
      was not different in NCFB patients with RA or IBD as compared with NFCB due to
      other causes. The incidence of pulmonary adverse events was highest in patients
      treated with conventional immunomodulatory treatment, especially methotrexate, as
      compared with patients with NCFB treated with newer biological therapies. Three
      patients were started on azithromycin because of recurrent bronchitis and had no
      events afterwards. Serial assessment of DAS and spirometry showed that a rise in
      DAS was associated with lung function decline and vice versa. Currently used
      immunosuppressive drugs can be used in NCFB albeit under close follow-up. The
      role of azithromycin for infection prevention needs further research. An
      association between DAS and lung function was shown.

PMID- 21938453
TI  - Spontaneous closure of full-thickness macular hole in type 2 idiopathic macular
      telangiectasia.

PMID- 21938454
TI  - Four cases of spinal accessory nerve passing through the fenestrated internal
      jugular vein.
AB  - PURPOSE: Neck dissection (ND) is an important technique for the treatment of
      cervical lymph node metastasis in patients with head and neck cancer. Since the
      introduction of functional ND (FND), various modifications have been made to
      reduce the adverse effects of radical ND. Recently, many investigators have
      documented cases of FND with preservation of the spinal accessory nerve (SAN)
      and/or the sternocleidomastoid muscle, which have contributed to improve the
      quality of life following ND. For this type of ND, special attention must be paid
      to identify the SAN and the internal jugular vein (IJV). METHODS: We performed
      123 NDs over 2 years at the Department of Otolaryngology, Head and Neck Surgery,
      Kobe University Hospital. We collected data of all patients who underwent NDs by
      retrospectively reviewing the relevant hospital medical records and operative
      notes. RESULTS: In 4 out of 123 NDs (3.3%), an anomaly of the SAN passing through
      the fenestrated IJV was observed. CONCLUSION: Although this anomaly is rare, head
      and neck surgeons should be aware of this anomalous relationship between the SAN
      and the IJV in order to avoid accidental injury to these structures during ND.

PMID- 21938455
TI  - Structural insights into human GPCR protein OA1: a computational perspective.
AB  - Human ocular albinism type 1 protein (OA1)-a member of the G-protein coupled
      receptor (GPCR) superfamily-is an integral membrane glycoprotein expressed
      exclusively by intracellular organelles known as melanocytes, and is responsible
      for the proper biogenesis of melanosomes. Mutations in the Oa1 gene are
      responsible for the disease ocular albinism. Despite its clinical importance,
      there is a lack of in-depth understanding of its structure and mechanism of
      activation due to the absence of a crystal structure. In the present study,
      homology modeling was applied to predicting OA1 structure following thorough
      sequence analysis and secondary structure predictions. The predicted model had
      the signature residues and motifs expected of GPCRs, and was used for carrying
      out molecular docking studies with an endogenous ligand, L-DOPA and an
      antagonist, dopamine; the results agreed quite well with the available
      experimental data. Finally, three sets of explicit molecular dynamics simulations
      were carried out in lipid bilayer, the results of which not only confirmed the
      stability of the predicted model, but also helped witness some differences in
      structural features such as rotamer toggle switch, helical tilts and hydrogen
      bonding pattern that helped distinguish between the agonist- and antagonist-bound
      receptor forms. In place of the typical "D/ERY"-motif-mediated "ionic lock", a
      hydrogen bond mediated by the "DAY" motif was observed that could be used to
      distinguish the agonist and antagonist bound forms of OA1. In the absence of a
      crystal structure, this study helped to shed some light on the structural
      features of OA1, and its behavior in the presence of an agonist and an
      antagonist, which might be helpful in the future drug discovery process for
      ocular albinism.

PMID- 21938456
TI  - Hemodynamic collapse following bilateral knee arthroplasty: a mysterious case.
AB  - Severe hemodynamic collapse after knee surgery from bilateral adrenal hemorrhages
      is rare. Even rarer is it occurring from adrenal hemorrhage as a complication of
      heparin induced thrombocytopenia. Due to lack of awareness of this rare
      complication and associated complex scenario in critically ill patients,
      diagnosis is often made post mortem. A diagnosis of bilateral adrenal hemorrhage
      should be considered in any patient presenting with non-specific symptoms of
      fever, abdominal pain, confusion and rapid hemodynamic collapse not responding to
      standard therapy. This is crucial especially in the setting of heparin induced
      thrombocytopenia as thrombosis and not hemorrhage is often the most feared
      complication of this syndrome.

PMID- 21938457
TI  - Chronic migraine plus medication overuse headache: two entities or not?
AB  - Chronic migraine (CM) represents migraine natural evolution from its episodic
      form. It is realized through a chronicization phase that may require months or
      years and varies from patient to patient. The transition to more frequent attacks
      pattern is influenced by lifestyle, life events, comorbid conditions and personal
      genetic terrain, and it often leads to acute drugs overuse. Medication overuse
      headache (MOH) may complicate every type of headache and all the drugs employed
      for headache treatment can cause MOH. The first step in the management of CM
      complicated by medication overuse must be the withdrawal of the overused drugs
      and a detoxification treatment. The goal is not only to detoxify the patient and
      stop the chronic headache but also to improve responsiveness to acute or
      prophylactic drugs. Different methods have been suggested: gradual or abrupt
      withdrawal; home treatment, hospitalization, or a day-hospital setting; re
      prophylaxes performed immediately or at the end of the wash-out period. Up to
      now, only topiramate and local injection of onabotulinumtoxinA have shown
      efficacy as therapeutic agents for re-prophylaxis after detoxification in
      patients with CM with and without medication overuse. Although the two treatments
      showed similar efficacy, onabotulinumtoxinA is associated with a better adverse
      events profile. Recently, the Phase III Research Evaluating Migraine Prophylaxis
      Therapy (PREEMPT) clinical program proved that patients with CM, even those with
      MOH, are the ones most likely to benefit from onabotulinumtoxinA treatment.
      Furthermore, it provided an injection paradigm that can be used as a guide for a
      correct administration of onabotulinumtoxinA.

PMID- 21938458
TI  - Expression of the nos operon proteins from Pseudomonas stutzeri in transgenic
      plants to assemble nitrous oxide reductase.
AB  - Nitrous oxide (N(2)O) is a stable greenhouse gas that plays a significant role in
      the destruction of the ozone layer. Soils are a significant source of atmospheric
      N(2)O. It is important to explore some innovative and effective biology-based
      strategies for N(2)O mitigation. The enzyme nitrous oxide reductase (N(2)OR),
      naturally found in soil bacteria, is responsible for catalysing the final step of
      the denitrification pathway, conversion of N(2)O to dintrogen gas (N(2)). To
      transfer this catalytic pathway from soil into plants and amplify the abundance
      of this essential mechanism (to reduce global warming), a mega-cassette of five
      coding sequences was assembled to produce transgenic plants heterologously
      expressing the bacterial nos operon in plant leaves. Both the single-gene
      transformants (nosZ) and the multi-gene transformants (nosFLZDY) produced active
      recombinant N(2)OR. Enzymatic activity was detected using the methyl viologen
      linked enzyme assay, showing that extracts from both types of transgenic plants
      exhibited N(2)O-reducing activity. Remarkably, the single-gene strategy produced
      higher reductase capability than the whole-operon approach. The data indicate
      that bacterial N(2)OR expressed in plants could convert N(2)O into inert N(2)
      without involvement of other Nos proteins. Silencing by homologous signal
      sequences, or cryptic intracellular targeting are possible explanations for the
      low activities obtained. Expressing N(2)OR from Pseudomonas stutzeri in single
      gene transgenic plants indicated that such ag-biotech solutions to climate change
      have the potential to be easily incorporated into existing genetically modified
      organism seed germplasm.

PMID- 21938462
TI  - Molecular characterization of allium virus X, a new potexvirus in the family
      Alphaflexiviridae, infecting ornamental allium.
AB  - ABTRACT: A new potexvirus affecting ornamental allium spp in the Netherlands was
      identified and characterized at the molecular level. The virus had a single
      stranded RNA genome of 7100 bp (excluding the 18 bp poly A tail). The genome
      organization was found to be typical of members of the genus Potexvirus and
      consisted of five open reading frames (ORF). Nucleotide and amino acid sequence
      comparisons with those of known potexvirus members showed that this virus is
      related to Hosta virus X and Hydrangea ringspot virus. Sequence similarities and
      phylogenetic relationships suggested that the allium virus is a new and distinct
      species in the genus Potexvirus and the name, Allium virus X (AlVX) is proposed.

PMID- 21938461
TI  - Solitary fibrous tumor of the central nervous system: a clinicopathologic study
      of 24 cases.
AB  - OBJECTIVE: Solitary fibrous tumor is a rare, spindle-cell benign mesenchymal
      neoplasm and has a high recurrence rate. In this study, we reviewed our
      experience in the diagnosis and treatment of 24 patients with central nervous
      system solitary fibrous tumors. METHODS: Clinical data were retrieved from the
      medical records. Prognosis was assessed by clinic service and telephone
      interview. The specimens were stained with hematoxylin and eosin.
      Immunohistochemistry for CD34, CD99, EMA, HMB-45, Bcl-2, vimentin, GFAP, S-100,
      MBP, CK and MIB-1 was performed in all cases. Distributions of time to
      progression and recurrence were estimated using the Kaplan-Meier method and
      compared using the log-rank test. RESULTS: The 24 patients included 13 men and 11
      women with a median age of 49.0 years. The most frequent initial symptoms were
      headache, dizziness, unstable walk and hearing loss. The most common location was
      cerebellar pontine angle (n = 6). Surgery reached gross total removal for 18
      patients but subtotal removal for six patients on initial operation.
      Histopathologic examination showed spindle to oval cells were disposed in wavy
      fascicles between prominent, eosinophilic bands of collagen. Dense bands of
      collagen appeared in cross section as minute nodules that separated individual
      tumor cells. Cellular areas with a partial hemangiopericytoma pattern were noted
      in six cases. Atypical presentations were shown on initial operation in three
      cases. CD34, CD99 and vimentin were 100% positive; but EMA, CK, MBP, HBM-45 and
      GRAP were 100% negative. The positive in Bcl-2, RF and S-100 was 89%, 85% and
      26%, respectively. Follow-up information was available for 23 patients. The
      median follow-up period was 36.0 months. Nine patients recurred and one patient
      died from the progression. Incomplete surgical resection was significantly
      associated with recurrence (p = 0.010). MIB-1 labeling index in recurrence was
      higher than in no recurrence (6.0% versus 3.4%, p = 0.029). All treated with
      subtotal removal only had subsequent tumor recurrence or progression; however,
      the two patients who were administered adjuvant radiosurgery after subtotal
      removal did not recur or progress. Adjuvant radiosurgery seemed to improve the
      prognosis (p = 0.028). CONCLUSIONS: Solitary fibrous tumor is a rare mesenchymal
      tumor with a propensity to recur. The most affected area is the cerebellopontine
      angle. Immunohistochemistry should be used to differentiate solitary fibrous
      tumor from other tumors. The extent of resection, MIB-1 labeling index and some
      anaplastic features might be predictive for recurrence. Postoperative
      radiosurgery might be an option in incompletely resected solitary fibrous tumor.
      Regular and long-term follow-up remains mandatory to monitor recurrence.

PMID- 21938463
TI  - UL74 of human cytomegalovirus reduces the inhibitory effect of gH-specific and gB
      specific antibodies.
AB  - The human cytomegalovirus (HCMV) glycoproteins gH (UL75) and gL (UL115) can form
      complexes with gO (UL74) or with proteins of the UL128-UL131A locus. Deletion of
      gO abolishes cell-free virus transmission and renders cell-associated virus
      transmission in fibroblasts more sensitive to inhibition by human anti-HCMV
      serum. To test whether the latter effect is specific for gO, we compared mutants
      with deletions in UL74, UL99 and the UL128-131A locus regarding their sensitivity
      to anti-HCMV antibodies. UL74 deletion mutants were more sensitive to a further
      restriction by polyspecific or gH-specific antibodies than control mutants,
      showing that gO specifically protects focal growth against inhibitory antibodies.
      This effect was not confined to gH-specific antibodies, as UL74 deletion mutants
      were also inhibited by an anti-gB antibody. In conclusion, gO specifically
      promotes focal spread in the presence of gH and gB antibodies, thus contributing
      to the ability of HCMV to resist the host's immune response.

PMID- 21938464
TI  - Investigation into the anti-inflammatory and antigranuloma activity of Colchicum
      luteum Baker in experimental models.
AB  - The present study evaluates the anti-inflammatory and antigranuloma activity of
      CLHE in experimental models, viz. carrageenan-induced paw edema, subcutaneous
      cotton pellet implantation-induced granuloma formation, and complete Freund's
      adjuvant-induced stimulation of peritoneal macrophages in rats. Serum TNF-alpha,
      IL-6, and IL-1 beta levels were estimated as markers for global effects of
      inflammation. TNF-R1 protein expression was estimated in stimulated peritoneal
      macrophages. There was a significant reduction (P < 0.05) of paw edema in the
      CLHE-treated groups as compared to control. In the cotton pellet-induced
      granuloma model, there was a significant (P < 0.05) reduction in the dry
      granuloma weight and serum TNF-alpha, IL-6, and IL-1beta levels in the CLHE
      treated group as compared to control. Immunoblot analysis for TNF-R1 also
      demonstrated a significant reduction in the receptor protein expression on
      stimulated macrophages. Result of the present study thus demonstrates and
      validates the antigranuloma activity of CLHE.

PMID- 21938465
TI  - Measurement of cerebral circulation times using dynamic whole-brain CT
      angiography: feasibility and initial experience.
AB  - The objective of the study was to use 320-detector row 4D CT angiography (CTA)
      for measuring cerebral circulation times (CCT) and to assess early venous
      drainage (EVD) and shortening of CCT in arteriovenous malformations (AVM) and to
      compare with DSA. CCT of 12 physiological patients and five AVM patients were
      acquired using a 4D CTA protocol by recording cerebrovascular bolus passage time.
      In the AVM patients EVD time (EVDT) was measured. Identical measurements were
      performed on DSA for the AVM patients. It was found that the physiological CCTs
      were 5.8 +/- 1.4 s (M +/- SD). EVD was seen in all AVMs and resulted in a
      shortened CCT of 3.4 +/- 1.1 s (p = 0.01). There was no significant difference
      for CCT and EVDT values derived from DSA and 4D CTA. Thus, the CCTs can be
      measured non-invasively using clinical 4D CTA. Early venous drainage with
      shortened CCTs was observed by 4D CTA in all five patients with AVMs.

PMID- 21938466
TI  - Pontine hemorrhage at a microbleed site in a patient with central pontine
      myelinolysis.

PMID- 21938467
TI  - Species identification and authentification of human and rodent cell cultures
      using polymerase chain reaction analysis of vomeronasal receptor genes.
AB  - Cell culture and the use of cell lines are routinely used in basic scientific
      research. It is therefore imperative for researchers to ensure the origin of the
      cell lines used and that they are routinely re-analysed for contamination and
      misidentification. Inter-species contamination is relatively frequent, and the
      most commonly used cell lines are of human, mouse and rat derivation. We have
      developed simple species specific primer assays based on genomic sequence
      differences in vomeronasal receptor gene family members to discriminate between
      human, mouse and rat DNA using standard agarose gel electrophoresis. Furthermore,
      these PCR assays are able to identify the species composition within an inter
      species mixed population. This approach therefore provides a valuable tool to
      enable a rapid, simple and relatively inexpensive determination of the
      authentication and contamination of cell cultures.

PMID- 21938468
TI  - Clinical reagents of GM-CSF and IFN-alpha induce the generation of functional
      chronic myeloid leukemia dendritic cells in vitro.
AB  - Dendritic cells (DCs) have been successfully induced in vitro from chronic
      myeloid leukemia (CML) cells, which may provide a promising immunotherapeutic
      protocol for CML. To facilitate the optimization of DCs-based vaccination
      protocols, we investigated the efficiency of in vitro generation of DCs from bone
      marrow mononuclear cells of CML patients by clinical reagents of GM-CSF and IFN
      alpha. Bone marrow mononuclear cells were isolated from eight CML patients and
      CML-DCs were generated in the presence of different cytokines (Group A: GM-CSF
      for research and IL-4 for research; Group B: GM-CSF for injection and IFN-alpha
      for injection) in RMPI-1640 medium containing 10% human AB serum. After 8 days,
      the morphologic features of CML-DCs were observed and their immunophenotypes were
      analyzed by flow cytometry. The activity of CML-DCs was determined by evaluating
      their ability to stimulate allogeneic mixed lymphocyte reaction (allo-MLR) and
      anti-leukemic cytotoxic T lymphocytes (CTLs). The culture protocols were
      successful in generating functional CML-DCs from all the CML patients as
      evidenced by the significant upregulation of CD80, CD86, CD83 HLA-DR and CD1a
      compared to pre-cultured (p < 0.05), and increased allogeneic T cell stimulating
      proliferation capacity (p < 0.05). CML-DCs could stimulate a specific anti
      leukemia response. In summary, we demonstrate that the combination of clinical
      reagents GM-CSF and IFN-alpha induced the generation of DCs that have the ability
      to stimulate a specific anti-leukemia CTLs response in vitro, indicating their
      feasibility for clinical vaccination protocols for CML patients.

PMID- 21938469
TI  - Anti-proliferative and pro-apoptotic effect of carvacrol on human hepatocellular
      carcinoma cell line HepG-2.
AB  - Carvacrol is one of the members of monoterpene phenol and is present in the
      volatile oils of Thymus vulgaris, Carum copticum, origanum and oregano. It is a
      safe food additive commonly used in our daily life, and few studies have
      indicated that carvacrol has anti-hepatocarcinogenic activities. The rationale of
      the study was to examine whether carvacrol affects apoptosis of human hepatoma
      HepG2 cells. In this study, we showed that carvacrol inhibited HepG2 cell growth 
      by inducing apoptosis as evidenced by Hoechst 33258 stain and Flow cytometric
      (FCM) analysis. Incubation of HepG2 cells with carvacrol for 24 h induced
      apoptosis by the activation of caspase-3, cleavage of PARP and decreased Bcl-2
      gene expression. These results demonstrated that a significant fraction of
      carvacrol treated cells died by an apoptotic pathway in HepG2 cells. Moreover,
      carvacrol selectively altered the phosphorylation state of members of the MAPK
      superfamily, decreasing phosphorylation of ERK1/2 significantly in a dose
      dependent manner, and activated phosphorylation of p38 but not affecting JNK MAPK
      phosphorylation. These results suggest that carvacrol may induce apoptosis by
      direct activation of the mitochondrial pathway, and the mitogen-activated protein
      kinase pathway may play an important role in the antitumor effect of carvacrol.
      These results have identified, for the first time, the biological activity of
      carvacrol in HepG2 cells and should lead to further development of carvacrol for
      liver disease therapy.

PMID- 21938470
TI  - Eicosapentaenoic acid protects against 2,3,7,8-tetrachlorodibenzo-p-dioxin
      induced hepatic toxicity in cultured rat hepatocytes.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent and ubiquitous
      environmental contaminant. The health impact of TCDD exposure is of great concern
      to the general public. Recent reports have implied that eicosapentaenoic acid
      (EPA) might be a potential chemopreventive agent and influence hepatotoxicity.
      The aim of the current study was to explore the effectiveness of EPA in
      alleviating the toxicity of TCDD on primary cultured rat hepatocytes. EPA (5, 10
      and 20 MUM) was added to cultures alone or simultaneously with TCDD (5 and 10
      MUM). Rat hepatocytes were treated with TCDD and EPA for 48 h, and then
      cytotoxicity was detected by [3-(4,5-dimethyl-thiazol-2-yl) 2,5
      diphenyltetrazolium bromide] (MTT) assay and lactate dehydrogenase (LDH) release,
      while total antioxidant capacity (TAC) and total oxidative stress (TOS) levels
      were determined to evaluate the oxidative injury. The DNA damage was also
      analyzed by liver micronucleus assay (LMN) and 8-oxo-2-deoxyguanosine (8-OH-dG).
      The results of MTT and LDH assays showed that TCDD but not EPA decreased cell
      viability. TCDD also increased TOS level and significantly decreased TAC level in
      rat hepatocytes in a clear dose dependent manner. On the basis of increasing
      doses, the dioxin caused significant increases of micronucleated hepatocytes
      (MNHEPs) and 8-OH-dG as compared to control culture. Whereas, in cultures treated
      with EPA alone, TOS level did not change and the level of TAC significantly
      increased. The presence of EPA with TCDD minimized the toxic effects of the
      dioxin on primary hepatocytes cultures. Noteworthy, EPA has a protective effect
      against TCDD-mediated DNA damages.

PMID- 21938471
TI  - Risk factors for the development of stress urinary incontinence in women.
AB  - Large-scale population-based surveys published in the past decade give new
      insights regarding risk factors for stress urinary incontinence (SUI) in women.
      Age plays a significant role in the development of all forms of urinary
      incontinence, but findings regarding the role of hormonal changes are
      inconsistent. Obesity is an increasingly prevalent health condition that was
      shown to have detrimental impact on SUI development, while weight reduction was
      proven to reduce SUI. Other modifiable risk factors, such as diabetes, also are
      related to SUI. Pregnancy, delivery, and pelvic floor surgery are risk factors
      discussed in the review. Recent genetic studies identified several genes encoding
      components of the extracellular matrix, which could be related to a
      predisposition to SUI. Identifying risk factors for SUI can facilitate prevention
      strategies in an aim to reduce SUI prevalence among women.

PMID- 21938472
TI  - A second 'overexpression' allele at the Glu-B1 high-molecular-weight glutenin
      locus of wheat: sequence characterisation and functional effects.
AB  - Bread is one of the major constituents of the human diet and wheat (Triticum
      aestivum L.) is the most important cereal for bread making. The gluten proteins
      (glutenins and gliadins) are recognised as important components affecting the
      processing quality of wheat flour. In this research, we investigated a particular
      glutenin subunit allele in an Australian cultivar, H45. Based on protein and DNA
      assays, the Glu-B1 allele of H45 seems to be Glu-B1al, an allele that includes a
      functional duplication of a gene encoding an x-type high-molecular-weight
      glutenin subunit, and is thought to increase dough strength through
      overexpression of that subunit. Yet H45 does not have the dough properties that
      would be expected if it carries the Glu-B1al allele. After confirming that H45
      overexpresses Bx subunits and that it has relatively low un-extractable polymeric
      protein (an indicator of weak dough), we cloned and sequenced two Bx genes from
      H45. The sequences of the two genes differ from each other, and they each differ
      by four single-nucleotide polymorphisms (SNPs) from the sequence that has been
      reported for the Glu-B1al x-type glutenin genes of the Canadian wheat cultivar
      Glenlea. One of the SNPs leads to an extra cysteine residue in one of the
      subunits. The presence of this additional cysteine may explain the dough
      properties of H45 through effects on cross-linkage within or between glutenin
      subunits. We propose that the Glu-B1 allele of H45 be designated Glu-B1br, and we
      present evidence that Glu-B1br is co-inherited with low un-extractable polymeric
      protein.

PMID- 21938473
TI  - A QTL for rice grain yield in aerobic environments with large effects in three
      genetic backgrounds.
AB  - A large-effect QTL associated with grain yield in aerobic environments was
      identified in three genetic backgrounds, Apo/(2)*Swarna, Apo/(2)*IR72, and
      Vandana/(2)*IR72, using bulk-segregant analysis (BSA). Apo and Vandana are
      drought-tolerant aerobic-adapted varieties, while Swarna and IR72 are important
      lowland rice varieties grown on millions of hectares in Asia but perform poorly
      in aerobic conditions. Two closely linked rice microsatellite (RM) markers, RM510
      and RM19367, located on chromosome 6, were found to be associated with yield
      under aerobic soil conditions in all three backgrounds. The QTL linked to this
      marker, qDTY6.1 (DTY, grain yield under drought), was mapped to a 2.2 cM region
      between RM19367 and RM3805 at a peak LOD score of 32 in the Apo/(2)*Swarna
      population. The effect of qDTY6.1 was tested in a total of 20 hydrological
      environments over a period of five seasons and in five populations in the three
      genetic backgrounds. In the Apo/(2)*Swarna population, qDTY6.1 had a large effect
      on grain yield under favorable aerobic (R (2) <= 66%) and irrigated lowland (R
      (2) < 39%) conditions but not under drought stress; Apo contributed the favorable
      allele in all the conditions where an effect was observed. In the Apo/IR72 cross,
      Apo contributed the favorable allele in almost all the aerobic environments in
      RIL and BC(1)-derived populations. In the Vandana/IR72 RIL and BC(1)-derived
      populations, qDTY6.1 had a strong effect on yield in aerobic drought stress,
      aerobic non-stress, and irrigated lowland conditions; the Vandana allele was
      favorable in aerobic environments and the IR72 allele was favorable in irrigated
      lowland environments. We conclude that qDTY6.1 is a large-effect QTL for rice
      grain yield under aerobic environments and could potentially be used in molecular
      breeding of rice for aerobic environments.

PMID- 21938474
TI  - Evaluation of genome-wide selection efficiency in maize nested association
      mapping populations.
AB  - In comparison to conventional marker-assisted selection (MAS), which utilizes
      only a subset of genetic markers associated with a trait to predict breeding
      values (BVs), genome-wide selection (GWS) improves prediction accuracies by
      incorporating all markers into a model simultaneously. This strategy avoids risks
      of missing quantitative trait loci (QTL) with small effects. Here, we evaluated
      the accuracy of prediction for three corn flowering traits days to silking, days
      to anthesis, and anthesis-silking interval with GWS based on cross-validation
      experiments using a large data set of 25 nested association mapping populations
      in maize (Zea mays). We found that GWS via ridge regression-best linear unbiased
      prediction (RR-BLUP) gave significantly higher predictions compared to MAS
      utilizing composite interval mapping (CIM). The CIM method may be selected over
      multiple linear regression to decrease over-estimations of the efficiency of GWS
      over a MAS strategy. The RR-BLUP method was the preferred method for estimating
      marker effects in GWS with prediction accuracies comparable to or greater than
      BayesA and BayesB. The accuracy with RR-BLUP increased with training sample
      proportion, marker density, and heritability until it reached a plateau. In
      general, gains in accuracy with RR-BLUP over CIM increased with decreases of
      these factors. Compared to training sample proportion, the accuracy of prediction
      with RR-BLUP was relatively insensitive to marker density.

PMID- 21938475
TI  - QTL for nodal root angle in sorghum (Sorghum bicolor L. Moench) co-locate with
      QTL for traits associated with drought adaptation.
AB  - Nodal root angle in sorghum influences vertical and horizontal root distribution
      in the soil profile and is thus relevant to drought adaptation. In this study, we
      report for the first time on the mapping of four QTL for nodal root angle (qRA)
      in sorghum, in addition to three QTL for root dry weight, two for shoot dry
      weight, and three for plant leaf area. Phenotyping was done at the six leaf stage
      for a mapping population (n = 141) developed by crossing two inbred sorghum lines
      with contrasting root angle. Nodal root angle QTL explained 58.2% of the
      phenotypic variance and were validated across a range of diverse inbred lines.
      Three of the four nodal root angle QTL showed homology to previously identified
      root angle QTL in rice and maize, whereas all four QTL co-located with previously
      identified QTL for stay-green in sorghum. A putative association between nodal
      root angle QTL and grain yield was identified through single marker analysis on
      field testing data from a subset of the mapping population grown in hybrid
      combination with three different tester lines. Furthermore, a putative
      association between nodal root angle QTL and stay-green was identified using data
      sets from selected sorghum nested association mapping populations segregating for
      root angle. The identification of nodal root angle QTL presents new opportunities
      for improving drought adaptation mechanisms via molecular breeding to manipulate
      a trait for which selection has previously been very difficult.

PMID- 21938476
TI  - Ras signaling in NGF reduction and TNF-alpha-related pancreatic beta cell
      apoptosis in hyperglycemic rats.
AB  - Recent evidence suggested that tumor necrosis factor-alpha (TNF-alpha) and nerve
      growth factor (NGF) withdrawal activated a common apoptotic pathway. Here, we
      aimed to investigate the possible role of apoptotic Ras effectors RASSF1 and
      NORE1 in NGF reduction and TNF-alpha-related beta cell apoptosis in
      streptozotocin (STZ)-induced hyperglycemic rats. Rats were divided into four
      groups: the first group was given saline and citrate buffer, the second group was
      injected 4-methylcatechol (4-MC), an inducer of NGF synthesis, the third group
      received STZ, and the fourth group was given both 4-MC and STZ. 4-MC (10 MUg/kg)
      was administered by daily intraperitoneal injection for 10 days before the
      animals were rendered hyperglycemic by administration of single dose STZ (75
      mg/kg). With 4-MC pretreatment to hyperglycemic rats the following results were
      noted: (i) Decrease in pancreatic NGF level was blocked, (ii) Increase in
      pancreatic TNF-alpha level and the number of TNF-alpha(+) beta cell in the islets
      were prevented, (iii) Increase in the number of beta cell synthhesized apoptotic
      Ras effectors that RASSF1 and NORE1 was blocked, (iv) While pancreatic lipid
      peroxidation level decreased, antioxidant molecule glutathione and antioxidant
      enzymes glutathione peroxidase, catalase and superoxide dismutase activities
      increased, (v) Pancreatic caspase-3 activity and the number of cleaved caspase
      3(+) beta cells were decreased. These results strengthen the idea that TNF-alpha
      and reduction in NGF can activate a common apoptotic pathway. Moreover, these
      data display that new apoptotic Ras effector molecules RASSF1 and NORE1 play
      important role with oxidative stress in NGF reduction and TNF-alpha-related
      pancreatic beta cell apoptosis in hyperglycemic rats. Furthermore, these findings
      suggest that 4-MC can prevent beta cell apoptosis possibly through increasing NGF
      synthesis in hyperglycemic rats.

PMID- 21938477
TI  - Inhibition of deoxycholate-induced apoptosis in iron-depleted HCT-116 cells.
AB  - The bile acid, deoxycholate (DOC), can induce apoptosis in cells containing
      adequate amounts of all key nutrients, but it is unknown whether DOC-induced
      apoptosis can occur in cells lacking a single key nutrient. The aim of this study
      was to determine if DOC is able to induce apoptosis in HCT-116 colon epithelial
      cells depleted of iron. The cells were made iron-deficient by pre-treating them
      with the iron chelator, deferoxamine (DFO), before subsequent exposure to DOC.
      Mitochondrial dysfunction was detected in control cells exposed to DOC, but not
      in iron-depleted cells exposed to DOC. Moreover, characteristic features of
      apoptosis, namely, membrane blebbing, formation of apoptotic bodies, cytochrome c
      release into cytosol, generation of the activated form of caspase-3, chromatin
      condensation and fragmentation, and also plasma membrane phospholipid
      translocation, were all induced by DOC in control cells but not in iron-depleted
      cells. Treating DFO-pretreated cells with ferrous sulfate to replenish cellular
      iron restored the ability of DOC to induce apoptosis. In relating these findings
      to oxidative stress, it was found that DOC also induced the formation of reactive
      oxygen species and caused DNA damage in control cells, but not in iron-depleted
      cells. Collectively, the results suggest that in order for HCT-116 cells to
      undergo apoptosis when exposed to DOC, adequate amounts of intracellular iron
      must be present.

PMID- 21938478
TI  - Diabetes mellitus and incidence and mortality of colorectal cancer: a systematic
      review and meta-analysis of cohort studies.
AB  - Increasing evidence suggests that a history of diabetes mellitus (DM) may be
      associated with an increased risk of colorectal cancer (CRC). To provide a
      quantitative assessment of the association between DM and risk of CRC, We
      evaluated the relation between DM and incidence and mortality of CRC in a
      systematic review of cohort studies. Full publications of cohort studies were
      identified in MEDLINE, EMBASE and Science Citation Index Expanded, through
      February 28, 2011. Summary relative risks (SRRs) with 95% confidence intervals
      (CIs) were summarized using a random-effects model. Between-study heterogeneity
      was assessed using the Cochran's Q and I2 statistics. A total of 41 cohort
      studies (35 articles) were included in this systematic review. Combining 30
      cohort studies which presented results on diabetes and CRC incidence, diabetes
      was associated with an increased incidence of CRC (SRRs 1.27, 95% CI: 1.21-1.34),
      with evident heterogeneity among studies (P=0.002, I2=48.4%). Subgroup analysis
      and meta-regression analysis by controlling the confounders showed that the
      increased incidence of CRC was independent of geographic locations, sex, family
      history of colorectal cancer, smoking, physical activity and body mass index.
      Diabetes was also positively associated with CRC mortality (SRR 1.20, 95% CI:
      1.03-1.40), with evidence of heterogeneity between studies (P<0.001, I2=81.4%).
      Results from this systematic review support that compared to non-diabetic
      individuals, diabetic individuals have an increased risk of CRC.

PMID- 21938479
TI  - Influence of endogenous opioid systems on T lymphocytes as assessed by the
      knockout of mu, delta and kappa opioid receptors.
AB  - Here, we evaluated the influence of endogenous opioid activation on immune
      responses by examining consequences of all three opioid receptor gene (mu, delta
      and kappa) inactivation. In triple-opioid receptor knockout mice, splenocytes and
      thymocytes numbers, lymphocyte subsets as well as proliferation and cytokines
      induced by in vitro stimulation of T lymphocytes were measured. Compared with
      wild-type mice, similar lymphocyte distribution in thymus and spleen as well as
      comparable T lymphocyte proliferation were observed, while lower levels of IL-2
      and IFNgamma as well as higher levels of IL-4 and IL-10 were found in triple
      opioid receptor knockout mice. Together, our results indicate a shift from TH1 to
      TH2 cytokines in triple-opioid receptor knockout animals, suggesting that global
      endogenous opioid tone drives T lymphocytes toward a TH1 profile under non
      pathological conditions.

PMID- 21938480
TI  - Taking the heat: thermoregulation in Asian elephants under different climatic
      conditions.
AB  - Some mammals indigenous to desert environments, such as camels, cope with high
      heat load by tolerating an increase in body temperature (T (b)) during the hot
      day, and by dissipating excess heat during the cooler night hours, i.e.,
      heterothermy. Because diurnal heat storage mechanisms should be favoured by large
      body size, we investigated whether this response also exists in Asian elephants
      when exposed to warm environmental conditions of their natural habitat. We
      compared daily cycles of intestinal T (b) of 11 adult Asian elephants living
      under natural ambient temperatures (T (a)) in Thailand (mean T (a) ~ 30 degrees
      C) and in 6 Asian elephants exposed to cooler conditions (mean T (a) ~ 21 degrees
      C) in Germany. Elephants in Thailand had mean daily ranges of T (b) oscillations
      (1.15 degrees C) that were significantly larger than in animals kept in Germany
      (0.51 degrees C). This was due to both increased maximum T (b) during the day and
      decreased minimum T (b) at late night. Elephant's minimum T (b) lowered daily as
      T (a) increased and hence entered the day with a thermal reserve for additional
      heat storage, very similar to arid-zone ungulates. We conclude that these
      responses show all characteristics of heterothermy, and that this
      thermoregulatory strategy is not restricted to desert mammals, but is also
      employed by Asian elephants.

PMID- 21938481
TI  - Bisphosphonates modulate the expression of OPG and M-CSF in hMSC-derived
      osteoblasts.
AB  - Bisphosphonates have been known to suppress osteoclast activity, survival, and
      recruitment. In this study, we tested effects of BPs on expression of two
      critical genes for osteoclastogenesis, M-CSF, and OPG in the process of
      osteoblast differentiation from hMSC. (1) The cells were cultured in osteogenic
      induction medium together with 0 (control group) and 10-8 M alendronate,
      pamidronate for up 2 and 3 weeks (for real-time PCR) and 3 and 4 weeks (for
      ELISA). (2) The real-time PCR protocol for M-CSF, OPG, and glyceraldehyde 3
      phosphate dehydrogenase (GAPDH) consist of 40 cycles. (3) Enzyme-linked
      immunosorbent assay (ELISA): the amounts of M-CSF and OPG in the culture medium
      were determined using commercially available ELISA kits for M-CSF and OPG.
      Treatment of differentiating cells with alendronate or pamidronate, nitrogen
      containing BPs increase the expression of OPG, which suppresses
      osteoclastogenesis, whereas it decreases the expression of M-CSF, which enhances
      preosteoclast formation. These results suggest a new mechanism by which BPs
      inhibit osteoclastogenesis. Results support hypothesis that progressive
      accumulation of bisphosphonate in jaws causes imbalance in osteogenesis and bone
      absorption and collateral osteoclast-osteoblast interaction. Bisphosphonate
      related osteonecrosis of jaw (BPONJ) is one of the most serious complications of
      bisphosphonate (BP) therapy. However, the mechanism behind the this process of
      BPONJ is still unclear and there are so many hypotheses. Among many hypotheses,
      we focused on osteoclast-osteoblast interaction in this study. The findings of
      this study show new light on the present BPONJ occurrence theory based on the
      osteoclastic activity of BPs. Also, a more advanced and developed theory for
      BRONJ occurrence may be obtained by combining the osteoclast inhibition mechanism
      and the effects on osteoblastic differentiation by BPs.

PMID- 21938482
TI  - Recombinant human endostatin endostar inhibits tumor growth and metastasis in a
      mouse xenograft model of colon cancer.
AB  - To investigate the effects of recombinant human endostatin Endostar on metastasis
      and angiogenesis and lymphangiogenesis of colorectal cancer cells in a mouse
      xenograft model. Colon cancer cells SW620 were injected subcutaneously into the
      left hind flank of nude mice to establish mouse xenograft models. The mice were
      treated with normal saline or Endostar subcutaneously every other day. The growth
      and lymph node metastasis of tumor cells, angiogenesis and lymphangiogenesis in
      tumor tissue were detected. Apoptosis and cell cycle distribution were studied by
      flow cytometry. The expression of VEGF-A, -C, or -D in SW620 cells was determined
      by immunoblotting assays. Endostar inhibited tumor growth and the rate of lymph
      node metastasis (P < 0.01). The density of blood vessels in or around the tumor
      area was 12.27 +/- 1.21 and 22.25 +/- 2.69 per field in Endostar-treated mice and
      controls (P < 0.05), respectively. Endostar also decreased the density of
      lymphatic vessels in tumor tissues (7.84 +/- 0.81 vs. 13.83 +/- 1.08, P < 0.05).
      Endostar suppresses angiogenesis and lymphangiogenesis in the lymph nodes with
      metastases, simultaneously. The expression of VEGF-A, -C and -D in SW620 cells
      treated with Endostar was substantially lower than that of controls. Endostar
      inhibited growth and lymph node metastasis of colon cancer cells by inhibiting
      angiogenesis and lymphangiogenesis in a mouse xenograft model of colon cancer.

PMID- 21938483
TI  - Localization of caveolin-1 and c-src in mature and differentiating
      photoreceptors: raft proteins co-distribute with rhodopsin during development.
AB  - Numerous biochemical and morphological studies have provided insight into the
      distribution pattern of caveolin-1 and the presence of membrane rafts in the
      vertebrate retina. To date however, studies have not addressed the localization
      profile of raft specific proteins during development. Therefore the purpose of
      our studies was to follow the localization pattern of caveolin-1, phospho
      caveolin-1 and c-src in the developing retina and compare it to that observed in
      adults. Specific antibodies were used to visualize the distribution of caveolin
      1, c-src, a kinase phosphorylating caveolin-1, and phospho-caveolin-1. The
      labeling pattern of this scaffolded complex was compared to those of rhodopsin
      and rhodopsin kinase. Samples were analyzed at various time points during
      postnatal development and compared to adult retinas. The immunocytochemical
      studies were complemented with immunoblots and immunoprecipitation studies. In
      the mature retina caveolin-1 and c-src localized mainly to the cell body and IS
      of photoreceptors, with only very weakly labeled OS. In contrast, phospho
      caveolin-1 was only detectable in the OS of photoreceptors. During development we
      followed the expression and distribution profile of these proteins in a temporal
      sequence with special attention to the period when OS formation is most robust.
      Double labeling immunocytochemistry and immunoprecipitation showed rhodopsin to
      colocalize and co-immunoprecipitate with caveolin-1 and c-src. Individual
      punctate structures between the outer limiting membrane and the outer plexiform
      layer were seen at P10 to be labeled by both rhodopsin and caveolin-1 as well as
      by rhodopsin and c-src, respectively. These studies suggest that membrane raft
      specific proteins are co-distributed during development, thereby pointing to a
      role for such complexes in OS formation. In addition, the presence of small
      punctate structures containing caveolin-1, c-src and rhodopsin raise the
      possibility that these proteins may transport together to OS during development
      and that caveolin-1 exists predominantly in a phosphorylated form in the OS.

PMID- 21938484
TI  - Preliminary validation of a screening tool for adolescent panic disorder in
      pediatric primary care clinics.
AB  - This study examines the validity of a brief screening tool for adolescent panic
      disorder (PD) in a primary care setting. A total of 165 participants (ages 12-17
      years) seen in two pediatric primary care clinics completed the Autonomic Nervous
      System Questionnaire (ANS; Stein et al. in Psychosomatic Med 61:359-364, 40). A
      subset of those screening positive (n = 22) and negative (n = 23) for panic
      symptoms on the ANS completed follow-up phone interviews assessing fit with DSM
      IV criteria for panic disorder, self-reported anxiety and depression symptom
      severity, anxiety-related correlates, and functional impairment. A two-question
      version of the ANS demonstrated excellent sensitivity (Se = 1.00), but lower
      specificity (Sp = 0.47) for PD diagnostic status. Three-question and five
      question versions modestly improved specificity (Sp = 0.57 and 0.65,
      respectively). In addition, screen-positive participants reported higher panic
      symptoms, anxiety sensitivity, and functional impairment, relative to screen
      negative participants. Preliminary results suggest the ANS may be a valid
      screening tool for PD among adolescents, while simultaneously being brief and
      easy to score. Replication with larger samples is recommended as one related
      future research endeavor.

PMID- 21938485
TI  - Risk of ulcerative colitis-associated colorectal cancer in China: a multi-center
      retrospective study.
AB  - BACKGROUND: The number of patients with ulcerative colitis (UC) in China has
      increased in the past 10 years. Thus, it is anticipated that the incidence of UC
      associated colorectal cancer (UC-CRC) will also increase. However, the risk of
      CRC in UC patients is still unknown in Chinese. The aim of this study was to
      identify the risk and risk factors of UC-CRC in Chinese. METHODS: A total of
      3,922 patients with UC were retrospectively collected from five central teaching
      hospitals in China, in which high-quality endoscopic and histological diagnoses
      were available from 1998 to 2009. The database of the UC and UC-associated CRC
      patients was evaluated. RESULTS: CRC was diagnosed 34 in patients, and the
      overall prevalence of CRC in patients with UC was 0.87%. The cumulative risk of
      developing CRC after a disease duration of 10 years was 1.15% (95% confidence
      interval [CI] 0.71-1.84%); 20 years, 3.56% (95% CI 2.14-5.89%); and 30 years,
      14.36% (95% CI 7.57-26.3%). Longer disease duration, extensive colitis, and
      dysplasia found in the biopsy specimen were identified as risk factors for
      developing CRC. 5-ASA use was identified as a protective factor of UC-CRC.
      CONCLUSIONS: The period prevalence of CRC was lower than that reported from the
      West. However, the cumulative risk was found to be comparable to that of Western
      countries, which suggests that the period prevalence of UC-CRC in China may be
      growing in the future.

PMID- 21938486
TI  - Novel medical therapies of recurrent and metastatic gastroenteropancreatic
      neuroendocrine tumors.
AB  - Neuroendocrine tumors (NETs) of the gastrointestinal tract and pancreas are slow
      growing but commonly advanced malignancies with increasing incidence and
      prevalence. While locoregional disease can be effectively managed with resection,
      treatment of recurrent, progressive or metastatic disease has until recently been
      limited to palliative embolization and cytoreducitve surgery, with cytotoxic
      chemotherapeutic agents being the last resort. However, novel molecular targeted
      therapies inhibiting malignant cell proliferation and neoangiogenesis, as well as
      new cytotoxic chemotherapy drugs and somatostatin analogues, are all being
      investigated for their potential use in advanced neuroendocrine tumors. Long
      acting release forms of octreotide have been shown to not only improve symptoms
      in carcinoid syndrome but to also delay progression of gastrointestinal NETs. On
      the other hand, phase III trials have demonstrated everolimus (with octreotide)
      and sunitinib to increase progression-free survival in pancreatic NETs. Use of
      bevacizumab has also shown promise in a phase II study, and results of an ongoing
      phase III trial comparing it to interferon are eagerly expected. Use of
      radiolabeled somatostatin analogues is still under investigation, though several
      phase II studies are encouraging. New cytotoxic agents, most notably temozolomide
      and capecitabine, are already in use, but their relative effectiveness compared
      to streptozocin in pancreatic NETs is yet to be determined.

PMID- 21938487
TI  - Death receptor 5 and neuroproliferation.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand or Apo2 ligand is a
      member of the tumor necrosis factor superfamily of cytokines that induces
      apoptosis upon binding to its death domain-containing transmembrane receptors,
      death receptors 4 and 5 (DR4, DR5). However, DR5 is also expressed in the
      developing CNS where it appears to play a role unrelated to apoptosis, and
      instead may be involved in the regulation of neurogenesis. We report on the
      distribution of DR5 expression in mouse hippocampus, cerebellum, and rostral
      migratory stream (RMS) of olfactory bulb from embryonic (E) day 16 (E16) to
      postnatal (P) day (P180). At E16, DR5-positive cells were distributed widely in
      embryonic hippocampus with strong immunostaining in the developing dentate gyrus.
      In newborn hippocampus, DR5-positive cells were predominantly located in
      proliferative zones, such as dentate gyrus, subventricular zone, and RMS. After
      postnatal day 7 (P7), the number of DR5-positive cells decreased, and cells with
      intense fluorescence were primarily restricted to the subgranular layer (SGL),
      although the granular cell layer showed weak fluorescence. After P30, only few
      DR5-positive cells were found in SGL, and mature granule cells were negative for
      DR5 expression. To address whether DR5 expression is a restricted to progenitor
      cells and newborn neurons, we performed 5-bromo-deoxyuridine labeling. We report
      that proliferative cells in the SGL selectively express DR5, with lower levels of
      expression in cells positive for doublecortin, a marker of newborn neurons. In
      addition, the stem cells in intestine, cerebellum, and RMS were also demonstrated
      to be DR5-positive. In the meantime, in cerebellum, DR5-positive cells were also
      positive for glial fibrillary acidic protein, a marker of proliferative Bergmann
      cells. We conclude that DR5 is selectively expressed by neuroprogenitor cells and
      newborn neurons, suggesting that the DR5 death receptor is likely to play a key
      role in neuroproliferation and differentiation.

PMID- 21938488
TI  - Angiotensin II AT(1) receptor blockers ameliorate inflammatory stress: a
      beneficial effect for the treatment of brain disorders.
AB  - Excessive allostatic load as a consequence of deregulated brain inflammation
      participates in the development and progression of multiple brain diseases,
      including but not limited to mood and neurodegenerative disorders. Inhibition of
      the peripheral and brain Renin-Angiotensin System by systemic administration of
      Angiotensin II AT(1) receptor blockers (ARBs) ameliorates inflammatory stress
      associated with hypertension, cold-restraint, and bacterial endotoxin
      administration. The mechanisms involved include: (a) decreased inflammatory
      factor production in peripheral organs and their release to the circulation; (b)
      reduced progression of peripherally induced inflammatory cascades in the cerebral
      vasculature and brain parenchyma; and (c) direct anti-inflammatory effects in
      cerebrovascular endothelial cells, microglia, and neurons. In addition, ARBs
      reduce bacterial endotoxin-induced anxiety and depression. Further pre-clinical
      experiments reveal that ARBs reduce brain inflammation, protect cognition in
      rodent models of Alzheimer's disease, and diminish brain inflammation associated
      with genetic hypertension, ischemia, and stroke. The anti-inflammatory effects of
      ARBs have also been reported in circulating human monocytes. Clinical studies
      demonstrate that ARBs improve mood, significantly reduce cognitive decline after
      stroke, and ameliorate the progression of Alzheimer's disease. ARBs are well
      tolerated and extensively used to treat cardiovascular and metabolic disorders
      such as hypertension and diabetes, where inflammation is an integral pathogenic
      mechanism. We propose that including ARBs in a novel integrated approach for the
      treatment of brain disorders such as depression and Alzheimer's disease may be of
      immediate translational relevance.

PMID- 21938489
TI  - Taxol-induced alteration of intracellular amino-acid profile related to human
      cervical carcinoma HeLa cell death.
AB  - The anti-tumor action of Taxol was investigated in the changes of amino-acids
      involved in tumor cell survival. By tracing the intracellular amino-acid profiles
      of HeLa cells treated with non-conditioned and three conditioned media (Taxol, L
      alanine, and Taxol + L-alanine), it was observed that an alteration of amino-acid
      metabolism participates in Taxol-induced death of HeLa cells. The contents of 18
      out of 21 detected amino-acids are 5-95% and the ones of lysine and methionine
      are 158 and 117% of the corresponding contents in the control after treatment
      with Taxol for 24 h, respectively. Addition of L-alanine inhibited cell apoptosis
      upon Taxol treatment by partially blocking the increase of lysine and methionine
      and reversing decrease trend of alanine, glycine, and glutamic acid. These
      results suggest that interference of amino-acid metabolism might be an important
      mechanism of Taxol cytotoxicity.

PMID- 21938490
TI  - Immunopathology of mastitis: insights into disease recognition and resolution.
AB  - Mastitis is an inflammation of the mammary gland commonly caused by bacterial
      infection. The inflammatory process is a normal and necessary immunological
      response to invading pathogens. The purpose of host inflammatory responses is to
      eliminate the source of tissue injury, restore immune homeostasis, and return
      tissues to normal function. The inflammatory cascade results not only in the
      escalation of local antimicrobial factors, but also in the increased movement of
      leukocytes and plasma components from the blood that may cause damage to host
      tissues. A precarious balance between pro-inflammatory and pro-resolving
      mechanisms is needed to ensure optimal bacterial clearance and the prompt return
      to immune homeostasis. Therefore, inflammatory responses must be tightly
      regulated to avoid bystander damage to the milk synthesizing tissues of the
      mammary gland. The defense mechanisms of the mammary gland function optimally
      when invading bacteria are recognized promptly, the initial inflammatory response
      is adequate to rapidly eliminate the infection, and the mammary gland is returned
      to normal function quickly without any noticeable clinical symptoms. Suboptimal
      or dysfunctional mammary gland defenses, however, may contribute to the
      development of severe acute inflammation or chronic mastitis that adversely
      affects the quantity and quality of milk. This review will summarize critical
      mammary gland defense mechanisms that are necessary for immune surveillance and
      the rapid elimination of mastitis-causing organisms. Situations in which
      diminished efficiency of innate or adaptive mammary gland immune responses may
      contribute to disease pathogenesis will also be discussed. A better understanding
      of the complex interactions between mammary gland defenses and mastitis-causing
      pathogens should prove useful for the future control of intramammary infections.

PMID- 21938491
TI  - [Classification and treatment of patella fractures].
AB  - Patella fractures are rare and account for approximately 1% of all fractures.
      They are classified regarding their localization (proximal, distal) and
      appearance. The aim of any treatment is reconstruction of the extensor mechanism
      and joint surface. If dislocation and cartilage steps are less than 2 mm,
      conservative treatment may be indicated. Operative treatment is only necessary if
      a dislocation is more than 2 mm or when the extensor mechanism is unstable.
      Depending on the shape of the fracture, tension band wiring, interfragmentary
      screw fixation and combinations are the main techniques. Because patellectomy has
      functionally the worst result it should be avoided. Sleeve fractures (children)
      need exact reconstruction of the joint surface. In elderly patients conservative
      treatment or surgical patella-enclosing wiring techniques for stabilization are
      the best options due to low bone quality.

PMID- 21938492
TI  - [Anatomy and biomechanics of the patellofemoral joint: physiological conditions
      and changes after total knee arthroplasty].
AB  - The patellofemoral joint constitutes a complex anatomical and functional entity.
      The tensile force of the quadriceps femoris muscle is transmitted through the
      patella and patellar ligament onto the tibial tuberosity. This particular three
      dimensional arrangement increases the torsional moment acting on the knee joint.
      Dynamic alignment of the patella is determined by trochlear geometry and is
      supported by active muscular and passive connective tissue stabilizers. In
      addition to the retinaculum of the patella, the medial patellofemoral ligament is
      attracting increasing clinical attention. Multidirectional motion of the patella
      is closely connected to retropatellar pressure distribution which can be
      modulated by moving the patellar ligament insertion. Implantation of a knee
      endoprosthesis changes the joint surface geometry and consequently patella
      kinematics and retropatellar pressure distribution. Finite element analysis
      provides the possibility to assess retropatellar pressure distribution before and
      after implantation of prostheses.

PMID- 21938493
TI  - The history and future of probenecid.
AB  - Probenecid was initially developed with the goal of reducing the renal excretion
      of antibiotics, specifically penicillin. It is still used for its uricosuric
      properties in the treatment in gout, but its clinical relevance has sharply
      fallen and is rarely used today for either. Interestingly, throughout the last 60
      years, there have been a host of apparently unrelated studies using probenecid in
      the clinical and basic research arena, including its potential use in the
      diagnosis and treatment of depression and its use to prevent fura-2 leakage in
      calcium transient studies. Recently, it has been shown that it is also an agonist
      of the Transient Receptor Potential Vanilloid 2 channel. Due to its unique action
      and new findings implicating TRPV channels in physiology and in disease,
      probenecid may have a new future as a research tool, and perhaps as a clinical
      agent in the neurology and cardiology fields. We review the history of probenecid
      in this paper and its potential future uses.

PMID- 21938494
TI  - S100-A10, thioredoxin, and S100-A6 as biomarkers of papillary thyroid carcinoma
      with lymph node metastasis identified by MALDI imaging.
AB  - In papillary thyroid carcinoma (PTC), metastasis is a feature of an aggressive
      tumor phenotype. To identify protein biomarkers that distinguish patients with an
      aggressive tumor behavior, proteomic signatures in metastatic and non-metastatic
      tumors were investigated comparatively. In particular, matrix-assisted laser
      desorption/ionization (MALDI) imaging mass spectrometry (IMS) was used to analyze
      primary tumor samples. We investigated a tumor cohort of PTC (n = 118) that were
      matched for age, tumor stage, and gender. Proteomic screening by MALDI-IMS was
      performed for a discovery set (n = 29). Proteins related to the discriminating
      mass peaks were identified by 1D-gel electrophoresis followed by mass
      spectrometry. The candidate proteins were subsequently validated by
      immunohistochemistry (IHC) using a tissue microarray for an independent PTC
      validation set (n = 89). In this study, we found 36 mass-to-charge-ratio (m/z)
      species that specifically distinguished metastatic from non-metastatic tumors,
      among which m/z 11,608 was identified as thioredoxin, m/z 11,184 as S100-A10, and
      m/z 10,094 as S100-A6. Furthermore, using IHC on the validation set, we showed
      that the overexpression of these three proteins was highly associated with lymph
      node metastasis in PTC (p < 0.005). For functional analysis of the metastasis
      specific proteins, we performed an Ingenuity Pathway Analysis and discovered a
      strong relationship of all candidates with the TGF-beta-dependent EMT pathway.
      Our results demonstrated the potential application of the MALDI-IMS proteomic
      approach in identifying protein markers of metastasis in PTC. The novel protein
      markers identified in this study may be used for risk stratification regarding
      metastatic potential in PTC.

PMID- 21938495
TI  - Comparison of treatment results between surgery alone, preoperative short-course
      radiotherapy, or long-course concurrent chemoradiotherapy in locally advanced
      rectal cancer.
AB  - BACKGROUND: The aim of this study is to compare the results between surgery
      alone, preoperative radiotherapy (RT), or preoperative concurrent
      chemoradiotherapy (CCRT) followed by surgery in the treatment of locally advanced
      rectal cancer in Asian patients. METHODS: This study included 151 consecutive
      patients with clinical T3, T4 or node-positive rectal cancer from Jan. 2005 to
      Dec. 2007. Eighty-six patients underwent total mesorectal excision (TME) alone,
      28 patients received preoperative RT (25 Gy in 5 fractions) followed by TME in 1
      week, and 37 patients received preoperative CCRT (50.4 Gy in 28 fractions)
      followed by TME in 4-6 weeks. RESULTS: The 3-year loco-regional recurrence (LRR),
      distant metastasis, overall and disease-free survival rates are comparable among
      Surgery, RT and CCRT groups. By multivariate analysis, pT4, distal margin <2 cm,
      the ratio of positive lymph nodes to totally dissected lymph nodes >= 0.2, and
      non-R0 resection were significant factors for LRR. In subgroup analysis, TME
      alone produced comparable LRR to RT or CCRT (3.3 vs.. 4.8%) for favorable
      patients (0-1 risk factors). For unfavorable patients (2 or more risk factors),
      the LRR rose to 37% in patients receiving surgery alone as compared with 15% in
      the RT or CCRT patients. CONCLUSIONS: Preoperative RT or CCRT followed by TME
      produced good local control in favorable and unfavorable patients with locally
      advanced rectal cancer. If preoperative RT or CCRT is not given, TME alone has a
      high incidence of local recurrence in unfavorable patients with 2 or more risk
      factors.

PMID- 21938496
TI  - A West Nile virus vaccine.

PMID- 21938497
TI  - Effect of iodine source and dose on growth and iodine content in tissue and
      plasma thyroid hormones in fattening pigs.
AB  - PURPOSE: The aim of the present feeding trial with iodine was to assess pigs'
      growth performance and carcass characteristics, the iodine accumulation in
      tissues, and their influences on the thyroid hormones in plasma. METHODS: Eighty
      pigs (33-115 kg body weight) were allotted to 5 dietary treatments: a control
      group (150 MUg I/kg), two potassium iodide [KI] groups (4,000 and 10,000 MUg
      I/kg), and two potassium iodate [KIO3] groups (4,000 and 10,000 MUg I/kg). Iodine
      concentration was determined in thyroid gland, liver, kidney, muscle, fat, and
      skin by ICP-MS. Furthermore, thyroxine (T4) and triiodothyronine (T3) in plasma
      were evaluated. RESULTS: High dietary iodine tended to have a negative effect on
      younger animals' growth (average daily gain, ADG). However, during the entire
      growth period, the growth performance and carcass characteristics were not
      influenced by iodine dosages or sources. Irrespective of iodine source, higher
      iodine doses of diets affected higher iodine stores in all tested tissues except
      for abdominal fat. Thus, iodine supplementation with 10,000 MUg I/kg feed
      significantly increased iodine content in thyroid gland (+122%), liver (+260%),
      kidney (+522%), muscle (+131%), and skin (+321%) compared to the control group.
      However, there was no significance of thyroid hormones in plasma. CONCLUSIONS: As
      a result, pork and fat of pigs showed only low iodine accumulation even in the
      high-iodine groups. Thus, there should be no risk of an iodine excess in human
      nutrition and animal health, and the EU-upper level for iodine in pig feed can be
      maintained.

PMID- 21938498
TI  - [Documentation of the diagnostic quality of hospitals: evaluation of autopsy
      reports].
AB  - Multiple factors have affected the decline in autopsy rates. Discrepancies
      between clinical diagnoses and findings at autopsy are frequently used as an
      argument for a high autopsy rate. However, the quality of the diagnosis is
      independent of the autopsy rate. A long-term study covering the years 1972-2002
      in the University Hospital Zurich has documented a significant reduction of
      diagnostic errors in internal medicine. Major diagnostic errors (class 1)
      declined from 16% (1972), to 9% (1982), to 7% (1992) to 2% (2002). The main
      reason is the availability of new diagnostic procedures. In 2010 the analysis of
      class 1 diagnostic errors throughout the hospital documented class 1
      discrepancies in only 1%. This low number of diagnostic errors has been published
      in the annual quality report of the University Hospital Zurich. The documentation
      of this improvement in the quality report of the hospital provides the
      opportunity to convince clinicians, health politicians and the hospital
      administration to support autopsies in teaching as well as non-teaching
      hospitals.

PMID- 21938499
TI  - Reconstructing the fungal tree of life using phylogenomics and a preliminary
      investigation of the distribution of yeast prion-like proteins in the fungal
      kingdom.
AB  - We have used three independent phylogenomic approaches (concatenated alignments,
      single-, and multi-gene supertrees) to reconstruct the fungal tree of life (FTOL)
      using publicly available fungal genomes. This is the first time multi-gene
      families have been used in fungal supertree reconstruction and permits us to use
      up to 66% of the 1,001,217 genes in our fungal database. Our analyses show that
      different phylogenomic datasets derived from varying clustering criteria and
      alignment orientation do not have a major effect on phylogenomic supertree
      reconstruction. Overall the resultant phylogenomic trees are relatively congruent
      with one another and successfully recover the major fungal phyla, subphyla and
      classes. We find that where incongruences do occur, the inferences are usually
      poorly supported. Within the Ascomycota phylum, our phylogenies reconstruct
      monophyletic Saccharomycotina and Pezizomycotina subphyla clades and infer a
      sister group relationship between these to the exclusion of the Taphrinomycotina.
      Within the Pezizomycotina subphylum, all three phylogenies infer a sister group
      relationship between the Leotiomycetes and Sordariomycetes classes. However,
      there is conflict regarding the relationships with the Dothideomycetes and
      Eurotiomycetes classes. Within the Basidiomycota phylum, supertrees derived from
      single- and multi-gene families infer a sister group relationship between the
      Pucciniomycotina and Agaricomycotina subphyla while the concatenated phylogeny
      infers a poorly supported relationship between the Agaricomycotina and
      Ustilagomycotina. The reconstruction of a robust FTOL is important for future
      fungal comparative analyses. We illustrate this point by performing a preliminary
      investigation into the phyletic distribution of yeast prion-like proteins in the
      fungal kingdom.

PMID- 21938500
TI  - The effects of peak and mid-luteal estradiol levels on in vitro fertilization
      outcome.
AB  - PURPOSES: To evaluate the role of peak E2 level and its ratio to mid-luteal E2
      level on implantation and clinical pregnancy rates in patients undergoing IVF
      cycles. METHODS: A retrospective study was designed covering 106 patients who
      were admitted to IVF Unit between June and October 2008. The patients were
      divided into two groups with respect to peak E2 levels. Ovulation induction has
      been done via standard long agonist protocol. Blood samples were drawn on the day
      of (hCG) administration and 8 days after embryo transfer for serum E2,
      progesterone measurements. RESULTS: The mean peak E2 level was 2,697.4 +/- 1,453
      pg/ml (range 684-4,983 pg/ml. The number of retrieved oocytes, luteal E2 level,
      peak E2 level and E2 ratio were significantly higher in E2 >2,500 group, however,
      the implantation rate was significantly lower in this group. There were
      statistically significant differences in peak E2 levels, luteal E2 levels,
      retrieved oocytes, E2 ratios; of the women who got pregnant and did not get
      pregnant, all the above parameters were significantly higher in non-pregnant
      group. According to E2 ratios, the clinical pregnancy rate was highest in group 1
      and significantly lowest in group 3. CONCLUSION: This study has shown that the
      high E2 level and mid-luteal decline of E2 which were defined as peak E2
      level/mid-luteal E2 level were predictive for implantation rate in IVF cycles.

PMID- 21938501
TI  - Chlamydial infection in a high risk population: association with vaginal flora
      patterns.
AB  - PURPOSE: This study aimed to determine the frequency of Chlamydia trachomatis
      (CT) infection among high risk Brazilian women and evaluate its association with
      vaginal flora patterns. METHODS: This was a cross-sectional study, performed in
      an outpatient clinic of Bauru State Hospital, Sao Paulo, Brazil. A total of 142
      women were included from 2006 to 2008. Inclusion criteria was dyspareunia, pain
      during bimanual exam, presence of excessive cervical mucus, cervical ectopy or
      with three or more episodes of abnormal vaginal flora (AVF) in the previous year
      before enrollment. Endocervical CT testing was performed by PCR. Vaginal swabs
      were collected for microscopic assessment of the microbial flora pattern. Gram
      stained smears were classified in normal, intermediate or bacterial vaginosis
      (BV), and recognition of Candida sp. morphotypes. Wet mount smears were used for
      detection of Trichomonas vaginalis and aerobic vaginitis (AV). RESULTS: Thirty
      four of 142 women (23.9%) tested positive for CT. AVF was found in 50 (35.2%)
      cases. The most frequent type of AVF was BV (17.6%). CT was strongly associated
      with the presence of AV (n = 7, 4.9%, P = 0.018), but not BV (n = 25, 17.6%, P =
      0.80) or intermediate flora (n = 18, 12.7%, P = 0.28). CONCLUSIONS: A high rate
      of chlamydial infection was found in this population. Chlamydia infection is
      associated with aerobic vaginitis.

PMID- 21938503
TI  - Journals publishing bio-medicolegal research in Europe.
AB  - Fragmentation of bio-medicolegal knowledge has led to a proliferation of ultra
      specialised sub-disciplines and branches, often published in 'field-oriented'
      scientific journals.The aim of this work is to provide an in-depth analytical
      picture of bio-medicolegal sources of publication, within and outside the
      traditional conception of legal medicine. An extensive search of bio-medicolegal
      articles published in the last five and a half years was performed on the MEDLINE
      database according to MeSH terms combined with free-text protocols. We performed
      a systematic analysis of targeted journals after merging, selecting and
      categorising all retrieved records, taking into account data from the 2009 JCR
      Science Edition (released on June 2010); 1,037 different journals were
      identified, of which only 48 (4.6%) focus specifically on bio-medicolegal
      matters, and of which only seven (14.6%) have an impact factor (IF). Despite this
      apparent dispersion, 47% of articles were published in bio-medicolegal journals
      (BML), of which 70.2% were in journals with IF (BML-IF). Articles published in
      BML-IF journals (33% of total papers) reach almost 50%, mainly in "Forensic
      Science International", "International Journal of Legal Medicine" and "Journal of
      Forensic Sciences". Instead, publications in not specifically bio-medicolegal
      journals (Not BML-IF) are greatly scattered and even fragmented in about 650
      journals.The sub-disciplines that appear most frequently in Not BML-IF rather
      than BML-IF journals are Forensic Psychiatry (48.2% vs. 5.1%), Criminology (37.1%
      vs. 8.3%), Malpractice (50.7% vs. 4.0%), Medical Law and Ethics (46.4% vs. 6.9%)
      and Clinical Forensic Medicine (39.5% vs. 21.3%). The proposed bibliometric
      analysis revealed the preference of Forensic Pathology, Criminalistics
      (Biological), Forensic Genetics, Forensic Anthropology and Forensic Entomology
      for journals traditionally considered pertinent to the medico-legal discipline,
      with a considerable dispersion involving Toxicology, Psychiatry, Criminology and
      Malpractice, which were published in less well-known journals. This dispersion
      could be reduced adapting specialised forensic sections and increasing the IF of
      forensic journals, in order to respond suitably to the present demand for
      visibility by bio-medicolegal scientists, clearly oriented towards enhancing the
      objective impact of their curricula and attempting to attract funding to their
      research projects.

PMID- 21938504
TI  - "Free" copper: a new endogenous chemical mediator of inflammation in birds.
AB  - For acceptance of any chemical agent as an endogenous chemical mediator of
      inflammation, the agent in question must fulfill some biological requirements
      which are (a) it should be ubiquitously present in tissues in inactive form, (b)
      it should be activated during process of inflammation whose increase should be
      identifiable, (c) it should induce or amplify some events of inflammation, (d)
      there must be some natural inhibitor of such active form in tissues, (e) it
      should be able to induce inflammatory reaction after exogenous injection, (f)
      such reaction should be inhibited by exogenous use of their antagonists, and (g)
      it should be amplified by use of agonists. Copper in its protein free or protein
      bound form are reported to act as pathogenic factor in inflammatory processes due
      to oxidative stress. But their role as endogenous chemical mediator of
      inflammation does not appear to be investigated thoroughly in light of
      abovementioned biological criterion of mediator. Present study aims at thorough
      exploration on role of free copper as endogenous chemical mediator of
      inflammation in light of above facts. It was done by estimation of total copper,
      protein-bound copper, and free copper along with estimation of free radical
      generation, increase in vascular permeability, and cellular infiltration during
      acute inflammatory reaction induced by carrageenan and concanavalin using chicken
      skin as test model. It was further evaluated by use of exogenous free copper in
      experimental model and their subsequent inhibition and amplification by chemical
      chelators of copper. Present study confirms that free copper fulfilled all the
      biological requirements for accepting it as an endogenous chemical mediator of
      inflammation.

PMID- 21938505
TI  - Contrast-enhanced US (CEUS) in children: ready for prime time in the United
      States.

PMID- 21938506
TI  - Correlation between US and MRI for prenatal lung volumetry in diaphragmatic
      hernia, and use of Doppler to identify the ipsilateral lung cap.
AB  - BACKGROUND: Pulmonary hypoplasia is a common cause of neonatal death. OBJECTIVE:
      To describe the correlation between relative fetal lung volume (RFLV) and lung-to
      head ratio (LHR) in fetuses with unilateral diaphragmatic hernia. Additionally,
      to describe identification of the ipsilateral lung cap by power Doppler.
      MATERIALS AND METHODS: Single-institution study of consecutive fetuses with
      diaphragmatic hernia. LHR (by US) and RFLV (by MRI) were correlated in fetuses
      with and without an ipsilateral lung cap seen at MRI. In four, color/power
      Doppler was used to follow the pulmonary artery of the ipsilateral lung to
      identify the compressed cap. RESULTS: The study included 48 fetuses of 20-38
      weeks' gestational age (mean, 26 weeks). Mean LHR was 1.52 (range, 0.6-3) in
      fetuses with a lung cap and 1.15 (range, 0.6-2.58) in fetuses without (P =
      0.043). Mean RFLV was 47.4% (range, 18-80%) in fetuses with and 32.9% (range, 14
      57%) in fetuses without a lung cap (P = 0.005). RFLV and LHR correlated (r =
      0.41, P = 0.01 in those with a cap; r = 0.50, P = 0.05 in those without). Power
      Doppler identified the ipsilateral lung cap and pulsed Doppler confirmed
      pulmonary vascularization in four of four fetuses. CONCLUSION: LHR underestimates
      lung volume in fetuses with an ipsilateral lung cap. Power Doppler may be useful
      for identifying the cap.

PMID- 21938507
TI  - Intermediate filament genes as differentiation markers in the leech Helobdella.
AB  - The intermediate filament (IF) cytoskeleton is a general feature of
      differentiated cells. Its molecular components, IF proteins, constitute a large
      family including the evolutionarily conserved nuclear lamins and the more diverse
      collection of cytoplasmic intermediate filament (CIF) proteins. In vertebrates,
      genes encoding CIFs exhibit cell/tissue type-specific expression profiles and are
      thus useful as differentiation markers. The expression of invertebrate CIFs,
      however, is not well documented. Here, we report a whole-genome survey of IF
      genes and their developmental expression patterns in the leech Helobdella, a
      lophotrochozoan model for developmental biology research. We found that, as in
      vertebrates, each of the leech CIF genes is expressed in a specific set of
      cell/tissue types. This allows us to detect earliest points of differentiation
      for multiple cell types in leech development and to use CIFs as molecular markers
      for studying cell fate specification in leech embryos. In addition, to determine
      the feasibility of using CIFs as universal metazoan differentiation markers, we
      examined phylogenetic relationships of IF genes from various species. Our results
      suggest that CIFs, and thus their cell/tissue-specific expression patterns, have
      expanded several times independently during metazoan evolution. Moreover,
      comparing the expression patterns of CIF orthologs between two leech species
      suggests that rapid evolutionary changes in the cell or tissue specificity of
      CIFs have occurred among leeches. Hence, CIFs are not suitable for identifying
      cell or tissue homology except among very closely related species, but they are
      nevertheless useful species-specific differentiation markers.

PMID- 21938508
TI  - The diversity of polyketide synthase genes from sugarcane-derived fungi.
AB  - The chemical ecology and biotechnological potential of metabolites from
      endophytic and rhizosphere fungi are receiving much attention. A collection of 17
      sugarcane-derived fungi were identified and assessed by PCR for the presence of
      polyketide synthase (PKS) genes. The fungi were all various genera of
      ascomycetes, the genomes of which encoded 36 putative PKS sequences, 26 shared
      sequence homology with beta-ketoacyl synthase domains, while 10 sequences showed
      homology to known fungal C-methyltransferase domains. A neighbour-joining
      phylogenetic analysis of the translated sequences could group the domains into
      previously established chemistry-based clades that represented non-reducing,
      partially reducing and highly reducing fungal PKSs. We observed that, in many
      cases, the membership of each clade also reflected the taxonomy of the fungal
      isolates. The functional assignment of the domains was further confirmed by in
      silico secondary and tertiary protein structure predictions. This genome mining
      study reveals, for the first time, the genetic potential of specific taxonomic
      groups of sugarcane-derived fungi to produce specific types of polyketides.
      Future work will focus on isolating these compounds with a view to understanding
      their chemical ecology and likely biotechnological potential.

PMID- 21938509
TI  - Major depressive disorder during pregnancy and emotional attachment to the fetus.
AB  - While there is good evidence that depression negatively impacts mother-to-infant
      emotional attachment in the postpartum period, the impact of depression in
      pregnancy on maternal emotions and cognitions about the fetus (often termed
      "maternal-fetal attachment" or MFA) is unclear. This study compared MFA scores
      from women meeting clinical criteria for Major Depressive Disorder (MDD) with
      scores from nondepressed women. Participants were 161 women enrolled at 23-36
      weeks gestation, of whom 65 met criteria for MDD via the Structured Clinical
      Interview for the DSM-IV-TR during their second and/or third trimesters.
      Cranley's Maternal Fetal Attachment Scale was administered at 26 and 36 weeks
      gestation. Generalized linear modeling was used to assess the effect of MDD,
      anxiety, and antidepressant use on MFA. MDD was negatively related to MFA (LR) =
      4.58, df = 1, p < 0.04). Neither anxiety (LR = 0.22, p < 0.64), nor
      antidepressant use (LR = 0.20, df = 1, p < 0.66) were related to MFA. Depression
      severity was negatively related to MFAS scores (B = -0.005, SE = .002, p <
      0.0012) when including the interaction of MDD group and HRSD scores in the model.
      This study is the first to demonstrate that clinically defined MDD during
      pregnancy negatively impacts MFA, suggesting that the basis for poor mother-to
      infant attachment in postpartum MDD may have roots in pregnancy.

PMID- 21938510
TI  - Developmental, malignancy-related, and cross-species analysis of eosinophil, mast
      cell, and basophil siglec-8 expression.
AB  - OBJECTIVE: The aim of this study is to determine when during hematopoiesis Siglec
      8 gets expressed, whether it is expressed on hematologic malignancies, and if
      there are other non-human species that express Siglec-8. METHODS: Siglec-8 mRNA
      and cell surface expression was monitored during in vitro maturation of human
      eosinophils and mast cells. Flow cytometry was performed on human blood and bone
      marrow samples, and on blood samples from dogs, baboons, and rhesus and
      cynomolgus monkeys. RESULTS: Siglec-8 is a late maturation marker. It is
      detectable on eosinophils and basophils from subjects with chronic eosinophilic
      leukemia, chronic myelogenous leukemia, and on malignant and non-malignant bone
      marrow mast cells, as well as the HMC-1.2 cell line. None of the Siglec-8
      monoclonal antibodies tested recognized leukocytes from dogs, baboons, and rhesus
      and cynomolgus monkeys. CONCLUSIONS: Siglec-8-based therapies should not target
      immature human leukocytes but should recognize mature and malignant eosinophils,
      mast cells, and basophils. So far, there is no suitable species for preclinical
      testing of Siglec-8 monoclonal antibodies.

PMID- 21938512
TI  - Alkaptonuria: treasure your exceptions.

PMID- 21938511
TI  - Transgenic mice that overexpress human IL-15 in enterocytes recapitulate both B
      and T cell-mediated pathologic manifestations of celiac disease.
AB  - Celiac disease (CD) is a chronic immune-mediated intestinal inflammatory disorder
      afflicting genetically susceptible individuals triggered by the consumption of
      dietary cereals with high gluten content. As with many other organ-specific
      autoimmune diseases, the dominant tissue-destructive inflammation in CD is T cell
      mediated. The proinflammatory cytokine IL-15 that is overexpressed in the
      intestinal epithelium of CD patients has emerged as a pivotal element that
      orchestrates intestinal inflammation and T cell-mediated autoimmune tissue
      destruction. Although no animal model exists that recapitulates the full spectrum
      of CD pathophysiology, we have previously reported that transgenic mice that
      overexpress human IL-15 in enterocytes (T3(b)-hlL-15 Tg) display many of the T
      cell-mediated pathologic features seen in CD. Extending these observations, we
      now report that T3(b)-hlL-15 Tg mice in addition to recapitulating T cell
      mediated effects also display autoantibodies including those against tissue
      transglutaminase 2 and extensive lamina propria plasmacytosis, all of which are
      characteristic of CD, thereby reflecting the possibility that locally expressed
      IL-15 drives both T and B cell pathologic effects seen in CD. More importantly,
      these findings support the validity and utility of T3(b)-hlL-15 Tg mice as a
      reasonable model to investigate not only tissue-destructive pathologic processes
      in CD, but also to explore novel therapeutic modalities for the treatment of this
      disease.

PMID- 21938513
TI  - Accountability, governance and biobanks: the ethics and governance committee as
      guardian or as toothless tiger?
AB  - The huge potential of biobanks/genetic databases for the research community has
      been recognised across jurisdictions in both publicly funded and commercial
      sectors. But although there is tremendous potential there are likewise potential
      difficulties. The long-term storage of personal health information and samples
      poses major challenges. This is an area is fraught with ethical and legal
      uncertainties. Biobanks raise many questions of the control of rights, of
      consent, of privacy and confidentiality and of property in human material. It is
      thus unsurprising then that there has been a lively debate as to how biobanks
      should operate, the boundaries of participation and what governance structure, if
      any they should adopt, a debate which has been engaged in across the academic
      community and by funders and researchers alike. This paper asks despite the good
      intentions can ad hoc ethics and ethics and governance committees long term
      provide an effective solution to the legal and regulatory challenges arising from
      biobanks.

PMID- 21938514
TI  - Monitoring of hexabromocyclododecane diastereomers in fish from European
      freshwaters and estuaries.
AB  - BACKGROUND AND AIMS: Hexabromocyclododecane (HBCD) is a brominated flame
      retardant used mainly in polystyrene foam as well as in textile applications. In
      recent years, measures were taken to reduce HBCD emissions during its production
      and use. To evaluate the efficacy of these measures, a monitoring project was
      initiated with fish as bioaccumulation indicators. METHODS: Since 2007 bream was
      sampled annually at several European freshwater sites applying standardized
      methods. Muscle samples were analyzed by a validated liquid chromatography-tandem
      mass spectrometry (LC-MS/MS) method which allows the quantification of alpha-,
      beta-, and gamma-diastereomers of HBCD. DISCUSSION: In most samples, alpha-HBCD
      was predominant. The lowest HBCD levels (11 MUg/kg lipid weight (lw), sum of
      three HBCD diastereomers) were detected in bream sampled in 2009 from Lake Belau
      which is situated in a rural area of Northern Germany. During the 4-year study
      period, statistical significant decreases of HBCD concentrations were detected in
      bream from the rivers Rhone (France; -85%, level 2010, 205 MUg/kg lw) and Western
      Scheldt (the Netherlands; -60%, level 2010, 36 MUg/kg lw). High HBCD
      concentrations (9,480-14,500 MUg/kg lw) without a clear time trend were observed
      in bream from the river Tees (UK). These high levels are in line with published
      data for fish from contaminated regions. CONCLUSIONS: Overall, the results
      indicate that environmental burdens of HBCD are decreasing at those locations
      where point sources and more diffuse emissions are expected.

PMID- 21938515
TI  - The Arabidopsis AtbZIP1 transcription factor is a positive regulator of plant
      tolerance to salt, osmotic and drought stresses.
AB  - According to the AtGenExpress transcriptome data sets, AtbZIP1 is an Arabidopsis
      gene induced by several abiotic stresses, such as salt, cold and drought. Here,
      we isolated AtbZIP1, and used semi-quantitative reverse transcription-PCR to
      verify that AtbZIP1 expression was indeed significantly induced by salt, osmotic,
      and cold stresses in Arabidopsis. AtbZIP1 knockout mutants showed a reduced
      tolerance to salt and osmotic stresses, coinciding with a suppression of the
      expression of several stress-responsive genes, such as COR15A, RD17 and RD29A.
      Consistently, the restoration of AtbZIP1 in the knockout lines restored the
      plants ability to tolerate salt and osmotic stresses. Furthermore, overexpressing
      AtbZIP1 in the wild type Arabidopsis resulted in an enhanced tolerance to salt
      and drought stresses. Sequence analysis shows that AtbZIP1 belongs to the S
      subfamily of basic leucine zipper transcription factors (TFs). The transient
      expression of green fluorescent protein-AtbZIP1 in tobacco leaf cells showed that
      AtbZIP1 localizes in nuclei. A transactivation assay further suggested that
      AtbZIP1 functions as a transcriptional activator in yeast and the two protein
      motifs (aa 13-38 and 92-118) are indispensable for transactivation activity.
      These results indicate that the TF AtbZIP1 is a positive regulator of plant
      tolerance to salt, osmotic, and drought stresses.

PMID- 21938516
TI  - Molecular identification and functional characterization of cytochrome P450
      monooxygenases from the brown-rot basidiomycete Postia placenta.
AB  - We explored the molecular diversity and functional capabilities of cytochrome
      P450 monooxygenases (P450s) from the brown-rot basidiomycete Postia placenta.
      Using bioinformatic and experimental data, we found 250 genes of P450s in the
      whole genome, including 60 putative allelic variants. Phylogenetic analysis
      revealed the presence of 42 families, including 18 novel families. Comparative
      phylogenetic analysis of P450s from P. placenta and the white-rot basidiomycete
      Phanerochaete chrysosporium suggested that vigorous gene duplication and
      molecular evolution occurred after speciation of basidiomycetes. Among the 250
      gene models, 184 were isolated as full-length cDNA and transformed into
      Saccharomyces cerevisiae to construct a functional library in which recombinant
      P450s were co-expressed with yeast NADPH-P450 oxidoreductase. Using this library,
      the catalytic potentials of P450s against a wide variety of compounds were
      investigated. A functionomic survey allowed the discovery of novel catalytic
      properties of P. placenta P450s. The phylogenetic diversity of the CYP53 family
      in P. placenta was clear, and CYP53D2 is capable of converting stilbene
      derivatives. This is the first report of this peculiar function of the CYP53
      family. Our increased understanding of the molecular and functional diversity of
      P450s in this fungus will facilitate comprehension of metabolic diversity in
      basidiomycetes and has future biotechnology applications.

PMID- 21938517
TI  - Safety of magnetic resonance imaging in patients with permanent pacemakers: a
      collaborative clinical approach.
AB  - OBJECTIVE: This study aimed to characterize the interactions of pacemakers with
      magnetic resonance imaging (MRI) and to identify device characteristics that
      could predict adverse interactions. BACKGROUND: The safety of MRI in patients
      with indwelling pacemaker systems remains uncertain. Previous studies
      demonstrated safety in most patients, but unpredictable, potentially concerning
      changes in pacemaker behavior have occurred. METHODS: We prospectively studied
      patients with pacemaker devices in situ who were not pacemaker dependent and in
      whom MRI was essential for adequate diagnosis and treatment. All patients were
      monitored by electrocardiography and pulse oximetry during scanning; devices were
      interrogated and cardiac enzymes were measured before and after scanning.
      RESULTS: Of 32 patients studied (46 MRI examinations), 28 patients had a dual
      chamber system and one had a biventricular device. Regions scanned were the head
      and spine. Devices were reprogrammed to asynchronous pacing or sense-only mode in
      all except six patients before MRI. During six scanning episodes (five patients),
      "power-on" resetting of the device was noted. Magnet-mode pacing was noted during
      four episodes (three patients). Occasional premature ventricular contractions
      were noted in one patient. No significant changes in battery voltage, sensed P
      wave and R wave, pacing thresholds, lead impedance, or cardiac enzymes were noted
      immediately after MRI or at 1-month follow-up. CONCLUSIONS: Overall, no
      significant changes were seen in pacemaker device function, and no adverse
      clinical events were observed. A minority of patients with older devices had
      unpredictable changes in device behavior, which stresses the need for close
      monitoring during and careful device interrogation after scanning.

PMID- 21938518
TI  - Pulmonary venous isolation versus additional substrate modification as treatment
      for paroxysmal atrial fibrillation.
AB  - BACKGROUND: Pulmonary vein isolation alone is ineffective in maintaining sinus
      rhythm in up to one third of patients with paroxysmal atrial fibrillation (AF).
      We compared pulmonary vein antral isolation plus additional limited ablation
      along the inferoposterior left atrium and epicardially within the adjacent
      coronary sinus (PVAI + CS) to pulmonary vein antral isolation (PVAI) alone in
      patients with paroxysmal AF. METHODS: Forty-two consecutive patients with
      paroxysmal AF were prospectively randomized to PVAI vs. PVAI + CS. All patients
      were seen 3, 6, 12, and 18 months after ablation and underwent 24-h ambulatory
      Holter monitoring. RESULTS: Following a single procedure, 17 out of 22 patients
      (77%) remained arrhythmia free off antiarrhythmic medication after PVAI at 18
      months vs. 10 out of 20 (50%) after PVAI + CS (p < 0.01). After PVAI, three
      patients had recurrent paroxysmal AF, and two had atrial tachycardia, whereas
      after PVAI + CS, three patients had recurrent paroxysmal AF, and seven had atrial
      tachycardia. All patients in the PVAI + CS group with atrial tachycardia who
      underwent a second procedure were found to have peri-mitral macro-reentry as the
      underlying mechanism. Eighty-one percent of patients remained arrhythmia free off
      medication after 1.09 procedures in the PVAI group vs. 80% after 1.35 procedures
      in the PVAI + CS group (p < 0.01). CONCLUSION: The addition of limited ablation
      along the inferoposterior left atrium and within the adjacent coronary sinus to
      PVAI alone did not reduce the recurrence rate of paroxysmal atrial fibrillation
      and was associated with an increased rate of peri-mitral macro-reentrant atrial
      tachycardia.

PMID- 21938519
TI  - NT-proBNP, but not ANP and C-reactive protein, is predictive of paroxysmal atrial
      fibrillation in patients undergoing pulmonary vein isolation.
AB  - OBJECTIVE: The purpose of this study is to evaluate the relationship between
      plasma high-sensitivity C-reactive protein (hs-CRP), atrial natriuretic peptides
      (ANP), N-terminal-pro-brain natriuretic peptide (NT-proBNP) levels, and the risk
      and recurrence of atrial fibrillation (AF) after pulmonary vein isolation (PVI)
      in patients with paroxysmal atrial fibrillation (PAF). METHODS: Plasma ANP, NT
      proBNP, and hs-CRP levels were measured before and 3 months after PVI in 33
      patients with PAF and 30 control participants. RESULTS: (1) NT-proBNP levels at
      baseline were significantly elevated in subjects with PAF compared with control
      subjects (296.8 +/- 272.1 vs. 80.8 +/- 69.1 pg/ml), but ANP and hs-CRP levels
      were normal; NT-proBNP levels normalized 3 months after PVI, but ANP and hs-CRP
      levels did not change significantly; NT-proBNP levels at baseline in the
      recurrent group were markedly higher than those in the nonrecurrent AF group
      (572.7 +/- 234.2 vs. 176.8 +/- 188.7 pg/ml). (2) Cox stepwise multivariate
      analysis demonstrated that only elevated NT-proBNP level at baseline was an
      independent predictor of AF recurrence (p < 0.001) after PVI among 13 variables,
      such as echocardiographic parameters, plasma ANP, NT-proBNP, and hs-CRP levels. A
      cutoff value of NT-proBNP >= 423.2 pg/ml was a significant risk factor for AF
      recurrence (p = 0.002). CONCLUSIONS: Elevated NT-proBNP level at baseline, but
      not ANP and hs-CRP, is a sensitive biomarker for early predicting AF recurrence
      in patients with PAF.

PMID- 21938520
TI  - Decreased expression of myelin gene regulatory factor in Niemann-Pick type C 1
      mouse.
AB  - Niemann-Pick type C 1 (NPC1) disease is an autosomal recessive cholesterol
      transport defect resulting in a neurodegenerative process in patients mainly at
      an early age, although some patients may start with manifestation in adult. Since
      loss of myelin is considered as a main pathogenetic factor, the precise mechanism
      inducing dysmylination in NPC1 disease is still unclear. In the present study, a
      quantitative evaluation on the myelin protein and its regulatory factors of
      oligodendrocytes, such as SRY-related HMG-box 10 (Sox10), Yin Yang 1 factor (YY1)
      and myelin gene regulatory factor (MRF), in different parts of the brain and
      spinal cord was performed in NPC1-mutant mice. The results showed that NPC1
      protein was expressed in oligodendrocytes and the amount of myelin protein was
      generally decreased in all parts of the brain and spinal cord in NPC1-mutant
      mice. Compared to wild type, the amount of Sox10 and YY1 was not different in
      NPC1-mutant mice, but MRF was significantly decreased, suggesting a possible
      mechanism perturbing differentiation of oligodendrocytes and the myelination
      process in the NPC1-mutant mouse.

PMID- 21938521
TI  - Single cysteines in the extracellular and transmembrane regions modulate pannexin
      1 channel function.
AB  - Pannexins form high-conductance ion channels in the membranes of many vertebrate
      cells. Functionally, they have been associated with multiple functional pathways
      like the propagation of calcium waves, ATP release, responses to ischemic
      conditions and apoptosis. In contrast to accumulating details which uncovered
      their functions, the molecular mechanisms for pannexin channel regulation and
      activation are hardly understood. To further elucidate regulatory mechanisms, we
      substituted cysteine residues, expected key elements for channel function, in
      extracellular and transmembrane regions of Pannexin 1 (Panx1). Most apparently,
      substitution of the transmembrane cysteine C40 resulted in constitutively open
      channels with profoundly increased activity. Hence, Xenopus laevis oocytes
      injected with corresponding cRNA showed strongly impaired viability, anomalous
      dye uptake and greatly increased whole-cell conductivity. All changes induced by
      C40 substitution were significantly reduced by the Panx1 channel blocker
      carbenoxolone, indicating that channel activity of the mutated Panx1 had been
      affected. In contrast, no changes occurred after substitution of the two other
      transmembrane cysteines, C215 and C227, in terms of channel conductivity.
      Finally, substitution of any of the four extracellular cysteines resulted in
      complete loss of channel function in both X. laevis oocytes and transfected N2A
      cells. From this, we conclude that cysteine residues of Panx1 reveal differential
      functional profiles for channel activation and drug sensitivity.

PMID- 21938522
TI  - Changing patterns of rotavirus genotypes in Turkey.
AB  - To describe the circulation dynamics of human rotavirus genotypes and to
      understand the epidemiological changes of rotavirus infection in Turkey, one of
      the countries where the highest mortality rates are seen due to rotavirus in
      Europe. Stool samples of children under 5 years of age which gave positive
      results for rotavirus antigen were stored at -20 degrees C and then genotyped
      using multiplex reverse transcription polymerase-chain reaction. Of the 494 stool
      samples, 137 (28.1%) were positive for rotavirus antigen and 100 (73%) samples
      which could be genotyped successfully were included in the study. 42 (42%)
      samples were from inpatients, and 58 (58%) were from outpatients. The median age
      of the children was 16 months (5 days-59 months). G9 and P[8] were the most
      frequent G and P genotypes, and were detected in 30 (30%) and 55 patients (55%),
      respectively. In 90 samples for which both G and P genotypes could be determined,
      34 different combinations were found. G9P[8] was the most frequent genotype
      detected in 19 patients (19%), followed by G1P[8] and G4P[6] each in 7 (7%)
      patients. The incidence of mixed infection was found to be 26%. Novel strains
      like P2A[6] and P[5] and unusual reassortant strains were detected. Distribution
      of rotavirus genotypes exhibited distinctive changes in this study. When the ever
      changing epidemiology of rotaviruses is taken into account, ongoing surveillance
      studies are important before the inclusion of rotavirus vaccines in national
      immunization program of Turkey.

PMID- 21938523
TI  - Enhanced soluble expression of a thermostable cellulase from Clostridium
      thermocellum in Escherichia coli.
AB  - In this study, the cellulase gene celD from Clostridium thermocellum was cloned
      into expression vectors pET-20b(+) and pHsh. While high expression can be
      achieved by means of both these expression systems, only the pHsh expression
      system gives soluble proteins. By weakening the mRNA secondary structure and
      replacing the rare codons for the N-terminal amino acids of the target protein,
      the expression level of CelD was increased from 4.1 +/- 0.3 to 6.4 +/- 0.4 U ml(
      1) in LB medium. Recombinant CelD was purified by heat treatment followed by Ni
      NTA affinity. The purified CelD exhibited the highest activity at pH 5.4 and 60
      degrees C, and retained more than 50% activity after incubation at 70 degrees C
      for 1 h. The cellulase activity of CelD was significantly enhanced by Ca(2+) but
      inhibited by EDTA. The favorable properties of CelD offer the potential for
      genetic modification of strains for biomass degradation. Presently, one of the
      major bottlenecks for industrial cellulase users is the high cost of enzyme
      production. The high level expression of soluble enzymes from the pHsh expression
      system offers a novel approach for the production of cellulases to be used in
      various agro-industrial processes such as chemical, food and textile.

PMID- 21938524
TI  - Multidimensional comparison of personality characteristics of the Big Five model,
      impulsiveness, and affect in pathological gambling and obsessive-compulsive
      disorder.
AB  - The phenomenological resemblance between pathological gambling (PG) and obsessive
      compulsive disorder (OCD) has led to suggestions that PG be categorized as an
      obsessive-compulsive-spectrum disorder (OCSD). This study aimed to explore
      whether PG resembles OCD in terms of personality and temperament. Fifteen
      patients with PG, 18 patients with OCD, and 33 healthy control subjects were
      included in the study. The study subjects were all male and drug naive. We
      analyzed data obtained from three self-report questionnaires assessing
      personality, impulsiveness, and affect: the short version of the NEO Personality
      Inventory-Revised (NEO-PI-R), the Barratt Impulsiveness Scale-11 (BIS-11), and
      the Positive Affect and Negative Affect Schedule (PANAS). Participants with PG
      and OCD demonstrated less conscientiousness (F = 7.089, P = .002) and less
      openness to experience (F = 6.268, P = .003) and less positive affect (F =
      15.816, P < .001) than did healthy controls. The two diagnostic groups did not
      differ from each other with respect total BIS-11 scores, but those with OCD
      showed more neuroticism than did those with PG and healthy controls ( F = 9.556,
      P < .001), and those with PG obtained higher scores on the non-planning
      impulsiveness factor of BIS-11 than did those with OCD or healthy controls ( F =
      9,835, P < .001). PG and OCD share similar profiles in terms of personality and
      temperament. This study provides phenomenological evidence supporting the
      conceptualization of PG as an OCSD.

PMID- 21938525
TI  - Inventory of the chemicals and the exposure of the workers' skin to these at two
      leather factories in Indonesia.
AB  - PURPOSE: Tannery workers are exposed to hazardous chemicals. Tannery work is
      outsourced to newly industrialized countries (NICs) where attention into
      occupational health hazards is limited. In this study, we investigated the skin
      exposure to hazardous chemicals in tannery workers and determined the prevalence
      of occupational skin diseases (OSDs) at tanneries in a NIC. METHODS: A cross
      sectional study on the observation of the working process and an inventory and
      risk assessment of the chemicals used. Classification of chemicals as potential
      sensitizers/irritants and a qualitative assessment of exposure to these
      chemicals. Workers were examined and interviewed using Nordic Occupational Skin
      Questionnaire-2002/LONG. RESULTS: The risk of OSDs at the investigated tanneries
      was mainly related to the exposure of the workers' skin to chemicals in hot and
      humid environmental conditions. In 472 workers, 12% reported a current OSD and 9%
      reported a history of OSD. In 10% of all cases, an OSD was confirmed by a
      dermatologist and 7.4% had an occupational contact dermatitis (OCD). We observed
      that personal protective equipment (PPE) used was mainly because of skin problems
      in the past and not as a primary protection against OSD. CONCLUSION: We observed
      a high frequency and prolonged exposure to many skin hazardous factors in tannery
      work although PPE was relatively easily available and which was generally used as
      a secondary preventative measure. The observed point-prevalence in this study was
      at the same level as that reported for other high-risk OSDs in Western countries
      and other tanneries in NICs. However, the observed point-prevalence in this study
      was lower than that reported in India and Korea. The results of our study and
      those of other studies at tanneries from other NICs were probably influenced by
      Healthy Worker Survivor Effect (HWSE).

PMID- 21938526
TI  - An evaluation and comparison of intraventricular, intraparenchymal, and fluid
      coupled techniques for intracranial pressure monitoring in patients with severe
      traumatic brain injury.
AB  - OBJECTIVE: Intracranial pressure measurements have become one of the mainstays of
      traumatic brain injury management. Various technologies exist to monitor
      intracranial pressure from a variety of locations. Transducers are usually placed
      to assess pressure in the brain parenchyma and the intra-ventricular fluid, which
      are the two most widely accepted compartmental monitoring sites. The individual
      reliability and inter-reliability of these devices with and without cerebrospinal
      fluid diversion is not clear. The predictive capability of monitors in both of
      these sites to local, regional, and global changes also needs further
      clarification. The technique of monitoring intraventricular pressure with a fluid
      coupled transducer system is also reviewed. There has been little investigation
      into the relationship among pressure measurements obtained from these two sources
      using these three techniques. METHODS: Eleven consecutive patients with severe,
      closed traumatic brain injury not requiring intracranial mass lesion evacuation
      were admitted into this prospective study. Each patient underwent placement of a
      parenchymal and intraventricular pressure monitor. The ventricular catheter
      tubing was also connected to a sensor for fluid-coupled measurement. Pressure
      from all three sources was measured hourly with and without ventricular drainage.
      RESULTS: Statistically significant correlation within each monitoring site was
      seen. No monitoring location was more predictive of global pressure changes or
      more responsive to pressure changes related to patient stimulation. However, the
      intraventricular pressure measurements were not reliable in the presence of
      cerebrospinal fluid drainage whereas the parenchymal measurements remained
      unaffected. CONCLUSION: Intraparenchymal pressure monitoring provides equivalent,
      statistically similar pressure measurements when compared to intraventricular
      monitors in all care and clinical settings. This is particularly valuable when
      uninterrupted cerebrospinal fluid drainage is desirable.

PMID- 21938527
TI  - Controlling the position and the dislocation of the middle ear transducer with
      high-resolution computed tomography and digital volume tomography: implications
      for the transducers' design.
AB  - A minimal tip dislocation of the middle ear transducer (MET((r)), Otologics Ltd)
      may result in poor hearing performance. Our objective was to examine if a defined
      MET dislocation can be diagnosed by high-resolution computed tomography (HRCT) or
      digital volume tomography (DVT). A human cadaver head was sequentially implanted
      with different MET tips (incus application) including a ceramic tip (T 1c), a
      titanium tip (T 1t), a new, thinner titanium tip (T 2), and a spherical titanium
      tip (Ts). HRCT and DVT studies were performed. Afterward, the tips were pulled
      back 0.5 mm, so that they were not attached to the incus. HRCT and DVT scans were
      repeated to identify the dislocation. Using the best plain in HRCT images, the
      dislocation of the transducer could be measured reliably and reproducibly in half
      of the cases. In particular, the precise positioning and the dislocation could be
      identified when T 1t and Ts were implanted, with the Ts showing the best
      visibility. DVT failed in recognizing the dislocation in all cases. The
      identification of MET tip's dislocation with HRCT depends on the shape, size, and
      material of the tip. This knowledge is useful for the design of the implants, as
      determination of the right position of the middle ear transducer may be proven
      important for the hearing outcome. In some cases, however, surgical exploration
      may still be required. Although DVT represents a promising imaging method for the
      otologists, it can barely help when MET dislocation is suspected.

PMID- 21938528
TI  - Numerical simulation of normal nasal cavity airflow in Chinese adult: a
      computational flow dynamics model.
AB  - Our purpose is to simulate the airflow inside the healthy Chinese nose with
      normal nasal structure and function by computational fluid dynamics (CFD) method
      and to analyze the relationship between the airflow and physiological function.
      In this study, we used the software MIMICS 13.0 to construct 20 3-dimensional (3
      D) models based on the computer tomography scans of Chinese adults' nose with
      normal nasal structure and function. Thereafter, numerical simulations were
      carried out using the software FLUENT 6.3. Then the characteristics of airflow
      inside the airway and sinuses were demonstrated qualitatively and quantitatively
      in steady state. We found that during the inhalation phase, the vortices and
      turbulences were located at anterior part and bottom of the nasal cavity. But
      there is no vortex in the whole nasal cavity during the expiratory phase. The
      distributions of pressure and wall shear stress are different in two phases. The
      maximum airflow velocity occurs around the plane of palatine velum during both
      inspiratory and expiratory phases. After the airflow passed the nasal valve, the
      peak velocity of inhaled airflow decreases and it increases again at the
      postnaris. Vice versa, the exhaled airflow decelerates after it passed the
      postnaris and it accelerates again at nasal valve. The data collected in this
      presentation validates the effectiveness of CFD simulation in the study of
      airflow in the nasal cavity. Nasal airflow is closely related to the structure
      and physiological functions of the nasal cavity. CFD may thus also be used to
      study nasal airflow changes resulting from abnormal nasal structure and nasal
      diseases.

PMID- 21938529
TI  - R-flurbiprofen, a novel nonsteroidal anti-inflammatory drug, decreases cell
      proliferation and induces apoptosis in pituitary adenoma cells in vitro.
AB  - R-flurbiprofen, a nonsteroidal anti-inflammatory drug derivative, has been shown
      to inhibit colonic adenoma formation in mice. We investigated the effects of R
      flurbiprofen on cell proliferation and apoptosis in pituitary adenoma cell lines.
      GH4C1 rat pituitary cell line cultures and low-passage human primary pituitary
      cell cultures were treated with varying concentrations of R-flurbiprofen (0.1-1.0
      mM). R-flurbiprofen inhibited cell proliferation in a dose-dependent fashion. A
      terminal deoxynucleotidyl transferase dUTP nick end labeling assay and chromatin
      condensation/dead cell apoptosis assay demonstrated induction of apoptosis at
      higher concentrations of R-flurbiprofen. R-flurbiprofen decreases cell
      proliferation and induces apoptosis in pituitary adenoma cells in vitro. This may
      be a potential therapy in the management of pituitary adenoma.

PMID- 21938530
TI  - Phase II study of Gleevec(r) plus hydroxyurea (HU) in adults with progressive or
      recurrent meningioma.
AB  - We prospectively evaluated the efficacy and safety of imatinib plus hydroxyurea
      in patients with progressive/recurrent meningioma. A total of 21 patients with
      progressive/recurrent meningioma were enrolled in this dual center, single-arm,
      phase II trial. All patients received 500 mg of hydroxyurea twice a day. Imatinib
      was administered at 400 mg/day for patients not on CYP3A enzyme inducing anti
      epileptic drugs (EIAEDs) and at 500 mg twice a day for patients on EIAEDs. The
      primary endpoint was progression-free survival at 6 months (PFS-6) and secondary
      endpoints were safety, radiographic response rate, and overall survival (OS).
      Best radiographic response was stable disease and was observed in 14 patients
      (67%). PFS-6 for all patients, those with grade I tumors (n = 8) and those with
      grade II or III tumors (n = 13) was 61.9, 87.5 and 46.2%, respectively. Patients
      with grade II or III tumors had poorer PFS and OS than those with grade I tumors,
      (P = 0.025 and P = 0.018) respectively. The only grade 3 or greater adverse event
      occurring in >= 10% of patients was anemia (10%). Imatinib plus hydroxyurea is
      well tolerated among patients with meningioma but has modest anti-tumor activity
      for this indication.

PMID- 21938531
TI  - Clinical outcome of central nervous system metastases from breast cancer:
      differences in survival depending on systemic treatment.
AB  - Central nerve system (CNS) metastases are a feared complication of breast cancer
      and are associated with poor prognosis. The purpose of this study is to
      investigate the clinical characteristics of CNS metastases and to clarify the
      prognostic factors after CNS metastases in breast cancer at a single institution
      over a long time period. We retrospectively reviewed the medical records of
      breast cancer patients diagnosed at Seoul National University Hospital from 1981
      to 2009 and identified the patients who experienced CNS metastases. We collected
      the data, including demographics, clinico-pathologic characteristics, dates of
      diagnosis of original breast cancer and subsequent metastases, and date of death,
      and correlated the findings with the clinical outcome. A total of 400 patients
      were identified, of whom 17 (4.3%) were diagnosed with CNS metastases and primary
      breast cancer concurrently and 383 (95.7%) experienced CNS metastases subsequent
      to the diagnosis of primary breast cancer. Further, 318 patients (79.5%) had only
      brain parenchymal metastases, 30 (7.5%) had only leptomeningeal metastases, and
      52 (13%) had both. After the diagnosis of CNS metastasis, 170 patients (42.5%)
      received systemic chemotherapy (CTx) and 143 (35.8%) received CTx after whole
      brain radiation therapy (WBRT). The patients with good performance status (PS),
      initial CNS metastasis as recurrence, absence of extracranial metastases, non
      visceral extracranial metastases, longer interval from the date of primary breast
      cancer to the date of CNS metastasis, and CTx after WBRT and gamma-knife surgery
      (GKS), had better outcomes in univariate analyses. In multivariate analysis, good
      PS, systemic CTx after WBRT, GKS, and longer interval to CNS metastasis, were
      independent prognostic factors for overall survival after CNS metastases. Our
      results suggest that appropriate palliative systemic therapy after WBRT or GKS,
      and adequate palliative treatment via combined modalities are helpful for breast
      cancer patients, even after the detection of CNS metastases.

PMID- 21938532
TI  - New definition for periprosthetic joint infection: from the Workgroup of the
      Musculoskeletal Infection Society.

PMID- 21938533
TI  - The Classic: A Dissertation Upon Dislocations and Fractures of the Clavicle and
      Shoulder-Joint. 1894.

PMID- 21938534
TI  - Biographical sketch: Thomas Callaway, FRCS (1822-1869).
AB  - This biographical sketch on Thomas Callaway corresponds to the historic text, The
      Classic: A Dissertation Upon Dislocations and Fractures of the Clavicle and
      Shoulder-Joint (1849) available at DOI 10.1007/s11999-011-2098-1 .

PMID- 21938535
TI  - The use of three strategies to improve quality of care at a national level.
AB  - BACKGROUND: Improving the quality of care is essential and a priority for
      patients, surgeons, and healthcare providers. Strategies to improve quality have
      been proposed at the national level either through accreditation standards or
      through national payment schemes; however, their effectiveness in improving
      quality is controversial. QUESTIONS/PURPOSES: The purpose of this review was to
      address three questions: (1) does pay-for-performance improve the quality of
      care; (2) do surgical safety checklists improve the quality of surgical care; and
      (3) do practice guidelines improve the quality of care? These three strategies
      were chosen because there has been some research assessing their effectiveness in
      improving quality, and implementation had been attempted on a large scale such as
      entire countries. METHODS: We performed a literature review from 1950 forward
      using Medline to identify Level I and II studies. We evaluated the three
      strategies and their effects on processes and outcomes of care. When possible, we
      examined strategy implementation, patients, and systems, including provider
      characteristics, which may affect the relationship between intervention and
      outcomes with a focus on factors that may have influenced effect size. RESULTS:
      Pay-for-performance improved the process and to a lesser extent the outcome of
      care. Surgical checklists reduced morbidity and mortality. Explicit practice
      guidelines influenced the process and to a lesser extent the outcome of care.
      Although not definitively showed, clinician involvement during development of
      intervention and outcomes, with explicit strategies for communication and
      implementation, appears to increase the likelihood of positive results.
      CONCLUSION: Although the cost-effectiveness of these three strategies is unknown,
      quality of care could be enhanced by implementing pay-for-performance, surgical
      safety checklists, and explicit practice guidelines. However, this review
      identified that the effectiveness of these strategies is highly context-specific.

PMID- 21938536
TI  - Seasonal variation of HUS occurrence and VTEC infection in children with acute
      diarrhoea from Argentina.
AB  - In order to study the seasonality of haemolytic uraemic syndrome (HUS) and
      verotoxigenic Escherichia coli (VTEC) infection in children, 437 patients under 6
      years of age with acute diarrhoea were studied, 8% of whom progressed to HUS.
      VTEC was found in 10% of all of the stool samples analysed and seasonal
      occurrence of HUS (p < 0.01) was confirmed. VTEC infection was more prevalent in
      warm months, although the differences were not statistically significant.
      Moreover, a significant difference in the detection of O157:H7 serotype and in
      the vt profile between cold and warm months (autumn and winter; spring and
      summer, respectively) was established. The O157:H7 serotype was isolated more
      frequently during warm months. Moreover, a predominance of vt (2) was noted,
      which was partially replaced by the combination of vt (1) with vt (2) in the cold
      season. The results of this study indicate the seasonal variation of the disease
      and the presence of serotype O157:H7 and the vt types. They also reinforce the
      need to develop prevention programmes considering the seasonal pattern of the
      disease, which would generate an impact on public health. Control strategies of
      the pathogen in cattle in the most risky season of the year would also be of
      benefit.

PMID- 21938537
TI  - A large outbreak of Opisthorchis felineus in Italy suggests that opisthorchiasis
      develops as a febrile eosinophilic syndrome with cholestasis rather than a
      hepatitis-like syndrome.
AB  - We describe the greatest Italian human acute opisthorchiasis outbreak acquired
      from eating raw tenches. Out of 52 people with suspected opisthorchiasis, 45
      resulted in being infected. The most frequent symptoms and laboratory findings
      were fever, abdominal pain and eosinophilia. Seven tri-phasic computed tomography
      (CT) scans were done, showing multiple hypodense nodules with hyper-enhancement
      in the arterial phase. All patients took one day of praziquantel 25 mg/kg TID
      without failures. Reported symptoms suggested a febrile eosinophilic syndrome
      with cholestasis rather than a hepatitis-like syndrome. It seems common to find
      hepatic imaging alterations during acute opisthorchiasis: CT scan could be the
      most suitable imaging examination. Even if stool test remains the diagnostic gold
      standard, we found earlier positivity with the serum antibody test. Without
      previous freezing, the consumption of raw freshwater fish should be avoided.

PMID- 21938538
TI  - Characterization of IncA/C conjugative plasmid harboring bla TEM-52 and bla CTX-M
      15 extended-spectrum beta-lactamases in clinical isolates of Escherichia coli in
      Tunisia.
AB  - To characterize the extended-spectrum beta-lactamases (ESBLs) as well as their
      genetic environment in different isolates of Escherichia coli from patients with
      repeated urinary tract infections, large multidrug resistance (MDR) plasmids have
      been found. Definitive evidence for the presence of an A/C incompatibility
      complex (IncA/C) plasmid in the MDR isolates was provided by the probing of
      plasmids extracted from the clinical isolates. Conjugation experiments showed
      that bla genes were transferred by conjugation from the ten E. coli clinical
      isolates to E. coli XL1-Blue recipient. A comparative restriction fragment length
      polymorphism (RFLP) analysis of these plasmids showed that they are genetically
      similar, while the overall similarity of these plasmids supports the likelihood
      of recent movements among these E. coli isolates. Polymerase chain reaction (PCR)
      amplification and sequencing of the amplicons showed that the IncA/C plasmids
      harbor two ESBLs, identified as TEM-52 and CTX-M-15. Analysis of the plasmid DNA
      surrounding the bla (CTX-M-15) gene in the clinical isolates under study revealed
      a partially truncated fragment of ISEcp1 tnpA transposase. This result indicates
      the variety of genetic events that have enabled associations between ISEcp1
      sequences and bla (CTX-M-15) genes in these clinical isolates.

PMID- 21938539
TI  - A multiplex, internally controlled real-time PCR assay for detection of toxigenic
      Clostridium difficile and identification of hypervirulent strain 027/ST-1.
AB  - The purpose of this study was to validate a multiplex real-time PCR assay capable
      of detecting toxigenic Clostridium difficile and simultaneously identifying C.
      difficile ribotype 027/ST-1 by targeting the toxin genes tcdA, tcdB and cdtA in
      one reaction and in a separate reaction identifying the Delta117 deletion in tcdC
      associated with ribotype 027/ST-1. PCR was done prospectively on 704 samples
      routinely submitted to our department and results were compared to results of
      toxigenic culture. Sequencing of tcdC, multi locus sequence typing (MLST) and PCR
      ribotyping were done on cultured isolates to confirm the correct identification
      of the Delta117 deletion in tcdC and C. difficile ribotype 027/ST-1,
      respectively. The PCR assay displayed a sensitivity, specificity, PPV and NPV of
      99.0%, 97.4%, 87.4% and 99.8%, respectively, compared to toxigenic culture on 665
      samples evaluable both by PCR and culture. Sequencing of tcdC, ribotyping and
      MLST of cultured isolates validated the genotyping assay and confirmed the
      ability of the assay to correctly identify C. difficile ribotype 027/ST-1 in our
      current epidemiological setting. We describe the use of a combination of two
      separate PCR assays for sensitive and specific detection of toxigenic C.
      difficile and presumptive identification of C. difficile 027/ST-1.

PMID- 21938540
TI  - Absence of the right pulmonary artery associated with a partial anomalous
      pulmonary venous connection.
AB  - Unilateral absence of a pulmonary artery is a rare anomaly. Patients may present
      with hemoptysis, recurrent respiratory infections, pulmonary hypertension, or
      congestive heart failure. This report describes the case of a missing right
      pulmonary artery associated with anomalous left pulmonary venous connection not
      previously described in the medical literature.

PMID- 21938541
TI  - Fontan operation, vasopressin and septic shock: a case report on the usual
      treatment in a peculiar setting.

PMID- 21938542
TI  - Biomarker assessment of toxicity with miniaturised bioassays: diclofenac as a
      case study.
AB  - The development of suitable biomarker-based microbioassays with model species
      with ecological relevance would help increase the cost-efficiency of routine
      environmental monitoring and chemical toxicity testing. The anti-inflammatory
      drug diclofenac has been widely reported in the environment but ecotoxicological
      data are scarce. The aim of this work is to assess the acute and chronic
      sublethal toxicity of diclofenac in relevant taxa of aquatic and riparian
      ecosystems (the fish Danio rerio and the fern Polystichum setiferum). Reliable
      biomarkers of cell viability (mitochondrial activity), plant physiology
      (chlorophyll), growth (DNA content) or oxidative damage (lipid peroxidation) were
      assessed as sensitive endpoints of toxicity. DNA quantification shows that
      diclofenac induces acute lethal phytotoxicity at 24 and 48 h (LOECs 30 and 0.3
      MUg l(-1), respectively). Hormetic effects in mitochondrial activity in spores of
      Polystichum setiferum mask lethality, and adverse effects are only observed at 48
      h (LOEC 0.3 MUg l(-1)). In chronic exposure (1 week) LOEC for DNA is 0.03 MUg l(
      1). Mitochondrial activity shows a strong hormetic stimulation of the surviving
      spore population (LOEC 0.3 MUg l(-1)). Little changes are observed in chlorophyll
      autofluorescence (LOEC 0.3 MUg l(-1)). A very short exposure (90 min) of
      zebrafish embryos induces a reduction of lipid peroxidation at 0.03 MUg l(-1).
      Environmental concentrations of diclofenac can be deleterious for the development
      of significant populations of sensitive individuals in aquatic and riparian
      ecosystems.

PMID- 21938543
TI  - Salsalate improves glycemic control in patients with newly diagnosed type 2
      diabetes.
AB  - Chronic inflammation contributes to insulin resistance and type 2 diabetes
      mellitus (T2DM). We investigated whether treatment with salsalate, an anti
      inflammatory medication, improves glycemia in a group of newly diagnosed drug
      naive patients with T2DM. The study was a randomized, double-blind, placebo
      controlled trial. Diagnosis of T2DM was made within 2 months of enrollment, and
      participants had not received any anti-glycemic agent. Sixty adults were
      randomized to receive salsalate (3 g/day) or placebo for 12 weeks. Fasting plasma
      glucose and insulin, glucose 2 h after 75 g oral glucose, HbA1C, lipid profile,
      HOMA-IR, and HOMA-B were determined before and after treatment. Salsalate reduced
      fasting glucose from 6.3 +/- 0.2 mmol/l to 5.4 +/- 0.2 mmol/l (P < 0.01) and TG
      from 1.9 +/- 0.2 mmol/l to 1.5 +/- 0.2 mmol/l (P < 0.03). Fasting insulin levels
      were increased in the salsalate group from 18.8 +/- 1.6 to 21.6 +/- 3.9, while
      they decreased in the placebo group. HbA1c rose in the placebo group from 6.2% +/
      0.2 to 7.9% +/- 1.1 mmol/mol, but decreased in the intervention group from 6.1%
      +/- 0.5 to 5.6% +/- 0.2 mmol/mol (P < 0.04 for between-group comparison). HOMA-IR
      did not change but HOMA-B increased ~1.7-fold (P = 0.06) in the salsalate group.
      The results show that salsalate is effective in improving glycemic control in
      newly diagnosed naive patients with T2DM. The optimal duration of treatment with
      salsalate and sustainability of its effect requires further study
      (IRCT138709011465N1).

PMID- 21938544
TI  - An investigation into manual asymmetries in grasp behavior and kinematics during
      an object manipulation task.
AB  - Manual asymmetries in the control of movements have been investigated in a
      variety of experimental paradigms. Initial studies demonstrated that the dominant
      right hand has advantages over the non-dominant left hand in many aspects of
      motor control. However, more recent studies have shown that the presence and
      extent of these asymmetries depends on the task context and accuracy demands.
      Typically, manual asymmetries on a motor planning and motor execution level are
      examined separately. However, given that recent research has demonstrated that
      specific task constraints do not influence both levels equally, the purpose of
      the present experiment was to investigate manual asymmetries in motor planning
      and execution. To this end, initial grasp behavior (motor planning) and
      kinematics (motor execution) were examined in thirteen right-handed participants
      during a unimanual grasping and placing task. We specifically manipulated
      grasping hand, target location, object end orientation, and object grasp time at
      the start location. There were three main findings. First, motor planning or
      movement execution was similar regardless of grasping hand. Second, prospectively
      planned actions were influenced by target location and the required end
      orientation of the object. Third, the amount of time spent in an initial posture
      did not influence initial grasp postures. However, it did alter the movement
      kinematics during the grasping (approach phase) and placing (transport phase)
      portion of the task. We posit that grasping and placing movements are comprised
      of an initial grasp and a transport component, which are differentially
      influenced by task constraints.

PMID- 21938545
TI  - An open-label study to describe pharmacokinetic parameters of erlotinib in
      patients with advanced solid tumors with adequate and moderately impaired hepatic
      function.
AB  - PURPOSE: To compare the pharmacokinetic (PK) parameters of a single dose of
      erlotinib in cancer patients with moderate hepatic impairment (MHI) to those of
      cancer patients with adequate hepatic function (AHF). METHODS: Cancer patients
      with either AHF or MHI were treated with a single 150 mg dose of erlotinib on day
      1 only followed by 96 h of plasma sampling for PK assessment. From day 5,
      patients were allowed to continue daily erlotinib in a maintenance phase. Non
      smoking patients were stratified into an AHF cohort (total bilirubin <= upper
      limit of normal [ULN] and ALT/AST <= 1.5 X ULN) or a MHI cohort (Child-Pugh score
      of 7-9). The frequency of adverse events and laboratory changes were assessed.
      RESULTS: Thirty-six patients, 21 with AHF and 15 with MHI, received at least one
      dose of erlotinib. The PK of erlotinib was similar between the two cohorts with a
      median C (max) of 1.09 versus 0.828 MUg/mL and corresponding median AUC(0-t )
      29.3 versus 30.5 MUg h/mL for the AHF and MHI cohorts, respectively. Adverse
      events from erlotinib in cancer patients with MHI were consistent with the known
      safety profile. CONCLUSIONS: The PK and safety profiles of erlotinib in patients
      with MHI were similar to those with AHF. As a result, a reduced starting dose of
      erlotinib in patients with MHI is not required and treatment should be guided by
      patients' tolerability.

PMID- 21938546
TI  - Individual differences in behavioral estimates of cochlear nonlinearities.
AB  - Psychophysical methods provide a mechanism to infer the characteristics of
      basilar membrane responses in humans that cannot be directly measured. Because
      these behavioral measures are indirect, the interpretation of results depends on
      several underlying assumptions. Ongoing uncertainty about the suitability of
      these assumptions and the most appropriate measurement and compression estimation
      procedures, and unanswered questions regarding the effects of cochlear hearing
      loss and age on basilar membrane nonlinearities, motivated this experiment. Here,
      estimates of cochlear nonlinearities using temporal masking curves (TMCs) were
      obtained in a large sample of adults of various ages whose hearing ranged from
      normal to moderate cochlear hearing loss (Experiment 1). A wide range of
      compression slopes was observed, even for subjects with similar ages and
      thresholds, which warranted further investigation (Experiment 2). Potential
      sources of variance contributing to these individual differences were explored,
      including procedural-related factors (test-retest reliability, suitability of the
      linear-reference TMC, probe sensation levels, and parameters of TMC fitting
      algorithms) and subject-related factors (age and age-related changes in temporal
      processing, strength of cochlear nonlinearities estimated with distortion-product
      otoacoustic emissions, estimates of changes in cochlear function from damage to
      outer hair cells versus inner hair cells). Subject age did not contribute
      significantly to TMC or compression slopes, and TMC slopes did not vary
      significantly with threshold. Test-retest reliability of TMCs suggested that TMC
      masker levels and the general shapes of TMCs did not change in a systematic way
      when re-measured many weeks later. Although the strength of compression decreased
      slightly with increasing hearing loss, the magnitude of individual differences in
      compression estimates makes it difficult to determine the effects of hearing loss
      and cochlear damage on basilar membrane nonlinearities in humans.

PMID- 21938547
TI  - The PWC170: comparison of different stage lengths in 11-16 year olds.
AB  - It is unknown how the estimation of aerobic fitness in children and adolescents
      compares among physical working capacity (PWC) protocols with different stage
      lengths. The purpose of this study was twofold: (1) compare PWC tests with 2-, 3
      , and 6-min stage lengths in youth, and (2) examine the relationship between PWC
      at a heart rate (HR) of 170 beats min(-1) (PWC170) and peak oxygen consumption
      (VO(2)peak). Fifty youth (31 m, 19 f), aged 11-16 years participated. Each
      participant visited the laboratory twice and performed three PWC tests (2-, 3-, 6
      min stages) on a cycle ergometer. Tests usually consisted of three stages of
      increasing loads with the goal of reaching HR >= 165 beats min(-1). Individual
      regression lines were created to predict workload at HR = 170 beats ? min(-1) for
      each test. Participants completed two VO(2peak) tests, both running and cycling.
      Repeated measures ANOVA was used to compare PWC170 values. Pearson correlation
      was used to assess the relationships between VO(2peak) and power output for
      different PWC170 stage lengths. The three PWC170 protocols differ significantly;
      therefore, it is not advisable to directly compare results from different
      protocols. Furthermore, PWC170 showed moderate associations with VO(2peak), with
      the 2-min protocol showing the best correlation.

PMID- 21938548
TI  - Helicobacter pylori management in primary care.

PMID- 21938549
TI  - Avascular necrosis in HIV.
AB  - Avascular necrosis (AVN) is an emerging complication of HIV infection. The
      incidence of AVN in HIV patients is greater than the general population. Although
      the incidence has increased in the HAART era, the aetiology remains unclear. We
      report our experience of AVN from our tertiary referral HIV centre and evaluate
      risk factors for its development. Review of MRI reports of HIV-positive patients
      between 2007 and 2010 identified 22 patients with AVN (19 men, 3 women). Case
      notes and electronic records were reviewed. Twenty-two patients developed AVN,
      among 6,487 HIV patients attending our centre (0.34% incidence; 95% CI, 0.2
      0.48%). 68% of patients had multi-joint involvement. The median nadir CD4 count
      was 52 cells/MUL. 73% of patients had more than two risk factors including HAART
      (91%), protease inhibitors (68%), hypercholesterolaemia (59%), corticosteroids
      (55%), hypertriglyceridaemia (45%), smoking (45%), alcohol (27%) and CD4 <200
      cells/MUL (23%). 9% were idiopathic. AVN is an important musculoskeletal
      manifestation of HIV and may be multi-focal with multi-factorial aetiology.
      Preventative strategies should focus on risk factor modification. When
      investigating joint pain in HIV-infected patients, clinicians should maintain a
      high index of suspicion for AVN. Unexplained AVN, particularly if multi-focal,
      should prompt consideration of HIV testing.

PMID- 21938550
TI  - Low influenza vaccination rates among child care workers in the United States:
      assessing knowledge, attitudes, and behaviors.
AB  - Influenza can spread quickly among children and caregivers in child day care
      settings. Vaccination is the most effective method to prevent influenza. We
      determined 2009 pandemic influenza A (H1N1) (pH1N1) and seasonal influenza
      vaccination rates during the 2009-2010 influenza season among child care center
      employees, assessed knowledge and attitudes regarding the vaccines, and
      determined factors associated with vaccine receipt. Using a cross-sectional study
      design, from January 30-March 1, 2010, we surveyed 384 (95%) of 403 employees at
      32 licensed child centers in the United States about personal and work
      characteristics, vaccine receipt, and knowledge and attitudes regarding each
      vaccine. Forty-five (11%) and eighty five (22%) respondents reported receiving
      the pH1N1 and seasonal influenza vaccines, respectively. The most common reasons
      cited for not getting either vaccine were "I don't think I need the vaccine," "I
      don't think the vaccine will keep me from getting the flu," and "the vaccine is
      not safe." Factors independently associated with receipt of either vaccine
      included belief in its efficacy, having positive attitudes towards it, and
      feeling external pressure to get it. Child care center employees had low rates of
      pH1N1 and seasonal influenza vaccination largely due to misconceptions about the
      need for and efficacy of the vaccine. Public health messages should address
      misconceptions about vaccines, and employers should consider methods to maximize
      influenza vaccination of employees as part of a comprehensive influenza
      prevention program.

PMID- 21938551
TI  - Salamandra salamandra (Amphibia: Caudata: Salamandridae) in Portugal: not all
      black and yellow.
AB  - The fire salamander complex is quite diverse in the Iberian Peninsula where nine
      subspecies of Salamandra salamandra are currently recognized. Here, we analysed
      the geographical distribution of the subspecies S. s. gallaica and S. s. crespoi
      using partial sequences of the mitochondrial cytochrome b gene of 168 individuals
      from 12 locations in Portugal. Our results support the existence of a deep
      lineage divergence between the two subspecies, with non-overlapping geographical
      distributions except in two contact zones: one in Sesimbra on the western coast,
      and another in Alcoutim on the southeastern border with Spain. Moreover, S. s.
      crespoi displays signs of gene flow among the sampled locations whereas S. s.
      gallaica shows evidence of some restriction to gene flow. Present-day genetic
      make-up of S. s. gallaica and S. s. crespoi is a result of past historical
      events, fine-tuned by contemporary Iberian geoclimate. Humid mountain areas were
      found to harbour increased genetic diversity possibly acting as past refugia
      during drier interglacial periods. To analyse wider geographical patterns and
      lineage splitting events within S. salamandra we performed a Bayesian dating
      analysis completing our data set with previously published sequences. The
      observed divergences were associated to successive biogeographic scenarios, and
      to other Iberian species showing similar trends.

PMID- 21938552
TI  - Mechanisms of VEGF- and glutamate-induced inhibition of osmotic swelling of
      murine retinal glial (Muller) cells: indications for the involvement of vesicular
      glutamate release and connexin-mediated ATP release.
AB  - We determined the mechanisms of glutamate and ATP release from murine retinal
      glial (Muller) cells by pharmacological manipulation of the vascular endothelial
      growth factor (VEGF)- and glutamate-induced inhibition of cellular swelling under
      hypoosmotic conditions. It has been shown that exogenous glutamate inhibits
      hypoosmotic swelling of rat Muller cells via the induction of the release of ATP
      (Uckermann et al. in J Neurosci Res 83:538-550, 53). VEGF was shown to inhibit
      hypoosmotic swelling of rat Muller cells by inducing the release of glutamate
      (Wurm et al. in J Neurochem 104:386-399, 55). The swelling-inhibitory effect of
      VEGF in murine Muller cells was blocked by an inhibitor of vesicular exocytosis,
      by a modulator of the allosteric site of vesicular glutamate transporters, and by
      inhibitors of phospholipase C and protein kinase C. The swelling-inhibitory
      effect of glutamate in murine Muller cells was prevented by inhibitors of
      connexin hemichannels. The effects of both VEGF and glutamate were blocked by
      tetrodotoxin and by an inhibitor of T-type voltage-gated calcium channels. Murine
      Muller cells display connexin-43 immunoreactivity. The data suggest that Muller
      cells of the murine retina may release glutamate by vesicular exocytosis, whereas
      ATP is released through connexin hemichannels.

PMID- 21938554
TI  - Misdiagnosis of gossypiboma as hydatid cyst.

PMID- 21938553
TI  - FABP7 expression in normal and stab-injured brain cortex and its role in
      astrocyte proliferation.
AB  - Reactive gliosis, in which astrocytes as well as other types of glial cells
      undergo massive proliferation, is a common hallmark of all brain pathologies.
      Brain-type fatty acid-binding protein (FABP7) is abundantly expressed in neural
      stem cells and astrocytes of developing brain, suggesting its role in
      differentiation and/or proliferation of glial cells through regulation of lipid
      metabolism and/or signaling. However, the role of FABP7 in proliferation of glial
      cells during reactive gliosis is unknown. In this study, we examined the
      expression of FABP7 in mouse cortical stab injury model and also the phenotype of
      FABP7-KO mice in glial cell proliferation. Western blotting showed that FABP7
      expression was increased significantly in the injured cortex compared with the
      contralateral side. By immunohistochemistry, FABP7 was localized to GFAP(+)
      astrocytes (21% of FABP7(+) cells) and NG2(+) oligodendrocyte progenitor cells
      (62%) in the normal cortex. In the injured cortex there was no change in the
      population of FABP7(+)/NG2(+) cells, while there was a significant increase in
      FABP7(+)/GFAP(+) cells. In the stab-injured cortex of FABP7-KO mice there was
      decrease in the total number of reactive astrocytes and in the number of BrdU(+)
      astrocytes compared with wild-type mice. Primary cultured astrocytes from FABP7
      KO mice also showed a significant decrease in proliferation and omega-3 fatty
      acid incorporation compared with wild-type astrocytes. Overall, these data
      suggest that FABP7 is involved in the proliferation of astrocytes by controlling
      cellular fatty acid homeostasis.

PMID- 21938555
TI  - Low-intensity pulsed ultrasound reduces the inflammatory activity of synovitis.
AB  - The purpose of this study was to examine the effect of low-intensity pulsed
      ultrasound (LIPUS) on the cell proliferation and growth of synovial membrane
      cells stimulated with inflammatory cytokines, and to evaluate the effectiveness
      of LIPUS treatment of synovitis in the knee joints of animal models for
      rheumatoid arthritis. The rabbit knee synovial membrane cell line, HIG-82, was
      cultured in medium with or without IL-1beta or TNF-alpha. Four hours after
      stimulation with the cytokines, the cells received LIPUS or sham exposure. Cell
      proliferation and growth were then analyzed. Using MRL/lpr mice, the anti
      inflammatory effects of LIPUS were also evaluated in vivo. Stimulation with
      proinflammatory cytokines significantly up-regulated cell proliferation which was
      significantly down-regulated by LIPUS exposure. In MRL/lpr mice, exposure of knee
      joints to LIPUS caused a significant reduction of histological damage compared to
      the control. Histological lesions were significantly reduced in the joints
      treated with LIPUS for 3 weeks. Cox-2-positive cells in the knee joints treated
      with LIPUS were markedly decreased compared to the control joints. Therefore,
      LIPUS stimulation may be a medical treatment for joint inflammatory diseases,
      such as synovitis.

PMID- 21938556
TI  - Paraneoplastic encephalomyelopathies: pathology and mechanisms.
AB  - The last three decades have seen major advances in the understanding of
      paraneoplastic and idiopathic autoimmune disorders affecting the central nervous
      system (CNS). Neural-specific autoantibodies and their target antigens have been
      discovered, immunopathology and neuroimaging patterns recognized and pathogenic
      mechanisms elucidated. Disorders accompanied by autoantibody markers of neural
      peptide-specific cytotoxic effector T cells [such as anti-neuronal nuclear
      antibody type 1 (ANNA-1, aka anti-Hu), Purkinje cell antibody type 1 (PCA-1, aka
      anti-Yo) and CRMP-5 IgG] are generally poorly responsive to immunotherapy.
      Disorders accompanied by neural plasma membrane-reactive autoantibodies [the
      effectors of synaptic disorders, which include antibodies targeting voltage-gated
      potassium channel (VGKC) complex proteins, NMDA and GABA-B receptors] generally
      respond well to early immunotherapy. Here we describe in detail the
      neuropathological findings and pathophysiology of paraneoplastic CNS disorders
      with reference to antigen-specific serology and neurological and oncological
      contexts.

PMID- 21938557
TI  - Expression and clinical significance of CK19 and CK20 expressions in transverse
      mesocolon biopsies from patients with gastric carcinoma.
AB  - We sought to evaluate in this study the significance of cytokeratin (CK)-19 and
      CK-20 in determining the peritoneal micrometastasis of gastric carcinoma and also
      determine the factors related with the occurrence of peritoneal micrometastasis.
      For this purpose, 152 patients with gastric cancer were enrolled in the study and
      transverse mesocolon biopsies were undertaken intraoperatively. The CK19 and CK20
      immunohistochemical staining were performed on the tissue samples, and the
      results were compared with those of H&E staining and peritoneal lavage cytology
      (PLC). Our data show that the positivity rates of CK19 and CK20 in transverse
      mesocolon were 48.6 and 61.2%, respectively, which were significantly higher (P <
      0.05) than that (10.0%) of PLC. Besides, the positivity rate increased with the
      depth of tumor invasion. Based on these data, we concluded that CK19 and CK20
      expressions could be adopted to determine the peritoneal micrometastasis for
      accurate clinical staging of the patients. These data provide reliable guideline
      for postoperative treatment and prognosis of gastric carcinoma.

PMID- 21938558
TI  - Electrophysiologic characteristics of the Crista terminalis and implications on
      atrial tachycardia in rabbits.
AB  - The objective of this study was to evaluate the electrophysiologic
      characteristics of Crista terminalis (CT) and their implication in the
      pathogenesis of atrial tachycardia in rabbits. For this purpose, 27 New Zealand
      rabbits were used. Using standard glass microelectrode technique, cellular action
      potentials (APs) of CT and pectinate muscle (PM) were recorded in normal Tyrode's
      perfusion and Tyrode's perfusion with 4 MUM isoproterenol. Longitudinal
      conduction velocity (V(L)) and transverse conduction velocity (V(T)) of CT were
      measured. As our data show, CT tissue had a trend of spontaneous phase IV
      depolarization. Conduction anisotropy (V(L)/V(T)) of CT was 4.53 +/- 0.91. The
      duration of the AP of CT was longer than that of PM cells. APD(20) and APD(90)
      for CT were 28.1 +/- 3.5 and 145.3 +/- 7.1 ms; and for PM cells were 21.8 +/- 4.1
      and 125.3 +/- 6.3 ms, respectively (all P values < 0.01). The early and delayed
      action depolarizations were recorded after isoproterenol perfusion. A fast
      paroxysmal irregular rhythm was recorded which could be arrested by 0.1 mmol/l
      Isoptin. It was, therefore, concluded that the latent autorhythmicity, trigger
      activity, and conduction properties of CT might provide the electrophysiologic
      basis for the occurrence and sustenance of atrial arrhythmia.

PMID- 21938559
TI  - Defining a high-risk subgroup of pathological T2N0 gastric cancer by prognostic
      risk stratification for adjuvant therapy.
AB  - BACKGROUND: Adjuvant therapy is not usually recommended in AJCC T2N0M0 gastric
      cancer, yet sometimes is indicated for high-risk patients. The purpose of this
      study is to stratify the risk of pathological T2N0 gastric cancer after
      gastrectomy based on clinicopathological factors so as to predict prognosis and
      guide treatment. METHODS: We analyzed our documented clinical database of 233
      patients with T2N0M0 gastric cancer who underwent radical resection between 2000
      and 2007. No adjuvant chemotherapy was applied. RESULTS: For the entire study
      group, the overall 5-year survival rate was 88.5%. Multivariate analysis
      indicated there were three tumor characteristics which were independent
      prognostic factors: lymphatic and/or blood vessel invasion (p = 0.025), tumor
      diameter (p = 0.004), and perineural invasion (p = 0.009). Three risk groups were
      created based on weighted variables with overall 5-year survival of 97.7%, 83%,
      and 50.3% as low-risk, intermediate-risk, and high-risk groups, respectively (p <
      0.001). CONCLUSION: Patients with T2N0 gastric cancer have a favorable prognosis
      after radical resection. A prognostic risk model of patients with pT2N0 gastric
      cancer undergoing radical resection is constructed based on lymphatic and/or
      blood vessel invasion, tumor diameter, and perineural invasion. The prognostic
      risk model identifies a small subgroup of patients with an increased risk of
      death, suggesting adjuvant therapy may be considered for these patients.

PMID- 21938560
TI  - Perioperative outcomes for open distal pancreatectomy: current benchmarks for
      comparison.
AB  - BACKGROUND: Open distal pancreatectomy (ODP) outcomes have largely relied on
      single-institution data from high-volume, tertiary centers. To provide
      contemporary, national benchmarks of ODP outcomes, we examined the American
      College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP)
      database. METHODS: Using the ACS-NSQIP database (2005-2007), we identified 868
      cases of ODP. Operative time, intraoperative transfusion, and length-of-stay
      (LOS) data were compiled. Univariate and multivariate analyses were performed
      adjusting for age, body mass index, diagnosis, creatinine, albumin, hematocrit,
      and American Society of Anesthesiologists (ASA) classification for likelihood of
      any postoperative complication and severe complication (composite endpoint: organ
      space surgical site infection, reoperation, or death). RESULTS: Thirty-day
      overall complication, severe complication, and mortality rates were 27.2%, 11.6%,
      and 1%, respectively. Mean operative time was 206 min (+/-86), 18.1% patients
      required intraoperative red blood cell transfusion (median 2 units), and median
      LOS was 6 days. Predictors of any complication or severe complication were renal
      insufficiency, hypoalbuminemia, and worsening ASA classification. Malignant
      diagnosis was not associated with poorer outcomes. DISCUSSION: ODP remains the
      gold standard for lesions of the pancreatic body or tail. The current analysis
      reflects nationwide data that may serve as current benchmarks for both open and
      laparoscopic techniques.

PMID- 21938561
TI  - Gene variation, population differentiation, and sociogenetic structure of nests
      of Partamona seridoensis (Hymenoptera: Apidae, Meliponini).
AB  - Gene variation and the differentiation of two populations of Partamona
      seridoensis (Hymenoptera: Apidae: Meliponini) from the Caatinga biome, a semiarid
      ecosystem unique to Brazil, were estimated through allozymic and microsatellite
      analyses. These populations exhibited similar low degrees of enzyme gene
      variation. Observed genotype frequencies at the allozyme and microsatellite loci
      were in accordance with Hardy-Weinberg equilibrium in the two populations. Both
      markers demonstrated that the two populations are not genetically homogeneous and
      must be considered distinct populations. The occurrence of private alleles at the
      allozyme and microsatellite loci corroborates this differentiation, sustaining
      the hypothesis of a low level of interpopulation gene flow. The phenotypic
      segregations clearly demonstrated that the progeny inside each nest were the
      result of mating between the queen of the colony and only one male.

PMID- 21938562
TI  - Comparative assessment of genetic variability in the populations of endemic and
      endangered yellow catfish, Horabagrus brachysoma (Teleostei: Horabagridae), based
      on allozyme, RAPD, and microsatellite markers.
AB  - The comparative assessment of genetic diversity using allozymes, random amplified
      polymorphic DNA (RAPD), and microsatellite markers was conducted in endemic and
      endangered yellow catfish (Horabagrus brachysoma) sampled from three locations in
      Western Ghats river systems of India. Among the three markers, microsatellites
      show more polymorphism, having 100% polymorphic loci, whereas allozymes show the
      least (56%). In RAPD, 60.5% of fragments were polymorphic. Observed
      heterozygosity and F(ST) values were very high in microsatellites, compared with
      the other markers. Microsatellite and RAPD markers reported a higher degree of
      genetic differentiation than allozymes among the populations depicted by pairwise
      F(ST)/G(ST), AMOVA, Nei's genetic distance, and UPGMA dendrogram. The three
      classes of markers demonstrated striking genetic differentiation between pairs of
      H. brachysoma populations. The data emphasize the need for fishery management,
      conservation, and rehabilitation of this species.

PMID- 21938563
TI  - The impact of bilingual environments on language development in children with
      autism spectrum disorders.
AB  - The impact of bilingual exposure on language learning has not been systematically
      studied in children with Autism Spectrum Disorders. This study compared the
      social abilities and language levels of children (mean age = 56 months) with ASDs
      from bilingual (n = 45) and monolingual (n = 30) environments. Bilingually
      exposed children were subgrouped based on simultaneous bilingual exposure from
      infancy (SIM, n = 24) versus sequential post-infancy bilingual exposure (SEQ, n =
      21). Despite significantly different amounts of bilingual exposure across all
      groups (p = <0.001) and significantly stronger social interaction scores in the
      SIM group compared to the SEQ group on the Vineland Adaptive Behavior Scales-II
      Interpersonal subdomain (p = 0.025), there were no significant group differences
      in language level. Bilingually-exposed children with ASDs did not experience
      additional delays in language development.

PMID- 21938564
TI  - Everolimus-eluting stents for treatment of chronic total coronary occlusions.
AB  - BACKGROUND: After successful recanalization of a coronary chronic total occlusion
      (CTO) the risk for restenosis and subsequent need for repeat intervention is
      high. Everolimus-eluting stents (EESs) were associated with low rates of
      restenosis, reintervention and stent thrombosis in non-occluded lesions. We
      sought to determine the antiproliferative impact of the everolimus-eluting Xience
      V stent in CTOs. METHODS: Fifty-three patients with a CTO in a native coronary
      artery were included. CTO was defined as a duration of occlusion >=3 months and
      thrombolysis in myocardial infarction 0 flow. EESs were exclusively implanted to
      completely cover the occluded and adjacent stenotic segments. Dual antiplatelet
      therapy was prescribed for 6 months. Follow-up angiography was scheduled at 6
      months. Clinical follow-up was done at 12 months. The primary endpoint was late
      loss at the initial occlusion site. Secondary clinical endpoint was a composite
      of cardiac death, myocardial infarction not clearly attributable to a non-target
      vessel and target lesion revascularization. RESULTS: Mean occlusion length was 24
      +/- 17 mm, ranging from 4 to 74 mm. Mean stent length was 79 +/- 36 mm, ranging
      from 18 to 158 mm. Reference diameter was 3.27 +/- 0.58 mm. Late loss at the
      initial occlusion site was 0.22 +/- 0.69 mm. There were six (11%) binary
      restenosis with a target lesion reintervention in three (6%) patients. There was
      no death, myocardial infarction or stent thrombosis within 12 months. CONCLUSION:
      In patients with successful recanalization of complex CTOs the use of EESs
      results in a low angiographic late loss and restenosis rate without stent
      thrombosis throughout 12 months follow-up.

PMID- 21938565
TI  - [Bladder cancer at an early age in father and son].
AB  - Bladder cancer may be caused by external factors like tobacco smoking, but may
      also be familial. We report on a father and son who developed this tumour at the
      ages of 45 and 35. Testing various genetic markers including the mismatch repair
      proteins MLH1, MSH2 and MSH6, whose loss is associated with a higher risk for
      hereditary non-polyposis colorectal cancer (HNPCC, Lynch syndrome), did not point
      to a familial disease. Thus the heavy smoking habits of the two patients must be
      considered as causal.

PMID- 21938566
TI  - Epigenetic CpG demethylation of the promoter and reactivation of the expression
      of Neurog1 by curcumin in prostate LNCaP cells.
AB  - Curcumin (CUR), a major bioactive polyphenolic component from turmeric curry,
      Curcuma longa, has been shown to be a potent anti-cancer phytochemical with well
      established anti-inflammatory and anti-oxidative stress effects. Chromatin
      remodeling-related epigenetic regulation has emerged as an important mechanism of
      carcinogenesis, chemoprevention, and chemotherapy. CUR has been found to inhibit
      histone acetyltransferase activity, and it was also postulated to be a potential
      DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitor. In this
      study, we show that when human prostate LNCaP cells were treated with CUR, it led
      to demethylation of the first 14 CpG sites of the CpG island of the Neurog1 gene
      and restored the expression of this cancer-related CpG-methylation epigenome
      marker gene. At the protein level, CUR treatment had limited effects on the
      expression of epigenetic modifying proteins MBD2, MeCP2, DNMT1, and DNMT3a. Using
      ChIP assay, CUR decreased MeCP2 binding to the promoter of Neurog1 dramatically.
      CUR treatment showed different effects on the protein expression of HDACs,
      increasing the expression of HDAC1, 4, 5, and 8 but decreasing HDAC3. However,
      the total HDAC activity was decreased upon CUR treatment. Further analysis of the
      tri-methylation of histone 3 at lysine 27 (H3K27me3) showed that CUR decreased
      the enrichment of H3K27me3 at the Neurog1 promoter region as well as at the
      global level. Taken together, our present study provides evidence on the CpG
      demethylation ability of CUR on Neurog1 while activating its expression,
      suggesting a potential epigenetic modifying role for this phytochemical compound
      in human prostate cancer cells.

PMID- 21938567
TI  - Timing of laparoscopic surgery in the neoadjuvant treatment of rectal cancer.

PMID- 21938568
TI  - A pilot study of the technical and oncologic feasibility of thoracoscopic
      esophagectomy with extended lymph node dissection in the prone position for
      clinical stage I thoracic esophageal carcinoma.
AB  - BACKGROUND: Thoracoscopic esophagectomy in the prone position (TSEP) without
      thoracotomy is more invasive than right transthoracic esophagectomy (TTE).
      However, TTE and TSEP have not been compared in terms of technical and
      oncological feasibility for thoracic esophageal carcinomas of the same stage.
      METHODS: Fifty-nine patients with clinical stage I esophageal cancer underwent
      esophagectomy with three-field lymph node dissection from 2000 through 2010, 30
      patients underwent right TTE through 2008, and 29 patients underwent TSEP from
      2008 through 2010. TSEP was performed with four ports from 2008 through 2009 (13
      patients) and with five ports--four conventional ports and a 5 mm camera port for
      the upper mediastinum--from 2009 (16 patients). We retrospectively evaluated the
      technical and oncologic feasibility of TSEP with extended lymph node dissection
      for clinical stage I thoracic esophageal carcinoma by comparing surgical outcomes
      between TTE and TSEP and examined the historical improvements and current status
      of TSEP, including port placement. RESULTS: All 29 patients who underwent TSEP
      with three-field lymph node dissection achieved complete resection, and in the 13
      patients followed up for more than 1 year, there were no surgery-related
      postoperative deaths and no recurrence. No significant difference was found
      between TTE and TSEP in the mean number of dissected mediastinal lymph nodes,
      amount of blood loss, incidence of postoperative complications, mean
      postoperative hospital stay, or rate of complete resection or locoregional
      control, but the mean duration of thoracic procedure was significantly longer for
      TSEP than for TTE. For TSEP, the incidence of complications was lower and the
      postoperative hospital stay was shorter with five ports than with four ports.
      CONCLUSIONS: TSEP with extended lymphadenectomy is a feasible and appropriate
      surgical technique for clinical stage I thoracic esophageal carcinoma. We believe
      that its oncological feasibility for advanced esophageal carcinoma also will be
      demonstrated.

PMID- 21938569
TI  - SAGES' guidelines for diagnosis, treatment, and use of laparoscopy for surgical
      problems during pregnancy.

PMID- 21938571
TI  - Laparoscopic subtotal colectomy with transrectal extraction of the colon and
      ileorectal anastomosis.
AB  - BACKGROUND: Despite the growing acceptance of laparoscopic colon surgery, an
      abdominal incision is needed to remove the specimen and perform an anastomosis.
      METHODS: Five trocars (one 12 mm and four 5 mm) were used. The video describes
      the technique of performing laparoscopic subtotal colectomy, laparoscopic
      cholecystectomy, transrectal removal of the gallbladder and the entire colon, and
      intracorporeal stapled ileorectal anastomosis in a 27-year-old female with
      colonic inertia and biliary dyskinesia. RESULTS: There were no intraoperative
      complications. The operating time was 180 min. Blood loss was 10 cc. The patient
      was discharged home on postoperative day 4. CONCLUSION: Laparoscopic subtotal
      colectomy with transrectal removal of the colon is a safe and effective procedure
      that can be added to the armamentarium of surgeons performing laparoscopic colon
      surgery. This technique may provide both an attractive way to reduce abdominal
      wall morbidity and a bridge to NOTES colon surgery.

PMID- 21938570
TI  - Guidelines for diagnosis, treatment, and use of laparoscopy for surgical problems
      during pregnancy.

PMID- 21938572
TI  - Smoke evacuation in single-incision laparoscopic surgery.

PMID- 21938573
TI  - "Correcting" ulcers?

PMID- 21938574
TI  - Evaluation of complications related to therapeutic colonoscopy using the bipolar
      snare.
AB  - BACKGROUND: The complications with therapeutic colonoscopy reported to date have
      been associated with the monopolar snare, and the frequency of complications
      related to use of the bipolar snare is uncertain. This study aimed too
      investigate the incidence of bleeding and perforation associated with the bipolar
      snare and to identify the risk factors for bleeding. METHODS: Between October
      2001 and December 2008, all patients with colorectal polyps treated using the
      bipolar snare were enrolled in this retrospective study. Clinical data were
      assembled from an electronic database. The incidence of bleeding and perforation
      was investigated, and the risk factors for bleeding also were determined using
      multivariate analysis. RESULTS: This study collected 4,719 patients with 10,513
      lesions. Perforation occurred for eight patients (0.17%) and bleeding in 66
      patients (1.4%). Age younger than 60 years was a significant risk factor for
      bleeding (P < 0.01). The incidence of bleeding was significantly higher for
      lesions 10 mm or larger than for lesions smaller than 10 mm (P < 0.001). In terms
      of macroscopic type, pedunculated lesions bled significantly more often than
      lesions of other shapes (P < 0.001). Lesions in the rectum bled significantly
      more frequently (P < 0.001) than lesions at other sites. High-grade dysplasia and
      invasive cancer developed bleeding significantly more often than other histologic
      types (P < 0.001). Multivariate analysis showed that age younger than 60 years
      (odds ratio [OR], 2.42), lesion size of 10 mm or larger (OR, 2.60), pedunculated
      shape (OR, 3.40), and rectal location (OR, 3.55) were significant risk factors.
      CONCLUSIONS: The complication rates for the bipolar snare appear to be comparable
      with those for the monopolar snare based on comparison of the results reported in
      the literature. Age (<60 years), lesion size (>= 10 mm), macroscopic type
      (pedunculated), and lesion location (rectum) are independent risk factors for
      bleeding.

PMID- 21938575
TI  - Evaluation of a simple valve mechanism used to stabilize intraabdominal pressure
      during surgically induced pneumoperitoneum in small animals.
AB  - BACKGROUND: Preventing sudden changes in intraabdominal pressure (IAP) during
      surgical pneumoperitoneum may reduce adverse events. This study aimed to describe
      a valve system that stabilizes intraabdominal pressure, minimizing complications
      of erratic fluctuations in IAP. METHODS: Five male Sprague-Dowley rats were
      submitted to pneumoperitoneum, with the insufflator set sequentially at 5, 10,
      and 15 mmHg for each rat. Measures of IAP were taken initially without the valve
      and then using the same insufflator levels with the valve system regulated to
      three different pressures (5, 10, and 15 mmHg). The mean of the three highest
      registered pressures during a 15-min observation was used as the maximal
      pressure, and the mean of the three lowest registered pressures was used as the
      minimal pressure for each experimental setting. RESULTS: Without the valve
      system, the pressure level set by the insufflator correlated poorly with the
      actual IAP. When the valve system was used, the IAP pressure was limited by the
      valve settings regardless of the insufflator settings. Also, the variability of
      IAP was significantly higher when no valve was used than in all situations that
      had implementation of the system. CONCLUSIONS: The valve system was very
      effective in stabilizing IAP, allowing a reproducible and reliable estimate of
      IAP and greatly reducing the variability resulting from the cycling mechanism of
      the insufflator. Due to the small dimensions of intracorporeal cavities in the
      newborn, this mechanism may help to improve safety when neonatal video-assisted
      surgery is performed.

PMID- 21938576
TI  - Transumbilical laparoscopically assisted appendectomy in children: the results of
      a single-port, single-channel procedure.
AB  - BACKGROUND: Even for pediatric patients, the use of laparoscopic appendectomy has
      been widely accepted, and three trocars usually are necessary to perform a
      laparoscopic appendectomy. However, single-port appendectomy for children
      represents an attractive alternative. To reduce the number of incisions and
      trocars, the authors have adopted a transumbilical laparoscopically assisted
      single-port appendectomy (TULAA) approach. This study aimed to evaluate the
      results of their single-channel, single-port appendectomy. METHODS: A
      retrospective study of TULAA was performed during 12 years with 500 children ages
      2-16 years (median, 10.2 years). The TULAA approach is a single-channel surgery
      using a 12 mm conventional single-port. The vertical incision through the
      umbilicus is used for laparoscopic access. Two laparoscopic instruments, a 5 mm
      telescope and a 5 mm grasper, are inserted simultaneously into the single
      channel. The grasper holds the base of the appendix, and the appendix is
      exteriorized through the umbilical incision. Thereafter, a conventional
      appendectomy is performed extracorporeally. RESULTS: The TULAA procedure was
      successful for 416 patients (83.2%). These successful TULAA procedures required a
      mean surgery time of 44.5 min. The pathologic diagnosis of the appendix was acute
      for 59 patients, phlegmonous for 203 patients, gangrenous for 152 patients, and
      not detected for two patients. Complications occurred for 47 of these patients
      (11.3%). Most of the complications were associated with severe intraabdominal
      inflammation. Two patients needed reoperation under general anesthesia.
      Conversion to multitrocar surgery or open appendectomy was performed for 84 of
      the patients (16.8%). CONCLUSIONS: The TULAA procedure is a preferable operation
      for acute appendicitis in children because it is simple and provides good
      cosmetic results.

PMID- 21938577
TI  - The role of endoscopic ultrasound in assessing tumor response and staging after
      neoadjuvant chemotherapy for esophageal cancer.
AB  - BACKGROUND: Although the role of endoscopic ultrasound (EUS) in the initial
      staging of esophageal cancer is well established, its role in assessing tumor
      response and staging esophageal cancers after neoadjuvant chemotherapy (NAC) is
      controversial, and this study aimed to investigate this role. METHODS: This study
      retrospectively analyzed 110 patients with esophageal cancer who underwent EUS by
      single surgeon before and after NAC. Tumor response was assessed before and after
      NAC. Patients with more than a 50% reduction in tumor size based on EUS
      evaluation were classified as having a significant response to chemotherapy, and
      those with less than a 50% reduction were categorized as having a partial
      response. Disease stage was established by tumor node metastasis (TNM)
      classification. Initial staging was performed using EUS and computed tomography
      (CT) scans of the chest and abdomen. The EUS-determined stage was compared with
      the postsurgical pathologic stage. chi(2) analysis and Fisher's exact testing
      were performed. RESULTS: A response to NAC was shown by 96 patients (87.3%) and
      no response by 14 patients (12.7%). Of the 96 responding patients, 37 (38.5%)
      showed a significant response, whereas 43 (61.5%) of 69 patients showed a partial
      response. The EUS staging correlated well with the pathologic staging for 9
      (64.3%) of the 14 nonresponders and for 34 (35.4%) of the 96 responders to NAC (P
      = 0.04). The EUS accurately predicted both the T and N status for 26 (23.6%) of
      the 110 patients. Prediction of N status was significantly more accurate than
      prediction of the T stage for the post-NAC patients. Of the 110 patients, 43
      (39.1%) patients had an accurate T-stage prediction, and 64 (58.2%) had an
      accurate N stage match (P = 0.02). The T stage was overstaged for 60 (54.5%) of
      the patients and understaged for 7 of the patients (6.4%).The study found
      overstaging of the T stage to be more common among the patients who responded to
      chemotherapy. The N stage was overstaged for 25 (22.7%) and understaged for 21
      (19.1%) of the 110 patients. CONCLUSION: The findings showed EUS to be a useful
      tool for assessing response to chemotherapy and for evaluating the extent of
      disease, thus facilitating surgical decision making. However, EUS is an
      unreliable tool for staging esophageal cancer after NAC. Overstaging of the T
      stage is significantly more common and could be related to the inflammatory
      effect or fibrosis after NAC.

PMID- 21938578
TI  - Does adding a lesser-curvature gastrogastric plication suture reduce the need for
      revision after laparoscopic adjustable gastric band placement?
AB  - BACKGROUND: The need for revision after laparoscopic adjustable gastric band
      (LAGB) surgery has been reduced over the past 10 years with the introduction of
      the pars flaccida technique, delicate band tightening, and concurrent hiatal
      hernia repairs. However, band revision still occurs for as many as 5% of
      patients. Placement of a lesser-curvature gastrogastric suture distal to the band
      is one newer technique suggested to lower band slippage. To evaluate the worth of
      this technique, the authors have investigated two groups of patients in their
      practice: one group with the plication stitch and one group without it. METHODS:
      This retrospective review examined data for 1,365 LAGB patients collected
      prospectively by an institutional review board-approved database between July
      2007 and May 2010. One surgeon did not perform the plication stitch (n = 776) and
      one did (n = 589). The surgical techniques were very similar. The majority of the
      patients had crural repair at the primary operation. Band revision rates were
      assessed. RESULTS: For 1,365 patients, LAGB was performed safely. The mean follow
      up period was 22 months. The two groups were similar. The no-stitch group
      consisted of 776 patients (496 women, 64%) with a mean age of 42 years, a mean
      weight of 278 lb, and a mean body mass index (BMI) of 44.6 kg/m(2). The stitch
      group consisted of 589 patients (426 woman, 72%) with a mean age of 40 years, a
      mean weight of 278 lb, and a mean BMI of 44.8 kg/m(2). The no-stitch group had an
      estimated weight loss (EWL) of 44% at 12 months and 50% EWL at 2 years. The
      stitch group had 37% EWL at 12 months and 45% EWL at 2 years. Both groups had
      very low revision rates. The no-stitch group had 4 revisions in 776 patients
      (0.26%), and the stitch group had 9 revisions in 589 patients (1.5%). CONCLUSION:
      Adding gastrogastric plication sutures offers no benefit of reducing the rate of
      revision after LAGB surgery.

PMID- 21938579
TI  - Laparoscopic cholecystectomy after a quarter century: why do we still convert?
AB  - BACKGROUND: Laparoscopic cholecystectomy (LC) is the gold standard procedure for
      gallbladder removal. However, conversion to open surgery is sometimes needed. The
      factors underlying a surgeon's decision to convert a laparoscopic case to an open
      case are complex and poorly understood. With decreasing experience in open
      cholecystectomy, this procedure is however no longer the "safe" alternative it
      once was. With such an impending paradigm shift, this study aimed to identify the
      main reasons for conversion and ultimately to develop guidelines to help reduce
      the conversion rates. METHODS: Using the National Surgical Quality Improvement
      Program (NSQIP) database and financial records, the authors retrospectively
      reviewed 1,193 cholecystectomies performed at their institution from 2002 to 2009
      and identified 70 conversions. Two independent surgeons reviewed the operative
      notes and determined the reasons for conversion. The number of ports at the time
      and the extent of dissection before conversion were assessed and used to create
      new conversion categories. Hospital length of stay (LOS), 30-day complications,
      operative times and charges, and hospital charges were compared between the new
      groups. RESULTS: In 91% of conversion cases, the conversion was elective. In 49%
      of these conversions, the number of ports was fewer than four. According to the
      new conversion categories, most conversions were performed after minimal or no
      attempt at dissection. There were no differences in LOS, complications, operating
      room charges, or hospital charges between categories. Of the six emergent
      conversions (9%), bleeding and concern about common bile duct (CBD) injury were
      the main reasons. One CBD injury occurred. CONCLUSIONS: In 49% of the cases,
      conversion was performed without a genuine attempt at laparoscopic dissection.
      Considering this new insight into the circumstances of conversion, the authors
      recommend that surgeons make a genuine effort at a laparoscopic approach, as
      reflected by placing four ports and trying to elevate the gallbladder before
      converting a case to an open approach.

PMID- 21938580
TI  - Capnographic monitoring for carbon dioxide insufflation during endoscopic
      submucosal dissection: comparison of transcutaneous and end-tidal capnometers
      [corrected].
AB  - BACKGROUND: The use of carbon dioxide (CO(2)) insufflation during endoscopic
      procedures is effective in reducing patient discomfort caused by bloating.
      However, transcutaneous arterial CO(2) (PtCO(2)) monitoring usually is required
      for safety during long endoscopic procedures. To evaluate a new capnometer for
      monitoring end-tidal carbon dioxide (EtCO(2)) concentrations and to compare
      PtCO(2) with EtCO(2) measured in the same patient, a prospective comparative
      study of EtCO(2) and PtCO(2) values measured simultaneously was designed.
      METHODS: The study enrolled 20 consecutive patients (18 men and two women; mean
      age, 70.1 years) with upper gastrointestinal neoplasms scheduled for endoscopic
      submucosal dissection (ESD) using conscious sedation with CO(2) insufflation, and
      EtCO(2) and PtCO(2) were simultaneously measured by each capnometer. Patient
      status was evaluated before ESD by the American Society of Anesthesiologists
      (ASA) physical status classification system, and eight patients were judged as
      class 1, nine patients as class 2, and three patients as class 3. The exclusion
      criteria ruled out patients with chronic obstructive pulmonary disease or ASA
      class 4 or 5 physical status. The correlation between EtCO(2) and PtCO(2) values
      and the availability of EtCO(2) capnography were investigated. RESULTS: The mean
      EtCO(2) value during ESD was 34.7 +/- 4.5 mmHg, and the mean PtCO(2) value was
      51.6 +/- 2.4 mmHg. There was a statistically significant correlation between
      EtCO(2) and PtCO(2) (r = 0.331; P = 0.002). Hypoxic events (<90% oxygen
      saturation [SpO(2)]) caused by decreased respiratory rate occurred for 12
      patients. In 10 (83%) of 12 events, a significant reduction in EtCO(2) was seen
      before the decrease in SpO(2). CONCLUSIONS: The EtCO(2) values correlated with
      the PtCO(2) values, and the respiratory monitoring methods allowed earlier
      detection of hypoxia during ESD with conscious sedation than transcutaneous
      monitoring. The EtCO(2) capnometer was considered to be available for the ESD
      procedure with the patient under conscious sedation using CO(2) insufflation.

PMID- 21938581
TI  - Learning laparoscopic colectomy during colorectal residency: what does it take
      and how are we doing?
AB  - BACKGROUND: The ability to perform a laparoscopic colectomy is an integral part
      of a young colorectal surgeon's practice. However, the number of resections
      required during colorectal residency for a surgeon to be very comfortable
      performing a laparoscopic colectomy independently is poorly defined. Furthermore,
      the percentage of trainees that achieve this goal also is unknown. METHODS: An
      electronic survey designed by the Young Surgeon's Committee of the American
      Society of Colon and Rectal Surgeons (ASCRS) was sent to graduates completing
      Accreditation Council for Graduate Medical Education (ACGME) colorectal
      residencies after publication of the Clinical Outcomes Study Group (COST) trial
      (2004-2009). The data collected included the number of laparoscopic right (LR),
      laparoscopic left (LL), and laparoscopic hand-assisted left (HAL) colectomies
      performed during residency. Trainees were asked to assess whether at the
      completion of their fellowship they with each case were very comfortable (VC,
      would perform a laparoscopic colectomy independently), somewhat comfortable (SC,
      would require assistance from colleagues), or not comfortable (NC, would not
      perform a laparoscopic colectomy). RESULTS: Of the 176 (51%) former fellows
      responding to the survey, 42 (24%) reported performing fewer than 10 LRs, 108
      (62%) reported 10 to 30 LRs, and 24 (14%) reported more than 30 LRs during their
      fellowship. With LR, 13 (7.5%) respondents were NC, 42 (21%) were SC, and 119
      (68%) were VC. As reported, 58 fellows (33%) performed fewer than 10 LLs, 92
      (53%) performed 10-30 LLs, and 22 (13%) performed more than 30 LLs. With LL,
      12.2% were NC, 33.7% were SC, and 54.1% were VC. Most of the fellows (90%) who
      performed 30 or more LR, LL, or HAL colectomies were VC. On the average, each
      year's graduating fellows were more comfortable with laparoscopic colectomy than
      those graduating in previous years (P < 0.002). CONCLUSIONS: Performing more than
      10 LR colectomies and more than 30 LL colectomies provided the vast majority of
      colorectal residents with the ability to be very comfortable with these
      procedures as they entered practice. A concerning number of trainees (46% of LL
      and 24% of LR trainees) did not reach this benchmark. The new general minimal
      American Board of Colon and Rectal Surgery (ABCRS) requirement of 50 laparoscopic
      resections seems appropriate but may require definition regarding the side of the
      procedure.

PMID- 21938582
TI  - Initial experience with laparoscopic hepatic resection at a comprehensive cancer
      center.
AB  - BACKGROUND: Over the past few years, surgeons have been able to obtain training
      in advanced minimally invasive surgery (MIS) for hepatic, pancreatic, and biliary
      (HPB) cases instead of having to teach themselves these complex techniques. As a
      result, the initial experience of a surgeon with advanced MIS HPB training at a
      national cancer center was reviewed. METHODS: The experience of a surgeon with
      the first 50 laparoscopic hepatectomies for cancer was reviewed retrospectively.
      All cases begun with the intention to complete the hepatectomy laparoscopically
      were included in the laparoscopic group. RESULTS: From November 2008 to October
      2010, a total of 57 hepatectomies were performed, with 53 attempted
      laparoscopically. Of these 57 hepatectomies, 46 (87%) were completed
      laparoscopically, 4 (7%) required hand assistance, and 3 (6%) were converted to
      an open approach. Laparoscopic minor hepatectomies were performed for 28 patients
      and laparoscopic major hepatectomies for 25 patients. The mean operative time was
      265 min, and the mean estimated blood loss was 300 ml. The mean hospital stay was
      7 days. Complications occurred for six patients (11%) (2 bile leaks, 2
      hemorrhages requiring conversion, 1 hernia requiring a hernia repair on
      postoperative day 7, and 1 ileus managed nonoperatively). CONCLUSIONS: Surgeons
      with advanced MIS HPB training may be able to perform a higher percentage of
      their hepatectomies laparoscopically. Training in both open and laparoscopic HPB
      surgery is advisable before these techniques are performed.

PMID- 21938583
TI  - Therapeutic options for iatrogenic colon perforation: feasibility of endoscopic
      clip closure and predictors of the need for early surgery.
AB  - BACKGROUND: The therapeutic methods of iatrogenic colon perforation have not been
      performed despite the increasing rates of successful management by endoscopic
      clip closure. This study aimed to analyze the efficacy and complications of
      endoscopic clip closure and to identify the risk factors associated with the need
      for early surgery to avoid more invasive surgical interventions and adverse
      complications after endoscopic clip closure for iatrogenic colon perforation.
      METHODS: A retrospective multicenter review of the clinical course experienced by
      32 patients with iatrogenic colon perforation who were treated using immediate
      endoscopic clip closure between January 2005 and December 2009 was performed.
      RESULTS: The technical success rate for endoscopic clip closure was 91% (29/32).
      After endoscopic clip closure, 22 patients (76%) required medical treatment for
      colon perforation, and seven patients (24%) had surgical treatment. Of the 22
      patients who had only endoscopic clip closure, 17 (59%) had a favorable clinical
      course. Five patients had a long hospital stay with complication including
      abscess formation (three cases). Four patients underwent early surgery within 24
      h, and laparoscopic simple closure was possible. But for three patients with
      surgery delayed more than 48 h, open laparotomy with colon resection including
      diversion were required. The risk factors associated with the need for early
      surgical treatment within 24 h after endoscopic clip closure were a large
      perforation [odds ratio (OR), 9.25; 95% confidence interval (CI), 1.85-46.20],
      leukocytosis (OR 6.58; 95% CI 1.86-23.29), fever (OR 5.05; 95% CI 1.05-24.28),
      severe abdominal pain (OR 4.30; 95% CI 1.17-15.83), and a large amount of
      peritoneal free air (OR 4.05; 95% CI 1.40-11.71). CONCLUSION: The endoscopic clip
      closure procedure can significantly reduce the frequency of surgery among
      patients with iatrogenic colon perforations. However, the decision for surgery
      must be made early after endoscopic clip closure to prevent adverse complications
      for patients with higher risk factors.

PMID- 21938585
TI  - Reply to: doi:10.1007/s00464-010-1243-3: Surgery in space: the future of
      telerobotic surgery.

PMID- 21938584
TI  - Laparoscopic resection of a residual retroperitoneal tumor mass of
      nonseminomatous testicular germ cell tumors.
AB  - BACKGROUND: Resection of a residual retroperitoneal tumor mass (RRRTM) is
      standard procedure after combination chemotherapy for metastatic nonseminomatous
      testicular germ cell tumors (NSTGCT). METHODS: At the University Medical Center
      Groningen, 79 consecutive patients with disseminated NSTGCT were treated with
      cisplatin combination chemotherapy between 2005 and 2007. Laparoscopic RRRTM was
      performed for patients with RRTM located less than 5 cm ventrally or laterally
      from the aorta or the vena cava. The 29 patients who fulfilled the criteria had a
      median age of 25 years (range, 16-59 years). The stages of disease before
      chemotherapy treatment according to the Royal Marsden classification were 2A (n =
      6, 21%), 2B (n = 14, 48%), 2C (n = 3, 10%), and 4 with a lymph node status of N2
      (n = 6, 21%). RESULTS: The median duration of laparoscopy was 198 min (range, 122
      325 min). The median diameter of the RRTM was 21 mm (range, 11-47 mm).
      Laparoscopic resection was successful for 25 patients (86%). Conversion was
      necessary for three patients (10%): two due to bleeding and one because of
      obesity. One nonplanned hand-assisted procedure (3%) also had to be performed.
      Histologic examination of the specimens showed fibrosis or necrosis in 12
      patients (41%), mature teratoma in 16 patients (55%), and viable tumor in 1
      patient (3%). The median hospital stay was 1 day (range, 1-6 days). During a
      median follow-up period of 47 months (29-70 months), one patient experienced an
      early relapse (1 month after the end of treatment) (4%). CONCLUSION: For properly
      selected patients, laparoscopic resection of RRTM is an improvement in the
      combined treatment of disseminated NSTGCT and associated with a short hospital
      stay, minimal morbidity, rapid recovery, and a neat cosmetic result. Long-term
      data to prove oncologic efficacy are awaited.

PMID- 21938586
TI  - Multivisceral resections in pancreatic cancer: identification of risk factors.
AB  - BACKGROUND: There is an assumption that multivisceral resections (MVRs) in
      patients with a pancreatic malignancy are associated with higher morbidity. The
      oncologic benefit, however, remains controversial. METHODS: The aim was to
      identify risk factors for complications in cases of MVR in patients with
      pancreatic cancer. Of 1099 patients who underwent major pancreatic resection at
      our institution between January 1992 and October 2008, a total of 55 were treated
      with an MVR involving resection of one or more additional organs. This group was
      compared with 154 patients who had palliative bypass surgery and 303 patients who
      underwent standard pancreatic head resection. RESULTS: Multivisceral resection
      patients had an overall higher incidence of major surgical complications (p <
      0.001). In-hospital mortality was comparable in all groups. Median survival after
      MVR was inferior to that after standard resection but was significantly better
      than that after palliative bypass. Univariate logistic regression analysis
      identified concomitant colon, kidney, and liver resections and any intraoperative
      transfusion as predictors of complications; in the multivariate analysis, only
      kidney resections and any intraoperative transfusion were confirmed predictors.
      In contrast, T status, kidney resection, resection of four or more organs, any
      postoperative transfusion, and intensive care unit stay of >2 days were
      identified as predictors of survival in the univariate Cox regression analysis;
      in the multivariate analysis, only the T status was confirmed. Median survival
      after MVR was 16 months, after palliative bypass 6 months, and after standard
      resection 18 months (p < 0.001). CONCLUSIONS: Multivisceral resections are
      technically feasible procedures with increased survival when compared to
      palliative bypass procedures. The incidence of postoperative complications was
      increased with kidney resection and when intraoperative transfusion was required.

PMID- 21938587
TI  - Collagen scaffolds with or without the addition of RGD peptides support
      cardiomyogenesis after aggregation of mouse embryonic stem cells.
AB  - Embryonic stem (ES) cell-based cardiac muscle repair using tissue-engineered
      scaffolds is an attractive prospective treatment option for patients suffering
      from heart disease. In this study, our aim was to characterize mouse ES cell
      derived cardiomyocytes growing on collagen I/III scaffolds, modified with the
      adhesion peptides arginine-glycine-aspartic acid (RGD). Mouse ES-derived embryoid
      bodies (EBs) differentiated efficiently into beating cardiomyocytes on the
      collagen scaffolds. QPCR analysis and immunofluorescent staining showed that
      cardiomyocytes expressed cardiac muscle-related transcripts and proteins.
      Analysis of cardiomyocytes by electron microscopy identified muscle fiber bundles
      and Z bands, typical of ES-derived cardiomyocytes. No differences were detected
      between the collagen + RGD and collagen control scaffolds. ES cells that were not
      differentiated as EBs prior to seeding on the scaffold, did not differentiate
      into cardiomyocytes. These results indicate that a collagen I/III scaffold
      supports cardiac muscle development and function after EB formation, and that
      this scaffold appears suitable for future in vivo testing. The addition of the
      RGD domain to the collagen scaffold did not improve cardiomyocyte development or
      viability, indicating that RGD signaling to integrins was not a rate-limiting
      event for cardiomyogenesis from EBs seeded on a collagen scaffold.

PMID- 21938588
TI  - Adipogenic differentiation of chicken epithelial oviduct cells using only chicken
      serum.
AB  - Chicken epithelial oviduct cells (COCs) are part of important supportive tissues
      in chicken reproductive organs responsible for secretion of the majority of
      chicken egg protein. In chickens, the biological process of adipocyte
      differentiation has been extensively studied in vitro using a number of cell
      types including a preadipocyte precursor cell line, a number of other
      undifferentiated cell lines, and chicken embryonic fibroblasts. On the contrary,
      adipogenic differentiation in epithelial cells has not yet been achieved. In our
      study, we induced COCs to differentiate into adipocytes using chicken serum at
      concentrations of 5% and 10%. After a 24-h culture period at 37 degrees C in a
      humidified 5% CO(2) atmosphere, oviduct cell morphology changed dramatically
      through formation of lipid droplets, observed by Oil Red O staining. Also,
      chicken serum strongly induced 3T3-L1 preadipocyte cell differentiation into
      adipocyte. In addition, mRNA expression levels of peroxisome proliferator
      activated receptor gamma, adipocyte fatty acid-binding protein (aP2), and CCAAT
      enhancer-binding protein alpha were significantly increased 48 h after induction.
      These results suggest that COCs can be induced to differentiate into adipocyte
      like cells. Moreover, through this study, we confirmed that chicken serum is an
      effective adipocyte differentiation-inducing agent. Our findings may provide a
      unique model for studying and applying chicken transdifferentiation and adipocyte
      differentiation.

PMID- 21938589
TI  - Human amniotic fluid-derived stem cells can differentiate into hepatocyte-like
      cells in vitro and in vivo.
AB  - Although human amniotic fluid is an attractive source of multipotent stem cells,
      the potential of amniotic fluid stem cells (AFSCs) to differentiate into hepatic
      cells has not been extensively evaluated. In this study, we examined whether
      human AFSCs can differentiate into a hepatic cell lineage in vitro and in vivo.
      After being treated with cytokines (fibroblast growth factor 4, basic fibroblast
      growth factor, hepatocyte growth factor, and oncostatin), AFSCs developed a
      morphology similar to that of hepatocytes. RT-PCR and immunofluorescence analysis
      showed that the treated AFSCs expressed the hepatocyte-specific markers albumin,
      cytokeratin 18, and alpha-fetoprotein. The differentiated cells also developed
      hepatocyte-specific functions, i.e., they secreted albumin, absorbed indocyanine
      green, and stored glycogen. When transplanted into CCl(4)-injured immunodeficient
      mice, undifferentiated AFSCs were integrated into the liver tissue, and they
      expressed markers characteristic of mature human hepatocytes. Although
      integration of AFSCs into the liver was limited (0.1-0.3% of hepatocytes),
      histological analysis showed that the recipient mice recovered more rapidly from
      CCl(4) injury than CCl(4)-injured mice that did not receive AFSCs. AFSCs can
      differentiate into hepatocyte-like cells in vitro and in vivo and can represent
      an easily accessible source of progenitor cells for hepatocyte regeneration and
      liver cell transplantation.

PMID- 21938590
TI  - Misidentification of OLGA-PH-J/92, believed to be the only crustacean cell line.
AB  - Continuous cell lines from aquatic invertebrate species are few and the
      development of crustacean cell lines remains an elusive goal. Although a crayfish
      cell line derived from neural ganglia of Orconectes limosus was reported in 2000,
      this cell line OLGA-PH-J/92 failed to be authenticated as such. In this report,
      we describe our attempts to identify the taxonomic identity of the cell line
      through immunological and molecular techniques. Immunohistochemical screening for
      the expression of a suite of invertebrate neuropeptides gave negative results,
      precluding an invertebrate neural origin. PCR amplification and DNA sequencing
      for the mitochondrial cytochrome c oxydase I, and 18S ribosomal RNA genes that
      had been widely used to confirm species identity, could not confirm the OLGA-PH
      J/92 cells as originating from crayfish. Subsequent attempts to identify the
      cells provided moderate homology (82%) to Gephyramoeba sp. (AF293897) following
      PCR amplification of an 18S rDNA fragment after a BLAST search. A literature
      search provided morphological evidence of the similarity of OLGA-PH-J/92 to the
      Gephyramoeba distributed by the American Type Culture Collection as ATCC 50654,
      which also had been misidentified and was renamed Acramoeba dendroida (Smirnov et
      al., Eur J Protistol 44:35-44, 2008). The morphology of the OLGA-PH-J/92 cells
      which remains identical to the original report (Neumann et al., In Vivo 14:691
      698, 2000) and matched corresponding micrographs that were available from the
      ATCC before the cell line was dropped from their catalog (ATCC CRL 1494) is very
      similar to A. dendroida and could thus belong to the Acramoebidae. These results
      unequivocally indicate that the OLGA-PH-J/92 cell line is not derived from the
      crayfish O. limosus, and the search for an immortal crustacean cell line
      continues.

PMID- 21938592
TI  - Reverse nasal SMAS-perichondrium flap to avoid supratip deformity in rhinoplasty.
AB  - BACKGROUND: Supratip deformity is an iatrogenic convexity that occurs
      cephalically to the nasal tip. This is also known as "parrot beak" deformity and
      causes an unnatural appearance of the nose. In the literature there are several
      explanations of the mechanism of the deformity and methods to correct it. One of
      the most accepted theories about the cause of supratip deformity is overresection
      of the caudal dorsum. Healing soft tissues fill in the gap created between the
      septum and the tip of the lower lateral cartilages, leading to fullness in the
      supratip area. The lower third and basically distal third of the middle third of
      the nose include several muscle groups, ligamentous structures, and perichondrium
      as the subcutaneous soft tissues. METHODS: With the idea of elevating a reverse
      based flap basically from the lower third and the lower third of the middle third
      of the nose, including the perichondrium and SMAS tissue, we aimed to reduce this
      gap, which has the potential to accumulate soft tissues that cause supratip
      fullness. Between December 2008 and July 2010, the reverse nasal SMAS
      perichondrium flap was used in 42 primary rhinoplasty patients. RESULTS: This
      flap was used in 42 patients. Follow-up ranged from 3 to 18 months. No early or
      late complications were noted, such as infection, excessive bleeding, or extended
      edema. Minor revisions were performed in only two patients with the aim of
      achieving a smoother nasal dorsum. CONCLUSIONS: The reverse nasal SMAS
      perichondrium flap is a new flap. The results presented here are not long term;
      however, the preliminary results are promising. The flap should be avoided in
      cases of thin skin, or at least be used with caution, whereas in thick skin cases
      it is very safe. Further studies in larger groups are required to better define
      the advantages and disadvantages of this flap.

PMID- 21938593
TI  - Reoperative transaxillary breast surgery: using the axillary incision to treat
      augmentation-related complications.
AB  - BACKGROUND: The axillary incision for breast augmentation has been an option for
      patients and surgeons for more than 30 years now. Controlled clinical trials have
      demonstrated that reoperations continue to be significant (15-24% at 3 years)
      independent of incision choice. The misbelief that the transaxillary approach is
      not adequate for reoperations inhibits patients' and surgeons' decisions on what
      incision is best in each case. METHODS: A retrospective analyses was performed
      seeking reoperation cases performed from January 2008 to January 2011 that used
      the same axillary incision as the previous transaxillary augmentation. Data on
      the cause for the reoperation, time between surgeries, patient age, implant
      volume, locality of the primary operation, and details regarding the implant type
      and pocket plane were gathered and analyzed. RESULTS: A total of 15 patients and
      26 breasts needing reoperation were found in this period. The average time
      between the first surgery and reoperation was 12 months, average patient age was
      36 years, and implant volume ranged from 195 to 360 cc, with an average of 283
      cc. Six of these patients were previously operated on by the authors and nine
      were operated on by other surgeons and came to our service seeking revision.
      Details regarding the implant type and pocket plane are also given. The main
      causes for reoperation were capsular contracture (26.9%), size change (15.4%),
      seroma/hematoma (11.5%), infection (11.5%), axillary banding/scarring (11.5%),
      lower-pole deformity/high-riding (11.5%), asymmetry (7.7%), and rippling/waviness
      (3.8%). CONCLUSION: Transaxillary breast augmentation reoperation is feasible if
      certain principles are followed.

PMID- 21938594
TI  - Rhinoplasty sizers.
AB  - Templates and sizers are used as tools to assist in the design and construction
      of both structural and artistic works. These templates and sizers are used
      frequently in the field of aesthetic and reconstructive surgery. The use of a
      template to assist with construction of cartilage grafts in rhinoplasty allows
      the surgeon to sculpt by replicating the template model. Templates and sizers are
      useful and advantageous tools in the rhinoplasty operation.

PMID- 21938595
TI  - Polyamide nanocapsules and nano-emulsions containing Parsol(r) MCX and Parsol(r)
      1789: in vitro release, ex vivo skin penetration and photo-stability studies.
AB  - PURPOSE: To prepare polyamide nanocapsules for skin photo-protection,
      encapsulating alpha-tocopherol, Parsol(r)MCX (ethylhexyl methoxycinnamate) and/or
      Parsol(r)1789 (butyl methoxydibenzoylmethane). METHODS: Nanocapsules were
      obtained by combining spontaneous emulsification and interfacial polycondensation
      reaction between sebacoyl chloride and diethylenetriamine. Nano-emulsions used as
      control were obtained by the same process without monomers. The influence of
      carrier on release rate was studied in vitro with a membrane-free model.
      Epidermal penetration of encapsulated sunscreens was ex vivo evaluated using
      Franz diffusion cells. Ability of encapsulated sunscreens to improve photo
      stability was verified by comparing percentage of degradation after UV radiation
      exposure. RESULTS: Sunscreen-containing nanocapsules (260-400 nm) were
      successfully prepared; yield of encapsulation was >98%. Parsol(r)MCX and
      Parsol(r)1789 encapsulation led to decreased release rate by up to 60% in
      comparison with nano-emulsion and allowed minimum penetration through pig ear
      epidermis. Presence of polyamide shell protected encapsulated sunscreen filters
      from photo-degradation without affecting their activity. CONCLUSIONS:
      Encapsulation of Parsol(r)MCX and Parsol(r)1789 into oil-core of polyamide
      nanocapsules allowed protection from photo-degradation, controlled release from
      nanocapsules, and limited penetration through pig ear epidermis.

PMID- 21938596
TI  - Emerging drugs for cancer-related pain.

PMID- 21938597
TI  - The prevalence and predictive accuracy of quantitatively defined transient
      ischemic dilation of the left ventricle on otherwise normal SPECT myocardial
      perfusion imaging studies.
AB  - AIM: TID in the setting of otherwise normal MPI has been suggested as a marker of
      high risk CAD. In this study we estimate the variance of TID in a normal
      population and the statistical frequency of false positive TID. This will provide
      an indirect measurement of predictive accuracy (PA) in a mixed referral
      population. OBJECTIVE: To study the PA of TID in otherwise normal MPI. METHODS:
      688 consecutive patients were studied. We defined TID according to the standard
      method at 2 cut-off values; 1SD and 2SD, and also by a BSA normalized volume
      difference with gender-specific 2SD limits (NrVD). RESULTS: 457 patients with
      otherwise normal MPI were analyzed. PA of TID at 1SD was 4% and 26% at 2SD. PA
      was slightly higher (42%) using the NrVD, however, still too low to be clinically
      useful as a high-risk marker. PA of TID in patients with perfusion abnormalities
      was 58% at 1SD, 80% at 2SD and slightly higher (93%) by NrVD. CONCLUSIONS: In the
      setting of otherwise normal MPI, elevated TIDr has a low prevalence and poor
      predictive accuracy and should not be considered summarily as a marker of high
      risk CAD.

PMID- 21938598
TI  - Raman spectroscopic analysis of arctic nodules: relevance to the astrobiological
      exploration of Mars.
AB  - The discovery of small, spherical nodules termed 'blueberries' in Gusev Crater on
      Mars, by the NASA rover Opportunity has given rise to much debate on account of
      their interesting and novel morphology. A terrestrial analogue in the form of
      spherical nodules of similar size and morphology has been analysed using Raman
      spectroscopy; the mineralogical composition has been determined and evidence
      found for the biological colonisation of these nodules from the spectral
      signatures of cyanobacterial protective biochemical residues such as scytonemin,
      carotenoids, phycocyanins and xanthophylls. This is an important result for the
      recognition of future sites for the planned astrobiological exploration of
      planetary surfaces using remote robotic instrumentation in the search for extinct
      and extant life biosignatures and for the expansion of putative terrestrial Mars
      analogue geological niches and morphologies.

PMID- 21938599
TI  - Healthy Lungs: cancer education for middle school teachers using a "train and
      equip" method.
AB  - Prevention of the initiation of tobacco use, which is associated with increased
      risk of developing cancer of the lung, the oral cavity, larynx, and emphysema,
      should target middle school-age children because that is where experimentation
      with tobacco use usually begins. Millions of children attending school do not
      receive proper education regarding the biological science of the human
      respiratory system coupled with the impact that tobacco use has at the cell,
      tissue, and organ levels of biological organization because their teachers are
      ill-prepared and ill-equipped to teach this normal and cancer-related content.
      The University of Arkansas for Medical Sciences has a statewide outreach program
      that provides middle school teachers training in a "Healthy Lungs" curriculum
      that covers the normal functional anatomy of the respiratory system as a basis
      for adding the effect of tobacco use and its associated cancers and emphysema.
      This training also provides each participant a resource kit of supplies,
      materials, and items of equipment. A long-term implementation survey identified a
      high degree of transference of content and use of the resource kit items into new
      classroom learning activities for the trainee's students for both the normal
      functional anatomy of the human respiratory system and associated general and
      cell/tissue/organ-specific cancer biology.

PMID- 21938600
TI  - "The promise of community-based advocacy and education efforts for increasing
      cancer clinical trials accrual".
AB  - Only 3% of cancer patients participate in cancer clinical trials (CCTs). A number
      of barriers to participation, particularly for minority groups, can be addressed
      through community-focused education and advocacy efforts. Working with community
      partnerships, a pilot program sought to change knowledge, attitudes, and role
      behaviors among community leaders, primary care providers (PCPs), and clinical
      researchers about CCTs, to increase patient awareness of and participation in
      CCTs. A mixed method evaluation utilized quantitative analysis of surveys
      administered to participants during the program period (2006-2008) and
      qualitative data from interviews with key participants. Programmatic efforts were
      effective in increasing knowledge and training community leaders and PCPs to
      disseminate messages about clinical trials, and ultimately increasing patient
      inquiries about local trials. Training improved cultural competency skills among
      clinical researchers to recruit and retain CCT participants. Partnerships
      fostered new processes and structures to facilitate CCT participation in their
      communities. Clinical trials education and advocacy efforts through community
      partnerships have an important role in enhancing clinical trial access and in
      increasing clinical trial participation. Oncologists' involvement in and
      leadership of such partnerships are critical to promoting CCT accrual,
      particularly for minority groups.

PMID- 21938601
TI  - [Knee disarticulation and through-knee amputation].
AB  - OBJECTIVE: A knee disarticulation or a through-knee stump is superior compared to
      a transfemoral stump. The thigh muscles are all preserved, and the muscle balance
      remains undisturbed. The range of motion of the hip joint is not limited. The
      bulbous shape of the stump allows full weight bearing at the stump end and can
      easily be fitted with a prosthesis. An amputee with a bilateral knee
      disarticulation is able to walk "barefoot". INDICATIONS: A more distal amputation
      level, e.g., an ultra-short transtibial amputation, is not possible. Important
      alternative to transfemoral amputations. Possible for any etiology except for
      Buerger-Winiwarter's disease. New indications are infected and loosened total
      knee replacements. CONTRAINDICATIONS: Preservation of the knee joint is possible.
      SURGICAL TECHNIQUE: Knee disarticulation is a very atraumatic procedure, compared
      to transfemoral amputations. Neither bones nor muscles have to be severed, just
      skin, ligaments, vessels, and nerves. Even the meniscal cartilages may be left in
      place to act as axial shock absorbers. The cartilage of the femur is not
      resected, but only bevelled in case of osteoarthritis. There are no tendon
      attachments or myoplastic procedures necessary. The patella remains in place and
      is held in position only by the retinacula. Skin closure must be performed
      without the slightest tension, and if possible not in the weight-bearing area.
      Transcondylar amputations across the femoral condyles only are indicated when
      there are not sufficient soft tissues for wound closure of a knee
      disarticulation. Alternatives as the techniques of Gritti, Klaes, and Eigler, the
      shortening of the femur and the Sauerbruch's rotation plasty [14] are presented
      and discussed. POSTOPERATIVE MANAGEMENT: The risk of decubital ulcers is rather
      high. Correct bandaging of the stump is, therefore, particularly important.
      Prosthetic fitting is possible 3-6 weeks after surgery. The type of prosthesis
      depends on the amputee's activity level. RESULTS: The superior performance of
      amputees with knee disarticulations in sports prove the superiority of that
      amputation level compared to transfemoral amputees. However, because less than 5%
      of amputations are knee disarticulations, statements about statistical
      significance cannot be made. On the other hand, one should do everything to
      preserve an ultra-short transtibial stump.

PMID- 21938602
TI  - The cost of screening and brief intervention in employee assistance programs.
AB  - Few studies examine the costs of conducting screening and brief intervention
      (SBI) in settings outside health care. This study addresses this gap in knowledge
      by examining the employer-incurred costs of SBI in an employee assistance program
      (EAP) when delivered by counselors. Screening was self-administered as part of
      the intake paperwork, and the brief intervention (BI) was delivered during a
      regular counseling session. Training costs were $83 per counselor. The cost of a
      screen to the employer was $0.64; most of this cost comprised the cost of the
      time the client spent completing the screen. The cost of a BI was $2.52. The cost
      of SBI is lower than cost estimates of SBI conducted in a health care setting.
      The low costs for the current study suggest that only modest gains in outcomes
      would likely be needed to justify delivering SBI in an EAP setting.

PMID- 21938603
TI  - [Guidelines - whom do they help?].

PMID- 21938604
TI  - [Epidural spinal cord stimulation for therapy of chronic pain. Summary of the S3
      guidelines].
AB  - Epidural spinal cord stimulation (SCS) is a reversible but invasive procedure
      which should be used for neuropathic pain, e.g. complex regional pain syndrome I
      (CRPS) and for mostly chronic radiculopathy in connection with failed back
      surgery syndrome following unsuccessful conservative therapy. Epidural SCS can
      also successfully be used after exclusion of curative procedures and conservative
      therapy attempts for vascular-linked pain, such as in peripheral arterial
      occlusive disease stages II and III according to Fontaine and refractory angina
      pectoris. Clinical practice has shown which clinical symptoms cannot be
      successfully treated by epidural SCS, e.g. pain in complete paraplegia syndrome
      or atrophy/injury of the sensory pathways of the spinal cord or cancer pain. A
      decisive factor is a critical patient selection as well as the diagnosis.
      Epidural SCS should always be used within an interdisciplinary multimodal therapy
      concept. Implementation should only be carried out in experienced therapy centers
      which are in a position to deal with potential complications.

PMID- 21938605
TI  - [Optimized assessment of the outcome in patients with radicular back pain of the
      lumbar spine. The modified NASS questionnaire].
AB  - BACKGROUND: The purpose of the study was to present a reliable instrument with
      easy application to assess the outcome and improvement of therapy in patients
      with radicular symptoms of the lumbar spine. METHODS: Data from patients who
      underwent microdiscectomy because of lumbar radicular symptoms were collected and
      analyzed and interviews were performed using the well-known North American Spine
      Society (NASS) lumbar spine questionnaire (17 items) before and after the
      intervention. In addition patient data including comorbidities were collected. By
      calculating effect size (ES) and standardized response mean (SRM) for each item
      of the questionnaire, the questions with the highest change before and after the
      intervention could be selected. RESULTS: A total of 139 patients undergoing
      microdiscectomy for lumbar radicular symptoms due to a disc herniation were
      included in the analysis. Concerning the three dimensions pain, neurological
      symptoms and impairment of activities in daily life, the questions with best
      predictive value (high ES and SRM) were selected. According to their clinical
      relevance eight questions of the NASS questionnaire were finally selected for the
      short form. CONCLUSION: This short, significant and easy to use questionnaire is
      in our opinion a useful instrument to assess the course of patients with
      radicular back pain and especially to measure and monitor the outcome of
      therapeutic interventions, in addition to conventional clinical diagnostics and
      examinations. This novel instrument could be a useful tool for improving quality
      assurance in conventional and interventional pain management of these patients.

PMID- 21938606
TI  - [Botulinum toxin type A in the prophylactic treatment of chronic migraine].
AB  - Since the second edition of the International classification of headache
      disorders (ICDH-II 2004), chronic migraine has been listed amongst migraine
      complications. Compared to episodic migraine the prevalence of chronic migraine
      is low, its impact, however, significant. Until recently no prophylactic drug had
      been approved for chronic migraine prophylaxis. After case reports had stated an
      effect of botulinum toxin type A on migraine, several randomized placebo
      controlled studies were conducted in episodic headache; the results, however,
      were disappointing. Only when botulinum toxin type A was used in chronic migraine
      in the PREEMPT (phase 3 research evaluating migraine prophylaxis therapy) trials,
      its superiority compared to placebo was established. Thus, for the first time a
      prophylactic drug against chronic migraine is available which is both effective
      and well tolerated. Botox(r) has been licensed in England for the prophylaxis of
      headaches in adults with chronic migraine in 2010. Approval for its use in
      Germany has been applied for.

PMID- 21938610
TI  - Percutaneous left atrial appendage closure.

PMID- 21938611
TI  - Glass physics: from fundamentals to applications.

PMID- 21938612
TI  - Kinetic fragility of binary and ternary glass forming liquid mixtures.
AB  - The experimental studies of liquid fragility in miscible binary and ternary glass
      forming mixtures reveal a general observation of the negative deviation in
      fragility upon mixing from the linear average of those of the components. Further
      analyses from ideal, near ideal to non-ideal mixing modes show that the deviation
      magnitude does not increase monotonically with mixing enthalpy, and a moderate
      intermolecular interaction would generate a largest reduction in fragility. Four
      eutectic systems, methyl-o-toluate-methyl-p-toluate, ZnCl(2)-AlCl(3), glycerol
      water, and fructose-water, are studied to locate the composition where the
      largest fragility deviation occurs in phase diagrams. It is found that the
      compositions with the fragility minima do not coincide with the eutectic points.
      The results partly explain the experimental observation that the best glass
      forming region is not located at the eutectic composition.

PMID- 21938613
TI  - SAXS study on myoglobin embedded in amorphous saccharide matrices.
AB  - We report on Small Angle X-ray Scattering (SAXS) measurements performed on
      samples of carboxy-myoglobin and met-myoglobin embedded in low hydrated matrices
      of four different saccharides (trehalose, sucrose, maltose and lactose). Results
      confirm the already reported occurrence of inhomogeneities, which are not
      peculiar of trehalose samples, but appear also in maltose and lactose, and in
      some cases also sucrose, being dependent on the sample hydration and on the
      presence of sodium dithionite. This behaviour confirms our previous
      interpretation about the nature of the inhomogeneities, and prompt it as a
      possible general behaviour for highly concentrated sugar matrices.

PMID- 21938614
TI  - Bethe-Peierls approximation for linear monodisperse polymers re-examined.
AB  - Bethe-Peierls approximation, as it applies to the thermodynamics of polymer
      melts, is reviewed. We compare the computed configurational entropy of
      monodisperse linear polymer melt with Monte Carlo data available in the
      literature. An estimation of the configurational contribution to the total
      liquid's C(p) is presented. We also discuss the relation between the Kauzmann
      paradox and polymer semiflexibility.

PMID- 21938615
TI  - Temperature behavior of the Kohlrausch exponent for a series of vinylic polymers
      modelled by an all-atomistic approach.
AB  - The Kohlrausch-Williams-Watt (KWW) function, or stretched exponential function,
      is usually employed to reveal the time dependence of the polymer backbone
      relaxation process, the so-called alpha relaxation, at different temperatures. In
      order to gain insight into polymer dynamics at temperatures higher than the glass
      transition temperature T(g), the behavior of the Kohlrausch exponent, which is a
      component of the KWW function, is studied for a series of vinylic polymers, using
      an all-atomistic simulation approach. Our data show very good agreement with
      published experimental results and can be described by existing phenomenological
      models. The Kohlrausch exponent exhibits a linear dependence with temperature
      until it reaches a constant value of 0.44, at 1.26T(g), revealing the existence
      of two regimes. These results suggest that, as the temperature increases, the
      dynamics progressively change until it reaches a plateau. The non-exponential
      character then describes subdiffusive motion characteristic of polymer melts.

PMID- 21938616
TI  - Tagged-particle motion in glassy systems under shear: Comparison of mode coupling
      theory and Brownian dynamics simulations.
AB  - We study the dynamics of a tagged particle in a glassy system under shear. The
      recently developed integration through transients approach, based on mode
      coupling theory, is continued to arrive at the equations for the tagged-particle
      correlators and the mean squared displacements. The equations are solved
      numerically for a two-dimensional system, including a nonlinear stability
      analysis of the glass solution, the so called beta-analysis. We perform Brownian
      Dynamics simulations in 2D and compare with theory. After switch on, transient
      glassy correlation functions show strong fingerprints of the stress overshoot
      scenario, including, additionally to previously studied superexponential decay, a
      shoulder-like slowing down after the overshoot. We also find a new type of Taylor
      dispersion in glassy states which has intriguing similarity to the known low
      density case. The theory qualitatively captures most features of the simulations
      with quantitative deviations concerning the shear-induced time scales. We
      attribute these deviations to an underestimation of the overshoot scenario in the
      theory.

PMID- 21938617
TI  - How do you find transcription factors? Computational approaches to compile and
      annotate repertoires of regulators for any genome.
AB  - Transcription factors (TFs) play an important role in regulating gene expression.
      The availability of complete genome sequences and associated functional genomic
      data offer excellent opportunities to understand the transcriptional regulatory
      system of an entire organism. To do so, however, it is essential to compile a
      reliable dataset of regulatory components. Here, we review computational methods
      and publicly accessible resources that help identify TF-coding genes in
      prokaryotic and eukaryotic genomes. Since the regulatory functions of most TFs
      remain unknown, we also discuss approaches for combining diverse genomic datasets
      that will help elucidate their chromosomal organisation, expression, and
      evolutionary conservation. These analysis methods provide a solid foundation for
      further investigations of the transcriptional regulatory system.

PMID- 21938618
TI  - Expression pattern analysis of regulatory transcription factors in Caenorhabditis
      elegans.
AB  - Expression pattern data are fundamental to understanding transcriptional
      regulatory networks and the biological significance of such networks. For
      Caenorhabditis elegans, expression pattern analysis of transcription factor
      genes, with cellular resolution, typically involves generation of transcription
      factor gene/reporter gene fusions. This is followed by the creation of C. elegans
      strains transgenic for, and determination of expression patterns driven by, these
      fusions. Physiologically relevant regulatory relationships between transcription
      factors are both inferred from their expression patterns, in combination with
      protein-DNA interaction data, and evidenced from alterations of expression
      patterns when networks are disturbed.

PMID- 21938619
TI  - High-throughput SELEX determination of DNA sequences bound by transcription
      factors in vitro.
AB  - SELEX (systematic evolution of ligands by exponential enrichment) was created 20
      years ago as a method to enrich small populations of bound DNAs from a random
      sequence pool by PCR amplification. It provides a powerful way to determine the
      in vitro binding specificities of DNA-binding proteins such as transcription
      factors. Here, we present a robust version of the SELEX protocol for high
      throughput analysis. Protein-bound beads prepared from insoluble recombinant 6*
      HIS-tagged transcription factor protein are used in a simple pull-down assay. To
      allow efficient determination of the enriched DNA sequences, bound
      oligonucleotides are concatenated, allowing approximately 1,000 oligonucleotides
      to be sequenced from one 96-well format plate. Successive rounds of SELEX data
      are statistically useful for understanding the full range of moderate affinity
      and high-affinity binding sites.

PMID- 21938620
TI  - Convenient determination of protein-binding DNA sequences using quadruple 9-mer
      based microarray and DsRed-monomer fusion protein.
AB  - Protein-binding DNA microarray (PBM) is one of the high-throughput methods to
      define DNA sequences which potentially bind to a given DNA-binding protein.
      Quadruple 9-mer-based protein-binding DNA microarray, named Q9-PBM, is designed
      in such a way that target probes are synthesized as quadruples of all possible 9
      mer combinations. Also, recombinant proteins fused with DsRed-monomer fluorescent
      protein are conveniently constructed. Q9-PBM confirms the well-known DNA-binding
      sequences of Cbf1 and CBF1/DREB1B transcription factors, and also identifies the
      adjacent sequences. Moreover, Q9-PBM is applied to elucidate the unidentified cis
      acting element of the OsNAC6 rice transcription factor. This technology will
      facilitate greater understanding of genome-wide interactions between proteins and
      DNA.

PMID- 21938621
TI  - Analysis of specific protein-DNA interactions by bacterial one-hybrid assay.
AB  - The DNA-binding specificity of transcription factors allows the prediction of
      regulatory targets in a genome. However, very few factor specificities have been
      characterized and still too little is known about how these proteins interact
      with their targets to make predictions a priori. To provide a greater
      understanding of how proteins and DNA interact, we have developed a bacterial one
      hybrid system that allows the sensitive, high-throughput, and cost-effective
      assay of the interaction at the protein-DNA interface. This system makes survival
      of the bacteria dependent on activation of the reporter gene and therefore
      dependent on the protein-DNA interaction that recruits the polymerase. We have
      used this system to characterize DNA-binding specificities for representative
      members of the most common DNA-binding domain (DBD) families. We have also been
      able to engineer DBDs with novel specificity to be used as artificial
      transcription factors and zinc finger nucleases. The B1H assay provides a simple
      and inexpensive method to investigate protein-DNA interactions that is accessible
      to essentially any laboratory.

PMID- 21938622
TI  - MITOMI: a microfluidic platform for in vitro characterization of transcription
      factor-DNA interaction.
AB  - Gene regulatory networks (GRNs) consist of transcription factors (TFs) that
      determine the level of gene expression by binding to specific DNA sequences.
      Mapping all TF-DNA interactions and elucidating their dynamics is a major goal to
      generate comprehensive models of GRNs. Measuring quantitative binding affinities
      of large sets of TF-DNA interactions requires the application of novel tools and
      methods. These tools need to cope with the difficulties related to the facts that
      TFs tend to be expressed at low levels in vivo, and often form only transient
      interactions with both DNA and their protein partners. Our approach describes a
      high-throughput microfluidic platform with a novel detection principle based on
      the mechanically induced trapping of molecular interactions (MITOMI). MITOMI
      allows the detection of transient and low-affinity TF-DNA interactions in high
      throughput.

PMID- 21938623
TI  - Detecting protein-protein interactions with the Split-Ubiquitin sensor.
AB  - A detailed understanding of a cellular process requires the knowledge about the
      interactions between its protein constituents. The Split-Ubiquitin technique
      allows to monitor and detect interactions of very diverse proteins, including
      transcription factors and membrane-associated proteins. The technique is based on
      unique features of ubiquitin, the enzymes of the ubiquitin pathway, and the
      reconstitution of a native-like ubiquitin from its N- and C-terminal fragments.
      Using Ura3p as a reporter for the reconstitution of the ubiquitin fragments,
      methods are presented that enable to screen in yeast for interaction partners of
      a given protein with either a randomly generated expression library or a defined
      but more limited array of protein fusions.

PMID- 21938624
TI  - Genome-wide dissection of posttranscriptional and posttranslational interactions.
AB  - Transcriptional interactions in the cell are modulated by a variety of
      posttranscriptional and posttranslational mechanisms that make them highly
      dependent on the molecular context of the specific cell. These include, among
      others, microRNA-mediated control of transcription factor (TF) mRNA translation
      and degradation, transcription factor activation by phosphorylation and
      acetylation, formation of active complexes with one or more cofactors, and
      mRNA/protein degradation and stabilization processes. Thus, the ability of a
      transcription factor to regulate its targets depends on a variety of genetic and
      epigenetic mechanisms, resulting in highly context-dependent regulatory networks.
      In this chapter, we introduce a step-by-step guide on how to use the MINDy
      systems biology algorithm (Modulator Inference by Network Dynamics) that we
      recently developed, for the genome-wide, context-specific identification of
      posttranscriptional and posttranslational modulators of transcription factor
      activity.

PMID- 21938625
TI  - Linking cellular signalling to gene expression using EXT-encoded reporter
      libraries.
AB  - Intracellular signalling initiated by extracellular ligands that activate cell
      surface receptors is a complicated process that involves multiple interconnected
      biochemical steps. Protein-protein interactions are often regulated by activated
      kinases via phosphorylation of specific residues. Such transient regulated
      interactions are central to many signalling cascades. Downstream signalling
      converges at the level of transcription factors to finally regulate adaptive
      transcriptional responses. There are powerful methods available to study
      transcriptional changes even at a global level; however, measuring upstream
      regulatory mechanisms is still challenging. We designed an experimental approach
      termed expressed oligonucleotide tag (EXT)assay that enables the parallel
      analysis of signalling events upstream of gene expression. We make use of
      different types of reporter gene assays that are invariably linked to unique EXTs
      serving as quantitative decoders of respective assays. EXT reporters can be
      introduced into living cells and analyzed in pools by microarray hybridization or
      sequencing.

PMID- 21938626
TI  - Sample preparation for small RNA massive parallel sequencing.
AB  - High-throughput sequencing has allowed for a comprehensive small RNA (sRNA)
      expression analysis of numerous tissues in a diverse set of organisms. The
      computational analysis of the millions of generated sequencing reads has led to
      the discovery of novel miRNAs and other sRNA species, and resulted in a better
      understanding of the roles these sRNAs play in development and disease. This
      chapter describes the generation of sRNA deep-sequencing libraries for the
      Illumina massively parallel sequencing platform by using a cloning method that
      anneals specific RNA sequences to the 5'- and 3'-ends of the sRNA molecules.

PMID- 21938627
TI  - CAGE (cap analysis of gene expression): a protocol for the detection of promoter
      and transcriptional networks.
AB  - We provide here a protocol for the preparation of cap-analysis gene expression
      (CAGE) libraries, which allows for measuring the expression of eukaryotic capped
      RNAs and simultaneously map the promoter regions. The presented protocol
      simplifies the previously published ones and moreover produces tags that are 27
      nucleotides long, which facilitates mapping to the genome. The protocol takes
      less than 5 days to complete and presents a notable improvement compared to
      previously published versions.

PMID- 21938628
TI  - Detecting DNaseI-hypersensitivity sites with MLPA.
AB  - DNaseI-hypersensitive sites within chromatin are indicative of genomic loci with
      regulatory function. Several techniques have been described for analyzing these
      regions, but are either laborious, offer low-throughput possibilities, or are
      expensive. We have developed a new approach based on a modified version of
      multiplex ligation-dependent probe amplification (MLPA). Using this method, it is
      possible to analyse up to 50 defined genomic regions for DNaseI-hypersensitivity
      in a single PCR-based reaction. This chapter outlines the approach and discusses
      the critical features of each step of the procedure.

PMID- 21938629
TI  - Detecting long-range chromatin interactions using the chromosome conformation
      capture sequencing (4C-seq) method.
AB  - Eukaryotic transcription is tightly regulated by transcriptional regulatory
      elements, even though these elements may be located far away from their target
      genes. It is now widely recognized that these regulatory elements can be brought
      in close proximity through the formation of chromatin loops, and that these loops
      are crucial for transcriptional regulation of their target genes. The chromosome
      conformation capture (3C) technique presents a snapshot of long-range
      interactions, by fixing physically interacting elements with formaldehyde,
      digestion of the DNA, and ligation to obtain a library of unique ligation
      products. Recently, several large-scale modifications to the 3C technique have
      been presented. Here, we describe chromosome conformation capture sequencing (4C
      seq), a high-throughput version of the 3C technique that combines the 3C-on-chip
      (4C) protocol with next-generation Illumina sequencing. The method is presented
      for use in mammalian cell lines, but can be adapted to use in mammalian tissues
      and any other eukaryotic genome.

PMID- 21938630
TI  - Analyzing transcription factor occupancy during embryo development using ChIP
      seq.
AB  - Accurately assessing the binding of transcription factors to cis-regulatory
      elements in vivo is an essential step toward understanding the mechanisms that
      govern embryonic development. Genome-wide transcription factor location analysis
      has been facilitated by the development of high-density tiling arrays (ChIP-on
      chip), and more recently by next-generation sequencing technologies, which are
      used to sequence the DNA fragments obtained from chromatin immunoprecipitation
      experiments (ChIP-seq). This chapter provides a detailed protocol of the
      different steps required to generate a successful ChIP-seq library, starting from
      embryo collection and fixation to chromatin preparation, immunoprecipitation, and
      finally library preparation. The protocol is optimized for Drosophila embryos,
      but can be adapted to any organism. The obtained library is suitable for
      sequencing on an Illumina GAIIx platform.

PMID- 21938631
TI  - Genome-wide profiling of DNA-binding proteins using barcode-based multiplex
      Solexa sequencing.
AB  - Chromatin immunoprecipitation (ChIP) is a commonly used technique to detect the
      in vivo binding of proteins to DNA. ChIP is now routinely paired to microarray
      analysis (ChIP-chip) or next-generation sequencing (ChIP-Seq) to profile the DNA
      occupancy of proteins of interest on a genome-wide level. Because ChIP-chip
      introduces several biases, most notably due to the use of a fixed number of
      probes, ChIP-Seq has quickly become the method of choice as, depending on the
      sequencing depth, it is more sensitive, quantitative, and provides a greater
      binding site location resolution. With the ever increasing number of reads that
      can be generated per sequencing run, it has now become possible to analyze
      several samples simultaneously while maintaining sufficient sequence coverage,
      thus significantly reducing the cost per ChIP-Seq experiment. In this chapter, we
      provide a step-by-step guide on how to perform multiplexed ChIP-Seq analyses. As
      a proof-of-concept, we focus on the genome-wide profiling of RNA Polymerase II as
      measuring its DNA occupancy at different stages of any biological process can
      provide insights into the gene regulatory mechanisms involved. However, the
      protocol can also be used to perform multiplexed ChIP-Seq analyses of other DNA
      binding proteins such as chromatin modifiers and transcription factors.

PMID- 21938632
TI  - Computational analysis of protein-DNA interactions from ChIP-seq data.
AB  - Chromatin immunoprecipitation experiments followed by ultra-high-throughput
      sequencing (ChIP-seq) is becoming the method of choice to identify transcription
      factor binding sites in prokaryotes and eukaryotes in vivo. Here, we review the
      computational steps that are necessary for analyzing the sequenced chromatin
      fragments, including mapping of short reads onto reference genomes, normalization
      of multiple conditions, detection of bona fide peaks or binding sites, annotation
      of sites, characterization of sequence-specific binding affinities, and
      relationships with biophysical models for protein-DNA interactions. The goal is
      that following the indicated steps will help the discovery of novel mechanisms
      underlying transcription regulation in a broad range of experimental systems.

PMID- 21938633
TI  - Using a yeast inverse one-hybrid system to identify functional binding sites of
      transcription factors.
AB  - Binding of transcription factors to promoters is a necessary step to initiate
      transcription. From an evolutionary standpoint, the regulatory proteins and their
      binding sites are considered to have molecularly coevolved. We developed an
      efficient yeast strategy, an "inverse one-hybrid system", to identify binding
      targets of transcription factors globally in a genome of interest. The technique
      consists of a yeast strain expressing a -transcription factor of interest mated
      to yeast containing a library of random genomic fragments cloned upstream of a
      reporter gene (URA3). Positive growth on media without uracil denotes a fragment
      being bound by the transcription factor, e.g., zebrafish FoxI1. The bound
      fragments in hundreds of positive clones are sequenced and retested for their
      binding activities using a colony PCR and sequencing strategy. The resulting
      tools allow for rapid and genomic-wide identification of transcriptional binding
      targets.

PMID- 21938634
TI  - Using cisTargetX to predict transcriptional targets and networks in Drosophila.
AB  - Gene expression regulation is a fundamental biological process leading to
      complete organism development by controlling processes like cell type
      specification and differentiation. The accuracy of this process is -governed by
      transcription factors (TFs) acting within a complex gene regulatory network.
      CisTargetX has been developed to enable a user to predict TFs, enhancers, and
      target genes involved in the regulation of co-expressed genes. It uses a strategy
      that incorporates the genome-wide prediction of clusters of transcription factor
      binding sites (TFBSs), starting from a large, unbiased collection of position
      weight matrices (PWMs) and uses comparative genomics criteria to filter potential
      TFBS. We describe in this chapter, step-by-step, how to use cisTargetX starting
      from a set of genes or TF(s) to predict transcriptional targets with their
      putative binding sites and networks in Drosophila. Next, we illustrate this
      approach on a particular developmental system, namely, sensory organ development,
      and identify relevant TFs, DNA regions regulating gene expression, and TF/target
      gene interactions. CisTargetX is available at
      http://med.kuleuven.be/lcb/cisTargetX .

PMID- 21938635
TI  - Proteomic methodologies to study transcription factor function.
AB  - Transcription factors regulate transcription by binding to regulatory regions of
      genes including the promoter. Few of the transcription factors are well
      characterized, and few promoters have been described in detail. New methods have
      been developed to improve both transcription factor and promoter
      characterization, some of which are discussed here. Trapping methodology
      applicable to both individual transcription factors and intact transcription
      complexes are described, as well as 2D gel electrophoresis, Southwestern
      blotting, and basic liquid chromatography/tandem mass spectrometry methodology.
      These methods have proved useful in the study of transcriptional regulation.

PMID- 21938636
TI  - A high-throughput gateway-compatible yeast one-hybrid screen to detect protein
      DNA interactions.
AB  - In recent years, new techniques have spurred the discovery of cis-regulatory DNA
      elements. These stretches of noncoding DNA contain combinations of recognition
      sites to which transcription factors (TFs) bind, and in doing so, these TFs can
      activate or repress transcription. These protein-DNA interactions form the core
      of gene regulatory networks (GRNs) that are responsible for the differential gene
      expression that allow diversification of cell types, developmental programs, and
      responses to the environment. The yeast one-hybrid system is a genetic assay to
      identify direct binding of proteins to DNA elements of interest and is,
      therefore, instrumental in uncovering these GRNs.

PMID- 21938637
TI  - BioTapestry: a tool to visualize the dynamic properties of gene regulatory
      networks.
AB  - BioTapestry is an open source, freely available software tool that has been
      developed to handle the -challenges of modeling genetic regulatory networks
      (GRNs). Using BioTapestry, a researcher can -construct a network model and use it
      to visualize and understand the dynamic behavior of a complex, spatially and
      temporally distributed GRN. Here we provide a step-by-step example of a way to
      use BioTapestry to build a GRN model and discuss some common issues that can
      arise during this process.

PMID- 21938638
TI  - Implicit methods for qualitative modeling of gene regulatory networks.
AB  - Advancements in high-throughput technologies to measure increasingly complex
      biological phenomena at the genomic level are rapidly changing the face of
      biological research from the single-gene single-protein experimental approach to
      studying the behavior of a gene in the context of the entire genome (and
      proteome). This shift in research methodologies has resulted in a new field of
      network biology that deals with modeling cellular behavior in terms of network
      structures such as signaling pathways and gene regulatory networks. In these
      networks, different biological entities such as genes, proteins, and metabolites
      interact with each other, giving rise to a dynamical system. Even though there
      exists a mature field of dynamical systems theory to model such network
      structures, some technical challenges are unique to biology such as the inability
      to measure precise kinetic information on gene-gene or gene-protein interactions
      and the need to model increasingly large networks comprising thousands of nodes.
      These challenges have renewed interest in developing new computational techniques
      for modeling complex biological systems. This chapter presents a modeling
      framework based on Boolean algebra and finite-state machines that are reminiscent
      of the approach used for digital circuit synthesis and simulation in the field of
      very-large-scale integration (VLSI). The proposed formalism enables a common
      mathematical framework to develop computational techniques for modeling different
      aspects of the regulatory networks such as steady-state behavior, stochasticity,
      and gene perturbation experiments.

PMID- 21938639
TI  - Commentary: do we have a consistent terminology for species diversity? We are on
      the way.
AB  - A consistent terminology for species diversity is subject of an ongoing debate.
      Recently Tuomisto (Oecologia 164:853-860, 2010) stated that a consistent
      terminology for diversity already exists. The paper comments on recent papers by
      ourselves (Jurasinski et al. Oecologia 159:15-26, 2009) and by Moreno and
      Rodriguez (Oecologia 163:279-282, 2010). Both started from Whittaker's diversity
      concept to discuss the ambiguities of the terminology and propose a new, more
      consistent terminology that is based on the different approaches to diversity
      analysis. In contrast, Tuomisto adheres to a strict school of thinking and
      derives a diversity framework in the sense of Whittaker (alpha, beta, gamma) from
      the conceptual definition of diversity itself. A third group of papers discusses
      appropriate methods for the analysis of the variation in species composition.
      Here, we support the idea that alpha, beta and gamma diversity should be used in
      a strict sense that is based only on the conceptual definition of diversity. We
      accordingly extend and modify our terminological concept for species diversity.
      All approaches to the analysis and quantification of species composition and
      diversity can be assigned to three abstraction levels (species composition,
      variation in species composition,and variation in variation in species
      composition) and two scale levels (sample scale, aggregation scale). All methods
      that investigate the variation in species composition across scale levels
      evaluate beta relation with beta diversity being just one form of beta relation,
      which is calculated by dividing gamma diversity of order q by the appropriate
      alpha diversity of the same order. In contrast, differentiation refers to a
      pairwise calculation of resemblance in species composition. It is restricted to
      sample scale and is therefore most often only an intermediate step of analysis.
      Many ecological questions can be addressed either by direct analysis of the
      variation in species composition using raw data approaches or by further analysis
      of differentiation datasets on aggregation scale with or without respect to an
      external gradient.

PMID- 21938640
TI  - Humic analog AQDS and AQS as an electron mediator can enhance chromate reduction
      by Bacillus sp. strain 3C3.
AB  - Humus as an electron mediator is recognized as an effective strategy to improve
      the biological transformation and degradation of toxic substances, yet the action
      of humus in microbial detoxification of chromate is still unknown. In this study,
      a humus-reducing strain 3C(3) was isolated from mangrove sediment. Based on the
      analyses of morphology, physiobiochemical characteristics, and 16S rRNA gene
      sequence, this strain was identified Bacillus sp. Strain 3C(3) can effectively
      reduce humic analog anthraquinone-2,6-disulfonate (AQDS) and anthraquinone-2
      sulfonate (AQS) with lactate, formate, or glucose as electron donors. When the
      cells were killed by incubation at 95 degrees C for 30 min or an electron donor
      was absent, the humic reduction did not occur, showing that the humic reduction
      was a biochemical process. However, strain 3C(3) had low capability of chromate
      reduction under anaerobic conditions, despite of having strong tolerance of the
      toxic metal. But in the presence of humic substances AQDS or AQS, we found that
      chromate reduction by strain 3C(3) was enhanced greatly. Because strain 3C(3) is
      an effective humus-reducing bacterium, it is proposed that humic substances could
      serve as electron mediator to interact with chromate and accelerate chromate
      reduction. Our results suggest that chromate contaminations can be detoxified by
      adding humic analog (low to 0.1 mM) as an electron mediator in the microbial
      incubation.

PMID- 21938641
TI  - The impact of auditory distraction on retrieval of visual memories.
AB  - Recent research has revealed that the presence of irrelevant visual information
      during retrieval of long-term memories diminishes recollection of task-relevant
      visual details. Here, we explored the impact of irrelevant auditory information
      on remembering task-relevant visual details by probing recall of the same
      previously viewed images while participants were in complete silence, exposed to
      white noise, or exposed to ambient sounds recorded at a busy cafe. The presence
      of auditory distraction diminished objective recollection of goal-relevant
      details, relative to the silence and white noise conditions. Critically, a
      comparison with results from a previous study using visual distractors showed
      equivalent effects for auditory and visual distraction. These findings suggest
      that disruption of recollection by external stimuli is a domain-general
      phenomenon produced by interference between resource-limited, top-down mechanisms
      that guide the selection of mnemonic details and control processes that mediate
      our interactions with external distractors.

PMID- 21938642
TI  - I said, you said: the production effect gets personal.
AB  - Saying a word out loud makes it more memorable than simply reading it silently.
      This robust finding has been labeled the production effect and has been
      attributed to the enhanced distinctiveness of produced relative to unproduced
      items (MacLeod et al. Journal of Experimental Psychology: Learning, Memory, and
      Cognition, 36, 671-685, 2010). Produced items have the additional information
      that they were spoken aloud encoded in their representations, and this
      information is useful during retrieval in certifying prior encoding. The present
      study explored whether production must be self-performed to be beneficial, or
      whether another person's production also makes an item more memorable. In two
      experiments, the production effect was shown to be reliable when production was
      done by someone other than the rememberer (i.e., by the experimenter or by
      another participant), but substantially smaller than the benefit from self
      performed production. Intriguingly, the effect was intermediate when production
      was done by both the rememberer and another person. Distinctiveness--and hence
      the production effect--is greatest to the extent that it is personal.

PMID- 21938643
TI  - The associations among coping, nadir CD4+ T-cell count, and non-HIV-related
      variables with health-related quality of life among an ambulatory HIV-positive
      patient population.
AB  - PURPOSE: We investigated HRQoL among HIV-positive outpatients from October, 2006
      December, 2007, incorporating medical chart review, and a survey of coping
      styles. METHODS: Consented HIV-positive patients receiving medical care at
      University of Colorado Denver, with HAART as first antiretroviral regimen,
      completed the MOS-HIV and Brief COPE survey instruments. Linear regression
      identified a priori factors hypothesized to be associated with the MOS-HIV
      composite mental and physical health scores (MHS, PHS). Brief COPE survey
      maladaptive and adaptive coping components were added to the models and retained
      if significant. RESULTS: Among the 157 patient cohort, parsimonious multivariable
      linear regression models (P < 0.05) indicated higher nadir CD4+ T-cell counts and
      adaptive coping were associated with a higher MHS; public/no insurance, mental
      illness, current number of non-HIV medications, and maladaptive coping were
      inversely associated with MHS. Nadir CD4+ T-cell count and efavirenz use were
      associated with a higher PHS; mental illness, current number of non-HIV
      mediations, and maladaptive coping were inversely associated with PHS.
      CONCLUSIONS: Factors independently associated with lower MHS and lower PHS
      include lower nadir CD4+ T-cell counts, and use of maladaptive coping. Efforts to
      reduce use of maladaptive coping strategies and earlier identification and
      treatment of HIV may improve HRQoL in HIV-positive patients.

PMID- 21938646
TI  - Progress on stabilizing and controlling powered upper-limb prostheses.

PMID- 21938644
TI  - Quality of life of patients in renal replacement therapy in Brazil: comparison of
      treatment modalities.
AB  - PURPOSE: This study aimed to analyze and compare the quality of life of renal
      replacement therapy patients undergoing hemodialysis, peritoneal dialysis and
      those with renal transplantation in Brazil. In addition, we aimed to verify
      factors associated with patients' quality of life and the relationship between
      quality of life and treatment modality, socioeconomic and demographic conditions
      as well as aspects related to the disease and health services. METHODS: A
      representative sample of the dialysis units and transplant centers was obtained.
      Structured questionnaires were used to interview 3,036 patients in one of three
      treatment modalities: hemodialysis, peritoneal dialysis and renal transplant.
      Information was collected about socioeconomic and demographic characteristics and
      quality of life measures. RESULTS: There were significant differences between
      renal transplants and both forms of dialysis for all dimensions of the SF-36.
      Hemodialysis patients showed better results in the dimensions of functional
      capacity, physical aspects and social aspects, compared to peritoneal dialysis
      patients. Renal transplant patients had the best mean score in the physical
      component of quality of life. There were no significant differences among
      treatment groups regarding the mental component of quality of life. The physical
      and mental components were associated with comorbidities and age; however, older
      patients had better mental quality of life but worse physical quality of life.
      Patients in a higher socioeconomic class and patients that were not hospitalized
      also reported better quality of life. Unmarried and male patients presented
      better physical quality of life. The dialysis units and transplant centers
      influenced the patients' quality of life. CONCLUSIONS: Renal transplant patients
      have the best quality of life of the three treatment modalities. It is necessary
      to increase access to renal transplants.

PMID- 21938647
TI  - Determining delay created by multifunctional prosthesis controllers.

PMID- 21938648
TI  - Rebuttal to McAleer J. Mobility redux: post-World War II prosthetics and
      functional aids for veterans, 1945 to 2010. J Rehabil Res Dev. 2011;48(2):vii
      xvi.

PMID- 21938649
TI  - Two-degree-of-freedom powered prosthetic wrist.
AB  - Prosthetic wrists need to be compact. By minimizing space requirements, a wrist
      unit can be made for people with long residual limbs. This prosthetic wrist uses
      two motors arranged across the arm within the envelope of the hand. The drive is
      transmitted by a differential so that it produces wrist flexion and extension,
      pronation and supination, or a combination of both. As a case study, it was
      controlled by a single-prosthesis user with pattern recognition of the
      myoelectric signals from the forearm. The result is a compact, two-degree-of
      freedom prosthetic wrist that has the potential to improve the functionality of
      any prosthetic hand by creating a hand orientation that more closely matches
      grasp requirements.

PMID- 21938650
TI  - Target Achievement Control Test: evaluating real-time myoelectric pattern
      recognition control of multifunctional upper-limb prostheses.
AB  - Despite high classification accuracies (~95%) of myoelectric control systems
      based on pattern recognition, how well offline measures translate to real-time
      closed-loop control is unclear. Recently, a real-time virtual test analyzed how
      well subjects completed arm motions using a multiple-degree of freedom (DOF)
      classifier. Although this test provided real-time performance metrics, the
      required task was oversimplified: motion speeds were normalized and unintended
      movements were ignored. We included these considerations in a new, more
      challenging virtual test called the Target Achievement Control Test (TAC Test).
      Five subjects with transradial amputation attempted to move a virtual arm into a
      target posture using myoelectric pattern recognition, performing the test with
      various classifier (1- vs 3-DOF) and task complexities (one vs three required
      motions per posture). We found no significant difference in classification
      accuracy between the 1- and 3-DOF classifiers (97.2% +/- 2.0% and 94.1% +/- 3.1%,
      respectively; p = 0.14). Subjects completed 31% fewer trials in significantly
      more time using the 3-DOF classifier and took 3.6 +/- 0.8 times longer to reach a
      three-motion posture compared with a one-motion posture. These results highlight
      the need for closed-loop performance measures and demonstrate that the TAC Test
      is a useful and more challenging tool to test real-time pattern-recognition
      performance.

PMID- 21938651
TI  - Comparison of electromyography and force as interfaces for prosthetic control.
AB  - The ease with which persons with upper-limb amputations can control their powered
      prostheses is largely determined by the efficacy of the user command interface.
      One needs to understand the abilities of the human operator regarding the
      different available options. Electromyography (EMG) is widely used to control
      powered upper-limb prostheses. It is an indirect estimator of muscle force and
      may be expected to limit the control capabilities of the prosthesis user. This
      study compared EMG control with force control, an interface that is used in
      everyday interactions with the environment. We used both methods to perform a
      position-tracking task. Direct-position control of the wrist provided an upper
      bound for human-operator capabilities. The results demonstrated that an EMG
      control interface is as effective as force control for the position-tracking
      task. We also examined the effects of gain and tracking frequency on EMG control
      to explore the limits of this control interface. We found that information
      transmission rates for myoelectric control were best at higher tracking
      frequencies than at the frequencies previously reported for position control. The
      results may be useful for the design of prostheses and prosthetic controllers.

PMID- 21938652
TI  - Electromyogram pattern recognition for control of powered upper-limb prostheses:
      state of the art and challenges for clinical use.
AB  - Using electromyogram (EMG) signals to control upper-limb prostheses is an
      important clinical option, offering a person with amputation autonomy of control
      by contracting residual muscles. The dexterity with which one may control a
      prosthesis has progressed very little, especially when controlling multiple
      degrees of freedom. Using pattern recognition to discriminate multiple degrees of
      freedom has shown great promise in the research literature, but it has yet to
      transition to a clinically viable option. This article describes the pertinent
      issues and best practices in EMG pattern recognition, identifies the major
      challenges in deploying robust control, and advocates research directions that
      may have an effect in the near future.

PMID- 21938653
TI  - Use of two-axis joystick for control of externally powered shoulder
      disarticulation prostheses.
AB  - We explored a new method for simple and accurate control of shoulder movement for
      externally powered shoulder disarticulation prostheses with a two-axis joystick.
      We tested 10 subjects with intact shoulders and arms to determine the average
      amount of shoulder motion and force available to control an electronic input
      device. We then applied this information to two different input strategies to
      examine their effectiveness: (1) a traditional rocker potentiometer and a pair of
      force-sensing resistors and (2) a two-axis joystick. Three nondisabled subjects
      and two subjects with shoulder disarticulation amputations attempted to control
      an experimental externally powered shoulder using both control strategies. Two
      powered arms were tested, one with powered flexion/extension and humeral rotation
      and one with powered flexion/extension and adduction/abduction. Overwhelmingly,
      the subjects preferred the joystick control, because it was more intuitively
      linked with their shoulder movement. Additionally, two motions (one in each axis)
      could be controlled simultaneously. This pilot study provides valuable insight
      into an effective means of controlling high-level, externally powered prostheses
      with a two-axis joystick.

PMID- 21938654
TI  - Evaluation of shoulder complex motion-based input strategies for endpoint
      prosthetic-limb control using dual-task paradigm.
AB  - This article describes the design and evaluation of two comprehensive strategies
      for endpoint-based control of multiarticulated powered upper-limb prostheses. One
      method uses residual shoulder motion position; the other solely uses myoelectric
      signal pattern classification. Both approaches are calibrated for individual
      users through a short training protocol. The control systems were assessed both
      quantitatively and qualitatively with use of a functional usability protocol
      based on a dual-task paradigm. The results revealed that the residual motion
      based strategy outperformed the myoelectric signal-based scheme, while neither
      strategy appeared to significantly increase the mental burden demanded of the
      users.

PMID- 21938655
TI  - Prosthetic sockets stabilized by alternating areas of tissue compression and
      release.
AB  - A prosthetist makes a conventional socket by wrapping plaster bandage around the
      residual limb and using the resulting shell to create a positive model. After he
      or she modifies the plaster, it is used to create a laminated socket. Such
      sockets are almost perfect cylinders that encapsulate the limb. The bone is
      centered in soft, compressible tissue that must move aside before the bone can
      push against the socket to transmit force or torque to the prosthesis. In a
      compression/release stabilized (CRS) socket, three or more longitudinal
      depressions compress and displace tissue between the socket wall and the bone to
      reduce lost motion when the bone is moved with respect to the socket. Release
      areas between depressions are opened to accommodate displaced tissue. Without
      these openings provided, the CRS socket will not function as intended. Often, the
      release areas of compression are the struts of a carbon-fiber frame, and the
      regions between struts are left open. A frame with openings may be modified by
      the prosthetist adding a thin membrane fully surrounding the limb but allowing
      the membrane and underlying tissue to enter the release openings. The membrane
      may contain electrodes, and it may constitute a roll-on liner that helps suspend
      the prosthesis. We introduce three socket designs: transradial, transfemoral, and
      transhumeral.

PMID- 21938656
TI  - Development and testing of new upper-limb prosthetic devices: research designs
      for usability testing.
AB  - The purposes of this article are to describe usability testing and introduce
      designs and methods of usability testing research as it relates to upper-limb
      prosthetics. This article defines usability, describes usability research,
      discusses research approaches to and designs for usability testing, and
      highlights a variety of methodological considerations, including sampling, sample
      size requirements, and usability metrics. Usability testing is compared with
      other types of study designs used in prosthetic research.

PMID- 21938657
TI  - Using virtual reality environment to facilitate training with advanced upper-limb
      prosthesis.
AB  - Technological advances in upper-limb prosthetic design offer dramatically
      increased possibilities for powered movement. The DEKA Arm system allows users 10
      powered degrees of movement. Learning to control these movements by utilizing a
      set of motions that, in most instances, differ from those used to obtain the
      desired action prior to amputation is a challenge for users. In the Department of
      Veterans Affairs "Study to Optimize the DEKA Arm," we attempted to facilitate
      motor learning by using a virtual reality environment (VRE) program. This VRE
      program allows users to practice controlling an avatar using the controls
      designed to operate the DEKA Arm in the real world. In this article, we provide
      highlights from our experiences implementing VRE in training amputees to use the
      full DEKA Arm. This article discusses the use of VRE in amputee rehabilitation,
      describes the VRE system used with the DEKA Arm, describes VRE training, provides
      qualitative data from a case study of a subject, and provides recommendations for
      future research and implementation of VRE in amputee rehabilitation. Our
      experience has led us to believe that training with VRE is particularly valuable
      for upper-limb amputees who must master a large number of controls and for those
      amputees who need a structured learning environment because of cognitive
      deficits.

PMID- 21938658
TI  - Myoelectric forearm prostheses: state of the art from a user-centered
      perspective.
AB  - User acceptance of myoelectric forearm prostheses is currently low. Awkward
      control, lack of feedback, and difficult training are cited as primary reasons.
      Recently, researchers have focused on exploiting the new possibilities offered by
      advancements in prosthetic technology. Alternatively, researchers could focus on
      prosthesis acceptance by developing functional requirements based on activities
      users are likely to perform. In this article, we describe the process of
      determining such requirements and then the application of these requirements to
      evaluating the state of the art in myoelectric forearm prosthesis research. As
      part of a needs assessment, a workshop was organized involving clinicians
      (representing end users), academics, and engineers. The resulting needs included
      an increased number of functions, lower reaction and execution times, and
      intuitiveness of both control and feedback systems. Reviewing the state of the
      art of research in the main prosthetic subsystems (electromyographic [EMG]
      sensing, control, and feedback) showed that modern research prototypes only
      partly fulfill the requirements. We found that focus should be on validating EMG
      sensing results with patients, improving simultaneous control of wrist movements
      and grasps, deriving optimal parameters for force and position feedback, and
      taking into account the psychophysical aspects of feedback, such as intensity
      perception and spatial acuity.

PMID- 21938660
TI  - Guest editorial: equine-assisted therapy.

PMID- 21938659
TI  - Electromyogram-based neural network control of transhumeral prostheses.
AB  - Upper-limb amputation can cause a great deal of functional impairment for
      patients, particularly for those with amputation at or above the elbow. Our long
      term objective is to improve functional outcomes for patients with amputation by
      integrating a fully implanted electromyographic (EMG) recording system with a
      wireless telemetry system that communicates with the patient's prosthesis. We
      believe that this should generate a scheme that will allow patients to robustly
      control multiple degrees of freedom simultaneously. The goal of this study is to
      evaluate the feasibility of predicting dynamic arm movements (both
      flexion/extension and pronation/supination) based on EMG signals from a set of
      muscles that would likely be intact in patients with transhumeral amputation. We
      recorded movement kinematics and EMG signals from seven muscles during a variety
      of movements with different complexities. Time-delayed artificial neural networks
      were then trained offline to predict the measured arm trajectories based on
      features extracted from the measured EMG signals. We evaluated the relative
      effectiveness of various muscle subsets. Predicted movement trajectories had
      average root-mean-square errors of approximately 15.7 degrees  and 24.9 degrees 
      and average R(2) values of approximately 0.81 and 0.46 for elbow
      flexion/extension and forearm pronation/supination, respectively.

PMID- 21938661
TI  - Response to Koenig et al. Psychological state estimation from physiological
      recordings during robot-assisted gait rehabilitation. J Rehabil Res Dev.
      2011;48(4): 367-86. Available from: http://www.rehab.research.va.gov/
      jour/11/484/pdf/koenig484.pdf.

PMID- 21938662
TI  - Factors related to rapidity of housing placement in Housing and Urban Development
      Department of Veterans Affairs Supportive Housing program of 1990s.
AB  - The Housing and Urban Development-Department of Veterans Affairs Supportive
      Housing (HUD-VASH) program is the largest supported housing program in the
      country for homeless veterans who are seeking rapid entry into permanent
      independent housing. This study examined factors related to how rapidly clients
      were housed in the early years of the program and how long they stayed in the
      program. Mental health, substance abuse, work/income, criminal history, and site
      were examined as predictors of process times. Regression analyses based on 627
      HUD-VASH clients who entered the program between 1992 and 2003 showed that client
      characteristics were not rate-limiting factors for obtaining HUD-VASH housing;
      i.e., clients who had greater substance abuse problems or more extensive criminal
      histories did not take longer to obtain housing. The large differences associated
      with site of entry partly reflected a curvilinear relationship between the
      duration of operation of the HUD-VASH program and process times; i.e., at
      relatively younger and older programs, clients entered housing slightly faster
      than at programs in the middle range. Lastly, HUD-VASH clients whose case
      managers reported good therapeutic alliances stayed in the program longer. These
      findings have implications for the continued expansion of the HUD-VASH program.

PMID- 21938663
TI  - Assessment technique for computer-aided manufactured sockets.
AB  - This article presents an assessment technique for testing the quality of
      prosthetic socket fabrication processes at computer-aided manufacturing
      facilities. The assessment technique is potentially useful to both facilities
      making sockets and companies marketing manufacturing equipment seeking to assess
      and improve product quality. To execute the assessment technique, an evaluator
      fabricates a collection of test models and sockets using the manufacturing suite
      under evaluation, then measures their shapes using scanning equipment. Overall
      socket quality is assessed by comparing socket shapes with electronic file (e
      file) shapes. To characterize carving performance, model shapes are compared with
      e-file shapes. To characterize forming performance, socket shapes are compared
      with model shapes. The mean radial error (MRE), which is the average difference
      in radii between the two compared shapes, provides insight into sizing quality.
      Interquartile range (IQR), the range of radial error for the best-matched half of
      the points on the compared socket surfaces, provides insight into regional shape
      quality. The source(s) of socket shape error may be pinpointed by separately
      determining MRE and IQR for carving and forming. The developed assessment
      technique may provide a useful tool to the prosthetics community and industry to
      help identify problems and limitations in computer-aided manufacturing and give
      insight into appropriate modifications to overcome them.

PMID- 21938664
TI  - Dynamic stability training improves standing balance control in neuropathic
      patients with type 2 diabetes.
AB  - Patients with type 2 diabetic neuropathy (DN) are at an increased risk of falls
      due to the decreased accurate proprioceptive feedbacks. Effective balance
      training should treat context-specific instabilities of postural control of
      patients with DN. For this purpose, evaluations and balance training were
      designed with a 3-week baseline with evaluation after 3 weeks, followed by
      training over 3 weeks with reevaluation. We acquired control scores for standing
      balance from the Biodex stability system and fluctuations of the center of
      pressure. We performed repeated measure analysis of variance to test mean
      differences in three sessions of assessments. In addition, we compared mean
      differences of each pair of sessions with the least significant difference test.
      We used the paired t-test to compare the pure effects of trainings. Our
      investigation showed that the results of Biodex stability scores and force
      platform medial-lateral sway measurements improved statistically. Significant
      higher open-eyes median and mean frequency values of postural sway in the medial
      lateral direction indicated that balance training allowed patients to develop
      control over the degree of freedom at the hip joint. In conclusion, training that
      compensates for disordered balance indicated by subclinical constraints with
      respect to the guidance effect of external visual feedback improves standing
      postural control in patients with type 2 DN.

PMID- 21938665
TI  - Using multifractal detrended fluctuation analysis to assess sacral skin blood
      flow oscillations in people with spinal cord injury.
AB  - The purpose of this study was to investigate whether the multifractal detrended
      fluctuation analysis (MDFA) of skin blood flow oscillations (BFO) differed
      between nondisabled controls and people with spinal cord injury (SCI). The study
      of skin BFO has shown promise for assessing blood flow control mechanisms and
      risk for pressure ulcers. We recruited 23 subjects, including 11 people with SCI
      and 12 nondisabled controls. Thermally induced maximal sacral skin BFO were
      measured by laser Doppler flowmetry. MDFA was used to characterize nonlinear
      complexity of metabolic (0.0095 to 0.02 Hz), neurogenic (0.02 to 0.05 Hz), and
      myogenic (0.05 to 0.15 Hz) BFO. We found that maximal vasodilation was
      significantly smaller in people with SCI than in nondisabled controls (p < 0.05).
      MDFA showed that metabolic BFO exhibited less complexity in people with SCI (p <
      0.05), neurogenic BFO exhibited less complexity in people with complete SCI (p <
      0.05), and myogenic BFO did not show significant differences between people with
      SCI and nondisabled controls. This study demonstrated the feasibility of using
      the MDFA to characterize nonlinear complexity of BFO, which is related to
      vasodilatory functions in people with SCI.

PMID- 21938666
TI  - Usability testing of multimodal feedback interface and simulated collision
      avoidance power wheelchair for long-term-care home residents with cognitive
      impairments.
AB  - Many older adults in long-term-care homes have complex physical and cognitive
      impairments and have difficulty propelling manual wheelchairs. Power wheelchair
      use is restricted owing to safety concerns. Power wheelchairs with collision
      avoidance features are being developed to enable safe and independent mobility;
      however, a paucity of information exists on interface features to help users
      navigate away from obstacles. We developed a system combining an interface with
      auditory, visual, and haptic feedback and a simulated collision-avoidance power
      wheelchair. This device allowed the investigator to stop movement of the power
      wheelchair when users approached obstacles and to deliver feedback to help them
      navigate. Five long-term-care home residents with mild or moderate cognitive
      impairments evaluated device usability, which included effectiveness, efficiency,
      and user satisfaction. Each resident used the device for six 1 h sessions.
      Observations, feedback interviews, and outcome questionnaires were completed
      during and after the sessions. We found the device effective in enabling
      residents to achieve basic driving tasks and self-identified indoor mobility
      goals. Furthermore, residents perceived workload to be low and were satisfied
      with the device. Residents also felt that the feedback was useful to help them
      navigate away from obstacles.

PMID- 21938667
TI  - User evaluation of three wheelchair securement systems in large accessible
      transit vehicles.
AB  - Ease of use, comfort, security, and independent use of three types of wheelchair
      securement systems were evaluated in a large accessible transit vehicle by 20
      wheelchair and scooter users. The securement systems included a 4-point tie-down
      system, a prototype autodocking system, and a prototype rear-facing wheelchair
      passenger (RF-WP) system. Study participants took a 15-minute city ride and
      completed a survey. Participants responded positively to the autodocking and RF
      WP systems that were quicker and easier to use and allowed more independent use
      than the 4-point tie-down system (p < 0.001). There was concern regarding the RF
      WP system that rear-facing travel made it more difficult to see upcoming stops
      and was less comfortable than a forward-facing ride and that the system may
      damage wheelchair wheels during use. The majority of participants preferred using
      an autodocking system because it allowed secure and independent forward-facing
      travel. Participants found it undesirable, however, that a wheelchair-mounted
      docking adaptor was needed to use the autodocking system. Study results indicate
      a need for improved securement systems for forward-facing use that do not require
      a wheelchair adaptation and can be easily and independently used by wheelchair
      and scooter users.

PMID- 21938668
TI  - Stance control knee mechanism for lower-limb support in hybrid neuroprosthesis.
AB  - A hydraulic stance control knee mechanism (SCKM) was developed to fully support
      the knee against flexion during stance and allow uninhibited motion during swing
      for individuals with paraplegia using functional neuromuscular stimulation (FNS)
      for gait assistance. The SCKM was optimized for maximum locking torque for body
      weight support and minimum resistance when allowing for free knee motion.
      Ipsilateral and contralateral position and force feedback were used to control
      the SCKM. Through bench and nondisabled testing, the SCKM was shown to be capable
      of supporting up to 70 N-m, require no more than 13% of the torque achievable
      with FNS to facilitate free motion, and responsively and repeatedly unlock under
      an applied flexion knee torque of up to 49 N-m. Preliminary tests of the SCKM
      with an individual with paraplegia demonstrated that it could support the body
      and maintain knee extension during stance without the stimulation of the knee
      extensor muscles. This was achieved without adversely affecting gait, and knee
      stability was comparable to gait assisted by knee extensor stimulation during
      stance.

PMID- 21938669
TI  - Development of surgical protocol for implantation of tracheal prostheses in
      sheep.
AB  - This article documents experiments performed in ewes to design an artificial
      larynx. The artificial larynx is composed of a hollow, porous tube that elongates
      the trachea and is capped with a valve that acts as a laryngeal sphincter.
      Through an industrial collaboration, our team developed a porous biomaterial that
      can be colonized by cervical tissues. This biomaterial has been used in animals
      to replace part of the trachea, but it is meant to eventually substitute for
      laryngeal cartilage. The tracheal prosthesis is a hollow cylindrical tube
      composed of titanium microbeads. We performed a study in large animals to
      establish an optimal surgical protocol for tracheal replacement in humans. The
      study included 11 sheep (n = 11) and compared 5 methods of implantation. We
      successfully established an optimal three-step surgical protocol to make the
      porous-titanium tracheal prosthesis functional: (1) large lumen endoprosthetics,
      (2) colonization by the peripheral tissues, and (3) endoprosthetic
      epithelialization. This study is the first step in developing an artificial
      larynx because it successfully identifies a biomaterial capable of extending the
      trachea to allow it to open at the junction of the upper aerodigestive tracts.

PMID- 21938670
TI  - Determinants of Department of Veterans Affairs hearing aid brand dispensing by
      individual audiologists.
AB  - Department of Veterans Affairs (VA) audiologists were surveyed regarding their
      perceptions and evaluations of hearing aid (HA) brands on seven factors
      previously published in peer-reviewed research as important to the HA brand
      preference decision of audiologists. One of the seven factors formed a distinct
      dimension of brand differentiation based on Contract Pricing (dimension 1). Brand
      perceptions for the other six factors were highly correlated with one another;
      this dimension of correlated perceptions was labeled Propensity to Dispense Based
      on a Gestalt Percept (dimension 2). That is, a direct relation exists between the
      collective perception of HA brand and its likelihood of being dispensed. These
      two dimensions accounted for 93.1% of the variance in the perceived differences
      among the HA brands surveyed. Joint-space mapping was used to model the effect of
      altering perceptions on VA HA brand dispensing. Results indicate that few VA
      audiologists (7.7%) dispense HA brands in majority association with contract
      pricing. Instead, the vast majority (77%) form brand preferences in majority
      association with their individualized perceptions.

PMID- 21938671
TI  - Elliptical exercise improves fatigue ratings and quality of life in patients with
      multiple sclerosis.
AB  - Fatigue, reduced quality of life (QOL), and lower physical activity levels are
      commonly reported in patients with multiple sclerosis (MS). This study evaluated
      the effects of elliptical exercise on fatigue and QOL reports in patients with
      MS. Patients with MS (n = 26) completed the Fatigue Severity Scale (FSS), the
      Modified Fatigue Impact Scale (MFIS), and the Medical Outcomes Study 36-Item
      Short Form Health Survey (SF-36) before and after completing 15 elliptical
      exercise training sessions. Changes in fatigue and QOL were assessed based on any
      changes in the fatigue and SF-36 questionnaires, and correlations between changes
      in each of the scales were made to determine whether a relationship was present
      between the fatigue and QOL measures. Results showed significant improvement in
      FSS, MFIS, and five SF-36 subscales as a result of elliptical exercise. The
      change in FSS correlated with change in two of the SF-36 subscales. Elliptical
      exercise for patients with MS results in significant improvements in both fatigue
      and QOL. These findings indicate that regular elliptical exercise could be a part
      of inpatient and outpatient MS rehabilitation programs.

PMID- 21938673
TI  - Developmental immunolocalization of heat shock protein 70 (HSP70) in epithelial
      cell of rat kidney.
AB  - During renal development the cells in the medulla are exposed to elevated and
      variable interstitial osmolality. Heat shock protein 70 (HSP70) is a major
      molecular chaperone and plays an important role in the protection of cells in the
      renal medulla from high osmolality. The purpose of this study was to establish
      the time of immunolocalization and distribution of HSP70 in developing and adult
      rat kidney. In addition, changes in HSP70 immunolocalization following the
      infusion of furosemide were investigated. In adult animals, the HSP70 was
      expressed in the medullary thin ascending limb of Henle's loop (ATL) and inner
      medullary collecting duct (IMCD). In developing kidney, HSP70 immunoreactivity
      was first detected in the IMCD of the papillary tip on postnatal day 1. From four
      to 14 days of age, HSP70 was detected in the ATL after transformation from thick
      ascending limb, beginning at the papillary tip and ascending to the border
      between the outer and inner medulla. The immunolocalization of HSP70 in both the
      ATL and IMCD gradually increased during two weeks. The gradual increase in HSP70
      was associated with an increase in its mRNA abundance. However, furosemide
      infusion resulted in significantly reduced HSP70 immunolocalization in the IMCD
      and ATL. These data demonstrated that the expression of HSP70 was closely
      correlated with changes in interstitial osmolality during the development of the
      kidney. We suggest that HSP70 protects ATL and IMCD cells in the inner medulla
      from the stress of high osmolality and may be involved in the transformation of
      the ATL of the long loop of Henle during renal development.

PMID- 21938674
TI  - Comprehensive histologic analysis of interstitial lipolysis with the 1444 nm
      wavelength during a 3-month follow-up.
AB  - A number of near-infrared wavelengths have been proposed and studied for laser
      lipolysis, but the histologic evaluation of tissue response to laser lipolysis
      during long-term follow-up has been lacking. A 1444 nm Nd:YAG laser with better
      absorption in both fat and water has recently attracted attention. The present
      study was designed to investigate the comprehensive histopathology of 1444 nm
      Nd:YAG laser-assisted lipolysis at different energy levels during a 3-month
      follow-up. Laser lipolysis was performed on porcine fat tissue in vivo using a
      1444 nm Nd:YAG laser (AccuSculpt(r), Lutronic Corporation, Ilsan, Republic of
      Korea) and the total energies delivered interstitially to 10x10 cm2 areas were
      750 J, 1500 J, 2250 J, 3000 J, 3750 J, 4500 J, and 5250 J. Biopsy samples were
      taken and histologically analyzed immediately after biopsy and at 1, 2, 4, and 12
      weeks postoperatively. With a fluence setting above 3000J/100 cm2, inflammation
      was severe and remained by the 3-month follow-up, resulting in severe scarring of
      the fat tissue. Below this energy level, mild lobular inflammation in the early
      phase biopsy had resolved with no scarring by the 3-month follow-up. No
      histologic changes in the epidermis or dermal connective tissue were present.
      This study suggested that controlling the energy level is important for clinical
      applications of laser lipolysis with no significant complications.

PMID- 21938675
TI  - Nuclear relocation of DGKzeta in cardiomyocytes under conditions of
      ischemia/reperfusion.
AB  - Diacylglycerol (DG) and phosphatidic acid (PA) are generated under various
      conditions, such as ligand stimulation and several stresses. They serve as second
      messengers to respond to pathophysiological conditions. DG kinase (DGK) catalyzes
      DG to produce PA. It is regarded as a regulator of these lipid messengers.
      Previous studies show that DGKzeta, a nuclear isozyme, translocates from the
      nucleus to the cytoplasm in hippocampal neurons under transient ischemia and
      never relocates to the nucleus after reperfusion. This study examined whether a
      similar phenomenon is observed in cardiomyocytes, which represent another type of
      postmitotic, terminally differentiated cell. We performed immunostaining on
      ischemic hearts induced by occlusion of the left anterior descending coronary
      artery and on primary cultured cardiomyocytes under oxygen-glucose deprivation
      (OGD). In the animal model, 10 min ischemia is sufficient to cause DGKzeta to
      disappear from the nucleus in cardiomyocytes. However, DGKzeta is observed again
      in the nucleus at 10 min following reperfusion after 10 min ischemia, which
      contrasts sharply with ischemic hippocampal neurons. Similar results were
      obtained from experiments using primary cultured cardiomyocytes under OGD
      conditions, except that DGKzeta relocates autonomously, if at all, to the
      nucleus, even under continuous OGD conditions. Results suggest that DGKzeta is
      involved in the acute phase of cellular response to ischemic stress in
      cardiomyocytes in a similar, but not identical, manner to that of neurons.

PMID- 21938676
TI  - C4d immunohistochemical staining is a sensitive method to confirm immunoreactant
      deposition in formalin-fixed paraffin-embedded tissue in membranous
      glomerulonephritis.
AB  - Although the diagnosis of membranous glomerulonephritis (MGN) may be suspected on
      routine histology of formalin-fixed paraffin-embedded tissue, fresh-frozen tissue
      must be used to show the immunologic nature of the process by direct
      immunofluorescence (IF). The efficiency of IF or immunoperoxidase (IP) detection
      of IgG and C3 using paraffin sections is controversial. This study was designed
      to evaluate whether glomerular C4d deposition using an IP method in formalin
      fixed paraffin-embedded tissue may be a useful marker for MGN. We showed
      characteristic glomerular, granular basement membrane deposition of C4d in 31
      (100%) cases of idiopathic MGN and in 5 cases (100%) of pure class V membranous
      lupus nephritis, in which we had a positive diagnosis of the lesions for
      conventional IF study. Control cases were negative. Nineteen cases of different
      glomerulopathies, including IgA nephropathy, primary type I membranoproliferative
      glomerulonephritis, focal segmental glomerulosclerosis and minimal change disease
      showed diverse reproducible patterns of C4d deposition, without intrinsic
      background. Our results indicate that staining of formalin-fixed paraffin
      embedded tissue for C4d can be used for confirmation of granular basement
      membrane immunoreactant deposition in cases of MGN. This proved to be a reliable
      method that could potentially obviate the need for rebiopsy in cases with absence
      of glomeruli in renal frozen sections or when other adjunct IF or IP methods on
      paraffin sections are negative. C4d immunostaining, using an IP method, deserves
      a place as an adjunct method in the biopsy diagnosis of MGN.

PMID- 21938677
TI  - Transglutaminase 2 expression is significantly increased in cyclosporine-induced
      gingival overgrowth.
AB  - Cyclosporine A is a potent immunosuppressant used to prevent organ transplant
      rejection and treat various autoimmune diseases. However, cyclosporine A can also
      induce gingival overgrowth, which is characterized by increased extracellular
      matrix due to an altered balance between collagen synthesis and degradation. This
      study proposed to verify whether trans-glutaminase 2, an enzyme thought to be
      responsible for the assembly and remodelling of extracellular matrix, plays any
      role in the pathogenesis of cyclosporine A-induced gingival overgrowth.
      Cyclosporine A-induced gingival overgrowths were collected from 21 liver
      transplant patients and case-controlled with 20 non-hyperplastic gingival
      biopsies from healthy patients who had previous periodontal treatment. In both
      groups, the presence and tissue distribution of transglutaminase 2 were
      determined by immunohistochemistry and analyzed in comparison with the tissue
      morphology and expression of lymphocyte-related antigens (CD3 and CD20) and a
      vessel-related marker (CD34). Transglutaminase 2 expression showed a significant
      increase (2.6-fold) in the stromal component of cyclosporine A-treated patients
      compared with controls (p<0.001), which suggested that transglutaminase 2 had a
      role in the pathogenesis of the disease. Further studies should investigate the
      therapeutic effect of anti-transglutaminase 2 drugs (putrescine or 1,4-diamino
      butane) in these patients.

PMID- 21938678
TI  - Expression of adhesion molecules and mucins in human and rhesus macaque
      gastrointestinal epithelial cells.
AB  - Epithelial junctions and mucins play key roles in the gastrointestinal mucosal
      barrier, and their alterations are associated with numerous diseases, including
      carcinomas. The systematic expression of adhesion molecules and mucins in normal
      and malignant human gastrointestinal cells was investigated in this study. In
      normal human gastrointestinal cells, zonula occludens-1 (ZO-1), alpha-catenin,
      beta-catenin, gamma-catenin and desmoglein-2 (DSG2) were located in the
      cytoplasmic membranes, whereas symplekin stained in the nuclei. ZO-1, the three
      catenins, and DSG2 were observed in the gastric and colorectal carcinomas with
      reduced and heterogeneous expression and with abnormal distribution. Symplekin
      was detected in the nuclei of tumor cells in most tumors but not observed in some
      others. The immunohistochemical results for ZO-1 and symplekin on the tissues
      were consistent with the data for the cultured cells obtained by
      immunocytochemical staining and Western blot analysis. MUC1 was not stained in
      the normal gastrointestinal cells without periodate oxidation, but it was
      strongly labeled in the malignant gastrointestinal cells. MUC2 was detected in
      the normal and malignant gastrointestinal cells without the periodate treatment.
      These findings indicate that alterations in the expression of the epithelial
      junctions and mucins are associated with the malignant transformation of
      gastrointestinal cells. In addition, the gastrointestinal epithelial cells of
      rhesus macaques expressed these adhesion molecules and mucins, as did the human
      cells, suggesting that the rhesus monkey is a suitable experimental animal model
      for research on adhesion molecules and mucins.

PMID- 21938679
TI  - Inhibin beta B: a useful tumor marker in uterine endometrioid adenocarcinomas?
AB  - Inhibins, dimeric peptide hormones composed of an alpha-subunit and one of two
      possible beta-subunits (betaA or betaB), exhibit substantial roles in human
      reproduction and in endocrine-responsive tumours. However, the prognostic
      significance and clinical implications of the inhibin-betaB subunit in uterine
      endometrioid adenocarcinomas is still not defined yet. A series of 227 uterine
      endometrioid adenocarcinomas of a previous well-characterized cohort were re
      evaluated for the expression of the inhibin-betaB subunit and correlated with
      several clinicopathological characteristics and the clinical outcome. In this re
      analysis, the betaB-subunit expression demonstrated a significant association
      with the patients' age and cervical involvement. However, inhibin-betaB did not
      significantly affect the patients survival in this large cohort group. However,
      patients with a higher intensity of betaB-subunit immunolabelling had a slightly
      worse survival expectation, although without any significant association,
      suggesting that this subunit might have a substantial role in the carcinogenesis
      and pathology of endometrioid adenocarcinomas. Thus, the inhibin-betaB subunit
      appears not to be a useful prognostic marker regarding endometrioid
      adenocarcinomas. However, further research is warranted in elucidating the
      possible implications of inhibin-betaB and endometrial carcinogenesis.

PMID- 21938680
TI  - MMP-2 and TIMP-2 in the prostates of male and female mongolian gerbils: effects
      of hormonal manipulation.
AB  - TIMPs in the prostates of male and female gerbils and evaluated the effects of
      testosterone on the expression of these enzymes. Ventral prostates from male
      gerbils that were either intact or had been castrated for 7 or 21 days, along
      with prostates from female gerbils that were either intact or had been treated
      with testosterone for 7 or 21 days, were submitted to histological, stereological
      and immunohistochemical analyses. Stereology of prostatic components showed
      significant alterations of tissue compartments in the ventral male prostate after
      castration, especially after 21 days, with a significant increase in stroma.
      Administration of testosterone led to disorganization in the female prostate,
      with a significant increase in collagen fibers and smooth muscle cells after 21
      days, along with the development of epithelial lesions such as PINs. MMP-2
      increased after 21 days of castration in males; however, the TIMP-2
      immunoreaction for this group was weak or absent. In females, the expression of
      MMP-2 appeared to decrease after 7 days of treatment with testosterone, but after
      21 days, both epithelium and stroma showed a stronger reaction for MMP-2 than the
      controls. The expression of TIMP-2 in the treated females was similar to its
      expression in the castrated males. We conclude that the distribution of MMPs and
      TIMPs in both male and female prostates is altered by androgen manipulation, but
      the mechanism of stromal regulation appears to be distinct between genders
      because both the lack of T in castrated males and the excess levels of T in
      treated females lead to the same effect.

PMID- 21938681
TI  - Alterations of the perivascular dystrophin-dystroglycan complex following brain
      lesions: an immunohistochemical study in rats.
AB  - Dystroglycan is a laminin receptor, which with dystrophins and other components
      forms the dystrophin-dystroglycan complex. It has an important role in the
      formation of gliovascular connections, cerebral vascularisation and blood-brain
      barrier. Dystroglycan consists of two sub-units, alpha and beta. Previous studies
      demonstrated that the beta-dystroglycan immunoreactivity of cerebral vessels
      temporarily disappeared in the area adjacent to the lesion, whereas the vascular
      laminin which is not immunoreactive in the intact brain became detectable. The
      present study extends these investigations over other components of the complex:
      utrophin, alpha1-syntrophin and alpha1-dystrobrevin. The experiments were
      performed on adult rats. The lesions were stab wounds or cryogenic lesions in
      deep ketamine-xylasine narcosis. Following survival periods 2 to 30 days, the
      animals were perfused and floating brain sections were processed for fluorescent
      immunohistochemistry. The alpha1-dystrobrevin, like beta-dystroglycan, vanished
      temporarily around the lesion. The immunoreactivity of utrophin changed in a
      similar way to that of laminin. In intact brains they were confined to the
      entering segments of the vessels and to the circumventricular organs. Following
      lesions their immunoreactivity manifested in the vessels around the lesions.
      However, utrophin followed laminin with a delay: their peaks were about POD
      (postoperative days) 21 and 7, respectively. Only immunoreactivity of alpha1
      syntrophin appeared in the reactive astrocytes, peaking at POD 14. Double
      labeling proved its co-localization with GFAP. Cryogenic lesions had similar
      immunohistochemical effects, but provided more suitable samples for Western blot
      analysis, which proved the altered levels of alpha1-dystrobrevin and alpha1
      syntrophin. The phenomena may help to monitor the post-lesion vascular processes
      and the alterations of the gliovascular connections.

PMID- 21938682
TI  - Potential role of chitinases and chitin-binding proteins in host-microbial
      interactions during the development of intestinal inflammation.
AB  - The small and large intestines contain an abundance of luminal antigens derived
      from food products and enteric microorganisms. The function of intestinal
      epithelial cells is tightly regulated by several factors produced by enteric
      bacteria and the epithelial cells themselves. Epithelial cells actively
      participate in regulating the homeostasis of intestine, and failure of this
      function leads to abnormal and host-microbial interactions resulting in the
      development of intestinal inflammation. Major determinants of host susceptibility
      against luminal commensal bacteria include genes regulating mucosal immune
      responses, intestinal barrier function and microbial defense. Of note, it has
      been postulated that commensal bacterial adhesion and invasion on/into host cells
      may be strongly involved in the pathogenesis of inflammatory bowel disease (IBD).
      During the intestinal inflammation, the composition of the commensal flora is
      altered, with increased population of aggressive and detrimental bacteria and
      decreased populations of protective bacteria. In fact, some pathogenic bacteria,
      including Adherent-Invasive Escherichia coli, Listeria monocytogenes and Vibrio
      cholerae are likely to initiate their adhesion to the host cells by expressing
      accessory molecules such as chitinases and/or chitin-binding proteins on
      themselves. In addition, several inducible molecules (e.g., chitinase 3-like 1,
      CEACAM6) are also induced on the host cells (e.g. epithelial cells, lamina
      proprial macrophages) under inflammatory conditions, and are actively
      participated in the host-microbial interactions. In this review, we will
      summarize and discuss the potential roles of these important molecules during the
      development of acute and chronic inflammatory conditions.

PMID- 21938684
TI  - Novel therapeutic strategies to target RCAS1, which induces apoptosis via
      ectodomain shedding.
AB  - The expression of receptor-binding cancer antigen expressed on SiSo cells (RCAS1)
      is associated with aggressive characteristics and poor overall survival for 15
      different human malignancies. The correlation between RCAS1 expression and
      several clinicopathological variables, including tumor size, clinical stage,
      invasion depth and lymph node metastasis highlights this molecule's clinical
      significance. RCAS1 is a biomarker because: (1) its concentration in serum or
      pleural effusion is significantly higher in cancer patients; (2) its level is
      associated with treatment response; and (3) high RCAS1-valued serum from cancer
      patients inhibits growth of RCAS1 putative receptor-expressing K562 cells. RCAS1
      is secreted by ectodomain shedding and induces apoptosis in peripheral
      lymphocytes and natural killer (NK) cells. Although its putative receptor and
      mechanism of apoptosis induction remain undefined, RCAS1 is believed to help
      tumor cells evade immune surveillance. RCAS1 expression is also related to
      changes in extracellular matrix characteristics, reduction of vimentin-positive
      stromal cells, and increased microvessel density (MVD), all suggesting that RCAS1
      may induce connective tissue remodeling. Further exploration of RCAS1 biological
      function will facilitate development of novel therapeutic strategies that target
      RCAS1.

PMID- 21938683
TI  - Polarity proteins and actin regulatory proteins are unlikely partners that
      regulate cell adhesion in the seminiferous epithelium during spermatogenesis.
AB  - In mammalian testis, spermatogenesis takes place in the seminiferous epithelium
      of the seminiferous tubule, which is composed of a series of cellular events.
      These include: (i) spermatogonial stem cell (SSC) renewal via mitosis and
      differentiation of SSC to spermatogenia, (ii) meiosis, (iii) spermiogenesis, and
      (iv) spermiation. Throughout these events, developing germ cells remain adhered
      to the Sertoli cell in the seminiferous epithelium amidst extensive cellular,
      biochemical, molecular and morphological changes to obtain structural support and
      nourishment. These events are coordinated via signal transduction at the cell
      cell interface through cell junctions, illustrating the significance of cell
      junctions and adhesion in spermatogenesis. Additionally, developing germ cells
      migrate progressively across the seminiferous epithelium from the stem cell
      niche, which is located in the basal compartment near the basement membrane of
      the tunica propria adjacent to the interstitium. Recent studies have shown that
      some apparently unrelated proteins, such as polarity proteins and actin
      regulatory proteins, are in fact working in concert and synergistically to
      coordinate the continuous cyclic changes of adhesion at the Sertoli-Sertoli and
      Sertoli-germ cell interface in the seminiferous epithelium during the epithelial
      cycle of spermatogenesis, such that developing germ cells remain attached to the
      Sertoli cell in the epithelium while they alter in cell shape and migrate across
      the epithelium. In this review, we highlight the physiological significance of
      endocytic vesicle-mediated protein trafficking events under the influence of
      polarity and actin regulatory proteins in conferring cyclic events of cell
      adhesion and de-adhesion. Furthermore, these recent findings have unraveled some
      unexpected molecules to be targeted for male contraceptive development, which are
      also targets of toxicant-induced male reproductive dysfunction.

PMID- 21938685
TI  - Chronic rhinitis: a manifestation of leprosy.
AB  - Leprosy, or Hansen disease, is an infection that affects the mucous membranes of
      the respiratory tract and may manifest with nasal symptoms of chronic rhinitis,
      including nasal congestion, rhinorrhea, and intermittent epistaxis. We present a
      case of a woman diagnosed with leprosy as an incidental finding from a biopsy
      obtained during endoscopic sinus surgery for the management of chronic rhinitis.
      The diagnosis of leprosy should be considered in patients with nasal symptoms and
      presumptive chronic rhinitis who do not respond adequately to standard therapies.

PMID- 21938686
TI  - Intermittently symptomatic tracheal diverticulum: a case of a rare clinical
      phenomenon.
AB  - Tracheal diverticula are rarely encountered, and only a handful of cases have
      been described in the literature. In most of these cases the patient was
      asymptomatic. When symptoms have occurred, they usually had an airway component
      such as cough, dyspnea, and recurrent respiratory infection. Imaging techniques
      particularly computed tomography-are beneficial for diagnosing a tracheal
      diverticulum because bronchoscopy can sometimes miss the point of communication
      with the trachea. We report the case of a 62-year-old woman with a tracheal
      diverticulum that manifested as an intermittent, painful right neck mass with
      associated cough, dysphonia, dysphagia/odynophagia, and an occasional
      strangulation/choking sensation.

PMID- 21938687
TI  - Subacute airway obstruction caused by a suprastomal tracheal granuloma following
      tracheotomy in an adult.
AB  - We report a case of a post-tracheotomy suprastomal granuloma in the early
      postoperative phase that caused subacute airway obstruction in a 28-year-old
      woman. The patient had undergone the tracheotomy during the surgical treatment of
      a submental abscess. During recovery, several capping trials had failed.
      Therefore, direct laryngoscopy was performed on postoperative day 11, and it
      revealed that the airway was being obstructed by a tracheal granuloma. The
      granuloma was managed with a partial resection and corticosteroids. The patient
      was successfully decannulated with no recurrence of the granuloma. To the best of
      our knowledge, airway obstruction secondary to a tracheal granuloma has not been
      previously reported as an early complication of a traditional surgical
      tracheotomy in an adult. In this report, we discuss the presenting features of
      this case and we propose several possible etiologies.

PMID- 21938688
TI  - Clinical improvement after escalation for sublingual immunotherapy (SLIT).
AB  - Sublingual immunotherapy (SLIT) permits rapid antigen escalation with an improved
      safety profile over that of subcutaneous immunotherapy. Outcomes for SLIT in
      terms of the timing of clinical improvement were investigated in a retrospective
      review of patients undergoing SLIT who completed quality of life (QOL) and
      medication-use questionnaires at baseline and immediately after antigen
      escalation was performed. A subset of patients (n = 24) also completed
      maintenance-phase questionnaires. Paired post-escalation data (mean 5.5 weeks; N
      = 38) demonstrated improvement (p< 0.05) in overall QOL scores and in 6 of 14
      symptom domains. Maintenance phase data (n = 24) revealed significant
      improvements in total QOL scores and in 5 symptom domains. A significant
      reduction in nasal steroid use was also demonstrated during the maintenance phase
      of treatment (p < 0.05). Significant improvement is seen immediately post
      escalation in SLIT patients. This improved QOL appears to be maintained, and
      perhaps even increases, during the maintenance phase, with decreased nasal
      steroid use.

PMID- 21938689
TI  - Endoscopic dacryocystorhinostomy appears to impair nasal mucociliary clearance.
AB  - We conducted a prospective study of 50 adults to investigate changes in nasal
      mucociliary clearance following endoscopic intranasal dacryocystorhinostomy
      (DCR). Each operation was performed with the use of a drill to perforate the
      lateral nasal wall in order to reach the lacrimal sac. Each patient's mucociliary
      clearance time (MCT) was determined by the saccharin test on both the operated
      and nonoperated sides; the preoperative times were compared with postoperative
      measurements made 1 and 3 months following DCR. Preoperatively, the mean MCTs
      were 14.48 minutes on the operated side and 14.50 minutes on the nonoperated side
      not a statistically significant difference (p > 0.05). Postoperatively, the
      corresponding MCTs were 25.22 and 14.98 minutes at 1 month and 18.44 and 15.62
      minutes at 3 months. On the operated side, both postoperative MCTs were
      significantly longer than the preoperative value (p < 0.001), while on the
      nonoperated side, neither postoperative MCT was significantly different from the
      preoperative value (p > 0.05). Also, the postoperative MCTs were significantly
      longer on the operated side than on the nonoperated side at both 1 month (p <
      0.001) and 3 months (p < 0.05). Only 1 of the 50 operations was considered to be
      unsuccessful; the reason for this surgical failure was the patient's ongoing
      complaints of chronic postoperative dacryocystitis. We conclude that endoscopic
      DCR disturbs mucociliary clearance. Changes in MCTs may be attributable to injury
      to the nasal mucosa or to the continuous flow of tears through the nasal mucosa.

PMID- 21938690
TI  - Maxillary sinus nonodontogenic myxoma extending into the sphenoid sinus and
      pterygopalatine fossa: case report.
AB  - Myxomas are benign mesenchymal tumors of uncertain etiology. They can arise from
      odontogenic tissue, as well as from the sinonasal tract and from the facial and
      temporal bones, apparently from nonodontogenic mesenchyme. Although
      histologically benign, myxomas are locally invasive. Histopathology demonstrates
      a characteristically hypocellular lesion with loose stellate cells. We describe
      the case of a 48-year-old woman with a nonodontogenic maxillary sinus myxoma that
      invaded the sphenoid sinus and pterygopalatine fossa. We removed the mass via a
      combined endoscopic and gingivobuccal approach. The rarity of a nonodontogenic
      sinonasal myxoma extending into the sphenoid sinus and pterygopalatine fossa is
      the basis for our presentation of this case.

PMID- 21938691
TI  - Alveolar ridge mucosa protection during suspension laryngoscopy in the edentulous
      patient.

PMID- 21938692
TI  - A variant form of bifid inferior turbinate.

PMID- 21938693
TI  - Effectiveness of a nasal saline gel in the treatment of recurrent anterior
      epistaxis in anticoagulated patients.
AB  - We believe that the use of cauterization in patients with anterior epistaxis in
      the absence of acute bleeding should be discouraged because it does not address
      the underlying cause and because it may even worsen the condition by extending
      the degree of mucosal disruption. This is especially true in patients who are
      receiving anticoagulation therapy. Therefore, we conducted a study to determine
      if the use of a nasal saline gel as monotherapy would be an effective alternative
      to invasive measures in treating recurrent epistaxis in anticoagulated patients.
      Our study group consisted of 74 patients-43 men and 31 women (mean age: 64.4 yr)
      who had been seen in our department over an 18-month period and whose bleeding
      had originated in the anterior portion of the nasal vault. Most patients had been
      experiencing epistaxis for at least 6 months. Patients were given the saline
      nasal gel and taught to gently apply it to the mucosa of the anterior nasal vault
      with a cotton-tipped applicator at the first sign of recurrent bleeding. Patients
      were then followed up periodically over the next 3 months. Among the 74 patients,
      69 (93.2%) had experienced a cessation of their epistaxis at 3 months. The
      results of our study suggest that this simple, painless technique has
      considerable value as a treatment option in this cohort of patients.

PMID- 21938694
TI  - Schwannoma of the palatine tonsil.
AB  - Schwannomas can originate in any peripheral, autonomic, or cranial nerve except
      the olfactory and optic nerves. Between 25 and 48% of all schwannomas have been
      reported to arise in the head and neck, with the acoustic nerve being the most
      common site of origin there. Schwannomas of the palatine tonsil are rare; as far
      as we know, only 6 such cases have been previously reported in the literature; 5
      of these 6 occurred in adults and the other in an adolescent. We report a new
      case in a 42-year-old woman, which was diagnosed on the basis of histopathology.

PMID- 21938695
TI  - Healthcare system failure: a planned strategy?

PMID- 21938696
TI  - Tuberculous otitis media.

PMID- 21938697
TI  - Vagal schwannoma.

PMID- 21938698
TI  - Submental intubation to facilitate the management of maxillofacial trauma.

PMID- 21938699
TI  - Hyalinizing trabecular adenoma of the thyroid gland.

PMID- 21938700
TI  - Anticoagulation therapy as a supplement to recanalization for the treatment of
      sigmoid sinus thrombosis: a case report.
AB  - Treatment of sigmoid sinus thrombosis with long-term anticoagulation therapy
      remains controversial. We present the case of a 6-year-old boy with
      intraoperatively confirmed sigmoid sinus thrombosis secondary to acute
      otomastoiditis. Combined-modality treatment-including mastoidectomy, sigmoid
      sinus decompression, and antibiotic and anticoagulation therapy-resulted in a
      complete clinical resolution of the patient's signs and symptoms. However, a 19
      month follow-up with magnetic resonance venography demonstrated that the sigmoid
      sinus thrombosis itself had not resolved. It is clear that occlusion of the
      sigmoid sinus may persist after the completion of surgical and medical therapy
      for sigmoid sinus thrombosis secondary to otomastoiditis. It remains unclear (1)
      whether anticoagulation treatment aids in recanalization of the affected sinus
      and (2) whether patient outcomes are affected if recanalization is achieved.

PMID- 21938701
TI  - Idiopathic acquired ectopic auricular ossification: a case report and review of
      the literature.
AB  - A petrified auricle is a rare condition in which the structure becomes partially
      or completely rigid. It arises as a consequence of calcification or ossification
      of the auricular cartilage. An ossified auricle is much more rare than a
      calcified cartilage, and it can be diagnosed only by histology. To the best of
      our knowledge, only 18 cases of ossification of the auricle have been previously
      reported in the literature. We report a new case of auricular ossification in a
      72-year-old woman who had taken calcium for the previous 8 years. We also review
      the relevant literature.

PMID- 21938702
TI  - Cholesteatoma of the nose and maxillary and ethmoid sinuses: a rare complication
      of palatal surgery.
AB  - A 10-year-old boy presented with a complaint of a left-sided nasal obstruction
      with an associated foul-smelling discharge. Physical examination and anterior
      rhinoscopy revealed that a whitish, friable mass had completely filled the left
      nasal cavity. On computed tomography, a soft-tissue mass was seen filling the
      cavity and extending to the paranasal sinuses with bone erosion. A biopsy of the
      mass suggested that it represented a cholesteatoma. The lesion was removed via
      nasal endoscopy, and histopathology confirmed the diagnosis of a cholesteatoma.
      No recurrence was noted during 6 months of follow-up. Cholesteatoma of the
      paranasal sinuses is a rare entity, as only a few dozen cases have been reported
      in the literature.

PMID- 21938703
TI  - Syndromes after resection of a cervical schwannoma.
AB  - Cervical schwannomas are rare, as fewer than 250 cases have been reported in the
      literature. The preferred method of removing a schwannoma is enucleation.
      Complications of schwannoma excision include Horner syndrome, first-bite
      syndrome, and Pourfour du Petit syndrome. These complications are usually
      transient and in most cases do not require treatment. Pourfour du Petit syndrome,
      which is the converse of Horner syndrome, occurs with stimulation of the
      sympathetic cervical chain. We report a case of cervical schwannoma in a 44-year
      old woman who developed signs suggestive of both Horner syndrome and Pourfour du
      Petit syndrome following excision of the lesion. We discuss the diagnostic
      workup, surgical treatment, and likely sequelae of this pathology.

PMID- 21938704
TI  - Unilateral macroglossia as sole presenting manifestation of internal carotid
      artery dissection.
AB  - A patient presented with acute-onset, painless, unilateral enlargement of the
      tongue. Steroid treatment for angioedema was ineffective, and a biopsy of an
      apparent mass of the tongue base showed normal tissue. Subsequent magnetic
      resonance imaging showed enlargement, enhancement, asymmetric T2 hyperintensity
      of the left half of the tongue, and dissection of the left cervical internal
      carotid artery (ICA) at the skull base. Unilateral enlargement of the tongue due
      to acute neurogenic denervation may be the sole clinical presentation of a
      spontaneous arterial dissection at the skull base. The hypoglossal neuropathy
      resulted from compression by the pseudoaneurysmal ICA dilatation or ischemia from
      interruption of the vasa nervorum.

PMID- 21938705
TI  - Cervical thymic cyst presenting as a possible cystic nodal metastasis of
      papillary carcinoma in a 53-year-old man.
AB  - Cervical thymic cysts are rare embryonic remnants that develop along the course
      of thymic migration in the neck. They usually occur during infancy and childhood,
      and they are extremely rare in adults. We report a case of cervical thymic cyst
      in a 53-year-old man. The patient presented with a small mass of the thyroid
      gland and a cystic mass at the left level II area of the neck. On histopathology,
      the thyroid mass was identified as a papillary carcinoma and the left-sided neck
      mass was diagnosed as a cervical thymic cyst lined with nonkeratinizing,
      flattened squamous epithelium. The cyst wall contained atrophic thymic tissue
      composed of lymphoid cells, epithelial cords, and Hassall corpuscles. Although it
      is rare, cervical thymic cyst should be considered in the differential diagnosis
      of a lateral cystic neck mass in an adult.

PMID- 21938706
TI  - [Chronic thromboembolic pulmonary hypertension (CTEPH)].

PMID- 21938708
TI  - [What is your diagnosis? Alcohol-induced osteonecrosis of the femoral head].

PMID- 21938709
TI  - [Thoughts on the development of insurance neuroses - a comment].

PMID- 21938710
TI  - [Modern risk assessment and stroke prevention in atrial fibrillation].
AB  - Stroke prophylaxis in patients with non-valvular atrial fibrillation is becoming
      an increasingly dynamic field. The new guidelines from the European Society of
      Cardiology (ESC) recommend a stroke- and bleeding risk-assessment in patients
      with non-valvular atrial fibrillation using the CHA2DS2VASc and the HAS-BLED
      scores, respectively. Furthermore, new drugs for stroke prophylaxis such as
      dabigatran, rivaroxaban and apixaban are undergoing approval in Europe and will
      undoubtedly challenge the well-established vitamin K antagonists. Hence, stroke
      prophylaxis is likely to become a much more individualized treatment in the
      future. This review should help to critically weigh the pros and the cons of the
      new therapeutic options.

PMID- 21938711
TI  - [Cerebral arteriovenous malformations: clinical aspects and treatment
      possibilities].
AB  - Cerebral arteriovenous malformations (AVM) are vascular lesions that occur either
      congenitally or arise in early childhood. AVM are characterised by arteriovenous
      shunts through a nidus of coiled and tortuous vascular connections that connect
      feeding arteries to draining veins. Generally, AVM become evident through
      intracranial haemorrhage in patients aged 20-40 years. Especially, in the young
      adult presenting with epileptic seizures or focal neurological deficits AVM needs
      to be considered as an important differential diagnosis. Treatment modalities for
      the occlusion of symptomatic AVM include microneurosurgery, endovascular
      embolisation, or radiosurgery. These can be performed each on its own or in
      combination with the others. Incidentally diagnosed AVM require a thorough and
      individual consideration of treatment indications. This review deals with the
      current recommendations for the treatment of AVM in the adult patient.

PMID- 21938712
TI  - [Is early anterior cruciate ligament reconstruction sensible? Orthopedic
      viewpoint aspects].

PMID- 21938713
TI  - [Opinion/comment from the perspective of a general practitioner].

PMID- 21938714
TI  - [Malaria prevention].

PMID- 21938715
TI  - [Drug-drug interactions with HIV treatments].
AB  - We develop a differential diagnosis and diagnostic approach to a possible drug
      drug interaction between a cART based on boosted atazanavir and newly given
      drugs. History taking should not only encompass prescribed but also over-the
      counter medication. Exchange of information between attending physicians as to
      therapeutic changes, documented side effects and adherence, therapeutic drug
      monitoring of cART and evaluation by pharmacologist in complex situations are the
      diagnostic tools at hand.

PMID- 21938716
TI  - [Not Available].

PMID- 21938717
TI  - [Not Available].

PMID- 21938719
TI  - [Physician art column. Life experiment].

PMID- 21938721
TI  - AMIGO is expressed in multiple brain cell types and may regulate dendritic growth
      and neuronal survival.
AB  - Amphoterin-induced gene and ORF (AMIGO) is a brain-enriched transmembrane
      immunoglobulin (Ig) superfamily protein with six extracellular leucine-rich
      repeats (LRR) and a single immunoglobulin-like (Ig) domain. We report here that
      AMIGO is a glycosylated protein widely expressed in the central nervous system
      (CNS), and can be found in neurons, astrocytes as well as oligodendrocytes. In
      morphologically mature primary neurons, endogenous AMIGO, and transfected full
      length AMIGO (AMIGO-FL) are largely dendritic, while AMIGO with its LRR domain
      deleted (AMIGO-Ig) is predominantly axonal. In line with AMIGO's dendritic
      localization, siRNA-mediated silencing of AMIGO resulted in reduced dendritic
      growth of cortical neurons in culture. SH-SY5Y cells stably over-expressing AMIGO
      are more resistant to apoptosis induced by staurosporine and H(2) O(2) compared
      to vector controls. AMIGO therefore likely plays important roles in dendritic
      outgrowth during development, and could modulate the survival of developing and
      adult neurons.

PMID- 21938722
TI  - The differential regulation of Gap43 gene in the neuronal differentiation of P19
      cells.
AB  - Growth associated protein 43 (Gap43) is a neuron-specific phosphoprotein, which
      plays critical role in axon growth and synapses functions during neurogenesis.
      Here we identified two transcription start sites (TSSs) of the mouse Gap43 gene
      designated as a proximal site at +1, and a distal TSS at -414. RT-qPCR data
      reveal that the transcripts from +1 increase 10-fold on day-1 post-all-trans
      retinoic acid (RA) treatment, reached a peak value at day-4 and gradually
      reduced. By contrast, the distal TSS directs a late, remarkably sharp increase of
      the transcripts from the day-5 on. An intense signal of Gap43 at the neurites and
      neural network is determined by the efficient transcription of the distal
      promoter as shown in Northern blot and RT-qPCR assay. In addition, the targeting
      of p300 in combination with a differential enrichment of Brm to Brg1 change at
      the distal promoter region of the gene is induced under RA treatment. The over
      hundreds of GA rich stretches and the GAGAG elements located between the two TSSs
      may take parts in the differential transcription of the two TSSs of the Gap43.
      Our findings provide the first evidence on the identification and differential
      transcription of the two TSSs of the mouse Gap43 gene, and the preferential
      distribution of their protein products in the specific stages of RA induced P19
      differentiation. These data suggest the efficient transcription of the distal
      promoter of Gap43 is an important mark for the transition of P19 cells from the
      progenitor stage into neuronal differentiation.

PMID- 21938723
TI  - Initiation of BMP2 signaling in domains on the plasma membrane.
AB  - Bone morphogenetic protein 2 (BMP2) is a potent growth factor crucial for cell
      fate determination. It directs the differentiation of mesenchymal stem cells into
      osteoblasts, chondrocytes, adipocytes, and myocytes. Initiation of BMP2 signaling
      pathways occurs at the cell surface through type I and type II serine/threonine
      kinases housed in specific membrane domains such as caveolae enriched in the
      caveolin-1 beta isoform (CAV1beta, caveolae) and clathrin-coated pits (CCPs). In
      order for BMP2 to initiate Smad signaling it must bind to its receptors on the
      plasma membrane resulting in the phosphorylation of the BMP type Ia receptor
      (BMPRIa) followed by activation of Smad signaling. The current model suggests
      that the canonical BMP signaling pathway, Smad, occurs in CCPs. However, several
      recent studies suggested Smad signaling may occur outside of CCPs. Here, we
      determined; (i) The location of BMP2 binding to receptors localized in caveolae,
      CCPs, or outside of these domains using AFM and confocal microscopy. (ii) The
      location of phosphorylation of BMPRIa on the plasma membrane using membrane
      fractionation, and (iii) the effect of down regulation of caveolae on Smad
      signaling. Our data indicate that BMP2 binds with highest force to BMP receptors
      (BMPRs) localized in caveolae. BMPRIa is phosphorylated in caveolae and the
      disruption of caveolae-inhibited Smad signaling in the presence of BMP2. This
      suggests caveolae are necessary for the initiation of Smad signaling. We propose
      an extension of the current model of BMP2 signaling, in which the initiation of
      Smad signaling is mediated by BMPRs in caveolae.

PMID- 21938724
TI  - Imatinib treatment inhibit IL-6, IL-8, NF-KB and AP-1 production and modulate
      intracellular calcium in CML patients.
AB  - Imatinib (IM) is considered the gold standard for chronic myeloid leukemia (CML)
      treatment, although resistance is emerging as a significant problem. The
      proinflammatory cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8) play an
      important role in cell proliferation, survival, and resistance to glucocorticoid
      mediated cell death. Several transcription factors such as NF-KB and AP-1 are
      activated in response to physiopathological increases and modulation of
      intracellular calcium levels. Our previous study demonstrated that lymphocytes
      from CML patients showed dysregulated calcium homeostasis and oxidative stress.
      Alteration in ionized calcium concentration in the cytosol has been implicated in
      the initiation of secretion, contraction, and cell proliferation. In this study,
      we hypothesized that IL-6, IL-8, NF-kB, AP-1, and intracellular calcium may be
      used as selective and prognostic factors to address the follow-up in CML patients
      treated with imatinib. Our results demonstrated a significant down-regulation in
      IL-6 and IL-8 release as well as NF-kB and AP-1 activation in lymphomonocytes
      from Imatinib-treated patients, compared to samples from untreated patients. In
      parallel, IM treatment, in vivo and in vitro, were able to modulate the
      intracellular calcium concentration of peripheral blood mononuclear cells of CML
      patients by acting at the level of InsP(3) receptor in the endoplasmic reticulum
      and at the level of the purinergic receptors on plasma membrane. The results of
      this study show that measurements of NF-kB, AP-1, IL-6, IL-8, and intracellular
      calcium in CML patients treated with Imatinib may give important information to
      the hematologist on diagnostic criteria and are highly predictive in patients
      with newly diagnosed CML.

PMID- 21938725
TI  - Engineered endothelial progenitor cells that overexpress prostacyclin protect
      vascular cells.
AB  - Prostacyclin (PGI2) is a potent vasodilator and important mediator of vascular
      homeostasis; however, its clinical use is limited because of its short (<2-min)
      half-life. Thus, we hypothesize that the use of engineered endothelial progenitor
      cells (EPCs) that constitutively secrete high levels of PGI2 may overcome this
      limitation of PGI2 therapy. A cDNA encoding COX-1-10aa-PGIS, which links human
      cyclooxygenase-1 (COX-1) to prostacyclin synthase (PGIS), was delivered via
      nucleofection into outgrowth EPCs derived from rat bone marrow mononuclear cells.
      PGI2-secreting strains (PGI2-EPCs) were established by continuous subculturing of
      transfected cells under G418 selection. Genomic PCR, RT-PCR, and Western blot
      analyses confirmed the overexpression of COX-1-10aa-PGIS in PGI2-EPCs. PGI2-EPCs
      secreted significantly higher levels of PGI2 in vitro than native EPCs (P < 0.05)
      and showed higher intrinsic angiogenic capability; conditioned medium (CM) from
      PGI2-EPCs promoted better tube formation than CM from native EPCs (P < 0.05).
      Cell- and paracrine-mediated in vitro angiogenesis was attenuated when COX-1-10aa
      PGIS protein expression was knocked down. Whole-cell patch-clamp studies showed
      that 4-aminopyridine-sensitive K(+) current density was increased significantly
      in rat smooth muscle cells (rSMCs) cocultured under hypoxia with PGI2-EPCs (7.50
      +/- 1.59 pA/pF; P < 0.05) compared with rSMCs cocultured with native EPCs (3.99
      +/- 1.26 pA/pF). In conclusion, we successfully created EPC strains that
      overexpress an active novel enzyme resulting in consistent secretion of PGI2.
      PGI2-EPCs showed enhanced intrinsic proangiogenic properties and provided
      favorable paracrine-mediated cellular protections, including promoting in vitro
      angiogenesis of native EPCs and hyperpolarization of SMCs under hypoxia.

PMID- 21938726
TI  - Endurance exercise training increases APPL1 expression and improves insulin
      signaling in the hepatic tissue of diet-induced obese mice, independently of
      weight loss.
AB  - Hepatic insulin resistance is the major contributor to fasting hyperglycemia in
      type 2 diabetes. The protein kinase Akt plays a central role in the suppression
      of gluconeogenesis involving forkhead box O1 (Foxo1) and peroxisome proliferator
      activated receptor gamma co-activator 1 alpha (PGC-1alpha), and in the control of
      glycogen synthesis involving the glycogen synthase kinase beta (GSK3beta) in the
      liver. It has been demonstrated that endosomal adaptor protein APPL1 interacts
      with Akt and blocks the association of Akt with its endogenous inhibitor,
      tribbles-related protein 3 (TRB3), improving the action of insulin in the liver.
      Here, we demonstrated that chronic exercise increased the basal levels and
      insulin-induced Akt serine phosphorylation in the liver of diet-induced obese
      mice. Endurance training was able to increase APPL1 expression and the
      interaction between APPL1 and Akt. Conversely, training reduced both TRB3
      expression and TRB3 and Akt association. The positive effects of exercise on
      insulin action are reinforced by our findings that showed that trained mice
      presented an increase in Foxo1 phosphorylation and Foxo1/PGC-1alpha association,
      which was accompanied by a reduction in gluconeogenic gene expressions (PEPCK and
      G6Pase). Finally, exercised animals demonstrated increased at basal and insulin
      induced GSK3beta phosphorylation levels and glycogen content at 24 h after the
      last session of exercise. Our findings demonstrate that exercise increases
      insulin action, at least in part, through the enhancement of APPL1 and the
      reduction of TRB3 expression in the liver of obese mice, independently of weight
      loss.

PMID- 21938727
TI  - The role of osteocyte apoptosis in cancer chemotherapy-induced bone loss.
AB  - Intensive cancer chemotherapy leads to significant bone loss, the underlying
      mechanism of which remains unclear. The objective of this study was to elucidate
      mechanisms for effect of the commonly used anti-metabolite methotrexate (MTX) on
      osteocytes and on general bone homeostasis. The current study in juvenile rats
      showed that MTX chemotherapy caused a 4.3-fold increase in the number of
      apoptotic osteocytes in tibial metaphysis, which was accompanied by a 1.8-fold
      increase in the number of tartrate-resistant acid phosphatase-positive bone
      resorbing osteoclasts, and a 35% loss of trabecular bone. This was associated
      with an increase in transcription of the osteoclastogenic cytokines IL-6 (10
      fold) and IL-11 (2-fold). Moreover, the metaphyseal bone of MTX-treated animals
      exhibited a 37.6% increase in the total number of osteocytes, along with 4.9-fold
      higher expression of the DMP-1 transcript. In cultured osteocyte-like MLO-Y4
      cells, MTX treatment significantly increased caspase-3-mediated apoptosis, which
      was accompanied by the formation of plasma membrane-born apoptotic bodies and an
      increase in IL-6 (24-fold) and IL-11 (29-fold) mRNA expression. Conditioned media
      derived from MTX-treated MLO-Y4 cells was twice as strong as untreated media in
      its capacity to induce osteoclast formation in primary bone marrow osteoclast
      precursors. Thus, our in vivo and in vitro data suggested that MTX-induced
      apoptosis of osteocytes caused higher recruitment of DMP-1 positive osteocytes
      and increased osteoclast formation, which could contribute towards the loss of
      bone homeostasis in vivo.

PMID- 21938728
TI  - Individual second virial coefficient determination of monomer and oligomers in
      heat-stressed protein samples using size-exclusion chromatography-light
      scattering.
AB  - The objective of this work was to determine the second virial coefficient (B(22))
      of monomer and oligomer protein species in heat-stressed samples individually and
      simultaneously. A high-performance size-exclusion chromatography equipped with a
      flow-mode detector system enabling measurement of light scattering (LS) and
      ultraviolet transmission in the same cell was used to separate and analyze
      different species. The folded/unfolded nature of the protein was analyzed by
      extrinsic fluorescence spectroscopy using 4,4'-Bis(1-anilinonaphthalene 8
      sulfonate). The B(22) of each species was calculated from the concentration and
      LS data as described in an earlier publication. Upon heat exposure, monomer and
      formed oligomers yielded more negative B(22) values, reflecting stronger
      attractive forces as compared with those for the initial monomer. The increased
      attractive forces are attributed to partial unfolding of the protein species, and
      were reflected in the extent of aggregation. On the basis of the B(22) values,
      the monomer appeared to be the most reactive species after heat stress. In
      summary, the presented B(22) determination technique can be used to analyze and
      follow the nature of intermolecular interactions for all present protein species
      (monomer and oligomers) and provide further understanding of the mechanism of
      protein aggregation and growth of aggregates.

PMID- 21938729
TI  - PI3K: a potential therapeutic target for cancer.
AB  - Phosphatidylinositol 3-kinase (PI3K), one member of lipid kinase family, has been
      demonstrated to play a key role in regulating cell proliferation, adhesion,
      survival, and motility. Recent studies indicate that PI3K related signaling
      pathway is one of the most commonly activated pathways in human cancers.
      Accordingly, pharmacological inhibition of key nodes in this signaling cascade
      has been a focus in developmental therapeutics. To date, Inhibitors targeting
      PI3K or nodes in this pathway, AKT and mTOR, are best studied and have reached
      clinical trials. In this review, we will focus on recent progress on
      understanding of PI3Ks signaling pathway and the development of PI3K inhibitors.

PMID- 21938730
TI  - Surface interactions of monoclonal antibodies characterized by quartz crystal
      microbalance with dissipation: impact of hydrophobicity and protein self
      interactions.
AB  - Surface adsorption of two monoclonal antibodies (mAb1 and mAb2), with widely
      different hydrophobicity and self-association behavior in solution, was examined
      by quartz crystal microbalance with dissipation monitoring to understand how
      adsorption and protein self-interactions near the surface are impacted by their
      intrinsic properties. The dependence of mass and viscoelastic properties of the
      adsorbed protein layer on the type of surface, presence of a surfactant, protein
      concentration, and pH were examined. Adsorption was significantly reduced in the
      presence of surfactant for both proteins, but for the more hydrophobic mAb2,
      residual adsorption remained on polystyrene (PS) and Teflon surfaces. Protein
      concentration had little impact on the adsorbed protein mass for silicon dioxide
      surface but had a significant impact for PS and Teflon surfaces. At high protein
      concentrations, an irreversible layer formed first upon which a reversible layer
      builds. Reversible adsorption was significantly greater at higher protein
      concentrations and significantly higher for mAb2, consistent with its higher
      propensity to reversibly self-associate in solution. The viscoelastic properties
      suggest that adsorbed protein layer at high protein concentrations is more
      hydrated. The adsorbed protein layer at lower pH was more hydrated, and possibly
      more unfolded, consistent with the behavior of the antibody in bulk solution.

PMID- 21938731
TI  - Dynamics of contact line motion during the wetting of rough surfaces and
      correlation with topographical surface parameters.
AB  - Dynamics of contact line motion and wettability is essential in many industrial
      applications such as liquid coating, lubrication, printing, painting,
      condensation, etc. However, the wettability of surfaces depends not only on
      liquid-solid chemical properties but also can be strongly affected by surface
      roughness. As a practical application of controlled wettability, we can mention
      the self-cleaning surfaces, protective clothing, microfluidics devices, electro
      wetting, etc. In this article, we experimentally investigate the spreading of
      droplets deposited onto rough surfaces. Anisotropic surfaces were prepared by
      abrasive polishing on the following materials: aluminium alloy AA7064, titanium
      alloy Ti-6Al-4V, steel AISI 8630, copper alloy UNS C17000, machinable glass
      ceramic, and poly-methylmethacrylate. Topographical 2D parameters were calculated
      according to the following standards, defining Geometrical Product Specifications
      (GPS): ISO 4287, ISO 12085, ISO 13565, ISO 12780, and ISO 12181. The influence of
      topographical parameters on wettability and spreading phenomenon has been
      evaluated by statistical covariance analysis. The following parameters have
      strong influence on fluid spreading on rough surfaces: R(mr) is the relative
      material ratio of the roughness profile, T(rc) is the microgeometric material
      ratio, P(mr) is the relative material ratio of the raw profile, K(r) is the mean
      slope of the roughness motifs, RON(t) is the peak to valley roundness deviation,
      and P(sk) is the Skewness of the raw profile. The physical meaning of selected
      parameters is discussed, and K(r) (the mean slope of the roughness motifs) is
      selected as the most important and physically meaningful parameter. It has been
      found that for all tested materials, fluid spreading shows increasing tendency
      when mean slope of the roughness motifs (K(r) ) increases.

PMID- 21938732
TI  - Mechanical and micromorphological evaluation of chlorhexidine-mediated dentin
      remineralization.
AB  - Chlorhexidine (CHX) has been reported to reduce self-degradation of collagen
      fibrils by inhibiting host-derived protease activity in demineralized dentin.
      Theoretically, if the collagen fibril scaffold of demineralized dentin maintains
      its original crosslinkage pattern on treatment with CHX and appropriate
      supplementation with necessary mineral sources, dentin remineralization may occur
      in demineralized lesions. In this study, we provide direct mechanical and
      micromorphological evidence for the ability of CHX to promote remineralization of
      demineralized dentin. Specifically, with respect to demineralized dentin blocks
      treated with different concentrations of CHX (0.02-2%) and stored in simulated
      body fluid, we have observed a significant increase in the elastic modulus of
      dentin treated with relatively high concentrations of CHX (0.2 and 2%) as storage
      time increased, whereas the elastic modulus of the non-CHX treated control group
      decreased. We have also observed a dense mineral deposition along collagen
      fibrils in the dentin group treated with 0.2 and 2% CHX via field emission
      scanning electron microscopy.

PMID- 21938733
TI  - Modeling the point-spread function in helium-ion lithography.
AB  - We present here a hybrid approach to modeling helium-ion lithography that
      combines the power and ease-of-use of the Stopping and Range of Ions in Matter
      (SRIM) software with the results of recent work simulating secondary electron
      (SE) yield in helium-ion microscopy. This approach traces along SRIM-produced
      helium-ion trajectories, generating and simulating trajectories for SEs using a
      Monte Carlo method. We found, both through simulation and experiment, that the
      spatial distribution of energy deposition in a resist as a function of radial
      distance from beam incidence, i.e. the point spread function, is not simply a sum
      of Gauss functions.

PMID- 21938734
TI  - Ninety days of repeated gavage administration of Rhodiola imbricata extract in
      rats.
AB  - Rhodiola imbricata is a high-altitude plant, possesses adaptogenic,
      immunomodulatory, anti-oxidant and cytoprotective activity, and is widely used in
      traditional medicine. The present study was designed to ascertain the safety of
      aqueous extract of R. imbricata root when administered by gavage to rats for 90
      days. Four groups of animals, each consisting of 15 males and 15 females, were
      administered 0, 100, 250 or 500 mg kg(-1) extract, in a single dose per day. The
      experimental rats when administered 100 mg kg(-1) of extract did not show any
      significant change in their body weight gain, organ/body weight ratio, or
      histological, hematological and biochemical variables studied. However, at higher
      doses of 250 and 500 mg kg(-1) extract, an increase in the body weight of rats of
      both the sexes was apparent without any change in their organ/body weight ratio.
      Furthermore, a noteworthy increase in plasma glucose and protein levels was
      recorded at both the higher doses, which were restored to normal after a 2-week
      withdrawal of treatment. Based on the findings of this study, the no observed
      effect level was 100 mg kg(-1) body weight per day of aqueous root extract of R.
      imbricata in rats administered subchronically.

PMID- 21938735
TI  - Therapeutic effects of whole-body devices applying pulsed electromagnetic fields
      (PEMF): a systematic literature review.
AB  - Pulsed electromagnetic fields (PEMF) delivered by whole-body mats are promoted in
      many countries for a wide range of therapeutic applications and for enhanced well
      being. However, neither the therapeutic efficacy nor the potential health hazards
      caused by these mats have been systematically evaluated. We conducted a
      systematic review of trials investigating the therapeutic effects of low
      frequency PEMF devices. We were interested in all health outcomes addressed so
      far in randomized, sham-controlled, double-blind trials. In total, 11 trials were
      identified. They were focused on osteoarthritis of the knee (3 trials) or the
      cervical spine (1), fibromyalgia (1), pain perception (2), skin ulcer healing
      (1), multiple sclerosis-related fatigue (2), or heart rate variability and well
      being (1). The sample sizes of the trials ranged from 12 to 71 individuals. The
      observation period lasted 12 weeks at maximum, and the applied magnetic flux
      densities ranged from 3.4 to 200 uT. In some trials sporadic positive effects on
      health were observed. However, independent confirmation of such singular findings
      was lacking. We conclude that the scientific evidence for therapeutic effects of
      whole-body PEMF devices is insufficient. Acute adverse effects have not been
      reported. However, adverse effects occurring after long-term application have not
      been studied so far. In summary, the therapeutic use of low-frequency whole-body
      PEMF devices cannot be recommended without more scientific evidence from high
      quality, double-blind trials.

PMID- 21938736
TI  - Regional brain axial and radial diffusivity changes during development.
AB  - The developing human brain shows rapid myelination and axonal changes during
      childhood, adolescence, and early adulthood, requiring successive evaluations to
      determine normative values for potential pathological assessment. Fiber
      characteristics can be examined by axial and radial diffusivity procedures, which
      measure water diffusion parallel and perpendicular to axons and show primarily
      axonal status and myelin changes, respectively. Such measures are lacking from
      widespread sites for the developing brain. Diffusion tensor imaging data were
      acquired from 30 healthy subjects (age 17.7 +/- 4.6 years, range 8-24 years, body
      mass index 21.5 +/- 4.5 kg/m(2), 18 males) using a 3.0-Tesla MRI scanner.
      Diffusion tensors were calculated, principal eigenvalues determined, and axial
      and radial diffusivity maps calculated and normalized to a common space. A set of
      regions of interest was outlined from widespread brain areas within rostral,
      thalamic, hypothalamic, cerebellar, and pontine regions, and average diffusivity
      values were calculated using normalized diffusivity maps and these regions of
      interest masks. Age-related changes were assessed with Pearson's correlations,
      and gender differences evaluated with Student's t-tests. Axial and radial
      diffusivity values declined with age in the majority of brain areas, except for
      midhippocampus, where axial diffusivity values correlated positively with age.
      Gender differences emerged within putamen, thalamic, hypothalamic, cerebellar,
      limbic, temporal, and other cortical sites. Documentation of normal axial and
      radial diffusivity values will help assess disease-related tissue changes. Axial
      and radial diffusivities change with age,with fiber structure and organization
      differing between sexes in several brain areas. The findings may underlie gender
      based functional characteristics, and mandate partitioning age- and gender
      related changes during developmental brain pathology evaluation.

PMID- 21938737
TI  - In vivo imaging of nuclear-cytoplasmic deformation and partition during cancer
      cell death due to immune rejection.
AB  - In this report, we investigated the in vivo cell biology of cancer cells during
      immune rejection. The use of nestin-driven green fluorescent protein (ND-GFP)
      transgenic mice as hosts, in which nascent blood vessels express GFP, and
      implanted dual-color mouse mammary tumor 060562 (MMT) cells, in which the
      cytoplasm expresses red fluorescent protein (RFP) and the nuclei express GFP,
      allowed very important novel observations of angiogenesis and subcellular death
      pathways during immune rejection of a tumor. Nascent blood vessels did not form
      in the initially-growing mouse mammary tumor in ND-GFP immunocompetent mice. In
      contrast, in ND-GFP immunodeficient nude mice, numerous GFP-expressing nascent
      blood vessels grew into the tumor. The results suggest that insufficient nascent
      tumor angiogenesis was important in tumor rejection. During immune rejection, the
      cancer cells deformed their cytoplasm and nuclei, which were readily imaged by
      RFP and GFP, respectively. The nuclear membrane of the cancer cells ruptured, and
      chromatin extruded during partition of cytoplasm and nuclei. T lymphocytes
      infiltrated into the initially-growing tumor in the nestin-GFP transgenic
      immunocompetent mice. The cytotoxic role of the sensitized T lymphocytes was
      confirmed in vitro when they were co-cultured with MMT cells. The CD8a-positive
      lymphocytes attached to the cancer cells and caused nuclear condensation,
      deformation, and partition from their cytoplasm, similar to what occurred in
      vivo. The color-coded subcellular fluorescence-imaging model of immune rejection
      of cancer cells can provide a comprehensive system for further testing of immune
      based treatment for cancer.

PMID- 21938738
TI  - Enhancement of cell-cell contact by claudin-4 in renal epithelial Madin-Darby
      canine kidney cells.
AB  - Claudin-4 regulates ion permeability via a paracellular pathway in renal
      epithelial cells, but its other physiological functions have not been examined.
      We found that hyperosmotic stress increases claudin-4 expression in Madin-Darby
      canine kidney cells. Here, we examined whether claudin-4 affects cell motility,
      cell association, and the intracellular distribution of endogenous junctional
      proteins. Doxycycline-inducible expression of claudin-4 did not change endogenous
      levels of claudin-1, claudin-2, claudin-3, occludin, E-cadherin, and ZO-1.
      Claudin-4 overexpression increased cell association and decreased cell migration
      without affecting cell proliferation. Doxycycline did not change cell junctional
      protein levels, cell association or cell migration in mock-transfected cells. The
      insolubility of claudin-1 and -3 in Triton X-100 was increased by claudin-4
      overexpression, but that of claudin-2, occludin, ZO-1, and E-cadherin was
      unchanged. Immunocytochemistry showed that claudin-4 overexpression increases the
      accumulation of claudin-1 and -3 in tight junctions (TJs). Furthermore, claudin-4
      overexpression increased the association of claudin-4 with claudin-1 and -3.
      These results suggest that claudin-4 accumulates claudin-1 and -3 in TJs to
      enhance cell-cell contact in renal tubular epithelial cells.

PMID- 21938739
TI  - Oct-3/4 promotes migration and invasion of glioblastoma cells.
AB  - As a result of increased glioblastoma migration and invasion into normal brain
      parenchyma, treatment of local tumor recurrence following initial treatment in
      glioblastoma patients remains challenging. Recent studies have demonstrated
      increased Oct-3/4 expression, a self-renewal regulator in stem cells, in
      glioblastomas. However, little is known regarding the influence of Oct-3/4 in
      glioblastoma cell invasiveness. The present study established Oct-3/4
      overexpressing glioblastoma cells, which were prepared from human glioblastoma
      patients, to assess migration, invasion, and mRNA expression profiles of
      integrins and matrix metalloproteinases (MMPs). Compared with control cells, Oct
      3/4 expressing-glioblastoma cells exhibited increased migration and invasion in
      wound healing and Matrigel invasion assays. Oct-3/4 overexpression resulted in
      upregulated FAK and c-Src expression, which mediate integrin signals. Vinculin
      accumulated along the leading edges of Oct-3/4 expressing-glioblastoma cells and
      associated with membrane ruffles during cell migration. Oct-3/4 expressing-cells
      exhibited increased MMP-13 mRNA expression and MMP-13 knockdown by shRNA
      suppressed cell invasion into Matrigel and organotypic brain slices. These
      results suggested that Oct-3/4 enhanced degradation of surrounding extracellular
      matrix by increasing MMP-13 expression and altering integrin signaling.
      Therefore, Oct-3/4 might contribute to tumor promoting activity in glioblastomas.

PMID- 21938740
TI  - Stable overexpression of arginase I and ornithine transcarbamylase in HepG2 cells
      improves its ammonia detoxification.
AB  - HepG2 is an immortalized human hepatoma cell line that has been used for research
      into bioartificial liver systems. However, a low level of ammonia detoxification
      is its biggest drawback. In this work, a recombinant HepG2 cell line with stable
      overexpression of human arginase I (hArgI) and human ornithine transcarbamylase
      (hOTC), HepG2/(hArgI + hOTC)4, was developed using a eukaryotic dual gene
      expression vector pBudCE4.1. (1) The hArgI and hOTC enzymatic activity in
      HepG2/(hArgI + hOTC)4 cells were higher than in the control cells. (2) The
      ammonia tolerance capacity of HepG2/(hArgI + hOTC)4 cells was three times that of
      HepG2 cells and 37.5% of that of primary human hepatocytes in cultivation. In the
      experiment of ammonia detoxification, HepG2/(hArgI + hOTC)4 cells produced 3.1
      times more urea (at 180 mM NH(4) Cl) and 3.1 times more glutamine (at 120 mM
      NH(4) Cl and 15 mM glutamate) than HepG2 cells, reaching 63.1% and 36.0% that of
      primary human hepatocytes, respectively. (3) The hArgI and hOTC overexpression
      did not influence the growth of HepG2 cells and also promoted the expression of
      other ammonia detoxification associated proteins including glutamine synthetase
      (GS), arginase II (ArgII), arginosuccinate synthase (ASS) and arginosuccinate
      lyase (ASL) in HepG2 cells. This work illustrates that the modification reported
      here made significant progress in the improvement of HepG2 cell function and the
      HepG2/(hArgI + hOTC)4 cells will provide a better selection for the application
      of bioartificial liver system.

PMID- 21938741
TI  - Stress-specific responses of p21 expression: implication of transcript variant
      p21 alt-a in long-term hypoxia.
AB  - p21 (CDKN1A, Cip1, Waf1) is a cyclin-dependent kinase inhibitor capable of
      causing cell cycle arrest or promoting cell cycle transit as well as acting as a
      regulator of apoptosis. In this study, we analyzed the effects of various
      antemortem conditions on p21 protein level and expression profiles of known p21
      transcript variants in human heart tissue. The selected death cause groups were:
      non-cardiac, hypothermia, acute ischemia, and chronic hypoxia.
      Immunohistochemical staining of p21 in cardiac myocytes could be observed only in
      hypothermia death cases, in which the mRNA expression of the most abundant
      variant, p21V1, also exceeded that in other death cause groups. Cytoplasmic
      localization of p21 protein in vascular smooth muscle cells together with
      substantially increased expression of cardioprotective Pim-1 especially in
      chronic hypoxia, but in acute ischemia and hypothermia as well, indicate change
      of p21 function from cell cycle arrest to promotion of proliferation and cell
      survival in these cases. In chronic hypoxia deaths the expression of variant p21
      alt-a was highly pronounced whereas the expression of variant p21B was low. In
      chronic hypoxia deaths the expression of p53 was substantially higher compared to
      the other groups, being a potential regulator of p21 alt-a expression. In acute
      ischemia deaths increased expression of variant p21B, suggested to be
      proapoptotic in several cell lines, was observed. Our results suggest a role for
      variant p21 alt-a in hypoxia and for variant p21B in acute myocardial ischemia.
      The known cardioprotective aspect of hypothermia might come from an increased p21
      protein level.

PMID- 21938742
TI  - Cellular distribution of Glut-1 and Glut-5 in benign and malignant human prostate
      tissue.
AB  - Over-expression of hexose transporters (Gluts), specifically Glut-1, is a common
      event in human malignancies. In prostate cancer (CaP), however, expression of
      Gluts has been characterized poorly. In this study, expression and distribution
      of Glut-1 and Glut-5 proteins were characterized using immunohistochemistry in 76
      specimens of benign prostate, 10 specimens of high-grade intraepithelial
      neoplasia (HGPIN), and 28 specimens of CaP. In addition, mRNA expression of Glut
      2, Glut-7, Glut-9, and Glut-11 was analyzed in a set of five specimens of benign
      prostate and CaP. In benign prostate, Glut-1 localized to the basal cells and to
      the basolateral membrane of secretory/luminal epithelial cells. Glut-5, however,
      localized to the apical membrane of secretory/luminal epithelial cells. In HGPIN,
      Glut-1 was immunohistochemically undetectable. Glut-5, however, localized to the
      apical membrane of the neoplastic epithelial cells. In CaP, Glut-1 and Glut-5,
      were immunohistochemically undetectable. However, over-expression of GLUT1 was
      observed in some specimens of highly proliferative intraductal CaP. Glut-7, Glut
      9, and Glut-11 mRNAs were detected in benign prostate and CaP, however, only Glut
      11 mRNA was consistently up-regulated in CaP compared to benign prostate. Low
      levels of expression of Glut-1 protein in the majority of CaP could explain, at
      least in part, the limited clinical applicability of positron emission tomography
      using 2-[18F]-fluoro-2-deoxy-D-glucose for imaging CaP. Moreover, expression of
      Glut-5 in HGPIN suggested that fructose could be utilized as potential metabolic
      substrate in HGPIN. Understanding the molecular mechanisms involved in
      regulation/dysregulation of Gluts in CaP could provide insight in the
      understanding of hexose metabolism in CaP.

PMID- 21938743
TI  - Glycosilated nucleolin as marker for human gliomas.
AB  - Nucleolin is a multifunctional DNA and RNA binding protein involved in regulation
      of gene transcription, chromatin remodeling, RNA metabolism, and ribosomal RNA
      synthesis. Nucleolin seems to be over-expressed in highly proliferative cells and
      is involved in many aspect of gene expression: DNA recombination and replication,
      RNA transcription by RNA polymerase I and II, rRNA processing, mRNA
      stabilization, cytokinesis, and apoptosis. Although nucleolin is localized
      predominantly in the nucleolus, it has also been shown to be localized in a
      phosphorylated/glycolsilated form on the cell surface of different cells.
      Numerous articles dealing with surface nucleolin targeting for tumor therapy have
      been recently published. However, at present, no extensive informations are so
      far available for the presence of nucleolin in human gliomas. In the present work
      we investigated on the presence and localization of nucleolin in glioma on glioma
      specimens at different grade of malignancy and on primary glioma cell cultures
      derived by surgical resection, trying to correlate the presence of glycosilated
      membrane nucleolin with the malignancy grade. To this purpose an antibody
      produced by us against gp273 protein, demonstrated to recognized the glycosilated
      surface nucleolin, has been used. The results obtained demonstrate that surface
      nucleolin increase with the malignancy grade thus suggesting that it may
      constitute a histopathological marker for glioma grading and a possible tool for
      targeted therapy.

PMID- 21938744
TI  - Functional interaction between AQP2 and TRPV4 in renal cells.
AB  - We have previously demonstrated that renal cortical collecting duct cells
      (RCCD(1)), responded to hypotonic stress with a rapid activation of regulatory
      volume decrease (RVD) mechanisms. This process requires the presence of the water
      channel AQP2 and calcium influx, opening the question about the molecular
      identity of this calcium entry path. Since the calcium permeable nonselective
      cation channel TRPV4 plays a crucial role in the response to mechanical and
      osmotic perturbations in a wide range of cell types, the aim of this work was to
      test the hypothesis that the increase in intracellular calcium concentration and
      the subsequent rapid RVD, only observed in the presence of AQP2, could be due to
      a specific activation of TRPV4. We evaluated the expression and function of TRPV4
      channels and their contribution to RVD in WT-RCCD(1) (not expressing aquaporins)
      and in AQP2-RCCD(1) (transfected with AQP2) cells. Our results demonstrated that
      both cell lines endogenously express functional TRPV4, however, a large
      activation of the channel by hypotonicity only occurs in cells that express AQP2.
      Blocking of TRPV4 by ruthenium red abolished calcium influx as well as RVD,
      identifying TRPV4 as a necessary component in volume regulation. Even more, this
      process is dependent on the translocation of TRPV4 to the plasma membrane. Our
      data provide evidence of a novel association between TRPV4 and AQP2 that is
      involved in the activation of TRPV4 by hypotonicity and regulation of cellular
      response to the osmotic stress, suggesting that both proteins are assembled in a
      signaling complex that responds to anisosmotic conditions.

PMID- 21938745
TI  - Ferromagnetic versus antiferromagnetic exchange interactions in
      tetrathiafulvalene-based 3d/4f heterobimetallic complexes.
AB  - (TTF-salphen)M compounds (TTF-salphen(2-)=4,5-bis(propylthio)tetrathiafulvalene
      N,N'-phenylenebis(salicylideneimine) dianion; M=Cu(II) and Ni(II)) have been
      treated with Ln(hfac)(3).2H(2)O precursors (hfac(-)=1,1,1,5,5,5
      hexafluoroacetylacetonate anion; Ln=Gd(III), Tb(III), and Dy(III)) to elaborate
      unprecedented 3d/4f TTF-based heterobimetallic complexes of formula [(TTF
      salphen)MLn(hfac)(3)]. All the structures of these compounds have been resolved
      by X-ray diffraction on single crystals. The structures of these complexes are
      formed by a TTF-salphen(2-) ligand coordinated to the 3d metal ions in the inert
      tetradentate N(2)O(2) site. The Ln(hfac)(3) fragment is coordinated to the (TTF
      salphen)M one through the two phenolate bridges. Even if the complexes are
      similar in both Cu(II) and Ni(II) families, the crystal packing is different. In
      the first case, dimers of TTF-salphen(2-) donors constitute the organic network.
      In the other case, a reminiscent organic network is observed with S...S contacts.
      The photophysical properties of [(TTF-salphen)CuDy(hfac)(3)] (3) in chloroform
      solution highlight the redshift of the TTF->salphen charge transfer (400 cm(-1))
      relative to the analogue excitations in (TTF-salphen)Cu, which attest to the
      stability of these structures in solution. Static magnetic measurements have
      allowed us to quantify the ferromagnetic interactions (J=+1.29 cm(-1)) between
      Cu(II) and Gd(III) in the [(TTF-salphen)CuGd(hfac)(3)] complex. Finally, an
      empirical method that consists of the comparisons of the magnetic properties of
      [(TTF-salphen)CuTb(hfac)(3)] with [(TTF-salphen)NiTb(hfac)(3)] and [(TTF
      salphen)CuDy(hfac)(3)] with [(TTF-salphen)NiDy(hfac)(3)] has established that
      ferromagnetic interactions take place between Cu(II) and Tb(III) ions, whereas
      unusual antiferromagnetic interactions have been identified between Cu(II) and
      Dy(III) ions.

PMID- 21938746
TI  - Photoreactive nanoparticles as nanometric building blocks for the generation of
      self-healing hydrogel thin films.
AB  - The use of reversible photo-cross-linkable nanoparticles as nano building blocks
      for the formulation of nanostructured self-healing thin hydrogel films is shown
      for the first time. This strategy for the fabrication of autonomous self-healing
      coatings consisted of various microgels bearing surface cinnamate moieties. The
      nanoparticles were formed by miniemulsion copolymerization, which was followed by
      surface functionalization with the cinnamate groups. These nanoparticles were
      then used to form films by drop-casting, followed by interparticle photo-cross
      linking polymerization through the light-induced forward dimerization reaction of
      the previously incorporated cinnamate groups. The reversibility of this
      macroscopic network formation was also demonstrated by photoinducing the backward
      dimerization reaction and carrying out several cycles of photoinduced cross
      linking and de-cross-linking. The self-healing ability through swelling of these
      films following surface damage was also demonstrated. Finally, the ability of
      these self-healing macroscopic films to incorporate additives of different
      chemical nature before photo-cross-linking was evaluated.

PMID- 21938747
TI  - Structure analysis and photocatalytic properties of spinel zinc gallium
      oxonitrides.
AB  - This report describes a detailed structural, electronic, and catalytic
      characterization of zinc gallium oxonitride photocatalysts with a spinel crystal
      structure. The bandgap decreases to less than 3 eV with increasing nitrogen
      content (<3 wt%) and these photocatalysts are active in visible light (lambda>420
      nm) for the degradation of cresol and rhodamine B. Density functional theory
      calculations show that this bandgap reduction is in part associated with
      hybridization between the dopant N 2p states and Zn 3d orbitals at the top of the
      valence band. X-ray photoelectron measurements indicate that nitrogen is indeed
      interacting with the oxide precursor through the formation of both nitride- and
      oxonitride-type species. The incorporation of nitrogen reduces the uniformity of
      the local structure of the spinel Zn-Ga-O-N (ZGON) species, as reflected in X-ray
      absorption spectra and Raman measurements relative to zinc gallate, which
      suggests the presence of defects. The oxonitrides exhibit faster photocatalytic
      rates of reaction than the oxide precursor. The degradation mechanisms were
      determined to be via the attack by hydroxyl radicals and holes for rhodamine B
      and cresol, respectively. Addition of Pt as a co-catalyst increased the rate of
      photodegradation, a result attributed to better charge separation.

PMID- 21938748
TI  - Nestlike C4-symmetric [Co24] metallamacrocycle sustained by p-tert
      butylsulfonylcalix[4]arene and 1,2,4-triazole.

PMID- 21938749
TI  - Cycloalkane and alicyclic heterocycle complexation by new switchable
      resorcin[4]arene-based container molecules: NMR and ITC binding studies.
AB  - The synthesis and structural characterization of novel, "molecular basket"-type
      bridged cavitands is reported. The resorcin[4]arene-based container molecules
      feature well-defined cavities that bind a wide variety of cycloalkanes and
      alicyclic heterocycles. Association constants (K(a)) of the 1:1 inclusion
      complexes were determined by both (1)H NMR and isothermal titration calorimetry
      (ITC). The obtained K(a) values in mesitylene ranged from 1.7*10(2) M(-1) for
      cycloheptane up to 1.7*10(7) M(-1) for morpholine. Host-guest complexation by the
      molecular baskets is generally driven by dispersion interactions, C-H...pi
      interactions of the guests with the aromatic walls of the cavity, and optimal
      cavity filling. Correlations between NMR-based structural data and binding
      affinities support that the complexed heterocyclic guests undergo additional
      polar C-O...C=O, N-H...pi, and S...pi interactions. The first crystal structure
      of a cavitand-based molecular basket is reported, providing precise information
      on the geometry and volume of the inner cavity in the solid state. Molecular
      dynamic (MD) simulations provided information on the size and conformational
      preorganization of the cavity in the presence of encapsulated guests. The
      strongest binding of heterocyclic guests, engaging in polar interactions with the
      host, was observed at a cavity filling volume of 63 +/- 9%.

PMID- 21938750
TI  - Incremental solvation precedes ion-pair separation in enantiomerization of a
      cyano-stabilized Grignard reagent.

PMID- 21938751
TI  - Selective N-alkylation of amines with alcohols by using non-metal-based acid-base
      cooperative catalysis.

PMID- 21938752
TI  - Palladium-catalyzed amidation of N-tosylhydrazones with isocyanides.

PMID- 21938753
TI  - Novel and effective copper-aluminum propane dehydrogenation catalysts.

PMID- 21938754
TI  - Systematic screen for tyrosine kinase rearrangements identifies a novel C6orf204
      PDGFRB fusion in a patient with recurrent T-ALL and an associated
      myeloproliferative neoplasm.
AB  - Gene fusions involving the catalytic domain of tyrosine kinases (TKs) are found
      in a variety of hematological and solid tumor malignancies. Clinically, TK
      fusions have emerged as prime targets for therapy with small molecule kinase
      inhibitors. Unfortunately, identification of TK fusions has been hampered by
      experimental limitations. Here, we developed version 2.0 of a genomically based
      systematic kinase fusion screen and used it to detect a novel imatinib-sensitive
      C6orf204-PDGFRB fusion in a patient with precursor T lymphoblastic lymphoma (T
      ALL) and an associated myeloproliferative neoplasm with eosinophilia. These data
      validate the ability of this targeted capture-sequencing approach to detect TK
      fusion events in small amounts of DNA extracted directly from patient samples.

PMID- 21938756
TI  - Impulsive personality and the ability to resist immediate reward: an fMRI study
      examining interindividual differences in the neural mechanisms underlying self
      control.
AB  - The ability to resist immediate rewards is crucial for lifetime success and
      individual well-being. Using functional magnetic resonance imaging, we assessed
      the association between trait impulsivity and the neural underpinnings of the
      ability to control immediate reward desiring. Low and high extreme impulsivity
      groups were compared with regard to their behavioral performance and brain
      activation in situations, in which they had to forego immediate rewards with
      varying value to achieve a superordinate long-term goal. We found that highly
      impulsive (HI) individuals, who successfully compensated for their lack in
      behavioral self-control, engaged two complementary brain mechanisms when choosing
      actions in favor of a long-term goal, but at the expense of an immediate reward.
      First, self-controlled decisions led to a general attenuation of reward-related
      activation in the nucleus accumbens, which was accompanied by an increased
      inverse connectivity with the anteroventral prefrontal cortex. Second, HI
      subjects controlled their desire for increasingly valuable, but suboptimal
      rewards through a linear reduction of activation in the ventromedial prefrontal
      cortex (VMPFC). This was achieved by an increased inverse coupling between the
      VMPFC and the ventral striatum. Importantly, the neural mechanisms observed in
      the HI group differed from those in extremely controlled individuals, despite
      similar behavioral performance. Collectively, these results suggest trait
      specific neural mechanisms that allow HI individuals to control their desire for
      immediate reward.

PMID- 21938755
TI  - Increasing the accuracy of electromagnetic inverses using functional area source
      correlation constraints.
AB  - Estimating cortical current distributions from electroencephalographic (EEG) or
      magnetoencephalographic data is a difficult inverse problem whose solution can be
      improved by the addition of priors on the associated neural responses. In the
      context of visual activation studies, we propose a new approach that uses a
      functional area constrained estimator (FACE) to increase the accuracy of the
      reconstructions. It derives the source correlation matrix from a segmentation of
      the cortex into areas defined by retinotopic maps of the visual field or by
      functional localizers obtained independently by fMRI. These areas are computed
      once for each individual subject and the associated estimators can therefore be
      reused for any new study on the same participant. The resulting FACE
      reconstructions emphasize the activity of sources within these areas or enforce
      their intercorrelations. We used realistic Monte-Carlo simulations to demonstrate
      that this approach improved our estimates of a diverse set of source
      configurations. Reconstructions obtained from a real EEG dataset demonstrate that
      our priors improve the localization of the cortical areas involved in horizontal
      disparity processing.

PMID- 21938757
TI  - Evidence for a motor somatotopy in the cerebellar dentate nucleus--an FMRI study
      in humans.
AB  - Previous anatomical studies in monkeys have shown that forelimb motor
      representation is located caudal to hindlimb representation within the dorso
      rostral dentate nucleus. Here we investigate human dentate nucleus motor
      somatotopy by means of ultra-highfield (7 T) functional magnetic brain imaging
      (fMRI). Twenty five young healthy males participated in the study. Simple finger
      and foot movement tasks were performed to identify dentate nucleus motor areas.
      Recently developed normalization procedures for group analyses were used for the
      cerebellar cortex and the cerebellar dentate nucleus. Cortical activations were
      in good accordance with the known somatotopy of the human cerebellar cortex.
      Dentate nucleus activations following motor tasks were found in particular in the
      ipsilateral dorso-rostral nucleus. Activations were also present in other parts
      of the nucleus including the contralateral side, and there was some overlap
      between the body part representations. Within the ipsilateral dorso-rostral
      dentate, finger activations were located caudally compared to foot movement
      related activations in fMRI group analysis. Likewise, the centre of gravity (COG)
      for the finger activation was more caudal than the COG of the foot activation
      across participants. A multivariate analysis of variance (MANOVA) on the x, y,
      and z coordinates of the COG indicated that this difference was significant (P =
      0.043). These results indicate that in humans, the lower and upper limbs are
      arranged rostro-caudally in the dorsal aspect of the dentate nucleus, which is
      consistent with studies in non-human primates.

PMID- 21938758
TI  - Dynamically changing effects of corticosteroids on human hippocampal and
      prefrontal processing.
AB  - Stress has a powerful impact on memory. Corticosteroids, released in response to
      stress, are thought to mediate, at least in part, these effects by affecting
      neuronal plasticity in brain regions involved in memory formation, including the
      hippocampus and prefrontal cortex. Animal studies have delineated aspects of the
      underlying physiological mechanisms, revealing rapid, nongenomic effects
      facilitating synaptic plasticity, followed several hours later by a gene-mediated
      suppression of this plasticity. Here, we tested the hypothesis that
      corticosteroids would also rapidly upregulate and slowly downregulate brain
      regions critical for episodic memory formation in humans. To target rapid and
      slow effects of corticosteroids on neural processing associated with memory
      formation, we investigated 18 young, healthy men who received 20 mg
      hydrocortisone either 30 or 180 min before a memory encoding task in a double
      blind, placebo-controlled, counter-balanced, crossover design. We used functional
      MRI to measure neural responses during these memory encoding sessions, which were
      separated by a month. Results revealed that corticosteroids' slow effects reduced
      both prefrontal and hippocampal responses, while no significant rapid actions of
      corticosteroids were observed. Thereby, this study provides initial evidence for
      dynamically changing corticosteroid effects on brain regions involved in memory
      formation in humans.

PMID- 21938760
TI  - "LiZn(TMP)3", a zincate or a turbo-lithium amide reagent? DOSY NMR spectroscopic
      evidence.

PMID- 21938759
TI  - [(RCN)2PdCl2]-catalyzed E/Z isomerization of alkenes: a non-hydride binuclear
      addition-elimination pathway.

PMID- 21938761
TI  - "Ligand-free" cluster quantized charging in an ionic liquid.

PMID- 21938762
TI  - The best of IPSO 2010.

PMID- 21938764
TI  - Letter to the editor: a call for humility and an end to humankind's disruption of
      evolutionary processes.

PMID- 21938763
TI  - Mathematics intervention for prevention of neurocognitive deficits in childhood
      leukemia.
AB  - BACKGROUND: Despite evidence that CNS treatment is associated with cognitive and
      academic impairment, interventions to prevent or mitigate these problems are
      limited. The purpose was to determine if early intervention can prevent declines
      in mathematics abilities. PROCEDURES: Fifty-seven children with ALL were enrolled
      and randomized to a Mathematics Intervention or Standard Care. Subjects completed
      neurocognitive assessments prior to the intervention, post-intervention, and 1
      year later. Parents received written results and recommendations for use with
      their school. The Mathematics Intervention was based on Multiple Representation
      Theory and delivered individually over 1 year. RESULTS: Thirty-two of 57 subjects
      completed the study and were included in data analyses. These 32 subjects
      completed all neurocognitive assessments and, for those in the Intervention
      Group, 40-50 hours of the Mathematics Intervention. There were no group
      differences on relevant demographic variables; risk stratification; number of
      intrathecal methotrexate injections; or high dose systemic methotrexate.
      Significant improvements in calculation and applied mathematics from Baseline to
      Post-Intervention (P = 0.003 and 0.002, respectively) and in visual working
      memory from Baseline to 1 year Follow-up (P = 0.02) were observed in the
      Intervention but not the Standard Care Group. Results from repeated measures
      ANOVA demonstrated significant between group differences for applied mathematics
      [F(2,29) = 12.47, P < 0.001] and visual working memory [F(2,29) = 5.53, P =
      0.009]. CONCLUSIONS: The Mathematics Intervention improved mathematics abilities
      and visual working memory compared to standard care. Future studies are needed to
      translate the Mathematics Intervention into a "virtual" delivery method more
      readily available to parents and children.

PMID- 21938765
TI  - Pioneering studies on the mechanisms of axonal regeneration.
AB  - While ultimately, focus must be placed on experimentation using adult systems,
      vastly important clues to regeneration can be found in the study of the embryonic
      nervous system. In embryonic systems, axonal regeneration is successful before a
      critical period, and numerous advances have resulted from the study of isolated
      cells and tissues in vitro. Studies over many decades from the laboratory of Paul
      C. Letourneau have probed the cellular and molecular phenomena involved in axon
      outgrowth and guidance in the embryonic central and peripheral nervous system and
      have laid the framework for many current advances in regeneration research.
      Letourneau's pioneering work related to growth cone behavior, guidance, and
      regeneration has resulted in considerable contributions toward our understanding
      not only of cellular mechanisms that underlie axon growth, but also of the
      specific areas of study that require attention to accomplish future
      breakthroughs. The present article summarizes some of the major contributions
      from Paul Letourneau and his team in the area of axonal regeneration.

PMID- 21938766
TI  - Oligomeric alpha-synuclein is toxic in vivo.

PMID- 21938767
TI  - Back to the origin of Parkinson's disease therapy: the use of anti-cholinergic
      drugs to dampen levodopa-induced dyskinesia.

PMID- 21938768
TI  - Can we reverse alpha-synuclein lesions?

PMID- 21938769
TI  - [Use of misoprostol and congenital malformations].

PMID- 21938770
TI  - Changes to parental consent procedures in South Africa: implications for school
      based adolescent sexual health research.

PMID- 21938773
TI  - Data-driven. Statistical analysis could help curb hospitalizations.

PMID- 21938774
TI  - Waiting and watching. Chicago's cautious approach yields rewards.

PMID- 21938775
TI  - A Texas standout. 'It's an icon': medical center is the world's largest.

PMID- 21938776
TI  - Preparing for disaster. Emergency network was in the works for 11 years.

PMID- 21938777
TI  - Aiming for partnership. Complexity of consolidation nearly derails deal.

PMID- 21938778
TI  - Another experiment. Quality incentive pay model under way in Boston.

PMID- 21938779
TI  - Being proactive. Banner tightens belt as Medicaid cuts loom.

PMID- 21938780
TI  - Working together. Despite success, integration has its problems too.

PMID- 21938781
TI  - Broadening its reach. System to integrate city's healthcare facilities.

PMID- 21938782
TI  - A new era. Tampa general stays afloat by going private.

PMID- 21938783
TI  - Breaking the cycle PRHI leading health outcome improvements.

PMID- 21938784
TI  - BRAC revamps system. Changes affect delivery of healthcare by military.

PMID- 21938785
TI  - Hospice care defeats Institute for Healthcare Improvement to take Modern
      Healthcare's Big Impact Tournament crown.

PMID- 21938786
TI  - Greening of healthcare. Location and design of facilities are essential to the
      mission of health.

PMID- 21938787
TI  - Uncertain future. Leaders will need to prepare for the oncoming demands of
      reform.

PMID- 21938789
TI  - Transition period. As reform changes set in, uncertainty and challenges are made
      clear.

PMID- 21938788
TI  - In pursuit of value. Financial strategies need to include greater transparency on
      cost, quality.

PMID- 21938790
TI  - A foundation to build on. Though changes are likely, health reform law fills a
      niche, fulfills promises.

PMID- 21938791
TI  - Mobile-izing healthcare. Wireless technologies will continue to revolutionize the
      industry.

PMID- 21938792
TI  - Plotting a strategy. Piecemeal adoption of new technologies can be an expensive
      mistake.

PMID- 21938793
TI  - Insource for success. Looking within, leveraging economies of scale can cut need
      for outside services.

PMID- 21938794
TI  - R. Parker Allen, MD (March 13, 1919-October 1, 2010).

PMID- 21938870
TI  - Closing of U.S. horse slaughter plants still reverberates: GAO study asks
      Congress to fund inspections or institute permanent ban.

PMID- 21938871
TI  - AVMA determining scope of improper practice.

PMID- 21938872
TI  - [Social determining factors of health (12). Approach to health inequality and
      evaluation of health effects].

PMID- 21938873
TI  - Salmonellosis unchanged, other illnesses decline.

PMID- 21938874
TI  - Veterinarians can become leaders of a pack.

PMID- 21938875
TI  - Iowa specialty clinics come to terms.

PMID- 21938876
TI  - Cardiac resources for pets available online.

PMID- 21938877
TI  - U.S. dental school applicants and enrollees, 2009 entering class.
AB  - Over the past two decades, interest in dentistry in the United States has shown a
      steady period of growth. There were 12,210 individuals who applied to the 2009
      entering class of U.S. dental schools. The number of first-time enrollees was
      4,871, the highest figure since 1990. Men continue to comprise the majority of
      applicants and enrollees; however, the percentages of women continue to increase.
      While the 2009 underrepresented minority applicants comprised 12 percent of both
      the applicant and first-time enrollee pools, the percentage of underrepresented
      minority enrollees of underrepresented minority applicants decreased from 2008.
      Seventy-one percent of enrollees earned a baccalaureate degree in biological
      science or chemistry/physical science. Regardless of major fields of study, the
      percent rates of enrollment generally exceeded 32 percent.

PMID- 21938879
TI  - [Health service research (9). Public health administration and health service
      research].

PMID- 21938878
TI  - Concerns and highlights from the July 1 JAVMA.

PMID- 21938880
TI  - Bringing corporate influence to the fore in veterinary medicine.

PMID- 21938881
TI  - [Public health for scientific analysis of society and health (5). Changes in
      tobacco-related policies in Japan and their effects].

PMID- 21938882
TI  - Silent witnesses: deaf-mutes in Graeco-Roman antiquity.
AB  - This article highlights all known instances of individual deaf-mutes in
      antiquity, with special attention as to how their symptoms were described, which
      effects were emphasized, and in what context the cases were reported. Next, the
      Greek and Latin vocabulary to denote deaf-muteness will be examined. Then
      comparative anthropology, literary sources, papyri, inscriptions, and juridic
      cases are used to describe daily life conditions of deaf-mutes. As a conclusion,
      I suggest that misconceptions about the anatomy of deaf-muteness, combined with
      the focus on rhetoric, might have had an impact on the lives of the deaf-mutes
      and the approach towards these people, at lest in certain social environments.

PMID- 21938883
TI  - Requiring use of electronic services by certain claimant representatives. Final
      rules.
AB  - We are revising our rules to require that claimant representatives use our
      electronic services as they become available on matters for which the
      representatives request direct fee payment. In the future, we will publish a
      notice in the Federal Register when we require representatives who request direct
      fee payment on a matter to use our available electronic services. We are also
      adding the requirement to use our available electronic services on matters for
      which the representative requests direct fee payment as an affirmative duty in
      our representative conduct rules. These revisions reflect the increased use of
      technology in representatives' business practices. We expect that the use of
      electronic services will improve our efficiency by allowing us to manage our
      workloads more effectively. These rules do not require claimants to use our
      available electronic services directly; they only require their representatives
      to use the services on matters for which the representatives request direct fee
      payment.

PMID- 21938884
TI  - Spinal muscular atrophy (SMA).

PMID- 21938885
TI  - TRICARE; Continued Health Care Benefit Program expansion. Final rule.
AB  - This final rule executes the expansion of section 1078a of title 10, United
      States Code (U.S.C). With the recent expansions of Military Health System (MHS)
      coverage, particularly with the Reserve Component (RC) members, some MHS
      beneficiaries would not be eligible to purchase Continued Health Care Benefit
      Program (CHCBP) coverage under certain circumstances that terminate their MHS
      coverage. This provision allows the Secretary to establish CHCBP eligibility for
      any category of MHS beneficiaries who otherwise would lose MHS coverage with no
      continued care eligibility. Although the proposed rule listed each authorized
      category of MHS beneficiary eligible to receive care, on further examination this
      format for the rule appeared cumbersome and perhaps confusing. Thus this final
      rule contains some organizational changes to simplify the rule to enhance
      understanding and make clear that any category including future categories of
      beneficiaries are entitled to purchase this CHCBP coverage. This final rule also
      includes administrative changes providing clarification on eligibility
      notifications and the CHCBP premium rate publication process. It updates the
      previous final rule published in the Federal Register on September 30, 1994.

PMID- 21938886
TI  - TRICARE: unfortunate sequelae from noncovered services in a military treatment
      facility. Final rule.
AB  - The Department of Defense is publishing this final rule to allow coverage for
      otherwise covered services and supplies required in the treatment of
      complications (unfortunate sequelae) resulting from a noncovered incident of
      treatment provided in a Military Treatment Facility (MTF), when the initial
      noncovered service has been authorized by the MTF Commander and the MTF is unable
      to provide the necessary treatment of the complications. This final rule is
      necessary to protect TRICARE beneficiaries from incurring financial hardships due
      to the current regulatory restrictions that prohibit TRICARE coverage of
      treatment of the complications resulting from noncovered procedures, even when
      those procedures were conducted in a Department of Defense facility.

PMID- 21938887
TI  - TRICARE; changes included in the National Defense Authorization Act for Fiscal
      Year 2010; expansion of survivor eligibility under the TRICARE Dental Program.
      Final rule.
AB  - The Department is publishing this final rule to implement the National Defense
      Authorization Act for Fiscal Year 2010 (NDAA for FY10), as amended by the
      National Defense Authorization Act for Fiscal Year 2011 (NDAA for FY11).
      Specifically, that legislation expands the survivor eligibility under the TRICARE
      Dental Program (TDP). The 2011 amendment to the legislation entitles the
      surviving spouse and child(ren) continuation of eligibility for the TDP
      regardless of whether they were previously enrolled in the TDP. Prior enrollment
      in the TDP had been a requirement of the 2010 legislation for both the spouse and
      children. The period of continued eligibility for a spouse will be 3 years
      beginning on the date of the member's death. The legislation entitles a child to
      continuation of eligibility for the TDP for the longer of three years or until
      age 21 (or 23 for most full-time students). Survivors, who meet the new
      eligibility requirements, will obtain TDP eligibility as of the publishing of the
      final rule in the Federal Register. Retroactive payment of premiums or claims
      paid for dental treatment during the time of loss of TDP eligibility will not be
      reimbursed to surviving dependents.

PMID- 21938888
TI  - Medicaid program; recovery audit contractors. Final rule.
AB  - This final rule implements section 6411 of the Patient Protection and Affordable
      Care Act (the Affordable Care Act), and provides guidance to States related to
      Federal/State funding of State start-up, operation and maintenance costs of
      Medicaid Recovery Audit Contractors (Medicaid RACs) and the payment methodology
      for State payments to Medicaid RACs. This rule also directs States to assure that
      adequate appeal processes are in place for providers to dispute adverse
      determinations made by Medicaid RACs. Lastly, the rule directs States to
      coordinate with other contractors and entities auditing Medicaid providers and
      with State and Federal law enforcement agencies.

PMID- 21938889
TI  - The effects of therapeutic instrumental music performance on endurance level,
      self-perceived fatigue level, and self-perceived exertion of inpatients in
      physical rehabilitation.
AB  - The present study investigated the effects of a Neurologic Music Therapy (NMT)
      sensory-motor rehabilitation technique, Therapeutic Instrumental Music
      Performance (TIMP) as compared to Traditional Occupational Therapy (TOT), on
      endurance, self-perceived fatigue, and self-perceived exertion of 35 hospitalized
      patients in physical rehabilitation. The present study attempted to examine
      whether an active musical experience such as TIMP with musical cueing (i.e.,
      rhythmic auditory cueing) during physical exercises influences one's perception
      of pain, fatigue, and exertion. All participants were diagnosed with a neurologic
      disorder or had recently undergone orthopedic surgery. Investigators measured the
      effects of TOT and TIMP during upper extremity exercise of the less affected or
      stronger upper extremity. Results showed no significant difference on endurance
      measures between the 2 treatment conditions (TIMP and TOT). Statistically
      significant differences were found between TIMP and TOT when measuring their
      effects on perceived exertion and perceived fatigue. TIMP resulted in
      significantly less perception of fatigue and exertion levels than TOT. TIMP can
      be used foran effective sensory-motor rehabilitation technique to decrease
      perceived exertion and fatigue level of inpatients in physical rehabilitation.

PMID- 21938890
TI  - Therapeutic chorale for persons with chronic mental illness: a descriptive survey
      of participant experiences.
AB  - The purpose of this survey was to assess the relationship between participation
      in a bilingual therapeutic performance choir and the reported quality of life for
      persons living with a chronic psychiatric illness. The participants were 16
      volunteers who ranged in age from 32-65, had a diagnosis of a major mental
      illness, and were members of an existing choir within a psychiatric outpatient
      department of a large urban general hospital. Participants completed a self
      reported quality of life questionnaire designed by the researcher using Likert
      scales, a check list, and qualitative questions. Results demonstrated that
      aspects of participants' lives that they perceived were most positively affected
      by choir membership included self-esteem, emotional expression, mood alteration,
      coping with stress, comfort level within in the group, and the establishment of a
      regular routine. Implications for the use of choirs as a therapeutic medium and
      limitations of the study were discussed.

PMID- 21938891
TI  - History of music therapy treatment interventions for children with autism.
AB  - The purpose of this paper is to provide a systematic review of the history of
      music therapy research and treatment of children with autism. Understanding such
      history is important in order to improve clinical efficacy and inform future
      research. This paper includes a history of autism diagnosis, reviews strengths
      and limitations of music therapy practice with children with autism from 1940
      2009, and suggests direction for future music therapy research and clinical
      practice with this population. Literature was limited to the English language and
      obtained with the following search terms: autism, autistic, (early) infantile
      autism, child, therapeutic music, musical therapy, and music therapy. Table of
      contents from music therapy journals were searched, and reference lists from
      obtained articles were perused for additional articles. This historical review
      focused primarily on journal articles, however, books and book chapters that
      appeared to hold particular historical significance were also included.

PMID- 21938892
TI  - The effect of background music on the perception of personality and demographics.
AB  - This study seeks to discover stereotypes people may have about different music
      genres and if these stereotypes are projected onto an individual. Also, the study
      investigates if music therapy students are more or less biased than non-music
      majors in this regard. Subjects (N=388) were comprised of student members of the
      American Music Therapy Association (N=182) and students from a college in the
      southeastern United States who were not music majors (N=206). Subjects were asked
      to listen to a recording and complete a short survey. Subjects assigned to the
      control condition heard only a person reading a script. Subjects assigned to one
      of the four experimental conditions heard the same recording mixed with
      background music and ambient crowd noise, intended to simulate a live
      performance. Subjects were asked to rate the person in the recording on
      personality descriptors and predict demographic information in the survey. Many
      of the survey responses were significantly affected by the genre of music. For
      example, it was shown that when in the presence of rap or country music, all
      subjects rated the personality of the person in the recording significantly more
      negative than when in the presence of classical, jazz, or no music. There were no
      significant differences between the groups for any variable or condition when
      comparing survey responses between college students and AMTA student members.

PMID- 21938893
TI  - Personal therapy for undergraduate music therapy students: a survey of AMTA
      program coordinators.
AB  - The primary purpose of this study was to gather information in order to
      understand if and how various modalities of personal therapy are employed with
      undergraduate music therapy students in the United States. AMTA degree program
      coordinators were asked about 3 therapy modalities, in particular: verbal
      therapy, music therapy, and expressive arts therapy (excluding music therapy). It
      was predicted that less than a quarter of the respondents would indicate that
      personal therapy of any modality was required in their undergraduate curricula,
      but that a larger percentage would indicate that it was encouraged. Both
      hypotheses were supported, with just over 14% of the respondents indicating that
      they require some form of personal therapy and 32% indicating that they encourage
      it, with 73% of this latter subgroup encouraging verbal therapy and 46%
      encouraging music therapy. It was further predicted that, when therapy was
      required or encouraged, it was most often provided by an individual who was
      associated with the college/university and that therapy was usually provided in a
      group format. Respondent comments related to these 2 questions revealed
      considerable confusion between experiential exercises and personal therapy,
      leading to dubious validity of some of the numerical data. Qualitative treatment
      of narrative responses illuminated 4 salient issues regarding personal therapy
      for undergraduate music therapy students, as follows: (a) the legal and ethical
      feasibility of making personal therapy a requirement; (b) the cost and
      availability of qualified professionals; (c) the benefits of personal therapy as
      an integral facet of undergraduate music therapy training and education; and (d)
      the appropriateness of personal therapy at the undergraduate level of training.

PMID- 21938894
TI  - [Prevention of tobacco addiction in the Armed Forces].
AB  - The problems of tobacco smoking among servicemen are analyzed from the position
      of their interrelations with the quality of service duties performance. On the
      basis of received data the conclusion is drawn that the servicemen with tobacco
      dependence are characterized by lower level of mental resilience, adjustment
      capacities and are related to lower category of fitness for duty. Based on
      analyzes of the world and own country experience the program of tobacco smoking
      prevention among servicemen is proposed.

PMID- 21938895
TI  - [Telemedicine: opinions of dermatovenerologist and patient].
AB  - The article presents the results of the survey of the dermatovenereologists and
      patients to explore their attitude to the telemedicine consultations. It is found
      that most of the dermatovenereologists have the positive attitude towards
      telemedicine consultations. From the perspective of patients using telemedicine
      technology is likely to breach the protection of personal privacy.

PMID- 21938896
TI  - [Information technology in the management of medical support NATO's force].
AB  - The analysis of various control systems of troops (forces) of NATO's force is
      performed. It is shown that much experience in building automated control systems
      for operational and strategic level as the rear, and medical services. However,
      the experience of wars and military conflicts of the last decade has shown
      convincingly that solutions to complex issues of command and control units, as
      well as their interaction is possible only through an integrated approach-
      automation, not only those who first come into the fight, but the forces and
      means, involved in their welfare. Given direction is implemented in the U.S.
      Army's development of automation, in particular, telemedicine.

PMID- 21938897
TI  - [Status and directions of improving of surveillance subsystem of sanitary
      epidemiological situation in the service of emergency medicine of the Ministry of
      Defense].
AB  - The article provides a description of the composition and tasks of government,
      forces and means of preventive direction of Disaster Medicine Service in
      countering the biological threats. The subsystem of supervision of sanitary
      epidemiological situation, functioning at the central, regional and territorial
      levels is entrusted with the organization and conduct of monitoring activities,
      monitoring, assessment, prediction, prevention and elimination of the adverse
      health and sanitary emergencies. The author suggests the promising areas of
      optimization of the subsystem of supervision of sanitary-epidemiological
      situation.

PMID- 21938898
TI  - [Features of the organization and algorithms of actions of forensic experts in
      emergencies and military conflicts].
AB  - The article deals with the problem of identification of unidentified dead bodies
      in emergency situations with mass casualties. The basic principles of forensic
      identification are regulatory and legal regulation, the types, methods and
      algorithm implementation. Solving of the problem of identification because of its
      great social, moral, ethical and political morality is an important public policy
      issue. It is emphasized the importance of an adequate regulatory framework in
      relation to objects and subjects of the identification and regulation of
      algorithms of actions forensic experts.

PMID- 21938899
TI  - [The effectiveness of intraocular delivery of 5-fluoroquinolones for prophylaxis
      of intraocular infection].
AB  - The authors examined the possibility of the usage of ionic soft contact lenses
      for intraocular delivery of antibiotics for prophylaxis of intraocular infection
      in open combat trauma of the eyes during the stages of medical evacuation to the
      local military conflicts, as well as to the hospital before elective surgery. It
      is proved high efficiency lens, moxifloxacin and levofloxacin saturated to
      prevent inflammatory complications of the eyes.

PMID- 21938900
TI  - [Surgical treatment of simple cysts of the kidney in multiphasic hospital].
AB  - The presented work is based on an analysis of survey results and surgical
      treatment of 418 patients with simple renal cysts during the period from 1995 to
      2010. The volume of the cysts ranged from one to 2500 ml. The average volume of
      the operated cysts was 360.2 +/- 306.7 ml. The abilities of the multiphasic
      hospital, equipping it with the modern diagnostic and medical equipment, the long
      experience of work enabled the authors to develop the algorithm of inspection and
      surgical treatment of the patients with simple renal cysts and to develop
      practical recommendations, presenting them in logical schemes.

PMID- 21938901
TI  - [Epidemiological and environmental specifications of acute tonsillitis (angines)
      in contract servicemen of internal troops of the Russian Interior Ministry].
AB  - The features of disease tonsillitis (angines) in contract servicemen of internal
      troops of the Russian Interior Ministry in the period from 2000 to 2009 were
      studied. The authors calculated trends for long-term dynamics of its troops as
      whole and regional commands. The incidence of quinsy in the period under review
      tended to moderate reduction in the rate of 3.2% per year. The most significant
      increase in incidence is observed in a test in 2001 when there was formation of a
      large compound located in the field. In 2009, the share of sore throats in the
      structure of general morbidity of military personnel on a contract by 4.7%, the
      highest rate recorded in their autumn-winter period, due to the influence of
      "cold" factor.

PMID- 21938902
TI  - [Determining of suitability of military personnel of carrier profile based on an
      assessment of the functional state of the visual analyzer].
AB  - The article analyzes the important qualities of a professional military profile
      of the carrier, methodological support, aimed at evaluation, accounting
      professionally important qualities in the practice of professional psychological
      selection. It is also identified a group of professionally important qualities
      with the most highly predictive efficiency for the appointment of personnel for
      the post of operator activity profile.

PMID- 21938903
TI  - [Methodology of medical and psychological analysis of the causes of the pilot's
      errors].
AB  - On the basis of the terms of the concept of "personal factors" the author
      proposes the methodology for medical and psychological analysis of the causes of
      the pilots' errors. We consider the basic qualities of the pilot: the needs and
      motivations, professional readiness for flight, health status and functional
      capacities, professionally important qualities. The author gives the
      characteristics of the components of the aviation system, which create
      prerequisites for the occurrence of the pilots' errors.

PMID- 21938904
TI  - ["Management put though not widely, but a satisfactory and comfortable..."
      (Addresses GVMU on the historical map of St. Petersburg and Moscow)].
AB  - For the first time identified and described the building, which from 1830 housed
      the central management of military medicine in Russia and USSR: it was able to
      identify 13 addresses and historic buildings in both capitals. All buildings have
      a high conservation status and well-preserved (the exception is only demolished
      housing in the Middle GVMU trade rows). Among the buildings occupied by the
      Medical Department of the War Ministry and the Chief of the military-medical
      department were real masterpieces, kind of architectural symbols of the two
      capitals--the creation of architects Carlo Rossi and Roman Klein. The longest
      period (1950-2004) stayed in control of one of the buildings of the Middle
      Trading Rows (Red Square, 5).

PMID- 21938905
TI  - [Military commissariats of the higher medical school of the country in 1920-s].
AB  - Defining influence on activity of the higher medical school of the country in
      1920-1922 was rendered by military commissariats of the higher medical
      educational institutions led by commissioners under the general control of the
      Management at Narkomprose of RSFSR. Military commissioners had the right of a
      casting vote in board of high schools, carried out ideological control and
      provided performance of a class principle, operated financial questions and
      staffing issues, participated in the organization of educational process. Work of
      medical faculty of Smolensk State University (SSU) similarly was under
      construction. But, thanks to a principle position of professors of the faculty,
      enlistment office's actions often were exposed to the criticism here, and many
      incompetent decisions of Military Commissariat have not been realized. It is
      possible to consider as a unique positive role of a Military Commissariat in SSU
      were the actions undertaken for preservation of faculty at attempts of its
      closing in 1920-1922.

PMID- 21938907
TI  - [Vladimir Leonidovich Sviderskii (on the 80th anniversary of his birthday)].

PMID- 21938908
TI  - [Catalytic characteristics of monoamine oxidase of whitefish Coregonus lavaretus
      ludoga].
AB  - Study of substrate-inhibitory specificity of liver mitochondrial monoamine
      oxidase (MAO) of sexually mature individuals of the whitefish Coregonus lavaretus
      ludoga P. from the Ladoga Lake has revealed distinguished peculiarities of
      catalytical properties of this enzyme. The studied MAO, on one hand, like the
      classical enzyme of homoiothermal animals, is able to deaminate tyramine,
      serotonin, benzylamine, tryptamine, and beta-phenylalanine, but, on the other
      hand, to deaminate histamine, the classic substrate of diamine oxidase. The found
      equal activity and sorptional ability of the enzyme toward six studied substrates
      including histamine, as well as results of the substrate-inhibitory analysis with
      use of specific inhibitors--deprenyl and chlorgilin--indicate homogeneity of the
      enzyme. The detected for the first time among the fish MAO wide substrate
      specificity and an unusually low sensitivity to both studied acetylene inhibitors
      does not allow ascribing unanimously the studied enzyme to the known MAO forms of
      organs and tissues of homoiothermal organisms. Apparently, the revealed enzyme
      form of poikilothermal organism is not the true MAO, but performs a large amine
      oxidase function.

PMID- 21938909
TI  - [Accumulation of sodium and potassium ions in oocytes of the river lamprey
      Lampetra fluviatilis during prespawning period].
AB  - Accumulation of Na+ and K+ ions in oocytes of the river lamprey Lampetra
      fluviatilis and their transport across the plasma membrane is realized by two
      main mechanisms--Na,K-pump and Na,K,Cl-cotransport. At the prespawning period
      from December to May the intracellular Na+ concentration was observed to increase
      from 10 to 25 mM and the K+ concentration--from 28 to 45 mM. Results obtained on
      isolated oocytes with aid of 204Tl radioactive label have shown that
      contributions of the Na,K-pump and Na,K,Cl-cotransport to potassium accumulations
      were close until March. In spring, the total K+ inflow almost doubled owing to
      activation of the Na,K-pump, whereas contribution of Na,K,Cl-cotransport did not
      change. It seems that an increase of the intracellular content of the main
      inorganic cations in oocytes resulted in parallel activation of the Na,K-pump and
      probably of Na/H-exchange. The biological significance of activation of these
      mechanisms of ion transport at the prespawning period might be due to a necessity
      of accumulation of Na+ and K+ ions in concentrations optimal for subsequent
      embryonic development.

PMID- 21938910
TI  - [Effect of total hypothermia on the fatty acid composition of blood phospholipids
      of rats and sousliks and light irradiation on chemical processes in lipid
      extract].
AB  - Effect of hypothermia on the fatty acid composition of rat and souslik blood
      phospholipids is studied. Different reaction of these animals to cooling is
      revealed: in rats no changes were observed in the fatty acid composition of blood
      phospholipids, whereas in the hibernating there were significant changes in the
      content of individual fatty acids (FA). The content of monoenic acids in sousliks
      decreased almost by 50%, while the content of saturated acid (C18) and of
      polyenic acids C18 : 2omega6 and C20 : 4omega6 rose significantly. Such changes
      seem to be the mechanism that promotes maintenance of the organism viability
      under conditions of a decreased level of metabolism, heart rhythm, and body
      temperature and is evolutionarily acquired. At the same time, the observed
      changes in the content of individual FA do not lead to sharp changes in such
      integrative parameters as the total non-saturation of phospholipids, which
      determines liquid properties of chylomicrons and other lipolipoprotein transport
      particles of the souslik blood. There are studied absorption spectra of blood
      lipid extracts of rats and sousliks under effect of light as well as effect of
      light upon the FA composition of lipid extracts of these animals. The FA
      composition of lipid extracts has been established to remain practically
      constant, whereas the character of changes of spectra under action of light
      indicates the presence in the extracts of oxidation-reduction reactions. The
      obtained data allow suggesting that in the lipid extract there occurs cooperation
      both of the phospholipid molecules themselves and of them with other organic
      molecules, which makes it possible for fatty acids to participate in processes of
      transport both of electrons and of protons. This novel role of FA as a
      participant of the electron transfer might probably be extrapolated to chemical
      reactions (processes) occurring inside the membrane.

PMID- 21938911
TI  - [Effect of food deprivation on quantitative and time characteristics of feeding
      of goldfish Carassius auratus in norm and under action of adrenaline].
AB  - There was studied effect of intraperitoneally administered adrenaline (0.14
      mg/kg) on volume and time characteristics of feeding (duration of single,
      grouped, and total nutrition) of goldfish Carassius auratus (L.) previously
      maintained on normal and restricted (for 10 and 15 days) diet. The fish on
      restricted diet demonstrated the biphasic alimentary response to the adrenaline
      administration, similar with that in the normally fed fish: a decrease of volume,
      duration of the grouped and total feeding at the first phase of action of hormone
      and an increase--at the second phase; however, the value of the response at the
      first phase of the hormone action was lower, whereas at the second phase--higher
      than in the fish obtaining a sufficient amount of food prior to the experiment.
      Duration of the single feeding rose in fish of all groups including the control
      one, the maximum increase being observed in the goldfish submitted to food
      deprivation. The glycogen content in hepatopancreas of the normally fed goldfish
      exceeded by the end of the experiment 4.5-6 times that in the food-deprived ones.
      The obtained results confirm suggestion that a decrease of the level of reserve
      substances in the body leads to a decrease of the fish receptivity to the stress
      hormone--adrenaline and, hence, to a change of the value of its effects on the
      food-searching goldfish activity, with preservation of dynamics of the
      parameters.

PMID- 21938912
TI  - [Effect of apomorphine on the wakefulness--sleep cycle of the common frog Rana
      temporaria].
AB  - This work considers effects of introduction into spinal lymphatic sac of dopamine
      agonist--apomorphine-(APO) at doses of 0.1, 1.0, 2.0 and 4.0 mg/kg body weight on
      the common frog wakefulness-sleep cycle (WSC). Usually the frog WSC is
      represented by wakefulness and three types of passive-protective behavior: by
      immobility states of the type of catalepsy, catatonia, and cataplexy that are
      characterized by high thresholds of arousal and by different (corresponding to
      the name) skeletal musculature tones. These immoboloty forms are considered as
      homologues of mammalian stress-reaction, hibernation, and sleep. Low apomorphine
      doses produced in WSC a marked decrease of portion of wakefulness and an increase
      of the immoboloty state of the catalepsy; high doses, on the contrary, initially
      promoted in CNS an increase of wakefulness and the state of catalepsy by
      demonstrating thereby its stressogenic action; after this, in WSC these increased
      the portion of the sleep-like immobility state of the catalepsy type that is
      considered as a functional homologue of sleep of homoiotherms. In spectra of
      electrograms of the flog telencephalon the representation of waves of the delta
      diapason rose. Taking into account that the states of catalepsy and cataplexy in
      frogs are under control of the anterior hypothalamus, it can be suggested that
      manifestations of cataplexy (sleep) in frog are due to the low level of
      dopaminergic activity, whereas manifestations of catalepsy (the homologue of
      stress reaction) are due to the high dopamine content in the anterioi
      hypothalamic structures. Comparative analysis of changes in WSC of amphibians and
      mammals in response to administration of dopamine and its agonists allows
      thinking that the role of the dopaminergic neurotransmitter system in regulation
      of the vertebrate WSC is unanimous: the low level of activity of this system
      facilitates development of sleep (catalepsy), whereas the high level provides
      reaction of arousal and is actively included in the system providing stress
      reaction.

PMID- 21938913
TI  - [Influence of oxidative processes in mitochondria on contractility of the frog
      Rana temporaria heart muscle. Effects of cadmium].
AB  - The inotropic Cd2+ action on frog heart is studied with taking into account its
      toxic effects upon mitochondria. Cd2+ at concentrations of 1, 10, and 20 microM
      is established to decrease dosedependently (21.3, 50.3, and 72.0%, respectively)
      the muscle contraction amplitude; this is explained by its competitive action on
      the potential-controlled Ca2(+)-channels of the L-type (Ca 1.2). In parallel
      experiments on isolated rat heart mitochondria (RHM) it was shown that Cd2+ at
      concentrations of 15 and 25 microM produces swelling of non-energized and
      energized mitochondria in isotonic (with KNO2 and NH4NO3) and hypoosmotic (with
      25 mM CH3COOK) media. Study of oxidative processes in RHM by polarographic method
      has shown 20 microM Cd2+ to disturb activity of respiratory mitochondrial chain.
      The rate of endogenous respiration of isolated mitochondria in the medium with
      Cd2+ in the presence of malate and succinate was approximately 5 times lower than
      in control. In experimental preparations, addition into the medium of DNP
      uncoupler of oxidation and phosphorylation did not cause an increase of the
      oxygen consumption rate. Thus, the obtained data indicate that a decrease in the
      cardiac muscle contractility caused by Cd2+ is due not only to its direct
      blocking action on Ca2(+)-channels, but also is mediated by toxic effect on rat
      heart mitochondria, which was manifested as an increase in ion permeability of
      the inner mitochondrial membrane (IMM), acceleration of the energy-dependent K+
      transport into the matrix of mitochondria, and inhibition of their respiratory
      chain.

PMID- 21938914
TI  - [Effect of change in levels of motor activity and innervation on basic and
      secondary rhythms of rat heart rate and respiration in ontogenesis].
AB  - Changes in the heart basic rhythm, its rhythmical variations on periodograms, and
      level of spontaneos motor activity were studied on offspring of white rats from
      newborn to 3-week age at transition from the state of active wakefulness to
      narcosis as well as under conditions of blockade of M-cholinoreceptors with
      atropine. It is shown that the endogenous rhythmical activity can be regulated
      not only by a change in frequency of basic rhythms, but also by action on all
      parameters and properties of their rhythmical variations and secondary rhythms.
      The changes in power of the heart secondary rhythms exceed considerably the
      frequency oscillations of basic rhythms during blockade of cholinergic
      innervation or a change in the motor activity level that affects both the basic
      rhythm circulation and respiration and their variations--secondary rhythms. The
      atropine blockade of M-cholinoreceptors at the studied ages changes the heart
      beating rhythm within the limits of 10% of bradicardia in newborns to tachycardia
      in the 3-week old animals. At the same time, power of the cardiac rhythm
      secondary oscillations changes several times. These data indicate that the
      cholinergic mechanisms play the key role in formation of the secondary rhythms
      and their correlation with motor activity.

PMID- 21938915
TI  - [The blood glucose content in newborn rats depending on level and pattern of
      spontaneous motor activity].
AB  - Earlier we have shown that administration to newborn rats of the pentose
      phosphate cycle inhibitor hydroquinone leads to a change in intensity and pattern
      of spontaneous periodic motor activity (SPMA) characteristic of early stages of
      development. The most typical was the disappearance of the rest period from the
      near-minute cycle "activity--rest" and the appearance of uninterrupted motor
      activity. In several cases, especially after 10 days of development, there was
      noted an enhancement in the SMPA pattern of the motor activity complexes
      following in the decasecond rhythm. In this study, on the 3-10-day old rats
      maintained under conditions of free behavior there was studied the blood glucose
      content in the animals at various periods of the activity-rest cycle. Apart from
      the SPMA phase, its composition (pattern) characterizing the maturity level and
      functional state of spinal motor centers was taken into account. In the 3, 7 and
      10-day old rats at the rest period, the glucose concentration was established to
      differ depending on the motor activity pattern. In the case of the decasecond
      periodicity, it amounts to 5.7 +/- 0.2, 6.3 +/- +/- 0.3, and 7.7 +/- 0.3 mmol/l,
      while at the minute one--6.1 +/- 0.4, 7.8 +/- 0.3, and 7.8 +/- 0.1 mmol/l. At the
      moment of bursts of motor excitation, the glucose concentration falls to 5.2 +/-
      0.1, 6.1 +/- 0.4, and 7.1 +/- +/- 0.3 mm at the decasecond and to 5.4 +/- 0.5,
      6.7 +/- 0.2, and 7.6 +/- 0.3 mmol/l at the near-minute rhythm (for the 3, 7 and
      10-day old animals, respectively). The results obtained on the 5-day rat pups
      differ qualitatively from those observed in other age groups. Thus, the glucose
      concentration at the rest period amounts to 6.8 +/- 0.2 at the decasecond and to
      6.7 +/- 0.4 mmol/l at the nearminute periodicity. At the period of motor
      excitation accompanied by the presence of the decasecond activity rhythm, the
      glucose concentration falls to the level of 6.0 +/- 0.2 mmol/l by differing
      statistically significantly from the observed one in the rest state. In the case
      of the appearance of the minute rhythm, the glucose concentration amounts to 5.8
      +/- +/- 0.3 mmol/l. The obtained data indicate that reproduction of the minute
      and decasecond rhythms recorded in composition of SPMA is accompanied by a change
      in the blood serum glucose level. The degree of a decrease of its concentration
      correlates with a certain activity rhythm: at the decasecond one the fall is 9,
      13, 3, and 7 %, whereas at the minute rhythm--11, 13, 14, and 2% (for the 3-, 5-,
      7- and 10-day old rats, respectively). In id to be noted that a certain effect on
      the activity pattern is produced by the degree of satiety of the rat pups, the
      gastric emptying being accompanied by an increase in expression of the decasecond
      rhythm and of brief jerks. Besides, there occur the significant seasonal
      oscillations of the blood serum glucose concentration in the newborn rat pups--at
      the summer period it is statistically significantly higher than at the winter
      spring period.

PMID- 21938916
TI  - [The immunomorphologic analysis of innervation of chromaffin paraganglian cells
      of the mammalian arteries and heart].
AB  - Innervation of chromaffin cells of paraganglia of the wall of mammalian large
      arterial vessels and heart (in rat, cat, and human) was studied by
      neuromorphological and immunohistochemical methods. There is established
      similarity in structure of specialized, "basket"-type nerve endings of the
      chromaffin cells (ChC) with pericellular nerve apparatuses of sympathetic and
      parasympathetic autonomic neurons. It is proposed to use immunohistochemical
      reaction for synaptophysin as method of selective detection of ChC of paraganglia
      and adrenal medulla. The conclusion is made that synaptophysin-positive terminals
      (SPPT) found on bodies of ChC and postganglionic neurons represent efferent,
      rather than afferent, synapses formed by myelinated axons of preganglionic
      fibers. It is suggested that ChC of paraganglia alongside with their
      characteristic endocrine function participate in complex mechanisms of
      chemoreceptor regulation of tissue homeostasis of mammalian blood vessels and
      heart.

PMID- 21938917
TI  - [Intracellular pH in hepatocytes of the river lamprey Lampetra fluviatilis L.
      during the period of pre-spawning migration].

PMID- 21938918
TI  - [Factors of working environment and process on non-ferrous metallurgy enterprises
      in Bashkortostan Republic and workers' occupational health].
AB  - The authors studied factors of working environment and process on nonferrous
      metallurgy enterprises in Bashkortostan Republic and evaluated their influence on
      the workers' occupational health over 1997-2009, with consideration of
      occupation, sex, age, length of service, work conditions and characters. The
      article demonstrates that sanitary and hygienic characteristics of occupations
      connected with machinery operation are prone to increased integral evaluation of
      work conditions due to underestimation of actual hardiness and intensity of work.

PMID- 21938919
TI  - [Changes in ageing pace and major immune parameters among individuals with long
      exposure to hydrogen sulfide].
AB  - The authors revealed increase in ageing pace, higher level of pro-inflammatory
      cytokine Interleukin-8 and apoptosis marker (p53 protein) in individuals with
      chronic exposure to gas containing hydrogen sulfide. The immune parameters
      studied could serve as markers of premature ageing in individuals engaged into
      gas extraction.

PMID- 21938920
TI  - [Role of polymorphous genes of xenobiotic biotransformation system in
      pathogenesis of occupational allergic dermatoses].
AB  - Studying genetic polymorphism of xenogiotics biotransformation system genes in
      patients with occupational allergic dermatoses, the authors revealed reliably
      higher percentage of polymorphous variants of CYP 1A1 *2C and EPHX1 A-415G genes,
      if compared with reference population. Combination of 3 polymorphous variants of
      xenobiotics biotransformation system genes (CYP 1A1, CYP3A4, EPHX1, GSTM1 and
      GSTT1) is characterized by earlier development, severe course and unfavorable
      prognosis of occupational skin condition.

PMID- 21938921
TI  - [Specificity of cellular response to various occupational toxicants].
AB  - The article covers study concerning influence of coal rock dust and high fluorine
      concentrations on energy metabolism and oxidation-reduction reactions in blood
      WBC of experimental rats. The authors demonstrated that the cells vary in
      response to long action of coal rock dust and high fluorine concentrations.

PMID- 21938922
TI  - [Hormonal and metabolic disorders in machinery construction workers].
AB  - The article presents study results that demonstrate biochemical and neurohumoral
      disorders in machinery construction workers. The authors defined characteristics
      of changed functional state of adrenocorticotropic and luteotropic regulation,
      that is presented in central and peripheral endocrine system divisions.

PMID- 21938923
TI  - [Preclinical study as a basis for hygienic regulation of benzofuran derivatives].
AB  - Experiments on laboratory animals studied toxic effects of benzofuran derivatives
      obtained during anti-arrythmic drug Amiodarone production. Toxic effects were
      studied for single and subacute intake through intragastric, inhalation and
      epicutaneous routes. Recommendations are given for hygienic regulation of
      Amiodarone and intermediate products of its synthesis in the air of workplace.

PMID- 21938924
TI  - [Improvement of method for detecting volatile fatty acids in air].
AB  - The authors demonstrated possible use of capillary columns to detect volatile
      fatty acids in air. Tenax TA as adsorbent is recommended.

PMID- 21938925
TI  - [Soils contamination with heavy metals in Vladivostok].
AB  - To evaluate soil pollution with toxic chemicals near preschool institutions in
      Vladivostok city, the author used atomic absorption spectrophotometry to study
      levels of Zn, Mn, Fe, Cu, Co, Sr, Pb, Cd and Cs. Soils from reference territories
      (nine settlements in Primorsky region) were taken for comparison. The levels in
      the city soil appeared to be reliably higher (Cu level--2.18 times, Zn level-
      2.61 times, that of Pb--5.15 times, Cd level--2.33 times, Sr level--1.85 times
      and Cs level--1.68 times) than those in the reference territories. Findings are
      that soils near preschool institutions in Vladivostok are significantly
      contaminated with heavy metals.

PMID- 21938926
TI  - [Modeling of kidney collecting ducts function in the cell culture conditions].
AB  - Continuous cell lines originating from the kidney collecting duct represent a
      powerful tool for the modeling of water and ions reabsorbtion processes. Present
      review considers the basic methodical approaches being utilized to study
      vasopressin-induced water transport mechanisms in the cell culture conditions-
      microscopical methods, electrophysiological measurements, various ways of
      evaluation of water flow across the cell monolayer, transfections of native and
      mutant proteins, GFP-technology. The results of the highest significance for the
      understanding of collecting ducts function which were obtained with usage of
      these methods are analyzed in the review.

PMID- 21938927
TI  - [Analysis of glycogen structure in rat hepatocytes using cytochemical and FRET
      methods].
AB  - Using cytochemical and FRET (Forster, Resonance Energy Transfer) methods, the
      glycogen structure in rat hepatocytes was investigated during fasting and at
      different time intervals after per os glucose administration to animals.
      Hepatocytes on slides were stained with fluorescent PAS-reaction. Staining the
      slides with ethidium bromide-SO2 (EtBr-SO2) for 40 min revealed a labile glycogen
      fraction (LE), and the subsequent staining the same samples with auramine-SO2 (Au
      SO2) for 50 min showed a stable glycogen fraction (SF) in the cells. The total
      glycogen content (LF and SF) in the hepatocytes at different stages of refeeding
      was determined by means of cytofluorimetry, and then efficiency of FRET was
      measured in the same cells. Registration of FRET in several areas of the cells
      was carried out on a laser scanning confocal microscope Leica TCS SP5 with
      application of FRET AB (Acceptor Photobleaching) procedure. In this procedure,
      auramine served as a donor (D) and ethidium bromide was an acceptor (A). It was
      shown that the efficiency of FRET varied from 10 to 14 % during refeeding, while
      the glycogen structure had a marked influence on the value of this parameter.
      FRET efficiency was shown to correlate with the ratio A/D in the cells of hungry
      rats and at the early stages after glucose administration to animals, which
      reflected the degree of filling of the external tiers of glycogen molecules of
      glucose residues. At later stages, this correlation was either less pronounced or
      absent. It was found that the FRET efficiency can vary by 3-4 times at the same
      value of A/D. Since the probability of energy transfer from D to A is
      proportional to 1/R6, where R is a distance between D and A, such variations of
      the FRET efficiency indicate that the glycogen molecules possess a labile
      structure in which the chain of glucose residues can deviate from its axis by a
      distance of about half their diameter.

PMID- 21938928
TI  - [Satellite DNA as a phylogenetic marker: case study of three genera of the
      Murinae subfamily].
AB  - Satellite DNA (satDNA) represent tens percent of any of the vertebrate genome.
      Still, a complete set of sat-DNA fragments is not determined for either species.
      It is known that some genus with species-specific modifications possess a satDNA
      characteristic for the genus. So, satDNA was used as a phylogenetic marker in
      some cases when precise satDNA fragment was cloned. We used the probe of the
      whole pericentromeric region and 4 cloned satDNA fragments of Mus musculus in
      order to consider probes value for phylogenesis of 3 Murinae genera. Fluorescent
      in situ hybridization (FISH) revealed similar pattern on metaphase spreads inside
      genus Mus, though some difference was noted. None of the satDNA fragment gave
      signal in the centromeric region on chromosomes from genera Sylvaemus and
      Apodemus. These data are in agreement with those on satDNA fragments in the
      genome determined by dot-blot hybridization: M musculus satDNA fragments are
      absent in the genomes of both remote genera while they are present in the genomes
      of the genera Mus, though in different amounts. SatDNA of each genera should be
      cloned for the phylogenetic purposes.

PMID- 21938929
TI  - [Heterogeneity of epidermal cells in relation to nickel accumulation in Alyssum
      hyperaccumulators].
AB  - Epidermal cells of some plants are able to accumulate heavy metals (Zn, Ni, Cd)
      in high concentrations. We have investigated this ability in plants of the genus
      Alyssum L. differing in tolerance to nickel (Ni). It was found that the
      preferential accumulation of Ni occurred in the epidermis, whereas in other
      tissues the metal was detected at lower concentrations. Also it was found that
      the epidermal cells were characterized by heterogeneity in relation to Ni
      accumulation, the largest amount of metal accumulated in the large epidermal
      cells and in trichomes. It was shown species-specific features of Ni distribution
      in the leaf tissues of Alyssum spp. The reasons of the heterogeneity of epidermal
      cells in relation to Ni accumulation are discussed. We have attempted to resolve
      the contradictions encountered in the literature concerning the distribution and
      accumulation of Ni in the leaf tissues of plants of the genus Alyssum L.

PMID- 21938930
TI  - [Inversion polymorphism in the population of Camptochironomus tentans from
      Kaliningrad city].
AB  - This paper present the map of polytene chromosomes and inversion polymorphism of
      widely distributed Chironomidae species, Camptochironomus tentans, from the most
      western locality of Russia--Kaliningrad city. Chromosomes banding pattern is
      designated according to Beermann, 1955. Only one larva (2.9%) had a standard
      banding pattern, and karyotypes of the rest (97.1%) were polymorphic. We have
      found 2.0 heterozygous inversions per individual, and the frequency of hetero-
      and homozygous inversions, taken together, amounted to 2.2 per individual. 17
      inversion banding patterns and 20 genotypic combinations of these patterns were
      found. It was shown that the most frequent inversions in this population were
      identical to these in European populations.

PMID- 21938931
TI  - [Phosphorylation of histone H2AX in human lymphocytes as a possible marker of
      effective cellular response to ionizing radiation].
AB  - DNA double-strand breaks (DSBs) which occurs in cells after ionizing radiation
      (IR) or chemical agents are the most dangerous lesions in eukariotic cells, which
      leads to cell death or chromosome abberations and cancer. One of the earliest
      response of cells to DSBs formation is phosphorylation by 139 serine of core
      variant histone H2AX in megabase chromatin domains around DSB (gamma-H2AX), which
      amplify signal and makes it possible to identify even one DSB in genome.
      Effective formation of gamma-H2AX is very important for maintenance of genome
      stability. Here, using immunofluorescent and Western blotting techniques, we
      studied dynamics of gamma-H2AX formation in human lymphocytes of various
      individuals irradiated ex vivo. We have found that dynamics of gamma-H2AX
      formation in lymphocytes differ between individuals but have similar kinetics and
      statistically is independent on people age.

PMID- 21938932
TI  - [The activity of receptor guanylyl cyclases in tissues of rats with neonatal
      streptozotocin diabetus mellitus and the influence of intranasal administration
      of insulin and serotonin].
AB  - Functional activity of hormanal signaling systems and their sensitivity to
      regulatory actions of hormones in diabetes mellitus (DM) and its complications
      are altered. The activity of receptor forms of guanylyl cyclases (rGC) sensitive
      to natriuretic peptides, ANP and CNP, in tissues of female rats with 240-days
      neonatal streptozotocin DM and the influence of intranasal administration of
      insulin and serotonin (6 weeks, daily dose is 0.48 IU of insulin or 20 microg of
      serotonin to rat) on this activity were studied. In diabetic animals, the
      increase of the basal activity of rGC in the myocardium and its decrease in the
      uterus and ovaries were found, whereas the brain showed no differences from
      control animals. The treatment of diabetic rats with insulin led to a decrease in
      the basal activity of rGC in the myocardium and to its restoration to normal
      level in the ovaries. Serotonin treatment induced a less pronounced compared with
      insulin decrease in the basal activity of the enzyme in the myocardium and also a
      slight increase the activity in the brain. In the myocardium of diabetic rats,
      the weakening of GC stimulating effect of ANP and, on the contrary, the
      strengthening of CNP effect were observed. In the ovaries, GC stimulating effect
      of CNP and, to a lesser degree, the corresponding effect of ANP were decreased.
      In the uterus and the brain, the sensitivity of rGC to hormones was practically
      not changed. The administration of insulin to diabetic rats induced an increase
      in GC effect of ANP in the myocardium to its values in control animals and a
      decrease in CNP effect as well as in partially restored GC effect of CNP in the
      ovaries. Serotonin treatment led to some increase in the effects of natriuretic
      peptides in the brain of both control and diabetic animals. Summing up, in
      neonatal model of type 2 DM in the myocardium and the tissues of reproductive
      system of rats the functioning of natriuretic peptide-sensitive rGC is altered in
      the myocardium and the tissues of reproductive system of model rats with neonatal
      type 2 DM. Treatment of animals with insulin substantially restores rGC activity
      while intranasal administration of serotonin has little effect.

PMID- 21938933
TI  - [Signal function of calcium-binding proteins in lower eukaryotes].
AB  - This review summarizes data on the signaling role of calcium-binding proteins
      (CaBP) in lower eukaryotes cells. The contributions of calmodulin (CaM)-like
      proteins, calcium-dependent protein kinases (CDPK), as well as calcineurin B-like
      phosphatase (CaNB) and some other proteins to Ca(2+)-dependent regulation of
      cellular functions is considered.

PMID- 21938934
TI  - [Simulation of parameters of alcohol-oxidizing enzyme systems and
      pathomorphological characteristics in situations of acute ethanol poisoning and
      ischemic heart disease].
AB  - Morphometric characteristics and forensic chemical information used in
      diagnostics of acute ethanol intoxication and coronary heart disease in
      conjunction with macro- and microscopic pathomorphological signs of the changes
      in the heart, liver, and kidneys provide data that may suggest the presence of
      pathology but do not permit to reliably identify it. In this context, evaluation
      of activities of alcohol-oxidizing enzyme systems acquires clinical significance.
      The analysis of correlations between quantitative parameters supplemented by the
      construction of binary models allows to objectively interpret the conclusions
      about the cause of death in each concrete case of acute ethanol poisoning and
      coronary heart disease.

PMID- 21938935
TI  - [Forensic medical diagnostics of the extent of the thigh skin injury inflicted by
      motor vehicles of different weight].
AB  - The authors report the results of an experimental study designed to characterize
      microstructural changes in the thigh skin caused by the impacts simulating the
      car wheel loads of different intensity. It was shown that histological methods
      can be used to discriminate between the intensities of traumatic loading on
      biological tissues.

PMID- 21938936
TI  - [About classification of injuries inflicted on humans by carnivorous animals].
AB  - The biological classification of living species is shown to be inapplicable for
      the purposes of forensic medical examination. A list of the families of
      carnivorous animals that may be of forensic medical significance is presented.
      Their working classification is proposed taking into account the size and
      behaviour of the animals as well as their body parts and organs with which they
      may inflict injuries to man in various situations. The main types of wounds
      caused by carnivores are considered.

PMID- 21938937
TI  - [The detection of RhD antigen of the rhesus system by the real time polymerase
      chain reaction].
AB  - A method for the detection of RhD using a DNA preparation and the newly-developed
      test-system based on the real time polymerase chain reaction is described. The
      study including a large variety of specimens has demonstrated the applicability
      of the novel system to forensic medical examination.

PMID- 21938938
TI  - [Determination of the body length of adult humans from the measurable wrist
      parameters on X-ray image].
AB  - The authors propose methods for the determination of the body length of adult
      persons based on the planimetric analysis of X-ray images of the wrist bones. The
      body length was calculated with the help of regression equations derived with
      reference to the age-specific changes of the wrist bones visible on X-ray images.
      The results of the calculation were compared with the known body length of
      selected subjects.

PMID- 21938939
TI  - [Drug intoxications as an indicator of social tensions and social ill-being].
AB  - Taken together statistical data illustrating the frequency of acute iatrogenic
      intoxication and parameters of economic development of the country testify to the
      importance of the problem of drug abuse confirmed by calculation of Piearson's
      correlation coefficients. The analysis of the rating list of pharmaceutical
      products known to most frequently cause intoxication indicates that a group of
      potentially dangerous' preparations include not only prescription drugs, such as
      neuroleptics, antidepressants, and soporifics, but also over-the-counter
      medicines. The results of the present study give evidence of the appearance of a
      separate nosological form in this country referred to as iatrogenic diseases.
      Moreover, they give reason to regard iatrogenic intoxication as a risk factor of
      social tensions and ill-being.

PMID- 21938940
TI  - [The detection of isoniazide in the cadaveric blood and plasma by high
      performance liquid chromatography with a diode matrix detector].
AB  - The authors describe the analytical procedure for the rapid detection of
      isoniazide in the cadaveric blood and plasma using high performance liquid
      chromatography with a diode matrix detector (HPLC-DAD). The method is designed
      for toxicological and forensic medical analyses. The preliminary preparation of
      the samples includes protein precipitation with trichloroacetic acid, formation
      of isoniazide derivatives with cinnamic aldehyde, and chromatographic analysis on
      an Eclipse XDB-C18 column with registration of absorption at a wavelength of 340
      nm. The mobile phase is a mixture of methanol and 0.05 M ammonium acetate buffer
      (50:50 v/v), pH 3.8. The detection limit is 0.5 mcg/ml in plasma and 1 mcg/ml in
      blood hemolizate. The qualitative determination is possible in a concentration
      range from 2 to 200 mcg/ml. Mean square deviation does not exceed 12% in a
      concentration interval from 2 to 50 mcg/ml.

PMID- 21938941
TI  - [The detection of nifedipine in biological materials].
AB  - The objective of the present study was to find optimal conditions for the
      isolation of nifedipine from biological materials by ethylacetate. It was shown
      that nifedipine can be purified from co-extracted substances of the biological
      material on a Silasorb C-18 column with the size of the particles 30 microns. The
      authors propose to use thin-layer chromatography, IR spectrophotometry, and
      reverse-phase high performance liquid chromatography for the identification and
      quantitative determination of nifedipine extracted from cadaveric liver samples.

PMID- 21938942
TI  - [The application of the videographic images as samples for the comparative
      craniofacial study].
AB  - The results of analysis of 181 forensic medical examinations for craniofacial
      personality identification are presented. Video snapshots of materials used in
      the practical forensic medical work and specimens prepared for experimental
      stdies are shown to be of a higher informative value than conventional
      photographs. The use of life-time video snapshots for the purpose of comparison
      significantly improves the efficacy of craniofacial identification by providing
      much wider opportunities for studying the signs of descriptive portraits,
      comparing skull measurements and life-time video snapshots obtained at different
      head rotations and camera angles, and making use of specific characteristics of
      the stomatological status.

PMID- 21938943
TI  - [On the interaction between State Forensic Medical Centers of the Russian
      Ministry of Defense and territorial organs of the Russian Federal Service on
      Surveillance for Consumer Rights (Roszdravnadzor): topical problems and
      possibilities for their solution].
AB  - The present paper is focused on the consideration of topical problems pertaining
      to the interaction between state forensic medical centers of the Russian Ministry
      of Defense (SFMF MD RF) and territorial organs of the Russian Federal Service on
      Surveillance for Consumer Rights (Roszdravnadzor) in the framework of unscheduled
      inspections of the organization and conduction of forensic medical expertise.
      Such inspections not infrequently give rise to conflicts between the
      administration of SFMF ND RF and commissions of territorial organs of
      Roszdravnadzor. The principal source of such conflicts is the representatives of
      Roszdavnadzor frequently fail to observe the requirements envisaged by the
      normative legal acts of the Russian Federation regulating activities of this
      state agency and the laws of the Russian Federation governing action management
      in the field of forensic medical expertise. The main causes behind the conflicts
      and their consequences are discussed, recommendations are proposed to resolve
      them.

PMID- 21938944
TI  - [Unusual tanatogenesis in a case of combined mechanical asphyxia].

PMID- 21938945
TI  - [Two cases of stab and slash wounds in the vitally important body regions].
AB  - Two cases of severe injuries to the head and the neck are reported. Both patients
      recovered after the traumas.

PMID- 21938946
TI  - [The use of the andragogic model of education at different stages of studying the
      "forensic medicine" discipline].
AB  - The technology of education for adult subjects, i.e. the scientifically-sound
      system of andragogic principles for the education of adults (both teachers and
      learners), is considered. Putting these principles into practice leads with a
      high degree of probability to the achievement of the sought goals of education.
      These principles as well as the andragogic educational model itself are
      recommended for a wider application to the system of education for senior
      students, junior physicians, and resident medical practitioners with a view to
      improving the efficacy of the educational process.

PMID- 21938947
TI  - [Parallels between clinical and morphological characteristics in fetal and
      newborn asphyxia from the standpoint of forensic medicine].
AB  - This paper deals with morphological methods for diagnostics of pre-, intra-, and
      postnatal asphyxia in newborn infants. Parallels between clinical and
      morphological characteristics in fatal cases resulting from this condition are
      described. The analysis of the voluminous literature has demonstrated the
      imperative necessity to broaden the scope of diagnostic morphological and
      pathomorphological methods for the study of newborn baby corpses in order to
      elucidate the causes of death or clarify whether a baby was born alive or
      stillborn.

PMID- 21938948
TI  - [Peculiarities of the research development on toxicological (forensic) chemistry
      based on the analysis of materials published in the volumes of collected reports
      delivered to the All-Russian congresses/plenary meetings of the Society of
      forensic medical experts and scientific/practical conferences during the period
      from 1990 to 2010].

PMID- 21938949
TI  - [Drosophila melanogaster as a model for studying the function of animal viral
      proteins].
AB  - Studies in which Drosophila melanogaster individuals carrying transgenes of
      animal viruses were used to analyze the action of animal viral proteins on the
      cell are reviewed. The data presented suggest that host specificity of viruses is
      determined by their proteins responsible for the penetration of the virus into
      the cell, while viral proteins responsible for interactions with the host cell
      are much less host-specific. Due to this, the model of Drosophila with its
      developed system of searching for genetic interactions can be used to find
      intracellular targets for the action of viral proteins of the second group.

PMID- 21938950
TI  - Study of genotoxicity and antigenotoxicity of the Cotinus coggygria Scop.
      methanol extract by Drosophila melanogaster sex-linked recessive lethal test.
AB  - The genotoxic and antigenotoxic effects of Cotinus coggygria Scop. methanol
      extract was investigated using the Drosophila sex-linked recessive lethal (or
      SLRL) test. The results presented here show that the methanol extract of Cotinus
      coggygria in a concentration of 5% and artificial chemical agent ethyl
      methanesulfonate EMS (0.75 ppm) induce recessive lethal mutations on X-chromosome
      on Drosophila melanogaster in all broods (I, II and III). Post-treatment with
      lower concentration of the methanol extract of Cotinus coggygria (2%) was
      effective in reducing genotoxicity ofmutagen.

PMID- 21938951
TI  - [Role of constitutive and inducible repair in radiation resistance of Escherichia
      coli].
AB  - Radiation resistance of Escherichia coil cells depends on how efficiently DNA is
      recovered after damage, which is determined by the function of constitutive and
      inducible repair branches. The effects of additional mutations of the key genes
      of constitutive and inducible repair (recA, lexA, recB, polA, lig, gyr, recE,
      recO, recR, recJ, recQ, uvrD, helD, recN, and ruv) on radiation resistance were
      studied in E. coli K-12 strain AB 1157 and highly radiation-resistant isogenic
      strain Gam(r)444. An optimal balance ensuring a high gamma resistance of the
      Gam(r)444 radiation-resistant E. coli mutant was due to expression of the key SOS
      repair genes (recA, lexA, recN, and ruv) and activation of the presynaptic
      functions of the RecF homologous recombination pathway as a result of a possible
      mutation of the uvrD gene, which codes for repair helicase II.

PMID- 21938952
TI  - [Mutation analysis of the purine operon leader region in Bacillus subtilis].
AB  - Expression of Bacillus subtilis purine (purE) operon is a subject of double
      negative control involving repressor protein PurR and a transcription terminator
      located in the operon leader region. We have performed site-directed mutagenesis
      of the specific motives, which are involved in formation of alternative hairpin
      structures, one of which produces transcription termination at the leader region
      ofpurEoperon. In vivo and in vitro analyses of the generated mutants have shown
      that purine bases, guanine and hypoxantine, serve as effector metabolites capable
      of increasing stability of terminating hairpin within the leader mRNA. Therefore,
      the leader RNA of purE operon serves as a sensor towards these metabolites and a
      riboswitch that provides premature termination of the operon transcription. The
      synergistic effect of the PurR repressor protein and a transcription terminator
      located at the leader region on the expression of purE operon was also revealed.

PMID- 21938953
TI  - [Bacteriophage phi297--the new species of temperate phages Pseudomonas aeruginosa
      with a mosaic genome: potential use in phagotherapy].
AB  - The genome of halo-forming temperate Pseudomonas aeruginosa phage phi297 and
      lytic activity of its virulent mutant were studied. A mosaic structure was
      revealed for phi297 genome by its complete sequencing. The phi97 genome was
      partly homologous to the genomes of phages D3 and F116. High lytic activity was
      assumed for temperate P. aeruginosa bacteriophage phi297 on the basis of
      morphological features of negative colonies. Virulent mutant phi297vir, which was
      capable oflysing bacteria, while the wild-type phage induced lysogeny, was
      isolated. Lytic activity was compared for phi297 and the phages from commercial
      mixtures of two manufacturers (facilities of Nizhnii Novgorod and Perm'). Phage
      phi297 caused lysis of the mutant PAO1 bacteria that were resistant to the phages
      from commercial preparations, but the lystic activity spectrum of phi297 was
      narrower that the spectra of the commercial phages. The use of nonreverting
      virulent mutants of certain temperate bacteriophages was proposed for the
      treatment of P. aeruginosa infections.

PMID- 21938954
TI  - [Analysis of diversity of Russian and Ukrainian bread wheat (Triticum aestivum
      L.) cultivars for high-molecular-weight glutenin subunits].
AB  - The allelic diversity of high-moleculat-weght glutenin subunits (H WIGS) in
      Russian and Ukrainian bread wheat cultivars was analyzed. The diversity of spring
      wheat cultivars for alleles of the Glu-1 loci is characterized by medium values
      of the polymorphism index (polymorphism information content, PlC), and in winter
      wheats it varies from high at the Glu-A1 locus to low at the Glu-D1 locus. The
      spring and winter cultivars differ significantly in the frequencies of alleles of
      the glutenin loci. The combination of the Glu-A1b, Glu-B1c, and Glu-D1a alleles
      prevails among the spring cultivars, and the combination of the Glu-A1a, Glu-B1c,
      and Glu-D1d alleles prevails among the winter cultivars. The distribution of the
      Glu-1 alleles significantly depends on the moisture and heat supply in the region
      of origin of the cultivars. Drought resistance is associated with the Glu-D1a
      allele in the spring wheat and with the Glu-B1b allele in the winter wheat. The
      sources of the Glu-1 alleles were identified in the spring and wheat cultivars.
      The analysis of independence of the distribution of the spring and winter
      cultivars by the market classes and by the alleles of the HMWGS loci showed a
      highly significant association of the alleles of three Glu-1 loci with the market
      classes in foreign cultivars and independence or a weak association in the
      Russian and Ukrainian cultivars. This seems to be due to the absence of a
      statistically substantiated system of classification of the domestic cultivars on
      the basis of their quality.

PMID- 21938955
TI  - [Polymorphism of lectin genes in Lathyrus plants].
AB  - The carbohydrate-binding sequences of the lectin genes from spring vetchling
      Lathyrus vernus (L.) Bernh., marsh vetchling L. palustris (L.), and Gmelin's
      vetchling L. gmelinii (Fitsch) (Fabaceae) were determined. Computer-aided
      analysis revealed substantial differences between nucleotide and predicted amino
      acid sequences of the lectin gene regions examined in each of the three vetchling
      species tested. In the phylogenetic trees based on sequence similarity of
      carbohydrate-biding regions of legume lectins, the sequences examined formed a
      compact cluster with the lectin genes of the plants belonging to the tribe
      Fabeae. In each plant, L. vernus, L. palustris, and L. gmelinii, three different
      lectin-encoding genes were detected. Most of the substitutions were identified
      within the gene sequence responsible for coding the carbohydrate-binding protein
      regions. This finding may explain different affinity of these lectins to
      different carbohydrates, and as a consequence, can affect the plant host
      specificity upon development of symbiosis with rhizobium bacteria.

PMID- 21938956
TI  - White Kwao Krua variety classification by botanical characteristics and ISSR
      Touchdown PCR technique.
AB  - White Kwao Krua [Pueraria candollei Grah. var. mirifica (Airy Shaw et
      Suvatabandhu) Niyomdham] is a herb used as an ingredient in supplementary and
      cosmetic. The tuberous roots of White Kwao Krua (WKK) contain estrogen-like
      substances. Seeds of WKK, collected from Prachuab Khiri Khan, were planted and
      propagated in the farm of Suranaree University of Technology, and their genetic
      backgrounds were ambiguous. Thirty six plants of WKK in the same age were sampled
      for classification using 7 botanical characteristics and DNA fingerprint by ISSR
      Touchdown PCR technique. The relationship of the 7 botanical characteristics,
      using principle component analysis (PCA), showed the WKK plants fell into 3
      groups. In the first group was plant number 34, which was distinguished from the
      other plants by its small leaf size. The second group consisted of 23 plants with
      elliptic leaf shape, acute leaf base, and acuminate leaf apex. The third group
      consisted of 12 plants with ovate leaf shape, obtuse leaf base, and cuspidate
      leaf apex. The ISSR-Touchdown PCR technique with 41 primers detected 355 loci of
      DNA with an average of 8.6 loci per primer. The sizes of DNA ranged between 280
      bp to 1550 bp. Two hundred ninety three loci exhibited polymorphisms (82.54%) and
      the rest 62 loci were monomorphic (17.46%). The polymorphism information content
      (PIC) was between 0.0315-0.9779 (average 0.4779) and number of effective alleles
      per locus (Ne) ranged between 1.1250-1.8541 (average 1.5544). Unweighted pair
      group method with arithmetic mean (UPGMA), Jaccard similarity coefficient and PCA
      were used to find the construction of genetic relationship of WKK. The genetic
      similarity (GS) of WKK ranged between 0.50-0.86 (average 0.77). At the GS of 0.56
      from cluster analysis, the WKK varieties could be divided into 2 major groups.
      The first group comprised of plant number 34 and 7, and the second group could be
      further divided in 2 subgroups at GS of 0.69. None of the WKK plants was
      identical in genetic, and they were expected to be derived from 5 genetic
      sources. These results showed that applying of the ISSR-Touchdown PCR technique
      could be used to classify WKK efficiently.

PMID- 21938957
TI  - [Allozyme variation of seed embryos and mating system in relict populations of
      Scots pine (Pinus sylvestris L.) from the Kremenets Hill Ridge and Maloe
      Poles'e].
AB  - Allozyme variation at ten polymorphic loci and mating system was studied in three
      small isolated relict populations (4.4 to 22 ha) and in three artificial stands
      of Pinus sylvestris from the Kremenets Hill Ridge and Maloe Poles'e. It was
      established that the mean heterozygosity of 130 to 140 year-old trees from
      natural populations (H(O) = 0.288; H(E) = 0.277) was substantially lower,
      compared to 30 to 40 year-old trees from artificial stands (H(O) = 0.358; H(E) =
      0.330). The observed heterozygosity of seed embryos (H(O) = 0.169 and 0.180) was
      substantially lower than of the mature trees from populations and artificial
      stands, respectively. In the embryo samples, irrespectively of the forest stand
      origin, substantial hetedrozygote deficiency was observed (at six to eight loci),
      compared to the Hardy-Weinberg expectations. The proportion of cross pollination
      in the populations and artificial stands was low, t(m) = 0.588 to 0.721; and t(m)
      = 0.455 to 0.837, respectively.

PMID- 21938958
TI  - [Autosegregation of enzyme loci in agamospermous progenies of triploid plants of
      sugar beet (Beta vulgaris L.)].
AB  - The ratios of the phenotypic classes of glucosephosphate isomerase (GP12) and
      malate dehydrogenase (MDH1 and MDH2) were studied in agamospermous progenies of
      triploid sugar beet plants. The ratio of the phenotypic classes of these enzymes
      corresponds to the calculations based on the assumption of polyteny of
      chromosomes carrying alleles of the enzyme loci accompanied by the loss of extra
      copies of the alleles in the first division of a cell entering embryogenesis. An
      increase in the gene dosage due to polyteny leads to the appearance in the
      progeny with a definite frequency of alleles that were absent in the original
      parental plant. The notions of meiotic autosegregation and mitotic
      autosegregation characteristic of meiotic and mitotic agamospermy are introduced,
      as well as the term locus polygenotype characterizing not only the allelic
      composition and the number of chromosomes, but also the number of chromatids
      carrying alleles of the marker locus in the cell before its entry into
      embryogenesis.

PMID- 21938959
TI  - [Molecular differentiation and taxonomy of the sunwatcher toadheaded agama
      species complex Phrynocephalus superspecies helioscopus (Pallas, 1771) (reptilia:
      agamidae)].
AB  - Lizards of the sunwatcher toad-headed agama species complex Phrynocephalus
      superspecies helioscopus, mostly distributed in Middle Asia and Middle East, were
      examined using analysis of variation at the mitochondrial cytochrome oxidase c
      subunit I gene fragment and fingerprint analysis of nuclear DNA (inter-SINE PCR
      technique). A total of 86 individual tissue samples from 53 populations, to the
      full extent representing different parts of the species complex range, were
      subjected to molecular genetic examination, and surprisingly deep differentiation
      was revealed. The populations analyzed split into 12 isolated phylogroups, many
      of which were characterized by a narrow range and genetic isolation. Monophyly of
      sunwatcher (Ph. helioscopus) and Persian (Ph. persicus) toad-headed agamas was
      confirmed. However, both of these species probably represent the species
      complexes. Zoogeography of Middle Asiais discussed.

PMID- 21938960
TI  - [Meiosis in gray voles of the subgenus microtus (rodentia, arvicolinae) and in
      their hybrids].
AB  - The results of light and electron microscopic (EM) studies of meiosis in Microtus
      arvalis males of the karyoform "arvalis" (2n = 46, NFa = 80), in hybrids between
      the chromosomal forms arvalis and obscurus (2n = 46, NFa = 68), in M.
      rossiaemeridionalis voles (2n = 54, NFa = 54), and in a hybrid between the
      species M. rossiaemeridionalis and M. kermanensis (2n = 54, NFa = 54) are
      presented. SC (synaptonemal complex) karyotypes of the parental forms and the
      hybrids were constructed on the basis of measurements of the length ofautosomal
      SCs revealed by the EM analysis in spermatocytes at the stage of middle
      pachytene. The SC karyotypes of M. arvalis and the hybrids female obscurus x male
      arvalis consist of 22 synaptonemal complexes of autosomal bivalents and the axial
      elements of the synaptonemal complexes of the sex chromosomes X and Y. The SC
      karyotypes of M. rossiaemeridionalis and the hybrid M. rossiaemeridionalis x M.
      kermanensis consist of 26 synaptonemal complexes of autosomal bivalents and a sex
      bivalent; they differ only in the length of the Y chromosome axis (Y chromosome
      in the hybrid was inherited from M. kermanensis). Asynaptic configurations of the
      autosomal SCs were not observed in the hybrids. The SC axial elements of the X
      and Y chromosomes in the parental forms and in the hybrids were located close to
      each other throughout pachytene, but they did not form a synaptic region. The
      normal synapsis in sterile hybrids (M. rossiaemeridionalis x M. kermanensis) and
      the behavior of the sex chromosomes in meiosis in fertile and sterile hybrids are
      discussed in the context of specific features of meiosis and reproductive
      isolation.

PMID- 21938961
TI  - [Evolutionary relationships between reptiles inferred from the comparison of
      their ITS2 sequences].
AB  - The reptile phylogeny is poorly studied, and many existing hypotheses are
      controversial. In this study, the ITS2 regions of 43 species of lizards, snakes,
      turtles, and crocodiles were cloned and sequenced in addition to eight ITS2
      sequences of amphibians, reptiles, and birds already present in the database. The
      ITS2 of reptiles, similarly to other vertebrates, contain short conserved
      (consensus) regions, alternating with variable regions (DI, DII, and DIII), which
      are potentially capable of forming stable secondary structures. These
      functionally neutral rDNA regions, separating the consensus regions, are
      substantially different in size, as well as in the primary and secondary
      structure. Sequences of the ITS2 variable regions were aligned using the GeneBee
      Molecular Biology Server software program with subsequent automated construction
      of prescribed trees. The trees for all three variable regions were highly
      similar, enabling certain conclusions on the evolutionary history of reptiles.

PMID- 21938962
TI  - [Calculation of interpopulation genetic distances at different sample sizes].
AB  - A new method for comparison of interpopulation genetic distances is proposed. The
      method allows a more precise location of populations in the space of genetic
      characters relative to one another at considerably different sample sizes. The
      method consists in multiple reduction of the sample sizes to the size of the
      smallest sample followed by averaging the calculated genetic distances between
      the reduced samples. Software for calculation of genetic distances by this method
      is presented.

PMID- 21938963
TI  - Transcriptional interactions during barley susceptible genotype infection with
      Cochliobolus sativus.
AB  - A systematic sequencing of expressed sequence tags (ESTs) was used to obtain a
      global picture of the assembly of barley genes differentially expressed during
      the hypersensitive reaction of a susceptible genotype in response to an
      incompatible Cochliobolus sativus pathovar. To identify a large number of plant
      ESTs, which are induced at different time points, an amplified fragment length
      polymorphism (AFLP) display of complementary DNA (cDNA) was ulilized. Significant
      transcriptional changes in the host plant occurred already 4 h post inoculation.
      Four hundred and fifty six ESTs have been generated, of which 17 (c. 53% up
      regulated, 47% down-regulated) have no previously described function. On one
      hand, the majority of EST-annotations showed protein synthesis, but genes related
      to signal transduction pathway were also identified. This study provides novel
      global catalogue ofgene regulations involved in C. sativus-barley interaction not
      currently represented in EST databases.

PMID- 21938964
TI  - [Isolation and characterization of twenty-one polymorphic microsatellite loci in
      the Tibetan macaque (Macaca thibetana)].
AB  - Twenty-one microsatellite loci were isolated from AC-enriched library of Tibetan
      macaque (Macaca thibetana). The number of alleles at the 21 microsatellite loci
      ranged from 8 to 15, with an average of 12.2 per locus. Polymorphism information
      content (PIC) ranged from 0.805 to 0.910 with an average of 0.873. The observed
      and expected heterozygosities ranged from 0.208 to 0.792 and from 0.843 to 0.938,
      respectively. These microsatellite loci will be useful for future studies that
      relate to the genetic diversity and population structure of Tibetan macaque.

PMID- 21938965
TI  - Patient satisfaction.

PMID- 21938966
TI  - Data quality assurance: an analysis of patient non-response.
AB  - PURPOSE: Patient satisfaction is paramount to maintaining high clinical quality
      assurance. This study seeks to compare response rates, response bias, and the
      completeness of data between paper and electronic collection modes of a
      chiropractic patient satisfaction survey. DESIGN/METHODOLOGY/APPROACH: A
      convenience sample of 206 patients presenting to a chiropractic college clinic
      were surveyed concerning satisfaction with their chiropractic care. Paper (in
      clinic and postal) and electronic modes of survey administration were compared
      for response rates and non-response bias. FINDINGS: The online data collection
      mode resulted in fewer non-responses and a higher response rate, and did not
      evince response bias when compared to paper modes. The postal paper mode
      predicted non-response rates over the in-clinic paper and online modalities and
      exhibited a gender bias. RESEARCH LIMITATIONS/IMPLICATIONS: This current study
      was a single clinic study; future studies should consider multi-clinic data
      collections. Busy clinic operations and available staff resources restricted the
      ability to conduct a random sampling of patients or to invite all eligible
      patients, therefore limiting the generalizability of collected survey data.
      PRACTICAL IMPLICATIONS: Results of this study will provide data to aid
      development of survey protocols that efficiently, account for available human
      resources, and are convenient for patients while allowing for the most complete
      and accurate data collection possible in an educational clinic setting.
      ORIGINALITY/VALUE: Understanding patient responses across survey modes is
      critical for the cultivation of quality business intelligence within college
      teaching clinic settings. This study bridges measurement evidence from three
      popular data collection modalities and offers support for higher levels of
      quality for web-based data collection.

PMID- 21938967
TI  - Developing criteria for elderly nursing homes: the case of Lebanon.
AB  - PURPOSE: The purpose of this study is to establish a set of measurable criteria
      for elderly nursing homes (ENHs) in Lebanon. Donabedian's model known by
      structure/process/outcome was used as the driving conceptual framework for the
      study. DESIGN/METHODOLOGY/APPROACH: The study reports on a panel discussion where
      administrators, caregivers and specialists, separately established and exchanged
      key information on best practice approach. The work was carried out in the summer
      of 2008, using the consensus panel method. A group of expert opinions (Dalkey)
      made up of elderly home administrators and caregivers, policy makers, and
      academics discussed specific key issues related to elderly health and quality of
      life. FINDINGS: A total of 40 criteria were retained along seven main dimensions:
      types of elderly homes; funding; health services; boarding services; activities;
      structures; and elderly rights. RESEARCH LIMITATIONS/IMPLICATIONS: A major
      limitation in this study is that elderly were not part of the consensus making
      process. Thus, including elderly in the process would have substantiated and
      added validity to the established criteria. PRACTICAL IMPLICATIONS: The criteria
      developed in this study can be turned into key performance standards for elderly
      homes in Lebanon, other Mediterranean and Arab countries. These criteria would
      greatly benefit elderly homes if validated and used as guidelines for quality
      care. ORIGINALITY/VALUE: The study is original in the sense that it seeks to
      establish measures for criteria, a blueprint, and benchmarks for ENH standards.

PMID- 21938968
TI  - Predictors of satisfaction with child birth services in public hospitals in
      Ghana.
AB  - PURPOSE: The purpose of this paper is to examine the association between
      experiences during childbirth and satisfaction with childbirth services.
      DESIGN/METHODOLOGY/APPROACH: A cross-sectional analytical approach using a
      structured questionnaire and exit interviews was employed to gather data from 885
      women who delivered vaginally in two public hospitals. Data were analysed by
      generating frequencies and chi-square which was used in running a binary logistic
      regression using a stepwise backward elimination approach. FINDINGS: With a
      response rate of 78.75 percent the key predictor variables of satisfaction with
      care were: friendliness of staff (OR = 15.12, p = 0.00); the amount of
      information provided on the condition and treatment of women (OR = 9.3857, p =
      0.007); the feeling of being treated with respect (OR = 3.5581, p = 0.023); and
      the provision of information about channels of complaint about care (OR =
      50.0839, p = 0.000). It is therefore recommended that steps be instituted to
      improve client-/health worker interpersonal relationships, to improve the amount
      and quality of information provided to clients, and also to establish formal
      structures for complaint management in hospitals. RESEARCH
      LIMITATIONS/IMPLICATIONS: The study sampled only women with vaginal deliveries,
      considering the fact that women with caesarean deliveries have different
      experiences. Thus views of those with caesarean deliveries are excluded.
      ORIGINALITY/VALUE: Several studies have been conducted in Ghana on issues of
      health service satisfaction and quality, but this is about the first, critically
      looking at satisfaction with child birth services in Ghana.

PMID- 21938969
TI  - Comparison of medication error rates and clinical effects in three medication
      prescription-dispensation systems.
AB  - PURPOSE: Medication errors (MEs) are important in terms of their magnitude and
      severity, and there are numerous systems in place to reduce their occurrence.
      However, the ideal system has not yet been identified. The authors' institution
      uses three different medication prescription-dispensation systems which operate
      simultaneously. ME rates were compared, overall and by phase (prescription,
      transcription and administration) and their overall and specific clinical impact.
      DESIGN/METHODOLOGY/APPROACH: The administration of medicinal products was
      observed directly and compared with medical and nursing prescriptions. Errors and
      adverse events were classified by a consensus of experts. FINDINGS: In the
      traditional system the error prevalence rate was 13.59 per cent, (99 per cent CI,
      12.15-14.61 per cent), in the single dose system it was 6.43 per cent (99 per
      cent CI, 5.53-7.32) and in the electronic prescription system it was 8.86 per
      cent (99 per cent CI, 7.33-10.17). The highest error rates in all phases were
      found in the traditional system. The phase affected by most errors in all three
      models was transcription, and the least affected was administration, except for
      the single dose system, in which prescription was the worst. The effects of
      errors in the administration phase are greater, although less so than with the
      automated system. RESEARCH LIMITATIONS/IMPLICATIONS: The dispensation phase was
      not analyzed. PRACTICAL IMPLICATIONS: A study of errors will enable us to reduce
      their occurrence if we know the most frequent types and in which phase they are
      produced, we will be able to prioritise the areas in which to work and select the
      necessary preventive measures. ORIGINALITY/VALUE: It is possible that automated
      medication dispensation systems reduce error rates and the severity of their
      effects.

PMID- 21938970
TI  - Factors influencing patient satisfaction in primary healthcare clinics in Kuwait.
AB  - PURPOSE: To measure the quality of health care services patient satisfaction is
      used as one of the most important indicators. The study aims to identify factors
      affecting patient's satisfaction at primary health care clinics.
      DESIGN/METHODOLOGY/APPROACH: The data was collected during January 2007 and May
      2007 through a randomly-distributed questionnaire. The questionnaires were
      distributed in primary healthcare clinics that represent all heath care regions
      in Kuwait. A total of 426 completed questionnaires, out of 500, were returned
      resulting in a response rate of 85.2 percent. FINDINGS: The majority (87 percent)
      of the patients responded that the time for communication between physician and
      patient was not enough. Seventy-nine-percent of the surveyed patients said they
      would go to the emergency room of the hospital in future if needed instead of
      going to the primary care clinic. Regarding the quality of the communication
      relationship between physician and patients most of the patients responded
      negatively. Exploratory factor analysis identified six factors and reliability of
      overall scale was found to be 0.61. RESEARCH LIMITATIONS/IMPLICATIONS: One
      limitation to this study was the exclusion of the private sector.
      ORIGINALITY/VALUE: The authors hope that this study identifies areas of
      dissatisfaction that can be quickly remedied and ensures enhancement in the areas
      of satisfaction with ongoing attention and emphasis.

PMID- 21938971
TI  - The market, patient loyalty, patient safety, CABG deaths, patient surveillance,
      cost saving.

PMID- 21938972
TI  - Does patient satisfaction affect patient loyalty?
AB  - PURPOSE: This paper aims to investigate how patient satisfaction affects
      propensity to return, i.e. loyalty. DESIGN/METHODOLOGY/APPROACH: Data from 678
      hospitals were matched using three sources. Patient satisfaction data were
      obtained from Press Ganey Associates, a leading survey firm; process-based
      quality measures and hospital characteristics (such as ownership and teaching
      status) and geographic areas were obtained from the Centers for Medicare and
      Medicaid Services. The frequency with which end-of-life patients return to seek
      treatment at the same hospital was obtained from the Dartmouth Atlas. The study
      uses regression analysis to estimate satisfaction's effects on patient loyalty,
      while holding process-based quality measures and hospital and market
      characteristics constant. FINDINGS: There is a statistically significant link
      between satisfaction and loyalty. Although satisfaction's effect overall is
      relatively small, contentment with certain hospitalization experience may be
      important. The link between satisfaction and loyalty is weaker for high
      satisfaction hospitals, consistent with other studies in the marketing
      literature. RESEARCH LIMITATION/IMPLICATIONS: The US hospitals analyzed are not a
      random sample; the results are most applicable to large, non-profit teaching
      hospitals in competitive markets. PRACTICAL IMPLICATIONS: Satisfaction ratings
      have business implications for healthcare providers and may be useful as a
      management tool for private and public purchasers. ORIGINALITY/VALUE: The paper
      is the first to show that patient satisfaction affects actual hospital choices in
      a large sample. Because patient satisfaction ratings are also correlated with
      other quality measures, the findings suggest a pathway through which individuals
      naturally gravitate toward higher-quality care.

PMID- 21938973
TI  - Factors affecting nurses' perceptions of patient safety.
AB  - PURPOSE: Nurses heavily influence patient care quality and safety. This paper
      aims to examine socioeconomic and organizational/system factors affecting patient
      safety and quality perceptions. DESIGN/METHODOLOGY/APPROACH: A questionnaire was
      constructed to gather demographic, managerial support, information technology
      implementation and integration information. Data were collected from nurses in
      five Riyadh hospitals, Saudi Arabia. Registered nurses working in hospital
      departments participated in the survey. A total of 566 completed questionnaires
      were returned. Subsequent data were analyzed through binary logistic regression.
      FINDINGS: Factors that improve patient safety and the likelihood that nurses use
      their own facility include: fewer visible errors; ability to communicate
      suggestions; information technology support and training; and a confidential
      error reporting system. RESEARCH LIMITATIONS/IMPLICATIONS: The survey was a cross
      sectional study. Consequently, it is difficult to establish causation.
      Furthermore, nursing in these hospitals is dominated by foreign nationals. Also,
      as with all surveys, this research may be subject to response bias. Although the
      questionnaire was randomly distributed, there were no mechanisms to assure
      privacy and minimize peer influence. The high positive patient safety perceptions
      may be influenced by either individual or peer biases. PRACTICAL IMPLICATIONS:
      Nurses are important communicators; especially about hospital safety and quality.
      The research informs leaders about areas that need considering and improving.
      Findings indicate that system factors, including functional feedback,
      suggestions, and error reporting significantly affect patient safety
      improvements. Likewise, nurse education to operate their information systems has
      positive effects. Healthcare leaders need to understand factors that affect
      patient safety perceptions when creating a patient safety culture.
      ORIGINALITY/VALUE: Few international articles examine the factors that influence
      nurses' patient safety perceptions or examine those factors that affect these
      perceptions. This paper adds value by researching what influences patient safety
      perceptions among Riyadh nurses.

PMID- 21938974
TI  - Using dental care resources optimally: quality-efficiency trade-offs in a
      competitive private market.
AB  - PURPOSE: Modern lifestyle changes led to increased dental care needs in India.
      Consequently, there has been a sharp rise in dentist numbers. Karnataka state
      alone produces 2,500 dentists annually, who are engaged in the non-government
      sector owing to inadequate public sector opportunities. This article aims to
      assess Karnataka private dental clinic quality and efficiency.
      DESIGN/METHODOLOGY/APPROACH: Dentists were interviewed using a close-ended,
      structured interview schedule and their clinics were assessed using a checklist
      adopted from guidelines for providing machinery and equipment under the National
      Oral Health Care Programme (NOHCP). Dental "hotel" and clinical quality were
      scored based on this checklist. FINDINGS: Clinical quality was "excellent" in 12
      per cent of clinics and poor in 49 per cent. Clinics with better infrastructure
      charged higher price (p < 0.05). Multi-chair clinics charging fixed rates were
      high (81 per cent). According to 59.5 per cent of dentists, competition did not
      improve quality while 27 per cent felt that competition increased price, not
      quality. About 30.9 per cent of the poor quality clinics, 41 per cent average
      quality clinics and 26 per cent good quality clinics were technically efficient.
      PRACTICAL IMPLICATIONS: The multi chair clinics offered better quality at higher
      prices and single chair clinics provided poorer quality at lower prices. In other
      words, they had a sub-optimal price-quality mix. Therefore, there is a need to
      regulate price and quality in all clinics to arrive at an optimal price-quality
      mix so that clients are not overburdened financially even while receiving good
      quality dental care. ORIGINALITY/VALUE: The article advocates that resources are
      used optimally as a way to achieve value for money and to achieve break-even
      points thereby providing quality care in a competitive market. Factors that
      influence dental practitioner behaviour are evaluated.

PMID- 21938975
TI  - In-hospital mortality rates after CABG by autonomous regions in Spain.
AB  - PURPOSE: The paper's purpose is twofold: to provide a predictive model for
      estimating in-hospital mortality rates after coronary artery bypass grafting
      (CABG) in Spanish autonomous regions (AR) after adjusting relevant factors; and
      to determine whether there is a difference between expected and observed
      mortality rates. DESIGN/METHODOLOGY/APPROACH: All patients registered in a
      minimum basic data set (MSBD) undergoing CABG between 2000 and 2004 were
      selected. After bivariate analysis to explore associations between in-hospital
      death and other variables, a multivariate analysis using logistic regression was
      conducted. The predictive model was evaluated using calibration and
      discrimination techniques. Standardized mortality ratios by AR were calculated.
      FINDINGS: The expected Spanish in-hospital mortality rate after CABG was 7.68 and
      the observed rate was 7.69 deaths per 100 operations. Discrimination obtained
      with the model resulted in an area under the curve of 0.70 (95 per cent CI, 0.69
      0.71). When each AR's mortality rate is calculated and compared with the observed
      rate, some ARs present an observed mortality rate higher or lower than the
      expected rate according to adjusted variables in the model. RESEARCH
      LIMITATIONS/IMPLICATIONS: The MSBD registry does not contain patients' critical
      data, such as arterial damage severity, or in which hospital procedures were
      performed. PRACTICAL IMPLICATIONS: There are factors related to individual
      patient variation, financial resources or healthcare quality in different ARs,
      which should be investigated in follow-up studies. ORIGINALITY/VALUE: The paper
      shows that, although the global expected mortality rate is almost the same as the
      observed Spanish mortality rate, this similarity disappears when AR rates are
      compared.

PMID- 21938976
TI  - A computerized surveillance system for asthma.
AB  - PURPOSE: Asthma is a chronic inflammatory airways disease characterized by acute
      exacerbations interspaced by symptom-free periods. Its management imposes a
      substantial burden on healthcare services, as well as personal suffering and
      significant financial tolls. The aim of this paper is to demonstrate links
      between routinely used computerized databases and to establish an automatic
      mechanism for monitoring asthma patients. DESIGN/METHODOLOGY/APPROACH: The study
      population was all adult subscribers to a major health maintenance organization
      (HMO) in Southern Israel (230,000 adults, age 20-65 years). Relevant data for
      this retrospective analysis (2000 to 2004) were extracted from several
      computerized databases routinely used in the service: pharmacy; administrative;
      and each person's personal computerized medical file in the primary care clinic.
      FINDINGS: Based on data from 72 regional primary care clinics, during the study
      period, 11,054 adults were treated simultaneously by beta2 agonists and steroids-
      assumed to be asthmatics. In contrast, asthma diagnosis was recorded in only
      4,061 personal files. The intersection between two databases yielded 2,569
      persons recorded in both. These findings attest to the feasibility of developing
      computerized automatic surveillance systems for monitoring asthma patients with
      certain algorithms to assure service quality. RESEARCH LIMITATIONS/IMPLICATIONS:
      Data extracted from the various databases were unequal quality, a factor that
      imposed data management difficulties. PRACTICAL IMPLICATIONS: Similar
      surveillance systems can be developed relatively easily by using comparable
      algorithms for monitoring different chronic diseases or introducing management
      indices to secure quality of services. ORIGINALITY/VALUE: The paper focuses on
      developing an automatic asthma monitoring model, using information from routinely
      used computerized HMO DBs.

PMID- 21938977
TI  - Hospital cost structure in the USA: what's behind the costs? A business case.
AB  - PURPOSE: Hospital costs in the USA are a large part of the national GDP. Medical
      billing and supplies processes are significant and growing contributors to
      hospital operations costs in the USA. This article aims to identify cost drivers
      associated with these processes and to suggest improvements to reduce hospital
      costs. DESIGN/METHODOLOGY/APPROACH: A Monte Carlo simulation model that uses
      @Risk software facilitates cost analysis and captures variability associated with
      the medical billing process (administrative) and medical supplies process
      (variable). The model produces estimated savings for implementing new processes.
      FINDINGS: Significant waste exists across the entire medical supply process that
      needs to be eliminated. Annual savings, by implementing the improved process,
      have the potential to save several billion dollars annually in US hospitals. The
      other analysis in this study is related to hospital billing processes. Increased
      spending on hospital billing processes is not entirely due to hospital
      inefficiency. RESEARCH LIMITATIONS/IMPLICATIONS: The study lacks concrete data
      for accurately measuring cost savings, but there is obviously room for
      improvement in the two US healthcare processes. This article only looks at two
      specific costs associated with medical supply and medical billing processes,
      respectively. PRACTICAL IMPLICATIONS: This study facilitates awareness of
      escalating US hospital expenditures. Cost categories, namely, fixed, variable and
      administrative, are presented to identify the greatest areas for improvement.
      ORIGINALITY/VALUE: The study will be valuable to US Congress policy makers and US
      healthcare industry decision makers. Medical billing process, part of a
      hospital's administrative costs, and hospital supplies management processes are
      part of variable costs. These are the two major cost drivers of US hospitals'
      expenditures that were examined and analyzed.

PMID- 21938978
TI  - Sport practice and nutritional habits are linked.

PMID- 21938979
TI  - High dose chemotherapy and stem cell rescue for metastatic germ cell tumours:
      long-term results from a single institution.
AB  - PURPOSE: To evaluate the long term results and the characteristics of patients
      treated with high dose chemotherapy (HDCT) for an advanced germ cell tumour at
      Ghent University Hospital from 1996 to 2010. MATERIALS AND METHODS: A
      retrospective analysis of patients treated with HDCT for germ cell tumours was
      performed. Data about stage at diagnosis, different prognostic scoring systems,
      timing of HDCT, response to HDCT and relapse-free period were collected. The
      following endpoints were evaluated: complete or incomplete response to HDCT,
      relapse free survival and overall survival time. RESULTS: Of the 148 patients
      treated with chemotherapy for an advanced germ cell tumour from 1996 to 2010, 10
      (6.8%) needed salvage treatment by means of HDCT. Six patients achieved a
      complete response to one cycle of HDCT and 2 additional patients achieved a
      complete response to a second cycle of HDCT. A retrospective analysis showed 8
      long-term survivors with a maximum follow-up time of 152 months. Two patients
      were recently transplanted and are not evaluable for survival yet. CONCLUSIONS:
      Our study suggests that long-term survival can be obtained by means of HDCT for
      metastatic germ cell tumours, even in patients with bad prognostic features at
      diagnosis. The question of whether to use 1 or 2 cycles of HDCT still remains
      unanswered.

PMID- 21938980
TI  - Cardiovascular toxicity of cancer treatment.
AB  - Drugs with potential cardiac toxicity are prominent in cancer treatment, not only
      the old chemotherapeutic agents, but also the newer targeted drugs and biologic
      agents. As the long-term survival of patients with malignancies has improved and
      cancer turned into a chronic disease, physicians must take into account the short
      term as well as long-term consequences of cancer treatment, such as chemotherapy
      induced cardiotoxicity. We summarize some general characteristics and
      subsequently review specific antineoplastic agents that are associated with
      cardiac toxicity.

PMID- 21938981
TI  - Matrix-assisted laser desorption ionization-time of flight mass spectrometry for
      the identification of bacteria and yeasts in a clinical microbiological
      laboratory: a review.
AB  - Recently, MALDI-TOF MS devices designed for use in clinical laboratories have
      been commercially introduced in various large centres worldwide. All published
      studies conclude that MALDI-TOF MS can be implemented easily for routine
      identification of bacteria and yeasts in a clinical microbiological laboratory.
      Although all data show that MALDI-TOF MS correctly identifies the great majority
      of isolates processed routinely, it cannot yet identify every such isolate. Until
      today, MALDI-TOF MS is inappropriate for the identification of Shigella species,
      pneumococci and viridans streptococci. Database upgrades and sample enrichment
      are essential elements to refine the MALDI-TOF MS technique, allowing the method
      to increase its power. For the identification of a significant proportion of
      yeasts, an extraction method prior to analysis in the mass spectrometer is
      mandatory to obtain appropriate spectra. Because of the low marginal costs, and
      the extreme speed of MALDI-TOF MS, the technique can improve laboratory
      efficiency when used early in identification protocols. Lengthier, more labour
      intensive, and costlier techniques can be reserved for the minority of isolates
      not identified with high confidence by MALDI-TOF MS. MALDI-TOF MS also has the
      potential to directly identify pathogens in biological fluids, such as urine
      samples and blood cultures. For this application however, further well-designed
      prospective studies are warranted. The potential for identification at the
      serotype or strain level, and antibiotic resistance profiling within minutes make
      MALDI-TOF mass spectrometry an ongoing revolution in the clinical microbiology
      laboratory.

PMID- 21938982
TI  - Lymph node biopsies in a general internal medicine department: algorithm or
      individualized decision-making?
AB  - BACKGROUND: Lymphadenopathy (LA) imposes a diagnostic challenge in internal
      medicine. Exclusion of malignancy is the primary concern. METHODS: A
      retrospective case series, including 40 adult patients from the general internal
      medicine department who underwent lymph node biopsy (LNB) at a single university
      hospital. Demographics, clinical data and histopathological diagnoses were
      registered. By means of the latest medical record, we obtained a final diagnosis
      for each patient and subsequently searched for variables correlated with
      malignancy. Follow-up was at least one year in 95% of cases. RESULTS: The
      prevalence of malignancy was 58%. Older age (p = 0.02) was significantly
      correlated with malignancy. The presence of painful lymphadenopathy at clinical
      examination (p = 0.02) was significantly associated with a benign outcome. No
      single or combination of baseline variables satisfactorily excluded malignancy.
      Histopathological analysis correctly predicted malignancy in 93% of cases. In two
      cases, an initial diagnosis of benign non-specific lymphadenopathy was reversed
      to non-Hodgkin lymphoma. In one case the pathological diagnosis was inconclusive.
      CONCLUSION: Rather than following a universal algorithm to determine the need for
      LNB in patients with LA, we call for individualized decision-making in each case,
      carefully appreciating all available information. Additionally, one should keep
      in mind that false-negative results occur due to sampling errors. Therefore, a
      minimal number of cases should end with a final diagnosis of benign non-specific
      lymphadenopathy. Intensive, multidisciplinary cooperation with surgeon and
      pathologist is needed. Moreover, clinical follow-up should be at least one year.

PMID- 21938983
TI  - Nutritional intake evolution in adolescent sporting boys over the last two
      decades.
AB  - The AIM of the study was to evaluate the nutritional trends in young elite male
      soccer players, attending national soccer league at RFC Bruges over the last two
      decades. At the start of each season, players and parents are instructed about
      normal healthy nutrition and fluid intake by dieticians. METHODS: Since 1983,
      dieticians perform dietary habit surveys in the adolescent player groups. They
      instruct players and parents how to record all food and fluid intake during 3
      days, a training-day, a match-day and an off -day. It is asked to do the
      recordings when players and parents are together and parents are asked to
      supervise the recording. Intakes are calculated using the Becel institute
      nutrition software (BINS), Becel, 2003. RESULTS: A significant decrease of energy
      intake/m2 is observed over the last 20 years. Body composition, measured as age
      matched body mass index remained at median levels for the population during this
      period. An important modification of dietary content towards the recommended
      daily intakes is observed. Fat, saturated fat and cholesterol intake decreased
      dramatically. Carbohydrate intake increased. CONCLUSIONS: A positive evolution
      towards the recommended dietary composition is observed over the years. However,
      the decrease in caloric intake without influence on the body mass index could
      suggest that these elite male footballers have a decreased physical activity as
      compared to 20 years ago.

PMID- 21938984
TI  - Breast cancer prevention: lifestyle changes and chemoprevention.
AB  - Susceptibility to breast cancer is caused by a combination of genetic and
      environmental factors. Research is exploring which factors influence breast
      cancer risk, and by which mechanisms they exert their influence. Women should be
      informed about lifestyle factors influencing their life time breast cancer risk
      and encouraged by their physician to adapt changes in diet, physical activity,
      reproductive issues and use of hormone substitution after menopause, to minimize
      the risk. Patients identified as high risk to develop breast cancer can consider
      prophylactic surgery, chemo-preventive therapies and take part in personalized
      screening programs.

PMID- 21938985
TI  - Excessive eosinophilia as paraneoplastic syndrome in a patient with non-small
      cell lung carcinoma: a case report and review of the literature.
AB  - Hypereosinophilia is a phenomenon which is associated with a broad variety of
      allergic, infectious, paraneoplastic and systemic diseases. Depending on the
      aetiology, these disorders differ in severity from self-limiting to life
      threatening. Although it is well known that hypereosinophilia can occur in
      association with a solid tumour, exact numbers of incidence are lacking. We
      describe a patient with respiratory insufficiency and an elevated level of
      eosinophils in the peripheral blood. A diagnostic work-up revealed the presence
      of a disseminated non-small-cell carcinoma of the lung; an association not
      frequently described.

PMID- 21938986
TI  - Tako-tsubo cardiomyopathy with left ventricular outflow tract (LVOT) obstruction:
      case report and review of the literature.
AB  - In this report, we describe a case of Tako-Tsubo cardiomyopathy (TTC)--also
      called 'apical ballooning' syndrome--in which transient left ventricular outflow
      tract (LVOT) obstruction and mitral regurgitation led to haemodynamic
      instability. Patients with hypotension should undergo urgent echocardiography to
      determine if LVOT obstruction is present. This complication has been described in
      10-25% of all TTC patients. In patients with hypotension and moderate-to-severe
      LVOT obstruction, inotropic agents should not be used because they can worsen the
      degree of obstruction. Instead, it is suggested to use beta-blockers, which can
      improve haemodynamics by causing resolution of the obstruction. The fact that
      some patients do not survive their acute TTC event only underscores the
      importance of prompt recognition and targeted management of dynamic LVOT
      obstruction.

PMID- 21938987
TI  - Collision in the colon: concurrent adenocarcinoma and diffuse large B-cell
      lymphoma in the same tumour.
AB  - Double malignancies in the gastrointestinal tract are unusual. Concurrent
      lymphoma and adenocarcinoma is a rare clinical condition. We herein report a
      collision tumour which first presented with a diffuse large B-cell lymphoma in
      the skull base and ileocecal junction area. After rituximab and chemotherapy the
      skull base tumour disappeared, but the ileocecal lesion remained. A biopsy
      revealed the presence of adenocarcinoma in the same lesion. The tumour was
      surgically removed. Further microscopic examination of the tumour showed it was
      an adenocarcinoma but residual lymphoma cell infiltration could still be
      observed. Serum Epstein-Barr virus (EBV) was detected at diagnosis of lymphoma
      and the concentration further elevated at diagnosis of adenocarcinoma. Therefore,
      both lymphoma and carcinoma may be EBV related. Our experience illustrated that
      such collision tumours are rare and difficult in diagnosis. Clinicians and
      pathologists should be aware of such an association in order to make a correct
      diagnosis and initiate proper treatment.

PMID- 21938988
TI  - Multicentric plasma cell variant Castleman's disease presenting with cutaneous
      vasculitis and pulmonary parenchymal involvement in a patient with ankylosing
      spondylitis: case report and review of the literature.
AB  - We present a case of the multicentric plasma cell variant of Castleman's disease
      (CD) with two rare manifestations. The patient consulted us because of cutaneous
      vasculitis of the lower limbs, while constitutional symptoms were nearly absent.
      Imaging studies also revealed pulmonary parenchymal involvement. Furthermore, our
      patient is the first case in whom association of ankylosing spondylitis with CD
      is reported. In addition, we present a review of the literature with emphasis on
      the clinical presentation of CD and its difficult discrimination from autoimmune
      and infectious disorders. An overview of the therapeutic options is also
      provided.

PMID- 21938989
TI  - Large thymic carcinoma presenting with right ventricular failure: a case report.
AB  - Thymic carcinoma is an overall rare tumour with variable clinical manifestations.
      Right ventricular failure remains an uncommon occurrence and has not been
      reported in literature so far. A 40-year-old lady presented with the complaints
      of progressively worsening retrosternal chest pain, shortness of breath, easy
      fatigability and cough since 1 year. Computed tomography scan of the thorax
      revealed a mass measuring 12 x 10 cm in the anterior mediastinum. This mass
      appeared to be adherent to both lungs and pericardium and was impinging on the
      right atrium and right ventricle. It appeared to be infiltrating the ascending
      aorta, pulmonary arteries and superior vena cava. Ultrasound of the abdomen
      showed hepatomegaly and moderate ascites. Echocardiography showed evidence of
      right ventricular dysfunction as well as elevated right ventricular systolic
      pressures secondary to extrinsic compression. Percutaneous biopsy of the thymus
      was performed showing a malignant thymoma. Radical thymectomy with resection of
      pericardium was planned. Intra-operatively, the tumour was separated from the
      right and left lungs, pulmonary artery and aortic arch. Morphologically,
      immunochemically and clinically, the features were consistent with those seen in
      Masoka stage III thymic carcinoma. She also received six cycles of chemotherapy
      (PAC regimen) including cisplatin (50 mg/m2), doxorubicin (50 mg/m2) and
      cyclophosphamide (500 mg/m2). Radiation therapy in the adjuvant setting was
      planned but the patient was lost to follow-up after 4 months. Although right
      ventricular failure is a very rare presentation of thymic carcinoma, clinicians
      should be aware of this presentation to appreciate the complete clinical spectrum
      of presentation of this neoplasm.

PMID- 21938990
TI  - Mycobacterium marinum infection causing extensive tissue destruction in a hypoxic
      COPD patient.
AB  - We report a skin Mycobacterium marinum infection presenting as wide ulcerative
      lesions of the arm (4 cm for the widest) in a hypoxic COPD patient who takes 4 mg
      methylprednisolone daily and higher doses during exacerbations. Diagnostic delay
      as well as glucocorticoid use could be responsible for the extension of the
      lesions. Clinical resolution occurred after three months of antibiotic therapy.
      Extensive ulcerative lesions are uncommon in Mycobacterium marinum infection in
      an immunocompetent host. This case emphasizes the potential and unusual harmful
      effect of long-term glucocorticoid therapy used in obstructive lung disease on
      the spread of Mycobacterium marinum infection.

PMID- 21938991
TI  - Left atrial myxoma. Evaluation with transoesophageal echocardiographic and real
      time three-dimensional imaging.
AB  - Myxoma is the most common benign cardiac neoplasm. A 66-year-old woman presented
      with a large left atrial myxoma, which was detected by a real-time three
      dimensional echocardiography (RT3DE) and a real-time three-dimensional
      transoesophageal echocardiography (RT3D-TEE) approach. RT3DE and RT3D-TEE proved
      to be techniques that can provide additional contributions to the diagnostic
      investigation of structural heart diseases.

PMID- 21938992
TI  - Diabetic eruptive xanthoma.

PMID- 21938993
TI  - Radiation induced cardiovascular disease.

PMID- 21938994
TI  - What is the presentation of renal angiomyolipomas?

PMID- 21938995
TI  - [Of life responsibility and illusionary self determination].

PMID- 21938996
TI  - [One year minimum nursing pay: labor official states "We must swallow many a
      toad!" (interview by Christian Heinemeyer)].

PMID- 21938997
TI  - [Palliative medicine and palliative nursing: between nursing care and terminal
      care. "Certified dying" is not available].

PMID- 21938998
TI  - [Ethical uncertainty about the end of life. The is no obligation to live].

PMID- 21938999
TI  - [Dementia: reflections on terminal care. "Death does not touch him at the core"].

PMID- 21939000
TI  - [Acupressure for the dying. Alleviating suffering with ancient knowledge].

PMID- 21939001
TI  - [Enhanced awareness near death - an overview for nurses. Take visions
      seriously!].

PMID- 21939002
TI  - [Palliative accompaniment in dying. Not abandoning dying patients].

PMID- 21939003
TI  - [Family health nursing - a profession with much potential. A nurse for all
      cases].

PMID- 21939004
TI  - [Aroma therapy for seriously ill and dying patients. Not a miracle cure but a
      wonderful tool].

PMID- 21939005
TI  - [Clinical pathways in terminal care. Do clinical pathway for terminal care
      improve symptoms and quality of life of patients and family?].

PMID- 21939006
TI  - [Building an intranet portal for Gelderland life support. Knowledge for all!].

PMID- 21939007
TI  - [History of the nursing process. Justice helped boost the classics].

PMID- 21939008
TI  - [The will of the mentally incompetent patient. Patient advance directives in
      general practice].

PMID- 21939009
TI  - [Terminal care for patients with dementia. Being cared for to the end].

PMID- 21939010
TI  - [Recognizing and understanding illnesses. Syncope and fainting].

PMID- 21939011
TI  - [MVVO: interdisciplinary veterinary responsibility].

PMID- 21939012
TI  - [Constipated].

PMID- 21939013
TI  - ["As an expert you have to stick to the facts"].

PMID- 21939014
TI  - [Surveillance].

PMID- 21939015
TI  - [Heart failure due to atrial standstill in a cat].
AB  - A 7.5-year-old male Persian cat with a history of asymptomatic hypertrophic
      cardiomyopathy was examined for severe lethargy and dyspnoea. Physical
      examination revealed bradycardia (60 beats/ minute), and ECG investigation
      revealed persistent atrial standstill that was most likely caused by atrial
      fibrosis. Persistent atrial standstill is a very rare cardiac condition in cats
      and is characterized by a complete lack of mechanical, electrical, and possibly
      endocrine function of the atria. Several pathophysiological mechanisms can cause
      atrial standstill and include hyperkalaemia, intoxication, and atrialfibrosis. On
      the basis of the clinical findings, atrial fibrosis was the most likely cause of
      atrial standstill in this cat. Treatment depends on the underlying cause, but
      pacemaker implantation can be considered if there are structural abnormalities.
      The prognosis is guarded in such cases. In this particular case, the cat was
      euthanized at the owner's request.

PMID- 21939016
TI  - [Stillborn calves with a swollen neck].

PMID- 21939017
TI  - [Antibiotics; from how they work to antibacterial therapy. Part III (of IV)].

PMID- 21939018
TI  - [Three months of prednisolone is enough treatment for IHA].

PMID- 21939019
TI  - [Money does not motivate, but a heart felt "Thank you"].

PMID- 21939020
TI  - [Movir: Prevention program veterinarians terminated on a positive note].

PMID- 21939021
TI  - [A century of veterinary medicine of companion animals].

PMID- 21939022
TI  - [Swine feed].

PMID- 21939023
TI  - [Positive interaction with improved animal welfare].

PMID- 21939024
TI  - [Rien Dobbelaar: from central animal laboratories to animal welfare].

PMID- 21939025
TI  - [Cydectin Triclamox: one product, two problems].

PMID- 21939026
TI  - [Tilburgs initiative helps poor animal owners].

PMID- 21939027
TI  - Life center: filling the needs of geriatric patients in the community, building
      educational experiences.

PMID- 21939028
TI  - Different scientific approaches; one goal.

PMID- 21939029
TI  - Customizing a dental education.

PMID- 21939030
TI  - School develops 10-year master plan: defining facilities needs, setting
      priorities.

PMID- 21939031
TI  - Strong response of an invasive plant species (Centaurea solstitialis L.) to
      global environmental changes.
AB  - Global environmental changes are altering interactions among plant species,
      sometimes favoring invasive species. Here, we examine how a suite of five
      environmental factors, singly and in combination, can affect the success of a
      highly invasive plant. We introduced Centaurea solstitialis L. (yellow
      starthistle), which is considered by many to be California's most troublesome
      wildland weed, to grassland plots in the San Francisco Bay Area. These plots
      experienced ambient or elevated levels of warming, atmospheric CO2,
      precipitation, and nitrate deposition, and an accidental fire in the previous
      year created an additional treatment. Centaurea grew more than six times larger
      in response to elevated CO2, and, outside of the burned area, grew more than
      three times larger in response to nitrate deposition. In contrast, resident
      plants in the community responded less strongly (or did not respond) to these
      treatments. Interactive effects among treatments were rarely significant. Results
      from a parallel mesocosm experiment, while less dramatic, supported the pattern
      of results observed in the field. Taken together, our results suggest that
      ongoing environmental changes may dramatically increase Centaurea's prevalence in
      western North America.

PMID- 21939032
TI  - The efficacy of salvage logging in reducing subsequent fire severity in conifer
      dominated forests of Minnesota, U.S.A.
AB  - Although primarily used to mitigate economic losses following disturbance,
      salvage logging has also been justified on the basis of reducing fire risk and
      fire severity; however, its ability to achieve these secondary objectives remains
      unclear. The patchiness resulting from a sequence of recent disturbances
      blowdown, salvage logging, and wildfire-provided an excellent opportunity to
      assess the impacts of blowdown and salvage logging on wildfire severity. We used
      two fire-severity assessments (tree-crown and forest-floor characteristics) to
      compare post-wildfire conditions among three treatment combinations (Blowdown
      Salvage-Fire, Blowdown-Fire, and Fire only). Our results suggest that salvage
      logging reduced the intensity (heat released) of the subsequent fire. However,
      its effect on severity (impact to the system) differed between the tree crowns
      and forest floor: tree-crown indices suggest that salvage logging decreased fire
      severity (albeit with modest statistical support), while forest-floor indices
      suggest that salvage logging increased fire severity. We attribute the latter
      finding to the greater exposure of mineral soil caused by logging operations;
      once exposed, soils are more likely to register the damaging effects of fire,
      even if fire intensity is not extreme. These results highlight the important
      distinction between fire intensity and severity when formulating post-disturbance
      management prescriptions.

PMID- 21939033
TI  - A synthesis of current knowledge on forests and carbon storage in the United
      States.
AB  - Using forests to mitigate climate change has gained much interest in science and
      policy discussions. We examine the evidence for carbon benefits, environmental
      and monetary costs, risks and trade-offs for a variety of activities in three
      general strategies: (1) land use change to increase forest area (afforestation)
      and avoid deforestation; (2) carbon management in existing forests; and (3) the
      use of wood as biomass energy, in place of other building materials, or in wood
      products for carbon storage. We found that many strategies can increase forest
      sector carbon mitigation above the current 162-256 Tg C/yr, and that many
      strategies have co-benefits such as biodiversity, water, and economic
      opportunities. Each strategy also has trade-offs, risks, and uncertainties
      including possible leakage, permanence, disturbances, and climate change effects.
      Because approximately 60% of the carbon lost through deforestation and harvesting
      from 1700 to 1935 has not yet been recovered and because some strategies store
      carbon in forest products or use biomass energy, the biological potential for
      forest sector carbon mitigation is large. Several studies suggest that using
      these strategies could offset as much as 10-20% of current U.S. fossil fuel
      emissions. To obtain such large offsets in the United States would require a
      combination of afforesting up to one-third of cropland or pastureland, using the
      equivalent of about one-half of the gross annual forest growth for biomass
      energy, or implementing more intensive management to increase forest growth on
      one-third of forestland. Such large offsets would require substantial trade-offs,
      such as lower agricultural production and non-carbon ecosystem services from
      forests. The effectiveness of activities could be diluted by negative leakage
      effects and increasing disturbance regimes. Because forest carbon loss
      contributes to increasing climate risk and because climate change may impede
      regeneration following disturbance, avoiding deforestation and promoting
      regeneration after disturbance should receive high priority as policy
      considerations. Policies to encourage programs or projects that influence forest
      carbon sequestration and offset fossil fuel emissions should also consider major
      items such as leakage, the cyclical nature of forest growth and regrowth, and the
      extensive demand for and movement of forest products globally, and other
      greenhouse gas effects, such as methane and nitrous oxide emissions, and
      recognize other environmental benefits of forests, such as biodiversity, nutrient
      management, and watershed protection. Activities that contribute to helping
      forests adapt to the effects of climate change, and which also complement forest
      carbon storage strategies, would be prudent.

PMID- 21939034
TI  - River restoration: the fuzzy logic of repairing reaches to reverse catchment
      scale degradation.
AB  - River restoration is an increasingly common approach utilized to reverse past
      degradation of freshwater ecosystems and to mitigate the anticipated damage to
      freshwaters from future development and resource-extraction activities. While the
      practice of river restoration has grown exponentially over the last several
      decades, there has been little empirical evaluation of whether restoration
      projects individually or cumulatively achieve the legally mandated goals of
      improving the structure and function of streams and rivers. New efforts to
      evaluate river restoration projects that use channel reconfiguration as a
      methodology for improving stream ecosystem structure and function are finding
      little evidence for measurable ecological improvement. While designed channels
      may have less-incised banks and greater sinuousity than the degraded streams they
      replace, these reach-scale efforts do not appear to be effectively mitigating the
      physical, hydrological, or chemical alterations that are responsible for the loss
      of sensitive taxa and the declines in water quality that typically motivate
      restoration efforts. Here we briefly summarize this new literature, including the
      collection of papers within this Invited Feature, and provide our perspective on
      the limitations of current restoration.

PMID- 21939035
TI  - Effects of urbanization and urban stream restoration on the physical and
      biological structure of stream ecosystems.
AB  - Streams, as low-lying points in the landscape, are strongly influenced by the
      stormwaters, pollutants, and warming that characterize catchment urbanization.
      River restoration projects are an increasingly popular method for mitigating
      urban insults. Despite the growing frequency and high expense of urban stream
      restoration projects, very few projects have been evaluated to determine whether
      they can successfully enhance habitat structure or support the stream biota
      characteristic of reference sites. We compared the physical and biological
      structure of four urban degraded, four urban restored, and four forested streams
      in the Piedmont region of North Carolina to quantify the ability of reach-scale
      stream restoration to restore physical and biological structure to urban streams
      and to examine the assumption that providing habitat is sufficient for biological
      recovery. To be successful at mitigating urban impacts, the habitat structure and
      biological communities found in restored streams should be more similar to
      forested reference sites than to their urban degraded counterparts. For every
      measured reach- and patch-scale attribute, we found that restored streams were
      indistinguishable from their degraded urban stream counterparts. Forested streams
      were shallower, had greater habitat complexity and median sediment size, and
      contained less-tolerant communities with higher sensitive taxa richness than
      streams in either urban category. Because heavy machinery is used to regrade and
      reconfigure restored channels, restored streams had less canopy cover than either
      forested or urban streams. Channel habitat complexity and watershed impervious
      surface cover (ISC) were the best predictors of sensitive taxa richness and
      biotic index at the reach and catchment scale, respectively. Macroinvertebrate
      communities in restored channels were compositionally similar to the communities
      in urban degraded channels, and both were dissimilar to communities in forested
      streams. The macroinvertebrate communities of both restored and urban degraded
      streams were correlated with environmental variables characteristic of degraded
      urban systems. Our study suggests that reach-scale restoration is not
      successfully mitigating for the factors causing physical and biological
      degradation.

PMID- 21939036
TI  - Twenty years of stream restoration in Finland: little response by benthic
      macroinvertebrate communities.
AB  - The primary focus of many in-stream restoration projects is to enhance habitat
      diversity for salmonid fishes, yet the lack of properly designed monitoring
      studies, particularly ones with pre-restoration data, limits any attempts to
      assess whether restoration has succeeded in improving salmonid habitat. Even less
      is known about the impacts of fisheries-related restoration on other, non-target
      biota. We examined how restoration aiming at the enhancement of juvenile brown
      trout (Salmo trutta L.) affects benthic macroinvertebrates, using two separate
      data sets: (1) a before-after-control-impact (BACI) design with three years
      before and three after restoration in differently restored and control reaches of
      six streams; and (2) a space-time substitution design including channelized,
      restored, and near-natural streams with an almost 20-year perspective on the
      recovery of invertebrate communities. In the BACI design, total macroinvertebrate
      density differed significantly from before to after restoration. Following
      restoration, densities decreased in all treatments, but less so in the controls
      than in restored sections. Taxonomic richness also decreased from before to after
      restoration, but this happened similarly in all treatments. In the long-term
      comparative study, macroinvertebrate species richness showed no difference
      between the channel types. Community composition differed significantly between
      the restored and natural streams, but not between restored and channelized
      streams. Overall, the in-stream restoration measures used increased stream
      habitat diversity but did not enhance benthic biodiversity. While many
      macroinvertebrates may be dispersal limited, our study sites should not have been
      too distant to reach within almost two decades. A key explanation for the weak
      responses by macroinvertebrate communities may have been historical. When
      Fennoscandian streams were channelized for log floating, the loss of habitat
      heterogeneity was only partial. Therefore, habitat may not have been limiting the
      macroinvertebrate communities to begin with. Stream restoration to support trout
      fisheries has strong public acceptance in Finland and will likely continue to
      increase in the near future. Therefore, more effort should be placed on assessing
      restoration success from a biodiversity perspective using multiple organism
      groups in both stream and riparian ecosystems.

PMID- 21939037
TI  - River restoration success depends on the species pool of the immediate
      surroundings.
AB  - Previous studies evaluating the success of river restorations have rarely found
      any consistent effects on benthic invertebrate assemblages. In this study, we
      analyzed data from 24 river restoration projects in Germany dating back 1 to 12
      years and 1231 data sets from adjacent river reaches that lie within 0-5, 5-10,
      and 10-15 km rings centered on the restored sites. We calculated restoration
      success and recolonization potential of adjacent river reaches based on stream
      type-specific subsets of taxa indicative for good or bad habitat quality. On
      average, the restorations did not improve the benthic invertebrate community
      quality. However, we show that restoration success depends on the presence of
      source populations of desired taxa in the surrounding of restored sites. Only
      where source populations of additional desired taxa existed within a 0-5 km ring
      around the restored sites were benthic invertebrate assemblages improved by the
      restoration. Beyond the 5-km rings, this recolonization effect was no longer
      detected. We present here the first field results to support the debated argument
      that a lack of source populations in the areas surrounding restored sites may
      play an important role in the failure to establish desired invertebrate
      communities by the means of river restorations. In contrast, long-range dispersal
      of invertebrates seems to play a subordinate role in the recolonization of
      restored sites. However, because the surroundings of the restored sites were far
      from good ecological quality, the potential for improvement of restored sites was
      limited.

PMID- 21939038
TI  - Testing the field of dreams hypothesis: functional responses to urbanization and
      restoration in stream ecosystems.
AB  - As catchments become increasingly urban, the streams that drain them become
      increasingly degraded. Urban streams are typically characterized by high
      magnitude storm flows, homogeneous habitats, disconnected riparian zones, and
      elevated nitrogen concentrations. To reverse the degradation of urban water
      quality, watershed managers and regulators are increasingly turning to stream
      restoration approaches. By reshaping the channel and reconnecting the surface
      waters with their riparian zone, practitioners intend to enhance the natural
      nutrient retention capacity of the restored stream ecosystem. Despite the
      exponential growth in stream restoration projects and expenditures, there has
      been no evaluation to date of the efficacy of urban stream restoration projects
      in enhancing nitrogen retention or in altering the underlying ecosystem
      metabolism that controls instream nitrogen consumption. In this study, we
      compared ecosystem metabolism and nitrate uptake kinetics in four stream
      restoration projects within urban watersheds to ecosystem functions measured in
      four unrestored urban stream segments and four streams draining minimally
      impacted forested watersheds in central North Carolina, U.S.A. All 12 sites were
      surveyed in June through August of 2006 and again in January through March of
      2007. We anticipated that urban streams would have enhanced rates of ecosystem
      metabolism and nitrate uptake relative to forested streams due to the increases
      in nutrient loads and temperature associated with urbanization, and we predicted
      that restored streams would have further enhanced rates for these ecosystem
      functions by virtue of their increased habitat heterogeneity and water residence
      times. Contrary to our predictions we found that stream metabolism did not differ
      between stream types in either season and that nitrate uptake kinetics were not
      different between stream types in the winter. During the summer, restored stream
      reaches had substantially higher rates of nitrate uptake than unrestored or
      forested stream reaches; however, we found that variation in stream temperature
      and canopy cover explained 80% of the variation across streams in nitrate uptake.
      Because the riparian trees are removed during the first stage of natural channel
      design projects, the restored streams in this study had significantly less canopy
      cover and higher summer temperatures than the urban and forested streams with
      which they were compared.

PMID- 21939039
TI  - Assessing stream restoration effectiveness at reducing nitrogen export to
      downstream waters.
AB  - The degradation of headwater streams is common in urbanized coastal areas, and
      the role these streams play in contributing to downstream pollution is a concern
      among natural resource managers and policy makers. Thus, many urban stream
      restoration efforts are increasingly focused on reducing the downstream flux of
      pollutants. In regions that suffer from coastal eutrophication, it is unclear
      whether stream restoration does in fact reduce nitrogen (N) flux to downstream
      waters and, if so, by how much and at what cost. In this paper, we evaluate
      whether stream restoration implemented to improve water quality of urban and
      suburban streams in the Chesapeake Bay region, USA, is effective at reducing the
      export of N in stream flow to downstream waters. We assessed the effectiveness of
      restored streams positioned in the upland vs. lowland regions of Coastal Plain
      watershed during both average and stormflow conditions. We found that, during
      periods of low discharge, lowland streams that receive minor N inputs from
      groundwater or bank seepage reduced in-stream N fluxes. Furthermore, lowland
      streams with the highest N concentrations and lowest discharge were the most
      effective. During periods of high flow, only those restoration projects that
      converted lowland streams to stream-wetland complexes seemed to be effective at
      reducing N fluxes, presumably because the design promoted the spillover of stream
      flow onto adjacent floodplains and wetlands. The observed N-removal rates were
      relatively high for stream ecosystems, and on the order of 5% of the inputs to
      the watershed. The dominant forms of N entering restored reaches varied during
      low and high flows, indicating that N uptake and retention were controlled by
      distinctive processes during different hydrological conditions. Therefore, in
      order for stream restoration to effectively reduce N fluxes exported to
      downstream waters, restoration design should include features that enhance the
      processing and retention of different forms of N, and for a wide range of flow
      conditions. The use of strategic designs that match the dominant attributes of a
      stream such as position in the watershed, influence of groundwater, dominant flow
      conditions, and N concentrations is crucial to assure the success of restoration.

PMID- 21939040
TI  - River restoration success: a question of perception.
AB  - What defines success and failure of river restoration measures is a strongly
      debated topic in restoration science, but standardized approaches to evaluate
      either are still not available. The debate is usually centered on measurable
      parameters, which adhere to scientific objectivity. More subjective aspects, such
      as landscape aesthetics or recreational value, are usually left out, although
      they play an important role in the perception and communication of restoration
      success. In this paper, we show that different perceptions of restoration success
      exist by analyzing data from 26 river restoration measures in Germany. We
      addressed both objective parameters, such as hydromorphological changes and
      changes in fish and benthic invertebrate assemblages, from field investigations,
      and subjective parameters, such as opinions and perceptions, from water managers
      via an online survey. With regard to the objective hydromorphological and biotic
      parameters, our results agree with many studies that have reported improvements
      in the hydromorphology following restoration; however, there is no similar
      agreement between results concerning changes in the benthic invertebrate and fish
      assemblages. The objective results do not correspond to the subjective parameters
      because self-evaluation of the restoration projects by water managers was overly
      positive. Indeed, 40% of the respondents admitted that their evaluation was based
      on gut feeling, and only 45% of the restoration measures were monitored or
      occasionally checked. This lack of objectively recorded data meant that the water
      managers were not able to reasonably evaluate restoration success. In contrast,
      some self-evaluation responses reflected a different perception of the
      restoration success that was based on landscape aesthetic values or on benefit
      for the public; others adopted a general "condemned to success" attitude. Based
      on our data, we argue (1) that goals should be thoughtfully formulated prior to
      restoration implementation and (2) that it is necessary to monitor river
      restoration success from different perspectives.

PMID- 21939041
TI  - Ecosystem ecology meets adaptive management: food web response to a controlled
      flood on the Colorado River, Glen Canyon.
AB  - Large dams have been constructed on rivers to meet human demands for water,
      electricity, navigation, and recreation. As a consequence, flow and temperature
      regimes have been altered, strongly affecting river food webs and ecosystem
      processes. Experimental high-flow dam releases, i.e., controlled floods, have
      been implemented on the Colorado River, U.S.A., in an effort to reestablish
      pulsed flood events, redistribute sediments, improve conditions for native
      fishes, and increase understanding of how dam operations affect physical and
      biological processes. We quantified secondary production and organic matter flows
      in the food web below Glen Canyon dam for two years prior and one year after an
      experimental controlled flood in March 2008. Invertebrate biomass and secondary
      production declined significantly following the flood (total biomass, 55%
      decline; total production, 56% decline), with most of the decline driven by
      reductions in two nonnative invertebrate taxa, Potamopyrgus antipodarum and
      Gammarus lacustris. Diatoms dominated the trophic basis of invertebrate
      production before and after the controlled flood, and the largest organic matter
      flows were from diatoms to the three most productive invertebrate taxa (P.
      antipodarum, G. lacustris, and Tubificida). In contrast to invertebrates,
      production of rainbow trout (Oncorhynchus mykiss) increased substantially (194%)
      following the flood, despite the large decline in total secondary production of
      the invertebrate assemblage. This counterintuitive result is reconciled by a post
      flood increase in production and drift concentrations of select invertebrate prey
      (i.e., Chironomidae and Simuliidae) that supported a large proportion of trout
      production but had relatively low secondary production. In addition, interaction
      strengths, measured as species impact values, were strongest between rainbow
      trout and these two taxa before and after the flood, demonstrating that the
      dominant consumer-resource interactions were not necessarily congruent with the
      dominant organic matter flows. Our study illustrates the value of detailed food
      web analysis for elucidating pathways by which dam management may alter
      production and strengths of species interactions in river food webs. We suggest
      that controlled floods may increase production of nonnative rainbow trout, and
      this information can be used to help guide future dam management decisions.

PMID- 21939042
TI  - Spatial covariation between freshwater and terrestrial ecosystem services.
AB  - To inform the design and implementation of land-use policies that consider the
      variety of goods and services people derive from ecosystems, it is essential to
      understand spatial patterns of individual services, how multiple services relate
      to each other, and how these relationships vary across spatial scales and
      localities. Despite the importance of freshwater as a determinant of regional
      economic and human demographic patterns, there are surprisingly few studies that
      map the provision of a range of services associated with the quality of the
      aquatic environment. Here we examine relationships between indicators of riverine
      water and associated habitat quality, freshwater biodiversity, three terrestrial
      ecosystem services, and terrestrial biodiversity across England and Wales. The
      results indicate strong associations between our indicators of freshwater
      services. However, a comparison of these indicators of freshwater services with
      other ecosystem services (carbon storage, agricultural production, recreation)
      and biodiversity of species of conservation concern in the surrounding
      terrestrial landscape shows no clear relationships. While there are potential
      policy "win-wins" for the protection of multiple services shown by associations
      between indicators of freshwater services and carbon storage in upland areas of
      Britain, the other ecosystem services showed either negative or no relationships
      with the indicators of freshwater services. We also consider the influence that
      spatial scale has on these relationships using River Basin Districts. Our results
      indicate that relationships between indicators of services can change
      dramatically depending on the societal pressures and other regional conditions.
      Thus, the delivery of multiple ecosystem services requires the development of
      regional strategies, or of national strategies that take account of regional
      variation.

PMID- 21939043
TI  - Can forest management be used to sustain water-based ecosystem services in the
      face of climate change?
AB  - Forested watersheds, an important provider of ecosystems services related to
      water supply, can have their structure, function, and resulting streamflow
      substantially altered by land use and land cover. Using a retrospective analysis
      and synthesis of long-term climate and streamfiow data (75 years) from six
      watersheds differing in management histories we explored whether streamflow
      responded differently to variation in annual temperature and extreme
      precipitation than unmanaged watersheds. We show significant increases in
      temperature and the frequency of extreme wet and dry years since the 1980s.
      Response models explained almost all streamflow variability (adjusted R2 > 0.99).
      In all cases, changing land use altered streamflow. Observed watershed responses
      differed significantly in wet and dry extreme years in all but a stand managed as
      a coppice forest. Converting deciduous stands to pine altered the streamflow
      response to extreme annual precipitation the most; the apparent frequency of
      observed extreme wet years decreased on average by sevenfold. This increased soil
      water storage may reduce flood risk in wet years, but create conditions that
      could exacerbate drought. Forest management can potentially mitigate extreme
      annual precipitation associated with climate change; however, offsetting effects
      suggest the need for spatially explicit analyses of risk and vulnerability.

PMID- 21939044
TI  - Climate change, agricultural insecticide exposure, and risk for freshwater
      communities.
AB  - Climate change exerts direct effects on ecosystems but has additional indirect
      effects due to changes in agricultural practice. These include the increased use
      of pesticides, changes in the areas that are cultivated, and changes in the crops
      cultivated. It is well known that pesticides, and in particular insecticides,
      affect aquatic ecosystems adversely. To implement effective mitigation measures
      it is necessary to identify areas that are affected currently and those that will
      be affected in the future. As a consequence, we predicted potential exposure to
      insecticide (insecticide runoff potential, RP) under current conditions (1990)
      and under a model scenario of future climate and land use (2090) using a
      spatially explicit model on a continental scale, with a focus on Europe. Space
      for-time substitution was used to predict future levels of insecticide
      application, intensity of agricultural land use, and cultivated crops. To assess
      the indirect effects of climate change, evaluation of the risk of insecticide
      exposure was based on a trait-based, climate-insensitive indicator system (SPEAR,
      SPEcies At Risk). To this end, RP and landscape characteristics that are relevant
      for the recovery of affected populations were combined to estimate the ecological
      risk (ER) of insecticides for freshwater communities. We predicted a strong
      increase in the application of, and aquatic exposure to, insecticides under the
      future scenario, especially in central and northern Europe. This, in turn, will
      result in a severe increase in ER in these regions. Hence, the proportion of
      stream sites adjacent to arable land that do not meet the requirements for good
      ecological status as defined by the EU Water Framework Directive will increase
      (from 33% to 39% for the EU-25 countries), in particular in the Scandinavian and
      Baltic countries (from 6% to 19%). Such spatially explicit mapping of risk
      enables the planning of adaptation and mitigation strategies including vegetated
      buffer strips and nonagricultural recolonization zones along streams.

PMID- 21939045
TI  - Terrestrial organic matter as subsidies that aid in the recovery of
      macroinvertebrates in industrially damaged lakes.
AB  - The importance of allochthonous carbon to the productivity of stream ecosystems
      in temperate ecozones is well understood, but this relationship is less
      established in oligotrophic lakes. The nearshore littoral zones, at the interface
      of terrestrial and aquatic systems, are areas where the influence of terrestrial
      subsidies is likely greatest. We investigated the response of nearshore
      communities to variation in the quantity and composition of allochthonous
      materials, determined the landscape characteristics that regulate the variation
      of this subsidy, and explored the potential for terrestrial restoration practices
      to influence the export of organic matter to lakes. Stepwise multiple regressions
      revealed that diversity of nearshore macroinvertebrate families increased with
      the amount of fine particulate organic matter (FPOM) captured in sediment traps.
      The quantity of FPOM (g) increased with forest cover, and the relative amount of
      FPOM (percentage of total particulate material) in the traps increased with
      surface area of wetland in the catchments. These models suggest that
      terrestrially derived subsidies are important in smelter-impacted watersheds, and
      that the restoration of forests and wetlands will speed the return of nearshore
      consumer community diversity in industrially damaged lakes.

PMID- 21939046
TI  - Remote analysis of biological invasion and the impact of enemy release.
AB  - Escape from natural enemies is a widely held generalization for the success of
      exotic plants. We conducted a large-scale experiment in Hawaii (USA) to quantify
      impacts of ungulate removal on plant growth and performance, and to test whether
      elimination of an exotic generalist herbivore facilitated exotic success.
      Assessment of impacted and control sites before and after ungulate exclusion
      using airborne imaging spectroscopy and LiDAR, time series satellite
      observations, and ground-based field studies over nine years indicated that
      removal of generalist herbivores facilitated exotic success, but the abundance of
      native species was unchanged. Vegetation cover <1 m in height increased in
      ungulate-free areas from 48.7% +/- 1.5% to 74.3% +/- 1.8% over 8.4 years,
      corresponding to an annualized growth rate of lambda = 1.05 +/- 0.01 yr(-1)
      (median +/- SD). Most of the change was attributable to exotic plant species,
      which increased from 24.4% +/- 1.4% to 49.1% +/- 2.0%, (lambda = 1.08 +/- 0.01
      yr(-1)). Native plants experienced no significant change in cover (23.0% +/- 1.3%
      to 24.2% +/- 1.8%, lambda = 1.01 +/- 0.01 yr(-1)). Time series of satellite
      phenology were indistinguishable between the treatment and a 3.0-km2 control site
      for four years prior to ungulate removal, but they diverged immediately following
      exclusion of ungulates. Comparison of monthly EVI means before and after ungulate
      exclusion and between the managed and control areas indicates that EVI strongly
      increased in the managed area after ungulate exclusion. Field studies and
      airborne analyses show that the dominant invader was Senecio madagascariensis, an
      invasive annual forb that increased from < 0.01% to 14.7% fractional cover in
      ungulate-free areas (lambda = 1.89 +/- 0.34 yr(-1)), but which was nearly absent
      from the control site. A combination of canopy LAI, water, and fractional cover
      were expressed in satellite EVI time series and indicate that the invaded region
      maintained greenness during drought conditions. These findings demonstrate that
      enemy release from generalist herbivores can facilitate exotic success and
      suggest a plausible mechanism by which invasion occurred. They also show how
      novel remote-sensing technology can be integrated with conservation and
      management to help address exotic plant invasions.

PMID- 21939047
TI  - Long-term dynamics of biotic and abiotic resistance to exotic species invasion in
      restored vernal pool plant communities.
AB  - Invasion of native ecosystems by exotic species can seriously threaten native
      biodiversity, alter ecosystem function, and inhibit conservation. Moreover,
      restoration of native plant communities is often impeded by competition from
      exotic species. Exotic species invasion may be limited by unfavorable abiotic
      conditions and by competition with native species, but the relative importance of
      biotic and abiotic factors remains controversial and may vary during the invasion
      process. We used a long-term experiment involving restored vernal pool plant
      communities to characterize the temporal dynamics of exotic species invasion, and
      to evaluate the relative support for biotic and abiotic factors affecting
      invasion resistance. Experimental pools (n=256) were divided among controls and
      several seeding treatments. In most treatments, native vernal pool species were
      initially more abundant than exotic species, and pools that initially received
      more native seeds exhibited lower frequencies of exotic species over time.
      However, even densely seeded pools were eventually dominated by exotic species,
      following extreme climatic events that reduced both native and exotic plant
      densities across the study site. By the sixth year of the experiment, most pools
      supported more exotics than native vernal pool species, regardless of seeding
      treatment or pool depth. Although deeper pools were less invaded by exotic
      species, two exotics (Hordeum marinum and Lolium multiflorum) were able to
      colonize deeper pools as soon as the cover of native species was reduced by
      climatic extremes. Based on an information-theoretic analysis, the best model of
      invasion resistance included a nonlinear effect of seeding treatment and both
      linear and nonlinear effects of pool depth. Pool depth received more support as a
      predictor of invasion resistance, but seeding intensity was also strongly
      supported in multivariate models of invasion, and was the best predictor of
      resistance to invasion by H. marinum and L. multilorum. We conclude that extreme
      climatic events can facilitate exotic species invasions by both reducing abiotic
      constraints and weakening biotic resistance to invasion.

PMID- 21939048
TI  - Can spatial isolation help predict dispersal-limited sites for native species
      restoration?
AB  - When the distribution of species is limited by propagule supply, new populations
      may be initiated by seed addition, but identifying suitable sites for efficiently
      targeted seed addition remains a major challenge for restoration. In addition to
      the biotic or abiotic variables typically used in species distribution models,
      spatial isolation from conspecifics could help predict the suitability of
      unoccupied sites. Site suitability might be expected to increase with spatial
      isolation after other factors are accounted for, since isolation increases the
      chance that a site is unoccupied only because of propagule limitation. For two
      native annual forbs in Californian grasslands, we combined experimental seeding
      and niche modeling to ask whether suitability of unoccupied sites could be
      predicted by spatial variables (either distances from, or densities of,
      conspecific populations), either by themselves or in combination with niche
      models. We also asked whether experimental tests of these predictions held up not
      only in the short term (one year), but also in the longer term (three years). For
      Lasthenia californica, seed additions were only successful relatively near
      existing populations. For Lupinus nanus, seeding success was low and was
      positively related to the number of conspecifics within 1 km. For both species, a
      few previously unoccupied sites remained occupied three years after seeding, but
      this subset was not predictable based on either spatial or niche variables. Seed
      addition alone may be a limited means of native forb restoration if suitable
      unoccupied sites are either rare or unpredictable, or if they tend to be close to
      where the species already occurs.

PMID- 21939049
TI  - Provenance, life span, and phylogeny do not affect grass species' responses to
      nitrogen and phosphorus.
AB  - Successful conservation management requires an understanding of how species
      respond to intervention. Native and exotic species may respond differently to
      management interventions due to differences arising directly from their origin
      (i.e., provenance) or indirectly due to biased representations of different life
      history types (e.g., annual vs. perennial life span) or phylogenetic lineages
      among provenance (i.e., native or exotic origin) groups. Thus, selection of a
      successful management regime requires knowledge of the life history and
      provenance-bias in the local flora and an understanding of the interplay between
      species characteristics across existing environmental gradients in the landscape.
      Here we tested whether provenance, phylogeny, and life span interact to determine
      species distributions along natural gradients of soil chemistry (e.g., soil
      nitrogen and phosphorus) in 10 upland prairie sites along a 600-km latitudinal
      transect running from southern Vancouver Island in British Columbia, Canada, to
      the Willamette Valley in Oregon, USA. We found that soil nitrate, phosphorus, and
      pH exerted strong control over community composition. However, species
      distributions along environmental gradients were unrelated to provenance, life
      span, or phylogenetic groupings. We then used a greenhouse experiment to more
      precisely measure the response of common grass species to nitrogen and phosphorus
      supply. As with the field data, species responses to nutrient additions did not
      vary as a function of provenance, life span, or phylogeny. Native and exotic
      species differed strongly in the relationship between greenhouse-measured
      tolerance of low nutrients and field abundance. Native species with the greatest
      ability to maintain biomass production at low nutrient supply rates were most
      abundant in field surveys, as predicted by resource competition theory. In
      contrast, there was no relationship between exotic-species biomass at low
      nutrient levels and field abundance. The implications of these findings for
      management of invasive species are substantial in that they overturn a general
      belief that reduction of nutrient supplies favors native species. The
      idiosyncratic nature of species response to nutrients in this study suggests that
      manipulation of nutrient supplies is unlikely to alter the overall balance
      between native and exotic species, although it may well be useful to control
      specific exotic species.

PMID- 21939050
TI  - Diversity-function relationships changed in a long-term restoration experiment.
AB  - The central tenet of biodiversity-ecosystem function (BEF) theory, that species
      richness increases function, could motivate restoration practitioners to
      incorporate a greater number of species into their projects. But it is not yet
      clear how well BEF theory predicts outcomes of restoration, because it has been
      developed through tests involving short-run and tightly controlled (e.g., weeded)
      experiments. Thus, we resampled our 1997 BEF experiment in a restored salt marsh
      to test for long-term effects of species richness (plantings with 1, 3, and 6
      species per 2 x 2 m plot), with multiple ecosystem functions as response
      variables. Over 11 years, 1- and 6-species assemblages converged on intermediate
      richness (mean = 3.9 species/ 0.25-m2 plot), and composition changed nonrandomly
      throughout the site. While three species became rare, the two most productive
      species became co-dominant. The two dominants controlled and increased shoot
      biomass, which appeared to decrease species richness. Diversity-function
      relationships became less positive over 11 years and differed significantly with
      (a) the species-richness metric (planted vs. measured), and (b) the indicator of
      function (shoot biomass, height, and canopy layering). The loss of positive
      relationships between species richness and function in our restored site began
      soon after we stopped weeding and continued with increasing dominance by
      productive species. Where species-rich plantings are unlikely to ensure long-term
      restoration of functions, as in our salt marsh, we recommend dual efforts to
      establish (1) dominant species that provide high levels of target functions, and
      (2) subordinate species, which might provide additional functions under current
      or future conditions.

PMID- 21939051
TI  - Use of computed tomography imaging for quantifying coarse roots, rhizomes, peat,
      and particle densities in marsh soils.
AB  - Computed tomography (CT) imaging has been used to describe and quantify subtidal,
      benthic animals such as polychaetes, amphipods, and shrimp. Here, for the first
      time, CT imaging is used to quantify wet mass of coarse roots, rhizomes, and peat
      in cores collected from organic-rich (Jamaica Bay, New York) and mineral (North
      Inlet, South Carolina) Spartina alterniflora soils. Image analysis software was
      coupled with the CT images to measure abundance and diameter of the coarse roots
      and rhizomes in marsh soils. Previously, examination of marsh roots and rhizomes
      was limited to various hand-sieving methods that were often time-consuming,
      tedious, and error prone. CT imaging can discern the coarse roots, rhizomes, and
      peat based on their varying particle densities. Calibration rods composed of
      materials with standard densities (i.e., air, water, colloidal silica, and glass)
      were used to operationally define the specific x-ray attenuations of the coarse
      roots, rhizomes, and peat in the marsh cores. Significant regression
      relationships were found between the CT-determined wet mass of the coarse roots
      and rhizomes and the hand-sieved dry mass of the coarse roots and rhizomes in
      both the organic-rich and mineral marsh soils. There was also a significant
      relationship between the soil percentage organic matter and the CT-determined
      peat particle density among organic-rich and mineral soils. In only the mineral
      soils, there was a significant relationship between the soil percentage organic
      matter and the CT-determined peat wet mass. Using CT imaging, significant
      positive nitrogen fertilization effects on the wet masses of the coarse roots,
      rhizomes, and peat, and the abundance and diameter of rhizomes were measured in
      the mineral soils. In contrast, a deteriorating salt marsh island in Jamaica Bay
      had significantly less mass of coarse roots and rhizomes at depth (10-20 cm), and
      a significantly lower abundance of roots and rhizomes compared with a stable
      marsh. However, the diameters of the rhizomes in the deteriorating marsh were
      significantly greater than in the stable marsh. CT imaging is a rapid approach to
      quantify coarse roots, rhizomes, peat, and soil particle densities in coastal
      wetlands, but the method is unable at this time to quantify fine roots.

PMID- 21939052
TI  - Benthic diversity gradients and shifting baselines: implications for assessing
      environmental status.
AB  - The increasing pressure on marine biodiversity emphasizes the importance of
      finding benchmarks against which to assess change. This is, however, a
      notoriously difficult task in estuarine ecosystems, where environmental gradients
      are steep, and where benthic biodiversity is highly variable in space and time.
      Although recent emphasis on diverse, healthy benthic communities in legislative
      frameworks has increased the number of indices developed for assessing benthic
      status, there is a lack of quantitative baselines in benthic diversity that would
      enable comparisons across broad spatial scales, encompassing different
      environmental settings and bioregions. By taking advantage of long-term
      monitoring data, spanning hundreds of stations over the past 40 years, we provide
      a comprehensive analysis of benthic a, beta, and gamma diversity, encompassing
      the entire' salinity gradient of the open sea areas of the large, brackish-water
      Baltic Sea. Using a relatively simple measure, average regional diversity, we
      define area-specific reference conditions and acceptable deviation against which
      to gauge current conditions in benthic macrofaunal diversity. Results show a
      severely impaired condition throughout large areas of the Baltic for the
      assessment period 2001-2006. All ecosystems are plagued by baselines that shift
      in time and space, and their definition is not trivial, but average regional
      diversity may offer a transparent way to deal with such changes in low-diversity
      systems. Identifying baselines will be of increasing importance given the
      potential of climatic drivers to interact with local anthropogenic stressors to
      affect patterns of biodiversity. Our analysis provides an evaluation of the
      current condition in a system that has been heavily influenced by anthropogenic
      impact and changing oceanographic conditions, and it provides a basis for future
      impact assessment and ecosystem-based management.

PMID- 21939053
TI  - The relationship between agricultural intensification and biological control:
      experimental tests across Europe.
AB  - Agricultural intensification can affect biodiversity and related ecosystem
      services such as biological control, but large-scale experimental evidence is
      missing. We examined aphid pest populations in cereal fields under experimentally
      reduced densities of (1) ground-dwelling predators (-G), (2) vegetation-dwelling
      predators and parasitoids (-V), (3) a combination of (1) and (2) (-G-V), compared
      with open-fields (control), in contrasting landscapes with low vs. high levels of
      agricultural intensification (AI), and in five European regions. Aphid
      populations were 28%, 97%, and 199% higher in -G, -V, and -G-V treatments,
      respectively, compared to the open fields, indicating synergistic effects of both
      natural-enemy groups. Enhanced parasitoid: host and predator: prey ratios were
      related to reduced aphid population density and population growth. The relative
      importance of parasitoids and vegetation-dwelling predators greatly differed
      among European regions, and agricultural intensification affected biological
      control and aphid density only in some regions. This shows a changing role of
      species group identity in diverse enemy communities and a need to consider region
      specific landscape management.

PMID- 21939054
TI  - Two-dimensional wavelet analysis of spruce budworm host basal area in the Border
      Lakes landscape.
AB  - Increases in the extent and severity of spruce budworm (Choristoneura fumiferana
      Clem.) outbreaks over the last century are thought to be the result of changes in
      forest structure due to forest management. A corollary of this hypothesis is that
      manipulations of forest structure and composition can be used to reduce future
      forest vulnerability. However, to what extent historical forest management has
      influenced current spatial patterns of spruce budworm host species is unknown. To
      identify landscape-scale spatial legacies of forest management in patterns of
      spruce budworm host species (i.e., Abies balsamea and Picea spp.), we analyzed
      remotely sensed forest data from the Border Lakes landscape of northern Minnesota
      and northwestern Ontario. Our study area contains three regions with different
      management histories: (1) fine-scale logging patterns in Minnesota, (2) coarse
      scale logging patterns in Ontario, and (3) very limited logging history in the
      Boundary Waters Canoe Area and adjacent Quetico Provincial Park. We analyzed
      forest basal-area data using wavelets and null models to identify: (1) at which
      scales forest basal area is structured, (2) where those scales of pattern are
      significantly present, and (3) whether regions of local significance correspond
      to regional boundaries that separate the study area. Results indicate that
      spatial patterns in host basal area are created by nonstationary processes and
      that these processes are further constrained by lakes and wetlands. Wavelet
      analysis combined with significance testing revealed a bimodal distribution of
      scale-specific wavelet variance and separate zones of host species basal area
      that partially correspond with regional boundaries, particularly between
      Minnesota and the Wilderness region. This research represents one of the first
      comparisons of forest spatial structure in this region across an international
      border and presents a novel method of two-dimensional wavelet analysis that can
      be used to identify significant scale-specific structure in spatial data.

PMID- 21939055
TI  - Fire history and tree recruitment in the Colorado Front Range upper montane zone:
      implications for forest restoration.
AB  - Forests experiencing moderate- or mixed-severity fire regimes are presumed to be
      widespread across the western United States, but few studies have characterized
      these complex disturbance regimes and their effects on contemporary forest
      structure. Restoration of pre-fire-suppression open-forest structure to reduce
      the risk of uncharacteristic stand-replacing fires is a guiding principle in
      forest management policy, but identifying which forests are clear candidates for
      restoration remains a challenge. We conducted dendroecological reconstructions of
      fire history and stand structure at 40 sites in the upper montane zone of the
      Colorado Front Range (2400-2800 m), sampled in proportion to the distribution of
      forest types in that zone (50% dominated by ponderosa pine, 28% by lodgepole
      pine, 12% by aspen, 10% by Douglas-fir). We characterized past fire severity
      based on remnant criteria at each site in order to assess the effect of fire
      history on tree establishment patterns, and we also evaluated the influence of
      fire suppression and climate. We found that 62% of the sites experienced
      predominantly moderate-severity fire, 38% burned at high severity, and no sites
      burned exclusively at low severity. The proportion of total tree and sapling
      establishment was significantly different among equal time periods based on a chi
      square test, with highest tree and sapling establishment during the pre-fire
      suppression period (1835-1919). Superposed epoch analysis revealed that fires
      burned during years of extreme drought (95% CI). The major pulse of tree
      establishment in the upper montane zone occurred during a multidecadal period of
      extreme drought conditions in the Colorado Front Range (1850-1889), during which
      53% of the fires from the 1750-1989 period burned. In the upper montane zone of
      the Colorado Front Range, historical evidence suggests that these forests are
      resilient to prolonged periods of severe drought and associated severe fires.

PMID- 21939056
TI  - Coral identity underpins architectural complexity on Caribbean reefs.
AB  - The architectural complexity of ecosystems can greatly influence their capacity
      to support biodiversity and deliver ecosystem services. Understanding the
      components underlying this complexity can aid the development of effective
      strategies for ecosystem conservation. Caribbean coral reefs support and protect
      millions of livelihoods, but recent anthropogenic change is shifting communities
      toward reefs dominated by stress-resistant coral species, which are often less
      architecturally complex. With the regionwide decline in reef fish abundance, it
      is becoming increasingly important to understand changes in coral reef community
      structure and function. We quantify the influence of coral composition,
      diversity, and morpho-functional traits on the architectural complexity of reefs
      across 91 sites at Cozumel, Mexico. Although reef architectural complexity
      increases with coral cover and species richness, it is highest on sites that are
      low in taxonomic evenness and dominated by morpho-functionally important, reef
      building coral genera, particularly Montastraea. Sites with similar coral
      community composition also tend to occur on reefs with very similar architectural
      complexity, suggesting that reef structure tends to be determined by the same key
      species across sites. Our findings provide support for prioritizing and
      protecting particular reef types, especially those dominated by key reef-building
      corals, in order to enhance reef complexity.

PMID- 21939057
TI  - A Bayesian approach for understanding the role of ship speed in whale-ship
      encounters.
AB  - Mandatory or voluntary reductions in ship speed are a common management strategy
      for reducing deleterious encounters between large ships and large whales. This
      has produced strong resistance from shipping and marine transportation entities,
      in part because very few studies have empirically demonstrated whether or to what
      degree ship speed influences ship-whale encounters. Here we present the results
      of four years of humpback whale sightings made by observers aboard cruise ships
      in Alaska, representing 380 cruises and 891 ship-whale encounters. Encounters
      occurred at distances from 21 m to 1000 m (x = 567 m) with 61 encounters (7%)
      occurring between 200 m and 100 m, and 19 encounters (2%) within 100 m.
      Encounters were spatially aggregated and highly variable across all ship speeds.
      Nevertheless a Bayesian change-point model found that the relationship between
      whale distance and ship speed changed at 11.8 knots (6.1 m/s) with whales
      encountering ships, on average, 114 m closer when ship speeds were above 11.8
      knots. Binning encounter distances by 1-knot speed increments revealed a clear
      decrease in encounter distance with increasing ship speed over the range of 7-17
      knots (3.6-8.7 m/s). Our results are the first to demonstrate that speed
      influences the encounter distance between large ships and large whales. Assuming
      that the closer ships come to whales the more likely they are to be struck, our
      results suggest that reduced ship speed may be an effective management action in
      reducing the probability of a collision.

PMID- 21939058
TI  - Where the wild things are: predicting hotspots of seabird aggregations in the
      California Current System.
AB  - Marine protected areas (MPAs) provide an important tool for conservation of
      marine ecosystems. To be most effective, these areas should be strategically
      located in a manner that supports ecosystem function. To inform marine spatial
      planning and support strategic establishment of MPAs within the California
      Current System, we identified areas predicted to support multispecies
      aggregations of seabirds ("hotspots"). We developed habitat-association models
      for 16 species using information from at-sea observations collected over an 11
      year period (1997-2008), bathymetric data, and remotely sensed oceanographic data
      for an area from north of Vancouver Island, Canada, to the USA/Mexico border and
      seaward 600 km from the coast. This approach enabled us to predict distribution
      and abundance of seabirds even in areas of few or no surveys. We developed single
      species predictive models using a machine-learning algorithm: bagged decision
      trees. Single-species predictions were then combined to identify potential
      hotspots of seabird aggregation, using three criteria: (1) overall abundance
      among species, (2) importance of specific areas ("core areas") to individual
      species, and (3) predicted persistence of hotspots across years. Model
      predictions were applied to the entire California Current for four seasons
      (represented by February, May, July, and October) in each of 11 years. Overall,
      bathymetric variables were often important predictive variables, whereas
      oceanographic variables derived from remotely sensed data were generally less
      important. Predicted hotspots often aligned with currently protected areas (e.g.,
      National Marine Sanctuaries), but we also identified potential hotspots in
      Northern California/Southern Oregon (from Cape Mendocino to Heceta Bank),
      Southern California (adjacent to the Channel Islands), and adjacent to Vancouver
      Island, British Columbia, that are not currently included in protected areas.
      Prioritization and identification of multispecies hotspots will depend on which
      group of species is of highest management priority. Modeling hotspots at a broad
      spatial scale can contribute to MPA site selection, particularly if complemented
      by fine-scale information for focal areas.

PMID- 21939059
TI  - Migration path annotation: cross-continental study of migration-flight response
      to environmental conditions.
AB  - Understanding the movements of animals is pivotal for understanding their ecology
      and predicting their survival in the face of rapid global changes to climate,
      land use, and habitats, thus facilitating more effective habitat management.
      Migration by flying animals is an extreme form of movement that may be especially
      influenced by weather. With satellite telemetry studies, and the growing
      availability of information about the Earth's weather and land surface
      conditions, many data are collected that can advance our understanding about the
      mechanisms that shape migrations. We present the track annotation approach for
      movement data analysis using information about weather from the North American
      Reanalysis data set, a publicly available, regional, high-resolution model
      observation hybrid product, and about topography, from a publicly available high
      resolution digital elevation model (DEM). As a case study, we present the
      analysis of the response to environmental conditions in three contrasting
      populations of Turkey Vultures (Cathartes aura) across North America, tracked
      with a three-dimensional GPS-based sensor. Two populations in the east and west
      coasts of the United States responded similarly to weather, indicating use of
      both slope and thermal soaring. Continental-interior, "Plains populations,"
      exhibited a different migratory pattern primarily indicative of thermal soaring.
      These differences help us understand the constraints and behaviors of soaring
      migrants. The track annotation approach allowed large-scale comparative study of
      movement in an important migratory species, and will enable similar studies at
      local to global scales.

PMID- 21939060
TI  - Comparison of statistical and theoretical habitat models for conservation
      planning: the benefit of ensemble prediction.
AB  - Selection of a modeling approach is an important step in the conservation
      planning process, but little guidance is available. We compared two statistical
      and three theoretical habitat modeling approaches representing those currently
      being used for avian conservation planning at landscape and regional scales:
      hierarchical spatial count (HSC), classification and regression tree (CRT),
      habitat suitability index (HSI), forest structure database (FS), and habitat
      association database (HA). We focused our comparison on models for five priority
      forest-breeding species in the Central Hardwoods Bird Conservation Region:
      Acadian Flycatcher, Cerulean Warbler, Prairie Warbler, Red-headed Woodpecker, and
      Worm-eating Warbler. Lacking complete knowledge on the distribution and abundance
      of each species with which we could illuminate differences between approaches and
      provide strong grounds for recommending one approach over another, we used two
      approaches to compare models: rank correlations among model outputs and
      comparison of spatial correspondence. In general, rank correlations were
      significantly positive among models for each species, indicating general
      agreement among the models. Worm-eating Warblers had the highest pairwise
      correlations, all of which were significant (P < 0.05). Red-headed Woodpeckers
      had the lowest agreement among models, suggesting greater uncertainty in the
      relative conservation value of areas within the region. We assessed model
      uncertainty by mapping the spatial congruence in priorities (i.e., top ranks)
      resulting from each model for each species and calculating the coefficient of
      variation across model ranks for each location. This allowed identification of
      areas more likely to be good targets of conservation effort for a species, those
      areas that were least likely, and those in between where uncertainty is higher
      and thus conservation action incorporates more risk. Based on our results, models
      developed independently for the same purpose (conservation planning for a
      particular species in a particular geography) yield different answers and thus
      different conservation strategies. We assert that using only one habitat model
      (even if validated) as the foundation of a conservation plan is risky. Using
      multiple models (i.e., ensemble prediction) can reduce uncertainty and increase
      efficacy of conservation action when models corroborate one another and increase
      understanding of the system when they do not.

PMID- 21939061
TI  - Songbird response to increased willow (Salix spp.) growth in Yellowstone's
      northern range.
AB  - After nearly a century of height suppression, willows (Salix spp.) in the
      northern range of Yellowstone National Park, U.S.A., are increasing in height
      growth as a possible consequence of wolf (Canis lupus) restoration, climate
      change, or other factors. Regardless of the drivers, the recent release of this
      rare but important habitat type could have significant implications for
      associated songbirds that are exhibiting declines in the region. Our objective
      was to evaluate bird response to releasing willows by comparing willow structure
      and bird community composition across three willow growth conditions: height
      suppressed, recently released, and previously tall (i.e., tall prior to the
      height increase of released willows). Released and previously tall willows
      exhibited high and similar vertical structure, but released willows were
      significantly lower in horizontal structure. Suppressed willows were
      significantly shorter and lower in horizontal cover than released or previously
      tall willows. Bird richness increased along a gradient from lowest in suppressed
      to highest in previously tall willows, but abundance and diversity were similar
      between released and previously tall willows, despite lower horizontal cover in
      the released condition. Common Yellowthroat (Geothlypis trichas) and Lincoln's
      Sparrow (Melospiza lincolnii) were found in all three growth conditions; however,
      Yellow Warbler (Dendroica petechia), Warbling Vireo (Vireo gilvus), Willow
      Flycatcher (Empidonax traillii), and Song Sparrow (Melospiza melodii) were
      present in released and previously tall willows only. Wilson's Warbler (Wilsonia
      pusilla) was found in previously tall willows only, appearing to specialize on
      tall, dense willows. The results of our a priori habitat models indicated that
      foliage height diversity was the primary driver of bird richness, abundance, and
      diversity. These results indicate that vertical structure was a more important
      driver of bird community variables than horizontal structure and that riparian
      and willow-dependent bird species have responded positively to increased willow
      growth in the region.

PMID- 21939062
TI  - Do birds and beetles show similar responses to urbanization?
AB  - To date, the vast majority of studies in urban areas have been carried out on
      birds, yet it is not known whether the responses of birds to urbanization are
      congruent with those of other taxa. In this paper, we compared the responses of
      breeding birds and carabid beetles to urbanization, specifically asking whether
      the emerging generalizations of the effects of extreme levels of urbanization on
      birds (declines in total species richness and the richness of specialist species,
      increases in total abundance and the abundances of native generalist and
      introduced species, and community simplification, including increasing
      similarity) could also be applied to ground beetles. We also directly tested for
      congruence between birds and ground beetles using correlations between variables
      describing bird and beetle community structure and correlations between bird and
      beetle distance matrices describing community dissimilarity between pairs of
      sampling locations. Breeding bird and carabid beetle community data were
      collected in Ottawa, Ontario, and Gatineau, Quebec, Canada, in two groups of
      sites: developed sites representing the predictor variable within-site housing
      density, and forested sites adjacent to development representing the predictor
      variable neighboring housing density (each site was 0.25 km2). Breeding birds and
      carabid beetles do not respond similarly to increasing within-site housing
      density but do exhibit some similar responses to increasing neighboring housing
      density. Birds displayed strong declines in diversity, compositional changes, and
      community simplification in response to increasing within-site housing density.
      Forest and introduced species of birds and beetles responded similarly to
      increasing housing density within a site, but responses of overall diversity and
      open-habitat species richness and patterns of community simplification differed
      between birds and beetles. Increasing neighboring housing density resulted in
      increases in the abundances of introduced birds and introduced beetles and
      similar patterns of community simplification in both taxa. To better understand
      and mitigate the effects of urbanization on biodiversity, we suggest that, in
      addition to the responses of birds, future research should focus on the responses
      of other taxa in the urban matrix.

PMID- 21939063
TI  - The accuracy of climate models' simulated season lengths and the effectiveness of
      grid scale correction factors.
AB  - Global climate change is expected to impact biological populations through a
      variety of mechanisms including increases in the length of their growing season.
      Climate models are useful tools for predicting how season length might change in
      the future. However, the accuracy of these models tends to be rather low at
      regional geographic scales. Here, I determined the ability of several atmosphere
      and ocean general circulating models (AOGCMs) to accurately simulate historical
      season lengths for a temperate ectotherm across the continental United States. I
      also evaluated the effectiveness of regional-scale correction factors to improve
      the accuracy of these models. I found that both the accuracy of simulated season
      lengths and the effectiveness of the correction factors to improve the model's
      accuracy varied geographically and across models. These results suggest that
      regional specific correction factors do not always adequately remove potential
      discrepancies between simulated and historically observed environmental
      parameters. As such, an explicit evaluation of the correction factors'
      effectiveness should be included in future studies of global climate change's
      impact on biological populations.

PMID- 21939064
TI  - The relative influence of habitat loss and fragmentation: do tropical mammals
      meet the temperate paradigm?
AB  - The relative influence of habitat loss vs. habitat fragmentation per se (the
      breaking apart of habitat) on species distribution and abundance is a topic of
      debate. Although some theoretical studies predict a strong negative effect of
      fragmentation, consensus from empirical studies is that habitat fragmentation has
      weak effects compared with habitat loss and that these effects are as likely to
      be positive as negative. However, few empirical investigations of this issue have
      been conducted on tropical or wide-ranging species that may be strongly
      influenced by changes in patch size and edge that occur with increasing
      fragmentation. We tested the relative influence of habitat loss and fragmentation
      by examining occupancy of forest patches by 20 mid- and large-sized Neotropical
      mammal species in a fragmented landscape of northern Guatemala. We related patch
      occupancy of mammals to measures of habitat loss and fragmentation and compared
      the influence of these two factors while controlling for patch-level variables.
      Species responded strongly to both fragmentation and loss, and response to
      fragmentation generally was negative. Our findings support previous assumptions
      that conservation of large mammals in the tropics will require conservation
      strategies that go beyond prevention of habitat loss to also consider forest
      cohesion or other aspects of landscape configuration.

PMID- 21939065
TI  - Subpopulation structure of caribou (Rangifer tarandus L.) in arctic and subarctic
      Canada.
AB  - Effective management and conservation of species, subspecies, or ecotypes require
      an understanding of how populations are structured in space. We used satellite
      tracking locations and hierarchical and fuzzy clustering to quantify
      subpopulations within the behaviorally different barren-ground caribou (Rangifer
      tarandus groenlandicus), Dolphin and Union island caribou (R. t. groenlandicus x
      pearyi), and boreal (R. t. caribou) caribou ecotypes in the Northwest Territories
      and Nunavut, Canada. Using a novel approach, we verified that the previously
      recognized Cape Bathurst, Bluenose-West, Bluenose-East, Bathurst, Beverly,
      Qamanirjuaq, and Lorillard barren-ground subpopulations were robust and that the
      Queen Maude Gulf and Wager Bay barren-ground subpopulations were organized as
      individuals. Dolphin and Union island and boreal caribou formed one and two
      distinct subpopulation, respectively, and were organized as individuals. Robust
      subpopulations were structured by strong annual spatial affiliation among
      females; subpopulations organized as individuals were structured by migratory
      connectivity, barriers to movement, and/or habitat discontinuity. One barren
      ground subpopulation used two calving grounds, and one calving ground was used by
      two barren-ground subpopulations, indicating that these caribou cannot be
      reliably assigned to subpopulations solely by calving-ground use. They should be
      classified by annual spatial affiliation among females. Annual-range size and
      path lengths varied significantly among ecotypes, including mountain woodland
      caribou (R. t. caribou), and reflected behavioral differences. An east-west cline
      in annual-range sizes and path lengths among migratory barren-ground
      subpopulations likely reflected differences in subpopulation size and habitat
      conditions and further supported the subpopulation structure identified.

PMID- 21939066
TI  - Environmental impact propagated by cross-system subsidy: chronic stream pollution
      controls riparian spider populations.
AB  - Resource subsidies between habitats are common and create the potential for the
      propagation of environmental impacts across system boundaries. However, recent
      understanding of the potential for subsidy-mediated cross-system impact
      propagations is limited and primarily based on passive flows of nutrients and
      detritus or short-term effects. Here, we assess the effects of sustained
      alterations in aquatic insect emergence (active subsidy pathway), due to chronic
      stream pollution, for riparian spiders. The sustained reduction in aquatic insect
      densities at the polluted reaches resulted in a marked decline in web spider
      population density and a shift in spider community composition. Our results
      provide the first evidence that stream pollution can control populations and
      community structure of terrestrial predators via sustained alterations in aquatic
      subsidies, emphasizing the role of subtle trophic linkages in the transmission of
      environmental impacts across ecosystem boundaries.

PMID- 21939067
TI  - Much ado about nothings: using zero similarity points in distance-decay curves.
AB  - Distance decay is used to describe the (usually exponential) decay in ecological
      similarity of assemblages between two sites as a function of their distance apart
      along an environmental gradient. Exponential distance-decay curves are routinely
      fitted by calculating the ecological similarity between each pair of sites, and
      fitting a linear regression to the points on a scatter plot of log-similarity vs.
      distance (x-axis). However, pairs of sites where the assemblages have no species
      in common pose a problem, because the similarity is zero, and the log
      transformation cannot be applied. Common fixes to this problem (i.e., either
      removing or transforming the zero values) are shown to have undesirable
      consequences and to give widely disparate estimates. A new method is presented as
      a special case of a generalized dissimilarity model. It is fitted very quickly
      and easily using existing software, and it does not require removal or
      transformation of the zero similarity points. Its simplicity makes it convenient
      for use in conjunction with the resampling methods that are routinely employed to
      test hypotheses, to obtain standard errors of estimated parameters, or to compare
      distance-decay curves. A word of caution about standard application of the
      bootstrap is noted, and modified bootstrap and jackknife alternatives are
      demonstrated.

PMID- 21939068
TI  - Spatial patterns reveal negative density dependence and habitat associations in
      tropical trees.
AB  - Understanding how plant species coexist in tropical rainforests is one of the
      biggest challenges in community ecology. One prominent hypothesis suggests that
      rare species are at an advantage because trees have lower survival in areas of
      high conspecific density due to increased attack by natural enemies, a process
      known as negative density dependence (NDD). A consensus is emerging that NDD is
      important for plant-species coexistence in tropical forests. Most evidence comes
      from short-term studies, but testing the prediction that NDD decreases the
      spatial aggregation of tree populations provides a long-term perspective. While
      spatial distributions have provided only weak evidence for NDD so far, the
      opposing effects of environmental heterogeneity might have confounded previous
      analyses. Here we use a novel statistical technique to control for environmental
      heterogeneity while testing whether spatial aggregation decreases with tree size
      in four tropical forests. We provide evidence for NDD in 22% of the 139 tree
      species analyzed and show that environmental heterogeneity can obscure the
      spatial signal of NDD. Environmental heterogeneity contributed to aggregation in
      84% of species. We conclude that both biotic interactions and environmental
      heterogeneity play crucial roles in shaping tree dynamics in tropical forests.

PMID- 21939069
TI  - On the generality of a climate-mediated shift in the distribution of the American
      pika (Ochotona princeps).
AB  - Alpine species are among those most threatened by climatic shifts due to their
      physiological and geographic constraints. The American pika (Ochotona princeps),
      a small mammal found in mountainous, rocky habitats throughout much of western
      North America, has experienced recent population extirpations in the Great Basin
      linked to climatic drivers. It remains unclear whether these patterns of climate
      related loss extend to other portions of the species' range. We investigated the
      distribution of the American pika and the climatic processes shaping this
      distribution within the Southern Rocky Mountain region. Results from a survey of
      69 sites historically occupied by pikas indicate that only four populations have
      been extirpated within this region over the past few decades. Despite relatively
      few extirpations, low annual precipitation is implicated as a limiting factor for
      pika persistence in the Southern Rockies. Extirpations occurred only at sites
      that were consistently dry over the last century. While there was no climate
      change signal in our results, these data provide valuable insight into the
      potential future effects of climate change on O. princeps throughout its range.

PMID- 21939070
TI  - The transition from isolated patches to a metapopulation in the eastern collared
      lizard in response to prescribed fires.
AB  - Habitat fragmentation often arises from human-induced alterations to the matrix
      that reduce or eliminate dispersal between habitat patches. Elimination of
      dispersal increases local extinction and decreases recolonization. These
      phenomena were observed in the eastern collared lizard (Crotaphytus collaris
      collaris), which lives in the mid-continental highland region of the Ozarks
      (Missouri, USA) on glades: habitats of exposed bedrock that form desert-like
      habitats imbedded in a woodland matrix. With the onset of woodland fire
      suppression, glade habitats degenerated and the woodland matrix was altered to
      create a strong barrier to dispersal. By 1980, lizard populations in the Ozarks
      were rapidly going extinct. In response to this decline, some glades were
      restored by clearing and burning. Starting in 1984, collared lizard populations
      were translocated onto these restored habitats. The translocated populations
      persisted but did not colonize nearby glades or disperse among one another. In
      1994 prescribed woodland fires were initiated, which unleashed much dispersal and
      colonizing behavior. Dispersal was highly nonrandom by both intrinsic variables
      (age, gender) and extrinsic variables (overall demography, glade population
      sizes, glade areas, landscape features), resulting in different classes of
      lizards being dominant in creating demographic cohesiveness among glades,
      colonizing new glades on a mountain, and colonizing new mountain systems. A
      dramatic transition was documented from isolated fragments, to a nonequilibrium
      colonizing metapopulation, and finally to a stable metapopulation. This
      transition is characterized by the convergence of rates of extinction and
      recolonization and a major alteration of dispersal probabilities and pattern in
      going from the nonequilibrium to stable metapopulation states.

PMID- 21939071
TI  - Biotic resistance via granivory: establishment by invasive, naturalized, and
      native asters reflects generalist preference.
AB  - Escape from specialist natural enemies is frequently invoked to explain exotic
      plant invasions, but little attention has been paid to how generalist consumers
      in the recipient range may influence invasion. We examined how seed preferences
      of the widespread generalist granivore Peromyscus maniculatus related to
      recruitment of the strongly invasive exotic Centaurea stoebe and several weakly
      invasive exotics and natives by conducting laboratory feeding trials and seed
      addition experiments in the field. Laboratory feeding trials showed that P.
      maniculatus avoided consuming seeds of C. stoebe relative to the 12 other species
      tested, even when seeds of alternative species were 53-94% smaller than those of
      C. stoebe. Seed addition experiments conducted in and out of rodent exclosures
      revealed that weakly invasive exotics experienced relatively greater release from
      seed predation than C. stoebe, although this was not the case for natives. Seed
      mass explained 81% of the variation in recruitment associated with rodent
      exclusion for natives and weak invaders, with larger-seeded species benefiting
      most from protection from granivores. However, recruitment of C. stoebe was
      unaffected by rodent exclusion, even though the regression model predicted seeds
      of correspondingly large mass should experience substantial predation. These
      combined laboratory and field results suggest that generalist granivores can be
      an important biological filter in plant communities and that species-specific
      seed attributes that determine seed predation may help to explain variation in
      native plant recruitment and the success of exotic species invasions.

PMID- 21939072
TI  - Invasional meltdown: invader-invader mutualism facilitates a secondary invasion.
AB  - In multiply invaded ecosystems, introduced species should interact with each
      other as well as with native species. Invader-invader interactions may affect the
      success of further invaders by altering attributes of recipient communities and
      propagule pressure. The invasional meltdown hypothesis (IMH) posits that positive
      interactions among invaders initiate positive population-level feedback that
      intensifies impacts and promotes secondary invasions. IMH remains controversial:
      few studies show feedback between invaders that amplifies their effects, and none
      yet demonstrate facilitation of entry and spread of secondary invaders. Our
      results show that supercolonies of an alien ant, promoted by mutualism with
      introduced honeydew-secreting scale insects, permitted invasion by an exotic land
      snail on Christmas Island, Indian Ocean. Modeling of land snail spread over 750
      sites across 135 km2 over seven years showed that the probability of land snail
      invasion was facilitated 253-fold in ant supercolonies but impeded in intact
      forest where predaceous native land crabs remained abundant. Land snail
      occurrence at neighboring sites, a measure of propagule pressure, also promoted
      land snail spread. Site comparisons and experiments revealed that ant
      supercolonies, by killing land crabs but not land snails, disrupted biotic
      resistance and provided enemy-free space. Predation pressure on land snails was
      lower (28.6%), survival 115 times longer, and abundance 20-fold greater in
      supercolonies than in intact forest. Whole-ecosystem suppression of supercolonies
      reversed the probability of land snail invasion by allowing recolonization of
      land crabs; land snails were much less likely (0.79%) to invade sites where
      supercolonies were suppressed than where they remained intact. Our results
      provide strong empirical evidence for IMH by demonstrating that mutualism between
      invaders reconfigures key interactions in the recipient community. This
      facilitates entry of secondary invaders and elevates propagule pressure,
      propagating their spread at the whole-ecosystem level. We show that
      identification and management of key facilitative interactions in invaded
      ecosystems can be used to reverse impacts and restore resistance to further
      invasions.

PMID- 21939073
TI  - Herbivory-mediated pollinator limitation: negative impacts of induced volatiles
      on plant-pollinator interactions.
AB  - Although induced plant responses to herbivory are well studied as mechanisms of
      resistance, how induction shapes community interactions and ultimately plant
      fitness is still relatively unknown. Using a wild tomato, Solanum peruvianum,
      native to the Peruvian Andes, we evaluated the disruption of pollination as a
      potential ecological cost of induced responses. More specifically, we tested the
      hypothesis that metabolic changes in herbivore-attacked plants, such as the
      herbivore-induced emission of volatile organic compounds (VOCs), alter pollinator
      behavior and consequentially affect plant fitness. We conducted a series of
      manipulative field experiments to evaluate the role of herbivore-induced
      vegetative and floral VOC emissions as mechanisms by which herbivory affects
      pollinator behavior. In field surveys and bioassays in the plants' native
      habitat, we found that real and simulated herbivory (methyl jasmonate
      application) reduced attractiveness of S. peruvianum flowers to their native
      pollinators. We show that reduced pollinator preference, not resource limitation
      due to leaf tissue removal, resulted in reduced seed set. Solitary bee
      pollinators use floral plant volatiles, emitted in response to herbivory or
      methyl jasmonate treatment, as cues to avoid inflorescences on damaged plants.
      This herbivory-induced pollinator limitation can be viewed as a general cost of
      induced plant responses as well as a specific cost of herbivory-induced volatile
      emission.

PMID- 21939074
TI  - Dynamic selective environments and evolutionary traps in human-dominated
      landscapes.
AB  - Human activities can alter selective environments in ways that can reduce the
      usefulness of certain ornamental traits as honest signals of individual quality
      and, in some cases, may create evolutionary traps, where rapid changes in
      selective environments result in maladaptive behavioral decisions. Using the
      sexually dichromatic, socially monogamous Northern Cardinal (Cardinalis
      cardinalis) as a model, we hypothesized that urbanization would erode the
      relationship between plumage coloration and reproductive success. Because the
      exotic Amur honeysuckle (Lonicera maackii) provides carotenoids, is a preferred
      habitat attribute, and increases vulnerability to nest predation, we predicted
      the presence of an evolutionary trap, whereby the brightest males would achieve
      the lowest reproductive success. Working at 14 forests in Ohio, USA, 2006-2008,
      we measured plumage color, monitored reproduction, and quantified habitat within
      territories. In rural landscapes, the brightest males bred earliest in the season
      and secured more preferred territories; however, annual reproduction declined
      with plumage brightness. Coloration of urban males was not associated with
      territory attributes or reproduction. Female redness across all landscapes was
      negatively related to reproduction. Poor reproductive performance of otherwise
      higher-quality males probably resulted from preferences for honeysuckle, which
      reduces annual reproduction when used as a nesting substrate early in the season.
      In this way, exotic shrubs prompted an evolutionary trap that was avoided in
      urban forests where anthropogenic resources disassociated male color and
      reproductive phenology and success. Our study illustrates how modified selective
      environments in human-dominated landscapes might shape microevolutionary
      processes in wild bird populations.

PMID- 21939075
TI  - Range-wide effects of breeding- and nonbreeding-season climate on the abundance
      of a Neotropical migrant songbird.
AB  - Geographic variation in the population dynamics of a species can result from
      regional variability in climate and how it affects reproduction and survival.
      Identifying such effects for migratory birds requires the integration of
      population models with knowledge of migratory connectivity between breeding and
      nonbreeding areas. We used Bayesian hierarchical models with 26 years of Breeding
      Bird Survey data (1982-2007) to investigate the impacts of breeding- and
      nonbreeding-season climate on abundance of American Redstarts (Setophaga
      ruticilla) across the species range. We focused on 15 populations defined by Bird
      Conservation Regions, and we included variation across routes and observers as
      well as temporal trends and climate effects. American Redstart populations that
      breed in eastern North America showed increased abundance following winters with
      higher plant productivity in the Caribbean where they are expected to overwinter.
      In contrast, western breeding populations showed little response to conditions in
      their expected wintering areas in west Mexico, perhaps reflecting lower migratory
      connectivity or differential effects of winter rainfall on individuals across the
      species range. Unlike the case with winter climate, we found few effects of
      temperature prior to arrival in spring (March-April) or during the nesting period
      (May-June) on abundance the following year. Eight populations showed significant
      changes in abundance, with the steepest declines in the Atlantic Northern Forest
      (-3.4%/yr) and the greatest increases in the Prairie Hardwood Transition (4%/yr).
      This study emphasizes how the effects of climate on populations of migratory
      birds are context dependent and can vary depending on geographic location and the
      period of the annual cycle. Such knowledge is essential for predicting regional
      variation in how populations of a species might vary in their response to climate
      change.

PMID- 21939076
TI  - The effects of variable predation risk on foraging and growth: less risk is not
      necessarily better.
AB  - There is strong evidence that the way prey respond to predation risk can be
      fundamentally important to the structuring and functioning of natural ecosystems.
      The majority of work on such nonconsumptive predator effects (NCEs) has examined
      prey responses under constant risk or constant safety. Hence, the importance of
      temporal variation in predation risk, which is ubiquitous in natural systems, has
      received limited empirical attention. In addition, tests of theory (e.g., the
      risk allocation hypothesis) on how prey allocate risk have relied almost
      exclusively on the behavioral responses of prey to variation in risk. In this
      study, we examined how temporal variation in predation risk affected NCEs on prey
      foraging and growth. We found that high risk, when predictable, was just as
      energetically favorable to prey as safe environments that are occasionally pulsed
      by risk. This pattern emerged because even episodic pulses of risk in otherwise
      safe environments led to strong NCEs on both foraging and growth. However, NCEs
      more strongly affected growth than foraging, and we suggest that such effects on
      growth are most important to how prey ultimately allocate risk. Hence, exclusive
      focus on behavioral responses to risk will likely provide an incomplete
      understanding of how NCEs shape individual fitness and the dynamics of ecological
      communities.

PMID- 21939077
TI  - Plant genotype and nitrogen loading influence seagrass productivity,
      biochemistry, and plant-herbivore interactions.
AB  - Genetic variation within and among key species can have significant ecological
      consequences at the population, community, and ecosystem levels. In order to
      understand ecological properties of systems based on habitat-forming clonal
      plants, it is crucial to clarify which traits vary among plant genotypes and how
      they influence ecological processes, and to assess their relative contribution to
      ecosystem functioning in comparison to other factors. Here we used a mesocosm
      experiment to examine the relative influence of genotypic identity and extreme
      levels of nitrogen loading on traits that affect ecological processes (at the
      population, community, and ecosystem levels) for Zostera marina, a widespread
      marine angiosperm that forms monospecific meadows throughout coastal areas in the
      Northern Hemisphere. We found effects of both genotype and nitrogen addition on
      many plant characteristics (e.g., aboveground and belowground biomass), and these
      were generally strong and similar in magnitude, whereas interactive effects were
      rare. Genotypes also strongly differed in susceptibility to herbivorous isopods,
      with isopod preference among genotypes generally matching their performance in
      terms of growth and survival. Chemical rather than structural differences among
      genotypes drove these differences in seagrass palatability. Nitrogen addition
      uniformly decreased plant palatability but did not greatly alter the relative
      preferences of herbivores among genotypes, indicating that genotype effects are
      strong. Our results highlight that differences in key traits among genotypes of
      habitat-forming species can have important consequences for the communities and
      ecosystems that depend on them and that such effects are not overwhelmed by known
      environmental stressors.

PMID- 21939078
TI  - The role of canopy structural complexity in wood net primary production of a
      maturing northern deciduous forest.
AB  - The even-aged northern hardwood forests of the Upper Great Lakes Region are
      undergoing an ecological transition during which structural and biotic complexity
      is increasing. Early-successional aspen (Populus spp.) and birch (Betula
      papyrifera) are senescing at an accelerating rate and are being replaced by
      middle-successional species including northern red oak (Quercus rubra), red maple
      (Acer rubrum), and white pine (Pinus strobus). Canopy structural complexity may
      increase due to forest age, canopy disturbances, and changing species diversity.
      More structurally complex canopies may enhance carbon (C) sequestration in old
      forests. We hypothesize that these biotic and structural alterations will result
      in increased structural complexity of the maturing canopy with implications for
      forest C uptake. At the University of Michigan Biological Station (UMBS), we
      combined a decade of observations of net primary productivity (NPP), leaf area
      index (LAI), site index, canopy tree-species diversity, and stand age with canopy
      structure measurements made with portable canopy lidar (PCL) in 30 forested
      plots. We then evaluated the relative impact of stand characteristics on
      productivity through succession using data collected over a nine-year period. We
      found that effects of canopy structural complexity on wood NPP (NPPw) were
      similar in magnitude to the effects of total leaf area and site quality.
      Furthermore, our results suggest that the effect of stand age on NPPw is mediated
      primarily through its effect on canopy structural complexity. Stand-level
      diversity of canopy-tree species was not significantly related to either canopy
      structure or NPPw. We conclude that increasing canopy structural complexity
      provides a mechanism for the potential maintenance of productivity in aging
      forests.

PMID- 21939079
TI  - Seedling growth responses to soil resources in the understory of a wet tropical
      forest.
AB  - Plant growth responses to resources may be an important mechanism that influences
      species' distributions, coexistence, and community structure. Irradiance is
      considered the most important resource for seedling growth in the understory of
      wet tropical forests, but multiple soil nutrients and species have yet to be
      examined simultaneously with irradiance under field conditions. To identify
      potentially limiting resources, we modeled tree seedling growth as a function of
      irradiance and soil nutrients across five sites, spanning a soil fertility
      gradient in old-growth, wet tropical forests at La Selva Biological Station,
      Costa Rica. We measured an array of soil nutrients including total nitrogen
      (total N), inorganic N (nitrate [NO3-] and ammonium [NH4+]), phosphate (PO4-),
      and sum of base cations (SBC; potassium, magnesium, and calcium). Shade in the
      forest understory did not preclude seedling growth correlations with soil
      nutrients. Irradiance was a significant predictor of growth in 52% of the
      species, inorganic N in 54% (NO3- in 32%; NH4+ in 34%), total N in 47%, SBC in
      39%, and PO4- in 29%. Overall, growth was correlated with both irradiance and
      soil nutrients in 45% of species and with soil nutrients only in an additional
      48%; rarely was irradiance alone correlated with growth. Contrary to
      expectations, the magnitudes of growth effects, assessed as the maximum growth
      response to significant resources for each species, were similar for irradiance
      and most soil nutrients. Among species whose growth correlated with soil
      nutrients, the rank importance of nutrient effects was SBC, followed by N (total
      N, NO3-, and/or NH4+) and PO4-. Species' growth responsiveness (i.e., magnitudes
      of effect) to irradiance and soil nutrients was negatively correlated with
      species' shade tolerance (survival under 1% full sun). In this broad survey of
      species and resources, the nearly ubiquitous effects of soil nutrients on
      seedling growth challenge the idea that soil nutrients are less important than
      irradiance in the light-limited understory of wet tropical forests.

PMID- 21939080
TI  - Global distribution of a key trophic guild contrasts with common latitudinal
      diversity patterns.
AB  - Most hypotheses explaining the general gradient of higher diversity toward the
      equator are implicit or explicit about greater species packing in the tropics.
      However, global patterns of diversity within guilds, including trophic guilds
      (i.e., groups of organisms that use similar food resources), are poorly known. We
      explored global diversity patterns of a key trophic guild in stream ecosystems,
      the detritivore shredders. This was motivated by the fundamental ecological role
      of shredders as decomposers of leaf litter and by some records pointing to low
      shredder diversity and abundance in the tropics, which contrasts with diversity
      patterns of most major taxa for which broad-scale latitudinal patterns haven been
      examined. Given this evidence, we hypothesized that shredders are more abundant
      and diverse in temperate than in tropical streams, and that this pattern is
      related to the higher temperatures and lower availability of high-quality leaf
      litter in the tropics. Our comprehensive global survey (129 stream sites from 14
      regions on six continents) corroborated the expected latitudinal pattern and
      showed that shredder distribution (abundance, diversity and assemblage
      composition) was explained by a combination of factors, including water
      temperature (some taxa were restricted to cool waters) and biogeography (some
      taxa were more diverse in particular biogeographic realms). In contrast to our
      hypothesis, shredder diversity was unrelated to leaf toughness, but it was
      inversely related to litter diversity. Our findings markedly contrast with global
      trends of diversity for most taxa, and with the general rule of higher consumer
      diversity at higher levels of resource diversity. Moreover, they highlight the
      emerging role of temperature in understanding global patterns of diversity, which
      is of great relevance in the face of projected global warming.

PMID- 21939081
TI  - The probabilistic niche model reveals substantial variation in the niche
      structure of empirical food webs.
AB  - The structure of food webs, complex networks of interspecies feeding
      interactions, plays a crucial role in ecosystem resilience and function, and
      understanding food web structure remains a central problem in ecology. Previous
      studies have shown that key features of empirical food webs can be reproduced by
      low-dimensional "niche" models. Here we examine the form and variability of food
      web niche structure by fitting a probabilistic niche model to 37 empirical food
      webs, a much larger number of food webs than used in previous studies. The model
      relaxes previous assumptions about parameter distributions and hierarchy and
      returns parameter estimates for each species in each web. The model significantly
      outperforms previous niche model variants and also performs well for several webs
      where a body-size-based niche model performs poorly, implying that traits other
      than body size are important in structuring these webs' niche space. Parameter
      estimates frequently violate previous models' assumptions: in 19 of 37 webs,
      parameter values are not significantly hierarchical, 32 of 37 webs have
      nonuniform niche value distributions, and 15 of 37 webs lack a correlation
      between niche width and niche position. Extending the model to a two-dimensional
      niche space yields networks with a mixture of one- and two-dimensional niches and
      provides a significantly better fit for webs with a large number of species and
      links. These results confirm that food webs are strongly niche-structured but
      reveal substantial variation in the form of the niche structuring, a result with
      fundamental implications for ecosystem resilience and function.

PMID- 21939082
TI  - Climate-induced reaction norms for life-history traits in pythons.
AB  - Climate change modelers predict increasingly frequent "extreme events," so it is
      critical to quantify whether organismal responses (such as reproductive output)
      measured over the range of usual climatic conditions can predict responses under
      more extreme conditions. In a 20-year field study on water pythons (Liasis
      fuscus), we quantified the effects of climatically driven annual variation in
      food supply on demographic traits of female pythons (feeding rate, body size,
      body mass, and reproductive output). Reaction norms linking food supply to
      feeding rates and residual body mass were broadly linear, whereas norms linking
      food supply to female body size became curvilinear when a dramatic (flooding
      induced) famine reduced the mean body size at sexual maturity. Thus, the reaction
      norms recorded over 16 years of mal" (albeit highly variable) climatic conditions
      gave little insight into the population's response to a more extreme nutritional
      crisis.

PMID- 21939083
TI  - [The new dietary reference intakes from the Institute of Medicine for calcium and
      vitamin D].

PMID- 21939084
TI  - [Lucie Tremblay. Humanism--respect for dignity--energy].

PMID- 21939085
TI  - [The story behind autism and the MMR vaccine: a medical scandal in the news].

PMID- 21939086
TI  - [Reducing sodium in the Canadian diet: a challenge for the cheese industry].

PMID- 21939087
TI  - [Where are we? Does current nurse training allow nurses to adequately evaluate
      physical and mental health?].

PMID- 21939088
TI  - [Stomas. Part I. Causes and types of interventions. Principles of surgical
      stomas].

PMID- 21939089
TI  - [The bathing of patients with alzheimer's. A daily challenge].

PMID- 21939091
TI  - [Food allergies. The boxed lunch. The exposure to food allergies at school].

PMID- 21939090
TI  - [The death of Mohamed. Jimma, Ethiopia. Chronicles of a nurse in the heart of a
      rural village].

PMID- 21939092
TI  - [Food allergies. Preventive properties of breast milk].

PMID- 21939093
TI  - [Returning to school increases the opportunity for lice].

PMID- 21939094
TI  - [Asthma and chlorine. Do indoor chlorinated pools lead to childhood asthma?].

PMID- 21939095
TI  - [Testimony of a school nurse. In this interview, Thesy Louis shares her
      experience].

PMID- 21939096
TI  - [Oops! What to do if you forget to take your 24/4 contraceptive pill].

PMID- 21939097
TI  - [Atypical antipsychotics given to the elderly suffering from dementia and living
      at home: an important clinical follow-up. Knowing the secondary effects].

PMID- 21939098
TI  - [Medication errors].

PMID- 21939099
TI  - [Anti-inflammatory non-steroidal + proton pump inhibitor = a winning
      combination!].

PMID- 21939100
TI  - [Planning for retirement. Beyond figures].

PMID- 21939101
TI  - New approach for handling glass ionomers in restorative dentistry.
AB  - Potentially toxic products like the existing composites and their derivatives may
      harm both patients and dentists and therefore prudence is recommended,
      particularly in dentistry for children. Biocompatible glassionomers are a
      meaningful alternative for composites but have low strength and wear resistance.
      Mechanical properties of self curing GIC's can be improved by using heat-curing
      technique making them command set materials. This article is showing the clinical
      possibilities using this technique. The forming of the so-called pseudo enamel
      (Fluor-Apatite) is a unique property. Using this new methods lead to long lasting
      and biocompatible posterior GIC restorations which can mechanically in strength
      and wear but also in esthetics compete with posterior composites.

PMID- 21939102
TI  - [Are you afraid of open bite?].
AB  - Treatment of open bite malocclusion is a challenge for both the orthodontist and
      the patient. The key to successful treatment are careful evaluation, that leads
      to correct diagnosis and treatment plan, as well as meticulous cooperation on
      behalf of the patient. There are many treatment options starting with follow up
      and orofacial myofunctional therapy, and concluding with orthosurgical
      correction. The tendency to relapse and reopening the bite must be emphasized to
      the patient before initiation of the orthodontic treatment. It is highly
      recommended in indicated cases to include orofacial myofunctional therapy in
      combination with the orthodontic treatment. New modalities of treatment give
      great promise for the future, and enable us to intrude posterior teeth using
      skeletal anchorage. However, it is still unknown whether these new treatment
      modalities will give better stability for open bite correction.

PMID- 21939103
TI  - [Reconstruction of the alveolar ridge by osteodistraction for implant placement].
AB  - Alveolar Distraction is a method for reconstructing a deficient or atrophic
      alveolar bone. Alveolar ridge reconstruction may be indicated for the atrophic
      alveolar process resulting from maxillofacial trauma, periodontal disease, or
      post aggressive large cyst or tumor resection. The aim of this paper is to
      demonstrate the method of reconstruction of the alveolar ridge by Distraction
      Osteogenesis. A total of 32 patients were treated. An alveolar segmental
      osteotomy was carried out and the distraction device was mounted. In patients
      with an extensive alveolar defect two distraction devices were placed in order to
      better control the vector of elongation in both bone edges. The distraction was
      started on the fourth post-operative day at a rate of 0.5 mm/day as necessary and
      according to the length of the distraction device, followed by a consolidation
      period of 90 days. Subsequently, the devices were removed, and dental implants
      were placed for osteointegration. The amount of elevation was 8-15mm. All the
      patients had panoramic x ray before the distraction, during the lengthening, at
      the end of distraction and after removal of the device. Early mineralization in
      the distracted area was seen radiographically during the consolidation period
      that increased after device removal. As a result of alveolar distraction, a
      segment of mature bone was transported vertically in order to lengthen the crest
      for better implant anchorage, either for esthetic purposes or for functional
      prosthetic requirements. A total of 68 implants were introduced. In follow-up at
      24 months, failure of only one implant was noted, due to inadequate transported
      bone stability. In conclusion, distraction osteogenesis is an alternative
      treatment in moderate to severe alveolar deficiencies for an ideal three
      dimensional reconstruction with no need for bone harvesting. This method offers
      the possibility to place dental implants in a correct position to obtain proper
      prosthetic results.

PMID- 21939104
TI  - [Orthodontic treatment in periodontal patients].
AB  - Orthodontic treatment poses a significant challenge in patients suffering from
      periodontal disease. Providing orthodontic treatment to periodontal patients
      should be carefully planned and performed in a tight collaboration between the
      orthodontist and periodontist. Resolution and stabilization of the periodontal
      condition is a pre-requisite for orthodontic treatment initiation. Careful oral
      hygiene performance and highly frequent recall periodontal visits are also
      crucial. Pre- or post- orthodontic periodontal surgery might help providing
      better treatment outcomes.

PMID- 21939107
TI  - [Clinical photography].

PMID- 21939108
TI  - Occupational hazards in dentistry.
AB  - Professional risk factors in dentistry may harm the dentist and the dental team.
      It is essential for the dentist to recognize these risk factors and protect
      against them. Among the various organs that are vulnerable in the dental
      situation are (in a nut-shell): The eyes, the ears, the respiratory system, the
      palm of the hand, and the back and the vertebrae. In addition, the dentist and
      the dental team must recognizes the potential for Hepatitis (A, B, C, D, E), and
      for the acquired immune deficiency syndrome due to the HIV virus. The primary
      means for protecting against these potential hazardous factors is meticulously
      keeping proper working conditions such as good ventilation of the operating room,
      using face masks which are capable of blocking even small particles, using eye
      protection and gloves, and proper seating at the chair. It is reasonable to adopt
      a routine of taking a vaccine against Influenza and Hepatitis B, and to routinely
      check the level of antibodies for Hepatitis B. Personal accidents- and severe
      diseases-insurances, as well as insurance against losing the ability to work are
      advised for every dentist.

PMID- 21939106
TI  - [Orthodontic tooth movement under extracorporeal shock wave therapy: the
      characteristics of the inflammatory reaction--a preliminary study].
AB  - Extracorporeal generated shock waves were introduced in medical therapy
      approximately 20 years ago in order to disintegrate kidney stones. Over the last
      10 years, extracorporeal generated shock waves have been used to stimulate
      healing processes. No report to date has examined its influence on different
      inflammation mediators and growth factors in the periodontium. Orthodontic tooth
      movement is a model including the induction of an aseptic inflammation and its
      resolution. We conducted a preliminary study to investigate the periodontium
      cytokine concentration fluctuations after induction of orthodontic force with and
      without extracorporeal shock wave therapy (ESWT) in a rat model. An orthodontic
      appliance was fabricated and applied between the molars and the incisors of rats.
      The rats were treated by a single episode of 1000 shock waves and gingival
      crevicular fluid was collected for 3 days. The concentration of typical acute
      phase cytokines was evaluated by ELISA assay. Of the three tested cytokines, IL
      1beta was the only detected cytokine along the study timeframe. IL-1beta
      concentration rose in both the treated and non treated shockwave groups on the
      first day, however it was statistically significantly higher in the treated group
      on day 2. On day 3, IL-1beta concentrations in both groups decreased and reached
      a lower level in the treated group, revealing a statistically significant
      difference than its level on the previous day. The application of ESWT during
      orthodontic force induction enhances IL-1beta production as part of mechanical
      forces transduction triggering a biologic response, which may contribute to
      accelerated periodontal remodeling and therefore foreshortening the orthodontic
      tooth movement period.

PMID- 21939109
TI  - [The future of medicine in Israel].

PMID- 21939110
TI  - [Workload, burnout and need to recover among female residents in internal
      medicine and family medicine].
AB  - BACKGROUND: The Israeli medical residents' workload in hospitals is enormous,
      especially in the internaL wards, due to a severe lack of manpower and the demand
      to carry out many shifts. The workload of residents who practice in the community
      is rising as well: family physicians are required to achieve quality objectives
      in treating chronic diseases while the time dedicated to each patient is
      shortening. Creating a family usually parallels to this phase, causing home-work
      conflict among the residents. Consequently, the residents are Liable to develop
      burnout during their internship. AIMS: Quantification and characterization of the
      need to recover from workload among internal ward resident mothers with young
      children, compared to family medicine resident mothers with young children, and
      to investigate the relation between workload and the development of burnout in
      those groups. METHODS: A cross-sectional study was conducted comparing 30 female
      internal ward residents with young children to 38 female family medicine
      residents with young children, by using workload, burnout, sleep quality and need
      to recover questions. RESULTS: Although the workload reported by female internal
      ward residents was higher than that reported by family medicine residents [p <
      0.01, t = 2.73), no differences were found in the need for recovery and the
      extent of the burnout. Positive correlations were found between the workload and
      the burnout (p < 0.05, r = 0.30), the workload and the need for recovery (p <
      0.001, r = 0.58) and between the burnout and the need for recovery (p < 0.001, r
      = 0.67]. DISCUSSION: It seems that both groups are equally burned-out and need to
      recover after work. Our article calls for improvement of working conditions in
      both residencies.

PMID- 21939111
TI  - [President Obama's health care reform: lessons to and from the Israeli health
      care system].
AB  - In March 2010 the United States enacted the most significant health care reform
      in several decades. The Patient Protection and Affordable Care Act, amongst other
      provisions, addresses two of the main current shortcomings of the U.S. health
      system: the large portion of the population that are uninsured and the high
      percentage of hsealth expenditures (mostly private] which amounts to about 16% of
      the GDP. Changes to the current structure and financing of the U.S. health system
      will have implications for other health systems, for science (e.g., through
      enhanced federal funding for comparative effectiveness research), and for
      technological advance (e.g., through accelerated development and use of
      electronic health records). There are several lessons from the reform, and the
      factors leading to its implementation, for the Israeli health system. Firstly,
      the basic principles of the Israeli health system are a source of pride, and
      undermining its main values can have deleterious effects. Overreliance on
      private, out-of-pocket, spending and lack of support for public practice of
      medicine (in community and hospital settings) will weaken the public sector,
      strengthen the private sector, and could result in a tiered lower quality and
      less accessible public system with greater widening of gaps in health and health
      care utilization. This paper reviews the main provisions of the U.S. health care
      reform and the potential implications for the IsraeLi health system.

PMID- 21939112
TI  - [Which complementary and alternative medicine modalities are integrated within
      Israeli healthcare organizations and do they match the public's preferences?].
AB  - INTRODUCTION: Complementary and alternative medicine (CAM) is a broad term that
      encompasses diverse healthcare modalities that emanate from a variety of healing
      cultures. One of the basic principles of CAM is the promotion of cultural
      pluralism and openness to diverse cultural aspects of health and illness. Some
      CAM modalities have been integrated into Israeli healthcare organizations over
      the past two decades. AIM: The objective of this research was to examine whether
      the integrated CAM modalities match the preferences of Israel's diverse ethnic
      groups. METHODOLOGY: The research was conducted in northern Israel, an area
      marked by ethnic and religious diversity. We gathered information about the types
      of CAM modalities included in the clinics of all four public health funds health
      maintenance organizations (HMOs)--by means of a telephone survey. This data was
      assessed in relation to previous data regarding patients' preferences on
      integrating CAM in community care. RESULTS: The 4 HMOs offer 24 CAM modalities
      within 58 clinics in northern Israel. The most common CAM modalities are:
      reflexology, Chinese Medicine and acupuncture, massage, shiatsu, twina,
      homeopathy and naturopathy. These modalities partly match the Jewish and Arab
      populations' preferences concerning Chinese medicine and touch/movement
      modalities. The Arab population, however, which reports greater use of folk
      traditional medicine, such as consultation with healers and use of herbal
      medicine, do not have these treatment options available within healthcare
      organizations. CONCLUSIONS: Western-oriented CAM modalities are integrated within
      the IsraeLi HMOs, while local folk-traditional medicine is not. The integrated
      modalities accord with the Jewish populations' preferences more than with those
      of the Arab population. DISCUSSION: Some of the factors that influence
      integration are discussed. Certain homegrown traditional healthcare modalities,
      such as use of local medicinal herbs, should be considered for addition to
      current CAM practices. Developing integrative medicine within a common Jewish
      Arabic space could have medical as well as social-cultural advantages.

PMID- 21939113
TI  - [Blood letting by cupping--a "medical" vignette].
AB  - This is a report on a "clinic" in northern Israel, in which a considerable number
      of people are treated by bloodletting. The authors witnessed the procedures of
      cupping various areas of the body and puncturing them by needles. The person in
      charge, who does not have any medical education or Licensing, and a client were
      interviewed. This report aims to bring to the attention of the medical community
      a procedure that spreads within the framework of so-called alternative medicine.

PMID- 21939114
TI  - [Integrating complementary medicine in oncology supportive care: assessment of
      patients' needs and expectations during chemotherapy].
AB  - BACKGROUND: During the Last decade complementary medicine is gradually being
      integrated within conventional oncology care in Western countries. In 2008, an
      integrative oncology program was implemented within the Clalit Oncology Service
      (COS) of the Haifa and Western-Galilee district of Clalit Health Organization
      aiming to promote patients' well-being during chemotherapy and in advanced
      disease. OBJECTIVE: To identify needs and distress of patients with regard to
      combining complementary medicine with the supporting treatment for improvement of
      quality of life. METHODS: A study using semi-constructed interviews with 31
      patients during chemotherapy was performed at two outpatient oncology centers of
      the Clalit HMO in northern Israel. RESULTS: Most participants reported
      significant deterioration in their quality of life during chemotherapy, mainly
      related to fatigue, work cessation and mood disorder. Interest in complementary
      medicine significantly correlated with the participants' awareness of the mind
      body connection. Most participants reported on their interest to consult with
      physicians specializing in complementary medicine as an integral part of the
      oncology service care. The most favorable complementary therapies reported by
      patients were nutritional counseling, herbal medicine and traditional healing.
      CONCLUSIONS: Asking patients during chemotherapy on their beliefs regarding mind
      and body connections may be used as a screening question to identify patients
      interested in experiencing complementary therapies. Integrating physician
      counseling regarding complementary medicine within the oncology service may
      address patients' needs and concerns by matching therapies to specific symptoms
      and chemotherapy side-effects.

PMID- 21939115
TI  - [The influence of single immersion in Dead Sea water on glucose, insulin,
      cortisol and C-peptide levels in type 2 diabetes mellitus patients].
AB  - BACKGROUND: Bathing in sweet or mineral water can induce significant
      physiological changes in several body systems including the endocrine system. To
      date, there have only been a small number of reports that balneology can reduce
      blood sugar Levels in patients with type 2 diabetes mellitus (DM]. OBJECTIVE: To
      compare the effects of a single immersion in sweet or mineral water on blood
      glucose, insulin, cortisol and c-peptide levels in patients with type 2 DM.
      METHODS: Fourteen patients with type 2 DM and six healthy volunteers were
      immersed in water twice, with an interval of two weeks in between immersions. The
      first immersion was in Dead Sea water and the second in sweet water. In both
      cases the water was warmed to a temperature of 35 degrees C and the bath
      continued for 20 minutes. Three blood samples were taken from each of the
      participants at every immersion. The first sample was taken just prior to the
      start of immersion, the second sample was taken directly at the end of immersion,
      and the third sample, one hour later. In each sample the blood was tested for
      glucose, insulin, cortisol, and c-peptide Levels. RESULTS: A significant
      reduction was seen in blood glucose levels among DM patients who were immersed in
      Dead Sea water. The glucose levels dropped from a base Line level of 163 +/- 32.4
      mg/dl prior to immersion, to 151 +/- 28.8 at the end of the immersion, and to 141
      +/- 34.6 an hour later. All the differences were statistically significant:
      baseline to end of immersion (P = 0.006), end of immersion to one hour later (P =
      0.024), and baseline to one hour after immersion (P=0.005). The difference in
      blood glucose was much Less following immersion in sweet water and did not reach
      statistical significance except between the end of immersion and one hour later.
      No significant differences were found for insulin, cortisol, and c-peptide levels
      between DM patients and healthy volunteers following immersion. CONCLUSION: One
      time immersion in Dead Sea water reduces blood glucose levels in type 2 DM
      patients compared to healthy volunteers.

PMID- 21939116
TI  - [What determines the market shares of the health funds in Israeli localities?].
AB  - BACKGROUND: Four health funds operate nationally in Israel, but their local
      market shares vary dramatically across localities. OBJECTIVES: To identify the
      main localities' characteristics which affect the size of the market shares of
      the various health funds. METHODS: A total of 60 Localities with more than 20,000
      inhabitants were chosen. The following Localities' characteristics were retrieved
      for the year 2004: the market shares of the four health funds, average income,
      standardized mortality ratio (SMR), periphery index, the age structure, the
      distance from the nearest general hospital, the share of Arab population, and
      size. Four market share equations were estimated using SURE (seemingly unrelated
      regressions estimation), allowing for inter-equation correlations. RESULTS: The
      results show that the market shares of the different health funds are affected by
      different factors. Clalit Health Services' (CHS) share increases with the
      distance from Tel Aviv and SMR, and decreases with the level of mean income and
      the distance from the nearest CHS hospital. Leumit's market share increases only
      with the distance from a CHS's hospital. The market share of Maccabi Healthcare
      Services is higher in central localities, Jewish localities, small cities and
      further away from a non-CHS hospital. Meuhedet's market share is higher in big
      cities, rich and healthy localities, and in Localities which are further away
      from CHS's hospitals. CONCLUSIONS: These findings indicate that the presence of
      the health funds in different Localities varies according to the Localities'
      characteristics. There appears to be a market segmentation and "specialization"
      of certain health funds in specific populations, and of the other health funds in
      the rest of the population.

PMID- 21939117
TI  - [Complementary and alternative medicine--time for research and regulation].
AB  - The usage of complementary and alternative medicine [CAM] is increasing in
      popularity in the modern world. In this issue of Harefuah, seven articles relate
      to various aspects of CAM: the use of various modalities of CAM in four community
      clinics in Northern Israel, an assessment of the needs and expectations of
      patients on chemotherapy from the integration of CAM in palliative oncological
      care, a description of a series of quality research studies relating to CAM in
      hemato-oncological disorders and autoimmune diseases and a discussion of ethical
      dilemmas and issues relating to Jewish law. Other authors review the history of
      clinical studies with an emphasis on mind-body connection and the placebo effect.
      The conclusion that may be derived about CAM from this compilation of articles is
      that, despite the ltack of scientific evidence to support the paradigm underlying
      most CAM modalities and the scarcity of evidence to support its efficacy, the
      increasing popularity of CAM should lead us to expand research into CAM and to
      teach our medical students about CAM. We should do so for the sake of proper
      doctor-patient relationships and to prevent improper use of CAM by the general
      public. The diversity of CAM modalities and the heterogeneity of training
      patterns among those who practice CAM call for the prompt regulation of training
      and licensing of all CAM practitioners.

PMID- 21939118
TI  - [Complementary medicine--the facts].
AB  - The popularity of complementary medicine in the western world continues to grow.
      Complementary medicine has a wide scope of topics including acupuncture,
      hypnosis, meditation, chiropractic manipulation, tai chi, yoga, botanical and
      herbal supplements and many other undefined modalities such as copper bracelets,
      magnets, holy water etc. For most modalities the mechanism of action is unknown
      and the evidence of benefit is poor. Some modalities such as acupuncture,
      hypnosis and tai chi may improve pain and other subjective complains. It seems
      that most of the beneficial effects of complementary medicine are placebo
      effects. Complementary treatment may be associated with side effects and should
      not be an alternative to the conventional medicine. Complementary medicine can be
      used as an adjunct to the conventional medicine and should be used in full
      agreement with and under the supervision of the attending physician. Patients
      should be informed about the existing evidence and what to expect from
      complementary medicine. Further meticulous research should be conducted to expand
      our knowledge in complementary medicine.

PMID- 21939119
TI  - [Novel psychotherapeutic methods and the role of mental health centers in their
      implementation].
AB  - In this issue of Harefuah, Arbel et at. describe the implementation of
      mindfulness-based psychotherapy IMBP) in the Beer Sheba Mental HeaLth Center. MBP
      is an example of a form of complementary and alternative medical treatment, which
      became widespread and is now considered both safe and efficient. It includes
      mindful sitting practice, developing awareness, mindful movement, psycho
      education, and often a cognitive component. MBP has a role in the treatment of
      minor and major mental disorders, and'may also alleviate stress and improve weLtl
      being among therapists. In the Beer Sheba Center, MBP courses were offered to all
      staff members, and MBP group treatment was started in one of the wards. The
      promising results of MBP's implementation will be evaluated. This project
      emphasizes the pivotal role of mental health centers in the teaching of students
      and residents in mental health. This role must be considered while planning the
      future of these centers in the current reform of Israel's psychiatric services.

PMID- 21939120
TI  - [Cholinergic anti-inflammatory pathway of some non-pharmacological therapies of
      complementary medicine: possible implications for treatment of rheumatic and
      autoimmune diseases].
AB  - Rheumatologic and autoimmune diseases are among foremost diseases for which
      patients seek complementary and integrative medicine options. Therefore,
      physicians should be informed on the advances in research of these therapies, in
      order to be able to discuss possible indications and contraindications for these
      treatment modalities with their patients. This review summarizes several
      therapeutic modalities of complementary medicine that may be involved in the
      cholinergic anti-inflammatory pathway. The analysis of systematic reviews of
      acupuncture for rheumatic conditions has concluded that the evidence is
      sufficiently sound to warrant positive recommendations of this therapy for
      osteoarthritis, low back pain and lateral elbow pain. There is relatively strong
      evidence to support the use of hypnosis in pain treatment, such as in cases of
      fibromyalgia. A recent controlled study that evaLuated tai-chi in fibromyalgia
      has reported reductions in pain, improvements in mood, quality of Life, self
      efficacy and exercise capacity. There is also cumulative evidence that
      acupuncture, hypnosis and tai-chi may decrease the high frequency of heart rate
      variability, suggesting enhancement of vagus nerve activity. Hence, it has been
      hypothesized that these modalities might impact the cholinergic anti-inflammatory
      pathway to modulate inflammation. Further clinical and basic research to confirm
      this hypothesis should be performed in order to validate integration of these
      therapies in comprehensive treatment for some inflammatory and autoimmune
      diseases.

PMID- 21939121
TI  - [Complementary medicine in hemato-oncology care: review of controlled clinical
      studies].
AB  - In this article, we review seven randomized controlled trials (RCTs) that studied
      efficacy and safety of complementary and alternative medicine (CAM) in hemato
      oncology care. The studies examined various CAM modalities in the treatment of
      general quality of life, mental, sleep, and gastro-intestinal symptoms. In
      addition, we reviewed in vitro and nonrandomized cLinical trials in herbal
      medicine and other CAM modalities. The authors recommend focusing future CAM
      studies on empowering patients in hemato-oncology care while monitoring efficacy
      and safety of treatment and avoiding harmful interaction with conventional care.

PMID- 21939122
TI  - [From Nebuchadnezzar to the randomized controlled trial--milestones in the
      development of clinical research].
AB  - The first clinical experiment is described in the bible: The prophet Daniel is
      reported being nourished during ten days by seeds and water only, in order to
      check if his physical state would deteriorate as a result of this minimal
      nutrition. In the 15th century, French surgeon Ambroise Pari experimented with a
      mixture of turpentine, egg protein and rose oil to treat combat wounds, which is
      thought to be the first clinical study to be reported. In the 19th century
      British scientist James Lind designed the first controlled prospective study with
      parallel groups, proving that ingesting citrus fruit prevents scurvy. A short
      time afterwards British scientist John Haygarth was the first to use a placebo
      drug in a clinical study. Important work on placebo was conducted by the American
      scientists Austin Flint and later by Henry K. Beecher, who showed that placebo
      itself has biological properties. The importance of comparative studies was first
      understood by French psychologist CLaude Bernard. He is considered the founder of
      the modern scientific method based on observation, analysis of data and
      examination of hypotheses. Bernard's work was based on the work of fellow
      Frenchman Pierre Charles Alexandre Louis, who is justly considered a founding
      father of modern epidemiology, and who was the first to use statistics in
      clinical experiments. Random distributions in clinical studies were reported even
      before this time, for instance in the work of the Flemish physician Johannes
      Baptista van Helmont. Danish Nobel prize winner Johannes Fibiger pioneered the
      use of selection bias in his work with diphtheria serum.

PMID- 21939123
TI  - [Complementary medicine--Jewish medical ethics].
AB  - In Israel, as in the Western world, the use of different methods of complementary
      and alternative medicine ICAM) is spreading. CAM raises ethical questions of
      concern to healthcare providers and to the public: Can physicians recommend a
      treatment that has no scientific evidence? Should the government include such
      therapies in the health budget? Can complementary therapists receive protection
      against lawsuits if their treatment is recognized? The purpose of this article is
      to present a Jewish perspective on these issues. The fundamental sources that
      deal with the subject are based on the approach of rabbinic authorities toward
      unproven medicine, as expressed in the "Mishnah" and "Talmud" (200-500 C.E). The
      great Jewish scholar who discusses the subject in detail is Maimonides (1135
      1204), who defines what "medicine" is and claims that medicine has to rely on
      reason or experience. Contemporary Jewish commentators present their position
      based on the interpretation of Maimonides' texts. In this article we claim that
      treatments can be divided into four groups, each group having a different
      halachic status: (1) Treatment that might be dangerous--should not be used. (2)
      Treatment that is safe--can be used, but has no other special status. (3)
      Treatment recognized by alternative therapists--has consequences for the
      observant Jew, such as laws of Kashrut and Shabbat. (4) Treatment that was tested
      and proven using modern medical methods has public significance--the therapist is
      entitled to legal defense if he made a reasonable mistake; the government can
      consider funding such treatment using public money. This article presents the
      Jewish halachic sources upon which we propose an ethical-practical approach to
      CAM.

PMID- 21939124
TI  - [Implementing mindfulness based therapies as part of the comprehensive treatments
      in the Beer Sheba Mental Health Center].
AB  - In recent years, there has been a growing interest and popularity in mindfulness
      based therapies. Theories and practices that, until lately, have been considered
      esoteric and practiced in private by only a few therapists, are now progressively
      becoming part of mainstream establishment therapies and are gaining greater
      interest and recognition. The therapies can be carried out either in an
      individual or in a group setting and most include formal mindful sitting
      practice, developing awareness, mindful movement, psycho-education and often
      include a cognitive component. Furthermore, these therapies are becoming
      increasingly validated by widespread research pointing to promising results in
      the treatment of various cLinicaL disorders including anxiety, depression and
      relapse prevention, personality disorders, attention disorders and psychotic
      disorders, in both an in-patient and out-patient setting. The aim of this
      overview is to describe the deveLopment that has taken place in the fast decades
      within the field of mindfulness-based therapies and to present the most up-to
      date research in this area: to show which therapeutic interventions have been
      proven to be effective; the background of the ideas; and the relevance of these
      approaches to the mental health system in Israel.

PMID- 21939125
TI  - [Tolerance to heat in burnt patients].
AB  - Body temperature regulated within the homeostatic range, is essential for the
      stability of the "milieu interieur" and for maintaining intact body functioning.
      Those individuals in the population who cannot adapt to heat stress and whose
      body temperature will rise earlier and at a higher rate than expected under
      predetermined conditions are considered as 'heat intolerant". Patients with deep
      burns are intolerant to heat because of the injured dermis and the destruction of
      the imbedded eccrine sweat glands and the peripheral vascular bed and its post
      synaptic innervations, which common treatment with split-thickness skin grafts
      cannot restore. Thus, the extent of the inability to regulate body temperature is
      associated with the percent of the burnt area - the Larger the affected area, the
      lower is the ability to thermoregulate. The cumulative data suggest that the
      state of heat intolerance in deep-burnt patients is a persisting condition and
      cannot be alleviated by heat acclimation.

PMID- 21939126
TI  - Adults behave better when teddy bears are in the room.

PMID- 21939127
TI  - How to solve the cost crisis in health care.
AB  - U.S. health care costs currently exceed 17% of GDP and continue to rise. One
      fundamental reason that providers are unable to reverse the trend is that they
      don't understand what it costs to deliver patient care or how those costs compare
      with outcomes. To put it bluntly, few health care providers measure the actual
      costs for treating a given patient with a given medical condition over a full
      cycle of care, or compare the costs they incur with the outcomes they achieve.
      What isn't measured cannot be managed or improved, and this is all too true in
      health care, where poor costing systems mean that effective and efficient
      providers go unrewarded, and inefficient ones have little incentive to improve.
      But all this can be remedied by exploring the concept of value in health care and
      carefully measuring costs. This article describes a new way to analyze costs that
      uses patients and their conditions--not organizational units or narrow diagnostic
      treatment groups--as the fundamental unit of analysis for measuring costs and
      outcomes. The new approach, called time-driven activity-cased costing, is
      currently being implemented in pilots at the Head and Neck Center at MD Anderson,
      the Cleft Lip and Palate Program at Children's Hospital in Boston, and units
      performing knee replacements at Schon Klinik in Germany and Brigham & Women's
      Hospital in Boston. As providers and payors better understand costs, they will be
      positioned to achieve a true "bending of the cost curve" from within the system,
      not in response to top-down mandates. Accurate costing also unlocks a whole
      cascade of opportunities, such as process improvement, better organization of
      care, and new reimbursement approaches that will accelerate the pace of
      innovation and value creation.

PMID- 21939128
TI  - A cancer center puts the new approach to work.

PMID- 21939129
TI  - Learning to live with complexity.
AB  - Business life has always featured the unpredictable, the surprising, and the
      unexpected. But in today's hyperconnected world, complexity is the norm. Systems
      that used to be separate are now intertwined and interdependent, and knowing the
      starting conditions is no guide to predicting outcomes; too many continuously
      changing interactive elements are in play. Managers looking to navigate these
      difficulties need to adopt new approaches. They should drop outmoded forecasting
      tools-for example, ones that rely on averages, which are often less important
      than outliers. Instead, they should use models that simulate the behavior of the
      system. They should also make sure that their data include a good amount of
      future-oriented information. Risk mitigation is crucial as well. Managers should
      minimize the need to rely on predictions-for instance, they can give users a say
      in product design. They can decouple elements in a system and build in redundancy
      to minimize the consequences of a partial system failure, and turn to outside
      partners to extend their own company's capabilities. They can complement hard
      analysis with "soft" methods such as storytelling to make potentially important
      future possibilities more real. And they can make trade-offs that keep early
      failures small and provide the diversity of thought needed in a nimble
      organization faced with complexity on virtually every front.

PMID- 21939130
TI  - Smart rules: six ways to get people to solve problems without you.
AB  - As the world has become more complex, companies have steadily increased their
      performance requirements: Now they strive to offer low prices and high quality;
      to customize products for local markets and standardize them for greater returns;
      to innovate and be efficient. The typical corporate response to such conflicting
      goals complicates things further: Firms restructure and try to align their
      organizations with extra coordinating functions, processes, and incentives. This
      approach does more harm than good. Managers' time gets sucked up by reports and
      meetings, leaving little time to work with employees. But there is a better way,
      says BCG senior partner Yves Morieux: Instead of strangling employees with new
      rules and procedures, create an environment in which they're compelled to work
      with one another to develop solutions to complex challenges. Managers can create
      this environment by applying six "smart rules": (1) improve understanding of what
      coworkers do and the real constraints they face, (2) determine which people are
      the firm's natural integrators and strengthen their roles, (3) expand the amount
      of power available to everyone, (4) increase the need for reciprocity in the
      system, (5) make employees feel the "shadow of the future," and (6) hold
      uncooperative people accountable. By tapping employees' ingenuity through the use
      of smart rules, firms can manage complexity quickly and creatively-and streamline
      their organizations.

PMID- 21939131
TI  - How to cultivate engaged employees.
AB  - Everybody knows that an empowered team enhances everyone's performance, including
      the manager's. Vlachoutsicos, of the Athens University of Economics and Business,
      argues that the vital, particular ingredient in buoying employees is fostering a
      sense of mutual dependence, or "mutuality," every time you interact with
      subordinates. He offers six lessons in achieving mutuality: 1. Be modest.
      Specifically, avoid talking about your track record and instead focus on your
      people's present needs. 2. Listen seriously--and show it. Don't assume that folks
      recognize how attentive you are. Make sure the outward signs reflect it. 3.
      Invite disagreement. But deliver the invitation artfully so that people really do
      pipe up. 4. Focus the agenda. Don't let discussion run amok in the name of
      openness. Streamline it so that the progress is palpable to all participants. 5.
      Don't try to have all the answers. See yourself more as a catalyst for problem
      solving than as a problem solver per se. 6. Don't insist that a decision must be
      made. Give the decision-making process time to breathe, even if that sometimes
      means delaying a conclusion. The author richly illustrates each of these lessons
      with a compelling story from his lifelong experience.

PMID- 21939132
TI  - Using a data-matrix-coded sponge counting system across a surgical practice:
      impact after 18 months.
AB  - BACKGROUND: Retained surgical items (RSIs), most commonly sponges, are
      infrequent. Yet despite sponge-counting standards, failure to maintain an
      accurate count is a common error. To improve counting performance, technology
      solutions have been developed. A data-matrix-coded sponge (DMS) system was
      evaluated and implemented in a high-volume academic surgical practice at Mayo
      Clinic Rochester (MCR). The primary end point was prevention of sponge RSIs after
      18 months. METHODS: Two trials were conducted before implementation. A randomized
      controlled trial assessed the system's function, efficiency, and ergonomics. The
      second, larger trial was conducted to validate the prior findings and test
      product improvements. After the trials, the system was implemented in all 128
      operating/procedure rooms across the MCR campus on February 2, 2009. The
      institutionwide implementation was intended to avoid the possibility of having
      standard unmarked sponges and DMSs in the operating room suite concurrently.
      RESULTS: Before implementation, a retained sponge occurred on average every 64
      days. Between February 2009 and July 2010, 87,404 procedures were performed, and
      1,862,373 DMSs were used without an RSI (p < .001). After four cases, the average
      time to count a DMS decreased from 11 to 4 seconds. Total sponge counting
      time/operation increased without any increase in overall operative time.
      CONCLUSIONS: After 18 months, a DMS system eliminated sponge RSIs from a high
      volume surgical practice. The DMS system caused no work-flow disruption or
      increases in case duration. Staff satisfaction was acceptable, with a high degree
      of trust in the system. The DMS system is a reliable and cost-effective
      technology that improves patient safety.

PMID- 21939133
TI  - A strategic approach for managing conflict in hospitals: responding to the Joint
      Commission leadership standard, Part 1.
AB  - BACKGROUND: The Joint Commission's leadership standard for conflict management in
      hospitals, LD.02.04.01, states, "The hospital manages conflict between leadership
      groups to protect the quality and safety of care." This standard is one of
      numerous standards and alerts issued by The Joint Commission that address
      conflict and communication. They underscore the significant impact of relational
      dynamics on patient safety and quality of care and the critical need for a
      strategic approach to conflict in health care organizations. Whether leadership
      conflicts openly threaten a major disruption of hospital operations or whether
      unresolved conflicts lurk beneath the surface of daily interactions, unaddressed
      conflict can undermine a hospital's efforts to ensure safe, high-quality patient
      care. DEVELOPING A STRATEGIC APPROACH TO CONFLICT MANAGEMENT: How leaders manage
      organizational conflict has a significant impact on achieving strategic
      objectives. Aligning conflict management approaches with quality and safety goals
      is the first step in adopting a strategic approach to conflict management. A
      strategic approach goes beyond reducing costs of litigation or improving
      grievance processes--it integrates a collaborative mind-set and individual
      conflict competency with nonadversarial processes. UNDERTAKING A CONFLICT
      ASSESSMENT: Conflict assessment should determine how conflicts are handled among
      the leaders at the hospital, the degree of conflict competence already present
      among the leaders, where the most significant conflicts occur, and how leaders
      think a conflict management system might work for them. CONCLUSIONS:
      Strategically aligning a conflict management approach that addresses conflict
      among leadership groups as a means of protecting the quality and safety of
      patient care is at the heart of LD.02.04.01.

PMID- 21939134
TI  - A strategic approach for managing conflict in hospitals: responding to the Joint
      Commission leadership standard, Part 2.
AB  - BACKGROUND: A well-designed conflict management process for hospital leaders
      should both retain the positive benefits of constructive conflict engagement and
      minimize the adverse consequences that unmanaged conflict can have on patient
      care. Dispute system design (DSD) experts recommend processes that emphasize the
      identification of the disputing parties' interests and that avoid reliance on
      exertions of power or resort to rights. In an emerging trend in designing
      conflict management systems, focus is placed on the relational dynamics among
      those involved in the conflict, in recognition of the reciprocal impact that each
      participant in a conflict has on the other. The aim is then to restore trust and
      heal damaged relationships as a component of resolution. COMPONENTS OF THE
      CONFLICT MANAGEMENT PROCESS: The intent of Standard LD.02.04.01 is to prevent
      escalation to formal legal disputes and encourage leaders to overcome their
      conflict-avoidance tendencies through the use of well-designed approaches that
      support engagement with conflict. The sequence of collaborative options consists
      of individual coaching and counseling; informal face-to-face meetings; informal,
      internally facilitated meetings; informal, externally facilitated meetings;
      formal mediation; and postdispute analysis and feedback. CONCLUSIONS: Every
      hospital has unique needs, and every conflict management process must be tailored
      to individual circumstances. The recommendations in this two-part article can be
      adapted and incorporated in other, more comprehensive conflict management
      processes throughout the hospital. Expanding the conflict competence of leaders
      to enable them to effectively engage in and model constructive conflict-handling
      behaviors will further support the strategic goal of providing safe and effective
      patient care.

PMID- 21939135
TI  - The cost of serious fall-related injuries at three Midwestern hospitals.
AB  - BACKGROUND: Consequences of fall-related injuries can be both physically and
      financially costly, yet without current data, hospitals cannot completely
      determine the financial cost. As part of the analysis for an initiative to
      minimize falls with injury, the cost and length of stay attributable to serious
      fall injury were estimated at three hospitals in a Midwestern health care system
      METHODS: In a retrospective case-control study, 57 hospital inpatients discharged
      between January 1, 2004, and October 16, 2006, who sustained a serious fall
      related injury (fracture, subdural hematoma, any injury resulting in surgical
      intervention, or death) were identified through the incident reporting system and
      matched to nonfaller inpatient controls by hospital, age within five years, year
      of discharge, and diagnosis-related group (DRG). RESULTS: Multivariate analyses
      indicated that operational costs for fallers with serious injury, as compared
      with controls, were $13,316 more (p < .01; 95% confidence interval [CI], $1,395
      $35,561) and that fallers stayed 6.3 days longer than nonfallers (p < .001; 95%
      CI, 2.4-14.9). Univariate analyses indicated they were also significantly more
      likely to have diabetes with organ damage, moderate to severe renal disease, and
      a higher mean score on the Charlson Comorbidity Index. In optimal bipartite
      matching (OBM) analyses, fallers with serious injury cost $13,806 more (p < .001;
      95% CI, $5,808-$29,450) and stayed 6.9 days longer (p < .001; 95% CI, 2.8-14.9).
      CONCLUSIONS: Hospital inpatients who sustained a serious fall-related injury had
      higher total operational costs and longer lengths of stay than nonfallers.
      Despite possible limitations regarding the cost allocation methods, the analysis
      included data from three different hospitals, and supplemental multivariate
      analyses adjusting for academic hospital status did not meaningfully affect the
      results.

PMID- 21939136
TI  - Trainees' perceptions of patient safety practices: recounting failures of
      supervision.
AB  - BACKGROUND: Ensuring that trainees receive appropriate clinical supervision is
      one proven method for improving patient safety outcomes. Yet, supervision is
      difficult to monitor, even more so during advanced levels of training. The manner
      in which trainees' perceived failures of supervision influenced patient safety
      practices across disciplines and various levels of training was investigated.
      METHODS: A brief, open-ended questionnaire, administered to 334 newly hired
      interns, residents, and fellows, asked for descriptions of situations in which
      they witnessed a failure of supervision and their corresponding response.
      RESULTS: Of the 265 trainees completing the survey, 73 (27.5%) indicated having
      witnessed a failure of supervision. The analysis of these responses revealed
      three types of supervision failures-monitoring, guidance, and feedback. The
      necessity of adequate supervision and its accompanying consequences were also
      highlighted in the participants responses. CONCLUSIONS: The findings of this
      study identify two primary sources of failures of supervision: supervisors'
      failure to respond to trainees' seeking of guidance or clinical support and
      trainees' failure to seek such support. The findings suggest that the learning
      environment's influence was sufficient to cause trainees to value their
      appearance to superiors more than safe patient care, suggesting that trainees'
      feelings may supersede patients' needs and jeopardize optimal treatment. The
      literature on the impact of disruptive behavior on patient care may also improve
      understanding of how intimidating and abusive behavior stifles effective
      communication and trainees' ability to provide optimal patient care. Improved
      supervision and communication within the medical hierarchy should not only create
      more productive learning environments but also improve patient safety.

PMID- 21939137
TI  - [Not a good sign. Firm nodules in the skin].

PMID- 21939138
TI  - [Development of diabetes requires preventive action. "It is our goal to cure
      diabetes" (interview by Wolfgang van den Bergh, Wolfgang Geissel and Helmut
      Laschet)].

PMID- 21939139
TI  - [What should be relayed to your patients. A plastic surgery intervention is not a
      visit to the hair dresser (interview by Dr. Beate Fessler)].

PMID- 21939140
TI  - [Diabetic neuropathy. What do the guidelines recommend?].

PMID- 21939141
TI  - [Naturopathy consultation. Tonsillitis].

PMID- 21939142
TI  - [Diagnostic uncertainty: irritable bowel syndrome in general practice].

PMID- 21939143
TI  - [Rational clinical decision making in general practice: chest pain].

PMID- 21939144
TI  - [Diagnostic procedures in patients with acute and chronic cough--recommendations
      for general practice].

PMID- 21939145
TI  - [The unintentional weight loss--what is to do in general practice?].

PMID- 21939146
TI  - [Emergency checklist: acute lymphangitis].

PMID- 21939147
TI  - [Bladder cancer--symptoms and diagnosis].

PMID- 21939148
TI  - [Home blood pressure monitoring for diagnosis and treatment. From guidelines to
      optimal practice].

PMID- 21939149
TI  - [Bioflavonoids (1). Plant combination alleviates nasal obstruction].

PMID- 21939150
TI  - [Why chronic pain patients should see a pain specialist. "Chronic pain is an
      independent disorder"].

PMID- 21939151
TI  - A home care visit with Congresswoman Lynn Jenkins.

PMID- 21939152
TI  - Key strategies for success: highlights from the 17th Annual Financial Management
      Conference & Exposition.

PMID- 21939153
TI  - Effective use of technology to engage both patients and provider partners.

PMID- 21939154
TI  - Medication reconciliation.

PMID- 21939155
TI  - Pharmacists become an integral part of the patient care team.

PMID- 21939156
TI  - Mayor William Martin, RN: caring for the community he loves.

PMID- 21939157
TI  - Back to the basics.

PMID- 21939158
TI  - Paying for long-term in-home care.

PMID- 21939159
TI  - A country fair and quantum theory.

PMID- 21939160
TI  - CEOs and saints: leadership lessons from Mother Teresa.

PMID- 21939161
TI  - Cardiovascular risk factors: the many few.

PMID- 21939162
TI  - Plasmodium knowlesi malaria in Malaysia.
AB  - Plasmodium knowlesi, a simian malaria parasite, is now recognised as the fifth
      cause of human malaria and can lead to fatal infections in humans. Knowlesi
      malaria cases are widely distributed in East and West Malaysia and account for
      more than 50% of admissions for malaria in certain hospitals in the state of
      Sarawak. This paper will begin with a description of the early studies on P.
      knowlesi, followed by a review of the epidemiology, diagnosis, clinical and
      laboratory features, and treatment of knowlesi malaria.

PMID- 21939163
TI  - Prevalence of cardiovascular disease risk factors among attendees of the Batu 9,
      Cheras Health Centre, Selangor, Malaysia.
AB  - This study describes the prevalence of selected cardiovascular disease (CVD) risk
      factors screened in patients 30 years and above attending a health centre in
      Cheras, Selangor. The study involved 3772 patients screened from March 2002 to
      June 2008. Risk factors screened included blood pressure, height, weight, serum
      total cholesterol, random blood sugar levels and smoking status. Majority of
      respondents were between 40 and 49 years of age (58.1%), males (64.7%) and ethnic
      Malays (74.4%). About two thirds (62.6%) were found to be overweight or obese,
      two fifths (40.2%) had hypercholesterolemia, a third (34.2%) had hypertension and
      31.6% were smokers at some time. Overall 87% and 60% had at least one and two CVD
      risk factors respectively. Prevalence of four of the five risk factors screened
      was highest among the Malay middle aged men and lowest among the Chinese. Thus a
      substantial proportion of middle aged men were at high risk of CVD. Our findings
      show the need for ongoing monitoring of CVD risk factors and implementation of
      effective preventive strategies.

PMID- 21939164
TI  - Prevalence of diabetes in the Malaysian National Health Morbidity Survey III
      2006.
AB  - The Malaysian National Health Morbidity Survey III (NHMS III), conducted in 2006,
      was a cross-sectional household survey of the prevalence of chronic diseases,
      involving 34,539 respondents of age > or =18 years old, in all states of
      Malaysia. Data collection was by face-to-face interview. Those who self-professed
      not to be diabetics underwent finger-prick glucose test following at least 8
      hours of fasting. The overall prevalence of diabetes mellitus (known and newly
      diagnosed) was 11.6%. The Indians had the highest prevalence of 19.9% followed by
      Malays 11.9% and Chinese 11.4%. The prevalence of people with known diabetes and
      newly diagnosed diabetes was 7.0% and 4.5% respectively. Impaired Fasting
      Glycaemia was found to be 4.2%. Majority (73.5%) of the patients used government
      healthcare facilities for their diabetic care. Usage of insulin alone or in
      combination was low at 7.2% of patients. Only 45.05% of known diabetics have ever
      had their eye examined. Amputees formed 4.3% of the patients with known diabetes
      while 3.4% had suffered a stroke event and 1.6% was on some form of renal
      replacement therapy.

PMID- 21939165
TI  - A survey on the initial management of spontaneous pneumothorax.
AB  - Spontaneous pneumothorax (SP) is a common medical condition but continues to be a
      frequent management problem among doctors. Despite the availability of guidelines
      on management of SP, studies have shown that the compliance with the guidelines
      is low. The various treatment options available in treating this condition
      further confuse doctors on the right approach in managing SP. The objective of
      this study is to investigate the awareness of the availability of these existing
      guidelines and to investigate how the doctors involved in the initial management
      of SP would manage this condition. A self completed questionnaire which included
      three case scenarios were distributed among doctors in two teaching university
      hospitals and two large Ministry of Health hospitals. This study showed that
      there is a lack of awareness of the existing guidelines even among the senior
      doctors and there is a variation in the initial management of SP. Therefore a
      locally produced guideline may be beneficial to standardise and improve the
      management of SP.

PMID- 21939166
TI  - An analysis of forensic entomological specimens by Universiti Kebangsaan
      Malaysia.
AB  - This study reviews forensic entomological specimens analysed by the Department of
      Parasitology & Medical Entomology, Universiti Kebangsaan Malaysia for the year
      2004. A total of 10 cases (6 males and 4 females) were observed for the
      entomological specimens. Various types of death scenes were obtained including
      indoor and outdoor area such as bushes field, rubbish dumping site, and aquatic
      areas. Identified fly species collected from the death sites were blow flies,
      Chrysomya megacephala, Chrysomya rufifacies and Lucilia cuprina and unknown
      sarcophagid larvae, with Ch. megacephala being the most common species found in
      the ecologically varied death scene habitats. The post-mortem interval (PMI)
      estimation ranged from one to five days, based on the entomological specimens
      collected.

PMID- 21939167
TI  - Congenital cholesteatoma: delayed diagnosis and its consequences.
AB  - This is a retrospective review of congenital cholesteatoma cases that were
      managed surgically. There were 5 cases. The age of presentation ranged from 5 to
      18 year old. Three patients presented with complication of the disease. Three
      patients had intact tympanic membrane, two had perforation at the anterior
      superior quadrant. All patients had cholesteatoma medial to tympanic membrane.
      Four cases had extensive ossicular erosion with preoperative hearing worse than
      40 dB. Four cases underwent canal wall down mastoid surgery and one underwent
      canal wall up surgery. One patient had recurrence which required revision
      surgery. In conclusion, congenital cholesteatoma presented late due to the silent
      nature of disease in its early stage. Extensive disease, ossicular destruction
      with risk of complication at presentation were marked in our study. Hence, more
      aggressive surgical intervention is recommended in the management of congenital
      cholesteatoma.

PMID- 21939168
TI  - Executive function and attention span in euthymic patients with bipolar 1
      disorder.
AB  - This is a cross sectional comparison study to assess executive function and
      attention span in euthymic patients with bipolar 1 disorder. It compares the
      performance of these two cognitive domains in 40 patients with bipolar 1 disorder
      to that of 40 healthy normal subjects using Trail Making (TMT), Digit Span
      (Forward and Backward) and Verbal Fluency (VF) tests. The association between
      demographic, clinical characteristics and performance in all tests were examined.
      Patients with bipolar illness showed significant impairment with moderate to
      large effect sizes (VF = 0.67, TMT A = 0.52, TMT B = 0.81, Digit Forward = 0.97,
      Digit backward = 1.10) in all tasks of executive and attention functioning. These
      impairments are observed in the absence of active mood symptoms while duration
      and severity of illness are not found to have an effect on both cognitive
      domains. Medications received by patients with bipolar disorder have significant
      association with performance on executive tasks. The results of this study add on
      to the existing global evidence of cognitive impairment in bipolar illness
      despite its cross cultural differences. Its presence in the absence of mania,
      depression or mixed episode indicates that cognitive impairment is stable even
      after symptoms recovery.

PMID- 21939169
TI  - Review of advantages of Joel-Cohen surgical abdominal incision in caesarean
      section: a basic science perspective.
AB  - Caesarean section is a common operation and the best postoperative outcomes are
      desired. Surgical techniques have been devised or modified to reduce operative
      and post operative discomfort. Many studies have evaluated or compared the Joel
      Cohen abdominal incision with Pfannenstiel incision and found the former to be
      superior for various reasons such as less postoperative febrile morbidity, less
      analgesia requirements, shorter operating time, less intra operative blood loss
      and adhesion formation, reduction in hospital stay and wound infection in the
      group undergoing Caesarean section by this technique. This study is to find
      whether better postoperative outcomes of the Joel-Cohen incision group can be
      justified by the explanations of fundamentals of the basic sciences. Literature
      was reviewed for randomized clinical trials and review articles comparing the
      different kinds of abdominal incisions for Caesarean section. The study revealed
      that the Joel-Cohen method was beneficial. The fundamentals of basic sciences
      were studied to try to find an explanation to the enumerated advantages of the
      Joel-Cohen procedure; attributing to the differences in the techniques used.

PMID- 21939170
TI  - Mesenchymal stem cells inhibit proliferation of lymphoid origin haematopoietic
      tumour cells by inducing cell cycle arrest.
AB  - We have previously shown that mesenchymal stem cells (MSC) inhibit tumour cell
      proliferation, thus promising a novel therapy for treating cancers. In this
      study, MSC were generated from human bone marrow samples and characterised based
      on standard immunophenotyping. When MSC were co-cultured with BV173 and Jurkat
      tumour cells, the proliferation of tumour cells were profoundly inhibited in a
      dose dependent manner mainly via cell to cell contact interaction. Further cell
      cycle analysis reveals that MSC arrest tumour cell proliferation in G0/G1 phase
      of cell cycle thus preventing the entry of tumour cells into S phase of cell
      cycle.

PMID- 21939171
TI  - Partial deletion 9p syndrome in Malaysian children.
AB  - We report the first two Malaysian children with partial deletion 9p syndrome, a
      well delineated but rare clinical entity. Both patients had trigonocephaly,
      arching eyebrows, anteverted nares, long philtrum, abnormal ear lobules,
      congenital heart lesions and digital anomalies. In addition, the first patient
      had underdeveloped female genitalia and anterior anus. The second patient had
      hypocalcaemia and high arched palate and was initially diagnosed with DiGeorge
      syndrome. Chromosomal analysis revealed a partial deletion at the short arm of
      chromosome 9. Karyotyping should be performed in patients with craniostenosis and
      multiple abnormalities as an early syndromic diagnosis confers prognostic,
      counselling and management implications.

PMID- 21939172
TI  - Mucosal malignant melanoma of the maxillary sinus.
AB  - Mucosal malignant melanoma (MMM) is an aggressive tumour occurring in the upper
      respiratory tract. It is rare compared to malignant melanoma of the skin. We
      report a case of a 53-year-old man with left paranasal swelling. A biopsy showed
      high-grade spindle cell tumour. Subsequently a subtotal maxillectomy was
      performed. Histopathological examination revealed a hypercellular tumour composed
      of mixed spindle and epitheloid cells with very occasional intracytoplasmic
      melanin pigment. The malignant cells were immunopositive for vimentin, S-100
      protein and HMB-45. It was diagnosed as mucosal malignant melanoma (MMM). This
      article illustrates a rare case of MMM where the diagnosis may be missed or
      delayed without proper histopathological examination that include meticulous
      search for melanin pigment and appropriate immunohistochemical stains to confirm
      the diagnosis. Malignant melanoma can mimic many other types of high-grade
      malignancy and should be considered as a differential diagnosis in many of these
      instances.

PMID- 21939173
TI  - Antiphospholipid syndrome with pulmonary artery embolism and multiple venous
      thromboses.
AB  - We report a case of a 21-year-old university student with underlying lupus
      nephritis who presented with recurrent symptoms of fever, haemoptysis, and
      pleuritic chest pain. CT pulmonary angiogram confirmed pulmonary embolism in the
      right subsegmental pulmonary arteries. One week later, she developed left renal
      vein and left common iliac vein thromboses, with new emboli in the left
      subsegmental pulmonary arteries. We hereforth discuss the diagnostic issues of a
      patient with systemic lupus erythematosus (SLE) on corticosteroids therapy, and
      also treatment of the antiphospholipid syndrome.

PMID- 21939174
TI  - Orbital myxoma--an unusual cause of inferoorbital mass.
AB  - To describe a case of isolated infraorbital mass which had been present for the
      past 9 years in a young woman. Despite the size, the mass was successfully
      excised in total. METHOD: Case report. RESULT: Histologically, the tumour was
      found to be an isolated orbital myxoma. CONCLUSION: Isolated orbital myxoma is an
      exceedingly rare tumour of the orbit. The case shows the lesion could be excised
      in its entirety with good cosmetic result.

PMID- 21939175
TI  - Recurrent multiple myeloma presenting as a breast plasmacytoma.
AB  - We describe a patient with multiple myeloma, who initially responded to
      chemotherapy and went into remission. She presented 10 months later with a right
      breast lump which was confirmed by core biopsy to be a plasmacytoma. Further
      treatment with radiotherapy, thalidomide and later second line chemotherapy
      appeared unsuccessful and she showed rapid disease progression with rising
      paraproteins and new extramedullary plasmacytoma lesions in the forehead,
      supraclavicular region, nasopharynx, liver, spleen, pancreas and paraaortic lymph
      nodes.

PMID- 21939176
TI  - Proptosis: a rare presentation of metastatic renal cell carcinoma.
AB  - We present a case of a middle-aged man who was incidentally found to have right
      renal solid mass while investigating for his left eye proptosis. Computerised
      tomography (CT) scan confirmed the diagnosis of renal cell carcinoma and the
      tumour was successfully excised via open surgery. The histopathology examination
      revealed the 10x7x8 cm mass to be a clear cell type renal cell carcinoma. The
      rare presentation of this metastatic renal cell carcinoma, its diagnosis and
      management will be discussed.

PMID- 21939177
TI  - Fundamentals in the management of multiple myeloma.
AB  - Progress in our understanding of multiple myeloma and its treatment has resulted
      in a more tailored approach to patient management, with different therapeutics
      regimens for different patient populations. The decision to initiate therapy
      depends primarily on the presence of symptoms which has to balance the chance of
      tumor clearance and against the risks of treatment related mortality. Selection
      of appropriate initial treatment should be based primarily on patient's
      characteristics (biologic age, co-morbidities), the disease characteristics
      (tumor burden and genetic risk profile) and the expected toxicity profile of the
      different regimens. When treatment begins, in younger transplant eligible
      patients the goal is to achieve high quality responses with intensive therapies
      as the quality of response appears to be important surrogates for long-term
      outcome. In the majority of myeloma patients in whom intensive treatment is not
      an option due to advanced age and co-morbidities, treatment should emphasize on
      optimal disease control to obtain symptomatic relief and to maintain a
      satisfactory quality of life. The introduction of novel agents has substantially
      changed the treatment paradigm of this otherwise incurable disease. The
      utilization of these drugs has moved from relapse setting to the front line
      setting and has benefited all patient groups. Because of these rapid developments
      and many treatment options we need good quality clinical studies to guide
      clinical practice in the management of patients with multiple myeloma. This
      review presents an update on current concepts of diagnosis and treatment of
      patients with multiple myeloma and provides recommendations on tailored therapies
      with particular reference to the local practice. The information presented herein
      may be used by the health care providers caring for myeloma patients as a
      guideline to counsel patients to understand their disease and the treatment
      better.

PMID- 21939178
TI  - Metal azolate frameworks: from crystal engineering to functional materials.

PMID- 21939179
TI  - Contactless measurement of surface dominated recombination in gold- and aluminum
      catalyzed silicon vapor-liquid-solid wires.
AB  - Carrier lifetimes of Si micro/nanowires grown by the vapor-liquid-solid method
      are measured using an extension of the classic contactless photoconductivity
      decay method. The samples measured consist of a thin aggregated film of oxide
      passivated wires on a fused silica carrier. Au catalyzed wires in the 392-730 nm
      diameter range are studied. Recombination in these wires is controlled by the
      surface or near surface effects, not bulk Au impurities. The lifetimes of Au- and
      Al-catalyzed wires of comparable diameter are measured. The Al wires are found to
      have slightly longer lifetimes than those grown with Au at a comparable diameter.
      Across all samples, the lifetimes measured range was from 0.2 to 1.0 ns. The
      surface controlled nature of the recombination measured implies larger diameter
      wires will offer better performance in devices that rely on minority carrier
      transport.

PMID- 21939181
TI  - C-H arylation of pyridines: high regioselectivity as a consequence of the
      electronic character of C-H bonds and heteroarene ring.
AB  - We report a new catalytic protocol for highly selective C-H arylation of
      pyridines containing common and synthetically versatile electron-withdrawing
      substituents (NO(2), CN, F and Cl). The new protocol expands the scope of
      catalytic azine functionalization as the excellent regioselectivity at the 3- and
      4-positions well complements the existing methods for C-H arylation and Ir
      catalyzed borylation, as well as classical functionalization of pyridines.
      Another important feature of the new method is its flexibility to adapt to
      challenging substrates by a simple modification of the carboxylic acid ligand or
      the use of silver salts. The regioselectivity can be rationalized on the basis of
      the key electronic effects (repulsion between the nitrogen lone pair and
      polarized C-Pd bond at C2-/C6-positions and acidity of the C-H bond) in
      combination with steric effects (sensitivity to bulky substituents).

PMID- 21939182
TI  - Antinociceptive properties of bergenin.
AB  - Bergenin (1) is a C-glucoside of 4-O-methylgallic acid with known antiarthritic
      activity attributed to modulation of cytokine production. The present study was
      undertaken to evaluate whether 1 has antinociceptive properties in models of
      inflammatory pain and to investigate its possible mechanisms of action.
      Pretreatment with 1 (12.5-100 mg/kg, ip) produced a dose-related inhibition of
      acetic acid-induced writhing in mice. Furthermore, treatment with 1 (50 and 100
      mg/kg) inhibited both the early and late phases in a formalin test. In addition,
      1 (50 and 100 mg/kg, ip) inhibited mechanical hyperalgesia, edema, and paw
      production of hyperalgesic cytokines (TNF-alpha and IL-1beta) induced by complete
      Freund's adjuvant. However, the local production of IL-10, an anti-inflammatory
      cytokine, was not altered by 1 (100 mg/kg, ip). Treatment with 1 produced a
      similar profile of antinociception in wild-type and IL-10-deficient mice. Mice
      treated with 1 did not show any motor performance alterations or apparent
      systemic toxicity. The results presented herein demonstrate that bergenin has
      consistent antinociceptive and anti-inflammatory properties, acting by the
      inhibition of IL-1beta and TNF-alpha production, and suggest its potential for
      the control of inflammatory pain.

PMID- 21939183
TI  - O,O'-Disubstituted N,N'-dihydroxynaphthalenediimides (DHNDI): first principles
      designed organic building blocks for materials science.
AB  - N,N'-Disubstituted naphthalenediimides (NDIs), planar, electron-deficient
      building blocks, play an important role in materials and biological sciences.
      Naphthalene core substituents control the HOMO and LUMO energies, whereas the N
      alkyl or aryl substituents affect the solubility, aggregation, and packing
      propensity in condensed phases. N,N'-Dihydroxynaphthalenediimide (DHNDI) allows
      expanding the chemical diversity by O-alkylation, acylation, or sulfonylation;
      these derivatives also allow fine-tuning of the HOMO/LUMO levels. The synthesis,
      UV-vis, electrochemical, solid state, and computational prediction of the
      properties of such derivatives are presented.

PMID- 21939184
TI  - Mechanistic study on the fluorination of K[B(CN)4] with ClF enabling the high
      yield and large scale synthesis of K[B(CF3)4] and K[(CF3)3BCN].
AB  - The fluorination of K[B(CN)(4)] with ClF is studied by millimolar test reactions
      in aHF and CH(2)Cl(2) solution and by subsequent identification of intermediates
      such as B-CF?NCl, B-CF(2)-NCl(2), and B-CF(3) species as well as NCl(3) by (19)F,
      (11)B NMR, and Raman spectroscopy, respectively. At first one cyano group of
      K[B(CN)(4)] is converted fast into a CF(3) group, and with increasing
      fluorination the reaction becomes slower and several intermediates could be
      observed. On the basis of these results, a synthesis was developed for
      K[B(CF(3))(4)] on a 0.2 molar scale by treatment of K[B(CN)(4)] diluted in aHF
      with ClF. The course of the reactions was followed by (i) monitoring the vapor
      pressure inside the reactor, (ii) observing the heat dissipation during ClF
      uptake, and (iii) measuring the volume of the released nitrogen gas. Since the
      fluorination of the last cyano group proceeds very slowly, the selective
      synthesis of K[(CF(3))(3)BCN] on a 0.2 molar scale is possible, as well. The
      analysis of the mechanisms, thermodynamics, and kinetics of the fluorination
      reactions is supported by density functional theory (DFT) calculations.

PMID- 21939185
TI  - Exploring the metal coordination properties of the pyrimidine part of purine
      nucleobases: isomerization reactions in heteronuclear Pt(II)/Pd(II) of 9
      methyladenine.
AB  - The synthesis and characterization of three heteronuclear Pt(2)Pd(2) (4, 5) and
      PtPd(2) (6) complexes of the model nucleobase 9-methyladenine (9-MeA) is
      reported. The compounds were prepared by reacting [Pt(NH(3))(3)(9-MeA
      N7)](ClO(4))(2) (1) with [Pd(en)(H(2)O)(2)](ClO(4))(2) at different ratios r
      between Pt and Pd, with the goal to probe Pd(II) binding to any of the three
      available nitrogen atoms, N1, N3, N6 or combinations thereof. Pd(II) coordination
      occurs at N1 and at the deprotonated N6 positions, yet not at N3. 4 and 5 are
      isomers of [{(en)Pd}(2){N1,N6-9-MeA(-)-N7)Pt(NH(3))(3)}(2)](ClO(4))(6).nH(2)O,
      with a head-head orientation of the two bridging 9-MeA(-) ligands in 4 and a head
      tail orientation in 5. 6 is [{(en)Pd}(2)(OH)(N1,N6-9MeA(-)
      N7)Pt(NH(3))(3)](ClO(4))(4).4H(2)O, hence a condensation product between
      [Pt(NH(3))(3)(9-MeA-N7)](2+) and a MU-OH bridged dinuclear (en)Pd-OH-Pd(en) unit,
      which connects the N1 and N6 positions of 9-MeA(-) in an intramolecular fashion.
      4 and 5, which slowly interconvert in aqueous solution, display distinct
      structural differences such as significantly different intramolecular Pd...Pd
      contacts (3.124 0(16) A in 4; 2.986 6(14) A in 5), among others. Binding of
      (en)Pd(II) to the exocyclic N6 atom in 4 and 5 is accompanied by a large movement
      of Pd(II) out of the 9-MeA(-) plane and a trend to a further shortening of the C6
      N6 bond as compared to free 9-MeA. The packing patterns of 4 and 5 reveal
      substantial anion-pi interactions.

PMID- 21939186
TI  - Cs4UGe8O20: a tetravalent uranium germanate containing four- and five-coordinate
      germanium.
AB  - A very rare tetravalent uranium germanate has been synthesized under hydrothermal
      conditions at 585  degrees C and 160 MPa. Its structure contains layers of single
      ring Ge(3)O(9)(6-) germanate anions that are connected by UO(6) octahedra and
      dimers of edge-sharing GeO(5) trigonal bipyramids to form a three-dimensional
      framework with intersecting 6- and 7-ring channels. UV-visible,
      photoluminescence, and U 4f X-ray photoelectron spectroscopy were used to confirm
      the valence state of uranium.

PMID- 21939187
TI  - Synthesis of an NDPK phosphocarrier domain peptide containing a novel
      triazolylalanine analogue of phosphohistidine using click chemistry.
AB  - Click phosphorylation of a propargylated unprotected peptide and phosphoryl azide
      using chaotrope-assisted Cu(I)-catalyzed 1,3-dipolar cycloaddition enabled a high
      yielding and rapid synthesis of a nucleoside diphosphate kinase (NDPK)
      phosphocarrier domain. The synthesis showcases a valuable synthetic platform for
      the synthesis of biologically relevant phosphopeptide analogues.

PMID- 21939188
TI  - 6-Phosphoryl picolinic acids as europium and terbium sensitizers.
AB  - Three 6-phosphoryl picolinic acid (6PPA) derivatives were synthesized and used as
      europium and terbium sensitizers. Two of the three ligands (6-diethoxyphosphoryl
      picolinic acid (Hdeppa) and 6-monoethoxyphosphoryl picolinic acid (H(2)meppa))
      are water-soluble, once complexed to lanthanide ions, while the third (6
      dihydroxyphosphoryl picolinic acid (H(3)dhppa)) forms a precipitate. The
      stability constants of the phosphoryl-based complexes were found to be higher
      than the carboxylate analogue (dipicolinic acid, H(2)dpa). The main species are
      the [LnL(3)] complexes under strict stoichiometric conditions, confirmed by (31)P
      NMR spectroscopy, mass spectrometry and lifetime analyses. The photophysical
      measurements reveal that the emission intensity of [Eu(deppa)(3)] is maximal at
      pH 4.8, whereas for [Eu(meppa)(3)](3-), the optimum pH is observed at 9.0. The
      lifetimes are all in the millisecond range and have confirmed the absence of
      water molecules in the first coordination sphere. The emissions of the terbium
      are always brighter than the corresponding europium within this phosphoryl
      series. The quantum yields of the phosphoryl containing complexes are lower than
      the carboxylate analogue ([Ln(dpa)(3)](3-)), except for [Tb(deppa)(3)], which
      exhibits an interesting quantum yield of 40% in aqueous solution.

PMID- 21939189
TI  - Reactivity of novel N,N'-diphosphino-silanediamine-based rhodium(I) derivatives.
AB  - The coordination abilities of the novel N,N'-diphosphino-silanediamine ligand of
      formula SiMe(2)(NtolPPh(2))(2) (SiNP, 1) have been investigated toward rhodium,
      and the derivatives [RhCl(SiNP)](2) (2), [Rh(SiNP)(COD)][BF(4)] (3), and
      Rh(acac)(SiNP) (4) have been synthesized. The stability of the dinuclear frame of
      [RhCl(SiNP)](2) (2) toward incoming nucleophiles has been shown to be dependent
      on their pi-acceptor ability. Indeed, the mononuclear complexes RhCl(SiNP)(L) (L
      = CO, 5; CN(t)Bu, 6) have been isolated purely and quantitatively upon reaction
      of 2 with CO and CN(t)Bu, respectively. Otherwise, PPh(3) and RhCl(SiNP)
      equilibrate with Rh(Cl)(SiNP)(PPh(3)) (7). Carbon electrophiles such as MeI and 3
      chloro-1-proprene afforded the oxidation of rhodium(I) to rhodium(III) and the
      formation of RhCl(2)(eta(3)-C(3)H(5))(SiNP) (8) and Rh(Me)(I)(SiNP)(acac) (10),
      respectively. The methyl derivative 10 is thermally stable and does not react
      either with CO or with CN(t)Bu even in excess. Otherwise, RhCl(2)(eta(3)
      C(3)H(5))(SiNP) (8) is thermally stable but reacts with CO, affording 3-chloro-1
      proprene and RhCl(SiNP)(CO) (5). Finally, upon reaction of Rh(acac)(SiNP) (4) and
      3-chloro-1-proprene, RhCl(acac)(eta(1)-C(3)H(5))(SiNP) (9a) and [Rh(acac)(eta(3)
      C(3)H(5))(SiNP)]Cl (9b) could be detected at 233 K. At higher temperatures, 9a
      and 9b smoothly decompose, affording the dinuclear derivative [RhCl(SiNP)](2) (2)
      and the CC coupling product 3-allylpentane-2,4-dione.

PMID- 21939190
TI  - Conversion of potassium titanate nanowires into titanium oxynitride nanotubes.
AB  - Tunnel-structured potassium titanate with a K(3)Ti(8)O(17) phase was synthesized
      by direct oxidation of titanium powder mixed with KF(aq) in water vapor at 923 K.
      The reaction conditions were adjusted so that uniform single crystalline
      potassium titanate nanowires with [010] growth direction (length: 5-30 MUm,
      diameter: 80-100 nm) were obtained. Nitridation of the nanowires by NH(3)(g) at
      973-1073 K converted the titanate nanowires into rock-salt structured cubic phase
      single crystalline titanium oxynitride TiN(x)O(y) nanotubes (x = 0.88, y = 0.12,
      length = 1-10 MUm, diameter = 150-250 nm, wall thickness = 30 - 50 nm) and
      nanorods (x = 0.5, y = 0.5, length = 1-5 MUm, diameter = 100-200 nm) with rough
      surfaces and [200] growth direction. The overall conversion of the titanate
      nanowires into the nanotubes and the nanorods can be rationalized by Ostwald
      ripening mechanism. We fabricated an electrode by adhering TiN(x)O(y) nanotubes
      (0.2 mg) on a screen-printed carbon electrode (geometric area: 0.2 cm(2)).
      Electrochemical impedance spectroscopy demonstrated its charge transfer
      resistance to be 20Omega. The electrochemical surface area of the nanotubes on
      the electrode was characterized by cyclic voltammetry to be 0.32 cm(2). This
      property suggests that the TiN(x)O(y) nanostructures can be employed as potential
      electrode materials for electrochemical applications.

PMID- 21939191
TI  - Family of double-cubane Mn4Ln2 (Ln = Gd, Tb, Dy, Ho) and Mn4Y2 complexes: a new
      Mn4Tb2 single-molecule magnet.
AB  - The synthesis and characterization of a family of Mn(2)(III)Mn(2)(II)Ln(III)(2)
      complexes (Ln = Gd (1), Tb (2), Dy (3), and Ho (4)) of formula
      [Mn(4)Ln(2)O(2)(O(2)CBu(t))(6)(edteH(2))(2)(NO(3))(2)] are reported, where
      edteH(4) is N,N,N',N'-tetrakis(2-hydroxyethyl)ethylenediamine. The analogous
      Mn(4)Y(2) (5) complex has also been prepared. They were obtained from reaction of
      Ln(NO(3))(3) or Y(NO(3))(3) with Mn(O(2)CBu(t))(2), edteH(4), and NEt(3) in a
      2:3:1:2 molar ratio. The crystal structures of representative 1 and 2 were
      obtained, and their core consists of a face-fused double-cubane [Mn(4)Ln(2)(MU(4)
      O(2-))(2)(MU(3)-OR)(4)] unit. Such double-cubane units are extremely rare in 3d
      metal chemistry and unprecedented in 3d-4f chemistry. Variable-temperature, solid
      state dc and ac magnetic susceptibility studies on 1-5 were carried out. Fitting
      of dc chi(M)T vs T data for 5 gave J(bb) (Mn(III)...Mn(III)) = -32.6(9) cm(-1),
      J(wb) (Mn(II)...Mn(III)) = +0.5(2) cm(-1), and g = 1.96(1), indicating a |n, 0,
      n> (n = 0-5) 6-fold-degenerate ground state. The data for 1 indicate an S = 12
      ground state, confirmed by fitting of magnetization data, which gave S = 12, D =
      0.00(1) cm(-1), and g = 1.93(1) (D is the axial zero-field splitting parameter).
      This ground state identifies the Mn(II)...Gd(III) interactions to be
      ferromagnetic. The ac susceptibility data independently confirmed the conclusions
      about 1 and 5 and revealed that 2 displays slow relaxation of the magnetization
      vector for the Mn(4)Tb(2) analogue 2. The latter was confirmed as a single
      molecule magnet by observation of hysteresis below 0.9 K in magnetization vs dc
      field scans on a single crystal of 2.MeCN on a micro-SQUID apparatus. The
      hysteresis loops also displayed well-resolved quantum tunneling of magnetization
      steps, only the second 3d-4f SMM to do so.

PMID- 21939192
TI  - Combined experimental and theoretical study on redox-active d8 metal dithione
      dithiolato complexes showing molecular second-order nonlinear optical activity.
AB  - Synthesis, characterization, NLO properties, and theoretical studies of the mixed
      ligand dithiolene complexes of the nickel triad [M(II)(Bz(2)pipdt)(mnt)]
      (Bz(2)pipdt = 1,4-dibenzyl-piperazine-3,2-dithione, mnt = maleonitriledithiolato,
      M(II) = Ni, 1, Pd, 2, Pt, 3) are reported. Molecular structural characterization
      of 1-3 points out that four sulfur atoms are in a slightly distorted square
      planar geometry. While the M-S bond distances are only slightly different,
      comparison of the C-C and C-S bonds in the C(2)S(2)MS(2)C(2) core allows us to
      point out a significant difference between the C-C and the C-S distances in
      Bz(2)pipdt and mnt. These findings suggest assigning a dithiolato character to
      mnt (pull ligand) and a dithione one (push ligand) to Bz(2)pipdt. Cyclic
      voltammetry of 1-3 exhibits two reversible reduction waves and a broad
      irreversible oxidation wave. These complexes are characterized in the visible
      region by a peak of moderately strong intensity, which undergoes negative
      solvatochromism. The molecular quadratic optical nonlinearities were determined
      by the EFISH technique, which provided the following values MUbeta(lambda) (10(
      48) esu) = -1436 (1), -1450 (2), and -1950 (3) converted in MUbeta(0) (10(-48)
      esu) = -463 (1), -684 (2), and -822 (3), showing that these complexes exhibit
      large negative second-order polarizabilities whose values depend on the metal,
      being highest for the Pt compound. DFT and TD-DFT calculations on 1-3 allow us to
      correlate geometries and electronic structures. Moreover, the first molecular
      hyperpolarizabilities have been calculated, and the results obtained support that
      the most appealing candidate as a second-order NLO chromophore is the platinum
      compound. This is due to (i) the most extensive mixture of the
      dithione/metal/dithiolato orbitals, (ii) the influence of the electric field of
      the solvent on the frontier orbitals that maximizes the difference in dipole
      moments between the excited and the ground state, and (iii) the largest
      oscillator strength in the platinum case vs nickel and palladium ones.

PMID- 21939193
TI  - Dimethylplatinum(II) complexes: computational insights into Pt-C bond
      protonolysis.
AB  - A detailed density functional theory (DFT) study of the protonation and
      subsequent methane elimination reactions of dimethylplatinum(II) complexes in
      presence of triflic acid in various solvents has been undertaken to contribute to
      the debate concerning the mechanism of the electrophilic cleavage of the Pt-C
      bond in Pt(II) complexes. Both mechanisms of direct one-step proton attack at the
      Pt-C bond (S(E)2) and stepwise oxidative-addition on the central metal followed
      by reductive elimination (S(E)(ox)) have been explored for a series of
      dimethylplatinum(II) complexes changing the nature of the ancillary ligands and
      the solvent. Theoretical calculations show that the most likely mechanism cannot
      be predicted on the basis of spectator ligands donating properties only. A one
      step protonolysis pathway is characteristic for complexes containing P based
      ligands, whereas for complexes containing N based and, in general, hard poor
      donor ligands a common behavior cannot be indicated. Solvent nucleophilicity can
      influence the rate of the S(E)(ox) rate mechanism, whereas its steric hindrance
      can induce a change of the preferred mechanism. The hypothesis that five
      coordinate methyl hydrido platinum(IV) intermediates might be formed along the
      S(E)(ox) pathway is not supported. Only six-coordinate Pt(IV) hydride complexes
      are calculated to be stable intermediates generated by direct protonation at the
      platinum center. Formation and experimental detection of six-coordinate Pt(IV)
      hydrides, nevertheless, cannot be considered a definite evidence that a S(E)(ox)
      mechanism is operative because such intermediates can be also generated by a
      hydrogen migration to Pt from the carbon atom of the sigma-complex methane
      molecule formed by a S(E)2 attack. For all the examined complexes methane loss
      occurs by an associative mechanism. Both solvent and anion of the acid can assist
      methane displacement. Calculations have been also carried out to probe whether
      the preference for a concerted or a stepwise mechanism should be predicted on the
      basis of two proposed criteria: metal-complex charge distribution as a
      consequence of the Pt-C bond polarization and the nature of the highest occupied
      molecular orbital (HOMO).

PMID- 21939194
TI  - Peptide-bound dinitrosyliron complexes (DNICs) and neutral/reduced-form Roussin's
      red esters (RREs/rRREs): understanding nitrosylation of [Fe-S] clusters leading
      to the formation of DNICs and RREs using a de novo design strategy.
AB  - This manuscript describes the interaction of low-molecular-weight DNICs with
      short peptides designed to explore the stability and structure of DNIC
      peptide/RRE-peptide constructs. Although characterization of protein-bound and
      low-molecular-weight DNICs is possible via EPR, XAS, and NRVS, this study
      demonstrates that the combination of aqueous IR nu(NO) and UV-vis spectra can
      serve as an efficient tool to characterize and discriminate peptide-bound DNICs
      and RREs. The de novo chelate-cysteine-containing peptides KC(A)(n)CK-bound (n =
      1-4) dinitrosyliron complexes KC(A)(n)CK-DNIC (CnA-DNIC) and monodentate-cysteine
      containing peptides KCAAK-/KCAAHK-bound Roussin's red esters (RREs) KCAAK
      RRE/KCAAHK-RRE were synthesized and characterized by aqueous IR, UV-vis, EPR, CD,
      XAS, and ESI-MS. In contrast to the inertness of chelate-cysteine-containing
      peptide-bound DNICs toward KCAAK/KCAAHK, transformation of KCAAK-RRE/KCAAHK-RRE
      into CnA-DNIC triggered by CnA and reversible transformation between CnA-DNIC and
      CnA-RRE via {Fe(NO)(2)}(9)-{Fe(NO)(2)}(10) reduced-form peptide-bound RREs
      demonstrate that the {Fe(NO)(2)}(9) motif displays a preference for chelate
      cysteine-containing peptides over monodentate-cysteine-containing peptides. Also,
      this study may signify that nitrosylation of [Fe-S] proteins generating protein
      bound RREs, reduced protein-bound RREs, or protein-bound DNICs are modulated by
      both the oxidation state of iron and the chelating effect of the bound proteins
      of [Fe-S] clusters.

PMID- 21939195
TI  - Temperature-dependent exchange interaction in molecular magnets Cu(hfac)2L(R)
      studied by EPR: methodology and interpretations.
AB  - Exchange-coupled spin triads nitroxide-copper(II)-nitroxide are the key building
      blocks of molecular magnets Cu(hfac)(2)L(R). These compounds exhibit thermally
      induced structural rearrangements and spin transitions, where the exchange
      interaction between spins of copper(II) ion and nitroxide radicals changes
      typically by 1 order of magnitude. We have shown previously that electron
      paramagnetic resonance (EPR) spectroscopy is sensitive to the observed magnetic
      anomalies and provides information on both inter- and intracluster exchange
      interactions. The value of intracluster exchange interaction is temperature
      dependent (J(T)), that can be accessed by monitoring the effective g-factor of
      the spin triad as a function of temperature (g(eff)(T)). This paper describes
      approaches for studying the g(eff)(T) and J(T) dependences and establishes
      correlations between them. The experimentally obtained g(eff)(T) dependences are
      interpreted using three different models for the mechanism of structural
      rearrangements on the molecular level leading to different meanings of the J(T)
      function. The contributions from these mechanisms and their manifestations in X
      ray, magnetic susceptibility and EPR data are discussed.

PMID- 21939196
TI  - Convenient syntheses of benzo-fluorinated dibenz[b,f]azepines: rearrangements of
      isatins, acridines, and indoles.
AB  - Efficient procedures for the synthesis of benzo-fluorinated dibenz[b,f]azepines
      (iminostilbenes) from fluorinated isatins or indoles using a number of ring
      expansion reactions are described. A range of mono- and difluorinated analogues
      is accessible, and the syntheses can deliver gram quantities of the final
      products, which are precursors of fluoro analogues of the important
      anticonvulsant carbamazepine.

PMID- 21939197
TI  - A highly active nano-palladium catalyst for the preparation of aromatic azos
      under mild conditions.
AB  - A worm-like Pd nanocatalyst has been prepared and used in the preparation of azo
      compounds from nitroaromatics under mild reaction conditions. This highly
      dispersible nano-Pd catalyst shows high activity toward the synthesis of both
      symmetric aromatic azo compounds and a range of asymmetric aromatic azo
      compounds.

PMID- 21939198
TI  - Negative enrichment of target cells by microfluidic affinity chromatography.
AB  - A three-dimensional microfluidic channel was developed for high-purity cell
      separations. This system featured high capture affinity using multiple vertical
      inlets to an affinity surface. In cell separations, positive selection (capture
      of the target cell) is usually employed. Negative enrichment, the capture of
      nontarget cells and elution of target cells, has distinct advantages over
      positive selection. In negative enrichment, target cells are not labeled and are
      not subjected to strenuous elution conditions or dilution. As a result, negative
      enrichment systems are amenable to multistep processes in microfluidic systems.
      In previous work (Li, P.; Tian, Y.; Pappas, D. Anal. Chem.2011, 83, 774-781), we
      reported cell capture enhancement effects at vertical inlets to the affinity
      surface. In this study, we designed a chip that has multiple vertical and
      horizontal channels, forming a three-dimensional separation system. Enrichment of
      target cells showed separation purities of 92-96%, compared with straight-channel
      systems (77% purity). A parallelized chip was also developed for increased sample
      throughput. A two-channel system showed similar separation purity with twice the
      sample flow rate. This microfluidic system, featuring high separation purity and
      ease of fabrication and use is suitable for cell separations when subsequent
      analysis of target cells is required.

PMID- 21939199
TI  - A facile Cu(I)/BINAP-catalyzed asymmetric approach to functionalized
      pyroglutamate derivatives bearing a unique quaternary stereogenic center.
AB  - A direct and facile access to enantioenriched pyroglutamate derivatives bearing a
      unique quaternary stereogenic center has been developed via Cu(I)/BINAP-catalyzed
      tandem Michael addition-elimination of alpha-substituted aldimino esters with
      Morita-Baylis-Hillman (MBH) carbonates followed by a deprotection/lactamization
      protocol, which performs well over a broad scope of substrates and provides
      biologically active pyroglutamate derivatives in good yields and excellent
      enantioselectivities.

PMID- 21939200
TI  - Phenanthrene-fused azo-ene-ynes: synthesis of dibenzo[f,h]cinnoline and
      dibenzo[e,g]isoindazole derivatives.
AB  - The cyclization reactions of a phenanthreno-fused azo-ene-yne compound have been
      studied both experimentally and computationally. Experimental results show that
      this system is prone to dimerization, more so than previously studied naphthalene
      and benzene-based analogues. Calculations reveal that pyrazoles and arene-fused
      pyrazoles strongly stabilize carbenes in the 5-position through "coarctate
      conjugation", suggesting a stationary concentration of the carbenes/carbenoids
      during cyclization that is high enough for dimerization.

PMID- 21939201
TI  - Direct Hiyama cross-coupling of enaminones with triethoxy(aryl)silanes and
      dimethylphenylsilanol.
AB  - 2,3-Dihydropyridin-4(1H)-ones undergo direct C-H functionalization at C5 in the
      palladium(II)-catalyzed Hiyama reaction, using triethoxy(aryl)silanes and
      dimethylphenylsilanol. The reagent CuF(2) has a dual role in the reactions with
      triethoxy(aryl)silanes. It is a source of fluoride to activate the silane in the
      Hiyama reaction and also serves as the reoxidant to convert Pd(0) to Pd(II) in
      the catalytic cycle.

PMID- 21939203
TI  - Ate complexes of secondary boronic esters as chiral organometallic-type
      nucleophiles for asymmetric synthesis.
AB  - The addition of an aryllithium reagent to a secondary boronic ester leads to an
      intermediate boron-ate complex that behaves as a chiral nucleophile, reacting
      with a broad range of electrophiles with inversion of stereochemistry. Depending
      on the electrophile, the C-B bond can be converted into C-I, C-Br, C-Cl, C-N, C
      O, and C-C, all with very high levels of stereocontrol. This discovery now adds a
      new, readily available, configurationally stable, chiral organometallic-type
      reagent to the arsenal of methods for use in asymmetric organic synthesis.

PMID- 21939202
TI  - A study of the alpha-helical intermediate preceding the aggregation of the amino
      terminal fragment of the beta amyloid peptide (Abeta(1-28)).
AB  - The beta amyloid (Abeta) peptide aggregates to form beta-rich structures that are
      known to trigger Alzheimer's disease. Experiments suggest that an alpha-helical
      intermediate precedes the formation of these aggregates. However, a description
      at the molecular level of the alpha-to-beta transition has not been obtained.
      Because it has been proposed that the transition might be initiated in the amino
      terminal region of Abeta, we studied the aggregation of the 28-residue amino
      terminal fragment of Abeta (Abeta(1-28)) using molecular dynamics and a coarse
      grained force field. Simulations starting from extended and helical conformations
      showed that oligomerization is initiated by the formation of intermolecular beta
      sheets between the residues in the N-terminal regions. In simulations starting
      from the alpha-helical conformation, forcing residues 17-21 to remain in the
      initial (helical) conformation prevents aggregation but allows for the formation
      of dimers, indicating that oligomerization, initiated along the nonhelical N
      terminal regions, cannot progress without the alpha-to-beta transition
      propagating along the chains.

PMID- 21939204
TI  - Novel synthesis of stable polypyrrole nanospheres using ozone.
AB  - In this study, a novel and exceedingly simple method for the aqueous synthesis of
      stable, unagglomerated polypyrrole nanospheres was investigated. The method is
      template- and surfactant-free and uses only pyrrole monomer, water, and ozone.
      When the monomer concentration, exposure time to ozone, and temperature were
      varied, it was determined that the temperature was the critical factor
      controlling the particle size through particle size measurements via dynamic
      light scattering and transmission electron microscopy (TEM). From the particle
      size measurements, a particle size distribution with a number-weighted mean
      diameter of 73 nm and a standard deviation of 18 nm was achieved. The particles
      were also investigated using zeta-potential measurements, ultraviolet-visible (UV
      vis) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, and
      thermogravimetric analysis in an effort to determine the identity of the
      nanoparticles as well as the mechanism by which the nanoparticles are formed and
      stabilized.

PMID- 21939205
TI  - Ultrasmall functional ferromagnetic nanostructures grown by focused electron-beam
      induced deposition.
AB  - We have successfully grown ultrasmall cobalt nanostructures (lateral size below
      30 nm) by optimization of the growth conditions using focused electron-beam
      induced deposition techniques. This direct-write nanolithography technique is
      thus shown to produce unprecedented resolution in the growth of magnetic
      nanostructures. The challenging magnetic characterization of such small
      structures is here carried out by means of electron holography techniques. Apart
      from growing ultranarrow nanowires, very small Hall sensors have been created and
      their large response has been unveiled.

PMID- 21939206
TI  - Shaken, not stirred: collapsing a peptoid monolayer to produce free-floating,
      stable nanosheets.
AB  - Two-dimensional nanomaterials play a critical role in biology (e.g., lipid
      bilayers) and electronics (e.g., graphene) but are difficult to directly
      synthesize with a high level of precision. Peptoid nanosheet bilayers are a
      versatile synthetic platform for constructing multifunctional, precisely ordered
      two-dimensional nanostructures. Here we show that nanosheet formation occurs
      through an unusual monolayer intermediate at the air-water interface. Lateral
      compression of a self-assembled peptoid monolayer beyond a critical collapse
      pressure results in the irreversible production of nanosheets. An unusual
      thermodynamic cycle is employed on a preparative scale, where mechanical energy
      is used to buckle an intermediate monolayer into a more stable nanosheet.
      Detailed physical studies of the monolayer-compression mechanism revealed a
      simple preparative technique to produce nanosheets in 95% overall yield by
      cyclical monolayer compressions in a rotating closed vial. Compression of
      monolayers into stable, free-floating products may be a general and preparative
      approach to access 2D nanomaterials.

PMID- 21939207
TI  - Electrophilicities of symmetrically substituted 1,3-diarylallyl cations.
AB  - Kinetics of the reactions of nine symmetrically substituted 1,3-diarylallyl
      cations with different nucleophiles were studied photometrically in
      dichloromethane, acetonitrile, and DMSO solutions. The second-order rate
      constants k(2) were found to follow the correlation log k(2) = s(N)(N + E). The
      electrophilicity parameters E of the title cations were derived, using the known
      values of s(N) and N of the nucleophilic reaction partners, and compared with the
      electrophilicities of analogously substituted benzhydrylium ions. Good linear
      correlations were found between the electrophilicities E and the quantum
      chemically calculated gas-phase methyl anion affinities of the allyl cations and
      the sigma(+) constants of the substituents X.

PMID- 21939208
TI  - Optimization of the bulk heterojunction composition for enhanced photovoltaic
      properties: correlation between the molecular weight of the semiconducting
      polymer and device performance.
AB  - Herein we propose an approach toward the optimization of the photovoltaic
      performance of bulk heterojunctions by tuning the composition of the active layer
      with respect to the molecular weight of the semiconducting polymer. We used a
      poly(3-hexylthiophene):[6,6]-phenyl-C61-butyric acid methyl ester (P3HT:PCBM)
      blend as a typical system and varied the molecular weight of the P3HT
      semiconducting polymer in order to determine its influence on the bulk
      heterojunction morphology as well as on the optoelectronic characteristics of the
      device. We have systematically mapped out the phase diagram for different
      molecular weight P3HTs blended with PCBM and observed the presence of a eutectic
      composition, which shifts to higher content of P3HT for lower molecular weight
      P3HTs. This shift inherent to the P3HT molecular weight is also apparent in the
      photovoltaic performance as the eutectic composition corresponds to the best of
      the photovoltaic properties. The P3HT molecular weight dependence of the eutectic
      composition is due to the molecular weight dependence of the P3HT crystallization
      behavior, which leads to dramatic morphological changes of the bulk
      heterojunction.

PMID- 21939209
TI  - Direct fabrication of all-cellulose nanocomposite from cellulose microfibers
      using ionic liquid-based nanowelding.
AB  - All-cellulose nanocomposite was directly fabricated using nanowelding of
      cellulose microfibers as a starting material, in 1-butyl-3-methylimidazolium
      chloride (BMIMCl) as a solvent, for the first time. The average diameter of the
      reinforcing component (undissolved nanofibrils) in the nanocomposite made
      directly from cellulose microfibers (NC-microfiber) was 53 +/- 16 nm. Owing to
      its high mechanical properties (tensile strength of 208 MPa and Young's modulus
      of 20 GPa), high transparency (76% at a wavelength of 800 nm), and complete
      barrier to air and biodegradability, the NC-microfiber is regarded as a high
      multiperformance material. The NC-microfiber made directly from cellulose
      microfibers showed similar macro-, micro-, and nanostructures and the same
      properties as those made from solvent-based welding of ground cellulose
      nanofibers (NC-nanofiber). Omitting the step of cellulose nanofiber production
      makes the direct production of all-cellulose nanocomposite from cellulose
      microfibers easier, shorter, and cheaper than using cellulose nanofibers as
      starting material. The direct nanowelding of macro/micrometer-sized materials is
      theorized to be a fundamental approach for making nanocomposites.

PMID- 21939210
TI  - In vivo fluorescence imaging of bone-resorbing osteoclasts.
AB  - Osteoclasts are giant polykaryons responsible for bone resorption. Because an
      enhancement or loss of osteoclast function leads to bone diseases such as
      osteoporosis and osteopetrosis, real-time imaging of osteoclast activity in vivo
      can be of great help for the evaluation of drugs. Herein, pH-activatable chemical
      probes BAp-M and BAp-E have been developed for the detection of bone-resorbing
      osteoclasts in vivo. Their acid dissociation constants (pK(a)) were determined as
      4.5 and 6.2 by fluorometry in various pH solutions. These pK(a) values should be
      appropriate to perform selective imaging of bone-resorbing osteoclasts, because
      synthesized probes cannot fluoresce intrinsically at physiological pH and the pH
      in the resorption pit is lowered to about 4.5. Furthermore, BAp-M and BAp-E have
      a bisphosphonate moiety that enabled the probes to localize on bone tissues. The
      hydroxyapatite (HA) binding assay in vitro was, therefore, performed to confirm
      the tight binding of the probes to the bone tissues. Our probes showed intense
      fluorescence at low pH values but no fluorescence signal under physiological pH
      conditions on HA. Finally, we applied the probes to in vivo imaging of
      osteoclasts by using intravital two-photon microscopy. As expected, the
      fluorescence signals of the probes were locally observed between the osteoclasts
      and bone tissues, that is, in resorption pits. These results indicate that our pH
      activatable probes will prove to be a powerful tool for the selective detection
      of bone-resorbing osteoclasts in vivo, because this is the first instance where
      in vivo imaging has been conducted in a low-pH region created by bone-resorbing
      osteoclasts.

PMID- 21939211
TI  - Mechanistic studies of the lithium enolate of 4-fluoroacetophenone: rapid
      injection NMR study of enolate formation, dynamics, and aldol reactivity.
AB  - Lithium enolates are widely used nucleophiles with a complicated and only
      partially understood solution chemistry. Deprotonation of 4-fluoroacetophenone in
      THF with lithium diisopropylamide occurs through direct reaction of the amide
      dimer to yield a mixed enolate-amide dimer (3), then an enolate homodimer (1
      Li)(2), and finally an enolate tetramer (1-Li)(4), the equilibrium structure.
      Aldol reactions of both the metastable dimer and the stable tetramer of the
      enolate were investigated. Each reacted directly with the aldehyde to give a
      mixed enolate-aldolate aggregate, with the dimer only about 20 times as reactive
      as the tetramer at -120  degrees C.

PMID- 21939212
TI  - Analysis of electronic states and energy level structure of uranyl in compounds.
AB  - An effective operator Hamiltonian has been developed for evaluating the excited
      states of uranyl ion in compounds. Including free-ion and crystal-field
      interactions, the parametrized Hamiltonian is able to reproduce the energy level
      structure in good agreement with experimental measurements on uranyl in chloride
      compounds and nitride complexes. It is shown that the low-lying excited states
      belong to a nonbonding sigmaf configuration (therefore, one Slater integral of
      G(3) is sufficient to account for the Coulomb electron exchange interaction) and
      that the spin-orbit coupling surpasses the electrostatic interactions in energy
      level splitting. In comparison with previously reported ab initio calculations,
      the present studies find that the Coulomb interactions in uranyl were excessively
      evaluated in the first-principle calculations.

PMID- 21939213
TI  - Scaling of excitons in graphene nanoribbons with armchair shaped edges.
AB  - The scaling behavior of band gaps and fundamental quantities of exciton, i.e.,
      reduced mass, size, and binding strength, in three families of quasi one
      dimensional graphene nanoribbons with hydrogen passivated armchair shaped edge
      (AGNRs) are comprehensively investigated by density functional theory with quasi
      particle corrections and many body, i.e., electron-hole, interactions. Compared
      with single-walled carbon nanotubes (SWCNTs) where the scaling character features
      a single exponent, each family of AGNRs has its own single exponent, due to its
      intrinsic zero curvature, which also accounts for the absent "family spreading"
      of optical transition energies in the smaller width region in the Kataura plots
      of AGNRs as compared to those of SWCNTs. Moreover, the scaling relation between
      exciton binding strength and the geometric parameter is established.

PMID- 21939214
TI  - High-reactivity matrices increase the sensitivity of matrix enhanced secondary
      ion mass spectrometry.
AB  - Secondary ion mass spectrometry (SIMS) is a desorption/ionization method in which
      ions are generated by the impact of a primary ion beam on a sample. Classic
      matrix assisted laser desorption and ionization (MALDI) matrices can be used to
      increase secondary ion yields and decrease fragmentation in a SIMS experiment,
      which is referred to as matrix enhanced SIMS (ME-SIMS). Contrary to MALDI, the
      choice of matrices for ME-SIMS is not constrained by their photon absorption
      characteristics. This implies that matrix compounds that exhibit an insufficient
      photon absorption coefficient have the potential of working well with ME-SIMS.
      Here, we evaluate a set of novel derivatives of the classical MALDI matrices
      alpha-cyano-4-hydroxycinnamic acid (CHCA) and 2,5-dihydroxybenzoic acid (DHB) for
      usability in ME-SIMS. This evaluation was carried out using peptide mixtures of
      different complexity and demonstrates significant improvements in signal
      intensity for several compounds with insufficient UV absorption at the standard
      MALDI laser wavelengths. Our study confirms that the gas-phase proton affinity of
      a matrix compound is a key physicochemical characteristic that determines its
      performance in a ME-SIMS experiment. As a result, these novel matrices improve
      the performance of matrix enhanced secondary ion mass spectrometry experiments on
      complex peptide mixtures.

PMID- 21939215
TI  - Variable volume loading method: a convenient and rapid method for measuring the
      initial emittable concentration and partition coefficient of formaldehyde and
      other aldehydes in building materials.
AB  - The initial emittable formaldehyde and VOC concentration in building materials
      (C(0)) is a key parameter for characterizing and classifying these materials.
      Various methods have been developed to measure this parameter, but these
      generally require a long test time. In this paper we develop a convenient and
      rapid method, the variable volume loading (VVL) method, to simultaneously measure
      C(0) and the material/air partition coefficient (K). This method has the
      following features: (a) it requires a relatively short experimental time (less
      than 24 h for the cases studied); and (b) is convenient for routine measurement.
      Using this method, we determined C(0) and K of formaldehyde, propanal and hexanal
      in one kind of medium density fiberboard, and repeated experiments were performed
      to reduce measurement error. In addition, an extended-C-history method is
      proposed to determine the diffusion coefficient and the convective mass transfer
      coefficient. The VVL method is validated by comparing model predicted results
      based on the determined parameters with experimental data. The determined C(0) of
      formaldehyde obtained via this method is less than 10% of the total concentration
      using the perforator method recommended by the Chinese National Standard,
      suggesting that the total concentration may not be appropriate to predict
      emission characteristics, nor for material classification.

PMID- 21939216
TI  - Impact assessment of ammonia emissions on inorganic aerosols in East China using
      response surface modeling technique.
AB  - Ammonia (NH(3)) is one important precursor of inorganic fine particles; however,
      knowledge of the impacts of NH(3) emissions on aerosol formation in China is very
      limited. In this study, we have developed China's NH(3) emission inventory for
      2005 and applied the Response Surface Modeling (RSM) technique upon a widely used
      regional air quality model, the Community Multi-Scale Air Quality Model (CMAQ).
      The purpose was to analyze the impacts of NH(3) emissions on fine particles for
      January, April, July, and October over east China, especially those most
      developed regions including the North China Plain (NCP), Yangtze River delta
      (YRD), and the Pearl River delta (PRD). The results indicate that NH(3) emissions
      contribute to 8-11% of PM(2.5) concentrations in these three regions, comparable
      with the contributions of SO(2) (9-11%) and NO(x) (5-11%) emissions. However,
      NH(3), SO(2), and NO(x) emissions present significant nonlinear impacts; the
      PM(2.5) responses to their emissions increase when more control efforts are taken
      mainly because of the transition between NH(3)-rich and NH(3)-poor conditions.
      Nitrate aerosol (NO(3)(-)) concentration is more sensitive to NO(x) emissions in
      NCP and YRD because of the abundant NH(3) emissions in the two regions, but it is
      equally or even more sensitive to NH(3) emissions in the PRD. In high NO(3)(-)
      pollution areas such as NCP and YRD, NH(3) is sufficiently abundant to neutralize
      extra nitric acid produced by an additional 25% of NO(x) emissions. The 90%
      increase of NH(3) emissions during 1990-2005 resulted in about 50-60% increases
      of NO(3)(-) and SO(4)(2-) aerosol concentrations. If no control measures are
      taken for NH(3) emissions, NO(3)(-) will be further enhanced in the future.
      Control of NH(3) emissions in winter, spring, and fall will benefit PM(2.5)
      reduction for most regions. However, to improve regional air quality and avoid
      exacerbating the acidity of aerosols, a more effective pathway is to adopt a
      multipollutant strategy to control NH(3) emissions in parallel with current SO(2)
      and NO(x) controls in China.

PMID- 21939217
TI  - Ganodone, a bioactive benzofuran from the fruiting bodies of Ganoderma tsugae.
AB  - Extracts of Ganoderma tsugae, also known as the Hemlock varnish shelf mushroom,
      and related Reishi mushrooms are well documented in traditional Chinese medicine.
      Several Ganoderma sp. are currently cultivated for use in coffee, teas, and
      dietary supplements. We now report on the isolation and characterization of an
      unprecedented benzofuran, ganodone (1), from the fruiting bodies of mature growth
      G. tsugae. This discovery provides a key next step in evaluating the active
      components in their associated herbal supplements.

PMID- 21939218
TI  - Antifouling properties of simple indole and purine alkaloids from the
      Mediterranean gorgonian Paramuricea clavata.
AB  - Chemical investigation of the Mediterranean gorgonian Paramuricea clavata
      resulted in the isolation of two new alkaloids, 2-bromo-N-methyltryptamine (1)
      and 3-bromo-N-methyltyramine (2), together with nine known compounds (3-10 and
      linderazulene). The bromoindole derivative 3 is reported herein for the first
      time from a natural source. The chemical structures of these compounds were
      assigned by spectroscopic analyses and comparison with literature values. The
      antifouling activity and toxicity of compounds 1-10 were assessed using three
      marine biofilm bacteria and the Microtox assay. In contrast to commercial
      antifoulants, bufotenine (5) and 1,3,7-trimethylisoguanine (10) showed
      significant antiadhesion activity against one bacterial strain while being
      nontoxic.

PMID- 21939219
TI  - Benzofurans from Styrax agrestis as acetylcholinesterase inhibitors: structure
      activity relationships and molecular modeling studies.
AB  - An extract of Styrax agrestis fruits, collected in Vietnam, significantly
      inhibited acetylcholinesterase (AChE) in vitro. Bioassay-guided fractionation
      revealed three new egonol-type benzofurans: egonol-9(Z),12(Z) linoleate (1), 7
      demethoxyegonol-9(Z),12(Z) linoleate (2), and 7-demethoxyegonol oleate (4). Ten
      known egonol-type benzofurans were also isolated (3, 5, 6-13). In order to better
      understand structure-activity relationships in this series, egonol derivatives 14
      19 were prepared by chemical modifications and evaluated for their inhibition of
      AChE, butyrylcholinesterase (BChE), and AChE-induced Abeta aggregation. Compounds
      1-4 were the most potent inhibitors of the series, which exhibited inhibitory
      activity against AChE (IC50 1.4-3.1 MUM) and, for 1, Abeta aggregation (77.6%).
      Molecular docking studies were also performed to investigate interaction of these
      compounds with the active site of AChE.

PMID- 21939220
TI  - Hearing what you cannot see and visualizing what you hear: interpreting quartz
      crystal microbalance data from solvated interfaces.
AB  - Over the last 2 decades, the quartz crystal microbalance (QCM or QCM-D) has
      emerged as a versatile tool for investigating soft and solvated interfaces
      between solid surfaces and bulk liquids because it can provide a wealth of
      information about key structural and functional parameters of these interfaces.
      In this Feature, we offer QCM users a set of guidelines for interpretation and
      quantitative analysis of QCM data based on a synthesis of well-established
      concepts rooted in rheological research of the last century and of new results
      obtained in the last several years.

PMID- 21939221
TI  - Kinetics of photochromic conversion at the solid state: quantum yield of
      dithienylethene-based films.
AB  - Quantum yield is one of the most important properties of photochromic systems.
      Unfortunately, a lack of data at the solid state exists, because measurements are
      intrinsically not straightforward. A kinetic model describing the conversion of
      the photoactive species is reported and both analytic and numeric solutions are
      provided according to relevant cases. The model is then applied to measure the
      quantum yield of dithienylethene-based polymers; the ring-opening quantum yield
      is measured for different laser beam profiles (i.e., Gaussian and uniform) and at
      different wavelengths, showing an increased value with increasing photon energy.

PMID- 21939222
TI  - Elaboration of nanostructured biointerfaces with tunable degree of coverage by
      protein nanotubes using electrophoretic deposition.
AB  - This study shows that electrophoretic deposition (EPD) is a fast and efficient
      technique for producing protein nanotube-based biointerfaces. Well-shaped
      collagen-based nanotubes of controlled dimensions are synthesized by a template
      method combined with the layer-by-layer (LbL) assembly technique. Separation of
      nanotubes from the template material and collection of nanotubes on ITO glass
      carried out by EPD leads to a fairly homogeneous distribution of protein
      nanotubes at the support surface. Biointerfaces with different and tunable
      densities of protein nanotubes are obtained by changing either the applied
      voltage, solution concentration of nanotubes, or deposition time. Moreover, it is
      proved that the collected nanotubes are template-free and keep their
      biofunctional outermost layer after EPD. A preliminary study of the behavior of
      preosteoblasts cells with the elaborated biointerfaces indicates a specific
      interaction of cells with the nanotubes through filopodia. This contribution
      paves the way to the easy preparation of a large variety of useful nanostructured
      collagen and other protein-based interfaces for controlling cell-surface
      interactions in diverse biomaterials applications.

PMID- 21939223
TI  - Charge density and pH effects on polycation adsorption on poly-Si, SiO2, and
      Si3N4 films and impact on removal during chemical mechanical polishing.
AB  - The pH-dependent interactions of five aqueous abrasive-free polycationic
      solutions, all at a concentration of 250 ppm, with poly-Si, SiO(2), and Si(3)N(4)
      films and IC1000 polishing pads used in chemical mechanical polishing have been
      investigated and compared with the interaction of poly(diallyldimethyl ammonium
      chloride) (PDADMAC) that was investigated recently. Three of the polycationic
      solutions, poly(dimethylamine-co-epichlorohydrin-co-ethylenediamine),
      poly(allylamine), and poly(ethylene imine) (PEI) enhance poly-Si removal rates
      (RRs) to the range of about 500 to 600 nm/min at pH 10. In contrast,
      poly(acrylamide) (PAA) suppressed poly-Si RRs to about 50 nm/min, whereas with a
      copolymer of PAA and PDADMAC, the RRs were lower than those obtained with PDADMAC
      but higher than those obtained with PAA. For all the polycationic solutions, the
      RRs of both SiO(2), and Si(3)N(4) films were ~0 nm/min. These solutions offer a
      low-defect option for the processing of emerging FinFET devices. The variation in
      the RR magnitude and dependence on pH among the different polycations is related
      to the relative charge density of the polycations as well as the films being
      polished, consistent with zeta potential data. Based on the zeta potential data
      and earlier published reports, it is suggested that the strong polycation
      mediated bridging interactions between the polarized and weakened Si-Si bonds of
      the poly-Si surface and the polyurethane IC 1000 pad are responsible for the high
      poly-Si RRs.

PMID- 21939224
TI  - Broad band focusing and demultiplexing of in-plane propagating surface plasmons.
AB  - On the basis of a novel phase modulation method by in-plane diffraction
      processes, a well-designed nanoarray on metal surface is proposed to realize a
      broad band focusing (bandwidth ~100 nm) and a demultiplexing element (resolution
      ~12 nm) of surface plasmon polariton (SPP) waves. Moreover, sublattice arrays are
      developed to achieve an improved demultiplexer and confocal SPP beams. The
      proposed scheme with implemented functionalities is designed totally in planar
      dimension, which is free of the SPP coupling process and indicates more practical
      application in photonic integrations.

PMID- 21939225
TI  - Screening novel biomarkers for metabolic syndrome by profiling human plasma N
      glycans in Chinese Han and Croatian populations.
AB  - N-glycans play an essential role in biological process and are associated with
      age, gender, and body mass parameters in Caucasian populations, whereas no study
      has been reported in Chinese populations. To investigate the correlation between
      N-glycan structures and metabolic syndrome (MetS) components, we conducted a
      population-based study in 212 Chinese Han individuals. The replication study was
      performed on 520 unrelated individuals from a Croatian island Korcula. The most
      prominent observation was the consistent positive correlations between different
      forms of triantennary glycans and negative correlations between glycans
      containing core-fucose with MetS components including BMI, SBP, DBP, and fasting
      plasma glucose (FPG) simultaneously. Significant differences in a number of N
      glycan traits were also detected between normal and abnormal groups of BMI, BP,
      and FPG, respectively. In the multivariate analysis, the level of monosialylated
      glycans (structure loadings = -0.776) was the most correlated with the MetS
      related risk factors, especially with SBP (structure loadings = 0.907). Results
      presented here are showing that variations in the composition of the N-glycome in
      human plasma could represent the alternations of human metabolism and could be
      potential biomarkers of MetS.

PMID- 21939226
TI  - Environmental impact of pyrolysis of mixed WEEE plastics part 1: Experimental
      pyrolysis data.
AB  - Growth in waste electrical and electronic equipment (WEEE) is posing increasing
      problems of waste management, partly resulting from its plastic content. WEEE
      plastics include a range of polymers, some of which can be sorted and extracted
      for recycling. However a nonrecyclable fraction remains containing a mixture of
      polymers contaminated with other materials, and pyrolysis is a potential means of
      recovering the energy content of this. In preparation for a life cycle assessment
      of this option, described in part 2 of this paper set, data were collected from
      trials using experimental pyrolysis equipment representative of a continuous
      commercial process operated at 800  degrees C. The feedstock contained
      acrylonitrile-butadiene-styrene and high impact polystyrene with high levels of
      additives, and dense polymers including polyvinylchloride, polycarbonate,
      polyphenylene oxide, and polymethyl methacrylate. On average 39% was converted to
      gases, 36% to oils, and 25% remained as residue. About 35% of the gas was methane
      and 42% carbon monoxide, plus other hydrocarbons, oxygen and carbon dioxide. The
      oils were almost all aromatic, forming a similar mixture to fuel oil. The residue
      was mainly carbon with inorganic compounds from the plastic additives and most of
      the chlorine from the feedstock. The results showed that the process produced
      around 70% of the original plastic weight as potential fuel.

PMID- 21939228
TI  - Sn@CNT nanostructures rooted in graphene with high and fast Li-storage
      capacities.
AB  - Development of materials with carefully crafted nanostructures has been an
      important strategy for the next-generation lithium-ion batteries to achieve
      higher capacity, longer cycle life, and better rate capability. Graphene-based
      and Sn-based anode materials are promising anodes with higher capacities than
      graphite; however, most of them exhibit fast capacity fading at prolonged cycling
      and poor rate capability. This paper reports a hierarchical Sn@CNT nanostructure
      rooted in graphene, which exhibits larger than theoretical reversible capacities
      of 1160-982 mAh/g in 100 cycles at 100 mA/g and excellent rate capability (828
      mAh/g at 1000 mA/g and 594 mAh/g at 5000 mA/g). The excellent electrochemical
      performances compared to graphene/Sn-based anodes have been attributed to the
      efficient prevention of graphene agglomeration by Sn@CNT decoration and the
      increased electrochemical activities of Sn by CNT shell protection and GNS
      support.

PMID- 21939227
TI  - Determining the effects of antioxidants on oxidative stress induced carbonylation
      of proteins.
AB  - There is potential that the pathological effects of oxidative stress (OS)
      associated diseases such as diabetes could be ameliorated with antioxidants, but
      this will require a clearer understanding of the pathway(s) by which proteins are
      damaged by OS. This study reports the development and use of methods that assess
      the efficacy of dietary antioxidant supplementation at a mechanistic level. Data
      reported here evaluate the impact of green tea supplementation on oxidative
      stress induced post-translational modifications (OSi-PTMs) in plasma proteins of
      Zucker diabetic fatty (ZDF) rats. The mechanism of antioxidant protection was
      examined through both the type and amount of OSi-PTMs using mass spectrometry
      based identification and quantification. Carbonylated proteins in freshly drawn
      blood samples were derivatized with biotin hydrazide. Proteins thus biotinylated
      were selected from plasma samples of green tea fed diabetic rats and control
      animals by avidin affinity chromatography, further fractionated by reversed phase
      chromatography (RPC); fractions from the RPC column were tryptic digested, and
      the tryptic digest was fractionated by RPC before being identified by tandem mass
      spectrometry (MS/MS). Relative quantification of peptides bearing carbonylation
      sites was achieved for the first time by RPC-MS/MS using selective reaction
      monitoring (SRM). Seventeen carbonylated peptides were detected and quantified in
      both control and treated plasma. The relative concentration of eight was
      dramatically different between control and green tea treated animals. Seven of
      the OSi-PTM bearing peptides had dropped dramatically in concentration with
      treatment while one increased, indicating differential regulation of
      carbonylation by antioxidants. Green tea antioxidants were found to reduce
      carbonylation of proteins by lipid peroxidation end products most, followed by
      advanced glycation end products to a slightly lower extent. Direct oxidation of
      proteins by reactive oxygen species (ROS) was protected the least by green tea.

PMID- 21939229
TI  - Free charges produced by carrier multiplication in strongly coupled PbSe quantum
      dot films.
AB  - We show that in films of strongly coupled PbSe quantum dots multiple electron
      hole pairs can be efficiently produced by absorption of a single photon (carrier
      multiplication). Moreover, in these films carrier multiplication leads to the
      generation of free, highly mobile charge carriers rather than excitons. Using the
      time-resolved microwave conductivity technique, we observed the production of
      more than three electron-hole pairs upon absorption of a single highly energetic
      photon (5.7E(g)). Free charge carriers produced via carrier multiplication are
      readily available for use in optoelectronic devices even without employing any
      complex donor/acceptor architecture or electric fields.

PMID- 21939230
TI  - Correlation of CdS nanocrystal formation with elemental sulfur activation and its
      implication in synthetic development.
AB  - Formation of CdS nanocrystals in the classic approach (with octadecene (ODE) as
      the solvent and elemental sulfur and cadmium carboxylate as the precursors) was
      found to be kinetically dependent on reduction of elemental sulfur by ODE, which
      possessed a critical temperature (~180  degrees C). After elemental sulfur was
      activated by ODE, the formation reaction of CdS followed closely. 2
      tetradecylthiophene from the activation of S by ODE and fatty acids from the
      formation reaction of CdS were found to be the only soluble side products. The
      overall reaction stoichiometry further suggested that oxidation of each ODE
      molecule generated two molecules of H(2)S, which in turn reacted with two
      molecules of cadmium carboxylate molecules to yield two CdS molecular units and
      four molecules of fatty acids. In comparison to alkanes, octadecene was found to
      be substantially more active as a reductant for elemental sulfur. To the best of
      our knowledge, this is the first example of quantitative correlation between
      chemical reactions and formation of high-quality nanocrystals under synthetic
      conditions. To demonstrate the importance of such discovery, we designed two
      independent and simplified synthetic approaches for synthesis of CdS
      nanocrystals. One approach with its reaction temperature at the critical
      temperature of S activation (180  degrees C) used the same reactant composition
      as the classic approach but without any hot injection. The other approach
      performed at an ordinary laboratory temperature (<=100  degrees C) and in a
      common organic solvent (toluene) was achieved by addition of fatty amine as
      activation reagent of elemental sulfur.

PMID- 21939231
TI  - Environmental impact of pyrolysis of mixed WEEE plastics part 2: Life cycle
      assessment.
AB  - Waste electrical and electronic equipment (WEEE) contains up to 25% plastics.
      Extraction of higher quality fractions for recycling leaves a mix of plastic
      types contaminated with other materials, requiring the least environmentally
      harmful disposal route. Data from trials of pyrolysis, described in part 1 of
      this paper set, were used in a life cycle assessment of the treatment of WEEE
      plastics. Various levels of recycling of the sorted fraction were considered, and
      pyrolysis was compared with incineration (with energy recovery) and landfill for
      disposal of the remainder. Increased recycling gave reduced environmental impact
      in almost all categories considered, although inefficient recycling decreased
      that benefit. Significant differences between pyrolysis, incineration and
      landfill were seen in climate change impacts, carbon sent to landfill, resources
      saved, and radiation. There was no overall "best" option. Landfill had the least
      short-term impact on climate change so could be a temporary means of sequestering
      carbon. Incineration left almost no carbon to landfill, but produced the most
      greenhouse gases. Pyrolysis or incineration saved most resources, with the
      balance depending on the source of electricity replaced by incineration.
      Pyrolysis emerged as a strong compromise candidate since the gases and oils
      produced could be used as fuels and so provided significant resource saving
      without high impact on climate change or landfill space.

PMID- 21939232
TI  - Hydrothermally synthesized titanate nanostructures: impact of heat treatment on
      particle characteristics and photocatalytic properties.
AB  - The role titanate particle structure plays in governing its characteristics upon
      calcining and their ensuing influence on photocatalytic performance was
      investigated. Titanate nanotubes and nanoribbons were prepared by hydrothermal
      treatment of Aeroxide P25 and then calcined at temperatures in the range 200 -
      800  degrees C. Heat treatment directly transformed the nanotubes to anatase
      while nanoribbon transformation to anatase occurred via a TiO(2)(B) intermediate
      phase. The nanoribbon structure also provided an increased resistance to
      sintering, allowing for retention of the original {010} facet of the titanate
      nanosheets up to 800  degrees C. The changing material properties with calcining
      were found to influence the capacity of the particles to photodegrade oxalic acid
      and methanol. The nanotubes provided an optimum photoactivity following
      calcination at 500  degrees C with this point representing a transition between
      the relative dominance of crystal phase and surface area on performance. The
      comparatively smaller initial surface area of the nanoribbons consigned this
      characteristic to a secondary role in influencing photoactivity with the changes
      to crystal phase dominating the continually improving performance with
      calcination up to 800  degrees C. The structural stability imparted by the
      nanoribbon architecture during calcination, in particular its retention of the
      {010} facet at temperatures >700  degrees C, advanced its photocatalytic
      performance compared with the nanotubes. This was especially the case for
      methanol photooxidation whose primary degradation mechanism relies on hydroxyl
      radical attack and was facilitated by the {010} facet. The effect was not as
      pronounced for oxalic acid due to its higher adsorption on TiO(2) and therefore
      greater susceptibility to oxidation by photogenerated holes. This study
      demonstrates that, apart from modulating sintering effects and changes to crystal
      phase, the titanate nanostructure influences particle crystallography which can
      be beneficial for photocatalytic performance.

PMID- 21939234
TI  - CO2 saturation, distribution and seismic response in two-dimensional permeability
      model.
AB  - Carbon dioxide capture and storage (CCS) has been actively researched as a
      strategy to mitigate CO(2) emissions into the atmosphere. The three components in
      CCS are monitoring, verification, and accounting (MVA). Seismic monitoring
      technologies can meet the requirements of MVA, but they require a quantitative
      relationships between multiphase saturation distributions and wave propagation
      elastic properties. One of the main obstacles for quantitative MVA activities
      arises from the nature of the saturation distribution, typically classified
      anywhere from homogeneous to patchy. The emerging saturation distribution, in
      turn, regulates the relationship between compressional velocity and saturation.
      In this work, we carry out multiphase flow simulations in a 2-D aquifer model
      with a log-normal absolute permeability distribution and a capillary pressure
      function parametrized by permeability. The heterogeneity level is tuned by
      assigning the value of the Dykstra-Parson (DP) coefficient, which sets the
      variance of the log-normal horizontal permeability distribution in the entire
      domain. Vertical permeability is a 10th of the horizontal value in each gridcell.
      We show that despite apparent differences in saturation distribution among
      different realizations, CO(2) trapping and the V(p)-S(w) Rock Physics
      relationship are mostly functions of the DP coefficient. When the results are
      compared with the well accepted limits, Gassmann-Wood (homogeneous) (A Text Book
      of Sound; G. Bell and Suns LTD: London, 1941) and Gassmann-Hill (patchy) models,
      the V(p)-S(w) relationship never reaches the upper bound, that is, patchy model
      curve, even at the highest heterogeneity level in the model.

PMID- 21939233
TI  - Mechanism for activation of triosephosphate isomerase by phosphite dianion: the
      role of a ligand-driven conformational change.
AB  - The L232A mutation in triosephosphate isomerase (TIM) from  Trypanosoma brucei
      brucei  results in a small 6-fold decrease in k(cat)/K(m) for the reversible
      enzyme-catalyzed isomerization of glyceraldehyde 3-phosphate to give
      dihydroxyacetone phosphate. In contrast, this mutation leads to a 17-fold
      increase in the second-order rate constant for the TIM-catalyzed proton transfer
      reaction of the truncated substrate piece [1-(13)C]glycolaldehyde ([1-(13)C]-GA)
      in D(2)O, a 25-fold increase in the third-order rate constant for the reaction of
      the substrate pieces GA and phosphite dianion (HPO(3)(2-)), and a 16-fold
      decrease in K(d) for binding of HPO(3)(2-) to the free enzyme. Most
      significantly, the mutation also results in an 11-fold decrease in the extent of
      activation of the enzyme toward turnover of GA by bound HPO(3)(2-). The data
      provide striking evidence that the L232A mutation leads to a ca. 1.7 kcal/mol
      stabilization of a catalytically active loop-closed form of TIM (E(c)) relative
      to an inactive open form (E(o)). We propose that this is due to the relief, in
      L232A mutant TIM, of unfavorable steric interactions between the bulky
      hydrophobic side chain of Leu-232 and the basic carboxylate side chain of Glu
      167, the catalytic base, which destabilize E(c) relative to E(o).

PMID- 21939235
TI  - Kinetic analysis of demetalation of synthetic zinc cyclic tetrapyrroles
      possessing an acetyl group at the 3-position: effects of tetrapyrrole structures
      and peripheral substitution.
AB  - Demetalation of three synthetic zinc cyclic tetrapyrroles that possess identical
      peripheral substituents, zinc methyl bacteriopyropheophorbide a (zinc
      bacteriochlorin 1), zinc methyl 3-devinyl-3-acetyl-pyropheophorbide a (zinc
      chlorin 2), and zinc methyl 3-devinyl-3-acetyl-protopyropheophorbide a (zinc
      porphyrin 3), was kinetically analyzed under acidic conditions to examine the
      effects of macrocyclic structures on demetalation without peripheral substitution
      effects. Zinc bacteriochlorin 1 exhibited much slower demetalation kinetics than
      zinc chlorin 2 and zinc porphyrin 3. These results indicate that the
      bacteriochlorin skeleton provides significant resistance to the removal of the
      central metal from the tetrapyrrole ligand. Comparison of demetalation kinetics
      of 3-acetyl zinc complexes 2 and 3 with that of 3-vinyl zinc complexes under the
      same reaction condition demonstrated that the relative ratio (5.0 * 10(-2)) of
      the demetalation rate constant of the 3-acetyl zinc chlorin 2 to that of the
      corresponding 3-vinyl zinc chlorin 4 resembled the case of the 3-acetyl zinc
      porphyrin 3 to the 3-vinyl zinc porphyrin 5 (the relative ratio was 6.8 * 10(
      2)). These suggest that the electron-withdrawing 3-acetyl group slows down the
      demetalation from the tetrapyrrole ligands more than the 3-vinyl group and that
      the 3-acetyl effect is analogous in both chlorin and porphyrin pi-systems.

PMID- 21939236
TI  - One-pot synthesis of indole-fused scaffolds via gold-catalyzed tandem annulation
      reactions of 1,2-bis(alkynyl)-2-en-1-ones with indoles.
AB  - The gold-catalyzed tandem cyclization of 1,2-bis(alkynyl)-2-en-1-ones with
      indoles offers an efficient and straightforward route to indole-fused polycyclic
      systems. The process is realized through a cascade carbonyl-yne
      cyclization/Friedel-Crafts/indole-yne cyclization sequence catalyzed by a single
      pot catalyst of gold.

PMID- 21939237
TI  - Fast NMR data acquisition from bicelles containing a membrane-associated peptide
      at natural-abundance.
AB  - In spite of recent technological advances in NMR spectroscopy, its low
      sensitivity continues to be a major limitation particularly for the structural
      studies of membrane proteins. The need for a large quantity of a membrane protein
      and acquisition of NMR data for a long duration are not desirable. Therefore,
      there is considerable interest in the development of methods to speed up the NMR
      data acquisition from model membrane samples. In this study, we demonstrate the
      feasibility of acquiring two-dimensional spectra of an antimicrobial peptide (MSI
      78; also known as pexiganan) embedded in isotropic bicelles using natural
      abundance (15)N nuclei. A copper-chelated lipid embedded in bicelles is used to
      speed-up the spin-lattice relaxation of protons without affecting the spectral
      resolution and thus enabling fast data acquisition. Our results suggest that even
      a 2D SOFAST-HMQC spectrum can be obtained four times faster using a very small
      amount (~3 mM) of a copper-chelated lipid. These results demonstrate that this
      approach will be useful in the structural studies of membrane-associated peptides
      and proteins without the need for isotopic enrichment for solution NMR studies.

PMID- 21939238
TI  - Perchlorate uptake in spinach as related to perchlorate, nitrate, and chloride
      concentrations in irrigation water.
AB  - Several studies have reported on the detection of perchlorate (ClO(4)(-)) in
      edible leafy vegetables irrigated with Colorado River water. However, there is no
      information on spinach as related to ClO(4)(-) in irrigation water nor on the
      effect of other anions on ClO(4)(-) uptake. A greenhouse ClO(4)(-) uptake
      experiment using spinach was conducted to investigate the impact of presence of
      chloride (Cl(-)) and nitrate (NO(3)(-)) on ClO(4)(-) uptake under controlled
      conditions. We examined three concentrations of ClO(4)(-), 40, 220, and 400
      nmol(c)/L (nanomoles of charge per liter of solution), three concentrations of
      Cl(-), 2.5, 13.75, and 25 mmol(c)/L, and NO(3)(-) at 2, 11, and 20 mmol(c)/L. The
      results revealed that ClO(4)(-) was taken up the most when NO(3)(-) and Cl(-)
      were lowest in concentration in irrigation water. More ClO(4)(-) was detected in
      spinach leaves than that in the root tissue. Relative to lettuces, spinach
      accumulated more ClO(4)(-) in the plant tissue. Perchlorate was accumulated in
      spinach leaves more than reported for outer leaves of lettuce at 40 nmol(c)/L of
      ClO(4)(-) in irrigation water. The results also provided evidence that spinach
      selectively took up ClO(4)(-) relative to Cl(-). We developed a predictive model
      to describe the ClO(4)(-) concentration in spinach as related to the Cl(-),
      NO(3)(-), and ClO(4)(-) concentration in irrigation water.

PMID- 21939240
TI  - New method for fabrication of fused silica emitters with submicrometer orifices
      for nanoelectrospray mass spectrometry.
AB  - In this paper, we describe a new method for fabrication of nanoelectrospray
      emitters. The needles were pulled from fused silica capillary tubing, which was
      melted by means of a plasma, formed by electrical discharges between two pointed
      platinum electrodes. A key feature of the pulling device is a rotating
      configuration of the electrodes, which results in an even radial heating of the
      capillary. The construction of the setup is straightforward, and needles with a
      variety of shapes can be fabricated, including orifices of submicrometer
      dimensions. Pulled needles with long tapered tips and an orifice of 0.5 MUm were
      utilized for electrospray ionization mass spectrometry (ESI-MS) of discrete
      sample volumes down to 275 pL. The picoliter-sized samples were transferred into
      the tip of the needle from a silicon microchip by aspiration. To avoid a rapid
      evaporation of the sample, all manipulations were performed under a cover of a
      fluorocarbon liquid. The limit of detection was measured to be ca. 20 attomole
      for insulin (chain B, oxidized).

PMID- 21939241
TI  - Using Si and Ge nanostructures as substrates for surface-enhanced Raman
      scattering based on photoinduced charge transfer mechanism.
AB  - The possibility of utilizing the Si and Ge nanostructures to promote surface
      enhanced Raman scattering (SERS) is discussed. The vibronic coupling of the
      conduction band and valence band states of Si or Ge with the excited and ground
      states of the target molecule during the charge transfer (CT) process could
      enhance the molecular polarizability tensor. Using H-terminated silicon nanowire
      (H-SiNW) and germanium nanotube (H-GeNT) arrays as substrates, significant Raman
      enhancement of the standard probes, Rodamine 6G (R6G), dye
      (Bu(4)N)(2)[Ru(dcbpyH)(2)-(NCS)(2)] (N719), and 4-aminothiophenol (PATP), are
      demonstrated. The abundant hydrogen atoms terminated on the surface of SiNW and
      GeNT arrays play a critical role in promoting efficient CT and enable the SERS
      effect.

PMID- 21939243
TI  - Facile spray-drying assembly of uniform microencapsulates with tunable core-shell
      structures and controlled release properties.
AB  - Microencapsulates with defined core-shell structures are of interest for
      applications, such as controlled release and encapsulation, because of the
      feasibility of fine-tuning individual functionalities of different parts. Here,
      we report a new approach for efficient and scalable production of such particles.
      Eudragit RS (a co-polymer of ethyl acrylate, methyl methacrylate, and a low
      content of methacrylic acid ester with quaternary ammonium groups) was used as
      the main shell component, with silica as the core component, formed upon a single
      step spray-drying assembly. The method is capable of forming uniform core-shell
      particles from homogeneous precursors without the use of any organic solvents.
      Evaporation-induced self-assembly attained the phase separation among different
      components during drying, resulting in the core-shell spatial configuration,
      while precise control over particle uniformity was accomplished via a
      microfluidic jet spray dryer. Direct control over shell thickness can be achieved
      from the ratio of the core and shell ingredients in the precursors. A fluorescent
      compound, rhodamine B, is used as a highly water-soluble model component to
      investigate the controlled release properties of these microencapsulates, with
      the release behaviors shown to be significantly dependent upon their
      architectures.

PMID- 21939244
TI  - ATP-stimulated, DNA-mediated redox signaling by XPD, a DNA repair and
      transcription helicase.
AB  - Using DNA-modified electrodes, we show DNA-mediated signaling by XPD, a helicase
      that contains a [4Fe-4S] cluster and is critical for nucleotide excision repair
      and transcription. The DNA-mediated redox signal resembles that of base excision
      repair proteins, with a DNA-bound redox potential of ~80 mV versus NHE.
      Significantly, this signal increases with ATP hydrolysis. Moreover, the redox
      signal is substrate-dependent, reports on the DNA conformational changes
      associated with enzymatic function, and may reflect a general biological role for
      DNA charge transport.

PMID- 21939245
TI  - Simultaneous parallel and antiparallel self-assembly in a triazole/amide
      macrocycle conformationally homologous to D-,L-alpha-amino acid based cyclic
      peptides: NMR and molecular modeling study.
AB  - A 1,4-linked triazole/amide based peptidomimetic macrocycle, synthesized from a
      triazole amide oligomer of cis-furanoid sugar triazole amino acids, possesses a
      conformation resembling the D-,L-alpha-amino acid based cyclic peptides despite
      having uniform backbone chirality. It undergoes a unique mode of self-assembly
      through an antiparallel backbone to backbone intermolecular H-bonding involving
      amide NH and triazole N2/N3 as well as parallel stacking via amide NH and
      carbonyl oxygen H-bonding, leading to the formation of a tubular nanostructure.

PMID- 21939246
TI  - Belt-shaped pi-systems: relating geometry to electronic structure in a six
      porphyrin nanoring.
AB  - Linear pi-conjugated oligomers have been widely investigated, but the behavior of
      the corresponding cyclic oligomers is poorly understood, despite the recent
      synthesis of pi-conjugated macrocycles such as [n]cycloparaphenylenes and
      cyclo[n]thiophenes. Here we present an efficient template-directed synthesis of a
      pi-conjugated butadiyne-linked cyclic porphyrin hexamer directly from the
      monomer. Small-angle X-ray scattering data show that this nanoring is shape
      persistent in solution, even without its template, whereas the linear porphyrin
      hexamer is relatively flexible. The crystal structure of the nanoring-template
      complex shows that most of the strain is localized in the acetylenes; the
      porphyrin units are slightly curved, but the zinc coordination sphere is
      undistorted. The electrochemistry, absorption, and fluorescence spectra indicate
      that the HOMO-LUMO gap of the nanoring is less than that of the linear hexamer
      and less than that of the corresponding polymer. The nanoring exhibits six one
      electron reductions and six one-electron oxidations, most of which are well
      resolved. Ultrafast fluorescence anisotropy measurements show that absorption of
      light generates an excited state that is delocalized over the whole pi-system
      within a time of less than 0.5 ps. The fluorescence spectrum is amazingly
      structured and red-shifted. A similar, but less dramatic, red-shift has been
      reported in the fluorescence spectra of cycloparaphenylenes and was attributed to
      a high exciton binding energy; however the exciton binding energy of the
      porphyrin nanoring is similar to those of linear oligomers. Quantum-chemical
      excited state calculations show that the fluorescence spectrum of the nanoring
      can be fully explained in terms of vibronic Herzberg-Teller (HT) intensity
      borrowing.

PMID- 21939247
TI  - Real time observation of ultrafast peptide conformational dynamics: molecular
      dynamics simulation vs infrared experiment.
AB  - Employing nonequilibrium molecular dynamics (MD) simulations and transient
      infrared (IR) spectroscopy, a joint theoretical/experimental study on a water
      soluble photoswitchable octapeptide designed by Renner et al. [Biopolymers 2002,
      63, 382] is presented. The simulations predict the cooling of the hot
      photoproducts on a time scale of 7 ps and complex conformational rearrangements
      ranging from a few picoseconds to several nanoseconds. The experiments yield a
      dominant fast relaxation time of 5 ps, which is identified as the cooling time of
      the peptide in water and also accounts for initial conformational changes of the
      system. Moreover, a weaker component of 300 ps is found, which reflects the
      overall conformational relaxation of the system. The virtues and the limitations
      of the joint MD/IR approach to describe biomolecular conformational
      rearrangements are discussed.

PMID- 21939248
TI  - Fullerene- and pyromellitdiimide-appended tripodal ligands embedded in light
      harvesting porphyrin macrorings.
AB  - Three new tripyridyl tripodal ligands appended with either fullerene or
      pyromellitdiimide moieties, named C(60)-s-Tripod, C(60)-l-Tripod, and PI-Tripod,
      were synthesized and introduced into a porphyrin macroring N-(1-Zn)(3) (where 1
      Zn = trisporphyrinatozinc(II)). From UV-vis absorption and fluorescence titration
      data, the binding constants of C(60)-s-Tripod, C(60)-l-Tripod, and PI-Tripod with
      N-(1-Zn)(3) in benzonitrile were estimated to be 3 * 10(8), 1 * 10(7), and 2 *
      10(7) M(-1), respectively. These large binding constants denote multiple
      interactions of the ligands to N-(1-Zn)(3). The binding constants of the longer
      ligand (C(60)-l-Tripod) and the pyromellitdiimide ligand (PI-Tripod) are almost
      the same as those without the fullerene or pyromellitdiimide groups, indicating
      that they interact via three pyridyl groups to the porphyrinatozinc(II)
      coordination. In contrast, the larger binding constants and the almost complete
      fluorescence quenching in the case of the shorter ligand (C(60)-s-Tripod)
      indicate that the interaction with N-(1-Zn)(3) is via two pyridyl groups to the
      porphyrinatozinc(II) coordination and a pi-pi interaction of the fullerene to the
      porphyrin(s). The fluorescence of N-(1-Zn)(3) was quenched by up to 80% by the
      interaction of C(60)-l-Tripod. The nanosecond transient absorption spectra showed
      only the excited triplet peak of the fullerene on selective excitation of the
      macrocyclic porphyrins, indicating that energy transfer from the excited N-(1
      Zn)(3) group to the fullerenyl moiety occurs in the C(60)-l-Tripod/N-(1-Zn)(3)
      composite. In the case of PI-Tripod, the fluorescence of N-(1-Zn)(3) was quenched
      by 45%. It seems that the fluorescence quenching probably originates from
      electron transfer from the excited N-(1-Zn)(3) group to the pyromellitdiimide
      moiety.

PMID- 21939239
TI  - Regulation of mammalian physiology, development, and disease by the sphingosine 1
      phosphate and lysophosphatidic acid receptors.

PMID- 21939249
TI  - Femtosecond dynamics of the ring closing process of diarylethene: a case study of
      electrocyclic reactions in photochromic single crystals.
AB  - The cyclization reaction of the photochromic diarylethene derivative 1,2-bis(2,4
      dimethyl-5-phenyl-3-thienyl)perfluorocyclopentene was studied in its single
      crystal phase with femtosecond transient absorption spectroscopy. The transient
      absorption measurements were performed with a robust acquisition scheme that
      explicitly exploits the photoreversibility of the molecular system and monitors
      the reversibility conditions. The crystalline system demonstrated 3 * 10(4)
      repeatable cycles before significant degradation was observed. Immediately
      following photoexcitation, the excited state absorption associated with the open
      ring conformation undergoes a large spectral shift with a time constant of
      approximately 200 fs. Following this evolution on the excited state potential
      energy surface, the ring closure occurs with a time constant of 5.3 ps, which is
      significantly slower than previously reported measurements for similar
      derivatives in the solution phase. Time resolved electron diffraction studies
      were used to further demonstrate the assignment of the transient absorption
      dynamics to the ring closing reaction. The mechanistic details of the ring
      closing are discussed in the context of prior computational work along with a
      vibrational mode analysis using density functional theory to give some insight
      into the primary motions involved in the ring closing reaction.

PMID- 21939250
TI  - Tandem visible light-mediated radical cyclization-divinylcyclopropane
      rearrangement to tricyclic pyrrolidinones.
AB  - Visible light promoted single electron reduction of bromocyclopropyl cyclization
      scaffolds enabled by photoredox catalysis initiates a novel tandem radical
      cyclization/sigmatropic rearrangement to generate tricyclic pyrrolidinones having
      considerable molecular complexity from simple, readily available starting
      materials. Furthermore, subtle variations to substrate structure afford a wide
      array of reaction diversity.

PMID- 21939251
TI  - Quantification of a single aggregate inner porosity and pore accessibility using
      hard X-ray phase-contrast nanotomography.
AB  - The 3D structure of three individual aggregates composed of 165 nm polystyrene
      primary particles is revealed nondestructively by hard X-ray phase-contrast
      synchrotron nanotomography. Three-dimensional image analysis allows us for the
      first time to obtain the complex inner porosity of the entire aggregate. It is
      demonstrated that despite their rather compact structure, characterized by a
      fractal dimension equal to 2.7, the produced aggregates are still porous, with
      porosity increasing with its size. Generated pores have diameters from 100 nm to
      3 MUm and are almost completely interconnected.

PMID- 21939252
TI  - Quantitative measurement of direct nitrous oxide emissions from microalgae
      cultivation.
AB  - Although numerous lifecycle assessments (LCA) of microalgae-based biofuels have
      suggested net reductions of greenhouse gas emissions, limited experimental data
      exist on direct emissions from microalgae cultivation systems. For example,
      nitrous oxide (N(2)O) is a potent greenhouse gas that has been detected from
      microalgae cultivation. However, little quantitative experimental data exist on
      direct N(2)O emissions from microalgae cultivation, which has inhibited LCA
      performed to date. In this study, microalgae species Nannochloropsis salina was
      cultivated with diurnal light-dark cycling using a nitrate nitrogen source.
      Gaseous N(2)O emissions were quantitatively measured using Fourier transform
      infrared spectrometry. Under a nitrogen headspace (photobioreactor simulation),
      the reactors exhibited elevated N(2)O emissions during dark periods, and reduced
      N(2)O emissions during light periods. Under air headspace conditions (open pond
      simulation), N(2)O emissions were negligible during both light and dark periods.
      Results show that N(2)O production was induced by anoxic conditions when nitrate
      was present, suggesting that N(2)O was produced by denitrifying bacteria within
      the culture. The presence of denitrifying bacteria was verified through PCR-based
      detection of norB genes and antibiotic treatments, the latter of which
      substantially reduced N(2)O emissions. Application of these results to LCA and
      strategies for growth management to reduce N(2)O emissions are discussed.

PMID- 21939253
TI  - Farinamycin, a quinazoline from Streptomyces griseus.
AB  - The metabolic potential of a Streptomyces griseus strain was investigated under
      various cultivation conditions. After fermentation in a flour-based medium, a new
      quinazoline metabolite, farinamycin (1), could be isolated from the bacterium,
      which was previously known only for the production of phenoxazinone antibiotics.
      The structure of 1 illuminates the biosynthetic versatility of S. griseus, which
      assembles a defined set of building blocks into structurally diverse natural
      products.

PMID- 21939254
TI  - Molecular order in high-efficiency polymer/fullerene bulk heterojunction solar
      cells.
AB  - We report quantitative measurements of ordering, molecular orientation, and
      nanoscale morphology in the active layer of bulk heterojunction (BHJ) organic
      photovoltaic cells based on a thieno[3,4-b]thiophene-alt-benzodithiophene
      copolymer (PTB7), which has been shown to yield very high power conversion
      efficiency when blended with [6,6]-phenyl-C71-butyric acid methyl ester
      (PC(71)BM). A surprisingly low degree of order was found in the polymer-far lower
      in the bulk heterojunction than in pure PTB7. X-ray diffraction data yielded a
      nearly full orientation distribution for the polymer pi-stacking direction within
      well-ordered regions, revealing a moderate preference for pi-stacking in the
      vertical direction ("face-on"). By combining molecular orientation information
      from polarizing absorption spectroscopies with the orientation distribution of
      ordered material from diffraction, we propose a model describing the PTB7
      molecular orientation distribution (ordered and disordered), with the fraction of
      ordered polymer as a model parameter. This model shows that only a small fraction
      (~20%) of the polymer in the PTB7/PC(71)BM blend is ordered. Energy-filtered
      transmission electron microscopy shows that the morphology of PTB7/PC(71)BM is
      composed of nanoscale fullerene-rich aggregates separated by polymer-rich
      regions. The addition of diiodooctane (DIO) to the casting solvent, as a
      processing additive, results in smaller domains and a more finely
      interpenetrating BHJ morphology, relative to blend films cast without DIO.

PMID- 21939255
TI  - Electronic interpretation of conformational preferences in benzyl derivatives and
      related compounds.
AB  - Quantum Theory of Atoms in Molecules (QTAIM) analysis on B3LYP/6-311++G(2d,2p) 6d
      electron densities of five benzyl derivatives (C(6)H(5)-CH(2)X; X = F, Cl, OH,
      SH, NH(2)) and seven related fluorides of furan, pyrrole, and naphthalene
      indicates that the preference for perpendicular or gauche conformation exhibited
      by these compounds is related to the diminution of the steric repulsion between
      the heteroatom at the substituent and the closest hydrogen in the ring. The
      electron density reorganization can be satisfactorily explained on the basis of
      these repulsive interactions, while no evidence of larger hyperconjugative
      delocalization is observed in the preferred conformations.

PMID- 21939256
TI  - Role of long-range intermolecular forces in the formation of inorganic
      nanoparticle clusters.
AB  - An understanding of the role played by intermolecular forces in terms of the
      electron density distribution is fundamental to the understanding of the self
      assembly of molecules in the formation of a molecular crystal. Using ab initio
      methods capable of describing both short-range intramolecular interactions and
      long-range London dispersion interactions arising from electron correlation,
      analyses of inorganic dimers of As(4)S(4) and As(4)O(6) molecules cut from the
      structures of realgar and arsenolite, respectively, reveal that the molecules
      adopt a configuration that closely matches that observed for the crystal.
      Decomposition of the interaction energies using symmetry-adapted perturbation
      theory reveals that both model dimers feature significant stabilization from
      electrostatic forces as anticipated by a Lewis acid/Lewis base picture of the
      interaction. London dispersion forces also contribute significantly to the
      interaction, although they play a greater role in the realgar structure near
      equilibrium than in arsenolite.

PMID- 21939257
TI  - QTAIM application in drug development: prediction of relative stability of drug
      polymorphs from experimental crystal structures.
AB  - Prediction of the most stable crystal form based on the strongest intermolecular
      hydrogen bonds (HBs) only, was successfully applied to ten polymorphic drug
      systems, using the Quantum Theory of Atoms in Molecules (QTAIM). The results of
      the predictions were demonstrated to be superior to the thermodynamic stability
      ranking based on molecular mechanical (COMPASS forcefield), DFT and DFT-D
      calculations, as well as on the QTAIM predictions based on the total
      intermolecular HBing interactions strength. The obtained results support the
      validity of the best donor/best acceptor hierarchical approach for polymorph
      stability analysis of drug-like molecules: weak interactions are not as important
      for stability ranking as the strongest HBs. In addition, the proposed QTAIM
      approach allowed a reasonable ranking of the relative stability of multiple
      polymorphic crystalline forms of two test systems, axitinib and sulfathiazole.

PMID- 21939259
TI  - How insoluble particles affect the solutions' conductivity: a theory and the test
      in NaCl and chitosan solutions.
AB  - In this study, we formalize a theory about how insoluble particles in the
      solution affect the solution electrical conductivity. We propose four corollaries
      of this theory: (1) the conductivity change is the same as long as the
      concentration of particles exceeds a certain value; (2) the solution conductivity
      is irrelevant to the particle size; (3) the increasing temperature weakens the
      particles' effect on solution conductivity; (4) the heavier the ions in solutions
      are, the larger the conductivity change caused by particles is. We then prove
      these four corollaries to be right by experiments in two solution systems, NaCl +
      CaCO(3) and chitosan + nHAC (nanohydroxyapatite/collagen composite).

PMID- 21939258
TI  - N-PEGylation of a reverse turn is stabilizing in multiple sequence contexts,
      unlike N-GlcNAcylation.
AB  - The intrinsic stabilization of therapeutic proteins by N-glycosylation can endow
      them with increased shelf and serum half-lives owing to lower populations of
      misfolded and unfolded states, which are susceptible to aggregation and
      proteolysis. Conjugation of poly(ethylene glycol) (PEG) oligomers to nucleophilic
      groups on the surfaces of folded proteins (i.e., PEGylation) is a chemical
      alternative to N-glycosylation, in that it can also enhance the pharmacologic
      attributes of therapeutic proteins. However, the energetic consequences of
      PEGylation are currently not predictable. We find that PEGylation of an Asn
      residue in reverse turn 1 of the Pin WW domain is intrinsically stabilizing in
      several sequence contexts, unlike N-glycosylation, which is only stabilizing in a
      particular sequence context. Our thermodynamic data are consistent with the
      hypothesis that PEGylation destabilizes the protein denatured state ensemble via
      an excluded volume effect, whereas N-glycosylation-associated stabilization
      results primarily from native state interactions between the N-glycan and the
      protein.

PMID- 21939260
TI  - Biophysical investigations on the interaction of the major bovine seminal plasma
      protein, PDC-109, with heparin.
AB  - PDC-109, the major bovine seminal plasma protein, binds to sperm plasma membrane
      and modulates capacitation in the presence of heparin. In view of this, the PDC
      109/heparin interaction has been investigated employing various biophysical
      approaches. Isothermal titration calorimetric studies yielded the association
      constant and changes in enthalpy and entropy for the interaction at 25  degrees C
      (pH 7.4) as 1.92 (+/-0.2) * 10(5) M(-1), 18.6 (+/-1.6) kcal M(-1), and 86.5 (+/
      5.1) cal M(-1) K(-1), respectively, whereas differential scanning calorimetric
      studies indicated that heparin binding results in a significant increase in the
      thermal stability of PDC-109. The affinity decreases with increase in pH and
      ionic strength, consistent with the involvement of electrostatic forces in this
      interaction. Circular dichroism spectroscopic studies indicated that PDC-109
      retains its conformational features even up to 70-75  degrees C in the presence
      of heparin, whereas the native protein unfolds at about 55  degrees C. Atomic
      force microscopic studies demonstrated that large oligomeric structures are
      formed upon binding of PDC-109 to heparin, indicating an increase in the local
      density of the protein, which may be relevant to the ability of heparin to
      potentiate PDC-109 induced sperm capacitation.

PMID- 21939261
TI  - Plasmon dynamics in colloidal Cu2-xSe nanocrystals.
AB  - The optical response of metallic nanostructures after intense excitation with
      femtosecond-laser pulses has recently attracted increasing attention: such
      response is dominated by ultrafast electron-phonon coupling and offers the
      possibility to achieve optical modulation with unprecedented terahertz bandwidth.
      In addition to noble metal nanoparticles, efforts have been made in recent years
      to synthesize heavily doped semiconductor nanocrystals so as to achieve a
      plasmonic behavior with spectrally tunable features. In this work, we studied the
      dynamics of the localized plasmon resonance exhibited by colloidal Cu(2-x)Se
      nanocrystals of 13 nm in diameter and with x around 0.15, upon excitation by
      ultrafast laser pulses via pump-probe experiments in the near-infrared, with ~200
      fs resolution time. The experimental results were interpreted according to the
      two-temperature model and revealed the existence of strong nonlinearities in the
      plasmonic absorption due to the much lower carrier density of Cu(2-x)Se compared
      to noble metals, which led to ultrafast control of the probe signal with
      modulation depth exceeding 40% in transmission.

PMID- 21939263
TI  - Highly conducting pi-conjugated molecular junctions covalently bonded to gold
      electrodes.
AB  - We measure electronic conductance through single conjugated molecules bonded to
      Au metal electrodes with direct Au-C covalent bonds using the scanning tunneling
      microscope based break-junction technique. We start with molecules terminated
      with trimethyltin end groups that cleave off in situ, resulting in formation of a
      direct covalent sigma bond between the carbon backbone and the gold metal
      electrodes. The molecular carbon backbone used in this study consist of a
      conjugated pi system that has one terminal methylene group on each end, which
      bonds to the electrodes, achieving large electronic coupling of the electrodes to
      the pi system. The junctions formed with the prototypical example of 1,4
      dimethylenebenzene show a conductance approaching one conductance quantum (G(0) =
      2e(2)/h). Junctions formed with methylene-terminated oligophenyls with two to
      four phenyl units show a 100-fold increase in conductance compared with junctions
      formed with amine-linked oligophenyls. The conduction mechanism for these longer
      oligophenyls is tunneling, as they exhibit an exponential dependence of
      conductance on oligomer length. In addition, density functional theory based
      calculations for the Au-xylylene-Au junction show near-resonant transmission,
      with a crossover to tunneling for the longer oligomers.

PMID- 21939262
TI  - Complexes of native ubiquitin and dodecyl sulfate illustrate the nature of
      hydrophobic and electrostatic interactions in the binding of proteins and
      surfactants.
AB  - A previous study, using capillary electrophoresis (CE) [J. Am. Chem. Soc. 2008,
      130, 17384-17393], reported that six discrete complexes of ubiquitin (UBI) and
      sodium dodecyl sulfate (SDS) form at different concentrations of SDS along the
      pathway to unfolding of UBI in solutions of SDS. One complex (which formed
      between 0.8 and 1.8 mM SDS) consisted of native UBI associated with approximately
      11 molecules of SDS. The current study used CE and (15)N/(13)C-(1)H heteronuclear
      single quantum coherence (HSQC) NMR spectroscopy to identify residues in folded
      UBI that associate specifically with SDS at 0.8-1.8 mM SDS, and to correlate
      these associations with established biophysical and structural properties of this
      well-characterized protein. The ability of the surface charge and hydrophobicity
      of folded UBI to affect the association with SDS (at concentrations below the
      CMC) was studied, using CE, by converting lys-epsilon-NH(3)(+) to lys-epsilon
      NHCOCH(3) groups. According to CE, the acetylation of lysine residues inhibited
      the binding of 11 SDS ([SDS] < 2 mM) and decreased the number of complexes of
      composition UBI-(NHAc)(8).SDS(n) that formed on the pathway of unfolding of UBI
      (NHAc)(8) in SDS. A comparison of (15)N-(1)H HSQC spectra at 0 mM and 1 mM SDS
      with calculated electrostatic surface potentials of folded UBI (e.g., solutions
      to the nonlinear Poisson-Boltzmann (PB) equation) suggested, however, that SDS
      binds preferentially to native UBI at hydrophobic residues that are formally
      neutral (i.e., Leu and Ile), but that have positive electrostatic surface
      potential (as predicted from solutions to nonlinear PB equations); SDS did not
      uniformly interact with residues that have formal positive charge (e.g., Lys or
      Arg). Cationic functional groups, therefore, promote the binding of SDS to folded
      UBI because these groups exert long-range effects on the positive electrostatic
      surface potential (which extend beyond their own van der Waals radii, as
      predicted from PB theory), and not because cationic groups are necessarily the
      site of ionic interactions with sulfate groups. Moreover, SDS associated with
      residues in native UBI without regard to their location in alpha-helix or beta
      sheet structure (although residues in hydrogen-bonded loops did not bind SDS). No
      correlation was observed between the association of an amino acid with SDS and
      the solvent accessibility of the residue or its rate of amide H/D exchange. This
      study establishes a few (of perhaps several) factors that control the
      simultaneous molecular recognition of multiple anionic amphiphiles by a folded
      cytosolic protein.

PMID- 21939264
TI  - Radical stabilization is crucial in the mechanism of action of lysine 5,6
      aminomutase: role of tyrosine-263alpha as revealed by electron paramagnetic
      resonance spectroscopy.
AB  - Adenosylcobalamin- and pyridoxal-5'-phosphate-dependent lysine 5,6-aminomutase
      utilizes free radical intermediates to mediate 1,2-amino group rearrangement,
      during which an elusive high-energy aziridincarbinyl radical is proposed to be
      central in the mechanism of action. Understanding how the enzyme participates in
      stabilizing any of the radical intermediates is fundamentally significant. Y263F
      mutation abolished the enzymatic activity. With isotope-edited EPR methods, the
      roles of the Tyr263alpha residue in the putative active site are revealed. The
      Tyr263alpha residue stabilizes a radical intermediate, which most likely is the
      aziridincarbinyl radical, either by acting as a spin-relay device or serving as
      an anchor for the pyridine ring of pyridoxal-5'-phosphate through aromatic pi
      stacking interactions during spin transfer. The Tyr263alpha residue also protects
      the radical intermediate from interception by molecular oxygen. This study
      supports the proposed reaction mechanism, including the aziridincarbinyl radical,
      which has eluded detection for more than two decades.

PMID- 21939265
TI  - High-resolution solid-state 2H NMR spectroscopy of polymorphs of glycine.
AB  - High-resolution solid-state (2)H MAS NMR studies of the alpha and gamma
      polymorphs of fully deuterated glycine (glycine-d(5)) are reported. Analysis of
      spinning sideband patterns is used to determine the (2)H quadrupole interaction
      parameters, and is shown to yield good agreement with the corresponding
      parameters determined from single-crystal (2)H NMR measurements (the maximum
      deviation in quadrupole coupling constants determined from these two approaches
      is only 1%). From analysis of simulated (2)H MAS NMR sideband patterns as a
      function of reorientational jump frequency (kappa) for the -N(+)D(3) group in
      glycine-d(5), the experimentally observed differences in the (2)H MAS NMR
      spectrum for the -N(+)D(3) deutrons in the alpha and gamma polymorphs is
      attributed to differences in the rate of reorientation of the -N(+)D(3) group.
      These simulations show severe broadening of the (2)H MAS NMR signal in the
      intermediate motion regime, suggesting that deuterons undergoing reorientational
      motions at rates in the range kappa ~ 10(4)-10(6) s(-1) are likely to be
      undetectable in (2)H MAS NMR measurements for materials with natural isotopic
      abundances. The (1)H NMR chemical shifts for the alpha and gamma polymorphs of
      glycine have been determined from the (2)H MAS NMR results, taking into account
      the known second-order shift. Further quantum mechanical calculations of (2)H
      quadrupole interaction parameters and (1)H chemical shifts reveal the structural
      dependence of these parameters in the two polymorphs and suggest that the
      existence of two short intermolecular C-H...O contacts for one of the H atoms of
      the >CH(2) group in the alpha polymorph have a significant influence on the (2)H
      quadrupole coupling and (1)H chemical shift for this site.

PMID- 21939266
TI  - New insights into the reaction paths of hydroxyl radicals with 2'-deoxyguanosine.
AB  - The reaction of HO(*) radical with 2'-deoxyguanosine is intensively studied as a
      model for DNA damage. Several aspects related to the reaction paths responsible
      for the most relevant lesions are not well understood. We have reinvestigated the
      reaction of HO(*) with 2'-deoxyguanosine by pulse radiolysis and extended our
      studies to a variety of substituted derivatives. The main path of hydrogen
      abstraction was confirmed to be from the exocyclic NH(2) group, followed by a
      water-assisted tautomerization. The rate constant (k = 2.3 * 10(4) s(-1))
      obtained from the spectral changes at 620 nm is influenced by the substituent at
      the C8 position. When N1-H is replaced by N1-CH(3), the tautomerization does not
      occur. The spectral changes at 370 nm that correspond to a rate constant of 6.9 *
      10(5) s(-1) were assigned to the cyclization of 2'-deoxyguanosin-5'-yl radical
      with formation of 5',8-cyclo-2'-deoxyguanosine as the product. When NEt(2)
      replaces the exocyclic NH(2), the spectral changes at all wavelengths follow
      second-order kinetics, suggesting a "slow" ring-opening of the 8-hydroxyl adduct
      of 2'-deoxyguanosine.

PMID- 21939267
TI  - 4-Hydroxybenzyl modification of the highly teratogenic retinoid, 4-[(1E)-2
      (5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-1-propen-1-yl]benzoic
      acid (TTNPB), yields a compound that induces apoptosis in breast cancer cells and
      shows reduced teratogenicity.
AB  - Retinoids are a class of compounds with structural similarity to vitamin A. These
      compounds inhibit the proliferation of many cancer cell lines but have had
      limited medical application as they are often toxic at therapeutic levels.
      Efforts to synthesize retinoids with a greater therapeutic index have met with
      limited success. 4-[(1E)-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2
      naphthalenyl)-1-propen-1-yl]benzoic acid (TTNPB) is one of the most biologically
      active all-trans-retinoic acid (atRA) analogues and is highly teratogenic. In
      this study, we show that modification of the TTNPB carboxyl group with an N-(4
      hydroxyphenyl)amido (4HPTTNPB) or a 4-hydroxybenzyl (4HBTTNPB) group changes the
      activity of the compound in cell culture and in vivo. Unlike TTNPB, both
      compounds induce apoptosis in cancer cells and bind poorly to the retinoic acid
      receptors (RARs). Like the similarly modified all-trans-retinoic acid (atRA)
      analogues N-(4-hydroxyphenyl)retinamide (4-HPR/fenretinide) and 4
      hydroxybenzylretinone (4-HBR), 4HBTTNPB is a potent activator of components of
      the ER stress pathway. The amide-linked analogue, 4HPTTNPB, is less toxic to
      developing embryos than the parent TTNPB, and most significantly, the 4
      hydroxybenzyl-modified compound (4HBTTNPB) that cannot be hydrolyzed in vivo to
      the parent TTNPB compound is nearly devoid of teratogenic liability.

PMID- 21939268
TI  - Chemical and enzymatic reductive activation of acylfulvene to isomeric cytotoxic
      reactive intermediates.
AB  - Acylfulvenes (AFs), a class of semisynthetic analogues of the sesquiterpene
      natural product illudin S, are cytotoxic toward cancer cells. The minor
      structural changes between illudin S and AFs translate to an improved therapeutic
      window in preclinical cell-based assays and xenograft models. AFs are, therefore,
      unique tools for addressing the chemical and biochemical basis of cytotoxic
      selectivity. AFs elicit cytotoxic responses by alkylation of biological targets,
      including DNA. While AFs are capable of direct alkylation, cytosolic reductive
      bioactivation to an electrophilic intermediate is correlated with enhanced
      cytotoxicity. Data obtained in this study illustrate chemical aspects of the
      process of AF activation. By tracking reaction mechanisms with stable isotope
      labeled reagents, enzymatic versus chemical activation pathways for AF were
      compared for reactions involving the NADPH-dependent enzyme prostaglandin
      reductase 1 (PTGR1) or sodium borohydride, respectively. These two processes
      resulted in isomeric products that appear to give rise to similar patterns of DNA
      modification. The chemically activated isomer has been newly isolated and
      chemically characterized in this study, including an assessment of its relative
      stereochemistry and stability at varying pH and under bioassay conditions. In
      mammalian cancer cells, this chemically activated analogue was shown to not rely
      on further cellular activation to significantly enhance cytotoxic potency, in
      contrast to the requirements of AF. On the basis of this study, we anticipate
      that the chemically activated form of AF will serve as a useful chemical probe
      for evaluating biomolecular interactions independent of enzyme-mediated
      activation.

PMID- 21939269
TI  - Polycondensation of butenediol: synthesis of telechelic 2-butene-1,4-diol
      oligomers.
AB  - The catalytic condensation of cis-2-butene-1,4-diol with CpRu(MQA)(C(3)H(5)) (Cp
      = cyclopentadienyl, MQA = 4-methoxyquinoline-2-carboxylate) generates poly(2
      butenediol), an unsaturated telechelic polyether diol with molecular weights
      between 400 and 4600 g/mol. This Ru(IV) allyl catalyst enchains 2-butene-1,4-diol
      primarily as the linear trans-2-butenyl ether (92%) along with vinyl branches
      (8%). These telechelic oligomers are useful chain extenders and macromonomers, as
      demonstrated by their use in the synthesis of poly(lactide)-b-poly(butenediol)-b
      poly(lactide) triblock copolymers. Model studies support a proposed mechanism
      involving the formation of Ru(IV) allyl intermediates from allylic alcohols and
      chain growth by selective nucleophilic displacement at the terminus of the Ru(IV)
      allyl to generate trans-2-butenyl ether linkages.

PMID- 21939270
TI  - Electron transfer within nitrogenase: evidence for a deficit-spending mechanism.
AB  - The reduction of substrates catalyzed by nitrogenase utilizes an electron
      transfer (ET) chain comprised of three metalloclusters distributed between the
      two component proteins, designated as the Fe protein and the MoFe protein. The
      flow of electrons through these three metalloclusters involves ET from the [4Fe
      4S] cluster located within the Fe protein to an [8Fe-7S] cluster, called the P
      cluster, located within the MoFe protein and ET from the P cluster to the active
      site [7Fe-9S-X-Mo-homocitrate] cluster called FeMo-cofactor, also located within
      the MoFe protein. The order of these two electron transfer events, the relevant
      oxidation states of the P-cluster, and the role(s) of ATP, which is obligatory
      for ET, remain unknown. In the present work, the electron transfer process was
      examined by stopped-flow spectrophotometry using the wild-type MoFe protein and
      two variant MoFe proteins, one having the beta-188(Ser) residue substituted by
      cysteine and the other having the beta-153(Cys) residue deleted. The data support
      a "deficit-spending" model of electron transfer where the first event (rate
      constant 168 s(-1)) is ET from the P cluster to FeMo-cofactor and the second,
      "backfill", event is fast ET (rate constant >1700 s(-1)) from the Fe protein [4Fe
      4S] cluster to the oxidized P cluster. Changes in osmotic pressure reveal that
      the first electron transfer is conformationally gated, whereas the second is not.
      The data for the beta-153(Cys) deletion MoFe protein variant provide an argument
      against an alternative two-step "hopping" ET model that reverses the two ET
      steps, with the Fe protein first transferring an electron to the P cluster, which
      in turn transfers an electron to FeMo-cofactor. The roles for ATP binding and
      hydrolysis in controlling the ET reactions were examined using betagamma
      methylene-ATP as a prehydrolysis ATP analogue and ADP + AlF(4)(-) as a
      posthydrolysis analogue (a mimic of ADP + P(i)).

PMID- 21939271
TI  - Atomic force microscopy based tunable local anodic oxidation of graphene.
AB  - We have fabricated graphene/graphene oxide/graphene (G/GO/G) junctions by local
      anodic oxidation lithography using atomic force microscopy (AFM). The conductance
      of the G/GO/G junction decreased with the bias voltage applied to the AFM
      cantilever V(tip). For G/GO/G junctions fabricated with large and small |V(tip)|.
      GO was semi-insulating and semiconducting, respectively. AFM-based LAO
      lithography can be used to locally oxidize graphene with various oxidation levels
      and achieve tunability from semiconducting to semi-insulating GO.

PMID- 21939272
TI  - Brillouin scattering investigation of solvation dynamics in succinonitrile
      lithium salt plastic crystalline electrolytes.
AB  - Temperature dependent Brillouin scattering studies have been performed to
      ascertain the influence of solvent dynamics on ion-transport in succinonitrile
      lithium salt plastic crystalline electrolytes. Though very rarely employed, we
      observe that Brillouin spectroscopy is an invaluable tool for investigation of
      solvent dynamics. Analysis of various acoustic (long wavelength) phonon modes
      observed in the Brillouin scattering spectra reveal the influence of trans-gauche
      isomerism and as well as ion-association effects on ion transport. Although
      pristine SN and dilute SN-LiClO(4) samples show only the bulk longitudinal
      acoustic (LA) mode, concentrated SN-LiClO(4) (~0.3-1 M) electrolytes display both
      the bulk LA mode as well as salt induced brillouin modes at ambient temperature.
      The appearance of more than one brillouin mode is attributed to the scattering of
      light from regions with different compressibilities ("compactness").
      Correspondingly, these modes show a large decrease in the full width at half
      maximum (abbreviated as nu(f)) as the temperature decreases. Anomalous
      temperature dependent behavior of nu(f) with addition of salt could be attributed
      to the presence of disorder or strong coupling with a neighbor. The shape of the
      spectrum was evaluated using a Lorentzian and Fano line shape function depending
      on the nature and behavior of the Brillouin modes.

PMID- 21939273
TI  - Selective, room-temperature transformation of methane to C1 oxygenates by deep UV
      photolysis over zeolites.
AB  - Methane can directly be transformed into liquid C(1) oxygenated products with
      selectivities above 95% at 13% conversion by deep UV photocatalysis, in the
      presence of H(2)O and air. Pure silica zeolites, and more specifically, beta
      zeolite with a large number of internal silanol groups is active and selective,
      while amorphous silica with no micropores is much less efficient. Irradiation
      produces the homolytic cleavage of surface hydroxyl groups, leading to silyloxyl
      radicals that will generate methyl radicals from methane. The selectivity arises
      from the occurrence of the reaction in a confined space restricting the mobility
      of the radical intermediates that will be mostly attached to the solid surface.
      Energy consumption of the process is in the order of 7.2 Gcal * mol(-1) that
      compares very favorably with the energy required for transforming methane to
      synthesis gas (15.96 Gcal * mol(-1)).

PMID- 21939274
TI  - Oxidative metabolism of a quinoxaline derivative by xanthine oxidase in rodent
      plasma.
AB  - As part of efforts directed at the G protein-coupled receptor 119 agonist program
      for type 2 diabetes, a series of cyanopyridine derivatives exemplified by
      isopropyl-4-(3-cyano-5-(quinoxalin-6-yl)pyridine-2-yl)piperazine-1-carboxylate
      (1) were identified as novel chemotypes worthy of further hit-to-lead
      optimization. Compound 1, however, was found to be unstable in plasma (37 
      degrees C, pH 7.4) from rat (T(1/2) = 16 min), mouse (T(1/2) = 61 min), and
      guinea pig (T(1/2) = 4 min). Lowering the temperature of plasma incubations (4-25
      degrees C) attenuated the degradation of 1, implicating the involvement of an
      enzyme-mediated process. Failure to detect any appreciable amount of 1 in plasma
      samples from protein binding and pharmacokinetic studies in rats was consistent
      with its labile nature in plasma. Instability noted in rodent plasma was not
      observed in plasma from dogs, monkeys, and humans (T(1/2) > 370 min at 37 
      degrees C, pH 7.4). Metabolite identification studies in rodent plasma revealed
      the formation of a single metabolite (M1), which was 16 Da higher than the
      molecular weight of 1 (compound 1, MH(+) = 403; M1, MH(+) = 419). Pretreatment of
      rat plasma with allopurinol, but not raloxifene, abolished the conversion of 1 to
      M1, suggesting that xanthine oxidase (XO) was responsible for the oxidative
      instability. Consistent with the known catalytic mechanism of XO, the source of
      oxygen incorporated in M1 was derived from water rather than molecular oxygen.
      The formation of M1 was also demonstrated in incubations of 1 with purified
      bovine XO. The structure of M1 was determined by NMR analysis to be isopropyl-4
      (3-cyano-5-(3-oxo-3,4-dihydroquinoxalin-6-yl)pyridine-2-yl)piperazine-1
      carboxylate. The regiochemistry of quinoxaline ring oxidation in 1 was consistent
      with ab initio calculations and molecular docking studies using a published
      crystal structure of bovine XO. A close-in analogue of 1, which lacked the
      quinoxaline motif (e.g., 5-(4-cyano-3-methylphenyl)-2-(4-(3-isopropyl-1,2,4
      oxadiazol-5-yl)piperidin-1-yl)nicotinitrile (2)) was stable in rat plasma and
      possessed substantially improved GPR119 agonist properties. To the best of our
      knowledge, our studies constitute the first report on the involvement of rodent
      XO in oxidative drug metabolism in plasma.

PMID- 21939275
TI  - Wastes generated during the storage of extra virgin olive oil as a natural source
      of phenolic compounds.
AB  - Phenolic compounds in extra virgin olive oil (EVOO) have been associated with
      beneficial effects for health. Indeed, these compounds exert strong
      antiproliferative effects on many pathological processes, which has stimulated
      chemical characterization of the large quantities of wastes generated during
      olive oil production. In this investigation, the potential of byproducts
      generated during storage of EVOO as a natural source of antioxidant compounds has
      been evaluated using solid-liquid and liquid-liquid extraction processes followed
      by rapid resolution liquid chromatography (RRLC) coupled to electrospray time-of
      flight and ion trap mass spectrometry (TOF/IT-MS). These wastes contain
      polyphenols belonging to different classes such as phenolic acids and alcohols,
      secoiridoids, lignans, and flavones. The relationship between phenolic and
      derived compounds has been tentatively established on the basis of proposed
      degradation pathways. Finally, qualitative and quantitative characterizations of
      solid and aqueous wastes suggest that these byproducts can be considered an
      important natural source of phenolic compounds, mainly hydroxytyrosol, tyrosol,
      decarboxymethyl oleuropein aglycone, and luteolin, which, after suitable
      purification, could be used as food antioxidants or as ingredients in
      nutraceutical products due to their interesting technological and pharmaceutical
      properties.

PMID- 21939276
TI  - Orientational control over nitrite reductase on modified gold electrode and its
      effects on the interfacial electron transfer.
AB  - Recently, studies have been reported in which fluorescently labeled redox
      proteins have been studied with a combination of spectroscopy and
      electrochemistry. In order to understand the effect of the dye on the protein
      electrode interaction, voltammetry and surface analysis have been performed on
      protein films of dye-labeled and unlabeled forms of a cysteine-surface variant
      (L93C) and the wild type (wt) of the copper containing nitrite reductase (NiR)
      from  Alcaligenes faecalis  S6. The protein has been adsorbed onto gold
      electrodes modified with self-assembled monolayers (SAMs) made up of 6
      mercaptohexanol (6-OH) and mixtures of various octanethiols. Electrochemical and
      surface-analytical techniques were utilized to explore the influence of the SAM
      composition on wt and L93C NiR enzyme activity and the orientation of the enzyme
      molecules with respect to the electrode/SAM. The unlabeled L93C NiR enzyme is
      only electroactive on mixed SAMs composed of positive 8-aminooctanethiol (8
      NH(2)) and 8-mercaptooctanol (8-OH). No enzymatic activity is observed on SAMs
      consisting of pure 6-OH, 8-OH, or pure 8-NH(2). Modification of L93C NiR with the
      ATTO 565 dye resulted in enzymatic activity on SAMs of 6-OH, but not on SAMs of 8
      OH. Quartz crystal microbalance with dissipation measurements show that well
      ordered and rigid protein films (single orientation of the protein) are formed
      when NiR is electroactive. By contrast, electrode-NiR combinations for which no
      electrochemical activity is observed still have NiR adsorbed on the surfaces, but
      a less-structured and water-rich film is formed. For the unlabeled L93C NiR,
      bilayer formation is observed, suggesting that the Cys93 residue is orientated
      away from the surface and able to form disulfide bridges to a second layer of
      L93C NiR. The results indicate that interfacial electron transfer is only
      possible if the negatively charged surface patch surrounding the electron-entry
      site of NiR is directed toward the electrode. This can be achieved either by
      introducing positive charges in the SAM or, when the SAM does not carry a charge,
      by labeling the enzyme with an ATTO 565 dye, which has some hydrophobic
      character, close to the electron entry site of the NiR.

PMID- 21939277
TI  - Electrochemical and STM studies of 1-thio-beta-D-glucose self-assembled on a
      Au(111) electrode surface.
AB  - In this study, a Au(111) electrode is functionalized with a monolayer of 1-thio
      beta-D-glucose (beta-Tg), producing a hydrophilic surface. A monolayer of beta-Tg
      was formed on a Au(111) surface by either (1) potential-assisted deposition with
      the thiol in a supporting electrolyte or (2) passive incubation of a gold
      substrate in a thiol-containing solution. For each method, the properties of the
      beta-Tg monolayer were investigated using cyclic voltammetry (CV), differential
      capacitance (DC), and chronocoulometry. In addition, electrochemical scanning
      tunneling microscopy (EC-STM) was used to obtain images of the self-assembled
      monolayer with molecular resolution. Potential-assisted assembly of beta-Tg onto
      a Au(111) electrode surface was found to be complicated by oxidation of beta-Tg
      molecules. The EC-STM images revealed formation of a passive layer containing
      honeycomb-like domains characteristic of a formation of S(8) rings, indicating
      the S-C bond may have been cleaved. In contrast, passive self-assembly of
      thioglucose from a methanol solution was found to produce a stable, disordered
      monolayer of beta-Tg. Since the passive assembly method was not complicated by
      the presence of a faradaic process, it is the method of choice for modifying the
      gold surface with a hydrophilic monolayer.

PMID- 21939278
TI  - Influence of the charge relay effect on the silanol condensation reaction as a
      model for silica biomineralization.
AB  - The catalytic effect of various sequential peptides for silica biomineralization
      has been studied. In peptide sequence design, lysine (K) and histidine (H) were
      selected as the standard amino acids and aspartic acid (D) was selected to
      promote the charge relay effects, such as in the enzyme active site. Therefore,
      homopolypeptides (K(10) and H(10)), block polypeptides (K(5)D(5) and H(5)D(5)),
      and alternate polypeptides [(KD)(5) and (HD)(5)] were designed, and the
      dehydration reaction ability of trimethylethoxysilane was investigated as a
      quantitative model of silica mineralization. The catalytic activity per basic
      residue of alternate polypeptide was the highest because of the charge relay
      effects at the surface of the peptide. In silica mineralization using
      tetraethoxysilane, spherical silica particles were obtained, and their size is
      related to the catalytic activities of the peptides in the model systems. From
      these results, the effect of the functional group combination by the peptide
      sequence design enables the control of the efficiency of mineralization and
      preparation of specific inorganic materials.

PMID- 21939279
TI  - Structure and dynamics of poly(oxyethylene) cholesteryl ether wormlike micelles:
      rheometry, SAXS, and cryo-TEM studies.
AB  - In this article, we provide direct evidence for 1-D micellar growth and the
      formation of a network structure in an aqueous system of poly(oxyethylene)
      cholesteryl ether (ChEO(20)) and lauryl diethanolamide (L-02) by rheometry, small
      angle X-ray scattering (SAXS), and cryo-transmission electron microscopy (cryo
      TEM). The ChEO(20) self-assembles into spheroid micelles above the critical
      micelle concentration and undergoes a 1-D microstructural transition upon the
      incorporation of L-02, which because of its lipophilic nature tends to be
      solubilized into the micellar palisade layer and reduces the micellar curvature.
      The elongated micelles entangle with each other, forming network structures of
      wormlike micelles, and the system shows viscoelastic properties, which could be
      described by the Maxwell model. A peak observed in the zero-shear viscosity
      (eta(0)) versus L-02 concentration curve shifted toward higher L-02
      concentrations and the value of maximum viscosity (eta(0 max)) increased with the
      increasing ChEO(20) mixing fraction with water. We observed that eta(0 max)
      increased by 2 to 4 orders of magnitude as a function of the ChEO(20)
      concentration. The Maxwell relaxation time (tau(R)) shows a maximum value at a
      concentration corresponding to eta(0 max) (i.e., tau(R) increases with L-02
      concentration and then decreases after attaining a maximum value, whereas the
      plateau modulus (G(0)) shows monotonous growth). These observations demonstrate
      microstructural transitions in two different modes: L-02 first induces 1-D
      micellar growth and as a result the viscosity increases, and finally after the
      system attains its maximum viscosity, L-02 causes branching in the network
      structures. The microstructure transitions are confirmed by SAXS and cryo-TEM
      techniques.

PMID- 21939280
TI  - Function of UreB in Klebsiella aerogenes urease.
AB  - Urease from Klebsiella aerogenes is composed of three subunits (UreA-UreB-UreC)
      that assemble into a (UreABC)(3) quaternary structure. UreC harbors the dinuclear
      nickel active site, whereas the functions of UreA and UreB remain unknown. UreD
      and UreF accessory proteins previously were suggested to reposition UreB and
      increase the level of exposure of the nascent urease active site, thus
      facilitating metallocenter assembly. In this study, cells were engineered to
      separately produce (UreAC)(3) or UreB, and the purified proteins were
      characterized. Monomeric UreB spontaneously binds to the trimeric heterodimer of
      UreA and UreC to form (UreABC*)(3) apoprotein, as shown by gel filtration
      chromatography, integration of electrophoretic gel band intensities, and mass
      spectrometry. Similar to the authentic urease apoprotein, the active enzyme is
      produced by incubation of (UreABC*)(3) with Ni(2+) and bicarbonate. Conversely,
      UreBDelta1-19, lacking the 19-residue potential hinge and tether to UreC, does
      not form a complex with (UreAC)(3) and yields negligible levels of the active
      enzyme when incubated under activation conditions with (UreAC)(3). Comparison of
      activities and nickel contents for (UreAC)(3), (UreABC*)(3), and (UreABC)(3)
      samples treated with Ni(2+) and bicarbonate and then desalted indicates that UreB
      facilitates efficient incorporation of the metal into the active site and
      protects the bound metal from chelation. Amylose resin pull-down studies reveal
      that MBP-UreD (a fusion of maltose binding protein with UreD) forms complexes
      with (UreABC)(3), (UreAC)(3), and UreB in vivo, but not in vitro. By contrast,
      MBP-UreD does not form an in vivo complex with UreBDelta1-19. The soluble MBP
      UreD-UreF-UreG complex binds in vitro to (UreABC)(3), but not to (UreAC)(3) or
      UreB. Together, these data demonstrate that UreB facilitates the interaction of
      urease with accessory proteins during metallocenter assembly, with the N-terminal
      hinge and tether region being specifically required for this process. In addition
      to its role in urease activation, UreB enhances the stability of UreC against
      proteolytic cleavage.

PMID- 21939281
TI  - Photovoltaic performance of ultrasmall PbSe quantum dots.
AB  - We investigated the effect of PbSe quantum dot size on the performance of
      Schottky solar cells made in an ITO/PEDOT/PbSe/aluminum structure, varying the
      PbSe nanoparticle diameter from 1 to 3 nm. In this highly confined regime, we
      find that the larger particle bandgap can lead to higher open-circuit voltages
      (~0.6 V), and thus an increase in overall efficiency compared to previously
      reported devices of this structure. To carry out this study, we modified existing
      synthesis methods to obtain ultrasmall PbSe nanocrystals with diameters as small
      as 1 nm, where the nanocrystal size is controlled by adjusting the growth
      temperature. As expected, we find that photocurrent decreases with size due to
      reduced absorption and increased recombination, but we also find that the open
      circuit voltage begins to decrease for particles with diameters smaller than 2
      nm, most likely due to reduced collection efficiency. Owing to this effect, we
      find peak performance for devices made with PbSe dots with a first exciton energy
      of ~1.6 eV (2.3 nm diameter), with a typical efficiency of 3.5%, and a champion
      device efficiency of 4.57%. Comparing the external quantum efficiency of our
      devices to an optical model reveals that the photocurrent is also strongly
      affected by the coherent interference in the thin film due to Fabry-Perot cavity
      modes within the PbSe layer. Our results demonstrate that even in this simple
      device architecture, fine-tuning of the nanoparticle size can lead to substantial
      improvements in efficiency.

PMID- 21939283
TI  - Widespread occurrence of bisphenol A in paper and paper products: implications
      for human exposure.
AB  - Bisphenol A (BPA) is used in a variety of consumer products, including some paper
      products, particularly thermal receipt papers, for which it is used as a color
      developer. Nevertheless, little is known about the magnitude of BPA contamination
      or human exposure to BPA as a result of contact with paper and paper products. In
      this study, concentrations of BPA were determined in 15 types of paper products
      (n = 202), including thermal receipts, flyers, magazines, tickets, mailing
      envelopes, newspapers, food contact papers, food cartons, airplane boarding
      passes, luggage tags, printing papers, business cards, napkins, paper towels, and
      toilet paper, collected from several cities in the USA. Thermal receipt papers
      also were collected from Japan, Korea, and Vietnam. BPA was found in 94% of
      thermal receipt papers (n = 103) at concentrations ranging from below the limit
      of quantitation (LOQ, 1 ng/g) to 13.9 mg/g (geometric mean: 0.211 mg/g). The
      majority (81%) of other paper products (n = 99) contained BPA at concentrations
      ranging from below the LOQ to 14.4 MUg/g (geometric mean: 0.016 MUg/g). Whereas
      thermal receipt papers contained the highest concentrations of BPA (milligram-per
      gram), some paper products, including napkins and toilet paper, made from
      recycled papers contained microgram-per-gram concentrations of BPA. Contamination
      during the paper recycling process is a source of BPA in paper products. Daily
      intake (DI) of BPA through dermal absorption was estimated based on the measured
      BPA concentrations and handling frequency of paper products. The daily intake of
      BPA (calculated from median concentrations) through dermal absorption from
      handling of papers was 17.5 and 1300 ng/day for the general population and
      occupationally exposed individuals, respectively; these values are minor compared
      with exposure through diet. Among paper products, thermal receipt papers
      contributed to the majority (>98%) of the exposures.

PMID- 21939284
TI  - Identification and characterization of apelin peptides in bovine colostrum and
      milk by liquid chromatography-mass spectrometry.
AB  - Apelin peptides were recently identified as endogenous ligands of the APJ
      receptor. It has been hypothesized that these peptides are initially provided to
      the newborn by nursing and might be involved in gastrointestinal tract
      development. As apelin peptides may have different effects on the APJ receptor as
      a function of their size, knowledge of their exact structure in early milk is
      essential to clarify their action in gastrointestinal tract development. Bovine
      colostrum is thought to contain high concentrations of a wide diversity of apelin
      peptides, but none of them have yet been rigorously characterized. To identify
      and monitor apelin peptides in bovine colostrum, we developed a cation exchange
      extraction step followed by untargeted liquid chromatography coupled to high
      resolution and high mass accuracy mass spectrometry (LTQ-Orbitrap). Using this
      approach, we characterized 46 endogenous apelin peptides in bovine colostrum,
      which varied in relative abundance from one colostrum to another. Mature as well
      as commercial milk samples were also studied. Taken together, our data
      demonstrate that the multiplicity and variability of apelin peptides are
      biologically relevant and change during milk maturation to reach a more constant
      composition in mature milk.

PMID- 21939285
TI  - Hemorrhagic activity of HF3, a snake venom metalloproteinase: insights from the
      proteomic analysis of mouse skin and blood plasma.
AB  - Hemorrhage induced by snake venom metalloproteinases (SVMPs) is a complex
      phenomenon resulting in capillary disruption and blood extravasation. The
      mechanism of action of SVMPs has been investigated using various methodologies
      however the precise molecular events associated with microvessel disruption
      remains not fully understood. To gain insight into the hemorrhagic process, we
      analyzed the global effects of HF3, an extremely hemorrhagic SVMP from Bothrops
      jararaca, in the mouse skin and plasma. We report that in the HF3-treated skin
      there was evidence of degradation of extracellular matrix (collagens and
      proteoglycans), cytosolic, cytoskeleton, and plasma proteins. Furthermore, the
      data suggest that direct and indirect effects promoted by HF3 contributed to
      tissue injury as the activation of collagenases was detected in the HF3-treated
      skin. In the plasma analysis after depletion of the 20 most abundant proteins,
      fibronectin appeared as degraded by HF3. In contrast, some plasma proteinase
      inhibitors showed higher abundance compared to control skin and plasma. This is
      the first study to assess the complex in vivo effects of HF3 using high
      throughput proteomic approaches, and the results underscore a scenario
      characterized by the interplay between the hydrolysis of intracellular,
      extracellular, and plasma proteins and the increase of plasma inhibitors in the
      hemorrhagic process.

PMID- 21939286
TI  - Computational modeling of the catalytic mechanism of human placental alkaline
      phosphatase (PLAP).
AB  - Alkaline phosphatases (APs) catalyze the hydrolysis and transphosphorylation of
      phosphate monoesters. Quantum mechanical, molecular dynamics, and molecular
      docking techniques were applied to computationally model the catalytic mechanism
      of human placental AP (PLAP). Kinetic and thermodynamic evaluations were
      performed for each reaction step. The functional significances of the more
      important residues within the active site were analyzed. The role of the metal
      ion at the metal binding site M3 was also examined. The calculated activation and
      reaction energy and free energy values obtained suggested the nucleophilic attack
      of the Ser92 alkoxide on the phosphorus atom of the substrate would be the rate
      limiting step of the catalytic hydrolysis of alkyl phosphate monoesters by PLAP.
      The reactivities of the wild-type M3-Mg enzyme and the M3-Zn protein were
      compared, and the main difference observed was a change in the coordination
      number of the M3 metal for the M3-Zn enzyme. This modification in the active site
      structure lowered the free energy profile for the second chemical step of the
      catalytic mechanism (hydrolysis of the covalent phosphoserine intermediate).
      Consequently, a greater stabilization of the phosphoseryl moiety resulted in a
      small increment in the activation free energy of the phosphoserine hydrolysis
      reaction. These computational results suggest that the activation of APs by
      magnesium at the M3 site is caused by the preference of Mg(2+) for octahedral
      coordination, which structurally stabilizes the active site into a catalytically
      most active conformation. The present theoretical results are in good agreement
      with previously reported experimental studies.

PMID- 21939288
TI  - Ferroelectric metal-organic frameworks.

PMID- 21939289
TI  - What is the purpose of the 2011 criteria for fibromyalgia?

PMID- 21939287
TI  - Bioinformatics and systems biology of the lipidome.

PMID- 21939290
TI  - GS-nitroxide (JP4-039)-mediated radioprotection of human Fanconi anemia cell
      lines.
AB  - Fanconi anemia (FA) is an inherited disorder characterized by defective DNA
      repair and cellular sensitivity to DNA crosslinking agents. Clinically, FA is
      associated with high risk for marrow failure, leukemia and head and neck squamous
      cell carcinoma (HNSCC). Radiosensitivity in FA patients compromises the use of
      total-body irradiation for hematopoietic stem cell transplantation and radiation
      therapy for HNSCC. A radioprotector for the surrounding tissue would therefore be
      very valuable during radiotherapy for HNSCC. Clonogenic radiation survival curves
      were determined for pre- or postirradiation treatment with the parent nitroxide
      Tempol or JP4-039 in cells of four FA patient-derived cell lines and two
      transgene-corrected subclonal lines. FancG(-/-) (PD326) and FancD2(-/-) (PD20F)
      patient lines were more sensitive to the DNA crosslinking agent mitomycin C (MMC)
      than their transgene-restored subclonal cell lines (both P < 0.0001). FancD2(-/-)
      cells were more radiosensitive than the transgene restored subclonal cell line (n
      = 2.0 +/- 0.7 and 4.7 +/- 2.2, respectively, P = 0.03). In contrast, FancG(-/-)
      cells were radioresistant relative to the transgene-restored subclonal cell line
      (n = 9.4 +/- 1.5 and 2.2 +/- 05, respectively, P = 0.001). DNA strand breaks
      measured by the comet assay correlated with radiosensitivity. Cell lines from a
      Fanc-C and Fanc-A patients showed radiosensitivity similar to that of Fanc-D2(-/
      ) cells. A fluorophore-tagged JP4-039 (BODIPY-FL) analog targeted the
      mitochondria of the cell lines. Preirradiation or postirradiation treatment with
      JP4-039 at a lower concentration than Tempol significantly increased the
      radioresistance and stabilized the antioxidant stores of all cell lines. Tempol
      increased the toxicity of MMC in FancD2(-/-) cells. These data provide support
      for the potential clinical use of JP4-039 for normal tissue radioprotection
      during chemoradiotherapy in FA patients.

PMID- 21939291
TI  - Mid-pregnancy levels of angiogenic markers as indicators of pathways to preterm
      delivery.
AB  - OBJECTIVE: To determine whether mid-pregnancy levels of angiogenic markers were
      associated with increased risk of preterm delivery (PTD). METHODS: We studied a
      subcohort from the Pregnancy Outcomes and Community Health Study for whom mid
      pregnancy angiogenic markers (soluble fms-like tyrosine kinase-1 [sFlt-1],
      soluble endoglin [sEng] and placental growth factor [PlGF]) and covariate data
      were available (N = 1301). Angiogenic marker levels were grouped as high/not high
      (sFlt-1 and sEng), low/not low (PlGF) and high/intermediate/low (sFlt-1).
      Associations between levels of angiogenic markers and PTD/PTD subtype were
      determined for women who were nonsmokers during pregnancy (N = 933). RESULTS: Low
      PlGF and high sEng were associated with medically-indicated PTD and PTD <35
      weeks, largely due to preeclampsia (PE). Excluding PE and small-for-gestational
      age infants, low sFlt-1 was positively associated with medically-indicated PTD.
      CONCLUSIONS: Among nonsmokers, mid-pregnancy levels of angiogenic markers may
      mark multiple pathways leading to PTD, only one attributable to PE.

PMID- 21939292
TI  - Customized versus population-based growth curves: prediction of low body fat
      percent at term corrected gestational age following preterm birth.
AB  - OBJECTIVE: Compare customized versus population-based growth curves for
      identification of small-for-gestational-age (SGA) and body fat percent (BF%)
      among preterm infants. METHODS: Prospective cohort study of 204 preterm infants
      classified as SGA or appropriate-for-gestational-age (AGA) by population-based
      and customized growth curves. BF% was determined by air-displacement
      plethysmography. Differences between groups were compared using bivariable and
      multivariable linear and logistic regression analyses. RESULTS: Customized curves
      reclassified 30% of the preterm infants as SGA. SGA infants identified by
      customized method only had significantly lower BF% (13.8 +/- 6.0) than the AGA
      (16.2 +/- 6.3, p = 0.02) infants and similar to the SGA infants classified by
      both methods (14.6 +/- 6.7, p = 0.51). Customized growth curves were a
      significant predictor of BF% (p = 0.02), whereas population-based growth curves
      were not a significant independent predictor of BF% (p = 0.50) at term corrected
      gestational age. CONCLUSION: Customized growth potential improves the
      differentiation of SGA infants and low BF% compared with a standard population
      based growth curve among a cohort of preterm infants.

PMID- 21939343
TI  - Cryptococcus gattii: where do we go from here?
AB  - Infections caused by the emerging pathogen Cryptococcus gattii are increasing in
      frequency in North America. During the past decade, interest in the pathogen has
      continued to grow, not only in North America but also in other areas of the world
      where infections have recently been documented. This review synthesizes existing
      data and raises issues that remain to be addressed.

PMID- 21939345
TI  - Influence of doxorubicin on fluconazole susceptibility and efflux pump gene
      expression of Candida dubliniensis.
AB  - The effect of doxorubicin (DOX) on the fluconazole (FLU) susceptibility of C.
      dubliniensis was investigated. Isolates were exposed to DOX and FLU in a
      chequerboard assay and resistance gene expressions were analysed after DOX
      exposure. The susceptibility of the yeast to FLU was decreased in the presence of
      DOX in the chequerboard assay with FIC indices suggesting an antagonistic effect.
      Gene expression analyses showed an overexpression of CdCDR2. Hence, DOX was found
      to have an impact on resistance mechanisms in C. dubliniensis isolates.

PMID- 21939344
TI  - Low genetic diversity of Pneumocystis jirovecii among Cuban population based on
      two-locus mitochondrial typing.
AB  - Genotypes of two different loci of the Pneumocystis jirovecii mitochondrial gene
      were studied in specimens from a total of 75 Pneumocystis pneumonia patients in
      Spain, France and Cuba. A new genotype of the mitochondrial small subunit rRNA
      gene of P. jirovecii (160A/196T) was identified, which was revealed to be the
      most common in these three countries, especially in Cuba where its proportion
      reached 93.8%. Our data imply that the new genotype might be circulating
      worldwide and also suggests that the distribution of P. jirovecii genotypes could
      be narrower in islands such as Cuba.

PMID- 21939346
TI  - Cross-reactivity in the PlateliaTM Aspergillus enzyme immunoassay caused by
      blastomycosis.
AB  - It is well known that cross reactions with other fungal pathogens including
      Histoplasma capsulatum can occur with the use of the PlateliaTM Aspergillus
      galactomannan assay. We report two patients with confirmed blastomycosis whose
      bronchoalveolar lavage (BAL) fluid tested positive for Aspergillus galactomannan
      despite no evidence of aspergillosis.

PMID- 21939347
TI  - In vitro antifungal activity of DNA topoisomerase inhibitors.
AB  - In this paper we report the results of the study of the in vitro effect of eight
      anticancer DNA topoisomerase inhibitors on the growth of Aspergillus fumigatus,
      A. niger, Candida glabrata and Cryptococcus neoformans. Only one compound,
      idarubicin, displayed promising antifungal activity against A. niger, C. glabrata
      and C. neoformans with MIC(50) values varying between 3.6 and 14.2 MUM (1.8-7.1
      MUg/ml). Three other compounds, aclarubicin, doxorubicin and mitoxantrone, showed
      some antifungal activity against C. glabrata and C. neoformans with MIC(50)
      values in the mid micromolar range. The data of this study indicate that selected
      DNA topoisomerase inhibitors are a promising class of compounds for the
      development of new antifungal agents.

PMID- 21939348
TI  - Antimicrobial susceptibility testing of Shiga toxin-producing Escherichia coli
      from various samples by using a spiral gradient endpoint technique.
AB  - Shiga toxin-producing Escherichia coli (STEC) remains a major public health
      concern. Microbial resistance may be due to use of antimicrobial agents (AAs) as
      a growth promoter in food animals or overuse of AAs in humans. The objective of
      the current study was to determine the antimicrobial susceptibility patterns of
      STEC strains isolated from food, veterinary, and clinical sources against 14 AAs
      by using the spiral gradient endpoint method. One hundred ten isolates from three
      sources were characterized. Results of the current study showed that all strains
      were resistant to the folate pathway inhibiting AAs including tylosin tartrate
      (gradient minimum inhibitory concentration [GMIC] ranges from >=180.00 to 256.00
      MUg/mL; end concentration [EC] ranges from >=130.00 to 151.22 MUg/mL; and tail
      end concentration [TEC] >=145.00 MUg/mL). All the strains isolated from three
      sources were susceptible to the fluoroquinolone class of AAs (GMIC ranges from
      <=1.00 to 64.30 MUg/mL; EC ranges from <=3.33 to 72.00 MUg/mL; and TEC ranges
      from <=12.13 to 45.00 MUg/mL). Among the food isolates, less resistance was found
      within the aminoglycoside and amphenicol group (GMIC >=256.00 MUg/mL; EC=161.00
      MUg/mL). Eight strains were resistant to one to three, 44 strains were resistant
      to four to six, and two strains were resistant to seven or more AAs. All the
      clinical isolates (100%) were susceptible to the fluoroquinolones and gentamycin.
      Results also showed that antimicrobial resistance was observed between four and
      six AAs among the isolates. Some veterinary isolates were resistant to five AAs.
      Least AAs resistance was shown by 3.7% of isolates to gentamycin and 7.45% to
      chloramphenicol. This study showed an increasing trend of antimicrobial resistant
      strains of STEC, and we suggest that periodic surveillance of the antimicrobial
      susceptibility may be a useful measure to detect the antimicrobial resistant
      pathogens.

PMID- 21939349
TI  - Phenotypic characterization and prevalence of enterotoxin genes in Staphylococcus
      aureus isolates from outbreaks of illness in Chengdu City.
AB  - Staphylococcus aureus produces a spectrum of enterotoxin that is recognized as
      the main reason for causing staphylococcal food poisoning. The aim of the current
      study was to investigate the phenotypic characteristics and enterotoxin genotypes
      of S. aureus isolated from food poisoning sufferers. On the basis of the
      amplification of 16S rRNA and nuc gene specific to S. aureus assay and the
      phenotype (hemolytic activity, thermal stable nuclease [Tnase] test, and biofilm
      formation), all isolates were identified as S. aureus. To genotypically
      characterize S. aureus isolates, genes encoding staphylococcal enterotoxin (sea,
      seb, sec, sed, see, seg, seh, sei, sej, sek, sem, sen, ser, and seu) were
      investigated by using polymerase chain reaction technique. The results showed
      that the eight isolates of S. aureus had different enterotoxin genotypic
      characteristics, which was the main cause of food poisoning. One isolate
      contained 10 enterotoxin genes, and the other 7 isolates carried 3 or more
      enterotoxin genes. The frequency of the newly identified enterotoxin genes (seg
      seu) was higher than classical genes (sea-see). Overall, multi-gene detection
      rates were 75% (for sek, ser, and seu); 50% (for sea and sem); 37.5% (for sen,
      seg, and sei); and 12.5% (for seb, sec, sed, and sej), respectively. The see and
      seh gene were not detected in any isolates. The current study provided the exact
      distribution of enterotoxin genes in eight S. aureus strains from food poisoning
      sufferers, which indicated that the pathogenicity of the newly identified
      enterotoxin should be highlighted. The need for prevention of food poisoning
      occurrences caused by enterotoxin of S. aureus should be reinforced.

PMID- 21939350
TI  - Herd factors associated with the serological Yersinia prevalence in fattening pig
      herds.
AB  - Recent epidemiological evidence has demonstrated that pork is an important source
      of yersiniosis in humans. Identifying risk factors and potential interventions in
      swine production that may decrease the risk of pork production contamination
      during harvest and processing is an important step before controlling Yersinia
      spp. Therefore, management strategies and production processes that might be
      associated with fattening pigs testing seropositive for pathogenic Yersinia spp.
      were investigated in 80 fattening pig farms. Although >70 farm characteristics
      were included in the risk assessment, there were only a few that seemed to be
      connected with serological prevalence: housing on a fully slatted floor and the
      use of municipal water were observed more often in herds with low serological
      Yersinia prevalence, whereas recurring health problems and a low daily weight
      gain compared with the mean of the herds included in the study were found in
      herds with a high prevalence. Besides, the Yersinia prevalence seemed to be
      inversely proportional to the herds' serological Salmonella status collected in
      accordance with German legislation. Additionally, the development of the
      serological Yersinia status of selected herds was assessed over a period of a
      year to gain knowledge of the dynamics of Yersinia infections in fattening pig
      herds. Three out of four serological negative herds maintained a low level of
      Yersinia prevalence, whereas one herd shifted between negative status and a
      prevalence of 100%. The reason for these considerable fluctuations could not be
      explained, and there was no direct association with the analyzed risk factors.
      Further research should be carried out to prove the given risk factors,
      especially the possible relation to the Salmonella prevalence before implementing
      a combined zoonoses surveillance and control program.

PMID- 21939351
TI  - Synergistic effect of Er:YAG laser irradiation in combination with chlorhexidine
      on the viability of Enterococcus faecalis: an in vitro study.
AB  - OBJECTIVE: This study aimed to examine the potential synergistic effect of laser
      and chlorhexidine (CHX) applications on the growth of Enterococcus faecalis.
      BACKGROUND DATA: CHX has been recommended for root canal irrigation because of
      its antibacterial properties. Er:YAG 2.94??m laser irradiation was shown to be
      beneficial in disinfecting infected root canals. Producing minimal side effects
      is the goal of any clinical procedure. One means of achieving this is via a
      synergistic effect caused by simultaneously introducing two applications with
      reduced dosages, with no compromise on their biological effect. METHODS:
      Bacterial suspensions of E. faecalis supplemented with 0.01?0.0001% v/v CHX
      solutions were lased at energy levels between 300 and 500?mJ. Bacterial growth
      was continuously monitored for 18?h using a GENios apparatus. RESULTS: Laser
      irradiation between 350 and 500?mJ delayed initiation of bacterial growth for
      6?h. A concentration of 0.0001% CHX did not delay bacteria growth. However, a
      combination of 0.0001% CHX and laser irradiation had a synergistic effect on
      bacterial growth. A maximal inhibition period of bacterial growth was observed at
      energy levels of 500?mJ with 0.0001% CHX. CONCLUSIONS: Laser combined with CHX
      has a synergistic effect in killing E. faecalis. A combined regimen of a low
      concentration of CHX with laser irradiation was found to be a potential means of
      inhibiting bacterial growth.

PMID- 21939352
TI  - Nonhormonal treatments for heavy menstrual bleeding.
AB  - BACKGROUND: The purpose of this review is to identify and compare nonhormonal
      medications for the treatment of idiopathic heavy menstrual bleeding (HMB) or
      menorrhagia. METHODS: Clinical trials were identified through a PubMed literature
      search. Titles and abstracts of identified studies were reviewed. Controlled
      clinical trials that evaluated nonhormonal medications in women with HMB in the
      absence of anatomic abnormalities other than small fibroids were selected for
      retrieval. Additional studies were identified from the reference lists of
      selected articles. Selected articles were comprehensively reviewed. RESULTS: All
      medications evaluated reduced menstrual blood loss (MBL); however, mean
      reductions in MBL were greatest with the hemostatic agents, tranexamic acid (TA)
      and epsilon-aminocaproic acid. Several TA studies also included evidence of
      improvement in health-related quality of life (HRQOL). Reductions in MBL were
      generally smaller and less consistent with nonsteroidal anti-inflammatory drug
      (NSAID) treatment. All medications reviewed were well tolerated. CONCLUSIONS:
      Nonhormonal medications used for HMB treatment differ in the extent of MBL
      reduction. TA was notable for consistent MBL reductions and improvement in HRQOL;
      other agents reviewed indicated less reduction in MBL or sufficient data were
      lacking for comparison.

PMID- 21939353
TI  - Single-incision thoracoscopic surgery in children: equivalent results with fewer
      scars when compared with traditional multiple-incision thoracoscopy.
AB  - BACKGROUND: Single-incision pediatric endosurgery is gaining popularity,
      especially for abdominal operations. Several reports in the literature support
      the feasibility of the single-incision approach in pediatric laparoscopy. Here we
      compare our experience with single-incision thoracoscopic surgery (SITS) to
      traditional multiple-incision video-assisted thoracoscopic surgery (VATS) in
      children. METHODS: A chart review of all patients who underwent SITS at our
      institution was performed. The same number of demographically matched VATS case
      controls were selected from a pool of patients operated on during the same time
      period. Operative time, time until chest tube removal, length of stay,
      complications, and any need for further intervention were recorded. Statistical
      analysis was done by Student's t-test using Instat 3. RESULTS: Fourteen SITS
      procedures were performed during the study period. These patients were compared
      with 14 VATS case controls. Both groups were similar with regard to age, weight,
      sex, and procedures performed. The mean operative time in the SITS group was 84
      +/- 43 minutes versus 64 +/- 30 in the VATS group (P=.18). Days until chest tube
      removal was 4 +/- 2.2 in the SITS group and 2.8 +/- 1.4 in the VATS group
      (P=.09). Length of hospital stay was 5.5 +/- 4.4 days in the SITS group versus
      7.2 +/- 8.6 in the VATS group (P=.51). There were no intraoperative complications
      and no procedure conversions in either group. One SITS patient who underwent a
      wedge resection and mechanical pleurodesis for a spontaneous pneumothorax was
      readmitted for a recurrent pneumothorax and required a reoperation. CONCLUSIONS:
      Our experience demonstrates that there are no statistically significant
      differences in operative time, time until chest tube removal, and length of
      hospital stay when comparing SITS to VATS in children. We believe that SITS is an
      equivalent procedure that allows for fewer scars when compared with traditional
      multiple-incision VATS in children.

PMID- 21939354
TI  - Introduction of alvimopan into an enhanced recovery protocol for colectomy offers
      benefit in open but not laparoscopic colectomy.
AB  - INTRODUCTION: Alvimopan coupled with an enhanced recovery protocol (ERP) has been
      shown to reduce length of stay (LOS) after open colectomy, but its role after
      laparoscopy remains unknown. This study evaluated alvimopan with an established
      ERP for laparoscopic (LAP), hand-assisted laparoscopic (HAL), and open colectomy.
      MATERIALS AND METHODS: Consecutive patients who underwent elective colectomy by
      any technique were retrospectively identified. Patients were excluded if they
      developed a major intra-abdominal complication, medical complication, or had a
      complex preoperative evaluation. Patients were stratified into 4 groups based on
      the surgical approach (open/HAL vs. LAP) and the use of alvimopan. All patients
      were managed by using an ERP. The incidence of postoperative ileus (POI) and LOS
      were compared between alvimopan and control groups for each surgical approach.
      RESULTS: There were 282 patients. Demographics were similar across the 4 groups.
      The mean number of alvimopan doses administered was 6.7+/-2.6. For patients in
      the open/HAL group (n=149), the incidence of primary ileus was 9.5% (7/74) and
      16% (12/75) for alvimopan and control patients, respectively (P=.231). A
      significant decrease in LOS was noted with alvimopan (5.6+/-2.5 vs. 6.8+/-3.3
      days, P=.009). For patients after LAP (n=133), there was no significance
      difference in POI with or without alvimopan (3.9% [3/76] vs. 3.5% [2/57],
      P=1.00). There was no difference in LOS (3.9+/-1 vs. 3.7+/-1.4 days, P=.305).
      CONCLUSION: The addition of alvimopan to an established ERP will lead to
      improvement in clinical outcomes in patients after open/HAL colectomy. The
      benefit of alvimopan after LAP remains negligible.

PMID- 21939355
TI  - Cardiaplication: a novel surgical technique for refractory gastroesophageal
      reflux in the pediatric population.
AB  - INTRODUCTION: We encountered 3 patients with severe gastroesophageal reflux
      disease and tubular stomachs precluding fundoplication. Here, we report the use
      of an innovative technique, cardiaplication, as an alternative approach for
      antireflux surgery. METHODS: Three infants with medically refractory
      gastroesophageal reflux disease (GERD) were referred for fundoplication. In each
      case, the patient's anatomy prevented a traditional fundoplication from being
      performed. A cardiaplication was performed by invaginating the cardia of the
      stomach at the angle of His and securing the invaginated tissue with interrupted
      silk suture. The plication tubularized the cardia of the stomach, essentially
      increasing the intra-abdominal portion of the esophagus and altering the angle of
      His. The imbrication also creates a flapper valve over the distal esophagus,
      further limiting potential reflux. The charts for the infants who received
      cardiaplication were reviewed. Radiographic studies and clinical notes for the
      presence of persistent reflux were evaluated. RESULTS: Cardiaplication was
      completed in 3 patients with GERD. All cases were initiated laparoscopically and
      one was converted to an open procedure secondary to dense adhesive disease. Each
      child was initiated on feeds between postoperative day 2 and 3. Two of the 3
      patients were tolerating goal feeds with-in 2 days. The third patient reached
      goal feeds on day 16. Postoperative imaging (upper gastrointestinal series [UGI])
      was obtained in 2 of the 3 patients. At follow-up (13, 7, and 4 months), all 3
      patients are clinically free of symptoms of GERD. Delayed radiographic imaging
      has confirmed that the patients are no longer refluxing. CONCLUSION: Based on
      preliminary findings, cardiaplication appears to be a safe and effective surgical
      technique for the management of severe GERD in infants. We performed
      cardiaplication out of necessity; however, after further testing this may prove
      to be an optimal approach, as it can be performed without disruption of the
      hiatus.

PMID- 21939356
TI  - Pilot study evaluation of standard laparoscopic suturing and a novel parenchymal
      apposition mechanism for minimally invasive renal reconstruction.
AB  - OBJECTIVES: The most technically demanding portion of a laparoscopic partial
      nephrectomy is the renorrhaphy. The purpose of this study was to determine
      whether a parenchymal apposition mechanism (PAM) device would be as effective as
      standard laparoscopic technique (SLT) with respect to efficiency, capability, and
      safety of renal defect closure. MATERIALS AND METHODS: In this pilot study,
      participants were recruited to perform surgical reconstruction of a standardized
      renal parenchymal defect with both SLT and the PAM. The PAM prototype was
      engineered using two salmon egg hooks connected by absorbable suture and placed
      within a V-shaped foam delivery mechanism. After hook placement, tensioning of
      the connecting suture using a Weck clip apposed the defect edges. Each
      participant performed a single closure with SLT and with the PAM device of a
      standardized defect in ex vivo porcine kidneys. Closure time, tissue
      trauma/damage during closure, and the intraparenchymal pressure were recorded.
      RESULTS: A total of 13 subjects, 7 medical students, 3 residents, 2 fellows, and
      1 attending were enrolled. There was no statistical difference between the two
      methods of closure in average time for closure. In a subgroup analysis of
      subjects who had performed laparoscopic reconstructive procedures as the primary
      surgeon, SLT was significantly faster than PAM (P=.036). Mean pressures achieved
      in attempted closure using SLT and PAM were not significantly different (0.38 N
      for both groups; P=.99). The mean parenchymal trauma rating was not significantly
      different between the groups; however, the upper limit of the range of trauma
      ratings was greater in the standard closures. CONCLUSION: This pilot study
      demonstrated the feasibility of PAM use in an ex vivo porcine kidney model.
      Additional testing and continued design modifications are necessary to explore
      its use in laparoscopic reconstruction of the kidney and other organs.

PMID- 21939357
TI  - A rare anomaly of testicular descend: transverse testicular ectopia and review of
      the literature.
AB  - Crossed ectopia or transverse testicular ectopia (TTE) is an extremely rare
      anomaly of testicular descent in which both gonads migrate along the same
      inguinal canal to the hemiscrotum. Fewer than 100 cases have been reported in the
      literature. Most cases of TTE involve a concomitant inguinal hernia on the
      contralateral side. A radiological evaluation and laparoscopy are essential for
      appropriate diagnosis and treatment. Although a correct diagnosis is not
      preoperatively made in most cases, we present a 15-year-old boy in whom TTE was
      diagnosed by magnetic resonance imaging. A laparoscopic evaluation and treatment
      (orchiectomy) was uneventfully performed.

PMID- 21939358
TI  - Comparison of I-131 radioimmunotherapy tumor dosimetry: unit density sphere model
      versus patient-specific Monte Carlo calculations.
AB  - High computational requirements restrict the use of Monte Carlo algorithms for
      dose estimation in a clinical setting, despite the fact that they are considered
      more accurate than traditional methods. The goal of this study was to compare
      mean tumor absorbed dose estimates using the unit density sphere model
      incorporated in OLINDA with previously reported dose estimates from Monte Carlo
      simulations using the dose planning method (DPMMC) particle transport algorithm.
      The dataset (57 tumors, 19 lymphoma patients who underwent SPECT/CT imaging
      during I-131 radioimmunotherapy) included tumors of varying size, shape, and
      contrast. OLINDA calculations were first carried out using the baseline tumor
      volume and residence time from SPECT/CT imaging during 6 days post-tracer and 8
      days post-therapy. Next, the OLINDA calculation was split over multiple time
      periods and summed to get the total dose, which accounted for the changes in
      tumor size. Results from the second calculation were compared with results
      determined by coupling SPECT/CT images with DPM Monte Carlo algorithms. Results
      from the OLINDA calculation accounting for changes in tumor size were almost
      always higher (median 22%, range -1%-68%) than the results from OLINDA using the
      baseline tumor volume because of tumor shrinkage. There was good agreement
      (median -5%, range -13%-2%) between the OLINDA results and the self-dose
      component from Monte Carlo calculations, indicating that tumor shape effects are
      a minor source of error when using the sphere model. However, because the sphere
      model ignores cross-irradiation, the OLINDA calculation significantly
      underestimated (median 14%, range 2%-31%) the total tumor absorbed dose compared
      with Monte Carlo. These results show that when the quantity of interest is the
      mean tumor absorbed dose, the unit density sphere model is a practical
      alternative to Monte Carlo for some applications. For applications requiring
      higher accuracy, computer-intensive Monte Carlo calculation is needed.

PMID- 21939359
TI  - Eugenol enhances the chemotherapeutic potential of gemcitabine and induces
      anticarcinogenic and anti-inflammatory activity in human cervical cancer cells.
AB  - Administration of natural or synthetic agents to inhibit, delay, block, or
      reverse the initiation and promotional events associated with carcinogenesis
      opens a new avenue for cancer prevention and treatment to reduce cancer morbidity
      and mortality. Eugenol, a potential chemopreventive agent, is a component of
      clove and several other spices such as basil, cinnamon, and bay leaves. A number
      of reports have shown that eugenol possesses antiseptic, analgesic,
      antibacterial, and anticancer properties. The present study was undertaken to
      evaluate the chemopreventive potential of eugenol alone and in combination with a
      chemotherapeutic agent such as gemcitabine. Eugenol showed dose-dependent
      selective cytotoxicity toward HeLa cells in comparison to normal cells, pointing
      to its safe cytotoxicity profile. A combination of eugenol and gemcitabine
      induced growth inhibition and apoptosis at lower concentrations, compared with
      the individual drugs. The analysis of the data using a combination index showed
      combination index values of <1 indicating strong synergistic interaction. The
      combination thus may enhance the efficacy of gemcitabine at lower doses and
      minimize the toxicity on normal cells. In addition, the expression analysis of
      genes involved in apoptosis and inflammation revealed significant downregulation
      of Bcl-2, COX-2, and IL-1beta on treatment with eugenol. Thus, the results
      suggest that eugenol exerts its anticancer activities via apoptosis induction and
      anti-inflammatory properties and also provide the first evidence demonstrating
      synergism between eugenol and gemcitabine, which may enhance the therapeutic
      index of prevention and/or treatment of cervical cancer.

PMID- 21939360
TI  - Ameliorative influence of Urtica dioica L against cisplatin-induced toxicity in
      mice bearing Ehrlich ascites carcinoma.
AB  - Cisplatin (CP) is a widely used cytotoxic agent against cancer, and high doses of
      CP have been known to cause nephrotoxicity and hepatotoxicity. Some reports claim
      that antioxidants can reduce CP-induced toxicity. This study investigated the
      hepatoprotective, nephroprotective, and antioxidant activity of Urtica dioica L
      methanolic extract (UDME) against CP toxicity in Erhlich ascites tumor (EAT)
      bearing mice. Levels of serum hepatic enzymes, renal function markers, and
      oxidant/antioxidant parameters of liver tissue were measured. Mice were
      inoculated with EAT on day 0 and treated with nothing else for 24 hours. After a
      single dose of CP administration on day 1, the extract was given at the doses of
      50, 100, 200, and 400 mg/kg body weight daily during 6 days. Almost all doses of
      UDME performed a significant (P < 0.05) preventive role against CP toxicity by
      decreasing aspartate aminotransferase, alanine aminotransferase, lactate
      dehydrogenase, blood urea nitrogen, creatinine, lipid peroxidation, protein
      oxidation levels, and myeloperoxidase activity, as well as increasing reduced
      glutathione content, superoxide dismutase, catalase, glutathione S-transferase,
      and glutathione peroxidase activities. This suggests that UDME has a protective
      capacity and antioxidant activity against CP toxicity in EAT-bearing mice,
      probably by promoting antioxidative defense systems.

PMID- 21939361
TI  - A comparison of BGM and LLC-PK1 cells for the evaluation of nephrotoxicity.
AB  - Nephrotoxicity is one of the most frequent effects observed after the use of
      medicine. Such situations have been tardily discovered because of existing
      methods to determine toxicity. The validation of sensitive, alternative methods
      for the early identification of toxic effects is as important as restrictions on
      the use of animals. In this light, the present study evaluated the effects of
      gentamicin on BGM and LLC-PK1 cells, using MTT and Neutral Red (NR). Although the
      LLC-PK1 cell line is used for toxicological studies, the BGM cell line is
      relatively new for this purpose. MTT (BGM: EC(50) = 6.29 mM; LLC-PK1: EC(50) =
      8.01 mM) was found to be more sensitive than NR (EC(50) was greater than 10 mM
      for both cells). By using MTT, both cells demonstrated the involvement of
      mitochondria in a manner that was dose dependent, with an apoptotic process
      occurring at the concentrations of 1 and 3 mM and necrosis at concentrations
      above 4 mM. It could, therefore, be concluded that 1) BGM appears to be useful in
      the study of the mechanism of nephrotoxicity caused by gentamicin and 2) because
      of its sensitivity to MTT, in addition to its ease of manipulation, it is
      believed that the BGM cell line can also be used as an alternative method to
      evaluate nephrotoxicity.

PMID- 21939362
TI  - The mycotoxin, patulin, increases the expression of PXR and AhR and their target
      cytochrome P450s in primary cultured human hepatocytes.
AB  - The mycotoxin, patulin (PAT), which is frequently found in apples, grapes,
      oranges, pear, peaches, and in apple juices, has previously been shown to be
      cytotoxic, genotoxic, and mutagenic. In this study, we have investigated the
      effect of PAT on mRNA level of pregnane X receptor (PXR), constitutive androstane
      receptor (CAR), aryl hydrocarbon receptor (AhR), and their corresponding target
      cytochrome P450s. Using primary cultures of adult human hepatocytes, we evaluated
      PAT cytotoxicity on hepatocytes after 24 hours of treatment. Real time reverse
      transcriptase polymerase chain reaction procedure was employed to determine the
      effect of PAT on receptors (PXR, CAR, and AhR) and cytochrome (CYP3A4, 2B6, 3A5,
      2C9, 1A1, and 1A2) genes. Our results showed that PAT reduced hepatocyte
      viability. At a noncytotoxic range of PAT concentrations, PAT induced an
      upregulation of the PXR gene in the three treated hepatocytes cultures, whereas
      CAR was overexpressed in only 1 treated liver. PXR gene induction was accompanied
      by the enhancement of CYP2B6, 3A5, 2C9, and 3A4 expression. PAT was also found to
      induce an overexpression of AhR and CYP1A1 and CYP1A2 mRNA expression. These
      findings suggested that PAT may activate PXR and/or CAR and AhR. However, further
      investigations are needed to confirm nuclear receptor activation by PAT and to
      elucidate the molecular mechanism of PAT action.

PMID- 21939363
TI  - Preventive effect of phytoglycoprotein (38 kDa) on expression of alpha
      fetoprotein and matrix metalloproteinase-9 in diethylnitrosamine-treated ICR
      mice.
AB  - Metastasis is one of the major causes of cancer-associated mortality. Aberrant
      expression of matrix metalloproteinase-9 (MMP-9) has been implicated in the
      metastasis of various cancer cells. The aim of this study was to investigate the
      inhibitory effect of a glycoprotein (38 kDa) isolated from Styrax japonica
      Siebold et al Zuccarini (SJSZ) on metastasis of hepatocellular carcinoma (HCC) in
      diethylnitrosamine (DEN)-treated imprinting control region (ICR) mice. To study
      the chemopreventive effect of SJSZ glycoprotein on the metastasis of HCC, ICR
      mice were injected intraperitoneally with DEN (75 mg/kg) for 11 weeks.
      Subsequently, we evaluated nitric oxide (NO), alpha-fetoprotein (AFP), activator
      protein (AP)-1, cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS),
      matrix metalloproteinase (MMP)-9, and interleukin (IL)-6 using biochemical
      reaction, immunoblot analysis, and reverse-transcription polymerase chain
      reaction. Here, the results showed that SJSZ glycoprotein (10 mg/kg body weight)
      reduced the production of NO in DEN (75 mg/kg)-treated ICR mice. Also, it
      suppressed the activity of AFP, AP-1 (c-Jun and c-Fos), COX-2, iNOS, and MMP-9.
      Taken together, SJSZ glycoprotein inhibits the activity of MMP-9 as a metastasis
      factor.

PMID- 21939364
TI  - Development of a method of clozapine dosage by selective electrode to the
      iodides.
AB  - Clozapine (Leponex((r))), the main neuroleptic indicated in the treatment of
      resistant schizophrenia, requires therapeutic monitoring because of its side
      effects and the individual variability in metabolism. In addition, several cases
      of intoxication by this drug were described in the literature. In this work, we
      studied the indirect dosage of clozapine by selective electrode to the iodides
      for the optimization of an analytical protocol allowing therapeutic monitoring
      and the diagnosis of intoxication and/or overdose. Our results showed that the
      developed method is linear between 0.05 and 12.5 ug/mL (r = 0.980), with a limit
      of detection of 0.645.10(-3) ug/mL. It presents good precision (coefficient of
      variation less than 4%) and accuracy (coefficient less than 10%) for all the
      studied concentrations. With a domain of linearity covering a wide margin of
      concentrations, this method can be applicable to the dosage of clozapine in
      tablets and in different biological matrices, such as plasma, urines, and
      postmortem samples.

PMID- 21939366
TI  - The reminiscence bump in the temporal distribution of the best football players
      of all time: Pele, Cruijff or Maradona?
AB  - The reminiscence bump is the tendency to recall more autobiographical memories
      from adolescence and early adulthood than from adjacent lifetime periods. In this
      online study, the robustness of the reminiscence bump was examined by looking at
      participants' judgements about the quality of football players. Dutch
      participants (N = 619) were asked who they thought the five best players of all
      time were. The participants could select the names from a list or enter the names
      when their favourite players were not on the list. Johan Cruijff, Pele, and Diego
      Maradona were the three most often mentioned players. Participants frequently
      named football players who reached the midpoint of their career when the
      participants were adolescents (mode = 17). The results indicate that the
      reminiscence bump can also be identified outside the autobiographical memory
      domain.

PMID- 21939365
TI  - Determination of parathion, aldicarb, and thiobencarb in tap water and bottled
      mineral water in Mashhad, Iran.
AB  - Water is a necessity for life. Currently, because of different contaminations in
      tap water, most people prefer using bottled mineral waters. Pesticides (e.g.,
      organophophorous, carbamates, etc.) are among the most dangerous chemicals that
      may be found in drinking waters, which can cause long- and short-term
      complications. Because all people consume at least 2 L of water per day, water
      quality monitoring is vital. In this study, we determined the concentration of
      three pesticides (aldicarb, parathion, and thiobencarb) in 13 tap-water samples
      collected from 13 different urban areas and 10 samples of bottled mineral water
      in Mashhad, a major city in northeast Iran. Samples were analyzed by gas
      chromatography coupled with a pulsed flame photometric detector after solid-phase
      extraction. Results showed that 2 of 13 tap-water samples and 2 of 10 bottled
      mineral water trademarks were contaminated either by parathion or by thiobencarb
      or both, with concentrations ranging between 0.6 and 0.8 ppb. According to the
      defined guideline values, determined concentrations of pesticides are below the
      permissible World Health Organization level for these toxic agents, and it is
      considered that drinking these tap waters and bottled mineral waters are safe for
      human consumption.

PMID- 21939367
TI  - Effects of visual cue and response assignment on spatial stimulus coding in
      stimulus-response compatibility.
AB  - Tlauka and McKenna ( 2000 ) reported a reversal of the traditional stimulus
      response compatibility (SRC) effect (faster responding to a stimulus presented on
      the same side than to one on the opposite side) when the stimulus appearing on
      one side of a display is a member of a superordinate unit that is largely on the
      opposite side. We investigated the effects of a visual cue that explicitly shows
      a superordinate unit, and of assignment of multiple stimuli within each
      superordinate unit to one response, on the SRC effect based on superordinate unit
      position. Three experiments revealed that stimulus-response assignment is
      critical, while the visual cue plays a minor role, in eliciting the SRC effect
      based on the superordinate unit position. Findings suggest bidirectional
      interaction between perception and action and simultaneous spatial stimulus
      coding according to multiple frames of reference, with contribution of each
      coding to the SRC effect flexibly varying with task situations.

PMID- 21939368
TI  - Consensus collaboration enhances group and individual recall accuracy.
AB  - We often remember in groups, yet research on collaborative recall finds
      "collaborative inhibition": Recalling with others has costs compared to recalling
      alone. In related paradigms, remembering with others introduces errors into
      recall. We compared costs and benefits of two collaboration procedures--turn
      taking and consensus. First, 135 individuals learned a word list and recalled it
      alone (Recall 1). Then, 45 participants in three-member groups took turns to
      recall, 45 participants in three-member groups reached a consensus, and 45
      participants recalled alone but were analysed as three-member nominal groups
      (Recall 2). Finally, all participants recalled alone (Recall 3). Both turn-taking
      and consensus groups demonstrated the usual pattern of costs during collaboration
      and benefits after collaboration in terms of recall completeness. However,
      consensus groups, and not turn-taking groups, demonstrated clear benefits in
      terms of recall accuracy, both during and after collaboration. Consensus groups
      engaged in beneficial group source-monitoring processes. Our findings challenge
      assumptions about the negative consequences of social remembering.

PMID- 21939369
TI  - Perceived acceptability of home-based couples voluntary HIV counseling and
      testing in Northern Tanzania.
AB  - It is estimated that 5.6% of the Tanzanian population ages 15-49 are infected
      with HIV, but only 30% of adults have ever had an HIV test. Couples' testing has
      proven to increase testing coverage and introduce HIV prevention, but barriers
      include access to testing services and unequal gender dynamics in relationships.
      Innovative approaches are needed to address barriers to couple's testing and
      increase uptake of HIV testing. Using qualitative data collection methods, a
      formative study was conducted to assess the acceptability of a home-based couples
      counseling and testing (HBCCT) approach. Eligible study participants included
      married men and women, HIV-infected individuals, health care and home-based care
      providers, voluntary counseling and testing counselors, and community leaders. A
      total of 91 individuals participated in focus group discussions (FGDs) and in
      depth interviews conducted between September 2009 and January 2010 in rural
      settings in Northern Tanzania. An HBCCT intervention appears to be broadly
      acceptable among participants. Benefits of HBCCT were identified in terms of
      access, confidentiality, and strengthening the relationship. Fears of negative
      consequences from knowing one's HIV status, including stigma, blame, physical
      abuse, or divorce, remain a concern and a potential barrier to the successful
      provision of the intervention. Lessons for implementation highlighted the
      importance of appointments for home visits, building relationships of confidence
      and trust between counselors and clients, and assessing and responding to a
      couple's readiness to undergo HIV testing. HBCCT should addresses HIV stigma,
      emphasize confidentiality, and improve communication skills for disclosure and
      decision-making among couples.

PMID- 21939370
TI  - Comparative larvicidal activity of different species of Ocimum against Culex
      quinquefasciatus.
AB  - Ocimum is a genus of aromatic herbs, undershurbs or shrubs distributed in the
      tropical and warm temperate regions of the world. Larvicidal activity of
      essential oils and different extracts of O. sanctum, O. basilicum and O.
      gratissimum were compared on laboratory reared and field collected larvae of
      Culex quinquefasciatus. Thin layer chromatographic analysis revealed that all the
      three species have similar components and results showed the presence of steroids
      and triterpenoids. The larvicidal activity was determined in terms of LD50 value
      on late third or early fourth instar larvae for a period of 24 h. A comparison of
      LD50 value has shown that O. basilicum is more active than the other two species.
      The LD50 value of O. basilicum and O. sanctum oil were 39.31 and 40.02 on
      laboratory reared larvae and 129.53 and 139.49 on field collected larvae.
      Laboratory reared larvae were more sensitive than field collected larvae.

PMID- 21939371
TI  - Chemical composition of the essential oil from basil (Ocimum basilicum Linn.) and
      its in vitro cytotoxicity against HeLa and HEp-2 human cancer cell lines and NIH
      3T3 mouse embryonic fibroblasts.
AB  - This study examines the chemical composition and in vitro anticancer activity of
      the essential oil from Ocimum basilicum Linn. (Lamiaceae), cultivated in the
      Western Ghats of South India. The chemical compositions of basil fresh leaves
      were identified by GC-MS: 11 components were identified. The major constituents
      were found to be methyl cinnamate (70.1%), linalool (17.5%), beta-elemene (2.6%)
      and camphor (1.52%). The results revealed that this plant may belong to the
      methyl cinnamate and linalool chemotype. A methyl thiazol tetrazolium assay was
      used for in vitro cytotoxicity screening against the human cervical cancer cell
      line (HeLa), human laryngeal epithelial carcinoma cell line (HEp-2) and NIH 3T3
      mouse embryonic fibroblasts. The IC(50) values obtained were 90.5 and 96.3 ug mL(
      1), respectively, and the results revealed that basil oil has potent
      cytotoxicity.

PMID- 21939372
TI  - Gene cloning, structural gene and promoter identification, and active assay of
      the phosphatidylcholine synthase of Pseudomonas sp. strain 593.
AB  - Pseudomonas sp. strain 593, a soil bacterium, is able to use exogenous choline to
      synthesize phosphatidylcholine via phosphatidylcholine synthase (Pcs). A 2020 bp
      DNA fragment that hybridized to a Pcs probe was cloned. This fragment contained a
      large open reading frame (ORF) with two potential ATG start sites that would
      encode for 293 and 231 amino acid proteins. Fragments containing the two ORFs
      encoded Pcs when they were inserted into the expression vector pET23a and
      expressed under the control of the T7 promoter in Escherichia coli BL21(DE3)
      pLysS. However, when the two ORFs were inserted into the cloning vector pMD18-T
      and expressed without control of the plasmid promoter in E. coli DH5alpha, only
      the larger clone exhibited Pcs activity. This suggested that the larger fragment
      contained a native promoter driving expression of the smaller ORF. A promoter
      activity assay, in which DNA fragments were inserted into the promoter-probe
      plasmid pCB182 and beta-galactosidase activity of E. coli transformants was
      tested, demonstrated that a promoter is indeed present in the DNA region. All
      results together indicate that the 696 bp ORF, not the larger 897 bp ORF, encodes
      the Pcs in Pseudomonas sp. strain 593 and carries a promoter in front of its 5'
      terminus.

PMID- 21939373
TI  - Vulnerability of conditional NCAM-deficient mice to develop stress-induced
      behavioral alterations.
AB  - Previous studies in rodents showed that chronic stress induces structural and
      functional alterations in several brain regions, including shrinkage of the
      hippocampus and the prefrontal cortex, which are accompanied by cognitive and
      emotional disturbances. Reduced expression of the neural cell adhesion molecule
      (NCAM) following chronic stress has been proposed to be crucially involved in
      neuronal retraction and behavioral alterations. Since NCAM gene polymorphisms and
      altered expression of alternatively spliced NCAM isoforms have been associated
      with bipolar depression and schizophrenia in humans, we hypothesized that reduced
      expression of NCAM renders individuals more vulnerable to the deleterious effects
      of stress on behavior. Here, we specifically questioned whether mice in which the
      NCAM gene is inactivated in the forebrain by cre-recombinase under the control of
      the calcium-calmodulin-dependent kinase II promoter (conditional NCAM-deficient
      mice), display increased vulnerability to stress. We assessed the evolving of
      depressive-like behaviors and spatial learning and memory impairments following a
      subchronic stress protocol (2 weeks) that does not result in behavioral
      dysfunction, nor in altered NCAM expression, in wild-type mice. Indeed, while no
      behavioral alterations were detected in wild-type littermates after subchronic
      stress, conditional NCAM-deficient mice showed increased immobility in the tail
      suspension test and deficits in reversal spatial learning in the water maze.
      These findings indicate that diminished NCAM expression might be a critical
      vulnerability factor for the development of behavioral alterations by stress and
      further support a functional involvement of NCAM in stress-induced cognitive and
      emotional disturbances.

PMID- 21939374
TI  - Analysis of the strengths, weaknesses, opportunities and threats of the network
      form of organization of traumatic brain injury service delivery systems.
AB  - Networks are an increasingly popular way to deal with the lack of integration of
      traumatic brain injury (TBI) care. Knowledge of the stakes of the network form of
      organization is critical in deciding whether or not to implement a TBI network to
      improve the continuity of TBI care. GOALS OF THE STUDY: To report the strengths,
      weaknesses, opportunities, and threats of a TBI network and to consider these
      elements in a discussion about whether networks are a suitable solution to
      fragmented TBI care. METHODS: In-depth interviews with 12 representatives of
      network organization members. Interviews were qualitatively analyzed using the
      EGIPSS model of performance. RESULTS: The majority of elements reported were
      related to the network's adaptation to its environment and more precisely to its
      capacity to acquire resources. The issue of value maintenance also received
      considerable attention from participants. DISCUSSION: The network form of
      organization seems particularly sensitive to environmental issues, such as
      resource acquisition and legitimacy. The authors suggest that the network form of
      organization is a suitable way to increase the continuity of TBI care if the
      following criteria are met: (1) expectations toward network effectiveness to
      increase continuity of care are moderate and realistic; (2) sufficient resources
      are devoted to the design, implementation, and maintenance of the network; (3) a
      network's existence and actions are deemed legitimate by community and
      organization member partners; and (4) there is a good collaborative climate
      between the organizations.

PMID- 21939375
TI  - Estimating core temperature with external devices after exertional heat stress in
      thermal protective clothing.
AB  - BACKGROUND: Temperature measurement is important for emergency medical services
      (EMS) providers when identifying and treating heat illness or infection. Direct
      measures of body core temperature (T(c)) are often expensive (ingestible
      capsules) or impractical (rectal probes) in the field. Multiple devices for
      estimating T(c) have been adopted by EMS providers, with little understanding of
      the agreement between these devices and T(c). OBJECTIVE: To examine the agreement
      between the results of five external thermometers and T(c) after subjects
      experienced physical exertion while wearing protective clothing. METHODS: Fifty
      firefighters completed treadmill walking in thermal protective clothing in a hot
      environment. Measurements of core, temporal, tympanic, forehead, and skin
      temperatures were obtained during a 20-minute recovery period simulating
      emergency incident rehabilitation. RESULTS: The mean bias of external
      thermometers ranged from -1.31 degrees C to -3.28 degrees C when compared with
      T(c) and exceeded the predetermined clinical cutoff of +/-0.5 degrees C from
      T(c). The 95% limits of agreement ranged from 2.75 degrees C to 5.00 degrees C.
      CONCLUSIONS: External measuring devices failed to accurately predict T(c) in
      hyperthermic individuals following exertion. Confidence intervals around the bias
      were too large to allow for reasonable estimation of T(c). EMS providers should
      exercise caution when using any of these temperature estimation techniques.

PMID- 21939376
TI  - Sequencing of CJIE1 prophages from  Campylobacter jejuni  isolates reveals the
      presence of inserted and (or) deleted genes.
AB  - Bacteriophages capable of integrating into host bacterial genomes as prophages
      affect the biology and virulence of their bacterial hosts. Previously, partial
      sequencing of 12 prophages similar to CJIE1 from Campylobacter jejuni RM1221 did
      not show the presence of inserted nonphage genes. Therefore, four of these
      prophages were sequenced completely, and indels were found in at least two
      different regions of the prophage genome. Putative proteins from one indel
      appeared to be members of two new families of proteins, with proteins within each
      family related to each other by a common domain. Further heterogeneity was found
      adjacent to the CJE0270 homolog, creating difficulty locating the end of the
      prophage on this side and in determining the composition of the core prophage.
      These prophages appear to comprise a family that has heterogeneity in gene
      content resulting from insertion or deletion of additional genes at three
      locations in their genomes. In addition, members of the CJIE1 phage family may
      differ somewhat in their biology from phage Mu. Further investigations of these
      Campylobacter prophages can be expected to provide interesting insights into the
      biology of the phages themselves and into the role of these phages in the biology
      of their hosts.

PMID- 21939378
TI  - Interactions of the human pathogenic Brucella species with their hosts.
AB  - Brucellosis is a zoonotic infection caused primarily by the bacterial pathogens
      Brucella melitensis and B. abortus. It is acquired by consumption of
      unpasteurized dairy products or by contact with infected animals. Globally, it is
      one of the most widespread zoonoses, with 500,000 new cases reported each year.
      In endemic areas, Brucella infections represent a serious public health problem
      that results in significant morbidity and economic losses. An important feature
      of the disease is persistent bacterial colonization of the reticuloendothelial
      system. In this review we discuss recent insights into mechanisms of
      intracellular survival and immune evasion that contribute to systemic persistence
      by the pathogenic Brucella species.

PMID- 21939379
TI  - School time.

PMID- 21939377
TI  - Motility and chemotaxis in Campylobacter and Helicobacter .
AB  - Flagellar motility of Campylobacter jejuni and Helicobacter pylori influences
      host colonization by promoting migration through viscous milieus such as
      gastrointestinal mucus. This review explores mechanisms C. jejuni and H. pylori
      employ to control flagellar biosynthesis and chemotactic responses. These
      microbes tightly control the activities of sigma(54) and sigma(28) to mediate
      ordered flagellar gene expression. In addition to phase-variable and
      posttranslational mechanisms, flagellar biosynthesis is regulated spatially and
      numerically so that only a certain number of organelles are placed at polar
      sites. To mediate chemotaxis, C. jejuni and H. pylori combine basic chemotaxis
      signal transduction components with several accessory proteins. H. pylori is
      unusual in that it lacks a methylation-based adaptation system and produces
      multiple CheV coupling proteins. Chemoreceptors in these bacteria contain
      nonconserved ligand binding domains, with several chemoreceptors matched to
      environmental signals. Together, these mechanisms allow for swimming motility
      that is essential for colonization.

PMID- 21939380
TI  - Effect of e-health on medical expenditures of outpatients with lifestyle-related
      diseases.
AB  - We analyzed the effect of e-health on medical expenditures in Nishi-aizu Town,
      Fukushima Prefecture, Japan, using panel data of medical expenditures for about
      400 residents from 2002 to 2006. The Nishi-aizu Town system was introduced in
      1994 and is still successfully operating as one of the longest running
      implementations of e-health in Japan. The town office maintains a register of
      receipts for medical expenditures paid by the National Health Insurance system
      and provides data on e-health users, allowing users and nonusers of e-health and
      their respective costs to be distinguished. Here, we focus on patients with
      lifestyle-related diseases such as high blood pressure, diabetes, stroke, heart
      failure, etc. This article postulates that e-health reduces medical expenditures
      via two mechanisms, decreasing travel expenses and preventing symptoms from
      worsening. The former implies that e-health monitoring allows patients at home to
      visit medical institutions less frequently, and the latter that the symptoms
      experienced by e-health users are less severe than those experienced by nonusers.
      We termed these the travel cost effect and opportunity cost effect, respectively.
      Chronic conditions tend not to occur singly, and many patients have more than
      one; for example, patients with high blood pressure or diabetes also likely have
      heart disease at the same time. This multiplicity of conditions hampers cost
      analysis. Among methodological issues, a number of recent empirical health
      analyses have focused on the endogenous problem of explanatory variables. Here,
      we solved this problem using the generalized method moments (GMM) system, which
      allows treatment of not only the endogenous problem of explanatory variables but
      also the dynamic relationship among variables, which arise due to the chronic
      time-lagged effect of lifestyle-related diseases on patients. We also examined a
      second important methodological problem related to reverse correlation between
      the medical expenditures of an outpatient and e-health and took sampling biases
      into consideration. We concluded that this control of endogeneity through system
      GMM confirms that the relationship between the medical expenditures of an
      outpatient and e-health shows causation rather than simple correlation and that e
      health use, duration of e-health use, and frequency of e-health use can reduce
      outpatient medical expenditures for lifestyle-related diseases.

PMID- 21939381
TI  - Telepsychiatry "coverage" to a rural inpatient psychiatric unit.
AB  - OBJECTIVE: Rural psychiatrists responsible for inpatient psychiatry units in
      general hospitals often have trouble getting coverage for training, vacations,
      and periods of illness. This article describes telepsychiatry "coverage" to a
      rural general hospital psychiatric unit for 1 week. MATERIALS AND METHODS: All
      adult patients meeting criteria for inpatient mental health treatment in the
      emergency room were offered admission to the general hospital after obtaining
      informed consent regarding the use of inpatient telepsychiatry. The number of
      patients on the inpatient psychiatric unit ranged from three to nine, with an
      average daily census of seven. All psychiatric care was provided via video
      teleconferencing (VTC) at a bandwidth of 512 kilobits per second using Internet
      Protocol. RESULTS: Patients with psychosis reported more difficulty hearing the
      doctor than patients without psychosis and incorporated VTC into delusions in a
      congruent manner. Patients rated development of rapport and effectiveness of
      treatment higher than staff ratings. Two staff thought telepsychiatry was either
      not effective for acutely psychotic patients or more effective with higher
      functioning patients. CONCLUSIONS: Short-term coverage of rural inpatient
      psychiatric units for purposes of vacation, training, and illness is possible
      using telepsychiatry. Psychiatrist's efficiency and consistency are enhanced with
      instantaneous connections possible from hospital, office, or home. Significant
      increases in staff workload will occur without remote access to electronic
      medical records, electronic physician ordering, and an adequate physical layout
      of the inpatient psychiatric unit. Adequate educational preparation of unit staff
      regarding telepsychiatry and a staff process group during implementation is
      recommended.

PMID- 21939382
TI  - Web-based training in early autism screening: results from a pilot study.
AB  - BACKGROUND: Lack of familiarity with early signs of autism by community service
      providers has resulted in significant delays in children receiving early
      intervention services necessary to improve long-term outcomes. The Screening Tool
      for Autism in Toddlers and Young Children (STAT) was specifically developed to
      identify early behavioral features of autism. Although STAT training has been
      available for years, access is limited because of few STAT trainers and
      geographic concerns. This study evaluated the efficacy and acceptability of Web
      based training of the STAT as a means of increasing accessibility to this
      training. MATERIALS AND METHODS: Thirty professionals from three geographic areas
      participated. Roughly 1 of 3 had little or no training on autism assessment. The
      tutorial contains a general overview, administration and scoring conventions, and
      item-specific content and concepts. Participants completed a pretest and then
      completed the STAT tutorial at their own pace, followed by a post-test and a user
      satisfaction questionnaire. RESULTS: Mean scores on STAT concepts significantly
      improved after taking the tutorial (p<0.001). At pretest, only 1 person (3%)
      obtained correct scores on at least 80% of the items (a priori cutoff for a
      "pass"), compared with 22 (73%) at post-test (p<0.001). The majority of trainees
      enjoyed taking the tutorial, thought it was well organized, relevant,
      interesting, and useful, and felt it was easy to understand and operate.
      DISCUSSION: Results support Web-based training as a promising method for
      promoting early identification of autism and may help overcome problems
      associated with the critical shortage of autism-screening professionals.

PMID- 21939383
TI  - Pharyngo-cutaneous fistula: an old problem revisited.
AB  - CONCLUSION: Pharyngo-cutaneous fistula is the most common complication after
      total laryngectomy (TL), with many factors linked to its emergence. However, it
      has rarely been associated with the type of pharyngeal suture. We conclude that
      the technique of surgical closure of the pharynx and care in the tightness of the
      suture seem to be fundamental factors for pharyngo-cutaneous fistula development.
      OBJECTIVE: The aim of present work was to determine whether the type of
      pharyngeal suture can be considered as a major risk factor for developing a
      pharyngo-cutaneous fistula following TL. METHODS: We carried out a series of 157
      consecutive TLs. In the first 90 procedures, we performed a pharyngeal closure
      technique with T-shaped interrupted stitches reinforced with constrictors. In the
      other 67 cases, a doubled continuous suture technique with reinforcement with the
      cutaneous flap was developed. RESULTS: In all, 25.5% of the cases sutured with
      the interrupted stitches developed a fistula while only 2.9% of the patients that
      underwent continuous suture developed a fistula.

PMID- 21939387
TI  - Systemic redox regulation of cellular information processing.
AB  - Receptor-mediated signaling leads to transient changes in redox state, resulting
      in reversible oxidation of protein cysteine thiols. Numerous signaling proteins
      have been identified as being redox sensitive; however, to date, most
      investigations have focused on the ramifications of isolated protein
      modifications on cellular phenotypes. We propose that reversible thiol oxidation
      of proteins in a signaling network and their systemic interactions introduce
      features in the dynamics and control of cellular responses that are unique
      compared with isolated oxidative protein modifications. Simulations of dynamic
      redox regulation in different cellular contexts reveal feasible regulatory
      features for future experimental investigation. We suggest that location within a
      network, compartmentalization, and the degree of connectivity between redox
      proteins can dramatically modulate cellular information processing.

PMID- 21939388
TI  - Mycobacterium tuberculosis vitamin K epoxide reductase homologue supports vitamin
      K-dependent carboxylation in mammalian cells.
AB  - AIMS: Vitamin K epoxide reductase complex, subunit 1 (VKORC1) is a critical
      participant in the production of active forms of reduced vitamin K and is
      required for modification of vitamin K-dependent proteins. Homologues of VKORC1
      (VKORH) exist throughout evolution, but in bacteria they appear to function in
      oxidative protein folding as well as quinone reduction. In the current study we
      explore two questions: Do VKORHs function in the mammalian vitamin K cycle? Is
      the pair of loop cysteines-C43 and C51 in human VKORC1-conserved in all VKORC1s,
      essential for the activity of vitamin K epoxide reduction? RESULTS: We used our
      recently developed cell-based assay to compare the function of VKORHs to that of
      human VKORC1 in mammalian cells. We identified for the first time a VKORH (from
      Mycobacterium tuberculosis [Mt-VKORH]) that can function in the mammalian vitamin
      K cycle with vitamin K epoxide or vitamin K as substrate. Consistent with our
      previous in vitro results, the loop cysteines of human VKORC1 are not essential
      for its activity in vivo. Moreover, the corresponding loop cysteines of Mt-VKORH
      (C57 and C65), which are essential for its activity in disulfide bond formation
      during protein folding in Escherichia coli, are not required in the mammalian
      vitamin K cycle. INNOVATION AND CONCLUSIONS: Our results indicate that VKORC1 in
      eukaryotes and Mt-VKORH in bacteria, that is, in their respective native
      environments, employ apparently different mechanisms for electron transfer.
      However, when Mt-VKORH is in the mammalian cell system, it employs a mechanism
      similar to that of VKORC1.

PMID- 21939389
TI  - Common data elements for pediatric traumatic brain injury: recommendations from
      the working group on demographics and clinical assessment.
AB  - The Common Data Elements (CDEs) initiative is a National Institutes of Health
      (NIH) interagency effort to standardize naming, definitions, and data structure
      for clinical research variables. Comparisons of the results of clinical studies
      of neurological disorders have been hampered by variability in data coding,
      definitions, and procedures for sample collection. The CDE project objective is
      to enable comparison of future clinical trials results in major neurological
      disorders, including traumatic brain injury (TBI), stroke, multiple sclerosis,
      and epilepsy. As part of this effort, recommendations for CDEs for research on
      TBI were developed through a 2009 multi-agency initiative. Following the initial
      recommendations of the Working Group on Demographics and Clinical Assessment, a
      separate workgroup developed recommendations on the coding of clinical and
      demographic variables specific to pediatric TBI studies for subjects younger than
      18 years. This article summarizes the selection of measures by the Pediatric TBI
      Demographics and Clinical Assessment Working Group. The variables are grouped
      into modules which are grouped into categories. For consistency with other CDE
      working groups, each variable was classified by priority (core, supplemental, and
      emerging). Templates were produced to summarize coding formats, guide selection
      of data points, and provide procedural recommendations. This proposed
      standardization, together with the products of the other pediatric TBI working
      groups in imaging, biomarkers, and outcome assessment, will facilitate multi
      center studies, comparison of results across studies, and high-quality meta
      analyses of individual patient data.

PMID- 21939390
TI  - Multicenter evaluation of the course of coagulopathy in patients with isolated
      traumatic brain injury: relation to CT characteristics and outcome.
AB  - This prospective multicenter study investigated the association of the course of
      coagulation abnormalities with initial computed tomography (CT) characteristics
      and outcome in patients with isolated traumatic brain injury (TBI). Patient
      demographics, coagulation parameters, CT characteristics, and outcome data of
      moderate and severe TBI patients without major extracranial injuries were
      prospectively collected. Coagulopathy was defined as absent, early but temporary,
      delayed, or early and sustained. Delayed/sustained coagulopathy was associated
      with a higher incidence of disturbed pupillary responses (40% versus 27%;
      p<0.001) and higher Traumatic Coma Data Bank (TCDB) CT classification (5 (2-5)
      versus 2 (1-5); p=0.003) than in patients without or with early, but short
      lasting coagulopathy. The initial CT of patients with delayed/sustained
      coagulopathy more frequently showed intracranial hemorrhage and signs of raised
      intracranial pressure (ICP) compared to patients with early coagulopathy only.
      This was paralleled by higher in-hospital mortality rates (51% versus 33%;
      p<0.05), and poorer 6-month functional outcome in patients with delayed/sustained
      coagulopathy. The relative risk for in-hospital mortality was particularly
      related to disturbed pupillary responses (OR 8.19; 95% CI 3.15,21.32; p<0.001),
      early, short-lasting coagulopathy (OR 6.70; 95% CI 1.74,25.78; p=0.006), or
      delayed/sustained coagulopathy (OR 5.25; 95% CI 2.06,13.40; p=0.001).
      Delayed/sustained coagulopathy is more frequently associated with CT
      abnormalities and unfavorable outcome at 6 months after TBI than early, short
      lasting coagulopathy. Our finding that not only the mere presence but also the
      time course of coagulopathy holds predictive value for patient outcome underlines
      the importance of systematic hemostatic monitoring over time in TBI.

PMID- 21939391
TI  - Ghrelin prevents disruption of the blood-brain barrier after traumatic brain
      injury.
AB  - Significant effort has been focused on reducing neuronal damage from post
      traumatic brain injury (TBI) inflammation and blood-brain barrier (BBB)-mediated
      edema. The orexigenic hormone ghrelin decreases inflammation in sepsis models,
      and has recently been shown to be neuroprotective following subarachnoid
      hemorrhage. We hypothesized that ghrelin modulates cerebral vascular permeability
      and mediates BBB breakdown following TBI. Using a weight-drop model, TBI was
      created in three groups of mice: sham, TBI, and TBI/ghrelin. The BBB was
      investigated by examining its permeability to FITC-dextran and through
      quantification of perivascualar aquaporin-4 (AQP-4). Finally, we immunoblotted
      for serum S100B as a marker of brain injury. Compared to sham, TBI caused
      significant histologic neuronal degeneration, increases in vascular permeability,
      perivascular expression of AQP-4, and serum levels of S100B. Treatment with
      ghrelin mitigated these effects; after TBI, ghrelin-treated mice had vascular
      permeability and perivascular AQP-4 and S100B levels that were similar to sham.
      Our data suggest that ghrelin prevents BBB disruption after TBI. This is evident
      by a decrease in vascular permeability that is linked to a decrease in AQP-4.
      This decrease in vascular permeability may diminish post-TBI brain tissue damage
      was evident by decreased S100B.

PMID- 21939392
TI  - Aquaporin-4 Reduces Post-Traumatic Seizure Susceptibility by Promoting Astrocytic
      Glial Scar Formation in Mice.
AB  - Seizures are important neurologic complications following traumatic brain injury
      (TBI) and are reported for up to 50% of patients with TBI. Despite several
      studies, no drug strategy has been able to alter the biological events leading to
      epileptogenesis. The glial water channel aquaporin-4 (AQP4) was shown to
      facilitate cytotoxic cell swelling in ischemia and glial scar formation following
      stab wound injury. In this study, we examined post-traumatic seizure
      susceptibility of AQP4-deficient mice (AQP4-/-) after injection of
      pentylenetetrazole (PTZ) 1 month after controlled cortical impact (CCI) and
      compared them to wild-type sham injury controls. After PTZ injection, AQP4-/-
      mice demonstrated dramatically shortened seizure latency (120 +/- 40 seconds vs.
      300 +/- 70 seconds, p < 0.001) and increased seizure severity (grade 7.5 +/- 0.4
      vs. 5.8 +/- 0.4, p < 0.001) compared to their wild-type counterparts.
      Morphometric analysis demonstrated a significant two-fold reduction in
      astrocytosis with concomitant increase in microgliosis in injured AQP4-null mice
      compared to their injured wild-type counterparts (44 +/- 2 cells/hpf vs. 24 +/- 3
      cells/hpf, respectively, p < 0.0001). Minocycline, an inhibitor of microglia,
      reversed the post-TBI epilepsy phenotype of AQP4-null mice. After minocycline
      treatment, AQP4-/- mice demonstrated similar latency of seizures evoked by PTZ
      (723 +/- 35 seconds vs. 696 +/- 38 seconds, p > 0.05) and severity of seizures
      evoked by PTZ (grade 4 +/- 0.5 vs. 3.81 +/- 0.3, p > 0.05) compared to wild-type
      counterparts. Immunohistochemical analysis demonstrated decreased immunostaining
      of microglia to levels comparable to wild-type (12 +/- 2 cells/hpf vs. 11 +/- 4
      cells/hpf, respectively, p > 0.05). Taken together, these results suggest a
      protective role of AQP4 in post-traumatic seizure susceptibility by promoting
      astrogliosis, formation of a glial scar, and preventing microgliosis.

PMID- 21939394
TI  - Variability in the treatment of acute spinal cord injury in the United Kingdom:
      results of a national survey.
AB  - The aim of this study was to examine how traumatic spinal cord injury is managed
      in the United Kingdom via a questionnaire survey of all neurosurgical units. We
      contacted consultant neurosurgeons and neuroanesthetists in all neurosurgical
      centers that manage patients with acute spinal cord injury. Two clinical
      scenarios-of complete and incomplete cervical spinal cord injuries-were given to
      determine local treatment policies. There were 175 responders from the 33 centers
      (36% response rate). We ascertained neurosurgical views on urgency of transfer,
      timing of surgery, nature and aim of surgery, as well as neuroanesthetic views on
      type of anesthetic, essential intraoperative monitoring, drug treatment, and
      intensive care management. Approximately 70% of neurosurgeons will admit patients
      with incomplete spinal cord injury immediately, but only 40% will admit patients
      with complete spinal cord injury immediately. There is no consensus on the timing
      or even the role of surgery for incomplete or complete injuries. Most (96%)
      neuroanesthetists avoid anesthetics known to elevate intracranial pressure. What
      was deemed essential intraoperative monitoring, however, varied widely. Many
      (22%) neuroanesthetists do not routinely measure arterial blood pressure
      invasively, central venous pressure (85%), or cardiac output (94%) during
      surgery. There is no consensus among neuroanesthetists on the optimal levels of
      arterial blood pressure, or oxygen and carbon dioxide partial arterial pressure.
      We report wide variability among U.K. neurosurgeons and neuroanesthetists in
      their treatment of acute traumatic spinal cord injury. Our findings reflect the
      lack of Class 1 evidence that early surgical decompression and intensive medical
      management of patients with spinal cord injury improves neurological outcome.

PMID- 21939393
TI  - Hypersensitive glutamate signaling correlates with the development of late-onset
      behavioral morbidity in diffuse brain-injured circuitry.
AB  - In diffuse brain-injured rats, robust sensory sensitivity to manual whisker
      stimulation develops over 1 month post-injury, comparable to agitation expressed
      by brain-injured individuals with overstimulation. In the rat, whisker
      somatosensation relies on thalamocortical glutamatergic relays between the
      ventral posterior medial (VPM) thalamus and barrel fields of somatosensory cortex
      (S1BF). Using novel glutamate-selective microelectrode arrays coupled to
      amperometry, we test the hypothesis that disrupted glutamatergic
      neurotransmission underlies the whisker sensory sensitivity associated with
      diffuse brain injury. We report hypersensitive glutamate neurotransmission that
      parallels and correlates with the development of post-traumatic sensory
      sensitivity. Hypersensitivity is demonstrated by significant 110% increases in
      VPM extracellular glutamate levels, and 100% increase in potassium-evoked
      glutamate release in the VPM and S1BF, with no change in glutamate clearance.
      Further, evoked glutamate release showed 50% greater sensitivity to a calcium
      channel antagonist in brain-injured over uninjured VPM. In conjunction with no
      changes in glutamate transporter gene expression and exogenous glutamate
      clearance efficiency, these data support a presynaptic origin for enduring post
      traumatic circuit alterations. In the anatomically-distinct whisker circuit, the
      injury-induced functional alterations correlate with the development of late
      onset behavioral morbidity. Effective therapies to modulate presynaptic glutamate
      function in diffuse-injured circuits may translate into improvements in essential
      brain function and behavioral performance in other brain-injured circuits in
      rodents and in humans.

PMID- 21939395
TI  - Spinal cord injury triggers an intrinsic growth-promoting state in nociceptors.
AB  - Although most investigations of the mechanisms underlying chronic pain after
      spinal cord injury (SCI) have examined the central nervous system (CNS), recent
      studies have shown that nociceptive primary afferent neurons display persistent
      hyperexcitability and spontaneous activity in their peripheral branches and
      somata in dorsal root ganglia (DRG) after SCI. This suggests that SCI-induced
      alterations of primary nociceptors contribute to central sensitization and
      chronic pain after SCI. Does SCI also promote growth of these neurons' fibers, as
      has been suggested in some reports? The present study tests the hypothesis that
      SCI induces an intrinsic growth-promoting state in DRG neurons. This was tested
      by dissociating DRG neurons 3 days or 1 month after spinal contusion injury at
      thoracic level T10 and measuring neuritic growth 1 day later. Neurons cultured 3
      days after SCI exhibited longer neurites without increases in branching
      ("elongating growth"), compared to neurons from sham-treated or untreated (naive)
      rats. Robust promotion of elongating growth was found in small and medium-sized
      neurons (but not large neurons) from lumbar (L3-L5) and thoracic ganglia
      immediately above (T9) and below (T10-T11) the contusion site, but not from
      cervical DRG. Elongating growth was also found in neurons immunoreactive to
      calcitonin gene-related peptide (CGRP), suggesting that some of the neurons
      exhibiting enhanced neuritic growth were nociceptors. The same measurements made
      on neurons dissociated 1 month after SCI revealed no evidence of elongating
      growth, although evidence for accelerated initiation of neurite outgrowth was
      found. Under certain conditions this transient growth-promoting state in
      nociceptors might be important for the development of chronic pain and
      hyperreflexia after SCI.

PMID- 21939396
TI  - Wound contraction is significantly reduced by the use of microcarriers to deliver
      keratinocytes and fibroblasts in an in vivo pig model of wound repair and
      regeneration.
AB  - In full-thickness injuries caused by extensive burns or penetrating traumatic
      injuries, the natural epidermal stem cell niche is destroyed, and wound healing
      occurs through migration of cells from the wound edges and wound contraction.
      This can lead to significant contracture formation, especially in large full
      thickness injuries, causing lack of mobility and pain. Contraction is reduced
      when wounds are treated using split-thickness skin grafts (STSG) or dermal
      substitutes, particularly in combination with cultured autologous keratinocytes,
      delivered as confluent sheets or sprayed as a single cell suspension (SAK). Here,
      we show that the application of keratinocytes alone or keratinocytes with
      fibroblasts, delivered on microcarriers, in combination with STSG or a dermal
      substitute, significantly reduces contraction of wounds in vivo in a porcine
      model of wound repair and regeneration. A decrease in alpha-smooth muscle actin
      positive myofibroblasts, the cell type responsible for wound contraction,
      accompanies the reduction in contraction. These findings demonstrate the
      potential for a significant clinical advantage in the treatment of full-thickness
      injuries.

PMID- 21939397
TI  - Spatial and temporal expression of molecular markers and cell signals during
      normal development of the mouse patellar tendon.
AB  - Tendon injuries are common clinical problems and are difficult to treat. In
      particular, the tendon-to-bone insertion site, once damaged, does not regenerate
      its complex zonal arrangement. A potential treatment for tendon injuries is to
      replace injured tendons with bioengineered tendons. However, the bioengineering
      of tendon will require a detailed understanding of the normal development of
      tendon, which is currently lacking. Here, we use the mouse patellar tendon as a
      model to describe the spatial and temporal pattern of expression of molecular
      markers for tendon differentiation from late fetal life to 2 weeks after birth.
      We found that collagen I, fibromodulin, and tenomodulin were expressed throughout
      the tendon, whereas tenascin-C, biglycan, and cartilage oligomeric protein were
      concentrated in the insertion site during this period. We also identified
      signaling pathways that are activated both throughout the developing tendon, for
      example, transforming growth factor beta and bone morphogenetic protein, and
      specifically in the insertion site, for example, hedgehog pathway. Using a mouse
      line expressing green fluorescent protein in all tenocytes, we also found that
      tenocyte cell proliferation occurs at highest levels during late fetal life, and
      declines to very low levels by 2 weeks after birth. These data will allow both
      the functional analysis of specific signaling pathways in tenocyte development
      and their application to tissue-engineering studies in vitro.

PMID- 21939399
TI  - A randomized trial of training the non-dominant upper extremity to enhance
      laparoscopic performance.
AB  - INTRODUCTION: In laparoscopy, the surgeon's dominant arm will execute difficult
      tasks with less effort compared to the non-dominant arm. This leads to a relative
      overuse of muscles on this side. We hypothesized that training the non-dominant
      arm would improve laparoscopic skills. MATERIAL AND METHODS: At baseline, all
      participants performed three validated tasks on a virtual reality simulator.
      After randomization, subjects in the intervention group were assigned training
      tasks. All these tasks had to be performed with the non-dominant hand. Within a
      week after a three-week study period, participants performed the same three tasks
      as before. RESULTS: Twenty-six participants were included, 13 in each group. At
      baseline, there were no differences between groups on all tested parameters.
      Compliance to training tasks was good. At the end of three weeks, subjects in
      both groups showed similar improvement of skills on the non-dominant side. On the
      dominant side, however, subjects in the training group showed significant better
      improvement of skills on four out of eight parameters. CONCLUSION: Specific
      training of the non-dominant upper extremity appears to lead to improvement of
      skills on the dominant side, a phenomenon known in literature as intermanual
      transfer of skill learning. To improve laparoscopic skills, bimanual training is
      recommended.

PMID- 21939398
TI  - The effects of anti-inflammatory and anti-angiogenic DNA vaccination on diabetic
      nephropathy in rats.
AB  - Inflammation and angiogenesis play a crucial role in the pathomechanism of
      diabetic nephropathy. Monocyte chemoattractant protein 1 (MCP) is a key regulator
      of the immune system in kidneys, and its inhibition with a dominant-negative
      mutant lacking the N-terminal amino acids 2-8 (7ND) reduces renal fibrosis.
      Angiomotin (Amot) is a novel angiogenesis modulator. We studied the effects of
      inhibition of Amot and MCP using DNA vaccination on incipient diabetic
      nephropathy in rats. Plasmid DNA (with either 7ND or human Amot) was
      electroporated twice into hind-limb muscles of rats with streptozotocin-induced
      diabetes mellitus. Sham-electroporated diabetic rats and healthy animals served
      as controls. After 4 months, renal histology and biochemical analyses were
      performed. In sham-electroporated diabetic rats, glomerular histology revealed
      pathological changes. 7ND and Amot treatments reduced glomerular hypertrophy and
      periodic acid-Schiff positivity. In both treated groups, the expression of
      profibrotic (transforming growth factor-beta, collagen 1), proinflammatory
      (interleukin-6, tumor necrosis factor-alpha), and proangiogenic (vascular
      endothelial growth factor) genes in the renal cortex was lower than in the
      diabetic group without treatment. The mentioned renoprotective effects could be
      mediated via higher total antioxidant capacity and improved glycemic control.
      Anti-angiogenic and anti-inflammatory DNA vaccination ameliorates the progression
      of glomerular pathology in an animal model of diabetic nephropathy.

PMID- 21939400
TI  - Comparative study of the intravenous chemoprophylaxix versus local Sulmycin(r)
      Implant E Sponge use in vaginal hysterectomy.
AB  - OBJECTIVE: The aim of this comparative study was to ascertain the efficacy of the
      Sulmycin(r) Implant E, an antiseptic sponge, on the incidence of peri- and
      postoperative morbidity in patients subjected to vaginal hysterectomy. MATERIAL
      AND METHODS: This eleven-year study included 228 patients undergoing vaginal
      hysterectomy. The patients were divided into two groups. Group A included 169
      participants with benign diseases (fibroids, dysfunctional uterine bleeding and
      prolapse) and group B included 59 patients with early stage endometrial cancer or
      atypical hyperplasia. Women of both groups were further divided into three
      subgroups: (a) receiving a single dose of intravenous cefuroxime (2 gr) (group A:
      55, group B: 19), (b) receiving three doses of intravenous cefuroxime (2 gr)
      (group A: 54, group B: 19), and (c) locally placed a collagen sponge containing
      gentamycin (Sulmycin(r) Implant E) (group A: 60, group B: 21). RESULTS: The
      number of postoperative infections (mainly urinary tract infections) did not
      differ between women of the three subgroups of patients in both groups. There
      were no important differences affecting the postoperative hospitalization,
      healing procedure and adhesion of the cuff between women of the three subgroups
      in both groups. CONCLUSION: The local chemoprophylaxis with Sulmycin(r) Implant
      E, a collagen sponge containing gentamycin and placed on the vaginal cuff, is
      well tolerated and equally effective as intravenous antibiotics.

PMID- 21939402
TI  - Some patient-related factors associated with late access to ART in China's free
      ART program.
AB  - Highly active antiretroviral therapy (HAART) has become widely available in China
      during the past seven years. However, many patients still initiate treatment at
      very late stages. To understand the distribution of baseline CD4 and factors
      associated with late antiretroviral therapy (ART) access, the National Free ART
      Database was retrospectively reviewed and a total of 49,321 HIV/AIDS patients
      were identified in this study based on the following inclusion criteria: (1) age
      >=18; (2) initiated HAART between 1 July, 2006 and 31 December, 2009; (3) have
      recorded baseline CD4 cell count. This study showed that although both the median
      and mean baseline CD4 increased consistently over the study period, there were
      still about 30% of HIV/AIDS patients accessing ART at a very late stage (CD4 <=
      50 ul) in 2009. Risk factors for late ART access included being male, single,
      having a short time interval between HIV diagnosis and treatment, and being
      infected through heterosexual contact. Being infected through injection drug use
      and homosexual contact were protective. Transmission route and marriage status
      showed different effects in a gender stratified analysis. A strengthened HIV
      testing and screening program is the key to improving the accessibility of ART
      and populations that are vulnerable to sexual transmission of HIV should be the
      primary target of the program.

PMID- 21939401
TI  - What do we know about older adults and HIV? A review of social and behavioral
      literature.
AB  - The fastest growing segment of the United States HIV population is people aged 50
      and older. This heterogeneous group includes people with diverse pathways into
      HIV positive status in later life, including aging with the disease as well as
      later life-acquired infections. As people with HIV live into older ages, solving
      problems of successful secondary prevention and ongoing treatment requires more
      specific knowledge of the particular aging-related contextual sociocultural,
      psychosocial, and personal factors salient to the situations of persons living
      with HIV. Greater knowledge of these factors will help solve challenges to
      reducing psychological burden and promoting health maintenance for people with
      HIV. Yet, the current literature on aging and HIV remains nascent. To assess the
      state of knowledge of the sociocultural and behavioral factors associated with
      aging with HIV, we conducted a systematic critical content review of peer
      reviewed social and behavioral research on aging and HIV to answer the question,
      "How have older age, and social, cultural, and behavioral aspects of the
      intersection of HIV and age been addressed in the literature?" We searched First
      Search, Proquest, Psych Info, Pub Med, Wilson Select Plus, and World Cat and
      identified 1549 articles. We then reviewed these to select peer-reviewed articles
      reporting results of research on the social and behavioral aspects of living with
      HIV at age 50 and older. Fifty-eight publications were identified that met study
      inclusion criteria. While few publications reported clear age-related
      differences, there were significant ethnic differences in living with HIV in
      later life and also differences among older people when groups were defined by
      mode of transmission. Findings are discussed in light of constructs from
      gerontology which may contribute to clarifying how later life, life course stage,
      and psychological development intersect with, influence, and are influenced by
      HIV disease and long-term anti-retroviral therapy use.

PMID- 21939403
TI  - Barriers to antiretroviral adherence in HIV-positive patients receiving free
      medication in Kayunga, Uganda.
AB  - Global and local efforts have been devoted to increase the supply of
      antiretroviral therapy (ART) in sub-Saharan Africa. Recent qualitative studies
      suggest that even with free ART, patients may fail to adhere to medication
      because of socioeconomic barriers such as transportation costs to clinics. The
      aim of this study was to measure adherence in a population of patients receiving
      free ART and to examine barriers to adherence. Adherence was measured using the
      pill count and self-report methods among 140 HIV-positive patients at four PEPFAR
      facilitated ART clinics in Kayunga, a rural district in Uganda. Self-report was
      also used to examine reasons for non-adherence. Pill count adherence estimates
      revealed that 86.4% of the patients were adherent (>=95%) in the past six months.
      Self-report estimates showed that all the patients were adherent in the past six
      months with average adherence of 99.7%+/-0.6. The main reasons for non-adherence
      were being away from medication at dose time (29.4%) and forgetting to take pills
      (27.5%). Lack of access to food and transportation costs accounted for 11.7% and
      7.8% of non-adherence, respectively. Patients with 100% adherence reported lack
      of access to food as the main challenge they had to overcome to stay adherent.
      Patients attending the rural clinic were significantly less adherent to ART than
      patients at the Kayunga district capital [OR 0.046 (0.008-0.269)]. The study
      revealed that the greatest patient-perceived challenge to adherence in this
      population is the lack of access to food; however, the immediate reasons for non
      adherence were found to be forgetfulness and being away from medication at dose's
      time. These results suggest that interventions tackling lack of access to food
      are necessary, but interventions addressing forgetfulness and being away from
      medication at dose's time would be the most effective in enhancing adherence
      inpatients receiving free ART.

PMID- 21939404
TI  - Gender differences in HIV manifestations at presentation to care and continuity
      of care among HIV-infected persons in Taiwan.
AB  - The study aimed to compare the gender difference in clinical manifestations at
      time of HIV diagnosis and after one year of antiretroviral therapy, and to
      determine the influence of gender on HIV care continuity. A retrospective study
      was conducted using chart review of adults diagnosed with HIV infection from 1993
      2008 at a university-affiliated AIDS-designated hospital in Taiwan. Men who
      acknowledged having sex with men were excluded in order to compare the gender
      differences among patients with similar routes of HIV transmission and social
      context. Of the 682 patients with HIV, 86.6% were men. There were no significant
      gender differences in clinical, immunological or virological parameters at
      baseline. After one year of antiretroviral therapy, the curves of changes in CD4
      cell counts in men and women were parallel over time. Continuity of care,
      referring to at least one appointment in each six-month window during 2005-2008,
      was significantly associated with age >50 years (OR = 2.54, 95% CI: 1.04-6.16),
      being enrolled in the case management programme (OR = 4.93, 95% CI: 2.53-9.62),
      acquisition of HIV via heterosexual contact (OR = 3.63, 95% CI: 1.38-9.55), CD4
      lymphocyte count <200 counts/mm(3) at baseline (OR = 3.09, 95% CI: 1.38-6.96),
      being on highly active antiretroviral therapy (OR = 4.77, 95% CI: 2.37-9.59), and
      with sero-discordant partners (OR = 2.51, 95% CI: 1.07-5.87). The findings
      indicate that gender does not appear to be associated with HIV disease
      manifestations and continuity of care. Further research to develop optimal
      methods to retain patients in HIV care is needed.

PMID- 21939405
TI  - Testing theoretical network classes and HIV-related correlates with latent class
      analysis.
AB  - Scientists designing network-based interventions intending to improve the
      adoption or maintenance of healthy behaviors are well-advised to classify
      potential adopters into network roles, such as opinion leaders, brokers, members,
      and isolates, and to work closely with existing opinion leaders. In past studies
      focusing on HIV, opinion-leader interventions have had mixed results. This may be
      addressed, in part, by empirically validating these network roles. To this end,
      we used latent class analysis to test whether people's social connections fall
      into mutually exclusive and exhaustive subgroups of social capital that represent
      theorized network roles well with a dataset collected in Nyangana, Namibia (n =
      400). A four-class model best fits the dataset, but the categories identified do
      not clearly represent the theorized roles. Rather, this study revealed the
      following four network classes: single-group members (59%), connectors (24%),
      single-group loyalists (15%), and selective connectors (2%). The implications of
      their findings for opinion-leader interventions focused on HIV are discussed.

PMID- 21939406
TI  - Implementing routine provider-initiated HIV testing in public health care
      facilities in Kenya: a qualitative descriptive study of nurses' experiences.
AB  - Routine "provider-initiated testing and counselling" (PITC) for HIV has been
      implemented amidst concern over how consent, confidentiality and counselling (the
      3Cs) can be maintained in under-resourced health care settings. In Kenya, PITC
      has been rolled out since 2005, HIV prevalence is 7.1% and more than 86% of
      adults have not been tested. Kenyan nurses are the main cadre implementing PITC,
      but little is known about their experiences of incorporating HIV testing into
      everyday practice and the challenges faced in maintaining the 3Cs within their
      work environments. This study aimed to explore these issues and adopted a
      qualitative multi-method design using a convenience sampling approach. Two focus
      group discussions (total n=12) and 13 in-depth individual interviews were
      undertaken with nurses from 11 different public health care facilities in Nairobi
      and its surrounding areas (including in-patient and outpatient settings). Data
      were analysed thematically. Nurses identified a range of personal, client and
      health system challenges in the everyday application of PITC. These included (i)
      the contradictions of normalising a highly stigmatised disease and the difficulty
      in providing client-centred care within a routinised and target-oriented work
      culture; (ii) the challenge of dealing with ethically complex client situations
      in which the principles of the 3Cs could be difficult to uphold; and (iii) lack
      of time, resources, space and recognition within workplace environments
      (especially in-patient settings) that, likewise, led to problems with maintaining
      the 3Cs. In-patient nurses in particular identified problems associated with
      testing in a multi-disciplinary context, suggesting that other health
      professionals appeared to routinely flout the PITC guidelines. In conclusion,
      this study shows that the process of translating policy into practice is
      invariably complex and that more research is needed to explore PITC practices,
      particularly in in-patient settings. Nurses require supervision and support to
      negotiate the challenges and to fulfil their roles effectively.

PMID- 21939407
TI  - Measurement of retention in care among adults infected with HIV in an urban
      clinic.
AB  - Adults infected with HIV live longer when they receive regular medical care, yet
      many adults are not retained in care. Providers measure retention in order to
      evaluate interventions to improve retention and quality of HIV care. However,
      multiple measures for retention exist. This study compares two methods of
      operationalizing retention and evaluates the contribution of individual
      characteristics on the likelihood of retention. A chart review was performed for
      a random sample of 212 active clients of an urban HIV primary care clinic. Data
      on clinic utilization, sex, age, race, mental illness, substance use, AIDS
      diagnosis, language, and housing were collected for each participant. Clinic
      utilization data were used to classify participants for retention status and to
      score them by frequency of visits. Binary logistic regression analysis was
      compared with ordinal logistic regression analysis, using distinct retention
      measures as outcome variables. In the binary model, those with a history of
      substance use were about half as likely to be retained (OR 0.52, 95% CI 0.29
      0.94) and those with an AIDS diagnosis were more than twice as likely to be
      retained (OR 2.18, 95% CI 1.17-4.09). These characteristics were significant
      predictors in the ordinal model, with the additional finding that those reporting
      English as a primary language were less likely to have higher retention scores
      (OR 0.40, 95% CI 0.19-0.84). An ordinal score for retention can identify
      unexpected predictors, but a dichotomous measure of retention may be easier to
      use and interpret for providers involved in retention-related quality improvement
      activities.

PMID- 21939408
TI  - Time to first annual HIV care visit and associated factors for patients in care
      for HIV infection in 10 US cities.
AB  - BACKGROUND: Visiting a medical provider less frequently than clinical
      circumstances would suggest is appropriate has been reported to be associated
      with worse clinical outcomes for patients living with HIV infection. Patients
      with less frequent attendance to HIV care also may be systematically
      underrepresented in research or surveillance studies that enroll patients
      sequentially over a specified enrollment period - for example several months. For
      both reasons, understanding factors associated with time to care visit is
      important. METHODS: We used data from the Adult and Adolescent Spectrum of HIV
      Disease (ASD) project, a multi-site clinical outcomes surveillance system that
      enrolled and followed patients in care for HIV prospectively from 1990 to 2004.
      For this analysis, we used data from all patients observed in ASD at least one
      time before 1 January 2003, and who had at least one HIV care visit in 2003. We
      documented time to first annual HIV care visit for each patient, and used Kaplan
      Meier plots and proportional hazards regression to describe factors associated
      with longer time to care visit. RESULTS: A total of 12,135 patients had >=1 care
      visit during 2003 and were included in the analysis. Of these, 81%, 88%, and 95%
      had their first visit within three, four, and six months, respectively. In
      multivariate analysis, having a delayed (later) care visit was associated with
      not ever having had an AIDS diagnosis, having an HIV RNA concentration >=10,000
      copies/mL, having a current CD4 count <100 cells/uL, having no health insurance,
      and not being currently prescribed antiretroviral therapy. Having a delayed care
      visit was not associated with race/ethnicity or age. CONCLUSIONS: Having a
      delayed first annual HIV care visit was associated with higher viremia, lower CD4
      cell count, and lack of health insurance. Interventions to address these factors
      are likely to ameliorate some of the consequences of HIV. For studies enrolling
      patients in care for HIV over a finite time period, an enrollment period of four
      six months should sufficiently reflect the patient population seen in a one-year
      period, including those attending care infrequently.

PMID- 21939409
TI  - Access of people living with HIV to infertility services: perspective of
      Brazilian healthcare professionals.
AB  - OBJECTIVE: To evaluate the perspective of professionals in university and public
      assisted reproductive technology (ART) and HIV/AIDS services in Brazil, on the
      demand of people living with HIV wishing to conceive. DESIGN: Mixed qualitative
      and quantitative, descriptive, cross-sectional and case study. METHODS: The
      quantitative component was based on telephone interviews to women's health and
      HIV/AIDS program managers at state and municipal level. For the qualitative case
      study, semi-structured interviews were conducted with health professionals of ART
      and HIV/AIDS services. RESULTS: Only one university ART service provided care for
      seropositive couples, but 64% of the HIV/AIDS services at state level and 73% of
      municipal HIV/AIDS services offered reproductive counseling focused on preventing
      pregnancy. Difficulty in discussing desire to conceive, lack of political
      decision and of human and financial resources were the main reasons given by
      service managers for not offering the opportunity for HIV couples. Lack of
      appropriate referrals and of updated knowledge on reproductive options were
      constrains according to the interviews. CONCLUSION: Desire to reproduce among
      people living with HIV is poorly addressed in public services in Brazil.

PMID- 21939411
TI  - Risk and predictive factors of hypoalbuminemia in cancer patients following
      extensive abdominal surgery despite total parenteral nutritional support.
AB  - Postoperative hypoalbuminemia is associated with adverse outcomes, particularly
      in cancer patients. The risk and predictors of hypoalbuminemia in cancer patients
      following extensive abdominal surgery (EAS), despite total parenteral nutrition
      (TPN) support, were evaluated. A prospective cohort study (n = 115) was conducted
      in patients with gastrointestinal and/or urogenital malignancies following
      extensive (n = 81) or moderate (n = 34) abdominal surgery (mean age +/- standard
      deviation: 66.0 +/- 11.7 years). EAS patients received daily TPN, including 200
      mL of 5% human albumin solution. Serum albumin (SA) levels and hypoalbuminemia
      (SA < 3.5 g/dL) were assessed daily. EAS patients had an elevated risk of
      hypoalbuminemia during the first postoperative week [relative risk (RR): 3.12;
      95% confidence interval (95% CI): 1.64-5.91]. Postoperative hypoalbuminemia was
      associated with surgery duration (RR: 1.76; 95% CI: 1.32-2.36), preoperative SA
      (RR: 0.24; 95% CI: 0.11-0.55), blood (RR: 1.46; 95% CI: 1.04-2.04) and Ringer's
      lactated solution (RR: 1.52; 95% CI: 1.12-2.07) volumes transfused intra
      operatively. Therefore, despite TPN, cancer patients who underwent EAS had an
      elevated risk of postoperative hypoalbuminemia. Additional tailored nutritional
      support among this group is necessary to deter adverse clinical outcomes.

PMID- 21939412
TI  - Event-related potential correlates of suspicious thoughts in individuals with
      schizotypal personality features.
AB  - Suspiciousness is a common feature of schizophrenia. However, suspicious thoughts
      are also commonly experienced by the general population. This study aimed to
      examine the underlying neural mechanism of suspicious thoughts in individuals
      with and without schizotypal personality disorder (SPD)-proneness, using an event
      related potential (ERP) paradigm. Electroencephalography (EEG) was recorded when
      the "feeling of being seen through" was evoked in the participants. The findings
      showed a prominent positive deflection of the difference wave within the time
      window 250-400 ms after stimuli presentation in both SPD-prone and non-SPD-prone
      groups. Furthermore, the P3 amplitude was significantly reduced in the SPD-prone
      group compared to the non-SPD-prone group. The current density analysis also
      indicated hypoactivity in both frontal and temporal regions in the SPD-prone
      group, suggesting that the frontotemporal cortical network may play a role in the
      onset of suspicious thoughts. The P3 of difference wave was inversely correlated
      with the cognitive-perception factor and the suspiciousness/paranoid ideation
      trait, which provided preliminary electrophysiological evidence for the
      association of suspiciousness with SPD features.

PMID- 21939413
TI  - Platelet-type von Willebrand disease update: the disease, the molecule and the
      animal model.

PMID- 21939414
TI  - SALL4: finally an answer to the problem of expansion of hematopoietic stem cells?

PMID- 21939410
TI  - Pemphigus autoimmunity: hypotheses and realities.
AB  - The goal of contemporary research in pemphigus vulgaris and pemphigus foliaceus
      is to achieve and maintain clinical remission without corticosteroids. Recent
      advances of knowledge on pemphigus autoimmunity scrutinize old dogmas, resolve
      controversies, and open novel perspectives for treatment. Elucidation of intimate
      mechanisms of keratinocyte detachment and death in pemphigus has challenged the
      monopathogenic explanation of disease immunopathology. Over 50 organ-specific and
      non-organ-specific antigens can be targeted by pemphigus autoimmunity, including
      desmosomal cadherins and other adhesion molecules, PERP cholinergic and other
      cell membrane (CM) receptors, and mitochondrial proteins. The initial insult is
      sustained by the autoantibodies to the cell membrane receptor antigens triggering
      the intracellular signaling by Src, epidermal growth factor receptor kinase,
      protein kinases A and C, phospholipase C, mTOR, p38 MAPK, JNK, other tyrosine
      kinases, and calmodulin that cause basal cell shrinkage and ripping desmosomes
      off the CM. Autoantibodies synergize with effectors of apoptotic and oncotic
      pathways, serine proteases, and inflammatory cytokines to overcome the natural
      resistance and activate the cell death program in keratinocytes. The process of
      keratinocyte shrinkage/detachment and death via apoptosis/oncosis has been termed
      apoptolysis to emphasize that it is triggered by the same signal effectors and
      mediated by the same cell death enzymes. The natural course of pemphigus has
      improved due to a substantial progress in developing of the steroid-sparing
      therapies combining the immunosuppressive and direct anti-acantholytic effects.
      Further elucidation of the molecular mechanisms mediating immune dysregulation
      and apoptolysis in pemphigus should improve our understanding of disease
      pathogenesis and facilitate development of steroid-free treatment of patients.

PMID- 21939415
TI  - Combining proteasome with cell cycle inhibitors: a dual attack potentially
      applicable to multiple hematopoietic malignancies.

PMID- 21939417
TI  - Highlights in lymphoma: overview of the 11th International Conference on
      Malignant Lymphoma.
AB  - The 11th International Conference on Malignant Lymphoma (ICML), the main
      international forum devoted to basic and clinical research in lymphoid neoplasms,
      took place in Lugano, Switzerland, from 15 to 18 June 2011. In 2011, 3200 experts
      in lymphoma from 76 countries attended the meeting. ICML represents the most
      important forum for the discussion of all aspects relating to basic research,
      clinical data and results of trials in the treatment of malignant lymphoma
      worldwide. The incidence of Hodgkin's and non-Hodgkin's lymphoma is increasing.
      Treatment of lymphoma is heterogeneous, with effective results seen with standard
      chemotherapy, immunotherapy, high-dose chemotherapy with transplantation and
      radiotherapy. The biological basis of the growth of lymphoma explains the
      rationale for the introduction of experimental new drugs in monotherapy or in
      combination with consolidate schemes. The results have been promising and these
      issues were discussed during the meeting. On this basis, the ICML report was
      focused on the most topical, interesting or thought-provoking issues in the
      treatment of lymphoma.

PMID- 21939419
TI  - Bacterial contamination of platelet components: potential solutions to prevent
      transfusion-related sepsis.
AB  - Bacterial contamination of platelet components (PC) is the most prevalent risk
      for transfusion-transmitted infection. Based on the recent studies with optimal
      culture methods of expired PC, the prevalence of bacterial contamination is
      estimated to occur in approximately one in 750 to one in 1000 PC. Only within the
      last few years have the magnitude of the risks and the range of clinical outcomes
      associated with bacterial contamination been extensively characterized. Despite
      increased recognition of bacterial contamination of PC, transfusion-related
      sepsis is infrequently reported. This has largely been attributed to passive
      reporting systems, and low levels of clinical awareness for transfusion-related
      sepsis by primary care physicians. The risk for transfusion of contaminated PC
      has generally been characterized per component. Importantly, because patients
      require repeated transfusions of PC during a period of transfusion-dependent
      thrombocytopenia, it is appropriate to express the risk to receive a contaminated
      PC on a patient exposure basis. Assuming that the average hematology oncology
      patient may receive seven PC during a 28-day period of support, the risk of
      exposure to a contaminated PC is in the range of one in 150 per patient. This
      level of risk would not be acceptable for other intravenous medications. With
      increased appreciation of the risk of bacterial contamination, methods were
      developed to limit the risk of transfusion-transmitted bacteremia. This article
      focuses on those interventions that have been implemented in routine practice.
      The most important methods employed to mitigate the risk are improved skin
      disinfection, initial blood draw diversion, bacterial detection and pathogen
      inactivation/reduction. These technologies are now undergoing increased use in
      the clinical practice of transfusion medicine. With increased use, additional
      data are being generated to more fully characterize the effects of these
      interventions. Improved disinfection, blood diversion and bacterial detection
      have decreased, but not resolved the risk of bacterial contamination. Pathogen
      inactivation/reduction offers the potential for a further substantial decrease of
      the risk for transfusion of PC contaminated with bacteria.

PMID- 21939418
TI  - Rationale for a randomized controlled trial comparing two prophylaxis regimens in
      adults with severe hemophilia A: the Hemophilia Adult Prophylaxis Trial.
AB  - A major goal of comprehensive hemophilia care is to prevent occurrence of bleeds
      by prophylaxis or regular preventive factor, one or more times weekly. Although
      prophylaxis is effective in reducing bleeding and joint damage in children,
      whether it is necessary to continue into adulthood is not known. The purpose of
      this article is to describe a Phase III randomized controlled trial to evaluate
      prophylaxis comparing two dose regimens in adults with severe hemophilia A. I
      hypothesize that adults with mature cartilage and joints are less susceptible to
      joint bleeds and joint damage, and that once-weekly recombinant factor VIII
      prophylaxis, with up to two rescue doses per week, is as effective as thrice
      weekly prophylaxis in reducing bleeding frequency, but less costly and more
      acceptable, with higher quality of life. The ultimate goal of this project is to
      determine whether once-weekly prophylaxis is any worse than thrice-weekly
      prophylaxis in reducing joint bleeding frequency, while potentially utilizing
      less factor, at lower cost, leading to a better quality of life. This is an
      innovative concept, as it challenges the current paradigm of thrice-weekly
      prophylaxis in adults, which is based on dosing in children. Furthermore, this
      trial will assess interdose thrombin generation, a novel tissue factor-based
      assay of hemostasis, to determine if individualized thrombin generation can
      predict more individualized prophylaxis dosing, which would be practice changing.

PMID- 21939420
TI  - Transfusion medicine in trauma patients: an update.
AB  - In 2008, we reviewed the practical interface between transfusion medicine and the
      surgery and critical care of severely injured patients. Reviewed topics ranged
      from epidemiology of trauma to patterns of resuscitation to the problems of
      transfusion reactions. In the interim, trauma specialists have adopted damage
      control resuscitation and become much more knowledgeable and thoughtful about the
      use of blood products. This new understanding and the resulting changes in
      clinical practice have raised new concerns. In this update, we focus on which
      patients need damage control resuscitation, current views on the optimal form of
      damage control resuscitation with blood products, the roles of newer blood
      products, and appropriate transfusion triggers in the postinjury setting. We will
      also review the role of new technology in patient assessment, therapy and
      monitoring.

PMID- 21939422
TI  - Targeted molecular therapy in peripheral T-cell lymphomas.
AB  - Peripheral T-cell lymphomas (PTCLs) are rare neoplasms constituting a
      heterogeneous group of diseases. At present, available chemotherapy regimens that
      have improved outcomes in B-cell lymphomas appear to be less efficacious in the
      context of PTCLs and, thus, alternative strategies are warranted. In the last few
      years, based on the recent, deeper understanding of PTCL biology, several
      molecules and/or pathways have been proposed for targeted therapy in this
      setting, including surface antigens, tyrosine kinases, the NF-kappaB pathway,
      folate metabolism, histone modification and others. Of particular interest,
      histone deacetylase and proteasome inhibitors, as well as novel chemotherapeutic
      agents such as pralatrexate, have already demonstrated efficacy in PTCL therapy.
      In addition, a strong biological rationale and early clinical evidence supports
      the future study of tyrosine kinase inhibitors in this setting. In this article,
      the authors review the available literature on targeted therapy in PTCLs and
      also, based on their own experience, discuss potential opportunities in this
      intriguing area.

PMID- 21939423
TI  - The chemokine system in allogeneic stem-cell transplantation: a possible
      therapeutic target?
AB  - Further improvements in allogeneic stem-cell transplantation will probably depend
      on a better balance between immunosuppression to control graft-versus-host
      disease and immunological reconstitution sufficient to ensure engraftment,
      reduction of infection-related mortality and maintenance of post-transplant
      antileukemic immune reactivity. The chemokine network is an important part of the
      immune system, and, in addition, CXCL12/CXCR4 seem to be essential for
      granulocyte colony-stimulating factor-induced stem-cell mobilization. Partial ex
      vivo graft T-cell depletion based on the expression of specific chemokine
      receptors involved in T-cell recruitment to graft-versus-host disease target
      organs may also become a future therapeutic strategy; an alternative approach
      could be pharmacological inhibition (single-receptor inhibitors or dual-receptor
      inhibitors) in vivo of specific chemokine receptors involved in this T-cell
      recruitment. Future clinical studies should therefore be based on a better
      characterization of various immunocompetent cells, including their chemokine
      receptor profile, both in the allografts and during post-transplant
      reconstitution.

PMID- 21939425
TI  - Exposure to low level chronic radiation leads to adaptation to a subsequent acute
      X-ray dose and communication of modified acute X-ray induced bystander signals in
      medaka (Japanese rice fish, Oryzias latipes).
AB  - PURPOSE: To determine the effect of acute high dose X-rays on the direct and
      bystander response of chronically exposed medaka in vivo using the fish
      communication model. METHODS: Medaka were obtained from the Low Dose Rate
      Irradiation Facility (LoDIF) located at the Savannah River Ecology Laboratory
      (SREL), University of Georgia, Aiken, South Carolina, USA where they had been
      exposed over 264 days to cumulative total doses of 0, 0.03, 0.66 and 5.88 Gy.
      They were exposed to the acute dose at McMaster University and then allowed to
      swim with unexposed medaka. All groups were sacrificed and fins were cultured as
      explants and assayed using an established technique and reporter assay. RESULTS:
      Directly irradiated medaka with no chronic exposure showed a classic in vivo
      bystander response. Chronic pre-exposure resulted in a chronic dose-dependent
      increase in reporter cell survival in directly exposed fish. A 'pro-survival'
      response was also seen in the bystander fish. The proteins bcl-2 (b cell lymphoma
      2) and c-Myc (myelocytomatosis oncogene cellular) in tissue explants were good
      predictors of pro-life or pro-death signals. CONCLUSIONS: Environmentally
      relevant chronic exposure to medaka in vivo results in adaptive responses in fish
      subsequently irradiated with high acute doses and in communication of protective
      signals to fish swimming with exposed fish. The data have implications for
      interpretation of radiation effects in biota.

PMID- 21939426
TI  - Tilapia (Oreochromis mossambicus) allergens characterized by ELISA, SDS-PAGE, 2D
      gels, Western blotting and MALDI-TOF mass spectrometry.
AB  - Parvalbumins have long been identified as major allergens in fish, but our
      research has found that parvalbumins are not the main cause of allergic reactions
      to tilapia. After homogenization, proteins were extracted from freshwater tilapia
      to react with a pooled sera sample taken from patients (n = 20) tested to be
      allergic to tilapia. Enzyme-linked immunosorbent assay revealed immunoglobulin E
      antibody activity, followed by sodium dodecyl sulphate polyacrylamide gel
      electrophoresis, Western blot, 2D electrophoresis and matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry to carry out protein
      separation and analysis. Protein identification against different databases
      yielded three known high molecular weight proteins as tilapia allergens:
      chromosome undetermined SCAF7145, fructose-bisphosphate aldolase A and enolase 3
      (beta muscle). A fourth, new, unidentified protein with two T-cell receptors was
      discovered.

PMID- 21939421
TI  - Self-complementary adeno-associated viral vectors for gene therapy of hemophilia
      B: progress and challenges.
AB  - Therapies currently used for hemophilia involve injection of protein concentrates
      that are expensive, invasive and associated with side effects such as development
      of neutralizing antibodies (inhibitors) that diminish therapeutic efficacy. Gene
      transfer is an attractive alternative to circumvent these issues. However, until
      now, clinical trials using gene therapy to treat hemophilia have failed to
      demonstrate sustained efficacy, although a vector based on a self-complementary
      adeno-associated virus has recently shown promise. This article will briefly
      outline a novel gene-transfer approach using self-complementary adeno-associated
      viral vectors using hemophilia B as a target disorder. This approach is currently
      being evaluated in the clinic. We will provide an overview of the development of
      self-complementary adeno-associated virus vectors as well as preclinical and
      clinical data with this vector system.

PMID- 21939427
TI  - An update on computational oral absorption simulation.
AB  - INTRODUCTION: Within the last decades, computational models have developed
      rapidly and some of these models have proven useful in understanding how
      physiological, physicochemical and formulation factors affect oral drug
      absorption. Nowadays, complex computer-based absorption models are being used as
      standard tools in both academia and the pharmaceutical industry at several stages
      of the drug development process. AREAS COVERED: Areas covered include the
      progress of computational tools for predicting drug absorption. The various
      qualitative and quantitative approaches that have been proposed are summarized,
      with special emphasis on a key tool for predicting oral drug absorption,
      physiologically based pharmacokinetic modeling (PBPK). The theories of the
      different models are described and recent applications within drug research and
      development are summarized and evaluated. Additionally, the current state of
      computational absorption models is discussed, including areas for potential
      improvements. EXPERT OPINION: The field of pharmacokinetics modeling has
      undergone a major transformation over the last 10 - 20 years and there will most
      likely be even more exciting developments ahead. With the availability of generic
      physiologically based absorption models, more and more case examples using PBPK
      models have been published that demonstrate either improved ability to predict
      oral drug absorption or have allowed a more mechanistic interpretation of
      experimentally observed data.

PMID- 21939428
TI  - Venoms as a platform for human drugs: translating toxins into therapeutics.
AB  - INTRODUCTION: An extraordinarily diverse range of animals have evolved venoms for
      predation, defence, or competitor deterrence. The major components of most venoms
      are peptides and proteins that are often protease-resistant due to their
      disulfide-rich architectures. Some of these toxins have become valuable as
      pharmacological tools and/or therapeutics due to their extremely high specificity
      and potency for particular molecular targets. There are currently six FDA
      approved drugs derived from venom peptides or proteins. AREAS COVERED: This
      article surveys the current pipeline of venom-derived therapeutics and critically
      examines the potential of peptide and protein drugs derived from venoms. Emerging
      trends are identified, including an increasing industry focus on disulfide-rich
      venom peptides and the use of a broader array of molecular targets in order to
      develop venom-based therapeutics for treating a wider range of clinical
      conditions. EXPERT OPINION: Key technical advances in combination with a renewed
      industry-wide focus on biologics have converged to provide a larger than ever
      pipeline of venom-derived therapeutics. Disulfide-rich venom peptides obviate
      some of the traditional disadvantages of therapeutic peptides and some may be
      suitable for oral administration. Moreover, some venom peptides can breach the
      blood brain barrier and translocate across cell membranes, which opens up the
      possibility of exploiting molecular targets not previously accessible to peptide
      drugs.

PMID- 21939430
TI  - Novel 1,5-naphthyridine PI3Kdelta inhibitors, an evaluation of WO2011075628.
AB  - A small series of aryl(1-arylamino)ethyl,1,5-naphthyridine derivatives that
      selectively inhibit PI3Kdelta was prepared. The compounds are claimed to be
      useful in the treatment of cancer, inflammatory and autoimmune diseases. The
      compounds represent further variations around a structural motif explored in a
      number of previous applications by the applicant.

PMID- 21939431
TI  - Metabolic activation in drug-induced liver injury.
AB  - It is generally believed that metabolic bioactivation of drug molecules to form
      reactive metabolites, followed by their covalent binding to endogenous
      macromolecules, is one of the mechanisms that can lead to hepatotoxicity or
      idiosyncratic adverse drug reactions (IADRs). Although the role of bioactivation
      in drug-induced liver injury has been reasonably well established and accepted,
      and methodologies (e.g., structural alerts, reactive metabolite trapping, and
      covalent binding) continue to emerge in an attempt to detect the occurrence of
      bioactivation, the challenge remains to accurately predict the likelihood for
      idiosyncratic liver toxicity. Recent advances in risk-assessment methodologies,
      such as by the estimate of total body burden of covalent binding or by zone
      classification, taking the clinical dose into consideration, are positive steps
      toward improving risk assessment. The ability to better predict the potential of
      a drug candidate to cause IADRs will further be dependent upon a better
      understanding of the pathophysiological mechanisms of such reactions. Until a
      thorough understanding of the relationship between liver toxicity and the
      formation of reactive metabolites is achieved, it appears, at present, that the
      most practical strategy in drug discovery and development to reduce the
      likelihood of idiosyncratic liver toxicity via metabolic activation is to
      minimize or eliminate the occurrence of bioactivation and, at the same time, to
      maximize the pharmacological potency (to minimze the clinical dose) of the drug
      of interest.

PMID- 21939432
TI  - Central chorioretinopathy associated with topical use of minoxidil 2% for
      treatment of baldness.
AB  - PURPOSE: Minoxidil is one of the drugs approved for the treatment of androgenetic
      alopecia. This article presents a case of central serous chorioretinopathy after
      application of topical minoxidil solution. METHODS: We examined a 37-year-old man
      who complained of a positive relative scotoma, metamorphopsia and impaired dark
      adaptation involving the right eye. The patient reported an 8 month history of
      daily topical use but denied previous treatment with other drugs. Dilated fundus
      examination of right eye revealed central swelling located over the macula.
      Optical coherence tomography showed the presence of subretinal fluid. Fluorescein
      angiography disclosed one focal hyperfluorescent spot in the foveal area with
      minimal pigmentary changes limitated to that area. The patient was diagnosed with
      central serous chorioretinopathy (CSC) potentially related to an 8 month topical
      minoxidil solution administration. One month after the drug was discontinued,
      normal findings were found upon reexamination. The patient reported no previous
      episode of CSC. CONCLUSION: Major systemic side effects from topical solution of
      minoxidil are rare. To our knowledge, this is the first reported case of a
      central serous chorioretinopathy associated with long-term use of this drug.

PMID- 21939433
TI  - Acute and long-term transcriptional responses in sulfur mustard-exposed SKH-1
      hairless mouse skin.
AB  - Sulfur mustard (HD) ranks among the alkylating chemical warfare agents. Skin
      contact with HD produces an inflammatory response that evolves into separation at
      the epidermal-dermal junction conducting to blistering and epidermis necrosis. Up
      to now, current treatment strategies of HD burns have solely consisted in
      symptomatic management of skin damage. Therapeutic efficacy studies are still
      being conducted; classically using appropriate animal skin toxicity models. In
      order to substantiate the use of SKH-1 hairless mouse as an appropriate model for
      HD-induced skin lesions, we investigate the time-dependent quantitative gene
      expression of various selected transcripts associated to the dorsal skin exposure
      to HD saturated vapors. Using quantitative real time polymerase chain reaction
      (RT-qPCR), the expression of interleukins (IL-1beta and IL-6), tumor necrosis
      factor (TNF)-alpha, macrophage inflammatory proteins (MIP)-2alpha (also called
      Cxcl2) and MIP-1alphaR (also called Ccr1), matrix metalloproteases (MMP-9 and MMP
      2), laminin gamma2 monomer (Lamc2) and keratin (K)1 was determined up to 21 days
      after HD challenge in order to allow enough time for wound repair to begin.
      Specific transcript RT-qPCR analysis demonstrated that IL-6, IL-1beta, Ccr1,
      Cxcl2 mRNA levels increased as early as 6 h in HD-exposed skins and remained up
      regulated over a 14-day period. Topical application of HD also significantly up
      regulated MMP-9, TNF-alpha, and Lamc2 expression at specific time points. In
      contrast, MMP-2 mRNA levels remained unaffected by HD over the time-period
      considered, whereas that long-term study revealed that K1 mRNA level
      significantly increased only 21 days after HD challenge. Our study hereby
      provides first-hand evidence to substantiate a long period variation expression
      in the inflammatory cytokine, MMPs and structural components following cutaneous
      HD exposure in hairless mouse SKH-1. Our data credit the use of SKH-1 for
      investigating mechanisms of HD-induced skin toxicity and for the development of
      pharmacological countermeasures.

PMID- 21939434
TI  - Toxic anterior segment syndrome subsequent to pediatric cataract surgery.
AB  - OBJECTIVE: The aim of this study was to investigate possible risk factors and
      treatment outcomes for the development of toxic anterior segment syndrome (TASS)
      subsequent to pediatric cataract surgery. MATERIALS AND METHODS: Totally 893 eyes
      of 534 patients who underwent pediatric cataract surgery were evaluated
      retrospectively from the point of TASS development between 2006 and 2011. TASS
      was observed in 19 eyes of 13 patients. Properties of surgical materials used for
      these patients, postoperative symptoms and their initiation time, therapeutic
      approaches and results were evaluated. RESULTS: Lens aspiration, posterior
      capsulotomy and anterior vitrectomy was performed for 480 eyes and TASS developed
      in 12 eyes. However, TASS was observed in seven eyes of 413 eyes that underwent
      lens aspiration, posterior capsulotomy, anterior vitrectomy and intraocular lens
      (IOL) implantation. The factors that may cause TASS were evaluated. Materials
      used in surgery (intraocular irrigation fluids, viscoelastic materials,
      intracameral medications etc.) were the same, in all cases. But in all TASS
      cases, it has been noticed that ethylene oxide-sterilized vitrectomy packs were
      used for anterior vitrectomy. After the abolition of use of this material, we
      didn't see new TASS cases. Clinical improvement was achieved by treatment with
      0.1% dexamethasone, 0.3% ofloxasin and 5% NaCl in 18 eyes with TASS at mean
      duration of 6.4 +/- 4.7 (range, 2-16) weeks. Penetrating keratoplasty was
      performed to one eye of a patient with bilateral TASS due to unresponsiveness to
      medical management. CONCLUSION: Use of ethylene oxide-sterilized vitrectomy packs
      in pediatric cataract surgery is an important risk factor for the development of
      TASS. Although the majority of the patients with TASS after pediatric cataract
      surgery recover with medical therapy, a few cases may need penetrating
      keratoplasty due to irreversible corneal decompensation.

PMID- 21939436
TI  - Identification of novel small molecules that elevate Klotho expression.
AB  - The absence of Klotho (KL) from mice causes the development of disorders
      associated with human aging and decreased longevity, whereas increased expression
      prolongs lifespan. With age, KL protein levels decrease, and keeping levels
      consistent may promote healthier aging and be disease-modifying. Using the KL
      promoter to drive expression of luciferase, we conducted a high-throughput screen
      to identify compounds that activate KL transcription. Hits were identified as
      compounds that elevated luciferase expression at least 30%. Following validation
      for dose-dependent activation and lack of cytotoxicity, hit compounds were
      evaluated further in vitro by incubation with opossum kidney and Z310 rat choroid
      plexus cells, which express KL endogenously. All compounds elevated KL protein
      compared with control. To determine whether increased protein resulted in an in
      vitro functional change, we assayed FGF23 (fibroblast growth factor 23)
      signalling. Compounds G-I augmented ERK (extracellular-signal-regulated kinase)
      phosphorylation in FGFR (fibroblast growth factor receptor)-transfected cells,
      whereas co-transfection with KL siRNA (small interfering RNA) blocked the effect.
      These compounds will be useful tools to allow insight into the mechanisms of KL
      regulation. Further optimization will provide pharmacological tools for in vivo
      studies of KL.

PMID- 21939437
TI  - Cytoprotective effect of trolox against oxidative damage and apoptosis in the NRK
      52e cells induced by melamine.
AB  - An outbreak of urinary stones associated with consumption of melamine-tainted
      milk products occurred in 2008 in China, leading to serious illness of many
      infants and even death. However, the toxicity of melamine in kidney epithelial
      cells remains unclear. We have explored the effects of melamine and trolox on
      renal NRK-52e (normal rat kidney 52e) cells. The IC(50) of melamine was measured
      by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay.
      Total SOD (superoxide dismutase) was determined by NBT (Nitro Blue Tetrazolium)
      staining method. GSH-Px (glutathione peroxidase) activity was detected by UV
      colorimetric assay, and MDA (malondialdehyde) content was determined by
      thiobarbituric acid assay. Apoptosis induced by melamine was determined by flow
      cytometry. The IC(50) increased when NRK-52e cells were treated with both
      melamine and trolox compared with melamine only. SOD and GSH-Px activities were
      decreased, but MDA content was increased by melamine in a dose-dependent manner.
      Trolox significantly enhanced SOD and GSH-Px activity in melamine-treated NRK-52e
      cells, but it decreased their MDA content. LDH (lactate dehydrogenase) activity
      and the level of ROS (reactive oxygen species) of the NRK-52e cells were enhanced
      by melamine compared with the control. Furthermore, the apoptosis rate increased
      in NRK-52e cells treated with melamine, whereas trolox was protective. These
      results show that melamine has an obvious adverse effect on proliferation of NRK
      52e cells, causing oxidative damage and apoptosis, thus providing a novel insight
      into renal cytotoxicology of melamine. Trolox ameliorates the effect on melamine
      toxicity.

PMID- 21939438
TI  - Behavioural resistance against a protozoan parasite in the monarch butterfly.
AB  - 1. As parasites can dramatically reduce the fitness of their hosts, there should
      be strong selection for hosts to evolve and maintain defence mechanisms against
      their parasites. One way in which hosts may protect themselves against parasitism
      is through altered behaviours, but such defences have been much less studied than
      other forms of parasite resistance. 2. We studied whether monarch butterflies
      (Danaus plexippus L.) use altered behaviours to protect themselves and their
      offspring against the protozoan parasite Ophryocystis elektroscirrha (McLaughlin
      & Myers (1970), Journal of Protozoology, 17, p. 300). In particular, we studied
      whether (i) monarch larvae can avoid contact with infectious parasite spores;
      (ii) infected larvae preferentially consume therapeutic food plants when given a
      choice or increase the intake of such plants in the absence of choice; and (iii)
      infected female butterflies preferentially lay their eggs on medicinal plants
      that make their offspring less sick. 3. We found that monarch larvae were unable
      to avoid infectious parasite spores. Larvae were also not able to preferentially
      feed on therapeutic food plants or increase the ingestion of such plants.
      However, infected female butterflies preferentially laid their eggs on food
      plants that reduce parasite growth in their offspring. 4. Our results suggest
      that animals may use altered behaviours as a protection against parasites and
      that such behaviours may be limited to a single stage in the host-parasite life
      cycle. Our results also suggest that animals may use altered behaviours to
      protect their offspring instead of themselves. Thus, our study indicates that an
      inclusive fitness approach should be adopted to study behavioural defences
      against parasites.

PMID- 21939439
TI  - Performance evaluation and optimization of multiplex PCRs for the highly
      discriminating OSU 10-locus set Y-STRs.
AB  - In a previous study, a new set of Y-chromosome short tandem repeats, the OSU 10
      locus set (MPM1 and MPM2), was shown to have a higher discrimination power when
      evaluated against the 10 SWGDAM loci on a common population panel. Here, we
      describe the optimization of the multiplex reactions using dye-labeled primers
      followed by performance evaluations. The loci exhibited high precision, human
      male specificity, reliability in different body fluids, high sensitivity,
      stability, and the ability to amplify nonprobative casework and mixture samples.
      Stutter for the all of the loci, with the exception of the highly polymorphic
      locus DYS688, was similar to that observed for autosomal loci. The results of the
      performance evaluations reinforced the utility of these loci.

PMID- 21939440
TI  - Evaluating the demographic buffering hypothesis with vital rates estimated for
      Weddell seals from 30 years of mark-recapture data.
AB  - 1. Life-history theory predicts that those vital rates that make larger
      contributions to population growth rate ought to be more strongly buffered
      against environmental variability than are those that are less important. Despite
      the importance of the theory for predicting demographic responses to changes in
      the environment, it is not yet known how pervasive demographic buffering is in
      animal populations because the validity of most existing studies has been called
      into question because of methodological deficiencies. 2. We tested for
      demographic buffering in the southern-most breeding mammal population in the
      world using data collected from 5558 known-age female Weddell seals over 30
      years. We first estimated all vital rates simultaneously with mark-recapture
      analysis and then estimated process variance and covariance in those rates using
      a hierarchical Bayesian approach. We next calculated the population growth rate's
      sensitivity to changes in each of the vital rates and tested for evidence of
      demographic buffering by comparing properly scaled values of sensitivity and
      process variance in vital rates. 3. We found evidence of positive process
      covariance between vital rates, which indicates that all vital rates are affected
      in the same direction by changes in annual environment. Despite the positive
      correlations, we found strong evidence that demographic buffering occurred
      through reductions in variation in the vital rates to which population growth
      rate was most sensitive. Process variation in vital rates was inversely related
      to sensitivity measures such that variation was greatest in breeding
      probabilities, intermediate for survival rates of young animals and lowest for
      survival rates of older animals. 4. Our work contributes to a small but growing
      set of studies that have used rigorous methods on long-term, detailed data to
      investigate demographic responses to environmental variation. The information
      from these studies improves our understanding of life-history evolution in
      stochastic environments and provides useful information for predicting population
      responses to future environmental change. Our results for an Antarctic apex
      predator also provide useful baselines from a marine ecosystem when its top- and
      middle-trophic levels were not substantially impacted by human activity.

PMID- 21939441
TI  - The use of a 3-D laser scanner to document ephemeral evidence at crime scenes and
      postmortem examinations.
AB  - Proper documentation of physical evidence at both crimes scenes and postmortem
      examination is crucial for downstream analysis, interpretation, and presentation
      in court. Ephemeral or transient evidence poses particular challenges to
      investigators, as its very nature renders it difficult or impossible to seize and
      maintain in its original physical state. The use of a hand-held three-dimensional
      (3-D) laser scanner is proposed to capture and document such evidence, both in
      the field and at autopsy. Advantages of the scanner over traditional means of
      documentation such as photography or casting include the ability to obtain
      measurements in all dimensions, the ability to reconstruct missing elements, and
      the ease with which generated images can be interpreted by the jury at trial.
      Potential scenarios warranting the use of the scanner are identified, and the
      limitations of its use are discussed.

PMID- 21939442
TI  - Watch for those fragments of evidence: the use of an automatic timepiece to help
      correlate a helicopter crash site from the Vietnam War.
AB  - This case study illustrates the use of the date function on an automatic
      wristwatch to help identify a Vietnam War helicopter crash site. The location of
      a crash incident can sometimes be uncertain because of inadequate or inaccurate
      wartime records and the passage of time. Artifacts recovered from a prospective
      crash scene are regularly used to correlate the loss incident. In this case
      study, a recovered automatic watch displayed a date 2 days later than the
      reported loss incident. Although the date conflicts with the aircraft crash
      incident report, it is observed that a fully wound automatic watch continues to
      work for c. 2 days after movement of the watch ceases. Thus, the watch's date in
      fact correlates with the aircraft crash incident report. It is noted that
      automatic watches may also be used to date scenes of crime.

PMID- 21939443
TI  - Determination of sex from juvenile crania by means of discriminant function
      analysis.
AB  - This study provides evidence of craniofacial growth variation between the sexes
      in juveniles of European descent. Data were collected from lateral cephalometric
      radiographs belonging to the Michigan Craniofacial Growth Study. The collection
      consists of longitudinal lateral radiographs that represent individuals 5-16
      years of age. Each radiograph was manually traced on hyprint vellum from which
      eight craniometric points were identified. From these points, 20 craniofacial
      measurements were recorded and then analyzed by means of a canonical discriminant
      function analysis. Sex classification equations were then created by applying a
      backward stepwise procedure to the discriminant functions. The analysis
      demonstrates the presence of sexually dimorphic differences in craniofacial
      growth. The neurocranium is the most sexually dimorphic region of the juvenile
      craniofacial skeleton, until the onset of puberty. Size is the main source of
      variation with males having taller and longer heads than females. Overall, sex
      classification in the sample ranges from 78 to 89% accuracy.

PMID- 21939444
TI  - Psychological autopsy in the investigation of serial neonaticides.
AB  - While the use of psychological autopsies has at least a 50-year history in the
      investigation of equivocal deaths and suicides, we report a case where, after the
      discovery of a woman who died of natural causes, a subsequent search of her home
      found three deceased newborn infants. The infants were born on three separate
      occasions; the most recent was delivered approximately 2 weeks before the death
      of the mother. Using her own diaries and interviews with family and friends along
      with the physical autopsy and scene investigation data, we built a psychological
      autopsy that addressed the mother's mental state over the period of time when the
      infants' deaths took place. While the use of the psychological autopsy was not
      employed to distinguish the manner of death of the mother, it did provide
      explanatory power over circumstances of the crime scene and the behavioral
      disturbance of the mother.

PMID- 21939445
TI  - Could shading reduce the negative impacts of drought on coffee? A
      morphophysiological analysis.
AB  - Based on indirect evidence, it was previously suggested that shading could
      attenuate the negative impacts of drought on coffee (Coffea arabica), a tropical
      crop species native to shady environments. A variety (47) of morphological and
      physiological traits were examined in plants grown in 30-l pots in either full
      sunlight or 85% shade for 8 months, after which a 4-month water shortage was
      implemented. Overall, the traits showed weak or negligible responses to the light
      * water interaction, explaining less than 10% of the total data variation. Only
      slight variations in biomass allocation were observed in the combined shade and
      drought treatment. Differences in relative growth rates were mainly associated
      with physiological and not with morphological adjustments. In high light, drought
      constrained the photosynthetic rate through stomatal limitations with no sign of
      apparent photoinhibition; in low light, such constraints were apparently linked
      to biochemical factors. Sun-grown plants displayed osmotic adjustments, decreased
      tissue elasticities and improved long-term water use efficiencies, especially
      under drought. Regardless of the water availability, higher concentrations of
      lipids, total phenols, total soluble sugars and lignin were found in high light
      compared to shade conditions, in contrast to the effects on cellulose and
      hemicellulose concentrations. Proline concentrations increased in water-deprived
      plants, particularly those grown under full sun. Phenotypic plasticity was much
      higher in response to the light than to the water supply. Overall, shading did
      not alleviate the negative impacts of drought on the coffee tree.

PMID- 21939446
TI  - Natural variation and persistent developmental instabilities in geographically
      diverse accessions of the allopolyploid Arabidopsis suecica.
AB  - Allopolyploids arise from the hybridization of two species concomitant to genome
      doubling. While established allopolyploids are common in nature and vigorous in
      growth, early generation allopolyploids are often less fertile than their
      progenitors and display frequent phenotypic instabilities. It is commonly assumed
      that new allopolyploid species must pass through a bottleneck from which only
      those lines emerge that have reconciled genomic incompatibilities inherited from
      their progenitors in their combined genome, yet little is known about the
      processes following allopolyploidization over evolutionary time. To address the
      question if a single allopolyploidization event leads to a single new homogeneous
      species or may result in diverse offspring lines, we have investigated 13 natural
      accessions of Arabidopsis suecica, a relatively recent allopolyploid derived from
      a single hybridization event. The studied accessions display low genetic
      diversity between lines, yet show evidence of heritable phenotypic diversity of
      traits, some of which may be adaptive. Furthermore, our data show that contrary
      to the notion that unstable phenotypes in neoallopolyploids are eliminated
      rapidly in the new species, some instabilities are carried along throughout the
      species' evolution, persisting in the established allopolyploid. In summary, our
      results suggest that a single allopolyploidization event may lay the foundation
      for diverse populations of the new allopolyploid species.

PMID- 21939447
TI  - Rewarding development of teaching skills and educational scholarship.

PMID- 21939448
TI  - Changing conversations, changing culture: a medical education journal club.

PMID- 21939449
TI  - Social media in medical education: two innovative pilot studies.

PMID- 21939450
TI  - Changing medical students' attitudes about ageing and health.

PMID- 21939451
TI  - Impact of epidemiological and statistical skills training in undergraduates.

PMID- 21939452
TI  - Financial literacy for the graduating medical student.

PMID- 21939453
TI  - Human, sexual and reproductive rights in health care.

PMID- 21939454
TI  - Aldolase mRNA expression in endometrial cancer and the role of clotrimazole in
      endometrial cancer cell viability and morphology.

PMID- 21939455
TI  - Blastic plasmacytoid dendritic cell neoplasm presenting as a renal mass.

PMID- 21939456
TI  - An easy cell counting method for immunohistochemistry that does not use an image
      analysis program.

PMID- 21939457
TI  - Spherule-like acellular stroma in clear cell carcinoma of the ovary: its utility
      in frozen section diagnosis.

PMID- 21939458
TI  - Effect of prolonged formalin fixation on immunohistochemical staining for the
      proliferation marker Ki67.

PMID- 21939460
TI  - National Institute for Health and Clinical Excellence (NICE) guideline: psychosis
      with coexisting substance misuse.

PMID- 21939459
TI  - Increased p38 mitogen-activated protein kinase signaling is involved in the
      oxidative stress associated with oxygen and glucose deprivation in neonatal
      hippocampal slice cultures.
AB  - The pathological basis of neonatal hypoxia-ischemia (HI) brain damage is
      characterized by neuronal cell loss. Oxidative stress is thought to be one of the
      main causes of HI-induced neuronal cell death. The p38 mitogen-activated protein
      kinase (MAPK) is activated under conditions of cell stress. However, its
      pathogenic role in regulating the oxidative stress associated with HI injury in
      the brain is not well understood. Thus, this study was conducted to examine the
      role of p38 MAPK signaling in neonatal HI brain injury using neonatal rat
      hippocampal slice cultures exposed to oxygen/glucose deprivation (OGD). Our
      results indicate that OGD led to a transient increase in p38 MAPK activation that
      preceded increases in superoxide generation and neuronal death. This increase in
      neuronal cell death correlated with an increase in the activation of caspase-3
      and the appearance of apoptotic neuronal cells. Pre-treatment of slice cultures
      with the p38 MAPK inhibitor, SB203580, or the expression of an antisense p38 MAPK
      construct only in neuronal cells, through a Synapsin I-1-driven adeno-associated
      virus vector, inhibited p38 MAPK activity and exerted a neuroprotective effect as
      demonstrated by decreases in OGD-mediated oxidative stress, caspase activation
      and neuronal cell death. Thus, we conclude that the activation of p38 MAPK in
      neuronal cells plays a key role in the oxidative stress and neuronal cell death
      associated with OGD.

PMID- 21939461
TI  - The relationship between childhood depressive symptoms and problem alcohol use in
      early adolescence: findings from a large longitudinal population-based study.
AB  - AIMS: Depressive symptomatology can increase risk of development of alcohol
      problems in young people. Tension reduction and family interactional theories may
      explain the relationship between depression and problematic alcohol use in youth.
      This study addresses the nature of the longitudinal relationship between these
      two behaviours. The available literature is currently inconclusive about whether
      there are gender differences in these relationships; this is also examined.
      DESIGN: The association between childhood depressive behaviours and adolescence
      problematic alcohol use was examined using ordered logistic regression models.
      Evidence of gender differences and the impact of relevant covariates on these
      relations were examined. Missing data were imputed using a Multiple Imputation by
      Chained Equation (MICE) approach. SETTINGS: The Avon Longitudinal Study of
      Parents and Children (ALSPAC), a large UK population-based birth cohort.
      PARTICIPANTS: A total of 4220 British boys and girls. MEASUREMENTS: Depressive
      symptomatology was assessed in childhood (mean age = 10.6, SD = 0.2) using the
      Short Mood and Feelings Questionnaire (SMFQ). Problematic alcohol use was
      assessed from several questions queried in adolescence (mean age = 13.8, SD =
      0.2). FINDINGS: Childhood depressive symptoms were associated with increased risk
      of problematic alcohol use in early adolescence for girls [odds ratio (OR) =
      1.14, P = 0.016] but not boys. This association for girls weakened (OR = 1.12, P
      = 0.058) when a priori selected covariates were taken into account, particularly
      the family and greater social environment. CONCLUSIONS: Problematic alcohol use
      in girls (but not boys) is associated with prior depressive symptoms. This
      association may be attributable to several family and social environment factors,
      suggesting that a family interactional theoretical model may explain these
      findings.

PMID- 21939462
TI  - Impact of in-patient research participation on subsequent heroin use patterns:
      implications for ethics and public health.
AB  - AIMS: Research on drug dependence often involves the administration of drugs of
      abuse to experienced drug users under controlled laboratory conditions. The
      primary objective of this study was to assess whether participation in such
      research alters the frequency of heroin use by non-treatment-seeking opioid
      dependent volunteers after study completion. DESIGN: Data were examined from four
      in-patient studies involving controlled opioid administration. SETTING: Substance
      Use Research Center at Columbia University, New York State Psychiatric Institute.
      PARTICIPANTS: Sixty-nine heroin-dependent volunteers. MEASUREMENTS: Participants'
      self-reported heroin use prior to and 1 month after study participation was
      compared using a Wilcoxon test. Because a number of participants reported that
      they had stopped using heroin, a logistic regression was used to identify
      correlates of heroin cessation 1 month after study completion. FINDINGS: One
      hundred and one participants entered laboratory studies and 69 completed them.
      Self-reported heroin use significantly decreased 1 month after study
      participation [1.7 (+/-2.0) bags per day] compared to baseline [6.8 (+/-4.2) bags
      per day], P < 0.001 among the 69 completers. In addition, 42% of the completers
      were heroin-abstinent 1 month after study completion. Being African American,
      having a history of opioid dependence treatment, reporting heavier heroin use at
      baseline and a longer history of heroin use were correlated with cessation of
      heroin use. CONCLUSIONS: Participation in opioid administration studies does not
      increase subsequent heroin use and for some individuals leads to accessing opioid
      dependence treatment and cessation of heroin use in the short term.

PMID- 21939464
TI  - Natural selection. II. Developmental variability and evolutionary rate.
AB  - In classical evolutionary theory, genetic variation provides the source of
      heritable phenotypic variation on which natural selection acts. Against this
      classical view, several theories have emphasized that developmental variability
      and learning enhance nonheritable phenotypic variation, which in turn can
      accelerate evolutionary response. In this paper, I show how developmental
      variability alters evolutionary dynamics by smoothing the landscape that relates
      genotype to fitness. In a fitness landscape with multiple peaks and valleys,
      developmental variability can smooth the landscape to provide a directly
      increasing path of fitness to the highest peak. Developmental variability also
      allows initial survival of a genotype in response to novel or extreme
      environmental challenge, providing an opportunity for subsequent adaptation. This
      initial survival advantage arises from the way in which developmental variability
      smooths and broadens the fitness landscape. Ultimately, the synergism between
      developmental processes and genetic variation sets evolutionary rate.

PMID- 21939463
TI  - A longitudinal study of substance use and violent victimization in adulthood
      among a cohort of urban African Americans.
AB  - AIMS: This paper examines the effects of experiencing violent victimization in
      young adulthood on pathways of substance use from adolescence to mid-adulthood.
      DESIGN: Data come from four assessments of an African American community cohort
      followed longitudinally from age 6 to 42 years. SETTING: The cohort lived in the
      urban, disadvantaged Woodlawn neighborhood of Chicago in 1966. PARTICIPANTS: All
      first graders from the public and parochial schools were asked to participate (n
      = 1242). MEASUREMENT: Dependent variables-alcohol, marijuana and cocaine use-came
      from self-reports at age 42. Young adult violent victimization was reported at
      age 32, as were acts of violence, substance use, social integration and socio
      economic resources. First grade risk factors came from mothers' and teachers'
      reports; adolescent substance use was self-reported. FINDINGS: Structural
      equation models indicate a pathway from adolescent substance use to young adult
      violent victimization for females and those who did not grow up in extreme
      poverty (betas ranging from 0.15 to 0.20, P < 0.05). In turn, experiencing
      violent victimization in young adulthood increased alcohol, marijuana and cocaine
      use, yet results varied by gender and early poverty status (betas ranging from
      0.12 to 0.15, P < 0.05). CONCLUSIONS: Violent victimization appears to play an
      important role in perpetuating substance use among the African American
      population. However, within-group variations are evident, identifying those who
      are not raised in extreme poverty as the most negatively affected by violence.

PMID- 21939465
TI  - Natural selection. I. Variable environments and uncertain returns on investment.
AB  - Many studies have analysed how variability in reproductive success affects
      fitness. However, each study tends to focus on a particular problem, leaving
      unclear the overall structure of variability in populations. This fractured
      conceptual framework often causes particular applications to be incomplete or
      improperly analysed. In this article, I present a concise introduction to the two
      key aspects of the theory. First, all measures of fitness ultimately arise from
      the relative comparison of the reproductive success of individuals or genotypes
      with the average reproductive success in the population. That relative measure
      creates a diminishing relation between reproductive success and fitness.
      Diminishing returns reduce fitness in proportion to variability in reproductive
      success. The relative measurement of success also induces a frequency dependence
      that favours rare types. Second, variability in populations has a hierarchical
      structure. Variable success in different traits of an individual affects that
      individual's variation in reproduction. Correlation between different
      individuals' reproduction affects variation in the aggregate success of
      particular alleles across the population. One must consider the hierarchical
      structure of variability in relation to different consequences of temporal,
      spatial and developmental variability. Although a complete analysis of
      variability has many separate parts, this simple framework allows one to see the
      structure of the whole and to place particular problems in their proper relation
      to the general theory. The biological understanding of relative success and the
      hierarchical structure of variability in populations may also contribute to a
      deeper economic theory of returns under uncertainty.

PMID- 21939466
TI  - Unraveling the glioma epigenome: from molecular mechanisms to novel biomarkers
      and therapeutic targets.
AB  - Epigenetic regulation of gene expression by DNA methylation and histone
      modification is frequently altered in human cancers including gliomas, the most
      common primary brain tumors. In diffuse astrocytic and oligodendroglial gliomas,
      epigenetic changes often present as aberrant hypermethylation of 5'-cytosine
      guanine (CpG)-rich regulatory sequences in a large variety of genes, a phenomenon
      referred to as glioma CpG island methylator phenotype (G-CIMP). G-CIMP is
      particularly common but not restricted to gliomas with isocitrate dehydrogenase 1
      (IDH1) or 2 (IDH2) mutation. Recent studies provided a mechanistic link between
      these genetic mutations and the associated widespread epigenetic modifications.
      Specifically, 2-hydroxyglutarate, the oncometabolite produced by mutant IDH1 and
      IDH2 proteins, has been shown to function as a competitive inhibitor of various
      alpha-ketoglutarate (alpha-KG)-dependent dioxygenases, including histone
      demethylases and members of the ten-eleven-translocation (TET) family of 5
      methylcytosine (5mC) hydroxylases. In this review article, we briefly address (i)
      the basic principles of epigenetic control of gene expression; (ii) the most
      important methods to analyze focal and global epigenetic alterations in cells and
      tissues; and (iii) the involvement of epigenetic alterations in the molecular
      pathogenesis of gliomas. Moreover, we discuss the promising roles of epigenetic
      alterations as molecular diagnostic markers and novel therapeutic targets, and
      highlight future perspectives toward unraveling the "glioma epigenome."

PMID- 21939468
TI  - Colonization and infection by colistin-resistant Gram-negative bacteria in a
      cohort of critically ill patients.
AB  - In recent years there has been renewed interest in colistin for the treatment of
      infections by multidrug-resistant Gram-negative bacteria, causing concern that
      increasing use may be accompanied by the emergence of resistance. This is a
      retrospective cohort study of colonization and infection by colistin-resistant
      (CR) gram-negative bacteria in critically ill patients. Colonization data were
      based on surveillance culture results. Among 150 patients, 78 (52%) were
      colonized by CR Gram-negative bacteria. Among them, 30 (20%) were colonized by
      Klebsiella pneumoniae isolates and 51 (34%) were colonized by intrinsically
      resistant to colistin (CIR) enterobacteriaceae. Seven cases of infection were
      caused by CR K. pneumoniae and 12 cases by CIR strains. The main risk factor for
      colonization by CR pathogens was colistin treatment.

PMID- 21939467
TI  - Deep brain stimulation for early-stage Parkinson's disease: an illustrative case.
AB  - OBJECTIVES: Subthalamic nucleus (STN) deep brain stimulation (DBS) is an
      effective intervention in advanced Parkinson's disease (PD), but its efficacy and
      safety in early PD are unknown. We are conducting a randomized pilot trial
      investigating DBS in early PD. This report describes one participant who received
      bilateral STN-DBS. MATERIALS AND METHODS: Thirty subjects have been randomized to
      either optimal drug therapy (ODT) or DBS + ODT. Microelectrode recordings from
      the STN and substantia nigra are collected at implantation. The Unified
      Parkinson's Disease Rating Scale Motor Subscale (UPDRS-III) is administered in
      the ON and OFF states semi-annually and neuropsychological function and quality
      of life are assessed annually. We describe a 54-year-old man with a two-year
      history of PD who was randomized to DBS + ODT and followed for two years.
      RESULTS: The subject showed a lower STN to substantia nigra ratio of neuronal
      activity than advanced PD patients, and higher firing rate than non-PD patients.
      The subject's total UPDRS and UPDRS-III scores improved during the two-year
      follow-up, while his OFF UPDRS-III score and levodopa equivalent daily dose
      increased. Quality of life, verbal fluency, and verbal learning improved. He did
      not experience any serious adverse events. CONCLUSIONS: This report details the
      first successful application of bilateral STN-DBS for early-stage PD during a
      clinical trial.

PMID- 21939469
TI  - Survival of hepatitis A and E viruses in soil samples.
AB  - Survival of hepatitis A virus (HAV) and hepatitis E virus (HEV) in soil samples
      spiked with respective viruses was analysed using real-time PCR. Virus-spiked
      soil samples were incubated at environmental temperature (ET) and 37 degrees C
      and processed weekly. Both HAV and HEV were less stable at fluctuating ET than at
      37 degrees C. Of the 403 soil samples collected in the vicinity of Mutha river,
      India, 19.1% and 4.9% were found to be contaminated with HAV and HEV,
      respectively.

PMID- 21939470
TI  - Characterization of Acinetobacter baumannii from intensive care units and home
      care patients in Palermo, Italy.
AB  - In this study 45 isolates of Acinetobacter baumannii identified from patients in
      intensive care units of three different hospitals and from pressure ulcers in
      home care patients in Palermo, Italy, during a 3-month period in 2010, were
      characterized. All isolates were resistant to at least three classes of
      antibiotics, but susceptible to colistin and tygecycline. Forty isolates were non
      susceptible to carbapenems. Eighteen and two isolates, respectively, carried the
      bla(OXA-23-like) and the bla(OXA-58-like) genes. One strain carried the VIM-4
      gene. Six major rep-PCR subtype clusters were defined, including isolates from
      different hospitals or home care patients. The sequence type/pulsed field gel
      electrophoresis group ST2/A included 33 isolates, and ST78/B the remaining 12.
      ST2 clone proved to be predominant, but a frequent involvement of the ST78 clone
      was evident.

PMID- 21939471
TI  - Oropharyngeal yeast colonization in HIV-infected outpatients in southern Taiwan:
      CD4 count, efavirenz therapy and intravenous drug use matter.
AB  - To understand the status of oropharyngeal yeast colonization in human
      immunodeficiency virus (HIV) -infected outpatients in the era of highly active
      antiretroviral therapy (HAART), we conducted a prospective, cross-sectional study
      from October 2009 to January 2010 at a medical centre in southern Taiwan. Fungal
      cultures of the oropharyngeal swabs were performed on 327 enrolled patients. At
      enrolment, 258 (79%) patients had been receiving HAART, and 42 (12.8%), 73
      (22.3%) and 212 (64.8%) patients had CD4 cell counts <=200, 201-350, and >350
      cells/mm(3) , respectively. Oral yeast colonization was detected in 193 (59%)
      patients, among whom 157 (81.3%), 25 (13.0%), and 11 (5.7%) were colonized by a
      single, two and more than two species, respectively. Multivariate analysis showed
      that receipt of efavirenz-containing regiments and CD4 cell counts >200
      cells/mm(3) were associated with lower risks of oral yeast colonization, while
      intravenous drug users were at a higher risk. Among the 241 isolates recovered,
      Candida albicans accounted for 69.7%, followed by C. dubliniensis (9.5%), C.
      glabrata (8.3%), C. tropicalis (3.3%), C. intermedia (2.1%), C. parapsilosis
      (1.7%), and 11 other species (5.4%). Overall, 230 (95.4%), 236 (97.9%) and 240
      (99.6%) isolates were susceptible to fluconazole, voriconazole and amphotericin
      B, respectively. In conclusion, colonization by C. dubliniensis has emerged in
      recent years. In addition to a CD4 cell count <=200 cells/mm(3) , which is a
      known risk factor for oropharyngeal yeast colonization in HIV-infected patients
      that was identified in our previous studies, two risk factors, non-receipt of
      efavirenz-based combinations and intravenous drug use, were first identified in
      the present study. Fluconazole remained effective in vitro against the yeasts
      colonizing the oropharynx in this population.

PMID- 21939473
TI  - Are we losing the fight against malaria one more time?

PMID- 21939472
TI  - Emergence of carbapenem-resistant Enterobacteriaceae in Austria, 2001-2010.
AB  - We report the emergence of carbapenem-resistant Enterobacteriaceae in Austria.
      Over a 10-year period, carbapenem-resistant Enterobacteriaceae isolates were
      obtained from 13 hospitalized patients, with the first isolation in the year 2005
      and a remarkable increase in the number of involved patients in 2010. Carbapenem
      resistant Enterobacteriaceae comprise eight Klebsiella pneumoniae isolates, four
      Klebsiella oxytoca isolates, and one Escherichia coli isolate. The detected
      carbapenemases were the metallo-beta-lactamases New Delhi beta-lactamase, VIM and
      IMP, and the serin-beta-lactamase Klebsiella pneumoniae carbapenemase.

PMID- 21939474
TI  - Nursing science and practical wisdom: the pillars of nursing knowledge.

PMID- 21939475
TI  - The top eight issues Queensland Australia's aged-care nurses and assistants-in
      nursing worried about outside their workplace: a qualitative snapshot.
AB  - The attainment of a work-life balance is an important issue for recruitment,
      retention and workforce planning. This paper aims to report on the free text data
      provided by the aged-care sector nurses around perceptions of important work-life
      issues. Data were written responses of aged-care nurses to the open-ended request
      at the end of a survey, which asked them to list up to five
      political/social/environmental issues concerning them outside of their work. For
      aged-care nurses, when asked to list political/social/environmental issues they
      were concerned about outside of work in late 2007, there emerged considered
      issues around work and life. Among the top eight themes there is an intriguing
      balance between the themes work, industrial relations, aged care/elder care and
      health-care services compared with the themes environment, water, societal values
      and housing. Qualitative insights into the political/social/environmental issues
      aged-care nurses are concerned about outside of your work suggest their desire
      for a labour/life or work/life harmony. Aged-care nurses place an equal
      importance on the nature of labour and the basics of life. The findings provide
      information for aged-care sector managers and workforce planners on areas in need
      of consideration to recruit and retain a workforce within aged care.

PMID- 21939476
TI  - Factors affecting evidence translation for general practice nurses.
AB  - This paper explores the domains of influence affecting practice nurses' ability
      to find, evaluate and use clinical evidence. A cross-sectional survey of general
      practice nurses (n = 590) in Victoria, Australia in 2008 provided data for a
      principal components analysis. The research replicates a study undertaken in the
      UK using the Developing Evidence-Based Practice Questionnaire. Five domains of
      influence on nurses' translation of evidence were identified: skills in
      finding/reviewing evidence; barriers to finding/reviewing evidence; knowledge
      from published sources; knowledge from other sources; and barriers or
      facilitators to change. Each domain was interpreted as underlying the
      relationship of nurses with evidence-based practice and was comparable to the
      original study's findings when subjected to factor analysis. Findings from this
      study show that the Developing Evidence-Based Practice Questionnaire-Au is a
      valid and useful instrument in determining the influences on practice nurses'
      ability to effect knowledge translation and conduct practice based on evidence.
      Given these findings, a new model is proposed that explains the influence of a
      number of domains on Australian general practice nurses' translation of knowledge
      into practice.

PMID- 21939477
TI  - Hand-washing behaviour and nurses' knowledge after a training programme.
AB  - The aim of this study was to evaluate the nurses' hand-washing behaviour and
      knowledge before and after a training programme. This prospective study involved
      200 nurses who participated in hand-washing training at a university hospital in
      Turkey. The data were collected using a personal information form and pre- and
      post-test surveys that had been developed by the researchers. During the study,
      the nurses received 40 min of training on hand washing and a handbook prepared by
      the researchers. The hand-washing behaviour and knowledge of the nurses were
      assessed before training and 1 month after the training. To analyse the data,
      descriptive statistics, a t-test and a Mc Nemar chi-squared test were used.
      Following the training, there was a significant increase in the frequency of hand
      washing by the nurses (t = -2.202, P = 0.029), together with an increase in the
      time allowed for hand washing (P = 0.024, P < 0.05), knowledge of hand-washing
      practices (t = -16.081, P < 0.05) and quality (t = -10.874, P < 0.05). Planned
      training programmes for hand washing should be implemented to improve the
      behaviour and knowledge of nurses.

PMID- 21939478
TI  - Behaviour-change interventions in primary care: influence on nutrition and on the
      metabolic syndrome definers.
AB  - The purpose of this paper was to examine whether interventions influenced
      patients' (i) consumption of fish; whole grain products; fruits and vegetables;
      (ii) overall nutrition, that is, the three former as an index; and (iii) clinical
      outcomes in terms of metabolic syndrome definers. A questionnaire was delivered
      to adult patients entering the nine health centres on November 2006 (n = 1211).
      During the year the ward personnel conducted intervention on patients with
      unhealthy habits. The 12-month follow up was conducted by mailings. Also clinical
      data of pre- and post-intervention values of metabolic syndrome definers were
      collected. For the analyses, intervention was divided into brief (<= 15 min, at
      most three visits) and extended (> 15 min, more than three visits) intervention.
      Logistic Regression and manova were used to measure changes in the outcomes.
      Nutrition-related intervention was conducted on 218 patients (brief intervention
      n = 179, extended intervention n = 39). In the extended intervention group it was
      three times more likely to have a positive change in the nutrition index than in
      the brief intervention group (P = 0.017, confidence interval 1.223-7.773). In
      conclusion, brief interventions were commonly used in the primary care. However,
      they were not enough to produce changes in the patients' nutrition or in the
      clinical outcomes.

PMID- 21939479
TI  - Relationships in pain: the experience of relationships to people living with
      chronic pain in rural areas.
AB  - The aim of the study was to develop new understanding of the lived experience of
      relationships for rural people living with chronic pain. Rural residents have
      greater difficulty accessing health services and providers. This is especially
      important to those living with chronic pain who often find themselves isolated
      from professionals who could potentially offer support. A phenomenological study
      with seven participants who had experienced chronic non-malignant pain for 2-29
      years (Mean = 13) was recruited via a number of approaches and data analyzed
      using van Manen's framework. The themes that emerged from the analysis were as
      follows: pain as silence; privacy as a way of protection; no place out here to
      get support; and dealing with health-care professionals who do not understand.
      Lack of specialist services and support in rural areas means people with chronic
      pain are placed in even more vulnerable situations. Nurses remain at the
      forefront of service delivery in rural areas; hence, their role in management of
      people with chronic pain is vital in supporting them to maintain meaningful
      contact with others, including health professionals.

PMID- 21939480
TI  - Nursing and midwifery college students' expectations of their educators and
      perceived stressors during their education: a pilot study in Turkey.
AB  - Nursing and midwifery education is known to be negatively affected by several
      factors. Nevertheless, the present learning environments for students can be
      effectively altered to optimize their learning and practical training and
      decrease their stress levels. In order to minimize the stressors and to encourage
      the qualities needed of a competent educator, it would be important to first
      determine students' perceived stressors and the expectations they have of their
      educators. The main purpose of the study was to define the expectations that
      nursing and midwifery college students have of their educators as well as the
      stressors they perceive during their education. The present descriptive study was
      carried out with 474 students; there were 345 nursing students and 129 midwifery
      students at a college in northeastern Turkey. Data were obtained with a
      questionnaire and assessed with X(2) analyses. The findings of the study
      demonstrated that a majority of the students had some expectations of the
      educators and perceived stressors during their education. The students' most
      common expectations of the educators included their desire to be understood
      during their clinical education. In addition, students wanted the educators to
      make more use of visual materials during the theoretical part of their courses.
      The study also determined that the students felt very stressed when they were
      questioned by the educator on both clinical and theoretical aspects of their
      coursework.

PMID- 21939481
TI  - Perception of patient aggression among nurses working in a university hospital in
      Turkey.
AB  - The way patient aggression is perceived influences nurses' attitudes and
      behaviour towards patients. The aim of this cross-sectional, descriptive study
      was to investigate how nurses working in a university hospital perceive
      aggression and whether certain variables (sociodemographic and professional
      characteristics, exposure to aggressive behaviour) affect that perception. Two
      hundred and eighteen nurses (response rate 68.1%) from different departments were
      administered the Perception of Aggression Scale, a self-reported scale measuring
      perception of patient aggression towards nurses. The nurses in this study
      generally perceived patient aggression as dysfunctional. Nurses exposed to
      patient aggression in their professional lives regarded patient aggression more
      as dysfunctional. In addition, the oldest nurses, the most professionally
      experienced and those with the longest tenure in their departments had less
      perception of aggression as functional than others. Professional fatigue and burn
      out might play a role in this.

PMID- 21939482
TI  - Nursing diagnoses in patients having mechanical ventilation support in a
      respiratory intensive care unit in Turkey.
AB  - This research was carried out to find out the nursing diagnoses in patients who
      have mechanical ventilation support in a respiratory intensive care unit. The
      study was conducted with 51 evaluations of critically ill adult patients who
      underwent invasive and non-invasive mechanical ventilation therapy in 2008. Data
      collection was based on Gordon's 11 Functional Health Patterns, and nursing
      diagnoses were determined according to North American Nursing Diagnosis
      Association-International (NANDA-I) Taxonomy II. The nursing diagnoses were
      determined by two researchers separately. The consistency between the nursing
      diagnoses defined by the two researchers was evaluated by using Cohen's kappa
      (kappa). Forty men (78.4%) and 11 women (21.6%) whose mean ages were 70.19 (SD =
      8.96) years were included in the study. Nineteen subgroups of nursing diagnoses
      about safety/protection domain, and 15 subgroups about activity/rest domain were
      seen at different rates in the patients. There was a statistically significant
      difference between mechanical ventilation via tracheostomy or endotracheal tube
      and decreased cardiac output (d.f. = 1, chi(2) = 4.760, P = 0.029). The
      relationship between the length of time under mechanical ventilation and impaired
      physical mobility was considerably significant (d.f. = 3, chi(2) = 24.459, P =
      0.000). It was found out that there was a high degree of agreement (96.8%)
      between the nursing diagnoses defined by the two researchers separately (kappa =
      0.936, SE = 0.08).

PMID- 21939483
TI  - Building organizational capacity for effective mentorship of pre-registration
      nursing students during placement learning: Finnish and British mentors'
      conceptions.
AB  - Health-care organizations have a key role in improving the quality of student
      mentorship in placements. This study presents the findings of Finnish and British
      mentors' conceptions of how to build organizational capacity for the provision of
      effective mentorship for pre-registration nursing students during placement
      learning. The data obtained from nine semistructured focus group interviews were
      analyzed using a phenomenographic approach. Three categories of description are
      presented. Organizations were mainly perceived as optimizers of investments in
      developing clear strategies for the provision of sufficient resources and
      professional support for mentors. The creation of a positive mentorship culture
      within a development-oriented, student-centred and goal-directive atmosphere was
      seen as essential. Furthermore, providing well-prepared placements for clinical
      practice of students was emerged as crucial, which included adequate working
      conditions and stakeholders as well as arrangements of learning opportunities. It
      is concluded that effective student mentorship requires health-care organizations
      to invest in financial and human resources in order to promote the quality of the
      placement learning environments. Such provision will enhance students'
      recruitment, retention and effectiveness, leading to safe practice and cost
      benefits for health-care organizations in the longer term.

PMID- 21939484
TI  - Development of the Attitude Scale for Nursing Profession.
AB  - There is a need to have an appropriate instrument to measure the attitudes
      towards nursing profession. This study was carried out to develop an Attitude
      Scale for Nursing Profession (ASNP). The population of the study is composed of
      final-year students of high schools, the patients, the nurses and students of
      nursing department. A total of 600 participants were included in this study. The
      people in the sampling group were asked to write a composition containing their
      feelings and thoughts about nursing. These compositions were analysed and 89
      items about positive and negative attitude were determined. These items were
      presented to expert opinion and after necessary editions, reliability and
      validity analyses were conducted. The resulting ASNP consists of 40 items across
      the following three domains: properties of nursing profession prefer to nursing
      profession, general position of nursing profession. The final model in
      confirmatory factor analysis showed that this 40-item ASNP indicated a good fit
      of the model. The value of the Cronbach's alpha for the total scale was 0.91. The
      ASNP is determined to be quite highly valid and reliable, sufficient measuring
      instrument to determine attitude towards the profession.

PMID- 21939485
TI  - The inaccuracy of automatic devices taking postural measurements in the emergency
      department.
AB  - Automatic devices are used to take postural blood pressures in the emergency
      department despite research proving their inaccuracy in taking single blood
      pressures. This study assessed the accuracy of an automatic device compared with
      a manual aneroid reference standard for determining orthostatic hypotension and
      postural drops at triage. Supine and standing blood pressures were taken with an
      automatic and a manual device in a sequential and random order, and postural
      drops were calculated. The manual device indicated 10/150 emergency department
      patients had orthostatic hypotension (7%) and the automatic device detected this
      with a sensitivity of 30% and a specificity of 91%. The automatic-manual
      differences were clinically significant in 13% of systolic drops and 37% of
      diastolic drops. Findings suggest that automatic devices cannot reliably detect
      or rule out orthostatic hypotension, indicating that triage nurses need to use
      manual devices to take accurate postural blood pressures for optimal patient
      care.

PMID- 21939486
TI  - Tobacco and media exposure in poor neighbourhoods: implications for the incidence
      of smoking among community residents.
AB  - It is an accepted truth that tobacco, as well as second-hand smoke, causes lung
      and other cancers. This health policy fact sheet examines the need and
      implications for tobacco control legislation in the United States. Major
      stakeholders and special interest groups influence whether or not further tobacco
      control legislation can be passed and who it affects. This paper will review not
      only the ethical implications, such as the ethical theory, ethical principles and
      ethical rules of conduct that support tobacco control legislation, but also its
      legal and economic implications as well as media influences. This paper concludes
      with the authors' assessment that the United States is in fact in need of more
      tobacco control legislation.

PMID- 21939488
TI  - Characteristics and clinical significance of prostate cancers missed by initial
      transrectal 12-core biopsy.
AB  - OBJECTIVE: * To characterize prostate cancers missed by initial transrectal 12
      core biopsy. PATIENTS AND METHODS: * Between 2002 and 2008, 715 men with prostate
      specific antigen levels in the range 2.5-20 ng/mL or abnormal digital rectal
      examination underwent three-dimensional 26-core prostate biopsy (i.e. a
      combination of transrectal 12-core biopsy and transperineal 14-core biopsy) on
      initial examination. * Of the 257 patients diagnosed with cancer, 120 patients
      subsequently underwent radical prostatectomy. * Cancers were grouped into TR12
      negative cancers (i.e. not detected through transrectal 12-core biopsy but
      detected through transperineal 14-core biopsy) and TR12-positive (i.e. detected
      through transrectal 12-core biopsy) cancers. * Clinicopathological
      characteristics of the TR12-negative and TR12-positive cancers were evaluated.
      RESULTS: * TR12-negative cancers comprised 21% of the three-dimensional 26-core
      biopsy-detected cancers. * The frequency of cancers with a biopsy Gleason score
      <= 6 and that of cancers with a biopsy primary Gleason grade <= 3 was higher in
      TR12-negative cancers, at 58% and 83%, respectively, than in TR12-positive
      cancers, at 25% (P < 0.001) and 53% (P < 0.001), respectively. * The median
      number of positive cores in TR12-negative cancers was two out of 26. * TR12
      negative cancers were more frequently located anteriorly than posteriorly. * The
      incidence of the TR12-negative cancers was not associated significantly with any
      clinical variable. CONCLUSION: * Many of the cancers missed by initial
      transrectal 12-core biopsy are probably low-grade and low-volume diseases,
      although initial transrectal 12-core biopsy has a small but definite risk of
      missing anterior significant cancers.

PMID- 21939487
TI  - Functional analysis of interaction sites on the N-terminal domain of clathrin
      heavy chain.
AB  - In clathrin-mediated membrane traffic, clathrin does not bind directly to cargo
      and instead binds to adaptors that mediate this function. For endocytosis, the
      main adaptor is the adaptor protein (AP)-2 complex, but it is uncertain how
      clathrin contacts AP-2. Here we tested in human cells the importance of the three
      binding sites that have been identified so far on the N-terminal domain (NTD) of
      clathrin. We find that mutation of each of the three sites on the NTD, alone or
      in combination, does not block clathrin/AP-2-mediated endocytosis in the same way
      as deletion of the NTD. We report here the fourth and final site on the NTD that
      is required for clathrin/AP-2-mediated endocytic function. Each of the four
      interaction sites can operate alone to mediate endocytosis. The observed
      functional redundancy between interaction sites on the NTD explains how
      productivity of clathrin-coated vesicle formation is ensured.

PMID- 21939489
TI  - Is robotic technology facilitating the minimally invasive approach to partial
      nephrectomy?
AB  - OBJECTIVE: * To establish its current status, this study reviews the literature,
      and reports developments in robotic-assisted partial nephrectomy (RPN),
      highlighting results from various studies that investigate the oncological and
      functional efficacy of RPN. Partial nephrectomy has become the standard therapy
      for the management of small renal masses. In an effort to overcome the
      perioperative morbidity associated with an open approach, and the extended warm
      ischaemia times associated with a laparoscopic approach, robotic platforms have
      been introduced. PATIENTS AND METHODS: * A search of Medline, EMBASE and Cochrane
      library databases was completed in July 2010 and used to identify pertinent
      original articles, editorials, comments and reviews, using the search term
      'partial nephrectomy'. Links to related references were surveyed, and all
      articles finally included were based on relevance and importance of content, as
      determined by the authors. RESULTS: * The robotic platform may offer the solution
      to bridge the gap between open and laparoscopic approaches, achieving warm
      ischaemia times that consistently average 20 minutes, and providing similar
      oncological and functional results via a shorter learning curve. It offers
      cosmesis and convalescence equivalent to that from laparoscopic partial
      nephrectomy, but with potentially fewer postoperative complications. CONCLUSION:
      * In terms of oncological and functional outcomes, the early experiences of RPN
      in selected series of patients appear at least equivalent to open and
      laparoscopic partial nephrectomy series. Randomized comparisons between the
      approaches are lacking, as are longer-term follow-up data for the robotic
      technique and formal cost analysis; these will be necessary before RPN can
      replace open partial nephrectomy as the new standard for the management of small
      renal masses. Trends continue to emerge that highlight the advantage of using the
      robotic platform to achieve a minimally invasive approach for partial
      nephrectomy, and with time and increasing expertise, this may become further
      apparent.

PMID- 21939490
TI  - Contrast-enhanced ultrasonography with contrast-tuned imaging technology for the
      detection of prostate cancer: comparison with conventional ultrasonography.
AB  - Study Type - Diagnostic (exploratory cohort) Level of Evidence 2b What's known on
      the subject? and What does the study add? The present study was to perform
      contrast-tuned imaging (CnTI) technology to detect prostate cancer and compare
      the use of CnTI technology for the detection of prostate cancer with conventional
      ultrasonography. The preliminary data from our study suggested that targeted
      biopsy of the prostate with CnTI technology could improve the cancer detection
      and detect higher grade prostate cancers. OBJECTIVES: To perform contrast
      enhanced ultrasonography (CEUS) using contrast-tuned imaging (CnTI) technology to
      detect prostate cancer. To evaluate the detection of prostate cancer with CnTI
      compared with conventional grey-scale and power Doppler ultrasonography. PATIENTS
      AND METHODS: In all, 150 patients referred for prostate biopsy were evaluated
      using transrectal grey-scale, power Doppler and CnTI ultrasonography. Biopsy was
      performed at 10 sites in each patient. If an abnormality was found at any of
      these three ultrasonography examinations, a biopsy specimen was targeted towards
      from the corresponding site. The performances of the three ultrasonography
      techniques for prostate cancer detection were compared. RESULTS: Prostate cancer
      was detected at 383 sites from 73 patients. The combination of these three
      examinations detected more patients with prostate cancer than grey-scale (P=
      0.002), power Doppler (P= 0.001) or baseline imaging (the combination of grey
      scale and power Doppler; P= 0.031) alone. By biopsy site, CnTI had higher
      sensitivity and accuracy (73.1% and 83.7%) than grey-scale (50.9%; P < 0.001 and
      78.8%; P < 0.001) or power Doppler (48.3%; P < 0.001 and 77.7%; P < 0.001), while
      the specificity was similar for grey-scale (88.4%), power Doppler (87.8%) and
      CnTI (87.3%; P > 0.05 in each case). CnTI had higher sensitivity (73.1% vs 62.9%;
      P < 0.001), specificity (87.3% vs 82.1%; P < 0.001) and accuracy (83.7% vs 77.2%;
      P < 0.001) than baseline imaging. The mean Gleason score of CnTI-positive cases
      was significantly higher than CnTI-negative cases (7.1 vs 6.3; P= 0.002).
      CONCLUSIONS: CEUS using CnTI technology enables a visualization of the
      microvasculature associated with prostate cancer. CnTI technology could be used
      to guide biopsy and improve the detection rate of prostate cancer. CnTI
      technology was able to detect higher grade prostate cancers.

PMID- 21939491
TI  - Angiotensin II type 1 (AT-1) receptor inhibition partially prevents the
      urodynamic and detrusor changes associated with bladder outlet obstruction: a
      mouse model.
AB  - Study Type - Therapy (case control) Level of Evidence 3b What's known on the
      subject? and What does the study add? Angiotensin II is the main effector peptide
      in the bladder local renin-angiotensin system. This experiment demonstrates the
      role of this local renin-angiotensin system with respect to bladder outlet
      obstruction. OBJECTIVE: * To determine if treatment with an angiotensin II type 1
      (AT-1) receptor antagonist, losartan, can prevent the structural and functional
      changes that occur in a mouse model of bladder outlet obstruction (BOO).
      MATERIALS AND METHODS: * Twenty-four Balb/CAN mice underwent partial urethral
      obstruction for 6 weeks. * Twelve mice were given oral losartan (10 mg/kg/day),
      and 12 were not. Six mice served as unobstructed controls, and six unobstructed
      mice were given oral losartan (10 mg/kg/day) to determine the effect of
      angiotensin II inhibition on the normal bladder. * Bladder capacity (C), detrusor
      pressure during voiding (Pdet) and volume at first non-voiding contraction (NVC1)
      as a percentage of C were recorded after 6 weeks. * Bladders were stained with
      haematoxylin and eosin for measurement of detrusor muscular thickness, and graded
      as 1 = atrophy (<100 um thick), 2 = normal (100-200 um thick), 3 = hypertrophy
      (>200 um thick) compared with controls. RESULTS: * Compared with controls, BOO
      mice had greater C (153.5 +/- 20.9 vs 57.5 +/- 7.4 ul, P < 0.01), higher Pdet
      (28.8 +/- 2.1 vs 12.1 +/- 2.1 mm Hg), lower NVC1 (median = 24% vs 54% P= 0.03).
      BOO mice manifested greater bladder weight (93.2 +/- 11.7 mg vs 26.8 +/- 2.40 mg,
      P < 0.01) and greater detrusor muscle thickness (median 3 vs 2, P= 0.02). *
      Compared with untreated BOO mice, mice treated with losartan had greater mean C
      (248.8 +/- 28.6 vs 153.5 +/- 20.9 uL, P= 0.01), no significant change in mean
      Pdet (24.7 +/- 1.6 vs 28.8 +/- 2.1 mm Hg, P= 0.2) and a higher mean NVC1 (47% vs
      24%, P= 0.02). * Treatment with losartan mediated an insignificant reduction in
      mean bladder weight (68.1 +/- 9.1 mg vs 93.2 +/- 11.7 mg, P= 0.10), but a
      significant reduction in detrusor muscle thickness (median 2 vs 3, P= 0.02).
      Losartan did not mediate any significant structural or functional changes in the
      unobstructed mouse bladder. CONCLUSION: * In a mouse model of BOO, treatment with
      an AT-1 antagonist partially prevented the urodynamic and structural changes that
      otherwise occur with BOO.

PMID- 21939492
TI  - A comparative performance analysis of total prostate-specific antigen, percentage
      free prostate-specific antigen, prostate-specific antigen velocity and urinary
      prostate cancer gene 3 in the first, second and third repeat prostate biopsy.
AB  - Study Type - Diagnosis (exploratory cohort) Level of Evidence 2b What's known on
      the subject? and What does the study add? Risk factor assessment in the repeat
      biopsy setting is affected by a decreasing diagnostic accuracy of each single
      risk factor (e.g. DRE, tPSA, %fPSA, complexed PSA, PSA density or PSAV] with
      increasing number of prostate biopsy sessions. PCA3 shows impressive diagnostic
      performance in the initial and early repeat biopsy settings. In a head-to-head
      comparison we demonstrate the concept that the number of previous repeat biopsy
      session strongly influences performance characteristics of biopsy risk factors,
      including PCA3. While the novel diagnostic marker would have avoided a
      considerable number of unnecessary biopsies in the first repeat biopsy scenario,
      its effects dissipated at second and >= third repeat biopsies. OBJECTIVE: To
      compare the performance characteristics of prostate cancer risk factors such as
      total prostate-specific antigen (tPSA), percentage free PSA (%fPSA), PSA velocity
      (PSAV) and urinary prostate cancer gene 3 (PCA3) at first, second and >= third
      repeat biopsy session. PATIENTS AND METHODS: Patients (n= 127) aged <=70 years,
      with suspicious digital rectal examination (DRE) and/or persistently elevated age
      specific total PSA levels (2.5-6.5 ng/mL) and/or suspicious prior histology
      (atypical small acinar proliferations [ASAPs]>= two cores affected by high-grade
      prostatic intra-epithelial neoplasia [HGPIN]) undergoing either a first, second,
      or >= third repeat biopsy were investigated using a 12- or 24-core biopsy scheme.
      PSAV (>= three values collected over >=12 months) was calculated using the log
      slope method. PCA3 scores were assessed using the Progensa assay(r). After
      stratification according to the number of previous biopsies (first, second and >=
      third), calculation of specificity, positive and negative predictive values (PPV,
      NPV) and the proportion of avoided unnecessary repeat biopsies (PAB) compared
      with tPSA at fixed sensitivity thresholds (75, 85 and 95%) were performed.
      Finally, accuracy estimates (area under the curve [AUC]) were quantified for each
      repeat biopsy scenario. RESULTS: At repeat biopsy, overall prostate cancer (PCa)
      detection was 34.6%. At first repeat biopsy, PCA3 predicted PCa best (AUC = 0.80)
      and would have avoided 72.2% of repeat biopsies (75% sensitivity) compared with
      tPSA. At second repeat biopsy, %fPSA demonstrated the highest accuracy (AUC =
      0.82) and would have avoided 66.7% of repeat biopsies (75% sensitivity) compared
      with tPSA. At >= third repeat biopsy, again %fPSA demonstrated the highest
      accuracy (AUC = 0.70) and would have avoided 45.0% of repeat biopsies (75%
      sensitivity) compared with tPSA. The main limitation of our study resides in its
      small sample size. CONCLUSIONS: The findings of the present study promote the
      concept that the number of previous repeat biopsy sessions strongly influences
      the performance characteristics of biopsy risk factors. Total PSA was no
      significant risk factor in the entire analysis. By contrast, %fPSA performed best
      at second and >= third repeat biopsy. PSAV's diagnostic potential was reserved to
      patients at second and >= third repeat biopsy. Finally, PCA3 demonstrated the
      highest diagnostic accuracy and potential to reduce unnecessary biopsies at first
      repeat biopsy. However, this advantage dissipated at second and >= third repeat
      biopsy.

PMID- 21939493
TI  - Tumour size, tumour complexity, and surgical approach are associated with
      nephrectomy type in small renal cortical tumours treated electively.
AB  - Study Type - Therapy (case series) Level of Evidence 4 What's known on the
      subject? and What does the study add? Although the benefits of nephron-sparing
      renal cortical tumour treatments are now widely accepted and have robust data
      supporting their oncological efficacy, safety, and positive effect on medium- and
      long-term renal function, the decision to perform partial nephrectomy (PN)
      remains a complex interaction between several competing factors. Various patient
      factors, e.g. comorbid conditions, age, body habitus, patient preference, etc.
      may effect this decision. Then there are the preferences of the surgeon him- or
      herself, including faculty with different operative techniques and surgical
      approaches, which may lead to one treatment decision over another. Finally, the
      anatomy of the tumour itself, i.e. the complexity of the tumour within the kidney
      and anatomical relationships within the organ, is intuitively critical to a
      surgeon's assessment of resectability. There is very little published data
      indicating which of the multitude of clinical variables have the greatest impact
      on the decision to perform PN. Most previous investigations into the subject have
      focused on either imperative or relative indications for PN (i.e. solitary
      kidney, bilateral renal masses, and multifocal tumours) or have used maximal
      tumour diameter (i.e. tumour size) alone in their assessment of the clinical
      variables associated with PN use. OBJECTIVE: To identify preoperative variables
      associated with choice of partial nephrectomy (PN) vs radical nephrectomy (RN).
      PATIENTS AND METHODS: Between January 2004 and June 2008, 203 patients were
      treated for clinical T1a renal cortical tumours. Of these, 154 (75.8%) had all
      data available and form the analytic cohort. Patients were categorized into two
      groups, PN and RN, based on preoperative treatment plan. Patient-, procedure-,
      and tumour-related variables, together with tumour complexity (based on the
      R.E.N.A.L Nephrometry Score [RENAL-NS]) were evaluated for their association with
      planned PN vs RN. RESULTS: PN was planned in 120/154 patients (77.9%). Minimally
      invasive surgical approaches were planned in 66/154 cases overall (42.9%) and in
      40/120 PN cases (33.3%). On univariate analysis, lower American Society of
      Anesthesiologists (ASA) score, planned open approach, smaller tumour size, left
      sided tumour, and lower RENAL-NS were associated with planned PN. On multivariate
      analysis three factors remained independently associated with PN: tumour size
      (each 1 cm decrease in tumour size odds ratio [OR] 2.2, 95% confidence interval
      [CI] 1.2-4.0, P= 0.011), tumour complexity quantified by RENAL-NS (each 1 point
      decrease OR 2.4, 95% CI 1.5-3.7, P < 0.001), and planned open surgical approach
      (OR 7.3, 95% CI 2.2-25, P= 0.001). CONCLUSIONS: The decision to perform elective
      PN is based primarily on tumour anatomical features but is also associated with
      surgical approach. The RENAL-NS accurately predicts nephrectomy type in clinical
      T1a renal cortical tumours.

PMID- 21939494
TI  - Two novel SCN9A gene heterozygous mutations may cause partial deletion of pain
      perception.
AB  - OBJECTIVE: The physiological sensation of pain and rapid response to stimuli
      serve as an adaptive way to avoid harmful situations. Our purpose was to
      investigate why this protection disappears or almost disappears for patients with
      congenital indifference to pain (CIP). DESIGN: The study was designed as a case
      report by scanning the candidate genes within CIP patients. SETTING: The study
      was set at the Department of Anesthesiology, Tongji Hospital, Tongji Medical
      College, Huazhong University of Science and Technology, Wuhan, China. PATIENTS:
      We reported patients from two Chinese families that showed insensitivity to pain
      and were diagnosed with CIP by a neurologist. Different from recently reported
      studies, our patients were not entirely painless, but demonstrated little pain
      sensation from injuries. MEASURES: The measures made were novel mutations within
      SCN9A. RESULTS: Sequence analysis of candidate genes of two affected individuals
      identified two novel heterozygous mutations (M899I and M932L) in the SCN9A gene.
      Furthermore, a novel nonsynonymous single-nucleotide polymorphism (SNP) within
      the SCN9A gene was revealed in affected proband and several unaffected family
      members. This polymorphism (c. 3312G&T, which produces the amino acid
      substitution V1104L in human Nav1.7), is present in 6.5% of healthy Chinese.
      CONCLUSIONS: We speculate that the mutations may be the cause of partial deletion
      of pain perceptionin in our probands, and the novel polymorphism V1104L may have
      a predictive role in the pain sensation of healthy individuals.

PMID- 21939495
TI  - Pain and functional capacity in female fibromyalgia patients.
AB  - OBJECTIVE: To examine the association between pain and functional capacity
      levels. DESIGN: [corrected] Cross-sectional study. SETTING: University of
      Granada. SUBJECTS: One hundred twenty-three women with fibromyalgia (51.7 +/- 7.2
      years). OUTCOME MEASURES: We measured weight and height, and body mass index
      (BMI) was calculated. We assessed tender points by pressure pain and functional
      capacity by means of the 30-second chair stand, handgrip strength, chair sit and
      reach, back scratch, blind flamingo, 8-ft up and go and 6-minute walk tests.
      RESULTS: We observed an association of tender points count with the chair stand
      and 6-minute walk tests (r = -0.273, P = 0.004 and r = -0.183, P = 0.046,
      respectively). These associations became nonsignificant once the analyses were
      adjusted by weight or BMI. We observed an association of algometer score with the
      back scratch, chair stand, and 6-minute walk tests (r = 0.238, P = 0.009; r =
      0.363, P < 0.001; and r = 0.186, P = 0.043, respectively), which remained after
      adjusting for weight or BMI, except the association between algometer score and
      the 6-minute walk test that became nonsignificant once the analyses were adjusted
      by weight. Prevalence of overweight and obesity was 39.2 and 33.3%, respectively.
      CONCLUSIONS: There is an inverse association of tender points count with the
      chair stand and distance walked in the 6-minute walk tests, and a positive
      association of algometer score with the chair stand, distance walked in the 6
      minute walk and back scratch tests, yet, weight status seems to play a role in
      these associations.

PMID- 21939496
TI  - Increasing prevalence of chronic musculoskeletal complaints. A large 11-year
      follow-up in the general population (HUNT 2 and 3).
AB  - OBJECTIVES: To assess the prevalence of chronic musculoskeletal complaints (MSCs)
      in a large adult population, and to determine any changes in prevalence during an
      11-year period. METHODS: This study involved two large cross-sectional surveys
      (Helseundersokelsen i Nord-Trondelag [HUNT] 2 and 3) of inhabitants in Nord
      Trondelag county aged >=20 years performed in 1995-97 (N = 92,936) and 2006-08 (N
      = 94,194). Attendance rates were 70 and 42%, respectively. Respondents with
      chronic MSCs were identified through the screening question "Have you during the
      last year continuously for at least 3 months had pain and/or stiffness in muscles
      and joints?" The reliability of the screening question was evaluated in a random
      sample of participants (N = 563). RESULTS: The reliability of the screening
      question was good (kappa value 0.63, 95% confidence interval [CI] 0.53-0.73). In
      HUNT 3, 48% had chronic MSCs and 20% had chronic widespread MSCs. The age
      adjusted prevalence of chronic MSCs was higher (P < 0.001) in HUNT 3 (47.9%, 95%
      CI 47.6-48.2) compared with HUNT 2 (44.8%, 95% CI 44.5-45.2), evident for both
      genders, and most prominent in the age group 20-29 years. Chronic widespread MSCs
      were more common in HUNT 3 than in HUNT 2 among women (28.2 vs 26.0%, P < 0.001).
      Increased prevalence during the 11-year period was also found in supplementary
      analyses evaluating the influence of differences in participation rate.
      CONCLUSIONS: The prevalence of chronic MSCs and chronic widespread MSCs is high.
      The prevalence of chronic MSCs increased during the 11-year period. A nonresponse
      bias interfering with the comparisons over time could not completely be ruled
      out.

PMID- 21939497
TI  - Efficacy of outpatient ketamine infusions in refractory chronic pain syndromes: a
      5-year retrospective analysis.
AB  - OBJECTIVE: We evaluated whether outpatient intravenous ketamine infusions were
      satisfactory for pain relief in patients suffering from various chronic
      intractable pain syndromes. DESIGN: Retrospective chart review. SETTING AND
      PATIENTS: Following Institutional Review Board approval, we retrospectively
      analyzed our database for all ketamine infusions administered over 5 years from
      2004 to 2009. OUTCOME MEASURES:   Data reviewed included doses of intravenous
      ketamine, infusion duration, pain scores on visual analog scale (VAS) pre- and
      post-procedure, long-term pain relief, previous interventions, and side effects.
      All patients were pretreated with midazolam and ondansetron. RESULTS:   We
      identified 49 patients undergoing 369 outpatient ketamine infusions through
      retrospective analysis. We excluded 36 infusions because of missing data. Among
      our patients, 18 (37%) had a diagnosis of complex regional pain syndrome (CRPS).
      Of the remaining 31 (63%) patients, eight had refractory headaches and seven had
      severe back pain. All patients reported significant reduction in VAS score of 5.9
      (standard error [SE] 0.35). For patients with CRPS, reduction in VAS score was
      7.2 (SE 0.51, P < 0.001); for the others, the reduction was 5.1 (SE 0.40, P <
      0.001). The difference of 2.1 between groups was statistically significant (SE
      0.64, P = 0.002). In 29 patients, we recorded the duration of pain relief. Using
      the Bernoulli model, we found (90% confidence interval) that the probability of
      lasting pain relief in patients with refractory pain states was 59-85% (23-51%
      relief over 3 weeks). CONCLUSIONS: We conclude that in patients with severe
      refractory pain of multiple etiologies, subanesthetic ketamine infusions may
      improve VAS scores. In half of our patients, relief lasted for up to 3 weeks with
      minimal side effects.

PMID- 21939498
TI  - Self-mutilation in patients after nerve injury may not be due to deafferentation
      pain: a case report.
AB  - OBJECTIVE: Animals with transected nerves may develop self-mutilating behavior
      (autotomy) directed at the denervated body part. Autotomy is often thought to be
      a response to deafferentation pain produced by pathological changes in the dorsal
      horn, and self-mutilation after dorsal rhizotomy has consequently been used as an
      outcome measure for the investigation of chronic pain in animal models. A less
      recognized hypothesis suggests that autotomy is simply an animal's efforts to
      remove the useless part. We report a case of self-mutilation of the thumb and
      fingers in a patient with loss of all sensory modalities in the arm after
      brachial plexus avulsion. CONCLUSION: Asking the patient about the reasons for
      his self-mutilation provides insights into the cause of autotomy which cannot be
      established from animal studies. We suggest that autotomy may not be a result of
      chronic pain, and discuss the human experience and alternative underlying
      pathological processes.

PMID- 21939499
TI  - The effect of deep and slow breathing on pain perception, autonomic activity, and
      mood processing--an experimental study.
AB  - OBJECTIVE: Deep and slow breathing (DSB) techniques, as a component of various
      relaxation techniques, have been reported as complementary approaches in the
      treatment of chronic pain syndromes, but the relevance of relaxation for
      alleviating pain during a breathing intervention was not evaluated so far.
      METHODS: In order to disentangle the effects of relaxation and respiration, we
      investigated two different DSB techniques at the same respiration rates and
      depths on pain perception, autonomic activity, and mood in 16 healthy subjects.
      In the attentive DSB intervention, subjects were asked to breathe guided by a
      respiratory feedback task requiring a high degree of concentration and constant
      attention. In the relaxing DSB intervention, the subjects relaxed during the
      breathing training. The skin conductance levels, indicating sympathetic tone,
      were measured during the breathing maneuvers. Thermal detection and pain
      thresholds for cold and hot stimuli and profile of mood states were examined
      before and after the breathing sessions. RESULTS: The mean detection and pain
      thresholds showed a significant increase resulting from the relaxing DSB, whereas
      no significant changes of these thresholds were found associated with the
      attentive DSB. The mean skin conductance levels indicating sympathetic activity
      decreased significantly during the relaxing DSB intervention but not during the
      attentive DSB. Both breathing interventions showed similar reductions in negative
      feelings (tension, anger, and depression). CONCLUSION: Our results suggest that
      the way of breathing decisively influences autonomic and pain processing, thereby
      identifying DSB in concert with relaxation as the essential feature in the
      modulation of sympathetic arousal and pain perception.

PMID- 21939501
TI  - Compassionate use of dexamethasone implant for the treatment of macular edema
      secondary to central retinal vein occlusion in a clinical setting.

PMID- 21939500
TI  - Preliminary evidence of abnormal white matter related to the fusiform gyrus in
      Williams syndrome: a diffusion tensor imaging tractography study.
AB  - Williams syndrome (WS) is a genetic condition caused by a hemizygous
      microdeletion on chromosome 7q11.23. WS is characterized by a distinctive social
      phenotype composed of increased drive toward social engagement and attention
      toward faces. In addition, individuals with WS exhibit abnormal structure and
      function of brain regions important for the processing of faces such as the
      fusiform gyrus. This study was designed to investigate if white matter tracts
      related to the fusiform gyrus in WS exhibit abnormal structural integrity as
      compared to typically developing (TD; age matched) and developmentally delayed
      (DD; intelligence quotient matched) controls. Using diffusion tensor imaging data
      collected from 40 (20 WS, 10 TD and 10 DD) participants, white matter fibers were
      reconstructed that project through the fusiform gyrus and two control regions
      (caudate and the genu of the corpus callosum). Macro-structural integrity was
      assessed by calculating the total volume of reconstructed fibers and micro
      structural integrity was assessed by calculating fractional anisotropy (FA) and
      fiber density index (FDi) of reconstructed fibers. WS participants, as compared
      to controls, exhibited an increase in the volume of reconstructed fibers and an
      increase in FA and FDi for fibers projecting through the fusiform gyrus. No
      between-group differences were observed in the fibers that project through the
      control regions. Although preliminary, these results provide further evidence
      that the brain anatomy important for processing faces is abnormal in WS.

PMID- 21939502
TI  - Study rationale and design of OPTIMISE, a randomised controlled trial on the
      effect of benchmarking on quality of care in type 2 diabetes mellitus.
AB  - BACKGROUND: To investigate the effect of physician- and patient-specific feedback
      with benchmarking on the quality of care in adults with type 2 diabetes mellitus
      (T2DM). METHODS: Study centres in six European countries were randomised to
      either a benchmarking or control group. Physicians in both groups received
      feedback on modifiable outcome indicators (glycated haemoglobin [HbA1c],
      glycaemia, total cholesterol, high density lipoprotein-cholesterol, low density
      lipoprotein [LDL]-cholesterol and triglycerides) for each patient at 0, 4, 8 and
      12 months, based on the four times yearly control visits recommended by
      international guidelines. The benchmarking group also received comparative
      results on three critical quality indicators of vascular risk (HbA1c, LDL
      cholesterol and systolic blood pressure [SBP]), checked against the results of
      their colleagues from the same country, and versus pre-set targets. After 12
      months of follow up, the percentage of patients achieving the pre-determined
      targets for the three critical quality indicators will be assessed in the two
      groups. RESULTS: Recruitment was completed in December 2008 with 3994 evaluable
      patients. CONCLUSIONS: This paper discusses the study rationale and design of
      OPTIMISE, a randomised controlled study, that will help assess whether
      benchmarking is a useful clinical tool for improving outcomes in T2DM in primary
      care. TRIAL REGISTRATION: NCT00681850.

PMID- 21939503
TI  - Downregulation of E-Cadherin enhances proliferation of head and neck cancer
      through transcriptional regulation of EGFR.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) has been reported to
      downregulate E-cadherin (E-cad); however, whether the downregulation of E-cad has
      any effect on EGFR expression has not been elucidated. Our previous studies have
      found an inverse correlation between EGFR and E-cad expression in tissue
      specimens of squamous cell carcinoma of the head and neck (SCCHN). To understand
      the biological mechanisms underlying this clinical observation, we knocked down E
      cad expression utilizing E-cad siRNA in four SCCHN cell lines. RESULTS: It was
      observed that downregulation of E-cad upregulated EGFR expression compared with
      control siRNA-transfected cells after 72 hours. Cellular membrane localization of
      EGFR was also increased. Consequently, downstream signaling molecules of the EGFR
      signaling pathway, p-AKT, and p-ERK, were increased at 72 hours after the
      transfection with E-cad siRNA. Reverse transcriptase-polymerase chain reaction
      (RT-PCR) showed EGFR mRNA was upregulated by E-cad siRNA as early as 24 hours. In
      addition, RT-PCR revealed this upregulation was due to the increase of EGFR mRNA
      stability, but not protein stability. Sulforhodamine B (SRB) assay indicated
      growth of E-cad knocked down cells was enhanced up to 2-fold more than that of
      control siRNA-transfected cells at 72-hours post-transfection. The effect of E
      cad reduction on cell proliferation was blocked by treating the E-cad siRNA
      transfected cells with 1 MUM of the EGFR-specific tyrosine kinase inhibitor
      erlotinib. CONCLUSION: Our results suggest for the first time that reduction of E
      cad results in upregulation of EGFR transcriptionally. It also suggests that loss
      of E-cad may induce proliferation of SCCHN by activating EGFR and its downstream
      signaling pathways.

PMID- 21939505
TI  - Baseline results of the first malaria indicator survey in Iran at household
      level.
AB  - BACKGROUND: Malaria is one of the leading causes of sickness and death in the
      developing world, causing more than a million deaths and around 250 million new
      cases annually worldwide. The aim of this comprehensive survey was to provide
      information on malaria indicators at household level in high-risk malaria areas
      in Iran. METHODS: In a cluster randomized cross-sectional survey data were
      collected from 5,456 households in both rural and urban areas of 20 malaria
      affected districts of Iran. All the fieldwork was done by trained interviewers
      and a validated questionnaire. The questionnaire comprised baseline
      characteristics of the study population, the knowledge of people about different
      aspects of malaria (such as clinical symptoms, transmission and prevention) and
      their practice to prevent illness (such as using mosquito nets, spraying houses).
      The data were analysed and descriptive statistics (i.e. frequencies, percentages)
      were used to summarize the results. RESULTS: The results of this survey showed
      that 20% (95% CI: 17.36-22.24) of households owned at least one mosquito net,
      whether treated or untreated. Consequently, the use of mosquito nets was
      considerably low among both children under age five [5.90% (95% CI: 5.14-6.66)]
      and pregnant women [5.70% (95% CI: 3.07-8.33)]. Moreover, less than 10% of
      households reported that the interior walls of their dwelling had been sprayed in
      the previous year [8.70% (95% CI: 6.09-11.31)]. Data also suggest that 63.8% of
      the participants recognized fever as a sign of malaria, 56.4% reported that
      mosquito bites cause malaria and about 35% of participants mentioned that the use
      of mosquito nets could prevent malaria. CONCLUSION: Findings from this study
      indicate that low access to treated nets along with low understanding of the role
      of nets in malaria prevention are the main barriers to utilization of bed nets.
      Therefore, the use of insecticide-treated mosquito nets should be encouraged
      through health education on the importance of the use along with increasing
      access to it.

PMID- 21939504
TI  - Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs
      into breast cancer cells.
AB  - BACKGROUND: Tumor-associated macrophages (TAMs) are alternatively activated cells
      induced by interleukin-4 (IL-4)-releasing CD4+ T cells. TAMs promote breast
      cancer invasion and metastasis; however, the mechanisms underlying these
      interactions between macrophages and tumor cells that lead to cancer metastasis
      remain elusive. Previous studies have found microRNAs (miRNAs) circulating in the
      peripheral blood and have identified microvesicles, or exosomes, as mediators of
      cell-cell communication. Therefore, one alternative mechanism for the promotion
      of breast cancer cell invasion by TAMs may be through macrophage-secreted
      exosomes, which would deliver invasion-potentiating miRNAs to breast cancer
      cells. RESULTS: We utilized a co-culture system with IL-4-activated macrophages
      and breast cancer cells to verify that miRNAs are transported from macrophages to
      breast cancer cells. The shuttling of fluorescently-labeled exogenous miRNAs from
      IL-4-activated macrophages to co-cultivated breast cancer cells without direct
      cell-cell contact was observed. miR-223, a miRNA specific for IL-4-activated
      macrophages, was detected within the exosomes released by macrophages and was
      significantly elevated in the co-cultivated SKBR3 and MDA-MB-231 cells. The
      invasiveness of the co-cultivated breast cancer cells decreased when the IL-4
      activated macrophages were treated with a miR-223 antisense oligonucleotide (ASO)
      that would inhibit miR-223 expression. Furthermore, results from a functional
      assay revealed that miR-223 promoted the invasion of breast cancer cells via the
      Mef2c-beta-catenin pathway. CONCLUSIONS: We conclude that macrophages regulate
      the invasiveness of breast cancer cells through exosome-mediated delivery of
      oncogenic miRNAs. Our data provide insight into the mechanisms underlying the
      metastasis-promoting interactions between macrophages and breast cancer cells.

PMID- 21939506
TI  - The parasite clearance curve.
AB  - Parasite clearance rates are important measures of anti-malarial drug efficacy.
      They are particularly important in the assessment of artemisinin resistance. The
      slope of the log-linear segment in the middle of the parasite clearance curve has
      the least inter-individual variance and is the focus of therapeutic assessment.
      The factors affecting parasite clearance are reviewed. Methods of presentation
      and the approaches to analysis are discussed.

PMID- 21939507
TI  - Knowledge and malaria treatment practices using artemisinin combination therapy
      (ACT) in Malawi: survey of health professionals.
AB  - BACKGROUND: Malaria still remains a life-threatening disease worldwide causing
      between 190 and 311 million cases of malaria in 2008. Due to increased resistance
      to sulphadoxine-pyrimethamine (SP), the Ministry of Health in Malawi, as in many
      sub-Saharan African countries, changed the malaria treatment policy to use
      artemisinin-based combination therapy (ACT). In order to optimize the correct use
      of this drug, and protect against the development of the parasite's resistance,
      it is important to assess the knowledge and practices of medical practitioners on
      the use of ACT and its impact on adherence to new treatment policy guidelines.
      METHODS: A cross-sectional survey was conducted to assess the knowledge and
      perceptions of Malawian medical doctors and pharmacists on the use of ACT and the
      drivers of treatment choice and clinical treatment decisions. Medical doctors and
      pharmacists who are involved in managing malaria patients in Malawi were
      recruited and a self-administered questionnaire was used to obtain information on
      socio-demographic characteristics of the study participants, knowledge on ACT,
      source of information on ACT and methods used to decide on the treatment of
      patients with malaria. RESULTS: Most of the participants (95.7%) know at least
      one form of ACT, 67.4% reported that different forms of ACT have different
      characteristics, 77.3% reported that there are special formulations for children.
      The most commonly mentioned ACT was artemether-lumefantrine (AL), by 94.6% of the
      participants and 75.0% of the participants indicated that they prefer to
      prescribe AL. 73.9% of participants had ever received information on ACT.
      However, only 31.5% had received training on management of malaria using ACT.
      There were 71.7% respondents who had heard of ACT causing side effects. Only
      25.0% of the participants had received training on how to report SAEs.
      CONCLUSION: It was found that most of the participants know about ACT and
      treatment guidelines for malaria. However, most of the participants have not
      received any training on how to use ACT and how to report adverse effects arising
      from the use of ACT. There is need for more training of health care professionals
      to ensure correct and effective use of ACT.

PMID- 21939508
TI  - Effect of alpha(+)-thalassaemia on episodes of fever due to malaria and other
      causes: a community-based cohort study in Tanzania.
AB  - BACKGROUND: It is controversial to what degree alpha(+)-thalassaemia protects
      against episodes of uncomplicated malaria and febrile disease due to infections
      other than Plasmodium. METHODS: In Tanzania, in children aged 6-60 months and
      height-for-age z-score < -1.5 SD (n = 612), rates of fevers due to malaria and
      other causes were compared between those with heterozygous or homozygotes
      alpha(+)-thalassaemia and those with a normal genotype, using Cox regression
      models that accounted for multiple events per child. RESULTS: The overall
      incidence of malaria was 3.0/child-year (1, 572/526 child-years); no differences
      were found in malaria rates between genotypes (hazard ratios, 95% CI: 0.93, 0.82
      1.06 and 0.91, 0.73-1.14 for heterozygotes and homozygotes respectively, adjusted
      for baseline factors that were predictive for outcome). However, this association
      strongly depended on age: among children aged 6-17 months, those with alpha(+)
      thalassaemia experienced episodes more frequently than those with a normal
      genotype (1.30, 1.02-1.65 and 1.15, 0.80-1.65 for heterozygotes and homozygotes
      respectively), whereas among their peers aged 18-60 months, alpha(+)-thalassaemia
      protected against malaria (0.80, 0.68-0.95 and 0.78, 0.60-1.03; p-value for
      interaction 0.001 and 0.10 for hetero- and homozygotes respectively). No effect
      was observed on non-malarial febrile episodes. CONCLUSIONS: In this population,
      the association between alpha(+)-thalassaemia and malaria depends on age. Our
      data suggest that protection by alpha(+)-thalassaemia is conferred by more
      efficient acquisition of malaria-specific immunity.

PMID- 21939509
TI  - Identification of clinically significant psychological distress and psychiatric
      morbidity by examining quality of life in subjects with occupational asthma.
AB  - BACKGROUND: The Juniper Asthma Specific Quality of Life Questionnaire (AQLQ(S))
      is a questionnaire that allows measurement of disease specific quality of life.
      We wanted to examine correlations between the (AQLQ(S)) general and different
      subscale scores and both psychiatric morbidity and levels of psychological
      distress in individuals with occupational asthma (OA) and to determine if results
      in the emotional function subscale allow identification of individuals with
      clinically significant psychological distress or current psychiatric disorders.
      METHODS: This was a cross-sectional study of individuals with OA who were
      assessed during a re-evaluation for permanent disability, after they were no
      longer exposed to the sensitizing agent. Patients underwent a general
      sociodemographic and medical history evaluation, a brief psychiatric interview
      (Primary Care Evaluation of Mental Disorders, PRIME-MD) and completed a battery
      of questionnaires including the AQLQ(S), the St-Georges Respiratory Questionnaire
      (SGRQ), and the Psychiatric Symptom Index (PSI). RESULTS: There was good internal
      consistency (Cronbach alpha = 0.936 for the AQLQ(S) total score) and construct
      validity for the AQLQ(S) (Spearman rho = -0.693 for the SGRQ symptom score and
      rho = -0.650 for the asthma severity score). There were medium to large
      correlations between the total score of the AQLQ(S) and the SGRQ symptom score (r
      = -.693), and PSI total (r = -.619) and subscale scores (including depression, r
      = -.419; anxiety, r = -.664; anger, r = -.367; cognitive disturbances, r = 
      .419). A cut-off of 5.1 on the AQLQ(S) emotional function subscale (where 0 =
      high impairment and 7 = no impairment) had the best discriminative value to
      distinguish individuals with or without clinically significant psychiatric
      distress according to the PSI, and a cut-off of 4.7 best distinguished
      individuals with or without a current psychiatric disorder according to the PRIME
      MD. CONCLUSIONS: Impaired quality of life is associated with psychological
      distress and psychiatric disorders in individuals with OA. Findings suggest that
      the AQLQ(S) questionnaire may be used to identify patients with potentially
      clinically significant levels of psychological distress.

PMID- 21939510
TI  - Improvement in health-related quality of life after therapy with omeprazole in
      patients with coronary artery disease and recurrent angina-like chest pain. A
      double-blind, placebo-controlled trial of the SF-36 survey.
AB  - BACKGROUND: Many patients with coronary artery disease (CAD) have overlapping
      gastroenterological causes of recurrent chest pain, mainly due to
      gastroesophageal reflux (GER) and aspirin-induced gastrointestinal tract damage.
      These symptoms can be alleviated by proton pump inhibitors (PPIs). The study
      addressed whether omeprazole treatment also affects general health-related
      quality of life (HRQL) in patients with CAD. STUDY: 48 patients with more than
      50% narrowing of the coronary arteries on angiography without clinically overt
      gastrointestinal symptoms were studied. In a double-blind, placebo-controlled,
      cross-over study design, patients were randomized to take omeprazole 20 mg bid or
      a placebo for two weeks, and then crossed over to the other study arm. The SF-36
      questionnaire was completed before treatment and again after two weeks of
      therapy. RESULTS: Patients treated with omeprazole in comparison to the subjects
      taking the placebo had significantly greater values for the SF-36 survey (which
      relates to both physical and mental health), as well as for bodily pain, general
      health perception, and physical health. In comparison to the baseline values,
      therapy with omeprazole led to a significant increase in the three summarized
      health components: total SF-36; physical and mental health; and in the following
      detailed health concept scores: physical functioning, limitations due to physical
      health problems, bodily pain and emotional well-being. CONCLUSIONS: A double dose
      of omeprazole improved the general HRQL in patients with CAD without severe
      gastrointestinal symptoms more effectively than the placebo.

PMID- 21939511
TI  - Geographic distribution of need and access to health care in rural population: an
      ecological study in Iran.
AB  - INTRODUCTION: Equity in access to and utilization of health services is a common
      goal of policy-makers in most countries. The current study aimed to evaluate the
      distribution of need and access to health care services among Iran's rural
      population between 2006 and 2009. METHODS: Census data on population's
      characteristics in each province were obtained from the Statistical Centre of
      Iran and National Organization for civil registration. Data about the Rural
      Health Houses (RHHs) were obtained from the Ministry of Health. The Health Houses
      to-rural population ratio (RHP), crude birth rate (CBR) and crude mortality rate
      (CMR) in rural population were calculated in order to compare their distribution
      among the provinces. Lorenz curves of RHHs, CMR and CBR were plotted and their
      decile ratio, Gini Index and Index of Dissimilarity were calculated. Moreover,
      Spearman rank-order correlation was used to examine the relation between RHHs and
      CMR and CBR. RESULTS: There were substantial differences in RHHs, CMR and CBR
      across the provinces. CMR and CBR experienced changes toward more equal
      distributions between 2006 and 2009, while inverse trend was seen for RHHs.
      Excluding three provinces with markedly changes in data between 2006 and 2009 as
      outliers, did not change observed trends. Moreover; there was a significant
      positive relationship between CMR and RHP in 2009 and a significant negative
      association between CBR and RHP in 2006 and 2009. When three provinces with
      outliers were excluded, these significant associations were disappeared.
      CONCLUSION: Results showed that there were significant variations in the
      distribution of RHHs, CMR and CBR across the country. Moreover, the distribution
      of RHHs did not reflect the needs for health care in terms of CMR and CBR in the
      study period.

PMID- 21939512
TI  - Gold nanoparticles induced cloudy swelling to hydropic degeneration, cytoplasmic
      hyaline vacuolation, polymorphism, binucleation, karyopyknosis, karyolysis,
      karyorrhexis and necrosis in the liver.
AB  - BACKGROUND: Nanoparticles (NPs) can potentially cause adverse effects on organ,
      tissue, cellular, subcellular and protein levels due to their unusual
      physicochemical properties. Advances in nanotechnology have identified promising
      candidates for many biological and biomedical applications. The aim of the
      present study was to investigate the particle-size, dose and exposure duration
      effects of gold nanoparticles (GNPs) on the hepatic tissue in an attempt to cover
      and understand the toxicity and their potential therapeutic and diagnostic use.
      METHODS: A total of 70 healthy male Wistar-Kyoto rats were exposed to GNPs
      received 50 or 100 ul of GNPs infusion of size (10, 20 and 50 nm for 3 or 7 days)
      to investigate particle-size, dose and exposure duration effects of GNPs on the
      hepatic tissue. RESULTS: In comparison with respective control rats, exposure to
      GNPs doses has produced alterations in the hepatocytes, portal triads and the
      sinusoids. The alterations in the hepatocytes were mainly vacuolar to hydropic
      degeneration, cytopasmic hyaline vacuolation, polymorphism, binucleation,
      karyopyknosis, karyolysis, karyorrhexis and necrosis. CONCLUSIONS: The
      hepatocytes swelling might be exhibited as a result of disturbances of membranes
      function that lead to massive influx of water and Na+ due to GNPs effects
      accompanied by leakage of lysosomal hydrolytic enzymes that lead to cytoplasmic
      degeneration and macromolecular crowding. Hydropic degeneration is a result of
      ion and fluid homestasis that lead to an increase of intracellular water. The
      vacuolated swelling of the cytoplasm of the hepatocytes of the GNPs treated rats
      might indicate acute and subacute liver injury induced by the GNPs. Binucleation
      represents a consequence of cell injury and is a sort of chromosomes hyperplasia
      which is usually seen in regenerating cells. The induced histological alterations
      might be an indication of injured hepatocytes due to GNPs toxicity that became
      unable to deal with the accumulated residues resulting from metabolic and
      structural disturbances caused by these NPs. These alterations were size
      dependent with smaller ones induced the most effects and related with time
      exposure of GNPs. The appearance of hepatocytes cytoplasmic degeneration and
      nuclear destruction may suggest that GNPs interact with proteins and enzymes of
      the hepatic tissue interfering with the antioxidant defense mechanism and leading
      to reactive oxygen species (ROS) generation which in turn may induce stress in
      the hepatocytes to undergo atrophy and necrosis. More histomorphologcal,
      histochemical and ultrastrucural investigations are needed in relation of the
      application of GNPs with their potential role as a therapeutic and diagnostic
      tool.

PMID- 21939513
TI  - Analysis of the biofilm proteome of Xylella fastidiosa.
AB  - BACKGROUND: Xylella fastidiosa is limited to the xylem of the plant host and the
      foregut of insect vectors (sharpshooters). The mechanism of pathogenicity of this
      bacterium differs from other plant pathogens, since it does not present typical
      genes that confer specific interactions between plant and pathogens (avr and/or
      hrp). The bacterium is injected directly into the xylem vessels where it adheres
      and colonizes. The whole process leads to the formation of biofilms, which are
      considered the main mechanism of pathogenicity. Cells in biofilms are
      metabolically and phenotypically different from their planktonic condition. The
      mature biofilm stage (phase of higher cell density) presents high virulence and
      resistance to toxic substances such as antibiotics and detergents. Here we
      performed proteomic analysis of proteins expressed exclusively in the mature
      biofilm of X. fastidiosa strain 9a5c, in comparison to planktonic growth
      condition. RESULTS: We found a total of 456 proteins expressed in the biofilm
      condition, which correspond to approximately 10% of total protein in the genome.
      The biofilm showed 37% (or 144 proteins) different protein than we found in the
      planktonic growth condition. The large difference in protein pattern in the
      biofilm condition may be responsible for the physiological changes of the cells
      in the biofilm of X. fastidiosa. Mass spectrometry was used to identify these
      proteins, while real-time quantitative polymerase chain reaction monitored
      expression of genes encoding them. Most of proteins expressed in the mature
      biofilm growth were associated with metabolism, adhesion, pathogenicity and
      stress conditions. Even though the biofilm cells in this work were not submitted
      to any stress condition, some stress related proteins were expressed only in the
      biofilm condition, suggesting that the biofilm cells would constitutively express
      proteins in different adverse environments. CONCLUSIONS: We observed
      overexpression of proteins related to quorum sensing, proving the existence of
      communication between cells, and thus the development of structuring the biofilm
      (mature biofilm) leading to obstruction of vessels and development of disease.
      This paper reports a first proteomic analysis of mature biofilm of X. fastidiosa,
      opening new perspectives for understanding the biochemistry of mature biofilm
      growth in a plant pathogen.

PMID- 21939514
TI  - Calcium signaling around Mitochondria Associated Membranes (MAMs).
AB  - Calcium (Ca2+) homeostasis is fundamental for cell metabolism, proliferation,
      differentiation, and cell death. Elevation in intracellular Ca2+ concentration is
      dependent either on Ca2+ influx from the extracellular space through the plasma
      membrane, or on Ca2+ release from intracellular Ca2+ stores, such as the
      endoplasmic/sarcoplasmic reticulum (ER/SR). Mitochondria are also major
      components of calcium signalling, capable of modulating both the amplitude and
      the spatio-temporal patterns of Ca2+ signals. Recent studies revealed zones of
      close contact between the ER and mitochondria called MAMs (Mitochondria
      Associated Membranes) crucial for a correct communication between the two
      organelles, including the selective transmission of physiological and
      pathological Ca2+ signals from the ER to mitochondria. In this review, we
      summarize the most up-to-date findings on the modulation of intracellular Ca2+
      release and Ca2+ uptake mechanisms. We also explore the tight interplay between
      ER- and mitochondria-mediated Ca2+ signalling, covering the structural and
      molecular properties of the zones of close contact between these two networks.

PMID- 21939515
TI  - Abolished adherence alters signaling pathways in phorbol ester-induced human U937
      cells.
AB  - Phorbol ester (TPA) treatment of human U937 myeloid leukemia cells is associated
      with increasing adherence and monocyte-like maturation whereby the role of beta2
      integrin-mediated attachment for subsequent growth properties and the
      differentiation program remains unclear. Here, stably-transfected U937 cells with
      a pMTH1 vector containing the beta2 integrin gene of CD11b in antisense
      orientation (asCD11b-U937) demonstrated a significantly reduced proliferative
      capacity in contrast to control vector transfectants (pMTH1-U937) or wild-type
      U937 cells. Phorbol ester exposure induced adherence and growth arrest in more
      than 90% of pMTH1-U937 and wild-type U937 cells after 72 h. In contrast, TPA
      treated asCD11b-U937 failed to attach and the proliferation continued in more
      than 30% of the cells. Moreover, increased apoptosis appeared in asCD11b-U937
      after TPA induction in contrast to pMTH1-U937 cells. In addition, non-specific
      inhibition of adherence on an agarose surface demonstrated internucleosomal DNA
      fragmentation in both, pMTH1-U937 and asCD11b-U937 after TPA treatment indicating
      a functional relationship between abolished adherence, regulation of
      proliferation and induction of apoptosis. Western blot analysis revealed
      differences in the expression levels and altered phosphorylation patterns of Pyk
      2, pp60src and p42/p44 MAP kinases between pMTH1-U937 and asCD11b-U937 following
      TPA exposure which was also substantiated by Pyk-2 immunoprecipitation. These
      findings suggested that induced adherence predominantly mediated by a functional
      CD11b/CD18 integrin in U937 cells is involved in the activation of downstream
      signaling kinases and contributes to cell cycle regulation and apoptosis during
      monocytic maturation.

PMID- 21939516
TI  - Science under the lamppost.

PMID- 21939517
TI  - Overexpression of serine racemase in retina and overproduction of D-serine in
      eyes of streptozotocin-induced diabetic retinopathy.
AB  - BACKGROUND: Recent data indicate that inflammatory mechanisms contribute to
      diabetic retinopathy (DR). We have determined that serine racemase (SR)
      expression is increased by inflammatory stimuli including liposaccharide (LPS),
      amyloid beta-peptide (A-beta), and secreted amyloid precursor protein (sAPP);
      expression is decreased by the anti-inflammatory drug, dexamethasone. We tested
      possibility that SR and its product, D-serine, were altered in a rat model of DR.
      METHODS: Intraperitoneal injection of streptozotocin (STZ; 70 mg/kg body weight)
      to Sprague-Dawley rats produced type-I diabetic mellitus (fasting blood sugar
      higher than 300 mg/dL). At 3 and 5 months after STZ or saline injection, retinas
      from some rats were subjected to cryosectioning for immunofluorescent analysis of
      SR and TUNEL assay of apoptosis. Retinal homogenates were used to detect SR
      levels and Jun N-terminal kinase (JNK) activation by immunoblotting. Aqueous
      humor and retina were also collected to assay for neurotransmitters, including
      glutamate and D-serine, by reverse-phase HPLC. RESULTS: Compared to saline
      injected rats, STZ-injected (diabetic) rats showed elevation of SR protein levels
      in retinal homogenates, attributed to the inner nuclear layer (INL) by
      immunofluorescence. Aqueous humor fluid from STZ-injected rats contained
      significantly higher levels of glutamate and D-serine compared to controls; by
      contrast, D-serine levels in retinas did not differ. Levels of activated JNK were
      elevated in diabetic retinas compared to controls. CONCLUSIONS: Increased
      expression of SR in retina and higher levels of glutamate and D-serine in aqueous
      humor of STZ-treated rats may result from activation of the JNK pathway in
      diabetic sequelae. Our data suggest that the inflammatory conditions that prevail
      during DR result in elevation of D-serine, a neurotransmitter contributing to
      glutamate toxicity, potentially exacerbating the death of retinal ganglion cells
      in this condition.

PMID- 21939518
TI  - A network model for biofilm development in Escherichia coli K-12.
AB  - BACKGROUND: In nature, bacteria often exist as biofilms. Biofilms are communities
      of microorganisms attached to a surface. It is clear that biofilm-grown cells
      harbor properties remarkably distinct from planktonic cells. Biofilms frequently
      complicate treatments of infections by protecting bacteria from the immune
      system, decreasing antibiotic efficacy and dispersing planktonic cells to distant
      body sites. In this work, we employed enhanced Boolean algebra to model biofilm
      formation. RESULTS: The network obtained describes biofilm formation
      successfully, assuming - in accordance with the literature - that when the
      negative regulators (RscCD and EnvZ/OmpR) are off, the positive regulator (FlhDC)
      is on. The network was modeled under three different conditions through time with
      satisfactory outcomes. Each cluster was constructed using the K-means/medians
      Clustering Support algorithm on the basis of published Affymetrix microarray gene
      expression data from biofilm-forming bacteria and the planktonic state over four
      time points for Escherichia coli K-12. CONCLUSIONS: The different phenotypes
      obtained demonstrate that the network model of biofilm formation can simulate the
      formation or repression of biofilm efficiently in E. coli K-12.

PMID- 21939519
TI  - Attenuation of antigen-induced airway hyperresponsiveness and inflammation in
      CXCR3 knockout mice.
AB  - BACKGROUND: CD8+ T cells participate in airway hyperresponsiveness (AHR) and
      allergic pulmonary inflammation that are characteristics of asthma. CXCL10 by
      binding to CXCR3 expressed preferentially on activated CD8+ T cells, attracts T
      cells homing to the lung. We studied the contribution and limitation of CXCR3 to
      AHR and airway inflammation induced by ovalbumin (OVA) using CXCR3 knockout (KO)
      mice. METHODS: Mice were sensitized and challenged with OVA. Lung
      histopathological changes, AHR, cellular composition and levels of inflammatory
      mediators in bronchoalveolar lavage (BAL) fluid, and lungs at mRNA and protein
      levels, were compared between CXCR3 KO mice and wild type (WT) mice. RESULTS:
      Compared with the WT controls, CXCR3 KO mice showed less OVA-induced infiltration
      of inflammatory cells around airways and vessels, and less mucus production.
      CXCR3 KO mice failed to develop significant AHR. They also demonstrated
      significantly fewer CD8+ T and CD4+ T cells in BAL fluid, lower levels of
      TNFalpha and IL-4 in lung tissue measured by real-time RT-PCR and in BAL fluid by
      ELISA, with significant elevation of IFNgamma mRNA and protein expression levels.
      CONCLUSIONS: We conclude that CXCR3 is crucial for AHR and airway inflammation by
      promoting recruitment of more CD8+ T cells, as well as CD4+ T cells, and
      initiating release of proinflammatory mediators following OVA sensitization and
      challenge. CXCR3 may represent a novel therapeutic target for asthma.

PMID- 21939520
TI  - Network analysis of quantitative proteomics on asthmatic bronchi: effects of
      inhaled glucocorticoid treatment.
AB  - BACKGROUND: Proteomic studies of respiratory disorders have the potential to
      identify protein biomarkers for diagnosis and disease monitoring. Utilisation of
      sensitive quantitative proteomic methods creates opportunities to determine
      individual patient proteomes. The aim of the current study was to determine if
      quantitative proteomics of bronchial biopsies from asthmatics can distinguish
      relevant biological functions and whether inhaled glucocorticoid treatment
      affects these functions. METHODS: Endobronchial biopsies were taken from
      untreated asthmatic patients (n = 12) and healthy controls (n = 3). Asthmatic
      patients were randomised to double blind treatment with either placebo or
      budesonide (800 MUg daily for 3 months) and new biopsies were obtained. Proteins
      extracted from the biopsies were digested and analysed using isobaric tags for
      relative and absolute quantitation combined with a nanoLC-LTQ Orbitrap mass
      spectrometer. Spectra obtained were used to identify and quantify proteins.
      Pathways analysis was performed using Ingenuity Pathway Analysis to identify
      significant biological pathways in asthma and determine how the expression of
      these pathways was changed by treatment. RESULTS: More than 1800 proteins were
      identified and quantified in the bronchial biopsies of subjects. The pathway
      analysis revealed acute phase response signalling, cell-to-cell signalling and
      tissue development associations with proteins expressed in asthmatics compared to
      controls. The functions and pathways associated with placebo and budesonide
      treatment showed distinct differences, including the decreased association with
      acute phase proteins as a result of budesonide treatment compared to placebo.
      CONCLUSIONS: Proteomic analysis of bronchial biopsy material can be used to
      identify and quantify proteins using highly sensitive technologies, without the
      need for pooling of samples from several patients. Distinct pathophysiological
      features of asthma can be identified using this approach and the expression of
      these features is changed by inhaled glucocorticoid treatment. Quantitative
      proteomics may be applied to identify mechanisms of disease that may assist in
      the accurate and timely diagnosis of asthma. TRIAL REGISTRATION:
      ClinicalTrials.gov registration NCT01378039.

PMID- 21939521
TI  - Involvement of nitric oxide (NO) in cough reflex sensitivity between non
      sensitized and OVA-sensitized guinea pigs.
AB  - BACKGROUND: Exhaled nitric oxide (ENO) is elevated in bronchial asthma patients,
      and inhaled corticosteroid therapy lowers the elevated ENO levels in such
      patients. ENO appears to be an inflammatory marker, but its role in the
      pathophysiology of cough remains unclear. This study aimed to elucidate the
      relationship between NO and increased cough reflex sensitivity induced by
      allergic airway reactions. METHODS: Cough reflex sensitivity to inhaled capsaicin
      was observed under NO depletion caused by NO synthase (NOS) inhibitors in non
      sensitized and ovalbumin (OVA)-sensitized guinea pigs. The bronchoalveolar lavage
      fluid (BALF) was analyzed in an NO depletion setting using the inducible NOS
      (iNOS) inhibitor ONO1714 in OVA-sensitized guinea pigs. RESULTS: NO depletion by
      the non-selective NOS inhibitor L-NAME suppressed cough reflex sensitivity in non
      sensitized guinea pigs and OVA-induced increase in cough reflex sensitivity in
      sensitized guinea pigs; however, iNOS inhibition caused by ONO1714 partially
      suppressed the OVA-induced increase in cough reflex sensitivity, but not the
      normal cough response in non-sensitized guinea pigs. ONO1714 did not change BAL
      cell components in OVA-sensitized guinea pigs. CONCLUSIONS: The results suggest
      that NO may be involved not only in the normal cough reflex circuit, but also in
      the OVA-induced increase in cough reflex sensitivity, possibly via a different
      mechanism of action. Further studies are needed to clarify the precise mechanism.

PMID- 21939522
TI  - Folk medicine in the northern coast of Colombia: an overview.
AB  - BACKGROUND: Traditional remedies are an integral part of Colombian culture. Here
      we present the results of a three-year study of ethnopharmacology and folk
      medicine use among the population of the Atlantic Coast of Colombia, specifically
      in department of Bolivar. We collected information related to different herbal
      medicinal uses of the local flora in the treatment of the most common human
      diseases and health disorders in the area, and determined the relative importance
      of the species surveyed. METHODS: Data on the use of medicinal plants were
      collected using structured interviews and through observations and conversations
      with local communities. A total of 1225 participants were interviewed. RESULTS:
      Approximately 30 uses were reported for plants in traditional medicine. The plant
      species with the highest fidelity level (Fl) were Crescentia cujete L. (flu),
      Eucalyptus globulus Labill. (flu and cough), Euphorbia tithymaloides L.
      (inflammation), Gliricidia_sepium_(Jacq.) Kunth (pruritic ailments), Heliotropium
      indicum L. (intestinal parasites) Malachra alceifolia Jacq. (inflammation),
      Matricaria chamomilla L. (colic) Mentha sativa L. (nervousness), Momordica
      charantia L. (intestinal parasites), Origanum vulgare L. (earache), Plantago
      major L. (inflammation) and Terminalia catappa L. (inflammation). The most
      frequent ailments reported were skin affections, inflammation of the respiratory
      tract, and gastro-intestinal disorders. The majority of the remedies were
      prepared from freshly collected plant material from the wild and from a single
      species only. The preparation of remedies included boiling infusions, extraction
      of fresh or dry whole plants, leaves, flowers, roots, fruits, and seeds. The
      parts of the plants most frequently used were the leaves. In this study were
      identified 39 plant species, which belong to 26 families. There was a high degree
      of consensus from informants on the medical indications of the different species.
      CONCLUSIONS: This study presents new research efforts and perspectives on the
      search for new drugs based on local uses of medicinal plants. It also sheds light
      on the dependence of rural communities in Colombia on medicinal plants.

PMID- 21939523
TI  - Effect of a conventional energy-restricted modified diet with or without meal
      replacement on weight loss and cardiometabolic risk profile in overweight women.
AB  - BACKGROUND: Abdominal obesity, atherogenic dyslipidemia and hypertension are
      essential risk factors for cardiovascular diseases. Several studies showed
      favorable effects of weight loss in overweight subjects on cardiometabolic risk
      profile. METHODS: This open-label, randomized, controlled study investigated the
      effect of an energy-restricted modified diet with (MR) or without meal
      replacements for weight control (C) on weight loss, body composition and
      cardiometabolic risk profile in overweight women. Of 105 randomized participants,
      87 were eligible for per protocol analysis. Anthropometric, clinical, blood, 24 h
      urine parameters and dietary intake were assessed at baseline and after 12 weeks.
      RESULTS: Dietary intervention resulted in a significant weight loss in both
      groups (MR: -5.98 +/- 2.82 kg; p < 0.001, C: -4.84 +/- 3.54 kg; p < 0.001).
      However, the rate of responder (weight loss >5%) was higher in MR (77%) versus C
      group (50%) (p = 0.010). A significant reduction in waist circumference (WC) and
      body fat mass (BFM) was observed in both groups. Body cell mass (BCM) and lean
      body mass (LBM) decreased, while percentage of BCM of body weight increased in MR
      more than in C group. Systolic and diastolic blood pressure (BP) significantly
      decreased and to a similar extent in both groups. Total cholesterol (TC), LDL-C
      but also HDL-C declined significantly in both groups, while no change occurred in
      triglycerides. CONCLUSIONS: Both dietary intervention strategies had a similar
      effect on weight loss and body fat distribution, but rate of responder was
      significantly higher in MR group. Systolic BP decreased to a similar extent in
      both groups. Cardiometabolic risk profile improved only partly in both groups.

PMID- 21939524
TI  - Effect of ultrasound on herpes simplex virus infection in cell culture.
AB  - BACKGROUND: Ultrasound has been shown to increase the efficiency of gene
      expression from retroviruses, adenoviruses and adeno-associated viruses. The
      effect of ultrasound to stimulate cell membrane permeabilization on infection
      with an oncolytic herpes simplex virus type 1 (HSV-1) was examined. RESULTS: Vero
      monkey kidney cells were infected with HSV-1 and exposed to 1 MHz ultrasound
      after an adsorption period. The number of plaques was significantly greater than
      that of the untreated control. A combination of ultrasound and microbubbles
      further increased the plaque number. Similar results were obtained using a
      different type of HSV-1 and oral squamous cell carcinoma (SCC) cells. The
      appropriate intensity, duty cycle and time of ultrasound to increase the plaque
      number were 0.5 W/cm2, 20% duty cycle and 10 sec, respectively. Ultrasound with
      microbubbles at an intensity of 2.0 W/cm2, at 50% duty cycle, or for 40 sec
      reduced cell viability. CONCLUSION: These results indicate that ultrasound
      promotes the entry of oncolytic HSV-1 into cells. It may be useful to enhance the
      efficiency of HSV-1 infection in oncolytic virotherapy.

PMID- 21939525
TI  - Chicken interferon alpha pretreatment reduces virus replication of pandemic H1N1
      and H5N9 avian influenza viruses in lung cell cultures from different avian
      species.
AB  - BACKGROUND: Type I interferons, including interferon alpha (IFN-alpha), represent
      one of the first lines of innate immune defense against influenza virus
      infection. Following natural infection of chickens with avian influenza virus
      (AIV), transcription of IFN-alpha is quickly up regulated along with multiple
      other immune-related genes. Chicken IFN-alpha up regulates a number of important
      anti-viral response genes and has been demonstrated to be an important cytokine
      to establish anti-viral immunity. However, the mechanisms by which interferon
      inhibit virus replication in avian species remains unknown as does the biological
      activity of chicken interferon in other avian species. METHODS: In these studies,
      we assessed the protective potential of exogenous chicken IFN-alpha applied to
      chicken, duck, and turkey primary lung cell cultures prior to infection with the
      pandemic H1N1 virus (A/turkey/Virginia/SEP-4/2009) and an established avian H5N9
      virus (A/turkey/Wisconsin/1968). Growth kinetics and induction of select immune
      response genes, including IFN-alpha and myxovirus-resistance gene I (Mx), as well
      as proinflammatory cytokines (IL-1beta and IL-6), were measured in response to
      chicken IFN-alpha and viral infection over time. RESULTS: Results demonstrate
      that pretreatment with chicken IFN-alpha before AIV infection significantly
      reduced virus replication in both chicken-and turkey-origin lung cells and to a
      lesser degree the duck-origin cells. Virus growth was reduced by approximately
      200-fold in chicken and turkey cells and 30-fold in duck cells after 48 hours of
      incubation. Interferon treatment also significantly decreased the interferon and
      proinflammatory response during viral infection. In general, infection with the
      H1N1 virus resulted in an attenuated interferon and proinflammatory response in
      these cell lines, compared to the H5N9 virus. CONCLUSIONS: Taken together, these
      studies show that chicken IFN-alpha reduces virus replication, lower host innate
      immune response following infection, and is biologically active in other avian
      species.

PMID- 21939526
TI  - Developing quality indicators for the care of HIV-infected pregnant women in the
      Dutch Caribbean.
AB  - BACKGROUND: Effective interventions to prevent mother-to-child HIV transmission
      (PMTCT) exist and when properly applied reduce the risk of vertical HIV
      transmission. As part of optimizing PMTCT in the Dutch Caribbean we developed a
      set of valid and applicable indicators in order to assess the quality of care in
      HIV-infected (pregnant) women and their newborns. METHODS: A multidisciplinary
      expert panel of 19 experts reviewed and prioritized recommendations extracted
      from locally used international PMTCT guidelines according to a 3-step-modified
      Delphi procedure. Subsequently, the feasibility, sample size, inter-observer
      reliability, sensitivity to change and case mixed stability of the potential
      indicators were tested for a data set of 153 HIV-infected women, 108 pregnancies
      of HIV-infected women and 79 newborns of HIV-infected women in Aruba, Curacao and
      St Maarten from 2000 to 2010. RESULTS: The panel selected and prioritized 13
      potential indicators. Applicability could not be tested for 4 indicators
      regarding HIV-screening in pregnant women because of lack of data. Four
      indicators performed satisfactorily for Curacao ('monitoring CD4-cell count',
      'monitoring HIV-RNA levels', 'intrapartum antiretroviral therapy and infant
      prophylaxis if antepartum antiretroviral therapy was not received', 'scheduled
      caesarean delivery') and 3 for St Maarten ('monitoring CD4-cell count',
      'monitoring HIV-RNA levels', 'discuss and provide combined antiretroviral therapy
      to all HIV-infected pregnant women') whilst none for Aruba. CONCLUSIONS: A
      systemic evidence-and consensus-based approach was used to develop quality
      indicators in 3 Dutch Caribbean settings. The varying results of the
      applicability testing accentuate the necessity of applicability testing even in,
      at first, comparable settings.

PMID- 21939527
TI  - A new gene expression signature, the ClinicoMolecular Triad Classification, may
      improve prediction and prognostication of breast cancer at the time of diagnosis.
AB  - INTRODUCTION: When making treatment decisions, oncologists often stratify breast
      cancer (BC) into a low-risk group (low-grade estrogen receptor-positive (ER+)),
      an intermediate-risk group (high-grade ER+) and a high-risk group that includes
      Her2+ and triple-negative (TN) tumors (ER-/PR-/Her2-). None of the currently
      available gene signatures correlates to this clinical classification. In this
      study, we aimed to develop a test that is practical for oncologists and offers
      both molecular characterization of BC and improved prediction of prognosis and
      treatment response. METHODS: We investigated the molecular basis of such clinical
      practice by grouping Her2+ and TN BC together during clustering analyses of the
      genome-wide gene expression profiles of our training cohort, mostly derived from
      fine-needle aspiration biopsies (FNABs) of 149 consecutive evaluable BC. The
      analyses consistently divided these tumors into a three-cluster pattern,
      similarly to clinical risk stratification groups, that was reproducible in
      published microarray databases (n = 2,487) annotated with clinical outcomes. The
      clinicopathological parameters of each of these three molecular groups were also
      similar to clinical classification. RESULTS: The low-risk group had good outcomes
      and benefited from endocrine therapy. Both the intermediate- and high-risk groups
      had poor outcomes, and their BC was resistant to endocrine therapy. The latter
      group demonstrated the highest rate of complete pathological response to
      neoadjuvant chemotherapy; the highest activities in Myc, E2F1, Ras, beta-catenin
      and IFN-gamma pathways; and poor prognosis predicted by 14 independent prognostic
      signatures. On the basis of multivariate analysis, we found that this new gene
      signature, termed the "ClinicoMolecular Triad Classification" (CMTC), predicted
      recurrence and treatment response better than all pathological parameters and
      other prognostic signatures. CONCLUSIONS: CMTC correlates well with current
      clinical classifications of BC and has the potential to be easily integrated into
      routine clinical practice. Using FNABs, CMTC can be determined at the time of
      diagnostic needle biopsies for tumors of all sizes. On the basis of using public
      databases as the validation cohort in our analyses, CMTC appeared to enable
      accurate treatment guidance, could be made available in preoperative settings and
      was applicable to all BC types independently of tumor size and receptor and nodal
      status. The unique oncogenic signaling pathway pattern of each CMTC group may
      provide guidance in the development of new treatment strategies. Further
      validation of CMTC requires prospective, randomized, controlled trials.

PMID- 21939528
TI  - erbB3 recruitment of insulin receptor substrate 1 modulates insulin-like growth
      factor receptor signalling in oestrogen receptor-positive breast cancer cell
      lines.
AB  - INTRODUCTION: Recently we reported that insulin receptor substrate 1 (IRS-1),
      classically an adaptor protein for the insulin-like growth factor type I receptor
      (IGF-IR), associates with the epidermal growth factor receptor in oestrogen
      receptor (ER)-positive (ER+) tamoxifen-resistant breast cancer cells. In this
      study, we examined whether IRS-1 also associates with another erbB receptor
      family member, erbB3, and what impact this might have on IGF-IR signalling in
      three ER+ breast cancer cell lines. METHODS: Immunoprecipitation and Western blot
      analysis were utilised to examine the potential association between erbB3 and IRS
      1 in MCF-7, T47D and BT-474 cells in the absence and presence of the erbB3/4
      ligand heregulin beta1 (HRGbeta1). Subsequently, the impact of a selective IGF
      IR/IR inhibitor 4-anilino-5-bromo-2-[4-(2-hydroxy-3-(N, N
      dimethylamino)propoxy)anilino]pyrimidine on this association and HRGbeta1
      signalling was assessed in these cell lines. Immunohistochemical analysis of a
      small cohort of ER+ breast cancer patient samples was also performed to determine
      the potential clinical relevance of this novel interaction. RESULTS:
      Immunoprecipitation and Western blot analysis revealed an interaction between
      erbB3 and IRS-1 in MCF-7, T47D and BT-474 cells, with HRGbeta1 significantly
      enhancing this recruitment and promoting IRS-1 phosphorylation at Y612. IRS-1
      participates in erbB3 signalling in MCF-7 and T47D cells as IRS-1 knockdown
      impaired HRGbeta1 signalling. Importantly, recruitment of IRS-1 by erbB3 reduced
      IRS-1 association with IGF-IR in MCF-7 and T47D cells, whilst blockade of IGF-IR
      enhanced erbB3-IRS-1 interaction and sensitised both cell lines to HRGbeta1,
      allowing HRGbeta1 to override IGF-IR blockade. Consequently, suppression of IRS-1
      signalling enhanced the effects of IGF-IR inhibition in these cells. This novel
      interaction may have clinical relevance, as immunohistochemical analysis of a
      small ER+ breast tumour series revealed significant positive correlations between
      phosphorylated IRS-1 Y612 expression and total erbB3, phosphorylated Akt and Ki
      67 expression. CONCLUSIONS: IRS-1 can be recruited to IGF-IR and erbB3 in ER+
      breast cancer cells, and this provides an adaptive resistance mechanism when
      these receptors are targeted individually. Consequently, cotargeting IGF-IR and
      either erbB3 or IRS-1 should prove to be a more effective strategy for the
      treatment of ER+ breast cancer.

PMID- 21939529
TI  - The association of near-infrared spectroscopy-derived tissue oxygenation
      measurements with sepsis syndromes, organ dysfunction and mortality in emergency
      department patients with sepsis.
AB  - INTRODUCTION: Near-infrared spectroscopy (NIRS) noninvasively measures peripheral
      tissue oxygen saturation (StO2). NIRS may be utilized along with a vascular
      occlusion test, in which limb blood flow is temporarily occluded and released, to
      quantify a tissue bed's rate of oxygen exchange during ischemia and recovery. The
      objective of this study was to test the hypothesis that NIRS-derived StO2
      measures (StO2 initial, StO2 occlusion and StO2 recovery) identify patients who
      are in shock and at increased risk of organ dysfunction (Sequential Organ Failure
      Assessment (SOFA) score >= 2 at 24 hours) and dying in the hospital. METHODS:
      This prospective, observational study comprised a convenience sample of three
      cohorts of adult patients (age > 17 years) at three urban university emergency
      departments: (1) a septic shock cohort (systolic blood pressure < 90 after fluid
      challenge; the "SHOCK" cohort, n = 58), (2) a sepsis without shock cohort (the
      "SEPSIS" cohort, n = 60) and emergency department patients without infection (n =
      50). We measured the StO2 initial, StO2 occlusion and StO2 recovery slopes for
      all patients. Outcomes were sepsis syndrome severity, organ dysfunction (SOFA
      score at 24 hours) and in-hospital mortality. RESULTS: Among the 168 patients
      enrolled, mean initial StO2 was lower in the SHOCK cohort than in the SEPSIS
      cohort (76% vs 81%), with an impaired occlusion slope (-10.2 and 5.2%/minute vs 
      13.1 and 4.4%/minute) and an impaired recovery slope (2.4 and 1.6%/second vs 3.9
      and 1.7%/second) (P < 0.001 for all). The recovery slope was well-correlated with
      SOFA score at 24 hours (-0.35; P < 0.001), with a promising area under the curve
      (AUC) for mortality of 0.81. The occlusion slope correlation with SOFA score at
      24 hours was 0.21 (P < 0.02), with a fair mortality AUC of 0.70. The initial StO2
      was significantly but less strongly correlated with SOFA score at 24 hours (
      0.18; P < 0.04), with a poor mortality AUC of 0.56. CONCLUSIONS: NIRS
      measurements for the StO2 initial, StO2 occlusion and StO2 recovery slope were
      abnormal in patients with septic shock compared to sepsis patients. The recovery
      slope was most strongly associated with organ dysfunction and mortality. Further
      validation is warranted. TRIAL REGISTRATION: NCT01062685.

PMID- 21939530
TI  - Serial increase of IL-12 response and human leukocyte antigen-DR expression in
      severe sepsis survivors.
AB  - INTRODUCTION: Sepsis-induced immunosuppression may result in death. The
      mechanisms of immune suppression include loss of macrophage and monocyte
      expression of the major histocompatibility complex, increased anti-inflammatory
      cytokine expression and decreased expression of proinflammatory cytokines. In
      this study, we sought to determine the mechanisms of immune suppression in severe
      sepsis by repeated detection. METHODS: We designed this prospective observational
      study to measure monocyte human leukocyte antigen (HLA)-DR expression, plasma
      cytokine levels and cytokine responses on days 1 and 7 in stimulated peripheral
      blood mononuclear cells (PBMCs) of healthy controls and patients with severe
      sepsis. RESULTS: Of the 35 enrolled patients, 23 survived for 28 days and 12
      died, 6 of whom died within 7 days. Plasma levels of IL-1beta, IL-6, IL-10, IL
      17, transforming growth factor (TGF)-beta1 and TNF-alpha were higher, but plasma
      IL-12 level was lower in septic patients than those in controls. Day 1 plasma
      levels of IL-1beta, IL-6, IL-10 and TGF-beta1 in nonsurvivors were higher than
      those in survivors. Day 7 plasma IL-10 levels in nonsurvivors were higher than in
      survivors. IL-1beta response was higher, but IL-12 and TNF-alpha responses were
      lower in septic patients than in controls. Day 1 IL-6 response was lower, but day
      1 TGF-beta1 response was higher in nonsurvivors than in survivors. Plasma IL-6
      and IL-10 levels were decreased in survivors after 6 days. IL-6 response was
      decreased in survivors after 6 days, but IL-12 response was increased. Monocyte
      percentage was higher, but positive HLA-DR percentage in monocytes and mean
      fluorescence intensity (MFI) of HLA-DR were lower in septic patients than in
      controls. MFI of HLA-DR was increased in survivors after 6 days. CONCLUSIONS:
      Monocyte HLA-DR expression and IL-12 response from PBMCs are restored in patients
      who survive severe sepsis.

PMID- 21939531
TI  - Multi-membership gene regulation in pathway based microarray analysis.
AB  - BACKGROUND: Gene expression analysis has been intensively researched for more
      than a decade. Recently, there has been elevated interest in the integration of
      microarray data analysis with other types of biological knowledge in a holistic
      analytical approach. We propose a methodology that can be facilitated for pathway
      based microarray data analysis, based on the observation that a substantial
      proportion of genes present in biochemical pathway databases are members of a
      number of distinct pathways. Our methodology aims towards establishing the state
      of individual pathways, by identifying those truly affected by the experimental
      conditions based on the behaviour of such genes. For that purpose it considers
      all the pathways in which a gene participates and the general census of gene
      expression per pathway. RESULTS: We utilise hill climbing, simulated annealing
      and a genetic algorithm to analyse the consistency of the produced results,
      through the application of fuzzy adjusted rand indexes and hamming distance. All
      algorithms produce highly consistent genes to pathways allocations, revealing the
      contribution of genes to pathway functionality, in agreement with current pathway
      state visualisation techniques, with the simulated annealing search proving
      slightly superior in terms of efficiency. CONCLUSIONS: We show that the
      expression values of genes, which are members of a number of biochemical pathways
      or modules, are the net effect of the contribution of each gene to these
      biochemical processes. We show that by manipulating the pathway and module
      contribution of such genes to follow underlying trends we can interpret
      microarray results centred on the behaviour of these genes.

PMID- 21939532
TI  - Amyloid beta protein-induced zinc sequestration leads to synaptic loss via
      dysregulation of the ProSAP2/Shank3 scaffold.
AB  - BACKGROUND: Memory deficits in Alzheimer's disease (AD) manifest together with
      the loss of synapses caused by the disruption of the postsynaptic density (PSD),
      a network of scaffold proteins located in dendritic spines. However, the
      underlying molecular mechanisms remain elusive. Since it was shown that
      ProSAP2/Shank3 scaffold assembly within the PSD is Zn2+-dependent and that the
      amyloid beta protein (Abeta) is able to bind Zn2+, we hypothesize that
      sequestration of Zn2+ ions by Abeta contributes to ProSAP/Shank platform
      malformation. RESULTS: To test this hypothesis, we designed multiple in vitro and
      in vivo assays demonstrating ProSAP/Shank dysregulation in rat hippocampal
      cultures following Abeta oligomer accumulation. These changes were independent
      from alterations on ProSAP/Shank transcriptional level. However, application of
      soluble Abeta prevented association of Zn2+ ions with ProSAP2/Shank3 in a cell
      based assay and decreased the concentration of Zn2+ clusters within dendrites.
      Zn2+ supplementation or saturation of Abeta with Zn2+ ions prior to cell
      treatment was able to counter the effects induced by Abeta on synapse density and
      ProSAP2/Shank3 levels at the PSD. Interestingly, intracellular Zn2+ levels in APP
      PS1 mice and human AD hippocampus are reduced along with a reduction in synapse
      density and synaptic ProSAP2/Shank3 and Shank1 protein levels. CONCLUSIONS: We
      conclude that sequestration of Zn2+ ions by Abeta significantly contributes to
      changes in ProSAP2/Shank3 platforms. These changes in turn lead to less
      consolidated (mature) synapses reflected by a decrease in Shank1 protein levels
      at the PSD and decreased synapse density in hippocampal neurons.

PMID- 21939533
TI  - The preference for water nipples vs. water bowls in dairy goats.
AB  - BACKGROUND: Previous studies have reported that the design of the water
      dispensers can influence the water intake in farm animals. Horses and dairy cows
      seem to prefer to drink from an open surface whereas sheep and pigs apparently
      prefer water nipples, probably because of the worse water quality in water bowls.
      The aim of the present study was to examine the preference of dairy goats for
      water nipples or water bowls. METHODS: In each of the two experiments (exp. 1,
      dry goats, exp. 2 lactating goats), 42 dairy goats were allotted into 6 groups of
      7 goats. In period 1, the goats had access to a water nipple. In period 2, they
      had access to a water bowl and in period 3 (preference test) they had access to
      both a water nipple and a water bowl. Water usage and wastage was recorded and
      water intake (water usage - water wastage) was calculated for each group for the
      two last days of each period. In experiment 2, water samples from each dispenser
      were analyzed for heterotrophy germs at 22 degrees C, Escherichia coli and
      turbidity. RESULTS: Water usage was higher from water nipples than from water
      bowls both in experiment 1 (dry goats) and experiment 2 (lactating goats). There
      was however, no difference in water intake from water nipples and water bowls. In
      the preference test (period 3), the water intake tended to be higher from the
      water nipple than from the water bowl both for the dry goats (exp. 1) and
      lactating goats (exp. 2). Especially for the dry goats, the differences between
      groups were large. Turbidity and heterotrophy germs were much higher in the
      samples from the water bowls than from the water nipples.Water wastage from the
      water bowls was negligible compared to the water nipples. From the water nipples
      the water wastage was 30% and 23% of water usage for the dry and lactating goats
      respectively. CONCLUSIONS: We conclude that type of water dispenser (nipple or
      bowl) was probably of minor importance for water intake in goats, but water bowls
      had a lower water quality.

PMID- 21939535
TI  - Bacillus Calmette-Guerin-related cold thigh abscess as an unusual cause of thigh
      swelling in infants following BCG vaccine administration: a case series.
AB  - INTRODUCTION: Thigh swelling in an infant can be a symptom of a simple benign
      condition or a life-threatening condition. We observed a cluster of thigh
      swelling episodes in infants in which the cause was Bacillus Calmette-Guerin
      related cold thigh abscess. We report this unusual case series to raise awareness
      about this diagnosis. CASE PRESENTATIONS: We performed a retrospective review of
      five infants (four boys and one girl) who presented with Bacillus Calmette-Guerin
      related left thigh abscess. The swelling was noticed by the parents at a mean
      period of three months prior to presentation. The ages at presentation were five,
      five, eight and nine months for the boys, and six months for the girl. All of the
      patients were healthy Saudi infants, and received the Bacillus Calmette-Guerin
      vaccine at birth. Clinically, all of the patients were well and did not
      demonstrate signs of systemic infection. All patients underwent needle
      aspiration, with subsequent incision and drainage in four of the five cases. The
      cultures obtained from the abscess fluids were the key to establishing the
      diagnosis. Only three patients (60%) received antituberculosis drugs. Wound
      healing lasted for a mean period of approximately seven months. Two-year follow
      up was unremarkable for all of our patients. CONCLUSIONS: Technical errors
      continue to be significant in the development of vaccine-related complications.
      Bacillus Calmette-Guerin-related cold thigh abscess is an extremely rare entity.

PMID- 21939534
TI  - Proximal screws placement in intertrochanteric fractures treated with external
      fixation: comparison of two different techniques.
AB  - BACKGROUND: To compare two different techniques of proximal pin placement for the
      treatment of intertrochanteric fractures in elderly patients utilizing the
      Orthofix Pertrochanteric Fixator. METHODS: Seventy elderly high-risk patients
      with an average age of 81 years were treated surgically for intertrochanteric
      fracture, resulting from a low energy trauma. Patients were randomly divided in
      two groups regarding to the proximal pin placement technique. In Group A the
      proximal pins were inserted in a convergent way, while in Group B were inserted
      in parallel. RESULTS: All fractures healed uneventfully after a mean time of 98
      days. The fixator was well accepted and no patient had significant difficulties
      while sitting or lying. The mean VAS score was 5.4 in group A and 5.7 in group B.
      At 12 months after surgery, in group A the average Harris Hip Score and the
      Palmer and Parker mobility score was 67 and 5.8, respectively. In group B, the
      average Harris Hip Score and the Palmer and Parker mobility score was 62 and 5.6,
      respectively. No statistically significant difference was found regarding the
      functional outcome. The mean radiographic exposure during pin insertion in Group
      A and Group B was 15 and 6 seconds, respectively. The difference between the two
      groups, regarding the radiographic exposure, was found to be significant.
      CONCLUSION: Proximal screw placement in a parallel way is simple, with
      significant less radiation exposure and shorter intraoperative duration. In
      addition, fixation stability is equal compared to convergent pin placement.

PMID- 21939536
TI  - Mycobacterium chimaera pulmonary infection complicating cystic fibrosis: a case
      report.
AB  - BACKGROUND: Mycobacterium chimaera is a recently described species within the
      Mycobacterium avium complex. Its pathogenicity in respiratory tract infection
      remains disputed. It has never been isolated during cystic fibrosis respiratory
      tract infection. CASE PRESENTATION: An 11-year-old boy of Asian ethnicity who was
      born on Reunion Island presented to our hospital with cystic fibrosis after a
      decline in his respiratory function over the course of seven years. We found that
      the decline in his respiratory function was correlated with the persistent
      presence of a Mycobacterium avium complex organism further identified as M.
      chimaera. CONCLUSION: Using sequencing-based methods of identification, we
      observed that M. chimaera organisms contributed equally to respiratory tract
      infections in patients with cystic fibrosis when compared with M. avium subsp.
      hominissuis isolates. We believe that M. chimaera should be regarded as an
      emerging opportunistic respiratory pathogen in patients with cystic fibrosis,
      including young children, and that its detection warrants long-lasting
      appropriate anti-mycobacterial treatment to eradicate it.

PMID- 21939537
TI  - Patients presenting with miliaria while wearing flame resistant clothing in high
      ambient temperatures: a case series.
AB  - INTRODUCTION: Clothing can be a cause of occupational dermatitis. Frequent causes
      of clothing-related dermatological problems can be the fabric itself and/or
      chemical additives used in the laundering process, friction from certain fabrics
      excessively rubbing the skin, or heat retention from perspiration-soaked clothing
      in hot working environments. To the best of our knowledge, these are the first
      reported cases of miliaria rubra associated with prolonged use of flame resistant
      clothing in the medical literature. CASE PRESENTATION: We report 18 cases (14 men
      and 4 women, with an age range of 19 to 37 years) of moderate to severe skin
      irritation associated with wearing flame resistant clothing in hot arid
      environments (temperature range: 39 to 50 degrees C, 5% to 25% relative
      humidity). We describe the medical history in detail of a 23-year-old Caucasian
      woman and a 31-year-old African-American man. A summary of the other 16 patients
      is also provided. CONCLUSIONS: These cases illustrate the potential serious
      nature of miliaria with superimposed Staphylococcus infections. All 18 patients
      fully recovered with topical skin treatment and modifications to their dress
      ensemble. Clothing, in particular blend fabrics, must be thoroughly laundered to
      adequately remove detergent residue. While in hot environments, individuals with
      sensitive skin should take the necessary precautions such as regular changing of
      clothing and good personal hygiene to ensure that their skin remains as dry and
      clean as possible. It is also important that they report to their health care
      provider as soon as skin irritation or rash appears to initiate any necessary
      medical procedures. Miliaria rubra can take a week or longer to clear, so removal
      of exposure to certain fabric types may be necessary.

PMID- 21939538
TI  - Hybridization and massive mtDNA unidirectional introgression between the closely
      related Neotropical toads Rhinella marina and R. schneideri inferred from mtDNA
      and nuclear markers.
AB  - BACKGROUND: The classical perspective that interspecific hybridization in animals
      is rare has been changing due to a growing list of empirical examples showing the
      occurrence of gene flow between closely related species. Using sequence data from
      cyt b mitochondrial gene and three intron nuclear genes (RPL9, c-myc, and RPL3)
      we investigated patterns of nucleotide polymorphism and divergence between two
      closely related toad species R. marina and R. schneideri. By comparing levels of
      differentiation at nuclear and mtDNA levels we were able to describe patterns of
      introgression and infer the history of hybridization between these species.
      RESULTS: All nuclear loci are essentially concordant in revealing two well
      differentiated groups of haplotypes, corresponding to the morphologically-defined
      species R. marina and R. schneideri. Mitochondrial DNA analysis also revealed two
      well-differentiated groups of haplotypes but, in stark contrast with the nuclear
      genealogies, all R. schneideri sequences are clustered with sequences of R.
      marina from the right Amazon bank (RAB), while R. marina sequences from the left
      Amazon bank (LAB) are monophyletic. An Isolation-with-Migration (IM) analysis
      using nuclear data showed that R. marina and R. schneideri diverged at ~ 1.69 Myr
      (early Pleistocene), while R. marina populations from LAB and RAB diverged at ~
      0.33 Myr (middle Pleistocene). This time of divergence is not consistent with the
      split between LAB and RAB populations obtained with mtDNA data (~ 1.59 Myr),
      which is notably similar to the estimate obtained with nuclear genes between R.
      marina and R. schneideri. Coalescent simulations of mtDNA phylogeny under the
      speciation history inferred from nuclear genes rejected the hypothesis of
      incomplete lineage sorting to explain the conflicting signal between mtDNA and
      nuclear-based phylogenies. CONCLUSIONS: The cytonuclear discordance seems to
      reflect the occurrence of interspecific hybridization between these two closely
      related toad species. Overall, our results suggest a phenomenon of extensive
      mtDNA unidirectional introgression from the previously occurring R. schneideri
      into the invading R. marina. We hypothesize that climatic-induced range shifts
      during the Pleistocene/Holocene may have played an important role in the observed
      patterns of introgression.

PMID- 21939539
TI  - Transcriptome analysis and comparison reveal divergence between two invasive
      whitefly cryptic species.
AB  - BACKGROUND: Invasive species are valuable model systems for examining the
      evolutionary processes and molecular mechanisms associated with their specific
      characteristics by comparison with closely related species. Over the past 20
      years, two species of the whitefly Bemisia tabaci species complex, Middle East
      Asia Minor 1 (MEAM1) and Mediterranean (MED), have both spread from their origin
      Middle East/Mediterranean to many countries despite their apparent differences in
      many life history parameters. Previously, we have sequenced the transcriptome of
      MED. In this study, we sequenced the transcriptome of MEAM1 and took a
      comparative genomic approach to investigate the transcriptome evolution and the
      genetic factors underlying the differences between MEAM1 and MED. RESULTS: Using
      Illumina sequencing technology, we generated 17 million sequencing reads for
      MEAM1. These reads were assembled into 57,741 unique sequences and 15,922
      sequences were annotated with an E-value above 10-5. Compared with the MED
      transcriptome, we identified 3,585 pairs of high quality orthologous genes and
      inferred their sequence divergences. The average differences in coding, 5'
      untranslated and 3' untranslated region were 0.83%, 1.66% and 1.43%,
      respectively. The level of sequence divergence provides additional support to the
      proposition that MEAM1 and MED are two species. Based on the ratio of
      nonsynonymous and synonymous substitutions, we identified 24 sequences that have
      evolved in response to positive selection. Many of those genes are predicted to
      be involved in metabolism and insecticide resistance which might contribute to
      the divergence of the two whitefly species. CONCLUSIONS: Our data present a
      comprehensive sequence comparison between the two invasive whitefly species. This
      study will provide a road map for future investigations on the molecular
      mechanisms underlying their biological differences.

PMID- 21939540
TI  - Roles of RpoN in the resistance of Campylobacter jejuni under various stress
      conditions.
AB  - BACKGROUND: Campylobacter jejuni is a leading foodborne pathogen worldwide.
      Despite the fastidious nature of C. jejuni growth, increasing numbers of human
      campylobacteriosis suggest that C. jejuni may possess unique mechanisms to
      survive under various stress conditions. C. jejuni possesses only three sigma
      factors (FliA, RpoD, and RpoN) and lacks stress-defense sigma factors. Since FliA
      and RpoD are dedicated to flagella synthesis and housekeeping, respectively, in
      this study, we investigated the role of RpoN in C. jejuni's defense against
      various stresses. RESULTS: Survivability of an rpoN mutant was compared with the
      wild-type C. jejuni under various stress conditions. While the growth of the rpoN
      mutant was as comparably as that of the wild type in shaking cultures, the rpoN
      mutant exhibited significant survival defects when cultured statically. The rpoN
      mutant was more sensitive to osmotic stress (0.8% NaCl) with abnormally-elongated
      cell morphology. Compared to the wile type, the rpoN mutant was more susceptible
      to acid stress (pH 5) and more resistant to hydrogen peroxide. However, the rpoN
      mutation had little effect on the resistance of C. jejuni to alkaline pH, heat,
      cold and antimicrobials. CONCLUSIONS: The results demonstrate that RpoN plays an
      important role in C. jejuni's defense against various stresses which this
      bacterial pathogen may encounter during transmission to and infection of humans.

PMID- 21939541
TI  - Expression of the Flp proteins by Haemophilus ducreyi is necessary for virulence
      in human volunteers.
AB  - BACKGROUND: Haemophilus ducreyi, the causative agent of the sexually transmitted
      disease chancroid, contains a flp (fimbria like protein) operon that encodes
      proteins predicted to contribute to adherence and pathogenesis. H. ducreyi
      mutants that lack expression of Flp1 and Flp2 or TadA, which has homology to
      NTPases of type IV secretion systems, have decreased abilities to attach to and
      form microcolonies on human foreskin fibroblasts (HFF). A tadA mutant is
      attenuated in its ability to cause disease in human volunteers and in the
      temperature dependent rabbit model, but a flp1flp2 mutant is virulent in rabbits.
      Whether a flp deletion mutant would cause disease in humans is not clear.
      RESULTS: We constructed 35000HPDeltaflp1-3, a deletion mutant that lacks
      expression of all three Flp proteins but has an intact tad secretion system.
      35000HPDeltaflp1-3 was impaired in its ability to form microcolonies and to
      attach to HFF in vitro when compared to its parent (35000HP). Complementation of
      the mutant with flp1-3 in trans restored the parental phenotype. To test whether
      expression of Flp1-3 was necessary for virulence in humans, ten healthy adult
      volunteers were experimentally infected with a fixed dose of 35000HP (ranging
      from 54 to 67 CFU) on one arm and three doses of 35000HPDeltaflp1-3 (ranging from
      63 to 961 CFU) on the other arm. The overall papule formation rate for the parent
      was 80% (95% confidence interval, CI, 55.2%-99.9%) and for the mutant was 70.0%
      (95% CI, 50.5%-89.5%) (P = 0.52). Mutant papules were significantly smaller
      (mean, 11.2 mm2) than were parent papules (21.8 mm2) 24 h after inoculation (P =
      0.018). The overall pustule formation rates were 46.7% (95% CI 23.7-69.7%) at 30
      parent sites and 6.7% (95% CI, 0.1-19.1%) at 30 mutant sites (P = 0.001).
      CONCLUSION: These data suggest that production and secretion of the Flp proteins
      contributes to microcolony formation and attachment to HFF cells in vitro.
      Expression of flp1-3 is also necessary for H. ducreyi to initiate disease and
      progress to pustule formation in humans. Future studies will focus on how Flp
      proteins contribute to microcolony formation and attachment in vivo.

PMID- 21939542
TI  - Perceived barriers to guideline adherence: a survey among general practitioners.
AB  - BACKGROUND: Despite considerable efforts to promote and support guideline use,
      adherence is often suboptimal. Barriers to adherence vary not only across
      guidelines but also across recommendations within guidelines. The aim of this
      study was to assess the perceived barriers to guideline adherence among GPs by
      focusing on key recommendations within guidelines. METHODS: We conducted a cross
      sectional electronic survey among 703 GPs in the Netherlands. Sixteen key
      recommendations were derived from four national guidelines. Six statements were
      included to address the attitudes towards guidelines in general. In addition, GPs
      were asked to rate their perceived adherence (one statement) and the perceived
      barriers (fourteen statements) for each of the key recommendations, based on an
      existing framework. RESULTS: 264 GPs (38%) completed the questionnaire. Although
      35% of the GPs reported difficulties in changing routines and habits to follow
      guidelines, 89% believed that following guidelines leads to improved patient
      care. Perceived adherence varied between 52 and 95% across recommendations (mean:
      77%). The most perceived barriers were related to external factors, in particular
      patient ability and behaviour (mean: 30%) and patient preferences (mean: 23%).
      Lack of applicability of recommendations in general (mean: 22%) and more
      specifically to individual patients (mean: 25%) were also frequently perceived as
      barriers. The scores on perceived barriers differed largely between
      recommendations [minimum range 14%; maximum range 67%]. CONCLUSIONS: Dutch GPs
      have a positive attitude towards the NHG guidelines, report high adherence rates
      and low levels of perceived barriers. However, the perceived adherence and
      perceived barriers varied largely across recommendations. The most perceived
      barriers across recommendations are patient related, suggesting that current
      guidelines do not always adequately incorporate patient preferences, needs and
      abilities. It may be useful to provide tools such as decision aids, supporting
      the flexible use of guidelines to individual patients in practice.

PMID- 21939543
TI  - Giant pedunculated hepatocellular carcinoma with hemangioma mimicking intestinal
      obstruction.
AB  - BACKGROUND: Pedunculated hepatocellular carcinoma (P-HCC) has rarely been
      reported and is characteristically large and encapsulated. Only sporadic cases
      have been published, in which P-HCC was combined with other liver tumors (mostly
      benign), making the diagnosis difficult. CASE PRESENTATION: We report a patient
      who was admitted to our hospital with clinical features of intestinal obstruction
      and a palpable mass in the right iliac fossa. Ultrasound, computed tomography and
      magnetic resonance imaging demonstrated an encapsulated mass of unclear origin
      and characteristics of liver hemangioma. Laboratory tests revealed elevated alpha
      fetoprotein (> 800 ng/ml) and cancer antigen 125 (> 51.2 U/ml). With a possible
      diagnosis of giant liver hemangioma, we proceeded to surgery. During surgery, a
      giant pedunculated tumor was discovered on the inferior surface of the right lobe
      of the liver, hanging free in the right abdominal cavity towards the right iliac
      fossa. The macroscopic appearance of the tumor was compatible with liver
      hemangioma. Tumor resection was performed at a safe distance, including the
      pedicle. The rest of the liver appeared normal. Histopathological examination
      revealed grade II and III HCC (according to Edmondson-Steiner's classification)
      with nodular configuration, central necrosis, and infiltration of the capsule.
      Underneath the tumor capsule, residual tissue of a cavernous hemangioma was
      recognized. The resection margins were free of neoplastic tissue. CONCLUSION:
      This rare presentation of a giant P-HCC combined with a hemangioma with features
      of intestinal obstruction confirmed the diagnostic difficulties of similar cases,
      and required prompt surgical treatment. Therefore, patients benefit from surgical
      resection because both the capsule and the pedicle prevent vascular invasion,
      therefore improving prognosis.

PMID- 21939544
TI  - Invasive fungal sinusitis in patients with hematological malignancy: 15 years
      experience in a single university hospital in Taiwan.
AB  - BACKGROUND: Risk factors and outcomes in hematological patients who acquire
      invasive fungal sinusitis (IFS) are infrequently reported in the modern medical
      era. METHOD: A retrospective study of hospitalized patients with hematological
      disease was conducted at National Taiwan University Hospital between January 1995
      and December 2009. RESULTS: Clinical characteristics and outcomes with their
      associated radiographic and microbiological findings were analyzed. Forty-six
      patients with IFS and 64 patients with chronic non-invasive sinusitis were
      enrolled as comparsion. IFS developed more commonly in patients with acute
      myeloid leukemia (AML) and with prolonged neutropenia (absolute neutrophil count
      less than 500/mm3 for more than 10 days) (p < 0.001). Aspergillus flavus was the
      most common pathogen isolated (44%). Serum Aspergillus galactomannan antigen was
      elevated in seven of eleven patients (64%) with IFS caused by aspergillosis but
      negative for all three patients with mucormycosis. Bony erosion and extra-sinus
      infiltration was found in 15 of 46 (33%) patients on imaging. Overall, 19 of 46
      patients (41.3%) died within 6 weeks. Patients with disease subtype of AML (p =
      0.044; Odds Ratio [OR], 5.84; 95% confidence interval [95% CI], 1.02-30.56) and
      refractory leukemia status (p = 0.05; OR, 4.27; 95% CI, 1.003-18.15) had worse
      prognosis. Multivariate analysis identified surgical debridement as an
      independent good prognostic factor (p = 0.047) in patients with IFS. CONCLUSIONS:
      Patients of AML with prolonged neutropenia (> 10 days) had significantly higher
      risk of IFS. Early introduction of anti-fungal agent and aggressive surgical
      debridement potentially decrease morbidity and mortality in high risk patients
      with IFS.

PMID- 21939545
TI  - Antiretroviral treatment-induced dyslipidemia in HIV-infected patients is
      influenced by the APOC3-related rs10892151 polymorphism.
AB  - BACKGROUND: The recently observed association between the APOC3-related
      rs10892151 polymorphism and serum triglyceride levels has prompted us the
      possibility to explore whether this genetic variant may play a major role in
      human immunodeficiency virus (HIV)/antiretroviral therapy-induced dyslipidemia.
      METHODS: We determined the rs10892151 genotype distribution and serum
      apolipoprotein (apo) C-III concentration in a group of HIV-infected patients (n =
      208) and in a group of age and sex-matched healthy volunteers (n = 200).
      Circulating lipid and lipoprotein levels were followed for 12 months after
      antiretroviral treatment initiation in the HIV-infected group. RESULTS: There
      were no significant variations in the frequency of the A allele between the
      healthy and HIV-infected groups (7.5 vs. 8.6%, respectively; p = 0.7);
      additionally, the A allele was not related to serum apo C-III concentration.
      However, among patients receiving protease inhibitor (PI) treatment, carriers of
      the A allele had significantly increased serum triglyceride (5.76 +/- 2.54
      mmol/L) and total cholesterol (6.63 +/- 2.85 mmol/L) concentrations together with
      depressed levels of HDL-cholesterol (0.75 +/- 0.3 mmol/L) when compared with
      patients not carrying the allele (2.43 +/- 1.32, 5.2 +/- 2.17 and 1.24 +/- 0.4
      mmol/L, respectively) at the end of the study. This effect was only evident for
      HDL-cholesterol concentration when patients were treated with non-nucleoside
      reverse transcriptase inhibitors (1.05 +/- 0.4 vs. 1.28 +/- 0.4 mmol/L).
      CONCLUSIONS: The A allelic variant of the rs10892151 polymorphism is not
      associated with serum apo C-III concentration, but predisposes HIV-infected
      patients to less favorable lipid profile, particularly in those patients treated
      with PIs.

PMID- 21939546
TI  - An entire exon 3 germ-line rearrangement in the BRCA2 gene: pathogenic relevance
      of exon 3 deletion in breast cancer predisposition.
AB  - BACKGROUND: Germ-line mutations in the BRCA1 and BRCA2 genes are major
      contributors to hereditary breast/ovarian cancer. Large rearrangements are less
      frequent in the BRCA2 gene than in BRCA1. We report, here, the first total
      deletion of exon 3 in the BRCA2 gene that was detected during screening of 2058
      index cases from breast/ovarian cancer families for BRCA2 large rearrangements.
      Deletion of exon 3, which is in phase, does not alter the reading frame. Low
      levels of alternative transcripts lacking exon 3 (Delta3 delta3 transcript) have
      been reported in normal tissues, which raises the question whether deletion of
      exon 3 is pathogenic. METHODS: Large BRCA2 rearrangements were analysed by QMPSF
      (Quantitative Multiplex PCR of Short Fluorescent Fragments) or MLPA (Multiplex
      Ligation-Dependent Probe Amplification). The exon 3 deletion was characterized
      with a "zoom-in" dedicated CGH array to the BRCA2 gene and sequencing. To
      determine the effect of exon 3 deletion and assess its pathogenic effect, three
      methods of transcript quantification were used: fragment analysis of FAM-labelled
      PCR products, specific allelic expression using an intron 2 polymorphism and
      competitive quantitative RT-PCR. RESULTS: Large rearrangements of BRCA2 were
      detected in six index cases out of 2058 tested (3% of all deleterious BRCA2
      mutations). This study reports the first large rearrangement of the BRCA2 gene
      that includes all of exon 3 and leads to an in frame deletion of exon 3 at the
      transcriptional level. Thirty five variants in exon 3 and junction regions of
      BRCA2 are also reported, that contribute to the interpretation of the
      pathogenicity of the deletion. The quantitative approaches showed that there are
      three classes of delta3 BRCA2 transcripts (low, moderate and exclusive).
      Exclusive expression of the delta3 transcript by the mutant allele and
      segregation data provide evidence for a causal effect of the exon 3 deletion.
      CONCLUSION: This paper highlights that large rearrangements and total deletion of
      exon 3 in the BRCA2 gene could contribute to hereditary breast and/or ovarian
      cancer. In addition, our findings suggest that, to interpret the pathogenic
      effect of any variants of exon 3, both accurate transcript quantification and co
      segregation analysis are required.

PMID- 21939547
TI  - Controversies in neurology: why monoamine oxidase B inhibitors could be a good
      choice for the initial treatment of Parkinson's disease.
AB  - BACKGROUND: Early initiation of pharmacotherapy in Parkinson's disease (PD) is
      nowadays widely advocated by experts since the delay of treatment has shown to be
      associated with a significant deterioration of health related quality of life in
      affected patients. Due to marked advances in PD treatment during the last
      decades, physicians are nowadays fortunately equipped with a variety of
      substances that can effectively ameliorate emerging motor symptoms of the
      disease, among them levodopa, dopamine agonists and monoamine oxidase type B (MAO
      B) inhibitors. Despite numerous drug intervention trials in early PD, there is
      however still ongoing controversy among neurologists which substance to use for
      the initial treatment of the disease. DISCUSSION: In multiple studies, MAO-B
      inhibitors, such as selegiline and rasagiline, have shown to provide mild
      symptomatic effects, delay the need for levodopa, and to reduce the incidence of
      motor fluctuations. Although their symptomatic efficacy is inferior compared to
      dopamine agonists and levodopa, MAO-B inhibitors undoubtedly have fewer side
      effects and are easy to administer. In contrary to their competitors, MAO-B
      inhibitors may furthermore offer a chance for disease modification, which so far
      remains a major unmet need in the management of PD and eventually makes them
      ideal candidates for the early treatment of the disease. SUMMARY: MAO-B
      inhibitors may constitute a preferable therapeutic option for early PD, mainly
      due to their favourable safety profile and their putative neuroprotective
      capabilities. Since the symptomatic effects of MAO-B inhibitors are comparatively
      mild, dopamine agonists and levodopa should however be considered for initial
      treatment in those PD patients, in whom robust and immediate symptomatic relief
      needs to be prioritized.

PMID- 21939548
TI  - Initial clinical experience with a novel vertebral augmentation system for
      treatment of symptomatic vertebral compression fractures: a case series of 26
      consecutive patients.
AB  - BACKGROUND: Minimally invasive vertebral augmentation procedures are widely used
      to treat vertebral compression fractures although procedural
      polymethylmethacrylate cement leakage remains common. We report herein our
      initial experience with a novel vertebral augmentation technique designed to
      treat symptomatic vertebral osteoporotic fractures and osteolytic metastases with
      minimal cement extravasation. METHODS: Forty-two vertebral fractures were
      identified in 26 consecutive patients (mean age 74 +/- 9 years). All patients
      were treated with a novel percutaneous vertebral augmentation device (Kiva VCF
      Treatment System, Benvenue Medical, Santa Clara, CA, USA). Indications for
      surgery included recent (<= 3 months) symptomatic osteoporotic vertebral fracture
      (n = 34) and pathologic vertebral fractures (e.g. metabolic bone disease,
      myeloma, metastasis) (n = 8) located between T10 and S1. Patient outcomes were
      evaluated pre-treatment and at 2- and 6-month follow-up visits. Postoperative
      cement extravasation was assessed with computed tomography. Patient-reported back
      pain was quantified using an 11-point numeric scale. Back-specific functional
      disability was self-reported with the Oswestry Disability Index on a 0 to 100%
      scale. RESULTS: No cases of intraoperative hypotension, respiratory disturbance,
      neurological deterioration, infection, or death were observed. There were 2
      (4.8%) levels where anterior cement leakage was visible radiographically in
      patients with osteolyses. No intracanal leakage was observed. Back pain scores
      improved 71% (p < 0.001) from pre-treatment to the 6-month follow-up. Back
      function improved 56% from baseline to 6 months (p < 0.001). CONCLUSIONS: The
      initial clinical experience with the Kiva System demonstrated significant
      improvements in back pain and function with minimal and clinically insignificant
      procedural cement leakage.

PMID- 21939549
TI  - Preliminary examination of the efficacy and safety of a standardized chamomile
      extract for chronic primary insomnia: a randomized placebo-controlled pilot
      study.
AB  - BACKGROUND: Despite being the most commonly used herbal for sleep disorders,
      chamomile's (Matricaria recutita) efficacy and safety for treating chronic
      primary insomnia is unknown. We examined the preliminary efficacy and safety of
      chamomile for improving subjective sleep and daytime symptoms in patients with
      chronic insomnia. METHODS: We performed a randomized, double-blind, placebo
      controlled pilot trial in 34 patients aged 18-65 years with DSM-IV primary
      insomnia for >= 6-months. Patients were randomized to 270 mg of chamomile twice
      daily or placebo for 28-days. The primary outcomes were sleep diary measures.
      Secondary outcomes included daytime symptoms, safety assessments, and effect size
      of these measures. RESULTS: There were no significant differences between groups
      in changes in sleep diary measures, including total sleep time (TST), sleep
      efficiency, sleep latency, wake after sleep onset (WASO), sleep quality, and
      number of awakenings. Chamomile did show modest advantage on daytime functioning,
      although these did not reach statistical significance. Effect sizes were
      generally small to moderate (Cohen's d <= 0.20 to < 0.60) with sleep latency,
      night time awakenings, and Fatigue Severity Scale (FSS), having moderate effect
      sizes in favor of chamomile. However, TST demonstrated a moderate effect size in
      favor of placebo. There were no differences in adverse events reported by the
      chamomile group compared to placebo. CONCLUSION: Chamomile could provide modest
      benefits of daytime functioning and mixed benefits on sleep diary measures
      relative to placebo in adults with chronic primary insomnia. However, further
      studies in select insomnia patients would be needed to investigate these
      conclusions.

PMID- 21939550
TI  - Treatment incidence of and medical utilization for hospitalized subjects with
      pathologic fractures in Taiwan-Survey of the 2008 National Health Insurance data.
AB  - BACKGROUND: Almost all studies of pathologic fractures have been conducted based
      on patients with tumours and hospital-based data; however, in the present study,
      a nationwide epidemiological survey of pathologic fractures in Taiwan was
      performed and the medical utilization was calculated. METHODS: All claimants of
      Taiwan's National Health Insurance (NHI) Program in 2008 were included in the
      target population of this descriptive cross-sectional study. The registration and
      inpatient expenditure claims data by admission of all hospitalized subjects of
      the target population were examined and the concomitant International
      Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)
      diagnosis codes were evaluated and classified into seven major categories of
      fracture. RESULTS: A total of 5,244 incident cases of pathologic fracture were
      identified from the 2008 hospitalized patient claims data. The incidence of
      pathologic fracture of the humerus, distal radius/ulna, vertebrae, femoral neck,
      other part of the femur, and tibia/fibula was 0.67, 0.08, 10.58, 1.11, 0.56, and
      0.11 per 100,000 people, respectively, and patients with those fractures were
      hospitalized for 43.9 +/- 42.9, 31.1 +/- 32.9, 29. 4 +/- 34.4, 43.3 +/- 41.2,
      42.4 +/- 38.1, and 42.0 +/- 32.8 days, respectively, incurring an average medical
      cost of US$11,049 +/- 12,730, US$9,181 +/- 12,115, US$6,250 +/- 8,021, US$9,619
      +/- 8,906, US$10,646 +/- 11,024, and US$9,403 +/- 9,882, respectively. The
      percentage of patients undergoing bone surgery for pathologic fracture of the
      humerus, radius/ulna, vertebrae, femoral neck, other part of the femur, and
      tibia/fibula was 31.2%, 44.4%, 11.3%, 46.5%, 48.4%, and 52.5% respectively.
      CONCLUSIONS: Comparing Taiwan to other countries, this study observed for Taiwan
      higher medical utilization and less-aggressive surgical intervention for patients
      hospitalized with pathologic fractures.

PMID- 21939551
TI  - The transition into veterinary practice: opinions of recent graduates and final
      year students.
AB  - BACKGROUND: The transition from veterinary student to member of the veterinary
      profession is known to be challenging. This study aimed to determine and compare
      the opinions of final year veterinary students and recent graduates on graduate
      attributes that ease this transition. METHODS: The study was carried out across 3
      veterinary schools in the United Kingdom. Paper based or electronic surveys were
      used. Final year students in the 3 schools were surveyed either electronically
      (school A) or on paper (schools B and C). Student cohort sizes were 112, 227 and
      102 respectively. Recent graduates were contacted either at a reunion event
      (school A) or electronically from database records (school B and school C).
      Cohort sizes of contacted graduates were 80, 175 and 91 respectively. Respondents
      were asked to rate 42 individual attributes on a 5 point Likert scale. Focus
      groups with final year students and recent graduates and telephone interviews
      with recent graduates were carried out. Data were analysed by two researchers
      through a combination of manual coding and thematic analysis. Data were grouped
      into broad themes then sorted into narrower themes. Data were then searched for
      counter examples. RESULTS: Response rates for final year students were 34%
      (school A), 36% (school B) and 40% (school C). Response rates for recent
      graduates were 56% (school A), 20% (school B) and 11% (school C). There was a
      high level of agreement between the cohorts with respect to communication skills,
      problem solving and decision making skills, recognition of own limitations and
      the ability to cope with pressure all rated unanimously important or very
      important. Business acumen, knowledge of veterinary practice management and
      research skills were the 3 attributes ranked at the bottom of the list. Nine
      attributes were identified with a significantly different (p < 0.05) ranking
      between the cohorts. Final year students ranked veterinary clinical knowledge,
      knowledge of veterinary public health and zoonotic issues, veterinary legislation
      and veterinary practice management, commitment to continuing professional
      development and ability to evaluate information higher than recent graduates.
      Recent graduates ranked the attributes of integrity, friendliness and compassion
      higher than final year students. CONCLUSIONS: Recent graduates and final year
      students rate highly the attributes which help foster the client/veterinarian
      relationship. Recent graduates reflect that a focus on knowledge based attributes
      is less important once in practice when compared to final year. The study
      confirms the importance to recent graduates and final year students of attributes
      considered as non-technical in the transition to working in the veterinary
      profession.

PMID- 21939552
TI  - HtrA chaperone activity contributes to host cell binding in Campylobacter jejuni.
AB  - BACKGROUND: Acute gastroenteritis caused by the food-borne pathogen Campylobacter
      jejuni is associated with attachment of bacteria to the intestinal epithelium and
      subsequent invasion of epithelial cells. In C. jejuni, the periplasmic protein
      HtrA is required for efficient binding to epithelial cells. HtrA has both
      protease and chaperone activity, and is important for virulence of several
      bacterial pathogens. RESULTS: The aim of this study was to determine the role of
      the dual activities of HtrA in host cell interaction of C. jejuni by comparing an
      htrA mutant lacking protease activity, but retaining chaperone activity, with a
      DeltahtrA mutant and the wild type strain. Binding of C. jejuni to both
      epithelial cells and macrophages was facilitated mainly by HtrA chaperone
      activity that may be involved in folding of outer membrane adhesins. In contrast,
      HtrA protease activity played only a minor role in interaction with host cells.
      CONCLUSION: We show that HtrA protease and chaperone activities contribute
      differently to C. jejuni's interaction with mammalian host cells, with the
      chaperone activity playing the major role in host cell binding.

PMID- 21939553
TI  - LIN28B, LIN28A, KISS1, and KISS1R in idiopathic central precocious puberty.
AB  - BACKGROUND: Pubertal timing is a strongly heritable trait, but no single puberty
      gene has been identified. Thus, the genetic background of idiopathic central
      precocious puberty (ICPP) is poorly understood. Overall, the genetic modulation
      of pubertal onset most likely arises from the additive effect of multiple genes,
      but also monogenic causes of ICPP probably exist, as cases of familial ICPP have
      been reported. Mutations in KISS1 and KISSR, coding for kisspeptin and its
      receptor, involved in GnRH secretion and puberty onset, have been suggested
      causative for monogenic ICPP. Variation in LIN28B was associated with timing of
      puberty in genome-wide association (GWA) studies. LIN28B is a human ortholog of
      the gene that controls, through microRNAs, developmental timing in C. elegans. In
      addition, Lin28a transgenic mice manifest the puberty phenotypes identified in
      the human GWAS. Thus, both LIN28B and LIN28A may have a role in pubertal
      development and are good candidate genes for monogenic ICPP. METHODS: Thirty
      girls with ICPP were included in the study. ICPP was defined by pubertal onset
      before 8 yrs of age, and a pubertal LH response to GnRH testing. The coding
      regions of LIN28B, LIN28A, KISS1, and KISS1R were sequenced. The missense change
      in LIN28B was also screened in 132 control subjects. RESULTS: No rare variants
      were detected in KISS1 or KISS1R in the 30 subjects with ICPP. In LIN28B, one
      missense change, His199Arg, was found in one subject with ICPP. However, this
      variant was also detected in one of the 132 controls. No variation in LIN28A was
      found. CONCLUSIONS: We did not find any evidence that mutations in LIN28B or
      LIN28A would underlie ICPP. In addition, we confirmed that mutations in KISS1 and
      KISS1R are not a common cause for ICPP.

PMID- 21939554
TI  - MicroRNA signature of cis-platin resistant vs. cis-platin sensitive ovarian
      cancer cell lines.
AB  - BACKGROUND: Ovarian cancer is the leading cause of death from gynecologic cancer
      in women worldwide. According to the National Cancer Institute, ovarian cancer
      has the highest mortality rate among all the reproductive cancers in women.
      Advanced stage diagnosis and chemo/radio-resistance is a major obstacle in
      treating advanced ovarian cancer. The most commonly employed chemotherapeutic
      drug for ovarian cancer treatment is cis-platin. As with most chemotherapeutic
      drugs, many patients eventually become resistant to cis-platin and therefore,
      diminishing its effect. The efficacy of current treatments may be improved by
      increasing the sensitivity of cancer cells to chemo/radiation therapies. METHODS:
      The present study is focused on identifying the differential expression of
      regulatory microRNAs (miRNAs) between cis-platin sensitive (A2780), and cis
      platin resistant (A2780/CP70) cell lines. Cell proliferation assays were
      conducted to test the sensitivity of the two cell lines to cis-platin.
      Differential expression patterns of miRNA between cis-platin sensitive and cis
      platin resistant cell lines were analyzed using novel LNA technology. RESULTS:
      Our results revealed changes in expression of 11 miRNAs out of 1,500 miRNAs
      analyzed. Out of the 11 miRNAs identified, 5 were up-regulated in the A2780/CP70
      cell line and 6 were down regulated as compared to cis-platin sensitive A2780
      cells. Our microRNA data was further validated by quantitative real-time PCR for
      these selected miRNAs. Ingenuity Pathway Analysis (IPA) and Kyoto Encyclopedia of
      Genes and Genomes (KEGG) analysis was performed for the selected miRNAs and their
      putative targets to identify the potential pathways and networks involved in cis
      platin resistance. CONCLUSIONS: Our data clearly showed the differential
      expression of 11 miRNAs in cis-platin resistant cells, which could potentially
      target many important pathways including MAPK, TGF-beta signaling, actin
      cytoskeleton, ubiquitin mediated proteasomal pathway, Wnt signaling, mTOR
      signaling, Notch signaling, apoptosis, and many other signaling pathways.
      Manipulation of one or more of these miRNAs could be an important approach for
      ovarian cancer chemotherapy.

PMID- 21939555
TI  - Different patterns of NF-kappaB and Notch1 signaling contribute to tumor-induced
      lymphangiogenesis of esophageal squamous cell carcinoma.
AB  - BACKGROUND: Lymph node involvement and tumor-induced lymphangiogenesis appear as
      the earliest features of esophageal squamous cell carcinoma (ESCC), although the
      molecular regulatory mechanisms involved have remained unclear. Our aim was to
      investigate the contribution of NF-kappaB and Notch1 signaling to lymph node
      involvement and tumor-induced lymphangiogenesis in ESCC. MATERIAL AND METHODS: NF
      kappaB and Notch1 expression in 60 tissue samples of ESCC were assessed by
      immunohistochemical staining. The correlations of NF-kappaB and Notch1 with lymph
      node involvement, lymphatic vessel density (LVD), podoplanin, and vascular
      endothelial growth factor-C (VEGF-C) were further evaluated to determine the
      association of NF-kappaB and Notch1 expression with tumor-induced
      lymphangiogenesis. RESULTS: Chi-square tests revealed that NF-kappaB and Notch1
      expression in ESCC tissues were significant associated with lymph node
      metastasis, LVD, podoplanin, and VEGF-C expression. Strong expression of NF
      kappaB, but weak expression of Notch1, was observed in tumor tissues with lymph
      nodes involvement (P < 0.05 for both). The mean histoscores of LVD, podoplanin,
      and VEGF-C staining were higher in high-NF-kappaB-expressing tissue than in low
      expressing tissue (P < 0.05 for each). In contrast, the mean histoscores of LVD
      and VEGF-C staining were lower in high-Notch1-expressing tissue than in low
      expressing tissue (P < 0.05 for both). A multiple factors analysis of LVD and
      VEGF-C further demonstrated that LVD and VEGF-C status were significantly
      correlated with NF-kappaB and Notch1 expression in tumors. NF-kappaB and Notch1
      expression were also significantly inversely correlated (P < 0.05). CONCLUSION:
      These results suggest that different patterns of NF-kappaB and Notch1 signaling
      contribute to lymph nodes metastasis and tumor-induced lymphangiogenesis of ESCC,
      and reveal that up-regulation of NF-kappaB is associated with down-regulation of
      Notch1 in tumor tissue.

PMID- 21939557
TI  - Neuromuscular training to enhance sensorimotor and functional deficits in
      subjects with chronic ankle instability: A systematic review and best evidence
      synthesis.
AB  - OBJECTIVE: To summarise the available evidence for the efficacy of neuromuscular
      training in enhancing sensorimotor and functional deficits in subjects with
      chronic ankle instability (CAI). DESIGN: Systematic review with best evidence
      synthesis. DATA SOURCES: An electronic search was conducted through December
      2009, limited to studies published in the English language, using the Pubmed,
      CINAHL, Embase, and SPORTDiscus databases. Reference screening of all included
      articles was also undertaken. METHODS: Studies were selected if the design was a
      RCT, quasi RCT, or a CCT; the patients were adolescents or adults with confirmed
      CAI; and one of the treatment options consisted of a neuromuscular training
      programme. The primary investigator independently assessed the risk of study bias
      and extracted relevant data. Due to clinical heterogeneity, data was analysed
      using a best-evidence synthesis. RESULTS: Fourteen studies were included in the
      review. Meta-analysis with statistical pooling of data was not possible, as the
      studies were considered too heterogeneous. Instead a best evidence synthesis was
      undertaken. There is limited to moderate evidence to support improvements in
      dynamic postural stability, and patient perceived functional stability through
      neuromuscular training in subjects with CAI. There is limited evidence of
      effectiveness for neuromuscular training for improving static postural stability,
      active and passive joint position sense (JPS), isometric strength, muscle onset
      latencies, shank/rearfoot coupling, and a reduction in injury recurrence rates.
      There is limited evidence of no effectiveness for improvements in muscle fatigue
      following neuromuscular intervention. CONCLUSION: There is limited to moderate
      evidence of effectiveness in favour of neuromuscular training for various
      measures of static and dynamic postural stability, active and passive JPS,
      isometric strength, muscle onset latencies, shank/rearfoot coupling and injury
      recurrence rates. Strong evidence of effectiveness was lacking for all outcome
      measures. All but one of the studies included in the review were deemed to have a
      high risk of bias, and most studies were lacking sufficient power. Therefore, in
      future we recommend conducting higher quality RCTs using appropriate outcomes to
      assess for the effectiveness of neuromuscular training in overcoming sensorimotor
      deficits in subjects with CAI.

PMID- 21939556
TI  - New advances in leukaemia immunotherapy by the use of Chimeric Artificial Antigen
      Receptors (CARs): state of the art and perspectives for the near future.
AB  - Leukaemia immunotherapy represents a fascinating and promising field of
      translational research, particularly as an integrative approach of bone marrow
      transplantation. Adoptive immunotherapy by the use of donor-derived expanded
      leukaemia-specific T cells has showed some kind of clinical response, but the
      major advance is nowadays represented by gene manipulation of donor immune cells,
      so that they acquire strict specificity towards the tumour target and potent
      lytic activity, followed by significant proliferation, increased survival and
      possibly anti-tumour memory state. This is achieved by gene insertion of Chimeric
      T-cell Antigen Receptors (CARs), which are artificial molecules containing
      antibody-derived fragments (to bind the specific target), joined with potent
      signalling T-Cell Receptor (TCR)-derived domains that activate the manipulated
      cells. This review will discuss the main application of this approach
      particularly focusing on the paediatric setting, raising advantages and
      disadvantages and discussing relevant perspectives of use in the nearest future.

PMID- 21939558
TI  - Therapeutic effects of human umbilical cord blood-derived mesenchymal stem cells
      after intrathecal administration by lumbar puncture in a rat model of cerebral
      ischemia.
AB  - INTRODUCTION: Stem cell transplantation is a promising therapeutic strategy for
      the treatment of stroke. Mesenchymal stem cells (MSCs) are a potential cell
      source for clinical application because they can be easily obtained and
      cultivated with a high proliferative capacity. The safety and efficacy of cell
      therapy depends on the mode of cell administration. To determine the therapeutic
      potential of intrathecal administration of MSCs by lumbar puncture (LP), we
      administrated human umbilical cord blood-derived MSCs (hUCB-MSCs) intrathecally
      into the lumbar spinal cord or intravenously into the tail vein in a rat model of
      stroke, and then investigated whether hUCB-MSCs could enter the brain, survive,
      and improve post-stroke neurological functional recovery. METHODS: hUCB-MSCs (1.0
      * 10(6)) were administrated three days after stroke induced by occlusion of the
      middle cerebral artery. The presence of hUCB-MSCs and their survival and
      differentiation in the brain tissue of the rats was examined by
      immunohistochemistry. Recovery of coordination of movement after administration
      of hUCB-MSCs was examined using a Rotarod test and adhesive-removal test on the
      7th, 14th, 21st, and 28th days after ischemia. The volume of ischemic lesions
      seven days after the experimental procedure was evaluated using 2-3-5
      triphenyltetrazolium (TTC) staining. RESULTS: Rats receiving hUCB-MSCs
      intrathecally by LP had a significantly higher number of migrated cells within
      the ischemic area when compared with animals receiving cells intravenously. In
      addition, many of the cells administered intrathecally survived and a subset of
      them expressed mature neural-lineage markers, including the mature neuron marker
      NeuN and glial fibrillary acidic protein, typical of astrocytes. Animals that
      received hUCB-MSCs had significantly improved motor function and reduced ischemic
      damage when compared with untreated control animals. Regardless of the
      administration route, the group treated with 1 * 10(6) hUCB-MSCs showed better
      neurological recovery, without significant differences between the two treatment
      groups. Importantly, intrathecal administration of 5 * 10(5) hUCB-MSCs
      significantly reduced ischemic damage, but not in the intravenously treated
      group. Furthermore, the cells administered intrathecally survived and migrated
      into the ischemic area more extensively, and differentiated significantly into
      neurons and astrocytes. CONCLUSIONS: Together, these results indicate that
      intrathecal administration of MSCs by LP may be useful and feasible for MSCs
      treatment of brain injuries, such as stroke, or neurodegenerative disorders.

PMID- 21939559
TI  - Short-term effect of fenofibrate on C-reactive protein: A meta-analysis of
      randomized controlled trials.
AB  - BACKGROUND: C-reactive protein (CRP) is positively associated with risk for
      cardiovascular disease and all-cause mortality. Some but not all randomized and
      non-randomized clinical trials found significant associations between fenofibrate
      therapy and CRP but the direction and magnitude of the association varied across
      studies. The duration of treatment, patient populations and sample sizes varied
      greatly, and most short-term studies (i.e., <= 12 weeks) had fewer than 50
      patients. In this study we meta-analyzed randomized clinical trials to determine
      the short-term effect of fenofibrate on CRP. METHODS: Two reviewers independently
      searched PubMed and other online databases for short-term randomized clinical
      trials that reported CRP concentrations before and after fenofibrate treatment.
      Of the 81 studies examined, 14 studies with 540 patients were found eligible.
      Data for the change in CRP and corresponding measures of dispersion were
      extracted for use in the meta-analysis. RESULTS: The weighted mean CRP
      concentrations before and after fenofibrate therapy were 2.15 mg/L and 1.53 mg/L
      (-28.8% change), respectively. Inverse-variance weighted random effects meta
      analysis revealed that short-term fenofibrate treatment significantly lowers CRP
      by 0.58 mg/L (95% CI: 0.36-0.80). There was significant heterogeneity between
      studies (Q statistic = 64.5, P< 0.0001, I2 = 79.8%). There was no evidence of
      publication bias and sensitivity analysis revealed that omitting any of the 14
      studies did not lead to a different conclusion from the overall meta-analysis
      result. CONCLUSION: Short-term treatment with fenofibrate significantly lowers
      CRP concentration. Randomized trials that will recruit patients based with high
      baseline CRP concentrations and with change in CRP as a primary outcome are
      needed.

PMID- 21939560
TI  - Real-time feature extraction of P300 component using adaptive nonlinear principal
      component analysis.
AB  - BACKGROUND: The electroencephalography (EEG) signals are known to involve the
      firings of neurons in the brain. The P300 wave is a high potential caused by an
      event-related stimulus. The detection of P300s included in the measured EEG
      signals is widely investigated. The difficulties in detecting them are that they
      are mixed with other signals generated over a large brain area and their
      amplitudes are very small due to the distance and resistivity differences in
      their transmittance. METHODS: A novel real-time feature extraction method for
      detecting P300 waves by combining an adaptive nonlinear principal component
      analysis (ANPCA) and a multilayer neural network is proposed. The measured EEG
      signals are first filtered using a sixth-order band-pass filter with cut-off
      frequencies of 1 Hz and 12 Hz. The proposed ANPCA scheme consists of four steps:
      pre-separation, whitening, separation, and estimation. In the experiment, four
      different inter-stimulus intervals (ISIs) are utilized: 325 ms, 350 ms, 375 ms,
      and 400 ms. RESULTS: The developed multi-stage principal component analysis
      method applied at the pre-separation step has reduced the external noises and
      artifacts significantly. The introduced adaptive law in the whitening step has
      made the subsequent algorithm in the separation step to converge fast. The
      separation performance index has varied from -20 dB to -33 dB due to randomness
      of source signals. The robustness of the ANPCA against background noises has been
      evaluated by comparing the separation performance indices of the ANPCA with four
      algorithms (NPCA, NSS-JD, JADE, and SOBI), in which the ANPCA algorithm
      demonstrated the shortest iteration time with performance index about 0.03. Upon
      this, it is asserted that the ANPCA algorithm successfully separates mixed source
      signals. CONCLUSIONS: The independent components produced from the observed data
      using the proposed method illustrated that the extracted signals were clearly the
      P300 components elicited by task-related stimuli. The experiment using 350 ms ISI
      showed the best performance. Since the proposed method does not use down-sampling
      and averaging, it can be used as a viable tool for real-time clinical
      applications.

PMID- 21939561
TI  - Apolipoprotein epsilon4 polymorphism does not modify the association between body
      mass index and high-density lipoprotein cholesterol: a cross-sectional cohort
      study.
AB  - BACKGROUND: We sought to examine whether epsilon4 carrier status modifies the
      relation between body mass index (BMI) and HDL. The National Heart, Lung, and
      Blood Institute Family Heart Study included 657 families with high family risk
      scores for coronary heart disease and 588 randomly selected families of probands
      in the Framingham, Atherosclerosis Risk in Communities, and Utah Family Health
      Tree studies. We selected 1402 subjects who had epsilon4 carrier status
      available. We used generalized estimating equations to examine the interaction
      between BMI and epsilon4 allele carrier status on HDL after adjusting for age,
      gender, smoking, alcohol intake, mono- and poly-unsaturated fat intake, exercise,
      comorbidities, LDL, and family cluster. RESULTS: The mean (standard deviation)
      age of included subjects was 56.4(11.0) years and 47% were male. Adjusted means
      of HDL for normal, overweight, and obese BMI categories were 51.2(+/- 0.97),
      45.0(+/- 0.75), and 41.6(+/- 0.93), respectively, among 397 epsilon4 carriers (p
      for trend < 0.0001) and 53.6(+/- 0.62), 51.3(+/- 0.49), and 45.0(+/- 0.62),
      respectively, among 1005 non-carriers of the epsilon4 allele (p-value for trend <
      0.0001). There was no evidence for an interaction between BMI and epsilon4 status
      on HDL(p-value 0.39). CONCLUSION: Our findings do not support an interaction
      between epsilon4 allele status and BMI on HDL.

PMID- 21939563
TI  - Primary care provider perceptions of intake transition records and shared care
      with outpatient cardiac rehabilitation programs.
AB  - BACKGROUND: While it is recommended that records are kept between primary care
      providers (PCPs) and specialists during patient transitions from hospital to
      community care, this communication is not currently standardized. We aimed to
      assess the transmission of cardiac rehabilitation (CR) program intake transition
      records to PCPs and to explore PCPs' needs in communication with CR programs and
      for intake transition record content. METHOD: 144 PCPs of consenting enrollees
      from 8 regional and urban Ontario CR programs participated in this cross
      sectional study. Intake transition records were tracked from the CR program to
      the PCP's office. Sixty-six PCPs participated in structured telephone interviews.
      RESULTS: Sixty-eight (47.6%) PCPs received a CR intake transition record. Fifty
      eight (87.9%) PCPs desired intake transition records, with most wanting it
      transmitted via fax (n = 52, 78.8%). On a 5-point Likert scale, PCPs strongly
      agreed that the CR transition record met their needs for providing patient care
      (4.32 +/- 0.61), with 48 (76.2%) reporting that it improved their management of
      patients' cardiac risk. PCPs rated the following elements as most important to
      include in an intake transition record: clinical status (4.67 +/- 0.64), exercise
      test results (4.61 +/- 0.52), and the proposed patient care plan (4.59 +/- 0.71).
      CONCLUSIONS: Less than half of intake transition records are reaching PCPs,
      revealing a large gap in continuity of patient care. PCP responses should be used
      to develop an evidence-based intake transition record, and procedures should be
      implemented to ensure high-quality transitional care.

PMID- 21939562
TI  - The impact of trained patient educators on musculoskeletal clinical skills
      attainment in pre-clerkship medical students.
AB  - BACKGROUND: Despite the high burden of musculoskeletal (MSK) diseases, few
      generalists are comfortable teaching MSK physical examination (PE) skills.
      Patient Partners(r) in Arthritis (PP(r)IA) is a standardized patient educator
      program that could potentially supplement current MSK PE teaching. This study
      aims to determine if differences exist in MSK PE skills between non-MSK
      specialist physician and PP(r)IA taught students. METHODS: Pre-clerkship medical
      students attended 2-hour small group MSK PE teaching by either non-MSK specialist
      physician tutors or by PP(r)IA. All students underwent an MSK OSCE and completed
      retrospective pre-post questionnaires regarding comfort with MSK PE and interest
      in MSK. RESULTS: 83 students completed the OSCE (42 PP(r)IA, 41 physician taught)
      and 82 completed the questionnaire (42 PP(r)IA, 40 physician taught). There were
      no significant differences between groups in OSCE scores. For all questionnaire
      items, post-session ratings were significantly higher than pre-session ratings
      for both groups. In exploratory analysis PP(r)IA students showed significantly
      greater improvement in 12 of 22 questions including three of five patient-centred
      learning questions. CONCLUSIONS: PP(r)IA MSK PE teaching is as good as non-MSK
      specialist physician tutor teaching when measured by a five station OSCE and
      provide an excellent complementary resource to address current deficits in MSK PE
      teaching.

PMID- 21939564
TI  - Top scoring pairs for feature selection in machine learning and applications to
      cancer outcome prediction.
AB  - BACKGROUND: The widely used k top scoring pair (k-TSP) algorithm is a simple yet
      powerful parameter-free classifier. It owes its success in many cancer microarray
      datasets to an effective feature selection algorithm that is based on relative
      expression ordering of gene pairs. However, its general robustness does not
      extend to some difficult datasets, such as those involving cancer outcome
      prediction, which may be due to the relatively simple voting scheme used by the
      classifier. We believe that the performance can be enhanced by separating its
      effective feature selection component and combining it with a powerful classifier
      such as the support vector machine (SVM). More generally the top scoring pairs
      generated by the k-TSP ranking algorithm can be used as a dimensionally reduced
      subspace for other machine learning classifiers. RESULTS: We developed an
      approach integrating the k-TSP ranking algorithm (TSP) with other machine
      learning methods, allowing combination of the computationally efficient,
      multivariate feature ranking of k-TSP with multivariate classifiers such as SVM.
      We evaluated this hybrid scheme (k-TSP+SVM) in a range of simulated datasets with
      known data structures. As compared with other feature selection methods, such as
      a univariate method similar to Fisher's discriminant criterion (Fisher), or a
      recursive feature elimination embedded in SVM (RFE), TSP is increasingly more
      effective than the other two methods as the informative genes become
      progressively more correlated, which is demonstrated both in terms of the
      classification performance and the ability to recover true informative genes. We
      also applied this hybrid scheme to four cancer prognosis datasets, in which k
      TSP+SVM outperforms k-TSP classifier in all datasets, and achieves either
      comparable or superior performance to that using SVM alone. In concurrence with
      what is observed in simulation, TSP appears to be a better feature selector than
      Fisher and RFE in some of the cancer datasets CONCLUSIONS: The k-TSP ranking
      algorithm can be used as a computationally efficient, multivariate filter method
      for feature selection in machine learning. SVM in combination with k-TSP ranking
      algorithm outperforms k-TSP and SVM alone in simulated datasets and in some
      cancer prognosis datasets. Simulation studies suggest that as a feature selector,
      it is better tuned to certain data characteristics, i.e. correlations among
      informative genes, which is potentially interesting as an alternative feature
      ranking method in pathway analysis.

PMID- 21939565
TI  - Relation between mean arterial pressure and renal function in the early phase of
      shock: a prospective, explorative cohort study.

PMID- 21939566
TI  - [Langerhans cell histiocytosis of the dens axis].
AB  - BACKGROUND: Langerhans cell histiocytosis, formerly known as histiocytosis X, is
      characterised by clonal proliferation of pathologic cells resembling Langerhans
      cells. Langerhans cell histiocytosis is commonly localised in the bones of the
      skull or in the skin; however, a great variety of foci has been described. CASE:
      A general practitioner referred a 25-year-old man to the neurologist because of
      progressive pain in the neck that had arisen spontaneously. The pain had become
      so severe over a period of 3 weeks that he had had to support his head with both
      hands to ease it. Chiropractic treatment had resulted in a worsening of the
      symptoms. On physical examination, two pathologically enlarged lymph nodes were
      palpable on the left side of the neck. CT, MRI and PET scans revealed an
      osteolytic lesion at the site of the dens axis (C2). Immunohistochemistry of the
      lymph node demonstrated positive staining for CD1a and S100, characteristic of
      Langerhans cell histiocytosis. The patient was treated with chemotherapy and
      osteosynthesis of the C1-C2-C3 vertebrae; he was able to return to work after 9
      months. CONCLUSION: Langerhans cell histiocytosis is an extremely rare condition;
      its diagnosis is often missed or made at a later time. The golden diagnostic
      standard is histopathological analysis of the abnormality. The condition's
      prognosis is related to its extent. Its localisation in the dens axis has not
      been previously described.

PMID- 21939567
TI  - [Hip resurfacing in patients under 55 years of age].
AB  - Hip resurfacing arthroplasty was introduced as an alternative to the conventional
      total hip arthroplasty which had shown suboptimal results in younger patients.
      Application of the resurfacing technique in younger patients has increased over
      the last few years. To date, no randomized controlled trials with a minimum
      follow-up span of 10 years comparing hip resurfacing to conventional hip
      replacement have been conducted in patients under 55 years of age. Australian and
      English hip registries demonstrate high revision rates after 5 years for some
      brands of resurfacing implants. In addition to these disappointing revision
      rates, the complication of aseptic lymphocytic vasculitis caused by metal
      particles evoking a local tissue reaction has been increasingly reported. The
      resurfacing procedure recently received some negative media attention in the
      Netherlands, leading to confusion among patients. In order to ease patient
      doubts, it is important to correctly inform them as to the type of implant used,
      for example, by means of the website or an information card.

PMID- 21939568
TI  - [Evaluation of diagnosis and therapy of Staphylococcus aureus bacteraemia:
      recommended minimum treatment duration of 2 weeks not always met].
AB  - OBJECTIVE: Bacteraemia caused by Staphylococcus aureus (SA bacteraemia) can run a
      relatively mild course, but can also be complicated by focal infections in bones,
      joints, soft tissue and the heart. The Infectious Disease Society of America
      (IDSA) advises a transoesophageal echocardiogram (TOE) be taken in each case of
      SA bacteraemia in order to rule out endocarditis, in addition to sampling blood
      for culture 2-3 days after the start of treatment. Both the IDSA and the Dutch
      Stichting Werkgroep Antibiotica Beleid (SWAB - Foundation for Antibiotic Policy
      Work Groups) recommend that patients with SA bacteraemia be treated intravenously
      for at least 14 days; longer if a complicated course is expected. We investigated
      whether SA bacteraemia was diagnosed and treated according to current guidelines.
      DESIGN: Retrospective cohort study METHOD: A case series of consecutive patients
      >= 18 years of age with SA bacteraemia was identified using the electronic
      microbiology registration system. RESULTS: A total of 93 patients were
      identified. Median follow-up duration was >= 3 months. Of the 81 patients who had
      survived one week after admission to the hospital, 41(60%) did not undergo TOE.
      Blood cultures on day 3 were performed in only 6 (6%) patients. Of the 79 (85%)
      patients who had survived the first two weeks of infection, 26 (33%) had been
      treated with intravenous antibiotics for less than 14 days. Recurrent SA
      bacteraemia occurred in 4 patients. CONCLUSION: In the majority of patients with
      SA bacteraemia, diagnostic work-up and duration of therapy did not comply with
      ISDA and SWAB guidelines.

PMID- 21939569
TI  - [Shoulder surgery using only regional anaesthesia].
AB  - Effective intra-operative anaesthesia and peri-operative analgesia are important
      aspects of patient care in orthopaedic surgery. The interscalene regional
      anaesthetic block technique, performed with the patient lying in a lateral
      decubitus position, is new for arthroscopic shoulder surgery conducted in the
      Netherlands. The combination of the interscalene block (without general
      anaesthesia) and the lateral decubitus position results in better peri-operative
      conditions for the patient. Better analgesia, increased patient satisfaction and
      fewer complications in comparison to general anaesthesia have been reported for
      these types of surgery.

PMID- 21939570
TI  - [A neonate with a skin rash post partum].
AB  - A term-born boy presented with a rash immediately post partum, consisting of
      erosions, crusts and a few vesicles. Skin biopsy showed dermal infiltration of
      S100 and CD1a immunopositive histiocytes. The diagnosis was 'congenital
      Langerhans cell histiocytosis of the skin'.

PMID- 21939571
TI  - [Sir John Charnley and total hip arthroplasty].
AB  - Sir John Charnley (1911-1982), pioneer of the total hip prosthesis, saved
      countless elderly people from immobility. During the Second World War he assisted
      Dudley Buxton, orthopaedic surgeon to the British armed forces in the Middle
      East, in developing new instruments and splints. After the war he first studied
      healing of bone fractures and the role of compression, and then completely
      dedicated himself to arthroplasty of the hip. Through countless experiments he
      found the optimal diameter for the head of the stainless steel prosthesis as well
      as the optimal polymer for the socket; he also advocated tight cementing of the
      shaft into the femur. Sir John Charnley received the Lasker Award in 1974 and was
      knighted in 1977.

PMID- 21939572
TI  - [Early case finding of dementia: not advisable].
AB  - In a recent review of 6 cross-sectional studies, the specificity of the diagnosis
      'dementia' was found to be high, but the sensitivity of mild dementia was low.
      The authors wrote that the problem of low sensitivity ought to be solved.
      However, there appears to be no problem as there is no effective intervention to
      prevent the worsening of dementia, and selective case finding in early stages
      carries the risk of false positive diagnoses.

PMID- 21939573
TI  - [Acute coronary syndrome in women below 60 years of age].
AB  - Women below 60 years of age with acute coronary syndrome (ACS) have higher in
      hospital and 1-year mortality rates than similarly aged men, despite the lower
      prevalence of obstructive coronary artery disease. When ACS occurs, gender
      differences in symptom presentation result in later recognition by female
      patients themselves and by their doctors. Women with ACS have relatively more
      pain in the neck, back and shoulders with concomitant vaso-vegetative symptoms,
      feelings of anxiety, fatigue, and dyspnoea in comparison with the classical chest
      pain syndrome that is more prevalent in men. At a younger age smoking and a
      positive family history are stronger risk factors for ACS in women than in men,
      and the use of oral contraceptives further elevates their risk.

PMID- 21939574
TI  - ['Steroid psychosis' during treatment for premature labour].
AB  - A 30-year-old woman, 33 weeks pregnant, without a significant psychiatric
      history, was admitted for treatment of premature labour. She was treated with
      betamethasone intramuscularly, with a total dose of 24 mg divided over 2 days,
      and nifedipine orally with beneficial effect on the contractions. However, within
      24 h after completion of tocolytic treatment, she developed a psychosis with
      delusions and hallucinations necessitating readmission, first to an obstetric
      ward, later to a psychiatric ward. At least part of this episode may be
      characterized as delirium. Eventually, she was treated with haloperidol. It is
      argued that her psychosis was caused by the corticosteroid, since psychiatric
      disturbance is a well-known complication of corticosteroid therapy. To our
      knowledge, psychosis during pregnancy as a result of treatment with
      corticosteroids has not been reported previously.

PMID- 21939575
TI  - Morning versus afternoon cutting time of Berseem clover (Trifolium alexandrinum
      L.) affects feed intake, milk yield and composition in Girgentana goats.
AB  - Twenty lactating Girgentana goats were used to evaluate the effect of morning v.
      afternoon cutting time of Berseem clover (Trifolium alexandrinum L.) on feed
      intake, milk yield and milk composition. Goats were randomly divided into two
      groups of ten animals, receiving 10 kg of fresh Berseem clover cut at 9.00 (AM
      group) or 16.00 (PM group), respectively; 500 g of concentrate was given
      individually to goats before offering forage. Feed intake increased (P<0.01) in
      the PM group (30.5 v. 25.3 g dry matter/kg body weight), associated with the
      different nutrient content of diets: lower crude protein but higher dry matter,
      neutral detergent fibre, water soluble carbohydrates (WSC) and total fatty acids
      in the PM-harvested forage. Milk production, protein and casein content were
      higher (P<0.05) in the PM group (1415 g/d, 3.25% and 2.42% v. 1277 g/d, 3.15% and
      2.33%, respectively), whereas no differences between groups were detected for
      milk fat, lactose or urea content. Body weight slowly decreased from the start to
      the end of the experiment, without differences between groups. This study showed
      an important milk yield responses in Girgentana goats offered afternoon-cut
      compared with morning-cut Berseem clover, due to a marked increase in WSC in the
      afternoon-cut forage.

PMID- 21939576
TI  - Milk yield and somatic cell count during the following lactation after selective
      treatment of cows at dry-off.
AB  - Selective dry cow therapy (SDCT) has received increasing attention in recent
      years owing to global concerns over agricultural use of antimicrobial drugs and
      development of antimicrobial resistance. The objective of this study was to
      evaluate the effect of SDCT on milk yield and somatic cell count (SCC) in dairy
      herds in the USA. Cows in four Ohio dairy herds were categorized into two groups
      (low-SCC and high-SCC) at dry-off based on their SCC and clinical mastitis (CM)
      history during the lactation preceding the dry-off. Low-SCC cows were randomly
      assigned to receive or not to receive intramammary antibiotics at dry-off. Milk
      yield and SCC of these cows during the following lactation were compared using
      linear mixed effects models, adjusting for parity, calving season, stage of
      lactation, previous lactation milk yield and herd. Milk yield of untreated and
      treated low-SCC cows at dry-off did not differ significantly during the following
      lactation. Overall, treated low-SCC cows had 16% lower SCC (approximately 35 000
      cells/ml, P = 0.0267) than the untreated cows during the following lactation;
      however, the effect was variable in different herds. Moreover the impact of
      treatment, or the lack thereof, on milk yield varied considerably between herds.
      The results suggested that in some herds treating all cows at dry-off may be
      beneficial while in other herds leaving healthy cows without antibiotic dry cow
      treatment has no negative impact on milk yield or milk quality (SCC), and in
      fact, may be beneficial. Further studies are needed to identify characteristics
      of herds where treating all cows routinely at dry-off may be needed for
      maintaining good udder health and where switching to selective treatment of cows
      at dry-off would be the optimal approach to achieve best results.

PMID- 21939577
TI  - Optimizing the fluorometric beta-glucuronidase assay in ruminant milk for a more
      precise determination of mastitis.
AB  - Activity of the enzyme beta-glucuronidase (EC 3.2.1.31) is found in milk from
      ruminants with mastitis. However, the use of this enzymic activity as an
      indicator of mastitis has gained little attention possibly because of its low
      activity when compared with other mastitis indicators. The determination may
      therefore be less precise and the analytical procedure very time consuming and
      labour intensive. The present study optimized the fluorometric determination of
      the beta-glucuronidase activity with respect to substrate concentration, pH,
      incubation time etc., validated the assay, and developed it into large scale
      analyses. The assay performance is satisfactory regarding precision, linearity
      etc., and it appears comparable to analogous fluorometric assays for mastitis
      indicators in milk. From a local dairy herd, 825 milk samples were analysed for
      potential mastitis indicators, i.e. beta-glucuronidase, lactate dehydrogenase
      (LDH), alkaline phosphatase (AP), and N-acetyl-beta-d-glucosaminidase (NAGase)
      activity, and for somatic cell counts (SCC) and the variables were compared.
      Activity of beta-glucuronidase was moderately but significantly correlated to SCC
      (r=0.21; n=768) as well as the other mentioned variables (r=0.25-0.43; n=825).
      Simple indices based on beta-glucuronidase and LDH or NAGase activity were tested
      as indicators of mastitis (SCC), but were not found to improve the diagnostic
      value. Future studies may further verify whether beta-glucuronidase can compete
      with well-established indicators of mastitis in cows such as LDH or NAGase as
      well as determine whether beta-glucuronidase activity, in combination with other
      indicators of mastitis, has an advantage. Nineteen milk samples from subclinical
      and latent cases of mastitis (individual quarters) were identified for specific
      pathogens (PCR method) and measured for beta-glucuronidase activity. The activity
      was tested at four different pH levels (5.5, 6.0, 6.5 and 7.0) in order to
      investigate the possibility of discrimination between pathogens. However, all
      milk samples (strains of pathogens) had the same pH optimum for beta
      glucuronidase activity; this may indicate that enzymic activity from mammary
      tissue and leucocytes dominates over enzyme activity from bacterial cells.

PMID- 21939578
TI  - Association between covariates and disease occurrence in the presence of
      diagnostic error.
AB  - Identification of covariates associated with disease is a key part of
      epidemiological research. Yet, while adjustment for imperfect diagnostic accuracy
      is well established when estimating disease prevalence, similar adjustment when
      estimating covariate effects is far less common, although of important practical
      relevance due to the sensitivity of such analyses to misclassification error.
      Case-study data exploring evidence for seasonal differences in Salmonella
      prevalence using serological testing is presented, in addition simulated data
      with known properties are analysed. It is demonstrated that: (i) adjusting for
      misclassification error in models comprising continuous covariates can have a
      very substantial impact on the resulting conclusions which can then be drawn from
      any analyses; and (ii) incorporating prior knowledge through Bayesian estimation
      can provide potentially more informative assessments of covariates while removing
      the assumption of perfect diagnostic accuracy. The method presented is widely
      applicable and easily generalized to many types of epidemiological studies.

PMID- 21939579
TI  - Variants of Vibrio cholerae O1 El Tor from Zambia showed new genotypes of ctxB.

PMID- 21939581
TI  - Sex differences in infant mortality in Spitalfields, London, 1750-1839.
AB  - This study examines sex differences in infant mortality in Spitalfields, London,
      and the estimated contribution of endogenous and exogenous factors to neonatal
      and infant mortality using the biometric model from 1750 to 1839. There was a
      marked decline in the risk of death during infancy and the neonatal period for
      both sexes during the study period. There was significant excess male infant
      mortality compared with that of females in the 1750-59 cohort, estimated from
      baptism and burial registers, but not in later cohorts. Similarly, males had
      higher neonatal mortality rates than females in 1750-59 but not in later cohorts.
      Biometric analyses suggest that the observed decrease in neonatal mortality in
      both sexes was caused by a reduction in both endogenous and exogenous causes of
      death. The contribution of maternal health and breast-feeding practices to the
      observed patterns of mortality is discussed in the light of available evidence.

PMID- 21939582
TI  - A functional account of verb use in the early stages of English multiword
      development.
AB  - The present study investigates flexibility of verb use in the early stages of
      English multiword development, and its relationship with patterns attested in the
      input. The data is taken from a case study of a monolingual English-speaking boy
      aged 2 ; 5-2 ; 9 and his mother while engaged in daily activities in the home.
      Data were coded according to Halliday's (1975) functional system. The findings
      suggest that early multiword verb use is functionally restricted and closely tied
      to verb use in the input.

PMID- 21939583
TI  - One hundred years of railway disasters and recent trends.
AB  - INTRODUCTION: Globally, railway transport is increasing steadily. Despite the
      adoption of diverse safety systems, major railway incidents continue to occur.
      Higher speeds and increased passenger traffic are factors that influence the risk
      of mass-casualty incidents and make railway crashes a reality that merits
      extensive planning and training. METHODS: Data on railway disasters were obtained
      from the Centre for Research on the Epidemiology of Disasters (CRED), which
      maintains the Emergency Events Database (EM-DAT). This descriptive study consists
      of 529 railway disasters (>=10 killed and/or >=100 non- fatally injured) from
      1910 through 2009. RESULTS: The number of railway disasters, people killed, and
      non-fatally injured, has increased throughout the last hundred years-particularly
      during the last four decades (1970-2009), when 88% of all disasters occurred. In
      the mid-20th century, a shift occurred, resulting in more people being non
      fatally injured than fatally injured. During 1970-2009, 74% of all railway
      disasters occurred in Asia, Africa, and South and Central America, combined. The
      remaining 26% occurred in Europe, North America, and Oceania, combined. Since
      1980, railway disasters have increased, especially in Asia and Africa, while
      Europe has had a decrease in railway disasters. The number killed per disaster
      (1970-2009) was highest in Africa (n = 55), followed by South and Central America
      (n = 47), and Asia (n = 44). The rate was lowest in North America (n = 10) and
      Europe (n = 29). On average, the number of non-fatal injuries per disaster was
      two to three times the number of fatalities, however, in the African countries
      (except South Africa) the relation was closer to 1:1, which correlates to the
      relation found in more developed countries during the mid-20th century. The total
      losses (non-fatally and fatally injured) per disaster has shown a slight
      decreasing trend. CONCLUSIONS: Despite extensive crash avoidance and injury
      reduction safety systems, railway crashes occur on all continents, indicating
      that this type of incident must be accounted for in disaster planning and
      training. Better developed safety, crashworthiness, and rescue resources in North
      America and Europe may be factors explaining why the number of crashes and losses
      has stabilized and why the average number of people killed per disaster is lowest
      on these continents.

PMID- 21939584
TI  - The effects of dietary non-starch polysaccharides on Ascaridia galli infection in
      grower layers.
AB  - This study examined whether Ascaridia galli infection can be controlled by
      dietary non-starch polysaccharides (NSP) in chickens. One-day-old chicks were fed
      either a basal diet (CON) or CON plus insoluble NSP (I-NSP), or CON plus soluble
      NSP (S-NSP) for 11 weeks. Three weeks later, birds from half of each feeding
      group were inoculated with 250 embryonated eggs of A. galli, and slaughtered 8
      weeks post-infection to determine worm counts. Both NSP diets, particularly S
      NSP, increased prevalence of infection (P<0.05) and worm burden (roughly +50%) of
      the birds (P<0.001). A. galli infection caused a less efficient (P=0.013) feed
      utilization for body weight gain (BWG) resulting in lower body weights (P<0.001)
      irrespective of type of diet consumed. NSP-fed birds, particularly those on I
      NSP, consumed more (+8%) feed per unit BWG and showed retarded (P<0.001) BW
      development compared to CON-fed birds. Intracaecal pH was lowered by S-NSP
      (P<0.05). Both NSP diets increased the volatile fatty acids pool size in caeca
      (P<0.001) with S-NSP exerting a greater effect (+46%) than I-NSP (+24%). It is
      concluded that both NSPs supplemented diets alter gastrointestinal environment in
      favour of the nematode establishment, and thus have no potential for controlling
      A. galli infection in chickens.

PMID- 21939585
TI  - A novel triazolic naphthofuranquinone induces autophagy in reservosomes and
      impairment of mitosis in Trypanosoma cruzi.
AB  - Chagas' disease, caused by the protozoan Trypanosoma cruzi, represents a serious
      health problem in Latin America, and the available chemotherapy, which is based
      on 2 nitro-derivatives, is not satisfactory. In folk medicine, natural products
      including naphthoquinones have been employed for the treatment of different
      parasitic diseases. In the pursuit of alternative drugs for Chagas' disease, we
      investigated the mechanism of action of the triazolic naphthoquinone (TN; 2,2
      dimethyl-3-(4-phenyl-1H-1,2,3-triazol-1-yl)-2,3-dihydronaphtho[1,2-b]furan-4,5
      dione), which is the most active compound against T. cruzi trypomastigotes among
      a series of naphthofuranquinones. TN was active against the 3 parasite forms
      producing a dose-dependent inhibitory effect. In epimastigotes, TN induced
      reservosome disruption, flagellar blebbing, Golgi disorganization, the presence
      of cytosolic concentric membrane structures and abnormal multiflagellar
      parasites. The treatment also led to the appearance of well-developed endoplasmic
      reticulum profiles surrounding organelles that associated with an increase in
      monodansylcadaverine labelling, suggesting autophagy as part of the TN mechanism
      of action. Interestingly, no ultrastructural damage was detected in the
      mitochondria of naphthoquinone-treated epimastigotes. Flow cytometric analysis
      demonstrated an impairment of mitosis, an increase in ROS production and the
      maintenance of mitochondrial membrane potential. TN could be a good starting
      point in the investigation of a chemotherapeutic approach for the treatment of
      Chagas' disease.

PMID- 21939586
TI  - Identification of a gene cluster for cell-surface genes of the SRS superfamily in
      Neospora caninum and characterization of the novel SRS9 gene.
AB  - Here we present the detection of a gene cluster for Neospora caninum surface
      genes, similar to the Toxoplasma gondii SRS9 locus, and the cloning and
      characterization of the NcSRS9 gene. PCR genome walking, using NcBSR4 gene as a
      framework, allows the identification, upstream NcBSR4, of 2 sequences homologous
      to the SRS5 and the Ubiquinol-cytochrome C reductase genes and, downstream
      NcBSR4, of an ORF of 1191 bp coding for a 396-amino acid polypeptide with 59%
      similarity to the TgSRS9 antigen. A putative 39-residue signal peptide was found
      at the NH2-terminus followed by a hydrophilic region, and a potential site for a
      glycosylphosphatidylinositol anchor at the COOH-terminus. A recombinant NcSRS9
      protein was produced and was recognized on a Western blot by a low proportion of
      sera from a panel of naturally infected cows and calves. In addition, Western
      blot analysis using polyclonal anti-rNcSRS9 revealed stage-specific expression of
      NcSRS9 in bradyzoites but not in tachyzoites, and immunohistochemistry on brain
      from a congenitally infected calf showed NcSRS9 recognition in bradyzoites
      contained in tissue cysts. However, bradyzoite-specific expression of NcSRS9
      could not be proven by immunofluorescence on bradyzoites obtained in vitro and RT
      PCR analysis showed no significant variations of NcSRS9 transcripts during in
      vitro tachyzoite-bradyzoite switch, probably due to incomplete maturity of in
      vitro bradyzoites. Initial characterization of NcSRS9 in this study may lead to
      further studies for a better understanding of N. caninum persistence.

PMID- 21939587
TI  - PXRF, MU-XRF, vacuum MU-XRF, and EPMA analysis of Email Champleve objects present
      in Belgian museums.
AB  - The enamel of 20 Email Champleve objects dating between the 12th and 19th
      centuries was investigated by means of microscopic and portable X-ray
      fluorescence analysis (MU-XRF and PXRF). Seven of these objects were microsampled
      and the fragments were analyzed with electron probe microanalysis (EPMA) and
      vacuum MU-XRF to obtain quantitative data about the composition of the glass used
      to produce these enameled objects. As a result of the evolution of the raw
      materials employed to produce the base glass, three different compositional
      groups could be discriminated. The first group consisted of soda-lime-silica
      glass with a sodium source of mineral origin (with low K content) that was
      opacified by addition of calcium antimonate crystals. This type of glass was only
      used in objects made in the 12th century. Email Champleve objects from the
      beginning of the 13th century onward were enameled with soda-lime-silica glass
      with a sodium source of vegetal origin. This type of glass, which has a higher
      potassium content, was opacified with SnO2 crystals. The glass used for 19th
      century Email Champleve artifacts was produced with synthetic and purified
      components resulting in a different chemical composition compared to the other
      groups. Although the four analytical techniques employed in this study have their
      own specific characteristics, they were all found to be suitable for classifying
      the objects into the different chronological categories.

PMID- 21939588
TI  - Mood stabilizer lithium inhibits amphetamine-increased 4-hydroxynonenal-protein
      adducts in rat frontal cortex.
AB  - Recent studies indicate that bipolar disorder is associated with mitochondrial
      dysfunction and oxidative stress. Previous studies in our laboratory have shown
      that the mood stabilizer lithium inhibits oxidative stress. The alpha,beta
      unsaturated aldehyde 4-hydroxy-2-nonenal (4-HNE), a major product of lipid
      peroxidation, is able to exert cytotoxicity and disturb cellular function by
      forming protein adducts. The purpose of this study is to determine whether
      chronic lithium treatment prevents 4-HNE-protein adduction in an amphetamine
      induced hyperactive mania-like model. We found that repeated amphetamine
      stimulation significantly induced hyperactive behaviour, decreased activities of
      mitochondrial complexes I and III, and increased 4-HNE-protein adducts in rat
      frontal cortex, and that chronic lithium treatment inhibited both amphetamine
      induced hyperactivity and 4-HNE-protein adduction. Monoamine neurotransmitters
      are involved in the aetiology and pathology of bipolar disorder and other
      psychiatric diseases, and also contribute significantly to amphetamine-induced
      behavioural effects. Vesicular monoamine transporter 2 (VMAT2) is critical in
      packaging monoamine neurotransmitters. We found that 4-HNE can form protein
      adducts with VMAT2. Repeated amphetamine stimulation significantly increased 4
      HNE-VMAT2 adducts, while chronic lithium treatment reduced amphetamine-increased
      4-HNE-VMAT2 adducts in rat frontal cortex. Our findings suggest that chronic
      lithium treatment may inhibit amphetamine-induced hyperactive mania-like
      behaviour by preventing 4-HNE-VMAT2 adduction. This finding also indicates that
      prevention of 4-HNE-VMAT2 adduction may contribute in part to the pharmacological
      action of lithium for the treatment of bipolar disorder.

PMID- 21939589
TI  - Varenicline decreases nicotine self-administration and cue-induced reinstatement
      of nicotine-seeking behaviour in rats when a long pretreatment time is used.
AB  - Effects of varenicline (Champix), a nicotinic partial agonist, were evaluated on
      subjective effects of nicotine (drug discrimination), motivation for nicotine
      taking (progressive-ratio schedule of intravenous nicotine self-administration)
      and reinstatement (cue-induced reinstatement of previously extinguished nicotine
      seeking behaviour). Effects on motor performance were assessed in rats trained to
      discriminate nicotine (0.4 mg/kg) from saline under a fixed-ratio (FR 10)
      schedule of food delivery and in rats trained to respond for food under a
      progressive-ratio schedule. At short pretreatment times (5-40 min), varenicline
      produced full or high levels of partial generalization to nicotine's
      discriminative-stimulus effects and disrupted responding for food, while there
      were low levels of partial generalization and no disruption of responding for
      food at 2- or 4-h pretreatment times. Varenicline (1 and 3 mg/kg, 2-h
      pretreatment time) enhanced discrimination of low doses of nicotine and to a
      small extent decreased discrimination of the training dose of nicotine. It also
      dose-dependently decreased nicotine-taking behaviour, but had no effect on food
      taking behaviour under progressive-ratio schedules. Finally, varenicline
      significantly reduced the ability of a nicotine-associated cue to reinstate
      extinguished nicotine-seeking behaviour. The ability of varenicline to reduce
      both nicotine-taking and nicotine-seeking behaviour can contribute to its
      relatively high efficacy in treating human smokers.

PMID- 21939590
TI  - Preparing dossiers: strength of the evidence and problems of proof.
AB  - In Europe, for authorisation of a health claim, applicants must follow the
      procedures in the legislation and in the guidelines for submission of a dossier
      set out by the European Food Safety Authority. The Functional Foods in Europe
      (FUFOSE) and Process for the Assessment of Scientific Support for Claims on Foods
      (PASSCLAIM) projects underpinned the laws and provided criteria against which the
      quality of the totality of the available data could be judged. Whereas the
      regulations and PASSCLAIM require an assessment of the extent to which cause and
      effect can be demonstrated between a food category, a food or constituent and a
      health benefit, the European Food Safety Authority requires conclusive evidence
      of cause and effect. This latter standard of proof and a focus on randomised
      controlled trials done on isolated components and using validated physiological
      biomarkers may not always be appropriate to assess nutrition science. The aims of
      this paper are to address the strengths and weaknesses of different sources of
      evidence that contribute to the totality of the available data, to undertake a
      critical examination of the application of a drug-like assessment model in
      evidence-based nutrition and to encourage research on new biomarkers of health
      and homeostatic adaptability. There is a need for (a) a robust and pragmatic
      scientific framework for assessing the strength, consistency and biological
      plausibility of the evidence, and (b) consumer understanding research on claims
      that use qualifying language and/or graphics to reflect the weight of evidence.
      Such scientific, policy and communication approaches are proportionate and could
      help stimulate academic research, promote fair trade and product innovation and
      contribute to consumer education about food and health.

PMID- 21939592
TI  - Categories versus dimensions in personality and psychopathology: a quantitative
      review of taxometric research.
AB  - Taxometric research methods were developed by Paul Meehl and colleagues to
      distinguish between categorical and dimensional models of latent variables. We
      have conducted a comprehensive review of published taxometric research that
      included 177 articles, 311 distinct findings and a combined sample of 533 377
      participants. Multilevel logistic regression analyses have examined the
      methodological and substantive variables associated with taxonic (categorical)
      findings. Although 38.9% of findings were taxonic, these findings were much less
      frequent in more recent and methodologically stronger studies, and in those
      reporting comparative fit indices based on simulated comparison data. When these
      and other possible confounds were statistically controlled, the true prevalence
      of taxonic findings was estimated at 14%. The domains of normal personality, mood
      disorders, anxiety disorders, eating disorders, externalizing disorders, and
      personality disorders (PDs) other than schizotypal yielded little persuasive
      evidence of taxa. Promising but still not definitive evidence of psychological
      taxa was confined to the domains of schizotypy, substance use disorders and
      autism. This review indicates that most latent variables of interest to
      psychiatrists and personality and clinical psychologists are dimensional, and
      that many influential taxonic findings of early taxometric research are likely to
      be spurious.

PMID- 21939591
TI  - Effective elements of cognitive behaviour therapy for psychosis: results of a
      novel type of subgroup analysis based on principal stratification.
AB  - BACKGROUND: Meta-analyses show that cognitive behaviour therapy for psychosis
      (CBT-P) improves distressing positive symptoms. However, it is a complex
      intervention involving a range of techniques. No previous study has assessed the
      delivery of the different elements of treatment and their effect on outcome. Our
      aim was to assess the differential effect of type of treatment delivered on the
      effectiveness of CBT-P, using novel statistical methodology. METHOD: The
      Psychological Prevention of Relapse in Psychosis (PRP) trial was a multi-centre
      randomized controlled trial (RCT) that compared CBT-P with treatment as usual
      (TAU). Therapy was manualized, and detailed evaluations of therapy delivery and
      client engagement were made. Follow-up assessments were made at 12 and 24 months.
      In a planned analysis, we applied principal stratification (involving structural
      equation modelling with finite mixtures) to estimate intention-to-treat (ITT)
      effects for subgroups of participants, defined by qualitative and quantitative
      differences in receipt of therapy, while maintaining the constraints of
      randomization. RESULTS: Consistent delivery of full therapy, including specific
      cognitive and behavioural techniques, was associated with clinically and
      statistically significant increases in months in remission, and decreases in
      psychotic and affective symptoms. Delivery of partial therapy involving
      engagement and assessment was not effective. CONCLUSIONS: Our analyses suggest
      that CBT-P is of significant benefit on multiple outcomes to patients able to
      engage in the full range of therapy procedures. The novel statistical methods
      illustrated in this report have general application to the evaluation of
      heterogeneity in the effects of treatment.

PMID- 21939593
TI  - Isomer-specific effects of conjugated linoleic acid on blood pressure, adipocyte
      size and function.
AB  - Obesity-related hypertension may be caused by activation of the local adipose
      tissue renin-angiotensin system, resulting in exaggerated production of the
      vasoconstrictor angiotensin II. Additionally, secretion of adiponectin from
      adipose tissue, which prevents endothelial dysfunction, is altered in obesity.
      Consumption of conjugated linoleic acid (CLA) has been shown to modulate cytokine
      release from adipocytes and positively influence blood pressure in younger rats,
      but its physiological actions in older models with established hypertension and
      isomer-specific effects on adipocyte size remain to be determined. Therefore, we
      investigated the effects of CLA isomers on adipocyte size in relation to blood
      pressure and adipokine production by hypertrophic adipocytes in older fa/fa
      Zucker rats with established hypertension. fa/fa Zucker rats were fed with
      cis(c)9, trans(t)11-CLA or t10, c12-CLA isomers for 8 weeks and compared with
      lean and obese rats fed with the control diet. Blood pressure and adipocyte size
      were subsequently measured. Collagenase-isolated adipocytes were size-separated
      and angiotensinogen and adiponectin protein levels quantified by Western
      blotting. The t10, c12-CLA group had reduced blood pressure, fewer large
      adipocytes and increased serum adiponectin. Angiotensinogen was present at higher
      levels in the large adipocytes, whereas the converse was observed for
      adiponectin. The beneficial effects of the t10, c12-CLA isomer on blood pressure
      and adipocyte size in vivo may be due to its ability to reduce the number of
      large adipocytes, which alters the levels of vasoactive molecules secreted from
      adipose tissue.

PMID- 21939594
TI  - A design of experiments for statistically predicting risk of adverse health
      effects on drivers exposed to vertical vibrations.
AB  - An injury risk factor (IRF), which indicates the risk of adverse health effect to
      lumbar rachis arising from mechanical vibrations, is developed. Experiments have
      been conducted that consider acceleration levels at the seat of drivers, posture,
      morphology, density, damping rate and body mass as independent variables. A
      parametric finite-element model of the lumbar rachis has been generated. It is
      shown that the IRF increases with ageing and an IRF of 30% is proposed as a
      threshold for fatigue purposes. This level is reached if a peak acceleration
      level greater than 3 m/s2 is applied to a light (55 kg) and an old driver with a
      low bone density and a damping rate of 20%. This vibration threshold must be
      reduced to 2.7 m/s2 if the driver?s weight increases to 75 kg and to 2 m/s2 if
      the driver is heavy (98 kg).

PMID- 21939595
TI  - Development and validation of a numerical prediction model to estimate the
      annoyance condition at the operation station of compact loaders.
AB  - This paper describes the results of a study aimed at developing and validating a
      prediction model to assess the annoyance conditions at the operator station of
      compact loaders by using noise signal objective parameters only. For this
      purpose, binaural measurements were carried out on 41 compact loaders, both in
      stationary and real working conditions. The 62 binaural noise recordings were
      objectively analysed in terms of acoustic and psychoacoustic parameters and then
      divided into 9 groups and used in specific jury tests to obtain the subjective
      annoyance scores. Finally, multiple regression technique was applied to the first
      6 groups of noise stimuli to develop the model while the remaining groups were
      used to validate it.

PMID- 21939596
TI  - Examining the effectiveness of anti-vibration gloves with a neural network.
AB  - Whether anti-vibration gloves are effective in protecting against vibrations
      depends not only on the materials they are made of, but also on the parameters of
      the source of vibration. Depending on those parameters, the effectiveness of the
      same means of protection may be radically different. This article presents a
      methodology of using a neural network to test anti-vibration gloves. A network
      can map gloves in various conditions, i.e., for vibrations of various amplitudes
      and spectra, and for various forces exerted by the worker on a tool. Real,
      measured vibration signals produced by different tools were used in training a
      neural network. The results presented in this article prove that real properties
      of gloves are accurately represented by their models developed as a result of
      training a neural network.

PMID- 21939597
TI  - Effect of musician's earplugs on sound level and spectrum during musical
      performances.
AB  - In this study, change in A-weighted and 1/3 octave sound pressure levels (SPLs)
      was used to assess the influence of wearing earplugs by musicians on their
      musical performances. Seven soloists and 3 music assembles performed 4 pieces of
      music with musician's earplugs donned and doffed. They used silicon custom
      moulded earplugs with acoustic filters designed to attenuate sound by 9, 15 or 25
      dB. Results showed that the use of earplugs affected the sound level and the
      spectrum of played sounds. This effect was the greatest for brass players. The
      difference between SPLs in high-frequency 1/3-octave bands and A-weighted SPLs
      with and without earplugs exceeded 5 and 15 dB, respectively. Similar changes for
      woodwind, percussion and string instruments were less noticeable than for brass
      instruments; they were more than 5 dB for 1/3-octave spectra and no more than 2
      dB for A-weighted SPL.

PMID- 21939598
TI  - Evaluation of sound exposure and risk of hearing impairment in orchestral
      musicians.
AB  - This study aimed to assess exposure to sound and the risk of noise-induced
      hearing loss (NIHL) in orchestral musicians. Sound pressure level was measured in
      1 opera and 3 symphony orchestras; questionnaires were filled in. On the basis of
      that data, the risk of NIHL was assessed according to Standard No. ISO 1999:1990.
      Classical orchestral musicians are usually exposed to sound at equivalent
      continuous A-weighted sound pressure levels of 81?90 dB (10th?90th percentiles),
      for 20?45 h (10th?90th percentiles) per week. Occupational exposure to such sound
      levels over 40 years of employment might cause hearing loss (expressed as a mean
      hearing threshold level at 2, 3, 4 kHz exceeding 35 dB) of up to 26%. Playing the
      horn, trumpet, tuba and percussion carries the highest risk (over 20%).

PMID- 21939599
TI  - Estimating surface acoustic impedance with the inverse method.
AB  - Sound field parameters are predicted with numerical methods in sound control
      systems, in acoustic designs of building and in sound field simulations. Those
      methods define the acoustic properties of surfaces, such as sound absorption
      coefficients or acoustic impedance, to determine boundary conditions. Several in
      situ measurement techniques were developed; one of them uses 2 microphones to
      measure direct and reflected sound over a planar test surface. Another approach
      is used in the inverse boundary elements method, in which estimating acoustic
      impedance of a surface is expressed as an inverse boundary problem. The boundary
      values can be found from multipoint sound pressure measurements in the interior
      of a room. This method can be applied to arbitrarily-shaped surfaces. This
      investigation is part of a research programme on using inverse methods in
      industrial room acoustics.

PMID- 21939600
TI  - A global index of acoustic assessment of machines-results of experimental and
      simulation tests.
AB  - A global index of machines was developed to assess noise emitted by machines and
      to predict noise levels at workstations. The global index is a function of
      several partial indices: sound power index, index of distance between the
      workstation and the machine, radiation directivity index, impulse and impact
      noise index and noise spectrum index. Tests were carried out to determine values
      of the global index for engine-generator; the inversion method for determining
      sound power level was used. It required modelling each tested generator with one
      omnidirectional substitute source. The partial indices and the global index were
      simulated, too. The results of the tests confirmed the correctness of the
      simulations.

PMID- 21939601
TI  - Noise generated by multiple-jet nozzles with conical profiles 287.
AB  - Conical multiple-jet nozzles, which reduce the risk of nozzle openings being
      blocked, are tested for their effectiveness in noise reduction. Nozzles with
      different exit spacings are tested. It is found that the multiple-jet design
      significantly decreases noise levels in the audible range by shifting emitted
      sound power to higher and ultrasonic frequencies. No significant difference in
      noise characteristics between exits distributed on a flat plane and beveled exits
      on a conical surface is observed. When the exits are more densely distributed,
      there is a trend of spectra shifting back toward the low frequency. This
      phenomenon is found to increase sound levels in a certain range of frequencies
      much lower than the peak one. Although this increase contributes little to the
      total emitted sound power, it is an important factor in determining the sound
      levels of audible noise.

PMID- 21939602
TI  - Noise variability in underground room and pillar coal mines.
AB  - Noise in an underground coal mine has dominant components generated mainly from 3
      sources: (a) continuous mining machines, (b) roof bolters, and (c) cars/vehicles
      used to transport personnel and/or coal. Each of these 3 noise sources also has a
      number of well-defined sub-sources with their own noise characteristics. Sound
      level meters were used to collect noise data in the form of instantaneous
      readings and also to check calibration of other sound measuring instruments. The
      most useful information was obtained from a spectrum analysis of continuous
      digital recordings of noise over time. This paper discusses the variability or
      dynamics of generated noise in both frequency and time domains in relation to
      several independent variables related to coal extraction and transportation
      processes.

PMID- 21939603
TI  - Problems of railway noise-a case study.
AB  - Under Directive 2002/49/EC relating to the assessment and management of
      environmental noise, all European countries are obliged to model their
      environmental noise levels in heavily populated areas. Some countries have their
      own national method, to predict noise but most have not created one yet. The
      recommendation for countries that do not have their own model is to use an
      interim method. The Dutch SRM II scheme is suggested for railways. In addition to
      the Dutch model, this paper describes and discusses 3 other national methods.
      Moreover, discrepancies between the HARMONOISE and IMAGINE projects are analysed.
      The results of rail traffic noise measurements are compared with national
      methods.

PMID- 21939604
TI  - Diagnosis and surgical treatment of solid pseudopapillary neoplasm of the
      pancreas: analysis of 24 cases.
AB  - BACKGROUND: Our aim was to summarize our experience with the diagnosis and
      surgical treatment of solid pseudopapillary neoplasm (SPN) of the pancreas to
      provide a reference for the management of this rare condition. METHODS: We
      collected and analyzed retrospective data on the clinical presentation,
      laboratory investigations, radiologic imaging, pathology and operative details of
      patients with SPN of the pancreas diagnosed between February 2001 and December
      2009. RESULTS: In all, 23 of 24 patients were women, and the mean age of all
      patients was 31 years. The most common clinical presentation was vague abdominal
      pain. Abdominal imaging showed solid or solid cystic masses in the pancreas,
      mostly in the tail or head of the gland. All patients were treated surgically.
      There were no postoperative deaths. After follow-up ranging from 4 to 109 months
      (median 68 mo), 20 of 22 patients who underwent curative resection were alive
      with no evidence of disease recurrence. Of the 2 patients with R1 resections, 1
      died 42 months after surgery, whereas the other underwent a second operation and
      was alive after 36 months' follow-up. CONCLUSION: Solid pseudopapillary neoplasm
      of the pancreas is a relatively indolent tumour. The initial diagnosis of SPN of
      the pancreas is suggested by radiologic imaging findings but should be considered
      in the context of clinical and histopathologic characteristics. We advocate for
      complete surgical resection once SPN is diagnosed.

PMID- 21939605
TI  - Postoperative recurrence of cystic hydatidosis.
AB  - BACKGROUND: Surgical management is the basic treatment for hydatid disease.
      Overall, the recurrence rate appears to be high (4.6%-22.0%). The purpose of this
      study was to report our results in the management of recurrent hydatid disease,
      evaluating the methods for identifying recurrence, prognostic factors and
      therapeutic options. METHODS: We retrospectively reviewed the medical records of
      patients who underwent surgery for cystic hydatidosis between 1970 and 2003.
      RESULTS: Of the 584 patients who underwent surgery during our study period,
      follow-up was complete for 484 (82.8%). Cysts recurred in 51 patients (8.7%).
      Abdominal ultrasonography and computed tomography appeared to be efficient for
      diagnosing recurrence. The 2 most important determinants for recurrence were
      minute spillage of the hydatid cyst and inadequate treatment owing to missing
      cysts or incomplete pericystectomy. All but 2 recurrences required surgery. There
      were 14 postoperative complications for a rate of 27.0%. Thirteen re-recurrences
      were observed in the follow-up of these patients and also required surgery.
      CONCLUSION: Avoidance of minute spillage of cyst contents and cautious removal of
      the parasite with as much of the pericyst as possible are fundamental objectives
      of primary-hydatid surgery. Conservative surgery (removal of the cyst contents
      plus partial pericystectomy with drainage when necessary) plus chemotherapy and
      local sterilization is suggested for both primary and secondary operations and
      appears to achieve satisfactory longterm results. Radical surgery (resection,
      cystopericystectomy) is preferred only in select patients.

PMID- 21939607
TI  - Pregnancy among residents enrolled in general surgery (PREGS): a survey of
      residents in a single Canadian training program.
AB  - BACKGROUND: Interest in general surgery has declined, and lack of adequate
      accommodation for pregnancy and parenting may be a deterrent. We explored
      resident experiences with these issues within a single general surgery program.
      METHODS: We surveyed residents enrolled in the University of British Columbia
      general surgery program from 1997 to 2009 using a Web-based survey tool.
      Information regarding demographics, pregnancy, postpartum issues and issues
      pertaining to maternity/parenting policies was obtained. We used the Student t
      test, Z test and Fisher exact test for statistical comparisons. RESULTS: Of the
      81 residents surveyed, 53 responded (65% response rate). There were fewer
      pregnancies during residency among female residents than among partners of male
      residents (PMRs; 9 pregnancies for 6 of 25 residents v. 23 pregnancies for 15 of
      28 PMRs, p = 0.002). One of 9 pregnancies among female residents and 5 of 23
      among PMRs ended in miscarriage (p > 0.99). Female residents and PMRs reported
      pregnancy-related complications with equal frequency. All female residents
      breastfed for at least 6 months; however, 67% (4 of 6) felt their resident role
      prevented them from breastfeeding as long as they would have liked. Most (5 of 6,
      83%) pursued a graduate degree or research during their "maternity leave." More
      than 50% of residents reported that their own workload increased because of a
      colleague's pregnancy. Many (36 of 53, 68%) were unaware of the existence of any
      maternity/parenting policy, and most were in favour of instituting such a policy.
      CONCLUSION: Resident mothers do not breastfeed for the desired duration, and
      precluding factors must be explored. Contingency plans are needed so colleagues
      are not overburdened when pregnant residents cannot perform clinical duties.
      General surgery programs must have a formal policy addressing these issues.

PMID- 21939606
TI  - Total pelvic exenteration for rectal cancer: outcomes and prognostic factors.
AB  - BACKGROUND: To perform complete resection of locally advanced and recurrent
      rectal carcinoma, total pelvic exenteration (TPE) may be attempted. We identified
      disease-related outcomes and prognostic factors. METHODS: We conducted a single
      centre review of patients who underwent TPE for rectal carcinoma over a 10-year
      period. RESULTS: We included 28 patients in our study. After a median follow-up
      of 35 months, 53.6% of patients were alive with no evidence of disease. The 3
      year actuarial disease-free and overall survival rates were 52.2% and 75.1%,
      respectively. On univariate analysis, recurrent disease, preoperative body mass
      index greater than 30 and lymphatic invasion were poor prognostic factors for
      disease-free survival, and only lymphatic invasion predicted overall survival.
      Additionally, multivariate analysis identified lymphatic invasion as an
      independent poor prognostic factor for disease-free survival in this patient
      population with locally advanced and recurrent rectal carcinoma. CONCLUSION:
      Despite the significant morbidity, TPE can provide long-term survival in patients
      with rectal carcinoma. Additionally, lymphatic invasion on final pathology was an
      independent prognostic factor for disease-free survival.

PMID- 21939608
TI  - How to assess a survey in surgery.

PMID- 21939609
TI  - An electronic clinic for arthroplasty follow-up: a pilot study.
AB  - BACKGROUND: Most outpatient orthopedic follow-up visits for patients who had
      total joint arthroplasty are routine among those with well-functioning implants.
      The technology and resources now exist to enable patient assessment without
      requiring attendance in hospital. We tested an electronic clinic for routine
      follow-up in a small cohort of arthroplasty patients. METHODS: We randomly
      assigned primary arthroplasty patients scheduled for routine annual outpatient
      review into 2 groups: group A completed a Web-based assessment 4 weeks after the
      clinical assessment, whereas group B completed the Web-based assessment first.
      Standard clinical questionnaires were included. We also collected radiographic
      data and information on assessment duration and cost. RESULTS: Forty patients
      participated in the study. The average age of participants was 58 years. There
      were 12 men and 8 women in each of the 2 groups. The average total time spent by
      patients on an outpatient visit was 115 minutes, compared with 52 minutes for the
      electronic assessment. Participants reported the electronic assessment to be more
      convenient and less costly. CONCLUSION: This pilot study supports the practical
      use of an electronic clinic for the follow-up of arthroplasty patients. Further
      studies examining the complex interaction of factors involved in patient clinics
      are needed.

PMID- 21939610
TI  - Neural correlates and predictive power of trait resilience in an acutely
      traumatized sample: a pilot investigation.
AB  - OBJECTIVE: Resilience refers to the ability to thrive despite adversity and is
      defined as a multidimensional phenomenon, spanning internal locus of control,
      sense of meaning, social problem-solving skills, and self-esteem. We aimed to
      investigate the predictive value of resilience for the development of
      posttraumatic stress disorder (PTSD) and to examine the neural correlates
      mediating the relationship between resilience and recovery from a traumatic event
      in acutely traumatized subjects. We hypothesized that resilience would mediate
      the relationship between childhood trauma and posttraumatic recovery. METHOD: We
      conducted a prospective study with 70 acutely traumatized subjects with DSM-IV
      PTSD recruited at the emergency department, assessing PTSD symptom severity at 3
      time points within the first 3 months posttrauma. Scores for childhood trauma as
      assessed with the Childhood Trauma Questionnaire and trait resilience as assessed
      with the Connor-Davidson Resilience Scale were used as predictors of symptom
      severity. A subsample of 12 subjects additionally underwent a functional 4 Tesla
      magnetic resonance imaging scan 2 to 4 months posttrauma. We employed the
      traumatic script-driven imagery paradigm to assess the correlations between trait
      resilience and blood oxygen level-dependent (BOLD) response. The study was
      conducted from 2003 to 2007. RESULTS: Resilience predicted PTSD symptom severity
      at 5 to 6 weeks (beta = -0.326, P = .01) as well as at 3 months (beta = -0.423, P
      = .003) posttrauma better than childhood trauma. Resilience essentially mediated
      the relationship between childhood trauma and posttraumatic adjustment.
      Resilience scores were positively correlated with BOLD signal strength in the
      right thalamus as well as the inferior and middle frontal gyri (Brodmann area
      47). CONCLUSIONS: This pilot investigation revealed a significant relationship
      between resilience and emotion regulation areas during trauma recall in an
      acutely traumatized sample. Resilience was established as a significant predictor
      of PTSD symptom severity and mediated the influence of childhood trauma on
      posttraumatic adjustment.

PMID- 21939611
TI  - Effect of second-generation antipsychotics on caregiver burden in Alzheimer's
      disease.
AB  - BACKGROUND: Alzheimer's disease (AD) imposes a severe burden upon patients and
      their caregivers. Severity of psychiatric symptoms and behavioral disturbances is
      an important determinant of caregivers' experience of burden. These symptoms may
      be improved with atypical antipsychotic treatment. OBJECTIVE: Data from the
      Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease
      (CATIE-AD) trial were used to evaluate the effect of atypical antipsychotics
      versus placebo on the experiences of caregivers of outpatients with AD. METHOD:
      We compared the effect of atypical antipsychotic drugs (olanzapine, risperidone,
      or quetiapine-considered together as a group) versus placebo on the experiences
      of caregivers of AD outpatients (diagnosed according to DSM-IV-TR). We also
      evaluated whether improvement in patients' psychiatric and behavioral symptoms
      mediated the relationship between drug treatment and caregiver burden. The CATIE
      AD trial, conducted from April 2001 through November 2004, included outpatients
      (mean age = 77.9 years [SD = 7.5 years]) in usual care settings and assessed
      treatment effectiveness over a 9-month period at 42 US sites. In a set of
      secondary analyses, data from CATIE-AD participants who had at least 1
      postbaseline outcome assessment and data from their caregivers were examined in
      an intention-to-treat (ITT) analysis (N = 361). A phase 1-only analysis was
      conducted including only observations while patients were receiving the initially
      randomized drug (N = 153). The Burden Interview, the Beck Depression Inventory,
      and the Neuropsychiatric Inventory (NPI) Caregiver Distress Scale were used to
      evaluate caregiver burden. RESULTS: In both ITT and phase 1-only analyses,
      caregivers of patients treated with second-generation antipsychotics scored
      significantly lower than caregivers of patients receiving placebo on both the
      Burden Interview (P = .0090) and the NPI Caregiver Distress Scale (P = .0209).
      These differences appeared to have been mediated by lower levels of agitation,
      hostility, and psychotic distortions. CONCLUSION: In AD patients with symptoms of
      psychosis, agitation, or aggressive behavior, medications can have a small but
      significant impact on caregiver burden.

PMID- 21939612
TI  - Time to treatment response in first-episode schizophrenia: should acute treatment
      trials last several months?
AB  - OBJECTIVE: Response patterns may differ between patients with first-episode and
      multiepisode schizophrenia. This analysis explored trial duration with first
      episode patients and asked whether early limited improvement predicts ultimate
      lack of treatment response with first-episode patients as it does with
      multiepisode patients. METHOD: One hundred twelve subjects (mean age = 23.3
      years, SD = 5.1 years) who presented between November 1998 and October 2004 with
      a first episode of psychosis and had a DSM-IV diagnosis of schizophrenia or
      schizophreniform or schizoaffective disorder were randomly assigned to treatment
      with olanzapine or risperidone for 16 weeks. Treatment response, the primary
      outcome measure, was defined as a rating of mild or better on all of the positive
      symptom items on the Schedule for Affective Disorders and Schizophrenia Change
      Version With Psychosis and Disorganization Items. Response rates were calculated
      for each study week. A logistic regression analysis examined the association
      between percentage reduction in symptom severity scores from baseline values at
      weeks 2, 4, or 8 and response by week 16. The study was conducted at The Zucker
      Hillside Hospital, Glen Oaks, New York and the Bronx-Lebanon Hospital Center,
      Bronx, New York. RESULTS: The estimated cumulative response rate was 39.59% (95%
      CI, 29.77%-49.41%) by week 8 and 65.19% (95% CI, 55.11%-75.27%) by week 16. The
      confidence intervals for estimated response at weeks 10, 12, 14, and 16 were not
      distinct. Response rates increased approximately 5 to 6 percentage points each 2
      week interval between week 10 and 16. Percentage reduction in symptom severity
      score at week 4 (but not 2 or 8) was associated (chi21 = 3.96; P < .05) with
      responder status at week 16 (odds ratio = 1.03; 95% CI, 1.00-1.05). However,
      receiver operating characteristic curves did not suggest any level of percentage
      symptom reduction that would be clinically useful as a predictor of response by
      week 16. CONCLUSIONS: Many first-episode patients respond between weeks 8 and 16
      of treatment with a single antipsychotic medication. Limited early symptom
      improvement does not identify those first-episode patients who will not improve
      with a full 16-week trial with enough accuracy to be clinically useful. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00000374.

PMID- 21939613
TI  - Efficacy of dose increase among nonresponders to low-dose aripiprazole
      augmentation in patients with inadequate response to antidepressant treatment: a
      randomized, double-blind, placebo-controlled, efficacy trial.
AB  - OBJECTIVE: To examine the efficacy of a dose increase of aripiprazole to 5 mg/d
      in subjects with major depressive disorder (MDD) who did not respond to 4 weeks
      of treatment with aripiprazole 2 mg/d in a randomized, double-blind, placebo
      controlled, parent study. METHOD: 221 Subjects with Structured Clinical Interview
      for DSM-IV Axis I Disorders-Patient Edition-diagnosed DSM-IV-TR MDD (mean +/- SD
      age, 45 +/- 11 years; 64% women) with inadequate antidepressant response were
      recruited from September 2008-July 2009 and randomized to 60 days of double-blind
      augmentation with either aripiprazole or placebo in two 30-day phases. The study
      was performed across 8 academic hospital sites and 14 nonacademic (private
      clinic) sites throughout the United States. Randomization in a 2:3:3 ratio per
      sequential parallel comparison design was drug/drug (aripiprazole 2 mg/d in phase
      1 and 5 mg/d in phase 2), placebo/placebo (placebo in both phases), and
      placebo/drug (placebo in phase 1 and aripiprazole 2 mg/d in phase 2). In phase 2,
      we examined efficacy of an aripiprazole dose increase to 5 mg/d in nonresponders
      to 2 mg/d by assessing response rates (>= 50% reduction in Montgomery-Asberg
      Depression Rating Scale [MADRS] score [primary outcome measure]) and score
      changes in MADRS, Quick Inventory of Depressive Symptomatology-Self-Report, 9
      item Patient Health Questionnaire (PHQ-9), the Clinical Global Impressions
      Severity of Illness (CGI-S) and -Improvement (CGI-I) scales, and patient-rated
      versions of the CGI-I and CGI-S scales. RESULTS: Response rate for aripiprazole 2
      mg/d in phase 1 was 18.5% (n/n = 10/54). Among 39 nonresponders who increased
      their dose to 5 mg/d, response rate was 12.8% (95% CI, 4.30%-27.43%), with
      significant overall mean +/- SD reductions in MADRS scores (-9.46 +/- 7.83 [95%
      CI, -12.00 to -6.92]; P < .0001), Symptoms Questionnaire Distress scores (19.51
      +/- 17.73 [95% CI, 13.60 to 25.43]; P < .0001), PHQ-9 scores (-7.92 +/- 5.92 [95%
      CI, -9.89 to -5.94]; P < .0001), and CGI-S scores (-0.86 +/- 0.86 [95% CI, -1.15
      to -0.58]; P < .0001). Differences in efficacy between drug and placebo groups
      were nonsignificant, however. Aripiprazole and placebo were well tolerated.
      CONCLUSIONS: Augmentation with aripiprazole 5 mg/d may provide only a modest
      additional benefit in patients who do not benefit from lower doses. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00683852.

PMID- 21939614
TI  - Meta-analysis of the effects of eicosapentaenoic acid (EPA) in clinical trials in
      depression.
AB  - OBJECTIVE: Randomized trials of omega-3 polyunsaturated fatty acid (PUFA)
      treatment for depression have differed in outcome. Recent meta-analyses ascribe
      discrepancies to differential effects of eicosapentaenoic acid (EPA) versus
      docosahexaenoic acid (DHA) and to diagnostic heterogeneity. This meta-analysis
      tests the hypothesis that EPA is the effective component in PUFA treatment of
      major depressive episodes. DATA SOURCES: PubMed/MeSH was searched for studies
      published in English from 1960 through June 2010 using the terms fish oils (MeSH)
      AND (depressive disorder [MeSH] OR bipolar depression) AND randomized controlled
      trial (publication type). The search was supplemented by manual bibliography
      review and examination of relevant review articles. STUDY SELECTION: The search
      yielded 15 trials involving 916 participants. Studies were included if they had a
      prospective, randomized, double-blinded, placebo-controlled study design; if
      depressive episode was the primary complaint (with or without comorbid medical
      conditions); if omega-3 PUFA supplements were administered; and if appropriate
      outcome measures were used to assess depressed mood. DATA EXTRACTION: Extracted
      data included study design, sample sizes, doses and percentages of EPA and DHA,
      mean ages, baseline and endpoint depression ratings and standard deviations for
      PUFA and placebo groups, and P values. The clinical outcome of interest was the
      standardized mean difference in the change from baseline to endpoint scores on a
      depression rating scale in subjects taking PUFA supplements versus subjects
      taking placebo. DATA SYNTHESIS: In a mixed-effect model, percentage of EPA in the
      supplements was the fixed-effect predictor, dichotomized into 2 groups: EPA < 60%
      or EPA >= 60% of the total EPA + DHA. Secondary analyses explored the relevance
      of treatment duration, age, and EPA dose. RESULTS: Supplements with EPA >= 60%
      showed benefit on standardized mean depression scores (effect size = 0.532; 95%
      CI, 0.277-0.733; t = 4.195; P < .001) versus supplements with EPA < 60% (effect
      size = -0.026; 95% CI, -0.200 to 0.148; t = -0.316; P = .756), with negligible
      contribution of random effects or heteroscedasticity and with no effects of
      treatment duration or age. Supplements with EPA < 60% were ineffective.
      Exploratory analyses supported a nonlinear model, with improvement determined by
      the dose of EPA in excess of DHA, within the range of 200 to 2,200 mg/d of EPA.
      CONCLUSIONS: Supplements containing EPA >= 60% of total EPA + DHA, in a dose
      range of 200 to 2,200 mg/d of EPA in excess of DHA, were effective against
      primary depression. Translational studies are needed to determine the mechanisms
      of EPA's therapeutic benefit.

PMID- 21939617
TI  - On the optimum probe in aberration corrected ADF-STEM.
AB  - New aberration correctors present new challenges in optimizing (minimizing) the
      probe size in the STEM (Scanning Transmission Electron Microscope). A small probe
      is important for high resolution imaging and analytical microscopy. Some effects
      of aperture size, corrector accuracy, and higher order aberrations on probe size
      and image artifacts are calculated. Accumulated small errors in the aberration
      corrector can produce a significant decrease in image contrast, which may be
      important in quantitative image comparisons of theory and experiment. It is
      important to match the objective aperture to the accuracy of the corrector
      instead of just the (third order) spherical aberration of the objective as in the
      commonly used Scherzer conditions.

PMID- 21939616
TI  - Comparing biological effects and potencies of estrone and 17beta-estradiol in
      mature fathead minnows, Pimephales promelas.
AB  - The presence of endocrine active compounds such as estrogens in treated
      wastewater effluent and their effects on aquatic life are causing concern among
      aquatic resource managers. In contrast to 17beta-estradiol (E2), the steroid
      hormone produced by all vertebrates, the biological effects of estrone (E1), one
      of its breakdown products are less understood, even though the aquatic
      concentrations of E1 are often higher than those of E2. The central hypothesis of
      this study was that at environmental concentrations, E1 has estrogenic effects in
      fish, with increased vitellogenin concentrations and decreased reproductive
      success in both male and female fathead minnows, as found with E2. In two
      replicate experiments, we exposed mature fathead minnows to three concentrations
      of each estrogen for 21 days in a flow-through exposure system and measured a
      broad suite of anatomical (body indices, histopathology), physiological (plasma
      vitellogenin), behavioral (nest defense), and reproductive (fecundity, fertility,
      hatching) endpoints. These endpoints have previously been associated with adverse
      effects of estrogenic exposures. While body length and weight parameters were
      unaltered by exposure, secondary sex characteristics exhibited an exposure
      concentrated-related decline in male fathead minnows. Interestingly, low
      concentrations of estrone (~ 15 ng/L) enhanced the aggressiveness of male fathead
      minnows in a behavioral assay. Vitellogenin concentrations in male fish increased
      with higher concentrations of both estrogens, but remained unchanged in all
      female treatments. A decrease in fecundity was observed at high concentrations of
      E2 as compared with control minnows. These results suggest that E1, at
      concentrations previously found in waters receiving wastewater effluent, can have
      reproductive effects on fish.

PMID- 21939618
TI  - Annular electron energy-loss spectroscopy in the scanning transmission electron
      microscope.
AB  - We study atomic-resolution annular electron energy-loss spectroscopy (AEELS) in
      scanning transmission electron microscopy (STEM) imaging with experiments and
      numerical simulations. In this technique the central part of the bright field
      disk is blocked by a beam stop, forming an annular entry aperture to the
      spectrometer. The EELS signal thus arises only from electrons scattered
      inelastically to angles defined by the aperture. It will be shown that this
      method is more robust than conventional EELS imaging to variations in specimen
      thickness and can also provide higher spatial resolution. This raises the
      possibility of lattice resolution imaging of lighter elements or ionization edges
      previously considered unsuitable for EELS imaging.

PMID- 21939619
TI  - Micro-fabricated mechanical sensors for lateral molecular-force microscopy.
AB  - Atomic force microscopy (AFM) has been very successful in measuring forces
      perpendicular to the sample plane. Here, we present the advantages of turning the
      AFM cantilever 90 degrees  in order for it to be perpendicular to the sample.
      This rotation leads naturally to the detection of in-plane forces with some extra
      advantages with respect to the AFM orientation. In particular, the use of
      extremely small (1MUm wide) and soft (k?10(-5)N/m) micro-fabricated cantilevers
      is demonstrated by recording their thermal power spectral density in ambient
      conditions and in liquid. These measurements lead to the complete
      characterisation of the sensors in terms of their stiffness and resonant
      frequency. Future applications, which will benefit from the use of this force
      microscopy technique, are also described.

PMID- 21939615
TI  - Epidemiology of major depression with atypical features: results from the
      National Epidemiologic Survey on Alcohol and Related Conditions (NESARC).
AB  - OBJECTIVE: To examine prevalence, correlates, comorbidity and treatment-seeking
      among individuals with a lifetime major depressive episode (MDE) with and without
      atypical features. METHOD: Data were derived from the 2001-2002 National
      Epidemiologic Survey on Alcohol and Related Conditions, a large cross-sectional
      survey of a representative sample (N = 43,093) of the US population that assessed
      psychiatric disorders using the Alcohol Use Disorder and Associated Disabilities
      Interview Schedule-DSM-IV Version (AUDADIS-IV). Comparison groups were defined
      based on the presence or absence of hypersomnia or hyperphagia in individuals who
      met criteria for lifetime DSM-IV MDE. RESULTS: The presence of atypical features
      during an MDE was associated with greater rates of lifetime psychiatric
      comorbidity, including alcohol abuse, drug dependence, dysthymia, social anxiety
      disorder, specific phobia, and any personality disorder (all P values < .05),
      except antisocial personality disorder, than MDE without atypical features.
      Compared with the latter group, MDE with atypical features was associated with
      female gender, younger age at onset, more MDEs, greater episode severity and
      disability, higher rates of family history of depression, bipolar I disorder,
      suicide attempts, and larger mental health treatment-seeking rates (all P values
      < .05). CONCLUSIONS: Our data provide further evidence for the clinical
      significance and validity of this depressive specifier. Based on the presence of
      any of the 2 reversed vegetative symptoms during an MDE, most of the commonly
      cited validators of atypical depression were confirmed in our study. Major
      depressive episode with atypical features may be more common, severe, and
      impairing than previously documented.

PMID- 21939620
TI  - The role of Poisson's binomial distribution in the analysis of TEM images.
AB  - Frank's observation that a TEM bright-field image acquired under non-stationary
      conditions can be modeled by the time integral of the standard TEM image model
      [J. Frank, Nachweis von objektbewegungen im lichtoptis- chen diffraktogramm von
      elektronenmikroskopischen auf- nahmen, Optik 30 (2) (1969) 171-180.] is re
      derived here using counting statistics based on Poisson's binomial distribution.
      The approach yields a statistical image model that is suitable for image analysis
      and simulation.

PMID- 21939621
TI  - Coherent microscopy by laser optical feedback imaging (LOFI) technique.
AB  - The application of the non-conventional imaging technique LOFI (laser optical
      feedback imaging) to coherent microscopy is presented. This simple and efficient
      technique using frequency-shifted optical feedback needs the sample to be scanned
      in order to obtain an image. The effects on magnitude and phase signals such as
      vignetting and field curvature occasioned by the scanning with galvanometric
      mirrors are discussed. A simple monitoring method based on phase images is
      proposed to find the optimal position of the scanner. Finally, some experimental
      results illustrating this technique are presented.

PMID- 21939622
TI  - Non-monotonic material contrast in scanning ion and scanning electron images.
AB  - 30keV Ga(+) focused ion beam induced secondary electron (iSE) imaging was used to
      determine the relative contrast between several materials. The iSE signal
      compared from C, Si, Al, Ti, Cr, Ni, Cu, Mo, Ag, and W metal layers does not
      decrease with an increase in target atomic number Z(2), and shows a non-monotonic
      relationship between contrast and Z(2). The non-monotonic relationship is
      attributed to periodic fluctuations of the stopping power and sputter yield
      inherent to the ion-solid interactions. In addition, material contrast from
      electron-induced secondary electron (eSE) and backscattered electron (BSE) images
      using scanning electron microscopy (SEM) also shows non-monotonic contrast as a
      function of Z(2), following the periodic behavior of the stopping power for
      electron-solid interactions. A comparison of the iSE and eSE results shows
      similar relative contrast between the metal layers, and not complementary
      contrast as conventionally understood. These similarities in the contrast
      behavior can be attributed to similarities in the periodic and non-monotonic
      function defined by incident particle-solid interaction theory.

PMID- 21939623
TI  - Genetic profiling in inflammatory bowel disease: from association to bedside.

PMID- 21939624
TI  - Trains, tracks, and promotion in an academic medical center.

PMID- 21939625
TI  - Transplanted hepatocytes: wiped out or washed out?

PMID- 21939626
TI  - Randomised study of hypertonic saline infusion during resuscitation from out-of
      hospital cardiac arrest.
AB  - AIM OF THE STUDY: Animal models of hypertonic saline infusion during
      cardiopulmonary resuscitation (CPR) improve survival, as well as myocardial and
      cerebral perfusion during CPR. We studied the effect of hypertonic saline
      infusion during CPR (Guidelines 2000) on survival to hospital admission and
      hospital discharge, and neurological outcome on hospital discharge. METHODS: The
      study was performed by the EMS of Bonn, Germany, with ethical committee approval.
      Study inclusion criteria were non-traumatic out-of-hospital cardiac arrest, aged
      18-80 years, and given of adrenaline (epinephrine) during CPR. Patients were
      randomly infused 2 mlkg(-1) HHS (7.2% NaCl with 6% hydroxyethyl starch
      200,000/0.5 [HES]) or HES over 10 min. RESULTS: 203 patients were randomised
      between May 2001 and June 2004. After HHS infusion, plasma sodium concentration
      increased significantly to 162+/-36 mmoll(-1) at 10 min after infusion and
      decreased to near normal (144+/-6 mmoll(-1)) at hospital admission. Survival to
      hospital admission and hospital discharge was similar in both groups (50/100 HHS
      vs. 49/103 HES for hospital admission, 23/100 HHS vs. 22/103 HES for hospital
      discharge). There was a small improvement in neurological outcome in survivors on
      discharge (cerebral performance category 1 or 2) in the HHS group compared to the
      HES group (13/100 HHS vs. 5/100 HES, p<0.05, odds-ratio 2.9, 95% confidence
      interval 1.004-8.5). CONCLUSION: Hypertonic saline infusion during CPR using
      Guidelines 2000 did not improve survival to hospital admission or hospital
      discharge. There was a small improvement with hypertonic saline in the secondary
      endpoint of neurological outcome on discharge in survivors. Further adequately
      powered studies using current guidelines are needed.

PMID- 21939627
TI  - The role of gap junctions in the arrhythmias of ischemia and infarction.

PMID- 21939628
TI  - Chasing calcium.

PMID- 21939629
TI  - Clinical impact of the number of extrastimuli in programmed electrical
      stimulation in patients with Brugada type 1 electrocardiogram.
AB  - BACKGROUND: Use of programmed electrical stimulation (PES) for risk
      stratification of Brugada syndrome (BrS) is controversial. OBJECTIVE: To
      elucidate the role of the number of extrastimuli during PES in patients with BrS.
      METHODS: Consecutive 108 patients with type 1 electrocardiogram (104 men, mean
      age 46 +/- 12 years; 26 with ventricular fibrillation [VF], 40 with syncope, and
      42 asymptomatic) underwent PES with a maximum of 3 extrastimuli from the right
      ventricular apex and the right ventricular outflow tract. Ventricular arrhythmia
      (VA) was defined as VF or nonsustained polymorphic ventricular tachycardia >15
      beats. Patients with VA induced by a single extrastimulus or double extrastimuli
      were assigned to group SD (Single/Double), by triple extrastimuli to group T
      (Triple), and the remaining patients to group N. RESULTS: VA was induced in 81
      patients (VF in 71 and polymorphic ventricular tachycardia in 10), in 4 by a
      single extrastimulus, in 41 by double extrastimuli, and in 36 by triple
      extrastimuli. During 79 +/- 48 months of follow-up, 24 patients had VF events.
      Although the overall inducibility of VA was not associated with an increased risk
      of VF (log-rank P = .78), group SD had worse prognosis than did group T (P =
      .004). Kaplan-Meier analysis in patients without prior VF also showed that group
      SD had poorer outcome than did group T and group N (P = .001). Positive and
      negative predictive values of VA induction with up to 2 extrastimuli were,
      respectively, 36% and 87%, better than those with up to 3 (23% and 81%,
      respectively). CONCLUSIONS: The number of extrastimuli that induced VA served as
      a prognostic indicator for patients with Brugada type 1 electrocardiogram. Single
      extrastimulus or double extrastimuli were adequate for PES of patients with BrS.

PMID- 21939630
TI  - Vagal activity modulates spontaneous augmentation of J-wave elevation in patients
      with idiopathic ventricular fibrillation.
AB  - BACKGROUND: Although J-wave elevation in the inferolateral leads could be related
      to idiopathic ventricular fibrillation (IVF), little is known about the
      pathophysiologic characteristics of J-wave elevation in patients with IVF.
      OBJECTIVE: This study aimed to determine the relationship between augmentation of
      J-wave elevation and changes in RR interval or autonomic nervous activities in
      patients with IVF. METHODS: Eight patients with IVF and 22 controls with J-wave
      elevation (>=0.1 mV) in lead V5 were studied. The J-wave amplitude was
      automatically measured in lead CM5 of a digital Holter electrocardiogram, and the
      J-RR relationship was determined. Based on the analysis of heart rate
      variability, the relationship between the J-wave amplitude and the natural
      logarithm of high-frequency (HF) components (J-ln HF relationship) or the ratio
      of low frequency (LF) components to HF components (J-LF/HF relationship) was also
      determined. RESULTS: The J-RR slope (mm/s) was greater in patients with IVF than
      in controls (3.5 +/- 0.7 vs 2.4 +/- 0.8; P <.01), as was J-wave amplitude (mm) at
      an RR interval of 1.2 seconds (2.8 +/- 0.9 vs 2.0 +/- 0.6; P <.05). The J-wave
      amplitude was correlated positively with ln HF and negatively with LF/HF, and the
      slopes of both J-ln HF and J-LF/HF regression lines were greater in patients with
      IVF than in controls. During an entire 24-hour period, there was no difference
      between the 2 groups in either HF or LF/HF. Nine of the total 11 episodes (82%)
      of spontaneous ventricular fibrillation occurred between 18:00 and 6:00.
      CONCLUSIONS: In patients with IVF as compared with control subjects, J-wave
      elevation was more strongly augmented during bradycardia and was associated with
      an increase in vagal activity. This could be related to the occurrence of
      ventricular fibrillation predominantly at night in patients with IVF.

PMID- 21939631
TI  - Lutzomyia (Pintomyia) fischeri (Diptera: Psychodidae: Phlebotominae), a probable
      vector of American cutaneous leishmaniasis: detection of natural infection by
      Leishmania (Viannia) DNA in specimens from the municipality of Porto Alegre (RS),
      Brazil, using multiplex PCR assay.
AB  - In order to determine natural Leishmania (Viannia) infection in Lutzomyia
      (Pintomyia) fischeri, a multiplex PCR methodology coupled to non-isotopic
      hybridization was adopted for the analysis of sand fly samples collected by CDC
      light traps in an endemic area of American Cutaneous Leishmaniasis (ACL) in the
      periurban region of the municipality of Porto Alegre, Rio Grande do Sul State,
      Brazil. We analyzed by PCR methodology 560 specimens of Lutzomyia (Pintomyia)
      fischeri (520 females and 40 males). The wild sand flies were grouped into 56
      pools (52 females and 4 males) of 10 each, and positive results were detected in
      2 of the 52 female pools, representing a minimum infection rate of 0.38% based on
      the presence of at least 1 infected insect in the pool. This result associated
      with some local evidence such as anthopophily, spatial distribution in accordance
      with the transmission area and human case incidence, suggests that L.
      (P.)fischeri may be considered as a secondary vector of ACL in the studied
      locality.

PMID- 21939633
TI  - Bacterial transformation using micro-shock waves.
AB  - Shock waves are one of the most competent mechanisms of energy dissipation
      observed in nature. We have developed a novel device to generate controlled micro
      shock waves using an explosive-coated polymer tube. In this study, we harnessed
      these controlled micro-shock waves to develop a unique bacterial transformation
      method. The conditions were optimized for the maximum transformation efficiency
      in Escherichia coli. The maximum transformation efficiency was obtained when we
      used a 30 cm length polymer tube, 100 MUm thick metal foil, 200 mM CaCl(2), 1
      ng/MUl plasmid DNA concentration, and 1*10(9) cell density. The highest
      transformation efficiency achieved (1*10(-5) transformants/cell) was at least 10
      times greater than the previously reported ultrasound-mediated transformation
      (1*10(-6) transformants/cell). This method was also successfully employed for the
      efficient and reproducible transformation of Pseudomonas aeruginosa and
      Salmonella typhimurium. This novel method of transformation was shown to be as
      efficient as electroporation with the added advantage of better recovery of
      cells, reduced cost (40 times cheaper than a commercial electroporator), and
      growth phase independent transformation.

PMID- 21939632
TI  - Proteoglycan 4, a novel immunomodulatory factor, regulates parathyroid hormone
      actions on hematopoietic cells.
AB  - Proteoglycan 4 (PRG4), a critical protective factor in articular joints, is
      implicated in hematopoietic progenitor cell expansion and megakaryopoiesis. PRG4
      loss-of-function mutations result in camptodactyly-arthropathy-coxa vara
      pericarditis (CACP) syndrome, which is characterized primarily by precocious
      joint failure. PRG4 was identified as a novel parathyroid hormone (PTH)
      responsiveness gene in osteoblastic cells in bone, and was investigated as a
      potential mediator of PTH actions on hematopoiesis. Sixteen-week-old Prg4(-/-)
      mutant and Prg4(+/+) wild-type mice were treated daily with intermittent PTH
      (residues 1-34) or vehicle for 6 weeks. At 22 weeks of age, Prg4 mutant mice had
      increased peripheral blood neutrophils and decreased marrow B220(+) (B
      lymphocytic) cells, which were normalized by PTH. The PTH-induced increase in
      marrow Lin(-)Sca-1(+)c-Kit(+) (hematopoietic progenitor) cells was blunted in
      mutant mice. Basal and PTH-stimulated stromal cell-derived factor-1 (SDF-1) was
      decreased in mutant mice, suggesting SDF-1 as a candidate regulator of
      proteoglycan 4 actions on hematopoiesis in vivo. PTH stimulation of IL-6 mRNA was
      greater in mutant than in wild-type calvaria and bone marrow, suggesting a
      compensatory mechanism in the PTH-induced increase in marrow hematopoietic
      progenitor cells. In summary, proteoglycan 4 is a novel PTH-responsive factor
      regulating immune cells and PTH actions on marrow hematopoietic progenitor cells.

PMID- 21939634
TI  - Cytochrome c oxidase and nitric oxide in action: molecular mechanisms and
      pathophysiological implications.
AB  - BACKGROUND: The reactions between Complex IV (cytochrome c oxidase, CcOX) and
      nitric oxide (NO) were described in the early 60's. The perception, however, that
      NO could be responsible for physiological or pathological effects, including
      those on mitochondria, lags behind the 80's, when the identity of the endothelial
      derived relaxing factor (EDRF) and NO synthesis by the NO synthases were
      discovered. NO controls mitochondrial respiration, and cytotoxic as well as
      cytoprotective effects have been described. The depression of OXPHOS ATP
      synthesis has been observed, attributed to the inhibition of mitochondrial
      Complex I and IV particularly, found responsible of major effects. SCOPE OF
      REVIEW: The review is focused on CcOX and NO with some hints about
      pathophysiological implications. The reactions of interest are reviewed, with
      special attention to the molecular mechanisms underlying the effects of NO
      observed on cytochrome c oxidase, particularly during turnover with oxygen and
      reductants. MAJOR CONCLUSIONS AND GENERAL SIGNIFICANCE: The NO inhibition of CcOX
      is rapid and reversible and may occur in competition with oxygen. Inhibition
      takes place following two pathways leading to formation of either a relatively
      stable nitrosyl-derivative (CcOX-NO) of the enzyme reduced, or a more labile
      nitrite-derivative (CcOX-NO(2)(-)) of the enzyme oxidized, and during turnover.
      The pathway that prevails depends on the turnover conditions and concentration of
      NO and physiological substrates, cytochrome c and O(2). All evidence suggests
      that these parameters are crucial in determining the CcOX vs NO reaction pathway
      prevailing in vivo, with interesting physiological and pathological consequences
      for cells.

PMID- 21939635
TI  - Design of photoactive ruthenium complexes to study electron transfer and proton
      pumping in cytochrome oxidase.
AB  - This review describes the development and application of photoactive ruthenium
      complexes to study electron transfer and proton pumping reactions in cytochrome c
      oxidase (CcO). CcO uses four electrons from Cc to reduce O(2) to two waters, and
      pumps four protons across the membrane. The electron transfer reactions in
      cytochrome oxidase are very rapid, and cannot be resolved by stopped-flow mixing
      techniques. Methods have been developed to covalently attach a photoactive
      tris(bipyridine)ruthenium group [Ru(II)] to Cc to form Ru-39-Cc. Photoexcitation
      of Ru(II) to the excited state Ru(II*), a strong reductant, leads to rapid
      electron transfer to the ferric heme group in Cc, followed by electron transfer
      to Cu(A) in CcO with a rate constant of 60,000s(-1). Ruthenium kinetics and
      mutagenesis studies have been used to define the domain for the interaction
      between Cc and CcO. New ruthenium dimers have also been developed to rapidly
      inject electrons into Cu(A) of CcO with yields as high as 60%, allowing
      measurement of the kinetics of electron transfer and proton release at each step
      in the oxygen reduction mechanism.

PMID- 21939636
TI  - Low temperature FTIR spectroscopy provides new insights in the pH-dependent
      proton pathway of proteorhodopsin.
AB  - In the presented study the low pH photocycle of proteorhodopsin is extensively
      investigated by means of low temperature FTIR spectroscopy. Besides the already
      well-known characteristics of the all-trans and 13-cis retinal vibrations the 77K
      difference spectrum at pH 5.1 shows an additional negative signal at 1744 cm(-1)
      which is interpreted as indicator for the L state. The subsequent photocycle
      steps are investigated at temperatures higher than 200K. The combination of
      visible and FTIR spectroscopy enabled us to observe that the deprotonation of the
      Schiff base is linked to the protonation of an Asp or Glu side chain - the new
      proton acceptor under acidic conditions. The difference spectra of the late
      intermediates are characterized by large amide I changes and two further bands ((
      )1751 cm(-1)/(+)1725 cm(-1)) in the spectral region of the Asp/Glu nu(C=O)
      vibrations. The band position of the negative signature points to a transient
      deprotonation of Asp-97. In addition, the pH dependence of the acidic photocycle
      was investigated. The difference spectra at pH 5.5 show distinct differences
      connected to changes in the protonation state of key residues. Based on our data
      we propose a three-state model that explains the complex pH dependence of PR.

PMID- 21939637
TI  - VEGF, Bcl-2 and Bad regulated by angiopoietin-1 in oleic acid induced acute lung
      injury.
AB  - Molecular mechanisms of acute lung injury (ALI) are poorly defined. Our previous
      study demonstrated that recombinant angiopoietin-1 (Ang1) can protect against
      oleic acid (OA) induced ALI at an early stage. The purpose of this study was to
      elucidate whether vascular endothelial growth factor (VEGF), Bcl-2, and Bad,
      phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) play any role in the
      protective mechanism of recombinant Ang1 in OA-induced ALI. All BALB/C mice were
      administered a single dose of OA to induce lung injury. Lungs, bronchoalveolar
      lavage fluid (BALF), and serum were harvested at certain time points. The
      expression of VEGF, Bcl-2, Bad, PI3K/Akt, and the histological changes in the
      lung, and the levels of VEGF, IL-6, and IL-10 in serum and BALF were examined. A
      second cohort of mice was followed for survival for 7 days. We observed increased
      expression of VEGF in BALF and serum and reduced expression of VEGF in lung
      tissue. Recombinant Ang1 treatment, however, up-regulated VEGF expression and p
      Akt/Akt in lung tissue but down-regulated VEGF expression in BALF and serum. OA
      led to a decrease of anti-apoptotic marker Bcl-2 and a marked increase of pro
      apoptotic marker Bad. Compared with the ALI group, in the recombinant Ang1
      treated group, Bcl-2 expression was restored, and Bad expression was clearly
      attenuated. In addition, recombinant Ang1 attenuated the lung pathological
      changes and improved the survival of mice. These findings suggest that
      recombinant Ang1 may be a promising potential treatment for ALI. It seems that
      VEGF is mediated by PI3K/Akt pathway which is required for Ang1-mediated
      protection of lung injury. Activation of Akt stimulates expression of Bcl-2 and
      inhibits the expression of Bad, thus inhibiting the execution of apoptosis.

PMID- 21939638
TI  - Increased susceptibility to Candida infection following cecal ligation and
      puncture.
AB  - Secondary infection following septic insult represents a significant cause of
      morbidity and mortality in hospitalized patients. Sepsis induced
      immunosuppression is a major factor in the host's susceptibility to nosocomial
      infections and Candida albicans accounts for a growing number of these. Given the
      importance of improving our understanding of the immune response to sepsis and
      the increasing rates of C. albicans infections, we sought to develop a murine
      model of double injury consisting of primary peritonitis, i.e., cecal ligation
      and puncture (CLP), followed by a secondary challenge of C. albicans. As observed
      in previous work, after primary injury the immune profile of the host changes
      over time. Therefore, while keeping the mortality rates from the respective
      individual injuries low, we altered the timing of the secondary injury between
      two post-CLP time points, day two and day four. Mice subjected to C. albicans
      infection following CLP have significantly different survival rates dependent
      upon timing of secondary injury. Animals challenged with C. albicans at two days
      post CLP had 91% mortality whereas animals challenged at four days had 47%
      mortality. This improvement in survival at four days was associated with
      restoration of innate cell populations and as evidenced by stimulated
      splenocytes, increases in certain inflammatory cytokines. In addition, we show
      that susceptibility to C. albicans infection following CLP is dependent upon the
      depth of immunosuppression. Although at four days post-CLP there is a partial
      reconstitution of the immune system, these animals remain more susceptible to
      infection compared to their single injury (C. albicans alone) counterparts.
      Collectively, these studies demonstrate that immunosuppression following initial
      septic insult changes over time. This novel, two hit model of CLP followed by
      Candida provides additional insight into the immune compromised state created by
      primary peritonitis, and thereby opens up another avenue of investigation into
      the causes and possible cures of an emerging clinical problem.

PMID- 21939639
TI  - Identification of the endogenous cysteine-rich peptide trissin, a ligand for an
      orphan G protein-coupled receptor in Drosophila.
AB  - There are many orphan G protein-coupled receptors (GPCRs), for which ligands have
      not yet been identified, in both vertebrates and invertebrates, such as
      Drosophila melanogaster. Identification of their cognate ligands is critical for
      understanding the function and regulation of such GPCRs. Indeed, the discovery of
      bioactive peptides that bind GPCRs has enhanced our understanding of mechanisms
      underlying many physiological processes. Here, we identified an endogenous ligand
      of the Drosophila orphan GPCR, CG34381. The purified ligand is a peptide
      comprised of 28 amino acids with three intrachain disulfide bonds. The preprotein
      is coded for by gene CG14871. We designated the cysteine-rich peptide "trissin"
      (it means for triple S-S bonds) and characterized the structure of intrachain
      disulfide bonds formation in a synthetic trissin peptide. Because the expression
      of trissin and its receptor is reported to predominantly localize to the brain
      and thoracicoabdominal ganglion, trissin is expected to behave as a neuropeptide.
      The discovery of trissin provides an important lead to aid our understanding of
      cysteine-rich peptides and their functional interaction with GPCRs.

PMID- 21939640
TI  - IL-17F deficiency inhibits small intestinal tumorigenesis in ApcMin/+ mice.
AB  - IL-17 plays an important role in gut homeostasis. However, the role of IL-17F in
      intestinal tumorigenesis has not been addressed. Here we demonstrate that
      ablation of IL-17F significantly inhibits spontaneous intestinal tumorigenesis in
      the small intestine of Apc(Min/+) mice. IL-17F ablation decreased IL-1beta and
      Cox-2 expression as well as IL-17 receptor C (IL-17RC) expression, which were
      increased in tumors from Apc(Min/+) mice. Lack of IL-17F did not reverse the
      splenomegaly but partially restored thymic atrophy, suggesting a local effect of
      IL-17F in the intestine. IL-17F deficient Apc(Min/+) mice showed a significant
      decrease in immune cell infiltration in the lamina propria. Interestingly, the
      expression of IL-17A from CD4 T cells in the lamina propria remains unchanged in
      the absence of IL-17F. Collectively, our results suggest the proinflammatory and
      essential role of IL-17F to develop spontaneous intestinal tumorigenesis in
      Apc(Min/+) mice in the presence of IL-17A.

PMID- 21939641
TI  - Impact of genetic polymorphisms of cytochrome P450 2 C (CYP2C) enzymes on the
      drug metabolism and design of antidiabetics.
AB  - CYP2C enzymes are responsible for the oxidative metabolism of a diverse number of
      drugs for the treatment of type 2 diabetes mellitus, a severe metabolic disorder
      with high prevalence. Various clinical studies found the close association
      between CYP2C polymorphisms and altered pharmacokinetics, toxicological profiles,
      and drug-drug interactions of antidiabetic drugs. In this brief review, we
      discussed the impact of CYP2C polymorphisms on the metabolic fate of small
      molecule antidiabetics including sulfonylureas, meglitinides, thiazolidinediones,
      gliptins, and gliflozins, with the key drug-protein molecular interactions
      highlighted.

PMID- 21939642
TI  - Using fluorescence to locate intercalants within the lipid bilayer of liposomes,
      bioliposomes and erythrocyte ghosts.
AB  - In previous work, we have shown the utility of the "NMR technique" in locating
      intercalants within the lipid bilayer. We describe herein the development of a
      more sensitive and complementary "fluorescence technique" for this purpose and
      its application to liposomes, bioliposomes and erythrocyte ghosts. This technique
      is based on the observation in selected compounds of an excellent correlation
      between the emission wavelength (lambda(em)) and Dimroth-Reichardt E(T)(30)
      polarity parameter for the solvent in which the fluorescence emission spectrum
      was obtained.

PMID- 21939643
TI  - Development of a point of care testing tool to classify peritoneal effusion as
      exudate and transudate.
AB  - BACKGROUND: Recently we developed a bedside test to classify pleural effusion
      into exudate and transudate but point of care classification of peritoneal
      effusion is yet not published. METHODS: We analyzed the Boyer's criteria
      parameters from bloodless peritoneal fluid and classified the biofluid as exudate
      or transudate and also estimated some parameters of oxidative stress in the
      biofluid by established spectrophotometric procedure. Two hundred microliters of
      sample was used and 10 MUl of 30% hydrogen peroxide was added, followed by
      inspection of the sample for the appearance of bubbles. RESULTS: All exudative
      ascitic fluids (n=50) have shown the appearance of profuse bubbles within 1 min
      addition of hydrogen peroxide along with significantly more catalase activity
      compared to transudate. All transudative ascitic fluids (n=50) have not shown
      bubble formation within 1 min after the addition of hydrogen peroxide. The
      exudate does not show bubble formation if added with catalase inhibitors prior to
      the addition of hydrogen peroxide. Blood mixed transudate have shown profuse
      bubble formation after the addition of hydrogen peroxide. CONCLUSION: The
      hydrogen peroxide bubbling reaction has the potential to be developed as a point
      of care test to classify peritoneal fluid as exudate or transudate.

PMID- 21939644
TI  - Evaluation of automated serum des-gamma-carboxyprothrombin (DCP) assays for
      detecting hepatocellular carcinoma.
AB  - OBJECTIVES: We evaluated two new autoanalyzers, MUTAS and Lumipulse for des-gamma
      carboxyprothrombin (DCP) assay. MATERIAL AND METHODS: Analytical performance was
      evaluated, and the upper reference limit of the 97.5th percentile for DCP was re
      established using sera from 140 healthy individuals. DCP levels were determined
      by the two autoanalyzers and EIA in a total of 239 sera from HCC patients (n=120)
      and those without HCC (n=119). RESULTS: Total imprecision of the two automated
      assays was <5% CV. Analytical measurement ranges (AMRs) were verified to be
      linear. The new reference limits were 29.5 mAU/mL for MUTAS and 35.0 mAU/mL for
      Lumipulse. There were proportional and constant biases between the results from
      the autoanalyzers and those from EIA. CONCLUSION: The two newly developed DCP
      assays showed high analytical performance, but re-establishment of reference
      limits would be necessary. The new analyzers could be useful for clinical
      laboratories because of convenience of operation and wide AMRs.

PMID- 21939645
TI  - Lack of association of serum resistin levels with metabolic syndrome criteria in
      obese female patients.
AB  - BACKGROUND: As unclear data of resistin relation with metabolic syndrome has been
      published, we decide to investigate the association between metabolic syndrome
      and resistin levels in female obese subjects. SUBJECTS: A sample of 551 female
      obese subjects was analyzed. A complete nutritional and biochemical evaluation
      was performed. RESULTS: Levels of C reactive protein, weight, fat mass and waist
      circumference were higher in patients in the highest tertile group of resistin
      than the lowest and middle tertiles of resistin. In the multivariate analysis
      with metabolic syndrome presence/absence-, only fat mass remained as an
      independent predictor in the model. Resistin concentration increases 0.020 ng/ml
      (CI95%:0.006-0.038) for each kg of fat mass in female obese subjects. CONCLUSION:
      Only fat mass was associated in an independent way. Serum resistin was not
      associated with the accumulation of MetS factors or the diagnosis of MetS in
      obese female subjects.

PMID- 21939646
TI  - Seasonal variation and stability of matrix metalloproteinase-9 activity and
      tissue inhibitor of matrix metalloproteinase-1 with storage at -80 degrees C.
AB  - OBJECTIVE: To determine whether active matrix metalloproteinase (MMP)-9 and
      tissue inhibitor of matrix metalloproteinase (TIMP)-1 displayed seasonal
      variation and were stable in storage. METHODS: Plasma active MMP-9 and TIMP-1
      were measured at three time-points in 163 individuals. RESULT: There was no
      evidence for seasonal variation or declining levels for up to three years of
      storage at -80 degrees C. CONCLUSION: Active MMP-9 and TIMP-1 appear to be stable
      seasonally, and in storage for at least three years.

PMID- 21939647
TI  - Detection of mammaglogin A in blood from breast cancer patients, before and after
      treatment, using a one-tube nested PCR protocol. Association with the absence of
      tumor estrogen receptors.
AB  - OBJECTIVE: A one-tube nested RT-PCR protocol was set up and used to detect
      mammaglobin A (MGA) expression in blood samples from breast cancer patients. The
      correlation of MGA detection with prognostic factors was analyzed. DESIGN AND
      METHODS: Total RNA from nucleated blood cells was extracted from 65 breast cancer
      patients (before surgery and after the treatments) and 18 healthy subjects and
      used to detect MGA expression by a modified nested RT-PCR. RESULTS: MGA
      expression was detected in 38.4% of patients before surgery, and in 50% and 36.8%
      of post-treatment samples from patients that expressed MGA or were MGA negative
      before surgery, respectively. MGA detection was associated with the absence of
      tumor estrogen receptors (p=0.004). CONCLUSIONS: MGA detection by the modified
      nested RT-PCR is a specific marker for circulating tumor cells in patients with
      breast carcinoma and a negative prognostic factor for the disease.

PMID- 21939648
TI  - Novel serum biomarkers in carotid artery stenosis: useful to identify the
      vulnerable plaque?
AB  - OBJECTIVES: Serum biomarkers representing inflammatory activity in vulnerable
      carotid plaques may be used to identify high-risk patients for cerebral ischemic
      events. We aimed to analyze the relationship between concentrations of four novel
      biomarkers and neurological symptoms: Neopterin, PTX3, sCD163, and sTREM-1. In
      addition, we analyzed the relationship between these markers and the presence of
      coronary (CAD) and peripheral (PAD) artery disease. DESIGN AND METHODS: Serum
      biomarker levels were determined in 100 patients undergoing carotid
      endarterectomy; 33 for stroke, 32 for transient ischemic attack, and 23 for
      amaurosis fugax. 12 Patients were asymptomatic. Risk factors for atherosclerotic
      disease and history of CAD and PAD were also assessed. RESULTS: Symptomatic
      patients did not show significantly elevated biomarker levels compared to
      asymptomatic patients and levels did not differ among symptomatic subgroups.
      Neopterin levels were elevated in patients with concomitant coronary and
      peripheral artery disease (CAD (32%) 10.2 +/- 6.6 vs no CAD (68%) 7.6 +/- 2.9
      nmol/L, PAD (20%) 12.3 +/- 7.4 vs no PAD (80%) 7.5 +/- 3.0 nmol/L, p<0.05). sTREM
      1 was elevated in patients with CAD (50.8 +/- 53.2 vs 28.0 +/- 31.6 ng/L,
      p<0.05). PTX3 and sCD163 were not significantly elevated in CAD nor PAD.
      CONCLUSION: Our findings suggest that serum neopterin and sTREM-1 levels may be
      related to the presence of atherosclerotic disease, but not to carotid plaque
      vulnerability.

PMID- 21939649
TI  - Combined use of high-sensitivity C-reactive protein and apolipoprotein
      B/apolipoprotein A-1 ratio prior to elective coronary angiography and oral
      glucose tolerance tests.
AB  - OBJECTIVES: The study aimed to investigate the predictive value of the
      combination of high-sensitivity C-reactive protein (hs-CRP) and apolipoprotein B
      (apoB)/apoA-1 ratio for the outcomes of coronary angiography (CAG),
      echocardiography and oral glucose tolerance tests (OGTTs). DESIGN AND METHODS: Hs
      CRP, apoB, apoA-1, and the profiles of CAG, echocardiography and OGTTs as well as
      traditional risk factors were measured in 1757 cardiology patients. RESULTS: Hs
      CRP or apoB/apoA-1 ratio was significantly correlated with the presence and
      severity of angiographic profiles, the levels of left ventricular (LV) ejection
      fraction, LV mass and LV mass index, and the presence of abnormal glucose
      metabolism. The combination of hs-CRP and apoB/apoA-1 ratio had greater
      correlation with abnormal glucose metabolism than its individual components in
      patients with normal fasting glucose, and was an independent predictor for
      coronary artery disease. CONCLUSIONS: The combination of hs-CRP and apoB/apoA-1
      ratio may be a strong predictor for coronary artery disease and abnormal glucose
      metabolism.

PMID- 21939650
TI  - Plasma visfatin and retinol binding protein-4 levels in patients with type 2
      diabetes mellitus and their relationship to adiposity and fatty liver.
AB  - OBJECTIVES: We investigated whether plasma visfatin and binding protein-4 (RBP-4)
      levels correlate with obesity and type 2 diabetes mellitus (T2DM). DESIGN AND
      METHODS: Two groups were enrolled: Group 1: 40 patients with T2DM and Group 2: 40
      age- and gender-matched healthy controls. Both groups were subdivided according
      to body mass index (BMI) into non-obese (BMI < 25 kg/m(2)) and obese subjects
      (BMI >= 30 kg/m(2)) (20 each). RESULTS: Plasma visfatin and RBP-4 levels were
      significantly increased in T2DM patients compared with controls with similar BMI
      values (for both p<0.001). Plasma visfatin and RBP-4 concentrations correlated
      with BMI, waist/hip ratio, insulin and homeostatic model assessment insulin
      resistance (HOMA(IR)). Visfatin and RBP-4 correlated with visceral fat and liver
      fat in diabetic patients (for both p<0.001). CONCLUSION: Visfatin level was
      increased in T2DM, possibly related to hyperglycemia. Plasma RBP-4 correlated
      positively with liver fat and HOMA(IR) which may reflect its effects on hepatic
      insulin sensitivity.

PMID- 21939651
TI  - Autism spectrum disorder: When biochemical and genetic profiles don't match - is
      sample size and selection bias the culprit?

PMID- 21939652
TI  - Autophagy is induced by 3beta-O-succinyl-lupeol (LD9-4) in A549 cells via up
      regulation of Beclin 1 and down-regulation mTOR pathway.
AB  - The purpose of this study is to investigate the antitumor activity of a new
      derivative of lupeol-3beta-O-succinyl-lupeol (LD9-4) and the molecular mechanism
      underlying cell death in human non-small cell lung cancer A549 cells. The results
      revealed that LD9-4 inhibited A549 cell proliferation in a time- and dose
      dependent manner, with an IC(50) value of 5.78 +/- 0.48 MUM after cells exposed
      to LD9-4 for 72 h. Markers indicative of apoptosis (cell cycle arrest,
      phosphatidylserine externalization and Hoechst33258 staining) were uniformly
      negative in LD9-4 exposed cells. Interestingly, transmission electron microscope,
      MDC staining and LC3 level determination all confirmed that autophagy was induced
      in LD9-4 treated A549 cells. Furthermore, we found that LD9-4-induced autophagy
      in A549 cells was associated with the increase of intracellular reactive oxygen
      species and the decrease of phosphorylated mTOR and p70S6K levels. In the
      meanwhile, both mRNA and protein levels of Beclin 1 were up-regulated in a time
      dependent manner. Our data suggest that autophagy is induced by LD9-4 in A549
      cells, and the accumulating reactive oxygen species, up-regulation of Beclin 1
      and inhibition of the mTOR signaling pathway are involved in this process.

PMID- 21939653
TI  - Karanjin from Pongamia pinnata induces GLUT4 translocation in skeletal muscle
      cells in a phosphatidylinositol-3-kinase-independent manner.
AB  - Insulin-stimulated glucose uptake in skeletal muscle is decreased in type 2
      diabetes due to impaired translocation of insulin-sensitive glucose transporter 4
      (GLUT4) from intracellular pool to plasma membrane. Augmenting glucose uptake
      into this tissue may help in management of type 2 diabetes. Here, the effects of
      an identified antihyperglycemic molecule, karanjin, isolated from the fruits of
      Pongamia pinnata were investigated on glucose uptake and GLUT4 translocation in
      skeletal muscle cells. Treatment of L6-GLUT4myc myotubes with karanjin caused a
      substantial increase in the glucose uptake and GLUT4 translocation to the cell
      surface, in a concentration-dependent fashion, without changing the total amount
      of GLUT4 protein and GLUT4 mRNA. This effect was associated with increased
      activity of AMP-activated protein kinase (AMPK). Cycloheximide treatment
      inhibited the effect of karanjin on GLUT4 translocation suggesting the
      requirement of de novo synthesis of protein. Karanjin-induced GLUT4 translocation
      was further enhanced with insulin and the effect is completely protected in the
      presence of wortmannin. Moreover, karanjin did not affect the phosphorylation of
      AKT (Ser-473) and did not alter the expression of the key molecules of insulin
      signaling cascade. We conclude that karanjin-induced increase in glucose uptake
      in L6 myotubes is the result of an increased translocation of GLUT4 to plasma
      membrane associated with activation of AMPK pathway, in a PI-3-K/AKT-independent
      manner.

PMID- 21939654
TI  - U bodies respond to nutrient stress in Drosophila.
AB  - The neurodegenerative disease spinal muscular atrophy (SMA) is caused by mutation
      of the survival motor neuron 1 (SMN1) gene. Cytoplasmic SMN protein-containing
      granules, known as U snRNP bodies (U bodies), are thought to be responsible for
      the assembly and storage of small nuclear ribonucleoproteins (snRNPs) which are
      essential for pre-mRNA splicing. U bodies exhibit close association with
      cytoplasmic processing bodies (P bodies), which are involved in mRNA decay and
      translational repression. The close association of the U body and P body in
      Drosophila resemble that of the stress granule and P body in yeast and mammalian
      cells. However, it is unknown whether the U body is responsive to any stress.
      Using Drosophila oogenesis as a model, here we show that U bodies increase in
      size following nutritional deprivation. Despite nutritional stress, U bodies
      maintain their close association with P bodies. Our results show that U bodies
      are responsive to nutrition changes, presumably through the U body-P body
      pathway.

PMID- 21939655
TI  - Cellular repressor of E1A-stimulated genes regulates vascular endothelial cell
      migration by the ILK/AKT/mTOR/VEGF(165) signaling pathway.
AB  - The migration of vascular endothelial cells plays a critical role in a variety of
      vascular physiological and pathological processes, such as embryonic development,
      angiogenesis, wound healing, re-endothelialization, and vascular remodeling. This
      study clarified the role and mechanism of a new vascular homeostasis regulator,
      Cellular repressor of E1A-stimulated genes (CREG), in the migration of primary
      human umbilical vein endothelial cells (HUVECs). A wound healing assay and
      transwell migration model showed that upregulation of CREG expression induced
      HUVEC migration and it was positively correlated with the expression of vascular
      endothelial growth factor. Furthermore, wild type integrin-linked kinase reversed
      the poor mobility of CREG knock-down HUVECs; in contrast, kinase-dead integrin
      linked kinase weakened the migration of HUVECs. We also studied the effect of
      CREG on HUVEC migration by the addition of an mTOR inhibitor, recombinant
      vascular endothelial growth factor(165), neutralizing antibody of vascular
      endothelial growth factor(165) and AKT siRNA, and we concluded that CREG induces
      endothelial cell migration by activating the integrin-linked
      kinase/AKT/mTOR/VEGF(165) signaling pathway.

PMID- 21939656
TI  - NUMB does not impair growth and differentiation status of experimental gliomas.
AB  - The cell fate determinant NUMB orchestrates asymmetric cell division in flies and
      mammals and has lately been suggested to have a tumor suppressor function in
      breast and lung cancer. Here, we studied NUMB in the context of malignant
      gliomas. We used ectopic expression of NUMB in order to inhibit proliferation and
      induce differentiation in glioma cells by alteration of Notch, Hedgehog and p53
      signaling. We found that NUMB is consistently expressed in glioma biopsies with
      predominance of NUMB2/4 isoforms as determined by isoform-specific real-time PCR
      and Western blotting. Upon lentiviral overexpression, in vitro proliferation rate
      and the grade of differentiation as assessed by morphology and expression of
      neural and glial markers remained unchanged. Orthotopic xenografts of NUMB
      transduced human U87 glioma cells could be established in nude rats without
      impairing engraftment or causing significant changes in morphology based on
      magnetic resonance imaging (MRI). The previously reported alteration of Hedgehog
      and p53 signaling by NUMB could not be recapitulated in glioma cells. We thus
      show that in experimental gliomas, NUMB overexpression most likely does not exert
      a tumor suppressor function such as seen in epithelial cancers.

PMID- 21939657
TI  - Ketogenic diet-induced peroxisome proliferator-activated receptor-gamma
      activation decreases neuroinflammation in the mouse hippocampus after kainic acid
      induced seizures.
AB  - Similar to fasting, the ketogenic diet (KD) has anti-inflammatory effects and
      protects against excitotoxicity-mediated neuronal cell death. Recent studies have
      shown that peroxisome proliferator-activated receptor (PPAR)gamma has anti
      inflammatory effects in seizure animal models. However, the exact mechanisms
      underlying the anti-inflammatory effects of the KD have not been determined for
      seizures. Here we investigated the effect of the KD and acetoacetate (AA) on
      neuroinflammation in a seizure animal model and glutamate-treated HT22 cells,
      respectively. Mice were fed the KD for 4 weeks and sacrificed 2 or 6h after KA
      injection. The KD reduced hippocampal tumor necrosis factor alpha (TNF-alpha)
      levels and nuclear factor (NF)-kappaB translocation into the nucleus 2h after KA
      treatment. KD-induced PPARgamma activation was decreased by KA in neurons as
      assessed by western blotting and immunofluorescence. Finally, the KD inhibited
      cyclooxygenase (COX)-2 and microsomal prostaglandin E(2) synthase-1 (mPGES-1)
      expression in the hippocampus 6h after KA treatment. AA treatment also protected
      against glutamate-induced cell death in HT22 cells by reducing TNF-alpha and
      PPARgamma-mediated COX-2 expression. Thus, the KD may inhibit neuroinflammation
      by suppressing a COX-2-dependent pathway via activation of PPARgamma by the KD or
      AA.

PMID- 21939658
TI  - Evaluation of thiosemicarbazones and semicarbazones as potential agents anti
      Trypanosoma cruzi.
AB  - Synthetic thiosemicarbazones and semicarbazones were evaluated for their
      Trypanosoma cruzi trypomastigotes obtained from LLC-MK2 cell cultures. In
      general, thiosemicarbazone derivatives were most effective and among them the 4-N
      (2'-methoxy styryl)-thiosemicarbazone was chosen, to compare the in vitro effect
      against amastigotes of T. cruzi lodged in mouse peritoneal and human macrophages.
      A potent trypanocidal effect was observed that was more pronounced against
      parasites internalized in human macrophages. A potential target for this compound
      was also evaluated by measuring the nitric oxide synthase activity through NADPH
      consumption. A significant decrease in enzyme activity was observed. In contrast
      to the cytotoxic effect observed with benznidazole, no macrophage toxicity was
      observed for any of the compounds, indicating that their activity was specific
      for the parasite forms investigated.

PMID- 21939659
TI  - Essential role of the metal-ion in the IPM-assisted domain closure of 3
      isopropylmalate dehydrogenase.
AB  - X-ray structures of 3-isopropylmalate dehydrogenase (IPMDH) do not provide
      sufficient information on the role of the metal-ion in the metal-IPM assisted
      domain closure. Here solution studies were carried out to test its importance.
      Small-angle X-ray scattering (SAXS) experiments with the Thermus thermophilus
      enzyme (complexes with single substrates) have revealed only a very marginal (0
      5%) extent of domain closure in the absence of the metal-ion. Only the metal-IPM
      complex, but neither the metal-ion nor the free IPM itself, is efficient in
      stabilizing the native protein conformation as confirmed by denaturation
      experiments with Escherichia coli IPMDH and by studies of the characteristic
      fluorescence resonance energy transfer (FRET) signal (from Trp to bound NADH)
      with both IPMDHs. A possible atomic level explanation of the metal-effect is
      given.

PMID- 21939660
TI  - Acute effects of corticosterone injection on paternal behavior in California
      mouse (Peromyscus californicus) fathers.
AB  - Glucocorticoids are thought to mediate the disruption of parental behavior in
      response to acute and chronic stress. Previous research supports their role in
      chronic stress; however, no study has experimentally tested the effects of acute
      glucocorticoid elevation on paternal behavior. We tested the prediction that
      acute corticosterone (CORT) increases would decrease paternal behavior in
      California mouse fathers and would lead to longer-term effects on reproductive
      success, as even short-term increases in CORT have been shown to produce lasting
      effects on the hypothalamic-pituitary-adrenal axis. First-time fathers were
      injected with 30 mg/kg CORT, 60 mg/kg CORT or vehicle, or left unmanipulated.
      Interactions between the male and its pup(s) were recorded 1.5-2h after injection
      and scored for paternal and non-paternal behavior. Treatment groups were combined
      into control (unmanipulated + vehicle, n = 15) and CORT (30 mg/kg + 60 mg/kg, n =
      16) for analysis based on resulting plasma CORT concentrations. CORT treatment
      did not alter paternal or non-paternal behaviors or any long-term measures (male
      body mass or temperature, pup growth rate, pup survival, interbirth interval,
      number or mass of pups born in the second litter). Fathers showed a significant
      rise in body mass at day 30 postpartum, followed by a decrease in body mass after
      the birth of the second litter; however, this pattern did not differ between the
      CORT and control groups. In summary, acute elevation of plasma CORT did not alter
      direct paternal behavior, body mass, or reproductive outcomes, suggesting that
      acute CORT elevation alone does not overtly disrupt paternal care in this
      biparental mammal.

PMID- 21939661
TI  - Robust recombinant FcRn production in mammalian cells enabling oriented
      immobilization for IgG binding studies.
AB  - The MHC class-I related receptor or neonatal Fc receptor (FcRn) protects IgG and
      albumin from degradation by rescuing them in endothelial cells in a pH dependent
      fashion and consequently increases their respective half-lives. Monoclonal
      antibody-based therapies are of increasing interest and characterizing the
      interaction with FcRn is important for the development of an antibody candidate.
      In order to facilitate the production of soluble FcRn suitable for interaction
      studies, we generated semi-stable pools co-expressing FcRn alpha-chain, beta2
      microglobulin, biotin ligase and EGFP using a dual promoter, multi-cistronic
      vector. Human and mouse FcRn were purified in the mg/L range of culture medium
      and a single purification step was sufficient to reach a high level of purity.
      The receptors were characterized by ELISA, flow cytometry and surface plasmon
      resonance and shown to be functional. The single site biotinylation facilitated
      the directional immobilization of FcRn on the sensor chip and significantly
      increased the response level of the surface compared to amine coupling used in
      previous studies. Using this system, the affinity constants of seven IgGs, from
      various species and isotypes, were determined for human and mouse FcRn, including
      two hamster isotypes. These results confirm the higher selectivity of the human
      receptor and the promiscuous binding of mFcRn to IgGs from different species.

PMID- 21939662
TI  - Effect of acclimation on heat-escape temperatures of two aphid species:
      Implications for estimating behavioral response of insects to climate warming.
AB  - An aphid usually stays at one feeding site for a long time to achieve its
      development and reproduction, while high temperatures can make it decide to
      escape from heat stress. Climate warming increases daily high-temperature both in
      degree and time. However, it remains unknown whether such heat-escape behavior
      will be influenced by those daily temperature changes. In this study, a wheat
      leaf temperature gradient was created based on field microhabitat temperatures.
      We defined a parameter, heat-escape temperature (HET) to describe the critical
      temperature at which an aphid turns back when it walks along the gradient from
      mild temperature to high temperatures. HET indicates behavioral responses of the
      aphids to heat stress. Two aphid species, Sitobion avenae and Rhopalosiphum padi,
      main economic pests in temperate areas were selected as test insects. Detailed
      studies were conducted on the temperature gradient to reveal effects of
      acclimation temperature, time, and condition (temperature*time) on HET of both
      species. Results showed that HET decreased non-linearly (S. avenae: 41.4-38.6
      degrees C, R. padi: 41.3-39.4 degrees C), when acclimation temperature increased
      from 25 to 36 degrees C. For both species, HET declined linearly (S. avenae: 40.1
      38.0 degrees C, R. padi: 41.3-38.5 degrees C) as acclimation time increased from
      0.5 to 6h at 35 degrees C, whereas HET descended non-linearly with reduction of
      acclimation time at 10 degrees C. HET for both species acclimated under
      constantly warm conditions (future daily temperature) were significantly lower
      than those acclimated under gradually warm conditions (current daily
      temperature). These results suggest that aphids' heat-escape behavior is
      significantly influenced by brief thermal history, implying that aphids make
      decision to avoid heat stress based on the combination of temperature and
      exposure time and escape before they were hurt by high temperatures under the
      conditions of climate warming. Avoiding high temperatures may cost a lot of time
      and resources of aphids and thus potentially reduced growth, development, and
      reproduction. Changes in insect behaviors caused by ongoing climate warming and
      their ecological consequences should be more concerned.

PMID- 21939663
TI  - The complete genome sequence of a single-stranded RNA virus from the tarnished
      plant bug, Lygus lineolaris (Palisot de Beauvois).
AB  - The complete genome sequence of a single-stranded RNA virus infecting the
      tarnished plant bug, Lygus lineolaris (Palisot de Beauvois), was identified by
      sequencing cDNA prepared from insects collected from the Mississippi Delta. The
      9655 nucleotide positive-sense single-stranded RNA genome of the L. lineolaris
      single-stranded RNA virus (LyLV-1) contained a single open reading frame of 8958
      nucleotides encoding a 2986 amino acid genome polypeptide. The open reading frame
      was flanked by untranslated regions of 603 and 69 nucleotides at the 5'- and 3'-
      ends of the genome, respectively. Database searches and homology based modeling
      was used to identify four capsid proteins (VP1-VP4), helicase/AAA-ATPase,
      cysteine protease (C3P), protease 2A, and the RNA-directed RNA polymerase (RdRp).
      In addition, a region with weak similarity to the eukaryotic structural
      maintenance of chromosome (SMC) domain was identified near the amino-terminal of
      the polyprotein and adjacent to the VP1 domain. The amino acid sequence of LyLV-1
      was approximately 44.4% similar to that of sacbrood virus (SBV) of the honey bee.
      The genomic organization of both viruses showed remarkable similarity with the
      exception of highly divergent amino acid regions flanking fairly conserved
      structural and non-structural polypeptide regions. High similarity to the SBV
      genome and similarities in the genome organization and amino acid sequence with
      the viruses of the family Iflaviridae suggested that LyLV-1 was a novel member of
      this family. Virus particles were 39 nm in diameter and appeared to transmit
      vertically via eggs. Although this virus may only cause covert infections under
      normal conditions, the potential for using this virus in biological control of L.
      lineolaris is discussed.

PMID- 21939664
TI  - Negative correlation between Nosema ceranae spore loads and deformed wing virus
      infection levels in adult honey bee workers.
AB  - Interactions between pathogens might contribute to honey bee colony losses. Here
      we investigated if there is an association between the microsporidian Nosema
      ceranae and the deformed wing virus (DWV) in different body sections of
      individual honey bee workers (Apis mellifera ligustica) under exclusion of the
      vector Varroa destructor. Our data provide correlational evidence for
      antagonistic interactions between the two pathogens in the midgut of the bees.

PMID- 21939665
TI  - Mitofusin function is dependent on the distinct tissue and organ specific roles
      of mitochondria.

PMID- 21939666
TI  - Ovariectomy enhances SR Ca2+ release and increases Ca2+ spark amplitudes in
      isolated ventricular myocytes.
AB  - This study compared Ca(2+) homeostasis in ventricular myocytes from 8-month-old
      female C57BL/6J mice that had either a bilateral ovariectomy (OVX) or a sham
      surgery at 3 weeks of age. Cells were loaded with fura-2 and field-stimulated or
      voltage-clamped with steps to membrane potentials between -40 and +80 mV (37
      degrees C). Peak Ca(2+) transients increased by two-fold in OVX myocytes when
      compared to sham, and Ca(2+) transient rates of rise and decay were faster in OVX
      cells. In contrast, Ca(2+) current densities were similar in sham and OVX cells.
      Sarcoplasmic reticulum (SR) Ca(2+) content, assessed by caffeine, also was higher
      in OVX compared to sham cells (111.7 +/- 11.9 vs. 61.2 +/- 10.4 nM; p<0.05).
      Furthermore, the gain of Ca(2+) release (Ca(2+) release/Ca(2+) current) was
      significantly greater in OVX than in sham cells (16.3 +/- 2.5 vs. 7.7 +/- 2.0
      nM/pApF(-1) at 0 mV; p<0.05). As changes in unitary Ca(2+) release might account
      for the increased gain in OVX cells, spontaneous Ca(2+) sparks were compared in
      fluo-4-loaded myocytes (37 degrees C). Spark frequency was higher in OVX cells
      than in sham cells. In addition, spark amplitudes were greater in OVX than in
      sham myocytes (DeltaF/F(0)=0.379 +/- 0.006 vs. 0.342 +/- 0.006; p<0.05). However,
      spark widths and time courses were similar in the two groups. These data suggest
      that the size of individual SR Ca(2+) release units is larger and the SR Ca(2+)
      content is greater in myocytes of OVX mice, producing augmented gain and SR
      Ca(2+) release. These observations show that OVX disrupts intracellular Ca(2+)
      homeostasis and suggest that sex steroid hormones modulate unitary Ca(2+) release
      in individual cardiac myocytes.

PMID- 21939667
TI  - Transgenic over expression of ectonucleotide triphosphate diphosphohydrolase-1
      protects against murine myocardial ischemic injury.
AB  - Modulation of purinergic signaling is critical to myocardial homeostasis.
      Ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD-1; CD39) which converts
      the proinflammatory molecules ATP or ADP to AMP is a key regulator of purinergic
      modulation. However, the salutary effects of transgenic over expression of ENTPD
      1 on myocardial response to ischemic injury have not been tested to date.
      Therefore we hypothesized that ENTPD-1 over expression affords myocardial
      protection from ischemia-reperfusion injury via specific cell signaling pathways.
      ENTPD-1 transgenic mice, which over express human ENTPDase-1, and wild-type (WT)
      littermates were subjected to either ex vivo or in vivo ischemia-reperfusion
      injury. Infarct size, inflammatory cell infiltrate and intracellular signaling
      molecule activation were evaluated. Infarct size was significantly reduced in
      ENTPD-1 versus WT hearts in both ex vivo and in vivo studies. Following ischemia
      reperfusion injury, ENTPD-1 cardiac tissues demonstrated an increase in the
      phosphorylation of the cellular signaling molecule extracellular signal-regulated
      kinases 1/2 (ERK 1/2) and glycogen synthase kinase-3beta (GSK-3beta). Resistance
      to myocardial injury was abrogated by treatment with a non-selective adenosine
      receptor antagonist, 8-SPT or the more selective A(2B) adenosine receptor
      antagonist, MRS 1754, but not the A(1) selective antagonists, DPCPX.
      Additionally, treatment with the ERK 1/2 inhibitor PD98059 or the mitochondrial
      permeability transition pore opener, atractyloside, abrogated the cardiac
      protection provided by ENTPDase-1 expression. These results suggest that
      transgenic ENTPDase-1 expression preferentially conveys myocardial protection
      from ischemic injury via adenosine A(2B) receptor engagement and associated
      phosphorylation of the cellular protective signaling molecules, Akt, ERK 1/2 and
      GSK-3beta that prevents detrimental opening of the mitochondrial permeability
      transition pore.

PMID- 21939668
TI  - Tilt-pair analysis of images from a range of different specimens in single
      particle electron cryomicroscopy.
AB  - The comparison of a pair of electron microscope images recorded at different
      specimen tilt angles provides a powerful approach for evaluating the quality of
      images, image-processing procedures, or three-dimensional structures. Here, we
      analyze tilt-pair images recorded from a range of specimens with different
      symmetries and molecular masses and show how the analysis can produce valuable
      information not easily obtained otherwise. We show that the accuracy of
      orientation determination of individual single particles depends on molecular
      mass, as expected theoretically since the information in each particle image
      increases with molecular mass. The angular uncertainty is less than 1 degrees 
      for particles of high molecular mass (~50 MDa), several degrees for particles in
      the range 1-5 MDa, and tens of degrees for particles below 1 MDa. Orientational
      uncertainty may be the major contributor to the effective temperature factor (B
      factor) describing contrast loss and therefore the maximum resolution of a
      structure determination. We also made two unexpected observations. Single
      particles that are known to be flexible showed a wider spread in orientation
      accuracy, and the orientations of the largest particles examined changed by
      several degrees during typical low-dose exposures. Smaller particles presumably
      also reorient during the exposure; hence, specimen movement is a second major
      factor that limits resolution. Tilt pairs thus enable assessment of orientation
      accuracy, map quality, specimen motion, and conformational heterogeneity. A
      convincing tilt-pair parameter plot, where 60% of the particles show a single
      cluster around the expected tilt axis and tilt angle, provides confidence in a
      structure determined using electron cryomicroscopy.

PMID- 21939669
TI  - Impairment of ubiquitin-proteasome system by E334K cMyBPC modifies channel
      proteins, leading to electrophysiological dysfunction.
AB  - Cardiac arrhythmogenesis is regulated by channel proteins whose protein levels
      are in turn regulated by the ubiquitin-proteasome system (UPS). We have
      previously reported on UPS impairment induced by E334K cardiac myosin-binding
      protein C (cMyBPC), which causes hypertrophic cardiomyopathy (HCM) accompanied by
      arrhythmia. We hypothesized that UPS impairment induced by E334K cMyBPC causes
      accumulation of cardiac channel proteins, leading to electrophysiological
      dysfunction. Wild-type or E334K cMyBPC was overexpressed in HL-1 cells and
      primary cultured neonatal rat cardiac myocytes. The expression of E334K cMyBPC
      suppressed cellular proteasome activities. The protein levels of K(v)1.5,
      Na(v)1.5, Hcn4, Ca(v)3.2, Ca(v)1.2, Serca, RyR2, and Ncx1 were significantly
      higher in cells expressing E334K cMyBPC than in wild type. They further increased
      in cells pretreated with MG132 and had longer protein decays. The channel
      proteins retained the correct localization. Cells expressing E334K cMyBPC
      exhibited higher Ca(2+) transients and longer action potential durations (APDs),
      accompanied by afterdepolarizations and higher apoptosis. Those augments of APD
      and Ca(2+) transients were recapitulated by a simulation model. Although a Ca(2+)
      antagonist, azelnidipine, neither protected E334K cMyBPC from degradation nor
      affected E334K cMyBPC incorporation into the sarcomere, it normalized the APD and
      Ca(2+) transients and partially reversed the levels of those proteins regulating
      apoptosis, thereby attenuating apoptosis. In conclusion, UPS impairment caused by
      E334K cMyBPC may modify the levels of channel proteins, leading to
      electrophysiological dysfunction. Therefore, UPS impairment due to a mutant
      cMyBPC may partly contribute to the observed clinical arrhythmias in HCM
      patients.

PMID- 21939670
TI  - The adenosine derivative 2',3',5'-tri-O-acetyl-N6-(3-hydroxylaniline) adenosine
      activates AMPK and regulates lipid metabolism in vitro and in vivo.
AB  - AIMS: Our overall objective was to investigate the effect of the adenosine
      derivative 2',3',5'-tri-O-acetyl-N6-(3-hydroxylaniline) adenosine (WS010117) on
      AMP-activated protein kinase (AMPK) activation and lipid metabolism and to also
      assess the underlying mechanisms involved in these processes. MAIN METHODS: HepG2
      cells and hamsters fed a high-fat diet were used to test the effects of WS010117
      on lipid metabolism. Western blots, chemical intervention, HPLC, SAMS peptide
      assay, (14)C-labelled acetate and palmitate assays, molecular docking assay and
      siRNA targeting the AMPK gamma1 subunit were used to investigate the effect of
      WS010117 on AMPK activation as well as the underlying mechanism involved in this
      activation. KEY FINDINGS: WS010117 treatment resulted in the dose-dependent
      activation of AMPK in HepG2 cells, increasing lipid oxidation and decreasing
      lipid biosynthesis. In hamsters that were fed a high-fat diet, WS010117 treatment
      (1.5-6 mg/kg) significantly inhibited the increase in lipid accumulation.
      WS010117-induced AMPK activation was essentially abolished by treatment with
      compound C, and the addition of WS010117 did not alter the intracellular AMP:ATP
      ratio. In HeLa cells endogenously lacking LKB1, WS010117-mediated AMPK activation
      was not impaired, even following co-treatment with STO-609, a selective inhibitor
      of Ca(2+)/calmodulin-dependent protein kinase kinase (CaMKK). The results from
      the molecular docking assays and experiments targeting the AMPK gamma1 subunit
      with siRNA indicated that WS010117 may activate AMPK by binding to and regulating
      the gamma subunit of AMPK. SIGNIFICANCE: Our data indicate that WS010117 can
      regulate lipid metabolism through the activation of AMPK. WS010117 may activate
      AMPK by binding to and regulating the AMPK gamma subunit.

PMID- 21939671
TI  - Dynamics and bifurcation of a model for hormonal control of the menstrual cycle
      with inhibin delay.
AB  - A system of 13 ordinary differential equations with 42 parameters is presented to
      model hormonal regulation of the menstrual cycle. For an excellent fit to
      clinical data, the model requires a 36 h time delay for the effect of inhibin on
      the synthesis of follicle stimulating hormone. Biological and mathematical
      reasons for this delay are discussed. Bifurcations with respect to changes in
      three important parameters are examined. One parameter represents the level of
      estradiol adequate for significant synthesis of luteinizing hormone. Bifurcation
      diagrams with respect to this parameter reveal an interval of parameter values
      for which a unique stable periodic solution exists and this solution represents a
      menstrual cycle during which ovulation occurs. The second parameter measures mass
      transfer between the first two stages of ovarian development and is indicative of
      healthy follicular growth. The third parameter is the time delay. Changes in the
      second parameter and the time delay affect the size of the uniqueness interval
      defined with respect to the first parameter. Saddle-node, transcritical and
      degenerate Hopf bifurcations are studied.

PMID- 21939672
TI  - Comparative effects in rats of intact wheat bran and two wheat bran fractions on
      the disposition of the mutagen 2-amino-3-methylimidazo[4,5-f]quinoline.
AB  - Wheat bran protects against mutations and cancer, but contains different plant
      cell types that are likely to have different protective effects. We previously
      described the production and chemical characterisation of an aleurone-rich
      fraction (ARF) and a pericarp-rich fraction (PRF) from wheat grain. We compared
      these with whole bran (WB), fed to rats as 10% of a high fat AIN-76 diet. All
      bran-supplemented diets increased faecal bulk, in the order PRF>WB>ARF. PRF
      increased the activity of NAD(P)H:quinone acceptor oxidoreductase only in the
      forestomach, whereas ARF and WB enhanced levels of glutathione S-transferase in
      the duodenum. ARF but not PRF was digested and fermented, and also encouraged
      bacterial growth. Rats were gavaged with the radioactive mutagen (14)C-labelled
      IQ (2-amino-3-methylimidazo[4,5-f]quinoline), and effects of the brans on plasma
      radioactivity measured. Compared with the control diet, all bran-supplemented
      diets reduced the concentration of radioactivity in plasma, in the order
      ARF>PRF>WB. All brans increased faecal elimination of radioactivity, but only ARF
      and PRF enhanced urinary radioactivity. These data suggest that wheat bran may
      reduce mutation and cancers through direct adsorption and enhanced elimination of
      a dietary mutagen and/or its metabolites, and that wheat bran enriched in
      pericarp or aleurone cell walls may exert protective effects through different
      mechanisms.

PMID- 21939673
TI  - The role of zinc in genomic stability.
AB  - Zinc (Zn) is an essential trace element required for maintaining both optimal
      human health and genomic stability. Zn plays a critical role in the regulation of
      DNA repair mechanisms, cell proliferation, differentiation and apoptosis
      involving the action of various transcriptional factors and DNA or RNA
      polymerases. Zn is an essential cofactor or structural component for important
      antioxidant defence proteins and DNA repair enzymes such as Cu/Zn SOD, OGG1, APE
      and PARP and may also affect activities of enzymes such as BHMT and MTR involved
      in methylation reactions in the folate-methionine cycle. This review focuses on
      the role of Zn in the maintenance of genome integrity and the effects of
      deficiency or excess on genomic stability events and cell death.

PMID- 21939674
TI  - Inhibition of iNOS induces antidepressant-like effects in mice: pharmacological
      and genetic evidence.
AB  - Recent evidence has suggested that systemic administration of non-selective NOS
      inhibitors induces antidepressant-like effects in animal models. However, the
      precise involvement of the different NOS isoforms (neuronal-nNOS and inducible
      iNOS) in these effects has not been clearly defined yet. Considering that
      mediators of the inflammatory response, that are able to induce iNOS expression,
      can be increased by exposure to stress, the aim of the present study was to
      investigate iNOS involvement in stress-induced behavioral consequences in the
      forced swimming test (FST), an animal model sensitive to antidepressant drugs.
      Therefore, we investigated the effects induced by systemic injection of
      aminoguanidine (preferential iNOS inhibitor), 1400W (selective iNOS inhibitor) or
      n-propyl-l-arginine (NPA, selective nNOS inhibitor) in mice submitted to the FST.
      We also investigated the behavior of mice with genetic deletion of iNOS
      (knockout) submitted to the FST. Aminoguanidine significantly decreased the
      immobility time (IT) in the FST. 1400W but not NPA, when administered at
      equivalent doses considering the magnitude of their Ki values for iNOS and nNOS,
      respectively, reduced the IT, thus suggesting that aminoguanidine-induced effects
      would be due to selective iNOS inhibition. Similarly, iNOS KO presented decreased
      IT in the FST when compared to wild-type mice. These results are the first to
      show that selective inhibition of iNOS or its knockdown induces antidepressant
      like effects, therefore suggesting that iNOS-mediated NO synthesis is involved in
      the modulation of stress-induced behavioral consequences. Moreover, they further
      support NO involvement in the neurobiology of depression. This article is part of
      a Special Issue entitled 'Anxiety and Depression'.

PMID- 21939675
TI  - Regional differences in cerebral asymmetries of human cortical white matter.
AB  - The form of the structural asymmetries across the cerebral hemispheres, that
      support well-established functional asymmetries, are not well understood.
      Although, many previous studies have investigated structural differences in areas
      associated with strong functional asymmetries, such as language processes,
      regions of the brain with less well established functional laterality have
      received less attention. The current study aims to address this by exploring
      global white matter asymmetries of the healthy human brain using diffusion tensor
      imaging (DTI) and tractography. DTI was conducted on twenty-nine healthy right
      handed males, and pathways from the four major lobes were reconstructed using
      probabilistic tractography. Mean FA, parallel and perpendicular diffusion values
      were calculated and compared across hemispheres for each pathway generated.
      Significant asymmetries in the parietal (rightward asymmetry) and occipital
      (leftward asymmetry) pathways were found in FA measures. However, asymmetric
      patterns in parallel and/or perpendicular diffusion were observed in all four
      lobes, even in pathways with symmetrical FA. For instance, significant rightward
      asymmetry in parallel diffusion was found in the parietal and frontal lobes,
      whereas significant leftward asymmetry was found in the temporal and occipital
      lobes. We suggest that these different patterns of diffusion asymmetry reflect
      differences in microanatomy that support the known patterns of differential
      functional asymmetry. The different directions of anatomical asymmetry support
      the notion that there may be a number of different lateralising influences
      operating in the brain.

PMID- 21939676
TI  - Faster, stronger, lateralized: low spatial frequency information supports face
      processing.
AB  - Distinct visual pathways are selectively tuned for processing specific spatial
      frequencies. Recently, Awasthi, Friedman, and Williams (2011) reported fast
      categorisation of faces at periphery, arguing for primacy of low spatial
      frequency (LSF) information in face processing. However, previous studies have
      also documented rapid categorization of places and natural scenes. Here, we
      tested if the LSF advantage is face specific or also involved in place
      perception. We used visually guided reaching as a continuous behavioral measure
      to examine the processing of LSF and high spatial frequency (HSF) hybrids,
      presented at the periphery. Subjects reached out and touched targets and their
      movements were recorded. The trajectories revealed that LSF interference was both
      95 ms earlier and stronger for faces than places and was lateralized to the left
      visual field. The early processing of LSF information supports the assumption
      that faces are prioritised and provides a (neural) framework for such specialised
      processing.

PMID- 21939677
TI  - The brain dynamics of intellectual development: waxing and waning white and gray
      matter.
AB  - Distributed brain areas support intellectual abilities in adults. How structural
      maturation of these areas in childhood enables development of intelligence is not
      established. Neuroimaging can be used to monitor brain development, but studies
      to date have typically considered single imaging modalities. To explore the
      impact of structural brain maturation on the development of intelligence, we used
      a combination of cortical thickness, white matter (WM) volume and WM
      microstructure in 168 healthy participants aged 8-30 years. Principal component
      analyses (PCAs) were conducted separately for cortical thickness, WM volume,
      fractional anisotropy (FA) and mean diffusivity (MD) in 64 different brain
      regions. For all four parameters, the PCAs revealed a general factor explaining
      between 40% and 53% of the variance across regions. When tested separately,
      negative age-independent relationships were found between intellectual abilities
      and cortical thickness and MD, respectively, while WM volume and FA were
      positively associated with intellectual abilities. The relationships between
      intellectual abilities and brain structure varied with age, with stronger
      relationships seen in children and adolescents than in young adults. Multiple
      regression analysis with the different imaging measures as simultaneous
      predictors, showed that cortical thickness, WM volume and MD all yielded unique
      information in explaining intellectual abilities in development. The present
      study demonstrates that different imaging modalities and measures give
      complementary information about the neural substrates of intellectual abilities
      in development, emphasizing the importance of multimodal imaging in
      investigations of neurocognitive development.

PMID- 21939678
TI  - Meaningful physical changes mediate lexical-semantic integration: top-down and
      form-based bottom-up information sources interact in the N400.
AB  - Models of how the human brain reconstructs an intended meaning from a linguistic
      input often draw upon the N400 event-related potential (ERP) component as
      evidence. Current accounts of the N400 emphasise either the role of contextually
      induced lexical preactivation of a critical word (Lau, Phillips, & Poeppel, 2008)
      or the ease of integration into the overall discourse context including a wide
      variety of influencing factors (Hagoort & van Berkum, 2007). The present ERP
      study challenges both types of accounts by demonstrating a contextually
      independent and purely form-based bottom-up influence on the N400: the N400
      effect for implausible sentence-endings was attenuated when the critical sentence
      final word was capitalised (following a lowercase sentence context). By contrast,
      no N400 modulation occurred when the critical word involved a change from
      uppercase (sentence context) to lowercase. Thus, the N400 was only affected by a
      change to uppercase letters, as is often employed in computer-mediated
      communication as a sign of emphasis. This result indicates that N400 amplitude is
      reduced for unexpected words when a bottom-up (orthographic) cue signals that the
      word is likely to be highly informative. The lexical-semantic N400 thereby
      reflects the degree to which the semantic informativity of a critical word
      matches expectations, as determined by an interplay between top-down and bottom
      up information sources, including purely form-based bottom-up information.

PMID- 21939679
TI  - Relearning in semantic dementia reflects contributions from both medial temporal
      lobe episodic and degraded neocortical semantic systems: evidence in support of
      the complementary learning systems theory.
AB  - When relearning words, patients with semantic dementia (SD) exhibit a
      characteristic rigidity, including a failure to generalise names to untrained
      exemplars of trained concepts. This has been attributed to an over-reliance on
      the medial temporal region which captures information in sparse, non-overlapping
      and therefore rigid representations. The current study extends previous
      investigations of SD relearning by re-examining the additional contribution made
      by the degraded cortical semantic system. The standard relearning protocol was
      modified by careful selection of foils to show that people with semantic dementia
      were sometimes able to extend their learning appropriately but that this correct
      generalisation was minimal (i.e. the patients under-generalised their learning).
      The revised assessment procedure highlighted the fact that, after relearning, the
      participants also incorrectly over-generalised the learned label to closely
      related concepts. It is unlikely that these behaviours would occur if the
      participants had only formed sparse hippocampal representations. These novel data
      build on the notion that people with semantic dementia engage both the degraded
      cortical semantic (neocortex) and the episodic (medial temporal) systems to
      learn. Because of neocortical damage to the anterior temporal lobes, relearning
      is disordered with a characteristic pattern of under- and over-generalisation.

PMID- 21939680
TI  - 'Winner effect' without winning: unresolved social conflicts increase the
      probability of winning a subsequent contest in a cichlid fish.
AB  - Previous winning experience increases the probability of winning a subsequent
      contest. However, it is not clear whether winning probability is affected only by
      the outcome of the contest (winning or losing) or whether fighting experience
      itself is also sufficient to induce this effect. We investigated this question in
      the East African cichlid fish Pundamilia spec. To create an unresolved conflict
      we allowed males to fight their own mirror image prior to a real fight against a
      size-matched non-mirror-stimulated control male. When males fight their own
      mirror image, the image's response corresponds to the action of the focal animal,
      creating symmetrical fighting conditions without the experience of losing or
      winning. We found that mirror-stimulated males were more likely to win an ensuing
      contest than control males. Interestingly, in this species mirror stimulation
      also induced an increase in circulating androgens, which is consistent with the
      hypothesis that stimulation of these sex steroids during aggressive encounters
      may prepare the animal for subsequent encounters. Our results suggest that
      fighting experience alone coupled with an androgen response, increases the
      likelihood of winning, even in the absence of a winning experience.

PMID- 21939681
TI  - Maternal obesity, metabolic disease, and allostatic load.
AB  - Maternal obesity is a risk factor for many metabolic diseases for the mother,
      both during gestation and post partum, and for the child in later life. Obesity
      and pregnancy both result in altered physiological states, significantly
      different from the state of the non-obese, non-reproductive adult female. The
      concept of allostasis may be more appropriate for understanding the physiology of
      both pregnancy and obesity. In pregnancy these altered physiological states are
      adaptive, in both the evolutionary and physiological senses of the word. Obesity,
      however, represents a state outside of the adaptive evolutionary experience of
      our species. In both cases the altered physiological state derives at least in
      part from signals from an active endocrine organ. In obesity this is adipose
      tissue, and in pregnancy it is the placenta. The signaling molecules from adipose
      tissue and placenta all have multiple functions and can affect multiple organ
      systems. Placenta acts as a central regulator of metabolism for both the maternal
      and fetal compartments, in essence acting as a "third brain" during pregnancy.
      Both adipose tissue and placenta express many proinflammatory cytokines; obesity
      and pregnancy are states of low-grade inflammation. Both obesity and pregnancy
      are also states of insulin resistance, and maternal obesity is associated with
      fetal insulin resistance. We argue that obesity during pregnancy leads to
      sustained and inappropriate activation of normally adaptive regulatory circuits
      due in part to competing and conflicting signaling from adipose tissue and
      placenta. This results in allostatic load, leading to the eventual break down of
      regulatory mechanisms. The result is impaired metabolic function of the mother,
      and altered development of metabolic systems and potentially altered neural
      appetite circuits for the offspring.

PMID- 21939683
TI  - Trends in roll-your-own tobacco use among adolescents in Finland, 1981-2009.

PMID- 21939682
TI  - Characterization of a venom peptide from a crassispirid gastropod.
AB  - The crassispirids are a large branch of venomous marine gastropods whose venoms
      have not been investigated previously. We demonstrate that crassispirids comprise
      a major group of toxoglossate snails in a clade distinct from all turrids whose
      venoms have been analyzed. The isolation and biochemical definition of the first
      venom component from any crassispirid is described. Crassipeptide cce9a from
      Crassispira cerithina (Anton, 1838) was purified from crude venom by following
      biological activity elicited in young mice, lethargy and a lack of responsiveness
      to external stimuli. Using Edman sequencing and mass spectrometry, the purified
      peptide was shown to be 29 amino acid residues long, with the sequence:
      GSCGLPCHENRRCGWACYCDDGICKPLRV. The sequence assignment was verified through the
      analysis of a cDNA clone encoding the peptide. The peptide was chemically
      synthesized and folded; the synthetic peptide was biologically active and
      coelution with the native venom peptide was demonstrated. When injected into mice
      of various ages, the peptide elicited a striking shift in behavioral phenotype
      between 14 and 16 days, from lethargy to hyperactivity.

PMID- 21939684
TI  - Longitudinal changes in weight in relation to smoking cessation in participants
      of the EPIC-PANACEA study.
AB  - PURPOSE: We assessed the association between smoking cessation and prospective
      weight change in the European population of the European Prospective
      Investigation into Cancer and Nutrition-Physical Activity, Nutrition, Alcohol,
      Cessation of smoking, Eating out of home And obesity (EPIC-PANACEA) project.
      METHODS: The study involved more than 300,000 healthy volunteers, recruited
      between 1992 and 2000 in 9 European countries, who provided data on anthropometry
      and smoking habits at baseline and after a follow-up of 5 years on average.
      Adjusted mixed-effects linear regression models were used to obtain sex-specific
      summary estimates of the association between the change in smoking status and the
      annual change in weight. RESULTS: Smoking cessation tends to be followed by
      weight gain; when compared to stable smokers, annual weight gain was higher in
      men (0.44 kg (95%CI: 0.36; 0.52)) and women (0.46 kg (95%CI: 0.41; 0.52)) who
      stopped smoking during follow-up. When smokers who stopped smoking at least 1
      year before recruitment were compared to never smokers, no major differences in
      annual weight gain were observed. The excess weight gain following smoking
      cessation appears to mainly occur in the first years following the cessation.
      CONCLUSIONS: When considering the benefits of smoking cessation, such findings
      strengthen the need for promoting cessation offering information on weight gain
      control and support to weight-concerned smokers in order to remove a barrier to
      quitting.

PMID- 21939685
TI  - Variability of cell wall polysaccharides composition and hemicellulose enzymatic
      profile in an apple progeny.
AB  - The genetic variability of apple cell walls polysaccharides chemical composition
      and structure was assessed in a progeny of 141 individuals harvested over 2
      years. The variability of the hemicelluloses oligosaccharides released by
      glucanase was analyzed by MALDI-TOF MS. The genetic contribution was
      distinguished from harvest year as well as from parental crossing patterns and
      scab resistance selection. Results showed that harvest year had a major impact on
      cell wall polysaccharide composition and structure. Within each harvest, genetic
      effect impact more significantly cell wall polysaccharide chemistry than does
      reciprocal crossing or early scab selection. Uronic acids, glucose, galactose and
      xylose contents as well as some glucomannan and xyloglucan structures have a high
      heritability. This first cell wall chemotyping of an apple progeny opens the way
      for future searches of genetic markers for the chemical variability of cell wall
      polysaccharides.

PMID- 21939686
TI  - Electrochemical spectroscopic investigations on the interaction of an ytterbium
      complex with DNA and their analytical applications such as biosensor.
AB  - Metal ion-DNA interactions are important in nature, often changing the genetic
      material's structure and function. A new Yb complex of YbCl(3) (tris(8
      hydroxyquinoline-5-sulfonic acid) ytterbium) was synthesized and utilized as an
      electrochemical indicator for the detection of DNA oligonucleotide based on its
      interaction with Yb(QS)(3). Cyclic voltammetry (CV) and fluorescence spectroscopy
      were used to investigate the interaction of Yb(QS)(3) with ds-DNA. It was
      revealed that Yb(QS)(3) presented an excellent electrochemical activity on glassy
      carbon electrode (GCE) and could intercalate into the double helix of double
      stranded DNA (ds-DNA). The binding mechanism of interaction was elucidated on
      glassy carbon electrode dipped in DNA solution and DNA modified carbon paste
      electrode by using differential pulse voltammetry and cyclic voltammetry. The
      binding ratio between this complex and ds-DNA was calculated to be 1:1. The
      extent of hybridization was evaluated on the basis of the difference between
      signals of Yb(QS)(3) with probe DNA before and after hybridization with
      complementary DNA. With this approach, this DNA could be quantified over the
      range from 1 * 10(-8) to 1.1 * 10(-7)M. The interaction mode between Yb(QS)(3)
      and DNA was found to be mainly intercalative interaction. These results were
      confirmed with fluorescence experiments.

PMID- 21939687
TI  - Rotavirus in adults requiring hospitalization.
AB  - OBJECTIVES: To determine the prevalence and epidemiological characteristics of
      rotavirus among adults admitted to the hospital with diarrhea that have bacterial
      stool cultures sent. METHODS: The prevalence of rotavirus was determined by
      Rotaclone EIA in samples submitted for bacterial stool culture from adults
      requiring hospitalization at Northwestern Memorial Hospital, Chicago from
      December 01, 2005-November 30, 2006. RESULTS: Rotavirus was detected in 2.9% of
      eligible bacterial stool cultures. A bacterial pathogen (e.g., Salmonella,
      Shigella, Campylobacter) was identified in 3.3%. Bacterial stool pathogens were
      more common from June-October while rotavirus was 2.4 times more common than all
      bacterial pathogens from February-May. Adults in whom rotavirus was detected were
      older (p < 0.05) and more often immunosuppressed (p < 0.02), particularly with
      HIV (p < 0.04) compared to individuals from whom bacteria were isolated. The
      duration of hospitalization and the number of invasive procedures performed in
      those with rotavirus and bacterial diarrhea were comparable. CONCLUSIONS: In the
      era immediately prior to widespread rotavirus vaccination of children, rotavirus
      was as commonly detected from adults admitted to the hospital with diarrhea as
      are the bacterial gastroenteritis pathogens. Rotavirus is particularly prevalent
      from February-May (as in children) and in immunosuppressed or older adults.

PMID- 21939688
TI  - In vivo imaging of epileptic activity using 2-NBDG, a fluorescent deoxyglucose
      analog.
AB  - Accurately locating epileptic foci has great importance in advancing the
      treatment of epilepsy. In this study, epileptic seizures were first induced by
      intracortical injection of 4-aminopyridine in rats. A fluorescent deoxyglucose
      substitute, 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2
      NBDG), was then continuously injected via the tail vein. Brain glucose metabolism
      was subsequently monitored by fluorescence imaging of 2-NBDG. The initial uptake
      rate of 2-NBDG at the injection site of 4-aminopyridine significantly exceeded
      that of the control injection site, which indicated local hypermetabolism induced
      by seizures. Our results show that 2-NBDG can be used for localizing epileptic
      foci.

PMID- 21939689
TI  - Development and evaluation of an automatable focus reduction neutralisation test
      for the detection of measles virus antibodies using imaging analysis.
AB  - A plaque reduction neutralisation test (PRNT) is still regarded as the gold
      standard for the investigation of anti-measles immunity. In this study, an
      alternative simplified automatable focus reduction neutralisation test (AFRNT)
      based on the classical PRNT was developed. The AFRNT uses the conventional
      Edmonston strain of measles, immunoperoxidase staining with monoclonal
      antibodies, and automated plaque counts performed with AID ViruSpot software. The
      assay is performed in 96-well plates, requires 2 days, and is fully automatable.
      The AFRNT was evaluated in comparison with PRNT and Enzygnost anti-measles enzyme
      immunoassay (EIA). A total of 130 samples, which included two available WHO
      international anti-measles standards, sera from 90 patients, and 38 different
      lots of immunoglobulin products, were tested. Overall, good agreement was
      observed between EIA and both neutralisation tests; however, the EIA values for
      the immunoglobulin products and international standards were slightly but
      significantly higher than those of the neutralisation tests. The Bland-Altman
      analysis showed excellent agreement between AFRNT and PRNT. AFRNT is a fully
      automatable high-throughput neutralisation assay, which can be performed with
      measles and other types of viruses, including wild-type strains. It is perfectly
      suited for epidemiological and vaccine studies.

PMID- 21939690
TI  - Nanobodies(r): new ammunition to battle viruses.
AB  - In 1989, a new type of antibody was identified, first in the sera of dromedaries
      and later also in all other species of the Camelidae family. These antibodies do
      not contain a light chain and also lack the first constant heavy domain. Today it
      is still unclear what the evolutionary advantage of such heavy chain-only
      antibodies could be. In sharp contrast, the broad applicability of the isolated
      variable antigen-binding domains (VHH) was rapidly recognized, especially for the
      development of therapeutic proteins, called Nanobodies((r)). Here we summarize
      first some of the unique characteristics and features of VHHs. These will next be
      described in the context of different experimental therapeutic applications of
      Nanobodies against different viruses: HIV, Hepatitis B virus, influenza virus,
      Respiratory Syncytial virus, Rabies virus, FMDV, Poliovirus, Rotavirus, and
      PERVs. Next, the diagnostic application of VHHs (Vaccinia virus, Marburg virus
      and plant Tulip virus X), as well as an industrial application (lytic lactococcal
      936 phage) will be described. In addition, the described data show that
      monovalent Nanobodies can possess unique characteristics not observed with
      conventional antibodies. The straightforward formatting into bivalent,
      multivalent, and/or multispecific Nanobodies allowed tailoring molecules for
      potency and cross-reactivity against viral targets with high sequence diversity.

PMID- 21939691
TI  - Comparison of rat sensory behavioral tasks to detect somatosensory morbidity
      after diffuse brain-injury.
AB  - Brain injury disrupts neuronal circuits, impacting neurological function.
      Selective and sensitive behavioral tests are required to explore neurological
      dysfunction, recovery and potential therapy. Previously we reported that the
      Whisker Nuisance Task (WNT), where whiskers are manually stimulated in an open
      field, shows sensory sensitivity in diffuse brain-injured rats. To further
      explore this somatosensory morbidity, we evaluated three additional whisker
      dependent tasks: Gap Cross Test, a novel Angle Entrance Task and Whisker Guided
      Exploration Task. Brain-injured (n=11) and sham (n=8) rats were tested before
      midline fluid percussion brain injury (moderate: 2.0atm) and 1 and 4 weeks after
      injury. For the WNT, we confirmed that brain-injured rats develop significant
      sensory sensitivity to whisker stimulation over 28 days. In the Gap Cross Test,
      where rats cross progressively larger elevated gaps, we found that animals were
      inconsistent in crossable distance regardless of injury. In the Angle Entrance
      Task, where rats enter 30 degrees , 40 degrees , 50 degrees  or 80 degrees 
      corners, rats performed consistently regardless of injury. In the Whisker Guided
      Exploration Task, where rats voluntarily explore an oval circuit, we identified
      significant decreases in the number of rears and reversals and changes in the
      predominant location (injured rats spend more time in the inside of the turn
      compared to the outside) after injury and increased thigmotaxis after sham and
      brain-injury. Both the WNT and Whisker Guided Exploration Task show injury
      induced somatosensory behavioral morbidity; however, the WNT remains more
      sensitive in detecting brain injury, possibly due to imposed whisker stimulation
      that elicits agitation similar to the human condition.

PMID- 21939692
TI  - The relationship between corticospinal excitability during motor imagery and
      motor imagery ability.
AB  - It is commonly reported that transcranial magnetic stimulation (TMS) of the motor
      cortex during action observation and motor imagery results in increases in the
      amplitude of motor evoked potentials (MEPs) in muscles specific to the observed
      or imagined action. This study aimed to determine whether MEP amplitude was
      related to the motor imagery ability of participants. Participants were 15
      healthy, right-handed adults (five male), with a mean age of 29.7 years. Motor
      imagery ability was measured using the Vividness of Movement Imagery
      Questionnaire-2 (VMIQ-2) and a hand rotation task. TMS was delivered during
      observation and imagery of a finger-thumb opposition sequence and MEPs were
      measured in the abductor pollicis brevis. Significant increases in MEP amplitude,
      from baseline, were recorded during observation and imagery conditions. The
      change in amplitude to both observation and imagery was expressed as a percentage
      of baseline amplitude. There was a significant correlation between MEP change for
      the imagery condition and imagery ability, with greater change linked to more
      vivid images and faster response times. The relationship between MEP change for
      the observation condition and imagery ability was less salient. This is the first
      study to show that the strength of corticospinal activation during imagery, which
      may be a determinant of the effectiveness of imagery training, is related to
      imagery ability in the general population, and has implications for clinical
      programs.

PMID- 21939693
TI  - A high-throughput assay for the identification of drugs against late-stage
      Plasmodium falciparum gametocytes.
AB  - Recent success in the global reduction campaign against malaria has resulted in
      the possibility that it may be feasible to drastically reduce or even eradicate
      malaria even without the introduction of a vaccine. However, while there has been
      significant effort to design the next generation of antimalarial drugs, one area
      that is underrepresented in the current antimalarial pharmacopeia is that of
      transmission blocking drugs directed at late-stage gametocytes. Here we describe
      the development of a robust and simple assay that is amenable to a high
      throughput format for the discovery of new antigametocyte drugs.

PMID- 21939694
TI  - An in vitro urinary tract catheter system to investigate biofilm development in
      catheter-associated urinary tract infections.
AB  - Biofilm development in urinary tract catheters is an often underestimated
      problem. However, this form of infection leads to high mortality rates and causes
      significant costs in health care. Therefore, it is important to analyze these
      biofilms and establish avoiding strategies. In this study a continuous flow
      through system for the cultivation of biofilms under catheter-associated urinary
      tract infection conditions was established and validated. The in vitro urinary
      tract catheter system implies the composition of urine (artificial urine medium),
      the mean volume of urine of adults (1 mL min(-1)), the frequently used silicone
      catheter (foley silicon catheter) as well as the infection with uropathogenic
      microorganisms like Pseudomonas aeruginosa. Three clinical isolates from urine of
      catheterized patients were chosen due to their ability to form biofilms, their
      mobility and their cell surface hydrophobicity. As reference strain P. aeruginosa
      PA14 has been used. Characteristic parameters as biofilm thickness, specific
      biofilm growth rate and substrate consumption were observed. Biofilm thicknesses
      varied from 105+/-16 MUm up to 246+/-67 MUm for the different isolates. The
      specific biofilm growth rate could be determined with a non invasive optical
      biomass sensor. This sensor allows online monitoring of the biofilm growth in the
      progress of the cultivation.

PMID- 21939695
TI  - A qNMR approach for bitterness phenotyping and QTL identification in an F1
      apricot progeny.
AB  - In apricot the bitter flavor of seeds is determined by the amount of amygdalin, a
      cyanogenic glucoside whose cleavage by endogenous enzymes, upon seed crushing,
      releases toxic hydrogen cyanide. The presence of such a poisonous compound is an
      obstacle to the use and commercialization of apricot seeds for human or animal
      nutrition. To investigate the genetic loci involved in the determination of the
      bitter phenotype a combined genetic and biochemical approach was used, involving
      a candidate gene analysis and a fine phenotyping via quantitative nuclear
      magnetic resonance, on an F1 apricot progeny. Seven functional markers were
      developed and positioned on the genetic maps of the parental lines Lito and
      BO81604311 and seven putative QTLs for the bitterness level were determined. In
      conclusion, this analysis has revealed some loci involved in the shaping of the
      bitterness degree; has proven the complexity of the bitter trait in apricot,
      reporting an high variance of the QTLs found over the years; has showed the
      critical importance of the phenotyping step, whose precision and accuracy is a
      pre-requisite when studying such a multifactorial character.

PMID- 21939696
TI  - Unstable steady state operations of substrate inhibited cultures by dissolved
      oxygen control.
AB  - Microorganism kinetic growth characterized by substrate inhibition was
      investigated by means of a continuous stirred tank reactor equipped with a
      feedback controller of the medium feeding flow rate. The aerobic growth of
      Pseudomonas sp. OX1 with phenol as carbon/energy source was adopted as a case
      study to test a new control strategy using dissolved oxygen concentration as a
      state variable. The controller was successful in steadily operating bioconversion
      under intrinsically unstable conditions. A simple model of the controlled system
      was proposed to set the feedback controller. The specific growth rate of
      Pseudomonas sp. OX1 was successfully described by means of the Haldane model. The
      regression of the experimental data yielded MU(M)=0.26 h(-1), K(Ph)=5*10(-3)g/L
      and K(I)=0.2g/L. The biomass-to-substrate fractional yield as a function of the
      specific growth rate did not change moving from substrate-inhibited to substrate
      deficient state. The data was modelled according to the Pirt model: m=1.7*10(
      2)g/(gh), Y(X/Ph)(Th)=1.3g/g. The specific growth rates calculated for batch and
      continuous growth were compared.

PMID- 21939697
TI  - Treatment of mezcal vinasses: a review.
AB  - Mexican distilleries produce near eight million liters of mezcal per year, and
      generate about 90 million liters of mezcal vinasses (MV). This acidic liquid
      waste is very aggressive to the environment because of its high content of toxic
      and recalcitrant organic matter. As a result, treatment is necessary before
      discharge to water bodies. It is interesting, yet disturbing; verify that there
      is a significant gap on the treatment of MV. However, there is an abundant body
      of research on treatment of other recalcitrant toxic effluents that bear some
      similarity to MV, for example, wine vinasse, vinasses from the sugar industry,
      olive oil, and industrial pulp and paper wastewaters. The objective of this
      review is to critically organize the treatment alternatives of MV, assess their
      relative advantages and disadvantages, and finally detect the trends for future
      research and development. Experience with treatment of this set of residuals,
      indicates the following trends: (i) anaerobic digestion, complemented by
      oxidative chemical treatments (e.g. ozonation) are usually placed as
      pretreatments, (ii) aerobic treatment alone and combined with ozone which have
      been directed to remove phenolic compounds and color have been successfully
      applied, (iii) physico-chemical treatments such as Fenton, electro-oxidation,
      oxidants and so on., which are now mostly at lab scale stage, have demonstrated a
      significant removal of recalcitrant organic compounds, (iv) fungal pretreatment
      with chemical treatment followed by oxidative (O(3)) or anaerobic digestion, this
      combination seems to give attractive results, (v) vinasses can be co-composted
      with solid organic wastes, particularly with those from agricultural activities
      and agro-industies; in addition to soil amenders with fertilizing value to
      improve soil quality in typical arid lands where agave is cultivated, it seems to
      be a low cost technology very well suited for rural regions in underdeveloped
      countries where more sophisticated technologies are difficult to adopt, due to
      high costs and requirements of skilled personnel.

PMID- 21939698
TI  - Changes in bacterial communities from anaerobic digesters during petroleum
      hydrocarbon degradation.
AB  - Anaerobic biodegradation of petroleum hydrocarbons (PHC) to methane has been
      recognized to occur in oil reservoirs and contaminated surface sites alike. This
      process could be employed efficiently for the treatment of contaminated
      materials, including petrochemical wastes and PHC-contaminated soil, since no
      external electron acceptor is required. Moreover, the controlled production of
      methane in digestion plants, similarly to the anaerobic digestion (AD) of energy
      crops or organic residues, would enable for energy recovery from these wastes. At
      present, little is known about the bacterial communities involved in and
      responsible for hydrocarbon fermentation, the initial step in PHC conversion to
      methane. In the present study, the fate of two different methanogenic communities
      derived from the AD of wastewater (WWT) and of biowaste, mixed with PHC
      contaminated soil (SWT), was monitored during incubation with PHC using
      denaturing gradient gel electrophoresis (DGGE) of 16S rDNA genes amplified with
      Bacteria-specific primers. During 11 months of incubation, slight but significant
      degradation of PHC occurred in both sludges and distinct bacterial communities
      were developing. In both sludges, Bacteroidetes were found. In addition, in WWT,
      the bacterial community was found to be dominated by Synergistetes and
      Proteobacteria, while Firmicutes and unidentified members were abundant in SWT.
      These results indicate that bacterial communities from anaerobic digesters can
      adapt to and degrade petroleum hydrocarbons. The decontamination of PHC
      containing waste via fermentative treatment appears possible.

PMID- 21939699
TI  - Characterization of microbial communities during anode biofilm reformation in a
      two-chambered microbial electrolysis cell (MEC).
AB  - GeoChip (II) and single strand conformation polymorphism (SSCP) were used to
      characterize anode microbial communities of a microbial electrolysis cell (MEC).
      Biofilm communities, enriched in a two-chamber MEC (R1, 0.6 V applied) having a
      coulombic efficiency (CE) of 35+/-4% and a hydrogen yield (Y(H2))of 31+/-3%, were
      used as the inoculum for a new reactor (R2). After three months R2 achieved
      stable performance with CE=38+/-4% and (Y(H2)). Few changes in the predominant
      populations were observed from R1 to R2. Unlike sludge inoculation process in R1
      in the beginning, little further elimination was aroused by community
      competitions in anode biofilm reformation in R2. Functional genes detection of
      biofilm indicated that cytochrome genes enriched soon in new reactor R2, and four
      genera (Desulfovibrio, Rhodopseudomonas, Shewanella and Geobacter) were likely to
      contribute to exoelectrogenic activity. This work also implied that symbiosis of
      microbial communities (exoelectrogens and others) contribute to system
      performance and stability.

PMID- 21939700
TI  - Thermally-triggered 'off-on-off' response of gadolinium-hydrogel-lipid hybrid
      nanoparticles defines a customizable temperature window for non-invasive magnetic
      resonance imaging thermometry.
AB  - For effective and safe thermotherapy, real-time, accurate, three-dimensional
      tissue thermometry is required. Magnetic resonance imaging (MRI)-based
      thermometry in combination with current temperature responsive contrast agents
      only provides an 'off-on' signal at a certain temperature, not indicating
      temperature increases beyond the desired therapeutic levels. To overcome this
      limitation, a novel Gd-chelated hydrogel-lipid hybrid nanoparticle (HLN)
      formulation was developed that provides an 'off-on-off' signal defining a
      thermometric window for MR thermometry. Novel thermally responsive poly(N
      isopropylacrylamide-co-acrylamide) (NIPAM-co-AM) hydrogel nanoparticles (<15 nm)
      with bisallylamidodiethylenetriaminetriacetic acid, a novel crosslinker with
      Gd(3+) chelation functionality, were synthesized. The Gd-hydrogel nanoparticles
      were encapsulated in a solid lipid nanoparticle matrix that prevented T(1)
      weighted contrast signal enhancement. Melting of the matrix lipid freed the Gd
      hydrogel nanoparticles into the bulk water and an 'off-on' contrast signal
      enhancement occurred. As the temperature was further increased to temperatures
      greater than, the volume phase transition temperature of the hydrogel
      nanoparticles, they collapsed and provided an 'on-off' signal diminution. Both
      the 'off-on' and the 'on-off' transition temperature could be tailored by
      changing the lipid matrix and altering the NIPAM/AM ratio in the hydrogel,
      respectively. This allowed MRI thermometry of different temperature windows using
      the Gd-HLN system.

PMID- 21939701
TI  - Release of vancomycin from multilayer coated absorbent gelatin sponges.
AB  - Wounds have the potential to become infected during any surgical procedure.
      Gelatin sponges that are commonly used to absorb blood during invasive surgeries
      would benefit tremendously if they released antibiotics. In this work, we have
      examined coating a commercial gelatin sponge with degradable polymer multilayer
      films containing vancomycin. The effect of the film on sponge absorption
      capabilities and the effect of the sponge on drug release kinetics were both
      examined. Application of vancomycin containing layer-by-layer assembled films to
      this highly porous substrate greatly increased drug loading up to approximately
      880% compared to a flat substrate. Vancomycin drug release was extended out to 6
      days compared to 2 days for film coated flat substrates. Additionally, the
      absorbent properties of the gelatin sponge were actually enhanced by up to 170%
      due to the presence of the vancomycin film coating. A comparison of film coated
      sponges with sponges soaked directly in vancomycin demonstrated the ability of
      the multilayer films to control drug release. Film released vancomycin was also
      found to remain highly therapeutic with unchanged antimicrobial properties
      compared to the neat drug, demonstrated by quantifying vancomycin activity
      against Staphylococcus aureus in vitro.

PMID- 21939702
TI  - A new biodegradable adhesive for protection of intestinal anastomoses.
      Preliminary communication.
AB  - BACKGROUND AND AIMS: Anastomotic leaks continue to be a devastating complication
      for patients and surgeons worldwide. The few surgical adhesives available to date
      have not achieved the desired clinical results. The purpose of this experimental
      study was to determine if Pebisut(r) applied to intestinal suture lines provides
      increased resistance and protection during the critical days of healing. METHODS:
      Intestinal lesions were caused in rats and dogs and a new biodegradable adhesive
      (Pebisut(r)) (patent granted in the European Union 07808494.4-1219, 01.12.2010,
      in Mexico P.C.T./MX/a/2009/001737, 16.02.2009, pending in the U.S.P.T.O.
      60/762,136, 26.01.2006) was applied to compare the resistance of suture lines
      using bursting pressures and histologically. RESULTS: Under acute and chronic
      conditions, Pebisut(r) strengthened and made the suture lines more resistant,
      while histologically penetrating and sealing them. The adhesive disappears within
      2-3 weeks and is well tolerated by the intestinal tissues. CONCLUSIONS: This
      biodegradable adhesive provides greater resistance, temporarily protects suture
      lines and may prevent anastomotic leaks.

PMID- 21939704
TI  - The evolution of pro-opiomelanocortin: looking for the invertebrate fingerprints.
AB  - The presence and role of the pro-opiomelanocortin (POMC) gene and encoded
      peptides in invertebrates are here summarized and discussed. Some of the POMC
      derived peptides show a significant similarity regarding their functions,
      suggesting their appearance before the split of protostomian-deuterostomian
      lineages and their maintenance during evolution. The basic mechanisms that govern
      the exchange of information between cells are usually well conserved, and this
      could have also been for POMC-derived peptides, that are mainly involved in
      fundamental functions such as immune and neuroendocrine responses. However, the
      presence and functions that POMC-derived peptides exhibit in taxonomically
      distant models, are not always reflected by the expected gene homology, leaving
      the problem of POMC evolution in invertebrates in need of additional study.

PMID- 21939703
TI  - Amylin effect in extrapancreatic tissues participating in glucose homeostasis, in
      normal, insulin-resistant and type 2 diabetic state.
AB  - Amylin is co-secreted with insulin, responds to the same stimuli, is anorectic,
      lowers body weight by reducing fat mass, and is proposed for diabetes treatment.
      We examined the effect of a 3-day constant infusion of close to physiological
      doses of amylin in Wistar rats, on glucotransporter expression, glycogen content
      (G), glycogen synthase a activity (GSa) and glucose transport (GT), in liver,
      muscle and fat from insulin resistant (IR) and type 2 diabetic (T2D) models,
      compared to normal (N) animals; plasma glucose and insulin were measured. Plasma
      insulin in IR was higher than in N or T2D, and amylin normalized the value. In
      both, IR and T2D, liver G was lower than normal, accompanied by GLUT-2, mRNA and
      protein, higher and lower, respectively, than in N; amylin normalized G in both
      groups, without changes in GLUT-2, except for an mRNA increase in T2D. In IR and
      T2D, muscle GSa was reduced, together with respective over- and under-GLUT-4
      expression; amylin induced only a trend toward GSa normalization in both groups.
      In isolated adipocytes, GT and GLUT-4 in IR and T2D were lower and higher,
      respectively, than in N; after amylin, not only GT was normalized in both groups
      but also the response to insulin was much more pronounced, including that in N,
      without major changes in GLUT-4. This suggests that the beneficial effect of
      amylin in states running with altered glucose homeostasis could occur by
      partially acting on the hexose metabolism of the liver and mainly on that of the
      adipose tissue.

PMID- 21939705
TI  - Characterization of the kallikrein-kinin system during the bovine ovulation
      process.
AB  - The kallikrein-kinin system (KKS) has been described as an important mediator of
      physiologic processes. Kallikreins use kininogen (KNG) as substrate to generate
      bradykinin, the main active peptide of the KKS that acts through two types of
      receptors, the B(1)R and the B(2)R. The goal of this study was to characterize
      some components of the KKS in different compartments of the ovary during the
      bovine ovulation process. The KNG, B(1)R and B(2)R mRNA expression patterns were
      assessed in theca and granulosa cells, as well as the bradykinin concentration
      and kallikrein-like activity in follicular fluid of bovine periovulatory
      follicles. To obtain a periovulatory follicle (>=12 mm), twenty-seven cows were
      submitted to estrus synchronization protocol and ovariectomized by colpotomy at
      0, 3, 6, 12 or 24h after a GnRH-analog injection (gonadorelin; 100 MUg, IM).
      Follicular fluid was aspirated for enzymatic assays while granulosa and theca
      cells were harvested for mRNA analysis. The mRNA expressions in follicular cells
      were evaluated by real-time RT-PCR and data representation related to the
      cyclophilin housekeeping gene. The bradykinin concentration and kallikrein-like
      activity were measured in follicular fluid by enzymatic immunoassay and selective
      substrate cleavage, respectively. The B(2)R expression in theca cells and B(1)R
      expression in theca and granulosa cells showed different profiles during the
      periovulatory period (P<0.05). The bradykinin concentration and kallikrein-like
      activity in the follicular fluid were different (P<0.05) due to the time during
      the ovulation process. KNG mRNA expression was similar for both follicular cell
      types (P>0.05). Taken together, these results provide an important
      characterization of the presence and possible KKS regulation during the bovine
      ovulation.

PMID- 21939706
TI  - Detailed analysis of inflammatory and neuromodulatory cytokine secretion from
      human NT2 astrocytes using multiplex bead array.
AB  - Astrocytes are a very important cell type in the brain fulfilling roles in both
      neuroimmunology and neurotransmission. We have conducted the most comprehensive
      analysis of secreted cytokines conducted to date (astrocytes of any source) to
      determine whether astrocytes derived from the human Ntera2 (NT2) cell-line are a
      good model of human primary astrocytes. We have compared the secretion of
      cytokines from NT2 astrocytes with those produced in astrocyte enriched human
      brain cultures and additional cytokines implicated in brain injury or known to be
      expressed in the human brain. The concentration of cytokines was measured in
      astrocyte conditioned media using multiplex bead array (MBA), where 18 cytokines
      were measured simultaneously. Resting NT2 astrocytes produced low levels (~1-30
      pg/ml) of MIP1alpha, IL-6 and GM-CSF and higher levels of MCP-1, IP-10 and IL-8
      (1-11 ng/ml) under non-inflammatory conditions. All of these in addition to IL
      1beta, TNFalpha, and IL-13, were increased by pro-inflammatory activation
      (TNFalpha or IL-1beta stimulation). In contrast, IL-2, IL-4, IL-5, IL-7, IL-10,
      IL-12, LTalpha, and IFNgamma were not detected in astrocyte conditioned media
      under any of the culture conditions tested. NT2 astrocytes were unresponsive to
      IL-2 and the adenyl cyclase agonist, forskolin. Interestingly, IFNgamma
      stimulation selectively increased IP-10 secretion only. As astrocytes stimulated
      with IL-1beta or TNFalpha produced several chemokines in the ng/ml range, we next
      assessed the chemoattractant properties of these cells. Conditioned media from
      TNFalpha-stimulated astrocytes significantly chemoattracted leukocytes from human
      blood. This study provides the most comprehensive analysis of cytokine production
      by human astrocytes thus far, and shows that NT2 astrocytes are highly responsive
      to pro-inflammatory mediators including TNFalpha and IL-1beta, producing
      cytokines and chemokines capable of attracting leukocytes from human blood. We
      conclude that in the absence of adult human primary astrocytes that NT2
      astrocytes may provide a valuable alternative to study the immunological
      behaviour of human astrocytes.

PMID- 21939707
TI  - Tacrine(2)-ferulic acid, a novel multifunctional dimer, attenuates 6
      hydroxydopamine-induced apoptosis in PC12 cells by activating Akt pathway.
AB  - Oxidative stress is closely related to the pathogenesis of neurodegenerative
      disorders such as Parkinson's disease (PD). In this study, we investigated the
      neuroprotective effect of tacrine-ferulic acid dimers linked by an
      alkylenediamine side chain (TnFA, n=2-7), a series of novel acetylcholinesterase
      inhibitors, against 6-hydroxydopamine (6-OHDA)-induced apoptosis in PC12 cells.
      Among these dimers, pre-treatment of tacrine(2)-ferulic acid (T2FA, 3-30 MUM)
      attenuated 6-OHDA-induced apoptosis in a concentration-dependent manner. The
      activations of glycogen synthase kinase 3beta (GSK3beta) and extracellular signal
      regulated kinase (ERK) were observed after the treatment of 6-OHDA. Both SB415286
      (an inhibitor of GSK3beta) and PD98059 (an inhibitor of ERK kinase) reduced the
      neurotoxicity induced by 6-OHDA, indicating that GSK3beta and ERK are involved in
      6-OHDA-induced apoptosis. T2FA was able to inhibit the activation of GSK3beta,
      but not ERK, in an Akt-dependent manner. Furthermore, LY294002, a
      phosphoinositide 3-kinase inhibitor, abolished the neuroprotective effect of
      T2FA. Collectively, these results suggest that T2FA prevents 6-OHDA-induced
      apoptosis possibly by activating the Akt pathway in PC12 cells.

PMID- 21939708
TI  - Intranasal Sendai viral vector vaccination is more immunogenic than intramuscular
      under pre-existing anti-vector antibodies.
AB  - Viral vectors are promising vaccine tools for eliciting potent cellular immune
      responses. Pre-existing anti-vector antibodies, however, can be an obstacle to
      their clinical use in humans. We previously developed a Sendai virus (SeV) vector
      vaccine and showed the potential of this vector for efficient CD8(+) T-cell
      induction in macaques. Here, we investigated the immunogenicity of SeV vector
      vaccination in the presence of anti-SeV antibodies. We compared antigen-specific
      CD8(+) T-cell responses after intranasal or intramuscular immunization with a
      lower dose (one-tenth of that in our previous studies) of SeV vector expressing
      simian immunodeficiency virus Gag antigen (SeV-Gag) between naive and pre-SeV
      infected cynomolgus macaques. Intranasal SeV-Gag immunization efficiently
      elicited Gag-specific CD8(+) T-cell responses not only in naive but also in pre
      SeV-infected animals. In contrast, intramuscular SeV-Gag immunization induced Gag
      specific CD8(+) T-cell responses efficiently in naive but not in pre-SeV-infected
      animals. These results indicate that both intranasal and intramuscular SeV
      administrations are equivalently immunogenic in the absence of anti-SeV
      antibodies, whereas intranasal SeV vaccination is more immunogenic than
      intramuscular in the presence of anti-SeV antibodies. It is inferred from a
      recent report investigating the prevalence of anti-SeV antibodies in humans that
      SeV-specific neutralizing titers in more than 70% of people are no more than
      those at the SeV-Gag vaccination in pre-SeV-infected macaques in the present
      study. Taken together, this study implies the potential of intranasal SeV vector
      vaccination to induce CD8(+) T-cell responses even in humans, suggesting a
      rationale for proceeding to a vaccine clinical trial using this vector.

PMID- 21939709
TI  - Age-related changes in durability and function of vaccine-elicited influenza
      specific CD4(+) T-cell responses.
AB  - The major antigenic component of licensed influenza vaccines, hemagglutinin (HA),
      elicits predominantly type-specific antibody responses, thus necessitating
      frequent antigenic updates to the annual vaccine. However, accumulating evidence
      suggests that influenza vaccines can also induce significant cross-reactive T
      cell responses to highly divergent, heterosubtypic HA antigens not included in
      the vaccine. Influenza vaccines are less effective among the elderly and studies
      that characterize cross-reactive T-cell immunity in this vulnerable population
      are much needed. Here, we systematically compare the ex vivo frequency, cytokine
      profile and phenotype of vaccine-elicited HA-specific T-cell responses among a
      cohort of young (18-49 years old) and elderly (>=70 years old) vaccinees, as well
      as the maturation and activation phenotype of total CD4(+) and CD8(+) T-cells.
      IFN-gamma production after in vitro expansion and HA-specific Ab titers were also
      determined. We find that vaccine-elicited ex vivo frequencies of CD4(+) T-cells
      elicited by vaccination reactive to any given homo- or heterosubtypic Ag were
      comparable across the two age groups. While, no differences were observed between
      age groups in the phenotype of Ag-specific or total CD4(+) T-cells, PBMC from
      young adults were superior at producing IFN-gamma after short-term Ag-specific
      culture. Significantly, while vaccine-elicited T-cell responses were durable
      among the younger vaccinees, they were short-lived among the elderly. These
      results have important ramifications for our understanding of vaccine-induced
      changes in the magnitude and functionality of HA-specific CD4(+) T-cells, as well
      as age-related alterations in response kinetics.

PMID- 21939710
TI  - Genetic polymorphisms in host antiviral genes: associations with humoral and
      cellular immunity to measles vaccine.
AB  - Host antiviral genes are important regulators of antiviral immunity and plausible
      genetic determinants of immune response heterogeneity after vaccination. We
      genotyped and analyzed 307 common candidate tagSNPs from 12 antiviral genes in a
      cohort of 745 schoolchildren immunized with two doses of measles-mumps-rubella
      (MMR) vaccine. Associations between SNPs/haplotypes and measles virus-specific
      immune outcomes were assessed using linear regression methodologies in Caucasians
      and African-Americans. Genetic variants within the DDX58/RIG-I gene, including a
      coding polymorphism (rs3205166/Val800Val), were associated as single-SNPs
      (p<=0.017; although these SNPs did not remain significant after correction for
      false discovery rate/FDR) and in haplotype-level analysis, with measles-specific
      antibody variations in Caucasians (haplotype allele p-value=0.021; haplotype
      global p-value=0.076). Four DDX58 polymorphisms, in high LD, demonstrated also
      associations (after correction for FDR) with variations in both measles-specific
      IFN-gamma and IL-2 secretion in Caucasians (p<=0.001, q=0.193). Two intronic OAS1
      polymorphisms, including the functional OAS1 SNP rs10774671 (p=0.003),
      demonstrated evidence of association with a significant allele-dose-related
      increase in neutralizing antibody levels in African-Americans. Genotype and
      haplotype-level associations demonstrated the role of ADAR genetic variants,
      including a non-synonymous SNP (rs2229857/Arg384Lys; p=0.01), in regulating
      measles virus-specific IFN-gamma Elispot responses in Caucasians (haplotype
      global p-value=0.017). After correction for FDR, 15 single-SNP associations (11
      SNPs in Caucasians and 4 SNPs in African-Americans) still remained significant at
      the q-value<0.20. In conclusion, our findings strongly point to genetic
      variants/genes, involved in antiviral sensing and antiviral control, as critical
      determinants, differentially modulating the adaptive immune responses to live
      attenuated measles vaccine in Caucasians and African-Americans.

PMID- 21939711
TI  - Adolescents' awareness of HPV infections and attitudes towards HPV vaccination 3
      years following the introduction of the HPV vaccine in Hungary.
AB  - Hungary takes the fourth place regarding the incidence and the fifth regarding
      the mortality of cervical cancer among the member countries of the European
      Union, with 500 deaths due to this preventable illness and nearly 1200 new cases
      diagnosed every year. Although the vaccines have been available for 3 years, the
      estimated rate of the female population vaccinated against HPV is approximately
      10% in the 12-26-year-age cohort. The aim of this study was to determine factors
      and motivations affecting the uptake of HPV vaccination among Hungarian
      adolescents. Examining the effects of some possible sociodemographic predictors
      (age and gender) and the exposure to health information on HPV vaccine
      acceptability were also focused on, as well as assessing the most trusted sources
      of information about sexually transmitted diseases (STDs). A nationwide anonymous
      questionnaire survey with a sample of 1769 students attending public primary or
      secondary schools was organised by the authors in 16 Hungarian cities and towns.
      Data were analysed using the Statistical Package for the Social Sciences (SPSS).
      Adolescents' awareness of HPV was relatively low. Only 35% of the participants
      reported they had heard about HPV prior to the survey. Almost 70% of the
      potentially affected study population had not heard about the vaccine previously.
      Every fourth student did not believe that vaccination against HPV can prevent
      cervical cancer. If the vaccination was available free of charge, almost 80% of
      respondents would request it, but in case they had to pay for it, this number
      would significantly decrease. Significantly better knowledge and also more
      positive attitudes towards HPV vaccination was found in relation to the number of
      information sources. The majority of respondents (62-83%) were open for further
      information about STDs. The main trusted mediators were school-health services
      (61.3%), education on health at school (49.2%), health professionals (42.2%) and
      electronic media (24.6%). Since Hungarian adolescent students expect guidance
      about STDs principally from school health education, an urgent need for well
      designed, HPV-focused educational programmes emerges. Launching such programmes
      would be especially important for the adolescent population to increase their
      awareness of the risks associated with HPV infection thus reducing the high
      incidence of cervical cancer in Hungary in the future.

PMID- 21939712
TI  - Neutralization of non-vaccine human papillomavirus pseudoviruses from the A7 and
      A9 species groups by bivalent HPV vaccine sera.
AB  - The majority of cervical cancers are associated with infection by one or more
      Human Papillomavirus (HPV) types from just two distinct Alpha-Papillomavirus
      species groups, A7 and A9. The extent to which the current HPV16/18 vaccines will
      protect against other genetically related HPV types is of interest to inform
      vaccine implementation, cervical disease surveillance and the development of
      second generation HPV vaccines. The aim of this study was to determine the
      frequency and titer of neutralizing antibodies against a range of A7 (18, 39, 45,
      59, 68) and A9 (16, 31, 33, 35, 52, 58) HPV types using sera from individuals
      immunized with the bivalent HPV vaccine within the school-based, UK national HPV
      immunization programme. Serum samples were collected from 69 girls aged 13-14
      years, a median 5.9 months (inter-quartile range, IQR, 5.7-6.0) after their third
      vaccine dose. Cross-neutralizing antibodies against HPV31, HPV33, HPV35 and HPV45
      were common and strongly associated with the titer for the related vaccine-type,
      but were considerably lower (<1%) than their related vaccine type-specific
      response. The low prevalence of these HPV types in the population and the ages
      within the study cohort suggest these responses are due to vaccination. It is
      unclear whether such low levels of neutralizing antibodies would be sufficient to
      protect at the site of infection in the absence of other immune effectors but the
      coincidence with HPV types reported from efficacy studies is intriguing. The
      utility of neutralizing antibodies as surrogate markers of protection remains to
      be determined.

PMID- 21939713
TI  - The recombinant gut-associated M17 leucine aminopeptidase in combination with
      different adjuvants confers a high level of protection against Fasciola hepatica
      infection in sheep.
AB  - Fasciola hepatica M17 leucine aminopeptidase (FhLAP) is thought to play a role in
      catabolizing peptides generated by the concerted activity of gut-associated
      endopeptidases on host polypeptides, thus releasing amino acids to be used in
      protein anabolism. In this study, a recombinant functional form of this homo
      hexameric metallopeptidase produced in Escherichia coli was used in combination
      with adjuvants of different types in a vaccination trial in Corriedale sheep
      against experimental challenge with F. hepatica metacercariae. The experimental
      assay consisted of 6 groups of 10 animals; 5 of the groups (1-5) were
      subcutaneously inoculated at weeks 0 and 4 with 100 MUg of rFhLAP mixed with
      Freund's complete plus incomplete adjuvant (group 1), Alum (group 2), Adyuvac 50
      (group 3), DEAE-D (group 4) and Ribi (group 5); the adjuvant control group (group
      6) received Freund's adjuvant. Two weeks after the booster, the sheep were orally
      challenged with 200 metacercariae. Immunization with rFhLAP induced significant
      reduction in fluke burdens in all vaccinated groups: 83.8% in the Freund's group,
      86.7% in the Alum group, 74.4% in the Adyuvac 50 group, 49.8% in the Ribi group
      and 49.5% in the DEAE-D group compared to the adjuvant control group.
      Morphometric analysis of recovered liver flukes showed no significant size
      modifications in the different vaccination groups. All vaccine preparations
      elicited specific IgG, IgG1 and IgG2 responses. This study shows that a liver
      fluke vaccine based on rFhLAP combined with different adjuvants significantly
      reduced worm burden in a ruminant species that was high in animals that received
      the enzyme along with the commercially approved adjuvants Alum and Adyuvac 50.

PMID- 21939714
TI  - Comparative evaluation of the antibody in lymphocyte supernatant (ALS) and enzyme
      linked immunospot (ELISPOT) assays for measuring mucosal immune responses to
      Shigella antigens.
AB  - Accurately assessing mucosal immune responses to candidate vaccines remains a
      technical challenge. ELISPOT is widely used as a surrogate of mucosal immune
      response by directly enumerating circulating antibody secreting cells (ASCs),
      while antibody in lymphocyte supernatant (ALS) titers the total amount of
      antibody secreted by ASC ex vivo using ELISA. ALS is more practical than ELISPOT
      because the ASC supernatant is frozen for ELISA that can be conducted at any
      time, with any antigen, and in any laboratory. We compared IgA and IgG responses
      to serotype-specific Shigella LPS using ELISPOT and ALS in subjects following
      vaccination or infection with Shigella. ALS results correlated well with ELISPOT
      results, and the ALS method was both sensitive and specific for the detection of
      antibody responses against Shigella LPS. Based on these observations, the ALS
      assay is a practical and flexible alternative to ELISPOT for measuring mucosal
      IgA responses to Shigella LPS antigen.

PMID- 21939715
TI  - Increased survival time in mice vaccinated with a branched lysine multiple
      antigenic peptide containing B- and T-cell epitopes from T. gondii antigens.
AB  - To develop a multiple antigenic peptide (MAP) vaccine against toxoplasmosis, tri
      epitope MAP constructs were made in dimeric fashion. The constructs included one
      B-cell and two T-cell epitopes derived from Toxoplasma gondii antigens (SAG1,
      GRA4 and GRA1) situated in tandem through the GGG spacer sequence, with the
      latter positioned adjacent to a polylysine core. Immunization of BALB/c and
      Kunming mice with the MAP construct in Freund's adjuvant induced not only humoral
      immunes response but cellular responses. These responses were accompanied by
      significant levels of splenocyte proliferation and interferon gamma (IFN-gamma)
      in vitro. After lethal challenge, vaccinated mice had increased survival time in
      comparison to unvaccinated controls. Our data demonstrate that a MAP construct
      could trigger strong humoral and cellular responses against T. gondii, and that
      this MAP is a vaccine candidate worth further development.

PMID- 21939716
TI  - Impact of Vi vaccination on spatial patterns of typhoid fever in the slums of
      Kolkata, India.
AB  - A mass typhoid Vi vaccination campaign was carried out among approximately 60,000
      slum residents of Kolkata, India. This study evaluated the impact of the campaign
      on spatial patterns of typhoid fever. Eighty contiguous residential groups of
      households in the study area were randomized to receive either a single dose of
      the Vi polysaccharide vaccine or a single dose of the inactivated hepatitis A
      vaccine as the control agent. Persons aged two years and older were eligible to
      receive the vaccine. Vaccine protection against typhoid fever was monitored for
      two years after vaccination at both outpatient and inpatient facilities serving
      the study population. Geographic analytic and mapping tools were used in the
      analysis. Spatial randomness of the disease was observed during the pre
      vaccination period, which turned into a significant pattern after vaccination.
      The high-risk areas for typhoid were observed in the area dominated by the
      control clusters, and the low-risk areas were in the area dominated by the Vi
      clusters. Furthermore, the control clusters surrounded by the Vi clusters were
      low risk for typhoid fever. The results demonstrated the ability of mass
      vaccination to change the spatial patterns of disease through the creation of
      spatial barriers to transmission of the disease. Understanding and mapping the
      disease risk could be useful for designing a community-based vaccination strategy
      to control disease.

PMID- 21939717
TI  - Immunogenicity of novel nanoparticle-coated MSP-1 C-terminus malaria DNA vaccine
      using different routes of administration.
AB  - An important aspect in optimizing DNA vaccination is antigen delivery to the site
      of action. In this way, any alternative delivery system having higher
      transfection efficiency and eventual superior antibody production needs to be
      further explored. The novel nanoparticle, pDNA/PEI/gamma-PGA complex, is one of a
      promising delivery system, which is taken up by cells and is shown to have high
      transfection efficiency. The immunostimulatory effect of this novel nanoparticle
      (NP) coated plasmid encoding Plasmodium yoelii MSP1-C-terminus was examined.
      Groups of C57BL/6 mice were immunized either with NP-coated MSP-1 plasmid, naked
      plasmid or NP-coated blank plasmid, by three different routes of administration;
      intravenous (i.v.), intraperitoneal (i.p.) and subcutaneous (s.c). Mice were
      primed and boosted twice at 3-week intervals, then challenged 2 weeks after; and
      100%, 100% and 50% mean of survival was observed in immunized mice with coated
      DNA vaccine by i.p., i.v. and s.c., respectively. Coated DNA vaccine showed
      significant immunogenicity and elicited protective levels of antigen specific IgG
      and its subclass antibody, an increased proportion of CD4(+) and CD8(+) T cells
      and INF-gamma and IL-12 levels in the serum and cultured splenocyte supernatant,
      as well as INF-gamma producing cells in the spleen. We demonstrate that, NP
      coated MSP-1 DNA-based vaccine confers protection against lethal P. yoelii
      challenge in murine model across the various route of administration and may
      therefore, be considered a promising delivery system for vaccination.

PMID- 21939718
TI  - Development and characterization of chitosan coated poly-(E-caprolactone)
      nanoparticulate system for effective immunization against influenza.
AB  - In this study surface coated poly-(E-caprolactone) (PCL) nanoparticles with
      chitosan (CS) were developed as a carrier system for nasal immunization using
      recombinant Influenza A virus (A/California/07/2009) H1N1 hemagglutinin (HA)
      protein, for the induction of humoral, cellular and mucosal immunity. CS coated
      PCL (CS-PCL) nanoparticles were characterized in vitro for their percent yield,
      size, shape, entrapment efficiency, loading capacity and zeta potential. The in
      vitro release and antigen integrity were also evaluated. Particles were prepared
      by an emulsion-diffusion-solvent evaporation method. The coated cationic
      nanoparticles of average size 125.64+/-6.51 nm with a narrow size distribution
      (pdi: 0.185+/-0.032) and a positive surface charge (+22.88 mV) were obtained. HA
      antigen was efficiently entrapped in CS-PCL nanoparticles (entrapment efficiency
      74.84+/-4.51%, loading capacity 14+/-2% (w/w)). The molecular weight and
      antigenicity of the entrapped HA was maintained as shown by polyacrylamide gel
      electrophoresis and Western blotting, respectively. In vitro release study of
      antigen showed that about 66.47% of entrapped antigen was released within 63
      days. The immune-stimulating activity was studied by measuring hemagglutination
      inhibition (HAI) titer, IgG, IgG1 and IgG2a titer, secretory IgA level in nasal
      and lung lavage (mucosal secretions) following nasal administration of modified
      CS-PCL nanoparticles in Balb/c mice and compared with soluble HA antigen
      administered intramuscular (IM) and with PCL (uncoated) nanoparticles
      administered intranasal (IN). The numbers of IFN-gamma or IL-4 secreting cells in
      spleen homogenates were also measured 21 day after third immunization. Single IN
      or IM immunization with antigen-loaded CS-PCL nanoparticles resulted in strong
      HAI and total IgG responses. These responses were higher than those achieved
      after booster IM administration of the subunit antigen, whereas the IgG1/IgG2a
      profile did not change substantially. The IN administered antigen-CS-PCL
      nanoparticles induced higher immune responses compared to the other IN antigen
      formulations, and these responses were enhanced by IN booster vaccinations.
      Moreover, IM administered soluble HA antigen did not elicit s-IgA in mucosal
      secretions as it was induced and measured in the case of nasal administration of
      CS-PCL nanoparticles. In contrast to IM administered antigen CS-PCL nanoparticles
      induced a balanced Th1 and Th2 response. CS-PCL nanoparticles (cationic
      nanoparticles) thus produced humoral (both systemic and mucosal) and cellular
      immune responses upon nasal administration. These findings demonstrate high
      potential of CS-PCL nanoparticles for their use as a carrier adjuvant for nasal
      administered influenza antigens.

PMID- 21939719
TI  - Rapid and accurate determination of the potency of varicella vaccine by
      quantitative polymerase chain reaction.
AB  - The potency of varicella vaccines is currently determined by a plaque assay
      technique, which usually takes seven days and is laborious and has considerable
      inter- and intra-assay variability. Here, we report a new potency assay for
      varicella vaccine based on quantitative polymerase chain reaction in conjunction
      with a much more efficient virus infection step. Potency results can be obtained
      within 24h of infection and demonstrates acceptable accuracy and reproducibility
      when compared with the plaque assay, which relies on manual counting of plaques
      formed one week after viral infection. Using multiple vaccine lots from 7
      manufacturers, we found no significant difference in infectivity determined
      between the new assay and plaque assay. The optimized conditions for viral
      infection and polymerase chain reaction are of significant value for the potency
      determination of the vaccine due to its rapidity, accuracy and the high
      throughput capacity of the assay.

PMID- 21939720
TI  - Viral interference induced by live attenuated virus vaccine (OPV) can prevent
      otitis media.
AB  - BACKGROUND: The goal of this study was to evaluate whether a live attenuated
      poliovirus vaccine (OPV) has clinically relevant interfering effect with non
      polio infections causing otitis media in young children. METHODS: Open trial in
      which the intervention group (64 children) received OPV at the age of 2, 3, 6 and
      12 months. The control group (250 children) received IPV (inactivated polio
      vaccine) at the age of 6 and 12 months. Clinical symptoms were recorded by a
      questionnaire at the age of 3, 6, 12, 18 and 24 months. RESULTS: Otitis media
      episodes were less frequent in the OPV than in the control group. A significant
      difference was seen at the age of 6-18 months (IRR=0.76 [95% CI 0.59-0.94],
      P=0.011) and was particularly clear among children, who attended daycare (IRR
      0.37 [95% CI 0.19-0.71], P=0.003). CONCLUSIONS: OPV provides some protection
      against otitis media. This effect may be mediated by viral interference with non
      polio viruses.

PMID- 21939721
TI  - Population-based incidence of herpes zoster after introduction of a publicly
      funded varicella vaccination program.
AB  - BACKGROUND: Past varicella infection (chicken pox) may reactivate into herpes
      zoster (shingles). Varicella vaccination leads to a reduction in cases of
      varicella that may in turn increase herpes zoster rates due to reduction in the
      immune boosting effect of exposure to varicella zoster virus against varicella
      reactivation. We assessed the impact of childhood varicella vaccination in
      Ontario, Canada on zoster incidence and healthcare visits, and established
      baseline zoster rates prior to zoster vaccine introduction. METHODS: We used
      population-based, administrative databases to identify zoster incidence and
      healthcare use from April 1992 to March 2010. RESULTS: After routine varicella
      vaccination, zoster incidence rates decreased 29% for children aged 0-9 and
      changed minimally for other ages. Age-standardized rates of hospitalizations
      during the study period declined by 53%, while outpatient rates declined by 9%.
      The annual zoster incidence for those 60 or older was 740 per 100,000.
      CONCLUSIONS: In the early post-varicella vaccination period, incidence rates of
      medically attended herpes zoster did not increase for the overall population and
      decreased moderately for children 9 years and younger, the age group targeted for
      varicella vaccination.

PMID- 21939722
TI  - Planning for influenza vaccination in health care workers: an Intervention
      Mapping approach.
AB  - Influenza vaccination uptake by health care workers (HCWs) decreases the
      transmission of influenza to vulnerable patients and prevents influenza-related
      absenteeism. Vaccination is effective, easy, and generally without serious side
      effects. However, vaccination rates of HCWs are too low. This paper's objective
      is to apply Intervention Mapping (IM), a planning process for the systematic
      theory- and evidence-based development of health promotion interventions, to the
      development of voluntary educational interventions to promote influenza
      vaccination in HCWs. IM consists of the following six steps: needs assessment,
      program objectives, methods and applications, program development, planning for
      program implementation, and planning for program evaluation. Examples are
      provided to illustrate the activities associated with these steps. It is
      concluded that applying IM in the (influenza) vaccination field may help the
      development of effective behavior change interventions.

PMID- 21939723
TI  - Mucosal antibodies induced by tandem repeat of 2F5 epitope block transcytosis of
      HIV-1.
AB  - Induction of mucosal antibodies to prevent HIV infection is an important strategy
      for the HIV-1 prophylaxis. Here we report an epitope-vaccine based antigen that
      was able to elicit mucosal antibodies capable of blocking HIV-1 transcytosis.
      Because the ELDKWA epitope of neutralizing antibody 2F5 plays a crucial role in
      transcytosis, a series of immunogens that contain tandem copies of ELDKWA were
      prepared. Mice were immunized with these immunogens intranasally, and received
      intraperitoneal+intranasal boosters. The immunogens that contained more ELDKWA
      epitopes elicited higher level of mucosal ELDKWA-epitope specific IgAs and
      systemic IgGs. Although the antisera from the immunized mice exhibited mild
      neutralizing potency to HIV-1 isolates HXB2 and JRFL, the affinity purified
      mucosal ELDKWA-epitope specific antibodies could block the transcytosis of cell
      free CNE3 (a primary isolate of subtype CRF01_AE) in human tight epithelial
      models.

PMID- 21939724
TI  - Effectiveness of 7-valent pneumococcal conjugate vaccine in the prevention of
      invasive pneumococcal disease in children aged 7-59 months. A matched case
      control study.
AB  - The aim of this study was to evaluate the effectiveness of the administration of
      the 7-valent pneumococcal conjugate vaccine in a region with an intermediate
      vaccination coverage. A matched case-control study was carried out in children
      aged 7-59 months with invasive pneumococcal disease (IPD) admitted to two
      university hospitals in Catalonia. Three controls matched for hospital, age, sex,
      date of hospitalization and underlying disease were selected for each case.
      Information on the vaccination status of cases and controls was obtained from the
      vaccination card, the child's health card, the hospital medical record or the
      vaccination register of the primary healthcare center where the child was
      attended for non-severe conditions. A conditional logistic regression analysis
      was made to control for the effect of possible confounding variables. The
      adjusted vaccination effectiveness of the complete vaccination schedule (3 doses
      at 2, 4 and 6 months and a fourth dose at 15 months, 2 doses at least two months
      apart in children aged 12-23 months or a single dose in children aged >24 months)
      in preventing IPD caused by vaccine serotypes was 93.7% (95% CI 51.8-99.2). It
      was not effective in preventing cases caused by non-vaccine serotypes. The
      results of this study carried out in a population with intermediate vaccination
      coverage confirm those of other observational studies showing high levels of
      effectiveness of routine 7-valent pneumococcal conjugate vaccination.

PMID- 21939725
TI  - Therapeutic effect of paroxetine on stress-induced gastric lesions in mice.
AB  - Compared to the well-known anti-ulcerogenic properties of tricyclic
      antidepressants, the impact of selective serotonin reuptake inhibitors (SSRIs) on
      gastric mucosa is less clear. Human clinical trials have shown that SSRIs and non
      steroidal anti-inflammatory drugs (NSAIDs) act synergistically and promote
      stomach ulcer formation and upper gastrointestinal tract bleeding. Acute SSRI
      treatment confers an additional risk for the formation of NSAID-induced gastric
      ulcers through increase in gastric acid secretion. Stress, which is often
      experienced by depressed patients, also deteriorates the gastric environment.
      Thus the potential for exacerbating stress-induced gastric lesions must be
      considered before prescribing SSRIs. Therefore, we evaluated the effects of
      paroxetine by using a water-immersion stress-induced stomach ulcer model of mice,
      by examining single vs. repeated paroxetine treatments for 8 and 22 days before
      stress induction. Repeated administration of paroxetine significantly decreased
      the area of stress-induced stomach lesions. Although stress significantly
      increased the serum corticosterone concentrations, the levels were not affected
      by the 8-day paroxetine treatment. We confirmed the anxiolytic and antidepressive
      effects of 8-day paroxetine treatment at 1 and 5 days after stress induction by
      using the elevated plus-maze and tail-suspension tests. We concluded that
      repeated paroxetine treatment significantly attenuates the stress-induced
      ulcerogenic process in the stomach.

PMID- 21939726
TI  - Melatonin improves 3-nitropropionic acid induced behavioral alterations and
      neurotrophic factors levels.
AB  - OBJECTIVE: This study sought to determine whether melatonin causes changes in
      neurotrophic factors and it protects against the mycotoxin 3-nitropropionic acid
      (3-NP) in brain tissue. METHODS: Rats were given 3-NP over four consecutive days
      (20 mg/kg BW), while melatonin was administered over 21 days (1 mg/kg/BW),
      starting after the last injection of 3-NP. RESULTS: Rats treated with 3-NP
      displayed significant changes in neurotrophic factor (BDNF and GDNF) levels,
      together with alterations in behavior; they also displayed extensive oxidative
      stress and a massive neuronal damage. CONCLUSIONS: Melatonin improved behavioral
      alterations, reduced oxidative damage, lowered neurotrophic factor levels and
      neuronal loss in 3-NP-treated rats. These results suggest that melatonin exerts a
      neuroprotective action.

PMID- 21939727
TI  - Subchronic oral toxicity and cardiovascular safety pharmacology studies of
      resveratrol, a naturally occurring polyphenol with cancer preventive activity.
AB  - To characterize the subchronic oral toxicity of resveratrol, CD rats received
      daily gavage doses of 0, 200, 400, or 1000 mg resveratrol/kg/day, and beagle dogs
      received daily capsule doses of 0, 200, 600, or 1200 mg resveratrol/kg/day for 90
      days. Resveratrol induced only minimal toxicity, consisting of dose-related
      reductions in body weight gain in female rats and both sexes of dogs, and a
      statistically significant increase in bilirubin levels in rats at the 1000
      mg/kg/day dose. Clinical observations, hematology, ophthalmology, neurotoxicity
      evaluations (functional observational batteries), organ weights, and gross
      pathology provided no biologically significant evidence of resveratrol toxicity
      in either species. In rats, the high dose of resveratrol reduced the incidence of
      cardiomyopathy; no other microscopic changes were seen. Histopathologic changes
      in dogs were limited to minimal inflammatory infiltrates in the kidney and
      urinary bladder, which were not considered toxicologically significant. A
      cardiovascular safety pharmacology (telemetry) study in dogs revealed no evidence
      of resveratrol toxicity. Based on body weight effects, the No Observed Adverse
      Effect Level (NOAEL) for resveratrol was 200mg/kg/day in rats and 600 mg/kg/day
      in dogs. The apparent cardioprotective activity of resveratrol in rats
      demonstrates that its potentially beneficial activities may extend beyond
      efficacy in cancer prevention.

PMID- 21939728
TI  - Evaluation of anti-diabetic potential of chromium(III) propionate complex in high
      fat diet fed and STZ injected rats.
AB  - The aim of this study was to examine the anti-diabetic potential of the
      chromium(III) propionate complex (CrProp) in a diabetic rat model. Male Wistar
      rats (n=28, 8-week old) were divided into 4 groups (with 7 rats each) and fed at
      libitum: the control diet (AIN-93M), and high-fat diets with or without
      supplementary CrProp (10 and 50mg Crkg(-1) diet; 1 and 5 mg kg(-1) body mass per
      day) for 5 weeks, and subsequently injected with STZ to induce diabetes. Rats
      were further fed the same diets for another week until the end of the experiment.
      Blood indices and the contents of minerals (Fe, Zn, Cu and Cr) in rat tissues
      were determined by atomic absorption spectrometry. Supplementary CrProp did not
      affect blood glucose level, but significantly improved insulin sensitivity (HOMA
      IR index) and reduced serum levels of triacylglycerols, total and LDL
      cholesterols. Both supplementary dosages of CrProp (10 and 50mg Cr kg(-1) diet)
      normalized the increased liver Fe content, reduced hepatic and renal Cu levels
      and elevated renal Cr contents in diabetic rats. In conclusion, CrProp has a
      significant anti-diabetic (insulin-sensitizing and hypolipidemic) potential; thus
      it might be a candidate for a therapeutic agent in diabetes.

PMID- 21939729
TI  - Cytokines and innate inflammation in the pathogenesis of human traumatic brain
      injury.
AB  - There is an increasing recognition that following traumatic brain injury, a
      cascade of inflammatory mediators is produced, and contributes to the
      pathological consequences of central nervous system injury. This review
      summarises the key literature from pre-clinical models that underlies our
      understanding of innate inflammation following traumatic brain injury before
      focussing on the growing evidence from human studies. In addition, the underlying
      molecular mediators responsible for blood brain barrier dysfunction have been
      discussed. In particular, we have highlighted the different sampling
      methodologies available and the difficulties in interpreting human data of this
      sort. Ultimately, understanding the innate inflammatory response to traumatic
      brain injury may provide a therapeutic avenue in the treatment of central nervous
      system disease.

PMID- 21939730
TI  - Characterization of chicken secretin (SCT) and secretin receptor (SCTR) genes: a
      novel secretin-like peptide (SCT-LP) and secretin encoded in a single gene.
AB  - Secretin and the secretin receptor have been reported to play an important role
      in regulating pancreatic water and bicarbonate secretion in mammals; however,
      little is known about their expression, structure, and biological functions in
      non-mammalian vertebrates including birds. In this study, the full-length cDNAs
      encoding secretin and secretin receptor have first been cloned from duodenum of
      adult chickens. The putative chicken secretin receptor (cSCTR) is 449 amino acids
      in length and shares high sequence identity (58-63%) with its mammalian
      counterparts. Interestingly, chicken secretin cDNA encodes not only the secretin
      peptide (cSCT), but also a novel secretin-like peptide (cSCT-LP), which shares
      high amino acid identity with chicken (56%) and mammalian (48-52%) secretin.
      Using a pGL3-CRE-luciferase reporter system, we further demonstrated that both
      cSCT (EC(50): 0.31nM) and cSCT-LP (EC(50): 1.10nM), but not other structurally
      related peptides, could potently activate cSCTR expressed in CHO cells,
      suggesting that both peptides may function as potential ligands for cSCTR. Using
      RT-PCR, the expression of secretin and secretin receptor in adult chicken tissues
      was also examined. Secretin was detected to be predominantly expressed in small
      intestine, while the mRNA expression of cSCTR was restricted to several tissues
      including gastrointestinal tract, liver, testis, pancreas and several brain
      regions. Collectively, results from present study not only established a
      molecular basis to elucidate the physiological roles of SCT, SCT-LP and SCTR in
      chickens, but also provide critical insights into structural and functional
      changes of secretin and its receptor during vertebrate evolution.

PMID- 21939731
TI  - Thyroid effects of endocrine disrupting chemicals.
AB  - In recent years, many studies of thyroid-disrupting effects of environmental
      chemicals have been published. Of special concern is the exposure of pregnant
      women and infants, as thyroid disruption of the developing organism may have
      deleterious effects on neurological outcome. Chemicals may exert thyroid effects
      through a variety of mechanisms of action, and some animal experiments and in
      vitro studies have focused on elucidating the mode of action of specific chemical
      compounds. Long-term human studies on effects of environmental chemicals on
      thyroid related outcomes such as growth and development are still lacking. The
      human exposure scenario with life long exposure to a vast mixture of chemicals in
      low doses and the large physiological variation in thyroid hormone levels between
      individuals render human studies very difficult. However, there is now reasonably
      firm evidence that PCBs have thyroid-disrupting effects, and there is emerging
      evidence that also phthalates, bisphenol A, brominated flame retardants and
      perfluorinated chemicals may have thyroid disrupting properties.

PMID- 21939732
TI  - PPARG gene Pro12Ala variant contributes to the development of non-alcoholic fatty
      liver in middle-aged and older Chinese population.
AB  - Oxidative stress has been suggested to contribute to the development of non
      alcoholic fatty liver disease (NAFLD). Peroxisome proliferator-activated receptor
      gamma (PPAR-gamma) heterozygous mice and Pro12Ala (C/G) polymorphism in PPARG
      exhibited increased resistance to oxidative stress. Smoking increases the
      production of reactive oxygen species, which could accelerates oxidative stress
      under overnutrition. To explore whether the C/G polymorphism, alone or in
      combination with smoking, may promote the development of non-alcoholic fatty
      liver, a case-control study was performed in 903 Chinese subjects. Among the
      study population, 436 patients with B-mode ultrasound-proven NAFLD (318 with
      steatosis hepatis I degrees , 90 with steatosis hepatis II degrees  and 28 with
      steatosis hepatis III degrees ) and 467 controls were genotyped by using TaqMan
      allelic discrimination assays. After adjusting for confounders, the C/C genotype
      significantly associated with NAFLD (OR=1.87, 95%CI 1.13-2.85, p=0.009); smoking
      was also an independent risk factor for NAFLD (OR=1.69, 95%CI 1.18-2.43,
      p=0.025). In addition, we found possible synergistic effects, the higher risk
      group (smokers with the C/C genotype) showed 3.75 times higher risk of NAFLD than
      the low-risk group (non-smokers with C/G genotype) in a multiple logistic
      analysis after adjusting for the confounders (p<0.001), but no departure from
      additivity was found. Our results indicated that the C/C genotype and smoking
      were significant independent risk factors for NAFLD. The possible synergistic
      effects of genotype and smoking may promote the development of NAFLD by
      aggravating oxidative stress, which supports the hypothesis that oxidative stress
      contributes to the development of NAFLD.

PMID- 21939734
TI  - Transcranial sonography findings in spinocerebellar ataxia type 3 (Machado-Joseph
      disease): a cross-sectional study.
AB  - Few studies on transcranial brain sonography have been performed in hereditary
      and non-hereditary ataxias. The objective of the present study was to report
      transcranial brain sonography findings in a sample of clinically and molecularly
      proven Machado-Joseph disease patients and to compare these data against those of
      an age- and gender-matched control group. A cross-sectional study on transcranial
      brain sonography was conducted in 30 Machado-Joseph disease patients.
      Transcranial brain sonography was performed by an experienced sonographer blinded
      to the clinical, genetic, and neuroimaging data. The results were compared with
      those of a control group of 44 healthy subjects matched for age and gender. The
      sonographic findings were also correlated with clinical features and genetic data
      in Machado-Joseph disease group. A significantly higher frequency of substantia
      nigra and lenticular nucleus hyperechogenicity was found in the Machado-Joseph
      disease group compared to an age- and gender-matched healthy control group
      (p<0.001). The substantia nigra echogenic area proved to be the best predictor
      for differentiating cases from controls. Third and lateral ventricles were
      significantly larger in the Machado-Joseph disease patients than in the control
      subjects. No significant correlations were found between transcranial brain
      sonography findings and Machado-Joseph disease demographic/clinical data.
      Transcranial brain sonography findings in Machado-Joseph disease patients
      differed significantly to those in age- and gender-matched controls. Substantia
      nigra hyperechogenicity occurred frequently in Machado-Joseph disease patients
      and was found to be the best predictor for differentiating cases from controls.
      Additionally, this data describes the occurrence of brain atrophy in Machado
      Joseph disease group.

PMID- 21939735
TI  - Valproate protects the retina from endoplasmic reticulum stress-induced apoptosis
      after ischemia-reperfusion injury.
AB  - Valproate (VPA) is commonly used in the treatment of bipolar disorder and
      epilepsy. The mechanism underlying its clinical efficacy is complicated,
      including its ability to inhibit histone deacetylase (HDAC). Here, we show that
      VPA promoted endoplasmic reticulum (ER) chaperone expression and attenuated ER
      induced apoptosis after ischemia/reperfusion (I/R) injury in retina. Male Wistar
      rats were randomly divided into four groups: sham (group A), sham+VPA (group B),
      I/R+vehicle (group C), and I/R+VPA (group D). VPA was administered subcutaneously
      at 300mg/kg twice daily before insult. Morphological changes were analyzed on
      stained histological sections and flat-mounted retinas labeled by Fluoro-gold.
      Western blot analysis was used to determine protein levels of GRP78, CHOP,
      caspase-12 and acetylation of histone H3 in each group. In group C, the severe
      retinal damage was shown in histological sections, however, the damage was
      reduced by VPA in group D. Significant loss of retinal ganglion cells (RGCs) was
      observed in group C, whereas, the density of RGCs was significantly higher in
      group D at 7days post-insult. VPA increased GRP78 expression and acetylation of
      histone H3, attenuated upregulation of CHOP and activation of caspase-12 in group
      D. Our results suggest that VPA can protect ischemic retinas from ER stress
      induced apoptosis by mechanisms that may involve HDAC inhibition.

PMID- 21939737
TI  - Magnetic stimulation intensity modulates motor inhibition.
AB  - Repetitive transcranial magnetic stimulation (rTMS) is a standard tool in
      neuroscience research and therapy. Here we study one rTMS property that has not
      received adequate attention, the interaction of subthreshold intensity
      stimulation and low frequencies. We applied 1Hz rTMS over the motor cortex at
      three intensities, 40%, 80% and 100% of the resting motor threshold (rMT), and
      measured cortical excitability before and after the stimulation sessions. When
      comparing motor evoked potential (MEP) measured from the abductor pollicis brevis
      (APB) muscle before and after rTMS stimulation, we found that low intensity (40%
      MT) stimulation significantly decreased MEP magnitude, some smaller (non
      significant) inhibition was found for the 80% MT intensity and increased MEP was
      found for the high intensity (100% MT) stimulation. Our results indicate that
      when explaining the input-output relationship of motor cortex induced activation
      as an intensity-dependent function, there might be a need to split it into
      separate functions associated with separate processes mediated by different cell
      types such as interneurons, pyramidal neurons and others.

PMID- 21939733
TI  - Circadian system, sleep and endocrinology.
AB  - Levels of numerous hormones vary across the day and night. Such fluctuations are
      not only attributable to changes in sleep/wakefulness and other behaviors but
      also to a circadian timing system governed by the suprachiasmatic nucleus of the
      hypothalamus. Sleep has a strong effect on levels of some hormones such as growth
      hormone but little effect on others which are more strongly regulated by the
      circadian timing system (e.g., melatonin). Whereas the exact mechanisms through
      which sleep affects circulating hormonal levels are poorly understood, more is
      known about how the circadian timing system influences the secretion of hormones.
      The suprachiasmatic nucleus exerts its influence on hormones via neuronal and
      humoral signals but it is now also apparent that peripheral tissues contain
      circadian clock proteins, similar to those in the suprachiasmatic nucleus, that
      are also involved in hormone regulation. Under normal circumstances, behaviors
      and the circadian timing system are synchronized with an optimal phase
      relationship and consequently hormonal systems are exquisitely regulated.
      However, many individuals (e.g., shift-workers) frequently and/or chronically
      undergo circadian misalignment by desynchronizing their sleep/wake and
      fasting/feeding cycle from the circadian timing system. Recent experiments
      indicate that circadian misalignment has an adverse effect on metabolic and
      hormonal factors such as circulating glucose and insulin. Further research is
      needed to determine the underlying mechanisms that cause the negative effects
      induced by circadian misalignment. Such research could aid the development of
      novel countermeasures for circadian misalignment.

PMID- 21939736
TI  - Function of prostaglandin E2 EP receptors in the acute outcome of rodent hypoxic
      ischemic encephalopathy.
AB  - Neonatal hypoxic-ischemic encephalopathy (HIE) is a leading cause of severe and
      permanent neurologic disability after birth. The inducible cyclooxygenase COX-2,
      which along with COX-1 catalyzes the first committed step in prostaglandin (PG)
      synthesis, elicits significant brain injury in models of cerebral ischemia;
      however its downstream PG receptor pathways trigger both toxic and paradoxically
      protective effects. Here, we investigated the function of PGE(2) E-prostanoid
      (EP) receptors in the acute outcome of hypoxic-ischemic (HI) injury in the
      neonatal rat. We determined the temporal and cellular expression patterns of the
      EP1-4 receptors before and after HIE and tested whether modulation of EP1-4
      receptor function could protect against cerebral injury acutely after HIE. All
      four EP receptors were expressed in forebrain neurons and were induced in
      endothelial cells after HIE. Inhibition of EP1 signaling with the selective
      antagonist SC-51089 or co-activation of EP2-4 receptors with the agonist
      misoprostol significantly reduced HIE cerebral injury 24 h after injury. These
      receptor ligands also protected brain endothelial cells subjected to oxygen
      glucose deprivation, suggesting that activation of EP receptor signaling is
      directly cytoprotective. These data indicate that the G-protein coupled EP
      receptors may be amenable to pharmacologic targeting in the acute setting of
      neonatal HIE.

PMID- 21939739
TI  - Characterization of nuclear neurokinin 3 receptor expression in rat brain.
AB  - Ligand-induced translocation of the G-protein-coupled receptor, neurokinin 3 (NK3
      R), to the nucleus of hypothalamic neurons was reported using antibodies (ABs)
      raised against the C-terminal region of NK3-R. The current work was undertaken to
      substantiate the ability of NK3-R to enter the nucleus and identify which portion
      of the NK3-R molecule enters the nucleus. ABs directed at epitopes in the N
      terminal and second extracellular loop of the rat NK3-R molecule were used to
      evaluate western blots of whole tissue homogenates and nuclear fractions from
      multiple brain areas. Specificity of the protein bands recognized by these ABs
      was demonstrated using Chinese hamster ovary (CHO) cells transfected with rat or
      human NK3-R. Both ABs prominently recognized a diffuse protein band of ~56-65 kDa
      (56 kDa=predicted size) and distinct ~70-kDa and 95-kDa proteins in homogenates
      of multiple brain areas. The ~95-kDa protein recognized by the extracellular loop
      AB was enriched in nuclear fractions. Recognition of these proteins by ABs
      directed at different regions of the NK3-R supports their identification as NK3
      R. The size differences reflect variable glycosylation and possibly linkage to
      different cytosolic and nuclear proteins. Recognition of protein bands by both
      ABs in nuclear fractions is consistent with the full-length NK3-R entering the
      nucleus. Hypotension increased the density of the ~95-kDa band in nuclear
      fractions from the supraoptic nucleus indicating activity-induced nuclear
      translocation. Since NK3-R is widely distributed in the CNS, the presence of NK3
      R in nuclei from multiple brain regions suggests that it may broadly influence
      CNS gene expression in a ligand-dependent manner.

PMID- 21939740
TI  - Regulated expression of neuronal SIRT1 and related genes by aging and neuronal
      beta2-containing nicotinic cholinergic receptors.
AB  - Longevity genes attenuate the aging process, but their expression in the brain
      during aging remains unknown. Loss of the majority of heteromeric brain nicotinic
      acetylcholine receptors (nAChRs) results in premature brain aging, and altered
      regulation of longevity genes could be involved. Using in situ hybridization, the
      expression of SIRT1, Ku70, Nampt, p53, forkhead Box O3 (FoxO3), and mitochondria
      uncoupling protein 5 (UCP5) was determined in neocortex and hippocampus of young
      adult 3-month and middle-aged 18-month-old wild-type (WT), and age-matched mice
      lacking beta2* heteromeric nAChRs (beta2-/-). Age-related structural changes were
      detected in WT mice. In particular, cortical thickness was decreased but neuronal
      density increased, and hippocampal volume increased with age. In contrast, young
      beta2-/- mice exhibited increased cortical neuronal density, and with age,
      cortical thickness decreased more dramatically, and hippocampal volume did not
      increase. Thus, young beta2-/- mice exhibited cortical signs of aging, and aging
      was accelerated at 18 months. The longevity genes probed exhibited similar
      expression patterns in frontal brain structures, with strong expression in
      hippocampus, medial habenula (MHb), and cortex. In WT mice, age significantly
      decreased expression of all genes except SIRT1 in cortical structures, and a
      similar pattern was detected in the MHb. Genotype had no effect on expression in
      young adults in either cortex or MHb, but increased mRNA expression of SIRT1,
      Nampt, and Ku70 was detected in cortex, hippocampus, and MHb of aged beta2-/-
      mice compared with WT mice. This is the first study to determine age-related
      expression of survival genes in forebrain areas. Although, structural changes
      indicative of accelerated aging are evident in young beta2-/- mice, the data
      suggest that nAChRs do not directly regulate expression of survival genes.
      However, loss of beta2* nAChRs could result in augmented cellular stress, which
      indirectly increases expression of SIRT1, Nampt, and Ku70 as an adaptive response
      to provide protection against neurodegeneration.

PMID- 21939742
TI  - Neural-activity mapping of memory-based dominance in the crow: neural networks
      integrating individual discrimination and social behaviour control.
AB  - Large-billed crows (Corvus macrorhynchos), highly social birds, form stable
      dominance relationships based on the memory of win/loss outcomes of first
      encounters and on individual discrimination. This socio-cognitive behaviour
      predicts the existence of neural mechanisms for integration of social behaviour
      control and individual discrimination. This study aimed to elucidate the neural
      substrates of memory-based dominance in crows. First, the formation of dominance
      relationships was confirmed between males in a dyadic encounter paradigm. Next,
      we examined whether neural activities in 22 focal nuclei of pallium and
      subpallium were correlated with social behaviour and stimulus familiarity after
      exposure to dominant/subordinate familiar individuals and unfamiliar
      conspecifics. Neural activity was determined by measuring expression level of the
      immediate-early-gene (IEG) protein Zenk. Crows displayed aggressive and/or
      submissive behaviour to opponents less frequently but more discriminatively in
      subsequent encounters, suggesting stable dominance based on memory, including
      win/loss outcomes of the first encounters and individual discrimination. Neural
      correlates of aggressive and submissive behaviour were found in limbic subpallium
      including septum, bed nucleus of the striae terminalis (BST), and nucleus taeniae
      of amygdala (TnA), but also those to familiarity factor in BST and TnA.
      Contrastingly, correlates of social behaviour were little in pallium and those of
      familiarity with exposed individuals were identified in hippocampus, medial meso
      /nidopallium, and ventro-caudal nidopallium. Given the anatomical connection and
      neural response patterns of the focal nuclei, neural networks connecting pallium
      and limbic subpallium via hippocampus could be involved in the integration of
      individual discrimination and social behaviour control in memory-based dominance
      in the crow.

PMID- 21939741
TI  - Chronic, noninvasive glucocorticoid administration suppresses limbic
      endocannabinoid signaling in mice.
AB  - Limbic endocannabinoid signaling is known to be sensitive to chronic stress;
      however, studies investigating the impact of prolonged exposure to glucocorticoid
      hormones have been limited by the concurrent exposure to the stress of daily
      injections. The present study was designed to examine the effects of a
      noninvasive approach to alter plasma corticosterone (CORT) on the endocannabinoid
      system. More precisely, we explored the effects of a 4-week exposure to CORT
      dissolved in the drinking water of mice (100 MUg/ml) and measured cannabinoid
      CB(1) receptor binding, endocannabinoid content, activity of the endocannabinoid
      degrading enzyme fatty acid amide hydrolase (FAAH), and mRNA expression of both
      the CB(1) receptor and FAAH in both the hippocampus and amygdala. Our data
      demonstrate that CORT decreases CB(1) receptor binding site density in both the
      hippocampus and amygdala and also reduced anandamide (AEA) content and increased
      FAAH activity within both structures. These changes in both CB(1) receptor
      binding and FAAH activity were not accompanied by changes in mRNA expression of
      either the CB(1) receptor or FAAH in either brain region. Interestingly, our CORT
      delivery regimen significantly increased 2-AG concentrations within the
      hippocampus, but not the amygdala. Collectively, these data demonstrate that the
      confounder of injection stress is sufficient to conceal the ability of protracted
      exposure to glucocorticoids to reduce CB(1) receptor density and augment AEA
      metabolism within limbic structures.

PMID- 21939738
TI  - Dopamine release in the basal ganglia.
AB  - Dopamine (DA) is a key transmitter in the basal ganglia, yet DA transmission does
      not conform to several aspects of the classic synaptic doctrine. Axonal DA
      release occurs through vesicular exocytosis and is action potential- and Ca2+
      dependent. However, in addition to axonal release, DA neurons in midbrain exhibit
      somatodendritic release by an incompletely understood, but apparently exocytotic,
      mechanism. Even in striatum, axonal release sites are controversial, with
      evidence for DA varicosities that lack postsynaptic specialization, and largely
      extrasynaptic DA receptors and transporters. Moreover, DA release is often
      assumed to reflect a global response to a population of activities in midbrain DA
      neurons, whether tonic or phasic, with precise timing and specificity of action
      governed by other basal ganglia circuits. This view has been reinforced by
      anatomical evidence showing dense axonal DA arbors throughout striatum, and a
      lattice network formed by DA axons and glutamatergic input from cortex and
      thalamus. Nonetheless, localized DA transients are seen in vivo using
      voltammetric methods with high spatial and temporal resolution. Mechanistic
      studies using similar methods in vitro have revealed local regulation of DA
      release by other transmitters and modulators, as well as by proteins known to be
      disrupted in Parkinson's disease and other movement disorders. Notably, the
      actions of most other striatal transmitters on DA release also do not conform to
      the synaptic doctrine, with the absence of direct synaptic contacts for
      glutamate, GABA, and acetylcholine (ACh) on striatal DA axons. Overall, the
      findings reviewed here indicate that DA signaling in the basal ganglia is
      sculpted by cooperation between the timing and pattern of DA input and those of
      local regulatory factors.

PMID- 21939743
TI  - Association of angiotensin converting enzyme (ACE) gene I/D polymorphism and
      polycystic ovary syndrome (PCOS).
AB  - This study was conducted in Turkish patients with polycystic ovary syndrome to
      determine the frequency of I/D polymorphism genotypes of angiotensin converting
      enzyme gene, and to examine the role of this polymorphism in polycystic ovary
      syndrome development. Genomic DNA obtained from 200 persons (100 patients with
      polycystic ovary syndrome and 100 healthy controls) was used in the study. DNA
      was multiplied by polymerase chain reaction using I and D allele-specific
      primers. Polymerase chain reaction products were assessed with a charge coupled
      device (CCD) camera by being exposed to 2% agarose gel electrophoresis. There was
      statistically significant difference between the groups with respect to genotype
      distribution (p<0.001). The D allele frequency was indicated as 68% and I allele
      was as 32% in the patients, whereas it was 51.5-48.5% respectively in the control
      group. As a result of our study we may assert that angiotensin converting enzyme
      gene I/D polymorphism DD genotype should be considered as a genetic marker in
      polycystic ovary syndrome development in this Turkish study population.

PMID- 21939744
TI  - Genetic organization and molecular characterization of secA2 locus in Listeria
      species.
AB  - The translocation of proteins across the bacterial cell wall is carried out by
      the general secretory (Sec) system. Most bacteria have a single copy of the secA
      gene, with the exception of a few Gram-positive bacteria, which have an
      additional copy of secA, designated secA2. secA2 is present in Listeria
      monocytogenes and is responsible for secretion and translocation of several
      proteins including virulence factors; however, little is known about the secA2
      gene and its genetic organization in nonpathogenic members of the genus Listeria.
      The goal of this study was to determine the presence of secA2 locus and analyze
      the genetic relatedness among pathogenic and nonpathogenic Listeria species.
      Cloning experiments revealed that secA2 is present in all analyzed pathogenic (L.
      monocytogenes and L. ivanovii) and nonpathogenic (L. welshimeri, L. innocua, L.
      seeligeri, L. grayi and L. marthii) Listeria species except L. rocourtiae.
      Likewise, SecA2 transcripts were also detected in all species. Sequence analysis
      further revealed that 2331 nucleotides (776 amino acids) are conserved in L.
      monocytogenes, L. welshimeri, L. innocua and L. marthii. Three nucleotides are
      deleted in L. ivanovii and L. seeligeri and six in L. grayi, resulting in amino
      acid counts of 775, 775 and 774, respectively. secA2 is flanked upstream by iap
      (encoding p60) and downstream by a putative membrane protein (lmo0583, lmo
      f2365_0613) in all analyzed Listeria species, demonstrating conserved genetic
      organization of the secA2 locus in pathogenic and nonpathogenic species. Deletion
      of secA2 in L. innocua impaired accumulation of SecA2 substrate, N-acetyl
      muramidase (NamA) in the cell wall, providing evidence for the presence of
      functional SecA2 in nonpathogenic Listeria.

PMID- 21939745
TI  - Quantitative analysis of transcript variants of CHM gene containing LTR12C
      element in humans.
AB  - Choroideremia (CHM) is essential for the posttranslational activation of retina
      specific Rab protein. Transcript variants (a and b) of the CHM gene were detected
      in human cancer cells and tissues. Sequence analysis of the both variants found
      that isoform b is caused by an LTR12C element offering an alternative splicing
      site within the CHM gene. We performed real-time RT-PCR analysis to study
      expression levels of the CHM transcript variants in tumor and adjacent normal
      tissue samples. Our results showed that CHM isoform b was highly expressed in
      tumor tissues but its expression levels were relatively low in those of adjacent
      normal tissues including colon, testis, and lung. In addition, high expression
      levels of CHM isoform b were detected in the cancer cell lines of colon and lung,
      and colon cancer patient tissues. Thus, we suggest that expression levels of
      alternative transcripts of the CHM gene could be used as a molecular marker
      system to identify human cancers.

PMID- 21939746
TI  - A decrease of intracellular ATP is compensated by increased respiration and
      acidification at sub-lethal parathion concentrations in murine embryonic neuronal
      cells: measurements in metabolic cell-culture chips.
AB  - We present a label-free in vitro method for testing the toxic potentials of
      chemical substances using primary neuronal cells. The cells were prepared from 16
      day-old NMRI mouse embryos and cultured on silicon chips (www.bionas.de) under
      the influence of different parathion concentrations with sensors for respiration
      (Clark-type oxygen electrodes), acidification (pH-ISFETs) and cell adhesion
      (interdigitated electrode structures, IDES). After 12 days in vitro, the sensor
      readouts were simultaneously recorded for 350 min in the presence of parathion
      applying a serial 1:3 dilution. The parathion-dependent data was fitted by
      logistic functions. IC(50) values of approximately 105 MUM, 65 MUM, and 54 MUM
      were found for respiration, acidification, and adhesion, respectively. An IC(50)
      value of approximately 36 MUM was determined from the intracellular ATP-levels of
      cells, which were detected by an ATP-luminescence assay using micro-well plates.
      While the intracellular ATP level and cell adhesion showed no deviation from a
      simple logistic decay, increases of approximately 29% in the respiration and 15%
      in the acidification rates above the control values were found at low parathion
      concentrations, indicating hormesis. These increases could be fitted by a
      modified logistic function. We believe that the label-free, continuous, multi
      parametric monitoring of cell-metabolic processes may have applications in
      systems-biology and biomedical research, as well as in environmental monitoring.
      The parallel characterization of IC(50) values and hormetic effects may provide
      new insights into the metabolic mechanisms of toxic challenges to the cell.

PMID- 21939747
TI  - Lipoxygenase inhibitory activity of crude bark extracts and isolated compounds
      from Commiphora berryi.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Commiphora berryi is traditionally used for the
      treatment of cold and fever as well as for wound healing in the southern parts of
      India. AIM OF STUDY: The present study was designed to investigate in vitro
      soybean lipoxygenase inhibitory activity of crude extracts and compounds isolated
      from Commiphora berryi. MATERIALS AND METHODS: The bark of Commiphora berryi was
      extracted with different organic solvents and subjected to chromatographic
      separation for isolation of bioactive compounds. Structures of isolated compounds
      were elucidated by spectroscopic methods. The anti-inflammatory activity of bark
      extracts and bioactive compounds were assessed by in vitro soybean lipoxygenase
      (SBL) assay. RESULTS: 3beta-Hydroxyglutin-5-ene (1), friedelin (2), cycloeucaneol
      (3) nimbiol (4), sugiol (5), surianol (6), daucosterol (7) and ursolic acid (8)
      were isolated from crude bark extracts of the Commiphora berryi. The structure of
      nimbiol (4) was also confirmed by single crystal X-ray analysis. The petroleum
      ether, methanol, chloroform and ethyl acetate extracts of bark of Commiphora
      berryi showed SBL inhibitory activity with the IC(50) values of 15.3, 54.2, 71.5
      and 87.8 MUg/ml respectively. Among all the isolates, friedelin (2) showed
      significant SBL inhibitory activity with IC(50) 35.8 MUM. CONCLUSION: The overall
      results provide evidence that the studied plant might be a potential source of
      anti-inflammatory agents.

PMID- 21939748
TI  - Antimicrobial evaluation of Huilliche plant medicine used to treat wounds.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The traditional use of 40 plant species used for
      treatment of wounds and associated infections by the Huilliche people of Chile
      was evaluated against bacterial and fungal human pathogens, especially including
      wound pathogens. MATERIALS AND METHODS: The extracts were tested against the
      fungi Penicillium expansum, Candida albicans and the bacteria Bacillus subtilis,
      Pseudomonas aeruginosa (four different strains), Staphylococcus aureus,
      Escherichia coli (four different strains), Streptococcus pneumoniae (four
      different strains with one being resistance to streptomycin). RESULTS: Thirteen
      of the plant species have interesting antimicrobial activities, with that of
      Acaena argentea, Aristotelia chilensis, Blechnum chilense, Francoa appendiculta,
      Gevuina avellana and Laureliopsis philippiana being the most noteworthy.
      CONCLUSIONS: The findings in the manuscript support the traditional use by the
      Huilliche people, and allow enhanced economical benefit and use by the locals.
      The results obtained on Acaena argentea, Aristotelia chilensis, Blechnum
      chilense, Francoa appendiculta, Gevuina avellana and Laureliopsis philippiana are
      of specific scientific interest, and further studies is needed in order to
      establish the active constituents of the species.

PMID- 21939749
TI  - Cordyceps militaris extract stimulates Cl(-) secretion across human bronchial
      epithelia by both Ca(2+)(-) and cAMP-dependent pathways.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The caterpillar fungus Cordyceps militaris (CM;
      Clavicipitaceae) is a well-known traditional Chinese medicine that can be
      artificially cultivated on a large scale. We have previously demonstrated that
      its stimulatory action on ion transport in human airway epithelia is similar to
      Cordyceps sinensis (Clavicipitaceae), which has been traditionally used to treat
      respiratory diseases. AIM OF THE STUDY: To investigate the signal transduction
      mechanism(s) underlying CM-induced ion transport activity in cultured human
      bronchial epithelia. MATERIALS AND METHODS: 16HBE14o-, a human bronchial
      epithelial cell line, was used to study the regulation of ion transport by the
      water extract of CM. CM extract was added to the apical or basolateral aspect of
      the epithelia. In subsequent experiments, different Cl(-) channel and K(+)
      channel blockers, adenylate cyclase and protein kinase A (PKA) inhibitors, and an
      intracellular Ca(2+) chelator were used to examine the involvement of apical Cl(
      ) and basolateral K(+) channels in mediating CM-induced Cl(-) secretion and the
      underlying signal transduction mechanism(s). PKA activity was also measured in
      16HBE14o- cells. RESULTS: CM stimulated Cl(-) secretion across 16HBE14o-
      monolayers in a dose-dependent manner. Cl(-) secretion could be inhibited by
      apical application of the cystic fibrosis transmembrane conductance regulator
      (CFTR) Cl(-)channel blocker and the calcium-activated Cl(-) channel (CaCC)
      blocker. Cl(-) secretion was sensitive to basolateral application of different
      K(+) channel blockers. Similar inhibitory patterns were obtained in nystatin
      permeabilized epithelia. The CM-induced Cl(-) secretion could be inhibited by
      adenylate cyclase and PKA inhibitors as well as an intracellular Ca(2+) chelator.
      Data from the PKA assay suggested that CM extract caused a significant increase
      in PKA activity compared with untreated control epithelia. CONCLUSIONS: These
      results suggest that CM extract stimulated Cl(-) secretion across human bronchial
      epithelia, possibly via apical CFTR and CaCC, and the basolateral K(+) channels
      are involved in driving apical Cl(-) exit. The underlying signal transduction
      mechanisms involve both cAMP- and Ca(2+)-dependent pathways.

PMID- 21939750
TI  - Chemical analysis of incense smokes used in Shaxi, Southwest China: a novel
      methodological approach in ethnobotany.
AB  - AIM OF THE STUDY: Characterization and comparative analysis of the main VOCs
      (volatile organic compounds) present in the smoke of 11 experimentally combusted
      plant species used as incense in Shaxi, Southwest China. Substances which may be
      responsible for the pleasant smell of the smokes as well as substances with a
      potential pharmacological activity are discussed. MATERIALS AND METHODS: We adopt
      the dynamic headspace sorption method for the collection of smoke samples as a
      novel methodological approach in ethnobotany. The VOCs were identified using gas
      chromatography-mass spectrometry (GC-MS). Principal component analysis and
      canonical discriminant analysis were performed using PASW statistics (Version
      18.0.2). RESULTS: Among the identified compounds were 10 monoterpenoids, 7
      sesquiterpenoids, 6 linear hydrocarbons, 6 methoxy phenolics, 2 benzenoids, 2
      polycyclic aromatic hydrocarbons, and 2 fatty acids. Based on their volatile
      profiles, the species are well clustered intraspecifically and separated
      interspecifically. The most abundant among the compounds potentially responsible
      for the pleasant smells of the smokes are methyl salicylate (12.28+/-3.90%) for
      Gaultheria fragrantissima leaves, delta-cadinene (15.58+/-2.29%) for Juniperus
      squamata wood, and alpha-Pinene for Cupressus funebris branches (9.16+/-7.73%)
      and Pistacia weinmanniifolia branches (19.52+/-8.66%). A couple of substances
      found are known for pharmacological activity, such as methylsalycilate, beta
      caryophyllene and cedrol. CONCLUSIONS: The species used by the local people in
      Shaxi for incense differ clearly with respect to the chemical compounds of their
      smoke. Further, incense contains substances, which are of pharmacological
      interest and might support medicinal uses of smoke. Cedrol with its pleasant
      smell and sedative properties may be an important factor why specific plants are
      chosen as incense. Our findings support the idea that the effects of the use of
      incense as well as medicinal smoke depend on both, the cultural as well as the
      pharmacological context.

PMID- 21939751
TI  - Atherosclerosis is an old disease: Summary of the Ruffer Centenary Symposium, The
      Paleocardiology of Ancient Egypt, a meeting report of the Horus Study team.
AB  - A symposium in January 2011 "The Paleocardiology of Ancient Egypt" reviewed old
      and new evidence for the presence of advanced atherosclerotic lesions in ancient
      Egyptian mummies. This symposium was dedicated as a Centenary for the pioneering
      report of Marc Ruffer in 1911 (Ruffer, 1911). Based on CT scans, the Horus Study
      team concluded that atherosclerosis was present in the ancient Egyptian elites
      and is not a disease new to the 20th Century. Presentations included radiological
      data on vasculature, skeleton, and teeth, indicating degenerative diseases and
      poor health before age 50 in these specimens. Comparisons were made with the
      Bolivian Tsimane, a 20th Century population living without access to modern
      medicine with short life expectancy. Further research is needed to develop an
      epidemiological context for estimating population level prevalence of vascular
      disease and its risk factors in ancient Egyptian societies.

PMID- 21939752
TI  - Porphyromonas gingivalis induces RANKL in bone marrow stromal cells: involvement
      of the p38 MAPK.
AB  - Periodontitis is a bacterially-induced oral inflammatory disease that is
      characterised by tissue degradation and bone loss. Porphyromonas gingivalis is a
      gram negative bacterial species highly associated with the pathogenesis of
      chronic periodontitis. Receptor activator of nuclear factor-kB ligand (RANKL)
      induces bone resorption whilst osteoprotegerin (OPG) is a decoy receptor that
      blocks this process. Cyclooxygenase-2 (COX-2) is an enzyme responsible for the
      production of prostaglandin (PGE)(2,) which is a major inflammatory mediator of
      bone resorption. Mitogen-activated protein kinases (MAPK) are intracellular
      signalling molecules involved in various cell processes, including inflammation.
      This study aimed to investigate the effect of P. gingivalis on MAPKs and their
      involvement in the regulation of RANKL, OPG and COX-2 expression in bone marrow
      stromal cells. P. gingivalis challenge resulted in the phosphorylation of
      primarily the p38 MAPK. RANKL and COX-2 mRNA expressions were up-regulated,
      whereas OPG was down-regulated by P. gingivalis. The p38 synthetic inhibitor
      SB203580 abolished the P. gingivalis-induced RANKL and COX-2 expression, but did
      not affect OPG. Collectively, these results suggest that the p38 MAPK pathway is
      involved in the induction of RANKL and COX-2 by P. gingivalis, providing further
      insights into the pathogenic mechanisms of periodontitis.

PMID- 21939753
TI  - Psychoneuroimmunology: the whole and the sum of its parts.

PMID- 21939755
TI  - Neuropilin-1 regulates a new VEGF-induced gene, Phactr-1, which controls
      tubulogenesis and modulates lamellipodial dynamics in human endothelial cells.
AB  - Recently, we identified a new Vascular Endothelial Growth Factor (VEGF)-A(165)
      induced gene Phactr-1, (Phosphatase Actin Regulator-1). We reported that Phactr-1
      gene silencing inhibited tube formation in human umbilical endothelial cells
      (HUVECs) indicating a key role for Phactr-1 in tubulogenesis in vitro. In this
      study, we investigated the role of Phactr-1 in several cellular processes related
      to angiogenesis. We found that neuropilin-1 (NRP-1) and VEGF-R1 depletion
      inhibited Phactr-1 mRNA expression while NRP-2 and VEGF-R2 depletion had no
      effect. We described a new interaction site of VEGF-A(165) to VEGF-R1 in peptides
      encoded by exons 7 and 8 of VEGF-A(165). The specific inhibition of VEGF-A(165)
      binding on NRP-1 and VEGF-R1 by ERTCRC and CDKPRR peptides decreased the Phactr-1
      mRNA levels in HUVECs indicating that VEGF-A(165)-dependent regulation of Phactr
      1 expression required both NRP-1 and VEGF-R1 receptors. In addition, upon
      VEGFA(165)-stimulation Phactr-1 promotes formation and maintenance of cellular
      tubes through NRP-1 and VEGFR1. Phactr-1 was previously identified as protein
      phosphatase 1 (PP1) alpha-interacting protein that possesses actin-binding
      domains. We showed that Phactr-1 depletion decreased PP1 activity, disrupted the
      fine-tuning of actin polymerization and impaired lamellipodial dynamics. Taken
      together our results strongly suggest that Phactr-1 is a key component in the
      angiogenic process.

PMID- 21939754
TI  - Iron accumulation and neurotoxicity in cortical cultures treated with
      holotransferrin.
AB  - Nonheme iron accumulates in CNS tissue after ischemic and hemorrhagic insults and
      may contribute to cell loss. The source of this iron has not been precisely
      defined. After blood-brain barrier disruption, CNS cells may be exposed to plasma
      concentrations of transferrin-bound iron (TBI), which exceed that in the CSF by
      over 50-fold. In this study, the hypothesis that these concentrations of TBI
      produce cell iron accumulation and neurotoxicity was tested in primary cortical
      cultures. Treatment with 0.5-3mg/ml holotransferrin for 24h resulted in the loss
      of 20-40% of neurons, associated with increases in malondialdehyde, ferritin,
      heme oxygenase-1, and iron; transferrin receptor-1 expression was reduced by
      about 50%. Deferoxamine, 2,2'-bipyridyl, Trolox, and ascorbate prevented all
      injury, but apotransferrin was ineffective. Cell TBI accumulation was
      significantly reduced by deferoxamine, 2,2'-bipyridyl, and apotransferrin, but
      not by ascorbate or Trolox. After treatment with (55)Fe-transferrin,
      approximately 40% of cell iron was exported within 16h. Net export was increased
      by deferoxamine and 2,2'-bipyridyl, but not by apotransferrin. These results
      suggest that downregulation of transferrin receptor-1 expression is insufficient
      to prevent iron-mediated death when neurons are exposed to plasma concentrations
      of TBI. Chelator therapy may be beneficial for acute CNS injuries associated with
      loss of blood-brain barrier integrity.

PMID- 21939756
TI  - Natural substances and Alzheimer's disease: from preclinical studies to evidence
      based medicine.
AB  - Over the last 10 years, the potential therapeutic effects of nutraceuticals to
      prevent or delay Alzheimer's disease were proposed. Among dietary antioxidants
      curcumin, Ginkgo biloba and carnitines were extensively studied for their
      neuroprotective effects. The rationale for this alternative therapeutic approach
      was based on several preclinical studies which suggested the neuroprotective
      effects for curcumin, Ginkgo biloba and acetyl-l-carnitine due to either a free
      radical scavenging activity or the inhibition of pro-inflammatory pathways or the
      potentiation of the cell stress response. However, although these are interesting
      premises, clinical studies were not able to demonstrate significant beneficial
      effects of curcumin, Ginkgo biloba and acetyl-l-carnitine in improving cognitive
      functions in Alzheimer's disease patients. The aim of this review is to summarize
      the main pharmacologic features of curcumin, Ginkgo biloba and carnitines as well
      as to underlie the main outcomes reached by clinical studies designed to
      demonstrate the efficacy of these natural substances in Alzheimer's disease
      patients. This article is part of a Special Issue entitled: Antioxidants and
      Antioxidant Treatment in Disease.

PMID- 21939757
TI  - Expression of the megalin C-terminal fragment by macrophages during liver
      fibrogenesis in mice.
AB  - The low-density-lipoprotein receptor megalin (LRP2, gp330) is strongly expressed
      in the kidney, where it is responsible for the resorption of metabolites from
      primary urine. One of the main ligands is the complex of retinol and retinol
      binding protein. Megalin has been hypothesized to be part of the retinol storage
      system in liver. Considering the role of hepatic stellate cells in retinol
      storage and fibrogenesis we investigated mouse strains that developed different
      degrees of fibrosis after challenge with CCl(4). Immunoblotting revealed the
      invariable expression of the megalin C-terminal fragment independent of liver
      damage in all strains. However, only a specific cell population in centrilobular
      areas of fibrotic livers from DBA/2J mice, which were most susceptible for CCl(4)
      induced fibrogenesis in our study, was stained using megalin-specific antibodies.
      Double immunostaining indicated that a subset of hepatic macrophages might
      represent the megalin-expressing cells in fibrotic liver. Fluorescence activated
      cell sorting based isolation of hepatic macrophages and megalin specific
      expression analysis demonstrated the transcription of the whole megalin gene in
      liver macrophages. We argue that megalin might exhibit a proinflammatory effect
      by the uptake of retinoids in recruited monocytes, which thereby differentiate to
      liver macrophages and potentiate fibrogenesis by the release of proinflammatory
      mediators. Otherwise, megalin might be activated in macrophages during advanced
      fibrogenesis and act as a negative regulator of proinflammatory genes.

PMID- 21939758
TI  - Role of Vasa, Piwi, and Myc-expressing coelomic cells in gonad regeneration of
      the colonial tunicate, Botryllus primigenus.
AB  - In the colonial tunicate, Botryllus primigenus Oka, gonads consist of indifferent
      germline precursor cells, the primordial testis and ovary, and mature gonads, of
      which the immature gonad components can be reconstructed de novo in vascular buds
      that arise from the common vascular system, although the mechanism is uncertain.
      In this study, we investigated how and what kinds of cells regenerated the gonad
      components. We found that few Vasa-positive cells in the hemocoel entered the
      growing vascular bud, where their number increased, and finally developed
      exclusively into female germ cells. Simultaneously, small cell aggregates
      consisting of Vasa(-) and Vasa(+/-) cells appeared de novo in the lateral body
      cavity of developing vascular buds. Double fluorescent in situ hybridization
      showed that these cell aggregates were both Piwi- and Myc-positive. They could
      form germline precursor cells and a primordial testis and ovary that strongly
      expressed Vasa. Myc knockdown by RNA interference conspicuously lowered Piwi
      expression and resulted in the loss of germline precursor cells without affecting
      Vasa(+) oocyte formation. Myc may contribute to gonad tissue formation via Piwi
      maintenance. When human recombinant BMP 4 was injected in the test vessel,
      coelomic Piwi(+) cells were induced to express Vasa in the blood. We conclude,
      therefore, that in vascular buds of B. primigenus, female germ cells can develop
      from homing Vasa(+) cells in the blood, and that other gonad components can arise
      from coelomic Vasa(-)/Piwi(+)/Myc(+) cells.

PMID- 21939759
TI  - Novel selective Cox-2 inhibitors induce apoptosis in Caco-2 colorectal carcinoma
      cell line.
AB  - The cyclooxygenase-2 (COX-2) inhibitors including celecoxib inhibit cell growth
      and induce apoptosis in cancer cells. As COX-2 is over expressed in solid tumors
      such as colorectal cancer, it can be a suitable target for cancer treatment
      studies. In this study we designed and synthesized 4,5-bisaryl imidazolyl
      imidazoles as novel COX-2 inhibitors and evaluated their apoptosis inducing
      activities. The ability of our synthetic compounds to inhibit ovine COX-1 and COX
      2 was determined using a colorimetric method. The effects of these COX-2
      inhibitors and celecoxib on the proliferation of Caco-2 cells were evaluated by
      MTT assay. Cell apoptosis was determined by flow cytometry and DNA fragmentation
      assay. cDNA microarray technique was used to evaluate the effects of these
      synthetic compounds on 112 genes involved in apoptosis pathways. The expression
      of five apoptosis-related genes Bak-1, Bcl-x, BIRC (Survivin), TNFSF10 and CASP3
      were evaluated by quantitative real-time PCR. Among our synthetic compounds (3a
      c), 4,5-bis(4-methoxyphenyl)-1H-imidazol-2-yl derivative (compound 3c) exhibited
      the highest COX-1/COX-2 selectivity index (SI=262.9) and lowest growth inhibitory
      concentration (IC(50)=21.20MUM). In addition, compounds 3a-c could up-regulate
      pro-apoptotic genes and down-regulate anti-apoptotic genes. So, these synthetic
      compounds seem to be inducers of apoptosis in Caco-2 cell line. This study
      indicates that 4,5-bisaryl imidazolyl imidazole is a suitable scaffold to design
      COX-2 inhibitors and 4,5-bis(4-methoxyphenyl)-1H-imidazol-2-yl derivative
      exhibited highly COX-2 inhibitory potency and selectivity even more than
      celecoxib. It seems that it could induce apoptosis in Caco-2 colorectal carcinoma
      cell line.

PMID- 21939760
TI  - A three-layered model of primate prefrontal cortex encodes identity and abstract
      categorical structure of behavioral sequences.
AB  - Categorical encoding is crucial for mastering large bodies of related sensory
      motor experiences, but what is its neural substrate? In an effort to respond to
      this question, recent single-unit recording studies in the macaque lateral
      prefrontal cortex (LPFC) have demonstrated two characteristic forms of neural
      encoding of the sequential structure of the animal's sensory-motor experience.
      One population of neurons encodes the specific behavioral sequences. A second
      population of neurons encodes the sequence category (e.g. ABAB, AABB or AAAA) and
      does not differentiate sequences within the category (Shima, K., Isoda, M.,
      Mushiake, H., Tanji, J., 2007. Categorization of behavioural sequences in the
      prefrontal cortex. Nature 445, 315-318.). Interestingly these neurons are
      intermingled in the lateral prefrontal cortex, and not topographically
      segregated. Thus, LPFC may provide a neurophysiological basis for sensorimotor
      categorization. Here we report on a neural network simulation study that
      reproduces and explains these results. We model a cortical circuit composed of
      three layers (infragranular, granular, and supragranular) of 5*5 leaky integrator
      neurons with a sigmoidal output function, and we examine 1000 such circuits
      running in parallel. Crucially the three layers are interconnected with recurrent
      connections, thus producing a dynamical system that is inherently sensitive to
      the spatiotemporal structure of the sequential inputs. The model is presented
      with 11 four-element sequences following Shima et al. We isolated one
      subpopulation of neurons each of whose activity predicts individual sequences,
      and a second population that predicts category independent of the specific
      sequence. We argue that a richly interconnected cortical circuit is capable of
      internally generating a neural representation of category membership, thus
      significantly extending the scope of recurrent network computation. In order to
      demonstrate that these representations can be used to create an explicit
      categorization capability, we introduced an additional neural structure
      corresponding to the striatum. We showed that via cortico-striatal plasticity,
      neurons in the striatum could produce an explicit representation both of the
      identity of each sequence, and its category membership.

PMID- 21939761
TI  - A reduced model of DA neuronal dynamics that displays quiescence, tonic firing
      and bursting.
AB  - Midbrain dopaminergic neurons send numerous projections to cortical and sub
      cortical areas, and in a manner dependent upon their activities, diffusely
      release dopamine (DA) to their targets. Recent experimental studies have shown
      that DAergic neuronal bursting is associated with a significantly greater degree
      of DA release than an equivalent tonic activity pattern. Past computational
      models for DA cell activity relied upon somatodendritic mechanisms in order to
      generate DA neuronal bursting. However, recent experimental studies indicate that
      burst firing can be generated somatically with the dendrites silenced. These
      somatically induced bursts have characteristics consistent with normal bursting,
      suggesting that a single-compartmental model should be sufficient for generating
      the observed DA neuronal dynamics. In this work, we introduce such a model for DA
      neuronal dynamics and demonstrate that this model captures the qualitative
      behavior of DAergic neuronal dynamics: quiescence, tonic firing and bursting. In
      our conductance-based approach, the interplay between the L-type calcium and the
      calcium dependent SK potassium channel provides a scaffold for the underlying
      oscillation for the pacemaker-like firing patterns. The model includes terms
      which can selectively block the SK conductance, which would correspond to
      pharmacological manipulations using the drug apamin. Our modeling studies are in
      line with experimental evidence that a reduction of the SK conductance often
      induces DA neuronal bursting. Moreover, our model can reproduce findings that
      burst firing can be elicited via stimulus driven events, manifested by rises in
      the amount of NMDA. This model for DA cell activity could be further sculpted to
      include more detailed second messenger signaling processes in order to elucidate
      key differences between the two principal classes of midbrain DA neurons: those
      of the ventral tegmental area and the substantia nigra pars compacta.

PMID- 21939762
TI  - Synthesizing complex movement fragment representations from motor cortical
      ensembles.
AB  - We have previously shown that the responses of primary motor cortical neurons are
      more accurately predicted if one assumes that individual neurons encode
      temporally-extensive movement fragments or preferred trajectories instead of
      static movement parameters (Hatsopoulos et al., 2007). Building on these
      findings, we examine here how these preferred trajectories can be combined to
      generate a rich variety of preferred movement trajectories when neurons fire
      simultaneously. Specifically, we used a generalized linear model to fit each
      neuron's spike rate to an exponential function of the inner product between the
      actual movement trajectory and the preferred trajectory; then, assuming
      conditional independence, when two neurons fire simultaneously their spiking
      probabilities multiply implying that their preferred trajectories add. We used a
      similar exponential model to fit the probability of simultaneous firing and found
      that the majority of neuron pairs did combine their preferred trajectories using
      a simple additive rule. Moreover, a minority of neuron pairs that engaged in
      significant synchronization combined their preferred trajectories through a small
      scaling adjustment to the additive rule in the exponent, while preserving the
      shape of the predicted trajectory representation from the additive rule. These
      results suggest that complex movement representations can be synthesized in
      simultaneously firing neuronal ensembles by adding the trajectory representations
      of the constituents in the ensemble.

PMID- 21939763
TI  - Compounding of a topical drug with prospective natural surfactant-stabilized
      pharmaceutical bases: physicochemical and in vitro/in vivo characterization--a
      ketoprofen case study.
AB  - Recently, healthcare professionals again began realizing the benefits of
      preparing customized medications to meet specific patient needs. The objective of
      this work was to develop and evaluate simple pharmaceutical bases stabilized with
      natural-origin surfactant of alkyl polyglucoside (APG) type as prospective ready
      to-use bases and compare them to widely used pharmacopoeial ones. Additionally,
      the ability of the formulated bases to sustain isopropyl alcohol was assessed as
      well as its influence on ketoprofen skin absorption (as a co-solvent and
      potential penetration enhancer). In order to evaluate the manifold
      characteristics a topical drug product should possess, a comprehensive
      characterization was performed using different techniques. Physicochemical
      characterization demonstrated satisfactory physical stability of APG-stabilized
      bases upon the addition of alcohol. In vitro release/permeation studies failed to
      show significant difference in ketoprofen liberation/permeation profiles from
      different bases. However, the extent of ketoprofen delivery in vivo was clearly
      increased from APG bases, relative to that obtained from pharmacopoeia quality
      one, implying a distinct influence of the emulsion systems' colloidal structures.
      Taking also into account the rheological behavior of APG bases, revealing their
      ameliorated sensory characteristics, it could be concluded that the investigated
      APG bases could be considered as preferential option in drug compounding related
      to the conventional ones.

PMID- 21939764
TI  - Effect of CYP19 rs6493497 and rs7176005 haplotype status on in vivo aromatase
      transcription, plasma and tissue estrogen levels in postmenopausal women.
AB  - High plasma levels of estradiol (E(2)) are correlated to increased breast cancer
      risk in postmenopausal women. Recently, a study reported two single nucleotide
      polymorphisms (SNPs) (rs6493497; C->T and rs7176005; G->A) in the aromatase
      (CYP19) promoter 1.1 to be associated with elevated plasma E(2) levels, most
      likely due to enhanced transcription. In silico predictions suggested increased
      transcription factor binding for the rs7176005_A allele. We genotyped 46 breast
      cancer patients for rs6493497 and rs7176005 status and assessed the potential
      association between CYP19 SNP status and (i) CYP19 mRNA levels in tumour and
      normal breast tissue, and (ii) estrogen levels in plasma, tumour and normal
      breast tissue. In addition, we measured CYP19 SNP status and correlated it to
      plasma estrogen levels in a confirmatory dataset of 108 healthy postmenopausal
      women. We found no correlation between either of the two SNPs and CYP19 mRNA
      level. In the breast cancer patients, the rs6493497_T/rs7176005_A variant
      haplotype was associated with low plasma estrone (E(1)) (p=0.038) and low E(2)
      (p=0.050) levels; however, no correlation was recorded between SNP status and
      plasma estrogen levels in the cohort of 108 healthy postmenopausal women. Our
      findings indicate rs6493497 and rs7176005 status not to enhance CYP19
      transcription or increase estrogen levels in postmenopausal women.

PMID- 21939765
TI  - FOXP3+ regulatory T cells: from suppression of rejection to induction of renal
      allograft tolerance.
AB  - Naturally occurring and induced regulatory T cells (Tregs) can become
      hyporesponsive and anergic to antigen stimulation in autoimmune diseases and
      allograft rejection. The mechanisms of suppression of effector T cells by Tregs
      remain unclear, but there are in vitro and in vivo evidences showing that these
      cells are able to suppress antigen-specific responses via direct cell-to-cell
      contact, secrete anti-inflammatory cytokines such as TGF-beta and IL-10, and
      inhibit the generation of memory T cells, among others. The transcription factor
      FOXP3 is a specific marker of Tregs and its deficiency is associated with
      autoimmune diseases and inflammation. During acute rejection of kidney
      allografts, an augmented FOXP3 gene expression as well as increased
      CD4(+)CD25(+)FOXP3(+) and other cell populations are observed in graft biopsies.
      However, it is not clear whether Tregs migrate into the graft and are retained
      there to suppress the inflammatory process, or whether they are directly
      associated with more complex mechanisms to induce immune tolerance. FOXP3(+)
      Tregs may direct the immune response toward a graft acceptance program,
      potentially affecting the long-term survival of transplanted organs and tissues.
      Immunosuppressive drugs modulate the number and function of circulating Tregs and
      FOXP3 expression. Experimental and clinical studies have shown that mTOR
      inhibitors have positive and calcineurin inhibitors negative effects on Tregs,
      but it is difficult to set apart the effect of multiple other factors known to be
      associated with short- and long-term renal graft outcomes. This review aimed to
      describe the functions of Tregs and its transcription factor FOXP3 in suppression
      of immune response during rejection and in induction of kidney graft tolerance,
      as well as to review the individual effects of immunosuppressive drugs on Tregs.

PMID- 21939766
TI  - Brief report: Why did two patients who type for HLA-B13 have antibodies that
      react with all Bw4 antigens except HLA-B13?
AB  - Two transplant candidates sensitized during pregnancy by a B*44:02 mismatch
      showed antibodies that reacted with an epitope defined by the 145R+82LR eplet
      pair shared by all Bw4 antigens in single allele Luminex panels except B13. Both
      eplets are on one or more alleles of the antibody producer and according to
      HLAMatchmaker, they are considered intralocus and interlocus matches which should
      not induce antibodies. The recently developed nonself-self paradigm for HLA
      epitope immunogenicity has offered a ready explanation why the pair of self-145R
      and self-82LR eplets on B*44:02 induced specific antibodies. This finding is
      consistent with the concept that alloantibody responses originate from B-cells
      with self-HLA immunoglobulin receptors.

PMID- 21939767
TI  - EpHLA: an innovative and user-friendly software automating the HLAMatchmaker
      algorithm for antibody analysis.
AB  - The global challenge for solid organ transplantation programs is to distribute
      organs to the highly sensitized recipients. The purpose of this work is to
      describe and test the functionality of the EpHLA software, a program that
      automates the analysis of acceptable and unacceptable HLA epitopes on the basis
      of the HLAMatchmaker algorithm. HLAMatchmaker considers small configurations of
      polymorphic residues referred to as eplets as essential components of HLA
      epitopes. Currently, the analyses require the creation of temporary files and the
      manual cut and paste of laboratory tests results between electronic spreadsheets,
      which is time-consuming and prone to administrative errors. RESULTS: The EpHLA
      software was developed in Object Pascal programming language and uses the
      HLAMatchmaker algorithm to generate histocompatibility reports. The automated
      generation of reports requires the integration of files containing the results of
      laboratory tests (HLA typing, anti-HLA antibody signature) and public data banks
      (NMDP, IMGT). The integration and the access to this data were accomplished by
      means of the framework called eDAFramework. The eDAFramework was developed in
      Object Pascal and PHP and it provides data access functionalities for software
      developed in these languages. The tool functionality was successfully tested in
      comparison to actual, manually derived reports of patients from a renal
      transplantation program with related donors. CONCLUSIONS: We successfully
      developed software, which enables the automated definition of the epitope
      specificities of HLA antibodies. This new tool will benefit the management of
      recipient/donor pairs selection for highly sensitized patients.

PMID- 21939768
TI  - Dysfunction of neurogenic VIP-mediated relaxation in mouse distal colon with
      dextran sulfate sodium-induced colitis.
AB  - Vasoactive intestinal peptide (VIP) regulates various functions including
      motility and immune homeostasis in colon. The VIP system including its receptors
      has been established to control the development of ulcerative colitis, but the
      functional changes of the system-regulated motility in colon with ulcerative
      colitis are not well understood. In this study, we investigated VIP-related
      contractile responses in distal colon from mice with dextran sulfate sodium (DSS)
      induced acute colitis. Electrical stimulation (ES) under our conditions caused
      relaxation during ES and contraction after withdrawal of ES in a tetrodotoxin
      sensitive manner. Pharmacological analyses showed two phases of ES-induced
      relaxation: a transient neuronal nitric oxide (NO) synthase-dependent phase (I),
      and a continued VIP receptor-mediated phase (II). Inhibition of VIP receptors and
      protein kinase A decreased both phases. In colon from DSS-treated mice, ES
      induced phase II (also phase I) and VIP-induced, but not cyclic AMP analog
      induced, relaxation were decreased. Stimulation with VIP significantly increased
      cyclic AMP formation in colon preparations from control but not DSS-treated mice.
      In colon from DSS-treated mice, the basal cyclic AMP level was markedly greater
      without changes in the level of VIP receptor VPAC(2). Isoprenaline- and forskolin
      induced relaxation and cyclic AMP formation were not changed by DSS treatment.
      These findings suggest that dysfunction of VIP receptors in muscles, in addition
      to loss of the neuronal VIP and NO pathways, are involved in abnormal motility in
      mouse colon with DSS-induced colitis.

PMID- 21939769
TI  - Utilization of fluorescently-labeled tetracysteine-tagged proteins to study virus
      entry by live cell microscopy.
AB  - Viruses exploit cellular machinery to gain entry and initiate their replication
      cycle within host cells. The development of methods to visualize virus entry in
      live cells has provided new insights to the cellular processes involved in virus
      entry and the intracellular locations where viral payloads are deposited. The use
      of fluorescently labeled virus and high-resolution microscopy is currently the
      method of choice to study virus entry in live cells. While fluorescent protein
      fusions (e.g. viral proteins fused to GFP) have been used, the labeling of viral
      proteins that contain a small tetracysteine (tc) tag with biarsenical fluorescent
      compounds (e.g. FlAsH, ReAsH, Lumio-x) offers several advantages over
      conventional xFP-fusion constructs. This article describes methods for generating
      fluorescently labeled viruses encoding tc-tagged proteins that are suitable for
      the study of virus entry in live cells by fluorescence microscopy. Critical
      parameters required to quantify fluorescence signals from the labeled, tc-tagged
      proteins in individual virus particles during the entry process and the
      subsequent fate of the labeled viral proteins after virus uncoating are also
      described.

PMID- 21939770
TI  - MARCH5 gene is duplicated in rainbow trout, but only fish-specific gene copy is
      up-regulated after VHSV infection.
AB  - Ubiquitination regulates the activity, stability, and localization of a wide
      variety of proteins. Several mammalian MARCH ubiquitin E3 ligase proteins have
      been suggested to control cell surface immunoreceptors. The mitochondrial protein
      MARCH5 is a positive regulator of Toll-like receptor 7-mediated NF-kappaB
      activation in mammals. In the present study, duplicated MARCH5-like cDNA
      sequences were isolated from rainbow trout (Oncorhynchus mykiss) comprising open
      reading frames of 882 bp (MARCH5A) and 885 bp (MARCH5B), respectively. Trout
      MARCH5A and MARCH5B-encoding sequences share only 65% sequence identity.
      Phylogenetic analyses including an additionally isolated MARCH5-like sequence
      from whitefish (Coregonus maraena) suggest that teleosts possess an additional
      MARCH5 gene copy resulting from a fish-specific whole genome duplication. Coding
      sequences of MARCH5A and MARCH5B genes from trout are distributed over six exons.
      Hypothetical MARCH5 proteins from trout comprise four transmembrane helices and a
      single motif similar to a RING variant domain (RINGv) including eight highly
      conserved cysteine and histidine residues. A 'reverse-northern blot' analysis
      revealed furthermore a MARCH5B Deltaexon5 transcript variant. Both MARCH5 genes
      from trout show a strain-, tissue- and cell-specific expression profile
      indicating different functional roles. Fish-specific MARCH5A gene for instance
      might be involved in defense mechanisms, since in vivo-challenge with the viral
      pathogen VHSV caused a significant 1.7-fold elevated copy number of the
      respective gene in gills four days after infection, whereas MARCH5B transcript
      level did not increase.

PMID- 21939771
TI  - Identification and expressional analysis of two cathepsins from half-smooth
      tongue sole (Cynoglossus semilaevis).
AB  - Cathepsins are a family of lysosomal proteases that play an important role in
      protein degradation, antigen presentation, apoptosis, and inflammation.
      Cathepsins are divided into three groups, i.e., cysteine protease, serine
      protease, and aspartic protease. Cathepsin D and cathepsin L, which are aspartic
      protease and cysteine protease respectively, have been identified in a number of
      teleosts; however, the immunological relevance of fish cathepsins is largely
      unknown. In this study, we cloned and analyzed the expression profiles of a
      cathepsin D (CsCatD) and a cathepsin L (CsCatL) homologs from half-smooth tongue
      sole (Cynoglossus semilaevis). CsCatD is composed of 396 amino acid residues and
      shares 67.6-88.4% overall sequence identities with fish and human cathepsin D.
      Structurally CsCatD possesses an aspartic endopeptidase domain, which contains
      two conserved aspartic acid residues that form the catalytic site. CsCatL is 336
      residues in length and shares 64.7-90.2% overall sequence identities with fish
      and human cathepsin L. CsCatL has an N-terminal cathepsin propeptide inhibitor
      domain followed by a Papain family cysteine protease domain, the latter
      containing four conserved catalytic residues: Gln-133, Cys-139, His-279, and Asn
      303. Recombinant CsCatL purified from Escherichia coli exhibited apparent
      protease activity. Quantitative real time RT-PCR analysis detected constitutive
      expression of CsCatD and CsCatL in multiple tissues, with the lowest level found
      in heart and the highest level found in liver. Experimental challenge of tongue
      sole with the bacterial pathogen Vibrio anguillarum and megalocytivirus caused
      significant inductions of both CsCatD and CsCatL expression in kidney and spleen
      in time-dependent manners. Immunization of the fish with a subunit vaccine also
      enhanced CsCatD and CsCatL expression in the first week post-vaccination. These
      results suggest involvement of CsCatD and CsCatL in host immune reactions to
      bacterial and viral infections and in the process of antigen-induced immune
      response.

PMID- 21939772
TI  - Probabilistic inference of regularisation in non-rigid registration.
AB  - A long-standing issue in non-rigid image registration is the choice of the level
      of regularisation. Regularisation is necessary to preserve the smoothness of the
      registration and penalise against unnecessary complexity. The vast majority of
      existing registration methods use a fixed level of regularisation, which is
      typically hand-tuned by a user to provide "nice" results. However, the optimal
      level of regularisation will depend on the data which is being processed; lower
      signal-to-noise ratios require higher regularisation to avoid registering image
      noise as well as features, and different pairs of images require registrations of
      varying complexity depending on their anatomical similarity. In this paper we
      present a probabilistic registration framework that infers the level of
      regularisation from the data. An additional benefit of this proposed
      probabilistic framework is that estimates of the registration uncertainty are
      obtained. This framework has been implemented using a free-form deformation
      transformation model, although it would be generically applicable to a range of
      transformation models. We demonstrate our registration framework on the
      application of inter-subject brain registration of healthy control subjects from
      the NIREP database. In our results we show that our framework appropriately
      adapts the level of regularisation in the presence of noise, and that inferring
      regularisation on an individual basis leads to a reduction in model over-fitting
      as measured by image folding while providing a similar level of overlap.

PMID- 21939774
TI  - In vivo magnetic resonance imaging of ferritin-based reporter visualizes native
      neuroblast migration.
AB  - Adult neurogenesis research in mammals presents a challenge as most stem cells
      and progenitors are located deep in opaque brain tissues. Here, we describe an
      efficient ferritin-based magnetic resonance imaging (MRI) reporter and its use to
      label mouse subventricular zone progenitors, enabling in vivo visualization of
      endogenous neuroblast migration toward the olfactory bulb. We quantify the effect
      of the ferritin transgene expression on cellular iron transport proteins such as
      transferrin receptor, divalent metal transporter and STEAP reductase. Based on
      these data, we elucidate key aspects of the cellular pathways that the reporter
      utilizes to load iron and form its superparamagnetic core. This MRI reporter gene
      platform can facilitate the non-invasive study of native or transplanted stem
      cell migration and associated neurogenic or therapeutic molecular events in live
      animals.

PMID- 21939773
TI  - Impact of state anxiety on the interaction between threat monitoring and
      cognition.
AB  - How does threat processing impact cognitive performance? To investigate this
      question, in the present functional magnetic resonance imaging study,
      participants performed a response-conflict task (neutral, congruent, and
      incongruent trials) that followed a variable-length shock anticipation period or
      a corresponding delay during which they would not be shocked. The delay period
      was cued by a geometric-shaped stimulus indicating whether the subject was in the
      safe (no shock) or threat (potential shock) condition. Behaviorally, participants
      showed increased reaction time interference (incongruent-neutral) during threat
      trials, an effect that increased as a function of state anxiety level across
      participants. Brain imaging data were analyzed for the cue and the subsequent
      target phase of the task. At the target phase, the left anterior insula exhibited
      interaction-type responses (i.e., increased interference during threat trials)
      that were positively associated with state anxiety level - a relationship that
      paralleled the behavioral pattern. At the cue phase, greater responses to threat
      vs. safe were observed in a circuit of regions, including the medial PFC,
      anterior insula, thalamus, and bed nucleus of the stria terminalis/caudate, which
      we interpreted as engaged by shock monitoring/anticipation processes. In
      contrast, intriguingly, greater responses to safe vs. threat at the cue phase
      were observed in a broader set of regions that overlapped with the "resting
      state" network. Finally, a standard statistical mediation analysis revealed that
      the relationship between state anxiety scores and interference-related responses
      in the left anterior insula during the target phase was partially mediated via
      cue responses in the medial PFC, consistent with the idea that more anxious
      individuals had difficulty in engaging the medial PFC during the threat
      condition. Taken together, our findings suggest that threat monitoring impairs
      the upcoming resolution of interference. Furthermore, a confluence of effects of
      cognitive task condition, threat, and individual differences in state anxiety was
      observed in the anterior insula, a structure that is suggested to be particularly
      important for the interaction between emotion and cognition.

PMID- 21939775
TI  - Microstructure of a three-way anatomical network predicts individual differences
      in response inhibition: a tractography study.
AB  - Response inhibition is thought to depend critically on the inferior frontal
      gyrus, pars opercularis (IFGoper), presupplementary motor area (preSMA) and basal
      ganglia, including the subthalamic nucleus (STN), but the differential
      contribution of structural connections within this network to response inhibition
      remains unclear. Using diffusion tensor imaging and probabilistic fiber
      tractography, we investigated the relative associations between local white
      matter microstructure and stop-signal response inhibition in fronto-basal ganglia
      tracts delineated by probabilistic tractography. In a tract-of-interest approach,
      we identify significant associations with fractional anisotropy (FA) in fibers
      connecting the right STN region to both preSMA/SMA and IFGoper and in bilateral
      tracts connecting preSMA/SMA to IFGoper and the striatum. In addition,
      significant associations with radial diffusivity (RD) were found in fibers
      connecting the right preSMA/SMA to striatum and in bilateral tracts between
      IFGoper and STN region. In our whole-brain analysis, additional significant
      clusters were identified in the corpus callosum, optic radiation, inferior fronto
      occipital tract and white matter of the precentral gyrus. To investigate the
      relative importance of regional white matter characteristics to response
      inhibition performance, we performed a step-wise multiple regression analysis
      that yielded FA in tracts connecting preSMA/SMA to the STN region and striatum,
      respectively, and RD in fibers connecting IFGoper to the STN region as best
      predictors of response inhibition performance (42% explained variance). These
      findings point to a specific contribution of white matter pathways connecting
      distinct basal ganglia structures with both medial frontal and ventrolateral
      prefrontal regions to response inhibition.

PMID- 21939776
TI  - The great brain versus vein debate.
AB  - From the earliest fMRI experiments, it was quickly appreciated by those working
      with BOLD at high field that the signal change originated from visible veins
      whose spatial localization was relatively coarse ("the macrovasculature"), and
      smaller vessels ("the microvasculature") that were not individually visible in
      BOLD images. It was expected that a functional brain imaging technique that was
      predominantly sensitive to the macrovasculature would not have the same effective
      resolution as one sensitive to the microvasculature. Elimination of the venous
      signal and enhancement of the microvascular one offered the tantalizing ability
      to image columnar and lamellar structures in the brain and distinguished fMRI
      from its predecessor techniques. This article reviews a brief history of how
      these signal sources were first identified and separated and some of the
      controversy associated with the "brain versus vein" debate.

PMID- 21939777
TI  - Molecular phylogeny of extant horseshoe crabs (Xiphosura, Limulidae) indicates
      Paleogene diversification of Asian species.
AB  - Horseshoe crabs are marine invertebrates well known for their exceptionally low
      rates of diversification during their entire evolutionary history. Despite the
      low species diversity in the group, the phylogenetic relationships among the
      extant species, especially among the three Asian species are still unresolved.
      Here we apply a new set of molecular genetic data in combination with a wide
      geographic sampling of the intra-specific diversity to reinvestigate the
      evolutionary history among the four living limulid xiphosurans. Our analysis of
      the intraspecific diversity reveals low levels of connectivity among
      Carcinoscorpius rotundicauda lineages, which can be explained by the estuarine
      bound ecology of this species. Moreover, a clear genetic break across the Thai
      Malay Peninsula suggests the presence of cryptic species in C. rotundicauda. The
      limulid phylogeny finds strong support for a monophyletic genus Tachypleus and a
      diversification of the three Asian species during the Paleogene period, with
      speciation events well separated in time by several million years. The tree
      topology suggests that the three Asian species originated in central South East
      Asia from a marine stem group that inhabited the shallow coastal waters between
      the Andaman Sea, Vietnam, and Borneo. In this region C. rotundicauda probably
      separated from the Tachypleus stem group by invading estuarine habitats, while
      Tachypleus tridentatus most likely migrated northeast along the Southern coast of
      China and towards Japan.

PMID- 21939778
TI  - Modulation of bacterial translocation in mice mediated through lactose and human
      milk oligosaccharides.
AB  - Massive resection of the small intestine in infants is imposed to the regulation
      of several intestinal pathological situations, as intestinal adaptation cannot be
      relied upon. Many nutritional disturbances are occurring following surgery
      procedure. In this vein, long-term parenteral feeding is adopt to improve
      prognosis not always successfully. Clostridia and more specifically Clostridium
      perfringens, are suspected to participate in the physiopathology of the rising
      situation. In order to investigate the effect of lactose and human milk neutral
      oligosaccharides (HMNOs) on Clostridia, germfree mice were inoculated either with
      enterotoxigenic C.perfringens strain isolated from a patient with NEC, or with a
      human microbiota harboring C.clostridioforme group(HF). In this vein, different
      doses of lactose were administrated during 2 weeks in adult mice on an attempt to
      evaluate the lactase activity. Intake of lactose (70 g/L) and HMNOs (7 g/L) in
      C.perfringens monoassociated mice induced mortality within a week. In HF mice, no
      mortality was observed. An increase in Clostridia occurrence was observed in the
      median ileum after intake of 7 g lactose (p = 0.017). Higher clostridial numbers
      occurred in caecum following intake of 70 g lactose (p < 0.05) and HMNOs (p <
      0.025). Bifidobacteria were found increased from distal ileum to colon following
      70 g of lactose intake, whereas they decreased in the caecum of mice drinking
      lower lactose concentrations. Finally, bacteremia was more frequent in 70 g
      lactose/L mice (p < 0.02), whereas at lower doses of lactose bifidobacterial
      translocation was observed. As a result, human milk oligosaccharides could favor
      clostridial population when reaching the lower intestine. The shortness of the
      small intestine in infants underwent massive intestinal resection seems to be
      associated to an incomplete breakdown of lactose. Enteral feeds formulas deprived
      in lactose would be more suitable in enteral feeding of infants.

PMID- 21939779
TI  - Micronutrient and mineral supply in developmental biology.

PMID- 21939780
TI  - Fibroblast growth factor 2 and protein kinase C alpha are involved in syndecan-4
      cytoplasmic domain modulation of turkey myogenic satellite cell proliferation.
AB  - Syndecan-4 core protein is composed of extracellular, transmembrane, and
      cytoplasmic domains. The cytoplasmic domain functions in transmitting signals
      into the cell through the protein kinase C alpha (PKCalpha) pathway. The
      glycosaminoglycan (GAG) and N-linked glycosylated (N-glycosylated) chains
      attached to the extracellular domain influence cell proliferation. The current
      study investigated the function of syndecan-4 cytoplasmic domain in combination
      with GAG and N-glycosylated chains in turkey muscle cell proliferation,
      differentiation, fibroblast growth factor 2 (FGF2) responsiveness, and PKCalpha
      membrane localization. Syndecan-4 or syndecan-4 without the cytoplasmic domain
      and with or without the GAG and N-glycosylated chains were transfected or co
      transfected with a small interfering RNA targeting syndecan-4 cytoplasmic domain
      into turkey muscle satellite cells. The overexpression of syndecan-4 mutants
      increased cell proliferation but did not change differentiation. Syndecan-4
      mutants had increased cellular responsiveness to FGF2 during proliferation.
      Syndecan-4 increased PKCalpha cell membrane localization, whereas the syndecan-4
      mutants decreased PKCalpha cell membrane localization compared to syndecan-4.
      However, compared to the cells without transfection, syndecan-4 mutants increased
      cell membrane localization of PKCalpha. These data indicated that the syndecan-4
      cytoplasmic domain and the GAG and N-glycosylated chains are critical in syndecan
      4 regulating satellite cell proliferation, responsiveness to FGF2, and PKCalpha
      cell membrane localization.

PMID- 21939782
TI  - Synthetic LXR agonist T0901317 attenuates lipopolysaccharide-induced acute lung
      injury in rats.
AB  - OBJECTIVE: To investigate the potential role of synthetic liver X receptors
      (LXRs) agonists T0901317 in lung of rats with acute lung injury induced by
      lipopolysaccharide (LPS). METHODS: Rats infused with LPS served as acute lung
      injury (ALI) models. Specific mRNA was quantified by semi-quantitative reverse
      transcription polymerase (RT-PCR) and protein expression by western blotting.
      Inflammatory cytokine and MPO activity assays were studied by ELISA.
      Histopathology analysis was evaluated by hematoxylin and eosin. RESULTS: The
      expressions of LXRalpha and LXRbeta were gradually decreased after LPS challenge.
      T0901317 pretreatment efficiently reduced the production of TNF-alpha, IL-1beta,
      and IL-6, while elevated the level of IL-10 in BALF of rats with ALI. T0901317
      also decreased the number of inflammatory cells and the concentration of total
      proteins in the BALF. Compared with the LPS group, rats with ALI which were
      pretreated with T0901317 had lower pulmonary tissue MPO activity and lightened
      histopathologic changes of lung. Furthermore, the expressions of NF-kappaB and
      ICAM-1 were markedly reduced after T0901317 administration. CONCLUSION: The
      expressions of LXRs were significantly decreased and synthetic agonist T0901317
      suppresses lung inflammatory responses and lightened histopathologic changes of
      lung in rats with ALI. The mechanisms of this action for T0901317 may associate
      with the inhibition of NF-kappaB activation and downregulation of adhesion
      molecules ICAM-1 gene.

PMID- 21939783
TI  - Melittin inhibits cerulein-induced acute pancreatitis via inhibition of the JNK
      pathway.
AB  - The major compound of bee venom, melittin, has been used as an anti-inflammatory
      reagent for decades. However, the potential of melittin to ameliorate acute
      pancreatitis (AP) is unknown. Our aim was to investigate the effect of melittin
      on cerulein-induced AP. Pre- and post-treatment with melittin inhibited
      histological changes in the pancreas and lungs during cerulein-induced AP.
      Pancreatic weight/body weight ratios; digestive enzymes, including amylase and
      lipase; serum and pancreatic cytokine expression; and myeloperoxidase activity
      were decreased. In addition, treatment with melittin inhibited the activation of
      c-Jun NH(2)-terminal protein kinase (JNK) in the pancreas during cerulein-induced
      pancreatitis. In accordance with the results of in vivo experiments, melittin
      reduced cerulein-induced cell death, and production of inflammatory cytokines. In
      conclusion, our results suggest that melittin attenuated AP and AP-associated
      lung injury through the inhibition of JNK activation.

PMID- 21939784
TI  - Morphological and biochemical studies on aging and autophagy.
AB  - To maintain health in the elderly is a crucial objective for modern medicine that
      involves both basic and clinical researches. Autophagy is a fundamental auto
      cannibalizing process that preserves cellular homeostasis and, if altered, either
      by excess or defect, greatly changes cell fate and can result in incapacitating
      human diseases. Efficient autophagy may prolong lifespan, but unfortunately this
      process becomes less efficient with age. The present review is focused on the
      close relationship between autophagy and age-related disorders in different
      tissues/organs and in transgenic animal models. In particular, it comments on the
      up to date literature on mechanisms responsible for age-related impairment of
      autophagy. Moreover, before discussing about these mechanisms, it is necessary to
      describe the metabolic autophagic regulation of autophagy and the proteins
      involved in this process. At the end, these data would summarize the autophagic
      link with aging process, as important tools in the future biogerontology
      scenario.

PMID- 21939785
TI  - Extra-articular manifestations of rheumatoid arthritis: An update.
AB  - Rheumatoid arthritis (RA) is an immune-mediated disease involving chronic low
      grade inflammation that may progressively lead to joint destruction, deformity,
      disability and even death. Despite its predominant osteoarticular and
      periarticular manifestations, RA is a systemic disease often associated with
      cutaneous and organ-specific extra-articular manifestations (EAM). Despite the
      fact that EAM have been studied in numerous RA cohorts, there is no uniformity in
      their definition or classification. This paper reviews current knowledge about
      EAM in terms of frequency, clinical aspects and current therapeutic approaches.
      In an initial attempt at a classification, we separated EAM from RA co
      morbidities and from general, constitutional manifestations of systemic
      inflammation. Moreover, we distinguished EAM into cutaneous and visceral forms,
      both severe and not severe. In aggregated data from 12 large RA cohorts, patients
      with EAM, especially the severe forms, were found to have greater co-morbidity
      and mortality than patients without EAM. Understanding the complexity of EAM and
      their management remains a challenge for clinicians, especially since the
      effectiveness of drug therapy on EAM has not been systematically evaluated in
      randomized clinical trials.

PMID- 21939786
TI  - Respiratory, cerebrovascular and cardiovascular responses to isocapnic hypoxia.
AB  - We simultaneously measured respiratory, cerebrovascular and cardiovascular
      responses to 10-min of isoxic hypoxia at three constant CO(2) tensions in 15
      subjects. We observed four response patterns, some novel, for ventilation, middle
      cerebral artery blood flow velocity, heart rate and mean arterial blood pressure.
      The occurrence of the response patterns was correlated between some measures.
      Isoxic hyperoxic and hypoxic ventilatory sensitivities to CO(2) derived from
      these responses were equivalent to those measured with modified (Duffin)
      rebreathing tests, but cerebrovascular sensitivities were not. We suggest the
      different ventilatory response patterns reflect the time course of carotid body
      afferent activity; in some individuals, carotid body function changes during
      hypoxia in more complex ways than previously thought. We concluded that isoxic
      hyperoxic and hypoxic ventilatory sensitivities to CO(2) can be measured using
      multiple hypoxic ventilatory response tests only if care is taken choosing the
      isocapnic CO(2) levels used, but a similar approach to measuring the
      cerebrovascular response to isocapnic hyperoxia and hypoxia is unfeasible.

PMID- 21939787
TI  - Coupling of dyspnea perception and tachypneic breathing during hypercapnia.
AB  - Respiratory rhythm is susceptible to behavioral influences including emotions.
      Since laboratory dyspnea induces negative emotions, we examined whether
      tachypneic breathing occurs in relation to perception of dyspnea during CO(2)
      rebreathing (n=21). Dyspnea intensity scored by a visual analog scale and
      respiratory frequency started to increase rapidly once the intensity of the
      stimuli exceeded a threshold for the end-tidal CO(2) fraction. The thresholds for
      dyspnea and respiratory frequency were similar (7.5+/-0.1% and 7.6+/-0.2% of the
      end-tidal CO(2) fraction, respectively), while the threshold for tidal volume
      (8.0+/-0.2%), when the tidal volume had stabilized, was significantly higher than
      the thresholds for dyspnea (p<0.01) and respiratory frequency (p<0.05). A
      positive correlation was found between the thresholds for dyspnea and respiratory
      frequency (r=0.81, p<0.001), and these thresholds showed good agreement on a
      Bland-Altman plot. These findings suggest that the start of tachypneic breathing
      is coupled with the threshold for dyspnea.

PMID- 21939788
TI  - A 'Good' muscle in a 'Bad' environment: the importance of airway smooth muscle
      force adaptation to airway hyperresponsiveness.
AB  - Asthma is characterized by airway inflammation, with a consequent increase in
      spasmogens, and exaggerated airway narrowing in response to stimuli, termed
      airway hyperresponsiveness (AHR). The nature of any relationship between
      inflammation and AHR is less clear. Recent ex vivo data has suggested a novel
      mechanism by which inflammation may lead to AHR, in which increased basal ASM
      tone, due to the presence of spasmogens in the airways, may "strengthen" the ASM
      and ultimately lead to exaggerated airway narrowing. This phenomenon was termed
      "force adaptation" [Bosse, Y., Chin, L.Y., Pare, P.D., Seow, C.Y., 2009.
      Adaptation of airway smooth muscle to basal tone: relevance to airway
      hyperresponsiveness. Am. J. Respir. Cell Mol. Biol. 40, 13-18]. However, it is
      unknown whether the magnitude of the effect of force adaptation ex vivo could
      contribute to exaggerated airway narrowing in vivo. Our aim was to utilize a
      computational model of ASM shortening in order to quantify the potential effect
      of force adaptation on airway narrowing when all other mechanical factors were
      kept constant. The shortening in the model is dictated by a balance between
      physiological loads and ASM force-generating capacity at different lengths. The
      results suggest that the magnitude of the effect of force adaptation on ASM
      shortening would lead to substantially more airway narrowing during bronchial
      challenge at any given airway generation. We speculate that the increased basal
      ASM-tone in asthma, due to the presence of inflammation-derived spasmogens,
      produces an increase in the force-generating capacity of ASM, predisposing to AHR
      during subsequent challenge.

PMID- 21939789
TI  - Human inter-alpha-inhibitor is a substrate for factor XIIIa and tissue
      transglutaminase.
AB  - In this study, we show that inter-alpha-inhibitor is a substrate for both factor
      XIIIa and tissue transglutaminase. These enzymes catalyze the incorporation of
      dansylcadaverine and biotin-pentylamine, revealing that inter-alpha-inhibitor
      contains reactive Gln residues within all three subunits. These findings suggest
      that transglutaminases catalyze the covalent conjugation of inter-alpha-inhibitor
      to other proteins. This was demonstrated by the cross-linking between inter-alpha
      inhibitor and fibrinogen by either factor XIIIa or tissue transglutaminase.
      Finally, using quantitative mass spectrometry, we show that inter-alpha-inhibitor
      is cross-linked to the fibrin clot in a 1:20 ratio relative to the known factor
      XIIIa substrate alpha2-antiplasmin. This interaction may protect fibrin or other
      Lys-donating proteins from adventitious proteolysis by increasing the local
      concentration of bikunin. In addition, the reaction may influence the TSG-6/heavy
      Chain 2-mediated transfer of heavy chains observed during inflammation.

PMID- 21939790
TI  - WITHDRAWN: Association of Surgeons in Training Conference - Sheffield 2011.
AB  - The Publisher regrets that this article is an accidental duplication of an
      article that has already been published, doi:10.1016/j.ijsu.2011.09.003. The
      duplicate article has therefore been withdrawn.

PMID- 21939792
TI  - Challenges and opportunities in the management of the Hispanic/Latino patient
      with type 2 diabetes mellitus. Introduction.

PMID- 21939791
TI  - Short-term physical activity intervention decreases femoral bone marrow adipose
      tissue in young children: a pilot study.
AB  - Mechanical stimulation is necessary for maximization of geometrical properties of
      bone mineralization contributing to long-term strength. The amount of
      mineralization in bones has been reciprocally related to volume of bone marrow
      adipose tissue and this relationship is suggested to be an independent predictor
      of fracture. Physical activity represents an extrinsic factor that impacts both
      mineralization and marrow volume exerting permissive capacity of the growing
      skeleton to achieve its full genetic potential. Because geometry- and shape
      determining processes primarily manifest during the linear growth period, the
      accelerated structural changes accompanying early childhood (ages 3 to 6 y) may
      have profound impact on lifelong bone health. The objective of this pilot study
      was to determine if a short-term physical activity intervention in young children
      would result in augmentation of geometric properties of bone. Three days per week
      the intervention group (n=10) participated in 30 min of moderate intensity
      physical activity, such as jumping, hopping and running, and stretching
      activities, whereas controls (n=10) underwent usual activities during the 10-week
      intervention period. Femoral bone marrow adipose tissue volume and total body
      composition were assessed by magnetic resonance imaging and dual-energy X-ray
      absorptiometry, respectively, at baseline and after 10 weeks. Although after 10
      weeks, intergroup differences were not observed, a significant decrease in
      femoral marrow adipose tissue volume was observed in those participating in
      physical activity intervention. Our findings suggest that physical activity may
      improve bone quality via antagonistic effects on femoral bone marrow adipose
      tissue and possibly long-term agonistic effects on bone mineralization.

PMID- 21939793
TI  - Understanding the Hispanic/Latino patient.
AB  - The Hispanic/Latino population is the largest minority group in the United
      States, representing approximately 16% of the population in 2010. The US Census
      Bureau defines Hispanic/Latino origin as ethnicity, which tends to be associated
      with culture and is distinct from race. Based on the US Census Bureau
      classifications, Hispanics/Latinos have at least 3 main racial backgrounds
      (white, black, and Native Indian), with the combination and proportion differing
      among Hispanic/Latino subgroups. The reflection of these racial differences in
      genetic ancestry partly explains why biological characteristics differ among
      Hispanic/Latino subgroups. Partly as a result of variations in biological
      characteristics, the risk of type 2 diabetes mellitus varies among
      Hispanic/Latino subgroups. According to data from the 1982 to 1984 Hispanic
      Health and Nutrition Examination Survey (HHANES), the prevalence of diagnosed and
      undiagnosed type 2 diabetes among adults aged 45 to 74 years was higher in
      Mexican Americans (23.9%) and Puerto Ricans (26.1%) compared with Cubans (15.8%).
      In addition to genetics, there are multiple social and cultural factors that
      affect the prevalence and course of type 2 diabetes in Hispanic/Latino
      individuals. Although certain aspects of Hispanic/Latino culture may become
      barriers in the management of type 2 diabetes in this population, these cultural
      characteristics may also represent an opportunity for prevention and/or
      improvement of care. It is important for healthcare providers to have an
      understanding and appreciation of Hispanic/Latino culture in order to provide
      their Hispanic/Latino patients with healthcare that is culturally and socially
      appropriate. Only by considering genetic, social, and cultural factors can type 2
      diabetes be successfully prevented, treated, and managed in Hispanic/Latino
      patients.

PMID- 21939794
TI  - Improving treatment in Hispanic/Latino patients.
AB  - The prevalence of type 2 diabetes mellitus is higher in Hispanic/Latino
      individuals living in the United States compared with their non-Hispanic white
      counterparts. Many factors contribute to the increased prevalence of type 2
      diabetes, including biological characteristics, socioeconomic conditions, and
      cultural aspects. The contribution of genetics to the risk of type 2 diabetes in
      Hispanic/Latino patients is becoming increasingly clear, but this inherent risk
      factor cannot be modified. However, certain socioeconomic and cultural factors,
      such as reduced access to healthcare, language barriers, cultural beliefs, and
      lack of cultural competence by the healthcare provider, are modifiable and should
      be overcome in order to improve the management of type 2 diabetes in
      Hispanic/Latino patients. At the healthcare system level, policies should be put
      into place to reduce disparities between Hispanics/Latinos and non-Hispanic
      whites regarding health insurance coverage and access to healthcare. At the
      healthcare provider and patient level, cultural beliefs should be taken into
      consideration when selecting adequate treatment. Overall, type 2 diabetes
      management should be individualized by identifying the preferred language and
      level of acculturation for each patient. These considerations are necessary to
      further improve communication through culturally appropriate educational
      materials and programs. These strategies may help to overcome the barriers in the
      treatment of type 2 diabetes in Hispanic/Latino patients.

PMID- 21939795
TI  - Unmet needs in Hispanic/Latino patients with type 2 diabetes mellitus.
AB  - In the United States, the prevalence of adults who are overweight or obese is
      higher in Hispanics/Latinos compared with non-Hispanic whites. In addition, data
      from the National Health and Nutrition Examination Survey (NHANES) indicate that
      the prevalence of type 2 diabetes mellitus is consistently greater in
      racial/ethnic minority groups, such as Hispanics/Latinos, compared with non
      Hispanic whites. In fact, data from the Centers for Disease Control and
      Prevention (CDC) from 2007 to 2009 suggest that the prevalence of type 2 diabetes
      is almost twice as high in Hispanics/Latinos compared with non-Hispanic whites
      (11.8% vs. 7.1%, respectively). Although genetics plays a role in the increased
      prevalence of type 2 diabetes in Hispanics/Latinos, cultural and environmental
      factors also contribute. In addition to the increased prevalence of type 2
      diabetes in Hispanics/Latinos, evidence suggests that the patients in this
      population are often undertreated and, therefore, less likely to achieve control
      of their glucose, blood pressure, and lipid levels. Because individuals with type
      2 diabetes have a 2- to 4-fold increased risk of cardiovascular disease compared
      with individuals with normal glucose levels, there is consensus that targeting
      environmental factors, particularly the development of obesity at an early age,
      is the most cost-effective approach to prevent the development of type 2 diabetes
      and its broad spectrum of complications, including cardiovascular disease.
      Cultural and socioeconomic barriers, such as language, cost, and access to goods
      and services, must be overcome to improve management of type 2 diabetes in this
      high-risk population. By increasing healthcare provider awareness and the
      availability of programs tailored to Hispanic/Latino individuals, the current
      treatment gap among ethnic minorities in the United States will progressively
      narrow, and eventually, disappear.

PMID- 21939796
TI  - Intramedullary nailing in fracture treatment: history, science and Kuntscher's
      revolutionary influence in Vienna, Austria.
AB  - Although the first intermedullary fixation technique was already reported in
      1886, successfully inter-medullary nailing did not start until November 1939 when
      Kuntscher's revolutionary technique was applied for the first time. Whereas
      Kuntscher initially stated that his "marrow nail" was suitable for almost every
      fracture type as well as for other procedures including fixation of osteotomies,
      joint arthrodesis and pseudarthro-sis treatment he tried to develop an own nail
      for every possible fracture type through the years. Undoubtedly, Kuntscher has to
      be considered one of the most influential surgeons. Nevertheless, he was never
      offered a university position and a lot of people did not acknowledge his
      brilliancy until his death in 1972. Only in Vienna the willingness to seize
      Kuntscher's ideas was high. Therefore, in addition to a historic overview and to
      fundamental knowledge referring to reamed and unreamed respectively to static and
      dynamic nailing Kuntscher's influence on Viennese researchers is presented in our
      paper.

PMID- 21939797
TI  - Treatment of acute tibial shaft fractures with an expandable nailing system: a
      systematic review of the literature.
AB  - Locked Intramedullary Nailing is an established method of treatment for tibial
      shaft fractures. Locking of tibial nails is however not without its drawbacks.
      Locking is time consuming, and is associated with a noteworthy complication rate.
      The Fixion IM nailing system is an expandable nail designed to eliminate some of
      these drawbacks. We have performed a systematic review of the literature to
      determine the safety and efficacy of this system. Publications examining the use
      of the Fixion system were identified from the MEDLINE and the Cochrane databases.
      Forty-one citations were generated by the MEDLINE search. Of these, two quasi
      randomised trials and eight case series satisfied our selection criteria and were
      reviewed. Overall the average reoperation rate for the Fixion nail was 10.2%.
      Shortening occurred in 3% of cases and fracture propagation was reported in 2% of
      cases. The Fixion cohort united at an average of 12.2 weeks and the average
      operative time was 54 minutes. The Fixion system eliminated complications and
      reoperations associated with the use of locking screws. Further studies in the
      form of randomised controlled trials are needed to evaluate the Fixion system
      against conventional locked nails.

PMID- 21939798
TI  - Reamed versus minimally reamed nailing: a prospectively randomised study of 100
      patients with closed fractures of the tibia.
AB  - It is generally accepted that in tibial fractures the results of reamed
      intramedullary nailing are better than those of unreamed. However, it is not
      known whether the clinical effects of reaming are cumulative or if minimal
      reaming would induce the same beneficial effects as more extensive reaming. This
      international multicentre study has investigated the effects of different degrees
      of reaming. 100 patients with closed diaphyseal tibial fractures were
      prospectively randomised in two centres. Method of treatment was reamed nailing
      up to 12 mm inserting an 11 mm tibial nail (n: 50), and minimally reamed nailing
      up to 10 mm inserting a 9 mm tibial nail (n: 50). All patients included in the
      study had follow-up studies at 4,8,12,16,26 and 52 weeks after trauma. Sixty-six
      male and thirty-four female patients with an average age of 37.5 years were
      included in the study. Gender, age, and injury side were identical in both
      groups. There was no significant difference of complications in the two methods.
      The rate of deep wound infections was higher in the reamed group (n: 3) versus
      the minimally reamed group (n: 1). Union occurred earlier in the reamed group (17
      wks) compared to patients with minimally reamed nailing (19 wks), and there were
      more patients with reamed nails in whom the fracture had healed by 16 weeks (57%)
      versus the minimally reamed group (43%), however, this was not statistically
      significant. Pain scales were similar for both groups from week 4 to week 52. A
      considerable number of outcome parameters including knee and ankle function, as
      well as the comparison of time intervals to restart certain activities, and
      return to work showed no significant statistical difference between the two
      groups. However, patients of the extensive reamed group returned earlier to
      running, training, and normal sports activities. This study found no significant
      evidence that more extensive reaming gave better results, however there seemed to
      be a tendency of more aggressive reaming to induce earlier fracture healing with
      a tendency of faster recovery times.

PMID- 21939799
TI  - Clinical results of trochanteric fractures treated with the TARGON(r) proximal
      femur intramedullary nailing fixation system.
AB  - The aim of this study was to investigate the outcome of 352 (71 males) patients
      with trochanteric fractures that were treated with the TARGON(r) PF nail. The
      mean age was 83 years. According to the Jensen classification, there were 35
      cases in type 1,94 cases in type 2,75 in type 3,63 in type 4 and 85 in type 5.
      Postoperative all patients were allowed to fully weight bear from the first
      postoperative day. Clinical and radiological data were collected at regular time
      intervals. The average waiting time to surgical reconstruction for the 352 cases
      was 3.5 days (1-7). The mean length of hospital stay was 14 days (5-22). The
      operative times ranged from 11 to 125 minutes with an average time of 32 minutes.
      Fifty percent of the patients regained their mobility to their pre-injury level
      at the final follow up. Out of 310 patients (88%) who were available for
      radiographie assessment, all fractures united except one case. 300 (85%) of the
      lag screws were placed in the inferior area in the anteroposterior view and in
      the central area in the lateral view (IM), which is regarded as the optimal
      position. The lag screws back-slided between 0 and 19 mms with an average of 6
      mm. Sliding distance of the lag screw for over 10 mm was seen in 42 cases (13%).
      Varus collapse of the femoral head-and-neck greater than 10 degrees  was observed
      in 6 cases. Postoperative complications developed in 6 cases (1.7%), including
      wound infection in two cases, and secondary fracture at the subtrochanteric
      region, nonunion, back-out of the guiding sleeve and medial perforation of the
      lag screw, each in one case. The presented case series indicates that the
      TARGON(r) PF system is an effective and safe internal fixation device for
      trochanteric proximal femoral fractures. Further, prospective comparative
      evidence regarding the use of this system is needed to analyse and validate the
      presented clinical impression of our centre.

PMID- 21939800
TI  - Reaming Irrigator Aspirator system: early experience of its multipurpose use.
AB  - The evolution of contemporary intramedullary reaming systems has recently
      generated the Reamer Irrigator Aspirator system (RIA-Synthes(r)), which has
      progressively gained in popularity as well as in indications. The preliminary
      results of its use over the initial period of 18 months ata single tertiary
      referral centre were prospectively collected and are presented. The wide spectrum
      of RIA's indications have been exploited, including 7 patients with polytrauma
      that underwent acute femoral nailing, 8 with femoral intramedullary
      osteomyelitis, 9 with pathological lesions of the femoral shaft, as well as 18
      patients where the RIA system has been used to harvest morselised autologous bone
      graft in the presence of recalcitrant atrophie non-unions and bone defects.
      Overall its use was proven safe and efficient, achieving aggressive medullary
      canal debridement, collection of adequate samples for further analysis in the
      infected and oncology cases, as well as impressive volumes of the osteoinductive
      and osteogenic reaming debris for grafting purposes. No pulmonary complications
      or evidence of the second hit sequelae were recorded in the polytrauma patient
      subgroup despite the presence of a high ISS Further controlled clinical studies
      should follow focused in all different applications of this reliable, user
      friendly and impressively versatile system, to validate these preliminary
      results.

PMID- 21939801
TI  - Does the location of the entry point affect the reduction of proximal humeral
      fractures? A cadaveric study.
AB  - The selection of the correct entry point for stabilisation of long bone fractures
      and particularly of the humerus with intramedullary nailing is of paramount
      importance. The insertion of a nail from the correct entry point ensures
      anatomical alignment of the head and the shaft fragment. However, particularly
      for the humerus, the literature addressing this issue is obscure. Twenty
      cadaveric humeri without soft tissue attachment were studied. Two groups were
      studied: Group A (straight nail) and Group B (angled nail). A fracture of the
      surgical neck of the humerus was simulated. Then intramedullary nail was inserted
      through the correct entry hole. Displacement at the fracture site and force to
      reduce the displacement were measured. The average horizontal displacement was
      2.5 +/- 2.2 mm in Group A and 1.9 +/- 1.1 mm in Group B. The humeral shaft tended
      to displace medially. The force required to reduce the produced displacement was
      usually less than 15 N. Anatomical reduction could not be obtained in 3/20 humeri
      even after applying a force of over 35 N. Our results of an average displacement
      of 2 mm following nail insertion, supports the significance of the entry point as
      a cause of loss of reduction at the fracture site post nail insertion. In most
      cases, anatomical reduction can be corrected with relative small forces, whereas
      in the rest the correction of the displacement is not feasible even with the
      application of substantial forces.

PMID- 21939802
TI  - Impact of guideline implementation by a fracture nurse on subsequent fractures
      and mortality in patients presenting with non-vertebral fractures.
AB  - INTRODUCTION: Systematic implementation of guidelines in patients presenting with
      a fracture increases identification of patients at high risk for subsequent
      fractures and contributes to a decreased fracture risk. Its effect on prevention
      of subsequent fractures and on mortality has not been documented. The aim of this
      study was to determine the impact of the implementation of specific guidelines on
      the risk of subsequent fractures and mortality in patients presenting with a non
      vertebral fracture (NVF). PATIENTS AND METHODS: Before-after impact analysis in
      consecutive patients older than 50 years who were admitted to the hospital with a
      NVF during 2 periods: pre-intervention group (n = 1,920, enrolled in 1999-2001)
      and intervention group (n = 1,335, enrolled in 2004-2006). The intervention
      consisted of a dedicated fracture nurse who systematically offered fracture risk
      evaluation and treatment according to available guidelines. The 2-year absolute
      risk (AR) and hazard ratio's (HR, with 95% confidence interval (CI)) of
      subsequent NVFs and mortality were analysed between both groups after adjustment
      for age, sex and baseline fracture location by multivariable Cox regression and
      by intention-to-treat. RESULTS: The AR of subsequent fracture was 9.9% before and
      6.7% after intervention, indicating a decrease of 35% in the risk of subsequent
      fracture (HR 0.65; CI: 0.51-0.84, after adjustment for age, sex and baseline
      fracture location) and 17.9% and 11.6%, respectively, for subsequent mortality,
      indicating a decrease of 33% in the risk of subsequent mortality (HR: 0.67; CI:
      0.55-0.81, after adjustment for age, sex and baseline fracture location).
      CONCLUSIONS: Systematic implementation of guidelines for fracture prevention by a
      dedicated fracture nurse immediately after a NVF is associated with a significant
      reduction of the 2-year risk of subsequent NVF and mortality.

PMID- 21939803
TI  - The Kuntscher Society: the South American perspective.
AB  - This paper reviews the beginning of the South American Council of the Kuntscher
      International Society, a group of enthusiastic South American Orthopaedic
      Surgeons committed to teach the principles and advances of intramedullary nailing
      technique in this part of the world. The goals, current and future educational
      activities are highlighted.

PMID- 21939804
TI  - Cerebral fat emboli: a trigger of post-operative delirium.
AB  - Accumulating evidence implicates cerebral fat embolism (CFE) as a causative agent
      in post-operative confusion (POC). CFE occurs following orthopaedic procedures
      including, intra-medullary (IM) nailing and total joint arthroplasty (TJA). The
      incidence of CFE is high (59-100% TJA) and the resulting POC is associated with
      higher overall complication rates. Cognitive dysfunction improves in many
      patients but can persist - with potentially disastrous outcomes. The
      pathomechanics of CFE implicate circulating lipid micro-emboli (LME) that are
      forced from IM depots by instrumentation/nailing. Passage to the left side of the
      heart is possible through intra-cardiac or arteriovenous shunts in the lung. LME
      are propelled to the brain where they cause disruption via ischemia or by
      alterations in the blood-brain-barrier - causing cerebral oedema. Prevention of
      CFE follows established practices for preventing FES and consideration of
      additional techniques to remove resident fat and reduce IM pressures. When CFE
      occurs supportive treatment should be established.

PMID- 21939805
TI  - Importance of adherence and the role of nonfinancial barriers.

PMID- 21939806
TI  - Bisphosphonate-related osteonecrosis of the jaws associated with photodynamic
      therapy.

PMID- 21939807
TI  - Beware the idle title.

PMID- 21939808
TI  - TCR or not TCR?

PMID- 21939809
TI  - Familiarity does not breed competence.

PMID- 21939811
TI  - Is tramadol better than fentanyl for conscious sedation?

PMID- 21939813
TI  - Facelift approach in benign parotid surgery, Frey syndrome, and total superficial
      parotidectomy.

PMID- 21939814
TI  - Arthroscopic lysis and lavage versus operative arthroscopy in the outcome of
      temporomandibular joint internal derangement: a comparative study based on Wilkes
      stages.
AB  - PURPOSE: To assess whether arthroscopic lysis and lavage (ALL) or operative
      arthroscopy (OA) is more effective for the treatment of temporomandibular joint
      (TMJ) internal derangement at any stage of involvement. PATIENTS AND METHODS: In
      458 patients (611 joints) with internal derangement of the TMJ classified as
      Wilkes stages II through V, arthroscopy was performed. Pain (visual analog scale
      score, 0-100) and maximal interincisal opening were assessed at 1, 3, 6, 9, 12,
      and 24 months after surgery. RESULTS: ALL was performed in 308 of 611
      arthroscopies (50.4%), and OA was performed in 303 arthroscopies (49.59%). A
      significant decrease in pain (P < .001) was observed for all patients at any time
      during the follow-up period from the first month postoperatively to the end of
      the 2-year follow-up period. A highly significant increase in mouth opening
      greater than 13 mm was observed in the group of patients classified as Wilkes
      stage IV from the first month postoperatively. When we compared ALL versus OA
      among Wilkes stages, no significant differences in terms of pain were observed
      during the entire follow-up period. CONCLUSIONS: Both ALL and OA are equally
      effective at decreasing pain in patients with TMJ internal derangement of any
      Wilkes stage. Patients classified as Wilkes stage IV presenting with chronic
      closed lock of the TMJ had the highest decrease in pain and the highest increase
      in mouth opening among the stages, thus confirming these patients as the best
      candidates for arthroscopy.

PMID- 21939815
TI  - Prostate development and growth in benign prostatic hyperplasia.
AB  - The etiology of benign prostatic hyperplasia [BPH] in elderly men has intrigued
      anatomists, pathologists and scientists for centuries. Studies of morbid anatomy,
      clinical observations and contemporary cellular biology have contributed to an
      evolving interpretation of the causality of the disease. Insights into the
      detailed microanatomy and ductal architecture of the prostate during stages of
      fetal and early postnatal development suggest that mechanisms involved in the
      early growth period become aberrantly expressed in elderly men. Age, hormones and
      epithelial-mesenchymal interactions are all contributing factors to the
      pathogenesis of BPH. Control of the microenvironment in normal and abnormal
      growth is a multifactorial process. Susceptibility to the disease may include
      clinical comorbid diseases, region-specific changes in cell-cell interactions and
      a variety of signaling pathways including a novel hypothesis regarding the role
      of the primary cilium as a regulator of signal transduction mechanisms. Recent
      work in animal models has shown that there are region-specific differences within
      the prostate that may be significant because of the dynamic and intricate
      interplay between the epithelium and mesenchyme. Because of the focal nature of
      BPH a closer examination of normal morphogenesis patterns, which defines the
      gland's architecture, may facilitate a detailed understanding of the atypical
      growth patterns.

PMID- 21939816
TI  - Beyond the boundaries-endometriosis: typical and atypical locations.
AB  - Endometriosis is characterized by the presence of endometrial glands and stroma
      in an ectopic location outside the endometrial cavity. This condition affects
      women during their reproductive years. Ovaries are by far the commonest location
      of endometriosis and have peculiar imaging features. However, the imaging
      diagnosis of extraovarian endometriosis is difficult to make both clinically and
      radiologically. The purpose of this article is to review the imaging features of
      endometriosis at typical and atypical sites on different modalities and to
      describe the commonly encountered complications. Atypical sites for endometriosis
      include the gastrointestinal tract, urinary tract, soft tissues, and chest.
      Depending on the site, they can present with varied symptoms, including bowel
      obstruction, melena, hematuria, dysuria, dyspnea, and swelling in the soft
      tissues, respectively. The endometriotic implant in the extraovarian location is
      a challenging diagnosis. It is important to be aware of the sites, radiologic
      appearances, and complications of ovarian and extraovarian endometriosis while
      evaluating a woman in the reproductive age group with appropriate symptomatology.
      Endometriosis at extraovarian locations is a challenging diagnosis clinically and
      radiologically. Clinical symptomatology with characteristic imaging features in
      the appropriate patient population is helpful in reaching the diagnosis. Precise
      diagnosis regarding presence, location, and extent of endometriosis is useful for
      preoperative evaluation and surgical planning of endometriosis.

PMID- 21939817
TI  - Vascular anomalies: what they are, how to diagnose them, and how to treat them.
AB  - Vascular anomalies are congenital lesions that most often first present in
      pediatric patients. Treatment of these lesions is a multidisciplinary team
      approach, involving several specialties, including diagnostic and interventional
      radiology, dermatology, general and plastic surgery, otolaryngology, and
      hematology. Knowing the characteristic findings of vascular anomalies on
      ultrasound, computed tomography, and magnetic resonance imaging leads to early,
      accurate diagnosis and therapeutic intervention of these lesions. This article
      discusses the gross and radiographic appearances and the latest treatment options
      for vascular anomalies.

PMID- 21939818
TI  - Current update on primary and secondary sclerosing cholangitis.
AB  - Sclerosing cholangitis can be idiopathic (primary) or secondary to an
      identifiable cause. Irrespective of cause, sclerosing cholangitis usually
      progresses to end-stage liver disease and warrants orthotopic liver
      transplantation. Recent studies provide new insights into the etiopathogenesis,
      natural history, diagnosis, and management of these different entities.

PMID- 21939820
TI  - Exercise-induced left atrial compression by a hiatus hernia.

PMID- 21939819
TI  - Noninvasive coronary imaging for atherosclerosis in human immunodeficiency virus
      infection.
AB  - Coronary artery disease is increasingly recognized as an important contributor to
      morbidity and mortality among persons living with human immunodeficiency virus
      (HIV) infection. Traditional cardiovascular disease risk factors as well as
      aspects of HIV infection and its therapy contribute to the increased coronary
      artery disease observed in HIV. Advances in noninvasive imaging methodologies in
      both computed tomography and magnetic resonance imaging provide opportunities to
      evaluate coronary artery atherosclerosis in ways not possible by conventional
      invasive x-ray angiography. Application of these techniques may prove very useful
      in the study of atherosclerosis in many diseases, such as HIV.

PMID- 21939821
TI  - Echocardiographic assessment of myocardial strain.
AB  - Echocardiographic strain imaging, also known as deformation imaging, has been
      developed as a means to objectively quantify regional myocardial function. First
      introduced as post-processing of tissue Doppler imaging velocity converted to
      strain and strain rate, strain imaging has more recently also been derived from
      digital speckle tracking analysis. Strain imaging has been used to gain greater
      understanding into the pathophysiology of cardiac ischemia and infarction,
      primary diseases of the myocardium, and the effects of valvular disease on
      myocardial function, and to advance our understanding of diastolic function.
      Strain imaging has also been used to quantify abnormalities in the timing of
      mechanical activation for heart failure patients undergoing cardiac
      resynchronization pacing therapy. Further advances, such as 3-dimensional speckle
      tracking strain imaging, have emerged to provide even greater insight. Strain
      imaging has become established as a robust research tool and has great potential
      to play many roles in routine clinical practice to advance the care of the
      cardiovascular patient. This perspective reviews the physiology of myocardial
      strain, the technical features of strain imaging using tissue Doppler imaging and
      speckle tracking, their strengths and weaknesses, and the state-of-the-art
      present and potential future clinical applications.

PMID- 21939822
TI  - The CT-STAT (Coronary Computed Tomographic Angiography for Systematic Triage of
      Acute Chest Pain Patients to Treatment) trial.
AB  - OBJECTIVES: The purpose of this study was to compare the efficiency, cost, and
      safety of a diagnostic strategy employing early coronary computed tomographic
      angiography (CCTA) to a strategy employing rest-stress myocardial perfusion
      imaging (MPI) in the evaluation of acute low-risk chest pain. BACKGROUND: In the
      United States, >8 million patients require emergency department evaluation for
      acute chest pain annually at an estimated diagnostic cost of >$10 billion.
      METHODS: This multicenter, randomized clinical trial in 16 emergency departments
      ran between June 2007 and November 2008. Patients were randomly allocated to CCTA
      (n = 361) or MPI (n = 338) as the index noninvasive test. The primary outcome was
      time to diagnosis; the secondary outcomes were emergency department costs of care
      and safety, defined as freedom from major adverse cardiac events in patients with
      normal index tests, including 6-month follow-up. RESULTS: The CCTA resulted in a
      54% reduction in time to diagnosis compared with MPI (median 2.9 h [25th to 75th
      percentile: 2.1 to 4.0 h] vs. 6.3 h [25th to 75th percentile: 4.2 to 19.0 h], p <
      0.0001). Costs of care were 38% lower compared with standard (median $2,137 [25th
      to 75th percentile: $1,660 to $3,077] vs. $3,458 [25th to 75th percentile: $2,900
      to $4,297], p < 0.0001). The diagnostic strategies had no difference in major
      adverse cardiac events after normal index testing (0.8% in the CCTA arm vs. 0.4%
      in the MPI arm, p = 0.29). CONCLUSIONS: In emergency department acute, low-risk
      chest pain patients, the use of CCTA results in more rapid and cost-efficient
      safe diagnosis than rest-stress MPI. Further studies comparing CCTA to other
      diagnostic strategies are needed to optimize evaluation of specific patient
      subsets. (Coronary Computed Tomographic Angiography for Systematic Triage of
      Acute Chest Pain Patients to Treatment [CT-STAT]; NCT00468325).

PMID- 21939823
TI  - Coronary angiographic evaluation of low-risk chest pain in the emergency
      department CT-STAT, or maybe not quite that fast?

PMID- 21939824
TI  - Percutaneous coronary intervention versus coronary artery bypass graft surgery in
      left main coronary artery disease: a meta-analysis of randomized clinical data.
AB  - OBJECTIVES: The purpose of this study was to determine the safety and efficacy of
      percutaneous coronary intervention (PCI) compared with coronary artery bypass
      graft (CABG) in patients with left main coronary artery (LMCA) disease.
      BACKGROUND: Previous meta-analyses of PCI versus CABG in LMCA disease mainly
      included nonprospective, observational studies. Several new randomized trials
      have recently been reported. METHODS: We identified 1,611 patients from 4
      randomized clinical trials for the present meta-analysis. The primary endpoint
      was the 1-year incidence of major adverse cardiac and cerebrovascular events
      (MACCE), defined as death, myocardial infarction (MI), target vessel
      revascularization (TVR), or stroke. RESULTS: PCI was associated with a
      nonsignificantly higher 1-year rate of MACCE compared with CABG (14.5% vs. 11.8%;
      odds ratio [OR]: 1.28; 95% confidence interval [CI]: 0.95 to 1.72; p = 0.11),
      driven by increased TVR (11.4% vs. 5.4%; OR: 2.25; 95% CI: 1.54 to 3.29; p <
      0.001). Conversely, stroke occurred less frequently with PCI (0.1% vs. 1.7%; OR:
      0.15; 95% CI: 0.03 to 0.67; p = 0.013). There were no significant differences in
      death (3.0% vs. 4.1%; OR: 0.74; 95% CI: 0.43 to 1.29; p = 0.29) or MI (2.8% vs.
      2.9%; OR: 0.98; 95% CI: 0.54 to 1.78; p = 0.95). CONCLUSIONS: In patients with
      LMCA disease, PCI was associated with nonsignificantly different 1-year rates of
      MACCE, death, and MI, a lower risk of stroke, and a higher risk of TVR compared
      with CABG.

PMID- 21939826
TI  - Vitamin D and cardiovascular disease: time for large randomized trials.

PMID- 21939825
TI  - Vitamin D, parathyroid hormone, and cardiovascular events among older adults.
AB  - OBJECTIVES: The aim of this study was to evaluate associations of 25
      hydroxyvitamin D (25-OHD) and parathyroid hormone (PTH) concentrations separately
      and in combination with incident cardiovascular events and mortality during 14
      years of follow-up in the CHS (Cardiovascular Health Study). BACKGROUND: Vitamin
      D deficiency and PTH excess are common in older adults and may adversely affect
      cardiovascular health. METHODS: A total of 2,312 participants who were free of
      cardiovascular disease at baseline were studied. Vitamin D and intact PTH were
      measured from previously frozen serum using mass spectrometry and a 2-site
      immunoassay. Outcomes were adjudicated cases of myocardial infarction, heart
      failure, cardiovascular death, and all-cause mortality. RESULTS: There were 384
      participants (17%) with serum 25-OHD concentrations <15 ng/ml and 570 (25%) with
      serum PTH concentrations >= 65 pg/ml. After adjustment, each 10 ng/ml lower 25
      OHD concentration was associated with a 9% greater (95% confidence interval [CI]:
      2% to 17% greater) relative hazard of mortality and a 25% greater (95% CI: 8% to
      44% greater) relative hazard of myocardial infarction. Serum 25-OHD
      concentrations <15 ng/ml were associated with a 29% greater (95% CI: 5% to 55%
      greater) risk for mortality. Serum PTH concentrations >= 65 pg/ml were associated
      with a 30% greater risk for heart failure (95% CI: 6% to 61% greater) but not
      other outcomes. There was no evidence of an interaction between serum 25-OHD and
      PTH concentrations and cardiovascular events. CONCLUSIONS: Among older adults, 25
      OHD deficiency is associated with myocardial infarction and mortality; PTH excess
      is associated with heart failure. Vitamin D and PTH might influence
      cardiovascular risk through divergent pathways.

PMID- 21939828
TI  - Cutaneous clopidogrel hypersensitivity: give steroids and do not stop the
      clopidogrel.

PMID- 21939827
TI  - Characterization of clopidogrel hypersensitivity reactions and management with
      oral steroids without clopidogrel discontinuation.
AB  - OBJECTIVES: The purpose of this study was to characterize clopidogrel
      hypersensitivity and describe its successful management with oral steroids
      without clopidogrel discontinuation. BACKGROUND: Hypersensitivity reactions to
      clopidogrel are poorly understood and present difficulty in management. METHODS:
      Patients diagnosed with clopidogrel hypersensitivity after percutaneous coronary
      intervention underwent evaluation and received oral prednisone without
      clopidogrel discontinuation. Cutaneous testing was performed after completion of
      clopidogrel therapy for diagnosis and assessment of cross-reactivity. RESULTS:
      Sixty-two patients representing 1.6% of the percutaneous coronary intervention
      population developed clopidogrel hypersensitivity during the study period. The
      mean age was 62 +/- 11 years, 71% of patients were male, and 35% reported prior
      adverse drug reaction. Clopidogrel hypersensitivity manifested as generalized
      exanthema in 79%, localized skin reaction in 16%, and angioedema or urticaria in
      5% of patients. Biopsy of affected areas demonstrated a lymphocyte-mediated
      delayed hypersensitivity reaction. Complete resolution of hypersensitivity
      reaction was observed in 61 patients (98%) with a short course of oral
      prednisone. Cutaneous testing confirmed delayed hypersensitivity reaction to
      clopidogrel in 34 (81%) and immediate hypersensitivity in 3 of 42 patients (7%)
      tested. Allergenic cross-reactivity was observed for ticlopidine in 10 (24%),
      prasugrel in 7 (17%), and both ticlopidine and prasugrel in 3 patients (7%).
      Histological examination showed lymphocyte-mediated hypersensitivity in abnormal
      patch test areas. CONCLUSIONS: Clopidogrel hypersensitivity is manifested as
      generalized exanthema and is caused by a lymphocyte-mediated delayed
      hypersensitivity in most patients. This can be managed with oral steroids without
      clopidogrel discontinuation. Allergenic cross-reactivity with ticlopidine,
      prasugrel, or both is present in a significant number of patients with
      clopidogrel hypersensitivity.

PMID- 21939829
TI  - Education, income, and incident heart failure in post-menopausal women: the
      Women's Health Initiative Hormone Therapy Trials.
AB  - OBJECTIVES: The purpose of this study is to estimate the effect of education and
      income on incident heart failure (HF) hospitalization among post-menopausal
      women. BACKGROUND: Investigations of socioeconomic status have focused on
      outcomes after HF diagnosis, not associations with incident HF. We used data from
      the Women's Health Initiative Hormone Trials to examine the association between
      socioeconomic status levels and incident HF hospitalization. METHODS: We included
      26,160 healthy, post-menopausal women. Education and income were self-reported.
      Analysis of variance, chi-square tests, and proportional hazards models were used
      for statistical analysis, with adjustment for demographics, comorbid conditions,
      behavioral factors, and hormone and dietary modification assignments. RESULTS:
      Women with household incomes <$20,000 a year had higher HF hospitalization
      incidence (57.3/10,000 person-years) than women with household incomes >$50,000 a
      year (16.7/10,000 person-years; p < 0.01). Women with less than a high school
      education had higher HF hospitalization incidence (51.2/10,000 person-years) than
      college graduates and above (25.5/10,000 person-years; p < 0.01). In
      multivariable analyses, women with the lowest income levels had 56% higher risk
      (hazard ratio: 1.56, 95% confidence interval: 1.19 to 2.04) than the highest
      income women; women with the least amount of education had 21% higher risk for
      incident HF hospitalization (hazard ratio: 1.21, 95% confidence interval: 0.90 to
      1.62) than the most educated women. CONCLUSIONS: Lower income is associated with
      an increased incidence of HF hospitalization among healthy, post-menopausal
      women, whereas multivariable adjustment attenuated the association of education
      with incident HF.

PMID- 21939830
TI  - Payment source, quality of care, and outcomes in patients hospitalized with heart
      failure.
AB  - OBJECTIVES: The aim of this study was to analyze the relationship between payment
      source and quality of care and outcomes in heart failure (HF). BACKGROUND: HF is
      a major cause of morbidity and mortality. There is a lack of studies assessing
      the association of payment source with HF quality of care and outcomes. METHODS:
      A total of 99,508 HF admissions from 244 sites between January 2005 and September
      2009 were analyzed. Patients were grouped on the basis of payer status
      (private/health maintenance organization, no insurance, Medicare, or Medicaid)
      with private/health maintenance organization as the reference group. RESULTS: The
      no-insurance group was less likely to receive evidence-based beta-blockers
      (adjusted odds ratio [OR]: 0.73; 95% confidence interval [CI]: 0.62 to 0.86),
      implantable cardioverter-defibrillator (OR: 0.59; 95% CI: 0.50 to 0.70), or
      anticoagulation for atrial fibrillation (OR: 0.73; 95% CI: 0.61 to 0.87).
      Similarly, the Medicaid group was less likely to receive evidence-based beta
      blockers (OR: 0.86; 95% CI: 0.78 to 0.95) or implantable cardioverter
      defibrillators (OR: 0.86; 95% CI: 0.78 to 0.96). Angiotensin-converting enzyme
      inhibitors or angiotensin receptor blockers and beta-blockers were prescribed
      less frequently in the Medicare group (OR: 0.89; 95% CI: 0.81 to 0.98). The
      Medicare, Medicaid, and no-insurance groups had longer hospital stays. Higher
      adjusted rates of in-hospital mortality were seen in patients with Medicaid (OR:
      1.22; 95% CI: 1.06 to 1.41) and in patients with reduced systolic function with
      no insurance. CONCLUSIONS: Decreased quality of care and outcomes for patients
      with HF were observed in the no-insurance, Medicaid, and Medicare groups compared
      with the private/health maintenance organization group.

PMID- 21939831
TI  - Despair over disparities: challenges and pathways to "affordable care".

PMID- 21939833
TI  - Atrial functional mitral regurgitation: the left atrium gets its due respect.

PMID- 21939832
TI  - Evidence of atrial functional mitral regurgitation due to atrial fibrillation:
      reversal with arrhythmia control.
AB  - OBJECTIVES: The purpose of this study was to determine whether atrial
      fibrillation (AF) might cause significant mitral regurgitation (MR), and to see
      whether this MR improves with restoration of sinus rhythm. BACKGROUND: MR can be
      classified by leaflet pathology (organic/primary and functional/secondary) and by
      leaflet motion (normal, excessive, restrictive). The existence of secondary,
      normal leaflet motion MR remains controversial. METHODS: We performed a
      retrospective cohort study. Patients undergoing first AF ablation at our
      institution (n = 828) were screened. Included patients had echocardiograms at the
      time of ablation and at 1-year clinical follow-up. The MR cohort (n = 53) had at
      least moderate MR. A reference cohort (n = 53) was randomly selected from those
      patients (n = 660) with mild or less MR. Baseline echocardiographic and clinical
      characteristics were compared, and the effect of restoration of sinus rhythm was
      assessed by follow-up echocardiograms. RESULTS: MR patients were older than
      controls and more often had persistent AF (62% vs. 23%, p < 0.0001). MR patients
      had larger left atria (volume index: 32 cm(3)/m(2) vs. 26 cm(3)/m(2), p = 0.008)
      and annular size (3.49 cm vs. 3.23 cm, p = 0.001), but similar left ventricular
      size and ejection fraction. Annular size, age and persistent AF were
      independently associated with MR. On follow-up echocardiogram, patients in
      continuous sinus rhythm had greater reductions in left atrial size and annular
      dimension, and lower rates of significant MR (24% vs. 82%, p = 0.005) compared
      with those in whom sinus rhythm was not restored. CONCLUSIONS: AF can result in
      "atrial functional MR" that improves if sinus rhythm is restored.

PMID- 21939834
TI  - Incidence and predictors of implantable cardioverter-defibrillator therapy in
      patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy
      undergoing implantable cardioverter-defibrillator implantation for primary
      prevention.
AB  - OBJECTIVES: The purpose of this study was to define the incidence and predictors
      of implantable cardioverter-defibrillator (ICD) therapy in patients with
      arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) after
      placement of an ICD for primary prevention. BACKGROUND: Patients with a diagnosis
      of ARVD/C often receive an ICD for prevention of sudden cardiac death. METHODS:
      Patients (n = 84) from the Johns Hopkins registry with definite or probable
      ARVD/C who underwent ICD implantation for primary prevention were studied.
      Detailed phenotypic, genotype, and ICD event information was obtained and
      appropriate ICD therapies were adjudicated based on intracardiac electrograms.
      RESULTS: Over a mean follow-up of 4.7 +/- 3.4 years, appropriate ICD therapy was
      seen in 40 patients (48%), of whom 16 (19%) received interventions for
      potentially fatal ventricular fibrillation/flutter episodes. Proband status (p <
      0.001), inducibility at electrophysiologic study (p = 0.005), presence of
      nonsustained ventricular tachycardia (p < 0 .001), and Holter premature
      ventricular complex count >1,000/24 h (p = 0.024) were identified as significant
      predictors of appropriate ICD therapy. The 5-year survival free of appropriate
      ICD therapy for patients with 1, 2, 3, and 4 risk factors was 100%, 83%, 21%, and
      15%, respectively. Inducibility at electrophysiologic study (hazard ratio: 4.5,
      95% confidence interval: 1.4 to 15, p = 0.013) and nonsustained ventricular
      tachycardia (hazard ratio: 10.5, 95% confidence interval: 2.4 to 46.2, p = 0.002)
      remained as significant predictors on multivariable analysis. CONCLUSIONS: Nearly
      one-half of the ARVD/C patients with primary prevention ICD implantation
      experience appropriate ICD interventions. Inducibility at electrophysiologic
      study and nonsustained ventricular tachycardia are independent strong predictors
      of appropriate ICD therapy. An increase in ventricular ectopy burden was
      associated with progressively lower event-free (appropriate ICD interventions)
      survival. Incremental risk of ventricular arrhythmias and ICD therapy was
      observed with the presence of multiple risk factors.

PMID- 21939836
TI  - Left ventricular ejection fraction in addition to N-terminal pro-B-type
      natriuretic peptide for risk stratification in the ambulant elderly: get the
      picture...or not?

PMID- 21939837
TI  - Geriatric congenital heart disease: burden of disease and predictors of
      mortality.
AB  - OBJECTIVES: The study sought to measure the prevalence, disease burden, and
      determinants of mortality in geriatric adults with congenital heart disease
      (ACHD). BACKGROUND: The population of ACHD is increasing and aging. The geriatric
      ACHD population has yet to be characterized. METHODS: Population-based cohort
      study using the Quebec Congenital Heart Disease Database of all patients with
      congenital heart disease coming into contact with the Quebec healthcare system
      between 1983 and 2005. Subjects with specific diagnoses of congenital heart
      disease and age 65 years at time of entry into the cohort were followed for up to
      15 years. The primary outcome was all-cause mortality. RESULTS: The geriatric
      ACHD cohort consisted of 3,239 patients. From 1990 to 2005, the prevalence of
      ACHD in older adults remained constant from 3.8 to 3.7 per 1,000 indexed to the
      general population (prevalence odds ratio: 0.98; 95% confidence interval [CI]:
      0.93 to 1.03). The age-stratified population prevalence of ACHD was similar in
      older and younger adults. The most common types of congenital heart disease
      lesions in older adults were shunt lesions (60%), followed by valvular lesions
      (37%) and severe congenital heart lesions (3%). Type of ACHD and ACHD-related
      complications had a minor impact on mortality, which was predominantly driven by
      acquired comorbid conditions. The most powerful predictors of mortality in the
      Cox proportional hazards model were: dementia (hazard ratio [HR]: 3.24; 95% CI:
      1.53 to 6.85), gastrointestinal bleed (HR: 2.79; 95% CI: 1.66 to 4.69), and
      chronic kidney disease (HR: 2.50; 95% CI: 1.72 to 3.65). CONCLUSIONS: The
      prevalence of geriatric ACHD is substantial, although severe lesions remain
      uncommon. ACHD patients that live long enough acquire general medical
      comorbidities, which are the pre-eminent determinants of their mortality.

PMID- 21939835
TI  - Left ventricular ejection fraction assessment in older adults: an adjunct to
      natriuretic peptide testing to identify risk of new-onset heart failure and
      cardiovascular death?
AB  - OBJECTIVES: The goal of this paper was to determine whether assessment of left
      ventricular ejection fraction (LVEF) enhances prediction of new-onset heart
      failure (HF) and cardiovascular mortality over and above N-terminal pro-B-type
      natriuretic peptide (NT-proBNP) level in older adults. BACKGROUND: Elevated NT
      proBNP levels are common in older adults and are associated with increased risk
      of HF. METHODS: NT-proBNP and LVEF were measured in 4,137 older adults free of
      HF. Repeat measures of NT-proBNP were performed 2 to 3 years later and
      echocardiography was repeated 5 years later (n = 2,375), with a median follow-up
      of 10.7 years. The addition of an abnormal (<55%) LVEF (n = 317 [7.7%]) to
      initially elevated or rising NT-proBNP levels was evaluated to determine risk of
      HF or cardiovascular mortality. Changes in NT-proBNP levels were also assessed
      for estimating the risk of conversion from a normal to abnormal LVEF. RESULTS:
      For participants with a low baseline NT-proBNP level (<190 pg/ml; n = 2,918),
      addition of an abnormal LVEF did not improve the estimation of risk of HF and
      identified a moderate increase in adjusted risk for cardiovascular mortality
      (hazard ratio: 1.69 [95% confidence interval: 1.22 to 2.31]). Among those whose
      NT-proBNP subsequently increased >=25% to >=190 pg/ml, an abnormal LVEF was
      likewise associated with an increased risk of cardiovascular mortality but not
      HF. Participants with an initially high NT-proBNP level (>=190 pg/ml) were at
      greater risk overall for both outcomes, and those with an abnormal LVEF were at
      the highest risk. However, an abnormal LVEF did not improve model classification
      or risk stratification for either endpoint when added to demographic factors and
      change in NT-proBNP. An initially elevated NT-proBNP or rising level was
      associated with an increased risk of developing an abnormal LVEF. CONCLUSIONS:
      Assessment of LVEF in HF-free older adults based on NT-proBNP levels should be
      considered on an individual basis, as such assessments do not routinely improve
      prognostication.

PMID- 21939838
TI  - Asymptomatic displacement of the inflow cannula of a patient 18 months after
      implantation of a DuraHeart left ventricular assist device.

PMID- 21939840
TI  - Epilepsy surgery: the emerging field of neuromodulation.

PMID- 21939839
TI  - Effect of canrenone on left ventricular mechanics in patients with mild systolic
      heart failure and metabolic syndrome: the AREA-in-CHF study.
AB  - BACKGROUND AND AIM: We analyzed the effect of the mineralocorticoid receptor
      antagonist canrenone on LV mechanics in patients with or without metabolic
      syndrome (MetS) and compensated (Class II NYHA) heart failure (HF) with reduced
      ejection fraction (EF<=45%) on optimal therapy (including ACE-i or ARB, and beta
      blockers). METHODS AND RESULTS: From a randomized, double-blind placebo
      controlled trial (AREA-in-CHF), patients with (73 on canrenone [Can] and 77 on
      placebo [Pla]), based on modified ATPIII definition (BMI>=30kg/m(2) instead of
      waist girth) or without MetS (146 by arm). In addition to traditional
      echocardiographic parameters, we also evaluated myocardial mechano-energetic
      efficiency (MME) based on a previously reported method. At baseline, Can and Pla
      did not differ in age, BMI, blood pressure (BP), metabolic profile, BNP, and
      PIIINP. Compared with MetS-Pla, and controlling for age, sex and diabetes, at the
      final control MetS-Can exhibited increased MME, preserved E/A ratio, and
      decreased atrial dimensions (0.04<p<0.0001). At baseline, degree of diastolic
      dysfunction was similar in MetS-Can and MetS-Pla but after 12 months, diastolic
      function improved in MetS-Can, compared to MetS-Pla (p<0.002): moderate-to-severe
      diastolic dysfunction decreased from 26% to 12% with canrenone whereas it was
      unchanged with placebo (both 26%). Can, but not Pla, reduced BNP in both patients
      with or without MetS (p<0.0001). CONCLUSIONS: Treatment with canrenone given on
      the top of optimal therapy in patients with MetS and chronic, stabilized HF with
      reduced EF, protects deterioration of MME, improves diastolic dysfunction and
      maximizes the decrease in BNP.

PMID- 21939842
TI  - Efficacy of vagus nerve stimulation for epilepsy by patient age, epilepsy
      duration, and seizure type.
AB  - Medically refractory epilepsy is a morbid condition, and many patients are poor
      candidates for surgical resection because of multifocal seizure origin or
      eloquence near epileptic foci. Vagus nerve stimulation (VNS) was approved in 1997
      by the US Food and Drug Administration as an adjunctive treatment of intractable
      epilepsy for individuals aged 12 years and more with partial epilepsy.
      Controversy persists regarding the efficacy of VNS for epilepsy and about which
      patient populations respond best to therapy. In this article, the authors
      retrospectively studied a patient outcome registry and report the largest, to
      their knowledge, analysis of VNS outcomes in epilepsy.

PMID- 21939843
TI  - Trigeminal nerve stimulation: seminal animal and human studies for epilepsy and
      depression.
AB  - The unique ability to stimulate bilaterally, extracranially, and non-invasively
      may represent a significant advantage to invasive neuromodulation therapies. In
      humans thus far the technique has been applied noninvasively, and is termed
      external trigeminal nerve stimulation (eTNSTM).

PMID- 21939844
TI  - Thalamic stimulation for epilepsy.
AB  - With the growing applications for deep brain stimulators (DBS) in recent years,
      interest in using DBS as an option for patients with epilepsy has increased.
      Thalamic DBS appears to be a viable minimally invasive treatment for patients
      experiencing medically intractable seizures. Thalamic DBS has been associated
      with significant reduction in seizure frequency and an improvement in overall
      quality of life, especially in patients who have failed maximal antiepileptic
      drugs or other surgical alternatives. However, further work is necessary to
      identify the subgroups of patients experiencing medically intractable seizures
      who may benefit from DBS, and also to indentify optimal stimulation parameters
      and mode of stimulation.

PMID- 21939845
TI  - Hippocampal stimulation in the treatment of epilepsy.
AB  - Neuromodulation is one of the fastest growing fields in neurosurgery, as
      reflected by the growing interest in the use of electrical brain stimulation
      (EBS) to treat drug-resistant epilepsy, pain, and movement disorders. Hippocampal
      stimulation should be regarded as an experimental therapy for epilepsy, and
      patients considered for this intervention should do so in the context of a well
      designed randomized controlled trial. Only well-conducted, blinded, randomized
      trials, followed by long-term systematic observation will yield a clear picture
      of the effect of this promising therapy, and will help guide its future use. This
      article provides a critical review of the best available evidence on hippocampal
      stimulation for epilepsy.

PMID- 21939841
TI  - Electrical stimulation for epilepsy: experimental approaches.
AB  - Direct electrical stimulation of the brain is an increasingly popular means of
      treating refractory epilepsy. Although there has been moderate success in human
      trials, the rate of seizure freedom does not yet compare favorably to resective
      surgery. It therefore remains critical to advance experimental investigations
      aimed toward understanding brain stimulation and its utility. This article
      introduces the concepts necessary for understanding these experimental studies,
      describing recording and stimulation technology, animal models of epilepsy, and
      various subcortical targets of stimulation. Bidirectional and closed-loop device
      technologies are also highlighted, along with the challenges presented by their
      experimental use.

PMID- 21939846
TI  - Responsive neurostimulation for the treatment of epilepsy.
AB  - Neurostimulation in epilepsy has witnessed a century-long evolution that has
      resulted in the use of neurostimulation to both modulate and suppress abnormal
      neuronal firing. The recent development of advanced responsive stimulation via a
      closed-loop device (the RNS System) has provided evidence that surgical epilepsy
      treatment continues to move toward the possibility of reducing or eliminating
      seizures in medically refractory patients.

PMID- 21939847
TI  - Responsive neurostimulation suppresses synchronized cortical rhythms in patients
      with epilepsy.
AB  - Deep brain stimulation (DBS) is an established treatment for Parkinson's disease,
      and is increasingly used for other neuropsychiatric conditions including
      epilepsy. Nevertheless, neural mechanisms for DBS and other forms of
      neurostimulation remain elusive. The authors measured effects of responsive
      neurostimulation on intracranially recorded activity from participants in a
      clinical investigation to assess the safety of an implantable responsive
      neurostimulation system in epilepsy (RNSTM System, NeuroPace, Inc.).
      Neurostimulation acutely suppressed gamma frequency (35-100 Hz) phase-locking.
      This may represent a therapeutic mechanism by which responsive neurostimulation
      can suppress epileptiform activity and disconnect stimulated regions from
      downstream targets in epilepsy and other neuropsychiatric conditions.

PMID- 21939849
TI  - Features and futures: seizure detection in partial epilepsies.
AB  - Many factors underlying basic epileptic conditions determine the characteristics
      of epileptic seizures and the therapeutic outcome. Diagnosis and treatment rely
      on the clinical manifestations as well as electroencephalographic (EEG) epileptic
      activities. This article briefly reviews the fundamentals of the EEG, interictal,
      and ictal electrical activities of both extracranial and intracranial EEG of
      partial epilepsies, based on the information obtained from epilepsy patients who
      have undergone epilepsy surgery. The authors also present the status of their
      current research, focusing on decomposed seizure sources and the rendered spatial
      temporal transitions in focal seizure.

PMID- 21939848
TI  - Seizure prediction and its applications.
AB  - Epilepsy is characterized by intermittent, paroxysmal, hypersynchronous
      electrical activity that may remain localized and/or spread and severely disrupt
      the brain's normal multitask and multiprocessing function. Epileptic seizures are
      the hallmarks of such activity. The ability to issue warnings in real time of
      impending seizures may lead to novel diagnostic tools and treatments for
      epilepsy. Applications may range from a warning to the patient to avert seizure
      associated injuries, to automatic timely administration of an appropriate
      stimulus. Seizure prediction could become an integral part of the treatment of
      epilepsy through neuromodulation, especially in the new generation of closed-loop
      seizure control systems.

PMID- 21939850
TI  - Implanted subdural electrodes: safety issues and complication avoidance.
AB  - Invasive electroencephalography via subdural implanted electrodes is essential
      for the identification and localization of the epileptogenic focus in a large
      percentage of cases of medically refractory epilepsy. The implantation of
      subdural electrodes constitutes a widely used method for the preoperative
      investigation of these patients. However, their implantation has been associated
      with the occurrence of some rare but potentially serious complications. This
      article systematically reviews the literature regarding safety issues, potential
      complications, and complication avoidance strategies associated with the
      implantation of subdural electrodes. Knowledge of all the reported complications
      may help in their early detection and their prompt management.

PMID- 21939851
TI  - Focal cooling devices for the surgical treatment of epilepsy.
AB  - Focal cooling may provide a safe, nondestructive alternative to resective and
      disconnective strategies that have been proposed or used to control refractory
      epilepsy. Observations of the effects of direct application of iced saline on the
      cortical surface during cortical mapping surgery and induced seizures have led to
      interest in developing implantable cooling therapy devices for refractory
      localizable epilepsies. In this article, the authors provide an overview of the
      historical background, physiology, and animal and human data leading to the
      development of implantable cooling devices for the treatment of medically
      refractory epilepsy.

PMID- 21939852
TI  - Overview: Where does radiation therapy fit in the spectrum of liver cancer local
      regional therapies?
AB  - Experience with radiation therapy for the treatment of hepatocellular carcinoma
      (HCC) and liver metastases has increased rapidly in the past decade. This is
      principally because of advances in imaging and radiation techniques that can
      conform high doses to focal cancers and to a better understanding of how to avoid
      radiation-induced liver toxicity. Guidelines on how to use radiation therapy
      safely are becoming more clearly established, and reports of tumor control at 2
      to 5 years show the potential for cure after radiation therapy for early-stage
      HCC and liver metastases. For both HCC and liver metastases, the best outcomes
      after radiation therapy are found in patients with fewer than 3 lesions that are
      <6 cm in size, with intact liver function and no extrahepatic metastases. There
      is a strong rationale for using radiation therapy in patients unsuitable for or
      with expected poor outcomes after standard local-regional therapies. These
      patients tend to have advanced tumors (large, multifocal, or invading vessels)
      and/or impaired liver function, reducing the chance of cure and increasing the
      chance of toxicity. In these patients, the benefits of radiation therapy over
      systemic therapy or best supportive therapy should be established in randomized
      trials.

PMID- 21939853
TI  - Imaging and image-guided radiation therapy in liver cancer.
AB  - Imaging for radiation therapy treatment planning and delivery is a critical
      component of the radiation planning process for liver cancer. Because of the lack
      of inherent contrast between liver tumors and the surrounding liver, intravenous
      contrast is required for accurate target delineation on the planning computed
      tomography scan. The appropriate phase of contrast is tumor specific, with
      arterial phase imaging usually used to define hepatocellular carcinoma and venous
      phase imaging for vascular thrombosis related to hepatocellular carcinoma and
      most types of liver metastases. Breathing motion and changes in the liver
      position day to day may be substantial and need to be considered at the time of
      radiation planning and treatment. Many types of integrated imaging-radiation
      treatment systems and image-guidance strategies are available to produce
      volumetric and/or planar imaging at the time of treatment delivery to reduce the
      negative impact of geometric changes that may occur. Image-guided radiation
      therapy facilitates reduced PTV margins and dose escalation and improves the
      precision of radiation therapy, so the prescribed doses are more likely to
      represent those actually delivered.

PMID- 21939854
TI  - Hepatic radiation toxicity: avoidance and amelioration.
AB  - The refinement of radiation therapy and radioembolization techniques has led to a
      resurgent interest in radiation-induced liver disease (RILD). The awareness of
      technical and clinical parameters that influence the chance of RILD is important
      to guide patient selection and toxicity minimization strategies. "Classic" RILD
      is characterized by anicteric ascites and hepatomegaly and is unlikely to occur
      after a mean liver dose of approximately 30 Gy in conventional fractionation. By
      maintaining a low mean liver dose and sparing a "critical volume" of liver from
      radiation, stereotactic delivery techniques allow for the safe administration of
      higher tumor doses. Caution must be exercised for patients with hepatocellular
      carcinoma or pre-existing liver disease (eg, Child-Pugh score of B or C) because
      they are more susceptible to RILD that can manifest in a nonclassic pattern.
      Although no pharmacologic interventions have yet been proven to mitigate RILD,
      preclinical research shows the potential for therapies targeting transforming
      growth factor-beta and for the transplantation of stem cells, hepatocytes, and
      liver progenitor cells as strategies that may restore liver function. Also, in
      the clinical setting of veno-occlusive liver disease after high-dose
      chemotherapy, agents with fibrinolytic and antithrombotic properties can reverse
      liver failure, suggesting a possible role in the setting of RILD.

PMID- 21939855
TI  - Radiation therapy for liver metastases.
AB  - Liver metastases are a common source of cancer morbidity and mortality and are
      often the only site of metastases. In the last 2 decades, major technological
      advancements in radiation treatment planning and delivery have resulted in
      resurgence in the use of radiation therapy (RT) as a treatment for liver tumors.
      With the advent of 3-dimensional conformal radiation treatment (CRT), partial
      liver irradiation became possible. Stereotactic body radiation therapy (SBRT) is
      a further enhancement, defined as highly focused, stereotactically localized and
      administered, high-dose RT delivered in a hypofractionated course. There is now
      more than a decade of experience with CRT and SBRT for the treatment of liver
      metastases. In selected patients, very high local control rates have been
      observed, with minimal toxicity. Patients most likely to benefit from RT are
      those with liver confined disease, focal distribution of metastases, and
      metastases more than 1.5 cm from luminal gastrointestinal organs. There is
      growing evidence that strategies using aggressive or ablative local therapies as
      an adjunct to systemic therapy might achieve improvements in overall outcome as
      long as they are administered safely.

PMID- 21939856
TI  - Radiation therapy for hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide, and
      its incidence is on the rise. The primary therapy is resection or liver
      transplant, but only a minority of patients present with resectable disease.
      Historically, radiotherapy has not played a significant role in the treatment of
      liver malignancies because of the low tolerance of the whole liver to radiation.
      With improvements in 3-dimensional conformal radiotherapy and intensity-modulated
      radiotherapy, higher doses of radiation can be delivered to target lesions with
      low doses to the noninvolved liver; thus, experience in the use of radiation for
      the treatment of focal HCC has increased. At the same time, our understanding of
      the relationships between radiation dose and volume and the risk of classic
      radiation-induced liver disease and other toxicities more likely to occur in HCC
      patients has improved considerably. These developments have led to a body of
      evidence that now supports the careful use of radiotherapy for unresectable HCC.
      The rationale for studying radiotherapy in a randomized trial is strong.

PMID- 21939857
TI  - Charged-particle therapy for hepatocellular carcinoma.
AB  - Historically, the use of external-beam radiotherapy for hepatocellular carcinoma
      (HCC) has been limited by toxicity to the uninvolved liver and surrounding
      structures. Advances in photon radiotherapy have improved dose conformality to
      the tumor and facilitated dose escalation, a key contributor to improved HCC
      radiation treatment outcomes. However, despite these advances in photon
      radiotherapy, significant volumes of liver still receive low doses of radiation
      that can preclude dose escalation, particularly in patients with limited
      functional liver reserves. By capitalizing on the lack of exit dose along the
      beam path beyond the tumor and higher biological effectiveness, charged-particle
      therapy offers the promise of maximizing tumor control via dose escalation
      without excessive liver toxicity. In this review, we discuss the distinctive
      biophysical attributes of both proton and carbon ion radiotherapy, particularly
      as they pertain to treatment of HCC. We also review the available literature
      regarding clinical outcomes and the toxicity of using charged particles for the
      treatment of HCC.

PMID- 21939858
TI  - Computed tomography-guided brachytherapy for liver cancer.
AB  - Limitations of thermal liver cancer ablation have led to the development of
      percutaneous, catheter-based brachytherapy for the treatment of liver
      malignancies. Computed tomography (CT)-guided brachytherapy has been used to
      treat primary and metastatic liver cancers, including very large tumors >10 cm.
      Cooling effects by adjacent blood vessels are not a concern in brachytherapy, and
      the method may be used safely in tumors unsuitable for thermal ablation that are
      close to the liver hilum due to the relatively high radiation tolerance of bile
      duct. CT scanning is used for dosimetry planning after catheter implantation and
      also to guide the catheter placement itself. Major complications, including
      postinterventional bleeding, are rare despite frequent application of this
      technique in a salvage situation. Patients with liver cirrhosis have an increased
      risk for complications. Prospective trials of CT-guided brachytherapy have been
      performed with promising survival rates for liver metastases and hepatocellular
      carcinoma, respectively. In this article, the radiobiological and technical
      properties of CT-guided brachytherapy, appropriate patients for treatment, and
      prospective trials that have been published to date are reviewed.

PMID- 21939860
TI  - Radiosensitizers in hepatocellular carcinoma.
AB  - Most hepatocellular carcinoma (HCC) patients present with locally advanced
      disease with a risk of development of intrahepatic or extrahepatic metastases.
      Conformal radiotherapy (RT) can be delivered to focal HCCs with sustained local
      control in selected HCC patients. However, it is frequently not possible to
      deliver tumoricidal doses to locally advanced HCC due to the risk of radiation
      induced liver toxicity or the risk of toxicity to adjacent luminal
      gastrointestinal organs. Combining RT with radiosensitizers is an attractive
      strategy to increase the therapeutic ratio for these patients. Clinical
      experience in combining RT and radiosensitizers in HCC is limited. Hepatic
      arterial chemoembolization (or transcatheter arterial chemoembolization, TACE)
      has been used in combination with RT for the treatment of HCC, as have
      halogenated pyrimidines. More recently, there is a growing experience of RT
      delivered with molecular targeted agents in HCC. In this review, the rationale
      for potential radiation sensitization and the clinical experience in HCC for
      different classes of radiation sensitizers are discussed.

PMID- 21939859
TI  - Radioembolization for primary and metastatic liver cancer.
AB  - The incidence of hepatocellular carcinoma is increasing. Most patients present
      beyond potentially curative options and are usually affected by underlying
      cirrhosis. In this scenario, transarterial therapies, such as radioembolization,
      are rapidly gaining acceptance as a potential therapy for hepatocellular
      carcinoma and liver metastases. Radioembolization is a catheter-based liver
      directed therapy that involves the injection of micron-sized embolic particles
      loaded with a radioisotope by use of percutaneous transarterial techniques.
      Cancer cells are preferentially supplied by arterial blood and normal hepatocytes
      by portal venous blood; therefore, radioembolization specifically targets tumor
      cells with a high dose of lethal radiation and spares healthy hepatocytes. The
      antitumor effect mostly comes from radiation rather than embolization. The most
      commonly used radioisotope is yttrium-90. The commercially available devices are
      TheraSphere (glass based; MDS Nordion, Ottawa, Canada) and SIR-Sphere (resin
      based; Sirtex, Lane Cove, Australia). The procedure is performed on an outpatient
      basis. The incidence of complications is comparatively less than other
      locoregional therapies and may include nausea, fatigue, abdominal pain, hepatic
      dysfunction, biliary injury, fibrosis, radiation pneumonitis, gastrointestinal
      ulcers, and vascular injury. However, these complications can be avoided by
      meticulous pretreatment assessment, careful patient selection, and adequate
      dosimetry. This article focuses on both the technical and clinical aspects of
      radioembolization with emphasis on patient selection, uses and complications.

PMID- 21939861
TI  - Forging partnerships with parents while delivering adolescent confidential health
      services: a clinical paradox.

PMID- 21939863
TI  - Synthetic cannabinoid use: a case series of adolescents.
AB  - PURPOSE: Synthetic cannabinoid products have been increasingly used by
      adolescents for the past few years, but little literature exists describing their
      psychoactive and physical effects. This study describes the psychoactive and
      physical effects of synthetic cannabinoids as reported by adolescent users.
      METHODS: This study reviewed the records of 11 individuals aged 15-19 years who
      were evaluated at the South Miami Hospital Addiction Treatment Center in Miami
      Dade County, Florida. The average age of the subjects was 17.3 years (standard
      deviation = 1.35; range (R) = 15, 19); 10 of 11 (91%) were male and 10 of 11 were
      Hispanic. The charts of youth who admitted use of synthetic cannabinoids were
      reviewed. Demographic information, characteristics of the substance, and
      descriptions of the psychoactive and physical effects were abstracted from the
      standardized, semi-structured clinician interviews. RESULTS: All the subjects
      reported a feeling of euphoria and memory changes. Nine (82%) reported negative
      mood changes. Marijuana and alcohol use was also reported by 10 (91%) subjects.
      The number of other drugs used was significantly correlated with the frequency of
      synthetic cannabinoid use (r = .896, p < .05). CONCLUSIONS: Adolescent synthetic
      cannabinoid product users report significant psychoactive effects.

PMID- 21939862
TI  - Who decides? Decision making and fertility preservation in teens with cancer: a
      review of the literature.
AB  - PURPOSE: The knowledge that cancer treatment may impair fertility in pediatric
      populations is an emerging aspect of quality of life in this population. However,
      decision making and use of fertility preservation (FP) among adolescent cancer
      patients and their families has not been well studied. This review summarizes the
      available published data on aspects of decision making and FP in adolescent
      cancer patients. METHODS: An electronic search was performed to identify peer
      reviewed studies published between 1999 and 2009 using key Medical Subject
      Heading terms and inclusion criteria. Inclusion criteria limited eligible studies
      to those that focused on adolescent decision making in cancer treatment or FP,
      fertility concerns in pediatric oncology, capacity for decision making, and
      health decision making in pediatrics. Studies that did not meet at least one of
      these criteria were excluded. RESULTS: A total of 29 articles were reviewed and
      summarized. Three categories of results were seen: a focus on adolescent decision
      making in oncology, decision making in chronic illness, and decision making in
      cancer-related infertility and preservation. CONCLUSION: Most of the studies
      showed that adolescents have a strong desire to participate in decisions related
      to their cancer treatment and many have concerns regarding their future
      fertility, although barriers often prevented these discussions. More research is
      needed to explore the role of teenagers and parents in decisions about fertility
      in relation to cancer treatment.

PMID- 21939865
TI  - Transdermal contraception as a model for adolescent use of new methods.
AB  - PURPOSE: To examine the factors related to adolescents' decisions to use the
      transdermal contraceptive patch (patch) so as to develop a model for
      understanding how adolescents decide to use new contraceptive methods. METHODS:
      We conducted in-depth semi-structured interviews with 18 young women aged 15-21
      years who had experience using the patch. Data were analyzed using a two-stage
      method informed by grounded theory. RESULTS: We constructed a two-level model,
      encompassing individual, social, and environmental factors, to explain
      adolescents' decisions to use a new method of hormonal contraception. Social and
      environmental influences on the decision-making process included media, social
      network experiences and opinions, healthcare providers, and partner
      relationships. These in turn affected the following individual factors in the
      decision to use the patch: individual characteristics, method knowledge and
      beliefs, method support, and past contraceptive experience. The newness of the
      patch permeated all levels of the decision-making process. CONCLUSIONS: This
      model provides a framework for understanding the use of new contraceptive methods
      and can inform clinical strategies for contraceptive counseling with adolescents.

PMID- 21939864
TI  - Does competence mediate the associations between puberty and internalizing or
      externalizing problems in adolescent girls?
AB  - PURPOSE: To examine separate mediational models linking (a) menarcheal status or
      (b) pubertal timing to internalizing and externalizing problems through
      competence. METHOD: This study involved cross-sectional analyses of 262
      adolescent girls (age: 11-17 years; mean = 14.93, standard deviation = 2.17)
      enrolled in a longitudinal study examining the association of psychological
      functioning and smoking with reproductive and bone health. Measures of menarcheal
      status (pre/post), pubertal timing (early, on-time, or late), internalizing and
      externalizing behavior, and perceived competence (parent and adolescent report)
      were obtained. Structural equation modeling was used for analyses. RESULTS:
      Perceived competence was found to fully mediate the association between
      menarcheal status and parent report of internalizing and externalizing problems.
      For adolescent report, there was a full mediation effect for internalizing
      problems but a partial mediation effect for externalizing problems. Being
      menarcheal was related to lower competence, which was in turn related to higher
      internalizing and externalizing problems. Models including pubertal timing were
      not significant. CONCLUSIONS: Perceived competence is important in understanding
      the associations between menarcheal status and internalizing and externalizing
      problems. Interventions targeting competence, particularly in postmenarcheal
      girls, may reduce or prevent problem behaviors.

PMID- 21939866
TI  - A multivariate analysis of federally mandated school wellness policies on
      adolescent obesity.
AB  - PURPOSE: To evaluate the effects of school wellness policies mandated by the 2004
      Child Nutrition and WIC Reauthorization Act on the prevalence of overweight and
      obesity among adolescents. METHODS: Multivariate logistic regressions, adjusted
      for clustering within school districts, were used to estimate the effects of
      district-level wellness policies on the odds of overweight and obesity among
      adolescents. The analyses were performed on a population-based sample obtained
      from the Utah Population Database, a compilation of vital characteristic,
      administrative, and genealogical records on all residents in Utah. Models
      controlled for individual, maternal, and familial characteristics, as well as
      characteristics of school district of residence. Self-reported body mass index
      was taken from drivers license data. RESULTS: Each additional component included
      in a district's wellness policy was associated with as much as: 3.2% lower odds
      in the prevalence of adolescent overweight (OR = .968; 95% CI = .941-.997), 2.5%
      lower odds of obesity (OR = .975; CI = .952-.997), and 3.4% lower odds of severe
      obesity (OR = .966; CI = .938-.995). Wellness policy components related to diet
      were significantly associated with lower body mass indexes across all three
      thresholds, whereas those related to physical activity had significant
      associations for lower odds of severe obesity only. CONCLUSION: Results suggest
      that school wellness policies can significantly reduce the risk of adolescent
      obesity. Further research should address specific policy components that are most
      effective in various populations, as well as the level of commitment that is
      required at both the school- and district-levels for sustained effect.

PMID- 21939867
TI  - Participant- and study-related characteristics predicting treatment completion
      and study retention in an adolescent smoking cessation trial.
AB  - PURPOSE: To determine which factors predict smoking cessation treatment
      completion and retention among adolescents. METHODS: In a multisite, randomized,
      controlled trial, the efficacy of motivational interviewing was compared with
      structured brief advice for smoking cessation and reduction in adolescents (n =
      355) aged 14-18 years (55% female, 45% black, 12% Hispanic). Treatment spanned 12
      weeks, with follow-up assessments at 24 weeks. Treatment completion was defined
      as completion of all five counseling sessions. Study retention was defined as
      completing the 24-week assessment. Participant and study variables served as
      predictors of treatment completion and retention. RESULTS: In all, 79% of
      participants completed all five counseling sessions and the same percent
      completed the 24-week assessment. Black race, precontemplation stage to cut back,
      and shorter length of time between the baseline assessment and the first
      counseling session were significantly associated with treatment completion. For
      every 7.5-day delay in starting treatment after the baseline visit, there was a
      50% decrease in the odds of completing all five treatment sessions. Retention at
      24 weeks was predicted by black race, younger age, greater maternal education,
      expectations of graduating college, and structured brief advice intervention.
      CONCLUSIONS: High rates of treatment completion and study retention can be
      achieved in a multisession, behavioral intervention for adolescent smoking
      cessation. Findings suggest that treatment should begin soon after the intake
      session to maximize treatment completion. Enhanced efforts to retain older
      adolescents and youth with lower academic goals and lower family income will be
      important in future studies.

PMID- 21939868
TI  - Building conditions, 5-HTTLPR genotype, and depressive symptoms in adolescent
      males and females.
AB  - PURPOSE: Emerging work suggests that both environmental and genetic factors
      contribute to risk of depression in adolescents, and that these factors may
      differ between genders. We assessed whether features of the social environment
      (SE), measured at varying levels, and genetic factors jointly contribute to the
      risk of depression in adolescent males and females. METHODS: Using data from a
      national survey of U.S. adolescents, we applied cross-sectional, multilevel mixed
      models to assess the contribution of: (i) 5-HTTLPR genotype and respondent-level
      building conditions to depressive symptom score (DSS); and (ii) 5-HTTLPR genotype
      and neighborhood-level building conditions to DSS. Models testing potential gene
      SE interactions were also conducted. All models were stratified by gender and
      adjusted for age, race/ethnicity, family structure, parental education, and
      social support. RESULTS: Among females, adjusted analyses indicated that sl
      genotype carriers enjoyed a marginally significant (p = .07) protective effect
      against higher DSS in models assessing respondent-level building conditions. In
      contrast, among males, adjusted analyses predicted significantly higher DSS for
      residents of neighborhoods with relatively poor building conditions (p < .01). No
      significant gene-SE interactions were detected for either gender. CONCLUSIONS:
      These results suggest that adverse, macro-level SE factors increase risk of
      depression to a greater extent in adolescent males than in females. Intervention
      strategies designed to improve mental health in adolescent populations should
      consider a growing body of work suggesting that the contextual factors conferring
      increased risk of depression differ among males and females.

PMID- 21939869
TI  - Adolescents' cortisol reactivity and subjective distress in response to family
      conflict: the moderating role of internalizing symptoms.
AB  - PURPOSE: Internalizing symptoms have been associated with both higher and blunted
      cortisol responses in adolescents. Little attention has been paid to subjective
      experiences of distress in conjunction with internalizing symptoms in
      hypothalamic-pituitary-adrenal axis responses to laboratory stressors. The
      present study examines whether adolescents' internalizing symptoms moderate the
      association between cortisol responses and distress in response to a common
      stressor in adolescence: family conflict. Differences are also examined between
      adolescents with current, past only, and no history of internalizing symptoms.
      METHODS: Adolescents (N = 70) discussed areas of conflict with their parents and
      subsequently reported on distress experienced during the discussion. Baseline and
      five poststressor saliva samples were collected. Adolescents' internalizing
      symptoms were assessed concurrently with the discussion and at three previous
      time-points. RESULTS: Internalizing symptoms moderated the association between
      distress reported by the adolescents and cortisol reactivity in response to
      family conflict. Adolescents with current and past internalizing symptoms had a
      blunted cortisol response, whereas adolescents with no history of internalizing
      symptoms showed greater cortisol reactivity when reporting greater distress.
      CONCLUSIONS: This study expands the understanding of how current and remitted
      internalizing symptoms are related to adolescents' responses to everyday family
      conflicts. Adolescents with current and past internalizing symptoms demonstrated
      a lack of correspondence between psychological and physiological stress, whereas
      adolescents with no history of internalizing symptoms showed the anticipated
      correspondence. This study has important implications for understanding the link
      between internalizing symptoms and adolescents' hypothalamic-pituitary-adrenal
      functioning in response to common social stressors.

PMID- 21939870
TI  - Linkages between gender equity and intimate partner violence among urban
      Brazilian youth.
AB  - PURPOSE: Gender inequity is a risk factor for intimate partner violence (IPV),
      although there is little research on this relationship that focuses on youth or
      males. Using survey data collected from 240 male and 198 female youth aged 15-24
      in Rio de Janeiro, Brazil, we explore the association between individual-level
      support for gender equity and IPV experiences in the past 6 months and describe
      responses to and motivations for IPV. METHODS: Factor analysis was used to
      construct gender equity scales for males and females. Logistic and multinomial
      logistic regression models were used to examine the relationship between gender
      equity and IPV. RESULTS: About half of female youth reported some form of recent
      IPV, including any victimization (32%), any perpetration (40%), and both
      victimization and perpetration (22%). A total of 18% of male youth reported
      recently perpetrating IPV. In logistic regression models, support for gender
      equity had a protective effect against any female IPV victimization and any male
      IPV perpetration and was not associated with female IPV perpetration. Female
      victims reported leaving the abusive partner, but later returning to him as the
      most frequent response to IPV. Male perpetrators said the most common response of
      their victims was to retaliate with violence. Jealousy was the most frequently
      reported motivation of females perpetrating IPV. CONCLUSION: Gender equity is an
      important predictor of IPV among youth. Examining the gendered context of IPV
      will be useful in the development of targeted interventions to promote gender
      equity and healthy relationships and to help reduce IPV among youth.

PMID- 21939871
TI  - Association of socioeconomic status, problem behaviors, and disordered eating in
      Mexican adolescents: results of the Mexican National Health and Nutrition Survey
      2006.
AB  - PURPOSE: To explore the association of socioeconomic status (SES) with disordered
      eating behaviors (DEB) in Mexican adolescents, and the coexistence of DEB and
      other problem behaviors. METHODS: Information about adolescents (10-19 years) was
      retrieved from the Mexican National Health and Nutrition Survey 2006 database.
      Associations were evaluated through ordinal regression. RESULTS: Higher SES was
      associated with DEB (odds ratio [OR]: 2.05, 95% confidence interval [CI]: 1.52
      2.75). Use of tobacco (OR: 2.10, 95% CI: 1.58-2.81), alcohol (OR: 2.03, 95% CI:
      1.51-2.56), and suicide intent (OR: 5.13, 95% CI: 3.46-7.60) were associated with
      DEB. CONCLUSION: DEB were more frequent among adolescents from higher SES
      households. The lack of association between SES and DEB reported by other studies
      might be because of the lack of variability in samples. The association of DEB
      and other problem behaviors highlights the importance of an integral approach to
      teenagers' mental health.

PMID- 21939872
TI  - The influence of school demographic factors and perceived student discrimination
      on delinquency trajectory in adolescence.
AB  - PURPOSE: The purpose of this study was to examine the effects of school
      demographic factors and youth's perception of discrimination on delinquency in
      adolescence and into young adulthood for African American, Asian, Hispanic, and
      white racial/ethnic groups. METHODS: Using data from the National Longitudinal
      Study of Adolescent Health (Add Health), models testing the effect of school
      related variables on delinquency trajectories were evaluated for the four
      racial/ethnic groups using Mplus 5.21 statistical software. RESULTS: Results
      revealed that greater student ethnic diversity and perceived discrimination, but
      not teacher ethnic diversity, resulted in higher initial delinquency estimates at
      13 years of age for all groups. However, except for African Americans, having a
      greater proportion of female teachers in the school decreased initial delinquency
      estimates. For African Americans and whites, a larger school size also increased
      the initial estimates. Additionally, lower social-economic status increased the
      initial estimates for whites, and being born in the United States increased the
      initial estimates for Asians and Hispanics. Finally, regardless of the initial
      delinquency estimate at age 13 and the effect of the school variables, all groups
      eventually converged to extremely low delinquency in young adulthood, at the age
      of 21 years. CONCLUSION: Educators and public policy makers seeking to prevent
      and reduce delinquency can modify individual risks by modifying characteristics
      of the school environment. Policies that promote respect for diversity and
      intolerance toward discrimination, as well as training to help teachers recognize
      the precursors and signs of aggression and/or violence, may also facilitate a
      positive school environment, resulting in lower delinquency.

PMID- 21939873
TI  - The decision to access patient information from a social media site: what would
      you do?
AB  - PURPOSE: The current study examined the prevalence with which healthcare
      providers use a social media site (SMS) account (e.g., Facebook), the extent to
      which they use SMSs in clinical practice, and their decision-making process after
      accessing patient information from an SMS. METHODS: Pediatric faculty and
      trainees from a medical school campus were provided a SMS history form and seven
      fictional SMS adolescent profile vignettes that depicted concerning information.
      Participants were instructed to rate their personal use and beliefs about SMSs
      and to report how they would respond if they obtained concerning information
      about an adolescent patient from their public SMS profile. RESULTS: Healthcare
      providers generally believed it not to be an invasion of privacy to conduct an
      Internet/SMS search of someone they know. A small percentage of trainees reported
      a personal history of conducting an Internet search (18%) or an SMS search (14%)
      for a patient. However, no faculty endorsed a history of conducting searches for
      patients. Faculty and trainees also differed in how they would respond to
      concerning SMS adolescent profile information. CONCLUSIONS: The findings that
      trainees are conducting Internet/SMS searches of patients and that faculty and
      trainees differ in how they would respond to concerning profile information
      suggest the need for specific guidelines regarding the role of SMSs in clinical
      practice. Practice, policy, and training implications are discussed.

PMID- 21939874
TI  - Homophily and contagion as explanations for weight similarities among adolescent
      friends.
AB  - PURPOSE: To determine whether weight-based similarities among adolescent friends
      result from social influence processes, after controlling for the role of weight
      on friendship selection and other confounding influences. METHODS: Four waves of
      data were collected from a grade 8 cohort of adolescents (N = 156, mean age =
      13.6 years) over their initial 2 years of high school. At each wave, participants
      reported on their friendship relations with grade-mates and had their height and
      weight measured by researchers to calculate their body mass index (BMI). Newly
      developed stochastic actor-oriented models for social networks were used to
      simultaneously assess the role of weight on adolescents' friendship choices, and
      the effect of friends' BMIs on changes in adolescent BMI. RESULTS: Adolescents'
      BMIs were not significantly predicted by the BMI of their friends over the 16
      months of this study. Similarities in the weights of friends were found to be
      driven predominantly by friendship selection, whereby adolescents, particularly
      those who were not overweight, preferred to initiate friendships with peers whose
      weight status (overweight/nonoverweight) was the same as their own. CONCLUSIONS:
      Weight-based similarities among friends were largely explained by the
      marginalization of overweight adolescents by their peers, rather than by the
      "contagion" of excess weight among friends. These findings highlight the
      importance of adequately modeling friendship selection processes when estimating
      social influence effects on adiposity.

PMID- 21939875
TI  - Confidentiality with adolescents in the medical setting: what do parents think?
AB  - PURPOSE: When confidential health care is provided to adolescents they are more
      likely to seek care, disclose sensitive information, and return for future
      visits. Guidelines for health professionals recommend seeing young people alone
      to facilitate confidential care. We sought to document parental views regarding
      confidentiality with adolescents, aiming to identify topics that parents believe
      they should be informed about despite an assurance of confidentiality between
      their child and the doctor. We also aimed to document harms and benefits that
      parents associate with adolescents seeing doctors alone. METHODS: A sample of 86
      parents attending an adolescent medicine clinic with their son/daughter was
      surveyed using a brief, anonymous questionnaire. RESULTS: Parents identified
      several benefits associated with confidential care, yet also believed they should
      be informed about a wide range of topics, even if their children did not want
      them to know. Parents' primary concern about confidentiality was a fear of not
      being informed about important information. CONCLUSIONS: Parental views
      concerning confidentiality are complex and conflicting and differ from current
      guidance provided to health professionals. Ensuring that parents accurately
      understand the limits to confidentiality and support the notion of confidential
      care for their children is a challenging yet vital task for health professionals.

PMID- 21939876
TI  - Relationship of training to self-reported competency and care of adolescents in
      an African health care setting.
AB  - PURPOSE: Adolescent medicine is not a recognized specialty in most African
      countries and African healthcare providers receive little adolescent-specific
      training. We explored the association between training, self-reported competence,
      and clinical practice related to adolescent health in an African setting.
      METHODS: A total of 119 healthcare providers of various disciplines who work with
      adolescent patients in Francistown, Botswana were surveyed regarding their
      adolescent-specific training, self-reported competence, and counseling practices.
      Self-reported competence and practices related to counseling adolescents about
      sexual activity, alcohol and/or drug use, human immunodeficiency virus (HIV)
      specific issues, and mental health were explored. RESULTS: In all, 50.4% of
      respondents had received HIV training with an adolescent-specific component.
      Fewer had received adolescent-specific training outside the context of HIV
      prevention and management. Respondents were significantly more likely to report
      higher competence for all items except for counseling adolescents about
      depression and anxiety if they had received any adolescent-specific training.
      Respondents who reported higher competence were significantly more likely to
      report more frequent counseling of their adolescent clients. CONCLUSIONS: Our
      study suggests that adolescent-focused training is important for ensuring that
      adolescents receive counseling when presenting for routine healthcare in our
      setting. The mental health needs of adolescents do not seem to be adequately
      addressed by current training.

PMID- 21939877
TI  - Pubertal maturation of contemporary Greek boys: no evidence of a secular trend.
AB  - PURPOSE: To examine pubertal status of contemporary Greek boys and compare the
      data with those of a previous study we performed in the year 1996. METHODS: We
      performed a cross-sectional study of 932 healthy boys, aged from 8.05 to 16.05
      years. Development of the genitalia (G) and pubic hair was assessed by the method
      of Tanner and testicular volume (TV) was determined with a Prader orchidometer.
      Genitalia stage 2 (G2) was assessed by probit analysis. RESULTS: Median (95%
      confidence interval [CI]) age at G2, defined as TV 4 mL, was 11.3 (10.9-11.6)
      years, almost the same age as in our study performed in 1996, which was 11.4
      (10.7-11.7) years (p = .21). When G2 was defined as change in scrotum texture and
      TV2 mL, median (95% CI) age at onset of puberty was 10.9 (10.5-11.3) years, again
      similar to the study performed in 1996 which was 11.0 (10.7-11.4) (p = .32).
      Median (95% CI) age of pubic hair development was 11.2 (10.8-11.6) years versus
      11.5 (11.1-12.0) years in 1996, p = .015. CONCLUSIONS: Our data provide no
      evidence of a secular trend for gonadarche in Greek boys, although such a trend
      was evident for pubarche.

PMID- 21939879
TI  - Autism spectrum disorders and menstruation.
AB  - We assessed the experience of 10-25-year old women with autism spectrum disorders
      with menstruation through their caregivers by investigating hygiene concerns,
      dysmenorrhea, premenstrual syndrome, and treatments. Frequent and severe symptoms
      of dysmenorrhea and premenstrual syndrome were common but had moderate morbidity
      rates. Hormonal contraception and other treatments were underused.

PMID- 21939878
TI  - Alcohol use as a potential mediator of forced sexual intercourse and suicidality
      among African American, Caucasian, and Hispanic high school girls.
AB  - PURPOSE: Sexual assault on adolescent females is a major public health concern.
      The purposes of this study were to examine: (1) whether alcohol use mediates the
      relationship between forced sexual intercourse and suicidality in high-school
      girls, and (2) whether this mediation differs by ethnicity. METHODS: Using cross
      sectional data from the 2009 Youth Risk Behavior Survey (n = 6,294), we used
      logistic regression and simple mediation using the Sobel test for indirect effect
      for our analyses. RESULTS: Overall rates for forced sexual intercourse, alcohol
      use, and suicidality were 10.9%, 56.6%, and 18%, respectively. Current alcohol
      use significantly mediated the relationship between forced sexual intercourse and
      suicidality in African American, Caucasian, and Hispanic high-school girls.
      Overall, 13% of variance in participants' suicidality can be accounted for by the
      indirect effect of forced sexual intercourse on suicidality through alcohol use.
      The amount of variance accounted for by alcohol use varied significantly by
      ethnicity, with the largest amount of variance (21%) accounted for suicidality in
      Hispanic girls. CONCLUSION: In addition to its acute affects, alcohol use may
      serve as a general risk factor for suicidality in girls who have experienced
      forced sexual intercourse. Intervention programs targeting female adolescent
      sexual assault victims should include an alcohol use component.

PMID- 21939881
TI  - The unsung heroes.

PMID- 21939882
TI  - Use of ephedrine for the short-term treatment of postoperative nausea and
      vomiting: a case report.
AB  - Ephedrine, a well-known sympathomimetic agent, is used in the perioperative
      setting to treat acute hypotension, especially hypotension related to anesthetic
      events. Ephedrine's unlabeled use as an antiemetic agent is less well known
      despite its efficacy and safety profile for short-term and/or prophylactic
      treatment. The following case report describes the benefits of using ephedrine to
      mitigate postoperative nausea and vomiting and associated dizziness while waiting
      for longer lasting therapy to take effect and/or use as a secondary agent.

PMID- 21939880
TI  - Association of web-based weight loss information use with weight reduction
      behaviors in adolescent women.
AB  - PURPOSE: To examine the association between seeking weight loss information from
      the Internet and weight loss behaviors. METHODS: A self-administered survey was
      conducted on 3,181 women, aged 16-24 years, between August 2008 and August 2010.
      Questions were asked on use of the Internet to obtain weight loss information and
      various weight loss practices. Multivariate logistic regression analyses were
      performed to examine the association between seeking weight loss information
      online and practicing these weight loss behaviors. RESULTS: In all, 39% used the
      Internet to seek weight loss information. Women who obtained weight loss
      information from the Internet were more likely to exercise (odds ratio [OR]:
      1.31, 95% confidence interval [CI]: 1.07-1.60), use diet pills (OR: 4.14, 95% CI:
      2.93-5.84), laxatives (OR: 2.02, 95% CI: 1.15-3.54), diuretics (OR: 7.89, 95% CI:
      2.88-21.61), vomit after eating (OR: 2.56, 95% CI: 1.24-5.30), skip meals (OR:
      2.77, 95% CI: 2.26-3.39), smoke more cigarettes (OR: 1.56, 95% CI: 1.14-2.14),
      and stop eating carbohydrates (OR: 3.09, 95% CI: 1.81-5.26) after adjusting for
      age, race/ethnicity, body mass index, and education. CONCLUSIONS: Many young
      women engage in unhealthy weight loss behaviors which they may learn online.
      Interventions are needed to instruct young women on safe practices to lose
      weight.

PMID- 21939883
TI  - Randomized controlled trial to compare effects of pain relief during IV insertion
      using bacteriostatic normal saline and 1% buffered lidocaine.
AB  - A major nursing responsibility is to provide patient care and comfort. Pain
      reduction is a component of this responsibility to include preanalgesia for
      peripheral intravenous (IV) insertion. This double-blind randomized controlled
      trial compared differences in the pain level experienced by 56 nurses during IV
      cannulation in each arm; one premedicated with bacteriostatic normal saline (BNS)
      and another with 1% buffered lidocaine (Lido). Subjects and IV inserters were
      blinded to the type of preanalgesia administered during each cannulation.
      Subjects rated pain after each cannulation using a 0 to 10 verbal descriptor
      scale. After IV cannulation was completed in both arms, subjects were asked to
      reflect on which arm, and thus which type of preanalgesia, would be preferred if
      an IV is needed in the future. Sample demographics reflected mean years as
      registered nurse: 18.6+/-10.6 years; mean years in direct care: 7.5+/-4.7 years;
      and mean years experience in inserting IVs: 5.2+/-4.4 years. Significant
      differences were detected between overall BNS and Lido pain scores (2.36+/-1.45
      vs 0.93+/-1.3; P<0.05). Although blinded to the type of preanalgesia used, 89% of
      subjects chose the arm premedicated with Lido. Although statistical differences
      in perceived pain were detected, the pain scores were low and may not be
      clinically significant.

PMID- 21939884
TI  - Surgical cancellations: a review of elective surgery cancellations in a tertiary
      care pediatric institution.
AB  - The purpose of this two-phase quality improvement audit was to analyze elective
      surgery cancellations in a tertiary pediatric care institution and identify and
      recommend nursing practice changes in the preoperative assessment clinic (POAC)
      to potentially influence the overall cancellation rate. A prospective review of
      cancellation data was conducted over a 6-month period in 2008 and again in 2010.
      In both phases of the audit, illness was the leading cause for surgical
      cancellation between the preoperative assessment and the day of surgery, with
      otolaryngology service representing the highest number of cancellations.
      Cancellations at or between the preoperative assessment and the day of surgery
      may be viewed as POAC successes that may have otherwise increased the day-of
      surgery cancellation rate. Educating families on the prevention of illness in the
      perianesthesia period may be a critical nursing role in the prevention of
      surgical cancellations.

PMID- 21939885
TI  - The medicine of music: a systematic approach for adoption into perianesthesia
      practice.
AB  - Patients awaiting surgical procedures often experience anxiety in anticipation of
      events that are uncomfortable, uncertain, and may include a health risk. High
      levels of anxiety result in negative physiological manifestations. Sedatives are
      regularly administered before surgery to reduce patient anxiety. However,
      sedatives often have negative side effects such as drowsiness and respiratory
      depression, and may interact with anesthetic agents, prolonging patient recovery
      and discharge. Therefore, increasing attention is being paid to a variety of
      nonpharmacological interventions for the reduction of preoperative anxiety. Music
      has been used in different medical fields to meet physiological, psychological,
      and spiritual needs of patients. It is a relatively inexpensive modality to
      implement, with low risk of side effects and possible significant benefits. This
      review was conducted with the intent to educate perianesthesia health care
      providers regarding the value of music therapy and provide guidelines for
      implementation, based on a comprehensive review of the literature.

PMID- 21939886
TI  - Educating patients: understanding barriers, learning styles, and teaching
      techniques.
AB  - Health care delivery and education has become a challenge for providers. Nurses
      and other professionals are challenged daily to assure that the patient has the
      necessary information to make informed decisions. Patients and their families are
      given a multitude of information about their health and commonly must make
      important decisions from these facts. Obstacles that prevent easy delivery of
      health care information include literacy, culture, language, and physiological
      barriers. It is up to the nurse to assess and evaluate the patient's learning
      needs and readiness to learn because everyone learns differently. This article
      will examine how each of these barriers impact care delivery along with teaching
      and learning strategies will be examined.

PMID- 21939887
TI  - Implementing preoperative screening of undiagnosed obstructive sleep apnea.

PMID- 21939888
TI  - Tapentadol for multimodal pain management.

PMID- 21939889
TI  - Patient safety outcomes: the importance of understanding the organizational
      culture and safety climate.

PMID- 21939890
TI  - Research news: pediatric patients with sickle cell disease.

PMID- 21939891
TI  - "Novice authors ... what you need to know to make writing for publication
      smooth".

PMID- 21939892
TI  - Registered nurses: are we satisfied with our jobs?

PMID- 21939893
TI  - Making EUReMS count for people with multiple sclerosis.

PMID- 21939894
TI  - Clazosentan for patients with subarachnoid haemorrhage: lessons learned.

PMID- 21939896
TI  - Treatment of restless legs syndrome with rotigotine.

PMID- 21939897
TI  - Patients have their say on research priorities.

PMID- 21939898
TI  - Chris Polman: quietly making multiple sclerosis research tick.

PMID- 21939900
TI  - Collateral blood vessels in acute ischaemic stroke: a potential therapeutic
      target.
AB  - Ischaemic stroke results from acute arterial occlusion leading to focal
      hypoperfusion. Thrombolysis is the only proven treatment. Advanced neuroimaging
      techniques allow a detailed assessment of the cerebral circulation in patients
      with acute stroke, and provide information about the status of collateral vessels
      and collateral blood flow, which could attenuate the effects of arterial
      occlusion. Imaging of the brain and vessels has shown that collateral flow can
      sustain brain tissue for hours after the occlusion of major arteries to the
      brain, and the augmentation or maintenance of collateral flow is therefore a
      potential therapeutic target. Several interventions that might augment collateral
      blood flow are being investigated.

PMID- 21939902
TI  - Critical illness polyneuropathy and myopathy: a major cause of muscle weakness
      and paralysis.
AB  - Critical illness polyneuropathy (CIP) and myopathy (CIM) are complications of
      critical illness that present with muscle weakness and failure to wean from the
      ventilator. In addition to prolonging mechanical ventilation and hospitalisation,
      CIP and CIM increase hospital mortality in patients who are critically ill and
      cause chronic disability in survivors of critical illness. Structural changes
      associated with CIP and CIM include axonal nerve degeneration, muscle myosin
      loss, and muscle necrosis. Functional changes can cause electrical inexcitability
      of nerves and muscles with reversible muscle weakness. Microvascular changes and
      cytopathic hypoxia might disrupt energy supply and use. An acquired sodium
      channelopathy causing reduced muscle membrane and nerve excitability is a
      possible unifying mechanism underlying CIP and CIM. The diagnosis of CIP, CIM, or
      combined CIP and CIM relies on clinical, electrophysiological, and muscle biopsy
      investigations. Control of hyperglycaemia might reduce the severity of these
      complications of critical illness, and early rehabilitation in the intensive care
      unit might improve the functional recovery and independence of patients.

PMID- 21939901
TI  - Management of refractory status epilepticus in adults: still more questions than
      answers.
AB  - Refractory status epilepticus (RSE) is defined as status epilepticus that
      continues despite treatment with benzodiazepines and one antiepileptic drug. RSE
      should be treated promptly to prevent morbidity and mortality; however, scarce
      evidence is available to support the choice of specific treatments. Major
      independent outcome predictors are age (not modifiable) and cause (which should
      be actively targeted). Recent recommendations for adults suggest that the
      aggressiveness of treatment for RSE should be tailored to the clinical situation.
      To minimise intensive care unit-related complications, focal RSE without
      impairment of consciousness might initially be approached conservatively;
      conversely, early induction of pharmacological coma is advisable in generalised
      convulsive forms of the disorder. At this stage, midazolam, propofol, or
      barbiturates are the most commonly used drugs. Several other treatments, such as
      additional anaesthetics, other antiepileptic or immunomodulatory compounds, or
      non-pharmacological approaches (eg, electroconvulsive treatment or hypothermia),
      have been used in protracted RSE. Treatment lasting weeks or months can sometimes
      result in a good outcome, as in selected patients after encephalitis or
      autoimmune disorders. Well designed prospective studies of RSE are urgently
      needed.

PMID- 21939904
TI  - Current challenges in pediatric nutrition. Foreword.

PMID- 21939903
TI  - Exome sequencing: a transformative technology.
AB  - BACKGROUND: Much basic research into disease mechanisms has made use of genetic
      findings to model and understand aetiology. Broad success has been achieved in
      finding disease-linked mutations with traditional positional cloning approaches;
      however, because of the requirements of this method, these successes have been
      limited by the availability of large, well characterised families. Because of
      these and other restrictions the genetic basis of many diseases, and diseases in
      many families, remains unknown. RECENT DEVELOPMENTS: Exome sequencing uses DNA
      enrichment methods and massively parallel nucleotide sequencing to
      comprehensively identify and type protein-coding variants throughout the genome.
      Coupled with growing databases that contain known variants, exome sequencing
      makes identification of genetic mutations and risk factors possible in families
      and samples that were deemed insufficiently informative for previous genetic
      studies. Not only does exome sequencing enable identification of mutations in
      families that were undetectable with linkage and positional cloning methods, but
      compared with these methods, it is also much quicker and cheaper. Use of exome
      sequencing has so far been successful in many rare diseases. WHERE NEXT?: Exome
      sequencing is being adopted widely and we can expect an abundance of mutation
      discovery, similar to the deluge of genome-wide-association findings reported
      over the past 5 years; it is expected to enable the discovery of not only rare
      causal variants, but also protein-coding risk variants. This method will have
      application in both the research and clinical arenas and sets the scene for the
      use of whole-genome sequencing.

PMID- 21939905
TI  - Current challenges in pediatric nutrition. Introduction.

PMID- 21939906
TI  - Current challenges in pediatric nutrition.
AB  - In pediatric nutrition the most important overall theme is breastfeeding. While
      there is no alternative in most mammals--and offspring would die if the mother
      had no milk or could not feed the newborn--human mothers were offered alternative
      ways of infant feeding. Today restoring breastfeeding is a major goal for
      pediatricians, midwifes, and lactation advisers. Feeding the premature baby and
      adding long chain fatty acids and prebiotics to formula is an area of growing
      interest. Undernutrition is a special challenge for nutritional care because even
      in recent years severely undernourished children die of inadequate management
      with too much volume and too much protein in the initial phase. Much knowledge
      has been gained about parenteral nutrition for children with gut failure. Even
      children with very short bowel length at birth have a good prognosis and can
      often achieve enteral adaptation. New solutions for parenteral nutrition, new
      materials, and new care concepts have been identified. Problems considered
      inherent to parenteral nutrition are widely preventable.

PMID- 21939907
TI  - Benefits from longer breastfeeding: do we need to revise the recommendations?
AB  - The evidence is well established that breastfeeding results in a reduction of
      certain health risks. Debate has arisen, however, about the optimal duration of
      exclusive breastfeeding. The general recommendation is to breastfeed newborn
      babies for 6 months exclusively and then to introduce complementary foods and
      continue breastfeeding. In industrialized countries, earlier introduction of
      complementary foods is recommended for preventing food allergy. There are data
      suggesting such a risk reduction and therefore the argument must be taken
      seriously. Considering the evidence about earlier introduction of complementary
      foods, it remains unclear how long the children have been exclusively and
      partially breastfed. It may well be that children who are breastfed exclusively
      for 3 months or less benefit from an introduction of complementary foods as long
      as they still receive partial breastfeeding. If this is true, it remains the
      first priority to advertise for longer breastfeeding, and only if this fails, the
      mothers may be advised to introduce complementary foods at a time when they still
      breastfeed.

PMID- 21939908
TI  - Nutrition and celiac disease.
AB  - Celiac disease affects about 1% of the European and North American population.
      The classical clinical presentation is with symptoms of malabsorption. Serologic
      studies demonstrate that most celiac patients present with oligosymptomatic
      (silent), latent, potential, and extraintestinal forms. The disease is defined as
      an immune-mediated systemic disorder of genetically disposed individuals (HLA
      DQ2/8) induced by the alcohol-soluble fractions of cereals and characterized by
      gluten-dependent symptoms, celiac-specific antibodies (against tissue
      transglutaminase 2), and a Marsh 2-3 enteropathy. In the last 60 years, a strict
      and lifelong gluten-free diet has been demonstrated to be effective and safe,
      preventing most potential complications of the disease, including autoimmune
      disease, osteoporosis, infertility, prematurity, and malignancy. Among patients
      with celiac disease, the toxicity of oats seems to be less than wheat, barley,
      and rye. The introduction of oats into the diet of patients with celiac disease
      should increase taste, fiber content, diversity, compliance with the diet, and
      quality of life. The clinical studies provide limited results in favor of a
      general harmlessness of oats for celiac disease patients. Patients with celiac
      disease who consume oats (20-25 g/d for children, 50-70 g/d for adults) need
      proper follow-up.

PMID- 21939909
TI  - The role of nutrition in the etiology of inflammatory bowel disease.
AB  - Many foods have been implicated in theories about the etiology of inflammatory
      bowel disease. While evidence has accumulated that nutritional factors as part of
      overall lifestyle changes may play a role in the growing incidence, no specific
      dietary recommendations except the promotion of breastfeeding can currently be
      given to decrease the risk of developing Crohn's disease or ulcerative colitis.
      For the treatment of Crohn's disease in children and adolescents, however,
      enteral feeding with a semi-elemental diet seems to be as effective as
      corticosteroids in inducing and maintaining remission. In the meta-analyses,
      advantages of one formula over the other are evened out, and more research is
      warranted into the anti-inflammatory properties of different nutrients, such as
      polyunsaturated fatty acids, butyrate, glutamine, and cytokines, such as
      transforming growth factors-beta. Unfortunately, for practical reasons,
      nutritional therapy remains underutilized, even though pediatric patients are
      most vulnerable to the harmful effects of nutrient deficiencies on growth,
      pubertal development, and bone health. There is hope that in the future the new
      field of nutrigenomics may enable physicians to more accurately tailor a specific
      diet to the patient genotype.

PMID- 21939910
TI  - Diagnosing anemia in inflammatory bowel disease: beyond the established markers.
AB  - The main types of anemia in inflammatory bowel disease (IBD) are iron deficiency
      anemia (IDA) and anemia of inflammatory etiology, or anemia of chronic disease
      (ACD). In the management of IBD patients with anemia it is essential for the
      physician to diagnose the type of anemia in order to decide in an evidence-based
      manner for the appropriate treatment. However, the assessment of iron status in
      IBD in many cases is rather difficult due to coexistent inflammation. For this
      assessment several indices and markers have been suggested. Ferritin, seems to
      play a central role in the definition and diagnosis of anemia in IBD and
      transferrin, transferrin saturation (Tsat), and soluble transferrin receptors are
      also valuable markers. All these biochemical markers have several limitations
      because they are not consistently reliable indices, since they are influenced by
      factors other than changes in iron balance. In this review, in addition to them,
      we discuss the newer alternative markers for iron status that may be useful when
      serum ferritin and Tsat are not sufficient. The iron metabolism regulators,
      hepcidin and prohepcidin, are still under investigation in IBD. Erythrocytes
      parameters like the red cell distribution width (RDW) and the percentage of
      hypochromic red cells as well as reticulocyte parameters such as hemoglobin
      concentration of reticulocytes, red blood cell size factor and reticulocyte
      distribution width could be useful markers for the evaluation of anemia in IBD.

PMID- 21939911
TI  - Environmental factors in infancy and ulcerative colitis in the Central South of
      Chile: a case-control study.
AB  - BACKGROUND AND AIMS: Evidence for the role of the hygiene hypothesis and the
      development of Ulcerative Colitis (UC) is unclear. We aimed to explore the
      association between environmental factors in infancy and UC. METHODS: A hospital
      based case-control study (52 UC cases, response: 77%, 174 age- , sex and place of
      living matched controls, response: 62%) was carried out in the Central South of
      Chile in 2009/2010. Patients or parents underwent a personal interview about
      early life experiences. RESULTS: High paternal education (adjusted Odds Ratio
      (aOR): 2.1; 95% CI: 1.0-4.5) as proxy for socioeconomic status was positively
      associated with case status in the final multivariate logistic regression model.
      Likewise, having older siblings was a risk factor for UC (aOR: 2.2; 95%CI: 1.1.
      4.4). CONCLUSIONS: The importance for some early life environmental factors in
      the development of UC was established. However, the role of the hygiene
      hypothesis could not be confirmed for all environmental factors.

PMID- 21939912
TI  - Methotrexate in ulcerative colitis: a Spanish multicentric study on clinical use
      and efficacy.
AB  - BACKGROUND: Few data are available on the efficacy of methotrexate (MTX) in
      ulcerative colitis (UC). AIM: To evaluate the efficacy and safety of MTX in UC
      patients. PATIENTS AND METHODS: UC patients who had been treated with MTX were
      identified from the databases of 8 Spanish IBD referral hospitals. Patients were
      included in the study if they received MTX for steroid dependency or steroid
      refractoriness. Therapeutic success was defined as the absence of UC-related
      symptoms, complete steroid withdrawal and no requirement of rescue therapies
      within the first 6 months after starting MTX. RESULTS: Forty patients were
      included, 70% treated for steroid dependency and 27% for steroid refractoriness.
      Thiopurines had been previously attempted in 87.5% of patients. The median dose
      of MTX used for induction was 25mg (IIQ 17.5-25) weekly given parenterally in
      82.5% of cases. Eighty-five percent of patients were on steroids when MTX was
      started. Forty-five percent of patients met criteria for therapeutic success.
      Initial treatment failures were mainly due to inefficacy (50%) or intolerance
      (36%). After a median follow-up of 28 months (IQR 22-47), 38% of patients with
      initial therapeutic success required new steroid courses, 22% started biological
      therapy, and only 1 patient required colectomy. The cumulative probability of
      maintaining steroid-free clinical remission was 60%, 48%, and 35% at 6, 12, and
      24 months after starting MTX, respectively. Eleven patients (27.5%) experienced
      adverse events, leading to MTX discontinuation in only 8 of them. CONCLUSIONS:
      MTX appears to be effective to maintain clinical remission in UC, at least in the
      short-term, with an acceptable safety profile.

PMID- 21939913
TI  - Serum levels of soluble receptor for advanced glycation endproducts (sRAGE) are
      higher in ulcerative colitis and correlate with disease activity.
AB  - Interaction of the receptor for advanced glycation endproducts (RAGE) with its
      ligands results in expression of inflammatory mediators, activation of NF-kappaB,
      and induction of oxidative stress, all of which have been implicated in the
      pathogenesis of inflammatory bowel diseases (IBD). Soluble receptor for advanced
      glycation endproducts (sRAGE) has recently emerged as a reliable biomarker of
      inflammation in numerous RAGE-mediated disorders. OBJECTIVE: To assess sRAGE
      levels in adult patients with IBD. METHOD: Serum was collected from adult
      patients with Crohn's disease (CD, 56 patients), ulcerative colitis (UC, 60
      patients), and healthy controls (HC, 113 subjects). Levels of sRAGE were
      determined by enzyme-linked immunosorbent assay. RESULTS: Serum sRAGE levels were
      elevated in IBD compared to HC and were higher in UC patients compared to CD and
      HC. Levels of sRAGE were significantly higher in the serum of UC patients with
      active disease compared to patients with inactive disease, but no association
      with the Montreal Classification was evident. Serum sRAGE was lower in CD
      patients with biological therapies. CONCLUSIONS: These findings suggest that
      serum levels of sRAGE are altered in patients with intestinal inflammation and
      may reflect distinct immunoinflammatory pathogenesis of UC and CD.

PMID- 21939914
TI  - Sexual function after failed ileal pouch-anal anastomosis.
AB  - BACKGROUND AND AIMS: Failure of ileal pouch-anal anastomosis (IPAA) occurs in
      around 10% of the patients. Compared to patients with functioning pouches, health
      related quality of life is deteriorated after failure. Sexual function in
      patients with pouch failure is however poorly studied. The aim was to study
      sexual function in patients with pelvic pouch failure; patients with functioning
      pouches were used as controls. The hypothesis was that patients with pouch
      failure have worse sexual function. METHODS: 36 patients with pouch failure were
      compared with 72 age and sex-matched controls with ulcerative colitis and
      functioning pouches. The patients answered a set of questionnaires concerning
      sexual function (Female Sexual Function Index [FSFI] and International Index of
      Erectile Function [IIEF]), body image (BIS-scale) and health-related quality of
      life (SF-36). RESULTS: Both women and men with pouch failure scored lower than
      controls in the FSFI and IIEF questionnaires. However, none of the observations
      were statistically significant. The scores in the failure group (for both sexes)
      were below the cut-off level for sexual dysfunction. Scores for the BIS
      instrument were significantly lower for both sexes in the failure group. Women
      and men in the failure group scored lower than the controls in all domains of the
      SF-36, however statistically significant only for the social function domain in
      men. CONCLUSIONS: The hypothesis, that a failed IPAA is associated with worse
      sexual function, was not confirmed. Compared to patients with functioning
      pouches, patients with pouch failure have inferior body image.

PMID- 21939915
TI  - Influence of ileal pouch anal anastomosis on bone loss in ulcerative colitis
      patients.
AB  - BACKGROUND AND AIM: Patients with ulcerative colitis (UC) are at an increased
      risk for low bone mineral density (BMD). It is unclear whether proctocolectomy
      with ileal pouch-anal anastomosis (IPAA) for UC alters the risk of bone loss. The
      aim of this study was to compare BMD in UC patients with and without IPAA.
      METHODS: A total of 267 patients with UC and IPAA (study group) were compared to
      119 UC patients without IPAA (control group) in this cross-sectional study. The
      demographic and clinical variables including dual-energy X-ray absorptiometry
      scan results were compared. Patients were classified as having normal or low BMD,
      based on the criteria by the International Society for Clinical Densitometry.
      Univariate and multivariate analyses were performed to assess risk factors
      associated with low BMD. Age, gender, race, smoking status, steroid use, alcohol
      use, body mass index, years of absent estrogen protection, use of calcium,
      vitamin D supplements and disease duration were selected as covariates. RESULTS:
      83 (31.1%) had low BMD in the study group vs. 18 (15.1%) in the control group
      (p=0.001). 2/13 (15.4%) had low BMD before surgery. The mean age of patients in
      the study and control groups were 44.7 +/- 14.1 vs. 52.4 +/- 17.7 years,
      respectively (p<0.001). The hip BMD was lower in the study group (0.93 +/- 0.17
      g/cm2) than that in the control group (0.98 +/- 0.17 g/cm2) (p=0.038). Fragility
      fracture was documented in 23 (8.6%) patients in the study group vs. 3 (2.5%) in
      the control group (p=0.038) Sixty-four (24.0%) of the study group patients were
      using corticosteroids after surgery in contrast to 93 (78.2%) in the control
      group (p<0.001). On multivariable analyses, covariate adjusted factors associated
      with a low BMD in UC patients were advanced age [odds ratio (OR) 1.51 per 5
      years; 95% confidence interval [CI], 1.34-1.71], low body mass index (OR=2.37 per
      5 kg/m(2) decrease; 95% CI, 1.68-3.36), and the presence of IPAA (OR=6.02; 95%
      CI, 2.46-14.70). For the 13 IPAA patients who had information available, BMD
      before IPAA was low. After a median of 46 (Range 7-84) months after IPAA, BMD
      improved in 7/13 patients (53.8%), while it continued to be low in 6/13 (46.2%)
      patients. CONCLUSIONS: Low BMD is common in patients with UC. The risk appears to
      persist even after colectomy and IPAA surgery suggesting that these patients need
      to be monitored for bone loss.

PMID- 21939916
TI  - C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) or both? A
      systematic evaluation in pediatric ulcerative colitis.
AB  - BACKGROUND: There has not been an extensive comparison of CRP and ESR in
      ulcerative colitis (UC), and thus, we aimed to explore their utility in UC.
      METHODS: Four previously enrolled cohorts of 451 children with UC were utilized,
      all including laboratory, clinical and endoscopic data. A longitudinal analysis
      was performed on prospectively collected data of 75 children. Disease activity
      was captured by both global assessment and pediatric UC activity index (PUCAI).
      RESULTS: The best thresholds to differentiate quiescent, mild, moderate and
      severe disease activity, were <23, 23-29, 30-37, >37 mm/h for ESR, and <2.5, 2.5
      5, 5.01-9, >9 mg/L for CRP (area under the ROC curves 0.70-0.81). Correlation of
      endoscopic appearance with CRP and ESR were 0.55 and 0.41, respectively
      (P<0.001). Both CRP and ESR may be completely normal in 34% and 5-10% of those
      with mild and moderate-severe disease activity, respectively. Elevated CRP in the
      presence of normal ESR or vice versa was noted in 32%, 38%, 30% and 17% of those
      with quiescent, mild, moderate and severe disease activity. Over time, the
      utility of CRP and ESR in reflecting disease activity remained stable in 70-80%
      of cases. CONCLUSION: In ~2/3 of children, both CRP and ESR values reflect
      disease activity to a similar degree and in the remaining, either CRP or ESR may
      be sufficient, with slight superiority of CRP. CRP is more closely correlated
      with endoscopic appearance. When either CRP or ESR performs well for a given
      patient, this is likely to remain so over time. Therefore, it may not be
      justified to routinely test both ESR and CRP in monitoring disease activity.

PMID- 21939917
TI  - Cancer in inflammatory bowel disease 15 years after diagnosis in a population
      based European Collaborative follow-up study.
AB  - AIM OF THE STUDY: To determine the occurrence of intestinal and extraintestinal
      cancers in the 1993-2009 prospective European Collaborative Inflammatory Bowel
      Disease (EC-IBD) Study Group cohort. PATIENTS-METHODS: A physician per patient
      form was completed for 681 inflammatory bowel disease patients (445UC/236CD) from
      9 centers (7 countries) derived from the original EC-IBD cohort. For the 15-year
      follow up period, rates of detection of intestinal and extraintestinal cancers
      were computed. RESULTS: Patient follow-up time was fifteen years. In total 62/681
      patients (9.1%) [41 with ulcerative colitis/21 with Crohn's disease, 36 males/26
      females] were diagnosed with sixty-six cancers (four patients with double
      cancers). Colorectal cancer was diagnosed in 9/681 patients [1.3%] (1 Crohn's
      disease and 8 ulcerative colitis). The remaining 53 cancers were extraintestinal.
      There was a higher prevalence of intestinal cancer in the Northern centers
      compared to Southern centers [p=NS]. Southern centers had more cases of
      extraintestinal cancer compared to Northern centers [p=NS]. The frequency of all
      observed types of cancers in Northern and in Southern centers did not differ
      compared to the expected one in the background population. CONCLUSIONS: In the
      fifteen-year follow up of the EC-IBD Study Group cohort the prevalence of cancer
      was 9.1% with most patients having a single neoplasm and an extraintestinal
      neoplasm. In Northern centers there were more intestinal cancers while in
      Southern centers there were more extraintestinal cancers compared to Northern
      centers. In this IBD cohort the frequency of observed cancers was not different
      from that expected in the background population.

PMID- 21939918
TI  - Nutritional problems in inflammatory bowel disease: the patient perspective.
AB  - BACKGROUND AND AIMS: Crohn's Disease (CD) and ulcerative colitis (UC) are
      inflammatory bowel diseases (IBD), which may result in nutrition problems that
      impact on patient health, nutritional status and quality of life. Subjective
      reports of how IBD patients experience these problems as part of their disease
      process, including comparisons between patient groups, or the need for tailored
      nutrition advice as perceived by these patients, have not been widely studied.
      This survey aimed to identify and explore nutritional problems that are important
      to CD and UC patients and to investigate their views on the IBD health services
      provided to help them with these. METHODS: Eighty-seven IBD patients were invited
      to take part in a nutrition survey using face-to-face questionnaire interviews.
      The survey asked about food and nutrition problems that patients have
      experienced, identifying which were most significant and the extent to which they
      had been addressed by the clinical service. RESULTS: Seventy-two IBD patients
      completed the evaluation (47 CD, 25 UC). Of these, 45 (62.5%) felt that food and
      nutrition were either 'important' or 'extremely important' in their experience of
      IBD, and 59 (82%) reported problems with food and nutrition. Patients with CD and
      UC reported similar frequencies of most nutritional problems. However, 44 (94%)
      CD vs. 16 (64%) UC patients reported problems with weight (p=0.002). Less than
      half of patients had seen a dietitian for tailored nutritional advice to address
      these problems. CONCLUSIONS: Nutritional problems experienced and reported by IBD
      patients are numerous and varied. They are considered important by patients with
      CD and UC, both of whom would generally value specific dietary counselling,
      highlighting a need for further research in this area and adequate and equal
      provision of services for both groups.

PMID- 21939919
TI  - IgG4-associated ampullitis and cholangiopathy in Crohn's disease.
AB  - Inflammatory bowel disease (IBD) is reported to be associated with autoimmune
      pancreatitis and IgG4-related sclerosing disease. We report a case of a 28 year
      old African American male with a long history of upper gastrointestinal tract
      Crohn's disease (CD) with multiple surgeries who developed medically refractory
      disease with small bowel obstruction. He had abnormal liver function tests with
      imaging evidence of chronic pancreatitis and ampullary inflammatory process. He
      underwent Whipple's procedure. Histopathological evaluation of surgical specimens
      of the ampulla and distal common bile duct showed accumulation of IgG4-positive
      plasma cells in the lamina propria. Preoperative endoscopic biopsies also showed
      chronic active enteritis involving the duodenum and jejunum with increased IgG4
      expressing plasma cell infiltration. His serum IgG4 was 164 mg/dL. The
      association of IgG4-expressing plasma cell accumulation in the gastrointestinal
      tract with IBD in patients with hepatobiliary manifestation may have
      pathogenetic, diagnostic and therapeutic implications.

PMID- 21939920
TI  - Stevens-Johnson syndrome with sulfasalazine treatment: report of two cases.
AB  - We report two cases of Stevens-Johnson syndrome (SJS) associated with the use of
      sulfasalazine in two ulcerative colitis patients previously tolerant to
      mesalamine. SJS and toxic epidermal necrolysis (TEN) are very rare adverse
      cutaneous reactions that can be associated with the use of sulfasalazine. The
      most severe cases can result in death, and for the others, permanent skin,
      mucosal or ocular sequelae, which can impair the quality of life in our young IBD
      patients. Clinicians and patients need to be aware of the signs and symptoms that
      often precede the appearance of the mucocutaneous lesions in a SJS or TEN, such
      as fever, influenza-like symptoms, sore throat or burning eyes. For patients with
      SJS or TEN, immediate withdrawal of the offending medication should be done when
      blisters or erosions appear in the course of a drug eruption, as this may improve
      the prognosis.

PMID- 21939921
TI  - Concurrent small bowel adenocarcinoma and carcinoid tumor in Crohn's disease-
      case report and literature review.
AB  - Adenocarcinomas of the large and small bowel, as well as intestinal carcinoid
      tumors have been reported at increased rates in Crohn's disease. We herein report
      a rare case of concurrent adenocarcinoma and carcinoid tumor of the small bowel
      presenting as intestinal obstruction and found incidentally at laparotomy in a 55
      year old male with longstanding ileal Crohn's disease. We performed a Medline
      Pubmed search for cases of synchronous or composite adenocarcinoma and carcinoid
      tumor in the setting of Crohn's disease and identified four similar cases.
      Concurrent adenocarcinoma and carcinoid tumor occurred both in newly diagnosed
      and longstanding Crohn's disease, most commonly involved the terminal ileum and
      presented with symptoms mimicking Crohn's disease. Diagnosis was made
      incidentally at laparotomy in all cases. Lymph node involvement was variable.
      Clinicians should be aware of this rare entity for expeditious surgical
      intervention.

PMID- 21939922
TI  - Fulminant ulcerative colitis despite maximal immunosuppression following liver
      transplantation: a case report and literature review.
AB  - Inflammatory Bowel Disease (IBD) is thought to be the result of an overly
      aggressive immune response to ubiquitous antigens. Immuno -modulation and 
      suppression is therefore currently the treatment of choice. It was long
      anticipated that the course of pre-existing IBD should improve after orthotopic
      liver transplantation (OLT) due to increased immunosuppression. We report the
      case of a patient who developed acute fulminant colitis despite triple
      immunosuppression and mesalazine and review the relevant literature.

PMID- 21939923
TI  - Cytomegalovirus disease, haemophagocytic syndrome, immunosuppression in patients
      with IBD: 'a cocktail best avoided, not stirred'.
AB  - We report two cases of cytomegalovirus (CMV) viraemia resulting in severe
      pneumonitis and associated haemophagocytic syndrome manifesting in patients with
      inflammatory bowel disease, on stable doses of azathioprine in clinical
      remission. In both cases, azathioprine was withdrawn at time of hospital
      presentation and after delays in diagnosis; intravenous ganciclovir was then
      administered, with resultant rapid improvement of haematological and clinical
      parameters. Following recovery, immunomodulators were not recommenced given
      patient aversion and the theoretical risk of CMV reactivation, albeit the
      evidence for this approach is limited. CMV-related haemophagocytic syndrome and
      organ dysfunction, in the context of immunomodulator therapy in IBD are rare but
      life-threatening, and thus requires further investigation and discussion.

PMID- 21939924
TI  - Comprehensive MRI diagnosis of sacral osteomyelitis and multiple muscle abscesses
      as a rare complication of fistulizing Crohn's disease.
AB  - Pelvic osteomyelitis is a very uncommon complication of Crohn's disease, usually
      clinically unsuspected in the setting of acute Crohn's disease relapses. The case
      of a 21-year old patient is reported, in whom ileo-cecal inflammatory disease was
      complicated by fistulization to the presacral space and sacral osteomyelitis,
      plus multiple abscesses involving the iliopsoas, posterior paravertebral and
      gluteal muscles. As confirmed by surgical and pathological findings, MRI provided
      comprehensive imaging diagnosis by demonstrating both the pathogenesis and the
      full extent of the complex, deep pelvic inflammatory process. Low back pain in
      patients with Crohn's disease should not be underestimated since its differential
      diagnosis includes serious and potentially life-threatening causes such as
      osteomyelitis, so prompt assessment with cross sectional imaging, particularly
      MRI, is necessary.

PMID- 21939925
TI  - Results from the 2nd Scientific Workshop of the ECCO. I: Impact of mucosal
      healing on the course of inflammatory bowel disease.
AB  - Over the past years, mucosal healing has emerged as a major therapeutic goal in
      clinical trials in inflammatory bowel diseases. Accumulating evidence indicates
      that mucosal healing may change the natural course of the disease by decreasing
      the need for surgery and reducing hospitalization rates in both ulcerative
      colitis and Crohn's disease. Mucosal healing may also prevent the development of
      long-term disease complications, such as bowel damage in Crohn's disease and
      colorectal cancer in ulcerative colitis. Histologic healing may be the ultimate
      therapeutic goal in ulcerative colitis, whereas its impact on the course of
      Crohn's disease is unknown. Complete mucosal healing may be required before
      considering drug withdrawal. Targeting early Crohn's disease is more effective
      than approaches aimed at healing mucosa in longstanding disease. Several
      questions remain to be answered: should mucosal healing be systematically used in
      clinical practice? Should we optimize therapies to achieve mucosal healing? What
      is the degree of intestinal healing that is required to change the disease
      course? Large prospective studies addressing these issues are needed.

PMID- 21939927
TI  - In-vitro dissolution testing of 5-aminosalicylic acid release from pH dependent
      mesalazine formulations.

PMID- 21939926
TI  - Results of the 2nd part Scientific Workshop of the ECCO. II: Measures and markers
      of prediction to achieve, detect, and monitor intestinal healing in inflammatory
      bowel disease.
AB  - The healing of the intestine is becoming an important objective in the management
      of inflammatory bowel diseases. It is associated with improved disease outcome.
      Therefore the assessment of this healing both in clinical studies and routine
      practice is a key issue. Endoscopy for the colon and terminal ileum and
      computerized tomography or magnetic resonance imaging for the small bowel are the
      most direct ways to evaluate intestinal healing. However, there are many unsolved
      questions about the definition and the precise assessment of intestinal healing
      using these endoscopic and imaging techniques. Furthermore, these are relatively
      invasive and expensive procedures that may be inadequate for regular patients'
      monitoring. Therefore, biomarkers such as C-reactive protein and fecal
      calprotectin have been proposed as surrogate markers for intestinal healing.
      Nevertheless, the sensitivity and specificity of these markers for the prediction
      of healing may be insufficient for routine practice. New stool, blood or
      intestinal biomarkers are currently studied and may improve our ability to
      monitor intestinal healing in the future.

PMID- 21939929
TI  - Piercing and Crohn's disease.

PMID- 21939930
TI  - On the usefulness of small bowel capsule endoscopy in Crohn's disease.

PMID- 21939931
TI  - Cigarette smoking in Crohn's disease: can we do more?

PMID- 21939932
TI  - A case of ulcerative colitis co-existing with pseudo-membranous enterocolitis.

PMID- 21939933
TI  - Fundamental wire technique and current standard strategy of percutaneous
      intervention for chronic total occlusion with histopathological insights.
AB  - Currently, successful treatment of chronic total occlusion (CTO) seems markedly
      improved, due to several new techniques and dedicated device developments.
      However, this improved success rate is often limited to procedures performed by
      skilled, highly experienced operators. To improve the overall success rate of
      percutaneous coronary intervention of CTO from a worldwide perspective, a deeper
      understanding of CTO histopathology might offer insights into the development of
      new techniques and procedural strategies. In this review, CTO histopathology and
      wire techniques are discussed on the basis of the fundamental concepts of
      antegrade and retrograde approaches. Although details pertaining to wire
      manipulation are very difficult to explain objectively, we tried to describe this
      as best as possible in this article. Finally, a systematic review of the current
      standard CTO strategy is provided. Hopefully, this article will enhance the
      understanding of this complex procedure and, consequently, promote safe and
      effective CTO-percutaneous coronary intervention for patients who present with
      this challenging lesion subset.

PMID- 21939934
TI  - Long-term outcome of percutaneous coronary intervention for chronic total
      occlusions.
AB  - OBJECTIVES: The aim of this study was to evaluate long-term clinical outcomes
      after percutaneous coronary intervention (PCI) for chronic total occlusions
      (CTO). BACKGROUND: Despite technical advancements, there is a paucity of data on
      long-term outcomes after PCI of CTO. METHODS: We evaluated long-term clinical
      outcomes in 1,791 patients who underwent PCI of 1,852 CTO at 3 tertiary care
      centers in the United States, South Korea, and Italy between 1998 and 2007.
      Median follow-up was 2.9 years (interquartile range: 1.5 to 4.6 years). RESULTS:
      Procedural success was obtained in 1,226 (68%) patients. Stents were implanted in
      1,160 patients (95%); 396 patients (34%) received bare-metal stents (BMS), and
      764 patients (66%) received drug-eluting stents (DES). After multivariable
      analysis, successful CTO PCI was an independent predictor of a lower cardiac
      mortality (hazard ratio [HR]: 0.40, 95% confidence interval [CI]: 0.21 to 0.75, p
      < 0.01) and reduced need for coronary artery bypass graft surgery (HR: 0.21, 95%
      CI: 0.13 to 0.40, p < 0.01); it also correlated with a strong trend toward lower
      all-cause mortality (HR: 0.63, 95% CI: 0.40 to 1.00, p = 0.05) at 5-year follow
      up. Among patients who underwent stent implantation, treatment with DES rather
      than BMS resulted in less target vessel revascularization at long-term follow-up
      (17.2% vs. 31.1%, p < 0.01); definite/probable stent thrombosis rates were
      similar (DES 1.7%, BMS 2.3%, p = 0.58). Within the DES subgroup, patients treated
      with paclitaxel-eluting stents and sirolimus-eluting stents had similar clinical
      outcomes. CONCLUSIONS: Successful CTO PCI is associated with reduced long-term
      cardiac mortality and need for coronary artery bypass graft surgery. Treatment of
      CTO with DES rather than BMS is associated with a significant reduction in target
      vessel revascularization with similar rates of stent thrombosis. Paclitaxel
      eluting stents and sirolimus-eluting stents had similar long-term safety and
      efficacy outcomes.

PMID- 21939935
TI  - Chronic total coronary occlusion percutaneous intervention the case for
      randomized trials.

PMID- 21939936
TI  - Long-term safety and effectiveness of drug-eluting stents for the treatment of
      saphenous vein grafts disease: a population-based study.
AB  - OBJECTIVES: The purpose of this study was to evaluate the long-term safety and
      effectiveness of drug-eluting stents (DES) for the treatment of saphenous vein
      graft (SVG) disease. BACKGROUND: DES are frequently implanted for SVG
      interventions, but some studies have shown that they are not effective in
      reducing target vessel revascularization (TVR) over longer-term follow-up. Some
      studies suggest there is increased mortality with DES compared with bare-metal
      stents (BMS). METHODS: We performed propensity score matching analysis using a
      population-based cohort that included 709 well-matched pairs (n = 1,418) who
      received DES or BMS for the treatment of SVG disease from 2003 to 2008. Outcomes
      of interest included repeat TVR, myocardial infarction, and death. RESULTS: The
      mean age of the propensity-matched cohort was 69 years, 50% had diabetes, and the
      mean age of SVG was 10.6 years. At 4-year follow-up, the rate of repeat TVR was
      21% in the DES group and 27.6% in the BMS group (p = 0.004). DES implantation was
      associated with the largest TVR reduction among patients with diabetes and
      patients receiving longer stents (>=30 mm) and the number of procedures needed to
      prevent a TVR at 4 years was 8 and 7, respectively. The composite rate of
      myocardial infarction or death was not significantly different between DES and
      BMS at 4 years (27.8% vs. 32.6%, p = 0.09). CONCLUSIONS: Implantation of DES in
      the treatment of SVG disease is associated with substantial reduction of repeat
      revascularization, without evidence of an increased risk of myocardial infarction
      or death at longer-term follow-up.

PMID- 21939937
TI  - Impact of intravascular ultrasound imaging on early and late clinical outcomes
      following percutaneous coronary intervention with drug-eluting stents.
AB  - OBJECTIVES: This study sought to assess the impact of intravascular ultrasound
      (IVUS)-guided versus angiography-guided drug-eluting stent (DES) implantation.
      BACKGROUND: There are limited data on IVUS guidance in the DES era. Therefore, we
      investigated the impact of IVUS guidance on clinical outcomes in the MATRIX
      (Comprehensive Assessment of Sirolimus-Eluting Stents in Complex Lesions)
      registry. METHODS: The MATRIX registry prospectively enrolled consecutive,
      unselected patients treated with sirolimus-eluting stents (SES) (n = 1,504); 631
      patients (42%) underwent IVUS-guided stenting, and 873 (58%) had only
      angiographic guidance. We assessed 30-day, 1-year, and 2-year rates of
      death/myocardial infarction (MI), major adverse cardiac events (cardiac death,
      MI, or target vessel revascularization), and definite/probable stent thrombosis
      in 548 propensity-score matched patient pairs. RESULTS: After matching, baseline
      and angiographic characteristics were similar in IVUS and no-IVUS groups.
      Patients in the IVUS group had significantly less death/MI at 30 days (1.5% vs.
      4.6%, p < 0.01), 1 year (3.3% vs. 6.5%, p < 0.01), and 2 years (5.0% vs. 8.8%, p
      < 0.01). Patients in the IVUS group had significantly less major adverse cardiac
      events at 30 days (2.2% vs. 4.8%, p = 0.04) and numerically less major adverse
      cardiac events at 1 year (9.1% vs. 13.5%, p = 0.07) and 2 years (12.9% vs. 16.7%,
      p = 0.18). Rates of MI were significantly lower in the IVUS group at 30 days
      (1.5% vs. 4.0%, p < 0.01), 1 year (1.8% vs. 4.8%, p < 0.01), and 2 years (2.1%
      vs. 5.7%, p < 0.01). CONCLUSIONS: IVUS-guided stent implantation appears to be
      associated with a reduction in both early and long-term clinical events. Further
      investigation in randomized controlled trials is warranted.

PMID- 21939938
TI  - Sirolimus-eluting coronary stents in octogenarians: a 1-year analysis of the
      worldwide e-SELECT Registry.
AB  - OBJECTIVES: The aim of this study was to identify the worldwide practice of
      Cypher Select (Cordis Corporation, Bridgewater, New Jersey) or Cypher Select Plus
      sirolimus-eluting stent (SES) in patients 80 years of age (octogenarian) and to
      identify clinical outcomes in this patient population. BACKGROUND: The use of
      drug-eluting stents in elderly patients may have different features compared with
      younger patients. METHODS: Between 2006 and 2008, 15,147 patients from 320
      hospitals in 56 countries were enrolled in a registry. Initial implantation and
      follow-up outcome information obtained at 1-year follow-up in 675 octogenarian
      patients were compared with those in 14,472 nonoctogenarian patients. RESULTS:
      Octogenarians had significantly more comorbidities and had higher Charlson
      comorbidity index scores (1.5 +/- 1.6 vs. 1.0 +/- 1.3, p < 0.001). Rates of
      cardiac death (3.3% vs. 0.9%, p < 0.001), myocardial infarction (2.3% vs. 1.9%, p
      = 0.021), and definite or probable stent thrombosis (2.3% vs. 0.9%, p = 0.0002),
      and major bleeding (2.0% vs. 0.9%, p = 0.015) were significantly higher in
      octogenarians at 1 year; however, there was no significant difference in the rate
      of target lesion revascularization between the 2 groups (3.2% vs. 2.2%, p =
      0.12). In octogenarians, a high Charlson comorbidity index was an independent
      predictor of death and stent thrombosis up to 360 days from the index procedure
      (hazard ratio: 1.3, 95% confidence interval: 1.1 to 1.5, p < 0.001, and hazard
      ratio: 1.5, 95% confidence interval: 1.3 to 1.8, p < 0.001, respectively).
      CONCLUSIONS: Stenting with SES may be an effective therapeutic option in elderly
      patients, with acceptable rates of complications and a very low rate of repeat
      revascularization as demonstrated by this e-SELECT (A Multi-Center Post-Market
      Surveillance Registry) subgroup analysis.

PMID- 21939939
TI  - Serial analysis of the malapposed and uncovered struts of the new generation of
      everolimus-eluting bioresorbable scaffold with optical coherence tomography.
AB  - OBJECTIVES: The aim of this study is to assess the serial changes in strut
      apposition and coverage of the bioresorbable vascular scaffolds (BVS) and to
      relate this with the presence of intraluminal masses at 6 months with optical
      coherence tomography (OCT). BACKGROUND: Incomplete strut/scaffold apposition
      (ISA) and uncovered struts are related to a higher risk of scaffold thrombosis.
      Bioresorbable vascular scaffolds can potentially avoid the risk of scaffold
      thrombosis because of its complete resorption. However, during the resorption
      period, the risk of scaffold thrombosis is unknown. METHODS: OCT was performed in
      25 patients at baseline and 6 months. Struts were classified according to
      apposition, coverage, and presence of intraluminal masses. Persistent ISA was
      defined as malapposed struts present at baseline and follow-up, and late acquired
      ISA as ISA developing at follow-up, and scaffold pattern irregularities when the
      strut distribution suggested scaffold fracture. RESULTS: At baseline, 3,686
      struts were analyzed: 128 (4%) were ISA, and 53 (1%) were located over side
      branches (SB). At 6 months, 3,905 struts were analyzed: 32 (1%) ISA, and 35 (1%)
      at the SB. Persistent ISA was observed more frequently than late acquired-ISA
      (81% vs. 16%, respectively; 3% were unmatchable). Late acquired ISA was
      associated with scaffold pattern irregularities, which were related to
      overstretching of the scaffold. Uncovered struts (63 struts, 2%) were more
      frequently observed in ISA and SB struts, compared with apposed struts (29% vs.
      1%; p < 0.01). Intraluminal masses (14 cross-sections, 3%; in 6 patients, 24%)
      were more frequently located at the site of ISA and/or uncovered struts (39% vs.
      2% and 13% vs. 2%, respectively; p < 0.01). CONCLUSIONS: The lack of strut
      apposition at baseline is related to the presence of uncovered struts and
      intraluminal masses at 6 month. An appropriate balloon/artery ratio respecting
      the actual vessel size and avoiding the overstretching of the scaffold can
      potentially decrease the risk of scaffold thrombosis. (ABSORB Clinical
      Investigation, Cohort B [ABSORB B).

PMID- 21939941
TI  - Percutaneous coronary revascularization for myocardial infarction in chronic
      kidney disease: recognizing the risk while seizing the benefits.

PMID- 21939940
TI  - Characteristics and in-hospital outcomes of patients with non-ST-segment
      elevation myocardial infarction and chronic kidney disease undergoing
      percutaneous coronary intervention.
AB  - OBJECTIVES: This study sought to evaluate the characteristics, therapies, and
      outcomes of patients with chronic kidney disease (CKD) presenting with non-ST
      segment elevation myocardial infarction (NSTEMI) and managed with percutaneous
      coronary intervention (PCI). This specific population has not been evaluated
      previously. BACKGROUND: Among patients with acute coronary syndrome, the presence
      of renal dysfunction is associated with an increased risk of death and major
      bleeding. METHODS: We examined data on 40,074 NSTEMI patients managed with PCI
      who were captured by the ACTION (Acute Coronary Treatment and Intervention
      Outcomes Network) registry. Patients were divided according to baseline renal
      function in 4 groups: no CKD and CKD stages 3, 4, and 5. RESULTS: Overall, 31.1%
      (n = 12,045) of patients with NSTEMI undergoing PCI had CKD. Compared with
      patients with normal renal function, CKD patients managed with PCI had
      significantly more history of myocardial infarction, heart failure, and more 3
      vessel coronary artery disease. They received fewer antithrombotic therapies but
      were treated more frequently with bivalirudin. In addition, they had
      significantly higher rates of in-hospital mortality and major bleeding. CKD stage
      4 was associated with the highest risk of adverse events relative to no CKD. The
      multivariable adjusted odds ratios of in-hospital mortality for CKD stages 3, 4,
      and 5 relative to no CKD were 2.0, 2.8, and 2.6, respectively (global p value
      <0.0001), and the analogous adjusted odds ratios of major bleeding were 1.5, 2.8,
      and 1.8, respectively (global p value <0.0001). CONCLUSIONS: CKD patients
      presenting with NSTEMI and managed with PCI have more comorbidities and receive
      guideline-recommended therapies less frequently than do patients without CKD. CKD
      is strongly associated with in-hospital mortality and bleeding in NSTEMI patients
      undergoing PCI.

PMID- 21939943
TI  - Surgical candidacy and selection biases in nonemergent left main stenting:
      implications for observational studies.
AB  - OBJECTIVES: This study sought to characterize reasons for surgical ineligibility
      in patients undergoing nonemergent unprotected left main (ULM) percutaneous
      coronary intervention (PCI) and to assess the potential for these reasons to
      confound comparative effectiveness studies of coronary revascularization.
      BACKGROUND: Although both PCI and coronary artery bypass graft surgery are
      treatments for ULM disease, some patients are not eligible for both treatments,
      which may result in treatment selection biases. METHODS: In 101 consecutive
      patients undergoing nonemergent ULM PCI, mixed methods were used to determine the
      prevalence of treatment selection dictated by surgical ineligibility and to
      identify the reasons cited for avoiding coronary artery bypass graft surgery. We
      then determined whether these reasons were captured by the ACC-NCDR (American
      College of Cardiology-National Cardiovascular Data Registry) Cath-PCI dataset to
      assess the ability of this registry to account for biases in treatment selection.
      Finally, the association of surgical eligibility with long-term outcomes after
      ULM PCI was assessed. RESULTS: Treatment selection was dictated by surgical
      ineligibility in over half the ULM PCI cohort with the majority having reasons
      for ineligibility not captured by the ACC-NCDR. Surgical ineligibility was a
      significant predictor of mortality after adjustment for Society of Thoracic
      Surgeons (hazard ratio [HR]: 5.4, 95% confidence interval [CI]: 1.2 to 25),
      EuroSCORE (European System for Cardiac Operative Risk Evaluation) (HR: 5.9, 95%
      CI: 1.3 to 27), or NCDR mortality scores (HR: 6.2, 95% CI: 1.4 to 27).
      CONCLUSIONS: Surgical ineligibility dictating treatment selection is common in
      patients undergoing nonemergent ULM PCI, occurs on the basis of risk factors not
      captured by the ACC-NCDR, and is independently associated with worse long-term
      outcomes after adjusting for standard risk scores.

PMID- 21939942
TI  - Long-term impact of chronic kidney disease in patients with ST-segment elevation
      myocardial infarction treated with primary percutaneous coronary intervention:
      the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute
      Myocardial Infarction) trial.
AB  - OBJECTIVES: This study sought to investigate the impact of chronic kidney disease
      (CKD) in patients undergoing percutaneous coronary intervention (PCI) for ST
      segment elevation myocardial infarction (STEMI) with different antithrombotic
      strategies. BACKGROUND: CKD is associated with increased risk of adverse ischemic
      and hemorrhagic events after primary PCI for STEMI. METHODS: HORIZONS-AMI
      (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial
      Infarction) trial was a multicenter, international, randomized trial comparing
      bivalirudin monotherapy or heparin plus a glycoprotein IIb/IIIa inhibitor (GPI)
      during primary PCI in STEMI. CKD, defined as creatinine clearance <60 ml/min, was
      present at baseline in 554 of 3,397 patients (16.3%). Patients were followed for
      3 years. Net adverse cardiac event (NACE) was defined as the composite of death,
      reinfarction, ischemia-driven target vessel revascularization (TVR), stroke or
      non-coronary artery bypass grafting (CABG)-related major bleeding. RESULTS:
      Patients with CKD compared with patients without had higher rates of NACE (41.4%
      vs. 23.8%, p < 0.0001), death (18.7% vs. 4.4%, p < 0.0001), and major bleeding
      (19.3% vs. 6.7%, p < 0.0001). Multivariable analysis identified baseline
      creatinine as an independent predictor of death at 3 years (hazard ratio: 1.51,
      95% confidence interval: 1.21 to 1.87, p < 0.001). Patients with CKD randomized
      to bivalirudin monotherapy versus heparin plus GPI had no significant difference
      in major bleeding (19.0% vs. 19.6%, p = 0.72) or death (19.0% vs. 18.4%, p =
      0.88) at 3 years. In patients with CKD, there was no difference in the rates of
      TVR in bare-metal stents (BMS) versus drug-eluting stents (DES) at 3 years (14.1%
      vs. 15.1%, p = 0.8). CONCLUSIONS: STEMI patients with CKD have significantly
      higher rates of death and major bleeding compared with those without CKD. In
      patients with CKD, there appears to be no benefit of bivalirudin compared with
      heparin + GPI, or DES versus BMS during primary PCI in improving clinical
      outcomes.

PMID- 21939944
TI  - The hazards of comparative effectiveness when we cannot effectively compare.

PMID- 21939945
TI  - Time to significant gradient reduction following septal balloon occlusion
      predicts the magnitude of final gradient response during alcohol septal ablation
      in patients with hypertrophic obstructive cardiomyopathy.
AB  - OBJECTIVES: The purpose of this study was to investigate whether a relationship
      exists between an acute reduction in resting left ventricular outflow tract
      (LVOT) gradient with balloon occlusion and the final invasive gradient response
      following alcohol septal ablation (ASA). BACKGROUND: ASA is an alternative
      therapy to myectomy surgery to reduce the basal septal thickness and decrease the
      resting and/or provocable LVOT gradient in patients with hypertrophic
      cardiomyopathy. Patients have a variable gradient response to occlusion of the
      septal perforator artery before ethanol infusion for ASA. METHODS: From November
      1998 to November 2008, 120 patients (mean age 60 years [range 16 to 87 years],
      50% women) with hypertrophic cardiomyopathy underwent ASA at our institution. The
      resting LVOT gradient (peak systolic left ventricle [LV] pressure - peak systolic
      aortic pressure) was measured continuously during the ASA procedure. The time to
      significant LVOT gradient decrease (defined as >50% decrease from baseline) was
      recorded following balloon occlusion of the dominant septal perforator coronary
      artery, which was found to perfuse the basal septum based on contrast
      echocardiographic studies. RESULTS: The mean baseline resting LVOT gradient was
      86 +/- 43 mm Hg, and it decreased to 17 +/- 11 mm Hg following ASA (-80.2%). The
      mean time to significant gradient reduction was 3.6 +/- 2 min (range 25 s to 11
      min). The time to significant LVOT gradient reduction strongly correlated with
      the final magnitude of gradient reduction following ASA (r = -0.81, p < 0.001).
      CONCLUSIONS: This study demonstrates a correlation between the time to
      significant LVOT gradient reduction following septal perforator balloon occlusion
      and the magnitude of final gradient response after ASA.

PMID- 21939946
TI  - Outcome prediction of septal ablation in patients with hypertrophic
      cardiomyopathy still a long way to go.

PMID- 21939947
TI  - Catheterization for Congenital Heart Disease Adjustment for Risk Method (CHARM).
AB  - OBJECTIVES: This study sought to develop a method to adjust for case mix
      complexity in catheterization for congenital heart disease to allow equitable
      comparisons of adverse event (AE) rates. BACKGROUND: The C3PO (Congenital Cardiac
      Catheterization Project on Outcomes) has been prospectively collecting data using
      a Web-based data entry tool on all catheterization cases at 8 pediatric
      institutions since 2007. METHODS: A multivariable logistic regression model with
      high-severity AE outcome was built using a random sample of 75% of cases in the
      multicenter cohort; the models were assessed in the remaining 25%. Model
      discrimination was assessed by the C-statistic and calibration with Hosmer
      Lemeshow test. The final models were used to calculate standardized AE ratios.
      RESULTS: Between August 2007 and December 2009, 9,362 cases were recorded at 8
      pediatric institutions of which high-severity events occurred in 454 cases (5%).
      Assessment of empirical data yielded 4 independent indicators of hemodynamic
      vulnerability. Final multivariable models included procedure type risk category
      (odds ratios [OR] for category: 2 = 2.4, 3 = 4.9, 4 = 7.6, all p < 0.001), number
      of hemodynamic indicators (OR for 1 indicator = 1.5, >=2 = 1.8, p = 0.005 and p <
      0.001), and age <1 year (OR: 1.3, p = 0.04), C-statistic 0.737, and Hosmer
      Lemeshow test p = 0.74. Models performed well in the validation dataset, C
      statistic 0.734. Institutional event rates ranged from 1.91% to 7.37% and
      standardized AE ratios ranged from 0.61 to 1.41. CONCLUSIONS: Using CHARM
      (Catheterization for Congenital Heart Disease Adjustment for Risk Method) to
      adjust for case mix complexity should allow comparisons of AE among institutions
      performing catheterization for congenital heart disease.

PMID- 21939948
TI  - Optical frequency domain imaging of stent fracture and coronary dissection
      associated with intraplaque hemorrhage.

PMID- 21939949
TI  - First valve-in-valve direct transaortic CoreValve implantation in an insufficient
      Sapien valve.

PMID- 21939950
TI  - Door-to-balloon time and ST-segment elevation myocardial infarction.

PMID- 21939952
TI  - Out-of-hospital cardiac arrest patients with ST-segment elevation on
      electrocardiogram: don't rush patients for emergent percutaneous coronary
      intervention in the era of aggressive door-to-balloon time.

PMID- 21939954
TI  - Ode to Walter Reed.

PMID- 21939955
TI  - Microinvasive adenocarcinoma of the cervix.
AB  - OBJECTIVE: We compared the outcomes of microinvasive squamous cell carcinoma and
      adenocarcinoma of the cervix and examined the safety of fertility-conserving
      treatment. STUDY DESIGN: The Surveillance, Epidemiology, and End Results database
      was used to identify all women with stage IA1 and IA2 cervical carcinoma
      diagnosed from 1988 to 2005. The treatment and outcomes of women with
      adenocarcinomas were compared with squamous cell carcinomas. RESULTS: A total of
      3987 women including 988 with adenocarcinomas (24.8%) were identified. Women with
      adenocarcinoma were more often white and were younger (P < .05 for all). Survival
      for stage IA1 adenocarcinomas (hazard ratio, 0.79; 95% confidence interval, 0.21
      2.94) was similar to that of women with squamous cell tumors. For stage IA2
      tumors, survival was similar for squamous cell and adenocarcinomas (hazard ratio,
      0.51; 95% confidence interval, 0.18-1.47). For stage IA1 and IA2 adenocarcinomas,
      survival was similar for conization and hysterectomy. CONCLUSION: Survival is
      similar for microinvasive adenocarcinomas and squamous cell carcinomas.
      Conization appears to be adequate treatment for microinvasive adenocarcinoma.

PMID- 21939956
TI  - Anesthetic management as a risk factor for postpartum hemorrhage after cesarean
      deliveries.
AB  - OBJECTIVE: This population-based study aimed to compare the risk of postpartum
      hemorrhage (PPH) for patients who underwent cesarean section delivery (CS) with
      general vs spinal/epidural anesthesia. STUDY DESIGN: We identified 67,328 women
      who had live singleton births by CS by linking the Taiwan National Health
      Insurance Research Dataset and the national birth certificate registry.
      Multivariate logistic regression was carried out to explore the relationship
      between anesthetic management type and PPH. RESULTS: Women who received general
      anesthesia had a higher rate of PPH than women who received epidural anesthesia
      (5.1% vs 0.4%). The odds of PPH in women who had CS with general anesthesia were
      8.15 times higher (95% confidence interval, 6.43-10.33) than for those who had CS
      with epidural anesthesia, after adjustment was made for the maternal and fetal
      characteristics. CONCLUSION: The odds that women will experience cesarean PPH
      with general anesthesia are approximately 8.15 times higher than for women who
      undergo CS with epidural anesthesia.

PMID- 21939957
TI  - Predictors of low cardiac output syndrome after isolated coronary artery bypass
      surgery: trends over 20 years.
AB  - BACKGROUND: Postoperative low cardiac output syndrome (LCOS) is associated with
      high morbidity and mortality after coronary artery bypass grafting (CABG). We
      sought to examine trends in predictors of LCOS after isolated CABG. METHODS: A
      total of 25,176 consecutive patients who underwent isolated CABG between 1990 and
      2009 were included. To examine trends over time, we divided patients into four
      equivalent eras (1990 to -1994, n = 6,489; 1995 to 1999, n = 8,175; 2000 to 2004,
      n = 6,741; 2005 to 2009, n = 3,797). We used multivariable analysis to identify
      predictors of LCOS. RESULTS: The prevalence of LCOS declined from 9.1% (1990 to
      1994) to 2.4% (2005 to 2009, p < 0.001). The following were the major independent
      predictors of LCOS for the entire cohort (odds ratios in parentheses):
      reoperative CABG (4.1); earlier year of operation (4.1, 2.6, 1.7 for the first,
      second, and third eras, respectively); left ventricular ejection fraction (LVEF)
      less than 0.20 (3.5), emergency surgery (2.7), cardiogenic shock (2.3), female
      gender (2), and LVEF 0.20 to 0.39 (2). Unlike other risk factors, the impact of
      LVEF less than 0.20 on development of postoperative LCOS increased substantially
      in the latest era (odds ratio, 7.8) compared with (odds ratios, 3.1, 4.3, and
      3.2) the first, second, and third eras, respectively. CONCLUSIONS: The impact of
      LVEF less than 0.20 on development of postoperative LCOS has increased markedly
      in the latest era of our study. Prudent preoperative evaluation in patients with
      severe left ventricular dysfunction is critical. Further innovative research in
      myocardial protection and circulatory support is warranted in patients with
      severe left ventricular dysfunction.

PMID- 21939958
TI  - Hybrid coronary revascularization versus off-pump coronary artery bypass grafting
      for the treatment of multivessel coronary artery disease.
AB  - BACKGROUND: Hybrid coronary revascularization (HCR) combines a minimally invasive
      (3-cm anterolateral thoracotomy), sternal-sparing, off-pump left internal mammary
      artery-left anterior descending (LIMA-LAD) coronary artery anastomosis with
      percutaneous coronary intervention (PCI) to non-LAD coronary arteries. We
      compared outcomes of HCR versus traditional off-pump coronary artery bypass
      grafting (OPCAB) for the treatment of multivessel coronary artery disease (CAD).
      METHODS: Between October 8, 2003 and April 23, 2010, 147 patients with
      multivessel coronary disease were treated with HCR at a US academic center. These
      were matched 4:1 to 588 contemporaneous patients treated with multivessel OPCAB
      by sternotomy using an optimal matching algorithm with 8 preoperative variables:
      age, gender, ejection fraction, presence of diabetes, myocardial infarction (MI),
      number of diseased vessels, left main coronary artery disease, and Society of
      Thoracic Surgeons (STS) predicted risk of mortality (PROM) score. In-hospital
      major adverse events (MACCE) and the need for repeated revascularization during
      follow-up were compared between groups. All-cause mortality was determined using
      the Social Security Death Index (SSDI). RESULTS: Matching produced groups with
      similar coronary anatomy and statistically similar preoperative risk factors. The
      incidence of MACCE was similar between groups (3/147 HCR versus 12/588 OPCAB).
      During a median 3.2 years of follow up, the need for repeated revascularization
      was higher for HCR than for OPCAB (18/147 [12.2%] versus 22/588 [3.7%]; p <
      0.001). The incidence of blood transfusion was higher for the OPCAB group.
      Estimated 5-year survival was similar between groups (OPCAB, 84.3% versus HCR,
      86.8%; p = 0.61). CONCLUSIONS: Hybrid coronary revascularization is a minimally
      invasive treatment for multivessel CAD. Although repeated revascularization was
      greater with HCR, both in-hospital and midterm outcomes were comparable with
      those of traditional OPCAB. Further investigation into the comparative
      effectiveness of this alternative strategy is warranted.

PMID- 21939959
TI  - Deterioration of mitral valve competence after the repair of atrial septal defect
      in adults.
AB  - BACKGROUND: Although mild mitral regurgitation (MR) associated with atrial septal
      defect (ASD) is believed to improve by ASD closure alone, new-onset MR or
      aggravation of preexisting mild MR may also develop after ASD closure. We sought
      to determine the preoperative risk factors for the postoperative deterioration of
      mitral valve competence in adults with ASD. METHODS: Retrospective review of 286
      adults with ASD who had undergone surgical closure of ASD between January 2004
      and December 2009 was performed. Patients with significant preoperative MR
      (>=III/IV) that necessitated mitral valve intervention were excluded.
      Preoperative MR grades were 0 in 204 patients, I in 67 patients, and II in 15
      patients. RESULTS: After ASD repair, MR degree did not change or improved in most
      of the patients (204 of 286, 71%), whereas 82 patients (82 of 286, 29%) showed
      aggravated or new-onset MR, including 18 patients whose MR degree increased by
      grade 2 or more. Univariable analysis revealed older age, preoperative atrial
      fibrillation, large left atrial size, large indexed ASD size, high peak tricuspid
      regurgitation velocity, and associated tricuspid valve surgery or Maze procedure
      as risk factors for new-onset or aggravated MR, but only older age (odds ratio,
      1.058; 95% confidence interval, 1.025 to 1.092; p = 0.0005) and indexed ASD size
      (odds ratio, 1.120; 95% confidence interval, 1.042 to 1.205; p = 0.0022) remained
      significant on multivariable analysis. The ratio of postoperative left
      ventricular end-diastolic volume to preoperative left ventricular end-diastolic
      volume was greater in patients with new-onset or aggravated MR (p = 0.016).
      CONCLUSIONS: Mitral valve competence may deteriorate after ASD closure in older
      patients with large ASD.

PMID- 21939960
TI  - Treatment manuals: use in the treatment of bulimia nervosa.
AB  - As psychology has moved toward emphasizing evidence-based practice, use of
      treatment manuals has extended from research trials into clinical practice.
      Minimal research has directly evaluated use of manuals in clinical practice. This
      survey of international eating disorder professionals examined use of manuals
      with 259 clinicians' most recent client with bulimia nervosa. Although evidence
      based manuals for bulimia nervosa exist, only 35.9% of clinicians reported using
      a manual. Clinicians were more likely to use a manual if they were younger; were
      treating an adult client; were clinical psychologists; were involved in research
      related to eating disorders; and endorsed a cognitive-behavioral orientation.
      Clinicians were less likely to use a manual if they provided eclectic
      psychotherapy that incorporated multiple psychotherapeutic approaches. We
      conclude that psychotherapy provided in clinical practice often does not align
      with the specific form validated in research trials, and "eclecticism" is at odds
      with efforts to disseminate manuals into clinical practice.

PMID- 21939961
TI  - Identification of novel mimicry epitopes for cardiac myosin heavy chain-alpha
      that induce autoimmune myocarditis in A/J mice.
AB  - Myocarditis is one cause of sudden cardiac death in young adolescents, and
      individuals affected with myocarditis can develop dilated cardiomyopathy, a
      frequent reason for heart transplantation. Exposure to environmental microbes has
      been suspected in the initiation of heart autoimmunity, but the direct causal
      link is lacking. We report here identification of novel mimicry epitopes that
      bear sequences similar to those in cardiac myosin heavy chain (MYHC)-alpha 334
      352. These epitopes represent Bacillus spp., Magnetospirillum gryphiswaldense,
      Cryptococcus neoformans and Zea mays. The mimicry peptides induced varying
      degrees of myocarditis in A/J mice reminiscent of the disease induced with MYHC
      alpha 334-352. We demonstrate that the mimics induce cross-reactive T cell
      responses for MYHC-alpha 334-352 as verified by MHC class II IA(k)/tetramer
      staining and Th-1 and Th-17 cytokines similar to those of MYHC-alpha 334-352. The
      data suggest that exposure to environmental microbes which are otherwise
      innocuous can predispose to heart autoimmunity by molecular mimicry.

PMID- 21939962
TI  - A five-colour colour-coded mapping method for DCE-MRI analysis of head and neck
      tumours.
AB  - AIM: To devise a method to convert the time-intensity curves (TICs) of head and
      neck dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) data into a
      pixel-by-pixel colour-coded map for identifying normal tissues and tumours.
      MATERIALS AND METHODS: Twenty-three patients with head and neck squamous cell
      carcinoma (HNSCC) underwent DCE-MRI. TIC patterns of primary tumours, metastatic
      nodes, and normal tissues were assessed and a program was devised to convert the
      patterns into a classified colour-coded map. The enhancement patterns of tumours
      and normal tissue structures were evaluated and categorized into nine grades (0
      8) based on the predominance of coloured pixels on maps. RESULTS: Five identified
      TIC patterns were converted into a colour-coded map consisting of red (maximum
      enhancement), brown (continuous slow rise-up), yellow (rapid wash-in and wash
      out), green (rapid wash-in and plateau), and blue (rapid wash-in and rise-up).
      The colour-coded map distinguished all 21 primary tumours and 15 metastatic nodes
      from normal structures. Primary tumours and metastatic nodes were colour coded as
      predominantly yellow (grades 1-2) in 17/21 and 6/15, green (grades 3-5) in 3/21
      and 5/15, and blue (grades 6-7) in 1/21 and 4/15, respectively. Vessels were
      coded red in 46/46 (grade 0) and muscles were coded brown in 23/23 (grade 8).
      Salivary glands, thyroid glands, and palatine tonsils were coded into
      predominantly yellow (grade 1) in 46/46 and 10/10 and 18/22, respectively.
      CONCLUSION: DCE-MRI derived five-colour-coded mapping provides an objective easy
      to-interpret method to assess the dynamic enhancement pattern of head and neck
      cancers.

PMID- 21939963
TI  - SAPHO: What radiologists should know.
AB  - SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) is an umbrella
      acronym for inflammatory clinical conditions whose common denominator is aseptic
      osteoarticular involvement with characteristic skin lesions. It involves all
      ages, can involve any skeletal site, and has variable imaging appearances
      depending on the stage/age of the lesion and imaging method. It mimics important
      differentials including infection and neoplasia. Awareness of the imaging
      features, especially in the spine, facilitates early diagnosis, prevents repeated
      biopsies, and avoids unnecessary surgery, while initiating appropriate treatment.

PMID- 21939964
TI  - Digital tomosynthesis of the chest: utility for detection of lung metastasis in
      patients with colorectal cancer.
AB  - AIM: To evaluate the performance of digital tomosynthesis (DT) of the chest for
      detection of lung nodules in patients with colorectal cancer (CRC). MATERIALS AND
      METHODS: The institutional review board approved this study, and all patients
      provided informed consent. A commercial caesium iodide/amorphous silicon (CsI/a
      Si) flat-panel detector system was used to verify the performance of the DT and
      chest radiography (XR) methods. DT was performed in 142 patients with CRC. All
      142 patients underwent chest computed tomography (CT) within a week of DT. As a
      reference standard, two radiologists reviewed the chest CT in consensus and
      recorded the presence of pulmonary nodules. Another two radiologists
      independently observed the DT images and recorded the presence of pulmonary
      nodules. The status of all lung nodules was assessed either histologically or by
      follow-up over a period of 1 year. The nodules were classified into metastasis,
      benign, and uncertain. Statistical analysis of the results was performed.
      RESULTS: Two hundred and thirty-seven nodules from 142 patients were found at CT.
      These included 71 proven metastases and 126 benign nodules; 40 nodules were
      uncertain. Observers detected 83% of all lung nodules and 93% of proven
      metastases using DT. Among 237 nodules, 147 nodules were larger than 4mm in
      diameter on the CT images. Observers detected 87% of lung nodules that were
      larger than 4mm. CONCLUSION: Despite a reasonably low radiation dose, DT is a
      sensitive method, and is comparable to chest CT for the detection of lung
      nodules, particularly metastatic lung nodules in patients with CRC.

PMID- 21939966
TI  - The mental representation of integers: an abstract-to-concrete shift in the
      understanding of mathematical concepts.
AB  - Mathematics has a level of structure that transcends untutored intuition. What is
      the cognitive representation of abstract mathematical concepts that makes them
      meaningful? We consider this question in the context of the integers, which
      extend the natural numbers with zero and negative numbers. Participants made
      greater and lesser judgments of pairs of integers. Experiment 1 demonstrated an
      inverse distance effect: When comparing numbers across the zero boundary, people
      are faster when the numbers are near together (e.g., -1 vs. 2) than when they are
      far apart (e.g., -1 vs. 7). This result conflicts with a straightforward symbolic
      or analog magnitude representation of integers. We therefore propose an analog-x
      hypothesis: Mastering a new symbol system restructures the existing magnitude
      representation to encode its unique properties. We instantiate analog-x in a
      reflection model: The mental negative number line is a reflection of the positive
      number line. Experiment 2 replicated the inverse distance effect and corroborated
      the model. Experiment 3 confirmed a developmental prediction: Children, who have
      yet to restructure their magnitude representation to include negative magnitudes,
      use rules to compare negative numbers. Taken together, the experiments suggest an
      abstract-to-concrete shift: Symbolic manipulation can transform an existing
      magnitude representation so that it incorporates additional perceptual-motor
      structure, in this case symmetry about a boundary. We conclude with a second
      symbolic-magnitude model that instantiates analog-x using a feature-based
      representation, and that begins to explain the restructuring process.

PMID- 21939965
TI  - Perceptual learning evidence for contextually-specific representations.
AB  - Listeners rapidly adjust to talkers' pronunciations, accommodating those
      pronunciations into the relevant phonemic category to improve subsequent
      perception. Previous work has suggested that such learning is restricted to
      pronunciations that are representative of how the speaker talks (Kraljic, Samuel,
      & Brennan, 2008). If an ambiguous pronunciation, for example, can be attributed
      to an external source (such as a pen in the speaker's mouth), or if it is
      preceded by normal pronunciations of the same sound, learning is blocked. In
      three experiments, we explore this blocking effect in more detail. Our aim is to
      better understand the nature of the representations underlying the perceptual
      learning process. Experiment 1 replicates the blocking effect. Experiments 2 and
      3 demonstrate that it can be eliminated when certain visual information occurs
      simultaneously with the auditory signal. The pattern of learning and non-learning
      is best accounted for by the view that speech perception is mediated by episodic
      representations that include potentially relevant visual information.

PMID- 21939967
TI  - Preschoolers' interpretations of gesture: label or action associate?
AB  - This study explores a common assumption made in the cognitive development
      literature that children will treat gestures as labels for objects. Without
      doubt, researchers in these experiments intend to use gestures symbolically as
      labels. The present studies examine whether children interpret these gestures as
      labels. In Study 1 two-, three-, and four-year olds tested in a training paradigm
      learned gesture-object pairs for both iconic and arbitrary gestures. Iconic
      gestures became more accurate with age, while arbitrary gestures did not. Study 2
      tested the willingness of children aged 40-60 months to fast map novel nouns,
      iconic gestures and arbitrary gestures to novel objects. Children used fast
      mapping to choose objects for novel nouns, but treated gesture as an action
      associate, looking for an object that could perform the action depicted by the
      gesture. They were successful with iconic gestures but chose objects randomly for
      arbitrary gestures and did not fast map. Study 3 tested whether this effect was a
      result of the framing of the request and found that results did not change
      regardless of whether the request was framed with a deictic phrase ("this one
      <gesture>") or an article ("a <gesture>"). Implications for preschool children's
      understanding of iconicity, and for their default interpretations of gesture are
      discussed.

PMID- 21939968
TI  - Effect of CPAP therapy on daytime cardiovascular regulations in patients with
      obstructive sleep apnea.
AB  - Obstructive sleep apnea (OSA) is a sleep disorder with a high prevalence that
      causes pathological changes in cardiovascular regulation during the night and
      also during daytime. We investigated whether the treatment of OSA at night by
      means of continuous positive airway pressure (CPAP) improves the daytime
      consequences. Twenty-eight patients with OSA, 18 with arterial hypertension, 10
      with normal blood pressure, were investigated at baseline and with three months
      of CPAP treatment. Ten age and sex matched healthy control subjects were
      investigated for comparisons. We recorded a resting period with 20min quiet
      breathing and an exercise stress test during daytime with ECG and blood pressure
      (Portapres). The bicycle ergometry showed a significant reduction of the
      diastolic blood pressure at a work load of 50W and 100W (p<0.05 and p<0.01,
      respectively) and a decrease of the heart rate recovery time after the stress
      test (p<0.05). These results indicate a reduction of vascular resistance and
      sympathetic activity during daytime. The coupling analysis of the resting periods
      by means of symbolic coupling traces approach indicated an effect of the CPAP
      therapy on the baroreflex reaction in hypertensive patients where influences of
      the systolic blood pressure on the heart rate changed from pathological patterns
      to adaptive mechanisms of the normotensive patients (p<0.05).

PMID- 21939969
TI  - Abdominal trauma in pregnancy.

PMID- 21939970
TI  - Redefining hypotension in traumatic brain injury.
AB  - BACKGROUND: Systemic hypotension is a well documented predictor of increased
      mortality following traumatic brain injury (TBI). Hypotension is traditionally
      defined as systolic blood pressure (SBP)<90 mmHg. Recent evidence defines
      hypotension by a higher SBP in injured (non-TBI) trauma patients. We hypothesize
      that hypotension threshold requires a higher SBP in isolated moderate to severe
      TBI. PATIENTS AND METHODS: A retrospective database review of all adults (>= 15
      years) with isolated moderate to severe TBI (head abbreviated injury score
      (AIS)>= 3, all other AIS <= 3), admitted from five Level I and eight Level II
      trauma centres (Los Angeles County), between 1998 and 2005. Several fit statistic
      analyses were performed for each admission SBP from 60 to 180 mmHg to identify
      the model that most accurately defined hypotension for three age groups: 15-49
      years, 50-69 years, and >= 70 years. The main outcome variable was mortality, and
      the optimal definition of hypotension for each group was determined from the best
      fit model. Adjusted odds ratios (AOR) were then calculated to determine increased
      odds in mortality for the defined optimal SBP within each age group. RESULTS: A
      total of 15,733 patients were analysed. The optimal threshold of hypotension
      according to the best fit model was SBP of 110 mmHg for patients 15-49 years (AOR
      1.98, CI 1.65-2.39, p<0.0001), 100 mmHg for patients 50-69 years (AOR 2.20, CI
      1.46-3.31, p=0.0002), and 110 mmHg for patients >= 70 years (AOR 1.92, CI 1.35
      2.74, p=0.0003). CONCLUSIONS: Patients with isolated moderate to severe TBI
      should be considered hypotensive for SBP<110 mmHg. Further research should
      confirm this new definition of hypotension by correlation with indices of
      perfusion.

PMID- 21939971
TI  - Paediatric trauma mortality in Norway: a population-based study of injury
      characteristics and urban-rural differences.
AB  - INTRODUCTION: Paediatric injury is a major global public health challenge.
      Epidemiological research is required for effective primary injury prevention and
      to develop trauma systems for optimal management of childhood injuries. This
      study aimed to describe the characteristics and geographical distribution of
      paediatric trauma deaths and to assess the relationship between rural locations
      and mortality rates. MATERIALS AND METHODS: By accessing national registries, all
      trauma related deaths of persons aged 0-15 years in Norway from 1998 to 2007 were
      included. Paediatric trauma mortality rates and injury characteristic were
      analysed in relation to three different measures of municipal rurality:
      centrality, population density and settlement density. RESULTS: There were 462
      trauma related deaths during the study period and the national annual paediatric
      mortality rate was 4.81/100000. Rural areas had higher mortality rates, and this
      difference was best predicted by municipal centrality. Rural trauma was
      characterised by traffic accidents and deaths that occurred prior to reaching
      hospital. The rural and northernmost county, Finnmark, had a mortality rate three
      times the national average. CONCLUSION: Mortality rates after childhood injury
      are high in rural areas. Substantiated measures of rurality are required for
      optimal allocation of primary and secondary preventive measures.

PMID- 21939972
TI  - Continuous lateral rotational therapy and systemic inflammatory response in
      posttraumatic acute lung injury: results from a prospective randomised study.
AB  - BACKGROUND: The incidence of posttraumatic acute lung injury is high and may
      result in increased mortality. Changes in the body position are additional
      measures to improve pulmonary gas exchange and to prevent pulmonary
      complications. We investigated the effect of a continuous lateral rotational
      therapy (CLRT) on the inflammatory response in patients with posttraumatic lung
      failure. METHODS: After admission to the intensive care unit (ICU) and after
      randomisation, 13 patients were placed in a special motor-driven bed and CLRT was
      performed for 5 days. In the control group (n=14), patients were positioned
      conventionally. Samples from blood and from broncho-alveolar lavage fluid (BAL)
      were collected in both groups before study began and on day 5. The levels of
      cytokines (Tumour Necrosis Factor, Interleukin 6, Interleukin 8 or Intercellular
      Adhesion Molecule-1) were assessed and haemodynamic, pulmonary, and laboratory
      values were documented. RESULTS: On day 5, no significant differences were found
      in cytokine levels between groups, but a significant decrease in IL-8 (p<0.01)
      and TNF-alpha (p<0.05) serum levels and an increase in IL-8 BAL levels was found
      in the CLRT-group, but not for conventionally managed patients. In general
      cytokine BAL levels tended to be increased in both groups, but more pronounced
      during CLRT. Daily assessment of the severity of disease (SAPS-II, SOFA) was
      significantly reduced in the study group on days 2-4 (p<0.05) in comparison to
      control group. CONCLUSIONS: CLRT may attenuate the inflammatory response to
      posttraumatic acute lung injury. The exact mechanism of such an effect is
      unknown.

PMID- 21939973
TI  - Tranexamic acid for postpartum bleeding.

PMID- 21939974
TI  - Primary urothelial cell carcinoma of the vagina.

PMID- 21939975
TI  - Patient and provider attitudes toward screening for Down syndrome in a Latin
      American country where abortion is illegal.
AB  - OBJECTIVE: To examine patient and provider attitudes toward first trimester
      nuchal translucency (NT) screening for Down syndrome and to assess how patients
      consent to screening in a country where abortion is illegal. METHODS: Patients
      presenting for first trimester ultrasound including NT screening in two obstetric
      units in Chile completed a questionnaire about their attitudes toward NT
      screening and perspectives on the consent process. A follow-up questionnaire
      assessed satisfaction with the test. Prenatal care providers also completed a
      questionnaire ascertaining their perspectives on NT screening. RESULTS: A total
      of 107 patients completed the initial questionnaire and 78 completed the follow
      up questionnaire. Although 98 (94%) patients desired NT screening only 38 (38%)
      indicated that they would undergo diagnostic testing if they received screen
      positive results. Only 3 patients screened positive; however, 15 (20%)
      participants experienced increased anxiety after the test. Almost all of the 36
      providers surveyed indicated that they counsel their patients thoroughly, but 38
      (39%) patients reported that they received adequate information. CONCLUSION: NT
      screening is often performed without patients' full understanding of the
      implications of potential results and may cause anxiety. Providers should elicit
      patients' preferences regarding prenatal testing and engage them in shared
      decision making about whether to undergo screening, particularly when abortion is
      not an option.

PMID- 21939976
TI  - The use of ammonium hydroxide as an additive in supercritical fluid
      chromatography for achiral and chiral separations and purifications of small,
      basic medicinal molecules.
AB  - This study describes using 0.1% of a 28-30% ammonium hydroxide solution as an
      additive to alcohol modifiers in SFC to improve chromatographic peak shapes for
      basic molecules. Ammonium hydroxide's high volatility leaves no residual additive
      in the purified sample unlike classical additives in preparative chromatography
      such as diethylamine and triethylamine. We demonstrate that the silica support is
      stable despite having ammonium hydroxide in the modifier by running a durability
      study for over 350 h (105 L of solvent, 105,000 column volumes) on an analytical
      Chiralcel OJ column and a second study for 30 h (7.2 L, 14,400 column volumes) on
      an analytical Lux Cellulose-1 column. The peak shape of small, basic molecules is
      greatly improved with the use of ammonium hydroxide and this improvement is very
      similar to those having 0.1% diethylamine as a mobile phase additive.
      Electrospray ionization is also enhanced with the presence of ammonium hydroxide
      compared with that of diethylamine. We have found that the age of the 28-30%
      bottle of ammonium hydroxide solution can have significant effects on the
      chromatography and we describe how this can be overcome. Finally, we analyzed 23
      racemic and basic compounds on six different chiral stationary phases and found
      there to be very little chiral selectivity difference between ammonium hydroxide
      and diethylamine, triethylamine, ethanolamine and isopropylamine.

PMID- 21939977
TI  - Size exclusion chromatography-gradients, an alternative approach to polymer
      gradient chromatography: 2. Separation of poly(meth)acrylates using a size
      exclusion chromatography-solvent/non-solvent gradient.
AB  - A gradient ranging from methanol to tetrahydrofuran (THF) was applied to a series
      of poly(methyl methacrylate) (PMMA) standards, using the recently developed
      concept of SEC-gradients. Contrasting to conventional gradients the samples
      eluted before the solvent, i.e. within the elution range typical for separations
      by SEC, however, the high molar mass PMMAs were retarded as compared to
      experiments on the same column using pure THF as the eluent. The molar mass
      dependence on retention volume showed a complex behaviour with a nearly molar
      mass independent elution for high molar masses. This molar mass dependence was
      explained in terms of solubility and size exclusion effects. The solubility based
      SEC-gradient was proven to be useful to separate PMMA and poly(n-butyl crylate)
      (PnBuA) from a poly(t-butyl crylate) (PtBuA) sample. These samples could be
      separated neither by SEC in THF, due to their very similar hydrodynamic volumes,
      nor by an SEC-gradient at adsorbing conditions, due to a too low selectivity. The
      example shows that SEC-gradients can be applied not only in adsorption/desorption
      mode, but also in precipitation/dissolution mode without risking blocking
      capillaries or breakthrough peaks. Thus, the new approach is a valuable
      alternative to conventional gradient chromatography.

PMID- 21939978
TI  - Computation of distribution of minimum resolution for log-normal distribution of
      chromatographic peak heights.
AB  - General equations are derived for the distribution of minimum resolution between
      two chromatographic peaks, when peak heights in a multi-component chromatogram
      follow a continuous statistical distribution. The derivation draws on published
      theory by relating the area under the distribution of minimum resolution to the
      area under the distribution of the ratio of peak heights, which in turn is
      derived from the peak-height distribution. Two procedures are proposed for the
      equations' numerical solution. The procedures are applied to the log-normal
      distribution, which recently was reported to describe the distribution of
      component concentrations in three complex natural mixtures. For published
      statistical parameters of these mixtures, the distribution of minimum resolution
      is similar to that for the commonly assumed exponential distribution of peak
      heights used in statistical-overlap theory. However, these two distributions of
      minimum resolution can differ markedly, depending on the scale parameter of the
      log-normal distribution. Theory for the computation of the distribution of
      minimum resolution is extended to other cases of interest. With the log-normal
      distribution of peak heights as an example, the distribution of minimum
      resolution is computed when small peaks are lost due to noise or detection
      limits, and when the height of at least one peak is less than an upper limit. The
      distribution of minimum resolution shifts slightly to lower resolution values in
      the first case and to markedly larger resolution values in the second one. The
      theory and numerical procedure are confirmed by Monte Carlo simulation.

PMID- 21939979
TI  - 1.1 MUm superficially porous particles for liquid chromatography. Part I:
      synthesis and particle structure characterization.
AB  - Superficially porous particles are characterized by a non-porous particle core
      surrounded by a thin porous layer. Superficially porous particles have been shown
      to have chromatographic advantages over traditional totally porous particles by
      reducing the resistance to mass transfer and the eddy diffusion contributions to
      the theoretical plate height, particularly for biomolecule separations.
      Currently, 1.7 MUm superficially porous particles are commercially available, but
      a further decrease in the particle diameter and reduction in the porous layer
      thickness has the potential to further improve the efficiency of the column
      packing material. In this study, the synthesis of smaller diameter superficially
      porous particles was investigated. As the particle diameter was decreased,
      however, synthesis parameters previously reported were rendered unsuitable due to
      particle agglomeration, non-uniform coating, and porous layer disintegration.
      Parameters such as colloidal silica size, drying process, and sintering
      temperature were investigated to improve the structural characteristics of
      smaller diameter superficially porous particles. Reported is a synthetic route
      for production of 1.1 MUm superficially porous particles having a 0.1 MUm porous
      layer. Based on the revised method, the particles produced have a surface area,
      pore diameter, and particle size distribution RSD of 52 m(2)/g, 71 A, and 2.2%,
      respectively.

PMID- 21939980
TI  - Wettability of carbon nanofiber layers on nickel foils.
AB  - Carbon nanofiber (CNF) layers have been directly synthesized on nickel foils by
      chemical vapor deposition at 450 degrees C using different H(2) concentrations
      and reaction times. The addition of 5% H(2) produces thicker, rougher and more
      porous CNF layers than when 1% H(2) is used. The roughness and porosity increases
      with reaction time when 5%, 10% or 20% H(2) are used; however, this effect is
      less pronounced when 1% H(2) is used. CNFs are 50-55 nm in diameter and have a
      fishbone type structure. We have studied the influence of CNF layer thickness,
      porosity and surface roughness on the interaction with water by measuring the
      contact angle. The water wetting properties of the samples are more significantly
      influenced by the CNF layer thickness than both surface roughness and porosity.
      When the CNF layer is thicker than ca. 20 MUm, the surface is hydrophobic and the
      contact angle increases with surface roughness and porosity. When the CNF layer
      is thinner than ca. 20 MUm, the surface is hydrophilic and the contact angle
      decreases with increasing surface roughness and porosity. This behavior is
      attributed to penetration of water, making contact with the hydrophilic C layer
      between the CNF layer and the foil.

PMID- 21939981
TI  - Studies on the reaction pathway of arsenate adsorption at water-TiO2 interfaces
      using density functional theory.
AB  - Reaction pathway information of transition states and intermediate species is
      crucial for understanding the adsorption mechanism of pollutants at mineral-water
      interfaces. However, it has been difficult to obtain such information using
      existing experiments. Here, the activation barriers, transition states,
      intermediate species and surface complexes of arsenate adsorption on TiO(2)
      surfaces were studied using DFT-based reaction pathway calculations. The results
      indicated that the bidentate binuclear (BB) adsorption structure was formed
      through a monodentate mononuclear (MM) metastable-equilibrium adsorption (MEA)
      state. A two-step adsorption mechanism was proposed on the basis of the detailed
      picture of bond breaking and bond formation during each reaction step. When the
      adjacent surface sites were occupied, the transform from MM mode to BB mode was
      greatly inhibited so that both MM and BB coexisted in the equilibrium adsorption
      sample. The BB complex was energetically more stable than the MM complex, and so,
      the adsorption irreversibility was fundamentally related to the ratio BB:MM in
      the final equilibrium state. This mechanism may also explain the initial
      concentration effect, where, for the given adsorption experiment of arsenate on
      TiO(2) under the same thermodynamic conditions, both equilibrium constants and
      the BB:MM ratio in equilibrium adsorption samples changed with the reaction
      kinetics.

PMID- 21939982
TI  - The Gibbs-Duhem type relation for ionic/nonionic mixed micelles--an alternative
      approach to Hall's method.
AB  - The micellar Gibbs-Duhem relation for two-component ionic/nonionic mixed micelles
      is presented in terms of the apparent bound amount to micelles. For simplicity,
      the ionic surfactant and a salt are both uni-uni valent electrolytes and have a
      common counterion species. Compared to the theory by D.G. Hall on the basis of a
      consideration on the Donnan equilibrium [D.G. Hall, J. Chem. Soc. Faraday Trans.
      87 (1991) 3529], the present approach is simple and unambiguous. Considering
      changes at constant temperature and pressure, the two approaches provide nearly
      identical results.

PMID- 21939983
TI  - Sad or fearful? The influence of body posture on adults' and children's
      perception of facial displays of emotion.
AB  - The current research investigated the influence of body posture on adults' and
      children's perception of facial displays of emotion. In each of two experiments,
      participants categorized facial expressions that were presented on a body posture
      that was congruent (e.g., a sad face on a body posing sadness) or incongruent
      (e.g., a sad face on a body posing fear). Adults and 8-year-olds made more errors
      and had longer reaction times on incongruent trials than on congruent trials when
      judging sad versus fearful facial expressions, an effect that was larger in 8
      year-olds. The congruency effect was reduced when faces and bodies were
      misaligned, providing some evidence for holistic processing. Neither adults nor 8
      year-olds were affected by congruency when judging sad versus happy expressions.
      Evidence that congruency effects vary with age and with similarity of emotional
      expressions is consistent with dimensional theories and "emotional seed" models
      of emotion perception.

PMID- 21939984
TI  - A review of the health consequences of the vitamin D deficiency pandemic.
AB  - Rickets, osteomalacia, osteoporosis and myopathy are among the better known
      consequences of a low to very low vitamin D status. Over the past several years
      various predominantly epidemiological and prospective cohort studies have found
      associations between low vitamin D levels and various extraskeletal conditions.
      These findings may particularly become important over the next years since large
      proportions of the population have low vitamin D levels. Increasing incidence
      rates of obesity, adverse life-style factors and active avoidance of sunlight
      seem to decrease average population mean vitamin D levels further. This article
      gives a brief overview of known and also less well-established potential
      detrimental effects of a low vitamin D status.

PMID- 21939985
TI  - Bioaccumulation of metals by Fucus ceranoides in estuaries of South West England.
AB  - Fucus ceranoides tolerates abiotic conditions encountered across the full range
      of estuarine salinities. We examined the bioaccumulation of metals in individuals
      and metal concentrations in accompanying sediment samples collected at different
      locations along estuaries of South West England. Intra- and inter-estuarine
      variations in metal accumulation by F. ceranoides, after correction for
      particulate contamination using Fe as a proxy, were attributed to variations in
      the availabilities and concentrations of aqueous metals. Greatest accumulation
      was observed in estuaries that remain most heavily impacted by historical mining
      activities and for metals that were mobilised to the greatest extent during these
      operations (As, Cu, Sn, Zn). Arsenic concentrations displayed a seaward increase
      in estuaries in which multiple samples were taken, whereas Cd concentrations were
      always greatest in samples collected from the most landward locations. Ongoing
      research aims to better understand the mechanisms and kinetics of metal
      interactions with F. ceranoides and their dependence on salinity.

PMID- 21939986
TI  - At-sea detection of marine debris: overview of technologies, processes, issues,
      and options.
AB  - At-sea detection of marine debris presents a difficult problem, as the debris
      items are often relatively small and partially submerged. However, they may
      accumulate in water parcel boundaries or eddy lines. The application of models,
      satellite radar and multispectral data, and airborne remote sensing (particularly
      radar) to focus the search on eddies and convergence zones in the open ocean
      appear to be a productive avenue of investigation. A multistage modeling and
      remote sensing approach is proposed for the identification of areas of the open
      ocean where debris items are more likely to congregate. A path forward may best
      be achieved through the refinement of the Ghost Net procedures with the addition
      of a final search stage using airborne radar from an UAS simulator aircraft to
      detect zones of potential accumulation for direct search. Sampling strategies,
      direct versus indirect measurements, remote sensing resolution, sensor/platform
      considerations, and future state are addressed.

PMID- 21939987
TI  - [Factors related with the presence of erectile dysfunction in patients with
      obstructive sleep apnea].
AB  - BACKGROUND AND OBJECTIVE: Obstructive sleep apnea (OSA) syndrome can contribute
      to the development of erectile dysfunction (ED) through multiple mechanisms. The
      aim was to identify factors influencing the presence of ED in these patients.
      PATIENTS AND METHODS: Cross sectional study in men diagnosed with OSA by
      polysomnography. We obtained information about demographic variables, apnea
      hypopnea index (AHI), comorbidity, blood pressure, drugs, Epworth Sleepiness
      Scale, physical examination, electrocardiogram, ankle-brachial index and blood
      and urine analysis. The presence of ED was assessed by questionnaire IIEF-5.
      RESULTS: We included 142 patients, mean age was 53 (11) years. The prevalence of
      ED was 69%. We found significant differences in AHI between patients with mild
      and severe ED (41 [21] vs 63 [18], P=.023). ED was associated with hypertension
      (odds ratio [OR]=3.56 [1.64-7.72]), hypercholesterolemia (OR=7.19 [2.39-21.68]),
      diabetes mellitus type 2 (OR=3.07 [1.02-9.48]) and ischemic heart disease
      (OR=1.51 [1.33-1.70]); and treatment with antihypertensive (OR=4.05 [1.76-9.31)],
      lipid-lowering drugs (OR=9.71 [2.2-22.72]), anti-diabetic drugs (OR=3.21 [0.69
      14.89]), antiplatelet and anticoagulant agents (OR=6.44 [1.45-28.64]). After
      logistic regression analysis, only age (OR=1.11 [1.05-1.16]) and
      hypercholesterolemia (OR=4.87 [1.49-15.96]) were associated with ED. CONCLUSIONS:
      Patients with OSA have a high prevalence of ED, mainly in severe OSA. Factors
      influencing the presence of ED in patients with OSA are primarily age and
      hypercholesterolemia. Other factors that may be related include hypertension,
      poor metabolic control, ischemic heart disease, and treatment with
      antihypertensive, lipid-lowering and anti-diabetic drugs.

PMID- 21939988
TI  - [Rhabdomyolysis. A descriptive study of 449 patients].
AB  - BACKGROUND AND OBJECTIVES: Rhabdomyolysis is a clinical syndrome characterized by
      acute necrosis of skeletal muscles along with the release of breakdown products
      into the bloodstream. Rhabdomyolysis is potentially lethal and its most serious
      complication is acute renal failure (ARF). Diagnosis is established by the 5
      times elevation (975 UI/l) over the upper limit of creatine-kinase (CK). PATIENTS
      AND METHODS: We performed a retrospective study on Salamanca University Hospital
      for the period 1999-2010. There were 449 patients diagnosed with rhabdomyolysis
      over which we tested demographic, etiologic, analytic, complication and mortality
      variables. RESULTS: Out of 449 patients, 69% were male. Average age was 66.5 +/-
      21 years. Most frequent etiologies were trauma, sepsis and immobility/crushing
      (24, 19 and 17% respectively). Maximum levels of CK were 343,170 ng/ml and its
      increase did not show significant association with mortality or ARF. This was
      found in 54% of patients (mean creatinine 3.03 mg/dl) and it was significantly
      associated with mortality (P <. 001). Global mortality was 18.7%. There were no
      significant associations between mortality and unique or multiple causes.
      However, there were significant associations between mortality and age (P <. 001)
      and 90% of deaths occurred among patients over 60 years old. CONCLUSION:
      Rhabdomyolysis prevails in elder males. Trauma, sepsis and immobility/crushing
      are the most frequent etiologies. CK values are not related with ARF or
      mortality. Mortality is associated with most frequent causes, old age and ARF.

PMID- 21939989
TI  - [Pleural effusion following aorto-coronary bypass revascularization surgery].

PMID- 21939990
TI  - [Validation of the FINDRISC (FINnish Diabetes RIsk SCore) for prediction of the
      risk of type 2 diabetes in a population of southern Spain. Pizarra Study].
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to validate the ability of
      the Finnish Diabetes Risk Score (FINDRISC) to predict the risk of DM2 in a
      population of south-eastern Spain (Pizarra Study). SUBJECTS AND METHODS: The
      Pizarra Study is a population-based prospective study developed in the town of
      Pizarra (Malaga). The first phase of the study was conducted in 1997-1998,
      including 1051 individuals aged 18-65 years randomly selected from the municipal
      census of the town. In 2003-2004 the subjects participating in the first study
      were reassessed. 824 individuals completed the second phase of the study (78.4%).
      All participants without known diabetes underwent an oral glucose tolerance test
      both at baseline and follow-up. We evaluated the ability of the FINDRISC to
      detect undiagnosed DM2 (first phase: cross-sectional study) and in predicting the
      incidence of DM2 (second phase: cohort study). RESULTS: The test showed good
      results both to detect undiagnosed DM2 (ROC-AUC 0.74) and to predict incident DM2
      (ROC-AUC 0.75). The best prediction of risk of incident DM2 was found in those
      subjects with fasting glucose >100mg/dl and a FINDRISC >=9 (OR: 19.37; 95%IC:
      8,86-42,34; P<.0001). CONCLUSIONS: The results of our study show that FINDRISC
      can be a useful tool to detect subjects at high risk of diabetes in this
      population.

PMID- 21939991
TI  - [Left ventricular mass, diastolic function and collagen metabolism biomarkers in
      essential hypertension].
AB  - BACKGROUND AND OBJECTIVE: To evaluate the association between circulating
      biomarkers of collagen metabolism in serum, left ventricular mass index (LVMI)
      and diastolic dysfunction in patients with resistant hypertension. PATIENTS AND
      METHODS: Fifty-two patients with resistant hypertension and 24 healthy
      individuals were included. The following biomarkers of collagen metabolism were
      analyzed by ELISA: carboxy-terminal propeptide of procollagen type I (PICP) and
      transforming growth factor beta1 (TGFbeta1). The biomarker C-terminal telopeptide
      of collagen type-I (ICTP) was assayed by electrochemiluminescence immunoassay. In
      the patient's group a record of 24-h blood pressure monitoring was obtained and
      an echocardiography was performed. Left ventricular mass was measured according
      to the formula of Devereux and the diastolic function according to the relation
      of E and A waves and mitral propagation velocity. RESULTS: Hypertensive patients
      showed higher levels of PICP and lower levels of ICTP than controls: 83.7 (24.7)
      vs. 55.0 (8.7), P<.0001; and 175.0 (136.4) vs. 323.3 (121.3), P<.0001).
      Hypertensive patients showed a significant relationship between PICP and LVMI
      (r=0.631, P<.0001) and between PICP and diastolic dysfunction (r=-0.519,
      P<.0001). The groups with and without hypertrophy, and with or without diastolic
      dysfunction, differed in the mentioned peptides but not in BP values.
      CONCLUSIONS: Our findings suggest that the analyzed markers of synthesis and
      degradation of collagen may be related to myocardial hypertrophy and diastolic
      dysfunction independent of blood pressure values.

PMID- 21939992
TI  - [Precocious pseudopuberty after accidental exposure to topical testosterone].

PMID- 21939993
TI  - [Pharmacokinetics interaction between methadone and metamizole: study of 53
      cases].

PMID- 21939994
TI  - [New technologies and strategies related to safety of pharmacotherapy].

PMID- 21939995
TI  - [Use of herbal remedies among HIV-infected patients: patterns and correlates].
AB  - BACKGROUND AND OBJECTIVE: To evaluate the prevalence and patterns of use of
      herbal remedies among HIV-infected patients, and to identify potential health
      risks and correlates associated with the use of these products. PATIENTS AND
      METHODS: Cross-sectional survey including 1000 HIV-infected outpatients in
      Barcelona. Participants completed a questionnaire on the use of herbal remedies
      and other types of complementary treatments within the previous year as well as
      on sociodemographic and clinical characteristics. Herbal users' questionnaires
      were scrutinized for potential adverse effects and drug interactions with
      antiretroviral treatment. Correlates of use of herbal remedies were evaluated
      through logistic regression analyses. RESULTS: One third of patients (n=355) had
      used herbal remedies, but doctors were informed about such a use by only 69
      (19.4%) herbal users. Potential health problems were identified in 193 (54.4%)
      cases. Herbal remedy use was related to a history of ever discussing
      complementary and alternative medicine use with the physician (OR: 3.12; 95% CI:
      2.30-4.23), having a secondary-school or higher education (OR: 2.63; 95% CI: 1.78
      3.88), and perception of complementary therapies as effective (OR: 2.28; 95% CI:
      1.18-4.41). Other factors were non-Caucasian ethnicity (OR: 1.65; 95% CI: 1.07
      2.56) and the presence of non-HIV-related symptoms (OR: 1.68; 95% CI: 1.24-2.28).
      CONCLUSIONS: Herbal remedy use is common among HIV-infected patients. HIV
      caregivers and patients should be sensitized to potential risks and the use of
      these remedies should be routinely monitored in clinical practice.

PMID- 21939996
TI  - [Acute coronary syndrome in women. Gender differences].
AB  - BACKGROUND AND OBJECTIVE: Our aims was to investigate possible gender differences
      in the diagnostic assessment, treatment and prognosis of patients admitted with
      acute coronary syndrome (ACS). PATIENTS AND METHODS: Prospective study of a
      cohort of 396 patients consecutively admitted to the coronary unit in the period
      of 18 months with the diagnoses of ACS. We divided the sample into two groups
      based on gender: 294 men and 102 women. We analysed the diagnostic assessment,
      hospital treatment, coronary revascularization (ICP), appearance of heart failure
      (HF) and in-hospital and 1-year mortality. We analyzed predictors of mortality in
      a multivariate model. RESULTS: Women were older (70.9+/-11.9 versus 64.4+/-12.0;
      P<.001) and had more comorbidities such as hypertension (70.5% versus 53.7%;
      P=.003), diabetes (51.0% versus 33.3%; P<.01) and HF (20.5% versus 9.1%; P<.01)
      than men, while men had greater frequency of smoking (54.42% versus 13.73%;
      P<.001). Women had higher incidence of cardiogenic shock on admission. There were
      no differences in thrombolysis and women did not have a different pattern of
      access to coronary angiography, but men had greater frequency of ICP (50.8%
      versus 34.6%; P<.01). Women were more likely to develop a higher in-hospital HF
      (32.6% versus 25.9%; P<.05) and in-hospital mortality (17.6% versus 4.7%;
      P<.001). In the multivariate analyses, HF on admission OR 8.98 (3.29-24.47),
      older age OR 1.07 (1.01-1.13) and female gender OR 3.14 (1.27-7.74), were
      independent predictors of in-hospital mortality. CONCLUSIONS: In our study,
      female gender was an independent predictor of in-hospital mortality in patients
      with ACS.

PMID- 21939997
TI  - [Biochemical diagnosis of left ventricular remodelling in refractory
      hypertension].

PMID- 21939998
TI  - [Surgical treatment of symptomatic polycystic liver disease, an uncommon problem
      without systematic approach].

PMID- 21939999
TI  - [Influence of patients' age in the probabilistic models of mortality on admission
      in general internal medicine wards].
AB  - BACKGROUND AND OBJECTIVE: The predictive models of in-hospital mortality in the
      departments of Internal Medicine have not reached a generalized use. Our
      hypothesis is that the very elderly patients interfere in the models currently in
      use. PATIENTS AND METHOD: In this observational, prospective cohort study, 1,500
      patients admitted consecutively in the department of Internal Medicine were
      analysed. A logistic regression analysis based on the REMS model was used for the
      whole series and after segmenting it according to if the age of patients was 85
      years or less, or more than 85 years. RESULTS: The global in-hospital mortality
      of the patients was 12%. Although the REMS model predicted a global mortality of
      11.9%, sensitivity and specificity for an individual prediction were not
      satisfactory because the AUC was only 0.704. When the sample was split according
      to the age of patients, the model gained precision for the group <= 85 years (AUC
      0.799), whereas it lost sensitivity and specificity for the group of patients >
      85 years (AUC 0.66). CONCLUSIONS: Age of patients interferes in the general
      models of prediction of mortality in departments of Internal Medicine. There may
      be important variables in advanced age not taken into account in the predictive
      models nowadays available. We think that specific predictive models of in
      hospital mortality in Internal Medicine should be designed for patients of
      advanced age.

PMID- 21940000
TI  - [Computerized physician order entry, medication use and patient safety].

PMID- 21940001
TI  - [Prevalence of atrial fibrillation and related factors in hospitalized old
      patients: ESFINGE study].
AB  - BACKGROUND AND OBJECTIVES: Atrial fibrillation (AF) is the commonest rhythm
      abnormality and it increases with ageing. The main objective of this study was to
      assess the prevalence of AF in hospitalized old patients as well as its
      characteristics and related clinical and therapeutic factors. PATIENTS AND
      METHODS: Prospective, multicenter, observational study in patients aged >= 70
      years with AF, who had been hospitalized in Internal Medicine or Geriatrics
      wards. All variables studied were obtained from the patients' clinical records.
      RESULTS: Out of 3,319 evaluable patients, 922 had an AF, which represents a
      prevalence of 31.3% (CI 95%; 29.7-32.9). The mean age was 82 years (6.1; 69.9
      101.8) and 57% were women. 88.7% of patients (818 p) had an AF before admission.
      AF was long-standing persistent or permanent in 728 cases (89.1%) and it was the
      first episode (paroxysmal or persistent) in 51 patients (6.2%). There was a clear
      etiology of AF in only 4.1% cases. Congestive heart failure was the commonest
      reason for hospitalization in our patients. Regarding the cardiovascular risk
      factors, 80.3% patients were hypertensive, 36.4% had dyslipemia, 38.2% had
      diabetes and 5% were active smokers. Associated diseases included renal
      insufficiency (38.1%) and chronic obstructive pulmonary disease (38.2%); in
      addition, 188 patients (20.4%) had suffered from cerebrovascular accidents.
      Finally, 67.4% patients had received antiarrhythmic drugs for their FA. Although
      86.1% had received thromboembolic prevention therapy, only 54.1% were under oral
      anticoagulation. Finally, 6.9% patients had antiarrhythmic drugs-related side
      effects. CONCLUSIONS: Over one third of hospitalized patients older than 70 years
      have AF, which is generally relapsing and permanent. Heart failure is the
      commonest reason for hospitalization in these patients and about 40% have an
      associated disease.

PMID- 21940002
TI  - [First world case of -alpha3,7-associated Hb J-Camaguey].

PMID- 21940003
TI  - [Home hospitalization directly from emergency department: an efficient
      alternative to standard inpatient hospitalization].
AB  - BACKGROUND AND OBJECTIVE: To compare technical quality, patient health outcomes,
      and satisfaction degree of patients admitted to hospital at home (HAH) from the
      emergency department (ED) with those with standard hospitalization (SH). PATIENTS
      AND METHODS: Comparative prospective study. Medical records of patients admitted
      to the HAH were reviewed and then they were also called and surveyed. The
      following variables were recorded: demographic and clinical aspects, patient
      health status at the time of phone survey, technical and perceived quality.
      RESULTS: Patients included: 111 (65 from the ED and 46 from the SH). Phone survey
      was performed to 76 patients and 57 carers. Length of stay was significantly
      shorter in patients from the ED compared with those from SH (1.02 +/- 0.44 vs
      2.23 +/- 0.94 days, P<.0005). No other differences were observed in patients'
      demographics, clinical aspects and health status, in technical quality, and in
      perceived quality between both groups. CONCLUSION: When HAH is an option, these
      results seem to indicate that patient hospital stay can be shortened if HAH
      admittance is obvious, after a period of patient treatment and stabilization,
      from the ED instead from HAH.

PMID- 21940004
TI  - [Ataxia-telangiectasia].

PMID- 21940005
TI  - [Alternative medicine and AIDS: towards a more effective communication concerning
      medicinal plants].

PMID- 21940006
TI  - [Endothelial dysfunction and circulating microparticles in patients with
      antiphospholipid antibodies].

PMID- 21940007
TI  - [Nonbacterial thrombotic endocarditis and severe aortic valve regurgitation.
      Resolution after chemotherapy].

PMID- 21940008
TI  - [Percutaneous closure of left atrial appendage. A therapeutic option in patients
      with atrial fibrillation and esophageal varices and high risk of haemorrage].

PMID- 21940009
TI  - [Topiramate-induced bilateral acute angle closure glaucoma and myopia].

PMID- 21940010
TI  - [65 year old woman with fever during three weeks, constitutional syndrome and
      headache].

PMID- 21940011
TI  - [Polyglandular autoimmune syndrome type 1. Different onset forms].

PMID- 21940012
TI  - [Beer potomania. An uncommon cause of severe hyponatremia].

PMID- 21940013
TI  - [Atrial fibrillation in elderly. That long way...].

PMID- 21940014
TI  - [Prophylactic treatment with rituximab in thrombotic thrombocytopenic purpura].

PMID- 21940015
TI  - [Towards a better awareness of Clostridium difficile-associated infection].

PMID- 21940017
TI  - [An unusual cause of acute appendicitis].

PMID- 21940018
TI  - [Eccema herpeticum].

PMID- 21940020
TI  - [Dhat syndrome: report of six cases].

PMID- 21940021
TI  - [Left atrial appendage closure by using endovascular plugs].

PMID- 21940022
TI  - Stemodin-derived analogues with lipid peroxidation, cyclooxygenase enzymes and
      human tumour cell proliferation inhibitory activities.
AB  - A series of analogues, derived from the antiviral and cytotoxic diterpene
      stemodin, were prepared and evaluated for their lipid peroxidation (LPO),
      cyclooxygenase enzyme-1 (COX-1) and -2 (COX-2), and tumour cell proliferation
      inhibitory activities. Oxidation of stemodin produced stemodinone, which was then
      converted to stemod-12-en-2-one. Reaction of the latter under Petrow conditions
      (bromine; silver acetate/pyridine) yielded mainly dibrominated abeo-stachanes.
      Solvolysis of the dibromo compounds gave products of hydrolysis, some with
      rearranged skeleta. In the lipid peroxidation inhibitory assay three of the
      compounds exhibited prominent activity. Interestingly, all the analogues showed
      higher COX-1 enzyme inhibition than COX-2. Although a few of the diterpenes
      limited the growth of some human tumour cell lines, most compounds induced
      proliferation of such cells.

PMID- 21940023
TI  - [Cystic fibrosis in images: the Bhalla scoring system for computed tomography in
      paediatric patients].
AB  - To monitor the course of lung damage in patients with cystic fibrosis (CF) using
      the different chest X-ray and high resolution computed tomography (HRCT) scoring
      systems that have been developed. The HRCT technique is more sensitive than chest
      radiography to evaluate the anatomy. However, in paediatric patients, the use of
      CT should be kept to a minimum, and guidelines for radiation protection and dose
      reduction should be applied. One of the most used classification systems for HRCT
      is the one proposed by Bhalla in 1991, which helps in the assessment of the
      severity and course of the disease in these patients depending on the different
      imaging findings. We present various examples of these criteria for HRCT,
      observed while reviewing a group of 48 paediatric patients.

PMID- 21940024
TI  - Development and evaluation of enzyme-linked immunosorbent assay based on
      recombinant inorganic pyrophosphatase gene antigen for the detection of
      Mycoplasma suis antibodies.
AB  - The recombinant ppa protein of Mycoplasma suis migrated to 21 kDa. Using this
      antigen, an ELISA system to detect the antibody against M. suis infection in
      swine was established. The rELISA demonstrated 98.5% specificities among negative
      samples and 96.9% sensitivity among positive samples with M. suis infection. A
      comparison of this ELISA system with an indirect hemagglutination assay (IHA)
      test using 132 swine samples revealed that the positive rate was 34.0% in ELISA
      and 28.0% in IHA. Compared with IHA, the present rELISA system using recombinant
      ppa antigen significantly improves the specificity, sensitivity, and stability
      for serodiagnosis of M. suis infection in swine.

PMID- 21940025
TI  - Pathogenic mechanisms of Trypanosoma evansi infections.
AB  - Insect-borne diseases exact a high public health burden and have a devastating
      impact on livestock and agriculture. To date, control has proved to be
      exceedingly difficult. One such disease that has plagued sub-Saharan Africa is
      caused by the protozoan African trypanosomes (Trypanosoma species) and
      transmitted by tsetse flies (Diptera: Glossinidae). This presentation describes
      Trypanosoma evansi (T. evansi) which causes the disease known as trypanosomosis
      (Surra) or trypanosomiasis in which several attempts have being made to unravel
      the clinical pathogenic mechanisms in T. evansi infections, yielding various
      reports which have implicated hemolysis associated to decrease in life span of
      erythrocytes and extensive erythrophagocytosis being among those that enjoy
      prominence. T. evansi generates Adenosine Triphosphate (ATP) from glucose
      catabolism which is required for the parasite motility and survival. Oxidation of
      the erythrocytes induces oxidative stress due to free radical generation. Lipid
      peroxidation of the erythrocytes causes membrane injury, osmotic fragility and
      destruction of the red blood cell (RBC) making anemia a hallmark of the pathology
      of T. evansi infections.

PMID- 21940026
TI  - Effects of different media on proliferation and differentiation capacity of
      canine, equine and porcine adipose derived stem cells.
AB  - Adult stem cells are of particular interest for therapeutic use in the field of
      regenerative medicine. Adipose-derived mesenchymal stem cells (ASCs) are an
      attractive stem cell source for all fields of regenerative medicine because
      adipose tissue - and therewith cells - can easily be harvested from each donor.
      However, common expansion using fetal bovine serum (FBS) can not be used for
      clinical applications as xenogenic proteins must be avoided. Adipose tissue from
      equine, canine and porcine donors was digested with collagenase to isolate ASCs.
      ASCs were either expanded in a cell culture medium supplemented with FBS or in a
      serum-free medium (UltraCulture; UC) supplemented with a serum substitute
      (UltroserG). From all three animal species, the adipogenic and osteogenic
      differentiation potential of ASCs cultured with different media was analyzed in
      vitro. Cell proliferation analysis showed a population doubling time of 48-68 h
      for canine cells, 54-65 h for porcine cells and 54-70 h for equine cells,
      expanded in different media. Except for porcine ASCs, cells cultured in media
      supplemented with FBS grew faster than cells expanded in UC medium with
      UltroserG. Yet, all cells maintained their potential to differentiate into
      adipocytes and osteoblasts. UltraCulture medium containing UltroserG can for all
      examined species be recommended if FBS needs to be avoided in the expansion of
      donor-derived (stem) cells.

PMID- 21940027
TI  - [Intractable epistaxis in Osler-Rendu-Weber syndrome].
AB  - INTRODUCTION: Osler-Rendu-Weber syndrome is an inherited disorder characterized
      by mucocutaneous and visceral telangiectasia. It is often revealed by recurrent
      epistaxis. It is sometimes profuse and intractable. Hemostasis may be
      problematic. CASE STUDY: A 61-year-old male patient presented with severe
      epistaxis due to Osler-Rendu-Weber syndrome. Embolization of the external carotid
      branches was needed for hemostasis. DISCUSSION: Embolization of external carotid
      artery branches can be an effective therapeutic alternative when usual treatments
      fail.

PMID- 21940028
TI  - [Bacteremia of oral origin].
AB  - Transient bacteremia from oral cavity related to oral anaerobic bacteria may
      occur as a result of dental healthcare procedures but also as a result of daily
      gestures involving the gums (chewing and oral hygiene). The risk of presenting a
      transient bacteremia is related to oral cavity bacterial load and to the severity
      of inflammation in the oral cavity. Although bacteremia is transient, in patients
      with immunodeficiency or comorbidity, this bacteremia may cause extra-oral
      infections. The bacteremia rate and the identified bacteria vary from one study
      to the next, depending on the method used to isolate and identify bacteria.
      Nevertheless, the risk for bacteremia is determined by the infectious and
      inflammatory conditions of each patient.

PMID- 21940029
TI  - Nitrogen and phosphorus removal from municipal wastewater effluent using
      microalgal biofilms.
AB  - Microalgal biofilms have so far received little attention as post-treatment for
      municipal wastewater treatment plants, with the result that the removal capacity
      of microalgal biofilms in post-treatment systems is unknown. This study
      investigates the capacity of microalgal biofilms as a post-treatment step for the
      effluent of municipal wastewater treatment plants. Microalgal biofilms were grown
      in flow cells with different nutrient loads under continuous lighting of 230
      MUmol/m(2)/s (PAR photons, 400-700 nm). It was found that the maximum uptake
      capacity of the microalgal biofilm was reached at loading rates of 1.0 g/m(2)/day
      nitrogen and 0.13 g/m(2)/day phosphorus. These maximum uptake capacities were the
      highest loads at which the target effluent values of 2.2 mg/L nitrogen and 0.15
      mg/L phosphorus were still achieved. Microalgal biomass analysis revealed an
      increasing nitrogen and phosphorus content with increasing loading rates until
      the maximum uptake capacities. The internal nitrogen to phosphorus ratio
      decreased from 23:1 to 11:1 when increasing the loading rate. This combination of
      findings demonstrates that microalgal biofilms can be used for removing both
      nitrogen and phosphorus from municipal wastewater effluent.

PMID- 21940030
TI  - Reduced iron induced nitric oxide and nitrous oxide emission.
AB  - Formation of the greenhouse gas nitrous oxide in water treatment systems is
      predominantly studied as a biological phenomenon. There are indications that also
      chemical processes contribute to these emissions. Here we studied the formation
      of nitric oxide (NO) and nitrous oxide (N(2)O) due to chemical nitrite reduction
      by ferrous iron (Fe(II)). Reduction of nitrite and NO coupled to Fe(II) oxidation
      was studied in laboratory-scale chemical experiments at different pH, nitrite and
      iron concentrations. The continuous measurement of both NO and N(2)O emission
      showed that nitrite reduction and NO reduction have different kinetics. Nitrite
      reduction shows a linear dependency on the nitrite concentration, implying first
      order kinetics in nitrite. The nitrite reduction seems to be an equilibrium based
      reaction, leading to a constant NO concentration in the liquid. The NO reduction
      rate is suggested to be most dependent on reactive surface availability and the
      sorption of Fe(II) to the reactive surface. The importance of emission of NO and
      N(2)O coupled to iron oxidation is exemplified by iron reduction experiments and
      several examples of environments where this pathway can play a role.

PMID- 21940031
TI  - Leaching techniques to remove metals and potentially hazardous nutrients from
      trout farm sludge.
AB  - A fish farm sludge high in P (2-6% w/w as dry matter), Fe (5-7%), C (40-50%) and
      N (0.8-4%) was subjected to a series of acid leaching treatments using HCl,
      organic acids, and biologically mediated acid production. Additions of
      biodegradable organic acid solubilized heavy metals better than HCl, while
      additions of 1.5% w/v glucose followed by 7 day incubation stabilized the sludge
      releasing 92% P, 100% Fe. The use of homo-lactic Lactobacillus plantarum starter
      cultures were more effective than hetero-lactic Lactobacillus buchneri,
      solubilizing 81.9% P, 92.2% Fe, 93.0% Zn and 96.4% Ca in the sludge. The
      anaerobic sludge-glucose fermentation using L. plantarum produced a leached
      sludge that has low heavy metal and nutrient content while affording the recovery
      of nutrients. The potential of these methods for practical application are
      briefly discussed.

PMID- 21940032
TI  - Oxygen transfer and uptake, nutrient removal, and energy footprint of parallel
      full-scale IFAS and activated sludge processes.
AB  - Integrated fixed-film activated sludge (IFAS) processes are becoming more popular
      for both secondary and sidestream treatment in wastewater facilities. These
      processes are a combination of biofilm reactors and activated sludge processes,
      achieved by introducing and retaining biofilm carrier media in activated sludge
      reactors. A full-scale train of three IFAS reactors equipped with AnoxKaldnes
      media and coarse-bubble aeration was tested using off-gas analysis. This was
      operated independently in parallel to an existing full-scale activated sludge
      process. Both processes achieved the same percent removal of COD and ammonia,
      despite the double oxygen demand on the IFAS reactors. In order to prevent
      kinetic limitations associated with DO diffusional gradients through the IFAS
      biofilm, this systems was operated at an elevated dissolved oxygen concentration,
      in line with the manufacturer's recommendation. Also, to avoid media coalescence
      on the reactor surface and promote biofilm contact with the substrate, high
      mixing requirements are specified. Therefore, the air flux in the IFAS reactors
      was much higher than that of the parallel activated sludge reactors. However, the
      standardized oxygen transfer efficiency in process water was almost same for both
      processes. In theory, when the oxygen transfer efficiency is the same, the air
      used per unit load removed should be the same. However, due to the high DO and
      mixing requirements, the IFAS reactors were characterized by elevated air flux
      and air use per unit load treated. This directly reflected in the relative energy
      footprint for aeration, which in this case was much higher for the IFAS system
      than activated sludge.

PMID- 21940033
TI  - Effects of silver nanoparticles on wastewater biofilms.
AB  - The goal of this research is to understand the potential antibacterial effect of
      silver nanoparticles (Ag-NPs) on biological wastewater treatment processes. It
      was found that original wastewater biofilms are highly tolerant to the Ag-NP
      treatment. With an application of 200 mg Ag/L Ag-NPs, the reduction of biofilm
      bacteria measured by heterotrophic plate counts was insignificant after 24 h.
      After the removal of loosely bound extracellular polymeric substances (EPS), the
      viability of wastewater biofilms was reduced when treated under the same
      conditions. By contrast, when treated as planktonic pure culture, bacteria
      isolated from the wastewater biofilms were highly vulnerable to Ag-NPs. With a
      similar initial cell density, most bacteria died within 1 h with the application
      of 1 mg Ag/L Ag-NPs. The results obtained here indicate that EPS and microbial
      community interactions in the biofilms play important roles in controlling the
      antimicrobial effects of Ag-NPs. In addition, slow growth rates may enhance the
      tolerance of certain bacteria to Ag-NPs. The effects of Ag-NPs on the entire
      microbial community in wastewater biofilms were analyzed using polymerase chain
      reaction-denaturing gradient gel electrophoresis, PCR-DGGE. The studies showed
      that the microbial susceptibility to Ag-NPs is different for each microorganism.
      For instance, Thiotrichales is more sensitive to Ag-NPs than other biofilm
      bacteria.

PMID- 21940034
TI  - Ozone treatment ameliorates oil sands process water toxicity to the mammalian
      immune system.
AB  - We evaluated whether ozonation ameliorated the effects of the organic fraction of
      oil sands process water (OSPW) on immune functions of mice. Ozonation of OSPW
      eliminated the capacity of its organic fraction to affect various mouse bone
      marrow-derived macrophage (BMDM) functions in vitro. These included the
      production of nitric oxide and the expression of inducible nitric oxide synthase,
      the production of reactive oxygen intermediates and the expression of NADPH
      oxidase subunits, phagocytosis, and the expression of pro-inflammatory cytokine
      genes. Ozone treatment also eliminated the ability of OSPW organic fraction to
      down-regulate the expression of various pro-inflammatory cytokine and chemokine
      genes in the liver of mice, one week after oral exposure. We conclude that ozone
      treatment may be a valuable process for the remediation of large volumes of OSPW.

PMID- 21940035
TI  - The spectrum of Merkel cell polyomavirus expression in Merkel cell carcinoma, in
      a variety of cutaneous neoplasms, and in neuroendocrine carcinomas from different
      anatomical sites.
AB  - Most Merkel cell carcinomas display pure neuroendocrine differentiation (pure
      Merkel cell carcinoma), whereas a minority show combined neuroendocrine and
      nonneuroendocrine elements (combined Merkel cell carcinoma). Recent
      identification of Merkel cell polyomavirus DNA and Merkel cell polyomavirus large
      T antigen expression in a proportion of Merkel cell carcinomas has suggested
      viral-induced oncogenesis. To date, Merkel cell polyomavirus immunohistochemistry
      has shown an absence of viral large T antigen expression in combined Merkel cell
      carcinoma as well as select non-Merkel cell carcinoma cutaneous lesions and
      visceral neuroendocrine tumors. In our series, we aimed to further characterize
      the frequency and pattern of Merkel cell polyomavirus large T antigen expression
      by CM2B4 immunohistochemistry in primary and metastatic Merkel cell carcinoma
      (pure Merkel cell carcinoma and combined Merkel cell carcinoma) and various non
      Merkel cell carcinoma lesions from patients with Merkel cell carcinoma, patients
      without Merkel cell carcinoma, and individuals with altered immune function.
      Merkel cell polyomavirus large T antigen was detected in 17 (63%) of 27 pure
      Merkel cell carcinomas and absent in all 15 (0%) combined Merkel cell carcinomas.
      Furthermore, complete concordance (100%) of Merkel cell polyomavirus large T
      antigen expression was observed in 10 cases of primary Merkel cell carcinoma and
      subsequent tumor metastases. We also evaluated 70 non-Merkel cell carcinoma
      lesions including 15 cases each of pulmonary and gastrointestinal neuroendocrine
      tumors. All 70 non-Merkel cell carcinoma lesions were negative for Merkel cell
      polyomavirus by CM2B4 immunohistochemistry, irrespective of any known Merkel cell
      carcinoma diagnosis and immune status. In summary, our identification of Merkel
      cell polyomavirus large T antigen expression in a subset of Merkel cell carcinoma
      and lack of findings in combined Merkel cell carcinomas and non-Merkel cell
      carcinoma lesions concur with earlier findings and implicate Merkel cell
      polyomavirus-independent pathogenesis in these cases. Overall, CM2B4
      immunohistochemistry appears to be a specific method for Merkel cell polyomavirus
      detection and has the potential to play an important role in the diagnosis and
      classification of Merkel cell carcinoma in the future.

PMID- 21940036
TI  - Epithelial to mesenchymal transition in early stage endometrioid endometrial
      carcinoma.
AB  - Epithelial to mesenchymal transition is thought to be implicated in tumor
      invasion and metastasis. To investigate its role in myometrial invasion, samples
      from 42 stage I (confined to the corpus) endometrioid endometrial carcinomas were
      analyzed. All E-cadherin repressors (SNAI1, SNAI2 (SLUG), ZEB1, HMGA2, and
      TWIST1) had a higher expression in endometrioid endometrial carcinomas than in
      normal endometrium (P < .0001), whereas CDH1 (E-cadherin gene) tended to be
      lower. In comparison with nonmyoinvasive (stage IA) tumors, those with deep
      myometrial invasion (stage IC) had increased messenger RNA expression of SLUG,
      ZEB1, and HMGA2 (P < .001). Furthermore, samples from the myoinvasive front of
      deeply invasive tumors had higher levels of SLUG, ZEB1, and HMGA2 than the
      corresponding superficial samples. Immunohistochemical analysis of these cases
      revealed that the decrease in E-cadherin was concordant with an increase in Snail
      and Twist protein expression. Trying to induce epithelial to mesenchymal
      transition in endometrioid endometrial carcinomas, we initially produced
      persistent activation of this pathway in Ishikawa cells. The cell line was
      infected with lentiviruses carrying the V600E mutation of BRAF, inducing loss of
      beta-catenin, E-cadherin, and cytokeratin and increase in vimentin and Snail.
      These changes were mediated by ERK1/2 phosphorylation, which was also increased
      at the myoinvasive front. Furthermore, MEK1/2 inhibitor UO126 reversed the
      mesenchymal phenotype. Our findings suggest that epithelial to mesenchymal
      transition regulators are implicated in myometrial invasion of endometrioid
      endometrial carcinoma and may be potential therapeutic targets through the
      MAPK/ERK pathway.

PMID- 21940038
TI  - A revised stratigraphic framework for Olduvai Gorge Bed I based on tuff
      geochemistry.
AB  - Olduvai Gorge, Tanzania has rich records of Plio-Pleistocene fauna and flora,
      hominin fossils, and stone artifacts preserved between well-dated tephra layers
      (tuffs). Accurate correlation between sites in the two million year section is
      complicated by faulting, erosion, change in physical appearance of the tuffs, and
      quality of preservation. Traditional tuff geochemical techniques using glass
      cannot be applied because of poor glass preservation, and previous physical
      mapping has led to miscorrelations in Bed I. A new approach, using a combination
      of glass and mineral compositions (feldspar, augite, hornblende, and oxides)
      produced successful geochemical fingerprints for all ten major Bed I (~2.03-1.79
      Ma) tuffs. These fingerprints make available a reliable means for correlating
      specific tuffs between the well-dated "Junction" sites, such as FLK and HWK, and
      less well-dated sites at the basin margins. The new correlations provide a high
      resolution stratigraphic framework for Bed I and correct previous miscorrelations
      in the west of the basin. Olduvai Hominin 65, from western Olduvai, was recovered
      from a level between Tuff IC and the Ng'eju Tuff, and therefore dates to 1.79
      1.84 Ma.

PMID- 21940037
TI  - Loss of expression of the SWI/SNF chromatin remodeling subunit BRG1/SMARCA4 is
      frequently observed in intraductal papillary mucinous neoplasms of the pancreas.
AB  - A better molecular characterization of intraductal papillary mucinous neoplasm
      (IPMN), the most frequent cystic precursor lesion of pancreatic adenocarcinoma,
      may have a pivotal role in its early detection and in the development of
      effective therapeutic strategies. BRG1, a central component of the chromatin
      remodeling complex SWI/SNF regulating transcription, is inactive in several
      malignancies. In this study, we evaluate the Brg1 expression in intraductal
      papillary mucinous neoplasm to better understand its role in the pancreatic
      carcinogenesis. Tissue microarrays of 66 surgically resected IPMNs were
      immunolabeled for the Brg1 protein. Expression patterns were then correlated with
      clinicopathologic parameters. Normal pancreatic epithelium strongly immunolabeled
      for Brg1. Reduced Brg1 expression was observed in 32 (53.3%) of the 60 evaluable
      IPMN lesions and occurred more frequently in high-grade IPMNs (13 of 17 showed
      loss; 76%) compared to intermediate-grade (15 of 29 showed loss; 52%) and low
      grade IPMNs (4 of 14 showed loss; 28%) (P = .03). A complete loss of Brg1
      expression was observed in 5 (8.3%) of the 60 lesions. Finally, a decrease in
      Brg1 protein expression was furthermore found in a low-passage noninvasive IPMN
      cell line by Western blot analysis. We did not observe correlation between Brg1
      expression and IPMN subtype or with location of the cyst. We provide first
      evidence that Brg1 expression is lost in noninvasive cystic precursor lesions of
      pancreatic adenocarcinoma.

PMID- 21940039
TI  - Development of spatial water resources vulnerability index considering climate
      change impacts.
AB  - This study developed a new framework to quantify spatial vulnerability for
      sustainable water resources management. Four hydrologic vulnerability indices-
      potential flood damage (PFDC), potential drought damage (PDDC), potential water
      quality deterioration (PWQDC), and watershed evaluation index (WEIC)--were
      modified to quantify flood damage, drought damage, water quality deterioration,
      and overall watershed risk considering the impact of climate change,
      respectively. The concept of sustainability in the Driver-Pressure-State-Impact
      Response (DPSIR) framework was applied in selecting all appropriate indicators
      (criteria) of climate change impacts. In the examination of climate change,
      future meteorological data was obtained using CGCM3 (Canadian Global Coupled
      Model) and SDSM (Statistical Downscaling Model), and future stream run-off and
      water quality were simulated using HSPF (Hydrological Simulation Program -
      Fortran). The four modified indices were then calculated using TOPSIS, a multi
      attribute method of decision analysis. As a result, the ranking obtained can be
      changed in consideration of climate change impacts. This study represents a new
      attempt to quantify hydrologic vulnerability in a manner that takes into account
      both climate change impacts and the concept of sustainability.

PMID- 21940040
TI  - Effective radiation exposure in evaluation and follow-up of patients with
      urolithiasis.
AB  - OBJECTIVE: To quantify the effective radiation dose associated with the
      evaluation and follow-up of patients with urolithiasis. METHODS: Retrospective
      review was performed for consecutive patients presenting to a tertiary stone
      clinic with acute stone episodes between November 2007 and December 2008, and had
      at least 2 years of follow-up. Number and modality of imaging studies were
      collected. Effective radiation exposure (ERE) doses were calculated from the dose
      length product values reported with each computed tomography (CT) scan. RESULTS:
      There were 72 males and 32 females with a mean age of 49 years (range 21-78).
      Patients underwent an average 1.8 (range 0-5) and 0.7 (range 0-2) plain
      radiographs, 0.82 (range 0-4) and 0.15 (range 0-2) CTs, 0.09 (range 0-1) and 0.03
      (range 0-1) intravenous urograms, and 0.3 (range 0-1) and 0.6 (range 0-2)
      ultrasounds (US) during the first and second years, respectively (all P<.05). The
      average calculated ERE dose per CT scan was 23.16 mSv (range 4.94-72.77). The
      calculated mean ERE dose per patient significantly decreased from 29.29 mSv
      (range 1.7-77.27) in the first year to 8.04 mSv (range 1.4-24.72) in the second
      year (P<.01). This was because of significantly fewer CT scans and significantly
      more US imaging during the second year (P<.05). Although 18 (17.3%) patients
      exceeded 50 mSv during the first year, none exceeded this threshold during the
      second year. The mean ERE dose did not correlate with stone location, patient
      age, and sex. CONCLUSION: The calculated mean ERE dose significantly decreased
      during the second year of follow-up in patients with urolithiasis because of
      significantly higher use of US.

PMID- 21940041
TI  - Robotic transperineal prostate biopsy: pilot clinical study.
AB  - OBJECTIVE: To develope a robot (BioXbot) that performs mapping transperineal
      prostate biopsy (PB) with two perineal skin punctures under ultrasound guidance.
      Our pilot study's clinical endpoints were complications and its technical
      endpoints were the duration for each phase. METHODS: This institution review
      board-approved prospective clinical trial included patients with indications for
      PB. Two urologists performed these PBs. In the lithotomy position and under
      general anesthesia, the transrectal biplane ultrasound probe acquired transverse
      images of the prostate gland. The urologist defined its boundaries and planned
      the biopsy. It guided the PB in 3 axes, passing through a single perineal skin
      puncture for each prostate side. After each biopsy, it automatically moved to the
      next position. The steps were repeated on the contralateral side. RESULTS: Our 20
      patients had a mean prostate-specific antigen of 8.4 +/- 4.9 ng/mL. Two patients
      had 2 previous biopsies, whereas the rest had one. The mean number of biopsies
      taken was 28.5 +/- 6.2 in a mean total procedure time of 32.5 +/- 3.2 minutes. We
      detected 3 patients with prostate cancer with Gleason score 3 + 3. Two patients
      required brief bladder catheterization after their biopsy. Their prostate volumes
      were >50 mL and the number of biopsies taken was >30 cores. There was no
      mechanical failure, sepsis, bleeding per-rectal, or perineal hematoma.
      CONCLUSION: This pilot study demonstrated BioXbot's safety and feasibility as a
      biopsy platform. It can potentially be used for image-guided PB and focal
      therapy.

PMID- 21940042
TI  - Benign testicular enlargement due to diffuse interstitial fibrosis associated
      with cryptorchid testis in 11-month-old boy.
AB  - Benign testicular enlargement secondary to diffuse interstitial fibrosis is a
      rare clinical entity, especially in pediatric patients. To our knowledge, this is
      the first pediatric case reported of benign testicular enlargement due to
      interstitial fibrosis in a cryptorchid testis. We report a rare case of an 11
      month-old boy with a cryptorchid testis found intraoperatively to have an
      asymmetrically enlarged testis secondary to diffuse, benign interstitial fibrosis
      of the testis. Additionally, we discuss previous case reports of testicular
      enlargement due to interstitial fibrosis, the potential etiology and the
      management.

PMID- 21940043
TI  - Simple, safe, and successful evacuation of severe organized clot retention using
      a catheter connected with wall suction: suction and fishing method.
AB  - OBJECTIVE: To introduce a novel method to successfully remove organized hematoma.
      Endoscopic evacuation can be troublesome in some patients with a large amount of
      blood clots or organized hematoma. METHODS: We retrospectively reviewed medical
      records of 15 patients who were treated with a so-called "suction and fishing
      method" for severe clot retention. A large-bore catheter connected with a wall
      suction unit was inserted into the bladder through the resectoscope sheath, and
      subsequently a large volume of urine retention and quite a substantial amount of
      soft clots were removed (suction step). After awhile, negative pressure could not
      work when the catheter met large and organized fragments of blood clots. In this
      situation, large blood clots hanging on the catheter tip were removed by gently
      removing the catheter (fishing step). RESULTS: In all patients, clot retention
      was successfully managed with this method. Clot evacuation was performed without
      anesthesia in 9 patients when electrocauterization was not planned, and opioid
      analgesics were sufficient for pain control. In the other 6 patients, clot
      evacuation and fulguration were performed under anesthesia. Median time for clot
      evacuation was 20 minutes (range 5-55) and median estimated volume of clot
      evacuated was 200 mL (range 50-600). There was no procedure-related complication
      such as bladder rupture. CONCLUSION: The suction and fishing method is a simple,
      safe, and successful way to evacuate severe organized clot retention. It can
      resolve intractable clot retention and rapidly relieve related symptoms without
      anesthesia.

PMID- 21940044
TI  - Long term performance of polycaprolactone vascular grafts in a rat abdominal
      aorta replacement model.
AB  - In the active field of vascular graft research, polycaprolactone is often used
      because of its good mechanical strength and its biocompatibility. It is easily
      processed into micro and nano-fibers by electrospinning to form a porous, cell
      friendly scaffold. However, long term in vivo performance of polycaprolactone
      vascular grafts had yet to be investigated. In this study, polycaprolactone micro
      and nano-fiber based vascular grafts were evaluated in the rat abdominal aorta
      replacement model for 1.5, 3, 6, 12, and 18 months (n = 3 for each time point).
      The grafts were evaluated for patency, thrombosis, compliance, tissue
      regeneration, and material degradation. Results show excellent structural
      integrity throughout the study, with no aneurysmal dilation, and perfect patency
      with no thrombosis and limited intimal hyperplasia. Endothelialization, cell
      invasion, and neovascularization of the graft wall rapidly increased until 6
      months, but at 12 and 18 months, a cellular regression is observed. On the medium
      term, chondroid metaplasia takes place in the intimal hyperplasia layers, which
      contributes to calcification of the grafts. This study presents issues with
      degradable vascular grafts that cannot be identified with short implantation
      times or in vitro studies. Such findings should allow for better design of next
      generation vascular grafts.

PMID- 21940045
TI  - Specific labelling of cell populations in blood with targeted immuno
      fluorescent/magnetic glyconanoparticles.
AB  - Current performance of iron oxide nanoparticle-based contrast agents in clinical
      use is based on the unspecific accumulation of the probes in certain organs or
      tissues. Specific targeted biofunctional nanoparticles would significantly
      increase their potential as diagnostic and therapeutic tools in vivo. In this
      study, multimodal fluorescent/magnetic glyco-nanoparticles were synthesized from
      gold-coated magnetite (glyco-ferrites) and converted into specific probes by the
      covalent coupling of protein G and subsequent incubation with an IgG antibody.
      The immuno-magnetic-fluorescent nanoparticles were applied to the specific
      labelling of peripheral blood mononuclear cells (PBMCs) in a complex biological
      medium, as human blood. We have been able to label specifically PBMCs present in
      blood in a percentage as low as 0.10-0.17%. Red blood cells (RBCs) were also
      clearly labelled, even though the inherent T(2) contrast arising from the high
      iron content of these cells (coming mainly from haemoglobin). The labelling was
      further assessed at cellular level by fluorescence microscopy. In conclusion, we
      have developed new contrast agents able to label specifically a cell population
      under adverse biological conditions (low abundance, low intrinsic T(2), high
      protein content). These findings open the door to the application of these probes
      for the labelling and tracking of endogenous cell populations like metastatic
      cancer cells, or progenitor stem cells that exist in very low amount in vivo.

PMID- 21940046
TI  - Emotion recognition in fathers and mothers at high-risk for child physical abuse.
AB  - OBJECTIVE: The present study was designed to determine whether parents at high
      risk for physical child abuse, in comparison with parents at low risk, show
      deficits in emotion recognition, as well as to examine the moderator effect of
      gender and stress on the relationship between risk for physical child abuse and
      emotion recognition. METHODS: Based on their scores on the Abuse Scale of the CAP
      Inventory (Milner, 1986), 64 parents at high risk (24 fathers and 40 mothers) and
      80 parents at low risk (40 fathers and 40 mothers) for physical child abuse were
      selected. The Subtle Expression Training Tool/Micro Expression Training Tool
      (Ekman, 2004a, 2004b) and the Diagnostic Analysis of Nonverbal Accuracy II
      (Nowicki & Carton, 1993) were used to assess emotion recognition. RESULTS: As
      expected, parents at high risk, in contrast to parents at low risk, showed
      deficits in emotion recognition. However, differences between high- and low-risk
      participants were observed only for fathers, but not for mothers. Whereas fathers
      at high risk for physical child abuse made more errors than mothers at high risk,
      no differences between mothers at low risk and fathers at low risk were found. No
      interaction between stress, gender, and risk status was observed for errors in
      emotion recognition. CONCLUSIONS AND PRACTICE IMPLICATIONS: The present findings,
      if confirmed with physical abusers, could be helpful to further our understanding
      of deficits in processing information of physically abusive parents and to
      develop treatment strategies specifically focused on emotion recognition.
      Moreover, if gender differences can be confirmed, the findings could be helpful
      to develop specific treatment programs for abusive fathers.

PMID- 21940047
TI  - Evidence supporting restrictions on uses of body diagrams in forensic interviews.
AB  - OBJECTIVE: This study compared two methods for questioning children about
      suspected abuse: standard interviewing and body-diagram-focused (BDF)
      interviewing, a style of interviewing in which interviewers draw on a flip board
      and introduce the topic of touching with a body diagram. METHODS: Children
      (N=261) 4-9 years of age individually participated in science demonstrations
      during which half the children were touched two times. Months later, parents read
      stories to their children that described accurate and inaccurate information
      about the demonstrations. The stories for untouched children also contained
      inaccurate descriptions of touching. The children completed standard or BDF
      interviews, followed by source-monitoring questions. RESULTS: Interview format
      did not significantly influence (a) children's performance during early interview
      phases, (b) the amount of contextual information children provided about the
      science experience, or (c) memory source monitoring. The BDF protocol had
      beneficial and detrimental effects on touch reports: More children in the BDF
      condition reported experienced touching, but at the expense of an increased
      number of suggested and spontaneous false reports. CONCLUSIONS: The two props
      that are characteristic of BDF interviewing have different effects on testimonial
      accuracy. Recording answers on a flip board during presubstantive phases does not
      influence the quality of information that children provide. Body diagrams,
      however, suggest answers to children and elicit a concerning number of false
      reports. PRACTICE IMPLICATIONS: Until research identifies procedures and/or case
      characteristics associated with accurate reports of touching during diagram
      assisted questioning, interviewers should initiate discussions about touching
      with open-ended questions delivered without a body diagram.

PMID- 21940048
TI  - Bridge over troubled water: using implementation science to facilitate effective
      services in child welfare.
AB  - To maximize benefits to children and their families, effective practices need to
      be used competently in child welfare settings. Since the 1990s, researchers and
      policy makers have focused attention on empirically supported interventions
      (ESIs). Much less attention has been paid to what is needed to implement these in
      a range of real-world settings. Without proper implementation, which includes an
      evaluation strategy from feasibility to fidelity to on-going work on moderators
      and mediators of program effects, established effective programs can be rendered
      ineffective in practical application. The paper will touch on progress, to date,
      of implementation science, its application to child welfare programs and
      practices, and will highlight a set of practical strategies for implementing
      empirically supported interventions in child welfare.

PMID- 21940049
TI  - Contextual and individual-level predictors of abused children's reentry into out
      of-home care: a multilevel mixture survival analysis.
AB  - OBJECTIVES: This study examined the effects of individual and contextual factors
      on reentry into out-of-home care among children who were discharged from child
      protective services in fiscal year 2004-2005. The objectives were to: (1) examine
      individual and contextual factors associated with reentry, (2) explore whether
      there are meaningful groups of youth who differ in terms of risk for reentry, and
      (3) determine whether relatively homogeneous clusters of child welfare agencies,
      based on contextual characteristics, differ significantly in terms of the reentry
      rates of the children whom they serve. METHOD: The study design involved a
      multilevel longitudinal analysis of administrative data based on an exit cohort.
      Two Cox proportional hazards multilevel mixture models were tested. The first
      model included multiple individual level predictors and no agency level
      predictors. The second model included both levels of predictors. RESULTS: The
      results of multilevel Cox regression mixture modeling indicated that at the
      individual level, younger age, being placed in out-of-home care because of
      neglect and having physical, health problems corresponded to a decreased
      likelihood for reentry. At the agency level, lower average expenditures per child
      and contracting out case management services were associated with faster reentry
      into out-of-home care. CONCLUSIONS: This study demonstrates that children who
      reenter out-of-home care appear to be a homogeneous population and that reentry
      is associated with both contextual factors and individual characteristics.
      PRACTICE IMPLICATIONS: The most important implication that can be drawn from the
      study findings is that reentry may be most effectively prevented by focusing on
      such factors at the organizational level as contracting out case management
      services and funding allocation. Child welfare agencies that are responsible for
      an array of services and decide to contract out case management should consider
      the use of performance-based contracts and emphasize and strengthen quality
      assurance approaches for contracted services. In addition, to compensate for
      lower funding allocated for children served in out-of-home care, child welfare
      workers should become more familiar with community resources and help connect
      families to these supports.

PMID- 21940050
TI  - Characterization of circulating and monocyte-derived dendritic cells in obese and
      diabetic patients.
AB  - Dendritic cells (DCs) are suspected to be involved in the development of
      atherogenesis, but their role is still unclear. The aim of this study was to
      characterize circulating DCs and monocyte-derived DCs (Mo-DCs) of obese and
      diabetic patients (T2D), and to study their interaction with human coronary
      smooth muscle cells (CASMCs). Obese post-menopausal women with or without insulin
      resistance were enrolled and were compared to age-matched healthy women. Myeloid
      circulating DCs significantly increased in obese T2D patients compared to healthy
      donors and a smaller increase was observed for plasmacytoid one. Mature Mo-DCs
      from obese T2D patients significantly decreased when compared to control, but
      they were significantly more capable of adhering to CASMCs compared to that from
      healthy controls and from not-T2D obese subjects. Altogether these data suggest
      that in conditions of insulin-resistance and obesity there is an up-regulation of
      myeloid DCs that might contribute to pathological vascular remodeling.

PMID- 21940051
TI  - Dynamics of human foveal development after premature birth.
AB  - PURPOSE: To determine the dynamic morphologic development of the human fovea in
      vivo using portable spectral domain-optical coherence tomography (SD-OCT).
      DESIGN: Prospective, observational case series. PARTICIPANTS: Thirty-one
      prematurely born neonates, 9 children, and 9 adults. METHODS: Sixty-two neonates
      were enrolled in this study. After examination for retinopathy of prematurity
      (ROP), SD-OCT imaging was performed at the bedside in nonsedated infants aged 31
      to 41 weeks postmenstrual age (PMA) (= gestational age in weeks + chronologic
      age) and at outpatient follow-up ophthalmic examinations. Thirty-one neonates met
      eligibility criteria. Nine children and nine adults without ocular pathology
      served as control groups. Semiautomatic retinal layer segmentation was performed.
      Central foveal thickness, foveal to parafoveal (FP) ratio (central foveal
      thickness divided by thickness 1000 MUm from the foveal center), and 3
      dimensional thickness maps were analyzed. MAIN OUTCOME MEASURES: In vivo
      determination of foveal morphology, layer segmentation, analysis of subcellular
      changes, and spatiotemporal layer shifting. RESULTS: In contrast with the adult
      fovea, several signs of immaturity were observed in the neonates: a shallow
      foveal pit, persistence of inner retinal layers (IRLs), and a thin photoreceptor
      layer (PRL) that was thinnest at the foveal center. Three-dimensional mapping
      showed displacement of retinal layers out of the foveal center as the fovea
      matured and the progressive formation of the inner/outer segment band in the
      opposite direction. The FP-IRL ratios decreased as IRL migrated before term and
      minimally after that, whereas FP-PRL ratios increased as PRL subcellular elements
      formed closer to term and into childhood. A surprising finding was the presence
      of cystoid macular edema in 58% of premature neonates that appeared to affect
      inner foveal maturation. CONCLUSIONS: This study provides the first view into the
      development of living cellular layers of the human retina and of subcellular
      specialization at the fovea in premature infant eyes using portable SD-OCT. Our
      work establishes a framework of the timeline of human foveal development,
      allowing us to identify unexpected retinal abnormalities that may provide new
      keys to disease activity and a method for mapping foveal structures from infancy
      to adulthood that may be integral in future studies of vision and visual cortex
      development. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be
      found after the references.

PMID- 21940052
TI  - Compartmentalized secretory leukocyte protease inhibitor expression and hormone
      responses along the reproductive tract of postmenopausal women.
AB  - Immunity and hormonal responses in the reproductive tissues of postmenopausal
      women are poorly understood. Secretory leukocyte protease inhibitor (SLPI), a
      multifunctional antimicrobial protein expressed at mucosal surfaces, is thought
      to play a key role in infectious and inflammatory contexts. The aim of this study
      was to measure SLPI production along the female reproductive tract in
      postmenopausal women with and without hormonal treatment. We additionally
      quantified estrogen receptor alpha (ERalpha) and progesterone receptor A (PRA) in
      these tissues. Expression of SLPI was decreased in the vagina and ectocervix of
      women under hormonal treatment. Endocervical ERalpha mRNA expression was
      increased while this did not reach significance at the protein level. SLPI
      expression in the endometrium was not influenced by hormonal treatment. We
      observed attenuated ERalpha expression in the cervix and endometrium of
      hormonally treated women, whereas vaginal expression was increased. PRA
      expression was augmented in the cervix and endometrium and unchanged in the
      vagina. Taken together, our results indicate that hormonal responses and receptor
      expression are differentially regulated in vaginal tissue compared with the
      cervix and endometrium.

PMID- 21940053
TI  - Odour recognition memory and odour identification in patients with mild and
      severe major depressive disorders.
AB  - Olfactory deficits, in detection, recognition and identification of odorants have
      been documented in ageing and in several neurodegenerative and psychiatric
      conditions. However, olfactory abilities in Major Depressive Disorder (MDD) have
      been less investigated, and available studies have provided inconsistent results.
      The present study assessed odour recognition memory and odour identification in
      two groups of 12 mild MDD patients (M age 41.3, range 25-57) and 12 severe MDD
      patients (M age, 41.9, range 23-58) diagnosed according to DSM-IV criteria and
      matched for age and gender to 12 healthy normal controls. The suitability of
      olfactory identification and recognition memory tasks as predictors of the
      progression of MDD was also addressed. Data analyses revealed that Severe MDD
      patients performed significantly worse than Mild MDD patients and Normal controls
      on both tasks, with these last groups not differing significantly from one
      another. The present outcomes are consistent with previous studies in other
      domains which have shown reliable, although not conclusive, impairments in
      cognitive function, including memory, in patients with MDD, and highlight the
      role of olfactory identification and recognition tasks as an important additional
      tool to discriminate between patients characterised by different levels of
      severity of MDD.

PMID- 21940054
TI  - Neonatal androgenization affects the efficiency of beta-adrenoceptor-mediated
      modulation of thymopoiesis.
AB  - We tested the hypothesis that neonatal androgenization affects the efficacy of
      beta-adrenoceptor (beta-AR)-mediated fine tuning of thymopoiesis in adult female
      rats by modulating the thymic noradrenaline (NA) level and/or beta-AR expression.
      In adult rats administered with 1000 MUg testosterone enanthate at postnatal day
      2 a higher density of catecholamine (CA)-synthesizing thymic cells, including
      thymocytes, and a rise in their CA content was found. In addition, in these
      animals increased thymic noradrenergic nerve fiber fluorescence intensity,
      reflecting their increased CA content, was detected. These changes were followed
      by an increase in thymic NA concentration. The rise in thymic NA content in
      thymic nerve fibers and cells was associated with changes in the expression of
      mRNA for enzymes controlling pivotal steps in NA biosynthesis (tyrosine
      hydroxylase, dopamine-beta-hydroxylase) and inactivation (monoamine oxidase). In
      contrast, the thymic level of beta(2)-AR mRNA on a per cell basis and the
      receptor surface density on thymocytes was reduced in testosterone-treated (TT)
      rats. As a consequence, 14-day-long treatment with propranolol, a beta-AR
      blocker, was ineffective in modulating T-cell differentiation/maturation in TT
      rats. In conclusion, the study indicates the importance of the neonatal sex
      steroid milieu for shaping the immunomodulatory capacity of the thymic NA/beta-AR
      signaling system in adult rats.

PMID- 21940055
TI  - Reduction in IL-10 producing B cells (Breg) in multiple sclerosis is accompanied
      by a reduced naive/memory Breg ratio during a relapse but not in remission.
AB  - In this study, we assessed B cell subsets, including Bregs, during stable and
      active disease in relapsing remitting multiple sclerosis (RRMS) patients and
      related B cell subsets to vitamin D status. We report that RRMS patients have a
      decreased percentage of both memory B cells and Bregs compared to healthy
      controls. During a relapse, the reduction in Bregs involved in particular naive
      Bregs. We found no correlation between vitamin D status and B cell subsets. An
      effect of vitamin D on Bregs cannot be ruled out, since it might be the function
      that is interfered with instead of relative numbers.

PMID- 21940056
TI  - Upper respiratory colonization by Streptococcus pneumoniae in healthy pre-school
      children in south-east Poland.
AB  - OBJECTIVE: Carriage of Streptococcus pneumoniae in upper respiratory tract of
      healthy children is a major factor in the horizontal transmission of pneumococcal
      strains, especially between children attending day-care centers and may be also
      the source of infection in other individuals. During 8-month prospective study
      including 3 seasons (autumn, winter, spring), we determined risk factors for S.
      pneumoniae colonization in general and colonization at 2 or 3 time points in
      healthy pre-school children, including penicillin non-susceptible likewise
      multidrug resistant strains. METHODS: Pneumococcal cultures were obtained from
      311 children aged 3-5. Finally, a total of 342 isolates were identified.
      Resistance of pneumococcal isolates was determined and information about
      potential risk factors were obtained from questionnaires. RESULTS: A total of
      72.4% children were colonized by pneumococci at least once, including 8.4%
      children colonized at 3 time points, 25.4% children - twice and 38.6% children -
      only once. Penicillin non-susceptible pneumococcal colonization was found in
      36.3% children at least once while multidrug-resistant pneumococcal colonization
      in 34.1% children. Of the 10.9% and 10.6% children were colonized at 2 or 3 time
      points by penicillin non-sussceptible and multidrug-resistant isolates,
      respectively. Pneumococcal colonization (in general or by non-susceptible to
      penicillin isolates) was independently associated with day care attendance,
      having no siblings, frequent respiratory tract infections and higher number of
      antibiotic courses. Children attending day care center, with frequent respiratory
      tract infections, exposed to tobacco smoke were prone to colonization by
      multidrug-resistant isolates. Risk of colonization at 2 or 3 time points by
      pneumococcal isolates, including penicillin-nonsusceptible isolates, was
      associated with age and day care attendance while multidrug-resistant
      pneumococcal colonization was found to be significantly higher in children aged
      3, with frequent respiratory tract infections and higher number of antibiotic
      courses. CONCLUSION: These results indicate high rate of upper respiratory
      colonization by S. pneumoniae in healthy preschool children in Poland, including
      colonization by penicillin non-susceptible and multidrug-resistant pneumococci.

PMID- 21940057
TI  - Atrial fibrillation (AF) and cognitive impairment in the elderly: a case-control
      study.
AB  - AF is able not only to increase the risk of cognitive decline due to acute
      cerebrovascular events, but also to reduce cardiac output, with the consequence
      of impaired cerebral perfusion. The aim of this study was to evaluate the
      association between AF, dementia and depression in patients with negative
      anamnesis for past strokes. Our sample included 26 patients with a diagnosis of
      AF (paroxystic, persistent, permanent) and 31 patients with sinus rhythm,
      enrolled as controls. All selected patients underwent a Multidimensional
      Geriatric Assessment in order to investigate cognitive and behavioral functions.
      Statistical analysis of results showed a greater frequency of latent cognitive
      impairment in patients with AF, even in the absence of memory disorders. As a
      matter of facts, AF patients showed Mini Mental State Examination (MMSE) scores
      significantly lower than those with sinus rhythm (p<0.05) and Geriatric
      Depression Scale (GDS) scores higher than those without AF, evidencing a greater
      risk of depression too (p<0.02). Results showed a statistically significant
      association between AF, depression and cognitive impairment in early stage. In
      conclusion, AF is not only associated with the risk of developing cognitive
      impairment, but it can also be considered as a risk factor for dementia and
      depression, even in the absence of medical history of past stroke.

PMID- 21940058
TI  - Beneficial effects of intracoronary tirofiban bolus administration following
      upstream intravenous treatment in patients with ST-elevation myocardial
      infarction undergoing primary percutaneous coronary intervention: the ICT-AMI
      study.
AB  - BACKGROUND: We investigated whether an additional intracoronary tirofiban bolus
      administration following upstream intravenous treatment could further improve
      myocardial reperfusion and clinical outcome in patients with ST-elevation
      myocardial infarction (STEMI) undergoing primary percutaneous coronary
      intervention (PCI). METHODS: A total of 453 eligible STEMI patients were randomly
      allocated to intracoronary bolus administration of tirofiban (10 MUg/kg; n=229)
      or saline (10 mL; n=224) during primary PCI, followed by intravenous tirofiban
      infusion (0.15 MUg/kg/min) for 24-36 h. Serum levels of P-selectin, vWF, CD40L
      and serum amyloid A (SAA) in the coronary sinus were measured before and after
      intracoronary bolus administration. The primary endpoint was ST-segment
      resolution (STR) at 90 min after the procedure. Second endpoints included
      corrected TIMI frame count (cTFC), left ventricular volumes and ejection fraction
      (EF), and major adverse cardiac events (MACE) at 30-day and 6-month follow-up.
      RESULTS: Intracoronary tirofiban administration resulted in a higher rate of
      completed STR (59.0% vs. 44.6%, P=0.002), lower cTFC (21.6+/-5.4 vs. 23.7+/-7.8,
      P=0.048), and significantly reduced coronary sinus levels of P-selectin, vWF,
      CD40L and SAA. Patients treated with intracoronary tirofiban had a trend toward
      less MACE at 30 days (3.1% vs. 6.7%, P=0.072). At 6 months, left ventricular end
      systolic volume was smaller, EF was higher and MACE-free survival was improved
      (96.1% vs. 90.6%, P=0.020) in the intracoronary tirofiban group. CONCLUSIONS: An
      additional intracoronary tirofiban bolus administration following upstream
      intravenous treatment reduces coronary circulatory platelet activation and
      inflammatory process, and significantly improves myocardial reperfusion and left
      ventricular function as well as 6-month MACE-free survival for STEMI patients
      undergoing primary PCI.

PMID- 21940059
TI  - Evaluation of the relationship between personality traits, experience, education
      and biosecurity compliance on poultry farms in Quebec, Canada.
AB  - Biosecurity compliance is an issue in all types of animal production. Poor
      compliance is frequently related to lack of knowledge or comprehension. Human
      dimensions, such as personality and attitudes were also suggested as being
      related to compliance. As part of a larger study, personality traits, experience,
      education and training of employees, visitors and growers were evaluated to
      assess their relationship with their compliance with biosecurity measures when
      entering and exiting poultry barns. Biosecurity compliance was evaluated using
      hidden cameras. One hundred fourteen individuals involved in a total of 2379
      visits on 23 poultry farms responded to a personality test. Results demonstrated
      that several determinants of compliance exist, and some are related to
      personality, experience and education. Three personality traits were
      significantly associated with compliance: responsibility, complexity and action
      oriented. Such information has important implications for the selection of job
      applicants or task attribution and to enhance effectiveness of training programs.

PMID- 21940060
TI  - Investigation of Salmonella enterica in Sardinian slaughter pigs: prevalence,
      serotype and genotype characterization.
AB  - In order to improve the knowledge about the presence of Salmonella in pork meat
      in Sardinia (Italy), the prevalence and the sources of Salmonella at 5 pig
      slaughterhouses (slaughtered pigs and environment) were investigated and the
      isolates were characterised. A total of 462 samples were collected, 425 from pigs
      at slaughter and 41 from the slaughterhouse environment. Salmonella was isolated
      from 26/85 (30.5%) mesenteric lymph nodes, 14/85 (16.4%) colon contents, and from
      12/85 (14.1%) carcasses and livers. Salmonella prevalence was 38% (8/21) in
      samples from surfaces not in contact with meat, and 35% (7/20) in those from
      surfaces in contact with meat. Thirty-one pigs were identified as carriers of
      Salmonella in lymph nodes and/or colon content, but of these, only 8 carcasses
      were positive. A total of 103 Salmonella isolates were serotyped and genotyped.
      Eight different serotypes were detected; the most common were S. Derby (44/103,
      42.7%) and S. Typhimurium (24/103, 23.3%). The most prevalent S. Typhimurium
      phage type was DT193. Thirty-two isolates were found to be resistant to more than
      one antimicrobial (MDR). Pulse-field gel electrophoresis (PFGE) permitted the
      resolution of XbaI macrorestriction fragments of the Salmonella strains into 20
      distinct pulsotypes. Combined application of a plasmid profiling assay (PPA) and
      PFGE gave useful additional information to assist in tracing the routes of
      Salmonella contamination in abattoirs. To reduce Salmonella prevalence some
      preventive measures should be encouraged: the origin of infected slaughter
      animals should be identified and direct and cross-contamination of carcasses
      should be avoided by adhering to HACCP principles in association with good
      hygiene procedures (GHP).

PMID- 21940061
TI  - Caregiver reports of provider recommended frequency of blood glucose monitoring
      and actual testing frequency for youth with type 1 diabetes.
AB  - AIMS: To identify demographic, family and clinical characteristics associated
      with provider recommended frequency of blood glucose monitoring (BGM), actual
      frequency of BGM, and concordance between these categories in youth with type 1
      diabetes (T1D) as reported by child's caregiver. METHODS: Caregivers of 390
      children 10-17 years were interviewed about their children's providers'
      recommendations for frequency of BGM and their child's frequency of performance
      of BGM. RESULTS: The majority (92%) of caregivers reported being told that their
      child should BGM >=4 times per day and 78% reported their child checked that
      frequently. Caregivers of children who were younger, non-Hispanic White, from two
      parent households, higher income households, and on insulin pumps were more
      likely to report being told by their provider to perform BGM >=6 times per day
      and more likely to report that their child performed BGM >=6 times per day.
      Younger children and those with private health insurance were more likely to
      adhere to reported recommendations. Children whose caregivers reported that their
      child met/exceeded their provider recommendations had lower A1c values than those
      who did not. CONCLUSIONS: These findings may help clinicians identify subgroups
      of youth at-risk for poor diabetes management and provide further education in
      order to improve outcomes.

PMID- 21940063
TI  - Impact of variation in patient response on model-based control of glycaemia in
      critically ill patients.
AB  - Critically ill patients commonly experience stress-induced hyperglycaemia, and
      several studies have shown tight glycaemic control (TGC) can reduce patient
      mortality. However, tight control is often difficult to achieve due to
      conflicting drug therapies and evolving patient condition. Thus, a number of
      studies have failed to achieve consistently safe and effective TGC possibly due
      to the use of fixed insulin dosing protocols over adaptive patient-specific
      methods. Model-based targeted glucose control can adapt insulin and dextrose
      interventions to match identified patient insulin sensitivity. This study
      explores the impact on glycaemic control of assuming patient response to insulin
      is constant, as many protocols do, versus time-varying. Validated virtual trial
      simulations of glucose control were performed on adult and neonatal virtual
      patient cohorts. Results indicate assumptions of constant insulin sensitivity can
      lead to six-fold increases in incidence of hypoglycaemia, similar to literature
      reports and a commonly cited issue preventing increased adoption of TGC in
      critical care. It is clear that adaptive, patient-specific, approaches are better
      able to manage inter- and intra-patient variability than typical, fixed
      protocols.

PMID- 21940062
TI  - Epigenetic factors influencing resistance to nuclear reprogramming.
AB  - Patient-specific somatic cell reprogramming is likely to have a large impact on
      medicine by providing a source of cells for disease modelling and regenerative
      medicine. Several strategies can be used to reprogram cells, yet they are
      generally characterised by a low reprogramming efficiency, reflecting the
      remarkable stability of the differentiated state. Transcription factors,
      chromatin modifications, and noncoding RNAs can increase the efficiency of
      reprogramming. However, the success of nuclear reprogramming is limited by
      epigenetic mechanisms that stabilise the state of gene expression in somatic
      cells and thereby resist efficient reprogramming. We review here the factors that
      influence reprogramming efficiency, especially those that restrict the natural
      reprogramming mechanisms of eggs and oocytes. We see this as a step towards
      understanding the mechanisms by which nuclear reprogramming takes place.

PMID- 21940064
TI  - Prediction of a state of a subject on the basis of a stabilogram signal and video
      oculography test.
AB  - Postural stability decreases with ageing and may lead to accidental falls,
      isolation and a reduction in the quality of life. The age at the onset of
      postural derangement, its extent and the reason for deterioration are poorly
      known within an individual, but in general it becomes more severe with age. In
      order to prevent falls and avoid severe injuries the postural derangement has to
      be noticed by the person and the possible nursing personnel. In this work we
      propose such numerical features, which can discriminate the persons having good
      or poor postural stability. These features can also be utilized to measure the
      outcome and progression of balance training. With these postural stability
      algorithms providing stability features for a subject we managed to classify
      correctly the type of stance on the force platform in more than 80% of sixty
      subjects. We used k-nearest neighbor algorithm as an intuitive baseline method
      and compared its results with those of support vector machines and hidden Markov
      models.

PMID- 21940065
TI  - EMDS special issue: Systems biology of macrophages and dentritic cells in health
      and disease. Editorial.

PMID- 21940066
TI  - Expression of fur and its antisense alpha-fur from Microcystis aeruginosa PCC7806
      as response to light and oxidative stress.
AB  - Ferric uptake regulation (Fur) proteins are prokaryotic transcriptional
      regulators that integrate signaling of iron metabolism and oxidative stress
      responses with several environmental stresses. In photosynthetic organisms, Fur
      proteins regulate many genes involved in photosynthesis, nitrogen metabolism and
      other key processes. Also, Fur triggers the expression of virulence factors in
      many bacterial pathogens, and Fur from Microcystis aeruginosa has been shown to
      bind promoter regions of the microcystin synthesis gene cluster. In this work, we
      studied transcriptional responses of fur genes under different light intensities
      and oxidative stress. An antisense of fur, the alpha-fur RNA, plays an important
      role in regulating fur expression under oxidative stress, affecting levels of Fur
      protein in cells. Importantly, an active photosynthetic electron chain is
      required for the expression of the fur gene.

PMID- 21940067
TI  - Expression analysis of beta-glucosidase genes that regulate abscisic acid
      homeostasis during watermelon (Citrullus lanatus) development and under stress
      conditions.
AB  - The aim of this study was to obtain new insights into the mechanisms that
      regulate endogenous abscisic acid (ABA) levels by beta-glucosidase genes during
      the development of watermelons (Citrullus lanatus) and under drought stress
      conditions. In total, five cDNAs from watermelons were cloned by using reverse
      transcription-PCR (RT-PCR). They included three cDNAs (ClBG1, ClBG2 and ClBG3)
      homologous to those that encode beta-glucosidase l that hydrolyzes the ABA
      glucose ester (ABA-GE) to release active ABA, ClNCED4, which encodes 9-cis
      epoxycarotenoid dioxygenase (NCED), a key enzyme in ABA biosynthesis, and
      ClCYP707A1, encoding ABA 8'-hydroxylase. A BLAST homology search revealed that
      the sequences of cDNAs and the deduced amino acids of these genes showed a high
      degree of homology to comparable molecules of other plant species. During fruit
      development and ripening, the expressions of ClBG1, ClNCED4 and ClCYP707A1 were
      relatively low at an early stage, increased rapidly along with fruit ripening,
      and reached the highest levels at 27 days after full bloom (DAFB) at the harvest
      stage. This trend was consistent with the accumulation of ABA. The ClBG2 gene on
      the other hand was highly expressed at 5 DAFB, and then decreased gradually with
      fruit development. Unlike ClBG1 and ClBG2, the expression of ClBG3 was low at an
      early stage; its expression peak occurred at 15 DAFB and then declined to the
      lowest point. When watermelon seedlings were subjected to drought stress,
      expressions of ClBG1 and ClCYP707A1 were significantly down-regulated, while
      expressions of ClBG2 and ClNCED4 were up-regulated in the roots, stems and
      leaves. The expression of ClBG3 was down-regulated in root tissue, but was up
      regulated in stems and leaves. In conclusion, endogenous ABA content was
      modulated by a dynamic balance between biosynthesis and catabolism regulated by
      ClNCED4, ClCYP707A1 and ClBGs during development and under drought stress
      condition. It seems likely that beta-glucosidase genes are important for this
      regulation process.

PMID- 21940068
TI  - [Clinical characteristics, staging and treatment of patients with hepatocellular
      carcinoma in clinical practice. Prospective study of 136 patients].
AB  - Hepatocellular carcinoma (HCC) is the most frequent cause of mortality in
      patients with liver cirrhosis. There are no prospective series from a single
      tertiary hospital in Spain. MATERIAL AND METHODS: We performed a prospective
      study of patients with HCC in our center. Clinical and epidemiological
      characteristics, diagnostic method, staging according to the Barcelona Clinic
      Liver Cancer (BCLC) system and treatment were analyzed. RESULTS: A total of 136
      patients were included (80.9% men). The mean age was 66.62 +/- 11.68 years and
      91.2% were cirrhotic. Hepatitis C virus (HCV) was the leading cause of liver
      disease (38.97%). The suspected diagnosis was established by a surveillance
      program in 63.2%. Noninvasive American Association criteria for the Study of
      Liver Diseases (AASLD) were the main diagnostic method (73.5%). According to the
      BCLC, 58.1% were in the early stage (0-A), 21.3% in stage B, 12.5% in stage C and
      8.1% in stage D. Early stage patients had followed a surveillance program more
      frequently than those with non-early stages (79.75% versus 44.35%, p <0.001).
      Potentially curative initial treatment was used in 45.58%, the most common
      treatment being percutaneous ethanol injection (23.13%). CONCLUSIONS: Most
      patients with HCC in our hospital have cirrhosis, the most frequent cause being
      HCV. HCC surveillance in at-risk patients could increase diagnosis of HCC at an
      early stage. We achieved an early diagnosis in more than half of cases. The most
      common initial treatment was percutaneous therapy.

PMID- 21940069
TI  - [Vaccination of primary health care staff in the area of Ferrol (Galicia) against
      seasonal and swine flu].

PMID- 21940070
TI  - [Streptococcus agalactiae meningitis in an immunocompetent male].

PMID- 21940071
TI  - Synthesis and evaluation of the anti parasitic activity of aromatic nitro
      compounds.
AB  - A series of nitroaromatic compounds was synthesized and evaluated as potential
      antileishmanial and trypanocidal agents. Five compounds exerted significant anti
      leishmanial activity in vitro against promastigotes forms of Leishmania (L.)
      amazonensis, with IC(50) in the range of 23-59 MUmol L(-1), but none were active
      against amastigotes intracellular forms of Trypanosoma cruzi. In vitro
      cytotoxicity on the proliferation of human peripheral blood mononuclear cells
      (PBMC) stimulated with phytohemaglutinin (PHA) was also evaluated. Two compounds,
      6 and 7, were found to present a promising anti-leishmanial activity with IC(50)
      values of 59.5 and 50.6 MUM, respectively, without affecting the lymphocyte
      proliferation in PBMCs (selectivity index of 16.1 and 21.7, respectively),
      indicating low toxicity to human cells.

PMID- 21940072
TI  - Antimalarial activity of imidazo[2,1-a]isoindol-5-ol derivatives and related
      compounds.
AB  - The synthesis of several series of imidazo[2,1-a]isoindol-5-ol derivatives and
      the results of their evaluation against Plasmodium falciparum are presented and
      discussed. The effects of electron-withdrawing or-donating substituents on
      different parts of the molecule, as well as those produced by the incorporation
      of an additional fused ring, were analyzed. Several compounds showed significant
      antimalarial activity in vitro with IC(50) values as low as 60 nM and a certain
      efficacy in vivo by reducing parasitemia in Plasmodium berghei mouse models.

PMID- 21940073
TI  - Synthesis and characterization of novel
      bis(carboxylato)dichloridobis(ethylamine)platinum(IV) complexes with higher
      cytotoxicity than cisplatin.
AB  - A series of six novel bis(carboxylato)dichloridobis(ethylamine)platinum(IV)
      complexes was synthesized and characterized in detail by elemental analysis, FT
      IR, ESI-MS, HPLC, multinuclear ((1)H, (13)C, (15)N, (195)Pt) NMR spectroscopy and
      in one case by X-ray diffraction. Cytotoxic properties of the complexes were
      evaluated in four human tumor cell lines originating from ovarian carcinoma (CH1
      and SK-OV-3), colon carcinoma (SW480) and non-small cell lung cancer (A549) by
      means of the MTT colorimetrical assay. In addition, their octanol/water partition
      coefficients (log P values) were determined. Remarkably the most active (and also
      most lipophilic) compounds, having 4-propyloxy-4-oxobutanoato and 4-(2-propyloxy)
      4-oxobutanoato axial ligands, showed IC(50) values down to the low nanomolar
      range.

PMID- 21940074
TI  - [Gingival hypertrophy].

PMID- 21940075
TI  - [Lower limb oedema in a 53-year-old man].

PMID- 21940076
TI  - Kinetics of plutonium and americium sorption to natural clay.
AB  - Kinetics of Pu(IV) and Am(III) sorption from natural groundwater to three types
      of clays were studied at trace concentrations of the elements. Higher K(d) values
      were determined for sorption of Pu than of Am, and no clear dependence of the
      K(d) values and the kinetic coefficients on the composition of the clays can be
      deduced. Kinetic data evaluated by models for six different control processes
      indicated a sorption mechanism controlled by Pu or Am diffusion in the inert
      layer on the surface of the clays. Apart from the kinetics of the elements
      sorption, time-dependent changes in their bonding nature were also studied using
      a sequential extraction. It was found that Pu(IV) was predominantly associated
      with amorphous and crystalline Fe oxides as well as natural organic matter sites
      on the clays, whereas in the case of Am(III) the exchangeable and carbonate sites
      played the principal role.

PMID- 21940077
TI  - A synopsis of technical notes published in the British Journal of Oral and
      Maxillofacial Surgery in 2009/2010.
AB  - Technical notes form an important part of the British Journal of Oral and
      Maxillofacial Surgery (BJOMS). Many ideas are novel and some change practice.
      During 2009-2010, 39 technical notes were published in the journal, and they
      covered the whole remit of the specialty. In this article we briefly review and
      summarise these articles, and highlight the salient points.

PMID- 21940078
TI  - Cardiac output monitoring to guide fluid replacement in head and neck
      microvascular free flap surgery-what is current practice in the UK?
AB  - Appropriate fluid balance is an important factor in the survival of free flaps,
      and recently there has been a shift towards more conservative fluid regimens.
      Several surgical specialties have made extensive use of the relatively non
      invasive method of measuring cardiac output (CO) to optimise fluid balance during
      and after surgery, which has resulted in a shorter hospital stay, but little has
      been published in head and neck surgery. To ascertain its use in the head and
      neck we sent a postal questionnaire to the anaesthetic departments of 40 major
      head and neck units identified from the 2010 database of the British Association
      of Oral and Maxillofacial Surgeons (BAOMS). Questions were asked about the number
      of free flaps done in the unit each year, the monitoring of central venous and
      arterial blood pressure (and inotrope protocols), optimal target variables, and
      whether CO was monitored (with type of device). Thirty-two units responded (80%).
      While 26 units (81%) routinely monitored central venous pressure (CVP), CO was
      monitored in only 3 units (9%). There was a wide range of responses in relation
      to optimal variables and use of inotropes. As with other specialties, it is
      likely that CO monitoring will become widely used in head and neck reconstructive
      surgery. Not only does it enhance fluid optimisation, but it may also reduce
      hospital stay and morbidity. Appropriate clinical studies are urgently needed to
      evaluate its use in our specialty.

PMID- 21940079
TI  - Screening for alcohol and drug use in pregnancy.
AB  - OBJECTIVE: this study examined the clinical utility and precision of routine
      screening for alcohol and other drug use among women attending a public antenatal
      service. STUDY DESIGN: a survey of clients and audit of clinical charts.
      PARTICIPANTS AND SETTING: clients attending an antenatal clinic of a large
      tertiary hospital in Queensland, Australia, from October to December 2009.
      MEASUREMENTS AND FINDINGS: data were collected from two sources. First, 32 women
      who reported use of alcohol or other drugs during pregnancy at initial screening
      were then asked to complete a full substance use survey. Second, data were
      collected from charts of 349 new clients who attended the antenatal clinic during
      the study period. Both sensitivity (86%, 67%) and positive predictive value
      (100%, 92%) for alcohol and other drug use respectively, were high. Only 15% of
      surveyed women were uncomfortable about being screened for substance use in
      pregnancy, yet the chart audit revealed poor staff compliance. During the study
      period, 25% of clients were either not screened adequately or not at all. KEY
      CONCLUSIONS AND IMPLICATIONS FOR PRACTISE: despite recommended universal
      screening in pregnancy and the apparent acceptance by our participants, alcohol
      and other drug (A&OD) screening in the antenatal setting remains problematic.
      Investigation into the reasons behind, and ways to overcome, the low screening
      rate could improve health outcomes for mothers and children in this at-risk
      group. Targeted education and training for midwives may form part of the solution
      as these clinicians have a key role in implementing prevention and early
      intervention strategies.

PMID- 21940080
TI  - Women's experiences after an induced second trimester abortion.
AB  - OBJECTIVE: to describe women's experiences of an abortion in the second
      trimester. DESIGN: qualitative design using semi-structured interviews.
      SETTING/PARTICIPANTS: six women were interviewed after a second trimester
      abortion. METHODS: the women were interviewed in person after they were
      discharged from the hospital. Interviews were recorded, transcribed, and then
      analysed using qualitative content analysis. FINDINGS: four categories were
      identified: to consider and accept the decision; to lack understanding about the
      abortion procedure; to be in need of support and information; to have memories
      for life. Findings show that information and support during the whole abortion
      process is important. Women found it difficult to make the decision and going
      through abortion left memories for life. CONCLUSION: information and support is
      of great importance for women in this vulnerable situation. The need for further
      support points out the need to have follow-up contacts with women after an
      induced second trimester abortion.

PMID- 21940081
TI  - A novel intramedullary nail for micromotion stimulation of tibial fractures.
AB  - BACKGROUND: Animal studies and clinical trials have suggested that early
      application of controlled axial micromotion can accelerate healing of long bone
      fractures compared to rigid fixation. However, experimental investigations of
      micromotion constructs have been limited to external fixators, which have a
      higher incidence of complications than intramedullary nails. The purpose of this
      study was to assess whether a novel intramedullary nail design can generate
      stimulatory micromotion under minimal weight-bearing loads typical of the early
      healing period. METHODS: Eight cadaver tibiae were reamed, osteotomised, and
      implanted with commercially-available IM nails fitted with a custom insert that
      allowed 1mm of axial micromotion after proximal/distal interlocking. Specimens
      were mounted in a materials testing machine and subjected to cyclic axial loading
      while interfragmentary motion was measured using an extensometer. Implants were
      also tested in standard statically-locked mode. FINDINGS: The average force
      required to cause distraction of the fracture gap in micromotion mode was 37.0
      (SD 21.7) N. The mean construct stiffness was 1046.8 (SD 193.6) N/mm in static
      locking mode and 512.4 (SD 99.6) N/mm in micromotion mode (significantly
      different, P<0.001). INTERPRETATION: These results support the development of a
      micromotion-enabled IM nail because the forces required to cause interfragmentary
      movements are very low, less than the weight of the hanging shank and foot. In
      contrast to rigid-fixation nails, which require significant weight-bearing to
      induce interfragmentary motion, the micromotion-enabled nail may allow movement
      in non-weight-bearing patients during the early healing period when the benefits
      of mechanical stimulation are most critical.

PMID- 21940082
TI  - Resistance and vulnerability to stigmatization in abortion work.
AB  - The stigma surrounding abortion in the United States commonly permeates the
      experience of both those seeking this health service as well as those engaged in
      its provision. Annually there are approximately 1.2 million abortions performed
      in the United States; despite that existing research shows that abortion services
      are highly utilized, women rarely disclose their use of these services. In 2005
      only 1787 facilities that offer abortion services remained, a drop of almost 40
      percent since 1982 (Jones, Zolna, Henshaw, & Finer, 2008). While it has been
      acknowledged that all professionals working in abortion are labeled to some
      degree as different, no published research has explored stigmatization as a
      process experienced by the range of individuals that comprise the abortion
      providing workforce in the USA. Using qualitative data from a group of healthcare
      professionals doing abortion work in a Western state, this study begins to fill
      that gap, providing evidence of how the experience of stigma can vary and is
      managed within interactions in the workplace, in professional circles, among
      family and friends, and among strangers. The analysis shows that the experience
      of stigma for those providing abortion care is not a static or fixed loss of
      status. It is a dynamic situation in which those vulnerable to stigmatization can
      avoid, resist, or transform the stigma that would attach to them by varying
      degrees within selective contexts.

PMID- 21940083
TI  - How does network structure affect partnerships for promoting physical activity?
      Evidence from Brazil and Colombia.
AB  - The objective of this study was to describe the network structure and factors
      associated with collaboration in two networks that promote physical activity (PA)
      in Brazil and Colombia. Organizations that focus on studying and promoting PA in
      Brazil (35) and Colombia (53) were identified using a modified one-step
      reputational snowball sampling process. Participants completed an on-line survey
      between December 2008 and March 2009 for the Brazil network, and between April
      and June 2009 for the Colombia network. Network stochastic modeling was used to
      investigate the likelihood of reported inter-organizational collaboration. While
      structural features of networks were significant predictors of collaboration
      within each network, the coefficients and other network characteristics differed.
      Brazil's PA network was decentralized with a larger number of shared
      partnerships. Colombia's PA network was centralized and collaboration was
      influenced by perceived importance of peer organizations. On average,
      organizations in the PA network of Colombia reported facing more barriers (1.5
      vs. 2.5 barriers) for collaboration. Future studies should focus on how these
      different network structures affect the implementation and uptake of evidence
      based PA interventions.

PMID- 21940084
TI  - Life of a partnership: the process of collaboration between the National
      Tuberculosis Program and the hospitals in Yogyakarta, Indonesia.
AB  - Public-private partnerships (PPP) for improving the health of populations are
      currently attracting attention in many countries with limited resources. The
      Public-Private Mix for Tuberculosis Control is an example of an internationally
      supported PPP that aims to engage all providers, including hospitals, to
      implement standardized diagnosis and treatment. This paper explores mainly the
      local actors' views and experiences of the process of PPP in delivering TB care
      in hospitals in Yogyakarta Province, Indonesia. The study used a qualitative
      research design. By maximum variation sampling, 33 informants were purposefully
      selected. The informants were involved in the Public-Private Mix for Tuberculosis
      Control in Yogyakarta Province. Data were collected during 2008-2009 by in-depth
      interview and analyzed using content analysis techniques. Triangulation,
      reference group checking and peer debriefing were conducted to improve the
      trustworthiness of the data. This analysis showed that the process of partnership
      was dynamic. In the early phase of partnership, the National Tuberculosis Program
      and hospital actors perceived barriers to interaction such as low enthusiasm,
      lack of confidence, mistrust and inequality of relationships. The existence of an
      intermediary actor was important for approaching the National Tuberculosis
      Program and hospitals. After intensive interactions, compromises and acceptance
      were reached among the actors and even enabled the growth of mutual respect and
      feelings of programme ownership. However, the partnership faced declining
      interactions when faced with scarce resources and weak governance. The
      strategies, power and interactions between actors are important aspects of the
      process of collaboration. We conclude that good partnership governance is needed
      for the partnership to be effective and sustainable.

PMID- 21940085
TI  - The effect of national suicide prevention programs on suicide rates in 21 OECD
      nations.
AB  - Suicide has become a serious and growing public health problem in many countries.
      To address the problem of suicide, some countries have developed comprehensive
      suicide prevention programs as a collective political effort. However, no prior
      research has offered a systematic test of their effectiveness using cross
      national data. This paper evaluates whether the national suicide prevention
      programs in twenty-one OECD nations had the anticipated effect of reducing
      suicide rates. By analyzing data between 1980 and 2004 with a fixed-effect
      estimator, we test whether there is a statistically meaningful difference in the
      suicide rates before and after the implementation of national suicide prevention
      programs. Our panel data analysis shows that the overall suicide rates decreased
      after nationwide suicide prevention programs were introduced. These government
      led suicide prevention programs are most effective in preventing suicides among
      the elderly and young populations. By contrast, the suicide rates of working-age
      groups, regardless of gender, do not seem to respond to the introduction of
      national prevention programs. Our findings suggest that the presence of a
      national strategy can be effective in reducing suicide rates.

PMID- 21940086
TI  - Dying cases in emergency places: caring for the dying in emergency departments.
AB  - In an ageing society, like the UK, where long-term illness dominates healthcare,
      there has been a change in the way that the end-of-life is approached and
      experienced. Advancing technology, inadequate knowledge and inconsistency in
      palliative care services have complicated the ability to recognise imminent dying
      and many people access emergency services at the end-of-life. Drawing on
      ethnographic research exploring end-of-life care in one large Emergency
      Department (ED), the authors examine the spaces of dying and death, which are
      created in a place designed to save life, and not necessarily to provide
      supportive and palliative care. Despite the high need for attention in an
      emergency crisis, this study shows that the approach taken to care for someone at
      the end-of-life, and consequently the space in which they are cared for, often
      falls short of the expectations of the dying patient and their relatives. It is
      argued that the dying body is seen as dirty and polluted in the sterile,
      controlled, clinical environment and is therefore 'matter out of place'. Attempts
      are made to conceal or remove the dying patient, the bereaved relatives and the
      deceased body protecting the natural order of the ED. Consequently, the
      individual supportive and palliative care needs of the dying are often
      overlooked. This paper highlights the needs of patients as death nears in the ED
      and argues that the critical decisions made in the ED have a significant impact
      on the quality of care experienced by patients, who spend the last few hours of
      their life there.

PMID- 21940087
TI  - Predictors for tumor recurrence after primary definitive surgery for oral cancer.
AB  - PURPOSE: The purpose of this study was to identify significant predictors for
      oral squamous cell carcinoma recurrence. PATIENTS AND METHODS: This Ambispective
      cohort study was performed in consecutive metastasis-free patients treated for
      oral squamous cell carcinoma with curative intent from 1998 through 2003.
      Variables included gender, age, tumor site, macroscopic pattern of the lesion,
      coexisting disorders (diabetes, hepatic and heart disorders, other
      tumors/diseases), degree of differentiation, and pathologic TNM stage. Tumor
      recurrence was considered the dependent variable (outcome). The distribution of
      recurrences was assessed with chi(2) test. Survival times were estimated by
      Kaplan-Meier curves and differences were examined with log-rank test. Multiple
      Cox regression study was also performed. The significance level chosen for all
      tests was P < .05. RESULTS: One hundred eighteen patients entered the study.
      Tumor recurrence was 44.9% during the follow-up period (10% local, 29.7%
      regional, and 5% distant). The mean period that had elapsed before recurrence was
      15 months (1.5 to 81.8), with most recurrences (66%) during the first year after
      treatment (84.9% before 2 years). Multivariate Cox regression analysis indicated
      the presence of a coexisting disorder (P = .022) as the most relevant prognostic
      factor for relapse, because patients with associated diseases had a 2.43-fold
      risk of recurrence. Tumor stage (P = .037), degree of differentiation (P = .042),
      and macroscopic pattern of the lesion (P = .022) were also identified as
      prognostic factors for relapse. CONCLUSIONS: The risk profile for oral cancer
      recurrence includes patients younger than 60 years with coexisting diseases whose
      primary tumor occurred as an ulcerated lesion, and diagnosed at an advanced stage
      with a poorly differentiated tumor.

PMID- 21940088
TI  - Renal cell carcinoma presenting as a tongue lesion.

PMID- 21940089
TI  - The use of a simplified nasal stent in infants with complete unilateral cleft lip
      and palate.

PMID- 21940090
TI  - An evaluation of patients' knowledge about perioperative information for third
      molar removal.
AB  - PURPOSE: Third molar removal is usually accompanied by a high degree of patient
      anxiety. Lack of knowledge about the procedure is a major contributor to this
      anxiety. The aim of this study was to investigate the perioperative perceptions
      of patients who underwent extraction of third molars to assess their concerns
      during the surgical experience. MATERIALS AND METHODS: Issues related to
      preoperative, intraoperative, and postoperative phases of the experience were
      assessed with the purpose of identifying the most frequent questions and
      misconceptions. Data were assessed to correlate the influence of previous
      experience with extraction(s) with the appropriate knowledge of third molar
      surgery, as well as knowledge variations as to the age and gender of the
      patients. RESULTS: The sample was composed of 67 patients (43 female patients and
      24 male patients) divided into 2 groups: The first had some previous experience
      with extractions (25 patients), and the second had no experience (42 patients).
      The most frequent questions regarded the number of teeth to be extracted (65.4%),
      and the most prevalent misconception was about medications before surgery
      (28.4%). Patients with a previous history of dental extractions had more
      questions about use of medication before surgery (P = .03). Patients without
      previous experience with extraction had more concerns about anesthesia techniques
      (P = .02) or the number of teeth that would be removed during the same procedure
      (P = .02). Other questions and misconceptions were not different between these
      groups. CONCLUSIONS: Patients with a history of tooth extraction and those
      without it presented different patterns of knowledge about third molar surgery.
      Both groups of patients needed detailed perioperative instructions about the
      procedure. These results may provide oral and maxillofacial surgeons with useful
      information about patients' knowledge throughout the surgical process.

PMID- 21940091
TI  - Is clonidine an adequate alternative to epinephrine as a vasoconstrictor in
      patients with hypertension?
AB  - PURPOSE: To evaluate the safety and efficacy of an admixture of lidocaine with
      clonidine with regard to the anesthetic abilities, hemodynamic parameters, and
      postoperative pain control and to compare the results with those obtained with a
      lidocaine-epinephrine solution. MATERIALS AND METHODS: A total of 50 patients
      with poorly controlled, moderate hypertension (American Society of
      Anesthesiologists class II) who presented for uncomplicated upper third molar
      extraction were included in a double-blind study. The time of onset of action,
      duration, and intensity of anesthesia and the vasoconstrictor properties were
      evaluated. The hemodynamic changes (ie, systolic blood pressure, diastolic blood
      pressure, mean arterial pressure, heart rate, ST-segment depression of 1 mm or
      greater, and cardiac arrhythmias) were recorded. The presence of postoperative
      pain and analgesic requirements were also compared. The results were analyzed
      using an unpaired, type sample equal-variance t test with the Bonferroni
      correction. RESULTS: Of the 50 patients with hypertension (American Society of
      Anesthesiologists class II), 25 received 2 mL of 2% lidocaine with clonidine (15
      MUg/mL) and 25 received lidocaine with epinephrine (12.5 MUg/mL). There were no
      significant differences between the 2 agents with regard to the time of onset of
      action, duration or intensity of anesthesia, or the vasoconstrictor properties.
      The clonidine group showed better hemodynamic parameters compared with the
      epinephrine group. The clonidine group showed significantly lesser postoperative
      pain and, therefore, had lesser analgesic consumption. CONCLUSIONS: Clonidine
      could be a useful and safe alternative to epinephrine for intraoral block
      anesthesia with lidocaine in patients with hypertension and American Society of
      Anesthesiologists class II.

PMID- 21940092
TI  - Human intraoral harvested mesenchymal stem cells: characterization, multilineage
      differentiation analysis, and 3-dimensional migration of natural bone mineral and
      tricalcium phosphate scaffolds.
AB  - PURPOSE: The aim of this study was the establishment of a minimally invasive
      technique of mesenchymal stem cell (MSC) harvesting and a predictable isolation
      and cultivation method on 2 different bone substitutes used as potential
      scaffolds. MATERIALS AND METHODS: Human MSCs isolated from the posterior maxilla
      were characterized by flow cytometric analysis. After in vitro expansion, cells
      were cultured and differentiated toward osteogenic, adipogenic, and chondrogenic
      lineages in 2-dimensional cultures and on natural bone mineral of bovine origin
      and beta-tricalcium phosphate scaffolds. Three-dimensional growth was analyzed
      using live cell staining and confocal laser scanning microscopy. RESULTS: MSCs
      from all patients demonstrated the same immunophenotype, with expression of CD73,
      CD90, and CD105 but no expression of CD45, CD34, CD14, CD11, and HLA-DR. The
      potential of MSCs for multilineage differentiation along osteogenic, adipogenic,
      and chondrogenic lines was shown. Based on knowledge of the characteristics of
      the cells, a method was established to increase MSC expansion efficiency and
      seeding conditions on each scaffold. Results of the in vitro characterization and
      laser scanning microscopy visualized the 3-dimensional growth of MSCs on the 2
      scaffold types. CONCLUSIONS: The present data showed that intraoral MSCs can be
      cultured predictably under 2- and 3-dimensional conditions, have proved multiple
      potencies, and thus seem to be potential candidates for tissue engineering
      approaches in maxillofacial reconstructions.

PMID- 21940093
TI  - Magnitude and chronometry of neural mechanisms of emotion regulation in subtypes
      of aggressive children.
AB  - Emotion regulation is a key social skill and children who fail to master it are
      at risk for clinical disorders. Specific styles of emotion regulation have been
      associated with particular patterns of prefrontal activation. We investigated
      whether anxious aggressive children would reveal a different pattern of cortical
      activation than non-anxious aggressive children and normally-developing children.
      We examined the magnitude and timing of source activation underlying the N2-an
      ERP associated with inhibitory control-during a go/nogo task with a negative
      emotion induction component (loss of earned points). We estimated cortical
      activation for two regions of interest-a ventral prefrontal and a dorsomedial
      prefrontal region-for three 100-ms windows over the range of the N2 (200-500 ms).
      Anxious aggressive children showed high ventral prefrontal activation in the
      early window; non-anxious aggressive children showed high ventral prefrontal
      activation in the late window, but only for the duration of the emotion
      induction; and normally-developing children showed low ventral prefrontal
      activation throughout. There were no group differences in dorsomedial prefrontal
      activation. These results suggest that anxious aggressive children recruit
      ventral prefrontal activation quickly and indiscriminately, possibly giving rise
      to their rigid, threat-oriented approach to conflict. The late ventral prefrontal
      activation seen for non-anxious aggressive children may underlie a more delayed,
      situation-specific, but ineffective response to frustration.

PMID- 21940094
TI  - Clinical value of morphine, pholcodine and poppy seed IgE assays in drug-abusers
      and allergic people.
AB  - BACKGROUND: The diagnosis of anaphylactic reactions due to opiates during
      anaesthesia can be difficult, since in most cases various drugs may have been
      administered. Detection of specific IgE to poppy seed might be a marker for
      sensitisation to opiates in allergic people and heroin-abusers. This study
      assessed the clinical value of morphine, pholcodine and poppy seed skin-prick and
      IgE determination in people suffering hypersensitivity reactions during
      anaesthesia or analgesia and drug-abusers with allergic symptoms. METHODS: We
      selected heroin abusers and patients who suffered severe reactions during
      anaesthesia and analgesia from a database of 23,873 patients. The diagnostic
      yield (sensitivity, specificity and predictive value) of prick and IgE tests in
      determining opiate allergy was analysed. RESULTS: Overall, 149 patients and 200
      controls, mean age 32.9 +/- 14.7 years, were included. All patients with positive
      prick to opiates showed positive prick and IgE to poppy seeds, but not to
      morphine or pholcodine IgE. Among drug-abusers, 13/42 patients (31%) presented
      opium hypersensitivity confirmed by challenge tests. Among non-drug abusers,
      sensitisation to opiates was higher in people allergic to tobacco (25%), P<.001.
      Prick tests and IgE against poppy seed had a good sensitivity (95.6% and 82.6%,
      respectively) and specificity (98.5% and 100%, respectively) in the diagnosis of
      opiate allergy. CONCLUSIONS: Opiates may be significant allergens. Drug-abusers
      and people sensitised to tobacco are at risk. Both the prick and specific IgE
      tests efficiently detected sensitisation to opiates. The highest levels were
      related to more-severe clinical profiles.

PMID- 21940095
TI  - Trends in future N2O emissions due to land use change.
AB  - Better insight in the possible range of future N2O emissions can help to
      construct mitigation and adaptation strategies and to adapt land use planning and
      management to climate objectives. The Dutch fen meadow landscape is a hotspot of
      N2O emission due to high nitrogen inputs combined with moist peat soils due to
      land use change. Socio-economic developments in the area are expected to have
      major impacts on N2O emission. The goals of this study are to estimate changes in
      N2O emissions for the period 2006-2040 under three different scenarios for the
      Dutch fen meadow landscape (rural production, rural fragmentation, and rural
      multifunctionality) and to quantify the share of different emission sources.
      Three scenarios were constructed and quantified based on the Story-And-Simulation
      approach. The rural production and the rural fragmentation scenarios are
      characterized by globalization and a market-oriented economy; in the rural
      production scenario dairy farming has a strong competitive position in the study
      region, while under the rural fragmentation scenario agriculture is declining.
      Under the rural multifunctionality scenario, the global context is characterized
      by regionalization and stronger regulation toward environmental issues. The N2O
      emission decreased between 2006 and 2040 under all scenarios. Under the rural
      production scenario, the N2O emission decreased by 7%. Due to measures to limit
      peat mineralization and policies to reduce agricultural emissions, the rural
      multifunctionality scenario showed the largest decrease in N2O emissions (44%).
      Under the rural fragmentation scenario, in which the dairy farming sector is
      diminished, the emission decreased by 33%. Compared to other uncertainties
      involved in N2O emission estimates, the uncertainty due to possible future land
      use change is relatively large and assuming a constant emission with time is
      therefore not appropriate.

PMID- 21940096
TI  - Lymph node dissection in renal cell carcinoma.
AB  - CONTEXT: Although lymphadenectomy (lymph node dissection [LND]) is currently
      accepted as the most accurate and reliable staging procedure for the detection of
      lymph node invasion (LNI), its therapeutic benefit in renal cell carcinoma (RCC)
      still remains controversial. OBJECTIVE: Review the available literature
      concerning the role of LND in RCC staging and outcome. EVIDENCE ACQUISITION: A
      Medline search was conducted to identify original articles, review articles, and
      editorials addressing the role of LND in RCC. Keywords included kidney neoplasms,
      renal cell cancer, renal cell carcinoma, kidney cancer, lymphadenectomy, lymph
      node excision, lymphatic metastases, nephrectomy, imaging, and complications. The
      articles with the highest level of evidence were identified with the consensus of
      all of the collaborative authors and were critically reviewed. This review is the
      result of an interactive peer-reviewing process by an expert panel of co-authors.
      EVIDENCE SYNTHESIS: Renal lymphatic drainage is unpredictable. The newer
      available imaging techniques are still immature in detecting small lymph node
      metastases. Results from the European Organization for Research and Treatment of
      Cancer trial 30881 showed no benefit in performing LND during surgery for
      clinically node-negative RCC, but the results are limited to patients with the
      lowest risk of developing LNI. Numerous retrospective series support the
      hypothesis that LND may be beneficial in high-risk patients (clinical T3-T4, high
      Fuhrman grade, presence of sarcomatoid features, or coagulative tumor necrosis).
      If enlarged nodes are evident at imaging or palpable during surgery, LND seems
      justified at any stage. However, the extent of the LND remains a matter of
      controversy. CONCLUSIONS: To date, the available evidence suggests that an
      extended LND may be beneficial when technically feasible in patients with locally
      advanced disease (T3-T4) and/or unfavorable clinical and pathologic
      characteristics (high Fuhrman grade, larger tumors, presence of sarcomatoid
      features, and/or coagulative tumor necrosis). Although node-positive patients
      often harbor distant metastases as well, the majority of retrospective
      nonrandomized trials seem to suggest a possible benefit of regional LND even for
      this group of patients. In patients with T1-T2, clinically negative lymph nodes
      and absence of unfavorable clinical and pathologic characteristics, regional LND
      offers limited staging information and no benefit in terms of decreasing disease
      recurrence or improving survival.

PMID- 21940097
TI  - Hormone therapy for prostate cancer: what have we done with Charles Huggins'
      legacy?

PMID- 21940099
TI  - Validation of preoperative nomograms predicting lymph node involvement in
      prostate cancer: a Bi-institutional study.

PMID- 21940100
TI  - Preparation of ceramic-corrosion-cell fillers and application for cyclohexanone
      industry wastewater treatment in electrobath reactor.
AB  - As new media, ceramic-corrosion-cell fillers (Cathode Ceramic-corrosion-cell
      Fillers - CCF, and Anode Ceramic-corrosion-cell Fillers - ACF) employed in
      electrobath were investigated for cyclohexanone industry wastewater treatment.
      60.0 wt% of dried sewage sludge and 40.0 wt% of clay, 40.0 wt% of scrap iron and
      60.0 wt% of clay were utilized as raw materials for the preparation of raw CCF
      and ACF, respectively. The raw CCF and ACF were respectively sintered at 400
      degrees C for 20 min in anoxic conditions. The physical properties (bulk density,
      grain density and water absorption), structural and morphological characters and
      toxic metal leaching contents were tested. The influences of pH, hydraulic
      retention time (HRT) and the media height on removal of COD(Cr) and cyclohexanone
      were studied. The results showed that the bulk density and grain density of CCF
      and ACF were 869.0 kg m(-3) and 936.3 kg m(-3), 1245.0 kg m(-3) and 1420.0 kg m(
      3), respectively. The contents of toxic metal (Cu, Zn, Cd, Pb, Cr, Ba, Ni and As)
      were all below the detection limit. When pH of 3-4, HRT of 6h and the media
      height of 60 cm were applied, about 90% of COD(cr) and cyclohexanone were
      removed.

PMID- 21940101
TI  - Enhanced degradation of p-nitrophenol in soil in a pulsed discharge plasma
      catalytic system.
AB  - A pulsed discharge plasma-TiO(2) catalytic (PDPTC) system was developed to
      investigate the degradation of p-nitrophenol (PNP) in soil. The effects of TiO(2)
      amount, soil pH and air moisture on PNP degradation were evaluated, and PNP
      degradation processes were predicted with Gaussian 03W combined with density
      functional theory (DFT). Experimental results showed that 88.8% of PNP could be
      smoothly removed in 10 min in the PDPTC system with the specific energy density
      of 694 J g(soil)(-1), compared with 78.1% in plasma alone system. The optimum
      TiO(2) amount was 2% in the present study, and higher TiO(2) amount exhibited an
      inhibitive effect. Alkaline soil was favorable for PNP removal. The increase of
      air moisture to a certain extent could enhance PNP removal. A DFT calculation
      presented that there was a high preference for the -ortho and -para positions
      with respect to the functional -OH group of PNP molecule for OH radicals attack.
      The main intermediates were hydroquinone, benzoquinone, catechol, phenol,
      benzo[d][1,2,3]trioxole, acetic acid, formic acid, NO(2)(-), NO(3)(-) and oxalic
      acid. The generation of hydroxylated intermediates, NO(2)(-) and NO(3)(-)
      suggested that the experimental results were consistent with those of the
      theoretical prediction.

PMID- 21940102
TI  - Photocatalytic production of 1O2 and *OH mediated by silver oxidation during the
      photoinactivation of Escherichia coli with TiO2.
AB  - Ag loaded TiO(2) was applied in the photocatalytic inactivation of Escherichia
      coli under ultraviolet (UV) and visible (Vis) light irradiations. Ag enhanced the
      TiO(2) photodisinfecting effect under Vis irradiation promoting the formation of
      singlet oxygen and hydroxyl radicals as identified by EPR analyses. Ag
      nanoparticles, determined on TEM analyses, undergo an oxidation process on the
      TiO(2)'s surface under UV or Vis irradiation as observed by XPS. In particular,
      UV pre-irradiation of the material totally diminished its photodisinfection
      activity under a subsequent Vis irradiation test. Under UV, photodegradation of
      dichloroacetic acid (DCA), attributed to photoproduced holes in TiO(2), was
      inhibited by the presence of Ag suggesting that oxidation of Ag(0) to Ag(+) and
      Ag(2+) is faster than the oxidative path of the TiO(2)'s holes on DCA molecules.
      Furthermore, photoassisted increased of Ag(+) concentration on TiO(2)'s surface
      enhances the bacteriostatic activity of the material in dark periods. Indeed,
      this latter dark contact of Ag(+)-TiO(2) and E. coli seems to induce recovering
      of the Vis light photoactivity promoted by the surface Ag photoactive species.

PMID- 21940103
TI  - The initial discovery of thorny-headed worms in sheep.
AB  - Acanthocephalans belonging to the species Acanthocephalus lucii were found in the
      colon of a lamb from ecological farms in the Czech Republic. The main
      determination features used for these acanthocephalans are the shape and size of
      the hooks as well as the number of hooks on the proboscis. Three immature
      specimens measured 5.0-13.2mm in length; the appearance of the acanthocephalan
      body (in the studied material) suggests that passage through this unusual host
      causes the cystacanths to slightly increase in length. In the case of the lambs
      examined, the infection may be acquired through the accidental ingestion of the
      intermediate host - waterlouse (Asellus aquaticus).

PMID- 21940104
TI  - Prognostic scoring systems in burns: a review.
AB  - Survival after burn has steadily improved over the last few decades. Patient
      mortality is, however, still the primary outcome measure for burn care. Scoring
      systems aim to use the most predictive premorbid and injury factors to yield an
      expected likelihood of death for a given patient. Age, burn surface area and
      inhalational injury remain the mainstays of burn prognostication, but their
      relative weighting varies between scoring systems. Biochemical markers may hold
      the key to predicting outcomes in burns. Alternatively, the incorporation of
      global scales such as those used in the general intensive care unit may have
      relevance in burn patients. Outcomes other than mortality are increasingly
      relevant, especially as mortality after burns continues to improve. The evolution
      of prognostic scoring in burns is reviewed with specific reference to the more
      widely regarded measures. Alternative approaches to burn prognostication are
      reviewed along with evidence for the use of outcomes other than mortality. The
      purpose and utility of prognostic scoring in general is discussed with relevance
      to its potential uses in audit, research and at the bedside.

PMID- 21940105
TI  - Estimating reaction delay for glucose level prediction.
AB  - The pancreas, liver and hypothalamus have a regulatory function in the glucose
      homeostasis. As the blood glucose level changes, these compartments react and the
      level changes again. Subsequently to this reaction, the interstitial glucose
      level changes with some delay. In this paper, I propose a hypothesis that the
      change of the blood glucose level includes information about the estimated rate
      with which the hypothalamus expects the blood glucose level to return to normal
      range, by means of regulatory mechanisms of glucose homeostasis. As the
      interstitial glucose level change reflects the blood glucose level change, I
      propose a method to estimate the blood-to-interstitial glucose level delay. It is
      an important factor for glucose level prediction. Once the delay was calculated,
      it was possible to relate the present blood glucose level and future interstitial
      glucose level with such coefficients, which do not seem to change over the time
      of the experiment to a significant extent. Perhaps, it is a parameterization of
      regulatory processes of glucose homeostasis, which could be possibly encoded
      within hypothalamus set-points. The delays were constant per subject and ranged
      from 7 min up to 34 min for hereditary hypertriglyceridemic rats of 230-480 g
      weight, in experiments with a variable glucose infusion rate.

PMID- 21940106
TI  - Clinical value of duodenal biopsies--beyond the diagnosis of coeliac disease.
AB  - At upper gastrointestinal endoscopy to investigate unexplained diarrhea and iron
      deficiency anemia, duodenal biopsies are often taken to exclude a diagnosis of
      coeliac disease. While histology remains the gold standard for this diagnosis,
      recent developments in serological testing may overtake this as a first line test
      and biopsy restricted to confirming the diagnosis. Established coeliac disease on
      biopsy is straightforward, but early lesions may pose a challenge. Newer
      endoscopic procedures such as push-pull enteroscopy (balloon enteroscopy) with
      biopsy allow access to the small bowel beyond the second part of the duodenum.
      Controversy remains as to what constitutes the normal histology of the duodenum,
      and small bowel. Lymphocytic duodenosis (increased intraepithelial lymphocytes
      with normal villous architecture) in patients with negative coeliac serology can
      be associated with Helicobacter pylori, drugs, autoimmune and other diseases
      including food allergy. Full thickness small intestinal biopsies can aid in
      investigation of enteric neuropathies in severe dysmotility disorders. Biopsies
      are also taken to investigate malabsorption due to suspected infectious and
      metabolic disorders. Despite highly active anti-retroviral therapy (HAART),
      immunosuppressed patients may be affected by duodenal pathogens. The histology of
      duodenal mucosa in acid related disorders reflects the damage seen at endoscopy.
      Although the prevalence of duodenal ulcer disease is decreasing, drugs causing
      ulceration remain an important disease entity. Recent observations in functional
      bowel disorders suggest that the duodenum may be a key site for pathology. In
      functional dyspepsia, patients with early satiety may have excess eosinophil
      infiltration, and the mast cell is probably a key player in the irritable
      syndrome in the small intestine.

PMID- 21940107
TI  - Ploidy and S-phase fraction as predictive markers of response to radiotherapy in
      cervical cancer.
AB  - The aim of this study was to investigate the potential clinical utility of DNA
      flow cytometry biomarkers, ploidy, and S-phase fraction (SPF) in predicting
      overall survival in cervical cancer. This prospective study involved 159 patients
      with cervical carcinoma (median follow-up, 48 months). Pretreatment clinical
      staging was done according to the FIGO 2009 update classification. Biopsy tumor
      samples were used for flow cytometry analysis and histological examination. A
      prognostic study was performed using both Cox and Bayesian Weibull regression
      models. Eighty (50.3%) tumors presented DNA aneuploidy, mostly observed in
      adenosquamous (AS) cell carcinoma (8 of 9 cases) and adenocarcinoma (AC) (12 of
      17 cases). The median SPF value (8.6%) was used for discriminating low vs. high
      tumor cell proliferation. High SPF significantly correlated with aneuploidy
      (p<0.001). All AS carcinomas had SPF>15%, while all ACs presented SPF<10%
      (p<0.001). Forty-three (27%) patients died of the disease during follow-up. Log
      rank tests revealed significant differences between survival curves for older
      patients (>=44 years) (p=0.029), advanced clinical staging (p<0.001), and DNA
      diploidy in stage IIB of disease (p=0.039). Both regression analyses showed that
      advanced clinical staging and low SPF independently predict worse overall
      survival of patients. The results suggest that DNA flow cytometry parameters can
      provide additional predictive information in cervical cancer management.

PMID- 21940108
TI  - Oncogenic anaplastic lymphoma kinase (ALK) mutation in neuroblastomas and other
      pediatric tumors.
AB  - Neuroblastoma (NB) is one of the most common malignant pediatric tumors that show
      aggressive behavior. Most advanced-stage NBs have proven refractory to many
      treatment modalities, and a fundamental alternative therapy, such as inhibition
      of biological pathways, is now being explored. Anaplastic lymphoma kinase (ALK)
      has recently been identified as an activation mutation in familial or high-risk
      sporadic NBs. We examined the prevalence of the ALK mutation in 54 NB cases (23
      pre-treatment cases and 31 cases for which specimens were available before and
      after treatment) and the presence of the ALK mutation in various pediatric
      tumors. We detected the ALK mutation (F1174C and R1275Q) in 2 (3.7%) of the 54 NB
      specimens. Both cases showed poorly differentiated and advanced-stage NBs. No ALK
      mutations were detected in other pediatric tumors. The frequency of the ALK
      mutation was somewhat lower than that expected in Korean patients with NBs. The
      mutation detected in the present study was one of the hotspot mutations,
      including positions of F1174 and R1275 reported previously. The results of the
      present study suggest the possibility of potential roles of ALK inhibitors in the
      therapeutics of a small population of neuroblastoma carrying mutated ALK kinases.

PMID- 21940109
TI  - ETS-1 proto-oncogene as a key newcomer molecule to predict invasiveness in
      laryngeal carcinoma.
AB  - ETS-1 protein is one of the key regulators in tumor invasion and progression. We
      aimed to evaluate the role of ETS-1 in the invasiveness and progression of
      laryngeal squamous carcinoma, as well as to determine the correlations between
      clinicopathological characteristics and expression of this molecule. We assessed
      the levels of ETS-1 in a total of 96 laryngeal specimens of varying degrees of
      dysplasia, microinvasive squamous carcinoma (8), and invasive squamous carcinoma
      (60), using normal mucosal epithelium (10) as a positive control. The
      relationship between ETS-1 expression and clinicopathological parameters of
      laryngeal carcinoma was also analyzed. We found a significantly higher ETS-1
      expression in invasive laryngeal squamous cell carcinomas than in dysplasia
      (P<0.001). A correlation between ETS-1 expression scores and grade was detected -
      T factor, stage, cartilage invasion, lymph node metastasis, as well as depth of
      invasion in laryngeal tumors. Our study is the first to demonstrate that ETS-1
      expression is significantly increased in invasive carcinoma, but it is absent in
      low-moderate grade laryngeal dysplasia and non-neoplastic laryngeal mucosa. This
      data suggest that ETS-1 expression may play an important role in tumor invasion,
      and may function in the initiation of the invasive process in laryngeal squamous
      cell carcinoma.

PMID- 21940110
TI  - Somatic mutations of caspase-2 gene in gastric and colorectal cancers.
AB  - There is mounting evidence that evasion of apoptosis is a hallmark of cancer.
      Caspase-2, which plays roles in both extrinsic and intrinsic apoptosis pathways,
      is considered a candidate tumor suppressor. The aim of this study was to explore
      the possibility that genetic alterations of caspase-2 gene are present in human
      cancers. In this study, we analyzed the entire coding sequences of human caspase
      2 gene for the detection of somatic point mutations in 90 gastric carcinomas and
      100 colorectal carcinomas by polymerase chain reaction (PCR)-single strand
      conformation polymorphism (SSCP). Of the cancers analyzed, two gastric cancers
      (2/90; 2.2%) and two colorectal cancers (2/100; 2.0%) harbored somatic missense
      mutations of caspase-2. The mutations consisted of p.V46M (at prodomain), p.S157L
      (at prodomain), p.R357K (at p13 subunit), and p.R397L (at p13 subunit). We
      expressed these tumor-derived mutants in 293 T cells and found that three of the
      mutants decreased cell death activity of caspase-2. Our data indicate that
      somatic mutation of caspase-2 is rare in gastric and colorectal carcinomas.
      However, functional data of the caspase-2 mutations also suggest that caspase-2
      gene mutation might affect the pathogenesis of some gastric and colorectal
      cancers by inactivating cell death function of caspase-2.

PMID- 21940111
TI  - Stratifin expression is a novel prognostic factor in human gliomas.
AB  - Stratifin (14-3-3sigma or SFN) is a member of the 14-3-3 family of proteins which
      play critical roles in different cellular signaling processes. Stratifin as a
      potential tumor suppressor gene plays an important role in carcinogenesis and
      metastasis. The aim of this study was to investigate the expression of Stratifin
      in human gliomas and to analyze its expression profile with respect to tumor
      development. The expression pattern of Stratifin was analyzed by
      immunohistochemistry and/or Western blotting in tumor samples from 186 patients
      with different grades of gliomas. Prognostic significance was assessed using
      Kaplan-Meier survival estimates and Cox regression analyses. The expression
      pattern of Stratifin was correlated with the pathological and clinical
      characteristics of the patients with gliomas. Western blot analysis indicated
      that the average optical densitometry (OD) ratio of Stratifin in high-grade
      gliomas (World Health Organization [WHO] grade III/IV) was lower than in low
      grade tumors (WHO grade I/II, p=0.026). In addition, statistical analysis showed
      that patients expressing a high level of Stratifin have favorable overall
      survival rates relative to those expressing a low level of this protein. Cox
      multi-factor analysis showed that Stratifin (p=0.02) was an independent prognosis
      factor for human gliomas. Our results provide convincing evidence that the
      expression of Stratifin is down-regulated in human gliomas. Its expression level
      is correlated with the clinicopathological parameters and prognosis in patients
      with gliomas. Pending validation targeting, Stratifin might also be a novel
      opportunity to improve the therapy of this tumor.

PMID- 21940112
TI  - Demonstration of vasculogenic mimicry in astrocytomas and effects of Endostar on
      U251 cells.
AB  - Angiogenesis is an important process for the cell growth of normal and tumor
      tissues. Vasculogenic mimicry (VM) is a newly described vascular network
      structure that was first described in aggressive melanomas. To find out whether
      VM also exists in astrocytomas and to examine its clinical significance, we
      studied 80 malignant astrocytoma samples using immunohistochemistry coupled with
      periodic acid-Schiff (PAS) staining. To explore the possible therapeutic methods
      of anti-VM formation, we cultured astrocytoma cells using three-dimensional
      Matrigel and investigated the effects of Endostar, an endothelial cell growth
      inhibitor, on astrocytoma cell growth, invasion, and VM formation. VM structures
      were found in 8 samples of malignant astrocytomas, seven of which were grade IV
      astrocytomas. Glioblastoma U251 cells cultured in Matrigel formed vessel-like
      loops and networks, mimicking the features of VM in vivo, whereas such structures
      were not found in cultured normal astrocytes or well-differentiated astrocytoma
      SHG44 cells. In addition, treatment with Endostar led to a dose- and time
      dependent inhibition of proliferation and invasion of both U251and SHG44 cells,
      but VM formation by U251 cells in vitro was not prominently affected. In
      conclusion, VM is frequently detected in aggressive glioblastomas, and the
      presence of VM may constitute a new predictor for poor prognosis in astrocytoma
      patients. Although Endostar has broad anti-tumor effects due to anti-angiogenesis
      and anti-tumor cell mechanisms, its inhibitory effects on VM formation by
      U251cells in vitro are not remarkable.

PMID- 21940113
TI  - Development of the M. D. Anderson Cancer Center gynecologic applicators for the
      treatment of cervical cancer: historical analysis.
AB  - PURPOSE: To provide historical background on the development and initial studies
      of the gynecological (gyn) applicators developed by Dr. Gilbert H. Fletcher, a
      radiation oncologist and chairperson from 1948 to 1981 of the department at the
      M.D. Anderson Hospital (MDAH) for Cancer Research in Houston, TX, and to
      acknowledge the previously unrecognized contribution that Dr. Leonard G.
      Grimmett, a radiation physicist and chairperson from 1949 to 1951 of the physics
      department at MDAH, made to the development of the gynecological applicators.
      METHODS AND MATERIALS: We reviewed archival materials from the Historical
      Resource Center and from the Department of Radiation Physics at The University of
      Texas M. D. Anderson Cancer Center, as well as contemporary published papers, to
      trace the history of the applicators. CONCLUSIONS: Dr. Fletcher's work was
      influenced by the work on gynecologic applicators in the 1940s in Europe,
      especially work done at the Royal Cancer Hospital in London. Those efforts
      influenced not only Dr. Fletcher's approach to the design of the applicators but
      also the methods used to perform in vivo measurements and determine the dose
      distribution. Much of the initial development of the dosimetry techniques and
      measurements at MDAH were carried out by Dr. Grimmett.

PMID- 21940114
TI  - [Lessons and impact of two audits on postpartum hemorrhages in 24 maternity
      hospitals of the network "Securite Naissance - Naitre Ensemble" in "Pays-de-la
      Loire" area].
AB  - OBJECTIVES: The aim of the study is to assess the compliance rate of treatment of
      postpartum hemorrhage (PPH) according to guidelines developed by the CNGOF within
      our network by a first audit, and evaluate the impact of this first audit by
      conducting a second audit. METHODS: An initial audit of resources and management
      of postpartum hemorrhage (PPH) was conducted in 2006-2008 in 24 maternity
      hospitals of the Pays-de-la-Loire. The audit had identified six areas for
      improvement. A second audit was implemented in 2009-2010 to evaluate the actions
      of prevention and measure changes in the management of PPH. Two interns have
      distributed the 24 maternity homes and moved in each hospital to see 10 cases of
      vaginal delivery (VD) (section "Prevention"), and the last cases of PPH following
      a VD. The results are in compliance rate compared to the repository of the HAS in
      2004. RESULTS: The first audit was conducted on 101 PPH in total. It has allowed
      us to propose corrective actions to the 24 maternity hospitals: leaf specific
      monitoring, reporting amounts of blood loss, transfusion on these clinical
      criteria without waiting for the blood cell counts, indicating more frequent and
      rapid sulprostone, set for maternity hospitals without surgical skill an
      agreement with a visceral surgery department, and avoid maternal transfers for
      PPH. For the second audit, the compliance rate of the preventive aspect was 73%
      (95: 71-75%) of 239 cases of BA with variations according to maternity from 48 to
      93%. Compliance rates according to the criteria were: 99% obstetric
      consultations, 98% for anesthesia, 92% for hemoglobin, 77% for the group card
      available in the record, 89% agglutinins, 35% for the notification of the
      installation of bag, 36% for the notification of the amount of blood lost, 69%
      for the supervisor within two hours, and 64% for the directed delivery. For
      component "Support", the overall compliance rate was 81% (95: 79-83%) of 118 PPH
      AVB, and 85% in the 71 uterine atonies in 21 pregnancies (3 had no HPP during the
      period) with variations according to maternity from 51 to 93%. Conformities
      compared with the first audit were: improvement of time noted PPH (66 and 85%),
      initiation of a leaf-specific monitoring (0% and 87%), equivalence of appeals
      responders (86 and 88%), improving the amount of blood noted (51 and 67%),
      equivalent to the practice of evacuation of retained placenta (88 and 91%),
      decreased prescription of antibiotics (83 and 71%). For only uterine atony
      (n=71), there was a slight improvement in the prescription of sulprostone within
      30 minutes (53 and 58%), and improved decision within 2 hours (47 and 69%).
      Finally, there was no connection rates in the two components (r=0.32, p=0.15).
      Criteria associated with good compliance were calculated. CONCLUSION: There is a
      general improvement in prevention and care, with critical points and persistent
      disparities between pregnancies. In the aftermath of the completion of the audit,
      the overall results were sent to officials with the rank of each maternity,
      inviting each responsible to analyze weaknesses and implement corrective actions.
      Further action is planned within the network.

PMID- 21940115
TI  - Formal and informal substance use treatment utilization and alcohol abstinence
      over seven years: is the relationship different for blacks and whites?
AB  - BACKGROUND: This study examines whether the effects of formal substance use
      treatment utilization and Alcoholics Anonymous (AA) on 30-day abstinence vary for
      black versus white Americans. METHODS: The current analysis utilizes data from a
      longitudinal sample of 1013 black and white, dependent and problem drinkers
      across a 7-year period. Participants were identified through a probability survey
      in the general population and consecutive intakes in chemical dependency
      treatment programs in a California County. Generalized Estimating Equations
      assessing interactions between race and treatment utilization incorporated
      variables from four post-baseline interviews, controlling for baseline variables.
      RESULTS: Formal treatment utilization was associated with 30-day abstinence
      (OR:1.6, 95%CI: 1.3, 2.1), yet this relationship did not differ for blacks and
      whites. In contrast, there was a significant interaction between AA utilization,
      race and 30-day abstinence. While both whites and blacks who attended AA were
      more likely to report 30-day abstinence compared to their non-AA attending
      counterparts (white OR:4.0, 95%CI: 3.2-5.1 and black OR:2.2, 95%CI: 1.5-3.2), the
      relationship was stronger for whites. Among those who did not attend AA, blacks
      were more likely than whites to be abstinent. Post hoc analyses suggest that
      these latter findings may be related to greater religiosity and "drier" social
      networks among black Americans. CONCLUSIONS: While utilization of formal
      treatment may yield similar benefits for blacks and whites, AA utilization may be
      more important for maintaining abstinence among whites than blacks. Future
      research should investigate racial differences in social network drinking
      patterns and religious reinforcement of sobriety, and the role these may play in
      AA outcomes.

PMID- 21940116
TI  - Visna/Maedi virus genetic characterization and serological diagnosis of infection
      in sheep from a neurological outbreak.
AB  - An extensive outbreak characterized by the appearance of neurological symptoms in
      small ruminant lentivirus (SRLV) infected sheep has been identified in Spain, but
      the genetic characteristics of the strain involved and differential diagnostic
      tools for this outbreak remain unexplored. In this work, 23 Visna-affected
      naturally infected animals from the outbreak, 11 arthritic animals (both groups
      presenting anti-Visna/Maedi virus serum antibodies), and 100 seronegative animals
      were used. Eight of the Visna-affected animals were further studied post-mortem
      by immunohistochemistry. All had lesions in spinal cord, being the most affected
      part of the central nervous system in six of them. A representative strain of the
      outbreak was isolated. Together with other proviral sequences from the outbreak
      the virus was assigned to genotype A2/A3. In vitro culture of the isolate
      revealed that viral production was slow/low in fibroblast-like cells but it was
      high in blood monocyte-derived macrophages. The long terminal repeat (LTR) of the
      viral genome of this isolate lacked an U3-duplication, but its promoter activity
      in fibroblast-like cells was normal compared to other strains. Thus, viral
      production could not be inferred from the LTR promoter activity in this isolate.
      Analysis of the viral immunodominant epitopes among SRLV sequences of the
      outbreak and other known sequences allowed the design of a synthetic SU peptide
      ELISA that detected the Visna affected animals, representing a tool of
      epidemiological interest to control viral spread of this highly pathogenic
      strain.

PMID- 21940117
TI  - Oral administration of Salmonella enterica serovar Typhimurium expressing swine
      interleukin-18 induces Th1-biased protective immunity against inactivated vaccine
      of pseudorabies virus.
AB  - Enhancing and/or modulating innate and adaptive immunity by cytokines appears to
      be greatly useful to provide effective protective immunity against infectious
      diseases. However, an effective delivery system for mass administration in
      livestock industry is needed because of limitations such as cost, labor, time,
      and protein stability. Here the immunomodulatory functions of swine interleukine
      18 (swIL-18), known as IFN-gamma-inducing factor (IGIF), were evaluated in a
      vaccination model of pseudorabies virus (PrV) using attenuated Salmonella
      enterica serovar Typhimurium as the oral delivery system. The oral administration
      of S. enterica serovar Typhimurium expressing swIL-18 prior to vaccination with
      inactivated PrV vaccine induced enhanced levels of serum PrV-specific IgG and its
      IgG2 isotype, compared to administration of S. enterica serovar Typhimurium
      harboring the empty vector. Furthermore, S. enterica serovar Typhimurium
      expressing swIL-18 mounted Th1-biased cellular immune responses against PrV
      antigen, as evaluated by the production of IFN-gamma and IL-4 from peripheral
      blood mononuclear cells of piglets. Subsequently, Th1-biased immunity induced by
      S. enterica serovar Typhimurium expressing swIL-18 showed rapid response and
      rendered piglets displayed more alleviated clinical signs following the virulent
      PrV challenge. Also, this alleviation of clinical signs was further confirmed by
      the reduction of nasal excretion of PrV after challenge. The present study
      demonstrates the extended use of immunomodulatory functions of swIL-18 orally
      delivered by attenuated S. enterica serovar Typhimurium.

PMID- 21940118
TI  - Acute phase response in cattle infected with Anaplasma marginale.
AB  - This study was undertaken to evaluate the acute phase responses via the
      assessment of the concentration of serum sialic acids (total, lipid bound and
      protein bound), inflammatory mediators (IFN-gamma and TNF-alpha) and acute phase
      proteins (Hp and SAA) in 20 adult crossbred cattle naturally infected by
      Anaplasma marginale. The infected animals were divided into 2 subgroups on the
      basis of parasitemia rate (<20% and >20%). Also, as a control group, 10
      clinically healthy cattle from the same farms were sampled. Our data revealed
      significant decreases in red blood cell count (RBC), hematocrite (PCV) and
      hemoglobine (Hb) in infected cattle compared to healthy ones. Conversely, the
      concentrations of Hp, SAA, ceruloplasmin, fibrinogen, serum sialic acids and the
      circulatory IFN-gamma and TNF-alpha were increased in the diseased cattle
      (P<0.05). In addition, it was evident that the progression of parasitemia in
      infected cattle did not induce any significant alterations in the hematological
      indices (RBCs, PCV and Hb) and the concentrations of Hp, SAA, ceruloplasmin and
      fibrinogen. SAA was the most sensitive factor to change in the diseased cattle.
      Therefore, increase in SAA concentration may be a good indicator of inflammatory
      process in cattle naturally infected with Anaplasma marginale.

PMID- 21940119
TI  - Concentrations of circulating hormones during the interval between pulses of a
      PGF2alpha metabolite in mares and heifers.
AB  - The temporal relationship of several hormones to a metabolite of prostaglandin
      F2alpha (PGFM) was studied in mares and heifers from the beginning of the first
      PGFM pulse during luteolysis to the end of the second pulse. Mares (n=7) were
      selected with a 9-h interval between the peaks of the two pulses. In mares,
      estradiol-17beta (estradiol) increased (P<0.05) within each PGFM pulse and
      plateaued for a mean of 6h between the pulses, resulting in a stepwise estradiol
      increase. Progesterone decreased linearly (P<0.0001) throughout the intra-pulse
      and inter-pulse intervals of PGFM. In heifers (n=6), inter-pulse intervals were
      variable, and therefore Hours 1-4 of the first pulse (Hour 0=PGFM peak) and Hours
      -4 to -1 of the second pulse were used to represent the mean 8-h interval between
      peaks of the two pulses. Estradiol increased (P<0.05) during the ascending
      portion of each PGFM pulse and then decreased (P<0.05) beginning at Hour -1 of
      the first PGFM pulse and Hour 0 of the second pulse. The 1-h delay during the
      second pulse was accompanied by an apparent increase in PRL. A transient decrease
      in estradiol occurred in individuals between PGFM pulses at a mean of 5h after
      the first PGFM peak, concomitant with a transient LH increase (P<0.05). Results
      indicated that estradiol plateaued in mares and fluctuated in heifers during the
      interval between PGFM pulses. Heifers also showed temporal relationships between
      estradiol and LH and apparently between estradiol and PRL.

PMID- 21940121
TI  - The reciprocal relationship between menopausal symptoms and depressive symptoms:
      A 9-year longitudinal study of American women in midlife.
AB  - OBJECTIVES: The present study sought to examine: (a) the association between
      depressive symptoms among pre-menopausal and peri-menopausal women and subsequent
      difficulty with menopausal symptoms; and (b) the relationship between initial
      problems with menopausal symptoms and subsequent levels of depressive symptoms.
      STUDY DESIGN: Prospective Longitudinal Regression Analysis (n=986) of survey data
      from a national sample of non-institutional women in midlife (mean age=39.9 years
      at Time 1). MAIN OUTCOME MEASURES: Menopausal symptoms and symptoms of
      depression. RESULTS: Initial levels of depressive symptoms predicted 9-year
      follow-up levels of menopausal symptoms controlling for initial menopausal
      symptoms and demographic covariates (beta=.074; t(980)=2.425; p<.05). Initial
      levels of menopausal symptoms predicted follow-up levels of depressive symptoms
      controlling for initial depressive symptoms and demographic covariates (beta=110;
      t(980)=3.442; p<.001). CONCLUSIONS: Women who have more symptoms of depression in
      their early 40's may be at heightened risk for problems with the menopausal
      transition. Conversely, efforts to address more severe symptoms of menopause may
      help to reduce the onset of depressive symptoms among middle aged women.

PMID- 21940120
TI  - Influence of insulin-like growth factor-binding proteins-2 and -3 in the
      pathogenesis of cystic ovarian disease in cattle.
AB  - Ovarian cysts are one of the major causes of infertility in dairy cows. The
      development is associated with an endocrine imbalance in the hypothalamo
      hypophyseal-gonadal axis in which endocrine factors participate in follicular
      growth and differentiation and in the secretion of ovarian hormones. Insulin-like
      growth factor family are essential local regulators of ovarian follicle
      development and functionality and actions are mediated by binding protein
      activity. The aim of the present study was to analyze the expression of IGFBP-2
      and IGFBP-3 in developing follicles of normal estrous cycling animals and with
      spontaneous and induced cystic ovarian disease (COD) to determine IGF
      bioavailability. The mRNA of IGFBP-2 and IGFBP-3 in follicular walls was
      quantified by reverse transcription-polymerase chain reaction (RT-PCR) and in
      situ hybridization. Protein expression was analyzed by immunohistochemistry. The
      results demonstrated reduced amounts of mRNA of both IGFBPs in the granulosa
      cells of ovarian follicles of animals with COD (P<0.05). The present study
      suggests that the IGF system or imbalances between IGFs and IGFBPs may be
      involved in COD of cattle.

PMID- 21940122
TI  - Permanent teeth development in a Spanish sample. Application to dental age
      estimation.
AB  - The purpose of this study is to clarify the chronology of different stages of
      dental development, according to Demirjian, in a sample of Spanish children,
      which will enable us to build a database that will be used as a reference in
      regard to the dental development of individuals of our socio-geographic
      environment. In the same studied sample, a calculation of the dental age
      according to Demirjian was carried out. This study was conducted in a final
      sample consisting of 1010 orthopantograms, corresponding to Spanish children (485
      boys and 525 girls) ages 2-16. Comparing the age of onset of the different stages
      among the children, evidence was found that girls had an earlier general
      development than boys. These differences were only statistically significant in
      teeth and concrete stages. The canine teeth revealed greater gender dimorphism,
      with significant differences in all stages compared with the upper canines. The
      method proposed by Demirjian for dental age calculation resulted in a significant
      overestimation of dental age in relation to the chronological age in boys
      (average of 0.87 years) and girls (average of 0.55 years). Data from this study
      may be used as reference for dental maturity, as well as a standard for
      estimating age in Spanish children.

PMID- 21940123
TI  - Accuracy of different dental age estimation methods on Turkish children.
AB  - Tooth development is widely used to estimate age or maturation. Dental age
      estimation is so important for various research works. Numerous methods have been
      described to estimate dental age based on the dental maturation. The aims of this
      study were to decide the best method to estimate dental age on Turkish children
      by reviewing several methods and to illustrate the differences among the methods
      and to assist future studies. The records of Turkish children between the ages of
      7 and 13 years who visited the Department of Pediatric Dentistry of the Faculty
      of Dentistry of the Suleyman Demirel University in Isparta, Turkey were reviewed
      and a total of 425 healthy children with complete records, satisfactory panoramic
      radiographs, similar socio-economic background and ethnic origin were included.
      Panoramic radiographs were examined with Nolla's, Haavikko's and Demirjian's
      methods. Dental age was calculated for each method, and the differences between
      the estimated dental age and the chronological age were compared with paired t
      test and Wilcoxon signed rank test. The accuracy of three methods was obtained
      with ICC (intraclass correlation coefficient). An under-estimation of the dental
      age was observed by using Nolla's and Haavikko's methods (boys -0.53+/-0.95,
      girls -0.57+/-0.91, both -0.54+/-0.93; boys -0.60+/-0.80, girls -0.56+/-0.81,
      both -0.58+/-0.80, respectively) and an over-estimation of the dental age was
      observed by using Demirjian's method (boys 0.52+/-0.86, girls 0.75+/-0.90, both
      0.64+/-0.89). Haavikko's method was more accurate in the dental age estimation
      compared to the other methods. All of the three methods are not completely
      suitable for Turkish children and establishment of the population-specific
      standards is essential and crucial.

PMID- 21940124
TI  - Maturation of EEG oscillations in children with sodium channel mutations.
AB  - Dravet syndrome (DS) is a severe epileptic encephalopathy beginning in infancy in
      which children have difficult to control seizures and cognitive impairment. The
      majority of children with DS carry mutations of the gene Scn1a, which codes for
      the alpha subunit of the type 1 voltage-gated sodium channel and is important for
      the function of interneurons. Interneurons have a critical role in the generation
      of brain rhythms involved in cognitive processing. We hypothesized that children
      with DS with Scn1a mutations would have abnormal oscillatory activity. To address
      this hypothesis, we used EEG power spectral analysis during the wakening to
      determine if frequency and power are altered in 23 EEGs from 12 children with DS
      compared to 18 age-matched controls. While there were few differences between the
      EEG power spectra in DS and controls in children under 2years, in older children
      group differences were apparent. In DS children between 3 and 5years there were
      significant decreases in percentage of alpha power compared to controls and in DS
      children over age 6years there was a marked increase of theta and decrease of
      alpha compared to controls. Developmental status paralleled the power spectral
      analysis with an increasing likelihood of having severe cognitive problems with
      increasing age. These results demonstrate that Scn1a mutations result in an age
      dependent alteration in oscillatory process. Such abnormalities in developmental
      progression of oscillations may play an important role in poor cognitive
      development in children with DS.

PMID- 21940125
TI  - [Increasing trends in screening for addictives behaviors among general
      practitioners in France].
AB  - BACKGROUND: Make an inventory of screening of addictive behaviours among general
      practice since the end of the 1990s. METHODS: A representative sample of 2,083
      general practitioners was surveyed in 2008/2009. They were asked about their
      prevention practices. RESULTS: Two thirds of the general practitioners (GPs)
      reported discussing tobacco consumption at least once with each patient. This
      assessment was less systematic for alcohol (23% of GPs) and cannabis (8% of GPs).
      Approximatively 70% reported addressing cannabis or alcohol use issues only with
      patients at risk. One third reported using tobacco smoking screening
      questionnaires, while there were only 6% in 2003. Only 13% of GPs used alcohol
      standardized questionnaires, a clear rise since 1998 (1.4% in 1998, 2.0% in
      2003). Using alcohol standardized screening tests was more frequent among GPs
      belonging to a drug addiction network, but no significant link was found with
      gender, age or area. Only 2% of GPs used cannabis use screening tests. The care
      for cannabis users seemed particularly linked to the practitioners' inclination
      to discuss this issue without waiting for a demand arising from the patient. The
      proportion of practitioners reporting helping patients kick their nicotine
      addiction in the last seven days proved stable since 2003, after a very
      significant increase between 1998 and 2003. The proportion of GPs reporting
      seeing a patient for an alcoholic weaning (52%) was stable since 1998.
      CONCLUSION: This study illustrates the development of addiction care practices
      integrating smoking cessation help and, to a more limited extent, screening of
      alcohol and cannabis abuse, evidenced by the expanded application of standardized
      questionnaires in general practice. Consideration given to cannabis and alcohol
      use assessment appeared correlated to GPs feeling at ease with addressing drug
      use issues, this feeling being linked to their ability to rely on institutional
      directives or validated screening tools. It seems thus important to encourage the
      implementation of a health educational approach including early screening and
      brief intervention during consultation.

PMID- 21940126
TI  - [Using French national health insurance data for non-specific monitoring on
      Reunion Island].
AB  - BACKGROUND: In Reunion Island, non-specific surveillance developed mainly in 2009
      and was based on the activity of hospital emergency department, emergency calls
      and mortality. From March 2010, a new surveillance was implemented in
      collaboration between the Indian Ocean regional epidemiology unit and the
      regional office of the National Health Insurance. The system is based on the
      weekly number of general practitioner consultations and home visits by
      municipality. This article presents methods of using these data for non-specific
      monitoring in Reunion Island. MATERIALS AND METHODS: Data analyzed cover
      consultations and visits to general practitioners and pediatricians for each of
      the 24 municipalities. Data were received in week S+1 and were updated week by
      week following the flow of repayments. To perform weekly monitoring, determine
      monitoring impact and detect any unusual health event, a correction factor was
      thus calculated and applied for the overall data set and for each municipality.
      Received data covered 72% of the population of the island. RESULTS: Over the
      study period from 2005 to 2009, the monthly average of consultations was 80,000
      (min: 58,000 - max 12,0000). Two main peaks of activity were noticed throughout
      the island during the study period, the first one from weeks 4 to 9 of 2006 with
      a peak of 105,000 consultations in week 8 and the second one from weeks 34 to 41
      of 2009 with a peak of 120,000 consultations in week 35. CONCLUSION: The two
      peaks described in 2006 and 2009 respectively correspond to outbreaks of
      chikungunya and influenza A(H1N1) 2009. This monitoring study has two main
      advantages: an almost exhaustive data set corresponding to three-quarters of the
      Reunion Island population and the geographic analysis by municipality. Positioned
      alongside other monitoring networks, this system expands the indicators monitored
      reflecting varying uses of care.

PMID- 21940127
TI  - Relationship between psychosocial factors at work and incidence of perceived
      health problems in the GERICOTS cohort.
AB  - BACKGROUND: The objective of this study was to investigate the relationship
      between the incidence of health problems and the psychosocial work environment in
      a French occupational cohort. METHODS: Among the 2062 employees in the North of
      France who participated in the GERICOTS survey between 1999 and 2004, 1154
      subjects who kept the same full-time shift in the same firm during the study
      period (797 men and 357 women) were included. Job strain was assessed using
      Karasek's model--the strain profile (high psychological demand and low decision
      latitude) and the iso-strain profile (strain profile and low social support)--and
      Siegrist's model, Effort-Reward Imbalance (ERI) (high effort and low rewards).
      Perceived health status was assessed using the four dimensions of the Nottingham
      Health Profile (emotional reactions, sleep, social isolation, pain). The results
      are given by the odds ratio adjusted for age, occupational category, and size of
      firm. RESULTS: At baseline, higher prevalence of health problems was found in
      workers with job strain, e.g., between emotional reactions and iso-strain for
      men, OR=3.50 (2.19-5.60) and for women, 2.64 (1.39-5.04) or between sleep
      disorders and ERI for men, OR=2.41 (1.71-3.40) and for women, OR=2.41 (1.39
      4.20). Longitudinal analysis showed a significant relationship between incidence
      of health problems and level of job strain in 1999, e.g., between sleep disorder
      incidence and strain profile, OR=1.89 (1.16-3.06) and ERI, OR=2.20 (1.43-3.38).
      CONCLUSION: These results show a significant relationship between perceived
      health and job stress in 1999 but also between incidence of health problems
      between 1999 and 2004 and job strain in 1999.

PMID- 21940128
TI  - Feasibility of abdominal plain film images in evaluation suspected drug smuggler.
AB  - OBJECTIVE: Drug smuggling in the gastrointestinal tract has soared within the
      last 20 years. Though illegal substances in the gastrointestinal tract can be
      visualized with ultrasound, MRI and CT, the abdominal radiograph has by far
      remained the most frequently used way of detecting smuggled drugs. The purpose of
      the study was to evaluate the inter-radiologist interpretation error and the
      reliability of the abdominal radiograph in detecting smuggled drugs. MATERIALS
      AND METHODS: A total of 279 abdominal radiographs of suspected smugglers were
      classified by three radiologists as clearly positive or negative for drug
      smuggling. All available information about the cases was collected from the
      customs officers and police. RESULTS: Out of these cases 203 (73%) were
      interpreted as negative and 35 (13%) as positive by all three radiologists. In
      86% of the cases there was, therefore, an inter-radiological agreement in
      interpreting the images. In 41 (14%) cases, however, there was an inter
      radiologist disagreement. Kappa-value for inter-observer variability was 0.70.
      CONCLUSIONS: In up to a seventh of the abdominal radiographs the interpretation
      can be challenging even for an experienced radiologist. False positive
      interpretation can lead to innocent passengers being detained in vain. As
      negatively interpreted images usually result in releasing of the suspect, there
      is no way of knowing how many false negative occur. This makes the abdominal
      radiograph a suboptimal examination, and low dose CT should be considered as the
      screening modality for gastrointestinal drug smugglers.

PMID- 21940129
TI  - Environmental Vibrio parahaemolyticus DNA signatures validation.
AB  - Insignia is a novel DNA computational system which uses highly efficient
      algorithms to compare bacterial genomes and to identify specific DNA signatures
      to distinguish a target bacterium, or group of bacteria, from all other known
      bacterial species. It is currently being validated using different bacterial
      groups, including Vibrio spp. In this study, the genomic analysis by Insignia was
      conducted on Vibrio parahaemolyticus, a halophilic gram-negative bacteria which
      constitutes a leading cause of seafood-borne disease. Insignia was used to
      identify 37 V. parahaemolyticus-specific signatures and to design PCR assays to
      validate the representative signature sequences by TaqMan essays. The 37 assays
      targeted loci distributed around the genome and detected genes coding for
      hypothetical proteins and for proteins involved in adhesion, starvation and
      virulence. A panel of V. parahaemolyticus environmental strains isolated from the
      North Adriatic Sea (Italy) and from the Black Sea (Georgia) was used to validate
      the selected signatures. The signature assays revealed both sensitive and
      specific and the method allowed a more accurate identification of the tested
      bacterial strains at the species level when compared to biochemical and PCR
      standard methods. Using Insignia, it was possible to distinguish two different
      groups among the strains previously identified as V. parahaemolyticus: most of
      the strains were included in a "V. parahaemolyticus-like group" showing nearly
      all of the signatures assayed while a small group of 10 strains contained only a
      few of the signatures tested. By sequencing the 16S rDNA of this latter group, it
      was confirmed that they were not V. parahaemolyticus but in fact belonged to
      other Vibrio species. No significant genome-wide differences were detected
      between the strains isolated in Italy and in Georgia though the very different
      geographical origin.

PMID- 21940130
TI  - Branchiibius cervicis sp. nov., a novel species isolated from patients with
      atopic dermatitis.
AB  - Novel actinobacterial strains, PAGU 1247(T), PAGU 1251 and PAGU 1252, were
      isolated from the skin of atopic dermatitis patients and were characterized using
      a polyphasic approach. Phylogenetic analyses based on 16S rRNA gene sequences
      showed that these isolates were located within the family Dermacoccaceae. The
      most closely related species of PAGU 1247(T) in phylogenetic terms was
      Branchiibius hedensis Mer 29717(T), with 16S rRNA gene sequence similarity of
      99.6%, although the DNA-DNA relatedness value was less than 43.9%. Some
      biochemical traits, such as lipase (C14) and alpha-galactosidase activity, could
      distinguish these isolates from B. hedensis. Strain PAGU 1247(T) contained iso
      C(16:0) and brC(18:0) as the major fatty acids. The quinone system consisted of
      menaquinone MK-8(H(6) and H(4)). The G+C content of the genomic DNA was 67.6mol%.
      On the basis of its phenotypic properties and genetic distinctiveness, strains
      PAGU 1247(T), PAGU 1251 and PAGU 1252 represents a novel species of the genus
      Branchiibius, for which the name Branchiibius cervicis sp. nov. is proposed. The
      type strain is PAGU 1247(T) (=NBRC 106593(T)=DSM 24166(T)).

PMID- 21940131
TI  - Hepatic lipid composition analysis using 3.0-T MR spectroscopy in a steatotic rat
      model.
AB  - PURPOSE: To investigate the feasibility of in vivo assessment of hepatic lipid
      composition using 3.0-T proton magnetic resonance spectroscopy ((1)H-MRS) in a
      steatotic rat model and compare it to histopathological and biochemical
      assessment. MATERIALS AND METHODS: Hepatic steatosis was induced by feeding rats
      with a methionine/choline-deficient (MCD) diet for 1, 2, 3, 5 or 7 weeks (n=5 per
      group). At the end of the diet period, (1)H-MRS of the liver was performed, and
      rats were sacrificed for histopathological and biochemical assessment of the
      liver. Spectra were acquired in a single voxel (1.2 cc) using a point-resolved
      spectroscopic sequence with TE/TR=35/2000 ms and 64 signal acquisitions. From the
      MR spectra, peak area ratios were calculated to estimate hepatic lipid
      composition. RESULTS: During MCD diet periods, hepatic steatosis significantly
      increased on histopathology (P<.001). The (1)H-MRS measurements of total hepatic
      fat content [1.3/(1.3+4.65) ppm] correlated strongly with histological
      macrovesicular hepatic steatosis (r=0.93, P<.001) and with the biochemical total
      hepatic fatty acids (r=0.94, P<.001). Total unsaturated fatty acids [TUFA,
      5.4/(1.3+4.65) ppm] estimated with (1)H-MRS strongly correlated with the
      biochemical unsaturated fatty acids (r=0.90, P<.001). Polyunsaturated fatty acids
      [PUFA, 2.8/(1.3+4.65) ppm] estimated with (1)H-MRS strongly correlated with
      biochemical PUFA (r=0.91, P<.001). The proportion of total unsaturated fatty
      acids relative to the amount of total fatty acids (rTUFA, 5.4/1.3 ppm) measured
      with (1)H-MRS strongly correlated with the biochemical amount of unsaturated
      relative to total hepatic fatty acids (r=0.81, P<.001). The proportion of PUFA
      relative to the amount of total fatty acids (rPUFA, 2.8/1.3 ppm) measured with
      (1)H-MRS correlated with the biochemical amount of PUFA relative to total fatty
      acids (r=0.59, P=0.005,) and with the biochemical amount of omega-6 PUFA relative
      to total fatty acids (r=0.73, P<.001). PUFA at (1)H-MRS correlated with the
      histopathologically assessed degree of lobular inflammation in the liver (r=0.57,
      P=.001). CONCLUSION: 3.0 T (1)H-MRS is able to measure poly- and unsaturated
      hepatic fatty acids and this strongly correlates with biochemical assessment.
      This study provides evidence that 3.0-T (1)H-MRS is a noninvasive technique to
      assess hepatic lipid composition.

PMID- 21940132
TI  - Classification trees based on infrared spectroscopic data to discriminate between
      genuine and counterfeit medicines.
AB  - Classification trees built with the Classification And Regression Tree algorithm
      were evaluated for modelling infrared spectroscopic data in order to discriminate
      between genuine and counterfeit drug samples and to classify counterfeit samples
      in different classes following the RIVM classification system. Models were built
      for two data sets consisting of the Fourier Transformed Infrared spectra, the
      near infrared spectra and the Raman spectra for genuine and counterfeit samples
      of respectively Viagra((r)) and Cialis((r)). Easy interpretable models were
      obtained for both models. The models were validated for their descriptive and
      predictive properties. The predictive properties were evaluated using both cross
      validation as an external validation set. The obtained models for both data sets
      showed a 100% correct classification for the discrimination between genuine and
      counterfeit samples and 83.3% and 100% correct classification for the counterfeit
      samples for the Viagra((r)) and the Cialis((r)) data set respectively.

PMID- 21940133
TI  - The utility of the HeartSaver Sticker for maintaining correct hand position
      during chest compressions.
AB  - BACKGROUND: The importance of attaining correct hand position in cardiopulmonary
      resuscitation (CPR) instruction has not been emphasized as much as the
      significance of the compression performance. STUDY OBJECTIVES: This pilot study
      was performed to investigate the utility of a HeartSaver Sticker for maintaining
      correct hand position during chest compressions. METHODS: Fifty-one sophomore
      college students, training to become emergency medical technicians, were
      recruited. The students, having no previous experience using HeartSaver stickers,
      participated in this prospective, randomized simulation-based controlled study,
      which consisted of two groups: 1) with sticker (n=26), 2) without sticker (n=25).
      The 4*4-cm HeartSaver sticker marked with both vertical and horizontal center
      lines was used in this study. Proper sticker placement was such that the vertical
      line coincided with the mid-sternum of the chest, and the horizontal line aligned
      with the nipples. Participants performed adult basic life support by single
      rescuer according to the 2005 American Heart Association resuscitation
      guidelines. Skill assessment was also performed by these guidelines. RESULTS:
      Group 1 participants placed the HeartSaver sticker on the correct landmark within
      10 s of approaching the model. The compression rate and depth were not
      significantly different between the two groups. However, significant improvement
      in correct hand position was noticed when using the HeartSaver sticker. Correct
      hand position was 97.1% +/- 7.4% in group 1 and 85.9% +/- 21.5% in group 2
      (p=0.002). CONCLUSION: The HeartSaver sticker was useful in maintaining correct
      hand position during the single-rescuer CPR scenario because it provided easy
      recognition of that position when compressing after ventilations.

PMID- 21940134
TI  - Outcome of heroin-dependent adolescents presenting for opiate substitution
      treatment.
AB  - Because the outcome of methadone and buprenorphine substitution treatment in
      adolescents is unclear, we completed a retrospective cohort study of 100
      consecutive heroin-dependent adolescents who sought these treatments over an 8
      year recruitment period. The participants' average age was 16.6 years, and 54
      were female. Half of the patient group remained in treatment for over 1 year.
      Among those still in treatment at 12 months, 39% demonstrated abstinence from
      heroin. The final route of departure from the treatment program was via planned
      detox for 22%, dropout for 32%, and imprisonment for 8%. The remaining 39% were
      transferred elsewhere for ongoing opiate substitution treatment after a median
      period of 23 months of treatment. Males were more likely to exit via imprisonment
      (p < .05), but other outcomes were not predicted by gender. There were no deaths
      during treatment among these 100 patients who had a cumulative period of 129
      person years at risk. Our findings suggest that this treatment delivers
      reductions in heroin use and that one fifth of patients will exit treatment
      following detox completion within a 1- to 2-year time frame.

PMID- 21940135
TI  - Adding positive reinforcement in justice settings: acceptability and feasibility.
AB  - Although contingency management (CM) approaches are among the most promising
      methods for initiating drug abstinence (S. T. Higgins, S. M. Alessi, & R. L.
      Dantona, 2002; S. T. Higgins, S. H. Heil, & J. P. Lussier, 2004), adoption and
      implementation of CM protocols into treatment programs are both challenging and
      infrequent. In criminal justice agencies, where roughly 70% of clients report
      substance abuse issues (F. S. Taxman, K. L. Cropsey, D. W. Young, & H. Wexler,
      2007), CM interventions are virtually nonexistent. The Justice Steps (JSTEPS)
      study uses a longitudinal, mixed-method design to examine the implementation of a
      CM-based protocol in five justice settings. This article presents qualitative
      data collected during Phase 1 of the JSTEPS project regarding the acceptability
      and feasibility of CM in these justice settings. The study finds a level of
      acceptability (find CM tolerable) and feasibility (find CM suitable) within
      justice agencies, but with some challenges. These challenges are reflected in the
      following: (a) incorporating too many desired target behaviors into CM models;
      (b) facing intraorganizational challenges when designing CM systems; and (c)
      emphasizing sanctions over rewards despite the evidence-base for positive
      reinforcers. These findings have implications for advancing the dissemination,
      adoption, and implementation of evidence-based treatments (and CM in particular)
      in criminal justice settings.

PMID- 21940137
TI  - Expression pattern, ethanol-metabolizing activities, and cellular localization of
      alcohol and aldehyde dehydrogenases in human large bowel: association of the
      functional polymorphisms of ADH and ALDH genes with hemorrhoids and colorectal
      cancer.
AB  - Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are principal
      enzymes responsible for metabolism of ethanol. Functional polymorphisms of ADH1B,
      ADH1C, and ALDH2 genes occur among racial populations. The goal of this study was
      to systematically determine the functional expressions and cellular localization
      of ADHs and ALDHs in human rectal mucosa, the lesions of adenocarcinoma and
      hemorrhoid, and the genetic association of allelic variations of ADH and ALDH
      with large bowel disorders. Twenty-one surgical specimens of rectal
      adenocarcinoma and the adjacent normal mucosa, including 16 paired tissues of
      rectal tumor, normal mucosae of rectum and sigmoid colon from the same
      individuals, and 18 surgical mixed hemorrhoid specimens and leukocyte DNA samples
      from 103 colorectal cancer patients, 67 hemorrhoid patients, and 545 control
      subjects recruited in previous study, were investigated. The isozyme/allozyme
      expression patterns of ADH and ALDH were identified by isoelectric focusing and
      the activities were assayed spectrophotometrically. The protein contents of
      ADH/ALDH isozymes were determined by immunoblotting using the corresponding
      purified class-specific antibodies; the cellular activity and protein
      localizations were detected by immunohistochemistry and histochemistry,
      respectively. Genotypes of ADH1B, ADH1C, and ALDH2 were determined by polymerase
      chain reaction-restriction fragment length polymorphisms. At 33mM ethanol, pH
      7.5, the activity of ADH1C*1/1 phenotypes exhibited 87% higher than that of the
      ADH1C*1/*2 phenotypes in normal rectal mucosa. The activity of ALDH2-active
      phenotypes of rectal mucosa was 33% greater than ALDH2-inactive phenotypes at
      200MUM acetaldehyde. The protein contents in normal rectal mucosa were in the
      following order: ADH1>ALDH2>ADH3~ALDH1A1, whereas those of ADH2, ADH4, and
      ALDH3A1 were fairly low. Both activity and content of ADH1 were significantly
      decreased in rectal tumors, whereas the ALDH activity remained unchanged. The ADH
      activity was also significantly reduced in hemorrhoids. ADH4 and ALDH3A1 were
      uniquely expressed in the squamous epithelium of anus at anorectal junctions. The
      allele frequencies of ADH1C*1 and ALDH2*2 were significantly higher in colorectal
      cancer and that of ALDH2*2 also significantly greater in hemorrhoids. In
      conclusion, ADH and ALDH isozymes are differentially expressed in mucosal cells
      of rectum and anus. The results suggest that acetaldehyde, an immediate
      metabolite of ethanol, may play an etiological role in pathogenesis of large
      bowel diseases.

PMID- 21940136
TI  - Motivational and mindfulness intervention for young adult female marijuana users.
AB  - This pilot study tested the efficacy of a brief intervention using motivational
      interviewing (MI) plus mindfulness meditation (MM) to reduce marijuana use among
      young adult females. Thirty-four female marijuana users between the ages of 18
      and 29 were randomized to either the intervention group (n = 22), consisting of
      two sessions of MI-MM, or an assessment-only control group (n = 12). The
      participants' marijuana use was assessed at baseline and at 1, 2, and 3 months
      posttreatment. Fixed-effects regression modeling was used to analyze treatment
      effects. Participants randomized to the intervention group were found to use
      marijuana on 6.15 (z = -2.42, p = .015), 7.81 (z = -2.78, p = .005), and 6.83 (z
      = -2.23, p = .026) fewer days at Months 1, 2, and 3, respectively, than controls.
      Findings from this pilot study provide preliminary evidence for the feasibility
      and effectiveness of a brief MI-MM for young adult female marijuana users.

PMID- 21940138
TI  - Breast conservative surgery after neoadjuvant chemotherapy in breast cancer
      patients: comparison of two tumor localization methods.
AB  - AIMS: The key to surgical planning for breast conservative treatment (BCT) after
      neoadjuvant chemotherapy (NAC) is tumor localization. Tumor marking can be
      performed using either skin tattoo or metallic marker. The objective of this
      study is to compare both types of tumor localization markers and to assess which
      techniques improve BCT in achieving a complete resection without compromise
      margins. METHODS: 149 patients between 1999 and 2009 were eligible for the study.
      The skin tattoo group (TG) included 118 patients and the metallic marker group
      (MG) included 31 patients. Both markers were placed before starting NAC. RESULTS:
      Median clinical tumor volume was 10.3 cm(3) in the TG and 22.4 cm(3) in the MG (p
      = 0.051). After NAC treatment, there were no significant statistically
      differences in both groups regarding complete clinical response, partial clinical
      response, and complete and partial pathological response. Median pathological
      tumor volume was: 0.8 cm(3) in the TG and 0.69 cm(3) in the MG (p = 0.8).
      Lumpectomy volume was bigger in the TG (268 cm(3)) than MG (143 cm(3)); p <
      0.004. There were no statistically significant differences when comparing margin
      status. CONCLUSIONS: Lumpectomy guided with metallic marker after NAC allows
      lower excision of breast tissue without compromising margins. Having similar
      pathologic response between groups, skin tattoo leads to excise larger volume of
      tissue adding no benefits to the surgery. With the increasing pathologic complete
      responses to NAC, patients who are candidates for BCT after NAC will benefit from
      marking the tumor with metallic markers.

PMID- 21940139
TI  - Sleep apnea-hypopnea syndrome and acute coronary syndrome - an association not to
      forget.
AB  - AIM: To evaluate the prevalence of Sleep Apnea-Hypopnea Syndrome (SAHS) in
      patients who were admitted with Acute Coronary Syndrome (ACS) to the Coronary
      Care Unit (CCU) and the clinical predictors of SAHS in patients with ACS and to
      compare the results of the simple sleep test (SST) with polysomnography (PSG).
      METHODS: This was a prospective study that included patients who were admitted to
      the CCU with ACS, which was confirmed by coronary angiography. Demographic and
      anthropometric data, cardiovascular risk factors and measures on the Epworth
      Sleepiness Scale were collected. The SST was conducted with the ApneaLink(TM)
      device during hospitalization or after discharge. Patients with an apnea-hypopnea
      index (AHI) >= 10/h were invited to participate in PSG. RESULTS: Ninety-one
      patients with ACS were consecutively included over 4 months. Of the fifty-eight
      patients who completed the study 43 (74.1%) were male. The mean age was 61.7+/
      12.2 years, and the mean body mass index was 27.4+/-3.5 kg/m(2). The median time
      for SST performance was 17.5 days. This study was compatible with SAHS in 25
      cases (43.1%). Patients who had an AHI >= 10/h in the SST were submitted to PSG
      and SST simultaneously. The median interval between the ACS and the execution of
      PSG was 30 days. PSG confirmed that all of the cases that were detected by SST
      were positive. CONCLUSION: In our study, we found a high prevalence of SAHS in
      patients who were admitted to the CCU with ACS (43.1%). These results support the
      need for SAHS screening in patients who are hospitalized with ACS. The SST may
      have a role in the screening of SAHS in this population.

PMID- 21940140
TI  - Visual outcomes and patient satisfaction after cataract surgery with toric
      multifocal intraocular lens implantation.
AB  - PURPOSE: To evaluate visual outcomes and patient satisfaction after toric
      multifocal intraocular lens (IOL) implantation in patients with cataract and
      corneal astigmatism. SETTING: University Eye Clinic Maastricht, The Netherlands.
      DESIGN: Cohort study. METHODS: Patients with cataract, corneal astigmatism, and a
      motivation for spectacle independency had cataract surgery with implantation of a
      toric diffractive multifocal IOL (AT Lisa). Three months postoperatively, the
      uncorrected distance (UDVA), intermediate (UIVA), and near (UNVA) visual
      acuities; corrected distance, intermediate, and near visual acuities; residual
      refractive astigmatism; defocus curve; contrast sensitivity; and patient
      satisfaction were evaluated. RESULTS: Forty-five eyes of 25 patients were
      enrolled. Postoperatively, the mean UDVA was 0.04 logMAR +/- 0.15 (SD) and 98% of
      eyes achieved a UDVA of 20/40 or better. The mean UNVA was 0.20 +/- 0.16 logMAR
      and the mean UIVA (at 60 cm), 0.40 +/- 0.16 logMAR. Residual refractive
      astigmatism of -1.00 diopter or less was achieved in approximately 90% of eyes.
      Contrast sensitivity levels were high. Approximately 50% of patients reported
      moderate glare, halos, and starburst symptoms. Spectacle independency for
      distance and near vision was achieved by 95% of patients and 79% of patients,
      respectively. CONCLUSIONS: Toric IOL implantation in patients with cataract and
      corneal astigmatism provided good distance and near visual outcomes and
      acceptable intermediate visual outcomes, allowing patients with considerable
      amounts of corneal astigmatism to achieve spectacle independence at distance and
      near. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in
      any material or method mentioned. Additional disclosures are found in the
      footnotes.

PMID- 21940141
TI  - Cataract surgery with primary intraocular lens implantation in children with
      uveitis: long-term outcomes.
AB  - PURPOSE: To report long-term outcomes of cataract surgery with primary posterior
      chamber intraocular lens (IOL) implantation in children with chronic uveitis.
      SETTING: Department of Ophthalmology, Pitie-Salpetriere Hospital, Paris, France.
      DESIGN: Case series. METHODS: This case series comprised patients younger than 16
      years with chronic uveitis who underwent phacoemulsification with primary
      implantation of a heparin surface-modified poly(methyl methacrylate) posterior
      chamber IOL in the capsular bag. The intraocular inflammation was fully
      controlled for at least 3 consecutive months before surgery in all cases. The
      main outcome measures were final corrected distance visual acuity (CDVA),
      postoperative inflammation, complications, and level of immunosuppressive
      treatment. RESULTS: Twenty-two eyes of 16 children (7 girls, 9 boys; median age
      at surgery 9.5 years old) were included. Underlying uveitic entities were
      juvenile idiopathic arthritis in 9 patients; idiopathic uveitis in 4; and Behcet
      disease, sarcoidosis, and varicella zoster-associated uveitis in 1 patient each.
      The final CDVA was 0.3 logMAR or better in all cases. Postoperative complications
      included posterior capsule opacification requiring laser capsulotomy in 2 eyes,
      glaucoma in 4 eyes, and cystoid macular edema/macular dysfunction in 3 eyes. The
      mean dose of oral prednisone was 29.5 mg/day preoperatively and 8.13 mg/day at
      the last follow-up. The median follow-up was 6 years (range 5 to 19 years).
      CONCLUSION: The results indicate that uveitis is not a formal contraindication to
      primary IOL implantation in the management of pediatric cataract surgery in cases
      with full control of intraocular inflammation. FINANCIAL DISCLOSURE: No author
      has a financial or proprietary interest in any material or method mentioned.

PMID- 21940142
TI  - Capsular block syndrome associated with femtosecond laser-assisted cataract
      surgery.
AB  - We report intraoperative capsular block syndrome occuring during the first 50
      femtosecond laser-assisted cataract surgeries performed in our facility. Two
      patients had uneventful combined laser fragmentation, capsulotomy, and corneal
      incision procedures. In both cases, following transfer to the operating room and
      manual removal of the laser-cut capsulotomy, posterior capsule rupture was noted
      during hydrodissection, resulting in posterior dislocation of the lens. Pars
      plana vitrectomy, removal of the crystalline lens, and sulcus implantation of an
      intraocular lens were performed in both patients with good visual outcomes.
      Femtosecond laser-assisted cataract surgery changes the intraoperative
      environment with the generation of intracapsular gas and laser-induced changes in
      the cortex. With awareness of the changed intraocular environment following laser
      lens fragmentation and capsulotomy and a modification of the surgical technique,
      no additional cases of intraoperative CBS have been seen in more than 600 laser
      assisted cataract surgery procedures performed to date at our facility. FINANCIAL
      DISCLOSURE: No author has a financial or proprietary interest in any material or
      method mentioned. Additional disclosure is found in the footnotes.

PMID- 21940143
TI  - Corneal endothelial cell loss during phacoemulsification: bevel-up versus bevel
      down phaco tip.
AB  - PURPOSE: To compare corneal endothelial cell loss during cataract extraction by
      phacoemulsification with 2 different phaco-tip positions. SETTING: Ophthalmic
      Research Center and Department of Ophthalmology, Labbafinejad Medical Center,
      Shahid Beheshti Medical University, Tehran, Iran. DESIGN: Randomized clinical
      trial. METHODS: Eyes scheduled for cataract extraction were randomly assigned
      stop-and-chop phacoemulsification with the phaco tip in the conventional bevel-up
      position or with the phaco tip in the bevel-down position. During surgery, the
      effective phacoemulsification time (EPT) was recorded. Preoperative endothelial
      cell parameters were compared with measurements taken 3 months postoperatively.
      RESULTS: Each group comprised 30 eyes (30 patients). There were no statistically
      significant differences in age, sex, anterior chamber depth, axial length, or EPT
      between the 2 groups. The mean preoperative endothelial cell density (ECD) was
      2544 cells/mm(2) +/- 64 (SD) in the bevel-up group and 2471 +/- 59 cells/mm(2) in
      the bevel-down group (P=.610). Postoperatively, both groups had a significant
      decrease in ECD. The mean endothelial cell loss was 5.9% in the bevel-up group
      and 13.6% in the bevel-down group (P=.012). The percentage of hexagonal cells and
      coefficient of variation in cell size were not different between the 2 groups
      preoperatively or postoperatively; however, after surgery, there was a
      significant decrease in the percentage of hexagonal cells in both groups.
      CONCLUSION: Corneal endothelial cell loss during phacoemulsification was
      significantly higher when the phaco tip was in the bevel-down position than in
      the conventional bevel-up position. FINANCIAL DISCLOSURE: No author has a
      financial or proprietary interest in any material or method mentioned.

PMID- 21940144
TI  - Vowel- and text-based cepstral analysis of chronic hoarseness.
AB  - OBJECTIVES/HYPOTHESIS: Automatic voice evaluation is usually performed on stable
      sections of sustained vowels, which often cannot capture hoarseness properly. The
      measures cepstral peak prominence (CPP) and smoothed CPP (CPPS) do not require
      exact determination of the cycles of fundamental frequency like established
      perturbation-based measures. They can also be applied to text recordings. In this
      study, they were compared with perceptual evaluation of voice quality and the
      German roughness-breathiness-hoarseness (RBH) scheme. STUDY DESIGN: Retrospective
      data analysis. METHODS: Seventy-three hoarse patients (48.3+/-16.8 years) uttered
      the vowel /e/ and read the German version of the text "The North Wind and the
      Sun". The text recordings were evaluated perceptually by five speech therapists
      and physicians according to the RBH scale. The criterion "overall quality" was
      measured on a 4-point scale and a visual analog scale. For the human-machine
      correlation, the automatic measures of the Praat program (vowels only) and the
      "cpps" software were compared with the experts' ratings. The experiments were
      repeated for speakers with jitter <=5% or shimmer <=5% (n=47). RESULTS: For the
      entire group (n=73), the best human-machine results for most of the rating
      criteria were obtained for text-based CPP and CPPS (up to |rho|=0.73). For the 47
      selected speakers, the correlation was remarkably worse for all measures but
      still best for text-based CPP and CPPS (|rho|<=0.50). CONCLUSIONS: Cepstrum
      analysis should be performed on a text recording. Then, it outperforms all
      perturbation-based measures, and it can be a meaningful objective support for
      perceptual analysis.

PMID- 21940145
TI  - Vocal impact of a prolonged reading task at two intensity levels: objective
      measurements and subjective self-ratings.
AB  - OBJECTIVES: The objectives of this study are to evaluate the impact on voice of
      both duration and intensity level of 2 hours of continuous oral reading. Voice
      modifications accompanying changes in intensity level during prolonged reading
      tasks are analyzed. METHODS: Fifty normophonic women undergo two sessions of
      voice loading in which the required intensity level of voice varied between 60-65
      dB(A) for the first session and 70-75 dB(A) for the second session. The effects
      of loading on objective data (average fundamental frequency [F0], jitter%,
      shimmer%, noise-to-harmonic ratio, maximum phonation time, lowest frequency [F
      Low], highest frequency [F-High], frequency range [Range], lowest intensity [I
      Low] level, and highest intensity level) and self-ratings (voice quality,
      phonation effort, vocal fatigue, and laryngeal discomfort) are assessed every 30
      minutes during the loading tasks. RESULTS: Results indicate that average F0, F
      Low, I-Low, maximum phonation time, feeling of phonation effort, vocal fatigue,
      and laryngeal discomfort increase during prolonged reading, whereas shimmer% and
      self-rating of voice quality decrease. Average F0, F-High, and Range are the only
      parameters influenced by the required intensity of vocal load; they are
      significantly higher in the 70- to 75-dB session compared with the 60- to 65-dB
      session. Concerning the subjective self-ratings, similar results for the four
      ratings used suggest that only one would suffice in future studies. CONCLUSIONS:
      These results confirm the importance of both duration and intensity level as
      loading factors, even if intensity level affects fewer variables than duration.

PMID- 21940146
TI  - Endoscopic laser thyroarytenoid myoneurectomy in patients with adductor spasmodic
      dysphonia: a pilot study on long-term outcome on voice quality.
AB  - OBJECTIVES: Adductor spasmodic dysphonia (ADSD) is a focal laryngeal dystonia,
      which compromises greatly the quality of life of the patients involved. It is a
      severe vocal disorder characterized by spasms of laryngeal muscles during speech,
      producing phonatory breaks, forced, strained and strangled voice. Its symptoms
      result from involuntary and intermittent contractions of thyroarytenoid muscle
      during speech, which causes vocal fold to strain, pressing each vocal fold
      against the other and increasing glottic resistance. Botulinum toxin injection
      remains the gold-standard treatment. However, as injections should be repeated
      periodically leading to voice quality instability, a more definitive procedure
      would be desirable. In this pilot study we report the long-term vocal quality
      results of endoscopic laser thyroarytenoid myoneurectomy. STUDY DESIGN:
      Prospective study. METHODS: Surgery was performed in 15 patients (11 females and
      four males), aged between 29 and 73 years, diagnosed with ADSD. Voice Handicap
      Index (VHI) was obtained before and after surgery (median 31 months
      postoperatively). RESULTS: A significant improvement in VHI was observed after
      surgery, as compared with baseline values (P=0.001). The median and interquartile
      range for preoperative VHI was 99 and 13, respectively and 24 and 42, for
      postoperative VHI. Subjective improvement of voice as assessed by the patients
      showed median improvement of 80%. CONCLUSIONS: Because long-term follow-up showed
      significant improvement of voice quality, this innovative surgical technique
      seems a satisfactory alternative treatment of ADSD patients who seek a definite
      improvement of their condition.

PMID- 21940147
TI  - Comparison of semiquantitative and quantitative assessment of severity of aortic
      regurgitation: clinical implications.
AB  - BACKGROUND: Recent studies have emphasized the importance of quantitative
      assessment of the degree of aortic regurgitation (AR). However, semiquantitative
      methods have remained mainly used despite their unclear diagnostic value. The aim
      of this study was to define the sensitivity and specificity of semiquantitative
      methods compared with the proximal isovelocity surface area method as a reference
      for the diagnostic of severe AR. METHODS: The degree of AR was evaluated using
      the proximal isovelocity surface area method and four semiquantitative
      measurements (left ventricular cardiac output, pressure half-time, diastolic flow
      reversal, and vena contracta) in 224 patients with a wide range of AR severity.
      RESULTS: The mean effective regurgitant orifice area was 25 +/- 14 mm(2) (range,
      3-69 mm(2)), the mean regurgitant volume was 57 +/- 31 mL (range, 9-183 mL), and
      100 patients (44%) had severe AR (effective regurgitant orifice area >= 30 mm(2)
      or regurgitant volume >= 60 mL). Overall, semiquantitative methods had good
      specificity but poor sensitivity, except the vena contracta, which had good
      sensitivity and specificity. Sensitivity, specificity, and positive and negative
      predictive values of the recommended thresholds for severe AR of the four
      semiquantitative methods were 53%, 89%, 77%, and 73% for left ventricular cardiac
      output >= 10 L/min; 12%, 100%, 100%, and 52% for pressure half-time < 200 msec;
      45%, 87%, 79%, and 60% for diastolic flow reversal >= 18 cm/sec; and 81%, 83%,
      78%, and 85% for vena contracta >= 6 mm, respectively. CONCLUSIONS: For the
      assessment of AR severity, current thresholds appear specific but poorly
      sensitive, except for vena contracta, which provides good discriminative value.
      Semiquantitative methods should be integrated into the comprehensive evaluation
      of AR severity, but severe AR should not be excluded only on the basis of
      semiquantitative criteria. These results emphasize the need for the quantitative
      assessment of AR severity.

PMID- 21940148
TI  - Qualitative content of auditory hallucinations and suicidal behavior in
      schizophrenia.

PMID- 21940149
TI  - Acute psychotic sequelae of "bath salts".

PMID- 21940150
TI  - Attenuated virulence of a slow-growing pandrug-resistant Acinetobacter baumannii
      is associated with decreased expression of genes encoding the porins CarO and
      OprD-like.

PMID- 21940151
TI  - Mapping prodromal psychosis: a critical review of neuroimaging studies.
AB  - The onset of schizophrenia is usually preceded by a prodromal phase characterized
      by functional decline and subtle prodromal symptoms, which include attenuated
      psychotic phenomena, cognitive deterioration and a decline in socio-occupational
      function. Preventive interventions during this phase are of great interest
      because of the impressive clinical benefits. However, available
      psychopathological criteria employed to define a high risk state for psychosis
      have low validity and specificity. Consequently there is an urgent need of
      reliable neurocognitive markers linked to the pathophysiological mechanisms that
      underlie schizophrenia. Neuroimaging techniques have rapidly developed into a
      powerful tool in psychiatry as they provide an unprecedented opportunity for the
      investigation of brain structure and function. This review shows that
      neuroimaging studies of the prodromal phases of psychosis have the potentials to
      identify core structural and functional markers of an impending risk to psychosis
      and to clarify the dynamic changes underlying transition to psychosis and to
      address significant correlations between brain structure or function and
      prodromal psychopathology. Additionally, neurochemical methods can address the
      key role played by neurotransmitters such as dopamine and glutamate during the
      psychosis onset. To conclude, multimodal neuroimaging may ultimately clarify the
      neurobiology of the prodromal phases by the integration of functional, structural
      and neurochemical findings.

PMID- 21940152
TI  - The impact of COMT gene polymorphisms on suicidality in treatment resistant major
      depressive disorder--a European multicenter study.
AB  - Many association studies have reported associations between the catechol-O
      methyltransferase (COMT) gene and psychiatric disorders including major
      depression (MDD). The COMT gene has further been associated with suicidal
      behaviour, as well as with treatment response, although with conflicting results.
      In the present study, we further elucidate the impact of COMT in treatment
      response in MDD patients with suicide risk and/or a personal history of suicide
      attempts. Two hundred fifty MDD patients were collected in the context of a
      European multicentre resistant depression study and treated with antidepressants
      at adequate doses for at least 4 weeks. Suicidality was assessed using Mini
      International Neuropsychiatric Interview (MINI) and the Hamilton Rating Scale for
      Depression (HAM-D). Treatment response was defined as HAM-D <= 17 and remission
      as HAM-D <= 7 after 4 weeks of treatment with antidepressants at adequate dose.
      Genotyping was performed for seven SNPs (rs4680, rs2075507, rs737865, rs6269,
      rs4633, rs4818 and rs165599) within the COMT gene. With regard to suicide risk
      and personal history of suicide attempts, neither single marker nor haplotypic
      association was found with any SNP after multiple testing correction. In non
      responders, we found significant single marker and haplotypic association with
      suicide risk, but not in responders. The same holds true for both remitters and
      non-remitters, and when testing for association with a personal history of
      suicide attempts and treatment response phenotypes. In conclusion, we found
      significant association of COMT SNPs with suicide risk in MDD patients not
      responding to antidepressant treatment. Larger well-defined cohorts will be
      required to dissect this further.

PMID- 21940154
TI  - A dietary conjugated linoleic acid treatment that slows renal disease progression
      alters renal cyclooxygenase-2-derived prostanoids in the Han: SPRD-cy rat.
AB  - A mixture of dietary conjugated linoleic acid (CLA) isomers reduces inflammation
      and mitigates disease progression in the Han:SPRD-cy rat model of chronic kidney
      disease. Since cyclooxygenase (COX) activities and prostanoid levels are higher
      in diseased kidneys in this rat, and dietary CLA can inhibit COX2 and prostanoid
      production in other tissues, the effects of dietary CLA were investigated. Kidney
      homogenates from normal and diseased Han:SPRD-cy rats were analyzed for
      prostanoid levels under various conditions: endogenous levels, steady-state
      levels (60-min incubations) and produced by COX isoforms. Thromboxane B(2)
      (TXB(2); TXA(2) metabolite), 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha);
      PGI(2) metabolite) and PGE(2) levels under these conditions were two- to ninefold
      higher in diseased kidneys. Dietary CLA resulted in ~32%-53% lower levels of
      prostanoids produced by total COX and COX2 activities in normal and diseased
      kidneys and partially mitigated alterations in COX2 protein levels associated
      with disease. The COX1 protein and activity were higher in renal disease,
      resulting in increased production of TXB(2) and 6-ketoPGF(1alpha), but not
      PGE(2). Dietary CLA had no effect on COX1, however. Disease resulted in up to
      twofold higher ratios of TXB(2)/6-ketoPGF(1alpha), TXB(2)/PGE(2) and 6
      ketoPGF(1alpha) /PGE(2), and dietary CLA partially mitigated these increases
      under several conditions. Elevated levels of renal membrane associated cytosolic
      phospholipase A(2) in diseased kidneys also were reduced by 50% with CLA feeding.
      The effects of CLA feeding on COX2 protein levels and activity indicate that the
      beneficial effect of dietary CLA in this renal disorder is mediated in part via
      effects on COX2-derived prostanoids.

PMID- 21940155
TI  - Chemopreventive effects of the dietary histone deacetylase inhibitor tributyrin
      alone or in combination with vitamin A during the promotion phase of rat
      hepatocarcinogenesis.
AB  - The chemopreventive effects of tributyrin (TB) and vitamin A (VA), alone or in
      combination, were investigated during the promotion phase of rat
      hepatocarcinogenesis. Compared to diethylnitrosamine control rats, TB and TB+VA
      treated rats, but not VA-treated rats, presented a lower incidence and mean
      number of hepatocyte nodules and a smaller size of persistent preneoplastic
      lesions (pPNLs). In addition, TB and TB+VA-treated rats exhibited a higher
      apoptotic body index in pPNL and remodeling PNL, whereas VA-treated rats
      presented only a higher apoptotic body index in remodeling PNL. None of the
      treatments inhibited cell proliferation in PNL. TB and TB+VA-treated rats, but
      not VA-treated rats, exhibited higher levels of H3K9 acetylation and p21 protein
      expression. TB and VA-treated rats exhibited increased hepatic concentrations of
      butyric acid and retinoids, respectively. Compared to normal rats,
      diethylnitrosamine control animals exhibited lower retinyl palmitate hepatic
      concentrations. All groups had similar expression levels and exhibited similar
      unmethylated CRBP-I promoter region in microdissected pPNL, indicating that
      epigenetic silencing of this gene was not involved in alteration of retinol
      metabolism in early hepatocarcinogenesis. Data support the effectiveness of TB as
      a dietary histone deacetylase inhibitor during the promotion phase of
      hepatocarcinogenesis, which should be considered for chemoprevention combination
      strategies.

PMID- 21940153
TI  - Does cardiovascular phenotype explain the association between diabetes and
      incident heart failure? The Strong Heart Study.
AB  - BACKGROUND AND AIMS: Diabetes remains a predictor of incident heart failure (HF),
      independent of intercurrent myocardial infarction (MI) and concomitant risk
      factors. Initial cardiovascular (CV) characteristics, associated with incident
      heart failure (HF) might explain the association of diabetes with incident HF.
      METHODS AND RESULTS: Participants to the 2nd Strong Heart Study exam, without
      prevalent HF or coronary heart disease, or glomerular filtration rate <30
      mL/min/1.73 m(2), were analyzed (n = 2757, 1777 women, 1278 diabetic). Cox
      regression of incident HF (follow-up 8.91 +/- 2.76 years) included incident MI
      censored as a competing risk event. Acute MI occurred in 96 diabetic (7%) and 84
      non-diabetic participants (6%, p = ns). HF occurred in 156 diabetic (12%) and in
      68 non-diabetic participants (5%; OR = 2.89, p < 0.001). After accounting for
      competing MI and controlling for age, gender, BMI, systolic blood pressure,
      smoking habit, plasma cholesterol, antihypertensive treatment, heart rate,
      fibrinogen and C-reactive protein, incident HF was predicted by greater LV mass
      index, larger left atrium, lower systolic function, greater left atrial systolic
      force and urinary albumin/creatinine excretion. Risk of HF was reduced with more
      rapid LV relaxation and anti-hypertensive therapy. Diabetes increases hazard of
      HF by 66% (0.02 < p < 0.001). The effect of diabetes could be explained by the
      level of HbA1c. CONCLUSIONS: Incident HF occurs more frequently in diabetes,
      independent of intercurrent MI, abnormal LV geometry, subclinical systolic
      dysfunction and indicators of less rapid LV relaxation, and is influenced by poor
      metabolic control. Identification of CV phenotype at high-risk for HF in diabetes
      should be advised.

PMID- 21940156
TI  - The influence of immunosuppressive agents on BK virus risk following kidney
      transplantation, and implications for choice of regimen.
AB  - The increasing incidence of BK-associated nephropathy following kidney
      transplantation has prompted an examination of strategies for risk reduction and
      management through immunosuppression manipulation. Evidence from retrospective
      and prospective studies suggests that BK viruria and viremia, and the need for BK
      virus treatment, are higher with tacrolimus than cyclosporine. Combined therapy
      with tacrolimus and mycophenolic acid may be associated with a particularly
      higher risk of BK infection, but data are conflicting as to whether mycophenolic
      acid per se is an independent risk factor. The incidence of BK-related events may
      be reduced in patients receiving mTOR inhibitors (everolimus or sirolimus) with
      cyclosporine vs a calcineurin inhibitor with mycophenolic acid. De novo
      immunosuppression regimens that avoid rabbit antithymocyte globulin and
      tacrolimus, particularly tacrolimus with mycophenolic acid, may be advantageous,
      whereas low-exposure cyclosporine with an mTOR inhibitor appears a favorable
      option. Routine screening for BK infection during the first 2 years
      posttransplant is recommended to allow preemptive modification of the
      immunosuppressive regimen. In patients at high risk of BK virus infection,
      appropriate de novo immunosuppression or very early conversion to an mTOR
      inhibitor to facilitate reduction or discontinuation of calcineurin inhibitors or
      antimetabolites should be considered. Extensive further research into optimal
      avoidance, screening, and treatment strategies is required.

PMID- 21940157
TI  - Life-cycle assessment of a waste refinery process for enzymatic treatment of
      municipal solid waste.
AB  - Decrease of fossil fuel dependence and resource saving has become increasingly
      important in recent years. From this perspective, higher recycling rates for
      valuable materials (e.g. metals) as well as energy recovery from waste streams
      could play a significant role substituting for virgin material production and
      saving fossil resources. This is especially important with respect to residual
      waste (i.e. the remains after source-separation and separate collection) which in
      Denmark is typically incinerated. In this paper, a life-cycle assessment and
      energy balance of a pilot-scale waste refinery for the enzymatic treatment of
      municipal solid waste (MSW) is presented. The refinery produced a liquid
      (liquefied organic materials and paper) and a solid fraction (non-degradable
      materials) from the initial waste. A number of scenarios for the energy
      utilization of the two outputs were assessed. Co-combustion in existing power
      plants and utilization of the liquid fraction for biogas production were
      concluded to be the most favourable options with respect to their environmental
      impacts (particularly global warming) and energy performance. The optimization of
      the energy and environmental performance of the waste refinery was mainly
      associated with the opportunity to decrease energy and enzyme consumption.

PMID- 21940158
TI  - A one-step electrochemical method for DNA detection that utilizes a peroxidase
      mimicking DNAzyme amplified through PCR of target DNA.
AB  - A novel one-step electrochemical method for DNA detection is described. The
      procedure utilizes a reaction catalyzed by a peroxidase-mimicking DNAzyme to
      produce a product, which forms an insoluble precipitation layer on the surface of
      an electrode. A rationally designed forward primer, conjugated with a peroxidase
      DNAzyme complementary sequence at its 5'-end, is used for PCR amplification of
      target DNA. As a result, the DNAzyme sequence is produced by amplification only
      when the target DNA is present in the sample. The PCR product is then subjected
      to the precipitation reaction on the electrode surface using an electrolyte assay
      buffer containing 4-chloronaphthol, hydrogen peroxide, ferrocenemethanol, hemin,
      and 5'-lambdaexonuclease. Finally, analysis is carried out using Faradaic
      impedance spectroscopy. The impedance value was found to greatly increase when
      target DNA is present owing to the formation of a precipitation layer on the
      electrode surface caused by the catalytic action of the DNAzyme. In contrast, no
      impedance increase is observed when a control sample not containing target DNA is
      utilized. By employing this strategy, target DNA from Chlamydia trachomatis was
      reliably detected within a 10 min period following precipitation without the need
      for complicated secondary procedures. This effort has led to the development of a
      highly convenient electrochemical one-step method for DNA detection that utilizes
      a peroxidase-mimicking DNAzyme, which is specifically designed to undergo
      amplification during PCR of target DNA.

PMID- 21940159
TI  - Volumetric modulated arc radiotherapy for esophageal cancer.
AB  - A treatment planning study was performed to evaluate the performance of
      volumetric arc modulation with RapidArc (RA) against 3D conformal radiation
      therapy (3D-CRT) and conventional intensity-modulated radiation therapy (IMRT)
      techniques for esophageal cancer. Computed tomgraphy scans of 10 patients were
      included in the study. 3D-CRT, 4-field IMRT, and single-arc and double-arc RA
      plans were generated with the aim to spare organs at risk (OAR) and healthy
      tissue while enforcing highly conformal target coverage. The planning objective
      was to deliver 54 Gy to the planning target volume (PTV) in 30 fractions. Plans
      were evaluated based on target conformity and dose-volume histograms of organs at
      risk (lung, spinal cord, and heart). The monitor unit (MU) and treatment delivery
      time were also evaluated to measure the treatment efficiency. The IMRT plan
      improves target conformity and spares OAR when compared with 3D-CRT. Target
      conformity improved with RA plans compared with IMRT. The mean lung dose was
      similar in all techniques. However, RA plans showed a reduction in the volume of
      the lung irradiated at V(20Gy) and V(30Gy) dose levels (range, 4.62-17.98%)
      compared with IMRT plans. The mean dose and D(35%) of heart for the RA plans were
      better than the IMRT by 0.5-5.8%. Mean V(10Gy) and integral dose to healthy
      tissue were almost similar in all techniques. But RA plans resulted in a reduced
      low-level dose bath (15-20 Gy) in the range of 14-16% compared with IMRT plans.
      The average MU needed to deliver the prescribed dose by RA technique was reduced
      by 20-25% compared with IMRT technique. The preliminary study on RA for
      esophageal cancers showed improvements in sparing OAR and healthy tissue with
      reduced beam-on time, whereas only double-arc RA offered improved target coverage
      compared with IMRT and 3D-CRT plans.

PMID- 21940161
TI  - Heterogeneous catalytic reduction of anthropogenic pollutant, 4-nitrophenol by
      silver-bionanocomposite using Cylindrocladium floridanum.
AB  - In the present investigation, the silver-bionanocomposite with fcc structured Ag
      nanocrystals was synthesized using the fungus, Cylindrocladium floridanum through
      a novel, environmentally benign biological process. Silver-bionanocomposite was
      systematically characterized by UV-Vis spectroscopy, XRD, SEM, EDX, and TEM
      techniques. TEM analysis of mycelia confirmed the presence of silver
      nanoparticles (AgNPs) on the outer surface of the cell wall and inner of
      cytoplasmic membrane of the fungus, when cultured in aqueous solution of AgNO3 at
      30  degrees C for a period of 7 days in static condition. Additionally, it was
      observed that bionanocomposite with AgNPs functions as an efficient heterogeneous
      catalyst in the degradation of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP), in
      the presence of reducing agent, sodium borohydride which was reflected by UV-Vis
      spectra of the catalytic reaction kinetics. This is the first report of the
      silver-bionanocomposite using fungus, Cy. floridanum, heterogeneously catalyzing
      the reduction of a toxic pollutant, 4-NP to 4-AP.

PMID- 21940162
TI  - Copper reduction in a pilot-scale membrane-free bioelectrochemical reactor.
AB  - A pilot-scale, membrane-free, bioelectrochemical system (BES) reactor (16L in
      volume) installed by five cathodes with different distance to anode was tested
      for the removal of copper. CuSO4 solution was used as catholyte and anaerobic
      microorganisms grew as anodic biocatalyst. In the reactor, Cu(II) was reduced and
      recovered as solid-state copper deposits on cathodes accompanied with power
      production. When 600 and 2000 mg of Cu2+ were added into the cathode chamber,
      removal efficiency of 92% over 480 h and 48% over 672 h period with electric
      quantities of 2724 C and 8703 C, and cathodic efficiencies of 61.92% and 45.60%
      were achieved, respectively. The reduction reaction rate depended on the initial
      average Cu2+ concentration. The internal resistance decreased and voltage output
      increased as the distance of each cathode to anode decreased. The mass of metal
      Cu crystals and Cu(I) compounds deposited on each cathode was dependent on
      current intensity.

PMID- 21940163
TI  - Effects of soybean curd wastewater on the growth and hydrocarbon production of
      Botryococcus braunii strain BOT-22.
AB  - A laboratory study was conducted to evaluate the possibility of using wastewater
      from a soybean curd manufacturing plant as a growth promoter of Botryococcus
      braunii strain BOT-22. Soybean curd wastewater (SCW) were added to AF-6 medium to
      set the final concentration to 0% (control), 1%, 2%, 5%, and 10% (v/v). The
      growth and hydrocarbon production observed in the cultures with 1% and 2% SCW
      were significantly higher than that observed in the control. It was postulated
      that proteins and/or reducing sugars in SCW could enhance the growth. A major
      finding was a shift in the chemical composition of hydrocarbons from C(34)H(58)
      to C(32)H(54) in association with increased concentrations of SCW. Considering
      the inorganic ions in SCW, it was presumed that a mixture of nitrate, 1-2% SCW,
      and secondarily treated SCW can be applied for mass cultivation of Botryococcus.

PMID- 21940164
TI  - Quantitative evaluation of heavy metals' pollution hazards in liquefaction
      residues of sewage sludge.
AB  - Liquefaction residues (LR) are the main by-products of sewage sludge (SS)
      liquefaction. This study quantitatively evaluates the potential ecological risk
      and pollution degrees of heavy metals (Pb, Zn, Cu, Cd, Cr and Ni) in LR versus
      SS. The leaching rates (R1) of heavy metals in LR were much lower than those in
      SS, revealing that the mobility/leachability of heavy metals was well suppressed
      after liquefaction. Geo-accumulation index (Igeo) indicated that the liquefaction
      process significantly weakened the contamination degrees of heavy metals.
      Potential ecological risk index (RI) demonstrated that overall risks caused by
      heavy metals were obviously lowered from 1093.56 (very high risk) in SS to 4.72
      and 1.51 (low risk) in LR1 and LR2, respectively. According to the risk
      assessment code (RAC), each tested heavy metal had no or low risk to the
      environments after liquefaction. In a word, the pollution hazards of heavy metals
      in LR were markedly mitigated.

PMID- 21940165
TI  - Upgrading activated sludge systems and reduction in excess sludge.
AB  - Most of 200 Activated Sludge Plant in Iran are overloaded and as a result, their
      efficiency is low. In this work, a pilot plant is manufactured and put into
      operation in one of the wastewater treatment plants in the west of Tehran.
      Instead of conventional activated sludge, a membrane bioreactor and an upflow
      anaerobic sludge blanket reactor used as a pretreatment unit in this pilot. For
      the sake of data accuracy and precision, an enriched municipal wastewater was
      opted as an influent to the pilot. Based on the attained result, the optimum
      retention time in this system was 4h, and the overall COD removal efficiency was
      98%. As a whole, the application of this retrofit would increase the plant's
      capacity by a factor of 5 and reducing the excess sludge by a factor of 10. The
      sludge volume index in the anaerobic reactor was about 12 after granulation
      occurred.

PMID- 21940166
TI  - Chemical scaffolds with structural similarities to siderophores of nonribosomal
      peptide-polyketide origin as novel antimicrobials against Mycobacterium
      tuberculosis and Yersinia pestis.
AB  - Mycobacterium tuberculosis (Mtb) and Yersinia pestis (Yp) produce siderophores
      with scaffolds of nonribosomal peptide-polyketide origin. Compounds with
      structural similarities to these siderophores were synthesized and evaluated as
      antimicrobials against Mtb and Yp under iron-limiting conditions mimicking the
      iron scarcity these pathogens encounter in the host and under standard iron-rich
      conditions. Several new antimicrobials were identified, including some with
      increased potency in the iron-limiting condition. Our study illustrates the
      possibility of screening compound libraries in both iron-rich and iron-limiting
      conditions to identify antimicrobials that may selectively target iron scarcity
      adapted bacteria and highlights the usefulness of building combinatorial
      libraries of compounds having scaffolds with structural similarities to
      siderophores to feed into antimicrobial screening programs.

PMID- 21940167
TI  - Design and synthesis of a library of chemokine antagonists.
AB  - A library of chemokine antagonists has been synthesized using a combination of
      solid and solution-phase chemistry. Structures of known chemokine antagonists
      were used to produce a pharmacophore which served to guide monomer selection.
      Several combinations of monomers have resulted in providing novel chemokine
      antagonists which in some cases display dual chemokine receptor antagonism.

PMID- 21940168
TI  - Cell fingerprint patterns using designed alpha-helical peptides to screen for
      cell-specific toxicity.
AB  - We conducted cell-based cytotoxicity screening of a 101-membered alpha-helical
      peptide library using cell fingerprints (CFPs). The CFP data suggested that there
      is a relationship between cytotoxicity and peptide characteristics, such as
      hydrophobicity, charge, and amino acid composition. In spite of the small size of
      the library used in this study, several peptides demonstrated cell-specific
      toxicity. The strategy of combining a designed peptide library with CFP thus
      shows real promise for peptide-based screening with cells.

PMID- 21940169
TI  - Homo- and hetero-dimers of inactive organophosphorous group binding at dual sites
      of AChE.
AB  - Homo- and hetero-dimers of inactive organophosphorous group(s) dramatically
      enhanced the acetylcholinesterase (AChE; EC 3.1.1.7) inhibiting potency, with the
      highest potency observed at a tether length of 6 methylene groups (6d) for the
      homodimers, and 7 methylene groups (8e) for the heterodimers. The docking model
      of Drosophila melanogaster AChE suggested that 6d and 8e bound at the catalytic
      and peripheral sites of AChE, in which two organophosphorous groups of 6d
      individually oriented towards TRP83 of catalytic sites and TRP321 of peripheral
      sites, and phthalicimide group of 8e was appropriately arranged for a pi-pi
      interaction with the phenyl ring of TYR330, furthermore, the organophosphorous
      group introduced hydrophobic interaction with TRP83. The compounds prepared in
      this work demonstrated high insecticidal activity to Lipaphis erysimi and
      Tetranychus cinnbarinus at the concentration 300mg/L.

PMID- 21940170
TI  - Clinical features in a series of fast channel congenital myasthenia syndrome.
AB  - Fast channel congenital myasthenic syndromes are rare, but frequently result in
      severe weakness. We report a case of 12 fast channel patients to highlight
      clinical features and management difficulties. Patients were diagnosed through
      genetic screening and identification of mutations shown to cause fast channel
      syndrome. Data was obtained from clinical notes, history, examination and follow
      up. Patterns of muscle weakness involved limb, trunk, bulbar, respiratory, facial
      and extraocular muscles. Patients responded to treatment with anticholinesterase
      medication and 3,4-diaminopyridine. Fast channel syndrome contrasted with AChR
      deficiency in the occurrence of severe respiratory crises in infancy and
      childhood. The death of two children even when on treatment and the family
      histories of sibling deaths re-inforces the need for accurate genetic diagnosis,
      optimised pharmacological treatment and additional supportive measures to manage
      acute respiratory crises. Referral to a specialist paediatric respiratory centre
      and regular resuscitation training for parents are recommended.

PMID- 21940171
TI  - A novel MPZ mutation in Charcot-Marie-Tooth disease type 1B with focally folded
      myelin and multiple entrapment neuropathies.
AB  - Charcot-Marie-Tooth type 1B (CMT1B) is a demyelinating neuropathy caused by
      mutations in the myelin protein zero (MPZ) gene. Here, we describe a patient with
      CMT1B with focally folded myelin, a rarely reported phenotype of CMT1B, who
      initially presented with multiple entrapment neuropathies. She complained of
      palmar dysesthesia on both sides and on both soles of her feet in her 30's. She
      underwent bilateral carpal and tarsal tunnel release at age 44, which provided
      transient relief from the symptoms. A sural nerve biopsy performed at age 49
      revealed focally folded myelin. Molecular genetic analysis revealed a novel
      Asn131Ser mutation in MPZ.

PMID- 21940172
TI  - Gait assessment in mild cognitive impairment and Alzheimer's disease: the effect
      of dual-task challenges across the cognitive spectrum.
AB  - Gait impairment is a prominent falls risk factor and a prevalent feature among
      older adults with cognitive impairment. However, there is a lack of comparative
      studies on gait performance and fall risk covering the continuum from normal
      cognition through mild cognitive impairment (MCI) to Alzheimer's disease (AD). We
      evaluated gait performance and the response to dual-task challenges in older
      adults with AD, MCI and normal cognition without a history of falls. We
      hypothesized that, in older people without history of falls, gait performance
      will deteriorate across the cognitive spectrum with changes being more evident
      under dual-tasking. Gait was assessed using an electronic walkway under single
      and three dual-tasks conditions. Gait velocity and stride time variability were
      not significantly different between the three groups under the single-task
      condition. By contrast, significant differences of decreasing velocity
      (p<0.0001), increasing stride time (p=0.0057) and increasing stride time
      variability (p=0.0037) were found under dual-task testing for people with MCI and
      AD. Less automatic and more complex dual-task tests, such as naming animals and
      serial subtraction by sevens from 100, created the greatest deterioration of gait
      performance. Gait changes under dual-tasking for the MCI and AD groups were
      statistically different from the cognitively normal controls. Dual-task
      assessment exposed gait impairments not obvious under a single-task test
      condition and may facilitate falls risk identification in cognitively impaired
      persons without a history of falls.

PMID- 21940173
TI  - Aminomethyltetrazoles as potential inhibitors of the gamma-aminobutyric acid
      transporters mGAT1-mGAT4: synthesis and biological evaluation.
AB  - 1,5-Disubstituted and 5-monosubstituted aminomethyltetrazole derivatives derived
      from glycine were synthesized employing a TMSN(3)-modified variant of the Ugi
      reaction as a key step. All compounds were evaluated regarding their inhibitory
      potency and subtype selectivity at the four murine GABA transporter subtypes
      mGAT1-mGAT4. Though none of the 5-monosubstituted tetrazoles turned out to
      inhibit [(3)H]GABA uptake to a significant extent, the 1,5-disubstituted
      tetrazole derivatives displayed a distinct activity, especially at the GABA
      transport proteins mGAT2-mGAT4. Thus, a reasonable potent and selective inhibitor
      of mGAT3 was found. Additionally, two more compounds were identified as potent
      inhibitors of mGAT2. This is especially relevant, as up to date only few potent
      inhibitors of mGAT2 that do not affect mGAT1 are known.

PMID- 21940174
TI  - A sucrose-derived scaffold for multimerization of bioactive peptides.
AB  - A spherical molecular scaffold bearing eight terminal alkyne groups was
      synthesized in one step from sucrose. One or more copies of a tetrapeptide azide,
      either N(3)(CH(2))(5)(CO)-His-DPhe-Arg-Trp-NH(2) (MSH4) or N(3)(CH(2))(5)(CO)-Trp
      Met-Asp-Phe-NH(2) (CCK4), were attached to the scaffold via the copper(I)
      catalyzed azide-alkyne cycloaddition (CuAAC) reaction. Competitive binding assays
      using Eu-labeled probes based on the superpotent ligands Ser-Tyr-Ser-Nle-Glu-His
      DPhe-Arg-Trp-Gly-Lys-Pro-Val-NH(2) (NDP-alpha-MSH) and Asp-Tyr-Met-Gly-Trp-Met
      Asp-Phe-NH(2) (CCK8) were used to study the interactions of monovalent and
      multivalent MSH4 and CCK4 constructs with Hek293 cells engineered to overexpress
      MC4R and CCK2R. All of the monovalent and multivalent MSH4 constructs exhibited
      binding comparable to that of the parental ligand, suggesting that either the
      ligand spacing was inappropriate for multivalent binding, or MSH4 is too weak a
      binder for a second 'anchoring' binding event to occur before the monovalently
      bound construct is released from the cell surface. In contrast with this
      behavior, monovalent CCK4 constructs were significantly less potent than the
      parental ligand, while multivalent CCK4 constructs were as or more potent than
      the parental ligand. These results are suggestive of multivalent binding, which
      may be due to increased residence times for monovalently bound CCK4 constructs on
      the cell surface relative to MSH4 constructs, the greater residence time being
      necessary for the establishment of multivalent binding.

PMID- 21940175
TI  - Synthesis and evaluation of novel macrocyclic antifungal peptides.
AB  - Echinocandins are a novel class of macrocyclic antifungal peptides that act by
      inhibiting the beta-(1,3)-D-glucan synthase complex, which is not present in
      mammalian cells. Due to the large number of hydroxyl groups present in these
      complex macrocyclic lipopeptides, most structure-activity relationship studies
      have relied upon semisynthetic derivatives. In order to probe the influence of
      the cyclic peptide backbone on the antifungal activity we developed a successful
      strategy for the synthesis of novel echinocandins analogues by on-resin ring
      closing metathesis or disulfide formation. The specific minimum inhibitory
      activity of each mimic was determined against Candida albicans. Our results
      indicate that ring size is an important factor for antifungal activity.

PMID- 21940176
TI  - FTIR and circular dichroism spectroscopic study of interaction of 5-fluorouracil
      with DNA.
AB  - 5-Fluorouracil (5FU) is an anticancer chemotherapeutic drug which exerts
      cytotoxic effect by inhibiting cellular DNA replication. In the present study, we
      explore the binding of 5FU with DNA and resulting structural and conformational
      changes on DNA duplex. UV-visible, Fourier transform infrared (FTIR) and circular
      dichroism (CD) spectroscopic techniques were employed to explore these
      interactions. A constant concentration of calf thymus DNA was incubated with
      varying concentrations of 5FU. UV-visible and FTIR spectroscopic results revealed
      that intercalation is the primary mode of interaction between 5FU and nitrogenous
      bases of the nucleic acid. The binding constant was found to be 9.7*10(4); which
      is indicative of moderate type of interaction between 5FU and DNA duplex. It was
      also observed that 5FU intercalates slightly more between AT base pairs compared
      to GC pairs. FTIR and circular dichroism spectroscopic results revealed that 5FU
      disturbs native B-conformation of DNA though, DNA remains in its B conformation
      even at higher concentrations of 5FU.

PMID- 21940177
TI  - Early inflammation in the absence of overt infection in preterm neonates exposed
      to intensive care.
AB  - BACKGROUND: Systemic inflammation, typically attributed to sepsis, has been
      repeatedly linked to adverse long-term outcomes in infants born prematurely.
      However, it is unclear whether other factors can contribute to potentially
      harmful systemic inflammatory responses. OBJECTIVE: To determine the timing and
      extent of systemic inflammation occurring in absence of infection in preterm
      infants exposed to intensive care. METHODS: First, we screened for inflammation
      biomarkers most strongly linked to infection in a large prospective cohort of 425
      newborns (gestational age 24-42 weeks). Second, we longitudinally measured levels
      of infection-related inflammation biomarkers up to 42 days of post-natal life in
      a series of 58 infants born <=30 weeks of gestation exposed to intensive care.
      Ante- or post-natal infections were excluded using stringent definitions
      including rigorous histological placental examination. Spearman correlations were
      used to identify putative clinical factors potentially linked to inflammation.
      RESULTS: Three biomarkers were most strongly associated with neonatal sepsis (IL
      6, IL-8 and G-CSF) in the first cohort. Using these markers, we found a
      predominant early high intensity systemic inflammation period within the first 72
      h of preterm infants' extra-uterine life. Remarkably, this systemic inflammatory
      response was of magnitude comparable to that observed during sepsis in absence of
      ante- or post-natal signs of infection, and correlated with the amount of
      supplemental oxygen exposure (r=0.51-0.60). CONCLUSIONS: Non-infectious sources
      of systemic inflammation are significant in preterm infants exposed to intensive
      care and may contribute to intensive care-related organ injury.

PMID- 21940178
TI  - Monitoring serum levels ELR+ CXC chemokines and the relationship between
      microvessel density and angiogenic growth factors in multiple myeloma.
AB  - BACKGROUND: The ELR+ CXC chemokines are important mediators of tumorigenesis,
      related to their angiogenic properties. Angiogenesis appears to be a prominent
      feature in the progression of multiple myeloma (MM). CXC chemokines have four
      highly conserved cysteine amino acid residues, with the first two cysteine
      molecules separated by a single amino acid. The angiogenic potential of this
      group is determined by the presence of three amino acid residues (Glu-Leu-Arg:
      the ELR motif) preceding the first cysteine amino acid, in the NH2 terminus.
      AIMS: The purpose of this study was to determine serum concentrations of
      angiogenesis-related chemokines ELR+ motif, such as interleukin-8 (IL-8),
      epithelial neutrophil activating protein-78 (ENA-78) and growth-related gene
      alpha (GRO-alpha), as well the bone marrow microvascular density (MVD) in
      patients with MM at diagnosis and after treatment, in plateau phase. We also
      evaluated the relationship among them with other known growth factors involved in
      angiogenesis. METHODS: Serum levels of the ELR+ CXC chemokines: IL-8, ENA-78 and
      GRO-alpha as well as of the angiogenic factors: hepatocyte growth factor (HGF),
      vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha (TNF
      alpha) were determined in 63 newly diagnosed MM patients, in 30 in plateau phase
      and in 20 healthy controls. Serum measurements of them were performed with
      commercially available kits for ELISA. Bone marrow biopsies were performed before
      and after treatment, in plateau phase, in order to determine MVD by staining
      vessels with anti-CD31. RESULTS: Serum concentrations of IL-8, ENA-78, GRO-alpha
      and TNF-alpha were significantly higher in the group of MM patients (44.5+/-25.3,
      765+/-572.1, 186.5+/-129.1 and 4.2+/-2.8 pg/ml, respectively) in comparison to
      control group (27.3+/-6.4, 335.1+/-268.6, 112.5+/-76.1 and 1.3+/-0.8 pg/ml)
      (p<0.02 for GRO-alpha, p<0.001 for other cases). We also found that untreated
      patients had higher levels of IL-8, ENA-78, GRO-alpha than post treatment
      patients, but statistical significant difference was found only for IL-8 (48.36+/
      30.93 pg/ml vs. 35.05+/-19.77 pg/ml, p<0.001). Furthermore IL-8, GRO-alpha, TNF
      alpha, HGF and VEGF were significantly higher with increasing disease stage
      (p<0.001 in all cases). ENA-78 serum levels were higher in stage III than in
      stage I and II, but without statistical significance. Additionally we correlated
      each proinflammatory cytokine with well known angiogenic factors such as HGF,
      VEGF and TNF-alpha. A positive correlation was found between serum HGF and IL-8
      and GRO-alpha (r=0.316 p<0.01, r=0.297 p<0.02, respectively). Similarly serum
      VEGF correlated with ENA-78 and GRO-alpha (r=0.323 p<0.01, r=0.469 p<0.001,
      respectively). In the pretreatment group of patients a positive correlation
      between bone marrow MVD and serum levels of GRO-alpha was found (r=0.304 p<0.01).
      There was a difference in survival times between patients with higher than median
      versus low IL-8, ENA-78 and GRO-alpha levels, but the differences could not reach
      statistical significance in either case. CONCLUSIONS: These findings support the
      hypothesis that ELR+ motif CXC chemokines, such as IL-8, ENA-78 and GRO-alpha
      correlate with angiogenic growth factors and may play a role in the progression
      of MM. Further studies are needed to determine their prognostic and predictive
      significance.

PMID- 21940180
TI  - What is the impact of nutritional status on health-related quality of life in
      hemodialysis patients?
AB  - OBJECTIVES: To develop a nutrition-specific quality of life (NSQOL) questionnaire
      that combines the Appetite and Diet Assessment Tool and the Food Enjoyment in
      Dialysis tool, and to measure the association between nutritional status and both
      the NSQOL and the generic health-related quality of life (HRQOL) in hemodialysis
      patients. METHODS: Cross-sectional study of 89 hemodialysis patients. Nutritional
      status was measured by subjective global assessment and biochemical indices,
      including serum albumin concentration. Adequacy of dialysis was also measured. To
      determine the correlation between quality of life and nutritional status, both
      the NSQOL and the HRQOL instruments were used. RESULTS: The mean NSQOL score for
      the entire cohort was 8.9 +/- 4.5. The NSQOL was positively correlated with the
      mental component score (r = 0.52, P < .001) and the physical component score
      (PCS) (r = 0.29, P < .05) of the HRQOL questionnaire. There was no difference in
      the NSQOL score between the moderately malnourished and the mildly malnourished
      to well-nourished patients. The mean PCS was significantly lower in the
      moderately malnourished group as compared with the mildly malnourished and well
      nourished groups (33.4 +/- 10.7 vs. 38.9 +/- 10.2, P < .05); however, there was
      no difference in the mean mental component score between the groups. Nutritional
      status, as assessed by subjective global assessment, was positively correlated
      with the PCS (r = 0.33, P < .05) and serum albumin concentration (r = 0.35, P =
      .01). CONCLUSION: We developed an NSQOL questionnaire by combining the Appetite
      and Diet Assessment Tool and the Food Enjoyment in Dialysis tool. The NSQOL
      questionnaire is a rapid self-administered tool that can be used to assess
      appetite-related quality of life in patients receiving maintenance hemodialysis.
      This instrument correlated well with HRQOL indices in this cohort of hemodialysis
      patients.

PMID- 21940181
TI  - Painless giant angioleiomyoma in the subfascia of the lower leg.
AB  - Angioleiomyoma is rare, benign vascular smooth muscle tumor originating from the
      tunica media of the veins and arteries. It usually presents as a slow-growing,
      small, and painful mass arising from the cutaneous or subcutaneous tissue. We
      report an unusual case of angioleiomyoma that was located in the subfascia of the
      lower leg and had grown to massive size (<=5 cm in diameter) during a 3-year
      period without pain. A 57-year-old female presented with a 3-year history of a
      slowly growing pain-free mass on the anterior portion of her right lower leg,
      just above the ankle joint. Magnetic resonance imaging revealed a well-demarcated
      lesion, measuring approximately 5 * 4 cm, located deep to the fascia of the
      anterior compartment of the lower leg and adjacent to the tibia, fibula, and
      interosseous membrane. The mass was isointense to skeletal muscle on T(1)
      weighted images, hyperintense and heterogeneous on T(2)-weighted images, and
      enhanced intensely and heterogeneously after the intravenous administration of
      contrast medium. We performed an excision, and histologic analysis revealed
      smooth muscle cells surrounding blood vessels of various sizes. From these
      histologic findings, the tumor was diagnosed as a solid form of angioleiomyoma.
      The present case was unique in that the tumor grew to a massive size without pain
      and was located deep to the fascia.

PMID- 21940179
TI  - Treatment options and strategies for antibody mediated rejection after renal
      transplantation.
AB  - Antibody mediated rejection is a significant clinical problem encountered in a
      subset of renal transplant recipients. This type of rejection has a variable
      pathogenesis from the presence of donor specific antibodies with no overt disease
      to immediate hyperacute rejection and many variations between. Antibody mediated
      rejection is more common in human leukocyte antigen sensitized patients. In
      general, transplant graft survival after antibody mediated rejection is
      jeopardized, with less than 50% graft survival 5 years after this diagnosis. A
      variety of agents have been utilized singly and in combinations to treat antibody
      mediated rejection with differing results and significant research efforts are
      being placed on developing new targets for intervention. These same agents have
      been used in desensitization protocols with some success. In this review, we
      describe the biology of antibody mediated rejection, review the available agents
      to treat this form of rejection, and highlight areas of ongoing and future
      research into this difficult clinical problem.

PMID- 21940182
TI  - Canine periodontitis: the dog as an important model for periodontal studies.
AB  - Periodontal disease (PD) refers to a group of inflammatory diseases caused by
      bacterial plaque in the periodontium and ranges from an early stage (gingivitis)
      to an advanced stage (periodontitis). It is a multifactorial disease that results
      from the interaction of the host defence mechanisms with the plaque
      microorganisms. Early detection, diagnosis and treatment are essential in the
      control of this disease. PD has an enormous impact on human and veterinary
      medicine due to its high prevalence. The most common animal PD models use dogs
      and non-human primates, although other animals (rats, mice, hamsters, rabbits,
      miniature pigs, ferrets, and sheep) have also been employed. Dog models have
      contributed significantly to the current understanding of periodontology. The
      most important clinical aspects of canine PD are considered in this review and
      the various animal models are examined with an emphasis on the role of the dog as
      the most useful approach for understanding human PD and in the development of new
      therapeutic and preventive measures.

PMID- 21940183
TI  - Arm and hand function in children with unilateral cerebral palsy: a one-year
      follow-up study.
AB  - BACKGROUND: In children with unilateral cerebral palsy (CP), development of arm
      and hand function is often compromised by the underlying motor and sensory
      impairments. However, knowledge about the evolution of arm and hand function in
      this population is limited. AIM: The aims were to map the evolution of scores on
      upper limb measures over one year in children with unilateral CP and to identify
      factors that influence time trends. METHODS: Eighty-one children (43 males, 38
      females; mean age 9y11mo (SD 3y3mo) range 5-15 y) were tested at baseline, at 6
      and 12 months. According to the International Classification of Functioning,
      Disability and Health, body function measurements included passive range of
      motion, muscle tone, manual muscle strength and grip strength. Activity
      measurements included the Melbourne Assessment, the Jebsen-Taylor test, the
      Assisting Hand Assessment and the Abilhand-Kids questionnaire. Age, gender,
      etiology (congenital or acquired lesions) and Manual Ability Classification
      System (MACS) levels were analyzed as predictive factors, using mixed models.
      RESULTS: Scores for grip strength (p = 0.001) and manual dexterity (Jebsen-Taylor
      test, p < 0.0001) increased significantly over time. MACS level (p = 0.03) and
      etiology (p = 0.02) had a significant influence on the time evolution of the
      Jebsen-Taylor scores. Other assessments showed no significant changes.
      CONCLUSION: Motor impairments, movement quality and hemiplegic hand use in
      bimanual tasks do not spontaneously improve over one year, except for an age
      related change in grip strength. However, an improvement was observed in manual
      dexterity, suggesting that some children can learn more adaptive movement
      strategies.

PMID- 21940184
TI  - A diagnostic algorithm for the evaluation of early onset genetic-metabolic
      epileptic encephalopathies.
AB  - Early onset epileptic encephalopathies represent a struggling challenge in
      neurological clinical practice, mostly in infants and very young children, partly
      due to an unclear and still debated cathegorization. In this scenario genetic and
      metabolic epileptic encephalopathies play a central role, with new entries still
      needing an arrangement. In this Paper we present a brief overview on genes,
      metabolic disorders and syndromes picturing the pathogenesis of genetic and
      metabolic epileptic encephalopathies with onset under one year of age. These
      forms will be classified, according to a combined clinical and genetic-metabolic
      criterion, into two main groups including seizures as prominent/unique symptom
      and seizures associated with a syndromic phenotype. Starting from this
      classification we suggest a possible simplified diagnostic algorithm, discussing
      main decision making nodes in practical patients management. The aim of the
      proposed algorithm is to guide through metabolic and molecular-genetic work up
      and to clarify "where" and "what" to search in biochemical,
      electroencephalographic and neuroimaging investigations.

PMID- 21940185
TI  - A multi-frequency EPR spectroscopy approach in the detection of boson peak
      excitations.
AB  - The influence of boson peak (BP) excitations on low-temperature spin-lattice
      relaxation rate of a paramagnetic center embedded in a glassy matrix is
      investigated in the context of multi-frequency electron paramagnetic resonance
      (EPR) detection. In the theoretical analysis, the transition rate of spin one
      half in the presence of a phonon field is calculated within the approximation of
      Fermi's golden rule. Several phonon densities of states are compared, among which
      one originating from a model of quasi-localized vibrations has been introduced
      into electron spin relaxation formalism for the first time. The respective
      frequency dependencies of spin-lattice relaxation rates are predicted which
      should lead to observable effects of BP modes if a multi-frequency study at very
      low temperatures is performed.

PMID- 21940186
TI  - Protein-ligand docking guided by ligand pharmacophore-mapping experiment by NMR.
AB  - We developed a new protein-ligand docking calculation method using experimental
      NMR data. Recently, we proposed a novel ligand epitope-mapping experiment, which
      utilizes the difference between the longitudinal relaxation rates of ligand
      protons with and without irradiation of target protein protons (DIRECTION epitope
      mapping experiment; Y. Mizukoshi, et al., An accurate pharmacophore mapping
      method by NMR, submitted for publication). Although the epitope-mapping
      experiment is simple and rapid, the result should reflect the proximity of ligand
      protons to the target protein surface. However, it cannot directly provide the
      protein-ligand complex structure without any other structural information. While
      the accuracy of protein-ligand docking software is insufficient, the software can
      provide many candidate complex structures. In many cases, the correct complex
      structure is included in the set of predicted complex structures and the correct
      structures could be selected by applying the above experimental result of ligand
      epitope mapping. In the current study, we combined the protein-ligand docking
      software with the NMR experimental information so as to improve the prediction of
      the protein-ligand complex structure. Consequently, the prediction accuracy was
      improved by 1.3-1.9 times (from ca. 50% to ca. 70%) in a self-docking test for
      the simulated epitope mapping result. Moreover, this method was applied to actual
      NMR experiments, and it successfully reconstructed the protein-ligand complex
      structures.

PMID- 21940187
TI  - Measurement of temperature changes in cooling dead rats using magnetic resonance
      thermometry.
AB  - Magnetic resonance imaging thermometry has been introduced as a technique for
      measurement of temperature changes in cooling dead rats. Rat pelvic magnetic
      resonance images were acquired sequentially more than 2h after euthanasia by
      halothane overdose. A series of temperature difference maps in cooling dead rats
      was obtained with calculating imaging phase changes induced by the water proton
      frequency shift caused by temperature changes. Different cooling processes were
      monitored by the temperature difference maps in the rats. Magnetic resonance
      imaging thermometry applied in the study of laboratory animals could
      theoretically reproduce a variety of causes of death with different environmental
      conditions. Outcomes from experimental animal studies could be translated into a
      temperature-based time of death estimation in forensics.

PMID- 21940188
TI  - Postmortem changes of the thyroid on computed tomography.
AB  - OBJECTIVE: To evaluate the radiographic features of the thyroid on postmortem
      computed tomography (PMCT). METHODS: We studied the bodies of 32 subjects who had
      been treated and subsequently died in our tertiary care hospital between April
      and December 2009. The thyroids were imaged by antemortem computed tomography
      (AMCT), PMCT, and examined by conventional autopsy. Differences between the
      radiographic features of the thyroid on AMCT and PMCT, and time since AMCT were
      evaluated statistically. RESULTS: CT values of the thyroid decreased after death
      with an average of 114.2 Hounsfield Units (HUs) on AMCT vs. 107.7HU on PMCT
      (paired t-test, P=0.023). There was no correlation between the elapsed time from
      AMCT and differences of CT values of the thyroid on AMCT and PMCT (Spearman's
      rank correlation test, P>0.05). CONCLUSION: We showed that CT values of the
      thyroid decreased after death.

PMID- 21940189
TI  - Unexpected infant death due to hypoplastic left heart syndrome: a case report.
AB  - A female infant was found unresponsive at home. The mother alleged that she
      delivered the baby at home 13 days prior to the death. The mother did not have
      any prenatal examinations during the pregnancy and the infant was not examined by
      a doctor until death. The autopsy revealed that the cause of death was
      hypoplastic left heart syndrome (HLHS) and the infant's chest showed bilateral
      breast enlargement. Forensic pathologists may encounter very rare pathological
      findings with unexpected infant deaths. Some, like HLHS, are serious congenital
      heart defects related to the cause of death, and others are unique phenomena
      unrelated to the cause of death such as breast swelling and discharge called
      "witch's milk." In this case, we observed both findings.

PMID- 21940190
TI  - Expression of statherin mRNA and protein in nasal and vaginal secretions.
AB  - Nasal secretion has been regarded as one of the most difficult body fluids to
      identify and is especially difficult to discriminate from vaginal secretions and
      saliva. At present, few specific markers are known for nasal secretions. The aim
      of this study is to find a new approach for the identification of nasal
      secretions. We examined expression levels of statherin and histatin, peptides
      which are commonly found in saliva, in nasal and vaginal secretions by real-time
      RT-PCR and ELISA assays. Statherin mRNA was highly expressed in all nasal samples
      (dCt value=-1.49+/-1.10, n=8) and was detected even in 1-day-old 0.1-MUL stains.
      However, the stability of mRNA in nasal stains was significantly (P<0.01) lower
      than in saliva. Low levels of statherin mRNA were detected in 4 of the 17 vaginal
      samples (dCt value=11.65-14.72). Histatin mRNA was not detected in any nasal or
      vaginal samples, although it was highly expressed in all saliva samples. ELISA
      assays with anti-statherin goat polyclonal antibody showed that statherin peptide
      was detected in all nasal and saliva samples even after dilution of more than
      1000-fold. The statherin peptide was not detected in any vaginal samples,
      including samples that expressed low levels of statherin mRNA. The amount of
      statherin peptide in vaginal samples might be less than the limit of detection of
      this assay. In the present study, statherin was highly expressed in nasal
      secretions, but histatin was not. These markers may be useful for discriminating
      nasal secretions from vaginal secretions and saliva. However, the usefulness of
      these markers in practical forensic case samples has not yet been examined.
      Therefore, further research is required to establish the utility of these assays
      for identification of nasal secretions.

PMID- 21940191
TI  - Sonochemical synthesis of CuO nanostructures with different morphology.
AB  - This paper describes a highly efficient and rapid approach of synthesizing
      different CuO nanostructures in aqueous solutions using ultrasound irradiation of
      copper(II) acetate with urea/sodium hydroxide in the presence of
      polyvinylpyrrolidone (PVP), as stabilizing polymer. Field emission scanning
      electron microscope images clearly indicate the formation of CuO quasi-spherical
      microarchitectures and long-straw like structure in the presence of urea and
      sodium hydroxide. Other characterization techniques such as TEM, XRD and XPS are
      also provided to support the formation of such structures. One of the reasons for
      the formation of such CuO nanostructures may be due to the formation of a polymer
      metal complex with the stabilizing polymer (PVP).

PMID- 21940192
TI  - Ultrasound-assisted synthesis of aliphatic acid esters at room temperature.
AB  - This work describes the ultrasound-assisted synthesis of saturated aliphatic
      esters from synthetic aliphatic acids and either methanol or ethanol. The
      products were isolated in good yields after short reaction times under mild
      conditions.

PMID- 21940193
TI  - Identification of myocardial infarction (MI) using spatio-temporal heart
      dynamics.
AB  - Cardiovascular disorders, such as myocardial infarction (MI) are the leading
      causes of mortality in the world. This paper presents an approach that uses novel
      spatio-temporal patterns of the vectorcardiogram (VCG) signals for the
      identification of various types of MI. In contrast to the traditional
      electrocardiogram (ECG) approaches, the 3D cardiac VCG signal is partitioned into
      8 octants for localized analysis of the heart's electrical activities. The
      proposed method was tested using the PhysioNet PTB database for 368 MIs and 80
      healthy control (HC) recordings, each of which includes 12-lead ECG and 3-lead
      VCG. Significant differences are found in the VCG spatial distribution between MI
      and HC groups. Furthermore, classification and regression tree (CART) analysis
      was used to demonstrate that VCG octant features can distinguish MIs from HCs
      with a sensitivity (accuracy of MI identification) of 97.28% and a specificity
      (accuracy of HC identification) of 95.00%, which is promising compared to the
      previously reported results using other ECG databases. The results indicate that
      the present approach provides an effective way for monitoring, post-processing,
      and interpretation of ECG data, and hopefully can impact the current cardiac
      diagnostic practice.

PMID- 21940194
TI  - Mapping bipolar worlds: lived geographies of 'madness' in autobiographical
      accounts.
AB  - This article aims to advance our understanding of women's and men's experiences
      of negotiating bipolar 'madness' in society and space. It addresses gaps in the
      clinical literature on life with bipolar and geographic accounts of 'madness' and
      psycho-emotional distress by considering altered ways of being in place that
      bipolar 'madness' entails and how narrative sense is made of these. Conceptually,
      I build on Cosgrove's (2000) approach to psycho-emotional distress and geographic
      insights about being 'mad' in place. Methodologically and empirically, I draw on
      thematic narrative analysis of autobiographies of living with bipolar. Key
      findings include altered paradoxically (dis)embodied ways of being-in-place,
      'fractured' or 'whole' senses of self and ways of relating to people/places,
      'straddling' 'real' and 'delusional' worlds and bipolar ways of negotiating
      places are not straightforwardly 'irrational'. While narrative accounts most
      often invoke dominant discourses about bipolar, sometimes these are challenged
      through 'rescripting' and 'revaluing mad' identities and ways of being in place.
      In conclusion, key findings and avenues for future geographical research are
      discussed.

PMID- 21940195
TI  - Place-focused physical activity research, human agency, and social justice in
      public health: taking agency seriously in studies of the built environment.
AB  - Built environment characteristics have been linked to health outcomes and health
      disparities. However, the effects of an environment on behavior may depend on
      human perception, interpretation, motivation, and other forms of human agency. We
      draw on epidemiological and ethical concepts to articulate a critique of research
      on the built environment and physical activity. We identify problematic
      assumptions and enumerate both scientific and ethical reasons to incorporate
      subjective perspectives and public engagement strategies into built environment
      research and interventions. We maintain that taking agency seriously is essential
      to the pursuit of health equity and the broader demands of social justice in
      public health, an important consideration as studies of the built environment and
      physical activity increasingly focus on socially disadvantaged communities.
      Attention to how people understand their environment and navigate competing
      demands can improve the scientific value of ongoing efforts to promote active
      living and health, while also better fulfilling our ethical obligations to the
      individuals and communities whose health we strive to protect.

PMID- 21940197
TI  - Complex cannibalism: an unusual finding in oral squamous cell carcinoma.

PMID- 21940196
TI  - Slipping and sliding: frameshift mutations in herpes simplex virus thymidine
      kinase and drug-resistance.
AB  - Some of the most successful antiviral agents currently available are effective
      against herpes simplex virus. However, resistance to these drugs is frequently
      associated with significant morbidity, particularly in immunocompromised
      patients. In addition to the clinical implications of drug resistance, the range
      of biological processes exploited by the virus to attain resistance while
      maintaining pathogenicity is proving to be surprising. These mechanisms, which
      include ribosomal frameshifting, induced infidelity of the DNA polymerase, and
      internal ribosome entry, are discussed.

PMID- 21940198
TI  - Association of laser phototherapy with PRP improves healing of bisphosphonate
      related osteonecrosis of the jaws in cancer patients: a preliminary study.
AB  - The aim of this study was to compare retrospectively the effect of three
      different treatments on the healing outcome of bisphosphonate-related
      osteonecrosis of the jaws (BRONJ) in cancer patients. Twenty-two cancer patients
      were treated for BRONJ with one of the following protocols: clinical
      (pharmacological therapy), surgical (pharmacological plus surgical therapy), or
      PRP plus LPT (pharmacological plus surgical plus platelet rich plasma (PRP) plus
      laser phototherapy (LPT). The laser treatment was applied with a continuous diode
      laser (InGaAlP, 660 nm) using punctual and contact mode, 40 mW, spot size 0.042
      cm(2), 6 J/cm(2) (6 s) and total energy of 0.24 J per point. The irradiations
      were performed on the exposed bone and surrounding soft tissue. The analysis of
      demographic data and risk factors was performed by gathering the following
      information: age, gender, primary tumor, bisphosphonate (BP) used, duration of BP
      intake, history of chemotherapy, use of steroids, and medical history of
      diabetes. The association between the current state of BRONJ (with or without
      bone exposure) and other qualitative variables was determined using the chi
      square or Fisher's exact test. In all tests, the significance level adopted was
      5%. Most BRONJ lesions occurred in the mandible (77%) after tooth extraction
      (55%) and in women (72%). A significantly higher percentage of patients reached
      the current state of BRONJ without bone exposure (86%) in the PPR plus LPT group
      than in the pharmacological (0%) and surgical (40%) groups after 1-month follow
      up assessment. These results suggest that the association of pharmacological
      therapy and surgical therapy with PRP plus LPT significantly improves BRONJ
      healing in oncologic patients. Although prospective studies with larger sample
      sizes are still needed, this preliminary study may be used to inform a better
      designed future study.

PMID- 21940199
TI  - Raman spectroscopy of the multi anion mineral arsentsumebite Pb2Cu(AsO4)(SO4)(OH)
      and in comparison with tsumebite Pb2Cu(PO4)(SO4)(OH).
AB  - The mineral arsentsumebite Pb(2)Cu(AsO(4))(SO(4))(OH), a copper arsenate-sulphate
      hydroxide of the brackebuschite group has been characterised by Raman
      spectroscopy. The brackebuschite mineral group are a series of monoclinic
      arsenates, phosphates and vanadates of the general formula
      A(2)B(XO(4))(OH,H(2)O), where A may be Ba, Ca, Pb, Sr, while B may be Al,
      Cu(2+),Fe(2+), Fe(3+), Mn(2+), Mn(3+), Zn and XO(4) may be AsO(4), PO(4),
      SO(4),VO(4). Bands are assigned to the stretching and bending modes of SO(4)(2-)
      AsO(4)(3-) and HOAsO(3) units. Raman spectroscopy readily distinguishes between
      the two minerals arsentsumebite and tsumebite. Raman bands attributed to arsenate
      are not observed in the Raman spectrum of tsumebite. Phosphate bands found in the
      Raman spectrum of tsumebite are not found in the Raman spectrum of
      arsentsumebite. Raman spectroscopy readily distinguishes the two minerals
      tsumebite and arsentsumebite.

PMID- 21940200
TI  - Automatic detection of fast oscillations (40-200 Hz) in scalp EEG recordings.
AB  - OBJECTIVE: We aim to automatically detect fast oscillations (40-200 Hz) related
      to epilepsy on scalp EEG recordings. METHODS: The detector first finds localized
      increments of the signal power in narrow frequency bands. A simple classification
      based on two features, a narrowband to wideband signal amplitude ratio and an
      absolute narrowband signal amplitude, then allows for an important reduction in
      the number of false positives. RESULTS: When compared to an expert, the
      performance in 15 focal epilepsy patients resulted in 3.6 false positives per
      minute at 95% sensitivity, with at least 40% of the detected events being true
      positives. In most of the patients the channels showing the highest number of
      events according to the expert and the automatic detector were the same.
      CONCLUSIONS: A high sensitivity is achieved with the proposed automatic detector,
      but results should be reviewed by an expert to remove false positives.
      SIGNIFICANCE: The time required to mark fast oscillations on scalp EEG recordings
      is drastically reduced with the use of the proposed detector. Thus, the automatic
      detector is a useful tool in studies aiming to create a better understanding of
      the fast oscillations visible on the scalp.

PMID- 21940201
TI  - Mindfulness-induced changes in gamma band activity - implications for the default
      mode network, self-reference and attention.
AB  - OBJECTIVE: There is a growing scientific interest in mindfulness meditation (MM),
      yet its underlying neurophysiological mechanism is still uncertain. We
      investigated whether MM affects self-referential processing, associated with
      default mode network (DMN), either as short (state) - or long-term (trait)
      effects. METHODS: Three levels of MM expertise were compared with controls (n=12
      each) by electroencephalography (EEG). RESULTS: DMN deactivation was identified
      during the transition from resting state to a time production task, as lower
      gamma (25-45 Hz) power over frontal and midline regions. MM practitioners
      exhibited a trait lower frontal gamma activity, related to narrative self
      reference and DMN activity, as well as producing longer durations, these being
      negatively correlated with frontal gamma activity. Additionally, we found state
      increases in posterior gamma power, suggesting increased attention and sensory
      awareness. MM proficiency did not affect the results. CONCLUSIONS: Gamma power
      over frontal midline areas reflects DMN activity. MM practitioners exhibit lower
      trait frontal gamma activity, as well as a state and trait increases in posterior
      gamma power, irrespective of practice proficiency. SIGNIFICANCE: First, the DMN
      can be studied non-invasively by EEG. Second, MM induces from the early stages of
      practice neuroplasticity in self-referential and attentional networks.

PMID- 21940202
TI  - EEG in the 21st century: moving into the fast lane?

PMID- 21940203
TI  - Large-scale production of saikosaponins through root culturing of Bupleurum
      falcatum L. using modified airlift reactors.
AB  - Modification of internal configuration of a bubble column, airlift and stirred
      tank reactor (10-200 L) was made for root cultures of Bupleurum falcatum L.
      Agitation with an impeller covered with partition mesh was ineffective for a 10-L
      modified reactor, because it caused intensive foaming and subsequent overflow of
      the culture medium even at a low rotation speed of 50 rpm and a low aeration rate
      of 0.1 vvm (volume per volume of medium). In contrast, efficient aeration through
      a ceramic sparger placed at the bottom of a 20-L bubble column reactor yielded
      approximately 25 g/L of dry roots and 500 mg/L of saikosaponin-a and saikosaponin
      d over 42 days. On a 200-L scale, however, the roots became flocculated under the
      upper perforated plate initially positioned near the middle of the reactor,
      forming a firm disk of roots and a large empty space between the disk and the
      medium. Thus, the roots had poor contact with the medium, which severely
      suppressed their growth. To avoid this flocculation, a bottom perforated plate
      and draft tube were installed as a partitioning device separating the culturing
      area (outside the draft tube) from the aeration area (inside the draft tube). The
      draft tube was made of a stainless steel mesh rather than a solid material, and
      the tube greatly increased the root yield in the 20-L reactor. This configuration
      was successfully applied at the 200-L scale, yielding 500-600 mg/L of
      saikosaponin-a and saikosaponin-d over 56 days.

PMID- 21940204
TI  - Short sleep duration is associated with insulin resistance independent of
      adiposity in Chinese adult twins.
AB  - OBJECTIVE: To investigate the association between sleep duration and insulin
      resistance in rural Chinese adults and examine whether any such associations are
      independent of adiposity. METHODS: This is a cross-sectional analysis of 854 men
      and 640 women aged 20 to 70 years from the Anqing Twin Cohort. The following
      measures were obtained for each subject: Body mass index (BMI) and percentage of
      trunk fat (%TF), fasting plasma glucose, homeostatic model assessment of insulin
      resistance index (HOMA-IR), self-reported sleep duration and measures of snoring
      and sleep disturbance from the Pittsburgh Sleep Quality Indices (PSQI)
      questionnaire were modified for a Chinese population. Multivariate linear
      regressions were applied to examine the association of sleep duration with HOMA
      IR, with and without adjustment for adiposity variables, along with other
      relevant covariates. RESULTS: In this sample of relatively lean rural Chinese
      adults, short sleep duration was associated with HOMA-IR in women but not in men.
      In women, short (<= 7 h/night) sleep duration was associated with a higher HOMA
      IR (p=0.003) compared with normal sleep duration (>7 to <= 8 h/night) after
      adjustment for all the covariates except adiposity. Further adjustment for BMI or
      %TF attenuated the sleep-HOMA-IR association, but the association remained
      significant upon adjustment for BMI (p=0.013); and upon adjustment for %TF
      (p=0.026). Long sleep duration (> 8 h/night) was not significantly associated
      with HOMA-IR. CONCLUSION: In this rural Chinese cohort, short sleep duration is
      independently associated with increased insulin resistance among women only, even
      after adjusting for adiposity and other potential confounders.

PMID- 21940206
TI  - Parental functioning and pediatric sleep disturbance: an examination of factors
      associated with parenting stress in children clinically referred for evaluation
      of insomnia.
AB  - BACKGROUND: Parenting stress is an aspect of parent functioning relevant in
      clinical settings. Within the context of behavioral sleep medicine, the role of
      parenting stress is not well understood. METHODS: Prospective evaluation of
      patients 1.5-10 years old with insomnia. Subjects were 156 primary caregiver
      child pairs who completed the Parenting Stress Index-Short Form (PSI-SF), Child
      Sleep Habits Questionnaire (CSHQ) and Child Behavior Checklist (CBCL). AIMS: (1)
      determine prevalence of clinically significant parenting stress in primary
      caregivers of children clinically referred for insomnia; (2) identify childhood
      sleep problems that play a role in parenting stress; (3) identify relevant
      correlates of parenting stress within the context of a behavioral sleep medicine
      clinic; and (4) identify the most salient child sleep and behavioral variables
      associated with parenting stress. RESULTS: Forty-seven percent of primary
      caregivers had clinically significant parenting stress. When examining the
      relationship between child sleep problems and parenting stress, bedtime
      resistance (p=0.030) and daytime sleepiness (p=0.0003) stood alone as having the
      most salient associations with parenting stress. When considering a broader range
      of covariates (child age and child gender) and clinically relevant variables
      (parent history of sleep problems, parent history of psychiatric conditions,
      child behavior problems and child sleep problems) in a single regression
      equation, both child externalizing behavior problems (beta=0.570, p<0.0001) and
      child daytime sleepiness (beta=0.152, p=0.028) independently explained
      significant variability in parenting stress. CONCLUSIONS: Many primary caregivers
      of children clinically-referred for insomnia evaluation and treatment have
      significant parenting stress. Parenting stress is associated with daytime
      behavioral problems and sleepiness in children with insomnia. Clinicians working
      with pediatric insomnia patients should carefully evaluate parenting stress and
      child daytime behavior as these aspects of functioning may have an impact on
      service delivery and treatment outcomes.

PMID- 21940207
TI  - Allocation of reliable analytical procedures for human biomonitoring published by
      the DFG Senate Commission for the Investigation of Health Hazards of Chemical
      Compounds in the Work Area.
AB  - In 1955 the Senate Commission for the Investigation of Health Hazards of Chemical
      Compounds in the Work Area (MAK Commission) was founded by the Deutsche
      Forschungsgemeinschaft (DFG). The Commission is responsible for analysing health
      risks by chemical exposure at the workplace and for advising public authorities
      accordingly. Within the Commission, the working group "Analyses of Hazardous
      Substances in Biological Materials" (AiBM) deals with the development of
      procedures to analyse chemical substances in biological materials. Most of these
      detailed, ready-to-use protocols for human biomonitoring, do not only enable the
      monitoring of occupational exposure, but also the determination of the background
      exposure in the general population. The AiBM working group applies a multi-stage
      process to develop and evaluate human biomonitoring methods. As a matter of
      special importance, every method is tested by at least one examiner to ensure
      reproducibility of the analytical procedure and of the reliability data.
      Submitted methods and examination reports are discussed within the working group.
      The positively proved methods, if satisfactory, are adopted for publication.
      Otherwise, they are given back to the author with the demand for revision. In
      case of fundamental drawbacks, methods are rejected. The adopted methods are
      published in German and in English at regular intervals. Since 1985 the working
      group has published 129 analytical methods (plus 11 methods for markers of
      susceptibility) in 12 issues of the English edition. The detection limits of
      eighty methods allow the analyses of background exposure for one or more
      parameters. About forty methods were specially designed for the application in
      population studies. Particularly relevant method examples are the determination
      of the metabolites of organophosphate pesticides, pyrethroides and phthalates in
      urine as well as the determination of perfluorinated compounds and
      polychlorinated biphenyls in serum.

PMID- 21940205
TI  - Sleep in children with Williams Syndrome.
AB  - OBJECTIVE: To analyze sleep in children with Williams Syndrome (WS) compared to
      normal healthy controls in order to determine whether particular sleep features
      are characteristic of WS, and to explore associations between disturbed sleep and
      behavior. METHODS: Thirty-five children with genetically-confirmed WS and 35
      matched controls underwent overnight polysomnography and performance testing in
      the Sleep Center at the Children's Hospital of Philadelphia. Parents completed
      questionnaires regarding the subjects' sleep and behavior. RESULTS: WS subjects
      had significantly different sleep than controls, with decreased sleep efficiency,
      increased respiratory-related arousals and increased slow wave sleep on overnight
      polysomnography. WS subjects were also noted to have more difficulty falling
      asleep, with greater restlessness and more arousals from sleep than controls.
      Fifty-two percent of WS subjects had features of attention deficit-hyperactivity
      disorder. CONCLUSION: Children with WS had significantly different sleep than
      controls in our sample. These differences demonstrated in our study may reflect
      genetic influences on sleep.

PMID- 21940208
TI  - The First Nations Biomonitoring Initiative-FNBI.
AB  - The First Nations Biomonitoring Initiative (FNBI) pilot study was implemented in
      the winter 2010/2011, sampling 252 First Nations people on reserve in Canada for
      a suite of chemical contaminants following Cycle 1 of the Canadian Health
      Measures Survey (CHMS). Results will be sent confidentially to participants and a
      community report will be presented after the analysis of results, expected to be
      completed by fall of 2011. The national scale of the study will take place during
      the summer 2011/2012 and aims to sample thirteen communities with a participation
      of 42 First Nations people per community. Results are expected for spring
      2012/2013.

PMID- 21940209
TI  - Harmonised human biomonitoring in Europe: activities towards an EU HBM framework.
AB  - Human biomonitoring (HBM) can be an effective tool to assess human exposure to
      environmental pollutants and potential health effects and is increasingly seen as
      an essential element in a strategy when integrating health and environment. HBM
      can be used (i) to prioritise actions and measures for policy making; (ii) to
      evaluate policy actions aimed at reducing exposure to potentially hazardous
      environmental stressors; and (iii) to promote more comprehensive health impact
      assessments of policy options. In support of the European Environment and Health
      Action Plan 2004-2010, European scientists, experts from authorities and other
      stakeholders joined forces to work towards developing a functional framework and
      standards for a coherent HBM in Europe. Within the European coordination action
      on human biomonitoring, 35 partners from 27 European countries in the COPHES
      consortium aggregated their experiences and expertise and developed harmonized
      approaches and recommendations for better comparability of HBM data in Europe via
      the elaboration of a harmonized study protocol. This protocol is the product of
      discussion and compromises on the selection of environmental exposures, national
      environmental health concerns, and political and health priorities. The
      harmonised approach includes sampling recruitment, and analytical procedures,
      communication strategies and biobanking initiatives. The protocols and the
      harmonised approach are a means to increase acceptance and policy support and to
      in the future to enable determination of time trends. The common pilot study
      protocol will shortly be tested, adapted and assessed in the framework of the
      DEMOCOPHES in 17 European countries, including 16 EU Member States. COPHES and
      DEMOCOPHES constitute important steps towards establishing human biomonitoring as
      a tool for EU environmental and health policy and to improve quantification of
      exposure of the general European population to existing and emerging pollutants.

PMID- 21940210
TI  - Highlights of recent studies and future plans for the French human biomonitoring
      (HBM) programme.
AB  - This manuscript presents highlights of recent studies and perspectives from the
      French human biomonitoring (HBM) programme. Until recently, HBM studies focused
      on specific populations or pollutants to gain a better understanding of exposure
      to environmental chemicals, to help regulators reduce environmental exposure and
      to monitor existing policies on specific concerns. Highlights of recent
      multicentre biomonitoring studies with specific population or pollutant focus are
      given. These French HBM studies have been implemented to know: (1) the influence
      of living near an incinerator on serum dioxin and polychlorinated biphenyl (PCB)
      levels, (2) the influence of consuming river fish contaminated by PCBs on serum
      PCBs of fishermen, and (3) the evolution of blood lead levels in children from 1
      to 6 years old since 1995. Special emphasis is placed on the use of an integrated
      (HBM coupled with nutrition and health studies), multipollutant approach. This
      approach has been initiated in France with a recent national population-based
      biomonitoring survey, the Etude Nationale Nutrition Sante (ENNS; French Nutrition
      and Health Survey). This survey will provide the first reference distribution for
      42 biomarkers in the French population. The current national HBM strategy will
      build upon the ENNS and include a national survey of people aged between 6 and 74
      years complemented for the neonatal period and childhood by the Etude
      Longitudinale Francaise depuis l'Enfance (ELFE; French longitudinal study of
      children). France also contributes to the harmonization of HBM activities in
      Europe through participation in European HBM projects.

PMID- 21940211
TI  - Voices in the playground: a qualitative exploration of the barriers and
      facilitators of lunchtime play.
AB  - OBJECTIVES: To explore children's perceptions of the factors influencing their
      engagement in physical activity during the "critical" lunchtime period, using a
      social-ecological framework. DESIGN: This study was an in-depth descriptive
      qualitative design. METHODS: Fifty-four South Australian children aged 10-13
      years participated in same-gender focus groups. Transcripts, field notes and
      activity documents were analysed using content analysis. Using an inductive
      thematic approach, data were coded and categorised into perceived barriers and
      facilitators according to a social-ecological model. RESULTS: Children identified
      a range of environmental, social and intrapersonal barriers and facilitators.
      Bullying/teasing, the school uniform and school rules were exposed as explicit
      barriers to lunchtime play. Other important barriers included lack of access to,
      and poor suitability of, space, lack of access to programs/facilities and
      equipment, and lack of peer and teacher support. Perceived facilitators of
      lunchtime physical activity centred on access to equipment, enjoyment, motivation
      to improve skills, and peer support and acceptance. The freedom to make up or
      modify rules for games was also perceived to be a facilitator of lunchtime play.
      CONCLUSIONS: Communicating with children has been an effective approach in
      uncovering perceived barriers and facilitators to lunchtime play that may not
      have been previously considered in the quantitative correlate literature.
      Lunchtime interventions targeting children's physical activity should focus on
      addressing the barriers perceived to be important to lunchtime play.

PMID- 21940212
TI  - Hot ambient conditions do not alter intermittent cycling sprint performance.
AB  - OBJECTIVES: To investigate the effect of hot exposure on the ability to perform
      intermittent cycling sprints. DESIGN: Repeated measures. METHODS: Ten male
      volunteers performed 35 min of intermittent cycling comprising of 8 maximal 6-s
      sprints interspersed by 1 min of passive recovery followed by 4 min of constant
      load pedaling (1 W kg(-1) of body weight) on a cycle ergometer in control (24
      degrees C, 24%rH) and hot (40 degrees C, 40%rH) environments. RESULTS: Peak power
      output did not decrease during the exercise and was not dependent on the
      environmental temperature (average of 767+/-120 W in control and 767+/-119 W in
      hot, NS). Skin temperatures (e.g., chest: 36.8+/-0.8 vs. 32.7+/-0.6 degrees C),
      heart rate (132+/-13 vs. 118+/-13 bpm) and rating of perceived exertion (13+/-3
      vs. 11+/-3) were higher (all p<.05) in hot than control environment. However, EMG
      activity (RMS, vastus lateralis) and neuromuscular efficiency (power/RMS ratio)
      were similar at the two environmental conditions. CONCLUSIONS: Despite higher
      cardiovascular and perceptual strain in the hot trial, heat exposure did not
      alter neither peak power output nor related muscle activation and neuromuscular
      efficiency in the absence of hyperthermia (average core temperature of 37.6+/-0.3
      degrees C in control vs. 37.7+/-0.4 degrees C in hot, NS).

PMID- 21940213
TI  - Acute neuromuscular and fatigue responses to the rest-pause method.
AB  - OBJECTIVES: To compare muscle recruitment, maximal force, and rate of force
      development changes following different resistance exercise protocols with a
      constant volume-load. DESIGN: Within-subjects randomized crossover trial.
      METHODS: Fourteen (n=14) resistance trained male participants completed three
      different resistance exercise protocols involving 20 squat repetitions,
      prescribed at 80% of 1-repetition-maximum. Protocol A consisted of 5 sets of 4
      repetitions with 3 min inter-set rest intervals, protocol B was 5 sets of 4
      repetitions with 20 s inter-set rest intervals, and the rest-pause method was an
      initial set to failure with subsequent sets performed with a 20 s inter-set rest
      interval. Maximal squat isometric force output and rate of force development
      (RFD) were measured before, immediately upon completion (IP), and 5 min (5P)
      following each protocol. Muscle activity from 6 different thigh and hip muscles
      was measured with surface electromyography (EMG) at each time point, and during
      every squat repetition. RESULTS: Participants completed the rest-pause method in
      2.1+/-0.4 sets, with a total protocol duration of 103 s compared to 140 s and 780
      s for protocols B and A, respectively. All protocols elicited similar decreases
      (p<0.05) in maximal force and RFD at IP, with full recovery at 5P. Increased
      motor unit recruitment was observed during the rest-pause method compared to both
      protocols A and B for all muscles measured (p<0.05). CONCLUSIONS: As a result of
      the increased EMG during exercise and no greater post-exercise fatigue, it was
      concluded that the rest-pause method may be an efficacious training method for
      resistance-trained individuals.

PMID- 21940215
TI  - Rituximab in DLBCL: 6 years on.

PMID- 21940216
TI  - Cytosolic DNA sensors regulating type I interferon induction.
AB  - Type I interferon (IFN) induction is a crucial anti-pathogen response mediated by
      innate immune stimulation. Although it has been appreciated for some time that
      the presence of pathogen DNA within a cell leads to a type I IFN response, it is
      only in the past few years that some of the key signalling proteins and DNA
      sensors that regulate this response have been uncovered. Here, we review the
      nature of these DNA sensors, which include a new family of pattern recognition
      receptors termed the AIM2-like receptors, and consider the implications of their
      discovery for understanding emerging principles of innate immune DNA sensing.
      Furthermore, we discuss how their discovery provides a rationale as to why
      accumulation of self-DNA mediates IFN-dependent autoimmunity.

PMID- 21940218
TI  - Reading performance in children with rolandic epilepsy correlates with nocturnal
      epileptiform activity, but not with epileptiform activity while awake.
AB  - OBJECTIVE: An association between language impairment and rolandic epilepsy is
      frequently reported. This impairment could be correlated with the amount of
      nocturnal epileptiform activity. METHODS: We retrospectively analyzed 26 children
      with rolandic epilepsy and/or rolandic spikes. All had undergone a 24-hour EEG
      and neuropsychological assessment within 2 weeks. Reading performance (reading
      words and sentences) and intelligence were measured. RESULTS: There was a
      significant negative correlation between amount of nocturnal epileptiform
      activity and reading sentences R=-0.525 (P=0.008). There was a trend in this
      correlation for reading words R=-0.398 (P=0.054). We found a negative correlation
      between amount of nocturnal epileptiform activity and Verbal IQ (R=-0.51 P=0.08).
      No correlation was found between reading performance or Verbal IQ and amount of
      diurnal epileptiform activity. CONCLUSIONS: Reading performance is impaired in
      children with rolandic epilepsy and is correlated with the amount of nocturnal
      epileptiform activity.

PMID- 21940214
TI  - CHOP-like chemotherapy with or without rituximab in young patients with good
      prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label
      randomised study of the MabThera International Trial (MInT) Group.
AB  - BACKGROUND: The MInT study was the first to show improved 3-year outcomes with
      the addition of rituximab to a CHOP (cyclophosphamide, doxorubicin, vincristine,
      and prednisone)-like regimen in young patients with good-prognosis diffuse large
      B-cell lymphoma. Extended follow-up was needed to establish long-term effects.
      METHODS: In the randomised open-label MInT study, patients from 18 countries
      (aged 18-60 years with none or one risk factor according to the age-adjusted
      International Prognostic Index [IPI], stage II-IV disease or stage I disease with
      bulk) were randomly assigned to receive six cycles of a CHOP-like chemotherapy
      with or without rituximab. Bulky and extranodal sites received additional
      radiotherapy. Randomisation was done centrally with a computer-based tool and was
      stratified by centre, bulky disease, age-adjusted IPI, and chemotherapy regimen
      by use of a modified minimisation algorithm that incorporated a stochastic
      component. Patients and investigators were not masked to treatment allocation.
      The primary endpoint was event-free survival. Analyses were by intention to
      treat. This observational study is a follow-up of the MInT trial, which was
      stopped in 2003, and is registered at ClinicalTrials.gov, number NCT00400907.
      FINDINGS: The intention-to-treat population included 410 patients assigned to
      chemotherapy alone and 413 assigned to chemotherapy plus rituximab. After a
      median follow-up of 72 months (range 0.03-119), 6-year event-free survival was
      55.8% (95% CI 50.4-60.9; 166 events) for patients assigned to chemotherapy alone
      and 74.3% (69.3-78.6; 98 events) for those assigned to chemotherapy plus
      rituximab (difference between groups 18.5%, 11.5-25.4, log-rank p<0.0001).
      Multivariable analyses showed that event-free survival was affected by treatment
      group, presence of bulky disease, and age-adjusted IPI and that overall survival
      was affected by treatment group and presence of bulky disease only. After
      chemotherapy and rituximab, a favourable subgroup (IPI=0, no bulk) could be
      defined from a less favourable subgroup (IPI=1 or bulk, or both; event-free
      survival 84.3% [95% CI 74.2-90.7] vs 71.0% [65.1-76.1], log-rank p=0.005). 18
      (4.4%, 95% CI 2.6-6.9) second malignancies occurred in the chemotherapy-alone
      group and 16 (3.9%, 2.2-6.2) in the chemotherapy and rituximab group (Fisher's
      exact p=0.730). INTERPRETATION: Rituximab added to six cycles of CHOP-like
      chemotherapy improved long-term outcomes for young patients with good-prognosis
      diffuse large-B-cell lymphoma. The definition of two prognostic subgroups allows
      a more refined therapeutic approach to these patients than does assessment by IPI
      alone. FUNDING: Hoffmann-La Roche.

PMID- 21940217
TI  - Targeting B cell responses in universal influenza vaccine design.
AB  - Since its first administration in the 1940s, the influenza vaccine has provided
      tremendous relief against influenza infections. However, time has revealed the
      ultimate limit of the vaccine and the call for its reinvention has now come, just
      as we are beginning to appreciate the antibody immune responses vital in
      preventing infections. New strategies to design the influenza vaccine rely on
      selectively inducing broadly neutralizing antibodies that are specific for highly
      conserved viral epitopes. Such approaches take us away from the limited range of
      protection provided by current seasonal influenza vaccines and towards a future
      with a pan-influenza vaccine capable of providing universal strain coverage.

PMID- 21940219
TI  - Splenic rupture as complication of sleeve gastrectomy.

PMID- 21940220
TI  - Does intraabdominal pressure affect development of subcutaneous emphysema at
      gynecologic laparoscopy?
AB  - STUDY OBJECTIVE: To estimate the effect of intraabdominal pressure and risk
      factors related to the occurrence of subcutaneous emphysema during laparoscopic
      surgery. DESIGN: Prospective randomized study (Canadian Task Force classification
      I). SETTING: University hospital. PATIENTS: Two hundred patients who underwent
      gynecologic laparoscopy because of benign gynecologic disease or cervical
      intraepithelial neoplasia. INTERVENTIONS: Gynecologic laparoscopy. MEASUREMENTS
      AND MAIN RESULTS: Before surgery, patients were divided randomly into 2 groups.
      During surgery, the first group were limited to 12 mm Hg intraabdominal pressure
      (n = 100), and the second group 10 mm Hg intraabdominal pressure (n = 100). The
      incidence of subcutaneous emphysema in each group and the relationship between
      subcutaneous emphysema and operation time, table tilt angle, patient age, body
      mass index (BMI) and end-tidal CO(2) (ETco(2)) were analyzed. The occurrence of
      subcutaneous emphysema was significantly lower in the group 2 than in group 1 (p
      = .02). The BMI was significantly lower (p = .02), and peak ETco(2) significantly
      higher (p < .001) in the group in which subcutaneous emphysema developed.
      However, there were no significant differences in age, operative time, table tilt
      angle, number of ports used, and initial ETco(2) between the groups with and
      without subcutaneous emphysema. CONCLUSIONS: The incidence of subcutaneous
      emphysema increased with higher intraabdominal pressure during gynecology
      laparoscopy. Low BMI and increased intraoperative ETco(2) concentration were also
      related to the occurrence of subcutaneous emphysema.

PMID- 21940221
TI  - The role of Bacillus anthracis RecD2 helicase in DNA mismatch repair.
AB  - DNA mismatch repair (MMR) systems can be classified as either MutH-dependent or
      MutH-independent. In bacteria, extensive studies have been conducted with the
      MutH-dependent MMR in Escherichia coli and its close relatives. The picture of
      MutH-independent MMR in other bacteria is less clear, as MMR components other
      than MutS and MutL have not been identified in the majority of bacteria. Bacillus
      anthracis is one of the MutH-less Gram(+) bacteria in the phylum of Firmicutes.
      We used papillation as a tool to search for B. anthracis new mutator strains and
      identified a spontaneous mutator that carries a minitransposon insertion in the
      BAS4289 locus. The mutational frequency and specificity exhibited in this mutant
      were comparable to that of MMR-deficient strains with knockouts of mutL or mutS.
      It retained a similar UV sensitivity profile as that of the wild type. BAS4289
      encodes a putative DNA helicase RecD2 that shares 30% sequence identity with
      Deinococcus radiodurans RecD2, a well characterized superfamily 1B helicase whose
      homologs are widely present in Firmicutes complete genomes. We demonstrated that
      the N-terminal region of RecD2, a unique sequence extension used to distinguish
      RecD2 from RecD1, was important for B. anthracis RecD2, as mutations in the N
      terminal conserved motifs affected its DNA repair function. This is the first
      report of a RecD2 helicase being associated with MMR. RecD2 and our recently
      described YycJ protein are likely to be two additional components in the B.
      anthracis MutH-independent MMR system.

PMID- 21940222
TI  - Conformational changes and bioactivity of lysozyme on binding to and desorption
      from magnetite nanoparticles.
AB  - A fundamental understanding of the conformational behaviors of lysozyme during
      the process of adsorption and desorption has been studied using
      spectrophotometric techniques, and interpreted in terms of the secondary
      structures in this work. FTIR data show an increase in alpha-helix and beta-sheet
      content when lysozyme interaction with magnetite nanoparticles (Fe(3)O(4) (PEG+CM
      CTS) NPs) which indicates that the lysozyme would adopt a more compact
      conformation state. The mechanism of fluorescence quenching of lysozyme by
      magnetite nanoparticles is due to the formation of lysozyme-nanoparticles
      complex. High desorption of lysozyme from Fe(3)O(4) (PEG+CM-CTS) NPs were
      achieved using phosphate buffer solution (PBS) (20 mM, pH 5.0, 0.2 M NaCl), PBS
      (20 mM, pH 5.0, 0.5 M NaCl) and acetic acid (0.2 M, pH 4.0) as eluents. The
      alterations of lysozyme secondary structure on desorption from nanoparticles were
      confirmed by circular dichroism and fluorescence spectroscopy. Lysozymes desorbed
      by PBS (20mM, pH 5.0, 0.2M NaCl) and PBS (20mM, pH 5.0, 0.5M NaCl) retain high
      fraction of its native structure with negligible effect on its activity, and
      about 92.4% and 89.5% activity were retained upon desorption from nanoparticles,
      however, lysozyme desorbed by acetic acid (0.2 M, pH 4.0) solution showed
      significant conformational changes. The stability of NPs-conjugated protein and
      retention of higher activity may find useful applications in biotechnology
      ranging from enzyme immobilization to protein purification.

PMID- 21940223
TI  - Measuring weight outcomes for obesity intervention strategies: the case of a
      sugar-sweetened beverage tax.
AB  - Taxing unhealthy foods has been proposed as a means to improve diet and health by
      reducing calorie intake and raising funds to combat obesity, particularly sugar
      sweetened beverages (SSBs). A growing number of studies have examined the effects
      of such food taxes, but few have estimated the weight-loss effects. Typically, a
      static model of 3500 calories for one pound of body weight is used, and the main
      objective of the study is to demonstrate its bias. To accomplish the objective,
      we estimate income-segmented beverage demand systems to examine the potential
      effects of a SSB tax. Elasticity estimates and a hypothetical 20 percent
      effective tax rate (or about 0.5 cent per ounce) are applied to beverage intake
      data from a nationally representative survey, and we find an average daily
      reduction of 34-47 calories among adults and 40-51 calories among children. The
      tax-induced energy reductions are translated into weight loss using both static
      and dynamic calorie-to-weight models. Results demonstrate that the static model
      significantly overestimates the weight loss from reduced energy intake by 63
      percent in year one, 346 percent in year five, and 764 percent in year 10, which
      leads to unrealistic expectations for obesity intervention strategies. The tax is
      estimated to generate $5.8 billion a year in revenue and is found to be
      regressive, although it represents about 1 percent of household food and beverage
      spending.

PMID- 21940224
TI  - [Centile values for serum lipids in Colombian adolescents].
AB  - OBJECTIVE: To assess age- and sex-specific percentile baseline data for total
      cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol
      (HDL-C) in Colombian children and adolescents aged 10 to 17 years. PATIENTS AND
      METHODS: A cross-sectional, descriptive study was conducted on 1,773 children and
      adolescents. Each participant underwent a fasting measurement to quantify TC, HDL
      C, and TG levels using enzymatic-colorimetric methods. Smoothed age- and sex
      specific 5(th), 25(th), 50(th), 75(th), 90(th) and 95(th) percentile values where
      derived using LMS regression (Least Mean Square) using the statistical package
      Growth Analyzer. RESULTS: Overall, males had lower serum TC and TG levels as
      compared to females. P95 of TG and TC was higher in males aged 10 to 14 years as
      compared to females, while HDL-C levels were similar in both sexes. CONCLUSIONS:
      Percentile values will help classify children and adolescents as compared to
      other populations based on this health indicator.

PMID- 21940228
TI  - [Study of iodine intake in children from 6 months to three years-old in
      Guipuzcoa].
AB  - OBJECTIVE: To assess whether iodine deficiency exists in healthy children aged 6
      months to 3 years by measuring urinary iodine. DESIGN: A descriptive, cross
      sectional study using purposeful sampling of children who attended 10 Primary
      Health Care centres in Guipuzcoa for routine health examinations. SUBJECTS: A
      total of 130 healthy children aged between 6 and 36 months, of whom 61 (46.9%)
      were girls and 69 (53.1%) boys. MEASUREMENTS: Age in months, origin, sex,
      nutritional survey (particularly intake of iodised salt, sea fish and dairy
      products) and urinary iodine excretion in a random urine sample. RESULTS: The
      median urinary iodine was 127 MUg/L. About one third (36.9%) of children had a
      urinary iodine below 100 MUg/L. No relationship was found between urinary iodine
      and nutritional survey variables. CONCLUSION: Iodine intake in the children
      studied is adequate according to WHO recommendations.

PMID- 21940229
TI  - When should pelvic sentinel lymph nodes be harvested in patients with malignant
      melanoma?
AB  - BACKGROUND: Preoperative lymphoscintigraphy for sentinel node biopsy (SNB)
      combined with intra-operative gamma-probe detection often identifies nodes within
      the pelvis. This study investigates the role of pelvic SNB harvest. METHODS:
      Retrospective review of eighty-two stage I/II melanoma patients with primary
      tumour on the lower limb and trunk who underwent groin SNB, either inguinal or
      pelvic or both, over a three year period. RESULTS: Of the 82 patients, 19 had
      positive SNBs (24%), all of which were inguinal nodes. None of the 11 patients
      with pelvic nodes removed had a positive pelvic node. The median follow-up period
      was 18 months (SD: 10.8; range: 8-43). Although the complication rate was higher
      following pelvic SNB, the difference was not statistically significant (p > 0.5).
      The average operative time for an inguinal SNB was 92 min, and increased
      significantly to 134 min for a pelvic SNB (p < 0.0001). Lymphoscintigraphy of
      trunk and thigh melanomas identified individual tracks to be leading directly
      from the tumour to a pelvic node(s). However, when the primary tumour was located
      at or below the knee, pelvic nodes identified by lymphoscintigraphy appeared to
      be second level nodes. CONCLUSION: A lymphoscintigraphy protocol that includes
      dynamic images obtained in frequent intervals following injection of the
      radiotracer combined with thorough preoperative analysis of the
      lymphoscintigraphy scans and effective communication between the radiologist and
      the surgeon allows accurate identification of the primary tracks and prevent
      unnecessary harvest of second echelon pelvic lymph nodes. In patients with
      significant co-morbidities due consideration is required before harvesting pelvic
      sentinel nodes.

PMID- 21940230
TI  - Plastic incunabula -- a tale of Carpue's Tagliacozzi's.
AB  - Carpue's An Account of Two Successful Operations caused the rebirth of plastic
      surgery in 1816 over 200 years after the first plastic surgery book was written
      by Tagliacozzi. Tagliacozzi's book was pirated with both authorized edition and
      unauthorized editions having been published in 1597. In his book, Carpue reviewed
      the literature including Tagliacozzi's work. Carpue had Charles Turner, engraver
      in-ordinary to the King prepare his books illustrations. Comparing Turner's
      engraving with those in the original and pirated editions of Tagliacozzi's book
      shows that Turner duplicated the pirated edition. The author discovered a pirated
      edition at St. Bartholomew's Medical College Library in 1971 that was signed by
      Carpue and shows how by comparing the illustrations in it with those in Carpue's
      book that this was the working copy used by Turner. In 1819 Carpue gave this book
      to a "B. Turner Jr." who probably was Turner's teenage son who later became a
      surgeon. In 2011 the author discovered an authorized version of Tagliacozzi's
      book signed by Carpue at the Lilly Library in Indiana. These books are important
      links in the history of plastic surgery.

PMID- 21940231
TI  - Managing women with acute physiological deterioration: student midwives
      performance in a simulated setting.
AB  - OBJECTIVE: Midwives' ability to manage maternal deterioration and 'failure to
      rescue' are of concern with questions over knowledge, clinical skills and the
      implications for maternal morbidity and, mortality rates. In a simulated setting
      our objective was to assess student midwives' ability to assess, and manage
      maternal deterioration using measures of knowledge, situation awareness and
      skill, performance. METHODS: An exploratory quantitative analysis of student
      performance based upon performance, ratings derived from knowledge tests and
      observational ratings. During 2010 thirty-five student, midwives attended a
      simulation laboratory completing a knowledge questionnaire and two video,
      recorded simulated scenarios. Patient actresses wearing a 'birthing suit'
      simulated deteriorating, women with post-partum and ante-partum haemorrhage (PPH
      and APH). Situation awareness was, measured at the end of each scenario.
      Applicable descriptive and inferential statistical tests were, applied to the
      data. FINDINGS: The mean total knowledge score was 75% (range 46-91%) with low
      skill performance, means for both scenarios 54% (range 39-70%). There was no
      difference in performance between the scenarios, however performance of key
      observations decreased as the women deteriorated; with significant reductions in
      key vital signs such as blood pressure and blood loss measurements. Situation,
      awareness scores were also low (54%) with awareness decreasing significantly
      (t(32)=2.247, p=0.032), in the second and more difficult APH scenario.
      CONCLUSION: Whilst knowledge levels were generally good, skills were generally
      poor and decreased as the women deteriorated. Such failures to apply knowledge in
      emergency stressful situations may be resolved by repetitive high stakes and high
      fidelity simulation.

PMID- 21940232
TI  - MtDNA SNP multiplexes for efficient inference of matrilineal genetic ancestry
      within Oceania.
AB  - Human mitochondrial DNA (mtDNA) is a convenient marker for tracing matrilineal
      bio-geographic ancestry and is widely applied in forensic, genealogical and
      anthropological studies. In forensic applications, DNA-based ancestry inference
      can be useful for finding unknown suspects by concentrating police investigations
      in cases where autosomal STR profiling was unable to provide a match, or can help
      provide clues in missing person identification. Although multiplexed mtDNA single
      nucleotide polymorphism (SNP) assays to infer matrilineal ancestry at a (near)
      continental level are already available, such tools are lacking for the Oceania
      region. Here, we have developed a hierarchical system of three SNaPshot
      multiplexes for genotyping 26 SNPs defining all major mtDNA haplogroups for
      Oceania (including Australia, Near Oceania and Remote Oceania). With this system,
      it was possible to conclusively assign 74% of Oceanian individuals to their
      Oceanian matrilineal ancestry in an established literature database (after
      correcting for obvious external admixture). Furthermore, in a set of 161
      genotyped individuals collected in Australia, Papua New Guinea and Fiji, 87.6%
      were conclusively assigned an Oceanian matrilineal origin. For the remaining
      12.4% of the genotyped samples either a Eurasian origin was detected indicating
      likely European admixture (1.9%), the identified haplogroups are shared between
      Oceania and S/SE-Asia (5%), or the SNPs applied did not allow a geographic
      inference to be assigned (5.6%). Sub-regional assignment within Oceania was
      possible for 32.9% of the individuals genotyped: 49.5% of Australians were
      assigned an Australian origin and 13.7% of the Papua New Guineans were assigned a
      Near Oceanian origin, although none of the Fijians could be assigned a specific
      Remote Oceanian origin. The low assignment rates of Near and Remote Oceania are
      explained by recent migrations from Asia via Near Oceania into Remote Oceania.
      Combining the mtDNA multiplexes for Oceania introduced here with those we
      developed earlier for all other continental regions, global matrilineal bio
      geographic ancestry assignment from DNA is now achievable in a highly efficient
      way that is also suitable for applications with limited material such as forensic
      case work.

PMID- 21940233
TI  - Impact of an educational intervention on caregivers' beliefs about infant crying
      and knowledge of shaken baby syndrome.
AB  - OBJECTIVE: Shaken baby syndrome (SBS) is the leading cause of traumatic infant
      death. We examined whether the message about not shaking an infant should be
      included in the newborn anticipatory guidance provided by pediatric residents.
      The aim of this study was to determine the impact of an educational intervention
      (Take 5 Safety Plan for Crying) delivered by pediatric residents at newborn
      hospital discharge on beliefs about infant crying and knowledge of SBS among
      caregivers of young infants being treated in an urban primary care center.
      METHODS: Structured interviews were done in one convenience sample of caregivers
      before (historical control group) and in a second set of different caregivers
      after (intervention group) an educational intervention was implemented at
      hospital discharge. Logistic regression was used to calculate adjusted
      associations between the intervention and caregivers' beliefs/knowledge. RESULTS:
      One hundred ten caregivers were in the historical control group and 112 in the
      intervention group. The intervention group had more mothers and the infants were
      younger. Controlling for these differences, intervention group caregivers were
      more likely to state they would take a break if frustrated with infant crying (OR
      3.10, 95% CI, 1.62-5.93), were more likely to state frustration caused infant
      shaking (OR 2.21, 95% CI, 1.20-4.20), and to state their knowledge of SBS was
      from hospital staff (OR 3.39, 95% CI, 1.61-4.20). CONCLUSION: This targeted
      postpartum intervention incorporated into newborn anticipatory guidance can
      influence caregivers' beliefs about infant crying and knowledge of SBS.

PMID- 21940234
TI  - Silencing of Notch3 Using shRNA driven by survivin promoter inhibits growth and
      promotes apoptosis of human T-cell acute lymphoblastic leukemia cells.
AB  - BACKGROUND: As a highly conserved system, the activation of the Notch pathway has
      been implicated in the tumorigenesis of various hematologic diseases, including
      leukemias, lymphomas, and multiple myeloma. The Notch3 receptor is frequently
      expressed in T-cell acute lymphoblastic leukemia (T-ALL). METHODS: To explore its
      possibility as a therapeutic target for T-ALL, we investigated the effect of
      Notch3 silencing on Jurkat and SupT1 cells using a novel tumor-specific short
      hairpin RNA (shRNA) driven by survivin promoters. RESULTS: We found that
      downregulated expression of Notch3 correlated with significant apoptosis and
      inhibition of proliferation. CONCLUSION: These facts suggest that downregulating
      expression of Notch3 could attenuate the Notch signaling activity in T-ALL. All
      these results indicate that inhibition of Notch3 expression can result in potent
      antitumor activity in T-ALL.

PMID- 21940235
TI  - Cutaneous and systemic plasmacytosis vs. cutaneous plasmacytic castleman disease:
      review and speculations about pathogenesis.
AB  - Cutaneous and systemic plasmacytosis (C/SP), human herpes virus-8 (HHV8),
      negative multicentric plasmacytic Castleman disease (MPCD), and idiopathic
      plasmacytic lymphadenopathy are polyclonal plasma cell proliferations of unknown
      etiology that predominantly affect Asian individuals. Herein, we present our
      experience with a Vietnamese man with typical C/SP limited to the skin but, after
      10 years, may have developed perirenal involvement, and with a white man with
      human immunodeficiency virus and HHV8 negative MPCD with involvement of skin,
      lymph nodes, and kidneys at presentation, and who later succumbed to gastric
      carcinoma. Based on a review of the literature, we suggest that C/SP, cutaneous
      MPCD, and idiopathic plasmacytic lymphadenopathy with skin involvement are part
      of a continuum rather than distinct entities and, as such, may be regarded as
      variants of HHV8-negative MPCD. Although the majority of patients with C/SP run a
      chronic benign course, special attention should be given to monitoring for
      pulmonary and renal involvement. We hypothesize that long-lived plasma cells
      originate and survive in the environment of the skin akin to other stromal
      "survival" niches due to the local production of interleukin 6 and that such
      patients might respond to agents that interfere with interleukin-6 activity.

PMID- 21940236
TI  - Colloid milium with amyloid deposition of cytokeratin: does colloid milium have
      an epidermal origin?

PMID- 21940237
TI  - Effects of Hydroxydecine((r)) (10-hydroxy-2-decenoic acid) on skin barrier
      structure and function in vitro and clinical efficacy in the treatment of UV
      induced xerosis.
AB  - 10-Hydroxy-2-decenoic acid, a natural fatty acid only found in royal jelly, may
      be of value in correcting skin barrier dysfunction. We evaluated the activity of
      Hydroxydecine((r)), its synthetic counterpart, in vitro on the regulation of
      epidermal differentiation markers, ex vivo on the inflammatory response and
      restoration of skin barrier function, and in vivo on UV-induced xerosis in
      healthy human volunteers. In cultured normal human keratinocytes,
      Hydroxydecine((r)) induced involucrin, transglutaminase-1 and filaggrin protein
      production. In topically Hydroxydecine((r))-treated skin equivalents,
      immunohistochemical analysis revealed an increase in involucrin, transglutaminase
      1 and filaggrin staining. In a model of thymic stromal lymphopoietin (TSLP)
      induced inflamed epidermis, a Hydroxydecine((r))-containing emulsion inhibited
      TSLP release. In a model of inflammation and barrier impairment involving human
      skin explants maintained alive, Hydroxydecine((r)) balm restored stratum corneum
      cohesion and significantly increased filaggrin expression, as shown by
      immunohistochemistry. It also decreased pro-inflammatory cytokine secretion (IL
      4, IL-5 and IL-13). In healthy volunteers with UV-induced xerosis, the hydration
      index increased by +28.8% (p<0.01) and +60.4% (p<0.001) after 7 and 21 days of
      treatment with Hydroxydecine((r)) cream, respectively. Hydroxydecine((r)) thus
      proved its efficacy in activating keratinocyte differentiation processes in
      vitro, restoring skin barrier function and reducing inflammation ex vivo, and
      hydrating dry skin in vivo.

PMID- 21940238
TI  - The hair growth promoting effect of 4-O-methylhonokiol.

PMID- 21940239
TI  - [Accuracy of intraoperative imprint cytology of sentinel lymph nodes in cT1
      infiltrating breast cancer].
AB  - Intraoperative examination of sentinel lymph nodes (SLN) in breast cancer can
      avoid a new surgical procedure in case of positive SLN, but its value, efficacy
      and the methods used are still controversial. The aim of our study was to
      evaluate the imprint cytology intraoperative method of SLN analysis performed at
      our institution. We did a retrospective study of the sentinel lymph node
      procedures performed during a period of 24  months on cT1N0 unifocal breast
      cancers. Intraoperative procedure was mainly by imprint cytology (touch prep). A
      SLN procedure was performed on 187 women with 360 SLN. Two hundred and seventy
      seven SLN among 156 women were analyzed intraoperatively by touch prep. 19/48
      positive SLN were detected by intraoperative touch prep (sensitivity 39.6%;
      specificity 100%; positive predictive value 100%; negative predictive value
      88.7%, accuracy 89.5%). False negative rate of cytological intraoperative
      examination of SLN was 11,2% by SLN and 18,3% by patient. By univariate analysis,
      this rate significantly increased with lymphovascular invasion, tumor size cT1b
      and c and histological SBR grade 2 or 3. By multivariate analysis, only
      lymphovascular invasion was a predictive factor of intraoperative touch prep
      failure (OR = 3.3; IC 1.3-8.4). Intraoperative imprint cytology of SLN in breast
      cancer is associated with a high rate of false negativity that questions its use
      in this setting.

PMID- 21940240
TI  - What do we know about needs for help after suicide in different parts of the
      world? A phenomenological perspective.
AB  - BACKGROUND: "A person's death is not only an ending: it is also a beginning - for
      the survivors. Indeed, in the case of suicide, the largest public health problem
      is neither the prevention of suicide (...), nor the management of attempts (...),
      but the alleviation of the effects of stress in the survivor-victims of suicidal
      deaths, whose lives are forever changed and who, over a period of years, numbers
      in the millions ..." (Edwin S. Shneidman, 1973). AIMS: As there is no doubt that
      suicide postvention should be given a more prominent position on the agenda than
      is presently the case, this paper explores what we now know about perceived needs
      for help on the part of suicide bereaved in different parts of the world.
      METHODS: A search of related literature in the field was undertaken using the
      PubMed/PsychInfo databases. In addition, professionals throughout the world
      working in the field of suicide postvention were invited to submit reports about
      suicide postvention measures or literature. RESULTS: Very little research was
      found that reflected the perceived needs for help on the part of the bereaved -
      and all the studies stemmed from countries in the Western world. However, the
      bereaved in these studies agreed about a common need for peer and social support,
      and that professional help must be adapted to and offered with respect for
      individual needs. Thus, it seems that in societies in which the stigma about
      suicide has diminished, the bereaved experience very similar needs for help,
      whereas in other societies it is difficult to talk about their need for help
      because of the sanctions and taboos connected to suicide. CONCLUSIONS: We need
      far more culturally sensitive research in order to explore and clarify how each
      community understands suicide and reacts to families who have lost someone by
      suicide.

PMID- 21940241
TI  - Predicting suicidal risk in a cohort of depressed children and adolescents.
AB  - BACKGROUND: In children and adolescents with a depressive disorder, predicting
      who will also go on to exhibit suicide-related behaviors (SRBs), including
      suicide attempt or self-harm, is a key challenge facing clinicians. AIMS: To
      investigate the relative contributions of depressive disorder severity,
      hopelessness, family dysfunction, and perceived social support to the risk of
      suicide-related behaviors. METHODS: This was a cross-sectional study of a group
      of 10-16-year-olds with major depressive disorders and dysthymic disorder.
      RESULTS: Child-rated depressive disorder symptom severity emerged as the greatest
      predictor of risk. Hopelessness and family dysfunction were also significant
      predictors of SRBs. In combination these variables were strong predictors,
      accounting for 66% of the variance. This is a cross-sectional study design,
      rather than longitudinal, therefore risk prediction over time was not possible.
      CONCLUSIONS: Understanding the child and adolescents depressive disorder symptom
      severity from their perspective, their level of hopelessness, as well as their
      family context is critical in understanding the risk of SRBs. These findings may
      help to provide direction for targeted interventions to address these clinical
      risk factors.

PMID- 21940242
TI  - Coping style as a mediator of the relationship between depressive symptoms and
      deliberate self-harm.
AB  - BACKGROUND: Deliberate self-harm (DSH) occurs with high frequency among clinical
      and nonclinical youth populations. Although depression has been consistently
      linked with the behavior, not all depressed individuals engage in DSH. AIMS: The
      current study examined maladaptive coping strategies (i.e., self-blame,
      distancing, and self-isolation) as mediators between depression and DSH among
      undergraduate students. METHODS: 202 students from undergraduate psychology
      courses at a private university in Southern California (77.7% women) completed
      anonymous self-report measures. RESULTS: A hierarchical regression model found no
      differences in DSH history across demographic variables. Among coping variables,
      self-isolation alone was significantly related to DSH. A full meditational model
      was supported: Depressive symptoms were significantly related to DSH, but adding
      self-isolation to the model rendered the relationship nonsignificant.
      LIMITATIONS: The cross-sectional study design prevents determination of whether a
      casual relation exists between self-isolation and DSH, and obscures the direction
      of that relationship. CONCLUSIONS: Results suggest targeting self-isolation as a
      means of DSH prevention and intervention among nonclinical, youth populations.

PMID- 21940243
TI  - Evaluation of the Commitment to Living (CTL) curriculum: a 3-hour training for
      mental health professionals to address suicide risk.
AB  - BACKGROUND: Finding effective and efficient options for training mental health
      professionals to assess and manage suicide risk is a high priority. AIMS: To test
      whether an innovative, brief workshop can improve provider knowledge, confidence,
      and written risk assessment in a multidisciplinary sample of ambulatory and acute
      services professionals and trainees. METHODS: We conducted a pre/post evaluation
      of a 3 h workshop designed to improve clinical competence in suicide risk
      assessment by using visual concept mapping, medical records documentation, and
      site-specific crisis response options. Participants (N = 338 diverse mental
      health professionals) completed pre- and postworkshop questionnaires measuring
      their knowledge and confidence. Before and after the workshop, participants
      completed documentation for a clinical vignette. Trained coders rated the quality
      of risk assessment formulation before and after training. RESULTS: Participants'
      knowledge, confidence, and objectively-rated documentation skills improved
      significantly (p < .001), with large effect sizes. Participants' expectation of
      their ability to transfer workshop content to their clinical practice was high
      (mean = 4.10 on 1-5 scale). CONCLUSIONS: Commitment to Living is a promising,
      innovative, and efficient curriculum for educating practicing clinicians to
      assess and respond to suicide risk. Well-designed, brief, suicide risk management
      programs can improve clinicians' knowledge, confidence, and skill.

PMID- 21940244
TI  - Caring Letters Project: a military suicide-prevention pilot program.
AB  - BACKGROUND: The Caring Letters Project (CLP) is a suicide prevention program that
      involves sending brief caring letters to discharged inpatients following
      psychiatric hospitalization. Several studies suggest that repeatedly sending
      caring messages may reduce suicides and suicide attempts in high-risk
      populations. AIMS: The aims of this study were to (1) evaluate feasibility of use
      in the military setting, (2) explore trends toward reduction of psychiatric
      rehospitalizations, (3) assess preference for and test e-mail correspondence, and
      (4) identify best practices and gather data to inform a randomized controlled
      study. METHODS: A total of 110 psychiatric inpatients at a military treatment
      facility consented, were interviewed, and then received personalized handwritten
      letters or e-mails at regular intervals following discharge. Data collected
      included demographics, clinical characteristics, preference for e-mail versus
      postal mail, rates of undeliverable and return correspondence,
      rehospitalizations, and adverse events requiring safety procedures. RESULTS: A
      total of 436 letters and e-mails have been sent to date. Most participants
      indicated preference for e-mail versus postal mail. Fifteen participants were
      readmitted for treatment compared to 20 patients in usual care. Twenty
      participants sent responses and all were positive statements about the program.
      There were no adverse events. CONCLUSIONS: This program is feasible for use at a
      military treatment facility. A randomized controlled trial is needed to determine
      whether the intervention can reduce suicide rates among military and veteran
      populations.

PMID- 21940245
TI  - The incidence of hospital-treated attempted suicide in Oviedo, Spain.
AB  - BACKGROUND: The incidence of hospital-treated attempted suicide has not been well
      established in Spain. AIMS: To determine the incidence of suicide attempters
      presenting to a hospital in Oviedo, Spain, to describe the nature of the suicidal
      behavior, and to identify sociodemographic subgroups of the population with high
      rates. METHODS: All admitted to the Hospital Universitario Central de Asturias,
      Oviedo, during the period 1 May 2008 to 30 April 2009 were examined and those
      meeting the internationally-recognized case definition were identified. RESULTS:
      A total of 308 suicide attempt presentations (39% male, 61% female) were made by
      279 individuals. Almost 90% of the suicide attempts involved a drug overdose. The
      age-adjusted total, male, and female attempted suicide rates were 83, 66, and 99
      per 100,000, respectively. The highest rate was among 35-44-year-olds for men and
      women (141.1 and 191.8 per 100,000, respectively). Incidence rates varied widely
      by sociodemographic characteristics with especially high rates among
      separated/divorced men (2.4%) and women (1.1%). CONCLUSIONS: The reported
      incidence of hospital-treated attempted suicide is below average in the European
      context but higher than that reported by previous Spanish studies. Persons
      separated or divorced constitute a high-risk group.

PMID- 21940246
TI  - Understanding the risks of recent discharge: the phenomenological lived
      experiences--"existential angst at the prospect of discharge".
AB  - BACKGROUND: Evidence indicates that people whose mental health problems lead them
      to require psychiatric hospitalization are at a significantly increased risk of
      suicide, and that the time immediately following discharge after such
      hospitalizations is a particularly high-risk time. AIMS: This paper reports on
      phenomenological findings from a federally funded, mixed-methods study that
      sought to better understand the observed increased risk for suicide following
      discharge from an inpatient psychiatric service. METHODS: A purposive sample of
      20 recently discharged former suicidal inpatients was obtained. Data were
      collected in hermeneutic interviews lasting between 1 h and 2 h and analyzed
      according to van (1997) interpretation of hermeneutic phenomenology. RESULTS: Two
      key themes, "existential angst at the prospect of discharge" and "trying to
      survive while living under the proverbial 'sword of Damocles'" were induced. Each
      of these was comprised of five themes with the first key theme (which is the
      focus of this paper) encompassing the following: "Feeling scared, anxious,
      fearful and/or stressed," "Preparedness," "Leaving the place of safety," "Duality
      and ambivalence," and "Feel like a burden." CONCLUSIONS: Early exploration of and
      reconciling of patients' expectations regarding inpatient care for their
      suicidality would be empirically based interventions that could diminish the
      postdischarge risk for further suicide attempts.

PMID- 21940247
TI  - Mapping suicide in London: a brief methodological case study on the application
      of the smoothing technique.
AB  - BACKGROUND: When one intends to globally smooth unstable rates, e.g., suicide
      rates in a region, one needs to consider whether it is better to smooth the rates
      toward the global mean of the country or toward the global mean of the same
      region. AIMS: The present study aims to provide a methodological framework to
      answer this question by smoothing suicide rates within London boroughs. METHODS:
      Based on the results of the spatial autocorrelation statistics, the noniterative
      empirical Bayes method of moments was chosen to globally smooth the suicide rate
      of each borough, first toward the global mean of England and Wales, and second
      toward the mean of the London region. RESULTS: The results revealed that
      smoothing the suicide rates of the boroughs toward the global mean of England and
      Wales had a stronger influence in reducing the variability of suicide rates than
      smoothing toward the global mean of the London region. CONCLUSIONS: Smoothing the
      rates toward the mean of a region within a country acts somewhat between global
      and local smoothing.

PMID- 21940248
TI  - The relationship between suicidal thinking and dating violence in a sample of
      adolescent abortion patients.
AB  - BACKGROUND: The relationship between suicidal thinking and adolescent dating
      violence has not been previously explored in a sample of adolescent abortion
      patients. AIMS: This paper highlights a study where the relationship between
      dating violence and severity of suicidal thinking was examined in a sample of 120
      young women ages 14-21 seeking to terminate an unintended pregnancy. METHODS: The
      Multidimensional Adolescent Assessment Scale and the Conflict in Adolescent
      Relationships Scale was used to gather information about psychosocial problems
      and dating violence so that the relationship between the two problems could be
      examined, while controlling for the other psychosocial problems. RESULTS: The
      results suggest that dating violence was related to severity of suicidal
      thinking, and that the magnitude of this relationship was moderated by the
      severity of problems with aggression. CONCLUSIONS: Specifically, as the severity
      of participant's general problems with aggression increased, the magnitude of the
      relationship between dating violence and severity of suicidal thinking increased.
      Limitations of the study and implications for practice are discussed.

PMID- 21940249
TI  - How Henry Hellyer's use of language foretold his suicide.
AB  - Henry Hellyer was an accomplished surveyor and explorer in Australia in the early
      1800s whose apparent suicide at the age of 42 has puzzled historians for
      generations. He left behind several written works, including letters, journals,
      and reports. AIMS: The current study assessed changes in the ways Hellyer used
      words in his various written documents during the last 7 years of his life.
      METHODS: Hellyer's writings were analyzed using the Linguistic Inquiry and Word
      Count program. RESULTS: Hellyer showed increases in first-person singular pronoun
      use, decreases in first-person plural pronoun use, and increases in negative
      emotion word use. As this is a single, uncontrolled case study, caution is
      recommended in generalizing from the current results. CONCLUSIONS: Results
      suggest Hellyer's increasing self-focused attention, social isolation, and
      negative emotion. Findings are consistent with increasing depression and suicidal
      ideation. Implications for using computerized text analysis to decode people's
      psychological states from their written records are discussed.

PMID- 21940250
TI  - Is the emotional response of survivors dependent on the consequences of the
      suicide and the support received?
AB  - BACKGROUND: Despite numerous studies that have assessed emotional reactions of
      people bereaved by suicide, many questions in this field are not yet clarified.
      AIMS: The purpose of the present study was to explore how emotional reactions of
      those bereaved by suicide depend on their gender, the relationship to the
      deceased, the consequences ("only negative," "negative and positive,"
      "predominantly positive") of the death for the bereaved and the professional
      support received. METHODS: The relationship between emotional reactions and
      characteristics was assessed in 163 suicide bereaved. Most bereaved, including
      all the parents of the suicide victims, had experienced emotions that occurred so
      often and so strongly that they had disturbed everyday life. The most frequently
      reported emotions were guilt and depressed mood. Female gender and being parents
      or spouses were associated with increased risk for lack of energy. Furthermore,
      the emotions of the bereaved depended on the consequences of the suicide and the
      professional support received. CONCLUSIONS: Professional support might be
      particularly important for suicide bereaved.

PMID- 21940251
TI  - A study of deliberate self-harm and its repetition among patients presenting to
      an emergency department.
AB  - BACKGROUND: Marked differences have been found in the characteristics of people
      dying by suicide in Western and Asian countries. However, there is less
      information available on possible differences for deliberate self-harm (DSH).
      AIMS: To compare the characteristics of people presenting to hospital in Hong
      Kong and Oxford (UK) with DSH, and to assess the outcome of those persons in Hong
      Kong. METHODS: A sample of DSH patients admitted to the accident and emergency
      (A&E) department of a regional hospital in Hong Kong was assessed and followed up
      6 months later to assess the risk of repetition of DSH, and was then compared
      with such patients in Oxford. RESULTS: The majority of patients in Hong Kong were
      female (male:female ratio of 1:2.4), young (59% were under 35), and had used self
      poisoning (78%). Over one-third were single (37%) and one-fourth unemployed
      (26%). About half (49%) scored in the high or very high categories of the Beck's
      Suicide Intent Scale, considerably more so than in Oxford; 44.6% of patients
      defaulted psychiatric outpatient service during the 6-month follow-up period. The
      repetition rate within the following 6 months was 16.7%. The number of self
      reported adverse life problems, history of childhood sexual and physical abuse,
      and repetitive self-mutilation were shown to be the factors most strongly
      correlated with the risk of re-attempt. Alcohol problems were much lower than in
      Oxford. CONCLUSIONS: The findings show that DSH patients in Hong Kong show some
      marked differences compared to those in Oxford. Implications for the prevention
      of repeated DSH in Hong Kong are discussed.

PMID- 21940252
TI  - Inequalities and impact of socioeconomic-cultural factors in suicide rates across
      Italy.
AB  - BACKGROUND: Suicide is a major cause of premature death in Italy and occurs at
      different rates in the various regions. AIMS: The aim of the present study was to
      provide a comprehensive overview of suicide in the Italian population aged 15
      years and older for the years 1980-2006. METHODS: Mortality data were extracted
      from the Italian Mortality Database. RESULTS: Mortality rates for suicide in
      Italy reached a peak in 1985 and declined thereafter. The different patterns
      observed by age and sex indicated that the decrease in the suicide rate in Italy
      was initially the result of declining rates in those aged 45+ while, from 1997
      on, the decrease was attributable principally to a reduction in suicide rates
      among the younger age groups. It was found that socioeconomic factors underlined
      major differences in the suicide rate across regions. CONCLUSIONS: The present
      study confirmed that suicide is a multifaceted phenomenon that may be determined
      by an array of factors. Suicide prevention should, therefore, be targeted to
      identifiable high-risk sociocultural groups in each country.

PMID- 21940253
TI  - The effects of situational obstacles and social support on suicide- prevention
      gatekeeper behaviors.
AB  - BACKGROUND: Although the effectiveness of suicide-prevention gatekeeper-training
      programs in improving knowledge, attitudes, and referral practices has been
      documented, their effects do not seem to be lasting. AIMS: This study
      investigated situational obstacles at work that prevent suicide-prevention
      gatekeepers from engaging in suicide-prevention behavior and the role of social
      support in modifying the relationship between situational obstacles and suicide
      prevention behaviors. METHODS: 193 gatekeepers completed an online survey to rate
      the obstacles they had experienced at work since completing a gatekeeper-training
      program and the support received from coworkers, supervisors, and the
      organization. Participants also reported the frequency of suicide-prevention
      behaviors performed. RESULTS: The results indicated that both situational
      obstacles and social support predicted the number of suicide-prevention behaviors
      performed, as expected. There was also a trend that support from supervisors and
      the organization may alleviate the adverse effect of situational obstacles on
      suicide-prevention behavior. LIMITATIONS: The cross-sectional nature of the study
      does not allow for directional, causal conclusions to be drawn. CONCLUSIONS: By
      understanding the roles of situational obstacles faced by trained gatekeepers at
      their work and the support they receive from supervisors and organizations,
      appropriate strategies can be identified and applied to facilitate gatekeeper
      performance.

PMID- 21940254
TI  - Interpersonal violence victimization and suicidal ideation. An examination in
      criminal offenders.
AB  - BACKGROUND: Offenders are at elevated risk for interpersonal violence
      victimization (IVV), which is a risk factor for suicide-related outcomes in some
      populations, suggesting the importance of examining risk associated with IVV in
      offenders. AIMS: The present study examined the association between IVV and
      suicidal ideation (SI) among criminal offenders in a pretrial jail diversion
      program in the United States. METHODS: 266 offenders were screened for ten common
      Axis I psychiatric disorders along with current SI and past-year IVV. RESULTS:
      Past-year IVV was significantly associated with current SI, and the association
      remained significant after adjusting for symptoms of ten Axis I psychiatric
      disorders, respectively and simultaneously. Gender did not moderate the IVV-SI
      association. CONCLUSIONS: The findings support a connection between IVV and SI in
      criminal offenders.

PMID- 21940255
TI  - Suicidal ideation, friendships with delinquents, social and parental
      connectedness, and differential associations by sex: findings among high-risk
      pre/early adolescent population.
AB  - BACKGROUND: The association between suicidal ideation, friendships with
      delinquents, and social/parental connectedness among pre/early adolescents who
      reside in high-risk communities is poorly understood. AIMS: This study examined
      among high-risk youths: (1) the association between suicidal ideation and having
      delinquent friends, school connectedness, social support, and different parenting
      styles (i.e., caring only, supervision only, caring with supervision); and, (2)
      the differential associations by sex. METHODS: The associations were assessed
      among 2,598 pre/early adolescents using logistic regression. The analyses were
      adjusted for demographic, mental distress, illicit substance use, and peer/date
      violence victimization factors. The interaction terms determined differences by
      sex. RESULTS: After adjusting for demographic factors and mental distress,
      suicidal ideation was positively associated with having delinquent friends;
      however, after factoring in illicit substance use and violence victimization,
      this association was negative for males. After adjusting for all factors,
      suicidal ideation was negatively associated with school connectedness and all
      parenting styles; however, the association between suicidal ideation and having
      parental caring with supervision was stronger for females. CONCLUSIONS: The
      results suggest the potential benefits of increasing school connectedness and
      improving parent-child interactions, particularly among females, and the
      potential benefits of violence and substance-abuse prevention strategies for
      youths, particularly males, connected with delinquent peers.

PMID- 21940256
TI  - Suicide attempts among depressed inpatients with depressive disorder in a
      Malaysian sample. Psychosocial and clinical risk factors.
AB  - BACKGROUND: Depressed inpatients constitute a high-risk population for suicide
      attempts. AIMS: To describe the interactions of clinical and psychosocial risk
      factors influencing suicide attempts among a Malaysian sample of depressed
      inpatients. METHODS: Seventy-five subjects were diagnosed with a depressive
      disorder according to the Structured Clinical Interview for DSM-IV Axis I
      Disorders-Clinical Version (SCID-CV). Data on suicide attempts, suicidal ideation
      (Scale for Suicidal Ideation, SSI), depression severity (Beck's Depression
      Inventory, BDI), recent life-event changes (Social Readjustment Rating Scale,
      SRRS), sociodemographic and other relevant clinical factors were collected.
      RESULTS: A third of the subjects presented after a current suicide attempt.
      Significant factors for a current suicide attempt were race, religion, recent
      life-event changes, suicidal ideation, and alcohol use disorder. Independent
      predictive risk factors for a current suicide attempt were Chinese race, recent
      marital separation, major mortgage or loans, and being newly diagnosed with
      depression. Any recent change in personal habits was shown to be a protective
      factor against current suicide attempt. Age and gender were nonsignificant
      factors. CONCLUSIONS: The findings are generally consistent with existing studies
      and highlight the role of psychosocial risk factors.

PMID- 21940257
TI  - Suicide announcement on Facebook.
AB  - BACKGROUND: The media and the Internet may be having an influence on suicidal
      behavior. Online social networks such as Facebook represent a new facet of global
      information transfer. The impact of these online social networks on suicidal
      behavior has not yet been evaluated. AIMS: To discuss potential effects of
      suicide notes on Facebook on suicide prevention and copycat suicides, and to
      create awareness among health care professionals. METHODS: We present a case
      involving a suicide note on Facebook and discuss potential consequences of this
      phenomenon based on literature found searching PubMed and Google. RESULTS: There
      are numerous reports of suicide notes on Facebook in the popular press, but none
      in the professional literature. Online social network users attempted to prevent
      planned suicides in several reported cases. To date there is no documented
      evidence of a copycat suicide, directly emulating a suicide announced on
      Facebook. CONCLUSIONS: Suicide notes on online social networks may allow for
      suicide prevention via the immediate intervention of other network users. But it
      is not yet clear to what extent suicide notes on online social networks actually
      induce copycat suicides. These effects deserve future evaluation and research.

PMID- 21940258
TI  - Understanding why older people develop a wish to die: a qualitative interview
      study.
AB  - BACKGROUND: Quantitative studies in several European countries showed that 10-20%
      of older people have or have had a wish to die. AIMS: To improve our
      understanding of why some older people develop a wish to die. METHODS: In-depth
      interviews with people with a wish to die (n = 31) were carried out. Through open
      coding and inductive analysis, we developed a conceptual framework to describe
      the development of death wishes. Respondents were selected from two cohort
      studies. RESULTS: The wish to die had either been triggered suddenly after
      traumatic life events or had developed gradually after a life full of adversity,
      as a consequence of aging or illness, or after recurring depression. The
      respondents were in a situation they considered unacceptable, yet they felt they
      had no control to change their situation and thus progressively "gave up" trying.
      Recurring themes included being widowed, feeling lonely, being a victim, being
      dependent, and wanting to be useful. Developing thoughts about death as a
      positive thing or a release from problems seemed to them like a way to reclaim
      control. CONCLUSIONS: People who wish to die originally develop thoughts about
      death as a positive solution to life events or to an adverse situation, and
      eventually reach a balance of the wish to live and to die.

PMID- 21940259
TI  - Does screening high school students for psychological distress, deliberate self
      harm, or suicidal ideation cause distress--and is it acceptable? An Australian
      based study.
AB  - BACKGROUND: Programs designed to detect students at risk of depression and
      suicidality have shown success (Shaffer et al., 2004). AIMS: The current study
      sought to examine whether or not such a program was acceptable to participants
      and whether or not it caused distress. METHODS: Participants were boys aged 14 to
      16. Participants were assessed using an on-line questionnaire; acceptability was
      measured via postal questionnaire. RESULTS: Of 272 participants, 31 (11.4%) were
      considered at-risk; 13 required ongoing support, 8 of whom had not previously
      sought help. Overall screening did not appear to cause significant undue
      distress, although some differences were evident between at-risk and not at-risk
      students. All participants found the program acceptable. CONCLUSIONS: When
      conducted carefully, early detection programs can be an effective and acceptable
      method of identifying at-risk adolescents.

PMID- 21940260
TI  - Wishes to die in older people: a quantitative study of prevalence and associated
      factors.
AB  - BACKGROUND: Death thoughts and wishes occur frequently among older people. In
      different European countries estimates of 10%-20% have been found. AIMS: To
      determine the prevalence and associated factors of death thoughts and wishes
      among older people in The Netherlands. METHODS: In The Netherlands 1794 people
      (58-98 years) were interviewed in 2005/2006 (Longitudinal Aging Study Amsterdam).
      RESULTS: 81.3% reported never having death thoughts/wishes; 15.3% reported having
      had such thoughts/wishes; 3.4% reported currently having a wish to die and/or a
      weakened wish to continue living. Of those with a current wish to die, 67% had
      depressive symptoms (vs. 32% of people with death thoughts/wishes ever and 9% of
      people who never had had death thoughts/wishes), and 20% suffered from a
      depressive disorder (vs. 5% if death thoughts/wishes ever; 0.3% if never death
      thoughts/wishes). In a multivariate analysis, a current wish to die was
      associated with having depressive symptoms, a depressive disorder, lower
      perceived mastery, financial problems, loneliness, small network, involuntary
      urine loss, being divorced, and having a speech impediment. CONCLUSIONS:
      Practical implications for health-care professionals are that they should be
      aware that in certain situations older people are more likely to develop a wish
      to die, and that a wish to die does not necessarily mean that someone has a
      depressive disorder. Nevertheless, it should serve as a trigger to investigate
      and to treat depression if present.

PMID- 21940261
TI  - Ultrastructure of liver progenitor/oval cells in children with nonalcoholic
      steatohepatitis.
AB  - PURPOSE: Very interesting reports have appeared lately on the role of liver
      progenitor/oval cells in the morphogenesis and development of nonalcoholic
      steatohepatits (NASH) in adult patients and experimental animals. However, no
      literature data concerning pediatric patients have been available. Therefore, the
      purpose of the study was to evaluate the ultrastructure of the population of
      liver progenitor/oval cells in the biopsy material from children with previously
      clinocopathologically diagnosed NASH. MATERIAL/METHODS: Electron-microscopic
      examinations were conducted on fresh tissue samples collected from 10 children
      with NASH (aged 2-14 years), which were fixed with a solution of 2%
      paraformaldehyde and 2.5% glutaraldehyde in 0.1 M cacodylate buffer. RESULTS:
      Ultrastructural examinations of the liver progenitor/oval cells in children with
      NASH show a quite prominent number of these cells, especially their two types,
      hepatic progenitor cells (HPCs) and intermediate hepatocyte-like cells (IHCs),
      with intermediate bile-like cells being the least frequent. They were found to
      occur single or in clusters of two, seldom of three, and frequently in the areas
      of advanced liver fibrosis or close to them. Many times, these cells were
      accompanied by hepatocytes showing a varying degree of death, to total cell
      disintegration. Interesting was the presence of activated nonparenchymal liver
      cells, i.e. Kupffer cells/macrophages and hepatic stellate cells, frequently
      found to adhere to the hepatic oval cells. CONCLUSIONS: The current study
      suggests a marked involvement of the population of liver progenitor/oval cells,
      mainly HPCs and IHCs, in the development of nonalcoholic steatohepatitis in
      pediatric patients, especially in fibrosis progression.

PMID- 21940262
TI  - Significance of ankle brachial index and collaterals for prediction of critical
      limb ischemia in infrainguinal peripheral arterial occlusive disease.
AB  - PURPOSE: Chronic limb ischemia (CLI) is a clinical diagnosis, but should be
      approved by technical tests like the ankle-brachial index (ABI). Although the ABI
      is well established, less is known about the influence of collateralization on
      clinical stage. MATERIAL/METHODS: Magnetic resonance angiographies (MRA) of 129
      lower extremities were searched for morphological changes and for the number of
      collateral vessels according to Sorlie. Ankle pressures were recorded as higher
      (APmax) and lower (APmin) systolic blood pressures of the two ankle arteries with
      consecutive calculation of ABImax and ABImin. RESULTS: In comparisons of ROC
      curves, APmax (AUC=0.749) did significantly better as a prognostic marker than
      APmin (AUC=0.642) (p=0.005) and ABImax (AUC=0.744) did significantly better than
      ABImin (AUC=0.650) (p=0.019). APmax showed a positive likelihood ratio (+LR) of
      5.79 and a negative likelihood ratio (-LR) of 0.47 (cutoff <=55 mmHg). For the
      number of collateral vessels a +LR 2.27 and a -LR of 0.09 and in patients with an
      APmax <=55 mmHg a +LR of 5.50 and a -LR of 0.00 were calculated (cutoff <=1
      collateral vessel). CONCLUSION: Whereas APmax is more eligible for verification
      of CLI, collateral count is better in exclusion of CLI. Both seem to be
      independent factors for validating the clinical diagnosis of CLI.

PMID- 21940263
TI  - New endodontic obturation systems and their interfacial bond strength with
      intraradicular dentine - ex vivo studies.
AB  - PURPOSE: To comparatively evaluate adhesive properties of selected root canal
      fillings through the measurement of the material-dentine interfacial bond
      strength. MATERIAL AND METHODS: Fifty extracted single-rooted human teeth with
      one canal each were prepared using Hero instruments to size 30.04. Teeth were
      divided into four subgroups depending on the root canal filling material and the
      method of obturation: Resilon/Epiphany - a thermoplastic method (IA),
      Resilon/Epiphany - a matching single-point method (IB), gutta-percha/Roeko Seal
      Automix - a thermoplastic method (IIA) and gutta-percha/Roeko Seal Automix - a
      matching single-point method (IIB). The obturated roots were cut perpendicular to
      the long axis to create 1.7 mm thick slices. The bond strength was measured for
      each test slice with push -out testing machine. RESULTS: The highest push-out
      bond strength was registered in subgroup IB (3.98 +/- 1.33 MPa). Significantly
      lower bond strength was observed in subgroups IA (0.50 +/- 0.24 MPa), IIA (0.33
      +/- 0.18 MPa) and IIB (0.08 +/- 0.03 MPa) (p<0.001). No statistically significant
      differences in material-dentine interfacial bond strength values were observed
      between IA and IIA, IA and IIB, IIA and IIB subgroups (p > 0.05). CONCLUSIONS:
      The push-out bond strength of the material-dentine interface was dependent on the
      type of material used and the root canal filling technique. The R/E system
      exhibited better adhesion ability to intraradicular dentine than G/RSA. The
      highest bond strength was observed for Resilon/Epiphany introduced with the
      single-cone technique.

PMID- 21940264
TI  - Platelet indices in SGA newborns.
AB  - PURPOSE: The current study objective was to compare blood platelet indices in
      full-term small-for-gestational-age newborns (SGA) and full-term appropriate-for
      gestational-age newborns (AGA). MATERIALS/METHODS: We introduced to our study 61
      SGA newborns (31 females and 30 males) and 70 eutrophic infants (32 females and
      38 males). The SGA newborns were divided into two groups: those weighing less
      than the 5th centile: 35 infants (16 females and 19 males) and those between the
      5th and 10th centiles: 26 infants (15 females and 11 males). Platelet indices
      were estimated in blood samples collected from the umbilical artery. RESULTS: SGA
      demonstrated a decreased count of blood platelets (238*103/MU) as compared with
      AGA (286*103/MUL), p=0.0001. Platelet hematocrit (PTC) also showed differences in
      both groups (SGA=0.19% vs. AGA=0.22%; p=0.0005). Mean platelet volume (MPV) was
      higher in SGA (8.25fl) as compared with AGA (7.84fl); p=0.008. Large platelet
      count (LPLT) was higher in AGA 6.26% vs. SGA=4.75%; p=0.01. Platelet distribution
      width (PDW) was found to be nearly the same (SGA=47%, AGA=46%). PDW was higher in
      SGA newborns < 5th centile (43%) as compared with SGA infants between the 5th and
      10th centiles (52%); p=0.008. CONCLUSIONS: A decreased blood platelet count,
      platelet hematocrit and large metabolically active platelet count, which in
      addition to reduced synthesis and excessive consumption of coagulation factors in
      states of hiperclotting is characteristic of IUGR, enhances the possibility of
      bleeding complications and increases the risk of infections. From a clinical
      point of view, it is important to take into consideration the degree of
      intrauterine hypotrophy during the evaluation of hemostatic disorders.

PMID- 21940265
TI  - Early and long-term prognosis of patients with coronary artery disease treated
      with percutaneous coronary interventions in 2005. Experience of single large
      volume PCI center.
AB  - PURPOSE: The progress which has been made in interventional cardiology
      contributes to the gradual improvement of the results of CHD (coronary heart
      disease) therapy. The aim of the study was the assessment of early and long-term
      prognosis in all the patients with CHD treated invasively in one large-volume PCI
      center in 2005. MATERIAL AND METHODS: 1390 consecutive patients with CHD treated
      with PCI in 2005 were included in the analysis. Patients with ST-elevation
      myocardial infarction (STEMI) accounted for 50% of cases, patients with stable
      angina (SA) amounted to 25%, and patients with non-ST elevation acute coronary
      syndromes (NSTE-ACS) constituted 25%. Mean follow-up was 738 (+/-237) days.
      RESULTS: The highest mortality during the hospitalization was noted within the
      STEMI group(SA vs. NSTE-ACS vs. STEMI; 0% vs. 0.3% vs. 4.1%, respectively;
      p<0.001). The highest mortality during a 2-year follow-up was also observed in
      the STEMI group (SA vs. NSTE-ACS vs. STEMI, 6.3% vs. 8.5% vs. 13.8%,
      respectively; p<0.001). Multiple regression model showed that independent risk
      factors for death during the follow-up were: age, glycaemia at admission, heart
      rate, blood pressure, ejection fraction, STEMI, ineffective PCI (R=0.3613;
      F(10.131)=19.672; p<0.0001 for the model). CONCLUSIONS: The highest relative
      increase of mortality after the discharge of patients with CHD undergoing PCI
      referred to the patients with NSTE-ACS. However, in the real life PCI practice
      STEMI patients have the worst hospital and long-term prognosis. Well recognized
      risk factors for death in patients with CHD are still of great importance in
      negative prognosis of patients undergoing PCI.

PMID- 21940266
TI  - Concomitant infections with human papillomavirus and various mycoplasma and
      ureaplasma species in women with abnormal cervical cytology.
AB  - PURPOSE: The objective of the present study is to verify possible association
      between infections with mycoplasmas and ureaplasmas and the presence of HPV
      infections in women diagnosed with abnormal cervical cytology. MATERIAL/METHODS:
      The investigation included 387 non-pregnant women among whom: 62 were diagnosed
      with ASCUS, 167 with LSIL, 27 with HSIL, 49 with cervical carcinomas, and 82
      females with normal cytology.The presence of HPV infection and identification of
      both ureaplasma and mycoplasma were confirmed by PCR using specific primers.
      RESULTS: HPV infections were demonstrated in 156 females (40%), with mycoplasmas
      and/or ureaplasmas were confirmed in 93 cases (24%). In HPV-positive patients,
      infections with mycoplasmas/ureaplasmas were more frequent, particularly for
      ureaplasmas (U. urealyticum p=0.004, U. parvum p=0.027). The percentage of
      females infected with U. urealyticum significantly increased in women diagnosed
      with cervical carcinoma as compared to controls.The statistical analysis
      demonstrated that the risk of HPV infection while already infected with any of
      the four analyzed species of Mycoplasmataceae increased two-fold. With
      concomitant of U. urealyticum infection, the risk of HPV infection was 4.7-fold
      greater than in the absence U. urealyticum infection. CONCLUSION: Since the
      presence of U. urealyticum associates significantly with the HPV infection,
      genotyping of the ureaplasma species should be recomended.

PMID- 21940267
TI  - Optimizing biliary stent patency by coating with hydrophobin alone or hydrophobin
      and antibiotics or heparin: an in vitro proof of principle study.
AB  - PURPOSE: Although a wide range of biliary plastic and metal stents is on offer
      nowadays, the ideal cost-effective stent that functions permanently and that is
      easy to handle regarding its exchange is still not available. Therefore we tested
      in an in vitro model if the coating of plastic stents with hydrophobin alone or
      with hydrophobin and antibiotics or heparin in combination leads to an inhibition
      of the clogging process. METHODS: We coated commercially available biliary
      plastic stents with hydrophobin alone, as well as with hydrophobin and
      antibiotics or heparin in combination. After an incubation period of 28 days in
      human bile, we examined the stents by scanning electron microscopy to see whether
      the clogging material on its surface was reduced. RESULTS: Coating of plastic
      stents with hydrophobin led to a reduction in the amount of adherent material on
      the surface of the stents. Coupling of ampicillin/sulbactam or levofloxacin did
      not lead to a further reduction of the clogging material, whereas coupling with
      highly concentrated heparin did reduce the adherent material. CONCLUSIONS: The
      coating of biliary plastic stents with hydrophobin or with hydrophobin and
      heparin in combination seems to be a promising option to delay the clogging
      process.

PMID- 21940268
TI  - Airway inflammation and eotaxin in exhaled breath condensate of patients with
      severe persistent allergic asthma during omalizumab therapy.
AB  - PURPOSE: The central role of IgE in allergic inflammation in asthma has provided
      a rationale for the development of omalizumab, the humanized monoclonal anti-IgE
      antibody. The aim of the study was to determine the effect of omalizumab
      treatment on changes in airway inflammatory process and eotaxin in exhaled breath
      condensate in patients with persistent severe allergic asthma. MATERIAL AND
      METHODS: The study was performed on a group of 19 patients with severe persistent
      allergic asthma treated with conventional therapy (according to GINA 2006) and
      with or without omalizumab (9 vs 10 patients). Eotaxin in exhaled breath
      condensate, exhaled nitric oxide, blood eosinophil count and serum ECP were
      measured before and after 16 weeks of therapy. RESULTS: In the group treated with
      omalizumab, a statistically significant decrease in the concentrations of eotaxin
      in EBC, FENO, serum ECP, and blood eosinophil count after 16 weeks of treatment
      was observed. Statistically significant correlations were revealed between the
      decrease in eotaxin and the decrease in FENO, serum ECP and blood eosinophil
      count after omalizumab therapy. CONCLUSIONS: Downregulation of eotaxin expression
      in the airways through limitation of eosinophilic inflammation could be essential
      in the beneficial effect of anti-IgE therapy with omalizumab in asthma patients.

PMID- 21940269
TI  - Can we expect progress in the treatment of fibrosis in the course of chronic
      pancreatitis?
AB  - Chronic pancreatitis (CP) is a necroinflammatory process characterized by loss of
      both exocrine and endocrine function. To date, the disease has been treated
      symptomatically. Real advances in CP management can be expected once the
      pathophysiology of the disease is elucidated and individual stages of its
      development are properly managed. A key role in the CP pathogenesis is played by
      activation of pancreatic stellate cells (PSCs) that cooperate with the remaining
      pancreatic cells. All these cells produce cytokines, growth factors, angiotensin
      and other substances, which paracrinally or autocrinally induce further,
      persistent activation of PSCs. The activated PSCs are capable of producing and
      modifying the extracellular matrix. An optimal therapeutic preparation should
      exert beneficial effects on all the above-mentioned phenomena observed in CP. The
      most promising treatment modalities include blocking of the renin-angiotensin
      system (RAS), activation of peroxisome proliferator-activated receptors gamma
      (PPAR-gamma), influence on the remaining PSC signaling pathways, blocking of
      substances produced by activated PSCs, and antioxidants. The findings of many
      recent experimental studies are highly encouraging; however, their efficacy
      should be confirmed in well-designed clinical trials.

PMID- 21940271
TI  - Treatment of chronic hepatitis C in a patient with Fanconi anaemia.
AB  - Fanconi anaemia is a rare autosomal recessive disorder with progressive bone
      marrow failure and predisposition to malignancy. We report a case of a 26-year
      old female patient with Fanconi anaemia and severe chronic active hepatitis C
      virus infection. Her past medical history included treatment with multiple blood
      transfusions and bone marrow transplantation at the age of 13. The decision to
      treat the infection was taken, and history of hematologic disease contributed to
      the introduction of therapy with leukocyte interferon-alpha n3 and ribavirin
      combined with a granulocyte - colony stimulating factor. The treatment was well
      tolerated and after 48 weeks a reduction of the viral load and alanine
      aminotransferase activity were achieved. No adverse effects on bone marrow
      functioning were noted.

PMID- 21940270
TI  - Resistance patterns and occurrence of virulence determinants among GRE strains in
      southwestern Poland.
AB  - PURPOSE: The aim of this study was to determine the antimicrobial resistance and
      the occurrence of virulence determinants among glycopeptide-resistant enterococci
      (GRE) isolated in 2007-2009 from patients hospitalized in southwestern Poland.
      MATERIAL AND METHODS: The minimal inhibitory concentrations (MICs) of antibiotics
      were determined by agar dilution method or by E-test(r). The presence of vanA -
      vanG resistance and virulence genes (agg, esp, gelE and cylA, cylB, cylM) was
      investigated using PCR. The ability to form biofilm and the activity of
      gelatinase, hemolysins, lipase and DNase were tested. RESULTS: All the GRE
      strains were susceptible to linezolid, daptomycin, and tigecycline and resistant
      to norfloxacin. In the Enterococcus faecium group, 17 strains carried the vanA
      gene and 20 the vanB gene. In the Enterococcu faecalis group, 4 strains carried
      the vanA gene and 1 the vanB gene. There were differences in tetracycline
      susceptibility between the VanA (70%) and the VanB (55%) phenotypes. Only
      linezolid had high activity against both the VanA and the VanB phenotypes. The
      esp gene was present in most of the GRE strains, but only 3 E. faecalis strains
      produced biofilm. Lipase was produced by 10/42 examined strains, gelatinase by
      4/42 and hemolysin by 3/42 isolates. CONCLUSIONS: Linezolid seems to be the
      optimal option in empirical therapy of infections caused by GRE strains because
      of the relationship between its activity (MIC value) and susceptibility
      breakpoint. There was no correlation between the prevalence of different
      virulence genes and resistance to the antibiotics tested.

PMID- 21940272
TI  - Visual vignette. Gastrinoma.

PMID- 21940273
TI  - Visual vignette. Anaplastic thyroid carcinoma.

PMID- 21940274
TI  - Visual vignette. Severe primary hyper- parathyroidism.

PMID- 21940275
TI  - Consequences of brand switches during the course of pediatric growth hormone
      treatment.
AB  - OBJECTIVE: To explore the effects of insurance-mandated brand switches during the
      course of pediatric recombinant human growth hormone (rhGH) treatment on clinical
      practice. METHODS: We e-mailed a 9-question, anonymous, Internet-based survey to
      active members of the Pediatric Endocrine Society. The survey consisted of
      multiple-choice and yes/no answers. Free-text comments were solicited for further
      explanation of responses. Quantitative answers were tabulated. Each investigator
      independently coded the free-text responses; themes based on codes identified by
      all 3 investigators in a minimum of 5 different respondents' comments were
      compiled and organized. RESULTS: Of the 812 active members of the Pediatric
      Endocrine Society who were e-mailed the survey, 231 responded. Two hundred eight
      respondents reported switching a patient's regimen from one rhGH product to
      another, and of these, 50% experienced repeated switches. Switches occurred for
      each commercially available rhGH brand. Frequent concerns noted by respondents
      involved dosing errors and treatment lapses from having to learn a new device and
      impaired adherence related to patient-family frustration and anxiety. Anti-GH
      antibodies, measured by only 3 endocrinologists when switching a patient's
      regimen from one brand to another, were negative before and after the product
      switch. When a patient switched rhGH brands, the most frequently reported time
      involvement for endocrine office staff was 2 hours for paperwork, 1 hour for
      device instruction, and 1 hour for "other" (mostly related to telephone
      reassurance). CONCLUSION: GH brand switches may adversely affect patient care and
      burden pediatric endocrinology practices.

PMID- 21940276
TI  - Severe hypercholesterolemia in patients with graft-vs-host disease affecting the
      liver after stem cell transplantation.
AB  - OBJECTIVE: To review the available literature on severe hypercholesterolemia
      occurring in the context of graft-vs-host disease affecting the liver. METHODS: A
      literature search was conducted in PubMed for articles on hypercholesterolemia
      occurring in the context of graft-vs-host disease after allogeneic hematopoietic
      stem cell transplantation. The review included the type of lipid abnormalities
      observed, complications, and available management strategies. RESULTS: Severe
      hypercholesterolemia can occur in patients who develop graft-vs-host disease
      after transplant. We describe 8 patients with severe hypercholesterolemia
      occurring in the context of graft-vs-host disease affecting the liver after
      hematopoietic stem cell transplantation (7 from the literature and 1 from our
      institution). No association was observed with a specific age, sex, type of
      hematologic malignancy, or use of a specific immunosuppressant. The elevated
      cholesterol is either due to high concentrations of lipoprotein X or low-density
      lipoprotein. Unlike low-density lipoprotein, lipoprotein X may not be
      atherogenic. CONCLUSIONS: Treatment may not be required when lipoprotein X is the
      major elevated lipoprotein unless hyperviscosity occurs, but treatment is
      indicated when there is elevation in low-density lipoprotein. Plasmapheresis may
      be necessary. Ultimate treatment is control of the graft-vs-host disease
      affecting the liver that would improve or completely resolve the hyperlipidemia.

PMID- 21940277
TI  - Autoimmune thyroid disease in patients with vitiligo: prevalence study in India.
AB  - OBJECTIVE: To identify the prevalence of autoimmune thyroid disease (AITD) in
      Asian Indian patients with vitiligo and to compare the clinical profile between
      thyroid peroxidase (TPO) antibody-positive and TPO antibody-negative groups.
      METHODS: In this cross-sectional, case-controlled study, 50 patients with
      vitiligo (29 women and 21 men) were included. Patients with previous disorders,
      irradiation, or surgical procedures involving the thyroid were excluded from the
      study. All participants underwent a complete physical examination, and a single
      fasting blood sample was analyzed for thyroid function (triiodothyronine,
      thyroxine, thyroid-stimulating hormone, and TPO and thyroglobulin antibodies),
      inflammatory and immunologic markers (erythrocyte sedimentation rate, C-reactive
      protein, and rheumatoid factor), and serum calcium, phosphorus, and alkaline
      phosphatase concentrations. All patients underwent thyroid ultrasonography, and
      the data were analyzed by appropriate statistical methods. RESULTS: The mean age
      of the study participants was 42.7 +/- 17 years, and 14 of 50 patients (28%) had
      TPO antibody positivity. A goiter was present in 11 of 50 patients, and the
      thyroid volume by ultrasonography was similar between the 2 groups. Subclinical
      hypothyroidism was found in 14 of 50 patients (28%) but more frequently in the
      TPO antibody-positive group (8 of 14 or 57%) than in the TPO antibody-negative
      group (6 of 36 or 17%). The prevalence of AITD was 20 of 50 patients (40%) when
      the TPO antibody-positive group and those with subclinical hypothyroidism were
      considered collectively. None of the patients had overt hypothyroidism or
      hyperthyroidism. All other clinical, biochemical, and inflammatory variables did
      not differ significantly between the TPO antibody-positive and antibody-negative
      groups. CONCLUSION: Our data showed a 40% prevalence of thyroid disease in
      patients with vitiligo in India. The risk is exacerbated in patients with thyroid
      autoimmunity; thus, regular screening of patients with vitiligo for AITD is
      needed.

PMID- 21940278
TI  - Coexistence of tumor-induced osteomalacia and primary hyperparathyroidism.
AB  - OBJECTIVE: To present an unusual case of coexisting tumor-induced osteomalacia
      (TIO) and primary hyperparathyroidism (PHPT). METHODS: We report the clinical
      features, imaging studies, and the results of laboratory investigations before
      and after surgical resection of both a soft-tissue tumor and a parathyroid
      adenoma. RESULTS: A 44-year-old woman was referred to the endocrinology
      department with a diagnosis of PHPT accompanied by unusually severe
      hypophosphatemia, despite having received treatment with cinacalcet. Debilitating
      muscle weakness and bone pain, severe phosphaturia and hypophosphatemia,
      inappropriately normal calcitriol, and elevated fibroblast growth factor-23 and
      intact parathyroid hormone levels raised the suspicion of coexisting TIO and
      PHPT. Imaging studies were negative, but histologic characteristics of a palpable
      subcutaneous mass from the patient's thigh revealed a phosphaturic mesenchymal
      tumor. Complete remission after surgical removal of both the soft-tissue tumor
      and the parathyroid adenoma confirmed the diagnosis. CONCLUSION: The coexistence
      of TIO and PHPT has not been described before and can cause life-threatening
      hypophosphatemia. Diagnosis and localization of the tumor is of paramount
      importance since surgery is the treatment of choice for both TIO and PHPT.

PMID- 21940279
TI  - Vitamin D insufficiency in diabetic retinopathy.
AB  - OBJECTIVE: To assess the relationship between vitamin D status and diabetic
      retinopathy. METHODS: A clinic-based, cross-sectional study was conducted at
      Emory University, Atlanta, Georgia. Overall, 221 patients were classified into 5
      groups based on diabetes status and retinopathy findings: no diabetes or ocular
      disease (n = 47), no diabetes with ocular disease (n = 51), diabetes with no
      background diabetic retinopathy (n = 41), nonproliferative diabetic retinopathy
      (n = 40), and proliferative diabetic retinopathy (PDR) (n = 42). Patients with
      type 1 diabetes and those taking >1,000 IU of vitamin D daily were excluded from
      the analyses. Study subjects underwent dilated funduscopic examination and were
      tested for hemoglobin A1c, serum creatinine, and 25-hydroxyvitamin D [25(OH)D]
      levels between December 2009 and March 2010. RESULTS: Among the study groups,
      there was no statistically significant difference in age, race, sex, or
      multivitamin use. Patients with diabetes had lower 25(OH)D levels than did those
      without diabetes (22.9 ng/mL versus 30.3 ng/mL, respectively; P<.001). The mean
      25(OH)D levels, stratified by group, were as follows: no diabetes or ocular
      disease = 31.9 ng/mL; no diabetes with ocular disease = 28.8 ng/mL; no background
      diabetic retinopathy = 24.3 ng/mL; nonproliferative diabetic retinopathy = 23.6
      ng/mL; and PDR = 21.1 ng/mL. Univariate analysis of the 25(OH)D levels
      demonstrated statistically significant differences on the basis of study groups,
      race, body mass index, multivitamin use, hemoglobin A1c, serum creatinine level,
      and estimated glomerular filtration rate. In a multivariate linear regression
      model with all potential confounders, only multivitamin use remained significant
      (P<.001). CONCLUSION: This study suggests that patients with diabetes, especially
      those with PDR, have lower 25(OH)D levels than those without diabetes.

PMID- 21940280
TI  - Successful management of differentiated thyroid cancer in a community-based
      endocrine practice.
AB  - OBJECTIVE: To describe the range of differentiated thyroid cancer (DTC) cases,
      disease complexity, and treatment outcomes seen in our 3-physician community
      based general endocrine practice during an 8-year period in order to make
      comparisons with published cohorts from university settings. METHODS: Medical
      records of patients with DTC treated between 2002 and 2009 at Mountain Diabetes
      and Endocrine Center (Asheville, North Carolina) were reviewed. Pathologic
      features, staging, and disease status at last contact were determined.
      Multivariate analyses of adverse prognostic risk factors at diagnosis,
      recombinant human thyroid-stimulating hormone use, and radioiodine use were
      compared with the ultimate outcome of patients. RESULTS: We treated a total of
      167 patients with DTC during the study period (mean age at diagnosis, 44.4 years;
      mean duration of follow-up, 6.2 years). In our study cohort, 88.6% had papillary
      thyroid cancer, 74% had stage I disease, and 32.4% of those with papillary
      thyroid cancer had microscopic tumors (<=1 cm). Remission occurred in 67.1%,
      17.1% had persistent disease, and 11.8% were indeterminate for remission; non
      thyroid cancer death occurred in 2.6% and disease-specific death in 1.3%. The
      mean number of adverse prognostic risk factors per patient was 2.0 in those with
      remission and 4.7 in those with persistent disease. CONCLUSION: Community-based
      endocrinologists evaluate the full spectrum of thyroid cancer disease complexity
      and can achieve excellent outcomes. In our current study group, disease
      persistence and disease-specific death occurred in 17.1% and 1.3%, respectively.
      Individualization of care based on prognostic variables guided our diagnostic and
      therapeutic decisions.

PMID- 21940281
TI  - Hyalinizing trabecular tumor in a background of lymphocytic thyroiditis: a
      challenging neoplasm of the thyroid.
AB  - OBJECTIVE: To describe a case of hyalinizing trabecular tumor (HTT) in a
      background of lymphocytic thyroiditis that was misdiagnosed as papillary thyroid
      carcinoma (PTC) based on fine-needle aspiration (FNA) cytologic findings and
      overtreated with total thyroidectomy. METHODS: We present a case report,
      including the imaging and pathologic findings, of a 68-year-old woman who
      presented with a multinodular goiter that was suspicious for PTC. RESULTS: On the
      basis of FNA cytologic findings, she underwent a total thyroidectomy, and
      histologic examination of the thyroid gland revealed HTT in a background of
      lymphocytic thyroiditis. Radioiodine treatment was not administered because of
      the tumor's low risk profile. No metastatic foci were established under
      nonsuppressive levothyroxine therapy after 3 years of follow-up. CONCLUSIONS: HTT
      is a challenging entity because of the uncertainty of its nature, the diagnostic
      challenges, and the mimicry of other types of thyroid tumors. In order to avoid
      overtreatment, endocrinologists and thyroid surgeons should be aware of the
      features of HTT, and suspicious cases should be evaluated by experienced
      cytopathologists.

PMID- 21940282
TI  - Glucagon responses of isolated alpha cells to glucose, insulin, somatostatin, and
      leptin.
AB  - OBJECTIVE: To determine whether glucagon suppression by leptin represents a
      direct effect on alpha cells rather than an indirect effect mediated via the
      hypothalamus. METHODS: We devised an in vitro alpha-cell suppression assay in
      cultured hamster InR1G9 cells. InR1G9 hamster cells were infected with adenovirus
      containing mouse leptin receptors, and they were then incubated with leptin,
      insulin, or somatostatin in concentrations known to suppress glucagon in vivo.
      RESULTS: Whereas somatostatin and insulin both suppressed the increase in
      glucagon secretion stimulated by high levels of glucose, leptin had no such
      effect. This inability of leptin to suppress glucagon in vitro could signify that
      it acts indirectly by causing the release of glucagon-suppressing peptides from
      the hypothalamus or stomach. To search for such a peptide, we studied the effects
      on glucagon secretion of 6 neuropeptides: orexin, melanocyte-stimulating hormone,
      neuropeptide Y, cocaine and amphetamine regulated transcript, neurotensin, and
      Agouti-related peptide that might be involved in the hypothalamic action of
      leptin. None of these peptides suppressed glucagon at low, normal, or elevated
      glucose concentrations. CONCLUSIONS: If the cultured alpha cells used faithfully
      mimic the leptin response of in situ alpha cells of the diabetic animal, the
      glucagon-suppressing action of leptin is indirect, but is not mediated by any 1
      of the 6 neuropeptides tested.

PMID- 21940283
TI  - Effect of metformin therapy on vitamin D and vitamin B12 levels in patients with
      type 2 diabetes mellitus.
AB  - OBJECTIVE: To determine the effect of metformin on 25-hydroxyvitamin D [25(OH)D]
      and vitamin B12 levels in patients with type 2 diabetes mellitus. METHODS: We
      performed a retrospective review of medical records of patients treated between
      2003 and 2009 at Loyola University Medical Center, Maywood, Illinois, in both
      ambulatory primary care and endocrinology clinics. The study cohort consisted of
      706 patients with type 2 diabetes mellitus who were 20 to 93 years old (mean age,
      63 +/- 13) and had a mean body mass index of 33.1 kg/m2. Of these patients, 42%
      were treated with metformin, and 34% had been diagnosed with osteoporosis or
      osteopenia. RESULTS: Patients taking metformin had statistically significant
      lower vitamin B12 levels than those not receiving metformin (P<.0001; 95%
      confidence interval [CI] = -220 to -84 pg/mL). No statistically significant
      difference was found between users and nonusers of metformin in regard to 25(OH)D
      levels when adjusted for variables (P = .297; 95% CI for mean difference = -0.7
      to 2.2 ng/mL). Metformin use did not adversely affect successful treatment of
      vitamin D deficiency in this patient population as a whole, nor did it affect the
      subgroup with osteoporosis (P = .956). The patients with osteoporosis had
      statistically significant lower baseline 25(OH)D levels in comparison with those
      without osteoporosis, when adjustments were made for all variables (P = .003; 95%
      CI = 0.7 to 3.5 ng/mL). CONCLUSION: This study confirms the higher prevalence of
      vitamin B12 deficiency in metformin-treated patients with type 2 diabetes than in
      those not treated with metformin. This study also suggests that vitamin D
      deficiency is not a clinical concern among metformin-treated patients with type 2
      diabetes and that metformin does not negatively affect treatment of vitamin D
      deficiency in these patients.

PMID- 21940284
TI  - What if many follicular variant papillary thyroid carcinomas are not malignant? A
      review of follicular variant papillary thyroid carcinoma and a proposal for a new
      classification.
AB  - OBJECTIVES: To review the relevant literature concerning follicular variant of
      papillary thyroid carcinoma (FVPTC) with an emphasis on the heterogeneity of this
      disorder and to propose a new classification for FVPTC on the basis of molecular
      diagnostics and apply the classification to a typical case. METHODS: English
      language articles pertaining to FVPTC published between January 1990 and December
      2010 were reviewed. RESULTS: FVPTC is particularly vexing. The criteria for
      diagnosing FVPTC appear to have changed over the years. Pathologists often
      disagree about the diagnosis of FVPTC. The clinical behavior of these tumors is
      variable. Molecular diagnostic studies suggest that FVPTC represents a
      heterogeneous group of disorders rather than a single entity. CONCLUSIONS: On the
      basis of the available data, it is proposed that individual cases of FVPTC be
      reclassified as papillary thyroid carcinoma, follicular thyroid carcinoma, or
      follicular adenomas, after appropriate molecular biologic studies have been
      completed. Long-term follow-up studies to validate this classification are
      necessary.

PMID- 21940285
TI  - Evaluation of myocardial iron overload using cardiovascular magnetic resonance
      imaging.

PMID- 21940286
TI  - The role of dietary and socioeconomic status assessment on the predictive ability
      of the HellenicSCORE.
AB  - INTRODUCTION: The optimal performance of cardiovascular disease (CVD) risk models
      in various populations (such as the Framingham Heart Sheet or the ESC SCORE) is
      of major interest in risk prediction modeling nowadays. We evaluated whether the
      inclusion of socioeconomic status (SES) in the HellenicSCORE would increase the
      accuracy of prediction, irrespectively of dietary information and the classical
      CVD risk factors. METHODS: Data from 1514 men and 1528 women (age >18 years), who
      were free of known CVD on enrolment in 2001-02, were studied (the ATTICA study).
      Five years later a follow up was performed and the development of CVD was defined
      (WHO-ICD-10 criteria). As SES indicators, education status and mean annual income
      were recorded, and a special SES 3-class index was calculated (low, moderate and
      high). The MedDietScore, which incorporates the inherent characteristics of the
      Mediterranean diet, was used as a dietary assessment tool, while the
      HellenicSCORE, which reflects the level of CVD risk factors, was also calculated.
      Additive logistic regression models were used to test the additive effect of SES
      and dietary assessment on the predictive ability of the HellenicSCORE. RESULTS:
      SES assessment did not improve the predictive ability of the estimated risk model
      compared to the model that included the HellenicSCORE, physical activity status,
      waist-to-hip ratio, diabetes and family history of CVD. Additionally, SES did not
      improve the predictive ability of the estimated risk model even when dietary
      assessment was added to the above model. CONCLUSIONS: Socioeconomic status does
      not improve the predictive ability of a CVD risk model, even when dietary
      information is also taken into account.

PMID- 21940287
TI  - The use of rotational atherectomy and drug-eluting stents in the treatment of
      heavily calcified coronary lesions.
AB  - INTRODUCTION: The treatment of calcified coronary artery lesions is a challenge
      for percutaneous angioplasty. Rotational atherectomy is an established technique
      for the effective modification of these lesions prior to conventional angioplasty
      and stent implantation. Drug-eluting stents (DES) have shown encouraging results
      in complex lesions and high-risk patients. METHODS: This retrospective study
      investigated the immediate and long-term prognosis after treatment with
      rotational atherectomy (RotA) and DES implantation in 184 patients with calcified
      coronary artery lesions. RESULTS: During follow up (mean 49 months), 7 patients
      died (1 from a non-cardiac cause) and the incidence of major adverse cardiac
      events was 14.85%. Only 4.15% of patients underwent a new angioplasty procedure.
      CONCLUSIONS: The combination of RotA and DES in calcified coronary artery lesions
      has a very good angiographic result and a satisfactory clinical outcome.

PMID- 21940288
TI  - Quality of life measurement in patients with hypertension in Cyprus.
AB  - INTRODUCTION: Cardiovascular diseases and hypertension may have a significant
      impact on the quality of life of those who suffer from these conditions. The aim
      of the present study was to measure health-related quality of life among Cypriot
      patients suffering from hypertension and/or dyslipidaemia, as well as to
      investigate any temporal changes in their quality of life at 3 and 6 months from
      the initial visit. METHODS: A stratified random sampling method was used in this
      follow-up multi-centre study to select a representative sample of physicians who
      treat patients with hypertension in both public and private sector outpatient
      hospital clinics and physician offices. The participants were diagnosed by the
      physician according to the 2007 European guidelines for the management of
      arterial hypertension. The EQ-5D questionnaire was employed to measure self
      assessed quality of life among these patients. Six hundred and fifty-four
      patients were recruited by physicians and agreed to participate, while 528 of
      them successfully completed EQ-5D at baseline and two subsequent phases (at 3 and
      6 months), representing a response rate of 80.7%. RESULTS: A total of 39.6% of
      the respondents reported problems in one or more of the EQ-5D dimensions. This
      was more apparent in the case of anxiety and depression. There appeared to be
      statistically significant improvements with regard to mobility, usual activities,
      pain/discomfort and anxiety/depression dimensions between the initial visit and
      on first follow up, as well as subsequently. Median (interquartile range) EQ-5D
      index scores were 0.97 (0.19), 0.97 (0.19) and 0.97 (0.17) at first visit, first
      follow-up and second followup respectively (p<0.001). Also, median EQ-5D VAS
      scores were 80 (20), 85 (10) and 90 (15) at the initial, first follow-up and
      second follow-up visit respectively (p<0.001). Median EQ-5D VAS scores increased
      over time amongst all socio-demographic and risk groups of participants.
      CONCLUSION: Hypertension had little association with mobility and physical
      activities, indicating that performing physical activities was not limited by
      hypertension. However, hypertension seems to be more strongly related to anxiety
      and depression.

PMID- 21940290
TI  - Methods and indications for ablation of ventricular tachycardia.

PMID- 21940289
TI  - Fluid dynamic aspects of ejection in hypertrophic cardiomyopathy.

PMID- 21940291
TI  - Current concerns and difficulties in the prevention of cardiovascular diseases.

PMID- 21940292
TI  - Three dimensional trans-esophageal echocardiography for the evaluation of flail
      mitral valve.

PMID- 21940293
TI  - Aortic root replacement in case of isolated aortitis and previous coronary artery
      bypass.
AB  - The surgical management of aortic regurgitation in a patient with aortitis is
      potentially of high risk, especially if it is a reoperation. We present the case
      of a 59-year-old man for whom coronary artery bypass surgery was not feasible due
      to structural abnormalities of the aorta and hybrid management was applied. The
      histopathological examination showed aortitis. One year later, the same patient
      developed severe aortic regurgitation. In order to minimize the surgical risk of
      the reoperation we considered all the surgical options. The modified Bentall
      procedure still seems to be the gold standard in these cases.

PMID- 21940294
TI  - Pericardial effusion in a young patient with newly diagnosed systemic lupus
      erythematosus and a mediastinal mass.
AB  - We present the case of a 32-year-old-woman who was admitted to the hospital for
      evaluation of pericardial effusion. The subsequent diagnostic workup revealed the
      presence of a mediastinal mass along with systemic lupus erythematosus (SLE). The
      patient underwent thymectomy, and histological evaluation of the resected mass
      revealed thymic follicular hyperplasia without evidence of malignancy. SLE
      disease activity was promptly controlled by corticoids. Clinicians should be
      aware of the occasional association of autoimmune disorders with focal thymic
      hyperplasia, which might be confused with thymomas or thymocarcinomas.

PMID- 21940295
TI  - Arrhythmogenic right ventricular cardiomyopathy/dysplasia.
AB  - We describe the case of a 51-year-old woman with a 10-year history of dyspnoea
      and fatigue on slight effort, presyncopal episodes, and ventricular extrasystolic
      arrhythmia. Tests were negative for coronary artery disease, valvular disease, or
      left ventricular dysfunction. The patient fulfilled the clinical criteria for
      arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) and the
      diagnosis was confirmed histologically with an endomyocardial biopsy. During 5
      year follow up she also exhibited significant structural progression to the left
      ventricle. This is a rare case of ARVC/D manifested in middle age, with a
      negative family history, negative test for desmosome mutations, and negative
      myocardial immunohistochemical analysis, evidence that tends to suggest an
      acquired form of the disease. We also present a brief review of the clinical,
      electrocardiographic, structural, pathological/anatomical and genetic
      characteristics of the disease, the diagnostic criteria, prognosis, management,
      and sudden death prevention, as well as the way we have managed our patient until
      the present day.

PMID- 21940296
TI  - A giant, free-floating mass in the left atrium in a patient with atrial
      fibrillation.
AB  - A large intracardiac mass is a rare condition and one with an extremely high risk
      of haemodynamic and embolic complications. Urgent surgical excision is the
      treatment of choice, and the histological examination reveals the exact nature of
      the mass, usually a myxoma or a thrombus. We present the case of an 80-year-old
      woman, with a history of atrial fibrillation, who was admitted because of a
      seriously impaired level of consciousness, and fever. A large cerebral infarct
      and a urinary tract infarction were diagnosed. On the transthoracic
      echocardiogram a giant, free-floating mass was detected in the left atrium,
      transiently obstructing the mitral valve orifice. Based on the features of the
      mass and patient's history, it was considered more likely to be a thrombus rather
      than a tumour. Given the patient's extremely unfavourable neurological status,
      cardiac surgery was considered to be contraindicated and the patient was
      administered unfractionated heparin intravenously. Unfortunately, after a few
      hours the patient suffered a cardiac arrest and died.

PMID- 21940297
TI  - Multiple cerebral mycotic aneurysms due to left atrial myxoma: are there any
      pitfalls for the cardiac surgeon?
AB  - Acute cerebral embolism or cerebral aneurysm formation as a consequence of left
      atrial myxomas has been well documented, but the formation of multiple cerebral
      aneurysms resulting from atrial myxoma is a very rare neurological complication.
      We present the case of a 72-year-old-woman with a cardiac myxoma who suffered
      multiple cerebral mycotic aneurysms. After experiencing both vertigo and a sudden
      collapse accompanied by loss of consciousness, she underwent cerebral computed
      tomography (CT) and magnetic resonance imaging (MRI) examinations, which revealed
      multiple cerebral mycotic aneurysms of various dimensions and a large cyst, as a
      result of a previous haemorrhage. Embolisation was performed in large aneurysms
      of the circle of Willis but not in the one located in the periphery, and re
      examination for a cardiac intervention a month later was indicated. The risk of
      cerebral haemorrhage was considered high; thus she was not operated on.
      Conservative treatment followed. Two years after the first diagnosis the patient
      remains healthy, suggesting that in such cases we should also consider
      conservative treatment. According to the literature, the risk is high when
      aneurysms are large, multiple and intractable. We propose that cerebral CT or MRI
      scan should be performed before operation in all patients with a cardiac myxoma,
      especially in those with left cardiac chamber localisation.

PMID- 21940298
TI  - An unusual combination of congenital anomalies in an adult patient: patent ductus
      arteriosus, Kommerell's diverticulum with aberrant right subclavian artery, and
      heterotaxy syndrome.
AB  - The heterotaxy syndrome is a rare and sporadic disorder. This syndrome presents
      with situs ambiguus, splenic malformations such as asplenia or polysplenia, and
      congenital heart disease. Congenital heart diseases associated with this syndrome
      include a broad variety of manifestations. Patent ductus arteriosus is one of
      them and percutaneous transcatheter closure can be challenging in the setting of
      this syndrome. Kommerell's diverticulum is a saccular aneurysmal dilation at the
      origin of an aberrant subclavian artery, and can be related with other congenital
      anomalies. However, there is no previous report of Kommerell's diverticulum being
      found together with patent ductus arteriosus and heterotaxy syndrome.

PMID- 21940299
TI  - Are general blood pressure targets still valid?

PMID- 21940300
TI  - Single right coronary artery.

PMID- 21940301
TI  - Treating heart failure in adults with congenital heart disease: lessons from the
      left ventricle.

PMID- 21940302
TI  - Unveiling the secrets of longevity: the Ikaria study.

PMID- 21940303
TI  - Establishment of a PDTT xenograft model of gastric carcinoma and its application
      in personalized therapeutic regimen selection.
AB  - BACKGROUND/AIMS: Lack of appropriate tumor models that reliably predict response
      to anticancer agents remains a major deficiency in the clinical practice of
      personalized cancer therapy. The aim of our study was to establish a patient
      derived tumor tissue (PDTT) xenograft model of gastric carcinoma for personalized
      cancer therapeutic regimen selection and testing of novel molecularly targeted
      agents. METHODOLOGY: Patient-derived tumor tissue of primary gastric carcinoma
      was used to create the xenograft model. After 11 weeks, xenografts were harvested
      for serial transplantation. H&E staining, immunohistochemical staining and
      Western blotting were used to determine biological stability of the xenograft
      during serial transplantation compared with the original tumor tissue. Drug
      sensitivities of the xenograft to bevacizumab (Avastin), FP3 and cetuximab were
      evaluated.

PMID- 21940304
TI  - Live surgery and teleconferencing at the 19th World Congress of the International
      Association of Surgeons, Gastroenterologists and Oncologists (IASGO) in Beijing.
AB  - Advanced technologies were introduced for the first time at the 19th World
      Congress of the Inter-national Association of Surgeons, Gastroenterologists and
      Oncologists (IASGO) in Beijing, China. Live surgery and multi-station
      teleconferencing were performed using the super high-speed inter-net to transmit
      and preserve the high quality life- like images of surgical operations. This is
      the first time in the history of IASGO that use has been made of this worldwide
      academic network and user friendly digital video transport system, which has many
      advantages over traditional telemedicine systems. Here we briefly report these
      epoch-making sessions and their future expectations

PMID- 21940305
TI  - Sequential evaluations of trace elements in patients receiving parenteral
      nutrition.
AB  - BACKGROUND/AIMS: To evaluate alterations of serum trace element (TE) levels in
      critically ill patients receiving parenteral nutrition (PN) including the
      recommended doses of TEs. METHODOLOGY: Measurements of serum levels of TEs such
      as zinc, iron, copper, manganese and iodine were performed on the day before, and
      two and four weeks after, administration of PN. RESULTS: Forty-six patients who
      received PN from October 2007 to August 2009, were enrolled. All patients
      received 100umol (6.5mg) zinc, 35umol (2mg) iron, 5umol (0.3mg) copper, 1umol
      (0.05mg) manganese and 1umol (0.13mg) iodine as the recommended daily doses.
      There were no significant differences in the serum levels of iron, copper and
      manganese among the three measurement points. On the other hand, there were
      significant differences in the serum levels of zinc (p<0.001), triiodothyronine
      (T3) (p=0.010) and unbound T3 (p=0.006) among the three points, but not for
      thyroxine (T4) and unbound T4. CONCLUSIONS: The recommended doses of TEs are
      justified for critically ill patients in terms of constant serum levels, except
      for zinc and iodine.

PMID- 21940306
TI  - Diagnosis of mesh infection after abdominal wall hernia surgery - role of
      radionuclide methods.
AB  - BACKGROUND/AIMS: The aim of this investigation was to evaluate the role of
      detection of late mesh infection following incisional hernia repair with
      radiolabeled antigranulocyte antibodies. METHODOLOGY: Mesh infection diagnoses
      were set up with clinical examination and laboratory analysis and confirmed by
      ultrasonography (US), computerized tomography (CT), scintigraphy with 99mTc
      antigranulocyte antibodies and microbiological examination. RESULTS: Of the 17
      patients investigated, 6 had a late mesh infection, and 11 had both mesh
      infection and recurrent incisional hernia. Clear clinical signs of late mesh
      infection were present in 13 patients. Four remaining patients had non-specific
      discomfort and recurrent incisional hernia without clinical manifestation of mesh
      infection ('silent infection'). US was positive in 12/17 patients, CT in 13/17
      patients, while scintigraphy with antigranulocyte antibodies in 17/17 patients.
      Therefore, sensitivity of US was 71%, of CT 76% and of scintigraphy 100%. In four
      patients late mesh infection was confirmed exclusively by 99mTc-antigranulocyte
      antibody scintigraphy, while US and CT did not indicate the infection.
      CONCLUSIONS: According to the present results, scintigraphy with 99mTc
      antigranulocyte antibodies is a useful method for the detection of 'silent'
      abdominal wall infections after surgery, which is very important for prompt and
      appropriate therapy.

PMID- 21940307
TI  - Rehabilitation exercise on the quality of life in anal sphincter-preserving
      surgery.
AB  - BACKGROUND/AIMS: In the recent years, there have been more and more patients with
      low rectal cancer who have received anal sphincter preserving surgery (ASPS). The
      defecation function greatly affects patient's postoperative social activity and
      quality of life. This study aimed to examine the effects of Kegel's exercise on
      postoperative anal defecation and quality of life of patients following sphincter
      preserving surgery. METHODOLOGY: A total of 34 patients received sphincter
      preserving surgery. 17 patients received instruction for Kegel's exercise
      postoperatively and 17 patients did not. Defecation function and quality of life
      were compared between the two groups by FACT-C questionnaire. RESULTS: The
      response rate of FACT-C questionnaire was 64.7% (22 in 34 patients). These 22
      patients were divided into two groups: exercise group (n=11) and the non-exercise
      group (n=11). No significant differences were found in the demographic data
      between the two groups. Although the defecation frequency of the exercise group
      was better than the non-exercise group, no statistical difference was found. The
      total scores of the quality of life of the exercise group were significantly
      higher than those in the non-exercise group (p=0.038). CONCLUSIONS: This
      preliminary study found that Kegel's exercises may have a positive impact on the
      quality of life in patients undergoing anal sphincter preserving surgery.

PMID- 21940308
TI  - A genetic association between beta3-aderenoceptor and cholinergic receptor
      muscarinic 3 polymorphisms in irritable bowel syndrome.
AB  - BACKGROUND/AIMS: We examined the association of beta3-adrenoceptor (beta3-AR) and
      cholinergic receptor muscarinic 3 (CHRM3) polymorphisms with irritable bowel
      syndrome (IBS). METHODOLOGY: DNA was obtained from 81 IBS patients (39 diarrhea
      type, IBS-D; 25 constipation type, IBS-C, 5 mixed type, IBS-M; and 12 unsubtyped,
      IBS-U) and 73 controls. For the analyses IBS-(M + U) was combined into one group
      (NonDNonC). beta3-AR and CHRM3 polymorphisms were determined by the polymerase
      chain reaction (PCR)-based restriction fragment length polymorphism (RFLP)
      method. RESULTS: The beta3-AR genotype frequencies of T/C in IBS patients were
      significantly higher compared to those in controls. The distribution of the CHRM3
      genotypes, C/C, T/C and T/T, was not significantly different between IBS patients
      and controls. The distribution of the beta3-AR and CHRM3 genotypes was not
      significantly different between IBS-D, IBS-C and NonDNonC. The frequencies of the
      CHRM3 genotypes in IBS were significantly different between disease duration
      greater than and less than 3 years. CONCLUSIONS: beta3-AR polymorphisms in IBS
      patients are different compared to controls, and CHRM3 polymorphisms are also
      likely associated with disease duration in IBS. beta3-AR and CHRM3 polymorphisms
      could be associated with IBS.

PMID- 21940309
TI  - Serial changes of cytokines in Crohn's disease treated with infliximab.
AB  - BACKGROUND/AIMS: Infliximab (IFX) has been reported to be useful as induction
      therapy and/or maintenance therapy for Crohn's disease (CD). However, the effects
      of IFX on serial changes in cytokine levels have not been well characterized. We
      examined cytokine levels in CD patients before and after administration of IFX.
      METHODOLOGY: A total of 37 patients with active CD were enrolled (24 men, 13
      women; mean age, 31.9 years). Patients were given IFX 5mg/kg intravenously. Serum
      levels of 17 cytokines were simultaneously determined using a Bio-Plex suspension
      array system before treatment and, 4 and 8 weeks after IFX treatment. Patients
      were divided into two groups according to the disease duration: the 'early
      treatment' group and the 'in progress' treatment group. RESULTS: Serum IL-6, IL
      7, IL-8 and MIP-1beta levels were significantly decreased in CD patients after
      IFX treatment compared to before treatment (p<0.05). In particular, serum levels
      of IL-8, IL-12 and MIP-1beta decreased significantly after IFX treatment in the
      'in progress' treatment group. The changes in CD activity score (CDAI) after
      treatment were positively correlated with the changes of serum MIP-1beta.
      CONCLUSIONS: IFX treatment reduces serum levels of IL-6, IL-7, IL-8, IL-12 and
      MIP-1beta, which appears to be mediated by the inhibition of inflammation in CD.

PMID- 21940311
TI  - Study of segmental colonic transit time in healthy men.
AB  - BACKGROUND/AIMS: There are few reports of the segmental colonic transit time
      (SCTT) in healthy men. To clarify the SCTT for healthy men, the author measured
      the SCTT of healty men using radiopaque markers (RM). METHODOLOGY: The author
      analyzed the SCTT of 26 healthy men, who were aged from 24 to 60 years and had a
      mean age of 48.8 years, with RM (20 radiopaque polyvinyl chloride 0-rings). The
      criteria for participation included a usual stool frequency of between three per
      week and three per day, no history of gastrointestinal disease, and no use of
      medications known to affect gastrointestinal motility. RESULTS: The overall
      gastrointestinal transit time was 36.2+/-5.1 hours, and the transit time from the
      mouth to the cecum was 6.8+/-1.4 hours. The half-dose transit times of the
      ileocecal valve, hepatic flexure, splenic flexure, descending-sigmoid line, and
      evacuation were 6.9+/-1.6, 15.9+/-1.7, 18.8+/-1.7, 24.3+/-4.4 and 36.4+/-5.3
      hours, respectively. The ascending (9.5+/-2.3 hours) and descending colon (5.5+/
      4.1 hours) had shorter transit times than the sigmoid-rectum section (12.7+/-2.1
      hours) (p<0.001, p<0.01, respectively), and the transverse colon (4.2+/-2.1
      hours) had a shorter transit time than the ascending colon (p<0.05). There were
      no significant differences in transit time between the descending and transverse
      colon. CONCLUSIONS: Measuring the SCTT using RM may be effective for detecting
      the SCTT of specific sections of the bowel. This method is simple and can be
      easily performed at any radiology department.

PMID- 21940312
TI  - Clinical experience and analysis of laparoscopic total mesorectal excision
      combined with improved Bacon for the treatment of lower rectal cancer.
AB  - This study is aimed at assessing the safety and feasibility of laparoscopic total
      mesorectal excision (LTME) combined with improved Bacon (IB) procedure in the
      treatment of lower rectal cancer. There were 347 patients undergoing sphincter
      preserving operation at the authors hospital from 2003 to 2009. Of these, there
      were 201 cases with double stapler technique (DST) anastomosis in high-location
      group (range 6 to 12cm); 76 cases with DST anastomosis in low-location subgroup A
      (range 5 to 6cm); and 70 cases with IB anastomosis in low-location subgroup B
      (range 5 to 6cm). In high-location group vs. low-location subgroup A, anastomotic
      leak rate and covering stoma rate in low-location subgroup A were obviously
      higher (p=0.038 and p=0.040); in low-location subgroup A vs. low-location
      subgroup B, operative time in low-location subgroup B was a little longer
      (p=0.000). However, anastomotic leak rate and covering stoma rate were
      significantly higher in low-location subgroup A (p=0.043 and p=0.043). DST can be
      applied as the first choice if the inferior margin of tumor to anal verge is 6 to
      12cm. For lower rectal cancer, 5 to 6cm from anal verge, when DST is not suitable
      for sphincter-preserving operation, IB anastomosis can be applied.

PMID- 21940310
TI  - Cyclopamine blocked the growth of colorectal cancer SW116 cells by modulating
      some target genes of Gli1 in vitro.
AB  - BACKGROUND/AIMS: Hedgehog (Hh) pathway has been considered as a therapy target
      for various cancer entities. However, its mechanism in colorectal cancer is still
      unclear. METHODOLOGY: We analyzed the expression of Hh pathway members in
      colorectal adenomas and cancer cell lines and then studied its relationship with
      survival of colorectal cancer cells through inhibiting Hh pathway by cyclopamine.
      Moreover, we studied the regulation of Gli1 on insulin-like growth factor binding
      protein 6 (IGFBP6) and B-cell CLL/lymphoma 2 (Bcl-2) genes at the level of
      transcription by XChIP and cyclopamine inhibition assay. RESULTS: Sonic hedgehog
      (Shh), Smoothened (Smo), patched (Ptch) and Gli1 genes mRNA were expressed in
      SW116 cells. Gli1 bound to promoter regions of Bcl-2 and IGFBP6 genes,
      cyclopamine inhibited proliferation and induced apoptosis through inhibiting the
      transcriptions of IGFBP6 (p=0.003), proliferating cell nuclear antigen (PCNA)
      (p=0.014) and Bcl-2 (p=0.013), and increasing that of BCL2-associated X protein
      (Bax) and BCL2-antagonist/killer 1 (Bak1) (p=0.003 and 0.001, respectively) in
      SW116 cells. CONCLUSIONS: Hh pathway is aberrant activation in part colorectal
      carcinomas cell lines and its inhibitor may be an effectual agent for colorectal
      cancer chemoprevention. It may be one of the mechanisms that Gli1 maintained cell
      survival by binding the promoter regions and facilitating transcription of IGFBP6
      and Bcl-2 genes.

PMID- 21940313
TI  - Serial changes in cytokine expression in irritable bowel syndrome patients
      following treatment with calcium polycarbophil.
AB  - BACKGROUND/AIMS: Calcium polycarbophil improves abdominal symptoms in patients
      with irritable bowel syndrome (IBS). We examined cytokine expression in IBS
      patients before and after administration of calcium polycarbophil. METHODOLOGY: A
      total of 24 IBS patients (13 diarrhea type, 11 constipation type; median age, 55
      years) were enrolled. Serum levels of high sensitive C-reactive protein (CRP) and
      17 cytokines (interleukin [IL]-1beta, -2, -4, 5, -6, -7, -8, -10, -12, -13 and 
      17; tumor necrosis factor-a [TNF-a]; interferon [IFN]-?; granulocyte colony
      stimulating factor [G-CSF]; granulocyte macrophage colony-stimulating factor [GM
      CSF]; macrophage inflammatory protein [MIP]-1beta; and macrophage chemo
      attractant protein [MCP-1]) were simultaneously determined using a Bio-Plex
      suspension array system before and 12 weeks after administration of calcium
      polycarbophil 1,500-3,000mg/day. RESULTS: Serum MCP-1 levels in diarrhea type IBS
      patients were significantly higher than those in constipation type patients
      (p<0.05). In IBS patients, no significant changes in serum cytokine levels were
      observed following calcium polycarbophil administration. In constipation type
      patients, serum high sensitive CRP levels were significantly lower after
      treatment than before treatment. CONCLUSIONS: Decreases in serum high sensitive
      CRP levels following calcium polycarbophil treatment may be involved in the
      relief of abdominal symptoms in IBS patients; diarrhea type IBS is characterized
      by increased MCP-1 expression.

PMID- 21940314
TI  - The efficacy of chemotherapy in patients with high-grade metastatic colon cancer.
AB  - BACKGROUND/AIMS: This study was undertaken to assess the prognostic role of
      histological grade in colon cancer and the efficacy of either oxaliplatin or
      irinotecan after incorporation into an infusional regimen of 5-fluorouracil and
      leucovorin in patients with high-grade metastatic colon cancer. METHODOLOGY: Data
      from 2409 consecutive and eligible patients with colon cancer from a single
      institute was used to assess the impact of histological grade on survival and the
      efficacy of the two doublet regimens on patients with metastatic colon cancer
      relative to histological grade. RESULTS: High histological grade has unfavorable
      outcome for patients with stage III (p=0.021) or stage IV (p=0.003) colon cancer
      but not for those with stage I (p=0.703) or stage II (p=0.767) colon cancer.
      Progression free survival and overall survival in patients with high-grade
      metastatic colon cancer were not improved by the addition of irinotecan or
      oxaliplatin to the infusional 5-fluorouracil + leucovorin regimen. CONCLUSIONS:
      Histological grade is a prognostic factor in stage III/IV colon cancer but not in
      stage I/II. Oxaliplatin and irinotecan may not enhance the efficacy of infusional
      5-fluorouracil + leucovorin in the treatment of high-grade metastatic colon
      cancer.

PMID- 21940315
TI  - Virtual ileostomy following rectal cancer surgery: a good tool to avoid unusefull
      stomas?
AB  - BACKGROUND/AIMS: Anastomotic leak is a life threatening complication following
      surgery for rectal cancer below peritoneal reflection. Colostomy or ileostomy
      following colorectal or coloanal anastomosis protect the patients from general
      peritonitis or sepsis secondary to anastomotic leak. METHODOLOGY: In this paper
      the experience of the last 100 cases of rectal cancer below the peritoneal
      reflection treated from 2004 to 2010 was reviewed. RESULTS: In 79 cases, primary
      anastomosis was performed. In 44/79 cases virtual ileostomy was prepared and in
      35/79 cases, based on risk factors and intraoperative decision of the surgeon, an
      open ileostomy was performed. In 8/44 cases virtual ileostomy was opened, thus
      avoiding in 35/79 cases a second operation. CONCLUSIONS: The goal for a good
      clinical outcome of patients with virtual ileostomy is a strict postoperative
      follow-up focused on fever onset and quality of drainage discharge. In our
      experience virtual ileostomy is a good tool to avoid open ostomy at time of
      primary colorectal or coloanal anastomosis in a good number of cases.

PMID- 21940316
TI  - Laparoscopic total mesorectal excision for rectal cancer after neoadjuvant
      treatment: targeting sphincter-preserving surgery.
AB  - BACKGROUND/AIMS: Laparoscopic total mesorectal excision for rectal cancer is
      under scrutiny. This study aimed at analyzing feasibility, adequacy of resection,
      impact on early outcomes after neoadjuvant chemoradiation therapy, and to
      investigate trend towards indication of laparoscopy for sphincter-preservation in
      a single university medical center. METHODOLOGY: Patients with distal rectal
      cancer submitted to neoadjuvant treatment followed by laparoscopic total
      mesorectal excision were prospectively enrolled. The studied parameters were:
      demographics, previous surgery, BMI, type of operation, rate of sphincter
      preserving surgery, duration of surgery, conversion, specimen retrieval,
      lymphadenectomy, distal and radial margins, intra and postoperative morbidity,
      reoperations, hospital stay, and mortality. RESULTS: From January 2000 to July
      2010, 68 patients were enrolled. Mean age was 60 (30-87) years. There were 27
      anterior and 41 abdominoperineal resections. Six patients underwent a totally
      laparoscopic resection and coloanal anastomosis. There was a trend (p=0.003)
      towards more sphincter-preserving surgery. Conversion was 4.5%. Intraoperative
      complication was 7.4%. Postoperative complications occurred in 15%. Mortality was
      3%. Lymph-node harvest was 11 (0-33). Mean distal margin was 2.5cm (1-4). Radial
      margins were positive in 3 (10%) cases. CONCLUSIONS: Laparoscopic total
      mesorectal excision after neoadjuvant treatment is feasible and safe. Sphincter
      preserving laparoscopic oncologic rectal surgery has been accomplished more
      frequently.

PMID- 21940317
TI  - The prognostic role of apoptosis mediators in rectal adenocarcinoma.
AB  - BACKGROUND/AIMS: Genes included in apoptosis may be involved in tumor biology and
      identify specific groups of patients with individual therapy. The aim of this
      study was to evaluate the prognostic value of some apoptosis markers in
      conjunction with pathological factors in operable rectal cancer patients.
      METHODOLOGY: Tumor samples from 87 patients with rectal adenocarcinoma were
      analyzed retrospectively. The immunohistochemistry from 'tissue array' for the
      expression of p53, p21, Bcl-2 and cycline D1, combined with pathological features
      were correlated with the survival data. The mean postoperative follow-up was 48
      months. RESULTS: Five-year cancer-specific survival (CSS) was 44.9%. Independent
      prognostic factors for CSS were the p53 and p21 proteins, whereas for cancer-free
      survival (CFS) p21 was a positive independent factor. When pathological factors
      were also introduced in the analysis, the positive prognostic role on CSS was
      obtained for p21 and lymphatic invasion; CFS was positively influenced by the
      presence of p21 protein and lymphatic invasion. For patients with pN0, p21
      protein was an independent predictive marker for CSS and CFS. CONCLUSIONS:
      Molecular markers of apoptosis, such as p53 and p21, had significant prognostic
      role in rectal cancer patients, together with lymphatic invasion. The presence of
      p21 protein in pN0 patient outcome may influence management, but needs further
      evaluation.

PMID- 21940318
TI  - Serum fibrinogen level predicts the therapeutic response and prognosis in
      patients with locally advanced rectal cancer.
AB  - BACKGROUND/AIMS: Preoperative chemoradiotherapy has become the current gold
      standard treatment for locally advanced rectal cancer. To date, no suitable
      prognostic markers could be used to identify rectal cancer patients who are most
      likely to experience a good outcome after preoperative chemoradiotherapy. The
      goal of this study was to evaluate whether serum fibrinogen level is suitable as
      a predictor of therapeutic response to preoperative chemoradiotherapy and
      prognosis for locally advanced rectal cancer. METHODOLOGY: The study
      retrospectively analyzed the correlation between the pretherapeutic fibrinogen
      level and cancer response as well as prognosis in 53 patients with locally
      advanced rectal cancer who underwent preoperative chemoradiotherapy followed by
      surgery. Serum fibrinogen level more than 4.00g/L was defined as
      hyperfibrinogenemia. RESULTS: Of the 53 patients, thirty-four (64.2%) had a
      fibrinogen level less than or equal to 4g/L (hypofibrinogenemia) and the other 19
      cases above 4g/L (hyperfibrinogenemia). Ten of the studied 53 patients (18.9%)
      had a pathologic complete response after preoperative chemoradiotherapy. The
      percentage of patients who experienced a pathological complete response was lower
      among patients with hyperfibrinogenemia than those with hypofibrinogenemia (5.3%
      vs. 26.5%). Concerning the survival, 68.4% (13/19) patients with
      hyperfibrinogenemia died of disease, while only 29.4% (10/34) in
      hypofibrinogenemia group. The Kaplan-Meier survival curves of patients with
      hypofibrinogenemia versus hyperfibrinogenemia showed a highly significant
      separation (p<0.05). CONCLUSIONS: For locally advanced rectal cancer patients,
      pre-therapeutic fibrinogen level might be a useful predictor of prognosis, and it
      might also be used as a biomarker to predict the therapeutic response.

PMID- 21940319
TI  - Acetazolamide inhibits aquaporin-1 expression and colon cancer xenograft tumor
      growth.
AB  - BACKGROUND/AIMS: To study the effects of water channel protein inhibitor
      acetazolamide on xenograft tumor growth of colon cancer in nude mice.
      METHODOLOGY: Setting up human colon cancer model in nude mice, mice were randomly
      divided into two groups as experimental group and control group. Acetazolamide
      was given at a volume of 0.1mL per mice (40mg/kg/d, ig) in experimental group,
      while the same volume of sterile saline was given in control group (ig). After 21
      days, protein and m-RNA levels of AQP-1 in tumor tissues from two groups were
      detected respectively by Western blot and RT-PCR to evaluate the treatment
      effects. AQP-1, VEGF and CD34 expression was detected by immunohistochemistry,
      simultaneously. RESULTS: Acetazolamide (40mg/kg/d, ig) significantly inhibited
      the xenograft tumor growth of colon cancer in nude mice. The inhibition rate was
      88.28%. In comparison with the control group, AQP-1 protein and mRNA level were
      significantly reduced in the experimental group (p<0.01). AQP-1, VEGF and CD34
      expression in experimental group were positively correlated between each other
      (p<0.01). CONCLUSIONS: Acetazolamide can suppress the xenograft tumor growth by
      inhibiting the expression of AQP-1.

PMID- 21940320
TI  - Oncolytic herpes virus induces effective anti-cancer immunity against murine
      colon cancer.
AB  - BACK GROUND/AIMS: Oncolytic virus therapy is becoming a promising anti-cancer
      therapy and oncolytic viruses have been shown to elicit anti-cancer immunity. We
      evaluated the anti-tumor immune responses elicited by the herpes oncolytic virus
      R3616 compared to a representative chemotherapy drug, 5-FU. METHODOLOGY: R3616 or
      5-FU was directly injected into subcutaneous tumors of non-immunized mice.
      Additionally, complete adjuvant, R3616-infected MC26 cells or 5-FU plus MC26
      cells were frozen, thawed and used to immunize mice. After 21 days of
      immunization, the adaptive immune response suppressed implanted tumor growth and
      prolonged survival rate. We monitored differences in the number of infiltrating
      CD8- and CD4-positive lymphocytes in implanted tumors by immunofluorescence.
      RESULTS: R3616 induced a statistically greater number of infiltrating T cells
      (Thy1.2), macrophages (CD68) and dendritic cells (CD83) in injected tumors than 5
      FU. The group immunized with R3616-infected MC26 cells had greater tumor
      suppression and longer survival rate than non-immunized mice and mice treated
      with 5-FU plus MC26 cells with statistically significant differences between
      these groups. The mice immunized with R3616-infected MC26 cells had a
      statistically greater number of infiltrating T cells in the implanted tumor than
      non-immunized and mice treated with 5-FU plus MC26 cells. CONCLUSIONS: These
      results indicate that oncolytic herpes virus R3616 can elicit more effective host
      anti-tumor immune responses than 5-FU against murine colon cancer model.

PMID- 21940321
TI  - Successful endosocpic submucosal dissection for esophageal squamous cell
      carcinoma together with a lipoma.
AB  - Superficial carcinomas over submucosal tumors of the esophagus have seldom been
      detected. Esophageal lipomas are very rare and only a few cases have been
      reported. We describe the case of a 73-year-old man with superficial squamous
      cell carcinoma overlying a lipoma. We successfully performed en bloc resection by
      endoscopic submucosal dissection (ESD) using the IT-knife. Histological
      examination showed curative resections. In such cases, ESD may be a promising
      tool to perform less invasive treatment.

PMID- 21940322
TI  - Effect of proton pump inhibitor (PPI) treatment in obstructive sleep apnea
      syndrome: an esophageal impedance-pHmetry study.
AB  - BACKGROUND/AIMS: There is an increasing interest for a link between
      gastroesophageal reflux (GER) and obstructive sleep apnea syndrome (OSAS). There
      is no study in the literature which examines the relationship between OSAS and
      esophageal functions in adults with impedance. We first evaluated the role of
      reflux in OSAS with simultaneous polysomnography and impedance-pHmetry and then
      investigated whether the effect of proton pump inhibitor (PPI) treatment changes
      in these parameters. METHODOLOGY: Twenty two OSAS patients who had applied to
      sleep laboratory between September 2007 and May 2008 were consecutively enrolled
      to the study. Twenty four hours esophageal impedance study was performed during
      polysomnographic recording. At least 50% of all apneas in patients must proceed
      with a reflux event in 2 minute intervals in order to be considered reflux
      related apnea patient. RESULTS: Pathologic reflux episodes were determined in 20
      patients (8 were weakly acidic, 12 were acidic). Reflux dependent apnea was found
      in 6 patients. There was endoscopically esophagitis in all reflux related apnea
      patients. There was a negative correlation between initial mean SaO2 and gas
      reflux events at night (p=0.004, r =-0.588) and mixed reflux events at night
      (p=0.02, r=0.493). There was a statistically significant regression of AHI (apnea
      hypopnea index) after 3-months PPI treatment (p=0.012). CONCLUSIONS: Reflux may
      trigger apnea in some of the OSAS patients. Therefore, each OSAS patient must be
      inquired about esophageal and extraesophageal symptoms of reflux.

PMID- 21940323
TI  - Effect of PPI (rabeprazole) on reflux esophagitis after total gastrectomy.
AB  - BACKGROUND/AIMS: Esophagitis after total gastrectomy has been associated with
      biliary and pancreatic reflux into the esophagus. The aim is to clarify the
      effect of PPI (rabeparazole) on these factors in esophagitis. METHODOLOGY:
      Sixteen 8-week old male Wistar rats underwent total gastrectomy and
      esophagoduodenostomy to induce esophageal reflux of duodenal juice. In 5 rats,
      the sham operation induced a midline laparotomy alone. One week following
      surgery, they were treated with control (saline) or PPI (rabeprazole) (30mg/kg)
      ip. Three weeks after operation, all rats were euthanized and the esophagus was
      evaluated histologically. Esophageal injury was evaluated by macroscopic and
      microscopic findings, and expression of COX2 and PGE2. Esophageal washing was
      aspirated for the evaluation of bile acid activity. RESULTS: At 3 weeks after
      surgery, duodenal reflux induced esophageal erosions and ulcer formation as well
      as marked thickening of esophageal wall. The macroscopic ulcer score and
      histological ulcer length were significantly reduced by treatment with
      rabeprazole. The enhanced expression of COX2 and PGE2 in the control group was
      also markedly inhibited in the rabeprazole treated group. The bile acid activity
      in the esophageal lumen was significantly increased in the control group and this
      increase was significantly inhibited in the rabeprazole treated group.
      CONCLUSIONS: Rabeprazole significantly reduces inflammation and hyperplasia in
      esophageal mucosa. These results indicate that bile acid, inhibited by
      rabeprazole, plays an important role in mucosal damage induced by duodenal
      reflux.

PMID- 21940324
TI  - Effects of proton pump inhibitors in patients with laryngopharyngeal reflux
      disease.
AB  - BACKGROUND/AIMS: The effect of proton pump inhibitors (PPIs) on the health
      related quality of life (HRQoL) of patients with laryngopharyngeal reflux disease
      (LPRD) is not well known. Our aim was to assess the HRQoL before and after
      administration of a PPI in patients with LPRD. METHODOLOGY: A total of 27 LPRD
      patients (14 women, 13 men; mean age 54 years) were enrolled. We determined the
      HRQoL using three different inquiry systems: 1) Frequency Scale for the Symptoms
      of GERD (FSSG); 2) the 36 item short form of the Medical Outcome Study
      Questionnaire (SF-36); and 3) the Gastrointestinal Symptom Rating Scale (GSRS).
      The HRQoL was determined at baseline and after eight weeks of treatment with
      lansoprazole at a dose of 30mg once daily or rabeprazole at a dose of 10mg once
      daily. RESULTS: After administration of the PPI, the FSSG, the SF-36 general
      health scale and mental health scale, GSRS reflux syndrome score, abdominal pain
      syndrome score and the indigestion syndrome score were significantly improved
      compared to baseline pretreatment scores (p<0.05). CONCLUSIONS: PPI therapy would
      be useful for the treatment of LPRD.

PMID- 21940325
TI  - Diagnosis of hepatic hemangioma by parametric imaging using sonazoid-enhanced US.
AB  - BACKGROUND/AIMS: Comparison of Parametric Imaging (PI) using Sonazoid-enhanced
      ultrasonography (US) and microflow imaging (MFI) to determine the possibility of
      hepatic hemangioma diagnosis using PI. METHODOLOGY: Twenty-two hepatic hemangioma
      nodules (mean+/-SD diameter: 31.6+/-19.1mm) undergoing Sonazoid-enhanced US
      between February 2008 and March 2009. After Sonazoid-enhanced US, COMMUNE
      ultrasonographic image analysis software was used for analysis of tumor imaging
      dynamics in the vascular phase using PI and MFI. In PI, 0s was set as the time
      contrast agent reached the tumor. Imaging within the tumor after 0s was color
      coded according to time, and the images were displayed in color. In MFI, 0s was
      set as the time contrast agent reached the tumor. The path of microbubbles as it
      flowed through blood vessels was superimposed on the original B-mode images.
      Three trained physicians used these methods to analyze tumor imaging dynamics.
      RESULTS: All physicians concluded all cases were hepatic hemangioma regardless of
      method used. However, compared to MFI, PI allowed determination of more detailed
      blood flow dynamics in high-flow hepatic hemangioma, where blood flow speed was
      faster than in normal hepatic hemangioma. CONCLUSIONS: It is possible to diagnose
      hepatic hemangioma using PI using sonazoid-enhanced US.

PMID- 21940326
TI  - Transition of serum alkaline phosphatase isoenzymes during liver regeneration in
      humans.
AB  - BACKGROUND/AIMS: Serum alkaline phosphatase (ALP) levels tend to increase after
      hepatectomy. However, no previous examinations have yet focused on the
      relationship between liver regeneration and the individual ALP isoenzymes levels.
      METHODOLOGY: Forty living liver transplantation donors who underwent hemi
      hepatectomy were herein investigated. We evaluated the serum ALP levels and ALP
      isoenzyme levels preoperatively and postoperatively. The liver regeneration rate
      (LRR) was calculated using volumetry. According to the LRR, we divided the donors
      into two groups, consisting of a high regeneration group (HG) and a low
      regeneration group (LG). RESULTS: The total serum ALP levels increased gradually
      after hepatectomy and peaked on postoperative day (POD) 14. ALP-1 was not
      detected in any donor preoperatively. However, it was detected after hepatectomy,
      peaking on POD 7. The serum ALP-2 level increased after hepatectomy, reaching a
      peak level on POD 14. The ALP-2 levels gradually increased after hepatectomy and
      reached peak levels on POD 14 in both groups. However, the ALP-2 level on POD 14
      was significantly higher in HG than LG. CONCLUSIONS: The serum ALP-2 levels after
      POD 14 might therefore be a useful indicator of favorable liver regeneration
      following hepatectomy, especially in patients who have a normal liver function.

PMID- 21940327
TI  - Hypoxia inducible factor expression in intrahepatic cholangiocarcinoma.
AB  - BACKGROUND/AIMS: Intrahepatic cholangiocarcinoma (IHCC) is known to be one of the
      most malignant tumors. Hypoxia-inducible factor-1 (HIF-1) is a transcription
      factor, which plays a central role in biologic processes under hypoxic
      conditions. The aim of this study was to elucidate the role of HIF-1 in IHCC.
      METHODOLOGY: Thirty-five patients with IHCC who underwent hepatic resection were
      enrolled in this study. The expression of HIF-1a was determined
      immunohistochemically and the patients were divided into two groups: HIF-1a
      positive group (n=22) and HIF-1a negative group (n=13). Clinicopathological
      variables including prognosis were compared between the two groups. The
      prognostic factors were investigated by multivariate analysis using Cox's
      proportional hazard model. RESULTS: HIF-1a expression correlated significantly
      with higher stage, and tended to correlate with tumor diameter (>4cm), vessels
      infiltration and intrahepatic metastasis. The prognosis in HIF-1a positive group
      was poorer than that in HIF-1a negative group (5-year survival: 62.9% vs. 18.3%).
      Furthermore, HIF-1a positive expression was identified as an independent
      prognostic factor for both overall and disease free survival. CONCLUSIONS: The
      findings suggested that the intratumoral HIF-1a regulated malignant behavior and
      was a new prognostic indicator of IHCC.

PMID- 21940328
TI  - Laparoscopic floppy Nissen fundoplication: 16 years of experience from the
      historical clinic of Rudolph Nissen.
AB  - BACKGROUND/AIMS: Since its original description in 1956 by Rudolph Nissen, minor
      changes were made in technical details of Nissen fundoplication. After the
      introduction of laparoscopic fundoplication, in order to reduce the rate of
      complications, some technical modifications led to the development of 'floppy'
      Nissen fundoplication. METHODOLOGY: From August 1993 to August 2009, laparoscopic
      Nissen fundoplication was performed on 2100 patients, 17 of whom underwent
      classical and 2083 underwent floppy fundoplication. All the operations were
      performed by the same surgical team. Preoperative work-up included 24-h pH
      monitoring, esophagogastroduodenoscopy and barium cineradiography. Esophageal
      manometry was not performed due to the physical impossibility of this tool at our
      clinic. Key steps of the operation were dissection of the hepatogastric and
      Laimer's ligament, dissection and closure of the hiatus, and short, floppy Nissen
      fundoplication. Phrenoesophageal ligament was divided to obtain at least of 4cm
      of an abdominal esophagus. RESULTS: On the follow-up, dysphagia lasted for 1
      month in 5.2% (110), between 1-3 months in 0.7% (16) and more than 3 months in
      0.1% (3) of patients. Mortality was seen in 1 (0.05%) patient, and it was related
      to fatal pulmonary vein injury during perioperative bougienage. CONCLUSIONS:
      Laparoscopic floppy Nissen fundoplication seems to be a safe and feasible
      technique for surgical treatment of gastroesophageal reflux disease.

PMID- 21940329
TI  - A breakdown of the Hippo pathway in gastric cancer.
AB  - BACKGROUND/AIMS: The Hippo pathway is a newly discovered signaling pathway. In
      mammals, the Hippo pathway was reported to be a tumor-suppressor signaling that
      inhibited cell proliferation and promoted cell apoptosis. Inactivation of the
      Hippo pathway resulted in massive cell growth, enlargement in organ size and
      eventually cancer formation. The aim of this study was to investigate the
      expression of core component proteins of the Hippo pathway, Mst1/2,S Sav1 and
      Lats1, in normal gastric mucosa, intestinal metaplasia and gastric cancer, and to
      explore the role of the Hippo pathway in gastric cancer. METHODOLOGY: Two-step
      immunohistochemical staining was used to detect the expression of Mst1/2, Sav1
      and Lats1 in 46 cases of normal gastric mucosa, 37 cases of intestinal metaplasia
      and 78 cases of gastric cancer. RESULTS: The expression of Mst1/2 and Lats1 was
      down-regulated in gastric cancer compared with that in normal gastric epithelium
      and adenoma. The Sav1 expression showed an increased trend from normal mucosa
      through intestinal metaplasia to gastric cancer, though there was no
      statistically significant difference. The expression of Sav1 and Lats1 in gastric
      cancer with lymph node metastasis was significantly lower than that without lymph
      node metastasis. CONCLUSIONS: A breakdown of the Hippo pathway may play a role in
      tumorigenesis and metastasis of gastric cancer.

PMID- 21940330
TI  - Surgical modalities for gastric carcinoma with concurrent portal hypertension: a
      retrospective study.
AB  - BACKGROUND/AIMS: Abdominal surgery in gastric carcinoma patients with concurrent
      portal hypertension (PHT) is highly risky due to liver function impairment. This
      study aimed to identify the optimal surgical modalities for the concomitant
      conditions METHODOLOGY: Thirty patients with gastric adenocarcinoma and
      concurrent PHT who received radical (n=28) or palliative (n=2) gastrectomy plus
      D0/D1 (n=12) or D2 (n=18) lymphadenectomy, were reviewed. Logistic and Cox
      regression analysis were used to determine the correlation of predefined
      perioperative factors with surgical morbidity and overall survival (OS),
      respectively. RESULTS: Sixteen (53.3%) patients experienced postoperative
      complications; the rates were 26.7% (4/15), 72.7% (8/11) and 100.0% (4/4) in
      patients with Child-Pugh classification (CPC) Class A, B and C, respectively.
      Five (16.7%) patients did not survive due to pulmonary embolism (n=1),
      anastomotic leakage (n=2), and multiple organ dysfunction syndrome (n=2). The
      median survival time was 15.0 months. TNM staging (p=0.027), CPC (p=0.048) and
      preoperative ascites (p=0.001) were significantly associated with OS as
      determined in the multivariate analysis. CONCLUSIONS: Concomitant surgical
      treatment of PHT depends on the presence of hypersplenism and variceal bleeding
      risk. Baseline CPC, tumor TNM staging and the preoperative ascites predict the
      risks of surgical complications and long-term outcome.

PMID- 21940331
TI  - Intramuscular injection of metoclopramide decreases the gastric transit time and
      does not increase the complete examination rate of capsule endoscopy: a
      prospective randomized controlled trial.
AB  - BACKGROUND/AIMS: Capsule endoscopy (CE) reaches the cecum in about 80% of cases.
      Decreasing the gastric transit time (GTT) may increase the complete examination
      rate (CER). METHODOLOGY: Patients (n=177) were prospectively randomized into 2
      groups: the control group (n=88) and the intramuscular injection with
      metoclopramide (IIM) group (n=89). The OMOM CE system, which has the function of
      real-time monitoring, was used. The patients were injected with metoclopramide 15
      minutes before swallowing the CE in the IIM group. The CE would be sent into the
      duodenum by gastroscopy if the GTT reached 120 minutes in the two groups.
      RESULTS: No significant difference was noted between the two groups. Of the 169
      cases without gastroscopic help, the mean GTT was shorter in the IIM group (n=87)
      than the control group (n=82) (p=0.002). But the CER was similar. Of 135 cases
      without gastroscopic help but reached the cecum, the mean GTT was shorter in the
      IIM group (n=71) than the control group (n=64) (p=0.015). But the mean small
      bowel transit time (SBTT) was similar. CONCLUSIONS: Intramuscular injection of
      metoclopramide decreases the gastric transit time, but it does not change the
      SBTT or CER of capsule endoscopy in our study.

PMID- 21940332
TI  - Accuracy of pulse oximetry in the detection of hypoxia in liver transplant
      candidates.
AB  - BACKGROUND/AIMS: Hypoxia is common in patients with chronic liver disease.
      Screening guidelines for detecting the presence of arterial hypoxemia do not
      exist. The aim of this study was to investigate the accuracy and utility of pulse
      oxymetry in the detection of hypoxemia (PaO2<65) in a group of patients with
      liver cirrhosis who were candidate for liver transplantation. METHODOLOGY: Two
      hundred and ninety-five transplant candidates enrolled in this study. Arterial
      oxyhemoglobin saturation was obtained by pulse oxymetry (SpO2) and compared with
      simultaneous arterial blood gas (ABG) oxyhemoglobin values (SaO2). Bias, the
      overestimation or underestimation of one method compared with another, is defined
      as the difference between SpO2 and SaO2. RESULTS: SpO2 overestimated SaO2 in
      78.3% (n=231) and underestimated in 18.6% (n=54) cases. The bias was over 4% or
      less than -4% (Bias4) in 11.6% (n=34) of the cases and significantly different
      between the patients with SaO2 =94%. PaO2 =65 mmHg (p=0.000) and SpO2 =94%
      (p=0.003). Also, when we used the cut-off level of A-a O2 gradient =20 and =15,
      the bias was significantly different between the patients (p=0.000). CONCLUSIONS:
      Pulse oximetry is a useful screening test to detect hypoxemia in patients with
      liver disease.

PMID- 21940333
TI  - Effects of ANGPTL3 antisense oligodeoxynucleotides transfection on the cell
      growths and invasion of human hepatocellular carcinoma cells.
AB  - BACKGROUND/AIMS: The aim of this study was to investigate the effects of
      antisense oligodeoxynucleotides transfection of angiopioetin-like protein 3
      (ANGPTL3) on the proliferation and invasion capacities of human hepatocellular
      carcinoma SMMC-7721 cells in vitro. METHODOLOGY: ANGPTL3 antisense
      oligodeoxynucleotides was transfected into SMMC-7721 cells with Lipofectamine
      2000. We used MTT assay to evaluate cell growth. ANGPTL3, p38 mitogen-activated
      protein kinases (MAPKs) and Matrix metalloproteinase-9 (MMP-9) mRNA expression
      levels were evaluated by RT-PCR. The invasive potency of SMMC-7721 cells was
      measured by the transwell cell invasion assay. RESULTS: ANGPTL3 antisense
      oligodeoxynucleotides were successfully transfected into SMMC-7721 cells,
      resulting in the significant inhibition of ANGPTL3, p38MAPK and MMP-9 mRNA
      expression. Downregulation of ANGPTL3 inhibited cell proliferation and decreased
      invasion of SMMC-7721 cells. CONCLUSIONS: ANGPTL3 may be functionally involved in
      hepatocellular carcinoma cell proliferation and invasion and is a potential
      target for hepatocellular carcinoma therapy.

PMID- 21940334
TI  - Treatment outcomes of surgical resection for hepatocellular carcinoma with
      inferior vena cava invasion and/or thrombosis.
AB  - BACKGROUND/AIMS: Advanced hepatocellular carcinoma with either an invasion of the
      inferior vena cava or thrombosis is rare, and its prognosis is extremely poor.
      There is no established treatment. The purpose of this study was to evaluate the
      efficacy of surgical resection and its prognosis in 5 recent cases. METHODOLOGY:
      From January 2005 to December 2008, 5 patients diagnosed with advanced
      hepatocellular carcinoma with inferior vena cava invasion and/or thrombosis
      underwent surgical resection. These patients were retrospectively reviewed.
      RESULTS: The mean age at diagnosis was 54 years. There were 4 men and 1 woman.
      According to the Child-Pugh classification, all patients were class A. One case
      had 2 hepatic masses, and the others had a solitary hepatic mass. The mean tumor
      size was 5.53cm. All 5 patients underwent partial hepatectomy and inferior vena
      cava resection or thrombosis removal. Among these, 4 cases needed a
      cardiopulmonary bypass. Four patients survived and 1 patient expired at the point
      of analyzing. Four cases experienced recurrences. The mean disease-free survival
      time was 19.6 months. One patient has been followed-up for 43 months without any
      recurrences up to now. CONCLUSIONS: Concurrent en-bloc resection of the liver and
      inferior vena cava for progressive HCC accompanying IVC invasion or thrombosis
      can be considered as a curative treatment.

PMID- 21940335
TI  - Preoperative levels of serum interleukin-6 in patients with hepatocellular
      carcinoma.
AB  - BACKGROUND/AIMS: A high prevalence of serum IL-6 has been associated with the
      pathogenesis of hepatocellular carcinoma (HCC) in both animals and humans.
      However, it is not clear how the levels of serum IL-6 influence the prognosis of
      HCC patients. This study was carried out in order to attempt to answer this
      question. METHODOLOGY: A total of 156 adults were selected and categorized into
      four groups: healthy subjects (n=18), those with tumor recurrence (n=26), those
      initially diagnosed with HCC (n=32), and those with HCC (n=80) who received
      curative resection between 2002 and 2004 with five years of follow-up. Serum IL-6
      levels were determined in all subjects by the same ELISA method. RESULTS: IL-6
      was found in high levels in the serum of patients initially diagnosed with HCC
      (8.47+/-5.92, p<0.0001) and in patients with HCC and tumor recurrence (12+/
      31.90, p=0.001) compared with healthy subjects (0.89+/-1.51). This includes all
      patients who received therapy between 2007 and 2008. The levels of serum IL-6
      were positively correlated with tumor size (p=0.002) in the HCC patients who
      received curative resection between 2002 and 2004 with five years of follow-up.
      CONCLUSIONS: High levels of serum IL-6 correlated positively with tumor size and
      with poor prognosis in HCC patients.

PMID- 21940336
TI  - Reduced glutathione protects human hepatocytes from palmitate-mediated injury by
      suppressing endoplasmic reticulum stress response.
AB  - BACKGROUND/AIMS: The aim of this study was to investigate the protective role of
      reduced glutathione (GSH) in hepatocytes by suppressing palmitate-induced
      endoplasmic reticulum (ER) stress. METHODOLOGY: Human L02 hepatocytes were co
      cultured with palmitate and reduced GSH. Cell viability and apoptosis were
      measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide
      (MTT) assay and Annexin V/ PI (propidium iodide) staining with flow cytometry,
      respectively. Lipid peroxidation was assessed by malonaldehyde (MDA) and oxidized
      glutathione (GSSG) measurements. Levels of ER stress signaling proteins
      (phosphorylated PRK-like ER kinase, activating transcription factor 4 and glucose
      regulating protein 78) as well as Caspase-4 activity were also analyzed. RESULTS:
      Palmitate caused an increased lipid peroxidation level and cytotoxic effect in
      hepatocytes in a concentration-dependent and time-dependent manner. However, a
      significant cell protective effect was observed after GSH treatment. The protein
      levels of GRP78, pPERK and AFT4 as well as the mRNA level of ATF4 were
      significantly increased after palmitate treatment, and these levels decreased
      after GSH addition. Additionally, Caspase-4 activity significantly increased
      after palmitate addition and strongly decreased after the addition of GSH.
      CONCLUSIONS: ER stress provoked by lipid peroxidation is a key event that
      mediates palmitate cytotoxicity in hepatocytes. Reduced GSH has a protective
      effect by suppressing palmitate-induced ER stress.

PMID- 21940337
TI  - Impaired activation of phosphatidylinositol 3-kinase by leptin is a novel
      mechanism of hepatic leptin resistance in NAFLD.
AB  - BACKGROUND/AIMS: The aim of this study was to detect the levels of leptin in
      serum and the expression of leptin, obesity receptor (OB-R), phosphatidylinositol
      3-Kinase (p85) (PI3-K p85) and phospho-Akt-kinase (Akt) in non-alcoholic fatty
      liver disease (NAFLD). METHODOLOGY: The expressions of leptin, OB-R and PI3-K/
      Akt kinase pathway were examined by immunohistochemistry. The level of leptin in
      serum was measured by radioimmunoassay. RESULTS: In agreement with significantly
      elevated serum leptin levels in NAFLD patients (p<0.05), expression of leptin, OB
      R and PI3-K (p85) was significant higher in NAFLD patients (p<0.05) compared with
      the control patients. In contrast, expression of Akt was significantly down
      regulated in the NAFLD patients (p<0.05). Moreover, PI3-K (p85) expression was
      significantly, positively correlated with leptin (r= 0.365, p<0.05) but
      negatively correlated with Akt (r=-0.854, p<0.01). CONCLUSIONS: Leptin may be
      involved in NAFLD pathogenesis by activating the PI3-K/Akt kinase pathway via OB
      R and the defective leptin activation of PI3-K is a novel mechanism of leptin
      resistance in NAFLD.

PMID- 21940338
TI  - CYP3A4*18 polymorphisms and anti-hepatitis A virus seroprevalence.
AB  - BACKGROUND/AIMS: CYP3A4 is the major cytochrome in humans which shows reduced
      activity in chronic liver disease as well as in hepatic cirrhosis. The detection
      of this polymorphism may give an indication on the prognosis of patients having
      chronic viral hepatitis with superimposed hepatitis A infection. The aim of this
      study is to correlate the seroprevalence of anti-HAV antibodies in chronic liver
      disease patients having CYP3A4*18 polymorphisms. METHODOLOGY: This is a
      prospective study where patients (n=119) blood was tested for anti-HAVIgG and
      CYP3A4*18 polymorphism. RESULTS: The overall anti-HAV seroprevalence was 88.2%.
      The etiology of CLD was hepatitis B in 96 patients (80.7%) and hepatitis C in 23
      patients (19.3%). There was a significant increase in the age of the prevalence
      of this disease after 30 years of age (p=0.008). CYP3A4*18 polymorphism was
      detected in 3 (2.5%) of the patients with chronic liver disease. However, there
      was no significant association between CP3A4*18 mutation and anti-HAV serology.
      CONCLUSIONS: Age was the most important factor in determining anti-HAV
      positivity. It is concluded that CYP3A4*18 genetic polymorphism does not play a
      main role in influencing the seroprevalence of anti-hepatitis A among chronic
      viral hepatitis B and C liver disease patients.

PMID- 21940339
TI  - Prognosis in patients with small hepatocellular carcinoma: a meta-analysis.
AB  - BACKGROUND/AIMS: To evaluate the impact of anatomic and non-anatomic liver
      resection on prognosis of patients with small hepatocellular carcinoma (HCC)
      using a meta-analysis. METHODOLOGY: Literature on anatomic versus non-anatomic
      liver resection for the treatment of small HCC published in public was retrieved.
      RESULTS: Four non-randomized controlled trials studies were included in this
      analysis. These studies included a total of 776 patients: 484 treated with
      anatomic liver resection and 282 treated with non-anatomic resection. No
      significant differences were found concerning the 1, 3 and 5-year disease-free
      survival rate between the two groups. There was no significant difference between
      the two groups when comparing the 1, 3 and 5-year overall survival rate. We use
      the sensitivity analysis which found anatomic resection could extend the 3-year
      disease-free survival rate when compared with non-anatomic resection (odds ratio
      (OR)=0.72, 95% confidence interval (CI): 0.52-0.99, p=0.04). CONCLUSIONS:
      Anatomic liver resection can extend the 3-year disease-free survival rate of
      patients with small hepatocellular carcinoma. Further randomized controlled
      trials are needed to define the exact value of anatomic resection and non
      anatomic resection for small HCC.

PMID- 21940340
TI  - Simultaneous measurements of serum AFP, GPC-3 and HCCR for diagnosing
      hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is a prevalent malignant tumor.
      Tumor markers are very useful in early diagnosis; however a single marker is
      rather limited. We launched a test to increase the diagnostic sensitivity through
      the combined detection. METHODOLOGY: Serum concentration of three tumor-markers,
      Glypican-3 (GPC-3), Human-Cervical-Cancer-Oncogene (HCCR) and a-fetoprotein
      (AFP), were determined in 189 samples: 101 cases of HCC, 40 cases of cirrhosis,
      18 cases of hepatitis and 30 cases of control healthy donors. Every marker was
      evaluated for its diagnostic value by one-way-analysis-of-variance and receiver
      operating-characteristics analysis. RESULTS: GPC-3 was the best marker with an
      area under the curve (AUC) of 0.892; using 26.8ng/mL as the cut-off for HCC
      diagnosis, GPC-3 has a sensitivity of 51.5% and maintains a specificity of 92.8%.
      HCCR, with an AUC of 0.831, can reach a sensitivity of 22.8% and maintain a
      specificity of 90.9% if the cut-off is set as 58.8mAU/mL. With an AUC of 0.827,
      the efficacy and sensitivity of AFP were 36.6% and 98.5% when using 199.3ng/mL as
      the cut-off. No significant correlation was found between these three markers.
      Simultaneously detecting three markers can significantly increases the
      sensitivity to 80.2%, much higher than AFP alone. CONCLUSIONS: GPC-3 and HCCR are
      useful tumor markers complementary to AFP for clinical diagnosis of HCC.

PMID- 21940341
TI  - Anti-viral therapy in chronic HBV infection: a single centre experience.
AB  - BACKGROUND/AIMS: Current treatment of HBV chronic infection is based on
      interferon (IFN) or nucleoside/nucleotide analogs (NUCs). Seroconversion and
      resistance rates were evaluated in 135 HBV patients treated with NUCs alone or
      NUCs+IFN, during the period 1999-2009. METHODOLOGY: Twenty-seven patients were
      treated with lamivudine (LAM group), 62 with LAM+IFN for 12 months, followed by
      lamivudine alone (LAM+IFN group). Patients developing lamivudine resistance were
      added adefovir (add-on) or switched to entecavir. The remaining 46 naive patients
      received entecavir (ETV group). RESULTS: HBsAg loss was 0% in the LAM and ETV
      groups, while it reached 8% in the LAM+IFN group. HBe/anti-HBe seroconversion was
      20% with NUCs alone but reached 66.6% with NUC+IFN. In the LAM group, resistance
      was 74% to lamivudine, 47% to adefovir (add-on) and 20% to entecavir (switch). In
      the LAM+IFN group, resistance to lamivudine was significantly lower in the first
      24 months of treatment, reaching 72% by 84 months. In the ETV group, no
      virological breakthrough was observed. CONCLUSIONS: Our findings suggest a higher
      percentage of HBe/anti-HBe seroconversion in patients treated with NUCs+IFN as
      compared to the data reported in the literature when administering interferon or
      NUCs alone, and substantially confirm the literature data on NUCs resistance.

PMID- 21940342
TI  - A new technique of lateral approach for laparoscopy-assisted donor left
      hepatectomy.
AB  - This report describes laparoscopy-assisted donor left hepatectomy preserving the
      caudate lobe (LADLH), and a new technique for hand-assisted liver transection
      between the left lobe and the caudate lobe beforehand, called the 'lateral
      approach.' Four donor patients underwent LADLH. Preoperative computed tomography
      investigated the depth and width between the left lobe and the caudate lobe from
      the Arantius duct. LADLH was performed through a 9cm midline epigastric hand-port
      incision with four ports. The confluence of the middle and left hepatic veins was
      encircled with tape. Hand-assisted liver transection between the left lobe and
      the caudate lobe was performed using laparosonic coagulating shears after
      precoagulation with radio frequency ablation under ultrasonographic guidance.
      Through the hand-port incision, the tape around the middle and left hepatic veins
      could be passed between the left lobe and the caudate lobe to the porta hepatis.
      We used the tape toward the end of the parenchymal transection to bring the
      transection plane closer to the surface. The liver parenchyma was divided at
      Cantlie's line under direct vision. The graft was extracted through the hand-port
      incision. All donors underwent LADLH completely without any intraoperative
      complication. None of the donors required transfusion or re-operation.

PMID- 21940343
TI  - Dexamethasone decreases hepatocellular carcinoma cell sensitivity to cisplatin
      induced apoptosis.
AB  - BACKGROUND/AIMS: Despite the fact that dexamethasone (DEX), a synthesized
      glucocorticoid (GCs), in vitro has pro-apoptotic effects on lymphoid cells, it
      has been suggested to induce apoptosis resistance toward chemotherapy in lung,
      cervical and breast cancer cell lines. However, the mechanisms by which GCs
      inhibit apoptosis in some cells have not been elucidated. The aim of this study
      is to investigate the effect of DEX on cisplatin (CIS)-induced hepatocellular
      carcinoma cell proliferation, apoptosis and to determine apoptosis-related gene
      expression on mRNA and protein levels. METHODOLOGY: MTT assay, annexin V-FITC as
      well as Hoechst33258 staining were performed to detect hepatocellular carcinoma
      cell proliferation and apoptosis, respectively. RT-PCR and western blot were used
      to determine Bcl-2 and Bcl-xL expression. RESULTS: DEX alone did not cause any
      obvious change to HepG2 and SNU449 cell proliferation. When pretreated with DEX
      followed by CIS treatment, cells showed resistance to CIS-induced cytotoxicity by
      MTT assay and apoptosis detected by Annexin V-FITC kit double staining.
      Hoechst33258 staining showed that CIS caused cell nuclear condensation, a sign of
      apoptosis and DEX pretreatment reduced the proportion of apoptotic cells. Anti
      apoptotic genes Bcl-2 and Bcl-xL expression levels decreased after CIS treatment,
      but increased again after DEX addition. CONCLUSIONS: DEX can decrease
      hepatocellular carcinoma cell sensitivity to CIS-induced cell death by preventing
      cell apoptosis.

PMID- 21940344
TI  - Transarterial embolization using pingyangmycin lipiodol emulsion and polyvinyl
      alcohol for the treatment of focal nodular hyperplasia of the liver.
AB  - BACKGROUND/AIMS: Surgical resection is the current treatment for focal nodular
      hyperplasia of the liver (FNH) when indicated. However, tumor location and size,
      patient comorbidities, and risk of complications may limit surgical options in
      some cases. Our goal was to evaluate the therapeutic effect of transarterial
      embolization (TAE) using pingyangmycin lipiodol emulsion (PLE) and polyvinyl
      alcohol particles to treat FNH. METHODOLOGY: Four patients with FNH, who
      experienced dull pain in the upper abdomen or liver area and confirmed by biopsy,
      were treated by TAE with PLE and polyvinyl alcohol (diameter: 500um-700um).
      Therapeutic effects including changes in lesion diameter and symptomatic
      improvement, and occurrence of complications, were evaluated for a follow-up
      period ranging from 12 to 42 months after the procedure. RESULTS: All of four
      patients were successfully treated with PLE and polyvinyl alcohol embolization.
      One month after the procedure, dull pain in the upper abdomen or liver area
      vanished completely. Follow-up examination by CT or MRI revealed complete
      resolution in two cases and an obvious decrease in the other two cases. No
      immediate or delayed postembolization complications were encountered. CONCLUSION:
      Transarterial embolization using PLE and polyvinyl alcohol should be considered
      as a safe and effective method for the treatment of FNH.

PMID- 21940345
TI  - The clinical relevance of the expression of the ratio of laminin-5 subchains
      messenger RNA of hepatocellular carcinoma to non-cancerous liver remnant: a
      prospective study.
AB  - BACKGROUND/AIMS: Laminin-5 has been reported as a prognostic indicator of some
      malignancies. This prospective study aimed to elucidate the correlation between
      the ratio of the expression of different laminin-5 subchain mRNAs in HCC tissue
      and the clinical relevance or prognosis of patients. METHODOLOGY: Using RT-PCR,
      a3, beta3 and ?2 mRNA levels were determined prospectively from 29 patients with
      HCC undergoing curative resection. The ratio of the value of each subchain mRNA
      in HCC tissue to non-cancerous liver tissue was measured. RESULTS: The mRNA of
      a3, beta3 and beta2 was detected in both HCC tissue and the liver remnants in 29
      (100%), 29 (100%) and 28 (96.5%) patients, respectively. The ratio of ?2 mRNA
      correlated with the absence of complete encapsulation (p=0.033) and with the
      presence of hepatitis, with borderline significance (p=0.081). The ratio of a3
      mRNA correlated with tumor hemorrhage and tumor necrosis with borderline
      significance (p=0.082 and p=0.082, respectively). The ratios of a3, beta3 and ?2
      mRNA did not correlate significantly with postresection recurrence, recurrence
      and patient survival. CONCLUSIONS: Expression of a3, beta3 and ?2 cannot predict
      the prognosis. However, high expression of ?2 mRNA in HCC/non-cancerous liver
      correlated significantly with the absence of complete encapsulation, which is an
      important tumor invasiveness factor.

PMID- 21940347
TI  - Transoralgastric gastroscopic debridement for peripancreatic abscess: a special
      case report.
AB  - Transoralgastric debridement for pancreatic abscess is one of the successful
      applications of NOTES in clinical practice. We present a case report as follows:
      a 71-year-old female was hospitalized due to acute biliary pancreatitis. Three
      weeks after onset, the secondary abdominal CT showed a peripancreatic abscess. A
      passageway between the gastric wall and the abscess was made with a high
      frequency puncher under the guidance of an ultrasonic gastroscope and then a
      gastroscope was directly inserted into the abscess, and a large amount of solid
      necrotic tissue was taken out with foreign body forceps and snare under the
      direct vision of a gastroscope. Then a 8.5F double-J stent and a nasobiliary
      drainage tube were inserted. After three times of intra-abdominal abscess
      debridement and repeated rinsing with an antibiotic solution, abdominal CT
      revealed the intra-abdominal abscess nearly disappeared and the patient
      discharged from hospital.

PMID- 21940346
TI  - Ribonucleotide reductase M1 expression in intrahepatic cholangiocarcinoma.
AB  - BACKGROUND/AIMS: Ribonucleotide reductase M1 (RRM1) is a key molecule for
      gemcitabine resistance. This study evaluated the immunohistochemical expression
      of RRM1 in resected specimens of intrahepatic cholangiocarcinoma (ICC) and
      investigated the efficacy of gemcitabine-based neoadjuvant chemotherapy in
      relation to RRM1 expression in tumors. METHODOLOGY: A retrospective analysis was
      conducted on 34 consecutive Japanese patients who underwent resection of ICC. Of
      the 34 patients, 2 were treated with neoadjuvant chemotherapy consisting of
      gemcitabine 800mg/m2 every 2 weeks to address extrahepatic tumor extension.
      Expression of RRM1 in tumor specimens was assessed using immunohistochemistry and
      was classified as either positive or negative. RESULTS: RRM1-positive expression
      was detected in 19/34 (56%) tumor specimens. Two patients were treated with
      gemcitabine-based neoadjuvant chemotherapy; one had a tumor specimen showing RRM1
      positive expression and showed a 14% tumor reduction rate (stable disease);
      another patient had a tumor showing RRM1-negative expression and showed a 68%
      tumor reduction rate (partial response). Surgical procedures planned before
      administration of neoadjuvant chemotherapy were performed in both patients.
      CONCLUSIONS: Neoadjuvant chemotherapy with gemcitabine for locally advanced ICC
      was well tolerated and did not impair planned surgical resections. Tumor
      expression of RRM1 may determine the efficacy of gemcitabine-based chemotherapy
      for patients with ICC.

PMID- 21940348
TI  - Survival benefit with the combination of docetaxel, gemcitabine and erlotinib in
      advanced and/or metastatic pancreatic cancer patients.
AB  - BACKGROUND/AIMS: Although research on new effective treatments against pancreatic
      cancer is intense, limited therapeutic schemes are currently approved. The aim of
      the present study was to record the efficacy and safety of gemcitabine-erlotinib
      plus docetaxel combination therapy in patients with advanced and/or metastatic
      pancreatic cancer. METHODOLOGY: Twenty-five chemotherapy naive patients with
      histologically confirmed unresectable pancreatic cancer and documented
      extrapancreatic metastases, received biweekly gemcitabine 1,500mg/m2 during a 28
      day long cycle; daily erlotinib 100mg per os; and docetaxel 80mg/m2 as
      intravenous infusion administered every 15 days. Patients were monitored every 4
      cycles for survival, adverse events and tumour response with Computed Tomography
      scans. RESULTS: Patients received 153 cycles in total, with a median of 7.64
      cycles (range, 1-24). The median overall survival was 10 months and 45% of the
      patients reached and surpassed 1-year survival. No grade IV toxicities were
      recorded. The only grade III recorded toxicities were thrombopenia (4 patients,
      16%), anaemia (1 patient, 4%) and neutropenia (1 patient, 4%). Overall the most
      frequently experienced adverse events were grade I anaemia (18 patients, 72%) and
      grade II rash (13 patients, 52%). CONCLUSIONS: Biweekly gemcitabine with
      erlotinib plus docetaxel administration is a practical alternative to pancreatic
      cancer treatment, presenting comparable results to weekly gemcitabine
      administration.

PMID- 21940349
TI  - Protection of major vessels and pancreaticogastrostomy using the falciform
      ligament and greater omentum for preventing pancreatic fistula in soft pancreatic
      texture after pancreaticoduodenectomy.
AB  - BACKGROUND/AIMS: Pancreatic fistula is one of the major causes of morbidity in
      patients undergoing pancreaticoduodenectomy. Protection of the skeletonized
      vessels and the anastomotic site of pancreaticoenterostomy is one of the surgical
      options to prevent the development of a pancreatic fistula. The aim of this study
      was to describe an operative technique to protect the vessels and anastomotic
      site by wrapping them with the falciform ligament and the greater omentum.
      METHODOLOGY: After a modified subtotal stomach-preserving pancreaticoduodenectomy
      reconstruction with pancreaticogastrostomy was performed, the falciform ligament
      and greater omentum was used on the skeletonized major vessels and wrapped around
      the anastomotic site of pancreaticogastrostomy. Twenty consecutive patients were
      enrolled in this prospective study. RESULTS: The entire procedure did not result
      in any operative complications. Postoperative pancreatic fistula developed in 2
      cases (10%). According to the international postoperative pancreatic fistula
      criteria, grade A and grade B was observed in 1 case each. No intra-abdominal
      hemorrhage and late intra-abdominal abscess were observed. CONCLUSIONS: This
      procedure is a convenient and safe technique, and may be helpful in preventing
      major complications caused by pancreatic fistula.

PMID- 21940350
TI  - Clinicopathological characteristics of intrahepatic cholangiocarcinoma in
      patients with cirrhosis.
AB  - BACKGROUND/AIMS: The purpose of this study was to explore the clinicopathological
      characteristics of intrahepatic cholangiocarcinoma (ICC) in patients with
      cirrhosis. METHODOLOGY: A total of 155 patients with ICC were divided into those
      with cirrhosis (n=52) and those without cirrhosis (n=103). We compared the
      clinicopathological features of patients in both groups. RESULTS: The prevalence
      of HBsAg seropositivity and hepatolithiasis in ICC patients with cirrhosis was
      higher than that in patients without cirrhosis. Compared with noncirrhotic
      patients, cirrhotic patients had a higher incidence of reduced albumin (46.1% vs.
      25.2%, p<0.008) and elevated total bilirubin (TBIL) levels (44.2% vs. 24.3%,
      p=0.011). The resectability rate in cirrhotic patients was lower than that in
      noncirrhotic patients (63.7% vs. 80.6%, p=0.033). CONCLUSIONS: Among ICC
      patients, we found marked differences in clinicopathological characteristics and
      therapeutic approaches between cirrhotic and noncirrhotic patients. ICC patients
      with cirrhosis may have poorer prognosis than those without cirrhosis.

PMID- 21940351
TI  - Mining predictive biomarker for neoadjuvant chemotherapy in gastric cancer by
      proteomics.
AB  - BACKGROUND/AIMS: In this study, we applied the SELDI-TOF-MS technique for the
      identification of gastric cancer-specific protein markers and sample SELDI
      protein profiling to distinguish gastric cancer patients of the efficacy of
      neoadjuvant chemotherapy from a no efficacy population. METHODOLOGY: Gastric
      tissue samples from 8 paired patients with gastric cancer, from whom clinical and
      histopathological data concerning patients and carcinomas were available, were
      analyzed. We scanned 8 paired samples (chemotherapy sensitive and insensitive) by
      SELDI-TOF-MS. RESULTS: The data generated 409 high sensitive and reproducibly
      peaks. From the distribution of the peaks, most of the detectable peaks are in
      the range from 3000-7000m/z. One potential protein at 7044m/z is Guanine
      nucleotide-binding protein (GBG7_Human 060262). CONCLUSIONS: In summary, we
      present novel differential expressed protein profile for neoadjuvant
      chemotherapy. This data set will help us to understand the mechanism for the
      chemotherapy resistance. Our data suggested the presence of GBG7 indicate patient
      will receive better prognosis of neoadjuvant chemotherapy.

PMID- 21940352
TI  - Pattern of surgical treatment for early gastric cancers in upper third of the
      stomach.
AB  - BACKGROUND/AIMS: Various surgical treatments are indicated for early gastric
      cancers in upper third of the stomach (U-EGC) because of its anatomical property
      and favorable prognosis. METHODOLOGY: Five hundred and eighty six cases of U-EGCs
      were collected for 9 years from 19 hospitals in Japan. Surgical procedures were
      classified as total (TG) and proximal gastrectomy (PG), and the latter was
      subclassified as esophagogastrostomy (PG-EG) and jejunal interposition (PG-JI)
      reconstruction. RESULTS: TG was more frequent than PG (76.3% vs. 21.8%,
      p<0.0001). PG was more frequently performed in high volume hospitals than in low
      volume hospitals (26.8% vs. 10.2%, p<0.0001), however there were still large
      difference in frequency of PG even among high volume hospitals, ranging from 5.0%
      to 72.0%. For reconstruction after PG, PG-EG and PG-JI were representatively
      performed in 50 (39.1%) and 35 (27.3%) patients. Each institute tended to
      preferentially employ either PG-EG or PG-JI. Tumor size was significantly larger
      in TG than in PG (38.8mm vs. 22.3mm, p<0.0001) and diffuse type tended to be more
      frequent in TG as well. CONCLUSIONS: There is a huge variety of surgical
      treatment for U-ECG in general hospitals in our country. A multi-institutional
      large cohort randomized trial might be urgent to establish the standard surgical
      procedure of this infrequent disease.

PMID- 21940353
TI  - Correlation between plasma or mucosal ghrelin levels and chronic gastritis.
AB  - BACKGROUND/AIMS: The aim of this study was to clarify the relationship between
      plasma or mucosal ghrelin levels and endoscopic or histological severity, acid
      secretion and H. pylori infection associated with chronic gastritis. METHODOLOGY:
      We measured plasma and mucosal ghrelin levels in 80 consecutive individuals with
      chronic gastritis, including 51 H. pylori-positive and 29 H. pylori-negative
      subjects. The topographic distribution of gastritis was divided into open type
      and closed type. During endoscopy, five adjacent biopsy specimens were obtained
      from the antrum, corpus and angulus. Using the updated Sydney System,
      histological parameters including activity, chronic inflammation, glandular
      atrophy and intestinal metaplasia were graded. Mucosal ghrelin, fasting plasma
      ghrelin, serum pepsinogen I and II, gastrin and H. pylori infection were all
      measured. RESULTS: All four measured histological parameters were significantly
      higher in H. pylori-positive patients than in H. pylori-negative patients. Serum
      pepsinogen I and II levels were also significantly higher in the H. pylori
      positive group. Plasma and mucosal ghrelin levels correlated well with the
      topographic distribution of gastritis, and also with histological parameters of
      glandular atrophy in the corpus and angulus of the stomach. CONCLUSIONS: Plasma
      and mucosal ghrelin levels may reflect the extent of atrophy in the stomach
      irrespective of the presence of H. pylori infection, which is closely associated
      with the development of chronic gastritis.

PMID- 21940354
TI  - Tissue and serum adiponectin levels in patients with gastric cancer: are there
      any correlations between adiponectin levels and histopathological variables?
AB  - BACKGROUND/AIMS: Adiponectin is secreted from adipose tissue and is characterized
      by hyperinsulinemia, which is related with obesity. Adiponectin levels are
      significantly lower in gastric cancer patients than in healthy controls. The aim
      of this study was to investigate the relationship between adiponectin levels in
      serum, tumor tissue and normal tissue with some other insulin resistance
      parameters. METHODOLOGY: A total of 35 patients with gastric cancer who had
      undergone curative gastrectomy by standard lymph node dissection were enrolled in
      this study. Their serum adiponectin levels, tumor tissue and normal breast tissue
      adiponectin levels were compared. RESULTS: The mean adiponectin levels of the
      tumor tissue, normal gastric tissue and serum were 48.6+/-2.9 (range, 39.7-50.6),
      48.3+/-4.2 (range, 34.4-50.69) and 49.4+/-0.83 (range, 48.2-50.2), respectively.
      There was no relationship between the adiponectin levels in serum, normal tissue
      and tumor tissue (p=0.08). There was an inverse relationship between normal
      tissue adiponectin levels and insulin levels (p=0.002, r=-0.5), but this
      association was not detected with adiponectin levels in tumor and serum (p>0.05).
      CONCLUSIONS: Relationships between adiponectin levels in serum, normal tissue and
      tumor tissue for gastric cancer patients were not found. The small sample size in
      this study may have influenced the results. However, we believe that our results
      constitute a first in evaluating the tissue adiponectin levels in gastric cancer
      tissue.

PMID- 21940355
TI  - Effects of paxillin on HCT-8 human colorectal cancer cells.
AB  - BACKGROUND/AIMS: The aim of this study was to investigate the effects of paxillin
      on proliferation, migration, invasion, adhesion and apoptosis of HCT-8 human
      colorectal cancer cells in vitro. METHODOLOGY: siRNA plasmids, overexpression
      wild-type plasmids and overexpression mutant plasmids were generated and
      transfected into HCT-8 cells. The expression of paxillin mRNA and protein was
      analyzed, and cell proliferation and adhesion were measured. Flow cytometry was
      used for cell sorting and detection of cell apoptosis. The invasive ability of
      HCT-8 cells was also observed. RESULTS: The proliferation, migration and invasive
      capacity of the HCT-8 cells transfected with siRNA paxillin plasmids were
      inhibited. Overexpression of wild-type paxillin plasmids promoted cell
      proliferation and also enhanced migration, invasive capacity and metastasis of
      the cancer cells. Overexpression of mutant paxillin plasmids inactivated the
      function of phosphorylation, inhibited cell migration and invasion capacity, but
      cell adhesion and proliferation had no significant difference compared with the
      normal group. CONCLUSIONS: These findings suggest that paxillin may play an
      essential role in the progression of colorectal cancer and RNAi targeting of
      paxillin may be a potential therapeutic strategy for the treatment of colorectal
      cancer.

PMID- 21940356
TI  - Arterial stimulation and venous sampling for glucagonomas of the pancreas.
AB  - BACKGROUND/AIMS: Arterial stimulation and venous sampling (ASVS) is a catheter
      based diagnostic technique used to identify the localization of an insulinoma or
      gastrinoma. The aim of this study was to clarify the clinical significance of
      ASVS for glucagonomas. METHODOLOGY: Eight patients with pancreatic hypervascular
      tumors and elevated serum glucagon levels in the peripheral blood were enrolled.
      Pancreatic angiography was performed and a bolus dose of calcium was injected
      into a suitable artery. Hepatic venous blood samples were then obtained to
      measure concentrations of glucagon and insulin. All patients underwent surgical
      resection, and the resected specimens were investigated immunohistochemically.
      RESULTS: Compared to insulin, the glucagon levels stabilized after calcium
      stimulation in four patients, with a 1.2-fold increase or decrease. In the
      remaining four patients, there was a 1.6- to 5.8-fold increase in glucagon
      levels. The peak value of glucagon was observed at 90s or 120s which was slower
      than the insulin peak observed in patients with insulinoma. The patients with
      elevated glucagon levels during ASVS exhibited positive immunostaining of
      glucagon in resected specimens. CONCLUSIONS: Increase in glucagon after calcium
      stimulation was observed in patients with glucagonomas. ASVS for glucagonomas may
      be useful in determining the most suitable surgical procedure.

PMID- 21940357
TI  - Risk factors of ascites after hepatectomy for patients with hepatocellular
      carcinoma and hepatitis B virus-associated cirrhosis.
AB  - BACKGROUND/AIMS: To identify risk factors of postoperative ascites after
      hepatectomy for patients with hepatocellular carcinoma (HCC) and hepatitis B
      virus associated-cirrhosis. METHODOLOGY: The data of 73 patients were reviewed in
      current study. Pre- and intra-operative variables were retrospectively analyzed
      using uni- and multi-variate analyses. The diagnostic accuracy of the predictors
      was evaluated by the receiver operating characteristics (ROC) analysis. RESULTS:
      Indocyanine green retention rate at 15 minutes (ICGR15) >10%, tumor size >10cm,
      splenectomy, middle hepatic vein (MHV) resection, red blood cell (RBC)
      transfusion were risk factors in univariate analysis. However, only ICGR15 >10%,
      tumor size >10cm and RBC transfusion showed prognostic power in multivariate
      analysis. ROC analysis suggested the best cut-off value of risk factors was 2.
      CONCLUSIONS: Our study indicated the postoperative ascites could be predicted by
      pre- and intra-operative variables. ICGR15 >10%, tumor size >10cm and RBC
      transfusion were independent risk factors for ascites after hepatectomy. Patients
      with two or more of the above-mentioned risk factors may suffer postoperative
      ascites after hepatectomy.

PMID- 21940358
TI  - Lateral pelvic lymph node dissection using latero-vesical approach with
      aspiration procedure for advanced lower rectal cancer.
AB  - BACKGROUND/AIMS: The aim of this study was to evaluate the impact of complete
      dissection of areolar tissue surrounding lymph nodes in lateral pelvic
      lymphadenectomy on the outcome of advanced rectal cancer at or below the
      peritoneal reflection. METHODOLOGY: From 1995 to 2004, lateral pelvic lymph node
      dissection was performed in 141 consecutive patients with advanced rectal cancer
      at or below the peritoneal reflection by open surgery in our hospital. They were
      divided into two groups according to the techniques used for lymph node
      dissection, i.e. conventional method (CM) and our original method, latero-vesical
      approach with aspiration procedure (LVA), which eliminates not only lymph nodes
      but also the tissue surrounding the lymph nodes. RESULTS: The number of dissected
      lateral pelvic lymph nodes by LVA was significantly higher than that by CM. In
      patients without lateral pelvic lymph node metastasis, no significant difference
      in the outcome was observed between the two groups. On the contrary, among the
      patients with lateral pelvic lymph node metastasis, five-year survival rates of
      the group with CM or with LVA was 50% and 70% respectively. CONCLUSIONS: For
      patients with lateral pelvic lymph node metastasis, lateral pelvic
      lymphadenectomy, complete dissection of areolar tissue surrounding lymph nodes,
      may contribute to improve the prognosis of advanced rectal cancer at, or below,
      the peritoneal reflection.

PMID- 21940359
TI  - Impact of grading of liver metastasis on postoperative outcome in patients with
      liver metastases from colorectal cancer.
AB  - BACKGROUND/AIMS: Few studies have investigated grading of liver metastasis (GLM)
      in patients with liver metastases from colorectal cancer (LM-CRC). METHODOLOGY:
      To screen for the most useful predictive factors in patients undergoing hepatic
      resection for LM-CRC, clinico-pathological factors were subjected to uni- and
      multivariate analyses. RESULTS: One hundred and twenty-five patients were
      evaluated retrospectively. Univariate analyses using clinico-laboratory factors
      demonstrated that nomogram, gender, CRP, albumin, number of hepatic resections,
      liver metastasis (H) and GLM were related to postoperative death. Multivariate
      analysis using these seven factors disclosed that albumin (OR, 6.949; 95% CI,
      1.994-24.22; p=0.002), CRP (OR, 6.977; 95% CI, 1.937-25.14; p=0.003) and GLM (OR,
      2.819; 95% CI, 1.082-7.346; p=0.034) were associated with postoperative death.
      Kaplan-Meier analysis and log rank test revealed that higher GLM (p<0.001) and
      CRP (p<0.001) were associated with a higher rate of postoperative death. GLM was
      able to divide the patients into three independent groups with significantly
      different total nomogram counts (p<0.001, Kruskal-Wallis test). CONCLUSIONS: GLM
      is able to classify patients with LM-CRC into three independent groups and offers
      reliable information for predicting postoperative death in such patients.

PMID- 21940360
TI  - Ano-neorectal function using manometry on patients after restorative
      proctocolectomy and ileal J-pouch anal anastomosis for ulcerative colitis in
      children.
AB  - BACKGROUND/AIMS: The purpose of this study was to clarify the ano-neorectal
      functions in pediatric patients with soiling at a short period and without
      soiling at a long period after restorative colectomy and ileal J-pouch anal
      anastomosis (IPAA) for ulcerative colitis (UC). METHODOLOGY: Ten patients after
      IPAA for UC in childhood were mamometrically studied, aged 10 to 16 years (mean,
      13.9 years). Patients after IPAA with ileostomy closure were studied at 6 months
      (Group A; all patients had soiling) and 3 years after ileostomy closure (Group B;
      all patients showed continence). Group C served as controls and consisted of 12
      subjects (aged 12 to 16 years, mean, 14.8). RESULTS: Maximum anal sphincter
      pressure at rest and maximum anal sphincter pressure during voluntary contraction
      were significantly lower in group A than in groups B and C. Minimum neorectal
      sensory threshold volume in group A was significantly higher than in groups B and
      C (p<0.01). Maximum neorectal tolerated threshold volumes and neorectal
      compliances, and positive rates of neorectoanal inhibitory reflex, showed no
      significant difference among the groups. CONCLUSIONS: Patients with soiling at 6
      months after IPAA showed anal sphincter dysfunction and neorectal sensory
      dysfunction. The IPAA may cause damage to the ano-neorectal apparatus during
      rectal mobilization due to the short rectal cuff and mucosectomy.

PMID- 21940361
TI  - Predictive value of expression of ERCC 1 and GST-p for 5-fluorouracil/oxaliplatin
      chemotherapy in advanced colorectal cancer.
AB  - BACKGROUND/AIMS: The aim of this study was to determine whether expression of the
      excision repair cross complementing protein (ERCC1), glutathione S-transferase pi
      (GST-p) and thymidylate synthase (TS) predict response in patients with advanced
      colorectal cancer treated with 5-fluorouracil/oxaliplatin chemotherapy.
      METHODOLOGY: The study population consisted of 39 patients with advanced
      colorectal cancer (median age, 65 years). Patients were treated with the modified
      FOLFOX 6 regimen. The expression of ERCC-1, GST-p and TS of primary tumors were
      examined by immunohistochemistry. RESULTS: The response rate of modified FOLFOX 6
      chemotherapy was 51.3%. The positive rates of ERCC-1, GST-p and TS were 43.6%,
      33.3% and 66.7%, respectively. The patients without ERCC-1 (p=0.0248) or GST-p?
      (p=0.0019) expression were more likely to respond to chemotherapy. TS expression
      did not correlate with chemotherapeutic response. CONCLUSIONS:
      Immunohistochemical studies for ERCC-1 and GST-p may be useful in prediction of
      the response to 5-fluorouracil/oxaliplatin chemotherapy in advanced colorectal
      cancer patients.

PMID- 21940362
TI  - The effect of terlipressin on hepatic hemodynamics in small-for-size livers.
AB  - BACKGROUND/AIMS: The aim of this study was to investigate the effect of
      terlipressin on hepatic hemodynamics in small-for-size livers at early phase
      after major hepatectomy. METHODOLOGY: Thirty-six rats were divided into treatment
      group (Group Th) and control group (Group Ch) for hemodynamic study. Hepatic
      hemodynamic parameters were detected before hepatectomy (baseline values), 30min,
      1h, and 2h after reperfusion. Twenty rats were divided into the treatment group
      (Group Ts) and control group (Group Cs) for survival study. The survival rate and
      hemodynamic parameters were studied. RESULTS: The 10-day survival rate of the Ts
      group was significantly higher than that of the Cs group (p<0.05). The portal
      pressure of Group Th1/2 was significantly lower than that of Group Ch1/2
      (p<0.05). Portal pressure of Group Th1 was significantly lower than that of Group
      Ch1 (p<0.05). The portal blood flow of Group Th1/2 was significantly lower than
      that of Group Ch1/2, and so was that between Group Th1 and Ch1, (both p<0.05).
      The portal blood flow of Group Ch1/2 was significantly higher compared to its
      baseline value (p<0.05). CONCLUSIONS: The survival rate of rats with small-for
      size liver can be significantly improved by terlipressin. Terlipressin
      ameliorates portal hyperperfusion in small-for-size liver by effectively reducing
      portal pressure and portal blood flow at early phase after hepatectomy.

PMID- 21940363
TI  - A modified pancreaticojejunostomy: kissing pancreaticojejunostomy.
AB  - Pancreaticoduodenectomy (Whipple procedure) has been the standard treatment for
      periampullary and pancreatic carcinoma. A leakage or fistula from the pancreatic
      anastomosis is the leading cause of morbidity and mortality after
      pancreaticoduodenectomy. In order to prevent the development of pancreatic
      fistula, we designed a modified pancreaticojejunostomy called Kissing
      Pancreaticojejunostomy, by which the pancreatic tube was tightly in touch with
      (kissing) the jejunal mucosa via a tent tube. We have performed this procedure on
      71 consecutive patients and only one patient developed pancreatic fistula. It is
      a safe, simple and efficient technique.

PMID- 21940364
TI  - Withdrawal times affects polyp and diverticulum detection on the right-side
      colon.
AB  - BACKGROUND/AIMS: We aimed to investigate the association between colorectal polyp
      detection rates and withdrawal times, and also to investigate diverticulum
      detection rates as a counterpart lesion. METHODOLOGY: Thirteen trainee
      colonoscopists were characterized by their mean withdrawal time for normal colon.
      A total of 2,314 colonoscopies were analyzed. RESULTS: The mean withdrawal times
      ranged from 6.5 to 10.4 minutes among colonoscopists. Polyp detection rates in
      individual endoscopists ranged between 36.5% and 60.0%. When stratified by the
      hood use, a significant association was shown when the hood was not used
      (p=0.03), whereas no association was found when the hood used. On the other hand,
      diverticulum detection rates varied from 20.7% to 43.2%. A strong association was
      shown only when the hood was not used (p=0.009). CONCLUSIONS: An association
      between the polyp or diverticulum detection rate and the withdrawal time was
      observed when the transparent hood was not attached, and mainly on the right-side
      colon.

PMID- 21940365
TI  - Functional polymorphisms in FAS/FASL system contribute to the risk of occurrence
      but not progression of gastric cardiac adenocarcinoma.
AB  - BACKGROUND/AIMS: Loss of FAS and gain of aberrant FASL expression are common
      features of malignant transformation. This study was designed to investigate
      whether the functional polymorphisms of FAS-1377 G/A (rs2234767) and FASL-844 T/C
      (rs763110) have an effect on the occurrence and progression of gastric cardiac
      adenocarcinoma (GCA). METHODOLOGY: Associations of the FAS and FASL polymorphisms
      with GCA were estimated by OR and their 95% confidence intervals using logistic
      regression. RESULTS: In this study, as compared with the wild type homozygote and
      heterozygote, either the FAS-1377 AA or FASL-844 CC genotype was associated with
      increased risk of GCA (OR=1.78; 95% CI, 1.19-2.64 and OR=1.92; 95% CI, 1.46-2.54,
      respectively). Furthermore, individuals with both the FAS-1377 AA and FASL-844 CC
      genotypes have a higher risk of GCA (OR=4.09; 95% CI, 2.27-7.37) compared to
      those with the FAS-1377 GG and FASL-844 TT genotypes. Moreover, the FAS-1377 AA
      genotype increased the risk of GCA among smokers (OR=1.88; 95% CI, 1.11-3.20) but
      not among non-smokers, suggesting a potential gene-smoking interaction.
      CONCLUSIONS: This current study suggests that functional polymorphisms in the
      apoptotic pathway genes FAS and FASL may significantly contribute to the
      occurrence of GCA.

PMID- 21940366
TI  - Contralateral glissonian pedicle occlusion in a case of portal vein tumor
      thrombosis.
AB  - To dissect portal vein branches directly and encircle them separately is a common
      procedure that is performed to control back flow bleeding during operations for
      hepatocellular carcinoma with portal vein tumor thrombosis. However, this
      technique has an increased risk of injuring contralateral portal branches and
      disseminating thrombosis fragments to the remnant liver. We present an
      alternative technique using right-sided glissonian pedicle occlusion for
      hepatocellular carcinoma with left portal vein tumor thrombosis due to complex
      anatomical vasculatures of the hepatic pedicle. This technique would be very
      useful for liver resection of hepatocellular carcinoma with the major type of
      portal vein tumor thrombosis.

PMID- 21940367
TI  - Single nucleotide polymorphism of multidrug-resistance 1 and anti- multidrug
      resistance 1 single chain antibody treatment for the pancreatic cancer cell line.
AB  - BACKGROUND/AIMS: Anticancer drugs are essential to pancreatic cancer therapy. The
      multidrug-resistance 1 (MDR1) gene codes for one of the ATP binding cassette
      (ABC) transporters. The neutralizing antibody of MDR1 reduces the activity of
      MDR1 and may add to the sensitivity of anti-cancer drugs. We investigated the
      relationship of the single nucleotide polymorphisms (SNPs), 2677G and 3435C, in
      the MDR1 gene and the effect of the anti-MDR1 single chain antibody (scAb) using
      pancreatic cancer cell lines. METHODOLOGY: We exposed the pancreatic cancer cell
      lines, AsCP-1, Panc-1, BxPC-3, MIAPaCa-2 and QGP-1 to 0.1-1,000u g/mL of 5-FU for
      72h and calculated the cytotoxic reactions. Combined therapy with an established
      anti-MDR1 neutralizing scAb and 10ug/mL of 5-FU was also performed. RESULTS: AsCP
      1 contained wild types of MDR1 2677G and 3435C, and showed the most 5-FU
      resistance. The anticancer effect of AsPC-1 increased with anti-MDR1 scAb, but
      the effect was not significant compared with other cell lines. CONCLUSIONS: The
      cells with the wild type SNPs of MDR1 showed drug resistance, but we were not
      able to confirm a remarkable effect of the anti-MDR1 antibody.

PMID- 21940368
TI  - Ribavirin dose and treatment outcome of Korean patients with genotype 1 chronic
      hepatitis C.
AB  - BACKGROUND/AIMS: The current recommendation of ribavirin dose for the treatment
      of chronic hepatitis C is based on study results of Western patients, and might
      not be optimal for Korean patients because of different body frames. METHODOLOGY:
      A total of 163 treatment-naive genotype 1 chronic hepatitis C patients who
      received combination therapy with pegylated interferon a-2a and ribavirin were
      reviewed. RESULTS: Under current ribavirin dosing, only 49% of patients started
      therapy with ribavirin dose of 13-15mg/kg (targeted dose), while 45% and 6% of
      patients started therapy with ribavirin dose =16mg/kg and <13mg/kg, respectively.
      Patients who started therapy with higher ribavirin dose experienced more
      ribavirin dose modification during treatment (55%, 31% and 11% for ribavirin dose
      of =16mg/kg, 13-15mg/kg and <13mg/kg, respectively, p=0.002). The sustained
      virological response (SVR) rate was 66%, 63% and 56% for ribavirin dose of
      =16mg/kg, 13-15mg/kg and <13mg/kg, respectively (p=0.775). CONCLUSIONS: A certain
      proportion of Korean patients started therapy with a higher than targeted
      ribavirin dose, which resulted in more ribavirin dose modifications without
      definite additional benefit in achieving SVR. Therefore, the ribavirin dosing
      regimen might need to be reassessed.

PMID- 21940369
TI  - Percutaneous transhepatic cholecystostomy for choledocholithiasis with acute
      cholangitis in high-risk patients.
AB  - BACKGROUND/AIMS: To evaluate the safety and feasibility of percutaneous
      transhepatic cholecystostomy for choledocholithiasis with acute cholangitis in
      high-risk patients. METHODOLOGY: Six high-risk patients of choledocholithiasis
      complicated with moderate to severe acute cholangitis underwent percutaneous
      transhepatic cholecystostomy and subsequent interval open surgery from January,
      2008 to October 2010. These patients, who were not suitable for both endoscopic
      and transhepatic biliary drainage, were reviewed retrospectively. RESULTS:
      Percutaneous transhepatic cholecystostomy was performed uneventfully. One patient
      developed hemoperitoneum which was successfully controlled by conservative
      treatment. Biliary peritonitits occurred in two patients, one ceased to leak
      spontaneously, the other developed a biloma which was cured by repuncture. No
      procedure-related death occurred. Sepsis was relieved completely 3 to 4 days
      after procedure. Two patients underwent interval open exploration of the common
      bile duct. One patient who recovered from sepsis succumbed on day 12 post
      cholecystostomy because of an acute cardiac infarct. The other 3 patients were
      cured of sepsis and discharged without further treatment. CONCLUSIONS: The
      results showed that ultrasound-guided percutaneous transhepatic cholecystostomy
      is a safe and effective procedure for choledocholithiasis with moderate to severe
      acute cholangitis in highly selected high-risk surgical patients. It may deserve
      to become a definitive therapy for subsequent surgical management. Larger
      controlled studies are needed to further confirm our findings.

PMID- 21940370
TI  - Surgical advantages of gastric SMTs by laparoscopy and endoscopy cooperative
      surgery.
AB  - BACKGROUND/AIMS: The treatment of gastric submucosal tumors (SMTs) is strictly
      surgical and enucleation of the tumor or wedge resection of the stomach is
      efficient to achieve R0 resection. Laparoscopic and endoscopic cooperative
      surgery (LECS) can be safely performed with adequate cutting lines. This study
      describes the initial 16 cases treated by LECS and evaluates the advantages by
      LECS for gastric SMTs retrospectively. METHODOLOGY: Sixteen patients with gastric
      SMT underwent LECS from June 2007 to December 2010, their surgical data, clinical
      characteristics and surgical specimens of SMTs were compared. The surgical
      specimens of 9 gastric SMTs treated by laparoscopic wedge resection (LWR) were
      compared as a control. RESULTS: The median (range) length of operation time,
      blood loss, hospital stay after surgery were minutes 172 (115- 220), <5mL (<5
      115) and 10 days (6-17), respectively. The median (range) ratio of the longest
      diameter of the tumor divided by the longest diameter of the surgical specimen in
      LECS and LWR were 0.86 (0.625-1.0) and 0.69 (0.44-1.0), respectively (p=0.0189,
      Wilcoxon rank sum test). CONCLUSIONS: LECS minimizes the surgical specimen while
      still providing sufficient surgical margins to successfully cure gastric SMTs.

PMID- 21940371
TI  - Results of a phase 4 trial of Tacrobell(r) in liver transplantation patients: a
      multicenter study in South Korea.
AB  - BACKGROUND/AIMS: This 26-week pilot study was performed in de novo liver
      transplant recipients to evaluate the efficacy of tacrobell capsule as an
      immunosuppressant drug after living donor liver transplant patients by
      determining the rate of acute cellular rejection after its use and evaluating its
      safety after transplantation. METHODOLOGY: From October 2005 to July 2007, 57
      patients from four major medical centers in Seoul, South Korea were enrolled in
      the study. This open-label, noncomparative, multicenter pilot study lasted 26
      weeks and assigned patients to receive tacrobell and corticosteroid after liver
      transplantation. Tacrobell (0.05mg/ kg/day, bid) and methylprednisolone were
      injected either on the day of the operation or on postoperative day one. A
      retrospective matched control group consisting of living donor liver transplant
      recipients at one center (Asan medical center) was used for comparison. RESULTS:
      The rate of acute cellular rejection with Tacrobell after 26 weeks of
      administration was 0.0% (95% CI, 0.0%-6.27%), which was below our hypothesized
      36%. The most common drug-related adverse events included endocrine/nutritional
      disorders followed by gastrointestinal and hepatobiliary disorders. No patients
      died during the study period. The side effect profile of this drug was no
      different than other tacrolimus based immunosuppressants. CONCLUSIONS: Although
      our study was based on a low risk population and had a shortterm follow up, we
      conclude that tacrobell, as a generic tacrolimus, can be considered safe and
      effective in liver transplant patients.

PMID- 21940372
TI  - Endoscopic submucosal dissection with sheath-assisted counter traction using a
      novel sheath for early gastric cancers.
AB  - BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) is technically demanding
      and requires considerable skill. We previously described sheath-assisted counter
      traction ESD that uses simple materials and methods to improve cutting line
      visualization. We recently improved counter-traction of the submucosal layer
      using a novel chemically treated sheath that reduces slippage and maintains
      traction, and investigated the utility of the novel sheath for ESD. METHODOLOGY:
      Forty-three and 25 consecutive patients with early gastric carcinomas were
      treated by standard ESD and traction ESD assisted with novel sheaths,
      respectively. The mean duration of procedures relative to tumor size and
      location, as well as complications after ESD between the two groups were
      compared. RESULTS: The mean duration of ESD procedures for lesions =20mm in
      diameter was significantly reduced using the novel sheath. The mean duration of
      procedures for all locations of resected tumors in the stomach was significantly
      reduced using the novel sheath. However, no perforation and delayed bleeding
      developed after treatment with the novel sheath. CONCLUSIONS: Sheath-assisted
      counter traction ESD by the novel sheath was technically simpler and thus less
      time-consuming regardless of the location of lesions, especially when =20mm in
      diameter. The traction ESD with the novel sheath is safe and not invasive, and it
      can be universally applied to standard ESD.

PMID- 21940373
TI  - Is endoscopic resection an acceptable treatment for undifferentiated EGC?
AB  - BACKGROUND/AIMS: Endoscopic resection (ER) is an effective treatment in selected
      patients with early gastric cancer (EGC). We have evaluated the clinical outcomes
      of ER in patients with undifferentiated EGCs, including poorly differentiated
      adenocarcinoma or signet ring cell carcinoma. METHODOLOGY: We retrospectively
      examined the medical records of 77 patients diagnosed with undifferentiated EGC
      after ER (EMR for 22 patients and ESD for 56 patients) at a single center.
      RESULTS: The mean+/-SD lesion size was 23.2+/-14.1mm. The 77 lesions included 65
      (84.4%) intramucosal cancers and 12 (15.6%) involving the submucosal layer. Of
      these 77 patients, 35 underwent curative resection and 42 did not. After a mean
      follow-up period of 41 months (range, 9-152), local recurrences were observed in
      four patients (5.2%), all of whom had not undergone curative resection. No
      patient died of EGC. Univariate analysis showed that tumor involvement of the
      resection margins (p<0.001) and lymphatic invasion (p=0.003) were significant
      risk factors for recurrence after ER in undifferentiated EGCs. However,
      multivariate analysis did not show any significant risk factors. CONCLUSIONS: ER
      may be an alternative treatment modality for selected patients with
      undifferentiated EGCs.

PMID- 21940374
TI  - Preventive effect of omental flap in pancreaticoduodenectomy against
      postoperative pseudoaneurysm formation.
AB  - BACKGROUND/AIMS: An omental flap covering the splanchnic vessels might reduce
      postoperative intraabdominal hemorrhage after pancreaticoduodenectomy. However,
      the efficiency of such a procedure remains to be verified. The purpose of this
      study was to determine the effect of omental flap placement in
      pancreaticoduodenectomy on the incidence of postoperative pseudoaneurysms.
      METHODOLOGY: Of 229 consecutive patients who underwent pancreaticoduodenectomy,
      the most recent 157 patients received the omental flap, while the initial 72
      patients had no omental flap placement. Various preoperative factors were
      considered in the evaluation (age, gender, body mass index, primary disease and
      concurrent disease), as well as operative factors (operation time, blood loss,
      operative procedures, pancreatic texture, size of pancreatic duct and surgeon's
      experience). RESULTS: Eighty-one patients (35.4%) developed pancreatic fistula.
      Nine patients (3.9%) developed postoperative pseudoaneurysm. Among the patients
      with pancreatic fistula, those without omental flap developed pseudoaneurysms
      more frequently (21.7%) than those with omental flap placement (5.2%).
      Multivariate analysis identified pancreatic fistula, no use of omental flap and
      hypertension, in that order, as predisposing factors for a pseudoaneurysm. The
      omental flap significantly prevented pseudoaneurysms (p=0.021; OR=0.151; 95% CI,
      0.030-0.751). CONCLUSIONS: Omental flap placement over splanchnic vessels could
      be a feasible and efficient surgical procedure to prevent postoperative
      pseudoaneurysms following pancreaticoduodenectomy.

PMID- 21940375
TI  - Pancreatic injury in children: review of 7 cases and the pertinent literature.
AB  - BACKGROUND/AIMS: Treatment of blunt injury of the pancreas in children remains
      controversial. Some prefer non-surgical treatment, whereas others prefer surgical
      management in selected cases. This report reviews our management strategies of
      children with blunt pancreatic trauma and their outcomes. METHODOLOGY: Medical
      records of 7 children with traumatic pancreatic injury were retrospectively
      analyzed in our institutions. In addition, we reviewed the pertinent literature.
      RESULTS: There were 2 males and 5 females with a median age of 7.6 years.
      Pancreatic injury was classified in 3 patients as grade I, in 2 patients as grade
      II, and in 2 patients as grade III (AAST). The two grade III children underwent
      ERCP preoperatively. ERCP showed injury to the main pancreatic duct in both of
      these patients, and emergency surgery was performed for both of them. These
      operative methods were spleen-preserving distal pancreatectomy and only drainage
      at the margin of the pancreas with non-resection, respectively. All 7 cases
      survived. CONCLUSIONS: ERCP is helpful for the diagnosis of suspected cases in
      pancreatic injury with grade III. In hemorrhagic shock state, appropriate
      surgical procedures with only drainage at the margin of the pancreas are useful
      for the treatment of pancreatic fistula in children.

PMID- 21940376
TI  - Contrast-enhanced ultrasonography in the diagnosis of gallbladder disease.
AB  - BACKGROUND/AIMS: The aim of our study was to evaluate the enhancement patterns of
      gallbladder disease using contrast-enhanced ultrasonography (CE-US) with the
      contrast agent levovist. METHODOLOGY: The subjects were 42 patients, of whom 25
      had gallbladder cancer, 2 had adenoma, 5 had adenomyomatosis, 5 had cholesterol
      polyps and 5 had debris. We assessed the enhancement patterns of each case using
      CE-US with levovist and classified these patterns into 6 types: diffuse,
      scattered, branched, linear, homogeneous and unenhanced. RESULTS: The enhancement
      of gallbladder cancer revealed various patterns. Only 4 malignant cases showed
      branched patterns. We speculated that branched patterns in the present study were
      possibly the characteristic of malignancy. CE-US easily distinguished a small
      polypoid lesion from debris. Using CE-US, we visualized the shape of the
      gallbladder cancer lesions and some areas of direct invasion to the liver, as
      well as metastasis. CONCLUSIONS: CE-US is a minimally invasive diagnostic
      technique that is useful in visualizing not only the shape of the lesion and some
      areas of the direct invasion to the liver, but also metastasis. The above
      findings suggest that imaging using a contrast agent could lead to improvements
      in the diagnosis of gallbladder lesions.

PMID- 21940377
TI  - Feasibility of snare papillectomy in ampulla of Vater tumors: meta-analysis and
      study results from a tertiary referral center.
AB  - BACKGROUND/AIMS: Ampulla of Vater tumors represent a rare tumor entity and bear a
      malignant potential. This study at our tertiary referral center aimed at
      evaluating the feasibility of endoscopic snare papillectomy and long-term
      endoscopic surveillance in comparison to results of a meta-analysis of
      comparative trials. METHODOLOGY: Retrospective study in comparison to results of
      a meta-analysis. Twenty-one patients (mean age 60.2+/-12.8 years) with ampullary
      adenoma were included. All patients had undergone ERCP with endoscopic forceps
      biopsies prior to endoscopic snare papillectomy. Statistical analysis was applied
      including descriptive analysis of symptoms, therapy and complications. RESULTS:
      ESP was technically successful in all 21 patients. Histopathology showed 18
      adenomas and 3 focal adenocarcinomas which were referred to surgery for modified
      Whipple's procedure. Follow-up was available in all patients with a mean follow
      up of 64 months. Adenoma recurrence occurred in three patients with a mean
      recurrence time of 25 months (range, 4-66 months). One patient had residual
      adenoma growth. CONCLUSIONS: In the majority of cases ampullary adenomas can be
      treated endoscopically. Forceps biopsies alone are not reliable enough in
      detecting malignancy. All patients with ampullary tumor should therefore undergo
      ESP. Due to the recurrence rate of 16% patients should have close follow-up.

PMID- 21940378
TI  - Effect of selective inflow occlusion on hemodynamic conditions during
      laparoscopic left hemihepatectomy effect of selective inflow occlusion on
      hemodynamic conditions during laparoscopic left hemihepatectomy.
AB  - BACKGROUND/AIMS: Selective inflow occlusion instead of portal triad clamping was
      used during laparoscopic left hemihepatectomy in our institution. This study
      observed its hemodynamic effects during operation. METHODOLOGY: Hemodynamic
      parameters including heart rate (HR), mean arterial pressure (MAP), central
      venous pressure (CVP), mean pulmonary artery pressure (PAP), pulmonary capillary
      wedge pressure (PCWP), cardiac index (CI), systemic vascular resistance (SVR) and
      pulmonary vascular resistance (PVR) were collected at 6 time points: after
      induction, after insufflation with CO2, after patient in reverse Trendelenburg
      position, after left branch of hepatic artery was occluded, after left branch of
      portal vein was occluded and after desufflation with patient supine. RESULTS: No
      severe perioperative cardiopulmonary complications were observed. Occlusion of
      left branch of hepatic artery brought no significant hemodynamic change.
      Occlusion of left branch of portal vein increased CVP and CI and decreased SVR.
      CO2 inflation caused HR, MAP and SVR to increase. The change to reverse
      Trendelenburg position caused CVP and PAP to decrease. When placed in the supine
      position with deflation, MAP, CVP, PAP, PCWP and CI went to a higher than base
      level. HR and SVR returned to base level. CONCLUSIONS: Using selective inflow
      occlusion in laparoscopic left hemihepatectomy caused few hemodynamic changes
      before and after occlusion in patients without cardiopulmonary diseases. However,
      the change of position and inflation or deflation caused significant changes.

PMID- 21940379
TI  - Causes of mortality after liver transplantation: a single center experience in
      mainland china.
AB  - BACKGROUND/AIMS: To analyze the causes of death, both in the short- and long-term
      after cadaveric liver transplantation (LT) from a single center in mainland
      China. METHODOLOGY: Clinical data of 472 adult patients who underwent primary
      cadaveric LT from February 1999 to December 2009 at our center were identified.
      All patients were followed-up until December 2010. Mortalities in three periods
      were described: the postoperative mortality (within the first 90 postoperative
      days or more if the patient remained hospitalized); the early mortality (death
      between 4-12 months after transplantation); the late mortality (death after one
      year following transplantation). RESULTS: The survival of the 472 patients at 3
      months, 1, 3 and 5 years was 85.2%, 73.5%, 61.2% and 59.7%, respectively. The
      postoperative mortality, the early mortality and the late mortality were 34.8%
      (70/201), 27.4% (55/201) and 37.8% (76/201), respectively. Infection, multi-organ
      failure and technical complications were the major causes of death during the
      first period, and the recurrence of malignancy was the main cause of death during
      the early and late periods after LT. CONCLUSIONS: Recurrence of malignancy was
      the major cause of the early and late mortality in our study, which is higher
      than that of other reports. The serious preoperative condition of the recipient,
      the waiting timing for the operation and the tumor selection criteria for LT may
      account for this.

PMID- 21940380
TI  - New candidate tumor-suppressor gene KLF6 and its splice variant KLF6 SV2
      counterbalancing expression in primary hepatocarcinoma.
AB  - BACKGROUND/AIMS: This study aimed to detect the expression of newly discovered
      zinc finger transcriptional factor KLF6 and its splice variant KLF6 SV2 in
      primary hepatocarcinoma (PHC) tissues and hepatoma cell strains, and to evaluate
      their clinicopathologic relationship with PHC. METHODOLOGY: Wild-type KLF6 and
      KLF6 SV2 mRNA expression was determined by RTPCR in 27 cases of PHC tissues and
      cell strains of HepG2, SMMC7721 and LO2. Western blotting and immunohistochemical
      staining were adopted to detect KLF6 protein expression. Positive area ratio of
      wild-type KLF6 protein expression and its relationship with clinicopathological
      parameters of PHC was analyzed. RESULTS: Wild-type KLF6 expression in PHC tissues
      was lower than that in paracancerous tissues. In contrast, KLF6 SV2 mRNA
      expression was higher in PHC tissues and hepatoma cell strains (p<0.05). Positive
      area ratio of wild-type KLF6 protein expression was positively correlated with
      cellular differentiation degree of PHC (p<0.01), but negatively correlated not
      only with liver cirrhosis, tumor size and extrahepatic metastases (p<0.01), but
      also with portal vein thrombus and the number of lymph nodes with metastasis
      (p<0.05). CONCLUSIONS: Wild-type KLF6 deletion and inactivation was involved in
      the growth, cell differentiation and other physiological processes of PHC. The
      upregulation of KLF6 splice variant might counterbalance the wildtype KLF6 and
      contribute to the occurrence and development of PHC.

PMID- 21940381
TI  - The amelioration of AH by abstinence and the attenuation of oxidative stress.
AB  - BACKGROUND/AIMS: Alcohol abstinence is considered the cornerstone in the
      management of alcoholic hepatitis (AH), but the degree of improvement and how
      abstinence ameliorates alcoholic liver injury remains unclear. The purpose of the
      study was to investigate the amelioration of AH after 3 and 6 months of alcohol
      abstinence, and its possible mechanism. METHODOLOGY: Thirty-six AH patients who
      strictly abstained from alcohol and 20 AH patients who did not abstain from
      alcohol, were followed-up for 6 months. The control group consisted of 15 healthy
      individuals with no history of alcohol abuse. The testing of serum biomarkers and
      abdominal CT scans were performed. RESULTS: Alcohol abstinence ameliorated the AH
      by decreasing the liver enzyme and fibrotic markers, and improving the hepatic
      steatosis. Comparing between AH patients with and without alcohol abstinence, the
      ratio between hepatic and splenic CT value were 1.01 +/- 0.13 and 0.75 +/- 0.25,
      respectively (p<0.01). GSH and SOD levels were significantly higher, while the
      MDA level was significantly lower, in patients with abstinence compared to those
      without abstinence. CONCLUSIONS: Alcohol abstinence is useful in the clinical
      management of AH. The attenuation of AH was associated with the decrease of
      oxidative stress.

PMID- 21940382
TI  - A non-randomized comparative study of laparoscopy-assisted
      pancreaticoduodenectomy and open pancreaticoduodenectomy.
AB  - BACKGROUND/AIMS: Laparoscopic surgery for periampullary disease is still a
      challenging operation. The aim of this study was to compare the perioperative
      outcomes of patients undergoing conventional pancreaticoduodenectomy (PD) with
      the outcomes of those undergoing laparoscopy-assisted PD. METHODOLOGY: A
      retrospective analysis was conducted on 51 consecutive patients who underwent
      laparoscopy-assisted or open PD for periampullary disease. RESULTS: There were no
      significant differences in the preoperative demographic or clinical data of the
      two study groups. Although there were no significant differences in the operative
      time between the two study groups, blood loss in the laparoscopy-assisted PD
      group was significantly smaller than that in the open PD group. There were no
      significant differences in the occurrence of postoperative complications between
      the two groups. CONCLUSIONS: Laparoscopy-assisted PD is a feasible and safe
      surgical procedure that provides the advantages expected from a minimally
      invasive surgery including less blood loss.

PMID- 21940383
TI  - Comparison of the efficacy of entecavir and tenofovir in chronic hepatitis B.
AB  - BACKGROUND/AIMS: This study aimed to compare the efficacy of entecavir and
      tenofovir in nucleos(t)ide-naive chronic hepatitis B patients after 48 weeks of
      therapy. METHODOLOGY: We retrospectively reviewed our data of chronic hepatitis B
      patients. Nucleos(t)ide-naive patients who had received entecavir or tenofovir
      for at least 48 weeks were included. We compared entecavir and tenofovir after 48
      weeks of therapy with respect to virological, biochemical, serological and
      histological responses. RESULTS: Of the 44 patients, 24 received entecavir and 20
      received tenofovir. Pretreatment characteristics of the patients were similar.
      After 48 weeks, serum HBV DNA levels decreased by 6.93+/-1.54log copy/ mL in the
      entecavir group and 6.89+/-1.22log copy/mL in the tenofovir group (p=0.65). A
      similar proportion of patients in entecavir and tenofovir groups achieved
      undetectable serum HBV DNA (87.5% vs. 95%, p=0.39) and serum ALT normalization
      (79.2% vs. 85%, p=0.62). The mean histological activity index score improved by
      3.83+/-3.51 points in the entecavir group and 2.20+/-1.91 points in the tenofovir
      group (p=0.07), and the mean fibrosis scores improved by 0.38+/-1.61 points in
      the entecavir group and 0.70+/-1.17 points in the tenofovir group after 48 weeks
      (p=0.44). CONCLUSIONS: Entecavir and tenofovir are similarly effective in
      nucleos(t)ide-naive chronic hepatitis B patients with high viral load and/or high
      fibrosis scores after 48 weeks of therapy.

PMID- 21940384
TI  - Practical usefulness of minor grooves of the hepatic surface for liver resection.
AB  - BACKGROUND/AIMS: The clinical relevance of grooves of the hepatic surface has not
      been clearly identified. The aim of the present study was to examine the
      association of minor grooves and liver segmentations, and to evaluate the
      usefulness of grooves for liver resection. METHODOLOGY: Between January 2005 and
      December 2010, 482 patients with hepatic resection for liver disease were
      included in this study. We performed glissonean pedicle transection methods for
      hepatic resection to identify sectors or segments of the liver and examined
      location, size, depth and relationship with intersegmental line of the hepatic
      grooves. RESULTS: Diaphragmatic grooves were located on anatomical border between
      right lobe and left lobe and within right anterior sector. The minor grooves were
      more commonly observed in the right lobe than in the left lobe. The minor grooves
      between segment V and VI, and segment V and VI were easy to perform
      monosegmentectomy and right anterior sectionectomy on, respectively. These minor
      grooves were also helpful to determine the resection margin for non-anatomical
      resection. CONCLUSIONS: Minor grooves were often observed in line with sector or
      segment, or near to inter-segmental or sectorial border. The anatomical knowledge
      of hepatic grooves including minor type may be of help for hepatobiliary surgeons
      and radiologists to understand liver segmentation.

PMID- 21940385
TI  - Long-term follow-up of central hepatocellular carcinoma in comparison with non
      central hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Multiple hepatic vessels and portal vessels are distributed in
      the central segments of the liver (segments IV, V and VIII). Due to its
      anatomical complexity, in centrally-located hepatocellular carcinoma (cHCC) it is
      theoretically not easy to reach a wide margin, as it is in non-central
      hepatocellular carcinoma (ncHCC) (segments II, III, VII and VIII). We compared
      their outcomes to see if cHCC has an inferior result than ncHCC. METHODOLOGY:
      From August 2000 to July 2008, 213 HCC patients received curative-intended
      resection. Sixty-nine cHCC (group A) and 64 ncHCC (group B) received
      trisegmentectomy (include mesohepatectomy), bi-segmentectomy, mono-segmentectomy
      or subsegmentectomy. The outcomes were retrospectively analyzed. RESULTS: The in
      hospital mortality was 0% and 3.12% in groups A and B, respectively (p=0.55). The
      morbidity was 27.5% and 28.1% in groups A and B, respectively (p=0.23). The 1-
      and 3-year disease-free survival were 68%, 50% and 62%, 33% in groups A and B,
      respectively (p=0.39). The 1- and 3-year overall survival rates were 83%, 75% and
      89%, 70% in groups A and B, respectively (p=0.91). Tumor size and numbers were
      significant factors for disease-free and overall survival. CONCLUSIONS: cHCC
      treated by partial hepatectomy and mesohepatectomy has a comparable result to
      ncHCC. Mesohepatectomy is needed only in some selected patients.

PMID- 21940386
TI  - Association of family history of HBV with resectability of hepatocellular
      carcinoma.
AB  - BACKGROUND/AIMS: This study aims to address the relationship between a positive
      family history of liver cancer or hepatitis B virus (HBV) infection and the
      operative resectability of hepatocellular carcinoma (HCC) in the Chinese
      population. METHODOLOGY: Two hundred and sixty-two HCC patients underwent
      operative or non-operative therapies in our hospital. One hundred and eighteen of
      the patients were clinically considered as resectable patients. The remaining 144
      patients were clinically unresectable. Statistical analysis was performed in SPSS
      15.0 for Windows. RESULTS: A family history of HBV infection is significantly
      associated with the resectability of HCC (AOR=2.332; 95% CI, 1.051-5.177). There
      was also has a significant association between the first degree relatives
      infected with HBV and the resectability of HCC (AOR=2.334; 95% CI, 1.050-5.190),
      especially a patient's sibling having a history of HBV infection is significantly
      related to the resectability of HCC (AOR=2.727; 95% CI, 1.092-6.808).
      CONCLUSIONS: A family history of HBV infection is associated with the
      resectability of HCC, and in particular, if a patient's sibling has a history of
      HBV infection, this indicates a reduced opportunity to receive curative liver
      resection.

PMID- 21940387
TI  - Antithrombin prevents apoptosis by regulating inflammation in the liver in a
      model of cold ischemia/warm reperfusion injury.
AB  - BACKGROUND/AIMS: Hepatic ischemia-reperfusion injury is a major problem in liver
      surgery. To modulate the complex process of inflammation, additional drugs to add
      to well-defined organ preserving solutions have been sought. The aim of the
      current study was to investigate the additive potential of antithrombin (AT) in
      liver preservation. METHODOLOGY: Female Wistar rats were randomized into four
      groups: sham (Group I), experiment model (Group II), and treatment groups with AT
      (250U/kg) administration systematically (Group III) or locally (Group IV) before
      hepatectomy. UW solution was used for liver preservation for 24h at 4 degrees C.
      The livers in group II, III and IV were reperfused 1h and histopathological
      parameters were evaluated microscopically. Apoptosis was assessed with TUNEL
      test. RESULTS: Karyorrhexis was lower in the local treatment with AT group.
      Sinusoidal desquamation and mononuclear cell infiltration was higher in the
      experimental model group. Sinusoidal enlargement was higher in the systemic AT
      treatment group and neutrophil infiltration to sinusoids was lowest in the local
      treatment group. Apoptosis of hepatocytes and sinusoidal cells were significantly
      suppressed in rats that were treated with AT via portal vein infusion.
      CONCLUSIONS: AT treatment obviously contributed to liver preservation in our
      model; the effects on apoptosis and inflammation were prominent. Therefore, AT
      should be considered as a potent agent although its clinical role has yet to be
      defined in ex-vivo hepatic preservation.

PMID- 21940388
TI  - Telaprevir for chronic hepatitis C with genotype 1: a meta-analysis.
AB  - BACKGROUND/AIMS: The examination of HCV virological clearance through several
      randomized clinical trials of telaprevir in genotype 1 chronic hepatitis C.
      METHODOLOGY: We analyzed the effect of telaprevir on the end of treatment
      virological response and the sustained response, and investigated its harmful
      effect using meta-analysis of 5 randomized controlled trials. RESULTS: Overall
      analysis revealed a significant effect of telaprevir in both naive patients (RR,
      1.32; 95% CI, 1.08-1.60) and previously failed treated patients (p<0.0001).
      Monotherapy and double therapy seemed to show no effect in naive patients. Triple
      therapy followed with PegIFN-2a plus ribavirin seemed to be effective in both
      naive patients and previously failed treated patients. Telaprevir was associated
      with a significantly higher incidence of serious adverse events (RR, 1.45; 95%
      CI, 1.00-2.10) and with discontinuation (RR, 2.23; 95% CI, 1.40-3.55) because of
      adverse events. In naive patients, relapsers and non-responders, the regimen of
      telaprevir/ PegIFN-2a/ribavirin for 12 weeks followed by PegIFN-2a/ribavirin for
      12 weeks (T12PR24) was the optimal regimen regarding to efficiency and duration.
      CONCLUSIONS: Telaprevir combined with PegIFN-2a plus ribavirin may improve
      sustained response in genotype 1 chronic hepatitis C. Regimen T12PR24 may be the
      best regimen in this respect. New randomized controlled trials are required to
      confirm this meta-analysis.

PMID- 21940389
TI  - Safety of patients with a graft to body weight ratio less than 0.8% in living
      donor liver transplantation using right hepatic lobe without middle hepatic vein.
AB  - BACKGROUND/AIMS: This study aimed to evaluate the postoperative outcomes of
      patient with a graft with graft to body weight ratio (GBWR) less than 0.8% after
      living donor liver transplantation (LDLT) using the right hepatic lobe without
      middle hepatic vein (MHV). METHODOLOGY: The clinical data of patients who
      underwent LDLTs using the right hepatic lobe without the MHV, between March 2006
      and April 2009, were retrospectively analyzed. Patients were divided into two
      groups according to the GBWR (group A, GBWR <0.8%; group B, GBWR =0.8%).
      Preoperative characteristics were statistically analyzed. Postoperative
      complications were classified by the Clavien classification. The Kaplan-Meier
      survival analysis with logrank test was used to compare the long-term survival of
      two groups. RESULTS: The two groups were comparable. Similar incidence of serious
      postoperative surgical complication (grade =3) was observed between the two
      groups. The 1-, 3- and 4-year survival rates of the two groups were 81%, 64% and
      57%, and 83%, 71% and 64%, respectively. No significant differences were
      observed. CONCLUSIONS: Small-forsize graft (GBWR <0.8%) can be safely used in
      adult to- adult LDLT using right hepatic lobe without MHV.

PMID- 21940390
TI  - A new non-invasive modality for recording sequential images and the pH of the
      small bowel.
AB  - BACKGROUND/AIMS: Before the introduction of capsule endoscopy and double-balloon
      endoscopy, there were no effective modalities for reliable evaluation of the
      small bowel. Recently, the SmartPill, a wireless pH/ pressure recording capsule,
      has been utilized to measure the whole gut transit time. However, there are few
      studies on the small bowel pH. The aim of this study was to investigate the
      relationship between small bowel disease and the small bowel pH, we designed a
      new modality, the 'pH capsule', to non-invasively record sequential images and
      the pH. METHODOLOGY: Ten healthy male volunteers swallowed the 'pH capsule' with
      50mL of water. The 'pH capsule' transmitted the acquired images and the pH to the
      recorder unit located outside the body for about ten hours while the subject was
      fasting. RESULTS: All subjects completed this study. The intragastric pH was low
      and the pH in the whole small intestine was 7.61, 7.55: 7.2-8.1 (mean, median:
      range). The pH value increased from the duodenum to the terminal ileum
      (p<0.0001). CONCLUSIONS: We could non-invasively monitor sequential images and
      the pH of the small intestine with this new modality. The 'pH capsule' is
      expected to become a valuable tool for clinical assessment of the small bowel.

PMID- 21940391
TI  - Evaluation of remnant liver function using 13C-breath tests in a rat model of 70%
      partial hepatectomy.
AB  - BACKGROUND/AIMS: A 13C breath test was applied to evaluate the early stage of
      postoperative liver function after hepatectomy. It was examined in comparison
      with functional and morphological recovery. METHODOLOGY: Rats were subjected to
      70% partial hepatectomy (H group) and control group (S group). Expired air, blood
      and remnant liver tissue were collected at 12, 24, 48 and 72h, and 7 and 14 days
      postoperatively. Phenylalanine and leucine were used as the 13C-labeled
      substrates. The 13CO2 was collected until 120min. The mean values of the H and S
      groups were compared using the highest mean level of 13CO2 excreted in breath
      (Cmax). The liver regenerative ability was evaluated by Ki-67. RESULTS: In the
      13C-phenylalanine breath test, the Cmax value tended to be lower for the H group
      12h postoperatively (p=0.06). Cmax was significantly lower for the H group 24h
      postoperatively (p<0.05). Both groups showed equal recovery at 48h
      postoperatively. In the 13C-leucine breath test, both groups had no significant
      difference after hepatectomy. The peak of Ki-67 positive rate is estimated to be
      at 52.8h postoperatively, meaning that the time difference was only approximately
      5h between the peak time of Ki-67 positive rate and the 13C-phenylalanine breath
      test. CONCLUSIONS: These results strongly support that the 13C-phenylalanine
      breath test can become a non-invasive indicator to evaluate the early stage of
      postoperative liver function after hepatectomy.

PMID- 21940392
TI  - Enhanced lymph node retrieval from colorectal cancer resections using a simple
      lymphatic staining method.
AB  - BACKGROUND/AIMS: This study evaluated the effect of lymphatic staining on the
      number of lymph nodes (LNs) examined and staging in patients with colorectal
      cancer. METHODOLOGY: Sixty-two consecutive specimens from patients with
      colorectal cancer resected between February 2009 and April 2010 were randomized
      to the stained group or the control unstained. Differences in the retrieval,
      number and size of nodes, and time for retrieval were measured. RESULTS: LN
      harvest differed significantly with 30+/-12 and 13+/-5 (p<0.01) nodes in the
      stained and the control groups, respectively. Insufficient LN harvest (less than
      12 nodes) occurred in 14 cases of the control group and only in 1 case of the
      stained group (p<0.01). Metastases were confirmed in 57 LNs occurring in 17 cases
      of the stained group and in 39 nodes occurring in 15 cases of the control group.
      The mean time for LN retrieval in the stained and control groups were comparable,
      27.6+/-6.9min and 24.7+/-6.0min (p>0.05), respectively, yet there was a
      significant difference in the number of LNs (<2mm) (294 vs. 59, respectively,
      p<0.01) as well as in the number of LNs 2-5mm in size (474 vs. 220, respectively,
      p<0.01). CONCLUSIONS: By lymphatic staining method, more and smaller LNs could be
      detected, which significantly improved the LN harvest of resected colorectal
      specimens and reduced cases of insufficient LN harvest.

PMID- 21940393
TI  - Single-incision laparoscopic cholecystectomy with needle graspers.
AB  - BACKGROUND/AIMS: Single-incision laparoscopic cholecystectomy (SILC) is a
      promising alternative to standard multi-incision laparoscopic cholecystectomy
      (LC). However, generalization of SILC is still hampered by technical difficulties
      mainly associated with the lack of trocars used for retraction of the
      gallbladder. We therefore developed a modified method of SILC with the use of
      needle graspers (SILC-N) for optimal retraction and exposure. METHODOLOGY: In
      addition to two trocars inserted through a single transumbilical incision, two
      needle ports were placed on the right subcostal and lateral abdominal wall,
      through which needle graspers were used for retraction of the gallbladder. Since
      December, 2009, 12 patients with symptomatic cholelithiasis were treated by SILC
      N. RESULTS: SILC-N was successfully performed in all but one patient requiring a
      conversion to the 4-port LC with a mean operative time of 71.5 (48-107) minutes.
      None of the patients experienced intraoperative or postoperative complications.
      The transumbilical incision and pinholes for needle graspers were almost
      invisible on discharge. CONCLUSIONS: Our preliminary results suggest that SILC-N
      is a simple, safe and feasible technique of cholecystectomy offering similar
      postoperative recovery and better cosmetic outcome as compared to conventional
      LC.

PMID- 21940394
TI  - Evaluation of correct endogenous reactive oxygen species content for human sperm
      capacitation and involvement of the NADPH oxidase system.
AB  - BACKGROUND: Generation of controlled amounts of reactive oxygen species (ROS) and
      phosphorylation of protein tyrosine residues (Tyr) are two closely related
      changes involved in sperm capacitation. This study investigated the effect of
      altered endogenous ROS production on Tyr-phosphorylation (Tyr-P), acrosome
      reaction (AR) and cell viability during sperm capacitation. The possible origin
      of the altered ROS production was also evaluated by apocynin (APO) or oligomycin
      (Oligo) addition. METHODS: A total of 63 samples of purified sperm were analysed
      for ROS production by enhanced chemiluminescence, Tyr-P pattern by
      immunocytochemistry, and AR and viability by fluorochrome fluorescein
      isothiocyanate (FITC)-labelled peanut (Arachis hypogaea) agglutinin and propidium
      iodide positivity, respectively. RESULTS: Samples were divided into four
      categories depending on the ability of sperm to produce ROS, expressed as
      Relative Luminescence Units (RLU), in capacitating conditions: low ROS production
      (LRP), range about 0.0-0.05 RLU; normal (NRP), 0.05-0.1 RLU; high (HRP), 0.1-0.4
      RLU; very high (VHRP) 0.4-2.0 RLU. In NRP sperm heads, capacitation induced Tyr-P
      in 87.9 +/- 4.3%, and the AR occurred in 62.5 +/- 5.4% of cells; in LRP, HRP and
      VHRP Tyr-P labelling rarely spread over the head, acrosome-reacted cells only
      accounted for a small number of sperm, and the non-viable cells (NVC) were
      increased. The addition of APO, but not Oligo, drastically decreased ROS
      production in analysed samples. CONCLUSIONS: This study proposes the optimal
      threshold for endogenous ROS production for correct sperm viability and
      functioning, and indicates the direct involvement of APO-sensitive NADPH oxidase
      in ROS production.

PMID- 21940395
TI  - Retention and extinction of delay eyeblink conditioning are modulated by central
      cannabinoids.
AB  - Rats administered the cannabinoid agonist WIN55,212-2 or the antagonist SR141716A
      exhibit marked deficits during acquisition of delay eyeblink conditioning, as
      noted by Steinmetz and Freeman in an earlier study. However, the effects of these
      drugs on retention and extinction of eyeblink conditioning have not been
      assessed. The present study examined the effects of WIN55,212-2 and SR141716A on
      retention and extinction of delay eyeblink conditioning in rats. Rats were given
      acquisition training for five daily sessions followed by one session of retention
      training with subcutaneous administration of 3 mg/kg of WIN55,212-2 or 5 mg/kg of
      SR141716A and an additional session with the vehicle. Two sessions of extinction
      training were then given with WIN55,212-2, SR141716A, or vehicle. Retention and
      extinction were impaired by WIN55,212-2, whereas SR141716A produced no deficits.
      The extinction deficit in rats given WIN55,212-2 was observed only during the
      first session, suggesting a specific impairment in short-term plasticity
      mechanisms. The current results and previous findings indicate that the
      cannabinoid system modulates cerebellar contributions to acquisition, retention,
      and extinction of eyeblink conditioning.

PMID- 21940396
TI  - Early detection of postoperative acute kidney injury by Doppler renal resistive
      index in cardiac surgery with cardiopulmonary bypass.
AB  - BACKGROUND: Acute kidney injury (AKI) is common after cardiac surgery, affecting
      outcome. Early detection of an AKI marker is likely to speed diagnosis and
      implementation of measures to preserve renal function. In septic shock and
      unselected ventilated subjects, an increased Doppler renal resistive index (RRI)
      is a predictor of AKI. This study aims to determine whether RRI would act
      similarly in the postoperative setting of cardiac surgery. METHODS: This study
      included 65 subjects aged more than 60 yr undergoing elective heart surgery with
      cardiopulmonary bypass (CPB) and at risk of AKI. All presented at least one AKI
      risk factor [arteritis, diabetes, or serum creatinine (sCr) clearance of 30-60 ml
      min(-1)] and were haemodynamically stable without arrhythmia. Doppler RRI was
      measured in the immediate postoperative period (POP) while subjects were
      ventilated and sedated. AKI was assessed when sCr increased 30% above the
      preoperative baseline. RESULTS: Eighteen subjects developed AKI between days 1
      and 4, with six requiring dialysis. RRI in the POP was increased in AKI [RRI:
      0.79 (0.08) with AKI vs 0.68 (0.06) without AKI, P<0.001], correlating to AKI
      severity [0.68 (0.06) without AKI, 0.77 (0.08) with AKI but no dialysis, and 0.84
      (0.03) with AKI and dialysis, P<0.001]. RRI was similar in subjects receiving
      catecholamines. RRI >0.74 in the POP predicted delayed AKI with high sensitivity
      and specificity (0.85 and 0.94, respectively). Multivariate analysis showed that
      AKI was associated with increased RRI and transfusion. CONCLUSIONS: RRI used in
      the immediate POP after cardiac surgery with CPB enabled prediction of delayed
      AKI and anticipation of its severity.

PMID- 21940397
TI  - Randomized controlled trial of the A.P. Advance, McGrath, and Macintosh
      laryngoscopes in normal and difficult intubation scenarios: a manikin study.
AB  - BACKGROUND: Several videolaryngoscopes are available which may facilitate
      tracheal intubation in difficult airways. We compared the McGrath((r)) Series 5
      and the VennerTM A.P. AdvanceTM (APA) videolaryngoscopes with a Macintosh
      laryngoscope by studying the performance of experienced anaesthetists using
      manikins in normal and difficult airway scenarios. METHODS: We recruited 48
      anaesthetists into a randomized trial. Each performed tracheal intubation with
      each laryngoscope in one easy and one difficult laryngoscopy scenario. The
      primary endpoint was time to intubation. Other endpoints were time to best
      glottic visualization, grade of view, and number of glottic advances. RESULTS:
      There were no dropouts. In the easy scenario, the time to intubation was greater
      using the McGrath [median time 40.7 s, inter-quartile range (IQR) 31.0, 57.4,
      P<0.001] than the other devices. In the difficult scenario, the time to
      intubation using the APA with Difficult Airway Blade (DAB) was less (median time
      23.2 s, IQR 19.8, 29.0, P<0.001) than the other devices. Time to glottic
      visualization was reduced using the McGrath and the APA with DAB. Glottic
      advances were fewer using the APA with DAB. CONCLUSIONS: Experienced
      anaesthetists required a longer time for intubation in a standard manikin using a
      McGrath compared with other laryngoscopes, but a shorter time for intubation in a
      difficult manikin using an APA with DAB, and with fewer glottic advances,
      compared with other laryngoscopes.

PMID- 21940398
TI  - BitterDB: a database of bitter compounds.
AB  - Basic taste qualities like sour, salty, sweet, bitter and umami serve specific
      functions in identifying food components found in the diet of humans and animals,
      and are recognized by proteins in the oral cavity. Recognition of bitter taste
      and aversion to it are thought to protect the organism against the ingestion of
      poisonous food compounds, which are often bitter. Interestingly, bitter taste
      receptors are expressed not only in the mouth but also in extraoral tissues, such
      as the gastrointestinal tract, indicating that they may play a role in digestive
      and metabolic processes. BitterDB database, available at
      http://bitterdb.agri.huji.ac.il/bitterdb/, includes over 550 compounds that were
      reported to taste bitter to humans. The compounds can be searched by name,
      chemical structure, similarity to other bitter compounds, association with a
      particular human bitter taste receptor, and so on. The database also contains
      information on mutations in bitter taste receptors that were shown to influence
      receptor activation by bitter compounds. The aim of BitterDB is to facilitate
      studying the chemical features associated with bitterness. These studies may
      contribute to predicting bitterness of unknown compounds, predicting ligands for
      bitter receptors from different species and rational design of bitterness
      modulators.

PMID- 21940399
TI  - The human translation initiation multi-factor complex promotes methionyl-tRNAi
      binding to the 40S ribosomal subunit.
AB  - The delivery of Met-tRNA(i) to the 40S ribosomal subunit is thought to occur by
      way of a ternary complex (TC) comprising eIF2, GTP and Met-tRNA(i). We have
      generated from purified human proteins a stable multifactor complex (MFC)
      comprising eIF1, eIF2, eIF3 and eIF5, similar to the MFC reported in yeast and
      plants. A human MFC free of the ribosome also is detected in HeLa cells and
      rabbit reticulocytes, indicating that it exists in vivo. In vitro, the MFC-GTP
      binds Met-tRNA(i) and delivers the tRNA to the ribosome at the same rate as the
      TC. However, MFC-GDP shows a greatly reduced affinity to Met-tRNA(i) compared to
      that for eIF2-GDP, suggesting that MFC components may play a role in the release
      of eIF2-GDP from the ribosome following AUG recognition. Since an MFC-Met-tRNA(i)
      complex is detected in cell lysates, it may be responsible for Met-tRNA(i)-40S
      ribosome binding in vivo, possibly together with the TC. However, the MFC protein
      components also bind individually to 40S ribosomes, creating the possibility that
      Met-tRNA(i) might bind directly to such 40S-factor complexes. Thus, three
      distinct pathways for Met-tRNA(i) delivery to the 40S ribosomal subunit are
      identified, but which one predominates in vivo remains to be elucidated.

PMID- 21940400
TI  - A novel vascular EET synthase: role of CYP2C7.
AB  - We demonstrated previously that cytochrome P-450 (CYP) 2C29 is the
      epoxyeicosatrienoic acid (EET) synthase responsible for the EET-mediated
      flow/shear stress-induced dilation of vessels of female nitric oxide (NO)
      deficient mice (Sun D, Yang YM, Jiang H, Wu H, Ojami C, Kaley G, Huang A. Am J
      Physiol Regul Integr Comp Physiol 298: R862-R869, 2010). In the present study, we
      aimed to identify which specific CYP isoform(s) is the source of the synthesis
      and release of EETs in response to stimulation by shear stress in vessels of
      rats. Cannulated mesenteric arteries isolated from both sexes of N(G)-nitro-L
      arginine methyl ester (L-NAME)-treated rats were perfused with 2 and 10 dyn/cm(2)
      shear stress, followed by collection of the perfusate to determine EET
      concentrations and isoforms. Shear stress stimulated release of EETs in the
      perfusate of female (but not male) NO-deficient vessels, associated with an EET
      mediated vasodilation, in which 11,12- and 14,15-EET contributed predominantly to
      the responses. Rat CYP cDNA array screened a total of 32 CYP genes of mesenteric
      arteries, indicating a significant upregulation of CYP2C7 in female L-NAME
      treated rats. Endothelial RNA and protein were extracted from intact single
      vessels. Expression of CYP2C7 mRNA and protein in pooled extractions of
      endothelial lysate was identified by PCR and Western blot analyses. Transfection
      of the vessels with CYP2C7 short interfering RNA eliminated the release of EETs,
      consequently abolishing the EET-mediated flow-induced dilation; these responses,
      however, were maintained in vessels transfected with nonsilencing short
      interfering RNA. Knockdown of endothelial CYP2C7 was confirmed by PCR and Western
      blot analyses. In conclusion, CYP2C7 is an endothelial EET synthase in the female
      rat vasculature, by which, in NO deficiency, shear stress stimulates the release
      of EETs to initiate vasodilation.

PMID- 21940401
TI  - Acute and chronic effects of SGLT2 blockade on glomerular and tubular function in
      the early diabetic rat.
AB  - Tubuloglomerular feedback (TGF) stabilizes nephron function from minute to minute
      and adapts to different steady-state inputs to maintain this capability. Such
      adaptation inherently renders TGF less efficient at buffering long-term
      disturbances, but the magnitude of loss is unknown. We undertook the present
      study to measure the compromise between TGF and TGF adaptation in transition from
      acute to chronic decline in proximal reabsorption (Jprox). As a tool, we blocked
      proximal tubule sodium-glucose cotransport with the SGLT2 blocker dapagliflozin
      in hyperglycemic rats with early streptozotocin diabetes, a condition in which a
      large fraction of proximal fluid reabsorption owes to SGLT2. Dapagliflozin
      acutely reduced proximal reabsorption leading to a 70% increase in early distal
      chloride, a saturated TGF response, and a major reduction in single nephron
      glomerular filtration rate (SNGFR). Acute and chronic effects on Jprox were
      indistinguishable. Adaptations to 10-12 days of dapagiflozin included increased
      reabsorption by Henle's loop, which caused a partial relaxation in the increased
      tone exerted by TGF that could be explained without desensitization of TGF. In
      summary, TGF contributes to long-term fluid and salt balance by mediating a
      persistent decline in SNGFR as the kidney adapts to a sustained decrease in
      Jprox.

PMID- 21940402
TI  - Cannabinoid and GABA modulation of sympathetic nerve activity and blood pressure
      in the dorsal periaqueductal gray of the rat.
AB  - Sympathoexcitation and increased blood pressure evoked by central networks
      integrating defensive behavior are fundamental to the acute stress response. A
      balance between excitatory glutamatergic and inhibitory GABAergic
      neurotransmission in the dorsal periaqueductal gray (dPAG) results in a tonic
      level of activity in the alerting system. Neuromodulators such as
      endocannabinoids have been shown to influence the sympathoexcitatory and pressor
      components of acute stress in the dPAG, exemplified by the defense response as a
      model, but the mechanism of integration remains unknown. The present study
      examines the role of GABA and its interaction with endocannabinoids in modulating
      sympathetic nerve activity and blood pressure related to the defense response.
      Microinjection of the broad-spectrum excitatory amino acid dl-homocysteic acid
      (DLH) identified sites of the defense pathway in the dPAG from which an increase
      in renal sympathetic nerve activity and blood pressure could be evoked, and
      subsequent microinjections were made at the same site through a multibarrelled
      micropipette. Blockade of GABAA receptors or microinjection of the cannabinoid 1
      receptor agonist anandamide elicited a renal sympathoexcitation and pressor
      response. Prior microinjection of the GABAA receptor antagonist gabazine
      attenuated the sympathoexcitation and pressor response associated with anandamide
      microinjection. In contrast, the sympathetic response to DLH was enhanced by
      GABAA receptor blockade. These data demonstrate that sympathoexcitatory neurons
      in the dPAG are under tonic inhibition by GABA and that endocannabinoids modulate
      this GABAergic neurotransmission to help regulate components of the defense
      response.

PMID- 21940403
TI  - Mitochondrial superoxide and coenzyme Q in insulin-deficient rats: increased
      electron leak.
AB  - Mitochondrial superoxide is important in the pathogeneses of diabetes and its
      complications. However, there is uncertainty regarding the intrinsic propensity
      of mitochondria to generate this radical. Studies to date suggest that superoxide
      production by mitochondria of insulin-sensitive target tissues of insulin
      deficient rodents is reduced or unchanged. Moreover, little is known of the role
      of the Coenzyme Q (CoQ), whose semiquinone form reacts with molecular oxygen to
      generate superoxide. We measured reactive oxygen species (ROS) production,
      respiratory parameters, and CoQ content in mitochondria from gastrocnemius muscle
      of control and streptozotocin (STZ)-diabetic rats. CoQ content did not differ
      between mitochondria isolated from vehicle- or STZ-treated animals. CoQ also was
      unaffected by weight loss in the absence of diabetes (induced by caloric
      restriction). Under state 4 or state 3 conditions, both respiration and ROS
      release were reduced in diabetic mitochondria fueled with succinate, glutamate
      plus malate, or with all three substrates (continuous TCA cycle). However,
      H(2)O(2) and directly measured superoxide production were substantially increased
      in gastrocnemius mitochondria of diabetic rats when expressed per unit oxygen
      consumed. On the basis of substrate and inhibitor effects, the mechanism involved
      multiple electron transport sites. More limited results using heart mitochondria
      were similar. ROS per unit respiration was greater in muscle mitochondria from
      diabetic compared with control rats during state 3, as well as state 4, while the
      reduction in ROS per unit respiration on transition to state 3 was less for
      diabetic mitochondria. In summary, ROS production is, in fact, increased in
      mitochondria from insulin-deficient muscle when considered relative to electron
      transport. This is evident on multiple energy substrates and in different
      respiratory states. CoQ is not reduced in diabetic mitochondria or with weight
      loss due to food restriction. The implications of these findings are discussed.

PMID- 21940404
TI  - Sympathetic and cardiovascular responses to venous distension in an occluded
      limb.
AB  - We recently showed that a fixed volume (i.e., 40 ml) of saline infused into the
      venous circulation of an arterially occluded vascular bed increases muscle
      sympathetic nerve activity (MSNA) and blood pressure. In the present report, we
      hypothesized that the volume and rate of infusion would influence the magnitude
      of the sympathetic response. Blood pressure, heart rate, and MSNA were assessed
      in 13 young healthy subjects during forearm saline infusions (arrested
      circulation). The effects of different volumes of saline (i.e., 2%, 3%, 4%, or 5%
      forearm volume at 30 ml/min) and different rates of infusion (i.e., 5% forearm
      volume at 10, 20, or 30 ml/min) were evaluated. MSNA and blood pressure responses
      were linked with the infusion volume. Infusion of 5% of forearm volume evoked
      greater MSNA responses than did infusion of 2% of forearm volume (Delta11.6 +/-
      1.9 vs. Delta3.1 +/- 1.8 bursts/min and Delta332 +/- 105 vs. Delta38 +/- 32
      units/min, all P < 0.05). Moreover, greater MSNA responses were evoked by saline
      infusion at 30 ml/min than 10 ml/min (P < 0.05). Sonographic measurements
      confirmed that the saline infusions induced forearm venous distension. The
      results suggest that volume and rate of saline infusion are important factors in
      evoking sympathetic activation. We postulate that venous distension contributes
      to cardiovascular autonomic adjustment in humans.

PMID- 21940405
TI  - Effect of macronutrients, age, and obesity on 6- and 24-h postprandial glucose
      metabolism in cats.
AB  - Obesity and age are risk factors for feline diabetes. This study aimed to test
      the hypothesis that age, long-term obesity, and dietary composition would lead to
      peripheral and hepatorenal insulin resistance, indicated by higher endogenous
      glucose production (EGP) in the fasted and postprandial state, higher blood
      glucose and insulin, and higher leptin, free thyroxine, and lower adiponectin
      concentrations. Using triple tracer-(2)H(2)O, [U-(13)C(3)] propionate, and [3,4
      (13)C(2)] glucose infusion, and indirect calorimetry-we investigated carbohydrate
      and fat metabolic pathways in overnight-fasted neutered cats (13 young lean, 12
      old lean, and 12 old obese), each fed three different diets (high protein with
      and without polyunsaturated fatty acids, and high carbohydrate) in a crossover
      design. EGP was lowest in fasted and postprandial obese cats despite peripheral
      insulin resistance, indicated by hyperinsulinemia. Gluconeogenesis was the most
      important pathway for EGP in all groups, but glycogen contributed significantly.
      Insulin and leptin concentrations were higher in old than in young lean cats;
      adiponectin was lowest in obese cats but surprisingly highest in lean old cats.
      Diet had little effect on metabolic parameters. We conclude that hepatorenal
      insulin resistance does not develop in the fasted or postprandial state, even in
      long-term obese cats, allowing the maintenance of euglycemia through lowering
      EGP. Glycogen plays a major role in EGP, especially in lean fasted cats, and in
      the postprandial state. Aging may predispose to insulin resistance, which is a
      risk factor for diabetes in cats. Mechanisms underlying the high adiponectin of
      healthy old lean cats need to be further explored.

PMID- 21940406
TI  - Immunogenicity of recombinant classic swine fever virus CD8(+) T lymphocyte
      epitope and porcine parvovirus VP2 antigen coexpressed by Lactobacillus casei in
      swine via oral vaccination.
AB  - Classical swine fever virus (CSFV) and porcine parvovirus (PPV) are highly
      contagious pathogens, resulting in enormous economic losses in pig industries
      worldwide. Because vaccines play an important role in disease control,
      researchers are seeking improved vaccines that could induce antiviral immune
      responses against CSFV and PPV at the mucosal and systemic levels simultaneously.
      In this study, a genetically engineered Lactobacillus strain coexpressing the
      CSFV-specific cytotoxic T lymphocyte (CTL) epitope 290 and the VP2 antigen of PPV
      was developed, and its immunopotentiating capacity as an oral vaccine in pigs was
      analyzed. The data demonstrated that in the absence of any adjuvant, the
      recombinant Lactobacillus strain can efficiently stimulate mucosal and systemic
      CSFV-specific CD8(+) CTL responses to protect pigs against CSFV challenge.
      Moreover, anti-PPV-VP2 serum IgG and mucosal IgA were induced in pigs immunized
      orally with the recombinant Lactobacillus strain, showing a neutralizing effect
      on PPV infection. The results suggest that the recombinant Lactobacillus
      microecological agent may be a valuable component of a strategy for development
      of a vaccine against CSFV and PPV.

PMID- 21940407
TI  - Studies on porcine circovirus type 2 vaccination of 5-day-old piglets.
AB  - Porcine circovirus type 2 (PCV2) vaccines have become widely used since they
      became available in 2006. It is not uncommon for producers to use PCV2 vaccines
      in pigs younger than what is approved by manufacturers. The objective of this
      study was to determine the efficacy of a chimeric and a subunit PCV2 vaccine
      administered at 5 or 21 days of age. Forty-eight PCV2-naive piglets were randomly
      divided into six groups of eight pigs each. Vaccination was done at day 5 or day
      21, followed by triple challenge with PCV2, porcine parvovirus (PPV), and porcine
      reproductive and respiratory syndrome virus (PRRSV) at day 49. Vaccinated pigs
      seroconverted to PCV2 approximately 14 days postvaccination and had a detectable
      neutralizing antibody response by 21 days postvaccination regardless of age at
      vaccination. At day 49, the pigs vaccinated with the chimeric vaccine had
      significantly higher levels of neutralizing antibodies than the pigs vaccinated
      with the subunit vaccine. After challenge, vaccinated pigs had significantly
      decreased levels of PCV2 viremia and a decreased prevalence and severity of
      microscopic lesions compared to the positive-control group, which had severe
      lymphoid lesions associated with abundant PCV2 antigen, compatible with PCV
      associated disease. The results of this study indicate that, under the conditions
      of this study, vaccination of PCV2-naive pigs at day 5 or day 21 resulted in
      development of a detectable humoral immune response and provided reduction or
      complete protection against PCV2 viremia and PCV2-associated lesions after triple
      challenge with PCV2, PPV, and PRRSV.

PMID- 21940409
TI  - Association of heat-shock protein 70 with lipid rafts is required for Japanese
      encephalitis virus infection in Huh7 cells.
AB  - Japanese encephalitis virus (JEV) is an enveloped flavivirus and the most common
      agent of viral encephalitis. It enters cells through receptor-mediated
      endocytosis and low pH-triggered membrane fusion. Although lipid rafts,
      cholesterol-enriched lipid-ordered membrane domains, have been shown to
      participate in JEV entry, the mechanisms of the early events of JEV infection,
      including the cellular receptors of JEV, remain largely unknown. In the current
      study, it was demonstrated that heat-shock protein 70 (HSP70), rather than other
      members of the HSP70 family, was required for JEV entry into a human cell line.
      Cell-surface expression of HSP70 and a direct interaction between JEV envelope
      (E) protein and HSP70 were observed. Biochemical fractionation showed that HSP70
      clearly migrated into the raft fraction after virus infection and co-fractioned
      with E protein. Depletion of cholesterol shifted the E protein and HSP70 to a non
      raft membrane and decreased JEV entry without affecting virus binding to host
      cells. Notably, recruitment of HSP70 into lipid rafts was required for activation
      of the phosphoinositide 3-kinase/Akt signalling pathway in the early stage of JEV
      infection. These results indicate that lipid rafts facilitate JEV entry, possibly
      by providing a convenient platform to concentrate JEV and its receptors on the
      host-cell membrane.

PMID- 21940408
TI  - Structural gene (prME) chimeras of St Louis encephalitis virus and West Nile
      virus exhibit altered in vitro cytopathic and growth phenotypes.
AB  - Despite utilizing the same avian hosts and mosquito vectors, St Louis
      encephalitis virus (SLEV) and West Nile virus (WNV) display dissimilar vector
      infectivity and vertebrate-pathogenic phenotypes. SLEV exhibits a low oral
      infection threshold for Culex mosquito vectors and is avirulent in avian hosts,
      producing low-magnitude viraemias. In contrast, WNV is less orally infective to
      mosquitoes and elicits high-magnitude viraemias in a wide range of avian species.
      In order to identify the genetic determinants of these different phenotypes and
      to assess the utility of mosquito and vertebrate cell lines for recapitulating in
      vivo differences observed between these viruses, reciprocal WNV and SLEV pre
      membrane and envelope protein (prME) chimeric viruses were generated and growth
      of these mutant viruses was characterized in mammalian (Vero), avian (duck) and
      mosquito [Aedes (C6/36) and Culex (CT)] cells. In both vertebrate lines, WNV grew
      to 100-fold higher titres than SLEV, and growth and cytopathogenicity phenotypes,
      determined by chimeric phenotypes, were modulated by genetic elements outside the
      prME gene region. Both chimeras exhibited distinctive growth patterns from those
      of SLEV in C6/36 cells, indicating the role of both structural and non-structural
      gene regions for growth in this cell line. In contrast, growth of chimeric
      viruses was indistinguishable from that of virus containing homologous prME genes
      in CT cells, indicating that structural genetic elements could specifically
      dictate growth differences of these viruses in relevant vectors. These data
      provide genetic insight into divergent enzootic maintenance strategies that could
      also be useful for the assessment of emergence mechanisms of closely related
      flaviviruses.

PMID- 21940410
TI  - Modulation of lipopolysaccharide receptor expression by lactate dehydrogenase
      elevating virus.
AB  - Lactate dehydrogenase-elevating virus (LDV) exacerbates mouse susceptibility to
      endotoxin shock through enhanced tumour necrosis factor (TNF) production by
      macrophages exposed to lipopolysaccharide (LPS). However, the in vivo enhancement
      of TNF production in response to LPS induced by the virus largely exceeds that
      found in vitro with cells derived from infected animals. Infection was followed
      by a moderate increase of Toll-like receptor (TLR)-4/MD2, but not of membrane
      CD14 expression on peritoneal macrophages. Peritoneal macrophages from LDV
      infected mice unresponsive to type I interferons (IFNs) did not show enhanced
      expression of TLR-4/MD2 nor of CD14, and did not produce more TNF in response to
      LPS than cells from infected normal counterparts, although the in vivo response
      of these animals to LPS was strongly enhanced. In contrast, the virus triggered a
      sharp increase of soluble CD14 and of LPS-binding protein serum levels in normal
      mice. However, production of these LPS soluble receptors was similar in LDV
      infected type I IFN-receptor deficient mice and in their normal counterparts.
      Moreover, serum of LDV-infected mice that contained these soluble receptors had
      little effect if any on cell response to LPS. These results suggest that enhanced
      response of LDV-infected mice to LPS results mostly from mechanisms independent
      of LPS receptor expression.

PMID- 21940411
TI  - Comprehensive mapping of West Nile virus (WNV)- and Japanese encephalitis virus
      serocomplex-specific linear B-cell epitopes from WNV non-structural protein 1.
AB  - West Nile virus (WNV) non-structural protein 1 (NS1) elicits protective immune
      responses during infection of animals. WNV NS1-specific antibody responses can
      provide the basis for serological diagnostic reagents, so the antigenic sites in
      NS1 that are targeted by host immune responses need to be identified and the
      conservation of these sites among the Japanese encephalitis virus (JEV)
      serocomplex members also needs to be defined. The present study describes the
      mapping of linear B-cell epitopes in WNV NS1. We screened eight NS1-specific mAbs
      and antisera (polyclonal antibodies; pAbs) from mice immunized with recombinant
      NS1 for reactivity against 35 partially overlapping peptides covering the entire
      WNV NS1. The screen using mAbs identified four WNV-specific (including Kunjin
      virus) epitopes, located at aa 21-36, 101-116, 191-206 and 261-276 in WNV NS1.
      However, using pAbs, only three WNV-specific epitopes were identified, located at
      positions 101-116, 191-206 and 231-246. Two of these epitopes (aa 21-36 and 261
      276) had different reactivity with mAbs and pAbs. The knowledge and reagents
      generated in this study have potential applications in differential diagnostics
      and epitope-based marker vaccine development for WNV and viruses of the JEV
      serocomplex.

PMID- 21940412
TI  - Seroprevalence of St-Valerien-like caliciviruses in Italian swine.
AB  - St-Valerien-like viruses are newly recognized porcine caliciviruses recently
      detected in North America and Europe. In this study, baculovirus-expressed virus
      like particles of the St-Valerien strain 25A/ITA were generated and used for the
      development of an antibody-detection ELISA kit to assess the seroprevalence of
      these novel caliciviruses in swine. Antibodies specific for St-Valerien-like
      virus were detected in 63 (10.3 %) of 614 serum samples tested with titres
      ranging from 1 : 50 (28.6 %) to 1 : 800 (40.7 %). These results indicate that St
      Valerien-like infections are common among domestic pigs, italy.

PMID- 21940413
TI  - Experimental human rhinovirus and enterovirus interspecies recombination.
AB  - Human rhinoviruses (HRVs) and enteroviruses (HEVs), two important human
      pathogens, are non-enveloped, positive-sense RNA viruses of the genus Enterovirus
      within the family Picornaviridae. Intraspecies recombination is known as a
      driving force for enterovirus and, to a lesser extent, rhinovirus evolution.
      Interspecies recombination is much less frequent among circulating strains, and
      supporting evidence for such recombination is limited to ancestral events, as
      shown by recent phylogenetic analyses reporting ancient HRV-A/HRV-C, HEV-A/HEV-C
      and HEV-A/HEV-D recombination mainly at the 5'-untranslated region (5' UTR)
      polyprotein junction. In this study, chimeric genomes were artificially generated
      using the 5' UTR from two different clinical HRV-C strains (HRV-Ca and HRV-Cc),
      an HRV-B strain (HRV-B37) and an HEV-A strain (HEV-A71), and the remaining part
      of the genome from an HRV-A strain (HRV-A16). Whilst the chimeric viruses were
      easily propagated in cell culture, the wild-type HRV-A16 retained a replication
      advantage, both individually and in competition experiments. Assessment of
      protein synthesis ability did not show a correlation between translation and
      replication efficiencies. These results reflect the interchangeability of the 5'
      UTR, including its functional RNA structural elements implicated in both genome
      translation and replication among different enterovirus species. The 5' UTR
      polyprotein junction therefore represents a theoretic interspecies recombination
      breakpoint. This recombination potential is probably restricted by the need for
      co-infection opportunities and the requirement for the progeny chimera to
      outcompete the parental genomes' fitness, explaining the rare occurrence of such
      events in vivo.

PMID- 21940414
TI  - Intrabronchial inoculation of cynomolgus macaques with cowpox virus.
AB  - The public health threat of orthopoxviruses from bioterrorist attacks has
      prompted researchers to develop suitable animal models for increasing our
      understanding of viral pathogenesis and evaluation of medical countermeasures
      (MCMs) in compliance with the FDA Animal Efficacy Rule. We present an accessible
      intrabronchial cowpox virus (CPXV) model that can be evaluated under biosafety
      level-2 laboratory conditions. In this dose-ranging study, utilizing cynomolgus
      macaques, signs of typical orthopoxvirus disease were observed with the lymphoid
      organs, liver, skin (generally mild) and respiratory tract as target tissues.
      Clinical and histopathological evaluation suggests that intrabronchial CPXV
      recapitulated many of the features of monkeypox and variola virus, the causative
      agent of smallpox, infections in cynomolgus macaque models. These similarities
      suggest that CPXV infection in non-human primates should be pursued further as an
      alternative model of smallpox. Further development of the CPXV primate model,
      unimpeded by select agent and biocontainment restrictions, should facilitate the
      development of MCMs for smallpox.

PMID- 21940415
TI  - JC virus granule cell neuronopathy is associated with VP1 C terminus mutants.
AB  - The polyomavirus JC (JCV) infects glial cells and causes progressive multifocal
      leukoencephalopathy (PML). We described a novel JCV-variant with a 10 bp deletion
      in the C terminus of the VP1 capsid protein, JCV(GCN1). This mutant was
      associated with lytic infection of cerebellar granule cell neurons and cerebellar
      atrophy in an human immunodeficiency virus/PML patient. This condition, also
      observed independently from PML, was named JCV granule cell neuronopathy (JCV
      GCN). We characterized JCV mutations in cerebrospinal fluid (CSF) of four other
      JCV GCN patients, and reviewed the literature on 10 reported cases. The strain
      from one patient harboured the identical GCN1-deletion, while the other patients
      had novel mutations in the same area, named JCV(GCN2-4), causing variable changes
      in VP1 structure. One patient also had wild-type JCV in the CSF. To study the
      mechanisms leading to JCV GCN, we compared viral replication kinetics from
      JCV(GCN1) with the prototype JCV(Mad1), the PML isolate JCV(HWM) and the
      prototype JCV(Mad1D) engineered with the GCN1-deletion. While all strains
      replicated at low levels in the medulloblastoma cell line DAOY from a cerebellar
      neuronal tumour, JCV(Mad1) replicated better in astroglial SVG cells than
      JCV(Mad1D) or JCV(GCN1) and all strains replicated at higher levels in COS-7
      kidney cells, suggesting that the GCN1-deletion confers a disadvantage for viral
      growth in central nervous system white matter. The GCN1-deletion remained stable
      after 100 days in culture and VP1 protein was produced in all cell lines,
      indicating that JCV(GCN1) is replication-competent in vitro. These data highlight
      an important and previously overlooked aspect of JCV-pathogenesis. Detection of
      GCN-type JCV strains in CSF may help clinicians diagnose JCV GCN.

PMID- 21940416
TI  - Managing uncomplicated urinary tract infection--making sense out of resistance
      data.

PMID- 21940417
TI  - Symptom screening among HIV-infected pregnant women is acceptable and has high
      negative predictive value for active tuberculosis.
AB  - We evaluated tuberculosis (TB) screening among 799 human immunodeficiency virus
      (HIV)-infected pregnant women in India. Eleven (1.4%) had active TB. The negative
      predictive value of screening using cough, fever, night sweats, or weight loss
      was 99.3%. Tuberculin skin test and targeted chest radiography provided no
      substantial benefit. TB symptom screening, as recommended by the World Health
      Organization, is effective for ruling out TB in HIV-infected pregnant women.

PMID- 21940418
TI  - Southern Tick-Associated Rash Illness (STARI) in the North: STARI following a
      tick bite in Long Island, New York.
AB  - The most common clinical manifestation of Lyme disease is the characteristic
      rash, erythema migrans (EM). In the 1980s EM-like eruptions were reported in
      Missouri and other southeastern states. The EM-like eruptions, which were of
      unknown etiology, often followed the bite of the Lone Star tick (Amblyomma
      americanum) and the rash is called STARI (southern tick-associated rash illness).
      Although the Lone Star tick is found in the Lyme disease-endemic areas of New
      England and Mid-Atlantic regions of the United States, STARI has been reported
      only once from the Northeast and Mid-Atlantic regions. We report a child from
      Connecticut who visited Long Island, New York, and developed a rash that was
      thought to be EM. Because the patient failed to respond to antibiotics used to
      treat Lyme disease, an investigation ensued, and the diagnosis of STARI was
      established.

PMID- 21940419
TI  - Evaluation of a novel point-of-care cryptococcal antigen test on serum, plasma,
      and urine from patients with HIV-associated cryptococcal meningitis.
AB  - BACKGROUND: Many deaths from cryptococcal meningitis (CM) may be preventable
      through early diagnosis and treatment. An inexpensive point-of-care (POC) assay
      for use with urine or a drop of blood would facilitate early diagnosis of
      cryptococcal infection in resource-limited settings. We compared cryptococcal
      antigen (CRAG) concentrations in plasma, serum, and urine from patients with CM,
      using an antigen-capture assay for glucuronoxylomannan (GXM) and a novel POC
      dipstick test. METHODS: GXM concentrations were determined in paired serum,
      plasma, and urine from 62 patients with active or recent CM, using a quantitative
      sandwich enzyme-linked immunosorbent assay (ELISA). A dipstick lateral-flow assay
      developed using the same monoclonal antibodies for the sandwich ELISA was tested
      in parallel. Correlation coefficients were calculated using Spearman rank test.
      RESULTS: All patients had detectable GXM in serum, plasma, and urine using the
      quantitative ELISA. Comparison of paired serum and plasma showed identical
      results. There were strong correlations between GXM levels in serum/urine (r(s) =
      0.86; P < .001) and plasma/urine (r(s) = 0.85; P < .001). Levels of GXM were 22
      fold lower in urine than in serum/plasma. The dipstick test was positive in
      serum, plasma, and urine in 61 of 62 patients. Dipstick titers correlated
      strongly with ELISA. Correlations between the methods were 0.93 (P < .001) for
      serum, 0.94 (P < .001) for plasma, and 0.94 (P < .001) for urine. CONCLUSIONS:
      This novel dipstick test has the potential to markedly improve early diagnosis of
      CM in many settings, enabling testing of urine in patients presenting to health
      care facilities in which lumbar puncture, or even blood sampling, is not
      feasible.

PMID- 21940420
TI  - Timing of plasmid cytokine (IL-2/Ig) administration affects HIV-1 vaccine
      immunogenicity in HIV-seronegative subjects.
AB  - BACKGROUND: To investigate the potential immunostimulatory effect of interleukin
      (IL) 2 as a human immunodeficiency virus type 1 (HIV-1) vaccine adjuvant, we
      conducted a study of a plasmid coding for a fusion protein of IL-2 and
      immunoglobulin (IL-2/Ig). METHODS: This phase I trial evaluated an HIV-1 DNA
      vaccine with the plasmid cytokine adjuvant (IL-2/Ig) in 70 HIV-negative adults.
      Subjects received placebo (group C), adjuvant alone (group A), vaccine alone
      (group D), increasing doses of adjuvant concurrent with vaccine (groups T1-T4),
      or adjuvant given 2 days after vaccine (group T5). RESULTS: No significant
      differences in adverse events were observed between treatment groups. Cellular
      immune responses to envelope protein EnvA peptides were detected by interferon
      (IFN) gamma and IL-2 enzyme-linked immunospot (ELISPOT) assays in 50% and 40% of
      subjects, respectively, in T4, and in 100% and 80% in T5. The median responses
      for groups T4 and T5, respectively, were 90 and 193 spot-forming cells (SFCs)/106
      peripheral blood mononuclear cells (P = .004; T4 vs T5) for the IL-2 ELISPOT
      assay and 103 and 380 SFCs/106 PBMCs (P = .003; T4 vs T5) for the IFN-gamma
      ELISPOT assay. A trend to more durable cellular immune responses in T5 was
      observed at 1 year (T5 vs T4/D; P = .07). Higher anti-Env antibody responses were
      detected with T5 than with T4. CONCLUSIONS: Plasmid IL-2/Ig significantly
      increased immune responses when administered 2 days after the DNA vaccine,
      compared with simultaneous administration. These observations have important
      implications for the development of cytokine augmentation strategies. CLINICAL
      TRIALS REGISTRATION: NCT00069030.

PMID- 21940421
TI  - Cortistatin is induced in brain tissue and exerts neuroprotection in a rat model
      of bacterial meningoencephalitis.
AB  - There are fewer reports of brain infection by Klebsiella pneumoniae than there
      are in other organs, but an increase incidence and morbidity has been noted. We
      have previously developed a rat model of K. pneumoniae meningoencephalitis.
      Cortistatin (CST) is a recently discovered neuropeptide with endocrine activities
      in humans. In this study, we found that brain infection by K. pneumoniae
      increased endogenous prepro-CST messenger RNA expression, which occurred earlier
      than did leukocyte infiltration in vivo and also occurred in cultured neuron
      glia. Postinfection treatment with CST (either intracerebroventricularly or
      intraperitoneally), but not somatostatin, reduced leukocyte recruitment and
      clinical illness as revealed by fever and clinical score in vivo. Postinfection
      increases of proinflammatory cytokine messenger RNA levels were attenuated by CST
      in neuron-glia cultures, further confirming a direct effect on neuroinflammation.
      Administration of CST resulted in less postinfection neuronal loss in vitro,
      suggesting a direct neuroprotective effect and potential as an adjuvant for
      treating bacterial meningoencephalitis.

PMID- 21940422
TI  - Immune activation in the female genital tract during HIV infection predicts
      mucosal CD4 depletion and HIV shedding.
AB  - Plasma viral load predicts genital tract human immunodeficiency virus (HIV)
      shedding in HIV-infected women. We investigated whether local mucosal T-cell
      activation (HLA-DR, CD38, CCR5, and Ki67) contributed to HIV shedding in the
      genital tracts of HIV-infected women. We showed that cervical cytobrush-derived T
      cells expressed higher frequencies of T-cell activation markers (CD38+ and HLA
      DR+) than blood-derived T cells. Expression was significantly higher in HIV
      infected women than in uninfected women. We found that the frequency of activated
      proliferating cervical T cells (Ki67+; Ki67+CCR5+) broadly predicted HIV shedding
      in the genital tract in HIV-infected women, independently of plasma viral loads.
      Furthermore, activated cervical T cells (HLA-DR+CD38+ and HLA-DR+CCR5+) and local
      HIV shedding were independently associated with CD4 depletion in the genital
      tract. These data suggest that the presence of high frequencies of activated T
      cells in the female genital mucosa during HIV infection facilitates both local
      HIV shedding and CD4 T-cell depletion.

PMID- 21940423
TI  - Laypeople's ethical concerns about a New Israeli organ transplantation
      prioritization policy aimed to encourage organ donor registration among the
      public.
AB  - A new policy recently enacted in Israel promises preferred status in receiving
      organs for transplantation to individuals who register to be organ donors and to
      their close family members. Proponents believe it will increase the supply of
      organs for transplantation from the deceased. Ethical issues were raised in
      government committees appointed to discuss the policy before its approval, but
      discussions among laypeople were not solicited. This study aimed to elicit
      laypeople's views about the policy by conducting thirteen group interviews and
      thirty-six individual interviews. Participants included religious and
      nonreligious people, immigrants, and Arabs. Some participants thought the law
      would contribute to fairness by prioritizing those willing to give, but others
      articulated ethical concerns that were not emphasized by scholars, in particular
      that the policy would add to the erosion of social solidarity, increase
      divisiveness, and enable people to abuse the system. Mistrust in the health care
      system emerged as a prominent reason for not registering as an organ donor.
      Implications about the importance of transparency in the organ transplantation
      system as a basis for an information campaign, social norms regarding organ
      donation, and the public's involvement in policy issues on organ donation are
      discussed.

PMID- 21940424
TI  - Addressing the shortage of kidneys for transplantation: purchase and allocation
      through chain auctions.
AB  - Transplantation is generally the treatment of choice for those suffering from
      kidney failure. Not only does transplantation offer improved quality of life and
      increased longevity relative to dialysis, it also reduces end-stage renal disease
      program expenditures, providing savings to Medicare. Unfortunately, the waiting
      list for kidney transplants is long, growing, and unlikely to be substantially
      reduced by increases in the recovery of cadaveric kidneys. Another approach is to
      obtain more kidneys through payment to living "donors," or vendors. Such direct
      commodification, in which a price is placed on kidneys, has generally been
      opposed by medical ethicists. Much of the ethical debate, however, has been in
      terms of commodification through market exchange. Recognizing that there are
      different ethical concerns associated with the purchase of kidneys and their
      allocation, it is possible to design a variety of institutional arrangements for
      the commodification of kidneys that pose different sets of ethical concerns. We
      specify three such alternatives in detail sufficient to allow an assessment of
      their likely consequences and we compare these alternatives to current policy in
      terms of the desirable goals of promoting human dignity, equity, efficiency, and
      fiscal advantage. This policy analysis leads us to recommend that kidneys be
      purchased at administered prices by a nonprofit organization and allocated to the
      transplant centers that can organize the longest chains of transplants involving
      willing-but-incompatible donor-patient dyads.

PMID- 21940425
TI  - The angel is in the details.

PMID- 21940426
TI  - Dehumanizing a most human practice.

PMID- 21940427
TI  - The Turkish version of the breastfeeding attrition prediction tool.
AB  - This study demonstrates that the original English version of the Breastfeeding
      Attrition Prediction Tool (BAPT) was successfully adapted to Turkey, as
      methodologically demonstrated here. The results of this study show that the
      Turkish version of the BAPT is similar to the original version and that it can be
      used with Turkish women to identify mothers who may be at high risk of weaning
      prematurely.

PMID- 21940428
TI  - Nociceptive memory in the brain: cortical mechanisms of chronic pain.

PMID- 21940429
TI  - Opioidergic interactions between striatal projection neurons.
AB  - Medium spiny striatal projection neurons (MSNs) release opioid neuropeptides, but
      the role of these neurotransmitters is still poorly understood. While presynaptic
      inhibition of corticostriatal axons by opioid receptors has been demonstrated
      using exogenous ligands, the action of synaptically released opioids in the
      striatum has not been investigated. We performed single and paired whole-cell
      recordings from rat MSNs while corticostriatal fibers were electrically
      activated. In single recording experiments, we also activated antidromically the
      axons of a population of MSNs. Corticostriatal fibers were stimulated once every
      10 s and every other stimulation was preceded by 5 antidromic spikes (at 100 Hz).
      This burst of antidromic spikes produced robust inhibition of evoked
      corticostriatal responses. This inhibition was not affected by the delta-opioid
      receptor antagonist SDM25N, but was completely abolished by the MU-opioid
      receptor antagonist CTOP. Inhibitory effects were maximal (on average 29.6 +/-
      11.4%) when the burst preceded the corticostriatal stimulation by 500 ms and
      became undetectable for intervals >2 s. Paired recordings from MSNs located <100
      MUm apart revealed that, in 30 of 56 (54%) pairs, a burst of five action
      potentials in one of the MSNs caused significant inhibition (17.1 +/- 5.7%) of
      evoked glutamatergic responses in the other MSN. In 5 of these pairs, reciprocal
      inhibition of corticostriatal inputs was present. These effects were maximal 500
      ms after the burst and were completely blocked by CTOP. Thus, these results
      reveal a novel, strong opioid-mediated communication between MSNs and provide a
      new cellular substrate for competitive dynamics in the striatum.

PMID- 21940430
TI  - Complementary function and integrated wiring of the evolutionarily distinct
      Drosophila olfactory subsystems.
AB  - To sense myriad environmental odors, animals have evolved multiple, large
      families of divergent olfactory receptors. How and why distinct receptor
      repertoires and their associated circuits are functionally and anatomically
      integrated is essentially unknown. We have addressed these questions through
      comprehensive comparative analysis of the Drosophila olfactory subsystems that
      express the ionotropic receptors (IRs) and odorant receptors (ORs). We identify
      ligands for most IR neuron classes, revealing their specificity for select amines
      and acids, which complements the broader tuning of ORs for esters and alcohols.
      IR and OR sensory neurons exhibit glomerular convergence in segregated, although
      interconnected, zones of the primary olfactory center, but these circuits are
      extensively interdigitated in higher brain regions. Consistently, behavioral
      responses to odors arise from an interplay between IR- and OR-dependent pathways.
      We integrate knowledge on the different phylogenetic and developmental properties
      of these receptors and circuits to propose models for the functional
      contributions and evolution of these distinct olfactory subsystems.

PMID- 21940432
TI  - Morphological and functional continuum underlying heterogeneity in the spiking
      fidelity at the calyx of Held synapse in vitro.
AB  - Reliable neuronal spiking is critical for a myriad of computations performed by
      neural circuits. This is particularly evident for sound localization cues in the
      auditory brainstem circuits that detect timing and intensity differences of
      sounds arriving at two ears. The calyx of Held-principal neuron synapse in the
      medial nucleus of the trapezoid body (MNTB) in this circuit is traditionally
      viewed as a reliable relay, which converts contralateral excitatory inputs to
      inhibitory outputs to ipsilateral superior olive neurons that code interaural
      timing and intensity differences. However, recent studies demonstrated large
      variability in the incidence of postsynaptic spike failures at this synapse,
      challenging the view that this synapse is a fail-safe relay. Using combined
      imaging and paired recordings in mature (P16-P19) mouse brainstem slices, we show
      that spike failure rates of MNTB neurons are strongly correlated with differences
      in gross morphology of the calyx terminal and quantal properties under standard
      in vitro- and in vivo-like conditions. MNTB neurons innervated by calyces with
      simple morphologies (mainly digits) express strong short-term synaptic depression
      and a high incidence of spike failures after high-frequency stimulation.
      Conversely, MNTB neurons innervated by structurally complex calyces (digits and
      numerous bouton-like swellings) exhibit initial facilitation followed by slow
      depression and very few spike failures. Our results indicate that the calyx of
      Held-MNTB synapse is likely organized as a structural and functional continuum,
      in that correlated heterogeneities in calyx morphology and short-term plasticity
      serve as a filter for regulating the inhibition delivered to superior olive
      neurons during sound localization.

PMID- 21940431
TI  - The unfolded protein response is a major mechanism by which LRP1 regulates
      Schwann cell survival after injury.
AB  - In peripheral nerve injury, Schwann cells (SCs) must survive to exert a
      continuing and essential role in successful nerve regeneration. Herein, we show
      that peripheral nerve injury is associated with activation of endoplasmic
      reticulum (ER) stress and the adaptive unfolded protein response (UPR). The UPR
      culminates in expression of C/EBP homology protein (CHOP), a proapoptotic
      transcription factor in SCs, unless counteracted by LDL receptor-related protein
      1 (LRP1), which serves as a major activator of phosphatidylinositol 3-kinase
      (PI3K). Sciatic nerve crush injury in rats induced expression of the ER chaperone
      GRP78/BIP, reflecting an early, corrective phase of the UPR. However, when LRP1
      signaling was inhibited with receptor-associated protein, PI3K activity was
      decreased and CHOP protein expression increased, particularly in myelinating SCs.
      In cultured SCs, the PKR-like ER kinase target eIF2alpha was phosphorylated and
      CHOP was induced by (1) inhibiting PI3K, (2) treating the cells with tumor
      necrosis factor-alpha (TNF-alpha), or (3) genetic silencing of LRP1. CHOP gene
      deletion in SCs decreased cell death in response to TNF-alpha. Furthermore, the
      effects of TNF-alpha on phosphorylated eIF2alpha, CHOP, and SC death were blocked
      by adding LRP1 ligands that augment LRP1-dependent cell signaling to PI3K.
      Collectively, our results support a model in which UPR-activated signaling
      pathways represent a major challenge to SC survival in nerve injury. LRP1
      functions as a potent activator of PI3K in SCs and, by this mechanism, limits SC
      apoptosis resulting from increased CHOP expression in nerve injury.

PMID- 21940433
TI  - Cocaine alters BDNF expression and neuronal migration in the embryonic mouse
      forebrain.
AB  - Prenatal cocaine exposure impairs brain development and produces lasting
      alterations in cognitive function. In a prenatal cocaine exposure mouse model, we
      found that tangential migration of GABA neurons from the basal to the dorsal
      forebrain and radial neuron migration within the dorsal forebrain were
      significantly decreased during the embryonic period. The decrease in the
      tangential migration occurred early in gestation and normalized by late
      gestation, despite ongoing cocaine exposure. The decrease in radial migration was
      associated with altered laminar positioning of neurons in the medial prefrontal
      cortex. The cocaine exposure led to transient decreases in the expression of Tbr2
      and Tbr1, transcription factors associated with intermediate progenitor cells and
      newborn neurons of the dorsal forebrain, respectively, although neurogenesis was
      not significantly altered. Since cocaine can modulate brain derived neurotrophic
      factor (BDNF) expression in the mature brain, we examined whether cocaine can
      alter BDNF expression in the embryonic brain. We found a transient decrease in
      BDNF protein expression in the cocaine-exposed embryonic forebrain early in
      gestation. By late gestation, the BDNF expression recovered to control levels,
      despite ongoing cocaine exposure. In basal forebrain explants from cocaine
      exposed embryos, cell migration was significantly decreased, corroborating the in
      vivo data on tangential GABA neuron migration. Since BDNF can influence
      tangential neuronal migration, we added BDNF to the culture medium and observed
      increased cell migration. Our data suggest that cocaine can alter tangential and
      radial neuronal migration as well as BDNF expression in the embryonic brain and
      that decreased BDNF may mediate cocaine's effects on neuronal migration.

PMID- 21940434
TI  - Lipocalin 2 plays an immunomodulatory role and has detrimental effects after
      spinal cord injury.
AB  - Lipocalin 2 (Lcn2) plays an important role in defense against bacterial infection
      by interfering with bacterial iron acquisition. Although Lcn2 is expressed in a
      number of aseptic inflammatory conditions, its role in these conditions remains
      unclear. We examined the expression and role of Lcn2 after spinal cord injury
      (SCI) in adult mice by using a contusion injury model. Lcn2 expression at the
      protein level is rapidly increased 12-fold at 1 d after SCI and decreases
      gradually thereafter, being three times as high as control levels at 21 d after
      injury. Lcn2 expression is strongly induced after contusion injury in astrocytes,
      neurons, and neutrophils. The Lcn2 receptor (Lcn2R), which has been shown to
      influence cell survival, is also expressed after SCI in the same cell types. Lcn2
      deficient (Lcn2-/-) mice showed significantly better locomotor recovery after
      spinal cord contusion injury than wild-type (Lcn2+/+) mice. Histological
      assessments indicate improved neuronal and tissue survival and greater sparing of
      myelin in Lcn2-/- mice after contusion injury. Flow cytometry showed a decrease
      in neutrophil influx and a small increase in the monocyte population in Lcn2-/-
      injured spinal cords. This change was accompanied by a reduction in the
      expression of several pro-inflammatory chemokines and cytokines as well as
      inducible nitric oxide synthase early after SCI in Lcn2-/- mice compared with
      wild-type animals. Our results, therefore, suggest a role for Lcn2 in regulating
      inflammation in the injured spinal cord and that lack of Lcn2 reduces secondary
      damage and improves locomotor recovery after spinal cord contusion injury.

PMID- 21940435
TI  - Alterations of endocannabinoid signaling, synaptic plasticity, learning, and
      memory in monoacylglycerol lipase knock-out mice.
AB  - Endocannabinoid (eCB) signaling is tightly regulated by eCB biosynthetic and
      degradative enzymes. The eCB 2-arachidonoylglycerol (2-AG) is hydrolyzed
      primarily by monoacylglycerol lipase (MAGL). Here, we investigated whether eCB
      signaling, synaptic function, and learning behavior were altered in MAGL knock
      out mice. We report that MAGL-/- mice exhibited prolonged depolarization-induced
      suppression of inhibition (DSI) in hippocampal CA1 pyramidal neurons, providing
      genetic evidence that the inactivation of 2-AG by MAGL determines the time course
      of the eCB-mediated retrograde synaptic depression. CB1 receptor antagonists
      enhanced basal IPSCs in CA1 pyramidal neurons in MAGL-/- mice, while the
      magnitude of DSI or CB1 receptor agonist-induced depression of IPSCs was
      decreased in MAGL-/- mice. These results suggest that 2-AG elevations in MAGL-/-
      mice cause tonic activation and partial desensitization of CB1 receptors. Genetic
      deletion of MAGL selectively enhanced theta burst stimulation (TBS)-induced long
      term potentiation (LTP) in the CA1 region of hippocampal slices but had no
      significant effect on LTP induced by high-frequency stimulation or long-term
      depression induced by low-frequency stimulation. The enhancement of TBS-LTP in
      MAGL-/- mice appears to be mediated by 2-AG-induced suppression of GABA(A)
      receptor-mediated inhibition. MAGL-/- mice exhibited enhanced learning as shown
      by improved performance in novel object recognition and Morris water maze. These
      results indicate that genetic deletion of MAGL causes profound changes in eCB
      signaling, long-term synaptic plasticity, and learning behavior.

PMID- 21940436
TI  - Glutamate spillover between mammalian cone photoreceptors.
AB  - Cone photoreceptors transmit signals at high temporal frequencies and mediate
      fine spatial vision. High-frequency transmission requires a high rate of
      glutamate release, which could promote spillover to neighboring cells, whereas
      spatial vision requires that cones within a tightly packed array signal light to
      postsynaptic bipolar cells with minimal crosstalk. Glutamate spread from the cone
      terminal is thought to be limited by presynaptic transporters and nearby glial
      processes. In addition, there is no ultrastructural evidence for chemical
      synapses between mammalian cones, although such synapses have been described in
      lower vertebrate retinas. We tested for cone-cone glutamate diffusion by
      recording from adjacent cone pairs in the ground squirrel retina, and instead
      found that the glutamate released by one cone during electrical stimulation
      activates glutamate transporter Cl(-) conductances on neighboring cones. Unlike
      in other systems, where crosstalk is diminished by increasing the temperature and
      by moving to a more intact preparation, glutamate spread persisted at
      physiological temperatures (37 degrees C) and in retinal flat mounts. The
      glutamate-gated anion conductance in cones has a reversal potential of ~-30 mV
      compared with a cone resting potential of ~-50 mV; thus, crosstalk should have a
      depolarizing effect on the cone network. Cone-cone glutamate spread is regulated
      by the physiological stimulus, light, and under physiological conditions can
      produce a response of ~2 mV, equivalent to 13-20% of a cone's light response. We
      conclude that in the absence of discrete chemical synapses, glutamate flows
      between cones during a light response and may mediate a spatially distributed
      positive feedback.

PMID- 21940437
TI  - Default mode network connectivity predicts sustained attention deficits after
      traumatic brain injury.
AB  - Traumatic brain injury (TBI) frequently produces impairments of attention in
      humans. These can result in a failure to maintain consistent goal-directed
      behavior. A predominantly right-lateralized frontoparietal network is often
      engaged during attentionally demanding tasks. However, lapses of attention have
      also been associated with increases in activation within the default mode network
      (DMN). Here, we study TBI patients with sustained attention impairment, defined
      on the basis of the consistency of their behavioral performance over time. We
      show that sustained attention impairments in patients are associated with an
      increase in DMN activation, particularly within the precuneus and posterior
      cingulate cortex. Furthermore, the interaction of the precuneus with the rest of
      the DMN at the start of the task, i.e., its functional connectivity, predicts
      which patients go on to show impairments of attention. Importantly, this
      predictive information is present before any behavioral evidence of sustained
      attention impairment, and the relationship is also found in a subgroup of
      patients without focal brain damage. TBI often results in diffuse axonal injury,
      which produces cognitive impairment by disconnecting nodes in distributed brain
      networks. Using diffusion tensor imaging, we demonstrate that structural
      disconnection within the DMN also correlates with the level of sustained
      attention. These results show that abnormalities in DMN function are a sensitive
      marker of impairments of attention and suggest that changes in connectivity
      within the DMN are central to the development of attentional impairment after
      TBI.

PMID- 21940438
TI  - Tinnitus with a normal audiogram: physiological evidence for hidden hearing loss
      and computational model.
AB  - Ever since Pliny the Elder coined the term tinnitus, the perception of sound in
      the absence of an external sound source has remained enigmatic. Traditional
      theories assume that tinnitus is triggered by cochlear damage, but many tinnitus
      patients present with a normal audiogram, i.e., with no direct signs of cochlear
      damage. Here, we report that in human subjects with tinnitus and a normal
      audiogram, auditory brainstem responses show a significantly reduced amplitude of
      the wave I potential (generated by primary auditory nerve fibers) but normal
      amplitudes of the more centrally generated wave V. This provides direct
      physiological evidence of "hidden hearing loss" that manifests as reduced neural
      output from the cochlea, and consequent renormalization of neuronal response
      magnitude within the brainstem. Employing an established computational model, we
      demonstrate how tinnitus could arise from a homeostatic response of neurons in
      the central auditory system to reduced auditory nerve input in the absence of
      elevated hearing thresholds.

PMID- 21940439
TI  - The functional link between area MT neural fluctuations and detection of a brief
      motion stimulus.
AB  - Fluctuations of neural firing rates in visual cortex are known to be correlated
      with variations in perceptual performance. It is important to know whether these
      fluctuations are functionally linked to perception in a causal manner or instead
      reflect non-causal processes that arise after the perceptual decision is made. We
      recorded from middle temporal (MT) neurons from monkey subjects while they
      detected the random occurrence of a brief 50 ms motion pulse that occurred in
      either of two (or simultaneously in both) random dot patches located in the same
      hemisphere. The receptive field parameters of the motion pulse were matched to
      that preferred by each MT neuron under study. This task contained uncertainty in
      both space and time because, on any given trial, the subjects did not know which
      patch would contain the motion pulse or when the motion pulse would occur.
      Covariations between MT activity and behavior began just before the motion pulse
      onset and peaked at the maximum neural response. These neural-behavioral
      covariations were strongest when only one patch contained the motion pulse and
      were still weakly present when a patch did not contain a motion pulse. A
      feedforward temporal integration model with two independent detector channels
      captured both the detection performance and evolution of the neural-behavior
      covariations over time and stimulus condition. The results suggest that, when
      detecting a brief visual stimulus, there is a causal relationship between
      fluctuations in neural activity and variations in behavior across trials.

PMID- 21940440
TI  - Stimulation of entorhinal cortex promotes adult neurogenesis and facilitates
      spatial memory.
AB  - Deep brain stimulation (DBS) is an established therapeutic modality for the
      treatment of movement disorders and an emerging therapeutic approach for the
      treatment of disorders of mood and thought. For example, recently we have shown
      that DBS of the fornix may ameliorate cognitive decline associated with dementia.
      However, like other applications of DBS, the mechanisms mediating these clinical
      effects are unknown. As DBS modulates neurophysiological activity in targeted
      brain regions, DBS might influence cognitive function via activity-dependent
      regulation of hippocampal neurogenesis. Using stimulation parameters analogous to
      clinical high-frequency DBS, here we addressed this question in mice. We found
      that acute stimulation of the entorhinal cortex (EC) transiently promoted
      proliferation in the dentate gyrus (DG). Cells generated as a consequence of
      stimulation differentiated into neurons, survived for at least several weeks, and
      acquired normal dentate granule cell (DGC) morphology. Importantly, stimulation
      induced promotion of neurogenesis was limited to the DG and not associated with
      changes in apoptotic cell death. Using immunohistochemical approaches, we found
      that, once sufficiently mature, these stimulation-induced neurons integrated into
      hippocampal circuits supporting water-maze memory. Finally, formation of water
      maze memory was facilitated 6 weeks (but not 1 week) after bilateral stimulation
      of the EC. The delay-dependent nature of these effects matches the maturation
      dependent integration of adult-generated DGCs into dentate circuits supporting
      water-maze memory. Furthermore, because the beneficial effects of EC stimulation
      were prevented by blocking neurogenesis, this suggests a causal relationship
      between stimulation-induced promotion of adult neurogenesis and enhanced spatial
      memory.

PMID- 21940441
TI  - IL-1 receptor accessory protein-like 1 associated with mental retardation and
      autism mediates synapse formation by trans-synaptic interaction with protein
      tyrosine phosphatase delta.
AB  - Mental retardation (MR) and autism are highly heterogeneous neurodevelopmental
      disorders. IL-1-receptor accessory protein-like 1 (IL1RAPL1) is responsible for
      nonsyndromic MR and is associated with autism. Thus, the elucidation of the
      functional role of IL1RAPL1 will contribute to our understanding of the
      pathogenesis of these mental disorders. Here, we showed that knockdown of
      endogenous IL1RAPL1 in cultured cortical neurons suppressed the accumulation of
      punctate staining signals for active zone protein Bassoon and decreased the
      number of dendritic protrusions. Consistently, the expression of IL1RAPL1 in
      cultured neurons stimulated the accumulation of Bassoon and spinogenesis. The
      extracellular domain (ECD) of IL1RAPL1 was required and sufficient for the
      presynaptic differentiation-inducing activity, while both the ECD and cytoplasmic
      domain were essential for the spinogenic activity. Notably, the synaptogenic
      activity of IL1RAPL1 was specific for excitatory synapses. Furthermore, we
      identified presynaptic protein tyrosine phosphatase (PTP) delta as a major
      IL1RAPL1-ECD interacting protein by affinity chromatography. IL1RAPL1 interacted
      selectively with certain forms of PTPdelta splice variants carrying mini-exon
      peptides in Ig-like domains. The synaptogenic activity of IL1RAPL1 was abolished
      in primary neurons from PTPdelta knock-out mice. IL1RAPL1 showed robust
      synaptogenic activity in vivo when transfected into the cortical neurons of wild
      type mice but not in PTPdelta knock-out mice. These results suggest that IL1RAPL1
      mediates synapse formation through trans-synaptic interaction with PTPdelta. Our
      findings raise an intriguing possibility that the impairment of synapse formation
      may underlie certain forms of MR and autism as a common pathogenic pathway shared
      by these mental disorders.

PMID- 21940442
TI  - Neurexin-neuroligin adhesions capture surface-diffusing AMPA receptors through
      PSD-95 scaffolds.
AB  - The mechanisms governing the recruitment of functional glutamate receptors at
      nascent excitatory postsynapses following initial axon-dendrite contact remain
      unclear. We examined here the ability of neurexin/neuroligin adhesions to
      mobilize AMPA-type glutamate receptors (AMPARs) at postsynapses through a
      diffusion/trap process involving the scaffold molecule PSD-95. Using single
      nanoparticle tracking in primary rat and mouse hippocampal neurons overexpressing
      or lacking neuroligin-1 (Nlg1), a striking inverse correlation was found between
      AMPAR diffusion and Nlg1 expression level. The use of Nlg1 mutants and inhibitory
      RNAs against PSD-95 demonstrated that this effect depended on intact Nlg1/PSD-95
      interactions. Furthermore, functional AMPARs were recruited within 1 h at nascent
      Nlg1/PSD-95 clusters assembled by neurexin-1beta multimers, a process requiring
      AMPAR membrane diffusion. Triggering novel neurexin/neuroligin adhesions also
      caused a depletion of PSD-95 from native synapses and a drop in AMPAR miniature
      EPSCs, indicating a competitive mechanism. Finally, both AMPAR level at synapses
      and AMPAR-dependent synaptic transmission were diminished in hippocampal slices
      from newborn Nlg1 knock-out mice, confirming an important role of Nlg1 in driving
      AMPARs to nascent synapses. Together, these data reveal a mechanism by which
      membrane-diffusing AMPARs can be rapidly trapped at PSD-95 scaffolds assembled at
      nascent neurexin/neuroligin adhesions, in competition with existing synapses.

PMID- 21940443
TI  - An autocrine neuronal interleukin-6 loop mediates chloride accumulation and NKCC1
      phosphorylation in axotomized sensory neurons.
AB  - The cation-chloride cotransporter NKCC1 plays a fundamental role in the central
      and peripheral nervous systems by setting the value of intracellular chloride
      concentration. Following peripheral nerve injury, NKCC1 phosphorylation-induced
      chloride accumulation contributes to neurite regrowth of sensory neurons.
      However, the molecules and signaling pathways that regulate NKCC1 activity remain
      to be identified. Functional analysis of cotransporter activity revealed that
      inhibition of endogenously produced cytokine interleukin-6 (IL-6), with anti
      mouse IL-6 antibody or in IL-6-/- mice, prevented chloride accumulation in a
      subset of axotomized neurons. Nerve injury upregulated the transcript and protein
      levels of IL-6 receptor in myelinated, TrkB-positive sensory neurons of murine
      lumbar dorsal root ganglia. Expression of phospho-NKCC1 was observed mainly in
      sensory neurons expressing IL-6 receptor and was absent from IL-6-/- dorsal root
      ganglia. The use of IL-6 receptor blocking-function antibody or soluble IL-6
      receptor, together with pharmacological inhibition of Janus kinase, confirmed the
      role of neuronal IL-6 signaling in chloride accumulation and neurite growth of a
      subset of axotomized sensory neurons. Cell-specific expression of interleukin-6
      receptor under pathophysiological conditions is therefore a cellular response by
      which IL-6 contributes to nerve regeneration through neuronal NKCC1
      phosphorylation and chloride accumulation.

PMID- 21940444
TI  - Behavioral evidence for a glucose polymer taste receptor that is independent of
      the T1R2+3 heterodimer in a mouse model.
AB  - Although it is clear that the heterodimer formed by the T1R2 and T1R3 proteins
      serves as the primary taste receptor for sweeteners, there is growing evidence
      that responses to glucose polymers may be mediated by a different taste receptor.
      Here we report that although T1R2 knock-out (KO) and T1R3 KO mice displayed
      severely impaired responding to glucose, maltose, and maltotriose in an initial
      session of a brief-access taste test (5 s trials, 25 min sessions) relative to
      wild-type (WT) mice, they subsequently increased their licking as a function of
      concentration for maltose and maltotriose with continued testing, presumably due
      to associating weak oral cues with positive post-ingestive consequences.
      Interestingly, these KO mice displayed relatively normal concentration-dependent
      licking to Polycose, a mixture of glucose polymers, even in the first session.
      Importantly, the experience-dependent increase in responsiveness to the sugars
      observed with the T1R2 and T1R3 single KO mice was not statistically significant
      in the T1R2/3 double KO mice. The double KO mice, however, still displayed
      significant concentration-dependent responding to Polycose in the first test
      session, albeit lick rates were slightly lower than those seen for WT mice,
      perhaps because small amounts of glucose, maltose, and maltotriose found in
      Polycose were enhancing the signal in WT mice or because T1R2 or T1R3 can
      possibly heteromerize with another protein to form a fully functional glucose
      polymer receptor. These findings provide behavioral evidence that glucose
      polymers, with an optimal chain length greater than three glucose moieties,
      stimulate a taste receptor independent of the T1R2+3 heterodimer.

PMID- 21940445
TI  - Semantic analysis does not occur in the absence of awareness induced by
      interocular suppression.
AB  - It has been intensely debated whether visual stimuli are processed to the point
      of semantic analysis in the absence of awareness. In the present study, we
      measured the extent to which the meaning of a stimulus was registered using the
      N400 component of human event-related potentials (ERPs), a highly sensitive index
      of the semantic mismatch between a stimulus and the context in which it is
      presented. Observers judged the semantic relatedness of a context and target word
      while ERPs were recorded under continuous flash suppression (Experiments 1 and 2)
      and binocular rivalry (Experiment 3). Finally, we parametrically manipulated the
      visibility of the target word by increasing the contrast between the target word
      and the suppressive stimulus presented to the other eye (Experiment 4). We found
      that the amplitude of the N400 was attenuated with increasing suppression depth
      and was absent whenever the observers could not discriminate the meaning of
      suppressed words. We discuss these findings in the context of single-process
      models of consciousness, which can account for a large body of empirical evidence
      obtained from visual masking, attentional manipulations, and, now, interocular
      suppression paradigms.

PMID- 21940446
TI  - Nerve terminal nicotinic acetylcholine receptors initiate quantal GABA release
      from perisomatic interneurons by activating axonal T-type (Cav3) Ca2+ channels
      and Ca2+ release from stores.
AB  - Release of conventional neurotransmitters is mainly controlled by calcium (Ca2+)
      influx via high-voltage-activated (HVA), Ca(v)2, channels ("N-, P/Q-, or R
      types") that are opened by action potentials. Regulation of transmission by
      subthreshold depolarizations does occur, but there is little evidence that low
      voltage-activated, Ca(v)3 ("T-type"), channels take part. GABA release from
      cortical perisomatic-targeting interneurons affects numerous physiological
      processes, and yet its underlying control mechanisms are not fully understood. We
      investigated whether T-type Ca2+ channels are involved in regulating GABA
      transmission from these cells in rat hippocampal CA1 using a combination of whole
      cell voltage-clamp, multiple-fluorescence confocal microscopy, dual
      immunolabeling electron-microscopy, and optogenetic methods. We show that
      Ca(v)3.1, T-type Ca2+ channels can be activated by alpha3beta4 nicotinic
      acetylcholine receptors (nAChRs) that are located on the synaptic regions of the
      GABAergic perisomatic-targeting interneuronal axons, including the parvalbumin
      expressing cells. Asynchronous, quantal GABA release can be triggered by Ca2+
      influx through presynaptic T-type Ca2+ channels, augmented by Ca2+ from internal
      stores, following focal microiontophoretic activation of the alpha3beta4 nAChRs.
      The resulting GABA release can inhibit pyramidal cells. The T-type Ca2+ channel
      dependent mechanism is not dependent on, or accompanied by, HVA channel Ca2+
      influx, and is insensitive to agonists of cannabinoid, MU-opioid, or GABA(B)
      receptors. It may therefore operate in parallel with the normal HVA-dependent
      processes. The results reveal new aspects of the regulation of GABA transmission
      and contribute to a deeper understanding of ACh and nicotine actions in CNS.

PMID- 21940448
TI  - Transfer of learned manipulation following changes in degrees of freedom.
AB  - The present study was designed to determine whether manipulation learned with a
      set of digits can be transferred to grips involving a different number of digits,
      and possible mechanisms underlying such transfer. The goal of the task was to
      exert a torque and vertical forces on a visually symmetrical object at object
      lift onset to balance the external torque caused by asymmetrical mass
      distribution. Subjects learned this manipulation through consecutive practice
      using one grip type (two or three digits), after which they performed the same
      task but with another grip type (e.g., after adding or removing one digit,
      respectively). Subjects were able to switch grip type without compromising the
      behavioral outcome (i.e., the direction, timing, and magnitude of the torque
      exerted on the object was unchanged), despite the use of significantly different
      digit force-position coordination patterns in the two grip types. Our results
      support the transfer of learning for anticipatory control of manipulation and
      indicate that the CNS forms an internal model of the manipulation task
      independent of the effectors that are used to learn it. We propose that sensory
      information about the new digit placement--resulting from adding or removing a
      digit immediately after the switch in grip type--plays an important role in the
      accurate modulation of new digit force distributions. We discuss our results in
      relation to studies of manipulation reporting lack of learning transfer and
      propose a theoretical framework that accounts for failure or success of motor
      learning generalization.

PMID- 21940447
TI  - Cav1.2 L-type Ca2+ channels mediate cocaine-induced GluA1 trafficking in the
      nucleus accumbens, a long-term adaptation dependent on ventral tegmental area
      Ca(v)1.3 channels.
AB  - AMPA receptor (AMPAR) plasticity at glutamatergic synapses in the mesoaccumbal
      dopaminergic pathway has been implicated in persistent cocaine-induced behavioral
      responses; however, the precise mechanism underlying these changes remains
      unknown. Utilizing cocaine psychomotor sensitization, we have examined
      phosphorylation of GluA1 at key residues serine 845 (S845) and S831, as well as
      GluA1 cell surface levels in the nucleus accumbens (NAc) of cocaine-preexposed
      mice and the role of brain-specific Ca(v)1.2 and Ca(v)1.3 L-type Ca2+ channels
      (LTCCs), therein. We found higher basal levels of S845 phospho-GluA1 (P-GluA1)
      and cell surface GluA1 in the NAc following protracted withdrawal from cocaine
      exposure, changes that occur independently of LTCCs. In contrast, we found that a
      cocaine challenge that elicits expression of the cocaine-sensitized response
      increases S831 P-GluA1 that further increases surface GluA1 beyond the higher
      basal levels. Intra-NAc pharmacological manipulations indicate that the Ca(v)1.2
      activated CaM kinase II (CaMKII) mediates cocaine-induced increase in S831 P
      GluA1 and that both Ca(v)1.2-activated CaMKII and extracellular signal-regulated
      kinase 2 (ERK2) mediate the increase in GluA1 cell surface levels specific to the
      sensitized response. Experiments using adenoassociated viral vectors expressing
      Ca(v)1.3 and ERK2 siRNA further indicate that recruitment of the Ca(v)1.2 pathway
      in the NAc is dependent on ventral tegmental area Ca(v)1.3 LTCCs and ERK2.
      Together, these results identify candidate pathways that mediate cocaine-induced
      AMPAR plasticity in the NAc and provide a mechanism linking LTCCs and GluA1
      plasticity to cocaine-induced persistent behavioral changes.

PMID- 21940449
TI  - Focal adhesion kinase promotes integrin adhesion dynamics necessary for
      chemotropic turning of nerve growth cones.
AB  - The ability of extending axons to navigate using combinations of extracellular
      cues is essential for proper neural network formation. One intracellular
      signaling molecule that integrates convergent signals from both extracellular
      matrix (ECM) proteins and growth factors is focal adhesion kinase (FAK). Analysis
      of FAK function shows that it influences a variety of cellular activities,
      including cell motility, proliferation, and differentiation. Recent work in
      developing neurons has shown that FAK and Src function downstream of both
      attractive and repulsive growth factors, but little is known about the effectors
      or cellular mechanisms that FAK controls in growth cones on ECM proteins. We
      report that FAK functions downstream of brain-derived neurotrophic factor (BDNF)
      and laminin in the modulation of point contact dynamics, phosphotyrosine
      signaling at filopodial tips, and lamellipodial protrusion. BDNF stimulation
      accelerates paxillin-containing point contact turnover and formation. Knockdown
      of FAK function either with a FAK antisense morpholino or by expression of FRNK,
      a dominant-negative FAK isoform, blocks all aspects of the response to BDNF,
      including the acceleration of point contact dynamics. On the other hand,
      expression of specific FAK point mutants can selectively disrupt distinct aspects
      of the response to BDNF. We also show that growth cone turning depends on both
      signaling cascades tested here. Finally, we provide the first evidence that
      growth cone point contacts are asymmetrically regulated during turning to an
      attractive guidance cue.

PMID- 21940451
TI  - The relationship between cortical magnification factor and population receptive
      field size in human visual cortex: constancies in cortical architecture.
AB  - Receptive field (RF) sizes and cortical magnification factor (CMF) are
      fundamental organization properties of the visual cortex. At increasing visual
      eccentricity, RF sizes increase and CMF decreases. A relationship between RF size
      and CMF suggests constancies in cortical architecture, as their product, the
      cortical representation of an RF (point image), may be constant. Previous animal
      neurophysiology studies of this question yield conflicting results. Here, we use
      fMRI to determine the relationship between the population RF (pRF) and CMF in
      humans. In average and individual data, the product of CMF and pRF size, the
      population point image, is near constant, decreasing slightly with eccentricity
      in V1. Interhemisphere and subject variations in CMF, pRF size, and V1 surface
      area are correlated, and the population point image varies less than these
      properties. These results suggest a V1 cortical processing architecture of
      approximately constant size between humans. Up the visual hierarchy, to V2, V3,
      hV4, and LO1, the population point image decreases with eccentricity, and both
      the absolute values and rate of change increase. PRF sizes increase between
      visual areas and with eccentricity, but when expressed in V1 cortical surface
      area (i.e., corticocortical pRFs), they are constant across eccentricity in
      V2/V3. Thus, V2/V3, and to some degree hV4, sample from a constant extent of V1.
      This may explain population point image changes in later areas. Consequently, the
      constant factor determining pRF size may not be the relationship to the local
      CMF, but rather pRF sizes and CMFs in visual areas from which the pRF samples.

PMID- 21940450
TI  - Relief of Mg2+-dependent inhibition of TRPM1 by PKCalpha at the rod bipolar cell
      synapse.
AB  - In the retina, light onset hyperpolarizes photoreceptors and depolarizes ON
      bipolar cells at the sign inverting photoreceptor-ON bipolar cell synapse.
      Transmission at this synapse is mediated by a signaling cascade comprised of
      mGluR6, a G-protein containing G(alphao), and the cation channel TRP melastatin 1
      (TRPM1). This system is thought to be common to both the rod- and ON-cone-driven
      pathways, which control vision under scotopic and photopic conditions,
      respectively. In this study, we present evidence that the rod pathway is uniquely
      susceptible to modulation by PKCalpha at the rod-rod bipolar cell synapse.
      Decreased production of DAG (an activator of PKC) by inhibition of PIP2
      (phosphatidylinositol-4,5-bisphosphate) hydrolysis caused depression of the TRPM1
      current. Conversely, addition of a DAG analog, 2-acetyl-1-oleoyl-sn-glycerol
      (OAG), potentiated the current in rod bipolar cells but not in ON-cone bipolar
      cells. The potentiating effects of OAG were absent both in mutant mice that lack
      PKCalpha expression and in wild-type mice in which enzymatic activity of PKCalpha
      was pharmacologically inhibited. In addition, we found that, like other members
      of the TRPM subfamily, TRPM1 current is susceptible to voltage-independent
      inhibition by intracellular magnesium, and that modulation by PKCalpha relieves
      this inhibition, as the potentiating effects of OAG are absent in low
      intracellular magnesium. We conclude that activation of PKCalpha initiates a
      modulatory mechanism at the rod-rod bipolar cell synapse whose function is to
      reduce inhibition of the TRPM1 current by magnesium, thereby increasing the gain
      of transmission at this synapse.

PMID- 21940452
TI  - Cdk5-mediated phosphorylation of Axin directs axon formation during cerebral
      cortex development.
AB  - Axon formation is critical for the establishment of connections between neurons,
      which is a prerequisite for the development of neural circuitry. Kinases such as
      cyclin-dependent kinase 5 (Cdk5) and glycogen synthase kinase-3beta (GSK-3beta),
      have been implicated to regulate axon outgrowth. Nonetheless, the in vivo roles
      of these kinases in axon development and the underlying signaling mechanisms
      remain essentially unknown. We report here that Cdk5 is important for axon
      formation in mouse cerebral cortex through regulating the functions of axis
      inhibitor (Axin), a scaffold protein of the canonical Wnt pathway. Knockdown of
      Axin in utero abolishes the formation and projection of axons. Importantly, Axin
      is phosphorylated by Cdk5, and this phosphorylation facilitates the interaction
      of Axin with GSK-3beta, resulting in inhibition of GSK-3beta activity and
      dephosphorylation of its substrate collapsin response mediator protein-2 (CRMP
      2), a microtubule-associated protein. Specifically, both phosphorylation of Axin
      and its interaction with GSK-3beta are critically required for axon formation in
      mouse cortex development. Together, our findings reveal a new regulatory
      mechanism of axon formation through Cdk5-dependent phosphorylation of Axin.

PMID- 21940453
TI  - Forebrain CRF1 modulates early-life stress-programmed cognitive deficits.
AB  - Childhood traumatic events hamper the development of the hippocampus and impair
      declarative memory in susceptible individuals. Persistent elevations of
      hippocampal corticotropin-releasing factor (CRF), acting through CRF receptor 1
      (CRF1), in experimental models of early-life stress have suggested a role for
      this endogenous stress hormone in the resulting structural modifications and
      cognitive dysfunction. However, direct testing of this possibility has been
      difficult. In the current study, we subjected conditional forebrain CRF1 knock
      out (CRF1-CKO) mice to an impoverished postnatal environment and examined the
      role of forebrain CRF1 in the long-lasting effects of early-life stress on
      learning and memory. Early-life stress impaired spatial learning and memory in
      wild-type mice, and postnatal forebrain CRF overexpression reproduced these
      deleterious effects. Cognitive deficits in stressed wild-type mice were
      associated with disrupted long-term potentiation (LTP) and a reduced number of
      dendritic spines in area CA3 but not in CA1. Forebrain CRF1 deficiency restored
      cognitive function, LTP and spine density in area CA3, and augmented CA1 LTP and
      spine density in stressed mice. In addition, early-life stress differentially
      regulated the amount of hippocampal excitatory and inhibitory synapses in wild
      type and CRF1-CKO mice, accompanied by alterations in the neurexin-neuroligin
      complex. These data suggest that the functional, structural and molecular changes
      evoked by early-life stress are at least partly dependent on persistent forebrain
      CRF1 signaling, providing a molecular target for the prevention of cognitive
      deficits in adults with a history of early-life adversity.

PMID- 21940454
TI  - Supramodal representation of emotions.
AB  - Supramodal representation of emotion and its neural substrates have recently
      attracted attention as a marker of social cognition. However, the question
      whether perceptual integration of facial and vocal emotions takes place in
      primary sensory areas, multimodal cortices, or in affective structures remains
      unanswered yet. Using novel computer-generated stimuli, we combined emotional
      faces and voices in congruent and incongruent ways and assessed functional brain
      data (fMRI) during an emotional classification task. Both congruent and
      incongruent audiovisual stimuli evoked larger responses in thalamus and superior
      temporal regions compared with unimodal conditions. Congruent emotions were
      characterized by activation in amygdala, insula, ventral posterior cingulate
      (vPCC), temporo-occipital, and auditory cortices; incongruent emotions activated
      a frontoparietal network and bilateral caudate nucleus, indicating a greater
      processing load in working memory and emotion-encoding areas. The vPCC alone
      exhibited differential reactions to congruency and incongruency for all emotion
      categories and can thus be considered a central structure for supramodal
      representation of complex emotional information. Moreover, the left amygdala
      reflected supramodal representation of happy stimuli. These findings document
      that emotional information does not merge at the perceptual audiovisual
      integration level in unimodal or multimodal areas, but in vPCC and amygdala.

PMID- 21940455
TI  - Differentially organized top-down modulation of prepulse inhibition of startle.
AB  - Prepulse inhibition (PPI) of startle is the suppression of the startle reflex
      when a weaker sensory stimulus (the prepulse) shortly precedes the startling
      stimulus. PPI can be attentionally enhanced in both humans and laboratory
      animals. This study investigated whether the following three forebrain
      structures, which are critical for initial cortical processing of auditory
      signals, auditory fear conditioning/memories, and spatial attention,
      respectively, play a role in the top-down modulation of PPI in rats: the primary
      auditory cortex (A1), lateral nucleus of the amygdala (LA), and posterior
      parietal cortex (PPC). The results show that, under the noise-masking condition,
      PPI was enhanced by fear conditioning of the prepulse in a prepulse-specific
      manner, and the conditioning-induced PPI enhancement was further increased by
      perceptual separation between the conditioned prepulse and the noise masker.
      Reversibly blocking glutamate receptors in the A1 with 2 mm kynurenic acid
      eliminated both the conditioning-induced and perceptual separation-induced PPI
      enhancements. Blocking the LA eliminated the conditioning-induced but not the
      perceptual separation-induced PPI enhancement, and blocking the PPC specifically
      eliminated the perceptual separation-induced PPI enhancement. The two types of
      PPI enhancements were also eliminated by the extinction manipulation. Thus, the
      top-down modulation of PPI is differentially organized and depends on operations
      of various forebrain structures. Due to the fine-tuned modulation by higher-order
      cognitive processes, functions of PPI can be more flexible to complex
      environments. The top-down enhancements of PPI in rats are also useful for
      modeling some mental disorders, such as schizophrenia, attention
      deficit/hyperactivity disorder, and posttraumatic stress disorder.

PMID- 21940456
TI  - Knocking out P2X receptors reduces transmitter secretion in taste buds.
AB  - In response to gustatory stimulation, taste bud cells release a transmitter, ATP,
      that activates P2X2 and P2X3 receptors on gustatory afferent fibers. Taste
      behavior and gustatory neural responses are largely abolished in mice lacking
      P2X2 and P2X3 receptors [P2X2 and P2X3 double knock-out (DKO) mice]. The
      assumption has been that eliminating P2X2 and P2X3 receptors only removes
      postsynaptic targets but that transmitter secretion in mice is normal. Using
      functional imaging, ATP biosensor cells, and a cell-free assay for ATP, we tested
      this assumption. Surprisingly, although gustatory stimulation mobilizes Ca(2+) in
      taste Receptor (Type II) cells from DKO mice, as from wild-type (WT) mice, taste
      cells from DKO mice fail to release ATP when stimulated with tastants. ATP
      release could be elicited by depolarizing DKO Receptor cells with KCl, suggesting
      that ATP-release machinery remains functional in DKO taste buds. To explore the
      difference in ATP release across genotypes, we used reverse transcriptase (RT)
      PCR, immunostaining, and histochemistry for key proteins underlying ATP secretion
      and degradation: Pannexin1, TRPM5, and NTPDase2 (ecto-ATPase) are
      indistinguishable between WT and DKO mice. The ultrastructure of contacts between
      taste cells and nerve fibers is also normal in the DKO mice. Finally,
      quantitative RT-PCR show that P2X4 and P2X7, potential modulators of ATP
      secretion, are similarly expressed in taste buds in WT and DKO taste buds.
      Importantly, we find that P2X2 is expressed in WT taste buds and appears to
      function as an autocrine, positive feedback signal to amplify taste-evoked ATP
      secretion.

PMID- 21940457
TI  - Reorganization of somatosensory cortical areas 3b and 1 after unilateral section
      of dorsal columns of the spinal cord in squirrel monkeys.
AB  - An incomplete lesion of the ascending afferents from the hand in the dorsal
      columns of the spinal cord in monkeys is followed after weeks of recovery by a
      reactivation of much of the territory of the hand representations in primary
      somatosensory cortex (area 3b). However, the relationship between the extent of
      the dorsal column lesion and the amount of cortical reactivation has not been
      clear. Largely, this is due to the uncertainties about axon sparing after spinal
      cord lesions. Here, we unilaterally sectioned dorsal column afferents in the
      cervical spinal cord (C4-C6) in adult squirrel monkeys. After weeks of recovery,
      cholera toxin subunit B (CTB) was injected into the distal phalanges to label
      normal and surviving afferents to the cuneate nuclei representing the hands. Days
      later, the responsiveness of neurons in cortical areas 3b and 1 to tactile
      stimulation on the hand was evaluated in a microelectrode mapping session. The
      sizes and densities of CTB-labeled patches in the cuneate nuclei of both sides
      were quantified and compared. The results indicate that extensive reactivations
      of the hand representations in cortical areas 3b and 1 occur contralateral to the
      spinal cord lesion, even when <1% of labeled dorsal column terminations in the
      cuneate nucleus remained. These results raise the possibilities that secondary
      afferents from innervated neurons in the spinal cord contribute to the
      reactivation, and that the reactivation of area 1 is not completely dependent on
      inputs from area 3b.

PMID- 21940458
TI  - "Overshoot" of O2 is required to maintain baseline tissue oxygenation at
      locations distal to blood vessels.
AB  - In vivo imaging of cerebral tissue oxygenation is important in defining healthy
      physiology and pathological departures associated with cerebral disease. We used
      a recently developed two-photon microscopy method, based on a novel
      phosphorescent nanoprobe, to image tissue oxygenation in the rat primary sensory
      cortex in response to sensory stimulation. Our measurements showed that a
      stimulus-evoked increase in tissue pO2 depended on the baseline pO2 level. In
      particular, during sustained stimulation, the steady-state pO2 at low-baseline
      locations remained at the baseline, despite large pO2 increases elsewhere. In
      contrast to the steady state, where pO2 never decreased below the baseline,
      transient decreases occurred during the "initial dip" and "poststimulus
      undershoot." These results suggest that the increase in blood oxygenation during
      the hemodynamic response, which has been perceived as a paradox, may serve to
      prevent a sustained oxygenation drop at tissue locations that are remote from the
      vascular feeding sources.

PMID- 21940460
TI  - Process and outcome constructs for evaluating community-based participatory
      research projects: a matrix of existing measures.
AB  - Community-based participatory research (CBPR) has been widely used in public
      health research in the last decade as an approach to develop culturally centered
      interventions and collaborative research processes in which communities are
      directly involved in the construction and implementation of these interventions
      and in other application of findings. Little is known, however, about CBPR
      pathways of change and how these academic-community collaborations may contribute
      to successful outcomes. A new health CBPR conceptual model (Wallerstein N, Oetzel
      JG, Duran B et al. CBPR: What predicts outcomes? In: Minkler M, Wallerstein N
      (eds). Communication Based Participatory Research, 2nd edn. San Francisco, CA:
      John Wiley & Co., 2008) suggests that relationships between four components:
      context, group dynamics, the extent of community-centeredness in intervention
      and/or research design and the impact of these participatory processes on CBPR
      system change and health outcomes. This article seeks to identify instruments and
      measures in a comprehensive literature review that relates to these distinct
      components of the CBPR model and to present them in an organized and indexed
      format for researcher use. Specifically, 258 articles were identified in a review
      of CBPR (and related) literature from 2002 to 2008. Based on this review and from
      recommendations of a national advisory board, 46 CBPR instruments were identified
      and each was reviewed and coded using the CBPR logic model. The 46 instruments
      yielded 224 individual measures of characteristics in the CBPR model. While this
      study does not investigate the quality of the instruments, it does provide
      information about reliability and validity for specific measures. Group dynamics
      proved to have the largest number of identified measures, while context and CBPR
      system and health outcomes had the least. Consistent with other summaries of
      instruments, such as Granner and Sharpe's inventory (Granner ML, Sharpe PA.
      Evaluating community coalition characteristics and functioning: a summary of
      measurement tools. Health Educ Res 2004; 19: 514-32), validity and reliability
      information were often lacking, and one or both were only available for 65 of the
      224 measures. This summary of measures provides a place to start for new and
      continuing partnerships seeking to evaluate their progress.

PMID- 21940459
TI  - Surface traffic of dendritic CaV1.2 calcium channels in hippocampal neurons.
AB  - In neurons L-type calcium currents function in gene regulation and synaptic
      plasticity, while excessive calcium influx leads to excitotoxicity and
      neurodegeneration. The major neuronal Ca(V)1.2 L-type channels are localized in
      clusters in dendritic shafts and spines. Whereas Ca(V)1.2 clusters remain stable
      during NMDA-induced synaptic depression, L-type calcium currents are rapidly
      downregulated during strong excitatory stimulation. Here we used fluorescence
      recovery after photobleaching (FRAP), live cell-labeling protocols, and single
      particle tracking (SPT) to analyze the turnover and surface traffic of Ca(V)1.2
      in dendrites of mature cultured mouse and rat hippocampal neurons, respectively.
      FRAP analysis of channels extracellularly tagged with superecliptic pHluorin
      (Ca(V)1.2-SEP) demonstrated ~20% recovery within 2 min without reappearance of
      clusters. Pulse-chase labeling showed that membrane-expressed Ca(V)1.2-HA is not
      internalized within1 h, while blocking dynamin-dependent endocytosis resulted in
      increased cluster density after 30 min. Together, these results suggest a
      turnover rate of clustered Ca(V)1.2s on the hour time scale. Direct recording of
      the lateral movement in the membrane using SPT demonstrated that dendritic
      Ca(V)1.2s show highly confined mobility with diffusion coefficients of ~0.005
      MUm2 s-1. Consistent with the mobile Ca(V)1.2 fraction observed in FRAP, a ~30%
      subpopulation of channels reversibly exchanged between confined and diffusive
      states. Remarkably, high potassium depolarization did not alter the recovery
      rates in FRAP or the diffusion coefficients in SPT analyses. Thus, an equilibrium
      of clustered and dynamic Ca(V)1.2s maintains stable calcium channel complexes
      involved in activity-dependent cell signaling, whereas the minor mobile channel
      pool in mature neurons allows limited capacity for short-term adaptations.

PMID- 21940461
TI  - Reading comprehension and expressive writing: a comparison between good and poor
      comprehenders.
AB  - This study investigated expressive writing in 8- to 10-year-old children with
      different levels of reading comprehension. Poor and good comprehenders were
      presented with three expressive writing tasks where the modality (pictorial vs.
      verbal) and the text genre (narrative vs. descriptive) varied. Results showed
      that poor comprehenders' performance was minimally influenced by the modality of
      the prompt. In fact, their performance was generally worse than that of good
      comprehenders and affected by the text genre, as the quality of their narratives
      was generally lower than that of good comprehenders. However, in the descriptive
      text condition, their performance was comparable to that of good comprehenders.
      One can conclude that their problems depend on the characteristics of the
      narrative text where coherence and causality are important elements.

PMID- 21940462
TI  - The effects and interactions of student, teacher, and setting variables on
      reading outcomes for kindergartners receiving supplemental reading intervention.
AB  - This exploratory study examined the influences of student, teacher, and setting
      characteristics on kindergarteners' early reading outcomes and investigated
      whether those relations were moderated by type of intervention. Participants
      included 206 kindergarteners identified as at risk for reading difficulties and
      randomly assigned to one of two supplemental interventions: (a) an experimental
      explicit, systematic, code-based program or (b) their schools' typical
      kindergarten reading intervention. Results from separate multilevel structural
      equation models indicated that among student variables, entry-level alphabet
      knowledge was positively associated with phonemic and decoding outcomes in both
      conditions. Entry-level rapid automatized naming also positively influenced
      decoding outcomes in both conditions. However, its effect on phonemic outcomes
      was statistically significant only among children in the typical practice
      comparison condition. Regarding teacher variables, the quality of instruction was
      associated with significantly higher decoding outcomes in the typical reading
      intervention condition but had no statistically significant influence on phonemic
      outcomes in either condition. Among setting variables, instruction in smaller
      group sizes was associated with better phonemic outcomes in the comparison
      condition but had no statistically significant influence on outcomes of children
      in the intervention group. Mode of delivery (i.e., pullout vs. in class) had no
      statistically significant influence on either outcome variable.

PMID- 21940463
TI  - Examining the role of attention and instruction in at-risk kindergarteners:
      electrophysiological measures of selective auditory attention before and after an
      early literacy intervention.
AB  - Several studies report that adults and adolescents with reading disabilities also
      experience difficulties with selective attention. In the present study, event
      related brain potentials (ERPs) were used to examine the neural mechanisms of
      selective attention in kindergarten children at risk for reading disabilities (AR
      group, n = 8) or on track in early literacy skills (OT group, n = 6) across the
      first semester of kindergarten. The AR group also received supplemental
      instruction with the Early Reading Intervention (ERI). Following ERI, the AR
      group demonstrated improved skills on standardized early literacy measures such
      that there were no significant differences between the AR and OT groups at
      posttest or winter follow-up. Analysis of the ERP data revealed that at the start
      of kindergarten, the AR group displayed reduced effects of attention on
      sensorineural processing compared to the OT group. Following intervention, this
      difference between groups disappeared, with the AR group only showing
      improvements in the effect of attention on sensorineural processing. These data
      indicate that the neural mechanisms of selective attention are atypical in
      kindergarten children at risk for reading failure but can be improved by
      effective reading interventions.

PMID- 21940464
TI  - Novel multitarget real-time PCR assay for rapid detection of Bordetella species
      in clinical specimens.
AB  - A novel multitarget real-time PCR (RT-PCR) assay for the rapid identification of
      Bordetella pertussis, B. parapertussis, and B. holmesii was developed using
      multicopy insertion sequences (ISs) in combination with the pertussis toxin
      subunit S1 (ptxS1) singleplex assay. The RT-PCR targets for the multiplex assay
      include IS481, commonly found in B. pertussis and B. holmesii; IS1001 of B.
      parapertussis; and the IS1001-like sequence of B. holmesii. Overall, 402
      Bordetella species and 66 non-Bordetella species isolates were tested in the
      multitarget assay. Cross-reactivity was found only with 5 B. bronchiseptica
      isolates, which were positive with IS1001 of B. parapertussis. The lower limit of
      detection (LLOD) of the multiplex assay was similar to the LLOD of each target in
      an individual assay format, which was approximately 1 genomic equivalent per
      reaction for all targets. A total of 197 human clinical specimens obtained during
      cough-illness outbreak investigations were used to evaluate the multitarget RT
      PCR assay. The multiplex assay results from 87 clinical specimens were compared
      to the individual RT-PCR assay and culture results. The multitarget assay is
      useful as a diagnostic tool to confirm B. pertussis infections and to rapidly
      identify other Bordetella species. In conclusion, the use of this multitarget RT
      PCR approach increases specificity, while it decreases the amount of time,
      reagents, and specimen necessary for RT-PCRs used for accurate diagnosis of
      pertussis-like illness.

PMID- 21940465
TI  - DNA microarray genotyping and virulence and antimicrobial resistance gene
      profiling of methicillin-resistant Staphylococcus aureus bloodstream isolates
      from renal patients.
AB  - Thirty-six methicillin-resistant Staphylococcus aureus (MRSA) bloodstream
      isolates from renal patients were genetically characterized by DNA microarray
      analysis and spa typing. The isolates were highly clonal, belonging mainly to
      ST22-MRSA-IV. The immune evasion and enterotoxin gene clusters were found in
      29/36 (80%) and 33/36 (92%) isolates, respectively.

PMID- 21940466
TI  - Comparison of a newly developed automated and quantitative hepatitis C virus
      (HCV) core antigen test with the HCV RNA assay for clinical usefulness in
      confirming anti-HCV results.
AB  - Hepatitis C virus (HCV) is a global health care problem. Diagnosis of HCV
      infection is mainly based on the detection of anti-HCV antibodies as a screening
      test with serum samples. Recombinant immunoblot assays are used as supplemental
      tests and for the final detection and quantification of HCV RNA in confirmatory
      tests. In this study, we aimed to compare the HCV core antigen test with the HCV
      RNA assay for confirming anti-HCV results to determine whether the HCV core
      antigen test may be used as an alternative confirmatory test to the HCV RNA test
      and to assess the diagnostic values of the total HCV core antigen test by
      determining the diagnostic specificity and sensitivity rates compared with the
      HCV RNA test. Sera from a total of 212 treatment-naive patients were analyzed for
      anti-HCV and HCV core antigen both with the Abbott Architect test and with the
      molecular HCV RNA assay consisting of a reverse transcription-PCR method as a
      confirmatory test. The diagnostic sensitivity, specificity, and positive and
      negative predictive values of the HCV core antigen assay compared to the HCV RNA
      test were 96.3%, 100%, 100%, and 89.7%, respectively. The levels of HCV core
      antigen showed a good correlation with those from the HCV RNA quantification (r =
      0.907). In conclusion, the Architect HCV antigen assay is highly specific,
      sensitive, reliable, easy to perform, reproducible, cost-effective, and
      applicable as a screening, supplemental, and preconfirmatory test for anti-HCV
      assays used in laboratory procedures for the diagnosis of hepatitis C virus
      infection.

PMID- 21940467
TI  - Characterization of microevolution events in Mycobacterium tuberculosis strains
      involved in recent transmission clusters.
AB  - Under certain circumstances, it is possible to identify clonal variants of
      Mycobacterium tuberculosis infecting a single patient, probably as a result of
      subtle genetic rearrangements in part of the bacillary population. We
      systematically searched for these microevolution events in a different context,
      namely, recent transmission chains. We studied the clustered cases identified
      using a population-based universal molecular epidemiology strategy over a 5-year
      period. Clonal variants of the reference strain defining the cluster were found
      in 9 (12%) of the 74 clusters identified after the genotyping of 612 M.
      tuberculosis isolates by IS6110 restriction fragment length polymorphism analysis
      and mycobacterial interspersed repetitive units-variable-number tandem repeat
      typing. Clusters with microevolution events were epidemiologically supported and
      involved 4 to 9 cases diagnosed over a 1- to 5-year period. The IS6110 insertion
      sites from 16 representative isolates of reference and microevolved variants were
      mapped by ligation-mediated PCR in order to characterize the genetic background
      involved in microevolution. Both intragenic and intergenic IS6110 locations
      resulted from these microevolution events. Among those cases of IS6110 locations
      in intergenic regions which could have an effect on the regulation of adjacent
      genes, we identified the overexpression of cytochrome P450 in one microevolved
      variant using quantitative real-time reverse transcription-PCR. Our results help
      to define the frequency with which microevolution can be expected in M.
      tuberculosis transmission chains. They provide a snapshot of the genetic
      background of these subtle rearrangements and identify an event in which IS6110
      mediated microevolution in an isogenic background has functional consequences.

PMID- 21940468
TI  - Target-specific capture enhances sensitivity of electrochemical detection of
      bacterial pathogens.
AB  - We report the concentration and purification of bacterial 16S rRNA by the use of
      a biotinylated DNA target-specific capture (TSC) probe. For both cultivated
      bacterial and urine specimens from urinary tract infection patients, TSC resulted
      in a 5- to 8-fold improvement in the sensitivity of bacterial detection in a 16S
      rRNA electrochemical sensor assay.

PMID- 21940470
TI  - Prevalence of shiga toxin-producing Escherichia coli as detected by enzyme-linked
      immunoassays and real-time PCR during the summer months in northern Alberta,
      Canada.
AB  - Shiga toxin-producing Escherichia coli (STEC) in northern Alberta was detected
      using two enzyme immunoassays and an in-house real-time PCR. Of 2,328 stool
      samples, 8 were positive for O157:H7 STEC and 13 were positive for non-O157 STEC.
      No significant gender (P = 0.17) or age (P = 0.81) differences between groups
      were seen. Most positive diarrheal stool samples were nonbloody.

PMID- 21940471
TI  - Generic microtiter plate assay for triaging clinical specimens prior to
      genotyping of human papillomavirus DNA via consensus PCR.
AB  - A generic human papillomavirus (HPV) probe assay was compared to the Linear Array
      to detect HPV DNA in 1,013 clinical specimens. The sensitivity, specificity, and
      negative predictive value of the assay were 99.5% (95% confidence interval [CI],
      98.4% to 99.9%), 58.6% (95% CI, 53.9% to 63.1%), and 98.9% (95% CI, 96.5% to
      99.8%), respectively. This assay conveniently identifies HPV-positive specimens.

PMID- 21940472
TI  - Aortic homograft endocarditis caused by Campylobacter jejuni.
AB  - We report the first case of homograft endocarditis caused by Campylobacter
      jejuni, which was treated successfully with antibiotic therapy and valve
      replacement. To our knowledge, only two other cases of C. jejuni endocarditis,
      involving native valves, have been reported in the medical literature.

PMID- 21940473
TI  - Type-specific human papillomavirus E6/E7 mRNA detection by real-time PCR improves
      identification of cervical neoplasia.
AB  - DNA-based human papillomavirus (HPV) assays show high sensitivity but poor
      specificity in detecting high-grade cervical lesions. Assays detecting mRNA of
      the oncoproteins E6 and E7 show higher specificity but lack either detection of
      all high-risk HPV genotypes or the capacity to specify the detected genotypes.
      Therefore, a real-time PCR assay detecting type-specific E6/E7 mRNA was developed
      and the clinical performance evaluated. A total of 210 cervical LBC (liquid-based
      cytology) samples from 204 women were analyzed for HPV DNA and mRNA with the in
      house real-time PCR as well as PreTect HPV-Proofer. The sensitivity of real-time
      PCR mRNA detection to identify histologically confirmed CIN2+ (cervical
      intraepithelial neoplasia, grade 2 or higher) was 0.91, compared to 0.95 for DNA
      analysis. The specificity was 0.68 compared to 0.38, and the positive predictive
      value (PPV) was higher for mRNA (0.67 versus 0.52) without any loss in negative
      predictive value (NPV). The sensitivity of the real-time PCR mRNA test was
      somewhat higher than that for PreTect HPV-Proofer (0.83 versus 0.75) in analyses
      for the same genotypes. The specificities were similar (0.76 versus 0.77). In
      analyses for mRNA of the eight most common genotypes in cervical cancer (HPV16, 
      18, -31, -33, -35, -45, -52, and -58), the sensitivity of detection of CIN2+
      lesions was 0.87 and the specificity 0.74, with a PPV of 0.70. In conclusion,
      real-time PCR for detection of HPV E6/E7 mRNA transcripts can be a sensitive and
      specific tool in screening and investigation of cervical neoplasia. The
      composition of HPV types in mRNA testing needs to be further investigated to
      optimize sensitivity and specificity.

PMID- 21940474
TI  - Species distribution of the Mycobacterium tuberculosis complex in clinical
      isolates from 2007 to 2010 in Turkey: a prospective study.
AB  - The Mycobacterium tuberculosis complex (MTBC) consists of a group of closely
      related species that differ in their epidemiological profiles, host ranges,
      pathogenicities, geographic distributions, and drug resistances. Identification
      of members in the MTBC is essential for monitoring the epidemiology of
      tuberculosis (TB) and implementing appropriate public health control measures. In
      this study, 188 consecutive MTBC clinical isolates from 2007 to 2010 were
      evaluated to determine the prevalence of MTBC species in Turkey. PCR and
      restriction fragment length polymorphism analysis (PCR-RFLP) of the gyrB gene
      were used, and results for species other than M. tuberculosis were confirmed
      using the GenoType MTBC assay (Hain Lifescience, Nehren, Germany). Most of the
      strains were found to be M. tuberculosis (94.1%). The prevalences of M. bovis and
      M. caprae were 4.3% and 1.6%, respectively. Only one M. bovis BCG strain was
      identified. Overall, the frequency of bovine tuberculosis in humans was 5.3%. We
      had assumed that bovine TB infection was under control in animal herds, but
      primary M. bovis infections in humans caused by transmission from infected
      animals are still an issue in Turkey. Our results indicate that the frequent
      identification of M. bovis in routine mycobacteriological laboratory work has
      further importance due to the well-known resistance of this species to
      pyrazinamide.

PMID- 21940475
TI  - Molecular testing for Trichomonas vaginalis in women: results from a prospective
      U.S. clinical trial.
AB  - Trichomoniasis is a common sexually transmitted disease associated with preterm
      birth, low birth weight, and increased susceptibility to infection with other
      pathogenic sexually transmitted microorganisms. Nucleic acid amplification tests
      for Trichomonas vaginalis have improved sensitivity for detecting infected
      individuals compared to existing culture-based methods. This prospective,
      multicenter U.S. clinical trial evaluated the performance of the automated Aptima
      T. vaginalis assay for detecting T. vaginalis in 1,025 asymptomatic and
      symptomatic women. Vaginal swab, endocervical swab, ThinPrep PreservCyt, and
      urine specimens were collected. Subject infection status was determined by wet
      mount microscopy and culture. Aptima T. vaginalis assay performance was
      determined for each specimen type by comparison to subject infection status. Of
      933 subjects analyzed, 59.9% were symptomatic. Aptima T. vaginalis clinical
      sensitivity and specificity were, respectively, 100% and 99.0% for vaginal swabs,
      100% and 99.4% for endocervical swabs, 100% and 99.6% in ThinPrep samples, and
      95.2% and 98.9% in urine specimens. Aptima T. vaginalis performance levels were
      similar in asymptomatic and symptomatic subjects. This study validates the
      clinical performance of the Aptima T. vaginalis assay for screening asymptomatic
      and symptomatic women for T. vaginalis infection.

PMID- 21940476
TI  - Molecular epidemiology of Clostridium difficile strains in children compared with
      that of strains circulating in adults with Clostridium difficile-associated
      infection.
AB  - Molecular analysis of Clostridium difficile (28 isolates) from children (n = 128)
      in Oxfordshire, United Kingdom, identified eight toxigenic genotypes. Six of
      these were isolated from 27% of concurrent adult C. difficile-associated
      infections studied (n = 83). No children carried hypervirulent PCR ribotype 027.
      Children could participate in the transmission of some adult disease-causing
      genotypes.

PMID- 21940477
TI  - SmaI restriction site-based multiplex PCR for typing of hospital- and community
      acquired Staphylococcus aureus.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is an important nosocomial
      pathogen, and morbidity and mortality rates associated with this pathogen have
      increased markedly in recent years. MRSA strains are generally resistant to
      several classes of antibiotics and are therefore difficult and costly to treat. A
      major issue is to identify the sources of MRSA infections and to monitor their
      epidemic spread. In this study, we report the development of a typing technique
      for S. aureus, based on single-nucleotide polymorphism (SNP) variations in and
      around SmaI-restriction sites (CCCGGG). An assessment of the SmaI restriction
      site-based multiplex PCR (SmaI-multiplex PCR) typing (SMT) with respect to pulsed
      field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) revealed a
      high level of concordance in the clustering of the test strains. The SmaI
      multiplex PCR was found to be more discriminatory than MLST/staphylococcal
      cassette chromosome mec (SCCmec) typing but less discriminatory than PFGE. SMT
      can provide real-time information for the investigation of ongoing S. aureus
      hospital outbreaks. SMT meets the criteria of a practical typing method: it is
      simple, reproducible, and highly discriminatory and does not require expensive
      equipment or specialist expertise. Consequently, SmaI-multiplex PCR has the
      potential to be used in routine clinical microbiology laboratories.

PMID- 21940478
TI  - Epidemic methicillin-susceptible Staphylococcus aureus lineages are the main
      cause of infections at an Iranian university hospital.
AB  - The majority of Staphylococcus aureus infections from Isfahan, Iran, were caused
      by epidemic methicillin-susceptible S. aureus (MSSA) lineages, sequence type 8
      (ST8), ST22, ST30, and ST6. The predominant methicillin-resistant S. aureus
      strain was ST239. We observed a high prevalence of Panton-Valentine leukocidin
      positive MSSA strains (19.7%), which is a matter of considerable concern, since
      these strains have the ability to cause severe infections.

PMID- 21940479
TI  - Evaluation of Aspergillus PCR protocols for testing serum specimens.
AB  - A panel of human serum samples spiked with various amounts of Aspergillus
      fumigatus genomic DNA was distributed to 23 centers within the European
      Aspergillus PCR Initiative to determine analytical performance of PCR.
      Information regarding specific methodological components and PCR performance was
      requested. The information provided was made anonymous, and meta-regression
      analysis was performed to determine any procedural factors that significantly
      altered PCR performance. Ninety-seven percent of protocols were able to detect a
      threshold of 10 genomes/ml on at least one occasion, with 83% of protocols
      reproducibly detecting this concentration. Sensitivity and specificity were 86.1%
      and 93.6%, respectively. Positive associations between sensitivity and the use of
      larger sample volumes, an internal control PCR, and PCR targeting the internal
      transcribed spacer (ITS) region were shown. Negative associations between
      sensitivity and the use of larger elution volumes (>=100 MUl) and PCR targeting
      the mitochondrial genes were demonstrated. Most Aspergillus PCR protocols used to
      test serum generate satisfactory analytical performance. Testing serum requires
      less standardization, and the specific recommendations shown in this article will
      only improve performance.

PMID- 21940480
TI  - Comparison of the INNO-LiPA and PapType assays for detection of human
      papillomavirus in archival vulva dysplasia and/or neoplasia tissue biopsy
      specimens.
AB  - INNO-LiPA and PapType human papillomavirus (HPV) genotyping assays were compared
      for detection of HPV genotypes on archival vulvar tissue. The INNO-LiPA assay
      detected 49 HPV-16 infections, compared with 47 detected by the PapType assay.
      The INNO-LiPA assay detected amplifiable DNA in 59 (91%) biopsy specimens,
      compared with 57 (88%) specimens for which amplifiable DNA was detected by the
      PapType assay. The two genotyping assays were highly comparable.

PMID- 21940481
TI  - Interpretation of serum PTH concentrations with different kits in dialysis
      patients according to the KDIGO guidelines: importance of the reference (normal)
      values.
AB  - BACKGROUND: The recommended target range for serum parathyroid hormone (PTH) in
      dialysis patients has changed from 150 to 300 pg/mL in the KDOQI guidelines to
      two to nine times the upper normal limit in the KDIGO ones. Although
      inclusion/exclusion criteria for the reference population are highly important,
      they are usually not mentioned in the commercial kits. In this study, we used the
      same reference population of vitamin D-replete normal subjects to establish
      reference values for 10 commercial PTH kits. We evaluated whether this may
      improve the classification of dialysis patients according to the KDIGO compared
      to the use of reference values proposed by the manufacturers. METHODS: We
      measured serum PTH with 10 different kits in 149 haemodialysis patients, and 240
      25-OH-vitamin D-replete (>75 nmol/L) individuals with an estimated glomerular
      filtration rate >60 mL/min/1.73 m(2). RESULTS: For the 10 kits, our upper normal
      limit was lower than those of the manufacturers. The difference was, however,
      variable from one kit to another. The two kits that yielded the lowest and the
      highest absolute concentrations classified differently 84/149 patients (56.4%)
      according to the KDOQI and 53/149 (36.2%) according to the KDIGO using the
      manufacturers' normal values. Using our normal values significantly decreased the
      discrepancies with 24/149 patients (16.1%) being still classified differently.
      Taking the measurement uncertainty into consideration, 8% of the patients only
      remained differently classified by these two kits. CONCLUSIONS: Using the same
      vitamin-D-replete population to establish the reference range for 10 commercial
      PTH kits significantly improved the classification of haemodialysis patients
      according to the KDIGO target range.

PMID- 21940482
TI  - Macrophage inhibitory cytokine-1 (MIC-1/GDF15) and mortality in end-stage renal
      disease.
AB  - BACKGROUND: Elevated macrophage inhibitory cytokine-1 (MIC-1/GDF15) levels in
      serum mediate anorexia and weight loss in some cancer patients and similarly
      elevated levels occur in chronic kidney disease (CKD). Serum MIC-1/GDF15 is also
      elevated in chronic inflammatory diseases and predicts atherosclerotic events
      independently of traditional risk factors. The relationship between chronic
      inflammation, decreasing body mass index (BMI) and increased mortality in CKD is
      not well understood and is being actively investigated. MIC-1/GDF15 may link
      these features of CKD. METHODS: Cohorts of incident dialysis patients from Sweden
      (n = 98) and prevalent hemodialysis patients from the USA (n = 381) had serum MIC
      1/GDF15, C-reactive protein (CRP) levels and BMI measured at study entry.
      Additional surrogate markers of nutritional adequacy, body composition and
      inflammation were assessed in Swedish patients. Patients were followed for all
      cause mortality. RESULTS: In the Swedish cohort, serum MIC-1/GDF15 was associated
      with decreasing BMI, measures of nutrition and markers of oxidative stress and
      inflammation. Additionally, high serum MIC-1/GDF15 levels identified patients
      with evidence of protein-energy wasting who died in the first 3 years of
      dialysis. The ability of serum MIC-1/GDF15 to predict mortality in the first 3
      years of dialysis was confirmed in the USA cohort. In both cohorts, serum MIC
      1/GDF15 level was an independent marker of mortality when adjusted for age, CRP,
      BMI, history of diabetes mellitus and/or cardiovascular disease and glomerular
      filtration rate or length of time on dialysis at study entry. CONCLUSIONS: MIC
      1/GDF15 is a novel independent serum marker of mortality in CKD capable of
      significantly improving the mortality prediction of other established markers.
      MIC-1/GDF15 may mediate protein-energy wasting in CKD and represent a novel
      therapeutic target for this fatal complication.

PMID- 21940483
TI  - Soluble interleukin-2 receptor alfa predicts renal outcome in IgA nephropathy.
AB  - BACKGROUND: Both systemic and mucosal IgA production are controlled by T
      lymphocytes and infiltrating T lymphocytes are involved in the progression of
      interstitial fibrosis in chronic kidney disease (CKD). Since the concentration of
      soluble interleukin-2 receptor alfa (sIL-2Ra) reflects the degree of T cell
      activation over time, we studied the impact of interleukin-2 receptor alfa levels
      on disease progression in patients with biopsy-proven IgA nephropathy (IgAN), a
      disease in which 20-30% of the patients progress to end-stage renal failure.
      METHODS: sIL-2Ra plasma levels were measured in 194 patients (median age 39
      years, 70% men) and 84 matched controls. One hundred and seventy-nine of the
      patients, with an estimated glomerular filtration rate (GFR) of >=15
      mL/min/1.73m(2) at baseline (CKD Stages 1-4), were followed for up to 15 years
      (median 52 months; range 12-188). sIL-2Ra was evaluated as a risk marker for
      severe renal progression, here defined by the development of CKD Stage 5 (GFR <15
      mL/min/1.73m(2)), a 50% decline in GFR during the follow-up period or a 30% GFR
      decline within 5 years of follow-up. In 51 patients, upon whom a renal biopsy had
      been performed within 2 years of IL2-Ra measurement, the biopsies were scored
      according to the Oxford classification. The correlations between the
      histopathological findings and the sIL-2Ra levels were examined. RESULTS: sIL2-Ra
      levels were significantly higher in patients than in controls (P < 0.001). sIL
      2Ra levels in the upper third tertile predicted a severe renal outcome, even
      after adjustment for the main clinical risk factors: time average albuminuria and
      GFR at baseline (Relative risk 5.35, P < 0.001). sIL-2Ra levels also correlated
      significantly to the yearly GFR slope (beta = -0.24, P = 0.01). According to the
      Oxford classification, the presence of >25% tubular atrophy/interstitial fibrosis
      (T1-2) was associated with higher sIL-2Ra levels, after adjustment for serum
      creatinine levels, if analysed within 4 months [n = 24, odds ratio (OR) 1.0, P =
      0.044] or within 2 years from the kidney biopsy (n = 51, OR 1.0, P = 0.017).
      CONCLUSIONS: The plasma levels of sIL-2Ra were predictive of long-term renal
      disease progression in a large cohort of patients with biopsy-proven IgAN.
      Further studies are warranted to evaluate if sIL-2Ra levels can feasibly
      contribute in the monitoring of effects of treatment, aimed to prevent the
      progression of interstitial fibrosis and progressive glomerulosclerosis in IgAN.

PMID- 21940484
TI  - Metabolic effects of dialyzate glucose in chronic hemodialysis: results from a
      prospective, randomized crossover trial.
AB  - BACKGROUND: There is no agreement concerning dialyzate glucose concentration in
      hemodialysis (HD) and 100 and 200 mg/dL (G100 and G200) are frequently used. G200
      may result in diffusive glucose flux into the patient, with consequent
      hyperglycemia and hyperinsulinism, and electrolyte alterations, in particular
      potassium (K) and phosphorus (P). This trial compared metabolic effects of G100
      versus G200. METHODS: Chronic HD patients participated in this randomized, single
      masked, controlled crossover trial (www.clinicaltrials.gov: #NCT00618033)
      consisting of two consecutive 3-week segments with G100 and G200, respectively.
      Intradialytic serum glucose (SG) and insulin concentrations (SI) were measured at
      0, 30, 60, 120, 180, 240 min and immediately post-HD; P and K were measured at 0,
      120, 180 min and post-HD. Hypoglycemia was defined as an SG<70 mg/dL. Mean SG and
      SI were computed as area under the curve divided by treatment time. RESULTS:
      Fourteen diabetic and 15 non-diabetic subjects were studied. SG was significantly
      higher with G200 as compared to G100, both in diabetic {G200: 192.8+/-48.1 mg/dL;
      G100: 154.0+/-27.3 mg/dL; difference 38.8 [95% confidence interval (CI): 21.2
      56.4] mg/dL; P<0.001} and non-diabetic subjects [G200: 127.0+/-11.2 mg/dL; G100
      106.5+/-10.8 mg/dL; difference 20.6 (95% CI: 15.3-25.9) mg/dL; P<0.001]. SI was
      significantly higher with G200 in non-diabetic subjects. Frequency of
      hypoglycemia, P and K serum levels, interdialytic weight gain and adverse
      intradialytic events did not differ significantly between G100 and G200.
      CONCLUSION: G200 may exert unfavorable metabolic effects in chronic HD patients,
      in particular hyperglycemia and hyperinsulinism, the latter in non-diabetic
      subjects.

PMID- 21940485
TI  - High-dose steroid treatment increases free water transport in peritoneal dialysis
      patients.
AB  - The water channel aquaporin-1 (AQP1) is the molecular counterpart of the
      ultrasmall pore that mediates free water transport during peritoneal dialysis
      (PD). Proof-of-principle studies performed in rats have shown that treatment with
      corticosteroids upregulates the expression of AQP1 in the peritoneal capillaries,
      causing a significant increase in free water transport. Whether such a beneficial
      effect could be observed in end-stage renal disease patients treated by PD
      remains unknown. Peritoneal transport parameters were evaluated in three patients
      on PD, shortly before and after living-donor renal transplantation and treatment
      with high-dose methylprednisolone (1.0-1.2 g/m(2)). As compared with pre
      transplantation values, the post-transplantation test revealed an ~2-fold
      increase in the sodium sieving and ultrasmall pore ultrafiltration volume,
      suggesting an effect on AQP1 water channels. In contrast, there was no change in
      the parameters of small solute transport. The direct involvement of AQP1 in these
      changes is suggested by the expression of glucocorticoid receptors in the human
      peritoneum and the presence of conserved glucocorticoid response elements in the
      promoter of the human AQP1 gene.

PMID- 21940486
TI  - Physical examination of dysfunctional arteriovenous fistulae by non
      interventionalists: a skill worth teaching.
AB  - BACKGROUND: Physical examination (PE) of arteriovenous fistulae (AVF) has
      recently emerged as an important element in the detection of stenotic lesions.
      This study examines the accuracy of PE in the assessment of AVF dysfunction by
      non-interventionalists in comparison with angiography. METHODS: A total of 177
      consecutive patients who had AVF dysfunction and were referred to our centre by
      general nephrologists for angioplasty between November 2009 and July 2010 were
      included in this analysis. Eleven referring general nephrologists completed a
      form reporting the PE findings regarding their patients' AVFs. Before angiography
      examination was carried out, a trained nephrology resident performed a PE in all
      the cases. Angiography of the AVFs was then performed by an interventionalist.
      Cohen's kappa value was used as the measurement of the level of agreement beyond
      chance between the diagnosis made on PE and angiography. RESULTS: There was a
      moderate agreement beyond chance between the general nephrologists' PE and
      angiography in the detection of AVF inflow stenosis (kappa = 0.49), outflow
      stenosis (kappa = 0.58) and thrombosis (kappa = 0.52). On the other hand, PE
      performed by the trained nephrology resident strongly agreed with angiography in
      the detection of AVF inflow stenosis (kappa = 0.84), outflow stenosis (kappa =
      0.92) and thrombosis (kappa = 0.98). The agreement between PE and angiography in
      the detection of co-existing AVF inflow-outflow stenosis was poor for the general
      nephrologists and moderate for the trained nephrology resident (kappa = 0.14
      versus kappa = 0.55, respectively). CONCLUSION: PE may provide an accurate means
      of diagnosis of AVF dysfunction. Theoretical and hands-on training in PE of
      dysfunctional AVFs should be provided for nephrologists in-training and for the
      dialysis staff.

PMID- 21940487
TI  - Discordant clinicopathological features in monozygotic twins with IgA
      nephropathy.
AB  - This report describes a pair of identical twins with IgA nephropathy (IgAN). One
      of them showed diffuse mesangial proliferation with crescent formations in the
      glomeruli, moderate proteinuria and required intensive therapies including
      corticosteroids for remission. In contrast, the other had only focal mesangial
      alterations and exhibited only a subtle level of urinary abnormalities throughout
      the follow-up without steroid therapy. Although our monozygotic twins have
      completely identical genotypes, the clinicopathological features of their IgAN
      were quite discordant. The present cases suggest that not only genetic factors
      but also epigenetic differences may be involved in the progression of IgAN.

PMID- 21940488
TI  - Serum uric acid and chronic kidney disease: the Severance cohort study.
AB  - BACKGROUND: Both serum uric acid (SUA) and chronic kidney disease (CKD) are
      associated with the risk of cardiovascular disease; however, it is unclear
      whether SUA independently increases the risk of CKD based on longitudinal data.
      METHODS: To investigate the relationship between SUA levels and CKD development,
      we initiated a 10.2-year prospective cohort study. Data from 14 939 Koreans, 20
      84 years of age, who completed a questionnaire and medical examination at the
      Severance Health Promotion Center were evaluated. The outcome of interest, CKD,
      was defined as an estimated glomerular filtration rate (GFR) of <60
      mL/min/1.73m(2) via the simplified Modification of Diet in Renal Disease
      equation. RESULTS: A multivariate Cox proportional hazard model, controlling for
      age, life style and other cardiovascular risk factors, showed an increased risk
      of developing CKD for men [hazard ratio (HR) 2.1; 95% confidence interval (CI)
      1.6-2.9] and women (HR = 1.3; 95% CI = 1.0-1.8) in the highest quartiles of SUA
      compared to their counterparts in the lowest quartiles. The relationship between
      SUA and CKD was linear and stepwise in men. The HRs for renal function Grade 2
      (75-89.9 mL/min/1.73m(2)), Grade 3 (60-74.9 mL/min/1.73m(2)) and Grade 4 (<60
      mL/min/1.73m(2)) increased with an increase in SUA quartiles as compared to the
      baseline GFR group (Grade 1, >=90 mL/min/1.73m(2)). CONCLUSIONS: Higher SUA
      levels increased the risk of CKD, suggesting that at least part of the reported
      association between SUA and cardiovascular disease may be connected to CKD.

PMID- 21940489
TI  - Effects of chronotherapy on blood pressure control in non-dipper patients with
      refractory hypertension.
AB  - BACKGROUND: Refractory arterial hypertension (RAH) is frequently associated to a
      non-dipping blood pressure (BP) pattern; this profile has been shown to have a
      worse clinical prognosis. It is a common clinical practice that patients receive
      anti-hypertensive medication preferentially in the morning. Non-dipping could be
      related to the timing of anti-hypertensive drug administration. We analysed
      whether switching anti-hypertensive medication to bedtime could improve BP
      control in non-dipper patients with RAH. METHODS: Twenty-seven consecutive
      patients with RAH and non-dipper or riser BP pattern on ambulatory blood pressure
      (ABP) monitoring were studied before and after 6 weeks of a change in the timing
      of anti-hypertensive medications. The intervention consisted of shifting all non
      diuretic anti-hypertensive drugs from morning to evening, maintaining the same
      drugs at the same doses. A parallel group of 12 consecutive patients with similar
      characteristics and no changes in the therapeutic regimen formed the control
      group. RESULTS: There were 59% women, mean age 65.7 +/- 8.4 years. They were
      treated with 4 +/- 0.7 anti-hypertensive drugs, 90% administered in the morning.
      At baseline, diurnal and nocturnal ABP averaged 141.6 +/- 10.6/81.5 +/- 9.3 and
      141.7 +/- 11/78 +/- 8.8, respectively. After the drug shift, mean diurnal and
      nocturnal ABP was 140.5 +/- 10.4/80.5 +/- 9.6 and 135.7 +/- 12.5/73.8 +/- 9.3 (P
      = 0.005 and 0.04 for systolic and diastolic ABP), 15% of the patients restored a
      normal ABP circadian rhythm. No changes were observed in the control group.
      CONCLUSION: In non-dipper or riser patients with RAH, changing the timing of anti
      hypertensive medication to the evening could improve BP control.

PMID- 21940490
TI  - Effect of cortical spreading depression on basal and evoked traffic in the
      trigeminovascular sensory system.
AB  - AIM: To use an animal model to test whether migraine pain arises peripherally or
      centrally. METHODS: We monitored the spontaneous and evoked activity of second
      order trigeminovascular neurons in rats to test whether traffic increased
      following a potential migraine trigger (cortical spreading depression, CSD) and
      by what mechanism any such change was mediated. RESULTS: Neurons (n = 33)
      responded to stimulation of the dura mater and facial skin with A-delta
      latencies. They were spontaneously active with a discharge rate of 6.1 +/- 6.4
      discharges s(-1). Injection of 10 ug lignocaine into the trigeminal ganglion
      produced a fully reversible reduction of the spontaneous discharge rate of
      neurons. Neuronal discharge rate returned to normal by 90 min. Lignocaine reduced
      the evoked responses of neurons to dural stimulation to 37% and to facial skin
      stimulation to 53% of control. Induction of CSD by cortical injection of KCl
      increased the spontaneous discharge rate of neurons from 2.9 to 16.3 discharges
      s(-1) at 20 min post CSD. Injection of 10 ug lignocaine into the trigeminal
      ganglion at this time failed to arrest or reverse this increase. Injection of
      lignocaine prior to the initiation of CSD failed to prevent the subsequent
      development of CSD-induced increases in discharge rates. CONCLUSIONS: These
      results suggest that there is a continuous baseline traffic in primary
      trigeminovascular fibres and that CSD does not act to increase this traffic by a
      peripheral action alone - rather, it must produce some of its effect by a
      mechanism intrinsic to the central nervous system. Thus the pain of migraine may
      not always be the result of peripheral sensory stimulation, but may also arise by
      a central mechanism.

PMID- 21940491
TI  - Gene expression networks in COPD: microRNA and mRNA regulation.
AB  - BACKGROUND: The mechanisms underlying chronic obstructive pulmonary disease
      (COPD) remain unclear. MicroRNAs (miRNAs or miRs) are small non-coding RNA
      molecules that modulate the levels of specific genes and proteins. Identifying
      expression patterns of miRNAs in COPD may enhance our understanding of the
      mechanisms of disease. A study was undertaken to determine if miRNAs are
      differentially expressed in the lungs of smokers with and without COPD. miRNA and
      mRNA expression were compared to enrich for biological networks relevant to the
      pathogenesis of COPD. METHODS: Lung tissue from smokers with no evidence of
      obstructive lung disease (n=9) and smokers with COPD (n=26) was examined for
      miRNA and mRNA expression followed by validation. We then examined both miRNA and
      mRNA expression to enrich for relevant biological pathways. RESULTS: 70 miRNAs
      and 2667 mRNAs were differentially expressed between lung tissue from subjects
      with COPD and smokers without COPD. miRNA and mRNA expression profiles enriched
      for biological pathways that may be relevant to the pathogenesis of COPD
      including the transforming growth factor beta, Wnt and focal adhesion pathways.
      miR-223 and miR-1274a were the most affected miRNAs in subjects with COPD
      compared with smokers without obstruction. miR-15b was increased in COPD samples
      compared with smokers without obstruction and localised to both areas of
      emphysema and fibrosis. miR-15b was differentially expressed within GOLD classes
      of COPD. Expression of SMAD7, which was validated as a target for miR-15b, was
      decreased in bronchial epithelial cells in COPD. CONCLUSIONS: miRNA and mRNA are
      differentially expressed in individuals with COPD compared with smokers without
      obstruction. Investigating these relationships may further our understanding of
      the mechanisms of disease.

PMID- 21940492
TI  - Monitoring treatment response in precapillary pulmonary hypertension using non
      invasive haemodynamic measurements.

PMID- 21940494
TI  - Attitudes regarding ski helmet use among helmet wearers and non-wearers.
AB  - OBJECTIVE: The aim of this study was to compare attitudes regarding ski helmet
      use in helmet wearers and non-wearers. METHODS: In total, 924 persons >=18 years
      (52% men and 48% women) participating in sport programmes at the University
      Sports Institute Innsbruck/Austria were interviewed about their attitudes
      regarding ski helmets and scored 14 statements on a five-level Likert Scale. A
      factor analysis was employed to determine clusters of underlying attitudes that
      have subsequently been used as predictors of helmet non-use in a conditional
      logistic regression analysis. RESULTS: In total, 65% of participants declared to
      use a helmet during their preferred winter sport activity while more than 80% of
      helmet wearers and non-wearers totally agreed that helmets protect from head
      injuries. According to the factor analysis, attitudes about ski helmets clustered
      around four major dimensions-subjective disadvantages, safety awareness,
      comfort/style and risk compensation. Adjusted ORs of regression analysis showed
      that helmet non-use increased with age and decreased with increasing skill level
      (beginner: OR 5.4, 95% CI 2.6 to 11.1; intermediate: OR 4.3, 95% CI 2.4 to 7.9;
      advanced: OR 3.1, 95% CI 1.7 to 5.4). In addition, helmet non-use was associated
      with subjective disadvantages (OR 2.3, 95% CI 1.8 to 2.9). However, a negative
      association between helmet non-use and safety awareness (OR 0.3, 95% CI 0.2 to
      0.4) was found. CONCLUSION: Helmet use was associated with higher safety
      awareness, while most arguments against helmet use seem to belong to subjective
      perception and to represent anticipatory negative cognitions, poorly supported by
      evidence. Therefore, evidence-based information about wearing a ski helmet should
      be implemented in preventive helmet campaigns focusing on non-wearers. In
      addition, health communication programmes should be instituted to get non
      helmeted skiers and snowboarders to try out helmets to eliminate their potential
      prejudices.

PMID- 21940496
TI  - Second- or third-party punishment? When self-interest hides behind apparent
      functional interventions.

PMID- 21940497
TI  - Disruption of insect diapause using agonists and an antagonist of diapause
      hormone.
AB  - The dormant state known as diapause is widely exploited by insects to circumvent
      winter and other adverse seasons. For an insect to survive, feed, and reproduce
      at the appropriate time of year requires fine coordination of the timing of entry
      into and exit from diapause. One of the hormones that regulates diapause in moths
      is the 24-aa neuropeptide, diapause hormone (DH). Among members of the
      Helicoverpa/Heliothis complex of agricultural pests, DH prompts the termination
      of pupal diapause. Based on the structure of DH, we designed several agonists
      that are much more active than DH in breaking diapause. One such agonist that we
      describe also prevents the entry into pupal diapause when administered to larvae
      that are environmentally programmed for diapause. In addition, we used the unique
      antagonist development strategy of incorporating a dihydroimidazole ("Jones")
      trans-Proline mimetic motif into one of our DH agonists, thereby converting the
      agonist into a DH antagonist that blocks the termination of diapause. These
      results suggest potential for using such agents or next-generation derivatives
      for derailing the success of overwintering in pest species.

PMID- 21940498
TI  - Similarities between long interspersed element-1 (LINE-1) reverse transcriptase
      and telomerase.
AB  - Long interspersed element-1 (LINE-1 or L1) retrotransposons encode two proteins
      (ORF1p and ORF2p) that contain activities required for conventional
      retrotransposition by a mechanism termed target-site primed reverse
      transcription. Previous experiments in XRCC4 or DNA protein kinase catalytic
      subunit-deficient CHO cell lines, which are defective for the nonhomologous end
      joining DNA repair pathway, revealed an alternative endonuclease-independent
      (ENi) pathway for L1 retrotransposition. Interestingly, some ENi
      retrotransposition events in DNA protein kinase catalytic subunit-deficient cells
      are targeted to dysfunctional telomeres. Here we used an in vitro assay to detect
      L1 reverse transcriptase activity to demonstrate that wild-type or endonuclease
      defective L1 ribonucleoprotein particles can use oligonucleotide adapters that
      mimic telomeric ends as primers to initiate the reverse transcription of L1 mRNA.
      Importantly, these ribonucleoprotein particles also contain a nuclease activity
      that can process the oligonucleotide adapters before the initiation of reverse
      transcription. Finally, we demonstrate that ORF1p is not strictly required for
      ENi retrotransposition at dysfunctional telomeres. Thus, these data further
      highlight similarities between the mechanism of ENi L1 retrotransposition and
      telomerase.

PMID- 21940499
TI  - Conformation of self-assembled porphyrin dimers in liposome vesicles by phase
      modulation 2D fluorescence spectroscopy.
AB  - By applying a phase-modulation fluorescence approach to 2D electronic
      spectroscopy, we studied the conformation-dependent exciton coupling of a
      porphyrin dimer embedded in a phospholipid bilayer membrane. Our measurements
      specify the relative angle and separation between interacting electronic
      transition dipole moments and thus provide a detailed characterization of dimer
      conformation. Phase-modulation 2D fluorescence spectroscopy (PM-2D FS) produces
      2D spectra with distinct optical features, similar to those obtained using 2D
      photon-echo spectroscopy. Specifically, we studied magnesium meso
      tetraphenylporphyrin dimers, which form in the amphiphilic regions of 1,2
      distearoyl-sn-glycero-3-phosphocholine liposomes. Comparison between experimental
      and simulated spectra show that although a wide range of dimer conformations can
      be inferred by either the linear absorption spectrum or the 2D spectrum alone,
      consideration of both types of spectra constrain the possible structures to a "T
      shaped" geometry. These experiments establish the PM-2D FS method as an effective
      approach to elucidate chromophore dimer conformation.

PMID- 21940500
TI  - Receptor for hyaluronan-mediated motility isoform B promotes liver metastasis in
      a mouse model of multistep tumorigenesis and a tail vein assay for metastasis.
AB  - The gene encoding the receptor for hyaluronan-mediated motility (RHAMM) is
      overexpressed in many human cancers. However, it is unclear whether RHAMM plays a
      causal role in tumor initiation or progression. Using somatic gene transfer in a
      mouse model of islet cell tumorigenesis, we demonstrate that RHAMM isoform B
      (RHAMM(B)) promotes tumor growth and metastases to lymph nodes and the liver. The
      propensity of RHAMM(B)-expressing cells to metastasize to the liver was confirmed
      using an experimental metastasis assay in which cells were injected into the tail
      vein of immunodeficient mice. However, RHAMM(B) did not increase cell migration
      or proliferation in culture. In initial efforts to identify signaling pathways
      activated by RHAMM(B), we found that RHAMM(B) induced phosphorylation of
      epidermal growth factor receptor (EGFR), Erk1/2, and STAT3 and conferred
      susceptibility to apoptosis after treatment with an EGFR inhibitor, gefitinib.
      Taken together, the results indicate that RHAMM(B) promotes hepatic metastasis by
      islet tumor cells, perhaps through growth factor receptor-mediated signaling.

PMID- 21940501
TI  - Defining the cellular precursors to human breast cancer.
AB  - Human breast cancers are broadly classified based on their gene-expression
      profiles into luminal- and basal-type tumors. These two major tumor subtypes
      express markers corresponding to the major differentiation states of epithelial
      cells in the breast: luminal (EpCAM(+)) and basal/myoepithelial (CD10(+)).
      However, there are also rare types of breast cancers, such as metaplastic
      carcinomas, where tumor cells exhibit features of alternate cell types that no
      longer resemble breast epithelium. Until now, it has been difficult to identify
      the cell type(s) in the human breast that gives rise to these various forms of
      breast cancer. Here we report that transformation of EpCAM(+) epithelial cells
      results in the formation of common forms of human breast cancer, including
      estrogen receptor-positive and estrogen receptor-negative tumors with luminal and
      basal-like characteristics, respectively, whereas transformation of CD10(+) cells
      results in the development of rare metaplastic tumors reminiscent of the claudin
      low subtype. We also demonstrate the existence of CD10(+) breast cells with
      metaplastic traits that can give rise to skin and epidermal tissues. Furthermore,
      we show that the development of metaplastic breast cancer is attributable, in
      part, to the transformation of these metaplastic breast epithelial cells. These
      findings identify normal cellular precursors to human breast cancers and reveal
      the existence of a population of cells with epidermal progenitor activity within
      adult human breast tissues.

PMID- 21940502
TI  - Diverse factors are involved in maintaining X chromosome inactivation.
AB  - X chromosome inactivation (XCI) is the most dramatic example of epigenetic
      silencing in eukaryotes. Once established, the inactivated X chromosome (Xi)
      remains silenced throughout subsequent cell divisions. Though the initiation of
      XCI has been studied extensively, the protein factors involved in Xi silencing
      and maintenance are largely unknown. Here we report the discovery of a diverse
      set of 32 proteins involved in maintenance of Xi silencing through a genome-wide
      RNAi screen. In addition, we describe the mechanistic roles of two proteins-
      origin recognition complex 2 (Orc2) and heterochromatin protein 1 (HP1alpha)--in
      Xi silencing. Immunofluorescence studies indicate that Orc2 and HP1alpha localize
      on Xi in mouse cells. Depletion of Orc2 by shRNA leads to the loss of both Orc2
      and HP1alpha localization on Xi. Furthermore, the silencing of genes on Xi is
      disrupted in both Orc2- and HP1alpha-depleted cells. Finally, we show, using ChIP
      assay, that the localization of HP1alpha and Orc2 to the promoter regions of Xi
      silenced genes is interdependent. These findings reveal a diverse set of proteins
      involved in Xi silencing, show how Orc2 and HP1alpha impact Xi silencing, and
      provide a basis for future studies on the maintenance of Xi silencing.

PMID- 21940503
TI  - A nucleolar protein, H19 opposite tumor suppressor (HOTS), is a tumor growth
      inhibitor encoded by a human imprinted H19 antisense transcript.
AB  - The H19 gene, which localizes within a chromosomal region on human chromosome
      11p15 that is commonly lost in Wilms tumor (WT), encodes an imprinted
      untranslated RNA. However, the biological significance of the H19 noncoding
      transcript remains unresolved because replacement of the RNA transcript with a
      neocassette has no obvious phenotypic effect. Here we show that the human H19
      locus also encodes a maternally expressed, translated gene, antisense to the
      known H19 transcript, which is conserved in primates. This gene, termed HOTS for
      H19 opposite tumor suppressor, encodes a protein that localizes to the nucleus
      and nucleolus and that interacts with the human enhancer of rudimentary homolog
      (ERH) protein. WTs that show loss of heterozygosity of 11p15 or loss of
      imprinting of IGF2 also silence HOTS (7/7 and 10/10, respectively).
      Overexpression of HOTS inhibits Wilms, rhabdoid, rhabdomyosarcoma, and
      choriocarcinoma tumor cell growth, and silencing HOTS by RNAi increases in vitro
      colony formation and in vivo tumor growth. These results demonstrate that the
      human H19 locus harbors an imprinted gene encoding a tumor suppressor protein
      within the long-sought WT2 locus.

PMID- 21940504
TI  - Improved perfusion MR imaging assessment of intracerebral tumor blood volume and
      antiangiogenic therapy efficacy in a rat model with ferumoxytol.
AB  - PURPOSE: To evaluate the consistency of tumor blood volume measurements and
      antiangiogenic therapy efficacy assessments with a low-molecular-weight
      gadolinium-based contrast agent (GBCA, gadodiamide) versus an iron oxide
      nanoparticle (ferumoxytol) in the presence or absence of a loading dose of
      contrast agent before perfusion magnetic resonance (MR) imaging (preload method).
      MATERIALS AND METHODS: The protocol was approved by the institutional animal care
      and use committee. U87MG tumor cells were implanted intracerebrally in 13 rats.
      All 13 rats underwent 11.75-T MR imaging with gadodiamide (60 MUL) 13 days after
      tumor implantation. The next day, nine rats underwent MR imaging with ferumoxytol
      (60 MUL). Immediately after ferumoxytol imaging, six rats received bevacizumab
      (45 mg/kg). MR imaging was repeated 48 hours after bevacizumab treatment with
      gadodiamide and 72 hours after treatment with ferumoxytol. Each study included
      three consecutive dynamic susceptibility-weighted contrast material-enhanced
      (DSC) MR acquisitions, which were performed without preload, with single-dose
      preload, and with double-dose preload. Tumor relative cerebral blood volume
      (rCBV) was estimated from each DSC MR acquisition. Two-way repeated measures
      analysis of variance was performed to test for differences between groups with
      both contrast agents. RESULTS: DSC MR imaging with gadodiamide and without
      preload showed low rCBV (<= 1.75) in nine of the 13 tumors; estimated rCBV
      increased progressively with both single- and double-dose preloads (P < .001).
      Conversely, rCBVs obtained with ferumoxytol were high (>1.75) and remained
      constant with all three acquisitions. The magnitude of rCBV decrease after
      bevacizumab administration was dependent on the dose of gadodiamide preload,
      whereas the magnitude of rCBV decrease with ferumoxytol was constant regardless
      of whether contrast agent preload was used. CONCLUSION: With GBCA, tumor rCBV can
      be underestimated without preload and becomes dose dependent with preload
      correction. Conversely, ferumoxytol provides consistent assessment of tumor rCBV
      and antiangiogenic therapy efficacy.

PMID- 21940505
TI  - Contrast-enhanced CT of articular cartilage: experimental study for
      quantification of glycosaminoglycan content in articular cartilage.
AB  - PURPOSE: To investigate the diagnostic potential of delayed contrast material
      enhanced computed tomography (CT) of articular cartilage in quantification of
      glycosaminoglycan (GAG) concentration in normal and degenerated articular
      cartilage ex vivo by using a clinical CT scanner. MATERIALS AND METHODS: This
      study was exempted by the institutional and animal review boards, and informed
      consent was not required. Forty intact porcine patellae were extracted and
      assigned to either a control (n = 20) or a trypsin-treated group (ie, GAG
      depleted group) (n = 20). Ten patellae in each group were immersed in anionic
      contrast agent (ioxaglate, 40%) and the other ten in neutral contrast agent
      (iopromide, 35%) for 2 hours. To determine the contrast agent concentration
      within cartilage, samples were scanned with a clinical CT scanner immediately
      after the immersion time, and the x-ray attenuation of cartilage was measured. CT
      images were compared with safranin O-stained histologic sections, and actual GAG
      contents were determined with a dimethylmethylene blue assay. RESULTS: Ioxaglate
      was taken up by GAG-depleted cartilage to a greater extent than by normal
      cartilage (P = .01). In contrast, the penetration of iopromide was not
      significantly different between GAG-depleted and normal cartilage (P = .1). The
      loss of GAGs in trypsin-treated cartilage was confirmed microscopically by using
      safranin O-stained sections, and a dimethylmethylene blue assay also confirmed
      that GAG content was markedly decreased in trypsin-treated cartilage (P = .003).
      CONCLUSION: This study showed that contrast-enhanced CT images of articular
      cartilage could reflect the GAG content within the cartilage by allowing
      measurement of the concentration of anionic iodine-based contrast agent
      accumulated in the cartilage.

PMID- 21940506
TI  - Integration of 64-detector lower extremity CT angiography into whole-body trauma
      imaging: feasibility and early experience.
AB  - PURPOSE: To evaluate the image quality and clinical utility of a polytrauma
      computed tomographic (CT) protocol that integrates lower extremity CT angiography
      into multiphasic whole-body trauma CT by utilizing 64-detector CT and a single
      contrast material bolus. MATERIALS AND METHODS: This retrospective study was
      institutional review board approved and HIPAA compliant. Informed consent was
      waived. All patients who underwent CT angiography of the lower extremities
      integrated with multiphasic torso CT for trauma between May 2005 and September
      2009 were included. Two hundred eighty-four patients met the inclusion criteria.
      The mechanism of trauma was blunt injury in 228 (80.3%) of 284 patients and
      penetrating in 56 (19.7%) of 284 patients. CT angiography encompassed the joints
      proximal and distal to the injured region, with scan delay fixed at 25 seconds.
      Two radiologists retrospectively reviewed all the extremity CT angiograms, noting
      the presence of vascular injury, and measured the attenuation in the lower
      extremity arteries. Arterial attenuation, in Hounsfield units, was measured at
      multiple vascular divisions, and CT angiographic results were compared with
      clinical outcome, and if available, repeat lower extremity CT angiographic,
      conventional angiographic, or surgical findings. Sensitivity and specificity with
      95% confidence intervals were calculated. RESULTS: Sixty-three arterial injuries
      were identified in 44 (15.5%) of 284 patients as follows: occlusion (n = 37),
      narrowing (n = 9), active extravasation (n = 14), pseudoaneurysm (n= 2), and
      arteriovenous fistula (n = 1). Three patients underwent conventional angiography
      after CT angiography. Seven patients underwent surgical therapy with all CT
      angiographic findings confirmed. There were no injuries subsequently identified
      in the subgroup with a negative result at CT angiography. Of the 864 vascular
      divisions in which attenuation was measured, 69 (8%) of 864 had a mean
      attenuation less than 150 HU. CONCLUSION: Integration of lower extremity CT
      angiography into multiphasic whole-body trauma imaging is feasible, helps detect
      clinically relevant vascular injuries, and results in diagnostic image quality in
      the majority of patients.

PMID- 21940507
TI  - Echocardiographic variables after left ventricular assist device implantation
      associated with adverse outcome.
AB  - BACKGROUND: Operative mortality after left ventricular assist device (LVAD)
      implantation is heavily influenced by patient selection and the technical
      difficulty of surgery. However, how we treat our patients and LVAD setting may
      affect the patient outcome beyond this period. We postulated that the presence of
      echocardiographic variables 1 month after surgery suggesting appropriate degree
      of LV unloading and an adequate forward flow would be important in determining
      clinical outcomes after the initial successful LVAD implantation. METHODS AND
      RESULTS: We retrospectively analyzed various variables in echocardiographic
      examinations performed 30 days after LVAD implant in 76 consecutive patients
      receiving continuous flow device for their association with a compound end point
      (90-day mortality, readmission for heart failure, or New York Heart Association
      class III or higher at the end of the 90-day period). The echocardiographic
      associations examined included estimated LVAD flow, with and without native LV
      contribution, interventricular septal position, the status of aortic valve
      opening, an estimated left atrial pressure (ELAP), the mitral flow E-wave
      deceleration time, and the ratio of deceleration time to E-wave velocity (mitral
      deceleration index [MDI]). Four patients died during the 30- to 90-day period, 6
      patients were readmitted for heart failure, and 25 patients were considered to
      have New York Heart Association class III or higher at the end of the 90-day
      period. Variables associated with adverse outcome included increased ELAP (odds
      ratio, 1.30 [1.16-1.48]; P<0.0001), MDI <2 ms/[cm/s] (odds ratio, 4.4
      implantation [1.22-18]; P=0.02) and decreased tricuspid lateral annulus velocity
      (odds ratio, 0.70 implantation [0.48-0.95]; P=0.02). A leftward deviation of
      interventricular septum was associated with a worse outcome (odds ratio, 3.03
      implantation [1.21-13.3]; P=0.01). CONCLUSIONS: Mortality and heart failure after
      LVAD surgery appear to be predominantly determined by echocardiographic evidence
      of inefficient unloading of the left ventricle and persistence of right
      ventricular dysfunction. Increased estimated LA pressure and short MDI are
      associated with worse mid term outcome. Leftward deviation of the septum is
      associated with worse outcome as well.

PMID- 21940508
TI  - Consumption of a resistant protein, sericin, elevates fecal immunoglobulin A,
      mucins, and cecal organic acids in rats fed a high-fat diet.
AB  - We previously reported that consumption of a resistant protein, sericin, reduces
      colon tumorigenesis, constipation, and serum TG in rodents. The present study was
      conducted to elucidate the effects of dietary sericin on the intestinal luminal
      environment in rats fed a high-fat (HF) diet. Rats were fed 300 or 50 g/kg of
      beef tallow with or without 40 g/kg sericin, a protein purified from cocoons of
      Bombix mori, for 3 wk. Intestinal luminal variables, including IgA (index of
      intestinal immune function), mucins (index of barrier function), organic acids,
      microflora, and secondary bile acids, were measured. Dietary sericin markedly
      elevated fecal IgA in the HF diet group (3-fold, P < 0.05) but not in the low-fat
      (LF) diet group. Fecal mucin levels were elevated by sericin intake in the HF
      diet group (P < 0.05). Cecal organic acids, including acetate, propionate, n
      butyrate, and succinate, were significantly lower in the HF diet group compared
      with the LF diet group. Dietary sericin significantly elevated cecal acetate and
      n-butyrate in the HF diet group but not in the LF diet group. Compared with the
      LF diet, the HF diet significantly increased serum TG in the untreated group but
      not in those fed sericin. The HF diet increased lower density lipoprotein (VLDL +
      IDL + LDL) cholesterol and it was reduced by sericin intake (P < 0.05). There was
      an inverse correlation between serum TG and cecal acetate (Spearman rank
      correlation coefficient = -0.63; P < 0.001). The profile of microflora in cecal
      digesta and fecal secondary bile acids (a risk factor for colon cancer) did not
      differ between the HF diet and HF diet with sericin groups. These results suggest
      a novel and favorable effect of sericin on colon health by modulating intestinal
      immune and barrier functions and fermentation in rats fed a HF diet.

PMID- 21940509
TI  - Early life exposure to isoflavones adversely affects reproductive health in first
      but not second generation female CD-1 mice.
AB  - Soy-based infant formula (SBIF) can be a substantial source of soy isoflavones
      during early life. Because soy isoflavones have the capacity to mimic endogenous
      estrogen and thereby exert hormone-like effects, there is concern regarding
      reproductive health. The objectives were to determine if neonatal exposure to soy
      isoflavones altered reproductive health in females and, if so, whether such
      effects are transferred to subsequent generations. CD-1 mice were bred and F1
      mouse offspring were cross-fostered at birth and randomized to 1 of 4 treatments:
      7 mg soy isoflavones . kg body weight(-1) . d(-1) or corn oil from postnatal d
      (PND) 1 to 10 or from PND 1 to 21 (n = 8-13 females/group). Mice were
      subsequently bred to control males on PND 56 to obtain F2 females (n = 10
      15/group). F1 mice that received isoflavones had ~15% greater body weight during
      wk 4-8 and markedly reduced fertility with a 55-60% success rate. Reduced
      fertility was associated with abnormal estrus cycles, fewer corpora lutea in
      ovaries, and increased incidence of hyperplasia and atypia in the uteri.
      Offspring (F2 mice) of isoflavone-treated F1 mice had ~15% higher body weight by
      wk 8 through 16 of age than controls and fertility was normal. In summary, early
      exposure to soy isoflavones resulting in serum isoflavone concentrations similar
      to human infants fed SBIF reduced fertility in F1 but not F2 mice and increased
      body weight in both generations of female offspring. Extrapolation of these
      findings to the human scenario are complex but can provide guidance for more
      fully understanding the implications for infants consuming SBIF.

PMID- 21940510
TI  - Postprandial hyperglycemia impairs vascular endothelial function in healthy men
      by inducing lipid peroxidation and increasing asymmetric
      dimethylarginine:arginine.
AB  - Postprandial hyperglycemia induces vascular endothelial dysfunction (VED) and
      increases future cardiovascular disease risk. We hypothesized that postprandial
      hyperglycemia would decrease vascular function in healthy men by inducing
      oxidative stress and proinflammatory responses and increasing asymmetric
      dimethylarginine:arginine (ADMA:arginine), a biomarker that is predictive of
      reduced NO biosynthesis. In a randomized, cross-over design, healthy men (n = 16;
      21.6 +/- 0.8 y) ingested glucose or fructose (75 g) after an overnight fast.
      Brachial artery flow-mediated dilation (FMD), plasma glucose and insulin,
      antioxidants, malondialdehyde (MDA), inflammatory proteins, arginine, and ADMA
      were measured at regular intervals during the 3-h postprandial period. Baseline
      FMD did not differ between trials (P > 0.05). Postprandial FMD was reduced
      following the ingestion of glucose only. Postprandial MDA concentrations
      increased to a greater extent following the ingestion of glucose compared to
      fructose. Plasma arginine decreased and the ratio of ADMA:arginine increased to a
      greater extent following the ingestion of glucose. Inflammatory cytokines and
      cellular adhesion molecules were unaffected by the ingestion of either sugar.
      Postprandial AUC(0-3 h) for FMD and MDA were inversely related (r = -0.80; P <
      0.05), suggesting that hyperglycemia-induced lipid peroxidation suppresses
      postprandial vascular function. Collectively, these findings suggest that
      postprandial hyperglycemia in healthy men reduces endothelium-dependent
      vasodilation by increasing lipid peroxidation independent of inflammation.
      Postprandial alterations in arginine and ADMA:arginine also suggest that acute
      hyperglycemia may induce VED by decreasing NO bioavailability through an
      oxidative stress-dependent mechanism. Additional work is warranted to define
      whether inhibiting lipid peroxidation and restoring arginine metabolism would
      mitigate hyperglycemia-mediated decreases in vascular function.

PMID- 21940511
TI  - Milk intakes are not associated with percent body fat in children from ages 10 to
      13 years.
AB  - Epidemiologic studies report conflicting results for the relationship between
      milk intake and adiposity in children. We examined prospective and cross
      sectional associations between milk intake and percent body fat among 2245
      children from the Avon Longitudinal Study of Parents and Children. Cross
      sectional analyses were performed at age 13 y between total, full-fat, and
      reduced-fat milk intake assessed using 3-d dietary records and body fat from DXA.
      Prospective analyses were conducted between milk intakes at age 10 y and body fat
      at 11 and 13 y. Models were adjusted for age, sex, height, physical activity,
      pubertal status, maternal BMI, maternal education, and intakes of total fat,
      sugar-sweetened beverages, 100% fruit juice, and ready-to-eat cereals; baseline
      BMI was added to prospective models. Subset analyses were performed for those
      with plausible dietary intakes. Mean milk consumption at 10 and 13 y was (mean +/
      SD) 0.90 +/- 0.73 and 0.85 +/- 0.78 servings/d [1 serving = 8 oz of milk (244 g
      of plain and 250 g flavored milk)], respectively. Cross-sectional results
      indicated an inverse association between full-fat milk intake and body fat [beta
      = -0.47 (95% CI = -0.76, -0.19); P = 0.001]. Milk intake at age 10 y was
      inversely associated with body fat at 11 y [beta = -0.16 g/d (95%CI = -0.28, 
      0.04); P = 0.01], but not among those with plausible dietary intakes, suggesting
      that this association was influenced by dietary measurement errors. Milk intake
      was not associated with body fat at age 13 y after adjustment. Although our
      prospective results corroborate other findings of a null associations between
      milk intake and adiposity, our inconsistent findings across analyses suggest
      further investigation is needed to clarify the relation, and accounting for
      dietary reporting errors is an important consideration.

PMID- 21940512
TI  - Dietary ellagic acid attenuates oxidized LDL uptake and stimulates cholesterol
      efflux in murine macrophages.
AB  - Foam cell formation is the hallmark of early atherosclerosis. Lipid uptake by
      scavenger receptors (SR) in macrophages initiates chronic proinflammatory
      cascades linked to atherosclerosis. It has been reported that the upregulation of
      cholesterol efflux may be protective in the development of atherosclerosis.
      Ellagic acid, a polyphenolic compound mostly found in berries, walnuts, and
      pomegranates, possesses antioxidative, growth-inhibiting and apoptosis-promoting
      activities in cancer cells. However, the antiatherogenic actions of ellagic acid
      are not well defined. The current study elucidated oxidized LDL handling of
      ellagic acid in J774A1 murine macrophages. Noncytotoxic ellagic acid suppressed
      SR-B1 induction and foam cell formation within 6 h after the stimulation of
      macrophages with oxidized LDL, confirmed by Oil red O staining of macrophages.
      Ellagic acid at <=5 MUmol/L upregulated PPARgamma and ATP binding cassette
      transporter-1 in lipid-laden macrophages, all responsible for cholesterol efflux.
      In addition, 5 MUmol/L ellagic acid accelerated expression and transcription of
      the nuclear receptor of liver X receptor-alpha highly implicated in the PPAR
      signaling. Furthermore, ellagic acid promoted cholesterol efflux in oxidized LDL
      induced foam cells. These results provide new information that ellagic acid
      downregulated macrophage lipid uptake to block foam cell formation of macrophages
      and boosted cholesterol efflux in lipid-laden foam cells. Therefore, dietary and
      pharmacological interventions with berries rich in ellagic acid may be promising
      treatment strategies to interrupt the development of atherosclerosis.

PMID- 21940513
TI  - Dietary phospholipids ameliorate fructose-induced hepatic lipid and metabolic
      abnormalities in rats.
AB  - Overconsumption of fructose results in hepatic dyslipidemia, which has a
      documented correlation with metabolic syndrome. We examined whether the ingestion
      of phospholipids (PL) from soybeans prevents fructose-induced metabolic
      abnormalities. Rats were fed either a fructose-free diet (C), a 60% fructose diet
      (F), or a 60% fructose plus 3% PL diet (F-PL) for 10 wk. At wk 8, plasma glucose
      concentrations after glucose loading were significantly higher in rats fed the F
      diet than in rats fed the C and F-PL diets, which did not differ from one
      another. The concentrations of hepatic TG, diglycerides, ceramides, and oleates
      in rats fed the F diet for 10 wk was significantly higher than those in rats fed
      the C diet. The increases were prevented by concurrent PL ingestion;
      concentrations did not differ between the F-PL and C groups. Dietary fructose
      increased the mRNA expression of SREBP1, ChREBP, and genes related to
      lipogenesis. PL completely inhibited these increases. Furthermore, reflecting the
      difference at the mRNA level, lipogenic enzyme activities were greater in rats
      fed the F diet than in rats fed the C diet, and PL ingestion suppressed the
      increased activities by fructose feeding. Treatment of cultured Hep-G2 cells with
      fructose for 24 h increased the levels of SREBP1 and ChREBP nuclear proteins,
      which were suppressed by culture with purified PL components, especially
      phosphatidylethanolamine and phosphatidylinositol. These findings indicate that
      PL prevents fructose-induced metabolic abnormalities in association with
      alterations of the hepatic lipid profile by inhibiting de novo lipogenesis.

PMID- 21940514
TI  - A diet high in low-fat dairy products lowers diabetes risk in postmenopausal
      women.
AB  - Some previous studies have suggested that consuming dairy products, particularly
      the low-fat variety, lowers the incidence of type 2 diabetes. However, no study
      to our knowledge has focused on an ethnically diverse group of postmenopausal
      women, a population with a high risk of this disease. We conducted a prospective
      cohort study of 82,076 postmenopausal women enrolled in the Women's Health
      Initiative Observational Study who did not report diabetes at enrollment. Total,
      low-fat, and high-fat dairy product and yogurt intakes were estimated from FFQ at
      baseline and 3 y of follow-up. Treated diabetes incidence was ascertained from
      annual follow-up questionnaires. During 8 y of follow-up, 3946 cases of incident
      treated diabetes were reported (annual incidence, 0.73%; cumulative incidence,
      4.8%). After multivariable adjustment, low-fat dairy product consumption was
      inversely associated with the risk of type 2 diabetes. RR was roughly 0.5-0.6 in
      the upper quintiles compared with the lowest quintile (median servings/d, 2.8 in
      the 5th quintile and 1.5 in the 4th quintile vs. 0.05 in the first quintile; P
      trend < 0.001). The inverse relationship was more pronounced in women with a
      higher BMI. High yogurt consumption was associated with a significant decrease in
      diabetes risk, whereas there was no relationship between high-fat dairy product
      consumption and diabetes risk. A diet high in low-fat dairy products is
      associated with lower diabetes risk in postmenopausal women, particularly those
      who are obese.

PMID- 21940515
TI  - The calcium-sensing receptor affects fat accumulation via effects on
      antilipolytic pathways in adipose tissue of rats fed low-calcium diets.
AB  - Low-calcium intake is associated with increased risk of obesity, but the
      mechanism underlying this is not clear. We previously reported that the calcium
      sensing receptor (CaSR) plays an important role in modulating the expression of
      rate-limiting lipolysis enzymes in human adipocytes. In the present study, rats
      were fed diets containing normal [0.50% (NC)], low [0.30% (LC)], or very low
      [0.15% (VLC)] calcium for 15 wk. Ten rats of each group were killed at wk 5, 10,
      and 15 of the intervention. The LC-fed rats had greater visceral fat mass, lower
      serum FFA and glycerol concentrations, and greater CaSR expression in white
      adipose tissue than did those fed the NC diet at wk 10 and 15. Hormone-sensitive
      lipase (HSL) and adipose TG lipase (ATGL) protein levels were lower, whereas
      fatty acid synthase mRNA in white adipose tissue was greater in the LC-fed rats
      compared with the NC-fed rats. These differences from the NC group were greater
      in the VLC group than in the LC group at wk 15. In vitro experiments showed that
      1,25-dihydroxycholecalciferol stimulated the expression of CaSR through the
      nuclear vitamin D receptor (nVDR). This resulted in an antilipolytic effect by
      increasing intracellular calcium, decreasing the intracellular cAMP level, and
      downregulating HSL and ATGL protein expression in adipocytes. These effects were
      suppressed by either nVDR or CaSR small-interfering RNA. These results suggest
      that CaSR affects fat accumulation by mediating antilipolytic pathways in adipose
      tissue of rats fed low-calcium diets.

PMID- 21940516
TI  - A Western-type diet attenuates pulmonary hypertension with heart failure and
      cardiac cachexia in rats.
AB  - Western-type diets (WD) constitute risk factors for disease but may have distinct
      effects in heart failure (HF) with cardiac cachexia (CC). We evaluated
      hemodynamic, metabolic, and inflammatory effects of short-term WD intake in
      pulmonary hypertension (PH) with CC. Male Wistar rats randomly received 60 mg .
      kg(-1) monocrotaline (M) or vehicle (C) and consumed either a 5.4-kcal . g(-1) WD
      (35% animal fat, 35% simple carbohydrate, 20% protein, 0.4% Na(+)) or a 2.9-kcal
      . g(-1) (3% vegetable fat, 60% complex carbohydrate, 16% protein, 0.25% Na(+))
      normal diet (ND) for 5 wk. Mortality, energy intake, body weight (BW),
      metabolism, hemodynamics, histology, apoptosis, gene expression, transcription
      factors, and plasma cytokines were evaluated. Compared with the C-ND group, the M
      ND group had PH, HF, and mortality that were significantly attenuated in M-WD.
      The extent of myocardial remodeling and apoptosis was higher in M-ND than in C-ND
      but lower in M-WD than in M-ND, while conversely, energy intake, BW, cholesterol,
      and TG plasma concentrations were lower in M-ND than in C-ND but higher in M-WD
      than in M-ND. M-ND had increased myocardial NF-kappaB transcription factor
      activity, endothelin-1, and cytokine overexpression and higher circulating
      cytokine concentrations than C-ND, which were lower in M-WD than in M-ND.
      PPARalpha activity, however, was lower in M-ND, but not in M-WD, compared with
      the respective C groups. WD attenuated PH and CC, ameliorating survival,
      myocardial function, metabolism, and inflammation, through transcription factor
      modulation, suggesting a beneficial role in CC.

PMID- 21940517
TI  - Regeneration of periodontal tissues in non-human primates with rhGDF-5 and beta
      tricalcium phosphate.
AB  - The application of growth factors has been advocated in support of periodontal
      regeneration. Recombinant human growth and differentiation factor-5 (rhGDF-5), a
      member of the bone morphogenetic protein family, has been used to encourage
      periodontal tissue regeneration. This study evaluated the dose response of rhGDF
      5 lyophilized onto beta-tricalcium phosphate (bTCP) granules for periodontal
      tissue regeneration in a baboon model. Periodontal defects were created
      bilaterally in 12 baboons by a split-mouth design. Plaque was allowed to
      accumulate around wire ligatures to create chronic disease. After 2 mos, the
      ligatures were removed, and a notch was placed at the base of the defect. Two
      teeth on each side of the mouth were randomly treated with bTCP only, 0.5, 1.0,
      or 2.0 mg rhGDF-5/g bTCP. Animals were sacrificed 5 mos post-treatment, with
      micro-CT and histomorphometric analysis performed. After 5 mos, analysis showed
      alveolar bone, cementum, and periodontal ligament formation in all treatment
      groups, with a dose-dependent increase in rhGDF-5-treated groups. Height of
      periodontal tissues also increased with the addition of rhGDF-5, and the amount
      of residual graft material decreased with rhGDF-5 treatment. Therefore, rhGDF-5
      delivered on bTCP demonstrated effective regeneration of all 3 tissues critical
      for periodontal repair.

PMID- 21940518
TI  - Meta-analysis of dysphagia and aspiration pneumonia in frail elders.
AB  - As part of a systematic literature review, a comprehensive literature search was
      carried out to identify risk factors for aspiration pneumonia in frail older
      people. A prominent risk factor found was dysphagia with evidence level 2a,
      according to the Oxford Centre for Evidence-based Medicine Levels of Evidence.
      Subsequently, a meta-analysis of 4 cohort, 1 case-cohort, and 1 case-control
      study on dysphagia as a risk factor of aspiration pneumonia in frail older people
      was performed. Using a random effects model, we found a positive correlation
      between dysphagia and aspiration pneumonia: OR = 9.84; 95%CI = 4.15 - 23.33 (test
      for statistical homogeneity: p < 0.001). Then, a subgroup meta-analysis was
      performed with 4 cohort studies, all including patients with a cerebrovascular
      disease. Once again, a positive correlation was found between dysphagia and
      aspiration pneumonia: OR = 12.93; 95%CI = 8.61 - 19.44. The test for statistical
      homogeneity revealed no statistically significant result (p = 0.15). It was
      concluded that dysphagia is a serious risk factor for aspiration pneumonia in
      frail older people, particularly in those suffering from a cerebrovascular
      disease.

PMID- 21940519
TI  - Metabolomic effects of xylitol and fluoride on plaque biofilm in vivo.
AB  - Dental caries is initiated by demineralization of the tooth surface through acid
      production from sugar by plaque biofilm. Fluoride and xylitol have been used
      worldwide as caries-preventive reagents, based on in vitro-proven inhibitory
      mechanisms on bacterial acid production. We attempted to confirm the inhibitory
      mechanisms of fluoride and xylitol in vivo by performing metabolome analysis on
      the central carbon metabolism in supragingival plaque using the combination of
      capillary electrophoresis and a time-of-flight mass spectrometer. Fluoride (225
      and 900 ppm F(-)) inhibited lactate production from 10% glucose by 34% and 46%,
      respectively, along with the increase in 3-phosphoglycerate and the decrease in
      phosphoenolpyruvate in the EMP pathway in supragingival plaque. These results
      confirmed that fluoride inhibited bacterial enolase in the EMP pathway and
      subsequently repressed acid production in vivo. In contrast, 10% xylitol had no
      effect on acid production and the metabolome profile in supragingival plaque,
      although xylitol 5-phosphate was produced. These results suggest that xylitol is
      not an inhibitor of plaque acid production but rather a non-fermentative sugar
      alcohol. Metabolome analyses of plaque biofilm can be applied for monitoring the
      efficacy of dietary components and medicines for plaque biofilm, leading to the
      development of effective plaque control.

PMID- 21940520
TI  - Periodontitis predicts elevated C-reactive protein levels in chronic kidney
      disease.
AB  - Based on the existing evidence supporting a state of chronic inflammation in
      chronic kidney disease (CKD), we hypothesized that periodontal infection may
      affect the systemic inflammatory status of a nationally representative CKD
      population as measured by serum C-reactive protein (CRP). We examined this
      hypothesis using the National Health and Nutrition Examination Survey 1988-1994
      (NHANES III) dataset including 2303 individuals. We followed the American Academy
      of Periodontology (AAP)/Centers for Disease Control and Prevention (CDC) case
      definition for periodontitis. We used a cutoff point of 30% sites with (PD) >= 5
      mm and (CAL) >= 4 mm to define generalized periodontitis cases. We estimated
      glomerular filtration rate based on cystatin C levels using the relevant
      equation. Urinary albumin-to-creatinine ratio was calculated in milligrams per
      gram with a cutoff point of 30 mg/g. CKD was defined based on eGFR < 60
      mL/min/1.73 m(2) and albuminuria >= 30 mg/g. Periodontitis was found in 427
      (12.3%) individuals. Of individuals with periodontitis, 41.8% had serum CRP
      higher than 0.3 mg/dL compared with 27.1% of non-periodontitis and 53.1% of
      edentulous individuals (p = 0.001 for all comparisons). When the extent of
      periodontitis was used as one of the independent variables, the parsimonious
      model showed a strong independent association between extent of periodontitis and
      serum CRP levels (OR = 2.0, CI95% = 1.2-3.6).

PMID- 21940521
TI  - Effect of UVA-activated riboflavin on dentin bonding.
AB  - Recent studies have reported collagen cross-linking after exposure to riboflavin
      followed by ultraviolet-A (UVA) exposure. This study is the first to investigate
      the effect of a riboflavin-containing primer on adhesive interface stability and
      dentinal matrix metalloproteinase activity. Human dentin was etched with 35%
      phosphoric acid, treated with 0.1% riboflavin, exposed to UVA for 2 min, and
      bonded with a two-step etch-and-rinse adhesive. Adhesive was applied to control
      specimens without riboflavin/UVA. Specimens were subjected to microtensile bond
      strength tests and pulled to failure after storage for 24 hrs, 6 mos, or 1 yr.
      Interfacial nanoleakage was evaluated by light and transmission electron
      microscopy. To investigate dentinal matrix metalloproteinase activity, we
      performed correlative zymographic assays on protein extracts obtained from
      phosphoric-acid-etched dentin powder with or without riboflavin/UVA treatment and
      XP Bond. Ultraviolet-activated riboflavin treatment increased the immediate bond
      strength to dentin at all aging intervals (p < 0.05 vs. control) and decreased
      interfacial nanoleakage in aged specimens (1 yr; p < 0.05). Zymograms revealed
      that riboflavin/UVA pre-treatment inhibited dentinal matrix metalloproteinase
      activity (especially MMP-9). In conclusion, dentinal collagen cross-linking
      induced by riboflavin/UVA increased immediate bond strength, stabilized the
      adhesive interface, and inhibited dentin matrix metalloproteinases, thereby
      increasing the durability of resin-dentin bonds.

PMID- 21940522
TI  - Genome-wide association scan for childhood caries implicates novel genes.
AB  - Dental caries is the most common chronic disease in children and a major public
      health concern due to its increasing incidence, serious health and social co
      morbidities, and socio-demographic disparities in disease burden. We performed
      the first genome-wide association scan for dental caries to identify associated
      genetic loci and nominate candidate genes affecting tooth decay in 1305 US
      children ages 3-12 yrs. Affection status was defined as 1 or more primary teeth
      with evidence of decay based on intra-oral examination. No associations met
      strict criteria for genome-wide significance (p < 10E-7); however, several loci
      (ACTN2, MTR, and EDARADD, MPPED2, and LPO) with plausible biological roles in
      dental caries exhibited suggestive evidence for association. Analyses stratified
      by home fluoride level yielded additional suggestive loci, including TFIP11 in
      the low-fluoride group, and EPHA7 and ZMPSTE24 in the sufficient-fluoride group.
      Suggestive loci were tested but not significantly replicated in an independent
      sample (N = 1695, ages 2-7 yrs) after adjustment for multiple comparisons. This
      study reinforces the complexity of dental caries, suggesting that numerous loci,
      mostly having small effects, are involved in cariogenesis.
      Verification/replication of suggestive loci may highlight biological mechanisms
      and/or pathways leading to a fuller understanding of the genetic risks for dental
      caries.

PMID- 21940523
TI  - Osteogenic potential of autogenous bone grafts harvested with four different
      surgical techniques.
AB  - The osteogenic potential of autogenous bone grafts is superior to that of
      allografts and xenografts because of their ability to release osteoinductive
      growth factors and provide a natural osteoconductive surface for cell attachment
      and growth. In this in vitro study, autogenous bone particles were harvested by
      four commonly used techniques and compared for their ability to promote an
      osteogenic response. Primary osteoblasts were isolated and seeded on autogenous
      bone grafts prepared from the mandibles of miniature pigs with a bone mill, piezo
      surgery, bone scraper, and bone drill (bone slurry). The osteoblast cultures were
      compared for their ability to promote cell attachment, proliferation, and
      differentiation. After 4 and 8 hrs, significantly higher cell numbers were
      associated with bone mill and bone scraper samples compared with those acquired
      by bone slurry and piezo-surgery. Similar patterns were consistently observed up
      to 5 days. Furthermore, osteoblasts seeded on bone mill and scraper samples
      expressed significantly elevated mRNA levels of collagen, osteocalcin, and
      osterix at 3 and 14 days and produced more mineralized tissue as assessed by
      alizarin red staining. These results suggest that the larger bone graft particles
      produced by bone mill and bone scraper techniques have a higher osteogenic
      potential than bone slurry and piezo-surgery.

PMID- 21940524
TI  - In a radiology department during the earthquake, tsunami, and nuclear power plant
      accident.

PMID- 21940525
TI  - Imaging of biliary tract disease.

PMID- 21940526
TI  - The practice of radiology: current and future trends.

PMID- 21940527
TI  - Liver, gastrointestinal, and cardiac toxicity in intermediate hepatocellular
      carcinoma treated with PRECISION TACE with drug-eluting beads: results from the
      PRECISION V randomized trial.
AB  - OBJECTIVE: The purpose of our study was to evaluate hepatic, gastrointestinal,
      and cardiac toxicity after PRECISION transarterial chemoembolization (TACE) with
      drug-eluting beads (DEB) versus conventional TACE with doxorubicin in the
      treatment of intermediate-stage hepatocellular carcinoma (HCC). SUBJECTS AND
      METHODS: Two hundred twelve patients (185 men and 27 women; mean age, 67 years)
      were randomized to TACE with DEB or conventional TACE. The majority of patients
      (67% in both groups) presented in a more advanced stage. Safety was measured by
      rate of adverse events (Southwest Oncology Group criteria) and changes in
      laboratory parameters. Cardiotoxicity was assessed with left ventricular ejection
      fraction (LVEF) mainly on MRI or echocardiography. RESULTS: The mean maximum
      postchemoembolization alanine transaminase increase in the DEB group was 50% less
      than in the conventional TACE group (p < 0.001) and 41% less in respect to
      aspartate transaminase (p < 0.001). End-of-study values returned to approximately
      baseline levels but with greater variability in conventional TACE patients.
      Treatment-emergent adverse events in the hepatobiliary system organ class
      occurred in 16.1% of DEB group patients compared with 25% of conventional TACE
      patients. There were fewer liver toxicity events in the DEB group. There was a
      small but statistically significant difference in mean change from baseline in
      LVEF between the two groups of 4 percentage points for the conventional TACE
      group (95% CI, 0.71-7.3; p = 0.018). CONCLUSION: PRECISION TACE with DEB loaded
      with doxorubicin offers a safe therapy option for intermediate-stage HCC, even in
      patients with more advanced liver disease.

PMID- 21940528
TI  - Percutaneous radiofrequency ablation for treatment of hepatocellular carcinoma in
      the caudate lobe.
AB  - OBJECTIVE: This study aimed to evaluate the efficacy and safety of percutaneous
      radiofrequency ablation (RFA) for the treatment of hepatocellular carcinoma (HCC)
      in the caudate lobe, where RFA is considered to be difficult. MATERIALS AND
      METHODS: Of a total of 810 patients treated by ultrasound-guided radiotherapy
      between July 2002 and May 2010, medical records of 50 consecutive patients with
      HCC in the caudate lobe were reviewed in this retrospective study. Twenty-two
      tumors were found to be in the paracaval portion and 28 in the Spiegel lobe. We
      retrospectively reviewed the procedures, treatment effect, and complications.
      RESULTS: For all paracaval tumors and eight Spiegel lobe tumors, we used the
      intercostal approach, and for the remaining Spiegel tumors (n = 20) we used the
      pass-the-left approach. We found that all tumors were successfully treated, and
      the local recurrence rate after 2 years was 12%. Cases of mortality or major
      complications after RFA were absent. CONCLUSION: RFA appears to be an effective
      treatment modality for HCC in the caudate lobe.

PMID- 21940529
TI  - Complications after 1000 lung radiofrequency ablation sessions in 420 patients: a
      single center's experiences.
AB  - OBJECTIVE: This study retrospectively evaluates complications after lung
      radiofrequency ablation (RFA). MATERIALS AND METHODS: Complications were assessed
      for each RFA session in 420 consecutive patients with 1403 lung tumors who
      underwent 1000 RFA sessions with a cool-tip RFA system. A major complication was
      defined as a grade 3 or 4 adverse event. Risk factors affecting frequent major
      complications that occurred with an incidence of 1% or more were detected using
      multivariate analysis. RESULTS: Four deaths (0.4% [4/1000]) related to RFA
      procedures occurred. Three patients died of interstitial pneumonia. The other
      patient died of hemothorax. The major complication rate was 9.8% (98/1000).
      Frequent major complications were aseptic pleuritis (2.3% [23/1000]), pneumonia
      (1.8% [18/1000]), lung abscess (1.6% [16/1000]), bleeding requiring blood
      transfusion (1.6% [16/1000]), pneumothorax requiring pleural sclerosis (1.6%
      [16/1000]), followed by bronchopleural fistula (0.4% [4/1000]), brachial nerve
      injury (0.3% [3/1000]), tumor seeding (0.1% [1/1000]), and diaphragm injury (0.1%
      [1/1000]). Puncture number (p < 0.02) and previous systemic chemotherapy (p <
      0.05) were significant risk factors for aseptic pleuritis. Previous external beam
      radiotherapy (p < 0.001) and age (p < 0.02) were significant risk factors for
      pneumonia, as were emphysema (p < 0.02) for lung abscess, and serum platelet
      count (p < 0.002) and tumor size (p < 0.02) for bleeding. Emphysema (p < 0.02)
      was a significant risk factor for pneumothorax requiring pleural sclerosis.
      CONCLUSION: Lung RFA is a relatively safe procedure, but it can be fatal. Risk
      factors found in this study will help to stratify high-risk patients.

PMID- 21940530
TI  - Ablation for the management of pulmonary malignancies.
AB  - OBJECTIVE: Surgical resection remains the treatment of choice for patients with
      early-stage primary lung cancer and selected patients with limited metastatic
      lung disease. However, surgery is a high-risk treatment for patients with
      coexisting morbidities, severe chronic obstructive pulmonary disease, a single
      lung, or a history of prior resection. The indications for and outcomes of
      ablative therapies performed for the management of pulmonary malignancies are
      discussed. CONCLUSION: Preservation of residual lung parenchyma when treating
      patients with early-stage primary lung cancer and those with limited metastatic
      lung disease is vital and can be achieved with image-guided thermal ablation
      therapies.

PMID- 21940531
TI  - Arterially directed therapies for hepatocellular carcinoma.
AB  - OBJECTIVE: Arterially directed therapies for hepatocellular carcinoma are used
      for patients who are not candidates for surgery or ablation and for those who
      need a bridge or down-staging to liver transplantation. These therapies seem to
      prolong the overall survival when compared with supportive care. CONCLUSION:
      Chemoembolization, particle embolization, drug-eluting beads, and
      radioembolization have been used for locoregional control. This review discusses
      patient selection, techniques, safety, clinical outcomes, and imaging findings
      related to these therapies.

PMID- 21940532
TI  - Cardiac MRI: Part 1, cardiovascular shunts.
AB  - OBJECTIVE: MRI plays an important role in the morphologic and functional
      evaluation of cardiovascular shunts. Good spatiotemporal resolution, inherent
      contrast resolution, wide FOV, and multiplanar imaging capabilities make MRI an
      ideal tool in the investigation of cardiovascular shunts. The velocity-encoded
      phase-contrast sequence is used in the quantification of a shunt and the steady
      state free precession (SSFP) sequence is used in the assessment of the functional
      impact of a shunt. In this article, the role of MRI in the evaluation of
      cardiovascular shunts and their respective MRI appearances are described and
      illustrated. CONCLUSION: MRI can identify and characterize septal defects,
      quantify shunts and their impact on cardiac function, and help in the selection
      of appropriate candidates for percutaneous device placement.

PMID- 21940533
TI  - Cardiac MRI: Part 2, pericardial diseases.
AB  - OBJECTIVE: MRI plays an important role in the morphologic and functional
      evaluation of pericardial diseases. MRI has the advantages of high spatiotemporal
      resolution, soft-tissue contrast, wide FOV, and multiplanar imaging capabilities,
      making it a valuable tool in the evaluation of pericardial disorders. In this
      article, the role of MRI in the evaluation of pericardial disorders, including
      pericardial constriction, is described and illustrated. CONCLUSION: MRI is a
      vital diagnostic tool in the evaluation of pericardial diseases, particularly
      inflammation and constriction, because it can provide both morphologic and
      functional information essential for determining the optimal therapeutic
      strategy. It is used for the characterization and delineation of the extent of
      spread of pericardial masses. Various imaging sequences are available, so the MRI
      protocol should be optimized and tailored to the specific clinical condition that
      is being evaluated.

PMID- 21940534
TI  - Atrial abnormalities: spectrum on MRI.
AB  - OBJECTIVE: The purpose of this article is to illustrate the MRI appearance of
      anatomic variations and congenital heart diseases that involve, directly or
      indirectly, the atria. CONCLUSION: Anatomic variants and congenital diseases
      involving the atria are characterized by a wide variety of MRI manifestations,
      most of which can be explained by the underlying pathophysiology and relationship
      to normal atrial anatomy.

PMID- 21940535
TI  - MRI findings of mediastinal neurogenic tumors.
AB  - OBJECTIVE: The objective of this article is to review the clinical, pathologic,
      and MRI findings of mediastinal neurogenic tumors according to the three tumor
      origins: the peripheral nerves, sympathetic ganglia, and paraganglia. CONCLUSION:
      MRI findings reflect pathologic features of mediastinal neurogenic tumors.
      Integrating consideration of age and clinical findings of the patient, lesion
      location, and imaging findings is important in the diagnosis of mediastinal
      neurogenic tumors.

PMID- 21940536
TI  - CT colonography in patients who have undergone sigmoid colostomy: a feasibility
      study.
AB  - OBJECTIVE: The purpose of this study was to evaluate the technical feasibility of
      CT colonography of patients who have undergone sigmoid colostomy after
      abdominoperineal resection. MATERIALS AND METHODS: Seven men and 11 women (mean
      age, 57.2 +/- 14.5 [SD] years) who had undergone abdominoperineal resection with
      sigmoid colostomy for rectal cancer were included. Colonic cleansing and fecal
      tagging were performed with magnesium citrate and 5% weight/volume barium. A
      conventional small rectal catheter with a retention balloon was introduced into
      the colonic stoma. An inflated balloon (15-25 mL) was positioned several
      centimeters beneath the skin. The interposed tissue acted as the mechanism for
      preventing balloon expulsion during colonic insufflation with carbon dioxide.
      Unenhanced right decubitus and contrast-enhanced supine images were obtained. Air
      fluid leak, balloon expulsion, complications, and colonic distention evaluated on
      a 4-point scale in which 1 was the worst and 4 the best and mucosal coverage were
      assessed. RESULTS: Examinations were performed uneventfully for all but one
      patient, who had temporary air and fluid leakage. The mean amount of carbon
      dioxide used was 2.64 +/- 0.64 L. In the right decubitus position, the mean
      distention grade of each colonic segment was 2.7 +/- 1.1 (sigmoid), 3.4 +/- 0.6
      (descending), 3.6 +/- 0.5 (transverse), 3.6 +/- 0.5 (ascending), and 3.7 +/- 0.5
      (cecum). In the supine position the mean grades were 2.7 +/- 1.2, 3.1 +/- 0.7,
      3.7 +/- 0.5, 3.7 +/- 0.5, and 3.8 +/- 0.4. Four patients (22.2%) had segments not
      adequately visualized in either position owing to luminal collapse; all of these
      segments were in the sigmoid colon. Three patients (16.7%) had areas submerged
      under fecal matter in both positions, but these areas were evaluable because of
      fecal tagging or IV contrast enhancement. CONCLUSION: CT colonographic
      examination through a sigmoid stoma was technically feasible with currently
      available instruments, but further improvements in technique are needed.

PMID- 21940537
TI  - Extrahepatic spread of hepatocellular carcinoma: spectrum of imaging findings.
AB  - OBJECTIVE: The purpose of this article is to describe the imaging findings of
      extrahepatic spread of hepatocellular carcinoma (HCC). CONCLUSION: Detecting
      extrahepatic metastases in HCC is critical in determining the optimal treatment
      plan for patients. Identifying the presence of extrahepatic metastases in
      patients with advanced disease may eliminate unnecessary surgery, such as liver
      transplantation or partial hepatic resection, and help direct the appropriate
      therapy.

PMID- 21940538
TI  - Heterogeneous type 4 enhancement of hepatocellular carcinoma on dynamic CT is
      associated with tumor recurrence after radiofrequency ablation.
AB  - OBJECTIVE: The aim of this study was to predict recurrence of hepatocellular
      carcinoma (HCC) from baseline dynamic CT images. MATERIALS AND METHODS: This
      retrospective study included 191 consecutive patients who underwent surgical
      resection or radiofrequency ablation (RFA) between January 2005 and September
      2009 for the treatment of HCC. Enhancement on pretreatment arterial and portal
      phase dynamic CT images was classified into one of the four following enhancement
      patterns: Types 1 and 2 are homogeneous enhancement patterns without or with
      increased arterial blood flow, respectively; type 3 is a heterogeneous
      enhancement pattern with septations; and type 4 is an irregularly shaped ring
      structure enhancement pattern. Predictive factors for tumor recurrence including
      dynamic CT enhancement pattern were also evaluated. Moreover, risk factors
      including recurrence type (i.e., tumor number >= 10, portal vein invasion, or
      both) were evaluated in RFA-treated cases. RESULTS: Among 60 patients who
      underwent surgical resection, no statistical association was observed between
      dynamic CT enhancement patterns and recurrence rate. In contrast, in the 131
      patients who underwent RFA, cumulative recurrence rates for each enhancement
      pattern were significantly different: Recurrence rates 2 years after RFA for
      patients with type 1, 2, 3, and 4 were 26.6%, 46.9%, 38.6%, and 77.8%,
      respectively (p = 0.042). Recurrence, which was defined as the presence of 10 or
      more nodules, portal vein invasion, or both occurred in nine of 131 patients
      (6.9%) in the RFA group. A multivariate Cox proportional hazards analysis
      revealed that the type 4 dynamic CT enhancement pattern is an independent factor
      for HCC recurrence (hazard ratio, 27.68; 95% CI, 6.82-112.33; p < 0.001).
      CONCLUSION: The pretreatment type 4 dynamic CT enhancement pattern can
      potentially be used to predict recurrence of HCC after RFA treatment.

PMID- 21940539
TI  - Is segmental enhancement inversion on enhanced biphasic MDCT a reliable sign for
      the noninvasive diagnosis of renal oncocytomas?
AB  - OBJECTIVE: The objective of our study was to retrospectively determine whether
      segmental enhancement inversion or other CT patterns seen at enhanced biphasic
      MDCT are predictive for the diagnosis of renal oncocytoma. MATERIALS AND METHODS:
      Twenty-nine patients with 32 oncocytomas diagnosed by either biopsy or resection
      who had undergone enhanced biphasic CT between January 2004 and March 2010 were
      included in this study. Biphasic CT scans were analyzed for the presence of
      segmental enhancement inversion. Segmental enhancement inversion was defined as a
      renal mass with two distinctive segments in which the attenuation of the segments
      changed between the two phases of CT. The masses were further characterized on
      imaging to determine if any imaging feature is predictive of renal oncocytoma.
      RESULTS: Of the 32 renal oncocytomas, 16 oncocytomas were eliminated from
      analysis. These masses were eliminated because they were larger than 4 cm (n =
      4), the CT examinations were inadequate (n = 10), or the pathology results were
      questionable (n = 2). The remaining 16 tumors (mean size, 2.6 cm; range, 1.8-3.9
      cm) were included in our study. Only two tumors showed distinct segments of
      variable degrees of enhancement, with one of those tumors having segmental
      enhancement inversion. Three masses had a central region of low density. The most
      common feature, identified in eight of the 16 oncocytomas, was a slightly
      heterogeneous mass that became homogeneous on the later phase of CT. Three
      oncocytomas had a homogeneous appearance on both phases. CONCLUSION: Contrary to
      a prior report, we did not find segmental enhancement inversion to be a
      characteristic enhancement pattern of small renal oncocytomas on biphasic MDCT.
      We found no specific features on biphasic CT that could be considered reliable
      and could strongly suggest the diagnosis of renal oncocytoma.

PMID- 21940540
TI  - Synchronous renal masses in patients with a nonrenal malignancy: incidence of
      metastasis to the kidney versus primary renal neoplasia and differentiating
      features on CT.
AB  - OBJECTIVE: The purpose of this study was to establish the contemporaneous
      frequency of metastases within the kidney as opposed to primary renal tumors in
      patients with an active primary nonrenal malignancy and to identify the
      differentiating features. MATERIALS AND METHODS: We retrospectively identified
      all patients with an active primary nonrenal malignancy (group 1) who had also
      undergone at least 2 contrast-enhanced abdominal CT examinations spaced 1 year
      apart. The radiologic and pathologic data of these cases were reviewed and the
      incidence of metastasis to the kidney versus primary renal tumors established.
      These data were compared with a separate group who presented with primary renal
      malignancy from the outset (group 2). RESULTS: In the study were 2340 patients
      with primary nonrenal malignancy (group 1) and 231 patients with a primary renal
      malignancy (group 2). For group 1, the mean age was 63 years and 51% were men;
      for group 2, the mean age was 59 years, and 58% were men. The differences were
      not statistically significant. Thirty-six patients in group 1 had a malignant
      renal mass; 21 were a result of kidney metastasis and the remaining 15 were a
      synchronous primary renal tumor (0.9% vs 0.6%). The kidney was the eighth most
      common site of metastatic spread. Metastases to the kidney were statistically
      more likely with higher tumor stage of the primary nonrenal malignancy (68% vs
      46%, p = 0.0006) and in those with other sites of metastasis (p = 0.012, positive
      likelihood ratio [LR+] = 6.75). Compared with primary renal tumors, metastases to
      the kidney were more often solid (86% vs 53%, p = 0.019, LR+ = 3.7) and
      endophytic (76% vs 33%, p = 0.017, LR+ = 2.29). There were too few cases with
      calcification and bilateral tumors to reach a statistically significant
      conclusion. Tumor size, polar predominance, and enhancement pattern were similar
      in the two groups. The primary renal tumors seen in group 1 versus group 2 were
      similar regarding age and sex distribution, cell type, median size, and tumor
      stage. CONCLUSION: Metastases to the kidney are uncommon in modern radiologic
      practice (0.9%, 21/2340 in this study), and a renal mass seen in a patient with
      nonrenal malignancy is nearly as likely to be an incidental primary renal tumor.
      Metastasis is more likely in those with higher tumor stage or if other viscera
      are also affected and is usually an asymptomatic, small, endophytic, and solid
      mass. If a renal mass seen in a patient with primary nonrenal malignancy proves
      to be a synchronous primary renal tumor, its cell type and stage will be similar
      to sporadic primary renal tumors.

PMID- 21940541
TI  - Radiologic appearance of hereditary adrenal and extraadrenal paraganglioma.
AB  - OBJECTIVE: There is a wide spectrum of established and emerging genetic mutations
      associated with intraadrenal and extraadrenal paragangliomas. In this review, we
      present the typical radiologic patterns of disease associated with six well
      characterized genetic mutations and discuss other inherited and nonfamilial
      syndromes currently under characterization. CONCLUSION: Contrary to previous
      understanding, recent genotype advances suggest that the majority of
      paragangliomas may be genetically predisposed.

PMID- 21940542
TI  - Using focused missed-case conferences to reduce discrepancies in musculoskeletal
      studies interpreted by residents on call.
AB  - OBJECTIVE: The purpose of this study is to determine whether focused missed-case
      conferences can significantly reduce the number of major discrepancies in
      musculoskeletal imaging studies interpreted by residents on call. MATERIALS AND
      METHODS: A review of major discrepancies in musculoskeletal conventional
      radiography imaging studies interpreted by radiology residents and fellows on
      call from July 2008 to July 2009 revealed 31 common and important musculoskeletal
      injuries missed or misinterpreted at our institution. These missed cases were
      presented during focused missed-case conferences from July through October 2009.
      Only residents attended missed-case conferences. RESULTS: Over the 12 months
      before the missed-case conferences, there were 55 resident major discrepancies
      and 25 fellow major discrepancies, representing 31 common and important missed
      musculoskeletal injuries. Over the 12 months after the missed-case conferences,
      there were 18 resident major discrepancies and 21 fellow major discrepancies
      involving these injuries. This corresponds to a 67% reduction in the number of
      resident major discrepancies involving the 31 musculoskeletal injuries covered
      during the missed-case conferences (chi-square p < 0.001). The overall major
      discrepancy rate for all musculoskeletal conventional radiography studies was
      1.19% for residents and 1.55% for fellows (not significant) before the missed
      case conferences and 0.87% for residents and 1.46% for fellows (p < 0.05) after
      the missed-case conferences. During this time, fellows missed more
      musculoskeletal injuries related to the topics discussed during missed-case
      conferences (16) compared with residents (8) although fellows read significantly
      fewer studies overall. This accounted for 0.49% of the 0.59% difference between
      residents and fellows. CONCLUSION: Focused missed-case conferences are an
      effective educational intervention to significantly reduce the number of major
      discrepancies in radiology resident interpretation of musculoskeletal imaging
      studies on call.

PMID- 21940544
TI  - Ultrasound of the shoulder: asymptomatic findings in men.
AB  - OBJECTIVE: The purpose of this study was to examine the range and prevalence of
      asymp tomatic findings at sonography of the shoulder. MATERIALS AND METHODS: The
      study sample comprised 51 consecutively enrolled subjects who had no symptoms in
      either shoulder. Ultrasound of one shoulder per patient was performed by a
      musculoskeletal sonographer according to a defined protocol that included imaging
      of the rotator cuff, tendon of the long head of the biceps brachii muscle,
      subacromial-subdeltoid bursa, acromioclavicular joint, and posterior labrum. The
      shoulder imaged was determined at random. The 51 scans were retrospectively
      analyzed by three fellowship-trained musculoskeletal radiologists in consensus,
      and pathologic findings were recorded. Subtle or questionable findings of mild
      tendinosis, bursal prominence, and mild osteoarthritis were not recorded.
      RESULTS: Twenty-five right and 26 left shoulders were imaged. The subject age
      range was 40-70 years. Ultrasound showed subacromial-subdeltoid bursal thickening
      in 78% (40/51) of the subjects, acromioclavicular joint osteoarthritis in 65%
      (33/51), supraspinatus tendinosis in 39% (20/51), subscapularis tendinosis in 25%
      (13/51), partial-thickness tear of the bursal side of the supraspinatus tendon in
      22% (11/51), and posterior glenoid labral abnormality in 14% (7/51). All other
      findings had a prevalence of 10% or less. CONCLUSION: Asymptomatic shoulder
      abnormalities were found in 96% of the subjects. The most common were subacromial
      subdeltoid bursal thickening, acromioclavicular joint osteoarthritis, and
      supraspinatus tendinosis. Ultrasound findings should be interpreted closely with
      clinical findings to determine the cause of symptoms.

PMID- 21940543
TI  - Quantitative radiology: automated CT liver volumetry compared with interactive
      volumetry and manual volumetry.
AB  - OBJECTIVE: The purpose of this study was to evaluate automated CT volumetry in
      the assessment of living-donor livers for transplant and to compare this
      technique with software-aided interactive volumetry and manual volumetry.
      MATERIALS AND METHODS: Hepatic CT scans of 18 consecutively registered
      prospective liver donors were obtained under a liver transplant protocol.
      Automated liver volumetry was developed on the basis of 3D active-contour
      segmentation. To establish reference standard liver volumes, a radiologist
      manually traced the contour of the liver on each CT slice. We compared the
      results obtained with automated and interactive volumetry with those obtained
      with the reference standard for this study, manual volumetry. RESULTS: The
      average interactive liver volume was 1553 +/- 343 cm(3), and the average
      automated liver volume was 1520 +/- 378 cm(3). The average manual volume was 1486
      +/- 343 cm(3). Both interactive and automated volumetric results had excellent
      agreement with manual volumetric results (intraclass correlation coefficients,
      0.96 and 0.94). The average user time for automated volumetry was 0.57 +/- 0.06
      min/case, whereas those for interactive and manual volumetry were 27.3 +/- 4.6
      and 39.4 +/- 5.5 min/case, the difference being statistically significant (p <
      0.05). CONCLUSION: Both interactive and automated volumetry are accurate for
      measuring liver volume with CT, but automated volumetry is substantially more
      efficient.

PMID- 21940545
TI  - Bone marrow edema patterns in the ankle and hindfoot: distinguishing MRI
      features.
AB  - OBJECTIVE: Many disorders produce similar or overlapping patterns of bone marrow
      edema in the ankle. Bone marrow edema may present in a few hindfoot bones
      simultaneously or in a single bone. The purpose of this pictorial essay is to
      provide guidelines based on clinical history and specific MRI patterns and
      locations to accurately identify the cause of ankle bone marrow edema. We will
      first focus on bone marrow edema in general disease categories involving multiple
      bones, such as reactive processes, trauma, neuroarthropathy, and arthritides. A
      discussion of bone marrow edema in individual bones of the ankle and hindfoot
      including the tibia, fibula, talus, and calcaneus will follow. Helpful hints for
      arriving at the correct diagnosis will be provided in each section. CONCLUSION:
      After review of this article, radiologists should be able to use their knowledge
      of clinical history and specific MRI patterns and locations to accurately
      distinguish between the various causes of bone marrow edema in the ankle and
      hindfoot.

PMID- 21940546
TI  - Tumor markers in fine-needle aspiration washout for cervical lymphadenopathy in
      patients with known malignancy: preliminary study.
AB  - OBJECTIVE: The purposes of our study were to assess whether tumor marker
      concentration in fine-needle aspiration (FNA) washout from cervical lymph nodes
      (LNs) differs between metastatic and nonmetastatic LNs and whether tumor marker
      concentrations in FNA washout can contribute to the diagnosis of metastatic LNs.
      SUBJECTS AND METHODS: Ultrasound-guided FNA was performed for 157 neck nodes in
      157 patients, including 136 patients with known malignancy (28 breast, 34 lung,
      41 head and neck, seven esophagus, nine cervix, 10 gastrointestinal [GI] tract,
      and seven ovary cancers) and 21 patients without known malignancy (control
      group). Immediately after an FNA cytology specimen was obtained, the needle was
      rinsed with 1 mL of normal saline solution, and variable tumor marker
      concentrations were measured in the washout: carcinoembryonic antigen (CEA) and
      cancer antigen (CA) 15-3 for breast; CEA and cytokeratin 19 fragment for lung;
      squamous cell antigen for head and neck, esophagus, and cervix; CEA and CA 19-9
      for GI; CA 125 for ovarian cancer; and all the tumor marker concentrations for
      the control group. The tumor marker concentration was compared between the
      metastatic and nonmetastatic LNs in the control group and between the metastatic
      and nonmetastatic LNs in the known malignancy group, according to the known
      malignancy. RESULTS: At final diagnosis, 104 LNs were metastatic and 53 were
      nonmetastatic (including 21 LNs in the control group). The tumor marker
      concentrations of cases with negative or nondiagnostic cytologic results were
      evaluated. The sensitivity of FNA cytology alone was compared with the combined
      sensitivity of FNA cytology and tumor marker concentration. Metastatic LNs had
      higher corresponding FNA tumor marker concentrations than did nonmetastatic LNs
      in both the control and known malignancy groups (p < 0.05), except for CA 19-9 in
      GI cancer. Eight of 10 cases (80%) with negative or nondiagnostic cytologic
      results but metastatic LNs at final diagnosis showed elevated tumor marker
      concentrations. The sensitivity of FNA cytology (90.4%) increased to 98.1% when
      combined with tumor marker concentration (p < 0.05). Tumor marker concentrations
      in FNA washout with cervical metastatic LNs were elevated in comparison with
      those of nonmetastatic LNs. CONCLUSION: Evaluation of tumor marker concentrations
      in FNA washout could improve the detection of metastatic LNs in patients with
      known malignancy.

PMID- 21940547
TI  - Compendium of national guidelines for imaging the pregnant patient.
AB  - OBJECTIVE: Diagnostic imaging performed during pregnancy, particularly if it
      involves the use of ionizing radiation, can be a source of great anxiety for both
      health care providers and patients. Especially with the growing public awareness
      of the increasing radiation from medical imaging, including CT, it is important
      to have a contemporary policy for imaging evaluation in the pregnant or
      potentially pregnant patient. Implementation of such policies and guidelines
      would be useful for those developing or modifying policies for imaging pregnant
      or potentially pregnant patients; those developing regional or national
      guidelines or recommendations (i.e., professional specialty societies, including
      emergency medicine, radiology, and obstetrics and gynecology); and groups such as
      National Council on Radiation Protection, advocacy groups, and individuals
      writing research grants or articles. CONCLUSION: To this end, a compendium of
      resources representing national organization guidelines would be useful. The
      purpose of this study is to review available resources for pertinent
      recommendations that can be used to develop or update policies for imaging during
      pregnancy, as well as to serve as a reference document for preparing reports,
      scientific articles, or other documents by individuals or organizations,
      including regulatory agencies.

PMID- 21940548
TI  - Ultrasound of fetal cardiac anomalies.
AB  - OBJECTIVE: Fetal cardiac anomalies are common, with half of them being lethal or
      requiring complex surgeries. Early detection of these anomalies enables early
      referral to tertiary care centers with adequate expertise. A routine antenatal
      ultrasound performed between 18 and 22 weeks enables detection of most of these
      malformations. Further comprehensive evaluation can be performed with a dedicated
      fetal echocardiography, particularly in high-risk pregnancies and in cases with
      extracardiac anomalies. CONCLUSION: Doppler imaging is used in the evaluation of
      vascular and valvular lesions. Three-dimensional imaging enables reconstruction
      of multiple complex planes from a single transverse acquisition. Four-dimensional
      imaging enables cine looping of images in multiple planes, enabling estimation of
      cardiac motion and function. This review illustrates the various sonographic
      techniques for evaluation of fetal hearts and the imaging appearance of various
      fetal cardiac anomalies.

PMID- 21940549
TI  - Detection of microcalcifications on digital screening mammograms using varying
      degrees of monitor zooming.
AB  - OBJECTIVE: The American College of Radiology recommends that mammogram images be
      viewed at 100% resolution (also called one-to-one or full resolution). We tested
      the effect of this and three other levels of zooming on the ability of
      radiologists to identify malignant calcifications on screening mammographic
      views. MATERIALS AND METHODS: Seven breast imagers viewed 77 mammographic images,
      32 with and 45 without malignant microcalcifications, using four different
      degrees of monitor zooming. The readers indicated whether they thought a cluster
      of potentially malignant calcifications was present and where the cluster was
      located. Tested degrees of zooming included fit screen, a size midway between fit
      screen and 100%, 100%, and a size slightly larger than 100%. RESULTS: Readers
      failed to detect 17 clusters of malignant calcifications with fit-screen images,
      12 clusters with midway images, 13 clusters with 100% images, and 11 clusters
      with slightly larger images. When viewing images without malignant
      microcalcifications, the readers marked false-positive areas on 25 images using
      fit-screen images, 43 of the midway images, 40 of the 100% images, and 29 of the
      slightly larger images. CONCLUSION: All four tested levels of zooming functioned
      well. There was a trend for the fit-screen images to function slightly less well
      than the others with regard to sensitivity, so it may not be prudent to rely on
      those images without other levels of zooming. The 100% resolution images did not
      function noticeably better than the others.

PMID- 21940550
TI  - MRI features of inflammatory breast cancer.
AB  - OBJECTIVE: The aim of this study was to evaluate the features of inflammatory
      breast carcinoma (IBC) on MRI compared with mammography and ultrasound and to
      better define the role of MRI in patients with this aggressive disease. MATERIALS
      AND METHODS: A retrospective analysis was performed of patients with newly
      diagnosed IBC evaluated at a single institution between 2003 and 2008. Baseline
      MRI examinations were performed on a 1.5- or 3-T scanner using contrast-enhanced
      3D T1-weighted gradient-echo sequences with parallel imaging. MRI findings were
      rated in accordance with the BI-RADS MRI lexicon established by the American
      College of Radiology. All patients underwent concomitant mammography and
      ultrasound examinations. RESULTS: Eighty women with a clinical diagnosis of IBC
      were included in the study (median age, 52 years; age range, 25-78 years). MRI
      detected a primary breast lesion in 78 of 80 symptomatic breasts (98%) compared
      with 53 of 78 (68%) with mammography (p < 0.0001) and 75 of 80 (94%) with
      ultrasound. Of the 78 breasts with a primary lesion, the most common MRI finding
      was a mass or multiple masses (57/78, 73%). Masses were frequently multiple,
      small, and confluent (47/57, 82%); mass margins, irregular (43/57, 75%); and
      internal enhancement pattern, heterogeneous (47/57, 82%). Kinetic analysis
      revealed a delayed washout pattern in 66 of 78 tumors (85%). MRI showed skin
      thickening in 74 of 80 breasts (93%), whereas mammography showed skin thickening
      in 56 of 78 breasts (72%). CONCLUSION: Multiple small, confluent, heterogeneously
      enhancing masses and global skin thickening are key MRI features of IBC that
      contribute to improved detection of a primary breast cancer and delineation of
      disease extent compared with mammography.

PMID- 21940551
TI  - Fluoroscopic procedures performed teleradiologically.

PMID- 21940552
TI  - Should residents provide after-hours radiology coverage?

PMID- 21940553
TI  - Training the next generation in luminal gastrointestinal radiology.

PMID- 21940554
TI  - Peak enhancement of the femoral head.

PMID- 21940555
TI  - Dual-energy CT: too many artifacts?

PMID- 21940556
TI  - Receiver operating characteristic analysis.

PMID- 21940557
TI  - Comparing health care systems internationally.

PMID- 21940558
TI  - Diagnosis of acute abdomen.

PMID- 21940559
TI  - Diverticula kissing vessel sign.

PMID- 21940560
TI  - Screening mammography, patient decision-making, and absolute risks.

PMID- 21940561
TI  - Response to Hendrick and Helvie by the Cancer Intervention Surveillance Modeling
      Network (CISNET) Breast Working Group.

PMID- 21940562
TI  - Evaluation of breast cancer screening strategies must be based on comparison of
      harms and benefits.

PMID- 21940563
TI  - Radiation dose exposure for lumbar spine epidural steroid injections: a
      comparison of conventional fluoroscopy data and CT fluoroscopy techniques.
AB  - OBJECTIVE: The purpose of this article is to compare the radiation dose of
      conventional fluoroscopy-guided lumbar epidural steroid injections (ESIs) and CT
      fluoroscopy (CTF)-guided lumbar ESI using both clinical data and anthropomorphic
      phantoms. MATERIALS AND METHODS: We performed a retrospective review of dose
      parameters for 14 conventional fluoroscopy ESI procedures performed by one
      proceduralist and 42 CTF-guided ESIs performed by three proceduralists (14 each).
      By use of imaging techniques similar to those for our clinical cohorts, a
      commercially available anthropomorphic male phantom with metal oxide
      semiconductor field effect transistor detectors was scanned to obtain absorbed
      organ doses for conventional fluoroscopy-guided and CTF-guided ESIs. Effective
      dose (ED) was calculated from measured organ doses. RESULTS: The mean
      conventional fluoroscopy time for ESI was 37 seconds, and the mean procedural CTF
      time was 4.7 seconds. Calculated ED for conventional fluoroscopy was 0.85 mSv
      compared with 0.45 mSv for CTF. The greatest contribution to the radiation dose
      from CTF-guided ESI came from the planning lumbar spine CT scan, which had an ED
      of 2.90 mSv when z-axis ranged from L2 to S1. This resulted in a total ED for CTF
      guided ESI (lumbar spine CT scan plus CTF) of 3.35 mSv. CONCLUSION: The ED for
      the CTF-guided ESI was almost half that of conventional fluoroscopy because of
      the shorter fluoroscopy time. However, the overall radiation dose for CTF-guided
      ESIs can be up to four times higher when a full diagnostic lumbar CT scan is
      performed as part of the procedure. Radiation dose reduction for CTF-guided ESI
      is best achieved by minimizing the dose from the preliminary planning lumbar
      spine CT scan.

PMID- 21940564
TI  - CT-guided lung biopsies: pleural blood patching reduces the rate of chest tube
      placement for postbiopsy pneumothorax.
AB  - OBJECTIVE: The objective of our study was to determine whether pleural blood
      patching reduces the need for chest tube placement and hospital admission for
      pneumothorax complicating CT-guided percutaneous lung biopsy. MATERIALS AND
      METHODS: We reviewed 463 CT-guided lung biopsies performed between August 2006
      and March 2010 to determine whether intervention for pneumothorax was required
      and patient outcome. Intervention was categorized as simple aspiration,
      aspiration and intrapleural blood patching, or chest tube placement and hospital
      admission. The technique for pleural blood patching consisted of complete
      pneumothorax aspiration, immediate placement of up to 15 mL of peripheral
      autologous blood into the pleural space, and positioning the patient in the
      ipsilateral decubitus position for 1 hour after the procedure. RESULTS:
      Intervention for pneumothorax was necessary in 45 of 463 patients (9.7%) and 19
      of 463 patients (4.1%) required chest tube placement. Pleural blood patching as a
      method to treat a postbiopsy pneumothorax and avoid further intervention was
      associated with a significantly higher success rate than simple aspiration: 19 of
      22 (86.4%) vs seven of 15 (46.7%) (odds ratio = 7.2, p = 0.03), respectively.
      CONCLUSION: Aspiration with intrapleural blood patching is superior to simple
      aspiration to treat pneumothorax associated with CT-guided lung biopsy. Pleural
      blood patching reduces the need for chest tube placement and hospital admission
      in this patient population.

PMID- 21940565
TI  - Percutaneous tumor ablation for hepatocellular carcinoma.
AB  - OBJECTIVE: This report reviews the current clinical status of percutaneous
      ablation of hepatocellular carcinoma (HCC). CONCLUSION: HCC is increasing in
      incidence. Multiple percutaneous ablation methods are now available for primary
      treatment or for bridging to transplantation. Percutaneous ethanol instillation
      and radiofrequency ablation are the most extensively evaluated percutaneous
      treatments for HCC. Newer technologies are being evaluated and may change future
      practice patterns.

PMID- 21940566
TI  - Percutaneous biliary metallic stent placement in patients with unilobar portal
      vein occlusion caused by advanced hilar malignancy: outcome of unilateral versus
      bilateral stenting.
AB  - OBJECTIVE: The purpose of this study was to investigate the outcome of biliary
      metallic stent placement in patients with contralateral portal vein occlusion
      caused by advanced hilar malignancy and to compare the outcomes of unilateral and
      bilateral stent placement. MATERIALS AND METHODS: From January 2007 to December
      2009, 41 patients with unilobar portal vein occlusion due to advanced hilar
      malignancy were enrolled in this retrospective study. All patients were treated
      with percutaneous placement of biliary metallic stents: unilateral stent
      placement in 23 patients, bilateral stent placement in 18 patients. RESULTS:
      There were no significant differences in technical success (p > 0.999),
      successful drainage (p > 0.999), early cholangitis (p = 0.734), stent occlusion
      (p = 0.713), stent patency (p = 0.653), or patient survival (p = 0.493) between
      the two groups. In the patients who underwent unilateral stent placement, a
      slight decrease in diameter (mean diameter, 7.2 +/- 3 mm before drainage, 6.2 +/-
      3 mm after stent placement) (p = 0.058) was observed in the intrahepatic bile
      duct of the undrained lobe with portal vein occlusion. Four of the patients who
      underwent unilateral stent placement had stent malfunctions, but the other 19
      patients did not experience cholangitis or jaundice before death or the end of
      the study. CONCLUSION: Unilateral biliary metallic stent placement in the lobe
      with a patent portal vein seems to be a safe and effective palliative treatment
      of patients with contralateral portal vein occlusion caused by advanced hilar
      malignancy, obviating bilateral stent placement in these patients.

PMID- 21940567
TI  - Cardiac imaging: Part 1, MR pulse sequences, imaging planes, and basic anatomy.
AB  - OBJECTIVE: MRI is a well-established modality for evaluating congenital and
      acquired cardiac diseases. This article reviews the latest pulse sequences used
      for cardiac MRI. In addition, the standard cardiac imaging planes and
      corresponding anatomy are described and illustrated. CONCLUSION: Familiarity with
      the basic pulse sequences, imaging planes, and anatomy pertaining to cardiac MRI
      is essential to formulate optimal protocols and interpretations.

PMID- 21940568
TI  - Cardiac imaging: Part 2, normal, variant, and anomalous configurations of the
      coronary vasculature.
AB  - OBJECTIVE: Noninvasive imaging of the heart and coronary vasculature using CT and
      MRI is a new and exciting opportunity for radiologists. The purpose of this
      pictorial essay is to review normal and variant anatomy of the coronary arteries
      and of several coronary anomalies that may be clinically significant. The
      coronary veins and artifacts simulating disease will also be briefly covered.
      This article will help radiologists learn and review normal coronary anatomy,
      normal variants, and coronary anomalies and recognize pitfalls, such as coronary
      veins and artifacts, that may be confusing when first encountered. CONCLUSION:
      The coronary arteries generally are predictable in their origin, course, and
      perfusion territories. Standardized reporting systems exist for describing the
      location of specific lesions, and radiologists who interpret CT and MR coronary
      images should be aware of and should attempt to integrate these reporting schemes
      into clinical practice.

PMID- 21940570
TI  - Vascular enhancement and image quality of CT venography: comparison of standard
      and low kilovoltage settings.
AB  - OBJECTIVE: The objective of our study was to investigate the vascular enhancement
      and image quality of CT venography (CTV) with a lower peak kilovoltage (kVp)
      setting than the standard setting. MATERIALS AND METHODS: In this retrospective
      study, the clinical records of 100 consecutive patients with suspected pulmonary
      embolism were analyzed. All patients underwent pulmonary CT angiography and CTV
      of the abdomen, pelvis, and lower extremities using 64-MDCT with automatic tube
      current modulation: 50 patients underwent CT at 120 kVp, the standard kVp
      setting, and 50 patients were scanned at 100 kVp; we refer to these groups as the
      "standard-kVp group" and the "low-kVp group," respectively. Vessel enhancement
      and image noise were assessed in the inferior vena cava (IVC), femoral vein, and
      popliteal vein. Two radiologists who were blinded to the kVp setting placed the
      regions of interest on vessels by consensus and assessed image quality using a 5
      point visual scale. Effective dose was estimated using the dose-length product.
      The Wilcoxon rank test was used to evaluate differences between the two groups
      using statistics software (JMP, version 5.1). A p value of less than 0.05 was
      considered to indicate statistical significance. RESULTS: Mean vascular
      enhancement was significantly higher in the low-kVp group than in the standard
      kVp group: IVC, 138.4 +/- 12.2 (SD) HU versus 164.5 +/- 17.4 HU, respectively;
      femoral vein, 130.2 +/- 18.0 HU versus 152.0 +/- 24.5 HU; and popliteal vein,
      136.7 +/- 17.5 HU versus 158.3 +/- 26.0 HU. Although the images of the low-kVp
      group had significantly higher image noise, there were no significant differences
      in image quality in the IVC and popliteal vein. The mean effective dose for the
      low-kVp protocol was significantly lower than that for the standard-kVp protocol.
      CONCLUSION: Lowering the kVp setting for CTV examinations improved vascular
      enhancement while providing sufficient image quality.

PMID- 21940569
TI  - Diagnostic performance of combined noninvasive coronary angiography and
      myocardial perfusion imaging using 320-MDCT: the CT angiography and perfusion
      methods of the CORE320 multicenter multinational diagnostic study.
AB  - OBJECTIVE: Coronary MDCT angiography has been shown to be an accurate noninvasive
      tool for the diagnosis of obstructive coronary artery disease (CAD). Its
      sensitivity and negative predictive value for diagnosing percentage of stenosis
      are unsurpassed compared with those of other noninvasive testing methods.
      However, in its current form, it provides no information regarding the
      physiologic impact of CAD and is a poor predictor of myocardial ischemia. CORE320
      is a multicenter multinational diagnostic study with the primary objective to
      evaluate the diagnostic accuracy of 320-MDCT for detecting coronary artery
      luminal stenosis and corresponding myocardial perfusion deficits in patients with
      suspected CAD compared with the reference standard of conventional coronary
      angiography and SPECT myocardial perfusion imaging. CONCLUSION: We aim to
      describe the CT acquisition, reconstruction, and analysis methods of the CORE320
      study.

PMID- 21940571
TI  - Coronary enhancement for prospective ECG-gated single R-R axial 320-MDCT
      angiography: comparison of 60- and 80-mL iopamidol 370 injection.
AB  - OBJECTIVE: The objective of our study was to evaluate the difference in coronary
      enhancement provided by 60 versus 80 mL of contrast medium (370 mg I/mL) for
      prospectively ECG-gated single-heartbeat axial 320-MDCT. MATERIALS AND METHODS:
      We retrospectively evaluated 108 consecutive 320-MDCT angiography studies. Group
      1 (n = 36) received 60 mL of an iodinated contrast medium and group 2 (n = 72),
      80 mL. All patients were imaged with a standardized protocol: iopamidol 370
      followed by 40 mL of saline, both administered at a rate of 6 mL/s. Two imagers
      subjectively assessed image quality throughout the coronary arteries. Region-of
      interest attenuation (HU) measurements were performed in the aorta plus the
      proximal and distal coronary arteries. RESULTS: Subjective analysis of all
      coronary segments showed slightly better image quality for group 2. Patients in
      group 1 had significantly (p < 0.05) lower mean attenuation values for the
      individual coronary vessels. Nevertheless, 96.7% of all coronary segments in the
      group 1 patients had an attenuation of greater than 300 HU; when analysis was
      limited to group 1 patients with a body mass index of greater than 30, 92.8% of
      the segments were more than 300 HU, and all segments measured more than 250 HU.
      CONCLUSION: An injection protocol based on 60 mL of iopamidol (370 mg I/mL) for
      prospectively ECG-gated wide-area detector single-heartbeat coronary CT
      angiography (CTA) has less coronary enhancement than a protocol based on 80 mL.
      However, using 60 mL, more than 96% of coronary segments had sufficient
      enhancement (i.e., > 300 HU), supporting the general use of 60-mL protocols for
      clinical wide-area detector coronary CTA.

PMID- 21940572
TI  - Predictors of image quality in high-pitch coronary CT angiography.
AB  - OBJECTIVE: High-pitch coronary CT angiography (CTA) shows an alternative coronary
      CTA protocol to retrospectively ECG-gated imaging that is associated with a
      significantly lower radiation exposure. Yet, the diagnostic quality of high-pitch
      coronary CTA cannot be sufficiently predicted on the basis of heart rate (HR)
      alone. Thus, we sought to prospectively identify the predictors of diagnostic
      high-pitch coronary CTA. SUBJECTS AND METHODS: One hundred consecutive patients
      (16 women, 84 men; mean age, 67 +/- 10 years) without restrictions in HR
      frequency or variability underwent prospectively ECG-gated high-pitch coronary
      artery calcification (CAC) scoring and coronary CTA using dual-source 128-MDCT.
      High-pitch CAC was graded on the basis of motion artifacts; high-pitch coronary
      CTA was graded on the basis of image quality by each of two independent and
      blinded readers. Predictors of coronary CTA image quality were assessed by
      multivariate logistic regression, including body mass index, risk of coronary
      artery disease, Agatston score, HR frequency and variability, and motion
      artifacts on CAC. If high-pitch coronary CTA was nondiagnostic, the examination
      was repeated using a retrospectively ECG-gated coronary CTA protocol. RESULTS: HR
      frequency (66 +/- 20 beats per minute [bpm]) and variability (12 +/- 10 bpm)
      during high-pitch coronary CTA was not significantly different from that during
      high-pitch CAC. Interobserver agreement for image quality reading was good (k =
      0.79) for CAC and excellent (k = 0.88) for coronary CTA. High-pitch CAC showed no
      motion artifacts in 1304 of 1396 segments (93.4%) in 78 of 100 patients.
      Diagnostic image quality of high-pitch coronary CTA was found in 1413 of 1457
      segments (97%) in 82 of 100 patients. Multivariate logistic regression revealed
      HR frequency (odds ratio, 1.04; p < 0.05) and motion artifacts on preceding high
      pitch CAC (odds ratio, 94.55; p < 0.001) as significant independent predictors of
      image quality of high-pitch coronary CTA. The mean effective radiation doses of
      high-pitch CAC and coronary CTA were 0.4 +/- 0.1 mSv (0.3-0.5 mSv) and 1.0 +/-
      0.2 mSv (0.8-1.2 mSv; p < 0.001), respectively. CONCLUSION: HR frequency and
      motion artifacts on preceding high-pitch CAC represent significant independent
      predictors of image quality in high-pitch coronary CTA.

PMID- 21940573
TI  - The negative appendectomy rate: who benefits from preoperative CT?
AB  - OBJECTIVE: The purpose of this article is to determine the negative appendectomy
      rates of patients who did and did not undergo preoperative CT and to determine,
      more specifically, whether men benefit from preoperative CT. MATERIALS AND
      METHODS: We identified 512 patients who had a nonincidental appendectomy between
      July 1, 2002, and June 30, 2007. Pathology records were compared with a radiology
      records search to determine which patients underwent preoperative CT. Proportions
      of patients were compared between groups using the Fisher exact test. RESULTS: Of
      512 patients who had a nonincidental appendectomy, 465 (91%) underwent
      preoperative CT, and 47 (9%) underwent appendectomy only on the basis of clinical
      findings. Overall, 22 of 465 patients (4.7%) who underwent preoperative CT had a
      negative appendectomy compared with six of 47 patients who did not undergo
      preoperative imaging (negative appendectomy rate, 12.7%; p = 0.03). Among men,
      six of 237 (2.5%) with preoperative CT had a negative appendectomy, versus five
      of 42 without imaging (negative appendectomy rate, 11.9%; p = 0.01). CONCLUSION:
      The negative appendectomy rate was decreased for adult patients who underwent
      preoperative CT compared with patients who did not undergo preoperative imaging.
      Although most prior studies have suggested that CT is efficacious only in
      decreasing the negative appendectomy rate among women, we found that men benefit
      from CT as well.

PMID- 21940574
TI  - Diagnosis of the invasion depth of gastric cancer using MDCT with virtual
      gastroscopy: comparison with staging with endoscopic ultrasound.
AB  - OBJECTIVE: The objectives of this study were to retrospectively evaluate the
      lesion detection rate of gastric cancer using only virtual gastroscopy generated
      from MDCT images and the accuracy of invasion depth diagnosis (T staging) using
      virtual gastroscopy together with contrast-enhanced MDCT with multiplanar
      reconstruction (MPR) images (virtual gastroscopy with MPR), and to compare the
      diagnostic performance between virtual gastroscopy with MPR images and endoscopic
      ultrasound. MATERIALS AND METHODS: The subjects consisted of 175 patients with a
      total of 186 endoscopically proven gastric cancer lesions. All patients underwent
      dynamic MDCT (arterial and venous phase) for preoperative staging and underwent
      surgery or endoscopic treatment. In 129 patients (135 lesions) who were also
      examined using endoscopic ultrasound, the T staging accuracy was also compared
      between the two modalities. Two endoscopists independently evaluated the lesion
      detection rate on virtual gastroscopy images alone and determined the T stage on
      virtual gastroscopy with MPR images. The T staging included the ability to
      differentiate T1a from T1b lesions. RESULTS: The overall lesion detection rate
      was 67.7% (126/186). The detection rates of T1a, T1b, and T2 or deeper were 37.8%
      (28/74), 75.0% (39/52), and 98.3% (59/60), respectively, showing statistically
      significant differences (p < 0.001). The T staging accuracies were 82.2%
      (111/135) using virtual gastroscopy with MPR images and 83.7% (113/135) using
      endoscopic ultrasound, showing no statistically significant difference (p =
      0.850). The main causes of over- and understaging were an ulcer or ulcer scar and
      poorly differentiated adenocarcinomas, non-solid type, respectively. CONCLUSION:
      Virtual gastroscopy with MPR imaging is a useful modality in the T staging of
      gastric cancer.

PMID- 21940575
TI  - Quantitative color mapping of the arterial enhancement fraction in patients with
      diffuse liver disease.
AB  - OBJECTIVE: The purpose of this study was to determine whether color mapping of
      the arterial enhancement fraction of the liver with multiphasic liver CT can
      depict the hemodynamic changes associated with diffuse liver disease. MATERIALS
      AND METHODS: A total of 142 patients (59 men, 83 women; mean age, 50 years) with
      diffuse liver disease and 25 patients acting as controls (11 men, 14 women; mean
      age, 54 years) were classified into three groups: controls (n = 25), patients
      with acute liver injury (no underlying chronic liver disease [n = 25], acute
      exacerbation of chronic liver disease [n = 17]), and patients with chronic
      hepatic injury (hepatitis [n = 25]; cirrhosis [n = 75], 25 each with Child-Pugh
      A, B, and C disease). The quantitative arterial enhancement fraction color map of
      the liver was generated from routine multiphasic CT images with prototype
      software. The mean arterial enhancement fractions of each group were compared by
      analysis of variance. The correlation between arterial enhancement fraction and
      Child-Pugh grade was evaluated with Spearman correlation. The area under the
      receiver operating characteristic curve for arterial enhancement fraction in the
      detection of acute liver injury and noncompensated chronic liver disease was
      calculated. RESULTS: The mean arterial enhancement fractions of the liver in each
      group were significantly different (p < 0.0001, analysis of variance): control,
      28.5%; acute liver injury without underlying chronic liver disease, 51.1%; acute
      exacerbation of chronic liver disease, 42.0%; chronic hepatitis, 25.4%; Child
      Pugh A disease, 23.7%; Child-Pugh B disease, 32.2%; Child-Pugh C disease, 43.4%.
      Arterial enhancement fraction correlated with Child-Pugh grade (Spearman rho =
      0.553, p < 0.0001). The areas under the curve of arterial enhancement fraction in
      the detection of acute liver injury and noncompensated chronic liver disease were
      0.96 and 0.78. CONCLUSION: With color mapping of the arterial enhancement
      fraction derived from multiphasic liver CT scans, it is possible to visualize the
      hemodynamic changes associated with the severity of cirrhosis and acute liver
      injury.

PMID- 21940576
TI  - Characterization of small solid renal lesions: can benign and malignant tumors be
      differentiated with CT?
AB  - OBJECTIVE: The purpose of this study was to evaluate the diagnostic performance
      of CT in determining whether a small solid renal enhancing mass is benign or
      malignant. MATERIALS AND METHODS: Ninety-nine biopsies of enhancing solid renal
      masses 4 cm or smaller without fat on CT scans were performed under CT
      fluoroscopic guidance. The growth pattern, interface with parenchyma, presence of
      a scar and segmental inversion enhancement, unenhanced CT histogram, and pattern
      and degree of enhancement on triphasic MDCT images were independently evaluated
      by two radiologists. Biopsy and pathology reports were used as the reference
      standard, and imaging follow-up of benign lesions was performed for at least 1
      year. Statistical analysis was performed to determine the significance of CT
      criteria in differentiating malignant from benign lesions. RESULTS: Of the 99
      lesions, 74 (75%) were malignant at biopsy, and 25 (25%) were benign. Lesions
      with gradual enhancement were more likely to be benign. No significant
      correlation was found between other CT features and a malignant or benign
      diagnosis. The sensitivity, specificity, and positive and negative predictive
      values of progressive enhancement for a diagnosis of benignity were 60%, 73%,
      43%, and 84%. CONCLUSION: In the evaluation of enhancing small solid renal
      lesions without fat, no CT criteria were of substantial help in differentiating
      malignant from benign lesions.

PMID- 21940577
TI  - Evaluation of renal masses with contrast-enhanced ultrasound: initial experience.
AB  - OBJECTIVE: Nearly 25% of solid renal tumors are indolent cancer or benign and can
      be managed conservatively in selected patients. This prospective study was
      performed to determine whether preoperative IV microbubble contrast-enhanced
      ultrasound can be used to differentiate indolent and benign renal tumors from
      more aggressive clear cell carcinoma. SUBJECTS AND METHODS: Thirty-four patients
      with renal tumors underwent preoperative gray-scale, color, power Doppler, and
      octafluoropropane microbubble IV contrast-enhanced ultrasound. Three blinded
      radiologists reading in consensus compared rate of contrast wash-in, grade and
      pattern of enhancement, and contrast washout compared with adjacent parenchyma.
      Contrast ultrasound findings were compared with surgical histopathologic findings
      for all patients. RESULTS: The 34 patients had 23 clear cell carcinomas, three
      type 1 papillary carcinomas, one chromophobe carcinoma, one clear rare
      multilocular low-grade malignant tumor, two unclassified lesions, three
      oncocytomas, and one benign angiomyolipoma. The combination of heterogeneous
      lesion echotexture and delayed lesion washout had 85% positive predictive value,
      43% negative predictive value, 48% sensitivity, and 82% specificity for
      predicting whether a lesion was conventional clear cell carcinoma or another
      tumor. Diminished lesion enhancement grade had 75% positive predictive value, 81%
      negative predictive value, 55% sensitivity, and 91% specificity for non-clear
      cell histologic features, either benign or low-grade malignant. Combining delayed
      washout with quantitative lesion peak intensity of at least 20% of kidney peak
      intensity had 91% positive predictive value, 40% negative predictive value, 63%
      sensitivity, and 80% specificity in the prediction of clear cell histologic
      features. CONCLUSION: Ultrasound features of gray-scale heterogeneity, lesion
      washout, grade of contrast enhancement, and quantitative measure of peak
      intensity may be useful for differentiating clear cell carcinoma and non-clear
      cell renal tumors.

PMID- 21940578
TI  - Dynamic gadolinium-enhanced perfusion MRI of prostate cancer: assessment of
      response to hypofractionated robotic stereotactic body radiation therapy.
AB  - OBJECTIVE: The purpose of this study was to evaluate the utility of dynamic
      gadolinium-enhanced perfusion MRI for monitoring the response to robotic
      stereotactic body radiation therapy for prostate cancer. MATERIALS AND METHODS:
      Eighty-seven patients with prostate cancer underwent dynamic gadolinium-enhanced
      MRI before robotic stereotactic body radiation therapy, and prostate volume was
      calculated. Pharmacokinetic analysis postprocessing software was used to generate
      colorized parametric maps showing perfusion of enhancing tumors. The transfer
      constant K(trans) was calculated for identified tumors. Follow-up MRI was
      performed 2 months after treatment for 22 patients, 6 months for 71 patients, 12
      months for 54 patients, and 24 months for 27 patients with repeated measurements
      of prostate volume and K(trans). RESULTS: Perfusion MRI depicted focal enhancing
      prostate tumors that correlated with the biopsy results in 82 of 87 patients
      (94%). The median K(trans) of tumors before robotic stereotactic body radiation
      therapy was 1.79 minutes(-1). Follow-up MRI showed decreases in the size and
      degree of enhancement of tumors. The median tumor K(trans) decreased to 1.21
      minutes(-1) 2 months, 0.39 minutes(-1) 6 months, 0.30 minutes(-1) 12 months, and
      0.22 minutes(-1) 24 months after treatment. Prostate volume had decreased 23% 2
      months, 26% 6 months, 33% 12 months, and 37% 24 months after robotic stereotactic
      body radiation therapy. The corresponding median prostate-specific antigen
      concentration before treatment was 6.45 ng/mL. After treatment, the concentration
      was 2.90 ng/mL at 2 months, 1.30 ng/mL at 6 months, 1.10 ng/mL at 12 months, and
      0.59 ng/mL at 24 months. CONCLUSION: Dynamic gadolinium-enhanced MRI is a useful
      tool for monitoring the response of prostate cancer to robotic stereotactic body
      radiation therapy, yielding both qualitative and quantitative data.

PMID- 21940579
TI  - What is the role of the radiologist in holding down health care cost growth?

PMID- 21940580
TI  - Error rates in breast imaging reports: comparison of automatic speech recognition
      and dictation transcription.
AB  - OBJECTIVE: The purpose of this study was to compare the error rates in breast
      imaging reports generated with automated speech recognition (ASR) technology as
      opposed to conventional dictation transcription. MATERIALS AND METHODS: Breast
      imaging reports reviewed from January 2009 to April 2010 during multidisciplinary
      tumor board meetings at two hospitals were scrutinized for minor and major
      errors. RESULTS: Of 615 reports obtained, 308 were generated with ASR and 307
      with conventional dictation transcription. At least one major error was found in
      23% of ASR reports, as opposed to 4% of conventional dictation transcription
      reports (p < 0.01). Major errors were more common in breast MRI reports (35% of
      ASR and 7% of conventional reports), the lowest error rates occurring in reports
      of interventional procedures (13% of ASR and 4% of conventional reports) and
      mammography reports (15% of ASR and no conventional reports) (p < 0.01). The
      error rates did not differ substantially between reports generated by staff
      radiologists and trainees or between reports generated by speakers who spoke
      English as their first language and those whose native language was not English.
      After adjustment for academic rank, native language, and imaging modality,
      reports generated with ASR were 8 times as likely as conventional dictation
      transcription reports to contain major errors (p < 0.01). CONCLUSION: Reports
      generated with ASR are associated with higher error rates than reports generated
      with conventional dictation transcription. The imaging modality used is a
      predictor of the occurrence of reporting errors. Conversely, native language and
      academic rank of the speaker do not have a significant influence on error rate.

PMID- 21940581
TI  - Female breast, lung, and pelvic organ radiation from dose-reduced 64-MDCT
      thoracic examination protocols: a phantom study.
AB  - OBJECTIVE: We compared phantom organ doses delivered to breast, lung, and pelvis
      by five protocols using current dose reduction methods for routine chest CT and
      pulmonary CT angiography. MATERIALS AND METHODS: We measured the radiation dose
      to an anthropomorphic phantom using 64-MDCT with metal oxide semiconductor field
      effect transistor (MOSFET) detectors in the breast (skin and parenchyma), the
      lungs, and the pelvis (upper and lower). We compared the following five
      protocols: protocol 1, 120 kVp, automatic dose modulation, 120-320 mA; protocol
      2, 120 kVp, automatic dose modulation, 60-200 mA; protocol 3, 100 kVp and fixed
      dose of 200 mA; protocol 4, 120 kVp, automatic dose modulation, 200-394 mA; and
      protocol 5, 80 kVp and fixed dose of 120 mA. Organ doses in milligrays and as a
      percentage of the volume CT dose index (CTDI(vol)) were compared using the
      analysis of variance for repeated measurements. RESULTS: Protocol 1 delivered the
      highest breast dose (mean +/- SD, 15.8 +/- 1.8 mGy; 110.5% of CTDI(vol)). A
      decrease in breast radiation of more than 50% was achieved with protocol 3 (4.8
      +/- 1.8 mGy; 91.7% of CTDI(vol)) compared with protocol 4 (13.1 +/- 5.5 mGy;
      87.0% of CTDI(vol)) (p = 0.003). The lung received the highest organ dose
      regardless of the protocol (protocol 4: 21.5 +/- 1.7 mGy; 142.5% of CTDI(vol)).
      Pelvic radiation was low regardless of protocol and did not exceed 0.2 mGy (up to
      3.7% of CTDI(vol); p = 0.118-0.999). CONCLUSION: The results of this
      anthropomorphic phantom study showed substantial and significant variation in
      radiation doses to the breast and lungs depending on the scanning protocol used
      with the potential for over threefold dose reduction.

PMID- 21940582
TI  - A comprehensive approach to CT radiation dose reduction: one institution's
      experience.
AB  - OBJECTIVE: The purpose of this article is to review the process of creating and
      implementing a comprehensive plan to reduce diagnostic radiation exposure at our
      institution. CONCLUSION: This process, which was initiated by forming a radiation
      dose reduction committee, addressed several different issues to improve patient
      safety. These include avoidance of unnecessary CT examinations, adjusting
      individual scanning parameters, revising protocols, use of shielding and dose
      monitoring, and implementing computer-based dose modulation software as well as
      educating referring physicians and radiologic technologists.

PMID- 21940583
TI  - Long head of biceps brachii tendon evaluation: accuracy of preoperative
      ultrasound.
AB  - OBJECTIVE: The purpose of this study was to investigate the ability of ultrasound
      to accurately identify long head of biceps brachii (LHB) tendon abnormalities.
      MATERIALS AND METHODS: The surgical findings for 66 consecutive patients who
      underwent arthroscopic shoulder surgery were retrospectively compared with the
      findings of preoperative ultrasound examination. Patients were excluded if more
      than 200 days elapsed between ultrasound and surgery. Ultrasound images were
      obtained using high-frequency transducers and were compared with findings at
      arthroscopy for the presence of LHB tendon abnormalities, including full
      thickness tears, partial-thickness tears, or nontear abnormalities, including
      tendinosis and tenosynovitis. Sensitivity, specificity, positive predictive value
      (PPV), negative predictive value (NPV), and accuracy were calculated for full-
      and partial-thickness tears. RESULTS: Ultrasound correctly identified 90% (35/39)
      of normal LHB tendons, 88% (7/8) of full-thickness tears, 27% (3/11) of partial
      thickness tears, and 22% (2/9) of tendons with nontear abnormality in those
      patients who underwent surgery. In the ultrasound diagnosis of full-thickness
      tear versus other findings, sensitivity was 0.88, specificity was 0.98, PPV was
      0.88, NPV was 0.98, and accuracy was 0.97; in the ultrasound diagnosis of partial
      thickness tear versus other findings, sensitivity was 0.27, specificity was 1.00,
      PPV was 1.00, NPV was 0.88, and accuracy was 0.88, in those patients who
      underwent surgery. CONCLUSION: Shoulder ultrasound is an accurate method to
      confirm a normal biceps tendon or full-thickness tear, but is less accurate in
      the diagnosis of partial-thickness tear and nontear abnormalities.

PMID- 21940584
TI  - Fluoroscopically guided diagnostic and therapeutic injections into foot
      articulations: report of short-term patient responses and comparison of outcomes
      between various injection sites.
AB  - OBJECTIVE: A few studies have reported on short-term outcomes of patients
      receiving imaging-guided injections into the foot articulations, but none have
      compared patient responses depending on the anatomic site injected. This study
      includes a large sample size facilitating the investigation of postinjection pain
      reduction overall and by specific articulation. MATERIALS AND METHODS: Three
      hundred forty-eight patients with imaging-guided diagnostic or therapeutic
      injections into the foot articulations, with complete preinjection and 20- to 30
      minute postinjection numeric rating scale pain data were included. The
      proportions of patients reporting clinically relevant pain reduction (>= 50%)
      were calculated overall and for specific subgroups. The risk ratio comparing
      patients with osteoarthritis to those without osteoarthritis was calculated.
      Analysis of variance was used to compare outcomes between subgroups of patients
      based on injection site. The unpaired Student t test was used to compare
      responses of men versus women, those with and without a diagnosis of
      osteoarthritis, and more experienced versus less experienced radiologists.
      RESULTS: Sixty-four percent of patients (224/348) reported clinically relevant
      pain reduction. The average decrease overall was 56% (SD, 36). Injections into
      the Lisfranc articulation were significantly more effective (61% pain reduction,
      p = 0.007) compared with other sites, with 74% of patients obtaining clinically
      relevant pain relief. Patients with osteoarthritis reported more relief (62%)
      compared with those without (50%, p = 0.002). No difference in outcomes comparing
      musculoskeletal radiologists with residents or fellows in training was found.
      CONCLUSION: Nearly two thirds of patients receiving imaging-guided injections
      into the foot articulations reported clinically relevant pain reduction. Lisfranc
      joint injections and patients with a diagnosis of osteoarthritis responded
      better.

PMID- 21940585
TI  - Bisphosphonate-related complete atypical subtrochanteric femoral fractures:
      diagnostic utility of radiography.
AB  - OBJECTIVE: The objective of our study was to evaluate the diagnostic utility of
      conventional radiography for diagnosing bisphosphonate-related atypical
      subtrochanteric femoral fractures. MATERIALS AND METHODS: Retrospective
      interpretation of 38 radiographs of complete subtrochanteric and diaphyseal
      femoral fractures in two patient groups-one group being treated with
      bisphosphonates (19 fractures in 17 patients) and a second group not being
      treated with bisphosphonates (19 fractures in 19 patients)-was performed by three
      radiologists. The readers assessed four imaging criteria: focal lateral cortical
      thickening, transverse fracture, medial femoral spike, and fracture comminution.
      The odds ratios and the sensitivity, specificity, and accuracy of each imaging
      criterion as a predictor of bisphosphonate-related fractures were calculated.
      Similarly, the interobserver agreement and the sensitivity, specificity, and
      accuracy of diagnosing bisphosphonate-related fractures (i.e., atypical femoral
      fractures) were determined for the three readers. RESULTS: Among the candidate
      predictors of bisphosphonate-related fractures, focal lateral cortical thickening
      and transverse fracture had the highest odds ratios (76.4 and 10.1,
      respectively). Medial spike and comminution had odd ratios of 3.8 and 0.63,
      respectively. Focal lateral cortical thickening and transverse fracture were also
      the most accurate factors for detecting bisphosphonate-related fractures for all
      readers. The sensitivity, specificity, and overall accuracy for diagnosing
      bisphosphonate-related fractures were 94.7%, 100%, and 97.4% for reader 1; 94.7%,
      68.4%, and 81.6% for reader 2; and 89.5%, 89.5%, and 89.5% for reader 3,
      respectively. The interobserver agreement was substantial (kappa > 0.61).
      CONCLUSION: Radiographs are reliable for distinguishing between complete femoral
      fractures related to bisphosphonate use and those not related to bisphosphonate
      use. Focal lateral cortical thickening and transverse fracture are the most
      dependable signs, showing high odds ratios and the highest accuracy for
      diagnosing these fractures.

PMID- 21940586
TI  - Alterations of the transverse ligament: an MRI study comparing patients with
      acute whiplash and matched control subjects.
AB  - OBJECTIVE: The objective of our study was to evaluate whether there is injury to
      the transverse ligament of the atlas in patients with acute whiplash. MATERIALS
      AND METHODS: Ninety patients with an acute (< 48 hours) symptomatic whiplash
      associated injury and 90 healthy age- and sex-matched asymptomatic control
      subjects (mean age of patients and control subjects, 36 years) were included. The
      maximal sagittal thickness of the transverse ligament was measured on midsagittal
      T1 volumetric interpolated breath-hold examination (VIBE) images and transverse
      reformatted VIBE images. The signal intensity of the transverse ligament was
      measured on transverse STIR images and on transverse reformatted T1 VIBE images
      before and after IV administration of gadoterate. Contrast between the transverse
      ligament and CSF and alterations of contrast after gadoterate injection were
      calculated. RESULTS: Patients had a minimally thicker transverse ligament
      (posttraumatic swelling) than control subjects, and the difference in thickness
      was significant in men only (p = 0.03). In patients, a significant signal
      alteration of the transverse ligament (p = 0.03) was seen on STIR (posttraumatic
      edema) and native VIBE sequences. The contrast between the transverse ligament
      and the CSF on VIBE images was significantly (p = 0.005) lower in patients than
      in control subjects. With the application of a contrast agent, the contrast
      difference between the transverse ligament and CSF in patients and control
      subjects was less pronounced (p = 0.038). There was no abnormal uptake of
      contrast agent by the transverse ligament or CSF. CONCLUSION: The results of our
      study indicate possible involvement of the transverse ligament in whiplash
      injury. Although MRI may be helpful to study injury-related changes of anatomic
      structures in cohorts, it is not suited for individual diagnosis because the
      alterations are too small.

PMID- 21940587
TI  - MRI versus radiography of acromioclavicular joint dislocation.
AB  - OBJECTIVE: Acromioclavicular joint injuries are usually diagnosed by clinical and
      radiographic assessment with the Rockwood classification, which is crucial for
      treatment planning. In view of the implementation of MRI for visualization of the
      acromioclavicular joint, the purpose of this study was to describe the MRI
      findings of acromioclavicular joint dislocation in comparison with the
      radiographic findings. SUBJECTS AND METHODS: Forty-four patients with suspected
      unilateral acromioclavicular joint dislocation after acute trauma were enrolled
      in this prospective study. All patients underwent digital radiography and 1-T MRI
      with a surface phased-array coil. MRI included coronal proton density-weighted
      turbo spin-echo and coronal 3D T1-weighted fast field-echo water-selective
      sequences. The Rockwood classification was used to assess acromioclavicular joint
      injuries at radiography and MRI. An adapted Rockwood classification was used for
      MRI evaluation of the acromioclavicular joint ligaments. The classifications of
      acromioclavicular joint dislocations diagnosed with radiography and MRI were
      compared. RESULTS: Among 44 patients with Rockwood type I-IV injuries on
      radiographs, classification on radiographs and MR images was concordant in 23
      (52.2%) patients. At MRI, the injury was reclassified to a less severe type in 16
      (36.4%) patients and to a more severe type in five (11.4%) patients. Compared
      with the findings according to the original Rockwood system, with the adapted
      system that included MRI findings, additional ligamentous lesions were found in
      11 (25%) patients. CONCLUSION: In a considerable number of patients, the MRI
      findings change the Rockwood type determined with radiography. In addition to
      clinical assessment and radiography, MRI may yield important findings on
      ligaments that may influence management.

PMID- 21940588
TI  - Use of 18F-FDG PET/CT as a predictive biomarker of outcome in patients with head
      and-neck non-squamous cell carcinoma.
AB  - OBJECTIVE: The purpose of this article is to establish whether pretreatment (18)F
      FDG uptake predicts disease-free survival (DFS) and overall survival in patients
      with head-and-neck non-squamous cell carcinoma (SCC). MATERIALS AND METHODS:
      Eighteen patients (six women and 12 men; mean [+/- SD] age at diagnosis, 57.89 +/
      13.54 years) with head-and-neck non-SCC were included. Tumor FDG uptake was
      measured by the maximum standardized uptake value (SUV(max)) and was corrected
      for background liver FDG uptake to derive the corrected SUV(max). Receiver
      operating characteristic analyses were used to predict the optimal corrected
      SUV(max) cutoffs for respective outcomes of DFS (i.e., absence of recurrence) and
      death. RESULTS: The mean corrected SUV(max) of the 18 head-and-neck tumors was
      5.63 +/- 3.94 (range, 1.14-14.29). The optimal corrected SUV(max) cutoff for
      predicting DFS and overall survival was 5.79. DFS and overall survival were
      significantly higher among patients with corrected SUV(max) < 6 than among
      patients with corrected SUV(max) >= 6. The mean DFS for patients with corrected
      SUV(max) < 6 was 25.7 +/- 11.14 months, and the mean DFS for patients with
      corrected SUV(max) >= 6 was 7.88 +/- 7.1 months (p < 0.018). Among patients with
      corrected SUV(max) < 6, none died, and the mean length of follow-up for this
      group was 35.2 +/- 9.96 months. All of the patients who died had corrected
      SUV(max) >= 6, and the overall survival for this group was 13.28 +/- 12.89 months
      (p < 0.001). CONCLUSION: FDG uptake, as measured by corrected SUV(max), may be a
      predictive imaging biomarker for DFS and overall survival in patients with head
      and-neck non-SCC.

PMID- 21940589
TI  - Comparative analysis of ferumoxytol and gadoteridol enhancement using T1- and T2
      weighted MRI in neuroimaging.
AB  - OBJECTIVE: Ferumoxytol, an ultrasmall superparamagnetic iron oxide particle, has
      been suggested as a potential alternative MRI contrast agent in patients with
      renal failure. We compared ferumoxytol to gadoteridol enhancement on T1- and T2
      weighted MRI in CNS disorders to explore its diagnostic utility. SUBJECTS AND
      METHODS: Data were collected from three protocols in 70 adults who underwent
      alternate-day gadoteridol- and ferumoxytol-enhanced MRI using identical
      parameters. Two neuroradiologists measured lesion-enhancing size and intensity on
      contrast-enhanced T1-weighted images in consensus. T2-weighted images were
      evaluated for the presence of contrast-enhanced hypointensity. Mixed model
      repeated measures analysis of variance determined differences between T1-weighted
      enhancement size and intensity for individual protocols and group. RESULTS: After
      exclusions, 49 MRI studies in 29 men and 20 women (mean age, 51 years) were
      assessed. T1-weighted estimated enhancing sizes were different between agents (p
      = 0.0456) as a group; however, no differences were observed with untreated
      gliomas (n = 17) in two protocols (p = 1.0 and p = 0.99, respectively).
      Differences in T1-weighted enhancement intensity between agents were significant
      for the group overall (p = 0.0006); however, three-way interactions were not
      significant (p = 0.1233). T2-weighted images were assessed for contrast-enhanced
      hypointensity, observed in 26 of 49 (53%) ferumoxytol and zero of 49 (0%)
      gadoteridol scans. CONCLUSION: Ferumoxytol may be a useful MRI contrast agent in
      patients who are unable to receive gadolinium-based contrast agents. Greater
      experience with a wider variety of disorders is necessary to understand
      differences in enhancement with ferumoxytol compared with gadolinium-based
      contrast agents, given their different mechanisms of action.

PMID- 21940590
TI  - Next generation radiologic-pathologic correlation in oncology: Rad-Path 2.0.
AB  - OBJECTIVE: The bedrock of radiology has been radiologic-pathologic (Rad-Path)
      correlation: the correlation of imaging to ex vivo gross and histopathologic
      findings of disease. This classical view is being challenged by our increasing
      understanding of the molecular basis of disease, particularly in oncology. The
      traditional lines in diagnostic sciences have blurred with the development of new
      in vitro diagnostic molecular assays and molecular imaging methods as well as the
      growing evidence that conventional diagnostic imaging has potential use in
      understanding genomic properties of disease. The purpose of this article is to
      make the case for a fundamental shift to the next generation of Rad-Path
      correlation (Rad-Path 2.0). CONCLUSION: The future success of radiology will
      require not only continued technologic advances in physical and life sciences but
      also the convergence of previously distinct diagnostic disciplines.

PMID- 21940591
TI  - Focal Periphyseal Edema (FOPE) zone on MRI of the adolescent knee: a potentially
      painful manifestation of physiologic physeal fusion?
AB  - OBJECTIVE: We have termed an MRI finding in the knees of adolescents
      characterized by a focal bone marrow edema pattern centered about the closing
      physis a "FOPE"-that is, focal periphyseal edema-zone. The cause of this
      appearance is unknown. Therefore, the purpose of this article is to review the
      MRI appearance of the FOPE zone and to postulate a causative mechanism. MATERIALS
      AND METHODS: FOPE zones were identified on knee MRI examinations performed for
      pain in 12 patients (seven girls, five boys; age range, 11 years 9 months-15
      years 8 months); the examinations were collected over 5 years. Clinical history,
      skeletal maturity, size and location of FOPE zone, and concomitant ipsilateral
      knee abnormalities were recorded at presentation and on follow-up MRI
      examinations when available. Bone ages were estimated from knee radiographs using
      published standards. RESULTS: Fifteen FOPE zones measuring 2-27 mm were
      identified: eight were femoral; six, tibial; and one, fibular. All were centrally
      located. All physes were patent, albeit narrowed. The radiographic appearance of
      the physes was similar for both sexes. All patients with estimated bone ages of
      11 and 12 years were girls. Two other girls had bone ages closer to 14 years,
      whereas all boys had estimated bone ages of 13 or 14 years. CONCLUSION: On knee
      MRI, a FOPE zone can be seen in adolescents and likely relates to the early
      stages of physiologic physeal closure. It may be associated with pain
      particularly when no other MRI abnormalities are present. When the characteristic
      appearance of a FOPE zone is observed on MRI, we suggest that it not be mistaken
      for an abnormality, requires no invasive diagnostic procedure, and does not need
      imaging follow-up.

PMID- 21940592
TI  - Prevalence of the classic metaphyseal lesion in infants at low versus high risk
      for abuse.
AB  - OBJECTIVE: The purpose of this article is to determine the relative likelihood of
      encountering a classic metaphyseal lesion in infants at low and high risk for
      abuse. MATERIALS AND METHODS: This 10-year retrospective study compared the
      prevalence of the classic metaphyseal lesion on high-detail American College of
      Radiology-standardized skeletal surveys in infants at low and high risk for
      abuse. Low-risk infants met all of the following criteria: skull fracture without
      significant intracranial injury on CT, history of a fall, and no other social
      risk factors for abuse. High-risk infants met all of the following criteria:
      significant intracranial injury, retinal hemorrhages, and skeletal injuries
      (excluding classic metaphyseal lesions and skull fractures). Differences between
      the two groups were calculated using the Fisher exact test. RESULTS: There were
      42 low-risk infants (age range, 0.4-12 months; mean age, 4.4 months) and 18 high
      risk infants (age range, 0.8-10.3 months; mean age, 4.6 months). At least one
      classic metaphyseal lesion was identified in nine infants (50%) in the high-risk
      category. No classic metaphyseal lesions were identified in the low-risk group.
      The relative prevalence of classic metaphyseal lesions in the low-risk group
      (0/42) versus that in the high-risk group (9/18) was statistically significant (p
      < 0.0001; 95% CI, 0-8% to 29-76%). CONCLUSION: Classic metaphyseal lesions are
      commonly encountered in infants at high risk for abuse and are rare in infants
      with skull fractures associated with falls, but no other risk factors. The
      findings support the view that the classic metaphyseal lesion is a high
      specificity indicator of infant abuse.

PMID- 21940593
TI  - Atypical ductal hyperplasia diagnosed at 11-gauge vacuum-assisted breast biopsy
      performed on suspicious clustered microcalcifications: could patients without
      residual microcalcifications be managed conservatively?
AB  - OBJECTIVE: The purpose of our study was to establish whether it might be safe for
      women with a diagnosis of atypical ductal hyperplasia (ADH) at stereotactically
      guided vacuum-assisted breast biopsy without any residual microcalcification
      after the procedure to undergo mammographic follow-up instead of surgical biopsy.
      MATERIALS AND METHODS: From October 2003 to January 2009, 1173 consecutive 11
      gauge vacuum-assisted breast biopsy procedures were performed. ADH was found in
      the specimens of 114 patients who underwent vacuum-assisted breast biopsy for a
      single cluster of suspicious microcalcifications smaller than 15 mm; 49 had
      residual microcalcifications, and 65 had microcalcifications completely removed
      by the procedure. Of 49 patients with residual microcalcifications, 41 underwent
      surgical biopsy. Of 65 patients without residual microcalcifications, 26
      underwent surgical biopsy, 35 were not surgically treated and were managed
      conservatively with mammographic follow-up, and 4 had follow-up of less than 24
      months. RESULTS: In 41 patients with residual microcalcifications who underwent
      surgical biopsy, 8 malignant lesions were found at surgery. The underestimation
      rate was 20% (8/41). In 26 patients without residual microcalcifications who
      underwent surgical biopsy, no malignant lesions were found. One malignant lesion
      was found in the 35 patients managed conservatively at follow-up. The
      underestimation rate in patients without residual microcalcifications using
      surgical biopsy or mammographic follow-up as the reference standard was 1.6%
      (1/61). CONCLUSION: Patients without residual microcalcifications after vacuum
      assisted breast biopsy could possibly be managed in a conservative way with
      mammographic follow-up.

PMID- 21940594
TI  - Cortical desmoid: a misnomer?

PMID- 21940595
TI  - Micronized ferric pyrophosphate supplied through extruded rice kernels improves
      body iron stores in children: a double-blind, randomized, placebo-controlled
      midday meal feeding trial in Indian schoolchildren.
AB  - BACKGROUND: Micronized ferric pyrophosphate (MFPP) in extruded rice kernels mixed
      in a rice-based meal could be an effective strategy for improving iron status of
      children in India. OBJECTIVE: The objective was to determine the impact of MFPP
      supplied through extruded rice kernels in a rice-based meal on iron status of
      children participating in the midday meal (MDM) scheme in India. DESIGN: The
      sensory characteristics of cooked rice containing MFPP in extruded rice kernels,
      in vitro availability, and loss of iron during cooking from a typical MDM
      consisting of 125 g rice (dry weight) containing 19 mg Fe [fortified rice (FR);
      normal rice mixed with Ultra Rice (extruded kernels containing MFPP of ~3.14-MUm
      mean particle size)] in comparison with unfortified rice (UFR) were tested. A
      double-blind, 8-mo, placebo-controlled trial was conducted in 5-11-y-old
      schoolchildren (n = 140) who were randomly assigned to receive either an FR-MDM
      or a UFR-MDM. Average consumption amounts of the MDM, height, weight, hemoglobin,
      ferritin, and C-reactive protein were measured at baseline and at 8 mo. RESULTS:
      The sensory qualities of cooked FR and UFR were similar. The in vitro iron
      availability from FR-MDM (1.3%) was significantly (P < 0.05) lower than that from
      UFR-MDM (3.3%). Providing FR-MDM to the schoolchildren for 8 mo improved ferritin
      significantly (P < 0.001), by 8.2 +/- 2.10 MUg/L. However, the increase in
      hemoglobin was similar between groups (FR: 0.99 +/- 0.10 g/dL; UFR: 1.15 +/- 0.10
      g/dL), which suggests that other factors beyond additional iron intake had a
      large influence on hemoglobin concentration. The prevalence of iron deficiency
      decreased significantly (P < 0.05) in the FR group (33-14%) and increased
      marginally in the UFR group (31-37%). The prevalence of anemia and iron
      deficiency anemia was similar between groups at baseline and at 8 mo. CONCLUSION:
      Regular intake of 19 mg Fe/d in MFPP supplied through extruded rice kernels
      improves iron stores and reduces iron deficiency among schoolchildren in India.

PMID- 21940596
TI  - Diet and bone mineral density study in postmenopausal women from the TwinsUK
      registry shows a negative association with a traditional English dietary pattern
      and a positive association with wine.
AB  - BACKGROUND: The effect of diet on bone mineral density (BMD) remains
      controversial, mainly because of difficulties in isolating dietary factors from
      the confounding influences of age, lifestyle, and genetic factors. OBJECTIVE: The
      aim of this study was to use a novel method to examine the relation between BMD
      and diet. DESIGN: A co-twin control study design with linear regression modeling
      was used to test for associations between BMD and habitual intakes of calcium,
      vitamin D, protein, and alcohol plus 5 previously identified dietary patterns in
      postmenopausal women from the TwinsUK registry. This approach exploited the
      unique matching of twins to provide an estimate of an association that was not
      confounded by age, genetic background, or shared lifestyle. RESULTS: In >2000
      postmenopausal women (BMD data on 1019, 1218, and 1232 twin pairs at the hip
      neck, hip, and spine, respectively), we observed a positive association between
      alcohol intake (from wine but not from beer or spirits) and spine BMD (P = 0.01)
      and a negative association with a traditional 20th-century English diet at the
      hip neck (P = 0.01). Both associations remained borderline significant after
      adjustment for mean twin-pair intakes (P = 0.04 and P = 0.055, respectively).
      Other dietary patterns and intakes of calcium, vitamin D, and protein were
      unrelated to BMD. CONCLUSION: Our results showed that diet has an independent but
      subtle effect on BMD; wine intake was positively associated with spine BMD,
      whereas a traditional (20th-century) English diet had a negative association with
      hip BMD.

PMID- 21940597
TI  - Butyrate esterified to starch is released in the human gastrointestinal tract.
AB  - BACKGROUND: Short-chain fatty acids (SCFAs) maintain human colonic function and
      may help prevent colonic disease. A study with ileostomists showed that starches
      acylated with specific SCFAs largely survive passage through the small intestine,
      but the percentage released in the colon has not been established. OBJECTIVE: The
      objective was to determine the percentage of ingested esterified butyrate
      released in the human gastrointestinal tract. DESIGN: The study was a randomized,
      crossover, controlled trial consisting of baseline and four 2-wk periods during
      which 16 volunteers consumed diets low in resistant starch plus 20 and 40 g
      cooked high-amylose maize starch (HAMS: HAMS20 or HAMS40) or butyrylated HAMS
      (HAMSB20 or HAMSB40) daily. HAMSB20 contained 31.8 mmol esterified butyrate.
      Complete 48-h fecal collections were made on days 2-3 and 12-13 of each period.
      RESULTS: Free fecal butyrate concentrations were higher after HAMSB40 than after
      HAMSB20 (P < 0.005) and HAMS (P < 0.0001) and higher than baseline data (P <
      0.0001). Fecal esterified butyrate concentrations were highest in the HAMSB40
      (days 12-13; P < 0.0001) group, and concentrations in the HAMSB40 (days 2-3) and
      HAMSB20 groups were higher than those in the HAMS groups and those at baseline (P
      < 0.0001). Ingestion of HAMSB20 and HAMSB40 resulted in the release of 26.8 +/-
      1.0 and 50.2 +/- 2.4 mmol butyrate/d (days 12-13) (84.2 +/- 3.0% and 79.0 +/-
      3.1% of total ingested esterified butyrate), respectively, in the
      gastrointestinal tract. By calculation, ~57.2% of ingested esterified butyrate
      was released in the colon. Microbial analysis showed that this release was
      probably facilitated mainly by Parabacteroides distasonis, which increased in
      abundance with HAMSB40 (days 12-13) (P < 0.001). CONCLUSIONS: This study shows
      that cooked butyrylated starch delivers esterified butyrate to the human colon
      effectively and has the potential to improve human bowel health. This trial is
      registered in the Australian Clinical Trials Registry as ACTRN012606000398505.

PMID- 21940598
TI  - Effects of a 2-y dietary weight-loss intervention on cholesterol metabolism in
      moderately obese men.
AB  - BACKGROUND: Long-term dietary weight loss results in complex metabolic changes.
      However, its effect on cholesterol metabolism in obese subjects is still unclear.
      OBJECTIVE: We assessed the effects of 2 y of weight loss achieved with various
      diet regimens on phytosterols (markers of intestinal cholesterol absorption),
      lanosterol (marker of de novo cholesterol synthesis), and changes in
      apolipoprotein concentrations. DESIGN: We conducted the 2-y Dietary Intervention
      Randomized Controlled Trial (DIRECT-a study of low-fat, Mediterranean, and low
      carbohydrate diets). We assessed circulating phytosterol and lanosterol
      concentrations and their ratios to cholesterol and apolipoproteins A-I and B-100
      in 90 DIRECT participants at 0, 6, and 24 mo. RESULTS: We observed a significant
      upregulation of the markers of cholesterol absorption (campesterol: +16.8%, P <
      0.001) and a downregulation of the markers of cholesterol synthesis (lanosterol: 
      16.5%, P = 0.008) during the active weight-loss phase (first 6 mo, weight loss of
      5%, 6%, and 10% in the 3 diet groups, respectively), followed by a rebound
      (campesterol: -6.2%, P = 0.045; lanosterol: +43.7%, P < 0.001) during the next 18
      mo (weight gain of 1%, 1%, and 2% in the 3 diet groups, respectively). HDL
      cholesterol continuously increased during the study (17.0%, P < 0.001), whereas
      LDL cholesterol remained constant. At the end of the 24-mo follow-up period,
      campesterol (P < 0.001) and lanosterol (P = 0.016) amounts were significantly
      higher than baseline values. The concentration of apolipoprotein B-100 correlated
      with cholesterol metabolism (rho = 0.299 and P = 0.020 for lanosterol; rho = 
      0.105 and NS for campesterol), and the homeostasis model assessment of insulin
      resistance correlated with lanosterol (rho = 0.09, P = 0.001). CONCLUSIONS: Long
      term weight loss is related to a characteristic response suggestive of altered
      cholesterol and apolipoprotein metabolism. Various diets have a similar effect on
      these effects. DIRECT is registered at clinicaltrials.gov as NCT00160108.

PMID- 21940599
TI  - Plasma sterol evidence for decreased absorption and increased synthesis of
      cholesterol in insulin resistance and obesity.
AB  - BACKGROUND: The rise in LDL with egg feeding in lean insulin-sensitive (LIS)
      participants is 2- and 3-fold greater than in lean insulin-resistant (LIR) and
      obese insulin-resistant (OIR) participants, respectively. OBJECTIVE: We
      determined whether differences in cholesterol absorption, synthesis, or both
      could be responsible for these differences by measuring plasma sterols as indexes
      of cholesterol absorption and endogenous synthesis. DESIGN: Plasma sterols were
      measured by gas chromatography-mass spectrometry in a random subset of 34 LIS, 37
      LIR, and 37 OIR participants defined by the insulin sensitivity index (S(I)) and
      by BMI criteria selected from a parent group of 197 participants. Cholestanol and
      plant sterols provide a measure of cholesterol absorption, and lathosterol
      provides a measure of cholesterol synthesis. RESULTS: The mean (+/-SD) ratio of
      plasma total absorption biomarker sterols to cholesterol was 4.48 +/- 1.74 in
      LIS, 3.25 +/- 1.06 in LIR, and 2.82 +/- 1.08 in OIR participants. After
      adjustment for age and sex, the relations of the absorption sterol-cholesterol
      ratios were as follows: LIS > OIR (P < 0.001), LIS > LIR (P < 0.001), and LIR >
      OIR (P = 0.11). Lathosterol-cholesterol ratios were 0.71 +/- 0.32 in the LIS
      participants, 0.95 +/- 0.47 in the LIR participants, and 1.29 +/- 0.55 in the OIR
      participants. After adjustment for age and sex, the relations of lathosterol
      cholesterol ratios were as follows: LIS < OIR (P < 0.001), LIS < LIR (P = 0.03),
      and LIR < OIR (P = 0.002). Total sterol concentrations were positively associated
      with S(I) and negatively associated with obesity, whereas lathosterol
      correlations were the opposite. CONCLUSIONS: Cholesterol absorption was highest
      in the LIS participants, whereas cholesterol synthesis was highest in the LIR and
      OIR participants. Therapeutic diets for hyperlipidemia should emphasize low
      cholesterol diets in LIS persons and weight loss to improve S(I) and to decrease
      cholesterol overproduction in LIR and OIR persons.

PMID- 21940600
TI  - n-3 PUFAs in cancer, surgery, and critical care: a systematic review on clinical
      effects, incorporation, and washout of oral or enteral compared with parenteral
      supplementation.
AB  - BACKGROUND: n-3 (omega-3) Fatty acids (FAs) may have beneficial effects in
      patients with cancer or in patients who undergo surgery or critical care.
      OBJECTIVE: Our aim was to systematically review the effects of oral or enteral
      and parenteral n-3 FA supplementation on clinical outcomes and to describe the
      incorporation of n-3 FAs into phospholipids of plasma, blood cells, and mucosal
      tissue and the subsequent washout in these patients. DESIGN: We investigated the
      supplementation of n-3 FAs in these patients by using a systematic literature
      review. RESULTS: In cancer, the oral or enteral supplementation of n-3 FAs
      contributed to the maintenance of body weight and quality of life but not to
      survival. We did not find any studies on parenteral supplementation of n-3 FAs in
      cancer. In surgical oncology, we did not find any studies on enteral
      supplementation of n-3 FAs. However, postoperative parenteral supplementation in
      surgical oncology may reduce the length of a hospital stay. For general surgery,
      we did not find any studies on enteral supplementation of n-3 FAs, and evidence
      on parenteral supplementation was insufficient. In critical care, enteral
      supplementation of n-3 FAs had beneficial effects on clinical outcomes; evidence
      on parenteral supplementation in critical care was inconsistent. The
      incorporation of n-3 FAs in plasma and blood cells was slower with enteral
      supplementation (4-7 d) than with parenteral supplementation (1-3 d). The washout
      was 5-7 d. CONCLUSIONS: This review shows the beneficial effects of n-3 FA
      supplementation in cancer, surgical oncology, and critical care patients.
      Supplementation in these specific patient populations could be considered with
      the route of administration taken into account.

PMID- 21940601
TI  - Interpreting and applying CYP450 genomic test results to psychotropic
      medications.
AB  - The promises of personalized medicine have health care professionals and the
      public at large in great anticipation of the idea that understanding a patient's
      genetic composition will provide clear answers to their treatment needs. For many
      practitioners in mental health care, there has been a question about whether or
      not CYP450 genetic polymorphisms can reliably inform psychotropic treatment
      response and tolerability. Unfortunately, the published evidence addressing this
      issue is mixed with only some researchers finding a positive correlation between
      a patient's inherited metabolizer status and either response or tolerability to a
      specific medication or a therapeutic class of medications. Despite this mixed
      evidence, clinical practitioners have started genotyping CYP450 enzymes for some
      of their patients with the hope that these data may shed some light on difficult
      treatment decisions. This review will focus on the metabolism of psychotropics
      and important aspects of understanding the genomics of the cytochrome P450
      enzymes 2C9, 2C19, and 2D6. Additionally this review will illustrate sample
      laboratory reports from 4 different laboratories which test for CYP450 genomics
      and then finally provide 3 different case scenarios which illustrate a process
      that pharmacists can use when applying genomic laboratory data to patient care.

PMID- 21940602
TI  - The use of omega-3 fatty acids in mental illness.
AB  - PURPOSE: This article will summarize the current evidence on the effects of omega
      3 fatty acids on prevention and treatment of mental illness. BACKGROUND: Omega-3
      fatty acids are involved in many physiologic processes. Since they cannot be made
      de novo in the body, they are considered essential nutrients. As the Western diet
      evolved, dietary intake of fatty acids has shifted to increased omega-6 fatty
      acids and decreased omega-3 fatty acids intake. These changes have been
      correlated with numerous differences in prevalence and course of mental
      illnesses. METHODS: A MEDLINE search from 1966 to December 2010 was completed to
      identify studies comparing changes in symptoms, functioning, other outcomes,
      and/or side effects in patients treated with omega-3 fatty acids for mental
      illness. The studies were reviewed and reported by specific psychiatric disorder
      studied. CONCLUSIONS: Omega-3 fatty acids play a role in many biologic functions.
      Epidemiologic data implicate omega-3 fatty acid deficiencies in many mental
      illnesses. Data are most robust for omega-3 fatty acids' role in affective
      disorders. However, data are conflicting, negative, or absent for most mental
      illnesses.

PMID- 21940603
TI  - Toward new avenues in the treatment of nonsuicidal self-injury.
AB  - The treatment of self-injury, or self-destruction of one's own body tissue, has
      become a new focus for both researchers and clinicians. Traditionally, the field
      of self-injury has distinguished between the behaviors exhibited among
      individuals with a developmental disability (self-injurious behaviors [SIBs]) and
      those present within a normative population (nonsuicidal self-injury [NSSI]).
      Despite this distinction, many pharmacotherapies for self-injury have been
      administered for both populations. The current review begins by summarizing the
      available efficacy studies investigating common pharmacological interventions in
      the treatment of self-injury. These studies are organized based on the most
      empirically supported neurochemical pathways in the development or maintenance of
      NSSI: endogenous opiods and monoamines. Although significant advances have been
      made in the field, conclusions based on efficacy studies of the pharmacological
      interventions used in the treatment of self-injury have been somewhat
      inconsistent. Finally, the review includes a discussion about potential avenues
      in the pharmacological treatment of NSSI via animal models of self-injury. Animal
      models present a unique opportunity to test neurobiological theories of self
      injury using a controlled, systematic approach. Clinical considerations are
      presented as they relate to the available research findings and best practices in
      the treatment of self-injury.

PMID- 21940604
TI  - Side effects of the therapy with peginterferon and ribavirin in chronic hepatitis
      C: a small audit.
AB  - This study sought to decribe, quantify, and classify any adverse reactions
      occurring in patients with chronic hepatitis C treated with peginterferon and
      ribavirin, as well as verify the occurrence of potential medication interactions.
      The most prevalent reactions were fatigue (84.8%), fever (83%), weight loss
      (80%), irritability (74%), and body pain (72%). Most of the reactions were
      classified as mild (95%), whereas 4.5% were classified as moderate and 0.4% as
      severe. Adverse reactions led to the rearrangement of therapy for 9 patients
      (20%), where there was a reduction in dose for 7 (15%), temporary interruption of
      treatment for 5 (11%), and permanent discontinuation for 3 patients (7%). A total
      of 11 potential medication interactions were identified in 9 patients (20%), with
      the most frequent between peginterferon-alpha2a and captopril (45%). Given the
      above, it is observed that the treatment of chronic hepatitis C is marked by
      several adverse reactions of varying severity, which can interfere with the
      patient's quality of life or in treatment compliance, and that can be aggravated
      by potential drug-drug interactions.

PMID- 21940606
TI  - Physiological interactions between Na(v)1.7 and Na(v)1.8 sodium channels: a
      computer simulation study.
AB  - We have examined the question of how the level of expression of sodium channel
      Na(v)1.8 affects the function of dorsal root ganglion (DRG) neurons that also
      express Na(v)1.7 channels and, conversely, how the level of expression of sodium
      channel Na(v)1.7 affects the function of DRG neurons that also express Na(v)1.8,
      using computer simulations. Our results demonstrate several previously
      undescribed effects of expression of Na(v)1.7: 1) at potentials more negative
      than -50 mV, increasing Na(v)1.7 expression reduces current threshold. 2)
      Na(v)1.7 reduces, but does not eliminate, the dependence of action potential (AP)
      threshold on membrane potential. 3) In cells that express Na(v)1.8, the presence
      of Na(v)1.7 results in larger amplitude subthreshold oscillations and increases
      the frequency of repetitive firing. Our results also demonstrate multiple effects
      of expression of Na(v)1.8: 1) dependence of current threshold on membrane
      potential is eliminated or reversed by expression of Na(v)1.8 at >=50% of normal
      values. 2) Expression of Na(v)1.8 alone, in the absence of Na(v)1.7, can support
      subthreshold oscillation. 3) Na(v)1.8 is required for generation of overshooting
      APs, and its expression results in a prolonged AP with an inflection of the
      falling phase. 4) Increasing levels of expression of Na(v)1.8 result in a
      reduction in the voltage threshold for AP generation. 5) Increasing levels of
      expression of Na(v)1.8 result in an attenuation of Na(v)1.7 current during
      activity evoked by sustained depolarization due, at least in part, to
      accumulation of fast inactivation by Na(v)1.7 following the first AP. These
      results indicate that changes in the level of expression of Na(v)1.7 and Na(v)1.8
      may provide a regulatory mechanism that tunes the excitability of small DRG
      neurons.

PMID- 21940605
TI  - Feature integration in visual working memory: parietal gamma activity is related
      to cognitive coordination.
AB  - The mechanism by which distinct subprocesses in the brain are coordinated is a
      central conundrum of systems neuroscience. The parietal lobe is thought to play a
      key role in visual feature integration, and oscillatory activity in the gamma
      frequency range has been associated with perception of coherent objects and other
      tasks requiring neural coordination. Here, we examined the neural correlates of
      integrating mental representations in working memory and hypothesized that
      parietal gamma activity would be related to the success of cognitive
      coordination. Working memory is a classic example of a cognitive operation that
      requires the coordinated processing of different types of information and the
      contribution of multiple cognitive domains. Using magnetoencephalography (MEG),
      we report parietal activity in the high gamma (80-100 Hz) range during
      manipulation of visual and spatial information (colors and angles) in working
      memory. This parietal gamma activity was significantly higher during manipulation
      of visual-spatial conjunctions compared with single features. Furthermore, gamma
      activity correlated with successful performance during the conjunction task but
      not during the component tasks. Cortical gamma activity in parietal cortex may
      therefore play a role in cognitive coordination.

PMID- 21940607
TI  - Analyses of the facilitatory effect of orexin on eating and masticatory muscle
      activity in rats.
AB  - The orexins (orexin-A and orexin-B) are neuropeptides that are secreted from
      neurons in the lateral hypothalamus and that participate in the regulation of
      feeding behavior. It remains to be determined, however, how the orexins exert
      their effects on feeding behavior, including masticatory movements. To this end,
      we analyzed food intake behavior and masticatory muscle activity using video
      analysis and electromyography (EMG) recording methods. The results showed that
      the cumulative food intake over 4 h was larger in rats intraventricularly
      injected with either orexin-A or orexin-B than in saline-injected control rats.
      The latency to eating and the feeding time for a fixed amount of pellets were
      shortened by injections of orexins in a dose-dependent manner, with a more potent
      effect by orexin-A than orexin-B. The shorter feeding time corresponded to a
      decreased number of chewing cycles. EMG recordings from both the digastric and
      masseter muscles showed two distinct patterns of bursts corresponding to the
      gnawing and chewing phases. After the injection of orexin-A, the magnitude of the
      bursts became larger in both phases in the masseter muscle, the burst duration
      became longer in the chewing phase in the masseter muscle, and the interburst
      interval became shortened in the gnawing phase in both muscles. Consequently, the
      burst frequency in the chewing phase was increased in the digastric muscle and,
      conversely, reduced in the masseter muscle. These results suggest that the orexin
      A-induced facilitatory feeding behavior is characterized by a dynamic jaw-opener
      activity that opens the mouth rapidly and a powerful jaw-closer activity for
      crushing the increased amount of food taken into the mouth. The possible
      involvement of orexin-A in binge eating disorder is discussed.

PMID- 21940608
TI  - Multiple sites of extinction for a single learned response.
AB  - Most learned responses can be diminished by extinction, a process that can be
      engaged when a conditioned stimulus (CS) is presented but not reinforced. We
      present evidence that plasticity in at least two brain regions can mediate
      extinction of responses produced by trace eyelid conditioning, where the CS and
      the reinforcing stimulus are separated by a stimulus-free interval. We observed
      individual differences in the effects of blocking extinction mechanisms in the
      cerebellum, the structure that, along with several forebrain structures, mediates
      acquisition of trace eyelid responses; in some rabbits extinction was prevented,
      whereas in others it was largely unaffected. We also show that cerebellar
      mechanisms can mediate extinction when noncerebellar mechanisms are bypassed.
      Together, these observations indicate that trace eyelid responses can be
      extinguished via processes operating at more than one site, one in the cerebellum
      and one upstream in forebrain. The relative contributions of these sites may vary
      from animal to animal and situation to situation.

PMID- 21940610
TI  - Adaptive control of grip force to compensate for static and dynamic torques
      during object manipulation.
AB  - Manipulating a cup by the handle requires compensating for the torque induced by
      the moment of the mass of the cup relative to the location of the handle. In the
      present study, we investigated the control strategy of subjects asked to perform
      grip-lift movements with an object with center of mass located away from the grip
      axis. Participants were asked to lift the manipulandum with a two-fingers
      precision grip and stabilize it in front of a visual target. Subjects showed a
      gradual and slow adaptation of the grip-force scaling across trials: the grip
      force tended to decrease slowly, and the temporal coordination between grip-force
      and load-torque rates displayed gradually, better-coordinated patterns.
      Importantly, this adaptation was much slower than the stabilization of the same
      parameters measured either when no torque came into play or after previous
      adaptation to the presence of a torque. In contrast, the maximum rotation induced
      by the torque was controlled efficiently after only few trials, and an unexpected
      decrease in the tangential torque produced significant overcompensation. An
      unexpected increase in torque produced a consistent opposite effect. This shows
      that the compensation for the dynamic torque was based on an anticipatory,
      dynamic counter-torque produced by the arm and wrist motor commands. The
      comparatively slow stabilization of grip-force control suggests a specific
      adaptation process engaged by the presence of the torque. This paradigm,
      including tangential torques, clearly constitutes a powerful tool to extract the
      adaptive component of grip control during object manipulation.

PMID- 21940609
TI  - Sparse and dense coding of natural stimuli by distinct midbrain neuron
      subpopulations in weakly electric fish.
AB  - While peripheral sensory neurons respond to natural stimuli with a broad range of
      spatiotemporal frequencies, central neurons instead respond sparsely to specific
      features in general. The nonlinear transformations leading to this emergent
      selectivity are not well understood. Here we characterized how the neural
      representation of stimuli changes across successive brain areas, using the
      electrosensory system of weakly electric fish as a model system. We found that
      midbrain torus semicircularis (TS) neurons were on average more selective in
      their responses than hindbrain electrosensory lateral line lobe (ELL) neurons.
      Further analysis revealed two categories of TS neurons: dense coding TS neurons
      that were ELL-like and sparse coding TS neurons that displayed selective
      responses. These neurons in general responded to preferred stimuli with few
      spikes and were mostly silent for other stimuli. We further investigated whether
      information about stimulus attributes was contained in the activities of ELL and
      TS neurons. To do so, we used a spike train metric to quantify how well stimuli
      could be discriminated based on spiking responses. We found that sparse coding TS
      neurons performed poorly even when their activities were combined compared with
      ELL and dense coding TS neurons. In contrast, combining the activities of as few
      as 12 dense coding TS neurons could lead to optimal discrimination. On the other
      hand, sparse coding TS neurons were better detectors of whether their preferred
      stimulus occurred compared with either dense coding TS or ELL neurons. Our
      results therefore suggest that the TS implements parallel detection and
      estimation of sensory input.

PMID- 21940611
TI  - Sensorimotor integration for multisegmental frontal plane balance control in
      humans.
AB  - To quantify the contribution of sensory information to multisegmental frontal
      plane balance control in humans, we developed a feedback control model to account
      for experimental data. Subjects stood with feet close together on a surface that
      rotated according to a pseudorandom waveform at three different amplitudes.
      Experimental frequency-response functions and impulse-response functions were
      measured to characterize lower body (LB) and upper body (UB) motion evoked during
      surface rotations while subjects stood with eyes open or closed. The model
      assumed that corrective torques in LB and UB segments were generated with no time
      delay from intrinsic musculoskeletal mechanisms and with time delay from sensory
      feedback mechanisms. It was found that subjects' LB control was primarily based
      on sensory feedback. Changes in the LB control mechanisms across stimulus
      amplitude were consistent with the hypothesis that sensory reweighting
      contributed to amplitude-dependent changes in balance responses whereby subjects
      decreased reliance on proprioceptive cues that oriented the LB toward the surface
      and increased reliance on vestibular/visual cues that oriented the LB upright
      toward earth vertical as stimulus amplitude increased in both eyes open and
      closed conditions. Sensory reweighting in the LB control system also accounted
      for most of the amplitude-dependent changes observed in UB responses. In contrast
      to the LB system, sensory reweighting was not a dominant mechanism of UB control,
      and UB control was more influenced by intrinsic musculoskeletal mechanisms. The
      proposed model refines our understanding of sensorimotor integration during
      balance control by including multisegmental motion and explaining how
      intersegmental interactions influence frontal plane balance responses.

PMID- 21940612
TI  - Muscle ultrasound detects fasciculations and facilitates diagnosis in ALS.

PMID- 21940613
TI  - Risk factors, inpatient care, and outcomes of pneumonia after ischemic stroke.
AB  - OBJECTIVES: Pneumonia is the most common medical complication after stroke.
      Although several risk factors have been reported, the role of common
      comorbidities in the development of pneumonia is not well established. Moreover,
      there is discrepancy in the literature regarding the impact of pneumonia on
      stroke outcomes. METHODS: This is a multicenter retrospective cohort study
      including consecutive patients with ischemic stroke admitted to Regional Stroke
      Centers participating in the Registry of Canadian Stroke Network in July 2003
      March 2007. Pneumonia was defined as a complication that occurred within the
      first 30 days of the stroke and was confirmed radiographically. The main outcome
      measure was adjusted 30-day mortality. Secondary outcomes were adjusted 7- and
      365-day mortality, institutionalization, length of stay, and modified Rankin
      score on discharge. We also assessed the impact of organized stroke care on
      pneumonia development and mortality. RESULTS: Overall, 8,251 patients were
      included in the study. Stroke-associated pneumonia was observed in 587 patients
      (7.1%). Pneumonia increased 30-day (odds ratio [OR] 2.2 [95% confidence interval
      (CI) 1.8-2.7]) and 1-year mortality (OR 3.0 [95% CI 2.5-3.7]), but not 7-day
      mortality. Pneumonia was associated with poor functional outcome. Higher access
      to organized inpatient care resulted in a reduction of 30-day mortality (OR 0.50
      [95% CI 0.41-0.61]). Older age, male sex, stroke severity, dysphagia, chronic
      obstructive pulmonary disease, coronary artery disease, nonlacunar ischemic
      stroke, and preadmission dependency were independent predictors of pneumonia.
      CONCLUSIONS: Development of pneumonia after stroke was associated with mortality
      at 30 days and 1 year, longer length of stay, and dependency at discharge.
      Patients who received more inpatient stroke services had reduced mortality after
      pneumonia.

PMID- 21940614
TI  - Family history of neurodegenerative and vascular diseases in ALS: a population
      based study.
AB  - OBJECTIVE: To determine whether the frequency of Parkinson disease (PD),
      dementia, and vascular diseases in relatives of patients with amyotrophic lateral
      sclerosis (ALS) differs from the frequency of those diseases in relatives of
      controls, providing further information about the association between these
      diseases. METHODS: We studied the occurrence of neurodegenerative and vascular
      diseases in families of patients with ALS in a prospective, population-based,
      case-control study in the Netherlands between 2006 and 2009, using the recurrence
      risk lambda. Family history data were obtained by asking participants to fill in
      questionnaires. RESULTS: A total of 635 patients and 1,616 controls were
      included. The frequency of dementia was mildly increased only among parents and
      siblings of patients with sporadic ALS (lambda1.32; 95 confidence interval [CI]
      1.10-1.59), not among grandparents, or aunts and uncles. The risk of PD was not
      elevated (any relative: lambda 0.91; 95% CI 0.70-1.17). Among relatives of
      patients with familial ALS, no significantly increased risk of neurodegenerative
      diseases was found. A reduced risk of vascular diseases was found in relatives of
      patients with sporadic ALS (stroke: lambda 0.90; 95% CI 0.80-1.01 and myocardial
      infarction: lambda 0.86; 95% CI 0.79-0.94), and in relatives of patients with
      familial ALS (stroke: lambda 0.88; 95% CI 0.61-1.27 and myocardial infarction:
      lambda 0.61; 95% CI 0.43-0.86). CONCLUSIONS: This large, prospective, population
      based study showed that familial aggregation of ALS, dementia, and PD is
      substantially lower than previously thought. The lowered risk of vascular
      diseases in relatives of patients with ALS supports the view that a beneficial
      vascular risk profile increases ALS susceptibility.

PMID- 21940615
TI  - Infantile convulsions and paroxysmal kinesigenic dyskinesia with 16p11.2
      microdeletion.

PMID- 21940616
TI  - Arterial spin labeling and altered cerebral blood flow patterns in the minimally
      conscious state.
AB  - OBJECTIVE: To use arterial spin labeling (ASL) to compare cerebral blood flow
      (CBF) patterns in minimally conscious state (MCS) patients with those in normal
      controls in an observational study design. METHODS: Subjects meeting MCS criteria
      and normal controls were identified. A pseudocontinuous ASL sequence was
      performed with subjects and controls in the resting awake state. Multiple CBF
      values for 10 predetermined regions of interest were sampled and average CBF was
      calculated and compared between controls and subjects. RESULTS: Ten normal
      controls were identified, with ages ranging from 26 to 54 years. Four subjects
      met the MCS criteria and received an ASL study, with one patient receiving a
      second study at a later date. Subjects ranged in age from 19 to 58 years and had
      traumatic brain injury, stroke, or hypoxic-ischemic encephalopathy. Regional CBF
      for controls ranged from 21.6 to 57.2 mL/100 g/min, with a pattern of relatively
      increased blood flow posteriorly including the posterior cingulate, parietal, and
      occipital cortices. CBF patterns for MCS subjects showed greater variability
      (from 7.7 to 33.1 mL/100 g/min), demonstrating globally decreased CBF in gray
      matter compared with that in normal controls, especially in the medial prefrontal
      and midfrontal regions. In the one subject studied longitudinally, global CBF
      values increased over time, which correlated with clinical improvement.
      CONCLUSIONS: We identified globally decreased CBF and a selective reduction of
      CBF within the medial prefrontal and midfrontal cortical regions as well as gray
      matter in MCS patients. ASL may serve as an adjunctive method to assess
      functional reserve in patients recovering from severe brain injuries.

PMID- 21940617
TI  - Presymptomatic spinal cord neurometabolic findings in SOD1-positive people at
      risk for familial ALS.
AB  - OBJECTIVE: It has been speculated that amyotrophic lateral sclerosis (ALS) is
      characterized by a premanifest period during which neurodegeneration precedes the
      appearance of clinical manifestations. Magnetic resonance spectroscopy (MRS) was
      used to measure ratios of neurometabolites in the cervical spine of asymptomatic
      individuals with a mutation in the SOD1 gene (SOD1+) and compare their
      neurometabolic ratios to patients with ALS and healthy controls. METHODS: A cross
      sectional study of (1)H-MRS of the cervical spine was performed on 24
      presymptomatic SOD1+ volunteers, 29 healthy controls, and 23 patients with ALS.
      All presymptomatic subjects had no symptoms of disease, normal forced vital
      capacity, and normal electromyographic examination. Relative concentrations of
      choline (Cho), creatine (Cr), myo-inositol (Myo), and N-acetylaspartate (NAA)
      were determined. RESULTS: NAA/Cr and NAA/Myo ratios are reduced in both SOD1+
      subjects (39.7%, p = 0.001 and 18.0%, p = 0.02) and patients with ALS (41.2%, p <
      0.001 and 24.0%, p = 0.01) compared to controls. Myo/Cr is reduced (10.3%, p =
      0.02) in SOD1+ subjects compared to controls, but no difference was found between
      patients with ALS and controls. By contrast, NAA/Cho is reduced in patients with
      ALS (24.0%, p = 0.002), but not in presymptomatic SOD1+ subjects compared to
      controls. CONCLUSIONS: Changes in neurometabolite ratios in the cervical spinal
      cord are evident in presymptomatic SOD1+ individuals in advance of symptoms and
      clinical or electromyographic signs of disease. These changes reflect a reduction
      in NAA/Cr and NAA/Myo. Neurometabolic changes in this population resemble changes
      observed in patients with clinically apparent ALS. This suggests that
      neurometabolic changes occur early in the course of the disease process.

PMID- 21940618
TI  - Congruence and discrepancy of interictal and ictal EEG with MRI lesions in focal
      epilepsies.
AB  - OBJECTIVE: To compare the occurrence and localization of interictal epileptiform
      discharges (IEDs) and epileptic seizure patterns (ESPs) with the localization of
      MRI lesions. METHODS: We retrospectively analyzed the EEG and MRI data of a
      series of patients with focal epilepsies that had been studied from 1991 to 2009.
      RESULTS: In patients with temporal lesions, the localization of IEDs was most
      congruent (58.6% with IEDs exclusively over the lesional lobe and 29.7% with a
      majority of temporal IEDs). This differed (p < 0.001) from frontal lesions (27.5%
      with exclusively frontal IEDs, 24.6% with a majority of frontal IEDs). In parieto
      occipital lobe lesions, only 12.1% had IEDs exclusively over the lesional lobe
      compared to 48.5% with no parieto-occipital IEDs at all. Patients with central
      lesions often lacked any IEDs (54.5%, p < 0.001). The occurrence and localization
      of ESPs also differed between the regions. They were most congruent in temporal
      lesions (63.5% of patient had ESPs only over the lesional lobe, 23.4% had the
      majority of ESPs over the lesional lobe), which differed from frontal and parieto
      occipital lesions (37.7% and 30.3% of patients with ESPs only over the lesional
      lobe). Patients with central lesions had ESPs very frequently only outside the
      lesional lobe (63.6%). Surgery outcome did not differ between the regions.
      CONCLUSIONS: The occurrence and localization of interictal and ictal EEG findings
      differs vastly for lesions in different brain regions. These findings should be
      used to carefully weigh the results from EEG studies particularly in patients
      with extratemporal epilepsies considered for epilepsy surgery.

PMID- 21940619
TI  - Ultrasonographic detection of fasciculations markedly increases diagnostic
      sensitivity of ALS.
AB  - OBJECTIVES: To study the utility of muscle ultrasound (US) for detection of
      fasciculations and its contribution to diagnosis in amyotrophic lateral sclerosis
      (ALS). Fasciculations are characteristic features of ALS, and US can detect them
      easily and reliably. New diagnostic criteria for ALS, the Awaji algorithm,
      reintroduced fasciculations as evidence of acute denervation equivalent to that
      of fibrillations and positive sharp waves. METHODS: In 81 consecutive patients
      with sporadic ALS, we prospectively performed needle EMG and US in 6 muscles
      (tongue, biceps brachii, first dorsalis interosseous, paraspinalis, vastus
      lateralis, and tibialis anterior), and diagnostic category were determined by
      revised El Escorial criteria and Awaji criteria. RESULTS: Fasciculations were
      much more frequently detected by US than by EMG in the tongue (60% vs 0%), biceps
      brachii (88% vs 60%), and tibialis anterior muscles (83% vs 45%). The proportion
      of the patients with definite or probable ALS was 48% by revised El Escorial
      criteria and 79% by Awaji criteria using US. CONCLUSIONS: Muscle US is a
      practical and efficient tool to detect fasciculations, particularly in the
      tongue. A combination of US and EMG substantially increases the diagnostic
      sensitivity of ALS.

PMID- 21940620
TI  - I am conscious: Mr ASL says so.

PMID- 21940621
TI  - Mild cognitive impairment in drug-naive patients with PD is associated with
      cerebral hypometabolism.
AB  - OBJECTIVE: To characterize brain metabolic changes associated with mild cognitive
      impairment (MCI) in drug-naive patients with Parkinson disease (PD) using (18)F
      fluorodeoxyglucose (FDG) and PET (FDG-PET). METHODS: This cross-sectional study
      included newly diagnosed patients with PD with MCI in single or multiple domain
      (PD-MCI; n =12) and without MCI (PD-nMCI; n =12), and healthy controls (n =12).
      The groups were matched for age. Moreover, the patient groups were matched for
      motor disability. All subjects underwent a FDG-PET study. Cerebral regional
      relative metabolic maps were compared in PD-MCI, PD-nMCI, and controls using
      regions of interest analysis (ROIs) and voxel-based analysis with statistical
      parametric mapping. RESULTS: ROIs and voxel-based analyses revealed significant
      relative hypometabolism in the prefrontal, superior/inferior parietal, and
      associative occipital cortices as well as in the striatum in patients with PD-MCI
      relative to controls (p < 0.05) and to a lesser extent in patients with PD-nMCI.
      In contrast, patients with PD-nMCI did not show significant metabolic changes as
      compared to controls. CONCLUSION: MCI in patients with PD is associated with
      cortical hypometabolism since the earliest stage, independent of therapy or motor
      disability. The early involvement of posterior cortical region, a pattern shared
      by advanced stages of PD-MCI and PD with dementia, could represent an early
      marker of dementia. The relevance of this pattern in predicting prodromal
      dementia has to be evaluated in longitudinal studies.

PMID- 21940622
TI  - Modulating O2 reactivity in a fungal flavoenzyme: involvement of aryl-alcohol
      oxidase Phe-501 contiguous to catalytic histidine.
AB  - Aryl-alcohol oxidase (AAO) is a flavoenzyme responsible for activation of O(2) to
      H(2)O(2) in fungal degradation of lignin. The AAO crystal structure shows a
      buried active site connected to the solvent by a hydrophobic funnel-shaped
      channel, with Phe-501 and two other aromatic residues forming a narrow bottleneck
      that prevents the direct access of alcohol substrates. However, ligand diffusion
      simulations show O(2) access to the active site following this channel. Site
      directed mutagenesis of Phe-501 yielded a F501A variant with strongly reduced
      O(2) reactivity. However, a variant with increased reactivity, as shown by
      kinetic constants and steady-state oxidation degree, was obtained by substitution
      of Phe-501 with tryptophan. The high oxygen catalytic efficiency of F501W, ~2
      fold that of native AAO and ~120-fold that of F501A, seems related to a higher
      O(2) availability because the turnover number was slightly decreased with respect
      to the native enzyme. Free diffusion simulations of O(2) inside the active-site
      cavity of AAO (and several in silico Phe-501 variants) yielded >60% O(2)
      population at 3-4 A from flavin C4a in F501W compared with 44% in AAO and only
      14% in F501A. Paradoxically, the O(2) reactivity of AAO decreased when the access
      channel was enlarged and increased when it was constricted by introducing a
      tryptophan residue. This is because the side chain of Phe-501, contiguous to the
      catalytic histidine (His-502 in AAO), helps to position O(2) at an adequate
      distance from flavin C4a (and His-502 Nepsilon). Phe-501 substitution with a
      bulkier tryptophan residue resulted in an increase in the O(2) reactivity of this
      flavoenzyme.

PMID- 21940623
TI  - Prostaglandin E2 induces matrix metalloproteinase 9 expression in dendritic cells
      through two independent signaling pathways leading to activator protein 1 (AP-1)
      activation.
AB  - Dendritic Cells (DCs) play an important role in the initiation of the immune
      response by migrating to regional lymph nodes and presenting antigen processed at
      the inflammatory site to antigen-specific naive T cells. Prostaglandin E2 (PGE2)
      has been reported to play an essential role in DC migration. We reported
      previously that PGE2 induces matrix metalloproteinase 9 (MMP-9) expression in DCs
      and that PGE2-induced MMP-9 is required for DC migration in vivo and in vitro. In
      this study, we investigated the signaling mechanisms involved in PGE2-induced MMP
      9 expression in DCs. We show that PGE2-induced MMP-9 expression is mediated
      primarily through the EP2/EP4 -> cAMP -> protein kinase A (PKA)/PI3K -> ERK
      signaling pathway, leading to c-Fos expression, and through JNK-mediated
      activation of c-Jun in a PKA/PI3K/ERK-independent manner. EP2 and EP4 receptor
      agonists, as well as cAMP analogs, mimic the up-regulation of MMP-9 by PGE2. PKA,
      PI3K, and ERK inhibitors abolished PGE2- and cAMP-induced c-Fos and MMP-9 up
      regulation, and ERK activation was required for the binding of activator protein
      1 (AP-1) transcription factor to the MMP-9 promoter. Our results describe a new
      molecular mechanism for the effect of PGE2 on MMP-9 production in DCs that could
      lead to future therapeutic approaches using ERK inhibitors to regulate DC
      migration.

PMID- 21940624
TI  - Monitoring single-channel water permeability in polarized cells.
AB  - So far the determination of unitary permeability (p(f)) of water channels that
      are expressed in polarized cells is subject to large errors because the opening
      of a single water channel does not noticeably increase the water permeability of
      a membrane patch above the background. That is, in contrast to the patch clamp
      technique, where the single ion channel conductance may be derived from a single
      experiment, two experiments separated in time and/or space are required to obtain
      the single-channel water permeability p(f) as a function of the incremental water
      permeability (P(f,c)) and the number (n) of water channels that contributed to
      P(f,c). Although the unitary conductance of ion channels is measured in the
      native environment of the channel, p(f) is so far derived from reconstituted
      channels or channels expressed in oocytes. To determine the p(f) of channels from
      live epithelial monolayers, we exploit the fact that osmotic volume flow alters
      the concentration of aqueous reporter dyes adjacent to the epithelia. We measure
      these changes by fluorescence correlation spectroscopy, which allows the
      calculation of both P(f,c) and osmolyte dilution within the unstirred layer.
      Shifting the focus of the laser from the aqueous solution to the apical and
      basolateral membranes allowed the FCS-based determination of n. Here we validate
      the new technique by determining the p(f) of aquaporin 5 in Madin-Darby canine
      kidney cell monolayers. Because inhibition and subsequent activity rescue are
      monitored on the same sample, drug effects on exocytosis or endocytosis can be
      dissected from those on p(f).

PMID- 21940625
TI  - Molecular mechanisms of disease for mutations at Gly-90 in rhodopsin.
AB  - Two different mutations at Gly-90 in the second transmembrane helix of the
      photoreceptor protein rhodopsin have been proposed to lead to different
      phenotypes. G90D has been classically associated with congenital night blindness,
      whereas the newly reported G90V substitution was linked to a retinitis pigmentosa
      phenotype. Here, we used Val/Asp replacements of the native Gly at position 90 to
      unravel the structure/function divergences caused by these mutations and the
      potential molecular mechanisms of inherited retinal disease. The G90V and G90D
      mutants have a similar conformation around the Schiff base linkage region in the
      dark state and same regeneration kinetics with 11-cis-retinal, but G90V has
      dramatically reduced thermal stability when compared with the G90D mutant
      rhodopsin. The G90V mutant also shows, like G90D, an altered photobleaching
      pattern and capacity to activate Gt in the opsin state. Furthermore, the
      regeneration of the G90V mutant with 9-cis-retinal was improved, achieving the
      same A(280)/A(500) as wild type isorhodopsin. Hydroxylamine resistance was also
      recovered, indicating a compact structure around the Schiff base linkage, and the
      thermal stability was substantially improved when compared with the 11-cis
      regenerated mutant. These results support the role of thermal instability and/or
      abnormal photoproduct formation in eliciting a retinitis pigmentosa phenotype.
      The improved stability and more compact structure of the G90V mutant when it was
      regenerated with 9-cis-retinal brings about the possibility that this isomer or
      other modified retinoid analogues might be used in potential treatment strategies
      for mutants showing the same structural features.

PMID- 21940626
TI  - Maf1 protein, repressor of RNA polymerase III, indirectly affects tRNA
      processing.
AB  - Maf1 is negative regulator of RNA polymerase III in yeast. We observed high
      levels of both primary transcript and end-matured, intron-containing pre-tRNAs in
      the maf1Delta strain. This pre-tRNA accumulation could be overcome by
      transcription inhibition, arguing against a direct role of Maf1 in tRNA
      maturation and suggesting saturation of processing machinery by the increased
      amounts of primary transcripts. Saturation of the tRNA exportin, Los1, is one
      reason why end-matured intron-containing pre-tRNAs accumulate in maf1Delta cells.
      However, it is likely possible that other components of the processing pathway
      are also limiting when tRNA transcription is increased. According to our model,
      Maf1-mediated transcription control and nuclear export by Los1 are two major
      stages of tRNA biosynthesis that are regulated by environmental conditions in a
      coordinated manner.

PMID- 21940627
TI  - Endogenously expressed muscarinic receptors in HEK293 cells augment up-regulation
      of stably expressed alpha4beta2 nicotinic receptors.
AB  - Nicotine-induced up-regulation of neuronal nicotinic receptors (nAChRs) has been
      known and studied for more than 25 years. Other nAChR ligands can also up
      regulate nAChRs, but it is not known if these ligands induce up-regulation by
      mechanisms similar to that of nicotine. In this study, we compared up-regulation
      by three different nicotinic agonists and a competitive antagonist of several
      different nAChR subtypes expressed in HEK293 cells. Nicotine markedly increased
      alpha4beta2 nAChR binding site density and beta2 subunit protein. Carbachol, a
      known nAChR and muscarinic receptor agonist, up-regulated both alpha4beta2 nAChR
      binding sites and subunit protein 2-fold more than did nicotine. This increased
      up-regulation was shown pharmacologically to involve endogenously expressed
      muscarinic receptors, and stimulation of these muscarinic receptors also
      correlated with a 2-fold increase in alpha4 and beta2 mRNA. Muscarinic receptor
      activation in these cells appears to affect CMV promoter activity only minimally
      (~1.2 fold), suggesting that the increase in alpha4 and beta2 nAChR mRNA may not
      be dependent on enhanced transcription. Instead, other mechanisms may contribute
      to the increase in mRNA and a consequent increase in receptor subunits and
      binding site density. These studies demonstrate the possibility of augmenting
      nAChR expression in a cell model through mechanisms and targets other than the
      nAChR receptor itself.

PMID- 21940628
TI  - Mutually opposite signal modulation by hypothalamic heterodimerization of ghrelin
      and melanocortin-3 receptors.
AB  - Interaction and cross-talk of G-protein-coupled receptors (GPCRs) are of
      considerable interest because an increasing number of examples implicate a
      profound functional and physiological relevance of homo- or hetero-oligomeric
      GPCRs. The ghrelin (growth hormone secretagogue receptor (GHSR)) and melanocortin
      3 (MC3R) receptors are both known to have orexigenic effects on the hypothalamic
      control of body weight. Because in vitro studies indicate heterodimerization of
      GHSR and MC3R, we investigated their functional interplay. Combined in situ
      hybridization and immunohistochemistry indicated that the vast majority of GHSR
      expressing neurons in the arcuate nucleus also express MC3R. In vitro
      coexpression of MC3R and GHSR promoted enhanced melanocortin-induced
      intracellular cAMP accumulation compared with activation of MC3R in the absence
      of GHSR. In contrast, agonist-independent basal signaling activity and ghrelin
      induced signaling of GHSR were impaired, most likely due to interaction with
      MC3R. By taking advantage of naturally occurring GHSR mutations and an inverse
      agonist for GHSR, we demonstrate that the observed enhanced MC3R signaling
      capability depends directly on the basal activity of GHSR. In conclusion, we
      demonstrate a paradigm-shifting example of GPCR heterodimerization allowing for
      mutually opposite functional influence of two hypothalamic receptors controlling
      body weight. We found that the agonist-independent active conformation of one
      GPCR can determine the signaling modalities of another receptor in a heterodimer.
      Our discovery also implies that mutations within one of two interacting receptors
      might affect both receptors and different pathways simultaneously. These findings
      uncover mechanisms of important relevance for pharmacological targeting of GPCR
      in general and hypothalamic body weight regulation in particular.

PMID- 21940629
TI  - Glucocorticoids sensitize the innate immune system through regulation of the
      NLRP3 inflammasome.
AB  - Glucocorticoids have long been recognized as powerful anti-inflammatory compounds
      that are one of the most widely prescribed classes of drugs in the world.
      However, their role in the regulation of innate immunity is not well understood.
      We sought to examine the effects of glucocorticoids on the NOD-like receptors
      (NLRs), a central component of the inflammasome and innate immunity.
      Surprisingly, we show that glucocorticoids induce both NLRP3 messenger RNA and
      protein, which is a critical component of the inflammasome. The glucocorticoid
      dependent induction of NLRP3 sensitizes the cells to extracellular ATP and
      significantly enhances the ATP-mediated release of proinflammatory molecules,
      including mature IL-1beta, TNF-alpha, and IL-6. This effect was specific for
      glucocorticoids and dependent on the glucocorticoid receptor. These studies
      demonstrate a novel role for glucocorticoids in sensitizing the initial
      inflammatory response by the innate immune system.

PMID- 21940630
TI  - MicroRNA miR-21 regulates the metastatic behavior of B16 melanoma cells.
AB  - MicroRNA-21 (miR-21) is overexpressed in many human tumors and has been linked to
      various cellular processes altered in cancer. miR-21 is also up-regulated by a
      number of inflammatory agents, including IFN, which is of particular interest
      considering the close relationship between inflammation and cancer. Because miR
      21 appears to be overexpressed in human melanoma, we examined the role of miR-21
      in cancer development and metastasis in B16 mouse melanoma cells. We found that
      miR-21 is a member of an IFN-induced miRNA subset that requires STAT3 activation.
      To characterize the role of miR-21 in melanoma behavior, we transduced B16 cells
      with lentivirus encoding a miR-21 antagomir and isolated miR-21 knockdown B16
      cells. miR-21 knockdown or IFN treatment alone inhibited B16 cell proliferation
      and migration in vitro, and in combination they had an enhanced effect. Moreover,
      miR-21 knockdown sensitized B16 cells to IFN-induced apoptosis. In B16 cells miR
      21 targeted tumor suppressor (PTEN and PDCD4) and antiproliferative (BTG2)
      proteins. To characterize the role of miR-21 in vivo, empty vector- and antagomiR
      21-transduced B16 melanoma cells were injected via tail vein into syngeneic
      C57BL/6 mice. Although empty vector-transduced B16 cells produced large lung
      metastases, miR-21 knockdown cells only formed small lung lesions. Importantly,
      miR-21 knockdown tumor-bearing mice exhibited prolonged survival compared with
      empty vector tumor-bearing mice. Thus, miR-21 regulates the metastatic behavior
      of B16 melanoma cells by promoting cell proliferation, survival, and
      migration/invasion as well as by suppressing IFN action, providing important new
      insights into the role of miR-21 in melanoma.

PMID- 21940631
TI  - Cancer cells regulate biomechanical properties of human microvascular endothelial
      cells.
AB  - Metastasis is a key event of malignant tumor progression. The capability to
      metastasize depends on the ability of the cancer cell to migrate into connective
      tissue, adhere, and possibly transmigrate through the endothelium. Previously we
      reported that the endothelium does not generally act as barrier for cancer cells
      to migrate in three-dimensional extracellular matrices (3D-ECMs). Instead, the
      endothelium acts as an enhancer or a promoter for the invasiveness of certain
      cancer cells. How invasive cancer cells diminish the endothelial barrier function
      still remains elusive. Therefore, this study investigates whether invasive cancer
      cells can decrease the endothelial barrier function through alterations of
      endothelial biomechanical properties. To address this, MDA-MB-231 breast cancer
      cells were used that invade deeper and more numerous into 3D-ECMs when co
      cultured with microvascular endothelial cells. Using magnetic tweezer
      measurements, MDA-MB-231 cells were found to alter the mechanical properties of
      endothelial cells by reducing endothelial cell stiffness. Using spontaneous bead
      diffusion, actin cytoskeletal remodeling dynamics were shown to be increased in
      endothelial cells co-cultured with MDA-MB-231 cells compared with mono-cultured
      endothelial cells. In addition, knockdown of the alpha5 integrin subunit in
      highly transmigrating alpha5beta1(high) cells derived from breast, bladder, and
      kidney cancer cells abolished the endothelial invasion-enhancing effect
      comparable with the inhibition of myosin light chain kinase. These results
      indicate that the endothelial invasion-enhancing effect is alpha5beta1 integrin
      dependent. Moreover, inhibition of Rac-1, Rho kinase, MEK kinase, and PI3K
      reduced the endothelial invasion-enhancing effect, indicating that signaling via
      small GTPases may play a role in the endothelial facilitated increased
      invasiveness of cancer cells. In conclusion, decreased stiffness and increased
      cytoskeletal remodeling dynamics of endothelial cells may account for the
      breakdown of endothelial barrier function, suggesting that biomechanical
      alterations are sufficient to facilitate the transmigration and invasion of
      invasive cancer cells into 3D-ECMs.

PMID- 21940632
TI  - Enhanced activity of transforming growth factor beta1 (TGF-beta1) bound to
      cartilage oligomeric matrix protein.
AB  - Cartilage oligomeric matrix protein (COMP) is an important non-collagenous
      cartilage protein that is essential for the structural integrity of the cartilage
      extracellular matrix. The repeated modular structure of COMP allows it to
      "bridge" and assemble multiple cartilage extracellular matrix components such as
      collagens, matrilins, and proteoglycans. With its modular structure, COMP also
      has the potential to act as a scaffold for growth factors, thereby affecting how
      and when the growth factors are presented to cell-surface receptors. However, it
      is not known whether COMP binds growth factors. We studied the binding
      interaction between COMP and TGF-beta1 in vitro and determined the effect of COMP
      on TGF-beta1-induced signal transduction in reporter cell lines and primary
      cells. Our results demonstrate that mature COMP protein binds to multiple TGF
      beta1 molecules and that the peak binding occurs at slightly acidic pH. These
      interactions were confirmed by dual polarization interferometry and visualized by
      rotary shadow electron microscopy. There is cation-independent binding of TGF
      beta1 to the C-terminal domain of COMP. In the presence of manganese, an
      additional TGF-beta-binding site is present in the TSP3 repeats of COMP. Finally,
      we show that COMP-bound TGF-beta1 causes increased TGF-beta1-dependent
      transcription. We conclude that TGF-beta1 binds to COMP and that TGF-beta1 bound
      to COMP has enhanced bioactivity.

PMID- 21940633
TI  - Procollagen C-proteinase enhancer stimulates procollagen processing by binding to
      the C-propeptide region only.
AB  - Bone morphogenetic protein-1 (BMP-1) and the tolloid-like metalloproteinases
      control several aspects of embryonic development and tissue repair. Unlike other
      proteinases whose activities are regulated mainly by endogenous inhibitors,
      regulation of BMP-1/tolloid-like proteinases relies mostly on proteins that
      stimulate activity. Among these, procollagen C-proteinase enhancers (PCPEs)
      markedly increase BMP-1/tolloid-like proteinase activity on fibrillar
      procollagens, in a substrate-specific manner. Here, we performed a detailed
      quantitative study of the binding of PCPE-1 and of its minimal active fragment
      (CUB1-CUB2) to three regions of the procollagen III molecule: the triple helix,
      the C-telopeptide, and the C-propeptide. Contrary to results described elsewhere,
      we found the PCPE-1-binding sites to be located exclusively in the C-propeptide
      region. In addition, binding and enhancing activities were found to be
      independent of the glycosylation state of the C-propeptide. These data exclude
      previously proposed mechanisms for the action of PCPEs and also suggest new
      mechanisms to explain how these proteins can stimulate BMP-1/tolloid-like
      proteinases by up to 20-fold.

PMID- 21940634
TI  - Osteopontin signals through calcium and nuclear factor of activated T cells
      (NFAT) in osteoclasts: a novel RGD-dependent pathway promoting cell survival.
AB  - Osteopontin (OPN), an integrin-binding extracellular matrix glycoprotein,
      enhances osteoclast activity; however, its mechanisms of action are elusive. The
      Ca(2+)-dependent transcription factor NFATc1 is essential for osteoclast
      differentiation. We assessed the effects of OPN on NFATc1, which translocates to
      nuclei upon activation. Osteoclasts from neonatal rabbits and rats were plated on
      coverslips, uncoated or coated with OPN or bovine albumin. OPN enhanced the
      proportion of osteoclasts exhibiting nuclear NFATc1. An RGD-containing, integrin
      blocking peptide prevented the translocation of NFATc1 induced by OPN. Moreover,
      mutant OPN lacking RGD failed to induce translocation of NFATc1. Thus, activation
      of NFATc1 is dependent on integrin binding through RGD. Using fluorescence
      imaging, OPN was found to increase the proportion of osteoclasts exhibiting
      transient elevations in cytosolic Ca(2+) (oscillations). OPN also enhanced
      osteoclast survival. The intracellular Ca(2+) chelator 1,2-bis(O
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) suppressed Ca(2+)
      oscillations and inhibited increases in NFATc1 translocation and survival induced
      by OPN. Furthermore, a specific, cell-permeable peptide inhibitor of NFAT
      activation blocked the effects of OPN on NFATc1 translocation and osteoclast
      survival. This is the first demonstration that OPN activates NFATc1 and enhances
      osteoclast survival through a Ca(2+)-NFAT-dependent pathway. Increased NFATc1
      activity and enhanced osteoclast survival may account for the stimulatory effects
      of OPN on osteoclast function in vivo.

PMID- 21940636
TI  - Highlight: stability of mitochondrial membrane proteins in terrestrial
      vertebrates predicts aerobic capacity and longevity.

PMID- 21940635
TI  - Distinct roles for Rap1b protein in platelet secretion and integrin alphaIIbbeta3
      outside-in signaling.
AB  - Rap1b is activated by platelet agonists and plays a critical role in integrin
      alpha(IIb)beta(3) inside-out signaling and platelet aggregation. Here we show
      that agonist-induced Rap1b activation plays an important role in stimulating
      secretion of platelet granules. We also show that alpha(IIb)beta(3) outside-in
      signaling can activate Rap1b, and integrin outside-in signaling-mediated Rap1b
      activation is important in facilitating platelet spreading on fibrinogen and clot
      retraction. Rap1b-deficient platelets had diminished ATP secretion and P-selectin
      expression induced by thrombin or collagen. Importantly, addition of low doses of
      ADP and/or fibrinogen restored aggregation of Rap1b-deficient platelets.
      Furthermore, we found that Rap1b was activated by platelet spreading on
      immobilized fibrinogen, a process that was not affected by P2Y(12) or TXA(2)
      receptor deficiency, but was inhibited by the selective Src inhibitor PP2, the
      PKC inhibitor Ro-31-8220, or the calcium chelator demethyl-1,2-bis(2
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis. Clot retraction was
      abolished, and platelet spreading on fibrinogen was diminished in Rap1b-deficient
      platelets compared with wild-type controls. The defects in clot retraction and
      spreading on fibrinogen of Rap1b-deficient platelets were not rescued by addition
      of MnCl(2), which elicits alpha(IIb)beta(3) outside-in signaling in the absence
      of inside-out signaling. Thus, our results reveal two different activation
      mechanisms of Rap1b as well as novel functions of Rap1b in platelet secretion and
      in integrin alpha(IIb)beta(3) outside-in signaling.

PMID- 21940637
TI  - Short- and long-term evolutionary dynamics of bacterial insertion sequences:
      insights from Wolbachia endosymbionts.
AB  - Transposable elements (TE) are one of the major driving forces of genome
      evolution, raising the question of the long-term dynamics underlying their
      evolutionary success. Long-term TE evolution can readily be reconstructed in
      eukaryotes, thanks to many degraded copies constituting genomic fossil records of
      past TE proliferations. By contrast, bacterial genomes usually experience high
      sequence turnover and short TE retention times, thereby obscuring ancient TE
      evolutionary patterns. We found that Wolbachia bacterial genomes contain 52-171
      insertion sequence (IS) TEs. IS account for 11% of Wolbachia wRi, which is one of
      the highest IS genomic coverage reported in prokaryotes to date. We show that
      many IS groups are currently expanding in various Wolbachia genomes and that IS
      horizontal transfers are frequent among strains, which can explain the apparent
      synchronicity of these IS proliferations. Remarkably, >70% of Wolbachia IS are
      nonfunctional. They constitute an unusual bacterial IS genomic fossil record
      providing direct empirical evidence for a long-term IS evolutionary dynamics
      following successive periods of intense transpositional activity. Our results
      show that comprehensive IS annotations have the potential to provide new insights
      into prokaryote TE evolution and, more generally, prokaryote genome evolution.
      Indeed, the identification of an important IS genomic fossil record in Wolbachia
      demonstrates that IS elements are not always of recent origin, contrary to the
      conventional view of TE evolution in prokaryote genomes. Our results also raise
      the question whether the abundance of IS fossils is specific to Wolbachia or it
      may be a general, albeit overlooked, feature of prokaryote genomes.

PMID- 21940638
TI  - Loss-of-function mutation in a repressor module of human-specifically activated
      enhancer HACNS1.
AB  - The cis-regulatory element contributed to gaining humanness is of great interest
      in human evolutionary studies. A human-accelerated region exceeding neutral
      evolutionary rates, termed HACNS1, was recently reported as a positively selected
      sequence acquiring novel TF-binding sites responsible for human-specific gain of
      limb enhancer function. However, another possibility is loss of function in
      repressor element in HACNS1. Signature of the human substitutions in the 81-bp
      region infers that a GC-biased gene conversion (BGC) might create these seemingly
      excessive substitutions. To evaluate the 81-bp function, we performed transgenic
      mouse assay of the HACNS1 construct lacking the 81-bp region. The deleted
      construct showed similar enhancer activity to the intact human HACNS1, suggesting
      that the function of the human 81-bp region is not an activating enhancer but
      rather a disrupted repressor. This result infers that loss of function in the
      HACNS1 81-bp region, possibly via a BGC, played an important role in human
      specific evolution.

PMID- 21940640
TI  - Testing hypotheses about the sister group of the passeriformes using an
      independent 30-locus data set.
AB  - Although many phylogenetic studies have focused on developing hypotheses about
      relationships, advances in data collection and computation have increased the
      feasibility of collecting large independent data sets to rigorously test
      controversial hypotheses or carefully assess artifacts that may be misleading.
      One such relationship in need of independent evaluation is the position of
      Passeriformes (perching birds) in avian phylogeny. This order comprises more than
      half of all extant birds, and it includes one of the most important avian model
      systems (the zebra finch). Recent large-scale studies using morphology,
      mitochondrial, and nuclear sequence data have generated very different hypotheses
      about the sister group of Passeriformes, and all conflict with an older
      hypothesis generated using DNA-DNA hybridization. We used novel data from 30
      nuclear loci, primarily introns, for 28 taxa to evaluate five major a priori
      hypotheses regarding the phylogenetic position of Passeriformes. Although
      previous studies have suggested that nuclear introns are ideal for the resolution
      of ancient avian relationships, introns have also been criticized because of the
      potential for alignment ambiguities and the loss of signal due to saturation. To
      examine these issues, we generated multiple alignments using several alignment
      programs, varying alignment parameters, and using guide trees that reflected the
      different a priori hypotheses. Although different alignments and analyses yielded
      slightly different results, our analyses excluded all but one of the five a
      priori hypotheses. In many cases, the passerines were sister to the
      Psittaciformes (parrots), and taxa were members of a larger clade that includes
      Falconidae (falcons) and Cariamidae (seriemas). However, the position of
      Coliiformes (mousebirds) was highly unstable in our analyses of 30 loci, and this
      represented the primary source of incongruence among analyses. Mousebirds were
      united with passerines or parrots in some analyses, suggesting an additional
      hypothesis that needs to be considered in future studies. There was no clear
      evidence that base-compositional convergence, saturation, or long-branch
      attraction affected our conclusions. These results provide independent evidence
      excluding four major hypotheses about the position of passerines, allowing the
      extensive studies on this group to be placed in a more rigorous evolutionary
      framework.

PMID- 21940639
TI  - Temporally variable selection on proteolysis-related reproductive tract proteins
      in Drosophila.
AB  - In order to gain further insight into the processes underlying rapid reproductive
      protein evolution, we have conducted a population genetic survey of 44
      reproductive tract-expressed proteases, protease inhibitors, and targets of
      proteolysis in Drosophila melanogaster and Drosophila simulans. Our findings
      suggest that positive selection on this group of genes is temporally
      heterogeneous, with different patterns of selection inferred using tests
      sensitive at different time scales. Such variation in the strength and targets of
      selection through time may be expected under models of sexual conflict and/or
      host-pathogen interaction. Moreover, available functional information concerning
      the genes that show evidence of selection suggests that both sexual selection and
      immune processes have been important in the evolutionary history of this group of
      molecules.

PMID- 21940641
TI  - ImOSM: intermittent evolution and robustness of phylogenetic methods.
AB  - Among the criteria to evaluate the performance of a phylogenetic method,
      robustness to model violation is of particular practical importance as complete a
      priori knowledge of evolutionary processes is typically unavailable. For studies
      of robustness in phylogenetic inference, a utility to add well-defined model
      violations to the simulated data would be helpful. We therefore introduce ImOSM,
      a tool to imbed intermittent evolution as model violation into an alignment.
      Intermittent evolution refers to extra substitutions occurring randomly on
      branches of a tree, thus changing alignment site patterns. This means that the
      extra substitutions are placed on the tree after the typical process of sequence
      evolution is completed. We then study the robustness of widely used phylogenetic
      methods: maximum likelihood (ML), maximum parsimony (MP), and a distance-based
      method (BIONJ) to various scenarios of model violation. Violation of rates across
      sites (RaS) heterogeneity and simultaneous violation of RaS and the
      transition/transversion ratio on two nonadjacent external branches hinder all the
      methods recovery of the true topology for a four-taxon tree. For an eight-taxon
      balanced tree, the violations cause each of the three methods to infer a
      different topology. Both ML and MP fail, whereas BIONJ, which calculates the
      distances based on the ML estimated parameters, reconstructs the true tree.
      Finally, we report that a test of model homogeneity and goodness of fit tests
      have enough power to detect such model violations. The outcome of the tests can
      help to actually gain confidence in the inferred trees. Therefore, we recommend
      using these tests in practical phylogenetic analyses.

PMID- 21940642
TI  - Entangling ancient allotetraploidization in Asian Mitella: an integrated approach
      for multilocus combinations.
AB  - The reconstruction of an ancient polyploidization history is often challenging,
      although it is a crucial step in clarifying the mechanisms underlying the
      contemporary success and diversity of polyploids. Phylogenetic relationships of
      duplicated gene pairs of polyploids, with respect to their orthologs in related
      diploids, have been used to address this problem, but they often result in
      conflicting topologies among different genes. Asimitellaria is an East Asian
      endemic tetraploid lineage of perennials (genus Mitella; Saxifragaceae) that has
      diversified in riparian habitats. Phylogenetic analyses of four nuclear-encoded,
      single-copy (per haploid) genes GBSSI-A, GBSSI-B, GS-II, and PepCK all supported
      a single allopolyploid origin of Asimitellaria, but they did not lead to a
      consensus about which diploid lineage gave rise to each of the Asimitellaria
      subgenomes. To address this issue, we used an integrated approach, whereby the
      four gene data sets and an additional nuclear ribosomal external transcribed
      spacer and internal transcribed spacer (including a 5.8S ribosomal DNA) data set
      were concatenated in all possible combinations, and the most probable data
      combination was determined together with the phylogenetic inference. This
      resulted in relatively robust support for the two closely related North American
      diploid species as the ancestral lineages of the Asimitellaria subgenomes,
      suggesting ancient intercontinental migration of the diploid or tetraploid
      lineages and subsequent tetraploid diversification in the Japanese Archipelago.
      The present approach enabled sorting out the duplicated genes into their original
      combinations in their preduplication ancestors under a maximum-likelihood
      framework, and its extension toward genome sequencing data may help in the
      reconstruction of ancestral, preduplicated, whole-genome structures.

PMID- 21940643
TI  - Last of the human protists: the phylogeny and genetic diversity of Iodamoeba.
AB  - Iodamoeba is the last genus of obligately parasitic human protist whose
      phylogenetic position is unknown. Iodamoeba small subunit ribosomal DNA sequences
      were obtained using samples from three host species, and phylogenetic analyses
      convincingly placed Iodamoeba as a sister taxon to Endolimax. This clade in turn
      branches among free-living amoeboflagellates of the genus Mastigamoeba. Two
      Iodamoeba ribosomal lineages (RL1 and RL2) were detected whose sequences differ
      by 31%, each of which is found in both human and nonhuman hosts.

PMID- 21940644
TI  - Model averaging and Bayes factor calculation of relaxed molecular clocks in
      Bayesian phylogenetics.
AB  - We describe a procedure for model averaging of relaxed molecular clock models in
      Bayesian phylogenetics. Our approach allows us to model the distribution of rates
      of substitution across branches, averaged over a set of models, rather than
      conditioned on a single model. We implement this procedure and test it on
      simulated data to show that our method can accurately recover the true underlying
      distribution of rates. We applied the method to a set of alignments taken from a
      data set of 12 mammalian species and uncovered evidence that lognormally
      distributed rates better describe this data set than do exponentially distributed
      rates. Additionally, our implementation of model averaging permits accurate
      calculation of the Bayes factor(s) between two or more relaxed molecular clock
      models. Finally, we introduce a new computational approach for sampling rates of
      substitution across branches that improves the convergence of our Markov chain
      Monte Carlo algorithms in this context. Our methods are implemented under the
      BEAST 1.6 software package, available at http://beast-mcmc.googlecode.com.

PMID- 21940645
TI  - Deleterious mutation accumulation in asexual Timema stick insects.
AB  - Sexual reproduction is extremely widespread in spite of its presumed costs
      relative to asexual reproduction, indicating that it must provide significant
      advantages. One postulated benefit of sex and recombination is that they
      facilitate the purging of mildly deleterious mutations, which would accumulate in
      asexual lineages and contribute to their short evolutionary life span. To test
      this prediction, we estimated the accumulation rate of coding (nonsynonymous)
      mutations, which are expected to be deleterious, in parts of one mitochondrial
      (COI) and two nuclear (Actin and Hsp70) genes in six independently derived
      asexual lineages and related sexual species of Timema stick insects. We found
      signatures of increased coding mutation accumulation in all six asexual Timema
      and for each of the three analyzed genes, with 3.6- to 13.4-fold higher rates in
      the asexuals as compared with the sexuals. In addition, because coding mutations
      in the asexuals often resulted in considerable hydrophobicity changes at the
      concerned amino acid positions, coding mutations in the asexuals are likely
      associated with more strongly deleterious effects than in the sexuals. Our
      results demonstrate that deleterious mutation accumulation can differentially
      affect sexual and asexual lineages and support the idea that deleterious mutation
      accumulation plays an important role in limiting the long-term persistence of all
      female lineages.

PMID- 21940646
TI  - Effects of ranolazine on cloned cardiac kv4.3 potassium channels.
AB  - The effects of ranolazine, an antianginal drug, on potassium channel Kv4.3 were
      examined by using the whole-cell patch-clamp technique. Ranolazine inhibited the
      peak amplitude of Kv4.3 in a reversible, concentration-dependent manner with an
      IC(50) of 128.31 MUM. The activation kinetics were not significantly affected by
      ranolazine at concentrations up to 100 MUM. Applications of 10 and 30 MUM
      ranolazine had no effect on the fast and slow inactivation of Kv4.3. However, at
      concentrations of 100 and 300 MUM ranolazine caused a significant decrease in the
      rate of fast inactivation, and at a concentration of 300 MUM it caused a
      significant decrease in the rate of slow inactivation, resulting in a crossover
      of the current traces during depolarization. The Kv4.3 inhibition by ranolazine
      increased steeply between -20 and +20 mV. In the full activation voltage range,
      however, no voltage-dependent inhibition was found. Ranolazine shifted the
      voltage dependence of the steady-state inactivation of Kv4.3 in the
      hyperpolarizing direction in a concentration-dependent manner. The apparent
      dissociation constant (K(i)) for ranolazine for interacting with the inactivated
      state of Kv4.3 was calculated to be 0.32 MUM. Ranolazine produced little use
      dependent inhibition at frequencies of 1 and 2 Hz. Ranolazine did not affect the
      time course of recovery from the inactivation of Kv4.3. The results indicated
      that ranolazine inhibited Kv4.3 and exhibited a low affinity for Kv4.3 channels
      in the closed state but a much higher affinity for Kv4.3 channels in the
      inactivated state.

PMID- 21940648
TI  - Exposure to sublethal clinical radiotherapeutic doses of ionizing gamma-radiation
      gives rise to mutants of Gram-negative and Gram-positive clinical pathogens with
      increased antibiotic resistance.

PMID- 21940647
TI  - Estrogen increases nitric-oxide production in human bronchial epithelium.
AB  - Although sex differences in asthma severity are recognized, the mechanisms by
      which sex steroids such as estrogen influence the airway are still under
      investigation. Airway tone, a key aspect of asthma, represents a balance between
      bronchoconstriction and dilation. Nitric oxide (NO) from the bronchial epithelium
      is an endogenous bronchodilator. We hypothesized that estrogens facilitate
      bronchodilation by generating NO in bronchial epithelium. In acutely dissociated
      human bronchial epithelial cells from female patients exposure to 17beta
      estradiol (E(2); 10 pM-100 nM) resulted in rapid increase of diaminofluorescein
      fluorescence (NO indicator) within minutes, comparable with that induced by ATP
      (20 MUM). Estrogen receptor (ER) isoform-specific agonists (R,R)-5,11-diethyl
      5,6,11,12-tetrahydro-2,8-chrysenediol (THC) (ERalpha) and diaryl-propionitrile
      (DPN) (ERbeta) stimulated NO production to comparable levels and at comparable
      rates, whereas the ER antagonist 7alpha,17beta-[9-[(4,4,5,5,5
      pentafluoropentyl)sulfinyl]nonyl]estra-1,3,5(10)-triene-3,17-diol (ICI 182,780)
      (1 MUM) was inhibitory. Estrogen effects on NO were mediated via caveolin-1
      (blocked using the caveolin-1 scaffolding domain peptide) and by increased
      intracellular calcium concentration [prevented by 20 MUM 1,2-bis(o
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl) ester but not
      by blocking Ca(2+) influx using LaCl(3)]. Estrogen increased endothelial NO
      synthase activation (inhibited by 100 MUM N(G)-nitro-l-arginine methyl ester) and
      phosphorylated Akt. In epithelium-intact human bronchial rings contracted with
      acetylcholine (1 MUM), E(2), THC, and DPN all produced acute bronchodilation in a
      dose-dependent fashion. Such bronchodilatory effects were substantially reduced
      by epithelial denudation. Overall, these data indicate that estrogens, acting via
      ERalpha or ERbeta, can acutely produce NO in airway epithelium (akin to vascular
      endothelium). Estrogen-induced NO and its impairment may contribute to altered
      bronchodilation in women with asthma.

PMID- 21940649
TI  - Detection of clinically important beta-lactamases in commensal Escherichia coli
      of human and swine origin in western China.
AB  - Data correlating beta-lactamases found in commensal Escherichia coli of human and
      animal origin are limited. In this study, 447 commensal E. coli isolates from the
      faeces of humans and swine (280 human isolates from four hospitals and 167 swine
      isolates from seven farms) were collected between September 2006 and January 2009
      in western China. For extended-spectrum beta-lactamase (ESBL)-producing and other
      cephalosporin-resistant isolates, the relevant beta-lactamase genes (bla(TEM),
      bla(SHV), bla(CTX-M-1/2/9) group, bla(CMY-2) and bla(KPC)) were detected by PCR
      analysis. Of the 447 isolates tested, 120 (26.8 %) were confirmed as producing
      ESBL. Among these, 70 and 40 human isolates carried a member of the bla(CTX-M-1
      )group (13 bla(CTX-M-3), 21 bla(CTX-M-15), four bla(CTX-M-22), eight bla(CTX-M
      28), four bla(CTX-M-36), 15 bla(CTX-M-55) and five bla(CTX-M-69)) or bla(SHV) (14
      bla(SHV-2), seven bla(SHV-5), ten bla(SHV-12), five bla(SHV-57) and four bla(SHV
      97)),respectively, whilst six and four swine isolates carried a member of the
      bla(CTX-M-1 )group (one bla(CTX-M-15) and five bla(CTX-M-22)) or bla(SHV) (three
      bla(SHV-2) and one bla(SHV-12)), respectively. Furthermore, 59 human and swine
      isolates and seven human isolates carried bla(CMY-2) and bla(KPC), respectively.
      These findings indicate that the bla(CTX-M-1) group, including the novel variant
      bla(CTX-M-69), and bla(SHV) are the predominant ESBL genes in both humans and
      swine in western China, and bla(CMY-2) is also common in both groups. The
      carriage rates of broad-spectrum beta-lactamases among commensal E. coli was much
      lower in swine than in humans, suggesting that beta-lactamase genes have not
      established themselves in animal ecosystems in western China.

PMID- 21940650
TI  - Resistance to carbapenems in sequence type 11 Klebsiella pneumoniae is related to
      DHA-1 and loss of OmpK35 and/or OmpK36.
AB  - This study investigated the molecular mechanisms of carbapenem resistance in
      clinical isolates of Klebsiella pneumoniae from Korea and the clinical outcomes
      of resistant K. pneumoniae infection. Sixteen K. pneumoniae isolates showing
      resistance to carbapenems collected from a tertiary-care hospital were examined
      for the mechanisms of carbapenem resistance. PCR and sequencing experiments
      detected the bla(DHA-1) AmpC beta-lactamase gene in all 16 clinical isolates,
      whilst the bla genes of extended-spectrum beta-lactamases were detected in 12 of
      16 isolates. SDS-PAGE experiments indicated that all the isolates lacked the 35
      kDa and/or 36 kDa outer-membrane proteins (OMPs). Sequence analysis of the
      corresponding OMP genes revealed various alterations. PFGE analysis demonstrated
      that there were no major clonal relationships among the K. pneumoniae isolates.
      However, multilocus sequence typing experiments showed that all isolates shared
      the same sequence type (ST), ST11, except for one isolate of ST48. The crude
      mortality rate of infected patients was 81.8 %. Carbapenem resistance was mainly
      due to a combination of DHA-1 AmpC beta-lactamase coupled with the loss of OmpK35
      and/or OmpK36 and was associated with poor clinical outcome.

PMID- 21940651
TI  - Legionella longbeachae serogroup 1 infections linked to potting compost.
AB  - Four cases of legionellosis caused by Legionella longbeachae serogroup (sg) 1
      were identified in Scotland from 2008 to 2010. All case patients had exposure to
      commercially manufactured growing media or potting soils, commonly known as
      multipurpose compost (MPC), in greenhouse conditions, prior to disease onset. Two
      patients had been using the same brand of MPC but the clinical isolates were
      distinct genotypically by amplified fragment length polymorphism (AFLP) analysis.
      However, an indistinguishable AFLP profile was also found in an environmental
      isolate from the supply of MPC used by each patient. The third patient was
      diagnosed by immunofluorescent antibody serology only; however, the MPC to which
      this patient was exposed contained L. longbeachae sg 1 in large quantities (80
      000 c.f.u. g(-1)). The fourth patient was L. longbeachae sg 1 culture-positive,
      but L. longbeachae was not identified from 10 samples of garden composting
      material. As compost is commonly used, but L. longbeachae infection seemingly
      rare, further work is required to ascertain (i) the prevalence and predictors of
      L. longbeachae in compost and (ii) the conditions which facilitate transmission
      and generate an aerosol of the bacteria. As most cases of legionellosis are
      diagnosed by urinary antigen that is Legionella pneumophila-specific and does not
      detect infection with L. longbeachae, patients in cases of community-acquired
      pneumonia with a history of compost exposure should have serum and respiratory
      samples sent to a specialist Legionella reference laboratory for analysis.

PMID- 21940652
TI  - Clostridium clostridioforme liver abscess complicated by portal vein thrombosis
      in childhood.
AB  - Pyogenic liver abscesses are rare in children, and show geographical differences
      in their epidemiology. Mortality rates remain high at 15 %. Liver abscesses
      caused by anaerobic organisms are rare in a paediatric setting, even more so when
      complicated by portal vein thrombosis (PVT). A 6-year-old girl, previously fit
      and well, was admitted with fever, lethargy and weight loss of 2 weeks duration.
      The patient was febrile on examination and a review of the systems revealed no
      positive findings. An abdominal ultrasound scan showed multiple interconnecting
      cystic lesions consistent with liver abscesses, which was confirmed by a computed
      tomography scan. Aspirate of the abscess was cultured, resulting in the isolation
      of a non-haemolytic anaerobic organism, which was difficult to identify using
      conventional phenotypic identification tests. 16S rRNA typing identified the
      organism as Clostridium clostridioforme. The liver abscess in our patient
      displayed a particularly aggressive clinical course with extension of the abscess
      to involve the upper pole of the right kidney and the appendix, which was further
      complicated by PVT. The role of anaerobic organisms in liver abscesses has been
      underreported in the past. This case, therefore, highlights the importance of
      incubating biological samples in anaerobic conditions in order to adequately
      isolate and identify anaerobic bacteria, particularly those associated with
      abscesses.

PMID- 21940653
TI  - A case of scrub typhus with acalculous cholecystitis, aseptic meningitis and
      mononeuritis multiplex.
AB  - We present an unusual case of a patient with scrub typhus who developed
      acalculous cholecystitis, aseptic meningitis and mononeuritis multiplex. The
      patient was successfully treated with oral minocycline. To our knowledge, this is
      the first report of mononeuritis multiplex caused by scrub typhus.

PMID- 21940654
TI  - Sporobolomyces roseus in the cerebrospinal fluid of an immunocompetent patient-
      to treat or not to treat?
AB  - We present the case of an immunocompetent male who presented with symptoms of
      meningitis. Yeasts were seen in two consecutive cerebrospinal fluid samples,
      which were identified by PCR as Sporobolomyces roseus. This yeast is rarely
      encountered in clinical settings, and has only previously been seen to cause
      infection in immunocompromised patients. This case highlights the challenges
      presented by the identification of an unusual pathogen in an unexpected clinical
      setting.

PMID- 21940655
TI  - Identification of a plasmid-borne blaIMP-11 gene in clinical isolates of
      Escherichia coli and Klebsiella pneumoniae.
AB  - The acquired metallo-beta-lactamases represent a significant clinical threat due
      to their unrivalled hydrolysis spectrum and their resistance to therapeutic
      inhibitors of beta-lactamase. In this study, we identified plasmid- and integron
      borne bla(IMP-11) in clinical isolates of Escherichia coli and Klebsiella
      pneumoniae. The bla(IMP-11) gene cassette was carried by a typical class 1
      integron together with aacA1 and orfG gene cassettes. The integron, intI1-bla(IMP
      11)-aacA1-orfG-qacEDelta1-sul1, was easily transferred by intraspecies and
      intergenus conjugation of bacteria, indicating that the integron is located on a
      transferable plasmid. The integrated genes were preceded by TGGACA-N(17)-TAAACT,
      a hybrid P(c) promoter. Similar to the wild-type donors, the transconjugants also
      showed reduced susceptibility or resistance to carbapenems, amikacin and
      kanamycin. The identical integron was detected in four bacterial strains which
      were genetically different but were isolated from infant inpatients in the same
      paediatric department. These results demonstrate the colonization of the plasmid-
      and integron-borne bla(IMP-11) and aacA1 in the hospital environment,
      highlighting the importance of surveying and controlling the spread of such
      resistance determinants in nosocomial pathogens.

PMID- 21940656
TI  - Point: Put simply, standardization of cardiac troponin I is complicated.

PMID- 21940657
TI  - Counterpoint: Standardization of cardiac troponin I assays will not occur in my
      lifetime.

PMID- 21940658
TI  - Clopidogrel and CYP2C19 testing: ready for clinical prime time?

PMID- 21940659
TI  - Risk prediction with serial myeloperoxidase monitoring in patients with acute
      chest pain.
AB  - BACKGROUND: Although myeloperoxidase (MPO) monitoring is predictive for
      cardiovascular outcomes in suspected acute coronary syndromes, the value of
      serial testing is unknown. METHODS: We investigated the relationship between
      serial MPO concentrations in 490 individuals with acute chest pain and incident
      major adverse cardiac events (MACE) during 6 months of follow-up. We measured MPO
      with the CardioMPO assay, and cardiac troponin I (cTnI), with the Abbott
      Architect assay. RESULTS: Plasma MPO concentrations during the first 16 h were
      higher in individuals who experienced MACE. Higher MPO quartiles predicted a
      greater likelihood of 6-month MACE at baseline [OR (95% CI), 2.4 (1.4-4.1), P =
      0.001 for highest vs lowest quartile] and all subsequent time points, with
      strongest predictive ability found in 16-h postbaseline samples [9.9 (4.7-20.9),
      P < 0.001 for highest vs lowest quartile]. MPO was predictive for MACE among
      individuals whose cTnI remained within reference intervals (<0.028 MUg/L). The
      lowest rate of missed cases was found when MPO was <640 pmol/L at baseline and
      all other time points. Serial MPO monitoring predicted MACE risk better than
      baseline MPO measurements alone (c statistic 0.813 vs 0.602; P = 0.002),
      including in individuals whose cTnI remained within reference intervals (c
      statistic 0.903; P = 0.009). Combined serial cTnI and MPO testing improved
      accuracy for predicting 6-month MACE, reduced the number of missed MACE events
      from cTnI testing alone, and improved risk classification in 26.1% of patients.
      CONCLUSIONS: MPO concentrations are predictive of outcome up to 16 h after
      presentation with chest pain and predict events missed by cTnI testing,
      supporting a potential role in rapid patient triage.

PMID- 21940660
TI  - Hydrogen sulfide regulates cAMP homeostasis and renin degranulation in As4.1 and
      rat renin-rich kidney cells.
AB  - The present study aims to investigate the regulatory effect of hydrogen sulfide
      (H(2)S) on cAMP homeostasis and renin degranulation in As4.1 and rat renin-rich
      kidney cells. It was found in the present study that NaHS at 0.1-10 MUM
      significantly decreased cAMP production in As4.1 cells treated with isoproterenol
      (a beta-adrenoceptor agonist), forskolin (an adenylyl cyclase activator), or 3
      isobutyl-1-methylxanthine (IBMX, a phosphodiesterase inhibitor). NaHS at 10 MUM
      suppressed adenylate cyclase activity but stimulated phosphodiesterase activity.
      We continued to study whether H(2)S may mediate cAMP-dependent renin degranulaion
      in As4.1 cells. It was found that NaHS at 0.1-10 MUM significantly increased
      intracellular renin protein level. Moreover, NaHS reversed the declined renin
      content within As4.1 cells and normalized the upregulated renin activity in the
      culture medium of As4.1 cells treated with the above three stimuli. RT-PCR showed
      that cystathionine-gamma-lyase is the main enzyme to produce endogenous H(2)S in
      As4.1 cells. Overexpression of cystathionine-gamma-lyase increased endogenous
      H(2)S production and suppressed isoproterenol-induced renin release, suggesting
      that endogenous H(2)S may also inhibit renin release from As4.1 cells. We also
      tested whether H(2)S has a similar effect in renin-rich kidney cells. It was
      found that isoproterenol elevated intracellular cAMP level and extracellular
      renin activity but decreased renin protein level in the renin-rich kidney cells.
      Pretreatment with NaHS abolished these effects. In conclusion, H(2)S regulates
      cAMP homeostasis via inhibition of adenylate cyclase and stimulation of
      phosphodiesterase. Our findings suggest that H(2)S plays a critical role in
      regulation of renin degranulation in As4.1 and rat renin-rich kidney cells.

PMID- 21940661
TI  - Divergent CFTR orthologs respond differently to the channel inhibitors CFTRinh
      172, glibenclamide, and GlyH-101.
AB  - Comparison of diverse orthologs is a powerful tool to study the structure and
      function of channel proteins. We investigated the response of human, killifish,
      pig, and shark cystic fibrosis transmembrane conductance regulator (CFTR) to
      specific inhibitors of the channel: CFTR(inh)-172, glibenclamide, and GlyH-101.
      In three systems, including organ perfusion of the shark rectal gland, primary
      cultures of shark rectal gland tubules, and expression studies of each ortholog
      in cRNA microinjected Xenopus laevis oocytes, we observed fundamental differences
      in the sensitivity to inhibition by these channel blockers. In organ perfusion
      studies, shark CFTR was insensitive to inhibition by CFTR(inh)-172. This
      insensitivity was also seen in short-circuit current experiments with cultured
      rectal gland tubular epithelial cells (maximum inhibition 4 +/- 1.3%). In oocyte
      expression studies, shark CFTR was again insensitive to CFTR(inh)-172 (maximum
      inhibition 10.3 +/- 2.5% at 25 MUM), pig CFTR was insensitive to glibenclamide
      (maximum inhibition 18.4 +/- 4.4% at 250 MUM), and all orthologs were sensitive
      to GlyH-101. The amino acid residues considered responsible by previous site
      directed mutagenesis for binding of the three inhibitors are conserved in the
      four CFTR isoforms studied. These experiments demonstrate a profound difference
      in the sensitivity of different orthologs of CFTR proteins to inhibition by CFTR
      blockers that cannot be explained by mutagenesis of single amino acids. We
      believe that the potency of the inhibitors CFTR(inh)-172, glibenclamide, and GlyH
      101 on the CFTR chloride channel protein is likely dictated by the local
      environment and the three-dimensional structure of additional residues that form
      the vestibules, the chloride pore, and regulatory regions of the channel.

PMID- 21940662
TI  - Lymphatic function is regulated by a coordinated expression of lymphangiogenic
      and anti-lymphangiogenic cytokines.
AB  - Lymphangiogenic cytokines such as vascular endothelial growth factor-C (VEGF-C)
      are critically required for lymphatic regeneration; however, in some
      circumstances, lymphatic function is impaired despite normal or elevated levels
      of these cytokines. The recent identification of anti-lymphangiogenic molecules
      such as interferon-gamma (IFN-gamma), transforming growth factor-beta1, and
      endostatin has led us to hypothesize that impaired lymphatic function may
      represent a dysregulated balance in the expression of pro/anti-lymphangiogenic
      stimuli. We observed that nude mice have significantly improved lymphatic
      function compared with wild-type mice in a tail model of lymphedema. We show that
      gradients of lymphatic fluid stasis regulate the expression of lymphangiogenic
      cytokines (VEGF-A, VEGF-C, and hepatocyte growth factor) and that paradoxically
      the expression of these molecules is increased in wild-type mice. More
      importantly, we show that as a consequence of T-cell-mediated inflammation, these
      same gradients also regulate expression patterns of anti-lymphangiogenic
      molecules corresponding temporally and spatially with impaired lymphatic function
      in wild-type mice. We show that neutralization of IFN-gamma significantly
      increases inflammatory lymph node lymphangiogenesis independently of changes in
      VEGF-A or VEGF-C expression, suggesting that alterations in the balance of pro-
      and anti-lymphangiogenic cytokine expression can regulate lymphatic vessel
      formation. In conclusion, we show that gradients of lymphatic fluid stasis
      regulate not only the expression of pro-lymphangiogenic cytokines but also potent
      suppressors of lymphangiogenesis as a consequence of T-cell inflammation and that
      modulation of the balance between these stimuli can regulate lymphatic function.

PMID- 21940664
TI  - Structural selectivity of human SGLT inhibitors.
AB  - Human Na(+)-D-glucose cotransporter (hSGLT) inhibitors constitute the newest
      class of diabetes drugs, blocking up to 50% of renal glucose reabsorption in
      vivo. These drugs have potential for widespread use in the diabetes epidemic, but
      how they work at a molecular level is poorly understood. Here, we use
      electrophysiological methods to assess how they block Na(+)-D-glucose
      cotransporter SGLT1 and SGLT2 expressed in human embryonic kidney 293T (HEK-293T)
      cells and compared them to the classic SGLT inhibitor phlorizin. Dapagliflozin
      [(1S)-1,5,5-anhydro-1-C-{4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl}-D-glucitol],
      two structural analogs, and the aglycones of phlorizin and dapagliflozin were
      investigated in detail. Dapagliflozin and fluoro-dapagliflozin [(1S)-1,5-anhydro
      1-C-{4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl}-4-F-4-deoxy-D-glucitol] blocked
      glucose transport and glucose-coupled currents with ~100-fold specificity for
      hSGLT2 (K(i) = 6 nM) over hSGLT1 (K(i) = 400 nM). As galactose is a poor
      substrate for SGLT2, it was surprising that galacto-dapagliflozin [(1S)-1,5
      anhydro-1-C-{4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl}-D-galactitol] was a
      selective inhibitor of hSGLT2, but was less potent than dapagliflozin for both
      transporters (hSGLT2 K(i) = 25 nM, hSGLT1 K(i) = 25,000 nM). Phlorizin and
      galacto-dapagliflozin rapidly dissociated from SGLT2 [half-time off rate
      (t(1/2,Off)) ~ 20-30 s], while dapagliflozin and fluoro-dapagliflozin dissociated
      from hSGLT2 at a rate 10-fold slower (t(1/2,Off) >= 180 s). Phlorizin was unable
      to exchange with dapagliflozin bound to hSGLT2. In contrast, dapagliflozin,
      fluoro-dapagliflozin, and galacto-dapagliflozin dissociated quickly from hSGLT1
      (t(1/2,Off) = 1-2 s), and phlorizin readily exchanged with dapagliflozin bound to
      hSGLT1. The aglycones of phlorizin and dapagliflozin were poor inhibitors of both
      hSGLT2 and hSGLT1 with K(i) values > 100 MUM. These results show that inhibitor
      binding to SGLTs is composed of two synergistic forces: sugar binding to the
      glucose site, which is not rigid, and so different sugars will change the
      orientation of the aglycone in the access vestibule; and the binding of the
      aglycone affects the binding affinity of the entire inhibitor. Therefore, the
      pharmacophore must include variations in both the structure of the sugar and the
      aglycone.

PMID- 21940663
TI  - Enhanced store-operated Ca2+ entry and TRPC channel expression in pulmonary
      arteries of monocrotaline-induced pulmonary hypertensive rats.
AB  - Pulmonary hypertension (PH) is associated with profound vascular remodeling and
      alterations in Ca(2+) homeostasis in pulmonary arterial smooth muscle cells
      (PASMCs). Previous studies show that canonical transient receptor potential
      (TRPC) genes are upregulated and store-operated Ca(2+) entry (SOCE) is augmented
      in PASMCs of chronic hypoxic rats and patients of pulmonary arterial hypertension
      (PAH). Here we further examine the involvement of TRPC and SOCE in PH with a
      widely used rat model of monocrotaline (MCT)-induced PAH. Rats developed severe
      PAH, right ventricular hypertrophy, and significant increase in store-operated
      TRPC1 and TRPC4 mRNA and protein in endothelium-denuded pulmonary arteries (PAs)
      3 wk after MCT injection. Contraction of PA and Ca(2+) influx in PASMC evoked by
      store depletion using cyclopiazonic acid (CPA) were enhanced dramatically,
      consistent with augmented SOCE in the MCT-treated group. The time course of
      increase in CPA-induced contraction corresponded to that of TRPC1 expression.
      Endothelin-1 (ET-1)-induced vasoconstriction was also potentiated in PAs of MCT
      treated rats. The response was partially inhibited by SOCE blockers, including
      Gd(3+), La(3+), and SKF-96365, as well as the general TRPC inhibitor BTP-2,
      suggesting that TRPC-dependent SOCE was involved. Moreover, the ET-1-induced
      contraction and Ca(2+) response in the MCT group were more susceptible to the
      inhibition caused by the various SOCE blockers. Hence, our study shows that MCT
      induced PAH is associated with increased TRPC expression and SOCE, which are
      involved in the enhanced vascular reactivity to ET-1, and support the hypothesis
      that TRPC-dependent SOCE is an important pathway for the development of PH.

PMID- 21940665
TI  - Angiotensin II-NADPH oxidase-derived superoxide mediates diabetes-attenuated cell
      excitability of aortic baroreceptor neurons.
AB  - Overactivation of hyperpolarization-activated cyclic nucleotide-gated (HCN)
      channels is involved in diabetes-depressed excitability of aortic baroreceptor
      neurons in nodose ganglia. This involvement links to the autonomic dysfunction
      associated with high morbidity and mortality in diabetic patients. The present
      study examined the effects of an angiotensin II type I receptor (AT(1)R)
      antagonist (losartan), a NADPH oxidase inhibitor (apocynin), and a superoxide
      dismutase mimetic (tempol) on the enhanced HCN currents and attenuated cell
      excitability in diabetic nodose neurons. In sham and streptozotocin-induced type
      1 diabetic rats, HCN currents and cell excitability of aortic baroreceptor
      neurons were recorded by the whole cell patch-clamp technique. The angiotensin II
      level in nodose ganglia from diabetic rats was higher than that from sham rats
      (101.6 +/- 4.8 vs. 38.9 +/- 4.2 pg/mg protein, P < 0.05). Single-cell RT-PCR,
      Western blot, immunofluorescence staining, and chemiluminescence data showed that
      mRNA and protein expression of AT(1)R, protein expression of NADPH oxidase
      components, and superoxide production in nodose neurons were increased in
      diabetic rats compared with those from sham rats. HCN current density was higher
      and cell excitability was lower in aortic baroreceptor neurons from diabetic rats
      than that from sham rats. Losartan (1 MUM), apocynin (100 MUM), and tempol (1 mM)
      normalized the enhanced HCN current density and increased the cell excitability
      in the aortic baroreceptor neurons of diabetic rats. These findings suggest that
      endogenous angiotensin II-NADPH oxidase-superoxide signaling contributes to the
      enhanced HCN currents and the depressed cell excitation in the aortic
      baroreceptor neurons of diabetic rats.

PMID- 21940667
TI  - Ion channnels and transporters in cancer. 5. Ion channels in control of cancer
      and cell apoptosis.
AB  - Ion channels contribute to virtually all basic cellular processes, including such
      crucial ones for maintaining tissue homeostasis as proliferation,
      differentiation, and apoptosis. The involvement of ion channels in regulation of
      programmed cell death, or apoptosis, has been known for at least three decades
      based on observation that classical blockers of ion channels can influence cell
      death rates, prolonging or shortening cell survival. Identification of the
      central role of these channels in regulation of cell cycle and apoptosis as well
      as the recent discovery that the expression of ion channels is not limited solely
      to the plasma membrane, but may also include membranes of internal compartments,
      has led researchers to appreciate the pivotal role of ion channels plays in
      development of cancer. This review focuses on the aspects of programmed cell
      death influenced by various ion channels and how dysfunctions and misregulations
      of these channels may affect the development and progression of different
      cancers.

PMID- 21940666
TI  - Large-scale phosphotyrosine proteomic profiling of rat renal collecting duct
      epithelium reveals predominance of proteins involved in cell polarity
      determination.
AB  - Although extensive phosphoproteomic information is available for renal epithelial
      cells, previous emphasis has been on phosphorylation of serines and threonines
      with little focus on tyrosine phosphorylation. Here we have carried out large
      scale identification of phosphotyrosine sites in pervanadate-treated native inner
      medullary collecting ducts of rat, with a view towards identification of
      physiological processes in epithelial cells that are potentially regulated by
      tyrosine phosphorylation. The method combined antibody-based affinity
      purification of tyrosine phosphorylated peptides coupled with immobilized metal
      ion chromatography to enrich tyrosine phosphopeptides, which were identified by
      LC-MS/MS. A total of 418 unique tyrosine phosphorylation sites in 273 proteins
      were identified. A large fraction of these sites have not been previously
      reported on standard phosphoproteomic databases. All results are accessible via
      an online database: http://helixweb.nih.gov/ESBL/Database/iPY/. Analysis of
      surrounding sequences revealed four overrepresented motifs: [D/E]xxY*, Y*xxP,
      DY*, and Y*E, where the asterisk symbol indicates the site of phosphorylation.
      These motifs plus contextual information, integrated using the NetworKIN tool,
      suggest that the protein tyrosine kinases involved include members of the insulin
      and ephrin-receptor kinase families. Analysis of the gene ontology (GO) terms
      and KEGG pathways whose protein elements are overrepresented in our data set
      point to structures involved in epithelial cell-cell and cell-matrix interactions
      ("adherens junction," "tight junction," and "focal adhesion") and to components
      of the actin cytoskeleton as major sites of tyrosine phosphorylation in these
      cells. In general, these findings mesh well with evidence that tyrosine
      phosphorylation plays a key role in epithelial polarity determination.

PMID- 21940668
TI  - Doxorubicin acts via mitochondrial ROS to stimulate catabolism in C2C12 myotubes.
AB  - Doxorubicin, a commonly prescribed chemotherapeutic agent, causes skeletal muscle
      wasting in cancer patients undergoing treatment and increases mitochondrial
      reactive oxygen species (ROS) production. ROS stimulate protein degradation in
      muscle by activating proteolytic systems that include caspase-3 and the ubiquitin
      proteasome pathway. We hypothesized that doxorubicin causes skeletal muscle
      catabolism through ROS, causing upregulation of E3 ubiquitin ligases and caspase
      3. We tested this hypothesis by exposing differentiated C2C12 myotubes to
      doxorubicin (0.2 MUM). Doxorubicin decreased myotube width 48 h following
      exposure, along with a 40-50% reduction in myosin and sarcomeric actin. Cytosolic
      oxidant activity was elevated in myotubes 2 h following doxorubicin exposure.
      This increase in oxidants was followed by an increase in the E3 ubiquitin ligase
      atrogin-1/muscle atrophy F-box (MAFbx) and caspase-3. Treating myotubes with SS31
      (opposes mitochondrial ROS) inhibited expression of ROS-sensitive atrogin-1/MAFbx
      and protected against doxorubicin-stimulated catabolism. These findings suggest
      doxorubicin acts via mitochondrial ROS to stimulate myotube atrophy.

PMID- 21940669
TI  - Uncovering the pathway of sepsis-induced renal tubular dysfunction. Focus on
      "Basolateral LPS inhibits NHE3 and HCOFormula absorption through TLR4/MyD88
      dependent ERK activation in medullary thick ascending limb".

PMID- 21940670
TI  - Chronic AMPK stimulation attenuates adaptive signaling in dystrophic skeletal
      muscle.
AB  - In the present study, we evaluated how a pharmacologically induced phenotype
      shift in dystrophic skeletal muscle would affect subsequent intracellular
      signaling in response to a complementary, adaptive physiological stimulus. mdx
      mice were treated with the AMP-activated protein kinase (AMPK) activator 5
      aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR; 500 mg.kg(-1).day(
      1)) for 30 days, and then one-half of the animals were subjected to a bout of
      treadmill running to induce acute AMPK and p38 MAPK signaling. The mRNA levels of
      phenotypic modifiers, including peroxisome proliferator-activated receptor-delta
      (PPARdelta), PPARgamma coactivator-1alpha (PGC-1alpha), receptor interacting
      protein 140 (RIP 140), and silent information regulator two ortholog 1 (SIRT1)
      were assessed in skeletal muscle, as well as the expression of the protein
      arginine methyltransferase genes PRMT1 and CARM1. We found unique AMPK and p38
      phosphorylation and expression signatures between dystrophic and healthy muscle.
      In dystrophic skeletal muscle, treadmill running induced PPARdelta, PGC-1alpha,
      and SIRT1 mRNAs, three molecules that promote the slow, oxidative myogenic
      program. In the mdx animals that received the chronic AICAR treatment, running
      elicited AMPK and p38 phosphorylation was attenuated compared with vehicle
      treated mice. Similarly, acute stress-evoked expression of PPARdelta, PGC-1alpha,
      and SIRT1 was also blunted by chronic pharmacological AMPK stimulation. Skeletal
      muscle PRMT1 and CARM1 protein contents were higher in mdx mice compared with
      wild-type littermates. The acute running-evoked induction of PRMT1 and CARM1
      mRNAs was also attenuated by the AICAR treatment. Our data demonstrate that prior
      pharmacological conditioning is a salient determinant in how dystrophic muscle
      adapts to subsequent complementary, acute physiological stress stimuli. These
      results provide insight into possible therapeutic applications of synthetic
      agonists in neuromuscular diseases, such as during chronic administration to
      Duchenne muscular dystrophy patients.

PMID- 21940671
TI  - Extracellular chloride regulation of Kv2.1, contributor to the major outward Kv
      current in mammalian outer hair cells.
AB  - Outer hair cells (OHC) function as both receptors and effectors in providing a
      boost to auditory reception. Amplification is driven by the motor protein
      prestin, which is under anionic control. Interestingly, we now find that the
      major, 4-AP-sensitive, outward K(+) current of the OHC (I(K)) is also sensitive
      to Cl(-), although, in contrast to prestin, extracellularly. I(K) is inhibited by
      reducing extracellular Cl(-) levels, with a linear dependence of 0.4%/mM. Other
      voltage-dependent K(+) (Kv) channel conductances in supporting cells, such as
      Hensen and Deiters' cells, are not affected by reduced extracellular Cl(-). To
      elucidate the molecular basis of this Cl(-)-sensitive I(K), we looked at
      potential molecular candidates based on Cl(-) sensitivity and/or similarities in
      kinetics. For I(K), we identified three different Ca(2+)-independent components
      of I(K) based on the time constant of inactivation: a fast, transient outward
      current, a rapidly activating, slowly inactivating current (Ik(1)), and a slowly
      inactivating current (Ik(2)). Extracellular Cl(-) differentially affects these
      components. Because the inactivation time constants of Ik(1) and Ik(2) are
      similar to those of Kv1.5 and Kv2.1, we transiently transfected these constructs
      into CHO cells and found that low extracellular Cl(-) inhibited both channels
      with linear current reductions of 0.38%/mM and 0.49%/mM, respectively. We also
      tested heterologously expressed Slick and Slack conductances, two intracellularly
      Cl(-)-sensitive K(+) channels, but found no extracellular Cl(-) sensitivity. The
      Cl(-) sensitivity of Kv2.1 and its robust expression within OHCs verified by
      single-cell RT-PCR indicate that these channels underlie the OHC's extracellular
      Cl(-) sensitivity.

PMID- 21940673
TI  - Fine needle aspiration cytology of palpable and nonpalpable lymph nodes to detect
      metastatic melanoma.
AB  - BACKGROUND: Fine needle aspiration cytology (FNAC) is usually used to evaluate
      palpable nodes in patients with melanoma. The goal of our study is to review the
      sensitivity and specificity of this technique when applied to palpable but also
      to nonpalpable nodes. METHODS: FNAC was performed during 1984-2007 in 1279
      patients with suspicious lesions and/or lymph nodes. Indications for biopsy
      included increased size and/or palpability of nodes or abnormal ultrasound
      findings such as increased perfusion or focal lesions within the lymph nodes. The
      sensitivity, specificity, and positive and negative predictive values of FNACs
      guided by palpation or ultrasound were calculated for all patients and for
      subgroups of patients with palpable nodes or nonpalpable but sonomorphologically
      suspicious nodes. RESULTS: A total of 2446 FNACs were performed in 1279 melanoma
      patients, of which 2011 (82.2%) FNACs had clinically or histologically confirmed
      results. Increased size and/or palpability of nodes was observed in 376 (29.4%)
      of 1279 patients, and abnormal ultrasound findings occurred for 903 (70.6%),
      indicating that a biopsy was needed. FNACs guided by palpation had sensitivity,
      specificity, and positive and negative predictive values similar to that of FNACs
      guided by ultrasound (sensitivity = 98.4% vs 97.2%, specificity = 100% vs 99.8%,
      positive predictive value = 100% vs 99.9%, and negative predictive value = 95.2%
      vs 96.4%, for palpation-guided FNACs vs ultrasound-guided FNACs, respectively).
      Results did not differ between patients with the palpable nodes and patients with
      nonpalpable but sonomorphologically suspicious nodes. CONCLUSIONS: Ultrasound
      guided FNAC of suspicious lymph nodes and lesions in melanoma patients has a high
      sensitivity and specificity, and FNAC should not be limited to palpable nodes.
      FNAC of normal-sized nodes and/or lymph nodes with abnormal ultrasound findings
      can be used to identify early metastatic disease.

PMID- 21940672
TI  - IGF-I increases the expression of fibronectin by Nox4-dependent Akt
      phosphorylation in renal tubular epithelial cells.
AB  - Extracellular matrix accumulation contributes to the progression of chronic
      kidney disease. Many growth factors including insulin-like growth factor-I (IGF
      I) enhance matrix protein accumulation. Proximal tubular epithelial cells (PTCs)
      synthesize matrix proteins. NADPH oxidases are major sources of reactive oxygen
      species (ROS), important signaling molecules that mediate biological responses in
      a variety of cells and tissue. We investigated the mechanism by which IGF-I
      regulates fibronectin accumulation in PTCs and the role of a potential redox
      dependent signaling pathway. IGF-I induces an increase in NADPH-dependent
      superoxide generation, enhances the release of hydrogen peroxide, and increases
      the expression of NADPH oxidase 4 (Nox4) in PTCs. IGF-I also stimulates
      phosphorylation of Akt, and inhibition of Akt or its upstream activator
      phosphatidylinositol 3-kinase attenuates IGF-I-induced fibronectin accumulation.
      Expression of dominant negative Akt also inhibits IGF-I-induced expression of
      fibronectin, indicating a role for this kinase in fibronectin accumulation.
      Expression of dominant negative adenovirus Nox4 inhibits IGF-I-induced NADPH
      oxidase activity, Akt phosphorylation, and fibronectin protein expression.
      Moreover, transfection of small interfering RNA targeting Nox4 decreases Nox4
      protein expression and blocks IGF-I-induced Akt phosphorylation and the increase
      in fibronectin, placing Nox4 and ROS upstream of Akt signaling pathway. To
      confirm the role of Nox4, PTCs were infected with adenovirus construct expressing
      wild-type Nox4. Ad-Nox4, but not control Ad-green fluorescent protein,
      upregulated Nox4 expression and increased NADPH oxidase activity as well as
      fibronectin expression. Taken together, these results provide the first evidence
      for a role of Nox4 in IGF-I-induced Akt phosphorylation and fibronectin
      expression in tubular epithelial cells.

PMID- 21940674
TI  - Tripartite motif-containing protein 28 is a small ubiquitin-related modifier E3
      ligase and negative regulator of IFN regulatory factor 7.
AB  - IFN regulatory factor 7 (IRF7) is a potent transcription factor of type I IFNs
      and IFN-stimulated genes and is known as the master regulator of type I IFN
      dependent immune responses. Because excessive responses could harm the host, IRF7
      itself is delicately regulated at the transcriptional, translational, and
      posttranslational levels. Modification of IRF7 by small ubiquitin-related
      modifiers (SUMOs) has been shown to regulate IFN expression and antiviral
      responses negatively, but the specific E3 ligase needed for IRF7 SUMOylation has
      remained unknown. As reported in this article, we have identified the tripartite
      motif-containing protein 28 (TRIM28) as a binding partner of IRF7. We have
      demonstrated that TRIM28 also interacts with the SUMO E2 enzyme and increases
      SUMOylation of IRF7 both in vivo and in vitro, suggesting it acts as a SUMO E3
      ligase of IRF7. Unlike the common SUMO E3 ligase, protein inhibitor of activated
      STAT1, the E3 activity of TRIM28 is specific to IRF7, because it has little
      effect on IRF7's close relative IRF3. TRIM28 is therefore, so far as we know, the
      first IRF7-specific SUMO E3 reported. TRIM28-mediated SUMOylation of IRF7 is
      increased during viral infection, and SUMOylation of transcription factors
      usually results in transcriptional repression. Overexpression of TRIM28 therefore
      inhibits IRF7 transactivation activity, whereas knockdown of TRIM28 has the
      opposite effect and potentiates IFN production and antiviral responses.
      Collectively, our results suggest that TRIM28 is a specific SUMO E3 ligase and
      negative regulator of IRF7.

PMID- 21940675
TI  - Elevated tumor-associated antigen expression suppresses variant peptide vaccine
      responses.
AB  - Variant peptide vaccines are used clinically to expand T cells that cross-react
      with tumor-associated Ags (TAA). To investigate the effects of elevated
      endogenous TAA expression on variant peptide-induced responses, we used the GP70
      TAA model. Although young BALB/c mice display T cell tolerance to the TAA
      GP70(423-431) (AH1), expression of GP70 and suppression of AH1-specific responses
      increases with age. We hypothesized that as TAA expression increases, the AH1
      cross-reactivity of variant peptide-elicited T cell responses diminishes.
      Controlling for immunosenescence, we showed that elevated GP70 expression
      suppressed AH1 cross-reactive responses elicited by two AH1 peptide variants. A
      variant that elicited almost exclusively AH1 cross-reactive T cells in young mice
      elicited few or no T cells in aging mice with Ab-detectable GP70 expression. In
      contrast, a variant that elicited a less AH1 cross-reactive T cell response in
      young mice successfully expanded AH1 cross-reactive T cells in all aging mice
      tested. However, these T cells bound the AH1/MHC complex with a relatively short
      half-life and responded poorly to ex vivo stimulation with the AH1 peptide.
      Variant peptide vaccine responses were also suppressed when AH1 peptide is
      administered tolerogenically to young mice before vaccination. Analyses of
      variant-specific precursor T cells from naive mice with Ab-detectable GP70
      expression determined that these T cells expressed PD-1 and had downregulated IL
      7Ralpha expression, suggesting they were anergic or undergoing deletion. Although
      variant peptide vaccines were less effective as TAA expression increases, data
      presented in this article also suggest that complementary immunotherapies may
      induce the expansion of T cells with functional TAA recognition.

PMID- 21940676
TI  - CMRF-35-like molecule 3 preferentially promotes TLR9-triggered proinflammatory
      cytokine production in macrophages by enhancing TNF receptor-associated factor 6
      ubiquitination.
AB  - TLRs are critical innate immune sensors in the induction of proinflammatory
      cytokines to eliminate invading pathogens. However, the mechanisms for the full
      activation of TLR-triggered innate immune response need to be fully understood.
      The murine CMRF-35-like molecule (CLM)-3 is a representative of CLM family
      belonging to the Ig superfamily. Considering that CLM-3 is selectively expressed
      in macrophages and the roles of CLM members in innate immune response remain
      unclear, in this study we investigated the role of CLM-3 in the regulation of TLR
      triggered innate response. We found that CLM-3 was an endosome/lysosome-localized
      molecule, and was downregulated in macrophages by stimulation with TLR9 ligand,
      but not TLR4 and TLR3 ligands. Interestingly, CLM-3 selectively promoted
      production of TNF-alpha and IL-6 in macrophages triggered by TLR9, but not TLR4
      or TLR3. CLM-3 enhanced activation of MAPKs and NF-kappaB pathways in TLR9
      triggered macrophages. Furthermore, CLM-3-transgenic mice were generated, and CLM
      3 expression was confirmed by mAb against CLM-3 that we prepared. Accordingly,
      the macrophages derived from CLM-3-transgenic mice were more sensitive to TLR9
      ligand stimulation, with more pronounced production of TNF-alpha, IL-6, and
      increased activation of MAPKs and NF-kappaB pathways. Moreover, ubiquitination of
      TNFR-associated factor 6, a crucial signaling transducer of TLR-triggered MAPKs
      and NF-kappaB activation, was found to be significantly promoted by CLM-3 in
      macrophages. Collectively, the endosome/lysosome-localized CLM-3 can promote full
      activation of TLR9-triggered innate responses by enhancing TNFR-associated factor
      6 ubiquitination and subsequently activating MAPKs and NF-kappaB.

PMID- 21940677
TI  - Pathogenic autoreactive B cells are not negatively selected toward matrix protein
      collagen II.
AB  - We have addressed the importance of B cell tolerance to collagen type II, a
      matrix protein, which is a target in rheumatoid arthritis (RA) and its mouse
      models. We generated a germline-encoded anti-collagen type II (CII) IgH
      replacement anti-C1 B cell mouse strain (ACB) to investigate how B cell tolerance
      to CII, a matrix protein, is subverted and to further understand pathogenesis of
      RA. Phenotypic analysis revealed that CII-specific B cells were surprisingly
      neither deleted nor anergized. Instead, they were readily detected in all
      lymphoid organs. Spontaneously produced autoantibodies could bind directly to
      cartilage surface without detectable pathology. However, exaggerated arthritis
      was seen after injection of anti-CII Abs specific for other epitopes. In
      addition, Abs from CII-specific hybridomas generated from ACB mice induced
      arthritis. Interestingly, IgH/L chain sequence data in B cell hybridomas revealed
      a lack of somatic mutations in autoreactive B cells. The ACB model provides the
      first possibility, to our knowledge, to study B cell tolerance to a matrix
      protein, and the observations made in the study could not be predicted from
      previous models. B cell-reactive epitopes on CII are largely shared between human
      RA and rodent CII-induced arthritis; this study, therefore, has important
      implications for further understanding of pathological processes in autoimmune
      diseases like RA.

PMID- 21940678
TI  - The magnitude of the T cell response to a clinically significant dose of
      influenza virus is regulated by TRAIL.
AB  - An immune response of appropriate magnitude should be robust enough to control
      pathogen spread but not simultaneously lead to immunopathology. Primary infection
      with influenza A virus (IAV) results in a localized pulmonary infection and
      inflammation and elicits an IAV-specific CD8 T cell immune response necessary for
      viral clearance. Clearance of IAV-infected cells, and recovery from infection, is
      mediated by perforin/granzyme B- and Fas/FasL-mediated mechanisms. We recently
      reported that TRAIL is another means by which IAV-specific CD8 T cells can kill
      IAV-infected cells. The current study examined the role of TRAIL in the pulmonary
      CD8 T cell response to a clinically significant IAV [A/PR/8/34 (PR8; H1N1)]
      infection (i.e., leads to observable, but limited, morbidity and mortality in
      wild-type [WT] mice). Compared with WT mice, IAV-infected Trail(-/-) mice
      experienced increased morbidity and mortality despite similar rates of viral
      clearance from the lungs. The increased morbidity and mortality in Trail(-/-)
      mice correlated with increased pulmonary pathology and inflammatory chemokine
      production. Analysis of lung-infiltrating lymphocytes revealed increased numbers
      of IAV-specific CD8 T cells in infected Trail(-/-) mice, which correlated with
      increased pulmonary cytotoxic activity and increased pulmonary expression of MIG
      and MIP-1alpha. In addition, there was decreased apoptosis and increased
      proliferation of IAV-specific CD8 T cells in the lungs of Trail(-/-) mice
      compared with WT mice. Together, these data suggest that TRAIL regulates the
      magnitude of the IAV-specific CD8 T cell response during a clinically significant
      IAV infection to decrease the chance for infection-induced immunopathology.

PMID- 21940679
TI  - The NF-kappaB transcription factor c-Rel is required for Th17 effector cell
      development in experimental autoimmune encephalomyelitis.
AB  - Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated autoimmune
      disease involving effector Th subsets such as Th1 and Th17. In this study, we
      demonstrate that mice lacking the NF-kappaB transcription factor family member c
      Rel (rel(-/-)), which are known to be resistant to EAE, show impaired Th17
      development. Mixed bone marrow chimeras and EAE adoptive transfer experiments
      show that the deficiency of effector Th17 cells in rel(-/-) mice is T cell
      intrinsic. Consistent with this finding, c-Rel was activated in response to TCR
      signaling in the early stages of Th17 development and controlled the expression
      of Rorc, which encodes the Th17 transcription factor retinoic acid-related orphan
      receptor gammat. CD28, but not IL-2, repression of Th17 development was dependent
      on c-Rel, implicating a dual role for c-Rel in modulating Th17 development.
      Adoptive transfer experiments also suggested that c-Rel control of regulatory T
      cell differentiation and homeostasis influences EAE development and severity by
      influencing the balance between Th17 and regulatory T cells. Collectively, our
      findings indicate that in addition to promoting Th1 differentiation, c-Rel
      regulates the development and severity of EAE via multiple mechanisms that impact
      on the generation of Th17 cells.

PMID- 21940681
TI  - Next-generation mapping of complex traits with phenotype-based selection and
      introgression.
AB  - Finding the genes underlying complex traits is difficult. We show that new
      sequencing technology combined with traditional genetic techniques can
      efficiently identify genetic regions underlying a complex and quantitative
      behavioral trait. As a proof of concept we used phenotype-based introgression to
      backcross loci that control innate food preference in Drosophila simulans into
      the genomic background of D. sechellia, which expresses the opposite preference.
      We successfully mapped D. simulans introgression regions in a small mapping
      population (30 flies) with whole-genome resequencing using light coverage (~1*).
      We found six loci contributing to D. simulans food preference, one of which
      overlaps a previously discovered allele. This approach is applicable to many
      systems, does not rely on laborious marker development or genotyping, does not
      require existing high quality reference genomes, and needs only small mapping
      populations. Because introgression is used, researchers can scale mapping
      population size, replication, and number of backcross generations to their needs.
      Finally, in contrast to more widely used mapping techniques like F(2) bulk
      segregant analysis, our method produces near-isogenic lines that can be kept and
      reused indefinitely.

PMID- 21940680
TI  - Hemorrhagic shock activation of NLRP3 inflammasome in lung endothelial cells.
AB  - Hemorrhagic shock (HS) due to major trauma and surgery predisposes the host to
      the development of systemic inflammatory response syndrome (SIRS), including
      acute lung injury (ALI), through activating and exaggerating the innate immune
      response. IL-1beta is a crucial proinflammatory cytokine that contributes to the
      development of SIRS and ALI. Lung endothelial cells (EC) are one important source
      of IL-1beta, and the production of active IL-1beta is controlled by the
      inflammasome. In this study, we addressed the mechanism underlying HS activation
      of the inflammasome in lung EC. We show that high mobility group box 1 acting
      through TLR4, and a synergistic collaboration with TLR2 and receptor for advanced
      glycation end products signaling, mediates HS-induced activation of EC NAD(P)H
      oxidase. In turn, reactive oxygen species derived from NAD(P)H oxidase promote
      the association of thioredoxin-interacting protein with the nucleotide-binding
      oligomerization domain-like receptor protein NLRP3 and subsequently induce
      inflammasome activation and IL-1beta secretion from the EC. We also show that
      neutrophil-derived reactive oxygen species play a role in enhancing EC NAD(P)H
      oxidase activation and therefore an amplified inflammasome activation in response
      to HS. The present study explores a novel mechanism underlying HS activation of
      EC inflammasome and thus presents a potential therapeutic target for SIRS and ALI
      induced after HS.

PMID- 21940682
TI  - Quantitative trait locus analysis of stage-specific inbreeding depression in the
      Pacific oyster Crassostrea gigas.
AB  - Inbreeding depression and genetic load have been widely observed, but their
      genetic basis and effects on fitness during the life cycle remain poorly
      understood, especially for marine animals with high fecundity and high, early
      mortality (type-III survivorship). A high load of recessive mutations was
      previously inferred for the Pacific oyster Crassostrea gigas, from massive
      distortions of zygotic, marker segregation ratios in F(2) families. However, the
      number, genomic location, and stage-specific onset of mutations affecting
      viability have not been thoroughly investigated. Here, we again report massive
      distortions of microsatellite-marker segregation ratios in two F(2) hybrid
      families, but we now locate the causative deleterious mutations, using a
      quantitative trait locus (QTL) interval-mapping model, and we characterize their
      mode of gene action. We find 14-15 viability QTL (vQTL) in the two families.
      Genotypic frequencies at vQTL generally suggest selection against recessive or
      partially recessive alleles, supporting the dominance theory of inbreeding
      depression. No epistasis was detected among vQTL, so unlinked vQTL presumably
      have independent effects on survival. For the first time, we track segregation
      ratios of vQTL-linked markers through the life cycle, to determine their stage
      specific expression. Almost all vQTL are absent in the earliest life stages
      examined, confirming zygotic viability selection; vQTL are predominantly
      expressed before the juvenile stage (90%), mostly at metamorphosis (50%). We
      estimate that, altogether, selection on vQTL caused 96% mortality in these
      families, accounting for nearly all of the actual mortality. Thus, genetic load
      causes substantial mortality in inbred Pacific oysters, particularly during
      metamorphosis, a critical developmental transition warranting further
      investigation.

PMID- 21940684
TI  - Novel mutations in the C-terminal region of the MECP2 gene in Tunisian Rett
      syndrome patients.
AB  - Rett syndrome (RTT), an X-linked dominant neurodevelopmental disorder in females,
      is caused mainly by de novo mutations in the methyl-CpG-binding protein 2 gene
      (MECP2). Rett patients present an apparently normal psychomotor development
      during the first 6 to 18 months of life. Thereafter, they show a short period of
      developmental stagnation followed by a rapid regression in language and motor
      development. In the present study, we performed a mutational analysis of the
      MECP2 gene in 2 typical Rett syndrome patients and in 1 atypical Rett syndrome
      girl. The results showed the presence of 3 de novo point mutations in the C
      terminal region: 2 novel mutations: c.1065C>A (p.S355R) and c.1030C>G (p.R344G)
      in the 2 typical Rett syndrome girls, but also the c.996C>T (p.S332S) mutation
      first described in the atypical Rett syndrome patient.

PMID- 21940683
TI  - The Hsp70 and Hsp40 chaperones influence microtubule stability in Chlamydomonas.
AB  - Mutations at the APM1 and APM2 loci in the green alga Chlamydomonas reinhardtii
      confer resistance to phosphorothioamidate and dinitroaniline herbicides. Genetic
      interactions between apm1 and apm2 mutations suggest an interaction between the
      gene products. We identified the APM1 and APM2 genes using a map-based cloning
      strategy. Genomic DNA fragments containing only the DNJ1 gene encoding a type I
      Hsp40 protein rescue apm1 mutant phenotypes, conferring sensitivity to the
      herbicides and rescuing a temperature-sensitive growth defect. Lesions at five
      apm1 alleles include missense mutations and nucleotide insertions and deletions
      that result in altered proteins or very low levels of gene expression. The HSP70A
      gene, encoding a cytosolic Hsp70 protein known to interact with Hsp40 proteins,
      maps near the APM2 locus. Missense mutations found in three apm2 alleles predict
      altered Hsp70 proteins. Genomic fragments containing the HSP70A gene rescue apm2
      mutant phenotypes. The results suggest that a client of the Hsp70-Hsp40 chaperone
      complex may function to increase microtubule dynamics in Chlamydomonas cells.
      Failure of the chaperone system to recognize or fold the client protein(s)
      results in increased microtubule stability and resistance to the microtubule
      destabilizing effect of the herbicides. The lack of redundancy of genes encoding
      cytosolic Hsp70 and Hsp40 type I proteins in Chlamydomonas makes it a uniquely
      valuable system for genetic analysis of the function of the Hsp70 chaperone
      complex.

PMID- 21940685
TI  - A new tyrosine hydroxylase genotype associated with early-onset severe
      encephalopathy.
AB  - We describe a boy affected by an early-onset severe encephalopathy (stagnation of
      psychomotor development, paroxysmal dystonic postures and movements of limbs,
      hypokinesia) due to tyrosine hydroxylase deficiency. High blood prolactin and low
      homovanillic acid in cerebrospinal fluid suggested the diagnosis. Genetic
      analysis revealed 3 new missense mutations on tyrosine hydroxylase gene:
      [c.752C>T(p.P251L) and c.887G>A(p.R296Q] harbored by the father and c.836G>T
      (p.C279F) of maternal origin. Bioinformatics tools have been helpful in
      predicting the pathogenic role of p.P251L and p.C279F substitutions, while a weak
      pathogenic effect was ascribed to p.R296Q.

PMID- 21940687
TI  - Infantile Pompe disease: clinical and genetic characteristics with an experience
      of enzyme replacement therapy.
AB  - Pompe disease is an autosomal recessive disorder caused by lysosomal acid alpha
      glucosidase deficiency. Infantile-onset Pompe disease presents with
      cardiomyopathy and hypotonia, leading to premature death. This article describes
      7 infantile Pompe disease cases and provides their molecular bases and clinical
      outcomes after enzyme replacement therapy for the first time in Korea. Molecular
      genetic analyses revealed the presence of 9 different mutations, including 5
      novel mutations (c.2171C>A, c.2774C>T, c.1582_3de12, c.1261_1263Tms, and
      c.1322_1326+9de114). The most common mutation in these 7 patients was c.1316T>A
      (28%). Four patients received intravenous recombinant human acid alpha
      glucosidase therapy for 2 years, on average, without significant side effects
      during the treatment course. They all exhibited increased muscle power, with
      considerable improvement in cardiac function. Pompe disease is heterogeneous
      regarding both clinical features and molecular characteristics. Early
      identification of Pompe disease is very important, considering that enzyme
      replacement therapy is a safe and effective treatment for early-onset patients.

PMID- 21940688
TI  - Late infantile neuronal ceroid lipofuscinosis and dopamine deficiency.
AB  - Neuronal ceroid lipofuscinosis is a severe neurodegenerative lysosomal storage
      disorder. Gamma-aminobutyric acid and glutamate deficiency have been reported
      with CLN1, CLN3, and CLN6. Isolated biopterin/neopterin without dopamine
      deficiency has been reported in 1 patient with a CLN2 mutation. This report
      describes a patient with a CLN2 mutation with symptomatic biopterin and dopamine
      deficiency. A 4-year-old boy presented with intractable epilepsy and
      developmental regression starting 1 year previously. His exam showed retinopathy,
      scanning speech, dysmetria, and ataxic fenestrating gait with stooped posture.
      Electroencephalogram showed generalized spikes with occipital spikes on slow
      photic stimulation. Brain magnetic resonance images 1 year apart showed
      significant diffuse atrophy. CLN2 gene sequencing showed pathogenic compound
      heterozygous mutations. Cerebrospinal fluid neurotransmitters showed low
      homovanillic acid and tetrahydrobiopterin. Levodopa-carbidopa resulted in
      dramatic improvement of gait. Dopamine/biopterin deficiency is a possible
      secondary manifestation of CLN2 mutations. Levodopa and dopamine agonists might
      be useful in treating these secondary abnormalities and improving quality of life
      in these patients.

PMID- 21940689
TI  - Central nervous system herpes simplex virus infection in afebrile children with
      seizures.
AB  - Central nervous system herpes simplex virus infection is suspected in patients
      presenting with acute-onset seizures and lethargy. The potential neurologic
      sequelae from untreated herpes infection can prompt empirical acyclovir therapy,
      even in afebrile subjects. The objectives of this study were to determine the
      frequency of central nervous system herpes simplex virus infection in children
      presenting with afebrile seizures and to assess the need for empirical acyclovir
      therapy. Clinical and laboratory data of children with acute-onset afebrile
      seizures and children with central nervous system herpes simplex virus infection
      were compared. Polymerase chain reaction and viral cultures of the cerebrospinal
      fluid for herpes simplex virus infection were negative in all subjects with
      afebrile seizures; 32.7% of these subjects were empirically treated with
      acyclovir. In conclusion, central nervous system herpes simplex virus infection
      is uncommon in children presenting with afebrile seizures, and acyclovir therapy
      is rarely necessary in subjects with normal neurologic examination and
      cerebrospinal fluid analysis.

PMID- 21940691
TI  - Pallidal deep-brain stimulation associated with complete remission of self
      injurious behaviors in a patient with Lesch-Nyhan syndrome: a case report.
AB  - The purpose of this case report is to review the management of a boy with Lesch
      Nyhan syndrome with deep-brain stimulation who had remission of self-injurious
      behaviors as a result. This patient was treated with intrathecal baclofen and,
      later, with deep-brain stimulation to reduce hypertonia. Goals were to improve
      wheelchair positioning for school attendance and to reduce the use of restraints
      for comfort. Intrathecal baclofen was implanted twice and decreased the
      hypertonia, but both were explanted because of infection. Deep-brain stimulation
      was initiated 2.5 years ago, and since that time, comfort and function have
      improved and caregiver burden has decreased. Improvements in dystonia with deep
      brain stimulation have also occurred, and self-injurious behaviors have resolved.

PMID- 21940690
TI  - Long-term outcome in children with intractable epilepsy showing bilateral diffuse
      cortical glucose hypometabolism pattern on positron emission tomography.
AB  - The objective of this study is to determine the long-term outcome of children
      with intractable epilepsy who have diffuse cortical hypometabolism on 2-deoxy-2
      ((18)F)fluoro-D-glucose positron emission tomography (FDG-PET) scans. Seventeen
      children with intractable epilepsy showing bilateral, diffuse cortical
      hypometabolism on FDG-PET were followed up through telephone interview from 1
      year 4 months to 11 years 4 months (mean: 5 years 7 months +/- 2 years 1 month)
      after their PET scans. One child succumbed to Sanfilippo disease at age 20 years.
      Only 2 children were seizure free. Fifty percent had walking difficulties, 56.25%
      were not toilet trained, all had speech difficulties, 43.75% had behavioral
      problems, 37.5% had poor eye contact, 75% had socialization difficulties, and
      87.5% attended special schools. Three children were found to have genetic causes,
      including a 4-MB deletion of the mitochondrial genome, MECP2 duplication, and
      Lafora disease. In conclusion, the long-term outcome in this patient population
      is poor, and they tend to suffer from genetic/neurodegenerative diseases.

PMID- 21940692
TI  - Unusual case of relapsing and remitting rash with progressive motor sensory
      neuropathy and spinal cord atrophy.
AB  - The authors report a case of a 7-year-old girl with a progressive sensorimotor
      peripheral neuropathy with acute relapses associated with a desquamating purpuric
      rash, alopecia, and spinal cord atrophy. Distinctive features include systemic
      involvement with alopecia and rash, peripheral nervous system involvement with
      relapsing and remitting sensorimotor neuropathy, and central nervous system
      involvement with episodes of dystonic posturing and spinal cord atrophy.
      Extensive diagnostic evaluation for known causes of skin manifestations
      associated with peripheral neuropathy has failed to identify a cause for this
      patient's condition. The authors discuss the case as an approach to the
      differential diagnosis and to highlight unusual features of this yet to be
      identified clinical entity.

PMID- 21940693
TI  - Stimulus evaluation, event preparation, and motor action planning in young
      patients with mild spastic cerebral palsy: an event-related brain potential
      study.
AB  - The study investigated stimulus evaluation time, event preparation, and motor
      action planning of patients with mild spastic cerebral palsy and a peer control
      group in the age range of 9 to 18 years. To this end, participants were carrying
      out a stimulus recognition task. Findings indicated an overall slowness and
      inaccurate reaction time performance of the patient group. An event-related
      potential analysis revealed that the stimulus evaluation processing, indexed by
      the parietal P300, was intact in the group of patients. Also event preparation
      and action planning, indexed by respectively the frontal late contingent negative
      variation and the frontal P2, were intact in the group of patients. It was
      concluded that patients' motor slowness reflected poor motor execution processes.

PMID- 21940694
TI  - Is oral baclofen effective in neonatal hypertonia?
AB  - Cerebral palsy is often associated with spasticity. This study was designed to
      evaluate the effect of oral baclofen in hypertonic neonates. Retrospective chart
      review of patients treated with oral baclofen (identified by means of pharmacy
      records) during a 3-year period was undertaken. Data on muscle tone evaluated
      using the Modified Ashworth Scale scores were analyzed for effectiveness. Twenty
      nine infants had Modified Ashworth Scale scores before and during oral baclofen
      therapy. The study infants had a mean gestational age of 25.7 +/- 1.9 weeks.
      Baclofen was started at a postnatal age of 86.4 +/- 33.6 days. Comparison of
      Modified Ashworth Scale scores after initiation of therapy to prebaclofen scores
      demonstrated no significant decrease in muscle tone. Results of our study show
      that there is no overall decrease in tone during oral baclofen therapy in
      hypertonic preterm neonates.

PMID- 21940696
TI  - Congenital dysplastic microcephaly and hypoplasia of the brainstem and cerebellum
      with diffuse intracranial calcification.
AB  - Congenital microcephaly with intracranial calcification is a rare condition
      presented in heterogeneous diseases. Here, we report the case of a 1-year-old boy
      with severe congenital microcephaly and diffuse calcification. Neuroimaging
      studies showed a diffuse simplified gyral pattern; a very thin cortex;
      ventricular dilatation; very small basal ganglia, thalamus, and brainstem; and
      cerebellar hypoplasia with diffuse calcification. Clinical features of
      intrauterine infections, such as neonatal jaundice, hepatomegaly, and
      thrombocytopenia, were not found. Serological tests, cultures, and polymerase
      chain reaction analysis were negative for viral infections. The etiology of
      pseudo-toxoplasmosis, rubella, cytomegalovirus, and herpes simplex syndrome is
      still unknown. This study describes the most severe form of pseudo-toxoplasmosis,
      rubella, cytomegalovirus, and herpes simplex syndrome reported to date, with the
      patient showing microcephaly and calcification or band-like intracranial
      calcification with simplified gyration and polymirogyria.

PMID- 21940695
TI  - Drooling: are botulinum toxin injections into the major salivary glands a good
      treatment option?
AB  - There are several treatment options available for drooling; botulinum toxin
      injections into the major salivary glands are one. There is no consensus as to
      how many and which glands should be injected. A research project on this topic
      was terminated because of adverse effects. Individual results and the adverse
      effects are described and discussed in this article. Six individuals with
      cerebral palsy were randomly allocated to 2 treatment groups, with five
      individuals receiving ultrasound-guided injections to parotid and submandibular
      glands and one receiving injections to the submandibular glands only. Reduction
      of observed drooling was registered in 3, while 4 patients reported subjective
      improvement (Visual Analog Scale). Two participants reported adverse effects,
      including dysphagia, dysarthria, and increased salivary viscosity. Injections
      with botulinum toxin can be a useful treatment option but there is a risk of
      adverse effects. Multidisciplinary evaluation and informed discussions with
      patients/caregivers are important factors in the decision-making process.

PMID- 21940697
TI  - An unusual presentation of juvenile Alexander disease.
AB  - Alexander disease is a rare leukodystrophy that most often presents in infancy
      but also includes neonatal, juvenile, and adult variants. Juvenile Alexander
      disease presents primarily with bulbar symptoms between 2 and 12 years of age.
      The diagnosis is often suggested by the clinical course and brain magnetic
      resonance image pattern and then confirmed by the presence of a mutation in the
      glial fibrillary acidic protein gene. A young girl presented with globus
      sensation and magnetic resonance imaging of the brain revealed abnormalities
      mainly involving white matter tracts of the medulla oblongata and cerebellum. The
      presence of a mutation in the glial fibrillary acidic protein gene confirmed the
      diagnosis of juvenile Alexander disease. A high index of clinical suspicion is
      necessary for the diagnosis of late-onset presentations of Alexander disease.

PMID- 21940698
TI  - Cerebellar gliomatosis in a toddler: case report of a challenging condition and
      review of the literature.
AB  - Gliomatosis confined to the cerebellum is most unusual. We report such a case in
      a 20-month-old male who presented with unsteadiness. Magnetic resonance imaging
      revealed a diffuse area of abnormal signal intensity within both cerebellar
      hemispheres, which did not enhance after contrast administration. The patient
      underwent a biopsy, which revealed a diffuse glioma infiltrating the cerebellum.
      Overall, the tumor cells had oligodendroglioma-like features and exhibited only
      focal vimentin immunoreactivity. They were negative for glial fibrillary acidic
      protein, synaptophysin, betaIII-tubulin, and neurofilament protein.
      Immunofluorescence, performed on primary biopsy explants maintained in cell
      culture without exposure to growth factors or differentiation-promoting agents,
      revealed widespread nestin immunoreactivity and immunolabeling of occasional
      cells with antibodies to platelet-derived growth factor-alpha and O1/O4, markers
      of oligodendrocyte precursor-cells and immature oligodendrocytes, respectively.
      Fluorescent in situ hybridization performed on explants, touch preparations, and
      paraffin sections failed to reveal loss of heterozygosity for either 1p36 or
      19q13. The patient was treated with temozolomide and remains stable, albeit with
      residual quiescent tumor, more than 3 years after surgery. This report calls
      attention to an unusual presentation of gliomatosis confined to the cerebellum of
      a toddler and addresses salient aspects of clinical and radiological differential
      diagnosis, as well as therapeutic challenges encountered.

PMID- 21940699
TI  - Clinical associations of occipital intermittent rhythmic delta activity.
AB  - Association of occipital intermittent rhythmic delta activity with absence
      seizures has been well documented in the published literature. Two recent studies
      have also described an association with focal seizures. After obtaining approval
      from our Institutional Review Board, all electroencephalograms with occipital
      intermittent rhythmic delta activity at our institution between July 1, 2006 and
      December 31, 2009 were identified. Charts of these patients were reviewed to
      collect clinical data. A matched comparison group was assembled. Thirty-one of
      the patients who met criteria had evaluable clinical data. Fifteen had
      generalized seizures (9 absence; 2 tonic-clonic; 3 absence and tonic-clonic; 1
      absence, tonic-clonic, myoclonic, and atonic). Eleven had focal seizures. One had
      both generalized tonic-clonic and focal seizures. Events in 1 were nonepileptic
      in nature. Documentation was inadequate for seizure classification in 3. There
      was a statistically significant difference between the study and comparison
      groups for absence seizures, but not for focal seizures.

PMID- 21940700
TI  - Validation of the Expanded Hammersmith Functional Motor Scale in spinal muscular
      atrophy type II and III.
AB  - The relationships between the Expanded Hammersmith Functional Motor Scale (HFMSE)
      and genotype and motor and respiratory outcomes were examined in patients with
      spinal muscular atrophy types II and III (n = 70). The correlation between the
      HFMSE and Gross Motor Function Measure was r = 0.98. Correlations between HFMSE
      and forced vital capacity (percentage of predicted normal) (n = 56) and a
      functional rating (n = 57) were r = 0.87 and r = 0.92, respectively. Correlations
      with strength were as follows: knee extension, r = 0.74 (n = 60); elbow flexion,
      r = 0.77 (n = 61); and knee flexion, r = 0.74 (n = 58). The HFMSE differentiated
      patients by SMN2 copy number (P = .0007); bi-level positive airway pressure use,
      <8 versus >=8 hours/day (P < .0001); ambulatory status (P < .0001); and spinal
      muscular atrophy type (P < .0001). The HFMSE demonstrates significant
      associations with established measures of function, strength, and genotype, and
      discriminates patients based on function, diagnostic category, and bi-level
      positive airway pressure need. Time of administration averaged 12 minutes. The
      HFMSE is a valid, time-efficient outcome measure for clinical trials in spinal
      muscular atrophy types II and III.

PMID- 21940702
TI  - Altered neuronal activity patterns in the visual cortex of the adult rat after
      partial optic nerve crush--a single-cell resolution metabolic mapping study.
AB  - Thallium autometallography (TIAMG) is a novel method for high-resolution mapping
      of neuronal activity. With this method, we found that a general depression of
      neuronal activity occurs in response to optic nerve crush (ONC) within the first
      2 weeks postinjury in the contralateral dorsal lateral geniculate nucleus (dLGN)
      as well as in the contralateral primary visual cortex (V1). Interestingly, the
      neuronal activity recovered thereafter in both brain regions and reached a
      plateau in the tenth week postinjury in layers IV and V of V1, monocular area
      (V1m). Several clusters of highly active neurons in V1m were found 6 weeks after
      ONC in layers IV and V on the side contralateral to the lesion. We reasoned that
      these clusters appeared due to a reorganization of the corticocolliucular
      projections. Employing a combination of biotinylated dextran amine retrograde
      tract tracing from the superior colliculus (SC) with TIAMG in the same animal, we
      indeed found that the clusters of neurons with high Tl(+) uptake in V1m are
      spatially in register with those neuronal subpopulations that project to the SC.
      These data suggest that extensive reorganization plasticity exists in the adult
      rat visual cortex following ONC.

PMID- 21940703
TI  - Normative development of white matter tracts: similarities and differences in
      relation to age, gender, and intelligence.
AB  - The white matter of the brain undergoes a range of structural changes throughout
      development; from conception to birth, in infancy, and onwards through childhood
      and adolescence. Several studies have used diffusion magnetic resonance imaging
      (dMRI) to investigate these changes, but a consensus has not yet emerged on which
      white matter tracts undergo changes in the later stages of development or what
      the most important driving factors are behind these changes. In this study of
      typically developing 8- to 16-year-old children, we use a comprehensive data
      driven approach based on principal components analysis to identify effects of
      age, gender, and brain volume on dMRI parameters, as well as their relative
      importance. We also show that secondary components of these parameters predict
      full-scale IQ, independently of the age- and gender-related effects. This
      overarching assessment of the common factors and gender differences in normal
      white matter tract development will help to advance understanding of this process
      in late childhood and adolescence.

PMID- 21940701
TI  - Androgen influence on prefrontal dopamine systems in adult male rats:
      localization of cognate intracellular receptors in medial prefrontal projections
      to the ventral tegmental area and effects of gonadectomy and hormone replacement
      on glutamate-stimulated extracellular dopamine level.
AB  - Although androgens are known to modulate dopamine (DA) systems and DA-dependent
      behaviors of the male prefrontal cortex (PFC), how this occurs remains unclear.
      Because relatively few ventral tegmental area (VTA) mesoprefrontal DA neurons
      contain intracellular androgen receptors (ARs), studies presented here combined
      retrograde tracing and immunolabeling for AR in male rats to determine whether
      projections afferent to the VTA might be more AR enriched. Results revealed PFC
      to-VTA projections to be substantially AR enriched. Because these projections
      modulate VTA DA cell firing and PFC DA levels, influence over this pathway could
      be means whereby androgens modulate PFC DA. To assess the hormone sensitivity of
      glutamate stimulation of PFC DA tone, additional studies utilized
      microdialysis/reverse dialysis application of alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid and N-methyl-D-aspartate receptor subtype-selective
      antagonists which act locally within the PFC and tegmentally via inhibition or
      disinhibition of PFC-to-VTA afferents to modulate intracortical DA levels. Here,
      we compared the effects of these drug challenges in control, gonadectomized, and
      gonadectomized rats given testosterone or estradiol. This revealed complex
      effects of gonadectomy on antagonist-stimulated PFC DA levels that together with
      the anatomical data above suggest that androgen stimulation of PFC DA systems
      does engage glutamatergic circuitry and perhaps that of the AR-enriched
      glutamatergic projections from PFC-to-VTA specifically.

PMID- 21940704
TI  - Performance Dip in motor response induced by task-irrelevant weaker coherent
      visual motion signals.
AB  - The Performance Dip is a newly characterized behavioral phenomenon, where,
      paradoxically, a weaker task-irrelevant visual stimulus causes larger
      disturbances on the accuracy of a main letter identification task than a stronger
      stimulus does. Understanding mechanisms of the Performance Dip may provide
      insight into unconsciousness behavior. Here, we investigated the generalization
      of the Performance Dip. Specifically, we tested whether the Performance Dip
      occurs in a motion-related Simon task, and if so, whether the Performance Dip
      involves the same brain region, that is, the dorsolateral prefrontal cortex
      (DLPFC), previously implicated in the Performance Dip, or the supplementary motor
      area (SMA) and pre-SMA, implicated in a motion-related Simon Task. Subjects made
      manual directional responses according to the color of stochastic moving dots
      while ignoring the global direction of moving dots, which could be either
      congruent or incongruent to the response appropriate to the main task. We found
      that weak incongruent task-irrelevant stimuli caused a Performance Dip, in which
      the SMA and pre-SMA, rather than DLPFC, played critical roles. Our results
      suggest a possible common brain mechanism across different neural circuits, in
      which weak, but not strong, task-irrelevant information is free from inhibition
      and intrudes into neural circuits relevant to the main task.

PMID- 21940705
TI  - Transcriptional mechanisms of EphA7 gene expression in the developing cerebral
      cortex.
AB  - The patterning of cortical areas is controlled by a combination of intrinsic
      factors that are expressed in the cortex and external signals such as inputs from
      the thalamus. EphA7 is a guidance receptor that is involved in key aspects of
      cortical development and is expressed in gradients within developing cortical
      areas. Here, we identified a regulatory element of the EphA7 promoter, named pA7,
      that can recapitulate salient features of the pattern of expression of EphA7,
      including cortical gradients. Using a pA7-Green fluorescent Protein (GFP) mouse
      reporter line, we isolated cortical neuron populations displaying different
      levels of EphA7/GFP expression. Transcriptome analysis of these populations
      enabled to identify many differentially expressed genes, including 26
      transcription factors with putative binding sites in the pA7 element. Among
      these, Pbx1 was found to bind directly to the EphA7 promoter in the developing
      cortex. All genes validated further were confirmed to be expressed differentially
      in the developing cortex, similarly to EphA7. Their expression was unchanged in
      mutant mice defective for thalamocortical projections, indicating a
      transcriptional control largely intrinsic to the cortex. Our study identifies a
      novel repertoire of cortical neuron genes that may act upstream of, or together
      with EphA7, to control the patterning of cortical areas.

PMID- 21940706
TI  - Colocalization of alpha-actinin and synaptopodin in the pyramidal cell axon
      initial segment.
AB  - The cisternal organelle that resides in the axon initial segment (AIS) of
      neocortical and hippocampal pyramidal cells is thought to be involved in
      regulating the Ca(2+) available to maintain AIS scaffolding proteins, thereby
      preserving normal AIS structure and function. Through immunocytochemistry and
      correlative light and electron microscopy, we show here that the actin-binding
      protein alpha-actinin is present in the typical cistenal organelle of rodent
      pyramidal neurons as well as in a large structure in the AIS of a subpopulation
      of layer V pyramidal cells that we have called the "giant saccular organelle."
      Indeed, this localization of alpha-actinin in the AIS is dependent on the
      integrity of the actin cytoskeleton. Moreover, in the cisternal organelle of
      cultured hippocampal neurons, alpha-actinin colocalizes extensively with
      synaptopodin, a protein that interacts with both actin and alpha-actinin, and
      they appear concomitantly during the development of these neurons. Together,
      these results indicate that alpha-actinin and the actin cytoskeleton are
      important components of the cisternal organelle that are probably required to
      stabilize the AIS.

PMID- 21940707
TI  - The large-scale organization of "visual" streams emerges without visual
      experience.
AB  - A key question in sensory perception is the role of experience in shaping the
      functional architecture of the sensory neural systems. Here we studied dependence
      on visual experience in shaping the most fundamental division of labor in vision,
      namely between the ventral "what" and the dorsal "where and how" processing
      streams. We scanned 11 fully congenitally blind (CB) and 9 sighted individuals
      performing location versus form identification tasks following brief training on
      a sensory substitution device used for artificial vision. We show that the
      dorsal/ventral visual pathway division of labor can be revealed in the adult CB
      when perceiving sounds that convey the relevant visual information. This suggests
      that the most important large-scale organization of the visual system into the 2
      streams can develop even without any visual experience and can be attributed at
      least partially to innately determined constraints and later to cross-modal
      plasticity. These results support the view that the brain is organized into task
      specific but sensory modality-independent operators.

PMID- 21940708
TI  - Role of Rho GTPases in human trophoblast migration induced by IGFBP1.
AB  - Insulin-like growth factor binding protein 1 (IGFBP1), the main secretory product
      of the decidualized endometrium of a pregnant woman, has previously been shown to
      interact with the alpha(5)beta(1) integrin of extravillous trophoblast (EVT) cell
      surface to stimulate its migration in an IGF-independent manner. This migration
      stimulation has also been shown to require activation of extracellular signal
      regulated kinases 1 and 2 (ERK1/2; mitogen-activated protein kinase [MAPK] 3/1])
      and focal adhesion kinase. The present study examined the roles of Rho GTPases
      RHOA, RHOC, RAC1, and CDC42 as well as RHO kinases ROCK1 and ROCK2 in IGFBP1
      mediated migration of an immortalized EVT cell line HTR-8/SVneo. A nonselective
      RHO kinase inhibitor, Y27632, as well as siRNAs selective for ROCK1 and ROCK2
      decreased the migration of these cells in a Transwell migration assay, and this
      inhibition could not be restored by IGFBP1. Clostridium difficile toxin B, which
      inhibits all the Rho GTPases, RAC inhibitor NSC23766, RAC1 siRNA, and CDC42
      siRNA, decreased their basal migration, but none of these inhibitions except
      CDC42 siRNA-induced inhibition could be restored by IGFBP1. Clostridium botulinum
      C3 exoenzyme that inhibits RHOA, RHOB, and RHOC inhibited basal migration but not
      IGFBP1-induced migration. IGFBP1-induced activation of ERK1/2 (MAPK3/1), which
      did not require RHO proteins, might function as an alternate pathway for RHO
      action. However, selective siRNA-mediated downregulation of RHOA inhibited basal,
      but not IGFBP1-mediated, migration, whereas that of RHOC inhibited both basal and
      IGFBP1-mediated migration of these EVT cells. Therefore, RHO kinase, RHOC, and
      RAC1 are essential, but RHOA and CDC42 are not essential, for IGFBP1-induced EVT
      migration.

PMID- 21940709
TI  - Swine leukocyte antigen-DQ expression and its regulation by interferon-gamma at
      the maternal-fetal interface in pigs.
AB  - Successful pregnancy requires an appropriate intrauterine immune response to the
      conceptus, which is a semiallograft within the uterus. We reported that swine
      leukocyte antigen-DQA (SLA-DQA), a major histocompatibility complex (MHC) class
      II gene, is expressed in the uterine endometrium at the time of conceptus
      implantation in pigs. Because MHC molecules play critical roles in the immune
      system, SLA-DQ was hypothesized to be involved in immune regulation during
      pregnancy. Therefore, we examined expression of SLA-DQ in uterine endometrial
      tissues obtained during the estrous cycle and pregnancy. SLA-DQA and SLA-DQB
      mRNAs were detected as 1.3-kb and 1.2-kb bands, respectively. Real-time RT-PCR
      analysis indicated that SLA-DQA and SLA-DQB mRNA expression was affected by day
      and pregnancy status, with the highest expression on Day 15 of pregnancy. SLA-DQ
      was localized primarily to subepithelial stromal cells and endothelial cells of
      the uterus. Using endometrial explant cultures from Day 12 of the estrous cycle,
      we determined that expression of SLA-DQA and SLA-DQB mRNAs increased in response
      to interferon-gamma (IFNG), which is produced by pig conceptus trophectoderm
      between Days 14 and 18 of pregnancy. The abundance of SLA-DQ protein was less in
      endometria from gilts with conceptuses resulting from somatic cell nuclear
      transfer compared with endometria from gilts with conceptuses resulting from
      natural mating. These results support our hypothesis that SLA-DQ is expressed in
      response to IFNG from the conceptus, and likely regulates immune response at the
      maternal-fetal interface to support the maintenance of pregnancy in pigs.

PMID- 21940710
TI  - Case studies of minimizing nonspecific inhibitors in HTS campaigns that use assay
      ready plates.
AB  - Identifying chemical lead matter by high-throughput screening (HTS) has been a
      common practice in early stage drug discovery. Evolution of small-molecule
      library composition to include more drug-like molecules with desirable physical
      chemical properties combined with improving assay technologies has vastly
      enhanced the capability of HTS. However, HTS campaigns can still be plagued by
      false positives arising from nonspecific inhibitors. The generation of assay
      ready plates has permitted an incremental advancement to the speed and efficiency
      of HTS but has the potential to enhance the occurrence of nonspecific inhibitors.
      A subtle change in the order of reagent addition to the assay-ready plates can
      greatly alleviate false-positive inhibition. Our case studies with six different
      kinase and protease targets reveal that this type of inhibition affects targets
      regardless of enzyme class and is unpredictable based on protein construct or
      inhibitor chemical scaffold. These case studies support a model where a diversity
      set of compounds should be tested first for hit rates as a function of order of
      addition, carrier protein, and relevant mechanistic studies prior to launch of
      the HTS campaign.

PMID- 21940711
TI  - High-throughput screening of potassium-competitive acid blockers.
AB  - H(+),K(+)-ATPase is a key enzyme in the process of gastric acid secretion, and
      proton pump inhibitors (PPIs) have been accepted as one of the most effective
      treatments for peptic ulcer and gastroesophageal reflux disease. To discover a
      novel class of PPIs, the authors screened a low-molecular-weight compound library
      and identified two prospective acid blockers that were pyrrole derivatives. Both
      compounds inhibited H(+),K(+)-ATPase in a reversible and potassium-competitive
      manner. These compounds led to the development of TAK-438 (1-[5-(2-fluorophenyl)
      1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine monofumarate), which
      is currently undergoing clinical trials as a novel potassium-competitive acid
      blocker for the treatment of acid-related diseases.

PMID- 21940712
TI  - Development of a colorimetric assay and kinetic analysis for Mycobacterium
      tuberculosis D-glucose-1-phosphate thymidylyltransferase.
AB  - dTDP-L-rhamnose as a sugar donor provides L-rhamnosyl residue in the synthesis of
      disaccharide linker (D-N-acetylglucosamine-L-rhamnose), the key structure of the
      Mycobacterium tuberculosis cell wall. Four enzymes are involved in the formation
      of dTDP-L-rhamnose and D-glucose-1-phosphate thymidylyltransferase (RmlA)
      catalyzes the first step of D-glucose-1-phosphate and dTTP to dTDP-D-glucose and
      PPi. The previous studies on RmlA essentiality proved RmlA as a potential target
      for antituberculosis drugs. However, there has not been a suitable assay for RmlA
      to screen inhibitors currently. In this study, the authors reported a microtiter
      plate-based colorimetric assay for RmlA enzyme activity. Using this assay, the
      kinetic properties of M. tuberculosis RmlA including initial velocity, optimal
      temperature, optimal pH, the effect of Mg(2+), and kinetic parameters were
      determined. The establishment of the accurate and rapid colorimetric assay and
      kinetic analysis of M. tuberculosis RmlA will facilitate high-throughput
      screening of RmlA inhibitors.

PMID- 21940713
TI  - A substrate-independent TR-FRET histone deacetylase inhibitor assay.
AB  - Developing molecularly targeted therapeutics with minimal off-target effects is
      facilitated by an understanding of compound selectivity. However, for HDAC
      inhibitors, a clear understanding of specificity has been challenging. In
      particular, it has been suggested that use of nonspecific substrates and the
      presence of multiple HDAC activities in enzyme preparations may complicate
      interpretation of inhibitor experiments. To overcome these and other potential
      limitations of activity-based HDAC assays, the authors have developed an assay
      format based on measurement of the binding affinity of inhibitors rather than
      measurement of enzyme activity. One advantage of this format is that it does not
      require use of a substrate and thus ameliorates concerns about lack of
      specificity of existing substrates. This assay is based on an Alexa Fluor(r) 647
      labeled HDAC inhibitor or "tracer," which binds with a high affinity to Class I
      and Class IIb HDACs. Unlike activity assays, which can be affected by the
      presence of residual untagged endogenous HDACs from the host expression system,
      the signal in this format is dependent on the presence of an epitope tag on the
      specific HDAC of interest. The authors demonstrate the utility of this method by
      determining the potencies of commonly used inhibitors for six human HDACs.

PMID- 21940714
TI  - Development of homogeneous nonradioactive methyltransferase and demethylase
      assays targeting histone H3 lysine 4.
AB  - Histone posttranslational modifications are among the epigenetic mechanisms that
      modulate chromatin structure and gene transcription. Histone methylation and
      demethylation are dynamic processes controlled respectively by histone
      methyltransferases (HMTs) and demethylases (HDMs). Several HMTs and HDMs have
      been implicated in cancer, inflammation, and diabetes, making them attractive
      targets for drug therapy. Hence, the discovery of small-molecule modulators for
      these two enzyme classes has drawn significant attention from the pharmaceutical
      industry. Herein, the authors describe the development and optimization of
      homogeneous LANCE Ultra and AlphaLISA antibody-based assays for measuring the
      catalytic activity of two epigenetic enzymes acting on lysine 4 of histone H3:
      SET7/9 methyltransferase and LSD1 demethylase. Both the SET7/9 and LSD1 assays
      were designed as signal-increase assays using biotinylated peptides derived from
      the N-terminus of histone H3. In addition, the SET7/9 assay was demonstrated
      using full-length histone H3 protein as substrate in the AlphaLISA format.
      Optimized assays in 384-well plates are robust (Z' factors >=0.7) and sensitive,
      requiring only nanomolar concentrations of enzyme and substrate. All assays
      allowed profiling of known SET7/9 and LSD1 inhibitors. The results demonstrate
      that the optimized LANCE Ultra and AlphaLISA assay formats provide a relevant
      biochemical screening approach toward the identification of small-molecule
      inhibitors of HMTs and HDMs that could lead to novel epigenetic therapies.

PMID- 21940715
TI  - Structural alerts for predicting clastogenic activity of pro-oxidant flavonoid
      compounds: quantitative structure-activity relationship study.
AB  - Flavonoids have been reported to exert multiple biological effects that include
      acting as pro-oxidants at very high doses. The authors determined a structural
      alert to identify the clastogenic activity of a series of flavonoids with pro
      oxidant activity. The methodology was based on a quantitative structure-activity
      relationship (QSAR) study. Specifically, the authors developed a virtual
      screening method for a clastogenic model using the topological substructural
      molecular design (TOPS-MODE) approach. It represents a useful platform for the
      automatic generation of structural alerts, based on the calculation of spectral
      moments of molecular bond matrices appropriately weighted, taking into account
      the hydrophobic, electronic, and steric molecular features. Therefore, it was
      possible to establish the structural criteria for maximal clastogenicity of pro
      oxidant flavonoids: the presence of a 3-hydroxyl group and a 4-carbonyl group in
      ring C, the maximal number of hydroxyl groups in ring B, the presence of methoxyl
      and phenyl groups, the absence of a 2,3-double bond in ring C, and the presence
      of 5,7 hydroxyl groups in ring A. The presented clastogenic model may be useful
      for screening new pro-oxidant compounds. This alert could help in the design of
      new and efficient flavonoids, which could be used as bioactive compounds in
      nutraceuticals and functional food.

PMID- 21940716
TI  - Exposure-clinical response analysis of paricalcitol in patients with chronic
      kidney disease (stage 5) on hemodialysis or peritoneal dialysis.
AB  - Paricalcitol injection and capsules are approved for the prevention and treatment
      of secondary hyperparathyroidism. Exposure-response analyses were performed to
      describe paricalcitol pharmacokinetics and the relationship to clinical responses
      (intact parathyroid hormone [iPTH], serum calcium, and phosphorus) following
      administration of paricalcitol capsules or injection to patients with chronic
      kidney disease (stage 5). Paricalcitol pharmacokinetics were similar following
      intravenous and oral administration with mean oral clearance of 1.75 L/h and
      bioavailability of 75.1%. Exposure-clinical response was best described by an
      indirect effects model where serum iPTH, calcium, and phosphorus production rates
      were directly affected by paricalcitol. Significant covariates in the response
      model included screening iPTH, calcium, and phosphorus on their corresponding
      synthesis rates; age on iPTH EC(50); and bone-specific alkaline phosphatase on
      calcium EC(50) (CRIT). This exposure-response model was used in extensive
      clinical trial simulations to assess alternative dose regimens for CKD stage 5
      patients.

PMID- 21940717
TI  - Genetic analysis reveals a complex regulatory network modulating CBF gene
      expression and Arabidopsis response to abiotic stress.
AB  - Arabidopsis CBF genes (CBF1-CBF3) encode transcription factors having a major
      role in cold acclimation, the adaptive process whereby certain plants increase
      their freezing tolerance in response to low non-freezing temperatures. Under
      these conditions, the CBF genes are induced and their corresponding proteins
      stimulate the expression of target genes configuring low-temperature
      transcriptome and conditioning Arabidopsis freezing tolerance. CBF2 seems to be
      the most determinant of the CBFs since it also regulates CBF1 and CBF3
      expression. Despite the relevance of CBF genes in cold acclimation, little is
      known about the molecular components that control their expression. To uncover
      factors acting upstream of CBF2, mutagenized Arabidopsis containing the
      luciferase reporter gene under the control of the CBF2 promoter were screened for
      plants with de-regulated CBF2 expression. Here, the identification and
      characterization of five of these mutants, named acex (altered CBF2 expression),
      is presented. Three mutants show increased levels of cold-induced CBF2
      transcripts compared with wild-type plants, the other two exhibiting reduced
      levels. Some mutants are also affected in cold induction of CBF1 and CBF3.
      Furthermore, the mutants characterized display unique phenotypes for tolerance to
      abiotic stresses, including freezing, dehydration, and high salt. These results
      demonstrate that cold induction of CBF2 is subjected to both positive and
      negative regulation through different signal transduction pathways, some of them
      also mediating the expression of other CBF genes as well as Arabidopsis responses
      to abiotic stresses.

PMID- 21940718
TI  - Calcium-sensing receptor regulates stomatal closure through hydrogen peroxide and
      nitric oxide in response to extracellular calcium in Arabidopsis.
AB  - The Arabidopsis calcium-sensing receptor CAS is a crucial regulator of
      extracellular calcium-induced stomatal closure. Free cytosolic Ca(2+) (Ca(2+)(i))
      increases in response to a high extracellular calcium (Ca(2+)(o)) level through a
      CAS signalling pathway and finally leads to stomatal closure. Multidisciplinary
      approaches including histochemical, pharmacological, fluorescent,
      electrochemical, and molecular biological methods were used to discuss the
      relationship of hydrogen peroxide (H(2)O(2)) and nitric oxide (NO) signalling in
      the CAS signalling pathway in guard cells in response to Ca(2+)(o). Here it is
      shown that Ca(2+)(o) could induce H(2)O(2) and NO production from guard cells but
      only H(2)O(2) from chloroplasts, leading to stomatal closure. In addition, the
      CASas mutant, the atrbohD/F double mutant, and the Atnoa1 mutant were all
      insensitive to Ca(2+)(o)-stimulated stomatal closure, as well as H(2)O(2) and NO
      elevation in the case of CASas. Furthermore, it was found that the antioxidant
      system might function as a mediator in Ca(2+)(o) and H(2)O(2) signalling in guard
      cells. The results suggest a hypothetical model whereby Ca(2+)(o) induces
      H(2)O(2) and NO accumulation in guard cells through the CAS signalling pathway,
      which further triggers Ca(2+)(i) transients and finally stomatal closure. The
      possible cross-talk of Ca(2+)(o) and abscisic acid signalling as well as the
      antioxidant system are discussed.

PMID- 21940719
TI  - Role of ARABIDOPSIS A-FIFTEEN in regulating leaf senescence involves response to
      reactive oxygen species and is dependent on ETHYLENE INSENSITIVE2.
AB  - Leaf senescence is a highly regulated developmental process that is coordinated
      by several factors. Many senescence-associated genes (SAGs) have been identified,
      but their roles during senescence remain unclear. A sweet potato (Ipomoea
      batatas) SAG, named SPA15, whose function was unknown, was identified previously.
      To understand the role of SPA15 in leaf senescence further, the orthologue of
      SPA15 in Arabidopsis thaliana was identified and characterized, and it was named
      ARABIDOPSIS A-FIFTEEN (AAF). AAF was expressed in early senescent leaves and in
      tissues with highly proliferative activities. AAF was localized to the
      chloroplasts by transient expression in Arabidopsis mesophyll protoplasts.
      Overexpression of AAF (AAF-OX) in Arabidopsis promoted, but the T-DNA insertion
      mutant (aaf-KO), delayed age-dependent leaf senescence. Furthermore, stress
      induced leaf senescence caused by continuous darkness was enhanced in AAF-OX but
      suppressed in aaf-KO. Transcriptome analysis of expression profiles revealed up
      regulated genes related to pathogen defence, senescence, and oxidative stress in
      3-week-old AAF-OX plants. Indeed, elevated levels of reactive oxygen species
      (ROS) and enhanced sensitivity to oxidative and dark stress were apparent in AAF
      OX but reduced in aaf-KO. ETHYLENE INSENSITIVE2 (EIN2) was required for the dark-
      and ROS-induced senescence phenotypes in AAF-OX and the induction of AAF
      expression by treatment with the immediate precursor of ethylene, 1
      aminocyclopropane-1-carboxylic acid. The results indicate the functional role of
      AAF is an involvement in redox homeostasis to regulate leaf senescence mediated
      by age and stress factors during Arabidopsis development.

PMID- 21940720
TI  - Functional characterization of barley betaglucanless mutants demonstrates a
      unique role for CslF6 in (1,3;1,4)-beta-D-glucan biosynthesis.
AB  - (1,3;1,4)-beta-D-glucans (mixed-linkage glucans) are found in tissues of members
      of the Poaceae (grasses), and are particularly high in barley (Hordeum vulgare)
      grains. The present study describes the isolation of three independent (1,3;1,4)
      beta-D-glucanless (betaglucanless; bgl) mutants of barley which completely lack
      (1,3;1,4)-beta-D-glucan in all the tissues tested. The bgl phenotype cosegregates
      with the cellulose synthase like HvCslF6 gene on chromosome arm 7HL. Each of the
      bgl mutants has a single nucleotide substitution in the coding region of the
      HvCslF6 gene resulting in a change of a highly conserved amino acid residue of
      the HvCslF6 protein. Microsomal membranes isolated from developing endosperm of
      the bgl mutants lack detectable (1,3;1,4)-beta-D-glucan synthase activity
      indicating that the HvCslF6 protein is inactive. This was confirmed by transient
      expression of the HvCslF6 cDNAs in Nicotiana benthamiana leaves. The wild-type
      HvCslF6 gene directed the synthesis of high levels of (1,3;1,4)-beta-D-glucans,
      whereas the mutant HvCslF6 proteins completely lack the ability to synthesize
      (1,3;1,4)-beta-D-glucans. The fine structure of the (1,3;1,4)-beta-D-glucan
      produced in the tobacco leaf was also very different from that found in cereals
      having an extremely low DP3/DP4 ratio. These results demonstrate that, among the
      seven CslF and one CslH genes present in the barley genome, HvCslF6 has a unique
      role and is the key determinant controlling the biosynthesis of (1,3;1,4)-beta-D
      glucans. Natural allelic variation in the HvCslF6 gene was found predominantly
      within introns among 29 barley accessions studied. Genetic manipulation of the
      HvCslF6 gene could enable control of (1,3;1,4)-beta-D-glucans in accordance with
      the purposes of use.

PMID- 21940721
TI  - Mesenteric fat as a source of C reactive protein and as a target for bacterial
      translocation in Crohn's disease.
AB  - OBJECTIVE: Mesenteric fat hyperplasia is a hallmark of Crohn's disease (CD), and
      C reactive protein (CRP) is correlated with disease activity. The authors
      investigated whether mesenteric adipocytes may be a source of CRP in CD and
      whether inflammatory and bacterial triggers may stimulate its production by
      adipocytes. DESIGN: CRP expression in the mesenteric and subcutaneous fats of
      patients with CD and the correlation between CRP plasma concentrations and
      mesenteric messenger RNA (mRNA) levels were assessed. The impact of inflammatory
      and bacterial challenges on CRP synthesis was tested using an adipocyte cell
      line. Bacterial translocation to mesenteric fat was studied in experimental
      models of colitis and ileitis and in patients with CD. RESULTS: CRP expression
      was increased in the mesenteric fat of patients with CD, with mRNA levels being
      80 +/- 40 (p<0.05) and 140 +/- 65 (p=0.04) times higher than in the mesenteric
      fat of patients with ulcerative colitis and in the subcutaneous fat of the same
      CD subjects, respectively, and correlated with plasma levels. Escherichia coli
      (1230 +/- 175-fold, p<0.01), lipopolysaccharide (26 +/- 0.5-fold, p<0.01), tumour
      necrosis factor alpha (15 +/- 0.3-fold, p<0.01) and interleukin-6 (10 +/- 0.7
      fold, p<0.05) increased CRP mRNA levels in adipocyte 3T3-L1 cells. Bacterial
      translocation to mesenteric fat occurred in 13% and 27% of healthy and CD
      subjects, respectively, and was increased in experimental colitis and ileitis.
      Human mesenteric adipocytes constitutively expressed mRNA for TLR2, TLR4, NOD1
      and NOD2. CONCLUSION: Mesenteric fat is an important source of CRP in CD. CRP
      production by mesenteric adipocytes may be triggered by local inflammation and
      bacterial translocation to mesenteric fat, providing a mechanism whereby
      mesenteric fat hyperplasia may contribute to inflammatory response in CD.

PMID- 21940722
TI  - Aberrant intestinal stem cell lineage dynamics in Peutz-Jeghers syndrome and
      familial adenomatous polyposis consistent with protracted clonal evolution in the
      crypt.
AB  - OBJECTIVE: Genetic predisposition to cancer in Peutz-Jeghers syndrome (PJS) and
      the role of germline serine-threonine kinase (LKB1) mutations are poorly
      understood. The authors studied the effect of germline LKB1 mutations on
      intestinal stem cell dynamics in unaffected flat PJS mucosa. Recent research has
      documented that the intestinal crypt houses multiple equipotent stem cell
      lineages. Lineages continuously compete through random drifts, while somatically
      inherited methylation patterns record clonal diversity. DESIGN: To study the
      effect of germline LKB1 mutations on clonal expansion, the authors performed
      quantitative analyses of cardiac-specific homeobox methylation pattern diversity
      in crypts isolated from unaffected colonic mucosa obtained from archival PJS
      patient material. The authors compared methylation density and methylation
      pattern diversity in patients with PJS to those in patients with familial
      adenomatous polyposis and age-matched controls. RESULTS: The percentage of total
      methylation is comparable between groups, but the number of unique methylation
      patterns is significantly increased for patients with familial adenomatous
      polyposis and patients with PJS compared to control subjects. CONCLUSIONS:
      Monoallelic LKB1 loss is not silent and provokes a protracted clonal evolution in
      the crypt. The increased methylation pattern diversity observed in unaffected PJS
      mucosa predicts that premalignant lesions will arise at an accelerated pace
      compared to the general population.

PMID- 21940723
TI  - Colonoscopy quality measures: experience from the NHS Bowel Cancer Screening
      Programme.
AB  - OBJECTIVES: Colonoscopy is central to colorectal cancer (CRC) screening. Success
      of CRC screening is dependent on colonoscopy quality. The NHS Bowel Cancer
      Screening Programme (BCSP) offers biennial faecal occult blood (FOB) testing to
      60-74 year olds and colonoscopy to those with positive FOB tests. All
      colonoscopists in the screening programme are required to meet predetermined
      standards before starting screening and are subject to ongoing quality assurance.
      In this study, the authors examine the quality of colonoscopy in the NHS BCSP and
      describe new and established measures to assess and maintain quality. DESIGN: The
      NHS BCSP database collects detailed data on all screening colonoscopies.
      Prospectively collected data from the first 3 years of the programme (August 2006
      to August 2009) were analysed. Colonoscopy quality indicators (adenoma detection
      rate (ADR), polyp detection rate, colonoscopy withdrawal time, caecal intubation
      rate, rectal retroversion rate, polyp retrieval rate, mean sedation doses,
      patient comfort scores, bowel preparation quality and adverse event incidence)
      were calculated along with measures of total adenoma detection. RESULTS:
      2,269,983 individuals returned FOB tests leading to 36,460 colonoscopies. Mean
      unadjusted caecal intubation rate was 95.2%, and mean withdrawal time for normal
      procedures was 9.2 min. The mean ADR per colonoscopist was 46.5%. The mean number
      of adenomas per procedure (MAP) was 0.91; the mean number of adenomas per
      positive procedure (MAP+) was 1.94. Perforation occurred after 0.09% of
      procedures. There were no procedure-related deaths. CONCLUSIONS: The NHS BCSP
      provides high-quality colonoscopy, as demonstrated by high caecal intubation
      rate, ADR and comfort scores, and low adverse event rates. Quality is achieved by
      ensuring BCSP colonoscopists meet a high standard before starting screening and
      through ongoing quality assurance. Measuring total adenoma detection (MAP and
      MAP+) as adjuncts to ADR may further enhance quality assurance.

PMID- 21940725
TI  - Growth pattern of serous cystic neoplasms of the pancreas: observational study
      with long-term magnetic resonance surveillance and recommendations for treatment.
AB  - BACKGROUND AND AIMS: The natural history and growth pattern of pancreatic serous
      cystic neoplasms (SCNs) are not well understood. This study was designed in order
      to get insight into the growth rate of SCNs and to suggest recommendations for
      their management. METHODS: Patients with well-documented incidentally discovered
      or minimally symptomatic SCNs who underwent yearly surveillance MRI were analysed
      using a linear mixed model. The growth rate and the effects of different fixed
      factors (sex, personal history of other non-pancreatic malignancies, radiological
      pattern, clinical presentation, tumour site) and random factors (age and tumour
      diameter at the time of diagnosis) on tumour growth were investigated. RESULTS:
      Study population consisted of 145 patients. Estimated overall mean growth rate
      was 0.28 cm/year, but the growth curve analysis showed a different trend between
      the first 7 years after the baseline evaluation (growth rate of 0.1 cm/year) and
      the subsequent period (years 7 to 10, growth rate of 0.6 cm/year, p<0.0001).
      Tests for fixed effects demonstrated that an oligocystic/macrocystic pattern and
      a personal history of other tumours are significant predictors of a more rapid
      mean tumour growth (p<0.0001 and 0.022, growth rates of 0.34 cm/year).
      Furthermore, tumour growth significantly increased with age (p = 0.0001).
      CONCLUSION: Overall, SCNs grow slowly, and an initial non-operative approach is
      feasible in all the asymptomatic or minimally symptomatic patients. The
      oligocystic/macrocystic variant, a history of other non-pancreatic malignancies
      and patients' age impact on tumour growth. In any case, a significant growth is
      unlikely to occur before 7 years from the baseline evaluation. Tumour size at the
      time of diagnosis should not be used for decisional purposes.

PMID- 21940726
TI  - Persistent severe gastrointestinal bleeding in a man with metastatic
      somatostatinoma.

PMID- 21940727
TI  - Multiple chlamydia infection among young women: comparing the role of individual-
      and neighbourhood-level measures of socioeconomic status.
AB  - BACKGROUND: Young women have the highest burden of chlamydia infections, and
      socioeconomic disparities exist. Individual-level measures of socioeconomic
      status (SES) may be difficult to assess for young women. The authors examined
      whether neighbourhood SES provides a useful measure in comparison with individual
      level SES with respect to the burden of multiple chlamydia diagnoses. METHODS: In
      a study of young women with chlamydia (n=233; mean age =21 years), multiple
      infections were assessed with self-report and follow-up testing. General
      estimating equations and pseudo-R(2) were used to assess the roles of individual
      level SES (education and employment) and neighbourhood-level SES (percentage of
      people in census tract of residence below poverty) on multiple chlamydia
      diagnoses. RESULTS: Neither education nor employment was associated with multiple
      chlamydia diagnoses. Women living in high-poverty areas were significantly more
      likely than those living in low-poverty areas to have multiple chlamydia
      diagnoses (adjusted OR 3.46, 95% CI 1.18 to 10.15). This neighbourhood-level
      poverty measure improved model fit by 17%. CONCLUSIONS: Neighborhood-level
      poverty may provide a better measure of SES than individual-level variables as a
      predictor of multiple chlamydia diagnoses in young women and can be useful when
      valid measures of individual-level SES are unavailable.

PMID- 21940728
TI  - Peak systolic velocity indices are more sensitive than end-systolic indices in
      detecting contraction changes assessed by echocardiography in young healthy
      humans.
AB  - AIMS: It remains to be proven whether left ventricular (LV) peak systolic
      velocity indices (peak systolic annulus tissue velocities, ejection velocity, and
      strain rate) are more closely related to contraction than LV end-systolic
      echocardiographic indices (ejection fraction, fractional shortening, systolic
      annulus displacement, global strain, and ejection velocity time integral). The
      study aimed to compare the ability of different echocardiographic methods in
      detecting contraction changes of the LV. METHODS AND RESULTS: Thirty-three
      healthy volunteers (20-32 years) were examined by echocardiography at rest,
      during 10 MUg/kg/min dobutamine (n = 20), and after injection of 15 mg metoprolol
      (n = 20). The effects of dobutamine and metoprolol on peak systolic velocity
      indices and end-systolic indices were compared. The relative increase from rest
      to dobutamine stress and the relative decrease after injection of metoprolol were
      62 and -15% for peak systolic annulus tissue velocity, 60 and -11% for LV outflow
      tract (LVOT) peak velocity, 56 and -11% for peak systolic strain rate, 25 and 1%
      for ejection fraction, 30 and -1% for systolic mitral annulus displacement, 30
      and -5% for LVOT velocity time integral, and 21 and -3% for global strain,
      respectively. The changes of the peak systolic indices were significantly higher
      (all P < 0.05) than the changes of the end-systolic indices. CONCLUSION: Peak
      systolic velocity indices (mitral annulus tissue velocities, ejection velocities,
      and strain rate) exhibited greater variation than end-systolic indices during
      inotropic alterations from which it is assumed that they better reflected LV
      contraction.

PMID- 21940729
TI  - Aldosterone and cortisol predict medium-term left ventricular remodelling
      following myocardial infarction.
AB  - AIMS: Mineralocorticoid receptor (MR) antagonists improve cardiovascular outcomes
      in patients with heart failure complicating acute myocardial infarction (AMI) and
      in chronic heart failure. It is unclear whether these beneficial effects are due
      solely to aldosterone blockade, as MR has a similar affinity for cortisol. We
      examined the relationships between plasma and urinary steroid hormones and left
      ventricular (LV) remodelling in patients with LV dysfunction following AMI.
      METHODS AND RESULTS: Plasma concentrations of renin, aldosterone, and N-terminal
      pro-brain natriuretic peptide (NT-proBNP), and 24 h urinary excretion rates of
      tetrahydroaldosterone (THAldo) and total cortisol metabolites were measured in 93
      patients at a mean of 46 h following AMI prior to contrast-enhanced cardiac
      magnetic resonance (ceCMR). Patients were then randomized to 24 weeks of placebo
      or eplerenone therapy in addition to standard treatment, after which ceCMR was
      repeated. In placebo-treated patients, aldosterone, NT-proBNP, and excretion
      rates of THAldo and total cortisol metabolites were univariate predictors of
      remodelling (i.e. change in LV end-systolic volume index); aldosterone (P =
      0.040) and total cortisol metabolite excretion (P = 0.038) remained independent
      predictors on multivariate analysis. None of the measured biomarkers predicted
      remodelling in the presence of eplerenone. Plasma and urinary aldosterone
      measures, and urinary cortisol metabolites, were not only related to larger
      infarct volumes and greater infarct remodelling over time, but were also higher
      in patients with microvascular obstruction on baseline ceCMR. CONCLUSION:
      Aldosterone and cortisol are associated with medium-term LV remodelling when
      measured early after AMI. The beneficial effects of MR antagonism may relate to
      blockade of both aldosterone- and cortisol-induced MR activation.

PMID- 21940730
TI  - Red cell distribution width and risk for first hospitalization due to heart
      failure: a population-based cohort study.
AB  - AIMS: Red cell distribution width (RDW) has been associated with cardiovascular
      disease, but the relation to heart failure (HF) is unclear. We investigated the
      association between RDW and incidence of first hospitalization due to HF in a
      population-based cohort. METHODS AND RESULTS: Red cell distribution width was
      measured in 26 784 subjects (aged 45-73 years, 61% women), without history of
      myocardial infarction (MI), stroke or HF, who participated in the Malmo Diet and
      Cancer study during 1991-1996. Incidence of HF was identified from the national
      Swedish hospital discharge register during a mean follow-up of 15 years and
      studied in relation to RDW. During follow-up, 773 subjects (55% men) were
      hospitalized due to HF, of whom 166 had an MI before or concurrent with the HF.
      After adjustment for potential confounding factors (including history of coronary
      revascularization, biological, lifestyle, and socio-economic factors), the hazard
      ratios (HR) for HF were 1.47 (95% CI: 1.14-1.89) in the top compared with the
      bottom quartile of RDW (P for trend 0.005), censoring subjects with incident MI
      before HF. The results were similar when all hospitalized HF cases were included
      (HR: 1.33, 1.07-1.66), (P for trend 0.020). After additional adjustment for N
      terminal pro-B-type natriuretic peptide, cystatin C and high-sensitive C-reactive
      protein in a randomly selected subcohort (n= 4761), HR was 1.64 (CI: 0.90-3.00)
      comparing the top vs. bottom quartile of RDW. CONCLUSION: Red cell distribution
      width was found to be associated with long-term incidence of first
      hospitalization due to HF among middle-aged subjects.

PMID- 21940731
TI  - External validation of the UCSF-CAPRA (University of California, San Francisco,
      Cancer of the Prostate Risk Assessment) in Japanese patients receiving radical
      prostatectomy.
AB  - OBJECTIVE: In 2005, the University of California, San Francisco developed the
      Cancer of the Prostate Risk Assessment (UCSF-CAPRA) score as a new risk
      stratification tool. The UCSF-CAPRA, which ranges from 0 to 10 points, consists
      of five clinical variables, prostate-specific antigen, Gleason score, T stage,
      percent of positive biopsies and age. The aim of this study was to validate the
      UCSF-CAPRA score for Japanese prostate cancer patients receiving radical
      prostatectomy using the contemporary Gleason grading. METHODS: From 1999 to 2010,
      211 men who underwent radical prostatectomy were used for validation. Biochemical
      progression-free survival was calculated using the Kaplan-Meier method and the
      UCSF-CAPRA and D'Amico risk categories were compared using the log-rank method.
      The concordance index (c-index) for the UCSF-CAPRA and D'Amico risk
      classification was calculated. RESULTS: Using the UCSF-CAPRA score, 85 (40.3%),
      106 (50.2%) and 20 (9.5%) subjects were stratified as 0-2 points (low risk), 3-5
      points (intermediate risk) and 6-10 points (high risk). Using the D'Amico risk
      criteria, 66 (31.3%), 89 (42.2%) and 56 (26.5%) were stratified as low-,
      intermediate- and high-risk groups, respectively. The Kaplan-Meier analysis
      showed that the UCSF-CAPRA divided the patients significantly into each risk
      category. There was no significant difference between low and intermediate in the
      D'Amico risk classification. The c-index of the UCSF-CAPRA and D'Amico
      classification was 0.755 and 0.713, respectively. CONCLUSION: The UCSF-CAPRA is
      an acceptable risk category tool comparable to that of the D'Amico risk
      classification for Japanese prostate cancer patients receiving radical
      prostatectomy in the contemporary Gleason grading era.

PMID- 21940732
TI  - Diagnostic difficulties of pure intrasinusoidal bone marrow infiltration of non
      Hodgkin's lymphoma: a report of eight cases from India.
AB  - Bone marrow involvement in non-Hodgkin's lymphoma is prognostically important for
      appropriate management. Intrasinusoidal pattern of bone marrow infiltration is
      poorly identified on trephine biopsies. We analyzed the clinical, hematological
      and histopathological spectrum of eight cases of non-Hodgkin's lymphoma showing
      pure intrasinusoidal bone marrow infiltration. Fever, cytopenias and blasts in
      circulation were the indications for bone marrow aspiration and trephine
      biopsies. Flow cytometry on bone marrow and immunohistochemistry on trephine
      sections were done. There were five cases of T-cell hepatosplenic non-Hodgkin's
      lymphoma (three gammadelta T-cell lymphoma) and three B-cell non-Hodgkin's
      lymphoma (two intravascular large B-cell lymphoma and one splenic marginal zone
      lymphoma). Except the cases with intravascular large B-cell lymphoma, all showed
      variable splenomegaly without lymphadenopathy. Immunohistochemistry highlighted
      intrasinusoidal infiltration, which was difficult to discern on hematoxylin and
      eosin. This brief analysis highlights that pure intrasinusoidal infiltration of
      extranodal non-Hodgkin's lymphoma requires a high degree of diagnostic suspicion
      and can be seen in various lymphomas.

PMID- 21940733
TI  - Oncology market research provides a feasible index for standardization of
      colorectal cancer chemotherapy.
AB  - OBJECTIVE: Measures to evaluate standardization of cancer therapy after the major
      revision of guidelines for treatment of cancer are not well established. Our
      objective was to evaluate the usefulness of oncology market research for
      measuring the effect of the guidelines on standardization of colorectal cancer
      chemotherapy. METHODS: The source of data for this analysis was the Oncology
      AnalyzerTM, which provides insight into oncology markets worldwide. We compared
      colorectal cancer chemotherapy before (July 2008-June 2009) and after the major
      revision (July 2009-June 2010) of the Japanese guideline in 2009 to determine the
      effect of the new guidelines on clinical practice. A total of 1425 patients were
      enrolled. RESULTS: We confirmed that guideline revision had an effect on drug
      treatment. Regimens used were in agreement with the recommendations of the new
      guidelines, except that some characteristics depended on hospital specialization.
      A time-course study in 1 year also showed evident change in the use of colorectal
      cancer chemotherapy by the third quarter after the revision. CONCLUSIONS:
      Oncology market research is a useful tool for evaluating standardization of
      colorectal cancer chemotherapy. Furthermore, we expect that this method will
      contribute to the development of more effective cancer therapies.

PMID- 21940734
TI  - Adjuvant radiotherapy for a prostate cancer after renal transplantation and
      review of the literature.
AB  - Renal transplant recipients are a population usually considered at a higher risk
      of malignancies, mostly skin cancer and lymphoproliferative disorder. In recent
      years, prostate cancer in renal transplant recipients has been becoming more
      frequent. This is probably due to the growing age and the longer survival of the
      transplanted patients. We report the case of a 50-year-old man with prostate
      cancer and renal allograft, who received radiotherapy after prostatectomy at the
      Institute of Radiotherapy of the University of Florence. Radiotherapy is part of
      the standard treatment for many cases of prostate cancer. According to the few
      series reported in the literature and also to our experience, radiation therapy
      is feasible also in renal transplant recipients with accurate treatment planning.

PMID- 21940735
TI  - New findings for phenotype-genotype correlations in a large European series of
      holoprosencephaly cases.
AB  - BACKGROUND: Holoprosencephaly (HPE) is the most common forebrain defect in
      humans. It results from incomplete midline cleavage of the prosencephalon.
      METHODS: A large European series of 645 HPE probands (and 699 relatives),
      consisting of 51% fetuses and 49% liveborn children, is reported. RESULTS:
      Mutations in the four main genes involved in HPE (SHH, ZIC2, SIX3, TGIF) were
      identified in 25% of cases. The SHH, SIX3, and TGIF mutations were inherited in
      more than 70% of these cases, whereas 70% of the mutations in ZIC2 occurred de
      novo. Moreover, rearrangements were detected in 22% of the 260 patients screened
      by array comparative genomic hybridisation. 15 probands had two mutations
      providing additional support for the 'multiple-hit process' in HPE. There was a
      positive correlation between the severity of the brain malformation and facial
      features for SHH, SIX3, and TGIF, but no such correlation was found for ZIC2
      mutations. The most severe HPE types were associated with SIX3 and ZIC2
      mutations, whereas microforms were associated with SHH mutations. The study
      focused on the associated brain malformations, including neuronal migration
      defects, which predominated in individuals with ZIC2 mutations, and neural tube
      defects, which were frequently associated with ZIC2 (rachischisis) and TGIF
      mutations. Extracraniofacial features were observed in 27% of the individuals in
      this series (up to 40% of those with ZIC2 mutations) and a significant
      correlation was found between renal/urinary defects and mutations of SHH and
      ZIC2. CONCLUSIONS: An algorithm is proposed based on these new phenotype-genotype
      correlations, to facilitate molecular analysis and genetic counselling for HPE.

PMID- 21940737
TI  - Allelic hierarchy of CDH23 mutations causing non-syndromic deafness DFNB12 or
      Usher syndrome USH1D in compound heterozygotes.
AB  - BACKGROUND: Recessive mutant alleles of MYO7A, USH1C, CDH23, and PCDH15 cause non
      syndromic deafness or type 1 Usher syndrome (USH1) characterised by deafness,
      vestibular areflexia, and vision loss due to retinitis pigmentosa. For CDH23,
      encoding cadherin 23, non-syndromic DFNB12 deafness is associated primarily with
      missense mutations hypothesised to have residual function. In contrast,
      homozygous nonsense, frame shift, splice site, and some missense mutations of
      CDH23, all of which are presumably functional null alleles, cause USH1D. The
      phenotype of a CDH23 compound heterozygote for a DFNB12 allele in trans
      configuration to an USH1D allele is not known and cannot be predicted from
      current understanding of cadherin 23 function in the retina and vestibular
      labyrinth. METHODS AND RESULTS: To address this issue, this study sought CDH23
      compound heterozygotes by sequencing this gene in USH1 probands, and families
      segregating USH1D or DFNB12. Five non-syndromic deaf individuals were identified
      with normal retinal and vestibular phenotypes that segregate compound
      heterozygous mutations of CDH23, where one mutation is a known or predicted USH1
      allele. CONCLUSIONS: One DFNB12 allele in trans configuration to an USH1D allele
      of CDH23 preserves vision and balance in deaf individuals, indicating that the
      DFNB12 allele is phenotypically dominant to an USH1D allele. This finding has
      implications for genetic counselling and the development of therapies for
      retinitis pigmentosa in Usher syndrome. ACCESSION NUMBERS: The cDNA and protein
      Genbank accession numbers for CDH23 and cadherin 23 used in this paper are
      AY010111.2 and AAG27034.2, respectively.

PMID- 21940739
TI  - Breastfeeding of very low-weight infants before and after implementation of the
      baby-friendly hospital initiative.

PMID- 21940740
TI  - Substance use in pregnancy at the Mt. Hope Women's Hospital in Trinidad.

PMID- 21940738
TI  - Identification of a SOX2-dependent subset of tumor- and sphere-forming
      glioblastoma cells with a distinct tyrosine kinase inhibitor sensitivity profile.
AB  - Putative cancer stem cells have been identified in glioblastomas and are
      associated with radio- and chemo-resistance. Further knowledge about these cells
      is thus highly warranted for the development of better glioblastoma therapies.
      Gene expression analyses of 11 high-grade glioma cultures identified 2 subsets,
      designated type A and type B cultures. The type A cultures displayed high
      expression of CXCR4, SOX2, EAAT1, and GFAP and low expression of CNP, PDGFRB,
      CXCL12, and extracellular matrix proteins. Clinical significance of the 2 types
      was indicated by the expression of type A- and type B-defining genes in different
      clinical glioblastoma samples. Classification of glioblastomas with type A- and
      type B-defining genes generated 2 groups of tumors composed predominantly of the
      classical, neural, and/or proneural subsets and the mesenchymal subset,
      respectively. Furthermore, tumors with EGFR mutations were enriched in the group
      of type A samples. Type A cultures possessed a higher capacity to form xenograft
      tumors and neurospheres and displayed low or no sensitivity to monotreatment with
      PDGF- and IGF-1-receptor inhibitors but were efficiently growth inhibited by
      combination treatment with low doses of these 2 inhibitors. Furthermore, siRNA
      induced downregulation of SOX2 reduced sphere formation of type A cultures,
      decreased expression of type A-defining genes, and conferred sensitivity to
      monotreatment with PDGF- and IGF-1-receptor inhibitors. The present study thus
      describes a tumor- and neurosphere-forming SOX2-dependent subset of glioblastoma
      cultures characterized by a gene expression signature similar to that of the
      recently described classical, proneural, and/or neural subsets of glioblastoma.
      The findings that resistance to PDGF- and IGF-1-receptor inhibitors is related to
      SOX2 expression and can be overcome by combination treatment should be considered
      in ongoing efforts to develop novel stem cell-targeting therapies.

PMID- 21940741
TI  - North-South collaboration: a success story.

PMID- 21940743
TI  - Drug administration errors in anaesthesia and beyond.

PMID- 21940742
TI  - Multimodal system designed to reduce errors in recording and administration of
      drugs in anaesthesia: prospective randomised clinical evaluation.
AB  - OBJECTIVE: To clinically evaluate a new patented multimodal system (SAFERSleep)
      designed to reduce errors in the recording and administration of drugs in
      anaesthesia. DESIGN: Prospective randomised open label clinical trial. SETTING:
      Five designated operating theatres in a major tertiary referral hospital.
      PARTICIPANTS: Eighty nine consenting anaesthetists managing 1075 cases in which
      there were 10,764 drug administrations. INTERVENTION: Use of the new system
      (which includes customised drug trays and purpose designed drug trolley drawers
      to promote a well organised anaesthetic workspace and aseptic technique; pre
      filled syringes for commonly used anaesthetic drugs; large legible colour coded
      drug labels; a barcode reader linked to a computer, speakers, and touch screen to
      provide automatic auditory and visual verification of selected drugs immediately
      before each administration; automatic compilation of an anaesthetic record; an on
      screen and audible warning if an antibiotic has not been administered within 15
      minutes of the start of anaesthesia; and certain procedural rules-notably,
      scanning the label before each drug administration) versus conventional practice
      in drug administration with a manually compiled anaesthetic record. MAIN OUTCOME
      MEASURES: Primary: composite of errors in the recording and administration of
      intravenous drugs detected by direct observation and by detailed reconciliation
      of the contents of used drug vials against recorded administrations; and lapses
      in responding to an intermittent visual stimulus (vigilance latency task).
      Secondary: outcomes in patients; analyses of anaesthetists' tasks and assessments
      of workload; evaluation of the legibility of anaesthetic records; evaluation of
      compliance with the procedural rules of the new system; and questionnaire based
      ratings of the respective systems by participants. RESULTS: The overall mean rate
      of drug errors per 100 administrations was 9.1 (95% confidence interval 6.9 to
      11.4) with the new system (one in 11 administrations) and 11.6 (9.3 to 13.9) with
      conventional methods (one in nine administrations) (P = 0.045 for difference).
      Most were recording errors, and, though fewer drug administration errors occurred
      with the new system, the comparison with conventional methods did not reach
      significance. Rates of errors in drug administration were lower when
      anaesthetists consistently applied two key principles of the new system (scanning
      the drug barcode before administering each drug and keeping the voice prompt
      active) than when they did not: mean 6.0 (3.1 to 8.8) errors per 100
      administrations v 9.7 (8.4 to 11.1) respectively (P = 0.004). Lapses in the
      vigilance latency task occurred in 12% (58/471) of cases with the new system and
      9% (40/473) with conventional methods (P = 0.052). The records generated by the
      new system were more legible, and anaesthetists preferred the new system,
      particularly in relation to long, complex, and emergency cases. There were no
      differences between new and conventional systems in respect of outcomes in
      patients or anaesthetists' workload. CONCLUSIONS: The new system was associated
      with a reduction in errors in the recording and administration of drugs in
      anaesthesia, attributable mainly to a reduction in recording errors. Automatic
      compilation of the anaesthetic record increased legibility but also increased
      lapses in a vigilance latency task and decreased time spent watching monitors.
      Trial registration Australian New Zealand Clinical Trials Registry No
      12608000068369.

PMID- 21940744
TI  - An umbilical nodule with cyclical changes.

PMID- 21940745
TI  - Increasing competition in NHS is hampering commissioning.

PMID- 21940746
TI  - Elder abuse.

PMID- 21940747
TI  - Routine testing for HIV is acceptable and effective, show pilot studies.

PMID- 21940748
TI  - Tetherin has negligible activity in restricting hepatitis C virus in hepatocytes.
AB  - We investigated the ability of tetherin, a recently identified antiviral factor,
      in restricting hepatitis C virus (HCV) in the Japanese fulminant hepatitis-1 (JFH
      1) infectious cell culture system. Human hepatocytes (Huh7, Huh7.5.1)
      expressedlow levels of endogenous tetherin, which could be induced by IFN-alpha.
      However, tetherin contributes little to IFN-alpha-mediated anti-HCV JFH-1
      activity. Although tetherin could inhibit Vpu-deleted HIV-1 release, it had
      negligible activity in restricting HCV JFH-1 release from hepatocytes, which was
      evidenced by unaffected levels of intracellular/extracellular HCV RNA and
      infectious virus. The failure of tetherin's anti-HCV activity could not be
      related to the counteraction of HCV, as HCV infection of hepatocytes affected
      neither tetherin expression nor anti-HIV function of tetherin. These observations
      imply that tetherin has negligible activity in the restriction of HCV JFH-1 in
      human hepatocytes.

PMID- 21940749
TI  - A comprehensive view of nuclear receptor cancer cistromes.
AB  - Nuclear receptors comprise a superfamily of ligand-activated transcription
      factors that play important roles in both physiology and diseases including
      cancer. The technologies of chromatin immunoprecipitation followed by array
      hybridization (ChIP-chip) or massively parallel sequencing (ChIP-seq) has been
      used to map, at an unprecedented rate, the in vivo genome-wide binding (cistrome)
      of nuclear receptors in both normal and cancer cells. We developed a curated
      database of 88 nuclear receptor cistrome data sets and other associated high
      throughput data sets including 121 collaborating factor cistromes, 94 epigenomes,
      and 319 transcriptomes. Through integrative analysis of the curated nuclear
      receptor ChIP-chip/seq data sets, we discovered novel factor-specific
      noncanonical motifs that may have important regulatory roles. We also revealed a
      common feature of nuclear receptor pioneering factors to recognize relatively
      short and AT-rich motifs. Most nuclear receptors bind predominantly to introns
      and distal intergenetic regions, and binding sites closer to transcription start
      sites were found to be neither stronger nor more evolutionarily conserved.
      Interestingly, while most nuclear receptors appear to be predominantly
      transcriptional activators, our analysis suggests that the binding of ESR1, RARA,
      and RARG has both activating and repressive effects. Through meta-analysis of
      different omic data of the same cancer cell line model from multiple studies, we
      generated consensus cistrome and expression profiles. We further made
      probabilistic predictions of the nuclear receptor target genes by integrating
      cistrome and transcriptome data and validated the predictions using expression
      data from tumor samples. The final database, with comprehensive cistrome,
      epigenome, and transcriptome data sets and downstream analysis results,
      constitutes a valuable resource for the nuclear receptor and cancer community.

PMID- 21940750
TI  - Sphingosine kinase inhibitors and cancer: seeking the golden sword of Hercules.
AB  - There is considerable evidence that sphingosine kinases play a key role in cancer
      progression, which might involve positive selection of cancer cells that have
      been provided with a survival and growth advantage as a consequence of
      overexpression of the enzyme. Therefore, inhibitors of sphingosine kinase
      represent a novel class of compounds that have potential as anticancer agents.
      Poor inhibitor potency is a major issue that has precluded successful translation
      of these compounds into the clinic. However, recent discoveries have shown that
      sphingosine kinase 1 is an allosteric enzyme and that some inhibitors offer
      improved effectiveness by inducing proteasomal degradation of the enzyme or
      having nanomolar potency. Herein, we provide a perspective about these recent
      developments and highlight the importance of translating basic pharmacologic and
      biochemical findings on sphingosine kinase into new drug discovery programs for
      treatment of cancer.

PMID- 21940751
TI  - Cardiovascular defects in a mouse model of HOXA1 syndrome.
AB  - Congenital heart disease is one of the most common human birth defects, yet many
      genes and pathways regulating heart development remain unknown. A recent study in
      humans revealed that mutations in a single Hox gene, HOXA1 (Athabascan Brainstem
      Dysgenesis Syndrome, Bosley-Salih-Alorainy Syndrome), can cause severe
      cardiovascular malformations, some of which are lethal without surgical
      intervention. Since the discovery of the human syndromes, there have been no
      reports of any Hox mouse mutants with cardiac defects, hampering studies to
      explore the developmental causes of the human disease. In this study, we identify
      severe cardiovascular malformations in a Hox mouse model, which mimic the
      congenital heart defects in HOXA1 syndrome patients. Hoxa1 null mice show defects
      such as interrupted aortic arch, aberrant subclavian artery and Tetralogy of
      Fallot, demonstrating that Hoxa1 is required for patterning of the great arteries
      and outflow tract of the heart. We show that during early embryogenesis, Hoxa1 is
      expressed in precursors of cardiac neural crest cells (NCCs), which populate the
      heart. We further demonstrate that Hoxa1 acts upstream of several genes,
      important for neural crest specification. Thus, our data allow us to suggest a
      model in which Hoxa1 regulates heart development through its influence on cardiac
      NCCs, providing insight into the mechanisms underlying the human disease.

PMID- 21940752
TI  - Retrotransposon activation contributes to fragile X premutation rCGG-mediated
      neurodegeneration.
AB  - Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative
      disorder associated with fragile X premutation carriers. Previous studies have
      shown that fragile X rCGG repeats are sufficient to cause neurodegeneration and
      that the rCGG-repeat-binding proteins Pur alpha and heterogeneous nuclear
      ribonucleoprotein (hnRNP) A2/B1 could modulate rCGG-mediated neuronal toxicity.
      Mobile genetic elements or their remnants populate the genomes, and the
      activities of these elements are tightly controlled for the fitness of host
      genomes in different organisms. Here we provide both biochemical and genetic
      evidence to show that the activation of a specific retrotransposon, gypsy, can
      modulate rCGG-mediated neurodegeneration in an FXTAS Drosophila model. We find
      that one of the rCGG-repeat-binding proteins, hnRNP A2/B1, is involved in this
      process via interaction with heterochromatin protein 1. Knockdown of gypsy RNA by
      RNAi could suppress the neuronal toxicity caused by rCGG repeats. These data
      together point to a surprisingly active role for retrotransposition in
      neurodegeneration.

PMID- 21940753
TI  - Sphingosine kinase 1 is overexpressed and promotes proliferation in human thyroid
      cancer.
AB  - Sphingosine kinase 1 (SphK1), an oncogenic kinase, has been previously found to
      be elevated in various types of human cancer and play a role in tumor development
      and progression. Nevertheless, the biological and clinical significance of SphK1
      in thyroid cancer is largely unknown. Here, we demonstrate that the expression of
      SphK1 is generally up-regulated in thyroid cancer and that its expression level
      is correlated with the degree of thyroid malignancy. Silencing SphK1 by specific
      RNA interference is able to suppress the proliferation of thyroid cancer cells,
      and SphK1 expression level is strongly associated with the expression of
      proliferation cell nuclear antigen in thyroid cancer tissues. Of particular note
      is that depletion of SphK1 results in dephosphorylation of protein kinase B and
      glycogen synthase kinase-3beta and subsequent inactivation of beta-catenin-T-cell
      factor/lymphoid enhancing factor transcriptional activity. Hence, taken together,
      our study has identified SphK1 as a proproliferative oncogenic kinase, an
      Akt/glycogen synthase kinase-3beta/beta-catenin activator, and probably a
      biomarker for thyroid cancer as well.

PMID- 21940754
TI  - Regenerated luminal epithelial cells are derived from preexisting luminal
      epithelial cells in adult mouse prostate.
AB  - Determining the source of regenerated luminal epithelial cells in the adult
      prostate during androgen deprivation and replacement will provide insights into
      the origin of prostate cancer cells and their fate during androgen deprivation
      therapy. Prostate stem cells in the epithelial layer have been suggested to give
      rise to luminal epithelium. However, the extent of stem cell participation to
      prostate regrowth is not clear. In this report, using prostate-specific antigen
      CreER(T2)-based genetic lineage marking/tracing in mice, preexisting luminal
      epithelial cells were shown to be a source of regenerated luminal epithelial
      cells in the adult prostate. Prostatic luminal epithelial cells could survive
      androgen deprivation and were capable of proliferating upon androgen replacement.
      Prostate cancer cells, typically exhibiting a luminal epithelial phenotype, may
      retain this intrinsic capability to survive and regenerate in response to changes
      in androgen signaling, providing part of the mechanism for the ultimate failure
      of androgen deprivation therapy in prostate cancer.

PMID- 21940755
TI  - DNA cytometry testing for cervical cancer screening: approaches and reporting
      standards for new technologies.
AB  - Evaluation of new technologies requires rigorous methods to provide unbiased
      estimates of the performance and so inform future clinical practice. We review
      evidence on DNA cytometry reported earlier in this journal and point to the
      standards for reporting of diagnostic accuracy as a metric against which this
      article can be evaluated. The cross-sectional nature of the data and incomplete
      reporting limit the clinical utility of the study. With application of improved
      reporting standards for diagnostic tests and improved design and evaluation of
      new technologies for screening, we may better inform practices to improve
      clinical outcomes and population health.

PMID- 21940756
TI  - Gene regulation by cohesin in cancer: is the ring an unexpected party to
      proliferation?
AB  - Cohesin is a multisubunit protein complex that plays an integral role in sister
      chromatid cohesion, DNA repair, and meiosis. Of significance, both over- and
      underexpression of cohesin are associated with cancer. It is generally believed
      that cohesin dysregulation contributes to cancer by leading to aneuploidy or
      chromosome instability. For cancers with loss of cohesin function, this idea
      seems plausible. However, overexpression of cohesin in cancer appears to be more
      significant for prognosis than its loss. Increased levels of cohesin subunits
      correlate with poor prognosis and resistance to drug, hormone, and radiation
      therapies. However, if there is sufficient cohesin for sister chromatid cohesion,
      overexpression of cohesin subunits should not obligatorily lead to aneuploidy.
      This raises the possibility that excess cohesin promotes cancer by alternative
      mechanisms. Over the last decade, it has emerged that cohesin regulates gene
      transcription. Recent studies have shown that gene regulation by cohesin
      contributes to stem cell pluripotency and cell differentiation. Of importance,
      cohesin positively regulates the transcription of genes known to be dysregulated
      in cancer, such as Runx1, Runx3, and Myc. Furthermore, cohesin binds with
      estrogen receptor alpha throughout the genome in breast cancer cells, suggesting
      that it may be involved in the transcription of estrogen-responsive genes. Here,
      we will review evidence supporting the idea that the gene regulation function of
      cohesin represents a previously unrecognized mechanism for the development of
      cancer.

PMID- 21940757
TI  - Galactofuranose in eukaryotes: aspects of biosynthesis and functional impact.
AB  - Galactofuranose (Galf) is the five-membered ring form of galactose. It is widely
      distributed among several branches of the eukaryotic kingdom. This review
      highlights recent advances in our understanding of the biosynthesis and function
      of Galf-containing glycoconjugates in fungal Aspergillus spp. and the protozoan
      trypanosomatid parasites. We give an overview of the biosynthetic pathways
      leading to the production of glycolipids, glycoproteins and polysaccharides
      containing Galf in these species and their biological relevance. Remarkably,
      modification of the cell surface caused by Galf absence often results in
      morphological abnormalities and an impaired cell wall function in these
      organisms. Galf-deficient mutants are generally hypersensitive to drugs, exhibit
      a constitutive osmotic stress phenotype and/or have an attenuated virulence.
      Since Galf has never been found in mammals and higher plants, Galf-biosynthetic
      pathways have raised much interest as targets for drug development to combat
      microbial infections.

PMID- 21940758
TI  - Cardiovascular disease: the new epidemic in sub-Saharan Africa.
AB  - Sub-Saharan Africa (SSA) is now facing a double burden of disease where patients
      are suffering from non-communicable diseases such as coronary heart disease,
      along with the burden of the current human immunodeficiency virus (HIV) epidemic.
      Due to this double burden, cardiovascular disease (CVD) prevention and treatment
      has been overlooked, allowing the rates to continue to rise unchecked. A series
      of searches were conducted using PubMed as the primary database. From these
      searches, journal articles were compiled that related to diabetes, obesity and
      smoking rates in SSA. Also, the prevalence of CVD in the USA was reviewed.
      Although the USA has higher rates of CVD now, the rates were on the decline
      compared with SSA. Due to 'Westernization' of SSA, the rates of CVD risk factors,
      such as diabetes, are expected to increase by 50%. Because of this, 80% of CVD
      deaths worldwide took place in developing countries like those in SSA. Although
      HIV/acquired immunodeficiency syndrome (AIDS) is the current epidemic in SSA, CVD
      disease poses a threat as the new epidemic because of the increasing rates of
      these CVD risk factors. Without combating this disease now, SSA is facing an
      epidemiological shift from AIDS to CVD being the leading cause of death.

PMID- 21940759
TI  - Penetrating abdominal aortic ulcers: case reports and review of the literature.
AB  - Atherosclerotic abdominal aortic ulcers are uncommon in contrast to those of the
      thoracic aorta. They present with a variety of symptoms. Computed tomography (CT)
      scans and magnetic resonance imaging (MRI) are the methods of diagnosis.
      Treatment is made easier with the use of endovascular techniques, which have less
      mortality and morbidity than open repair. In this paper, we present three cases
      of penetrating aortic ulcers presenting with abdominal pain. In two of those
      cases, the diagnosis was made by MRI and missed by CT scan. We present a review
      of the literature.

PMID- 21940760
TI  - Acute sleep deprivation: the effects of the AMPAKINE compound CX717 on human
      cognitive performance, alertness and recovery sleep.
AB  - AMPA receptor modulation is a potential novel approach to enhance cognitive
      performance. CX717 is a positive allosteric modulator of the AMPA receptor that
      has shown efficacy in rodent and primate cognition models. CX717 (100 mg, 300 mg
      and 1000 mg) and placebo were studied in 16 healthy male volunteers (18-45 years)
      in a randomized, crossover study. Cognitive function, arousal and recovery sleep
      (by polysomnography) were assessed during the extended wakefulness protocol.
      Placebo condition was associated with significant decrements in cognition,
      particularly at the circadian nadir (between 03:00 and 05:00). Pre-specified
      primary and secondary analyses (general linear mixed modelling, GLMM) at each
      separate time point did not reveal consistent improvements in performance or
      objective alertness with any dose of CX717. Exploratory repeated measures
      analysis, a method used to take into account the influence of individual
      differences, demonstrated an improvement in attention-based task performance
      following the 1000 mg dose. Analysis of the recovery sleep showed that CX717 1000
      mg significantly reduced stage 4 and slow-wave sleep (p <= 0.05) with evidence of
      reduced electroencephalogram (EEG) slow-wave and spindle activity. The study
      suggests that CX717 only at the 1000 mg dose may counteract effects of sleep
      deprivation on attention-based tasks and that it may interfere with subsequent
      recovery sleep.

PMID- 21940761
TI  - Second generation antipsychotics in the treatment of bipolar depression: a
      systematic review and meta-analysis.
AB  - Depressive symptoms and episodes dominate the course of bipolar disorder.
      However, the therapeutic armamentarium for bipolar depression is limited. Recent
      evidence points to the efficacy of second generation antipsychotics (SGAs) for
      the treatment of bipolar depression. We conducted a systematic review and meta
      analysis of the efficacy and safety of SGAs (randomized, double-blind, placebo
      controlled trials; used in monotherapy) in the treatment of adult patients with
      bipolar depression. Publication bias was corrected for by performing similar
      searches using the clinical trials register of the respective pharmaceutical
      companies, the Cochrane Database and ClinicalTrials.gov. Seven published papers
      were identified on the use of aripiprazole, olanzapine and quetiapine. Internal
      validity of the trials was fairly good, external validity only moderate.
      Different outcome measures of efficacy and safety were assessed. When the
      individual trials were looked at, quetiapine and to a lesser extent olanzapine
      demonstrated significant improvement in MADRS (Montgomery-Asberg Depression
      Rating Scale) total scores. This was not demonstrated for aripiprazole. Efficacy
      was hampered by adverse events, such as weight gain, akathisia and
      somnolence/sedation. Both clinical heterogeneity of the included trials and
      statistical heterogeneity of the meta-analytic data were considerable. The number
      of quetiapine trials was disproportionate to the number of trials of aripiprazole
      and olanzapine. Further research is needed to assess differential efficacy of the
      different SGAs and their use in clinical practice.

PMID- 21940762
TI  - Visual salience dominates early visuomotor competition in reaching behavior.
AB  - In this study, we investigated whether visual salience influences the competition
      between potential targets during reach planning. Participants initiated rapid
      pointing movements toward multiple potential targets, with the final target being
      cued only after the reach was initiated. We manipulated visual salience by
      varying the luminance of potential targets. Across two separate experiments, we
      demonstrate that initial reach trajectories are directed toward more salient
      targets, even when there are twice as many targets (and therefore twice the
      likelihood of the final target appearing) on the opposite side of space. We also
      show that this salience bias is time-dependent, as evidenced by the return of
      spatially averaged reach trajectories when participants were given an additional
      500-ms preview of the target display prior to the cue to move. This study shows
      both when and to what extent task-irrelevant luminance differences affect the
      planning of reaches to multiple potential targets.

PMID- 21940763
TI  - Senescent changes in photopic spatial summation.
AB  - Previous studies have demonstrated an inverse relation between the size of the
      complete spatial summation area and ganglion cell density. We hypothesized that
      if this relation is dynamic, the spatial summation area at 6 degrees  nasal would
      expand to compensate for age-related losses of retinal ganglion cells but not in
      the fovea where age-related loss in ganglion cell density is not significant.
      This hypothesis was tested by measuring contrast thresholds with a series of
      Gabor patches varying in size. The spatial summation area was defined by the
      intersection of the segments of a two-branched, piece-wise linear function fitted
      to the data with slopes of -0.5 and 0 on a plot of log threshold vs. log area.
      Results demonstrate a 31% increase in the parafoveal spatial summation area in
      older observers with no significant age-related change in the fovea. The average
      foveal data show a significant increase in thresholds with age. Contrary to the
      foveal data, age comparisons of the parafoveal peak contrast thresholds display
      no significant difference above [corrected] the summation area. Nevertheless, as
      expected from the increase in summation area, expressing the parafoveal
      thresholds as contrast energy reveals a significant difference for stimuli that
      are smaller than the maximal summation area.

PMID- 21940764
TI  - Molecular basis of Rrn3-regulated RNA polymerase I initiation and cell growth.
AB  - Cell growth is regulated during RNA polymerase (Pol) I transcription initiation
      by the conserved factor Rrn3/TIF-IA in yeast/humans. Here we provide a structure
      function analysis of Rrn3 based on a combination of structural biology with in
      vivo and in vitro functional assays. The Rrn3 crystal structure reveals a unique
      HEAT repeat fold and a surface serine patch. Phosphorylation of this patch
      represses human Pol I transcription, and a phospho-mimetic patch mutation
      prevents Rrn3 binding to Pol I in vitro and reduces cell growth and Pol I gene
      occupancy in vivo. Cross-linking indicates that Rrn3 binds Pol I between its
      subcomplexes, AC40/19 and A14/43, which faces the serine patch. The corresponding
      region of Pol II binds the Mediator head that cooperates with transcription
      factor (TF) IIB. Consistent with this, the Rrn3-binding factor Rrn7 is predicted
      to be a TFIIB homolog. This reveals the molecular basis of Rrn3-regulated Pol I
      initiation and cell growth, and indicates a general architecture of eukaryotic
      transcription initiation complexes.

PMID- 21940765
TI  - A randomized trial to improve communication about end-of-life care among patients
      with COPD.
AB  - OBJECTIVE: Patients with COPD consistently express a desire to discuss end-of
      life care with clinicians, but these discussions rarely occur. We assessed
      whether an intervention using patient-specific feedback about preferences for
      discussing end-of-life care would improve the occurrence and quality of
      communication between patients with COPD and their clinicians. METHODS: We
      performed a cluster-randomized trial of clinicians and patients from the
      outpatient clinics at the Veterans Affairs Puget Sound Health Care System. Using
      self-reported questionnaires, we assessed patients' preferences for
      communication, life-sustaining therapy, and experiences at the end of life. The
      intervention clinicians and patients received a one-page patient-specific
      feedback form, based on questionnaire responses, to stimulate conversations. The
      control group completed questionnaires but did not receive feedback. Patient
      reported occurrence and quality of end-of-life communication (QOC) were assessed
      within 2 weeks of a targeted visit. Intention-to-treat regression analyses were
      performed with generalized estimating equations to account for clustering of
      patients within clinicians. RESULTS: Ninety-two clinicians contributed 376
      patients. Patients in the intervention arm reported nearly a threefold higher
      rate of discussions about end-of-life care (unadjusted, 30% vs 11%; P < .001).
      Baseline end-of-life communication was poor (intervention group QOC score, 23.3;
      95% CI, 19.9-26.8; control QOC score, 19.2; 95% CI, 15.9-22.4). Patients in the
      intervention arm reported higher-quality end-of-life communication that was
      statistically significant, although the overall improvement was small (Cohen
      effect size, 0.21). CONCLUSIONS: A one-page patient-specific feedback form about
      preferences for end-of-life care and communication improved the occurrence and
      quality of communication from patients' perspectives. TRIAL REGISTRY:
      ClinicalTrials.gov; No.: NCT00106080; URL: www.clinicaltrials.gov.

PMID- 21940767
TI  - Mast cell inhibition improves pulmonary vascular remodeling in pulmonary
      hypertension.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive
      angioproliferative disease with high morbidity and mortality. Although the
      histopathology is well described, its pathogenesis is largely unknown. We
      previously identified the increased presence of mast cells and their markers in a
      rat model of flow-associated PAH. The aim of this study was to test the effect of
      mast cell stabilization on pulmonary vascular remodeling in experimental PAH.
      METHODS: Rats with flow-associated PAH created by monocrotaline and an aorto
      caval shunt were treated with the mast cell stabilizer cromolyn and compared with
      untreated rats and control rats. Further, we treated a group of rats with PAH
      with an inhibitor (TY-51469) of chymase, one of the mast cell proteases. The
      effects on pulmonary vascular remodeling and hemodynamics were assessed. RESULTS:
      Rats with PAH had increased mast cells, chymase activity, and inflammatory
      markers. Treatment with mast cell stabilizer attenuated pulmonary vascular
      remodeling but not hemodynamics. A lower pulmonary chymase activity correlated
      with more favorable pulmonary vascular remodeling as well as hemodynamics and
      inflammatory markers. CONCLUSIONS: We showed in rats with PAH that mast cell
      stabilization attenuated pulmonary vascular remodeling and that a lower chymase
      activity correlated with more favorable hemodynamics and pulmonary vascular
      remodeling. The results of this experimental study support the concept of the use
      of antiinflammatory therapy by mast cell stabilizers, a group of drugs already
      licensed for clinical use, to attenuate disease progression in PAH.

PMID- 21940768
TI  - Omission of early thromboprophylaxis and mortality in critically ill patients: a
      multicenter registry study.
AB  - BACKGROUND: VTE is a preventable cause of death within hospitals. This study
      aimed to assess the association between omission of early thromboprophylaxis for
      > 24 h after ICU admission and mortality in critically ill patients. METHODS:
      This study involved 175,665 critically ill adult patients admitted to 134 ICUs in
      Australia and New Zealand between 2006 and 2010. RESULTS: The crude ICU and
      hospital mortality in patients who did not receive thromboprophylaxis within 24 h
      of ICU admission was higher than those who were treated with early
      thromboprophylaxis (7.6% vs 6.3%, P = .001; 11.2% vs 10.6%, P = .003,
      respectively), despite the former patients being associated with a slightly lower
      acuity of illness (mean APACHE [Acute Physiology and Chronic Health Evaluation]
      III model predicted mortality, 13% vs 14%; P = .001). The association between
      omission of early thromboprophylaxis and hospital mortality remained significant
      after adjusting for other covariates (OR, 1.22; 95% CI, 1.15-1.30; P = .001),
      particularly for patients with multiple trauma, sepsis, cardiac arrest, and
      preexisting metastatic cancer. The estimated attributable mortality effect of
      omitting early thromboprophylaxis for patients with multiple trauma, sepsis,
      cardiac arrest, and preexisting metastatic cancer was 3.9% (95% CI, 2.2-5.6),
      8.0% (95% CI, 5.6-10.4), 15.4% (95% CI, 11.1-19.8), and 9.4% (95% CI, 6.4-12.4),
      respectively. CONCLUSIONS: Omission of thromboprophylaxis within the first 24 h
      of ICU admission without obvious reasons was associated with an increased risk of
      mortality in critically ill adult patients.

PMID- 21940766
TI  - Race and sex differences in response to endothelin receptor antagonists for
      pulmonary arterial hypertension.
AB  - BACKGROUND: Recently studied therapies for pulmonary arterial hypertension (PAH)
      have improved outcomes among populations of patients, but little is known about
      which patients are most likely to respond to specific treatments. Differences in
      endothelin-1 biology between sexes and between whites and blacks may lead to
      differences in patients' responses to treatment with endothelin receptor
      antagonists (ERAs). METHODS: We conducted pooled analyses of deidentified,
      patient-level data from six randomized placebo-controlled trials of ERAs
      submitted to the US Food and Drug Administration to elucidate heterogeneity in
      treatment response. We estimated the interaction between treatment assignment
      (ERA vs placebo) and sex and between treatment and white or black race in terms
      of the change in 6-min walk distance from baseline to 12 weeks. RESULTS: Trials
      included 1,130 participants with a mean age of 49 years; 21% were men, 74% were
      white, and 6% were black. The placebo-adjusted response to ERAs was 29.7 m (95%
      CI, 3.7-55.7 m) greater in women than in men (P = .03). The placebo-adjusted
      response was 42.2 m for whites and -1.4 m for blacks, a difference of 43.6 m (95%
      CI, -3.5-90.7 m) (P = .07). Similar results were found in sensitivity analyses
      and in secondary analyses using the outcome of absolute distance walked.
      CONCLUSIONS: Women with PAH obtain greater responses to ERAs than do men, and
      whites may experience a greater treatment benefit than do blacks. This
      heterogeneity in treatment-response may reflect pathophysiologic differences
      between sexes and races or distinct disease phenotypes.

PMID- 21940769
TI  - Circulating myeloid-derived suppressor cells are increased and activated in
      pulmonary hypertension.
AB  - BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are increased in
      inflammatory and autoimmune disorders and orchestrate immune cell responses
      therein. Pulmonary hypertension (PH) is associated with inflammation,
      autoimmunity, and lung vascular remodeling. Immature myeloid cells are found in
      the lungs of humans and animals with PH, and we hypothesized that they would be
      increased in the blood of patients with PH compared with control subjects.
      METHODS: Twenty-six children with PH and 10 undergoing cardiac catheterization
      for arrhythmia ablation were studied. Five milliliters of fresh blood were
      analyzed using flow cytometry. Results were confirmed using magnetic bead sorting
      and immunofluorescence, while quantitative polymerase chain reaction and
      intracellular urea concentration assays were used as measures of MDSC arginase-1
      activation. RESULTS: Flow cytometry demonstrated enrichment of circulating MDSCs
      among patients with PH (n = 26; mean, 0.271 * 10(6) cells/mL +/- 0.17; 1.86% of
      CD45(+) population +/- 1.51) compared with control subjects (n = 10; mean, 0.176
      * 10(6) cells/mL +/- 0.05; 0.57% of CD45(+) population +/- 0.29; P < .05). Higher
      numbers of circulating MDSCs correlated to increasing mean pulmonary artery
      pressure (r = 0.510, P < .05). Among patients with PH, female patients had a
      twofold increase in MDSCs compared with male patients. Immunofluorescence
      analysis confirmed the results of flow cytometry. Quantitative reverse
      transcription polymerase chain reaction assay results for arginase-1 and
      measurement of intracellular urea concentration revealed increased activity of
      MDSCs from patients with PH compared with control subjects. CONCLUSIONS:
      Circulating activated MDSCs are significantly increased in children with PH
      compared with control subjects. Further investigation of these cells is
      warranted, and we speculate that they might play significant immunomodulatory
      roles in the disease pathogenesis of PH.

PMID- 21940770
TI  - The timing of tracheotomy in critically ill patients undergoing mechanical
      ventilation: a systematic review and meta-analysis of randomized controlled
      trials.
AB  - BACKGROUND: The objective of this study was to systematically review and
      quantitatively synthesize all randomized controlled trials (RCTs), comparing
      important outcomes in ventilated critically ill patients who received an early or
      late tracheotomy. METHODS: A systematic literature search of PubMed, Cumulative
      Index to Nursing and Allied Health Literature (CINAHL), Embase, the Cochrane
      Central Register of Controlled Trials, the National Research Register, the
      National Health Service Trusts Clinical Trials Register, and the Medical Research
      Council UK database was conducted using specific search terms. Eligible studies
      were RCTs that compared early tracheotomy (ET) with either late tracheotomy or
      prolonged endotracheal intubation in critically ill adult patients. RESULTS:
      Seven trials with 1,044 patients were analyzed. ET did not significantly reduce
      short-term mortality (relative risk [RR], 0.86; 95% CI, 0.65-1.13), long-term
      mortality (RR, 0.84; 95% CI, 0.68-1.04), or incidence of ventilator-associated
      pneumonia (RR, 0.94; 95% CI, 0.77-1.15) in critically ill patients. The timing of
      the tracheotomy was not associated with a markedly reduced duration of mechanical
      ventilation (MV) (weighted mean difference [WMD], -3.90 days; 95% CI, -9.71-1.91)
      or sedation (WMD, -7.09 days; 95% CI, -14.64-0.45), shorter stay in ICU (WMD, 
      6.93 days; 95% CI, -16.50-2.63) or hospital (WMD, 1.45 days; 95% CI, -5.31-8.22),
      or more complications (RR, 0.94; 95% CI, 0.66-1.34). CONCLUSIONS: The present
      meta-analysis suggested that the timing of the tracheotomy did not significantly
      alter important clinical outcomes in critically ill patients. The duration of MV
      and sedation, as well as the long-term outcomes of ET in mechanically ventilated
      patients, should be evaluated in rigorously designed and adequately powered RCTs
      in the future.

PMID- 21940771
TI  - The impact of ischemic heart disease on symptoms, health status, and
      exacerbations in patients with COPD.
AB  - BACKGROUND: Comorbid ischemic heart disease (IHD) is a common and important cause
      of morbidity and mortality in patients with COPD. The impact of IHD on COPD in
      terms of a patient's health status, exercise capacity, and symptoms is not well
      understood. METHODS: We analyzed stable-state data of 386 patients from the
      London COPD cohort between 1995 and 2009 and prospectively collected exacerbation
      data in those who had completed symptom diaries for >= 1 year. RESULTS: Sixty
      four patients (16.6%) with IHD had significantly worse health status as measured
      by the St. George Respiratory Questionnaire (56.9 +/- 18.5 vs 49.1 +/- 19.0, P =
      .003), and a larger proportion of this group reported more severe breathlessness
      in the stable state, with a Medical Research Council dyspnea score of >= 4 (50.9%
      vs 35.1%, P = .029). In subsets of the sample, stable patients with COPD with IHD
      had a higher median (interquartile range [IQR]) serum N-terminal pro-brain
      natriuretic peptide concentration than those without IHD (38 [15, 107] pg/mL vs
      12 [6, 21] pg/mL, P = .004) and a lower exercise capacity (6-min walk distance,
      225 +/- 89 m vs 317 +/- 85 m; P = .002). COPD exacerbations were not more
      frequent in patients with IHD (median, 1.95 [IQR, 1.20, 3.12] vs 1.86 (IQR, 0.75,
      3.96) per year; P = .294), but the median symptom recovery time was 5 days longer
      (17.0 [IQR, 9.8, 24.2] vs 12.0 [IQR, 8.0, 18.0]; P = .009), resulting in
      significantly more days per year reporting exacerbation symptoms (median, 35.4
      [IQR, 13.4, 60.7] vs 22.2 [IQR, 5.7, 42.6]; P = .028). These findings were
      replicated in multivariate analyses allowing for age, sex, FEV(1), and
      exacerbation frequency where applicable. CONCLUSIONS: Comorbid IHD is associated
      with worse health status, lower exercise capacity, and more dyspnea in stable
      patients with COPD as well as with longer exacerbations but not with an increased
      exacerbation frequency.

PMID- 21940772
TI  - Quantification of cardiorespiratory fitness in healthy nonobese and obese men and
      women.
AB  - BACKGROUND: The quantification and interpretation of cardiorespiratory fitness
      (CRF) in obesity is important for adequately assessing cardiovascular
      conditioning, underlying comorbidities, and properly evaluating disease risk. We
      retrospectively compared peak oxygen uptake (VO(2)peak) (ie, CRF) in absolute
      terms, and relative terms (% predicted) using three currently suggested
      prediction equations (Equations R, W, and G). METHODS: There were 19 nonobese and
      66 obese participants. Subjects underwent hydrostatic weighing and incremental
      cycling to exhaustion. Subject characteristics were analyzed by independent t
      test, and % predicted VO(2)peak by a two-way analysis of variance (group and
      equation) with repeated measures on one factor (equation). RESULTS: VO(2)peak
      (L/min) was not different between nonobese and obese adults (2.35 +/- 0.80 [SD]
      vs 2.39 +/- 0.68 L/min). VO(2)peak was higher (P < .02) relative to body mass and
      lean body mass in the nonobese (34 +/- 8 mL/min/kg vs 22 +/- 5 mL/min/kg, 42 +/-
      9 mL/min/lean body mass vs 37 +/- 6 mL/min/lean body mass). Cardiorespiratory
      fitness assessed as % predicted was not different in the nonobese and obese (91%
      +/- 17% predicted vs 95% +/- 15% predicted) using Equation R, while using
      Equation W and G, CRF was lower (P < .05) but within normal limits in the obese
      (94 +/- 15 vs 87 +/- 11; 101% +/- 17% predicted vs 90% +/- 12% predicted,
      respectively), depending somewhat on sex. CONCLUSIONS: Traditional methods of
      reporting VO(2)peak do not allow adequate assessment and quantification of CRF in
      obese adults. Predicted VO(2)peak does allow a normalized evaluation of CRF in
      the obese, although care must be taken in selecting the most appropriate
      prediction equation, especially in women. In general, otherwise healthy obese are
      not grossly deconditioned as is commonly believed, although CRF may be slightly
      higher in nonobese subjects depending on the uniqueness of the prediction
      equation.

PMID- 21940773
TI  - The significance of elevated tumor markers among patients with idiopathic
      pulmonary fibrosis before and after lung transplantation.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a 3
      year median survival. Lung volume and diffusion capacity at rest are usually used
      to monitor the clinical course. Because of high mortality, identification of
      patients at high risk is crucial for treatment strategies such as lung
      transplantation (LTX). This study was designed to determine if tumor markers
      could accurately characterize disease severity and survival in patients with IPF.
      METHODS: The study population consisted of 61 patients with progressive IPF
      referred for LTX. Pulmonary function tests, cardiopulmonary exercise test, 6-min
      walk distance test, and Doppler echocardiogram were assessed at baseline and
      compared with tumor marker levels. Participants were prospectively followed for
      at least 25 months to determine the relationship between test parameters and
      survival. Tumor marker levels were reassessed in patients who underwent LTX.
      Forty-one age- and sex-matched patients (21 LTX recipients) with COPD served as
      control subjects. RESULTS: In the IPF group, nine patients (14.7%) died during
      follow-up and 20 (32.8%) underwent LTX. Univariate analysis showed correlations
      between carbohydrate antigen (CA) 125 and FEV(1) % (P = .0001). CA 19-9 yielded
      the best correlations with exercise parameters and PAP. Significant correlation
      with survival was noted with CA 15-3 (P = .04) only. All tumor marker levels
      decreased significantly following LTX, except CA 125. CA 15-3 had the largest
      decrease (P = .001). Among the COPD group, tumor marker levels before LTX were
      significantly lower compared with the IPF and did not decrease following LTX. No
      patient in either group developed malignancy. CONCLUSIONS: CA 15-3 levels may
      predict disease severity in IPF. Levels decreased in patients with IPF but not
      with COPD following LTX and were not associated with malignancy. This preliminary
      observation suggests that mucin has a role in the pathogenesis of IPF and
      possibly is a marker for disease activity.

PMID- 21940774
TI  - An intronic polymorphism in GRP78 improves chemotherapeutic prediction in non
      small cell lung cancer.
AB  - BACKGROUND: Glucose-regulated protein 78 (GRP78) is involved in not only the
      progression of non-small cell lung cancer (NSCLC) but also chemotherapeutic
      effects. We hypothesized that an intronic polymorphism (rs430397G>A) in GRP78
      affects survival among patients with NSCLC treated with platinum-based
      chemotherapy. METHODS: Blood samples of patients with advanced NSCLC (IIIB/IV)
      were maintained in our specimen bank between 2001 and 2006. Genomic DNA was
      genotyped for rs430397. Associations between rs430397 and platinum-based
      treatment response, overall survival (OS), NSCLC-related survival, progression
      free survival (PFS), and relapses were evaluated. GRP78 RNA and protein in NSCLC
      tissues were tested by real-time polymerase chain reaction and
      immunohistochemistry. RESULTS: The AA genotype is significantly associated with
      platinum-based chemoresistance (P = .019) and NSCLC-related death (P = .022). OS,
      NSCLC-related survival, and PFS of the AA genotype group are decreased compared
      with the GG and AG genotype groups (log-rank P < .05, respectively). The AA group
      showed a higher prevalence of early NSCLC relapses than the AG and GG group (P =
      .030). In addition, the AA genotype showed a significantly increased risk for OS
      (hazard ratio, 1.95) and PFS (hazard ratio, 1.80) compared with the GG group.
      Functional analysis showed that NSCLC tissues with genotype AA have higher GRP78
      RNA and protein expression compared with those carrying GG at rs430397.
      CONCLUSIONS: The rs430397 AA genotype of GRP78 is associated with reduced
      survival and higher prevalence of early relapses in patients with advanced NSCLC
      treated with platinum-based chemotherapy.

PMID- 21940775
TI  - A survey of practices of pulmonary function interpretation in laboratories in
      Northeast Ohio.
AB  - BACKGROUND: Because many different reference equations are available for
      pulmonary function testing (PFT), and because different interpretive strategies
      could affect the interpretation of results, we assessed the variation in practice
      among 17 PFT laboratories. METHODS: PFT laboratory directors/supervisors in 17
      hospitals (near Cleveland, Ohio) were surveyed between September 15, 2010, and
      January 5, 2011. The survey assessed the features of the laboratory, including
      equipment used, types of tests offered, volume of testing, reference equations
      used, and interpretive strategies employed (eg, how normal was determined, how
      tests were actually read, and so forth). RESULTS: Responses were received from
      all 17 laboratories and were verified using submitted sample PFT reports. The
      daily median number of tests performed and patients evaluated were 16 and six,
      respectively. Great variation was observed not only in the choice of reference
      equations for spirometry, but also in the criteria used to define airflow
      obstruction. Great variation was also observed in the reference equations used
      for lung volumes and diffusing capacity, as well as in the criteria used to
      define physiologic derangements such as restriction, hyperinflation, air
      trapping, and impaired diffusing capacity. Only three of the 17 laboratories
      reported and used the "lower limit of normal" to define PFT abnormality.
      CONCLUSIONS: This survey demonstrated substantial variation in PFT laboratory
      practices, including the choice of reference equations, the criteria used to
      define abnormality, and the strategies for interpreting tests. The degree of
      variation raises concern about the consistency of the interpretation of results
      among laboratories and emphasizes the value of compliance with official
      guidelines to drive standardization.

PMID- 21940776
TI  - Association between airway caliber changes with lung inflation and emphysema
      assessed by volumetric CT scan in subjects with COPD.
AB  - BACKGROUND: An increase in airway caliber (airway distensibility) with lung
      inflation is attenuated in COPD. Furthermore, some subjects have a decrease in
      airway caliber with lung inflation. We aimed to test the hypothesis that airway
      caliber increases are lower in subjects with emphysema-predominant (EP) compared
      with airway-predominant (AP) CT scan subtypes. Additionally, we compared clinical
      and CT scan features of subjects with (airway constrictors) and without a
      decrease in airway caliber. METHODS: Based on GOLD (Global Initiative for Chronic
      Obstructive Lung Disease) stages and CT scan subtypes, we created a control group
      (n = 46) and the following matched COPD groups (n = 23 each): GOLD-2-AP, GOLD-2
      EP, GOLD-4-AP, and GOLD-4-EP. From the CT scans of all 138 subjects, we measured
      emphysema, lung volumes, and caliber changes in the third and fourth airway
      generations of two bronchi. We expressed airway distensibility (ratio of airway
      lumen diameter change to lung volume change from end tidal breathing to full
      inspiration) as a global or lobar measure based on normalization by whole-lung or
      lobar volume changes. RESULTS: Global distensibility in the third and fourth
      airway generations was significantly lower in the GOLD-2-EP and GOLD-4-EP groups
      than in control subjects. In GOLD-2 subjects, lobar distensibility of the right
      upper-lobe fourth airway generation was significantly lower in those with EP than
      in those with AP. In multivariate analysis, emphysema was an independent
      determinant of global and lobar airway distensibility. Compared with
      nonconstrictors, airway constrictors experienced more dyspnea, were more
      hyperinflated, and had a higher percentage of emphysema. CONCLUSIONS:
      Distensibility of large- to medium-sized airways is reduced in subjects with an
      EP CT scan subtype. Emphysema seems to alter airway-parenchyma interdependence.
      TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00608764; URL:
      www.clinicaltrials.gov.

PMID- 21940777
TI  - Leptin as a physiological mediator of energetic trade-offs in ecoimmunology:
      implications for disease.
AB  - Organisms must distribute sufficient energy among different and often competing
      physiological systems. This task can become challenging, however, as resources
      are often limiting, resulting in energetic trade-offs. For example, energetically
      based trade-offs between the reproductive and immune systems are common across
      taxa, yet the regulatory mechanisms underlying these trade-offs remain unclear.
      The adipose tissue hormone leptin is an ideal candidate for the modulation of
      energetic trade-offs between different physiological systems as this hormone
      serves as a gage of fat reserves and also modulates a range of physiological
      activities including the reproductive and immune processes. This article presents
      a review of the evidence for the role of leptin as a modulator of energetic trade
      offs with the immune system and suggests its importance in disease ecology. In
      addition, we provide a case study of the ornate tree lizard (Urosaurus ornatus),
      testing whether leptin is involved in mediating a well-documented influence of
      energy state on the trade-off between reproductive activity and immune function.
      Overall, the combined results suggest that leptin serves as a proximate endocrine
      signal of available energy to the immune system, and therefore likely to affect
      susceptibility to diseases.

PMID- 21940778
TI  - Population differentiation in the open sea: insights from the pelagic copepod
      Pleuromamma xiphias.
AB  - Although a number of recent studies of marine holoplankton have reported
      significant genetic structure among populations, little is currently known about
      the biological and oceanographic processes that influence population connectivity
      in oceanic plankton. In order to examine how depth preferences influence
      dispersal in oceanic plankton, I characterized the genetic structure of a copepod
      with diel vertical migration (DVM) (Pleuromamma xiphias), throughout its global
      distribution, and compared these results to those expected given the interaction
      of this species' habitat depth with ocean circulation and bathymetry.
      Mitochondrial COI sequences from 651 individuals from 28 sites in the Indian,
      Pacific, and Atlantic Oceans revealed highly significant genetic differentiation
      both within and among ocean basins. Limited dispersal among distinct pelagic
      provinces seems to have played a major role in population differentiation in this
      species, with strong genetic breaks observed across known oceanographic fronts or
      current systems in all three ocean basins. The Indo-West Pacific (IWP) holds a
      highly distinct genetic population of this species that was sampled in both the
      western Pacific and eastern Indian Oceans. This suggests that the IWP does not
      act as a strong barrier to gene flow between basins, as expected, despite the
      relatively shallow water depth (<200 m) and vertically extensive (>400 m) diel
      migration of this species. A pattern of isolation by distance was observed in the
      Indian Ocean with genetic differentiation among samples down to spatial scales of
      ~800 km, indicating that realized dispersal in P. xiphias occurs over much
      smaller spatial scales than in previously reported oceanic holoplankton. Given
      its highly regionalized population genetic structure, P. xiphias may have some
      capacity to adapt to local oceanographic conditions, and it should not be assumed
      that populations of this species in distinct pelagic biomes will respond in the
      same way to shared physical or climatic forcing.

PMID- 21940779
TI  - RNAcentral: A vision for an international database of RNA sequences.
AB  - During the last decade there has been a great increase in the number of noncoding
      RNA genes identified, including new classes such as microRNAs and piRNAs. There
      is also a large growth in the amount of experimental characterization of these
      RNA components. Despite this growth in information, it is still difficult for
      researchers to access RNA data, because key data resources for noncoding RNAs
      have not yet been created. The most pressing omission is the lack of a
      comprehensive RNA sequence database, much like UniProt, which provides a
      comprehensive set of protein knowledge. In this article we propose the creation
      of a new open public resource that we term RNAcentral, which will contain a
      comprehensive collection of RNA sequences and fill an important gap in the
      provision of biomedical databases. We envision RNA researchers from all over the
      world joining a federated RNAcentral network, contributing specialized knowledge
      and databases. RNAcentral would centralize key data that are currently held
      across a variety of databases, allowing researchers instant access to a single,
      unified resource. This resource would facilitate the next generation of RNA
      research and help drive further discoveries, including those that improve food
      production and human and animal health. We encourage additional RNA database
      resources and research groups to join this effort. We aim to obtain international
      network funding to further this endeavor.

PMID- 21940780
TI  - Inhibition of Id1 augments insulin secretion and protects against high-fat diet
      induced glucose intolerance.
AB  - OBJECTIVE: The molecular mechanisms responsible for pancreatic beta-cell
      dysfunction in type 2 diabetes remain unresolved. Increased expression of the
      helix-loop-helix protein Id1 has been found in islets of diabetic mice and in
      vitro models of beta-cell dysfunction. Here, we investigated the role of Id1 in
      insulin secretion and glucose homeostasis. RESEARCH DESIGN AND METHODS: Id1
      knockout (Id1(-/-)) and wild-type mice were fed a chow or high-fat diet. Glucose
      tolerance, insulin tolerance, beta-cell mass, insulin secretion, and islet gene
      expression were assessed. Small interfering RNA (siRNA) was used to silence Id1
      in MIN6 cells, and responses to chronic palmitate treatment were assessed.
      RESULTS: Id1(-/-) mice exhibited an improved response to glucose challenge and
      were almost completely protected against glucose intolerance induced by high-fat
      diet. This was associated with increased insulin levels and enhanced insulin
      release from isolated islets, whereas energy intake, body weight, fat pad weight,
      beta-cell mass, and insulin action were unchanged. Islets from Id1(-/-) mice
      displayed reduced stress gene expression and were protected against high-fat diet
      induced downregulation of beta-cell gene expression (pancreatic duodenal homeobox
      1, Beta2, Glut2, pyruvate carboxylase, and Gpr40). In MIN6 cells, siRNA-mediated
      inhibition of Id1 enhanced insulin secretion after chronic palmitate treatment
      and protected against palmitate-mediated loss of beta-cell gene expression.
      CONCLUSIONS: These findings implicate Id1 as a negative regulator of insulin
      secretion. Id1 expression plays an essential role in the etiology of glucose
      intolerance, insulin secretory dysfunction, and beta-cell dedifferentiation under
      conditions of increased lipid supply.

PMID- 21940781
TI  - Specific glucose-induced control of insulin receptor substrate-2 expression is
      mediated via Ca2+-dependent calcineurin/NFAT signaling in primary pancreatic
      islet beta-cells.
AB  - OBJECTIVE: Insulin receptor substrate-2 (IRS-2) plays an essential role in
      pancreatic islet beta-cells by promoting growth and survival. IRS-2 turnover is
      rapid in primary beta-cells, but its expression is highly regulated at the
      transcriptional level, especially by glucose. The aim was to investigate the
      molecular mechanism on how glucose regulates IRS-2 gene expression in beta-cells.
      RESEARCH DESIGN AND METHODS: Rat islets were exposed to inhibitors or subjected
      to adenoviral vector-mediated gene manipulations and then to glucose-induced IRS
      2 expression analyzed by real-time PCR and immunoblotting. Transcription factor
      nuclear factor of activated T cells (NFAT) interaction with IRS-2 promoter was
      analyzed by chromatin immunoprecipitation assay and glucose-induced NFAT
      translocation by immunohistochemistry. RESULTS: Glucose-induced IRS-2 expression
      occurred in pancreatic islet beta-cells in vivo but not in liver. Modulating rat
      islet beta-cell Ca(2+) influx with nifedipine or depolarization demonstrated that
      glucose-induced IRS-2 gene expression was dependent on a rise in intracellular
      calcium concentration derived from extracellular sources. Calcineurin inhibitors
      (FK506, cyclosporin A, and a peptide calcineurin inhibitor [CAIN]) abolished
      glucose-induced IRS-2 mRNA and protein levels, whereas expression of a
      constitutively active calcineurin increased them. Specific inhibition of NFAT
      with the peptide inhibitor VIVIT prevented a glucose-induced IRS-2 transcription.
      NFATc1 translocation to the nucleus in response to glucose and association of
      NFATc1 to conserved NFAT binding sites in the IRS-2 promoter were demonstrated.
      CONCLUSIONS: The mechanism behind glucose-induced transcriptional control of IRS
      2 gene expression specific to the islet beta-cell is mediated by the
      Ca(2+)/calcineurin/NFAT pathway. This insight into the IRS-2 regulation could
      provide novel therapeutic means in type 2 diabetes to maintain an adequate
      functional mass.

PMID- 21940782
TI  - FoxO6 integrates insulin signaling with gluconeogenesis in the liver.
AB  - OBJECTIVE: Excessive endogenous glucose production contributes to fasting
      hyperglycemia in diabetes. This effect stems from inept insulin suppression of
      hepatic gluconeogenesis. To understand the underlying mechanisms, we studied the
      ability of forkhead box O6 (FoxO6) to mediate insulin action on hepatic
      gluconeogenesis and its contribution to glucose metabolism. RESEARCH DESIGN AND
      METHODS: We characterized FoxO6 in glucose metabolism in cultured hepatocytes and
      in rodent models of dietary obesity, insulin resistance, or insulin-deficient
      diabetes. We determined the effect of FoxO6 on hepatic gluconeogenesis in
      genetically modified mice with FoxO6 gain- versus loss-of-function and in
      diabetic db/db mice with selective FoxO6 ablation in the liver. RESULTS: FoxO6
      integrates insulin signaling to hepatic gluconeogenesis. In mice, elevated FoxO6
      activity in the liver augments gluconeogenesis, raising fasting blood glucose
      levels, and hepatic FoxO6 depletion suppresses gluconeogenesis, resulting in
      fasting hypoglycemia. FoxO6 stimulates gluconeogenesis, which is counteracted by
      insulin. Insulin inhibits FoxO6 activity via a distinct mechanism by inducing its
      phosphorylation and disabling its transcriptional activity, without altering its
      subcellular distribution in hepatocytes. FoxO6 becomes deregulated in the insulin
      resistant liver, accounting for its unbridled activity in promoting
      gluconeogenesis and correlating with the pathogenesis of fasting hyperglycemia in
      diabetes. These metabolic abnormalities, along with fasting hyperglycemia, are
      reversible by selective inhibition of hepatic FoxO6 activity in diabetic mice.
      CONCLUSIONS: Our data uncover a FoxO6-dependent pathway by which the liver
      orchestrates insulin regulation of gluconeogenesis, providing the proof-of
      concept that selective FoxO6 inhibition is beneficial for curbing excessive
      hepatic glucose production and improving glycemic control in diabetes.

PMID- 21940783
TI  - A novel cellular defect in diabetes: membrane repair failure.
AB  - OBJECTIVE: Skeletal muscle myopathy is a common diabetes complication. One
      possible cause of myopathy is myocyte failure to repair contraction-generated
      plasma membrane injuries. Here, we test the hypothesis that diabetes induces a
      repair defect in skeletal muscle myocytes. RESEARCH DESIGN AND METHODS: Myocytes
      in intact muscle from type 1 (INS2(Akita+/-)) and type 2 (db/db) diabetic mice
      were injured with a laser and dye uptake imaged confocally to test repair
      efficiency. Membrane repair defects were also assessed in diabetic mice after
      downhill running, which induces myocyte plasma membrane disruption injuries in
      vivo. A cell culture model was used to investigate the role of advanced glycation
      end products (AGEs) and the receptor for AGE (RAGE) in development of this repair
      defect. RESULTS: Diabetic myocytes displayed significantly more dye influx after
      laser injury than controls, indicating a repair deficiency. Downhill running also
      resulted in a higher level of repair failure in diabetic mice. This repair defect
      was mimicked in cultured cells by prolonged exposure to high glucose. Inhibition
      of the formation of AGE eliminated this glucose-induced repair defect. However, a
      repair defect could be induced, in the absence of high glucose, by enhancing AGE
      binding to RAGE, or simply by increasing cell exposure to AGE. CONCLUSIONS:
      Because one consequence of repair failure is rapid cell death (via necrosis), our
      demonstration that repair fails in diabetes suggests a new mechanism by which
      myopathy develops in diabetes.

PMID- 21940784
TI  - Third CECOG consensus on the systemic treatment of non-small-cell lung cancer.
AB  - The current third consensus on the systemic treatment of non-small-cell lung
      cancer (NSCLC) builds upon and updates similar publications on the subject by the
      Central European Cooperative Oncology Group (CECOG), which has published such
      consensus statements in the years 2002 and 2005 (Zielinski CC, Beinert T,
      Crawford J et al. Consensus on medical treatment of non-small-cell lung cancer-
      update 2004. Lung Cancer 2005; 50: 129-137). The principle of all CECOG consensus
      is such that evidence-based recommendations for state-of-the-art treatment are
      given upon which all participants and authors of the manuscript have to agree
      (Beslija S, Bonneterre J, Burstein HJ et al. Third consensus on medical treatment
      of metastatic breast cancer. Ann Oncol 2009; 20 (11): 1771-1785). This is of
      particular importance in diseases in which treatment options depend on very
      particular clinical and biologic variables (Zielinski CC, Beinert T, Crawford J
      et al. Consensus on medical treatment of non-small-cell lung cancer--update 2004.
      Lung Cancer 2005; 50: 129-137; Beslija S, Bonneterre J, Burstein HJ et al. Third
      consensus on medical treatment of metastatic breast cancer. Ann Oncol 2009; 20
      (11): 1771-1785). Since the publication of the last CECOG consensus on the
      medical treatment of NSCLC, a series of diagnostic tools for the characterization
      of biomarkers for personalized therapy for NSCLC as well as therapeutic options
      including adjuvant treatment, targeted therapy, and maintenance treatment have
      emerged and strongly influenced the field. Thus, the present third consensus was
      generated that not only readdresses previous disease-related issues but also
      expands toward recent developments in the management of NSCLC. It is the aim of
      the present consensus to summarize minimal quality-oriented requirements for
      individual patients with NSCLC in its various stages based upon levels of
      evidence in the light of a rapidly expanding array of individual therapeutic
      options.

PMID- 21940785
TI  - Celecoxib can prevent capecitabine-related hand-foot syndrome in stage II and III
      colorectal cancer patients: result of a single-center, prospective randomized
      phase III trial.
AB  - BACKGROUND: Hand-foot syndrome (HFS) is the most common adverse event induced by
      capecitabine. Some clinicians think that HFS is a type of inflammation limited to
      the hands and feet and can be prevented with a COX-2 inhibitor (celecoxib).
      METHODS: We designed a single-center, prospective randomized clinical trial to
      test the hypothesis. From August 2008 to December 2010, stage II and III
      colorectal cancer patients receiving capecitabine-based chemotherapy enrolled in
      the trial voluntarily. All patients were divided randomly into two groups treated
      with or without celecoxib. All adverse events were recorded. RESULTS: Grade 1 and
      grade 2 HFS were more common in the capecitabine group than in the
      capecitabine/celecoxib group (74.6% versus 57.4%, P = 0.034, 29.6% versus 14.7% P
      = 0.035). The use of celecoxib (P < 0.001, P = 0.003) and the level of
      dihydropyrimidine dehydrogenase (P = 0.048, P = 0.014) affected the incidence of
      grade 1 and 2 HFS, as determined by log-rank analysis. Multivariate Cox
      proportional hazards regression analysis indicated that the use of celecoxib was
      the only factor that affected the incidence of >= grade 1 HFS [Hazard Ratio (HR):
      0.556, P = 0.001] and >= grade 2 HFS (HR: 0.414, P = 0.005). CONCLUSIONS:
      Celecoxib can be used effectively and safely to prevent capecitabine-related HFS.

PMID- 21940786
TI  - Nectandrin B activates endothelial nitric-oxide synthase phosphorylation in
      endothelial cells: role of the AMP-activated protein kinase/estrogen receptor
      alpha/phosphatidylinositol 3-kinase/Akt pathway.
AB  - We revealed previously that nectandrin B isolated from Myristica fragrans
      (nutmeg, Myristicaceae) functions as a potent AMP-activated protein kinase (AMPK)
      activator and showed its antiobesity effect. In this study, we investigated
      whether nectandrin B affects phosphorylation of endothelial nitric-oxide synthase
      (eNOS) in human endothelial cells. Nectandrin B increased the phosphorylation of
      eNOS and nitric oxide (NO) production in a concentration-dependent manner and
      maximal effect was found at 10 MUg/ml. Nectandrin B activates AMPK, presumably
      via Ca(2+)/calmodulin kinase II activation and nectandrin B-stimulated eNOS
      phosphorylation was reversed by AMPK inhibition. Both the enzyme activity of
      phosphatidylinositol 3-kinase (PI3K) and the estrogen receptor (ER)-dependent
      reporter gene transcription were enhanced by nectandrin B. ERalpha inhibition by
      specific antagonist or small interfering siRNA (siRNA) suppressed nectandrin B
      mediated eNOS phosphorylation. Moreover, AMPK inhibition significantly reversed
      the activation of ER-dependent transcription and PI3K activation in response to
      nectandrin B. Nectandrin B evoked endothelium-dependent relaxation in rat aortic
      rings, and this was blocked by inhibition of AMPK, ER, or PI3K. These results
      suggest that potent AMPK activator nectandrin B enhances NO production via eNOS
      phosphorylation in endothelial cells and ERalpha-dependent PI3K activity is
      required.

PMID- 21940787
TI  - Therapeutic targeting of a novel 6-substituted pyrrolo [2,3-d]pyrimidine thienoyl
      antifolate to human solid tumors based on selective uptake by the proton-coupled
      folate transporter.
AB  - The proton-coupled folate transporter (PCFT) is a proton-folate symporter with an
      acidic pH optimum. By real-time reverse transcription-polymerase chain reaction,
      PCFT was expressed in the majority of 53 human tumor cell lines, with the highest
      levels in Caco-2 (colorectal adenocarcinoma), SKOV3 (ovarian), and HepG2
      (hepatoma) cells. A novel 6-substituted pyrrolo[2,3-d]pyrimidine thienoyl
      antifolate (compound 1) was used to establish whether PCFT can deliver cytotoxic
      drug under pH conditions that mimic the tumor microenvironment. Both 1 and
      pemetrexed (Pmx) inhibited proliferation of R1-11-PCFT4 HeLa cells engineered to
      express PCFT without the reduced folate carrier (RFC) and of HepG2 cells
      expressing both PCFT and RFC. Unlike Pmx, 1 did not inhibit proliferation of R1
      11-RFC6 HeLa cells, which express RFC without PCFT. Treatment of R1-11-PCFT4
      cells at pH 6.8 with 1 or Pmx inhibited colony formation with dose and time
      dependence. Transport of [(3)H]compound 1 into R1-11-PCFT4 and HepG2 cells was
      optimal at pH 5.5 but appreciable at pH 6.8. At pH 6.8, [(3)H]compound 1 was
      metabolized to (3)H-labeled polyglutamates. Glycinamide ribonucleotide
      formyltransferase (GARFTase) in R1-11-PCFT4 cells was inhibited by 1 at pH 6.8,
      as measured by an in situ GARFTase assay, and was accompanied by substantially
      reduced ATP levels. Compound 1 caused S-phase accumulation and a modest level of
      apoptosis. An in vivo efficacy trial with severe combined immunodeficient mice
      implanted with subcutaneous HepG2 tumors showed that compound 1 was active. Our
      findings suggest exciting new therapeutic possibilities to selectively deliver
      novel antifolate drugs via transport by PCFT over RFC by exploiting the acidic
      tumor microenvironment.

PMID- 21940788
TI  - The implications of long-term acute care hospital transfer practices for measures
      of in-hospital mortality and length of stay.
AB  - RATIONALE: The National Quality Forum recently endorsed in-hospital mortality and
      intensive care unit length of stay (LOS) as quality indicators for patients in
      the intensive care unit. These measures may be affected by transferring patients
      to long-term acute care hospitals (LTACs). OBJECTIVES: To quantify the
      implications of LTAC transfer practices on variation in mortality index and LOS
      index for patients in academic medical centers. METHODS: We used a cross
      sectional study design using data reported to the University HealthSystem
      Consortium from 2008-2009. Data were from patients who were mechanically
      ventilated for more than 96 hours. MEASUREMENTS AND MAIN RESULTS: Using linear
      regression, we measured the association between mortality index and LTAC transfer
      rate, with the hospital as the unit of analysis. Similar analyses were conducted
      for LOS index and cost index. A total of 137 hospitals were analyzed, averaging
      534 transfers to LTAC per hospital during the study period. Mean+/-SD in-hospital
      mortality was 24+/-6.4%, and observed LOS was 30.4+/-8.2 days. The mean LTAC
      transfer rate was 15.7+/-13.7%. Linear regression demonstrated a significant
      correlation between transfer rate and mortality index (R2=0.14; P<0.0001) and LOS
      index (R2=0.43; P<0.0001). CONCLUSIONS: LTAC hospital transfer rate has a
      significant impact on reported mortality and LOS indices for patients requiring
      prolonged acute mechanical ventilation. This is an example of factors unrelated
      to quality of medical care or illness severity that must be considered when
      interpreting mortality and LOS as quality indicators.

PMID- 21940789
TI  - Forced vital capacity in patients with idiopathic pulmonary fibrosis: test
      properties and minimal clinically important difference.
AB  - RATIONALE: Forced vital capacity (FVC) is an established measure of pulmonary
      function in idiopathic pulmonary fibrosis (IPF). Evidence regarding its
      measurement properties and minimal clinically important difference (MCID) in this
      population is limited. OBJECTIVES: To assess the reliability, validity, and
      responsiveness of FVC and estimate the MCID in patients with IPF. METHODS: The
      study population included all 1,156 randomized patients in two clinical trials of
      IFN-gamma1b. FVC and other measures of functional status were measured at
      screening or baseline and 24-week intervals thereafter. Reliability was assessed
      based on two proximal measures of FVC, validity was assessed based on
      correlations between FVC and other measures of functional status, and
      responsiveness was assessed based on the relationship between 24-week changes in
      FVC and other measures of functional status. Distribution-based and anchor-based
      methods were used to estimate the MCID. MEASUREMENTS AND MAIN RESULTS:
      Correlation of percent-predicted FVC between measurements (mean interval, 18 d)
      was high (r = 0.93; P < 0.001). Correlations between FVC and other parameters
      were generally weak, with the strongest observed correlation between FVC and
      carbon monoxide diffusing capacity (r = 0.38; P < 0.001). Correlations between
      change in FVC and changes in other parameters were slightly stronger (range, r =
      0.16-0.37; P < 0.001). Importantly, 1-year risk of death was more than twofold
      higher (P < 0.001) in patients with a 24-week decline in FVC between 5% and 10%.
      The estimated MCID was 2-6%. CONCLUSIONS: FVC is a reliable, valid, and
      responsive measure of clinical status in patients with IPF, and a decline of 2
      6%, although small, represents a clinically important difference.

PMID- 21940790
TI  - Prostaglandin E2 as an inhibitory modulator of fibrogenesis in human lung
      allografts.
AB  - RATIONALE: Donor mesenchymal stromal/stem cell (MSC) expansion and fibrotic
      differentiation is associated with development of bronchiolitis obliterans
      syndrome (BOS) in human lung allografts. However, the regulators of fibrotic
      differentiation of these resident mesenchymal cells are not well understood.
      OBJECTIVES: This study examines the role of endogenous and exogenous
      prostaglandin (PG)E2 as a modulator of fibrotic differentiation of human lung
      allograft-derived MSCs. METHODS: Effect of PGE2 on proliferation, collagen
      secretion, and alpha-smooth muscle actin (alpha-SMA) expression was assessed in
      lung-resident MSCs (LR-MSCs) derived from patients with and without BOS. The
      response pathway involved was elucidated by use of specific agonists and
      antagonists. MEASUREMENT AND MAIN RESULTS: PGE2 treatment of LR-MSCs derived from
      normal lung allografts significantly inhibited their proliferation, collagen
      secretion, and alpha-SMA expression. On the basis of pharmacologic and small
      interfering RNA approaches, a PGE2/E prostanoid (EP)2/adenylate cyclase pathway
      was implicated in these suppressive effects. Stimulation of endogenous PGE2
      secretion by IL-1beta was associated with amelioration of their myofibroblast
      differentiation in vitro, whereas its inhibition by indomethacin augmented alpha
      SMA expression. LR-MSCs from patients with BOS secreted significantly less PGE2
      than non-BOS LR-MSCs. Furthermore, BOS LR-MSCs were found to be defective in
      their ability to induce cyclooxygenase-2, and therefore unable to up-regulate
      PGE2 synthesis in response to IL-1beta. BOS LR-MSCs also demonstrated resistance
      to the inhibitory actions of PGE2 in association with a reduction in the EP2/EP1
      ratio. CONCLUSIONS: These data identify the PGE2 axis as an important autocrine
      paracrine brake on fibrotic differentiation of LR-MSCs, a failure of which is
      associated with BOS.

PMID- 21940791
TI  - Overcoming anoikis--pathways to anchorage-independent growth in cancer.
AB  - Anoikis (or cell-detachment-induced apoptosis) is a self-defense strategy that
      organisms use to eliminate 'misplaced' cells, i.e. cells that are in an
      inappropriate location. Occasionally, detached or misplaced cells can overcome
      anoikis and survive for a certain period of time in the absence of the correct
      signals from the extracellular matrix (ECM). If cells are able to adapt to their
      new environment, then they have probably become anchorage-independent, which is
      one of the hallmarks of cancer cells. Anoikis resistance and anchorage
      independency allow tumor cells to expand and invade adjacent tissues, and to
      disseminate through the body, giving rise to metastasis. Thus, overcoming anoikis
      is a crucial step in a series of changes that a tumor cell undergoes during
      malignant transformation. Tumor cells have developed a variety of strategies to
      bypass or overcome anoikis. Some strategies consist of adaptive cellular changes
      that allow the cells to behave as they would in the correct environment, so that
      induction of anoikis is aborted. Other strategies aim to counteract the negative
      effects of anoikis induction by hyperactivating survival and proliferative
      cascades. The recently discovered processes of autophagy and entosis also
      highlight the contribution of these mechanisms to rendering the cells in a
      dormant state until they receive a signal initiated at the ECM, thereby
      circumventing anoikis. In all situations, the final outcome is the ability of the
      tumor to grow and metastasize. A better understanding of the mechanisms
      underlying anoikis resistance could help to counteract tumor progression and
      prevent metastasis formation.

PMID- 21940792
TI  - The regulation of abscission by multi-protein complexes.
AB  - The terminal stage of cytokinesis - a process termed abscission - is the severing
      of the thin intercellular bridge that connects the two daughter cells. Recent
      work provides new insight into the mechanism by which this microtubule-dense
      membrane bridge is resolved, and highlights important roles for multi-protein
      assemblies in different facets of abscission. These include the endosomal sorting
      complex required for transport (ESCRT), which appears to have a decisive role in
      the final scission event, and vesicle tethering complexes, which potentially act
      at an earlier stage, and might serve to prepare the abscission site. Here, we
      review recent studies of the structure, function and regulation of these
      complexes as related to abscission. We focus largely on studies of cytokinesis in
      mammalian cells. However, cell division in other systems, such as plants and
      Archae, is also considered, reflecting the mechanistic conservation of membrane
      scission processes during cell division.

PMID- 21940793
TI  - Role of Template Activating Factor-I as a chaperone in linker histone dynamics.
AB  - Linker histone H1 is a fundamental chromosomal protein involved in the
      maintenance of higher-ordered chromatin organization. The exchange dynamics of
      histone H1 correlates well with chromatin plasticity. A variety of core histone
      chaperones involved in core histone dynamics has been identified, but the
      identity of the linker histone chaperone in the somatic cell nucleus has been a
      long-standing unanswered question. Here we show that Template Activating Factor-I
      (TAF-I, also known as protein SET) is involved in histone H1 dynamics as a linker
      histone chaperone. Among previously identified core histone chaperones and linker
      histone chaperone candidates, only TAF-I was found to be associated specifically
      with histone H1 in mammalian somatic cell nuclei. TAF-I showed linker histone
      chaperone activity in vitro. Fluorescence recovery after photobleaching analyses
      revealed that TAF-I is involved in the regulation of histone H1 dynamics in the
      nucleus. Therefore, we propose that TAF-I is a key molecule that regulates linker
      histone-mediated chromatin assembly and disassembly.

PMID- 21940794
TI  - Polysialic acid controls NCAM signals at cell-cell contacts to regulate focal
      adhesion independent from FGF receptor activity.
AB  - The polysialic acid (polySia) modification of the neural cell adhesion molecule
      NCAM is a key regulator of cell migration. Yet its role in NCAM-dependent or NCAM
      independent modulation of motility and cell-matrix adhesion is largely
      unresolved. Here, we demonstrate that loss of polySia attenuates tumour cell
      migration and augments the number of focal adhesions in a cell-cell contact- and
      NCAM-dependent manner. In the presence or absence of polySia, NCAM never
      colocalised with focal adhesions but was enriched at cell-cell contacts. Focal
      adhesion of polySia- and NCAM-negative cells was enhanced by incubation with
      soluble NCAM or by removing polySia from heterotypic contacts with polySia-NCAM
      positive cells. Focal adhesion was compromised by the src-family kinase inhibitor
      PP2, whereas loss of polySia or exposure to NCAM promoted the association of
      p59(Fyn) with the focal adhesion scaffolding protein paxillin. Unlike other NCAM
      responses, NCAM-induced focal adhesion was not prevented by inhibiting FGF
      receptor activity and could be evoked by NCAM fragments comprising immunoglobulin
      domains three and four but not by the NCAM fibronectin domains alone or by an
      NCAM-derived peptide known to interact with and activate FGF receptors. Together,
      these data indicate that polySia regulates cell motility through NCAM-induced but
      FGF-receptor-independent signalling to focal adhesions.

PMID- 21940795
TI  - WDR36 acts as a scaffold protein tethering a G-protein-coupled receptor, Galphaq
      and phospholipase Cbeta in a signalling complex.
AB  - We identified the WD-repeat-containing protein, WDR36, as an interacting partner
      of the beta isoform of thromboxane A(2) receptor (TPbeta) by yeast two-hybrid
      screening. We demonstrated that WDR36 directly interacts with the C-terminus and
      the first intracellular loop of TPbeta by in vitro GST-pulldown assays. The
      interaction in a cellular context was observed by co-immunoprecipitation, which
      was positively affected by TPbeta stimulation. TPbeta-WDR36 colocalization was
      detected by confocal microscopy at the plasma membrane in non-stimulated HEK293
      cells but the complex translocated to intracellular vesicles following receptor
      stimulation. Coexpression of WDR36 and its siRNA-mediated knockdown,
      respectively, increased and inhibited TPbeta-induced Galphaq signalling.
      Interestingly, WDR36 co-immunoprecipitated with Galphaq, and promoted TPbeta
      Galphaq interaction. WDR36 also associated with phospholipase Cbeta (PLCbeta) and
      increased the interaction between Galphaq and PLCbeta, but prevented
      sequestration of activated Galphaq by GRK2. In addition, the presence of TPbeta
      in PLCbeta immunoprecipitates was augmented by expression of WDR36. Finally,
      disease-associated variants of WDR36 affected its ability to modulate Galphaq
      mediated signalling by TPbeta. We report that WDR36 acts as a new scaffold
      protein tethering a G-protein-coupled receptor, Galphaq and PLCbeta in a
      signalling complex.

PMID- 21940796
TI  - Cofilin cooperates with fascin to disassemble filopodial actin filaments.
AB  - Cells use a large repertoire of proteins to remodel the actin cytoskeleton.
      Depending on the proteins involved, F-actin is organized in specialized
      protrusions such as lamellipodia or filopodia, which serve diverse functions in
      cell migration and sensing. Although factors responsible for directed filament
      assembly in filopodia have been extensively characterized, the mechanisms of
      filament disassembly in these structures are mostly unknown. We investigated how
      the actin-depolymerizing factor cofilin-1 affects the dynamics of
      fascincrosslinked actin filaments in vitro and in live cells. By multicolor total
      internal reflection fluorescence microscopy and fluorimetric assays, we found
      that cofilin-mediated severing is enhanced in fascin-crosslinked bundles compared
      with isolated filaments, and that fascin and cofilin act synergistically in
      filament severing. Immunolabeling experiments demonstrated for the first time
      that besides its known localization in lamellipodia and membrane ruffles,
      endogenous cofilin can also accumulate in the tips and shafts of filopodia. Live
      cell imaging of fluorescently tagged proteins revealed that cofilin is
      specifically targeted to filopodia upon stalling of protrusion and during their
      retraction. Subsequent electron tomography established filopodial actin filament
      and/or bundle fragmentation to precisely correlate with cofilin accumulation.
      These results identify a new mechanism of filopodium disassembly involving both
      fascin and cofilin.

PMID- 21940798
TI  - The POF1B candidate gene for premature ovarian failure regulates epithelial
      polarity.
AB  - POF1B is a candidate gene for premature ovarian failure (POF); it is mainly
      expressed in polarised epithelial tissues, but its function in these tissues and
      the relationship with the disorder are unknown. Here we show colocalisation of
      POF1B with markers of both adherens and tight junctions in human jejunum. The
      tight junction localisation was maintained by the human POF1B stably expressed in
      the MDCK polarised epithelial cell line, whereas it was lost by the POF1B R329Q
      variant associated with POF. Localisation of apico-basal polarity markers and
      ultrastructure of the tight junctions were maintained in cells expressing the
      mutant. However, tight junction assembly was altered, cells were dysmorphic and
      the monolayer organisation was also altered in three-dimensional culture systems.
      Moreover, cells expressing the POF1B R329Q variant showed defects in ciliogenesis
      and cystogenesis as a result of misorientation of primary cilia and mitotic
      division. All of these defects were explained by interference of the mutant with
      the content and organisation of F-actin at the junctions. A role for POF1B in the
      regulation of the actin cytoskeleton was further verified by shRNA silencing of
      the endogenous protein in human intestinal Caco-2 cells. Taken together, these
      data indicate that localisation of POF1B to tight junctions has a key role in the
      organisation of epithelial monolayers by regulating the actin cytoskeleton.

PMID- 21940797
TI  - Nuclear relocalisation of cytoplasmic poly(A)-binding proteins PABP1 and PABP4 in
      response to UV irradiation reveals mRNA-dependent export of metazoan PABPs.
AB  - Poly(A)-binding protein 1 (PABP1) has a fundamental role in the regulation of
      mRNA translation and stability, both of which are crucial for a wide variety of
      cellular processes. Although generally a diffuse cytoplasmic protein, it can be
      found in discrete foci such as stress and neuronal granules. Mammals encode
      several additional cytoplasmic PABPs that remain poorly characterised, and with
      the exception of PABP4, appear to be restricted in their expression to a small
      number of cell types. We have found that PABP4, similarly to PABP1, is a
      diffusely cytoplasmic protein that can be localised to stress granules. However,
      UV exposure unexpectedly relocalised both proteins to the nucleus. Nuclear
      relocalisation of PABPs was accompanied by a reduction in protein synthesis but
      was not linked to apoptosis. In examining the mechanism of PABP relocalisation,
      we found that it was related to a change in the distribution of poly(A) RNA
      within cells. Further investigation revealed that this change in RNA distribution
      was not affected by PABP knockdown but that perturbations that block mRNA export
      recapitulate PABP relocalisation. Our results support a model in which nuclear
      export of PABPs is dependent on ongoing mRNA export, and that a block in this
      process following UV exposure leads to accumulation of cytoplasmic PABPs in the
      nucleus. These data also provide mechanistic insight into reports that
      transcriptional inhibitors and expression of certain viral proteins cause
      relocation of PABP to the nucleus.

PMID- 21940799
TI  - Associations of birth order with early growth and adolescent height, body
      composition, and blood pressure: prospective birth cohort from Brazil.
AB  - Birth weight has been inversely associated with later blood pressure. Firstborns
      tend to have lower birth weight than their later-born peers, but the long-term
      consequences remain unclear. The study objective was to investigate differences
      between firstborn and later-born individuals in early growth patterns, body
      composition, and blood pressure in Brazilian adolescents. The authors studied 453
      adolescents aged 13.3 years from the prospective 1993 Pelotas Birth Cohort.
      Anthropometry, blood pressure, physical activity by accelerometry, and body
      composition by deuterium were measured. Firstborns (n = 143) had significantly
      lower birth weight than later borns (n = 310). At 4 years, firstborns had
      significantly greater weight and height, indicating a substantial overshoot in
      catch-up growth. In adolescence, first borns had significantly greater height and
      blood pressure and a lower activity level. The difference in systolic blood
      pressure could be attributed to variability in early growth and that in diastolic
      blood pressure to reduced physical activity. The magnitude of increased blood
      pressure is clinically significant; hence, birth order is an important
      developmental predictor of cardiovascular risk in this population. Firstborns may
      be more sensitive to environmental factors that promote catch-up growth, and this
      information could potentially be used in nutritional management to prevent catch
      up "overshoot."

PMID- 21940800
TI  - The quality of modern cross-sectional ecologic studies: a bibliometric review.
AB  - The ecologic study design is routinely used by epidemiologists in spite of its
      limitations. It is presently unknown how well the challenges of the design are
      dealt with in epidemiologic research. The purpose of this bibliometric review was
      to critically evaluate the characteristics, statistical methods, and reporting of
      results of modern cross-sectional ecologic papers. A search through 6 major
      epidemiology journals identified all cross-sectional ecologic studies published
      since January 1, 2000. A total of 125 articles met the inclusion requirements and
      were assessed via common evaluative criteria. It was found that a considerable
      number of cross-sectional ecologic studies use unreliable methods or contain
      statistical oversights; most investigators who adjusted their outcomes for age or
      sex did so improperly (64%), statistical validity was a potential issue for 20%
      of regression models, and simple linear regression was the most common analytic
      approach (31%). Many authors omitted important information when discussing the
      ecologic nature of their study (31%), the choice of study design (58%), and the
      susceptibility of their research to the ecological fallacy (49%). These results
      suggest that there is a need for an international set of guidelines that
      standardizes reporting on ecologic studies. Additionally, greater attention
      should be given to the relevant biostatistical literature.

PMID- 21940802
TI  - MR angiography and imaging for the evaluation of middle cerebral artery
      atherosclerotic disease.
AB  - Intracranial atherosclerotic disease may constitute the most common cause of
      ischemic stroke worldwide; yet, in the developed world, imaging research has
      largely focused on extracranial atherosclerosis. Many studies in populations of
      Asian, African, and Hispanic descent demonstrate the preponderance of
      intracranial stenosis compared with carotid stenosis. This review examines the
      clinical presentations of MCA atherosclerosis and stenosis and the use of
      noninvasive MR imaging in the assessment of intracranial vasculature. MRA is a
      well-validated technique that offers great advantage over traditional
      angiography. Advances in high-resolution MR imaging of MCA stenosis have the
      potential to yield excellent visualization of plaque. Future developments in high
      resolution MR imaging to depict intracranial atherosclerosis are explored in this
      review; these advances will guide endovascular therapy and the comparison of
      novel interventions.

PMID- 21940801
TI  - Would our treatment decisions be better justified in the absence of observational
      data?

PMID- 21940803
TI  - Injectable corticosteroid preparations: an embolic risk assessment by static and
      dynamic microscopic analysis.
AB  - BACKGROUND AND PURPOSE: Transforaminal CS injections have been associated with
      severe adverse CNS events, including brain and spinal cord infarction. Our
      purpose was to describe the static and dynamic microscopic appearances of CS
      preparations, with an emphasis on their potential to cause adverse central
      nervous system events by embolic mechanisms during transforaminal injection.
      MATERIALS AND METHODS: Pharmaceutical preparations of nondilute injectable CSs
      were used after appropriate mixing: MPA (40 mg/mL), TA (40 mg/mL), and DSP (8
      mg/2 mL). For dynamic imaging, a novel methodology was devised to replicate the
      flow of crystals within spinal cord arterioles. In addition, CS preparations were
      mixed with plasma to assess for changes in crystal size, morphology, and tendency
      to aggregate. RESULTS: The CS preparations MPA and TA are composed of crystals of
      varying sizes. MPA crystal size range was 0.4-26 MUm (mean, 6.94 MUm), TA crystal
      size range 0.5-110 MUm (mean, 17.4 MUm), and DSP did not contain any significant
      crystals or particles. There was no change in the crystal morphology or
      propensity to aggregate after mixing with local anesthetic. After mixing with
      plasma, the crystals also were unchanged; however, there was a significant
      reduction in the size of aggregates. On dynamic imaging, these aggregates were
      proved to maintain their integrity and to act as potential embolization agents.
      CONCLUSIONS: MPA and TA have a substantial risk of causing infarction by
      embolization if inadvertently injected intra-arterially at the time of TFESI. DSP
      is completely soluble and microscopically has no potential to obstruct
      arterioles. When performing cervical TFESI procedures, the administration of
      insoluble CSs should be avoided.

PMID- 21940804
TI  - Gender differences in language and motor-related fibers in a population of
      healthy preterm neonates at term-equivalent age: a diffusion tensor and
      probabilistic tractography study.
AB  - BACKGROUND AND PURPOSE: Sex differences in white matter structure are
      controversial. In this MR imaging study, we aimed to investigate possible sex
      differences in language and motor-related tracts in healthy preterm neonates by
      using DTI and probabilistic tractography. MATERIALS AND METHODS: Thirty-eight
      preterm neonates (19 boys and 19 girls, age-matched), healthy at term-equivalent
      age and at 12 months were included. TBV was measured individually. Probabilistic
      tractography provided tract volumes, relative tract volumes (volume normalized to
      TBV), FA, MD, and lambda(?) in the SLF, in the TRs, and in the CSTs. Data were
      compared by using independent t tests, and Bonferroni corrections were performed
      to adjust for multiple comparisons. RESULTS: We showed that healthy preterm boys
      had larger TBV than girls. However, girls had statistically significantly larger
      relative tract volumes than boys bilaterally in the parieto-temporal SLF, and in
      the left CST. Moreover, in the left parieto-temporal SLF, a trend toward lower MD
      and lambda(?) was observed in females. CONCLUSIONS: Structural sex differences
      were found in preterm neonates at term-equivalent age in both sides of the
      parieto-temporal SLF and in the left CST. Further studies are necessary to
      investigate whether these structural differences are related to later sex
      differences in language skills and handedness or to the effect of prematurity.

PMID- 21940805
TI  - Role of facet joints in spine pain and image-guided treatment: a review.
AB  - Chronic low back and neck pain remain prevalent medical concerns, with much
      debate regarding the effective evaluation and treatment. Facet disease has been
      implicated as a source of axial nonradiating low back pain. We discuss patient
      evaluation, the role of imaging, current and emerging image-guided therapies for
      facet-related pain, and the increasing importance of outcome-related research in
      this arena.

PMID- 21940806
TI  - Death and destruction in the intra-arterial battle with acute ischemic stroke.

PMID- 21940807
TI  - The CT appearance of a corneal melt: report of 2 cases.
AB  - When the cornea of the eye dissolves, most commonly secondary to infection or
      trauma, the ventral wall of the anterior chamber of the eye is no longer
      supported and thus bulges forward, enlarging the anterior chamber volume. This is
      referred to as a corneal melt, and it has a unique CT appearance that has not
      been previously described.

PMID- 21940808
TI  - Perianeurysmal brain inflammation after flow-diversion treatment.
AB  - BACKGROUND AND PURPOSE: Flow-diverter stents are an alternative treatment for
      challenging and recurrent aneurysms. Thrombosis of the sac is thought to induce
      perianeurysmal brain inflammation, but such phenomena have never been studied in
      flow-diverter devices. We developed imaging data to explain the clinical
      exacerbation of symptoms after flow-diversion treatment. MATERIALS AND METHODS:
      Seventeen patients with unruptured aneurysms were treated by using a flow
      diverter device. Clinical symptoms and angiographic and MR imaging features were
      recorded before and after treatment, during both the acute and chronic phases, to
      look for inflammatory reaction. RESULTS: Seven of the 17 patients (41%) showed a
      delayed clinical aggravation of symptoms posttreatment consisting of a headache
      (n = 7) with aggravation of pre-existing compressive symptoms (n = 4) and the
      appearance of compressive symptoms (n = 1). This clinical deterioration was
      transient; it was observed between 3 and 15 days posttreatment and resolved by
      day 30. MR imaging revealed signs highly suggestive of perianeurysmal
      inflammation with vasogenic edema and blood-brain barrier breakdown. The
      association between MR imaging inflammatory features and clinical aggravation was
      statistically significant. Large aneurysmal size and its proximity to surrounding
      brain tissue were predictive of this inflammatory reaction after flow diversion.
      CONCLUSIONS: The main finding of the series is that MR imaging-defined
      perianeurysmal inflammation is observed with a high frequency after treatment of
      unruptured aneurysms with flow diverters and is, in most cases, associated with a
      transient clinical deterioration.

PMID- 21940809
TI  - The artery of Bernasconi and Cassinari: a morphometric study for superselective
      catheterization.
AB  - BACKGROUND AND PURPOSE: The artery of Bernasconi and Cassinari is an important
      infraclinoid branch of the internal cerebral artery. It is of neuroendovascular
      relevance in view of its supply to complex lesions such as meningiomas and
      arteriovenous malformations in the tentorial and falcotentorial regions. The
      present microanatomic study attempts a morphometric elucidation of this slender
      but important branch of the meningohypophyseal trunk. MATERIALS AND METHODS: The
      origin, course, dimensions, and related variations of the tentorial artery were
      studied in 10 formalin-fixed human cadaveric sides. RESULTS: The tentorial artery
      originated from the meningohypophyseal trunk in all but 1 specimen, in which it
      arose directly from the intracavernous internal carotid artery. In 80% of
      specimens, it took origin as a single branch; as a bifurcation and trifurcation
      in 1 each. It was usually the terminal branch of the meningohypophyseal trunk (in
      90%). In all, 5 distinct microvascular patterns were noted. The mean diameter of
      this artery was 0.7 mm (range, 0.3-0.8 mm; SD, +/- 0.1 mm). The mean length was
      15.4 mm (range, 9-23 mm; SD, +/- 4.4 mm). Its mean distance from the origin of
      the meningohypophyseal trunk was 1.7 mm (range, 1.3-2.3 mm; SD, +/- 0.4 mm). The
      mean distance from the free edge of the tentorium was 3.7 mm (range, 3-5 mm; SD,
      +/- 0.7 mm). CONCLUSIONS: The artery of Bernasconi and Cassinari is an important
      vascular conduit to myriad neoplasms and vascular malformations in the vicinity
      of the tentorium cerebelli. In this era of advanced microneurosurgical techniques
      and superselective endovascular interventions, morphometric knowledge of this
      artery is important for precise and safe management of these lesions.

PMID- 21940810
TI  - Isolation, characterization, and cross-amplification of microsatellite markers
      for the Petunia integrifolia (Solanaceae) complex.
AB  - PREMISE OF THE STUDY: Microsatellite markers were developed for Petunia
      integrifolia subsp. depauperata with an intent to clarify taxonomic questions on
      the P. integrifolia complex, and to identify a purple-flowered parent of P.
      hybrida. METHODS AND RESULTS: We characterized 11 microsatellite loci by
      screening primers developed using an SSR-enriched library. Genotyping of two
      populations resulted in eight polymorphic loci. Cross-species transferability was
      tested for other members of the P. integrifolia complex. CONCLUSIONS: The
      development of these markers may contribute to population genetics studies in
      Petunia, and cross-amplification among related species could be a useful tool for
      research on hybridization and introgression.

PMID- 21940811
TI  - Characterization of microsatellite loci in Erysimum mediohispanicum
      (Brassicaceae) and cross-amplification in related species.
AB  - PREMISE OF THE STUDY: We have developed and optimized microsatellite loci from a
      genomic library of Erysimum mediohispanicum. Microsatellites were also tested for
      cross-amplification in 31 other Erysimum species. METHODS AND RESULTS: A total of
      10 microsatellite loci were successfully amplified. They were polymorphic for 81
      E. mediohispanicum individuals from two locations in Sierra Nevada (southeastern
      Spain), which showed similar patterns of genetic diversity. On average,
      microsatellites had 8.6 alleles per locus and an expected heterozygosity of 0.69.
      Only one locus significantly departed from Hardy-Weinberg equilibrium in both
      locations. Most of the markers successfully amplified in other Erysimum species.
      CONCLUSIONS: The genetic attributes of microsatellite loci will allow their
      application to population genetic studies in Erysimum, such as genetic
      differentiation and structure, gene flow, pollinator-mediated speciation, and
      hybridization studies.

PMID- 21940812
TI  - Development of microsatellite markers for the medicinal plant Isodon rubescens
      (Lamiaceae) and related species.
AB  - PREMISE OF THE STUDY: Microsatellite markers were developed for the medicinal
      plant Isodon rubescens to investigate genetic variability of the species and, in
      future studies, to assess its relation to the content of pharmacologically active
      chemicals produced by the plant. METHODS AND RESULTS: Eleven primer pairs were
      identified and tested in multiple populations of I. rubescens and related species
      (I. henryi, I. enanderianus, I. lophanthoides) from the People's Republic of
      China. The primers amplified dinucleotide repeats and had between two and 12
      alleles per locus in a given population. CONCLUSIONS: These microsatellites will
      be useful for understanding patterns of phytochemical variation in I. rubescens
      and have the potential to be applied to research on evolutionary processes in
      other species of the genus Isodon.

PMID- 21940813
TI  - Testing mechanisms and context dependence of costs of plastic shade avoidance
      responses in Impatiens capensis (Balsaminaceae).
AB  - PREMISE OF THE STUDY: Many plant species elongate their shoots in response to
      neighbor proximity and neighbor height. Although these plastic responses may be
      beneficial in terms of enhancing light interception, they also may have costs in
      terms of increased risk of mechanical failure (i.e., lodging or breaking) because
      of thinner stems. This trade-off between light acquisition and stability may
      shape the evolution of plastic elongation responses to foliage shade. METHODS: In
      a field experiment manipulating elongation phenotypes and densities, we tested
      two hypotheses. We predicted that the risks of mechanical failure depend on
      plastic elongation and/or on characteristics of the immediate neighborhood, such
      as density and neighbor height. Further, we predicted that plants that fail
      mechanically would have reduced fitness. KEY RESULTS: Mechanical failure was
      earlier and more frequent at high density and showed a complex interaction with
      neighborhood characteristics such as relative height of the neighbors and the
      expression of early plasticity. Plants that broke earlier had shorter lifespan
      and lower reproductive output. CONCLUSIONS: Our results show that depending on
      the height and density of the group, plastic elongation responses can remain
      advantageous despite costs of increased risk of mechanical failure of the taller
      stems, as mechanical failure was not associated with strong costs in terms of
      reduced lifespan or seed production. The overall benefits of elongation outweigh
      the costs resulting in selection for elongation at the population level.

PMID- 21940814
TI  - Isolation and characterization of microsatellite loci in Tsoongiodendron odorum
      (Magnoliaceae).
AB  - PREMISE OF THE STUDY: Microsatellite loci were developed in Tsoongiodendron
      odorum, an endangered Magnoliaceae species in subtropical China, for further
      investigation of its conservation genetics. METHODS AND RESULTS: Using the Fast
      Isolation by AFLP of Sequences Containing repeats (FIASCO) protocol, we isolated
      and characterized 12 microsatellite loci from T. odorum. Of the samples analyzed,
      eight were polymorphic and four were monomorphic. CONCLUSIONS: These
      characterized markers will enable genetic diversity, gene flow, and mating system
      studies of T. odorum, which are highly valuable for formulating conservation
      strategies.

PMID- 21940815
TI  - A current viewpoint of lymphangioleiomyomatosis supporting immunotherapeutic
      treatment options.
AB  - Lymphangioleiomyomatosis (LAM) leads to hyperproliferation of abnormal smooth
      muscle cells in the lungs, associated with diffuse pulmonary parenchymal cyst
      formation and progressive dyspnea on exertion. The disease targets women of child
      bearing age. Complications include pneumothoraces and chylous pleural effusions.
      Ten-year survival is estimated at 70%, and lung transplantation remains the only
      validated treatment. It has been observed that LAM cells express markers
      associated with melanocytic differentiation, including gp100 and MART-1. Other
      melanocytic markers have also been observed. The same proteins are targeted by T
      cells infiltrating melanoma tumors as well as by T cells infiltrating autoimmune
      vitiligo skin, and these antigens are regarded as relatively immunogenic.
      Consequently, vaccines have been developed for melanoma targeting these and other
      immunogenic melanocyte differentiation proteins. Preliminary data showing
      susceptibility of LAM cells to melanoma derived T cells suggest that vaccines
      targeting melanosomal antigens can be successful in treating LAM.

PMID- 21940816
TI  - Role of urokinase plasminogen activator receptor-associated protein in mouse
      lung.
AB  - Urokinase plasminogen activator receptor-associated protein (uPARAP, or Endo180)
      is a transmembrane endocytic receptor that mediates collagen internalization and
      degradation. uPARAP may be a novel pathway for collagen turnover and matrix
      remodeling in the lung. The function of uPARAP in lung injury has not been
      described. We analyzed the pulmonary mechanics of uPARAP(-/-) and wild-type mice
      at baseline and examined their response after bleomycin instillation. We compared
      collagen internalization in primary mouse lung fibroblasts (MLFs) from wild-type
      and uPARAP(-/-) mice using flow cytometry and fluorescent microscopy, and we
      examined the role of cytokines in regulating uPARAP expression and collagen
      internalization. We show that uPARAP is highly expressed in the lung, and that
      uPARAP(-/-) mice have increased lung elastance at baseline and after injury.
      uPARAP(-/-) mice are protected from changes in lung permeability after acute lung
      injury and have increased collagen content after bleomycin injury. uPARAP is the
      primary pathway for internalization of collagens in MLFs. Furthermore, collagen
      internalization through uPARAP does not require matrix metalloproteinase
      digestion and is independent of integrins. Mediators of lung injury, including
      transforming growth factor-beta, TNF-alpha, and IL-1, down-regulate both uPARAP
      expression and collagen internalization. uPARAP is highly expressed in the murine
      lung, and loss of uPARAP leads to differences in lung mechanics, lung
      permeability, and collagen content after injury. uPARAP is required for collagen
      internalization by MLFs. Thus, uPARAP is a novel pathway that regulates matrix
      remodeling in the lung after injury.

PMID- 21940817
TI  - Fifty years of "the pill": risk reduction and discovery of benefits beyond
      contraception, reflections, and forecast.
AB  - Widely regarded as a revolutionary drug in its early years, "the pill" may be
      considered the first designer or lifestyle drug. Approximately 85% of women in
      the United States will use an oral contraceptive (OC) for an average of 5 years.
      Since the introduction of OCs in the 1960s, both health benefits and safety
      concerns have been attributed to their use. Widespread use of OC formulations by
      women throughout their reproductive life cycle gave rise to concerns about the
      effects of OCs on risk factors for cardiovascular disorders and cancer. In most
      instances, the noncontraceptive benefits of OCs outweigh the potential risks. As
      with many first in class drugs, lessons can be learned from its development and
      use. Indeed, "the pill" played a significant role in reshaping the regulatory
      process for new drugs during the second half of the 20th century. The birth
      control pill celebrates its 50th birthday this year, as women and men celebrate
      five decades of this revolutionary method of family planning. Recent scientific
      and technological advances in genomics, proteomics, new materials, and new drug
      delivery systems, along with a new understanding of reproductive biology, offer
      the promise of new, safe, and effective forms of contraception. In addition to
      the history of OC therapeutic advances and unintended side effects, the
      noncontraceptive health benefits that women experience beyond pregnancy
      prevention are discussed. This article summarizes a symposium presented at the
      50th Anniversary of the Society of Toxicology National Meeting, held from 6 to 10
      March 2011 in Washington, DC.

PMID- 21940818
TI  - Mechanisms of manganese-induced neurotoxicity in primary neuronal cultures: the
      role of manganese speciation and cell type.
AB  - Manganese (Mn) is an essential trace element required for the proper functioning
      of a variety of physiological processes. However, chronic exposures to Mn can
      cause neurotoxicity in humans, especially when it occurs during critical stages
      of the central nervous system development. The mechanisms mediating this
      phenomenon as well as the contribution of Mn speciation and the sensitivity of
      different types of neuronal cells in such toxicity are poorly understood. This
      study was aimed to investigate the mechanisms mediating the toxic effects of
      MnCl(2), Mn(II) citrate, Mn(III) citrate, and Mn(III) pyrophosphate in primary
      cultures of neocortical (CTX) and cerebellar granular (CGC) neurons. Cell
      viability, mitochondrial function, and glutathione levels were evaluated after Mn
      exposure. CGC were significantly more susceptible to Mn-induced toxicity when
      compared with CTX. Moreover, undifferentiated CGC were more vulnerable to Mn
      toxicity than mature neurons. Mitochondrial dysfunction was observed after the
      exposure to all the tested Mn species. Ascorbate protected CGC against Mn-induced
      neurotoxicity, and this event seemed to be related to the dual role of ascorbate
      in neurons, acting as antioxidant and metabolic energetic supplier. CTX were
      protected from Mn-induced toxicity by ascorbate only when coincubated with
      lactate. These findings reinforce and extend the notion of the hazardous effects
      of Mn toward neuronal cells. In addition, the present results indicate that Mn
      induced neurotoxicity is influenced by brain cell types, their origins, and
      developmental stages as well as by the chemical speciation of Mn, thus providing
      important information about Mn-induced developmental neurotoxicity and its risk
      assessment.

PMID- 21940820
TI  - Anti-IL6-receptor-alpha (tocilizumab) does not inhibit human monocyte-derived
      dendritic cell maturation or alloreactive T-cell responses.
AB  - Significant comorbidites and lethality complicate GVHD and its treatment.
      Targeting the cytokine milieu may improve GVHD control; and IL6 is an attractive
      candidate, given its role in dendritic cell activation and T-cell
      differentiation. Tocilizumab is a humanized mAb to IL6-receptor-alpha (IL6R
      alpha), which is Food and Drug Administration-approved for treatment of
      rheumatoid arthritis. Mouse transplant models have demonstrated that IL6 blockade
      also improves GVHD scores and survival. Definitive immunologic effects of IL6
      inhibition have not emerged given inconsistent alterations in regulatory T cells
      (Tregs) and suppression of T-cell proliferation. Despite on-target suppression of
      IL6R-alpha signaling in human monocyte-derived dendritic cells (moDCs) and T
      cells, our data show no effect on moDC maturation/activation, alloreactive T-cell
      proliferation, Treg expansion, or allogeneic Th1/Th17 responses in vitro. These
      findings merit attention in any clinical trials of tocilizumab for GVHD
      prevention or treatment and provide a rationale for evaluating more specific
      inhibitors of downstream JAK2/STAT3 signaling as well.

PMID- 21940821
TI  - Factor VIII alters tubular organization and functional properties of von
      Willebrand factor stored in Weibel-Palade bodies.
AB  - In endothelial cells, von Willebrand factor (VWF) multimers are packaged into
      tubules that direct biogenesis of elongated Weibel-Palade bodies (WPBs). WPB
      release results in unfurling of VWF tubules and assembly into strings that serve
      to recruit platelets. By confocal microscopy, we have previously observed a
      rounded morphology of WPBs in blood outgrowth endothelial cells transduced to
      express factor VIII (FVIII). Using correlative light-electron microscopy and
      tomography, we now demonstrate that FVIII-containing WPBs have disorganized,
      short VWF tubules. Whereas normal FVIII and FVIII Y1680F interfered with
      formation of ultra-large VWF multimers, release of the WPBs resulted in VWF
      strings of equal length as those from nontransduced blood outgrowth endothelial
      cells. After release, both WPB-derived FVIII and FVIII Y1680F remained bound to
      VWF strings, which however had largely lost their ability to recruit platelets.
      Strings from nontransduced cells, however, were capable of simultaneously
      recruiting exogenous FVIII and platelets. These findings suggest that the
      interaction of FVIII with VWF during WPB formation is independent of Y1680, is
      maintained after WPB release in FVIII-covered VWF strings, and impairs
      recruitment of platelets. Apparently, intra-cellular and extracellular assembly
      of FVIII-VWF complex involves distinct mechanisms, which differ with regard to
      their implications for platelet binding to released VWF strings.

PMID- 21940819
TI  - Inhibition of Rac GTPase signaling and downstream prosurvival Bcl-2 proteins as
      combination targeted therapy in MLL-AF9 leukemia.
AB  - The Rac family of small Rho GTPases coordinates diverse cellular functions in
      hematopoietic cells including adhesion, migration, cytoskeleton rearrangements,
      gene transcription, proliferation, and survival. The integrity of Rac signaling
      has also been found to critically regulate cellular functions in the initiation
      and maintenance of hematopoietic malignancies. Using an in vivo gene targeting
      approach, we demonstrate that Rac2, but not Rac1, is critical to the initiation
      of acute myeloid leukemia in a retroviral expression model of MLL-AF9
      leukemogenesis. However, loss of either Rac1 or Rac2 is sufficient to impair
      survival and growth of the transformed MLL-AF9 leukemia. Rac2 is known to
      positively regulate expression of Bcl-2 family proteins toward a prosurvival
      balance. We demonstrate that disruption of downstream survival signaling through
      antiapoptotic Bcl-2 proteins is implicated in mediating the effects of Rac2
      deficiency in MLL-AF9 leukemia. Indeed, overexpression of Bcl-xL is able to
      rescue the effects of Rac2 deficiency and MLL-AF9 cells are exquisitely sensitive
      to direct inhibition of Bcl-2 family proteins by the BH3-mimetic, ABT-737.
      Furthermore, concurrent exposure to NSC23766, a small-molecule inhibitor of Rac
      activation, increases the apoptotic effect of ABT-737, indicating the Rac/Bcl-2
      survival pathway may be targeted synergistically.

PMID- 21940822
TI  - Regulation of macrophage migration by a novel plasminogen receptor Plg-R KT.
AB  - Localization of plasmin on macrophages and activation of pro-MMP-9 play key roles
      in macrophage recruitment in the inflammatory response. These functions are
      promoted by plasminogen receptors exposing C-terminal basic residues on the
      macrophage surface. Recently, we identified a novel transmembrane plasminogen
      receptor, Plg-R(KT), which exposes a C-terminal lysine on the cell surface. In
      the present study, we investigated the role of Plg-R(KT) in macrophage invasion,
      chemotactic migration, and recruitment. Plg-R(KT) was prominently expressed in
      membranes of human peripheral blood monocytes and monocytoid cells. Plasminogen
      activation by urokinase-type plasminogen activator (uPA) was markedly inhibited
      (by 39%) by treatment with anti-Plg-R(KT) mAb. Treatment of monocytes with anti
      Plg-R(KT) mAb substantially inhibited invasion through the representative matrix,
      Matrigel, in response to MCP-1 (by 54% compared with isotype control).
      Furthermore, chemotactic migration was also inhibited by treatment with anti-Plg
      R(KT) mAb (by 64%). In a mouse model of thioglycollate-induced peritonitis, anti
      Plg-R(KT) mAb markedly inhibited macrophage recruitment (by 58%), concomitant
      with a reduction in pro-MMP-9 activation in the inflamed peritoneum. Treatment
      with anti-Plg-R(KT) mAb did not further reduce the low level of macrophage
      recruitment in plasminogen-null mice. We conclude that Plg-R(KT) plays a key role
      in the plasminogen-dependent regulation of macrophage invasion, chemotactic
      migration, and recruitment in the inflammatory response.

PMID- 21940823
TI  - Iron regulatory protein-1 and -2: transcriptome-wide definition of binding mRNAs
      and shaping of the cellular proteome by iron regulatory proteins.
AB  - Iron regulatory proteins (IRPs) 1 and 2 are RNA-binding proteins that control
      cellular iron metabolism by binding to conserved RNA motifs called iron
      responsive elements (IREs). The currently known IRP-binding mRNAs encode proteins
      involved in iron uptake, storage, and release as well as heme synthesis. To
      systematically define the IRE/IRP regulatory network on a transcriptome-wide
      scale, IRP1/IRE and IRP2/IRE messenger ribonucleoprotein complexes were
      immunoselected, and the mRNA composition was determined using microarrays. We
      identify 35 novel mRNAs that bind both IRP1 and IRP2, and we also report for the
      first time cellular mRNAs with exclusive specificity for IRP1 or IRP2. To further
      explore cellular iron metabolism at a system-wide level, we undertook proteomic
      analysis by pulsed stable isotope labeling by amino acids in cell culture in an
      iron-modulated mouse hepatic cell line and in bone marrow-derived macrophages
      from IRP1- and IRP2-deficient mice. This work investigates cellular iron
      metabolism in unprecedented depth and defines a wide network of mRNAs and
      proteins with iron-dependent regulation, IRP-dependent regulation, or both.

PMID- 21940824
TI  - Anti-Escherichia coli asparaginase antibody levels determine the activity of
      second-line treatment with pegylated E coli asparaginase: a retrospective
      analysis within the ALL-BFM trials.
AB  - Hypersensitivity reactions limit the use of the antileukemic enzyme asparaginase
      (ASE). We evaluated Ab levels against Escherichia coli ASE and ASE activity in
      1221 serum samples from 329 patients with acute lymphoblastic leukemia who had
      received ASE treatment according to the ALL-BFM 2000 or the ALL-REZ BFM 2002
      protocol for primary or relapsed disease. ASE activity during first-line
      treatment with native E coli ASE and second-line treatment with pegylated E coli
      ASE was inversely related to anti-E coli ASE Ab levels (P < .0001; Spearman rank
      order correlation). An effect on ASE activity during second-line treatment with
      pegylated E coli ASE was, however, only observed when anti-E coli ASE Ab levels
      were high (> 200 AU/mL). In the presence of moderate or intermediate Ab levels
      (6.25-200 AU/mL) the switch from native to pegylated E coli ASE resulted in a
      significant increase of ASE activity above the threshold of 100 U/L (P < .05).
      Erwinia chrysanthemi ASE activity was not correlated with anti-E coli ASE Ab
      levels. Erwinia ASE was found to be the best ASE alternative if Ab levels against
      E coli ASE exceed 200 AU/mL. This retrospective analysis is the first to describe
      the relationship between the level of anti-E coli ASE Abs and serum activity of
      pegylated E coli ASE used second-line after native E coli ASE.

PMID- 21940826
TI  - Ironing out fatigue.
AB  - Women who are not anemic but who suffer from fatigue may benefit from iron
      supplementation. In this issue of Blood, Krayenbuhl et al provide strong evidence
      that women complaining of fatigue who were not anemic but who had reduced or
      absent iron stores were symptomatically improved after receiving parenteral iron.
      Given the numbers of women who are iron deficient, the findings could find broad
      application, but work needs to be done to refine the approach to this common
      problem.

PMID- 21940825
TI  - Donor-specific anti-HLA antibodies predict outcome in double umbilical cord blood
      transplantation.
AB  - Using a uniform detection method for donor-specific anti-HLA antibodies (DSAs),
      we sought to determine the effect of preformed DSAs on outcomes in double
      umbilical cord blood transplantation. DSAs were associated with an increased
      incidence of graft failure (5.5% vs 18.2% vs 57.1% for none, single, or dual DSA
      positivity; P = .0001), prolongation of the time to neutrophil engraftment (21 vs
      29 days for none vs any DSA; P = .04), and excess 100-day mortality or relapse
      (23.6% vs 36.4% vs 71.4% for none, single, or dual DSA positivity; P = .01). The
      intensity of DSA reactivity was correlated with graft failure (median of mean
      fluorescent intensity 17 650 vs 1 850; P = .039). There was inferior long-term
      progression-free and overall survival when comparing patients with DSAs against
      both umbilical cord blood units to those without DSAs (3-year progression-free
      survival, 0% vs 33.5%, P = .004; 3-year overall survival 0% vs 45.0%, P = .04).
      We conclude that identification of preformed DSAs in umbilical cord blood
      recipients should be performed and that the use of umbilical cord blood units
      where preformed host DSAs exist should be avoided.

PMID- 21940827
TI  - Fox and Blimp in NK-cell lymphoma.
AB  - In this issue of Blood, Karube and colleagues have identified FOXO3 and PRDM1
      (Blimp1) as tumor suppressor genes with a potentially critical role in the
      pathobiology of extranodal NK/T-cell lymphoma and aggressive NK-cell leukemia.

PMID- 21940828
TI  - Type I-IFNs interfere with GVH responses.
AB  - Just as type I-IFNs interfere with viral replication and autoimmunity, Robb et al
      report that they can also interfere with GVHD and GVL responses after allogeneic
      hematopoietic stemcell transplantation (allo-HSCT).

PMID- 21940829
TI  - The V(H)1-69-expressing marginal zone B cells expanded in HCV-associated mixed
      cryoglobulinemia display proliferative anergy irrespective of CD21(low)
      phenotype.

PMID- 21940830
TI  - A unique case of follicular lymphoma provides insights to the clonal evolution
      from follicular lymphoma in situ to manifest follicular lymphoma.

PMID- 21940831
TI  - Concomitant occurrence of BCR-ABL and JAK2V617F mutation.

PMID- 21940832
TI  - Complete abolishment of coagulant activity in monomeric disulfide-deficient
      tissue factor.

PMID- 21940833
TI  - Haploidentical hematopoietic stem cell transplantation for graft-versus-host
      disease after liver transplantation.

PMID- 21940835
TI  - High-resolution experimental and computational profiling of tissue-specific known
      and novel miRNAs in Arabidopsis.
AB  - Small non-coding RNAs (ncRNAs) are key regulators of plant development through
      modulation of the processing, stability, and translation of larger RNAs. We
      present small RNA data sets comprising more than 200 million aligned Illumina
      sequence reads covering all major cell types of the root as well as four distinct
      developmental zones. MicroRNAs (miRNAs) constitute a class of small ncRNAs that
      are particularly important for development. Of the 243 known miRNAs, 133 were
      found to be expressed in the root, and most showed tissue- or zone-specific
      expression patterns. We identified 66 new high-confidence miRNAs using a
      computational pipeline, PIPmiR, specifically developed for the identification of
      plant miRNAs. PIPmiR uses a probabilistic model that combines RNA structure and
      expression information to identify miRNAs with high precision. Knockdown of three
      of the newly identified miRNAs results in altered root growth phenotypes,
      confirming that novel miRNAs predicted by PIPmiR have functional relevance.

PMID- 21940836
TI  - Comparative methylomics reveals gene-body H3K36me3 in Drosophila predicts DNA
      methylation and CpG landscapes in other invertebrates.
AB  - In invertebrates that harbor functional DNA methylation enzymatic machinery, gene
      bodies are the primary targets for CpG methylation. However, virtually all other
      aspects of invertebrate DNA methylation have remained a mystery until now. Here,
      using a comparative methylomics approach, we demonstrate that Nematostella
      vectensis, Ciona intestinalis, Apis mellifera, and Bombyx mori show two distinct
      populations of genes differentiated by gene-body CpG density. Genome-scale DNA
      methylation profiles for A. mellifera spermatozoa reveal CpG-poor genes are
      methylated in the germline, as predicted by the depletion of CpGs. We find an
      evolutionarily conserved distinction between CpG-poor and GpC-rich genes: The
      former are associated with basic biological processes, the latter with more
      specialized functions. This distinction is strikingly similar to that recently
      observed between euchromatin-associated genes in Drosophila that contain
      intragenic histone 3 lysine 36 trimethylation (H3K36me3) and those that do not,
      even though Drosophila does not display CpG density bimodality or methylation. We
      confirm that a significant number of CpG-poor genes in N. vectensis, C.
      intestinalis, A. mellifera, and B. mori are orthologs of H3K36me3-rich genes in
      Drosophila. We propose that over evolutionary time, gene-body H3K36me3 has
      influenced gene-body DNA methylation levels and, consequently, the gene-body CpG
      density bimodality characteristic of invertebrates that harbor CpG methylation.

PMID- 21940838
TI  - Dose-finding study of peginesatide for anemia correction in chronic kidney
      disease patients.
AB  - BACKGROUND AND OBJECTIVES: Peginesatide is a synthetic, PEGylated,
      investigational, peptide-based erythropoiesis-stimulating agent. We report the
      first assessment of its efficacy and safety in correcting renal anemia in a
      population of 139 nondialysis chronic kidney disease patients. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: Chronic kidney disease patients who were not on
      dialysis and not receiving treatment with erythropoiesis-stimulating agents in
      the 12 weeks before study drug administration were sequentially assigned to one
      of 10 cohorts; cohorts differed in starting peginesatide dose (different body
      weight-based or absolute doses), route of administration (intravenous or
      subcutaneous), and frequency of administration (every 4 or 2 weeks). RESULTS:
      Across all cohorts, 96% of patients achieved a hemoglobin response. A dose
      response relationship was evident for hemoglobin increase. Comparable
      subcutaneous and intravenous peginesatide doses produced similar hemoglobin
      responses. Rapid rates of hemoglobin rise and hemoglobin excursions >13 g/dl
      tended to occur more frequently with every-2-weeks dosing than they did with
      every-4-weeks dosing. The range of final median doses in the every-4-weeks dosing
      groups was 0.019 to 0.043 mg/kg. Across all cohorts, 20% of patients reported
      serious adverse events (one patient had a possibly drug-related serious event)
      and 81% reported adverse events (11.5% reported possibly drug-related events);
      these events were consistent with those routinely observed in this patient
      population. CONCLUSIONS: This study suggests that peginesatide administered every
      4 weeks can increase and maintain hemoglobin in nondialysis chronic kidney
      disease patients. Additional long-term data in larger groups of patients are
      required to further elucidate the efficacy and safety of this peptide-based
      erythropoiesis-stimulating agent.

PMID- 21940837
TI  - Integrating genetic and gene expression evidence into genome-wide association
      analysis of gene sets.
AB  - Single variant or single gene analyses generally account for only a small
      proportion of the phenotypic variation in complex traits. Alternatively, gene set
      or pathway association analyses are playing an increasingly important role in
      uncovering genetic architectures of complex traits through the identification of
      systematic genetic interactions. Two dominant paradigms for gene set analyses are
      association analyses based on SNP genotypes and those based on gene expression
      profiles. However, gene-disease association can manifest in many ways, such as
      alterations of gene expression, genotype, and copy number; thus, an integrative
      approach combining multiple forms of evidence can more accurately and
      comprehensively capture pathway associations. We have developed a single
      statistical framework, Gene Set Association Analysis (GSAA), that simultaneously
      measures genome-wide patterns of genetic variation and gene expression variation
      to identify sets of genes enriched for differential expression and/or trait
      associated genetic markers. Simulation studies illustrate that joint analyses of
      genomic data increase the power to detect real associations when compared with
      gene set methods that use only one genomic data type. The analysis of two human
      diseases, glioblastoma and Crohn's disease, detected abnormalities in previously
      identified disease-associated pathways, such as pathways related to PI3K
      signaling, DNA damage response, and the activation of NFKB. In addition, GSAA
      predicted novel pathway associations, for example, differential genetic and
      expression characteristics in genes from the ABC transporter family in
      glioblastoma and from the HLA system in Crohn's disease. These demonstrate that
      GSAA can help uncover biological pathways underlying human diseases and complex
      traits.

PMID- 21940839
TI  - Late graft loss among pediatric recipients of DCD kidneys.
AB  - BACKGROUND AND OBJECTIVES: Kidney transplantation from donors after cardiac death
      (DCD) provides similar graft survival to donors after brain death (DBD) in adult
      recipients. However, outcomes of DCD kidneys in pediatric recipients remain
      unclear, primarily because of limited sample sizes. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: We identified 137 pediatric (<18 years old)
      recipients of DCD kidneys between 1994 and 2010 using Scientific Registry of
      Transplant Recipients data and compared outcomes with 6059 pediatric recipients
      of DBD kidneys during the same time period, accounting for donor, recipient, and
      transplant characteristics using time-varying Cox regression and matched
      controls. Long-term follow-up (4 years or beyond) was available for 31 DCD
      recipients. RESULTS: Pediatric recipients of DCD kidneys experienced a
      significantly higher rate of delayed graft function (22.0% versus 12.3%; P =
      0.001), although lower than reported delayed graft function rates of DCD grafts
      in adults. Although DCD and DBD graft survival was equal in the early
      postoperative period, graft loss among pediatric recipients of DCD kidneys
      exceeded their DBD counterparts starting 4 years after transplantation. This
      effect was statistically significant in a multivariate Cox model (hazard ratio =
      2.03; 95% confidence interval, 1.21 to 3.39; P = 0.007) and matched-controls
      analysis (hazard ratio = 2.36; 95% confidence interval, 1.11 to 5.03; P = 0.03).
      CONCLUSIONS: A significant increase in DCD graft loss starting 4 years after
      transplantation motivates a cautious approach to the use of DCD kidneys in
      children, in whom long-term graft survival is of utmost importance.

PMID- 21940841
TI  - Sympathetic nerve traffic and asymmetric dimethylarginine in chronic kidney
      disease.
AB  - BACKGROUND AND OBJECTIVES: Sympathetic overactivity and high levels of the
      endogenous inhibitor of NO synthase asymmetric dimethylarginine (ADMA) are
      prevalent risk factors in chronic kidney disease (CKD). DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: In 48 stage 2 to 4 CKD patients, we investigated
      the relationship between efferent postganglionic muscle sympathetic nerve traffic
      (microneurography) and circulating ADMA and analyzed the links between these risk
      factors and estimated GFR (eGFR), proteinuria, and different parameters of left
      ventricular (LV) geometry. RESULTS: CKD patients characterized by sympathetic
      nerve traffic values in the third tertile showed the highest ADMA levels, and
      this association was paralleled by a continuous, positive relationship between
      these two risk factors (r = 0.32, P = 0.03) independent of other confounders.
      Both sympathetic nerve traffic and ADMA were inversely related to eGFR and
      directly to proteinuria and LV geometry. Remarkably, the variance of eGFR,
      proteinuria, and LV geometry explained by sympathetic nerve traffic and ADMA
      largely overlapped because sympathetic nerve traffic but not ADMA was retained as
      a significant correlate of the eGFR (P < 0.001) and of the relative wall
      thickness or the left ventricular mass index/LV volume ratio (P = 0.05) in models
      including both risk factors. ADMA, but not sympathetic nerve traffic, emerged as
      an independent correlate of proteinuria (P = 0.003) in a model including the same
      covariates. CONCLUSIONS: Sympathetic activity and ADMA may share a pathway
      leading to renal disease progression, proteinuria, and LV concentric remodeling
      in CKD patients.

PMID- 21940840
TI  - Correlates of osteoprotegerin and association with aortic pulse wave velocity in
      patients with chronic kidney disease.
AB  - BACKGROUND AND OBJECTIVES: Osteoprotegerin (OPG), a cytokine that regulates bone
      resorption, has been implicated in the process of vascular calcification and
      stiffness. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Serum OPG was measured
      in 351 participants with chronic kidney disease (CKD) from one site of the
      Chronic Renal Insufficiency Cohort Study. Cortical bone mineral content (BMC) was
      measured by quantitative computed tomography in the tibia. Multivariable linear
      regression was used to test the association between serum OPG and traditional
      cardiovascular risk factors, measures of abnormal bone and mineral metabolism,
      and pulse wave velocity. RESULTS: Higher serum OPG levels were associated with
      older age, female gender, greater systolic BP, lower estimated GFR, and lower
      serum albumin. OPG was not associated with measures of abnormal bone or mineral
      metabolism including serum phosphorus, albumin-corrected serum calcium, intact
      parathyroid hormone, bone-specific alkaline phosphatase, or cortical BMC. Among
      226 participants with concurrent aortic pulse wave velocity measurements,
      increasing tertiles of serum OPG were associated with higher aortic pulse wave
      velocity after adjustment for demographics, traditional vascular risk factors,
      and nontraditional risk factors such as estimated GFR, albuminuria, serum
      phosphate, corrected serum calcium, presence of secondary hyperparathyroidism,
      serum albumin, and C-reactive protein or after additional adjustment for cortical
      BMC in a subset (n = 161). CONCLUSIONS: These data support a strong relationship
      between serum OPG and arterial stiffness independent of many potential
      confounders including traditional cardiovascular risk factors, abnormal bone and
      mineral metabolism, and inflammation.

PMID- 21940842
TI  - Pregnancy outcomes in women with chronic kidney disease: a systematic review.
AB  - BACKGROUND AND OBJECTIVES: Pregnant women with chronic kidney disease (CKD) are
      at risk of adverse maternal and fetal outcomes. We conducted a systematic review
      of observational studies that described this risk. DESIGN, SETTING, PARTICIPANTS,
      & MEASUREMENTS: We searched several databases from their date of inception
      through June 2010 for eligible articles published in any language. We included
      any study that reported maternal or fetal outcomes in at least five pregnant
      women in each group with or without CKD. We excluded pregnant women with a
      history of transplantation or maintenance dialysis. RESULTS: We identified 13
      studies. Adverse maternal events including gestational hypertension, pre
      eclampsia, eclampsia, and maternal mortality were reported in 12 studies. There
      were 312 adverse maternal events among 2682 pregnancies in women with CKD
      (weighted average of 11.5%) compared with 500 events in 26,149 pregnancies in
      normal healthy women (weighted average of 2%). One or more adverse fetal outcomes
      such as premature births, intrauterine growth restriction, small for gestational
      age, neonatal mortality, stillbirths, and low birth weight were reported in nine
      of the included studies. Overall, the risk of developing an adverse fetal outcome
      was at least two times higher among women with CKD compared with those without.
      CONCLUSIONS: This review summarizes current available evidence to guide
      physicians in their decision-making, advice, and care for pregnant women with
      CKD. Additional studies are needed to better characterize the risks.

PMID- 21940843
TI  - Chronic kidney disease and albuminuria in children with sickle cell disease.
AB  - BACKGROUND AND OBJECTIVES: Sickle cell nephropathy begins in childhood and may
      progress to renal failure. Albuminuria is a sensitive marker of glomerular damage
      that may indicate early chronic kidney disease (CKD). DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: The aims of this study were to determine the cross
      sectional prevalence and clinical correlates of albuminuria and CKD among
      children with sickle cell disease (SCD). Over a 10-year period (1995 to 2005) 410
      pediatric SCD patients ages 2 to 21 years were enrolled: 261 with hemoglobin SS
      (HbSS) or HbSbeta(0) thalassemia (HbSbeta(0)) and 149 with HbSC or HbSbeta(+)
      thalassemia (HbSbeta(+)). The albumin/creatinine ratio (ACR) of spot-urine
      specimens and serum creatinine were measured; abnormal albuminuria was defined as
      urinary ACR >= 30 mg/g. RESULTS: The prevalence of abnormal albuminuria was 20.7%
      (23.0% in HbSS/HbSbeta(0), 16.8% in HbSC/HbSbeta(+)). Among HbSS/HbSbeta(0),
      abnormal albuminuria was associated with increasing age and lower baseline
      hemoglobin. GFR, estimated in 189 patients using the updated Schwartz formula,
      correlated negatively with age (r = -0.27, P = 0.0002). CKD defined according to
      the Kidney Disease: Improving Global Outcomes study was present in 26.5% (50 of
      189) of patients: stage 1 in 27 (14.8%) and stage 2 in 22 (11.6%). In
      multivariate analysis, age and HbSC/HbSbeta(+) genotype were associated with CKD.
      CONCLUSIONS: This is the first study to stage CKD in children with SCD and
      highlights a high prevalence of albuminuria and glomerular injury early in life.
      Detecting CKD in childhood could allow for earlier intervention and prevention of
      renal failure in adulthood.

PMID- 21940844
TI  - Relation between trunk fat volume and reduction of total lung capacity in obese
      men.
AB  - Reduction in total lung capacity (TLC) in obese men is associated with restricted
      expansion of the thoracic cavity at full inflation. We hypothesized that thoracic
      expansion was reduced by the load imposed by increased total trunk fat volume or
      its distribution. Using MRI, we measured internal and subcutaneous trunk fat and
      total abdominal and thoracic volumes at full inflation in 14 obese men [mean age:
      52.4 yr, body mass index (BMI): 38.8 (range: 36-44) kg/m(2)] and 7 control men
      [mean age: 50.1 yr, BMI: 25.0 (range: 22-27.5) kg/m(2)]. TLC was measured by
      multibreath helium dilution and was restricted (<80% of the predicted value) in
      six obese men (the OR subgroup). All measurements were made with subjects in the
      supine position. Mean total trunk fat volume was 16.65 (range: 12.6-21.8) liters
      in obese men and 6.98 (range: 3.0-10.8) liters in control men. Anthropometry and
      mean total trunk fat volumes were similar in OR men and obese men without
      restriction (the ON subgroup). Mean total intraabdominal volume was 9.41 liters
      in OR men and 11.15 liters in ON men. In obese men, reduced thoracic expansion at
      full inflation and restriction of TLC were not inversely related to a large
      volume of 1) intra-abdominal or total abdominal fat, 2) subcutaneous fat volume
      around the thorax, or 3) total trunk fat volume. In addition, trunk fat volumes
      in obese men were not inversely related to gas volume or estimated intrathoracic
      volume at supine functional residual capacity. In conclusion, this study failed
      to support the hypotheses that restriction of TLC or impaired expansion of the
      thorax at full inflation in middle-aged obese men was simply a consequence of a
      large abdominal volume or total trunk fat volume or its distribution.

PMID- 21940845
TI  - Functional effect of longitudinal heterogeneity in constricted airways before and
      after lung expansion.
AB  - Heterogeneity in narrowing among individual airways is an important contributor
      to airway hyperresponsiveness. This paper investigates the contribution of
      longitudinal heterogeneity (the variability along the airway in cross-sectional
      area and shape) to airway resistance (R(aw)). We analyzed chest high-resolution
      computed tomography scans of 8 asthmatic (AS) and 9 nonasthmatic (NA) subjects
      before and after methacholine (MCh) challenge, and after lung expansion to total
      lung capacity. In each subject, R(aw) was calculated for 35 defined central
      airways with >2 mm diameter. Ignoring the area variability and noncircular shape
      results in an underestimation of R(aw) (%U(total)) that was substantial in some
      airways (~50%) but generally small (median <6%). The average contribution of the
      underestimation of R(aw) caused by longitudinal heterogeneity in the area
      (%U(area)) to %U(total) was 36%, while the rest was due to the noncircularity of
      the shape (%U(shape)). After MCh challenge, %U(area) increased in AS and NA (P <
      0.05). A lung volume increase to TLC reduced %U(total) and %U(area) in both AS
      and NA (P < 0.0001, except for %U(total) in AS with P < 0.01). Only in NA,
      %U(shape) had a significant reduction after increasing lung volume to TLC (P <
      0.005). %U(area) was highly correlated, but not identical to the mean-normalized
      longitudinal heterogeneity in the cross-sectional area [CV(2)(A)] and %U(shape)
      to the average eccentricity of the elliptical shape. This study demonstrates that
      R(aw) calculated assuming a cylindrical shape and derived from an average area
      along its length may, in some airways, substantially underestimate R(aw). The
      observed changes in underestimations of R(aw) with the increase in lung volume to
      total lung capacity may be consistent with, and contribute in part to, the
      differences in effects of deep inhalations in airway function between AS and NA
      subjects.

PMID- 21940846
TI  - Hippocampal functional hyperemia mediated by NMDA receptor/NO signaling in rats
      during mild exercise.
AB  - Current studies have demonstrated that exercise increases regional cerebral blood
      flow (rCBF), an index of neuronal activity. However, neuronal regulation of the
      increased rCBF in the brain parenchyma is poorly understood. We developed a
      running model with rats for monitoring hippocampal cerebral blood flow (Hip-CBF)
      and found that mild treadmill running increases Hip-CBF in a tetrodotoxin
      dependent manner, suggesting that functional hyperemia, an increase in rCBF in
      response to neuronal activation, occurs in the running rat's hippocampus
      (Nishijima T and Soya H. Neurosci Res 54: 186-191, 2006). To further support our
      hypothesis, it was important to discover the neurogenic pathways behind the
      increase in Hip-CBF that occurred during running. Here, we examine the possible
      role of N-methyl-d-aspartate (NMDA) receptor/nitric oxide (NO) signaling and
      group I metabotropic glutamate receptors in mediating the Hip-CBF increase. Hip
      CBF during running was measured by laser-Doppler flowmetry. Intrahippocampal drug
      administration was performed by microdialysis. Mild treadmill running (10 m/min)
      increased Hip-CBF, which was remarkably attenuated by either NMDA receptor
      antagonists (1 mM MK-801) or NO synthase inhibitors (2 mM N(G)-nitro-l-arginine
      methyl ester). However, group I metabotropic glutamate receptor antagonists {1 mM
      7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester + 1 mM 2-methyl-6
      (phenylethynyl)pyridine hydrochloride} augmented the running-induced Hip-CBF
      increase. We also found that rCBF in the olfactory bulb was unchanged with
      running. These results strongly suggest that Hip-CBF during mild exercise is
      regulated locally under hippocampal neuronal activity, mediated mainly through
      NMDA receptor/NO signaling. Collectively, these results, together with our
      previous findings, support our hypothesis that mild exercise elicits neuronal
      activation, which then triggers functional hyperemia in the rat hippocampus.

PMID- 21940847
TI  - Caffeine modulates phosphorylation of insulin receptor substrate-1 and impairs
      insulin signal transduction in rat skeletal muscle.
AB  - Caffeine decreases insulin sensitivity and insulin-stimulated glucose transport
      in skeletal muscle; however, the precise mechanism responsible for this
      deleterious effect is not understood fully. We investigated the effects of
      incubation with caffeine on insulin signaling in rat epitrochlearis muscle.
      Caffeine (>=1 mM, >=15 min) suppressed insulin-stimulated insulin receptor
      substrate (IRS)-1 Tyr(612) phosphorylation in a dose- and time-dependent manner.
      These responses were associated with inhibition of the insulin-stimulated
      phosphorylation of phosphatidylinositol 3-kinase (PI3K) Tyr(458), Akt Ser(473),
      and glycogen synthase kinase-3beta Ser(9) and with inhibition of insulin
      stimulated 3-O-methyl-d-glucose (3MG) transport but not with inhibition of the
      phosphorylation of insulin receptor-beta Tyr(1158/62/63). Furthermore, caffeine
      enhanced phosphorylation of IRS-1 Ser(307) and an IRS-1 Ser(307) kinase,
      inhibitor-kappaB kinase (IKK)-alpha/beta Ser(176/180). Blockade of IKK/IRS-1
      Ser(307) by caffeic acid ameliorated the caffeine-induced downregulation of IRS-1
      Tyr(612) phosphorylation and 3MG transport. Caffeine also increased the
      phosphorylation of IRS-1 Ser(789) and an IRS-1 Ser(789) kinase, 5'-AMP-activated
      protein kinase (AMPK). However, inhibition of IRS-1 Ser(789) and AMPK
      phosphorylation by dantrolene did not rescue the caffeine-induced downregulation
      of IRS-1 Tyr(612) phosphorylation or 3MG transport. In addition, caffeine
      suppressed the phosphorylation of insulin-stimulated IRS-1 Ser(636/639) and
      upstream kinases, including the mammalian target of rapamycin and p70S6 kinase.
      Intravenous injection of caffeine at a physiological dose (5 mg/kg) in rats
      inhibited the phosphorylation of insulin-stimulated IRS-1 Tyr(612) and Akt
      Ser(473) in epitrochlearis muscle. Our results indicate that caffeine inhibits
      insulin signaling partly through the IKK/IRS-1 Ser(307) pathway, via a Ca(2+)-
      and AMPK-independent mechanism in skeletal muscle.

PMID- 21940848
TI  - Exercise testing and disease risk: individualized medicine without the "omics"?

PMID- 21940849
TI  - Short-term exercise preserves myocardial glutathione and decreases arrhythmias
      after thiol oxidation and ischemia in isolated rat hearts.
AB  - The purpose of this study was to determine if exercise (Ex) protects hearts from
      arrhythmias induced by glutathione oxidation or ischemia-reperfusion (I/R).
      Female Sprague-Dawley rats were divided into two experimental groups: sedentary
      controls (Sed) or short-term Ex (10 days of treadmill running). Twenty-four hours
      after the last session, hearts were excised and exposed to either perfusion with
      the thiol oxidant diamide (200 MUM) or global I/R. Ex significantly delayed the
      time to the onset of ventricular arrhythmia after irreversible diamide perfusion.
      During a shorter diamide perfusion protocol with washout, Ex significantly
      decreased the incidence of arrhythmia, as evidenced by a delayed time to the
      first observed arrhythmia, lower arrhythmia scores, and lower incidence of
      ventricular fibrillation. Ex hearts exposed to I/R (30-min ischemia/30-min
      reperfusion) also showed lower arrhythmia scores and incidence of ventricular
      fibrillation compared with Sed counterparts. Our finding that Ex protected intact
      hearts from thiol oxidation was corroborated in isolated ventricular myocytes. In
      myocytes from Ex animals, both the increase in H(2)O(2) fluorescence and
      incidence of cell death were delayed after diamide. Although there were no
      baseline differences in reduced-to-oxidized glutathione ratios (GSH/GSSG) between
      the Sed and Ex groups, GSH/GSSG was better preserved in Ex groups after diamide
      perfusion and I/R. Myocardial glutathione reductase activity was significantly
      enhanced after Ex, and this was preserved in the Ex group after diamide
      perfusion. Our results show that Ex protects the heart from arrhythmias after two
      different oxidative stressors and support the hypothesis that sustaining the
      GSH/GSSG pool stabilizes cardiac electrical function during conditions of
      oxidative stress.

PMID- 21940850
TI  - Functional contribution of P2Y1 receptors to the control of coronary blood flow.
AB  - Activation of ADP-sensitive P2Y(1) receptors has been proposed as an integral
      step in the putative "nucleotide axis" regulating coronary blood flow. However,
      the specific mechanism(s) and overall contribution of P2Y(1) receptors to the
      control of coronary blood flow have not been clearly defined. Using vertically
      integrative studies in isolated coronary arterioles and open-chest anesthetized
      dogs, we examined the hypothesis that P2Y(1) receptors induce coronary
      vasodilation via an endothelium-dependent mechanism and contribute to coronary
      pressure-flow autoregulation and/or ischemic coronary vasodilation.
      Immunohistochemistry revealed P2Y(1) receptor expression in coronary arteriolar
      endothelial and vascular smooth muscle cells. The ADP analog 2-methylthio-ADP
      induced arteriolar dilation in vitro and in vivo that was abolished by the
      selective P2Y(1) antagonist MRS-2179 and the nitric oxide synthase inhibitor N(G)
      nitro-l-arginine methyl ester. MRS-2179 did not alter baseline coronary flow in
      vivo but significantly attenuated coronary vasodilation to ATP in vitro and in
      vivo and the nonhydrolyzable ATP analog ATPgammaS in vitro. Coronary blood flow
      responses to alterations in coronary perfusion pressure (40-100 mmHg) or to a
      brief 15-s coronary artery occlusion were unaffected by MRS-2179. Our data reveal
      that P2Y(1) receptors are functionally expressed in the coronary circulation and
      that activation produces coronary vasodilation via an endothelium/nitric oxide
      dependent mechanism. Although these receptors represent a critical component of
      purinergic coronary vasodilation, our findings indicate that P2Y(1) receptor
      activation is not required for coronary pressure-flow autoregulation or reactive
      hyperemia.

PMID- 21940851
TI  - Digital infrared thermographic imaging for remote assessment of traumatic injury.
AB  - The purpose of this study was to test the hypotheses that digital infrared
      thermographic imaging (DITI) during simulated uncontrolled hemorrhage will reveal
      1) respiratory rate and 2) changes of skin temperature that track reductions of
      stroke volume. In 45 healthy volunteers (25 men and 20 women), we recorded the
      ECG, finger photoplethysmographic arterial pressure, respiratory rate (pneumobelt
      and DITI of the nose), cardiac output (inert rebreathing), and skin temperature
      of the forehead during lower body negative pressure (LBNP) at three continuous
      decompression rates; slow (-3 mmHg/min), medium (-6 mmHg/min), and fast (-12
      mmHg/min) to an ending pressure of -60 mmHg. Respiratory rates calculated from
      the pneumobelt (14.7 +/- 0.9 breaths/min) and DITI (14.9 +/- 1.2 breaths/min)
      were not different (P = 0.21). LBNP induced an average stroke volume reduction of
      1.3 ml/mmHg regardless of decompression speed. Maximal reductions of stroke
      volume and forehead temperature were -100 +/- 12 ml and -0.32 +/- 0.12 degrees C
      (slow), -86 +/- 12 ml and -0.74 +/- 0.27 degrees C (medium), and -78 +/- 5 ml and
      -0.17 +/- 0.02 degrees C (fast). Changes of forehead temperature as a function of
      changes of stroke volume were best described by a quadratic fit to the data (slow
      R(2) = 0.95; medium R(2) = 0.89; and fast R(2) = 0.99).Our results suggest that a
      thermographic camera may prove useful for the remote assessment of traumatically
      injured patients. Life sign detection may be determined by verifying respiratory
      rate. Determining the magnitude and rate of hemorrhage may also be possible based
      on future algorithms derived from associations between skin temperature and
      stroke volume.

PMID- 21940852
TI  - Effect of cold air inhalation and isometric exercise on coronary blood flow and
      myocardial function in humans.
AB  - The effects of cold air inhalation and isometric exercise on coronary blood flow
      are currently unknown, despite the fact that both cold air and acute exertion
      trigger angina in clinical populations. In this study, we used transthoracic
      Doppler echocardiography to measure coronary blood flow velocity (CBV; left
      anterior descending coronary artery) and myocardial function during cold air
      inhalation and handgrip exercise. Ten young healthy subjects underwent the
      following protocols: 5 min of inhaling cold air (cold air protocol), 5 min of
      inhaling thermoneutral air (sham protocol), 2 min of isometric handgrip at 30% of
      maximal voluntary contraction (grip protocol), and 5 min of isometric handgrip at
      30% maximal voluntary contraction while breathing cold air (cold + grip
      protocol). Heart rate, blood pressure, inspired air temperature, CBV, myocardial
      function (tissue Doppler imaging), O(2) saturation, and pulmonary function were
      measured. The rate-pressure product (RPP) was used as an index of myocardial O(2)
      demand, whereas CBV was used as an index of myocardial O(2) supply. Compared with
      the sham protocol, the cold air protocol caused a significantly higher RPP, but
      there was a significant reduction in CBV. The cold + grip protocol caused a
      significantly greater increase in RPP compared with the grip protocol (P =
      0.045), but the increase in CBV was significantly less (P = 0.039). However,
      myocardial function was not impaired during the cold + grip protocol relative to
      the grip protocol alone. Collectively, these data indicate that there is a supply
      demand mismatch in the coronary vascular bed when cold ambient air is breathed
      during acute exertion but myocardial function is preserved, suggesting an
      adequate redistribution of blood flow.

PMID- 21940854
TI  - Our flaws are more human than yours: ingroup bias in humanizing negative
      characteristics.
AB  - Four studies investigated whether people tend to see ingroup flaws as part of
      human nature (HN) to a greater degree than outgroup flaws. In Study 1, people
      preferentially ascribed high HN flaws to their ingroup relative to two outgroups.
      Study 2 demonstrated that flaws were rated higher on HN when attributed to the
      ingroup than when attributed to an outgroup, and no such difference occurred for
      positive traits. Study 3 replicated this humanizing ingroup flaws (HIF) effect
      and showed that it was (a) independent of desirability and (b) specific to the HN
      sense of humanness. Study 4 replicated the results of Study 3 and demonstrated
      that the HIF effect is amplified under ingroup identity threat. Together, these
      findings show that people humanize ingroup flaws and preferentially ascribe high
      HN flaws to the ingroup. These ingroup humanizing biases may serve a group
      protective function by mitigating ingroup flaws as "only human."

PMID- 21940853
TI  - Regional function-structure relationships in lungs of an elastase murine model of
      emphysema.
AB  - Changes in lung function and structure were studied using hyperpolarized (3)He
      MRI in an elastase-induced murine model of emphysema. The combined analysis of
      the apparent diffusion coefficient (ADC) and fractional ventilation (R) were used
      to distinguish emphysematous changes and also to develop a model for classifying
      sections of the lung into diseased and normal. Twelve healthy male BALB/c mice
      (26 +/- 2 g) were randomized into healthy and elastase-induced mice and studied
      ~8-11 wk after model induction. ADC and R were measured at a submillimeter planar
      resolution. Chord length (L(x)) data were analyzed from histology samples from
      the corresponding imaged slices. Logistic regression was applied to estimate the
      probability that an imaged pixel came from a diseased animal, and bootstrap
      methods (1,000 samples) were used to compare the regression results for the
      morphological and imaging results. Multivariate ANOVA (MANOVA) was used to
      analyze transformed ADC (ADC(BC)), and R (R(BC)) data and also to control for the
      experiment-wide error rate. MANOVA and ANOVA showed that elastase induced a
      statistically measureable change in the average transformed L(x) and ADC(BC) but
      not in the average R(BC). Marginal mean analysis demonstrated that ADC(BC) was on
      average 0.19 [95% confidence interval (CI): 0.16, 0.22] higher in the emphysema
      group, whereas R(BC) was on average 0.05 (95% CI: 0.04, 0.06) lower. Logistic
      regression supported the hypothesis that ADC(BC) and R(BC), together, were better
      at differentiating normal from diseased tissue than either measurement alone. The
      odds ratios for ADC(BC) and R(BC) were 7.73 (95% CI: 5.23, 11.42) and 9.14 * 10(
      5) (95% CI: 3.33 * 10(-5), 25.06 * 10(-5)), respectively. Using a 50% probability
      cutoff, this model classified 70.6% of pixels correctly. The sensitivity and
      specificity of this model at the 50% cutoff were 74.9% and 65.2%, respectively.
      The area under the receiver operating characteristic curve was 0.76 (95% CI:
      0.74, 0.78). The regression model presented can be used to map MRI data to
      disease probability maps. These probability maps present a future possibility of
      using both measurements in a more clinically feasible method of diagnosing this
      disease.

PMID- 21940855
TI  - Reproduction of cultural values: a cross-cultural examination of stories people
      create and transmit.
AB  - Narratives are one of the oldest and universal forms of communication in human
      societies. In the present research, the authors hypothesized that narratives play
      an important role in the reproduction of cultural values. To test this idea,
      Study 1 examined the contents of stories created by American and Japanese
      participants for their reflection of individualistic and collectivistic values,
      and Study 2 examined whether information consistent with cultural values would be
      more likely to be retained and passed onto others. The studies found that
      American participants created stories that reflected individualistic values and
      retained more individualistic information than collectivistic information when
      they transmitted a story to others. In contrast, Japanese participants created
      stories that reflected collectivistic values and retained more collectivistic
      information than individualistic information when they transmitted a story to
      others. These findings support the idea that narrative communication is an
      important part of cultural reproduction mechanism.

PMID- 21940856
TI  - An Aboriginal Australian genome reveals separate human dispersals into Asia.
AB  - We present an Aboriginal Australian genomic sequence obtained from a 100-year-old
      lock of hair donated by an Aboriginal man from southern Western Australia in the
      early 20th century. We detect no evidence of European admixture and estimate
      contamination levels to be below 0.5%. We show that Aboriginal Australians are
      descendants of an early human dispersal into eastern Asia, possibly 62,000 to
      75,000 years ago. This dispersal is separate from the one that gave rise to
      modern Asians 25,000 to 38,000 years ago. We also find evidence of gene flow
      between populations of the two dispersal waves prior to the divergence of Native
      Americans from modern Asian ancestors. Our findings support the hypothesis that
      present-day Aboriginal Australians descend from the earliest humans to occupy
      Australia, likely representing one of the oldest continuous populations outside
      Africa.

PMID- 21940857
TI  - N-terminal acetylation acts as an avidity enhancer within an interconnected
      multiprotein complex.
AB  - Although many eukaryotic proteins are amino (N)-terminally acetylated, structural
      mechanisms by which N-terminal acetylation mediates protein interactions are
      largely unknown. Here, we found that N-terminal acetylation of the E2 enzyme,
      Ubc12, dictates distinctive E3-dependent ligation of the ubiquitin-like protein
      Nedd8 to Cul1. Structural, biochemical, biophysical, and genetic analyses
      revealed how complete burial of Ubc12's N-acetyl-methionine in a hydrophobic
      pocket in the E3, Dcn1, promotes cullin neddylation. The results suggest that the
      N-terminal acetyl both directs Ubc12's interactions with Dcn1 and prevents
      repulsion of a charged N terminus. Our data provide a link between acetylation
      and ubiquitin-like protein conjugation and define a mechanism for N-terminal
      acetylation-dependent recognition.

PMID- 21940858
TI  - Replication-dependent loss of 5-hydroxymethylcytosine in mouse preimplantation
      embryos.
AB  - Although global erasure of DNA methylation has been observed in zygotes and
      primordial germ cells, the responsible enzyme(s) have been elusive. The
      demonstration that members of the Tet (ten eleven translocation) family of
      proteins are capable of catalyzing conversion of 5-methylcytosine (5mC) of DNA to
      5-hydroxymethylcytosine (5hmC) raises the possibility that Tet proteins may
      participate in this process. Indeed, recent studies have implicated the
      involvement of Tet3 in the conversion of 5mC to 5hmC in zygotes. This result,
      combined with the demonstration that Tet proteins can further oxidize 5hmC to 5
      carboxylcytosine followed by excision by thymine-DNA glycosylase, raises the
      possibility that active demethylation may take place in a process that involves
      Tet3-mediated oxidation followed by base excision repair. We demonstrated by
      immunostaining of mitotic chromosome spreads of preimplantation embryos that the
      5hmC associated with the paternal genome in zygotes is gradually lost during
      preimplantation development. Our study suggests that, although the conversion of
      5mC to 5hmC in zygotes is an enzyme-catalyzed process, loss of 5hmC during
      preimplantation appears to be a DNA replication-dependent passive process.

PMID- 21940860
TI  - Increasing N abundance in the northwestern Pacific Ocean due to atmospheric
      nitrogen deposition.
AB  - The relative abundance of nitrate (N) over phosphorus (P) has increased over the
      period since 1980 in the marginal seas bordering the northwestern Pacific Ocean,
      located downstream of the populated and industrialized Asian continent. The
      increase in N availability within the study area was mainly driven by increasing
      N concentrations and was most likely due to deposition of pollutant nitrogen from
      atmospheric sources. Atmospheric nitrogen deposition had a high temporal
      correlation with N availability in the study area (r = 0.74 to 0.88), except in
      selected areas wherein riverine nitrogen load may be of equal importance. The
      increase in N availability caused by atmospheric deposition and riverine input
      has switched extensive parts of the study area from being N-limited to P-limited.

PMID- 21940868
TI  - High-energy physics. The Tevatron's epitaph: solid science, no surprises.

PMID- 21940863
TI  - Rethinking clinical trials.

PMID- 21940869
TI  - Exoplanets. Star measurements hint at many more abodes for life.

PMID- 21940862
TI  - Failure to confirm XMRV/MLVs in the blood of patients with chronic fatigue
      syndrome: a multi-laboratory study.
AB  - Murine leukemia viruses (MLVs), including xenotropic-MLV-related virus (XMRV),
      have been controversially linked to chronic fatigue syndrome (CFS). To explore
      this issue in greater depth, we compiled coded replicate samples of blood from 15
      subjects previously reported to be XMRV/MLV-positive (14 with CFS) and from 15
      healthy donors previously determined to be negative for the viruses. These
      samples were distributed in a blinded fashion to nine laboratories, which
      performed assays designed to detect XMRV/MLV nucleic acid, virus replication, and
      antibody. Only two laboratories reported evidence of XMRV/MLVs; however,
      replicate sample results showed disagreement, and reactivity was similar among
      CFS subjects and negative controls. These results indicate that current assays do
      not reproducibly detect XMRV/MLV in blood samples and that blood donor screening
      is not warranted.

PMID- 21940871
TI  - Astronomy. Webb telescope pulled back from the brink--for now.

PMID- 21940870
TI  - Human evolution. Aboriginal genome shows two-wave settlement of Asia.

PMID- 21940872
TI  - Human evolution. Tracing the paths of the first Americans.

PMID- 21940873
TI  - Plant biology. Banking seeds for future evolutionary scientists.

PMID- 21940874
TI  - Virology. False positive.

PMID- 21940861
TI  - Impacts of the Cretaceous Terrestrial Revolution and KPg extinction on mammal
      diversification.
AB  - Previous analyses of relations, divergence times, and diversification patterns
      among extant mammalian families have relied on supertree methods and local
      molecular clocks. We constructed a molecular supermatrix for mammalian families
      and analyzed these data with likelihood-based methods and relaxed molecular
      clocks. Phylogenetic analyses resulted in a robust phylogeny with better
      resolution than phylogenies from supertree methods. Relaxed clock analyses
      support the long-fuse model of diversification and highlight the importance of
      including multiple fossil calibrations that are spread across the tree. Molecular
      time trees and diversification analyses suggest important roles for the
      Cretaceous Terrestrial Revolution and Cretaceous-Paleogene (KPg) mass extinction
      in opening up ecospace that promoted interordinal and intraordinal
      diversification, respectively. By contrast, diversification analyses provide no
      support for the hypothesis concerning the delayed rise of present-day mammals
      during the Eocene Period.

PMID- 21940875
TI  - Revolutionize Egypt's science culture.

PMID- 21940876
TI  - Breathing life into mortality data collection.

PMID- 21940878
TI  - Decentralize Egypt's higher education.

PMID- 21940879
TI  - Education. The pseudoscience of single-sex schooling.

PMID- 21940880
TI  - Development. The sperm's sweet tooth.

PMID- 21940881
TI  - Ecology. Biodiversity and productivity.

PMID- 21940882
TI  - Ecology. Coexisting with cattle.

PMID- 21940883
TI  - Astronomy. A black widow's best friend?

PMID- 21940885
TI  - Chemistry. Ironing out hydrogen storage.

PMID- 21940884
TI  - Microbiology. Antibiotic resistance, not shaken or stirred.

PMID- 21940886
TI  - Materials science. Generating helices in nature.

PMID- 21940887
TI  - Electrically controlled nonlinear generation of light with plasmonics.
AB  - Plasmonics provides a route to develop ultracompact optical devices on a chip by
      using extreme light concentration and the ability to perform simultaneous
      electrical and optical functions. These properties also make plasmonics an ideal
      candidate for dynamically controlling nonlinear optical interactions at the
      nanoscale. We demonstrate electrically tunable harmonic generation of light from
      a plasmonic nanocavity filled with a nonlinear medium. The metals that define the
      cavity also serve as electrodes that can generate high direct current electric
      fields across the nonlinear material. A fundamental wave at 1.56 micrometers was
      frequency doubled and modulated in intensity by applying a moderate external
      voltage to the electrodes, yielding a voltage-dependent nonlinear generation with
      a normalized magnitude of ~7% per volt.

PMID- 21940888
TI  - Geometry and mechanics in the opening of chiral seed pods.
AB  - We studied the mechanical process of seed pods opening in Bauhinia variegate and
      found a chirality-creating mechanism, which turns an initially flat pod valve
      into a helix. We studied configurations of strips cut from pod valve tissue and
      from composite elastic materials that mimic its structure. The experiments reveal
      various helical configurations with sharp morphological transitions between them.
      Using the mathematical framework of "incompatible elasticity," we modeled the pod
      as a thin strip with a flat intrinsic metric and a saddle-like intrinsic
      curvature. Our theoretical analysis quantitatively predicts all observed
      configurations, thus linking the pod's microscopic structure and macroscopic
      conformation. We suggest that this type of incompatible strip is likely to play a
      role in the self-assembly of chiral macromolecules and could be used for the
      engineering of synthetic self-shaping devices.

PMID- 21940889
TI  - The role of a bilayer interfacial phase on liquid metal embrittlement.
AB  - Intrinsically ductile metals are prone to catastrophic failure when exposed to
      certain liquid metals, but the atomic-level mechanism for this effect is not
      fully understood. We characterized a model system, a nickel sample infused with
      bismuth atoms, by using aberration-corrected scanning transmission electron
      microscopy and observed a bilayer interfacial phase that is the underlying cause
      of embrittlement. This finding provides a new perspective for understanding the
      atomic-scale embrittlement mechanism and for developing strategies to control the
      practically important liquid metal embrittlement and the more general grain
      boundary embrittlement phenomena in alloys. This study further demonstrates that
      adsorption can induce a coupled grain boundary structural and chemical phase
      transition that causes drastic changes in properties.

PMID- 21940890
TI  - Efficient dehydrogenation of formic acid using an iron catalyst.
AB  - Hydrogen is one of the essential reactants in the chemical industry, though its
      generation from renewable sources and storage in a safe and reversible manner
      remain challenging. Formic acid (HCO(2)H or FA) is a promising source and storage
      material in this respect. Here, we present a highly active iron catalyst system
      for the liberation of H(2) from FA. Applying 0.005 mole percent of
      Fe(BF(4))(2).6H(2)O and tris[(2-diphenylphosphino)ethyl]phosphine
      [P(CH(2)CH(2)PPh(2))(3), PP(3)] to a solution of FA in environmentally benign
      propylene carbonate, with no further additives or base, affords turnover
      frequencies up to 9425 per hour and a turnover number of more than 92,000 at 80
      degrees C. We used in situ nuclear magnetic resonance spectroscopy, kinetic
      studies, and density functional theory calculations to explain possible reaction
      mechanisms.

PMID- 21940891
TI  - Megacity emissions and lifetimes of nitrogen oxides probed from space.
AB  - Megacities are immense sources of air pollutants, with large impacts on air
      quality and climate. However, emission inventories in many of them still are
      highly uncertain, particularly in developing countries. Satellite observations
      allow top-down estimates of emissions to be made for nitrogen oxides (NO(x) = NO
      + NO(2)), but require poorly quantified a priori information on the NO(x)
      lifetime. We present a method for the simultaneous determination of megacity
      NO(x) emissions and lifetimes from satellite measurements by analyzing the
      downwind patterns of NO(2) separately for different wind conditions. Daytime
      lifetimes are ~4 hours at low and mid-latitudes, but ~8 hours in wintertime for
      Moscow. The derived NO(x) emissions are generally in good agreement with existing
      emission inventories, but are higher by a factor of 3 for the Saudi Arabian
      capital Riyadh.

PMID- 21940892
TI  - Inbreeding promotes female promiscuity.
AB  - The widespread phenomenon of polyandry (mating by females with multiple males) is
      an evolutionary puzzle, because females can sustain costs from promiscuity,
      whereas full fertility can be provided by a single male. Using the red flour
      beetle, Tribolium castaneum, we identify major fitness benefits of polyandry to
      females under inbreeding, when the risks of fertilization by incompatible male
      haplotypes are especially high. Fifteen generations after inbred populations had
      passed through genetic bottlenecks, we recorded increased levels of female
      promiscuity compared with noninbred controls, most likely due to selection from
      prospective fitness gains through polyandry. These data illustrate how this
      common mating pattern can evolve if population genetic bottlenecks increase the
      risks of fitness depression due to fertilization by sperm carrying genetically
      incompatible haplotypes.

PMID- 21940894
TI  - Single-base pair unwinding and asynchronous RNA release by the hepatitis C virus
      NS3 helicase.
AB  - Nonhexameric helicases use adenosine triphosphate (ATP) to unzip base pairs in
      double-stranded nucleic acids (dsNAs). Studies have suggested that these
      helicases unzip dsNAs in single-base pair increments, consuming one ATP molecule
      per base pair, but direct evidence for this mechanism is lacking. We used optical
      tweezers to follow the unwinding of double-stranded RNA by the hepatitis C virus
      NS3 helicase. Single-base pair steps by NS3 were observed, along with nascent
      nucleotide release that was asynchronous with base pair opening. Asynchronous
      release of nascent nucleotides rationalizes various observations of its dsNA
      unwinding and may be used to coordinate the translocation speed of NS3 along the
      RNA during viral replication.

PMID- 21940895
TI  - Productivity is a poor predictor of plant species richness.
AB  - For more than 30 years, the relationship between net primary productivity and
      species richness has generated intense debate in ecology about the processes
      regulating local diversity. The original view, which is still widely accepted,
      holds that the relationship is hump-shaped, with richness first rising and then
      declining with increasing productivity. Although recent meta-analyses questioned
      the generality of hump-shaped patterns, these syntheses have been criticized for
      failing to account for methodological differences among studies. We addressed
      such concerns by conducting standardized sampling in 48 herbaceous-dominated
      plant communities on five continents. We found no clear relationship between
      productivity and fine-scale (meters(-2)) richness within sites, within regions,
      or across the globe. Ecologists should focus on fresh, mechanistic approaches to
      understanding the multivariate links between productivity and richness.

PMID- 21940896
TI  - African wild ungulates compete with or facilitate cattle depending on season.
AB  - Savannas worldwide are vital for both socioeconomic and biodiversity values. In
      these ecosystems, management decisions are based on the perception that wildlife
      and livestock compete for food, yet there are virtually no experimental data to
      support this assumption. We examined the effects of wild African ungulates on
      cattle performance, food intake, and diet quality. Wild ungulates depressed
      cattle food intake and performance during the dry season (competition) but
      enhanced cattle diet quality and performance during the wet season
      (facilitation). These results extend our understanding of the context-dependent
      competition-facilitation balance, in general, and are critical for better
      understanding and managing wildlife-livestock coexistence in human-occupied
      savanna landscapes.

PMID- 21940893
TI  - Asynchronous diversification in a specialized plant-pollinator mutualism.
AB  - Most flowering plants establish mutualistic associations with insect pollinators
      to facilitate sexual reproduction. However, the evolutionary processes that gave
      rise to these associations remain poorly understood. We reconstructed the times
      of divergence, diversification patterns, and interaction networks of a diverse
      group of specialized orchids and their bee pollinators. In contrast to a scenario
      of coevolution by race formation, we show that fragrance-producing orchids
      originated at least three times independently after their fragrance-collecting
      bee mutualists. Whereas orchid diversification has apparently tracked the
      diversification of orchids' bee pollinators, bees appear to have depended on the
      diverse chemical environment of neotropical forests. We corroborated this
      apparent asymmetrical dependency by simulating co-extinction cascades in real
      interaction networks that lacked reciprocal specialization. These results suggest
      that the diversification of insect-pollinated angiosperms may have been
      facilitated by the exploitation of preexisting sensory biases of insect
      pollinators.

PMID- 21940897
TI  - Disentangling the drivers of beta diversity along latitudinal and elevational
      gradients.
AB  - Understanding spatial variation in biodiversity along environmental gradients is
      a central theme in ecology. Differences in species compositional turnover among
      sites (beta diversity) occurring along gradients are often used to infer
      variation in the processes structuring communities. Here, we show that sampling
      alone predicts changes in beta diversity caused simply by changes in the sizes of
      species pools. For example, forest inventories sampled along latitudinal and
      elevational gradients show the well-documented pattern that beta diversity is
      higher in the tropics and at low elevations. However, after correcting for
      variation in pooled species richness (gamma diversity), these differences in beta
      diversity disappear. Therefore, there is no need to invoke differences in the
      mechanisms of community assembly in temperate versus tropical systems to explain
      these global-scale patterns of beta diversity.

PMID- 21940898
TI  - A role for Snf2-related nucleosome-spacing enzymes in genome-wide nucleosome
      organization.
AB  - The positioning of nucleosomes within the coding regions of eukaryotic genes is
      aligned with respect to transcriptional start sites. This organization is likely
      to influence many genetic processes, requiring access to the underlying DNA.
      Here, we show that the combined action of Isw1 and Chd1 nucleosome-spacing
      enzymes is required to maintain this organization. In the absence of these
      enzymes, regular positioning of the majority of nucleosomes is lost. Exceptions
      include the region upstream of the promoter, the +1 nucleosome, and a subset of
      locations distributed throughout coding regions where other factors are likely to
      be involved. These observations indicate that adenosine triphosphate-dependent
      remodeling enzymes are responsible for directing the positioning of the majority
      of nucleosomes within the Saccharomyces cerevisiae genome.

PMID- 21940899
TI  - Acceleration of emergence of bacterial antibiotic resistance in connected
      microenvironments.
AB  - The emergence of bacterial antibiotic resistance is a growing problem, yet the
      variables that influence the rate of emergence of resistance are not well
      understood. In a microfluidic device designed to mimic naturally occurring
      bacterial niches, resistance of Escherichia coli to the antibiotic ciprofloxacin
      developed within 10 hours. Resistance emerged with as few as 100 bacteria in the
      initial inoculation. Whole-genome sequencing of the resistant organisms revealed
      that four functional single-nucleotide polymorphisms attained fixation. Knowledge
      about the rapid emergence of antibiotic resistance in the heterogeneous
      conditions within the mammalian body may be helpful in understanding the
      emergence of drug resistance during cancer chemotherapy.

PMID- 21940900
TI  - Immunomodulatory action of dietary fish oil and targeted deletion of intestinal
      epithelial cell PPARdelta in inflammation-induced colon carcinogenesis.
AB  - The ligand-activated transcription factor peroxisome proliferator-activated
      receptor (PPAR)-delta is highly expressed in colonic epithelial cells; however,
      the role of PPARdelta ligands, such as fatty acids, in mucosal inflammation and
      malignant transformation has not been clarified. Recent evidence suggests that
      the anti-inflammatory/chemoprotective properties of fish oil (FO)-derived n-3
      polyunsaturated fatty acids (PUFAs) may be partly mediated by PPARdelta.
      Therefore, we assessed the role of PPARdelta in modulating the effects of dietary
      n-3 PUFAs by targeted deletion of intestinal epithelial cell PPARdelta
      (PPARdelta(DeltaIEpC)). Subsequently, we documented changes in colon
      tumorigenesis and the inflammatory microenvironment, i.e., local [mesenteric
      lymph node (MLN)] and systemic (spleen) T cell activation. Animals were fed
      chemopromotive [corn oil (CO)] or chemoprotective (FO) diets during the induction
      of chronic inflammation/carcinogenesis. Tumor incidence was similar in control
      and PPARdelta(DeltaIEpC) mice. FO reduced mucosal injury, tumor incidence,
      colonic STAT3 activation, and inflammatory cytokine gene expression, independent
      of PPARdelta genotype. CD8(+) T cell recruitment into MLNs was suppressed in
      PPARdelta(DeltaIEpC) mice. Similarly, FO reduced CD8(+) T cell numbers in the
      MLN. Dietary FO independently modulated MLN CD4(+) T cell activation status by
      decreasing CD44 expression. CD11a expression by MLN CD4(+) T cells was
      downregulated in PPARdelta(DeltaIEpC) mice. Lastly, splenic CD62L expression was
      downregulated in PPARdelta(DeltaIEpC) CD4(+) and CD8(+) T cells. These data
      demonstrate that expression of intestinal epithelial cell PPARdelta does not
      influence azoxymethane/dextran sodium sulfate-induced colon tumor incidence.
      Moreover, we provide new evidence that dietary n-3 PUFAs attenuate intestinal
      inflammation in an intestinal epithelial cell PPARdelta-independent manner.

PMID- 21940901
TI  - Ano1 as a regulator of proliferation.
AB  - Ano1 is a recently discovered Ca(2+)-activated Cl(-) channel expressed on
      interstitial cells of Cajal (ICC) that has been implicated in slow-wave activity
      in the gut. However, Ano1 is expressed on all classes of ICC, even those that do
      not contribute to generation of the slow wave, suggesting that Ano1 may have an
      alternate function in these cells. Ano1 is also highly expressed in
      gastrointestinal stromal tumors. Mice lacking Ano1 had fewer proliferating ICC in
      whole mount preparations and in culture, raising the possibility that Ano1 is
      involved in proliferation. Cl(-) channel blockers decreased proliferation in
      cells expressing Ano1, including primary cultures of ICC and in the pancreatic
      cancer-derived cell line, CFPAC-1. Cl(-) channel blockers had a reduced effect on
      Ano1(-/-) cultures, confirming that the blockers are acting on Ano1. Ki67
      immunoreactivity, 5-ethynyl-2'-deoxyuridine incorporation, and cell-cycle
      analysis of cells grown in low-Cl(-) media showed fewer proliferating cells than
      in cultures grown in regular medium. We confirmed that mice lacking Ano1 had less
      phosphorylated retinoblastoma protein compared with controls. These data led us
      to conclude that Ano1 regulates proliferation at the G(1)/S transition of the
      cell cycle and may play a role in tumorigenesis.

PMID- 21940902
TI  - Linkage of gut microbiome with cognition in hepatic encephalopathy.
AB  - Hepatic encephalopathy (HE) has been related to gut bacteria and inflammation in
      the setting of intestinal barrier dysfunction. We aimed to link the gut
      microbiome with cognition and inflammation in HE using a systems biology
      approach. Multitag pyrosequencing (MTPS) was performed on stool of cirrhotics and
      age-matched controls. Cirrhotics with/without HE underwent cognitive testing,
      inflammatory cytokines, and endotoxin analysis. Patients with HE were compared
      with those without HE using a correlation-network analysis. A select group of
      patients with HE (n = 7) on lactulose underwent stool MTPS before and after
      lactulose withdrawal over 14 days. Twenty-five patients [17 HE (all on lactulose,
      6 also on rifaximin) and 8 without HE, age 56 +/- 6 yr, model for end-stage liver
      disease score 16 +/- 6] and ten controls were included. Fecal microbiota in
      cirrhotics were significantly different (higher Enterobacteriaceae,
      Alcaligeneceae, and Fusobacteriaceae and lower Ruminococcaceae and
      Lachnospiraceae) compared with controls. We found altered flora (higher
      Veillonellaceae), poor cognition, endotoxemia, and inflammation (IL-6, TNF-alpha,
      IL-2, and IL-13) in HE compared with cirrhotics without HE. In the cirrhosis
      group, Alcaligeneceae and Porphyromonadaceae were positively correlated with
      cognitive impairment. Fusobacteriaceae, Veillonellaceae, and Enterobacteriaceae
      were positively and Ruminococcaceae negatively related to inflammation. Network
      analysis comparison showed robust correlations (all P < 1E-5) only in the HE
      group between the microbiome, cognition, and IL-23, IL-2, and IL-13. Lactulose
      withdrawal did not change the microbiome significantly beyond Fecalibacterium
      reduction. We concluded that cirrhosis, especially when complicated with HE, is
      associated with significant alterations in the stool microbiome compared with
      healthy individuals. Specific bacterial families (Alcaligeneceae,
      Porphyromonadaceae, Enterobacteriaceae) are strongly associated with cognition
      and inflammation in HE.

PMID- 21940903
TI  - Effect of hepatic cytochrome P450 (P450) oxidoreductase deficiency on 2-amino-1
      methyl-6-phenylimidazo[4,5-b]pyridine-DNA adduct formation in P450 reductase
      conditional null mice.
AB  - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), formed during the cooking
      of foods, induces colon cancer in rodents. PhIP is metabolically activated by
      cytochromes P450 (P450s). To evaluate the role of hepatic P450s in the
      bioactivation of PhIP, we used Reductase Conditional Null (RCN) mice, in which
      cytochrome P450 oxidoreductase (POR), the unique electron donor to P450s, can be
      specifically deleted in hepatocytes by pretreatment with 3-methylcholanthrene (3
      MC), resulting in the loss of essentially all hepatic P450 function. RCN mice
      were treated orally with 50 mg/kg b.wt. PhIP daily for 5 days, with and without 3
      MC pretreatment. PhIP-DNA adducts (i.e., N-(deoxyguanosin-8-yl)-2-amino-1-methyl
      6-phenylimidazo[4,5-b]pyridine [dG-C8-PhIP]), measured by liquid chromatography
      tandem mass spectrometry, were highest in colon (1362 adducts/10(8)
      deoxynucleosides), whereas adduct levels in liver were ~3.5-fold lower. Whereas
      no differences in PhIP-DNA adduct levels were found in livers with active POR
      versus inactivated POR, adduct levels were on average ~2-fold lower in
      extrahepatic tissues of mice lacking hepatic POR. Hepatic microsomes from RCN
      mice with or without 3-MC pretreatment were also incubated with PhIP and DNA in
      vitro. PhIP-DNA adduct formation was ~8-fold lower with hepatic microsomes from
      POR-inactivated mice than with those with active POR. Most of the hepatic
      microsomal activation of PhIP in vitro was attributable to CYP1A. Our results
      show that PhIP-DNA adduct formation in colon involves hepatic N-oxidation,
      circulation of activated metabolites via the bloodstream to extrahepatic tissues,
      and further activation, resulting in the formation of dG-C8-PhIP. Besides hepatic
      P450s, PhIP may be metabolically activated mainly by a non-P450 pathway in liver.

PMID- 21940904
TI  - Analysis and prediction of drug transfer into human milk taking into
      consideration secretion and reuptake clearances across the mammary epithelia.
AB  - Medication use during lactation is a matter of concern due to unnecessary
      exposure of infants to drugs. Although some studies have predicted the extent of
      drug transfer into milk from physicochemical parameters, drug concentration-time
      profiles in milk have not been predicted or even analyzed yet. In the present
      study, a drug transfer model was constructed by defining secretion and reuptake
      clearances (CL(sec) and CL(re), respectively) between milk and plasma based on
      unbound drug concentrations. Through the use of this model, drug concentration
      time profiles were analyzed in human milk and plasma based on data collected from
      the literature. CL(sec) and CL(re) values were obtained successfully for 49
      drugs. Because the CL(sec) and CL(re) values were in general similar for each
      drug, transport across the mammary epithelia was mediated by passive diffusion in
      most cases. This study demonstrated that the logarithmically transformed values
      of CL(sec) and CL(re) can be predicted from physicochemical parameters with
      adjusted R(2) values of 0.705 and 0.472, respectively. Moreover, 66.7 and 77.8%
      of predicted CL(sec) and CL(re) values were within 3-fold error ranges of the
      observed values for 45 and 27 drugs, respectively. Finally, time profiles of drug
      concentrations in milk were simulated from physicochemical parameters. The milk
      to-plasma area under the concentration-time curve ratios also were predicted
      successfully within 3-fold error ranges of the observed values for 71.9% of the
      drugs analyzed. The method described herein therefore may be useful in predicting
      drug concentration-time profiles in human milk for newly developed drugs.

PMID- 21940905
TI  - Inhibition of human liver aldehyde oxidase: implications for potential drug-drug
      interactions.
AB  - During the course of our research efforts to understand the kinetics of human
      aldehyde oxidase as a xenobiotic-clearing enzyme, we investigated the effect of
      eight different inhibitors on the oxidation of the probe substrate phthalazine.
      Saturation kinetic parameters for phthalazine oxidation in human liver cytosol
      were found to be the following: K(m) = 8.0 +/- 0.4 MUM and V(max) = 4.3 +/- 0.1
      nmol . min(-1) . mg protein(-1). Inhibitory potency of the inhibitors tested
      ranged from 0.1 to 5 MUM. Of the eight different inhibitor compounds tested,
      seven were observed to inhibit through a mixed mode and one through a strictly
      competitive mode. A ratio of the K(ii) and K(is) values was used to assess the
      relative competitiveness of each inhibitor. For the mixed inhibitors, the mode of
      inhibition varied from mostly uncompetitive to predominantly competitive
      (K(ii)/K(is) values ranging from 0.1 to 15). The implications for potential drug
      drug interactions and inhibition mechanism are discussed. We found two
      inhibitors, clozapine and chlorpromazine, that have a moderate predicted risk of
      drug-drug interactions based on the K(i) value relative to the inhibitor
      concentration in human plasma, having a calculated [I]/K(i) value of 0.4 and 0.8,
      respectively.

PMID- 21940906
TI  - Hepatic uptake in the dog: comparison of uptake in hepatocytes and human
      embryonic kidney cells expressing dog organic anion-transporting polypeptide 1B4.
AB  - Although the dog is frequently used in pharmacological, pharmacokinetic, and drug
      safety studies, little is known about canine drug transporters. Dog organic anion
      transporting polypeptide (Oatp1b4) has recently been cloned (Comp Biochem Physiol
      C Toxicol Pharmacol 151:393-399, 2010), but the contribution of Oatp1b4 to
      hepatic uptake has yet to be clarified. This study compares the transport
      characteristics of dog Oatp1b4 with those of human OATP1B1/1B3 and demonstrates
      the importance of Oatp1b4 in the uptake of anionic compounds in dog hepatocytes.
      Oatp1b4 is the predominant Oatp in dog liver with expression levels double and 30
      times those of Oatp2b1 and Oatp1a2, respectively. Uptake of a range of typical
      OATP substrates by Oatp1b4-expressing HEK293 cells was compared with that in
      fresh dog hepatocytes. All compounds tested were transported by Oatp1b4 and
      uptake intrinsic clearance (CL(int, uptake)) in dog hepatocytes in sodium-free
      buffer was correlated significantly with CL(int, uptake) in Oatp1b4-expressing
      cells. Dog in vivo clearance for five substrates was predicted more accurately
      from CL(int, uptake) than from metabolic intrinsic clearance (CL(int, met)),
      indicating that uptake governs the overall in vivo hepatic clearance of these
      anionic compounds in dog. The substrate specificities of dog Oatp1b4 appear to be
      similar to those of human OATP1B1/OATP1B3, whereas the relative uptake clearance
      of substrates for Oatp1b4 correlate better with OATP1B3 than with the more
      abundant hepatic analog OATP1B1.

PMID- 21940907
TI  - Joint effects of alcohol consumption and polymorphisms in alcohol and oxidative
      stress metabolism genes on risk of head and neck cancer.
AB  - BACKGROUND: Single-nucleotide polymorphisms (SNP) in alcohol metabolism genes are
      associated with squamous cell carcinoma of the head and neck (SCCHN) and may
      influence cancer risk in conjunction with alcohol. Genetic variation in the
      oxidative stress pathway may impact the carcinogenic effect of reactive oxygen
      species produced by ethanol metabolism. We hypothesized that alcohol interacts
      with these pathways to affect SCCHN incidence. METHODS: Interview and genotyping
      data for 64 SNPs were obtained from 2,552 European- and African-American subjects
      (1,227 cases and 1,325 controls) from the Carolina Head and Neck Cancer
      Epidemiology Study, a population-based case-control study of SCCHN conducted in
      North Carolina from 2002 to 2006. We estimated ORs and 95% confidence intervals
      (CI) for SNPs and haplotypes, adjusting for age, sex, race, and duration of
      cigarette smoking. P values were adjusted for multiple testing using Bonferroni
      correction. RESULTS: Two SNPs were associated with SCCHN risk: ADH1B rs1229984 A
      allele (OR = 0.7; 95% CI, 0.6-0.9) and ALDH2 rs2238151 C allele (OR = 1.2; 95%
      CI, 1.1-1.4). Three were associated with subsite tumors: ADH1B rs17028834 C
      allele (larynx, OR = 1.5; 95% CI, 1.1-2.0), SOD2 rs4342445 A allele (oral cavity,
      OR = 1.3; 95% CI, 1.1-1.6), and SOD2 rs5746134 T allele (hypopharynx, OR = 2.1;
      95% CI, 1.2-3.7). Four SNPs in alcohol metabolism genes interacted additively
      with alcohol consumption: ALDH2 rs2238151, ADH1B rs1159918, ADH7 rs1154460, and
      CYP2E1 rs2249695. No alcohol interactions were found for oxidative stress SNPs.
      CONCLUSIONS AND IMPACT: Previously unreported associations of SNPs in ALDH2,
      CYP2E1, GPX2, SOD1, and SOD2 with SCCHN and subsite tumors provide evidence that
      alterations in alcohol and oxidative stress pathways influence SCCHN
      carcinogenesis and warrant further investigation.

PMID- 21940908
TI  - Reversal of epigenetic silencing of AP-2alpha results in increased zinc uptake in
      DU-145 and LNCaP prostate cancer cells.
AB  - Zinc accumulation is lost during prostate carcinogenesis. Recent studies reveal a
      strong association between prostate cancer progression and the downregulation of
      the zinc uptake transporters hZip1 and hZip3. The aim of this work was to assess
      the involvement of epigenetic processes in the disruption of zinc uptake
      homeostasis in prostate adenocarcinoma. In this report, we demonstrate an
      increase in hZip1 and hZip3 zinc transporters' expression and zinc uptake by the
      prostate cancer cells DU-145 and LNCaP in response to 5-aza-2'-deoxycytidine.
      This effect is due to demethylation of the promoter region of the activator
      protein (AP)-2alpha protein, which is crucial for hZip1 and hZip3 genes
      expression. Loss of AP-2alpha expression in DU-145 and LNCaP prostate cancer
      cells is due to hypermethylation of its promoter region. Similarly, we found
      higher AP-2alpha promoter methylation levels in clinical samples of early-stage
      prostate adenocarcinoma when compared with adjacent non-malignant prostate
      tissue. Taken together, our findings provide a better understanding of the
      epigenetic mechanisms that are involved in the loss of AP-2alpha protein in
      prostate cancer cells which lead to decreased cellular zinc uptake-a sine qua non
      of prostate cancer development.

PMID- 21940909
TI  - Targeted mass spectrometric approach for biomarker discovery and validation with
      nonglycosylated tryptic peptides from N-linked glycoproteins in human plasma.
AB  - A simple mass spectrometric approach for the discovery and validation of
      biomarkers in human plasma was developed by targeting nonglycosylated tryptic
      peptides adjacent to glycosylation sites in an N-linked glycoprotein, one of the
      most important biomarkers for early detection, prognoses, and disease therapies.
      The discovery and validation of novel biomarkers requires complex sample
      pretreatment steps, such as depletion of highly abundant proteins, enrichment of
      desired proteins, or the development of new antibodies. The current study
      exploited the steric hindrance of glycan units in N-linked glycoproteins, which
      significantly affects the efficiency of proteolytic digestion if an enzymatically
      active amino acid is adjacent to the N-linked glycosylation site. Proteolytic
      digestion then results in quantitatively different peptide products in accordance
      with the degree of glycosylation. The effect of glycan steric hindrance on
      tryptic digestion was first demonstrated using alpha-1-acid glycoprotein (AGP) as
      a model compound versus deglycosylated alpha-1-acid glycoprotein. Second,
      nonglycosylated tryptic peptide biomarkers, which generally show much higher
      sensitivity in mass spectrometric analyses than their glycosylated counterparts,
      were quantified in human hepatocellular carcinoma plasma using a label-free
      method with no need for N-linked glycoprotein enrichment. Finally, the method was
      validated using a multiple reaction monitoring analysis, demonstrating that the
      newly discovered nonglycosylated tryptic peptide targets were present at
      different levels in normal and hepatocellular carcinoma plasmas. The area under
      the receiver operating characteristic curve generated through analyses of
      nonglycosylated tryptic peptide from vitronectin precursor protein was 0.978, the
      highest observed in a group of patients with hepatocellular carcinoma. This work
      provides a targeted means of discovering and validating nonglycosylated tryptic
      peptides as biomarkers in human plasma, without the need for complex enrichment
      processes or expensive antibody preparations.

PMID- 21940910
TI  - Public health implications of rapid hepatitis C screening with an oral swab for
      community-based organizations serving high-risk populations.
AB  - OBJECTIVES: Between April and September of 2009 we evaluated the accuracy of the
      OraQuick HCV rapid antibody test and assessed its feasibility for use by
      community-based organizations (CBOs) serving populations at high risk for HCV in
      New York City. METHODS: We compared the results of screening by OraQuick (oral
      swab) and enzyme immunoassay (EIA; blood draw). We performed ribonucleic acid
      polymerase chain reaction testing for discordant results. We also assessed
      research staff perceptions through a survey and focus group. RESULTS: Overall,
      97.5% of OraQuick and EIA results matched. Testing of discordant samples
      indicated that the rapid test was more likely than the EIA to provide a correct
      diagnosis. Research staff preferred the rapid test and identified challenges that
      would be overcome with its use. CBOs could benefit from increased testing
      capacity, and clients might benefit from more rapid access to education,
      counseling, and referrals. CONCLUSIONS: OraQuick's accuracy is comparable to the
      EIA. The oral swab rapid test could help HCV screening programs reach individuals
      unaware of their status and expand testing into nonclinical settings such as
      mobile units.

PMID- 21940911
TI  - Association between type of health insurance and elective cesarean deliveries:
      New Jersey, 2004-2007.
AB  - OBJECTIVES: I examined the relationship between insurance coverage, which may
      influence physician incentives and maternal choices, and cesarean delivery before
      labor. METHODS: I analyzed hospital discharge data for mothers without previous
      cesarean deliveries in New Jersey between 2004 and 2007, with adjustment for
      maternal age, race, marital status, and maternal, fetal, and placental
      conditions. RESULTS: Nearly 1 in 7 women (13.9%) had a cesarean delivery without
      laboring. Insurance status was strongly associated with cesarean birth. Women
      insured by Medicaid (adjusted relative risk [ARR] = 0.88; 95% confidence interval
      [CI] = 0.84, 0.91) or self-paying (ARR = 0.81; 95% CI = 0.78, 0.85) had a
      significantly lower likelihood, and women insured by BlueCross (ARR = 1.06; 95%
      CI = 1.03, 1.09) or standard commercial plans (ARR = 1.06; 95% CI = 1.02, 1.10)
      had a significantly higher likelihood of cesarean delivery than did women insured
      by commercial health maintenance organizations. These associations persisted in
      subsets restricted to lower-risk women and in qualitative sensitivity analyses
      for a hypothetical single, binary, unmeasured confounder. CONCLUSIONS: Insurance
      status has a small, independent impact on whether a woman without a previous
      cesarean delivery proceeds to labor or has a cesarean delivery without labor.

PMID- 21940912
TI  - Contribution of obesity to international differences in life expectancy.
AB  - OBJECTIVES: The United States has the highest prevalence of obesity and one of
      the lowest life expectancies among high-income countries. We investigated the
      relationship between these 2 phenomena. METHODS: We estimated the fraction of
      deaths attributable to obesity by country, age, and sex and reestimated life
      tables after removing these deaths. To allow for a possible secular decline in
      obesity risks, we employed alternative risks from a more recent period. RESULTS:
      In our baseline analysis, obesity reduced US life expectancy at age 50 years in
      2006 by 1.54 years (95% confidence interval [CI] = 1.37, 1.93) for women and by
      1.85 years (95% CI = 1.62, 2.10) for men. Removing the effects of obesity reduced
      the US shortfall by 42% (95% CI = 36, 48) for women and 67% (95% CI = 57, 76) for
      men, relative to countries with higher life expectancies. Using more recently
      recorded risk data, we estimated that differences in obesity still accounted for
      a fifth to a third of the shortfall. CONCLUSIONS: The high prevalence of obesity
      in the United States contributes substantially to its poor international ranking
      in longevity.

PMID- 21940913
TI  - National trends in mental health disability, 1997-2009.
AB  - OBJECTIVES: I assessed recent trends in mental health disability in the US
      nonelderly adult population in the context of trends in physical disabilities and
      psychological distress. METHODS: Using data for 312 364 adults aged 18 to 64
      years from the US National Health Interview Survey, 1997 to 2009, I examined time
      trends in self-reported disability attributed to mental health conditions,
      disability attributed to other chronic problems, and significant psychological
      distress (measured by using the K6 instrument). RESULTS: The prevalence of self
      reported mental health disability increased from 2.0% of the nonelderly adult
      population in the first 3 years (1997 to 1999) to 2.7% in the last 3 years (2007
      to 2009), corresponding to an increase of almost 2 million disabled adults.
      Disability attributed to other chronic conditions decreased and significant
      psychological distress did not change appreciably. Change in self-reported mental
      health disability was more pronounced in adults who also reported disability
      attributed to other chronic conditions or significant psychological distress but
      who had no mental health contacts in the past year. CONCLUSIONS: These findings
      highlight the need for improved access to mental health services in the community
      and for better integration of these services with primary care.

PMID- 21940914
TI  - Effectiveness of the targeted hepatitis B vaccination program in Greenland.
AB  - OBJECTIVES: To evaluate the effectiveness of the hepatitis B virus (HBV)
      vaccination program in Greenland, which targets children born to mothers who are
      positive for HBV surface antigen (HBsAg), we determined vaccination coverage,
      levels of postvaccination antibodies, and frequency of breakthrough infections in
      at-risk children. METHODS: We conducted a population-based retrospective cohort
      study with data from nationwide registries. We identified all children born to
      HBsAg-positive mothers from 1992 to 2007 and collected data on their HBV
      vaccination status. In 2008 to 2010, we tested the children for HBV core
      antibody, HBsAg, and anti-HBsAg antibody (HBsAb). RESULTS: Of 4050 pregnant
      women, 3.2% were HBsAg positive. Of 207 children born to these women, 20%
      received no vaccinations, and only 58% received at least 3 vaccinations. At
      follow-up, HBsAb levels in vaccinated children were much lower than expected, and
      8 (6%) of 140 at-risk children had breakthrough infections, with 4 chronically
      infected (persistently HBsAg positive). CONCLUSIONS: The prevention program
      targeting children at risk for HBV in Greenland is ineffective. HBV vaccination
      should be included in the universal childhood vaccination program, and
      postvaccination HBsAb levels should be monitored.

PMID- 21940915
TI  - Future infectious disease threats to Europe.
AB  - We examined how different drivers of infectious disease could interact to
      threaten control efforts in Europe. We considered projected trends through 2020
      for 3 broad groups of drivers: globalization and environmental change, social and
      demographic change, and health system capacity. Eight plausible infectious
      disease threats with the potential to be significantly more problematic than they
      are today were identified through an expert consultation: extensively drug
      resistant bacteria, vector-borne diseases, sexually transmitted infections, food
      borne infections, a resurgence of vaccine-preventable diseases, health care
      associated infections, multidrug-resistant tuberculosis, and pandemic influenza.
      Preemptive measures to be taken by the public health community to counteract
      these threats were identified.

PMID- 21940916
TI  - An agenda for research on the sustainability of public health programs.
AB  - Funders of programs in public health and community health are increasingly
      concerned about the sustainability of changes they initiate. Despite a recent
      increase in sustainability research and evaluation, this literature has not
      developed a widely used paradigm for conducting research that can accumulate into
      generalizable findings. We provide guidance for research and evaluation of health
      program sustainability, including definitions and types of sustainability,
      specifications and measurements of dependent variables, definitions of
      independent variables or factors that influence sustainability, and suggestions
      for designs for research and data collection. We suggest viewing sustainability
      research as a further stage in the translation or dissemination of research-based
      interventions into practice. This perspective emphasizes ongoing relationships
      with earlier stages of a broader diffusion framework, including adoption and
      implementation processes.

PMID- 21940917
TI  - Problems in reporting sexual violence prevalence.

PMID- 21940918
TI  - Weqaya: a population-wide cardiovascular screening program in Abu Dhabi, United
      Arab Emirates.
AB  - OBJECTIVES: We sought to determine cardiovascular risk factor prevalence rates
      among adults in Abu Dhabi, United Arab Emirates. METHODS: We used self-reported
      indicators, anthropometric measures, and blood tests to screen 50 ,138 adults
      aged 18 years or older taking part in a population-wide cardiovascular screening
      program. RESULTS: Participants' mean age was 36.82 years (SD = 14.3); 43% were
      men. Risk factor prevalence rates were as follows: obesity, 35%; overweight, 32%;
      central obesity, 55%; diabetes, 18%; prediabetes, 27%; dyslipidemia, 44%; and
      hypertension, 23.1%. In addition, 26% of men were smokers, compared with 0.8% of
      women. Age-standardized diabetes and prediabetes rates were 25% and 30%,
      respectively, and age-standardized rates of obesity and overweight were 41% and
      34%. CONCLUSIONS: This population-wide cardiovascular screening program
      demonstrated a high cardiovascular burden for our small sample in Abu Dhabi. The
      data form a baseline against which interventions can be implemented and progress
      monitored as part of the population-wide Abu Dhabi Cardiovascular Disease
      Program.

PMID- 21940919
TI  - Rapid increases in overweight and obesity among South African adolescents:
      comparison of data from the South African National Youth Risk Behaviour Survey in
      2002 and 2008.
AB  - OBJECTIVES: To aid future policy and intervention initiatives, we studied the
      prevalence and correlates of overweight and obesity among participants in the
      South African National Youth Risk Behaviour Survey in 2002 and 2008. METHODS: The
      survey collected data from nationally representative cross-sectional samples of
      students in grades 8 through 11 (n = 9491 in 2002 and 9442 in 2008) by
      questionnaire and measurement of height and weight. We stratified data on
      overweight and obesity rates by age, socioeconomic status, and race/ethnicity.
      RESULTS: Among male adolescents, overweight rates increased from 6.3% in 2002 to
      11.0% in 2008 (P < .01); among female adolescents, overweight rates increased
      from 24.3% in 2002 to 29.0% in 2008 (P < .01). Obesity rates more than doubled
      among male adolescents from 1.6% in 2002 to 3.3% in 2008 (P < .01) and rose from
      5.0% to 7.5% among female adolescents (P < .01). We observed a dose-response
      relationship in overweight and obesity rates across socioeconomic categories.
      Rates of overweight and obesity were significantly higher among urban youths than
      among rural youths (P < .01). CONCLUSIONS: South Africa is experiencing a chronic
      disease risk transition. Further research is needed to better understand and
      effectively address this rapid change.

PMID- 21940920
TI  - Social network concordance in food choice among spouses, friends, and siblings.
AB  - OBJECTIVES: We investigated whether eating behaviors were concordant among
      diverse sets of social ties. METHODS: We analyzed the socioeconomic and
      demographic distribution of eating among 3418 members of the Framingham Heart
      Study observed from 1991 to 2001. We used a data-classification procedure to
      simplify choices into 7 nonoverlapping patterns that we matched with information
      on social network ties. We used correlation analysis to examine eating
      associations among 4 types of peers (spouses, friends, brothers, and sisters).
      Longitudinal multiple logistic regression was used to evaluate evidence for peer
      influences on eating. RESULTS: Of all peer types, spouses showed the strongest
      concordances in eating patterns over time after adjustment for social contextual
      factors. Across all peers, the eating pattern most likely to be shared by
      socially connected individuals was "alcohol and snacks." Models estimating one's
      current eating pattern on the basis of a peer's prior eating provided supportive
      evidence of a social influence process. CONCLUSIONS: Certain eating patterns
      appeared to be socially transmissible across different kinds of relationships.
      These findings represent an important step in specifying the relevant social
      environment in the study of health behaviors to include eating.

PMID- 21940921
TI  - Wake me up when there's a crisis: progress on state pandemic influenza ethics
      preparedness.
AB  - We assessed the progress since 2005 of state plans for pandemic influenza and
      found that 7 states had recommended steps to further clarify ethical processes or
      decisions; 6 states had made some progress but almost exclusively in hospital
      preparedness. Having a high-level public health leader, such as a health
      department director, committed to ethics was the key determinant of progress.
      Some state health departments may be destined to gain an appreciation for ethics
      through ethical mishaps.

PMID- 21940922
TI  - Physical education, obesity, and academic achievement: a 2-year longitudinal
      investigation of Australian elementary school children.
AB  - OBJECTIVES: We determined whether physical education (PE) taught by specialists
      contributed to academic development and prevention of obesity in elementary
      school children. METHODS: Our 2-year longitudinal study involved 620 boys and
      girls initially in grade 3 in Australia, all receiving 150 minutes per week of
      PE. One group (specialist-taught PE; n = 312) included 90 minutes per week of PE
      from visiting specialists; the other (common-practice PE; n = 308) received all
      PE from generalist classroom teachers. Measurements included percentage of body
      fat (measured by dual-emission x-ray absorptiometry) and writing, numeracy, and
      reading proficiency (by government tests). RESULTS: Compared with common-practice
      PE, specialist-taught PE was associated with a smaller increase in age-related
      percentage of body fat (P = .02). Specialist-taught PE was also associated with
      greater improvements in numeracy (P < .03) and writing (P = .13) scores. There
      was no evidence of a reading effect. CONCLUSIONS: The attenuated age-related
      increases in percentage of body fat and enhanced numeracy development among
      elementary school children receiving PE from specialists provides support for the
      role of PE in both preventive medicine and academic development.

PMID- 21940923
TI  - Impact of introducing the pneumococcal and rotavirus vaccines into the routine
      immunization program in Niger.
AB  - OBJECTIVES: We investigated whether introducing the rotavirus and pneumococcal
      vaccines, which are greatly needed in West Africa, would overwhelm existing
      supply chains (i.e., the series of steps required to get a vaccine from the
      manufacturers to the target population) in Niger. METHODS: As part of the Bill
      and Melinda Gates Foundation-funded Vaccine Modeling Initiative, we developed a
      computational model to determine the impact of introducing these new vaccines to
      Niger's Expanded Program on Immunization vaccine supply chain. RESULTS:
      Introducing either the rotavirus vaccine or the 7-valent pneumococcal conjugate
      vaccine could overwhelm available storage and transport refrigerator space,
      creating bottlenecks that would prevent the flow of vaccines down to the clinics.
      As a result, the availability of all World Health Organization Expanded Program
      on Immunization vaccines to patients might decrease from an average of 69% to
      28.2% (range = 10%-51%). Addition of refrigerator and transport capacity could
      alleviate this bottleneck. CONCLUSIONS: Our results suggest that the effects on
      the vaccine supply chain should be considered when introducing a new vaccine and
      that computational models can help assess evolving needs and prevent problems
      with vaccine delivery.

PMID- 21940924
TI  - Police training to align law enforcement and HIV prevention: preliminary evidence
      from the field.
AB  - Having identified gaps in implementation of Rhode Island's syringe access law and
      police occupational safety education, public health and police professionals
      developed police training to boost legal knowledge, improve syringe access
      attitudes, and address needlestick injuries. Baseline data (94 officers)
      confirmed anxiety about needlestick injuries, poor legal knowledge, and
      occupational risk overestimation. Before training, respondents believed that
      syringe access promotes drug use (51%), increases likelihood of police
      needlestick injuries (58%), and fails to reduce epidemics (38%). Pretraining to
      posttraining evaluation suggested significant shifts in legal and occupational
      safety knowledge; changes in attitudes toward syringe access were promising.
      Training that combines occupational safety with syringe access content can help
      align law enforcement with public health goals. Additional research is needed to
      assess street-level effect and to inform intervention tailoring.

PMID- 21940925
TI  - Estimating the likely public health impact of partner notification for a clinical
      service: an evidence-based algorithm.
AB  - OBJECTIVES: We present the first evidence-based method for estimating public
      health and cost impacts of partner notification (PN) that takes account of sexual
      partnership type. METHODS: Our algorithm uses routine clinical data, probability
      survey data, and transmission parameters. We propose 2 new epidemiological
      concepts to quantify PN impact: "[the] absolute reduction in onward transmission"
      and its reciprocal, "[the] number needed to treat to interrupt transmission"
      (i.e., the number of partners who need to be treated to interrupt 1 onward
      transmission). We demonstrate these concepts for 273 chlamydia cases diagnosed at
      a UK genitourinary medicine clinic. RESULTS: The number needed to treat to
      interrupt transmission (overall, for casual partners, and for regular partners,
      respectively) was 1.47, 1.11, and 2.50, respectively, for men younger than 25
      years; 1.60, 0.83, and 1.25, respectively, for women younger than 25 years; 2.35,
      1.39, and 2.08, respectively, for men older than 25 years; and 2.14, 0.93, and
      2.08, respectively, for women older than 25 years. CONCLUSIONS: PN that targets
      casual partners, rather than regular or live-in partners, prevents more secondary
      transmissions per partnership; it is also more resource intensive, but the public
      health benefit is greater.

PMID- 21940926
TI  - The nature, scope, and development of the global tobacco control epistemic
      community.
AB  - Over the past 50 years, tobacco control has been transformed from a national to a
      global issue, becoming institutionalized in the World Health Organization (WHO)
      Framework Convention on Tobacco Control, the first international public health
      treaty negotiated under the auspices of the WHO. The global tobacco control
      epistemic community, a worldwide network of professionals with a common
      interpretation of the science in tobacco use and control, has contributed to this
      transformation. We investigated the development, structure, and function of this
      community through interviews and archival documents. Professionals in the
      community are bound by values and consensual knowledge developed after years of
      contentious debates undergirded their activities. Although these professionals
      play multiple roles, they recognize that scientific evidence should inform
      advocacy and policy activities. Public health professionals should continue to
      strengthen the links between science and advocacy for policy while being vigilant
      against industry efforts to undermine the scientific evidence on tobacco use and
      control.

PMID- 21940927
TI  - Reexamining the declining effect of age on mortality differentials associated
      with excess body mass: evidence of cohort distortions in the United States.
AB  - OBJECTIVES: I examined age patterns of mortality differentials associated with
      body mass because the declining age effect observed in previous comparisons of
      cross-sectional age groups is susceptible to cohort and period distortions and
      because previous studies used time since baseline as time at risk, making the
      evaluation of age-specific mortality impossible. METHODS: I conducted a
      parametric survival analysis of data from the 1988-1994 National Health and
      Nutrition Examination Survey for 3 cohorts of American men and women born from
      1901 through 1957 and observed from 1988 through 2006 under an age-period-cohort
      framework. RESULTS: Mortality differentials strengthened across cohorts but did
      not decline with age or change over the study period. Because excess overweight
      and obesity mortality increased from earlier cohorts to more recent ones,
      ignoring cohort differences led to a declining age pattern of excess mortality.
      CONCLUSIONS: Cross-sectional age patterns of mortality differentials appear to be
      distorted by cohort differences. Age should be used as risk time to study age
      variations in associations between risk factors and time to event.

PMID- 21940928
TI  - Studies with staggered starts: multiple baseline designs and group-randomized
      trials.
AB  - OBJECTIVES: Multiple baseline designs (MBDs) have been suggested as alternatives
      to group-randomized trials (GRT). We reviewed structural features of MBDs and
      considered their potential effectiveness in public health research. We also
      reviewed the effect of staggered starts on statistical power. METHODS: We
      reviewed the MBD literature to identify key structural features, recent
      suggestions that MBDs be adopted in public health research, and the literature on
      power in GRTs with staggered starts. We also computed power for MBDs and GRTs.
      RESULTS: The features that have contributed to the success of small MBDs in some
      fields are not likely to translate well to public health research. MBDs can be
      more powerful than GRTs under some conditions, but those conditions involve
      assumptions that require careful evaluation in practice. CONCLUSIONS: MBDs will
      often serve better as a complement of rather than as an alternative to GRTs. GRTs
      may employ staggered starts for logistical or ethical reasons, but this will
      always increase their duration and will often increase their cost.

PMID- 21940929
TI  - Stephen Smith (1823-1922): founder of the American Public Health Association.

PMID- 21940930
TI  - It's about time: team-based editing at the American Journal of Public Health.

PMID- 21940931
TI  - Approaching 4 decades of legislation in the national family planning program: an
      analysis of Title X's history from 1970 to 2008.
AB  - Family planning is an important public health activity. Title X (Pub L No. 91
      572), enacted in 1970, remains the only national family planning program in the
      United States dedicated to providing voluntary and confidential services to all
      individuals. We conducted a thematic analysis of Title X's legislative history.
      Of 293 federal bills included in the legislative history, only 20 (6.8%) were
      enacted into law. Regardless of the proposed challenges, limited changes have
      been adopted. Except for technical amendments, bills involving restrictions
      accounted for the highest percentage of enacted bills, demonstrating efforts to
      undermine reproductive health rights. Title X requires political will and
      bipartisan support if it is to continue to protect individuals' reproductive
      rights.

PMID- 21940932
TI  - Strategies for securing funding for abortion under the Hyde Amendment: a
      multistate study of abortion providers' experiences managing Medicaid.
AB  - OBJECTIVES: We investigated systematic barriers, identified by previous research,
      that prevent women from obtaining Medicaid coverage for an abortion even when it
      should legally be available: when the pregnancy resulted from rape or incest or
      threatens the mother's life. We also aimed to document strategies to improve
      access to federal Medicaid funding in qualifying cases. METHODS: We conducted in
      depth interviews from 2007 to 2009 with representatives of 49 facilities that
      provided abortions in 11 states. Interviews focused on participants' experiences
      and strategies in seeking federal Medicaid funding for abortions. We coded data
      both inductively and deductively and analyzed them thematically. RESULTS: Common
      strategies described by the few participants who secured Medicaid funding for
      abortions in cases of rape, incest, and life endangerment were facility-level
      interventions, such as developing relationships with Medicaid staff, building
      savvy billing departments, and encouraging clients to advocate for themselves, as
      well as broader legal and collaborative strategies. CONCLUSIONS: Multipronged
      state-level interventions that combine advocacy, legal, and on-the-ground
      resources show the most promise of increasing access to federal Medicaid funding
      for abortion care.

PMID- 21940933
TI  - Effect of intensity and type of physical activity on mortality: results from the
      Whitehall II cohort study.
AB  - OBJECTIVES: We examined the association of intensity and type of physical
      activity with mortality. METHODS: We assessed the duration of physical activity
      by intensity level and type in 7456 men and women from the Whitehall II Study by
      questionnaire in 1997-1999 (mean +/-SD age = 55.9 +/- 6.0 years) and 5 years
      later. All-cause mortality was assessed until April 2009. RESULTS: A total of 317
      participants died during the mean follow-up of 9.6 years (SD = 2.7). Reporting at
      least 1 hour per week of moderate activity was associated with a 33% (95%
      confidence interval [CI] = 14%, 45%) lower risk of mortality compared with less
      than 1 hour. For all physical activity types examined, except housework, a
      duration of physical activity greater than 0 (>= 3.5 hours for walking) was
      associated with lower mortality in age-adjusted analyses, but only the
      associations with sports (hazard ratio [HR] = 0.71; 95% CI = 0.56, 0.91) and do
      it-yourself activity (HR = 0.68; 95% CI = 0.53, 0.98) remained in fully adjusted
      analyses. CONCLUSIONS: It is important to consider both intensity and type of
      physical activity when examining associations with mortality.

PMID- 21940934
TI  - Balancing vaccine science and national policy objectives: lessons from the
      National Vaccine Injury Compensation Program Omnibus Autism Proceedings.
AB  - The US Court of Federal Claims, which adjudicates cases for the National Vaccine
      Injury Compensation Program, has been confronted with more than 5000 cases
      submitted on behalf of children with autism spectrum disorders, seeking to link
      the condition to vaccination. Through a test case process, the Omnibus Autism
      Proceedings have in every instance found no association between autism spectrum
      disorders and vaccines. However, vaccine advocates have criticized the courts for
      having an overly permissive evidentiary test for causation and for granting
      credence to insupportable accusations of vaccine harm. In fact, the courts have
      functioned as intended and have allowed for a fair hearing of vaccine concerns
      while maintaining confidence in vaccines and providing protection to vaccine
      manufacturers.

PMID- 21940935
TI  - The prevention of global chronic disease and academia: another key area?

PMID- 21940936
TI  - Changing the constitutional landscape for firearms: the US Supreme Court's recent
      Second Amendment decisions.
AB  - In 2 recent cases-with important implications for public health practitioners,
      courts, and researchers-the US Supreme Court changed the landscape for judging
      the constitutionality of firearm laws under the Constitution's Second Amendment.
      In District of Columbia v Heller (2008), the court determined for the first time
      that the Second Amendment grants individuals a personal right to possess handguns
      in their home. In McDonald v City of Chicago (2010), the court concluded that
      this right affects the powers of state and local governments. The court
      identified broad categories of gun laws-other than handgun bans-that remain
      presumptively valid but did not provide a standard to judge their
      constitutionality. We discuss ways that researchers can assist decision makers.

PMID- 21940938
TI  - Mothers' process of decision making for gastrostomy placement.
AB  - In this article we present the findings of an exploration of mothers' discourses
      on decision making for gastrostomy placement for their child. Exploring in-depth
      interviews of a purposive sample, we analyzed the mothers' discourses of the
      decision-making process to understand how their experiences of the process
      influenced their subsequent constructions of decision making. Mothers negotiated
      decision making by reflecting on their personal experiences of feeding their
      child, either orally or via a tube, and interwove their background experiences
      with the communications from members of the health care team until a decision was
      reached. Decision making was often fraught with difficulty, resulting in anxiety
      and guilt. Experiences of decision making ranged from perceived coercion to true
      choice, which encompasses a truly child-centered decision. The resulting impact
      of the decision-making process on the mothers was profound. We conclude with an
      exploration of the implications for clinical practice and describe how health
      care professionals can support mothers to ensure that decision-making processes
      for gastrostomy placement in children are significantly improved.

PMID- 21940937
TI  - Backsliding on a key health investment in Latin America and the Caribbean: the
      case of breastfeeding promotion.
AB  - OBJECTIVES: We examined trends in breastfeeding promotion investments,
      breastfeeding promotion activities, and breastfeeding duration in Latin America
      and the Caribbean from the 1980s to the 2000s. METHODS: We obtained financial
      data from the United States Agency for International Development and the
      International Code Documentation Center, and we obtained breastfeeding promotion
      data from surveys of breastfeeding coordinators with ministries of health and
      with the International Baby Food Action Network. We obtained breastfeeding data
      from nationally representative surveys conducted between 1986 and 2008. RESULTS:
      Investment in breastfeeding promotion declined in the 2000s relative to earlier
      years. For all countries, breastfeeding duration increased between the first and
      last survey. Of the 12 countries represented in the interval when investment in
      breastfeeding promotion was high, breastfeeding duration decreased in 1 country.
      Of the 12 countries represented in the interval when investment was low,
      breastfeeding duration decreased in 3 countries. Nonetheless, the average annual
      change in breastfeeding duration for the 2 intervals was positive and similar
      (0.16 months and 0.21 months). CONCLUSIONS: Breastfeeding promotion likely
      resulted in large improvements in breastfeeding. Investments in breastfeeding
      promotion have declined, but this does not appear to have adversely affected
      breastfeeding duration.

PMID- 21940939
TI  - Canadian care providers' and pregnant women's approaches to managing birth:
      minimizing risk while maximizing integrity.
AB  - We employed grounded theory to explain how Canadian pregnant women and care
      providers manage birth. The sample comprised 9 pregnant women and 56 intrapartum
      care providers (family doctors, midwives, nurses, obstetricians, and doulas
      [individuals providing labor support]). We collected data from 2008 to 2009,
      using focus groups that included care providers and pregnant women. Using
      concurrent data collection and analysis, we generated the core category:
      minimizing risk while maximizing integrity. Women and providers used strategies
      to minimize risk and maximize integrity, which included accepting or resisting
      recommendations for surveillance and recommendations for interventions, and
      plotting courses vs. letting events unfold. Strategies were influenced by
      evidence, relationships, and local health cultures, and led to feelings of
      weakness or strength, confidence or uncertainty, and differing power- and
      responsibility-sharing arrangements. The findings highlight difficulties
      resisting surveillance and interventions in a risk-adverse culture, and the need
      for attention to processes of giving birth.

PMID- 21940941
TI  - Proteomic analysis of polymorphonuclear neutrophils identifies catalase as a
      novel biomarker of abdominal aortic aneurysm: potential implication of oxidative
      stress in abdominal aortic aneurysm progression.
AB  - OBJECTIVE: Polymorphonuclear neutrophils (PMNs) play a main role in abdominal
      aortic aneurysm (AAA) progression. We have analyzed circulating PMNs isolated
      from AAA patients and controls by a proteomic approach to identify proteins
      potentially involved in AAA pathogenesis. METHODS AND RESULTS: PMNs from 8 AAA
      patients (4 large AAA >5 cm and 4 small AAA 3-5 cm) and 4 controls were analyzed
      by 2D differential in-gel electrophoresis. Among differentially expressed spots,
      several proteins involved in redox balance were identified by mass spectrometry
      (eg, cyclophilin, thioredoxin reductase, catalase). Diminished catalase
      expression and activity were observed in PMNs from AAA patients compared with
      controls. In contrast, PMNs from AAA patients displayed higher H(2)O(2) and
      myeloperoxidase levels than PMNs from controls. Moreover, a significant decrease
      in catalase mRNA levels was observed in PMNs after phorbol 12-myristate 13
      acetate incubation. Catalase plasma levels were also decreased in large (n=47)
      and small (n=56) AAA patients compared with controls (n=34). We observed catalase
      expression in AAA thrombus and thrombus-conditioned medium, associated with PMN
      infiltration. Furthermore, increased H(2)O(2) levels were observed in AAA
      thrombus-conditioned medium compared with the media layer. CONCLUSIONS:
      Diminished catalase levels in circulating PMNs and plasma are observed in AAA
      patients, supporting an important role of oxidative stress in AAA evolution.

PMID- 21940940
TI  - Coupling of Fcgamma receptor I to Fcgamma receptor IIb by SRC kinase mediates C
      reactive protein impairment of endothelial function.
AB  - RATIONALE: Elevations in C-reactive protein (CRP) are associated with increased
      cardiovascular disease risk and endothelial dysfunction. CRP antagonizes
      endothelial nitric oxide synthase (eNOS) through processes mediated by the IgG
      receptor Fcgamma receptor IIB (FcgammaRIIB), its immunoreceptor tyrosine-based
      inhibitory motif, and SH2 domain-containing inositol 5'-phosphatase 1. In mice,
      CRP actions on eNOS blunt carotid artery re-endothelialization. OBJECTIVE: How
      CRP activates FcgammaRIIB in endothelium is not known. We determined the role of
      Fcgamma receptor I (FcgammaRI) and the basis for coupling of FcgammaRI to
      FcgammaRIIB in endothelium. METHODS AND RESULTS: In cultured endothelial cells,
      FcgammaRI-blocking antibodies prevented CRP antagonism of eNOS, and CRP activated
      Src via FcgammaRI. CRP-induced increases in FcgammaRIIB immunoreceptor tyrosine
      based inhibitory motif phosphorylation and SH2 domain-containing inositol 5'
      phosphatase 1 activation were Src-dependent, and Src inhibition prevented eNOS
      antagonism by CRP. Similar processes mediated eNOS antagonism by aggregated IgG
      used to mimic immune complex. Carotid artery re-endothelialization was evaluated
      in offspring from crosses of CRP transgenic mice (TG-CRP) with either mice
      lacking the gamma subunit of FcgammaRI (FcRgamma(-/-)) or FcgammaRIIB(-/-) mice.
      Whereas re-endothelialization was impaired in TG-CRP vs wild-type, it was normal
      in both FcRgamma(-/-); TG-CRP and FcgammaRIIB(-/-); TG-CRP mice. CONCLUSIONS: CRP
      antagonism of eNOS is mediated by the coupling of FcgammaRI to FcgammaRIIB by Src
      kinase and resulting activation of SH2 domain-containing inositol 5'-phosphatase
      1, and consistent with this mechanism, both FcgammaRI and FcgammaRIIB are
      required for CRP to blunt endothelial repair in vivo. Similar mechanisms underlie
      eNOS antagonism by immune complex. FcgammaRI and FcgammaRIIB may be novel
      therapeutic targets for preventing endothelial dysfunction in inflammatory or
      immune complex-mediated conditions.

PMID- 21940942
TI  - Homozygosity for an allele encoding deacetylated FoxO1 protects macrophages from
      cholesterol-induced inflammation without increasing apoptosis.
AB  - OBJECTIVE: Insulin resistance renders macrophages more prone to cholesterol
      induced apoptosis by promoting nuclear localization of transcription factor
      forkhead box transcription factor (Fox) O1. However, FoxO1 also decreases
      macrophage inflammation, raising the question of how the balance between
      proapoptotic and antiinflammatory effects is determined. We sought to identify
      the mechanism whereby FoxO1 dampens inflammation without promoting apoptosis. We
      hypothesized that nutrient-dependent FoxO1 acetylation plays a role in this
      process. METHODS AND RESULTS: We generated knock-in mice bearing alleles that
      encode constitutively deacetylated FoxO1 and studied the ex vivo response of
      primary peritoneal macrophages. We show that macrophages derived from mice
      homozygous for constitutively deacetylated FoxO1 alleles retain antiinflammatory
      properties in response to free cholesterol loading, without increasing apoptosis.
      Deacetylated FoxO1 inhibits free cholesterol-induced Akt phosphorylation and
      increases levels of the nuclear factor-kappaB precursor p105, decreasing nuclear
      translocation of nuclear factor-kappaB p65 subunit and dampening mitogen
      activated protein/extracellular signal-regulated kinase activation to prevent
      inflammation. CONCLUSIONS: Deacetylated FoxO1 regulates p105 to prevent
      macrophage inflammation without causing apoptosis, suggesting a potential novel
      therapeutic approach to atherosclerosis through FoxO1 deacetylation.

PMID- 21940943
TI  - Integrin-targeted imaging of inflammation in vascular remodeling.
AB  - OBJECTIVE: Inflammation plays a key role in the development of vascular diseases.
      Monocytes and macrophages express alpha(v)beta(3) integrin. We used an alpha(v)
      integrin-specific tracer, (99m)Tc-NC100692, to investigate integrin-targeted
      imaging for detection vessel wall inflammation. METHODS AND RESULTS: The binding
      of a fluorescent homologue of NC100692 to alpha(v)beta(3) on human monocytes and
      macrophages was shown by flow cytometry. Vessel wall inflammation and remodeling
      was induced in murine carotid arteries through adventitial exposure to CaCl(2).
      NC100692 micro single photon computed tomography/CT imaging was performed after 2
      and 4 weeks and showed significantly higher uptake of the tracer in CaCl(2)
      exposed left carotids compared with sham-operated contralateral arteries.
      Histological analysis at 4 weeks demonstrated significant remodeling of left
      carotid arteries and considerable macrophage infiltration, which was confirmed by
      real-time polymerase chain reaction. There was no significant difference in
      normalized alpha(v), beta(3), or beta(5) mRNA expression between right and left
      carotid arteries. Finally, NC100692 uptake strongly correlated with macrophage
      marker expression in carotid arteries. CONCLUSIONS: NC100692 imaging can detect
      vessel wall inflammation in vivo. If further validated, alpha(v)-targeted imaging
      may provide a noninvasive approach for identifying patients who are at high risk
      for vascular events and tracking the effect of antiinflammatory treatments.

PMID- 21940944
TI  - Pericyte-derived sphingosine 1-phosphate induces the expression of adhesion
      proteins and modulates the retinal endothelial cell barrier.
AB  - OBJECTIVE: The mechanisms that regulate the physical interaction of pericytes and
      endothelial cells and the effects of these interactions on interendothelial cell
      junctions are not well understood. We determined the extent to which vascular
      pericytes could regulate pericyte-endothelial adhesion and the consequences that
      this disruption might have on the function of the endothelial barrier. METHODS
      AND RESULTS: Human retinal microvascular endothelial cells were cocultured with
      pericytes, and the effect on the monolayer resistance of endothelial cells and
      expression of the cell junction molecules N-cadherin and VE-cadherin were
      measured. The molecules responsible for the effect of pericytes or pericyte
      conditioned media on the endothelial resistance and cell junction molecules were
      further analyzed. Our results indicate that pericytes increase the barrier
      properties of endothelial cell monolayers. This barrier function is maintained
      through the secretion of pericyte-derived sphingosine 1-phosphate. Sphingosine 1
      phosphate aids in maintenance of microvascular stability by upregulating the
      expression of N-cadherin and VE-cadherin, and downregulating the expression of
      angiopoietin 2. CONCLUSIONS: Under normal circumstances, the retinal vascular
      pericytes maintain pericyte-endothelial contacts and vascular barrier function
      through the secretion of sphingosine 1-phosphate. Alteration of pericyte-derived
      sphingosine 1-phosphate production may be an important mechanism in the
      development of diseases characterized by vascular dysfunction and increased
      permeability.

PMID- 21940945
TI  - Novel in vivo method for measuring cholesterol mass flux in peripheral
      macrophages.
AB  - OBJECTIVE: Reverse cholesterol transport is the process by which excess
      cholesterol is removed from peripheral tissue by HDL and delivered to the liver
      for excretion. Presently, methods of measuring in vivo reverse cholesterol
      transport do so by monitoring the appearance in the feces of labeled cholesterol
      that originated from peripheral macrophage foam cells. These methods do not
      account for changes in macrophage cholesterol mass. We have developed an in vivo
      assay to measure cholesterol mass changes in atherosclerotic foam cells. METHODS
      AND RESULTS: Macrophages are entrapped in semipermeable (pore size 0.2 MUm)
      hollow fibers and surgically implanted into the peritoneum of recipient mice. The
      fibers are removed from the peritoneum 24 hours after implantation. This method
      allows the complete recovery of the macrophages for quantification of changes in
      cholesterol mass and cellular protein. In wild-type mice we measured a
      significant reduction in total cell cholesterol (TC) when hollow fibers
      containing cholesterol-enriched macrophage cells were implanted (TC before
      implantation=105+/-18 MUg/mg cell protein, TC 24 hours after implantation=60+/-16
      MUg/mg protein). Additionally, there was an increase in cholesterol content when
      hollow fibers containing cholesterol-normal macrophages were implanted in an
      atherogenic mouse model (LDLr/apobec dko) compared to a wild-type mouse (initial
      TC content=57+/-24 MUg/mg protein, TC 24 hours after implantation: wild-type
      mice=52+/-10 MUg/mg protein; LDLr/apobec dko mice=118+/-27 MUg/mg protein).
      CONCLUSIONS: This assay can quantify in vivo both cholesterol mass accumulation,
      and reduction, in macrophages. This method permits quantitative analysis of the
      progression and regression of foam cells.

PMID- 21940946
TI  - AMP-activated protein kinase suppresses endothelial cell inflammation through
      phosphorylation of transcriptional coactivator p300.
AB  - OBJECTIVE: Considerable evidence supports the early involvement of
      monocyte/macrophage recruitment to activated endothelial cells by leukocyte
      adhesion molecules during atherogenesis. AMP-activated protein kinase (AMPK) is
      highly expressed in vascular endothelial cells, but its impact on monocyte
      adhesion and the related mechanisms are not fully understood. The present study
      was designed to evaluate the impact of and gain mechanistic insight into the
      signaling coupling AMPK function to the antiinflammatory response. METHODS AND
      RESULTS: 5-Aminoimidazole-4-carboxamide-1-beta-D-ribonucleotide (AICAR) treatment
      or overexpression of constitutively active AMPK markedly reduced human monocytic
      human acute monocytic leukemia cell line-1 cell adhesion and the expression of
      vascular cell adhesion molecule-1 in tumor necrosis factor-alpha-activated human
      aortic endothelial cells. Furthermore, AICAR or constitutively active AMPK
      overexpression strongly inhibited the histone acetyltransferase activity of the
      transcriptional coactivator p300 by phosphorylation of Ser89, which in turn
      decreased tumor necrosis factor-alpha-activated p300-mediated acetylation of
      nuclear factor-kappaB p65 on Lys221 and reduced the DNA binding activity of
      nuclear factor-kappaB by inhibiting its recruitment to its target gene promoters.
      AMPK phosphorylates the transcriptional coactivator p300 via the atypical protein
      kinase Ciota/lambda. CONCLUSIONS: Our findings demonstrate that transcriptional
      coactivator p300 phosphorylation at Ser89 by AMPK is critical for the therapeutic
      effect of AMPK and may be a potential target for pharmaceutical intervention in
      inflammatory diseases such as atherosclerosis.

PMID- 21940947
TI  - Passive exercise using whole-body periodic acceleration enhances blood supply to
      ischemic hindlimb.
AB  - OBJECTIVE: Whole-body periodic acceleration (WBPA) has been developed as a
      passive exercise technique to improve endothelial function by increasing shear
      stress through repetitive movements in spinal axis direction. We investigated the
      effects of WBPA on blood flow recovery in a mouse model of hindlimb ischemia and
      in patients with peripheral arterial disease. METHODS AND RESULTS: After
      unilateral femoral artery excision, mice were assigned to either the WBPA (n=15)
      or the control (n=13) group. WBPA was applied at 150 cpm for 45 minutes under
      anesthesia once a day. WBPA significantly increased blood flow recovery after
      ischemic surgery, as determined by laser Doppler perfusion imaging. Sections of
      ischemic adductor muscle stained with anti-CD31 antibody showed a significant
      increase in capillary density in WBPA mice compared with control mice. WBPA
      increased the phosphorylation of endothelial nitric oxide synthase (eNOS) in
      skeletal muscle. The proangiogenic effect of WBPA on ischemic limb was blunted in
      eNOS-deficient mice, suggesting that the stimulatory effects of WBPA on
      revascularization are eNOS dependent. Quantitative real-time polymerase chain
      reaction analysis showed significant increases in angiogenic growth factor
      expression in ischemic hindlimb by WBPA. Facilitated blood flow recovery was
      observed in a mouse model of diabetes despite there being no changes in glucose
      tolerance and insulin sensitivity. Furthermore, both a single session and 7-day
      repeated sessions of WBPA significantly improved blood flow in the lower
      extremity of patients with peripheral arterial disease. CONCLUSIONS: WBPA
      increased blood supply to ischemic lower extremities through activation of eNOS
      signaling and upregulation of proangiogenic growth factor in ischemic skeletal
      muscle. WBPA is a potentially suitable noninvasive intervention to facilitate
      therapeutic angiogenesis.

PMID- 21940948
TI  - Positive cross-talk between hypoxia inducible factor-1alpha and liver X receptor
      alpha induces formation of triglyceride-loaded foam cells.
AB  - OBJECTIVE: Atherosclerosis is a chronic and progressive inflammatory disease of
      the arteries that is characterized by subendothelial accumulation of lipid-rich
      macrophages, called foam cells. We sought to identify the molecular details of
      cross-talk between liver X receptor alpha (LXRalpha) and hypoxia-inducible factor
      1alpha (HIF-1alpha) for the formation of triglyceride-rich foam cells under
      hypoxic conditions. METHODS AND RESULTS: We first observed that expression of
      LXRalpha and its target lipogenic genes was time-dependently induced in human
      primary macrophages and RAW 264.7 cells under hypoxia. Similarly, TO901317, an
      activator of LXRalpha, enhanced the expression level and the transcriptional
      activity of HIF-1alpha. Second, we demonstrated that LXRalpha increased HIF
      1alpha protein stability through a physical interaction between the ligand
      binding domain of LXRalpha and the oxygen-dependent degradation domain of HIF
      1alpha. Third, we found that the activation of HIF-1alpha or LXRalpha
      synergistically induced triglyceride accumulation in macrophages. Finally, we
      showed that LXRalpha and HIF-1alpha were codistributed in the macrophages of
      atherosclerotic lesions of patients. CONCLUSIONS: These results suggest that the
      positive feed-forward regulation of transcriptional activity and protein
      stability of LXRalpha and HIF-1alpha has an important impact in foam cell
      formation.

PMID- 21940949
TI  - Serum response factor regulates expression of phosphatase and tensin homolog
      through a microRNA network in vascular smooth muscle cells.
AB  - OBJECTIVE: Serum response factor (SRF) is a critical transcription factor in
      smooth muscle cells (SMCs) controlling differentiation and proliferation. Our
      previous work demonstrated that depleting SRF in cultured SMCs decreased
      expression of SMC markers but increased proliferation and inflammatory mediators.
      A similar phenotype has been observed in SMCs silenced for phosphatase and tensin
      homolog (PTEN), suggesting that SRF and PTEN may lie on a common pathway. Our
      goal was to determine the effect of SRF depletion on PTEN levels and define
      mechanisms mediating this effect. METHODS AND RESULTS: In SRF-silenced SMCs, PTEN
      protein levels but not mRNA levels were decreased, suggesting posttranscriptional
      regulation. Reintroduction of PTEN into SRF-depleted SMCs reversed increases in
      proliferation and cytokine/chemokine production but had no effect on SMC marker
      expression. SRF-depleted cells showed decreased levels of microRNA (miR)-143 and
      increased miR-21, which was sufficient to suppress PTEN. Increased miR-21
      expression was dependent on induction of Fos related antigen (FRA)-1, which is a
      direct target of miR-143. Introducing miR-143 into SRF-depleted SMCs reduced FRA
      1 expression and miR-21 levels and restored PTEN expression. CONCLUSIONS: SRF
      regulates PTEN expression in SMCs through a miR network involving miR-143,
      targeting FRA-1, which regulates miR-21. Cross-talk between SRF and PTEN likely
      represents a critical axis in phenotypic remodeling of SMCs.

PMID- 21940950
TI  - Fetal growth and preterm birth influence cardiovascular risk factors and arterial
      health in young adults: the Cardiovascular Risk in Young Finns Study.
AB  - OBJECTIVE: Impaired fetal growth is associated with cardiovascular disease in
      adulthood. The mechanisms of this association remain poorly described. We aimed
      to determine the associations of impaired fetal growth and preterm birth with
      cardiovascular risk factors and arterial health in a large cohort of young
      adults. METHODS AND RESULTS: Carotid intima-media thickness, brachial flow
      mediated dilatation and cardiovascular risk factors were compared between young
      adults (24-45 years) born at term with impaired fetal growth (birth weight <10th
      percentile; n=207), born preterm (<37 weeks' gestation; n=253), and a control
      group born at term with normal fetal growth (birth weight 50-90th percentile;
      n=835), in the Cardiovascular Risk in Young Finns study. Compared with controls,
      those with impaired fetal growth had elevated triglycerides (P=0.006), C-reactive
      protein (P=0.004), low-density lipoprotein cholesterol, systolic blood pressure
      (both P=0.06), and intima-media thickness and impaired flow-mediated dilatation
      (both P=0.02), the latter partially mediated by systolic blood pressure, C
      reactive protein, and triglycerides. Those born preterm had higher intima-media
      thickness (P=0.005) and lower flow-mediated dilatation (P=0.03) compared with
      controls, although this was restricted to those with concurrent fetal growth
      restriction. CONCLUSIONS: Impaired fetal growth is associated with impaired
      endothelial function and elevated preclinical atherosclerosis in young adults,
      partly mediated by inflammation, blood pressure, and triglycerides. This
      association is most marked for those also born preterm.

PMID- 21940951
TI  - Notch3 Arg170Cys knock-in mice display pathologic and clinical features of the
      neurovascular disorder cerebral autosomal dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy.
AB  - OBJECTIVE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) is an adult-onset neurovascular disorder caused by
      stereotyped mutations in the NOTCH3 receptor. Elucidation of its pathobiology is
      still incomplete and remains a challenge, in part because the available
      preclinical mouse models to date do not reproduce the full spectrum of CADASIL
      pathology and clinical disease. METHODS AND RESULTS: Here, we report a novel
      knock-in mouse with Arg170Cys substitution in murine Notch3, corresponding to the
      prevalent Arg169Cys substitution in CADASIL. The Notch3(Arg170Cys) mice displayed
      late-onset, dominant CADASIL arteriopathy with typical granular osmiophilic
      material deposition and developed brain histopathology including thrombosis,
      microbleeds, gliosis, and microinfarction. Furthermore, Notch3(Arg170Cys) mice
      experienced neurological symptoms with motor defects such as staggering gait and
      limb paresis. CONCLUSIONS: This model, for the first time, phenocopies the
      arteriopathy and the histopathologic as well as clinical features of CADASIL and
      may offer novel opportunities to investigate disease pathogenesis.

PMID- 21940952
TI  - Protease-activated receptor-2 modulates protease-activated receptor-1-driven
      neointimal hyperplasia.
AB  - OBJECTIVE: Emerging evidence suggests that protease-activated receptors-1 and -2
      (PAR1 and PAR2) can signal together in response to proteases found in the rapidly
      changing microenvironment of damaged blood vessels. However, it is unknown
      whether PAR1 and PAR2 promote or mitigate the hyperplastic response to arterial
      injury. Using cell-penetrating PAR1 pepducins and mice deficient in PAR1 or PAR2,
      we set out to determine the respective contributions of the receptors to
      hyperplasia and phenotypic modulation of smooth muscle cells (SMCs) in response
      to arterial injury. METHODS AND RESULTS: SMCs were strongly activated by PAR1
      stimulation, as evidenced by increased mitogenesis, mitochondrial activity, and
      calcium mobilization. The effects of chronic PAR1 stimulation following vascular
      injury were studied by performing carotid artery ligations in mice treated with
      the PAR1 agonist pepducin, P1pal-13. Histological analysis revealed that PAR1
      stimulation caused striking hyperplasia, which was ablated in PAR1(-/-) and,
      surprisingly, PAR2(-/-) mice. P1pal-13 treatment yielded an expression pattern
      consistent with a dedifferentiated phenotype in carotid artery SMCs. Detection of
      PAR1-PAR2 complexes provided an explanation for the hyperplastic effects of the
      PAR1 agonist requiring the presence of both receptors. CONCLUSIONS: We conclude
      that PAR2 regulates the PAR1 hyperplastic response to arterial injury leading to
      stenosis.

PMID- 21940953
TI  - Lipoprotein (a) and carotid atherosclerosis in young patients with stroke.
AB  - BACKGROUND AND PURPOSE: Elevated lipoprotein (a) concentration is associated with
      carotid atherosclerosis in middle-aged and older patients with ischemic stroke.
      This association has not been explored in young patients with stroke. METHODS: A
      retrospective analysis of data from patients aged 16 to 54 years consecutively
      treated for acute ischemic stroke in a tertiary stroke unit during 4.5 years was
      performed. We graded carotid atherosclerosis using carotid duplex as: no
      atherosclerosis (A); plaque without stenosis (B); or stenosis>=50% (C). RESULTS:
      One hundred ninety-six patients were included (male/female: 119/77; mean age+/
      SD: 44.3+/-8.6 years): 115 in Group A; 67 in Group B; and 14 in Group C.
      Multivariate analysis using polynomial logistic regression showed a graded
      association of lipoprotein (a) plasma concentration with carotid atherosclerosis
      (P<0.001). CONCLUSIONS: Our results showed a positive association of lipoprotein
      (a) plasma concentration with carotid atherosclerosis in young adults with
      ischemic stroke. This association was strong, graded, and independent of
      traditional risk factors including cholesterol.

PMID- 21940955
TI  - Letter by Blackburn et al regarding article, "Is the Montreal cognitive
      assessment superior to the mini-mental state examination to detect poststroke
      cognitive impairment? A study with neuropsychological evaluation".

PMID- 21940954
TI  - Carotid intima-media thickness, electrocardiographic left ventricular
      hypertrophy, and incidence of intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: Carotid intima-media thickness and electrocardiographic
      left ventricular hypertrophy are 2 subclinical cardiovascular disease measures
      associated with increased risk of total and ischemic strokes. Increased intima
      media thickness and electrocardiographic left ventricular hypertrophy also may
      reflect end-organ hypertensive effects. Information is scant on the associations
      of these subclinical measures with intracerebral hemorrhage (ICH). We
      hypothesized that greater carotid intima-media thickness and the presence of
      electrocardiographic left ventricular hypertrophy would be independently
      associated with increased ICH incidence. METHODS: Among 18,155 participants
      initially free of stroke in the Atherosclerosis Risk in Communities Study (ARIC)
      and the Cardiovascular Health Study (CHS), we assessed carotid intima-media
      thickness, carotid plaque, and electrocardiographic left ventricular hypertrophy.
      Over a median of 18 years of follow-up, 162 incident ICH events occurred.
      RESULTS: After adjustment for other ICH risk factors, carotid intima-media
      thickness was associated positively with incidence of ICH in both ARIC and CHS.
      The risk was lowest in study-specific Quartile 1, elevated 1.6- to 2.6-fold in
      Quartiles 2 to 3, and elevated 2.5 to 3.7-fold in Quartile 4 (P<0.05 for both
      studies). In CHS, having a carotid plaque was associated with a 2-fold (95% CI,
      1.1-3.4) greater ICH risk than having no plaque, but only 1.2-fold (95% CI, 0.76
      2.0) greater ICH risk in ARIC. Electrocardiographic left ventricular hypertrophy
      carried a hazard ratio of ICH of 1.7 (95% CI, 0.77-3.7) in CHS and 2.8 (95% CI,
      1.2-6.4) in ARIC. CONCLUSIONS: Our data suggest that people with carotid
      atherosclerosis and possibly left ventricular hypertrophy are at increased risk
      not only of ischemic stroke, but also of ICH.

PMID- 21940956
TI  - Physical activity and functional outcomes from cerebral vascular events in men.
AB  - BACKGROUND AND PURPOSE: In studies enrolling patients with stroke, higher levels
      of prestroke physical activity are associated with better functional outcomes.
      However, prospective studies evaluating this association are sparse. Using a
      cohort of initially healthy men, we aimed to prospectively assess the association
      between physical activity and functional outcomes from cerebral vascular events.
      METHODS: We conducted a prospective cohort study among 21 794 men enrolled in the
      Physician's Health Study who provided information on physical activity at
      baseline and who did not have a history of stroke or transient ischemic attack
      (TIA). Baseline levels of physical activity were categorized as: vigorous
      exercise<1, 1, 2 to 4, and >=5 times/week. Possible functional outcomes included
      TIA and stroke with modified Rankin Scale score of 0 to 1, 2 to 3, or 5 to 6.
      Multinomial logistic regression was used to determine the association between
      physical activity and functional outcomes from cerebral vascular events. RESULTS:
      After a mean of 20.2 years of follow-up, 761 TIAs, 1146 ischemic strokes, 221
      hemorrhagic strokes, and 11 strokes of unknown type occurred. Compared with men
      who did not experience a stroke or TIA and who exercise vigorously<1 time/week,
      men who exercise vigorously>=5 times/week had adjusted relative risk (95% CIs) of
      0.67 (0.53-0.86) for TIA, 0.84 (0.61-1.14) for stroke with modified Rankin Scale
      score 0 to 1, 0.85 (0.67-1.08) for modified Rankin Scale score 2 to 3, and 1.12
      (0.78-1.60) for modified Rankin Scale score 5 to 6 after total stroke. Other
      levels of physical activity did not have a significant impact on the risk of our
      outcomes. CONCLUSIONS: Physical activity before TIA or stroke does not appear to
      influence functional outcomes after cerebral vascular events.

PMID- 21940957
TI  - Atherosclerosis and dementia: a cross-sectional study with pathological analysis
      of the carotid arteries.
AB  - BACKGROUND AND PURPOSE: Previous ultrasound-based studies have shown an
      association between carotid artery atherosclerosis and dementia. Our aim was to
      investigate this association using postmortem examination. METHODS: Postmortem
      morphometric measurements of carotid stenosis and intima-media thickness were
      performed in individuals with dementia (n=112) and control subjects (n=577).
      Multivariate logistic regression models were applied. RESULTS: High-grade left
      internal carotid stenosis (>=70%) was associated with increased odds for dementia
      (OR, 2.30; 95% CI, 1.14-4.74; P=0.02). Intima-media thickness was not associated
      with dementia. CONCLUSIONS: The likelihood of dementia is increased with high
      grade left internal carotid artery atherosclerosis after adjusting for
      demographic and cardiovascular risk factors.

PMID- 21940958
TI  - Neuroprotection by interleukin-6 is mediated by signal transducer and activator
      of transcription 3 and antioxidative signaling in ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Interleukin-6 (IL-6) has been shown to have a
      neuroprotective effect in brain ischemic injury. However, its molecular
      mechanisms are still poorly understood. In this study, we investigated the
      neuroprotective role of the IL-6 receptor (IL-6R) by IL-6 in the reactive oxygen
      species defense system after transient focal cerebral ischemia (tFCI). METHODS:
      IL-6 was injected in mice before and after middle cerebral artery occlusion.
      Coimmunoprecipitation assays were performed for analysis of an IL-6R association
      after tFCI. Primary mouse cerebral cortical neurons were transfected with small
      interfering RNA probes targeted to IL-6Ralpha or gp130 and were used for
      chromatin-immunoprecipitation assay, luciferase promoter assay, and cell
      viability assay. Reduction in infarct volumes by IL-6 was measured after tFCI.
      RESULTS: IL-6R was disrupted through a disassembly between IL-6Ralpha and gp130
      associated by protein oxidation after reperfusion after tFCI. This suppressed
      phosphorylation of signal transducer and activator of transcription 3 (STAT3) and
      finally induced neuronal cell death through a decrease in manganese-superoxide
      dismutase. However, IL-6 injections prevented disruption of IL-6R against
      reperfusion after tFCI, consequently restoring activity of STAT3 through recovery
      of the binding of STAT3 to gp130. Moreover, IL-6 injections restored the
      transcriptional activity of the manganese-superoxide dismutase promoter through
      recovery of the recruitment of STAT3 to the manganese-superoxide dismutase
      promoter and reduced infarct volume after tFCI. CONCLUSIONS: This study
      demonstrates that IL-6 has a neuroprotective effect against cerebral ischemic
      injury through IL-6R-mediated STAT3 activation and manganese-superoxide dismutase
      expression.

PMID- 21940959
TI  - The deleterious effect of admission hyperglycemia on survival and functional
      outcome in patients with intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: We aimed to evaluate the association between blood
      glucose (BG) levels at admission and both functional outcome at discharge and 1
      month mortality after intracerebral hemorrhage (ICH). METHODS: All cases of first
      ever ICH were identified from the population-based Stroke Registry of Dijon,
      France from 1985 to 2009. Clinical and radiological information was recorded. BG
      was measured at admission. Multivariate analyses were performed using logistic
      and Cox regression models. Multiple imputation was used as a sensitivity
      analysis. RESULTS: We recorded 465 first-ever ICH. BG at admission was obtained
      in 416 patients (89.5%) with a median value of 6.92 mmol/L. In multivariate
      analyses, BG in the highest tertile (>=8.6 mmol/L) was an independent predictor
      of functional handicap (odds ratio, 2.51; 95% CI, 1.43-4.40; P=0.01) and 1-month
      mortality (hazard ratio, 2.51; 95% CI, 1.23-2.43; P=0.002). The results were
      consistent with those obtained from multiple imputation analyses. CONCLUSIONS:
      Admission hyperglycemia is associated with poor functional recovery at discharge
      and 1-month mortality after ICH. These results suggest a need for trials that
      evaluate strategies to lower BG in acute ICH.

PMID- 21940960
TI  - Telomerase reverse transcriptase upregulation attenuates astrocyte proliferation
      and promotes neuronal survival in the hypoxic-ischemic rat brain.
AB  - BACKGROUND AND PURPOSE: Telomerase reverse transcriptase (TERT) is tightly
      related to the resistance of cells to stress and injury. However, little is known
      about the roles of TERT in the nervous system. We try to investigate the effects
      of TERT on the function of astrocytes in developing rat brains subjected to
      hypoxia-ischemia. METHODS: TERT expression was detected in rat brains with
      hypoxia-ischemia. In in vitro study, the function of astrocytes with TERT
      overexpression was measured, and the effects of astrocyte on neuronal apoptosis
      were examined. Moreover, overexpression or inhibition of TERT was conducted in
      vivo by gene transduction. Astrocyte proliferation was examined through Ki67
      staining. Terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling
      staining and brain infarct volume calculation were used to detect neuronal
      injury. RESULTS: Both TERT mRNA and protein were upregulated in neurons within 2
      days but shifted to astrocytes at Day 3 after hypoxia-ischemia. Astrocyte
      proliferation was inhibited with TERT overexpression due to the upregulation of
      cell-cycle regulatory protein p15. Meanwhile, the apoptosis of neurons increased,
      whereas neurons were cocultured with conditioned media from astrocytes with TERT
      inhibition compared with TERT overexpression due to the decrease of neurotrophin
      3 expression in astrocytes. Furthermore, Ki67-positive astrocytes and neuronal
      injury were found to be inhibited in TERT-overexpressing rat brains with hypoxia
      ischemia. CONCLUSIONS: TERT attenuates astrocyte proliferation and promotes
      neuronal survival in the developing rat brain after hypoxia-ischemia, partly
      through its enhancement of p15 and neurotrophin-3 expression in astrocytes.

PMID- 21940961
TI  - Comprehensive cardiac rehabilitation for secondary prevention after transient
      ischemic attack or mild stroke: I: feasibility and risk factors.
AB  - BACKGROUND AND PURPOSE: Comprehensive cardiac rehabilitation (CCR), which
      integrates structured lifestyle interventions and medications, reduces morbidity
      and mortality among cardiac patients. CCR has not typically been used with
      cerebrovascular populations, despite important commonalities with heart patients.
      We tested feasibility and effectiveness of 6-month outpatient CCR for secondary
      prevention after transient ischemic attack or mild, nondisabling stroke. This
      article presents risk factors. A future article will discuss psychological
      outcomes. METHODS: Consecutive consenting subjects having sustained a transient
      ischemic attack or mild, nondisabling stroke within the previous 12 months (mean,
      11.5 weeks; event-to-CCR entry) with >=1 vascular risk factor, were recruited
      from a stroke prevention clinic providing usual care. We measured 6-month CCR
      outcomes following a prospective cohort design. RESULTS: Of 110 subjects
      recruited from January 2005 to April 2006, 100 subjects (mean age, 64.9 years; 46
      women) entered and 80 subjects completed CCR. We obtained favorable, significant
      intake-to-exit changes in: aerobic capacity (+31.4%; P<0.001), total cholesterol
      (-0.30 mmol/L; P=0.008), total cholesterol/high-density lipoprotein (-11.6%;
      P<0.001), triglycerides (-0.27 mmol/L; P=0.003), waist circumference (-2.44 cm;
      P<0.001), body mass index (-0.53 kg/m(2); P=0.003), and body weight (-1.43 kg;
      P=0.001). Low-density lipoprotein (-0.24 mmol/L), high-density lipoprotein (+0.06
      mmol/L), systolic (-3.21 mm Hg) and diastolic (-2.34 mm Hg) blood pressure
      changed favorably, but nonsignificantly. A significant shift toward nonsmoking
      occurred (P=0.008). Compared with intake, 11 more individuals (25.6% increase)
      finished CCR in the lowest-mortality risk category of the Duke Treadmill Score
      (P<0.001). CONCLUSIONS: CCR is feasible and effective for secondary prevention
      after transient ischemic attack or mild, nondisabling stroke, offering a
      promising model for vascular protection across chronic disease entities. We know
      of no similar previous investigation, and are now conducting a randomized trial.

PMID- 21940962
TI  - Plasma-type gelsolin is decreased in human blood and cerebrospinal fluid after
      subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) pathophysiology involves
      neurovascular proteolysis and inflammation. How these 2 phenomena are related
      remains unclear. We hypothesize that matrix metalloproteinases (MMPs) mediate the
      depletion of anti-inflammatory plasma-type gelsolin (pGSN). METHODS: We enrolled
      42 consecutive SAH subjects and sampled cerebrospinal fluid (CSF) and blood on
      post-SAH Days 2 to 3, 4 to 5, 6 to 7, and 10 to 14. Control subjects were 20
      consecutive non-SAH hydrocephalus patients with lumbar drains. Enzyme-linked
      immunosorbent assay, Western blotting, and zymography were used to quantify pGSN
      and MMP-9. RESULTS: In CSF, pGSN was lower in SAH compared with control subjects
      on post-SAH Days 2 to 3 (P=0.0007), 4 to 5 (P=0.041), and 10 to 14 (P=0.007). In
      blood, pGSN decreased over time (P=0.001) and was lower in SAH compared with
      control subjects on post-SAH Days 4 to 5 (P=0.037), 6 to 7 (P=0.006), and 10 to
      14 (P=0.006). Western blots demonstrated that SAH CSF had novel bands at 52 and
      46 kDa, representing cleaved pGSN fragments. Gelatin zymography showed that CSF
      MMP-9 was elevated in SAH compared with control subjects. Higher CSF MMP-9
      correlated with lower CSF pGSN on post-SAH Day 7 (r=-0.38; P=0.05). CONCLUSIONS:
      SAH is associated with decreased CSF and blood pGSN and elevated CSF MMP-9. Novel
      cleaved pGSN fragments are present in CSF of SAH subjects, consistent with pGSN
      cleavage by MMPs. Because pGSN is known to inhibit inflammatory mediators, these
      findings suggest that MMPs may reduce pGSN and exacerbate inflammation after SAH.
      Further studies are warranted to investigate the mechanisms underlying MMP-pGSN
      signaling in SAH.

PMID- 21940963
TI  - Fatalism, optimism, spirituality, depressive symptoms, and stroke outcome: a
      population-based analysis.
AB  - BACKGROUND AND PURPOSE: We sought to describe the association of spirituality,
      optimism, fatalism, and depressive symptoms with initial stroke severity, stroke
      recurrence, and poststroke mortality. METHODS: Stroke cases from June 2004 to
      December 2008 were ascertained in Nueces County, TX. Patients without aphasia
      were queried on their recall of depressive symptoms, fatalism, optimism, and
      nonorganizational spirituality before stroke using validated scales. The
      association between scales and stroke outcomes was studied using multiple linear
      regression with log-transformed National Institutes of Health Stroke Scale and
      Cox proportional hazards regression for recurrence and mortality. RESULTS: Six
      hundred sixty-nine patients participated; 48.7% were women. In fully adjusted
      models, an increase in fatalism from the first to third quartile was associated
      with all-cause mortality (hazard ratio, 1.41; 95% CI, 1.06-1.88) and marginally
      associated with risk of recurrence (hazard ratio, 1.35; 95% CI, 0.97-1.88), but
      not stroke severity. Similarly, an increase in depressive symptoms was associated
      with increased mortality (hazard ratio, 1.32; 95% CI, 1.02-1.72), marginally
      associated with stroke recurrence (HR, 1.22; 95% CI, 0.93-1.62), and with a 9.0%
      increase in stroke severity (95% CI, 0.01-18.0). Depressive symptoms altered the
      fatalism-mortality association such that the association of fatalism and
      mortality was more pronounced for patients reporting no depressive symptoms.
      Neither spirituality nor optimism conferred a significant effect on stroke
      severity, recurrence, or mortality. CONCLUSIONS: Among patients who have already
      had a stroke, self-described prestroke depressive symptoms and fatalism, but not
      optimism or spirituality, are associated with increased risk of stroke recurrence
      and mortality. Unconventional risk factors may explain some of the variability in
      stroke outcomes observed in populations and may be novel targets for
      intervention.

PMID- 21940964
TI  - Postcontrast susceptibility-weighted imaging: a novel technique for the detection
      of arteriovenous shunting in vascular malformations of the brain.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to determine the utility of
      postcontrast susceptibility-weighted MRI (PCSWI) in the evaluation of vascular
      malformations of the brain (BVM). METHODS: We retrospectively evaluated PCSWI and
      digital subtraction angiography data from 16 consecutive patients with known or
      suspected BVM, which had been entered into a prospectively maintained database
      during a 1-year period. There had been no intervening treatment or change in
      patients' symptoms between the PCSWI and digital subtraction angiography studies.
      The use of PCSWI in the detection of arteriovenous shunting was compared with
      that of routine noncontrast susceptibility-weighted imaging, time-of-flight MR
      angiography, and contrast-enhanced MR angiography using digital subtraction
      angiography results as the reference standard. The presence of arteriovenous
      shunting in PCSWI or susceptibility-weighted imaging sequences was defined by the
      presence of abnormal signal hyperintensity in the venous structures adjacent to
      the BVM. RESULTS: A total of 17 BVMs were identified by digital subtraction
      angiography (9 newly diagnosed arteriovenous malformations, 3 dural arteriovenous
      fistulas, 4 treated arteriovenous malformations with residual arteriovenous
      shunting, and 1 complex developmental venous anomaly). PCSWI was 100% sensitive
      and 100% specific with 100% positive predictive value and 100% negative
      predictive value for the detection of arteriovenous shunting in these BVMs. The
      PCSWI/susceptibility-weighted imaging signal intensity ratio in the most
      prominent early draining venous structure was 1.2+/-0.32. CONCLUSIONS: PCSWI
      appears to be superior to susceptibility-weighted imaging, time-of-flight MR
      angiography, and contrast-enhanced MR angiography in detecting arteriovenous
      shunting in BVMs and may be useful in the initial diagnosis and follow-up of
      patients with BVMs.

PMID- 21940965
TI  - Letter by Iosa et al regarding article, "Reliability and validity of bilateral
      ankle accelerometer algorithms for activity recognition and walking speed after
      stroke".

PMID- 21940966
TI  - Neighborhood disadvantage and ischemic stroke: the Cardiovascular Health Study
      (CHS).
AB  - BACKGROUND AND PURPOSE: Neighborhood characteristics may influence the risk of
      stroke and contribute to socioeconomic disparities in stroke incidence. The
      objectives of this study were to examine the relationship between neighborhood
      socioeconomic status and incident ischemic stroke and examine potential mediators
      of these associations. METHODS: We analyzed data from 3834 whites and 785 blacks
      enrolled in the Cardiovascular Health Study, a multicenter, population-based,
      longitudinal study of adults ages>=65 years from 4 US counties. The primary
      outcome was adjudicated incident ischemic stroke. Neighborhood socioeconomic
      status was measured using a composite of 6 census tract variables. Race
      stratified multilevel Cox proportional hazard models were constructed adjusted
      for sociodemographic, behavioral, and biological risk factors. RESULTS: Among
      whites, in models adjusted for sociodemographic characteristics, stroke hazard
      was significantly higher among residents of neighborhoods in the lowest compared
      with the highest neighborhood socioeconomic status quartile (hazard ratio, 1.32;
      95% CI, 1.01-1.72) with greater attenuation of the hazard ratio after adjustment
      for biological risk factors (hazard ratio, 1.16; 0.88-1.52) than for behavioral
      risk factors (hazard ratio, 1.30; 0.99-1.70). Among blacks, we found no
      significant associations between neighborhood socioeconomic status and ischemic
      stroke. CONCLUSIONS: Higher risk of incident ischemic stroke was observed in the
      most disadvantaged neighborhoods among whites, but not among blacks. The
      relationship between neighborhood socioeconomic status and stroke among whites
      appears to be mediated more strongly by biological than behavioral risk factors.

PMID- 21940967
TI  - Adverse effects of bone marrow stromal cell treatment of stroke in diabetic rats.
AB  - BACKGROUND AND PURPOSE: Cell therapy with bone marrow stromal cells (BMSCs)
      improves functional recovery after stroke in nondiabetic rats. However, its
      effect on diabetics with stroke is unknown. This study investigated the effect of
      BMSCs on stroke outcome in Type 1 diabetic (T1DM) rats. METHODS: T1DM was induced
      in adult male Wistar rats by injecting streptozotocin. Nondiabetic and T1DM rats
      were subjected to 2 hours of middle cerebral artery occlusion (MCAO), treated
      with or without BMSCs (3*10(6)) at 24 hours after MCAO, and monitored for 14
      days. RESULTS: Functional benefit was not detected in T1DM-MCAO treated with BMSC
      rats compared with corresponding T1DM-MCAO controls. BMSC treatment in T1DM-MCAO
      rats had increased mortality, blood-brain barrier leakage, brain hemorrhage, and
      angiogenesis. Internal carotid artery neointimal formation and cerebral arteriole
      narrowing/occlusion were also observed in T1DM-MCAO+BMSCs rats compared with T1DM
      MCAO controls (P<0.05), but not in nondiabetic stroke rats. We further studied
      the underlying mechanisms responsible for BMSC-induced blood-brain barrier
      leakage and accelerated vascular damage in T1DM-MCAO rats. We found that the
      expression of angiogenin (an angiogenic factor) and ED1 (a marker for
      macrophages) was significantly increased in the T1DM-MCAO+BMSC rats in the
      ischemic brain and internal carotid artery compared with nontreated T1DM-MCAO
      rats, but not in nondiabetic stroke rats. CONCLUSIONS: BMSC therapy in T1DM-MCAO
      rats does not improve functional outcome. On the contrary, it increases blood
      brain barrier leakage and cerebral artery neointimal formation, and
      arteriosclerosis, which possibly is due to increased expression of angiogenin.
      Thus, BMSC treatment starting 24 hours after MCAO may not be beneficial for
      diabetic subjects with stroke.

PMID- 21940968
TI  - Vertebral artery halo sign in patients with stroke: a key clue for the prompt
      diagnosis of giant cell arteritis.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to describe typical
      ultrasonographic findings of vertebral arteries in patients affected by giant
      cell arteritis. METHODS: Color duplex sonography was used to asses the cervical
      arteries within 24 hours from stroke onset in 1237 patients. Vertebral arteritis
      was considered if concentric, homogeneous, and smooth hypoechogenic mural
      thickening (the so-called halo sign) was present in at least 1 cervical segment
      of the vertebral artery. If the patient showed such findings, an ultrasound
      examination of the temporal artery was also performed. Patients with probable
      giant cell arteritis were treated with high-dose intravenous methylprednisolone
      in association with antiplatelet therapy. Temporal artery biopsy was carried out
      by a vascular surgeon in the site targeted by the ultrasonographer. RESULTS: Five
      patients were diagnosed as having vertebral arteritis according to ultrasound
      criteria. All of them had initial neurological deficit due to infarctions
      affecting the vertebrobasilar territory. One patient died due to aspiration
      pneumonia, whereas the others were independent at discharge. All patients had a
      positive biopsy for giant cell arteritis. CONCLUSIONS: Vertebral artery
      involvement in giant cell arteritis may be suspected by color duplex sonography.
      This fact would allow a prompt diagnosis and treatment of this otherwise fatal
      disease. Because duplex ultrasonography is a usual test performed on patients
      with stroke, the recognition of the halo sign in vertebral arteries may be of
      crucial interest in selected cases.

PMID- 21940969
TI  - Letter by Rodriguez-Garcia and Rodriguez-Garcia [corrected] regarding article,
      "Vascular contributions to cognitive impairment and dementia: a statement for
      healthcare professionals from the American Heart Association/American Stroke
      Association".

PMID- 21940971
TI  - Presence of intracranial artery calcification is associated with mortality and
      vascular events in patients with ischemic stroke after hospital discharge: a
      cohort study.
AB  - BACKGROUND AND PURPOSE: Although intracranial artery calcification (IAC) has been
      reported to be a risk factor for ischemic stroke, the prognostic implications of
      IAC in stroke outcome are unknown. The purpose of this study was to determine the
      association between IAC and risk of vascular events and death in patients with
      stroke after hospital discharge. METHODS: All patients with ischemic stroke over
      a 1-year period were included (n=302). IAC, assessed by multidetector CT, was
      defined as hyperdense foci (peak density>130 Hounsfield units) and assessed in
      the 7 major cerebral arteries. The IAC scores ranged from 0 (no calcification) to
      7. Follow-up information on major clinical events (including fatal or nonfatal
      ischemic stroke, cardiac and peripheral artery events, and all-cause death) was
      obtained by means of a structured phone interview. RESULTS: IAC was present in
      260 patients (83%). With a mean follow-up of 773+/-223 days, 88 major clinical
      events occurred in 67 patients (22%): 45 new ischemic vascular events (ischemic
      stroke: n=22; cardiac event: n=15; peripheral artery event: n=8) and 43 deaths
      from any cause. Patients with the highest IAC scores had significantly higher
      rates of death and vascular events than those with the lowest IAC scores (log
      rank test, P=0.029). In the Cox proportional hazards regression model, the IAC
      score was significantly associated with major clinical events (hazard ratio,
      1.34; 95% CI, 1.11-1.61; P=0.002). CONCLUSIONS: In patients with ischemic stroke,
      IAC detection may constitute a simple marker of a high risk of future major
      clinical events.

PMID- 21940970
TI  - Siblings with ischemic stroke study: results of a genome-wide scan for stroke
      loci.
AB  - BACKGROUND AND PURPOSE: Ischemic stroke has a strong familial component to risk.
      The Siblings With Ischemic Stroke Study (SWISS) is a genome-wide, family-based
      analysis that included use of imputed genotypes. The Siblings With Ischemic
      Stroke Study was conducted to examine the associations between single-nucleotide
      polymorphisms (SNPs) and risk of stroke and stroke subtypes within pairs.
      METHODS: The Siblings With Ischemic Stroke Study enrolled 312 probands with
      ischemic stroke from 70 US and Canadian centers. Affected siblings were
      ascertained by centers and confirmed by central record review; unaffected
      siblings were ascertained by telephone contact. Ischemic stroke was subtyped
      according to Trial of Org 10172 in Acute Stroke Treatment criteria. Genotyping
      was performed with an Illumina 610 quad array (probands) and an Illumina linkage
      V array (affected siblings). SNPs were imputed by using 1000 Genomes Project data
      and MACH software. Family-based association analyses were conducted by using the
      sibling transmission-disequilibrium test. RESULTS: For all pairs, the correlation
      of age at stroke within pairs of affected siblings was r=0.83 (95% CI, 0.78-0.86;
      P<2.2*10(-16)). The correlation did not differ substantially by subtype. The
      concordance of stroke subtypes among affected pairs was 33.8% (kappa=0.13;
      P=5.06*10(-4)) and did not differ by age at stroke in the proband. Although no
      SNP achieved genome-wide significance for risk of ischemic stroke, there was
      clustering of the most associated SNPs on chromosomes 3p (neuronal nitric oxide
      synthase) and 6p. CONCLUSIONS: Stroke subtype and age at stroke in affected
      sibling pairs exhibit significant clustering. No individual SNP reached genome
      wide significance. However, 2 promising candidate loci were identified, including
      1 that contains neuronal nitric oxide synthase, although these risk loci warrant
      further examination in larger sample collections.

PMID- 21940972
TI  - Blood-brain barrier breakdown in acute and chronic cerebrovascular disease.
AB  - Disruptions of the blood-brain barrier (BBB) and edema formation both play key
      roles in the development of neurological dysfunction in acute and chronic
      cerebral ischemia. Animal studies have revealed the molecular cascades that are
      initiated with hypoxia/ischemia in the cells forming the neurovascular unit and
      that contribute to cell death. Matrix metalloproteinases cause reversible
      degradation of tight junction proteins early after the onset of ischemia, and a
      delayed secondary opening during a neuroinflammatory response occurring from 24
      to 72 hours after. Cyclooxygenases are important in the delayed opening as the
      neuroinflammatory response progresses. An early opening of the BBB within the 3
      hour therapeutic window for tissue-type plasminogen activator can allow it to
      enter the brain and increase the risk of hemorrhage. Chronic hypoxic
      hypoperfusion opens the BBB, which contributes to the cognitive changes seen with
      lacunar strokes and white matter injury in subcortical ischemic vascular disease.
      This review will describe the molecular and cellular events associated with BBB
      disruption and potential therapies directed toward restoring the integrity of the
      neurovascular unit.

PMID- 21940973
TI  - Systemic hematologic status following intraventricular recombinant tissue-type
      plasminogen activator for intraventricular hemorrhage: the CLEAR IVH Study Group.
AB  - BACKGROUND AND PURPOSE: This is the first prospective evaluation of changes in
      systemic hematologic status following administration of intraventricular
      recombinant tissue-type plasminogen activator in patients with intraventricular
      hemorrhage (IVH). METHODS: Laboratory data from subjects enrolled onto the Clot
      Lysis: Evaluating Accelerated Resolution of IVH (CLEAR IVH) Trials were analyzed.
      We analyzed pre- and post- recombinant tissue-type plasminogen activator dosing
      coagulation parameters. Longer-term changes in hematologic status were studied in
      subjects who received the study agent after blood clot in the third/fourth
      ventricles had resolved radiologically. RESULTS: Plasma fibrinogen increased
      significantly in both treatment groups. Dosing did not have a significant impact
      on any systemic coagulation parameters in either treatment group. CONCLUSIONS:
      Intraventricular recombinant tissue-type plasminogen activator is unlikely to
      impact systemic coagulation or to compound the effects of systemic
      anticoagulation for deep venous thrombosis prophylaxis. CLINICAL TRIAL
      REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT00650858.

PMID- 21940974
TI  - Intracranial stenting of subacute symptomatic atherosclerotic occlusion versus
      stenosis.
AB  - BACKGROUND AND PURPOSE: Limited data are available concerning the outcome of
      angioplasty/stenting for subacute atherosclerotic intracranial artery occlusion,
      which is often associated with progressive symptom development in the salvageable
      brain under ischemic threat due to poor collateral blood supply. METHODS: Among
      177 patients who underwent angioplasty and/or stenting for severe symptomatic
      intracranial steno-occlusion, 26 had subacute atherosclerotic intracranial artery
      occlusion. Outcome after stenting (N=22) was assessed according to procedural
      success (return of antegrade flow and residual stenosis<50%), adverse event (any
      stroke or death) rate, and restenosis (>50%) using weighted Cox proportional
      hazards regression in the overall cohort and in separate subgroups. RESULTS:
      Successful recanalization was achieved in 95%. Three adverse events (13.6%)
      occurred among patients undergoing stenting for occlusion, including 2 major
      strokes and 1 nonprocedure-related death. Good outcome (modified Rankin Scale<=2)
      was achieved in 73%. In the overall cohort, no significant difference was
      observed between the occlusion and stenosis groups in terms of the risk of
      adverse events (hazard ratio for the occlusion group, 1.055; 95% CI, 0.29-3.90)
      or the risk of restenosis (hazard ratio for the occlusion group, 1.2; 95% CI,
      0.19-7.72). A trend toward a higher rate of adverse events was observed in older
      age (>65 years), progressive worsening, balloon-expandable stent, and no history
      of a preprocedural P2Y12 assay. CONCLUSIONS: In a cohort of patients undergoing
      angioplasty/stenting for subacute atherosclerotic intracranial artery occlusion,
      no significant difference in the rates of adverse events was observed. However,
      several factors, including age, tended to be associated with a higher event rate.

PMID- 21940975
TI  - Frontal and temporal microbleeds are related to cognitive function: the Radboud
      University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort (RUN DMC)
      Study.
AB  - BACKGROUND AND PURPOSE: Cerebral small vessel disease, including white matter
      lesions and lacunar infarcts, is related to cognitive impairment. Cerebral
      microbleeds (MBs) are increasingly being recognized as another manifestation of
      small vessel disease and are also related to cognitive function. However, it
      remains unclear whether this relation is independent of white matter lesions and
      lacunar infarcts and if location of MB plays a role. We investigated the relation
      between the presence, number, and location of MB and cognitive performance
      adjusted for white matter lesions and lacunar infarcts. METHODS: Presence,
      number, and location of MB were rated on a gradient echo T2*-weighted MRI in 500
      nondemented elderly patients with small vessel disease. Cognitive performance was
      assessed in different domains. Analyses were adjusted for age, sex, education,
      depressive symptoms, total brain volume, white matter lesion volume, and lacunar
      and territorial infarcts. RESULTS: Mean age was 65.6 years (SD 8.8) and 57% were
      male. MBs were present in 10.4% of the participants. Subjects with MBs were
      significantly older, had a higher white matter lesion volume, and more lacunar
      infarcts (P<0.001). Presence and number of MBs were related to global cognitive
      function (beta-0.10, P=0.008; beta-0.20, P=0.002), psychomotor speed (beta-0.10,
      P=0.012; beta-0.19, P=0.006), and attention (beta-0.10, P=0.02; beta-0.205,
      P=0.001). The relations with cognitive performance were mainly driven by frontal,
      temporal, and strictly deep located MB. CONCLUSIONS: Frontal and temporal located
      MBs correlate with cognitive performance in nondemented elderly patients
      independent of coexisting other small vessel disease-related lesions. MBs are
      clinically not silent and may help to understand the role of vascular disease in
      cognitive decline.

PMID- 21940976
TI  - Ethnic and geographic variation in stroke mortality trends.
AB  - BACKGROUND AND PURPOSE: Magnitude, geographic, and ethnic variation in trends in
      stroke within the United States require updating for health services and health
      disparities research. METHODS: Data for stroke were analyzed from the US
      mortality files for 1999 to 2007. Age-adjusted death rates were computed for non
      Hispanic African Americans and European Americans aged >=45 years. RESULTS:
      Between 1999 and 2007, the age-adjusted death rate per 100,000 for stroke
      declined both in African Americans and in European Americans of both genders.
      Among African American females, European American females, and European American
      males, rates declined by at least 2% annually in every division. Among African
      American males, rates declined little in the East and West South Central
      divisions where disparities in trends by urbanization level were found.
      CONCLUSIONS: Between 1999 and 2007, the rate of decline in stroke mortality
      varied by geographic region and ethnic group.

PMID- 21940977
TI  - Identifying the genetic contribution to ischemic stroke: in small steps to
      success.

PMID- 21940978
TI  - Audiologic management of auditory neuropathy spectrum disorder in children: a
      systematic review of the literature.
AB  - PURPOSE: This review summarizes current evidence related to the audiologic
      management of children with auditory neuropathy spectrum disorder (ANSD). METHOD:
      A systematic search of the literature was conducted in 25 electronic databases
      (e.g., PubMed, CINAHL, and ERIC) using key words such as auditory neuropathy,
      auditory neuropathy spectrum disorder, auditory neuropathy/dyssynchrony, and
      hearing loss. Eighteen studies met the inclusion criteria by addressing 1 or more
      of 8 clinical questions. Studies were evaluated for methodological quality, and
      data regarding participant, intervention, and outcome variables are reported.
      RESULTS: Fifteen of the 18 studies addressed the use of cochlear implantation,
      and 4 addressed conventional acoustic amplification. All participants
      demonstrated improved auditory performance; however, all 18 studies were
      considered exploratory, and many had methodological limitations. CONCLUSION: The
      clinical evidence related to intervention for ANSD is at a very preliminary
      stage. Additional research is needed to address the efficacy of acoustic
      amplification and cochlear implantation in children with ANSD and the impact of
      this disorder on developmental outcomes.

PMID- 21940979
TI  - Survey of audiologic service provision to older adults with cochlear implants.
AB  - PURPOSE: This study examined whether audiologists modify practice patterns in
      their provision of cochlear implant (CI) services to older adults and, if so,
      whether the nature of such modifications is consistent across clinical sites.
      METHOD: An online survey was sent to audiologists at CI centers across the United
      States. Questions addressed demographics, candidacy, programming, outcomes
      assessment, rehabilitation, and professional development. RESULTS: Responses were
      obtained from 47 audiologists who provided CI services to older adults. The
      majority of these audiologists did not report modifying CI practice patterns on
      the basis of age. Counseling appeared to be an exception: Audiologists reported
      that both the content and delivery of information were modified for older adults.
      Specific to CI candidacy with older adults, under half of the respondents
      indicated that assessing an older adult's cognitive status was part of their
      clinical protocol. CONCLUSION: The audiologists who responded to the survey
      acknowledged issues related to aging when providing CI services to older adults.
      Despite this acknowledgment, the results of the survey suggest a gap in how age
      related issues are incorporated into CI service provision. Continued discussion
      as to how CI services can be optimized for older adults is needed.

PMID- 21940980
TI  - Impact of co-occurring birth defects on the timing of newborn hearing screening
      and diagnosis.
AB  - PURPOSE: Early detection of hearing loss in all newborns and timely intervention
      are critical to children's cognitive, verbal, behavioral, and social development.
      The initiation of appropriate early intervention services before 6 months of age
      can prevent or reduce negative developmental consequences. The purpose of this
      study was to assess, using large, population-based registries, the effect of co
      occurring birth defects (CBDs) on the timing and overall rate of hearing
      screening and diagnosis. METHOD: The authors linked statewide data from newborn
      hearing screenings, a birth defects registry, and birth certificates to assess
      the timeliness of newborn hearing screening and diagnosis of hearing loss (HL)
      for infants with and without CBDs in 485 children with confirmed HL. RESULTS:
      Nearly one third (31.5%) of children with HL had 1 or more CBDs. The presence of
      CBDs prolonged the time of the initial infant hearing screening, which
      contributed to further delays in the subsequent diagnosis of HL. CONCLUSIONS:
      Better coordination of HL assessment into treatment plans for children with CBDs
      may enable earlier diagnosis of HL and provide opportunities for intervention
      that will affect long-term developmental outcomes for these children.

PMID- 21940981
TI  - Gabapentin for tinnitus: a systematic review.
AB  - PURPOSE: The main aim of this study was to assess the effect of gabapentin on
      tinnitus via a systematic review. METHOD: An electronic search of literature as
      well as a hand search were conducted. Only double-blind randomized controlled
      trials (RCTs) that met all of the inclusion criteria were included in this
      review. The Cochrane Collaboration tool for risk of bias assessment was used to
      investigate the validity of the included studies. Meta-analysis was not
      appropriate due to inadequate details in reporting the data in the included
      studies. Hence, qualitative synthesis and interpretation of the data were carried
      out. RESULTS: Two studies that met the inclusion criteria were included in the
      review. Fourteen studies were excluded. There were substantive within-study
      clinical heterogeneities with regard to the baseline tinnitus handicap scores,
      duration of tinnitus, and severity of hearing loss in the included double-blind
      RCTs. CONCLUSION: The authors of both studies reported that gabapentin was not
      superior to placebo in their primary outcomes. However, following the assessment
      of risk of bias and within-study clinical heterogeneities, this review concludes
      that there is insufficient evidence regarding the effect of gabapentin on
      tinnitus.

PMID- 21940982
TI  - Effects of transient noise reduction algorithms on speech intelligibility and
      ratings of hearing aid users.
AB  - PURPOSE: The goal of this study was to assess the functional utility of transient
      noise reduction (TNR) algorithms available in hearing aids via speech
      intelligibility and user preferences. METHOD: Two pairs of hearing aids, 1 pair
      each from Siemens and Unitron, were programmed for 17 hearing impaired
      individuals after a hearing evaluation. Intelligibility was measured for each
      participant for sentences presented in quiet, with 2 types of transient noise,
      multitalker babble, and in a combination of each type of transient noise and
      multitalker babble. Each condition was tested with TNR activated and TNR
      deactivated in a counterbalanced, single-blinded format. Subjective ratings of
      overall speech understanding, comfort, and sound quality were obtained for each
      condition. RESULTS: A significant improvement in speech intelligibility was
      measured with the TNR activated when speech was presented in multitalker babble,
      in the presence of chair clang transient noises, and when combining these noises.
      Activation of the TNR algorithm did not result in significant improvements for
      any of the subjective ratings. CONCLUSIONS: While improvements were limited to
      certain conditions, specifically those with the chair clang transient and/or
      multitalker babble, TNR appears to offer an incremental step in improving the
      listening experience for hearing aid users.

PMID- 21940984
TI  - Androgen receptor gene polymorphisms and the fat-bone axis in young men and
      women.
AB  - Androgen receptor (AR) CAG(n) (polyglutamine) and GGN(n) (polyglycine) repeat
      polymorphisms determine part of the androgenic effect and may influence
      adiposity. The association of fat mass, and its regional distribution, with the
      AR CAG(n) and GGN(n) polymorphisms was studied in 319 and 78 physically active
      nonsmoker men and women (mean +/- SD: 28.3 +/- 7.6 and 24.8 +/- 6.2 years old,
      respectively). The length of CAG and GGN repeats was determined by polymerase
      chain reaction and fragment analysis, and confirmed by DNA sequencing of selected
      samples. Men were grouped as CAG short (CAG(S)) if harboring repeat lengths <=
      21, the rest as CAG long (CAG(L)). The corresponding cutoff CAG number for women
      was 22. GGN was considered short (GGN(S)) if GGN <= 23, the rest as GGN long
      (GGN(L)). No association between AR polymorphisms and adiposity or the hormonal
      variables was observed in men. Neither was there a difference in the studied
      variables between men harboring CAG(L) + GGN(L),CAG(S) + GGN(S),CAG(S) + GGN(L),
      and CAG(L) + GGN(S) combinations. However, in women, GGN(n) was linearly related
      to the percentage of body fat (r = 0.30, P < .05), the percentage of fat in the
      trunk (r = 0.28, P < .05), serum leptin concentration (r = 0.40, P < .05), and
      serum osteocalcin concentration (r = 0.32, P < .05). In men, free testosterone
      was inversely associated with adiposity and serum leptin concentration, and
      positively with osteocalcin, even after accounting for differences in CAG(n),
      GGN(n), or both. In summary, this study shows that the AR repeat polymorphism has
      little influence on absolute and relative fat mass or its regional distribution
      in physically active men. In young women, GGN length is positively associated
      with adiposity, leptin, and osteocalcin.

PMID- 21940983
TI  - Is measured hearing aid benefit affected by seeing baseline outcome questionnaire
      responses?
AB  - PURPOSE: To determine whether hearing aid outcome measured by the Hearing
      Handicap Inventory (HHI) for the Elderly/Adults (Newman, Weinstein, Jacobson, &
      Hug, 1990; Ventry & Weinstein, 1982) is differentially affected by informed vs.
      blind administration of the postfitting questionnaire. METHOD: Participants
      completed the HHI at their hearing aid evaluation and again at their hearing aid
      follow-up visit. At follow-up, half received a clean HHI form (blind
      administration), whereas the remainder responded on their original form (informed
      administration) and could thus base their follow-up responses on those they gave
      at the hearing aid evaluation. RESULTS: The data show that for the population
      examined here, informed administration of the follow-up HHI did not yield a
      different outcome to blind administration of the follow-up HHI. This was not
      influenced by past hearing aid use, age of the participant, or the duration of
      time between baseline questionnaire completion and follow-up completion.
      CONCLUSION: These data suggest that completion of follow-up questionnaires in
      either informed or blind format will have little impact on HHI responses, most
      likely because of the many other factors that combined to influence hearing aid
      outcome.

PMID- 21940985
TI  - Effects of chronic stress on penile corpus cavernosum of rats.
AB  - The objective of this study was to investigate structural changes in the  penile
      corpus cavernosum of prepubertal chronically stressed rats. Eight  Wistar rats
      were assigned into the stress group (SG) and were submitted to 2  hours of tube
      restraint daily, from the fourth to the ninth week of life.  Another 7 rats were
      used as the control group (CG). All animals were weighed  weekly. At day 64,
      animals were sacrificed by anesthetic overdose, blood was  collected for
      testosterone concentration by radioimmunoassay, and penis and  adrenal were
      collected. Adrenal mass index and testosterone serum levels were  used to assess
      the efficacy of the stress stimulus. The surface density of  connective tissue
      and smooth muscle fibers of corpus cavernosum were measured  on Masson trichromic
      stained slices. Picrosirius red-stained  slices were assessed under polarized
      light for different types of collagen.  The Student's t test was applied for mean
      comparisons, with  P < .05 considered significant. Testosterone serum
      concentrations  decreased and adrenal mass index increased, confirming the
      effectiveness of  the stress protocol. Smooth muscle fibers of corpus cavernosum
      decreased from  14.07% (CG) to 8.98% (SG) (P = .02), and connective tissue
      increased  from 53.66% (CG) to 64.47% (SG) (P = .01). Also, there was a higher 
      level of type I collagen in the SG animals compared with the CG. Stress  stimuli
      induced structural changes in the corpus cavernosum of rats suggestive  of penile
      fibrosis, which may play a role in erection dysfunction.

PMID- 21940986
TI  - Subcutaneous implantable testosterone pellets overcome noncompliance in
      adolescents with Klinefelter syndrome.
AB  - For adolescents with hypogonadism, failure to comply with a testosterone 
      replacement therapy (TRT) regimen can be a barrier to obtaining adequate and 
      consistent serum testosterone (T) levels. We evaluated 4 young men with 
      hypogonadism secondary to Klinefelter syndrome to determine if implantable 
      pellets represented a viable treatment option for such patients. Four patients 
      (aged 14-20 years) had previously received TRT but were not compliant.  Patients
      initially received 4 to 10 subcutaneous T pellets with subsequent  doses
      implanted at 3- to 4-month intervals. In all 4 patients, total and free  T levels
      were improved at follow-up, although fluctuations between levels were 
      inconsistent. All patients reported improvement in their energy and 
      concentration, and parents noted improved stability of mood. The mean baseline 
      total T level of 108.3 ng/dL increased in all patients at the time of second 
      pellet implantation. Average total T levels were 325 to 587 ng/dL over the 
      course of therapy. There was significant variability of serum T levels while 
      patients were on therapy. All patients eventually received an increased number 
      of pellets at some point in their care. Subcutaneous implantation of T pellets 
      is a viable option for TRT in young men with Klinefelter syndrome in whom 
      compliance is an issue. However, the requirement for repeat implantation every  3
      months, increased cost of therapy and monitoring, dramatic shifts in serum  total
      and free T concentrations, and seemingly unpredictable response requires  close
      monitoring and careful follow up and suggests this modality of therapy  may not
      be appropriate for a substantial number of hypogonadal patients, but  this
      strategy warrants consideration in noncompliant patients.

PMID- 21940987
TI  - A case of spinal and bulbar muscular atrophy with high-stage and high-Gleason
      Score prostate cancer responded to maximal androgen blockade therapy.
AB  - Spinal and bulbar muscular atrophy is a hereditary motor neuron disease  caused
      by the expansion of CAG triplets in the androgen receptor. Because the  length of
      CAG repeat is inversely related with androgen receptor function,  patients with a
      longer CAG repeat are expected to have a lower incidence of  prostate cancer.
      Here, we report an extremely rare case of high-stage prostate  cancer in a
      patient with spinal and bulbar muscular atrophy, which responded  to maximal
      androgen blockade therapy.

PMID- 21940988
TI  - Association analysis between the tag SNP for sonic hedgehog rs9333613
      polymorphism and male sexual orientation.
AB  - Male sexual orientation has been proposed to have genetic components, but 
      previously suggested candidate genes have all received negative results. The 
      human sonic hedgehog (SHH) gene is located in the 7q36 region, which  was linked
      to male sexual orientation in a previous genome-wide association  study. SHH is
      known to play an important role in embryo patterning,  and there is evidence
      connecting it to sexual orientation. In this study, we  performed an association
      analysis of the SHH tag single nucleotide  polymorphism rs9333613 in 361 subjects
      and 319 Chinese male controls. We find  a significant difference in genotype and
      allele distribution between  identified homosexuals and heterosexual control
      subjects, suggesting that the  SHH gene could potentially be associated with male
      sexual  orientation.

PMID- 21940989
TI  - Tonsillectomy: a cost-effective option for childhood sore throat? Further
      analysis of a randomized controlled trial.
AB  - OBJECTIVE: To compare the estimated cost-effectiveness of childhood
      (adeno)tonsillectomy vs medical therapy for recurrent sore throats from the
      intention-to-treat (ITT) analysis of a randomized controlled trial (RCT) with
      that modeled on the recorded timing of surgical interventions as observed in all
      participants irrespective of their original group allocation. STUDY DESIGN: A
      pragmatic RCT (trial) with a parallel nonrandomized patient preference group
      (cohort) of (adeno)tonsillectomy vs medical therapy. SETTING: Five secondary care
      UK otolaryngology departments. SUBJECTS AND METHODS: Eligible children, aged 4 to
      15 years, were enrolled to the trial (268) or cohort (461) groups. Outcomes
      included sore throat diaries, quality of life, and general practice
      consultations. The RCT protocol ITT analysis was compared with an as-treated
      analysis incorporating the cohort group, modeled to reflect the timing of
      tonsillectomy and the differential switch rates among the original groups.
      RESULTS: In the RCT ITT analysis, tonsillectomy saved 3.5 sore throats, whereas
      the as-treated model suggested an average reduction of more than 8 sore throats
      in 2 years for surgery within 10 weeks of consultation, falling to only 3.5
      twelve months later due to the spontaneous improvement in the medical therapy
      group. CONCLUSION: In eligible UK school-age children, tonsillectomy can save up
      to 8 sore throats at a reasonable cost, if performed promptly. Further
      prospective data collection, accounting for baseline and per-trial preferences
      and choice, is urgently needed.

PMID- 21940990
TI  - Evaluating the applicability of a biodegradable osteosynthesis plating system in
      the management of zygomatico-maxillary complex fractures.
AB  - OBJECTIVE: The present study was undertaken to evaluate and analyze the efficacy
      of bioresorbable plates and screws in internal fixation of zygomatico-maxillary
      complex (ZMC) fractures and to evaluate the incidence of complications associated
      with the procedure. STUDY DESIGN: Case series with planned data collection.
      SETTING: Pt BD Sharma University of Health Sciences. SUBJECT AND METHODS: A total
      of 14 patients with isolated ZMC fractures were included, and exclusion of
      grossly comminuted, pathological, and infected fractures was done. Open reduction
      internal fixation was done with biodegradable plates and screws. All patients
      were reviewed clinically and radiographically at regular follow-up. Occlusion,
      stability of fracture segments, anesthesia or paresthesia of the infraorbital
      nerve region, and various complications were assessed periodically. RESULTS:
      Fourteen patients with 34 fracture sites were included in the study.
      Intraoperatively, there were 2 incidences of screw head fracture. As observed
      clinically, there was complete stability of fracture segments, and no
      maxillomandibular fixation was required postoperatively. Paresthesia of the
      infraorbital nerve was present in 5 patients, but the sensation recovered
      completely in the first 3 months after surgery. The mean pain score was 3 on a
      visual analogue scale. In 1 case, ectropion developed, and dehiscence occurred in
      another patient in the early postoperative period. Postoperative radiographs were
      evaluated for the accuracy of fracture reduction and stability of fixation.
      CONCLUSION: The biodegradable osteosynthesis system exhibits adequate strength
      and has negligible complications. This system is technique sensitive with
      satisfactory results in the management of mild to moderately displaced ZMC
      fractures.

PMID- 21940991
TI  - Revision stapes surgery.
AB  - OBJECTIVES: Surgery for otosclerosis has a highly satisfactory hearing outcome,
      for both the patient and the otologic surgeon. However, subsequent conductive
      hearing loss, dizziness/vertigo, or sound distortion could necessitate revision
      surgery. The aim of the present study is to evaluate the surgical findings and
      hearing outcomes of 84 revision stapes surgeries. STUDY DESIGN: Case series with
      chart review. SETTING: Tertiary referral center. SUBJECTS AND METHODS: At our
      institution, 84 revision cases were performed between 1998 and 2009. Conductive
      hearing loss was the revision indication in 69 cases, severe dizziness/vertigo in
      8 patients, sound distortion in 5 cases, and progressive hearing loss with
      dizziness in 2 patients. Operative findings were noted in every case and
      evaluated separately. RESULTS: Surgical intervention revealed problems related to
      prosthesis in 51 cases, fibrotic bands in 26 cases, adhesions in 13 cases, incus
      necrosis in 15 cases, perilymphatic fistula in 3 cases, intact footplate in 5
      cases, incus-malleus fixation in 2 cases, and reobliteration in 2 cases. Mean
      follow-up period was 19 months (range, 12-53 months). Successful hearing results
      (air-bone gap <10 dB) were reached in 58% of the cases, and satisfactory hearing
      results (air-bone gap <20 dB) were reached in 71% of the cases. CONCLUSIONS: The
      ideal patient for revision stapes surgery is one who benefits from the initial
      surgery but complained of conductive hearing loss. In the present study,
      improvement in pure-tone average was 13.2 dB, and the mean air-bone gap was 9.6
      dB.

PMID- 21940992
TI  - Effects of ovariectomy and estrogen replacement therapy on laryngeal tissue: a
      histopathological experimental animal study.
AB  - OBJECTIVE: To determine the histopathological effect of estrogen deficiency and
      hormone replacement treatment on laryngeal tissue in ovariectomized rats. STUDY
      DESIGN: Animal study. SETTING: The study was conducted at the animal experiment
      laboratory of Marmara University School of Medicine, Istanbul, Turkey. SUBJECTS
      AND METHODS: Six-month-old female Wistar albino rats were divided into the
      following 3 groups (n = 8 per group): sham-operated control, ovariectomized, and
      ovariectomized with estrogen replacement. Rats in the ovariectomized with
      estrogen replacement group received 17 beta-estradiol valerate (200 ug/kg,
      subcutaneously) once a week. Animals were killed after 8 weeks of intervention.
      RESULTS: Significant changes were observed in the ovariectomized group when edema
      in lamina propria, inflammation in squamous, respiratory epithelia and lamina
      propria, pseudostratification, and cilia loss were assessed. Except cilia loss,
      there were no significant differences in the assessments between the sham
      operated control and ovariectomized with estrogen replacement groups.
      CONCLUSIONS: On the basis of histopathological evaluations, it was shown that
      estrogen replacement helped to improve laryngeal changes due to experimentally
      induced menopause.

PMID- 21940993
TI  - Self-regulated alternative splicing at the AHNAK locus.
AB  - AHNAK is a 700-kDa protein involved in cytoarchitecture and calcium signaling. It
      is secondarily reduced in muscle of dysferlinopathy patients and accumulates in
      muscle of calpainopathy patients, both affected by a muscular dystrophy. AHNAK
      directly interacts with dysferlin. This interaction is lost on cleavage of AHNAK
      by the protease calpain 3, explaining the molecular observations in patients.
      Currently, little is known of AHNAK regulation. We describe the self-regulation
      of multiple mRNA transcripts emanating from the AHNAK locus in muscle cells. We
      show that the AHNAK gene consists of a 17-kb exon flanked by multiple small
      exons. This genetic structure is shared by AHNAK2 and Periaxin, which share a
      common ancestor. Two major AHNAK transcripts are differentially expressed during
      muscle differentiation that encode for a small (17-kDa) and a large (700-kDa)
      protein isoform. These proteins interact in the cytoplasm, but the small AHNAK is
      also present in the nucleus. During muscle differentiation the small AHNAK is
      strongly increased, thereby establishing a positive feedback loop to regulate
      mRNA splicing of its own locus. A small 17-kDa isoform of Periaxin similarly
      traffics between the cytoplasm and the nucleus to regulate mRNA splicing. Thus,
      AHNAK constitutes a novel mechanism in post-transcriptional control of gene
      expression.

PMID- 21940994
TI  - gamma-Interferon-regulated chaperone governs human lymphocyte antigen class II
      expression.
AB  - Antigen presentation by human lymphocyte antigen (HLA) class II peptide receptors
      alerts the immune system to infections. In antigen-presenting cells (APCs), HLA
      class II, HLA-DM, and associated invariant chain-encoding genes are exclusively
      regulated by the interferon gamma (IFNgamma)-inducible class II transactivator
      (CIITA). Control of CIITA expression could therefore govern expression of class
      II peptide receptors in the diverse group of APCs. We discovered that elevation
      of the HLA class III region encoded B-associated transcript 3 (BAT3) increases
      and depletion of BAT3 decreases expression of HLA class II, HLA-DM, and invariant
      chain. IFNgamma strongly elevates BAT3 transcription in various tumor cell lines
      and in primary macrophages. BAT3 chaperones the simultaneously IFNgamma-induced
      CIITA. Following IFNgamma-treatment, both CIITA and BAT3 translocate from the
      cytosol to the nucleus. The nuclear import of CIITA mediated by IFNgamma controls
      activation of HLA class II genes. BAT3 is a novel key regulator of components of
      the HLA class II processing pathway. We present a mechanism explaining how
      parallel IFNgamma-mediated regulation of CIITA and of its chaperone BAT3 controls
      the level of components of the HLA class II processing pathway.

PMID- 21940996
TI  - Crucial yet divergent roles of mitochondrial redox state in skeletal muscle vs.
      brown adipose tissue energetics.
AB  - Reduced glutathione (GSH) is the major determinant of redox balance in
      mitochondria and as such is fundamental in the control of cellular bioenergetics.
      GSH is also the most important nonprotein antioxidant molecule in cells.
      Surprisingly, the effect of redox environment has never been examined in skeletal
      muscle and brown adipose tissue (BAT), two tissues that have exceptional dynamic
      range and that are relevant to the development of obesity and related diseases.
      Here, we show that the redox environment plays crucial, yet divergent, roles in
      modulating mitochondrial bioenergetics in skeletal muscle and BAT. Skeletal
      muscle mitochondria were found to naturally have a highly reduced environment
      (GSH/GSSG~46), and this was associated with fairly high (~40%) rates of state 4
      (nonphosphorylating) respiration and decreased reactive oxygen species (ROS)
      emission. The deglutathionylation of uncoupling protein 3 (UCP3) following an
      increase in the reductive potential of mitochondria results in a further increase
      in nonphosphorylating respiration (~20% in situ). BAT mitochondria were found to
      have a much more oxidized status (GSH/GSSG~13) and had basal reactive oxygen
      species emission that was higher (~250% increase in ROS generation) than that in
      skeletal muscle mitochondria. When redox status was subsequently increased (i.e.,
      more reduced), UCP1-mediated uncoupling was more sensitive to GDP inhibition.
      Surprisingly, BAT was found to be devoid of glutaredoxin-2 (Grx2) expression,
      while there was abundant expression in skeletal muscle. Taken together, these
      findings reveal the importance of redox environment in controlling bioenergetic
      functions in both tissues, and the highly unique characteristics of BAT in this
      regard.

PMID- 21940995
TI  - Retinoid receptors trigger neuritogenesis in retinal degenerations.
AB  - Anomalous neuritogenesis is a hallmark of neurodegenerative disorders, including
      retinal degenerations, epilepsy, and Alzheimer's disease. The neuritogenesis
      processes result in a partial reinnervation, new circuitry, and functional
      changes within the deafferented retina and brain regions. Using the light-induced
      retinal degeneration (LIRD) mouse model, which provides a unique platform for
      exploring the mechanisms underlying neuritogenesis, we found that retinoid X
      receptors (RXRs) control neuritogenesis. LIRD rapidly triggered retinal neuron
      neuritogenesis and up-regulated several key elements of retinoic acid (RA)
      signaling, including retinoid X receptors (RXRs). Exogenous RA initiated
      neuritogenesis in normal adult retinas and primary retinal cultures and
      exacerbated it in LIRD retinas. However, LIRD-induced neuritogenesis was partly
      attenuated in retinol dehydrogenase knockout (Rdh12(-/-)) mice and by aldehyde
      dehydrogenase inhibitors. We further found that LIRD rapidly increased the
      expression of glutamate receptor 2 and beta Ca(2+)/calmodulin-dependent protein
      kinase II (betaCaMKII). Pulldown assays demonstrated interaction between
      betaCaMKII and RXRs, suggesting that CaMKII pathway regulates the activities of
      RXRs. RXR antagonists completely prevented and RXR agonists were more effective
      than RA in inducing neuritogenesis. Thus, RXRs are in the final common path and
      may be therapeutic targets to attenuate retinal remodeling and facilitate global
      intervention methods in blinding diseases and other neurodegenerative disorders.

PMID- 21940997
TI  - Hormonal regulation of lateral root development in Arabidopsis modulated by MIZ1
      and requirement of GNOM activity for MIZ1 function.
AB  - Plant organ development is important for adaptation to a changing environment.
      Genetic and physiological studies have revealed that plant hormones play key
      roles in lateral root formation. In this study, we show that MIZU-KUSSEI1 (MIZ1),
      which was identified originally as a regulator of hydrotropism, functions as a
      novel regulator of hormonally mediated lateral root development. Overexpression
      of MIZ1 (MIZ1OE) in roots resulted in a reduced number of lateral roots being
      formed; however, this defect could be recovered with the application of auxin.
      Indole-3-acetic acid quantification analyses showed that free indole-3-acetic
      acid levels decreased in MIZ1OE roots, which indicates that alteration of auxin
      level is critical for the inhibition of lateral root formation in MIZ1OE plants.
      In addition, MIZ1 negatively regulates cytokinin sensitivity on root development.
      Application of cytokinin strongly induced the localization of MIZ1-green
      fluorescent protein to lateral root primordia, which suggests that the inhibition
      of lateral root development by MIZ1 occurs downstream of cytokinin signaling.
      Surprisingly, miz2, a weak allele of gnom, suppressed developmental defects in
      MIZ1OE plants. Taken together, these results suggest that MIZ1 plays a role in
      lateral root development by maintaining auxin levels and that its function
      requires GNOM activity. These data provide a molecular framework for auxin
      dependent organ development in Arabidopsis (Arabidopsis thaliana).

PMID- 21940998
TI  - N-acyl-homoserine lactone confers resistance toward biotrophic and hemibiotrophic
      pathogens via altered activation of AtMPK6.
AB  - Pathogenic and symbiotic bacteria rely on quorum sensing to coordinate the
      collective behavior during the interactions with their eukaryotic hosts. Many
      Gram-negative bacteria use N-acyl-homoserine lactones (AHLs) as signals in such
      communication. Here we show that plants have evolved means to perceive AHLs and
      that the length of acyl moiety and the functional group at the gamma position
      specify the plant's response. Root treatment with the N-3-oxo-tetradecanoyl-L
      homoserine lactone (oxo-C14-HSL) reinforced the systemic resistance to the
      obligate biotrophic fungi Golovinomyces orontii in Arabidopsis (Arabidopsis
      thaliana) and Blumeria graminis f. sp. hordei in barley (Hordeum vulgare) plants.
      In addition, oxo-C14-HSL-treated Arabidopsis plants were more resistant toward
      the hemibiotrophic bacterial pathogen Pseudomonas syringae pv tomato DC3000. Oxo
      C14-HSL promoted a stronger activation of mitogen-activated protein kinases
      AtMPK3 and AtMPK6 when challenged with flg22, followed by a higher expression of
      the defense-related transcription factors WRKY22 and WRKY29, as well as the
      PATHOGENESIS-RELATED1 gene. In contrast to wild-type Arabidopsis and mpk3 mutant,
      the mpk6 mutant is compromised in the AHL effect, suggesting that AtMPK6 is
      required for AHL-induced resistance. Results of this study show that AHLs
      commonly produced in the rhizosphere are crucial factors in plant pathology and
      could be an agronomic issue whose full impact has to be elucidated in future
      analyses.

PMID- 21940999
TI  - Molecular and biochemical basis for stress-induced accumulation of free and bound
      p-coumaraldehyde in cucumber.
AB  - To elucidate the genetic and biochemical regulation of elicitor-induced p
      coumaraldehyde accumulation in plants, we undertook a multifaceted approach to
      characterize the metabolic flux through the phenylpropanoid pathway via the
      characterization and chemical analysis of the metabolites in the p-coumaryl,
      coniferyl, and sinapyl alcohol branches of this pathway. Here, we report the
      identification and characterization of four cinnamyl alcohol dehydrogenases
      (CADs) from cucumber (Cucumis sativus) with low activity toward p-coumaraldehyde
      yet exhibiting significant activity toward other phenylpropanoid
      hydroxycinnamaldehydes. As part of this analysis, we identified and characterized
      the activity of a hydroxycinnamoyl-coenzyme A:shikimate hydroxycinnamoyl
      transferase (HCT) capable of utilizing shikimate and p-coumaroyl-coenzyme A to
      generate p-coumaroyl shikimate. Following pectinase treatment of cucumber, we
      observed the rapid accumulation of p-coumaraldehyde, likely the result of low
      aldehyde reductase activity (i.e. alcohol dehydrogenase in the reverse reaction)
      of CsCAD enzymes on p-coumaraldehyde. In parallel, we noted a concomitant
      reduction in the activity of CsHCT. Taken together, our findings support the
      hypothesis that the up-regulation of the phenylpropanoid pathway upon abiotic
      stress greatly enhances the overall p-coumaryl alcohol branch of the pathway. The
      data presented here point to a role for CsHCT (as well as, presumably, p
      coumarate 3-hydroxylase) as a control point in the regulation of the coniferyl
      and sinapyl alcohol branches of this pathway. This mechanism represents a
      potentially evolutionarily conserved process to efficiently and quickly respond
      to biotic and abiotic stresses in cucurbit plants, resulting in the rapid
      lignification of affected tissues.

PMID- 21941000
TI  - The Arabidopsis purple acid phosphatase AtPAP10 is predominantly associated with
      the root surface and plays an important role in plant tolerance to phosphate
      limitation.
AB  - Induction of secreted acid phosphatase (APase) is a universal response of higher
      plants to phosphate (Pi) limitation. These enzymes are thought to scavenge Pi
      from organophosphate compounds in the rhizosphere and thus to increase Pi
      availability to plants when Pi is deficient. The tight association of secreted
      APase with the root surface may make plants more efficient in the utilization of
      soil Pi around root tissues, which is present in organophosphate forms. To date,
      however, no systematic molecular, biochemical, and functional studies have been
      reported for any of the Pi starvation-induced APases that are associated with the
      root surface after secretion. In this work, using genetic and molecular
      approaches, we identified Arabidopsis (Arabidopsis thaliana) Purple Acid
      Phosphatase10 (AtPAP10) as a Pi starvation-induced APase that is predominantly
      associated with the root surface. The AtPAP10 protein has phosphatase activity
      against a variety of substrates. Expression of AtPAP10 is specifically induced by
      Pi limitation at both transcriptional and posttranscriptional levels. Functional
      analyses of multiple atpap10 mutant alleles and overexpressing lines indicated
      that AtPAP10 plays an important role in plant tolerance to Pi limitation. Genetic
      manipulation of AtPAP10 expression may provide an effective means for engineering
      new crops with increased tolerance to Pi deprivation.

PMID- 21941001
TI  - The tomato MADS-box transcription factor RIPENING INHIBITOR interacts with
      promoters involved in numerous ripening processes in a COLORLESS NONRIPENING
      dependent manner.
AB  - Fruit ripening is a complex developmental process responsible for the
      transformation of the seed-containing organ into a tissue attractive to seed
      dispersers and agricultural consumers. The coordinated regulation of the
      different biochemical pathways necessary to achieve this change receives
      considerable research attention. The MADS-box transcription factor RIPENING
      INHIBITOR (RIN) is an essential regulator of tomato (Solanum lycopersicum) fruit
      ripening but the exact mechanism by which it influences the expression of
      ripening-related genes remains unclear. Using a chromatin immunoprecipitation
      approach, we provide evidence that RIN interacts with the promoters of genes
      involved in the major pathways associated with observed and well-studied ripening
      phenotypes and phenomena, including the transcriptional control network involved
      in overall ripening regulation, ethylene biosynthesis, ethylene perception,
      downstream ethylene response, cell wall metabolism, and carotenoid biosynthesis.
      Furthermore, in the cases of ethylene and carotenoid biosynthesis, RIN interacts
      with the promoters of genes encoding rate-limiting activities. We also show that
      RIN recruitment to target loci is dependent on a normally functioning allele at
      the ripening-specific transcription factor COLORLESS NONRIPENING gene locus,
      further clarifying the relationship between these two ripening regulators.

PMID- 21941002
TI  - Spatiotemporal analysis of copper homeostasis in Populus trichocarpa reveals an
      integrated molecular remodeling for a preferential allocation of copper to
      plastocyanin in the chloroplasts of developing leaves.
AB  - Plastocyanin, which requires copper (Cu) as a cofactor, is an electron carrier in
      the thylakoid lumen and essential for photoautotrophic growth of plants. The Cu
      microRNAs, which are expressed during Cu deprivation, down-regulate several
      transcripts that encode for Cu proteins. Since plastocyanin is not targeted by
      the Cu microRNAs, a cofactor economy model has been proposed in which plants
      prioritize Cu for use in photosynthetic electron transport. However, defects in
      photosynthesis are classic symptoms of Cu deprivation, and priorities in Cu
      cofactor delivery have not been determined experimentally. Using hydroponically
      grown Populus trichocarpa (clone Nisqually-1), we have established a
      physiological and molecular baseline for the response to Cu deficiency. An
      integrated analysis showed that Cu depletion strongly reduces the activity of
      several Cu proteins including plastocyanin, and consequently, photosynthesis and
      growth are decreased. Whereas plastocyanin mRNA levels were only mildly affected
      by Cu depletion, this treatment strongly affected the expression of other Cu
      proteins via Cu microRNA-mediated transcript down-regulation. Polyphenol oxidase
      was newly identified as Cu regulated and targeted by a novel Cu microRNA,
      miR1444. Importantly, a spatiotemporal analysis after Cu resupply to previously
      depleted plants revealed that this micronutrient is preferentially allocated to
      developing photosynthetic tissues. Plastocyanin and photosynthetic electron
      transport efficiency were the first to recover after Cu addition, whereas
      recovery of the other Cu-dependent activities was delayed. Our findings lend new
      support to the hypothesis that the Cu microRNAs serve to mediate a prioritization
      of Cu cofactor use. These studies also highlight poplar as an alternative
      sequenced model for spatiotemporal analyses of nutritional homeostasis.

PMID- 21941003
TI  - Death receptor 5 signaling promotes hepatocyte lipoapoptosis.
AB  - Nonalcoholic steatohepatitis is characterized by hepatic steatosis, elevated
      levels of circulating free fatty acids (FFA), endoplasmic reticulum (ER) stress,
      and hepatocyte lipoapoptosis. Tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL) death receptor 5 (DR5) is significantly elevated in patients with
      nonalcoholic steatohepatitis, and steatotic hepatocytes demonstrate increased
      sensitivity to TRAIL-mediated cell death. Nonetheless, a role for TRAIL and/or
      DR5 in mediating lipoapoptotic pathways is unexplored. Here, we examined the
      contribution of DR5 death signaling to lipoapoptosis by free fatty acids. The
      toxic saturated free fatty acid palmitate induces an increase in DR5 mRNA and
      protein expression in Huh-7 human hepatoma cells leading to DR5 localization into
      lipid rafts, cell surface receptor clustering with subsequent recruitment of the
      initiator caspase-8, and ultimately cellular demise. Lipoapoptosis by palmitate
      was not inhibited by a soluble human recombinant DR5-Fc chimera protein
      suggesting that DR5 cytotoxic signaling is ligand-independent. Hepatocytes from
      murine TRAIL receptor knock-out mice (DR(-/-)) displayed reduced palmitate
      mediated lipotoxicity. Likewise, knockdown of DR5 or caspase-8 expression by
      shRNA technology attenuated palmitate-induced Bax activation and apoptosis in Huh
      7 cells, without altering induction of ER stress markers. Similar observations
      were verified in other cell models. Finally, knockdown of CHOP, an ER stress
      mediated transcription factor, reduced DR5 up-regulation and DR5-mediated caspase
      8 activation upon palmitate treatment. Collectively, these results suggest that
      ER stress-induced CHOP activation by palmitate transcriptionally up-regulates
      DR5, likely resulting in ligand-independent cytotoxic signaling by this death
      receptor.

PMID- 21941005
TI  - Effect of creatine supplementation on jumping performance in elite volleyball
      players.
AB  - Jump height is a critical aspect of volleyball players' blocking and attacking
      performance. Although previous studies demonstrated that creatine monohydrate
      supplementation (CrMS) improves jumping performance, none have yet evaluated its
      effect among volleyball players with proficient jumping skills. We examined the
      effect of 4 wk of CrMS on 1 RM spike jump (SJ) and repeated block jump (BJ)
      performance among 12 elite males of the Sherbrooke University volleyball team.
      Using a parallel, randomized, double-blind protocol, participants were
      supplemented with a placebo or creatine solution for 28 d, at a dose of 20 g/d in
      days 1-4, 10 g/d on days 5-6, and 5 g/d on days 7-28. Pre- and
      postsupplementation, subjects performed the 1 RM SJ test, followed by the
      repeated BJ test (10 series of 10 BJs; 3 s interval between jumps; 2 min recovery
      between series). Due to injuries (N = 2) and outlier data (N = 2), results are
      reported for eight subjects. Following supplementation, both groups improved SJ
      and repeated BJ performance. The change in performance during the 1 RM SJ test
      and over the first two repeated BJ series was unclear between groups. For series
      3-6 and 7-10, respectively, CrMS further improved repeated BJ performance by 2.8%
      (likely beneficial change) and 1.9% (possibly beneficial change), compared with
      the placebo. Percent repeated BJ decline in performance across the 10 series did
      not differ between groups pre- and postsupplementation. In conclusion, CrMS
      likely improved repeated BJ height capability without influencing the magnitude
      of muscular fatigue in these elite, university-level volleyball players.

PMID- 21941004
TI  - Germline BAP1 mutation predisposes to uveal melanoma, lung adenocarcinoma,
      meningioma, and other cancers.
AB  - OBJECTIVE: To investigate the potential contribution of germline sequence
      alterations in the BAP1 gene in uveal melanoma (UM) patients with possible
      predisposition to hereditary cancer. DESIGN: A total of 53 unrelated UM patients
      with high risk for hereditary cancer and five additional family members of one
      proband were studied. Mutational screening was carried out by direct sequencing.
      RESULTS: Of the 53 UM patients studied, a single patient was identified with a
      germline BAP1 truncating mutation, c. 799 C->T (p.Q267X), which segregated in
      several family members and was associated with UM and other cancers. Biallelic
      inactivation of BAP1 and decreased BAP1 expression were identified in the UM,
      lung adenocarcinoma and meningioma tumours from three family members with this
      germline BAP1 mutation. Germline BAP1 variants of uncertain significance, likely
      non-pathogenic, were also identified in two additional UM patients. CONCLUSION:
      This study reports a novel hereditary cancer syndrome caused by a germline BAP1
      mutation that predisposes patients to UM, lung carcinoma, meningioma, and
      possibly other cancers. The results indicate that BAP1 is the candidate gene in
      only a small subset of hereditary UM, suggesting the contribution of other
      candidate genes.

PMID- 21941007
TI  - The effect of a second runner on pacing strategy and RPE during a running time
      trial.
AB  - PURPOSE: The aim of this study was to examine performance, pacing strategy and
      perception of effort during a 5 km time trial while running with or without the
      presence of another athlete. METHODS: Eleven nonelite male athletes participated
      in five 5 km time trials: two self-paced, maximal effort trials performed at the
      start and end of the study, and three trials performed in the presence of a
      second runner. In the three trials, the second runner ran either in front of the
      subject, behind the subject, or next to the subject. Performance times, heart
      rate, RPE, and a subjective assessment of the effect of the second runner on the
      athlete's performance were recorded during each of the trials. RESULTS: There was
      no significant difference in performance times, heart rate or RPE between any of
      the five trials. Running speed declined from the 1st to the 4th kilometer and
      then increased for the last kilometer in all five trials. Following the
      completion of all trials, 9 of the 11 subjects perceived it to be easier to
      complete the 5 km time trial with another runner in comparison with running
      alone. CONCLUSIONS: While the athletes perceived their performance to be improved
      by the presence of another runner, their pacing strategy, running speed, heart
      rate and RPE were not significantly altered. These findings indicate that an
      athlete's subconscious pacing strategy is robust and is not altered by the
      presence of another runner.

PMID- 21941009
TI  - Hydration status in adolescent judo athletes before and after training in the
      heat.
AB  - Adolescent judo athletes who train in tropical climates may be in a persistent
      state of dehydration because they frequently restrict fluids during daily
      training sessions to maintain or reduce their body weight and are not given
      enough opportunities to drink. PURPOSE: Determine the body hydration status of
      adolescent judo athletes before, immediately after, and 24 h after (24H) a
      training session and document sweat Na+ loss and symptoms of dehydration.
      METHODS: Body mass and urine color and specific gravity (USG) were measured
      before, after, and 24 h after a training session in a high-heat-stress
      environment (29.5 +/- 1.0 degrees C; 77.7 +/- 6.1% RH) in 24 adolescent athletes.
      Sweat sodium loss was also determined. A comparison was made between mid-pubertal
      (MP) and late pubertal (LP) subjects. RESULTS: The majority of the subjects
      started training with a significant level of dehydration. During the training
      session, MP subjects lost 1.3 +/- 0.8% of their pretraining body mass whereas LP
      subjects lost 1.9 +/- 0.5% (P < .05). Sweat sodium concentration was 44.5 +/-
      23.3 mmol/L. Fluid intake from a water fountain was minimal. Subjects reported
      symptoms of dehydration during the session, which in some cases persisted
      throughout the night and the next day. The 24H USG was 1.028 +/- 0.004 and 1.027
      +/- 0.005 g/mL for MP and LP, respectively. CONCLUSIONS: Adolescent judo athletes
      arrive to practice with a fluid deficit, do not drink enough during training, and
      experience symptoms of dehydration, which may compromise the quality of training
      and general well-being.

PMID- 21941010
TI  - Short-term hematological effects upon completion of a four-week simulated
      altitude camp.
AB  - Hemoglobin mass (tHb) is considered to be a main factor for sea-level performance
      after "live high-train low" (LHTL) altitude training, but little research has
      focused on the persistence of tHb following cessation of altitude exposure. The
      aim of the case study was to investigate short-term effects of various
      hematological measures including tHb upon completion of a simulated altitude
      camp. Five female cyclists spent 26 nights at simulated altitude (LHTL, 16.6 +/-
      0.4 h/d, 3000 m in an altitude house) where tHb was measured at baseline, at
      cessation of the camp, and 9 d thereafter. Venous blood measures (hemoglobin
      concentration, hematocrit, %reticulocytes, serum erythropoietin, ferritin,
      lactate dehydrogenase, and haptoglobin) were determined at baseline; on day 21
      during LHTL; and at days 2, 5, and 9 after LHTL. Hemoglobin mass increased by
      5.5% (90% confidence limits [CL] 2.5 to 8.5%, very likely) after the LHTL
      training camp. At day 9 after simulated LHTL, tHb decreased by 3.0% (90%CL -5.1
      to -1.0%, likely). There was a substantial decrease in serum EPO (-34%, 90%CL -50
      to -12%) at 2 d after return to sea level and a rise in ferritin (23%, 90%CL 3 to
      46%) coupled with a decrease in %reticulocytes (-23%, 90%CL -34 to -9%) between
      day 5 and 9 after LHTL. Our findings show that following a hypoxic intervention
      with a beneficial tHb outcome, there may be a high probability of a rapid tHb
      decrease upon return to normoxic conditions. This highlights a rapid component in
      red-cell control and may have implications for the appropriate timing of altitude
      training in relation to competition.

PMID- 21941011
TI  - Resistance exercise inter-set cooling strategy: effect on performance and muscle
      damage.
AB  - PURPOSE: To compare the effect of inter-set cooling and no cooling during
      resistance exercise (RE) on the total repetitions and select muscle damage
      biomarker responses. METHODS: Sixteen healthy men volunteered to participate in
      this study and were randomly assigned to Cooling (n = 8) or Control (n = 8)
      groups. They performed a RE protocol consisting of four sets of biceps curl at
      80% of 1RM. The cooling group received the application of wet bags of ice during
      each interest rest interval (Cooling), while the Control realized the same
      protocol without ice application. Exercise was performed to voluntary fatigue and
      the numbers of repetitions per set were recorded. Subjects provided blood samples
      before and at 24, 48, and 72 h following RE to evaluate serum CK activity and
      myoglobin concentration. RESULTS: The Cooling group produced a greater number of
      repetitions (approx. 21%) than did the Control, but there were no differences in
      serum CK activity and myoglobin responses between the groups. CONCLUSION:
      Incorporating inter-set external cooling augments the number of repetitions per
      set during RE without inducing an additional muscle damage biomarker response.

PMID- 21941012
TI  - Influence of sodium bicarbonate on performance and hydration in lightweight
      rowing.
AB  - PURPOSE: The effect of sodium bicarbonate (NaHCO3) ingestion on prerace hydration
      status and on 2000 m ergometer performance in elite lightweight rowers was
      examined using a randomized, cross-over, double-blinded design. METHODS: To
      simulate body mass (BM) management strategies common to lightweight rowing,
      oarsmen reduced BM by approx. 4% in the 24 h preceding the trials, and, in the 2
      h before performance, undertook nutritional recovery consisting of mean 43.2
      kJ/kg, 2.2 g of CHO per kilogram, 31.8 mg of Na+ per kilogram, 24.3 mL of H2O per
      kilogram, and NaHCO3 (0.3 g of NaHCO3 per kilogram BM) or placebo (PL; 0.15 g of
      corn flour per kilogram BM) at 70 to 90 min before racing. RESULTS: At 25 min
      before performance, NaHCO3 had increased blood pH (7.48 +/- 0.02 vs PL: 7.41 +/-
      0.03, P = .005) and bicarbonate concentrations (29.1 +/- 1.8 vs PL: 23.9 +/- 1.6
      mmol/L, P < .001), whereas BM, urine specific gravity, and plasma volume changes
      were similar between trials. Rowing ergometer times were similar between trials
      (NaHCO3: 397.8 +/- 12.6; PL: 398.6 +/- 13.8 s, P = .417), whereas posttest
      bicarbonate (11.6 +/- 2.3 vs 9.4 +/- 1.8 mmol/L, P = .003) and lactate
      concentration increases (13.4 +/- 1.7 vs 11.9 +/- 1.9 mmol/L, P = .001) were
      greater with NaHCO3. CONCLUSION: Sodium bicarbonate did not further enhance
      rehydration or performance in lightweight rowers when undertaking recommended
      post-weigh-in nutritional recovery strategies.

PMID- 21941013
TI  - Hyponatremia in the 2009 161-km Western States Endurance Run.
AB  - PURPOSE: To determine the incidence of exercise-associated hyponatremia (EAH),
      the associated biochemical measurements and risk factors for EAH, and whether
      there is an association between postrace blood sodium concentration ([Na+]) and
      changes in body mass among participants in the 2009 Western States Endurance Run,
      a 161-km mountain trail run. METHODS: Change in body mass, postrace [Na+], and
      blood creatine phosphokinase (CPK) concentration, and selected runner
      characteristics were evaluated among consenting competitors. RESULTS: Of the 47
      study participants, 14 (30%) had EAH as defined by a postrace [Na+] <135 mmol/L.
      Postrace [Na+] and percent change in body mass were directly related (r = .30, P
      = .044), and 50% of those with EAH had body mass losses of 3-6%. EAH was
      unrelated to age, sex, finish time, or use of nonsteroidal anti-inflammatory
      drugs during the run, but those with EAH had completed a smaller (P = .03) number
      of 161-km ultramarathons. The relationship of CPK levels to postrace [Na+] did
      not reach statistical significance (r = -.25, P = .097). CONCLUSIONS: EAH was
      common (30%) among finishers of this 161-km ultramarathon and it was not unusual
      for those with EAH to be dehydrated. As such, changes in body mass should not be
      relied upon in the assessment for EAH during 161-km ultramarathons.

PMID- 21941016
TI  - Toe and earlobe capillary blood sampling for lactate threshold determination in
      rowing.
AB  - PURPOSE: In rowing ergometry, blood for determining lactate concentration can be
      removed from the toe tip without the rower having to stop. The purpose of the
      study was to examine whether sampling blood from the toe versus the earlobe would
      affect lactate threshold (Tlac) determination. METHODS: Ten physically active
      males (mean +/- age 21.2 +/- 2.3 y; stature 179.2 +/- 7.5 cm; body mass 81.7 +/-
      12.7 kg) completed a multistage, 3 min incremental protocol on the Concept II
      rowing ergometer. Blood was sampled simultaneously from the toe tip and earlobe
      between stages. Three different methods were used to determine Tlac. RESULTS:
      There were wider variations due to the method of Tlac determination than due to
      the sample site; for example, ANOVA results for power output were F(1.25, 11.25)
      = 11.385, P = .004 for method and F(1, 9) = 0.633, P = .45 for site. The greatest
      differences in Tlac due to sample site in rowing occurred when Tlac was
      determined using an increase in blood lactate concentration by >1 mmol/L from
      baseline (TlacDelta1). CONCLUSIONS: The toe tip can be used as a suitable sample
      site for blood collection during rowing ergometry, but caution is needed when
      using the earlobe and toe tip interchangeably to prescribe training intensities
      based on Tlac, especially when using TlacDelta1 or at lower concentrations of
      lactate.

PMID- 21941017
TI  - Effect of daily cold water immersion on heart rate variability and subjective
      ratings of well-being in highly trained swimmers.
AB  - PURPOSE: We investigated the effect of daily cold water immersion (CWI), during a
      typical training week, on parasympathetic activity and subjective ratings of well
      being. METHODS: Over two different weeks, eight highly trained swimmers (4 men;
      19.6 +/- 3.2 y) performed their usual training load (5 d/wk, approx. 21 h/wk).
      Last training session of each training day was immediately followed by 5 min of
      seated recovery, in randomized order, with CWI (15 degrees C) or without (CON).
      Each morning before the first training session (6:30 AM) during the two
      experimental weeks, subjective ratings of well-being (eg, quality of sleep) were
      assessed and the R-R intervals were recorded for 5 min in supine position. A
      vagal-related index (ie, natural logarithm of the square root of the mean of the
      sum of the squares of differences between adjacent normal R-R intervals; Ln
      rMSSD) was calculated from the last 3-min segment. RESULTS: Compared with CON,
      CWI effect on Ln rMSSD was rated as possibly beneficial on day 2 [7.0% (-3; 19)],
      likely beneficial on day 3 [20.0% (1.5; 43.5)], very likely beneficial on day 4
      [30.4% (12.2; 51.6)] and likely beneficial on day 5 [24.1% (-0.4; 54.8)]. Cold
      water immersion was associated with a likely greater quality of sleep on day 2
      [30.0% (2.7; 64.6)], very likely on day 3 [31.0% (5.0; 63.1)] and likely on day 4
      [38.6% (11.4; 72.4)] when compared with CON. CONCLUSION: Five minutes of CWI
      following training can reduce the usual exercise-induced decrease in
      parasympathetic activity and is associated with improved rating of perceived
      sleep quality.

PMID- 21941018
TI  - Physical activity levels of adolescent girls during dance classes.
AB  - BACKGROUND: The aims of this study were to describe the physical activity levels
      of girls during dance classes and to identify factors associated with moderate-to
      vigorous physical activity (MVPA) in those classes. METHODS: Participants were
      137 girls (11 to 18 years-old) enrolled in ballet, jazz, or tap dance classes
      from 11 dance studios. Participants wore an accelerometer during the selected
      dance class on 2 separate days. Factors hypothesized to be associated with MVPA
      were dance style, instructional level, instructor's experience, percent of class
      time spent in choreography, and participants' age, race/ethnicity, BMI-for-age
      percentile, and years of dance training. Data were analyzed using generalized
      linear mixed models. RESULTS: Girls engaged in 9.8 minutes of MVPA, 6.0 minutes
      of moderate, 3.8 minutes of vigorous, 39.3 minutes of light, and 10.9 minutes of
      sedentary behavior per hour of dance class participation. Jazz/tap classes
      provided more MVPA than ballet classes, and intermediate level classes provided
      more MVPA than advanced level classes. Girls with more dance training obtained
      more MVPA than girls with less dance training. CONCLUSION: Dance classes provide
      valuable opportunities for adolescent girls to be physically active.

PMID- 21941020
TI  - Motor-unit pool model of continuous and discrete force variability.
AB  - The purpose of this study was to investigate the mechanisms contributing to the
      different scaling functions between force and force variability in continuous and
      discrete isometric forces. Muscle forces were simulated with the Fuglevand et al.
      (1993) model of motor unit recruitment and rate coding, and a range of
      recruitment and firing properties were manipulated. The influence of time-to-peak
      force on the discrete force variability was also examined. The results revealed
      that the peak firing rate, the synchrony between motoneurons, and the recruitment
      range contributed to the different variability functions in continuous and
      discrete forces. The shorter time-to-peak force led to higher variability in the
      peak force. The findings show that the model can produce the distinct properties
      of the force variability scaling functions in continuous and discrete forces. The
      simulation results provide preliminary insight into the neuromuscular mechanisms
      of the different force variability functions in continuous and discrete isometric
      forces.

PMID- 21941021
TI  - Effects of medio-lateral postural perturbation induced by voluntary arm raising
      on the biomechanical organization of rapid step initiation.
AB  - This study examined how the central nervous system organizes mediolateral (ML)
      "anticipatory postural adjustments" (APAs) for stepping initiation (SI) to take
      into account the postural perturbation induced by voluntary lateral arm raising.
      Subjects purposely stepped in isolation ("isolated stepping") or in combination
      with lateral raising of dominant arm ("motor sequence"). SI was carried out with
      the leg ipsilateral or controlateral to raising arm. Results showed that APA
      amplitude increased from "ipsilateral isolated stepping" to "ipsilateral
      sequence", but did not change in conditions involving controlateral leg; ML
      instability increased from "ipsilateral isolated stepping" to "ipsilateral
      sequence", but decreased from "controlateral isolated stepping" to "controlateral
      sequence". These changes were exacerbated when inertia was added at the hand
      during raising. These results suggest that APAs for SI are globally scaled as a
      function of the biomechanical consequences of forthcoming arm movement on ML
      postural stability.

PMID- 21941022
TI  - Facilitation of non-preferred coordination patterns during the transition from
      discrete to continuous movements.
AB  - This study investigates how motor coordination undergoes the passage from a
      discrete to a continuous movement regime. Participants repeated concatenated
      discrete movements with each hand such that one hand was lagging the other by a
      quarter of a cycle (i.e., with a 90 degrees  phase difference). As movement
      frequency increased, the tendency to persist in this relative phase competed with
      a progressive effect of the interlimb coupling favoring 0 degrees  and 180
      degrees . In 61% of the participants, a switch from a discrete to a continuous
      motion regime was accompanied by a shift toward the 0 degrees  or 180 degrees .
      The 0 degrees  was more often favored than 180 degrees . The remaining
      participants sustained a relative phase close to 90 degrees  even at the highest
      movement frequency and proved to be more accurate at the initial lowest
      frequency. These findings indicate that a priming effect may circumvent the
      tendency to produce preferred patterns and favor the production of nonpreferred
      patterns and that initial individual differences affect how motor coordination
      evolves with changing constraints.

PMID- 21941023
TI  - Age-related changes in postural control: rambling and trembling trajectories.
AB  - This study identified and quantified rambling and trembling properties of the
      postural control system of children 4-12 years of age. Forty five children of
      varying ages (4-, 8-, and 12-years) and 15 adults stood upright on a force plate
      and performed 5 trials with and 5 trials without vision with each trial lasting
      30 s. Center of pressure, rambling, trembling, mean sway amplitude, and
      predominant frequency were obtained. Results revealed that the displacement of
      the center of pressure and overall rambling trajectories were age-related with
      younger children swaying more than older children and adults. Similarly, overall
      trembling trajectories for younger children were larger compared with older
      children and adults. These results suggested that a younger child's larger body
      sway mostly results from difficulties using sensory information when estimating
      overall body position and velocity in an upright stance and is less a result from
      the noise in the postural control system.

PMID- 21941026
TI  - Correlations between health status and OralChromaTM-determined volatile sulfide
      levels in mouth air of the elderly.
AB  - Dimethyl sulfide (DMS), a volatile sulfur compound (VSC) found in mouth air, is
      thought to be associated with systemic diseases; this in contrast to the two
      other VSCs found in mouth air: hydrogen sulfide and methyl mercaptan (MM). This
      study aimed to validate the relationship between DMS in mouth air and oral and
      systemic factors. The subjects were 393 elderly Japanese volunteers participating
      in an oral and systemic health survey. They were surveyed for the concentration
      of VSC components in their mouth air and for their oral and systemic health
      status. Using logistic regression models, the prevalence of DMS in mouth air
      above the organoleptic threshold level (OTL) was found to be significantly
      associated with high-density lipoprotein (HDL) cholesterol level, medical history
      of colon polyps and asthma, being female, and the presence of MM in mouth air
      above the OTL. Our data suggest that systemic factors, such as a high serum HDL
      cholesterol level and a medical history of asthma and colon polyps, might be more
      prominent in subjects with elevated DMS. The differences, although statistically
      significant, are quite small. They also indicate that an oral factor, such as a
      high MM mouth-air level also influences the DMS mouth-air level in addition to
      systemic factors.

PMID- 21941025
TI  - Myc enforces overexpression of EZH2 in early prostatic neoplasia via
      transcriptional and post-transcriptional mechanisms.
AB  - EZH2 is part of the PRC2 polycomb repressive complex that is overexpressed in
      multiple cancer types and has been implicated in prostate cancer initiation and
      progression. Here, we identify EZH2 as a target of the MYC oncogene in prostate
      cancer and show that MYC coordinately regulates EZH2 through transcriptional and
      post-transcriptional means.  Although prior studies in prostate cancer have
      revealed a number of possible mechanisms of EZH2 upregulation, these changes
      cannot account for the overexpression EZH2 in many primary prostate cancers, nor
      in most cases of high grade PIN.  We report that upregulation of Myc in the mouse
      prostate results in overexpression of EZH2 mRNA and protein which coincides with
      reductions in miR-26a and miR-26b, known regulators of EZH2 in some non-prostate
      cell types, albeit not in others.  Further, in human prostate cancer cells, Myc
      negatively regulates miR-26a and miR-26b via direct binding to their parental Pol
      II gene promoters, and forced overexpression of miR-26a and miR-26b in prostate
      cancer cells results in decreased EZH2 levels and suppressed proliferation. In
      human clinical samples, miR-26a and miR-26b are downregulated in most primary
      prostate cancers.  As a separate mechanism of EZH2 mRNA upregulation, we find
      that Myc binds directly to and activates the transcription of the EZH2 promoter.
      These results link two major pathways in prostate cancer by providing two
      additional and complementary Myc-regulated mechanisms by which EZH2 upregulation
      occurs and is enforced during prostatic carcinogenesis. Further, the results
      implicate EZH2-driven mechanisms by which Myc may stimulate prostate tumor
      initiation and disease progression.

PMID- 21941027
TI  - Evaluation of a new fiber-grating vision sensor for assessing pulmonary functions
      in healthy and COPD subjects.
AB  - Spirometry is practically the only tool to evaluate pulmonary functions. Other
      automatic systems comparable to spirometry are expected. A fiber-grating (FG)
      vision sensor is a non-contact respiratory monitoring system to detect changes in
      volumes by measuring the movement of laser spots on the body surface. We examined
      the contributions of the FG sensor to evaluating pulmonary functions. The FG
      sensor showed a linear correlation with spirometry in tidal volumes (TV) obtained
      from five controls (R = 0.98, P < 0.0001). We also showed agreement of TV between
      the two devices using Bland-Altman analysis. TV measured by the FG sensor were
      reproducible and applicable to distinct subjects. To detect airway obstruction,
      we performed forced expiration in controls (n = 16) and chronic obstructive
      pulmonary disease (COPD) patients (n = 18) with the FG sensor and spirometry.
      Forced expiratory volume in 1 s (FEV(1)) and FEV(1)/forced vital capacity in COPD
      patients were lower than those in controls by the FG sensor. In addition,
      prolonged expiration in natural breathing by the FG sensor was related to airflow
      limitation by spirometry. The FG sensor was helpful to measure volume changes and
      to evaluate pulmonary functions in controls and patients with COPD. Its upcoming
      clinical applications are promising for simplicity and feasibility.

PMID- 21941028
TI  - Mapping of low flip angles in magnetic resonance.
AB  - Errors in the flip angle have to be corrected in many magnetic resonance imaging
      applications, especially for T1 quantification. However, the existing methods of
      B1 mapping fail to measure lower values of the flip angle despite the fact that
      these are extensively used in dynamic acquisition and 3D imaging. In this study,
      the nonlinearity of the radiofrequency (RF) transmit chain, especially for very
      low flip angles, is investigated and a simple method is proposed to accurately
      determine both the gain of the RF transmitter and the B1 field map for low flip
      angles. The method makes use of the spoiled gradient echo sequence with long
      repetition time (TR), such as applied in the double-angle method. It uses an
      image acquired with a flip angle of 90 degrees  as a reference image that is
      robust to B1 inhomogeneity. The ratio of the image at flip angle alpha to the
      image at a flip angle of 90 degrees  enables us to calculate the actual value of
      alpha. This study was carried out at 1.5 and 4.7 T, showing that the linearity of
      the RF supply system is highly dependent on the hardware. The method proposed
      here allows us to measure the flip angle from 1 degrees  to 60 degrees  with a
      maximal uncertainty of 10% and to correct T1 maps based on the variable flip
      angle method.

PMID- 21941029
TI  - NEMA NU-04-based performance characteristics of the LabPET-8TM small animal PET
      scanner.
AB  - The objective of this study is to characterize the performance of the preclinical
      avalanche photodiode (APD)-based LabPET-8TM subsystem of the fully integrated
      trimodality PET/SPECT/CT TriumphTM scanner using the National Electrical
      Manufacturers Association (NEMA) NU 04-2008 protocol. The characterized
      performance parameters include the spatial resolution, sensitivity, scatter
      fraction, counts rate performance and image-quality characteristics. The PET
      system is fully digital using APD-based detector modules with highly integrated
      electronics. The detector assembly consists of phoswich pairs of
      Lu(1.9)Y(0.1)SiO(5) (LYSO) and Lu(0.4)Gd(1.6)SiO(5) (LGSO) crystals with
      dimensions of 2 * 2 * 14 mm(3) having 7.5 cm axial and 10 cm transverse field of
      view (FOV). The spatial resolution and sensitivity were measured using a small
      (22)Na point source at different positions in the scanner's FOV. The scatter
      fraction and count rate characteristics were measured using mouse- and rat-sized
      phantoms fitted with an (18)F line source. The overall imaging capabilities of
      the scanner were assessed using the NEMA image-quality phantom and laboratory
      animal studies. The NEMA-based radial and tangential spatial resolution ranged
      from 1.7 mm at the center of the FOV to 2.59 mm at a radial offset of 2.5 cm and
      from 1.85 mm at the center of the FOV to 1.76 mm at a radial offset of 2.5 cm,
      respectively. Iterative reconstruction improved the spatial resolution to 0.84 mm
      at the center of the FOV. The total absolute system sensitivity is 12.74% for an
      energy window of 250-650 keV. For the mouse-sized phantom, the peak noise
      equivalent count rate (NECR) is 183 kcps at 2.07 MBq cc(-1), whereas the peak
      true count rate is 320 kcps at 2.5 MBq cc(-1) with a scatter fraction of 19%. The
      rat-sized phantom had a scatter fraction of 31%, with a peak NECR of 67 kcps at
      0.23 MBq cc(-1) and a peak true count rate of 186 kcps at 0.27 MBq cc(-1). The
      average activity concentration and percentage standard deviation were 126.97 kBq
      ml(-1) and 7%, respectively. The performance of the LabPET-8TM scanner was
      characterized based on the NEMA NU 04-2008 standards. The all in all performance
      demonstrates that the LabPET-8TM system is able to produce high-quality and
      highly contrasted images in a reasonable time, and as such it is well suited for
      preclinical molecular imaging-based research.

PMID- 21941030
TI  - Experimental determination of the energy response of alanine pellets in the high
      dose rate 192Ir spectrum.
AB  - An experimental determination of the energy correction factor for
      alanine/paraffin pellets in the 192Ir spectrum at varying distances from the
      source is presented. Alanine dosimeters were irradiated in water under full
      scatter conditions with a high dose rate (HDR) 192Ir source (Flexisource), using
      a dedicated holder. Up to six line sources (catheters) fit in a regular pattern
      at fixed radial distances from the holder axis, the alanine detector being placed
      at the centre of the holder. The HDR source was stepping every 0.5 cm within a
      trocar needle within +/- 3.0 cm around the medial plane through the detector in
      order to achieve dose homogeneity within the detector volume. The energy
      correction factor of alanine/paraffin pellets in 192Ir relative to 60Co was
      experimentally determined as the inverse ratio of the dose to water measured in
      water around the 192Ir source to the dose to water calculated in water using the
      TG-43 formalism. The pellets were read out with a Bruker EMX(micro) spectrometer
      (X-band). The amplitude of the central line in the alanine absorption spectrum
      from pellets irradiated within the 192Ir spectrum was directly compared with the
      amplitude from 60Co-irradiated pellets. The energy correction factors of Harwell
      pellets irradiated in the 192Ir spectrum are 1.029 +/- 0.02, 1.027 +/- 0.02 and
      1.045 +/- 0.02 at a mean weighted source-detector distance of 2.0, 2.9 and 5.3
      cm, respectively. The experimentally obtained values for the energy response are
      1.3% lower compared to the theoretical values for radial distances smaller than 3
      cm.

PMID- 21941031
TI  - The effect of CT dose on glenohumeral joint congruency measurements using 3D
      reconstructed patient-specific bone models.
AB  - The study of joint congruency at the glenohumeral joint of the shoulder using
      computed tomography (CT) and three-dimensional (3D) reconstructions of joint
      surfaces is an area of significant clinical interest. However, ionizing radiation
      delivered to patients during CT examinations is much higher than other types of
      radiological imaging. The shoulder represents a significant challenge for this
      modality as it is adjacent to the thyroid gland and breast tissue. The objective
      of this study was to determine the optimal CT scanning techniques that would
      minimize radiation dose while accurately quantifying joint congruency of the
      shoulder. The results suggest that only one-tenth of the standard applied total
      current (mA) and a pitch ratio of 1.375:1 was necessary to produce joint
      congruency values consistent with that of the higher dose scans. Using the CT
      scanning techniques examined in this study, the effective dose applied to the
      shoulder to quantify joint congruency was reduced by 88.9% compared to standard
      clinical CT imaging techniques.

PMID- 21941032
TI  - Fabrication of discrete gallium nanoislands on the surface of a Si(001) substrate
      using a focused ion beam.
AB  - A gallium focused ion beam (FIB) has been used to implant Ga at specific sites on
      the surface of undoped Si(001) substrates. Upon annealing at 600  degrees C,
      discrete nanoscale surface islands form within the FIB patterned regions when the
      total Ga ion dose, or fluence, is greater than 1.0 * 10(16) ions cm( - 2). The
      number of islands depends on the size of the irradiated region and a single
      island can be achieved for a FIB milled region that is 100 nm * 100 nm. The
      average sizes of the islands were found to range from 24.5 nm when exposed to a
      total ion dose of 1.2 * 10(16) ions cm( - 2) to 45 nm for a dose of 3.0 * 10(16)
      ions cm( - 2). We have confirmed that these surface islands are metallic Ga by
      performing a selective chemical etch that removes the islands and by transmission
      electron microscopy characterization. These patterned Ga surface templates could
      serve as nucleation sites for the lateral arrangement of discrete quantum dot
      structures.

PMID- 21941033
TI  - Active doping of B in silicon nanostructures and development of a Si quantum dot
      solar cell.
AB  - Active doping of B was observed in nanometer silicon layers confined in SiO(2)
      layers by secondary ion mass spectrometry (SIMS) depth profiling analysis and
      confirmed by Hall effect measurements. The uniformly distributed boron atoms in
      the B-doped silicon layers of [SiO(2) (8 nm)/B-doped Si(10 nm)](5) films turned
      out to be segregated into the Si/SiO(2) interfaces and the Si bulk, forming a
      distinct bimodal distribution by annealing at high temperature. B atoms in the Si
      layers were found to preferentially substitute inactive three-fold Si atoms in
      the grain boundaries and then substitute the four-fold Si atoms to achieve
      electrically active doping. As a result, active doping of B is initiated at high
      doping concentrations above 1.1 * 10(20) atoms cm( - 3) and high active doping of
      3 * 10(20) atoms cm( - 3) could be achieved. The active doping in ultra-thin Si
      layers was implemented for silicon quantum dots (QDs) to realize a Si QD solar
      cell. A high energy-conversion efficiency of 13.4% was realized from a p-type Si
      QD solar cell with B concentration of 4 * 10(20) atoms cm( - 3).

PMID- 21941034
TI  - Microstructure evolution and photoluminescence in nanocrystalline Mg(x)Zn(1 - x)O
      thin films.
AB  - The effects of Mg concentration and annealing temperature on the characteristics
      of nanocrystalline Mg(x)Zn(1 - x)O thin films (where x = 0-0.4) were studied
      using electron microscopy and photoluminescence. The films were prepared by a sol
      gel method. The solid solubility limit of MgO in ZnO for the sol-gel-derived
      Mg(x)Zn(1 - x)O films in the present study was determined to be ~ 20 at.%.
      Microstructural characterization of the films showed that the wurtzite
      crystallites decrease in size with increase in Mg concentration up to the
      solubility limit. Increasing Mg concentration beyond the solubility limit
      resulted in a decrease in crystallinity of the films. The bandgap energy was
      found to increase with Mg concentration whereas the linewidth first increased and
      then decreased when the Mg concentration was increased beyond the solubility
      limit. Photoluminescence properties have been correlated to the microstructure of
      the films. A growth mechanism for Mg(x)Zn(1 - x)O nanocrystalline films under the
      present processing conditions has also been proposed.

PMID- 21941035
TI  - A porous silicon optical microcavity for sensitive bacteria detection.
AB  - A porous silicon microcavity (PSM) is highly sensitive to subtle interface
      changes due to its high surface area, capillary condensation ability and a narrow
      resonance peak (~10 nm). Based on the well-defined optical properties of a PSM,
      we successfully fabricated a bacteria detection chip for molecular or subcellular
      analysis by surface modification using undecylenic acid (UA), and the specific
      recognition binding of vancomycin to the D-alanyl-D-alanine of bacteria. The red
      shift of the PSM resonance peak showed a good linear relationship with bacteria
      concentration ranging from 100 to 1000 bacteria ml( - 1) at the level of relative
      standard deviation of 0.994 and detection limit of 20 bacteria ml( - 1). The
      resulting PSM sensors demonstrated high sensitivity, good reproducibility, fast
      response and low cost for biosensing.

PMID- 21941036
TI  - Synthesis of tetrahedral quasi-type-II CdSe-CdS core-shell quantum dots.
AB  - Synthesis of colloidal nanocrystals of II-VI semiconductor materials has been
      refined in recent decades and their size dependent optoelectronic properties have
      been well established. Here we report a facile synthesis of CdSe-CdS core-shell
      heterostructures using a two-step hot injection process. Red-shifts in absorption
      and photoluminescence spectra show that the obtained quantum dots have quasi-type
      II alignment of energy levels. The obtained nanocrystals have a heterostructure
      with a large and highly faceted tetrahedral CdS shell grown epitaxially over a
      spherical CdSe core. The obtained morphology as well as high resolution electron
      microscopy confirms that the tetrahedral shell have a zinc blende crystal
      structure. A phenomenological mechanism for the growth and morphology of the
      nanocrystals is discussed.

PMID- 21941037
TI  - Spiral growth and formation of stacking faults and vacancy islands during
      molecular beam epitaxy of InN on GaN(0001).
AB  - The surface morphology and atomic structure of InN grown on the Ga-rich GaN(0001)
      pseudo (1 * 1) structure is studied by scanning tunneling microscopy. Spirals are
      formed as a result of screw dislocations emerging at the surface to relieve the
      strain from the lattice mismatch. Two additional types of strain relaxation
      mechanisms are also found, both due to the incorporation of excess Ga atoms from
      the starting pseudo (1 * 1) surface into the growing films. For films below 8 nm
      where the Ga concentration is larger than 7%, the formation of stacking faults at
      the InN/GaN interface produces a triangular network on the surface. The density
      of the stacking faults is found to decrease with film thickness and with the
      gradual consumption of the Ga atoms, and the network is therefore no longer
      observable above a critical thickness that varies from 8 to 10 nm. Instead,
      vacancy islands, one atomic layer deep, are formed to relieve the stain near the
      surface region. These results provide atomic scale insights into the interplay
      between the surface morphology and strain relaxation during the epitaxial growth
      of highly lattice mismatched InN/GaN heterostructures.

PMID- 21941038
TI  - Did the NFL Lockout expose the Achilles heel of competitive sports?

PMID- 21941039
TI  - Make dementia a public health priority in India.

PMID- 21941040
TI  - An assessment of rural health care delivery system in some areas of West Bengal
      an overview.
AB  - A cross sectional observational study was carried out in three districts of West
      Bengal by following observational, quantitative and qualitative methods during
      July to December 2006 to find out the extent of utilization, strengths,
      weaknesses and gap as well as suggest recommendations in connection with health
      care delivery system for the state of West Bengal, India. A total of 672 episodes
      of illnesses were reported (2 weeks recall) by the study population of the three
      selected districts in three geographically separated divisions of West Bengal.
      None did seek care from any health facilities for treatment in case of 221
      (32.89%) episodes; especially from tribal areas where in case of 76.19% none
      sought any health care from any facilities depended on their home remedies. In
      rest of episodes the (451), majority preferred government health facilities
      (38.58%), followed by Unqualified quacks (29.27%) due to low cost as well as
      living in close proximity, 27.27% preferred qualified Private practitioners and
      only 4.88% preferred AYUSH, as a first choice. Referral was mostly by self or by
      close relatives/families (61%) and not by a doctor. Awareness is required to
      avoid unnecessary referral. Cleanliness of the premises, face-lift, and clean
      toilet with privacy and availability of safe drinking water facilities could have
      an improved client satisfaction in rural health care delivery systems. This could
      be achieved through community participation with the involvement of PRI. However,
      as observed in the study RCH services including Family Planning as well as
      immunization services (preventive services) were utilized much better while there
      was a strong need of improvement of Post Natal Care, otherwise, Neonatal and
      Maternal mortality and morbidity will continue to be high.

PMID- 21941041
TI  - Eradicating and eliminating infectious diseases: past, present and future.
AB  - During the past 60 years, a number of infectious diseases have been targeted for
      eradication or elimination, with mixed results. While smallpox is the only one
      successfully eradicated so far, campaigns on yaws and malaria brought about a
      dramatic reduction in the incidence in the beginning of the campaign but
      ultimately could not achieve the desired goal. There is again a renewed interest
      in disease eradication. The World Health assembly in May 2010 passed a resolution
      calling for eradication of measles by 2015; the target of polio eradication still
      remains elusive. In view of these developments, it is appropriate time to revisit
      the concept of disease eradication and elimination, the achievements and failures
      of past eradication programmes and reasons thereof, and possibly apply these
      lessons while planning for the future activities. This paper based on the Dr.
      A.L.Saha Memorial Oration describes various infectious diseases that have been
      targeted for eradication or elimination since 1950s, the potential direct and
      indirect benefits from disease eradication, and the issues and opportunities for
      the future.

PMID- 21941042
TI  - Public health in India: issues and challenges.
AB  - Health is determined not only by medical care but also by determinants outside
      the medical sector. Public health approach is to deal with all these determinants
      of health which requires multi sectoral collaboration and inter-disciplinary
      coordination. Although there have been major improvements in public health since
      1950s, India is passing through demographic and environmental transition which is
      adding to burden of diseases. There is triple burden of diseases, viz.
      communicable, non-communicable and emerging infectious diseases. This high burden
      of disease, disability and death can only be addressed through an effective
      public health system. However, the growth of public health in India has been very
      slow due to low public expenditure on health, very few public health institutes
      in India and inadequate national standards for public health education. Recent
      years have seen efforts towards strengthening public health in India in the form
      of launch of NRHM, upgradation of health care infrastructure as per IPHS,
      initiation of more public health courses in some medical colleges and public
      health institutions and strengthening of public health functional capacity of
      states and districts under IDSP.

PMID- 21941043
TI  - Emergence of Schoengastiella ligula as the vector of scrub typhus outbreak in
      Darjeeling: has Leptotrombidium deliense been replaced?
AB  - BACKGROUND: Following a suspected outbreak of scrub typhus in Kurseong,
      Darjeeling, the Armed Forces Medical College, Pune was requested by the National
      Institute of Epidemiology and the State authorities to undertake investigation of
      the ongoing scrub typhus outbreak and suggest containment measures. MATERIALS AND
      METHODS: The epidemic team undertook clinical, entomological and serological
      studies to understand the local disease pattern and delineate high risk areas,
      host diversity by rodent trapping using Sherman traps, mite fauna diversity,
      abundance and vector species identification by phase contrast microscopy for
      preparation of electronic database and rodent and human serological studies by
      Weil Felix and PCR. RESULTS: The results indicate no association of scrub typhus
      with age and sex (P=0.37 and 0.74 respectively). The maximum cases occurred
      amongst the tea garden workers (73%) in the age group of 25-44 years. The
      predominant clinical presentation was fever (100%) with headache (75%),
      lymphadenopathy (45%) and presence of eschar (76.7%). The dominant host species
      (50% of trapped rodents) was shrew Suncus murinus, the index animal for scrub
      typhus, which contributed maximally to the vector abundance (52.96%) with a
      chigger index of 61.56. The trombiculid mite Schoengastiella ligula was the
      vector species much against the expected mite vector Leptotrombidium deliense, in
      the area. The study found the presence and abundance of vector species which
      corroborated well with the occurrence of cases in the various localities within
      the subdivisions. CONCLUSION: The study thus establishes Schoengastiella ligula
      as the vector of scrub typhus outbreak in Kurseong, Darjeeling. Preventive and
      containment measures with emphasis on reduction of man - vector contact were
      suggested to the state authorities to contain the outbreak.

PMID- 21941044
TI  - Public health engineering education in India: current scenario, opportunities and
      challenges.
AB  - Public health engineering can play an important and significant role in solving
      environmental health issues. In order to confront public health challenges
      emerging out of environmental problems we need adequately trained public health
      engineers / environmental engineers. Considering the current burden of disease
      attributable to environmental factors and expansion in scope of applications of
      public health / environmental engineering science, it is essential to understand
      the present scenario of teaching, training and capacity building programs in
      these areas. Against this background the present research was carried out to know
      the current teaching and training programs in public health engineering and
      related disciplines in India and to understand the potential opportunities and
      challenges available. A systematic, predefined approach was used to collect and
      assemble the data related to various teaching and training programs in public
      health engineering / environmental engineering in India. Public health
      engineering / environmental engineering education and training in the country is
      mainly offered through engineering institutions, as pre-service and in-service
      training. Pre-service programs include diploma, degree (graduate) and post
      graduate courses affiliated to various state technical boards, institutes and
      universities, whereas in-service training is mainly provided by Government of
      India recognized engineering and public health training institutes. Though
      trainees of these programs acquire skills related to engineering sciences, they
      significantly lack in public health skills. The teaching and training of public
      health engineering / environmental engineering is limited as a part of public
      health programs (MD Community Medicine, MPH, DPH) in India. There is need for
      developing teaching and training of public health engineering or environmental
      engineering as an interdisciplinary subject. Public health institutes can play an
      important and significant role in this regard by engaging themselves in
      initiating specialized programs in this domain.

PMID- 21941045
TI  - The allure of the private practitioner: is this the only alternative for the
      urban poor in India?
AB  - The main objective of the study has been to identify trajectories of health
      seeking behaviour of the urban poor, particularly their use of the private health
      sector, with the aim to identify strategies to improve quality of health care for
      this burgeoning population. This article presents findings from a slum settlement
      in Delhi where ethnographic sub-studies were carried out over two years among
      private health providers and selected households alongside a survey of household
      expenditure patterns. The primary research tools were in-depth interviews with
      practitioners and key informants as well as observations of clinical
      interactions. Illness narratives and case studies were documented over two years.
      The software package q.s.r. Nvivo was used for coding and content analysis. It
      was found that almost 90% of the respondents exclusively depend on local
      unlicensed and unregistered practitioners for basic primary health care. Long
      distances, time-consuming procedures, rude behaviour and, in many cases, bribes
      that had to be paid to staff in the hospitals were cited as major deterrents to
      utilising government facilities. Despite the public health consequences of
      inappropriate treatment protocols and misuse of drugs by these untrained private
      providers, in the absence of a structured urban primary health care system in the
      country, they seem to be the only alternative for the burgeoning urban poor in
      vast metros such as Delhi.

PMID- 21941046
TI  - Additional cash incentive within a conditional cash transfer scheme: a
      'controlled before and during' design evaluation study from India.
AB  - BACKGROUND: Conditional Cash Transfer (CCT) schemes have shown largely favorable
      changes in the health seeking behavior. This evaluation study assesses the
      process and performance of an Additional Cash Incentive (ACI) scheme within an
      ongoing CCT scheme in India, and document lessons. MATERIAL AND METHODS: A
      controlled before and during design study was conducted in Madhya Pradesh state
      of India, from August 2007 to March 2008, with increased in institutional
      deliveries as a primary outcome. In depth interviews, focus group discussions and
      household surveys were done for data collection. RESULTS: Lack of awareness about
      ACI scheme amongst general population and beneficiaries, cumbersome cash
      disbursement procedure, intricate eligibility criteria, extensive paper work, and
      insufficient focus on community involvement were the major implementation
      challenges. There were anecdotal reports of political interference and possible
      scope for corruption. At the end of implementation period, overall rate of
      institutional deliveries had increased in both target and control populations;
      however, the differences were not statistically significant. No cause and effect
      association could be proven by this study. CONCLUSIONS: Poor planning and
      coordination, and lack of public awareness about the scheme resulted in low
      utilization. Thus, proper IEC and training, detailed implementation plan,
      orientation training for implementer, sufficient budgetary allocation, and
      community participation should be an integral part for successful implementation
      of any such scheme. The lesson learned this evaluation study may be useful in any
      developing country setting and may be utilized for planning and implementation of
      any ACI scheme in future.

PMID- 21941047
TI  - Blood pressure distribution and its relation to anthropometric measurements among
      school children in Aligarh.
AB  - A cross-sectional study among 701 school children (12-16 years) was conducted in
      Aligarh to find out the prevalence of hypertension and to correlate school going
      adolescent's blood pressure with age, sex, height and weight. The weight was
      taken by a standardized weighing machine while height was measured using a
      standard stediometer. Blood pressure measurements were taken by a mercury
      sphygmomanometer. The distribution of blood pressure by anthropometric
      characteristics were studied. Mean, standard deviation and correlation
      coefficient were used for statistical analysis. The overall prevalence of
      hypertension was found to be 9.4%. Blood pressure of both gender appear to have
      positive correlation with anthropometric characteristics. Study recommends that
      children must be screened regularly for blood pressure so that remedial measure
      can be initiated as early as possible.

PMID- 21941048
TI  - Unintentional injuries among children admitted in a tertiary care hospital in
      North Kerala.
AB  - World Health Organization global disease update (2004) points out injuries as the
      sixth leading cause of morbidity and mortality in childhood. A descriptive
      hospital based study was conducted to find out the common types of unintentional
      injuries among children admitted for management of unintentional injuries in
      Pediatric Surgery department and Intensive Care Unit of a tertiary care hospital
      of North Kerala and to find out the contributing risk factors. A total of 400
      children admitted during the study period of 6 months of 2009 constituted the
      study population. Mechanical injuries comprising of Road traffic accidents and
      accidental fall were the major cause of unintentional injuries (36%), followed by
      Poisoning (22.3%). A higher proportion of unintentional injuries were noted to
      occur among children of younger mothers, overactive child, children belonging to
      extended or joint families, child left alone or with friends, pre-school
      children, male child and from urban dwellings. The study highlights the need to
      identify the different types of unintentional injuries and the risk factors of
      childhood injuries which require hospitalisation. Identification of risk factors
      will help to formulate strategies aimed at risk reduction and prevention of
      childhood injuries.

PMID- 21941049
TI  - A study on sex ratio at birth in suburban slums of Mumbai.
AB  - A cross sectional study was conducted in four selected suburban slums of Mumbai
      to determine the sex ratio at birth and to assess the various factors related to
      it. Information were collected on the sex of new born babies and other socio
      demographic characteristics of selected couples, including number of births,
      history of spontaneous and induced abortions and the preferred sex of siblings.
      Data were collected from a total of 302 families using a pre-tested interview
      schedule. There were 698 births of which 351(50.3%) were males and 347 females.
      The sex ratio at birth was 988 females for 1000 males. There were 84 abortions of
      which 60(71.4%) were induced and 24 (28.6%) were spontaneous. The reason stated
      for induced abortions was related to sex of the child in 31(51.7%) of the cases
      and in 26(83.9%) of these, the abortions were induced to prevent the birth of a
      female child. There was a preference for male children in the study families.
      Gender bias and its implications are discussed.

PMID- 21941050
TI  - Prevalence of hearing impairement in the district of Lucknow, India.
AB  - A multi-cluster study (survey) was carried out by department of ENT KG Medical
      University, Lucknow from July 2003 to August 2004 in rural and urban population
      of Lucknow district to estimate prevalence and causes of hearing impairment in
      the community. Data included audiological profile and basic ear examination that
      was analysed through EARFORM software program of WHO. Overall hearing impairment
      was seen in 15.14% of rural as opposed to 5.9% of urban population. A higher
      prevalence of disabling hearing impairment (DHI) in elderly and deafness in 0-10
      years age group was seen. The prevalence of sensorineural deafness necessitating
      hearing aids was 20% in rural and 50% in urban areas respectively. The presence
      of DHI was seen in 1/2 urban subjects and 1/3rd of rural counterparts. The
      incidence of cerumen / debris was very common in both types of population and the
      need of surgery was much more amongst rural subjects indicating more advanced /
      dangerous ear disease.

PMID- 21941051
TI  - Delayed presentation of anorectal malformations: need of community awareness.

PMID- 21941052
TI  - Effect of oral sucrose on pain during DPT immunization in older infants.

PMID- 21941053
TI  - Resistance pattern in drug-resistant pulmonary tuberculosis.
AB  - BACKGROUND: Drug-resistant tuberculosis is an important issue for public health.
      There is a rise in the trend of drug-resistant tuberculosis, especially multi
      drug resistance (MDR), in different parts of world, India being one of the high
      burden countries. This study is undertaken to assess the various patterns of
      resistance among confirmed drug resistant pulmonary tubercular patients and to
      initiate second line anti tubercular treatment. AIMS AND OBJECTIVES: To assess
      various resistance patterns among confirmed drug resistant pulmonary tubercular
      patients and for the initiation of appropriate drug regimens in our setup. STUDY
      DESIGN: An observational prospective study. MATERIALS AND METHODS: This study was
      conducted at Rajiv Gandhi Institute of Chest Diseases, Bangalore between January
      2005 and November 2010. A total of 309 drug resistant tuberculosis cases were
      studied. Sputum culture and drug sensitivity were carried out at National
      Tuberculosis Institute. Drug sensitivity testing done for all first line drugs,
      except pyrazinamide, by using LJ media. RESULTS: In this study, out of 309
      patients, MDR pattern was observed in 224 (72%), of which 20 (6.47%) had
      resistance only to isoniazid (INH) and rifampicin (RMP), 58 (18.7%) had
      resistance to INH, RMP, and either of the other first line drugs streptomycinor
      ethambutol and 146 (47.25%) had resistance to all first line drugs. Poly drug
      resistance pattern was observed in 72 (23.3%) and Mono drug resistance in 13
      (4.2%). CONCLUSION: In the present study the most common pattern observed is MDR
      with predominant resistance to INH. There is a rise in the number of drug
      resistant tuberculosis cases, especially MDR. Hence close monitoring of drug
      resistant pattern is required to formulate designs of different regimens in the
      treatment of drug resistant tuberculosis; especially MDR-TB based on accredited
      laboratory reports, in a specialized center which is very much essential for the
      betterment of the patients and the community.

PMID- 21941054
TI  - Relationship of body fat with insulin resistance and cardiometabolic risk factors
      among normal glucose-tolerant subjects.
AB  - BACKGROUND: The amount of body fat, rather than the amount of excess weight,
      determines the health risks of obesity, type 2 diabetes mellitus, and
      cardiovascular disease. AIMS: To look at the association of body fat percentage
      with cardiometabolic risk factors in subjects with normal glucose tolerance
      (NGT). SETTINGS AND DESIGN: Cross-section study from the Chennai Urban Rural
      Epidemiology Study. MATERIALS AND METHODS: Body fat was measured by Beurer body
      fat analyzer. Metabolic syndrome (MS) was diagnosed based on modified ATPIII
      guidelines. STATISTICAL ANALYSIS: Student's t test or one-way ANOVA (with Tukey's
      HSD) was used to compare groups for continuous variables. RESULTS: Body mass
      index, waist circumference, systolic and diastolic blood pressure, HOMA IR, serum
      cholesterol, and LDL cholesterol increased significantly with increasing tertiles
      of body fat (P<0.001). There was a linear increase in the percentage of body fat
      with increase in number of components of MS (no metabolic abnormality: 25 +/- 11,
      one metabolic abnormality: 28 +/- 10, two metabolic abnormalities: 33 +/- 8, and
      three and more metabolic abnormalities: 35 +/- 7) (P<0.001). Regression models
      showed significant association of body fat with MS after adjusting for age,
      gender, insulin resistance, and glycated hemoglobin (Odds ratio: 1.04, 95%
      confidence interval: 1.04 - 1.08, P<0.001). In linear regression analysis, body
      fat showed a significant association with insulin resistance after adjusting for
      age, gender, and glycated hemoglobin (beta=0.030, P<0.001). CONCLUSIONS: A
      significant association exists between body fat, MS, and cardiometabolic risk
      factors even among subjects with NGT.

PMID- 21941055
TI  - Frequency and nature of adverse drug reactions in elderly in-patients of two
      Indian medical college hospitals.
AB  - BACKGROUND: Adverse drug reactions (ADRs) are a major public health problem in
      the elderly. Although the Indian elderly represent 12.8% of the entire global
      elderly population, data on prevalence and predictors of ADRs in elderly Indians
      is extremely limited. AIM: To determine the prevalence, severity, preventability,
      length of hospital stays, and risk factors for ADRs in hospitalized Indian
      elderly. SETTING: Medicine wards of two tertiary care teaching hospitals. DESIGN:
      Prospective study was conducted between July 2007 and December 2009. MATERIALS
      AND METHODS: In-patients of either sex and aged >= 60 years were included and
      monitored for ADRs throughout their hospital stay. Severity (Hartwig et al.
      scale), preventability (Shumock and Thornton criteria) and increased length of
      stay (considering underlying disease, ADR, and discussion with clinicians) were
      assessed. STATISTICAL ANALYSIS: Bivariate analysis and subsequently multivariate
      logistic regression were used to determine the risk factors for developing ADRs.
      RESULTS: Over the study period, among the 920 patients monitored, 296 patients
      (32.2%) experienced 419 ADRs. Among all ADRs, 48.4% (203) were preventable.
      Majority of ADRs [226 (53.9%)] were moderate in severity. Therapeutic classes of
      drugs frequently associated with ADRs were the drugs used in diabetes [76
      (18.1%)] and antibacterials for systemic use [54 (12.9%)]. ADRs increased the
      hospital stay in 5.9% (54) of patients. Female gender [Odds Ratio: 1.52, 95%
      Confidence Interval:1.04-2.22, P=0.03] was observed as the influential risk
      factor for ADRs. CONCLUSION: One third of hospitalized elderly experienced ADRs.
      Interventions focused at preventable ADRs should be developed and implemented to
      reduce their implications.

PMID- 21941056
TI  - Knowledge, attitude and practice of pediatric critical care nurses towards pain:
      survey in a developing country setting.
AB  - BACKGROUND: Nurses' knowledge, sensitivity and attitudes about pain in children
      and its management affect their response and therefore management of pediatric
      pain. Children in critical care units undergo more painful procedures than those
      in general wards. AIMS: To study the knowledge, attitude and practice of nursing
      personnel catering to critically ill children in a developing country. SETTINGS
      AND DESIGN: Prospective questionnaire-based survey. MATERIALS AND METHODS: The
      survey was carried out in a tertiary care teaching hospital on nursing personnel
      in three pediatric/neonatal intensive care units. The domains studied were: i.
      Training and experience, ii. Knowledge of pediatric pain, iii. Individual
      attitude towards pain in children, iv. Personal practice(s) for pain alleviation,
      v. Pain assessment, and vi. Non-pharmacological measures adopted. STATISTICAL
      ANALYSIS: Descriptive statistics and logistic regression. RESULTS: Of the 81
      nursing personnel working in the three critical care units, 56 (69.1%) responded
      to the questionnaire. Only one-third of them had received formal training in
      pediatric nursing. Fifty percent of the respondents felt that infants perceive
      less pain than adults. Training in pediatric nursing was a significant
      contributing factor in the domain of knowledge (P=0.03). Restraint and
      distraction were the common modalities employed to facilitate painful procedures.
      Scientific approaches like eutectic mixture of local anesthetic and the judicious
      use of sedatives were not adopted routinely. Observing a child's face and posture
      were widely used parameters to assess pain (83%). None of the three critical care
      areas used a scoring system to assess pain. CONCLUSIONS: There are several
      lacunae in the knowledge and practice of nurses in developing countries which
      need to be improved by training.

PMID- 21941057
TI  - Polymorphisms of the gamma crystallin A and B genes among Indian patients with
      pediatric cataract.
AB  - BACKGROUND: Previous familial studies have reported co-segregation of mutation in
      gamma crystallin A and B CRYGA and CRYGB genes with childhood cataract. AIM: We
      investigated association of nucleotide variations in these genes in subjects with
      and without pediatric cataract from India. SETTINGS AND DESIGN: The study
      included 195 pediatric subjects including healthy children with no ocular defects
      and pediatric cataract cases. MATERIALS AND METHODS: Subjects were genotyped by
      PCR-RFLP method for exonic and intronic genetic variations in CRYGA and CRYGB.
      STATISTICAL ANALYSIS: The association of these polymorphisms with cataract was
      estimated by two way contingency tables and the risk allele was also analyzed for
      their functional impact using in silico tools. Results : No significant
      difference was observed between cases and control subjects for the frequencies of
      SNPs G198A (Intron A), T196C (Exon 3) of CRYGA and G449T (Exon 2) of CRYGB gene. 
      47C allele of rs2289917 in CRYGB showed the strongest association with cataract
      (Odd Ratio-OR=3.34, 95% Confidence Interval-CI 95% =1.82-6.12, P=0.00007). In
      silico analyses revealed that this polymorphism lies in a phylogenetically
      conserved region and impacts binding of a transcription factor, viz. progesterone
      receptor (PR) to CRYGB promoter. CONCLUSION: rs2289917 risk allele showed a
      strong association with increased vulnerability for pediatric cataract. The
      findings suggest that this association may be a secondary phenomenon related to
      genetic variation playing critical role in lens development during perinatal
      and/or pediatric growth. Present exploratory study provides a basis for further
      defining the role of PR as a regulator of CRYG locus in lens
      formation/transparency.

PMID- 21941059
TI  - Unusual case of isolated biventricular non-compaction presenting with stroke.
AB  - Prominent ventricular trabeculations are seen in a fetal heart. Isolated
      ventricular non-compaction (IVNC) is a rare form of primary cardiomyopathy. It
      usually presents with heart failure, arrhythmias and very rarely with thrombo
      embolic manifestation. The left ventricle is involved in the majority of the
      cases. Echocardiography is the principal modality for the diagnosis of this
      condition. IVNC may be misdiagnosed as dilated or hypertrophic cardiomyopathy
      wherein the prognosis and management do differ significantly. We report a case of
      a 38-year-old male with IVNC involving both the ventricles, who presented very
      unusually as stroke resulting from a cardiogenic embolus.

PMID- 21941058
TI  - A study of drug-drug interactions in cancer patients of a south Indian tertiary
      care teaching hospital.
AB  - BACKGROUND: Drug interactions in oncology are of particular importance owing to
      the narrow therapeutic index and the inherent toxicity of anticancer agents.
      Interactions with other medications can cause small change in pharmacokinetics or
      pharmacodynamics of chemotherapeutic agents that could significantly alter their
      safety and efficacy. AIM: To identify and document the potential drug-drug
      interactions in prescriptions of patients receiving cancer chemotherapy. Settings
      and Design : A tertiary care teaching hospital based prospective study. MATERIALS
      AND METHODS: Patients admitted in the medical oncology wards with different types
      of malignancies and receiving cancer chemotherapy during the period of June 2009
      to November 2009 were included in the study. A detailed data collection was done
      in a specially designed proforma with ethical approval and consent of patients
      and their prescriptions were subjected to drug-drug interaction screening using
      Drug Interaction Fact Software Version-4 and standard references. Incidence of
      drug-drug interactions, their types, correlation between age, cancer type, number
      of drugs prescribed and incidence of drug interactions were analyzed. STATISTICAL
      ANALYSIS: Logistic regression analysis and Odds ratio were performed to identify
      the incidence of drug-drug interactions and their correlation with the factors
      above mentioned. RESULTS: A total of 75 patients (32 males and 43 females; median
      age 56 years, age range 23-74) were enrolled in the study and their prescriptions
      were screened. 213 interactions were identified of which, 21 were major, 121 were
      moderate and 71 were minor. There were 13 (6.1%) clinically significant
      interactions between anticancer drugs and 14 (6.5%) drug-drug interactions
      between anticancer drugs and other drugs prescribed for co-morbidities. There was
      a positive correlation between number of drugs prescribed and drug interactions
      (P=0.011; OR 0.903). CONCLUSION: Though there was not any life threatening
      interactions, the potential interactions were brought to the oncologist purview
      for ensuring patients safety and to avoid undesirable effects.

PMID- 21941060
TI  - A rare diagnosis of multiple hemorrhagic metastases in brain.
AB  - A 30-year-old female presented with an episode of generalized tonic-clonic
      convulsions. The imaging revealed multiple hemorrhagic lesions in the brain.
      There was no significant past history except for a cardiac surgery two years ago,
      for a benign atrial myxoma. The diagnosis of probable metastases was thought of
      and a thorough workup was planned, to determine the primary. Surprisingly, no
      primary lesion was detected, and therefore, as a histological diagnosis was
      required, she underwent navigation-guided excisional biopsy of one of the
      lesions. The histopathology proved that it was a myxomatous lesion. Thus, a rare
      diagnosis of atrial myxoma presenting as hemorrhagic metastases of the brain was
      formed. Atrial myxoma is a benign tumor of the heart. It can embolize distally
      and can present with known embolic/ischemic manifestations. However, presentation
      as hemorrhagic mass lesions, involving multiple areas of the brain, after many
      years of complete surgical excision, is quite rare and is rarely considered as a
      differential diagnosis. Hence, such a possibility should be kept in mind and
      careful primary cardiac intervention, with preventive measures to minimize the
      chances of distal embolization should be undertaken. As only few such cases have
      been reported worldwide, no treatment protocol has been devised at present, and a
      close follow-up of these patients is warranted.

PMID- 21941061
TI  - Severe intestinal pseudo-obstruction following withdrawal from over-the-counter
      steroid abuse.
AB  - Relative adrenal insufficiency (RAI) is commonly diagnosed in critically ill
      patients failing to maintain a pressor response and/or with electrolyte
      abnormalities. We report a case of a 59-year-old man who presented with
      diverticular bleeding and developed prolonged ileus postoperatively. After
      observing arthritic joints on examination, further questioning revealed long
      term, high-dose steroid use for analgesic effect. Failure to produce an effective
      cortisol response was due to adrenal suppression from continuous steroid use.
      Immediate improvement of his ileus was seen after steroid replacement. Unreported
      self-medication is a frequent problem encountered in developing countries. RAI
      can be easily missed and requires a high index of suspicion in any patient who
      fails to respond to conventional treatment or with long-term steroid use.

PMID- 21941062
TI  - Ginkgo biloba: an ancient tree with new arrhythmic side effects.

PMID- 21941063
TI  - An unusual oral mass.

PMID- 21941064
TI  - Face to face: misplaced intrauterine device and abdominal ectopic pregnancy.

PMID- 21941065
TI  - Uncommon manifestation of organophosphorus poisoning.

PMID- 21941066
TI  - Perennial impression of an emerging arbovirus on the epidemiology of rheumatic
      diseases in south India: insights from the COPCORD study.
AB  - Are rheumatic musculoskeletal diseases (RMSD) given their due recognition by the
      medical fraternity and policy makers in India today? Focus on lifestyle diseases
      has taken away the importance of morbidity caused by musculoskeletal pain, which
      is one of the commonest ailments in the community. Poor awareness in general
      regarding the upcoming field of rheumatology and lack of proper data regarding
      these diseases in the country are the primary causes for this debacle. The
      epidemiology of RMSD in the country is fast changing, especially in the wake of
      viral epidemics, which leave their mark for months and years together. This view
      point emphasizes the burden of RMSD by highlighting the findings of two Community
      Oriented Programme for the Control of Rheumatic Diseases studies conducted to
      study the prevalence of RMSD in rural communities in the southern state of
      Kerala, which inadvertently captured the burden of RMSD following Chikungunya
      viral epidemics in the regions. Both the studies have reported a high prevalence
      of RMSD following the epidemics. The value of including RMSD in a national
      programme to combat the morbidity caused and to improve the health related
      quality of life of patients has been stressed upon, in the background of altering
      epidemiology of these disorders in the country.

PMID- 21941067
TI  - Ectopic liver tissue in umbilical cord.

PMID- 21941068
TI  - A young adult with progressive limb shaking and slowness.

PMID- 21941069
TI  - A framework for healthcare quality improvement in India: the time is here and
      now!
AB  - Healthcare in India has been undergoing rapid changes in the last decade. As
      demand outpaces supply, quality improvement (QI) initiatives and tools can be
      beneficial to enhance safe, effective, efficient, equitable and timely care.
      Healthcare quality is the degree to which health services for individuals and
      populations increase the likelihood of desired health outcomes and are consistent
      with current professional knowledge. This article discusses the framework for QI
      and reviews the Plan-Do-Study-Act (PDSA), Lean and Six Sigma methodologies, and
      briefly discusses key patient safety and quality measurement concepts. The PDSA
      cycle assists in testing the ideas through small tests of change or "pilots". Six
      Sigma aims at reducing variations in processes, and the Lean methodology
      predominantly focuses on enhancing process efficiency and eliminating non-value
      added steps in the process. It is likely that such structured problem solving
      approaches will provide an objective and systematic method of enhancing quality
      in healthcare institutions across India. As increasing attention being is paid on
      enhancing the quality of life through the Quality Council of India and
      accreditation of hospitals in India through the International Organization for
      standardization and National Accreditation Board for hospitals and healthcare
      providers, a focus on QI by institutional leaders and healthcare providers is key
      to enhancing the safety and quality of healthcare in India. Central to this also
      will be leadership buy-in, identification of a core faculty or team that will be
      the initiators of change, a respect for the need for faculty training and
      education in QI, measurement of issues to identify key priorities to focus on,
      and enhanced information systems where resources permit the same.

PMID- 21941070
TI  - Status epilepticus: why, what, and how.
AB  - Status epilepticus (SE) is an important neurological emergency with high
      mortality and morbidity. The first official definition of SE was the product of
      10 th Marseilles colloquium held in 1962 which was accepted by International
      League Against Epilepsy in 1964. There are as many types of SE as of seizures. SE
      is supposed to result from failure of normal mechanisms that terminate an
      isolated seizure. In half of the cases, there is no history of epilepsy and SE is
      precipitated by some intercurrent infection. In children, it is often infection,
      whereas in adults, the major causes are stroke, hypoxia, metabolic derangements,
      and alcohol intoxication or drug withdrawal. The treatment of SE aims at
      termination of SE, prevention of seizure recurrence, management of precipitating
      causes, and the management of complications. The extent of investigations done
      should be based on the clinical picture and cost benefit analysis. The first line
      antiepileptic drugs (AED) for SE include benzodiazepines, phenytoin,
      phosphenytoin, and sodium valproate. Mortality of SE ranges between 7 and 39% and
      depends on underlying cause and response to AEDs.

PMID- 21941071
TI  - A giant mesocolic lipoma--presenting as an irreducible sliding inguinal hernia: a
      case report of a rare clinical presentation.

PMID- 21941072
TI  - Bloodletting--an Ayurvedic perspective.

PMID- 21941073
TI  - A fluke occurrence of paramount significance.

PMID- 21941074
TI  - Reporting of outcomes in drug promotional materials distributed by pharmaceutical
      companies.

PMID- 21941075
TI  - Nonalcoholic fatty liver disease in south India.

PMID- 21941076
TI  - Large cavernous hemangioma of the skull base associated with an angular artery
      aneurysm.

PMID- 21941077
TI  - A curious case of chylothorax.

PMID- 21941078
TI  - An uncommon catastrophe associated with methotrexate.

PMID- 21941079
TI  - Altered sensorium in scrub typhus.

PMID- 21941080
TI  - Postgraduate entrance test reforms.

PMID- 21941081
TI  - How honest is the h-index in measuring individual research output?

PMID- 21941082
TI  - Senescence-associated microRNAs linked to tumorigenesis.

PMID- 21941083
TI  - A novel role of hydrogen peroxide in Kaposi sarcoma-associated herpesvirus
      reactivation.
AB  - Reactivation of Kaposi sarcoma-associated herpesvirus (KSHV) from latency for
      lytic replication plays a pivotal role in the development of KS tumors. However,
      the physiological factors of KSHV reactivation in KS patients remain undefined.
      Two recent studies independently discovered that the reactive oxygen species
      (ROS) H(2)O(2) induces KSHV reactivation in latently infected cells, which can be
      inhibited by H(2)O(2)-specific antioxidants. H(2)O(2) not only directly induces
      KSHV reactivation but also is involved in spontaneous lytic replication as well
      as reactivation stimulated by TPA, hypoxia, and cytokines. Furthermore, in a
      xenograft-based primary effusion lymphoma (PEL) mouse model, in vivo KSHV
      reactivation is also H(2)O(2)-dependent and can be suppressed by antioxidants.
      Mechanistically, H(2)O(2) primarily activates the MAPK pathways to induce viral
      lytic gene expression and replication. This new finding defines a novel role of
      H(2)O(2) in KS tumorigenesis and highlights great potentials of using
      antioxidants and anti-inflammatory drugs for the prevention and treatment of KS
      tumors.

PMID- 21941084
TI  - Stuck in a balancing act: histone methyltransferase activity of KMT1A traps
      alveolar rhabdomyosarcomas in an undifferentiated state.

PMID- 21941085
TI  - Global mitotic phosphorylation of C2H2 zinc finger protein linker peptides.
AB  - Cessation of transcriptional activity is a hallmark of cell division. Many
      biochemical pathways have been shown and proposed over the past few decades to
      explain the silence of this phase. In particular, many individual transcription
      factors have been shown to be inactivated by phosphorylation. In this report, we
      show the simultaneous phosphorylation and mitotic redistribution of a whole class
      of modified transcription factors. C(2)H(2) zinc finger proteins (ZFPs) represent
      the largest group of gene expression regulators in the human genome. Despite
      their diversity, C(2)H(2) ZFPs display striking conservation of small linker
      peptides joining their adjacent zinc finger modules. These linkers are critical
      for DNA binding activity. It has been proposed that conserved phosphorylation of
      these linker peptides could be a common mechanism for the inactivation of the DNA
      binding activity of C(2)H(2) ZFPs, during mitosis. Using a novel antibody, raised
      against the phosphorylated form of the most conserved linker peptide sequence, we
      are able to visualize the massive and simultaneous mitotic phosphorylation of
      hundreds of these proteins. We show that this wave of phosphorylation is tightly
      synchronized, starting in mid-prophase right after DNA condensation and before
      the breakdown of the nuclear envelope. This global phosphorylation is completely
      reversed in telophase. In addition, the exclusion of the phospho-linker signal
      from condensed DNA clearly demonstrates a common mechanism for the mitotic
      inactivation of C(2)H(2) ZFPs.

PMID- 21941086
TI  - Pharmacological activation of p53 triggers anticancer innate immune response
      through induction of ULBP2.
AB  - Escape of tumor cells from cell-intrinsic barrier mediated by tumor suppressors
      and cell-extrinsic barrier mediated by the immune system is crucial for
      tumorigenesis. Growing evidence suggests that reactivation of tumor suppressor
      function or restoration of anticancer immunity is promising strategy for
      anticancer therapy due to their high potential to combat cancer. p53, a key tumor
      suppressor, represses tumorigenesis by eliciting growth arrest, apoptosis or
      senescence in cancer cells. Here, we unravel that, apart from these cell
      autonomous effects, p53 activates the innate immune response against cancer
      cells. Our results show that pharmacological reactivation of p53 can stimulate
      the expression of ULPB2, a ligand for NK cell activating receptor NKG2D in human
      tumor cells of different origin, which enhance the susceptibility of tumor cells
      to NK cell-mediated killing. The molecular mechanism controlling ULPB2 expression
      by p53 is neither ATM/ATR- nor caspase-dependent. Using several approaches, we
      identified p53 as a direct transcriptional regulator of ULBP2 and found a p53
      response element within ULBP2 gene, which confers the p53 regulation.
      Furthermore, we demonstrated that demethylation of p53-binding region within
      ULBP2 gene was required for p53-dependent induction of ULPB2, which can be
      achieved via repression of DNA methyltransferases (DNMTs) by p53. This molecular
      evidence for the direct control of immunosurveillance by p53 links tumor
      suppressor activation to innate immune stimuli and provides a possibility to
      integrate cell-extrinsic and -intrinsic defenses against tumorigenesis by
      pharmacological activation of p53, which may increase the probability to achieve
      a durable therapeutic success.

PMID- 21941087
TI  - FoxM1 knockdown sensitizes human cancer cells to proteasome inhibitor-induced
      apoptosis but not to autophagy.
AB  - Apoptosis has been widely accepted as the primary mechanism of drug-induced cell
      death. Recently, a second type of cell death pathway has been demonstrated:
      autophagy, also called programmed type II cell death. Autophagy is a highly
      regulated process, by which selected components of a cell are degraded. It
      primarily functions as a cell survival mechanism under stress. However,
      persistent stress can also promote extensive autophagy leading to cell death.
      Forkhead box M1 (FoxM1), an oncogenic transcription factor that is abundantly
      expressed in a wide range of human cancers. Here we evaluated the role of FoxM1
      in sensitivity of human cancer cells to proteasome inhibitor-induced apoptosis
      and autophagy. We found that FoxM1 knockdown sensitized the human cancer cells to
      apoptotic cell death induced by proteasome inhibitors, such as, MG132, bortezomib
      and thiostrepton, while it did not affect the levels of autophagy following
      treatment with these drugs.

PMID- 21941088
TI  - Cost-effectiveness analysis of pneumococcal polysaccharide vaccination from age
      60 in Sao Paulo State, Brazil.
AB  - Vaccination of adults aged 60 years and older against Streptococcus pneumonia is
      not recommended in Brazil. The 23-valent polysaccharide pneumococcal vaccine
      (PPV23) is only available for institutionalized persons or with underlying
      diseases despite the substantial medical and economic burden related to
      pneumococcal infections in adults over than 59 years. The study aimed at
      evaluating the cost effectiveness of implementing a large PPV program in this
      population.  This analysis was performed using a static decision tree model.
      Demographic and epidemiological data were obtained from Brazilian official
      sources and international literature. Economic data were obtained from a study
      performed in 2007 in a public and a private hospital located in Sao Paulo.
      Vaccination was assumed to protect for 5 years with 60% effectiveness against
      bacteremic pneumococcal pneumonia (BPP) and 21% effectiveness against non
      bacteremic pneumococcal pneumonia (NBPP). Deterministic and sensitivity analyses
      were performed.  The pneumococcal polysaccharide vaccination saved 5,218 life
      year gained (LYG). The vaccination program was found to be cost effective in the
      social security and public health care perspectives with a mean incremental cost
      effectiveness ratio of R$10,887 and R$8,281 per LYG respectively. Results were
      sensitive to the vaccine effectiveness against NBPP, the incidence and case
      fatality rate of NBPP. From a societal perspective, PPV23 program for adults 60
      and older was found to be cost-saving.  Pneumococcal polysaccharide vaccination
      is clinically and economically favored over the present vaccination strategy, in
      which persons aged over 59 years in Sao Paulo, have not been vaccinated.

PMID- 21941089
TI  - Comparison of four recombinant hepatitis B vaccines applied on an accelerated
      schedule in healthy adults.
AB  - A post-marketing, double blind, randomised, controlled clinical trial to assess
      the immunogenicity and safety profiles of four commercially available recombinant
      hepatitis B vaccines was performed. The vaccines included in this study were
      Heberbiovac-HB ((r))  (Heber Biotec S.A., Havana, Cuba), Euvax-B ((r)) (LG
      Chemical Ltd., Seoul, Korea), Hepavax-Gene ((r))   (Greencross Vaccine Corp.,
      Seoul, Korea), and Engerix-B ((r))  (GlaxoSmithKline Biologicals, Rixensart,
      Belgium). Vaccines were administered intramuscularly to healthy adults in three
      20mg doses at monthly intervals (0 - 1 -  2 months). Four hundred volunteers aged
      18 to 45 years (average age, 35 years) non-reactive for serological markers of
      hepatitis B virus infection were vaccinated. Volunteers were randomly assigned
      (ratio 1:1:1:1) to one of the four treatment groups. The antibody response (anti
      HBs) was assessed at days 60, 90 and 365 post-vaccination using a commercial kit.
      The four vaccines showed to be safe and highly immunogenic. Similar
      seroprotection rates (anti-HBs >=10 IU/L) about one month after application of
      the second and third dose were obtained for Engerix-B ((r)) , Hepavax-Gene ((r))
      , Euvax-B ((r)) , and Heberbiovac-HB ((r))  vaccines 96.7%, 96.6%, 100%, 100% and
      98.8%, 89.5%, 100%, 100%, respectively.. Heberbiovac-HB ((r))  vaccine achieved
      significantly higher geometric mean antibody titers (GMT) and rate of good and 
      hyper-responders at all time-points post-vaccination. The GMT on day 365 after
      full vaccination was significantly reduced in all groups compared to day 90,
      although Heberbiovac-HB ((r))  showed the highest anti-HBs GMT and good
      responders rate. The four vaccines were well tolerated and poorly reactogenic. No
      serious adverse events were observed. This study confirms an overall good immune
      response and rapid priming for the  four vaccines in the course of an accelerated
      schedule, with higher anti-HBs geometric mean concentrations and better responses
      for Heberbiovac-HB ((r)) . [WHO primary Registry Number: RPCEC00000075].

PMID- 21941092
TI  - Enhanced immune response and protective efficacy of a Treponema pallidum Tp92 DNA
      vaccine vectored by chitosan nanoparticles and adjuvanted with IL-2.
AB  - AIMS: In this study, the immune-modulatory and protective efficacy of using an
      interleukin-2 (IL-2) expression plasmid as a genetic adjuvant and chitosan (CS)
      nanoparticles as vectors to enhance a Tp92 DNA vaccine candidate were
      investigated in a Treponema pallidum (Tp) rabbit challenge model. RESULTS: CS
      vectoring of pTp92 or pIL-2 were both demonstrated to augment anti-Tp92 antibody
      levels induced by pTp92 DNA vaccines. Interestingly, the combination of CS
      vectored Tp92 and pIL-2 led to the greatest enhancements of anti-Tp92 antibodies
      and T-cell proliferation (p < 0.05). At week 10 after the first immunization, 15
      of the 18 rabbits in each group were challenged with Tp Nichols strain and
      monitored for skin lesions and ulcer lesions. Ratios of positive skin lesions and
      ratios of ulcer lesions in groups immunized with pTp92 were significantly lower
      than those of the empty vector or PBS groups (p < 0.05), demonstrating that pTp92
      immunization elicited significant protective efficacy against the Tp Nichols
      strain challenge. CS vectored and pIL-2 adjuvanted pTp92 immunized animals
      exhibited the lowest rates of positive skin and ulcer lesions. METHODS: Male New
      Zealand white rabbits were randomly assigned to groups (n = 18/group) and
      immunized intramuscularly with pTp92 based plasmid DNA constructs (100 MUg of
      DNA/rabbit/immunization). Two weeks before Tp challenge (Week 8), three rabbits
      from each group were used to determine cytokine measurements and fifteen rabbits
      from each group were used for Tp challenge studies. CONCLUSIONS: Intramuscular
      injection of pTp92 induced strong humoral and cellular immune responses and
      conferred protection from Tp challenge in rabbits. The use of CS as a pTp92
      vector or pIL-2 as an adjuvant achieved a superior level of protective efficacy
      against Tp challenge, however CS vectored, IL-2 adjuvanted pTp92 immunization
      conferred the highest level of protective efficacy.

PMID- 21941093
TI  - Binding activity and immunogenic characterization of recombinant C-terminal
      quarter and half of the heavy chain of botulinum neurotoxin serotype A.
AB  - In the present study, we explored and compared the binding activity and
      immunogenic characterization of the most effective part corresponding to C
      terminal quarter of heavy chain of botulinum neurotoxin serotype A (AHc-C) with C
      terminal half of heavy chain of botulinum neurotoxin serotype A (AHc). Firstly,
      the fully soluble AHc-C protein successfully expressed in Escherichia coli by co
      expression with thioredoxin (Trx) was shown to bind with ganglioside as the AHc,
      indicating that the recombinant AHc-C protein retains a functionally active
      conformation. Furthermore, a solid-phase assay showed that the anti-AHc-C sera
      effectively inhibited the binding of AHc or AHc-C to the ganglioside GT1b, the
      first step in BoNT/A intoxication of neurons, as good as the anti-AHc sera.
      Finally, although the recombinant AHc-C protein still induced a high serum
      antibody titers and afforded protection level as the mice challenged with active
      botulinum neurotoxin serotype A, the immunization with AHc protein induced
      stronger protective potency than the AHc-C protein. The data presented in the
      report shows that there are the same ganglioside binding activity and different
      immunogenic characterization between the C-terminal quarter and half of heavy
      chain of botulinum neurotoxin serotype A. Therefore, the recombinant AHc-C
      protein can not only be developed into a minimal subunit candidate vaccine for
      prophylaxis against botulinum neurotoxin serotype A but also be used as a
      promising tool in the search for binding inhibitors and chimeric vaccines.

PMID- 21941091
TI  - Immunogenicity and safety of ZOSTAVAX((r)) approaching expiry potency in
      individuals aged >=50 years.
AB  - BACKGROUND: Age is a major risk factor for herpes zoster (HZ) and its potential
      long-term complication post-herpetic neuralgia (PHN). Due to the significant
      burden of HZ and PHN on patients' quality of life, it is vital that effective and
      well-tolerated vaccines are available to prevent HZ in older adults.
      ZOSTAVAX((r)) vaccine was developed to prevent HZ and PHN in individuals >=50
      years (y) of age, and its clinical efficacy and safety have been demonstrated.
      AIMS AND METHODS: This phase 4, open-label, multicenter study was undertaken to
      assess the immunogenicity and safety of a single dose of ZOSTAVAX (refrigerator
      stable formulation) given within 6 mo of its expiry date in individuals >=50 y of
      age. The geometric mean fold rise (GMFR) from pre-vaccination to 4 weeks post
      vaccination in varicella zoster virus (VZV) antibody titers was calculated. An
      acceptable antibody response was defined as a lower 95% confidence interval (CI)
      of GMFR > 1.4. Solicited and unsolicited injection-site reactions and systemic
      adverse events were recorded. RESULTS: The GMFR in VZV antibody titers was 3.1
      (95% CI: 2.6, 3.8), satisfying the criterion for an acceptable VZV antibody
      response to ZOSTAVAX (minimum requirement: 1.4 GMFR). An acceptable rise in VZV
      antibody titers was observed in individuals of 50-59 y of age (GMFR 3.9; 95% CI:
      2.9, 5.1) and in those >=60 y of age (GMFR 2.5; 95% CI: 1.9, 3.2). ZOSTAVAX was
      well tolerated; no serious adverse events were reported. CONCLUSION: ZOSTAVAX
      elicits an acceptable immune response in immunocompetent individuals >=50 y of
      age when stored as directed and administered during the 6 mo prior to expiration.

PMID- 21941094
TI  - Determinants of influenza vaccination among the adult and older Italian
      population with chronic obstructive pulmonary disease: a secondary analysis of
      the multipurpose ISTAT survey on health and health care use.
AB  - We analyzed seasonal flu vaccination rates among the Italian population suffering
      from Chronic Obstructive Pulmonary Disease (COPD) in order to identify socio
      demographic and clinical determinants for vaccination.  We used data from the
      survey "Health and health care use in Italy", which interviewed 5,935 persons
      (age 15 - 102 years) suffering from COPD in the period 2004-2005. For each
      respondent, information on socioeconomic and health conditions, smoking status
      and patterns of health care utilization were retrieved. After bivariate analysis,
      we used two multilevel regression models to assess determinants of vaccination
      among the adult and the older Italian population.  Overall 30.5% of adults
      (N=670) and 74.8% (N=2,796) of older people reported being vaccinated against
      seasonal flu. After controlling for potential confounders, older age increases
      the odds of vaccine uptake. Single marital status among the older people, smoking
      and not having contact with GPs in both age groups, are factors associated with
      non vaccination. Higher-educated elderly are less likely to be vaccinated, while
      coverage is higher among the wealthier adults.  Vaccine coverage among adults
      with COPD in Italy remains low, especially among those with no comorbidities, and
      aged less than 44 years. It is only in older age that vaccination rates increase
      substantially. We found several risk factors for non vaccination, such as
      smoking, single marital status, and not having contacts with GPs, which should be
      considered in developing strategies to increase the coverage of influenza vaccine
      among people with COPD in Italy.

PMID- 21941090
TI  - Recent developments for Pseudomonas vaccines.
AB  - Infections with Pseudomonas aeruginosa are a major health problem for immune
      compromised patients and individuals with cystic fibrosis. A vaccine against: P.
      aeruginosa has long been sought after, but is so far not available. Several
      vaccine candidates have been assessed in experimental animals and humans, which
      include sub-cellular fractions, capsule components, purified and recombinant
      proteins. Unique characteristics of the host and the pathogen have complicated
      the vaccine development. This review summarizes the current state of vaccine
      development for this ubiquitous pathogen, in particular to provide mucosal
      immunity against infections of the respiratory tract in susceptible individuals
      with cystic fibrosis.

PMID- 21941095
TI  - Perceptions of malaria and vaccines in Kenya.
AB  - Malaria is a leading cause of morbidity and mortality in Kenya. To confront
      malaria, the Government of Kenya has been implementing and coordinating three
      approaches - vector control by distributing insecticide-treated bed nets and
      indoor residual spraying, case management, and the management of malaria during
      pregnancy. Immunization is recognized as one of the most cost-effective public
      health interventions. Efforts are underway to develop a malaria vaccine. The most
      advanced (RTS,S), is currently going through phase 3 trials. Although recent
      studies show the overwhelming support in the community for the introduction of a
      malaria vaccine, two issues - culture and the delivery of child immunization
      services - need to be considered.  Alongside the modern methods of malaria
      control described above, traditional methods coexist and act as barriers to
      attainment of universal immunization. The gender dimension of the immunization
      programme (where women are the main child caretakers) will also need to be
      addressed. There is an age dimension to child immunization programmes. Two age
      cohorts of parents, caregivers, or family members deserve particular attention.
      These are the youth who are about to initiate childbearing, and the elderly
      (particularly mother-in-laws who often play a role in child-rearing). Mothers who
      are less privileged and socially disadvantaged need particular attention when it
      comes to child immunization. Access to immunization services is often
      characterized in some Kenyan rural communities in terms of living near the main
      road, or in the remote inaccessible areas. Should a malaria vaccine become
      available in the future, a strategy to integrate it into the immunization
      programme in Kenya should take into account at least two issues. First, it must
      address the fact that alongside the formal approach in malaria control, there
      exist the informal traditional practices among communities. Secondly, it must
      address particular issues in the delivery of immunization services.

PMID- 21941096
TI  - Challenges and opportunities in the Israeli 2009 pandemic influenza vaccination
      program.
AB  - Vaccines are a cornerstone in any pandemic influenza preparedness plan.
      Successful supplementary mass vaccination programs require proper advance
      planning. We aimed to identify general, and Israeli specific, challenges and
      opportunities before initiating the Israeli pandemic influenza vaccination
      program in order to better plan implementation of the program. Following the
      vaccination campaign the analysis was retrospectively examined in order to
      determine whether the challenges were properly identified and whether the
      opportunities were indeed realized. The major challenges identified were
      prioritization; ongoing communication with the public; balancing between central
      management and accessibility; and preventing vaccination errors. The major
      opportunity was expected to be the chance to enhance cooperation and
      communication between different organizations both within and outside of the
      health system at local, national and international levels. The vaccination
      program was planned based on this analysis. In retrospect, the analysis
      identified the key challenges and opportunities and appropriate measures were
      taken. However, the criticalness of acceptance of the vaccine among health care
      practitioners was not given sufficient attention and should be addressed in
      future vaccination programs. Analysis of global and local challenges and
      opportunities served as a useful tool for planning a pandemic influenza
      vaccination program. Lessons learned from this analysis could serve to foster
      cooperation and communication between various agencies in the event of planning
      rapid mass vaccination programs as well as for more routine public health
      vaccination campaigns.

PMID- 21941097
TI  - 13-valent pneumococcal conjugate vaccine (PCV13).
AB  - The thirteen valent pneumococcal conjugate vaccine (PCV13, Prevenar 13(TM)) is
      the broader coverage successor to the highly effective seven valent vaccine
      (PCV7, Prevenar(TM)) which has reduced rates of pneumococcal disease in many
      countries. Despite the success of PCV7, pneumococcal disease due to non-PCV7
      serotypes remains a threat in many settings, in particular many developing
      countries with a high burden of pneumococcal disease where serotype 1 and 5 are
      among the most common serotypes. Disease due to certain non-PCV7 serotypes, in
      particular serotype 19A has also begun to increase in incidence in countries with
      widespread use of PCV7. PCV13 consists of thirteen pneumococcal capsular
      polysaccharides individually conjugated to the diphtheria-derived protein carrier
      CRM(197). In addition to serotypes 4, 6B, 9V, 14, 18C, 19F and 23F included in
      PCV7, PCV13 also includes serotypes 1, 3, 5, 6A, 7F and 19A. PCV13 was licensed
      on the basis of non-inferiority trials and has proved to be at least as safe and
      effective as PCV7. PCV13 replaced PCV7 in the childhood immunisation schedules of
      the USA and UK in 2010 and is being rolled out to an increasing number of
      developing countries during 2011. Here we review the current literature regarding
      this vaccine, describing safety, efficacy, global serotype coverage and use and
      future directions.

PMID- 21941098
TI  - Adverse events following immunization: easily preventable in developing
      countries.

PMID- 21941099
TI  - Active immunotherapeutics forum-Advance phase III active immunotherapy programs:
      just how well did the pre-clinical and early clinical trials translate? Case
      studies: with the benefit of hindsight, what are the three biggest lessons
      learned from pre-clinical and early clinical trials? Meeting report from
      Barcelona, May 12 2011.
AB  - The approval of Provenge (Dendreon) in 2010 signaled the dawn of a new era in the
      development of active immunotherapeutics. For cancer treatment, the approval of
      Provenge(r) demonstrates that the immune system can effectively be harnessed to
      combat cancer. The outlook for active immunotherapies looks bright in terms of
      promising new approaches and candidates, as well as novel adjuvants and treatment
      regimens for therapy development.

PMID- 21941105
TI  - How a disordered ubiquitin ligase maintains order in nuclear protein homeostasis.
AB  - Cells use protein quality control (PQC) systems to protect themselves from
      potentially harmful misfolded proteins. Many misfolded proteins are repaired by
      molecular chaperones, but irreparably damaged proteins must be destroyed.
      Eukaryotes predominantly destroy these abnormally folded proteins through the
      ubiquitin-proteasome pathway, which requires compartment-specific ubiquitin
      ligase complexes that mark substrates with ubiquitin for proteasome degradation.
      In the yeast nucleus, misfolded proteins are targeted for degradation by the
      ubiquitin ligase San1, which binds misfolded nuclear proteins directly and does
      not appear to require chaperones for substrate binding. San1 is also remarkably
      adaptable, as it is capable of ubiquitinating a structurally diverse assortment
      of abnormally folded substrates. We attribute this adaptability to San1's high
      degree of structural disorder, which provides flexibility and allows San1 to
      conform to differently shaped substrates. Here we review our recent work
      characterizing San1's distinctive mode of substrate recognition and the
      associated implications for PQC in the nucleus.

PMID- 21941106
TI  - Amphibian oocyte nuclei expressing lamin A with the progeria mutation E145K
      exhibit an increased elastic modulus.
AB  - Mutations in the human lamin A gene (LMNA) cause a wide range of diseases
      (laminopathies). Among these is the Hutchinson-Gilford progeria syndrome (HGPS),
      a rare premature aging disease. Most HGPS patients carry a silent point mutation,
      which activates a cryptic splice site resulting in the expression of a
      permanently isoprenylated and truncated lamin ADelta50/progerin. Another type of
      mutant lamin A namely, E145K-lamin A, also causes HGPS. E145K-lamin A induces
      profound changes in the nuclear architecture of patient cells as well as after
      expression in cultured cells. The E145K mutation is located in the alpha-helical
      central domain of lamin A, which is involved in lamin filament assembly. In vitro
      analyses of purified E145K-lamin A have revealed severe assembly defects into
      higher order lamin structures, which indicates an abnormal lateral association of
      protofilaments. To analyze how the altered assembly observed in vitro might
      influence the mechanics of a nuclear lamina formed by E145K-lamin A, mutant and
      wild type lamin A were ectopically expressed in amphibian oocytes. Both types
      form a lamina consisting of multi-layered sheets of filaments at the inner side
      of the nuclear envelope. The mechanical properties of isolated nuclei were
      measured by atomic force microscopy (AFM). From the resulting force curves, the
      stiffness of the lamina was estimated. The thickness of the resulting lamin A
      layer was then measured by TEM. The two parameters allowed us to estimate the
      elastic modulus (Young's modulus) of the lamina. Lamin A sheets made from E145K
      filaments have a higher Young's modulus compared to wild type filaments, i.e. the
      E145K-lamin A sheets are more rigid than wild type laminae of comparable
      thickness.

PMID- 21941107
TI  - Coordinating postmitotic nuclear pore complex assembly with abscission timing.
AB  - Cells divide and accurately inherit genomic and cellular content through
      synchronized changes in cellular organization and chromosome dynamics. Although
      DNA segregation, nuclear reformation, and cytokinesis/abscission temporally
      overlap, little is known about how these distinct events are coordinated to
      ensure accurate cell division. Recently, we found that disruption of postmitotic
      nuclear pore complex assembly, an essential aspect of the newly forming nuclear
      envelope, triggers an Aurora B-dependent delay in abscission. This delay is
      further characterized by mislocalized, aberrantly active Aurora B in the
      cytoplasm of midbody-stage cells. These results support a model in which an
      Aurora B-mediated abscission checkpoint provides surveillance of nuclear pore
      complex formation to ensure that elements of nuclear architecture are fully
      formed before daughter cells are physically separated. Here we discuss the
      process of nuclear pore complex assembly, describe potential mechanisms that may
      explain how this process could be coordinated with abscission, and postulate why
      such a checkpoint mechanism may exist.

PMID- 21941108
TI  - Composition, recruitment and regulation of the PRC2 complex.
AB  - The PRC2 histone methyltransferase complex is an important regulator of gene
      expression programs in metazoans. Gene expression regulation by the PRC2 complex
      is critical for development and cell differentiation. Several recent studies have
      begun to shed light on the molecular basis for the physiological function of the
      PRC2 complex. Here, we discuss some of these results and how they provide new
      insights into the composition, recruitment and regulation of the PRC2 complex.

PMID- 21941109
TI  - Proteasomes crossing the nuclear border.
AB  - Proteasomes localize to different compartments in eukaryotic cells, but the
      details of this dynamic distribution are poorly understood. Here, we discuss
      evidence linking proteasome activity to specific intranuclear locations and the
      potential mechanisms that may target these large proteolytic machines to the
      nucleus. Recent work has demonstrated the targeting of intact proteasome
      particles to newly formed nuclear compartments in a cell-free reconstitution
      assay. We discuss the difference between open and closed mitosis systems and the
      targeting of proteasomes to the nuclear periphery, as well as the nucleoplasm.
      Finally, we present a potential model for regulated assembly of the 26S
      proteasome holoenzyme inside the nucleus.

PMID- 21941110
TI  - Breach of the nuclear lamina during assembly of herpes simplex viruses.
AB  - Beneath the inner nuclear membrane lies the dense meshwork of the nuclear lamina,
      which provides structural support for the nuclear envelope and serves as an
      important organizing center for a number of nuclear and cytoplasmic constituents
      and processes. Herpesviruses have a significant and wide-ranging impact on human
      health, and their capacity to replicate and cause disease includes events that
      occur in the host cell nucleus. Herpesviruses begin assembly of progeny virus in
      the nuclei of infected cells and their capsids must escape the confines of the
      nucleus by budding through the inner nuclear membrane (INM) to proceed with later
      stages of virion assembly and egress. Access of viral capsids to the INM thus
      necessitates disruption of the dense nuclear lamina layer. We review herpesvirus
      effects on the nuclear lamina and in particular the roles of the herpes simplex
      virus-encoded nuclear envelope complex and viral kinases on lamin
      phosphorylation, dissociation, and nucleocapsid envelopment at the INM.

PMID- 21941112
TI  - Losing control: cancer's catastrophic transition.
AB  - Adaptability and "emergent" properties are the dominant characteristics of
      complex systems, whether naturally occurring or engineered. Structurally, a
      complex system might be made up of a large number of simpler components, or it
      might be formed from hierarchies of smaller numbers of interacting subsystems and
      work together to produce a defined function. The nucleus of a cell has all of
      these features, many of which may become disrupted in cancer and other disease
      states. The general view is that cancer progresses gradually over time; cells
      become premalignant, then increasingly abnormal before they become cancerous.
      However, recent work by Stephens et al. (2011) has revealed that cancer can
      emerge much more rapidly. Based on DNA sequences from multiple cancer samples of
      various types, they show that cancer can arise suddenly from a single
      catastrophic event that causes massive genomic rearrangement.

PMID- 21941111
TI  - Simian virus 40 induces lamin A/C fluctuations and nuclear envelope deformation
      during cell entry.
AB  - The canonical gate of viruses and viral genomes into the nucleus in non-dividing
      cells is the nuclear pore, embedded within the nuclear envelope. However, we
      found that for SV40, the nuclear envelope poses a major hurdle to infection: FISH
      analysis revealed that the majority of viral DNA remains trapped in the ER;
      silencing of Lamin A/C rendered the cells more susceptible to infection; and
      proliferating cells are more susceptible to infection than quiescent cells.
      Surprisingly, we observed that following SV40 infection the nuclear envelope,
      including lamins A/C, B1, B2 and the nuclear pore complex, was dramatically
      deformed, as seen by immunohistochemistry. The infection induced fluctuations in
      the level of lamin A/C, dephosphorylation of an unknown epitope and leakage to
      the cytoplasm just prior to and during nuclear entry. Deformations were
      transient, and the spherical structure of the nuclear envelope was restored
      subsequent to nuclear entry. Nuclear envelope deformations and lamin A/C
      dephosphorylation depended on caspase-6 cleavage of lamin A/C. Notably, we have
      previously reported that inhibition of caspase-6 abolishes SV40 infection. Taken
      together the results suggest that alterations of the nuclear lamina, induced by
      the infecting virus, are involved in the nuclear entry of the SV40 genome. We
      propose that SV40 utilize this unique, previously unknown mechanism for direct
      trafficking of its genome from the ER to the nucleus. As SV40 serves as a
      paradigm for the pathogenic human BK, JC and Merkel cell polyomavirus, this study
      suggests nuclear entry as a novel drug target for these infections.

PMID- 21941113
TI  - Variations in a team: major and minor variants of Arabidopsis thaliana rDNA
      genes.
AB  - While plant rRNA gene organization and expression have been studied for several
      decades, the repetitive nature and high sequence identity between the tandemly
      repeated units has prevented precise studies to determine which units are active
      and elucidate mechanisms of spatial and temporal transcriptional control. We have
      detected four variants among rRNA genes of Arabidopsis thaliana by analysis of
      the 3' external spacer region. Surprisingly, the most abundant variant,
      representing ~50% of the genes, is not expressed in wild-type plants but is
      transcribed in lines mutated in one of the two nucleolin genes. Analysis of
      Arabidopsis ecotypes indicated considerable variability in numbers and
      presence/absence of variants, although more closely-related ecotypes show similar
      profiles. Sequence analysis showed that one of the variants is not only
      unexpectedly located within a 5S RNA gene cluster in the pericentromeric region
      of chromosome 3 but is also potentially highly expressed in wild-type plants. We
      present a model to explain how transcription of this this unusual variant,
      maintained in an active state by nucleolin binding, could be involved in control
      of expression of the major variant, while absence of nucleolin leads to silencing
      of the minor variant and consequent expression of the major variant.

PMID- 21941116
TI  - International symposium on the physicochemical field for genetic activities.
      Awaji Island, Japan, January 24-26, 2011.
AB  - The beautiful resort island of Awaji, Japan was recently host to an international
      gathering of scientists interested in the physical, biochemical and biological
      aspects of components of the eukaryotic cell nucleus. The meeting featured
      speakers from many centers of research excellence in Japan as well as from around
      the world and was characterized by a unique focus on quantitative methods of
      analysis as applied to chromatin and chromosomes - termed "The Genofield". The
      meeting was organized by Professors Yasushi Hiraoka, Hitoshi Kurumizaka and
      Akatsuki Kimura.

PMID- 21941115
TI  - H3K9 histone acetylation predicts pluripotency and reprogramming capacity of ES
      cells.
AB  - The pluripotent genome is characterized by unique epigenetic features and a
      decondensed chromatin conformation. However, the relationship between epigenetic
      regulation and pluripotency is not altogether clear. Here, using an enhanced
      MEF/ESC fusion protocol, we compared the reprogramming potency and histone
      modifications of different embryonic stem cell (ESC) lines (R1, J1, E14, C57BL/6)
      and found that E14 ESCs are significantly less potent, with significantly reduced
      H3K9ac levels. Treatment of E14 ESCs with histone deacetylase (HDAC) inhibitors
      (HDACi) increased H3K9ac levels and restored their reprogramming capacity.
      Microarray and H3K9ac ChIP-seq analyses, suggested increased extracellular matrix
      (ECM) activity following HDACi treatment in E14 ESCs. These data suggest that
      H3K9ac may predict pluripotency and that increasing pluripotency by HDAC
      inhibition acts through H3K9ac to enhance the activity of target genes involved
      in ECM production to support pluripotency.

PMID- 21941117
TI  - The nucleolus: when 2 became 3.
AB  - Though the nucleolus is considered today as a multifunctional domain, its primary
      function is ribosome biogenesis. We have shown at the ultrastructural level that
      there are primarily two types of nucleolar organization: nucleoli containing
      three components in amniotes and two components in all other eukaryotes. In a
      recent report we made the additional, and surprising, finding that both types of
      nucleolar arrangement are found among living reptiles, viz. a bicompartmentalized
      nucleolus in turtles and a tricompartmentalized nucleolus in lizards, crocodiles
      and snakes. This latter organization occurs regardless of the species, the tissue
      or the developmental stages analyzed. These results are compatible with the view
      that the transition between bipartite and tripartite nucleoli coincided with the
      emergence of the amniotes within the Reptilia. They also support the previous
      hypothesis that turtles are primitive reptiles. The emergence in amniote
      vertebrates of a third nucleolar compartment might have imparted novel regulatory
      functions to the nucleolus, as well as perhaps, expanding the adaptability of
      ribosome synthesis to an ever changing environment, thus, enhancing the overall
      fitness of amniotic vertebrates.

PMID- 21941119
TI  - Heterochromatin maintenance and establishment: lessons from the mouse
      pericentromere.
AB  - Defined as a chromatin structure that remains condensed throughout the cell cycle
      heterochromatin is generally transcriptionally silent and is characterized by a
      specific molecular signature. Constitutive heterochromatin at the pericentromere
      is a conserved feature throughout evolution, which impacts genome stability.
      Here, we will summarize recent advances in our understanding of the dynamics of
      mouse pericentric heterochromatin during the cell cycle and development.
      Comparison with heterochromatin maintenance in fission yeast will enable
      discussions of the common basic principles and various mechanisms exploited in
      the distinct organisms.

PMID- 21941118
TI  - An inducible nuclear body in the Drosophila germinal vesicle.
AB  - When living egg chambers of Drosophila are isolated in a saline solution and
      gently squashed between a microscope slide and coverslip, prominent nuclear
      bodies (1 - 20 mm diameter) can be seen inside the oocyte nucleus or germinal
      vesicle (GV).  These bodies do not pre-exist within the GV and are not seen in
      material that is fixed in paraformaldehyde before squashing.  Instead, they form
      spontaneously within minutes after an egg chamber is damaged and the cytoplasm is
      exposed to the isolation medium.  Electron microscopy shows that the bodies lack
      an investing membrane and consist of closely packed, irregular particles 30-50 nm
      in diameter.  We used GFP-tagged proteins from the Carnegie Protein Trap Library
      to identify 22 proteins that are either enriched in the bodies or excluded from
      them.  We were unable to discern common features of proteins that are
      concentrated in the bodies, such as isoelectric point, molecular weight, or
      biological process.  Induced bodies are formed in GVs of flies that are null for
      coilin or WDR79, proteins that are required for formation of Cajal bodies (CBs). 
      We performed fluorescence recovery after photobleaching (FRAP) experiments on
      five GFP-tagged proteins that are enriched in the bodies.  Four of the proteins
      regained the full pre-bleach fluorescence intensity, indicating that the contents
      of the bodies are in dynamic equilibrium with the surrounding nucleoplasm. 
      Induced nuclear bodies presumably form as a result of unusual physico-chemical
      changes in the Drosophila GV.  We suggest that their behavior serves as a useful
      model for self-assembly of nuclear bodies in general, and we discuss the
      possibility that similar bodies may occur normally in cells of other organisms.

PMID- 21941120
TI  - A natural fast-cleaving branching ribozyme from the amoeboflagellate Naegleria
      pringsheimi.
AB  - The GIR1 branching ribozyme constitutes a separate class of naturally occurring
      ribozymes. Most studies have been performed with the single GIR1 known from the
      myxomycete Didymium iridis whereas the large number of GIR1s found in the
      amoeboflagellate Naegleria has remained largely uncharacterized. Here, we
      investigate ribozyme cleavage properties of a collection of Naegleria GIR1
      ribozymes and define the variant from N. pringsheimi as a suitable model due to
      its superior activity in vitro. We identify the minimal ribozyme by deletion
      analysis applying a new RNase R based assay for the branching reaction, and by
      mutational analysis we demonstrate a surprising effect on the activity of
      structural elements J2/10 and L9 located outside the core of the ribozyme. These
      elements are located in regions that differ mostly from the Didymium ribozyme and
      illustrate the usefulness of comparative ribozyme studies.

PMID- 21941121
TI  - sRNA-Xcc1, an integron-encoded transposon- and plasmid-transferred trans-acting
      sRNA, is under the positive control of the key virulence regulators HrpG and HrpX
      of Xanthomonas campestris pathovar campestris.
AB  - sRNA-Xcc1 is a trans-acting sRNA recently identified from the plant pathogenic
      bacterium Xanthomonas campestris pathovar campestris (Xcc). Here, the
      phylogenetic distribution, predicted secondary structure and regulation of
      expression of sRNA-Xcc1 were analyzed. The analysis showed (1) a total 81 sRNA
      Xcc1 homologs that are found in some bacterial strains that are taxonomically
      unrelated, belonging to the alpha-, beta-, gamma- and delta-proteobacteria (2)
      that some sRNA-Xcc1 homologs are located in a plasmid-borne transposon or near a
      transposase coding gene, (3) that sRNA-Xcc1 is encoded by a integron gene
      cassette in Xcc and sRNA-Xcc1 homologs occur in integron gene cassettes of some
      uncultured bacteria and (4) that sRNA-Xcc1 homologs have a highly conserved
      sequence motif and a stable consensus secondary structure. These findings
      strongly support the idea that sRNA-Xcc1 represents a novel family of sRNAs which
      may be originally captured by integrons from natural environments and then spread
      among different bacterial species via horizontal gene transfer, possibly by means
      of transposons and plasmids. The expression analysis results demonstrated that
      the transcription of sRNA-Xcc1 is under the positive control of the key virulence
      regulators HrpG and HrpX, indicating that sRNA-Xcc1 may be involved in the
      virulence regulation of Xcc.

PMID- 21941122
TI  - Transcriptional activators enhance polyadenylation of mRNA precursors.
AB  - 3' processing of mRNA precursors is frequently coupled to transcription by RNA
      polymerase II (RNAP II). This coupling is well known to involve the C-terminal
      domain of the RNAP II largest subunit, but a variety of other transcription
      associated factors have also been suggested to mediate coupling. Our recent
      studies have provided direct evidence that transcriptional activators can enhance
      the efficiency of transcription-coupled 3' processing. In this point-of-view, we
      discuss the mechanisms that underlie coupling, and their implications for control
      of alternative polyadenylation, which is emerging as a significant regulator of
      cell growth control.

PMID- 21941123
TI  - Abundant class of non-coding RNA regulates development in the social amoeba
      Dictyostelium discoideum.
AB  - Non-coding (nc)RNAs are important players in most biological processes. Although
      small RNAs such as microRNAs and small interfering RNAs have emerged as
      exceptionally important regulators of gene expression, great numbers of larger
      ncRNAs have also been identified. Many of these are abundant and differentially
      expressed but their functions have in most cases not been elucidated. The social
      amoeba Dictyostelium discoideum contain the ncRNAs commonly found in eukaryotes.
      In addition, we previously reported the identification of two novel classes of 42
      65 nt long stem-loop forming RNAs, Class I and Class II RNAs, with unknown
      function. In this study we have further characterized these abundant ncRNAs,
      which are down regulated during development. We have confirmed expression of 29
      Class I RNAs and experimentally verified the formation of the computationally
      predicted short conserved stem structure. Furthermore, we have for the first time
      created knockout strains for several small ncRNA genes in D. discoideum and found
      that deletion of one of the Class I RNAs, DdR-21, results in aberrant
      development. In addition we have shown that this Class I RNA forms a complex with
      one or several proteins but do not appear to be associated with ribosomes or
      polysomes. In a pull down assay, several proteins interacting with DdR-21 were
      identified, one of these has two RNA recognition motifs (RRMs). The purified RRM
      containing protein was demonstrated to bind directly and specifically to DdR-21.

PMID- 21941124
TI  - Alternative splicing at the right time.
AB  - Alternative splicing (AS) allows the production of multiple mRNA variants from a
      single gene, which contributes to increase the complexity of the proteome. There
      is evidence that AS is regulated not only by auxiliary splicing factors, but also
      by components of the core spliceosomal machinery, as well as through epigenetic
      modifications. However, to what extent these different mechanisms contribute to
      the regulation of AS in response to endogenous or environmental stimuli is still
      unclear. Circadian clocks allow organisms to adjust physiological processes to
      daily changes in environmental conditions. Here we review recent evidence linking
      circadian clock and AS, and discuss the role of Protein Arginine
      Methyltransferase 5 (PRMT5) in these processes. We propose that the interactions
      between daily oscillations in AS and circadian rhythms in the expression of
      splicing factors and epigenetic regulators offer a great opportunity to dissect
      the contribution of these mechanisms to the regulation of AS in a physiologically
      relevant context.

PMID- 21941125
TI  - Posttranscriptional regulation of miRNAs in the DNA damage response.
AB  - DNA damage response is an elaborate process in which cells react to external or
      internal DNA damaging stress. An extensive network of signaling molecules,
      complexes, and pathways has been identified in the DNA damage response. Emerging
      evidence indicates that microRNAs (miRNAs) play essential roles in the DNA damage
      and repair pathways. While much effort has been to predict in silico and verify
      miRNA target genes, little is known about how miRNAs themselves respond to DNA
      damage. Here we discuss recent studies showing whether and how miRNAs are
      regulated in the DNA damage response. MiRNA expression involves transcription of
      miRNA genes and maturation of the primary transcripts. Therefore, miRNA levels
      might be regulated in both transcription dependent and independent manners. While
      the DNA damage response is known to protect against tumorigenesis in vivo, a
      deficient response could contribute to tumorigenesis through miRNAs.

PMID- 21941127
TI  - Argonaute proteins regulate microRNA stability:  Increased microRNA abundance by
      Argonaute proteins is due to microRNA stabilization.
AB  - Argonaute proteins are key players in microRNA (miRNA) processing and function.
      Next to their role as RISC effector proteins mediating target silencing, they
      actively participate in miRNA biogenesis and increase miRNA abundance by a yet
      unidentified mechanism. It has been hypothesized that this increase in steady
      state miRNA levels might be due to a stabilizing effect of Argonaute proteins,
      but this has not been analyzed so far due to a lack of test systems. Here, we
      provide two approaches to estimate miRNA stability and factors affecting it: in
      cells lacking Ago2, endogenous miRNA guide strand degradation and half-lives can
      be assessed using Actinomycin D or alpha-Amanitin. In turn, miRNA passenger
      strands can serve as a model in wildtype cells to ascertain the impact of miRNA
      stability factors.  We provide evidence that Argonaute proteins stabilize mature
      miRNAs in a slicing-independent manner. Transcriptional inhibition reveals
      reduced half-lives of multiple endogenous miRNA guide strands in cells lacking
      Ago2. This effect is reversible upon the reconstitution of Argonaute expression.
      Correspondingly, overexpression of Argonaute proteins decelerates miRNA
      degradation and increases miRNA half-life. Taken together, this study employs two
      model systems to identify factors altering miRNA stability and provides evidence
      how Argonaute proteins post-transcriptionally elevate mature miRNA levels via
      increasing miRNA stability.

PMID- 21941126
TI  - RNA splicing control: yet another gene regulatory role for long nuclear noncoding
      RNAs.
AB  - The mammalian genome harbors a large number of long non-coding RNAs (lncRNAs)
      that do not code for proteins, but rather they exert their function directly as
      RNA molecules. LncRNAs are involved in executing several vital cellular
      functions. They facilitate the recruitment of proteins to specific chromatin
      sites, ultimately regulating processes like dosage compensation and genome
      imprinting. LncRNAs are also known to regulate nucleocytoplasmic transport of
      macromolecules. A large number of the regulatory lncRNAs are retained within the
      cell nucleus and constitute a subclass termed nuclear-retained RNAs (nrRNAs).
      NrRNAs are speculated to be involved in crucial gene regulatory networks, acting
      as structural scaffolds of subnuclear domains. NrRNAs modulate gene expression by
      influencing chromatin modification, transcription and post-transcriptional gene
      processing. The cancer-associated Metastasis-associated lung adenocarcinoma
      transcript1 (MALAT1) is one such long nrRNA that regulates pre-mRNA processing in
      mammalian cells. Thus far, our understanding about the roles played by nrRNAs and
      their relevance in disease pathways is only 'a tip of an iceberg'. It will
      therefore be crucial to unravel the functions for the vast number of long nrRNAs,
      buried within the complex mine of the human genome.

PMID- 21941129
TI  - Designer RNA-binding proteins: New tools for manipulating the transcriptome.
AB  - Post-transcriptional regulation of gene expression is ubiquitous and fundamental
      for the control of cell growth, differentiation and the complex developmental
      programs of multicellular eukaryotes. Despite this realization, the current tools
      that are available to study RNAs are limited in many respects. Recently we
      expanded the RNA recognition code of Pumilio and FBF homology (PUF) proteins,
      enabling RNA-binding proteins with programmable specificities to be designed. The
      design of proteins that can bind any RNA sequence of interest and modulate its
      function will be important to elucidate the mechanisms by which gene expression
      is controlled at the level of RNA and may provide potential therapeutics in the
      future.

PMID- 21941128
TI  - The nucleolar protein Nop19p interacts preferentially with Utp25p and Dhr2p and
      is essential for the production of the 40S ribosomal subunit in Saccharomyces
      cerevisiae.
AB  - In eukaryotes, ribosome biogenesis is a process of major interest that requires
      more than 200 factors acting coordinately in time and space. Using genetic and
      proteomic studies, most of the components have now been identified. Based on its
      nucleolar localization, we characterized the protein encoded by the open reading
      frame YGR251W, we renamed Nop19p as playing an essential role in ribosome
      biogenesis. Depletion of the Nop19p in yeast impairs pre-rRNA processing at sites
      A0, A1 and A2, leading to a strong decrease in 18S rRNA and 40S subunit levels.
      Nop19p is a component of 90S preribosomes which assembly is believed to result
      from stepwise incorporation of UTP modules. We show that Nop19p depletion does
      not impair the incorporation of UTP subcomplexes on preribosomes and conversely
      that depletion of UTP subcomplexes does not affect Nop19p recruitment on 90S
      preribosomes. TAP experiments under stringent conditions revealed that Nop19p
      interacts preferentially with the DEAH-box RNA helicase Dhr2p and Utp25p, both
      required for A 0, A 1 and A 2 cleavages. Nop19p appeared essential for the
      incorporation of Utp25p in preribosomes. In addition, our results suggest that in
      absence of Nop19p, Dhr2p remains trapped within aberrant preribosomes.

PMID- 21941130
TI  - Relation of serum levels of thrombopoietin to thrombocytopenia in extrahepatic
      portal vein obstruction versus cirrhotic children.
AB  - INTRODUCTION: In patients with portal hypertension, thrombocytopenia in
      cirrhotics and noncirrhotics is thought to be caused by sequestration and
      destruction of platelets within a large spleen, suppression of platelet
      production in the bone marrow, and decreased activity of the hematopoietic growth
      factor thrombopoietin (TPO). AIM: Determining the level of TPO in cirrhotic
      thrombocytopenic patients and correlate it to the degree of disease severity and
      platelet count. METHODS: A cross-sectional study conducted on 62 children; 25
      cases with cirrhosis, 20 patients with extrahepatic portal vein obstruction
      (EHPVO), and 17 healthy age-matched and sex-matched controls. The severity of
      liver cirrhosis was graded according to the Child-Pugh classification. TPO was
      measured using the quantitative human TPO by enzyme-linked immunosorbant assay.
      RESULTS: Serum TPO levels were significantly lower in the cirrhotic group
      compared with both EHPVO patients and healthy controls (P=0.01 for each). Both of
      the Child-Pugh B and C cirrhotic cases had significantly lower TPO levels
      compared with Child A cases (P=0.003). We found a significant positive
      correlation between platelet count and serum TPO level (r=0.56, P=0.004) in the
      cirrhotic group but not in the EHPVO group (r=0.1, P>0.05). CONCLUSIONS: TPO
      underproduction contributes to thrombocytopenia in children with cirrhosis;
      whereas in children with EHPVO, TPO production is unaffected and thrombocytopenia
      is secondary to hypersplenism. TPO receptor agonists may be useful to improve
      platelet counts in the former group.

PMID- 21941131
TI  - Impact of neutrophil recovery on oxygenation in pediatric oncology patients with
      acute hypoxemic respiratory failure.
AB  - Neutrophil recovery has been implicated in deterioration of oxygenation and
      exacerbation of lung injury in pediatric oncology patients. Our objectives were
      to determine the impact of neutrophil recovery on oxygenation in pediatric
      oncology patients with acute hypoxemic respiratory failure (AHRF) and to identify
      risk factors that result in oxygenation worsening. A cohort of 24 neutropenic
      pediatric oncology patients with AHRF in whom neutrophil recovery occurred during
      a course of mechanical ventilation was evaluated. Oxygenation index (OI) and
      PaO(2)/FiO(2) ratio showed a trend of improvement after neutrophil recovery. Mean
      PaO(2)/FiO(2) pre-recovery was 205+/-48.67 versus 225+/-72.24 postrecovery
      (P=0.08), whereas mean pre-recovery OI was 9.39+/-0.96 compared with 8.31+/-1.1
      postrecovery (P=0.078). Seven episodes (24% of the total episodes) of recovery
      were characterized by worsening of oxygenation. Tripling absolute neutrophil
      count on Day+2 compared with Day+1 postrecovery was associated with 28-fold
      increase in risk of oxygenation worsening. In conclusion, resolution of
      neutropenia lead to significant deterioration of oxygenation in 24% of episodes
      of neutrophil recovery in a pediatric oncology cohort with AHRF. Our findings
      suggest that a faster ANC increment in the 2 days after recovery is associated
      with an increased risk of oxygenation worsening.

PMID- 21941132
TI  - Acute constipation in children receiving chemotherapy for cancer.
AB  - BACKGROUND: Constipation occurs in children receiving chemotherapy for cancer but
      there are no data about prevalence, risk factors, and severity of constipation in
      this group of children. METHODS: We prospectively studied 61 children receiving
      chemotherapy for cancer. We administered questionnaires to children and parents
      and collected data on demographics, chemotherapy, and bowel movement pattern
      during chemotherapy. We used North American Society of Pediatric
      Gastroenterology, Hepatology, and Nutrition criteria for the diagnosis of
      constipation. Parental perception of constipation as a problem and impact on
      lifestyle during chemotherapy were assessed on a 0 to 3 scale with 0 being no
      problem, 1 minor, 2 significant, and 3 being a major problem. RESULTS: Thirty
      five children (57%) had acute constipation lasting for 2 or more weeks during
      chemotherapy. Several risk factors were analyzed and only combined use of
      vincristine and opiates emerged as significant risk factor for the development of
      constipation. In children with constipation, 15 of 35 parents (43%) perceived
      constipation as a major/significant problem and 8 children and their parents
      (23%) perceived constipation having a major/significant impact on lifestyle
      during chemotherapy. CONCLUSIONS: Acute constipation was diagnosed in 57% of
      children receiving chemotherapy for cancer. Combined use of vincristine and
      opiates was associated with the development of constipation. Constipation can be
      a significant problem with a negative impact on lifestyle during chemotherapy and
      needs aggressive management.

PMID- 21941133
TI  - Congenital dermatofibrosarcoma protuberans in a newborn infant with a massive
      back tumor: favorable effects of oral imatinib on the control of residual tumor
      growth.
AB  - Dermatofibrosarcoma protuberans (DFSP) is known as a very rare malignant tumor of
      the deep dermis and subcutaneous tissue. It typically develops during adolescence
      and adulthood, with pediatric and infantile cases, particularly congenital ones,
      being much less frequent. We report a neonate with congenital DFSP. A newborn
      girl presented with a massive back tumor at birth. The tumor was at first
      suspected to be infantile fibrosarcoma (IFS) after immunohistochemical analysis
      of biopsy material, although the results were not fully compatible with IFS. She
      received chemotherapy under a tentative diagnosis of IFS, but this was
      unsuccessful. Partial resection was therefore performed at the age of 8 months to
      reduce the tumor mass and to reexamine its immunohistochemical characteristics.
      Positive CD34 staining and Collagen alpha1alpha/platelet-derived growth factor
      beta chimera gene signals on analysis of the excised tumor tissues enabled a
      definitive diagnosis of DFSP. She then underwent local irradiation and was given
      a daily dose of oral tyrosine kinase inhibitor (imatinib). After almost 1 year,
      the patient is doing well without enlargement of the residual tumor.

PMID- 21941134
TI  - Primary squamous cell carcinoma of lung in a 7-year-old boy: a case report.
AB  - We are reporting a rare case of a primary squamous cell carcinoma of lung with
      skeletal metastases in a 7-year-old boy. The patient received chemotherapy with
      initial improvement but eventually died of the disease. A brief literature review
      is also presented.

PMID- 21941135
TI  - Epidemiology of febrile neutropenia in children with central nervous system
      tumor: results from a single center prospective study.
AB  - Data regarding the epidemiology febrile neutropenia during chemotherapy for
      pediatric central nervous system neoplasia are scarce. Data retrieved from a
      prospective study performed from January 2002 to December 2004 at G.Gaslini
      Children Hospital, Genoa, Italy, where analyzed to evaluate proportions, rate for
      1000 neutropenic days and etiology of fever in neutropenic children receiving
      gentle, standard, or peripheral blood stem cell transplant (PBSCT) therapy for
      central nervous system tumor. During the study duration, 243 periods of
      neutropenia (granulocyte count <1000/cmm), accounting for 3544 patient-days at
      risk, were documented in 62 children. A total of 72 febrile episodes were
      observed in 66 (27%) neutropenic periods, for a rate of 20.31. A primary febrile
      episode was observed in 10% of neutropenic periods after gentle chemotherapy, in
      30% after standard chemotherapy, and in 48% after PBSCT (P<0.0001). The rate of
      primary febrile episodes was 6.19 after a gentle chemotherapy, 27.02 after
      standard treatment, and 31.02 after PBSCT (P<0.0001). In a multivariable
      regression model, the type of chemotherapy (gentle vs. standard and PBSCT) and
      the thresholds of granulocyte count at neutropenia onset (999-501/cmm and 500
      101/cmm vs. <=100/cmm) were the only factors significantly associated with the
      development of febrile neutropenia.

PMID- 21941136
TI  - Presentation and outcomes for children with bone marrow necrosis and acute
      lymphoblastic leukemia: a literature review.
AB  - Bone marrow necrosis is a rare histopathology finding with the majority of cases
      occurring in the setting of a hematologic malignancy. This article reports a case
      of diffuse marrow necrosis in a child secondary to acute lymphoblastic leukemia
      and summarizes the clinical features and outcomes for children with bone marrow
      necrosis secondary to leukemia from 20 published reports. This review
      demonstrated that the most common presenting features were bone pain, fever,
      pancytopenia, and that outcomes were less favorable when compared with those
      without necrosis. However, contemporary literature suggests that outcomes are
      similar for children who have bone marrow necrosis secondary to leukemia when
      compared with overall survival rates for pediatric leukemia.

PMID- 21941137
TI  - Cardiac myeloid sarcoma: a case report and review of literature.
AB  - Myeloid sarcomas are rare extramedullary tumors composed of immature myeloid
      cells. Most cases are seen in childhood acute myelogenous leukemia (AML). They
      can develop at many sites, but cardiac involvement is a rare finding. We report
      the case of a 24-year-old woman who, after being in remission from AML for 10
      years, developed an isolated cardiac myeloid sarcoma.

PMID- 21941138
TI  - What I did on my summer vacation!

PMID- 21941139
TI  - Impact of hydroxyurea on perioperative management and outcomes in children with
      sickle cell anemia.
AB  - Hydroxyurea has enhanced the treatment for children with sickle cell anemia. The
      objectives of this study were to compare perioperative transfusions and outcomes
      for children taking hydroxyurea versus those not taking hydroxyurea. We
      retrospectively reviewed perioperative management and outcomes for 51 children
      with sickle cell anemia (HbSS genotype) who underwent surgery in our center
      between January 2003 and April 2008. Of the 51 patients, 30 (59%) were taking
      hydroxyurea and 21 (41%) were not taking hydroxyurea. Eight of 30 (27%) in the
      hydroxyurea group were not transfused preoperatively, 12 of 30 (40%) received a
      single transfusion and 10 of 30 (33%) received serial transfusions, compared with
      1 of 21 (5%) children in the nonhydroxyurea group who was not transfused, 2 of 21
      (10%) who received a single transfusion and 18 of 21 (85%) who received serial
      transfusions or pheresis (P=0.004; for comparison across groups). One patient not
      taking hydroxyurea developed a delayed hyperhemolytic transfusion reaction, and 2
      children taking hydroxyurea developed acute chest syndrome. Overall, children
      taking hydroxyurea had substantially fewer transfusions compared with children
      not taking hydroxyurea. Both groups of children had a low complication rate.
      Further research should be done to optimize perioperative management of children
      taking hydroxyurea.

PMID- 21941140
TI  - Changing pattern of hospital admissions of children with sickle cell disease over
      the last 50 years.
AB  - A study published in 1981 examined the causes of hospital admission for a cohort
      of children with sickle cell disease (SCD). Since that time, the incidence and
      prevalence of SCD has increased markedly in the UK, and there have been many
      changes in the management of this disease. We undertook a study examining the
      causes of hospital admission of children with SCD to the same hospital as the
      previous study, over the 2-year period from 2008 to 2009. We found that the
      numbers of children being cared for by our hospital had dramatically increased
      over the last 50 years, but rates of hospital admission had significantly fallen
      (41 hospital admissions per 100 patient-years, compared with 111.3 admissions per
      100 patient-years in the original study). This fall in admission rates is
      accounted for by 2 major components: acute painful episodes (15.7 admissions per
      100 patient-years compared with 39.3 in the previous study) and admission for
      elective blood transfusion (0.2 admissions per 100 patient-years compared with
      26.7 in the previous study). It is interesting to note that, 541 elective
      transfusions were carried out during the study period, but in a day-care setting
      rather than requiring overnight admission. This study illustrates the changes in
      management of SCD over the past 30 years, and reflects the overall trend common
      to most hospital specialties of increasing community and ambulatory care.

PMID- 21941141
TI  - Fetal hemoglobin levels in African American and Hispanic children with sickle
      cell disease at baseline and in response to hydroxyurea.
AB  - The degree of fetal hemoglobin (HbF) expression is a major determinant of
      phenotypic severity of sickle cell disease (SCD). Genetic regulation of HbF
      production is complex and can vary among ethnic groups. The pediatric sickle cell
      population at our institution is approximately half Hispanic, nearly all from the
      Dominican Republic. Hydroxyurea (HU) is the only Food and Drug Administration
      (FDA)-approved drug to ameliorate symptoms of SCD. We retrospectively compared
      baseline and HU-induced percent HbF (%HbF) in African American (AA) and Hispanic
      (H) patients aged 4 to 21 years with homozygous Sickle hemoglobin or
      HbSbeta(0)Thalassemia. No significant differences were detected in average
      baseline %HbF between AA (N=48) and H (N=58) patients (P=0.63). In the subset of
      children taking HU who reached maximum tolerated dose (MTD), no differences were
      found between the ethnic groups in laboratory response to drug, measured by %HbF
      at MTD (P=0.28), the increase in %HbF (P=0.31) or mean red cell volume (MCV)
      (P=0.93), or the MTD of HU (P=0.95). Regulation of HbF at baseline and in
      response to HU are comparable between Hispanics and African Americans at our
      center. If generalizable, our results support combining these 2 groups in future
      clinical and translational analyses focused on HbF and response to HU in this
      ethnically mixed patient population.

PMID- 21941142
TI  - Marriage and divorce among childhood cancer survivors.
AB  - Many childhood cancer survivors have psychosocial late effects. We studied the
      risks for cohabitation and subsequent separation. Through the Danish Cancer
      Register, we identified a nationwide, population-based cohort of all 1877
      childhood cancer survivors born from 1965 to 1980, and in whom cancer was
      diagnosed between 1965 and 1996 before they were 20 years of age. A sex-matched
      and age-matched population-based control cohort was used for comparison
      (n=45,449). Demographic and socioeconomic data were obtained from national
      registers and explored by discrete-time Cox regression analyses. Childhood cancer
      survivors had a reduced rate of cohabitation [rate ratio (RR) 0.78; 95%
      confidence interval (CI): 0.73-0.83], owing to lower rates among survivors of
      both noncentral nervous system (CNS) tumors (RR 0.88; 95% CI: 0.83-0.95) and CNS
      tumors (RR 0.52; 95% CI: 0.45-0.59). Male CNS tumor survivors had a
      nonsignificantly lower rate (RR 0.47; 95% CI: 0.38-0.58) than females (RR 0.56;
      95% CI: 0.47-0.68). The rates of separation were almost identical to those of
      controls. In conclusion, the rate of cohabitation was lower for all childhood
      cancer survivors than for the population-based controls, with the most pronounced
      reduction among survivors of CNS tumors. Mental deficits after cranial
      irradiation are likely to be the major risk factor.

PMID- 21941143
TI  - Intellectual impairment after treatment for medulloblastoma and astrocytoma in
      childhood: the Brazilian experience.
AB  - BACKGROUND: This study investigated the impact of posterior fossa tumors and
      their respective treatments, and the impact of clinical and sociodemographic
      variables, on the intelligence quotient (IQ) of Brazilian children. METHODS:
      Twenty patients took part in the study, of which 13 were diagnosed with
      astrocytoma (average age at evaluation 10.2 y) and 7 with medulloblastoma
      (average age at evaluation 9.2 y). The first subgroup was submitted exclusively
      to tumor resection surgery and the second subgroup underwent surgery,
      chemotherapy (Vincristine, Cisplatine, and Carmustine), and radiotherapy (total
      dose of 54 Gy). The Wechsler Intelligence Scale for Children (WISCIII) was used.
      RESULTS: The following statistically significant effects were identified:
      treatment modality on performance intelligence quotient scores (P=0.02) and
      processing speed index (PSI) (P=0.01); presence of hydrocephalus at diagnosis on
      verbal intelligence quotient (P=0.04); tumor localization on perceptual
      organization index (P=0.03); time interval between diagnosis and
      neuropsychological evaluation on PSI (P=0.05) and freedom from distraction index
      (P=0.03); and level of parental formal education on full scale IQ (P=0.02).
      CONCLUSIONS: Exposure to radiotherapy has a significant effect on processing
      speed and consequently on global intellectual capacity. The impact on
      intelligence of clinical and sociodemographic variables such as tumor
      localization, time interval between diagnosis and cognitive evaluation, and
      parental level of formal education is confirmed in the specific setting of a
      developing country.

PMID- 21941144
TI  - Skeletal morbidity in children receiving chemotherapy for acute lymphoblastic
      leukemia and its association with mineral homeostasis and duration of inpatient
      stay.
AB  - BACKGROUND: Reduced activity, older age, and abnormal bone mineral status are
      considered as important determinants of poor bone health in children with acute
      lymphoblastic leukemia (ALL). The independent contribution of these factors
      toward skeletal morbidity (SM) requires further investigation. AIM: The aim of
      this study was to investigate the influence of activity, age, and mineral status
      over the first 12 months of chemotherapy on subsequent SM. PATIENTS AND METHODS:
      The medical records of 56 children presenting with ALL between 2003 and 2007 and
      treated on UKALL2003 were reviewed for the number of inpatient days over the
      first 12 months of chemotherapy as a surrogate marker of inactivity and lack of
      well-being. Data for serum Ca, albumin, Mg, and Pho were also collected over this
      period. SM was defined as any episode of musculoskeletal pain or fractures.
      RESULTS: The median duration of inpatient days over the first 12 months of
      treatment in children with no SM was 58 days (40,100), whereas the median number
      of inpatient days during the first 12 months in those children with any SM,
      musculoskeletal pain only, or fractures only was 83 days (54,131), 81 days
      (52,119) and 91 days (59,158), respectively (P=0.003). Children with SM and
      fractures particularly had lower levels of serum Ca, Mg, and Pho compared with
      those without SM over the first 12 months of chemotherapy. There was a higher
      risk of SM in those who were diagnosed after the age of 8 years (P=0.001, odds
      ratio=16, 95% confidence interval: 3.80). Multiple regression analysis showed
      that the incidence of SM only had a significant independent association with age
      at diagnosis (P=0.001) and the number of inpatient days (P=0.03) over the first
      12 months (r=23). All children who were diagnosed after the age of 8 years with
      an inpatient stay of more than 75 days, in the first 12 months of the
      chemotherapy (n,14) children had some form of SM (odds ratio=64). CONCLUSIONS:
      The incidence of SM in children receiving chemotherapy for ALL is associated with
      a higher likelihood of being older and having longer periods of inpatient stay.
      The close link between age and changes in bone mineral status may be one
      explanation for the increased bone morbidity in ALL children.

PMID- 21941145
TI  - Barriers to the enrollment of children in the Children's Oncology Group study of
      very low risk Wilms tumor: a report from the Children's Oncology Group.
AB  - Very low risk Wilms tumor is defined by favorable histology, age below 2 years,
      tumor weight less than 550 g, and stage I. The Children's Oncology Group is
      currently studying a nephrectomy-only strategy for these patients but the accrual
      rate is slightly below expected. Twenty-five of 31 institutions responded with
      reasons by physicians and/or parents for electing not to participate. Parents
      were primarily concerned with the experimental nature of the study, whereas
      physicians were concerned about accurate staging, with some overlap. We point out
      the necessity of assessing these concerns in predicting feasibility of and
      accrual to a therapy reduction study.

PMID- 21941146
TI  - Evaluation of eIF4E expression in an osteosarcoma-specific tissue microarray.
AB  - The ability to define osteosarcoma (OS) patients at greatest risk for metastatic
      progression and nonresponsiveness to conventional therapy is currently not
      possible. Such biomarkers are needed to predict overall prognosis, probability of
      metastases at diagnosis, and response to chemotherapy. The tissue microarray
      (TMA) serves as a powerful tool for detecting and validating protein biomarkers
      across a variety of patients. We constructed a novel outcome-linked TMA to add to
      and address shortcomings of currently available OS tissue resources. To test the
      use of our TMA, we surveyed the expression of eukaryotic initiation factor 4E
      (eIF4E) in OS patients using immunohistochemistry. Aberrant regulation of
      translation initiation is a feature of many cancers. eIF4E is central to
      initiation of protein synthesis. Its expression and activity have been implicated
      in tumor formation and potentially malignant and/or metastatic progression in
      some carcinomas. We found that eIF4E was uniformly expressed in OS patient
      samples. No association was found between eIF4E and outcome in OS patients. This
      novel OS TMA provided a facile mechanism to assess the role of a relevant protein
      biomarker in OS.

PMID- 21941147
TI  - Differential profiles of microRNAs in retinoblastoma cell lines of different
      proliferation and adherence patterns.
AB  - Retinoblastoma (RB) is the most common intraocular malignant tumor in childhood.
      To investigate differential expression of microRNAs (miRNAs) in RB cell lines of
      different growth patterns: SNUOT-Rb1 with adherent and more rapid growth and Y79
      with nonadherent and slower growth, miRNA microarray was performed. Common mRNA
      targets of each miRNA were extracted from 4 web-based databases: TargetScan,
      miRanda, RNAhybrid, and PicTar. Biological functions of target genes were
      predicted with the PANTHER Classification System. We identified 39 differentially
      expressed miRNAs between 2 cell lines: 22 were upregulated in SNUOT-Rb1 cells,
      and the other 17 were overexpressed in Y79 cells. More than half of top 10 mRNA
      targets of hsa-miR-10b, hsa-miR-29a, hsa-miR-29b, hsa-miR-29c, and hsa-let-7c in
      SNUOT-Rb1 cells and hsa-miR-34a, hsa-miR-34c-5p, hsa-miR-124, hsa-miR-135b, hsa
      miR-142-5p, and hsa-let-7i in Y79 cells were related with biological processes,
      which could affect the growth patterns of cells: cell adhesion, cell cycle, cell
      death, and cell division. On the basis of the data from the target analysis of
      each miRNA, we found out several miRNAs, which were differentially expressed and
      had targets of possible impact on progression of RB. From these analyses, we
      suggest that some differential miRNAs could have roles in miRNA-targeted
      treatments on RB.

PMID- 21941148
TI  - Complete resolution of sickle cell chronic pain with high dose vitamin D therapy:
      a case report and review of the literature.
AB  - With age, individuals with sickle cell disease (SCD) experience daily chronic
      pain. Vitamin D deficiency (VDD) can result in chronic pain, osteoporosis,
      fractures, and muscle weakness. Several studies report a high prevalence of VDD
      in SCD; however, the clinical correlates have not been well described. We
      describe a case of SCD chronic pain associated with profound VDD, osteoporosis,
      and osteonecrosis. Treatment with high-dose vitamin D resulted in complete
      resolution of chronic pain symptoms and improvement in bone density. Randomized
      studies of vitamin D in SCD may help elucidate its role in the management of
      chronic pain and bone disease.

PMID- 21941149
TI  - Diagnosis of autoimmune neutropenia by neutrophil-bound IgG and IgM antibodies.
AB  - Autoimmune neutropenia (AIN) in infancy is caused by antineutrophil (granulocyte
      specific) autoantibodies. These antibodies are rarely found in circulation
      because their serum levels are extremely low. We hypothesized that a direct
      granulocyte immunofluorescence test (D-GIFT) that enables us to detect neutrophil
      bound autoantibodies consisting of both immunoglobulin (Ig) G and IgM has better
      diagnostic value than the detection of circulating autoantibodies. Whole blood
      (100 MUL) was obtained from 50 infants with AIN, 12 infants with transient
      neutropenia, and 37 control infants. D-GIFT was performed using both fluorescein
      isothiocyanate-conjugated antihuman IgG Fc portion monoclonal antibodies and
      fluorescein isothiocyanate antihuman IgM monoclonal antibodies. Results were
      assessed as relative fluorescence intensity (RFI). The RFIs of antineutrophil IgG
      bound and antineutrophil IgM-bound cells in patients with AIN were significantly
      higher than those in patients with transient neutropenia and in controls.
      Positive results, as assessed by RFI scores of more than 1.81 in either
      antineutrophil IgG-bound or antineutrophil IgM-bound cells, showed the
      sensitivity and specificity of D-GIFT, and the areas under the receiver operating
      characteristic curve (0.98, 0.98, and 0.997, respectively) in the diagnosis of
      AIN. D-GIFT detecting both neutrophil-bound IgG autoantibodies and IgM
      autoantibodies has discriminatory power for identifying patients with AIN and,
      therefore, can be a useful diagnostic test.

PMID- 21941150
TI  - Brain atrophy caused by vitamin B12-deficient anemia in an infant.
AB  - Vitamin B12 deficiency in infants often presents with nonspecific hematological,
      gastrointestinal, and neurological manifestations. It is usually caused by
      inadequate intake, abnormal absorption, or congenital disorders of vitamin B12
      metabolism, including transport disorders. We describe a vitamin B12-deficient
      infant with severe anemia who was breastfed. His mother had undiagnosed vitamin
      B12 deficiency having undergone total gastrectomy 18 years earlier. The infant
      developed normally after taking vitamin B12. It is important to suspect vitamin
      B12 deficiency in mothers who have undergone gastrectomy. Early diagnosis and
      treatment of vitamin B12 deficiency in infants is important and will help improve
      long-term prognosis.

PMID- 21941151
TI  - Influenza A (H1N1) in a pediatric patient with newly diagnosed acute
      promyelocytic leukemia and invasive pulmonary aspergillosis.
AB  - Influenza A (H1N1) pandemic reached its peak in Europe in autumn 2009. H1N1
      infection can be a serious complication in patients with comorbidity or
      immunodepression. Here, we report of a boy with newly diagnosed acute
      promyelocytic leukemia with a very severe respiratory distress caused by
      influenza A (H1N1) infection in pulmonary aspergillosis, successfully treated
      with antifungal therapy, oseltamivir, and extracorporeal membrane oxygenation.

PMID- 21941152
TI  - Cryptosporidiosis in children with acute lymphoblastic leukemia on maintenance
      chemotherapy.
AB  - Cryptosporidium is recognized as a cause of diarrhea associated with a high
      mortality in immunocompromised patients. We report on 2 pediatric cases of
      cryptosporidiosis during maintenance chemotherapy of acute lymphoblastic
      leukemia. The patients presented severe diarrheas, 1 of them was complicated by a
      cholangitis. Withdrawal of immunosuppressive treatments and adjunction of an
      adequate antiparasitic treatment cured the Cryptosporidium infection in both
      cases.

PMID- 21941153
TI  - Demographic characteristics and behavioral risk factors of HIV infection and
      association with survival among individuals 50 years or older.
AB  - OBJECTIVES: To investigate the association of socio-behavioral characteristics
      and viro-immunological status with survival in a cohort of HIV-infected
      individuals by age in South Carolina (SC). METHODS: Logistic regression was used
      to compare the characteristics of individuals' >=50 years old to individuals 20
      49 years old at HIV diagnosis who were reported to SC enhanced HIV/AIDS Reporting
      System (eHARS) from January 1998 to December 2009. Cox proportional hazards
      analysis was used to examine the time to death after HIV diagnosis over the study
      period. RESULTS: Of the 7531 participants, 1204 (16%) were >=50 years old.
      Multivariable analyses suggested that individuals >=50 years old were more likely
      to have simultaneous AIDS (aOR 1.80, 95% CI 1.54-2.10). For individuals >=50
      years old, the risk of death was more than three times when compared to the
      younger age group (HR: 3.46, 95% CI 2.27, 5.30). CONCLUSION: Routine HIV
      screening may decrease late-stage diagnosis and improved linkage to care may
      decrease mortality in older adults.

PMID- 21941154
TI  - "Murder or mercy?" An innovative module helping UK medical students to articulate
      their own ethical viewpoints regarding end-of-life decisions.
AB  - This module was designed to equip UK medical students to respond ethically and
      sensitively to requests encountered as qualified doctors regarding euthanasia and
      assisted dying. The aim was to expose students to relevant opinions and
      experiences and provide opportunities to explore and justify their own views and
      rehearse ethical decision making in a safe learning environment.The module is
      delivered by a multidisciplinary team, providing students with the working
      knowledge to actively discuss cases, articulate their own views and practice
      ethical reasoning. Visits to intensive care units, palliative care wards and
      hospices are integrated with theory. Student assessment comprises a dissertation,
      debate and reflection. Module impact was evaluated by analysis of student
      coursework and a questionnaire.Students greatly appreciated the clinical context
      provided by the visits and opportunities to apply ethical reasoning to cases and
      debate issues with peers. They reported increased discernment of the ethical and
      legal position and practical considerations and greater awareness of the range of
      professional and lay viewpoints held. Many participants were less strongly in
      favor of euthanasia and assisted dying on module completion than at the outset,
      but all of them believed they were better equipped to justify their own viewpoint
      and respond to patient requests. The multi-disciplinary nature of this course
      helps to prepare students to deal effectively and sensitively with ethical
      dilemmas they will encounter in their medical career. Use of an integrated,
      learner-centred approach equips students to actively engage with their peers in
      discussion of such issues and to formulate and defend their own position.

PMID- 21941155
TI  - Commentary on "murder or mercy?".

PMID- 21941156
TI  - Retrospective chart review of children with type 2 diabetes mellitus evaluating
      the efficacy of metformin vs. insulin vs. combination insulin/metformin.
AB  - OBJECTIVES: Type 2 diabetes mellitus is a growing problem in pediatrics and there
      is no consensus on the best treatment. We conducted this chart review on newly
      diagnosed pediatric patients with type 2 diabetes mellitus to compare the effect
      of treatment regimen on body mass index (BMI) and hemoglobin A1c over a 6-month
      period. METHODS: We conducted a retrospective chart review on patients with type
      2 DM who presented to Nationwide Children's Hospital. Data were collected on
      therapy type, BMI, and hemoglobin A1c over a 6-month follow-up. Therapy type was
      divided into metformin, insulin, or combination insulin and metformin. 1,997
      charts were reviewed for inclusion based on ICD-9 codes consistent with a
      diagnosis of diabetes, abnormal oral glucose tolerance test, or insulin
      resistance. RESULTS: Of the 47 charts eligible for the review, 26 subjects were
      treated with metformin 1000-1500 mg daily, 14 patients were treated with insulin
      therapy, and 7 patients were treated with a combination of insulin and metformin
      therapy. At baseline, the only significant difference among groups was A1c (P =
      0.012). In regression analysis with baseline A1c as a covariate, the only
      predictor of change in A1c over time was the A1c at onset (P < 0.001). Therapy
      type was not predictive of change (P = 0.905). Regression analysis showed a
      greater BMI at onset predicted a greater decrease in BMI (P = 0.006), but therapy
      type did not predict a change (P = 0.517). CONCLUSION: Metformin may be as
      effective as insulin or combination therapy for treatment of diabetes from onset
      to 6-month follow-up.

PMID- 21941157
TI  - Evaluation of multi-drug therapy for leprosy in the United States using daily
      rifampin.
AB  - OBJECTIVES: To evaluate the occurrence of relapse of multibacillary leprosy after
      multi-drug treatment including daily rifampin. METHODS: A retrospective review
      was performed utilizing data from the National Hansen's Disease Program (NHDP) on
      patients with leprosy treated and followed from 1988-1997 who received multi-drug
      therapy including daily rifampin. The occurrence of relapse in this cohort was
      measured, and demographic data and various clinical variables were also gathered.
      RESULTS: Ultimately, 158 cases fulfilled the eligibility criteria. 77% of cases
      were multibacillary patients and were treated with 2 or 3 drug protocols at rates
      of 36% and 35% before and after 1992, respectively. Only one case of relapse was
      found, and this patient underwent 2-drug therapy versus 3-drug therapy.
      CONCLUSION: These data are remarkable for the absence of relapse with daily
      rifampin, as contrasted with the published experience using the WHO protocol with
      monthly rifampin.

PMID- 21941158
TI  - Prevalence of criminal behaviors in an internal-medicine-resident clinic
      population.
AB  - OBJECTIVE: Few, if any, US studies have examined rates of criminal behaviors
      among patients in clinical samples. According to findings from non-US studies,
      mostly in psychiatric samples, rates of criminal behavior are higher than in the
      general population. In this study, we examined the prevalence of criminal
      behaviors in an internal medicine outpatient sample from a resident-provider
      clinic. METHOD: In a consecutive sample of internal medicine outpatients, 380
      participants were surveyed in October of 2010 regarding 27 criminal offenses as
      delineated by the crime categorization schema used by the Federal Bureau of
      Investigation. RESULTS: In this sample, 22.1% reported at least one criminal
      charge. The most commonly self- reported criminal charge was driving under the
      influence of alcohol or drugs (10.3%), followed by disorderly conduct (7.1%),
      drug abuse violations (5.8%), simple assault (5.3%), drunkenness (4.5%), and
      aggravated assault (3.2%). CONCLUSIONS: Like previous non-US studies among
      psychiatric samples, there appears to be a higher prevalence of criminal behavior
      among outpatients in an internal medicine training clinic than in the general
      population. These behaviors may be inter-related through alcohol/substance-use
      disorders.

PMID- 21941159
TI  - Prevalence of criminal behaviors in an internal-medicine-resident clinic
      population.

PMID- 21941160
TI  - Pressure modes of invasive mechanical ventilation.
AB  - Pressure modes of invasive mechanical ventilation generate a tidal breath by
      delivering pressure over time. Pressure control ventilation (PC) is the
      prototypical pressure mode and is patient- or time-triggered, pressure-limited,
      and time-cycled. Other pressure modes include pressure support ventilation (PSV),
      pressure-regulated volume control (PRVC, also known as volume control plus
      [VC+]), airway pressure release ventilation (APRV), and biphasic ventilation
      (also known as BiLevel). Despite their complexity, modern ventilators respond to
      patient effort and respiratory system mechanics in a fairly predictable fashion.
      No single mode has consistently demonstrated superiority in clinical trials;
      however, empiric management with a pressure mode may achieve the goals of patient
      ventilator synchrony, effective respiratory system support, adequate gas
      exchange, and limited ventilator-induced lung injury.

PMID- 21941161
TI  - Pressure modes of invasive mechanical ventilation.

PMID- 21941162
TI  - Generic psychotropic medications: issues of cost-effectiveness and patient
      benefit.
AB  - Since the implementation of managed care, clinicians have struggled with ways to
      provide optimal treatment in a cost-effective manner. With the rising cost of
      medications, generic substitutes appear to be an answer. Some medications have
      proven to be less effective in generic form. Consumers may be wary of generics.
      However, when financially motivated, many people choose generic over brand-name
      products. With the hope of finding effective medications with fewer side effects,
      drug companies continue to spend money to find the best solutions. Research in
      medication efficacy is costly, which is handed over to the consumer. Benefits and
      efficacy of generics will be discussed.

PMID- 21941163
TI  - Generic versus brand name drugs in psychopharmacology: a pharmacoeconomic
      perspective.

PMID- 21941164
TI  - Mycobacterial immune restoration disease:  one symphony, two or many?

PMID- 21941165
TI  - Abacavir increases platelet reactivity via competitive inhibition of soluble
      guanylyl cyclase.
AB  - OBJECTIVE: To provide a molecular mechanism that explains the association of the
      antiretroviral guanosine analogue, abacavir, with an increased risk of myocardial
      infarction. DESIGN: Drug effects were studied with biochemical and cellular
      assays. METHODS: Human platelets were incubated with nucleoside analogue drugs ex
      vivo. Platelet activation stimulated by ADP was studied by measuring surface P
      selectin with flow cytometry. Inhibition of purified soluble guanylyl cyclase was
      quantified using an ELISA to measure cGMP production. RESULTS: Pre-incubation of
      platelets in abacavir significantly increased activation in response to ADP in a
      time and dose-dependent manner. The active anabolite of abacavir, carbovir
      triphosphate, competitively inhibited soluble guanylyl cyclase activity with a
      K(i) of 55 MUmol/l. CONCLUSION: Abacavir competitively inhibits guanylyl cyclase,
      leading to platelet hyperreactivity. This may explain the observed increased risk
      of myocardial infarction in HIV patients taking abacavir.

PMID- 21941166
TI  - High-level, lasting antiviral immunity induced by a bimodal AIDS vaccine and
      boosted by live-virus exposure:  prevention of viremia.
AB  - OBJECTIVE: To characterize the correlates of protection from systemic infection
      in a vaccinated rhesus macaque, RAt-9, which had been challenged sequentially
      with two related clade C simian/human immunodeficiency viruses (SHIV-Cs) yet
      remained aviremic for more than 5 years despite indirect evidence of cryptic
      infection. DESIGN: To measure long-term anti-SHIV-C immunity, host genetics and
      gene-expression patterns for protective correlates. METHODS: Long-term immune
      reactivity was evaluated and identification of virus in RAt-9 was attempted by RT
      PCR analysis of concentrated plasma and blood transfer to CD8(+) cell-depleted
      infant macaques. Full MHC genotyping of RAt-9, TRIM5alpha and KIR3DL allelic
      expression analysis of PBMC, and microarray gene expression analysis were
      performed. RESULTS: All attempts to detect/isolate virus, including blood
      transfer to CD8(+) cell-depleted infant rhesus macaques, were negative, and the
      animal maintained normal levels of memory CD4(+) T cells in both peripheral blood
      and gut tissues. However, RAt-9 maintained high levels of anti-SHIV-C humoral and
      cellular immunity, including reactivity to nonvaccine neoantigens (Nef and Rev),
      up to 63 months postinitial challenge, suggesting chronic sub-threshold
      infection. RAt-9 expressed the Mamu A*001 allele negative for B*008 and B*017,
      had a B13 serotype, and had increased expression of killer-cell immunoglobulin
      like receptors (KIRs) previously linked to favorable outcomes of lentiviral
      infection. Elements of the gene expression profiling coincided with genotyping
      results. RAt-9 also displayed CD8 cell noncytotoxic antiviral response (CNAR)
      activity. CONCLUSION: Monkey RAt-9 is the first example of a virus-exposed,
      persistently aviremic animal that has maintained long-term, high-level cellular
      and humoral antiviral immunity in the absence of an identifiable cryptic
      reservoir.

PMID- 21941168
TI  - The experience of caregiving:  differences between behavioral variant of
      frontotemporal dementia and Alzheimer disease.
AB  - OBJECTIVE: To examine caregiver strain, depression, perceived sense of control,
      and distress from patient neuropsychiatric symptoms in family caregivers of
      persons with Alzheimer disease (AD) and behavioral variant of frontotemporal
      dementia (bvFTD) and determine whether group differences exist. METHODS: Family
      caregivers were recruited from the Memory and Aging Center in San Francisco,
      California. Analyses of cross-sectional data on 53 family caregivers (AD = 31,
      bvFTD = 22) were performed. The Mann-Whitney U test was used to contrast groups.
      RESULTS: There were statistically significant differences between the AD and
      bvFTD caregivers in strain, distress, and perceived control but not in
      depression. On average, bvFTD caregivers experienced greater strain and distress,
      more depressive symptoms, and lower perceived control. CONCLUSIONS: Findings
      support that experiences of AD and bvFTD caregivers may differ. Further study is
      needed to identify possible explanatory factors for these group differences.

PMID- 21941169
TI  - Emotional stroop performance in older adults:  effects of habitual worry.
AB  - OBJECTIVE: In clinically anxious individuals, selective attention to negative
      cues in the environment may perpetuate a vicious cycle of emotional dysfunction.
      However, very little is known regarding the role of negative attentional bias in
      anxious older adults. There is evidence that in older adults without clinical
      anxiety, the opposite bias (toward positive, and away from negative, emotional
      material) is present. We explored how these age-related changes in emotional
      processing interact with anxiety. METHOD: Sixty older adults (age 60+) completed
      the emotional Stroop (eStroop) task, a widely used measure of attentional bias,
      which requires rapid identification of the color in which neutral and emotional
      words are printed. Participants were stratified into high-, mid-, and low-worry
      groups on the basis of a self-report measure, the Penn State Worry Questionnaire.
      RESULTS: The high-worry group exhibited a bias toward threat-related words
      whereas the low- and mid-worry groups showed a bias away from threat-related
      words. By contrast, the low- and mid-worry groups showed a bias toward positive
      words, potentially consistent with an established positivity effect in older
      adults whereas the high-worry group showed a bias away from positive items.
      CONCLUSION: Older adults who worry frequently exhibit a pattern of eStroop
      performance that is broadly consistent with the younger adult literature,
      suggesting that selective attention toward threat-related information may be seen
      as a relevant factor in older, as in younger, anxiety.

PMID- 21941170
TI  - Pancreatic cancer cell and microparticle procoagulant surface characterization: 
      involvement of membrane-expressed tissue factor, phosphatidylserine and
      phosphatidylethanolamine.
AB  - Advanced pancreatic cancer is associated with a high risk of patients developing
      venous thromboembolism. This increased risk is thought to be tumour-driven and
      associated with tissue factor (TF) and microparticles. The aim of this study was
      to investigate the role of TF and phospholipid expression in the procoagulant
      properties of pancreatic cell lines and microparticles. Pancreatic cancer cell
      lines (MIA-PaCa-2, ASPC-1 and CFPAC-1) were assessed for expression of TF and
      microparticle release. Procoagulant potential was determined by a prothrombin
      time assay. Cell surface expression of TF was highest in CFPAC-1, with low
      expression on ASPC-1 and little/no expression on MIA-PaCa-2. Clotting time (CT)
      was cell number and TF-dependent (P < 0.001). Blocking of TF resulted in slower
      CT for CFPAC-1 and ASPC1 and prevented clotting in MIA-PaCa-2. Microparticles
      were shown to be procoagulant and the majority of procoagulant potential could be
      removed by passing cell-free media through a 0.1 MUm filter. A dose-dependent CT
      was observed in both ASPC-1 and CFPAC-1 cell-free media. Furthermore, addition of
      duramycin prevented microparticle-supported coagulation. The data presented
      suggest a key role for cell and microparticle surface-expressed TF and
      phospholipids in coagulation and highlight duramycin-mediated disruption of
      clotting.

PMID- 21941167
TI  - Initial viral decay to assess the relative antiretroviral potency of protease
      inhibitor-sparing, nonnucleoside reverse transcriptase inhibitor-sparing, and
      nucleoside reverse transcriptase inhibitor-sparing regimens for first-line
      therapy of HIV infection.
AB  - OBJECTIVES: To evaluate the effects of sex and initial antiretroviral regimen on
      decay of HIV-RNA and virologic outcome. METHODS: We conducted a viral dynamics
      substudy of A5142, a trial comparing lopinavir (LPV)/ritonavir with efavirenz
      (LPV/EFV) versus LPV and two nucleoside reverse transcriptase inhibitor (NRTI)
      (LPV) versus EFV and two NRTI (EFV) in antiretroviral (ARV)-naive individuals.
      HIV-RNA was measured at days 2, 10, and 14 in the substudy and at weeks 1, 4, and
      8 in A5142 participants. Two-phase viral decay was estimated in the substudy with
      biexponential mixed-effects modeling and compared using Wilcoxon tests. Week 1
      HIV-RNA change was assessed as a predictor of virologic failure (HIV-RNA above 50
      or 200  copies/ml) at weeks 24-96 using logistic regression. RESULTS: Sixty-eight
      individuals were enrolled in the substudy (median HIV-RNA 4.9 log(10) 
      copies/ml). Median rates of phase 1 viral decay by treatment were 0.61(EFV/LPV),
      0.53(LPV), and 0.63(EFV) per day. Phase 1 decay was significantly faster for EFV
      than LPV (P = 0.023); other comparisons were not significant (P > 0.11). Viral
      decay did not differ by sex (P = 0.10). Week 1 HIV-RNA change, calculated in 571
      participants of A5142, was greater for the EFV (median -1.47 log(10)  copies/ml)
      than either the LPV/EFV or LPV groups (-1.21 and -1.16 log(10 ) copies/ml,
      respectively; P < 0.001). Week 1 HIV-RNA change was associated with virologic
      failure above 50  copies/ ml at weeks 24 and 48 (P < 0.018), but not above 200 
      copies/ml at these time points or for any value at week 96. CONCLUSION: Phase 1
      decay was faster for EFV than LPV or LPV/EFV. Week 1 HIV-RNA change predicted
      virologic outcome up to week 48, but not at week 96.

PMID- 21941171
TI  - Chameleon-like appearance of immunotactoid keratopathy.
AB  - PURPOSE: To demonstrate 5 different patterns of immunotactoid keratopathy (ITK)
      in monoclonal gammopathy of undetermined significance (MGUS) that can mimic
      hereditary and degenerative disorders. First follow-up of 1 female patient was
      performed. METHODS: Colored slit-lamp photodocumentation of 6 MGUS light kappa
      patients with different types of ITK, one patient with a follow-up of 7 years.
      Systemic and serological examinations of all 6 patients were performed. RESULTS:
      The systemic and serological examinations disclosed an MGUS light kappa in all 6
      patients. The 7-year follow-up of case 2 showed a reduction of lattice-like
      opacity to moderate diffuse corneal opacity. Corneal opacity patterns of the 6
      patients were as follows: pattern 1, crystalline-like; pattern 2, lattice-like;
      pattern 3, peripheral granular-like; pattern 4, peripheral band-like; and
      patterns 5 and 6, peripheral patch-like. CONCLUSIONS: ITK of MGUS can mimic
      cystinosis, Schnyder corneal dystrophy (CD), pre-Descemet CD, lattice CD,
      granular CD, arcus lipoides, lecithin-cholesterol acyltransferase deficiency,
      gelatinous drop-like CD, and Salzmann nodular degeneration. ITK can be the first
      symptom of MGUS. An annual internal check of MGUS is recommended because of
      occurrence of a systemic monoclonal gammopathy in 20% of cases.

PMID- 21941172
TI  - Modified surgical technique for improving donor adherence in DSAEK in the aphakic
      vitrectomized eye.
AB  - We describe a modified technique for performing Descemet stripping automated
      endothelial keratoplasty (DSAEK) in a patient with aphakia and vitrectomized eye.
      A 72-year-old woman presented with corneal decompensation after a complicated
      cataract surgery and a subsequent vitreoretinal procedure. Before commencing
      DSAEK, a pars plana infusion cannula was inserted 3 mm from the limbus. The
      infusion fluid in the vitrectomized posterior segment helped circumvent potential
      complications, such as recurrent globe collapse, posterior dislocation of the
      donor disc, and loss of air tamponade. Increasing the infusion pressure allowed
      the surgeon to levitate the air bubble, effectively vaulting the donor disc
      against the recipient host bed. This modified approach helps overcome the
      possible complications of DSAEK in aphakic vitrectomized eyes and enhances donor
      adherence.

PMID- 21941173
TI  - Elevated intraocular pressure-induced interlamellar stromal keratitis occurring 9
      years after laser in situ keratomileusis.
AB  - Elevated intraocular pressure-induced interlamellar stromal keratitis (PISK) is
      an entity of interface haze usually occurring weeks to months after laser in situ
      keratomileusis (LASIK) that is associated with elevated intraocular pressures and
      worsening with steroid treatment. There is evidence that this interface haze is
      the result of abnormal fluid dynamics that occur in the cornea after LASIK. We
      present a case of pressure-induced interlamellar stromal keratitis occurring 9
      years after LASIK in the setting of anterior uveitis. This case emphasizes the
      importance of considering such diagnoses as pressure-induced interlamellar
      stromal keratitis in the differential diagnosis when presented with a patient
      with corneal haze and a history of LASIK.

PMID- 21941174
TI  - Certolizumab pegol therapy for rheumatoid arthritis-associated scleritis.
AB  - PURPOSE: To report the successful treatment of rheumatoid arthritis (RA)
      associated scleritis with the tumor necrosis factor alpha antagonist certolizumab
      pegol. METHODS: Retrospective case report of therapeutic interventions for a 47
      year-old woman with scleritis and RA. After not tolerating treatment with other
      tumor necrosis factor alpha inhibitors and rituximab, or after that treatment
      failed, certolizumab pegol was administered in an attempt to achieve better
      control of her disease process. RESULTS: Six months after beginning the new
      therapy, it was well-tolerated and the patient's RA and scleritis were quiescent.
      CONCLUSIONS: Certolizumab pegol may successfully treat RA-associated scleritis,
      even in a patient who has not tolerated therapy with other tumor necrosis factor
      alpha antagonists or in whom that treatment has failed.

PMID- 21941175
TI  - A significant drug-drug interaction detected through corneal examination:
      resolution of cornea verticillata while using amiodarone.
AB  - PURPOSE: To describe a patient with resolution of cornea verticillata while still
      using amiodarone as a result of a drug interaction lowering serum levels of
      amiodarone. METHODS: An 83-year-old retired physician with long-standing cornea
      verticillata was noted to have complete resolution of cornea verticillata on a
      routine follow-up eye examination. The patient reported complete compliance with
      using amiodarone daily, with no recent changes in dosage or formulation. Despite
      this, he reported a recent increase in the frequency of palpitations. He had
      recently started rifampin for treatment of tuberculosis. RESULTS: Serum
      amiodarone and desethylamiodarone levels were obtained and found to be below
      therapeutic range. After rifampin was discontinued, serum amiodarone and
      desethylamiodarone levels increased to a therapeutic range and cornea
      verticillata returned after 4 months. CONCLUSIONS: In patients currently using
      amiodarone, clearing of cornea verticillata should alert the ophthalmologists to
      the possibility of decreased serum amiodarone levels.

PMID- 21941176
TI  - Histologic findings of bevacizumab-treated human conjunctiva in Stevens-Johnson
      syndrome.
AB  - PURPOSE: To present the histopathologic findings of the conjunctiva of a patient
      with Stevens-Johnson syndrome (SJS)-associated ocular surface neovascularization
      (OSN) after topical bevacizumab (TB) treatment. METHODS: A 40-year-old man with
      SJS and OSN received topical bevacizumab (25 mg/mL) for 12 months in 1 eye in
      addition to previously bilaterally administered tobramycin/dexamethasone eye
      drops. He subsequently underwent bilateral release of symblephara to relieve
      diplopia. Conjunctival samples from both eyes were obtained for histopathologic
      study. RESULTS: The TB-untreated conjunctiva manifested marked stromal
      vascularization (approximately 4-5 blood vessels per high-power field) and
      perivascular mononuclear inflammatory cells. The TB-treated eye manifested with
      markedly less stromal vascularization (approximately 1-2 vessels per high-power
      field) in the conjunctiva and absence of perivascular inflammatory cells.
      CONCLUSIONS: These histopathologic findings provide evidence that TB penetrates
      the ocular surface, induces regression of OSN, and possibly moderates ocular
      inflammation. TB may be a useful additional treatment for OSN among patients with
      SJS.

PMID- 21941177
TI  - Should the knowledge gained from the Frequent Hemodialysis Network (FHN) trials
      change dialysis practice?
AB  - PURPOSE OF REVIEW: This review summarizes findings of the recently published
      Frequent Hemodialysis Network (FHN) Daily and Nocturnal trials, and speculates
      about potential mechanisms causing differences in the results and implications
      for changes in clinical practice. RECENT FINDINGS: The FHN Daily and the
      Nocturnal trial differed in time of day, location and length of treatment, and
      also in degree of residual renal function as exclusion criterion.The two
      coprimary outcomes were a composite of mortality and change in left ventricular
      mass and physical component score of the Research and Development (RAND) Short
      Form (SF)-36, which both improved significantly in the Daily trial, but not in
      the Nocturnal trial. Secondary outcomes, such as interdialytic weight gain, blood
      pressure and predialysis serum phosphorus improved significantly in both trials.
      The results of the Daily trial were comparable to those in the literature
      describing improvements by salt restriction and volume control. Reasons for the
      lack of significance in the results of the Nocturnal trial are under intensive
      investigation at this point. SUMMARY: Salt restriction, improved volume control,
      and better phosphate control might prove to be important for better treatment of
      patients on hemodialysis. Additional analyses will provide further insight and
      implications for clinical practice.

PMID- 21941178
TI  - Predictive modeling for improved anemia management in dialysis patients.
AB  - PURPOSE OF REVIEW: This review will explore the basic assumptions needed to
      perform predictive modeling of hemoglobin response to erythropoiesis stimulating
      agents (ESAs) and summarize the current literature in the area so that the
      practitioner can incorporate these tools as part of an improved anemia management
      process. RECENT FINDINGS: During the last year, several publications have
      demonstrated some advances in the field that may improve anemia management. The
      first of these was the publication of a randomized, controlled clinical trial of
      model predictive control in the dosing of erythropoietin. This work showed that
      hemoglobin variability can be decreased using predictive models of hemoglobin
      response. The second publication is potentially more interesting in the long run,
      as new markers of erythropoietin response were identified in a well-defined
      population of patients. SUMMARY: Predictive models of hemoglobin response improve
      anemia management by decreasing hemoglobin variability. This will result in more
      patients within the target range. Coupling these tools with new biomarkers of
      hemoglobin response has the potential to dramatically improve anemia management.

PMID- 21941179
TI  - Creatinine-based formulae for estimating glomerular filtration rate:  is it time
      to change to chronic kidney disease epidemiology collaboration equation?
AB  - PURPOSE OF REVIEW: To discuss the most commonly used creatinine-based glomerular
      filtration rate (GFR) estimating equations, focus on the modification of diet in
      renal disease (MDRD) equation and the chronic kidney disease epidemiology
      collaboration (CKD-EPI) equation, and review studies that have directly compared
      their performance, estimated the prevalence of chronic kidney disease (CKD), and
      assessed prognosis related to each equation. RECENT FINDINGS: The CKD-EPI
      equation was published in 2009 and appears to be more generalizable and accurate
      for estimating GFR in comparison with the MDRD equation. Compared with the MDRD
      study equation, the CKD-EPI equation results in a lower prevalence of CKD and a
      more accurate assessment of prognosis, particularly when estimated GFR is greater
      than 60 ml/min/1.73 m(2). SUMMARY: The CKD-EPI equation appears to be a more
      generalizable and accurate equation for estimating GFR in comparison with the
      MDRD equation. Additional studies in subgroups such as the elderly, in the
      general population where individuals are not selected for being at high risk of
      CKD, and across different race/ethnic populations are needed in order to further
      generalize these findings. In the meantime, there is accumulating evidence to
      support the recommendation that the CKD-EPI equation should replace the MDRD
      equation.

PMID- 21941180
TI  - Immediate and early behavioral interventions for the prevention of acute and
      posttraumatic stress disorder.
AB  - PURPOSE OF REVIEW: The development of acute and posttraumatic stress symptoms
      after a traumatic event is common and often leads to personal distress,
      functional impairment, and economic consequences in trauma victims and their
      loved ones. Hence, the prevention of acute and chronic posttraumatic stress is an
      important public health priority. This article aims to review the current
      evidence regarding immediate (within hours) and early (within days and weeks)
      psychological and behavioral interventions to prevent posttraumatic stress
      symptoms. RECENT FINDINGS: Acute distress management, psychological debriefing
      and other immediate unspecific interventions within the first hours following a
      traumatic event have so far not demonstrated efficacy in preventing posttraumatic
      stress symptoms. So far, there are no randomized controlled trials (RCTs) that
      have examined immediate trauma-focused cognitive behavioral interventions. In
      contrast, some, but not many, studies have shown that cognitive behavioral
      interventions are efficacious if administered within days or weeks after a
      traumatic event. For other early interventions after trauma exposure, there is
      no, or only weak, evidence in support of their efficacy. However, conclusions are
      limited by the small numbers of trials examining immediate and early
      interventions. SUMMARY: Today, there is no empirical evidence to support any
      immediate intervention within hours after the traumatic event to prevent
      posttraumatic stress symptoms. With regard to early interventions in the first
      days or weeks after trauma, literature is also sparse, but supports brief
      cognitive behavioral interventions as a first choice. There is an urgent need for
      RCTs to examine if behavioral interventions immediately following a traumatic
      event might be able to reduce the burden of acute and posttraumatic stress
      symptoms.

PMID- 21941181
TI  - Repetitive transcranial magnetic stimulation in the treatment of auditory
      hallucinations in schizophrenic patients.
AB  - PURPOSE OF REVIEW: Since 1999, most studies have confirmed the initial positive
      results in the treatment of auditory verbal hallucination (AVH) with repetitive
      transcranial magnetic stimulation (rTMS) targeted to the classical site in the
      left temporo-parietal region. However, recent literature has tempered the initial
      interest in this treatment, requiring a new review on this topic. RECENT
      FINDINGS: From the four meta-analyses, the latest reported a moderate effect size
      of 0.54. Two recent controlled studies, not included in the meta-analyses, failed
      to observe a significant improvement of AVH after 1 Hz rTMS. While almost all
      trials have studied the effects of low-frequency rTMS (1Hz), two recent
      procedures using high-frequency (20 Hz) or continuous theta burst stimulation
      showed promising results. The interest in using cerebral imaging to increase the
      efficacy of rTMS in the treatment of AVH has not been clearly demonstrated.
      SUMMARY: Using rTMS to treat auditory hallucinations now seems less promising
      than it did 10 years ago because of the variable clinical effects and the high
      level of placebo responders. Evidence is still lacking concerning the maintenance
      treatment and the neurobiological underpinnings of rTMS efficacy, underscoring
      the need for further studies.

PMID- 21941183
TI  - Prolactin in men's health and disease.
AB  - PURPOSE OF REVIEW: To review physiology of prolactin (PRL), cause and managment
      of hyperprolactinemia, and discuss evolving diverse roles of PRL in men's health.
      RECENT FINDINGS: Hyperprolactinemia can be physiologically found after sexual
      activities, exercise, lactation, during pregnancy, and after stressful
      venipuncture. Elevated PRL can be caused by medications use, renal failure,
      hypothyroidism, and by prolactinoma - PRL secreting tumors. Symptomatic
      hyperprolactinemia and prolactinomas should be treated to lower PRL levels,
      decrease tumor size, and restore gonadal function. Three modes of treatment are
      typically utilized: pharmacological, radiosurgery with gamma radiation, and
      external beam radiation. Pharmacological treatment of prolactinomas is mainly
      based on dopamine agonists. The most frequently used dopamine agonists are
      bromocriptine and cabergoline. Cabergoline becoming the preferred drug in the
      treatment of prolactinomas because of higher response rate and less side-effects.
      Bromocriptine has been recently approved to improve glycemic control in diabetes
      mellitus. SUMMARY: PRL plays a diverse role in men's reproduction and health.
      Detecting and treating elevated PRL may not only improve infertility and
      hypogonadism but also have a positive effect on the metabolic profile of patient
      and control of glycemic control and metabolic profile - an important advantage
      considering dramatic and worldwide increase in obesity and diabetes.

PMID- 21941184
TI  - Reconstructive surgery.

PMID- 21941182
TI  - Male reproductive health and prostate cancer risk.
AB  - PURPOSE OF REVIEW: Male infertility impacts a substantial proportion of men and
      has serious implication for a man's quality of life. Advances in reproductive
      technology may allow men to bypass urologic care in order to achieve their family
      planning goals. Recent data suggests that male reproductive failure may be a
      harbinger of future urologic diseases, including prostate cancer (CaP), thus
      emphasizing the importance of dedicated urologic evaluation and care for all male
      infertility patients. RECENT FINDINGS: We will review the epidemiologic data that
      explores an association between male reproductive health and CaP. We will review
      the potential biologic mechanisms that may underlie this association, and explore
      possible reasons for inconsistencies in study findings. SUMMARY: Studies of the
      association between male infertility and CaP are inconsistent. Despite this, the
      association between reproductive health in a man's fourth decade (30s) and his
      development of aggressive CaP in his sixth decade (50s) should not be ignored.
      These findings, combined with the robustness of the potential common underlying
      mechanisms, provide a foundation for future studies of male reproductive health
      that are more specific in their approach to answering questions about the
      association between male reproductive failure and future systemic disease.

PMID- 21941185
TI  - Estrogens and phytoestrogens in male infertility.
AB  - PURPOSE OF REVIEW: A time-related negative trend in male reproductive function
      has been suggested. It has been hypothesized that this is due to exposure to
      chemicals interfering with the action of sex hormones. Also a negative effect of
      phytoestrogens on male fertility has been postulated. This review aimed to review
      the epidemiological evidence of deteriorating male reproductive function and
      summarize the most recent literature on exposure to endocrine disrupters and
      phytoestrogens in relation to male fertility and/or semen quality. RECENT
      FINDINGS: There is no doubt that the incidence of testicular cancer has increased
      through the past 50 years, a decline in sperm counts, if any, may have leveled
      off during the past decade. There are some reports indicating negative
      association between exposure to certain chemicals and sperm parameters such
      evidence has not been found for phytoestrogens. The majority of these studies
      have been limited to assessing postnatal exposure. SUMMARY: Although possible
      negative impact of industrial chemicals and male fertility is an important issue
      on the research agenda, so far, it has no clinical implications. The future
      research should focus on looking at the impact of low dose exposure to a mixture
      of chemicals, two generation studies and gene-environment interaction.

PMID- 21941186
TI  - Penile corporoplasty in Peyronie's disease:  which technique, which graft?
AB  - PURPOSE OF REVIEW: Despite continuous efforts to find an ideal solution, standard
      surgical technique for Peyronie's disease treatment is still not established. To
      evaluate the current articles and assess the scientific validity of the recent
      literature (January 2010-June 2011) on Peyronie's disease surgery. RECENT
      FINDINGS: Corporal surgery is coped with high complication rate because of
      complexity of penile anatomy and healing mostly in flaccid state. Penile
      structures are elastic with significant size change in erection, in contrary to
      rigid, nonelastic scarring tissue. This has important impact on surgical results,
      quality of life and patients' satisfaction. In the last 18 months, there were
      several articles that deserve our attention. Two articles evaluate medium and
      long-term results on corporal grafting. There are some newly described, minimally
      invasive approaches to albuginea, and some are describing new techniques for
      plaque attenuation. One study is dealing with selective calcified plaque excision
      and contralateral plication, and another describes different modalities of
      accurate tunical incision(s) and grafting for complete re-establishment of
      predisease penile size. SUMMARY: In the last 18 months, there are few works that
      could have impact for clinical practice, while one proved poor long-term results
      of dermal flap grafting.

PMID- 21941187
TI  - Safety of propofol in cirrhotic patients undergoing colonoscopy and endoscopic
      retrograde cholangiography:  results of a prospective controlled study.
AB  - BACKGROUND AND AIMS: Safety of propofol sedation in patients with liver cirrhosis
      undergoing colonoscopy or endoscopic retrograde cholangiopancreatography (ERCP)
      remains to be studied. The aim of this study was to investigate whether the use
      of propofol is safe for endoscopic procedures more complex than gastroscopy in
      patients with liver cirrhosis in a prospective controlled study. METHODS: Two
      hundred and fourteen consecutive patients, with or without cirrhosis, who
      underwent colonoscopy or ERCP with propofol sedation were recruited between
      January and June 2009. Administration of sedation was performed by
      anesthesiologists and outcome measures were recorded. Main outcomes were
      complication rates and recovery times. RESULTS: Sixty-one (28.5%) cirrhotic
      patients and 153 (71.5%) noncirrhotic patients were included. The incidence of
      sedation-related complications did not significantly differ between the two
      populations (11.5 vs. 17.0%, respectively, P=0.31). The mean (+/-SD) dose of
      propofol administered (213+/-86 vs. 239+/-100 mg, P=0.07), the mean time to
      achieve adequate sedation (3.3+/-1.1 vs. 3.0+/-1.2 min, P=0.21), the mean total
      duration of the endoscopic procedure (24.5+/-10.6 vs. 27.4+/-11.8 min, P=0.08),
      the mean time to reach Observer's Assessment of Alertness and Sedation Scale 5
      (17.2+/-4.4 vs. 18.4+/-5.6 min, P=0.15), the mean time from completion of the
      procedure to release (9.0+/-2.5 vs. 9.1+/-3.2 min, P=0.86), and the mean time to
      full recovery (42.2+/-7.3 vs. 42.3+/-7.8 min, P=0.88) were very similar between
      the two groups. The limitation of this study was lack of randomization, and a
      control group of cirrhotic patients using standard sedation with benzodiazepines
      and opioids. CONCLUSION: Propofol deep sedation administered by an
      anesthesiologist with appropriate monitorings seems to be a safe procedure during
      colonoscopy or ERCP in cirrhotic patients.

PMID- 21941188
TI  - A single center experience of sorafenib in advanced hepatocellular carcinoma
      patients:  evaluation of prognostic factors.
AB  - OBJECTIVE: Sorafenib is the only effective drug for advanced hepatocellular
      carcinoma (HCC), but few data predictive of its effectiveness are available. To
      address this issue we analyzed the relationship between risk factors associated
      with sorafenib treatment and overall survival (OS). METHODS: Forty patients with
      advanced HCC were treated with sorafenib. OS was the primary endpoint and tumor
      response was evaluated using the Response Evaluation Criteria in Solid Tumors.
      Demographics, and the efficacy and adverse effects of sorafenib were analyzed.
      Univariate and multivariate analysis were carried out to identify risk factors
      for OS. The side-effects of sorafenib were summarized, and published data related
      to sorafenib in patients with HCC were reviewed. RESULTS: The median OS was 12.7
      months. A partial response was achieved in five patients and stable disease was
      achieved in 24 patients, with a disease-stabilization rate of 60%. Hand-foot
      syndrome, hypertension, diarrhea, and fatigue were common adverse effects.
      Univariate analysis showed that tumor/lymph node/metastasis staging, Barcelona
      Clinic Liver Cancer staging, distant metastasis, ascites, and portal thrombosis
      were risk factors for OS. Multivariate analysis demonstrated that the presence of
      distant metastasis and ascites predicted poorer OS, and the presence of adverse
      effects predicted better OS. Presence of adverse effects can be used for
      monitoring the efficacy of sorafenib that has not been reported in previous
      studies. CONCLUSION: Sorafenib demonstrated good efficacy and acceptable
      tolerability in treating an advanced HCC patient population, with or without
      prior treatment. The presence of ascites or distant metastasis predicted poorer
      OS, and the presence of adverse effects predicted improved OS.

PMID- 21941189
TI  - Selective microcoil embolization of arterial gastrointestinal bleeding in the
      acute situation:  outcome, complications, and factors affecting treatment
      success.
AB  - OBJECTIVES: To evaluate microcoil embolization in the interventional treatment of
      acute upper and lower gastrointestinal bleeding. PATIENTS AND METHODS: Forty-four
      patients (29 men, 15 women) with active arterial gastrointestinal bleeding were
      treated with microcoil embolization. The analysis included technical/clinical
      success, morbidity, mortality, and intervention-related mortality. Age, sex,
      underlying malignant disease, number of embolizations, preinterventional and
      postinterventional hemoglobin levels, blood products administered peri
      interventionally, amount of embolization material used, duration of fluoroscopy,
      and use of contrast medium were evaluated for possible effects on technical and
      clinical success. RESULTS: The primary technical success rate of microcoil
      embolization for acute gastrointestinal bleeding was 88.6% with a clinical
      success rate of 56.8%. Minor and major complications occurred in 13.6 and 18.2%
      of patients, respectively. Intervention-associated mortality, due to intestinal
      ischemia, accounted for 4.6% of the total 18.2% mortality rate. Patients with
      technically successful embolization had a statistically significant increase in
      hemoglobin (P<0.01) after the intervention and a decrease in need for packed red
      blood cells, (P<0.01), fresh frozen plasma (P<0.01), and coagulation products
      (P<0.01). A smaller postinterventional fresh frozen plasma requirement was
      associated with a better clinical outcome (P=0.02). CONCLUSION: Microcoil
      embolization of arterial gastrointestinal bleeding in the acute situation has a
      high-technical success rate. The number of transfusions required before and after
      the intervention has no significant effect on technical success.
      Postinterventional fresh frozen plasma demand negatively correlates with clinical
      success.

PMID- 21941190
TI  - Determinants of patient's and doctor's delay in diagnosis and treatment of
      colorectal cancer.
AB  - BACKGROUND: Early detection and treatment is important for the management of
      colorectal cancer (CRC). AIM: To assess patient and doctor delay and their
      determinants. METHODS: A retrospective observational study in a primary care
      setting concerning 197 patients with CRC. The time between initial symptoms and
      the onset of treatment was categorized into four periods. With multivariable
      logistic regression analysis, determinants of delay were investigated. RESULTS:
      The median time from onset of symptoms until the start of treatment was 138 days.
      Median time for the four periods to: first general practitioner consult, first
      specialist consult, histological diagnosis, and start treatment were 30, 14, 27,
      and 18 days, respectively. Rectal blood loss and weight loss were significantly
      related to patient delay, whereas psychiatric comorbidity was related to delay in
      referral by the general practitioner. For delay in histological diagnosis and
      start of definitive treatment no determinants were found. Delay was not
      associated with more advanced disease stages. CONCLUSION: There is considerable
      delay in the management of CRC, especially in time to consultation and time to
      onset of clinical treatment. Education among the general public about the
      importance of alarm symptoms and increasing efficiency of the diagnostic process
      in hospital setting are a key in improving CRC disease management.

PMID- 21941191
TI  - Radiofrequency ablation for recurrent hepatocellular carcinoma in postresectional
      patients:  prognostic factors analysis.
AB  - BACKGROUND: Percutaneous ablation therapies can be used for recurrent
      hepatocellular carcinoma (HCC) in postresectional patients not eligible for
      repeat surgery. AIMS: To determine prognostic factors affecting the disease-free
      survival of postresectional patients after percutaneous ultrasound-guided
      radiofrequency ablation (RFA) for recurrent HCC. METHODS: From August 2003 to
      December 2009, patients who had received previous hepatectomy because of HCC and
      suffered from tumor recurrence were included. Among them, 82 patients who
      received initial percutaneous ultrasound-guided RFA were included. Various host,
      treatment, and therapeutic-related factors were analyzed. RESULTS: Eighty-two
      patients (64 men, mean age 64.27 years) were included. Sex (P=0.495), age
      (P=0.840), hepatitis marker (P=0.083), and Child-Pugh score (P=0.809) were not
      related to prognosis. Preresectional tumor number (P=0.502), recurrent tumor
      location (P=0.795), recurrent tumor number (P=0.533), pathology proved cirrhosis
      (P=0.889), and OKUDA stage of the primitive disease (P=0.865) were not related to
      prognosis, either. Survival rates were significantly related to the
      preresectional tumor size (P=0.008), microscopic portal vein invasion (P=0.001),
      recurrent tumor size (P<0.001), and preablation alpha-fetoprotein serum level
      (P=0.006). Ablation needle (P=0.373), ablation time (P=0.387), and postablation
      temperature (P=0.444) were not related to prognosis. Multivariate analysis
      revealed that microscopic portal vein invasion was the only factor that had a
      significant effect on patient survival. CONCLUSION: In patients with
      postresectional HCC treated with percutaneous ultrasound-guided RFA for recurrent
      disease, those without microscopic portal vein invasion had a significantly
      higher probability of disease-free survival.

PMID- 21941192
TI  - Host risk factors and autochthonous hepatitis E infection.
AB  - INTRODUCTION: In developed countries autochthonous hepatitis E infection is
      caused by hepatitis E virus (HEV) genotype 3 or 4 and mainly affects middle
      aged/elderly men. Host factors might explain why older men develop clinically
      overt disease. METHODS: Retrospective review of 53 patients with symptomatic
      autochthonous hepatitis E infection to determine putative host risk factors.
      Patients were compared with 564 controls with adjustment for age and sex. Anti
      HEV seroprevalence was determined in controls and 189 patients with chronic liver
      disease. RESULTS: Mean age of the patients was 62.4 years, 73.6% were men.
      Compared with controls, patients with hepatitis E were more likely to drink at
      least 22 U alcohol/week (OR=9.4; 95% confidence interval=3.8-25.0; P<0.001). The
      seroprevalence of anti-HEV IgG in controls increased with age (P<0.001) but was
      similar in men and women. There was no association between alcohol consumption
      and anti-HEV IgG seroprevalence in the control group. There was no difference in
      the anti-HEV IgG seroprevalence between the controls and patients with chronic
      liver disease of all aetiologies, but seroprevalence was higher in controls
      (13.8%) than patients with alcoholic liver disease (4.8%, P=0.04). CONCLUSION:
      Clinically apparent hepatitis E infection is more common in individuals who
      consume at least 22 U alcohol/week. Patients with established chronic alcoholic
      liver disease have a low seroprevalence compared with controls. The reason for
      this observation is uncertain, but patients with alcoholic liver disease have
      clinically severe disease with a high mortality when exposed to HEV. The low
      seroprevalence in this group may represent a 'culled' population.

PMID- 21941193
TI  - Hepatosplenic T-cell lymphoma in patients receiving TNF-alpha inhibitor therapy: 
      expanding the groups at risk.
AB  - BACKGROUND: Hepatosplenic T-cell lymphoma (HSTCL) is a rare, lethal disease
      generally seen in young male patients with inflammatory bowel disease. The study
      of biologic and immunomodulator naive patients in Crohn's disease (SONIC),
      advocates combining infliximab with an immunomodulator in moderate-to-severe
      Crohn's disease. Unfortunately, combined immunosuppression increases risk for
      HSTCL. We herein review all cases of HSTCL reported to the Food and Drug
      Administration (FDA) in patients receiving TNF-alpha inhibitors. METHODS:
      Individual reports from the FDA Adverse Event Reporting System database for
      lymphomas from the biological agents - infliximab, adalimumab, certolizumab,
      natalizumab, and etanercept were downloaded and analyzed with Microsoft Access.
      Full reports for all identified HSTCL cases were obtained from the FDA. RESULTS:
      Twenty-five cases of HSTCL were identified. Twenty-two (88%) patients had
      inflammatory bowel disease and three had rheumatoid arthritis. Four cases (16%)
      were in women and four patients were above 65 years of age. Twenty-four cases
      (96%) also received an immunomodulator (azathioprine, 6-mercaptopurine, or
      methotrexate). Two patients received adalimumab alone. CONCLUSION: HSTCL is no
      longer restricted to the previously identified risk group of young male patients,
      but can also occur in patients with rheumatoid arthritis, females and older
      adults receiving TNF-alpha inhibitors and immunomodulators. Improved disease
      outcomes using combination therapy should be tempered by the risk of developing
      HSTCL.

PMID- 21941194
TI  - Predictive value of bronchoscopy in assessing the severity of inhalation injury.
AB  - Inhalation injury is associated with severe pulmonary complications as inhaled
      products of combustion cause lung inflammation and loss of natural defenses. A
      bronchoscopic grading for inhalation injury has been proposed but has not yet
      been validated in burn patients. In this study, the authors evaluated whether
      bronchoscopic grading of injury clinically correlated with indices of gas
      exchange over the first 72 hours or predicted differences in hospitalization
      outcomes. They conducted a single-center retrospective review of all mechanically
      ventilated adults with suspected inhalation injury and thermal injury over an 18
      month period. All recorded bronchoscopy examinations were reviewed and
      categorized injury according to the published abbreviated injury score (AIS 0: no
      injury, 1: mild, 2: moderate, 3: severe, and 4: massive injury). They also
      compared changes in oxygenation, airway pressures, chest radiograph findings,
      fluid administration, and early development of pneumonia and organ failure, by
      severity of inhalation injury according to the AIS. Thirty-two adult patients met
      inclusion criteria over the study period. This cohort was 69% male with a mean
      age of 44.5 +/- 14 years and a mean % TBSA burn of 33.9 +/- 17%. Of these 32
      patients, 11 patients (34%) were classified as grade 0, 9 patients (28%) were
      classified as grade 1, 7 patients (22%) were classified as grade 2, and 5
      patients (16%) were classified as grade 3. Measured carboxyhemoglobin levels
      increased significantly with higher AIS grade. Oxygenation indices were worse as
      grade worsened by 24, 48, and 72 hours. The incidence of acute respiratory
      distress syndrome increased by grade of injury: 0, 22, 57, and 80%, respectively,
      at 24 hours (P < .01), and remained statistically different at 48 and 72 hours.
      After adjustment for age, % TBSA burn, and full-thickness component, severe
      inhalation injury (grades 2 and 3) was associated with an increased risk of acute
      respiratory distress syndrome at 24 and 72 hours, as well as ventilator days >21
      days, and a trend toward multiple organ dysfunction syndrome and mortality.
      Better understanding of the relationship between inhalation injury and lung
      physiologic sequelae is a burn research priority. The bronchoscopic grading of
      inhalation injury moderately correlates with early indices of impaired gas
      exchange in this cohort and may be a promising tool for staging lower airway
      injury. Prospective studies should definitively answer whether AIS bronchoscopy
      staging predicts hospitalization outcomes in inhalation injury.

PMID- 21941195
TI  - Outcomes and predictors in burn rehabilitation.
AB  - Advances in burn care in recent decades have resulted in a growing population of
      burn survivors and an increased need for inpatient rehabilitation. Burn survivors
      who require inpatient rehabilitation typically experience severe and complicated
      injuries. The purpose of this study is to examine burn rehabilitation outcomes
      and their predictor variables. Data are obtained from the Uniform Data System for
      Medical Rehabilitation from 2002 to 2007. Inclusion criterion is primary
      diagnosis of burn injury. Predictor variables include demographic, medical, and
      facility data. Outcome measures are length of stay efficiency, FIM(r) gain,
      community discharge, and FIM(r) discharge of at least 78. Linear and logistic
      regression analyses are used to determine significant predictors of outcomes.
      There are 2920 patients who meet inclusion criteria. The mean age of the
      population is 51 years, 33% of the population is female, 73% is Caucasian, and
      40% are married. The median TBSA decile is 20 to 29%. The population exhibits a
      mean FIM(r) gain of 28 and length of stay efficiency of 2.1. A majority of the
      population is discharged to the community (76%) and has a FIM(r) discharge of at
      least 78 (81%). Significant predictors of outcomes in burn rehabilitation include
      age, FIM(r) admission, onset days, employment status, and marital status.
      Inpatient rehabilitation is critical to community reintegration of burn
      survivors. Survivors who are young, married, employed, and higher functioning at
      the time of admission to rehabilitation demonstrate the best outcomes. This
      research will help assess the rehabilitation potential of burn survivors and
      inform resource allocation.

PMID- 21941196
TI  - Comparison of invasive and non-invasive measurements of haemodynamic parameters
      in patients with advanced heart failure.
AB  - AIM: Measurement of haemodynamic parameters using a Swan-Ganz catheter is of
      clinical importance in patients with advanced heart failure; however, its
      applicability is limited due to its invasiveness. The aim of the study was to
      estimate the concordance between invasive and non-invasive measurements of
      haemodynamic parameters in patients with advanced heart failure. METHODS AND
      RESULTS: We examined 25 patients with advanced heart failure (20 men, age: 64 +/-
      11 years, New York Heart Association class III/IV: 88/12%, left ventricular
      ejection fraction: 37 +/- 20%), 13 (52%) demonstrated decompensated heart
      failure. Resting haemodynamic parameters were measured simultaneously using two
      methods: an invasive Swan-Ganz catheterization and a thermodilution technique;
      and a non-invasive recording using a device for finger arterial pressure waveform
      analysis. The following parameters were analysed: stroke volume (SV, ml), cardiac
      output (CO, l/min) and systemic vascular resistance (SVR, dyne * s/cm5). The
      concordance between these two methods was assessed using the variability
      coefficient calculated according to a Bland-Altman method. Comparing the invasive
      and non-invasive measures, variability coefficients were: 13, 18 and 11% for SV,
      SVR and CO, respectively. Similar variability coefficients were obtained when
      invasive and non-invasive measurements were compared in prespecified subgroups of
      patients, distinguished based on the presence of decompensation, atrial
      fibrillation and values of SBP. CONCLUSIONS: Evaluation of haemodynamic
      parameters using a non-invasive method based on a pressure pulse contour model
      reveals an adequate concordance with the measures obtained using an invasive
      approach. Our results suggest that a non-invasive method for haemodynamic
      monitoring could be applied in clinical practice in patients with advanced heart
      failure.

PMID- 21941197
TI  - Successful medical management of a huge left main thrombus with bilateral
      coronary embolization.
AB  - We report the case of a patient with a huge nonocclusive left main thrombus
      without underlying angiographic coronary lesion associated with bilateral
      coronary embolization, which was successfully and exclusively medically treated.

PMID- 21941198
TI  - Coexistence of idiopathic left ventricular aneurysm and aneurysm of right
      coronary artery.
AB  - A 40-year-old man was admitted to our hospital with dyspnea and atypical chest
      pain. Left ventricle (LV) apico-lateral wall aneurysm and right coronary artery
      aneurysm were found. We could find no etiological reason for this condition.
      Surgical treatment was considered but the patient refused. In this report, we
      describe an interesting and rare case of idiopathic LV aneurysm accompanied by
      coronary artery aneurysm.

PMID- 21941199
TI  - Collateral coronary circulation in acute coronary syndrome:  sometimes it's
      enough, sometimes it's not!
AB  - A young patient experienced two subsequent acute coronary syndromes due to left
      anterior descending (LAD) artery occlusion. Different ability of homocoronary
      collateral vessels to supply the ischemic territories, depending on the site of
      LAD artery occlusion, was associated with different clinical consequences. The
      case underscores the crucial role of the collateral circulation in limiting the
      effects of acute coronary occlusions.

PMID- 21941200
TI  - Delaying cardioversion following 4-week anticoagulation in case of persistent
      atrial fibrillation after a transcatheter ablation procedure to reduce silent
      cerebral thromboembolism:  a single-center pilot study.
AB  - BACKGROUND: Symptomatic cerebral thromboembolism occurs in 0.4% of transcatheter
      atrial fibrillation ablation procedures. Silent cerebral events, instead, have
      recently been reported in up to 14%, especially clustered within patients
      undergoing cardioversion at the end of the procedure. The present study reports
      the incidence of silent cerebral thromboembolism, assessed by cerebral MRI,
      delaying electrical cardioversion, in case of lack of sinus rhythm restoration at
      the end of the procedure, after 4 weeks of effective anticoagulation. METHODS AND
      RESULTS: Ninety-five consecutive patients with antiarrhythmic drug refractory
      atrial fibrillation were referred for transcatheter ablation and enrolled in the
      study. All patients underwent pre-ablation and post-ablation cerebral MRI.
      Overall, post-ablation cerebral MRI registered new thromboembolism in six (6%)
      patients. Fifty-five (58%) patients remained in sinus rhythm throughout the
      procedure and 40 (42%) reported persistent atrial fibrillation, yielding a silent
      thromboembolism incidence of 5 and 8%, respectively. In particular, silent
      thromboembolism was registered in one (4%) of the 25 patients achieving sinus
      rhythm by catheters, in two (18%) of the 11 patients spontaneously restoring
      sinus rhythm shortly following the procedure and in none of the four patients
      cardioverted following 4-week anticoagulation. In a matched reference population,
      a significantly higher percentage of patients (15, 16% vs. 6, 6%; P = 0.03)
      suffered from a new post-ablation thromboembolism; particularly within patients
      terminating the procedure in atrial fibrillation. Delaying cardioversion reduced
      silent cerebral thromboembolism from 38 to 13%. CONCLUSION: Delaying electrical
      cardioversion after a 4-week anticoagulation period reduced the risk of silent
      cerebral thromboembolism and is a viable and safer option in patients terminating
      a transcatheter ablation procedure in atrial fibrillation.

PMID- 21941201
TI  - A big floating thrombus in the common carotid artery.
AB  - The management of the free-floating thrombus (FFT) is difficult, and it is
      unclear whether surgical or medical treatment is superior. The common carotid
      artery is rarely involved. An 80-year-old woman presented with right hand
      weakness and syncope. Ultrasound showed the presence of FFT in the left common
      carotid artery. A carotid endarterectomy with Dacron patch angioplasty was
      immediately performed without complications. In the presence of symptoms, the
      interventional management of FFT is advised.

PMID- 21941202
TI  - Effect of primary percutaneous coronary intervention on myocardial
      repolarization.
AB  - OBJECTIVE: We aimed to investigate the effect of coronary perfusion on QT
      interval dispersion in patients with acute myocardial infarction (MI). METHODS:
      Seventy-seven consecutive patients who had undergone primary percutaneous
      coronary intervention (PCI) for a first ST segment elevation MI during the first
      12 h of symptom onset were included in the study. After achievement of
      thrombolysis in MI (TIMI) 3 flow of the infarct-related artery, corrected TIMI
      frame count (cTFC) and TIMI myocardial perfusion grade (TMPG) were measured. ECGs
      were performed in the following manner: at baseline, within 1 h after completion
      of the procedure, 24 h after the procedure and 48 h after the procedure. The
      corrected QT dispersion (QTd) and ST segment resolution (STR) were calculated.
      RESULTS: There was a difference between the durations of corrected QTd (cQTd)
      before PCI and cQTd just after PCI. On the first day, cQTd before PCI was
      significantly more prolonged (52.3 +/- 80 vs. 41.5 +/- 49, P = 0.05) than cQTd on
      second day (52.3 +/- 80 vs. 37 +/- 50, P = 0.001). In the correlation analysis
      conducted among the durations of cQTd, cTFC and TMPG, no significant association
      was established. STR was, however, inversely correlated with duration of cQTd.
      CONCLUSION: Our study results demonstrated that primary percutaneous coronary
      intervention leads to progressive shortening of QT dispersion in successful
      reperfusion, even in reduced cTFC.

PMID- 21941203
TI  - Predictive value of fragmented QRS in primary prevention implantable cardioverter
      defibrillator recipients with left ventricular dysfunction.
AB  - INTRODUCTION: In primary prevention implantable cardioverter defibrillator (ICD)
      patients, the incidence of appropriate ICD therapy is relatively low, prompting
      better risk stratification. Fragmented QRS (fQRS) on a 12-lead ECG has been
      associated with adverse outcomes. The aim of this study was to evaluate the
      prognostic value of fQRS in ICD recipients. METHODS: Consecutive ICD patients
      implanted at our institution for primary prevention of sudden cardiac death (SCD)
      were retrospectively evaluated. Patients were divided in two groups based on the
      presence or the absence of fQRS on the ECG obtained before ICD implantation. The
      endpoint of the study was all-cause mortality or the occurrence of any
      appropriate ICD-delivered therapy, whether shock or antitachycardia pacing.
      RESULTS: Among 394 ICD recipients (334 men, age 66.4  +/-  11.0), fQRS was
      observed in 103 patients (26.1%). There were 189 patients (48.0%) with wide QRS
      at the time of implantation. Among these patients, fQRS was found in 29
      individuals (28.2%). Patients in fQRS(+) group were more likely to have coronary
      artery disease and a lower QRS duration than those without fQRS. During a mean
      follow-up of 26.3  +/-  17.5 months, mortality or ICD therapy were 19.4 and
      22.4%, respectively, for fQRS(+) patients, and 15.2 and 22.8% for fQRS(-)
      patients (P = NS). By Kaplan-Meier analysis, event-free survival was similar in
      the two groups. CONCLUSION: In ICD recipients for primary prevention of SCD, fQRS
      is not helpful in selecting a subgroup of patients who benefit from prophylactic
      ICD implantation.

PMID- 21941204
TI  - Urinary renin, but not angiotensinogen or aldosterone, reflects the renal renin
      angiotensin-aldosterone system activity and the efficacy of renin-angiotensin
      aldosterone system blockade in the kidney.
AB  - OBJECTIVE: To study which renin-angiotensin-aldosterone system (RAAS) component
      best reflects renal RAAS activity. METHODS AND RESULTS: We measured urinary and
      plasma renin, prorenin, angiotensinogen, aldosterone, albumin and creatinine in
      101 diabetic and nondiabetic patients with or without hypertension. Plasma
      prorenin was elevated in diabetic patients. Urinary prorenin was undetectable.
      Urinary albumin and renin were higher in diabetic patients. Men had higher plasma
      renin/prorenin levels, and lower plasma angiotensinogen levels than women. Plasma
      creatinine and albumin were also higher in men. Urinary RAAS components showed no
      sexual dimorphism, whereas urinary creatinine and albumin were higher in men.
      Angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor
      blockers increased plasma renin and decreased plasma angiotensinogen, without
      altering plasma aldosterone. In contrast, in urine, these drugs decreased renin
      and aldosterone without affecting angiotensinogen. When analyzing all patients
      together, urinary angiotensinogen excretion closely mimicked that of albumin,
      whereas urinary angiotensinogen and albumin levels both were 0.05% or less of
      their concomitant plasma levels. This may reflect the identical glomerular
      filtration and tubular handling of both proteins, which have a comparable
      molecular weight. In contrast, urinary renin excretion did not correlate with
      urinary albumin excretion, and the urinary/plasma concentration ratio of renin
      was more than 200 times the ratio of albumin, despite its comparable molecular
      weight. Urinary aldosterone excretion closely followed urinary creatinine
      excretion. CONCLUSION: The increased urinary renin levels in diabetes and the
      decreased urinary renin levels following RAAS blockade, occurring independently
      of changes in plasma renin, reflect the activated renal RAAS in diabetes and the
      success of RAAS blockade in the kidney, respectively. Urinary renin, therefore,
      more closely reflects renal RAAS activity than urinary angiotensinogen or
      aldosterone.

PMID- 21941205
TI  - Association of plasma renin activity and aldosterone-renin ratio with prevalence
      of chronic kidney disease:  the Kaiser Permanente Southern California cohort.
AB  - BACKGROUND: Although higher plasma renin activity (PRA) is associated with poor
      clinical outcomes including higher death and cardiovascular events, its
      association with prevalence of chronic kidney disease (CKD) is not clear. We
      hypothesized that higher levels of PRA and lower levels of aldosterone-to-PRA
      ratios (ARRs) are associated with greater CKD prevalence in a large and
      ethnically diverse population of southern California who underwent uniform
      healthcare. METHODS: During the period 1 January 1998 to 31 October 2009, the
      adult population who was under the care of Kaiser Permanente Southern California
      with documented outpatient values of PRA and minimum of 6 months continuous
      enrollment were examined. CKD defined by an estimated glomerular filtration rate
      (eGFR) less than 60 ml/min per 1.73 m2. PRA levels and ARR were categorized into
      quartiles. Multivariate logistic regressions were used to calculate odds ratios
      for CKD based on PRA controlling for age, sex, black race, diabetes status,
      hypertension, and type of medication use. RESULTS: We identified 9495 individuals
      including 7887 with hypertension. Study population included 60% women, 35%
      whites, 20% blacks, 20% Hispanics, and 26% diabetic patients. Adjusted odds
      ratios (95% confidence interval) for CKD across second, third, and fourth
      quartiles of PRA quartile (reference: first quartile) were 1.5 (1.2-1.7), 1.5
      (1.3-1.8), and 2.2 (1.9-2.6), respectively. Each 10-unit increase in PRA was
      associated with odds ratio for CKD of 1.3 (1.2-1.4). ARR showed a similar but
      inverse trend with CKD. CONCLUSION: Higher levels of PRA are associated with
      greater rates of CKD in our large ethnically diverse population of primarily
      hypertensive patients. Whether modulation of PRA can mitigate prevalence of CKD
      needs to be studied in interventional trials.

PMID- 21941206
TI  - Blood pressure class and carotid artery intima-media thickness in a population at
      the secondary epidemiological transition.
AB  - OBJECTIVES: Data relating blood pressure (BP) class to subclinical organ damage
      are infrequently reported in populations with a traditional 'nonwestern'
      lifestyle. As the relevance of BP stratification to cardiovascular prognosis has
      not been elucidated in these low-income countries at the second epidemiological
      transition, we aimed to study the effect of BP class on carotid artery intima
      media thickness (IMT) in Flores Island, Indonesia. METHODS: A cross-sectional
      study was performed in 476 inhabitants (men/women) of Flores. BP was classified
      using the European Society of Hypertension/European Society of Cardiology
      classification. The primary endpoint was mean carotid-IMT measured by
      ultrasonography in classes of BP. Covariate analysis was performed adjusting for
      conventional cardiovascular risk factors. RESULTS: BP ranged from 94 to 250 mmHg
      systolic and 50 to 125 mmHg diastolic, 35% of the population had 'grade-I
      hypertension' or higher, 1.7% of the population was short-term treated with
      antihypertensive therapy. IMT significantly differed for BP classes (P < 0.001).
      Mean (+/- SEM) IMT was 587.8 (+/- 9.3) MUm, 621.5 (+/- 7.6) MUm, 653.6 (+/- 10.5)
      MUm, 717.9 (+/- 14.0) MUm, and 750.1 (+/- 21.8) MUm for 'optimal', '(high)
      normal', 'grade-I, grade-II, and grade-III hypertension' classes, respectively.
      After adjustment for cardiovascular risk factors, similar results were obtained.
      CONCLUSION: A strong association was found between BP class and carotid artery
      IMT in treatment-naive participants of a population with a traditional lifestyle,
      at the second epidemiological transition. Intriguingly, the increase of IMT was
      already observed at the 'high normal' BP class. This study may help to prioritize
      preventive and therapeutic measures to lower BP in countries at the second
      epidemiological transition.

PMID- 21941207
TI  - Renin-angiotensin and sympathetic nervous system contribution to high blood
      pressure in Schlager mice.
AB  - OBJECTIVE: Schlager hypertensive (BPH/2J) mice have been suggested to have high
      blood pressure (BP) due to an overactive sympathetic nervous system (SNS), but
      the contribution of the renin-angiotensin system (RAS) is unclear. In the present
      study, we examined the cardiovascular effects of chronically blocking the RAS in
      BPH/2J mice. METHODS: Schlager normotensive (BPN/3J, n = 6) and BPH/2J mice (n =
      8) received the angiotensin AT 1A-receptor antagonist losartan (150 mg/kg per
      day) in drinking water for 2 weeks. Pre-implanted telemetry devices were used to
      record mean arterial pressure (MAP), heart rate (HR) and locomotor activity.
      RESULTS: MAP was reduced by losartan treatment in BPN/3J (-23 mmHg, P < 0.01) and
      in BPH/2J mice (-25 mmHg, P < 0.001), whereas HR was increased. Losartan had
      little effect on initial pressor responses to feeding or to stress, but did
      attenuate the sustained pressor response to cage-switch stress. During the active
      period, the hypotension to sympathetic blockade with pentolinium was greater in
      BPH/2J than BPN/3J (suggesting neurogenic hypertension), but was not affected by
      losartan. During the inactive period, a greater depressor response to pentolinium
      was observed in losartan-treated animals. CONCLUSION: The hypotensive actions of
      losartan suggest that although the RAS provides an important contribution to BP,
      it contributes little, if at all, to the hypertension-induced or the greater
      stress-induced pressor responses in Schlager mice. The effects of pentolinium
      suggest that the SNS is mainly responsible for hypertension in BPH/2J mice.
      However, the RAS inhibits sympathetic vasomotor tone during inactivity and
      prolongs sympathetic activation during periods of adverse stress, indicating an
      important sympatho-modulatory role.

PMID- 21941208
TI  - Sympathetic nerve hyperactivity and its effect in postmenopausal women.
AB  - OBJECTIVES: Hypertension and its subsequent cardiovascular complications have
      been associated with sympathetic neural activation, and their prevalence in women
      increases after the menopause. However, there have been no data on the level of
      sympathetic activation and its relationship to vascular blood flow following the
      menopause. Therefore, we planned to find out whether the behavior of muscle
      sympathetic nerve activity (MSNA) and calf blood flow (CBF) in women with and
      without essential hypertension (EHT) is changed following the menopause. METHODS:
      Peroneal nerve activity was measured as mean frequency of single units and of
      multiunit bursts with simultaneously measured CBF in two matched groups of
      postmenopausal women with and without EHT in comparison with two matched groups
      of premenopausal women with and without EHT. RESULTS: As expected, nerve activity
      was greater in the hypertensive than in normotensive groups and in postmenopausal
      than in premenopausal normotensive groups. We found that single unit frequency in
      postmenopausal hypertensives (65 +/- 3.9 impulses/100 cardiac beats) was not
      significantly different from that in postmenopausal normotensives (54 +/- 2.2
      impulses/100 cardiac beats) or in premenopausal hypertensives (57 +/- 2.8
      impulses/100 cardiac beats). Similar results were obtained for burst frequency.
      In addition, a statistically significant negative correlation between the
      frequency of nerve activity and CBF was found only in postmenopausal normotensive
      (at least r =  -0.42, P < 0.04) and hypertensive women (at least r =  -0.45, P <
      0.03). CONCLUSION: These findings suggest that sympathetic nerve hyperactivity in
      postmenopausal women may have greater vascular effects than in premenopausal
      women, and could have implications in the management of EHT in postmenopausal
      women.

PMID- 21941209
TI  - Mechanism of action of vitamin D in the asthmatic lung.
AB  - Vitamin D, or 1,25-dihydroxy vitamin D (1,25[OH]D), in its activated form, has
      long been recognized as a critical mediator in bone health. New research has
      identified 1,25(OH)D as also vital for respiratory health. Owing to its intrinsic
      anti-inflammatory properties, 1,25(OH)D may be very important in people with
      asthma. This review article seeks to evaluate the current literature to delineate
      the potential mechanisms of action by which 1,25(OH)D affects asthma. We
      summarize the evidence that 1,25(OH)D has receptors in multiple lung cell types
      and acts to abrogate asthma by several mechanisms: promoting lung immunity,
      decreasing inflammation, slowing cell cycling, reducing hyperplasia, and
      enhancing the effects of exogenous steroids. Put together, there is compelling
      evidence for the role of vitamin D in asthma.

PMID- 21941210
TI  - Acute kidney injury and chronic kidney disease in hospitalized patients with
      cirrhosis.
AB  - BACKGROUND: Renal dysfunction is a common and potentially life-threatening
      complication in hospitalized patients with cirrhosis. AIMS: To determine the
      prevalence, cause, and outcome of patients with cirrhosis and acute kidney injury
      (AKI) and/or chronic kidney disease (CKD). METHODS: This retrospective analysis
      examined hospital records of 152 consecutive patients with cirrhosis and
      creatinine levels of 1.5 mg/dL or greater. Multiple clinical and laboratory
      variables were abstracted for each subject. Precise definitions were used to
      define cirrhosis and etiologies of renal dysfunction. Univariate and
      multivariable logistic regression analyses were performed to identify features
      with prognostic value for hospital mortality. RESULTS: The most common type of
      renal dysfunction was AKI, present in 107 patients (70%). Acute kidney injury
      plus CKD was found in 26 patients (17%), and CKD alone was present in 19 patients
      (13%). Prerenal azotemia was the most common cause of AKI (69%), often occurring
      secondary to gastrointestinal hemorrhage. The overall mortality for the cohort
      was 31%, with the highest mortality occurring in patients with type 1 hepatorenal
      syndrome (HRS) (11/14, 79%). We were unable to identify any patient meeting
      diagnostic criteria for type 2 HRS. The development of AKI on preexisting CKD did
      not infer worse prognosis than AKI alone. The presence of upper gastrointestinal
      bleeding, bacteremia, and HRS-1 predicted mortality. CONCLUSIONS: Both AKI and
      CKD are common in hospitalized patients with cirrhosis, often occurring
      simultaneously. Type 2 HRS was not identified, suggesting that its diagnostic
      criteria may need reevaluation or that this syndrome may not represent a unique
      functional kidney disorder.

PMID- 21941211
TI  - Levels of soluble advanced glycation end product-receptors and other soluble
      serum markers as indicators of diabetic neuropathy in the foot.
AB  - OBJECTIVE: Advanced glycation end products (AGEs) and the interaction with their
      receptors (RAGE) play an important role in the pathogenesis of diabetic foot (DF)
      associated with diabetic neuropathy. Our study examined the association between
      asymmetric dimethyl arginine (ADMA), fructosamine, nitric oxide (NO), and soluble
      (s) RAGE levels in serum of diabetic patients with and without neuropathy.
      METHODS: Circulating levels of ADMA, fructosamine, NO, and sRAGE, estimated
      either chemically or by enzyme-linked immunosorbent assay, were examined in 60
      type 2 diabetes mellitus (T2DM) overweight/obese (body mass index, 30.5 +/- 1.5
      kg/m2) male patients and 20 age-matched (55 +/- 3 years) obese healthy subjects
      as control group. The T2DM subjects were categorized as patients without DF (n =
      30), and the remaining were patients with DF associated with neuropathy. RESULTS:
      First sRAGE levels were significantly increased in T2DM patients without DF in
      comparison to healthy controls (1656.6 [1198.8-2065.4] vs 1111.7 [909-1605.3]
      pg/mL, respectively; P < 0.05). However, in the DF group (1049.6 [783.7-1221.8]
      pg/mL), its level decreased significantly in comparison to both groups (P <
      0.05). However, ADMA and fructosamine were significantly higher in diabetic
      patients with DF than both T2DM without DF and healthy controls. Moreover, NO was
      significantly lower in DF than in diabetic patients without DF and controls (5 +/
      0.4 and 8 +/- 0.4 vs 42 +/- 2.5 MUmol/L, respectively; P < 0.05). Finally, sRAGE
      levels were significantly correlated with ADMA, fructosamine, and NO.
      CONCLUSIONS: Soluble forms of the receptor for advanced glycation end product
      could be an endogenous protection factor against occurrence of DF, hence may be
      of therapeutic value in the treatment of DF.

PMID- 21941212
TI  - Implementation and impact of a consensus diagnostic and management algorithm for
      complicated pneumonia in children.
AB  - INTRODUCTION: Variable treatment exists for children with bacterial pneumonia
      complications such as pleural effusion and empyema. Subspecialists at an urban
      academic tertiary children's hospital created a literature-based diagnosis and
      management algorithm for complicated pneumonia in children. We proposed that
      algorithm implementation would reduce use of computed tomography (CT) for
      diagnosis of pleural infection, thereby decreasing radiation exposure, without
      increased adverse outcomes. MATERIALS AND METHODS: A cross-sectional study was
      undertaken in children (3 months to 20 years old) with principal or secondary
      diagnosis codes for empyema and/or pleural effusion in conjunction with bacterial
      pneumonia. Study cohorts consisted of subjects admitted 15 months before (cohort
      1, n = 83) and after (cohort 2, n = 87) algorithm implementation. Data were
      collected using clinical and financial data systems. Imaging studies and
      procedures were identified using Current Procedural Terminology codes.
      Statistical analysis included chi test, linear and ordinal regression, and
      analysis of variance. RESULTS: Age (P = 0.56), sex (P = 0.30), diagnoses (P =
      0.12), and severity level (P = 0.84) were similar between cohorts. There was a
      significant decrease in CT use in cohort 2 (cohort 1, 60% vs cohort 2, 17.2%; P =
      0.001) and reduction in readmission rate (7.7% vs 0%; P = 0.01) and video
      assisted thoracoscopic surgery procedures (44.6% vs 28.7; P = 0.03), without
      concomitant increases in vancomycin use (34.9% vs 34.5%; P = 0.95) or hospital
      length of stay (6.4 vs 7.6 days; P = 0.4). Among patients who received video
      assisted thoracoscopic surgery drainage (n = 57), there were no significant
      differences between cohorts in median time from admission to video-assisted
      thoracoscopic surgery (2 days; P = 0.29) or median duration of chest tube
      drainage (3 vs 4 days; P = 0.10). There was a statistically nonsignificant trend
      for higher rate of pathogen identification in cohort 2 (cohort 1, 33% vs cohort
      2, 54.1%; P = 0.12); Streptococcus pneumonia was the most commonly identified
      pathogen in both cohorts (37.5% vs 27%; P = 0.23). DISCUSSION: Implementation of
      an institutional complicated pneumonia management algorithm reduced CT scan
      use/radiation exposure, VATS procedures, and readmission rate in children with a
      diagnosis of pleural infection, without associated increases in length of stay or
      vancomycin use. This algorithm provides the framework for future prospective
      quality improvement studies in pediatric patients with complicated pneumonia.

PMID- 21941213
TI  - The evaluation of hypoxia-inducible factor 1 in N-nitro-L-arginine methyl ester
      preeclampsia model of pregnant rats.
AB  - OBJECTIVE: The objective of the study was to evaluate hypoxia-inducible factor 1
      (HIF-1), which plays a major role in the stimulation of angiogenesis in placental
      tissues, by using immunohistochemical staining in preeclampsia model of rats,
      developed by N-nitro-L-arginine methyl ester (L-NAME) METHODS: Thirty pregnant
      rats were randomized into 2 groups (n = 15 in each group) on day 10 of gestation.
      L-NAME was given to rats in the study group by gavage. On days 0, 10, and 20 of
      gestation, rats were weighted, and urine protein values and blood pressures were
      measured. Hypoxia-inducible factor 1 expressions were assessed with
      immunohistochemical staining by using avidin-biotin peroxidase via selecting
      preparation. RESULTS: Systolic and diastolic blood pressures and urine protein
      value of L-NAME group on day 20 of gestation were found to be significantly
      higher than those obtained on days 0 and 10 of gestation in the same group and
      those obtained on day 20 of gestation in the sham group (P < 0.05). Maternal
      weight, number of fetuses, and mean fetal weight of rats in L-NAME group on day
      20 of gestation were found to be significantly lower than those obtained from
      rats in the sham group (P < 0.05). Regarding HIF-1 expression of placental
      tissues, mild immunohistochemical staining was found in 2 rats (13.4%) and
      moderate in 13 rats (86.6%) in the L-NAME group. A significant difference was
      found in terms of HIF-1 positivity in the maternal placentas of both groups (P <
      0.05). CONCLUSIONS: L-NAME preeclampsia model of pregnant rats is consistent with
      human preeclampsia in terms of hypertension, proteinuria, and intrauterine growth
      retardation; in addition, it also shows evidence of placental hypoxia findings.

PMID- 21941214
TI  - Cat scratch neuroretinitis:  the role of acute and convalescent titers for
      diagnosis.
AB  - Cat scratch neuroretinitis (CSN) is a clinical diagnosis supported by serological
      testing. We present 2 cases of CSN in which initial acute titers were negative or
      equivocal for Bartonella henselae while convalescent titers were shown to be
      positive. We report these cases to emphasize that a single acute negative titer
      is insufficient to exclude the diagnosis of CSN and that convalescent titers
      should be obtained in patients for whom there is a high clinical suspicion of the
      disease.

PMID- 21941215
TI  - Maternal characteristics and hospital policies as risk factors for nonreceipt of
      hepatitis B vaccine in the newborn nursery.
AB  - BACKGROUND: A birth dose of hepatitis B vaccine (HBV) is a primary focus of the
      Advisory Committee on Immunization Practices' strategy to eliminate transmission
      of hepatitis B virus in the United States. We sought to assess the impact of
      maternal characteristics and hospital policy on the receipt of a birth dose of
      HBV. METHODS: A retrospective cohort study was performed using data from the 2008
      Colorado birth registry. Hospital policy was assessed by state health department
      personnel. Univariate and multivariate logistic regression analyses were used to
      examine the association of maternal characteristics and hospital policy with
      nonreceipt of HBV. RESULTS: A total of 64,425 infants were identified in the
      birth cohort, of whom 61.6% received a birth dose of HBV. Higher maternal
      education and income were associated with nonreceipt of HBV (master's degree vs.
      eighth grade or less: adjusted odds ratio [OR] = 1.66, 95% confidence interval
      [CI] = 1.49-1.85; >$75,000 vs. <$15,000: adjusted OR = 1.21, 95% CI = 1.13-1.30).
      Lack of a hospital policy stipulating a universal birth dose strongly predicted
      nonreceipt of a birth dose of HBV (policy with no birth dose vs. policy with a
      birth dose: adjusted OR = 2.21, 95% CI = 2.13-2.30). CONCLUSIONS: Maternal
      characteristics such as higher education and income are associated with
      nonreceipt of the HBV during the perinatal period. To effectively reduce risk of
      perinatal hepatitis B transmission, hospitals should stipulate that all infants
      are offered HBV and ensure that these policies are implemented and followed.

PMID- 21941216
TI  - Life-threatening pneumonia caused by macrolide-resistant Mycoplasma pneumoniae.
AB  - Two siblings had pneumonia caused by macrolide-resistant Mycoplasma pneumoniae as
      determined by polymerase chain reaction and serology. One of them developed adult
      respiratory distress syndrome and required extracorporeal membrane oxygenation
      therapy. This report highlights the need for studies to evaluate the optimal
      treatment in severe cases of macrolide-resistant M. pneumoniae pneumonia.

PMID- 21941217
TI  - The transmission of tuberculosis in schools involving children 3 to 11 years of
      age.
AB  - Little is known about the risk of tuberculosis transmission from children. We
      reviewed the published literature on the transmission of tuberculosis during
      outbreaks involving children 3 to 11 years of age and report that transmission
      rates among close contacts in school outbreaks are on average higher (weighted
      average 69.8% vs. 39.3%) if the index case is a child than an adult.

PMID- 21941218
TI  - Daniel C. Moore, MD, and the renaissance of regional anesthesia in North America.
AB  - While much attention is paid to the early days of organized regional anesthesia
      in North America under the leadership of Gaston Labat in New York, there was a
      period of decline in energy and activity in those techniques after the demise of
      his original American Society of Regional Anesthesia in 1940. In the years after
      World War II, questions were raised about the safety and utility of regional
      blockade. Dr. Daniel C. Moore emerged as a colorful and enthusiastic advocate of
      regional techniques, effectively leading a renaissance of regional anesthesia
      interest through his textbook, teaching, and research in Seattle, Washington. His
      proteges were instrumental in the rebirth of American Society of Regional
      Anesthesia and the extensive spread of regional anesthesia today.

PMID- 21941219
TI  - Ultrasound-guided versus anatomic landmark-guided ankle blocks: a 6-year
      retrospective review.
AB  - BACKGROUND AND OBJECTIVES: Ultrasound-guided (USG) ankle block has been
      described; however, its clinical efficacy compared with conventional anatomic
      landmark-guided (ALG) techniques remains undetermined. METHODS: We performed a 6
      year retrospective cohort study of all ankle blocks performed for foot surgery
      and extracted demographic, intraoperative, and postoperative outcome data. We
      divided blocks into 2 groups for comparison, depending on whether they were
      performed using an ALG technique or a USG technique. RESULTS: We identified 655
      patients who received unilateral ankle block and 58 patients who received
      bilateral ankle block; we analyzed these separately. Trainees performed most
      blocks (approximately 80%). In patients receiving unilateral ankle block,
      successful surgical anesthesia was more likely in the USG group (84% versus 66%,
      P < 0.001). Patients in the ALG group were more likely to require supplemental
      local anesthesia (10% versus 5%, P = 0.04), unplanned general anesthesia (17%
      versus 7%, P = 0.001), or supplemental fentanyl (18% versus 9%, P = 0.002).
      Postanesthetic care unit pain scores were similar between groups. However,
      patients in the ALG group were more likely to receive intravenous opioids (21%
      versus 12%, P = 0.01), and they received a higher mean opioid dose (10.6 versus
      8.7 mg intravenous morphine, ALG versus USG, P = 0.022). In patients receiving
      bilateral ankle block, successful surgical anesthesia was also more likely in the
      USG group (84% versus 57%); however, this was not statistically significant
      because of the small sample size. CONCLUSIONS: This study demonstrates that the
      USG technique of ankle block improves clinical efficacy compared with a
      conventional ALG technique, particularly in the hands of less-experienced
      practitioners.

PMID- 21941220
TI  - A translational study of the effects of ketamine and pregabalin on temporal
      summation of experimental pain.
AB  - BACKGROUND AND OBJECTIVES: Central sensitization is often seen in chronic pain. A
      relevant and potent mechanism of central sensitization is the central integration
      of nociceptive impulses. Temporal summation in humans and the wind-up process in
      animals share common features of central integration. This preclinical and
      clinical translational study investigated the effect of ketamine and pregabalin
      on temporal summation (TS) and wind-up of wide dynamic range (WDR) neurons of
      nociceptive electrical stimuli in healthy volunteers and rats. METHODS: This 3
      way crossover study included healthy male volunteers (n = 18) receiving 3 doses
      of 300 mg pregabalin (orally) over 2 days, ketamine (intravenous loading dose 0.5
      mg/kg followed by 9 MUg/kg per minute for 20 mins) on the first day, or placebo.
      The pain detection thresholds to repetitive electrical cutaneous and
      suprathreshold responses stimulation were assessed.In male Sprague-Dawley rats (n
      = 30), WDR neuron recordings after electrical stimulation were obtained before
      and after 15 minutes of intravenous infusion pregabalin (0.127, 0.42, and 1.27
      mg/kg per minute) and ketamine (0.006, 0.02, 0.06, and 0.2 mg/kg per minute).
      RESULTS: In the human study, ketamine compared with placebo significantly
      increased the TS pain detection threshold (P < 0.001) and significantly reduced
      suprathreshold pain responses (P < 0.001). In rats, the highest dose of ketamine
      significantly inhibited the wind-up response of the WDR neurons (P = 0.014).
      Pregabalin affected neither of the parameters in TS and WDR responses.
      CONCLUSIONS: It was shown that TS shares common features with wind-up of WDR
      neurons and that pregabalin does not affect this component of central
      sensitization.

PMID- 21941221
TI  - Are sympathetic blocks useful for diagnostic purposes?
AB  - BACKGROUND: Sympathetically maintained pain (SMP) can occur in patients with
      neuropathic pain. Sympathetically maintained pain is frequently diagnosed
      clinically by assessing the analgesic effect of an appropriate sympathetic block
      (SB). The diagnostic value of such blocks depends on both the degree of
      sympathetic activity disruption achieved and its duration without unintentional
      concomitant sensory block. METHODS: This pilot study evaluated the rate of
      diagnostically valuable SBs performed by experienced anesthesiologists in 19
      patients (stellate/thoracic blocks: n = 11, lumbar blocks: n = 12). Monitoring
      included pain rating before SB; 10 and 30 minutes; and at 1, 3, and 6 hours after
      SB; bilateral skin temperature 30 minutes before SB through 120 minutes after SB;
      and detection of bilateral thresholds for cold, warmth, tactile, and vibration
      stimuli before and after. RESULTS: Ten (43%) of 23 SBs were not eligible for SMP
      diagnosis (4 had insufficient skin temperature increase; and 6 had cold or
      tactile detection threshold increases in the painful area). In 11 of the SBs, no
      significant sensory threshold change was detected; however, 2 individuals
      demonstrated marked reductions in the cold or tactile sensory thresholds.
      Sympathetically maintained pain was diagnosed in 3 (25%) of the 12 patients who
      had at least 1 SB with the required skin temperature increase without concomitant
      somatosensory block. CONCLUSIONS: Sympathetic blocks are useful in the diagnosis
      of SMP. However, their value is limited by the potential for false positives
      (unintentional sensory block) or false negatives (insufficient SB). Adequate
      monitoring of the sympathetic and somatosensory function for a minimum of 90
      minutes after the intervention is essential to ensure that a valid diagnosis of
      SMP is made.

PMID- 21941222
TI  - Comparison of mortality associated with sepsis in the burn, trauma, and general
      intensive care unit patient:  a systematic review of the literature.
AB  - The purpose of this systematic review of the literature was to determine the
      association of sepsis with mortality in the severely injured adult patient by
      means of a comparative analysis of sepsis in burn and trauma injury with other
      critically ill populations. The MEDLINE (PubMed), Cochrane Library, and ProQuest
      databases were searched. The following keywords and MeSH headings were used:
      "sepsis," septicemia," "septic shock," "epidemiology," "burns," "thermal injury,"
      "trauma," "wounds and injuries," "critical care," "intensive care," "outcomes,"
      and "mortality." Included studies were clinical studies of adult burn, trauma,
      and critically ill patients that reported survival data for sepsis. Thirty-eight
      articles were reviewed (9 burn, 11 trauma, 18 general critical care). The age of
      burn (<45 years) and trauma (34-49 years) groups was lower than the general
      critical care (57-64 years) population. Sepsis prevalence varied with trauma
      injured patients experiencing fewer episodes (2.4%-16.9%) contrasted with burn
      patients (8%-42.5%) and critical care patients (19%-38%). Survival differed with
      trauma patients experiencing a lower rate of mortality associated with sepsis (7%
      36.9%) compared with the burn (28%-65%) and critical care (21%-53%) groups. This
      study is the first to compare sepsis outcomes in three distinct patient
      populations: burn, trauma, and general critical care. Trauma patients tend to
      have relatively low sepsis-associated mortality; burn patients and the older
      critical care population have higher prevalence of sepsis with worse outcomes.
      Great variability of criteria to identify septic patients among studies
      compromises population comparisons.

PMID- 21941223
TI  - Preventing enterocyte damage by maintenance of mean arterial pressure during
      major nonabdominal surgery in children.
AB  - Loss of the gut barrier, which is related to hypotension and gastrointestinal
      hypoperfusion during surgery, has been implicated as a critical event in
      postoperative complications development. This study aims at preventing gut
      barrier loss by maintenance of mean arterial pressure (MAP) in patients
      undergoing major nonabdominal surgery. In 20 previously included children
      undergoing spinal fusion surgery, the critical MAP value, which should be
      maintained to prevent enterocyte damage, was determined. In the following 12
      children, MAP was kept above the critical value during surgery. Gut mucosal
      barrier loss was assessed by plasma intestinal fatty acid-binding proteins
      levels, a marker for enterocyte damage. Gastrointestinal perfusion was measured
      by gastric tonometry. First, we determined that the MAP should be maintained
      greater than 60 mmHg to prevent enterocyte damage. Next, maintenance of the MAP
      above this critical value during surgery resulted in adequate intestinal
      perfusion and preservation of enterocyte integrity, represented by intestinal
      fatty acid-binding protein levels within the reference range. This study shows
      that maintenance of the MAP at greater than 60 mmHg is associated with adequate
      intestinal perfusion and reduced enterocyte loss in children undergoing major
      nonabdominal surgery. These data stress the importance and benefits of good
      circulatory management during major surgery.

PMID- 21941224
TI  - Modifications in erythrocyte membrane protein content are not responsible for the
      alterations in rheology seen in sepsis.
AB  - Red blood cell (RBC) rheology is altered in sepsis and may contribute to the
      microcirculatory alterations in these patients, but the mechanisms of these
      changes are not well defined. An increase in the RBC protein band 3/alpha
      spectrin ratio has been observed in a mouse model of septic shock, suggesting a
      possible alteration in the RBC membrane integral/peripheral protein ratio. This
      protein modification could contribute to the alterations in RBC rheology observed
      in sepsis. As there are interspecies differences in membrane composition, these
      observations need confirmation in humans. We studied RBCs from healthy volunteers
      (n = 10) and from patients with (n = 15) and without (n = 9) sepsis within 24 h
      of intensive care unit admission and also on day 3 for the septic patients.
      Exclusion criteria were recent RBC transfusion, hematologic diseases, cirrhosis,
      and diabetes mellitus. Procedures included screening for alterations in RBC
      membrane proteins using cryohemolysis and separation of RBC membrane and skeletal
      proteins by polyacrylamide gel electrophoresis in the presence of sodium dodecyl
      sulfate. The hemogram, including reticulocyte count, was similar between
      nonseptic and septic patients on day 1. The majority of RBC membrane protein
      ratios, including band 3/spectrin, were more elevated in critically ill patients
      (nonseptic and septic) than in volunteers, but RBC membrane skeletal protein
      content was similar in septic and nonseptic patients. There were no significant
      differences in cryohemolysis results among groups. Alterations in RBC rheology in
      sepsis are therefore mainly due to alterations in membrane compounds other than
      skeletal proteins, like carbohydrates, such as sialic acid and/or lipids.

PMID- 21941225
TI  - Doubling of serum creatinine in clinical trials, cost-effectiveness studies, and
      individual patients: adequate use in renal transplantation.
AB  - BACKGROUND: The predictive value of doubling of serum creatinine (DSC) has never
      been assessed in renal transplantation. We evaluated it in terms of its use for
      clinical trials, cost-effectiveness studies, and individual patients. METHODS:
      Retrospective longitudinal study in 896 renal transplant recipients. RESULTS:
      Death-censored graft loss occurred in 133 patients, during follow-up (up to 21
      years). DSC was a risk factor for graft loss; however, the relative risk was
      different in patients with glomerular filtration rate less than 40 vs. more than
      or equal to 40 mL/min (hazard ratio: 14.5 [95% confidence interval: 7.4-28.4] vs.
      47.8 [28.4-80.6], P=0.0051). Parameters influencing creatinine value (weight,
      age, sex) did not modify DSC's predictive value. The use of the composite
      endpoint DSC or death-censored graft loss instead of death-censored graft loss
      alone in clinical trials would reduce sample size by 7.1% to 9.0%. The annual
      probability of DSC to graft loss transition decreased from 76% (follow-up <1
      year) to 5% (follow-up >=10 years). Median graft half-life after DSC was 10
      months [95% confidence interval: 6-18] but varied with increasing time to DSC (<1
      year: 1 month [0.5-6]; 3-4.9 years: 15 months 5/67) and reference creatinine
      (<130 MUmol/L: 3 months 2/6); >=130 MUmol/L: 25 months 15/37). CONCLUSIONS: DSC
      may be adequately used to refine the risk of death-censored graft loss for
      individual patients. However, the use of DSC as an endpoint in clinical trials
      marginally affects sample size, and the probability of DSC to graft loss
      transition is not constant, which limits the use of DSC in cost-effectiveness
      analyses of renal transplantation.

PMID- 21941226
TI  - A universal preemptive therapy for cytomegalovirus infections in children after
      live-donor liver transplantation.
AB  - BACKGROUND: Cytomegalovirus (CMV) infection remains the most common and critical
      viral infection that occurs after liver transplantation (LT). The current set of
      guidelines recommends prophylaxis over a preemptive therapy for pediatric LT;
      however, the data regarding the optimal approach after LT in children are
      limited. METHODS: We conducted a universal preemptive therapy for CMV infection
      in 113 children (median: 16 months) after live-donor LT at the largest pediatric
      LT center in Japan between November 2005 and August 2009. CMV-pp65 antigenemia
      was monitored weekly regardless of the subjects' CMV serostatus after LT, and
      ganciclovir therapy was initiated when CMV-pp65 antigenemia was positive.
      RESULTS: The overall success rate of LT was 91.7%. CMV-pp65 antigenemia became
      positive in 37 (33%) recipients, and the positivity with their CMV serostatus was
      as follows: donor (D)+/recipient (R)-: 62%, D+/R+: 36%, D-/R+: 11%, and D-/R-:
      8%. Among the D+/R- (n=29) and D+/R+ (n=44) recipients, 38% (n=11) and 64% (n=28)
      recipients were able to avoid the use of ganciclovir, respectively. Human CMV
      disease was documented in six (5%) recipients, and they were successfully treated
      with ganciclovir without any sequelae. CONCLUSIONS: A universal preemptive
      therapy for CMV infection after live-donor LT was successful for reducing the use
      of antiviral agents and for controlling CMV infection and disease in children.

PMID- 21941227
TI  - Thermodynamic study of the complexation of p-isopropylcalix[6]arene with Cs+
      cation in dimethylsulfoxide-acetonitrile binary media.
AB  - The complexation reactions between the macrocyclic ionophore, p
      isopropylcalix[6]arene and Cs+ cation were studied in dimethylsulfoxide
      acetonitrile (DMSO-AN) binary non-aqueous solvents at different temperatures
      using a conductometry method. The conductance data show that the stoichiometry of
      the (p-isopropylcalix[6]-arene.Cs)+ complex in all binary mixed solvents is 1:1.
      The stability of the complexes is affected by the composition of the binary
      solvent media and a non-linear behavior was observed for changes of log K(f) of
      the complex versus the composition of the binary mixed solvents. The
      thermodynamic parameters (DH degrees (c) and DS degrees (c)) for formation of (p
      isopropyl-calix[6]arene.Cs)+ complex were obtained from temperature dependence of
      the stability constant and the obtained results show that the (p
      isopropylcalix[6]arene.Cs)+ complex is enthalpy destabilized, but entropy
      stabilized, and the values of the mentioned parameters are affected strongly by
      the nature and composition of the binary mixed solvents.

PMID- 21941228
TI  - Antithrombotic drugs.

PMID- 21941229
TI  - Relationship between birth weight and retinal microvasculature in newborn
      infants.
AB  - OBJECTIVE: The purposes of this study were to determine the normal retinal
      microvasculature measurements in human infants who are born at term and to
      determine whether birth weight influences measurements of retinal
      microvasculature. STUDY DESIGN: Retinal arteriole and venule measurements were
      obtained in a cohort of 24 infants who were born at term. Digital images of both
      the retinas were obtained using a digital retinal camera after pupillary
      dilation. RESULT: In all, 24 newborn infants born at term (12 females and 12
      males) were analyzed in this study. The measured retinal arteriole diameters were
      from 66.8 to 147.8 MUm (mean, 94.2+/-19.6 MUm), and the venule diameters were
      from 102.0 to 167.8 MUm (mean, 135.2+/-19.1 MUm). Seven babies in the sample had
      low birth weight (LBW), while 17 babies were born with normal weight. Babies with
      lower birth weights had larger arteriole (113.1+/-17.9 MUm vs 86.4+/-14.4 MUm;
      P=0.0009) and venule diameters (151.7+/-14.9 MUm vs 128.4+/-16.9 MUm; P=0.0040).
      CONCLUSION: Retinal venules and arterioles in LBW babies are larger compared with
      those of normal-birth-weight babies. We postulate that the difference observed in
      our study was due to in utero pathophysiological changes that occurred in the
      cerebral circulation of growth-restricted fetuses.

PMID- 21941230
TI  - Sildenafil citrate, bronchopulmonary dysplasia and disordered pulmonary gas
      exchange: any benefits?
AB  - OBJECTIVE: The objective of this study is to determine the effects that
      sildenafil citrate has on gas exchange in infants with bronchopulmonary dysplasia
      (BPD)-associated pulmonary hypertension (PH). STUDY DESIGN: A retrospective
      review was performed from 2005 to 2009. Infants treated with sildenafil citrate
      for greater than 48  h were included. Standard patient data was collected,
      including echocardiogram, inspired oxygen and systemic blood pressure, before and
      during administration of sildenafil citrate. RESULT: Sildenafil citrate was used
      in 21 preterm infants with BPD-associated PH. A significant reduction in
      estimated right ventricular peak systolic pressure was seen after initiation of
      sildenafil citrate, with the majority of infants showing no improvement in gas
      exchange at 48  h of treatment. Four infants died during treatment. CONCLUSION:
      Sildenafil citrate reduced estimated pulmonary artery pressures, but this
      reduction was not reflected in improved gas exchange within the first 48  h.

PMID- 21941231
TI  - A randomized trial of the Vein Viewer versus standard technique for placement of
      peripherally inserted central catheters (PICCs) in neonates.
AB  - OBJECTIVE: Peripherally inserted central catheters are important but can be
      difficult to place in neonates. Therefore, we compared a near-infrared device,
      the Vein Viewer, to determine if its use would increase successful line
      placement, with standard techniques. STUDY DESIGN: Randomized controlled trial in
      preterm and term neonates in a level 3 Neonatal Intensive Care Unit. RESULT: In
      all, 115 subjects were enrolled with 59 randomized to the Vein Viewer group and
      56 to the control group. Overall, use of the Vein Viewer showed a trend to more
      successful placement 86 versus 75%; unadjusted odds ratio 2.33 (0.90, 6.04;
      P=0.08). Infants randomized to the Vein Viewer were more mature (30 +/- 2 weeks
      gestational age (GA) versus 28 +/- 2 weeks GA; P=0.08). After adjusting for GA,
      use of the Vein Viewer was significantly more likely to lead to successful line
      placement (adjusted odds ratio 3.05 (1.10, 1.82)). CONCLUSION: The Vein Viewer
      improved successful placement with the most benefit seen in infants of greater
      GA.

PMID- 21941232
TI  - Renin is activated in monochorionic diamniotic twins with birthweight discordance
      who do not have twin-to-twin transfusion syndrome.
AB  - OBJECTIVE: To assess renin, aldosterone, human atrial natriuretic peptide (hANP)
      and brain natriuretic peptide (BNP) levels in cord blood from monochorionic
      diamniotic (MD) twins with a birthweight (BW) discordance that do not satisfy the
      criteria of twin-to-twin transfusion syndrome (TTTS). STUDY DESIGN: Cord blood
      samples were obtained from 28 MD twins without TTTS. They were divided into two
      groups on the basis of BW discordance as follows: large (>7.5%) and small
      (?7.5%). Cord blood renin, aldosterone, hANP and BNP levels were measured.
      RESULT: Renin levels in MD twins with a large BW discordance were significantly
      higher than those in MD twins with a small BW discordance, with no significant
      differences in aldosterone, hANP and BNP levels. A significant correlation was
      found between renin levels and BW discordance. CONCLUSION: Renin is activated in
      MD twins with a BW discordance of >7.5%, even in non-TTTS.

PMID- 21941233
TI  - Delivery room resuscitation of preterm infants in Canada: current practice and
      views of neonatologists at level III centers.
AB  - OBJECTIVE: To explore physicians' experiences and views related to resuscitation
      practice of preterm infants at birth, and determine whether the Canadian
      modifications of 2006 Neonatal Resuscitation Program (NRP) guidelines have been
      accepted by neonatologists. STUDY DESIGN: Neonatologists (n=146) at 25 tertiary
      neonatal intensive care units (NICUs) across Canada were contacted via email to
      participate in a web-based survey about their practice regarding resuscitation of
      preterm infants in the delivery room (DR). RESULT: In all, 78 respondents (53%)
      from 23 centres completed the survey. Participants reported significant
      variability in temperature control measures. Hypothermia, <36.5  degrees C on
      NICU admission, was reported by 49% of respondents. Room air is used by 59% of
      respondents to initiate resuscitation. The majority (91%) of participants use
      pulse oximetry to titrate oxygen administration. Although more than two thirds
      (69%) of respondents target an oxygen saturation range of 85 to 92%, 51% of
      respondents would allow 5 to 10 min for the oxygen saturation to reach the target
      level. Carbon dioxide detectors are commonly used to confirm endotracheal tube
      placement (90%). Although respondents (96%) agree on the use of positive end-
      expiratory pressure (PEEP), when providing positive pressure ventilation (PPV),
      only 60% would initiate PPV with a pre-set peak inspiratory pressure, mostly 20
      cm H(2)O. CONCLUSION: DR resuscitation practices are highly variable in Canadian
      NICU's and the currently recommended NRP guidelines are not uniformly followed.
      Factors leading to variability and discordance in practice should be investigated
      to facilitate better compliance.

PMID- 21941234
TI  - Open science is a research accelerator.

PMID- 21941235
TI  - A tale of two compounds.

PMID- 21941242
TI  - Single-molecule biophysics: untying a nanoscale knot.

PMID- 21941243
TI  - Synthetic biology: minimal cell mimicry.

PMID- 21941244
TI  - Catalysis: oxidizing water two ways.

PMID- 21941245
TI  - Ionothermal synthesis: a new spin on frustration.

PMID- 21941246
TI  - Protein NMR spectroscopy: spinning into focus.

PMID- 21941247
TI  - Iron-oxo complexes: elusive iron(V) species identified.

PMID- 21941248
TI  - Lessons from nature about solar light harvesting.
AB  - Solar fuel production often starts with the energy from light being absorbed by
      an assembly of molecules; this electronic excitation is subsequently transferred
      to a suitable acceptor. For example, in photosynthesis, antenna complexes capture
      sunlight and direct the energy to reaction centres that then carry out the
      associated chemistry. In this Review, we describe the principles learned from
      studies of various natural antenna complexes and suggest how to elucidate
      strategies for designing light-harvesting systems. We envisage that such systems
      will be used for solar fuel production, to direct and regulate excitation energy
      flow using molecular organizations that facilitate feedback and control, or to
      transfer excitons over long distances. Also described are the notable properties
      of light-harvesting chromophores, spatial-energetic landscapes, the roles of
      excitonic states and quantum coherence, as well as how antennas are regulated and
      photoprotected.

PMID- 21941249
TI  - Self-reproduction of supramolecular giant vesicles combined with the
      amplification of encapsulated DNA.
AB  - The construction of a protocell from a materials point of view is important in
      understanding the origin of life. Both self-reproduction of a compartment and
      self-replication of an informational substance have been studied extensively, but
      these processes have typically been carried out independently, rather than linked
      to one another. Here, we demonstrate the amplification of DNA (encapsulated
      guest) within a self-reproducible cationic giant vesicle (host). With the
      addition of a vesicular membrane precursor, we observe the growth and spontaneous
      division of the giant vesicles, accompanied by distribution of the DNA to the
      daughter giant vesicles. In particular, amplification of the DNA accelerated the
      division of the giant vesicles. This means that self-replication of an
      informational substance has been linked to self-reproduction of a compartment
      through the interplay between polyanionic DNA and the cationic vesicular
      membrane. Our self-reproducing giant vesicle system therefore represents a step
      forward in the construction of an advanced model protocell.

PMID- 21941250
TI  - A single-molecule platform for investigation of interactions between G
      quadruplexes and small-molecule ligands.
AB  - Ligands that stabilize the formation of telomeric DNA G-quadruplexes have
      potential as cancer treatments, because the G-quadruplex structure cannot be
      extended by telomerase, an enzyme over-expressed in many cancer cells.
      Understanding the kinetic, thermodynamic and mechanical properties of small
      molecule binding to these structures is therefore important, but classical
      ensemble assays are unable to measure these simultaneously. Here, we have used a
      laser tweezers method to investigate such interactions. With a force jump
      approach, we observe that pyridostatin promotes the folding of telomeric G
      quadruplexes. The increased mechanical stability of pyridostatin-bound G
      quadruplex permits the determination of a dissociation constant K(d) of 490 +/-
      80 nM. The free-energy change of binding obtained from a Hess-like process
      provides an identical K(d) for pyridostatin and a K(d) of 42 +/- 3 uM for a
      weaker ligand RR110. We anticipate that this single-molecule platform can provide
      detailed insights into the mechanical, kinetic and thermodynamic properties of
      liganded bio-macromolecules, which have biological relevance.

PMID- 21941251
TI  - Observation of Fe(V)=O using variable-temperature mass spectrometry and its
      enzyme-like C-H and C=C oxidation reactions.
AB  - Oxo-transfer chemistry mediated by iron underpins many biological processes and
      today is emerging as synthetically very important for the catalytic oxidation of
      C-H and C=C moieties that are hard to activate conventionally. Despite the vast
      amount of research in this area, experimental characterization of the reactive
      species under catalytic conditions is very limited, although a Fe(V)=O moiety was
      postulated. Here we show, using variable-temperature mass spectrometry, the
      generation of a Fe(V)=O species within a synthetic non-haem complex at -40 
      degrees C and its reaction with an olefin. Also, with isotopic labelling we were
      able both to follow oxygen-atom transfer from H(2)O(2)/H(2)O through Fe(V)=O to
      the products and to probe the reactivity as a function of temperature. This study
      pioneers the implementation of variable-temperature mass spectrometry to
      investigate reactive intermediates.

PMID- 21941253
TI  - An ionothermally prepared S = 1/2 vanadium oxyfluoride kagome lattice.
AB  - Frustrated magnetic lattices offer the possibility of many exotic ground states
      that are of great fundamental importance. Of particular significance is the hunt
      for frustrated spin-1/2 networks as candidates for quantum spin liquids, which
      would have exciting and unusual magnetic properties at low temperatures. The few
      reported candidate materials have all been based on d(9) ions. Here, we report
      the ionothermal synthesis of [NH(4)](2)[C(7)H(14)N][V(7)O(6)F(18)], an inorganic
      organic hybrid solid that contains a S = 1/2 kagome network of d(1) V(4+) ions.
      The compound exhibits a high degree of magnetic frustration, with significant
      antiferromagnetic interactions but no long-range magnetic order or spin-freezing
      above 2 K, and appears to be an excellent candidate for realizing a quantum spin
      liquid ground state in a spin-1/2 kagome network.

PMID- 21941252
TI  - Reversible bond formation enables the replication and amplification of a
      crosslinking salen complex as an orthogonal base pair.
AB  - The universal genetic code relies on two hydrogen-bonded Watson-Crick base pairs
      that can form 64 triplet codons. This places a limit on the number of amino acids
      that can be encoded, which has motivated efforts to create synthetic base pairs
      that are orthogonal to the natural ones. An additional base pair would result in
      another 61 triplet codons. Artificial organic base pairs have been described in
      enzymatic incorporation studies, and inorganic T-Hg-T and C-Ag-C base pairs have
      been reported to form in primer extension studies. Here, we demonstrate a metal
      base pair that is fully orthogonal and can be replicated, and can even be
      amplified by polymerase chain reaction in the presence of the canonical pairs
      dA:dT and dG:dC. Crystal structures of a dS-Cu-dS base pair inside a polymerase
      show that reversible chemistry is possible directly inside the polymerase, which
      enables the efficient copying of the inorganic crosslink. The results open up the
      possibility of replicating and amplifying artificial inorganic DNA nanostructures
      by extending the genetic alphabet.

PMID- 21941254
TI  - Efficient water oxidation catalysts based on readily available iron coordination
      complexes.
AB  - Water oxidation catalysis constitutes the bottleneck for the development of
      energy-conversion schemes based on sunlight. To date, state-of-the-art
      homogeneous water oxidation catalysis is performed efficiently with expensive,
      toxic and earth-scarce transition metals, but 3d metal-based catalysts are much
      less established. Here we show that readily available, environmentally benign
      iron coordination complexes catalyse homogeneous water oxidation to give O(2),
      with high efficiency during a period of hours. Turnover numbers >350 and >1,000
      were obtained using cerium ammonium nitrate at pH 1 and sodium periodate at pH 2,
      respectively. Spectroscopic monitoring of the catalytic reactions, in combination
      with kinetic studies, show that high valent oxo-iron species are responsible for
      the O-O forming event. A systematic study of iron complexes that contain a broad
      family of neutral tetradentate organic ligands identifies first-principle
      structural features to sustain water oxidation catalysis. Iron-based catalysts
      described herein open a novel strategy that could eventually enable sustainable
      artificial photosynthetic schemes.

PMID- 21941255
TI  - Molecular heterometallic hydride clusters composed of rare-earth and d-transition
      metals.
AB  - Heteromultimetallic hydride clusters containing both rare-earth and d-transition
      metals are of interest in terms of both their structure and reactivity. However,
      such heterometallic complexes have not yet been investigated to a great extent
      because of difficulties in their synthesis and structural characterization. Here,
      we report the synthesis, X-ray and neutron diffraction studies, and hydrogen
      addition and release properties of a family of rare-earth/d-transition-metal
      heteromultimetallic polyhydride complexes of the core structure type 'Ln(4)MH(n)'
      (Ln = Y, Dy, Ho; M = Mo, W; n = 9, 11, 13). Monitoring of hydrogen addition to a
      hydride cluster such as [{(C(5)Me(4)SiMe(3))Y}(4)(MU-H)(9)Mo(C(5)Me(5))] in a
      single-crystal to single-crystal process by X-ray diffraction has been achieved
      for the first time. Density functional theory studies reveal that the hydrogen
      addition process is cooperatively assisted by the Y/Mo heteromultimetallic sites,
      thus offering unprecedented insight into the hydrogen addition and release
      process of a metal hydride cluster.

PMID- 21941259
TI  - Anisotropic dysprosium.

PMID- 21941256
TI  - Multi-hierarchical self-assembly of a collagen mimetic peptide from triple helix
      to nanofibre and hydrogel.
AB  - Replicating the multi-hierarchical self-assembly of collagen has long-attracted
      scientists, from both the perspective of the fundamental science of
      supramolecular chemistry and that of potential biomedical applications in tissue
      engineering. Many approaches to drive the self-assembly of synthetic systems
      through the same steps as those of natural collagen (peptide chain to triple
      helix to nanofibres and, finally, to a hydrogel) are partially successful, but
      none simultaneously demonstrate all the levels of structural assembly. Here we
      describe a peptide that replicates the self-assembly of collagen through each of
      these steps. The peptide features collagen's characteristic proline
      hydroxyproline-glycine repeating unit, complemented by designed salt-bridged
      hydrogen bonds between lysine and aspartate to stabilize the triple helix in a
      sticky-ended assembly. This assembly is propagated into nanofibres with
      characteristic triple helical packing and lengths with a lower bound of several
      hundred nanometres. These nanofibres form a hydrogel that is degraded by
      collagenase at a similar rate to that of natural collagen.

PMID- 21941260
TI  - Not a clear cut.

PMID- 21941266
TI  - Crystalline ice: Amorphous on the surface.

PMID- 21941267
TI  - Superconductivity: An X-ray oxygen regulator.

PMID- 21941268
TI  - Protein-patterned hydrogels: Customized cell microenvironments.

PMID- 21941269
TI  - Photoemission spectroscopy: Deep into the bulk.

PMID- 21941270
TI  - Material witness: A quick fix.

PMID- 21941272
TI  - Cell division: CENPA's tail rules the centromere.

PMID- 21941274
TI  - Membrane dynamics: ER marks the spot.

PMID- 21941276
TI  - A decade of molecular cell biology: achievements and challenges.
AB  - Nature Reviews Molecular Cell Biology celebrated its 10-year anniversary during
      this past year with a series of specially commissioned articles. To complement
      this, here we have asked researchers from across the field for their insights
      into how molecular cell biology research has evolved during this past decade, the
      key concepts that have emerged and the most promising interfaces that have
      developed. Their comments highlight the broad impact that particular advances
      have had, some of the basic understanding that we still require, and the
      collaborative approaches that will be essential for driving the field forward.

PMID- 21941275
TI  - Proteins on the move: insights gained from fluorescent protein technologies.
AB  - Proteins are always on the move, and this may occur through diffusion or active
      transport. The realization that the regulation of signal transduction is highly
      dynamic in space and time has stimulated intense interest in the movement of
      proteins. Over the past decade, numerous new technologies using fluorescent
      proteins have been developed, allowing us to observe the spatiotemporal dynamics
      of proteins in living cells. These technologies have greatly advanced our
      understanding of protein dynamics, including protein movement and protein
      interactions.

PMID- 21941278
TI  - Layers of regulation.

PMID- 21941277
TI  - Discovering pluripotency: 30 years of mouse embryonic stem cells.
AB  - Embryonic stem (ES) cells are pluripotent cells isolated from an early embryo and
      grown as a cell line in tissue culture. Their discovery came from the conjunction
      of studies in human pathology, mouse genetics, early mouse embryo development,
      cell surface immunology and tissue culture. ES cells provided a crucial tool for
      manipulating mouse embryos to study mouse genetics, development and physiology.
      They have not only revolutionized experimental mammalian genetics but, with the
      advent of equivalent human ES cells, have now opened new vistas for regenerative
      medicine.

PMID- 21941280
TI  - Targeting MYC? You BET.

PMID- 21941281
TI  - Perineural invasion and associated pain in pancreatic cancer.
AB  - Perineural invasion (PNI) is a prominent characteristic of pancreatic cancer. PNI
      is a process whereby cancer cells invade the surrounding nerves, thus providing
      an alternative route for metastatic spread and pain generation. PNI is thought to
      be an indicator of aggressive tumour behaviour and has been shown to correlate
      with poor prognosis of patients with pancreatic cancer. Recent studies
      demonstrated that some signalling molecules and pathways that are involved in PNI
      are also involved in pain generation. Targeting these signalling pathways has
      shown some promise in alleviating pain and reducing PNI, which could potentially
      improve treatment outcomes for patients with pancreatic cancer.

PMID- 21941282
TI  - Aminoacyl-tRNA synthetases and tumorigenesis: more than housekeeping.
AB  - Over the past decade, the identification of cancer-associated factors has been a
      subject of primary interest not only for understanding the basic mechanisms of
      tumorigenesis but also for discovering the associated therapeutic targets.
      However, aminoacyl-tRNA synthetases (ARSs) have been overlooked, mostly because
      many assumed that they were simply 'housekeepers' that were involved in protein
      synthesis. Mammalian ARSs have evolved many additional domains that are not
      necessarily linked to their catalytic activities. With these domains, they
      interact with diverse regulatory factors. In addition, the expression of some
      ARSs is dynamically changed depending on various cellular types and stresses.
      This Analysis article addresses the potential pathophysiological implications of
      ARSs in tumorigenesis.

PMID- 21941283
TI  - Rethinking ovarian cancer: recommendations for improving outcomes.
AB  - There have been major advances in our understanding of the cellular and molecular
      biology of the human malignancies that are collectively referred to as ovarian
      cancer. At a recent Helene Harris Memorial Trust meeting, an international group
      of researchers considered actions that should be taken to improve the outcome for
      women with ovarian cancer. Nine major recommendations are outlined in this
      Opinion article.

PMID- 21941286
TI  - Immunotherapy: Leukadherins get a grip on inflammation.

PMID- 21941284
TI  - A decade of exploring the cancer epigenome - biological and translational
      implications.
AB  - The past decade has highlighted the central role of epigenetic processes in
      cancer causation, progression and treatment. Next-generation sequencing is
      providing a window for visualizing the human epigenome and how it is altered in
      cancer. This view provides many surprises, including linking epigenetic
      abnormalities to mutations in genes that control DNA methylation, the packaging
      and the function of DNA in chromatin, and metabolism. Epigenetic alterations are
      leading candidates for the development of specific markers for cancer detection,
      diagnosis and prognosis. The enzymatic processes that control the epigenome
      present new opportunities for deriving therapeutic strategies designed to reverse
      transcriptional abnormalities that are inherent to the cancer epigenome.

PMID- 21941288
TI  - Phagocytosis: Phagocytes whet their appetite.

PMID- 21941289
TI  - Tumour immunology: Neutrophils fight back in the final round.

PMID- 21941292
TI  - Natural killer T cells: Worth holding on to.

PMID- 21941285
TI  - Unravelling the complexity of metastasis - molecular understanding and targeted
      therapies.
AB  - Despite recognizing the devastating consequences of metastasis, we are not yet
      able to effectively treat cancer that has spread to vital organs. The inherent
      complexity of genomic alterations in late-stage cancers, coupled with numerous
      heterotypic interactions that occur between tumour and stromal cells, represent
      fundamental challenges in our quest to understand and control metastatic disease.
      The incorporation of genomic and other systems level approaches, as well as
      technological breakthroughs in imaging and animal modelling, have galvanized the
      effort to overcome gaps in our understanding of metastasis. Future research
      carries with it the potential to translate the wealth of new knowledge and
      conceptual advances into effective targeted therapies.

PMID- 21941293
TI  - Allergy: Peaceful death ends pain.

PMID- 21941294
TI  - Organ-specific features of natural killer cells.
AB  - Natural killer (NK) cells can be swiftly mobilized by danger signals and are
      among the earliest arrivals at target organs of disease. However, the role of NK
      cells in mounting inflammatory responses is often complex and sometimes
      paradoxical. Here, we examine the divergent phenotypic and functional features of
      NK cells, as deduced largely from experimental mouse models of pathophysiological
      responses in the liver, mucosal tissues, uterus, pancreas, joints and brain.
      Moreover, we discuss how organ-specific factors, the local microenvironment and
      unique cellular interactions may influence the organ-specific properties of NK
      cells.

PMID- 21941297
TI  - miRNA screening reveals a new miRNA family stimulating iPS cell generation via
      regulation of Meox2.
AB  - Induced pluripotent stem cells (iPSCs) can be generated by overexpression of
      Oct4, Sox2 and Klf4 in murine fibroblasts. By conducting a microRNA (miRNA)
      library screen, we identified a set of miRNAs critically regulating iPSC
      formation. We revealed a new miRNA family (miR-130/301/721) as an important
      regulator of iPSC induction by targeting the homeobox transcription factor Meox2
      (also known as Gax). Meox2-specific silencing mimicked the effects of this miRNA
      family on reprogramming. Mechanistically, miRNA-resistant Meox2 overexpression
      abrogated effects of miR-130/301/721 on reprogramming. In conclusion, the miRNA
      family miR-130/301/721 enhances iPSC generation via repression of Meox2.

PMID- 21941298
TI  - Lineage Commitments: Emphasis On Embryonic-Extraembryonic Interfaces.
AB  - The EMBO Workshop on 'Lineage Commitments: Emphasis on Embryonic-Extraembryonic
      Interfaces', held in May 2011, demonstrated that embryonic and extraembryonic
      tissues play early and significant interacting roles that mutually promote each
      other's further and correct deployment within the mammalian conceptus.
      Highlighted here are those presentations that directly addressed embryonic
      extraembryonic interfaces in building the mammalian fetus.

PMID- 21941295
TI  - Highlights of 10 years of immunology in Nature Reviews Immunology.
AB  - As Nature Reviews Immunology reaches its 10(th) anniversary, the authors of one
      of the top-cited articles from each year take a trip down memory lane. We've
      asked them to look back on the state of research at the time their Review was
      published, to consider why the article has had the impact it has and to discuss
      the future directions of their field. This Viewpoint article provides an
      interesting snapshot of some of the fundamental advances in immunology over the
      past 10 years. Highlights include our improved understanding of Toll-like
      receptor signalling, and of immune regulation mediated by regulatory T cells,
      indoleamine 2,3-dioxygenase, myeloid-derived suppressor cells and interleukin-10.
      The complexities in the development and heterogeneity of macrophages, dendritic
      cells and T helper cells continue to engage immunologists, as do the immune
      processes involved in diseases such as atherosclerosis. We look forward to what
      the next 10 years of immunology research may bring.

PMID- 21941296
TI  - The parallel lives of angiogenesis and immunosuppression: cancer and other tales.
AB  - Emerging evidence indicates that angiogenesis and immunosuppression frequently
      occur simultaneously in response to diverse stimuli. Here, we describe a
      fundamental biological programme that involves the activation of both
      angiogenesis and immunosuppressive responses, often through the same cell types
      or soluble factors. We suggest that the initiation of these responses is part of
      a physiological and homeostatic tissue repair programme, which can be co-opted in
      pathological states, notably by tumours. This view can help to devise new cancer
      therapies and may have implications for aseptic tissue injury, pathogen-mediated
      tissue destruction, chronic inflammation and even reproduction.

PMID- 21941299
TI  - Modulation of STIM1 and capacitative Ca2+ entry by the endoplasmic reticulum
      luminal oxidoreductase ERp57.
AB  - STIM1 is an endoplasmic reticulum (ER) membrane Ca(2+) sensor responsible for
      activation of store-operated Ca(2+) influx. We discovered that STIM1
      oligomerization and store-operated Ca(2+) entry (SOC) are modulated by the ER
      oxidoreductase ERp57. ERp57 interacts with the ER luminal domain of STIM1, with
      this interaction involving two conserved cysteine residues, C(49) and C(56). SOC
      is accelerated in the absence of ERp57 and inhibited in C(49) and C(56) mutants
      of STIM1. We show that ERp57, by ER luminal interaction with STIM1, has a
      modulatory role in capacitative Ca(2+) entry. This is the first demonstration of
      a protein involved in ER intraluminal regulation of STIM1.

PMID- 21941300
TI  - Metabolic signals regulate SIRT1 expression.

PMID- 21941301
TI  - Oral health awareness in adult patients with diabetes: a questionnaire study.
AB  - OBJECTIVE: To investigate oral health awareness, oral hygiene and attitudes
      towards general dental practitioners' (GDP) involvement in diabetes screening in
      adults with diabetes. DESIGN: Self-completion questionnaire. SETTING: General
      medical practices in Warwickshire. SUBJECTS AND METHODS: Adults with diabetes
      attending clinics run by practice or diabetes nurses in general medical
      practices. RESULTS: Two hundred and twenty-nine of 615 (37.2%) questionnaires
      were completed in 14 general medical practices. The majority of respondents
      (79.8%, 178/223) visited a dentist once or twice a year, but oral care varied;
      67.2% (133/198) reported brushing at least twice a day, whereas only 15.3%
      (29/190) flossed daily. Awareness of oral health risks was limited: 69.1%
      (150/217) had never received any oral health advice related to their diabetes.
      Over half of respondents supported the idea of dentists offering screening for
      diabetes (121/226, 53.5%). CONCLUSIONS: Many adults with diabetes have poor
      awareness of oral care and health complications associated with diabetes, and are
      receiving limited advice from healthcare professionals. Training and advice for
      both healthcare professionals and patients concerning the importance of good oral
      health in patients with diabetes is needed. The role of dentists in diabetes
      screening and support requires further investigation.

PMID- 21941302
TI  - General dental practitioners' knowledge of polymerisation of resin-based
      composite restorations and light curing unit technology.
AB  - OBJECTIVE: Clinical successful use of resin-based composite restorations (RBCs)
      depends on knowledge of material and light curing unit (LCU) related factors. The
      purpose of this study was to evaluate general dental practitioners' knowledge of
      polymerisation of RBCs and LCU technology. METHODS: Members of the Active
      Research Group of the Faculty of General Dental Practice (UK) in England,
      Scotland and Wales engaged in primary dental care were sent a letter introducing
      the study and asking for their cooperation, followed by an email containing a
      link to the online survey questionnaire, hosted on Surveymonkey.com. The
      questionnaire enquired about current LCUs, and asked a series of questions on
      material science. RESULTS: Sixty-six percent of the 274 members contacted
      responded. Fifty-seven percent used LED units, 25% quartz tungsten halogen (QTH),
      and 1% plasma arc (missing: 17%). Thirty percent reported having access to a
      radiometer. Appropriate responses regarding the degree of conversion of composite
      and adhesive materials were given by 32% and 23% respectively, and 22% agreed
      that LED and QTH LCUs had comparable efficiency in polymerising composites.
      Thirty-three percent were aware that RBCs eluted substances that may have adverse
      local or systemic consequences. Fifty-eight percent stated that if polymerisation
      of RBC is slowed down, polymerisation stress will be lower, and 43% said that
      polymerisation shrinkage will be reduced if the degree of conversion is reduced.
      Knowledge (measured by appropriate responses to these questions) was not related
      to years since qualification (r=-0.05, n=168, p=0.53). CONCLUSION: The study
      suggests that dentists' knowledge of curing RBC restorations and LCUs is poor.
      This indicates that there is a need for training and guidance in this aspect of
      primary dental care.

PMID- 21941303
TI  - A relentless pursuit.

PMID- 21941304
TI  - Not justified.

PMID- 21941305
TI  - Woeful ignorance.

PMID- 21941306
TI  - Wholly unsupportive.

PMID- 21941307
TI  - Altogether manageable.

PMID- 21941308
TI  - Upholding standards.

PMID- 21941309
TI  - Facial swellings.

PMID- 21941310
TI  - Out of touch.

PMID- 21941312
TI  - Assess your patients' anxiety.

PMID- 21941314
TI  - Fruit juice not that bad after all.

PMID- 21941315
TI  - Payment per patient for pilot practices.

PMID- 21941318
TI  - Gingival recession: Part 1. Aetiology and non-surgical management.
AB  - Gingival recession is a common finding in many patients. Some patients will not
      be concerned whereas others will have aesthetic concerns or complain of
      sensitivity. This paper highlights the aetiology of gingival recession, the
      treatment options available to treat any associated sensitivity and the non
      surgical treatment options available to restore aesthetics in patients with
      gingival recession. Subsequent papers in this series discuss the surgical
      treatment options available to correct localised recession defects.

PMID- 21941319
TI  - All-ceramic silica/glass-based crowns--clinical protocols.
AB  - The use of all-ceramic crowns offers the potential for improved aesthetic results
      compared to conventional ceramo-metal crowns. Silica/glass-based all-ceramic
      crowns are more translucent than alumina- or zirconia-based crowns and therefore
      have better optical properties. However, they are mechanically weaker and need to
      be used in conjunction with resin bonding cements. Both these aspects lead to
      increased clinical and technical demands and as such there are strict guidelines
      regarding tooth preparation and bonding procedure that need to be followed when
      using silica/glass-based all-ceramic crowns. The following article describes
      these preparation, impression and bonding guidelines with the aid of a case
      presentation.

PMID- 21941321
TI  - The policy context for skill mix in the National Health Service in the United
      Kingdom.
AB  - Workforce planning is essential if the future capacity of a state funded system
      and the supply of clinicians is to match the future need for care. Important
      aspects of this process are exploring the influences on productivity and the
      level of service that is necessary for a state funded system. Labour substitution
      has a direct impact upon the productivity of the workforce, yet the use of skill
      mix in dentistry is an area where the dental profession has lagged behind their
      medical colleagues. This brief paper explores the policy context for labour
      substitution, highlighting key barriers to its integration, potential drivers for
      change and future areas for research.

PMID- 21941326
TI  - Summary of: 'Oral health awareness in adult patients with diabetes: a
      questionnaire study'.

PMID- 21941327
TI  - Summary of: 'General dental practitioners' knowledge of polymerisation of resin
      based composite restorations and light curing unit technology'.

PMID- 21941328
TI  - An evaluation of student, patient and practitioner experience of general dental
      practice placements.
AB  - Modern undergraduate dental curricula strive to provide meaningful clinical
      experiences for their students. Outreach learning is now well established in most
      UK dental schools and provides an additional clinical environment in which the
      whole dental team can develop their skills. This paper evaluates student, patient
      and practitioner experiences of a general dental practice placement scheme. A
      number of practices in the Yorkshire region hosted senior undergraduate dental
      students. All parties were very positive about the experience. The students found
      the experience in general dental practice to be very different from that in
      outreach centres, with the experiences of working in well established teams being
      seen as very beneficial. Practitioners and their teams reported a number of
      unforeseen benefits and the patients found their experiences to be overwhelmingly
      positive. Some students reported positive perceptions of their clinical
      experience, when being interviewed for their vocational training and general
      professional training posts.

PMID- 21941358
TI  - Plaque radiotherapy treatment with ruthenium-106 for iris malignant melanoma.
AB  - PURPOSE: To report the results of ruthenium-106 plaque radiotherapy for iris
      malignant melanoma. METHODS: A retrospective study of 15 patients with pure iris
      melanoma treated with ruthenium-106 plaque radiotherapy from June 1998 to June
      2006. The main outcome measures were tumour control and ocular complications.
      RESULTS: Of the 15 patients, 8 had biopsy-proven melanoma (6 incisional and 2
      excisional biopsies). In the remaining seven patients enlargement of the lesion
      was documented. The median follow-up was 96 months (ranging from 14 months to 12
      years). Common radiation-related complications included cataract in 9 (60%)
      patients, dry eyes in 3 (20%) patients and elevated intraocular pressure in 4
      (27%) patients. Vision was preserved in 80% of patients. Local tumour control was
      obtained in all patients. CONCLUSIONS: Ruthenium-106 plaque radiotherapy is an
      effective treatment for primary malignant iris melanoma, resulting in excellent
      local control with preservation of vision. Main complications included cataract,
      dry eyes, and glaucoma.

PMID- 21941359
TI  - In-the-bag scleral suturing of intraocular lens in eyes with severe zonular
      dehiscence.
AB  - PURPOSE: To compare the degree of tilt and decentration of an intraocular lens
      (IOL), refractive status, and prediction error between eyes that underwent trans
      scleral suturing of the IOL within the capsular bag (in-the-bag scleral suturing)
      and eyes that underwent scleral suturing outside of the bag (out-of-the-bag
      scleral suturing) because of severe zonular dehiscence. PATIENTS AND METHODS:
      Thirty eyes that underwent in-the-bag scleral suturing of an IOL and 38 eyes that
      underwent out-of-the-bag scleral suturing were recruited sequentially. The tilt
      and decentration of the IOL, anterior chamber depth, manifest refractive
      spherical equivalent (MRSE), prediction error, and incidence of complications
      were examined. RESULTS: The mean tilt angle and the decentration length of the
      IOL of the in-the-bag suturing group were significantly less than those of the
      out-of-the-bag suturing group (P = 0.0003 in tilt and P = 0.0391 in
      decentration), although the anterior chamber depth was similar. The mean MRSE and
      prediction error of the in-the-bag suturing group were less than those of the out
      of-the-bag suturing group (P=0.0006 in MRSE and P = 0.0034 in error). The
      incidence of vitreous loss was less in the in-the-bag suturing group than in the
      out-of-the-bag suturing group (20% vs63.2%, P = 0.0009). CONCLUSIONS: The tilt
      and decentration of the IOL after in-the-bag scleral suturing are significantly
      less than those after out-of-the-bag scleral suturing, which may lead to less
      MRSE and less prediction error. As the incidence of vitreous loss is less after
      in-the-bag scleral suturing, in-the-bag suturing is advantageous for eyes of
      younger patients and of less complicated cases.

PMID- 21941360
TI  - Adult human buccal epithelial stem cells: identification, ex-vivo expansion, and
      transplantation for corneal surface reconstruction.
AB  - PURPOSE: To identify adult human buccal epithelial stem cells (SCs) on the basis
      of two parameters (high p63 expression and greater nucleus/cytoplasmic (N/C)
      ratio) and to evaluate clinical efficacy of ex-vivo expanded autologous
      epithelium in bilateral limbal SC-deficient (LSCD) patients. METHODS: The
      epithelial cells were isolated from buccal biopsy and cultured on human amnion in
      culture inserts with 3T3 feeder layer. The SCs were identified on the basis of
      two-parameter analysis using confocal microscopy, surface markers, and colony
      forming efficiency (CFE). The cultured epithelium was transplanted in 10 LSCD
      patients followed by penetrating keratoplasty in 4 patients. The clinical outcome
      was followed up to 3 years. RESULTS: A distinct population (3.0+/-1.7%) of small
      cells expressing high levels of p63 with greater N/C ratio was observed in buccal
      epithelium. The N/C ratio was found to be more appropriate than cell diameter for
      two-parameter analysis. These cells located in the basal layer were negative for
      connexin-43 and positive for melanoma-associated chondroitin sulfate
      proteoglycan, containing holoclones with 0.2% CFE, thus representing the SC
      population. After transplantation of cultured epithelium with increased (sixfold)
      SC content, anatomical and visual improvement was observed at 13-34 months in
      3/10 LSCD patients. CONCLUSIONS: The two-parameter SC marker is useful to
      identify and quantify buccal epithelial SCs. The transplantation of bioengineered
      SC-rich buccal epithelium is a strategy for corneal surface reconstruction in
      bilateral LSCD. However, further studies are required to optimize the culture
      conditions and to look for other sources of adult SCs for better visual outcome.

PMID- 21941361
TI  - Pilot randomised controlled trial of face-down positioning following macular hole
      surgery.
AB  - OBJECTIVE: This was a pilot randomised controlled trial (RCT) to investigate the
      effect of post-operative face-down positioning on the outcome of macular hole
      surgery and to inform the design of a larger definitive study. METHODS: In all,
      30 phakic eyes of 30 subjects with idiopathic full-thickness macular holes
      underwent vitrectomy with dye-assisted peeling of the ILM and 14%
      perfluoropropane gas. Subjects were randomly allocated to posture face down for
      10 days (posturing group) or to avoid a face-up position only (non-posturing
      group). The primary outcome was anatomical hole closure. RESULTS: Macular holes
      closed in 14 of 15 eyes (93.3%; 95% confidence interval (CI) 68-100%) in the
      posturing group and in 9 of 15 (60%; 95% CI 32-84%) in the non-posturing group.
      In a subgroup analysis of outcome according to macular hole size, all holes
      smaller than 400 MUm closed regardless of posturing (100%). In contrast, holes
      larger than 400 MUm closed in 10 of 11 eyes (91%; 95% CI 58-99%) in the posturing
      group and in only 4 of 10 eyes (40%; 95% CI 12-74%) in the non-posturing group
      (Fisher's exact test P=0.02). CONCLUSION: Post-operative face-down positioning
      may improve the likelihood of macular hole closure, particularly for holes larger
      than 400 MUm. These results support the case for a RCT.

PMID- 21941362
TI  - Acute disseminated encephalomyelitis associated with optic neuritis and marked
      peri-papillary hemorrhages.

PMID- 21941363
TI  - Pilot randomised controlled trial of face-down posturing following
      phacovitrectomy for macular hole.
AB  - BACKGROUND: To gather information on the effect of postoperative face-down
      posturing following combined phacoemulsification and vitrectomy for macular hole
      surgery in order to assist in the design of a larger definitive study. METHODS:
      Thirty phakic patients with stage II-IV full-thickness macular hole had combined
      phacoemulsification and pars plana vitrectomy with internal limiting membrane
      peel and 14% perfluoropropane (C(3)F(8)) gas. At the conclusion of surgery,
      patients were randomised either to face-down posture or to no posture, for 10
      days. The primary outcome was macular hole closure. RESULTS: The macular hole was
      successfully closed in 93.8% of the face-down posture group and in all of the no
      posture group. Mean visual improvement was 0.63 (SD=0.21) logMAR units in the
      face-down group and 0.53 (SD=0.22) in the no posture patients. CONCLUSION:
      Following combined phacoemulsification and vitrectomy, postoperative face-down
      posturing appears to make little difference to the final anatomical or visual
      outcome. If we assume a success rate of 95% in the posturing arm, and that there
      is no difference between posturing and non-posturing, then 798 patients would be
      required to be 90% sure that the 95% confidence interval will exclude a
      difference of more than 5%.

PMID- 21941364
TI  - Impaired bortezomib binding to mutant beta5 subunit of the proteasome is the
      underlying basis for bortezomib resistance in leukemia cells.
AB  - Proteasome inhibition is a novel treatment for several hematological
      malignancies. However, resistance to the proteasome inhibitor bortezomib (BTZ,
      Velcade) is an emerging clinical impediment. Mutations in the beta5 subunit of
      the proteasome, the primary target of BTZ, have been associated with drug
      resistance. However, the exact mechanism by which these mutations contribute to
      BTZ resistance, is still largely unknown. Toward this end, we here developed BTZ
      resistant multiple myeloma (8226) and acute lymphoblastic leukemia (CCRF-CEM)
      cell line models by exposure to stepwise increasing concentrations of BTZ.
      Characterization of the various BTZ-resistant cells revealed upregulation of
      mutant beta5 subunit of the proteasome. These newly identified beta5-subunit
      mutations, along with previously described mutations, formed a mutation cluster
      region in the BTZ-binding pocket of the beta5 subunit, that of the S1 specificity
      pocket in particular. Moreover, we provide the first evidence that the mechanism
      underlying BTZ resistance in these tumor cells is impaired binding of BTZ to the
      mutant beta5 subunit of the proteasome. We propose that proteasome subunit
      overexpression is an essential compensatory mechanism for the impaired catalytic
      activity of these mutant proteasomes. Our findings further suggest that second
      generation proteasome inhibitors that target the alpha7 subunit of the proteasome
      can overcome this drug resistance modality.

PMID- 21941365
TI  - High rate of TNFRSF14 gene alterations related to 1p36 region in de novo
      follicular lymphoma and impact on prognosis.

PMID- 21941366
TI  - Proliferation centers in chronic lymphocytic leukemia: correlation with
      cytogenetic and clinicobiological features in consecutive patients analyzed on
      tissue microarrays.
AB  - To better define the significance of proliferation centers (PCs), the
      morphological hallmark of chronic lymphocytic leukemia (CLL), lymph node biopsies
      taken from 183 patients were submitted to histopathologic and fluorescence in
      situ hybridization (FISH) studies using a 5-probe panel on tissue microarrays.
      Seventy-five cases (40.9%) with confluent PCs were classified as 'PCs-rich' and
      108 cases (59.1%) with scattered PCs were classified as 'typical'. Complete FISH
      data were obtained in 101 cases (55.1%), 79 of which (78.2%) displayed at least
      one chromosomal aberration. The incidence of each aberration was: 13q- 36,7%,
      14q32 translocations 30.8%, 11q- 24.7%, trisomy 12 19.5% and 17p- 15.6%. Five
      cases showed extra copies of the 14q32 region. The 'PCs-rich' group was
      associated with 17p-, 14q32/IgH translocation, +12, Ki-67>30%. The median
      survival from the time of tissue biopsy for PCs-rich and typical groups was 11
      and 64 months, respectively (P=0.00001). The PCs-rich pattern was the only
      predictive factor of an inferior survival at multivariate analysis (P=0.022).
      These findings establish an association between cytogenetic profile and the
      amount of PC in CLL, and show that this histopathologic characteristic is of
      value for risk assessment in patients with clinically significant adenopathy.

PMID- 21941367
TI  - Bone morphogenetic proteins induce apoptosis in multiple myeloma cells by Smad
      dependent repression of MYC.
AB  - Bone morphogenetic proteins (BMPs) have been shown to induce apoptosis and growth
      arrest in myeloma cells. However, the molecular mechanisms behind these events
      are not known. The MYC oncogene is a master regulator of cell growth and protein
      synthesis and MYC overexpression has been proposed to be associated with the
      progression of multiple myeloma. Here, we show that BMP-induced apoptosis in
      myeloma cells is dependent on downregulation of MYC. Moreover, the results
      suggest that targeting the MYC addiction in multiple myeloma is an efficient way
      of killing a majority of primary myeloma clones. We also found that myeloma cells
      harboring immunoglobulin (IG)-MYC translocations evaded BMP-induced apoptosis,
      suggesting a novel way for myeloma cells to overcome potential tumor suppression
      by BMPs.

PMID- 21941369
TI  - The AMPK stress response pathway mediates anoikis resistance through inhibition
      of mTOR and suppression of protein synthesis.
AB  - Suppression of anoikis after detachment of cancer cells from the extracellular
      matrix is a key step during metastasis. Here we show that, after detachment,
      mouse embryonic fibroblasts (MEFs) transformed by K-Ras(V12) or ETV6-NTRK3 (EN)
      activate a transcriptional response overrepresented by genes related to
      bioenergetic stress and the AMP-activated protein kinase (AMPK) energy-sensing
      pathway. Accordingly, AMPK is activated in both transformed and non-transformed
      cells after detachment, and AMPK deficiency restores anoikis to transformed MEFs.
      However, AMPK activation represses the mTOR complex-1 (mTORC1) pathway only in
      transformed cells, suggesting a key role for AMPK-mediated mTORC1 inhibition in
      the suppression of anoikis. Consistent with this, AMPK-/- MEFs transformed by EN
      or K-Ras show sustained mTORC1 activation after detachment and fail to suppress
      anoikis. Transformed TSC1-/- MEFs, which are incapable of suppressing mTORC1,
      also undergo anoikis after detachment, which is reversed by mTORC1 inhibitors.
      Furthermore, transformed AMPK-/- and TSC1-/- MEFs both have higher total protein
      synthesis rates than wild-type controls, and translation inhibition using
      cycloheximide partially restores their anoikis resistance, indicating a mechanism
      whereby mTORC1 inhibition suppresses anoikis. Finally, breast carcinoma cell
      lines show similar detachment-induced AMPK/mTORC1 activation and restoration of
      anoikis by AMPK inhibition. Our data implicate AMPK-mediated mTORC1 inhibition
      and suppression of protein synthesis as a means for bioenergetic conservation
      during detachment, thus promoting anoikis resistance.

PMID- 21941370
TI  - Constitutive activation of JAK2 in mammary epithelium elevates Stat5 signalling,
      promotes alveologenesis and resistance to cell death, and contributes to
      tumourigenesis.
AB  - Signalling through the janus kinase (JAK)/signal transducer and activator of
      transcription (Stat) pathway is required at different stages of mammary gland
      development, and this pathway is frequently hyper-activated in cancer, including
      tumours of the breast. Stats 3, 5 and 6 have important roles in the
      differentiation and survival of mammary alveolar cells, but somewhat
      paradoxically, both Stat3 and 5 can have oncogenic activity in the mammary gland.
      Constitutive activation of JAK2 could be anticipated to result in hyper
      activation of Stats 1, 3, 5 and 6 with concomitant cell transformation, although
      the outcome is difficult to envisage, particularly since Stats 3 and 5 play
      opposing roles in normal mammary gland development. Here, we show that expression
      of a constitutively active JAK2 mutant, JAK2 V617F, leads to hyper-activation of
      Stat5 in mammary epithelial cells (MECs), and transgenic mice expressing JAK2
      V617F specifically in the mammary gland exhibit accelerated alveologenesis during
      pregnancy and delayed post-lactational regression. Overexpressing JAK2 V617F in
      MECs in vitro results in elevated proliferation and resistance to cell death.
      Furthermore, constitutively active JAK2 enhances anchorage-independent cell
      growth in the presence of a co-operating oncogene and accelerates tumourigenesis
      in a xenograft model. Taken together, our results provide insights into
      signalling downstream of constitutively active JAK2 and could be important for
      understanding the molecular mechanisms of breast tumourigenesis.

PMID- 21941371
TI  - Isoform-specific palmitoylation of JNK regulates axonal development.
AB  - The c-jun N-terminal kinase (JNK) proteins are encoded by three genes (Jnk1-3),
      giving rise to 10 isoforms in the mammalian brain. The differential roles of JNK
      isoforms in neuronal cell death and development have been noticed in several
      pathological and physiological contexts. However, the mechanisms underlying the
      regulation of different JNK isoforms to fulfill their specific roles are poorly
      understood. Here, we report an isoform-specific regulation of JNK3 by
      palmitoylation, a posttranslational modification, and the involvement of JNK3
      palmitoylation in axonal development and morphogenesis. Two cysteine residues at
      the COOH-terminus of JNK3 are required for dynamic palmitoylation, which
      regulates JNK3's distribution on the actin cytoskeleton. Expression of
      palmitoylation-deficient JNK3 increases axonal branching and the motility of
      axonal filopodia in cultured hippocampal neurons. The Wnt family member Wnt7a, a
      known modulator of axonal branching and remodelling, regulates the palmitoylation
      and distribution of JNK3. Palmitoylation-deficient JNK3 mimics the effect of
      Wnt7a application on axonal branching, whereas constitutively palmitoylated JNK3
      results in reduced axonal branches and blocked Wnt7a induction. Our results
      demonstrate that protein palmitoylation is a novel mechanism for isoform-specific
      regulation of JNK3 and suggests a potential role of JNK3 palmitoylation in
      modulating axonal branching.

PMID- 21941372
TI  - Biological functions of p53 isoforms through evolution: lessons from animal and
      cellular models.
AB  - The TP53 tumour-suppressor gene is expressed as several protein isoforms
      generated by different mechanisms, including use of alternative promoters,
      splicing sites and translational initiation sites, that are conserved through
      evolution and within the TP53 homologues, TP63 and TP73. Although first described
      in the eighties, the importance of p53 isoforms in regulating the suppressive
      functions of p53 has only become evident in the last 10 years, by analogy with
      observations that p63 and p73 isoforms appeared indispensable to fully understand
      the biological functions of TP63 and TP73. This review summarizes recent advances
      in the field of 'p53 isoforms', including new data on p63 and p73 isoforms.
      Details of the alternative mechanisms that produce p53 isoforms and cis- and
      trans-regulators identified are provided. The main focus is on their biological
      functions (apoptosis, cell cycle, aging and so on) in cellular and animal models,
      including mouse, zebrafish and Drosophila. Finally, the deregulation of p53
      isoform expression in human cancers is reviewed. Based on these latest results,
      several developments are expected in the future: the identification of drugs
      modulating p53 isoform expression; the generation of animal models and the
      evaluation of the use of p53 isoform as biomarkers in human cancers.

PMID- 21941373
TI  - Cell-surface galectin-3 confers resistance to TRAIL by impeding trafficking of
      death receptors in metastatic colon adenocarcinoma cells.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis
      and preferentially kills tumor cells by engaging specific glycosylated death
      receptors, resulting in the internalization of ligand/receptor complexes and
      recruitment of the initiator caspase-8 to an activation platform known as the
      death-inducing signaling complex (DISC). However, emergence of TRAIL-resistant
      sub-populations may contribute to therapeutic failure. To investigate resistance
      mechanisms, we isolated a stable TRAIL-resistant sub-population of the metastatic
      colon cancer cell line LS-LIM6, designated LIM6-TR. LIM6-TR cells are impaired in
      endocytosis of TRAIL/death receptors complexes and failed to recruit/activate
      caspase-8 to the DISC upon TRAIL stimulation. Differential activation of Wnt and
      JNK pathways is not responsible for acquisition of TRAIL resistance. LIM6-TR
      cells display a marked increase in cell-surface expression of galectin-3, an
      endogenous lectin, which co-localizes with and binds death receptors. Silencing
      of galectin-3 restores TRAIL sensitivity and promotes TRAIL-mediated endocytosis
      of TRAIL/death receptors complexes. Inhibitors of galectin-3 and glycosylation
      also re-sensitize LIM6-TR to TRAIL and restore internalization of
      ligand/receptors complexes. These studies identify a novel TRAIL-resistance
      mechanism in which galectin-3 impedes trafficking of death receptor by anchoring
      them in glycan nano-clusters, blocking the execution of the apoptosis signal.

PMID- 21941374
TI  - Interstitial Lung Disease in Idiopathic Inflammatory Myopathy.
AB  - The lung is one of the most common extra-muscular targets in idiopathic
      inflammatory myopathies (IIM) and interstitial lung disease (ILD) is a prevalent
      and often devastating manifestation of IIM. IIM-associated ILD (IIM-ILD)
      contributes to nearly 80% of the mortality in IIM with a reported prevalence of
      65% of newly diagnosed IIM cases. Although ILD frequently accompanies clinical
      and laboratory findings of myositis, overt signs of muscle disease may be absent
      in the setting of significant lung disease. Understanding the varied scope of
      presentation of these diseases is essential to providing optimal patient care.
      This review will provide an in depth examination of ILD in IIM both from a
      rheumatologic and pulmonary perspective and will discuss the scope of disease,
      presenting features, genetic associations, pathogenesis, diagnosis, radiographic
      and histopathologic findings, along with biomarker assessment and a rationale for
      therapeutic intervention.

PMID- 21941375
TI  - Framework for the Statistical Shape Analysis of Brain Structures using SPHARM
      PDM.
AB  - Shape analysis has become of increasing interest to the neuroimaging community
      due to its potential to precisely locate morphological changes between healthy
      and pathological structures. This manuscript presents a comprehensive set of
      tools for the computation of 3D structural statistical shape analysis. It has
      been applied in several studies on brain morphometry, but can potentially be
      employed in other 3D shape problems. Its main limitations is the necessity of
      spherical topology.The input of the proposed shape analysis is a set of binary
      segmentation of a single brain structure, such as the hippocampus or caudate.
      These segmentations are converted into a corresponding spherical harmonic
      description (SPHARM), which is then sampled into a triangulated surfaces (SPHARM
      PDM). After alignment, differences between groups of surfaces are computed using
      the Hotelling T(2) two sample metric. Statistical p-values, both raw and
      corrected for multiple comparisons, result in significance maps. Additional
      visualization of the group tests are provided via mean difference magnitude and
      vector maps, as well as maps of the group covariance information.The correction
      for multiple comparisons is performed via two separate methods that each have a
      distinct view of the problem. The first one aims to control the family-wise error
      rate (FWER) or false-positives via the extrema histogram of non-parametric
      permutations. The second method controls the false discovery rate and results in
      a less conservative estimate of the false-negatives.

PMID- 21941376
TI  - Establishing books as conditioned reinforcers for preschool children as a
      function of an observational intervention.
AB  - We tested the effects of an observational intervention (Greer & Singer-Dudek,
      2008) on establishing children's books as conditioned reinforcers using a delayed
      multiple baseline design. Three preschool students with mild language and
      developmental delays served as the participants. Prior to the intervention, books
      did not function as reinforcers for any of the participants. The observational
      intervention consisted of a situation in which the participant observed a
      confederate being presented with access to books contingent on correct responses
      and the participant received nothing for correct responses. After several
      sessions of this treatment, the previously neutral books acquired reinforcing
      properties for maintenance and acquisition responses for all three participants.

PMID- 21941377
TI  - Transportability of equivalence-based programmed instruction: efficacy and
      efficiency in a college classroom.
AB  - College students in a psychology research-methods course learned concepts related
      to inferential statistics and hypothesis decision making. One group received
      equivalence-based instruction on conditional discriminations that were expected
      to promote the emergence of many untaught, academically useful abilities (i.e.,
      stimulus equivalence group). A negative control group received no instruction,
      and a positive (complete instruction) control group received instruction on all
      possible relations (those taught to, and emerging untaught in, the stimulus
      equivalence group). On posttests, the stimulus equivalence group performed as
      well as the positive control group (and both outperformed the negative control
      group), but those in the equivalence-based instruction condition achieved this
      outcome with significantly less training, thereby demonstrating the efficiency of
      equivalence-based instruction. Social validity measures indicated that
      participants found the instruction to be beneficial and as enjoyable as
      traditional teaching methods.

PMID- 21941378
TI  - Using differential reinforcement of low rates to reduce children's requests for
      teacher attention.
AB  - We evaluated the effectiveness of full-session differential reinforcement of low
      rates of behavior (DRL) on 3 primary school children's rates of requesting
      attention from their teacher. Using baseline rates of responding and teacher
      recommendations, we set a DRL schedule that was substantially lower than baseline
      yet still allowed the children access to teacher assistance. The DRL schedule was
      effective in reducing children's requests for assistance and approval, and the
      teacher found the intervention highly useful and acceptable. The possible
      mechanisms that account for behavior change using full-session DRL schedules are
      discussed.

PMID- 21941379
TI  - Measuring and reducing college students' procrastination.
AB  - We examined college students' procrastination when studying for weekly in-class
      quizzes. Two schedules of online practice quiz delivery were compared using a
      multiple baseline design. When online study material was made available
      noncontingently, students usually procrastinated. When access to additional study
      material was contingent on completing previous study material, studying was more
      evenly distributed. Overall, the mean gain in percentage correct scores on weekly
      in-class quizzes relative to pretests was greater during contingent access than
      during noncontingent access conditions.

PMID- 21941380
TI  - A comparison of methods for teaching receptive labeling to children with autism
      spectrum disorders.
AB  - Many early intervention curricular manuals recommend teaching auditory-visual
      conditional discriminations (i.e., receptive labeling) using the simple
      conditional method in which component simple discriminations are taught in
      isolation and in the presence of a distracter stimulus before the learner is
      required to respond conditionally. Some have argued that this procedure might be
      susceptible to faulty stimulus control such as stimulus overselectivity (Green,
      2001). Consequently, there has been a call for the use of alternative teaching
      procedures such as the conditional-only method, which involves conditional
      discrimination training from the onset of intervention. The purpose of the
      present study was to compare the simple-conditional and conditional-only methods
      for teaching receptive labeling to 3 young children diagnosed with autism
      spectrum disorders. The data indicated that the conditional-only method was a
      more reliable and efficient teaching procedure. In addition, several error
      patterns emerged during training using the simple-conditional method. The
      implications of the results with respect to current teaching practices in early
      intervention programs are discussed.

PMID- 21941381
TI  - Restricted interests and teacher presentation of items.
AB  - Restricted and repetitive behavior (RRB) is more pervasive, prevalent, frequent,
      and severe in individuals with autism spectrum disorders (ASDs) than in their
      typical peers. One subtype of RRB is restricted interests in items or activities,
      which is evident in the manner in which individuals engage with items (e.g.,
      repetitious wheel spinning), the types of items or activities they select (e.g.,
      preoccupation with a phone book), or the range of items or activities they select
      (i.e., narrow range of items). We sought to describe the relation between
      restricted interests and teacher presentation of items. Overall, we observed 5
      teachers interacting with 2 pairs of students diagnosed with an ASD. Each pair
      included 1 student with restricted interests. During these observations, teachers
      were free to present any items from an array of 4 stimuli selected by
      experimenters. We recorded student responses to teacher presentation of items and
      analyzed the data to determine the relation between teacher presentation of items
      and the consequences for presentation provided by the students. Teacher
      presentation of items corresponded with differential responses provided by
      students with ASD, and those with restricted preferences experienced a narrower
      array of items.

PMID- 21941382
TI  - Chin prompt plus re-presentation as treatment for expulsion in children with
      feeding disorders.
AB  - Expulsion (spitting out food) is a problem behavior observed in many children
      with feeding disorders. In the current investigation, we identified 4 children
      diagnosed with a feeding disorder who exhibited high rates of expulsion.
      Treatment with re-presentation (placing expelled liquids or solids back into the
      child's mouth) was not effective in reducing expulsion. Therefore, we added a
      chin-prompt procedure (the feeder applied gentle upward pressure to the child's
      chin and lower lip) for the initial presentation and the re-presentation. Chin
      prompt plus re-presentation resulted in low rates of expulsion for all 4
      children. The results are discussed in terms of the potential underlying
      mechanisms behind the effectiveness of the chin-prompt procedure.

PMID- 21941383
TI  - An evaluation of antecedent exercise on behavior maintained by automatic
      reinforcement using a three-component multiple schedule.
AB  - We evaluated antecedent exercise for treating the automatically reinforced
      problem behavior of 4 individuals with autism. We conducted preference
      assessments to identify leisure and exercise items that were associated with high
      levels of engagement and low levels of problem behavior. Next, we conducted three
      3-component multiple-schedule sequences: an antecedent-exercise test sequence, a
      noncontingent leisure-item control sequence, and a social-interaction control
      sequence. Within each sequence, we used a 3-component multiple schedule to
      evaluate preintervention, intervention, and postintervention effects. Problem
      behavior decreased during the postintervention component relative to the
      preintervention component for 3 of the 4 participants during the exercise-item
      assessment; however, the effects could not be attributed solely to exercise for 1
      of these participants.

PMID- 21941384
TI  - Examination of the influence of contingency on changes in reinforcer value.
AB  - This study examined how the amount of effort required to produce a reinforcer
      influenced subsequent preference for, and strength of, that reinforcer in 7
      individuals with intellectual disabilities. Preference assessments identified
      four moderately preferred stimuli for each participant, and progressive-ratio
      (PR) analyses indexed reinforcer strength. Stimuli were then assigned to one of
      four conditions for 4 weeks: fixed-ratio (FR) 1 schedule, escalating FR schedule,
      yoked noncontingent (NCR) delivery, and restricted access. Preference assessments
      and PR schedules were then repeated to examine changes in selection percentages
      and PR break points. Selection percentages decreased for all NCR stimuli but
      increased for most of the restricted stimuli. There were no systematic changes in
      selection percentages for either of the contingent stimuli. Break points
      increased, on average, for all conditions, but the increase was highest for the
      restricted stimuli and lowest for the NCR stimuli. These results are discussed in
      relation to recent basic research addressing the influence of effort on stimulus
      value.

PMID- 21941385
TI  - A comparison of procedural variations in teaching behavior chains: manual
      guidance, trainer completion, and no completion of untrained steps.
AB  - We compared variations for teaching a sequence of responses through forward
      chaining. Seven children who had been diagnosed with autism participated in a
      comparison of teacher completion (TC) of steps beyond the training step and
      manually guiding the student (SC) to complete steps beyond the training step. A
      no-completion (NC) condition, in which the steps beyond the training step were
      not completed, was added to the comparison with 4 of the participants. Results
      showed that learning occurred with all procedures, although 5 participants
      acquired the chains most efficiently in the SC condition and the other 2 learned
      most efficiently in the TC condition. Of the participants for whom an NC
      condition was included, the tasks were acquired with the shortest average session
      length and total training time. Despite the potential benefits of TC and SC
      procedures, NC is a viable option and may be preferable for some students.

PMID- 21941386
TI  - Calibration of observational measurement of rate of responding.
AB  - The quality of measurement systems used in almost all natural sciences other than
      behavior analysis is usually evaluated through calibration study rather than
      relying on interobserver agreement. We demonstrated some of the basic features of
      calibration using observer-measured rates of free-operant responding from 10
      scripted 10-min calibration samples on video. Five novice and 5 experienced
      observers recorded (on laptop computers) response samples with a priori
      determined response rates ranging from 0 to 8 responses per minute. Observer
      records were then compared with these predetermined reference values using linear
      regression and related graphical depiction. Results indicated that all of the
      observers recorded rates that were accurate to within +/-0.4 responses per minute
      and 5 were accurate to within +/-0.1 responses per minute, indicating that
      continuous recording of responding on computers can be highly accurate and
      precise. Additional research is recommended to investigate conditions that affect
      the quality of direct observational measurement of behavior.

PMID- 21941387
TI  - Effects of interviewer behavior on accuracy of children's responses.
AB  - Previous research has shown that certain interviewer behaviors can evoke
      inaccurate answers by children. In the current study, we examined the effects of
      approving and disapproving statements on the accuracy of 3 children's answers to
      questions in an interview (Experiment 1). We then evaluated 3 questioning
      techniques that may be used by interviewers during a forensic interview in which
      a child provides eyewitness testimony (Experiment 2). All participants responded
      with more inaccurate answers when approving statements followed inaccurate
      information and disapproving statements followed accurate information in
      Experiment 1. During Experiment 2, 1 participant responded most inaccurately when
      she was requestioned after providing an initial answer, whereas the remaining 2
      participants responded most inaccurately when the interviewer provided cowitness
      information and suggestive questions.

PMID- 21941388
TI  - Prevalence of multiply controlled problem behavior.
AB  - We examined articles in the Journal of Applied Behavior Analysis in which results
      of functional analyses indicated that problem behavior was maintained by multiple
      sources of reinforcement. Data for 88 (16.9%) of 521 subjects reported in 168
      studies met the criteria for multiple control. Data for 11 subjects (2.1%)
      involved a single response topography, whereas data for 77 subjects involved
      multiple, collapsed response topographies (14.8% of the total [521 cases] or
      87.5% of the multiple control cases), suggesting that when multiple control is
      observed, it often may be a by-product of response aggregation during assessment.

PMID- 21941389
TI  - Effects of general-case training, instructions, rehearsal, and feedback on the
      reduction of sight-reading errors by competent musicians.
AB  - We used general-case training, instructions, rehearsal, and feedback to teach 3
      advanced flute students to improve their sight-reading skills. Training resulted
      in systematic decreases in note errors, rhythm errors, repetitions, and
      hesitations for each participant. The procedures and outcomes were socially
      validated through subjective evaluation by the participants and music teachers
      not involved with the study.

PMID- 21941390
TI  - An evaluation of the good behavior game in kindergarten classrooms.
AB  - The good behavior game (GBG) is a classwide group contingency that involves
      dividing the class into two teams, creating simple rules, and arranging
      contingencies for breaking or following those rules. Five kindergarten teachers
      and classrooms participated in this evaluation of the GBG. Disruptive behavior
      markedly decreased in all five classrooms as a result of the intervention. This
      study extends the GBG literature by systematically replicating the effects of the
      GBG with the youngest group of students to date.

PMID- 21941391
TI  - A parametric analysis of errors of commission during discrete-trial training.
AB  - We investigated the effects of systematic changes in levels of treatment
      integrity by altering errors of commission during error-correction procedures as
      part of discrete-trial training. We taught 3 students with autism receptive
      nonsense shapes under 3 treatment integrity conditions (0%, 50%, or 100% errors
      of commission). Participants exhibited higher levels of performance during
      perfect implementation (0% errors). For 2 of the 3 participants, performance was
      low and showed no differentiation in the remaining conditions. Findings suggest
      that 50% commission errors may be as detrimental as 100% commission errors on
      teaching outcomes.

PMID- 21941393
TI  - Using a flipped spoon to decrease packing in children with feeding disorders.
AB  - We evaluated the effects of redistribution and swallow facilitation with a
      flipped spoon on packing in 2 children with a feeding disorder. For both
      participants, packing decreased when we implemented the flipped spoon treatment
      package. Mechanisms responsible for behavior change and areas of future research
      are discussed.

PMID- 21941394
TI  - Behavioral intervention to treat selective mutism across multiple social
      situations and community settings.
AB  - We evaluated a behavioral intervention for a 9-year-old girl with selective
      mutism. The intervention consisted of role play and video self-modeling. The
      frequency of spoken initiations, responses to questions, and communication
      breakdowns was measured during three social situations (i.e., ordering in a
      restaurant, meeting new adults, and playing with new children) and in three
      community settings. Results demonstrated increases in spoken initiations and
      responses and decreases in communication breakdowns across all situations and
      settings.

PMID- 21941395
TI  - The effects of a rectangular rapid-flashing beacon on vehicle speed.
AB  - In 2008, nearly 31% of vehicle fatalities were related to failure to adhere to
      safe vehicle speeds (National Highway Traffic Safety Administration [NHTSA],
      2009). The current study evaluated the effect of a rectangular rapid-flashing
      beacon (RRFB) triggered by excessive speed on vehicle speed using a combined
      alternating treatments and reversal design. The percentage of vehicles traveling
      above 41 mph (66 km per hour) decreased by 20%, and speed distributions showed a
      shift toward lower speeds during the RRFB condition.

PMID- 21941396
TI  - Behavioral assessment of physical activity in obese preschool children.
AB  - We measured changes in physical activity in 2 obese preschool children when a
      package intervention was evaluated in a reversal design. Physical activity was
      measured via direct observation and pedometers. Although the intervention
      produced only modest increases in activity, the results provide preliminary
      concurrent validation for the dependent measures used, in that the two measures
      covaried and a similar degree of change was observed with each across baseline
      and intervention phases.

PMID- 21941397
TI  - Improving oral reading fluency with a peer-mediated intervention.
AB  - This study examined the effects of an experimentally derived, peer-delivered
      reading intervention on the oral reading fluency of a first-grade student who had
      been referred for poor reading fluency. Same-grade peers were trained to lead the
      target student through a structured intervention protocol based on the results of
      a brief experimental analysis. Results indicated that reading improvements were
      obtained and are discussed in terms of selecting efficient interventions for use
      by peers.

PMID- 21941398
TI  - Effects of music on vocal stereotypy in children with autism.
AB  - We examined the effects of manipulating the intensity (i.e., volume) of music on
      engagement in vocal stereotypy in 2 children with autism. Noncontingent access to
      music decreased immediate engagement in vocal stereotypy for each participant,
      but it produced only marginal effects on subsequent engagement in the behavior
      (i.e., after withdrawal). Manipulating the intensity of music did not produce
      differential effects on immediate engagement in vocal stereotypy. The
      implications of the results and applications for future research are discussed.

PMID- 21941399
TI  - Reducing stimulus overselectivity through an increased observing-response
      requirement.
AB  - An adult with autism and a mild intellectual disability participated in a 0-s
      delayed matching-to-sample task. In each trial, two sample stimuli were presented
      together until the participant completed an observing-response requirement
      consisting of 1 or 10 mouse clicks in the baseline and experimental phases,
      respectively. One of the two sample stimuli then appeared randomly as a
      comparison stimulus (S+), along with two other comparison stimuli (S-). Higher
      levels of correct responding occurred under the larger observing-response
      requirement, and the proportion of errors related to one of the two sample
      stimuli decreased. Thus, stimulus overselectivity was reduced without requiring
      differential observing responses.

PMID- 21941400
TI  - A comparison of prompting tactics to establish intraverbals in children with
      autism.
AB  - We compared the efficacy of tact-to-intraverbal (i.e., using picture prompts) and
      echoic-to-intraverbal transfer-of-stimulus-control procedures to establish
      intraverbal responding in 3 boys (4 years old) with autism. For all 3
      participants, the picture prompts resulted in fewer trials to criterion, but both
      prompting tactics were eventually effective.

PMID- 21941401
TI  - Further evaluation of response-independent delivery of preferred stimuli and
      child compliance.
AB  - The effect of a fixed-time (FT) schedule involving the delivery of preferred
      stimuli prior to the issuance of a low-probability instruction was evaluated with
      2 young children with autism. The FT schedule was introduced according to a
      reversal design with 3 target instructions, 1 for the first child and 2 for the
      second child. Compliance increased for 2 of the 3 cases. A high-probability
      instruction sequence and guided compliance were implemented for the second
      instruction targeted for 1 child, with compliance increasing with guided
      compliance.

PMID- 21941403
TI  - The effects of prompting and reinforcement on safe behavior of bicycle and
      motorcycle riders.
AB  - A reversal design was used to evaluate the effects of vocal and written prompts
      as well as reinforcement on safe behavior (dismounting and walking bicycles or
      motorcycles on a sidewalk) on a university campus. Results indicated that an
      intervention that consisted of vocal and written prompts and reinforcement
      delivered by security guards was effective at increasing safe behavior exhibited
      by bicycle and motorcycle riders. No differences were observed between vehicle
      type or gender with regard to engagement in safe behavior.

PMID- 21941404
TI  - Effects of direct instruction on the acquisition of prepositions by students with
      intellectual disabilities.
AB  - Some students with intellectual disabilities require explicit instruction of
      language skills, including preposition use; however, little is known about
      effective ways to teach preposition use to this population. This study examined
      direct instruction (DI) to teach students to use and respond to prepositions.
      Results indicated that DI was an effective way to teach prepositions. Limitations
      and directions for future research are discussed.

PMID- 21941405
TI  - Evaluation of the immediate and subsequent effects of response interruption and
      redirection on vocal stereotypy.
AB  - We evaluated 2 3-component multiple-schedule sequences-a response interruption
      and redirection (RIRD) treatment sequence and a no-interaction control sequence
      using a multielement design. With this design, we were able to evaluate the
      immediate and subsequent effects of RIRD on 2 participants' vocal stereotypy. For
      both participants, RIRD produced an immediate decrease in vocal stereotypy and
      did not result in a subsequent increase.

PMID- 21941406
TI  - Behavior-analytic research on dementia in older adults.
AB  - It is estimated that 1 in 10 adults aged 65 years and older have been diagnosed
      with dementia, which is associated with numerous behavioral excesses and
      deficits. Despite the publication of a special section of the Journal of Applied
      Behavior Analysis (JABA) on behavioral gerontology (Iwata, 1986), there continues
      to be a paucity of behavior-analytic research with this population. This review
      compares the research published before and after the behavioral gerontology
      special section and evaluates the most recently published aging articles in JABA.

PMID- 21941408
TI  - Disturbances in the glutathione/ophthalmate redox buffer system in the woodchuck
      model of hepatitis virus-induced hepatocellular carcinoma.
AB  - Purpose. The incidence of liver tumors is rising in USA. The purpose of this
      study was to evaluate liver oxido-reductive status in the presence of chronic
      liver disease and hepatocellular carcinoma (HCC). Methods. Glutathione species
      and ophthalmate (OA) concentrations were measured by LC-MS in processed plasma
      and red blood cells (RBC) from infected Woodchuck with hepatitis virus (WHV).
      Blood samples were obtained from: (i) infected animals with tumors (WHV+/HCC+),
      (ii) infected animals without tumors (WHV+/HCC-) and (iii) healthy animals (WHC
      /HCC-). Results. The concentration of reduced glutathione (GSH) and the ratio
      GSH/GSG were lower in plasma from WHV+/HCC+ animals when compared to WHV+/HCC-
      and WHV-/HCC- (P < 0.01). In contrast, the concentration of oxidized glutathione
      (GSSG) was found to be higher in plasma from WHV+/HCC+ animals when compared to
      WHV+/HCC- and WHV-/HCC- (P < 0.01). The Glutathione species and its ratio from
      the RBC compartment were similar among all groups. OA concentration in both
      plasma and RBC was significantly higher from WHV+/HCC+ when compared to WHV+/HCC-
      and WHV-/HCC- (P < 0.01). Conclusions. Disturbances of the glutathione redox
      buffer system and higher concentrations of OA were found in the WCV+/HCC+ animal
      model. The role of these compounds as biomarkers of early tumor development in
      patients with end stage liver disease remains to be determined.

PMID- 21941409
TI  - Reactions of Acenaphthenequinone and Aceanthrenequinone with Arenes in Superacid.
AB  - The hydroxyalkylation reactions of aceanthrenequinone (6) and acenapthenequinone
      (7) with a series of arenes have been studied. In reactions with the Bronsted
      superacid CF(3)SO(3)H (triflic acid), the condensation products are formed in
      good yields (58-99%, 10 examples) with high regioselectivity. Computational
      studies were also done to examine the structures and energies of mono- and
      diprotonated species from 6 and 7. The results from the condensation reactions
      are consistent with the formation of superelectrophilic species involving
      protosolvation of carboxonium ion intermediates.

PMID- 21941411
TI  - DHA supplementation during pregnancy and lactation affects infants' cellular but
      not humoral immune response.
AB  - BACKGROUND: It is currently recommended that diet of pregnant mothers contain 200
      300 mg DHA/day. Aim. To determine whether DHA supplementation during pregnancy
      and lactation affects infants' immune response. METHODS: 60 women in >=3rd
      pregnancy studied; 30 randomly assigned to receive DHA 400 mg/day from 12th week
      gestation until 4 months postpartum. From breast-fed infants, blood obtained for
      anti-HBs antibodies, immunoglobulins, lymphocyte subset phenotyping, and
      intracellular cytokine production. RESULTS: CD4+ lymphocytes did not differ
      between groups, but CD4CD45RA/CD4 (naive cells) significantly higher in infants
      in DHA+ group. Proportion of CD4 and CD8 cells producing IFN(gamma) significantly
      lower in DHA+ group, with no differences in proportion of IL4-producing cells.
      Immunoglobulins and anti-HBs levels did not differ between groups. CONCLUSIONS:
      In infants of mothers receiving DHA supplementation, a higher percentage of CD4
      naive cells and decreased CD4 and CD8 IFN(gamma) production is compatible with
      attenuation of a proinflammatory response.

PMID- 21941410
TI  - Lipopolysaccharide inhibits the channel activity of the P2X7 receptor.
AB  - The purinergic P2X7 receptor (P2X7R) plays an important role during the immune
      response, participating in several events such as cytokine release, apoptosis,
      and necrosis. The bacterial endotoxin lipopolysaccharide (LPS) is one of the
      strongest stimuli of the immune response, and it has been shown that P2X7R
      activation can modulate LPS-induced responses. Moreover, a C-terminal binding
      site for LPS has been proposed. In order to evaluate if LPS can directly modulate
      the activity of the P2X7R, we tested several signaling pathways associated with
      P2X7R activation in HEK293 cells that do not express the TLR-4 receptor. We found
      that LPS alone was unable to induce any P2X7R-related activity, suggesting that
      the P2X7R is not directly activated by the endotoxin. On the other hand,
      preapplication of LPS inhibited ATP-induced currents, intracellular calcium
      increase, and ethidium bromide uptake and had no effect on ERK activation in
      HEK293 cells. In splenocytes-derived T-regulatory cells, in which ATP-induced
      apoptosis is driven by the P2X7R, LPS inhibited ATP-induced apoptosis.
      Altogether, these results demonstrate that LPS modulates the activity of the
      P2X7R and suggest that this effect could be of physiological relevance.

PMID- 21941412
TI  - Angiogenesis-related cytokines, RANKL, and osteoprotegerin in multiple myeloma
      patients in relation to clinical features and response to treatment.
AB  - An essential cytokine system for the osteoclast biology in multiple myeloma (MM)
      consists of the receptor of activator of NF-kappaB ligand (RANKL), its receptor
      (RANK), and the soluble decoy receptor, osteoprotegerin (OPG). Myeloma cells
      cause imbalance in OPG/RANKL interactions. We measured serum levels of OPG,
      soluble (s) RANKL, sRANKL/OPG ratio, markers of disease activity [LDH, CRP,
      interleukin-6 (IL-6), beta2-microglobulin (B2M)], and angiogenic factors
      [hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF)], in
      54 newly diagnosed MM patients and in 25 of them in plateau phase. All the above
      values were higher in MM patients compared to controls and decreased in plateau
      phase. sRANKL and RANKL/OPG were higher with advancing disease stage and skeletal
      grade. Significant correlations were found among RANKL and RANKL/OPG with HGF,
      LDH, VEGF, IL-6, and B2M. In conclusion, RANKL and OPG play significant roles in
      MM pathophysiology, as regulators of bone turnover and mediators of angiogenesis.

PMID- 21941414
TI  - How albumin administration for cirrhosis impacts on hospital albumin consumption
      and expenditure.
AB  - AIM: To assess the impact of guidelines for albumin prescription in an academic
      hospital, which is a referral center for liver diseases. METHODS: Although
      randomized trials and guidelines support albumin administration for some
      complications of cirrhosis, the high cost of albumin greatly limits its use in
      clinical practice. In 2003, a multidisciplinary panel at Sant'Orsola-Malpighi
      University Hospital (Bologna, Italy) used a literature-based consensus method to
      list all the acute and chronic conditions for which albumin is indicated as first
      or second-line treatment. Indications in hepatology included prevention of post
      paracentesis circulatory dysfunction and renal failure induced by spontaneous
      bacterial peritonitis, and treatment of hepatorenal syndrome and refractory
      ascites. Although still debated, albumin administration in refractory ascites is
      accepted by the Italian health care system. We analyzed albumin prescription and
      related costs before and after implementation of the new guidelines. RESULTS:
      While albumin consumption and costs doubled from 1998 to 2002, they dropped 20%
      after 2003, and remained stable for the following 6 years. Complications of
      cirrhosis, namely refractory ascites and paracentesis, represented the
      predominant indications, followed by major surgery, shock, enteric diseases, and
      plasmapheresis. Albumin consumption increased significantly after guideline
      implementation in the liver units, whereas it declined elsewhere in the hospital.
      Lastly, extra-protocol albumin prescription was estimated as < 10%. CONCLUSION:
      Albumin administration in cirrhosis according to international guidelines does
      not increase total hospital albumin consumption if its use in settings without
      evidence of efficacy is avoided.

PMID- 21941413
TI  - Common misconceptions about 5-aminosalicylates and thiopurines in inflammatory
      bowel disease.
AB  - Misconceptions are common in the care of patients with inflammatory bowel disease
      (IBD). In this paper, we state the most commonly found misconceptions in clinical
      practice and deal with the use of 5-aminosalicylates and thiopurines, to review
      the related scientific evidence, and make appropriate recommendations. Prevention
      of errors needs knowledge to avoid making such errors through ignorance. However,
      the amount of knowledge is increasing so quickly that one new danger is an
      overabundance of information. IBD is a model of a very complex disease and our
      goal with this review is to summarize the key evidence for the most common daily
      clinical problems. With regard to the use of 5-aminosalicylates, the best
      practice may to be consider abandoning the use of these drugs in patients with
      small bowel Crohn' s disease. The combined approach with oral plus topical 5
      aminosalicylates should be the first-line therapy in patients with active
      ulcerative colitis; once-daily treatment should be offered as a first choice
      regimen due to its better compliance and higher efficacy. With regard to
      thiopurines, they seem to be as effective in ulcerative colitis as in Crohn' s
      disease. Underdosing of thiopurines is a form of undertreatment. Thiopurines
      should probably be continued indefinitely because their withdrawal is associated
      with a high risk of relapse. Mercaptopurine is a safe alternative in patients
      with digestive intolerance or hepatotoxicity due to azathioprine. Finally,
      thiopurine methyltransferase (TPMT) screening cannot substitute for regular
      monitoring because the majority of cases of myelotoxicity are not TPMT-related.

PMID- 21941416
TI  - Gemcitabine in elderly patients with advanced pancreatic cancer.
AB  - AIM: To assess feasibility, tolerability and efficacy of gemcitabine-based
      chemotherapy in patients >= 75 years old with advanced pancreatic cancer.
      METHODS: All consecutive patients >= 75 years old with advanced pancreatic
      adenocarcinoma were included in this retrospective study. Necessary criteria to
      receive chemotherapy were: performance status 0-2, adequate biological parameters
      and no serious comorbidities. Other patients received best supportive care (BSC).
      RESULTS: Thirty-eight patients (53% women, median age 78 years, range 75-84) with
      pancreatic cancer (metastatic: n = 20, locally advanced: n = 18) were studied.
      Among them, 30 (79%) were able to receive chemotherapy [median number: 9
      infusions (1-45)]. Six patients (23%) had at least one episode of grade 3
      neutropenia and one patient developed a grade 3 hemolytic-uremic syndrome. No
      toxic death occurred. Three patients (11%) had a partial tumor response, 13 (46%)
      had a stable disease and 12 (43%) had a tumor progression. Median survival was
      9.1 mo (metastatic: 6.9 mo, locally advanced: 11.4 mo). CONCLUSION: Tolerance and
      efficacy of gemcitabine-based chemotherapy is acceptable in elderly patients in
      good condition, with similar results to younger patients.

PMID- 21941415
TI  - Integrin-linked kinase in gastric cancer cell attachment, invasion and tumor
      growth.
AB  - AIM: To investigate the effects of integrin-linked kinase (ILK) on gastric cancer
      cells both in vitro and in vivo. METHODS: ILK small interfering RNA (siRNA) was
      transfected into human gastric cancer BGC-823 cells and ILK expression was
      monitored by real-time quantitative polymerase chain reaction, Western blotting
      analysis and immunocytochemistry. Cell attachment, proliferation, invasion,
      microfilament dynamics and the secretion of vascular endothelial growth factor
      (VEGF) were also measured. Gastric cancer cells treated with ILK siRNA were
      subcutaneously transplanted into nude mice and tumor growth was assessed.
      RESULTS: Both ILK mRNA and protein levels were significantly down-regulated by
      ILK siRNA in human gastric cancer cells. This significantly inhibited cell
      attachment, proliferation and invasion. The knockdown of ILK also disturbed F
      actin assembly and reduced VEGF secretion in conditioned medium by 40% (P <
      0.05). Four weeks after injection of ILK siRNA-transfected gastric cancer cells
      into nude mice, tumor volume and weight were significantly reduced compared with
      that of tumors induced by cells treated with non-silencing siRNA or by untreated
      cells (P < 0.05). CONCLUSION: Targeting ILK with siRNA suppresses the growth of
      gastric cancer cells both in vitro and in vivo. ILK plays an important role in
      gastric cancer progression.

PMID- 21941417
TI  - Diagnostic efficacy of gadoxetic acid-enhanced MRI for hepatocellular carcinoma
      and dysplastic nodule.
AB  - AIM: To evaluate the relationship between the signal intensity of hepatobiliary
      phase images on gadoxetic acid-enhanced magnetic resonance imaging (MRI) and
      histological grade. METHODS: Fifty-nine patients with 82 hepatocellular lesions
      were evaluated retrospectively. Hepatobiliary phase images on gadoxetic acid
      enhanced MRI were classified into 3 groups: low, iso or high. Angiography
      assisted computed tomography (CT) findings were also classified into 3 groups: CT
      during arterial portography, and CT hepatic arteriography: A: iso, iso or low; B:
      slightly low, iso or low; and C: low, high. We correlated angiography-assisted
      CT, hepatobiliary phase findings during gadoxetic acid-enhanced MRI and
      histological grades. Furthermore, correlations between MRI findings and
      histological grade for each hemodynamic pattern were performed. Correlations
      among radiological and pathological findings were statistically evaluated using
      the chi-square test and Fisher' s exact test. RESULTS: There was a significant
      correlation between histological grade and hemodynamic pattern (P < 0.05). There
      was a significant correlation between histological grade and signal intensity in
      the hepatobiliary phase (P < 0.05) in group A lesions. There was no significant
      correlation between histological grade and signal intensity in the hepatobiliary
      phase in group B or C lesions (P > 0.05). CONCLUSION: Signal intensity in the
      hepatobiliary phase correlated with histological grade in the lesions that
      maintained portal blood flow, but did not correlate in lesions that showed
      decreased or defective portal blood flow.

PMID- 21941418
TI  - Prediction of nephrotoxicity induced by cisplatin combination chemotherapy in
      gastric cancer patients.
AB  - AIM: To evaluate the treatment options for nephrotoxicity due to cisplatin
      combination chemotherapy. METHODS: We retrospectively reviewed patients who had
      received cisplatin combination chemotherapy for gastric cancer between January
      2002 and December 2008. We investigated patients who had shown acute renal
      failure (ARF), and examined their clinical characteristics, laboratory data, use
      of preventive measures, treatment cycles, the amount of cisplatin administered,
      recovery period, subsequent treatments, and renal status between the recovered
      and unrecovered groups. RESULTS: Forty-one of the 552 patients had serum
      creatinine (SCR) levels greater than 1.5 mg/dL. We found that pre-ARF SCR, ARF
      SCR, and ARF glomerular filtration rates were significantly associated with renal
      status post-ARF between the two groups (P = 0.008, 0.026, 0.026, respectively).
      On the receiver operating characteristic curve of these values, a 1.75 mg/dL ARF
      SCR value had 87.5% sensitivity and 84.8% specificity (P = 0.011). CONCLUSION:
      Cessation or reduction of chemotherapy should be considered for patients who have
      an elevation of SCR levels during cisplatin combination chemotherapy.

PMID- 21941419
TI  - Stomach cancer screening and preventive behaviors in relatives of gastric cancer
      patients.
AB  - AIM: To investigate gastric cancer screening and preventive behaviors among the
      relatives of patients with gastric cancer [i.e., gastric cancer relatives
      (GCRs)]. METHODS: We examined the Korean National Health and Nutrition
      Examination Survey 2005 (KNHANES III) database and compared the gastric cancer
      screening and preventive behaviors of GCRs (n = 261) with those of non-GCRs (n =
      454) and controls without a family history of cancer (n = 2842). RESULTS: The
      GCRs were more likely to undergo gastric cancer screening compared with the
      control group (39.2% vs 32.3%, adjusted odds ratio: 1.43, CI: 1.05-1.95),
      although the absolute screening rate was low. Dietary patterns and smoking rates
      did not differ significantly between the groups, and a high proportion of GCRs
      reported inappropriate dietary habits (i.e., approximately 95% consumed excessive
      sodium, 30% were deficient in vitamin C, and 85% were deficient in dietary
      fiber). CONCLUSION: The gastric cancer screening and preventive behaviors of GCRs
      have yet to be improved. To increase awareness among GCRs, systematic family
      education programs should be implemented.

PMID- 21941420
TI  - Virological response to adefovir monotherapy and the risk of adefovir resistance.
AB  - AIM: To evaluate virological response to adefovir (ADV) monotherapy and emergence
      of ADV-resistant mutations in lamivudine (LAM)-resistant chronic hepatitis B
      patients. METHODS: Seventy-seven patients with documented LAM resistance who were
      treated with 10 mg/d ADV for > 96 wk were analyzed for ADV resistance. RESULTS:
      At week 48 and 96, eight (10%) and 14 (18%) of 77 LAM-resistant patients
      developed the ADV-resistant strain (rtA181V/T and/or rtN236T mutations),
      respectively. Hepatitis B virus (HBV) DNA levels during therapy were
      significantly higher in patients who developed ADV resistance than in those who
      did not. Incidence of ADV resistance at week 96 was 11%, 8% and 6% among patients
      with complete virological response (HBV DNA level < 60 IU/mL); 0%, 5% and 19%
      among patients with partial virological response (HBV DNA level >= 60 to 2000
      IU/mL); and 32%, 34% and 33% among patients with inadequate virological response
      (HBV DNA levels > 2000 IU/mL) at week 12, week 24 and week 48, respectively. HBV
      DNA levels > 2000 IU/mL at week 24 showed best performance characteristics in
      predicting ADV resistance. CONCLUSION: Development of ADV resistance mutations
      was associated with HBV DNA levels, which could identify patients with LAM
      resistance who are likely to respond to ADV monotherapy.

PMID- 21941421
TI  - Histological origin of pseudomyxoma peritonei in Chinese women: clinicopathology
      and immunohistochemistry.
AB  - AIM: To investigate the histological origin of pseudomyxoma peritonei (PMP) in
      Chinese women. METHODS: The clinical and pathological data were reviewed for 35
      women with PMP, and specimens of the peritoneal, appendiceal and ovarian lesions
      of each patient were examined using the PV-6000 immunohistochemistry method.
      Antibodies included cytokeratin (CK)7, CK20, mucin (MUC)-1, MUC-2, carbohydrate
      antigen (CA)-125, estrogen receptor (ER), and progesterone receptor (PR).
      RESULTS: Abundant colloidal mucinous tumors were observed in the peritoneum in
      all 35 cases. Thirty-one patients had a history of appendectomy, 28 of whom had
      mucinous lesions. There was one patient with appendicitis, one whose appendix
      showed no apparent pathological changes, and one with unknown surgical pathology.
      Ovarian mucinous tumors were found in 24 patients. The tumors were bilateral in
      13 patients, on the right-side in nine, and on the left side in two. Twenty
      patients had combined appendiceal and ovarian lesions; 16 of whom had undergone
      initial surgery for appendiceal lesions. Four patients had undergone initial
      surgery for ovarian lesions, and relapse occurred in these patients at 1, 11, 32
      and 85 mo after initial surgery. Appendiceal mucinous tumors were found in each
      of these four patients. Thirty-three of the 35 patients showed peritoneal lesions
      that were positive for CK20 and MUC-2, but negative for CK7, MUC-1, CA125, ER and
      PR. The expression patterns in the appendix and the ovary were similar to those
      of the peritoneal lesions. In one of the remaining two cases, CK20, CK7 and MUC-2
      were positive, and MUC-1, CA125, ER and PR were negative. The ovaries were not
      resected. The appendix of one patient was removed at another hospital, and no
      specimen was evaluated. In the other case, the appendix appeared to be normal
      during surgery, and was not resected. Peritoneal and ovarian lesions were
      negative for CK20, MUC-2, CK7, MUC-1, CA125, ER and PR. CONCLUSION: Most PMP
      originated from the appendix. Among women with PMP, the ovarian tumors were
      implanted rather than primary. For patients with PMP, appendectomy should be
      performed routinely. The ovaries, especially the right ovaries should be
      explored.

PMID- 21941422
TI  - Propofol vs traditional sedative agents for endoscopic retrograde
      cholangiopancreatography: a meta-analysis.
AB  - AIM: To investigate the efficacy and safety of propofol sedation for endoscopic
      retrograde cholangiopancreatography (ERCP). METHODS: Databases including PubMed,
      Embase, and the Cochrane Central Register of Controlled Trials updated as of
      October 2010 were searched. Main outcome measures were ERCP procedure duration,
      recovery time, incidence of hypotension and hypoxia. RESULTS: Six trials with a
      total of 663 patients were included. The pooled mean difference in ERCP procedure
      duration between the propofol and traditional sedative agents was -8.05 (95% CI: 
      16.74 to 0.63), with no significant difference between the groups. The pooled
      mean difference in the recovery time was -18.69 (95% CI: -25.44 to -11.93), which
      showed a significant reduction with use of propofol sedation. Compared with
      traditional sedative agents, the pooled OR with propofol sedation for ERCP
      causing hypotension or hypoxia was 1.69 (95% CI: 0.82-3.50) and 0.90 (95% CI:
      0.55-1.49), respectively, which indicated no significant difference between the
      groups. CONCLUSION: Propofol sedation during ERCP leads to shorter recovery time
      without an increase of cardiopulmonary side effects. Propofol sedation can
      provide adequate sedation during ERCP.

PMID- 21941423
TI  - Contrast-enhanced multiple-phase imaging features in hepatic epithelioid
      hemangioendothelioma.
AB  - AIM: To investigate and review the contrast-enhanced multiple-phase computed
      tomography (CEMP CT) and magnetic resonance imaging (MRI) findings in patients
      with pathologically confirmed hepatic epithelioid hemangioendothelioma (HEHE).
      METHODS: Findings from imaging examinations in 8 patients (5 women and 3 men)
      with pathologically confirmed HEHE were retrospectively reviewed (CT images
      obtained from 7 patients and MR images obtained from 6 patients). The age of
      presentation varied from 27 years to 60 years (average age 39.8 years). RESULTS:
      There were two types of HEHE: multifocal type (n = 7) and diffuse type (n = 1).
      In the multifocal-type cases, there were 74 lesions on CT and 28 lesions on MRI
      with 7 lesions found with diffusion weighted imaging; 18 (24.3%) of 74 lesions on
      plain CT and 26 (92.9%) of 28 lesions on pre-contrast MRI showed the target sign.
      On CEMP CT, 28 (37.8%) of 74 lesions appeared with the target sign and a
      progressive-enhancement rim and 9 (12.2%) of 74 lesions displayed progressive
      enhancement, maintaining a state of persistent enhancement. On CEMP MRI, 27
      (96.4%) of 28 lesions appeared with the target sign with a progressive
      enhancement rim and 28 (100%) of 28 lesions displayed progressive-enhancement,
      maintaining a state of persistent enhancement. In the diffuse-type cases, an
      enlarged liver was observed with a large nodule appearing with persistent
      enhancement on CEMP CT and MRI. CONCLUSION: The most important imaging features
      of HEHE are the target sign and/or progressive enhancement with persistent
      enhancement on CEMP CT and MRI. MRI is advantageous over CT in displaying these
      imaging features.

PMID- 21941424
TI  - Simultaneous bile duct and portal venous branch ligation in two-stage
      hepatectomy.
AB  - Hepatectomy is an effective surgical treatment for multiple bilobar liver
      metastases from colon cancer; however, one of the primary obstacles to completing
      surgical resection for these cases is an insufficient volume of the future
      remnant liver, which may cause postoperative liver failure. To induce atrophy of
      the unilateral lobe and hypertrophy of the future remnant liver, procedures to
      occlude the portal vein have been conventionally used prior to major hepatectomy.
      We report a case of a 50-year-old woman in whom two-stage hepatectomy was
      performed in combination with intraoperative ligation of the portal vein and the
      bile duct of the right hepatic lobe. This procedure was designed to promote the
      atrophic effect on the right hepatic lobe more effectively than the conventional
      technique, and to the best of our knowledge, it was used for the first time in
      the present case. Despite successful induction of liver volume shift as well as
      the following procedure, the patient died of subsequent liver failure after
      developing recurrent tumors. We discuss the first case in which simultaneous
      ligation of the portal vein and the biliary system was successfully applied as
      part of the first step of two-stage hepatectomy.

PMID- 21941425
TI  - Endoscopic naso-pancreatic drainage for the treatment of pancreatic fistula
      occurring after LDLT.
AB  - Pancreatic fistula is a quite rare complication in patients who undergo living
      donor liver transplantation (LDLT). However, in the cases that show pancreatic
      fistula, the limited volume of the graft and the resultant inadequate liver
      function may complicate the management of the fistula. As a result, the
      pancreatic fistula may result in the death of the patient. We present 2 cases in
      which endoscopic treatment was effective against pancreatic fistulas that
      developed after LDLT. In case 1, a 61-year-old woman underwent LDLT for primary
      biliary cirrhosis. Because of a portal venous thrombus caused by a splenorenal
      shunt, the patient underwent portal vein reconstruction, and a splenorenal shunt
      was ligated on postoperative day (POD) 7. The main pancreatic duct was injured
      during the manipulation to achieve hemostasis, thereby necessitating open
      drainage. However, discharge of pancreatic fluid continued even after POD 300.
      Endoscopic naso-pancreatic drainage (ENPD) was performed, and this procedure
      resulted in a remarkable decrease in drain output. The refractory pancreatic
      fistula healed on day 40 after ENPD. In case 2, a 58-year-old man underwent LDLT
      for cirrhosis caused by the hepatitis C virus. When the portal vein was exposed
      during thrombectomy, the pancreatic head was injured, which led to the formation
      of a pancreatic fistula. Conservative therapy was ineffective; therefore, ENPD
      was performed. The pancreatic fistula healed on day 38 after ENPD. The findings
      in these 2 cases show that endoscopic drainage of the main pancreatic duct is a
      less invasive and effective treatment for pancreatic fistulas that develop after
      LDLT.

PMID- 21941426
TI  - The Enduring Significance of Racism: Discrimination and Delinquency Among Black
      American Youth.
AB  - Prominent explanations of the overrepresentation of Black Americans in criminal
      justice statistics focus on the effects of neighborhood concentrated
      disadvantage, racial isolation, and social disorganization. We suggest that
      perceived personal discrimination is an important but frequently neglected
      complement to these factors. We test this hypothesis with longitudinal data on
      involvement in general and violent juvenile delinquency in a sample of Black
      youth from a variety of communities in 2 states. We examine the direct effects of
      concentrated disadvantage and racial isolation and the direct and mediating
      effects of social organization, support for violence, and personal
      discrimination. Consistent with our hypothesis, perceived personal discrimination
      has notable direct effects on both general and violent delinquency and is an
      important mediator between neighborhood structural conditions and offending;
      moreover, its effects exceed those associated with neighborhood conditions.

PMID- 21941427
TI  - Endometrial histopathology in patients with laparoscopic proven salpingitis and
      HIV-1 infection.
AB  - STUDY OBJECTIVE: To identify sensitive and specific histological criteria for
      endometritis in women with laparoscopically-confirmed acute salpingitis. METHODS:
      Women, age 18-40 years of age presenting with complaints of lower abdominal pain
      <=2 weeks and no antibiotics use in past two weeks, were enrolled. They underwent
      clinical examination, screening for HIV; other sexually transmitted infections
      plus endometrial biopsy sampling for histopathology. Diagnostic laparoscopy
      confirmed the diagnosis of acute salpingitis. Controls were women undergoing
      tubal ligation and HIV-1 infected women asymptomatic for genital tract infection.
      RESULTS: Of 125 women with laparoscopically-confirmed salpingitis, 38% were HIV-1
      seropositive. Nineteen HIV-1 negative controls were recruited. For the diagnosis
      of endometritis, >=1 plasma cells (PC) and >=3 polymorphonuclear lymphocytes
      (PMN) per HPF in the endometrium had a sensitivity of 74% for HIV-1-seropositive,
      63% for HIV-1-seronegative women with a specificity of 75% and positive
      predictive value of 85% regardless of HIV-1-infection for predicting moderate to
      severe salpingitis. For HIV-1-seronegative women with mild salpingitis, >=1 PC
      and >=3 PMN had a sensitivity of 16% and a PPV of 57%. CONCLUSION: Endometrial
      histology, did not perform well as a surrogate marker for moderate to severe
      salpingitis, and failed as a surrogate marker for mild salpingitis.

PMID- 21941428
TI  - The effects of fractions from shiitake mushroom on composition and cariogenicity
      of dental plaque microcosms in an in vitro caries model.
AB  - The aim of the current study was to investigate the anticariogenic potential of
      the (sub)fractions obtained from the edible mushroom shiitake (Lentinula edodes)
      in in vitro caries model. We used a modified constant depth film fermentor (CDFF)
      with pooled saliva as the inoculum and bovine dentin as a substratum. The test
      compounds were low molecular weight fraction (MLMW) of the shiitake extract and
      subfractions 4 and 5 (SF4 and SF5) of this fraction. Chlorhexidine (CHX) and
      water served as a positive and a negative control, respectively. Dentin mineral
      loss was quantified (TMR), microbial shifts within the microcosms were determined
      (qPCR), and the acidogenicity of the microcosms was assessed (CIA). From the
      compounds tested, the SF4 of shiitake showed strong inhibiting effect on dentin
      demineralization and induced microbial shifts that could be associated with oral
      health. The acid producing potential was increased, suggesting uncoupling of the
      glycolysis of the microbiota by the exposure to SF4. In conclusion, the results
      suggest that SF4 of shiitake has an anticariogenic potential.

PMID- 21941429
TI  - Effects of fruit and vegetable low molecular mass fractions on gene expression in
      gingival cells challenged with Prevotella intermedia and Actinomyces naeslundii.
AB  - Low molecular mass (LMM) fractions obtained from extracts of raspberry, red
      chicory, and Shiitake mushrooms have been shown to be an useful source of
      specific antibacterial, antiadhesion/coaggregation, and antibiofilm agent(s) that
      might be used for protection towards caries and gingivitis. In this paper, the
      effects of such LMM fractions on human gingival KB cells exposed to the
      periodontal pathogens Prevotella intermedia and Actinomyces naeslundii were
      evaluated. Expression of cytokeratin 18 (CK18) and beta4 integrin (beta4INT)
      genes, that are involved in cell proliferation/differentiation and adhesion, and
      of the antimicrobial peptide beta2 defensin (HbetaD2) in KB cells was increased
      upon exposure to either live or heat-killed bacteria. All LMM fractions tested
      prevented or reduced the induction of gene expression by P. intermedia and A.
      naeslundii depending on the experimental conditions. Overall, the results
      suggested that LMM fractions could modulate the effects of bacteria associated
      with periodontal disease in gingival cells.

PMID- 21941430
TI  - Equal force recovery in dysferlin-deficient and wild-type muscles following
      saponin exposure.
AB  - Dysferlin plays an important role in repairing membrane damage elicited by laser
      irradiation, and dysferlin deficiency causes muscular dystrophy and associated
      cardiomyopathy. Proteins such as perforin, complement component C9, and bacteria
      derived cytolysins, as well as the natural detergent saponin, can form large
      pores on the cell membrane via complexation with cholesterol. However, it is not
      clear whether dysferlin plays a role in repairing membrane damage induced by pore
      forming reagents. In this study, we observed that dysferlin-deficient muscles
      recovered the tetanic force production to the same extent as their WT
      counterparts following a 5-min saponin exposure (50 MUg/mL). Interestingly, the
      slow soleus muscles recovered significantly better than the fast extensor
      digitorum longus (EDL) muscles. Our data suggest that dysferlin is unlikely
      involved in repairing saponin-induced membrane damage and that the slow muscle is
      more efficient than the fast muscle in repairing such damage.

PMID- 21941431
TI  - On benzofuroindole analogues as smooth muscle relaxants.
AB  - At least two laboratories have independently reported the synthesis of
      benzofuroindole compounds having potential therapeutic implications in many
      disease states including those that involve smooth muscle hyperactivity. Through
      a series of in vitro screenings, they demonstrated the efficacy (and selectivity)
      of these compounds to potentiate large conductance calcium- (Ca2+-) activated K+
      (BK(Ca)) channels, by far, the most characterized of all Ca2+-dependent K+
      channels. Interestingly, promising benzofuroindole derivatives such as compound 7
      (10H-benzo[4,5]furo[3,2-b]indole) and compound 22 (4-chloro-7-trifluoromethyl-10H
      benzo[4,5]furo[3,2-b]indole-1-carboxylic acid) both exhibited high bladder
      (versus aorta) selectivity, making them attractive alternative treatments for
      bladder overactivity. In recent reports, compound 22 (LDD175 or TBIC) also showed
      inhibition of ileum and uterine contractions, indicating multiple target tissues,
      which is not surprising as BK(Ca) channels are ubiquitously expressed in the
      animal and human tissues. In this paper, the authors discuss the value of
      benzofuroindole compounds and the challenges that need to be overcome if they
      were considered as smooth muscle relaxants.

PMID- 21941432
TI  - Transversal stiffness and beta-actin and alpha-actinin-4 content of the M. soleus
      fibers in the conditions of a 3-day reloading after 14-day gravitational
      unloading.
AB  - The aim of the work was to analyze the structural changes in different parts of
      the sarcolemma and contractile apparatus of muscle fibers by measuring their
      transversal stiffness by atomic force microscopy in a three-day reloading after a
      14-day gravity disuse, which was carried out by hind-limbs suspension. The object
      of the study was the soleus muscle of the Wistar rat. It was shown that after 14
      days of disuse, there was a reduction of transversal stiffness of all points of
      the sarcolemma and contractile apparatus. Readaptation for 3 days leads to
      complete recovery of the values of the transversal stiffness of the sarcolemma
      and to partial value recovery of the contractile apparatus. The changes in
      transversal stiffness of sarcolemma correlate with beta-actin and alpha-actinin-4
      in membrane protein fractions.

PMID- 21941433
TI  - Feasibility of treating irradiated bone with intramedullary delivered autologous
      mesenchymal stem cells.
AB  - BACKGROUND: We aimed to explore (i) the short-term retention of intramedullary
      implanted mesenchymal stem cells BMSCs and (ii) their impact on the bone blood
      flow and metabolism in a rat model of hindlimb irradiation. METHODS: Three months
      after 30 Gy irradiation, fourteen animals were referred into 2 groups: a sham
      operated group (n = 6) and a treated group (n = 8) in which 111In-labelled BMSCs
      (2 * 106 cells) were injected in irradiated tibias. Bone blood flow and
      metabolism were assessed by serial (99m)Tc-HDP scintigraphy and 1-wk cell
      retention by recordings of (99m)Tc/111In activities. RESULTS: The amount of
      intramedullary implanted BMSCs was of 70% at 2 H, 40% at 48 H, and 38% at 168 H.
      Bone blood flow and bone metabolism were significantly increased during the first
      week after cell transplantation, but these effects were found to reduce at 2-mo
      followup. Conclusion. Short-term cell retention produced concomitant enhancement
      in irradiated bone blood flow and metabolism.

PMID- 21941435
TI  - Improvement of capture compound mass spectrometry technology (CCMS) for the
      profiling of human kinases by combination with 2D LC-MS/MS.
AB  - An increasingly popular and promising field in functional proteomics is the
      isolation of proteome subsets based on small molecule-protein interactions. One
      platform approach in this field are Capture Compounds that contain a small
      molecule of interest to bind target proteins, a photo-activatable reactivity
      function to covalently trap bound proteins, and a sorting function to isolate
      captured protein conjugates from complex biological samples for direct protein
      identification by liquid chromatography/mass spectrometry (nLC-MS/MS). In this
      study we used staurosporine as a selectivity group for analysis in HepG2 cells
      derived from human liver. In the present study, we combined the functional
      isolation of kinases with different separation workflows of automated split-free
      nanoflow liquid chromatography prior to mass spectrometric analysis. Two
      different CCMS setups, CCMS technology combined with 1D LC-MS and 2D LC-MS, were
      compared regarding the total number of kinase identifications. By extending the
      chromatographic separation of the tryptic digested captured proteins from 1D LC
      linear gradients to 2D LC we were able to identify 97 kinases. This result is
      similar to the 1D LC setup we previously reported but this time 4 times less
      input material was needed. This makes CCMS of kinases an even more powerful tool
      for the proteomic profiling of this important protein family.

PMID- 21941434
TI  - Differential effect of calsequestrin ablation on structure and function of fast
      and slow skeletal muscle fibers.
AB  - We compared structure and function of EDL and Soleus muscles in adult (4-6 m)
      mice lacking both Calsequestrin (CASQ) isoforms, the main SR Ca2+-binding
      proteins. Lack of CASQ induced ultrastructural alterations in ~30% of Soleus
      fibers, but not in EDL. Twitch time parameters were prolonged in both muscles,
      although tension was not reduced. However, when stimulated for 2 sec at 100 hz,
      Soleus was able to sustain contraction, while in EDL active tension declined by
      70-80%. The results presented in this paper unmask a differential effect of
      CASQ1&2 ablation in fast versus slow fibers. CASQ is essential in EDL to provide
      large amount of Ca2+ released from the SR during tetanic stimulation. In
      contrast, Soleus deals much better with lack of CASQ because slow fibers require
      lower Ca2+ amounts and slower cycling to function properly. Nevertheless, Soleus
      suffers more severe structural damage, possibly because SR Ca2+ leak is more
      pronounced.

PMID- 21941436
TI  - Synergistic antibacterial effect between silibinin and antibiotics in oral
      bacteria.
AB  - Silibinin is a composition of the silymarin group as a hepatoprotective agent,
      and it exhibits various biological activities, including antibacterial activity.
      In this study, the antibacterial activities of silibinin were investigated in
      combination with two antimicrobial agents against oral bacteria. Silibinin was
      determined with MIC and MBC values ranging from 0.1 to 3.2 and 0.2 to 6.4 
      MUg/mL, ampicillin from 0.125 to 64 and 0.5 to 64  MUg/mL, gentamicin from 2 to
      256 and 4 to 512  MUg/mL, respectively. The ranges of MIC(50) and MIC(90) were
      0.025-0.8  MUg/mL and 0.1-3.2  MUg/mL, respectively. The antibacterial activities
      of silibinin against oral bacteria were assessed using the checkerboard and time
      kill methods to evaluate the synergistic effects of treatment with ampicillin or
      gentamicin. The results were evaluated showing that the combination effects of
      silibinin with antibiotics were synergistic (FIC index <0.5) against all tested
      oral bacteria. Furthermore, a time-kill study showed that the growth of the
      tested bacteria was completely attenuated after 2-6  h of treatment with the MBC
      of silibinin, regardless of whether it was administered alone or with ampicillin
      or gentamicin. These results suggest that silibinin combined with other
      antibiotics may be microbiologically beneficial and not antagonistic.

PMID- 21941437
TI  - Role of carglumic acid in the treatment of acute hyperammonemia due to N
      acetylglutamate synthase deficiency.
AB  - N-acetylglutamate synthase (NAGS) deficiency is a rare inborn error of metabolism
      affecting ammonia detoxification in the urea cycle. The product of NAGS is N
      acetylglutamate which is the absolutely required allosteric activator of the
      first urea cycle enzyme carbamoylphosphate synthetase 1. In defects of NAGS, the
      urea cycle function can be severely affected resulting in fatal hyperammonemia in
      neonatal patients or at any later stage in life. NAGS deficiency can be treated
      with a structural analog of N-acetylglutamate, N-carbamyl-L-glutamate, which is
      available for enteral use as a licensed drug. Since NAGS deficiency is an
      extremely rare disorder, reports on the use of N-carbamyl-L-glutamate are mainly
      based on single patients. According to these, the drug is very effective in
      treating acute hyperammonemia by avoiding the need for detoxification during the
      acute metabolic decompensation. Also during long-term treatment, N-carbamyl-L
      glutamate is effective in maintaining normal plasma ammonia levels and avoiding
      the need for additional drug therapy or protein-restricted diet. Open questions
      remain which concern the optimal dosage in acute and long-term use of N-carbamyl
      L-glutamate and potential additional disorders in which the drug might also be
      effective in treating acute hyperammonemia. This review focuses on the role of N
      carbamyl-L-glutamate for the treatment of acute hyperammonemia due to primary
      NAGS deficiency but will briefly discuss the current knowledge on the role of N
      carbamyl-L-glutamate for treatment of secondary NAGS deficiencies.

PMID- 21941438
TI  - Effect of age on semen parameters in infertile men after varicocelectomy.
AB  - BACKGROUND: The effectiveness of varicocelectomy in restoration of fertility and
      improvement of semen parameters is still controversial. The purpose of this study
      was to determine the effect of age on semen parameters following varicocelectomy
      in a group of infertile men. METHODS: Improvements in sperm count, morphology,
      and motility were studied in 67 infertile patients 4-10 months after
      varicocelectomy. RESULTS: The mean age of the patients was 30.48 +/- 7.49 years.
      Significant improvements in total sperm count, percentage normal morphology, and
      motility were noted in all age groups (P < 0.05). Patients aged <25 years
      demonstrated the greatest increase in sperm counts, normal morphology, and
      motility following varicocelectomy. There was a significant negative correlation
      between age and sperm count, sperm morphology, and sperm motility (P < 0.05).
      CONCLUSION: The effect of age on improvement in sperm parameters after
      varicocelectomy is inconsistent with some reports in the literature, and could be
      attributable to the duration of infertility prior to surgery; in the long term,
      varicoceles are known to have deleterious effects on testis biology.

PMID- 21941439
TI  - Pharmacovigilance analysis of adverse event reports for aliskiren hemifumarate, a
      first-in-class direct renin inhibitor.
AB  - BACKGROUND: The purpose of this study was to examine the postmarketing safety
      profile of aliskiren hemifumarate, a first-in-class direct renin inhibitor.
      METHODS: The US Adverse Event Reporting System (AERS) was utilized to conduct a
      retrospective pharmacovigilance analysis by applying the Multi-item Gamma Poisson
      Shrinker data mining algorithm to calculate empiric Bayes geometric mean (EBGM)
      values of aliskiren-related adverse event reports. Reports received from January
      2007 through December 2008 are included in this analysis. RESULTS: In total, 1592
      reports for aliskiren are identified in the AERS. Aliskiren was associated with
      reports of angioedema (EBGM 3.9, 95% confidence interval [CI] 3.2-4.7) and renal
      dysfunction (EBGM 3.4, 95% CI 2.6-4.5). Reports of hyperkalemia, dry cough, and
      diarrhea were also linked to aliskiren (EBGM 7.4, 95% CI 3.4-13.0, EBGM 11.0, 95%
      CI 7.8-14.2, EBGM 4.3, 95% CI 3.2-5.8, respectively). CONCLUSION: Angioedema and
      renal dysfunction are potential adverse events associated with exposure to
      aliskiren. Patients with signs and symptoms of angioedema should stop aliskiren
      and seek urgent medical help. Aliskiren should not be used by patients with a
      risk of renal impairment. Additional studies are warranted to quantify further
      the risk of these events in patients with hypertension.

PMID- 21941440
TI  - Serum sodium disorders in patients with traumatic brain injury.
AB  - Sodium disorders are the most common and most poorly understood electrolyte
      disorders in neurological patients. The aim of this study was to determine the
      incidence of sodium disorders and its association with different traumatic brain
      injuries. This prospective study was conducted in 80 patients diagnosed with
      moderate and severe traumatic brain injuries. All patients underwent cerebral
      computed tomography. Incidence of sodium disorders, presence of injuries in the
      first computed tomography after traumatic brain injury, and level of
      consciousness were analyzed. Patients that presented other potential causes of
      sodium disorders and systemic trauma were excluded from the study. The incidence
      of sodium disturbances was 45%: 20 patients presented hypernatremia and 16
      hyponatremia. Refers to all patients with sodium disturbances 53% were detected
      in the first sample. We recorded at least one measurement <125 mEq/L in 50% of
      the patients with hyponatremia. A greater incidence of sodium disorders was found
      in patients with subdural, intracerebral hematoma and with diffuse axonal injury.
      The incidence of sodium disorders among the patients with diffuse lesions was
      greater than in the group of patients with brain contusion (P = 0.022). The
      incidence of sodium disorders is higher in patients with diffuse traumatic brain
      injuries. No association was found between focal lesions and proportion of sodium
      disorders.

PMID- 21941441
TI  - Profile of ciclesonide for the maintenance treatment of asthma.
AB  - Ciclesonide is a nonhalogenated synthetic inhaled corticosteroid (ICS) that has
      been approved by the US Food and Drug Administration for the treatment of all
      severities of persistent asthma. It is available as a hydrofluroalkane
      pressurized metered-dose inhaler in two strengths, 80 mcg/activation and 160
      mcg/activation, with the recommenced dosage being two inhalations twice-daily. It
      is a prodrug that is converted in the lung to its active form, which possesses
      100-fold greater glucocorticoid-receptor-binding affinity than the parent
      compound. Its relative receptor affinity is similar to budesonide. In clinical
      studies, ciclesonide was effective in improving pulmonary function, reducing
      asthma symptoms, and reducing or eliminating the need for oral corticosteroids
      (OCSs). Patients with severe asthma dependent on OCSs and high doses of ICSs were
      able to achieve greater asthma control and reduce or even eliminate the use of
      OCSs when switched to ciclesonide. In comparison with fluticasone propionate and
      budesonide, ciclesonide was demonstrated to be at least as effective in
      maintaining pulmonary function and asthma control. In clinical trials,
      ciclesonide was well tolerated, with the majority of adverse events considered
      mild or moderate in intensity. It had low systemic bioavailability and no
      clinically significant hypothalamic-pituitary-adrenal axis suppression at
      therapeutic doses. Its safety profile establishes ciclesonide as an important
      addition to the currently available ICSs.

PMID- 21941442
TI  - The effect of a physician-targeted intervention on metoclopramide prescribing
      practice.
AB  - BACKGROUND: Metoclopramide use is associated with serious and potentially
      irreversible neurologic side effects. However, it is often used for questionable
      or unclear indications in clinical practice. OBJECTIVES: To (1) determine whether
      an intervention targeted at the prescribing physician would increase the rate of
      metoclopramide discontinuation among patients prescribed the medication for
      questionable or unclear indications; and (2) assess the durability of the
      discontinuation. STUDY DESIGN: A randomized controlled trial. SETTING: Ambulatory
      practices of a quaternary care medical center. PARTICIPANTS: Ambulatory,
      electronic medical record-utilizing clinicians of the quaternary medical center.
      INTERVENTION: A letter regarding participating clinicians' prescription(s) of
      metoclopramide for patients with questionable or unclear indications. MAIN
      OUTCOME MEASURES: The rate and the durability of metoclopramide discontinuation.
      RESULTS: Fourteen of 31 (45%) patients of intervention group clinicians and 10 of
      30 (33%) patients of nonintervention group clinicians had metoclopramide
      discontinued within 12 weeks, yielding a risk ratio for metoclopramide
      discontinuation of 1.4 (95% confidence interval [CI] 0.6-3.0) in the intervention
      versus nonintervention group. Of the 29 patients who had their metoclopramide
      discontinued during the study, 26 (90%, 95% CI 73%-98%) still had no active
      metoclopramide prescription in the subsequent 6 months. No adverse events were
      detected during the follow-up period. CONCLUSION: A physician-targeted
      intervention letter did not lead to a statistically significantly increased rate
      of metoclopramide discontinuation among patients who had questionable or unclear
      indications for the medication. Discontinuation of metoclopramide therapy for
      questionable or unclear indications was durable in most patients.

PMID- 21941443
TI  - Treatment options for refractory and difficult to treat seizures: focus on
      vigabatrin.
AB  - Complex partial seizures are often refractory to current pharmacological
      therapies. These difficult to treat seizures are typically managed using multiple
      antiepileptic drugs (AEDs). AEDs as a group are frequently associated with
      significant adverse drug effects, multiple drug interactions, and numerous
      potential clinical complications due to their individual pharmacokinetic profiles
      and unique drug properties. Recently, the approval of vigabatrin by the US Food
      and Drug Administration has necessitated that clinicians re-evaluate these risk
      benefit relationships and determine where the drug fits within the treatment
      scheme for the management of complex partial seizures. This review will
      facilitate that re-evaluation through a brief review of AEDs used in the
      treatment of complex partial seizures, followed by a focused discussion on
      vigabatrin.

PMID- 21941444
TI  - Critical appraisal of the use of alpha lipoic acid (thioctic acid) in the
      treatment of symptomatic diabetic polyneuropathy.
AB  - BACKGROUND: The most common of the neuropathies associated with diabetes
      mellitus, diabetic sensorimotor polyneuropathy (DSPN) is a syndrome of diffuse,
      length-dependent, symmetric nerve dysfunction. The condition is linked with
      substantial morbidity, frequent healthcare utilization, and compromised quality
      of life due to related discomfort. Correspondingly, antidepressants,
      anticonvulsants, and opioids are regularly prescribed with the goal of pain
      control. However, the agents rarely provide complete pain relief and fail to
      address progression of the disorder. Whereas strict blood glucose control can
      slow the onset and worsening of DSPN, near-normoglycemia is not easily
      attainable. Evidence implicating oxidative processes in the pathogenesis of DSPN
      offers one potentially important therapeutic avenue. Due to its properties as a
      potent antioxidant, alpha lipoic acid (ALA) could mitigate the development of
      DSPN and attenuate resultant symptoms and signs. Approved for treatment of DSPN
      in Germany, the agent is not more widely used due to uncertainty about its
      efficacy and reported adverse effects. Here we review the effectiveness and
      tolerability of ALA in the treatment of symptomatic DSPN. METHODS: The MEDLINE,
      EMBASE, and Cochrane Library databases were searched for English-language
      literature on the topic. Randomized, blinded studies comparing parenteral and
      oral ALA with placebo in the treatment of peripheral neuropathy in diabetic
      adults were selected. Analysis included studies with a level of evidence of at
      least 2b. RESULTS: The current appraisal summarizes data from 1160 participants
      in the ALADIN, SYDNEY, ORPIL, SYDNEY 2, and ALADIN III trials. In four of the
      studies, ALA provided significant improvement in manifestations of DSPN.
      CONCLUSION: Treatment with ALA 600 mg iv daily for 3 weeks represents a well
      tolerated and effective therapy for DSPN. An oral dose of 600 mg daily
      administered for up to 5 weeks could offer benefits in symptoms and signs of DSPN
      without significant side effects.

PMID- 21941445
TI  - Cancer patient-centered home care: a new model for health care in oncology.
AB  - Patient-centered home care is a new model of assistance, which may be integrated
      with more traditional hospital-centered care especially in selected groups of
      informed and trained patients. Patient-centered care is based on patients' needs
      rather than on prognosis, and takes into account the emotional and psychosocial
      aspects of the disease. This model may be applied to elderly patients, who
      present comorbid diseases, but it also fits with the needs of younger fit
      patients. A specialized multidisciplinary team coordinated by experienced medical
      oncologists and including pharmacists, psychologists, nurses, and social
      assistance providers should carry out home care. Other professional figures may
      be required depending on patients' needs. Every effort should be made to achieve
      optimal coordination between the health professionals and the reference hospital
      and to employ shared evidence-based guidelines, which in turn guarantee safety
      and efficacy. Comprehensive care has to be easily accessible and requires a high
      level of education and knowledge of the disease for both the patients and their
      caregivers. Patient-centered home care represents an important tool to improve
      quality of life and help cancer patients while also being cost effective.

PMID- 21941446
TI  - Spinal cord injury and its association with blunt head trauma.
AB  - BACKGROUND: Severe and moderate head injury can cause misdiagnosis of a spinal
      cord injury, leading to devastating long-term consequences. The objective of this
      study is to identify risk factors involving spine trauma and moderate-to-severe
      brain injury. METHODS: A prospective study involving 1617 patients admitted in
      the emergency unit was carried out. Of these patients, 180 with moderate or
      severe head injury were enrolled. All patients were submitted to three-view spine
      series X-ray and thin cut axial CT scans for spine trauma investigations.
      RESULTS: 112 male patients and 78 female patients, whose ages ranged from 11 to
      76 years (mean age, 34 years). The most common causes of brain trauma were
      pedestrians struck by motor vehicles (31.1%), car crashes (27.7%), and falls
      (25%). Systemic lesions were present in 80 (44.4%) patients and the most common
      were fractures, and lung and spleen injuries. 52.8% had severe and 47.2% moderate
      head trauma. Fourteen patients (7.8%) suffered spinal cord injury (12 in cervical
      spine, one in lumbar, and one thoracic spine). In elderly patients, the presence
      of associated lesions and Glasgow Coma Scale (GCS) < 9 were statistically
      significant as risk factors (P < 0.05) for spine injury. CONCLUSION: Spinal cord
      injury related to moderate and severe brain trauma usually affects the cervical
      spine. The incidence of spinal lesions and GCS < 9 points were related to greater
      incidence of spinal cord injury.

PMID- 21941447
TI  - Radioelectric asymmetric stimulation of tissues as treatment for post-traumatic
      injury symptoms.
AB  - BACKGROUND: For the past few years, treatment of contusions and associated
      symptoms, such as bruising, pain, and loss of function, has involved instrument
      based therapies, ie, lasers, electromagnetic fields, and electrical stimulation.
      In this study, tissue optimization (TO) sessions were applied using a
      radioelectric asymmetric conveyor (REAC) for the treatment of contusions and
      associated symptoms. METHODS: Six subjects were treated with 12-18 sessions of
      REAC-TO applied to a traumatized anatomical area. RESULTS: In all cases, REAC-TO
      sessions were found to be effective for the treatment of post-traumatic injuries
      involving hematomas, hemorrhagic suffusion, and loss of function. In addition,
      REAC-TO treatments represented a rapid-acting analgesic associated with
      antiedematous, anti-inflammatory, and regenerative effects. These findings are
      consistent with the results of previous studies, and confirm the capacity of REAC
      TO to provide almost immediate recovery of function in traumatized areas.
      CONCLUSION: As previously demonstrated in vitro, REAC-TO is able to promote
      regeneration and repair processes in the human body. For six subjects
      experiencing local trauma, REAC-TO was effective in speeding the healing time of
      contusion symptoms and providing recovery of function.

PMID- 21941448
TI  - Seasonal variation of vitamin D and HbA(1c) levels in patients with type 1
      diabetes mellitus in the Middle East.
AB  - INTRODUCTION: The discovery that many tissues express the vitamin D receptor and
      are able to transform the 25-hydroxyvitamin D into 1,25-dihydroxyvitamin D
      (active metabolite) has led to the hypothesis that vitamin D could have a role in
      the pathogenesis and prevention of diabetes mellitus. Accumulating evidence has
      linked vitamin D deficiency with immunological disturbance in type 1 diabetes
      mellitus. Several epidemiological studies have shown lower serum 25
      hydroxyvitamin D concentrations in diabetic individuals compared to nondiabetic
      individuals. PATIENTS AND METHODS: A total of 105 Lebanese patients with type 1
      diabetes mellitus were recruited. Levels of HbA(1c) and vitamin D were recorded
      during two phases with phase 1 being the period from June-September 2009 and
      phase 2 from January-April 2009. RESULTS: Vitamin D levels at the end of sunny
      season (phase 2), reflecting the previous sunny months, were found to be higher
      than in the early summer season (phase 1) reflecting the previous cloudy months
      season, with a mean change of 0.70 +/- 6.87 ng/mL (P = 0.029). HbA(1c) levels
      were higher in phase 2 than in phase 1 with an increase of 0.175% +/- 1.46% (P =
      0.113). CONCLUSION: Vitamin D levels were higher at the end of the sunny season
      than at the end of cloudy season. HbA(1c) was also lower (but not significantly
      so) in the early summer season (cloudy months). There was a weak correlation
      between seasonal changes of vitamin D levels and the control of blood glucose as
      monitored by HbA(1c) in a cohort of Lebanese patients with type 1 diabetes
      mellitus.

PMID- 21941449
TI  - Benefit of intravenous antibiotic therapy in patients referred for treatment of
      neurologic Lyme disease.
AB  - BACKGROUND: We have shown previously that extended intravenous antibiotic therapy
      is associated with low morbidity and no mortality in patients referred for
      treatment of neurologic Lyme disease. In this study, we evaluated the benefit of
      extended intravenous antibiotic therapy in patients with symptoms of neurologic
      Lyme disease. METHODS: Patients with significant neurologic symptoms and positive
      testing for Borrelia burgdorferi were treated with intravenous antibiotics, and
      biweekly evaluation of symptom severity was performed using a six-level ordinal
      scale. Four symptoms were selected a priori as primary outcome measures in the
      study, ie, fatigue, cognition, myalgias, and arthralgias. Patients were placed
      into five groups according to time on treatment (1-4, 5-8, 9-12, 13-24, and 25-52
      weeks), and changes in the primary symptoms as a function of time on treatment
      were analyzed using a mixed-effects proportional odds model. RESULTS: Among 158
      patients with more than one follow-up visit who were monitored for up to 1 year,
      there were on average 6.7 visits per person (median 5, range 2-24). The last
      follow-up day was on average 96 days after enrollment (median 69, range 7-354
      days), corresponding to the length of antibiotic therapy. Each primary symptom
      was significantly improved at one or more time points during the study. For
      cognition, fatigue, and myalgias, the greatest improvement occurred in patients
      on the longest courses of treatment (25-52 weeks) with odds ratios (OR) for
      improvement of 1.97 (P = 0.02), 2.22 (P < 0.01), and 2.08 (P = 0.01),
      respectively. In contrast, arthralgias were only significantly improved during
      the initial 1-4 weeks of therapy (OR: 1.57, P = 0.04), and the beneficial effect
      of longer treatment did not reach statistical significance for this symptom.
      CONCLUSION: Prolonged intravenous antibiotic therapy is associated with improved
      cognition, fatigue, and myalgias in patients referred for treatment of neurologic
      Lyme disease. Treatment for 25-52 weeks may be necessary to obtain symptomatic
      improvement in these patients.

PMID- 21941451
TI  - Hepatotoxicity due to tocilizumab and anakinra in rheumatoid arthritis: two case
      reports.
AB  - Elevation of liver enzymes in patients with rheumatoid arthritis treated with the
      biological agents, tocilizumab and anakinra, is now well documented. However,
      histological characterization of these effects and outcomes has not been defined.
      Here we report toxic liver effects in two women with rheumatoid arthritis,
      refractory to all nonbiological therapies, following treatment with anakinra and
      tocilizumab. Liver biopsy in both cases showed focal necrosis of hepatocytes as a
      hallmark of drug toxicity, along with steatosis and early fibrosis. In addition,
      the patient treated with anakinra demonstrated inflammatory changes. Tocilizumab
      was continued with no further deterioration in liver function. Withdrawal of
      anakinra led to rapid normalization of liver function. The biological agents,
      tocilizumab and anakinra, may result in significant histological hepatic changes,
      including necrosis, but despite this, the outcome appears to be good.

PMID- 21941450
TI  - Possibility of enhanced risk of retinal neovascularization in repeated blood
      donors: blood donation and retinal alteration.
AB  - Repeated blood donors manifest clinical, subclinical, and biochemical signs of
      iron deficiency anemia, have significantly higher erythropoietin and vascular
      endothelial growth factor (VEGF) concentrations, and decreased tissue oxygen
      saturation, oxygenated tissue hemoglobin, and regional cerebral oxygen
      saturation. Erythropoietin and VEGF are potent retinal angiogenic factors which
      may initiate and promote the retinal angiogenesis process independently or
      simultaneously. Increases in circulating levels of erythropoietin and VEGF are
      proportionate to the levels of hematocrit, hypoxemia, and tissue hypoxia. It is
      suggested that higher erythropoietin production following iron deficiency anemia
      induced chronic hypoxemia/ hypoxia may, hypothetically, enhance the risk of
      retinal angiogenesis and/or neovascularization, possibly by inducing hypoxia
      inducible factor-1 alpha, which consequently upregulates genes stimulating
      angiogenesis, resulting in formation of a new vasculature, possibly by modulation
      of signal transducer and activator of transcription 3 signaling in the retina.
      Implications of this hypothesis cover erythropoietin doping, chronic hypoxia, and
      hypoxemic situations, such as angiogenesis-related cardiac and pulmonary
      diseases.

PMID- 21941452
TI  - Serratia pneumonia presenting as hemoptysis in a patient with sarcoidosis: a case
      report.
AB  - INTRODUCTION: Serratia marcescens is a Gram-negative bacillus which belongs to
      the family Enterobacteriaceae. It is a facultative anaerobe and produces red
      pigment at room temperature. It naturally occurs in soil and water as well as the
      intestines, and it is responsible for nosocomial infections. There have been few
      reports about community acquired pneumonia of Serratia. CASE PRESENTATION: This
      report presents a 37-year-old man with hemoptysis, fever, and shortness of
      breath. The clinical and laboratory examinations revealed that the patient had
      pseudohemoptysis due to S. marcescens pneumonia, on an immunocompromised pattern,
      because of the coexistence of sarcoidosis (stage 1). CONCLUSION: Appropriate
      antibiotic therapy for Serratia was administered, and the patient's symptoms
      regressed. The patient is healthy and asymptomatic after 1-year follow-up. To the
      best of the authors' knowledge, this is the first reported case of a
      pseudohemoptysis in a patient with pulmonary sarcoidosis.

PMID- 21941454
TI  - Antiplatelet antibody may cause delayed transfusion-related acute lung injury.
AB  - A 61-year-old woman with lung cancer developed delayed transfusion-related acute
      lung injury (TRALI) syndrome after transfusion of plasma- and leukoreduced red
      blood cells (RBCs) for gastrointestinal bleeding due to intestinal metastasis.
      Acute lung injury (ALI) recurred 31 days after the first ALI episode. Both ALI
      episodes occurred 48 hours after transfusion. Laboratory examinations revealed
      the presence of various antileukocyte antibodies including antiplatelet antibody
      in the recipient's serum but not in the donors' serum. The authors speculate that
      antiplatelet antibodies can have an inhibitory effect in the recipient, which can
      modulate the bona fide procedure of ALI and lead to a delay in the onset of ALI.
      This case illustrates the crucial role of a recipient's platelets in the
      development of TRALI.

PMID- 21941453
TI  - Management of patients during and after exacerbations of chronic obstructive
      pulmonary disease: the role of primary care physicians.
AB  - Current treatments have failed to stem the continuing rise in health care
      resource use and fatalities associated with exacerbations of chronic obstructive
      pulmonary disease (COPD). Reduction of severity and prevention of new
      exacerbations are therefore important in disease management, especially for
      patients with frequent exacerbations. Acute exacerbation treatment includes short
      acting bronchodilators, systemic corticosteroids, and antibiotics if bacterial
      infections are present. Oxygen and/or ventilatory support may be necessary for
      life-threatening conditions. Rising health care costs have provided added impetus
      to find novel therapeutic approaches in the primary care setting to prevent and
      rapidly treat exacerbations before hospitalization is required. Proactive
      interventions may include risk reduction measures (eg, smoking cessation and
      vaccinations) to reduce triggers and supplemental pulmonary rehabilitation to
      prevent or delay exacerbation recurrence. Long-term treatment strategies should
      include individualized management, addressing coexisting nonpulmonary conditions,
      and the use of maintenance pharmacotherapies, eg, long-acting bronchodilators as
      monotherapy or in combination with inhaled corticosteroids to reduce
      exacerbations. Self-management plans that help patients recognize their symptoms
      and promptly access treatments have the potential to prevent exacerbations from
      reaching the stage that requires hospitalization.

PMID- 21941455
TI  - Pharmacological versus microvascular decompression approaches for the treatment
      of trigeminal neuralgia: clinical outcomes and direct costs.
AB  - In idiopathic trigeminal neuralgia (TN) the neuroimaging evaluation is usually
      normal, but in some cases a vascular compression of trigeminal nerve root is
      present. Although the latter condition may be referred to surgery, drug therapy
      is usually the first approach to control pain. This study compared the clinical
      outcome and direct costs of (1) a traditional treatment (carbamazepine [CBZ] in
      monotherapy [CBZ protocol]), (2) the association of gabapentin (GBP) and
      analgesic block of trigger-points with ropivacaine (ROP) (GBP+ROP protocol), and
      (3) a common TN surgery, microvascular decompression of the trigeminal nerve (MVD
      protocol). Sixty-two TN patients were randomly treated during 4 weeks (CBZ [n =
      23] and GBP+ROP [n = 17] protocols) from cases of idiopathic TN, or selected for
      MVD surgery (n = 22) due to intractable pain. Direct medical cost estimates were
      determined by the price of drugs in 2008 and the hospital costs. Pain was
      evaluated using the Numerical Rating Scale (NRS) and number of pain crises; the
      Hospital Anxiety and Depression Scale, Sickness Impact Profile, and satisfaction
      with treatment and hospital team were evaluated. Assessments were performed at
      day 0 and 6 months after the beginning of treatment. All protocols showed a
      clinical improvement of pain control at month 6. The GBP+ROP protocol was the
      least expensive treatment, whereas surgery was the most expensive. With time,
      however, GBP+ROP tended to be the most and MVD the least expensive. No sequelae
      resulted in any patient after drug therapies, while after MDV surgery several
      patients showed important side effects. Data reinforce that, (1) TN patients
      should be carefully evaluated before choosing therapy for pain control, (2)
      different pharmacological approaches are available to initiate pain control at
      low costs, and (3) criteria for surgical interventions should be clearly defined
      due to important side effects, with the initial higher costs being strongly
      reduced with time.

PMID- 21941456
TI  - Absorption and tolerability of fentanyl buccal soluble film (FBSF) in patients
      with cancer in the presence of oral mucositis.
AB  - PURPOSE: Fentanyl buccal soluble film (FBSF) consists of a small, bilayered,
      water-soluble polymer film that adheres to the buccal mucosa and rapidly delivers
      fentanyl into the systemic circulation. The purpose of this study was to evaluate
      the absorption of fentanyl from FBSF in patients with cancer, with and without
      grade 1 oral mucositis, and to assess the tolerability of FBSF in this patient
      population. PATIENTS AND METHODS: In an open-label, single-dose study, two groups
      of opioid-naive patients (ie, not receiving opioids on a regular basis) with
      cancer received a 200 MUg dose of FBSF. Patients in cohort I (n = 7) had grade 1
      mucositis, and patients in cohort II (n = 7) were age- and gender-matched
      controls without mucositis. The FBSF dose was placed on the area of mucositis in
      cohort I and on a matching location in cohort II. Blood samples were collected up
      to 4 hours after administration, and safety assessments were made throughout the
      study. RESULTS: Peak plasma concentration and area under the concentration-time
      curve from time 0 to 4 hours post-dose values of patients in the grade 1
      mucositis cohort were lower than those observed in patients without mucositis.
      There was no application site irritation reported in any patient, regardless of
      mucositis status. Mild somnolence was reported by two patients with mucositis.
      There were no deaths or serious adverse events reported in this study.
      CONCLUSION: The results of this study indicate that application of FBSF to an
      area of grade 1 mucositis does not result in increased fentanyl exposure or
      irritation of the mucosa. The 200 MUg dose of FBSF was well tolerated.

PMID- 21941457
TI  - Comparison of work-related fear-avoidance beliefs across different anatomical
      locations with musculoskeletal pain.
AB  - BACKGROUND: The influence of work-related fear-avoidance on pain and function has
      been consistently reported for patients with musculoskeletal low back pain.
      Emerging evidence suggests similar influences exist for other anatomical
      locations of musculoskeletal pain, such as the cervical spine and extremities.
      However, research is limited in comparing work-related fear-avoidance and
      associations with clinical outcomes across different anatomical locations. The
      purpose of this study was to examine the associations between work-related fear
      avoidance, gender, and clinical outcomes across four different musculoskeletal
      pain locations for patients being treated in an outpatient physical therapy
      setting. METHODS: This study was a secondary analysis of data obtained
      prospectively from a cohort of 313 participants receiving physical therapy from
      an outpatient clinic. RESULTS: No interaction was found between gender and
      anatomical location of musculoskeletal pain on work-related fear-avoidance
      scores. Work-related fear-avoidance scores were higher in the cervical group
      versus the lower extremity group; however, there were no other differences across
      anatomical locations. Work-related fear-avoidance influenced intake pain
      intensity in patients with spine pain but not extremity pain. Conversely, work
      related fear-avoidance influenced intake function for participants with extremity
      pain but not spine pain. Similar results were observed for change scores, with
      higher work-related fear-avoidance being associated with more, not less, change
      in pain and function for certain anatomical locations. CONCLUSION: These findings
      suggest that work-related fear-avoidance is similar for patients experiencing
      musculoskeletal pain. However, associations between work-related fear-avoidance
      and clinical outcomes may differ based on the anatomical location of that pain.
      Further, increased work-related fear-avoidance may not be indicative of poor
      clinical outcomes for this type of patient population.

PMID- 21941458
TI  - Measuring children's distress during burns dressing changes: literature search
      for measures appropriate for indigenous children in South Africa.
AB  - BACKGROUND: Virtual reality is consistently reported as effective in reducing
      pain and anxiety in children during burns dressing changes in recent Western
      studies. Pain scales are a commonly reported outcome measure. Virtual reality is
      persuasive for all children in distress during medical procedures, because it is
      a nonaddictive, novel, and inexpensive form of distraction which can be applied
      repeatedly with good effect. We intend to use virtual reality in South Africa for
      the many children hospitalized with severe burns from mechanisms rarely seen in
      the Western world (paraffin/kerosene stoves exploding, electrical fires,
      shack/township fires, boiling liquid spills). Many severely burnt children are
      indigenous South Africans who did not speak English, and whose illiteracy levels,
      cultures, family dynamics, and experiences of pain potentially invalidate the use
      of conventional pain scales as outcome measures. The purpose of this study was to
      identify objective measures with sound psychometric properties and strong
      clinical utility, to assess distress during burns dressing changes in
      hospitalized indigenous South African children. Choice of measures was
      constrained by the burns dressing change environment, the ethics of doing no harm
      whilst measuring distress in vulnerable children, and of capturing valid measures
      of distress over the entire burns dressing change procedure. METHODS: We
      conducted two targeted systematic reviews of the literature. All major library
      databases were searched, and measures with strong psychometric properties and
      sound clinical utility were sought. RESULTS: Seven potentially useful measures
      were identified, ie, child's and caregivers' heart rate, which was measured
      continuously throughout the procedure, observed physical manifestations of
      distress using different scales (FLACCs [Face, Legs, Activity, Cry, Consolability
      Scale] and/ or Pain Behavior Checklist), time taken, and number of staff required
      to complete the procedure, and staff perspectives on the ease of use of the
      procedure. CONCLUSION: These psychometrically sound, clinically useful measures
      are alternatives to conventional pain scales, and should support valid research
      into the effectiveness of virtual reality for illiterate children with non
      Western cultures and languages.

PMID- 21941459
TI  - Current and emerging "at-site" pain medications: a review.
AB  - The myriad pain pathophysiology has intrigued and challenged humanity for
      centuries. In this regard, the traditional pain therapies such as opioids and
      nonsteroidal anti-inflammatory drugs have been highly successful in treating
      acute and chronic pain. However, their drawback includes adverse events such as
      psychotropic effects, addiction potential, and gastrointestinal toxicities, to
      mention a few. These factors combined with the likelihood of an increase in
      chronic pain conditions due to an aging population calls for the development of
      novel mechanism-based or "site-specific" agents to target novel pain pathways. In
      this regard, rapid progress has been made in understanding the molecular
      mechanisms of novel pain targets such as cannabinoid receptors, fatty acid
      hydrolase, voltage-gated and ligand-gated ion channels such as P2 receptors,
      transient receptor potential channels and glial cell modulators. Accordingly,
      preclinical studies indicate that the site-specific/selective agents exhibit
      sufficient efficacy and reduced side effects such as lack of psychotropic effects
      indicating their clinical potential. This review provides a brief summary of some
      "at-site" pain targets and their role in the pain pathophysiology, and describes
      the efforts in developing some small molecules as novel pain therapeutics.

PMID- 21941460
TI  - Widespread disulfide bonding in proteins from thermophilic archaea.
AB  - Disulfide bonds are generally not used to stabilize proteins in the cytosolic
      compartments of bacteria or eukaryotic cells, owing to the chemically reducing
      nature of those environments. In contrast, certain thermophilic archaea use
      disulfide bonding as a major mechanism for protein stabilization. Here, we
      provide a current survey of completely sequenced genomes, applying computational
      methods to estimate the use of disulfide bonding across the Archaea. Microbes
      belonging to the Crenarchaeal branch, which are essentially all
      hyperthermophilic, are universally rich in disulfide bonding while lesser degrees
      of disulfide bonding are found among the thermophilic Euryarchaea, excluding
      those that are methanogenic. The results help clarify which parts of the archaeal
      lineage are likely to yield more examples and additional specific data on protein
      disulfide bonding, as increasing genomic sequencing efforts are brought to bear.

PMID- 21941461
TI  - Establishing a markerless genetic exchange system for Methanosarcina mazei strain
      Go1 for constructing chromosomal mutants of small RNA genes.
AB  - A markerless genetic exchange system was successfully established in
      Methanosarcina mazei strain Go1 using the hpt gene coding for hypoxanthine
      phosphoribosyltransferase. First, a chromosomal deletion mutant of the hpt gene
      was generated conferring resistance to the purine analog 8-aza-2,6-diaminopurine
      (8-ADP). The nonreplicating allelic exchange vector (pRS345) carrying the pac
      resistance cassette for direct selection of chromosomal integration, and the hpt
      gene for counterselection was introduced into this strain. By a pop-in and
      ultimately pop-out event of the plasmid from the chromosome, allelic exchange is
      enabled. Using this system, we successfully generated a M. mazei deletion mutant
      of the gene encoding the regulatory non-coding RNA sRNA(154). Characterizing M.
      mazei DeltasRNA(154) under nitrogen limiting conditions demonstrated differential
      expression of at least three cytoplasmic proteins and reduced growth strongly
      arguing for a prominent role of sRNA(154) in regulation of nitrogen fixation by
      posttranscriptional regulation.

PMID- 21941462
TI  - Characterization of plasmid pPO1 from the hyperacidophile Picrophilus oshimae.
AB  - Picrophilus oshimae and Picrophilus torridus are free-living, moderately
      thermophilic and acidophilic organisms from the lineage of Euryarchaeota. With a
      pH optimum of growth at pH 0.7 and the ability to even withstand molar
      concentrations of sulphuric acid, these organisms represent the most extreme
      acidophiles known. So far, nothing is known about plasmid biology in these
      hyperacidophiles. Also, there are no genetic tools available for this genus. We
      have mobilized the 7.6 Kbp plasmid from P. oshimae in E. coli by introducing
      origin-containing transposons and described the plasmid in terms of its
      nucleotide sequence, copy number in the native host, mode of replication, and
      transcriptional start sites of the encoded ORFs. Plasmid pPO1 may encode a
      restriction/modification system in addition to its replication functions. The
      information gained from the pPO1 plasmid may prove useful in developing a cloning
      system for this group of extreme acidophiles.

PMID- 21941463
TI  - Contemporary management of renal trauma.
AB  - In the management of renal trauma, surgical exploration inevitably leads to
      nephrectomy in all but a few specialized centers. With current management
      options, the majority of hemodynamically stable patients with renal injuries can
      be successfully managed nonoperatively. Improved radiographic techniques and the
      development of a validated renal injury scoring system have led to improved
      staging of injury severity that is relatively easy to monitor. This article
      reviews a multidisciplinary approach to facilitate the care of patients with
      renal injury.

PMID- 21941464
TI  - Role of superoxide anions in the redox changes affecting the physiologically
      occurring cu(i)-glutathione complex.
AB  - The physiologically occurring copper-glutathione complex, [Cu(I)-[GSH](2)], has
      the ability to react continually with oxygen, generating superoxide anions (O(2)
      (?-)). We addressed here the effects that superoxide removal has on the redox
      state of Cu(I) and GSH present in such complex and assessed the formation of
      Cu(II)-GSSG as a final oxidation product. In addition, we investigated the
      potential of a source of O(2) (?-) external to the Cu(I)-[GSH](2) complex to
      prevent its oxidation. Removal of O(2) (?-) from a Cu(I)-[GSH](2)-containing
      solution, whether spontaneous or Tempol-induced, led to time-dependent losses in
      GSH that were greater than those affecting the metal. The losses in GSH were not
      accompanied by increments in GSSG but were largely accounted for by the
      cumulative formation of Cu(II)-GSSG molecules. Notably, the redox changes in
      Cu(I) and GSH were totally prevented when Cu(I)-[GSH](2) was coincubated with
      hypoxanthine/xanthine oxidase. Data suggest that the generation of O(2) (?-) by
      Cu(I)-[GSH](2) implies the obliged formation of an intermediate whose subsequent
      oxidation into Cu(II)-GSSG or back reduction into Cu(I)-[GSH](2) is favoured by
      either the removal or the addition of O(2) (?-), respectively.

PMID- 21941465
TI  - Emotion complexity and emotion regulation across adulthood.
AB  - This research used data from a study on daily emotional experience in adulthood
      to examine the associations between age, emotion complexity, and emotion
      regulation. Data were drawn from a study of daily stress that included 239
      participants ranging in age from 18 to 89 from North Central Florida. Two
      indicators of emotion complexity were considered: emotion differentiation and the
      co-occurrence of positive and negative affect. Emotion regulation was assessed in
      terms of individuals' likelihood of maintaining adaptive emotion states. There
      were no age differences in adults' co-occurrence of positive and negative
      emotions. In contrast to theories suggesting age would be associated with greater
      emotion complexity, the findings revealed that older adults had lower
      differentiation scores than younger adults. Age was also associated with more
      adaptive patterns of emotion regulation. Specifically, older adults persisted in
      low negative states and moved out of high negative states more readily than
      younger adults. Finally, neuroticism, self-concept incoherence, mean daily
      stress, and emotion complexity were associated with emotion regulation. Notably,
      adults who reported a greater mix of positive and negative affect moved out of
      high negative affect states more rapidly than adults with lower co-occurrence
      scores. This finding is in keeping with a growing body of work suggesting that
      positive affect promotes recovery from negative affect. Overall, the findings
      suggest that although emotion complexity is associated with emotion regulation,
      it does not appear to be a key factor underlying age differences in emotion
      regulation.

PMID- 21941466
TI  - Regulation by glycogen synthase kinase-3 of inflammation and T cells in CNS
      diseases.
AB  - Elevated markers of neuroinflammation have been found to be associated with many
      psychiatric and neurodegenerative diseases, such as mood disorders, Alzheimer's
      disease, and multiple sclerosis (MS). Since neuroinflammation is thought to
      contribute to the pathophysiology of these diseases and to impair responses to
      therapeutic interventions and recovery, it is important to identify mechanisms
      that regulate neuroinflammation and potential targets for controlling
      neuroinflammation. Recent findings have demonstrated that glycogen synthase
      kinase-3 (GSK3) is an important regulator of both the innate and adaptive immune
      systems' contributions to inflammation. Studies of the innate immune system have
      shown that inhibitors of GSK3 profoundly alter the repertoire of cytokines that
      are produced both by peripheral and central cells, reducing pro-inflammatory
      cytokines, and increasing anti-inflammatory cytokines. Furthermore, inhibitors of
      GSK3 promote tolerance to inflammatory stimuli, reducing inflammatory cytokine
      production upon repeated exposure. Studies of the adaptive immune system have
      shown that GSK3 regulates the production of cytokines by T cells and the
      differentiation of T cells to subtypes, particularly Th17 cells. Regulation of
      transcription factors by GSK3 appears to play a prominent role in its regulation
      of immune responses, including of NF-kappaB, cyclic AMP response element binding
      protein, and signal transducer and activator of transcription-3. Invivo studies
      have shown that GSK3 inhibitors ameliorate clinical symptoms of both peripheral
      and central inflammatory diseases, particularly experimental autoimmune
      encephalomyelitis, the animal model of MS. Therefore, the development and
      application of GSK3 inhibitors may provide a new therapeutic strategy to reduce
      neuroinflammation associated with many central nervous system diseases.

PMID- 21941468
TI  - Multi-neuronal recordings in the Basal Ganglia in normal and dystonic rats.
AB  - Classical rate-based pathway models are invaluable for conceptualizing
      direct/indirect basal ganglia pathways, but cannot account for many aspects of
      normal and abnormal motor control. To better understand the contribution of
      patterned basal ganglia signaling to normal and pathological motor control, we
      simultaneously recorded multi-neuronal and EMG activity in normal and dystonic
      rats. We used the jaundiced Gunn rat model of kernicterus as our experimental
      model of dystonia. Stainless steel head fixtures were implanted on the skulls and
      EMG wires were inserted into antagonistic hip muscles in nine dystonic and nine
      control rats. Under awake, head-restrained conditions, neuronal activity was
      collected from up to three microelectrodes inserted in the principal motor
      regions of the globus pallidus (GP), subthalamic nucleus, and entopeduncular
      nucleus (EP). In normal animals, most neurons discharged in regular or irregular
      patterns, without appreciable bursting. In contrast, in dystonic animals, neurons
      discharged in slow bursty or irregular, less bursty patterns. In normal rats, a
      subset of neurons showed brief discharge bursts coinciding with individual
      agonist or antagonist EMG bursts. In contrast, in dystonics, movement related
      discharges were characterized by more prolonged bursts which persist over
      multiple dystonic co-contraction epics. The pattern of movement related decreases
      in discharge activity however did not differ in dystonics compared to controls.
      In severely dystonic rats, exclusively, simultaneously recorded units often
      showed abnormally synchronized movement related pauses in GP and bursts in EP. In
      conclusion, our findings support that slow, abnormally patterned neuronal
      signaling is a fundamental pathophysiological feature of intrinsic basal ganglia
      nuclei in dystonia. Moreover, from our findings, we suggest that excessive
      movement related silencing of neuronal signaling in GP profoundly disinhibits EP
      and in turn contributes to sustained, unfocused dystonic muscle contractions.

PMID- 21941470
TI  - Parsing a perceptual decision into a sequence of moments of thought.
AB  - Theoretical, computational, and experimental studies have converged to a model of
      decision-making in which sensory evidence is stochastically integrated to a
      threshold, implementing a shift from an analog to a discrete form of computation.
      Understanding how this process can be chained and sequenced - as virtually all
      real-life tasks involve a sequence of decisions - remains an open question in
      neuroscience. We reasoned that incorporating a virtual continuum of possible
      behavioral outcomes in a simple decision task - a fundamental ingredient of real
      life decision-making - should result in a progressive sequential approximation to
      the correct response. We used real-time tracking of motor action in a decision
      task, as a measure of cognitive states reflecting an internal decision process.
      We found that response trajectories were spontaneously segmented into a discrete
      sequence of explorations separated by brief stops (about 200 ms) - which remained
      unconscious to the participants. The characteristics of these stops were
      indicative of a decision process - a "moment of thought": their duration
      correlated with the difficulty of the decision and with the efficiency of the
      subsequent exploration. Our findings suggest that simple navigation in an
      abstract space involves a discrete sequence of explorations and stops and,
      moreover, that these stops reveal a fingerprint of moments of thought.

PMID- 21941469
TI  - Timing and causality in the generation of learned eyelid responses.
AB  - The cerebellum-red nucleus-facial motoneuron (Mn) pathway has been reported as
      being involved in the proper timing of classically conditioned eyelid responses.
      This special type of associative learning serves as a model of event timing for
      studying the role of the cerebellum in dynamic motor control. Here, we have re
      analyzed the firing activities of cerebellar posterior interpositus (IP) neurons
      and orbicularis oculi (OO) Mns in alert behaving cats during classical eyeblink
      conditioning, using a delay paradigm. The aim was to revisit the hypothesis that
      the IP neurons (IPns) can be considered a neuronal phase-modulating device
      supporting OO Mns firing with an emergent timing mechanism and an explicit
      correlation code during learned eyelid movements. Optimized experimental and
      computational tools allowed us to determine the different causal relationships
      (temporal order and correlation code) during and between trials. These intra- and
      inter-trial timing strategies expanding from sub-second range (millisecond
      timing) to longer-lasting ranges (interval timing) expanded the functional domain
      of cerebellar timing beyond motor control. Interestingly, the results supported
      the above-mentioned hypothesis. The causal inferences were influenced by the
      precise motor and pre-motor spike timing in the cause-effect interval, and, in
      addition, the timing of the learned responses depended on cerebellar-Mn network
      causality. Furthermore, the timing of CRs depended upon the probability of
      simulated causal conditions in the cause-effect interval and not the mere
      duration of the inter-stimulus interval. In this work, the close relation between
      timing and causality was verified. It could thus be concluded that the firing
      activities of IPns may be related more to the proper performance of ongoing CRs
      (i.e., the proper timing as a consequence of the pertinent causality) than to
      their generation and/or initiation.

PMID- 21941471
TI  - Perceived duration of Visual and Tactile Stimuli Depends on Perceived Speed.
AB  - IT IS KNOWN THAT THE PERCEIVED DURATION OF VISUAL STIMULI IS STRONGLY INFLUENCED
      BY SPEED: faster moving stimuli appear to last longer. To test whether this is a
      general property of sensory systems we asked participants to reproduce the
      duration of visual and tactile gratings, and visuo-tactile gratings moving at a
      variable speed (3.5-15 cm/s) for three different durations (400, 600, and 800
      ms). For both modalities, the apparent duration of the stimulus increased
      strongly with stimulus speed, more so for tactile than for visual stimuli. In
      addition, visual stimuli were perceived to last approximately 200 ms longer than
      tactile stimuli. The apparent duration of visuo-tactile stimuli lay between the
      unimodal estimates, as the Bayesian account predicts, but the bimodal precision
      of the reproduction did not show the theoretical improvement. A cross-modal speed
      matching task revealed that visual stimuli were perceived to move faster than
      tactile stimuli. To test whether the large difference in the perceived duration
      of visual and tactile stimuli resulted from the difference in their perceived
      speed, we repeated the time reproduction task with visual and tactile stimuli
      matched in apparent speed. This reduced, but did not completely eliminate the
      difference in apparent duration. These results show that for both vision and
      touch, perceived duration depends on speed, pointing to common strategies of time
      perception.

PMID- 21941472
TI  - Nucleus accumbens mediates relative motivation for rewards in the absence of
      choice.
AB  - To dissociate a choice from its antecedent neural states, motivation associated
      with the expected outcome must be captured in the absence of choice. Yet, the
      neural mechanisms that mediate behavioral idiosyncrasies in motivation,
      particularly with regard to complex economic preferences, are rarely examined in
      situations without overt decisions. We employed functional magnetic resonance
      imaging in a large sample of participants while they anticipated earning rewards
      from two different modalities: monetary and candy rewards. An index for relative
      motivation toward different reward types was constructed using reaction times to
      the target for earning rewards. Activation in the nucleus accumbens (NAcc) and
      anterior insula (aINS) predicted individual variation in relative motivation
      between our reward modalities. NAcc activation, however, mediated the effects of
      aINS, indicating the NAcc is the likely source of this relative weighting. These
      results demonstrate that neural idiosyncrasies in reward efficacy exist even in
      the absence of explicit choices, and extend the role of NAcc as a critical brain
      region for such choice-free motivation.

PMID- 21941473
TI  - An integrated framework of spatiotemporal dynamics of binocular rivalry.
AB  - Fluctuations in perceptual dominance during binocular rivalry exhibit several
      hallmark characteristics. First, dominance switches are not periodic but,
      instead, stochastic: perception changes unpredictably. Second, despite being
      stochastic, average durations of rivalry dominance vary dependent on the strength
      of the rival stimuli: variations in contrast, luminance, or spatial frequency
      produce predictable changes in average dominance durations and, hence, in
      alternation rate. Third, perceptual switches originate locally and spread
      globally over time, sometimes as traveling waves of dominance: rivalry
      transitions are spatiotemporal events. This essay (1) reviews recent advances in
      our understanding of the bases of these three hallmark characteristics of
      binocular rivalry dynamics and (2) provides an integrated framework to account
      for those dynamics using cooperative and competitive spatial interactions among
      local neural circuits distributed over the visual field's retinotopic map. We
      close with speculations about how that framework might incorporate top-down
      influences on rivalry dynamics.

PMID- 21941467
TI  - Basal Ganglia disorders associated with imbalances in the striatal striosome and
      matrix compartments.
AB  - The striatum is composed principally of GABAergic, medium spiny striatal
      projection neurons (MSNs) that can be categorized based on their gene expression,
      electrophysiological profiles, and input-output circuits. Major subdivisions of
      MSN populations include (1) those in ventromedial and dorsolateral striatal
      regions, (2) those giving rise to the direct and indirect pathways, and (3) those
      that lie in the striosome and matrix compartments. The first two classificatory
      schemes have enabled advances in understanding of how basal ganglia circuits
      contribute to disease. However, despite the large number of molecules that are
      differentially expressed in the striosomes or the extra-striosomal matrix, and
      the evidence that these compartments have different input-output connections, our
      understanding of how this compartmentalization contributes to striatal function
      is still not clear. A broad view is that the matrix contains the direct and
      indirect pathway MSNs that form parts of sensorimotor and associative circuits,
      whereas striosomes contain MSNs that receive input from parts of limbic cortex
      and project directly or indirectly to the dopamine-containing neurons of the
      substantia nigra, pars compacta. Striosomes are widely distributed within the
      striatum and are thought to exert global, as well as local, influences on
      striatal processing by exchanging information with the surrounding matrix,
      including through interneurons that send processes into both compartments. It has
      been suggested that striosomes exert and maintain limbic control over behaviors
      driven by surrounding sensorimotor and associative parts of the striatal matrix.
      Consistent with this possibility, imbalances between striosome and matrix
      functions have been reported in relation to neurological disorders, including
      Huntington's disease, L-DOPA-induced dyskinesias, dystonia, and drug addiction.
      Here, we consider how signaling imbalances between the striosomes and matrix
      might relate to symptomatology in these disorders.

PMID- 21941475
TI  - Experiencing art: the influence of expertise and painting abstraction level.
AB  - How does expertise influence the perception of representational and abstract
      paintings? We asked 20 experts on art history and 20 laypersons to explore and
      evaluate a series of paintings ranging in style from representational to abstract
      in five categories. We compared subjective esthetic judgments and emotional
      evaluations, gaze patterns, and electrodermal reactivity between the two groups
      of participants. The level of abstraction affected esthetic judgments and
      emotional valence ratings of the laypersons but had no effect on the opinions of
      the experts: the laypersons' esthetic and emotional ratings were highest for
      representational paintings and lowest for abstract paintings, whereas the
      opinions of the experts were independent of the abstraction level. The gaze
      patterns of both groups changed as the level of abstraction increased: the number
      of fixations and the length of the scanpaths increased while the duration of the
      fixations decreased. The viewing strategies - reflected in the target, location,
      and path of the fixations - however indicated that experts and laypersons paid
      attention to different aspects of the paintings. The electrodermal reactivity did
      not vary according to the level of abstraction in either group but expertise was
      reflected in weaker responses, compared with laypersons, to information received
      about the paintings.

PMID- 21941474
TI  - Neural substrates of visual spatial coding and visual feedback control for hand
      movements in allocentric and target-directed tasks.
AB  - Neuropsychological evidence suggests that different brain areas may be involved
      in movements that are directed at visual targets (e.g., pointing or reaching),
      and movements that are based on allocentric visual information (e.g., drawing or
      copying). Here we used fMRI to investigate the neural correlates of these two
      types of movements in healthy volunteers. Subjects (n = 14) performed right hand
      movements in either a target-directed task (moving a cursor to a target dot) or
      an allocentric task (moving a cursor to reproduce the distance and direction
      between two distal target dots) with or without visual feedback about their hand
      movement. Movements were monitored with an MR compatible touch panel. A whole
      brain analysis revealed that movements in allocentric conditions led to an
      increase in activity in the fundus of the left intra-parietal sulcus (IPS), in
      posterior IPS, in bilateral dorsal premotor cortex (PMd), and in the lateral
      occipital complex (LOC). Visual feedback in both target-directed and allocentric
      conditions led to an increase in activity in area MT+, superior parietal
      occipital cortex (SPOC), and posterior IPS (all bilateral). In addition, we found
      that visual feedback affected brain activity differently in target-directed as
      compared to allocentric conditions, particularly in the pre-supplementary motor
      area, PMd, IPS, and parieto-occipital cortex. Our results, in combination with
      previous findings, suggest that the LOC is essential for allocentric visual
      coding and that SPOC is involved in visual feedback control. The differences in
      brain activity between target-directed and allocentric visual feedback conditions
      may be related to behavioral differences in visual feedback control. Our results
      advance the understanding of the visual coordinate frame used by the LOC. In
      addition, because of the nature of the allocentric task, our results have
      relevance for the understanding of neural substrates of magnitude estimation and
      vector coding of movements.

PMID- 21941476
TI  - How do we see art: an eye-tracker study.
AB  - We describe the pattern of fixations of subjects looking at figurative and
      abstract paintings from different artists (Molina, Mondrian, Rembrandt, della
      Francesca) and at modified versions in which different aspects of these art
      pieces were altered with simple digital manipulations. We show that the fixations
      of the subjects followed some general common principles (e.g., being attracted to
      saliency regions) but with a large variability for the figurative paintings,
      according to the subject's personal appreciation and knowledge. In particular, we
      found different gazing patterns depending on whether the subject saw the original
      or the modified version of the painting first. We conclude that the study of
      gazing patterns obtained by using the eye-tracker technology gives a useful
      approach to quantify how subjects observe art.

PMID- 21941477
TI  - A Bottom-up Approach to Data Annotation in Neurophysiology.
AB  - Metadata providing information about the stimulus, data acquisition, and
      experimental conditions are indispensable for the analysis and management of
      experimental data within a lab. However, only rarely are metadata available in a
      structured, comprehensive, and machine-readable form. This poses a severe problem
      for finding and retrieving data, both in the laboratory and on the various
      emerging public data bases. Here, we propose a simple format, the "open metaData
      Markup Language" (odML), for collecting and exchanging metadata in an automated,
      computer-based fashion. In odML arbitrary metadata information is stored as
      extended key-value pairs in a hierarchical structure. Central to odML is a clear
      separation of format and content, i.e., neither keys nor values are defined by
      the format. This makes odML flexible enough for storing all available metadata
      instantly without the necessity to submit new keys to an ontology or controlled
      terminology. Common standard keys can be defined in odML-terminologies for
      guaranteeing interoperability. We started to define such terminologies for
      neurophysiological data, but aim at a community driven extension and refinement
      of the proposed definitions. By customized terminologies that map to these
      standard terminologies, metadata can be named and organized as required or
      preferred without softening the standard. Together with the respective libraries
      provided for common programming languages, the odML format can be integrated into
      the laboratory workflow, facilitating automated collection of metadata
      information where it becomes available. The flexibility of odML also encourages a
      community driven collection and definition of terms used for annotating data in
      the neurosciences.

PMID- 21941479
TI  - Improvement of Cheilitis granulomatosa after Dental Treatment.
AB  - A 38-year-old male suffered from swelling of the lower lip for 3 months. Neither
      facial nerve palsy nor fissuring of the tongue was present. Histological
      examination of a biopsy taken from the lower lip revealed non-caseous epithelioid
      cell granulomas, suggestive of cheilitis granulomatosa. Patch testing revealed
      positive reactions to mercury chloride and amalgam. His symptoms markedly
      improved 3 months after treatment of the apical periodontitis and replacement of
      dental crowns. As his dental crowns did not contain mercury, we believe that the
      cheilitis granulomatosa may have been related to the focal dental infection.

PMID- 21941480
TI  - Preoperative Assessment Using Magnetic Resonance Imaging for Subungual Exostosis
      beneath the Proximal Region of the Nail Plate.
AB  - Subungual exostosis is a benign calcifying projection that occurs on the distal
      phalanx beneath or beside the nail. The problems in treatment are frequent
      postoperative recurrence and nail deformity or loss. Here, we describe the case
      of a male patient with a subungual exostosis beneath the proximal region of the
      nail plate of the right big toe. A precise preoperative evaluation of the
      anatomical structure using magnetic resonance imaging was useful for removing the
      subungual exostosis.

PMID- 21941478
TI  - A comprehensive metabolic profile of cultured astrocytes using isotopic transient
      metabolic flux analysis and C-labeled glucose.
AB  - Metabolic models have been used to elucidate important aspects of brain
      metabolism in recent years. This work applies for the first time the concept of
      isotopic transient 13C metabolic flux analysis (MFA) to estimate intracellular
      fluxes in primary cultures of astrocytes. This methodology comprehensively
      explores the information provided by 13C labeling time-courses of intracellular
      metabolites after administration of a 13C-labeled substrate. Cells were incubated
      with medium containing [1-13C]glucose for 24 h and samples of cell supernatant
      and extracts collected at different time points were then analyzed by mass
      spectrometry and/or high performance liquid chromatography. Metabolic fluxes were
      estimated by fitting a carbon labeling network model to isotopomer profiles
      experimentally determined. Both the fast isotopic equilibrium of glycolytic
      metabolite pools and the slow labeling dynamics of TCA cycle intermediates are
      described well by the model. The large pools of glutamate and aspartate which are
      linked to the TCA cycle via reversible aminotransferase reactions are likely to
      be responsible for the observed delay in equilibration of TCA cycle
      intermediates. Furthermore, it was estimated that 11% of the glucose taken up by
      astrocytes was diverted to the pentose phosphate pathway. In addition,
      considerable fluxes through pyruvate carboxylase [PC; PC/pyruvate dehydrogenase
      (PDH) ratio = 0.5], malic enzyme (5% of the total pyruvate production), and
      catabolism of branched-chained amino acids (contributing with ~40% to total
      acetyl-CoA produced) confirmed the significance of these pathways to astrocytic
      metabolism. Consistent with the need of maintaining cytosolic redox potential,
      the fluxes through the malate-aspartate shuttle and the PDH pathway were
      comparable. Finally, the estimated glutamate/alpha-ketoglutarate exchange rate
      (~0.7 MUmol mg prot-1 h-1) was similar to the TCA cycle flux. In conclusion, this
      work demonstrates the potential of isotopic transient MFA for a comprehensive
      analysis of energy metabolism.

PMID- 21941481
TI  - Focal dermal hypoplasia with uterus bicornis and renal ectopia: case report and
      review of the literature.
AB  - Focal dermal hypoplasia (FDH) is a rare inherited genodermatosis with an X-linked
      dominant trait. FDH is associated with skin defects and other abnormalities of
      bone, nails, hair, limbs, teeth and eyes. We present the case of a 26-year-old
      female in the 27th pregnancy week and a previous history of miscarriage. After
      careful physical examination and dermal biopsy, histopathology revealed that the
      patient was a carrier of FDH. This is the first report in the literature
      describing that FDH is associated with uterus bicornis and renal ectopia. Our
      association could be attributable to early embryonic abnormalities related with
      FDH because both the uterus bicornis and the renal ectopia originate around the
      3th-6th week of embryonic development. We are unable to confirm that the
      miscarriages were caused by inherited FDH or that uterus bicornis was the cause.
      We conducted a literature review using the following terms: FDH, Goltz syndrome,
      uterus bicornis, and renal ectopia.

PMID- 21941482
TI  - Malignant fibrous histiocytoma with in-transit metastasis.
AB  - Malignant fibrous histiocytoma (MFH) is the most common fibroblastic tumor, but
      its cutaneous metastasis, especially in-transit metastasis, is extremely rare. We
      describe the case of a 30-year-old Japanese man with a recurrent MFH on the scalp
      accompanied by in-transit metastasis, which had been treated as a benign skin
      tumor 8 years before. The main bulk of the recurrent tumor was located in the
      dermis, but the metastatic tumor was mainly located in the subcutis. Generally,
      atypical fibroxanthoma, also known as cutaneous MFH, is rarely metastasized and
      presents a benign clinical course. Since there is a great difference between the
      prognosis of MFH and atypical fibroxanthoma, precise diagnosis of the primary
      tumor is essential.

PMID- 21941483
TI  - Spontaneous remission of solitary-type infantile myofibromatosis.
AB  - Infantile myofibromatosis is a rare fibrous tumor of infancy. The cutaneous
      solitary type has typically an excellent prognosis. However, histologically, it
      is important to rule out leiomyosarcoma, which has a poor prognosis. The low
      frequency of mitosis was definitive for a diagnosis of infantile myofibromatosis.
      We present a cutaneous solitary-type case of infantile myofibromatosis. Following
      incisional biopsy, the tumor remitted spontaneously.

PMID- 21941484
TI  - Long-time survival of a patient with metastatic pancreatic cancer: a case report.
AB  - Pancreatic cancer is a malignant neoplasm of the pancreas. It does not cause any
      symptoms in the early stage, and later symptoms are nonspecific, thus the disease
      is usually diagnosed when already advanced. In 2008, pancreatic cancer ranked
      eighth on the list of the 10 most common cancers among men in Croatia and tenth
      on the list of the most common cancers among Croatian women. Pancreatic cancer
      has a poor prognosis, with a survival time of only 6-8 months for metastatic
      disease. Gemcitabine is the standard chemotherapeutic option. Other
      chemotherapeutic agents include5-fluorouracil and leucovorin. In this paper, we
      present a case of a patient diagnosed with locally advanced and metastatic
      pancreatic cancer, who is still alive and currently receives his fourth line of
      chemotherapy 5 years after the diagnosis. Following disease progression on
      gemcitabine chemotherapy, he was treated with chemoradiotherapy which, however,
      had no effect. We then applied cisplatin monochemotherapy which offered excellent
      disease control, was well tolerated by the patient and, although somewhat
      obsolete in this form, showed to be a valuable chemotherapeutic option.

PMID- 21941485
TI  - Severe encephalopathy, lactic acidosis, vegetative instability and neuropathy
      with 5-Fluorouracil treatment - pyrimidine degradation defect or beriberi?
AB  - We present the case of a 19-year-old female with nasopharyngeal carcinoma, who
      received two courses of chemotherapy with 5-fluorouracil (5-FU) in combination
      with folic acid and cisplatin. Upon developing esophageal strictures in the
      course of her radiotherapy, she required total parenteral nutrition. In the
      course of therapy, the patient developed severe multisystem failure with
      encephalopathy, lactic acidosis, vegetative instability and neuropathy. The
      treatment with 5-FU can lead to severe toxicity due to enzyme deficiencies in the
      degradation of pyrimidines, but it can also lead to thiamine deficiency with the
      classic symptoms of beriberi. Beriberi is a rare disorder, usually attributed to
      malnutrition or alcoholism. 5-FU has been shown to induce thiamine depletion.
      Reduced food intake or total parenteral nutrition devoid of vitamin supplements
      may aggravate symptoms. We were unable to find a genetic cause for increased 5-FU
      toxicity in our patient, ruling out deficiencies of dihydropyrimidine
      dehydrogenase, dihydropyrimidinase or beta-ureidopropionase and double-strand
      break repair deficits. We come to the conclusion that, even without any definable
      enzyme deficiency, treatment with 5-FU can lead to high toxicity due to thiamine
      deficiency if vitamin supplementation is not undertaken.

PMID- 21941486
TI  - A case of highly aggressive extraskeletal myxoid chondrosarcoma.
AB  - Extraskeletal myxoid chondrosarcoma (EMC) is a soft tissue malignancy
      characterized by specific chromosomal abnormalities involving the TEC gene. This
      disease has historically been considered largely indolent both histologically and
      clinically. Rarer subsets of EMC exist that demonstrate aggressive
      histopathologic features and clinical behavior, though it remains unclear whether
      or not aggressive histopathology is predictive of outcome. Herein we present a
      case of EMC with aggressive histopathologic features that underwent rapid
      clinical progression despite initial treatment with curative intent. This case
      provides the context for a discussion of the existing literature regarding
      treatment, prognosis, pathology, and genetic/molecular features of EMC in general
      and aggressive EMC specifically.

PMID- 21941487
TI  - Leukocytoclastic vasculitis after long-term treatment with sunitinib: a case
      report.
AB  - We report on a 63-year-old woman, previously in good health, who had undergone
      nephrectomy for clear cell renal cell carcinoma in 2002. Because of systemic
      relapse with multiple lung metastases in 2006, the patient was treated with
      sunitinib 50 mg daily on a 4-weeks on-/2-weeks off-schedule. After 3 years of
      treatment, she developed a purpuric rash on her feet and trunk. Biopsy revealed
      leukocytoclastic vasculitis. No other organ involvement was diagnosed. She was
      started on oral prednisone 30 mg daily with rapid resolution of the vasculitic
      skin lesions. Sunitinib was temporally discontinued and reintroduced at the same
      dose level. Reappearance of a less serious vasculitis after 2 cycles of re
      treatment was resolved in the weeks off-treatment and by reducing the dose of
      sunitinib along with 5 mg of prednisone daily. One year after the diagnosis, the
      patient is still on this therapy. Oncology providers should be aware of this rare
      but potentially serious, possible adverse effect of sunitinib.

PMID- 21941488
TI  - Macroglossia due to Systemic Amyloidosis: Is There a Role for Radiotherapy?
AB  - BACKGROUND: Macroglossia due to amyloid depositions can cause cosmetic problems
      and functional disability, and can lead to life-threatening airway obstruction.
      Management of macroglossia in systemic amyloidosis is controversial, and the role
      of surgery is unclear. CASE DESCRIPTION: We present a case of a 66-year-old woman
      affected by macroglossia due to light chain amyloidosis who presented with eating
      and breathing difficulties. Because of prior successful results of radiotherapy
      for localized amyloid disease, our patient was treated with external beam
      radiation therapy (20 Gy in 10 fractions). The treatment was well tolerated by
      the patient. However, her systemic amyloidosis progressed, with a subclinical
      increase in tongue width. CONCLUSIONS: This is the first reported use of
      radiotherapy for amyloidosis of the tongue. There was no evidence of benefit
      using a total dose of 20 Gy. This therapeutic modality is not recommended for the
      routine management of macroglossia.

PMID- 21941489
TI  - Neuroblastoma presenting with acute kidney injury, hyponatremic-hypertensive-like
      syndrome and nephrotic proteinuria in a 10-month-old child.
AB  - Neuroblastoma is the most common extracranial solid tumor in childhood. Its
      presenting signs and symptoms may be highly variable, depending on the location
      of the primary tumor and its local or metastatic diffusion and, rarely, with
      paraneoplastic syndrome such as opsoclonus-myoclonus-ataxia syndrome and
      gastrointestinal disturbances, due to autoantibodies or to aberrant secretion of
      vasoactive intestinal peptide. Herein we describe a 10-month-old child with
      neuroblastoma presenting with a complex clinical picture characterized by acute
      kidney injury manifested by renal insufficiency and signs and symptoms of
      tubulointerstitial damage, with polyuria, polydipsia, glucosuria, aminoaciduria
      and hypochloremic metabolic alkalosis, and of glomerular damage with heavy
      proteinuria. Imaging study documented a suprarenal mass enveloping the aorta and
      its abdominal and renal ramifications and bilaterally renal veins. This clinical
      picture shows some analogies with the hyponatremic-hypertensive syndrome
      concerning the renovascular disease; however, in absence of systemic arterial
      hypertension, the heavy proteinuria and the polyuria could be explained by
      sectional increased intraglomerular pressure, due to local renal blood vessels
      constriction. Hypochloremic metabolic alkalosis probably developed because of
      local production of renin, responsible of renin-angiotensin-aldosterone system
      activation, but above all because of chloride loss through sweating. The long
      lasting dehydration, due to vomiting, sweating and polyuria, caused prolonged
      prerenal failure evolving in proximal tubular damage manifestations.

PMID- 21941490
TI  - Carcinomatous meningitis: the natural history of successfully treated metastatic
      bladder cancer.
AB  - Carcinomatous meningitis due to bladder cancer is a rare entity reported only in
      case reports. Optimal therapy is thus poorly defined with earlier cases reporting
      an unsuccessful outcome. Here we report a case of late carcinomatous meningitis
      secondary to transitional cell carcinoma (TCC) of the bladder occurring in a
      patient in complete remission. He was successfully treated with intrathecal
      methotrexate and whole brain irradiation and experienced prolonged survival after
      treatment. With modern chemotherapy increasing complete remissions and survival
      rates in patients with TCC, more and more patients are being reported with
      carcinomatous meningitis. We raise the question of whether central nervous system
      prophylaxis should be considered in patients with TCC achieving a complete
      remission to chemotherapy in the metastatic setting.

PMID- 21941491
TI  - Long-Term Relapse-Free Survival by Interdisciplinary Collaboration in a Patient
      with Metastatic Pancreatic Cancer (UICC IV).
AB  - INTRODUCTION: The prognostic outlook for patients suffering from pancreatic
      cancer is generally poor. Particularly in cases of advanced and metastatic
      disease, long-term relapse-free survival may be achieved only in a few cases.
      CASE REPORT: A 45-year-old patient presented with metastatic pancreatic cancer.
      Liver metastases had been intra-operatively confirmed by histology. Prior to
      initiating treatment, a portacath was surgically implanted. Subsequently, the
      patient received a weekly dose of 1,000 mg/m(2) gemcitabine combined with 2,000
      mg/m(2) high-dose 5-fluorouracil as a 24-hour infusion for palliative treatment.
      As the patient was suffering from a stenosis of the ductus hepaticus communis, an
      endoprosthesis was primarily implanted. After 18 applications of chemotherapy
      during which only low toxic side effects such as nausea, vomiting and alopecia
      (NCI-CTC grade 1) presented, a partial remission of the primary tumor was
      observed. In the course of chemotherapy treatment, the carbohydrate antigen 19-9
      tumor marker value normalized. Thus, the interdisciplinary tumor board of the
      University of Erlangen decided to perform a laparoscopy to evaluate the status of
      liver metastases after palliative chemotherapy treatment. Subsequently, the
      primary tumor could be completely resected (pT2, pN0, pM0, L0, V0, G2, R0); liver
      metastases were not observed. Eight years after the initial diagnosis, the
      patient is relapse-free, professionally fully integrated and presents with an
      excellent performance status. CONCLUSION: Patients suffering from metastatic
      pancreatic cancer may benefit from treatment combinations with palliative intent.
      In singular cases, patients may even have a curative treatment option, provided a
      close interdisciplinary collaboration exists.

PMID- 21941492
TI  - First Experiences with Navigated Radio-Guided Surgery Using Freehand SPECT.
AB  - BACKGROUND: Sentinel lymph node biopsy (SLNB) in melanoma using one-dimensional
      gamma probes is a standard of care worldwide. Reports on the performance are
      claimed by most groups to successfully detect the SLNs during the surgical
      procedure in almost 100% of the patients. In clinical practice, however, several
      issues remain which are usually not addressed: the difficulty of intraoperative
      detection of deeply located nodes, SLN detection in obese patients or in the
      groin and the impossibility to make a scan of the entire wound after SLN
      resection to avoid false negative testing for eventually remaining SLNs.
      MATERIALS AND METHODS: The concept behind freehand SPECT is to combine a gamma
      probe as used for conventional radio-guided surgery with a tracking system as
      used in neurosurgical navigation. From this combination and a proper algorithm
      framework the 3D reconstruction of radioactivity distributions and displaying
      these intraoperatively is possible. CONCLUSION: In summary, the feasibility of
      freehand SPECT could be shown and provides an image-guided SLNB and a truly
      minimally invasive and optimized surgical procedure.

PMID- 21941493
TI  - Invasive recurrence of an intestinal-type mucinous epithelial neoplasm of low
      malignant potential: case report and review of the literature.
AB  - Pseudomyxoma peritonei is only rarely seen in conjunction with primary ovarian
      tumors. It has been suggested that only ruptured mucinous tumors arising in
      ovarian mature cystic teratomas can result in this clinical picture. We describe
      a case of a late invasive recurrence of a mucinous intestinal-type borderline
      ovarian tumor arising from a mature teratoma after complete surgical debulking.
      Borderline ovarian tumors behave indolently in the overwhelming majority of
      cases, and the prognosis is therefore usually outstanding.

PMID- 21941495
TI  - Acute cerebral infarction masked by a brain tumor.
AB  - We report on an 81-year-old man who presented with left limbs weakness and was
      brought to the emergency room where a brain computed tomography revealed a tumor
      at the right parasellar region. The patient was admitted to the neurosurgery
      department, and the symptoms were thought to be due to the tumor mass effect. The
      final diagnosis turned out to be acute ischemic infarction with an incidentally
      found brain tumor following angiography and magnetic resonance imaging.

PMID- 21941494
TI  - Herpes simplex encephalitis with two false-negative cerebrospinal fluid PCR tests
      and review of negative PCR results in the clinical setting.
AB  - INTRODUCTION: Herpes simplex virus encephalitis (HSE) is an acute infection
      accompanied by significant morbidity and mortality with the diagnosis often made
      by cerebrospinal fluid (CSF) polymerase chain reaction (PCR) testing. CASE
      PRESENTATION: We report a case of a healthy 35-year-old woman presenting with
      altered mental status. Due to suspicion of herpes encephalitis, a CSF PCR for
      herpes virus was sent for examination and acyclovir was started. The patient had
      an immediate response to acyclovir; however, when the PCR returned negative she
      was discharged without therapy. The altered mental status returned and she was
      started on acyclovir therapy and a second CSF PCR sample was sent and was again
      negative. MRI performed at initial hospitalization was negative, but a repeat MRI
      demonstrated bilateral temporal lobe involvement suggestive of herpes
      encephalitis. The patient was successfully treated for 21 days with acyclovir.
      CONCLUSION: CSF PCR for herpes virus is highly sensitive and specific and remains
      the standard for diagnosing herpes encephalitis. Clinicians should be aware of
      the pitfalls of CSF PCR testing, specifically false-negative results. Although
      rare, these false negatives can result in premature termination of treatment.

PMID- 21941496
TI  - Rapidly progressive corticobasal degeneration syndrome.
AB  - INTRODUCTION: Corticobasal syndrome (CBS) has a heterogeneous clinical
      presentation with no specific pathologic substratum. Its accurate diagnosis is a
      challenge for neurologists; in order to establish CBS definitively, postmortem
      confirmation is required. Some clinical and radiological features can help to
      distinguish it from other neurodegenerative conditions, such as Creutzfeldt-Jakob
      disease (CJD). CLINICAL CASE: A 74-year-old woman presented with language
      impairment, difficulty in walking and poor attentiveness that had begun 10 days
      before. Other symptoms, such as asymmetrical extra-pyramidal dysfunction, limb
      dystonia and 'alien limb' phenomena, were established over the next 2 months,
      with rapid progression. Death occurred 3 months after symptom onset. Laboratory
      results were normal. Initially, imaging only showed restricted diffusion with
      bilateral parieto-occipital gyri involvement on DWI-MRI, with unspecific EEG
      changes. An autopsy was performed. Brain neuropathology confirmed sporadic CJD
      (sCJD). CONCLUSIONS: CBS is a heterogeneous clinical syndrome whose differential
      diagnosis is extensive. CJD can occasionally present with clinical
      characteristics resembling CBS. MRI detection of abnormalities in some sequences
      (FLAIR, DWI), as previously reported, has high diagnostic utility for sCJD
      diagnosis - especially in early stages - when other tests can still appear
      normal. Abnormalities on DWI sequencing may not correlate with neuropathological
      findings, suggesting a functional basis to explain the changes found.

PMID- 21941497
TI  - Atypical postpartum stroke presenting as opalski syndrome: case report and review
      of the literature.
AB  - BACKGROUND AND PURPOSE: We present the first case of combined arterial (vertebral
      artery dissection) and venous [central sinus vein thrombosis (CSVT)] diseases
      presenting as Opalski syndrome in a female patient following induced delivery.
      CASE DESCRIPTION: A 32-year-old woman was admitted to our institute two weeks
      after induced delivery with intriguing neurological findings that were finally
      diagnosed as a combined venous-arterial disease. Although she was referred
      diagnosed with CSVT, her neurological findings indicated Wallenberg 'plus'
      syndrome with ipsilateral hemiparesis (Opalski syndrome), further confirmed by
      neuroimaging revealing arterial disease (vertebral artery dissection) combined
      with incidental acute CSVT. Coagulation, gynecological and cardiac problems were
      ruled out. Treatment consisted of continuous heparin with rigorous control of her
      blood pressure. Nine days later, the patient was discharged with prominent
      improvements. Most of the symptoms resolved following 3 months of rehabilitation.
      CONCLUSIONS: Atypical strokes (such as Opalski syndrome) might present in
      postpartum patients. This rare diagnosis should be suspected in patients with
      Wallenberg 'plus' syndrome, and neuroimaging studies for determining the presence
      of arterial disease and brain stem lesions should be performed. Concomitant CSVT
      is rare and might mislead. Fine diagnosis followed by immediate conservative
      treatment can be of great benefit.

PMID- 21941499
TI  - Ulnar neuropathy as a complication of retinal detachment surgery and face-down
      positioning.
AB  - PURPOSE: To report a case of bilateral ulnar neuropathy as an extraocular
      complication following retinal detachment surgery and face-down positioning.
      METHODS: Case report. RESULTS: Bilateral hypoesthesia and numbness of the 4th and
      5th finger started 2 weeks after vitrectomy for retinal detachment and face-down
      positioning. Due to progressive symptoms 6 months later, unilateral ulnar nerve
      decompression at the elbow was performed. CONCLUSIONS: This case report
      demonstrates that strict face-down positioning bears the risk of ulnar
      neuropathy.

PMID- 21941498
TI  - Cytomegalovirus retinitis in an immunocompromised infant: a case report and
      review of the literature.
AB  - PURPOSE: To describe a case of bilateral cytomegalovirus retinitis (CMVR) in an
      immunocompromised infant. METHODS: A 4-month-old male infant with severe combined
      immunodeficiency syndrome was examined for the presence of CMVR. Ocular
      involvement was recorded and monitored by digital imaging. RESULTS: The child had
      bilateral CMVR, with a fine granular pattern, present both in the peripheral
      retina and posterior pole. There was no vitritis. The active areas of retinitis
      progressively resolved with intravenous ganciclovir treatment. At the 3-month
      follow-up examination, no recurrence was observed. CONCLUSION: Ganciclovir
      treatment was effective in this case. The prognosis depends on rapid institution
      of effective antiviral therapy and on a patient's systemic immunocompetence.

PMID- 21941500
TI  - Fast Resolution of Recurrent Pronounced Macular Edema following Intravitreal
      Injection of Dexamethasone 0.7 mg.
AB  - PURPOSE: To report the fast resolution of recurrent pronounced macular edema due
      to central retinal vein occlusion (CRVO) within 72 h following intravitreal
      injection of dexamethasone 0.7 mg (Ozurdex(r)). METHODS: An interventional case
      report with optical coherence tomography scans and fluorescein angiographic
      pictures. RESULTS: A 69-year-old Caucasian man underwent intravitreal injection
      of dexamethasone 0.7 mg due to incomplete CRVO. He had previously undergone 6
      intravitreal injections of bevacizumab 1.25 mg (Avastin(r)) and a C-grid laser
      photocoagulation over an interval of 16 months. After repeated recurrences of
      macular edema, the injection of dexamethasone reduced the macular edema from 570
      MUm preoperatively to 246 MUm postoperatively within 72 h following the
      injection. Best-corrected visual acuity improved from 0.1 to 0.6 within the same
      interval. CONCLUSION: Dexamethasone can lead to a very fast reduction of macular
      edema in patients with vision loss due to CRVO and may facilitate an immediate
      visual rehabilitation. Retinal anatomy and visual acuity may be restored even in
      long-standing, recurrent cases.

PMID- 21941501
TI  - Massive bilateral choroidal detachment induced by administration of topiramate.
AB  - Topiramate is a sulfa-derivative antiepileptic drug which is also used for other
      indications such as essential tremor. A 79-year-old male was admitted to our
      center due to acute bilateral painless decline of vision. One month before
      admission, he had experienced essential tremor and treatment with topiramate 50
      mg/day and propranolol 40 mg/day. Best-corrected visual acuity was 20/800 OD and
      20/600 OS. Both eyes had normal anterior chamber depths and irides. Intraocular
      pressure was 10 mm Hg in the right eye and 11 mm Hg in the left eye. Retinal
      examination showed notable choroidal detachments in all quadrants of the
      periphery, which were confirmed by ultrasonography. Refraction showed no myopic
      shift. The administration of topiramate was discontinued as a potential causative
      agent for this condition. During follow-up, choroidal detachment and visual
      acuity gradually resolved. In this study, we described the first case of isolated
      massive choroidal detachment induced by topiramate.

PMID- 21941502
TI  - A Case of Retinitis Pigmentosa Requiring Vitrectomy because of Repeated Vitreous
      Hemorrhage.
AB  - A male patient with retinitis pigmentosa (RP) accompanied by repeated vitreous
      hemorrhage in both eyes underwent unilateral vitrectomy. Visual acuity recovered
      to 0.8 in the operated right eye, and no hemorrhage, complications or progression
      of RP were observed. Fluorescein angiography performed 2 months after surgery
      detected neovascularization at the optic disc in the operated right eye, but not
      in the non-operated left eye, and no avascular areas were found in either eye.
      Vitrectomy may be effective for the treatment of RP accompanied by vitreous
      hemorrhage.

PMID- 21941503
TI  - Bilateral simultaneous anterior ischemic optic neuropathy associated with
      sildenafil.
AB  - We report a case of simultaneous bilateral nonarteritic anterior ischemic optic
      neuropathy (NAION) due to sildenafil use. A 55-year-old man with an unremarkable
      medical history presented simultaneous bilateral NAION 8 months after continuous
      use of sildenafil 4-5 times a month. At presentation, visual acuity (VA) was 0.7
      in the right eye (RE) and 0.9 in the left eye (LE). The visual field showed an
      inferior altitudinal defect in both eyes and a fundus examination revealed
      prominent optic disc edema in the RE and a crowded optic disc in the LE. The
      patient was counseled to discontinue sildenafil, and 3 weeks later VA was 1.0 in
      both eyes and the optic disc edema in the RE was resolved. However, a visual
      field defect remained in the RE. Three months later, visual fields were
      unchanged. To the best of our knowledge, this is the first reported case of
      simultaneous bilateral NAION due to sildenafil use.

PMID- 21941504
TI  - Reemergence of syphilitic uveitis masquerading as other diseases: a report of two
      cases.
AB  - During a 6-month period in 2010, 2 patients with uveitis were examined at our
      department and diagnosed with ocular syphilis. They initially presented with
      symptoms and signs resembling Harada's disease and Behcet's disease and were
      therefore treated with systemic steroids with suboptimal responses. When
      laboratory workup revealed neurosyphilis, they were given a course of intravenous
      penicillin G, which led to significant clinical and visual improvement.
      Epidemiological data indicates a worldwide reemergence of syphilis and a high
      degree of suspicion is necessary in view of its multitude of presenting ocular
      signs without pathognomonic features.

PMID- 21941505
TI  - Artiflex toric phakic intraocular lens implantation in congenital nystagmus.
AB  - CASE: A 44-year-old woman with congenital nystagmus and myopic astigmatism in
      both eyes who was submitted to phakic intraocular lens (pIOL) implantation.
      METHODS: Full ophthalmologic examination including refractive status, corrected
      (CDVA) and uncorrected (UCVA) monocular and binocular visual acuities, ocular
      motility, slit-lamp evaluation, tonometry and fundoscopy before and after
      implantation of toric pIOLs (Artiflex; Ophtec BV, The Netherlands) in both eyes.
      RESULTS: Preoperative logMAR CDVA were 0.699 and 0.420 in the right and left eye,
      respectively. Three months after surgery, logMAR UCVA were 0.398 and 0.182,
      reaching binocular logMAR UCVA of 0.132. There were no changes in nystagmus
      characteristics after surgery. CONCLUSIONS: pIOL implantation may be a safe and
      suitable treatment to correct high refractive errors in patients with congenital
      nystagmus. Significant improvement in CDVA and UCVA can be achieved.

PMID- 21941506
TI  - Post-cataract surgery visual disturbance in a retinitis pigmentosa patient with
      asteroid hyalosis.
AB  - A patient with retinitis pigmentosa showed visual disturbances following
      successful cataract surgery. He had a dense asteroid hyalosis in the eye before
      cataract surgery. After the surgery he noticed that his vision became worse. The
      visual disturbance was explained as being caused by the progression of retinal
      degeneration. Although the electroretinogram was non-recordable, the degeneration
      of macular area appeared relatively small. We considered that dense asteroid
      hyalosis was responsible for his visual disturbances, and pars plana vitrectomy
      (PPV) was performed to remove the asteroid hyalosis. After the PPV, rapid
      improvement of his visual acuity was observed. Cataract surgery may affect the
      status of asteroid hyalosis and cause rapid visual loss. PPV should be considered
      for retinitis pigmentosa patients with dense asteroid hyalosis, especially when a
      large decrease in visual acuity is noted shortly after cataract surgery.

PMID- 21941507
TI  - Posttraumatic giant macular hole.
AB  - INTRODUCTION: Large macular holes secondary to blunt trauma are sometimes seen in
      young patients within the spectrum of alterations produced by ocular trauma.
      METHODS: Observational case report. A 32-year-old woman who had received a blunt
      trauma (a blow from a fist) to her right eye 10 years previously had experienced
      a decrease in visual acuity ever since. RESULTS: Clinical photographs,
      fluorescein angiography and optic coherent tomography images revealed a very
      large macular hole of approximately 1,920 MUm in diameter. CONCLUSION: This case
      is an uncommonly large variant of a macular hole secondary to blunt trauma in a
      young patient.

PMID- 21941508
TI  - Pseudoexfoliation and opacification of intraocular lenses.
AB  - PURPOSE: To report two cases of spoke-like intraocular lens (IOL) opacification
      that resembles pseudoexfoliation of the crystalline lens. METHODS: Case series
      presentation. RESULTS: Patient 1 developed a circle of spoke-like opacification
      on the anterior IOL surface 7 years after phacoemulsification. Patient 2 had
      paracentral anterior surface IOL opacification 18 months after cataract
      extraction and clinical pseudoexfoliation in the fellow eye. CONCLUSION: Spoke
      like anterior IOL opacification should raise the suspicion of pseudoexfoliation
      syndrome.

PMID- 21941509
TI  - Ultraviolet-a light and riboflavin therapy for acanthamoeba keratitis: a case
      report.
AB  - PURPOSE: To report ultraviolet-A (UV-A) light treatment in a patient with
      Acanthamoeba keratitis (AK). METHODS: Interventional case report. A standard
      protocol for ultraviolet corneal therapy, with a power emission of 3 mW/cm(2) and
      a wavelength of 370 nm, was used. The protocol included an 8-nm bandwidth at a 54
      mm distance measured with a collimation system of diodes as well as a protective
      shield of riboflavin in a case of documented AK. RESULTS: A 54-year-old female
      patient with AK, showing no therapeutic response to a wide variety of topical
      antimicrobial agents and with a visual acuity of 20/400, was treated with UV-A
      therapy. The patient displayed a favourable response in the first 24 h after
      treatment, with improvement of symptoms, visual acuity (to 20/200) and
      biomicroscopy cornea with haze degree I. By the third week post-treatment, the
      patient was symptom-free. Her visual acuity was 20/30, and the affected cornea
      was clear. Five months after treatment, there had been no recurrence, and her
      vision was 20/20. CONCLUSIONS: Treatment with UV-A light was an effective therapy
      in this case of AK.

PMID- 21941510
TI  - Vitamin d and susceptibility of chronic lung diseases: role of epigenetics.
AB  - Vitamin D deficiency is linked to accelerated decline in lung function, increased
      inflammation, and reduced immunity in chronic lung diseases. Epidemiological
      studies have suggested that vitamin D insufficiency is associated with low lung
      function in susceptible subjects who are exposed to higher levels of
      environmental agents (airborne particulates). Recent studies have highlighted the
      role of vitamin D and vitamin D receptor (VDR) in regulation of several genes
      that are involved in inflammation, immunity, cellular proliferation,
      differentiation, and apoptosis. Vitamin D has also been implicated in reversal of
      steroid resistance and airway remodeling, which are the hallmarks of chronic
      obstructive pulmonary disease (COPD) and severe asthma. VDR protein level is
      decreased in lungs of patients with COPD. VDR deficient mice develop an abnormal
      lung phenotype with characteristics of COPD, such as airspace enlargement and
      decline in lung function associated with increased lung inflammatory cellular
      influx, and immune-lymphoid aggregates formation. Dietary vitamin D may regulate
      epigenetic events, in particular on genes which are responsible for COPD
      susceptibility. Active metabolite of vitamin D, 1,25-dihydroxyvitamin D(3) plays
      an essential role in cellular metabolism and differentiation via its nuclear
      receptor (VDR) that cooperates with several other chromatin modification enzymes
      (histone acetyltransferases and histone deacetylases), thereby mediating complex
      epigenetic events in vitamin D signaling and metabolism. This review provides an
      update on the current knowledge and understanding on vitamin D, and
      susceptibility of chronic lung diseases in relation to the possible role of
      epigenetics in its molecular action. Understanding the molecular epigenetic
      mechanism of vitamin D/VDR would provide rationale for dietary vitamin D-mediated
      intervention in prevention and management of chronic lung diseases linked with
      vitamin D deficiency.

PMID- 21941511
TI  - Hydrogen Sulfide in the RVLM and PVN has No Effect on Cardiovascular Regulation.
AB  - Hydrogen sulfide (H(2)S) is now recognized as an important signaling molecule and
      has been shown to have vasodilator and cardio-protectant effects. More recently
      it has been suggested that H(2)S may also act within the brain to reduce blood
      pressure (BP). In the present study we have demonstrated the presence of the
      H(2)S-producing enzyme, cystathionine-beta-synthase (CBS) in the rostral
      ventrolateral medulla (RVLM), and the hypothalamic paraventricular nucleus (PVN),
      brain regions with key cardiovascular regulatory functions. The cardiovascular
      role of H(2)S was investigated by determining the BP, heart rate (HR), and lumbar
      sympathetic nerve activity (LSNA) responses elicited by a H(2)S donor sodium
      hydrogen sulfide (NaHS) or inhibitors of CBS, microinjected into the RVLM and
      PVN. In anesthetized Wistar Kyoto rats bilateral microinjections of NaHS (0.2
      2000 pmol/side) into the RVLM did not significantly affect BP, HR, or LSNA,
      compared to vehicle. Similarly, when the CBS inhibitors, amino-oxyacetate (AOA;
      0.1-1.0 nmol/side) or hydroxylamine (HA; 0.2-2.0 nmol/side), were administered
      into the RVLM, there were no significant effects on the cardiovascular variables
      compared to vehicle. Microinjections into the PVN of NaHS, HA, and AOA had no
      consistent significant effects on BP, HR, or LSNA compared to vehicle. We also
      investigated the cardiovascular responses to NaHS microinjected into the RVLM and
      PVN in spontaneously hypertensive rats. Again, there were no significant effects
      on BP, HR, and LSNA. Together, these results suggest that H(2)S in the RVLM and
      PVN does not have a major role in cardiovascular regulation.

PMID- 21941512
TI  - Functional characterization of water transport and cellular localization of three
      aquaporin paralogs in the salmonid intestine.
AB  - Intestinal water absorption is greatly enhanced in salmonids upon acclimation
      from freshwater (FW) to seawater (SW); however, the molecular mechanism for water
      transport is unknown. We conducted a pharmacological characterization of water
      absorption in the rainbow trout intestine along with an investigation of the
      distribution and cellular localization of three aquaporins (Aqp1aa, -1ab, and 
      8ab) in pyloric caeca, middle (M), and posterior (P) intestine of the Atlantic
      salmon. In vitro iso-osmotic water absorption (J(v)) was higher in SW than FW
      trout and was inhibited by (mmol L(-1)): 0.1 KCN (41%), 0.1 ouabain (72%), and
      0.1 bumetanide (82%) suggesting that active transport, Na(+), K(+)-ATPase and
      Na(+), K(+), 2Cl(-)-co-transport are involved in establishing the driving
      gradient for water transport. J(v) was also inhibited by 1 mmol L(-1) HgCl(2),
      serosally (23% in M and 44% in P), mucosally (27% in M), or both (61% in M and
      58% in P), suggesting involvement of both apical and basolateral aquaporins in
      water transport. The inhibition was antagonized by 5 mmol L(-1) mercaptoethanol.
      By comparison, 10 mmol L(-1) mucosal tetraethylammonium, an inhibitor of certain
      aquaporins, inhibited J(v) by 20%. In the presence of glucose, mucosal addition
      of phloridzin inhibited water transport by 20%, suggesting that water transport
      is partially linked to the Na(+)-glucose co-transporter. Using polyclonal
      antibodies against salmon Aqp1aa, -1ab, and -8ab, we detected Aqp1aa, and -1ab
      immunoreactivity in the brush border and sub-apical region of enterocytes in all
      intestinal segments. The Aqp8ab antibody showed a particularly strong
      immunoreaction in the brush border and sub-apical region of enterocytes
      throughout the intestine and also stained lateral membranes and peri-nuclear
      regions though at lower intensity. The present localization of three aquaporins
      in both apical and lateral membranes of salmonid enterocytes facilitates a model
      for transcellular water transport in the intestine of SW-acclimated salmonids.

PMID- 21941513
TI  - Glycosylation of Twisted Gastrulation is Required for BMP Binding and Activity
      during Craniofacial Development.
AB  - Twisted gastrulation (TWSG1) is a conserved, secreted glycoprotein that modulates
      signaling of bone morphogenetic proteins (BMPs) in the extracellular space.
      Deletion of exon 4 of mouse Twsg1 (mTwsg1) is associated with significant
      craniofacial defects. However, little is understood about the biochemical
      properties of the corresponding region of the protein. We have uncovered a
      significant role for exon 4 sequences as encoding the only two glycosylation
      sites of the mTWSG1 protein. Deletion of the entire exon 4 or mutation of both
      glycosylation sites within exon 4 abolishes glycosylation of mTWSG1. Importantly,
      we find that constructs with mutated glycosylation sites have significantly
      reduced BMP binding activity. We further show that glycosylation and activity of
      TWSG1 recombinant proteins vary markedly by cellular source. Non-glycosylated
      mTWSG1 made in E. coli has both reduced affinity for BMPs, as shown by surface
      plasmon resonance analysis, and reduced BMP inhibitory activity in a mandibular
      explant culture system compared to glycosylated proteins made in insect cells or
      murine myeloma cells. This study highlights an essential role for glycosylation
      in Twisted gastrulation action.

PMID- 21941514
TI  - Summation of large numerousness by newborn chicks.
AB  - Newly hatched domestic chicks, reared with identical objects, when presented with
      sets of 3 vs. 2 objects disappearing one-by-one behind separate screens,
      spontaneously inspected the screen occluding the larger set; even when the
      continuous variables (area or perimeter) were controlled for (Rugani et al.,
      2009). Here, using a similar paradigm, we investigated the ability of chicks to
      perform addition on larger sets of objects. Chicks imprinted on five identical
      objects, were presented at test with 6 vs. 9 objects which disappeared one-by-one
      (Exp. 1). In Exp. 2, the same overall number of objects (15) was used, but
      employing an increased ratio, i.e., 5 vs. 10. In both experiments, when
      continuous variables were not made equal, chicks spontaneously inspected the
      screen occluding the larger set. However, when the size of the objects was
      adjusted so as to make the total surface area or perimeter equal for the two
      sets, chicks did not exhibit any preference. Lack of choice in the control
      conditions could be due to a combination of preferences; to rejoin the larger
      numerousness as well as the bigger objects (Rugani et al., 2010a). In Exp. 3,
      chicks were familiarized, during imprinting, with objects of various dimensions,
      in an attempt to reduce or suppress their tendency to approach objects larger
      than the familiar ones. Again chicks failed to choose at test between 5 vs. 10
      objects when continuous variables were made equal. Results showed that chicks,
      after a one-by-one presentation of a large number of objects, rejoined the larger
      set. In order to choose the larger set, chicks estimated the objects in the two
      sets and then compared the outcomes. However, differently to what has been
      described for small numerousness, chicks succeeded only if non-numerical cues as
      well as numerical cues were available. This study suggests that continuous
      variables are computed by chicks for sets of objects that are not present at the
      same time and that are no longer visible at the time of choice.

PMID- 21941515
TI  - Depth perception and defensive system activation in a 3-d environment.
AB  - To survive, animals must be able to react appropriately (in temporal and
      behavioral terms) when facing a threat. One of the essential parameters
      considered by the defensive system is the distance of the threat, the "defensive
      distance." In this study, we investigate the visual depth cues that could be
      considered as an alarm cue for the activation of the defensive system. For this
      purpose, we performed an active-escape pain task in a virtual three-dimensional
      environment. In two experiments, we manipulated the nature and consistency of
      different depth cues: vergence, linear perspective, and angular size. By
      measuring skin conductance responses, we characterized the situations that
      activated the defensive system. We show that the angular size of the predator was
      sufficient information to trigger responses from the defensive system, but we
      also demonstrate that vergence, which can delay the emotional response in
      inconsistent situations, is also a highly reliable cue for the activation of the
      defensive system.

PMID- 21941516
TI  - Crossmodal constraints on human perceptual awareness: auditory semantic
      modulation of binocular rivalry.
AB  - We report a series of experiments utilizing the binocular rivalry paradigm
      designed to investigate whether auditory semantic context modulates visual
      awareness. Binocular rivalry refers to the phenomenon whereby when two different
      figures are presented to each eye, observers perceive each figure as being
      dominant in alternation over time. The results demonstrate that participants
      report a particular percept as being dominant for less of the time when listening
      to an auditory soundtrack that happens to be semantically congruent with the
      other alternative (i.e., the competing) percept, as compared to when listening to
      an auditory soundtrack that was irrelevant to both visual figures (Experiment
      1A). When a visually presented word was provided as a semantic cue, no such
      semantic modulatory effect was observed (Experiment 1B). We also demonstrate that
      the crossmodal semantic modulation of binocular rivalry was robustly observed
      irrespective of participants' attentional control over the dichoptic figures and
      the relative luminance contrast between the figures (Experiments 2A and 2B). The
      pattern of crossmodal semantic effects reported here cannot simply be attributed
      to the meaning of the soundtrack guiding participants' attention or biasing their
      behavioral responses. Hence, these results support the claim that crossmodal
      perceptual information can serve as a constraint on human visual awareness in
      terms of their semantic congruency.

PMID- 21941518
TI  - The grand challenge for psychoanalysis - and neuropsychoanalysis: taking on the
      game.

PMID- 21941517
TI  - Modulation of cross-frequency coupling by novel and repeated stimuli in the
      primate ventrolateral prefrontal cortex.
AB  - Adaptive behavior depends on an animal's ability to ignore uninformative stimuli,
      such as repeated presentations of the same stimulus, and, instead, detect
      informative, novel stimuli in its environment. The primate prefrontal cortex
      (PFC) is known to play a central role in this ability. However, the neural
      mechanisms underlying the ability to differentiate between repeated and novel
      stimuli are not clear. We hypothesized that the coupling between different
      frequency bands of the local field potential (LFP) underlies the PFC's role in
      differentiating between repeated and novel stimuli. Specifically, we hypothesized
      that whereas the presentation of a novel-stimulus induces strong cross-frequency
      coupling, repeated presentations of the same stimulus attenuates this coupling.
      To test this hypothesis, we recorded LFPs from the ventrolateral PFC (vPFC) of
      rhesus monkeys while they listened to a novel vocalization and repeated
      presentations of the same vocalization. We found that the cross-frequency
      coupling between the gamma-band amplitude and theta-band phase of the LFP was
      modulated by repeated presentations of a stimulus. During the first (novel)
      presentation of a stimulus, gamma-band activity was modulated by the theta-band
      phase. However, with repeated presentations of the same stimulus, this cross
      frequency coupling was attenuated. These results suggest that cross-frequency
      coupling may play a role in the neural computations that underlie the
      differentiation between novel and repeated stimuli in the vPFC.

PMID- 21941519
TI  - Vestibular function and quality of life in vestibular schwannoma: does size
      matter?
AB  - OBJECTIVES: Patients with vestibular schwannoma (VS) frequently suffer from
      disabling vestibular symptoms. This prospective follow-up study evaluates
      vestibular and auditory function and impairment of quality of life due to
      vertigo, dizziness, and imbalance in patients with unilateral VS of different
      sizes before/after microsurgical or radiosurgical treatment. METHODS: Thirty
      eight patients with unilateral VS were included. Twenty-two received
      microsurgery, 16 CyberKnife radiosurgery. Two follow-ups took place after a
      median of 50 and 186.5 days. Patients received a standardized neuro
      ophthalmological examination, electronystagmography with bithermal caloric
      testing, and pure-tone audiometry. Quality of life was evaluated with the
      Dizziness Handicap Inventory (DHI). Patient data was grouped and analyzed
      according to the size of the VS (group 1: <20 mm vs group 2: >=20 mm). RESULTS:
      In group 1, the median loss of vestibular function was +10.5% as calculated by
      Jongkees Formula (range -43 to +52; group 2: median +36%, range -56 to +90). The
      median change of DHI scores was -9 in group 1 (range -68 to 30) and +2 in group 2
      (-54;+20). Median loss of hearing was 4 dB (-42; 93) in group 1 and 12 dB in
      group 2 (5; 42). CONCLUSION: Loss of vestibular function in VS clearly correlates
      with tumor size. However, loss of vestibular function was not strictly associated
      with a long-term deterioration of quality of life. This may be due to central
      compensation of vestibular deficits in long-standing large tumors. Loss of
      hearing before treatment was significantly influenced by the age of the patient
      but not by tumor size. At follow-up 1 and 2, hearing was significantly influenced
      by the size of the VS and the manner of treatment.

PMID- 21941520
TI  - Gelsemium sempervirens and Animal Behavioral Models.

PMID- 21941521
TI  - Peripheral B cells as reservoirs for persistent HCV infection.

PMID- 21941522
TI  - Synthetic RNA silencing in bacteria - antimicrobial discovery and resistance
      breaking.
AB  - The increasing incidence and prevalence of antibiotic resistance in bacteria
      threatens the "antibiotic miracle." Conventional antimicrobial drug development
      has failed to replace the armamentarium needed to combat this problem, and novel
      solutions are urgently required. Here we review both natural and synthetic RNA
      silencing and its potential to provide new antibacterials through improved target
      selection, evaluation, and screening. Furthermore, we focus on synthetic RNA
      silencers as a novel class of antibacterials and review their unique properties.

PMID- 21941523
TI  - Efficient Probabilistic and Geometric Anatomical Mapping Using Particle Mesh
      Approximation on GPUs.
AB  - Deformable image registration in the presence of considerable contrast
      differences and large size and shape changes presents significant research
      challenges. First, it requires a robust registration framework that does not
      depend on intensity measurements and can handle large nonlinear shape variations.
      Second, it involves the expensive computation of nonlinear deformations with high
      degrees of freedom. Often it takes a significant amount of computation time and
      thus becomes infeasible for practical purposes. In this paper, we present a
      solution based on two key ideas: a new registration method that generates a
      mapping between anatomies represented as a multicompartment model of class
      posterior images and geometries and an implementation of the algorithm using
      particle mesh approximation on Graphical Processing Units (GPUs) to fulfill the
      computational requirements. We show results on the registrations of neonatal to 2
      year old infant MRIs. Quantitative validation demonstrates that our proposed
      method generates registrations that better maintain the consistency of anatomical
      structures over time and provides transformations that better preserve structures
      undergoing large deformations than transformations obtained by standard intensity
      only registration. We also achieve the speedup of three orders of magnitudes
      compared to a CPU reference implementation, making it possible to use the
      technique in time-critical applications.

PMID- 21941524
TI  - Sparse Representation of Deformable 3D Organs with Spherical Harmonics and
      Structured Dictionary.
AB  - This paper proposed a novel algorithm to sparsely represent a deformable surface
      (SRDS) with low dimensionality based on spherical harmonic decomposition (SHD)
      and orthogonal subspace pursuit (OSP). The key idea in SRDS method is to identify
      the subspaces from a training data set in the transformed spherical harmonic
      domain and then cluster each deformation into the best-fit subspace for fast and
      accurate representation. This algorithm is also generalized into applications of
      organs with both interior and exterior surfaces. To test the feasibility, we
      first use the computer models to demonstrate that the proposed approach matches
      the accuracy of complex mathematical modeling techniques and then both ex vivo
      and in vivo experiments are conducted using 3D magnetic resonance imaging (MRI)
      scans for verification in practical settings. All results demonstrated that the
      proposed algorithm features sparse representation of deformable surfaces with low
      dimensionality and high accuracy. Specifically, the precision evaluated as
      maximum error distance between the reconstructed surface and the MRI ground truth
      is better than 3 mm in real MRI experiments.

PMID- 21941525
TI  - CUDA-Accelerated Geodesic Ray-Tracing for Fiber Tracking.
AB  - Diffusion Tensor Imaging (DTI) allows to noninvasively measure the diffusion of
      water in fibrous tissue. By reconstructing the fibers from DTI data using a fiber
      tracking algorithm, we can deduce the structure of the tissue. In this paper, we
      outline an approach to accelerating such a fiber-tracking algorithm using a
      Graphics Processing Unit (GPU). This algorithm, which is based on the calculation
      of geodesics, has shown promising results for both synthetic and real data, but
      is limited in its applicability by its high computational requirements. We
      present a solution which uses the parallelism offered by modern GPUs, in
      combination with the CUDA platform by NVIDIA, to significantly reduce the
      execution time of the fiber-tracking algorithm. Compared to a multithreaded CPU
      implementation of the same algorithm, our GPU mapping achieves a speedup factor
      of up to 40 times.

PMID- 21941526
TI  - A Retrospective on Nuclear Receptor Regulation of Inflammation: Lessons from GR
      and PPARs.
AB  - Members of the nuclear receptor superfamily have vital roles in regulating
      immunity and inflammation. The founding member, glucocorticoid receptor (GR), is
      the prototype to demonstrate immunomodulation via transrepression of the AP-1 and
      NF-kappaB signaling pathways. Peroxisome proliferator-activated receptors (PPARs)
      have emerged as key regulators of inflammation. This review examines the history
      and current advances in nuclear receptor regulation of inflammation by the
      crosstalk with AP-1 and NF-kappaB signaling, focusing on the roles of GR and
      PPARs. A better understanding of the molecular mechanism by which nuclear
      receptors inhibit proinflammatory signaling pathways will enable novel therapies
      to treat chronic inflammation.

PMID- 21941527
TI  - Increased serum levels of uric acid are associated with sudomotor dysfunction in
      subjects with type 2 diabetes mellitus.
AB  - The aim of this paper was to assess serum uric acid (SUA) levels in patients with
      type 2 diabetes mellitus (T2DM) with or without sudomotor dysfunction (evaluated
      by the Neuropad test). We included 36 T2DM patients with sudomotor dysfunction
      (group A: mean age 63.1 +/- 2.6 years) and 40 age-, gender-, renal function- and
      T2DM duration-matched patients without sudomotor dysfunction (group B: mean age
      62.1 +/- 3.1 years). SUA was significantly higher in group A (P < 0.001). There
      was a significant correlation between SUA and Neuropad time to colour change in
      both groups (group A: r(s) = 0.819, P < 0.001; group B: r(s) = 0.774, P < 0.001).
      There was also a significant positive correlation between SUA and CRP in both
      groups (group A: r(s) = 0.947, P < 0.001; group B: r(s) = 0.848, P < 0.001). In
      conclusion, SUA levels were higher in T2DM patients with sudomotor dysfunction
      than those without this complication. The potential role of SUA in sudomotor
      dysfunction merits further study.

PMID- 21941528
TI  - Dysfunctional endothelial progenitor cells in metabolic syndrome.
AB  - The metabolic syndrome (MetS) is highly prevalent and confers an increased risk
      of diabetes and cardiovascular disease. A key early event in atherosclerosis is
      endothelial dysfunction. Numerous groups have reported endothelial dysfunction in
      MetS. However, the measurement of endothelial function is far from optimum. There
      has been much interest recently in a subtype of progenitor cells, termed
      endothelial progenitor cells (EPCs), that can circulate, proliferate, and
      dfferentiate into mature endothelial cells. EPCs can be characterized by the
      assessment of surface markers, CD34 and vascular endothelial growth factor
      receptor-2, VEGFR-2 (KDR). The CD34(+)KDR(+) phenotype has been demonstrated to
      be an independent predictor of cardiovascular outcomes. MetS patients without
      diabetes or cardiovascular diseases have decreased EPC number and functionality
      as evidenced by decreased numbers of colony forming units, decreased adhesion and
      migration, and decreased tubule formation. Strategies that have been shown to
      upregulate and enhance EPC number and functionality include statins, angiotensin
      converting enzyme inhibitors, angiotensin receptor blockers, and peroxisome
      proliferator-activating-receptor gamma agonists. Mechanisms by which they affect
      EPC number and functionality need to be studied. Thus, EPC number and/or
      functionality could emerge as novel cellular biomarkers of endothelial
      dysfunction and cardiovascular disease risk in MetS.

PMID- 21941529
TI  - Square or sine: finding a waveform with high success rate of eliciting SSVEP.
AB  - Steady state visual evoked potential (SSVEP) is the brain's natural electrical
      potential response for visual stimuli at specific frequencies. Using a visual
      stimulus flashing at some given frequency will entrain the SSVEP at the same
      frequency, thereby allowing determination of the subject's visual focus. The
      faster an SSVEP is identified, the higher information transmission rate the
      system achieves. Thus, an effective stimulus, defined as one with high success
      rate of eliciting SSVEP and high signal-noise ratio, is desired. Also,
      researchers observed that harmonic frequencies often appear in the SSVEP at a
      reduced magnitude. Are the harmonics in the SSVEP elicited by the fundamental
      stimulating frequency or by the artifacts of the stimuli? In this paper, we
      compare the SSVEP responses of three periodic stimuli: square wave (with
      different duty cycles), triangle wave, and sine wave to find an effective
      stimulus. We also demonstrate the connection between the strength of the
      harmonics in SSVEP and the type of stimulus.

PMID- 21941530
TI  - Comparison of classification methods for P300 brain-computer interface on
      disabled subjects.
AB  - We report on tests with a mind typing paradigm based on a P300 brain-computer
      interface (BCI) on a group of amyotrophic lateral sclerosis (ALS), middle
      cerebral artery (MCA) stroke, and subarachnoid hemorrhage (SAH) patients,
      suffering from motor and speech disabilities. We investigate the achieved typing
      accuracy given the individual patient's disorder, and how it correlates with the
      type of classifier used. We considered 7 types of classifiers, linear as well as
      nonlinear ones, and found that, overall, one type of linear classifier yielded a
      higher classification accuracy. In addition to the selection of the classifier,
      we also suggest and discuss a number of recommendations to be considered when
      building a P300-based typing system for disabled subjects.

PMID- 21941531
TI  - A preliminary test of measurement of joint angles and stride length with wireless
      inertial sensors for wearable gait evaluation system.
AB  - The purpose of this study is to develop wearable sensor system for gait
      evaluation using gyroscopes and accelerometers for application to rehabilitation,
      healthcare and so on. In this paper, simultaneous measurement of joint angles of
      lower limbs and stride length was tested with a prototype of wearable sensor
      system. The system measured the joint angles using the Kalman filter. Signals
      from the sensor attached on the foot were used in the stride length estimation
      detecting foot movement automatically. Joint angles of the lower limbs were
      measured with stable and reasonable accuracy compared to those values measured
      with optical motion measurement system with healthy subjects. It was expected
      that the stride length measurement with the wearable sensor system would be
      practical by realizing more stable measurement accuracy. Sensor attachment
      position was suggested not to affect significantly measurement of slow and normal
      speed movements in a test with the rigid body model. Joint angle patterns
      measured in 10 m walking with a healthy subject were similar to common patterns.
      High correlation between joint angles at some characteristic points and stride
      velocity were also found adequately. These results suggested that the wireless
      wearable inertial sensor system could detect characteristics of gait.

PMID- 21941532
TI  - Comparative Genomics in Perennial Ryegrass (Lolium perenne L.): Identification
      and Characterisation of an Orthologue for the Rice Plant Architecture-Controlling
      Gene OsABCG5.
AB  - Perennial ryegrass is an important pasture grass in temperate regions. As a
      forage biomass-generating species, plant architecture-related characters provide
      key objectives for breeding improvement. In silico comparative genomics analysis
      predicted colocation between a previously identified QTL for plant type (erect
      versus prostrate growth) and the ortholocus of the rice OsABCG5 gene (LpABCG5),
      as well as related QTLs in other Poaceae species. Sequencing of an LpABCG5
      containing BAC clone identified presence of a paralogue (LpABCG6) in the vicinity
      of the LpABCG5 locus, in addition to three other gene-like sequences. Comparative
      genomics involving five other 5 grass species (rice, Brachypodium, sorghum,
      maize, and foxtail millet) revealed conserved microsynteny in the ABCG5
      ortholocus-flanking region. Gene expression profiling and phylogenetic analysis
      suggested that the two paralogues are functionally distinct. Fourteen additional
      ABCG5 gene family members, which may interact with the LpABCG5 gene, were
      identified through sequencing of transcriptomes from perennial ryegrass leaf,
      anther, and pistils. A larger-scale phylogenetic analysis of the ABCG gene family
      suggested conservation between major branches of the Poaceae family. This study
      identified the LpABCG5 gene as a candidate for the plant type determinant,
      suggesting that manipulation of gene expression may provide valuable phenotypes
      for perennial ryegrass breeding.

PMID- 21941534
TI  - The long-term outcomes after radical prostatectomy of patients with pathologic
      Gleason 8-10 disease.
AB  - Background. We explored the long-term clinical outcomes including metastases-free
      survival and prostate cancer-specific survival (PCSS) in patients with pathologic
      Gleason 8-10 disease after radical prostatectomy (RP). Methods. We report on 91
      patients with PCSS data with a median followup of 8.2 years after RP performed
      between 1988 and 1997. Cox regression and Kaplan-Meier analysis were used to
      evaluate year of surgery, pathologic stage, and surgical margin status as
      predictors of PCSM. Results. Median age was 65 years (IQR: 61-9), and median PSA
      was 9.7 ng/ml (IQR: 6.1-13.4). Of all patients, 62 (68.9%) had stage T3 disease
      or higher, and 48 (52.7%) had a positive surgical margin. On multivariate
      analysis, none of the predictors were statistically significant. Of all patients,
      the predicted 10-year BCR-free survival, mets-free survival, and PCSS were 59%
      (CI: 53%-65%), 88% (CI: 84%-92%), and 94% (CI: 91%-97%), respectively.
      Conclusions. We have demonstrated that cancer control is durable even 10 years
      after RP in those with pathologic Gleason 8-10 disease. Although 40% will succumb
      to BCR, only 6% of patients died of their disease. These results support the use
      of RP for patients with high-risk localized prostate cancer.

PMID- 21941535
TI  - A case of definitive therapy for localised prostate cancer: report of a
      urological nightmare.
AB  - Radical prostatectomy, external beam radiotherapy and permanent brachytherapy are
      the most common treatment options for nonmetastatic localised adenocarcinoma of
      the prostate (PCa). Accurate pretherapeutic clinical staging is difficult, the
      number of positive cores after biopsy does not imperatively represent the
      extension of the cancer. Furthermore postoperative upgrading in Gleason score is
      frequently observed. Even in a localised setting a certain amount of patients
      with organ-confined PCa will develop biochemical progression. In case of a rise
      in PSA level after radiation the majority of patients will receive androgen
      deprivation therapy what must be considered as palliative. If local or systemic
      progressive disease is associated with evolving neuroendocrine differentiation
      hormonal manipulation is increasingly ineffective; radiotherapy and systemic
      chemotherapy with a platinum agent and etoposide are recommended. In case of
      local progression complications such as pelvic pain, gross haematuria,
      infravesical obstruction and rectal invasion with obstruction and consecutive
      ileus can possibly occur. In this situation palliative radical surgery is a
      therapy option especially in the absence of distant metastases. A case with local
      and later systemic progression after permanent brachytherapy is presented here.

PMID- 21941533
TI  - Oxidative stress in neurodegeneration.
AB  - It has been demonstrated that oxidative stress has a ubiquitous role in
      neurodegenerative diseases. Major source of oxidative stress due to reactive
      oxygen species (ROS) is related to mitochondria as an endogenous source. Although
      there is ample evidence from tissues of patients with neurodegenerative disorders
      of morphological, biochemical, and molecular abnormalities in mitochondria, it is
      still not very clear whether the oxidative stress itself contributes to the onset
      of neurodegeneration or it is part of the neurodegenerative process as secondary
      manifestation. This paper begins with an overview of how oxidative stress occurs,
      discussing various oxidants and antioxidants, and role of oxidative stress in
      diseases in general. It highlights the role of oxidative stress in
      neurodegenerative diseases like Alzheimer's, Parkinson's, and Huntington's
      diseases and amyotrophic lateral sclerosis. The last part of the paper describes
      the role of oxidative stress causing deregulation of cyclin-dependent kinase 5
      (Cdk5) hyperactivity associated with neurodegeneration.

PMID- 21941536
TI  - The anatomy of teleneurosurgery in china.
AB  - With its huge population and vast territory, China faces a great challenge in
      providing modern advanced health care services to all parts of the country. The
      advances of information communication technologies (ICTs) and the advent of
      internet have revolutionised the means in the delivery of healthcare via
      telemedicine to remote and underserved populations, which to a certain extent has
      been very well exploited in China, especially where 70% peasants residing in the
      rural areas. This paper reviews the latest development in telemedicine
      infrastructure in China with the focus on the development of teleneurosurgery,
      drawing from the results gained from a 3-year networking project between Europe
      and China on telemedicine (TIME, 2005-2007) funded by European Commission under
      Asia ICT programme, with an aim to shape up envisages of future medical care in
      China. Comparison with its counterparts in Europe is also addressed.

PMID- 21941537
TI  - MRSA: A Challenge to Norwegian Nursing Home Personnel.
AB  - In Norway, methicillin-resistant Staphylococcus aureus (MRSA) is increasing in
      primary healthcare, associated with imported cases and outbreaks in long-term
      care. According to Norwegian national guidelines, MRSA-exposed healthcare workers
      (HCWs) and patients are tested. Carriage of MRSA leads to exclusion from work in
      healthcare institutions. In this study, 388 staff members in 42 nursing homes in
      Oslo County responded to questions about personal experience with MRSA and of own
      attitudes to challenges associated with the control and treatment of MRSA
      patients. Half (52%) of the nursing staff were concerned of becoming infected
      with MRSA and the consequences of this would be for own social life, family,
      economy, and work restriction. The concern was associated with risk factors like
      old buildings not suitable for modern infection control work, low staffing rate
      (70% without specific training in healthcare and 32% without formal healthcare
      education), defective cleaning and decolonization, and lack of formal routines
      and capacity for isolation of MRSA patients. Since the Norwegian MRSA guideline
      permits patients with persistent MRSA infections to move freely around in nursing
      homes, the anxiety of the staff to become infected and excluded from job was
      real.

PMID- 21941538
TI  - CsmA Protein is Associated with BChl a in the Baseplate Subantenna of Chlorosomes
      of the Photosynthetic Green Filamentous Bacterium Oscillochloris trichoides
      belonging to the Family Oscillochloridaceae.
AB  - The baseplate subantenna in chlorosomes of green anoxygenic photosynthetic
      bacteria, belonging to the families Chloroflexaceae and Chlorobiaceae, is known
      to represent a complex of bacteriochlorophyll (BChl) a with the ~6 kDa CsmA
      proteins. Earlier, we showed the existence of a similar BChl a subantenna in
      chlorosomes of the photosynthetic green bacterium Oscillochloris trichoides,
      member of Oscillochloridaceae, the third family of green photosynthetic bacteria.
      However, this BChl a subantenna was not visually identified in absorption spectra
      of isolated Osc. trichoides chlorosomes in contrast to those of Chloroflexaceae
      and Chlorobiaceae. In this work, using room and low-temperature absorbance and
      fluorescence spectroscopy and sodium dodecyl sulfate polyacrylamide gel
      electrophoresis analysis of alkaline-treated and untreated chlorosomes of Osc.
      trichoides, we showed that the baseplate BChl a subantenna does exist in
      Oscillochloridaceae chlorosomes as a complex of BChl a with the 5.7 kDa CsmA
      protein. The present results support the idea that the baseplate subantenna,
      representing a complex of BChl a with a ~6 kDa CsmA protein, is a universal
      interface between the BChl c subantenna of chlorosomes and the nearest light
      harvesting BChl a subantenna in all three known families of green anoxygenic
      photosynthetic bacteria.

PMID- 21941539
TI  - Computational Design of a DNA- and Fc-Binding Fusion Protein.
AB  - Computational design of novel proteins with well-defined functions is an ongoing
      topic in computational biology. In this work, we generated and optimized a new
      synthetic fusion protein using an evolutionary approach. The optimization was
      guided by directed evolution based on hydrophobicity scores, molecular weight,
      and secondary structure predictions. Several methods were used to refine the
      models built from the resulting sequences. We have successfully combined two
      unrelated naturally occurring binding sites, the immunoglobin Fc-binding site of
      the Z domain and the DNA-binding motif of MyoD bHLH, into a novel stable protein.

PMID- 21941540
TI  - Lead-binding proteins: a review.
AB  - Lead-binding proteins are a series of low molecular weight proteins, analogous to
      metallothionein, which segregate lead in a nontoxic form in several organs
      (kidney, brain, lung, liver, erythrocyte). Whether the lead-binding proteins in
      every organ are identical or different remains to be determined. In the
      erythrocyte, delta-aminolevulinic acid dehydratase (ALAD) isoforms have commanded
      the greatest attention as proteins and enzymes that are both inhibitable and
      inducible by lead. ALAD-2, although it binds lead to a greater degree than ALAD
      1, appears to bind lead in a less toxic form. What may be of greater significance
      is that a low molecular weight lead-binding protein, approximately 10 kDa,
      appears in the erythrocyte once blood lead exceeds 39 MUg/dL and eventually
      surpasses the lead-binding capacity of ALAD. In brain and kidney of
      environmentally exposed humans and animals, a cytoplasmic lead-binding protein
      has been identified as thymosin beta4, a 5 kDa protein. In kidney, but not brain,
      another lead-binding protein has been identified as acyl-CoA binding protein, a 9
      kDa protein. Each of these proteins, when coincubated with liver ALAD and
      titrated with lead, diminishes the inhibition of ALAD by lead, verifying their
      ability to segregate lead in a nontoxic form.

PMID- 21941542
TI  - Exposure of the main italian river basin to pharmaceuticals.
AB  - This study give a preliminary survey of pharmaceutical contamination and
      accumulation in surface waters and sediments along the river Po basin (74,000
      km(2), the largest in Italy), a strategic region for the Italian economy: it
      collects sewage from a vast industrialized area of Italy (Autorita di Baciono del
      fiume Po, 2006, 2009). 10 pharmaceuticals (atenolol, propanolol, metoprolol,
      nimesulide, furosemide, carbamazepine, ranitidine, metronidazole, paracetamol,
      and atorvastatin) from several therapeutic classes were searched in 54 sampling
      points along the river Po from the source to the delta, and at the mouth of its
      major effluents. In water samples were found pharmaceuticals in the range of 0.38
      0.001 MUg/L, except for furosemide (max conc. 0.605 MUg/L), paracetamol (max
      conc. 3.59 MUg/L), metoprolol (never detected) and for atenolol (not analysed).
      In sediment samples, only paracetamol was not detected, while the others were
      generally found in the range of 0.4-0.02 MUg/kg ww with high concentrations for
      atenolol (max conc. 284 MUg/kg ww) and furosemide (max conc. 98.4 MUg/kg ww). The
      findings confirm also STPs as point sources of contamination. Despite of the much
      evidence for the adverse effects of pharmaceuticals in the aquatic environment,
      the observed low levels cannot be considered to pose a serious risk to human
      health; further studies are necessary for a comprehensive risk assessment.

PMID- 21941541
TI  - Biochemical factors modulating cellular neurotoxicity of methylmercury.
AB  - Methylmercury (MeHg), an environmental toxicant primarily found in fish and
      seafood, poses a dilemma to both consumers and regulatory authorities, given the
      nutritional benefits of fish consumption versus the possible adverse neurological
      damage. Several studies have shown that MeHg toxicity is influenced by a number
      of biochemical factors, such as glutathione (GSH), fatty acids, vitamins, and
      essential elements, but the cellular mechanisms underlying these complex
      interactions have not yet been fully elucidated. The objective of this paper is
      to outline the cellular response to dietary nutrients, as well as to describe the
      neurotoxic exposures to MeHg. In order to determine the cellular mechanism(s) of
      toxicity, the effect of pretreatment with biochemical factors (e.g., N-acetyl
      cysteine, (NAC); diethyl maleate, (DEM); docosahexaenoic acid, (DHA);
      selenomethionine, SeM; Trolox) and MeHg treatment on intercellular antioxidant
      status, MeHg content, and other endpoints was evaluated. This paper emphasizes
      that the protection against oxidative stress offered by these biochemical factors
      is among one of the major mechanisms responsible for conferring neuroprotection.
      It is therefore critical to ascertain the cellular mechanisms associated with
      various dietary nutrients as well as to determine the potential effects of
      neurotoxic exposures for accurately assessing the risks and benefits associated
      with fish consumption.

PMID- 21941543
TI  - Retargeting Clostridium difficile Toxin B to Neuronal Cells as a Potential
      Vehicle for Cytosolic Delivery of Therapeutic Biomolecules to Treat Botulism.
AB  - Botulinum neurotoxins (BoNTs) deliver a protease to neurons which can cause a
      flaccid paralysis called botulism. Development of botulism antidotes will require
      neuronal delivery of agents that inhibit or destroy the BoNT protease. Here, we
      investigated the potential of engineering Clostridium difficile toxin B (TcdB) as
      a neuronal delivery vehicle by testing two recombinant TcdB chimeras. For AGT
      TcdB chimera, an alkyltransferase (AGT) was appended to the N-terminal
      glucosyltransferase (GT) of TcdB. Recombinant AGT-TcdB had alkyltransferase
      activity, and the chimera was nearly as toxic to Vero cells as wild-type TcdB,
      suggesting efficient cytosolic delivery of the AGT/GT fusion. For AGT-TcdB-BoNT/A
      Hc, the receptor-binding domain (RBD) of TcdB was replaced by the equivalent RBD
      from BoNT/A (BoNT/A-Hc). AGT-TcdB-BoNT/A-Hc was >25-fold more toxic to neuronal
      cells and >25-fold less toxic to Vero cells than AGT-TcdB. Thus, TcdB can be
      engineered for cytosolic delivery of biomolecules and improved targeting of
      neuronal cells.

PMID- 21941544
TI  - Therapeutic use of botulinum toxin in neurorehabilitation.
AB  - The botulinum toxins (BTX), type A and type B by blocking vesicle acetylcholine
      release at neuro-muscular and neuro-secretory junctions can result efficacious
      therapeutic agents for the treatment of numerous disorders in patients requiring
      neuro-rehabilitative intervention. Its use for the reduction of focal spasticity
      following stroke, brain injury, and cerebral palsy is provided. Although the
      reduction of spasticity is widely demonstrated with BTX type A injection, its
      impact on the improvement of dexterity and functional outcome remains
      controversial. The use of BTX for the rehabilitation of children with obstetrical
      brachial plexus palsy and in treating sialorrhea which can complicate the course
      of some severe neurological diseases such as amyotrophic lateral sclerosis and
      Parkinson's disease is also addressed. Adverse events and neutralizing antibodies
      formation after repeated BTX injections can occur. Since impaired neurological
      persons can have complex disabling feature, BTX treatment should be viewed as
      adjunct measure to other rehabilitative strategies that are based on the
      individual's residual ability and competence and targeted to achieve the best
      functional recovery. BTX therapy has high cost and transient effect, but its
      benefits outweigh these disadvantages. Future studies must clarify if this agent
      alone or adjunctive to other rehabilitative procedures works best on functional
      outcome.

PMID- 21941545
TI  - Use of Clostridium perfringens Enterotoxin and the Enterotoxin Receptor-Binding
      Domain (C-CPE) for Cancer Treatment: Opportunities and Challenges.
AB  - Clostridium perfringens enterotoxin (CPE) causes the symptoms associated with
      several common gastrointestinal diseases. CPE is a 35 kDa polypeptide consisting
      of three structured domains, that is, C-terminal domain I (responsible for
      receptor binding), domain II (responsible for oligomerization and membrane
      insertion), and domain III (which may participate in physical changes when the
      CPE protein inserts into membranes). Native CPE binds to claudin receptors, which
      are components of the tight junction. The bound toxin then assembles into a
      hexameric prepore on the membrane surface, prior to the insertion of this
      oligomer into membranes to form an active pore. The toxin is especially lethal
      for cells expressing large amounts of claudin-3 or -4, which includes many cancer
      cells. Initial studies suggest that native CPE has potential usefulness for
      treating several cancers where claudin CPE receptors are overexpressed. However,
      some challenges with immunogenicity, toxicity, and (possibly) the development of
      resistance may need to be overcome. An alternative approach now being explored is
      to utilize C-CPE, which corresponds approximately to receptor binding domain I,
      to enhance paracellular permeability and delivery of chemotherapeutic agents
      against cancer cells. Alternatively, C-CPE fusion proteins may prove superior to
      use of native CPE for cancer treatment. Finally, C-CPE may have application for
      other medical treatments, including vaccination or increasing drug absorption.
      The coming years should witness increasing exploitation of this otherwise
      formidable toxin.

PMID- 21941548
TI  - The Characteristics of Vascular Growth in VX2 Tumor Measured by MRI and Micro-CT.
AB  - Blood supply is crucial for rapid growth of a malignant tumor; medical imaging
      can play an important role in evaluating the vascular characterstics of tumors.
      Magnetic resonance imaging (MRI) and micro-computed tomography (CT) are able to
      detect tumors and measure blood volumes of microcirculation in tissue. In this
      study, we used MR imaging and micro-CT to assess the microcirculation in a VX2
      tumor model in rabbits. MRI characterization was performed using the
      intravascular contrast agent Clariscan (NC100150-Injection); micro-CT with
      Microfil was used to directly depict blood vessels with diameters as low as 17 um
      in tissue. Relative blood volume fraction (rBVF) in the tumor rim and blood
      vessel density (rBVD) over the whole tumor was calculated using the two imaging
      methods. Our study indicates that rBVF is negatively related to the volume of the
      tumor measured by ultrasound (R = 0.90). rBVF in the tissue of a VX2 tumor
      measured by MRI in vivo was qualitatively consistent with the rBVD demonstrated
      by micro-CT in vitro (R = 0.97). The good correlation between the two methods
      indicates that MRI studies are potentially valuable for assessing characteristics
      or tumor vascularity and for assessing response to therapy noninvasively.

PMID- 21941549
TI  - In vitro repair of fractured fiber-reinforced cusp-replacing composite
      restorations.
AB  - Objective. To assess fracture resistance and failure mode of repaired fiber
      reinforced composite (FRC) cusp-replacing restorations. Methods. Sixteen
      extracted human premolars with fractured cusp-replacing woven (Group (A)) or
      unidirectional (Group (B)) FRC restorations from a previous loading experiment
      were repaired with resin composite and loaded to fracture. Results. Differences
      in fracture loads between groups were not statistically significant (P = 0.34).
      Fracture loads of repaired specimens were significantly lower than those of
      original specimens (P = 0.02 for Group (A) and P < 0.001 for Group (B)). Majority
      of specimens showed failure along the repaired surface. In Group (B) 89% of
      specimens showed intact tooth substrate after restoration fracture, while this
      was 28% in Group (A) (P = 0.04). Conclusion. Fractured cusp-replacing FRC
      restorations that are repaired with resin composite show about half of fracture
      resistance of original restorations. Mode of failure with a base of
      unidirectional fibers is predominantly adhesive.

PMID- 21941546
TI  - Pathobiology and chemoprevention of bladder cancer.
AB  - Our understanding of the pathogenesis of bladder cancer has improved considerably
      over the past decade. Translating these novel pathobiological discoveries into
      therapies, prevention, or strategies to manage patients who are suspected to have
      or who have been diagnosed with bladder cancer is the ultimate goal. In
      particular, the chemoprevention of bladder cancer development is important, since
      urothelial cancer frequently recurs, even if the primary cancer is completely
      removed. The numerous alterations of both oncogenes and tumor suppressor genes
      that have been implicated in bladder carcinogenesis represent novel targets for
      therapy and prevention. In addition, knowledge about these genetic alterations
      will help provide a better understanding of the biological significance of
      preneoplastic lesions of bladder cancer. Animal models for investigating bladder
      cancer development and prevention can also be developed based on these
      alterations. This paper summarizes the results of recent preclinical and clinical
      chemoprevention studies and discusses screening for bladder cancer.

PMID- 21941550
TI  - Resin-bonded fiber-reinforced composite for direct replacement of missing
      anterior teeth: a clinical report.
AB  - Missing anterior teeth is of serious concern in the social life of a patient in
      most of societies. While conventional fixed partial dentures and implant
      supported restorations may often be the treatment of choice, fiber-reinforced
      composite (FRC) resins offer a conservative, fast, and cost-effective alternative
      for single and multiple teeth replacement. This paper presents two cases where
      FRC technology was successfully used to restore anterior edentulous areas in
      terms of esthetic values and functionality.

PMID- 21941551
TI  - Preparation, physical-chemical characterization, and cytocompatibility of
      polymeric calcium phosphate cements.
AB  - Aim. Physicochemical mechanical and in vitro biological properties of novel
      formulations of polymeric calcium phosphate cements (CPCs) were investigated.
      Methods. Monocalcium phosphate, calcium oxide, and synthetic hydroxyapatite were
      combined with either modified polyacrylic acid, light activated polyalkenoic
      acid, or polymethyl vinyl ether maleic acid to obtain Types I, II, and III CPCs.
      Setting time, compressive and diametral strength of CPCs was compared with zinc
      polycarboxylate cement (control). Specimens were characterized using X-ray
      diffraction, scanning electron microscopy, and infrared spectroscopy. In vitro
      cytotoxicity of CPCs and control was assessed. Results. X-ray diffraction
      analysis showed hydroxyapatite, monetite, and brushite. Acid-base reaction was
      confirmed by the appearance of stretching peaks in IR spectra of set cements. SEM
      revealed rod-like crystals and platy crystals. Setting time of cements was 5-12
      min. Type III showed significantly higher strength values compared to control.
      Type III yielded high biocompatibility. Conclusions. Type III CPCs show promise
      for dental applications.

PMID- 21941552
TI  - The red blood cell as a gender-associated biomarker in metabolic syndrome: a
      pilot study.
AB  - In the present pilot study (56 patients), some red blood cell parameters in
      samples from patients with metabolic syndrome and subclinical atherosclerosis,
      but without any sign of coronary artery disease, have been analyzed. The main
      goal of this work was to determine, in this preclinical state, new peripheral
      gender-associated bioindicators of possible diagnostic or prognostic value. In
      particular, three different "indicators" of red blood cell injury and aging have
      been evaluated: glycophorin A, CD47, and phosphatidylserine externalization.
      Interestingly, all these determinants appeared significantly modified and
      displayed gender differences. These findings could provide novel and useful hints
      in the research for gender-based real-time bioindicators in the progression of
      metabolic syndrome towards coronary artery disease. Further, more extensive
      studies are, however, necessary in order to validate these findings.

PMID- 21941547
TI  - Integrin-mediated cell-matrix interaction in physiological and pathological blood
      vessel formation.
AB  - Physiological as well as pathological blood vessel formation are fundamentally
      dependent on cell-matrix interaction. Integrins, a family of major cell adhesion
      receptors, play a pivotal role in development, maintenance, and remodeling of the
      vasculature. Cell migration, invasion, and remodeling of the extracellular matrix
      (ECM) are integrin-regulated processes, and the expression of certain integrins
      also correlates with tumor progression. Recent advances in the understanding of
      how integrins are involved in the regulation of blood vessel formation and
      remodeling during tumor progression are highlighted. The increasing knowledge of
      integrin function at the molecular level, together with the growing repertoire of
      integrin inhibitors which allow their selective pharmacological manipulation,
      makes integrins suited as potential diagnostic markers and therapeutic targets.

PMID- 21941553
TI  - The Role of BCL2 Family of Apoptosis Regulator Proteins in Acute and Chronic
      Leukemias.
AB  - The disturbance of apoptosis molecular signaling pathways is involved in
      carcinogenesis. BCL2 family of proteins is the hallmark of apoptosis regulation.
      In the last decade, new members of BCL2 gene family were discovered and cloned
      and were found to be differentially expressed in many types of cancer. BCL2
      protein family, through its role in regulation of apoptotic pathways, is possibly
      related to cancer pathophysiology and resistance to conventional chemotherapy. It
      is well known that leukemias are haematopoietic malignancies characterized by
      biological diversity, varied cytogenetics, different immunophenotype profiles,
      and diverse outcome. Current research focuses on the prognostic impact and
      specific role of these proteins in the pathogenesis of leukemias. The
      understanding of the molecular pathways that participate in the biology of
      leukemias may lead to the design of new therapies which may improve patients'
      survival. In the present paper, we describe current knowledge on the role of BCL2
      apoptosis regulator proteins in acute and chronic leukemias.

PMID- 21941554
TI  - Extracellular NM23 Protein as a Therapeutic Target for Hematologic Malignancies.
AB  - An elevated serum level of NM23-H1 protein is a poor prognostic factor in
      patients with various hematologic malignancies. The extracellular NM23-H1 protein
      promotes the in vitro growth and survival of acute myelogenous leukemia (AML)
      cells and inversely inhibits the in vitro survival of normal peripheral blood
      monocytes in primary culture at concentrations equivalent to the levels found in
      the serum of AML patients. The growth and survival promoting activity to AML
      cells is associated with cytokine production and activation of mitogen-activated
      protein kinases (MAPKs) and signal transducers and activators of transcription
      (STAT) signaling pathways. Inhibitors specific for MAPK signaling pathways
      inhibit the growth/survival-promoting activity of NM23-H1. These findings
      indicate a novel biological action of extracellular NM23-H1 and its association
      with poor prognosis. These results suggest an important role of extracellular
      NM23-H1 in the malignant progression of leukemia and a potential therapeutic
      target for these malignancies.

PMID- 21941555
TI  - The many faces of interleukin-6: the role of IL-6 in inflammation, vasculopathy,
      and fibrosis in systemic sclerosis.
AB  - Interleukin-6 is currently attracting significant interest as a potential
      therapeutic target in systemic sclerosis (SSc). In this paper, the biology of
      interleukin-6 is reviewed, and the evidence for interleukin-6 dysregulation in
      SSc is explored. The role of inteleukin-6 classical and trans signalling pathways
      in SSc relevant phenomena such as chronic inflammation, autoimmunity, endothelial
      cell dysfunction, and fibrogenesis is discussed. The existing evidence that
      interventions designed to block interleukin-6 signalling are of therapeutic
      relevance in SSc is evaluated.

PMID- 21941556
TI  - Are costs of robot-assisted surgery warranted for gynecological procedures?
AB  - The exponential use of robotic surgery is not the result of evidence-based
      benefits but mainly driven by the manufacturers, patients and enthusiastic
      surgeons. The present review of the literature shows that robot-assisted surgery
      is consistently more expensive than video-laparoscopy and in many cases open
      surgery. The average additional variable cost for gynecological procedures was
      about 1600 USD, rising to more than 3000 USD when the amortized cost of the robot
      itself was included. Generally most robotic and laparoscopic procedures have less
      short-term morbidity, blood loss, intensive care unit, and hospital stay than
      open surgery. Up to now no major consistent differences have been found between
      robot-assisted and classic video-assisted procedures for these factors. No
      comparative data are available on long-term morbidity and oncologic outcome after
      open, robotic, and laparoscopic gynecologic surgery. It seems that currently only
      for very complex surgical procedures, such as cardiac surgery, the costs of
      robotics can be competitive to open surgical procedures. In order to stay viable,
      robotic programs will need to pay for themselves on a per case basis and the
      costs of robotic surgery will have to be reduced.

PMID- 21941557
TI  - Comparison of nulliparas undergoing cesarean section in first and second stages
      of labour: a prospective study in a tertiary teaching hospital.
AB  - Objective. We performed a prospective observational audit study to compare
      neonatal and maternal outcomes of the primary cesarean sections performed in
      first stage versus second stage of labour. Methods. One thousand three hundred
      and eighty-nine nullipara women who had undergone cesarean section in a tertiary
      teaching hospital between February 1, 2009 and January 31, 2010 were included in
      the study. Primary maternal outcomes of interest were uterine atonia, transfusion
      requirement, urinary system injury, requirement for hysterectomy, and duration of
      hospital stay. Results. A total of 1389 women underwent cesarean section at this
      12 month time period. Of these 1389 cesarean sections, 1271 were in the first
      stage of the labour and 171 were in the second stage of the labour. Urinary
      injuries, transfusion requirement, and uterine atonia hysterectomy were
      significantly more frequent in women who underwent cesarean section in the second
      stage of the labour compared to women undergoing cesarean section in the first
      stage of the labour. Conclusion. Cesarean section in the second stage of the
      labour is associated with increased maternal and neonatal morbidities. Special
      attention is required to the patients undergoing cesarean section in the second
      stage of the labour.

PMID- 21941559
TI  - Ossification of transverse ligament of atlas causing cervical myelopathy: a case
      report and review of the literature.
AB  - A case of ossification of transverse ligament of atlas (TLA) is reported. A 76
      year-old female suffered from a transverse type myelopathy was successfully
      treated by posterior decompression. Dynamic lateral plain radiographs showed
      irreducible atlantoaxial subluxation (AAS). A computed tomogram revealed ossified
      mass compatible to ossification of TLA. Coalition of the atlantooccipital joints
      and osteoarthritis of the atlantoaxial joints with degenerated dens was also
      revealed. Magnetic resonance imaging showed compressed spinal cord at C1 level by
      the ossification of TLA and AAS. We suggest a mechanism of ossification of TLA as
      follows: hypertrophied dens and stress to the atlantoaxial joints caused by
      coalition of atlantooccipital joints could make forward shift of atlas leading to
      irreducible AAS, and continuous tension given to TLA from irreducible AAS would
      result in hypertrophied and ossification of TLA.

PMID- 21941558
TI  - Pelvic organ distribution of mesenchymal stem cells injected intravenously after
      simulated childbirth injury in female rats.
AB  - The local route of stem cell administration utilized presently in clinical trials
      for stress incontinence may not take full advantage of the capabilities of these
      cells. The goal of this study was to evaluate if intravenously injected
      mesenchymal stem cells (MSCs) home to pelvic organs after simulated childbirth
      injury in a rat model. Female rats underwent either vaginal distension (VD) or
      sham VD. All rats received 2 million GFP-labeled MSCs intravenously 1 hour after
      injury. Four or 10 days later pelvic organs and muscles were imaged for
      visualization of GFP-positive cells. Significantly more MSCs home to the urethra,
      vagina, rectum, and levator ani muscle 4 days after VD than after sham VD. MSCs
      were present 10 days after injection but GFP intensity had decreased. This study
      provides basic science evidence that intravenous administration of MSCs could
      provide an effective route for cell-based therapy to facilitate repair after
      injury and treat stress incontinence.

PMID- 21941560
TI  - Rapidly growing chondroid syringoma of the external auditory canal: report of a
      rare case.
AB  - Introduction. Chondroid syrinoma of the external auditory canal is an extremely
      rare benign neoplasm representing the cutaneous counterpart of pleomorphic
      adenoma of salivary glands. Less than 35 cases have been reported in the
      international literature. Case Presentation. We report a case of a 34-year-old
      male in whom a rapidly growing, well-circumscribed tumor arising from the
      external auditory canal was presented. Otoscopy revealed a smooth, nontender
      lesion covered by normal skin that almost obstructs the external auditory meatus.
      MRI was performed to define the extension of the lesion. It confirmed the
      presence of a 1.5 * 0.8 cm T2 high-signal intensity lesion in the superior and
      posterior wall of EAC without signs of bone erosion. The patient underwent
      complete resection of the tumor. The diagnosis was confirmed by histopathologic
      examination. Conclusion. Although chondroid syringoma is extremely rare, it
      should always be considered in the differential diagnosis of an aural polyp.
      Chondroid syringomas are usually asymptomatic, slow-growing, single benign tumors
      in subcutaneous or intradermal location. In our case, the new information is that
      this benign tumor could present also as a rapidly growing lesion, arising the
      suspicion for malignancy.

PMID- 21941561
TI  - Coexistence of vulvar dowling-degos disease and seborrhoeic keratosis.
AB  - Dowling-Degos disease is a rare autosomal dominant inherited pigmentary disorder,
      mostly confined to the flexures. Diagnosis is established based on the clinical
      and histopathological correlation. The authors describe the clinical case of a
      female patient with vulvar involvement and multiple seborrhoeic keratoses on her
      face, neck, and upper trunk. Major and minor clinical manifestations of Dowling
      Degos disease are discussed, with particular emphasis on the genital location of
      the lesions, which is a rare finding. Also the presence of seborrhoeic keratosis
      is discussed as a coincidence or a true-associated phenomenon.

PMID- 21941562
TI  - Meniscal Regeneration: A Cause of Persisting Pain following Total Knee
      Arthroplasty.
AB  - Many patients have persisting knee pain following total knee arthroplasty. We
      report the unusual case of a patient whose chronic lateral and medial knee pain
      were caused by entrapped regenerated meniscal tissue. This was diagnosed and
      successfully treated by arthroscopic debridement.

PMID- 21941563
TI  - Pedunculated angiomyofibroblastoma of the vulva: case report and review of the
      literature.
AB  - Angiomyofibroblastoma (AMFB) is a rare benign mesenchymal tumour that occurs
      almost exclusively in the vulvovaginal region of women but can also occur
      occasionally in the inguinoscrotal region of men. It is a well-circumscribed
      lesion that clinically is often thought to represent a Bartholin's gland cyst and
      usually does not form a pedunculated mass. To our knowledge, only five cases of
      vulvar AMFB with pedunculated mass have been reported in the English literature
      and all cases involving the labia majora and middle-aged women. We report the
      first case of pedunculated AMFB of the vulva occurring in a young woman of 21
      years old and involving the left labia minora. After excluding the most common
      diseases, pedunculated AMFB should be part of differential diagnosis in the
      workup of any pedunculated vulvar mass even in young women with a lesion
      involving the labia minora. We reviewed the literature and summarized all
      reported cases.

PMID- 21941564
TI  - Transcription factor lbx1 expression in mouse embryonic stem cell-derived
      phenotypes.
AB  - Transcription factor Lbx1 is known to play a role in the migration of muscle
      progenitor cells in limb buds and also in neuronal determination processes. In
      addition, involvement of Lbx1 in cardiac neural crest-related cardiogenesis was
      postulated. Here, we used mouse embryonic stem (ES) cells which have the capacity
      to develop into cells of all three primary germ layers. During in vitro
      differentiation, ES cells recapitulate cellular developmental processes and gene
      expression patterns of early embryogenesis. Transcript analysis revealed a
      significant upregulation of Lbx1 at the progenitor cell stage. Immunofluorescence
      staining confirmed the expression of Lbx1 in skeletal muscle cell progenitors and
      GABAergic neurons. To verify the presence of Lbx1 in cardiac cells, triple
      immunocytochemistry of ES cell-derived cardiomyocytes and a quantification assay
      were performed at different developmental stages. Colabeling of Lbx1 and cardiac
      specific markers troponin T, alpha-actinin, GATA4, and Nkx2.5 suggested a
      potential role in early myocardial development.

PMID- 21941565
TI  - Comparison of Gene Expression in Human Embryonic Stem Cells, hESC-Derived
      Mesenchymal Stem Cells and Human Mesenchymal Stem Cells.
AB  - We present a strategy to identify developmental/differentiation and plasma
      membrane marker genes of the most primitive human Mesenchymal Stem Cells (hMSCs).
      Using sensitive and quantitative TaqMan Low Density Arrays (TLDA) methodology, we
      compared the expression of 381 genes in human Embryonic Stem Cells (hESCs), hESC
      derived MSCs (hES-MSCs), and hMSCs. Analysis of differentiation genes indicated
      that hES-MSCs express the sarcomeric muscle lineage in addition to the classical
      mesenchymal lineages, suggesting they are more primitive than hMSCs. Transcript
      analysis of membrane antigens suggests that IL1R1(low), BMPR1B(low), FLT4(low),
      LRRC32(low), and CD34 may be good candidates for the detection and isolation of
      the most primitive hMSCs. The expression in hMSCs of cytokine genes, such as IL6,
      IL8, or FLT3LG, without expression of the corresponding receptor, suggests a role
      for these cytokines in the paracrine control of stem cell niches. Our database
      may be shared with other laboratories in order to explore the considerable
      clinical potential of hES-MSCs, which appear to represent an intermediate
      developmental stage between hESCs and hMSCs.

PMID- 21941566
TI  - An inducible expression system of the calcium-activated potassium channel 4 to
      study the differential impact on embryonic stem cells.
AB  - Rationale. The family of calcium-activated potassium channels consists of four
      members with varying biological functions and conductances. Besides membrane
      potential modulation, SK channels have been found to be involved in cardiac
      pacemaker cell development from ES cells and morphological shaping of neural stem
      cells. Objective. Distinct SK channel subtype expression in ES cells might
      elucidate their precise impact during cardiac development. We chose SK channel
      subtype 4 as a potential candidate influencing embryonic stem cell
      differentiation. Methods. We generated a doxycycline inducible mouse ES cell line
      via targeted homologous recombination of a cassette expressing a bicistronic
      construct encoding SK4 and a fluorophore from the murine HPRT locus. Conclusion.
      We characterized the mouse ES cell line iSK4-AcGFP. The cassette is readily
      expressed under the control of doxycycline, and the overexpression of SK4 led to
      an increase in cardiac and pacemaker cell differentiation thereby serving as a
      unique tool to characterize the cell biological variances due to specific SK
      channel overexpression.

PMID- 21941567
TI  - Field and Laboratory Evaluation of Bioefficacy of an Insect Growth Regulator
      (Dimilin) as a Larvicide against Mosquito and Housefly Larvae.
AB  - The inhibitory function of Dimilin (Diflubenzuron), mostly a chitin synthesis
      regulator, on the ecdysis of mosquitoes (Anopheles gambiae s.l., Culex
      quinquefasciatus) and housefly was evaluated in the field and in laboratory.
      Three formulations of Diflubenzuron were evaluated in this study: Dimilin,
      Wettable powder (25%), Dimilin granules (2%), and Dimilin tablets (2%). The
      laboratory and field evaluation used different rates of concentrations of these
      formulations. Generally, at higher dosages larvae developments, eggs hatchability
      and pupation were impossible. The development of mosquitoes was significantly
      higher in control while highly depressed in different dosages of treatment in
      both laboratory and field experiments. In houseflies, the adult population
      decreased sharply after treatment of their breeding sites while pupae mortality
      was noticed to be high in laboratory-treated samples. Dimilin could be opted as
      one of the choice of the larval control chemicals to be incorporated in the
      integrated vector control programmes in urban and rural areas.

PMID- 21941568
TI  - Increasing Trend of Resistance to Penicillin, Tetracycline, and Fluoroquinolone
      Resistance in Neisseria gonorrhoeae from Pakistan (1992-2009).
AB  - Emergence and spread of drug resistant Neisseria gonorrhoeae is global concern.
      We evaluated trends of antimicrobial resistance in Neisseria gonorrhoeae over
      years 1992-2009 in Pakistan. Resistance rates were compared between years (2007
      2009) and (1992-2006). Antimicrobial susceptibility testing was performed and
      interpreted according to Clinical Laboratory Standards Institute (CLSI) criteria
      using the disk diffusion methodology against penicillin, ceftriaxone,
      tetracycline and ofloxacin. Additional antibiotics tested in 100 strains isolated
      during 2007-2009, included cefotaxime, cefoxitin, cefuroxime, cefipime,
      ceftazidime, ceftizoxime, cefixime, cefpodoxime, spectinomycin and azithromycin.
      Neisseria gonorrhoeae ATCC 49226 was used as control. Chi-square for trend
      analysis was conducted to assess resistance trend over the study period. During
      study period significant increase in combined resistance to penicillin,
      tetracycline and ofloxacin was observed (P value <0.01). Resistance rates during
      the two study period also increased significantly (P value <0.01). Ceftriaxone
      resistance was not observed. None of the isolates were found to be resistant or
      with intermediate sensitivity to additional antibiotics. Our findings suggest
      that penicillin, ciprofloxacin, tetracycline should not be used in the empirical
      treatment of gonorrhea in Pakistan. Ceftriaxone and cefixime should be the first
      line therapy; however periodic MICs should be determined to identify emergence of
      strains with reduced susceptibility.

PMID- 21941569
TI  - In Vitro Infection of Trypanosoma cruzi Causes Decrease in Glucose Transporter
      Protein-1 (GLUT1) Expression in Explants of Human Placental Villi Cultured under
      Normal and High Glucose Concentrations.
AB  - Trypanosoma cruzi, the etiologic Chagas' disease agent, induces changes in
      protein pattern of the human placenta syncytiotrophoblast. The glucose
      transporter protein-1 (GLUT1) is the primary isoform involved in transplacental
      glucose transport. We carried out in vitro assays to determine if T. cruzi
      infection would induce changes in placental GLUT1 protein expression under normal
      and high concentration of glucose. Using Western blot and immunohistological
      techniques, GLUT1 expression was determined in normal placental villi cultured
      under normal or high concentrations of glucose, with or without in vitro T. cruzi
      infection, for 24 and 48 hours. High glucose media or T. cruzi infection alone
      reduced GLUT1 expression. A yet more accentuated reduction was observed when
      infection and high glucose condition took place together. We inform, for the
      first time, that T. cruzi infection may induce reduction of GLUT1 expression
      under normal and high glucose concentrations, and this effect is synergic to high
      glucose concentrations.

PMID- 21941570
TI  - Anemia in children with down syndrome.
AB  - Background. Iron deficiency anemia impacts on cognitive development. The
      objective of this study was to determine the prevalence of anemia and iron
      deficiency in children with Down syndrome and identify risk factors for anemia.
      Methods. We conducted a prolective cross-sectional study of children attending a
      multidisciplinary Down syndrome medical center. One hundred and forty nine
      children with Down syndrome aged 0-20 years were enrolled in the study.
      Information obtained included a medical history, physical and developmental
      examination, nutritional assessment, and the results of blood tests. Results. Of
      the patients studied, 8.1% were found to have anemia. Among the 38 children who
      had iron studies, 50.0% had iron deficiency. In a multivariate analysis, Arab
      ethnicity and low weight for age were significantly associated with anemia.
      Gender, height, the presence of an eating disorder, and congenital heart disease
      were not risk factors for anemia. Conclusions. Children with Down syndrome are at
      risk for anemia and iron deficiency similar to the general population. Children
      with Down syndrome should be monitored for anemia and iron deficiency so that
      prompt intervention can be initiated.

PMID- 21941571
TI  - Easy and rapid purification of highly active nisin.
AB  - Nisin is an antimicrobial peptide produced and secreted by several L. lactis
      strains and is specifically active against Gram-positive bacteria. In previous
      studies, nisin was purified via cation exchange chromatography at low pH
      employing a single-step elution using 1 M NaCl. Here, we describe an optimized
      purification protocol using a five-step NaCl elution to remove contaminants. The
      obtained nisin is devoid of impurities and shows high bactericidal activity
      against the nisin-sensitive L. lactis strain NZ9000. Purified nisin exhibits an
      IC(50) of ~3 nM, which is a tenfold improvement as compared to nisin obtained via
      the one-step elution procedure.

PMID- 21941572
TI  - Ghrelin o-acyl transferase: bridging ghrelin and energy homeostasis.
AB  - Ghrelin O-acyl transferase (GOAT) is a recently identified enzyme responsible for
      the unique n-acyl modification of ghrelin, a multifunctional metabolic hormone.
      GOAT structure and activity appears to be conserved from fish to man. Since the
      acyl modification is critical for most of the biological actions of ghrelin,
      especially metabolic functions, GOAT emerged as a very important molecule of
      interest. The research on GOAT is on the rise, and several important results
      reiterating its significance have been reported. Notable among these discoveries
      are the identification of GOAT tissue expression patterns, effects on insulin
      secretion, blood glucose levels, feeding, body weight, and metabolism. Several
      attempts have been made to design and test synthetic compounds that can modulate
      endogenous GOAT, which could turn beneficial in favorably regulating whole body
      energy homeostasis. This paper will focus to provide an update on recent advances
      in GOAT research and its broader implications in the regulation of energy
      balance.

PMID- 21941574
TI  - X-ray contrast media mechanisms in the release of mast cell contents:
      understanding these leads to a treatment for allergies.
AB  - A long history of searching for the etiology of X-ray contrast material (CM)
      reactions has led to the understanding that the CM do not produce anti-CM
      antigens. Since CM reactions are anaphylactoid in nature, however, a source for
      mast cell activation was sought. This resulted in the finding that concentrated
      CM could suppress mast cell activation by attachment to the Fc portion of IgE and
      IgG. This is presumed to be a steric hindrance effect. In a study of the effects
      of CM on BP and a study of the effects of CM in sensitized rats, it was concluded
      that less concentrated CM activated mast cells and that this mechanism was best
      explained by bridging of adjacent IgE molecules via attachment to their Fc
      segments. The mast cell release of heparin activating the contact system, as well
      as the release of histamine, is believed to be responsible for CM reactions and
      allergic diatheses.

PMID- 21941573
TI  - Antifungal activities of peptides derived from domain 5 of high-molecular-weight
      kininogen.
AB  - In both immunocompromised and immunocompetent patients, Candida and Malassezia
      are causing or triggering clinical manifestations such as cutaneous infections
      and atopic eczema. The innate immune system provides rapid responses to microbial
      invaders, without requiring prior stimulation, through a sophisticated system of
      antimicrobial peptides (AMPs). High molecular weight kininogen (HMWK) and
      components of the contact system have previously been reported to bind to Candida
      and other pathogens, leading to activation of the contact system. A cutaneous
      Candida infection is characterized by an accumulation of neutrophils, leading to
      an inflammatory response and release of enzymatically active substances. In the
      present study we demonstrate that antifungal peptide fragments are generated
      through proteolytic degradation of HMWK. The recombinant domain 5 (rD5) of HMWK,
      D5-derived peptides, as well as hydrophobically modified D5-derived peptides
      efficiently killed Candida and Malassezia. Furthermore, the antifungal activity
      of modified peptides was studied at physiological conditions. Binding of a D5
      derived peptide, HKH20 (His(479)-His(498)), to the fungal cell membrane was
      visualized by fluorescence microscopy. Our data disclose a novel antifungal
      activity of D5-derived peptides and also show that proteolytic cleavage of HMWK
      results in fragments exerting antifungal activity. Of therapeutic interest is
      that structurally modified peptides show an enhanced antifungal activity.

PMID- 21941575
TI  - Atopic dermatitis and the atopic march: what is new?
AB  - Objective. In this paper the authors review the management of atopic dermatitis
      (AD) and the association between AD and allergic respiratory diseases. Data
      Sources. PubMed databases, researching articles in the last 15 years. Results.
      Studies about atopic march are cross-sectional population studies at different
      ages. They show that the most important predisposing factor for atopy is a
      decrease of the filaggrin's expression. Conclusions. The most modern theories
      seem to show that the most important factor which starts the atopic march is
      represented by an impaired epidermal barrier. It causes an increase in skin
      permeability to allergens that could induce sensitization even in the airways.
      The major predisposing factor is a primary inherited epithelial barrier defect
      resulting from filaggrin gene mutation, but other factors may play a role in this
      complex mechanism. Further studies are needed to focus on AD treatment and
      preventive strategies.

PMID- 21941576
TI  - Eosinophilic Esophagitis in Pediatrics: The Worst of all Possible Allergy Worlds?
AB  - Eosinophilic esophagitis (EoE) is a relatively uncommon allergic disease.
      Presenting with variable gastrointestinal symptoms, the definitive diagnosis is
      made after esophageal visualization and histological confirmation of excessive
      esophageal eosinophils. The scientific discovery of the pathophysiology of EoE
      has been aided by its relationship to other common and well-recognized allergic
      diseases. Similarities and important differences have emerged to distinguish EoE
      as a significant pediatric allergic disease with unique medical care
      requirements.

PMID- 21941577
TI  - Detection of N-glycolyl GM3 ganglioside in neuroectodermal tumors by
      immunohistochemistry: an attractive vaccine target for aggressive pediatric
      cancer.
AB  - The N-glycolylated ganglioside NeuGc-GM3 has been described in solid tumors such
      as breast carcinoma, nonsmall cell lung cancer, and melanoma, but is usually not
      detected in normal human cells. Our aim was to evaluate the presence of NeuGc-GM3
      in pediatric neuroectodermal tumors by immunohistochemistry. Twenty-seven
      archival cases of neuroblastoma and Ewing sarcoma family of tumors (ESFT) were
      analyzed. Formalin-fixed, paraffin-embedded tumor samples were cut into 5 MUm
      sections. The monoclonal antibody 14F7, a mouse IgG1 that specifically recognizes
      NeuGc-GM3, and a peroxidase-labeled polymer conjugated to secondary antibodies
      were used. Presence of NeuGc-GM3 was evident in 23 of 27 cases (85%), with an
      average of about 70% of positive tumors cells. Immunoreactivity was moderate to
      intense in most tumors, showing a diffuse cytoplasmic and membranous staining,
      although cases of ESFT demonstrated a fine granular cytoplasmic pattern. No
      significant differences were observed between neuroblastoma with and without NMYC
      oncogene amplification, suggesting that expression of NeuGc-GM3 is preserved in
      more aggressive cancers. Until now, the expression of N-glycolylated gangliosides
      in pediatric neuroectodermal tumors has not been investigated. The present study
      evidenced the expression of NeuGc-GM3 in a high proportion of neuroectodermal
      tumors, suggesting its potential utility as a specific target of immunotherapy.

PMID- 21941578
TI  - Phenotype and function of CD25-expressing B lymphocytes isolated from human
      umbilical cord blood.
AB  - BACKGROUND: We have shown that approximately 30% of human peripheral blood B
      cells express CD25. B cells expressing CD25 display a mature phenotype belonging
      to the memory B-cell population and have a better proliferative and antigen
      presenting capacity. The aim of the present study was to characterize the CD25
      expressing subset of B cells in human cord blood. MATERIAL AND METHODS:
      Mononuclear cell fraction from human cord blood (n=34) and peripheral adult blood
      (n=22) was sorted into CD20+CD25+ and CD20+CD25- B-cell populations. Phenotype
      and function of these B-cell populations were compared using flow cytometry,
      proliferation, cytokine production, and immunoglobulin secretion. RESULTS: CD25
      expressing B cells are a limited population of cord blood mononuclear cells
      representing 5% of the CD20+ B cells. They are characterised by high expression
      of CD5 in cord blood and CD27 in adult blood. CD25-expressing B cells express a
      functional IL-2 receptor and high levels of CC-chemokine receptors and
      spontaneously produce antibodies of IgG and IgM subclass. CONCLUSIONS: CD25
      expression is a common denominator of a specific immunomodulatory B-cell subset
      ready to proliferate upon IL-2 stimulation, possibly ready to migrate and home
      into the peripheral tissue for further differentiation/action.

PMID- 21941579
TI  - Th1 cytokine-secreting recombinant Mycobacterium bovis bacillus Calmette-Guerin
      and prospective use in immunotherapy of bladder cancer.
AB  - Intravesical instillation of Mycobacterium bovis bacillus Calmette-Guerin (BCG)
      has been used for treating bladder cancer for 3 decades. However, BCG therapy is
      ineffective in approximately 30-40% of cases. Since evidence supports the T
      helper type 1 (Th1) response to be essential in BCG-induced tumor destruction,
      studies have focused on enhancing BCG induction of Th1 immune responses. Although
      BCG in combination with Th1 cytokines (e.g., interferon-alpha) has demonstrated
      improved efficacy, combination therapy requires multiple applications and a large
      quantity of cytokines. On the other hand, genetic manipulation of BCG to secrete
      Th1 cytokines continues to be pursued with considerable interest. To date, a
      number of recombinant BCG (rBCG) strains capable of secreting functional Th1
      cytokines have been developed and demonstrated to be superior to BCG. This paper
      discusses current rBCG research, concerns, and future directions with an
      intention to inspire the development of this very promising immunotherapeutic
      modality for bladder cancer.

PMID- 21941581
TI  - Systemic lupus erythematosus and systemic autoimmune connective tissue disorders
      behind recurrent diastolic heart failure.
AB  - Diastolic heart failure (DHF) remains unexplained in some patients with recurrent
      admissions after full investigation. A study was directed for screening SLE and
      systemic autoimmune connective tissue disorders in recurrent unexplained DHF
      patients admitted at a short-stay and intermediate care unit. It was found that
      systemic autoimmune conditions explained 11% from all of cases. Therapy also
      prevented new readmissions. Autoimmunity should be investigated in DHF.

PMID- 21941580
TI  - RP105-negative B cells in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a multisystem disease characterized by B
      cells producing autoantibodies against nuclear proteins and DNA, especially anti
      double-strand DNA (dsDNA) antibodies. RP105 (CD180), the toll-like receptor- (TLR
      ) associated molecule, is expressed on normal B cells. However, RP105-negative B
      cells increase in peripheral blood from patients with active SLE. RP105 may
      regulate B-cell activation, and RP105-negative B cells produce autoantibodies and
      take part in pathophysiology of SLE. It is possible that targeting RP105-negative
      B cells is one of the treatments of SLE. In this paper, we discuss the RP105
      biology and clinical significance in SLE.

PMID- 21941582
TI  - Genetic risk factors of systemic lupus erythematosus in the Malaysian population:
      a minireview.
AB  - SLE is an autoimmune disease that is not uncommon in Malaysia. In contrast to
      Malays and Indians, the Chinese seem to be most affected. SLE is characterized by
      deficiency of body's immune response that leads to production of autoantibodies
      and failure of immune complex clearance. This minireview attempts to summarize
      the association of several candidate genes with risk for SLE in the Malaysian
      population and discuss the genetic heterogeneity that exists locally in Asians
      and in comparison with SLE in Caucasians. Several groups of researchers have been
      actively investigating genes that are associated with SLE susceptibility in the
      Malaysian population by screening possible reported candidate genes across the
      SLE patients and healthy controls. These candidate genes include MHC genes and
      genes encoding complement components, TNF, FcgammaR, T-cell receptors, and
      interleukins. However, most of the polymorphisms investigated in these genes did
      not show significant associations with susceptibility to SLE in the Malaysian
      scenario, except for those occurring in MHC genes and genes coding for TNF-alpha,
      IL-1beta, IL-1RN, and IL-6.

PMID- 21941583
TI  - Cardiovascular risk in systemic autoimmune diseases: epigenetic mechanisms of
      immune regulatory functions.
AB  - Autoimmune diseases (AIDs) have been associated with accelerated atherosclerosis
      (AT) leading to increased cardio- and cerebrovascular disease risk. Traditional
      risk factors, as well as systemic inflammation mediators, including cytokines,
      chemokines, proteases, autoantibodies, adhesion receptors, and others, have been
      implicated in the development of these vascular pathologies. Yet, the
      characteristics of vasculopathies may significantly differ depending on the
      underlying disease. In recent years, many new genes and signalling pathways
      involved in autoimmunity with often overlapping patterns between different
      disease entities have been further detected. Epigenetics, the control of gene
      packaging and expression independent of alterations in the DNA sequence, is
      providing new directions linking genetics and environmental factors. Epigenetic
      regulatory mechanisms comprise DNA methylation, histone modifications, and
      microRNA activity, all of which act upon gene and protein expression levels.
      Recent findings have contributed to our understanding of how epigenetic
      modifications could influence AID development, not only showing differences
      between AID patients and healthy controls, but also showing how one disease
      differs from another and even how the expression of key proteins involved in the
      development of each disease is regulated.

PMID- 21941584
TI  - Examining brain-cognition effects of ginkgo biloba extract: brain activation in
      the left temporal and left prefrontal cortex in an object working memory task.
AB  - Ginkgo Biloba extract (GBE) is increasingly used to alleviate symptoms of age
      related cognitive impairment, with preclinical evidence pointing to a pro
      cholinergic effect. While a number of behavioral studies have reported
      improvements to working memory (WM) associated with GBE, electrophysiological
      studies of GBE have typically been limited to recordings during a resting state.
      The current study investigated the chronic effects of GBE on steady state
      visually evoked potential (SSVEP) topography in nineteen healthy middle-aged (50
      61 year old) male participants whilst completing an object WM task. A randomized
      double-blind crossover design was employed in which participants were allocated
      to receive 14 days GBE and 14 days placebo in random order. For both groups,
      SSVEP was recorded from 64 scalp electrode sites during the completion of an
      object WM task both pre- and 14 days post-treatment. GBE was found to improve
      behavioural performance on the WM task. GBE was also found to increase the SSVEP
      amplitude at occipital and frontal sites and increase SSVEP latency at left
      temporal and left frontal sites during the hold component of the WM task. These
      SSVEP changes associated with GBE may represent more efficient processing during
      WM task completion.

PMID- 21941585
TI  - The largest Bio-Silica Structure on Earth: The Giant Basal Spicule from the Deep
      Sea Glass Sponge Monorhaphis chuni.
AB  - The depth of the ocean is plentifully populated with a highly diverse fauna and
      flora, from where the Challenger expedition (1873-1876) treasured up a rich
      collection of vitreous sponges [Hexactinellida]. They have been described by
      Schulze and represent the phylogenetically oldest class of siliceous sponges
      [phylum Porifera]; they are eye-catching because of their distinct body plan,
      which relies on a filigree skeleton. It is constructed by an array of
      morphologically determined elements, the spicules. Later, during the German Deep
      Sea Expedition "Valdivia" (1898-1899), Schulze could describe the largest
      siliceous hexactinellid sponge on Earth, the up to 3 m high Monorhaphis chuni,
      which develops the equally largest bio-silica structures, the giant basal
      spicules (3 m * 10 mm). With such spicules as a model, basic knowledge on the
      morphology, formation, and development of the skeletal elements could be
      elaborated. Spicules are formed by a proteinaceous scaffold which mediates the
      formation of siliceous lamellae in which the proteins are encased. Up to eight
      hundred 5 to 10 MUm thick lamellae can be concentrically arranged around an axial
      canal. The silica matrix is composed of almost pure silicon and oxygen, providing
      it with unusual optophysical properties that are superior to those of man-made
      waveguides. Experiments indicated that the spicules function in vivo as a
      nonocular photoreception system. In addition, the spicules have exceptional
      mechanical properties, combining mechanical stability with strength and
      stiffness. Like demosponges the hexactinellids synthesize their silica
      enzymatically, via the enzyme silicatein. All these basic insights will surely
      contribute also to a further applied utilization and exploration of bio-silica in
      material/medical science.

PMID- 21941586
TI  - Peripheral Nerve Regeneration Following Crush Injury to Rat Peroneal Nerve by
      Aqueous Extract of Medicinal Mushroom Hericium erinaceus (Bull.: Fr) Pers.
      (Aphyllophoromycetideae).
AB  - Nerve crush injury is a well-established axonotmetic model in experimental
      regeneration studies to investigate the impact of various pharmacological
      treatments. Hericium erinaceus is a temperate mushroom but is now being
      cultivated in tropical Malaysia. In this study, we investigated the activity of
      aqueous extract of H. erinaceus fresh fruiting bodies in promoting functional
      recovery following an axonotmetic peroneal nerve injury in adult female Sprague
      Dawley rats by daily oral administration. The aim was to investigate the possible
      use of this mushroom in the treatment of injured nerve. Functional recovery was
      assessed in behavioral experiment by walking track analysis. Peroneal functional
      index (PFI) was determined before surgery and after surgery as rats showed signs
      of recovery. Histological examinations were performed on peroneal nerve by
      immunofluorescence staining and neuromuscular junction by combined silver
      cholinesterase stain. Analysis of PFI indicated that return of hind limb function
      occurred earlier in rats of aqueous extract or mecobalamin (positive control)
      group compared to negative control group. Regeneration of axons and reinnervation
      of motor endplates in extensor digitorum longus muscle in rats of aqueous extract
      or mecobalamin group developed better than in negative control group. These data
      suggest that daily oral administration of aqueous extract of H. erinaceus fresh
      fruiting bodies could promote the regeneration of injured rat peroneal nerve in
      the early stage of recovery.

PMID- 21941587
TI  - Novel diagnostic model for the deficient and excess pulse qualities.
AB  - The deficient and excess pulse qualities (DEPs) are the two representatives of
      the deficiency and excess syndromes, respectively. Despite its importance in the
      objectification of pulse diagnosis, a reliable classification model for the DEPs
      has not been reported to date. In this work, we propose a classification method
      for the DEPs based on a clinical study. First, through factor analysis and
      Fisher's discriminant analysis, we show that all the pulse amplitudes obtained at
      various applied pressures at Chon, Gwan, and Cheok contribute on equal orders of
      magnitude in the determination of the DEPs. Then, we discuss that the pulse
      pressure or the average pulse amplitude is appropriate for describing the
      collective behaviors of the pulse amplitudes and a simple and reliable
      classification can be constructed from either quantity. Finally, we propose an
      enhanced classification model that combines the two complementary variables
      sequentially.

PMID- 21941588
TI  - A therapeutic approach for wound healing by using essential oils of cupressus and
      juniperus species growing in Turkey.
AB  - Juniperus and Cupressus genera are mainly used as diuretic, stimulant, and
      antiseptic, for common cold and wound healing in Turkish folk medicine. In the
      present study, essential oils obtained from cones of Cupressus and berries of
      Juniperus were evaluated for their wound healing and anti-inflammatory effects.
      In vivo wound healing activity was evaluated by linear incision and circular
      excision experimental wound models, assessment of hydroxyproline content, and
      subsequently histopathological analysis. The healing potential was comparatively
      assessed with a reference ointment Madecassol. Additionally acetic-acid-induced
      capillary permeability test was used for the oils' anti-inflammatory activity.
      The essential oils of J. oxycedrus subsp. oxycedrus and J. phoenicea demonstrated
      the highest activities, while the rest of the species did not show any
      significant wound healing effect. The experimental study revealed that J.
      oxycedrus subsp. oxycedrus and J. phoenicea display remarkable wound healing and
      anti-inflammatory activities, which support the folkloric use of the plants.

PMID- 21941589
TI  - Immunomodulatory Effect of Rhaphidophora korthalsii on Natural Killer Cell
      Cytotoxicity.
AB  - The in vivo immunomodulatory effect of ethanolic extracts from leaves of
      Rhaphidophora korthalsii was determined via immune cell proliferation, T/NK cell
      phenotyping, and splenocyte cytotoxicity of BALB/c mice after 5 consecutive days
      of i.p. administration at various concentrations. Splenocyte proliferation index,
      cytotoxicity, peripheral blood T/NK cell population, and plasma cytokine (IL-2
      and IFN-gamma) in mice were assessed on day 5 and day 15. High concentration of
      extract (350 MUg/mice/day for 5 consecutive days) was able to stimulate immune
      cell proliferation, peripheral blood NK cell population, IL-2, and IFN- gamma
      cytokines, as well as splenocyte cytotoxicity against Yac-1 cell line. Unlike rIL
      2 which degraded rapidly, the stimulatory effect from the extract managed to last
      until day 15. These results suggested the potential of this extract as an
      alternative immunostimulator, and they encourage further study on guided
      fractionation and purification to identify the active ingredients that contribute
      to this in vitro and in vivo immunomodulatory activity.

PMID- 21941590
TI  - Gelam (Melaleuca spp.) Honey-Based Hydrogel as Burn Wound Dressing.
AB  - A novel cross-linked honey hydrogel dressing was developed by incorporating
      Malaysian honey into hydrogel dressing formulation, cross-linked and sterilized
      using electron beam irradiation (25 kGy). In this study, the physical properties
      of the prepared honey hydrogel and its wound healing efficacy on deep partial
      thickness burn wounds in rats were assessed. Skin samples were taken at 7, 14,
      21, and 28 days after burn for histopathological and molecular evaluations.
      Application of honey hydrogel dressings significantly enhanced (P < 0.05) wound
      closure and accelerated the rate of re-epithelialization as compared to control
      hydrogel and OpSite film dressing. A significant decrease in inflammatory
      response was observed in honey hydrogel treated wounds as early as 7 days after
      burn (P < 0.05). Semiquantitative analysis using RT-PCR revealed that treatment
      with honey hydrogel significantly (P < 0.05) suppressed the expression of
      proinflammatory cytokines (IL-1alpha, IL-1beta, and IL-6). The present study
      substantiates the potential efficacy of honey hydrogel dressings in accelerating
      burn wound healing.

PMID- 21941591
TI  - Ginsenoside-Rg1 Protects the Liver against Exhaustive Exercise-Induced Oxidative
      Stress in Rats.
AB  - Despite regular exercise benefits, acute exhaustive exercise elicits oxidative
      damage in liver. The present study determined the hepatoprotective properties of
      ginsenoside-Rg1 against exhaustive exercise-induced oxidative stress in rats.
      Forty rats were assigned into vehicle and ginsenoside-Rg1 groups (0.1 mg/kg
      bodyweight). After 10-week treatment, ten rats from each group performed
      exhaustive swimming. Estimated oxidative damage markers, including thiobarbituric
      acid reactive substance (TBARS) (67%) and protein carbonyls (56%), were
      significantly (P < 0.01) elevated after exhaustive exercise but alleviated in
      ginsenoside-Rg1 pretreated rats. Furthermore, exhaustive exercise drastically
      decreased glutathione (GSH) content (~79%) with concurrent decreased superoxide
      dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities.
      However, these changes were attenuated in Rg1 group. Additionally, increased
      xanthine oxidase (XO) activity and nitric oxide (NO) levels after exercise were
      also inhibited by Rg1 pretreatment. For the first time, our findings provide
      strong evidence that ginsenoside-Rg1 can protect the liver against exhaustive
      exercise-induced oxidative damage.

PMID- 21941592
TI  - Sasang constitutional medicine and traditional chinese medicine: a comparative
      overview.
AB  - Sasang constitutional medicine (SCM) is a holistic typological constitution
      medicine which balances psychological, social, and physical aspects of an
      individual to achieve wellness and increase longevity. SCM has the qualities of
      preventative medicine, as it emphasizes daily health management based on
      constitutionally differentiated regimens and self-cultivation of the mind and
      body. This review's goal is to establish a fundamental understanding of SCM and
      to provide a foundation for further study. It compares the similarities and
      differences of philosophical origins, perspectives on the mind (heart),
      typological systems, pathology, and therapeutics between SCM and traditional
      Chinese medicine (TCM). TCM is based on the Taoist view of the universe and
      humanity. The health and longevity of an individual depends on a harmonious
      relationship with the universe. On the other hand, SCM is based on the Confucian
      view of the universe and humanity. SCM focuses on the influence of human affairs
      on the psyche, physiology, and pathology.

PMID- 21941593
TI  - Efficient CT metal artifact reduction based on fractional-order curvature
      diffusion.
AB  - We propose a novel metal artifact reduction method based on a fractional-order
      curvature driven diffusion model for X-ray computed tomography. Our method treats
      projection data with metal regions as a damaged image and uses the fractional
      order curvature-driven diffusion model to recover the lost information caused by
      the metal region. The numerical scheme for our method is also analyzed. We use
      the peak signal-to-noise ratio as a reference measure. The simulation results
      demonstrate that our method achieves better performance than existing projection
      interpolation methods, including linear interpolation and total variation.

PMID- 21941594
TI  - Endoscopic mucosal resection: who and how?

PMID- 21941596
TI  - Illuminating the deleterious effects of light at night.
AB  - Technological advances, while providing many benefits, often create circumstances
      that differ from the conditions in which we evolved. With the wide-spread
      adoption of electrical lighting during the 20(th) century, humans became exposed
      to bright and unnatural light at night for the first time in their evolutionary
      history. Electrical lighting has led to the wide-scale practice of 24-hour shift
      work and has meant that what were once just "daytime" activities now run
      throughout the night; in many ways Western society now functions on a 24-hour
      schedule. Recent research suggests that this gain in freedom to function
      throughout the night may also come with significant repercussions. Disruption of
      our naturally evolved light and dark cycles can result in a wide range of
      physiological and behavioral changes with potentially serious medical
      implications. In this article we will discuss several mechanisms through which
      light at night may exert its effects on cancer, mood, and obesity, as well as
      potential ways to ameliorate the impact of light at night.

PMID- 21941595
TI  - Advancements in adeno-associated viral gene therapy approaches: exploring a new
      horizon.
AB  - Gene therapy is a promising new therapeutic strategy that has been explored in a
      wide variety of diseases, ranging from cancer to hemophilia, and ocular disorders
      to autoimmune diseases, among others. Proof of concept of gene transfer
      approaches has been shown in over 100 studies of animal models of disease,
      although only a few are under development for clinical application. The US Food
      and Drug Administration and the European Medicines Agency have not approved any
      viral human gene therapy products for sale so far, but the amount of gene-related
      research and development occurring in the United States and Europe continues to
      grow at a fast rate. This review summarizes the current status of developments in
      the field of viral gene therapy using adeno-associated virus as a vector, with a
      special focus on arthritis. For rheumatoid arthritis, and to a lesser extent for
      other immune-related inflammatory disorders, several cell and gene transfer
      approaches have been investigated at the preclinical level and a few have been
      implemented in clinical trials. Finally, both the potential and the hurdles that
      are faced during development of a viral gene therapy through to its clinical
      application are discussed.

PMID- 21941597
TI  - Amyotrophic lateral sclerosis: new genes, new models, and new mechanisms.
AB  - Research aimed at understanding amyotrophic lateral sclerosis (ALS) has seen
      exceptional growth in the past few years. New genes, new models, and new
      mechanisms have not only improved our understanding, but also contributed to the
      increasing complexity of ALS pathogenesis. The focus of this piece is to
      highlight some of the more notable developments in the field and to encourage a
      re-appreciation for the superoxide dismutase 1 (SOD1) mouse models.

PMID- 21941598
TI  - Conformational selection or induced fit? 50 years of debate resolved.
AB  - Exactly 50 years ago, biochemists raised the question of the mechanism of the
      conformational change that mediates "allosteric" interactions between regulatory
      sites and biologically active sites in regulatory/receptor proteins. Do the
      different conformations involved already exist spontaneously in the absence of
      the regulatory ligands (Monod-Wyman-Changeux), such that the complementary
      protein conformation would be selected to mediate signal transduction, or do
      particular ligands induce the receptor to adopt the conformation best suited to
      them (Koshland-Nemethy-Filmer-induced fit)? This is not just a central question
      for biophysics, it also has enormous importance for drug design. Recent advances
      in techniques have allowed detailed experimental and theoretical comparisons with
      the formal models of both scenarios. Also, it has been shown that mutated
      receptors can adopt constitutively active confirmations in the absence of ligand.
      There have also been demonstrations that the atomic resolution structures of the
      same protein are essentially the same whether ligand is bound or not. These and
      other advances in past decades have produced a situation where the vast majority
      of the data using different categories of regulatory proteins (including
      regulatory enzymes, ligand-gated ion channels, G protein-coupled receptors, and
      nuclear receptors) support the conformational selection scheme of signal
      transduction.

PMID- 21941600
TI  - Multiple organ failure secondary to multiple organism bacteraemia associated with
      intestinal ischaemia in a patient with a phaeochromocytoma.
AB  - Phaeochromocytomas are rare catecholamine secreting tumours that usually present
      as paroxysms of hypertension associated with headache, palpitations and sweating.
      We report the case of a 50-year-old man with a phaeochromocytoma who presented
      with sudden onset of hypertension, syncope, and fever who later developed a
      multiple-organ failure secondary to a multiple organism bacteraemias due to
      transient episodes of intestinal ischaemia. After receiving full intensive care
      support, antibiotics and tumour removal, the patient made a complete recovery and
      he is at present doing well. This case illustrates that high concentrations of
      catecholamine secreted by a phaeochromocytoma might cause multiple organ failure
      syndrome secondary to multiple organism bacteraemias due to transient episodes of
      intestinal ischaemia.

PMID- 21941599
TI  - Taste isn't just for taste buds anymore.
AB  - Taste is a discriminative sense involving specialized receptor cells of the oral
      cavity (taste buds) and at least two distinct families of G protein-coupled
      receptor molecules that detect nutritionally important substances or potential
      toxins. Yet the receptor mechanisms that drive taste also are utilized by
      numerous systems throughout the body. How and why these so-called taste receptors
      are used to regulate digestion and respiration is now a matter of intense study.
      In this article we provide a historical perspective and an overview of these
      systems, leading to speculations on directions for further research.

PMID- 21941601
TI  - Leiomyoma of the temporal artery.
AB  - A 25-year-old man had a right sided cyst-like swelling removed from his forehead.
      Histology revealed a well circumscribed spindle cell lesion with myxomatous
      changes. Immunohistochemical staining with muscle markers (smooth muscle actin,
      muscle specific actin) was positive. The histological features along with the
      immunohistochemical staining profile are of a leiomyoma with myxoid change
      arising in the temporal artery. Leiomyomata arising from vessels are extremely
      rare and to our knowledge this is the first case arising from the temporal
      artery.

PMID- 21941602
TI  - In vitro anticancer activity of Anemopsis californica.
AB  - Three different extract conditions (aqueous, EtOH and EtOAc) of four different
      parts (bracts, leaves, roots and stems) of the plant Anemopsis californica (A.
      californica) were evaluated for their effect on the growth and migration of human
      colon cancer cells, HCT-8, and the breast cancer cell lines Hs 578T and MCF-7/AZ.
      Our aim was to identify potential anticancer activity in crude A. californica
      extracts, given that this plant is used by Native Americans to treat a variety of
      diseases, including cancer. Our results demonstrated that for each of the cell
      lines tested, the majority of ethyl acetate extracts of all the plant parts are
      more toxic than the aqueous and ethanol extracts. Furthermore, significant growth
      inhibitory activity against the three cell lines was found for the ethyl acetate
      extract of the roots, while the aqueous extract of the roots influenced the
      migratory capacity of the three cell lines. This study provides evidence for the
      anticancer properties of A. californica when extracted in water and ethyl
      acetate, and supports the importance for further purification of the crude
      extracts and isolation of potential new anticancer compounds through bio-guided
      fractionation.

PMID- 21941603
TI  - Racial/Ethnic differences in quality of life for people living with arthritis who
      see a primary care physician.
AB  - OBJECTIVE: Previous research suggests that insufficient access to health care may
      contribute to health disparities in arthritis-related outcomes. The purpose of
      this article is to document whether racial disparities in health status, health
      related quality of life (HRQOL), and activity limitations exist for individuals
      living with arthritis who have access to a primary care physician. METHODS: Cross
      sectional survey data were collected in 2005 and 2008 from individuals seeking
      care at 11 family practice clinics in North Carolina. Participants self-reported
      their arthritis status, health status, physical and mental HRQOL, and activity
      limitations. Analysis of variance was used to determine whether there were
      differences in demographic and clinical characteristics of White (n= 405), Black
      (n = 244), and Latino (n = 100) participants who self-reported arthritis. Linear
      regressions determined whether race/ethnicity was significantly associated with
      HRQOL and activity limitations; whereas, logistic regression determined whether
      the odds of poor health were higher for Black and Latino participants,
      controlling for age, gender, body mass index, marital status, and number of
      comorbid conditions. RESULTS: Over 50% of participants reported fair/poor health
      status and more than 8 days of poor physical and mental health and 6 days of
      activity limitations during the past month. Latino participants were more likely
      to report fair/poor health status and fewer activity limitations than Whites or
      Blacks, whereas Black participants reported fewer days of poor mental health.
      CONCLUSION: Despite access to a primary care physician, racial/ethnic disparities
      exist. Future research should explore the underlying reasons for the persistence
      of these disparities.

PMID- 21941604
TI  - Targeting HDACs: a promising therapy for Alzheimer's disease.
AB  - Epigenetic modifications like DNA methylation and histone acetylation play an
      important role in a wide range of brain disorders. Histone deacetylases (HDACs)
      regulate the homeostasis of histone acetylation. Histone deacetylase inhibitors,
      which initially were used as anticancer drugs, are recently suggested to act as
      neuroprotectors by enhancing synaptic plasticity and learning and memory in a
      wide range of neurodegenerative and psychiatric disorders, such as Alzheimer's
      disease (AD) and Parkinson's disease (PD). To reveal the physiological roles of
      HDACs may provide us with a new perspective to understand the mechanism of AD and
      to develop selective HDAC inhibitors. This paper focuses on the recent research
      progresses of HDAC proteins and their inhibitors on the roles of the treatment
      for AD.

PMID- 21941605
TI  - Ameliorative effects of herbal combinations in hyperlipidemia.
AB  - The roots of Glycyrrhiza glabra, Withania somnifera, Asparagus racemosus, and
      Chlorophytum borivilianum and seeds of Sesamum indicum are ayurvedic medicinal
      plants used in India to treat several ailments. Our previous studies indicated
      that these plants possess hypolipidemic and antioxidant potential. The present
      study was aimed at investigating the composite effects of these plants on
      hypercholesterolemic rats. Three different combinations (5 gm%, given for four
      weeks) used in this study effectively reduced plasma and hepatic lipid profiles
      and increased fecal excretion of cholesterol, neutral sterol, and bile acid along
      with increasing the hepatic HMG-CoA reductase activity and bile acid content in
      hypercholesterolemic rats. Further, all three combinations also improved the
      hepatic antioxidant status (catalase, SOD, and ascorbic acid levels) and plasma
      total antioxidant capacity with reduced hepatic lipid peroxidation. Overall,
      combination I had the maximum effect on hypercholesterolemic rats followed by
      combinations II and III due to varying concentrations of the different classes of
      phytocomponents.

PMID- 21941606
TI  - Evaluation of chromosomal instability in diabetic rats treated with naringin.
AB  - We used the bone marrow DNA strand breaks, micronucleus formations, spermatocyte
      chromosomal aberrations, and sperm characteristic assays to investigate the
      chromosomal instability in somatic and germinal cells of diabetic rats treated
      with multiple doses of naringin. The obtained results revealed that naringin was
      neither cytotoxic nor genotoxic for the rats at all tested doses. Moreover,
      naringin significantly reduced the diabetes-induced chromosomal instability in
      somatic and germinal cells in a dose-dependent manner. In addition, diabetes
      induced marked biochemical alterations characteristic of oxidative stress
      including enhanced lipid peroxidation, accumulation of oxidized glutathione,
      reduction in reduced glutathione, and accumulation of intracellular reactive
      oxygen species. Treatment with naringin ameliorated these biochemical markers
      dose-dependently. In conclusion, naringin confers an appealing protective effect
      against diabetes-induced chromosomal instability towards rat somatic and germinal
      cells which might be explained partially via diminishing the de novo free radical
      generation induced by hyperglycemia. Thus, naringin might be a good candidate to
      reduce genotoxic risk associated with hyperglycemia and may provide decreases in
      the development of secondary malignancy and abnormal reproductive outcomes risks,
      which seems especially important for diabetic patients.

PMID- 21941608
TI  - Gene expression profile in the diaphragm following contractile inactivity during
      thoracic surgery.
AB  - Introduction. Recent work revealed the development of marked muscle fiber
      weakness in the diaphragm, but not in the non-respiratory latissimus dorsi,
      during thoracic surgery. To disentangle the molecular processes that underlie the
      development of diaphragm muscle fiber weakness during thoracic surgery, we
      studied changes in the gene expression profile. Methods. Serial biopsies from the
      diaphragm and the latissimus dorsi muscle were obtained from four patients during
      thoracotomy for resection of a tumor in the right lung. Biopsies were taken as
      soon as the diaphragm had been exposed (t0) and again after two hours (t2). Gobal
      differences in gene expression in diaphragm biopsies were assessed by microarray
      analysis. Results. 346 differentially expressed gene transcripts were found in
      the diaphragm at t2 vs. t0. Pathway analysis revealed that genes associated with
      inflammation (83 genes; p<0.0001) and cell death (118 genes, p<0.0001) pathways
      were significantly overexpressed at t2. Of the 346 differentially expressed genes
      in the diaphragm at t2, 258 were also differential in the latissimus dorsi
      muscle, with the direction of change being identical for all differentially
      expressed genes. In addition, latissimus dorsi showed exclusive upregula-ton of
      negative regulators of cell death. Conclusions. Two hours of thoracic surgery
      result in rapid and profound changes in expression of inflammatory response and
      apoptotic genes in the diaphragm. The apoptotic response was stronger in the
      diaphragm than in the latissiums dorsi. These findings suggest that the
      development of selective diaphragm muscle fiber weakness in these patients might
      be related to an exaggerated apoptotic response.

PMID- 21941607
TI  - Internalization of Staphylococcus aureus in lymphocytes induces oxidative stress
      and DNA fragmentation: possible ameliorative role of nanoconjugated vancomycin.
AB  - Staphylococcus aureus is the most frequently isolated pathogen causing
      bloodstream infections, skin and soft tissue infections and pneumonia. Lymphocyte
      is an important immune cell. The aim of the present paper was to test the
      ameliorative role of nanoconjugated vancomycin against Vancomycin-sensitive
      Staphylococcus aureus (VSSA) and vancomycin-resistant Staphylococcus aureus
      (VRSA) infection-induced oxidative stress in lymphocytes. VSSA and VRSA
      infections were developed in Swiss mice by intraperitoneal injection of 5 * 10(6)
      CFU/mL bacterial solutions. Nanoconjugated vancomycin was adminstrated to VSSA-
      and VRSA-infected mice at its effective dose for 10 days. Vancomycin was
      adminstrated to VSSA- and VRSA-infected mice at a similar dose, respectively, for
      10 days. Vancomycin and nanoconjugated vancomycin were adminstrated to normal
      mice at their effective doses for 10 days. The result of this study reveals that
      in vivo VSSA and VRSA infection significantly increases the level of lipid
      peroxidation, protein oxidation, oxidized glutathione level, nitrite generation,
      nitrite release, and DNA damage and decreases the level of reduced glutathione,
      antioxidant enzyme status, and glutathione-dependent enzymes as compared to
      control group, which were increased or decreased significantly near to normal in
      nanoconjugated vancomycin-treated group. These findings suggest the potential use
      and beneficial role of nanoconjugated vancomycin against VSSA and VRSA infection
      induced oxidative stress in lymphocytes.

PMID- 21941609
TI  - Histopathologic evaluation of lung and extrapulmonary tissues show sex
      differences in Klebsiella pneumoniae - infected mice under different exposure
      conditions.
AB  - It has been shown that female mice with pneumonia have a survival advantage over
      males, but this is reversed if ozone exposure precedes infection. The purpose of
      this study was to investigate factors that underlie these observations, by
      studying histopathologic changes in lung and extrapulmonary (spleen and liver)
      tissues after ozone or filtered air (FA) exposure followed by pulmonary bacterial
      infection. Male and female wild type C57BL/6J mice were exposed to ozone or FA,
      then anesthetized and infected intratracheally with Klebsiella pneumoniae
      bacteria. Tissues (lung, spleen, and liver) were subjected to histopathologic
      analysis at 48 h post-infection. We found that after infection, 1) the severity
      of inflammation was higher, the affected area of the lung was larger, and spleen
      red pulp myelopoiesis was lower in ozone-exposed mice compared to FA-exposed
      animals in both sexes; 2) more pronounced extrapulmonary lesions (in liver and
      spleen) were observed in FA-exposed males compared to FA-exposed females; and 3)
      excessive lung inflammatory response was detected in ozone-exposed females
      compared to ozone-exposed males. We concluded that different risk factors
      contribute to the differential outcome of pneumonia between sexes in the presence
      or absence of ozone-induced oxidative stress. In specific, the excessive lung
      inflammation and higher risk for extrapulmonary lesions in ozone-exposed infected
      females and in FA-exposed infected males appear to play, respectively, a dominant
      role in the previously observed respective survival outcomes.

PMID- 21941611
TI  - Cutaneous vasomotor reactions in response to controlled heat applied on various
      body regions of healthy humans: evaluation of time course and application
      parameters.
AB  - Skin permeability and local blood perfusion are important factors for transdermal
      drug delivery. Application of heat is expected to enhance microcirculation and
      local perfusion and/or blood vessel permeability, thus facilitating drug transfer
      to the systemic circulation. In addition, heating prior to or during topical
      application of a drug may facilitate skin penetration, increase kinetic energy,
      and facilitate drug absorption. The aim of the present study was to investigate
      skin vasomotor responses to mild heat generated by a controlled heat device on
      several body regions of healthy male and female subjects. Skin vasomotor
      responses in different body regions were recorded following different heat
      application paradigms (38, 41 and 43  degrees C, each for 15, 30, 60 sec). Test
      regions were forehead, forearm, dorsal hand, dorsal foot, and abdomen. Prior to
      and following the application of heat, local blood perfusion and skin temperature
      were measured by means of laser Doppler imaging (LDI) and thermography,
      respectively. It was found that a short-lasting heat application (43  degrees C
      for 60 sec) causes significant cutaneous hyperaemia (up to 2 folds increase in
      skin perfusion, and 5  degrees C increase in skin temperature) existing for up to
      15 minutes. The site of application and sex did not influence the responses. The
      method was well tolerated without causing any pain or discomfort. These data
      suggest that controlled heat application is a simple, non-invasive method to
      significantly enhance local perfusion which may improve transcutaneous drug
      delivery.

PMID- 21941610
TI  - Hypoxia regulates the natriuretic peptide system.
AB  - Numerous clinical studies have addressed the role of the natriuretic peptide
      system either as a diagnostic tool or as a guide to treatment in many cardiac
      diseases. The concept behind these studies has been that intravascular overload
      produces cardiac wall stress that alone stimulates the synthesis and release of
      natriuretic peptides the result of which is diuresis, natriuresis, and
      vasodilatation. However, almost thirty years after the discovery of the
      natriuretic peptides the measurement of these peptides, especially the BNP, has
      not met all the expectations of a simple and useful diagnostic tool in clinical
      cardiology, possibly due to confounding factors confusing the interpretation of
      the wall stress effect. In the same way as in pressure studies, it has been shown
      that hypoxia is a direct and sufficient stimulus for the synthesis and release of
      ANP and BNP. Additionally, hypoxia-response elements have been characterized from
      the promoter sequence of both the ANP and the BNP genes. Furthermore, a
      physiological rhythm (eupnea-apnea), causing changes in blood oxygen tension,
      regulates the plasma levels of ANP in sleeping seal pups which are spontaneously
      able to hold back their breathing. We suggest, on the basis of the extensive
      published literature, that the stimulus for the synthesis and release of
      natriuretic peptides is the oxygen gradient which always occurs in all human
      tissues in physiological conditions. The plasma volume contraction caused by
      natriuretic peptides (natriuresis, diuresis, and plasma shift) leads to
      hemoconcentration and ultimately to the increased oxygen-carrying capacity of
      unit volume of blood.

PMID- 21941612
TI  - Cystathionine beta synthase gene dose dependent vascular remodeling in murine
      model of hyperhomocysteinemia.
AB  - Although children born with severe homocystinurea (i.e. cystathionine beta
      synthase homozygote knockout, CBS-/-) develop deleterious vascular complications
      with structural malformation and do not live past teenage, the heterozygote (CBS
      /+) lives with apparently normal phenotype. Interestingly, this differential role
      of CBS expression in vascular remodeling is unclear. Peroxisome proliferator
      activated receptor gamma (PPARgamma) is nuclear transcription factor that
      mitigates vascular complications. The hypothesis was that homocysteine (Hcy)
      decreased thioredoxin (Trx), peroxiredoxin (Prx), increased NADPH oxidase (NOX1),
      mitochondrial nitric oxide synthase (mtNOS) activity and reactive oxygen species
      (ROS) in mitochondria in a CBS gene dose-dependent manner. ROS transduced matrix
      metalloproteinase (MMP) activation causing thickening (fibrosis) of the basement
      membrane, rendering ineffective endothelial nitric oxide synthase (eNOS) and
      promoted endothelial-smooth muscle disconnection/uncoupling by antagonizing
      PPARgamma. Wild type (WT-CBS+/+), CBS-/+ and CBS -/- mice were treated with or
      without ciglitazone (CZ, a PPARgamma agonist) in food at birth. Aortic nuclear
      PPARgamma expression was measured by EMSA. Aortic mtNOS activity and ROS
      production was measured using NO- and H(2)O(2)-electrodes, respectively. Aorta
      was analyzed for Trx, Prx, by Western blot, and PCR. MMP activity was by in situ
      zymography. Aortic function was measured in tissue myobath. The results suggested
      90% morbidity in CBS-/- allele at 12 wks. However, treatment with the PPARgamma
      agonist, CZ significantly reduced the morbidity to 20%. In addition, CZ restored
      the PPARgamma activity in CBS-/+ and -/- mice to normal levels. The oxidative
      stress was alleviated by CZ treatment. In situ labeling with mito-tracker
      suggests co-localization of ROS with mitochondrial mitophagy. The mtNOS activity
      was increased in HHcy compared to WT. The data support the notion that Hcy
      decreases redoxins, increases mtNOS activity and ROS/oxidase in mitochondrial
      mitophagy in a gene dose-dependent manner of CBS. ROS transduces MMP activation,
      rendering ineffective eNOS and promotes endothelial-smooth muscle
      disconnection/uncoupling by antagonizing PPARgamma. We suggest that the children
      born with severe ho-mocystineurea may do better if treated with PPARgamma
      agonist.

PMID- 21941614
TI  - Effect of local controlled heat on transdermal delivery of nicotine.
AB  - Skin permeability and local blood perfusion are important factors for transdermal
      drug delivery. Application of heat is expected to enhance microcirculation and
      local perfusion and/or blood vessel permeability, thus facilitating drug transfer
      to the systemic circulation. In addition, heating prior to or during topical
      application of a drug may facilitate skin penetration, increase kinetic energy,
      and facilitate drug absorption. The aim of the present study was to investigate
      whether application of controlled local heat would enhance transdermal delivery
      from the nicotine patch mounted on the upper arm of ten healthy non-smoking male
      Caucasian subjects. Local skin perfusion was monitored using Laser Doppler
      Imaging (LDI) at baseline (32  degrees C) and following application of local
      controlled heat (43  degrees C) on the upper arm, where the patch was placed. The
      residue of the nicotine patches was then examined by High-Performance Liquid
      Chromatography (HPLC) to indicate the uptake of nicotine from the patch due to
      the local controlled heat. Controlled heat application (43 degrees C) caused
      significant cutaneous hyperaemia (up to 9 folds increase in skin perfusion) with
      an increase in nicotine uptake (up to 13 folds). The method was well tolerated
      without causing any pain or discomfort. These data suggest that controlled heat
      application, which is a simple, non-invasive method, can significantly enhance
      local skin perfusion and drug uptake from patches.

PMID- 21941615
TI  - Monographs editor: manel esteller.

PMID- 21941613
TI  - The role of GABAergic system in neurodevelopmental disorders: a focus on autism
      and epilepsy.
AB  - Autism spectrum disorders (ASD) and epilepsy are very common neurological
      disorders of childhood, with an estimated incidence of about 0.5 - 1 % in
      worldwide population. ASD and epilepsy are often associated, suggesting that
      common neurodevelopmental bases may exist for these two disorders. The
      neurodevelopmental bases of both ASD and epilepsy have been clearly showed by a
      number of genetic, neuroimaging and neuropathological studies. In recent years,
      dysfunction of inhibitory GABAergic circuits has been proposed as a cause for
      both disorders. Several studies performed on both animal models and postmortem
      human samples indicate that GABAergic neurons and circuits are altered in both
      ASD and epilepsy, suggesting that the excitation/inhibition imbalance resulting
      from neurodevelopmental defects in GABAergic circuitry might represent a common
      pathogenetic mechanism for these disorders. Here, we will review the most
      significant studies supporting this hypothesis.

PMID- 21941616
TI  - Cancer Epigenetics for the 21st Century: What's Next?
AB  - The discovery of global DNA hypomethylation events in human tumors in the early
      1980s and the identification of CpG island promoter hypermethylation of tumor
      suppressor genes in cancer cells in the mid 1990s opened the door to the current
      excitement about the contribution of epigenetic disruption to human disease. The
      recent gigantic advances in technology make it possible to obtain complete DNA
      methylomes, histonomes, and non-coding RNA transcriptomes for many biological
      settings and their associated disorders. Furthermore, whole genome sequencing
      analyses yields an increasing number of mutated epigenetic genes in neoplasia. It
      is time to sit back, enjoy the show with a little help of friendly bioinformatic
      tools, and wonder about what will happen next.

PMID- 21941617
TI  - DNA methylation: superior or subordinate in the epigenetic hierarchy?
AB  - Epigenetic modifications are heritable changes in gene expression not encoded by
      the DNA sequence. In the past decade, great strides have been made in
      characterizing epigenetic changes during normal development and in disease states
      like cancer. However, the epigenetic landscape has grown increasingly
      complicated, encompassing DNA methylation, the histone code, noncoding RNA, and
      nucleosome positioning, along with DNA sequence. As a stable repressive mark, DNA
      methylation, catalyzed by the DNA methyltransferases (DNMTs), is regarded as a
      key player in epigenetic silencing of transcription. DNA methylation may
      coordinately regulate the chromatin status via the interaction of DNMTs with
      other modifications and with components of the machinery mediating those marks.
      In this review, we will comprehensively examine the current understanding of the
      connections between DNA methylation and other epigenetic marks and discuss
      molecular mechanisms of transcriptional repression in development and in
      carcinogenesis.

PMID- 21941618
TI  - The Roles of the Methyl-CpG Binding Proteins in Cancer.
AB  - The methyl-CpG binding proteins (MBPs) interpret the methylation of DNA and its
      components. The number of MBPs in the human body currently stands at 15, which
      are split into 3 branches, a reflection of the intricate mechanisms of gene
      regulation. Each branch utilizes a different mechanism for interacting with
      methylated DNA or its components. These interactions function to direct gene
      expression and maintain or alter DNA architecture. It is these functions that are
      commonly exploited in human disease. For this review, we will focus on each
      protein and any roles it may have in initiating, promoting, progressing, or
      inhibiting cancer. This will highlight common threads in the roles of these
      proteins, which will allow us to speculate on potentially productive directions
      for future research.

PMID- 21941621
TI  - Targeting Histone Demethylases: A New Avenue for the Fight against Cancer.
AB  - In addition to genetic disorders, epigenetic alterations have been shown to be
      involved in cancer, through misregulation of histone modifications. Miswriting,
      misreading, and mis-erasing of histone acetylation as well as methylation marks
      can be actually associated with oncogenesis and tumor proliferation.
      Historically, methylation of Arg and Lys residues has been considered a stable,
      irreversible process due to the slow turnover of methyl groups in chromatin. The
      discovery in recent years of a large number of histone Lys demethylases (KDMs,
      belonging to either the amino oxidase or the JmjC family) totally changed this
      point of view and suggested a new role for dynamic histone methylation in
      biological processes. Since overexpression, alteration, or mutation of a number
      of KDMs has been found in many types of cancers, such enzymes could represent
      diagnostic tools as well as epigenetic targets to modulate for obtaining novel
      therapeutic weapons against cancer. The first little steps in this direction are
      described here.

PMID- 21941619
TI  - Histone modifiers in cancer: friends or foes?
AB  - Covalent modifications of histones can regulate all DNA-dependent processes. In
      the last few years, it has become more and more evident that histone
      modifications are key players in the regulation of chromatin states and dynamics
      as well as in gene expression. Therefore, histone modifications and the enzymatic
      machineries that set them are crucial regulators that can control cellular
      proliferation, differentiation, plasticity, and malignancy processes. This review
      discusses the biology and biochemistry of covalent histone posttranslational
      modifications (PTMs) and evaluates the dual role of their modifiers in cancer: as
      oncogenes that can initiate and amplify tumorigenesis or as tumor suppressors.

PMID- 21941620
TI  - The dual role of sirtuins in cancer.
AB  - Among the greatest challenges facing organisms is that of detecting and
      effectively responding to life-threatening environmental changes that are
      intimately associated with metabolic fluctuations and certain forms of stress.
      These conditions have been linked to the onset of many human pathologies,
      including cancer. Over the past decade, members of the Sir2 family, or sirtuins,
      have been described as major players in sensing and coordinating stress response.
      Evidence has imputed mammalian sirtuins in carcinogenesis, although the
      mechanisms involved seem to be more diverse and complex than previously
      anticipated. Some sirtuins, such as SirT2 and SirT6, seem to work as tumor
      suppressors, but others, such as SirT1, are apparently bifunctional: operating as
      both tumor suppressors and oncogenic factors depending on the context and the
      study conditions. The mechanisms underlying these apparently contradictory
      activities are not well understood, although recent findings suggest that they
      might actually be two sides of the same coin. In this review, the authors
      summarize current knowledge on the functional implications of sirtuins in cancer
      and discuss possible explanations for their functional duality.

PMID- 21941622
TI  - The decade of the epigenomes?
AB  - The beginning of this century was not only marked by the publication of the first
      draft of the human genome but also set off a decade of intense research on
      epigenetic phenomena. Apart from DNA methylation, it became clear that many other
      factors including a wide range of histone modifications, different shades of
      chromatin accessibility, and a vast suite of noncoding RNAs comprise the
      epigenome. With the recent advances in sequencing technologies, it has now become
      possible to analyze many of these features in depth, allowing for the first time
      the establishment of complete epigenomic profiles for basically every cell type
      of interest. Here, we will discuss the recent advances that allow comprehensive
      epigenetic mapping, highlight several projects that set out to better understand
      the epigenome, and discuss the impact that epigenomic mapping can have on our
      understanding of both healthy and diseased cells.

PMID- 21941623
TI  - A long-awaited structure is rev-ealed.
AB  - It has been known for some time that the HIV Rev protein binds and oligomerizes
      on a well-defined multiple stem-loop RNA structure, named the Rev Response
      Element (RRE), which is present in a subset of HIV mRNAs. This binding is the
      first step in a pathway that overcomes a host restriction, which would otherwise
      prevent the export of these RNAs to the cytoplasm. Four recent publications now
      provide new insight into the structure of Rev and the multimeric RNA-protein
      complex that forms on the RRE. Two unexpected and remarkable findings revealed in
      these studies are the flexibility of RNA binding that is demonstrated by the Rev
      arginine-rich RNA binding motif, and the way that both Rev protein and RRE
      contribute to the formation of the complex in a highly cooperative fashion. These
      studies also define the Rev dimerization and oligomerization interfaces to a
      resolution of 2.5A, providing a framework necessary for further structural and
      functional studies. Additionally, and perhaps most importantly, they also pave
      the way for rational drug design, which may ultimately lead to new therapies to
      inhibit this essential HIV function.

PMID- 21941624
TI  - The alpha-melanocyte stimulating hormone induces conversion of effector T cells
      into treg cells.
AB  - The neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) has an
      important role in modulating immunity and homeostasis. The production of IFN
      gamma by effector T cells is suppressed by alpha-MSH, while TGF-beta production
      is promoted in the same cells. Such alpha-MSH-treated T cells have immune
      regulatory activity and suppress hypersensitivity, autoimmune diseases, and graft
      rejection. Previous characterizations of the alpha-MSH-induced Treg cells showed
      that the cells are CD4(+) T cells expressing the same levels of CD25 as effector
      T cells. Therefore, we further analyzed the alpha-MSH-induced Treg cells for
      expression of effector and regulatory T-cell markers. Also, we examined the
      potential for alpha-MSH-induced Treg cells to be from the effector T-cell
      population. We found that the alpha-MSH-induced Treg cells are CD25(+)  CD4(+) T
      cells that share similar surface markers as effector T cells, except that they
      express on their surface LAP. Also, the alpha-MSH treatment augments FoxP3
      message in the effector T cells, and alpha-MSH induction of regulatory activity
      was limited to the effector CD25(+) T-cell population. Therefore, alpha-MSH
      converts effector T cells into Treg cells, which suppress immunity targeting
      specific antigens and tissues.

PMID- 21941625
TI  - Real and pseudoaccommodation in accommodative lenses.
AB  - In the attempt to manage presbyopia, different intraocular lens designs have been
      proposed such as monofocal IOLs with monovision or multifocal IOLs. Even though
      the lenses mentioned offer satisfactory visual results, contemporary
      ophthalmology has not completely answered the presbyopic dilemma by simulating
      the accommodative properties of the crystalline lens itself. Accommodative IOLs
      were designed to fill this gap and provide satisfactory vision for all distances
      by restoring some degree of "pseudoaccommodation." Pseudo accommodative
      capability can be linked to monofocal IOL's as well but the results are not
      satisfactory enough to fully support unaided near vision. Pseudoaccommodation is
      a complex phenomenon that can be attributed to several static (i.e., pupil size,
      against-the-rule cylindrical refractive error, multifocality of the cornea) and
      dynamic (i.e., anterior movement of the implant itself) factors. Objective
      measurement of the accommodative capability offered by the accommodative IOLs is
      extremely difficult to obtain, and different methods such as autorefractometers,
      retinoscopy, and ultrasound imaging during accommodative effort, ray tracing, or
      pharmacological stimulation have been developed but the results are sometimes
      inconsistent. Despite the difficulties in measuring accommodation, accommodative
      IOLs represent the future in the attempt to successfully "cure" presbyopia.

PMID- 21941626
TI  - New technologies for glaucoma imaging.

PMID- 21941627
TI  - Photoswitching of site-selective RNA scission by sequential incorporation of
      azobenzene and acridine residues in a DNA oligomer.
AB  - Photoresponsive systems for site-selective RNA scission have been prepared by
      combining Lu(III) ions with acridine/azobenzene dual-modified DNA. The modified
      DNA forms a heteroduplex with substrate RNA, and the target phosphodiester
      linkages in front of the acridine residue is selectively activated so that
      Lu(III) ion rapidly cleaves the linkage. Azobenzene residue introduced adjacent
      to the acridine residue acts as a photoresponsive switch, which triggers the site
      selective scission upon UV irradiation. A trans isomer of azobenzene efficiently
      suppresses the scission, whereas the cis isomer formed by UV irradiation hardly
      affects the scission. As a result, 1.7-2.4-fold acceleration of the cleavage was
      achieved simply by irradiating UV for 3 min to the mixture prior to the reaction.
      Considering the yield of photoisomerization, the intrinsic activity of a cis
      isomer is up to 14.5-fold higher than that of the trans isomer.

PMID- 21941628
TI  - Direct detection of thrombin binding to 8-bromodeoxyguanosine-modified aptamer:
      effects of modification on affinity and kinetics.
AB  - The affinity of an 8-bromodeoxyguanosine- (8-BrdG-) substituted thrombin-binding
      aptamer (TBA-Br), which has the 1st and 10th guanosine residues replaced with 8
      BrdG, was estimated using reflectometric interference spectroscopy (RIfS). When
      comparing TBA-Br with unmodified TBA (TBA-H), it was demonstrated that the
      modification effectively improved the affinity of TBA; dissociation constants
      (K(D)) of TBA-H and TBA-Br were 45.4 nM and 1.99 nM, respectively. These values,
      which were obtained by direct observation of thrombin binding using RIfS, have
      the same order of magnitude as those obtained in our previous study utilizing
      conformational changes in TBA to detect thrombin binding, thus confirming the
      validity of the obtained K(D) values. RIfS measurements also revealed that the 8
      BrdG modification resulted in a lower dissociation rate constant (k(d)), which
      suggests that the enhancement of affinity can be attributed to the stabilization
      of the G-quadruplex structure on introduction of 8-BrdG.

PMID- 21941629
TI  - A structurally variable hinged tetrahedron framework from DNA origami.
AB  - Nanometer-sized polyhedral wire-frame objects hold a wide range of potential
      applications both as structural scaffolds as well as a basis for synthetic
      nanocontainers. The utilization of DNA as basic building blocks for such
      structures allows the exploitation of bottom-up self-assembly in order to achieve
      molecular programmability through the pairing of complementary bases. In this
      work, we report on a hollow but rigid tetrahedron framework of 75 nm strut length
      constructed with the DNA origami method. Flexible hinges at each of their four
      joints provide a means for structural variability of the object. Through the
      opening of gaps along the struts, four variants can be created as confirmed by
      both gel electrophoresis and direct imaging techniques. The intrinsic site
      addressability provided by this technique allows the unique targeted attachment
      of dye and/or linker molecules at any point on the structure's surface, which we
      prove through the superresolution fluorescence microscopy technique DNA PAINT.

PMID- 21941630
TI  - Triplet Analysis That Identifies Unpaired Regions of Functional RNAs.
AB  - We developed a novel method for analyzing RNA sequences, deemed triplet analysis,
      and applied the method in an in vitro RNA selection experiment in which HIV-1 Tat
      was the target. Aptamers are nucleic acids that bind a desired target (bait), and
      to date, many aptamers have been identified by in vitro selection from enough
      concentrated libraries in which many RNAs had an obvious consensus primary
      sequence after sufficient cycles of the selection. Therefore, the higher-order
      structural features of the aptamers that are indispensable for interaction with
      the bait must be determined by additional investigation of the aptamers. In
      contrast, our triplet analysis enabled us to extract important information on
      functional primary and secondary structure from minimally concentrated RNA
      libraries. As a result, by using our method, an important unpaired region that is
      similar to the bulge of TAR was readily predicted from a partially concentrated
      library in which no consensus sequence was revealed by a conventional sequence
      analysis. Moreover, our analysis method may be used to assess a variety of
      structural motifs with desired function.

PMID- 21941631
TI  - Enzymatic Synthesis of the Flavone Glucosides, Prunin and Isoquercetin, and the
      Aglycones, Naringenin and Quercetin, with Selective alpha-L-Rhamnosidase and beta
      D-Glucosidase Activities of Naringinase.
AB  - The production of flavonoid glycosides by removing rhamnose from rutinosides can
      be accomplished through enzymatic catalysis. Naringinase is an enzyme complex,
      expressing both alpha-L-rhamnosidase and beta-D-glucosidase activities, with
      application in glycosides hydrolysis. To produce monoglycosylated flavonoids with
      naringinase, the expression of beta-D-glucosidase activity is not desirable
      leading to the need of expensive methods for alpha-L-rhamnosidase purification.
      Therefore, the main purpose of this study was the inactivation of beta-D
      glucosidase activity expressed by naringinase keeping alpha-L-rhamnosidase with a
      high retention activity. Response surface methodology (RSM) was used to evaluate
      the effects of temperature and pH on beta-D-glucosidase inactivation. A selective
      inactivation of beta-D-glucosidase activity of naringinase was achieved at 81.5
      degrees C and pH 3.9, keeping a very high residual activity of alpha-L
      rhamnosidase (78%). This was a crucial achievement towards an easy and cheap
      production method of very expensive flavonoids, like prunin and isoquercetin
      starting from naringin and rutin, respectively.

PMID- 21941632
TI  - Lignolytic Enzymes of a Mushroom Stereum ostrea Isolated from Wood Logs.
AB  - Production of lignolytic enzymes by the mushroom fungus Stereum ostrea in liquid
      medium under conditions of vegetative growth was examined for 10 days in
      comparison to the reference culture Phanerochaete chrysosporium. Though growth
      and secretion of extracellular protein by S. ostrea were comparable to those of
      P. chrysosporium, yields of laccase enzyme by S. ostrea were higher than laccase
      titres of P. chrysosporium by more than 2 folds on the peak production time
      interval (IVth day of incubation). S. ostrea yielded titres of 25 units of
      laccase/ml as against 8.9 units of laccase/ml on the IVth day of incubation.
      Stereum ostrea also exhibited activities of other lignolytic enzymes, lignin
      peroxidase (LiP) and manganese peroxidase (MnP), higher than the reference
      culture. Growth of S. ostrea on the medium in the presence of Remazol orange 16
      resulted in the decolourisation of dye, confirming the presence of lignolytic
      enzymes. S. ostrea appears to be a promising culture with complete lignolytic
      system.

PMID- 21941633
TI  - Novel strategies for upstream and downstream processing of tannin acyl hydrolase.
AB  - Tannin acyl hydrolase also referred as tannase is an enzyme with important
      applications in several science and technology fields. Due to its hydrolytic and
      synthetic properties, tannase could be used to reduce the negative effects of
      tannins in beverages, food, feed, and tannery effluents, for the production of
      gallic acid from tannin-rich materials, the elucidation of tannin structure, and
      the synthesis of gallic acid esters in nonaqueous media. However, industrial
      applications of tannase are still very limited due to its high production cost.
      Thus, there is a growing interest in the production, recovery, and purification
      of this enzyme. Recently, there have been published a number of papers on the
      improvement of upstream and downstream processing of the enzyme. These papers
      dealt with the search for new tannase producing microorganisms, the application
      of novel fermentation systems, optimization of culture conditions, the production
      of the enzyme by recombinant microorganism, and the design of efficient protocols
      for tannase recovery and purification. The present work reviews the state of the
      art of basic and biotechnological aspects of tannin acyl hydrolase, focusing on
      the recent advances in the upstream and downstream processing of the enzyme.

PMID- 21941634
TI  - Kinetic Characterisation of Phosphofructokinase Purified from Setaria cervi: A
      Bovine Filarial Parasite.
AB  - Phosphofructokinase (PFK), a regulatory enzyme in glycolytic pathway, has been
      purified to electrophoretic homogeneity from adult female Setaria cervi and
      partially characterized. For this enzyme, the Lineweaver-Burk's double reciprocal
      plots of initial rates and D-fructose-6-phosphate (F-6-P) or Mg-ATP
      concentrations for varying values of cosubstrate concentration gave intersecting
      lines indicating that K(m) values for F-6-P (1.05 mM) and ATP (3 MUM) were
      independent of each other. S. cervi PFK, when assayed at inhibitory concentration
      of ATP (>0.1 mM), exhibited sigmoidal behavior towards binding with F-6-P with a
      Hill coefficient (n) value equal to 1.8 and 1.7 at 1.0 and 0.33 mM ATP,
      respectively. D-fructose-1,6-diphosphate (FDP) competitively inhibited the
      filarial enzyme: K(i) and Hill coefficient values being 0.18 MUM and 2.0,
      respectively. Phosphoenolpyruvate (PEP) also inhibited the enzyme competitively
      with the K(i) value equal to 0.8 mM. The Hill coefficient values (>1.5) for F-6-P
      (at inhibitory concentration of ATP) and FDP suggested its positive cooperative
      kinetics towards F-6-P and FDP, showing presence of more than one binding sites
      for these molecules in enzyme protein and allosteric nature of the filarial
      enzyme. The product inhibition studies gave us the only compatible mechanism of
      random addition process with a probable orientation of substrates and products on
      the enzyme surface.

PMID- 21941635
TI  - Overweight and obesity in eastern mediterranean region: prevalence and possible
      causes.
AB  - The objective of this paper was to explore the prevalence of overweight and
      obesity among various age groups as well as discuss the possible factors that
      associated with obesity in the Eastern Mediterranean Region (EMR). A systematic
      review of published papers between 1990 and 2011 was carried out. Obesity reached
      an alarming level in all age groups of the EMR countries. The prevalence of
      overweight among preschool children(<5 years) ranged from 1.9% to 21.9%, while
      the prevalence of overweight and obesity among school children ranged from 7% to
      45%. Among adults the prevalence of overweight and obesity ranged from 25% to
      81.9%. Possible factors determining obesity in this region include: nutrition
      transition, inactivity, urbanization, marital status, a shorter duration of
      breastfeeding, frequent snacking, skipping breakfast, a high intake of sugary
      beverages, an increase in the incidence of eating outside the home, long periods
      of time spent viewing television, massive marketing promotion of high fat foods,
      stunting, perceived body image, cultural elements and food subsidize policy. A
      national plan of action to overcome obesity is urgently needed to reduce the
      economic and health burden of obesity in this region.

PMID- 21941636
TI  - Dairy Foods in a Moderate Energy Restricted Diet Do Not Enhance Central Fat,
      Weight, and Intra-Abdominal Adipose Tissue Losses nor Reduce Adipocyte Size or
      Inflammatory Markers in Overweight and Obese Adults: A Controlled Feeding Study.
AB  - Background. Research on dairy foods to enhance weight and fat loss when
      incorporated into a modest weight loss diet has had mixed results. Objective. A
      15-week controlled feeding study to determine if dairy foods enhance central fat
      and weight loss when incorporated in a modest energy restricted diet of
      overweight and obese adults. Design. A 3-week run-in to establish energy needs; a
      12-week 500 kcal/d energy reduction with 71 low-dairy-consuming overweight and
      obese adults randomly assigned to diets: <=1 serving dairy/d (low dairy, LD) or
      <=4 servings dairy/d (adequate dairy, AD). All foods were weighed and provided by
      the metabolic kitchen. Weight, fat, intra-abdominal adipose tissue (IAAT),
      subcutaneous adipose tissue (SAT) macrophage number, SAT inflammatory gene
      expression, and circulating cytokines were measured. Results. No diet differences
      were observed in weight, fat, or IAAT loss; nor SAT mRNA expression of
      inflammation, circulating cytokines, fasting lipids, glucose, or insulin. There
      was a significant increase (P = 0.02) in serum 25-hydroxyvitamin D in the AD
      group. Conclusion. Whether increased dairy intake during weight loss results in
      greater weight and fat loss for individuals with metabolic syndrome deserves
      investigation. Assessment of appetite, hunger, and satiety with followup on
      weight regain should be considered.

PMID- 21941637
TI  - Diet and exercise in the treatment of Fatty liver.

PMID- 21941638
TI  - Resting Energy Expenditure in Anorexia Nervosa: Measured versus Estimated.
AB  - Introduction. Aim of this study was to compare the resting energy expenditure
      (REE) measured by the Douglas bag method with the REE estimated with the FitMate
      method, the Harris-Benedict equation, and the Muller et al. equation for
      individuals with BMI < 18.5 kg/m(2) in a severe group of underweight patients
      with anorexia nervosa (AN). Methods. 15 subjects with AN participated in the
      study. The Douglas bag method and the FitMate method were used to measure REE and
      the dual energy X-ray absorptiometry to assess body composition after one day of
      refeeding. Results. FitMate method and the Muller et al. equation gave an
      accurate REE estimation, while the Harris-Benedict equation overestimated the REE
      when compared with the Douglas bag method. Conclusion. The data support the use
      of the FitMate method and the Muller et al. equation, but not the Harris-Benedict
      equation, to estimate REE in AN patients after short-term refeeding.

PMID- 21941639
TI  - Effects on metabolic health after a 1-year-lifestyle intervention in overweight
      and obese children: a randomized controlled trial.
AB  - Objective. To evaluate the effect of a family-based intervention on
      anthropometric and metabolic markers in overweight and obese children. Methods.
      Overweight or obese 8-12 years olds (n = 93) were randomized into intervention or
      control groups. The intervention group participated in a program aiming for
      lifestyle changes regarding food habits and physical activity. Anthropometric
      measures and venous blood samples were collected from all children at baseline
      and after 1 year. Results. BMI z-scores decreased in both groups, 0.22 (P =
      0.002) and 0.23 (P = 0.003) in intervention and control group, respectively,
      during the 1-year study, but there was no difference in BMI between the groups at
      1-year measurement (P = 0.338). After 1 year, there was a significant difference
      in waist circumference, waist/hip ratio, and apolipoprotein B/A1 ratio between
      intervention and control group. Conclusions. The intervention had limited effects
      on anthropometrics and metabolic markers, which emphasizes the need of preventing
      childhood overweight and obesity.

PMID- 21941640
TI  - CD4 Cell Counts at HIV Diagnosis among HIV Outpatient Study Participants, 2000
      2009.
AB  - Background. It is unclear if CD4 cell counts at HIV diagnosis have improved over
      a 10-year period of expanded HIV testing in the USA. Methods. We studied HOPS
      participants diagnosed with HIV infection <=6 months prior to entry into care
      during 2000-2009. We assessed the correlates of CD4 count <200 cells/mm(3) at HIV
      diagnosis (late HIV diagnosis) by logistic regression. Results. Of 1,203 eligible
      patients, 936 (78%) had a CD4 count within 3 months after HIV diagnosis. Median
      CD4 count at HIV diagnosis was 299 cells/mm(3) and did not significantly improve
      over time (P = 0.13). Comparing periods 2000-2001 versus 2008-2009, respectively,
      39% and 35% of patients had a late HIV diagnosis (P = 0.34). Independent
      correlates of late HIV diagnosis were having an HIV risk other than being MSM,
      age >=35 years at diagnosis, and being of nonwhite race/ethnicity. Conclusions.
      There is need for routine universal HIV testing to reduce the frequency of late
      HIV diagnosis and increase opportunity for patient- and potentially population
      level benefits associated with early antiretroviral treatment.

PMID- 21941642
TI  - Revisiting Shimoda's "Shuuchaku-Kishitsu" (Statothymia): A Japanese View of Manic
      Depressive Patients.
AB  - Although the empiric paradigm is now dominant in academic research, in Japan
      quite a few psychiatric clinicians still take phenomenological-anthropological
      approaches into consideration, especially when they address manic-depressive
      illness with typical endogenous features. This is because Shimoda's concept of
      "shuuchaku-kishitsu" (statothymia) has been widely accepted, together with other
      phenomenological views of continental origin. In the present paper the author
      first delineates Shimoda's concept which is based on observations of patients'
      personality features and the characteristics of their emotionality. He then
      attempts to refine this concept in spatiotemporal terms, presenting the view that
      in patients the past self tends to adhere to the present self (the term
      "shuuchaku" means "adhering to" or "preoccupied with"). He also considers that
      patients tend to incorporate "soto" (outer space) into "uchi" (inner space),
      where they believe that symbiotic relations are preserved. Finally, he argues the
      clinical significance of the presented views in the cultural milieu in which
      Japanese psychiatric practices are situated.

PMID- 21941641
TI  - APOE and FABP2 Polymorphisms and History of Myocardial Infarction, Stroke,
      Diabetes, and Gallbladder Disease.
AB  - Dysfunctional lipid metabolism plays a central role in pathogenesis of major
      chronic diseases, and genetic factors are important determinants of individual
      lipid profiles. We analyzed the associations of two well-established functional
      polymorphisms (FABP2 A54T and APOE isoforms) with past and family histories of
      1492 population samples. FABP2-T54 allele was associated with an increased risk
      of past history of myocardial infarction (odds ratio (OR) = 1.51). Likewise, the
      subjects with APOE4, compared with E2 and E3, had a significantly increased risk
      of past history myocardial infarction (OR = 1.89). The OR associated with APOE4
      was specifically increased in women for past history of myocardial infarction but
      decreased for gallstone disease. Interactions between gender and APOE isoforms
      were also significant or marginally significant for these two conditions. FABP2
      T54 allele may be a potential genetic marker for myocardial infarction, and APOE4
      may exert sex-dependent effects on myocardial infarction and gallbladder disease.

PMID- 21941643
TI  - More Similar than Different? Exploring Cultural Models of Depression among Latino
      Immigrants in Florida.
AB  - The Surgeon General's report, "Culture, Race, and Ethnicity: A Supplement to
      Mental Health," points to the need for subgroup specific mental health research
      that explores the cultural variation and heterogeneity of the Latino population.
      Guided by cognitive anthropological theories of culture, we utilized ethnographic
      interviewing techniques to explore cultural models of depression among foreign
      born Mexican (n = 30), Cuban (n = 30), Columbian (n = 30), and island-born Puerto
      Ricans (n = 30), who represent the largest Latino groups in Florida. Results
      indicate that Colombian, Cuban, Mexican, and Puerto Rican immigrants showed
      strong intragroup consensus in their models of depression causality, symptoms,
      and treatment. We found more agreement than disagreement among all four groups
      regarding core descriptions of depression, which was largely unexpected but can
      potentially be explained by their common immigrant experiences. Findings expand
      our understanding about Latino subgroup similarities and differences in their
      conceptualization of depression and can be used to inform the adaptation of
      culturally relevant interventions in order to better serve Latino immigrant
      communities.

PMID- 21941644
TI  - Factors Influencing Depression and Anxiety among Black Sexual Minority Men.
AB  - The primary aim of this study was to examine the relationships between depression
      and anxiety, and ethnic and sexual identity development, and discrimination and
      harassment (DH) among Black sexual minority men. Additional aims were to
      determine whether an interaction effect existed between ethnic and sexual
      identity and whether coping skills level moderated these relationships. Using an
      observational cross-sectional design, 54 participants recruited through snowball
      sampling completed self-administered online surveys. Stepwise multiple regression
      analysis was used. Sixty-four percent of the variance in depression scores and
      53% of the variance in anxiety scores were explained by DH and internalized
      homonegativity together. Thirty percent of the sample had scale scores indicating
      likelihood of depression and anxiety. Experience of DH and internalized
      homonegativity explained a large portion of the variability in depression and
      anxiety among Black sexual minority men. The study showed high prevalence of
      mental distress among this sample.

PMID- 21941645
TI  - Etiology and Viral Genotype in Patients with End-Stage Liver Diseases admitted to
      a Hepatology Unit in Colombia.
AB  - Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are the principal
      risk factor associated to end-stage liver diseases in the world. A study was
      carried out on end-stage liver disease cases admitted to an important hepatology
      unit in Medellin, the second largest city in Colombia. From 131 patients
      recruited in this prospective study, 71% of cases were diagnosed as cirrhosis,
      12.2% as HCC, and 16.8% as cirrhosis and HCC. Regarding the risk factors of these
      patients, alcohol consumption was the most frequent (37.4%), followed by viral
      etiology (17.6%). Blood and/or hepatic tissue samples from patients with
      serological markers for HCV or HBV infection were characterized; on the basis of
      the phylogenetic analysis of HCV 5' UTR and HBV S gene, isolates belonged to
      HCV/1 and HBV/F3, respectively. These results confirm the presence of strains
      associated with poor clinical outcome, in patients with liver disease in
      Colombia; additionally, HBV basal core promoter double mutant was identified in
      HCC cases. Here we show the first study of cirrhosis and/or HCC in Colombian and
      HBV and HCV molecular characterization of these patients. Viral aetiology was not
      the main risk factor in this cohort but alcohol consumption.

PMID- 21941646
TI  - Role of Stress Myocardial Scintigraphy in the Evaluation of Incompletely
      Revascularized Post-PCI Patients.
AB  - Percutaneous coronary intervention (PCI) is actually the most used method of
      revascularization. Although complete revascularization remains a desirable goal,
      it may not be possible or not easy to plan in many patients. Thus, incomplete
      revascularization might be a preferred treatment strategy in selected patient
      categories. Stress myocardial scintigraphy, because of its high diagnostic
      accuracy and prognostic value and its ability to assess location and extent of
      myocardial ischemia regardless of symptoms as well as to evaluate patients who
      are unable to exercise or who have uninterpretable electrocardiogram, is of
      paramount importance for clinical decision making in patients with multivessel
      disease and incomplete revascularization.

PMID- 21941647
TI  - Towards in vivo imaging of cancer sialylation.
AB  - In vivo assessment of tumor glucose catabolism by positron emission tomography
      (PET) has become a highly valued study in the medical management of cancer.
      Emerging technologies offer the potential to evaluate in vivo another aspect of
      cancer carbohydrate metabolism related to the increased anabolic use of
      monosaccharides like sialic acid (Sia). Sia is used for the synthesis of
      sialylated oligosaccharides in the cell surface that in cancer cells are
      overexpressed and positively associated to malignancy and worse prognosis because
      of their role in invasion and metastasis. This paper addresses the key points of
      the different strategies that have been developed to image Sia expression in vivo
      and the perspectives to translate it from the bench to the bedside where it would
      offer the clinician highly valued complementary information on cancer
      carbohydrate metabolism that is currently unavailable in vivo.

PMID- 21941648
TI  - Noninvasive in vivo quantification of neutrophil elastase activity in acute
      experimental mouse lung injury.
AB  - We developed a neutrophil elastase-specific near-infrared fluorescence imaging
      agent, which, combined with fluorescence molecular tomographic imaging, allowed
      us to detect and quantify neutrophil elastase activity in vivo, in real time, and
      noninvasively in an acute model of lung injury (ALI). Significantly higher
      fluorescent signal was quantified in mice with LPS/fMLP-induced ALI as compared
      to healthy controls, correlating with increases in the number of bronchoalveolar
      lavage cells, neutrophils, and elastase activity. The agent was significantly
      activated ex vivo in lung sections from ALI but not from control mice, and this
      activation was ablated by the specific inhibitor sivelestat. Treatment with the
      specific inhibitor sivelestat significantly reduced lung signal in mice with ALI.
      These results underscore the unique ability of fluorescence molecular imaging to
      quantify specific molecular processes in vivo, crucial for understanding the
      mechanisms underlying disease progression and for assessing and monitoring novel
      pharmacological interventions.

PMID- 21941649
TI  - Long-Term Oxygen Therapy in COPD: Factors Affecting and Ways of Improving Patient
      Compliance.
AB  - Long-term oxygen therapy (LTOT) is the cornerstone mode of treatment in patients
      with severe chronic obstructive pulmonary disease (COPD) associated with resting
      hypoxaemia. When appropriately prescribed and correctly used, LTOT has clearly
      been shown to improve survival in hypoxemic COPD patients. Adherence to LTOT
      ranges from 45% to 70% and utilization for more than 15 hours per day is widely
      accepted as efficacious. Although several studies have addressed the level of
      patients' adherence to LTOT, few have suggested or evaluated interventions that
      conduce to compliance enhancement. The lack of sufficient data regarding COPD
      patients following oxygen prescription is an enormous void that must be duly
      confronted to augment clinical effectiveness and cost containment for the long
      term use. The present review article highlights factors influencing the
      compliance of patients using LTOT and emphasizes novel strategies and
      interventions that may prove to be of significant benefit given the remarkably
      little current research appraising this issue. Therefore, additional research
      should be promptly performed to verify the efficacy of newly designed approaches
      in improving the outcomes of patients receiving LTOT.

PMID- 21941650
TI  - Diagnosis and management of pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension is a rare disease, which requires a high index of
      suspicion to diagnose when patients initially present. Initial symptoms can be
      nonspecific and include complaints such as fatigue and mild dyspnea. Once the
      disease is suspected, echocardiography is used to estimate the pulmonary arterial
      (PA) pressure and to exclude secondary causes of elevated PA pressures such as
      left heart disease. Right heart catheterization with vasodilator challenge is
      critical to the proper assessment of pulmonary hemodynamics and to determine
      whether patients are likely to benefit from vasodilator therapy. Pathologically,
      the disease is characterized by deleterious remodeling of the distal pulmonary
      arterial and arteriolar circulation, which results in increased pulmonary
      vascular resistance. In the last fifteen years, medications from three different
      classes have been approved for the treatment of pulmonary arterial hypertension.
      These include the prostanoids, endothelin receptor antagonists, and
      phosphodiesterase-5 inhibitors.

PMID- 21941651
TI  - Potential application of tregitopes as immunomodulating agents in multiple
      sclerosis.
AB  - The induction of immunologic tolerance is an important clinical goal in
      autoimmunity. CD4(+) regulatory T (Treg) cells, defined by the expression of the
      transcription factor forkhead box P3 (FoxP3), play a central role in the control
      of autoimmune responses. Quantitative and qualitative defects of Tregs have been
      postulated to contribute to failed immune regulation in multiple sclerosis (MS)
      and other autoimmune diseases. This paper highlights the potential uses of T
      regulatory cell epitopes (Tregitopes), natural Treg epitopes found to be
      contained in human immunoglobulins, as immunomodulating agents in MS. Tregitopes
      expand Treg cells and induce "adaptive Tregs" resulting in immunosuppression and,
      therefore, are being considered as a potential therapy for autoimmune diseases.
      We will compare Tregitopes versus intravenous immunoglobulin (IVIg) in the
      treatment of EAE with emphasis on the potential applications of Tregitope for the
      treatment of MS.

PMID- 21941652
TI  - Incremental peritoneal dialysis favourably compares with hemodialysis as a bridge
      to renal transplantation.
AB  - Background. The value of incremental peritoneal dialysis (PD) as a bridge to
      renal transplantation (Tx) has not been specifically addressed. Methods. All
      consecutive Stage 5 CKD patients with at least 1 year predialysis followup,
      starting incremental PD or HD under our care and subsequently receiving their
      first renal Tx were included in this observational cohort study. Age, gender,
      BMI, underlying nephropathy, residual renal function (RRF) loss rate before
      dialysis and RRF at RRT start, comorbidity, RRT schedules and adequacy measures,
      dialysis-related morbidity, Tx waiting time, RRF at Tx, incidence of delayed
      graft function (DGF), in-hospital stay for Tx, serum creatinine at discharge and
      one year later were collected and compared between patients on incremental PD or
      HD before Tx. Results. Seventeen patients on incremental PD and 24 on HD received
      their first renal Tx during the study period. Age, underlying nephropathy, RRF
      loss rate in predialysis, RRF at the start of RRT and comorbidity did not differ
      significantly. While on dialysis, patients on PD had significantly lower epoetin
      requirements, serum phosphate, calciumxphosphate product and better RRF
      preservation. Delayed graft function (DGF) occurred in 12 patients (29%), 1 on
      incremental PD and 11 on HD. Serum creatinine at discharge and 1 year later was
      significantly higher in patients who had been on HD. Conclusions. In patients
      receiving their first renal Tx, previous incremental PD was associated with low
      morbidity, excellent preservation of RRF, easier attainment of adequacy targets
      and significantly better immediate and 1-year graft function than those observed
      in otherwise well-matched patients previously treated with HD.

PMID- 21941653
TI  - Primary molecular disorders and secondary biological adaptations in bartter
      syndrome.
AB  - Bartter syndrome is a hereditary disorder that has been characterized by the
      association of hypokalemia, alkalosis, and the hypertrophy of the juxtaglomerular
      complex with secondary hyperaldosteronism and normal blood pressure. By contrast,
      the genetic causes of Bartter syndrome primarily affect molecular structures
      directly involved in the sodium reabsorption at the level of the Henle loop. The
      ensuing urinary sodium wasting and chronic sodium depletion are responsible for
      the contraction of the extracellular volume, the activation of the renin
      aldosterone axis, the secretion of prostaglandins, and the biological adaptations
      of downstream tubular segments, meaning the distal convoluted tubule and the
      collecting duct. These secondary biological adaptations lead to hypokalemia and
      alkalosis, illustrating a close integration of the solutes regulation in the
      tubular structures.

PMID- 21941654
TI  - Depressive symptomatology in children and adolescents with chronic renal
      insufficiency undergoing chronic dialysis.
AB  - This paper presents a descriptive study, using the Birleson Scale to determine
      the frequency of depressive symptomatology in children and adolescents with
      chronic renal insufficiency (CRI) undergoing hemodialysis (HD) and chronic
      peritoneal dialysis (CPD). There were 67 patients (40 female and 27 male) with a
      mean age of 14.76 +/- 2.71 years, duration of illness >=3 months, 43 (64.18%)
      patients with CPD and 24 (35.82%) undergoing HD. The frequency of high
      occurrence, low occurrence, and absence of depressive symptomatology was 10.45%
      (n = 7), 43.28% (n = 29), and 46.27% (n = 31), respectively; all of the seven
      (100%) patients with high occurrence of depressive symptomatology were female (P
      = 0.04), and none of these (0%) had a friend to confide in (P = 0.03). Depressive
      symptomatology in patients with CPD was associated with a lower weekly K(t)/V
      compared to those without depressive symptomatology (2.15 +/- 0.68 versus 2.52 +/
      0.65; P = 0.01). There was no association with patient age, caregiver, time and
      dialysis type, anemia, bone disease, nutritional or financial status, origin,
      schooling, or employment.

PMID- 21941655
TI  - Falling less in kansas: development of a fall risk reduction toolkit.
AB  - Falls are a serious health risk for older adults. But for those living in rural
      and frontier areas of the USA, the risks are higher because of limited access to
      health care providers and resources. This study employed a community-based
      participatory research approach to develop a fall prevention toolkit to be used
      by residents of rural and frontier areas without the assistance of health care
      providers. Qualitative data were gathered from both key informant interviews and
      focus groups with a broad range of participants. Data analysis revealed that to
      be effective and accepted, the toolkit should be not only evidence based but also
      practical, low-cost, self-explanatory, and usable without the assistance of a
      health care provider. Materials must be engaging, visually interesting,
      empowering, sensitive to reading level, and appropriate for low-vision users.
      These findings should be useful to other researchers developing education and
      awareness materials for older adults in rural areas.

PMID- 21941656
TI  - Physical Health and Cognitive Function Independently Contributed to Functional
      Disability among Chinese Older Adults: Data from Two Asian Metropolises.
AB  - Objective. We aimed to examine the independent contributions of physical health
      and cognitive function to disability among Chinese older adults living in two
      Asian metropolises and explore the potential influences of environment. Design
      and Participants. Cross-sectional analysis based on data from two population
      based studies: the Shanghai Survey of Alzheimer's Disease and Dementia (n = 4639)
      and the Singapore Longitudinal Ageing Study (n = 2397). Disability was defined as
      needing help in at least one activity of daily living. Results. The prevalence of
      functional disability was higher in Shanghai sample (5%) than that in Singapore
      sample (1.8%). Number of chronic diseases, self-rated health status, cognitive
      function (measured by the Mini-Mental State Examination), and environment
      (Singapore versus Shanghai) significantly contributed to functional disability
      independent of each other. The adjusted Odds Ratio was 1.35 (95%CI 1.22-1.50),
      2.85 (95% CI 2.36-3.43), 0.89 (95% CI 0.85-0.94), and 0.68 (95% CI 0.48-0.96),
      respectively. The strength of associations between health variables and
      disability appeared to be influenced by environment. Conclusion. Physical health
      and cognitive function independently contributed to functional disability. The
      associations are modulated by environmental factors.

PMID- 21941657
TI  - Endocytosis and Sphingolipid Scavenging in Leishmania mexicana Amastigotes.
AB  - Leishmania species are the causative agents of the leishmaniases, a spectrum of
      neglected tropical diseases. Amastigote stage parasites exist within macrophages
      and scavenge host factors for survival, for example, Leishmania species utilise
      host sphingolipid for synthesis of complex sphingolipid. In this study L.
      mexicana endocytosis was shown to be significantly upregulated in amastigotes,
      indicating that sphingolipid scavenging may be enhanced. However, inhibition of
      host sphingolipid biosynthesis had no significant effect on amastigote
      proliferation within a macrophage cell line. In addition, infection itself did
      not directly influence host biosynthesis. Notably, in contrast to L. major, L.
      mexicana amastigotes are indicated to possess a complete biosynthetic pathway
      suggesting that scavenged sphingolipids may be nonessential for proliferation.
      This suggested that Old and New World species differ in their interactions with
      the macrophage host. This will need to be considered when targeting the
      Leishmania sphingolipid biosynthetic pathway with novel therapeutics.

PMID- 21941658
TI  - AT1 Receptor Gene Polymorphisms in relation to Postprandial Lipemia.
AB  - Background. Recent data suggest that the renin-angiotensin system may be involved
      in triglyceride (TG) metabolism. We explored the effect of the common A1166C and
      C573T polymorphisms of the angiotensin II type 1 receptor (AT1R) gene on
      postprandial lipemia. Methods. Eighty-two subjects measured daytime capillary TG,
      and postprandial lipemia was estimated as incremental area under the TG curve.
      The C573T and A1166C polymorphisms of the AT1R gene were determined. Results.
      Postprandial lipemia was significantly higher in homozygous carriers of the 1166
      C allele (9.39 +/- 8.36 mM*h/L) compared to homozygous carriers of the 1166-A
      allele (2.02 +/- 6.20 mM*h/L) (P < 0.05). Postprandial lipemia was similar for
      the different C573T polymorphisms. Conclusion. The 1166-C allele of the AT1R gene
      seems to be associated with increased postprandial lipemia. These data confirm
      the earlier described relationships between the renin-angiotensin axis and
      triglyceride metabolism.

PMID- 21941659
TI  - The contribution of electron paramagnetic resonance to melanoma research.
AB  - The incidence of malignant melanoma, the most dangerous form of skin cancer, is
      rising each year. However, some aspects of the tumor initiation and development
      are still unclear, and the current method of diagnosis, based on the visual
      aspect of the tumor, shows limitations. For these reasons, developments of new
      techniques are ongoing to improve basic knowledge on the disease and diagnosis of
      tumors in individual patients. This paper shows how electron paramagnetic
      resonance (EPR), a method able to detect free radicals trapped in melanin
      pigments, has recently brought its unique value to this specific field. The
      general principles of the method and the convenience of melanin as an endogenous
      substrate for EPR measurements are explained. Then, the way by which EPR has
      recently helped to assess the contribution of ultraviolet rays (UVA and UVB) to
      the initiation of melanoma is described. Finally, we describe the improvements of
      EPR spectrometry and imaging in the detection and mapping of melanin pigments
      inside ex vivo and in vivo melanomas. We discuss how these advances might improve
      the diagnosis of this skin cancer and point out the present capabilities and
      limitations of the method.

PMID- 21941660
TI  - Hydroxyurea therapy mobilises arachidonic Acid from inner cell membrane
      aminophospholipids in patients with homozygous sickle cell disease.
AB  - The cytotoxic compound hydroxyurea (HU) is effective therapy for sickle cell
      disease. However, its effect on unsaturated membrane lipids is unknown. Red cell
      fatty acids were investigated in HU-treated (n = 19) and HU-untreated (n = 17)
      sickle cell patients and controls (n = 20). The HU-treated compared with the HU
      untreated patients had lower arachidonic (AA) acid level in ethanolamine,
      physphoglycerids (EPG) (22.9 +/- 1.2 versus 24.0 +/- 1.1%, P < 0.05) serine SPG
      (22.13 +/- 2.2 versus 24.9 +/- 2.3%, P < 0.01) phosphoglycerides. The treated
      patients and controls had comparable levels of docosahexaenoic (DHA) and total n
      3 fatty acids in EPG and choline phosphoglycerides (CPG). In contrast, the
      untreated group had significantly (P < 0.05) lower DHA and total n-3 compared
      with the controls in EPG (2.7 +/- 0.4 versus 3.2 +/- 0.6% and 4.6 +/- 0.5 versus
      5.2 +/- 0.7%) and CPG (0.7 +/- 0.2 versus 1.0 +/- 0.2% and 1.2 +/- 0.2 versus 1.4
      +/- 0.3). HU is known to activate cytosolic phospholipase A2 and cyclooxygenase
      2, and from this study, it appears to induce mobilisation of AA from the inner
      cell membrane EPG and SPG. Hence, eicosanoids generated from the released AA may
      play a role in clinical improvements which occur in HU-treated patients.

PMID- 21941661
TI  - Anatomy of the Clitoris: Revision and Clarifications about the Anatomical Terms
      for the Clitoris Proposed (without Scientific Bases) by Helen O'Connell,
      Emmanuele Jannini, and Odile Buisson.
AB  - The anatomy of the clitoris is described in human anatomy textbooks. Some
      researchers have proposal and divulged a new anatomical terminology for the
      clitoris. This paper is a revision of the anatomical terms proposed by Helen
      O'Connell, Emmanuele Jannini, and Odile Buisson. Gynecologists, sexual medicine
      experts, and sexologists should spread certainties for all women, not hypotheses
      or personal opinions, they should use scientific terminology:
      clitoral/vaginal/uterine orgasm, G/A/C/U spot orgasm, and female ejaculation, are
      terms that should not be used by sexologists, women, and mass media. Clitoral
      bulbs, clitoral or clitoris-urethrovaginal complex, urethrovaginal space,
      periurethral glans, Halban's fascia erogenous zone, vaginal anterior fornix
      erogenous zone, genitosensory component of the vagus nerve, and G-spot, are terms
      used by some sexologists, but they are not accepted or shared by experts in human
      anatomy. Sexologists should define have sex, make love, the situation in which
      the orgasm happens in both partners with or without a vaginal intercourse.

PMID- 21941662
TI  - Identifying mothers with postpartum depression early: integrating perinatal
      mental health care into the obstetric setting.
AB  - With prevalence rates of postnatal depression (PND) as high as at least 7%, there
      was a need for early detection and intervention of postpartum mental illness
      amongst Singaporean mothers. This is a report on the first year results of our
      country's first PND Intervention Programme. The programme consists of two phases:
      (1) postpartum women were screened with the Edinburgh Postnatal Depression Scale
      and provided appropriate care plans; (2) individualized clinical intervention
      using a case management multidisciplinary team model. Screening for PND was
      generally acceptable, as 64% eligible women participated voluntarily. Nine
      percent (126) were identified as probable cases from 1369 women. Forty-one women
      accepted intervention and achieved 78% reduction in the EPDS symptom scores to
      below the cutoff of 13, 76% had improvement in GAF functioning scores, and 68%
      had improved health quality scores. Preliminary results are promising, and this
      intervention model can be replicated.

PMID- 21941663
TI  - The Role of Demand Factors in Utilization of Professional Care during Childbirth:
      Perspectives from Yemen.
AB  - Background. Utilization of professional care during childbirth by women in low
      income countries is important for the progress towards MDG 5. In Yemen, home
      births have decreased minimally during the past decades. Objective. The study
      investigates the influence of socio-demographic, birth outcome and demand factors
      on women's future preference of a home or institutional childbirth. Method. We
      interviewed 220 women with childbirth experience in urban/rural Yemen. We
      performed bivariate chi-square tests and multiple logistic regression analysis. A
      multistage sampling process was used. Results. The issues of own choice, birth
      support and birth complications were the most important for women's preference of
      future location of childbirth. Women who had previously been able to follow their
      own individual choice regarding birth attendance and/or location of childbirth
      were six times more likely to plan a future childbirth in the same location and
      women who received birth support four times more likely. Birth complications were
      associated with a 2.5-fold decrease in likelihood. Conclusions. To offer women
      with institutional childbirth access to birth support is crucial in attracting
      women to professional care during childbirth. Yemeni women's low utilization of
      modern delivery care should be seen in the context of women's low autonomy and
      status.

PMID- 21941665
TI  - Management of Cardiac Tamponade: A Comperative Study between Echo-Guided
      Pericardiocentesis and Surgery-A Report of 100 Patients.
AB  - Background. Cardiac tamponade (CT) represents a life-threatening condition, and
      the optimal method of draining accumulated pericardial fluid remains
      controversial. We have reviewed 100 patients with CT at our institution over a
      five-year period and compared the results of echo-guided pericardiocentesis,
      primary surgical treatment, and surgical treatment following pericardiocentesis
      with regard to functional outcomes. Methods. The study group consisted of 100
      patients with CT attending Yuzuncu Yil University from January 2005 to January
      2010 who underwent one of the 3 treatment options (echo-guided
      pericardiocentesis, primary surgical treatment, and surgical treatment following
      pericardiocentesis). CT was defined by clinical and echocardiographic criteria.
      Data on medical history, characteristics of the pericardial fluid, treatment
      strategy, and follow-up data were collected. Results. Echo-guided
      pericardiocentesis was performed in 38 (38%) patients (Group A), primary surgical
      treatment was preformed in 36 (36%) patients (Group B), and surgical treatment
      following pericardiocentesis was performed in 26 (26%) patients (Group C).
      Idiopathic and malignant diseases were primary cause of tamponade (28% and 28%,
      resp.), followed by tuberculosis (14%). Total complication rates, 30-day
      mortality, and total mortality rates were highest in Group C. Recurrence of
      tamponade before 90 days was highest in Group A. Conclusions. According to our
      results, minimal invasive procedure echo-guided pericardiocentesis should be the
      first choice because of lower complication and mortality rates especially in
      idiopathic cases and in patients with hemodynamic instability. Surgical approach
      might be performed for traumatic cases, purulent, recurrent, or malign effusions
      with higher complication and mortality rates.

PMID- 21941666
TI  - Optical coherence tomography imaging in acute coronary syndromes.
AB  - Optical coherence tomography (OCT) is a high-resolution imaging technique that
      offers microscopic visualization of coronary plaques. The clear and detailed
      images of OCT generate an intense interest in adopting this technique for both
      clinical and research purposes. Recent studies have shown that OCT is useful for
      the assessment of coronary atherosclerotic plaques, in particular the assessment
      of plaque rupture, erosion, and intracoronary thrombus in patients with acute
      coronary syndrome. In addition, OCT may enable identifying thin-cap
      fibroatheroma, the proliferation of vasa vasorum, and the distribution of
      macrophages surrounding vulnerable plaques. With its ability to view
      atherosclerotic lesions in vivo with such high resolution, OCT provides
      cardiologists with the tool they need to better understand the thrombosis-prone
      vulnerable plaques and acute coronary syndromes. This paper reviews the
      possibility of OCT for identification of vulnerable plaques in vivo.

PMID- 21941664
TI  - Presynaptic ionotropic receptors controlling and modulating the rules for spike
      timing-dependent plasticity.
AB  - Throughout life, activity-dependent changes in neuronal connection strength
      enable the brain to refine neural circuits and learn based on experience. In line
      with predictions made by Hebb, synapse strength can be modified depending on the
      millisecond timing of action potential firing (STDP). The sign of synaptic
      plasticity depends on the spike order of presynaptic and postsynaptic neurons.
      Ionotropic neurotransmitter receptors, such as NMDA receptors and nicotinic
      acetylcholine receptors, are intimately involved in setting the rules for
      synaptic strengthening and weakening. In addition, timing rules for STDP within
      synapses are not fixed. They can be altered by activation of ionotropic receptors
      located at, or close to, synapses. Here, we will highlight studies that uncovered
      how network actions control and modulate timing rules for STDP by activating
      presynaptic ionotropic receptors. Furthermore, we will discuss how interaction
      between different types of ionotropic receptors may create "timing" windows
      during which particular timing rules lead to synaptic changes.

PMID- 21941667
TI  - Optical coherence tomography analysis of attenuated plaques detected by
      intravascular ultrasound in patients with acute coronary syndromes.
AB  - Background. Recent intravascular ultrasound (IVUS) studies have demonstrated that
      hypoechoic plaque with deep ultrasound attenuation despite absence of bright
      calcium is common in acute coronary syndrome. Such "attenuated plaque" may be an
      IVUS characteristic of unstable lesion. Methods. We used optical coherence
      tomography (OCT) in 104 patients with unstable angina to compare lesion
      characteristics between IVUS-detected attenuated plaque and nonattenuated plaque.
      Results. IVUS-detected attenuated plaque was observed in 41 (39%) patients. OCT
      detected lipidic plaque (88% versus 49%, P < 0.001), thin-cap fibroatheroma (48%
      versus 16%, P < 0.001), plaque rupture (44% versus 11%, P < 0.001), and
      intracoronary thrombus (54% versus 17%, P < 0.001) were more often seen in IVUS
      detected attenuated plaques compared with nonattenuated plaques. Conclusions.
      IVUS-detected attenuated plaque has many characteristics of unstable coronary
      lesion. The presence of attended plaque might be an important marker of lesion
      instability.

PMID- 21941668
TI  - Atrioventricular dissociation after electroconvulsive therapy.
AB  - Electroconvulsive therapy (ECT) is increasingly used as a treatment for
      psychiatric disorders. Cardiac effects are the principal cause of medical
      complications in these patients. We report a case of atrioventricular (AV)
      dissociation that occurred after ECT that was treated with pacemaker
      implantation. The mechanisms contributing to the onset of AV dissociation in this
      patient, and the management and rationale for device therapy, in light of the
      most recent guidelines, are reviewed.

PMID- 21941670
TI  - Esophageal electrical cardioversion of atrial fibrillation: when esophagus gives
      a help to cardiologists.
AB  - Atrial fibrillation is a common clinical disease especially in the elderly and in
      patients with organic heart disease. Electrical cardioversion is the first choice
      therapeutic approach for patients in which sinus rhythm could improve the quality
      of life and where the maintenance of sinus rhythm is considered likely. There are
      different techniques to perform an electrical cardioversion, each with specific
      indications, advantages, and limitations. The method most frequently used to
      restore sinus rhythm is external direct current cardioversion; however, this
      technique has some disadvantages, since it requires a high energy and usually
      general anesthesia. Esophageal cardioversion is an alternative method to obtain
      restoration of sinus rhythm, warranting acute and long-term results absolutely
      comparable with those obtained by the conventional transthoracic technique,
      especially in obese and COPD patients with high thoracic impedance for whom the
      standard technique may be less effective.

PMID- 21941669
TI  - Organized atrial tachycardias after atrial fibrillation ablation.
AB  - The efficacy of catheter-based ablation techniques to treat atrial fibrillation
      is limited not only by recurrences of this arrhythmia but also, and not less
      importantly, by new-onset organized atrial tachycardias. The incidence of such
      tachycardias depends on the type and duration of the baseline atrial fibrillation
      and specially on the ablation technique which was used during the index
      procedure. It has been repeatedly reported that the more extensive the left
      atrial surface ablated, the higher the incidence of organized atrial
      tachycardias. The exact origin of the pathologic substrate of these trachycardias
      is not fully understood and may result from the interaction between preexistent
      regions with abnormal electrical properties and the new ones resultant from
      radiofrequency delivery. From a clinical point of view these atrial tachycardias
      tend to remit after a variable time but in some cases are responsible for
      significant symptoms. A precise knowledge of the most frequent types of these
      arrhythmias, of their mechanisms and components is necessary for a thorough
      electrophysiologic characterization if a new ablation procedure is required.

PMID- 21941671
TI  - Should We Monitor ScVO(2) in Critically Ill Patients?
AB  - Hemodynamic monitoring has become a real challenge in the intensive care unit. As
      an integrative parameter for oxygen supply/demand, venous oxygen saturation
      (SvO(2)) provided by pulmonary artery catheterization is one of the most popular
      parameters to assess the adequacy of cardiac output. However, technical
      limitations and potential iatrogenic complications constitute important limits
      for a widespread use. Regular central venous catheters coupled with a fiberoptic
      lumen for central venous oxygen saturation (ScvO(2)) monitoring have been
      proposed as a surrogate for SvO(2) monitoring. The purpose of the present article
      is to review the physiological backgrounds of circulation, the pathophysiology of
      circulatory failure and subsequent venous oxygen saturation alterations, and
      finally the merits and the limits of the use of ScvO(2) in different clinical
      situations.

PMID- 21941672
TI  - Assessing the sociocultural impacts of emerging molecular technologies for the
      early diagnosis of Alzheimer's disease.
AB  - Novel technologies for early diagnosis of Alzheimer's disease (AD) will impact
      the way society views and deals with AD and ageing. However, such "sociocultural"
      impacts are hardly acknowledged in standard approaches of technology assessment.
      In this paper, we outline three steps to assess such broader impacts. First,
      conceptual analysis of the ideas underlying technological developments shows how
      these technologies redraw the boundary between Alzheimer's disease and normal
      ageing and between biological and social approaches of ageing. Second,
      imaginative scenarios are designed depicting different possible futures of AD
      diagnosis and societal ways to deal with ageing and the aged. Third, such
      scenarios enable deliberation on the sociocultural impact of AD diagnostic
      technologies among a broad set of stakeholders. An early, broad, and democratic
      assessment of innovations in diagnostics of AD is a valuable addition to
      established forms of technology assessment.

PMID- 21941673
TI  - New thinking on the etiology and pathogenesis of late-onset Alzheimer's disease.

PMID- 21941674
TI  - Neanderthals versus Modern Humans: Evidence for Resource Competition from
      Isotopic Modelling.
AB  - During later MOIS3, in Europe two populations were present, autochthonous
      Neanderthals and modern humans. Ecological competition between these two
      populations has often been evoked but never demonstrated. Our aim is to establish
      whether resource competition occurred. In this paper, in order to examine the
      possibility of ecological competition between these two populations, 599 isotopic
      data were subjected to rigorous statistical treatment and analysis through mixing
      models. The aim of this paper was to compare dietary strategies of Neanderthals
      and modern humans over time. Our conclusions suggest that Neanderthals and modern
      humans shared dietary habits in the particular environmental context of MOIS3
      characterised in Europe by climatic deterioration. In this environmental context,
      the resource competition between Neanderthals and modern humans may have
      accelerated the disappearance of the Neanderthal population.

PMID- 21941676
TI  - Adiponectin in cardiovascular inflammation and obesity.
AB  - Inflammation is widely known to play a key role in the development and
      progression of cardiovascular diseases. It is becoming increasingly evident that
      obesity is linked to many proinflammatory and obesity-associated cardiovascular
      conditions (e.g., metabolic syndrome, acute coronary syndrome, and congestive
      heart failure). It has been observed that adipokines play an increasingly large
      role in systemic and local inflammation. Therefore, adipose tissue may have a
      more important role than previously thought in the pathogenesis of several
      disease types. This review explores the recently described role of adiponectin as
      an immunomodulatory factor and how it intersects with the inflammation associated
      with both cardiovascular and autoimmune pathologies.

PMID- 21941678
TI  - A systematic review of osteoporosis health beliefs in adult men and women.
AB  - Osteoporosis is major public health concern affecting millions of older adults
      worldwide. A systematic review was carried out to identify the most common
      osteoporosis health beliefs in adult men and women from descriptive and
      intervention studies. The Osteoporosis Health Belief Scale (OHBS) and
      Osteoporosis Self-efficacy Scale (OSES) evaluate osteoporosis health beliefs,
      including perceived susceptibility and seriousness, benefits, barriers, and self
      efficacy of calcium and exercise, and health motivation, and their relationship
      to preventive health behaviours. A comprehensive search of studies that included
      OHBS and OSES subscale scores as outcomes was performed. Fifty full-text articles
      for citations were reviewed based on inclusion criteria. Twenty-two articles met
      the inclusion criteria. Greater perceived seriousness, benefits, self-efficacy,
      health motivation, and fewer barriers were the most common health-belief
      subscales in men and women. Few studies were interventions (n = 6) and addressed
      osteoporosis health beliefs in men (n = 8). Taking health beliefs into
      consideration when planning and conducting education interventions may be useful
      in both research and practice for osteoporosis prevention and management;
      however, more research in this area is needed.

PMID- 21941679
TI  - Testosterone and the male skeleton: a dual mode of action.
AB  - Testosterone is an important hormone for both bone gain and maintenance in men.
      Hypogonadal men have accelerated bone turnover and increased fracture risk. In
      these men, administration of testosterone inhibits bone resorption and maintains
      bone mass. Testosterone, however, is converted into estradiol via aromatization
      in many tissues including male bone. The importance of estrogen receptor alpha
      activation as well of aromatization of androgens into estrogens was highlighted
      by a number of cases of men suffering from an inactivating mutation in the
      estrogen receptor alpha or in the aromatase enzyme. All these men typically had
      low bone mass, high bone turnover and open epiphyses. In line with these
      findings, cohort studies have confirmed that estradiol contributes to the
      maintenance of bone mass after reaching peak bone mass, with an association
      between estradiol and fractures in elderly men. Recent studies in knock-out mice
      have increased our understanding of the role of androgens and estrogens in
      different bone compartments. Estrogen receptor activation, but not androgen
      receptor activation, is involved in the regulation of male longitudinal
      appendicular skeletal growth in mice. Both the androgen and the estrogen receptor
      can independently mediate the cancellous bone-sparing effects of sex steroids in
      male mice. Selective KO studies of the androgen receptor in osteoblasts in male
      mice suggest that the osteoblast in the target cell for androgen receptor
      mediated maintenance of trabecular bone volume and coordination of bone matrix
      synthesis and mineralization. Taken together, both human and animal studies
      suggest that testosterone has a dual mode of action on different bone surfaces
      with involvement of both the androgen and estrogen receptor.

PMID- 21941677
TI  - Cellular Interplay between Cardiomyocytes and Nonmyocytes in Cardiac Remodeling.
AB  - Cardiac hypertrophy entails complex structural remodeling involving rearrangement
      of muscle fibers, interstitial fibrosis, accumulation of extracellular matrix,
      and angiogenesis. Many of the processes underlying cardiac remodeling have
      features in common with chronic inflammatory processes. During these processes,
      nonmyocytes, such as endothelial cells, fibroblasts, and immune cells, residing
      in or infiltrating into the myocardial interstitium play active roles. This paper
      mainly addresses the functional roles of nonmyocytes during cardiac remodeling.
      In particular, we focus on the communication between cardiomyocytes and
      nonmyocytes through direct cell-cell interactions and autocrine/paracrine
      mediated pathways.

PMID- 21941680
TI  - Fracture Incidence, Quality of Life, and Back Pain during 18-Months Treatment
      with Teriparatide in Greek Postmenopausal Women with Osteoporosis: Results from
      the European Forsteo Observational Study.
AB  - Objective. To evaluate fracture incidence, effects on health-related quality of
      life(QoL), back pain (BP) occurrence and treatment compliance in Greek post
      menopausal osteoporotic women treated with teriparatide (TPTD) for up to 18
      months, in a naturalistic setting. Methods. 301 patients provided baseline
      information on demographic characteristics, fracture history, osteoporosis
      related medication and risk factors. During treatment, QoL and BP severity were
      evaluated. Results. Mean (SD) age was 69.5 (+/-8.5) years. Fracture history was
      reported by 92.5% of patients. Incidence of fractures (per 10,000 patients/years)
      ranged from 402 during 0-6 months of treatment, to 346 during 12-18 months. All 5
      dimensions of QoL showed improvement. At baseline and 18 months, BP was reported
      by 93.2% and 64.2% of patients, respectively. BP and limitation of activities
      were quantified as moderate or severe by 89.9% and 62.3% of patients at baseline
      versus 32.4% and 14.8% at 18 months. Patients on treatment at 6, 12, 17, and 18
      months were 92.6%, 88.3%, 79.6%, and 36.5%, respectively. Conclusions. In the
      Greek EFOS study cohort, patients prescribed TPTD were severely osteoporotic,
      with considerable health-related problems. Significant improvements in QoL and BP
      together with low fracture rates and high compliance have been recorded during
      treatment.

PMID- 21941681
TI  - Why can insulin resistance be a natural consequence of thyroid dysfunction?
AB  - Evidence for a relationship between T4 and T3 and glucose metabolism appeared
      over 100 years ago when the influence of thyroid hormone excess in the
      deterioration of glucose metabolism was first noticed. Since then, it has been
      known that hyperthyroidism is associated with insulin resistance. More recently,
      hypothyroidism has also been linked to decreased insulin sensitivity. The
      explanation to this apparent paradox may lie in the differential effects of
      thyroid hormones at the liver and peripheral tissues level. The purpose of this
      paper is to explore the effects of thyroid hormones in glucose metabolism and
      analyze the mechanisms whereby alterations of thyroid hormones lead to insulin
      resistance.

PMID- 21941682
TI  - Myxedema coma: a new look into an old crisis.
AB  - Myxedema crisis is a severe life threatening form of decompensated hypothyroidism
      which is associated with a high mortality rate. Infections and discontinuation of
      thyroid supplements are the major precipitating factors while hypothermia may not
      play a major role in tropical countries. Low intracellular T3 leads to
      cardiogenic shock, respiratory depression, hypothermia and coma. Patients are
      identified on the basis of a low index of suspicion with a careful history and
      examination focused on features of hypothyroidism and precipitating factors.
      Arrythmias and coagulation disorders are increasingly being identified in
      myxedema crisis. Thyroid replacement should be initiated as early as possible
      with careful attention to hypotension, fluid replacement and steroid replacement
      in an intensive care facility. Studies have shown that replacement of thyroid
      hormone through ryles tube with a loading dose and maintenance therapy is as
      efficacious as intravenous therapy. In many countries T3 is not available and
      oral therapy with T4 can be used effectively without major significant difference
      in outcomes. Hypotension, bradycardia at presentation, need for mechanical
      ventilation, hypothermia unresponsive to treatment, sepsis, intake of sedative
      drugs, lower GCS and high APACHE II scores and Sequential Organ Failure
      Assessment (SOFA) scores more than 6 are significant predictors of mortality in
      myxedema crisis. Early intervention in hypothyroid patients developing sepsis and
      other precipitating factors and ensuring continued intake of thyroid supplements
      may prevent mortality and morbidity associated with myxedema crisis.

PMID- 21941683
TI  - Biological behavior of papillary carcinoma of the thyroid including squamous cell
      carcinoma components and prognosis of patients who underwent locally curative
      surgery.
AB  - Thyroid carcinoma showing squamous differentiation throughout the entire lesion
      is diagnosed as squamous cell carcinoma of the thyroid (SCCT) in the WHO
      classification. This entity is a rare disease and shows a dire prognosis;
      however, squamous differentiation is more frequently detected in only a portion
      of papillary thyroid carcinoma. In this paper, we present our experience of 10
      patients (8 primary lesions and 2 with recurrence in the lymph nodes) with
      papillary thyroid carcinoma having an SCC component (PTC-SCC). Only 3 of 8
      primary lesions (38%) and none of the 2 recurrent nodes were preoperatively
      diagnosed as or suspected of having SCC components. All 10 patients underwent
      locally curative surgery. To date, 3 patients have died of carcinoma, and 2 had
      distant metastasis at diagnosis or had an undifferentiated carcinoma component.
      The other 7 are currently alive 5 to 43 months after diagnosis. Systemic adjuvant
      therapy after the detection of recurrence was effective for 2 patients. It is
      possible that some PTC-SCC patients without distant metastasis who undergo
      locally curative surgery can survive for a prolonged period and adjuvant
      therapies can be effective for local and distant recurrences.

PMID- 21941675
TI  - Tissue factor, blood coagulation, and beyond: an overview.
AB  - Emerging evidence shows a broad spectrum of biological functions of tissue factor
      (TF). TF classical role in initiating the extrinsic blood coagulation and its
      direct thrombotic action in close relation to cardiovascular risks have long been
      established. TF overexpression/hypercoagulability often observed in many clinical
      conditions certainly expands its role in proinflammation, diabetes, obesity,
      cardiovascular diseases, angiogenesis, tumor metastasis, wound repairs, embryonic
      development, cell adhesion/migration, innate immunity, infection, pregnancy loss,
      and many others. This paper broadly covers seminal observations to discuss TF
      pathogenic roles in relation to diverse disease development or manifestation.
      Biochemically, extracellular TF signaling interfaced through protease-activated
      receptors (PARs) elicits cellular activation and inflammatory responses. TF
      diverse biological roles are associated with either coagulation-dependent or
      noncoagulation-mediated actions. Apparently, TF hypercoagulability refuels a
      coagulation-inflammation-thrombosis circuit in "autocrine" or "paracrine"
      fashions, which triggers a wide spectrum of pathophysiology. Accordingly, TF
      suppression, anticoagulation, PAR blockade, or general anti-inflammation offers
      an array of therapeutical benefits for easing diverse pathological conditions.

PMID- 21941684
TI  - Nondipping in Parkinson's disease.
AB  - Objective. The aim of this study was to identify patients with Parkinson's
      disease who showed loss or decrease of nocturnal blood pressure fall (nondipper
      patients) as a marker of autonomic dysfunction. Presence or absence of
      orthostatic hypotension was considered to investigate whether alterations in
      circadian blood pressure pattern are associated with posture-related
      dysregulation of blood pressure. Methods. 40 patients with Parkinson's disease
      underwent 24-hour blood pressure monitoring. 21 patients were diagnosed with
      arterial hypertension and received anti-hypertensive drugs. Nondipper patients
      were defined as having nocturnal decrease of mean systolic and diastolic blood
      pressure less than 10%. Presence or absence of orthostatic hypotension was
      determined by Schellong's test. Results. We identified 35 nondipper patients
      (88%). Nondipping was detected in 20 patients with orthostatic hypotension (95%)
      and in 15 patients without orthostatic hypotension (79%). 18 patients with
      hypertensive and 22 patients with normal blood pressure values were detected.
      Conclusions. In conclusion 24-hour blood pressure monitoring showed a high
      prevalence of nondipping in 40 patients with Parkinson's disease with and without
      orthostatic hypotension independent of coexisting arterial hypertension and
      antihypertensive treatment. 24-hour blood pressure monitoring may be useful to
      identify non-dipping as a marker of autonomic dysfunction in patients with
      Parkinson's disease.

PMID- 21941685
TI  - A Manipulation of Visual Feedback during Gait Training in Parkinson's Disease.
AB  - Visual cues are known to improve gait in Parkinson's disease (PD); however, the
      contribution of optic flow continues to be disputed. This study manipulated
      transverse line cues during two gait training interventions (6 weeks). PD
      subjects (N = 42) were assigned to one of three groups: treadmill (TG),
      overground (OG), or control group (CG). Participants walked across lines placed
      on either treadmills or 16-meter carpets, respectively. The treadmill (TG)
      offered a reduced dynamic flow from the environment, while lines presented on the
      ground (OG) emphasized optic flow related to the participant's own displacement.
      Both interventions significantly improved (and maintained through retention
      period) step length, thus improving walking velocity. Only the OG improved in the
      TUG test, while only the TG showed hints of improving (and maintaining) motor
      symptoms. Since gait improvements were found in both training groups, we conclude
      that by reducing optic flow, gait benefits associated with visual cueing training
      can still be achieved.

PMID- 21941686
TI  - Walking ability is a major contributor to fear of falling in people with
      Parkinson's disease: implications for rehabilitation.
AB  - Although fear of falling (FOF) is common in people with Parkinson's disease (PD),
      there is a lack of research investigating potential predictors of FOF. This study
      explored the impact of motor, nonmotor, and demographic factors as well as
      complications of drug therapy on FOF among people with PD. Postal survey data
      (including the Falls Efficacy Scale, FES) from 154 nondemented people with PD
      were analyzed using multiple regression analyses. Five significant independent
      variables were identified explaining 74% of the variance in FES scores. The
      strongest contributing factor to FOF was walking difficulties (explaining 68%),
      followed by fatigue, turning hesitations, need for help in daily activities, and
      motor fluctuations. Exploring specific aspects of walking identified three
      significant variables explaining 59% of FOF: balance problems, limited ability to
      climb stairs, and turning hesitations. These results have implications for
      rehabilitation clinicians and suggest that walking ability is the primary target
      in order to reduce FOF. Specifically, balance, climbing stairs, and turning seem
      to be of particular importance.

PMID- 21941688
TI  - Effects of FK506 on Hippocampal CA1 Cells Following Transient Global
      Ischemia/Reperfusion in Wistar Rat.
AB  - Transient global cerebral ischemia causes loss of pyramidal cells in CA1 region
      of hippocampus. In this study, we investigated the neurotrophic effect of the
      immunosuppressant agent FK506 in rat after global cerebral ischemia. Both common
      carotid arteries were occluded for 20 minutes followed by reperfusion. In
      experimental group 1, FK506 (6 mg/kg) was given as a single dose exactly at the
      time of reperfusion. In the second group, FK506 was administered at the beginning
      of reperfusion, followed by its administration intraperitoneally (IP) 6, 24, 48,
      and 72 hours after reperfusion. FK506 failed to show neurotrophic effects on CA1
      region when applied as a single dose of 6 mg/kg. The cell number and size of the
      CA1 pyramidal cells were increased, also the number of cell death decreased in
      this region when FK506 was administrated 48 h after reperfusion. This work
      supports the possible use of FK506 in treatment of ischemic brain damage.

PMID- 21941687
TI  - Human polyomaviruses in skin diseases.
AB  - Polyomaviruses are a family of small, nonenveloped viruses with a circular double
      stranded DNA genome of ~5,000 base pairs protected by an icosahedral protein
      structure. So far, members of this family have been identified in birds and
      mammals. Until 2006, BK virus (BKV), JC virus (JCV), and simian virus 40 (SV40)
      were the only polyomaviruses known to circulate in the human population. Their
      occurrence in individuals was mainly confirmed by PCR and the presence of virus
      specific antibodies. Using the same methods, lymphotropic polyomavirus,
      originally isolated in monkeys, was recently shown to be present in healthy
      individuals although with much lower incidence than BKV, JCV, and SV40. The use
      of advanced high-throughput sequencing and improved rolling circle amplification
      techniques have identified the novel human polyomaviruses KI, WU, Merkel cell
      polyomavirus, HPyV6, HPyV7, trichodysplasia spinulosa-associated polyomavirus,
      and HPyV9. The skin tropism of human polyomaviruses and their dermatopathologic
      potentials are the focus of this paper.

PMID- 21941689
TI  - Physical activity, ambulation, and motor impairment late after stroke.
AB  - Objective. To assess walking capacity and physical activity using clinical
      measures and to explore their relationships with motor impairment late after
      stroke. Subjects. A nonrandomised sample of 22 men and 9 women with a mean age of
      60 years, 7-10 years after stroke. Methods. Fugl-Meyer Assessment, maximum
      walking speed, 6 min walk test, perceived exertion, and heart rate were measured,
      and the Physiological Cost Index was calculated. Physical activity was reported
      using The Physical Activity Scale for the Elderly. Results. Mean (SD) 6 min
      walking distance was 352 (+/-136) m, and Physiological Cost Index was 0.60 (+/
      0.41). Self-reported physical activity was 70% of the reference. Motor impairment
      correlated with walking capacity but not with the physical activity level.
      Conclusion. It may be essential to enhance physical activity even late after
      stroke since in fairly young subjects both walking capacity and the physical
      activity level were lower than the reference.

PMID- 21941690
TI  - Determination of testicular blood flow in camelids using vascular casting and
      color pulsed-wave Doppler ultrasonography.
AB  - We describe the vasculature of the camelid testis using plastic casting. We also
      use color pulsed-wave Doppler ultrasonography to measure testicular blood flow
      and compare the differences between testicular blood flow in fertile and
      infertile camelids. The testicular artery originates from the ventral surface of
      the aorta, gives rise to an epididymal branch, and becomes very tortuous as it
      approaches the testis. Within the supratesticular arteries, peak systolic
      velocity (PSV) was higher in fertile males compared to infertile males (P =
      0.0004). In addition, end diastolic velocity (EDV) within the supratesticular
      arteries was higher for fertile males when compared to infertile males (P =
      0.0325). Within the marginal arteries, PSV was also higher in fertile males
      compared to infertile males (P = 0.0104). However, EDV within the marginal
      arteries was not significantly different between fertile and infertile males (P =
      0.121). In addition, the resistance index was not significantly different between
      fertile and infertile males within the supratesticular (P = 0.486) and marginal
      arteries (P = 0.144). The significance of this research is that in addition to
      information obtained from a complete reproductive evaluation, a male camelid's
      fertility can be determined using testicular blood flow measured by Doppler
      ultrasonography.

PMID- 21941691
TI  - War rape, natality and genocide.
AB  - Feminist philosophy can make an important contribution to the field of genocide
      studies, and issues relating to gender and war are gaining new attention. In this
      article I trace legal and philosophical analyses of sexual violence against women
      in war. I analyze the strengths and limitations of the concept of social death
      introduced into this field by Claudia Card-for understanding the genocidal
      features of war rape, and draw on the work of Hannah Arendt to understand the
      central harm of genocide as an assault on natality. The threat to natality posed
      by the harms of rape, forced pregnancy and forced maternity lie in the potential
      expulsion from the public world of certain groups-including women who are
      victims, members of the 'enemy' group, and children born of forced birth.

PMID- 21941692
TI  - Assuming too much? Participatory water resource governance in South Africa.
AB  - This paper argues that participation in natural resource management, which is
      often coupled with moves for more local ownership of decision making, is based on
      three sets of assumptions: about the role of the state, the universality of
      application of such approaches and the transformatory potential of institutional
      reform. The validity of these assumptions requires investigation in view of the
      rapid institutionalisation and scaling-up of participatory approaches,
      particularly in developing country contexts. Post-apartheid South Africa is
      widely recognised as a pioneer of participatory and devolutionary approaches,
      particularly in the field of water resources. It is 12 years since the
      promulgation of the forward-thinking 1998 National Water Act, and thus an
      opportune moment to reflect on South Africa's experiences of participatory
      governance. Drawing on empirical research covering the establishment of the first
      Catchment Management Agency, and the transformation of existing Irrigation Boards
      into more inclusive Water User Associations in the Inkomati Water Management
      Area, it emerges that there may be fundamental weaknesses in the participatory
      model and underlying assumptions, and indeed such approaches may actually
      reinforce inequitable outcomes: the legacy of long-established institutional
      frameworks and powerful actors therein continues to exert influence in post
      apartheid South Africa, and has the potential to subvert the democratic and
      redistributive potential of the water reforms. It is argued that a reassessment
      of the role of the state is necessary: where there is extreme heterogeneity in
      challenging catchments more, rather than less, state intervention may be required
      to uphold the interests of marginalised groups and effect redistribution.

PMID- 21941693
TI  - Market empowerment of the patient: the French experience.
AB  - Through analysis of the French experience, this article explores the way economic
      policy has sought to encourage active, well-informed patients by giving them
      market power. The new status of the patient as consumer is based on two
      foundations: the endeavour to build a healthcare market and the activation of
      demand-based policies. The keystone of this new system is a conception of the
      market as a process constructed by economic policy. Recent measures such as the
      standardization of care and the introduction of incentives to respect a treatment
      pathway then constitute effective levers to establish a free-market rationale.

PMID- 21941694
TI  - J. M. Despreaux' lichens from the Canary Islands and West Africa: an account of a
      19th century collection found in an English archive.
AB  - This is an historical and descriptive account of 28 herbarium specimens, 27
      lichens and an alga, found in the archives of Charles Chalcraft, a descendant of
      the Bedford family, who were dye manufacturers in Leeds, England, in the 19th
      century. The lichens comprise 13 different morphotypes collected in the Canary
      Islands and West Africa by the French botanist J. M. Despreaux between 1833 and
      1839. The collections include samples of "Roccella fuciformis", "R. phycopsis"
      and "R. tinctoria" (including the fertile morphotype "R. canariensis"), "Ramalina
      crispatula" and "R. cupularis", two distinct morphotypes of "Sticta", "S.
      canariensis" and "S. dufouri", "Physconia enteroxantha", "Pseudevernia furfuracea
      var. ceratea" and "Pseudocyphellaria argyracea". The herbarium also includes
      authentic material of "Parmotrema tinctorum" and a probable syntype of
      "Seirophora scorigena". Most of these species are known as a source of the purple
      dye orchil, which was used to dye silk and wool.

PMID- 21941695
TI  - Rapid method for the isolation of the mature collagen cross-links,
      hydroxylysylpyridinoline and lysylpyridinoline.
AB  - Hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) are two non-reducible
      cross-links of mature collagen which are formed by a sequence of post
      translational modifications. HP is a derivative of three residues of
      hydroxylysine and is present in almost all mature tissues (e.g., tendons, vessel
      walls, cartilage, teeth and bone). LP is a derivative of two residues of
      hydroxylysine and one residue of lysine and is present only in dentine and bone.
      Neither cross-link is found in normal human skin. HP and LP were purified from
      commercially available bone gelatine ("ossein hydrolysate") by preparative
      reversed-phase HPLC and the degree of purity was verified by amino acid
      determination ( > 98% dry mass). Hydroxylysylpyridinoline and lysylpyridinoline
      are promising markers in urine of collagen resorption because their levels in
      urine should reflect only the breakdown of collagen fibres of skeletal tissues.
      The two components were used as external standards and the determination of HP
      and LP in urine provides a good means for the specific evaluation of pathological
      conditions associated with increased bone resorption, e.g., high turnover post
      menopausal osteoporosis.

PMID- 21941696
TI  - [Chemistry as a technology of the future: the coal-tar dye industry before World
      War I].

PMID- 21941697
TI  - Ethnic conflict in China: characteristics, causes, and countermeasures.

PMID- 21941698
TI  - Harmful silica fibres and slave demography.

PMID- 21941699
TI  - Reforming China's state socialist workfare system: a cautionary and incremental
      approach.

PMID- 21941700
TI  - Representation, structure and agency: Divorce in the French Soudan    during the
      early twentieth century.

PMID- 21941701
TI  - [Russian policies and Muslim identity: the Volga-Ural territory in the 19th
      century].

PMID- 21941702
TI  - [Role of diagnostic imaging in early diagnosis and stage determination of
      rheumatoid arthritis].

PMID- 21941703
TI  - Reflecting on laughing matters.

PMID- 21941704
TI  - Professionals online: sharing too much?

PMID- 21941705
TI  - Staying alive.

PMID- 21941706
TI  - A qualitative exploration of first-time fathers' experiences of becoming a
      father.
AB  - This study aimed to explore first-time fathers' experiences of becoming a father,
      focusing on their expectations, experiences, and how they are coping with this
      transition. An interpretative phenomenological analysis (IPA) epistemology and
      methodology were adopted as the study was focused on understanding the meaning
      and experiences of this transition for fathers. Nine participants were recruited
      from seven NCT antenatal classes. The mean age of participants was 38 years
      (range=30 to 46 years). Participants completed a semi-structured interview
      between four and eleven weeks post birth. One overarching superordinate theme was
      derived: 'searching for a place'. This theme consisted of three sub-themes--'the
      separation connection struggle', 'a sense of utility, agency and control' and
      'changing focus of affection'. The findings expand on our understanding of new
      fathers' experiences, and suggest that first-time fathers experienced an array of
      psychological responses during each stage of their transition as they searched
      for their place as father in relation to their partner, child and work.
      Professionals working in antenatal and postnatal services should discuss with men
      the possible emotional and psychological changes they may go through to enable
      more realistic expectations to be considered.

PMID- 21941707
TI  - Health visitor views on consultation using the Solihull approach: a grounded
      theory study.
AB  - Consultation is integral to maintaining competence for health professionals and
      involves a collaborative relationship between specialist and primary care
      services. Although consultation aims to support them in their work, existing
      literature exploring health visitors' experiences of consultation is limited.
      This study explored health visitors' experiences of consultation in relation to
      their clinical practice, their experience of their work and its impact on the
      wider service. In all, 10 health visitors were interviewed using a semi
      structured guide and analysis was subjected to a grounded theory framework.
      Participants' views were influenced by a combination of factors--consultants'
      training specific to their role, their communication and engagement,
      consultation's support of joint-working and/or transitions, and its relevance to
      and impact upon practice. Findings suggest that such interface activities require
      effective co-ordination, communication and structuring strategies, highlighting
      the importance of future initiatives in developing health visitors' mental health
      role further. Given the comparative lack of evaluation of such activities, these
      findings may inform policy-making and service development to ensure high quality
      of service delivery.

PMID- 21941708
TI  - Reducing burnout and stress: the effectiveness of clinical supervision.
AB  - Health visitors and school nurses have been identified as a particularly
      vulnerable group to stress given the complex, frontline clinical work that they
      are involved in. Recent high-profile reviews of safeguarding practices have
      brought an increased pressure on the profession. This paper provides evidence of
      the effectiveness of a model of clinical supervision that reduced burnout and
      stress for health visitor and school nurse Leaders. Commissioned by NHS West
      Midlands, the project delivered supervision to health visitors and school nurses
      with a safeguarding leadership responsibility within their organisation.

PMID- 21941709
TI  - Autism spectrum disorders in childhood: a clinical update.
AB  - Autism spectrum disorders refer to a range of conditions such as autism disorder
      and Asperger syndrome that may affect about 1% of children in the UK. This paper
      aims to consider diagnosis and to provide an overview of potentially useful
      therapies and support.

PMID- 21941710
TI  - The value of being recognised.

PMID- 21941711
TI  - Publishing from work.

PMID- 21941712
TI  - What's wrong with the Bill.

PMID- 21941713
TI  - 100,000 fewer nurses in 10 years predicted.

PMID- 21941714
TI  - CNO roles to attract high flyers.

PMID- 21941715
TI  - "Nurses will be at the forefront of designing health services".

PMID- 21941716
TI  - "Having a smoke with your client used to feel like good nursing".

PMID- 21941717
TI  - "A half-empty glass does not prove your patient can drink".

PMID- 21941718
TI  - Measuring and managing fluid balance.
AB  - Ensuring patients are adequately hydrated is an essential part of nursing care,
      yet a recent report from the Care Quality Commission found "appalling" levels of
      care in some NHS hospitals, with health professionals failing to manage
      dehydration. This article discusses the importance of hydration, and the health
      implications of dehydration and overhydration. It also provides an overview of
      fluid balance, including how and why it should be measured, and discusses the
      importance of accurate fluid balance measurements.

PMID- 21941719
TI  - What is the evidence for drinking eight cups of fluid a day?

PMID- 21941720
TI  - Ensuring hydration.

PMID- 21941721
TI  - Using red jugs to improve hydration.

PMID- 21941722
TI  - ECGs 2: analysis of a rhythm strip.

PMID- 21941723
TI  - Myth buster.

PMID- 21941724
TI  - "Log on to social media to reach service users".

PMID- 21941725
TI  - Online rules breached.

PMID- 21941726
TI  - "We are still pushing for more movement on the health bill".

PMID- 21941727
TI  - "Forget nudging, the public health strategy doesn't work".

PMID- 21941728
TI  - "We can consign this nasty infection to the history books".

PMID- 21941729
TI  - Driving down catheter associated infection rates.
AB  - Caring for patients with an indwelling urinary catheter is common in nursing
      practice. While catheters are essential for some patients, evidence suggests that
      in many cases catheterisation may be unjustified. This exposes patients to
      significant and unnecessary risks of acquiring urinary tract infections,
      extending their length of stay and imposing an extra burden of care and cost on
      healthcare providers. Improving care for patients with catheters depends on good
      education, robust research and audit pathways, evidenced best practice, adequate
      resources, and effective devices and treatment. This article discusses national
      and local initiatives that have been developed to enable health professionals to
      drive down catheter-associated urinary tract infections rates.

PMID- 21941730
TI  - Can silver alloy catheters reduce infection rates?
AB  - BACKGROUND: Catheter associated urinary tract infections remain a persistent
      challenge in healthcare practice. AIM: To establish whether silver alloy urinary
      catheters reduce catheter-associated urinary tract infections compared with
      standard silicone or latex urinary catheters in short-term hospitalised adult
      patients. METHOD: Analysis of eight studies using the Critical Appraisal Skills
      for Practitioners tool. RESULTS: A consistent pattern emerged that supported the
      effectiveness of silver alloy urinary catheters over uncoated catheters to reduce
      infections in adult patients. CONCLUSION: Changing practice to use silver alloy
      catheters would have a significant impact on patient care.

PMID- 21941731
TI  - Urinary catheter use in end of life care.
AB  - Patients nearing the end of life can become agitated by a full bladder and may
      need urgent urinary catheterisation. However, urethral catheterisation needs
      authorisation by a doctor. Nurses at a London trust developed a urinary
      catheterisation consent form permitting nurses to perform this procedure when it
      becomes necessary without having to gain medical authorisation. This article
      discusses how the consent form can help improve bladder management, ensuring
      terminally ill patients do not have to attend the emergency department to be
      catheterised.

PMID- 21941732
TI  - ECGs 3: identifying cardiac rhythms.

PMID- 21941733
TI  - Critical mass.

PMID- 21941734
TI  - [Effects of forest gap on tree species regeneration and diversity of mixed
      broadleaved Korean pine forest in Xiaoxing'an Mountains].
AB  - This paper studied the quantitative characteristics of main tree species along a
      forest gap gradient (gap center-near gap center-gap border) of mixed broadleaved
      Korean pine forest in Xiaoxing'an Mountains, as well as the effects of forest gap
      size on the regeneration of the tree species. In forest gap, the density of shrub
      species was obviously larger than that in non-gap, and the density ratio of the
      same shrub species in forest gap to in non-gap ranged from 1.08 to 18.15. With
      the increase of gap size, the regeneration density of tree seedlings increased,
      and that of sapling I (H > or = 1 m, DBH < or = 2 cm) and sapling II (H > or = 1
      m, 2 cm < DBH < or = 5 cm) exhibited multiple peak curve. The overall
      regeneration density of shrubs in forest gaps varied mainly with the amounts of
      tree seedlings and sapling I. The mean height, mean basal diameter, species
      density, and individual density of trees in different locations of forest gaps
      were all different. From gap center to non-gap, the importance value of tree
      species seedlings in regeneration layer was ranked in gap center > near gap
      center > gap border > non-gap, the tree species evenness presented a variation of
      high-low-high, and the species diversity decreased in the order of early phase
      gap > mid phase gap > late phase gap.

PMID- 21941735
TI  - [Leaf litter decomposition and nutrient release of different stand types in a
      shelter belt in Xinjiang arid area].
AB  - From October 2007 to November 2008, an in situ mesh bag experiment was conducted
      to study the leaf litter decomposition and nutrient release of forest stands
      Populus alba var. pyramidalis, Amorpha fruticosa, and P. alba var. pyramidalis +
      A. fruticosa in a shelter belt in Karamay, Xinjiang. It was observed that the
      mass loss rate of leaf litter differed with tree species, and was significantly
      affected by leaf litter composition. The leaf litter of P. alba var. pyramidalis
      + A. fruticosa was more easily decomposed than that of the other two mono
      dominance forest trees. The analysis with improved Olson' s exponential model
      indicated that P. alba var. pyramidalis leaf litter had the lowest decomposition
      coefficient (k = 0.167), while P. alba var. pyramidalis + A. fruticosa leaf
      litter had the highest one (k = 0.275). According to the model, it would cost for
      about 2.41-4.19 years and 10.79-17.98 years to have 50% and 95% decomposition of
      the three kind leaf litters, respectively. The residual rates of nitrogen,
      phosphorus, and potassium in the three kind leaf litters differed with
      decomposition period. After one year decomposition, potassium was wholly
      released, while nitrogen and phosphorus were immobilized or enriched via the
      absorption from surrounding environment. Except that the A. fruticosa leaf litter
      had a decreased organic carbon decomposition rate in the mid period of
      decomposition, the leaf litters of P. alba var. pyramidalis and P. alba var.
      pyramidalis + A. fruticosa all had an increasing organic carbon decomposition
      rate with the decomposition, which was about 35.5%-44.2% after one year
      decomposition. The C/N value of the leaf litters had a decreasing trend, and the
      decrement was smaller in the early and mid periods but larger in the late period
      of decomposition.

PMID- 21941736
TI  - [Photosynthetic parameters and chlorophyll fluorescence characteristics of
      Pleioblastus kongosanensis f. aureostriaus under drought stress].
AB  - A pot experiment was conducted to study the variations of Pleioblastus
      kongosanensis f. aureostriaus plant morphology, leaf water content (LWC) , leaf
      water potential (LWP) , photosynthetic parameters, chlorophyll fluorescence
      parameters, and soil water content (SWC) under natural drought stress, as well as
      the relationships between these variations and environmental factors. On the 17th
      day under the stress, the P. kongosanensis presented damaged symptom. Its leaves
      dehydrated, drooped, and wrap-formed. On the 43rd day, the aboveground part of
      the plant died from dehydration. When the plant was re-watered for 10 days, the
      chlorophyll fluorescence parameters had no significant differences with those on
      the 43rd day under the stress. The SWC decreased significantly in 0-21 d of the
      stress, and the LWP and LWC dropped rapidly and significantly after 17 d and 29
      d, respectively. With the increase of drought stress, the leaf transpiration rate
      (Tr) and stomatal conductance (g(s)) had a persistent decline, photosynthetic
      rate (Pn) had a greater fluctuation, and instantaneous water use efficiency
      (PWUE) decreased after an initial increase. After 17 d drought stress, the
      limiting factor of Pn was from stomatal to non-stomatal, and the actual
      photosynthetic efficiency (phiPS II) declined significantly; after 25 d, the
      photosynthetic organ was damaged, and the maximum photochemical efficiency of PS
      II (Fv/Fm) and non-photochemical quenching (qN) changed significantly from 0.64
      to -0.11 and from 0.79 to 0.33, respectively. The Tr, g(s), and PWUE had close
      correlations with LWP; the Pn, Tr, and g(s) were sensitive to air relative
      humidity (RH); and the gs was the main factor causing the diurnal variations of
      photosynthetic parameters. It was suggested that P. kongosanensis could grow well
      on the soil with relative moisture content > or = 12% and drought duration less
      than 25 d.

PMID- 21941737
TI  - [Effects of domestic wastewater slow infiltration on the growth of poplar
      'Zhonglin 2001' plantation].
AB  - A slow infiltration experiment with different hydraulic loads (0, 3, 6, 9, 12,
      and 15 cm per week) of domestic wastewater was conducted in a 'Zhonglin 2001'
      poplar plantation to study the effects of the wastewater slow infiltration on the
      growth of the plantation. Comparing with the control (0 cm), the other five
      treatments increased the soil organic matter, total N, total P, total K, and Na+
      contents in the plantation averagely by 1.940 g x kg(-1), 0.115 g x kg(-1), 0.029
      g x kg(-1), 1.454 g x kg(-1) and 0.030 g x kg(-1), respectively. At lower
      hydraulic loads (3-12 cm per week), the poplar biomass growth and the N, P and
      Na+ contents in different poplar organs averagely increased by 17.583 t x hm(-2)
      x a(-1), 3.086 g x kg(-1), 0.645 g x kg(-1), and 0.121 g x kg(-1), with the
      maximum (36.252 t x hm(-2) x a(-1), 13.162 g x kg(-1), 5.137 g x kg(-1), and
      0.361 g x kg(-1), respectively) at hydraulic loads 6-12 cm per week. The further
      increase of the hydraulic load decreased the poplar biomass growth and the N, P
      and Na+ contents in different poplar organs. The K content in different poplar
      organs decreased with increasing hydraulic load. Treating with domestic
      wastewater increased the leaf length, decreased the leaf asymmetry, and delayed
      leaf-falling. At high hydraulic load (15 cm per week), the higher soil Na+ and
      water contents would threat the poplar growth. The proper domestic wastewater
      hydraulic loads for the growth of poplar 'Zhonglin 2001' plantation would be 3-12
      cm per week.

PMID- 21941738
TI  - [Photosynthetic mechanisms of northern boundary formation of Quercus wutaishanica
      forest in Loess Plateau of northern Shaanxi Province].
AB  - Aimed to understand the causes of the boundary formation of Quercus wutaishanica
      forest, four sites were chosen along a precipitation and thermal gradient from
      Qinling Mountain to Loess Plateau of northern Shaanxi Province, i. e. , north
      slope of Qinling Mountain (Jiwozi) and southern (Chenjiashan), central
      (Huaishuzhuang), and northern site (Xiasiwan) of Loess Plateau, with the gas
      exchange, chlorophyll fluorescence parameters, stomatal density, and stomatal
      size of Q. wutaishanica leaves measured. From the south to the north along the
      precipitation and thermal gradient, weather varied from cool and humid to warm
      and semi-arid, and the maximum net photosynthetic rate (Pn max) and light
      saturation point (Lsp) of Q. wutaishanica leaves reduced obviously from 13.34 to
      6.99 micromol CO2 x m(-2) x s(-1) and from 1489.9 to 1055.6 micromol x m(-2) x s(
      1), dark respiration rate (Rd) and light compensation point (Lcp) increased
      evidently from 0.313 to 1.080 micromol CO2 x m(-2) x s(-1) and from 7.49 to 31.96
      micromol x m(-2) x s(-1), the minimum fluorescence (F0) and coefficient of non
      photochemical quenching (NPQ) displayed an increasing trend, and actual
      photochemical quantum yield of PS II (phiPS II), apparent electron transport
      rates (ETR), and coefficient of photochemical quenching (qP) reduced obviously.
      These results demonstrated that the photosynthetic capacity of Q. wutaishanica
      declined gradually with decreasing precipitation, but the stomatal density and
      stomatal size showed no obvious difference among the study sites except for the
      southern site of Loess Plateau. It was speculated that the depressed net
      photosynthetic rate of Q. wutaishanica leaves induced by the declined Phi PS II
      and ETR Could be one of the main causes for the formation of northern boundary of
      Q. wutaishanica forest.

PMID- 21941739
TI  - [Soil quality assessment of alpine meadow in Haibei State of Qinghai Province].
AB  - Taking the typical alpine meadows Potentilla froticosa shrub meadow, Kobresia
      humilis meadow, and K. pygmaea meadow in the Haibei State of Qinghai Province as
      the research objects, a comprehensive assessment of soil quality was conducted by
      principal component analysis (PCA), with seven indices of soil microbial
      activities and ten indices of soil chemical properties. The soil quality of the
      alpine meadow could be characterized by three principal components (PC). In the
      first component (PC1), 13 indices had high factorial loads; in the second
      component (PC2), 3 indices had high factorial loads; in the third component
      (PC3), only one index, total phosphors, had high factorial load. In combining
      with Norm values, eleven indices including microbial biomass carbon (MBC),
      urease, alkaline phosphatase, protease, organic matter, total N, available N,
      available P, available K, bulk density, and CEC were selected to establish
      minimum data set (MDS) for the comprehensive assessment of soil quality of alpine
      meadow in Haibei. The PCA and corresponding weight coefficient analysis showed
      that the soil quality (0-10 cm and 10-20 cm layers) of the three kind meadows was
      in the order of K. humilis meadow > P. froticosa shrub meadow > K. pygmaea
      meadow, and P. froticosa shrub meadow > K. pygmaea meadow > K. humilis meadow,
      respectively.

PMID- 21941740
TI  - [Salinization-alkalization of Leymus chinensis grassland in Songnen Plain of
      Northeast China].
AB  - Field survey and site study were conducted to approach the process and causes of
      salinization-alkalization of Leymus chinensis grassland in Songnen Plain, and to
      examine the hypothesis of soil disturbance-bareness. In the grassland, surface
      soil (0-30 cm) had a lower salt content, while deeper soil (> 30 cm) was in
      adverse. Thereby, the grassland was defined as soil-salted grassland. There was
      an increasing salt content in surface soil. This process was called as soil
      salinization-alkalization, and the grassland under the salinization:alkalization
      was named as alkali-salinized grassland. The leading reason for the surface soil
      salinization-alkalization was that the surface soil originally with low salt
      content was disturbed and lost away, subsurface soil rich in salt emerged as new
      surface soil, and the salt in deeper soil layers accumulated in the new surface
      soil and other soil layers. Secondary halophyte communities formed on the surface
      soil-disturbed new bare land, but the communities had no succession sequence. The
      degradation process of the grassland was soil degradation first, followed by
      vegetation degradation, halophyte invasion, and successive evolution from nearly
      primitive condition.

PMID- 21941741
TI  - [Characteristics of CO2 emission from Carex-dominated wetland in Poyang Lake in
      non-flooded period].
AB  - By using static chamber/gas chromatography, the CO2 fluxes in a Carex cinerascen
      dominated wetland in the Poyang Lake Nanji Wetland National Nature Reserve were
      measured in nonflooded period (from September 2009 to April 2010). Two treatments
      were installed, i. e. , soil-plant system (TC) and aboveground plant removal
      (TJ), representing ecosystem respiration and soil respiration, respectively.
      There was an obvious seasonal variation in the ecosystem respiration and soil
      respiration. The respiration rate in treatment TC ranged from 89.57 to 1243.99 mg
      CO2 x m(-2) x h(-1), and that in TJ was from 75.30 to 960.94 mg CO2 x m(-2) x h(
      1). Soil respiration accounted for 39% -84% of ecosystem respiration, with an
      average of 64%. Soil temperature was the main factor controlling the ecosystem
      respiration and soil respiration, explaining more than 80% of the respiration
      variance. The temperature coefficient (Q10), an index of temperature sensitivity
      for respiration, was 3.31 for ecosystem respiration and 2.75 for soil
      respiration. The Q10 value was higher in winter than in autumn and spring. No
      significant correlation was observed between soil moisture and CO2 fluxes. In non
      flooded period, the C. cinerascens-dominated wetland acted as a carbon sink of
      atmospheric CO2, with a carbon uptake of 1717.72 g C x m(-2).

PMID- 21941742
TI  - [Effects of growth regulators and growth media on root-hair development of
      Poncirus trifoliate].
AB  - By using river sand and mixed soil as growth media, and treating with different
      concentration IBA, ETH, and NAA, this paper studied the root-hair development of
      Poncirus trifoliate seedlings, and the development cycle and distribution pattern
      of the root-hairs under phosphorus deficiency in sand culture. The root-hairs had
      a development cycle of about 4 days, and formed block-shaped and clumped, mainly
      around root, and with uneven distribution. Sand culture gave rise to the
      production of more root hairs, with an average of 486.3 per tap root, and
      treating with 1.0 micromol x L(-1) of IBA and ETH notablypromoted root-hair
      development. The phosphorous deficiency in sand culture induced more roothair
      formation (636.3 per tap root). Mixed soil culture produced lesser root-hairs
      (212.3 per taproot), and all the test growth regulators had no obvious effects on
      the root-hair development.

PMID- 21941743
TI  - [Effects of inoculating arbuscular mycorrhizal fungi on Artemisia annua growth
      and its officinal components].
AB  - A pot experiment was conducted to study the effects of inoculating arbuscular
      mycorrhizal (AM) fungi on the growth, nutrient uptake, and officinal components
      of Artemisia annua. Inoculation with AM fungi Glomus mosseae and G. versiforme
      improved the uptake of nitrogen, phosphorus, and potassium by A. annua, and
      increased the leaf chlorophyll content, net photosynthetic rate, stomatal
      conductance, and transpiration rate as well as the stem diameter and aboveground
      biomass of A. annua, with greater effects of inoculating G. mosseae than G.
      versiforme. After the colonization of G. mosseae and G. versiforme, the
      artemisinin content in A. annua stem, branch, and leaf was increased by 32.8%,
      15.2%, and 19.6%, and 26.5%, 10.1%, and 14.9%, and the volatile oil content in
      leaf was increased by 45.0% and 25. 0%, respectively, compared with the control.
      Furthermore, mycorrhizal colonization led to changes in volatile components.

PMID- 21941744
TI  - [Nitrogen uptake and allocation characteristics of flue-cured tobacco in Nanxiong
      tobacco-planting area of Guangdong Province].
AB  - By the method of field in situ culture and 15N isotopic tracer technique, and
      taking flue-cured tobacco (Nicotiana tobacum) cultivar K326 as test material, a
      field experiment was conducted in the Nanxiong tobacco-planting area of Guangdong
      Province to study the characteristics of soil nitrogen (N) mineralization, the
      patterns of N accumulation and allocation in tobacco plants, and the allocation
      of plant-absorbed fertilizer N applied in current growth season. In the study
      area, the amount of soil mineralized N increased with tobacco growth, peaked at
      75 days after transplanting, and decreased thereafter. The soil mineralized N at
      each tobacco growth stage was significantly higher in the control than in the N
      fertilization treatment. The N accumulation in tobacco plant organs was in the
      order of leaf > stalk > root. Tobacco plants mainly absorbed fertilizer N at
      rosette stage and topping stage, and mainly absorbed soil N at mature stage. The
      absorbed N in tobacco whole growth period was mainly derived from soil N, and the
      absorbed soil N and its proportion to the total absorbed N increased evidently
      with extending growth stage and ascending leaf position. The fertilizer N use
      efficiency per plant and the residual rate and loss rate of applied fertilizer N
      were 30. 8%, 32. 3% , and 36. 9% , respectively. In the study area, soil N
      mineralization rate was relatively high, and soil N had greater effects on the
      quality of upper tobacco leaves. Under the application rate of 150 kg N x hm(-2),
      the residual amount and loss amount of applied fertilizer N were relatively high.

PMID- 21941745
TI  - [Effects of reduced solar radiation on winter wheat flag leaf net photosynthetic
      rate].
AB  - Taking winter wheat Triticum aestivum L. (cv. Yangmai 13) as test material, a
      field experiment was conducted in Nanjing City to study the effects of simulated
      reduced solar radiation on the diurnal variation of winter wheat flag leaf
      photosynthetic rate and the main affecting factors. Five treatments were
      installed, i. e., 15% (T15), 20% (T20) , 40% (T40), 60% (T60), and 100% (CK) of
      total incident solar radiation. Reduced solar irradiance increased the
      chlorophyll and lutein contents significantly, but decreased the net
      photosynthetic rate (Pn). Under different solar irradiance, the diurnal variation
      of Pn had greater difference, and the daily maximum Pn was in the order of CK >
      T60 > T40 > T 20 > T15. In CK, the Pn exhibited a double peak diurnal curve;
      while in the other four treatments, the Pn showed a single peak curve, and the
      peak was lagged behind that of CK. Correlation analysis showed that reduced solar
      irradiance was the main factor affecting the diurnal variation of Pn, but the
      physiological parameters also played important roles in determining the diurnal
      variation of Pn. In treatments T60 and T40, the photosynthesis active radiation
      (PAR), leaf temperature (T1) , stomatal conductance (Gs) , and transpiration rate
      (Tr) were significantly positively correlated with Pn, suggesting their positive
      effects on Pn. The intercellular CO2 concentration (Ci) and stomatal limitation
      (Ls) had significant negative correlations with Pn in treatments T60 and T40 but
      significant positive correlations with Pn in treatments T20 and T15, implying
      that the Ci and Ls had negative (or positive) effects on Pn when the solar
      irradiance was higher (or lower) than 40% of incident solar irradiance.

PMID- 21941746
TI  - [Effects of planting density and spraying PP333 on winter wheat lodging
      resistance and grain yield].
AB  - Taking two winter wheat varieties Gaocheng 8901 and Yannong 21 with different end
      use qualities as test objects, a field experiment was conducted in the
      experimental farm of Shandong Agricultural University from 2008 to 2010, aimed to
      study the effects of different planting density and spraying PP333 on the basal
      stem morphological characteristics, snapping-resistance, lodging-resistant index,
      and grain yield. Gaocheng 8901 had higher lodging-resistance but lower grain
      yield than Yannong 21. Comparing with low planting density (180 x 10(4) basic
      seedlings per hm2), high planting density (240 x 10(4) basic seedlings per hm2)
      decreased the culm snapping-resistance and lodging-resistant index of the two
      varieties, especially Yannong 21. Spraying PP333 decreased the plant height and
      the basal internodes length, increased the snapping-resistance and lodging
      resistant index, strengthened the lodging-resistance, and improved the spike
      number and grain yield. Correlation analysis showed that the second internode
      length, percentage of basal internodes (1 + 2) length to total internode length,
      and apparent lodging ratio were significantly negatively correlated with culm
      lodging resistant index. Therefore, to adopt an appropriate planting density
      combined with spraying PP333 could improve the lodging-resistance of winter wheat
      and its grain yield, being an important high-yielding cultivation technique for
      wheat production in sub-humid zone.

PMID- 21941747
TI  - [Effects of different mulching measures on winter wheat field soil respiration in
      Loess Plateau dry land region].
AB  - A field experiment was conducted to study the effects of different mulching
      measures on the diurnal and seasonal variations of winter wheat field soil
      respiration in dry land region of Loess Plateau. Four treatments were installed,
      i. e., 300 kg x hm(-2) straw mulching (M300), 600 kg x hm(-2) straw mulching
      (M600), plastic film mulching (PM), and no mulching (CK). In all treatments, the
      soil respiration rate had a decreasing trend from autumn to winter, but increased
      rapidly after winter and peaked at jointing stage. Comparing with CK, treatments
      mulching promoted the soil respiration obviously from wintering to maturing
      stage, with significant differences between treatment PM and the others. The
      average soil respiration rate in treatments M300, and M600 in whole growth period
      was 1. 52 micromol CO2 x m(-2) x s(-1) and 1. 47 micromol CO2 x m(-2) x s(-1),
      being 10. 2% and 6.6% higher than the CK (1.38 micromol CO2 x m(-2) s(-1)) ,
      respectively, and that in treatment PM was 3. 63 micromol CO2 x m(-2) x s(-1),
      163% higher than CK. The diurnal variation of soil respiration rate in CK and in
      M300 and M600 presented a single peak curve and peaked at 12:00 and 14:00,
      respectively, but for PM treatment, the diurnal variation of soil respiration
      rate was similar with that in CK at jointing stage while presented a bimodal
      curve at maturing stage, with the peaks at 12:00 and 16:00, respectively. Soil
      respiration rate had an exponential correlation with soil temperature, and a
      parabolic correlation with soil moisture.

PMID- 21941748
TI  - [Freeze resistance analysis of different wheat cultivars based on the
      relationships between physiological indices and grain yield].
AB  - A pot experiment with twenty wheat cultivars was conducted to investigate the
      superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activities and
      the MDA, soluble protein and soluble sugar contents of functional leaves as well
      as the grain yield, 1000-grain weight, and grain morphological characters under
      low temperature stress. Low temperature (-4 degrees C) stress at stem elongation
      stage resulted in the changes of grain morphology and yield characters. For most
      of test cultivars, their grain length-width ratio, grain roundness, and sterile
      spikelets increased, and their grain equivalent diameter, grain area, 1000-grain
      weight, and grain yield decreased. Path analysis indicated that after treated
      with low temperature at stem elongation stage, the SOD activity and soluble sugar
      content of functional leaves, especially the SOD activity (direct path
      coefficient -0. 578) , were the dominant factors affecting grain yield. Taking
      the percentage of decreased grain yield due to low temperature stress as the
      assessment criterion, the test twenty winter wheat cultivars were divided into
      three groups. Cultivars Jimai 19, Jimai 20, Liangxing 99, Shannong 1135, Shannong
      8355, Taishan 23, Taishan 9818, Wennong 6, and Yannong 21 belonged to high freeze
      resistance group, cultivars Linmai 2, Weimai 8, Yannong 19, and Zimai 12 were of
      low freeze resistance group, and the other seven cultivars belonged to medium
      freeze resistance group. The seedling stage comprehensive assessment index (D
      value) had a significant negative correlation with the percentage of decreased
      grain yield (r = -0. 512*), suggesting that the stronger freeze resistance of
      wheat at seedling stage was beneficial to the higher wheat grain yield, and
      seedling stage was the critical period to be selected to identify the freeze
      resistance of wheat.

PMID- 21941749
TI  - [Effects of light quality on rice seedlings growth and physiological
      characteristics].
AB  - By using light emitting diode (LED) to accurately modulate spectral energy
      distribution, and with fluorescent light as the control, this paper studied the
      effects of light quality on the seedlings growth and physiological
      characteristics of rice cultivars 'Wuyunjing 7' and 'Kangyou 63'. Light quality
      had significant effects on the seedlings growth, and there existed differences at
      different growth stages. Blue LED inhibited the height growth significantly, and
      increased the leaf soluble protein content of 'Wuyunjing 7' and the healthy index
      of the two rice cultivars at five-leaf stage. Red LED increased the stem diameter
      and healthy index at three-leaf stage and the leaf soluble sugar and starch
      contents at five-leaf stage significantly. Red-blue LED increased the root
      number, stem diameter, healthy index, root activity, and root soluble sugar
      content at three-leaf stage and the fresh mass, dry mass, healthy index, and leaf
      soluble sugar and sucrose contents at five-leaf stage significantly. Yellow LED
      increased the plant height and leaf pigment content at initial growth stage.
      Overall, red-blue LED was more beneficial to the culture of strong rice
      seedlings.

PMID- 21941750
TI  - [Distribution of Bt protein in transgenic cotton soils].
AB  - A pot experiment with red soil, yellow brown soil, and yellow cinnamon soil was
      conducted to detect the Bt protein content in rhizosphere and non-rhizosphere
      soils at different growth stages of transgenic Bt cotton and common cotton by
      using enzyme linked immunosorbent assay (ELISA). With the planting of transgenic
      Bt cotton, the Bt protein content in rhizosphere soil was significantly higher
      than that in non-rhizosphere soil; while in common cotton soils, there was no
      significant difference in the Bt protein content between rhizosphere soil and non
      rhizosphere soil. At bud stage of transgenic Bt cotton, the Bt protein content in
      rhizosphere soil was in the order of yellow cinnamon soil > yellow brown soil >
      red soil, being 144% 121%, and 238% of that in common cotton rhizosphere soil; at
      florescence stage of transgenic Bt cotton, the Bt protein content in rhizosphere
      soil was in the order of yellow brown soil > yellow cinnamon soil > red soil,
      being 156% , 116% , and 197% of that in common cotton rhizosphere soil,
      respectively. Regardless of planting Bt cotton or common cotton, the Bt protein
      content in rhizosphere and non-rhizosphere soils had an initial increase with the
      growth of cotton, peaked at florescence stage, and then decreased. Throughout the
      whole cotton growth period, the Bt protein content in transgenic Bt cotton
      rhizosphere soil was higher than that in Bt cotton non-rhizosphere soil, and
      also, higher than that in common cotton rhizosphere soil, indicating that
      transgenic Bt cotton could release its Bt protein to rhizosphere soil.

PMID- 21941751
TI  - [Effects of inoculating earthworm on the seed yield and its oil content of winter
      oilseed rape].
AB  - A field experiment was conducted to study the effects of inoculating earthworm
      (Metaphire guillelmi) on the yield components, seed yield, and seed oil content
      of winter oilseed rape (Brassica napus L. cv. Zhongshuang 9). Inoculating
      earthworm increased the primary branch numbers per plant, main raceme pod numbers
      per plant, seed numbers per pod, and 1000-seeds weight, but the effect was not
      significant. However, comparing with the control, inoculating earthworm increased
      the pod number per plant, seed yield per plant, and seed yield of whole plot
      significantly, with the increment being 36.7%, 46.5%, and 29.7%, respectively,
      which could be related to the promotion effect of earthworm on the plant growth
      and its nitrogen uptake at vegetative growth stage. After the inoculation with
      earthworm, the seed oil content somewhat decreased, but, owing to the significant
      increase of seed yield under the effect of earthworm, both the oil production per
      plant and the oil production of whole plot increased significantly by 37.4% and
      21.0%, respectively, compared with the control.

PMID- 21941752
TI  - [Present situation of maize straw resource utilization and its effect in main
      maize production regions of China].
AB  - A survey was carried out in three main maize production regions in Northeast,
      North, and Southwest China, including 720 villages of 125 counties, with the
      purpose of investigating the present situation of maize straw resource
      utilization and its effect. Among the present utilization ways of maize straw
      resource, the main ones were returning to soil, feeding livestock, and using as
      fuel, their proportions being 30.8%, 26.2%, and 24.6%, respectively. In Northeast
      China, the top three utilization ways were fuel, livestock feed, and returning to
      soil, with the proportions being 35.4%, 30.8% and 19.8%; in North China, the top
      three were returning to soil, livestock feed, and fuel, with the proportions
      being 43.6%, 19.9%, and 17.9%; and in Southwest China, they were returning to
      soil, livestock feed, and fuel, with the proportions being 29.0%, 27.9%, and
      20.5%, respectively. In the survey areas, the proportion of using maize straw as
      fuel was smaller (12.8%), and that of using as industrial raw material was only
      0.7%. Returning maize straw to soil increased maize yield (the increment in
      Northeast, North, and Southwest China was 632.0, 371.6, and 290.4 kg x hm(-2),
      respectively), improved soil condition, and decreased the application rates of
      manure, nitrogen, phosphorus, and potassium fertilizers by 20% -30%, 16%-30%, 24%
      34%, and 33%-38%, respectively. The maize yield increased with increasing straw
      mass and its returning amount and proportion. However, because of wanting
      complete sets of available machines, straw returning was low in quality, which
      increased the difficulty in weed controlling and promoted the occurrence of some
      diseases and insect pests, giving impacts on maize seedlings growth. It would be
      necessary to strengthen the researches on the related complete set maize straw
      returning techniques.

PMID- 21941753
TI  - [Changes of China agricultural climate resources under the background of global
      climate change. VI. Change characteristics of precipitation resource and its
      possible effect on maize production in Sanjiang Plain of Heilongjiang Province].
AB  - Based on the 1959-2007 daily precipitation data and 1983-2007 spring maize
      phenologyical data, the thresholds of extreme precipitation at different places
      in Sanjiang Plain of Heilongjiang Province were calculated by percentile method,
      and, in combining with the indices involving the frequency and intensity of
      extreme precipitation, longest consecutive wet (dry) days, and contribution rate
      of extreme precipitation, the annual change characteristics of extreme
      precipitation, quantitative change of different grade precipitation, and
      distribution characteristics of extreme precipitation at each growth stage of
      spring maize were analyzed. In 1959-2007, the annual precipitation in Sanjiang
      Plain showed a slight decreasing trend, and the decreasing amplitude of
      precipitation days was much larger than that of precipitation. Accordingly, the
      annual distribution of precipitation tended to be more concentrated. The
      frequency and intensity of extreme precipitation declined, and the annual
      fluctuation of the frequency was bigger than that of the intensity. There was a
      slight decrease in the proportion of annual extreme precipitation to annual
      precipitation, but the decreasing tendency was not significant. The annual light
      rain days had a significant decreasing trend, but the annual moderate and heavy
      rain days didn't have. During spring maize growth season, the distribution ratio
      of extreme precipitation from high to low was reproductive growth stage,
      coexistence stage of vegetative growth and reproductive growth, vegetative growth
      stage, and premergence stage. There was a significant decrease in the proportion
      of the precipitation during spring maize growth season to annual precipitation,
      resulting in an increasing risk of precipitation scarcity during the growth
      season. The longest consecutive dry days during spring maize growth season showed
      a significant increasing trend, with the increment averaged 1.1 d x (10a)(-1),
      while the longest consecutive wet days showed a significant decreasing trend,
      with the decrement averaged 0.5 d x (10a)(-1). Under natural precipitation, the
      spring maize drought risk in the study region increased.

PMID- 21941754
TI  - [Changes of agroecosystem service value during urbanization of Guangzhou City,
      South China].
AB  - Based on the 1996, 2000, 2004, and 2008 statistical data of Guangzhou City, and
      by the methods of marketing valuation, shadow price, afforestation cost, carbon
      tax, and industrial oxygen-producing, this paper calculated the related service
      values of various agroecosystems in Guangzhou, and assessed the changes of
      agroecosystem service value during the rapid urbanization of the City. In 1996
      2008, though the service values of farmland, grassland, and water ecosystems had
      somewhat increase, the overall agroecosystem service value of Guangzhou
      decreased, mainly due to the more decrease of forest ecosystem service value
      which occupied more than 90% of the total service value each year. Over the
      studied period, the proportion of each individual functional service value to the
      total service value changed little, and the contribution of each individual
      functional service value was in the order of climate regulation > gases
      regulation > product service > waste treatment > soil conservation > biodiversity
      conservation > recreation and culture > water source retention and storage. The
      sum of climate regulation and gases regulation service values took over 91% of
      the total agroecosystem service value. There was a significant negative
      correlation (R = -0.905, P < 0.01)between urbanization rate and total
      agroecosystem service value, suggesting that the increase of urbanization rate
      would lead to a decrease of agroecosystem service value. Therefore, it requires
      an appropriate reservation of various agroecosystems to maintain the regional
      sustainable development during urbanization.

PMID- 21941755
TI  - [Coupling coordinated development of ecological-economic system in Loess
      Plateau].
AB  - Based on system theory, a coupling coordinated development model of ecological
      economic system in Loess Plateau was established, and the evaluation criteria and
      basic types of the coordinated development of the ecological-economic system were
      proposed. The county-level coupling coordinated development of the ecological
      economic system was also discussed, based on the local characteristics. The
      interactions between the ecological and economic systems in Loess Plateau could
      be divided into four stages, i.e., seriously disordered development stage, mild
      disordered development stage, low-level coordinated development stage, and high
      level well-coordinated development stage. At each stage, there existed a cyclic
      process of profit and loss-antagonist-running-dominant-synchronous development.
      The coupling development degree of the ecological-economic system in Loess
      Plateau was overall at a lower level, being about 62.7% of the counties at
      serious disorder, 30.1% of the counties at mild disorder, and 7.1% of the
      counties at low but coordinated level. The coupling development degree based on
      the model established in this study could better reflect the current social
      economic and ecological environment situations, especially the status of
      coordination. To fully understand the coupling of ecological-economic system and
      to adopt appropriate development mode would be of significance to promote the
      county-level coordinated development in Loess Plateau.

PMID- 21941756
TI  - [Atmospheric correction of visible-infrared band FY-3A/MERSI data based on 6S
      model].
AB  - Based on the observation data from the meteorological stations in Taiyuan City
      and its surrounding areas of Shanxi Province, the atmosphere parameters for 6S
      model were supplied, and the atmospheric correction of visible-infrared band
      (precision 250 meters) FY-3A/MERSI data was conducted. After atmospheric
      correction, the range of visible-infrared band FY-3A/MERSI data was widened,
      reflectivity increased, high peak was higher, and distribution histogram was
      smoother. In the meantime, the threshold value of NDVI data reflecting vegetation
      condition increased, and its high peak was higher, more close to the real data.
      Moreover, the color synthesis image of correction data showed more abundant
      information, its brightness increased, contrast enhanced, and the information
      reflected was more close to real.

PMID- 21941757
TI  - [Calculation of regional carbon emission: a case of Guangdong Province].
AB  - By using IPCC carbon emission calculation formula (2006 edition), economy-carbon
      emission dynamic model, and cement carbon emission model, a regional carbon
      emission calculation framework was established, and, taking Guangdong Province as
      a case, its energy consumption carbon emission, cement production CO2 emission,
      and forest carbon sink values in 2008-2050 were predicted, based on the socio
      economic statistical data, energy consumption data, cement production data, and
      forest carbon sink data of the Province. In 2008-2050, the cement production CO2
      emission in the Province would be basically stable, with an annual carbon
      emission being 10-15 Mt C, the energy consumption carbon emission and the total
      carbon emission would be in inverse U-shape, with the peaks occurred in 2035 and
      2036, respectively, and the carbon emission intensity would be decreased
      constantly while the forest carbon sink would have a fluctuated decline. It was
      feasible and reasonable to use the regional carbon emission calculation framework
      established in this paper to calculate the carbon emission in Guangdong Province.

PMID- 21941759
TI  - [Variation characteristics of runoff coefficient of Taizi River basin in 1967
      2006].
AB  - Based on the daily precipitation and runoff data of six main embranchments
      (Haicheng River, Nansha River, Beisha River, Lanhe River, Xihe River, and Taizi
      River south embranchment) of Taizi River basin in 1967-2006, this paper analyzed
      the variation trend of runoff coefficient of the embranchments as well as the
      relationship between this variation trend and precipitation. In 1967-2006, the
      Taizi River south embranchment located in alpine hilly area had the largest mean
      annual runoff coefficient, while the Haicheng River located in plain area had the
      relatively small one. The annual runoff coefficient of the embranchments except
      Nansha River showed a decreasing trend, being more apparent for Taizi River south
      embranchment and Lanhe River. All the embranchments except Xihe River had an
      obvious abrupt change in the annual runoff coefficient, and the beginning year of
      the abrupt change differed with embranchment. Annual precipitation had
      significant effects on the annual runoff coefficient.

PMID- 21941758
TI  - [Application of small remote sensing satellite constellations for environmental
      hazards in wetland landscape mapping: taking Liaohe Delta, Liaoning Province of
      Northeast China as a case].
AB  - To timely and accurately acquire the spatial distribution pattern of wetlands is
      of significance for the dynamic monitoring, conservation, and sustainable
      utilization of wetlands. The small remote sensing satellite constellations A/B
      stars (HJ-1A/1B stars) for environmental hazards were launched by China for
      monitoring terrestrial resources, which could provide a new data source of remote
      sensing image acquisition for retrieving wetland types. Taking Liaohe Delta as a
      case, this paper compared the accuracy of wetland classification map and the area
      of each wetland type retrieved from CCD data (HJ CCD data) and TM5 data, and
      validated and explored the applicability and the applied potential of HJ CCD data
      in wetland resources dynamic monitoring. The results showed that HJ CCD data
      could completely replace Landsat TM5 data in feature extraction and remote
      sensing classification. In real-time monitoring, due to its 2 days of data
      acquisition cycle, HJ CCD data had the priority to Landsat TM5 data (16 days of
      data acquisition cycle).

PMID- 21941760
TI  - [Isolation and identification of a highly efficient pyrene-degrading
      Mycobacterium sp. strain N12].
AB  - By using selective enrichment method, a highly efficient pyrene-degrading
      bacterium strain N12 was isolated from an oil-contaminated soil collected from
      Shenfu irrigation area of Shenyang. Based on the physiological and biochemical
      characteristics and the phylogenetic similarity of 16S rDNA gene sequence, the
      strain N12 was identified as Mycobacterium sp. , which could utilize
      phenanthrene, acenaphthene, fluorine, and pyrene, but not anthracene,
      naphthalene, and benzo (a)pyrene as the sole carbon and energy source. However,
      when the strain N12 was cultured with pyrene and phenanthrene, 79.0% of
      benzo(a)pyrene could be co-metabolized within 9 days. The degradation rate of 100
      mg x L(-1) of pyrene by the strain N12 was 94.4% within 7 days and 100% after 14
      days, and that of 600 mg x L(-1) of pyrene was 56.1% within 7 days and 95.5%
      within 14 days. The addition of glucose promoted the degradation of pyrene. It
      was suggested that the strain N12 was an efficient PAHs-degrading bacterium,
      being a potential candidate for the bioremediation of PAHs-contaminated soils.

PMID- 21941761
TI  - [Main bacterial groups in banana soil under rotated and continuous cropping].
AB  - Banana wilt is the main disease in banana production, while banana-leek rotation
      can effectively control the occurrence of the disease. In order to understand the
      variations of soil bacterial groups under banana-leek rotation and banana
      continuous cropping, soil samples under these two cropping systems were collected
      to extract crude DNA, and the bacterial 16S rDNA in V3 region was amplified by
      PCR. The PCR products were then separated by DGGE, and the main different bands
      were sequenced and compared with the records of NCBI to identify the germs. Under
      banana-leek rotation, soil bacterial diversity was richer, and the main bacterial
      groups were Bacteroidetes, Proteobacteria, Actinobacteria, Chloroflexi, and
      Acidobacteria; while under banana continuous cropping, the soil bacterial
      diversity was somewhat decreased, and the main bacterial groups were Firmicutes,
      Proteobacteria, Actinobacteria, and Chloroflexi.

PMID- 21941762
TI  - [Comparison of two plant-bird mutualistic systems in Asian tropical rainforests].
AB  - Abstract: To deeply understand how the morphological features of plants affect
      the visiting of pollen- and seed dispersal birds is beneficial to elucidate the
      ecological and evolutionary consequences of plant-bird interactions. In this
      paper, a comparative study was conducted on the avian pollen- and seed dispersal
      networks across four tropical rainforest habitats having experienced different
      levels of anthropological disturbance in Southwest China. It was observed that
      the inter-active network of plant-frugivorous bird was highly asymmetrical, while
      that of plant-seed dispersal bird was not asymmetrical. The differences between
      the two networks mainly manifested in the bird abundance, bird movable
      capability, and plant features attracting bird visiting. The understanding of
      these differences allowed us to reveal the mutualistic relationship between plant
      and bird.

PMID- 21941763
TI  - [Butterfly species diversity and its conservation in Wuyunjie National Nature
      Reserve, Hunan Province of China].
AB  - By using line-transect method, an investigation was conducted on the species
      diversity of butterfly in Wuyunjie National Nature Reserve, Changde City of Hunan
      Province from June 2008 to September 2010. Aiming at the main factors including
      plant species richness (D) , mean elevation (E) , average distance from
      stream/river (F), and human interference level (K) that affecting the species
      richness of butterfly in 31 segment-level transects in 4 line-transects, multiple
      regression analysis was made, and the diversity and similarity of the butterfly
      communities in the experimental zone, buffer zone, and core zone of the Reserve
      were compared. A total of 147 butterfly species were collected, belonging to 94
      genera and 10 families, among which, 4 species was nationally conserved species.
      Multiple regression analysis showed that D, E, and K were the three most major
      factors affecting the distribution of butterfly. The species richness of
      butterfly had significant positive correlation with D (P < 0.01), and negative
      correlations with E and K (P < 0.05). The species diversity and evenness index of
      butterfly were higher in core zone than in experimental zone and buffer zone,
      dominance index was the highest in experimental zone, and a higher similarity
      index (0.526) was observed between buffer zone and core zone. To conserve the
      species diversity of butterfly in the Reserve, efforts should be made to protect
      the plant species richness, keep the natural forest succession, decrease the
      human interference properly, and tighten up the management of butterfly habitat.

PMID- 21941764
TI  - [Bioactivity and action modes of bisdemethoxycurcumin against Tetranychus
      cinnabarinus Bois. (Acari:Tetranychidae)].
AB  - This paper determined the contact-killing and fumigant activities of natural
      plant product bisdemethoxycurcumin (BDMC) on the important phytophagous mite
      Tetranychus cinnabarinus (Acari:Tetranychidae) at its different life stages, and
      studied the repellency effects of BDMC on the mite larvae, nymphs, and adults,
      and the inhibition efficiency of BDMC on the female mite oviposition under the
      conditions of 26 degrees C +/- 1 degree C, 60%-80% RH, and light cycle 14L : 10D
      h. The median lethal concentration (LC50) of BDMC at 48 h against female adults
      determined by slide-dip method was 0.433 mg x mL(-1). At concentration 0.883 mg x
      mL(-1) (LC70), the contact-killing activity of BDMC against different life stage
      T. cinnabarinus was in the order of larva > nymph > adult > egg, and the
      corrected mortality of larvae at 24 h and 48 h was 60.0% and 83.3%, respectively.
      BDMC had no obvious fumigant activity against different life stage T.
      cinnabarinus, and the corrected mortality was all less than 3% after treatment 24
      h and 48 h. BDMC had stronger repellency activity against the mite, with the
      repellency rate against larvae at different treatment times all above 85%,
      followed by against nymphs, and that against adults after 72 h being only 47.8%.
      BDMC had obvious oviposition inhibition activity against female adults, with the
      inhibition rate after 120 h reached 89.3%. All the results suggested that the
      main action modes of BDMC against T. cinnabarinus were contact-killing,
      repellency, and oviposition inhibition.

PMID- 21941765
TI  - [Phytoplankton community structure in Mingzhu Lake of Chongming Island,
      Shanghai].
AB  - A preliminary study was conducted on the phytoplankton community structure and
      the annual variation of species diversity in Mingzhu Lake of Chongming Island
      from January to December 2007. A total of 120 phytoplankton species belonging to
      8 phyla and 63 genera were collected, among which, Phormidium tenue, Meismopedia
      tenuissima, M. convoluta, Microcystis incerta and Synedra ulna were the dominant
      species. The mean annual density and biomass of the phytoplankton were 5361.57 x
      10(4) cell x L(-1) and 7.68 mg x L(-1) respectively. There was a significant
      difference in the monthly phytoplankton standing crop (P < 0.01) , being the
      highest in July, but no significant difference was observed among different
      observation stations. The Shannon index and Margalef index of the phytoplankton
      community were higher in spring and winter than in the summer and autumn.
      Biological evaluation indicated that the water quality of Mingzhu Lake was better
      in spring and winter than in the other two seasons, and canonical correlation
      analysis (CCA) suggested that the main factors affecting the phytoplankton
      community were water temperature, followed by total phosphorus, and total
      nitrogen.

PMID- 21941766
TI  - [Genetic structure of wild Macrobrachium nipponense populations in Taihu Lake
      based on microsatellite analysis].
AB  - By using eight highly polymorphic microsatellite DNA loci, this paper analyzed
      the genetic structure of wild Macrobrachium nipponense populations in Taihu Lake.
      For the 15 M. nipponense populations in the Lake, there were at least three of
      the loci presenting heterozygosity deficiency and obvious deviation from Hardy
      Weinberg equilibrium after Bonferroni correction. The observed heterozygosity
      values of the 15 populations were all above 0. 683, displaying a high genetic
      diversity, but the diversity varied obviously with site. For example, the genetic
      diversity of the eastern and southern populations at Dukou and Luxiang was higher
      than that of the western and northern populations at Huazhuang and Yangzhu. For
      the 15 populations, parts of the loci showed heterozygote excess and departure
      from mutation-drift equilibrium, suggesting that the population structure had
      experienced bottleneck effect and the population amount had declined. The AMOVA
      analysis across all the populations and loci showed that the genetic divergence
      among the 15 populations was at a lower level (F(ST) = 0.011 ). 98.9% of the
      genetic variation came from intra-population, and 1.1% came from inter
      population, suggesting that all the M. nipponense populations in the Lake could
      be protected and managed as a single unit in genetic resource. However, the
      genetic distance between Huazhuang and Wutangmen populations reached 0.206, being
      close to the delimitation of species identification. Further studies would be
      needed for the sustainable utilization of the genetic resource of M. nipponense
      in Taihu Lake.

PMID- 21941767
TI  - [Thirty years of US long-term ecological research: characteristics, results, and
      lessons learned of--taking the Virginia Coast Reserve as an example].
AB  - In order to observe and understand long-term and large-scale ecological changes,
      the US National Science Foundation initiated a Long-Term Ecological Research
      (LTER) program in 1980. Over the past 30 years, the US LTER program has achieved
      advances in ecological and social science research, and in the development of
      site-based research infrastructure. This paper attributed the success of the
      program to five characteristics, i.e., 1) consistency of research topics and data
      across the network, 2) long-term time scale of both the research and the program,
      3) flexibility in research content and funding procedures, 4) growth of LTER to
      include international partners, new disciplines such as social science, advanced
      research methods, and cooperation among sites, and 5) sharing of data and
      educational resources. The Virginia Coast Reserve LTER site was taken as an
      example to illustrate how the US LTER works at site level. Some suggestions were
      made on the China long-term ecological research, including strengthening
      institution construction, improving network and inter-site cooperation,
      emphasizing data quality, management, and sharing, reinforcing multidisciplinary
      cooperation, and expanding public influence.

PMID- 21941768
TI  - [Management modes of different ownership forests and their ecological effects: a
      review].
AB  - China is in a critical period for the ownership reform of state-owned and
      collectively owned forests, which desiderates theoretical support and practical
      experience. However, the researches on the management modes of these forests and
      their ecological effects are scarce. In Europe and America, manifold ownership
      forest management has a long history, and relevant experts have made many
      researches on the ownership management contents and modes, as well as their
      effects on forest timber productivity, biodiversity, and landscape feature. To
      summarize and refer to these research harvests is definitely necessary and
      imminence for our forest ownership reform. This paper reviewed the management
      aims, modes, and ecological effects of state-owned and privately owned
      (industrial private and non-industrial private) forests, the parcelization and
      divestiture of forest ownership, and the associated protection policies of
      different ownership forests in the representative countries and regions in Europe
      and North America. The research prospect was also put forward.

PMID- 21941769
TI  - [Landscape classification: research progress and development trend].
AB  - Landscape classification is the basis of the researches on landscape structure,
      process, and function, and also, the prerequisite for landscape evaluation,
      planning, protection, and management, directly affecting the precision and
      practicability of landscape research. This paper reviewed the research progress
      on the landscape classification system, theory, and methodology, and summarized
      the key problems and deficiencies of current researches. Some major landscape
      classification systems, e. g. , LANMAP and MUFIC, were introduced and discussed.
      It was suggested that a qualitative and quantitative comprehensive classification
      based on the ideology of functional structure shape and on the integral
      consideration of landscape classification utility, landscape function, landscape
      structure, physiogeographical factors, and human disturbance intensity should be
      the major research directions in the future. The integration of mapping, 3S
      technology, quantitative mathematics modeling, computer artificial intelligence,
      and professional knowledge to enhance the precision of landscape classification
      would be the key issues and the development trend in the researches of landscape
      classification.

PMID- 21941770
TI  - [Effects of agricultural practices on community structure of arbuscular
      mycorrhizal fungi in agricultural ecosystem: a review].
AB  - Arbuscular mycorrhizal (AM) fungi are rich in diversity in agricultural
      ecosystem, playing a vital role based on their unique community structure. Host
      plants and environmental factors have important effects on AM fungal community
      structure, so do the agricultural practices which deserve to pay attention to.
      This paper summarized the research advances in the effects of agricultural
      practices such as irrigation, fertilization, crop rotation, intercropping,
      tillage, and pesticide application on AM fungal community structure, analyzed the
      related possible mechanisms, discussed the possible ways in improving AM fungal
      community structure in agricultural ecosystem, and put forward a set of
      countermeasures, i.e., improving fertilization system and related integrated
      techniques, increasing plant diversity in agricultural ecosystem, and inoculating
      AM fungi, to enhance the AM fungal diversity in agricultural ecosystem. The
      existing problems in current agricultural practices and further research
      directions were also proposed.

PMID- 21941771
TI  - [Microbial degradation of microcystins in water environment: a review].
AB  - Lake and reservoir' s eutrophication and its produced microcystins (MCs) have
      enormous threats to ecological environment and human health. Because the
      conventional water pollution control techniques have definite limitations, it' s
      quite urgent to develop new technique to remove the MCs from water environment.
      MCs can be effectively degraded by specific microbes, and its intermediate and
      terminal products are non-toxic or low-toxic. This paper summarized the MCs
      degrading microbial strains, biodegradation processes, mechanisms, and affecting
      factors, degraded products and their structural characteristics, and the
      applications of MCs-degrading microbial strains in water environment restoration.
      The further research directions were also proposed. It was hoped that this review
      could provide technical ideas for restoring MCs-polluted lakes and reservoirs and
      ensuring drinking water safety in China.

PMID- 21941772
TI  - [Effects of elevated atmospheric CO2 concentration and nitrogen addition on the
      growth of Calamagrostis angustifolia in Sanjiang Plain freshwater marsh].
AB  - By using open top chamber, an experiment with two levels of atmospheric CO2
      concentration (350 and 700 micromol x mol(-1)) and three levels of nitrogen
      supply (0, 5, and 15 g N x m(-2)) was conducted to investigate the effects of
      elevated atmospheric CO2 and nitrogen supply on the growth of Calamagrostis
      angustifolia in the freshwater marsh of Sanjiang Plain. Under elevated
      atmospheric CO2 concentration, the phenophase of C. angustifolia advanced.
      Jointing stage was advanced by 1-2 d, and maturity stage was advanced by 3 d.
      Elevated atmospheric CO2 promoted the tillering of C. angustifolia, with the
      increment of tiller number under 0, 5, and 15 g x m(-2) of nitrogen supply being
      8.2% (P < 0.05), 8.4% (P < 0.05), and 5.5% (P > 0.05), respectively. Elevated
      atmospheric CO2 also promoted the aboveground biomass at jointing and heading
      stages, the increment being 12.4% and 20.9% (P < 0.05), respectively, and
      increased the belowground biomass at later growth stages, with the increment at
      dough stage and maturity stage being 20.5% and 20.9% (P < 0.05), respectively.
      The responses of C. angustifolia biomass to elevated atmospheric CO2
      concentration depended on nitrogen supply level. Under sufficient nitrogen
      supply, the promotion effect of elevated atmospheric CO2 concentration on the
      biomass of C. angustifolia was higher.

PMID- 21941773
TI  - [Roles of DNA dependent protein kinase in silica-induced cyclin E and CDK2
      expressions and cell cycle changes in human embryo lung fibroblasts].
AB  - OBJECTIVE: To study the roles of DNA dependent protein kinase (DNA-PK)in silica
      induced cell cycle changes and expressions of CyclinE and CDK2 in human embryo
      lung fibroblasts (HELF). METHODS: The expressions of Ku80 and DNA-PKcs proteins
      were inhibited by siRNA plasmids, respectively. Flow cytometry was used to detect
      the distributions of cell cycle and western blot assay was used to determine the
      expression levels of CyclinE and CDK2 after cells were exposed to 200 microg/ml
      silica for 0, 3, 6, 12, 24 h. RESULTS: The proportion of G1 phases in negative
      control cells decreased from 83.53% +/- 2.24% to 69.11% +/- 3.12% after exposure
      to silica; the proportion of G1 phases in H-Ku80 and H-PKcs cells exposed to
      silica decreased from 85.16% +/- 3.73% to 59.92% +/- 3.31% and from 75.06% +/-
      2.23% to 58.32% +/- 1.35%, respectively (P < 0.05). The exposure to silica
      resulted in the increasing protein expression levels of CyclinE and CDK2 in
      negative control cells, and the expression levels of CyclinE were obviously
      suppressed in H-Ku80 and H-PKcs as compared with control cells. However, the
      expression level of CDK2 protein did not change significantly. CONCLUSION: DNA-PK
      might play a role in silica-induced alternations of cell cycle and regulate
      silica-induced overexpression of CyclinE in human embryo lung fibroblasts.

PMID- 21941774
TI  - [Effects of silicotic alveolar macrophages exposed to SiO2 on the expression of
      type III collagen and type III procollagen in human lung fibroblasts].
AB  - Effects of silicotic alveolar macrophages exposed to SiO2 on the expression of
      type III collagen and type OBJECTIVE: To study the effects of supernatant of
      alveolar macrophages (AM) exposed to SiO2 on the expression of type III collagen
      and type III procollagen in human lung fibroblasts (HELF) and the intervention
      effects of anti-TGF-beta1 antibody. METHODS: AMs collected from a silicotic by
      bronchoalveolar lavage were divided into 2 parts, one part was exposed to SiO2
      and other part served as control. The supernatant was obtained from AMs cultured
      for 18 h. HELF were divided into (1) exposure group, which was added with
      supernatant from AMs exposed to SiO2; (2) control group, which was added with the
      supernatant from AMs not exposed to SiO2; (3) blank control group, which was
      added with DMEM; (4) exposure group plus anti-TGF-beta1 antibody (10 microg/ml);
      (5) control group plus anti-TGF-beta1 antibody (10 microg/ml). (1)-(3) groups
      were cultured for 6, 12, 18, 24, 36, 48h, respectively. (4)-(5) groups were
      cultured for 18, 24, 36, respectively. Immunocytochemical test and Western blot
      assay were used to detect pC III expression levels in HELF and C III expression
      levels in the supernatant of HELF culture, respectively. RESULTS: The pC III
      expression levels of exposure group were 0.1423 +/- 0.0107, 0.1624 +/- 0.0011,
      0.1925 +/- 0.0050, 0.2421 +/- 0.0097 and 0.2103 +/- 0.0103, respectively, which
      were significantly higher than those (0.1212 +/- 0.0079, 0.1414 +/- 0.0058,
      0.1620 +/- 0.0081, 0.1965 +/- 0.0103, 0.1715 +/- 0.0116) of control group (P <
      0.05 or P < 0.01). The C III levels of exposure group were (0.2559 +/- 0.0061,
      0.3249 +/- 0.0110, 0.4171 +/- 0.0193, 0.5441 +/- 0.0452, 0.4751 +/- 0.0252),
      respectively, which were significantly higher than control group (0.2296 +/-
      0.0121, 0.2778 +/- 0.0116, 0.3367 +/- 0.0269, 0.3722 +/- 0.0214). The pC III and
      C III expression levels of exposure plus anti-TGF-beta1 antibody group were
      significantly lower than those of control plus anti-TGF-beta1 antibody group (P <
      0.05 or P < 0.01). CONCLUSION: AMs exposed to SiO2 can induce the elevated pC
      IIII and C III expression levels in HELF by TGFbetaP1 to some extent.

PMID- 21941775
TI  - [Effects of oxidative stress and NF-kappaB levels in peripheral blood mononuclear
      cells on development of silicosis].
AB  - OBJECTIVE: To investigate the change of indicators of oxidative stress in serum
      and NF-kappaB in peripheral blood mononuclear cells of patients with silicosis,
      and explore the mechanism of the development of silicosis. METHODS: The subjects
      were divided into (1) 200 workers exposed to SiO2 for at least 1 years in a
      foundry served as the dust-exposure group; (2) 130 cases with silicosis (I phase
      silicosis 64 cases, II phase 46 cases III phase 20 cases) served as the silicosis
      group; (3) 32 cases with 0+ phase silicosis in the foundry served as the observed
      group,(4)100 subjects from a hotel served as the control group. The serum
      including superoxide dismutase (SOD), nitric oxide (NO), serum glutathione
      peroxidase (GSH-Px), total antioxidant capacity (T-AOC), nitric oxide synthase
      (NOS), lipid malondialdehyde (MDA) and NF-kappaB protein levels in peripheral
      blood mononuclear cells were determined, respectively. RESULTS: Compared with the
      control group, NO levels in dust-exposed group and silicosis group significantly
      increased, and SOD decreased significantly (P < 0.05 or P < 0.01). Compared with
      the control group and dust-exposed group, T-AOC, NOS, MDA levels in silicosis
      group significantly increased (P < 0.05 or P < 0.01). GSH-Px in dust-exposed
      group and silicosis group were (231.164 +/- 36.484) and (270.469 +/- 39.228)U/ml,
      respectively which were significantly than that [(223.360 +/- 46.838) U/ml] in
      control group (P < 0.05 or P < 0.01), and there was significant difference of
      GSHPx between the silicosis group and the dust-exposed group significantly (P <
      0.01) . GSH-Px level [(290.750 +/- 39.129) U/ml] in III phase silicosis group
      were significantly higher than those [(256.906 +/- 21.41) and (259.594 +/- 34.79)
      U/ml] in observation group and I phase silicosis group (P < 0.05). NF-kappaB
      levels [(72.06 +/- 9.12) and (85.25 +/- 11.64) ng/L] in dust-exposed group and
      silicosis group were significantly higher than that [(59.71 +/- 9.27) ng/L] in
      control group (P < 0.01), and there was significant difference of between the
      silicosis group and the dust-exposed group (P < 0.01). There was a positive
      correlation between serum GSH-Px level and the silicosis stages (r = 0.507, P <
      0.01). Also there was a positive correlation between NF-kappaB level and
      silicosis stages, age, GSH-Px or NO levels (r = 0.376, 0.243, 0.233, 0.221, P <
      0.01). CONCLUSION: The imbalance of oxidative and anti-oxidation system and the
      activation of NF-kappaB are related with the occurrence and development of
      silicosis. The monitoring of oxidative stress indicators and NF-kappaB is
      beneficial to the prediction and prognosis assessment of silicosis.

PMID- 21941776
TI  - [Effect of schisandrin B on lung mRNA expression of transforming growth factor
      beta1 signal transduction molecule in rat lungs exposed to silica].
AB  - OBJECTIVE: To investigate the effects of schisandrin B (Sch-B) on expression of
      transforming growth factor-beta1 (TGF-beta1) and signal transduction molecule
      mRNA in rat lungs exposed to SiO2, and explore the intervention mechanism of Sch
      B on pulmonary fibrosis induced by SiO2. METHODS: Ninety six Wistar rats were
      randomly divided into control (normal saline) group, SiO2 group and SiO2 plus Sch
      B group. The rats were exposed to SiO2 by direct tracheal instillation to
      establish the silicotic animal models. SiO2 group and SiO2 plus Sch-B group were
      treated with 1 ml SiO2 (50 mg/ml) for each rat From the first day after model
      establishment, SiO2 plus Sch-B group were orally given Sch-B (80 mg/kg) a day,
      control group and silica group were orally given olive oil. On the 3rd, 7th, 14th
      and 28th days after treatment, 8 rats in each group were sacrificed and samples
      were collected. The histo-pathological examination of lung was performed by HE
      staining. The expression levels of TGF-beta1, TGF-betaR II and Smad4 mRNA in the
      lung tissues were detected by RT-PCR. RESULTS: The results of histo-pathological
      examination showed that in SiO2 group, lung tissues were injured obviously; the
      alveolar inflammation with alveolus interval edema and inflammation cell
      infiltration appeared on the 3rd and 7th days; the alveolus interval became
      thicker, became thicker, fibroblast and collagen matrix increased markedly on
      14th day; the alveolar structure was damaged, alveolar wall thickened obviously,
      collagen aggravation and pulmonary fibrosis displayed on 28th day. The alveolar
      inflammation and pulmonary fibrosis in SiO2 plus Sch-B group were significantly
      less than those in SiO2 group. The expressions levels of TGF-beta1 TGF-betaR II
      and Smad4 mRNA (TGF-1beta: 1.03 +/- 0.31, 1.33 +/- 0.39,1.08 +/- 0.26, 0.82 +/-
      0.16, TGF-betaR II: 0.65 +/- 0.11, 0.80 +/- 0.16, 0.83 +/- 0.24, 0.62 +/- 0.15,
      Smad4:0.87 +/- 0.15, 0.68 +/- 0.11, 0.78 +/- 0.19, 0.30 +/- 0.08) in SiO2 group
      were significantly higher than those in the control group (TGF-beta1:0.59 +/-
      0.22, 0.55 +/- 0.25, 0.56 +/- 0.20, 0.55 +/- 0.12, TGR-betaR II :0.28 +/- 0.13,
      0.31 +/- 0.15, 0.34 +/- 0.15, 0.27 +/- 0.09, Smad4:0.23 +/- 0.11, 0.40 +/- 0.12,
      0.39 +/- 0.12, 0.18 +/- 0.06) (P < 0.01 or P < 0.05), but the expression level of
      TGF-beta1 mRNA was the highest on the 7th day. The expression levels of TGF-beta1
      and Smad4 mRNA (TGF-beta1:0.68 +/- 0.28, 0.88 +/- 0.25, 0.75 +/- 0.11, 0.61 +/-
      0.14,Smad4:0.25 +/- 0.12, 0.45 +/- 0.09, 0.44 +/- 0.07, 0.21 +/- 0.04) in SiO2
      plus Sch-B group were significantly lower than those in SiO2 group (P < 0.01 or P
      < 0.05 ), but there were no significant differences of the TGFbetaR II mRNA
      expression levels between SiO2 group and SiO2 plus Sch-B group. CONCLUSION: Sch-B
      can reduce the pulmonary fibrosis induced by SiO2 through inhibition of the mRNA
      express of TGF-beta1 and Smad4 in the lung tissue, modulating the TGF-beta1/Smad4
      signal transduction pathway and inhibiting the target gene activation.

PMID- 21941777
TI  - [Involvement of excitatory amino acid system in astrocytes activation caused by
      dimethoate].
AB  - OBJECTIVE: To study the involvement of excitatory amino acid system in astrocytes
      activation caused by dimethoate. METHODS: Pure-cultured astrocytes were gained by
      three passages from primary cultured rat nerve cells, then treated with 10(
      6),10(-5),10(-4) mol/L dimethoate for 48 h, 50 micromol/L and 100 micromol/L
      MK801, a NMDA receptor blocker, was used to intervene the effects induced by 10(
      4) mol/L dimethoate. HPLC-FLD was utilized to measure the concentrations of
      excitatory amino acid (EAA), RT-PCR was used to detect the expression levels of
      NR2B, GLT-1, GLAST, GFAP and S100beta mRNA, and immunofluorescence staining
      method was applied to measure the expression levels of GFAP and S100beta
      proteins. RESULTS: The expression levels of GLAST mRNA in all exposure groups
      were 67.8%, 68.6% and 76.2% of control level, respectively, which were
      significantly lower than that of control group (P < 0.05); The concentrations of
      EAA significantly decreased in 10(-4) mol/L dimethoate group, as compared with
      control group (P < 0.01); the expression levels of GFAP mRNA in 10(-4) mol/L
      dimethoate group, of S100beta mRNA in 10(-5) mol/L dimethoate group, of GFAP
      protein in 10(-4) mol/L and 10(-5) mol/L dimethoate groups and S100beta protein
      in 10(-4) mol/L dimethoate group were significantly higher than those in control
      group (P < 0.01). The expression levels of GLT-1 and GLAST mRNA in 10(-4) mol/L
      dimethoate plus 50 micromol/L or 100 micromol/L MK801 groups increased
      significantly, as compared with 10(-4) mol/L dimethoate group (P < 0.01), the
      expression levels of NR2B mRNA in 10(-4) mol/L dimethoate plus 50 micromol/L or
      100 micromol/L MK801 groups increased significantly, as compared with control
      group (P < 0.05 or P < 0.01); the concentration of Glu in 10(-4) mol/L dimethoate
      plus 100 micromol/L MK801 group increased significantly, as compared with 10(-4)
      mol/L dimethoate group (P < 0.01); the expression levels of GFAP mRNA and protein
      in 10(-4) mol/L dimethoate plus 50 micromol/L or 100 micromol/L MK801 groups
      decreased significantly (P < 0.01); S100beta protein expression level in 50
      micromol/L MK801 intervention group was significantly higher than thatl in
      control group (P < 0.01). CONCLUSION: Excitatory amino acid system involved in
      astrocytes activation caused by dimethoate. MK801 was useful to control
      astrocytes gliosis.

PMID- 21941778
TI  - [Studying the therapeutic effects of hemoperfusion with continuous venovenous
      hemofiltration on the patients with acute paraquat poisoning].
AB  - OBJECTIVE: To explore the therapeutic effects of hemoperfusion (HP) with
      continuous venovenous hemofiltration (CVVH) on the patients with acute paraquat
      poisoning. METHODS: Ninety-one patients with acute paraquat poisoning were
      randomly divided into HP group (49 cases) and HP-CVVH group (42 cases). The
      mortality, survival duration and the death causes between the two groups were
      compared and analyzed. RESULTS: There were no significant differences in
      mortality (59.2% versus 61.9%) between the two groups. The mean time between
      poisoning and death in HP-CVVH group was (4.9 +/- 3.1) days, which was
      significantly longer than that (3.5 +/- 2.0) days in HP group (P < 0.05). The
      death proportion on 4th day after poisoning in HP group was 62.1% (18/29), which
      was significantly higher than that (30.8%, 8/26) in HP-CVVH group (P < 0.05). The
      hypoxia appeared in 4.3 +/- 2.5 days after poisoning in HP-CVVH group, which was
      significantly longer than that (3.2 +/- 1.9) days in HP group (P < 0.05). The
      mortality due to respiratory failure in HP group was 20.4% (10/49), which was
      significantly lower than that (40.5%, 17/42) in HP-CVVH group (P < 0.05). The
      incidence of acute renal failure in HP group was 63.3% (31/49), which was
      significantly higher than that (40.5%, 17/42) in HP-CVVH group (P < 0.05).
      CONCLUSION: The combined therapy of HP and CVVH can prevent the patients with
      acute paraquat poisoning from early death and prolong the survival duration, but
      can not reduce mortality for the patients with acute paraquat poisoning.

PMID- 21941779
TI  - [Antagonism of tert-butylhydroquinone on neurotoxicity and oxidative stress
      induced by paraquat in PC12].
AB  - OBJECTIVE: To investigate the protective effects of the tert-butylhydroquinone
      (tBHQ) pretreatment on neurotoxicity and oxidative stress induced by paraquat
      (PQ) in PC12 cells. METHODS: Cytotoxicity of PC12 cells was measured by MTT
      assay, following the PC12 cells treatment with different concentrations of 100,
      300 micromol/L PQ for 24 h and 48 h. PC12 cells were pretreated with or without
      40 micromol/L tBHQ for 4 h, PC12 cells were exposed to PQ at the doses of 0, 100,
      300 micromol/L for 24 h and 48 h, respectively. The viability of PC12 cells was
      measured by MTT assay, the apoptosis rates of PC12 cells were detected by flow
      cytometry (FCM) and the malondialdehyde (MDA) levels of PC12 cells were examine
      by thiobarbituric acid (TBA) method. RESULTS: When the exposure doses of PQ were
      100 and 300 micromol/L for 24 h, the viability of PC12 cells pretreated with tBHQ
      was significantly higher than that of PC12 cells only exposed to PQ (P < 0.05 or
      P < 0.01). When the exposure dose of PQ was 100 micromol/L for 48 h, the
      viability of PC12 cells pretreated with tBHQ was significantly higher than that
      of PC12 cells only exposed to PQ (P < 0.01). When the exposure doses of PQ were
      100 and 300 micromol/L for 24 h, the apoptosis rates and MDA levels of PC12 cells
      pretreated with tBHQ were significantly lower than those of PC12 cells only
      exposed to PQ (P < 0.05 or P < 0.01). CONCLUSIONS: tBHQ pretreatment can reduce
      the cytotoxicity, apoptosis and oxidative stress induced by PQ in PC12 cells.

PMID- 21941780
TI  - [The application of mechanical ventilation in whole lung lavage of
      pneumoconiosis].

PMID- 21941781
TI  - [The developmental neurotoxic effects in offspring of pregnant rats exposed to
      benzo[a]pyrene].
AB  - OBJECTIVE: To study the effects of prenatal exposure to benzo[a]pyrene (B[a]P) on
      the physical development, early behavioral development, the adaptability to new
      environment and the learning and memory ability of rat offspring. METHODS:
      Pregnant rats were randomly divided into five groups: control group, olive oil
      group, 3 exposure groups (25, 50 and 100 mg/kg B [a]P). The rats were exposed to
      B [a]P) by intraperitoneal injection on the 17th-19th days during gestation. The
      offspring were weighed on postnatal days (PND)1, PND 4, PND 7 and PND 28, the
      indices of physical development, reflective ability and sensory function were
      detected for offspring, the Morris water maze and Open-field tests were used to
      measure the ability of learning and memory and the adaptability to new
      environment of offspring. RESULTS: The time of ear opening in middle and high
      dose groups [(4.1 +/- 0.4),(5.0 +/-0.4) d] was posterior to that in untreated and
      solvent groups [(3.3 +/- 0.5), (3.4 +/- 0.6) d ](P < 0.01). The attainment rate
      (6.5%) of the surface righting reflex test in high-dose group on the 4th day was
      significantly lower than that (36.1%) in untreated group, the attainment rate
      (50.0%) in high-dose group on PND7 was significantly lower than those (81.3% and
      79.3%) in untreated group and solvent group (P < 0.05). Compared to the untreated
      group, the time of forelimb hanging test in all exposure groups on PND12 and
      PND14 significantly decreased; compared to the solvent group the time of forelimb
      hanging test decreased in high-dose group on the 14th day significantly decreased
      (P < 0.01). The attainment rate (61.9%) of olfactory discrimination in high-dose
      group on PND12 was significantly lower than that (94.3%) in untreated group (P <
      0.05). The results of Morris water maze test showed that the escape latency of
      different dose groups significantly increased, and the time of spatial probe and
      the times of traversing flat in high-dose group decreased significantly, as
      compared to the untreated and solvent groups (P < 0.01). The results of open
      field test indicated that the center retention time in middle and high-dose
      groups significantly prolonged, the times of crossing lattice obviously reduced,
      and the rearing times decreased in high-dose group, as compared to untreated (P <
      0.05).Compared to the solvent group, the times of crossing lattice in all
      exposure groups reduced significantly (P < 0.01 or P < 0.05). CONCLUSION: The
      prenatal exposure to B[a]P could inhibit the physical development and early
      behavioral development, and influence the adaptability to new environment and
      learning and memory ability for offspring.

PMID- 21941782
TI  - [Effect of ulinastatin on the expression of heat shock protein 70 and NF-kappaB
      in lung tissue in rats with paraquat poisoned].
AB  - OBJECTIVE: To observe the expression levels of heat shock protein 70 (hsp70) and
      NF-kappaB p65 mRNA in lung tissue of acute paraquat (PQ) poisoning rats, and
      intervention effects of ulinastatin (UTI). METHODS: Seventy-two Sprague-Dawley
      (SD) rats were randomly divided into three groups: PQ poisoning group, UTI group
      and control group. The rats were exposed intragastrically to PQ at the dose of 80
      mg/kg to establish a model of the rat acute lung injury. The UTI group was
      intervened by peritoneal injection with 10000 U/kg UTI in 30 minutes. On the 12,
      24, 48, 72 h after exposure, myeloperoxidase (MPO) activity in lung tissue were
      detected. The expression of the NF-kappaB p65 mRNA and hsp70 mRNA in lung tissue
      was detected by the reverse transcription-PCR (RT-PCR). The lung pathological
      changes of rats were observed. RESULTS: The degree of lung injury in PQ group and
      UTI group was higher than that in control group. But in UTI group the degree of
      lung injury was lower than PQ group. MPO activity in the lung tissues in PQ group
      was (31.72 +/- 6.42), (56.23 +/- 8.63), (87.21 +/- 10.02) and (107.21 +/- 13.52)
      micro/g in 12, 24, 48 and 72 h, respectively which was significantly higher than
      that [(11.38 +/- 1.25) micro/g] in control group (P < 0.01). MPO activity in the
      lung tissues in UTI group was (15.65 +/- 3.21), (35.98 +/- 5.74), (59.33 +/-
      9.65) and (71.25 +/- 10.58) micro/g in 12, 24, 48 and 72 h, respectively which
      was significantly lower than those in PQ group (P < 0.01). The expression levels
      of NF-kappaB p65 mRNA of lung tissues in UTI group in 12, 24, 48 and 72 h were
      0.3288 +/- 0.0147, 0.5337 +/- 0.0328, 0.7357 +/- 0.0424 and 0.7547 +/- 0.0905,
      respectively, which were significantly lower that those (0.4185 +/- 0.0294,
      0.8532 +/- 0.0841, 0.9554 +/- 0.0975 and 1.0094 +/- 0.0703) in PQ group (P <
      0.01). hsp70 mRNA expression levels in 12, 24, 48 and 72 h of the UTI group were
      0.5193 +/- 0.0254, 0.8289 +/- 0.0606, 0.7566 +/- 0.0277 and 0.4873 +/- 0.0105,
      respectively, which were significantly higher than those (0.3897 +/- 0.0125,
      0.5904 +/- 0.0186, 0.4007 +/- 0.0237 and 0.2293 +/- 0.0137) in PQ group (P <
      0.01). CONCLUSION: The expression levels of hsp70 mRNA and NF-kappaB p65 mRNA of
      rats after intoxication increased significantly. UTI can protect the lung tissues
      by elevating the expression of hsp70 and reducing the expression of NF-kappaB in
      the lung tissues of rats with acute paraquat poisoning.

PMID- 21941783
TI  - [Effects of postnatal lambda-cyhalothrin exposure on synaptic proteins in ICR
      mouse brain].
AB  - OBJECTIVE: To evaluate the influence on the synaptic protein expression in
      different brain regions of ICR mice after lambda-cyhalothrin (LCT) exposure
      during postnatal period. METHODS: Two male and 4 female healthy ICR mice were put
      in one cage. It was set as pregnancy if vaginal plug was founded. Offspring were
      divided into 5 groups randomly, and exposed to LCT (0.01% DMSO solution) at the
      doses of 0.1, 1.0 and 10.0 mg/kg by intragastric rout every other day from
      postnatal days (PND) 5 to PND13, control animals were treated with normal saline
      or DMSO by the same route. The brains were removed from pups on PND 14, the
      synaptic protein expression levels in cortex, hippocampus and striatum were
      measured by western blot. RESULTS: GFAP levels of cortex and hippocampus in the
      LCT exposure group increased with doses, as compared with control group (P <
      0.05), while Tuj protein expression did not change significantly in the various
      brain regions of ICR mice. GAP-43 protein expression levels in the LCT exposed
      mouse hippocampus and in female ICR mouse cortex increased with doses, as
      compared with control group (P < 0.05). Presynaptic protein (Synapsin I)
      expression levels did not change obviously in various brain regions. However,
      postsynaptic density protein 95 (PSD95) expression levels of the hippocampus and
      striatum in male offspring of 10.0 mg/kg LCT group, of cortex of female LCT
      groups, and of female offspring in all exposure groups, of striatum, in 1.0 or
      10.0 mg/kg LCT exposure groups significantly decreased (P < 0.05). CONCLUSIONS:
      Early postnatal exposure to LCT affects synaptic protein expression. These
      effects may ultimately affect the construction of synaptic connections.

PMID- 21941784
TI  - [Effects of dexamethasone pretreatment on expression of matrix metalloproteinase
      9 in rats with acute lung injury induced by phosgene].
AB  - OBJECTIVE: To investigate the effects of dexamethasone on expression of matrix
      metalloproteinase-9 (MMP-9) in rats with acute lung injury induced by phosgene.
      METHODS: The rats were randomly divided into 3 groups: normal control group that
      consists of the rats with air exposure, phosgene group that consists of the rats
      with phosgene exposure and dexamethasone group that consists of the rats with
      phosgene exposure after 2.5 mg/kg dexamethasone being injected. Wet and dry ratio
      of the lung (W/D) was calculated, and leukocyte count and total protein content
      of bronchoalveolar lavage fluid (BALF) were recorded at 2 h after exposure. The
      concentrations of MMP-9 in the serum and BALF were measured by enzyme-linked
      immunosorbent assay. The pathologic changes of lung tissues were observed under
      light microscopy. The immunohistochemistry and the RT-PCR were used to detect the
      contents of MMP-9 in the lung tissue. RESULTS: Compared with phosgene group, the
      lung W/D, protein content and WBC count in of BALF dexamethasone group was
      significantly decreased (P < 0.01). MMP-9 levels of the serum and BALF in
      dexamethasone group were (4.799 +/- 0.043) microg/L and (15.052 +/- 0.029)
      microg/L, respectively, which were significantly lower than those [(9.439 +/-
      0.100) and (20.640 +/- 0.446) microg/L] in phosgene group (P < 0.01). Compared
      with phosgene group (2.789 +/- 0.282),the expression level (1.183 +/- 0.260) of
      lung MMP-9 mRNA in dexamethasone group was significantly lower than that in
      phosgene group (P < 0.01). Histological experimental results showed the marked
      hyperemia and thickening of alveolar walls and stroma cells infiltrating and more
      visible alveolar structure damage of alveolar walls in phosgene group while the
      alveolar structure and the alveolar walls were clear and slightly thickened with
      inflammatory cells in dexamethasone group. Immunohistochemical results showed
      that MMP-9 protein expression levels of lung and bronchus tissues in normal
      control group and dexamethasone group were weakly positive, which in phosgene
      group were strongly positive. CONCLUSION: Dexamethasone has a beneficial effects
      on acute lung injury induced by phosgene in rats due to the inhibiting MMP-9.

PMID- 21941785
TI  - [Studying the lipid peroxidation index, morphology and apoptosis in testis of
      male BALB/c mice exposed to polybrominated diphenyl ether (BDE-209)].
AB  - OBJECTIVE: To explore the lipid peroxidation and the testicular morphological
      change induced by decabrominated diphenyl ether (BDE-209) in male BALB/c mice.
      METHODS: Twenty one male BALB/c mice were randomly divided into three groups: the
      high exposure group (500 mg/kg BDE-209), the low exposure group (200 mg/kg BDE
      20) and control group (normal saline). The mice were exposed by gavage one time a
      day for 6 weeks, then were sacrificed. Body weight, testis weight,
      malonyldialdehyde (MDA), total superoxide dismutase (T-SOD) and glutathione (GSH)
      in testis were examined. The morphological alteration of testis was observed.
      TUNEL assay was used to detect the apoptosis in testicular cells. RESULTS: Body
      weight and testis weight in high and low exposure groups were (21.6140 +/-
      2.3550) g, (20.8000 +/- 1.7630) g and (0.1859 +/- 0.0349) g, (0.1718 +/- 0.0266)
      g, respectively, which were significantly lower than those (27.7570 +/- 1.2880) g
      and (0.2302 +/- 0.0335) g in the control group (P < 0.05); the testis coefficient
      in high exposure group was (0.8640% +/- 0.1706%), which was significantly higher
      than that (0.8329 +/- 0.1386%) in the control group (P < 0.05). The GSH level and
      SOD activities of testis in 2 BDE-209 groups were 0.044 +/- 0.006, 0.039 +/-
      0.005 nmol/mg prot, and 0.735 +/- 0.179, 0.907 +/- 0.198 U/mg prot, respectively,
      which were significantly lower than those (0.052 +/- 0.067) mol/mg and (1.161 +/-
      0.188) U/mg in the control group (P < 0.05). The levels of MDA in 2 BDE-209
      groups were (2.365 +/- 0.339) and (1.752 +/- 0.366) nmol/mg prot, which were
      significantly higher than that (1.173 +/- 0.232 nmol/mg prot) in control group (P
      < 0.05). there were significant differences of SOD and MDA levels between high
      exposure group and low exposure group (P < 0.05). Histological examination showed
      that the number of spermatogenic cells and layer were decreased significantly in
      2 exposure groups as compared with control group. TUNEL assay showed that
      apoptosis cells appeared in 2 exposure groups. CONCLUSION: BDE-209 changed lipid
      peroxidation in male BALB/c mice testis and caused toxic effects on the testis.

PMID- 21941786
TI  - [Study on activities and protein and gene expression of renal H(+)-K(+)-ATPase in
      rats subchronic exposed to trimethyltin chloride].
AB  - OBJECTIVE: To study the activity, protein and gene expression of renal HK-ATPase
      (HKA) in rats subchronic exposed to trimethyltin chloride (TMT). METHODS: In
      subchronic toxic test (14-week), 55 female SD rats (age, 6 weeks) were divided
      randomly into 5 groups: control, low, medium, high and super high dosage,
      respectively, which drank water with TMT of 0, 8.20, 32.81, 131.25 and 262.50
      microg x kg(-1) x d(-1) for 14 weeks. Then serum K+ levels were measured; the
      activities of HK-ATPase (HKA) in kidneys were detected by the method of
      determinated phosphorus content; Western Blot assay and real-time PCR were used
      to exam the protein and mRNA expression levels of HKA in kidneys, respectively.
      RESULTS: The serum K+ level in super-high dosage group was (5.6 +/- 0.4) mmol/L,
      which was significantly lower than that [(6.9 +/- 0.3) mmol/L] in control group
      (P < 0.01). The HKA enzymatic activity of kidneys in low and super high dosage
      groups was 4.50 +/- 1.45 and 4.55 +/- 0.72 micromolPi x mg prot(-1)h(-1),
      respectively, which were significantly lower than that (6.55 +/- 0.77 micromol Pi
      x mg prot(-1) h(-1)) in control group (P < 0.05). CONCLUSION: When rats were
      exposed subchronic to TMT, the renal HKA activity could reduce, but the
      expression levels of HKA protein and mRNA did not decrease.

PMID- 21941787
TI  - [Analysis of developing feature of pneumoconiosis].
AB  - OBJECTIVE: To get the message about the developing feature of pneumoconiosis by
      analyzing the data from 353 cases of pneumoconiosis diagnosed in our hospital
      recent 6 years. METHODS: To analyze the onset age, onset service years and
      incubation period of 353 cases of pneumoconiosis, especially in silicosis, coal
      worker's pneumoconiosis and potter's pneumoconiosis. RESULTS: 353 patients
      referred to 10 species of pneumoconiosis, the silicosis, coal worker's
      pneumoconiosis and potter's pneumoconiosis were accounted for 28.90%, 43.34% and
      15.01% of total pneumoconiosis respectively. Diagnosed patients who began to
      exposed to dust during 1950's to 1980's accounted for 84.99% of all the diagnosed
      patients. The onset age, onset service years and incubation period of silicosis,
      coal worker's pneumoconiosis and potters pneumoconiosis all showed a shorten
      trend compared each other every decade, especially after 1980's, but excluded
      potter's pneumoconiosis because of that the ceramics industry switched to other
      products in Beijing. There was a positive correlation relationship between
      average onset age and incubation period in three main species of pneumoconiosis
      mentioned above, but no significant difference could be seen in average promotion
      years. Additionally, comparing with other type of work, jade machining workers
      showed such a characteristic as younger onset and short incubation period.
      CONCLUSION: The development situation of silicosis, coal worker's pneumoconiosis
      is still no so optimistic, and the strict surveillance and administration
      especially to the township enterprises with poor production conditions should get
      further strengthen.

PMID- 21941788
TI  - [A coal mine and coal preparation plant coal dust workplace present situation
      investigation and analysis].
AB  - OBJECTIVE: Through a detection of dust in the coal mines workplace, to understand
      the status of occupational hazards, and the evaluation of occupational hazards,
      provide subject to control occupational hazards. METHOD: According to production
      process and "hazardous substances in workplace air monitoring, sampling norms"
      and other standards to determine the sampling points and sampling of coal dust.
      RESULT: Underground mining operations in 21 subjects with time-weighted average
      concentration of dust types pass rate of 28.6%, of which five types of dust
      hazard grade II, six types of dust hazard rating of 0, and the remaining types of
      grade I dust hazard levels. Coal dust test six types of time-weighted average
      concentration of 83.3% pass rate, only one types of dust hazard grade I, all the
      rest is 0. Calculated by the detection of dust overrun 18 times operating sites,
      the pass rate of 72.2% results. CONCLUSION: Purified water spray and air flow
      curtain of dust control has played a certain role, but the work of underground
      working conditions and environmental constraints, most of the dust concentration
      in workplace occupational exposure limits do not meet the requirements,
      recommended the strengthening of dust or Dust the daily management and
      maintenance of equipment, strengthen the ventilation, personal protection
      officers to strengthen operations.

PMID- 21941789
TI  - [Current status and control of existed productive dust in a thermal power plant].

PMID- 21941790
TI  - [Clinical value of noninvasive intermittent positive-pressure ventilation in
      pneumoconiosis combined with respiratory failure].
AB  - OBJECTIVE: To evaluate the value of noninvasive intermittent positive-pressure
      ventilation (NIPPV) in treatment of patients with pneumoconiosis combined with
      respiratory failure. METHOD: Three were 46 inpatients with pneumoconiosis
      combined with respiratory failure. Twenty-six inpatients treated with
      conventional therapy and NIPPV were categorized as treatment group; Twenty
      inpatients just treated by conventional therapy served as control group. Compared
      with the changes of HR, RR and arterial blood gas index (PH, PaCO2, PaO2) in two
      groups after treatment. RESULTS: The effective ratio of treatment group was
      88.5%, control group was 60%, which had significant difference (P < 0.05); The HR
      in treatment group after treatment was (95.38 +/- 10.75) beats per minute,
      control group was [(103.00 +/- 12.56) beats per minute; The RR in treatment group
      was (21.69 +/- 1.37) breaths per minute, control group was [(22.60 +/- 1.57)
      breaths per minute]; The PaCO2 in treatment group was (52.88 +/- 10.75)mm Hg,
      control group was [(59.66 +/- 11.49)mm Hg]; All of those were significantly
      decreased than those in control group (P < 0.05). The PaO2 in treatment group was
      (100.77 +/- 25.3) mm Hg, control group was [(71.82 +/- 17.94) mmHg]; Compared
      with the control group, PaO2 in the treatment group increased significantly (P <
      0.05). CONCLUSION: NIPPV is beneficial to pneumoconiosis combined with
      respiratory failure in different degrees.

PMID- 21941791
TI  - [The value of P wave dispersion in the diagnostic of pulmonary heart disease in
      coal worker's pneumoconiosis].
AB  - OBJECTIVE: To determine the value of measuring P wave dispersion of ECG in the
      diagnosis of pulmonary heart disease in patients with coal worker's
      pneumoconiosis. METHODS: 50 patients with stage III and 185 patients with
      different stages of coal worker's pneumoconiosis were included in the study.
      Compare the P wave of ECG and investigate nine indexes of P-wave dispersion.
      RESULTS: The figure of ECG P wave dispersion was distinct, easy to measure and of
      high positive incidence. The positive incidence of indexes (P wave voltage > or =
      0.22 mV, P wave axis > or = +80 degrees, P1 lead peak angle < or = 70 degrees, P
      wave elevation speed > or = 0.5 mm/s, PavL inversion, IPIV1 > or = 0.03 mms, Ta
      wave depressed > or = 0.05 mV, height of PV1 biphasic wave straight sharp corner
      > 0.07 mV) were 74.00%, 72.00%, 68.00%, 62.00%, 56.00%, 60.00%, 54.00%, 34.00% in
      50 cases patients with stage III coal worker's pneumoconiosis, the discrepancy
      had statistical significance (P < 0.01). The above ECG P wave dispersion indexes
      was higher with coal worker pneumoconiosis stage, the discrepancy had statistical
      significance (P < 0.01). CONCLUSIONS: Adopt P wave dispersion as the index of
      measuring right atrial hypertrophy is beneficial to the early diagnosis of
      pulmonary heart disease in patients with coal worker's pneumoconiosis.

PMID- 21941792
TI  - [Application of cystostomy drainage make thoracic cavity close drainage on
      pneumoconiosis].

PMID- 21941793
TI  - [Analysis on 33 cases of secondary pulmonary fungal infections of
      pneumoconiosis].

PMID- 21941794
TI  - [Suppression subtractive hybridization technique and its applications in
      pulmonary fibrosis].

PMID- 21941795
TI  - A time for consensus.

PMID- 21941796
TI  - NMC criticised for advice on early referral of high-risk staff.

PMID- 21941797
TI  - Campaign aims to establish safer care for older people in hospitals.

PMID- 21941798
TI  - Major study shows nursing care benefits patients with depression..

PMID- 21941799
TI  - Nurses question practicality of revised hypertension guidance.

PMID- 21941800
TI  - Regulator under pressure to take tougher approach to revalidation.

PMID- 21941801
TI  - Open to temptation.
AB  - Some hard-to-reach patients behave more healthily in the short term if offered
      incentives such as shopping vouchers. Long term schemes are difficult to manage.

PMID- 21941802
TI  - A soldier's champion.
AB  - Betsi Cadwaladr overcame huge obstacles to nurse the sick in the Crimea.
      Camaignes hope to create a lasting memorial to her achievements.

PMID- 21941803
TI  - Making an emotive decision.
AB  - Only one in five women undergoing mastectomy for breast cancer in the UK have
      immediate breast reconstruction.

PMID- 21941804
TI  - Expecting company.
AB  - Pregnancy Pals and Birth Buddies is a community-based parent support project run
      by social enterprise Parents 1st.

PMID- 21941805
TI  - Understanding the NMC code of conduct: a student perspective.
AB  - The Code, published by the Nursing and Midwifery Council (NMC) (2008), provides
      standards of performance and ethics for nurses and midwives, and is a means of
      safeguarding the health and wellbeing of the public. Guidance from the NMC may
      appear relatively straightforward, however it can be difficult to implement in
      practice. This article identifies specific challenges that nurses may be
      presented with when adhering to The Code, as well as more general issues in
      interpreting the standards.

PMID- 21941806
TI  - Using solution-focused communication to support patients.
AB  - Nurses want to help patients; it is one of their main roles and a key source of
      job satisfaction. However, finding the time despite low staffing levels and a
      heavy workload is a constant challenge. This article provides an overview of
      solution-focused communication -an approach valued by an increasing number of
      nurses because of its brevity and effectiveness in empowering patients to find
      the solutions that will help them to deal with their health challenges.

PMID- 21941807
TI  - Preventing falls in older people: assessment and interventions.
AB  - Falls can have a devastating effect on older people. Physical injury and fear of
      further falls may restrict social and physical activities, leading to a lack of
      confidence and social isolation. Nurses need to assess patients who have fallen
      to identify injury as well as to instigate appropriate interventions to reduce
      the risk of further falls. This article provides an overview of the assessment
      tools and management strategies that can be used in daily practice, particularly
      in the community setting.

PMID- 21941808
TI  - Nebuliser therapy.

PMID- 21941809
TI  - Grounds for complaint.

PMID- 21941810
TI  - Give nurses a place at the table.

PMID- 21941811
TI  - A beacon of patient-centred care.

PMID- 21941812
TI  - The impressions we leave...

PMID- 21941813
TI  - Increased mortality among the critically ill patients admitted on weekends: a
      global trend.
AB  - Critical illness and injury have no concept of time and do not always occur
      within regular business hours or at times conducive to optimal hospital function.
      In fact, it is a global trend that critically ill patients admitted to hospitals
      on weekends suffer higher mortality rates than those admitted during the week.
      Using a Canadian nursing lens, it is clear that there are some obvious
      differences in hospital function on weekends that include decreased hospital
      staffing, access to diagnostic services, intensivist coverage and the reluctance
      of patients to seek care on weekends. However, the exact differences contributing
      to the increased mortality in this patient population on weekends and the
      solutions remain unclear in the literature, and further research is needed.
      Possible solutions include moving to a "closed" ICU system, increasing nurse
      staffing, intensivist coverage and diagnostic accessibility, and creating a true
      seven-day hospital system. Finally, it is unclear exactly how to solve the nurse
      staffing portion of this problem, as it appears internally linked to the nursing
      profession and externally to hospital management, recruiting difficulties and
      financial restraints, and a problem that will take more than change in nursing
      management strategy to resolve.

PMID- 21941814
TI  - Cerebrospinal fluid collection: a comparison of different collection sites on the
      external ventricular drain.
AB  - BACKGROUND: Intracranial pressure monitoring using an external ventricular
      drainage (EVD) system is the most commonly used technology to monitor
      intracranial pressure or drain cerebrospinal fluid (CSF) in neurological and
      neurosurgical patients. CSF samples are collected routinely from the EVD system
      for laboratory tests. No study has been conducted to identify where the most
      appropriate site for CSF collection is in order to reduce the disruption of the
      closed EVD system and reduce the risk of infection. PURPOSE: The purpose of this
      study was to identify a CSF sampling port in the EVD system that is easily
      accessible, provides accurate results, and minimizes disruption to the closed EVD
      system. SAMPLE: Fifty patients admitted to the neurological and neurosurgical
      intensive care step-down unit with the EVD system between July 2007 and September
      2009 agreed to participate in the study. There were 21 women and 29 men. Forty
      seven patients' data were analyzed. METHOD: The design was quasi-experimental
      using a convenience sample. Two samples of CSF were collected daily. One sample
      was collected from the proximal port and another sample was collected from the
      distal port. The second sample was collected immediately after the first. Each
      set of samples (proximal and distal) was tested and compared for any differences
      in appearance, culture results, and concentrations of protein, glucose, and white
      cell count. RESULTS: Using a two-tailed paired t test with 95% confidence
      interval, there was no statistically significant difference between the samples
      obtained from the two collection sites for protein, glucose, white cell count,
      appearance, and culture. Pearson's correlation coefficient was also used to
      analyze the correlation for the continuous measures. Both protein and glucose had
      very high correlations. However, the white cell count, and white cell counts and
      culture had very low correlations. CONCLUSION: The distal port of the EVD system
      is safe and easy for CSF collection. It also provides accurate results for CSF
      samples. When the CSF sample is collected from the distal port, the entire volume
      of CSF in the drip chamber should be collected and tested to obtain an accurate
      WBC count per unit of volume.

PMID- 21941816
TI  - [Within or beyond one's assumptions].

PMID- 21941815
TI  - Drug name alert: potential for confusion between pradax and plavix.
AB  - In this article, the authors highlight an incident that involved a mix-up between
      the oral anticoagulant medication Pradax (dabigatran etexilate) and the
      antiplatelet medication Plavix (clopidogrel). Because critical care nurses may
      admit or care for patients who are receiving (or have received) one of these
      medications, it is important that they be aware of the potential for confusion
      between these two drug names throughout the medication-use process.

PMID- 21941817
TI  - [Role of JSS in education for young surgeons].

PMID- 21941818
TI  - [Recent trend of rectal cancer surgery].

PMID- 21941819
TI  - [Endoscopic treatment for early rectal cancer].
AB  - Endoscopic treatment for early rectal cancer was investigated. The
      characteristics of early rectal cancer were compared with those of early colon
      cancer, and the advantages of endoscopic treatment were evaluated. The
      indications for endoscopic resection are mucosal cancer, slight submucosal
      invasion without vessel or lymphatic involvement, poorly differentiated
      adenocarcinoma, and sprouting. The presence of other characteristics indicates
      the need for surgical resection. Early rectal cancers in the form of laterally
      spreading tumors of the non-granular, pseudodepressed type should be treated with
      endoscopic submucosal dissection due to the high incidence of submucosal
      invasion. The decision on the procedure for the treatment of early rectal cancer
      may be complicated because of the anatomic character and function of the ano
      rectal area, complications of anal dysfunction, and incidence of leakage from the
      anastomosis after surgery. A precise diagnosis after endoscopic examination based
      on the pit pattern with magnifying endoscopy may be an effective aid in selecting
      the most appropriate endoscopic treatment for early rectal cancer.

PMID- 21941820
TI  - [Pros and cons of local excision procedures for early rectal cancer].
AB  - The most appropriate technique for local excision of early rectal cancer remains
      controversial. Surgeons are responsible for determining whether the intent of
      treatment is curative or palliative and which technique to employ. The aim of
      local excision is to perform full-thickness resection of early rectal cancer with
      sufficient surgical margins for pathologic study. Patients in whom lymph node
      metastasis is suspected should undergo additional surgery. Various procedures
      have been reported so far. Local excision techniques are currently most often
      performed via the transanal approach under direct visualization, which include
      conventional techniques and minimally invasive transanal surgery (MITAS), or
      transanal endoscopic microsurgery (TEM). MITAS and TEM provide access to more
      proximal tumors up to 20cm from the anal verge. While posterior approaches are
      useful to expose the rectal wall to facilitate local excision, these procedures
      are infrequently performed at present due to the significant associated
      morbidity, such as bowel fistulas and impaired anorectal function. In conclusion,
      it is essential to recognize the pros and cons of the various techniques when
      performing local excision for early rectal cancer.

PMID- 21941821
TI  - [Chemoradiation combined with total mesorectal excision for patients with locally
      advanced rectal cancer].
AB  - Rectal cancer is characterized by a high rate of local recurrence. Although it is
      widely believed that local control results in improved patient outcome, its
      strategy is still controversial. In Japan, total mesorectal excision (TME) or
      tumor-specific mesorectal excision (TSME) with pelvic sidewall dissection is
      regarded as the standard procedure, while TME or TSME with preoperative
      chemoradiotherapy (CRT) is common in Western countries. Most clinical data have
      indicated that preoperative CRT is not associated with improved long-term
      survival but with a lower incidence of local recurrence. In addition, CRT is
      known to enhance the severity of impaired sphincter function. Currently, trials
      using CRT regimens with newly developed chemotherapy agents are ongoing to
      elucidate the effect on the control of distant metastasis. According to clinical
      reports, the prognosis of Japanese patients undergoing surgery alone is as
      favorable as that in patients undergoing surgery plus CRT in the West, which
      implies that CRT is not a necessary treatment but a selective option. The precise
      prediction of tumor response and advances in CRT regimens resulting in better
      survival may improve the treatment of rectal cancer in the future.

PMID- 21941822
TI  - [Sphincter-saving resection for low rectal cancer].
AB  - R0 resection, preservation of the anal sphincter, and local control are
      considered to be the most important target criteria in rectal cancer surgery.
      Many efforts have been made in recent years to increase the rate of sphincter
      preservation by performing pull-through operations, ultra-low anterior resection
      (U-LAR), and intersphincteric resection (ISR). U-LAR is the standard surgery for
      patients with lower rectal cancer to preserve anal function. Reconstruction in U
      LAR is mainly performed using stapled anastomosis. Although conventional coloanal
      anastomosis makes it possible to preserve the anal sphincter, the mechanical
      methods are difficult. In that case, almost all the internal sphincter is
      preserved. The final options for preserving the sphincter are ISR and external
      sphincter resection (ESR). Although the internal sphincter is sacrificed
      partially, subtotally, or totally in ISR, and the external sphincter is resected
      partially or extensively in ESR, complete or incomplete anal function is
      maintained. However, the literature is not clear regarding long-term oncologic
      outcome and anal function after these procedures. The application of these
      surgical techniques can reduce the rate of abdominoperineal resection in very low
      rectal cancer. The indications for these procedures must be carefully determined
      based on tumor site and stage as well as the patient's own preference.

PMID- 21941823
TI  - [Treatment of lateral node metastasis from lower rectal cancer].
AB  - Lateral lymphatics of the rectum originate in the area where branches of the
      inferior hypogastric plexus and the middle rectal vessels from the internal iliac
      vessels enter the mesorectum below the level of the peritoneal reflection in the
      pelvis, then reach the bifurcation of iliac vessels along the internal iliac
      vessels. Among lateral lymph nodes, the middle rectal, obturator, and internal
      iliac lymph nodes are important from the viewpoint of both the incidence of
      metastais and treatment effects. Although total mesorectal excision (TME) had
      become the standard surgical treatment for rectal cancer by the 1990s, this
      technique does not treat lateral node metastasis. A randomized clinical trial of
      TME versus D3 lymphadenectomy (JCOG0212) was started in 2003, and the
      registration of 701 patients with lower rectal cancer was completed in August
      2010. The results of this clinical trial are highly anticipated. In Japan, where
      the rate of local recurrence after surgery is low, patients at high risk of local
      recurrence such as those with lateral node metastasis, T4 disease, and multiple
      lymph node metastases in the mesorectum should be selected to receive
      preoperative chemoradiation. Japanese surgeons who treat rectal cancers are in an
      advantageous position because they have the additional measure of lateral node
      dissection along with TME and chemoradiotherapy.

PMID- 21941824
TI  - [Laparoscopic surgery for rectal cancer].
AB  - Although laparoscopic colon cancer surgery is widely accepted as a feasible
      alternative to open surgery, there is still limited evidence on the use of the
      laparoscopic approach for rectal cancer. Although laparoscopic rectal surgery is
      a technically demanding procedure with a steep learning curve because of
      adherence to the oncologic principle of total mesorectal excision, the
      laparoscopic approach has some advantages over open surgery, including not only
      less invasiveness but also a good surgical view of the deep pelvis through its
      magnification effect. At this time, information is still lacking on the long-term
      outcomes and efficicacy of laparoscopic rectal cancer surgery based on large
      scale, randomized, controlled trials, and many clinical guidelines recommend that
      laparoscopic rectal cancer surgery should only be performed with expertise under
      a clinical trial setting. Nationwide surveys show the numbers of laparoscopic
      rectal cancer surgery cases are increasing in Japan, and about 20% of rectal
      cancer operations are performed laparoscopically, but concerns about the
      concurrently increasing anastomotic leakage rate should be noted. The development
      of laparoscopic instruments specifically to facilitate dissection and transection
      of the rectum in the deep pelvis is expected to increase the future widespread
      adoption of this procedure.

PMID- 21941825
TI  - [Local treatment other than surgery for small size malignancy].

PMID- 21941826
TI  - [Current status and perspective of heavy-ion radiotherapy].

PMID- 21941827
TI  - [What we can learn from a case of medical malpractice--an inpatient with suicidal
      potential: issues regarding the clinical predictability].

PMID- 21941828
TI  - [Implantation technique for left ventricular assist device].

PMID- 21941829
TI  - [Japanese women surgeons' present and future: report of a survey on support
      environment and activities at facilities staffed with Japanese Surgical Society
      counselors].

PMID- 21941830
TI  - [Working for Japanese NP/PA after the great Tohoku natural disaster--talent of
      NP/PA on perspective of nurse].

PMID- 21941831
TI  - [Peculiar history to formation of 'Freely recuperate zone' in the National
      Sanatorium Kuryu Rakusen-en, Gunma, Japan (relation between the 'Old Yunosawa
      ward' and 'Freely recuperate zone' in the National Sanatorium Kuryu Rakusen-en)].
AB  - Hansen's disease sufferers had been visiting the hot spring, Kusatsu-Spa, in
      Gunma, Japan, for Toji (which means 'hot springs treatment' in Japanese) since
      the middle ages, as it was known reportedly for a long time to be effective in
      curing the disease. In 1869, Kusatsu-Spa was hit by a massive fire. The
      innkeepers, who suffered devastating damages, were trying to reconstruct the
      economy quickly by promoting the medical benefits of the hot spring. This made
      many Hansen's disease patients to visit and of which many stayed on a long term
      bases. They would use the hot spring with ordinary visitors. And, they had
      received the treatment of the spotted moxa cautery with the hot-spring treatment.
      Later on, Kusatsu- Spa became well known throughout Japan and as the numbers of
      ordinary visitors increased, they voiced their concerns in sharing the hot spring
      with the Hansen's disease patients. Therefore, the innkeepers decided to move the
      patients to another district called Yunosawa and suggested to make a special
      village of just the patients. In 1887, the representative of the patients came to
      an agreement with the mayor of Yunosawa to establish a treatment centre there.
      Yunosawa became part of an administrative area of Kusatsu Town. The area seemed
      to become a local-governing area mainly shaped by Hansen's disease sufferers and
      the first legal residential area where Hansen's disease sufferers were given
      citizenships and may convalesce freely. However, in 1931, leprosy prevention law
      was passed, and the Japanese government built a new medical treatment centre of
      Hansen's disease, 4km away from Kusatsu- Spa, which is called National Sanatorium
      Kuryu Rakusen-en. After deliberations with the representative of the Hansen's
      disease patients living in the Yunosawa area and the governor of Gunma
      Prefecture, who received the order from the Japanese government to move them, had
      agreed to the mass relocation in 1941. This is how Yunosawa had closed its 55
      years history and many Hansen's disease patients had moved to the National
      Sanatorium Kuryu Rakusen-en. The 'Freely recuperate Zone' within the centre
      houses affluent patients who had enough funds to build their own houses. I was
      able to hear from many residential People who have historical knowledge of the
      above and would like to report it here.

PMID- 21941832
TI  - [Leprosy outpatient clinic in Aichi Prefecture, Japan].
AB  - Until the Japanese Leprosy Prevention Law was abolished in 1996, leprosy
      patients, regardless of their severity, had to be treated by accredited doctors.
      The majority of them had to be confined in a sanatorium to be treated, since only
      few hospitals/sanatoria had outpatient clinics for leprosy patients. This de
      facto confinement limited their occupational, social, financial, and family
      options, but no clear criteria/guidelines allowing discharge existed. The
      importance of leprosy outpatient clinics was almost never debated until 1962,
      when Tofu Association (a foundation established in 1952 to support the confined
      patients) and the National Suruga Sanatorium planned the opening of the clinic.
      This clinic looked after total of 4,977 patients until the abolishment of the
      Law. Since 1996, 349 persons consulted the clinic as of 2010. The importance of
      the continuation of these clinics is beyond dispute, even in low-endemic
      countries. However, the diminishing number of patients and demands in this
      country makes the management difficult. Thus, coordination with the local clinics
      and dermatologists is inevitable.

PMID- 21941833
TI  - [Histopathological examination of Buruli ulcer (Mycobacterium ulcerans disease)
      in surgically removed skin].
AB  - We report the results of an examination of gross images of two patients with
      Buruli ulcer and a histopathological evaluation of surgically removed skin from
      two other cases at the non-ulcerated and ulcerated stages, respectively.
      Histopathologically, dermal nodes were found in the non-ulcerated specimen; while
      wide necrosis of skin and fibrin deposition, as well as Langhans giant cell,
      epitheloid cells, and vasculitis, were observed in the ulcerated specimen, with
      granuloma in the lymph nodes. M. ulcerans was positive in a Fite stain and in a
      PGL-1 immunohistological stain. Based on these cases, we discuss the histological
      characteristics of Buruli ulcer.

PMID- 21941834
TI  - [Japanese guideline on thalidomide usage in the management of erythema nodosum
      leprosum].
AB  - Treatment of erythema nodosum leprosum (ENL, type 2 reaction) using thalidomide
      provides effective alternative choice to steroid therapy. Yet, the Japanese
      National Health Insurance approves thalidomide prescription only for the
      treatment of multiple myeloma under the Thalidomide Education and Risk Management
      System (TERMS). Benefit of thalidomide therapy for patients with ENL is already
      an established fact based on various reports from other countries, but limited
      experiences and standards in Japan have hindered application of the medication to
      our patients. This led us to compose a local guideline. Based on and following
      the TERMS, we suggest starting thalidomide from 50-100 mg/day and then onwards
      adjusting the dose according to the symptoms of each patient, not to exceed the
      maximum recommended dose of 300 mg/day, for the treatment of ENL.

PMID- 21941835
TI  - [Our role in sentinel surveillance for drug resistance in leprosy by global
      leprosy programme].
AB  - Sentinel surveillance for drug resistance in leprosy by global leprosy programme
      has launched in 2006. Possible contribution of Japanese researchers to global
      leprosy control in the future were discussed on the base of circumstances of the
      project and our assignment in the sueveillance.

PMID- 21941836
TI  - [Practice of international collaborations in Southeast Asia].
AB  - Leprosy Research Center is engaged in the international collaborative research
      project since 1989. The project was consists of two parts. One part is the JICA
      training course which has been practiced since 1989. Another part is the
      international collaborative research which was started in Indonesia in the year
      1991. Author has participated in this project since 1998. Then, we started
      collaboration with various organizations including Pakistan, Vietnam, and
      Myanmar. The contents of the collaborative research were mainly technical
      assistances for leprosy diagnosis and we have trained young doctors, staff to
      conduct serological diagnosis and molecular biological diagnosis of leprosy. The
      projects between the countries were succesful. Throughout the collaboration with
      foreign countries, author felt strongly that one of most important things in such
      collaboration was better communication and relation between people having
      different cultural background.

PMID- 21941837
TI  - [What it means to be "infected"--how a human body, or health professionals combat
      "infection"].
AB  - Human immunology and relationship between immune mechanism and infection were
      explained. Humoral immunity and cellular immunity collaborate properly and
      eliminate microorganisms. In immunocompromised host these mechanisms are broken.
      For prevention of healthcare associated infections, standard precausion is
      important basically. Additionary, according to the status of the patient, contact
      precaution, droplet precaution or airborne precaution should be applied.

PMID- 21941838
TI  - [Caring for children's "mind" after the earthquake].

PMID- 21941840
TI  - [Preliminary evidence of neurobiological and behavioral consequences of exposure
      to childhood maltreatment on regional brain development].
AB  - In recent years, the topic of child abuse as an issue facing Japanese society has
      gained considerable attention with regard to the field of medicine and education
      and also in scenarios that relate to child care. The definition of child abuse
      includes abusing children verbally or psychologically, and is not limited to
      abusing children physically such as beating, sexual abuse, or neglect. Recent
      studies have revealed that emotional trauma during childhood development could be
      much more difficult to treat than physical abuse. Severe abuse during childhood
      can cause abnormal brain development and have a negative impact later in life. In
      this review, I will introduce the mechanisms of brain damage due to child abuse
      with consideration of how and when child abuse can have an impact on the victims'
      brains. The information presented is based on a collaborative study with the
      Psychiatry Department at Harvard University on the relationship between brain
      functions and the human mind.

PMID- 21941839
TI  - [Three-year-old boy presenting with psychomotor retardation and choreoathetosis].

PMID- 21941841
TI  - [Neurotransmitter disorders in children--special reference to Segawa disease].
AB  - Aminergic neurotransmitter disorders occurring in childhood include metabolic
      disorders of pteridine and tyrosine hydroxylase (TH). Pteridine metabolic
      disorders cause a deficiency of serotonin (5-HT) and dopamine (DA) and TH
      disorder causes a deficiency of noradrenaline (NA) and DA in the terminals of
      each aminergic neuron. The activities of TH or DA in the terminals are marked in
      early childhood, and then they show an exponential age-dependent decrement and
      achieve stationary or minimal levels in the twenties. As observed in Segawa
      disease, TH or DA activities in these disorders follow this age-related decrease
      with levels around 20% of normal, and patients develop symptoms age-dependently,
      with onset in childhood, progression by the late teens, and a stationary period
      after the twenties, but this does not cause morphological changes. These
      phenomena may occur with other neurotransmitters. So replacement therapies are
      effective irrespective of the clinical course. However, early-onset cases in
      infancy or early childhood showing a marked decrement of 5-HT or NA activities
      show postural hypotonia and failed locomotion. These cause failure in atonia
      restriction in the REM stage and induce dysfunction of the pedunculopontine
      nucleus, and, consequently induce dysfunction or failure in the development of DA
      neurons in the sutbstantia nigra and ventrotegmental area. These relate to
      failure in the development of higher cortical functions. Thus, assessing of ages
      at onset and activities of antigravity muscles and locomotion in infancy is
      cardinal for the treatment the neurotransmitter disorders occurring in infancy
      and early childhood. PARK2 with deficiency of DA in the substantia nigra leads to
      dystonia in the teens and Parkinson disease after 20 years, although these
      respond to 1-Dopa favorably but induce D2 receptor upregulation and intractable
      dyskinesia. A decrease of DA in the perikaryon leads to symptoms after 10 years
      and causes dysfunction of the target structures.

PMID- 21941842
TI  - [Clinical features of Japanese pediatric patients with anti-aquaporin 4
      antibody].
AB  - Recently, a disease-specific antibody was found in serum from patients with
      neuromyelitis optica (NMO), and its target antigen was identified as aquaporin 4
      (AQP4) water channel protein. There is no clinical picture of pediatric cases
      with anti-AQP4 antibody, except one report from North America. Here, we report
      the clinical features of 18 Japanese anti-AQP4-antibody-positive patients with
      childhood-onset of NMO. Of the 2000 patients who had been examined for anti-AQP4
      antibody at Tohoku University Hospital up until 2008, 60 were under 15 years of
      age at onset, and 18 of them were positive for anti-AQP4 antibody. We analyzed
      the clinical information on those patients. There were 14 girls and 4 boys (M:F
      ratio = 1:3.5). The age of onset ranged from 3 to 15 years old (median 13). The
      clinical diagnoses of the 18 patients before the anti-AQP4 antibody tests were:
      NMO in 8 (44%), MS in 7 (39%), and opticospinal MS (OSMS) in 3 (17%). Nine
      patients developed only optic neuritis at onset. At the last follow-up, brain
      magnetic resonance imaging (MRI) was abnormal in 14 patients, nine had monocular
      or binocular blindness, and the expanded disability status scale score was 6.0 or
      higher (cannot walk without support) in eight patients. NMO has a poor prognosis,
      as seen in adult cases, suggesting the importance of an early diagnosis using the
      anti-AQP4 antibody test to institute effective immunosuppressive treatment.

PMID- 21941843
TI  - [Children with attention deficit/hyperactivity disorder and pervasive
      developmental disorder:attention and response inhibition in the kiddie continuous
      performance test].
AB  - Continuous Performance Test (CPT) is widely used to assess the attention function
      and response inhibition in both children and adults. This study attempts to
      examine the performances of boys with attention deficit/hyperactivity disorder
      (AD/HD) and pervasive developmental disorder (PDD) with and without comorbid
      AD/HD using a CPT. Among the various versions of the CPT available, we used the
      Kiddie CPT (K-CPT) modified for younger children. The K-CPT was administered to
      children with AD/HD (n=22), those with PDD (n=19), and typically developing
      children (n=41) from 7 to 12 years of age. All children were drug free at the
      time of examination. The performances were examined in 6 measures:total number of
      omission errors (OE), total number of commission errors (CE), mean hit reaction
      time (HRT), hit reaction time standard error (HRTSE), perceptual sensitivity
      (d'), and response style (beta). Significantly lower scores in d' and a tendency
      to more errors in CE were found in the AD/HD group compared with the control
      group. Significantly lower scores in d' and significantly more errors in CE were
      also found in the PDD group with AD/HD symptoms compared with the control group.
      Moreover the AD/HD group showed significantly more errors in OE and higher scores
      in HRTSE compared with the control group. There were no significant group
      differences between the PDD group without AD/HD symptoms and the control group on
      all measures. Less favorable scores in AD/HD suggest inadequate selective
      attention, sustained attention and/or response inhibition. Results of the PDD
      group with comorbid AD/HD may reflect a basis of AD/HD impairment. Our findings
      may provide an understanding of neuropsychological characteristics underlying
      developmental disorders.

PMID- 21941844
TI  - [Three children with Rasmussen encephalitis showing marked improvement in daily
      life activity following the functional hemispherectomy].
AB  - We investigated seizure, intelligence quotient (IQ), and neurological outcomes
      including the process of motor function recovery after functional right
      hemispherectomy in 3 children with Rasmussen's encephalitis (RE). Before the
      procedure, they were unable to walk, nor sit without support due to progressive
      worsening of left hemiplegia and relentless epilepsia partialis continua (EPC) of
      the left extremities, which were refractory to antiepileptic drug and
      immunological treatment. After functional right hemispherectomy, EPC completely
      disappeared, although complete left hemiplegia was sustained. However, they
      recovered up to being able to walk independently with assistance devices, and to
      have an ordinary life with family support within 1.5 to 5 months through
      rehabilitation. At the same time, the interictal EEG improved on the unaffected
      side of hemisphere, exhibiting a posterior alpha rhythm. Their IQ also improved,
      and they were able to attend school. Early functional hemispherectomy should be
      considered before patients with RE are left in a serious condition due to
      progressive worsening of hemiplegia and seizures refractory to the available
      treatment.

PMID- 21941845
TI  - [Neuropsychological profile of children with cryptogenic localization-related
      epilepsy and its association with age at onset].
AB  - The aim of this study was to investigate the neuropsychological profile of
      children with cryptogenic localization-related epilepsy (CLRE).
      Neuropsychological evaluations were performed in 16 CLRE children and 14 children
      with idiopathic localization-related epilepsy (ILRE) for control within 8 months
      (average 2.1 months) of initial seizure. The neuropsychological tests used in
      this study are as follows: the Wechsler Intelligence Scale for Children-Third
      Edition, Wechsler Intelligence Scale for Children-Revised, and Wechsler Preschool
      and Primary Scale of Intelligence. Age at onset and test differed significantly
      between CLRE and ILRE, while the duration between onset and test and the number
      of seizures before test did not. No marked difference was observed in the
      neuropsychological profile between 2 groups; however, the discrepancy between VIQ
      and PIQ was significantly larger in CLRE than in ILRE. This discrepancy was
      negatively correlated with age at the time of seizure onset (r = -0.615, and p =
      0.011). The laterality in discrepancy between VIQ and PIQ was associated with the
      dominance of interictal discharge. In conclusion, children with lower age at the
      time of seizure onset were likely to have had a larger discrepancy between VIQ
      and PIQ.

PMID- 21941846
TI  - [Reading aloud as rehabilitation method for children with dyslexia detected at
      the first grade in their primary school].
AB  - We provided reading aloud instructions to a child who was diagnosed with dyslexia
      in a regular class of 69 first graders, comprising 33 boys and 36 girls, during a
      test of reading sentences aloud. The instructions consisted of a 2-step approach,
      i.e., decoding instruction and vocabulary instruction. First, a decoding
      instruction, which emphasized an important point in effortless decoding, was
      presented to the child. Next, a vocabulary instruction, which aimed to facilitate
      word-form recognition, was provided. We found that, the decoding instruction was
      effective in decreasing the number of reading errors, and that the vocabulary
      instruction was effective against reducing the time taken to read aloud.

PMID- 21941847
TI  - [Successful plasma exchange treatment for a case with neuromyelitis optica].
AB  - We report a 13-year-old girl diagnosed with neuromyelitis optica (NMO). We also
      report that plasma exchange could be performed early in her clinical course as
      well as her good response to this treatment. At the onset, transient numbness of
      both upper extremities appeared. Approximately one month thereafter, photesthesia
      of the left eye disappeared and she visited our hospital. Optic neuritis and
      myelitis were diagnosed based on neuroimaging of the brain and spinal MRI scans.
      Intravenous high-dose methylprednisolone was administered. Subsequently, although
      left vision improved to 0.4, numbness of the hands and feet appeared during
      methylprednisolone therapy. Since anti-AQP-4 antibody seropositivity was
      confirmed after methylprednisolone therapy, she met the NMO diagnostic criteria.
      Therefore, plasma exchange was performed followed by high dose methylprednisolone
      therapy, which improved left vision to 0.8 and the sensory disturbance of the
      hands and feet disappeared. A 0.5 mg/kg/day dose of prednisolone was then
      administered prophylactically, followed by plasma exchange, and there has been no
      relapse to date. In general, the rate of NMO recurrence is high and the
      neurological prognosis is poor. Therefore, it is important to measure serum anti
      AQP4 antibody during the first attack, if NMO is suspected, because this value is
      useful for the diagnosis of NMO. Appropriate treatments including plasma exchange
      and prophylactic therapy should be started after confirming the diagnosis.

PMID- 21941848
TI  - [Future directions of pharmacogenomics (PGx)].
AB  - The factors for the individual differences include both genetic and environmental
      factors. Genome-wide association study (GWAS) was first developed in RIKEN in
      2002 and has now become a major research technology. In GWAS, the associations
      between genomic variations and the variations in the traits are analyzed by
      statistical genetics. As many as 100,000-2,500,000 polymorphic loci are
      distributed over the whole genome, and the associations between either genotypes
      or alleles and the phenotypes are analyzed. The phenotypes are either diseases,
      physical data or clinical laboratory data, and it was found that the targets of
      the available drugs are often included in the genes that were found to be
      associated with the diseases. These data indicate that the results from GWAS may
      be applied to the development of new drugs (GWDD; genome-wide drug discovery).
      GWAS started to influence pharmacogenomics in which the associations between
      genomic variations and drug reactions are studied. Genes associated with statin
      induced severe muscle damage, efficacy of interferon for C-type hepatitis,
      ribavirin-induced hemolytic anemia and carbamazepine-induced severe skin eruption
      were found by GWAS. In 2010, "Guidelines for clinical studies and tests in which
      pharmacogenomics is applied" was released as a draft.

PMID- 21941849
TI  - [Genome-wide association analyses for neuroleptic-induced tardive dyskinesia].
AB  - Tardive dyskinesia (TD) is characterized by repetitive, involuntary, purposeless
      movements that develop in patients treated with long-term dopaminergic
      antagonists, usually antipsychotics. By a genome-wide association screening of TD
      in 50 Japanese schizophrenia patients with treatment-resistant TD and 50 Japanese
      schizophrenia patients without TD (non-TD group) and subsequent confirmation in
      independent samples of 36 treatment-resistant TD and 136 non-TD subjects, we
      identified an association of SNPs in the HSPG2 (heparan sulfate proteoglycan 2,
      perlecan) gene with TD. By canonical pathway-based analyses with Ingenuity
      Pathway Analysis software, we also found that genes involved in the GABA receptor
      signaling pathway were significantly enriched among the genes with gene-based
      corrected association allelic P values of less than 0.05. The gene expression
      levels in the postmortem prefrontal brains in those with the risk genotypes for
      TD were in the opposite direction to those in mouse brains after long-term
      admiration of haloperidol. These findings indicate that individuals with the
      susceptibility to TD may have less ability to adapt to long-term exposure of
      neuroleptics in some gene expression levels.

PMID- 21941850
TI  - [Pharmacogenetics focused on special phenotypes].
AB  - It is well-known that the patients with autosomal recessive juvenile Parkinsonism
      (ARJP), which is caused by the loss of function mutation in the Parkin gene,
      often show psychiatric symptoms such as depression, paranoia, psychosis, panic
      attacks, anorexia nervosa or suicide attempts. The recently established syndrome,
      dopamine dysregulation syndrome (DDS), is also frequently observed in the
      patients with ARJP. These facts might indicate that immature personality, which
      leads to reactive depression, anxiety, or suicide attempt, and vulnerability of
      reward system in ARJP, which leads to DDS, are due to loss of function of the
      Parkin gene product. The present status of molecular genetic studies on other
      special adverse effects of psychotropic medicines such as hyperammonemia due to
      valproate and malignant syndrome by antipsychotics was additionally reported.

PMID- 21941851
TI  - [Development of a Guideline on Clinical investigation of Medicinal Product in the
      Treatment of Depression in Japan].
AB  - Drug development is one of the methods for qualitative improvement of medical
      treatment. The Ministry of Health, Labour and Welfare in Japan (MHLW) published
      "A Guideline on Clinical Investigation of Medicinal Product in the Treatment of
      Depression" in November 2010. The guideline was developed by a Japanese expert
      working group in psychiatry and regulatory science. The purpose of the guideline
      is to describe accepted principles and practices in the conduct of both
      individual clinical trials and development strategy for new medicinal products
      intended to be used for treating depression and to facilitate efficient drug
      development. This document describes the major issues discussed during the
      guideline development. This work was supported by Grants-in-Aid from the Research
      Committee of "A Guideline on Clinical Investigation of Medicinal Product in the
      Treatment of Depression", MHLW.

PMID- 21941852
TI  - [Expectation for future development of antidepressant based on the newly
      published guideline focusing on clinical evaluation of antidepressants].
AB  - The guideline to evaluate clinical response to antidepressants was newly
      published on November 16, 2010, in Japan, and provides useful suggestions in the
      development of new antidepressants. In this paper, the background of the
      establishment of the guideline and a perspective for the future development of
      antidepressants are described from a personal viewpoint.

PMID- 21941853
TI  - [Current and future views from pharmaceutical industry perspectives on
      development of antidepressants].
AB  - It has recently become possible to conduct placebo-controlled clinical studies in
      Japan. However, worldwide, there has been much discussion of the problems in
      placebo-controlled studies, such as the fact that the increase in the placebo
      response in clinical studies in depression increases the risk of failed studies
      and the number of patients that need to be enrolled. Japan has been participating
      in more multinational studies aimed at obtaining simultaneous worldwide approval.
      This paper discusses an overview of the development of antidepressants and
      examples of research that has been conducted on the placebo response, and
      describes the controversy regarding the designs of future studies as well as the
      issues involved in Japanese participation in multinational studies.

PMID- 21941855
TI  - APN regulatory changes taking effect.

PMID- 21941856
TI  - Colorado nurse knows the art of negotiation.

PMID- 21941854
TI  - Selective downregulation of N-methyl-D-aspartate receptor (NMDAR) rather than non
      NMDAR subunits in ipsilateral cerebral hemispheres in rats with middle cerebral
      artery occlusion.
AB  - Ischemic brain damage is believed to involve the drastic increase in
      extracellular glutamate levels after reperfusion and subsequent overactivation of
      both N-methyl-D-aspartate (NMDA) receptor (NMDAR) and non-NMDAR channels for
      delayed neuronal cell death mediated by Ca2+ overload. In this study, we
      evaluated expression profiles of mRNA and corresponding proteins for different
      subunits of NMDAR and non-NMDAR in brains of rats with transient middle cerebral
      artery occlusion (MCAO). Cellular vitality was markedly reduced in proportion to
      increasing durations of MCAO for 1 to 8 h when determined 1 day after
      reperfusion. Within 7 days after reperfusion, MCAO for 2 h led to a gradual
      decrease in the neuronal marker microtubules-associated protein-2 (MAP2) level in
      the ipsilateral cerebral hemisphere, in addition to inducing a transient increase
      in the microglial marker CD11b expression without affecting the astroglial marker
      protein levels. MCAO for 2 h significantly decreased the expression of both mRNA
      and corresponding proteins for NR1, NR2A and NR2B subunits of NMDAR, but not for
      non-NMDAR subunits, in the ipsilateral hemisphere. These results suggest that
      NMDAR may be preferentially down-regulated in response to ischemic signal inputs
      amongst three different subtypes of ionotropic glutamate receptors in rats with
      MCAO.

PMID- 21941857
TI  - Colorado becomes the 16th state to opt out of the Medicare physician supervision
      requirement for nurse anesthetists.

PMID- 21941858
TI  - Influenza immunization policies and nursing concerns.

PMID- 21941859
TI  - The demographic challenges facing Colorado's health care workforce.

PMID- 21941860
TI  - Healthcare financing: seeking better solutions.

PMID- 21941861
TI  - Have you ever felt like you were at your "limits"?

PMID- 21941862
TI  - Survey says: nurses' influence on health care is untapped.

PMID- 21941863
TI  - Taking beginning steps.

PMID- 21941864
TI  - The nursing and health care workforce in Colorado: driver of prosperity or an
      economic roadblock.

PMID- 21941865
TI  - Denis F. Kinane, BDS, PhD. A conversation with the new dean of Penn Dental
      Medicine.

PMID- 21941866
TI  - Serving the underserved: externships take students far afield for learning,
      service opportunities.

PMID- 21941867
TI  - Engaging globally.

PMID- 21941868
TI  - A lasting legacy to advanced training, care in oral and maxillofacial surgery.

PMID- 21941869
TI  - American Recovery and Reinvestment Act: a stimulus for research.

PMID- 21941870
TI  - A call to serve.

PMID- 21941871
TI  - Dental auxiliary utilization: creating hands-on clinical experiences for all
      students.

PMID- 21941872
TI  - Dana Graves, DDS, DMSc: bridging the gap between the clinic laboratory.

PMID- 21941873
TI  - Facilities update: new spaces, new technologies.

PMID- 21941874
TI  - What's in a word (label, phrase,term, etc.)?

PMID- 21941875
TI  - Inquiry-based science instruction and performance literacy for students who are
      deaf or hard of hearing.
AB  - Deaf and hard of hearing students, who cannot successfully access and utilize
      information in print, experience various difficulties in conventional science
      instruction, which heavily relies on lectures and textbooks. The purpose of the
      present review is threefold. First, an overview of inquiry-based science
      instruction reform, including the so-ciohistorical forces behind the movement, is
      presented. Then, the author examines the empirical research on science education
      for students who are deaf or hard of hearing from the 1970s to the present and
      identifies and rates inquiry-based practice. After discussing the difficulty of
      using science texts with deaf and hard of hearing students, the author introduces
      a conceptual framework that integrates inquiry-based instruction and the
      construct of performance literacy. She suggests that this integration should
      enable students who are deaf or hard of hearing to access the general education
      curriculum.

PMID- 21941876
TI  - Test item linguistic complexity and assessments for deaf students.
AB  - Linguistic complexity of test items is one test format element that has been
      studied in the context of struggling readers and their participation in paper-and
      pencil tests. The present article presents findings from an exploratory study on
      the potential relationship between linguistic complexity and test performance for
      deaf readers. A total of 64 students completed 52 multiple-choice items, 32 in
      mathematics and 20 in reading. These items were coded for linguistic complexity
      components of vocabulary, syntax, and discourse. Mathematics items had higher
      linguistic complexity ratings than reading items, but there were no significant
      relationships between item linguistic complexity scores and student performance
      on the test items. The discussion addresses issues related to the subject area,
      student proficiency levels in the test content, factors to look for in
      determining a "linguistic complexity effect," and areas for further research in
      test item development and deaf students.

PMID- 21941877
TI  - Representations of deaf characters in children's picture books.
AB  - Picture books can influence how children perceive people of different
      backgrounds, including people with disabilities whose cultures differ from their
      own. Researchers have examined the portrayal of multicultural characters with
      disabilities in children's literature. However, few have specifically considered
      the portrayal of deaf characters, despite increased inclusion of deaf characters
      in children's literature over the past two decades. The present study analyzed
      the portrayal of deaf characters in picture books for children ages 4-8 years. A
      content analysis of 20 children's picture books was conducted in which the books
      were analyzed for messages linked to pathological and cultural categories.
      Results indicated that these books did not portray Deaf characters from a
      cultural perspective but, rather, highlighted aspects of deafness as a medical
      condition, one that requires fixing and that perpetuates stereotypes of deafness
      as a disability.

PMID- 21941878
TI  - The effects of captions on deaf students' content comprehension, cognitive load,
      and motivation in online learning.
AB  - The authors examined the effects of captions on deaf students' content
      comprehension, cognitive load, and motivation in online learning. The
      participants in the study were 62 deaf adult students who had limited reading
      comprehension skills and used sign language as a first language. Participants
      were randomly assigned to either the control group or the experimental group. The
      independent variable was the presence of captions, and the dependent variables
      were content comprehension, cognitive load, and motivation. The study applied a
      posttest-only control group design. The results of the experiment indicated a
      significant difference (t = -2.16, p < .05) in content comprehension but no
      statistically significant difference in cognitive load and motivation between the
      two groups. These results led to suggestions for improvements in learning
      materials for deaf individuals.

PMID- 21941879
TI  - Deaf parents and pediatric cochlear implantation: an exploration of the decision
      making process.
AB  - The study examined factors in deaf parents' decision between cochlear
      implantation (CI) and traditional hearing aids for their child. The subjects were
      6 Flemish children ages 5-9 years with severe/profound congenital hearing loss,
      with at least 1 deaf parent. The researchers, who conducted thematic content
      analysis of qualitative data collected through parent interviews, found that with
      the exception of a family with 1 hearing parent, parents gave priority to Deaf
      identity, sign language, and ethical issues in deciding between CI and hearing
      aids. Medical risks were also mentioned. The researchers conclude that the
      decision-making processes of the parents involved factors that have also been
      found among hearing parents, as well as aspects that have not been reported to
      play a role in hearing parents' decision making. A further conclusion is that
      deaf parents' perspective merits attention in professional practice and empirical
      research.

PMID- 21941880
TI  - The role of counselors serving deaf or hard of hearing students in public
      schools.
AB  - Since enactment of Public Law 94-142, residential schools for d/Deaf or hard of
      hearing (d/Dhh) students have lost enrollment to public schools. Public school
      counselors now must meet d/Dhh students' counseling needs. There is little
      literature on if and how counselors are doing this. The present study used a
      survey to evaluate the job satisfaction and expectations of 22 counselors working
      with d/Dhh students in programs across the United States. Follow-up interviews
      were conducted with 6 participants functioning as counselors for d/Dhh students.
      Results indicated that the counselors were generally pleased with their role,
      which, however, diverged markedly from the American School Counselor Association
      (2003) national model. The interviews revealed 5 themes that may be unique to
      counselors serving d/Dhh students in public schools: Authority Based on
      Experience, Director

PMID- 21941881
TI  - Analysis of car-3-en-5-hydroperoxide.
AB  - HRGC-MS, using split/splitless injection (230 degrees C), showed that a
      dioxygenase from Pleurotus sapidus regio-selectively transformed (+)-car-3-ene to
      car-3-en-5-one as the major volatile product to minor amounts of the
      corresponding alcohol, and to some other volatiles. Thus, the reaction was
      assumed to be radical mediated and similar to the lipoxygenase catalyzed
      peroxidation of polyunsaturated fatty acids, but the expected car-3-ene
      hydroperoxides were not detected. TLC of the reaction products, followed by
      hydroperoxide specific staining, visually indicated the presence of
      hydroperoxides. TLC spots were eluted and re-analyzed using cool on-column
      injection, but only tailing peaks showing a mixed mass spectrum of car-3-en-5
      ol/one were obtained. An unequivocal identification of car-3-en-5-hydroperoxides
      was achieved only after using APCI(+)-LC-MS. Upon structural confirmation, the
      car-3-en-5-hydroperoxide was accumulated by preparative HPLC, re-injected cool on
      column, and the continuing degradation of the hydroperoxide to monoterpene ketone
      and alcohol during chromatography was verified. It was concluded that terpene
      hydroperoxides may occur in essential oils more frequently than anticipated, but
      are not recognized due to the principal blindness of capillary gas chromatography
      techniques and UV/vis LC-detectors.

PMID- 21941882
TI  - Antibacterial potential of citral derivatives.
AB  - Nine conjugated acid derivatives from monoterpene citral have been synthesized
      using ester, amide condensations, Wittig, Knoevenagel, Baylis-Hillman reactions
      and their antimicrobial activities were evaluated through disc diffusion and
      serial dilution methods. Several derivatives displayed interesting antimicrobial
      activity. Particularly, the Baylis-Hillman adducts 8-10 were found to have more
      potent antibacterial and antifungal activities than standard drugs namely
      chloramphenicol and nystatin respectively.

PMID- 21941883
TI  - A new bisabolene from Stevia tomentosa.
AB  - The new sesquiterpene (1R,2R,3R,6R,7S)-1-acetoxy-2,3-dihydroxy-2,3
      dihydrobisabolene (3) together with ten known terpenes and three known flavonoids
      were isolated from the aerial parts and from the roots of Stevia tomentosa. The
      structure of 3 follows from spectral studies, the relative chirality at C-3
      follows from 1H NMR coupling constants comparison with the corresponding
      calculated values obtained by applying a generalized Karplus-type relationship to
      the dihedral angles of model compounds, and the absolute configuration is assumed
      in analogy to known (2R,3R,6R,7S)-2,3-epoxy-2,3-dihydrobisabolen-1-one (2).

PMID- 21941884
TI  - Free radical scavenging activity-guided isolation of a diterpenoid from
      Plectranthus punuctatus.
AB  - Free radical scavenging activity-guided investigation of the acetone extract of
      Plectranthus punuctatus (L'Her) (Lamiaceae) resulted in the isolation of a novel
      diterpenoid 3,11,12,14,19-pentahydroxy-5,8,11,13-abietatraen-7-pyran[4,6]-16
      dione whose structure was elucidated based on spectral evidence. The isolated
      compound showed a significant antioxidant activity in the 1,1-diphenyl-2
      picrylhydrazyl (DPPH) and deoxyribose degradation assays with IC50 values of 9.65
      microg/mL and 5.25 microg/mL, respectively.

PMID- 21941885
TI  - Components from the steamed leaves of Acanthopanax koreanum and their effects on
      PPAR activity in HepG2 cells.
AB  - Three ent-kaurane diterpenes (1-3), four lupane-triterpene glycosides (4-7), and
      an oleanane-triterpene glycoside (8) were isolated from the ethyl acetate and
      water extracts of the steamed leaves of Acanthopanax koreanum using a combination
      of various column chromatographies. The structures of the isolates were
      determined by 1H-, 13C-NMR spectroscopy and mass spectrometry. To investigate the
      biological effects of the eight compounds (1-8) on peroxisome proliferator
      activated receptor gamma (PPARgamma), luciferase reporter assays were used. Among
      the tested compounds, ent-kaur-16-en-19-oic acid (1), 16alpha-hydroxy-ent-kauran
      19-oic acid (2), and 17-hydroxy-ent-kaur-15-en-19-oic acid (3) showed
      considerable effects on PPARgamma activity, compared with the positive control,
      troglitazone. To evaluate specificity and sensitivity of the active compounds (1
      3) in the regulation of transactivation of PPARs, Gal4-PPARs-LBD luciferase
      reporter assays were examined. In this study, the three ent-kaurane diterpenes (1
      3) were found to up-regulate PPARbeta/delta and PPARgamma activities, whereas
      they did not activate PPARalpha activity.

PMID- 21941886
TI  - Isolation and X-ray structure of deoxycholic acid from the sponge Ircinia sp.
AB  - Ethyl acetate extract of the sponge Ircinia sp., collected by SCUBA divers off
      the coast of southern India, contained a cholest-based sterol of insignificant
      antimicrobial activity, with one carboxylic acid side chain (3alpha, 7beta
      dihydroxy-5beta-cholan-24-oic acid, DCA). The structure of the compound was
      determined by spectroscopic data and single crystal X-ray diffraction studies.
      DCA crystallizes in the tetragonal space group P4(1)2(1)2, chirality documented
      by solution optical rotation [alpha]D = +67.4 degrees (c 0.16, CHCl3).

PMID- 21941887
TI  - Chemical constituents of the Gorgonian Dichotella fragilis (Ridleg) from the
      South China Sea.
AB  - Two new steroidal glycosides, fragilioside A (1) and fragilioside B (2), along
      with five known compounds (3-7) were isolated from the gorgonian Dichotella
      fragilis (Ridleg) collected from the South China Sea. The structures of the new
      compounds (1 and 2) were elucidated by comprehensive analysis of spectral data,
      especially 2D NMR. The brine shrimp lethality and antifouling activity of the
      isolated compounds were also evaluated.

PMID- 21941888
TI  - A new pyrrolidine derivative and steroids from an algicolous Gibberella zeae
      strain.
AB  - A new pyrrolidine derivative, 3-hydroxy-5-(hydroxymethyl)-4-(4'
      hydroxyphenoxy)pyrrolidin-2-one (1), and eight known steroids, (22E,24R)
      7beta,8beta-epoxy-3beta,5alpha,9alpha-trihydroxyergosta-22-en-6-one (2, a
      reassigned structure of (22E,24R)-5alpha,6alpha-epoxy-3beta,8beta,14alpha
      trihydroxyergosta-22-en-7-one), (22E,24R)-3beta,5alpha,9alpha-trihydroxyergosta
      7,22-dien-6-one (3), (22E,24R)-3beta,5alpha-dihydroxyergosta-7,22-dien-6-one (4),
      (22E,24R)-ergosta-7,22-dien-3beta/,5alpha,6beta-triol (5), (22E,24R)-ergosta-5,22
      dien-3beta-ol (6), (22E,24R)-5alpha,8alpha-epidioxyergosta-6,22-dien-3beta-ol
      (7), (22E,24R)-5alpha,8alpha-epidioxyergosta-6,9(11),22-trien-3beta-ol (8), and
      (22E,24R)-1(10 --> 6)-abeo-ergosta-5,7,9,22-tetraen-3alpha-ol (9), were isolated
      from the cultures of Gibberella zeae, an endophytic fungus isolated from the
      marine green alga Codium fragile. Their structures and relative stereochemistry
      were elucidated by 1D, 2D NMR and mass spectroscopic techniques. Compound 1
      showed cytotoxicity against A-549 and BEL-7402 cell lines.

PMID- 21941889
TI  - Szentiamide, an N-formylated cyclic depsipeptide from Xenorhabdus szentirmaii DSM
      16338T.
AB  - Szentiamide (1) a new cyclic hexadepsipeptide was isolated from the culture broth
      of the entomopathogenic bacterium Xenorhabdus szentirmaii DSM 16338T. The
      structure was elucidated by analysis of one- and two-dimensional NMR spectra and
      high resolution mass spectrometry. The amino acids were determined to be D
      leucine, L-threonine, D-phenylalanine, D-valine, L-tyrosine and L-tryptophane
      after hydrolysis and derivatization with D-FDVA [Nalpha-(2,4-dinitro-5
      fluorophenyl)-D-valinamide].

PMID- 21941890
TI  - Bioactive constituents from Michelia champaca.
AB  - (-)-Anonaine (1), (-)-asimilobine (2), (-)-nuciferine (3), (-)-anolobine (4), (-)
      romerine (5), (-)-N-acetylanonaine (6), liriodenine (7), (+)-syringaresinol (8),
      N-trans-feruloyltyramine (9), N-cis-feruloyltyramine (10), scopoletin (11), 4
      acetonyl-3,5-dimethoxy-p-quinol (12), vanillin (13), vanillic acid (14), syringic
      acid (15), beta-sitosterol (16) and stigmasterol (17) were isolated from branches
      of Michelia champaca L. In addition, a cell proliferation assay of five of the
      isolated compounds on human breast and lung cancer cells showed that liriodenine
      (7) was the strongest inhibitor.

PMID- 21941891
TI  - Inhibition of gastric H+, K(+)-ATPase activity by compounds from medicinal
      plants.
AB  - H+, K(+)-ATPase enzyme is a therapeutic target for the treatment of gastric
      disturbances. Several medicinal plants and isolated compounds inhibit the acid
      gastric secretion through interaction with the proton pump. In order to add new
      properties to some natural constituents, five compounds, a benzylated derivative
      of vincoside, a diterpene (abietic acid) and three alkaloids (cephaeline,
      vinblastine and vindoline), were tested for their activities on gastric H+, K(+)
      ATPase isolated from rabbit stomach. All the compounds inhibited H+, K(+)-ATPase
      activity with varied potency. The IC50 value for benzylvincoside was 121 (50-293)
      microM, and for abietic acid 177 (148-211) microM. The alkaloids cephaeline,
      vinblastine and vindoline inhibited the H+, K(+)-ATPase activity with IC50 values
      of 194, 761 and 846 microM, respectively. The results suggest that
      benzylvincoside, abietic acid and cephaeline can be important sources for the
      development of anti-secretor agents.

PMID- 21941892
TI  - GC/MS analysis of three Amaryllidaceae species and their cholinesterase activity.
AB  - Alzheimer's disease (AD), characterized by the death of nerve cells in the
      cerebral cortex, is the most common subtype of dementia. Despite the exponential
      growth in the number of AD patients, acetylcholinesterase (AChE) inhibitors are
      currently used to treat AD. Plants of the Amaryllidaceae family are known to
      synthesize a particular type of bioactive compounds, named Amaryllidaceae
      alkaloids, which have shown AChE inhibitory activity. Alkaloid extracts of three
      species of Amaryllidaceae were studied with respect to their acetylcholinesterase
      and butyrylcholinesterase inhibitory activity and alkaloid patterns. Eleven
      alkaloids were identified by GC/MS. Significant cholinesterase inhibitory
      activity was demonstrated by the alkaloid extract of N. undulata (IC50,(HuAChE) =
      14.3 +/- 1.2 microg/mL; IC50,(HuBuChE) = 33.9 +/- 1.9 microg/mL).

PMID- 21941893
TI  - Astrotricoumarin, an antiproliferative 4'-hydroxy-2',3'-dihydroprenylated
      methylcoumarin from an Astrotrichilia sp. from the Madagascar dry forest.
AB  - Bioassay guided fractionation of the ethanol extract of a new endemic species of
      the genus Astrotrichilia led to the isolation of the new antiproliferative 3-(4'
      hydroxy-2',3'-dihydroprenyl)-4,6-dimethoxy-5-methylcoumarin, named
      astrotricoumarin (8) with an IC50 value of 6.8 microM against the A2780 cell
      line. The structure of compound 8 was elucidated on the basis of its physical and
      spectroscopic data, including extensive 1D- and 2D-NMR analysis.

PMID- 21941894
TI  - A new chromene isolated from Ageratum conyzoides.
AB  - From the ethanol extract of the whole plant of Ageratum conyzoides L.
      (Compositae), one new chromene, 2,2-dimethylchromene 7-methoxy-6-O-beta-D
      glucopyranoside, was isolated, together with thirteen known compounds, seven of
      which were being reported for the first time. The compounds were all
      characterized by MS, IR, 1D- and 2D-NMR spectroscopy. 7,3',5'-Tri-O
      methyltricetin (7), precocene II (9), 3,5,7,4'-tetrahydroxyflavone (13) and
      5,6,7,3',4',5'-hexamethoxyflavone (14) exhibited inhibitory activity on the P-388
      cancer cell line with IC50 values of 12.8, 24.8, 3.5 and 7.8 microM respectively,
      while compound 9 exhibited inhibitory activity on the HT-29 cancer cell line with
      an IC50 value of 61 microM; the others showed no significant cytotoxic activity
      on the cell lines tested.

PMID- 21941895
TI  - Antifibrotic constituents from Garcinia mangostana.
AB  - From the CHCl3-soluble fraction of the fruits of Garcinia mangostana
      (Clusiaceae), six xanthone derivatives, alpha-mangostin (1), gamma-mangostin (2),
      gartanin (3), deoxygartanin (4), 1-isomangstanin (5) and garcinone E (6), were
      isolated. All these compounds significantly inhibited HSC-T6 viability as
      assessed by employing HSC-T6 hepatic stellate cells as an in vitro assay system.
      Among them, compounds 1 and 2, the most potent and major constituents of G.
      mangostana, inhibited HSC-T6 viability in dose- and time-dependent manners. In
      addition, compounds 1 and 2 significantly reduced collagen content, a
      pathological characteristic of liver fibrosis. Taken together, G. mangostana and
      its constituents might be beneficial for the treatment of liver fibrosis.

PMID- 21941896
TI  - Antioxidant and antimutagenic polyisoprenylated benzophenones and xanthones from
      Rheedia acuminata.
AB  - Dichloromethane extract of the stem bark of Rheedia acuminata yielded three
      benzophenones with antioxidant activity, the new one named acuminophenone A (1),
      guttiferone K (2) and isoxanthochymol (3), along with the known xanthones
      formoxanthone C (4) and macluraxanthone (5). The structures were established
      through interpretation of their spectroscopic data, the stereochemistry of
      compounds (1) and (2) were resolved by experimental and computational experiments
      and their antioxidant activities were measured using the DPPH, ABTS and TEAC
      assays. The antioxidant results showed that metabolites 1, 4 and 5 had a better
      antioxidant activity than the reference compound quercetin. In addition, we
      evaluate the mutagenicity and antimutagenicity of the CH2Cl2 extract as well as
      of the free radical scavenger compounds 1, 4 and 5 by the AMES
      Salmonella/microsomal test. No mutagenicity was found in the CH2Cl2 extract using
      Salmonella typhimurium strains TA98, TA100, TA102, TA1537 and TA1538, with or
      without S9 metabolic activation. The pure compounds neither showed mutagenicity
      in TA 102 strain and the most important result was the strong reduction of
      mutagenic effect induced by hydrogen peroxide in S. typhimurium TA102, with or
      without S9, showed by the compounds 1 (more than 93%) and 4 (more than 88%) at
      0.02 microg/plate.

PMID- 21941897
TI  - Anthraquinone profile, antioxidant and antimicrobial properties of bark extracts
      of Rhamnus catharticus and R. orbiculatus.
AB  - The anthraquinone profile, antioxidant and antimicrobial activities as well as
      the total phenol and total flavonoid contents were determined in methanol
      extracts of the barks of Rhamnus catharticus L. and R. orbiculatus Bornm. The
      most abundant anthraquinone derivatives in R. catharticus were physcion (67.8%)
      and emodin (26.2%), while R. orbiculatus contained mostly physcion (81.3%) and
      chrysophanol (14.6%). R. catharticus displayed better activity in the beta
      carotene-linoleic acid assay, as well as chelating activity, whereas its activity
      in the reducing power assay was significantly lower than that of R. orbiculatus.
      Both methanol extracts showed antimicrobial activity against all microbial
      species tested (Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli,
      Candida albicans, Aspergillus niger, Microsporum gypseum) with MIC values either
      equal to or lower than 2.50 mg/mL. R. catharticus and R. orbiculatus contained
      several anthranoid aglycones and their bark extracts demonstrated notable
      antioxidant and antimicrobial properties. The results obtained indicate the
      medicinal potential of these two species.

PMID- 21941898
TI  - Quantitative analysis of euglobals in Eucalyptus loxophleba leaves by qNMR.
AB  - A simple, rapid, accurate and selective 1H NMR spectroscopic method to detect and
      quantify euglobals in the leaves of Eucalyptus loxophleba ssp. lissophloia has
      been developed. The method allows for the estimation of total concentration of
      diformylphloroglucinol-monoterpene adducts, as well as the quantitation of
      sabinene- and alpha/beta-phellandrene-adducts, separately. The method was
      validated for accuracy, precision and linearity using as reference standards 2
      ethyl phenol and mixtures of jensenone, a monomeric formylated phloroglucinol,
      and 2-ethyl phenol.

PMID- 21941899
TI  - Evaluation of antioxidant activity of isoferulic acid in vitro.
AB  - Isoferulic acid (3-hydroxy-4-methoxycinnamic acid, IFA), the isomer of ferulic
      acid (4-hydroxy-3-methoxycinnamic acid), is a rare phenolic acid occurring in
      Rhizoma Cimicifugae. Unlike ferulic acid, which has been well investigated, the
      antioxidant activity of IFA has not been measured. In this study, IFA was
      systematically evaluated for its in vitro antioxidant activity for the first
      time. IC50 values were calculated of 7.30 +/- 0.57, 4.58 +/- 0.17, 1.08 +/- 0.01,
      8.84 +/- 0.43, 7.69 +/- 0.39, 1.57 +/- 0.2, 13.33 +/- 0.49 microg/mL,
      respectively, for lipid peroxidation, DPPH (1,1-diphenyl-2-picrylhydrazyl
      radical) and ABTS (3-ethylbenzthiazoline-6-sulfonic acid diammonium salt) radical
      scavenging, reducing power on Fe3+ and CU2+ ions, and hydroxyl and superoxide
      anion radical scavenging. Comparison with the IC50 values with those of the
      positive controls, Trolox and butylated hydroxyanisole (BHA), it can be concluded
      that isoferulic acid is an effective natural antioxidant in both lipid and
      aqueous media.

PMID- 21941900
TI  - Determination of caffeoyl quinic acids and flavonoids in Acanthopanax trifoliatus
      leaves by HPLC.
AB  - Extracts from the leaves of Acanthopanax trifoliatus, harvested at different
      seasons, were quantitatively analyzed for phenolic contents using high
      performance liquid chromatographic (HPLC) methods. Samples collected in winter
      contained high amounts of the major active components, mono and di-caffeoylquinic
      acid derivatives and flavonoid glycosides. It was found that January and November
      were the preferred periods for collecting plant material containing high amounts
      of caffeoyl quinic acid and flavonoid constituents.

PMID- 21941901
TI  - Amides and esters of phenylpropenoic acids from the aerial parts of Trifolium
      pallidum.
AB  - Two new derivatives of phenylpropenoic acids, N-trans-feruloyl-L-DOPA and O-trans
      caffeoyl-malic acid dimethyl ester, along with four known N-trans-caffeoyl-L-DOPA
      (clovamide), N-trans-caffeoyl-L-DOPA-methyl ester, O-trans-caffeoyl-malic acid, O
      trans-feruloyl-malic acid and quercetin 3-O-beta-D-glucopyranoside were isolated
      from the aerial parts of Trifolium pallidum. Their structures were elucidated by
      extensive spectroscopic methods including 1D- (1H, 13C) and 2D-NMR (DQF-COSY,
      HSQC, HMBC) experiments as well as mass spectrometry analysis.

PMID- 21941902
TI  - Amides from the stems of Cinnamomum burmannii.
AB  - A novel amide, cinnabutamine (1), along with five known amides, cinnaretamine
      (2), N-trans-caffeoyl-5-hydroxytyramine (3), N-trans-feruloyltyramine (4), N
      trans-feruloyl-5-methoxytyramine (5) and N-cis-feruloyl-5-methoxytyramine (6),
      were isolated from the stems of Cinnamomum burmannii (Lauraceae). Their
      structures were characterized and identified by spectral analysis.

PMID- 21941903
TI  - Phenolic composition, antioxidant capacity and antibacterial activity of selected
      Irish Brassica vegetables.
AB  - Vegetables belonging to the Brassicaceae family are rich in polyphenols,
      flavonoids and glucosinolates, and their hydrolysis products, which may have
      antibacterial, antioxidant and anticancer properties. In the present study,
      phenolic composition, antibacterial activity and antioxidant capacity of selected
      Brassica vegetables, including York cabbage, Brussels sprouts, broccoli and white
      cabbage were evaluated after extraction with aqueous methanol. Results obtained
      showed that York cabbage extract had the highest total phenolic content, which
      was 33.5, followed by 23.6, 20.4 and 18.4 mg GAE/g of dried weight (dw) of the
      extracts for broccoli, Brussels sprouts and white cabbage, respectively. All the
      vegetable extracts had high flavonoid contents in the order of 21.7, 17.5, 15.4
      and 8.75 mg QE/g of extract (dw) for York cabbage, broccoli, Brussels sprouts and
      white cabbage, respectively. HPLC-DAD analysis showed that different vegetables
      contain a mixture of distinct groups of phenolic compounds. All the extracts
      studied showed a rapid and concentration dependent antioxidant capacity in
      diverse antioxidant systems. The antibacterial activity was determined against
      Gram-positive and Gram-negative bacteria. York cabbage extract exhibited
      significantly higher antibacterial activity against Listeria monocytogenes (100%)
      and Salmonella abony (94.3%), being the most susceptible at a concentration of
      2.8%, whereas broccoli, Brussels sprouts and white cabbage had moderate to weak
      activity against all the test organisms. Good correlation (r2 0.97) was found
      between total phenolic content obtained by spectrophotometric analysis and the
      sum of the individual polyphenols monitored by HPLC-DAD.

PMID- 21941904
TI  - Dietary burden of phenolics per serving of "Mountain tea" (Sideritis) from
      Macedonia and correlation to antioxidant activity.
AB  - This work was afforded from 2 points of view, phytochemical evaluation and
      relation to antioxidant activity and dietary burden of phenolics of a cup of
      "Mountain tea", a drink obtained by domestic infusion of Sideritis.
      Phytochemically, two extraction protocols using water and methanol as solvent
      were used for comparison. Methanol and boiling water extracts (by domestic
      infusion procedure) showed that extracts were rich in bound forms of phenolics
      such as hydroxycinnamic acids, phenylethanoid glycosides and flavonoid
      glycosides. The total phenolic content for Sideritis species ranged around 190 mg
      per serving (2 g infusion bag) for methanol extracts and around 72 mg per serving
      in water extracts. Among the two different Macedonian Sideritis species,
      Sideritis raeseri (wild growing) showed the highest phenolics content in both
      extracts (212 mg and 89 mg per serving, respectively). Concerning the phenolic
      content in the different aerial parts, leaf was the richest plant organ in
      phenolics followed by flower and stem with the lowest amount. The methanol
      extract from Sideritis raeseri (wild growing) showed the highest antioxidant
      capacity as shown by DPPH, ABTS and FRAP assays. The antioxidant capacity was
      linearly correlated with phenolic content. Nutritionally, the dietary burden of
      phenolics of a "Mountain tea" bag for domestic infusion (serving size) was
      established at 89 mg for an homogeneous and equal distribution of the different
      aerial parts (leaf, flower and stem). However, and according to our results a
      rate of 60% leaf and 40% flower would increase the content of bioavailable
      phenolics and also the total phenolics content of a serving bag of "Mountain
      tea".

PMID- 21941905
TI  - Aqueous extract from Vitis vinifera tendrils is able to enrich keratinocyte
      antioxidant defences.
AB  - An aqueous extract of V. vinifera L. tendrils was evaluated for its ability to
      enrich the antioxidant capacity of cultured cells. The long-time antioxidant
      capability of the extract was measured by in vitro chemical methods, and its
      influence on reduced glutathione levels and plasma membrane oxido reductase
      activity was determined in cultured human keratinocytes (NCTC 2544).
      Keratinocytes are cells normally exposed to oxidative stress, and for this reason
      adequately equipped with antioxidant defences. However, it has long been
      suggested that exogenous antioxidants may play an important role in minimizing
      the adverse effects of oxidative stress on skin.We demonstrated that V. vinifera
      tendril aqueous extract was able to increase, in a time- and dose-dependent
      manner, the reduced glutathione concentration and activity of trans plasma
      membrane oxido reductase as an indirect evaluation of the intracellular redox
      status of the cells demonstrating a relevant antioxidant activity of this
      phytocomplex.

PMID- 21941906
TI  - A new acylated neohesperidoside from Geranium purpureum.
AB  - A new acylated neohesperoside derivative, 1-octyl-4'-isovaleroyl-neohesperoside
      (1), was isolated from Geranium purpureum Vill. (Geraniaceae) together with the
      known compounds quercetin-3-rutinoside and gallic acid. The identification of the
      isolated compounds was carried out by spectroscopic analysis including 1D- and 2D
      NMR (1H, 13C, COSY, HSQC and HMBC) spectroscopy and ESI-TOF-MS.

PMID- 21941907
TI  - Synthesis and field test of three candidates for soybean pod borer's sex
      pheromone.
AB  - Three candidates for the soybean pod borer's sex pheromone, dodec-10-en-1-yl
      acetate (E:Z = 95:5) (9a), (E, E)-dodeca-8, 10-dien-1-yl acetate (9b) and (E)
      dodec-8-en-1-yl acetate (9c), were synthesized through the coupling reaction
      between Grignard reagents and acetates catalyzed by Li2CuCl4. Furthermore, the
      compounds 9a, 9b, and 9c, when tested in the field, showed that dodec-10-en-1-yl
      acetate (E:Z = 95:5) (9a) has promise as a lure for male soybean pod borer.

PMID- 21941908
TI  - Chemical investigation of carrageenan from the red alga Sarconema filiforme
      (Gigartinales, Rhodophyta) of Indian waters.
AB  - Sulphated galactan (SF(A)) containing alpha (alpha), iota (i) and pyruvated alpha
      carrageenans (17.6:18.8:25.3 mol %) was extracted and characterized from
      Sarconema filiforme of Indian waters. The SF(A) and its alkali modified
      derivative (SF(AM)) were composed of D-galactose, 3, 6-anhydro-D-galactose, 6-O
      methylated-D-galactose (64.5:23.0:9.8 and 59.6:29.8:7.6 mol %) respectively. The
      linkage analysis, physicochemical analysis, infra red and 13C nuclear magnetic
      resonance spectra of SFA along with linkage analysis of the desulphated
      derivative (SF(D)) of SFA, reveals that it was a hybrid/combination of alpha/iota
      carrageenan as well as 3-linked 4',6'-O-(1-carboxyethylidene)-galactose
      (pyruvated alpha carrageenan) and 6-O-methylated alpha-carrageenan. The flow
      behavior of SF(A) obtained from rheological measurements suggested strong network
      formation in presence of 1% aqueous KCl and CaCl2 solutions.

PMID- 21941909
TI  - Monitoring the emission of volatile organic compounds from flowers of Jasminum
      sambac using solid-phase micro-extraction fibers and gas chromatography with mass
      spectrometry detection.
AB  - Solid-phase micro-extraction (SPME) was studied as a solvent free alternative
      method for the extraction and characterization of volatile compounds in intact
      and plucked flowers of Jasminum sambac at different day time intervals using gas
      chromatography (GC-FID) and gas chromatography-quadrupole mass spectrometry. The
      analytes identified included alcohols, esters, phenolic compounds, and
      terpenoids. The main constituents identified in the flower aroma using different
      fibers were cis-3-hexenyl acetate, (E)-beta-ocimene, linalool, benzyl acetate,
      and (E,E)-alpha-farnesene. The benzyl acetate proportion decreased from morning
      to afternoon and then increased in evening collections. PDMS fiber showed a high
      proportion of (E,E)-alpha-farnesene in jasmine floral aroma. Among other
      constituents identified, cis-3-hexenyl acetate, linalool, and benzyl acetate were
      major aroma contributors in plucked and living flowers extracts using PDMS/DVB,
      Carboxen/PDMS, and DVB/Carboxen/PDMS fibers. PDMS/DVB recorded the highest
      emission for benzyl acetate while the (E)-beta-ocimene proportion was highest in
      DVB/Carboxen/PDMS when compared with the rest. The highest linalool content, with
      increasing proportion from morning to noon, was found using mixed coating fibers.
      Almost negligible volatile adsorption was recorded for the polyacrylate fiber for
      intact flower aroma, whereas it was most effective for benzyl acetate, followed
      by indole under plucked conditions. Moreover, the highest amounts extracted,
      evaluated from the sum of peak areas, were achieved using Carboxen/PDMS, and
      DVB/Carboxen/PDMS. Introduction of a rapid, and solvent free SPME method for the
      analysis of multicomponent volatiles can be successfully employed to monitor the
      extraction and characterization of flower aroma constituents.

PMID- 21941910
TI  - Volatile components from aerial parts of Centaurea gracilenta and C. ovina ssp.
      besserana growing wild in Bulgaria.
AB  - The essential oils of Centaurea gracilenta Velen. (CG) and C. ovina Pall. ex
      Willd. ssp. besserana (DC.) Dostal (COB) growing wild in Bulgaria, were studied
      by GC and GC-MS. Forty-five compounds for CG, representing the 90.1% of the oil,
      and 68 compounds for COB, representing the 91.9% of the oil, were identified. The
      oils were rich in sesquiterpenoids (33.4% for CG and 27.3% for COB), hydrocarbons
      (28.3% for CG and 10.7% for COB) and carbonylic compounds (12.7% for CG and 13.1%
      for COB). Fatty acids were abundant only for COB (31.3%). beta-Eudesmol (12.8%),
      nonacosane (11.8%) and p-vinyl guiacol (7.5%) were recognized as the main
      constituents for CG, while hexadecanoic acid (21.4%), spathulenol (7.9%), beta
      eudesmol (5.8%) and caryophyllene oxide (5.7%) were the main compounds for COB.

PMID- 21941911
TI  - Variability of essential oils of Betonica officinalis (Lamiaceae) from different
      wild populations in Kosovo.
AB  - The aerial parts and roots of Betonica officinalis were collected from three
      localities characterized by different ecological conditions to study the natural
      variability of the chemical composition of the essential oils in this plant. The
      leaves and inflorescences were collected during the flowering time, whereas the
      roots were collected at the end of the vegetative period. The plant material was
      dried at room temperature. The essential oils were obtained by micro-steam
      hydrodistillation and analyzed using gas chromatography (GC) and gas
      chromatography-mass spectrometry (GC-MS). Overall, 69 constituents were
      identified in all localities and plant parts. The main compositions of the leaves
      in all localities were alpha-pinene, 1-octen-3-ol, beta-bourbonene, (E)
      caryophyllene and germacrene D. The essential oil of the inflorescences was
      characterized by these main constituents: alpha-pinene, (E)-caryophyllene and
      trans-beta-farnesene. In all localities, the percentages of alpha-pinene and (E)
      caryophyllene were higher in the inflorescences than in the leaves, whereas
      nonane was the main constituent in the roots.

PMID- 21941912
TI  - Analysis of essential oils from Scutellaria orientalis ssp. alpina and S.
      utriculata by GC and GC-MS.
AB  - The chemical composition of the essential oils obtained from aerial parts of
      Scutellaria orientalis L. ssp. alpina (Boiss.) O. Schwarz and S. utriculata
      Labill. growing wild in Lebanon, were analyzed by GC and GC-MS. In S. orientalis
      ssp. alpina, strongly characterized by sesquiterpenes (41.2%) and particularly
      sesquiterpene hydrocarbons (31.7%), hexahydrofarnesylacetone (11.7%) was
      recognized as the main constituent, together with hexadecanoic acid (7.6%),
      caryophyllene (7.4%), caryophyllene oxide (6.8%), 4-vinylguaiacol (5.4%) and
      germacrene D (5.4%). S. utriculata oil was instead constituted above all by
      monoterpenes (42.2%), particularly oxygen containing monoterpenes (39.9%), and in
      this oil the main compounds were linalool (20.1%), 4-vinyl guaiacol (15.5%),
      alpha-terpineol (8.9%), (E)-nerolidol (8.9%) and geraniol (8.2%).

PMID- 21941913
TI  - Antibacterial activity and GC/MS analysis of the essential oils from flower, leaf
      and stem of Origanum vulgare ssp. viride growing wild in north-west Iran.
AB  - Essential oils obtained from flowers, leaves and stems of Origanum vulgare L.
      ssp. viride (Boiss.) Hayek., growing wild in Ardabil Province (north-west Iran),
      were analyzed by GC and GC/MS. beta-Caryophyllene was the major constituent in
      all three oils (48.1%, 50.1% and 60.2%, respectively). Of the 19 components
      detected in the flower oil, comprising 96.3% of the total, the major components
      were 1,8-cineole (11.6%), alpha-pinene (6.9%), and gamma-cadinene (4.8%). 1-Octen
      3-ol (23.8%), and 1,8-cineole (8.5%) predominated in the leafoil. In the stem
      oil, other main constituents were bicyclogermacrene (9.8%), 1,8-cineole (6.4%),
      borneol (5.1%), and pinocarvone (4.4%). The essential oils were evaluated for
      their antibacterial activity against 10 selected microorganisms. The data
      obtained contribute to the future use of certain essential oils as natural
      preservatives for food products, due to their safety and positive effect on shelf
      life.

PMID- 21941914
TI  - Composition of Satureja kitaibelii essential oil and its antimicrobial activity.
AB  - The composition of the essential oil obtained by hydrodistillation from the
      aerial parts of Satureja kitaibelii from Rtanj mountain (Serbia), collected
      during three years, was studied. Thirty-nine components were identified in each
      sample of S. kitaibelii essential oil, representing about 87% of the oils. p
      Cymene was the most dominant compound in all three oils (27.9%, 14.7% and 24.4%,
      respectively). The simple formulation of a lozenge with 0.2% of S. kitaibelii
      essential oil was prepared and the antimicrobial activity of the essential oil
      and the lozenge with essential oil was tested using a broth microdilution assay.
      Both essential oil and lozenge possessed strong antimicrobial activity with MIC
      values of 0.10-25 microg/mL, and 0.97-15.6 mg/mL, respectively.

PMID- 21941915
TI  - Composition and antifungal activities of the leaf essential oil of Neolitsea
      parvigemma from Taiwan.
AB  - The hydrodistillated leaf essential oil of Neolitsea parvigemma was analyzed to
      determine its composition and yield. Sixty-two compounds were identified, the
      main components being beta-caryophyllene (14.2%), beta-eudesmol (12.9%), alpha
      cadinol (10.2%) and tau-cadinol (8.8%). Oxygenated sesquiterpenes (48.9%) and
      sesquiterpene hydrocarbons (48.8%) were the predominant groups of compounds. The
      antifungal indexes of the leaf oil against the 7 fungi, Aspergillus clavatus, A.
      niger, Chaetomium globosum, Cladosporium cladosporioides, Myrothecium verrucaria,
      Penicillium citrinum and Trichoderma viride, were 100.0, 72.3, 100.0, 100.0,
      100.0, 75.8 and 88.6% at a 1 mg/mL concentration, respectively. The oil also
      exhibited anti-wood-decay-fungi activity against Trametes versicolor,
      Phaneochaete chrysosporium, Phaeolus schweintizii, and Lenzites sulphureu with
      MIC values of 50, 50, 25 and 25 microg/mL, respectively. For the antifungal and
      anti-wood-decay fungal activities of the oil, the active source compounds were
      determined to be alpha-cadinol, beta-eudesmol and tau-cadinol.

PMID- 21941916
TI  - Antioxidant capacity and larvicidal and antifungal activities of essential oils
      and extracts from Piper krukoffii.
AB  - The leaves and twigs of Piper krukoffii, collected in the Carajas National
      Forest, north Brazil, yielded essential oils (2.0% and 0.8%), the main
      constituents of which were myristicin (40.3% and 26.7%), apiole (25.4% and 34.1%)
      and elemicin (2.8% and 3.0%). The antioxidant activities of the oils, methanol
      extract and its sub-fractions were evaluated. The DPPH EC50 values varied from
      the ethyl acetate sub-fraction (73.4 +/- 3.7 microg/mL) to the methanol extract
      (24.9 +/- 0.8 microg/mL), and the ABTS TEAC values ranged in the same order from
      265.7 to 349.2 microMol TE/g. These results indicated a significant antioxidant
      activity for the plant. The lignans (-)-kusunokin, yatein, (-)-hinokin and
      cubebin were identified in the methanol extract. The hydro-methanolic sub
      fraction showed a high value for total phenol content (106.5 +/- 0.7 mg GAE/g),
      as well as 1H NMR signals for sugar moieties. Crude extracts and sub-fractions
      were also able to inhibit beta-carotene bleaching, varying from 22.4 to 47.1%.
      The oils from the leaves and twigs showed strong larvicidal (21.4 and 3.6
      microg/mL) and fungicide (0.5 and 0.1 microg/mL) activities.

PMID- 21941917
TI  - Evaluation of Clausena anisata essential oil from Cameroon for controlling food
      spoilage fungi and its potential use as an antiradical agent.
AB  - Investigations were conducted to determine the chemical composition, antifungal
      and antiradical activities of the essential oil extracted from the fresh leaves
      of Clausena anisata (Willd.) Hook. F. ex Benth (from Cameroon) against
      Aspergillus flavus, A. niger, A. parasiticus and Fusarium moniliforme. The
      essential oil obtained by hydrodistillation was analysed by GC and GC/MS. The
      disc diffusion method was used to evaluate the fungal growth inhibition at
      various concentrations of the oil while the antiradical activity of the essential
      oil was studied by the DPPH (diphenyl picryl hydrazyl) method. The main
      components obtained were E-ocimenone (15.1%), Z-ocimenone (11.5%), gamma
      terpinene (11.4%) and germacrene D (10.9%). After 10 days of incubation on
      essential oil supplemented medium, the growth of A. flavus, A. niger, A.
      parasiticus and F. moniliforme were totally inhibited by 4, 5, 5 and 5 mg/mL of
      C. anisata essential oil, respectively. The antiradical activity of C. anisata
      essential oil (SC50 = 5.1 g/L) was less than that of butylated hydroxyl toluene
      (BHT), which was used as the reference compound (SC50 = 0.007 g/L). Results
      obtained in the present study indicate the possibility of exploiting C. anisata
      essential oil to fight strains of A. flavus, A. niger, A. parasiticus and F.
      moniliforme responsible for biodeterioration of stored food products.

PMID- 21941918
TI  - Chemical diversity in Mentha spicata: antioxidant and potato sprout inhibition
      activity of its essential oils.
AB  - The essential oils from fresh aerial parts of Mentha spicata L. collected from
      ten different natural habitats of Uttarakhand, India were analyzed by a
      combination of GC, GC/MS and NMR spectroscopy. The analysis revealed that
      monoterpenoids (46.1%-91.6%), mainly carvone (15.3%-68.5%), piperetenone oxide
      (24.0%-79.2%) and alpha-humulene (0.1%-29.9%), were the major constituents of the
      essential oils, but with significant qualitative and quantitative differences
      among the other constituents. Cluster analysis of the oil composition was carried
      out in order to discern the differences and similarities within different
      accessions collected from different natural habitats. The essential oils were
      also screened for their antioxidant activities by chelating properties of Fe2+,
      DPPH radical-scavenging activity, and their reducing power. The essential oils of
      two chemo variants (viz. carvone and piperetenone oxide types) were also tested
      for potato (Solanum tuberosum L.) sprout suppressant activity. The results showed
      that these oils exhibit good sprout inhibition activity in comparison to CIPC and
      iodine, the standard sprout suppressant.

PMID- 21941919
TI  - Role of direct bioautographic method for detection of antistaphylococcal activity
      of essential oils.
AB  - The aim of the present study was the chemical characterization of some
      traditionally used and therapeutically relevant essential oils (thyme,
      eucalyptus, cinnamon bark, clove, and tea tree) and the optimized microbiological
      investigation of the effect of these oils on clinical isolates of methicillin
      resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus
      (MSSA). The chemical composition of the oils was analyzed by TLC, and controlled
      by gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS). The
      antibacterial effect was investigated using a TLC-bioautographic method.
      Antibacterial activity of thyme, clove and cinnamon oils, as well as their main
      components (thymol, carvacrol, eugenol, and cinnamic aldehyde) was observed
      against all the bacterial strains used in this study. The essential oils of
      eucalyptus and tea tree showed weak activity in the bioautographic system. On the
      whole, the antibacterial activity of the essential oils could be related to their
      most abundant components, but the effect of the minor components should also be
      taken into consideration. Direct bioautography is more cost-effective and better
      in comparison with traditional microbiological laboratory methods (e.g. disc
      diffusion, agar-plate technique).

PMID- 21941920
TI  - Antiphytoviral activity of essential oil from endemic species Teucrium arduini.
AB  - The essential oil of Teucrium arduini L. was characterized by a high
      concentration of sesquiterpene hydrocarbons (43.8%) of which beta-caryophyllene
      (19.9%) being the major compound, followed by oxygenated sesquiterpenes (19.6%)
      of which caryophyllene-oxide (14.6%) was dominant. When applied to plants of
      Chenopodium amaranticolor and Ch. quinoa for two successive days prior
      inoculation, the oil was effective in reducing lesion numbers on plants infected
      with Tobacco mosaic virus (25.7%) and Cucumber mosaic virus (21.9%). The main
      components of oil, beta-caryophyllene and caryophyllene oxide showed potent
      antiviral activity against CMV, but weak activity against TMV infection.

PMID- 21941921
TI  - Toxic effects of Citrus aurantium and C. limon essential oils on Spodoptera
      frugiperda (Lepidoptera: Noctuidae).
AB  - Citrus aurantium and C. limon were selected in the search for natural plant
      insecticides. The essential oils of C. aurantium and C. limon and ethanol
      extracts of the seeds, pulp, albedo, and peel of C. aurantium were incorporated
      into the larval diet of the lepidopteran pest Spodoptera frugiperda. Larval and
      pupal mortality were quantified and adult malformation was observed. C aurantium
      essential oil had antifeedant action and the mixture of albedo ethanol extract
      and C aurantium essential oil had toxic effects on S. frugiperda larvae at early
      stages, when they had not yet produced major damage to the crop. Our results
      indicated that a mixture of ethanol extract of albedo and C. aurantium essential
      oil (250 microg of extract mix per g of diet) deterred feeding by 46% and had the
      highest larval mortality (100%) of the materials tested. The peel extract (250
      microg per g of diet) produced an increment in growth rate and diet consumption.
      However, 40% of the larval and 45% of the pupal populations died after 96 h of
      treatment. The blend of essential oil and C. aurantium albedo ethanol extract
      showed the lowest consumption and a poor nutrient conversion into biomass.
      Finally, the presence of D-limonene and nootkatone in the peel ethanol extract,
      and C. limon and C. aurantium essential oils, may be the cause of the response in
      the feeding behavior and toxic effects found on S. frugiperda.

PMID- 21941922
TI  - Neutralizing effects of Nectandra angustifolia extracts against Bothrops neuwiedi
      snake venom.
AB  - Leaves extracts and essential oil of Nectandra angustifolia were explored for the
      first time for neutralization of Bothrops neuwiedi diporus snake venom. The
      ethanol extract was the most active and inhibited both venom activities
      (hemolytic and coagulant), while the oil was only active on the coagulant
      activity. These observations confirmed that certain medicinal plants from
      Corrientes and Chaco Provinces possess significant snake venom neutralizing
      capacity and need further examination for their active constituents. Analysis by
      GC and GC-MS of the essential oil and the enantiomeric excess found for alpha
      pinene, beta-pinene and limonene allowed a better characterization of this
      species.

PMID- 21941923
TI  - Artocarpus plants as a potential source of skin whitening agents.
AB  - Artocarpus plants have been a focus of constant attention due to the potential
      for skin whitening agents. In the in vitro experiment, compounds from the
      Artocarpus plants, such as artocarpanone, norartocarpetin, artocarpesin,
      artogomezianol, andalasin, artocarbene, and chlorophorin showed tyrosinase
      inhibitory activity. Structure-activity investigations revealed that the 4
      substituted resorcinol moiety in these compounds was responsible for their potent
      inhibitory activities on tyrosinase. In the in vitro assay, using B16 melanoma
      cells, the prenylated polyphenols isolated from Artocarpus plants, such as
      artocarpin, cudraflavone C, 6-prenylapigenin, kuwanon C, norartocarpin, albanin
      A, cudraflavone B, and brosimone I showed potent inhibitory activity on melanin
      formation. Structure-activity investigations revealed that the introduction of an
      isoprenoid moiety to a non-isoprenoid-substituted polyphenol enhanced the
      inhibitory activity of melanin production in B16 melanoma cells. In the in vivo
      investigation, the extract of the wood of Artocarpus incisus and a representative
      isolated compound from it, artocarpin had a lightening effect on the skin of
      guinea pigs' backs. Other in vivo experiments using human volunteers have shown
      that water extract of Artocarpus lakoocha reduced the melanin formation in the
      skin of volunteers. These results indicate that the extracts of Artocarpus plants
      are potential sources for skin whitening agents.

PMID- 21941925
TI  - Nursing is key to success of ACOs.

PMID- 21941924
TI  - Mining invertebrate natural products for future therapeutic treasure.
AB  - This review focuses on biologically active entities from invertebrate sources,
      especially snails. The reader will encounter several categories of compounds from
      snails including glycosaminoglycans, peptides, proteins (glycoproteins), and
      enzymes which possess diverse biological activities. Among glycosaminoglycans,
      acharan sulfate which was isolated from a giant African snail Acahtina fulica is
      reviewed extensively. Conotoxins which are also called conopeptides are unique
      peptide mixtures from marine cone snail. Conotoxins are secreted to capture its
      prey, and currently have the potential to be highly effective drug candidates.
      One of the conotoxins is now in the market as a pain killer. Proteins as well as
      glycoproteins in the snail are known to be involved in the host defense process
      from an attack of diverse pathogens. Carbohydrate-degrading enzymes characterized
      and purified in snails are introduced to give an insight into the applicability
      in glycobiology research such as synthesis and structure characterization of
      glycoconjugates. It seems that simple snails produce very complicated biological
      compounds which could be an invaluable source in future therapeutics as well as
      research areas in natural medicine.

PMID- 21941926
TI  - What about ethics?

PMID- 21941927
TI  - After an attempt: caring for the suicidal patient on the medical-surgical unit.
AB  - Suicide risk for a patient is highest immediately after an attempt. A patient may
      be treated and stabilized on a medical-surgical unit, where staff may not have
      the necessary resources and training to maintain patient safety. Care concerns
      for the suicidal patient are addressed, and recommendations regarding staff
      training and patient safety are offered.

PMID- 21941928
TI  - Nurse practitioner students' perceptions of fibromyalgia pain and quality of
      life.
AB  - Perceptions of NP students were explored regarding fibromyalgia syndrome (FMS)
      pain and quality of life (QOL), and their preparedness in treating these issues.
      Participants acknowledged the importance of FMS pain control and QOL issues.
      However, they lacked confidence in treating FMS pain.confidence in treating MS
      pain.

PMID- 21941929
TI  - Pulling the plug on brain-drain: understanding international migration of nurses.
AB  - The reliance on foreign nurses is symptomatic of ineffective staffing practices
      affecting health care professionals, particularly nurses, in the United States
      and other industrialized nations. This demonstrates a failure to alleviate the
      nursing shortage. The influx of foreign nurses (brain-drain) has serious
      ramifications that should be explored fully.

PMID- 21941930
TI  - The effects of correction insulin and basal insulin on inpatient glycemic
      control.
AB  - Hospitalized patients with type 2 diabetes may benefit from tighter glycemic
      control to prevent hyperglycemia and its complications. The glycemic control of
      two groups of inpatients with diabetes receiving subcutaneous insulin via a basal
      bolus approach or sliding scale was compared.

PMID- 21941931
TI  - Nurse-physician rounds: a collaborative approach to improving communication,
      efficiencies, and perception of care.

PMID- 21941932
TI  - Nurse's role in increasing patient access to hospice care.

PMID- 21941934
TI  - In this together.

PMID- 21941933
TI  - Comprehensive case study--acute stroke.

PMID- 21941935
TI  - LVAD deactivation.

PMID- 21941936
TI  - Cloning, protein expression and display of synthetic multi-epitope mycobacterial
      antigens on Salmonella typhi Ty21a cell surface.
AB  - Expressing proteins of interest as fusion to proteins of bacterial envelope is a
      powerful technique for biotechnological and medical applications. The synthetic
      gene (VacII) encoding for T-cell epitopes of selected genes of Mycobacterium
      tuberculosis namely, ESAT6, MTP40, 38 kDa, and MPT64 was fused with N- terminus
      of Pseudomonas syringae ice nucleation protein (INP) outer membrane protein. The
      fused genes were cloned into a bacterial expression vector pKK223-3. The
      recombinant protein was purified by Ni-NAT column. VacII gene was displayed on
      the cell surface of Salmonella typhi Ty21a using N-terminal region of ice
      nucleation proteins (INP) as an anchoring motif. Glycine method confirmed that
      VacII was anchored on the cell surface. Western blot analysis further identified
      the synthesis of INP derivatives containing the N-terminal domain INP- VacII
      fusion protein of the expected size (52 kDa).

PMID- 21941937
TI  - Characterization and in vitro expression of non-structural 1 protein of canine
      parvovirus (CPV-2) in mammalian cell line.
AB  - Parvoviruses are small, 260-A-diameter, icosahedral, non-enveloped, single
      stranded DNA viruses with a genome of approximately 5 kb. Non structural protein,
      (NS-1) is especially relevant, being both essential for virus replication and the
      main factor responsible for virus pathogenicity and cytotoxicity. This protein
      has also been reported to possess the property of killing of transformed cells.
      The present study was carried out to clone, characterize and express the NS-1
      gene of canine parvovirus. NS-1 complete CDS 2020bp was amplified, cloned into
      eukaryotic expression vector pcDNA 3.1(+), sequenced and characterized by in
      vitro expression analysis. Functional activity of recombinant construct,
      pcDNA.cpv.NS-1, was evaluated by RT-PCR and flow cytometry for the expression of
      NS-1 specific mRNA and NS-1 protein, respectively, in transfected HeLa cells.
      This recombinant plasmid may serve as an important tool to evaluate the apoptotic
      potential of NS-1 protein of canine parvovirus in cultured HeLa cells.

PMID- 21941938
TI  - Involvement of AMPA receptors for Mesobuthus tamulus Pocock venom-induced
      depression of monosynaptic reflex in neonatal rat spinal cord in vitro.
AB  - Glutamate is a putative neurotransmitter at Ia-alpha motoneuron synapse in the
      spinal cord and mediate the action via N-methyl-D-aspartate (NMDA) and a-amino-3
      hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors. Since NMDA receptors
      are not involved in M. tamulus Pocock (MBT) venom-induced depression of spinal
      monosynaptic reflex (MSR), the present study was undertaken to evaluate the role
      of AMPA receptors in mediating the depression of MSR by MBT venom. The
      experiments were performed on isolated hemisected spinal cord from 4-6 day old
      rats. Stimulation of a dorsal root with supramaximal voltage evoked MSR and
      polysynaptic reflex (PSR) potentials in the corresponding segmental ventral root.
      Superfusion of MBT venom (0.3 microg/ml) depressed the spinal reflexes in a time
      dependent manner. The maximum depression of MSR(approximately 66%) was seen at 10
      min and it was 25 min for PSR (approximately 75%). The time to produce 50%
      depression of MSR and PSR was 6.7+/- 1.5 and 10.8 +/- 2.6 min, respectively.
      Pretreatment of the cords with 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX, 0.1
      microM), an AMPA receptor antagonist, blocked the venom-induced depression of MSR
      but not PSR. The results indicate that venom-induced depression of MSR is
      mediated via AMPA receptors.

PMID- 21941939
TI  - Effect of nitric oxide in protective effect of melatonin against chronic
      constriction sciatic nerve injury induced neuropathic pain in rats.
AB  - Developing a successful treatment strategy for neuropathic pain has remained a
      challenge among researcher and clinicians. Various animal models have been
      employed to understand the pathogenic mechanism of neuropathic pain in
      experimental animals. The present study was designed to explore the possible
      nitric oxide mechanism in the protective effect of melatonin against chronic
      constriction injury (CCI) of sciatic nerve in rats. Following chronic
      constriction injury, various behavioral tests (thermal hyperalgesia, cold
      allodynia) and biochemical parameters (lipid peroxidation, reduced glutathione,
      catalase, and nitrite) were assessed in sciatic nerves. Drugs were administered
      for 21 consecutive days from the day of surgery. CCI significantly caused thermal
      hyperalgesia, cold allodynia and oxidative damage. Chronic administration of
      melatonin (2.5 or 5 mg/kg, ip) significantly attenuated hyperalgesia, cold
      allodynia and oxidative damage in sciatic nerves as compared to CCI group.
      Further, L-NAME (5 mg/kg) pretreatment with sub-effective dose of melatonin (2.5
      mg/kg, ip) significantly potentiated melatonin's protective effect which was
      significant as compared to their individual effect per se. However, L-arginine
      (100 mg/kg) pretreatment with melatonin (2.5 mg/kg, ip) significantly reversed
      its protective effects. Results of the present study suggest the involvement of
      nitric oxide pathway in the protective effect of melatonin against CCI-induced
      behavioral and biochemical alterations in rats.

PMID- 21941940
TI  - Effect of combination of thalidomide and sulfasalazine in experimentally induced
      inflammatory bowel disease in rats.
AB  - Thalidomide provided significant protection against tri nitro benzene sulfonic
      acid induced colitis. Combination therapy also reduced colonic inflammation and
      all the biochemical parameters (myeloperoxidase assay, malondialdehyde assay and
      tumor necrosis factor-alpha, estimation) were significant as compared to control
      as well as thalidomide alone treated group. Combination therapy showed additive
      effect of thalidomide which restored lipid peroxidation as well as reduced
      myeloperoxidase and TNF-a towards the normal levels. Morphological and
      histological scores were significantly reduced in combination groups. In
      experimental model of colitis, oral administration of thalidomide (150 mg/kg)
      alone as well as its combination with sulfasalazine (360 mg/kg) significantly
      reduced the colonic inflammation. The results indicate the additive effect of
      thalidomide with sulfasalazine in rat colitis model which requires further
      confirmation in human studies.

PMID- 21941941
TI  - Effect of Zataria multiflora Bois L. on histamine (H1) receptor of guinea pig
      tracheal chains.
AB  - The effects of three concentrations (2.5, 5 and 10 microg/ml) of aqueous
      ethanolic extract of Z. multiflora bois, 10 nM chlorpheniramine, and saline on
      histamine (H1) receptors were tested on two groups of guinea pig tracheal chains
      [trachea incubated with indomethacin (Gr. 1), and indomethacin and propranolol
      (Gr. 2)]. The effective concentration of histamine causing 50% of maximum
      response (EC50) obtained in presence of chlorpheniramine in both groups, all
      concentrations of the extract in group 1 and its two higher concentrations in
      group 2 were significantly greater than those of saline. The values of
      concentration ratio minus one (CR-1) obtained in presence of all the three
      concentrations of the extract in group 1 and 10 microg/ml concentration in group
      2 were significantly greater than those of chlorpheniramine. The values of EC50
      obtained in presence of all the three concentrations of extract and CR-1 obtained
      in the presence of 2.5 and 5 microg/ml concentrations in group 2 were lower than
      group 1. There was not significant difference in maximum response obtained in
      presence of different concentrations of extract between two groups. There were
      parallel right ward shift in concentration response curves obtained in presence
      of all concentrations of the extract in both the groups. These results indicated
      an inhibitory effect of Z. multiflora at histamine H1 receptors.

PMID- 21941942
TI  - Effect of oleic, lauric and myristic acids on phenylephrine-induced contractions
      of isolated rat vas deferens.
AB  - D-004, a lipid extract of Roystonea regia fruits that contains oleic, lauric and
      myristic acids as major components inhibits alpha1-adrenoreceptors-mediated
      contractile responses in isolated rat vas deferens and prostate trips; no study
      has demonstrated a similar effect for oleic, lauric or myristic acids
      individually. Therefore, the effects of D-004 (250 microg/mL), oleic (100
      microg/mL), lauric (50 microg/mL) or myristic (25 microg/mL) acids and their
      combined effects on phenylephrine (PHE: 10(-7)-10(-4) mol/L) induced contractions
      has been studied. No treatment changed the basal tone of the preparations, but
      all inhibited PHE-induced contractions. D-004 produced the highest inhibition,
      followed by lauric acid, which was more effective than myristic and oleic acids
      against PHE-induced contractions of control group. D-004 and the mixture of the
      three acids produced similar inhibitions.

PMID- 21941943
TI  - Effect of green tea (Camellia sinensis L.) extract on morphological and
      functional changes in adult male gonads of albino rats.
AB  - Green tea, prepared from the steamed and dried leaves of the shrub Camellia
      sinensis, is known for its antioxidant and anti-carcinogenic effects. However,
      its effects on male gonadal functions have not been explored adequately and the
      present investigation has been undertaken to evaluate the effect of green tea
      extract on gonads of adult male albino rats. Results of in vivo studies showed
      that green tea extract (GTE) at mild (1.25 g%, identical to 5 cups of tea/day),
      moderate (2.5 g%, identical to 10 cups of tea/day) and high (5.0 g%, identical to
      20 cups of tea/day) doses, for a period of 26 days, altered morphology and
      histology of testis and accessory sex organs. A significant dose-dependent
      decrease in the sperm counts, inhibited activities of testicular delta(5)3beta
      and 17beta-hydroxysteroid dehydrogenase (delta5-3beta3-HSD and 17beta3-HSD
      respectively) and decreased serum testosterone level were noticed. Significant
      increase in serum LH level was observed after moderate and high doses; serum FSH
      level also increased but not significantly. Histopathological examination showed
      inhibition of spermatogenesis evidenced by preferential loss of matured and
      elongated spermatids. Results of this study showed that GTE at relatively high
      dose may cause impairment of both the morphological and normal functional status
      of testis in rodents and thus its consumption at relatively high doses raises
      concern on male reproductive function in spite of its other beneficial effects.

PMID- 21941944
TI  - Analgesic activity of the aqueous seed extract of Hunteria umbellata (K. Schum.)
      Hallier f. in rodents.
AB  - The analgesic effect and possible mechanism(s) of action of 50-200 mg/kg of the
      aqueous seed extract of H. umbellata (HU) were investigated in different
      experimental models of analgesia using the tail flick, tail immersion, acetic
      acid-induced writhing tests and formalin-induced algesia. Oral pre-treatment with
      50-200 mg/kg of HU caused significant and dose related analgesic effect in the
      treated rats in all the experimental models used. This analgesia was mediated via
      central and peripheral mechanisms. Overall, the results showed that HU possesses
      analgesic effect which lends support to its folkloric use in the local management
      of pain.

PMID- 21941945
TI  - Protection against radiation clastogenecity in mouse bone marrow by Phyllanthus
      niruri.
AB  - The effects of aqueous (PnAq) and alcoholic (PnA1 extract (50-250 mg/kg) of P.
      niruri on in vivo gamma radiation induced chromosome aberration and in vitro
      antioxidant activity (50-500 microg/ml) were studied. The antioxidant activity
      was studied by measuring inhibition of hydroxyl radicals generated by the fenton
      reaction along with pro-oxidant and iron chelating ability. PnA1 showed highly
      significant in vitro free radical scavenging ability when compared to DMSO above
      250 microg/ml concentration. PnAq showed significant pro-oxidant activity while
      PnA1 was devoid of it at the tested concentrations. Exposure to gamma radiation
      (4 Gy) caused 29.10 % increase in the frequency of chromosomal aberrations.
      Administration of PnA1 (250 mg/kg) showed highly significant decrease in
      chromosomal aberrations compared to radiation treated group. Radioprotective
      potential of alcoholic extract was found to be more effective than the aqueous
      extract. Qualitative phytochemical investigation of PnAq and PnA1 revealed the
      presence of sugars, flavonoids, alkaloid, lignans, polyphenols, tannins,
      coumarins and saponins. Higher radioprotective effect of the alcoholic extract
      may be attributed to rich presence of antioxidant polyphenolic compounds.

PMID- 21941946
TI  - In vitro propagation and mass scale multiplication of a critically endangered
      epiphytic orchid, Gastrochilus calceolaris (Buch.-Ham ex J.E.Sm.) D.Don. using
      immature seeds.
AB  - In vitro asymbiotic seed germination potential of its immature seeds (36 weeks
      after pollination) of G. calceolaris was successfully tested on three different
      agar gelled nutrient media i.e. Murashige and Skoog (MS), Mitra et al. (M) and
      potato dextrose agar (PDA). Seeds germinated within 15.75+/-0.75 to 35.75+/-0.75
      days in the three different media. The protocorms developed therefrom
      subsequently differentiated into first leaf and root primordia, and complete
      seedlings were obtained within 111.25+/-1.25 to 141.25+/-1.25 days on MS and M
      media. The protocorms, though failed to differentiate further on basal PDA
      medium, despite repeated subculturings, incorporation of peptone (P; 1 gl(-1)),
      yeast extract (YE; 2 gl(-1)) and coconut water (CW; 20%) in the medium proved
      beneficial in inducing differentiation, in these germinating entities. Additional
      use of growth additives (P/YE/CW), in general, favoured better germination,
      protocorm formation and seedling development. The optimal nutritional combination
      during seed germination, protocorm growth and multiplication and seedling
      development was found to be CW (10%) enriched MS medium.

PMID- 21941947
TI  - Tuberculosis management--time for paradigm shift?

PMID- 21941948
TI  - FNAC in tuberculous lymphadenitis: experience from a tertiary level referral
      centre.
AB  - BACKGROUND: In developing countries like India, tuberculous lymphadenitis is one
      of the most common causes of lymphadenopathy. However, anti-tubercular treatment
      cannot be given only on clinical suspicion. Cytomorphology with acid fast
      staining proves to be a valuable tool in diagnosing these cases. AIMS: To study
      the utility, limitations of fine needle aspiration cytology and various
      cytomorphological presentations in reference to Ziehl-Neelsen staining in
      tuberculous lymphadenitis. MATERIAL AND METHODS: In a study period of July to
      October 2010, three hundred and eighteen consecutive superficial lymph nodes,
      clinically suspected to be tuberculous were subjected to cytological evaluation
      with Hematoxylin & Eosin, Giemsa and Ziehl-Neelsen stained smears. In addition,
      demographic profile of these patients with clinical presentation was also
      studied. RESULTS: Incidence of tuberculous lymphadenitis was 55%. Overall AFB
      positivity was 71.0%. Only Necrosis without epithelioid cell granulomas was the
      most common cytological picture and that showed highest AFB positivity also.
      Three-fourth of the patients presented in second to fourth decade of life.
      Cervical region was the most common site of involvement with solitary
      lymphadenopathy as the most common presentation in contrast to matted lymph nodes
      as reported by others. CONCLUSIONS: Fine needle aspiration cytology is a safe,
      cheap procedure requiring minimal instrumentation and is highly sensitive to
      diagnose tuberculous lymphadenitis. The sensitivity can be further increased by
      complementing cytomorphology with acid fast staining. In acid fast staining
      negative cases, yield of acid fast bacilli positivity can be increased by doing
      Ziehl-Neelsen staining on second smear or decolourized smear revealing necrosis
      or by repeat aspiration. Microbiological assessment should also be done in such
      cases.

PMID- 21941949
TI  - Correlation of sputum smear status with CD4 count in cases of pulmonary
      tuberculosis and HIV co-infected patients--a hospital based study in a rural area
      of Central India.
AB  - BACKGROUND: In HIV-infected patients, PTB (Pulmonary Tuberculosis) is still the
      commonest form of TB. The most cost-effective method of detecting TB cases among
      PTB suspects in high-prevalence countries is by sputum smear microscopy. World
      Health Organisation (WHO) states that sputum positivity decreases accompanying
      with atypical chest x-ray findings as CD4 count decreases. This expectation that
      infection with HIV would reduce the sensitivity of acid-fast smears, due to a
      decreased frequency of cavitary pulmonary MTB, has not been substantiated in a
      few studies done in the past. This study was undertaken to see the correlation of
      sputum smear status with CD4 count in cases of Pulmonary Tuberculosis HIV
      coinfected patients in our institute, being a tertiary referral centre.
      METHODOLOGY: In our hospital based cross-sectional study, 98 patients having PTB
      HIV co-infection were followed and acid fast smear positivity status was assessed
      in correlation with chest radiograph and CD4 count. RESULTS: Acid-fast smear
      positivity to negativity was almost 1:1 in CD4 count between 0-200 whereas it was
      3:1 in cases of CD4 count above 200. There was significant difference (p value
      0.013) in two groups with CD4 count cut-off value 200 which endorses the fact by
      WHO that sputum smear negativity increases with increase in degree of
      immunosupression. CONCLUSION: Sputum examination remains an important diagnostic
      tool for pulmonary tuberculosis in immunocompromised host with CD4 count above
      200 but there is an urgent need for better diagnostic methods in CD4 count below
      200.

PMID- 21941950
TI  - Proficiency panel testing--a reliable tool in external quality assessment of
      sputum smear microscopy services in Gujarat, India.
AB  - OBJECTIVE: To assess the proficiency of Senior TB Laboratory Supervisors (STLSs)
      and district level Laboratory Technicians (LTs) in sputum smear microscopy.
      METHOD: Intermediate Reference Laboratory (IRL), Ahmedabad had manufactured and
      validated Proficiency Panel Testing slides from sputum samples, made On Site
      Evaluation (OSE) visits of District TB Centres (DTCs) in two rounds, and
      conducted Proficiency Panel Testing of STLSs & DTC-LTs from January 2005 to June
      2009. RESULTS: High level of concordance in Z-N smear grading was found between
      Microbiologist and district laboratory staff. DTC readers reported overall
      consistency level of more than 98% in Z-N grade agreement during both the IRL,
      EQA, OSE visits. The tendency to over-grade the panel slides was much higher
      (more than 22%) as compared to under-grade (less than 2%) them in "correct
      slides". High False Positive (HFP) error was not observed in the present study.
      CONCLUSION: Laboratory supervisor's proficiency can be quickly assessed by
      Proficiency Panel Testing, under multi-level quality assurance network system of
      sputum smear microscopy in public health programmes like the RNTCP. Proficiency
      Panel Testing is highly replicable and reproducible tool for quick and reliable
      assessment of proficiency of the staff and it can be made more effective by
      raising the proportion of lower grade positive slides in panel set of each
      reader. DTC readers' overall agreement level of more than 98% in Z-N grade
      suggests high level of precision and excellent consistency during both the IRL,
      EQA, OSE rounds. It is concluded that even for a large network of sputum smear
      microscopy centres under public health programmes like the RNTCP in order to take
      corrective action, Proficiency Panel Testing can be effectively used for quick
      identification of suboptimal- technical performance of the supervisory staff.

PMID- 21941951
TI  - Role of endoscopic ultrasound guided FNAC in diagnosis of pancreatic TB
      presenting as mass lesion: a case report and review of literature.
AB  - A 24-year-old male patient presented with abdominal pain, obstructive jaundice,
      anorexia and weight loss. Ultrasound abdomen revealed pancreatic head mass with
      dilated common hepatic duct and intrahepatic bliliary radicles. CECT abdomen was
      suggestive of pancreatic head mass invading portal vein, splenic artery and
      hepatic artery. Provisional diagnosis of unresectable carcinoma head of pancreas
      was established. Endoscopic ultrasound (EUS) was done, which was also suggestive
      of pancreatic head mass infiltrating portal vein. EUS guided Fine Needle
      Aspiration Cytology (FNAC) was taken with an intent to obtain tissue diagnosis
      and to start palliative chemotherapy. EUS guided FNAC features were suggestive of
      tuberculosis (TB). Patient was started on anti-tubercular therapy, to which he
      responded and was cured. Pancreatic tuberculosis should be considered as a
      possibility, in pancreatic mass, especially in countries where TB is endemic and
      establishing its diagnosis with the aid of FNAC can save trauma of major surgery
      to the patient, which prompted us to report this case.

PMID- 21941952
TI  - Bilateral spontaneous pneumothorax in miliary tuberculosis.
AB  - Pneumothorax is a common complication in pulmonary tuberculosis that is usually
      seen with underlying cavitary lesion. However, it is uncommonly seen in patients
      with miliary tuberculosis. This communication describes bilateral spontaneous
      pneumothorax in an 18 years' old female patient having miliary tuberculosis.

PMID- 21941953
TI  - Tuberculous osteomyelitis of the bone flap following craniotomy.
AB  - A patient of tuberculous osteomyelitis of the bone flap following craniotomy for
      acute subdural hemorrhage which was treated at Surat Municipal Institute of
      Medical Education & Research (SMIMER) from June 2010 has been reported. This
      report emphasizes the fact that while treating osteomyelitis of bone flap
      following craniotomy, possibility of tuberculosis should be considered,
      especially in our country. Treatment wise, the disease responded readily to
      routine anti-tubercular chemotherapy.

PMID- 21941954
TI  - Status report on RNTCP.

PMID- 21941955
TI  - The role of surgery in the second relapse of epithelial ovarian cancer. Selection
      criteria, morbidity and survival outcome.
AB  - BACKGROUND: The aim of this study was to investigate the benefit of cytoreductive
      surgery (CS) and palliative surgery (PS) because of bowel obstruction in the
      second relapse (SR) in epithelial ovarian cancer. METHODS: A retrospective
      population-based study on recorded information from 490 consecutive patients
      treated at the Norwegian Radium Hospital during 1985-2001 for their SR. In all,
      80 had surgery, 28 and 52 of which had their tertiary surgery (TS) and secondary
      surgery (SS), respectively and 410 were treated with chemotherapy or other
      therapy. RESULTS: Median survival time (MST) was nine months for the last group.
      Complete optimal cytoreduction (COC) was achieved in 56% of the patients operated
      with CS. At SS and TS 33% and 38%, respectively, achieved COC. MST was 46 versus
      seven months for 0 versus > 2 cm residual disease. MST for the CS and PS was 31
      versus five months, respectively. Twenty-eight percent with CS experienced
      complications versus 42% with PS including two deaths. On univariate analysis
      initial stage, residual tumor at first relapse, residual tumor at SR, treatment
      free interval from primary treatment to first relapse (TFI 0-1), type of
      chemotherapy at SR, WHO performance status, ascites, elevated CA 125 values,
      number of lesions, localization of tumor and tumor size were found to be
      significant prognostic factors for survival in the surgery group. CONCLUSIONS:
      The combination of COC, TFI 0-1 > or = 24 months, CA 125 < or = 35, < or = 3
      tumor lesions and WHO 1 performance criteria identifies a group of patients with
      the best overall survival in SR.

PMID- 21941956
TI  - Neuroendocrine carcinoma of the uterine cervix: a single institution case review.
AB  - OBJECTIVES: To investigate the clinicopathologic features and prognostic factors
      of neuroendocrine carcinoma of the cervix (NECC). STUDY DESIGN: All patients with
      NECC diagnosed between January 1990 and December, 2007 identified from the tumor
      registry and gynecological oncology databases at McGill University Health Centre
      comprised this series. RESULTS: Eleven cases were encountered. Four patients were
      FIGO Stage Ib1, one Stage Ib2, one Stage IIa, and the other five were advanced
      stages (III or IV). Ten patients had marked lymph vascular space invasion.
      Metastasis to the pelvic or paraortic nodes was observed in eight patients. Seven
      patients were treated by surgery followed by adjuvant chemoradiation, another two
      had chemoradiation and the other two only received palliative treatments. The
      median survival was 18 months. All three long-term survival patients were Stage
      Ib1 without lymph node involvement. CONCLUSION: NECC is an aggressive tumor with
      poor prognosis, and only early stages are potentially curable.

PMID- 21941957
TI  - Predicting nedaplatin sensitivity of cervical cancer using the histoculture drug
      response assay.
AB  - PURPOSE: There are currently no clinically available chemosensitivity assays for
      cervical cancer. In this study we evaluated whether the histoculture drug
      response assay (HDRA) could be used to predict chemosensitivity to nedaplatin
      (NDP) in cervical cancer. METHODS: Fifty-four surgical specimens and biopsies
      from patients with squamous cell carcinoma of the cervix were tested with the
      HDRA. The results were used to calculate the concentration resulting in 50%
      inhibition of tumor growth (IC50). We then determined the cut-off concentration
      for NDP, and investigated the chemosensitivity of NDP for each patient. Moreover,
      the correlations between chemosensitivity and the clinical response of NDP
      containing chemotherapy, and the clinical outcomes of the patients with Stage I
      and II disease were also investigated. RESULTS: Fifty-one of 54 specimens (94.0%)
      were evaluable with this assay. The optimal cutoff concentration of NDP was
      determined to be 48 microg/ml. In 18 patients with measurable lesions, all nine
      patients in the high sensitive group by HDRA were judged as partial response (PR)
      to NDP containing chemotherapy. In contrast five of nine patients in the low
      sensitive group were classified as stable disease, and four were PR. The true
      positive rate was 100%, the true negative rate was 55.6%, and the accurate
      prediction rate was 77.8%. Furthermore, the disease-free survival of the high
      sensitive group tended to be better than that of the low sensitive group in the
      patients who received postoperative adjuvant chemotherapy with NDP. CONCLUSIONS:
      In the current study, the sensitivity of cervical tumors to nedaplatin was
      predicted by the HDRA.

PMID- 21941958
TI  - Ovarian germ cell malignancy: a heterogeneous tumour requiring supra-regional
      management.
AB  - BACKGROUND: Malignant ovarian germ cell tumours (GCT) are rare tumours with
      clinical and histological heterogeneity. Risk adapted treatment of these tumours
      is advocated. METHODS: We reviewed patients with malignant ovarian GCT managed by
      a single specialist during 1991-2009 at our institution. Clinicopathological
      features that may predict behaviour of the disease and disease outcomes were
      assessed. RESULTS: Thirty-four patients with a median follow-up time of 5.7 years
      were identified. The 10-year estimated survival rates were up to 80%; 8/13
      patients with Stage I disease were recommended active surveillance, of whom three
      relapsed and, one with an immature teratoma died. CONCLUSIONS: Ovarian GCT are
      potentially curable but appear to have a worse prognosis than their testicular
      counterparts. To improve expertise in the management of these complex tumours and
      optimise future management, a supra-regional service modeled on that used in the
      management of gestational trophoblastic disease is proposed.

PMID- 21941959
TI  - Association of the IGF-I promoter P1 polymorphism with risk of cervical cancer.
AB  - Human papillomaviruses (HPV16, HPV18, HPV31, HPV33) are etiological agents in the
      development of cervical cancer. HPVs infect epithelial cells and depend on
      epithelial differentiation for the completion of their life cycle. Insulin-like
      growth factor I (IGF-I) is a potent mitogen involved in the regulation of cell
      proliferation and apoptosis of many cell types including normal and transformed
      epithelial cells. Deregulation of IGF-I expression and action is linked to
      diverse pathologies including cancer. A polymorphism in the P1 promoter region of
      the IGF-I gene may directly influence its expression. Using the PCR-SSCP method
      and sequencing of DNA, we identified a single nucleotide polymorphism (SNP) at 
      383(C>T) position of promoter P1 of the IGF-I in 16% of the study HPV-positive
      women with precancerous and cancerous lesions. In vitro, we observed that the SNP
      at-383(C>T) site significantly increased the reporter gene expresion in the HepG2
      cell line, but not in the HeLa cell line relative to the wild type promoter. It
      suggests that the studied SNP can change expression of the IGF-I gene in distinct
      ways in different types of tissues. Deregulation of expression of the IGF-I gene
      can affect normal epithelium development and in case of HPV infection can
      potentially disrupt the virus life cycle and stimulate its passage into the
      oncogenic life cycle or persistent viral infections. Therefore, we propose that
      SNP C>T at the -383 position of P1 promoter may be one of the helpful prognostic
      markers in the diagnosis of cervical cancer development of women with persistent
      infection in the ectocervical epithelium. We have not found any association
      between the polymorphism CA repeats in the promoter P1 region of the IGF-I gene
      and suceptibility to HPV infection and cervical cancer development. The (CA)19
      allele was the most common in the study of this group of women.

PMID- 21941960
TI  - Hysteroscopic diagnosis of uterine sarcomas at the Department of Gynaecology,
      Sant Joan de Deu University Hospital.
AB  - Uterine sarcomas are rare and the clinical diagnosis of sarcoma is difficult.
      Diagnostic and surgical hysteroscopy is a minimally invasive outpatient procedure
      that makes an accurate diagnosis of malignant intrauterine pathology and could
      play a role in the diagnosis of the uterine sarcomas. Uterine sarcomas diagnosed
      at the Department of Gynecology of Sant Joan University Hospital by hysteroscopy
      between January 2004 and August 2010 are described. In this period 2,441
      hysteroscopies were performed; a total of 67 adenocarcinomas of the endometrium
      and five sarcomas were diagnosed by hysteroscopy. The data are presented with a
      review of the literature, focusing on the diagnostic value of hysteroscopy in
      these tumors.

PMID- 21941961
TI  - Femoral artery embolism in patients undergoing a laterally extended
      parametrectomy (LEP) procedure.
AB  - INTRODUCTION: Since 1993 an operative technique without adjuvant therapy
      (laterally extended parametrectomy, the LEP procedure) has been in use at our
      institution for the treatment of Stage IIB cervical cancer and for patients with
      pelvic lymph node metastases in Stages IA-IIA. Iliac/femoral artery embolic
      occlusion in the cohort of LEP operated patients was studied in an 11 years long
      period. METHODS: The LEP-Wertheim procedure was used in 320 patients between 1994
      and 2005. Embolic occlusion of the iliac and/or femoral arteries was detected in
      four out of 255 (1.6%) cases. Thrombectomy was done on one blood vessel in three
      cases, on both the deep and superficial femoral arteries in one case were
      executed to restore the vessel patency. RESULTS: Three out of four patients
      following external iliac/femoral artery emboli removal healed up without any
      arterial occlusion-related symptoms. In one case preventive fasciotomy was needed
      to treat tumescence of the legs. This patient developed transient peroneal palsy,
      which necessitated the use of plantar support for one month and physiotherapy for
      one year for gait rehabilitation. CONCLUSIONS: Embolus occlusion of the
      iliac/femoral artery during the LEP-Wertheim procedure was observed in 1.6% of
      cases. This complication has not been reported in the literature before in
      relation to radical surgery in cervical cancer. Operating teams using LEP
      operations should be aware of that risk, and should be prepared for treatment.

PMID- 21941962
TI  - Vaginal and pelvic recurrences in stage I and II endometrial carcinoma--survival
      and prognostic factors.
AB  - AIM OF THE STUDY: The analysis of prognostic factors and treatment outcomes in
      106 patients with Stage I and II endometrial carcinoma (EC) treated between 1980
      and 2005 in the Center of Oncology, Maria Sklodowska-Curie Memorial Institute,
      Kracow, Poland, who developed vaginal or pelvic recurrences. MATERIAL AND
      METHODS: The median age of patients was 61. Stage IB and IC of EC was diagnosed
      in 48 (45.3%) patients and Stage IIA and IIB in 58 (54.7%) patients. All patients
      were treated previously with surgery (TAH-BSO) and postoperative radiotherapy.
      There were 17 (16%) patients with vaginal vault recurrences, 30 (28.3%) with
      lower one-third vaginal recurrences, and 59 (55.7%) with pelvic recurrences.
      Palliative treatment (chemo- or hormonotherapy) or best supportive care only was
      undertaken in 53 (50.0%) patients. Radical treatment was conducted in 70.6%
      (12/17) of vault recurrences, 86.7% (26/30) of lower one-third vagina
      recurrences, and 25.4% (15/59) of pelvic recurrences, with surgery (4 patients),
      brachytherapy +/- chemotherapy (34 patients), and teleradiotherapy +/-
      chemotherapy (15 patients). RESULTS: The 5-year overall survival rate in the
      observed group was 17%. Five-year survival was 23.3% (14/60) for patients with
      KPS 60-70 vs 8.7% (4/46) with KPS 40-50, 25% (12/48) patients with Stage I EC vs
      10.3% (6/58) with Stage II EC, and 34% (16/47) patients with vaginal recurrence
      vs 3.4% (2/59) with pelvic recurrences. CONCLUSIONS: In the analyzed group of 106
      patients with Stage I and II EC, treated previously with surgery and
      postoperative radiotherapy, 5-year overall survival rate was low; in radically
      treated patients it was 42.1%, and 13.3% for vaginal and pelvis recurrences,
      respectively. Univariate analysis showed a statistically significant, unfavorable
      impact of KPS < 60, Stage II and recurrence pelvic. Cox multivariate analysis
      demonstrated that the only independent prognostic factor for 5-year overall
      survival was the site of recurrence.

PMID- 21941963
TI  - Comparison of different ovarian cancer detection algorithms.
AB  - The objective of the study was to evaluate the accuracy of a combined-two step
      ovarian cancer screening tool consisting of the ovarian cancer symptom index
      combined with either a risk of ovarian malignancy algorithm (ROMA) or a risk of
      malignancy index. MATERIAL AND METHODS: The case-control study consisted of 31
      patients with ovarian cancer, 30 patients with benign ovarian diseases and 27 age
      matched healthy controls. RESULTS: Sensitivity and specificity of the ovarian
      cancer symptom index among menopausal women were 84.6% and 52.9%, respectively.
      ROMA revealed the highest discriminative value when compared to others (AUC
      98.4%). When the cutoff level of 28 was applied for menopausal women, ROMA
      revealed sensitivity and specificity of 95.8% and 93.1%, respectively.
      CONCLUSIONS: The ovarian cancer symptom index could be used as the first step in
      ovarian cancer screening with subsequent application of ROMA as a second step
      screening tool. A larger sample size in both control and patient groups should be
      evaluated to reach clear conclusions.

PMID- 21941964
TI  - Prevalence of cervical intraepithelial neoplasia in patients with atypical
      squamous cells of undetermined significance from cervical pap smears in Beijing.
AB  - OBJECTIVES: To determine the prevalence and factors associated with histologic
      diagnoses of cervical intraepithelial neoplasia in women with ASC-US. METHOD:
      Sampling investigations were carried out on married women aged 25-54 in 12
      districts in Beijing from April 2007 to November 2008. Further examinations and
      analyses were carried out on women with ASC-US in the cytological screening.
      RESULTS: Of 6,339 women, 9.6% suffered from cervical abnormalities in cytology;
      among them, 409 cases were ASC-US. Of the 409 ASC-US, 42.1% showed inflammation;
      50.9% had CIN 1, 6.1% had CIN 2, and three cases had CIN 3, one of which was
      cervical cancer. Four hundred and four cases were subjected to detection for the
      human papillomaovirus (HPV) and the infection rate was 30.7%. Morbidity in the
      HPV infected patients that suffered from CIN 2 or higher was significantly higher
      than that in the uninfected population (chi2 = 26.685, p = 0.000). No statistical
      significance was found in the correlation between the pathological results of ASC
      US and the loading dose of HPV infection (chi2 = 7.754, p = 0.458). CONCLUSION:
      The morbidity of CIN in women with ASCUS in Beijing is high, and women with ASC
      US should be paid great attention, especially women who are infected with high
      risk HPV.

PMID- 21941965
TI  - Surgical treatment of ovarian cancer and early detection of venous
      thromboembolism.
AB  - INTRODUCTION: Deep vein thrombosis (DVT) is present in 10.6% patients after
      operative treatment for ovarian malignancy. We undertook the present study to
      find the risk factors for venous thromboembolism (VTE) after surgical treatment
      for ovarian cancer and to clarify the prognostic value of D-dimer and a positive
      PTP test (Wells score) in these patients. MATERIAL AND METHODS: A total of 31
      consecutive patients with histologically confirmed ovarian cancer after surgery,
      clinically suspicious for DVT were followed from January 2006 to December 2008.
      All patients were operatively treated at the Clinical Center of Serbia. Study
      variables included age, cardiovascular disease, FIGO stage, histology, BMI,
      presence of massive ascites and tumor size, D-dimer level and Wells score. All
      patients were postoperatively administered anticoagulant therapy. RESULTS: DVT
      was found in nine of 31 patients (29.0%). High BMI and presence of massive
      ascites were significantly associated with DVT. D-dimer (DD) levels were high in
      27 of out 31 patients (87.1%). Sensitivity, specificity, positive predictive
      value (PPV) and negative predictive value (NPV) were 100, 18.2, 33.3 and 100%.
      Results of the PTP test (according to Wells score) was positive in 20 out of 31
      patients (64.5%). PTP score was not significantly different in patients with or
      without VTE (p = 0.606). Sensitivity, specificity, PPV and NPV were 66.7, 36.4,
      30.0 and 72.7%, respectively. CONCLUSION: Incidence of VTE after gynecological
      operations for ovarian cancer in our study was similar to other investigators.
      Obesity and the massive ascites are statistically significant risk factors.
      Measurement of DD level and ultrasonography could become the standard in
      predicting VTE in ovarian cancer surgery. The use of Wells score is not
      satisfying in these patients. Prediction of VTE after gynecological surgery needs
      further confirmation in randomized controlled trials.

PMID- 21941966
TI  - Intestinal surgery in treatment of advanced ovarian cancer--review of our
      experience.
AB  - INTRODUCTION: In cases of advanced ovarian cancer bowel surgery is necessary
      during the primary surgical procedure, in the course of the disease for
      recurrence or palliation of the symptoms. Treatment with maximal cytoreductive
      surgery followed by chemotherapy in women with advanced ovarian cancer is well
      established. MATERIAL AND METHODS: We retrospectivly evaluated 56 women who were
      surgically treated for ovarian cancer over five years (from 2004 to 2008) at the
      Institute of Obstetrics and Gynecology, Clinical Center of Serbia. In 56
      patients, 82 intestine operations were performed, which means that in some
      patients more than one intestine operation was performed. We analyzed patient
      characteristics, tumor features, intraoperative findings, pelvic node
      involvement, surgical procedure performed, indications for bowel surgery, and
      early postoperative complications. RESULTS: In our study the majority of patients
      had Stage III (82%) or IV (10%) carcinoma with poor differentiation. Epithelial
      ovarian cancer was the most common histopathological finding (78%) in our group
      of patients. There were 30 cases (53%) with serous, nine (16%) with mucinous and
      five (9%) with endometriod tumors. Bowel surgery was indicated in 12.2% of our
      patients with ovarian cancer which was mostly performed to reduce the volume of
      the tumor (68%), while it was indicated in recurrence of the disease in 18% of
      women. In addition to the standard surgery procedure, which includes removal of
      internal genital organs, omentum minus/majus, peritoneal tumor masses, large and
      small bowel resection were performed. Of 56 patients most underwent small bowel
      surgery--43 of a total of 82 intestinal operations (52.4%). Of these we performed
      small bowel resection in 34 (41.5% of all intestinal operations), while ileostomy
      and jejunostomy were performed in nine cases (11%). There were 39 colon
      operations (47.6%) and most of the cases underwent rectosygmoid resection with
      the Hartman procedure (33 or 40.2% of all intestinal operations). Other colon
      operations included hemicolectomy (3 cases--3.7%), transverse colon resection (2
      cases--2.4%) and pancolectomy (1 case--1.2%). According to our experience, wound
      infection and febrile morbidity were the most common early postoperative
      complications. Mortality rates in the literature vary between 0% and 8%, and
      anastomotic complications between 0 and 4%, which is in agreement with our
      results. CONCLUSION: Radical surgical procedures in treatment of ovarian cancer
      including multi-organ resection are necesery to achieve a minimal residual
      disease state prior to initiating adjuvant chemotherapy. Bowel preparation and
      CT/MR imaging should be performed in patients with possible malignant ovarian
      masses.

PMID- 21941967
TI  - A case of recurrent vulvar carcinoma treated with erlotinib, an EGFR inhibitor.
AB  - BACKGROUND: There is no effective therapy for patients with regional and/or
      distant recurrence of vulvar carcinoma. Recently two case reports about the use
      of erlotinib, an EGFR (epithelial growth factor receptor) inhibitor, in the
      context of recurrent vulvar cancer were published with a good clinical response
      reported. CASE: We report a case where erlotinib was used in a 67-year-old
      patient with recurrent and multi-treated vulvar carcinoma. Utilization of
      erlotinib was started with rapid clinical improvement. The treatment was well
      tolerated with palliation of symptoms. A CT scan also showed cutoff "net"
      improvement, with regression of size and number of hilar and pulmonary
      metastases. After one month of improvement, despite continuous treatment with
      erlotinib, dyspnea returned. A new CT scan showed an increased number of hilar
      nodes, a new hepatic lesion and increase in the size of the known pelvic lesion.
      CONCLUSION: EGFR inhibitors appear to be promising agents for this devastating
      and fatal disease. As with other studies with these agents, our patient showed a
      rapid response with important palliation of symptoms, however of short duration.

PMID- 21941968
TI  - Primary ovarian choriocarcinoma presenting with acute abdomen mimicking an
      ectopic pregnancy.
AB  - A young lady presented with signs and symptoms of ectopic pregnancy. Initial BhCG
      was 1110.5 IU/l dropped to 18.5 IU/l postoperatively. Ovarian biopsy taken at the
      time of laparoscopy confirmed the diagnosis of ovarian choriocarcinoma.

PMID- 21941969
TI  - Pleomorphic adenoma of the breast initially misdiagnosed as metaplastic carcinoma
      in preoperative stereotactic biopsy: a case report and review of the literature.
AB  - Pleomorphic adenoma (PA) is a benign mixed tumor found commonly in the salivary
      glands but rarely in the breast. PA might be misinterpreted clinically and
      pathologically as a malignant tumor. The differential diagnoses include
      fibroadenoma, phyllodes tumor and metaplastic carcinoma. Metaplastic carcinoma is
      the most important entitiy with respect to differential diagnoses, as surgical
      overtreatment, i.e., mastectomy may be the result. We describe one of the first
      cases of PA initially misdiagnosed as metaplastic carcinoma (osteoid-chondroid
      type) in a preoperative stereotactic biopsy and review the literature regarding
      this entity.

PMID- 21941970
TI  - Pitfall in the diagnosis of endometrial cancer: case report of an endometrioid
      adenocarcinoma arising from uterine adenomyosis.
AB  - BACKGROUND: The development of cancer from adenomyotic foci is a rare occurrence.
      The diagnosis is frequently delayed because of the absence of tumor in the
      eutopic endometrium. CASE REPORT: We present a case of a 64-year-old
      postmenopausal woman with irregular vaginal bleeding and dull abdominal pain.
      Hysteroscopy was negative and hormonal treatment was continued. Nine months
      later, persisting symptoms necessitated endometrial biopsy revealing an atrophic
      endometrium. Hydrosonography suggested an endometrial polyp of 14 x 7 mm with a
      surrounding regular thin endometrium and a diffusely inhomogeneous
      ultrasonographic pattern throughout the myometrium. Hysteroscopic excision of the
      endometrial polyp was performed. Biopsies obtained during operative hysteroscopy
      showed a well differentiated endometrioid endometrial carcinoma. A
      laparoscopically assisted vaginal hysterectomy with bilateral salpingo
      oophorectomy, pelvic lymphadenectomy and peritoneal cytology was performed.
      Pathologic examination revealed an atrophic endometrium and a Stage IB (FIGO
      2009) well differentiated endometrioid endometrial carcinoma with prominent
      squamous differentiation originating from nodular adenomyosis. This ectopic
      localization of the endometrioid carcinoma added to a diagnostic delay of 12
      months. CONCLUSION: Endometrial cancer arising from uterine adenomyosis may be
      difficult to diagnose. Awareness of this entity and careful ultrasonography are
      likely to reduce diagnostic delay.

PMID- 21941971
TI  - Primary granulocytic sarcoma of the breast: a case report and review of the
      literature.
AB  - Primary granulocytic sarcoma is an uncommon entity that rarely presents in the
      breast. It is frequently misdiagnosed as carcinoma or lymphoma and a broad panel
      of immunohistochemical markers including epithelial and haematological markers
      are essential for an accurate diagnosis. We reviewed all the cases of
      granulocytic sarcoma reported in the English literature since 1970 and present a
      new case of granulocytic sarcoma of the breast. Systemic chemotherapy for acute
      myeloid leukemia (AML) appears to be superior to surgery or radiotherapy.
      Granulocytic sarcoma should be in the pathologic differential diagnosis of a
      breast mass.

PMID- 21941972
TI  - Atypical ultrasonographic presentation of ovarian vein thrombosis.
AB  - Ovarian vein trombosis (OVT) is a pathologic entity classically considered as a
      postpartum complication and only rarely associated with other diseases. Due to
      its vague symptoms, it is usually underdiagnosed. However its consequences can be
      fatal. We report a case of an incidental finding of ovarian thrombosis in an
      asymptomatic 45-year-old woman who underwent surgery due to the ultrasonographic
      finding of a para-ovarian cyst.

PMID- 21941973
TI  - Primary ovarian non-Hodgkin's lymphoma.
AB  - BACKGROUND: Primary ovarian non Hodgkin's lymphoma (PONHL) is a very rare
      disease. We present a case of PONHL and review the literature. CASE: The patient,
      a 24-year-old nulliparous Greek woman, presented with the complaint of abdominal
      pain. She underwent left salpingo-oophorectomy, multiple biopsies from the right
      ovary, total omentectomy, pelvic and paraortic lymphadenectomy, appendectomy and
      curettage. The histopathology revealed diffuse large B-cell non-Hodgkin's
      lymphoma of the left ovary. She underwent postoperative chemotherapy. She remains
      well without evidence of disease, 15 months after initial surgery. CONCLUSION:
      The use of chemotherapy is based on the principle that PONHL must be considered a
      localized manifestation of systemic disease. Patients with PONHL have a similar
      outcome compared to patients with other NHL.

PMID- 21941974
TI  - Rectal cancer in pregnancy: a case report.
AB  - Rectal cancer in pregnancy is a rare but a life-threatening disease. This paper
      presents a case of rectal cancer in pregnancy, discussed in light of the
      literature.

PMID- 21941975
TI  - Parovarian tumors of borderline malignancy.
AB  - The incidence of a parovarian tumor is 10-20% of all uterine adnexal masses,
      however, it is benign in most cases, and a borderline or malignant tumor is
      extremely rare. The classification of disease stage and treatment is still
      controversial owing to its scarcity. We have managed one mucinous and two serous
      cystadenomas of borderline malignancy originating from paraovarian cysts in our
      institute over ten year. We report and discuss the cases herein.

PMID- 21941976
TI  - Primary malignant melanoma of the uterine cervix--case report and review.
AB  - INTRODUCTION: Malignant melanoma (MM) represents 1% of all cancers and has an
      incidence of 3-7% in the female genital tract, the majority of cases being
      reported in the vulva and vagina. CASE REPORT: A 75-year-old white female had a
      history of vaginal bleeding due to a 1.5 cm exophytic and ulcerated cervical
      lesion. Incisional biopsy was taken and sent for histopathological examination,
      which revealed MM of the cervix, confirmed by immunohistochemistry. Exclusion of
      the primitive tumor in other sites was made and after FIGO staging (IB1) the
      patient underwent a radical hysterectomy with bilateral salpingo-oophorectomy and
      pelvic lymphadenectomy. Three months later, hepatic and osseous metastases were
      detected, and the patient underwent chemotherapy and palliative radiotherapy with
      no success. DISCUSSION: Primary MM of the cervix should be considered in the
      differential diagnosis of cervical malignancies. Early diagnosis is essential in
      order to warrant a better prognosis, although there are no cases of cure
      described.

PMID- 21941977
TI  - Endometrial carcinoma and ovarian sex cord tumor with annular tubules in a
      patient with history of Peutz-Jeghers syndrome and multiple malignancies.
AB  - BACKGROUND: Peutz-Jeghers syndrome is a rare syndrome which is inherited in a
      dominant manner. It is characterized by hamartomatous polyps of the
      gastrointestinal tract, hyperpigmented macules of the oral mucosa and an
      increased risk of developing neoplasms in the gastrointestinal tract, pancreas,
      breast and genital system. Women with Peutz-Jeughers syndrome often develop an
      ovarian sex cord tumor and cervical adenocarcinoma of minimal deviation adenoma
      malignum type. A case of a 58-year-old patient with Peutz-Jeghers syndrome and
      history of multiple malignancies (thyroid, breast and colon cancer) who presented
      with metrorrhagia is reported. The dilatation and curettage revealed endometrial
      adenocarcinoma. The patient underwent total abdominal hysterectomy with bilateral
      oophorectomy. The histologic examination showed an endometrioid endometrial
      adenocarcinoma that developed in atypical endometrial hyperplasia. The histologic
      examination of the right ovary revealed a sex cord tumor with annular tubules,
      measuring 3 cm. Sex cord tumors with annular tubules in patients with Peutz
      Jeghers syndrome are usually small, bilateral tumors of the ovaries which have
      common characteristics with granulosa cell tumor and Sertoli cell tumor.
      Hyperestrogenism is a rather common finding with development of estrogen
      dependent lesions.

PMID- 21941978
TI  - Adenomyoma associated with high level of CA 125 and CA 19-9: case report.
AB  - PURPOSE OF INVESTIGATION: A rare case of increasing CA 125 and CA 19-9 levels
      increasing in a woman with adenomyoma is described. METHODS: A 39-year-old
      nullipara woman with CA 125 = 1,796 U/ml and CA 19-9 = 177 U/ml was submitted to
      abdominal and pelvic MRI, gastric endoscopy, colonoscopy, hysteroscopy, pelvic
      Doppler and PET scan. None of the exams revealed any apparent malignant disease.
      RESULTS: Six months of gonadotropin releasing hormone agonist treatment reduced
      CA 125 and CA 19-9 levels. However, after contraceptive pill use the markers were
      again elevated, and a laparoscopic hysterectomy was performed, and normal CA 125
      and CA 19-9 levels were achieved. CONCLUSIONS: Adenomyoma may be associated with
      high levels of CA 125 and CA 19-9.

PMID- 21941979
TI  - Borderline micropapillary serous tumor of the ovary detected during a cesarean
      section due to a transabdominal cervico-isthmic cerclage in a patient with
      congenital cervical hypoplasia: a rare case.
AB  - A young woman with polycystic ovary syndrome and congenital cervical hypoplasia
      conceived with clomifen citrate treatment after placement of a transabdominal
      cervico-isthmic cerclage. Her pregnancy successfully reached term and cesarean
      section was performed to preserve the cerclage for the next pregnancy; when the
      ovaries were explored an irregular structure was detected on the left ovary. A
      wedge biopsy was done and the pathological assessment of the specimen was
      borderline micropapillary serous tumor of the ovary. The patient wanted to
      preserve her fertility, therefore a fertility-sparing staging surgery was
      performed six months after the cesarean section. There was no residual tumor in
      the left ovary, but there was a borderline tumor in the right ovarian biopsy
      specimen (frozen section was negative). Two months after staging surgery the
      patient conceived with IVF and delivered twins at the 33rd week of pregnancy with
      cesarean section. At her second cesarean section the right ovary and abdomen
      appeared normal on inspection, but the cerclage tape was in the endocervical
      canal and was thus removed. To our knowledge this is the second reported case of
      transabdominal cerclage tape migration into the endocervical canal. The patient
      is clinically disease-free 18 months after her second cesarean section. The
      clinical findings, treatment modalities, management and prognosis are discussed
      together with a literature review of a patient with a serous borderline ovarian
      tumor and congenital cervical hypoplasia.

PMID- 21941980
TI  - Intestinal surgery and surgery of urinary tract in treatment of recurrent
      cervical cancer--case report.
AB  - A case of a 31-year-old patient admitted to the Institute with a diagnosis of
      recurrent cervical cancer after radical hysterectomy and radiation therapy 12
      months before. The patient had intestinal and urinary obstruction and also the
      tumor compressed the iliac blood vessels superficially. She underwent clinical
      examination, pelvic and abdominal ultrasound and multislice CT scan. A recurring
      tumor with a diameter of 7 cm was diagnosed. It was localized in the left
      parailiac and obturator region and infiltrated the left ureter, left bladder side
      wall, sigmoid colon and iliac blood vessels superficially. The patient had left
      pelvic sidewall relapse, so she underwent a palliative surgical procedure. We
      evacuated the complete tumor together with the infiltrated parts of the left
      ureter, sigmoid colon and bladder. At the end of operation left
      ureterocystoneostomy was performed as well as the Hartmann procedure with anus
      praeter insertion. There were no significant postoperative complications. After
      the surgical treatment of the recurrence, we suggested that the patient continue
      treatment of her disease with chemotherapy.

PMID- 21941981
TI  - [Abstracts of the 4th Psychiatric Meeting, 150 years of thermalism at Saujon, 24
      25 September 2010].

PMID- 21941982
TI  - What is a diplomate?

PMID- 21941983
TI  - Clinical roundtable monograph: new and emerging treatments for advanced prostate
      cancer.
AB  - Historically, the treatment of metastatic castration-resistant prostate cancer
      (CRPC) has been limited to chemotherapeutic regimens that did not improve patient
      survival. In 2004, clinical studies began to demonstrate significant improvements
      in patient outcomes, including overall survival, with docetaxel versus
      mitoxantrone chemotherapy. Since these pivotal trials, the combination of
      docetaxel plus prednisone has become a standard of care for patients with
      metastatic CRPC. However, the limited survival benefit achieved with this regimen
      prompted several investigations into the development of alternative therapeutic
      options. Recent advances have now led to an unprecedented number of new drug
      approvals within the past year, providing many new treatment options for patients
      with metastatic CRPC. Sipuleucel-T, considered a new paradigm in cancer
      treatment, is the first such immunotherapeutic agent approved by the US Food and
      Drug Administration. Other successes include abiraterone acetate, the first
      androgen biosynthesis inhibitor, and cabazitaxel, a novel microtubule inhibitor,
      both of which have demonstrated improved survival following docetaxel failure.
      The bone-targeting agent denosumab, also recently approved in this setting,
      offers these patients significant improvement in the prevention of skeletal
      related events. The data supporting the approval of each of these agents are
      described in this monograph, as are current approaches in the treatment of
      metastatic CRPC and ongoing clinical trials of novel treatments and strategies.
      The experts also discuss several of the issues regarding the introduction of
      these novel agents into clinical practice for metastatic CRPC patients.

PMID- 21941984
TI  - [The Roman lady-doll: a surprising image of the female body].
AB  - Ivory or bone lady-dolls found in Italy and in the Western empire, from the 2nd
      to the 5th century, seem to be erotic toys, with a beautiful hair-dress,
      articulated body, and riche jewels, strange presents to be given to little girls
      or young ladies. Archaeological and epigraphical documents, literary texts, and
      present Barbies are put together.

PMID- 21941985
TI  - [The female world in the Necropolis in Castellaccio (Rome, IV cent. B.C., IV
      A.C.)].
AB  - The archaeological investigation carried out from 2003 in the Castellaccio
      locality, undertaken to realize the "Europarco" town planning, brought to light a
      part ofa road dated to the roman age, identified as the ancient via Laurentina.
      The road is oriented N/NE-S/SW, is 400 metres long and cross with a bridge the
      Fosso dell'Acqua Acetosa. Two buildings run alongside this trait of the ancient
      Laurentina: one can be interpreted as a rural structure, the other one as a
      mansio. A sidestreet starts from the final edge of the recovered road and run
      toward East, along the original route of the Fosso dell'Acqua Acetosa Ostiense:
      the historians recognized it as a boundary of the Ager Romanus Antiquus nearby
      the VI mile, place of the god Terminus sanctuary. A necropolis made up ofmore
      than 130 graves, mainly inhumations, was found in the southern part of the
      crossroads, near the oriental side of the Laurentina. The stratigraphical
      analysis and the examination of the grave goods allowed the characterization of
      three period of funerary use of the necropolis, between the middle republican age
      and the first two century of the Empire. In all three period stand out graves of
      infants and women, of extreme interest from the ritual point of view and supplied
      with rich grave goods.

PMID- 21941986
TI  - [A space for women in the Etruscan and Roman houses (VI-I cent. B.C.)?].
AB  - The article analyzes the scientific discussion about the existence of a domestic
      space reserved to women in Etruscan and Roman houses. The hypotesis regarding the
      existence of a 'gynaeceum' has been recently proposed for the Etruscan houses
      built on Palatino in Rome (VI cent. B.C.) and for the ancient phase of the
      Centaurus Protodomus in Pompei. Considering the specific role of Roman matronae
      as laniferae, and also a substantial equality of social role between Etruscan men
      and women, it is possible to advance the hypotesis of the existence of a room
      originally reserved to women (oecus) on one side of the tablinum, the symmetrical
      room being reserved to men (triclinium).

PMID- 21941987
TI  - [How Augustae women are perceived in everyday life].
AB  - We basically have a double portrait ofAugustae women, which means those who
      belonged to domus Augusta. Ancient historians mostly describe them as thirsty of
      power and obsessed by sexual desire. Whereas the coins, the iconography and the
      official inscriptions gave us a propagandist image, focused especially on the
      fact that the Augusta is supposed to give an heir to the Emperor. The purpose of
      this work is to analyze the Augustae's eventual "popular" success. In order to do
      it, it was firstly catalogued all the epigraphic material useful for this type of
      research. These inscriptions are not many and, at present state of the research,
      they let us analyze the popular favour of two Augustae: the acclamations written
      on Pompei walls for Poppea, Nerone's wife, and Faustina Minore's role as marriage
      guarantor and protector.

PMID- 21941988
TI  - [The necklace from the 660 grave in Megara Iblea].
AB  - The article analyzes the 660 grave in Megara Iblea, a Greek colony in Sicily, in
      which a woman has been buried. On her breast a magnificent neckless was found,
      made of amulets recalling the travel of the sun during the summer solstice. Some
      objects allude to solar cults (a cock; round pendants), others seem to came from
      Gallia and Macedonia (summer far West and East), others recall archeological
      contexts such as tombs in Marvinci, in the Vardar Valley, and allude to relations
      with female practices of medicine and magic and to female roles characterized by
      extraordinary powers, due to being descendants of the Sun god. These solar
      symbols, joint with the discovery of many little objects, typical of children
      burials, allow to hypotize a relation with the cult of Mater Matuta and seem to
      point out a difficult or anomalous pregnancy or birth.

PMID- 21941989
TI  - [Women in Francavilla Marittima (CS) between indigenous world and the Greek
      city].
AB  - Francavilla Marittima is a protohistorical site; its ancient traces dates from
      the Medium Bronze Age. The article examines two female graves in the Temparella
      Cairn, collecting 93 graves from VIII to VI cent. B.C.. Grave n. 8 preserved a
      rich female set (i.e. a loom weight; a ceramic pix; a portable kotyle), made of
      imported and 'masculine' objects, here intended for a female use. Grave n. 26 is
      characterised by a great number of vases, turned upside-down to cover the body of
      a woman. This particular burial modality recalls the religious cerimonies of
      Demeter in Gela; it probably alludes not to a social role (a women seller of
      vases? An 'object' between objects?) but to the specific role of the dead inside
      a female cult.

PMID- 21941990
TI  - [Female anthropology, physiology and disease in ancient Christian writers].
AB  - Ancient Christian sources are rich in reference to the anthropology and
      physiology of the female. Christianity in the first centuries had multiple
      positions as concerns the doctrinal thoughts as well as the social practices.
      Christian anthropological doctrine has been developed along two exegetical lines,
      hinging on Genesis 1-3: the first views the human being as a whole psycophysical
      entity and thereby highlights the protological inferiority of the woman; the
      second, spiritual and Platonic, emphasizes the inner self and thus, in theory, is
      more equalitarian. Ancient philosophical theories regarding human generation, in
      particular those ofAristotle and the Stoics, are used, along with medical
      notions, by Christian theologians to elaborate the dogma of incarnation. However,
      in certain cases, as with the post partum virginity of Maria, medical theories
      are totally put aside. The stories recounting the miracles offer the possibility
      of understanding medical practices offemale conditions and the emotive reactions
      of the women.

PMID- 21941991
TI  - Representations and realities: cemeteries as evidence for women in Roman Britain.
AB  - The article considers how burial evidence might contribute to the undestarnding
      of gender, i.e. the socio-cultural construction of sexual difference, as a
      dynamic aspect of identity in a Roman province, with a particular focus on women.
      This subject has hitherto received limited attention and its potential is too
      great to explore fduly in a short paper. Given this costraint, the article
      indicates possibilities and problems rather than to offer definitive conclusions.
      Its emphasis lies on Roman Britain, but similar questions could be applied to
      other parts of the Roman world.

PMID- 21941992
TI  - [Female funerary contexts in the Ostiense suburbium: new data].
AB  - This work concern severalfindings of the last years infunerary contexts in the
      Ostiense suburbiums, during archaeological investigations carried out by the
      Soprintendenza Archeologica of Ostia. The latest excavations provided new data to
      understand the width of the vast funerary area, that probably extended
      uninterruptedly from East to South of the ancient city of Ostia. New evidences
      about the funerary rituals came to light, and emerged first anthropological data
      referred to inhumated and cremated people from Ostia. The results, compared with
      those obtained from the numerous Rome's necropolis, bring to a preliminary
      reconstruction of the burial practices in a territory directly connected with
      Rome, where are reported female's graves of extreme archaeological and
      anthropological interest.

PMID- 21941993
TI  - [Necropolis in Castellaccio, tomb n. 116].
AB  - The article analyzes the grave goods contained in the tomb n. 116 in the
      Necropolis of Castellaccio in Rome (IV Cent. B.C.-IV cent. A.C.) and offers a
      description of a bracelet and some rings, analyzed by electronic microscope and
      by EDS.

PMID- 21941994
TI  - The continued rise of respiratory viruses.
AB  - Respiratory viral illness ranges from trivial to fatal. Testing is indicated only
      in a minority. The decision to test is based on clinical presentation, available
      resources, and the clinician's philosophy. Flocked swabs are easier to obtain
      than aspirates and perform similarly. Commercially available room-temperature
      transport media perform well and should be used with both swabs and aspirates
      sent for PCR testing. Nucleic-acid-amplification techniques are preferred to
      immunochromatographic antigen tests but are less widely available and take
      longer. Immunochromatographic antigen tests should not be used if prevalence is
      low. The development of novel antiviral agents will tend to increase viral
      testing and cost containment measures to decrease it. Overall, testing for
      respiratory viruses is likely to increase.

PMID- 21941995
TI  - Where is that specimen?

PMID- 21941996
TI  - Roundup: the right tests for your lab.

PMID- 21941997
TI  - Coaching helps build great teams.

PMID- 21941998
TI  - Phlebotomy training: does your program pass the test?

PMID- 21941999
TI  - Needlestick statistics drop as passive safety device use rises.

PMID- 21942000
TI  - Protection against needlestick injuries: active or passive safety?

PMID- 21942001
TI  - The health crises of chronic pain and prescription drug misuse.

PMID- 21942002
TI  - A retiree's perspective.

PMID- 21942003
TI  - The decline of traditional health care marketing.

PMID- 21942004
TI  - Rehabilitation at work.
AB  - As increased opportunities for consumers to directly access health care providers
      continue, clinicians and their professional associations are progressively
      utilizing marketing and communications to showcase their capabilities and
      relevance. In 2007, the American Physical Therapy Association-which represents
      more than 77,000 member physical therapists, physical therapy assistants and
      students-embarked on a multi-year initiative to elevate the profession. APTA
      partnered with public relations and marketingfirm CRT/tanaka to conduct a
      comprehensive study to determine how patients and prospective patients view
      physical therapists, and to develop and implement a new branding strategy.

PMID- 21942005
TI  - As you look over your career, what health care marketing initiative that you
      worked stands out and why?

PMID- 21942006
TI  - GPS for the social media superhighway.

PMID- 21942007
TI  - Marketing to the rescue.

PMID- 21942008
TI  - Prognosis: convenience.

PMID- 21942010
TI  - Words to live by.

PMID- 21942009
TI  - Painting the town red.

PMID- 21942011
TI  - Finding nirvana: patients loving and trusting our hospitals.

PMID- 21942012
TI  - [Study on the movement of the carrier recombination region in organic light
      emitting diodes (OLEDs) based on DPVBi/Alq3].
AB  - Series of organic light emitting devices with basic structure of ITO/PCBM: PVK(x
      Wt%, approximately 40 nm)/DPVBi(30 nm)/Alq3 (30 nm)/Al were fabricated in order
      to investigate the carrier recombination region movement in these devices. The
      carrier injection-dependent, the carrier transport-dependent and the voltage
      dependent carrier recombination region movements were investigated respectively
      by modifying cathode with lithium fluoride, by changing the doping concentration
      of PCBM and by changing the voltage on the devices. The physical mechanism behind
      the voltage-dependent carrier recombination region movement was discussed.

PMID- 21942013
TI  - [Synthesis, crystal structure and luminescent properties of a dysprosium
      coordinaation polymer based on pyridine-2, 6-dicarboxylic acid].
AB  - 2-D layered Dy coordination polymer [Dy(PDA) (HPDA)I]n (1)(H2PDA = pyridine-2,6
      dicarboxylic acid) with (4.8(2)) topological network was synthesized under
      hydrothermal conditions and was characterized by elemental analysis, IR spectrum,
      and single-crystal X-ray diffraction. X-ray diffraction analysis reveals that
      compound 1 is monoclinic, space group P2(1)/c. In the structure of compound 1,
      metal-centered Dy is connected via O atoms of H2PDA ligands to form a (4.82)
      topology network. The 3-D supramolecular structure of 1 is constructed through pi
      -pi stacking interactions between the adjacent layers. The luminescence
      properties of 1 were determined by UV-Vis and fluorescence spectrum in solid
      state at room temperature. The H2PDA and 1 exhibit the similar broad maximum
      absorption peak at 280 nm, which are attributed to ligand-centered pi--pi*
      transition. The fluorescence emission band based on ligand-center and
      characteristic emission of Dy3+ at the same maximum excitation wavelength of 280
      nm were observed in 1. The fluorescence decay curve of complex 1 indicated that
      the processes of decay consists of two components, of which corresponding
      lifetimes tau1 = 3.61 micros and tau2 = 12.81 micros.

PMID- 21942014
TI  - [Research on the photoelectric conversion efficiency of grating antireflective
      layer solar cells].
AB  - A numerical investigation of the effect of grating antireflective layer structure
      on the photoelectric conversion efficiency of solar cells was carried out by the
      finite-difference time-domain method. The influence of grating shape, height and
      the metal film thickness coated on grating surface on energy storage was analyzed
      in detail. It was found that the comparison between unoptimized and optimized
      surface grating structure on solar cells shows that the optimization of surface
      by grating significantly increases the energy storage capability and greatly
      improves the efficiency, especially of the photoelectric conversion efficiency
      and energy storage of the triangle grating. As the film thickness increases,
      energy storage effect increases, while as the film thickness is too thick, energy
      storage effect becomes lower and lower.

PMID- 21942015
TI  - [Luminescence of Sr2Mg(BO3)2:Tb3+ under vacuum ultraviolet excitation].
AB  - The phosphors of Tb3+ activated Sr2 Mg(B03)2 were prepared by high temperature
      solid-state reaction technique. The phase purity was characterized by the powder
      X-ray diffraction (XRD). The luminescence properties in VUV-Vis range as well as
      the decay curves were investigated. The results demonstrate that the band near
      178 nm in the VUTV excitation spectra is ascribed to the host-related absorption.
      The bands of lowest spin-allowed and spin-forbidden f--d transition are located
      at 235 and 278 nm, respectively. The strongest emission is at 543 nm upon 172 nm
      excitation and with the color coordinate (0.30, 0.45). The decay time is about
      2.8 ms.

PMID- 21942016
TI  - [TG-FTIR analysis of thermal degradation of bischofite's crystals with aniline
      hydrochloride].
AB  - The dehydration of bischofite is the key to the use of magnesium resource. Double
      salts or complex method is an important way to prepare anhydrous magnesium
      chloride. The crystals of bischofite and aniline hydrochloride were prepared
      through lowering the temperature of the mixture's aquatic solution slowly. The
      pyrolysis of aniline hydrochloride, bischofite and the crystals was qualitatively
      analyzed by TG-FTIR under 400 degrees C. We infered the reaction process through
      qualitative detection of escaping gas of each decomposition step. The
      Experimental results showed that there were three steps in the thermal
      decomposition of bischofite. In the first step, nearly four crystallized waters
      decomposed, while hydrolysis and decomposition took place together in the next
      two steps, but hydrolysis was the main reaction at the lower temperature (205-235
      degrees C), and comparative decomposition was the main one at the higher
      temperature (235-287 degrees C). In the experimental temperature range, aniline
      hydrochloride didn't decompose. Water and aniline hydrochloride left the crystals
      at different temperature, and no hydrolysis reaction occurred. Anhydrous
      magnesium chloride can be prepared though this way.

PMID- 21942017
TI  - [In situ FTIR and XPS study on selective hydrodesulfurization catalyst of FCC
      gasoline].
AB  - Improvement of the selectivity of hydrodesulfurization (HDS) for hydrogenation
      (HYD) of olefins is crucial to produce sulfur-free (S < 0.001%) gasoline from
      fluid catalytic-cracked (FCC) gasoline. A series of sulfided CoMo/Al2O3 catalysts
      with different metal loading were prepared by pore-filling impregnation. MoS2 and
      COMoS active phases on the surface of sulfided COMo/Al2O3 catalyst were
      identified and analyzed quantitatively by XPS and in-situ FTIR of adsorbed CO.
      The results reveal that the increase in COMoS phase on the catalyst surface
      improves the HDS activity and selectivity. And the HDS selectivity correlates
      linearly with the ratio of active site number of CoMoS and MoS2, the higher the
      ratio of active site number of CoMoS and MoS2, the better the HDS selectivity. In
      situ variable temperature FTIR analysis shows that CoMoS phase has stronger
      electron accepting ability than MoS2. The strong electron deficient property of
      CoMoS active sites is the main reason for its excellent HDS activity and
      selectivity.

PMID- 21942018
TI  - [Genetic programming used for the measurement of CO concentration based on
      nondispersive infrared absorption spectroscopy].
AB  - Nondispersive infrared absorption spectroscopy(NDIR) is an important method to
      measure CO concentration in the air. In the present study, an open-path
      measurement system and continuous measuring device was developed, and genetic
      programming was used to establish the calibration model of subjects' light
      intensity sampling values. Continuous measurements were carried out in 10
      different concentration of CO, and 40 sampled data were acquired and analyzed.
      For validation set, the correlation coefficient was 0.9997. The biggest relative
      error of validation was 4.00%, and the average relative error was 1.11%. Results
      show that genetic programming can be a good method for the modeling of gas
      concentration measurements equipped with NDIR systems.

PMID- 21942019
TI  - [High precision all-reflection Fourier transform imaging spectrometer spectral
      calibration using homogeneous broadening of the wave number model].
AB  - All-reflection Fourier transform imaging spectrometer (ARFTIS) is a novel imaging
      spectrometer. The specialty is not only high spectrum resolution, but also wide
      band and non-chromatism. It is good for remote sensing field of wide band
      imaging. Single spectrum calibration, average calibration and weighted average
      calibration are three common calibration methods. However, they all are limited.
      Because they cannot meet the demand on both convenience and high precision. In
      the present paper, the authors propose a novel model for spectrum calibration. It
      can work in high precision with single spectrum calibration. At the same time,
      the method is steady, and the average error is less than 5% with multi-bands
      calibration. It provides a convenient way for the non-professional calibration
      situation and outer simply calibration work.

PMID- 21942020
TI  - [Using barium fluoride fine particles as stationary phase for TLC/FTIR analysis].
AB  - In situ TLC/FTIR technique has tremendous potential in the analysis of complex
      mixtures. However, the progress in this technique was quite slow. The reason is
      that conventional stationary phase such as silica gel etc. has strong absorption
      in FTIR spectrum and thus brings about severe interference in the detection of
      samples. To solve the problem, the authors propose to use barium fluoride fine
      particles as stationary phase of TLC plate. The reasons are as follows: Barium
      fluoride wafer has been extensively used as infrared window in FTIR experiments
      and it has no absorbance in an IR region between 4 000 and 800 cm'. As a matter
      of fact, the atomic mass of barium and fluoride is quite large, thus the normal
      vibration of BaF2 lattice is limited in far-IR region and low frequency part of
      mid-IR region. Therefore, the interference caused by IR absorption of stationary
      phase can be resolved if BaF2 is used as stationary phase of TLC plate. Moreover,
      BaF2 is quite stable and insolvable in water and most organic solvents and it
      will not be dissolved by mobile phase or react with samples in TLC separation.
      Additionally, decreasing the particle size of BaF2 is very important in TLC/FTIR
      analysis technique. The reason is two-fold: First, decreasing the particle size
      of stationary phase is helpful to improving the efficiency of separation by TLC
      plate; second, decreasing the size of BaFz particle can improve the quality of
      FTIR spectra by alleviating the problem of light scattering. By optimizing the
      synthetic conditions, fine particles of barium fluoride were obtained. SEM
      results indicate that the size of the BaF2 particles is around 500 nm. FTIR
      spectrum of the BaF2 particles shows that no absorption of impurity was observed.
      Moreover, the elevation of baseline caused by light scattering is insignificant.
      The authors have developed a new technique named "settlement volatilization
      method" to prepare TLC plate without polymeric adhesive that may bring about
      significant interference in FTIR analysis. Preliminary TLC experiments proved
      that the TLC plate using BaF2 fine particles as stationary phase can separate
      rhodamine B from methylene blue successfully. Applications of barium fluoride
      fine particles as stationary phase have bright perspective in the development of
      new in-situ TLC/FTIR analysis techniques.

PMID- 21942021
TI  - [Rapid analysis of added ingredients in heroin].
AB  - The method of rapid analysis of added ingredients in heroin was studied in the
      present paper. Adding sucrose, fructose, glucose, starch, caffeine and phenacetin
      to heroin with a certain percentage, the changes in the infrared spectrum with
      the concentration of heroin increasing and the detection limit of the additives
      were determined. Whether or not heroin can be detected in the sample with high
      concentration of added ingredients was studied using Raman spectroscopy.
      Similarly, in high purity of heroin, whether or not Raman spectroscopy can detect
      the added ingredients was tested. Through systematic experiments, the results
      showed that: using infrared spectroscopy and Raman spectroscopy to test the added
      ingredients of heroin is a rapid and effective method. Each has both advantages
      and disadvantages. We should select the appropriate method according to the
      actual cases.

PMID- 21942022
TI  - [Application of DPLS-based LDA in corn qualitative near infrared spectroscopy
      analysis].
AB  - NIR technology is a rapid, nondestructive and user-friendly method ideally suited
      for Qualitative analysis. In this paper the authors present the use of
      discriminant partial least Squares (DPLS)-based linear discriminant analysis
      (LDA) in corn qualitative near infrared spectroscopy analysis. Firstly, a
      training set including 30 corn varieties (each variety has 20 samples) was used
      to build the DPLS regression model, and 28 principal components (DPLS-PCs) were
      obtained from original spectrum. Secondly, the DPLS-PCs scores of the training
      set were extracted as DPLS features. Thirdly, LDA was applied to the DPLS
      features, determining 26 principal components (LDA-PCs). A test sample was first
      projected onto the DPLS-PCs and then onto the LDA-PCs, and finally 26 DPLS+LDA
      features were obtained. The recognition results were obtained by minimum distance
      classifier. DPLS+LDA method achieved 96.18% recognition rate, while traditional
      DPLS regression method and DPLS feature extraction method only achieved 85.38%
      and 95.76% recognition rate respectively. The experiment results indicated that
      DPLS +LDA method is with better generalization ability compared with traditional
      DPLS regression method and NIRS analysis by DPLS+LDA method is an efficient way
      to discriminate corn species.

PMID- 21942023
TI  - [Determination of taste quality of green tea using FT-NIR spectroscopy and
      variable selection methods].
AB  - The present paper was attempted to study the feasibility to determine the taste
      quality of green tea using FT-NIR spectroscopy combined with variable selection
      methods. Chemistry evaluation, as the reference measurement, was used to measure
      the total taste scores of green tea infusion. First, synergy interval PLS (siPLS)
      was implemented to select efficient spectral regions from SNV preprocessed
      spectra; then, optimal variables were selected using genetic algorithm (GA) from
      these selected spectral regions by siPLS, and the optimal model was achieved with
      Rp = 0.8908, RMSEP = 4.66 in the prediction set when 38 variables and 6 PLS
      factors were included. Experimental results showed that the performance of siPLS
      GA model was superior to those of others. This study demonstrated that NIR
      spectra could be used successfully to measure taste quality of green tea and
      siPLS-GA algorithm has superiority to other algorithm in developing NIR spectral
      regression model.

PMID- 21942024
TI  - FTIR analysis of protein secondary structure in cheddar cheese during ripening.
AB  - Proteolysis is one of the most important biochemical reactions during cheese
      ripening. Studies on the secondary structure of proteins during ripening would be
      helpful for characterizing protein changes for assessing cheese quality. Fourier
      transform infrared spectroscopy (FTIR), with self-deconvolution, second
      derivative analysis and band curve-fitting, was used to characterize the
      secondary structure of proteins in Cheddar cheese during ripening. The spectra of
      the amide I region showed great similarity, while the relative contents of the
      secondary structures underwent a series of changes. As ripening progressed, the
      alpha-helix content decreased and the beta-sheet content increased. This
      structural shift was attributed to the strengthening of hydrogen bonds that
      resulted from hydrolysis of caseins. In summary, FTIR could provide the basis for
      rapid characterization of cheese that is undergoing ripening.

PMID- 21942025
TI  - [Raman spectrum study of the calcium phosphate glass structure affected by the
      addition of TiO2].
AB  - Calcium phosphate glasses in which part of CaO was replaced by TiO2 were prepared
      by the conventional melt quench method. The structures and their thermal
      properties were studied by XRD, Raman and DSC techniques. The results show that,
      TiO2 and calcium phosphate form homogeneous glass with the amount of the additive
      less than 3 mol%. The glasses matrix generates a Ca2P2O7 and CaTi4 (PO4)6 crystal
      phase with the amount of the additives in the range of 6-12 mol%. With the
      addition of TiO2, the structural changes of the glass system are from
      metaphosphate to pyrophosphate and orthophosphate. With the TiO2 less than 3
      mol%, the cohesion of the glasses structure and the glasses thermal stability is
      enhanced, and the glasses transition temperature is gradually increased.

PMID- 21942026
TI  - [Raman spectroscopic quantitative analysis of cluster structure of binary alkali
      silicate glasses].
AB  - A calibration method for Raman spectroscopic quantitative analysis of binary
      alkaline silicate glasses is proposed. By applying ab initio quantum chemistry
      simulation, Raman optical activities (ROA) of various cluster units consisting of
      silicon-oxygen tetrahedra (SiOT) with different number of non-bridging oxygen
      (NBO) can be obtained. Thus, experimental results could be calibrated in order to
      reflect and represent directly the true relative density of various silicon
      oxygen tetrahedra existing inside the silicate glasses. Cation effect on the
      intensity of Raman bands was also observed and discussed.

PMID- 21942027
TI  - [XPS and Raman studies of diamond-like carbon films prepared by various
      deposition techniques].
AB  - Diamond-like carbon (DLC) films were deposited on a silicon chip substrate by a
      metal pulsed magnetic filtered cathodic vacuum arc deposition technique, a direct
      current magnetron sputtering technique and a pulsed glow discharge plasma
      enhanced chemical vapor deposition technique. And the characteristics of DLC
      films were investigated using laser Raman spectroscopy and X-ray photoelectron
      spectroscopy. The spectra of diamond like carbon were collected using Raman
      spectrometers with 325 nm flters. It was found that DLC films prepared by various
      deposition technique have different G-peak, D-peak, T-peak, the full width at
      half maximum(FWHM)of G-peak, D-peak and T-peak, the intensity ratio I(D)/I(G) and
      I(T)/I(G) and the sp3 content. Among them, the films grown by metal pulsed
      magnetic filtered cathodic vacuum arc deposition technique have the largest G
      peak wave number and the intensity ratio I(T)/I(G), the minimum of the intensity
      ratio I(D)/I(G), G-FWHM and the maximum sp3 content; those grown by the direct
      current magnetron sputtering technique have the 2nd largest G-peak wave number,
      the intensity ratio I(D)/I(G) and I(T)/I(G) and sp3 content, however, they have
      the largest G-FWHM, while those grown by the pulsed glow discharge plasma
      enhanced chemical vapor deposition technique have the minimum G-peak wave number
      and the intensity ratio I(T)/I(G) and sp3 content, and the maximum intensity
      ratio I(D)/I(G).

PMID- 21942028
TI  - [The study of vibrational spectra of 3-amino-2, 5-dichlorobenzoic acid by density
      functional theory].
AB  - To understand the relationship between the vibrational spectra and the geometry
      structure of 3-amino-2, 5-dichlorobenzoic acid (3A2, 5DBA) essentially, geometry
      optimizations and vibrational frequencies calculation of 3A2, 5DBA were performed
      at Hartree-Fock (HF) and Becke's three-parameter hybrid functional (B3) for the
      exchange part and the Lee-Yang-Parr (LYP) correlation function (B3LYP) level
      using 6-311G(d, p) basis set, respectively. The structural information and 45
      complete normal vibrational modes of 3A2, 5DBA were obtained. Comparing the
      computational geometric parameters of 3A2, 5DBA with the values observed in
      experimental measurement of benzoic acid as well as the computed vibrational
      frequencies of 3A2, 5DBA with the reported data of pertinent literature, it was
      revealed that the results coming from B3LYP/6-311G(d, p) are more reasonable than
      those by HF/6-311G(d, p). Taking into account the difference between the computed
      3A2, 5DBA molecule and the experimental measured sample, the calculated
      vibrational frequencies were reasonably scaled. Under the B3LYP/6-311G(d, p)
      method, the scale factor was 1.0013 for the vibrational frequencies with wave
      numbers <800 cm(-1), while the scale factor was 0.9613 for the vibrational
      frequencies with wave numbers >800 cm(-1). With the help of Gaussian View
      software package, the theoretically calculated vibrational frequencies were
      assigned much more accurately. In addition, the vibrational analysis of
      substitutive groups and main functional groups of 3A2, 5DBA was carried out.
      Through the comparison of the calculated vibrational frequencies with the
      frequencies of 3A2, 5DBA observed in FTIR experiment, the authors found that the
      theoretically calculated vibrational frequencies scaled reasonably were in
      excellent agreement with the data coming from experimental measurements.
      Meanwhile, according to the related literature reports, it was shown that our
      work done in the paper about vibrational assignments and vibrational analysis of
      3A2, 5DBA turned out to be reasonable.

PMID- 21942029
TI  - [Terahertz spectroscopic testing of food additive tert-butylhydroquinone].
AB  - Terahertz time-domain spectroscopy (THz-TDS) technique has a wide range of
      applications in nondestructive testing. After many years study, people have found
      that many materials have characteristic absorptions in terahertz range. This
      letter studies the THz spectra of tert-butylhydroquinone (TBHQ), a food additive
      that was reported excessively in Mak chicken of McDonald. The authors applied
      terahertz nondestructive testing technique in identifying this material, testing
      the absorption and refractive index. The absorption spectra of TBHQ and flour
      mixture in 0.2-2.2 THz were also investigated. The simulation of vibration for
      single molecular was undertaken. The results represent that this method is
      possible by comparing the difference in absorption lines and this method paves
      the way for detecting food additives.

PMID- 21942030
TI  - Absorption line profile recovery based on TDLS and MEMS micro-mirror for
      photoacoustic gas sensing.
AB  - A novel and efficient absorption line recovery technique is presented. A micro
      electromechanical systems (MEMS) mirror driven by an electrothermal actuator is
      used to generate laser intensity modulation through the mirror reflection.
      Tunable diode laser spectroscopy (TDLS) and photoacoustic spectroscopy (PAS) are
      used to recover the target absorption line profile which is compared with the
      theoretical Voigt profile. The target gas is 0.01% acetylene (C2H2) in a nitrogen
      host gas. The laser diode wavelength is swept across the P17 absorption line of
      acetylene at 1535.4 nm by a current ramp, and an erbium-doped fibre amplifier
      (EDFA) is used to enhance the optical intensity and increase the signal-to-noise
      ratio (SNR). A SNR of about 35 is obtained with 100 mW laser power from the EDFA.
      Good agreement is achieved between the experimental results and the theoretical
      simulation for the P17 absorption line profile.

PMID- 21942031
TI  - [Researches on the effect of gas humidity on photoacoustic spectroscopy gas
      detection system].
AB  - Environmental influence is the important factor in a photoacoustic spectroscopy
      gas detection (PASGD) system when it is applied in the industrial field. The
      experiments show that the sensitivity of condenser microphone is affected mostly
      by the humidity of the gas under test, leading to the PASGD's result drift. The
      present paper puts forward a method to eliminate the influence of gas humidity. A
      speaker is fixed in the photoacoustic cell, whose amplitude is regarded as the
      sensitivity self-adaption characterization of sound sensor, used to correct the
      photoacoustic signal amplitude. Thus the problem of sensitivity changing in sound
      detection with condenser microphone is solved. Based on this method, a
      photoacoustic experimental setup, equipped with a diode laser, a resonant
      photoacoustic cell and a lock-in amplifier, was applied to compare the test for
      different humidity samples. The results show that this method is useful to
      eliminating the gas humidity influence and enhancing environmental adaptability
      of PASGD system.

PMID- 21942032
TI  - [Study of three-dimensional fluorescence spectra for measuring chlorobenzene in
      water].
AB  - Quantitative analysis of chlorobenzene (CB) in water by three-dimensional
      fluorescence spectrometry was discussed in the present paper. The study showed
      that there is only one fluorescence peak for CB which lies in the range of
      excitation wavelength (lambdaex) 210-240 nm and emission wavelength (lambdaem)
      330-370 nm. When measuring CB solution of concentration 0.002-0.05 mg x L(-1),
      the fluorescence intensity was the strongest as lamdaex/lamdaem was 225/340 nm,
      which presented linear correlation with concentration, and the related
      coefficient was 0.99967. The study proved that three-dimensional fluorescence
      spectrometry can be adopted for quantitative analysis of CB in water. With this
      method, the detection limit was 3.68 X 10(-6) mg x L(-1) and the standard
      deviation was 0.04% at 90% confidence level.

PMID- 21942033
TI  - [Application of chemometric methods in three-dimensional fluorescence spectral
      analysis].
AB  - With the increasing complexity of analytical data, traditional data processing
      methods for spectral analysis can not meet the analysis needs. The chemometrics
      uses methods of mathematics, statistics and computer sciences to design optimum
      chemical measurement procedures and to provide maximum information about
      fluorescence spectrum by analyzing data. In the present paper, the main kinds of
      three-dimensional fluorescence spectrum, which are widely analyzed by chemometric
      methods, were illustrated at first. Secondly, an overview of the chemometric
      methods such as statistical methods, pattern recognition, neural network and the
      second-order calibration methods is presented. And the applications of these
      methods are followed by. Finally,the prospect of chemometric methods applied in
      multidimensional spectral analysis is discussed.

PMID- 21942034
TI  - [Design and synthesis of imine compound for metal cation logical gates
      recognition and setup of double-control fluorescent molecule switch].
AB  - The Schiff base's reduced product N,N-bis(4-methoxybenzyl) ethane-1,2-diamine,
      which was used as a receptor L, was designed and synthesized for the first time
      in the present article. It was found that Cu2+ and Fe3+ could quench L in
      fluorescence observably and Zn2+ and Cd2+ could enhance L remarkably. So the two
      pair metal cation could set up "OR" logical gate relation with the receptor
      molecule L, then a logical recognition system be formed. The data of resolved
      ZnL's single crystal indicated that ZnL belonged to monoclinic (CCDC No. 747994).
      Integrated spectrum instrument was used to characterize the structure of its
      alike series of complex compound. According to ZnL's excellent fluorescence
      character and the ability to exchange with contiguous metal cation,
      ZnZ+/ZnL/Co2+, Zn2+/ZnL/Nit+ fluorescent molecule switch was designed. It is
      hoped that the work above could be positive for the development of molecule
      computer, bio-intellectualized inspection technology (therapy) and instrument.

PMID- 21942035
TI  - [Studies on the oxidation of tyrosine induced by hydroxyl radical with
      fluorescence spectroscopic method].
AB  - Dityrosine is a marker of tyrosine oxidation. To study effecting factors of
      hydroxyl radical on tyrosine oxidation, synchronous fluorescence spectra with two
      dimensional correlation was used. The results showed that the peak position and
      intensity of dityrosine changed while pH value varied. In the system of tyrosine
      oxidation, with the increment of tyrosine concentration, the concentration of
      dityrosine decreased. With the increment of hydrogen peroxide concentration, the
      concentration of dityrosine increased. The oxidation reaction was prone to taking
      place in acid conditions while difficult to develop in basic conditions. With the
      development of oxidation reaction, the fluorescence intensity of dityrosine
      increased and then decreased. Two dimentional correlation synchronous
      fluorescence spectra showed that the variation in the intensity at 292 nm
      preceded that of 281, 300 and 374 nm. Thus, fluorescence spectroscopy was simple
      and easy for studying tyrosine oxidation induced by hydroxyl radical.

PMID- 21942036
TI  - [New methods and technologies expandable to the laser detection of biological and
      medical samples].
AB  - The multicolour three-photon resonant photoionization spectra and high-time
      resolved laser spectrum of UI were measured with a setup composed of a Nd:YAG
      laser (532 nm, operated at 10 Hz)-pumped pulsed tunable dye laser system, a time
      of-flight mass spectrometer, including micro-channel plate components, ns
      oscilloscope, boxcar integrator, and so on. Creative inventions of this paper are
      for the first time by laser-induced quantum population of the graphic method, the
      causes for single-colour and two-colour three-photon resonant photoionization
      spectra peak were given in the three-colour three-photon resonant photoionization
      experiment; The question how to avoid producing single-colour and two-colour
      three-photon resonant photoionization spectra peak was solved, That is, how to
      solve the problem to avoid "false peaks", so that multicolour three-photon
      resonant photoionization purity was raised remarkably; On this basis, not only in
      close proximity to energy level position with just a difference 0.642 cm, the
      isotopes A and B of uranium, which are difficult to distinguish, were well
      resolved, but the two excited state lifetime values were obtained respectively.
      This technology is not limited to uranium spectrum, but more importantly, it's
      versatile. The new methods and technologies of basic research can be expanded to
      samples of biological and medical research fields with laser detecting and
      analysis.

PMID- 21942037
TI  - [Multi-population elitists shared genetic algorithm for outlier detection of
      spectroscopy analysis].
AB  - The present paper proposed an outlier detection method for spectral analysis
      based on multi-population elitists shared genetic algorithm. The method was
      exploited in the NIR data set analysis to remove the outliers from the data set,
      and partial least squares (PLS) was combined with the proposed method to build a
      prediction model. In contrast with Monte Carlo cross validation, leave-one-out
      cross validation, Mahalanobis-distance and traditional genetic algorithm for
      outlier detection, the prediction residual error sum of squares (PRESS) for
      moisture prediction model based on the proposed method decreases in the rate of
      72.4%, 39.5%, 39.5% and 14.5%; the PRESS value for fat prediction model decreases
      in the rate of 86.2%, 75.9%, 84.9% and 19.9%; and the PRESS value for protein
      prediction model decreases in the rate of 56.5%, 35.7%, 35.7% and 18.2%
      respectively. Results indicated that the method is applicable for spectral
      outlier detection for different species, and the model based on the data set
      without the removed outliers is more accurate and robust.

PMID- 21942038
TI  - [Spectroscopy study on the selectively distinguishing cefalexin with the
      molecular imprinted polymer].
AB  - Molecular imprinted polymers of cefalexin (CFL) were prepared by non-covalent
      molecular imprinting technique in the present paper. Using CFL as template
      molecule, acrylamide (AM) or methacrylic acid (MAA) as functional monomer,
      ethylene dimethacrylate (EGDMA) as cross-linker, AIBN as initiator and methanol
      as porogen agent, different molecularly imprinted polymers (MIPs) of CFL were
      synthesized by bulk or suspension polymerization as synthetic method. The
      intermolecular action between AM and CFL was investigated by UV and IR
      spectrophotometric analysis, and the results indicated that polymerizing
      functional monomer AM could bond effectively with template molecule CFL. By using
      UV spectrophotometric analysis method, it was found that the MIP prepared with AM
      EGDMA by bulk polymerization showed the highest binding capacity for CFL. Test of
      selective adsorption made clear that the MIP represented more excellent
      identification property to CFL than to cefadroxol and ampicillin. The MIPs were
      used as solid-phase extraction sorbent for extraction and enrichment of CFL in
      actual samples. And the recoveries for CFL extraction were found to be 99.3%
      99.7% (n=3), demonstrating the feasibility of the prepared MIPs for CFL
      extraction.

PMID- 21942039
TI  - [Single-trial estimation of dynamic spectrum].
AB  - To improve the efficiency and accuracy of the dynamic spectrum data processing,
      the method of single-trial estimation was adopted. First, the rising edge of the
      whole band PPG was extracted, which was calculated by averaging superimposed
      collected photoelectric plethysmography (PPG) at all wavelengths as a template
      per single pulse; Second, this template was used to correct the rising edge of
      PPG at all wavelengths, and the difference of absorbance was calculate, and then
      a single-trial DS was obtained; finally, the single-trial DS which contained the
      gross error under the 3sigma criterion was removed, and then the remaining
      superimposed single-trial DS was averaged as the final output of the DS. Data
      measured from 10 volunteers were compared with the results of the extraction in
      frequency domain: the correlation coefficient distribution of the DS from the
      same finger of the same individual was improved from 0.006775 to 0.0003840; the
      correlation coefficient distribution of the DS from the different fingers of the
      same individual was improved from 0.01393 to 0.002205, whereas the differences of
      DS between different indivisuals with high quality, and accelerate the process of
      DS put into practical application.

PMID- 21942040
TI  - [Spectra and influences of Rayleigh and stimulated Brillouin scattering in fiber
      optic distributed disturbance sensor].
AB  - Spectra and influences of Rayleigh backscattering (RB) and stimulated Brillouin
      scattering (SBS) in the fiber-optic distributed disturbance sensor (FDDS) were
      investigated. Models of RB, double RB (DRB) and SBS in long fibers were
      established. By numerical simulation, it was found that optical signal-to-noise
      ratio is extraordinarily reduced due to SBS and RB, which results in location
      errors. Numerical results were confirmed by experiments and helpful to improving
      the location precision for applications with long monitored length.

PMID- 21942041
TI  - [Monitoring models of the plant nitrogen content based on cotton canopy
      hyperspectral reflectance].
AB  - Cotton production for accurate non-destructive, rapid monitoring of plant
      nitrogen content there is an urgent demand. Canopy spectral characteristics of
      the cotton plant and its quantitative relationship between nitrogen content, can
      achieve non-destructive monitoring of cotton nitrogen. Two consecutive years by
      different nitrogen test, cotton canopy hyperspectral data collection and
      simultaneous determination of canopy nitrogen content, analysis of different
      fertilizer treatments of cotton canopy spectral characteristics and the
      relationship between nitrogen content of cotton, the results show that: nitrogen
      content of cotton plant in different periods and spectral reflectance in the
      visible band (400-700 nm) was negatively related to the near-infrared 700-1300 nm
      band was a significant positive correlation, and in the short-wave infrared 1300
      1800 nm band correlation is more complicated. Canopy scale, the whole growth
      stage of cotton, the visible band are sensitive to nitrogen content in cotton
      band, and near-infrared only is the cotton boll nitrogen content of the sensitive
      band; short-wave infrared band only in the budding period Cotton nitrogen
      sensitive band. Using nitrogen-sensitive bands in different periods can be
      constructed Cotton Cotton Nitrogen monitoring indicators.

PMID- 21942042
TI  - [Based on Moire interference accurate detection of the laser center wavelength].
AB  - To improve spectrum resolution of the traditional Fourier interferometer with the
      same size lens, was proposed based on orthogonal wedge Fourier interferometer
      system. The interferometer system gets the optical path difference by the prism
      of two mutually perpendicular, which can make the laser Interferences on the CCD
      Array. The detector use the area array CCD linear array CCD, and the system
      collected the interference fringes on the two-dimensional plane. On the basis of
      the spectrum distribution of orthogonal inclination Moire interferometer by
      calculating optical path difference function, the system made the splicing of
      interference fringes on the area array CCD and Moire transform, finally got the
      spectrum resolution. The results from the MATLAB simulation software shows that
      the Maximum optical path difference of the orthogonal inclination Moire
      interferometer can be generated up to 234 microm, which is higher than the
      traditional Fourier interferometer about one order of magnitude, so the spectrum
      resolution also increased by nearly 10 times theoretical. Experimental
      calibration of the spectrometer with a selection of LAB SPAKR 750A-type
      spectrometer, measurements for the center wavelength of 635 nm semiconductor
      laser, the results show basically the same center wavelength position. However,
      the spectrum detected by orthogonal inclination Moire interferometer system near
      the center wavelength is better than the traditional interferometer system.

PMID- 21942043
TI  - [The design and implementation of the web typical surface object spectral
      information system in arid areas based on .NET and SuperMap].
AB  - The characteristic of object spectrum is not only the base of the quantification
      analysis of remote sensing, but also the main content of the basic research of
      remote sensing. The typical surface object spectral database in arid areas oasis
      is of great significance for applied research on remote sensing in soil
      salinization. In the present paper, the authors took the Ugan-Kuqa River Delta
      Oasis as an example, unified .NET and the SuperMap platform with SQL Server
      database stored data, used the B/S pattern and the C# language to design and
      develop the typical surface object spectral information system, and established
      the typical surface object spectral database according to the characteristics of
      arid areas oasis. The system implemented the classified storage and the
      management of typical surface object spectral information and the related
      attribute data of the study areas; this system also implemented visualized two
      way query between the maps and attribute data, the drawings of the surface object
      spectral response curves and the processing of the derivative spectral data and
      its drawings. In addition, the system initially possessed a simple spectral data
      mining and analysis capabilities, and this advantage provided an efficient,
      reliable and convenient data management and application platform for the Ugan
      Kuqa River Delta Oasis's follow-up study in soil salinization. Finally, It's easy
      to maintain, convinient for secondary development and practically operating in
      good condition.

PMID- 21942044
TI  - [Inversion of the lake total nitrogen concentration by multiple regression
      kriging model based on hyperspectral data of HJ-1A].
AB  - The content of total nitrogen in the waters is an important index to measure lake
      water quality, and the technique of remote sensing plays a large role in
      quantitatively monitoring the dynamic change and timely grasping the status of
      lake pollution. Taking Chaohu as an example, quantitative inversion models of
      total nitrogen were established by multivariable regression Kriging under
      analyzing of an correlation between total nitrogen and chlorophyll-a or suspended
      solids by HIS hyperspectral remote sensing data of HJ-1A satellite. The result
      shows that the correlation of 0.76 was discovered between total nitrogen and the
      multiple combination with band 72, band 79 and band 97, while the correlation
      could be increased to 0.83 by applying combined model of multiple linear
      regression and ordinary Kriging. The optimization of the residuals of the
      conventional regression model can improve the accuracy of the inversion
      effectively. These results also provide useful exploration for further
      establishing a common model of quantitative inversion of lake total nitrogen
      concentration.

PMID- 21942045
TI  - [Study on molecular spectrum of fried linseed oil].
AB  - In order to ensure security of fried food and find out regularity of frying oil,
      the change of linseed oil fried in different time was investigated by three
      dimensional fluorescence and UV. The experiment results showed that the property
      of fried oil has not changed obviously in first two hours, but with the
      prolongation of frying time, the fluorescence spectra and UV spectra of fried
      linseed oil changed immensely after frying for six hours, which indicates that
      more harmful substances were produced after linseed oil was fried more than six
      hours.

PMID- 21942046
TI  - [Characteristic wavelengths analysis for remote sensing reflectance on water
      surface in Taihu Lake].
AB  - The research on characteristic wavelengths analysis of reflectance spectrum is a
      very important and basic task for remote sensing of inland-water color. The
      present paper analyzed remote sensing reflectances of 312 samples measured in
      Taihu Lake between 2006 and 2009, and these reflectances were separated into
      three classes by chlorophyll-a concentrations. The reflectance spectra smoothed
      by Savitzky-Golay algorithm were calculated by first- and second-order
      derivatives. Then, zero values were located in the derivatives and counted at all
      wavelengths. Thus the frequency distribution of zeros at each wavelength was got.
      At which wavelength a local maximum of the frequencies appears a characteristic
      wavelength will most likely be there. These characteristic wavelengths are
      corresponding to maximum, minimum, from-concave-to-convex inflection point and
      from-convex-to-concave inflection point of a spectrum curve. At last the paper
      provided the characteristic wavelengths for Taihu Lake water at the spectral
      coverage from 350 to 900 nm, which are 359, 440, 464, 472, 552, 566, 583, 628,
      636, 645, 660, 676, 689, 706, 728, 791, 806, and 825 nm. In addition, these
      wavelengths we found were explained by absorption of phytoplankton pigments and
      components of water in Taihu Lake. Being able to distinguish overlaps between
      peaks and vales at the same wavelength in different measurements, the method to
      analyze characteristic wavelengths is universally applicable to various spectrum
      curves. The characteristic wavelengths chosen by the paper are helpful to
      improving some algorithms of retrieval of water quality parameters.

PMID- 21942047
TI  - [Passive SLF spectrum analysis for tracing the mining dynamic of CBM].
AB  - Exploration and development of the coal-bed methane (CBM) is very important to
      economics, environment and society. It is a key factor to trace and assess the
      process of the coal-bed gas mining dynamically for its efficient development. In
      the present article, based on the theory of natural resources super low frequency
      (SLF) electromagnetic detecting, the method that uses the SLF to trace the coal
      bed gas mining dynamic is introduced. The field tests in 2007 and 2010 in the Qin
      Shui basin, Shanxi province of China indicate that this method is efficient for
      the dynamic of the coal-bed gas mining.

PMID- 21942048
TI  - [Cross comparison of ASTER and Landsat ETM+ multispectral measurements for NDVI
      and SAVI vegetation indices].
AB  - The present paper investigates the quantitative relationship between the NDVI and
      SAVI vegetation indices of Landsat and ASTER sensors based on three tandem image
      pairs. The study examines how well ASTER sensor vegetation observations replicate
      ETM+ vegetation observations, and more importantly, the difference in the
      vegetation observations between the two sensors. The DN values of the three image
      pairs were first converted to at-sensor reflectance to reduce radiometric
      differences between two sensors, images. The NDVI and SAVI vegetation indices of
      the two sensors were then calculated using the converted reflectance. The
      quantitative relationship was revealed through regression analysis on the scatter
      plots of the vegetation index values of the two sensors. The models for the
      conversion between the two sensors, vegetation indices were also obtained from
      the regression. The results show that the difference does exist between the two
      sensors, vegetation indices though they have a very strong positive linear
      relationship. The study found that the red and near infrared measurements differ
      between the two sensors, with ASTER generally producing higher reflectance in the
      red band and lower reflectance in the near infrared band than the ETM+ sensor.
      This results in the ASTER sensor producing lower spectral vegetation index
      measurements, for the same target, than ETM+. The relative spectral response
      function differences in the red and near infrared bands between the two sensors
      are believed to be the main factor contributing to their differences in
      vegetation index measurements, because the red and near infrared relative
      spectral response features of the ASTER sensor overlap the vegetation "red edge"
      spectral region. The obtained conversion models have high accuracy with a RMSE
      less than 0.04 for both sensors' inter-conversion between corresponding
      vegetation indices.

PMID- 21942049
TI  - [Monte-Carlo algorithm for phase function of medium scattering in radiative heat
      transfer].
AB  - Phase function of the compley distributed systems is the significant parameter in
      the field of radiative heat transfer in medium. The Monte-Carlo method has the
      advantages of both numerical algorithm and experiment measurement. Multiple
      scattering phase function of the complex distributed systems based on the Monte
      Carlo method overcomes the former deficiency and expresses the influence of the
      multiple scattering, also, it can calculate phase functions of any controlled
      volume. According to a number of mathematical experiments, the larger the density
      of the medium is the better-proportioned the scattered energy is in the 4 pi
      solid space.

PMID- 21942050
TI  - [Validation and analysis of water column correction algorithm at Sanya Bay].
AB  - Water column correction has been a substantial challenge for remote sensing. In
      order to improve the accuracy of coastal ocean monitoring where optical
      properties are complex, optical property of shallow water at Sanya Bay and the
      suitable water column correction algorithms were studies in the present paper.
      The authors extracted the bottom reflectance without water column effects by
      using a water column correction algorithm which is based on the simulation of the
      underwater light field in idealized water. And we compared the results which were
      calculated by the model and Christian's model respectively. Based on a detailed
      analysis, we concluded that: Because the optical properties of Sanya Bay are
      complex and vary greatly with location, Christian's model lost its advantage in
      the area. Conversely, the bottom reflectance calculating by the algorithm based
      on the simulation of the underwater light field in idealized water agreed well
      with in situ measured bottom reflectance, although the reflectance was lower than
      in situ measured reflectance value between 400 and 500 nm. So, it is reasonable
      to extract bottom information by using the water column correction algorithm in
      local bay area where optical properties are complex.

PMID- 21942051
TI  - [Preparation and structural analysis of diatomite-supported SPFS flocculant].
AB  - In the presetn study, polymerized ferric sulphate (PFS) flocculant was prepared
      and tested. In the preparation of PFS flocculant, industrial by-product ferrous
      sulfate heptahydrate (FeSO4.7H2O) was reused as the main material. By composition
      with diatomite and drying up at certain temperature in vacuum drying oven, solid
      PFS flocculant was produced. Structural characteristics of the new flocculant
      product were examined through infrared spectroscopy and scanning electron
      microscopy (SEM), which showed that by compositing with diatomite, new group
      bridging emerged in the structure of PFS, which made the bond of groups stronger.
      In addition, part of the metalic contents in diatomite was polymerized with PFS,
      the product of which was polymerized ferric complex. Furthermore, the absorbing
      and agglomerating capacity of the diatomite carrier was significant. Considering
      the factors listed above, the new solid polymerized ferric sulphate (SPFS)
      flocculant was characterized with a larger molecule structure and enhanced
      absorbing, bridging and rolling sweep capacities. Through orthogonal experiment,
      optimum conditions of synthesis were as follows: the ratio of
      FeSO4.7H2O/diatomite in weight was 43/1, the reaction time is 1 h and the
      reaction temperature is 55 degrees C. By wastewater treatment experiment, it was
      found that the synthetic products showed good flocculation performance in the
      treatment of domestic sewage, the removal of COD was 80.00% and the removal of
      turbidity was 99.98%.

PMID- 21942052
TI  - [Study on chemical compositions and crystallinity changes of bamboo treated with
      gamma rays].
AB  - The structures and qualities of main chemical compositions in cell wall of bamboo
      treated with gamma rays were tested by nuclear magnetic resonance spectrometer
      (NMR) and X-ray Diffraction (XRD). The result indicated that the bamboo
      crystallinity increased at the beginning of irradiation process, while the
      crystallinity reduced when the irradiation dose was raised to about 100 kGy.
      During the whole irradiation process, hemicellulose degraded, and with the
      irradiation doses increased the non-phenolic lignin changed to the phenolic.

PMID- 21942053
TI  - [Study on spatial interpolation of the average temperature in the Yili River
      Valley based on DEM].
AB  - On the basis of the monthly mean temperature data of 19 meteorological stations
      from 1961 to 2008 in the Yili River Valley, the correlation between mean annual
      temperature and elevation was analyzed to get access to the temperature lapse
      rate of 0.564 degrees C/100 m. The main purpose of this study was to apply a
      spatial interpolation method based on DEM and compare with the traditional ones
      of inverse distance weight (IDW) and Kriging methods. According to the cross
      validation results, it was concluded that the accuracy of interpolation method
      based on DEM was superior to the other two methods. Combined with DEM data, the
      mean annual temperature distribution map with 90 m resolution was established and
      it expressed the main trend of temperature changing with terrain and reflected
      the spatial variability of temperature.

PMID- 21942054
TI  - [Determination of soil available nutrient contents using multi-element hollow
      cathode lamp].
AB  - The soil available nutrient determination based on atomic absorption spectrometry
      using multi-element hollow cathode lamp (HCL) is improved from the instrument
      using single-element HCLs via modifying the software and hardware. As a test,
      available Cu, Fe, Zn, Mg and Ca contents of 30 fluvo-aquic soil samples measured
      by atomic absorption spectrometry using a multi-element HCL were compared with
      that measured by using single-element HCLs for 3 replications. A significant
      linear relationship with the slope close to 1 was found in soil available Cu, Fe,
      Zn and Ca contents measured by using multi-element HCL and single-element HCLs.
      The linear correlation coefficient of 0.86 and the slope of 0.85 were found in
      soil available Mg content. No significant difference was revealed from the above
      comparison data via analysis of variance. Therefore, the soil available nutrient
      determination based on atomic absorption spectrometry using multi-element HCL has
      the same measurement accuracy and is 50%-60% time-saving compared to that by
      using single-element HCLs.

PMID- 21942055
TI  - [Application of ICP-MS/ICP-AES to detecting nutrition and heavy metal contents in
      grain of detached wheat spikes in vitro culture].
AB  - The heavy metals in the environment led to the defect of nutrient contents in
      grains and metabolic disturbance seriously. In order to research the effect of
      heavy metal copper and cadmium on nutrient contents and heavy metal contents of
      wheat grain, the present paper studied the nutrition element (P, K, Ca, Mg, Na,
      Fe, Mn, Zn and B) and contents of heavy metal (Pb, Cr, Hg, Cu and Cd) in organs
      of detached wheat spikes in vitro culture by ICP-MS/ICP-AES. The results showed
      that the weight of grain reduced significantly with copper and cadmium treatment.
      Under different copper treatment, the contents of P, K, Mg, Ca, Na, Mn and Zn
      increased, but Fe and B contents reduced. Exogenous cadmium promoted the
      absorption of P, K, Ca, Mg and Mn while interrupted the absorption of Na, Fe, Zn
      and B. Exogenous copper and cadmium treatment reduced the Hg content in wheat
      grain, but the Cu and Cd contents were 55-folds and 62 folds of the national food
      sanitation standard. All the data showed that the effects of copper and cadmium
      are disadvantageous to the accumulation of nutrient and heavy metal contents.

PMID- 21942056
TI  - [Determination and correlation analysis of trace elements in Boletus tomentipes].
AB  - The contents of eleven trace elements in Boletus tomentipes were determined by
      inductively coupled plasma atomic emission spectroscopy (ICP-AES). The results
      showed that the fruiting bodies of B. tomentipes were very rich in Mg and Fe
      (>100 mg x kg(-1)) and rich in Mn, Zn and Cu (>10 mg x kg(-1)). Cr, Pb, Ni, Cd,
      and As were relatively minor contents (0.1-10.0 mg x kg(-1)) of this species,
      while Hg occurred at the smallest content (< 0.1 mg x kg(-1)). Among the
      determined 11 trace elements, Zn-Cu had significantly positive correlation (r =
      0.659, P < 0.05), whereas, Hg-As, Ni-Fe, and Zn-Mg had significantly negative
      correlation (r = -0.672, -0.610, -0.617, P < 0.05). This paper presented the
      trace elements properties of B. tomentipes, and is expected to be useful for
      exploitation and quality evaluation of this species.

PMID- 21942057
TI  - [Determination of trace elements Be, Cd, as and Pb in air of residential areas by
      inductively coupled plasma-mass spectrometry coupled with ultrasonic leaching].
AB  - In the present paper, the method for determining the trace elements Be, Cd, As
      and Pb in air of residential areas by inductively coupled plasma-mass
      spectrometry was established. Ultrasonic leaching procedures were applied to
      extract the trace elements from the filter membrane of the atmospheric
      particulates. The operating condition of the instrument was optimized. 72Ge, 115s
      In and 204Tl were chosen as the internal elements and the effect of matrix,
      interface and fluctuation of instrument was overcome effectively. Satisfactory
      linearity of working curves of four elements was obtained, giving all the
      correlation coefficients over 0.9995, and the detection limit of the method was
      between 0.006 and 0.045 ng x m(-3). The mean values of National Standard
      Reference Material GBW(E)080212 were in agreement with the certified values. The
      sampling filters membranes, divided into four equal parts and with added standard
      solution with different concentions were analyzed, and the recovery rate of
      samples were in the range of 91.6%-109.7% with the related standard deviation
      between 0.7% and 4.8%. The obtained results showed that the method of determining
      the trace elements Be, Cd, As and Pb in air of residential areas by inductively
      coupled plasma-mass spectrometry proved to be simple, accurate, sophisticated and
      stable.

PMID- 21942058
TI  - [Determination of trace silver in water samples by solid phase extraction
      portable tungsten-coil electrothermal atomic absorption spectrometry].
AB  - A simple method has been developed for the determination of silver in
      environmental water samples using solid phase extraction with tungsten-coil
      electrothermal atomic absorption spectrometry. Silica gel was used as an
      adsorbent and packed into a syringe barrel for solid phase extraction of silver
      prior to its determination by using a portable tungsten-coil electrothermal
      atomic absorption spectrometer. Optimum conditions for adsorption and desorption
      of silver ion, as well as interferences from co-existing ions, were investigated.
      A sample pH value of 6.0, a sample loading flow rate of 4.0 mL x min(-1), and the
      mixture of 4% (m/v) thiourea and 2% (phi) nitrate acid with the eluent flow rate
      of 0.5 mL x min(-1) for desorption were selected for further studies. Under
      optimal conditions, a linear range of 0.20-4.00 ng x mL(-1), a limit of detection
      (3sigma) of 0.03 ng x mL(-1) and a preconcentration factor of 94 were achieved.
      The proposed method was validated by testing three environmental water samples
      with satisfactory results.

PMID- 21942059
TI  - [Determination of total mercury and ionic mercury in artificial gastric juice of
      Tibetan medicine Dangzuo by GAE-AFS].
AB  - The mercury in Tibetan medicine has become important focus in the research on
      medicine safety evaluation. The total mercury and the ionic mercury in artificial
      gastric juice of Tibetan medicine Dangzuo were detected by Gold Amalgam
      Enrichment-Atomic Fluorescence Spectrometry (GAE-AFS). In the present study,
      Tibetan medicine Dangzuo was prepared by H2SO4-KNO3 digestion system and
      artificial gastric juice. The established method and condition of instrument were
      investigated. Under the optimum experimental conditions and instrumental
      operation parameters, the recovery (n=6) of HgS is 99.56$ (RSD = 1.94%), the
      limit of detection for mercury is 0.2 ng x L(-1), the linear range is 0-500 ng x
      L(-1), and r = 0.9999. Then, the total mercury and the ionic mercury in
      artificial gastric juice in Dangzuo samples from different Tibetan regions were
      assayed. The result showed that the ranges of total mercury and ionic mercury in
      artificial gastric juice were 3.9980-16.7358 x mg x g(-1) and 45.5377-1033.9850
      ng x g(-1), respectively. The analytical method mentioned above is rapid and
      accurate for determining the amount of mercury in Tibetan medicine Dangzuo.

PMID- 21942060
TI  - [Influence of ancient glass samples surface conditions on chemical composition
      analysis using portable XRF].
AB  - Portable X-ray fluorescence analysis (PXRF) is one kind of surface analysis
      techniques, and the sample surface condition is an important factor that
      influences the quantitative analysis results. The ancient glass samples studied
      in the present paper were excavated from Xinjiang, Guangxi, Jiangsu provinces,
      and they belong to Na2O-CaO-SiO2, K2O-SiO2, and PbO-BaO-SiO2 system,
      respectively. Quantitative analysis results of weathered surface and inside of
      the ancient glass samples were compared. The concentration change of main fluxes
      in different parts of the samples was pointed out. Meanwhile, the authors studied
      the effect of distance between the sample and the reference plane, and curve
      shape of the sample on the quantitative results. The results obtained were
      calibrated by three methods, and the validity of these three methods was proved.
      Finally, the normalizing method was proved to be a better method for quantitative
      analysis of antiques. This paper also has guiding significance for chemical
      composition analysis of ancient jade samples using PXRF.

PMID- 21942061
TI  - [Nondestructive analysis of some ancient glass in Jin and Yuan dynasty, by EDXRF
      probe].
AB  - The chemical composition of some glass samples in Jin and Yuan Dynasty were
      analyzed by EDXRF, to discuss the technological character of these glass samples.
      The result shows that the chemical composition of these glass samples is very
      complex. According to the chemical composition, these glass samples include K2-O
      CaO-SiO2, Na2O-CaO-SiO2 and K2O-CaO-PbO-SiO2 glass, and a crystal SiO2 sample
      which was once considered a glass sample. The reason for the color of all blue
      glass samples is the existence of CuO, but not CoO.

PMID- 21942062
TI  - [Preparation of electrodeposited Cr-La coating and its spectral properties].
AB  - Cr-La coating (dc) and Cr-La coating (pulse) were prepared by electrodeposition
      method of direct current and pulsating current respectively. The Cr-La coating
      (dc) and Cr-La coating (pulse) were characterized with ICP-AES, EDAX, XRD and SEM
      techniques, respectively. Cr-La coating(dc) was amorphous. There were crystalline
      La and CrC in Cr-La coating (pulse). The microhardness of the Cr-La coating(dc)
      and Cr-La coating (pulse) were as high as 860.3 and 930.2 HV respectively, which
      were higher 11.15% and 20.18% higher than that of the Cr coating (774.0 HV). The
      wear weight losses of Cr-La coating(dc) and Cr-La coating(pulse) were 1.29 and
      2.25 times lower than that of Cr coating, respectively. The friction coefficient
      of Cr coating, Cr-La coating(dc) and Cr-La coating(pulse) were 0. 884, 0. 640 and
      0. 648 respectively. The properties of wear weight loss and microhardness of
      coatings were improved with pulsating current. The wear weight loss and
      microhardness of Cr-La coating(pulse) were lower 1.75 time lower and higher 8.13%
      higher than that of the Cr-La coating(dc), respectively.

PMID- 21942063
TI  - [Advance in imaging spectropolarimeter].
AB  - Imaging spectropolarimeter (ISP) is a type of novel photoelectric sensor which
      integrated the functions of imaging, spectrometry and polarimetry. In the present
      paper, the concept of the ISP is introduced, and the advances in ISP at home and
      abroad in recent years is reviewed. The principles of ISPs based on novel
      devices, such as acousto-optic tunable filter (AOTF) and liquid crystal tunable
      filter (LCTF), are illustrated. In addition, the principles of ISPs developed by
      adding polarized components to the dispersing-type imaging spectrometer,
      spatially modulated Fourier transform imaging spectrometer, and computer
      tomography imaging spectrometer are introduced. Moreover, the trends of ISP are
      discussed too.

PMID- 21942064
TI  - [Micro Hadamard transform near-infrared spectrometer].
AB  - A new type micro Hadamard transform (HT) near-infrared (NIR) spectrometer is
      proposed in the present paper. It has a MOEMS (Micro-Opto-Electro-Mechanical
      Systems) blazed grating HT mask. It has merits of compactness, agility of dynamic
      mask generation and high scan speed. The structure and theory of this
      spectrometer are analyzed. The 63-order Hadamard-S matrix and mask are designed.
      The mask is dynamically generated by program of MOEMS blazed gratings. The
      spectrum is in agreement with that measured by Shimadzu spectrometer in
      experiments. It has a wavelength range between 900 and 1 700 nm, spectral
      resolution of 19 nm, single scan time of 2.4 s, SNR of 44.67:1, optical path of
      70 mm x 130 mm, and weight under 1 kg. It can meet the requirement of real time
      detection and portable application.

PMID- 21942065
TI  - [Study and simulation of the intensity modulation-Fourier transform
      spectropolarimeter].
AB  - Intensity modulation-Fourier transform spectropolarimetry (IMFTSP) is a novel
      technology that combines the intensity modulation spectropolarimetry and Fourier
      transform spectroscopy. The IMFTSP can obtain full Stokes spectropolarimetric
      parameters simultaneously, and maintains the throughput (Jacquinot) and multiplex
      (Fellgett) advantages. Yet aside from this, the IMFTSP has the advantage of
      reducing the complexity of data processing. The data collecting and
      spectropolarimetric parameters reconstruction processes were analyzed
      theoretically in this paper, the theoretical formulas are presented, and a whole
      process mathematical simulation for the IMFTSP system is introduced. The theory
      analysis and simulation results proved the feasibility of the IMFTSP.

PMID- 21942066
TI  - [Research on photometric calibration and reflectance calculation of CE-1 IIS
      data].
AB  - The interference imaging spectrometer (IIS) is an important payload of the
      Chang'e-1 (CE-1) lunar satellite to achieve the distribution and content analysis
      of major elements and mineral types on the lunar surface. Due to the different
      observing conditions, the obtained lunar brightness varied significantly from
      place to place. Thus, photometric calibration is required to eliminate the
      radiance difference caused by the different observing conditions. In the present
      paper, based on the analysis of IIS-2B data (after radiance calibration) of CE-1
      satellite, we introduced the improved Lommel-Seeliger model to calibrate the IIS
      2B radiance data pixel by pixel. Subsequently, an area adjacent to Apollo16 site
      was selected as the calibration target, and the bidirectional spectrum for soil
      sample 62231 was used as a calibration standard to obtain the reflectance from
      radiance data. Finally, soil sample 71501 was selected to take the accuracy
      evaluation on the reflectance results. Our work is useful for mineral
      identification and information extraction, as well as for the mapping of
      different minerals and rocks distribution on lunar surface.

PMID- 21942067
TI  - [Design and analysis of a depolarizer for the space-borne grating imaging
      spectrometer].
AB  - The main portion of the space-borne grating imaging spectrometer-grating has
      intense polarization response. The objective of spectrometer is to measure the
      intensity accurately without bias as to the incident polarization state. One
      common method to overcome polarization bias in optical systems is the insertion
      of a depolarizer. The theory of horizontal-vertical (H-V) quartz depolarizer
      operation is described. A single H-V depolarizer was met the spectrometer
      polarization requirement according to its polarization character. Both the degree
      of depolarization and image degradation (especially the image doubling) were
      analyzed for the depolarizer design. The analysis results show that it satisfies
      the design requirements of the spectrometer, the polarization sensitivity is
      within the specification of 1% and the decrease in MTF due to the depolarizer is
      less than 1.5%.

PMID- 21942068
TI  - [Research on endmember extraction algorithm based on spectral classification].
AB  - Spectral unmixing is an important task for data processing of hyperspectral
      remote sensing, which is comprised of extracting the pure spectra (endmember) and
      calculating the abundance value of pure spectra. The most efficient endmember
      extracting algorithms (EEAs) is designed based on convexity geometry such as pure
      pixel index (PPI), N-finder algorithm (N-FINDR). Most EEAs choose pure spectra
      from all pixels of an image so that they have disadvantages like slow processing
      speed and poor precision. Partial algorithms need reducing the spectral
      dimension, which results in the difficulty in small target identification. This
      paper proposed an algorithm that classifies the hyperspetral image into some
      classes with homogeneous spectra and considers the mean spectra of a class as
      standard spectra for the class, then extracts pure spectrum from all standard
      spectra of classes. It reduces computation and the effect of system error,
      enhancing the speed and precision of endmember extraction. Using the least
      squares with constraints on spectral extraction and spectral unmixing, by
      controlling the band average value of the maximum spectral redundant allowance to
      control the number of endmembers, does not need to reduce the spectral dimension
      and predetermine the number of endmembers, so compared to N-finder algorithm,
      such algorithm is more rational.

PMID- 21942069
TI  - [The characteristics of multicolor imaging system for logarithmic wavefront
      coding].
AB  - The wavefront coding extension the depth of field (DOE) of an imaging system is
      by insert a phase plate into the pupil plane of a spatially incoherent imaging
      system, the encoded image can be digitally restored to produce a final image with
      improved depth dependent detail. To study the multicolor imaging performance of a
      logarithmic wavefront coding system, the phase and chromatic aberration variation
      with wavelength are analyzed, and characteristics such as shape, distribution and
      width of two wavelengths' PSF are compared. The research results show that if the
      chromatic aberration is excellently corrected then the technology can be used for
      multicolor even broadband spectrum DOE imaging system. Otherwise, the encode
      image can not be effectively decoded.

PMID- 21942070
TI  - [Extracting buildings height and distribution information in Tianjin City from
      the shadows in ALOS images].
AB  - Spectral difference is an important aspect for extracting shadows of buildings.
      Based on the analysis of the relationship between the building heights and the
      shadows in ALOS Images, the paper presents the principle and the method for
      building heights estimation in a city from the shadows of an image, and works out
      a feasible approach to determining shadow zones in a panchromatic ALOS Images. It
      has also contributed a standard process for extracting buildings distribution
      information of different heights in a city from the shadows in a panchromatic
      ALOS Images. A result with about 87.6% accuracy has been achieved while applying
      this technique to Tianjin City, which has demonstrated prospective applications
      of satellite remote sensing to urban purposes.

PMID- 21942071
TI  - [A dual-wavelength spectroscopic method for the low chemical oxygen demand
      determination].
AB  - The present paper reports a dual wavelength spectroscopic method for the
      determination of chemical oxygen demand (COD) of low content samples, based on
      the absorption measurement at 440 and 560 nm. Since the absorptivities of Cr3+ at
      these two wavelengths are the same, a net absorption from dichromate ions can be
      determined by subtracting the absorption at 560 nm (only contributed by Cr3+)
      from the absorption at 440 nm The results showed that the detection limit of
      quantification is 8.6 mg x L(-1) and the relative standard deviations are in the
      2%-15% range for the low COD standard samples (< or = 100 mg x L(-1)) in this
      proposed method. Further more, the method does not require calibration based on
      the standard samples. The present method is simple, reliable, and accurate; it is
      suitable for the application in a mass testing for low COD samples.

PMID- 21942072
TI  - [Simulated annealing based phase correction of interferogram in Fourier transform
      imaging spectrometer].
AB  - Phase correction is one of the key technologies in the spectrum recovery of the
      Fourier transform imaging spectrometer. The present paper proposes a correction
      method based on simulated annealing algorithm to calculate phase error, which
      overcomes the disadvantage of the existing methods that can not correct the
      interferogram with noise. The method determines the phase optimum solution by
      controlling the phase decrease function, attaining objective function value by
      correcting interferogram data with random phase value generated in the phase
      range, and determining the objective function increment in accordance with the
      Metropolis criterion. The simulation result of the algorithm indicates that the
      optimized phase error is less than 0.5%, and both the error accuracy and
      stability of the spectrum-recovered relative spectrum is less than 1%, which is a
      great improvement compared with the existing algorithm.

PMID- 21942073
TI  - [Image of the month. Thoracic variant of the Chance fracture].

PMID- 21942074
TI  - [Clinical case of the month. Purulent pericarditis in a patient with pulmonary
      sarcoidosis].
AB  - We report the case of a patient, suffering from pulmonary sarcoidosis, who
      developed a purulent pericarditis complicated with a cardiac tamponade. The
      widespread use of antibiotics has progressively reduced the number of purulent
      pericarditis. However, it remains a serious disease that has to be rapidly
      diagnosed to be treated timely. We will review the required tests for the
      diagnosis and the treatment of this pathology that leads to death otherwise. The
      link with pulmonary sardoidosis is uncertain.

PMID- 21942075
TI  - [Patient-physician electronic communication].
AB  - There is a patient demand for online services provided by their doctor, but at
      the present, in Belgium, there are very few physicians offering such services.
      This article examines the different types of services and the practical,
      technical, legal and economic aspects of an interface for electronic doctor
      patient communication in the ambulatory sector in the Belgian context. The
      inventory of pilot projects carried out in other countries shows high patient
      satisfaction rates and a low impact on doctors' workload. However, the lack of
      funding hinders the implementation. Given the confidential nature of data
      exchanged, both high level of security and development of guidelines adapted to
      the local Belgian context are required. Electronic communication should remain
      one of the modalities in a therapeutic relationship. At a technical level, using
      the Belgian electronic identity card and the opportunity to create a digital
      signature with legal value would provide a solution to most of the security
      requirements.

PMID- 21942076
TI  - [In a medical setting, why and how can the doctor identify the patient as a
      victim of abuse].
AB  - People who were victims of childhood abuse (sexual, emotional or physical), later
      on will develop psychosomatic illnesses and psychological problems. These health
      problems, sad consequences of past abuse, will bring them to consult a physician
      at one point or another. But, because these patients often do not talk about the
      ancient trauma, the physician is unaware of this past abuse and only treats the
      illness' symptoms. Abused people will also develop behavioral problems which put
      them repeatedly back into the position of victim, without realizing why. If this
      dysfunctional behavior is not identified as the result of trauma, these multi
      abused patients will go from bad to worse, repeating in an endless cycle their
      role as victim. If the physician is able to identify this typical replay of
      victimization, the patient can be helped to become aware of and to avoid
      compulsive self-abusive behaviors which are discussed in the following article.

PMID- 21942077
TI  - [Skin reactions to tattoo ink].
AB  - Ritual and artistic tattoos rely on the use of numerous pigments which are not
      all entirely inert once placed in the dermis. The compositions of some tattoo
      inks are identified. However, new but less well identified compounds appear on
      the market. Allergic reactions can be present under different aspects. They may
      correspond to allergic contact dermatitis or to photodermatitis. Other reactions
      include allergic hypersensitivity reactions as well as lichenoid, granulomatous
      or pseudolymphoma reactions. Pulsed light and laser are typically used for
      regular tattoo removal. These procedures are not indicated in inflamed tattoos.
      Indeed, the pigment dispersed during photolysis may perpetuate the reaction.
      Pseudotattoos due to the stratum corneum staining are frequently responsible for
      photoeczema.

PMID- 21942078
TI  - [Lung transplantation benefits for terminal lung diseases].
AB  - Lung transplantation is an established treatment of pulmonary diseases at an
      advanced stage. The purpose of our study is to present the benefits, indications
      and complications of this surgical procedure in the CHU of Liege. The cohort
      includes 14 patients transplanted between 2005 and 2009, and who were inserted in
      a pulmonary rehabilitation programme at the university hospital of Liege. The
      criteria of assessment are the values of respiratory function tests at rest and
      exercise, and quality of life. Inherent complications related to this type of
      surgical operation have been collected. We found a dramatic improvement in
      pulmonary function tests performed at rest both immediately after the
      transplantation and after 6 months. Likewise exercise capacity was already
      increased shortly after the transplantation and further improved 6 months later.
      As for health related quality of life, parameters that improved the most were
      dyspnoea and global quality of life, and the improvement was already maximal
      immediately after the transplantation. Our retrospective study confirms the data
      of the literature, namely an improvement of respiratory function, effort capacity
      and quality of life after lung transplantation.

PMID- 21942079
TI  - [Glycemic control before and after sitagliptin in general medical practice:
      analysis of determinant factors in the Belgian observational study "SUGAR"].
AB  - Sitagliptin (Januvia), the first selective inhibitor of dipeptidylpeptidase-4
      with a so-called incretin effect, has been evaluated in SUGAR, a large Belgian
      prospective observational study carried out in general practice. Sitagliptin, at
      a dose of 100 mg once daily, was added to previous treatment of not well
      controlled type 2 diabetic patients (> 95% on metformin monotherapy). Among 605
      patients analysed in intention to treat, the worse the glycaemic control at
      entry, the greatest the reduction in glycated haemoglobin (HbA1c) and fasting
      plasma glucose levels after the addition of sitagliptin (p < 0.001). No specific
      factor was associated with the quality of initial glucose control among age, body
      mass index, the duration of diabetes or the modalities of its pharmacological
      treatment. Similarly, among these factors, none was significantly associated with
      the reduction in HbA1c or fasting plasma glucose levels observed with the
      addition of sitagliptin. Thus, sitagliptin was as active in older as in younger
      subjects, in obese as in nonobese people and in patients with diabetes of long
      versus short duration. In particular, SUGAR recruited data on 191 patients above
      70 years in whom sitagliptin was as effective and safe as in younger patients
      with type 2 diabetes.

PMID- 21942080
TI  - [How I explore...a patient with chronic heart failure].
AB  - Heart failure is defined by precise criteria associating clinical signs and
      cardiac abnormalities. The exploration for signs and symptoms must be associated
      with the systematic realization of an electrocardiogram, a chest X-ray and an
      echocardiogram to rapidly obtain the diagnosis and direct the patient to an
      adapted complementary clarification. Other additional tests are available
      (catheterization, nuclear cardiology imaging,...). The purpose is to confirm the
      diagnosis, to determine the aetiology and to identify factors of poor prognosis.

PMID- 21942081
TI  - [Trabectedin (ET-743/Yondelis) for treating soft tissue sarcomas and ovarian
      cancer].
AB  - Soft tissue sarcomas account for 1% of all malignant tumours. Until a few years
      ago, doxorubicine and ifosfamide were the only active chemotherapy drugs in the
      metastatic setting. Recently, a new drug has proven its efficacy after failure of
      standard treatments: the trabectedin; its activity is based on interference with
      ADN repair mechanisms. Trabectedin has just been also validated and reimbursed in
      patients with ovarian cancer, in partially sensitive recurrence. In this paper,
      we will review the mechanism of action and the clinical results of trabectedin.

PMID- 21942082
TI  - [Diagnosis of non intentional weight loss in adults].
AB  - Significant non intentional weight loss in adults is a problem encountered
      frequently in clinical practice that poses a diagnostic challenge for the
      clinician. Causes are quite diverse, as are the prognostic implications. Cancer,
      gastrointestinal disease, and psychiatric problems were the three most common
      diagnoses, but a significant proportion of patients had no clear cause of their
      weight loss. The prognosis of this subset is generally favourable. Ruling out
      malignancy is one of the prime tasks. The investigation is based on a rational
      stepwise approach with a detailed history, a meticulous physical examination and
      a simple, non-invasive screening battery of tests (laboratory tests and medical
      imaging). A completely normal laboratory screening argues against severe organic
      disease in general and malignancy in particular. Additional testing should be
      targeted towards areas of concern raised by the initial evaluation. If this
      baseline examination is normal and reassuring, a strategy of careful clinical
      follow-up is preferred to non-targeted additional more invasive or expensive
      investigations.

PMID- 21942083
TI  - [Role of fibrinogen Bbeta-chain D-region 454-458 residues for assembly and
      secretion of intact fibrinogen].
AB  - BACKGROUND: To examine the role of fibrinogen Bbeta-chain D region in the
      assembly and/or secretion of multichain protein, we synthesized eight variant
      fibrinogens with truncated Bbeta-chains in the C terminal region, terminating
      with 454, 455, 456 or 458 residues, and with substitution at Bbeta-455Arg by Lys,
      Ile, Ala or Asp in Chinese hamster ovary (CHO) cells. METHODS: A fibrinogen Bbeta
      chain expression vector was altered and transfected into CHO cells that expressed
      normal human fibrinogen Aalpha- and gamma-chains. Expressed fibrinogens of cell
      lysates and culture media of the established cell lines were subjected to ELISA
      and immunoblot analysis. RESULTS: The CHO cells synthesized eight variant Bbeta
      chains and assembled these into fibrinogen except for Bbeta-454 and Bbeta-455Asp.
      However, in the cell lysates, concentrations of these variant fibrinogens were
      lower than that in wild type cells. These assembled variant fibrinogens were
      secreted into the culture medium, and the levels in culture media were also lower
      than that in the medium of wild type cells. Significant differences in the mean
      ratios of fibrinogen concentration in medium to that in cell lysate were not
      observed between the variant type cells and the wild type cells. CONCLUSIONS:
      Residues of the Bbeta-chain D domain are essential for fibrinogen assembly,
      especially the Bbeta-455 residue was critical. The present study indicated that
      the structure of the fibrinogen Bbeta-chain C terminal D region is necessary for
      fibrinogen assembly, but not for secretion.

PMID- 21942084
TI  - [Analysis of brain activity during delayed matching-to-sample test].
AB  - Despite recent advances in uncovering the neural signature of memory processing
      in humans, spatiotemporal characteristics of cerebral activity during mental
      transformation of the visual (color) memory to the visuo-spatial memory has not
      been studied. The aim of this study was to investigate the electrophysiological
      correlates of internal memory transformation based on the event-related potential
      analysis using a root mean square (RMS) and a standardized low resolution
      electromagnetic tomography (sLORETA). Eleven healthy human subjects completed a
      modified delayed matching-to-sample test in which the visual(color) short-term
      memory had to be transformed into the visuo-spatial memory according to the
      matching probe. In comparison with a non-memory control condition, identifiable
      RMS peak was observed 352ms after the matching probe presentation in the
      condition of memory transformation. In this time, sLORETA demonstrated the higher
      current density in the prefrontal region. Our results suggested that the
      prefrontal region is associated with the internal memory transformation process
      depicting a spatiotemporal profile similar to P3b.

PMID- 21942085
TI  - [Tm analysis method using a quenching probe is a simple and rapid way to
      simultaneously detect KRAS and BRAF mutations].
AB  - Epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase
      receptor that, on ligand binding, triggers the RAS-RAF-MAPK signaling pathway
      which is mainly associated with cell proliferation. Drugs targeting EGFR have
      recently entered clinical practice and have proven to be effective in providing
      clinical benefits. However, the presence of mutated KRAS alleles in cancer is a
      predictive marker of anti-EGFR drug resistance. Similarly, alterations of other
      members of the RAS-RAF-MAPK signaling pathway may also be such predictive
      markers, especially the BRAF mutation in colorectal cancer. Therefore, the
      identification of KRAS and BRAF mutations may be important in predicting
      resistance to EGFR-targeted therapies. We looked at the Tm analysis for
      simultaneous detection of KRAS and BRAF mutations using a quenching probe. The
      oligonucleotide probes modified with certain fluorescent dyes at 5'-end cytosine
      are quenched by their interaction with a uniquely positioned guanine. When the
      probe is hybridized with target DNA, its fluorescence is quenched by the guanine
      in the target DNA. However, as the temperature is raised, perfect match probes
      and miss match probes dissociate at different temperatures. Dissociated probes
      generate fluorescence. This simple and rapid method for simultaneous detection of
      these mutations is useful in clinical practice.

PMID- 21942087
TI  - [Relationships among frequency domain and non-linear parameters from heart rate
      variability].
AB  - Frequency domain analysis of heart rate variability (HRV) is used for the
      evaluation of autonomic activity. Non-linear domain parameters from HRV are also
      considered useful. However, properties of the latter have not yet been clearly
      characterized. Therefore, we studied the relationships among the frequency domain
      and non-linear parameters from HRV. Continuous Holter electrocardiographic
      monitoring was conducted on 43 healthy female medical staff including laboratory
      technologists and nurses during an 8-hour working period in our hospital. Low and
      high frequency components (LF and HF, respectively) of the frequency domain,
      recurrence rate (REC%) on recurrence plot analysis, scaling exponents al and a2
      on detrended fluctuation analysis, and approximate entropy (ApEn) were obtained
      from HRV. Both the LF/HF ratio and HF were correlated with al and ApEn. REC% was
      correlated with ApEn and alpha2, whereas alpha2 was correlated only with REC%.
      Although autonomic parameters from the frequency domain are closely related with
      some of the non-linear parameters, it is suggested that a2 and REC% reflect
      different physiological activities.

PMID- 21942086
TI  - [Examination of the patient serum presenting a CEA false high value after cancer
      immuno-cell therapy].
AB  - False positive elevation of carcinoembryonic antigen (CEA) was observed in a 65
      year-old woman who was treated with dendritic cell therapy (DCT) and activated
      lymphocyte therapy (ALT) for intrahepatic cholangiocarcinoma. Three months after
      the initiation of these therapies, her CEA value measured by AIA (TOSOH) began to
      increase without any evidence of worsening of cholangiocarcinoma. CEA was
      measured by several different methods, and only the result measured by AIA was
      high, indicating the presence of a false positive phenomenon. To clarify this
      phenomenon, we evaluated the patient's serum precisely. Gel filtration
      chromatography of her serum showed that CEA was detected in the elution fraction
      of IgG, which was different from the reference samples. Furthermore, this peak
      disappeared after incubation of patient's CEA and HBR-1. The immunoglobulin
      absorption test revealed that CEA value was decreased only after absorption of
      IgG and absorption tests using HBR-1 and MAK-absorbents showed a dramatic
      decrease in CEA value. These findings indicated the presence of IgG type human
      anti-mouse antibodies (HAMA), which interfered the measurement by AIA. Although
      we could not identify the reason why HAMA was produced in this patient, the facts
      that the false positive phenomenon was observed after the initiation of DCT and
      ALT, and that CEA value decreased after theses therapies were discontinued,
      indicated that immuno-modulaton by DCT and ALT may have a close relationship to
      HAMA production. It was probable that DCT and ALT activated preexisting
      heterophile-antibody-producing cells, which stimulated HAMA production. The
      incidence of such false positive reaction of CEA by HAMA in patients with DCT and
      ALT was low, but as the number of the patient with immuno-cell therapy increases,
      the incidence of such phenomenon surely increases. Because HAMA reacts to all
      types of immunoassay, careful attention should be paid to the evaluation of
      laboratory findings in patients undergoing with such immuno-cell therapies.

PMID- 21942088
TI  - Educational courses for physiological function examination at Jichi Medical
      University: practical trainings in ultrasonography.
AB  - To foster work-ready general physicians, Jichi Medical University has developed
      various clinical teaching practices since its foundation. The educational courses
      for clinical laboratory medicine, being one of them, adopt practical trainings in
      ultrasonography, which is essential in practical medicine today. The aims and the
      specifics of the trainings adopted in the seminar of ultrasound and the required
      or the optional subjects of Bedside Learning (BSL) at Jichi Medical University
      are reported.

PMID- 21942089
TI  - [Vascular function tests to assess risk for cardiovascular diseases].
AB  - Ultrasound examination, computed tomography, and/or magnetic resonance imaging
      can be employed to easily assess the severity of atherosclerotic vascular damage
      morphologically. On the contrary, the pulse wave velocity (PWV), pulse wave
      analysis (augmentation index: AI), and/or flow-mediated vasodilatation of the
      brachial artery(FMD) can reveal atherosclerotic functional vascular
      abnormalities. Recent meta analyses demonstrated that PWV and/or AI are markers
      which can be used to predict future cardiovascular events independent of
      conventional risk factors for cardiovascular disease. In this review, we discuss
      the applicability and limitations of vascular function tests.

PMID- 21942090
TI  - [Potential of plasma adiponectin concentrations as a predictive marker for in
      stent restenosis after percutaneous coronary intervention in patients on
      hemodialysis].
AB  - Success of coronary stenting is limited by in-stent restenosis. We aimed to
      determine whether circulating levels of adiponectin could be associated with the
      occurrence of coronary in-stent restenosis in patients with end-stage renal
      disease (ESRD). We enrolled 71 consecutive ESRD patients undergoing hemodialysis
      (mean age: 64.9 +/- 8.9 years; 19 women, 52 men; mean hemodialysis duration: 78.2
      +/- 87.5 months), who received stenting for a single coronary lesion. Plasma
      adiponectin concentrations were measured within one week before coronary
      stenting. Of 71 patients who had received stenting, in-stent restenosis occurred
      in 37 patients (52.1%) within 6 months after stenting. In univariate logistic
      analysis, homeostasis model assessment index of insulin resistance, blood
      hemoglobin, serum concentrations of high density lipoprotein cholesterol or
      triglycerides, and plasma concentrations of insulin or adiponectin were
      significantly associated with coronary in-stent restenosis. In multiple logistic
      regression analysis among these variables, however, only the plasma adiponectin
      concentration was associated with the coronary in-stent restenosis: the odds
      ratio of increase in 1 microg/ml of plasma adiponectin concentration for having
      restenosis was 0.651 (p = 0.001, 95% confidence interval: 0.506-0.839). Patients
      with restenosis had lower plasma adiponectin concentrations than those without
      [6.2 +/- 2.2 microg/ml (2.1-10.4 microg/ml; n=37) versus 27.2 +/- 10.8 microg/ml
      (17.9-79.8 microg/ml; n=34); p = 0.0001]. Circulating adiponectin concentrations
      may be associated with the occurrence of coronary in-stent restenosis in ESRD
      patients undergoing maintenance hemodialysis.

PMID- 21942091
TI  - [Mechanisms of biosynthesis of built-in cofactors].

PMID- 21942092
TI  - [Mechanisms of endocannabinoid-mediated retrograde modulation of synaptic
      transmission].

PMID- 21942093
TI  - [Structures and molecular recognition mechanism of leukocyte immunoglobulin-like
      receptor family].

PMID- 21942094
TI  - [What does Reelin control to regulate neuronal layer formation in the developing
      cerebral cortex?].

PMID- 21942095
TI  - [Regulation of CXCL14/BRAK, a tumor-suppressing chemokine, by MAP kinase subtype
      specific crosstalk].

PMID- 21942096
TI  - [Novel regulatory mechanisms for transcriptional initiation of ribosomal protein
      genes in S. cerevisiae].

PMID- 21942097
TI  - [Exploring for the biological and genetic resources from the uncultivated
      bacteria].

PMID- 21942098
TI  - [Selective chemical labeling and engineering of endogenous cellular proteins].

PMID- 21942099
TI  - [Novel role of RUNX3 in the regulation of p53-mediated apoptosis in response to
      DNA damage].

PMID- 21942100
TI  - [Novel approach for the cell surface molecular interactome using enzyme-mediated
      activation of radical sources (EMARS) reaction].

PMID- 21942101
TI  - Maybe Sophie was right: child welfare evaluation and research. Introduction.

PMID- 21942102
TI  - Methods of evaluating child welfare in Indian country: an illustration.
AB  - The poor quality and quantity of data collected in tribal communities today
      reflects a lack of true community participation and commitment. This is
      especially problematic for evaluation studies, in which the needs and desires of
      the community should be the central focus. This challenge can be met by
      emphasizing indigenous methods and voice. The authors provide an illustration of
      how to do this.

PMID- 21942103
TI  - Context matters: real-world and utilization-focused evaluation strategies to
      support change and improvement in child welfare.
AB  - This article examines the importance of context in evaluative inquiry. Following
      guidelines from real-world and utilization-focused evaluation frameworks, four
      projects are described to illustrate one foundation's pragmatic approach to
      evaluation that values collaboration, methodological appropriateness, and
      utilization. The authors contend that such an approach helps to ensure meaningful
      and actionable results in child welfare because it is responsive to local agency
      information and capacity needs while simultaneously contributing to the knowledge
      base of the field.

PMID- 21942104
TI  - Conducting culturally competent evaluations of child welfare programs and
      practices.
AB  - As the population of the United States has changed over the last two decades, so
      has the population of children who come to the attention of the child welfare
      system, resulting in increasing calls for cultural competence in all aspects of
      child welfare programming and practice. Given the changing demographics among
      children involved in the child weltare system and the increasing need to address
      the racial and ethnic disparities observed in this system, the need for
      culturally competent approaches to evaluate the outcomes of services for children
      and families is essential. This article discusses the challenges in conducting
      culturally competent evaluations and provides strategies to address those
      challenges within a child welfare context.

PMID- 21942105
TI  - Collaborative research in child welfare: a rationale for rigorous participatory
      evaluation designs to promote sustained systems change.
AB  - Expansion of the child welfare evidence base is a major challenge. The field must
      establish how organizational systems and practice techniques yield outcomes for
      children and families. Needed research must be grounded in practice and must
      engage practitioners and administrators via participatory evaluation. The extent
      to which successful practices are transferable is also challenged by the
      diversity of child welfare systems. The U.S. Department of Health and Human
      Services' Children's Bureau funded Quality Improvement Centers (QICs) that were
      designed to promote collaborative, multisite research that would address these
      evaluation needs. This article, based on the findings of a regional and a
      national QIC, describes the challenges facing research collaboration and the
      strategies for achieving success.

PMID- 21942106
TI  - Comparing child protective investigation performance between law enforcement
      agencies and child welfare agencies.
AB  - This study examines the comparative effectiveness of using law enforcement
      agencies for child protective investigation (CPI), in contrast with the
      traditional approach of CPI conducted by the public child welfare agency. The
      analysis uses 2006-2007 data from a natural experiment conducted in Florida to
      show modest differences in performance and cost-efficiency between the two
      approaches to CPI. These findings may have implications for other states
      considering outsourcing CPI to law enforcement.

PMID- 21942107
TI  - Housing services for child welfare-involved families: an initial evaluation using
      observational data.
AB  - This study evaluated the impact of housing services among child welfare-involved
      families using observational data. Propensity score matching with data from the
      National Survey of Child and Adolescent Well-Being compared intact families (n =
      183) who received housing services 12 months after initial investigation to
      nontreated families balanced on characteristics at the time of investigation.
      Results suggested that general housing services failed, on average, to
      effectively address the needs of inadequately housed families.

PMID- 21942108
TI  - Predictors of placement stability at the state level: the use of logistic
      regression to inform practice.
AB  - Placement instability is often associated with a number of negative outcomes for
      children. To gain state level contextual knowledge of factors associated with
      placement stability/ instability, logistic regression was applied to selected
      variables from the New Mexico Adoption and Foster Care Administrative Reporting
      System dataset. Predictors identified in the model are consistent with previous
      research, reliable across time periods, and informative to the understanding of
      potential risk/protective factors of placement stability/instability specific to
      the New Mexico child welfare agency.

PMID- 21942109
TI  - Organizational factors and the implementation of family to family: contextual
      elements of systems reform.
AB  - In efforts to reform the child welfare system, agency leaders must involve staff
      at all levels; yet, little research has been done to determine which
      organizational factors encourage or inhibit staff engagement. Employees from an
      urban child welfare agency were invited to complete a survey regarding
      organizational effectiveness and its influence on reform efforts. The results
      show how these findings can be used by managers to improve practice, specifically
      through increased information sharing with stakeholders.

PMID- 21942110
TI  - Colorectal cancer.

PMID- 21942111
TI  - The effect of combining interferon-alpha and gefitinib in human colon cancer cell
      lines.
AB  - BACKGROUND AND AIMS: Interferon-alpha (IFN-alpha) treatment is associated with up
      regulation of epidermal growth factor receptor (EGFR) expression and marked
      growth inhibition of colon cancer cell lines. We aimed to determine the effect of
      combining IFN-alpha and gefitinib in the growth of human colon cancer cell lines.
      METHODS: Two human colon cancer cell lines SW480 and LOVO were treated with IFN
      alpha alone or gefitinib alone or IFN-alpha plus gefitinib. Proliferation of
      colon cancer cells was measured by methyl thiazolyl tetrazolium (MTT) assay; the
      apoptosis rate was analysed by flow cytometry (FCM). The expression of XIAP, XAF1
      mRNA was detected by RT-PCR and the expression of XlAP XAF1 protein was detected
      by western blotting. RESULTS: Methyl thiazolyl tetrazolium showed that IFN-alpha,
      gefitinib and IFN-alpha plus gefitinib significantly inhibited SW480 and LOVO
      cells in a dose-dependent manner (p < 0.05). The FCM revealed that lFN-alpha,
      gefitinib and IFN-alpha plus gefitinib could markedly upgrade the apoptosis rate
      (p < 0.05). The expression of XIAP mRNA down-regulated markedly (p < 0.05) while
      the expression of XAF1 mRNA up-regulated significantly (p < 0.05). The expression
      of XIAP protein was down-regulated markedly (p < 0.05) while the expression
      ofXAF1 protein was up-regulated significantly (p < 0.05). CONCLUSION: IFN-alpha
      promotes the antiproliferaative effect of gefitinib on human colon cancer cell
      lines and the mechanism may be related to up-regulation expression of EGFR by IFN
      alpha.

PMID- 21942112
TI  - Dengue virus serotypes in Jamaica, 2003-2007.
AB  - BACKGROUND: Dengue virus (DENV) infection is increasing in prevalence and
      severity globally. The severity of dengue is influenced by several factors
      including the immune response, viral and host genetic factors. METHOD: The DENV
      serotypes were determined in 770 serum samples from dengue immunoglobulin (Ig) M
      antibody positive (n = 469), dengue IgM negative (n = 185) and dengue antibody
      negative (n = 116) patients with suspected dengue who presented during (n = 150)
      or after (n = 620) the acute phase of illness during 2003-2007. Dengue antibodies
      were detected by enzyme-linked immunosorbent assays and DENV RNA by reverse
      transcriptase-polymerase chain reaction (RT-PCR) performed on serum and cell
      culture supernatants of C6/36 mosquito cells inoculated with acute phase serum (n
      = 150). RESULTS: Based on serological profiles, 41% of acute phase sera and 66%
      of post acute sera were from patients with current primary or secondary dengue,
      while 41% and 35% of acute and post-acute phase sera, respectively, were from
      patients with secondary dengue or past exposure only. Dengue virus RNA was found
      in 20/770 samples (2.6%). Only 1.5% (9/620) of sera collected after the acute
      phase of illness tested positive for DENV RNA compared with 2.6% (4/150) of sera
      collected during the acute phase and 7.3% of cell culture supernatants inoculated
      with acute phase serum (11/150, p = 0.001). All four serotypes including DENV-1
      (3/20, 15%), DENV-2 (7/20, 35%), DENV-3 (3/20, 15%) and DENV-4 (7/20, 35%) were
      identified over the five-year period. These results also showed that DENV-1, 2
      and 4 were present during 2007 and that DENV-2 and DENV- 4 were the likely
      causative viruses of the 2007-2008 dengue outbreak in Jamaica. The three strains
      of DENV-3 were isolated from infants less than three years of age with primary
      infection during 2006. CONCLUSION: This study highlights the increasing threat of
      dengue and severe dengue disease to the Jamaican population. Preventative
      measures including laboratory surveillance and vector control should be strictly
      maintained at the highest level.

PMID- 21942113
TI  - Molecular epidemiology of dengue in Jamaica dengue virus genotypes in Jamaica,
      2007.
AB  - The genotypes of dengue viruses (DENV) isolated from patients with dengue in
      Jamaica during 2007 were determined using DNA sequencing and phylogenetic
      analysis of the C-prM gene junction. The 17 DENV analysed included strains of
      DENVserotypes 1 (DENV-1, n = 3), DENV-2 (n = 7) and DENV-4 (n = 7). All strains
      ofDENV-1 were classified as genotype III, while 1 of 7 strains of DENV-2 belonged
      to the Asian American/Asian genotype, genotype I/III (Jamaica genotype), 2 were
      genotype V, the American genotype and 4 strains clustered with reference strains
      belonging to genotype IV. The 6 DENV-4 strains from Jamaica and the control
      strain clustered together in a separate clade from Caribbean/American reference
      strains, which belong to genotype II and Asian strains, classified as genotypes I
      and III. There has been little evolution in the DENV-1 strains circulating in
      Jamaica over the years and this might reduce the risk of outbreaks due to this
      serotype. In contrast, the high genetic diversity in strains of DENV-2 viruses in
      circulation, the presence of more recently introduced genotypes and a new clade
      of DENV-4 might contribute to the epidemic potential of these DENV serotypes.
      These preliminary data clearly indicate the need to maintain laboratory
      surveillance, and other control measures against hyperendemicity of dengue in
      Jamaica.

PMID- 21942114
TI  - Dengue HLA associations in Jamaicans.
AB  - BACKGROUND: Polymorphisms in the human leukocyte antigen (HLA) genes might
      predispose certain individuals to dengue fever (DF) and the severe forms of the
      disease: dengue haemorrhagic fever/ dengue shock syndrome (DHF/DSS). SUBJECTS AND
      METHOD: A DNA-based HLA typing method was used to determine the HLA class I and
      II alleles in 50 patients with dengue, including 45 cases of DF 5 cases of DHF
      and 177 healthy individuals in Jamaica. RESULTS: HLA-A*24 and - DRbeta5*01/02
      were significantly associated with dengue infection while possession of HLA-A*23,
      -CW*04, -DQbeta*02, -DQbeta*03 and DQbeta*06 were protective. No other
      significant associations were found after correction for the number of alleles
      tested at each HLA-locus. CONCLUSION: This is the first study to report a
      significant association with HLA-A*24 and DF although this allele is associated
      with DHF and DSS in Vietnamese patients. The other HLA associations observed in
      the Jamaican cohort also are different from those reported in other ethnic
      groups. Further studies which involve larger numbers of patients with DHF and
      explore functional aspects of HLA allelic associations with dengue in Jamaicans
      are necessary.

PMID- 21942115
TI  - Effect of a cholesterol rich diet, recurrent infection and possible treatment
      modalities on the pulmonary vascular system: an experimental study.
AB  - OBJECTIVE: Infection may lead to inflammation, atherosclerosis and thrombotic
      vascular events. The atherosclerotic effect of hypercholesterolaemia on the
      vascular system is well-known. However, limited studies were done on the
      therapeutic and preventative agents. The aim of this study was to investigate the
      effects of infection and cholesterol rich diet combined with an antibiotic, anti
      inflammatory agent and red wine on the pulmonary vascular system. METHODS: Fifty
      nine rats were evaluated. Six groups were created: Control-Group I (n = 10);
      infection --Group II (n = 9), infection-cholesterol rich diet--Group III (n =
      12), infection-cholesterol rich diet-cefepime--Group IV (n = II); infection
      cholesterol rich diet-diclofenac potassium--Group V (n = 9); infection
      cholesterol rich diet and red wine--Group VI (n = 8). Blood samples of rats were
      collected for cholesterol analysis every month. Sections of central pulmonary
      arteries were examined for thickness of the intima and medial wall by
      computerised image analysis. RESULTS: There was a statistically significant
      difference in serum cholesterol levels and in thickness of the intima between the
      groups (p = 0.000). The rest of the groups had more intimal thickening than Group
      I (p = 0.000). Group III had thicker intima than Groups IV and V (p = 0.009, p =
      0.011 respectively). There was no significant difference between the groups in
      thickness of media (p = 0.432). CONCLUSION: Infection and cholesterol rich diet
      have a synergistic effect on atherosclerosis in pulmonary arteries. However
      antibiotics and anti-inflammatory agents could be useful in prevention.

PMID- 21942116
TI  - Poverty, folate deficiency, human immunodeficiency virus and ulcerated vulval
      sexually transmitted diseases in Jamaica.
AB  - Sexually transmitted genital ulcerative conditions are declining in Jamaica. The
      rates at present are far lower than that seen in the 1950s-1960s. Review of the
      records of the national Comprehensive Clinic has revealed that all of the major
      sexually transmitted conditions (Syphilis, Lymphogranuloma Venereum (LGV),
      Chancroid, Granuloma Inguinale and Herpes Simplex) have declined but have had
      three peaks between 1958 and 2000. Closer review seems to suggest that the peaks
      were associated firstly with poverty in the 1960s and 1970s and to the HIV
      epidemic in the 1980s and early 1990s. There are also smaller spikes which appear
      to be associated with periods of environmental disasters, with a possible
      association with folate deficiency. This is apparent for the bacterial and
      chlamydial conditions as well as viral conditions such as Herpes simplex.

PMID- 21942117
TI  - The predictive value of urinary vanillylmandelic acid testing in the diagnosis of
      phaeochromocytoma at the University Hospital of the West Indies.
AB  - OBJECTIVE: To investigate the positive predictive value (PPV) of urinary
      vanillylmandelic acid (VMA) testing in the diagnosis of phaeochromocytoma and to
      describe the features associated with phaeochromocytoma at the University
      Hospital of the West Indies (UHWI). SUBJECTS AND METHODS: There were 551 VMA
      tests performed from January 2003 to June 2009 and 122 tests in 85 patients were
      elevated (ie > or = 35 micromol/24 hr). The study patients were categorized as:
      (i) 'surgical' (5 patients who underwent surgery) or (ii) 'non-surgical'
      (remaining 80 patients). Forty medical charts (out of 85) were reviewed using a
      standardized data extraction form. RESULTS: The median age for patients in the
      non-surgical group (with charts reviewed, n = 35) was 36 years (range 9-70) and
      the median VMA was 43 micromol/24 hr (IQR 38-51). Of these patients, 83% had one
      or no symptom typical of phaeochromocytoma. In the surgical group the median VMA
      was 58 micromol/24 hr (IQR 44-101); phaeochromocytoma was confirmed
      histologically in 3 patients, all of whom had several symptoms typical of
      catecholamine excess. VMA testing had a PPV of 8%, specificity of 79% and
      sensitivity of 100%. CONCLUSIONS: VMA testing at UHWI has poor specificity and
      high sensitivity. These results contrast with international data showing that VMA
      testing is poorly sensitive but highly specific. The use of assays with higher
      specificity (eg plasma or urinary metanephrines) may represent a more cost
      effective approach to biochemical screening at UHWI.

PMID- 21942118
TI  - Impact of yoga on haemodynamic function in healthy medical students.
AB  - OBJECTIVES: Yoga improves cardiovascular health in both healthy individuals and
      those with diagnosed heart disease. This study compares changes in some
      cardiovascular parameters before and after the practice of Yoga in healthy
      medical students. METHODS: Sixty-four healthy medical students (57 females and 7
      males), mean age 21.3 +/- 2.6 years, attending a Special Study Module 'Role of
      Dhyana Yoga in Stress Management', participated in this study. Systolic (SYS) and
      Diastolic (DIA) blood pressure, Heart Rate (HR), Stroke Volume (SV), Cardiac
      output (CO), Total Peripheral Resistance (TPR), Interbeat Interval (IBI), Left
      Ventricular Ejection Time (LVET), Arterial Compliance (Cwk) and Ascending Aorta
      Impedance (Zao) were measured before and after six weeks of yogic exercises.
      Various exercises included asanas (Postures), pranayama (Breathing), and dhyana
      (Meditation). Data were analyzed using Stata for Windows. RESULTS: Two-tailed
      paired t-test revealed that practice ofyoga caused significant increases in HR (p
      < 0.05), SV (p < 0.01), CO (p < 0.001) and Cwk (p < 0.01) and decreases in TPR (p
      < 0.001), IBI (p < 0.05) and Zao (p < 0.001) after practising yoga for 6 weeks as
      compared to before yoga practice. No significant differences were, however
      observed in SYS, DIA, Mean arterial blood pressure (MAP) and LVET CONCLUSIONS:
      Practice of yoga even for a short period showed ability to improve most of the
      cardiovascular functions. Regular practice of yoga for a longer period may
      further improve these functions and possibly result in improved management of
      their daily stress.

PMID- 21942119
TI  - The outcome of febrile neutropenic episodes in paediatric oncology at the Wendy
      Fitzwilliam Paediatric Hospital.
AB  - OBJECTIVE: To evaluate the incidence, presentation, treatment and outcome of
      febrile neutropenic episodes of patients treated at the Wendy Fitzwilliam
      Paediatric Hospital (WFPH) in Trinidad and Tobago. METHODOLOGY: Using a
      retrospective cohort method, the records of all the patients registered at the
      Paediatric Oncology Unit at The WFPH, receiving chemotherapy for haematological
      or solid tumour malignancies from May 2001 to April 2008 and having episodes of
      febrile neutropenia were analysed. RESULTS: Seventy one episodes of febrile
      neutropenia were analysed from the 36 patient records. Episode frequency ranged
      from 1 to 5. The mean duration of febrile neutropenic episodes was 5.01 days (+/-
      SD 5.2), with range from 1-25 days. Acute Lymphoblastic Leukaemia (ALL) accounted
      for 43.7%. The mean WBC for the study population was 0.88 x 10(9)/L (+/- SD
      0.61), with the mean absolute neutrophil count (ANC) at 0.16 x 10(9)/L (+/- SD
      0.23). Antifungal therapy was used in 6 cases and the incidence of blood culture
      positive sepsis was 8.5%. Complete resolution occurred in 65 episodes CONCLUSION:
      Febrile neutropenia episodes treated at the WFPH have a very favourable outcome
      (91.5%). The further analysis of the relationships found in this study between
      the total white blood cell count at presentation and the duration of
      antimicrobial therapy, the duration of the febrile neutropenic episodes and
      outcome is needed.

PMID- 21942120
TI  - Are parents in tune with music their adolescent children enjoy? Are there missed
      opportunities for sexual and reproductive health dialogue?
AB  - The perspectives of adolescents were solicited on the issue of sexual and
      reproductive health messages they received through dancehall music as well as
      their perceptions of parents' views of such messages and adolescents' indulgence
      with this genre of music. METHODS: This sequential mixed methods study was
      completed in 2008. The study's qualitative component was summarized as the novel
      ALODAC (Ask, Listen and Observe, Discuss, Analyse and Confirm) model, involving a
      series of steps to engage adolescents 10-19 years to share their perspectives on
      sexual and reproductive health messages enunciated in the dancehall music to
      which they listen. The quantitative component saw 1626 adolescents in public
      schools responding to an interviewer-administered questionnaire which included
      questions about their families and how they respond to dancehall content. Five
      messages determined from content analysis of songs on adolescents' music menu
      were used to initiate discussions with adolescents about the issues. RESULTS:
      Almost equal proportions of respondents in the survey lived with either their
      mothers (37.3%) or both parents (35.6%). Most adolescents reported enjoying
      dancehall music and learning specific messages even when some parents were
      against use of such music. There were significant gender differences observed
      regarding perceptions about parents agreement with lyrics on transactional sex (p
      < 0.001), prevention of pregnancy (p < 0.01), condom use (p < 0.01) and multiple
      relationships (p < 0.01). CONCLUSIONS: Whether or not parents are in tune with
      the music their adolescent children listen to does not seem to affect the
      pleasure and lessons adolescents gain from this medium. Opportunities for
      discussing sexual issues common in Jamaican dancehall music exist but are missed.

PMID- 21942121
TI  - The Jamaican adolescent's perspective on violence and its effects.
AB  - The Caribbean and in particular Jamaica is experiencing an epidemic of violence
      which adversely affects its youth who are the main perpetrators and victims.
      Early and protracted exposure to violence is part of the socialization experience
      that results in violence-related behaviours. This paper examines the impact of
      the early and sustained exposure to violence on the attitudes and behaviours of
      Jamaican adolescents from their perspective. An analysis of qualitative data
      collected from three studies between 2005 and 2009 among adolescents across
      Jamaica was conducted using the recurrent theme approach. Exposure to violence
      was common and increased with age and lower socioeconomic status and was most
      marked among marginalized inner city youth. While attitudes and behaviours in
      response to the violence varied among adolescents, there was a "dose response
      effect" in relation to age and lower social status. It is necessary to alter the
      socialization process in order to break the cycle of violence through wide
      ranging interventions that touch on every aspect of the spheres of influence in
      the life of Jamaican adolescents.

PMID- 21942122
TI  - Temporomandibular joint ankylosis in a Nigerian teaching hospital.
AB  - Twenty-six patients (12 males and 14 females) between two days and 41 years old
      with temporomandibular joint ankylosis were retrospectively reviewed. Thirty
      three joints were involved; 19 unilateral and six bilateral. The aetiologies were
      trauma, 69.2%; infection, 15.4%; unknown, 11.5% and congenital, 3.9. The
      majority, 31 were intracapsular while the remaining two joints were extracapsular
      51.6% were limited to the condyle, 32.2% extended to the coronoid process and the
      zygomatic, 9.7% extended to the sigmoid notch while the remaining 6.5% had
      maxillomandibular fusion. Tracheostomy (48%) was the most common mode of
      intubation. Gap arthroplasty was carried out in 20 joints while 11 joints had
      interposition arthroplasty. Postoperative complications were seven anterior open
      bite, three facial nerve weakness, three infections and two recurrences.

PMID- 21942123
TI  - Compliance with intramuscular penicillin prophylaxis in children with sickle cell
      disease in Jamaica.
AB  - OBJECTIVE: Penicillin prophylaxis is important in the defence against invasive
      pneumococcal disease in sickle cell disease (SCD). Penicillin may be administered
      by the oral route or by the intramuscular (IM) route. Compliance with the oral
      route, although difficult to assess, has been reported to be highly variable and
      often poor. We sought to determine the compliance rate with intramuscular
      penicillin (IM) prophylaxis in children with sickle cell disease. METHODS:
      Children followed at the Sickle Cell Unit in Jamaica were recruited. Good
      compliance was deemed if patients received at least 10 injections over the
      preceding 12-months. Children on IM prophylaxis for less than a 12-month period
      were deemed to be compliant if they received 80% of injections since commencing
      prophylaxis. RESULTS: Data were available for 78 (HB SS 73; male 42) patients
      attending the clinic during the period of observation. Sixty-nine (88.5%) of the
      children were compliant with IMpenicillin prophylaxis. CONCLUSION: This study
      reports a high compliance (88.5%) to IM penicillin prophylaxis which was
      associated with an incidence rate of invasive pneumococcal disease lower than
      what is seen in other comparable studies, reflecting the route of administration.
      Intramuscular penicillin prophylaxis, despite challenges, is a practical option.
      It can contribute to better patient compliance and thus significantly impact
      global rates of invasive pneumococcal disease and its complications in children
      with SCD and other similar conditions.

PMID- 21942124
TI  - Subjective well-being of adults with homozygous sickle cell disease in Jamaica.
AB  - OBJECTIVES: This study compared the subjective well-being of adults with
      homozygous sickle cell (SS) disease to a matched group of healthy adult peers.
      The differential influence of sociodemographic factors on the subjective well
      being of Sickle Cell patients was also examined. METHODS: The Ferran and Powers
      Quality of Life Index and the Positive and Negative Affect Schedule were used to
      assess subjective well-being. Seventy-five homozygous sickle cell (SS) disease
      patients and sixty-seven matched controls (adults with normal haemoglobin: AA)
      from the Sickle Cell Disease Cohort Study in Jamaica were interviewed. Analysis
      of variance (ANOVA) was used to examine differences between the groups. RESULT:
      Patients with Sickle cell (SS) disease were less satisfied than matched controls
      with their lives overall, their health and functioning, social and economic
      situation and psychological functioning. Sickle cell disease patients reported
      lower levels of positive affect but similar levels of negative affect as
      controls. Unemployed sickle cell disease patients were less satisfied than all
      other adults with their lives overall, health and functioning, psychological
      functioning and social and economic situation. Sickle cell disease patients with
      lower occupational status were less satisfied with their family life than all
      other adults. CONCLUSIONS: These findings suggest that subjective well-being is
      compromised in patients with homozygous sickle cell disease. These patients may
      benefit from interventions designed to improve their subjective well-being.

PMID- 21942125
TI  - Updates on current advances in gene therapy.
AB  - Gene therapy is the attempt to treat diseases by means of genetic manipulation.
      Numerous challenges remain to be overcome before it becomes available as a safe
      and effective treatment option. Retroviruses and adenoviruses are among the most
      commonly used viral vectors in trials. The retrovirus introduces the gene it
      carries into the target cell genome while the adenovirus introduces the gene into
      the target cell nucleus without incorporating it into the target cell genome.
      Other viral vectors such as adeno-associated viruses, pseudotyped viruses and
      herpes simplex viruses, are also gaining popularity. Proposed non-viral methods
      for gene transfer include physical methods and the employment of chemical vectors
      (lipoplexes, polyplexes and inorganic nanoparticles). Recent studies have
      investigated potential applications of gene therapy in correcting genetic
      diseases, treating malignant disorders and for treatment of other diseases.
      Trials on gene therapy for SCID and Leber's congenital amaurosis have achieved
      considerable success, but the widely publicized adverse reaction in X-linked SCID
      patient receiving gene therapy raised concerns for safety profile of gene
      therapy. For that, several methods of improving safety and efficacy of gene
      therapy have been proposed. At present, the three main gene therapy strategies
      for treatment of cancer are application to oncolytic viruses, suicide-gene
      therapy and gene-based immunotherapy. Gendicine, the first approved anticancer
      drugs based on the use of gene therapy principle, is based on the use of
      oncolytic viruses. More evidence for wider clinical applications of gene therapy
      are expected as more gene therapy studies progress from the preclinical phase to
      clinical trial.

PMID- 21942126
TI  - Factors related to obstetric third and fourth degree perineal lacerations in a
      Jamaican cohort.
AB  - OBJECTIVES: The aim of this study was to identify significant and modifiable risk
      factors associated with obstetric third and fourth degree perineal lacerations
      and to produce recommendations that may reduce their morbidity and prevalence.
      METHODS: This is a retrospective case control study performed between March 2004
      and March 2008. All patients diagnosed with third and fourth degree perineal
      lacerations were identified (cases) along with randomly assigned controls who
      delivered during the same time period. Nineteen cases and 38 controls were
      identified giving a total of 57 patients. Each patient's hospital record was
      collected and the data extracted. RESULTS: When analysed for weight greater than
      or equal to 3.5 kg versus birthweight of less than 3.5 kg, the difference between
      cases and controls was found to be statistically significant, with a p-value of
      0.012. Of the cases, 21% had an operative delivery (forceps or vacuum) whereas
      only 2.6% of the controls had an operative delivery. This was found to be
      statistically significant (p = 0.011). CONCLUSION: This study has shown that the
      two main factors related to the obstetric third and fourth degree perineal
      lacerations were babies weighing more than 3.5 kg and the use of forceps or
      vacuum to assist with deliveries. These high risk patients should be attended to
      by the most senior staff that is available.

PMID- 21942127
TI  - Preparation for a medical mission to Jamaica--pharmacy's perspective.
AB  - OBJECTIVE: To describe preparation of a medical mission from a pharmacy team's
      perspective. METHODS: Essential components of the medication planning process
      include the development of a separate medication budget, a medication formulary
      (based on needs assessment and availability) and acquisition of medications and
      medical supplies. RESULTS: For the medical mission to Jamaica, medications are
      often purchased or donated from various locations, including retail pharmacies,
      drug wholesalers, medication drives, pharmaceutical companies, and medication
      assistance programmes specific to medical missions. It is essential to understand
      the policy associated with the importation of medications which can be found in
      the Approval Process for Food, Drugs, Cosmetics, Medical devices, Precursor
      Chemicals and Narcotics, a paper developed by the Ministry of Health, Jamaica.
      CONCLUSIONS: Elevated levels of planning and preparation are required for the
      medical mission to Jamaica to be a success; assistance and cooperation is
      necessary from all members of the interdisciplinary medical mission team. It is
      imperative to plan ahead, be organized and equipped to handle unexpected
      situations so that quality care can be delivered to the patients to be served.

PMID- 21942128
TI  - Epidemic management: a Caribbean university's response to the 2009 H1N1 outbreak.
AB  - BACKGROUND: In June 2009, the World Health Organization (WHO) declared a global
      influenza pandemic (1). During the throes of the epidemic, the Caribbean region
      recorded 22 deaths and 350 hospitalizations. Jamaica reported most of the deaths
      in the region--7, followed by Trinidad and Tobago--5 and Barbados--3; the
      remaining 7 deaths occurred in other Caribbean countries (2). In June, Jamaica
      reported its first case (3) and some three months later in September 2009, The
      University of the West Indies (UWI) Mona Campus experienced an outbreak of the
      2009 H1N1 virus infection. As one of the three main Campuses of the leading
      tertiary institution in the English-speaking Caribbean (others being in Trinidad
      and Tobago and Barbados in addition to an 'Open Campus' which serves the non
      Campus territories), the UWI Mona Campus serves some 15 000 students. These
      students originate mainly from the Caribbean; North American and African students
      also comprise the student population. The University Health Centre provides
      primary care services to a community of students, staff (3000) and their
      dependents, retirees, visiting staff and students.

PMID- 21942129
TI  - The need for gender specific tobacco control strategies KAP survey findings on
      environmental tobacco smoke exposure among women in the reproductive age group.
AB  - OBJECTIVE: The study was done to assess knowledge, attitudes and practices of
      women within the child bearing age with regard to smoking and exposure to
      environmental tobacco smoke (ETS) on children's health. SUBJECTS AND METHODS: A
      cross-sectional study with quantitative and qualitative components was designed
      to collect data from women in the child-bearing age. The sample comprised of
      persons from the two largest combined family planning and antenatal clinics in
      Kingston, Jamaica. RESULTS: The women surveyed had a fair level of knowledge
      about ETS health risks, negative attitudes to smoking in general, and most
      supported a ban on smoking in public places. Significant knowledge differences
      existed between young and older women and between smokers and non-smokers.
      CONCLUSION: Women with the highest level of knowledge were the non-smokers: of
      the low knowledge score group (current smokers), 50% were in the 15-24-year age
      range. There is a need for more public education on smoking and the consequences
      of environmental tobacco smoke exposure on children's health.

PMID- 21942130
TI  - Acute limb ischaemia in a septic patient with diabetic ketoacidosis.
AB  - This is a patient with septicaemia and diabetic ketoacidosis who developed an
      acute ischaemic lower limb from an arterial thrombus. The patient had decreased
      protein S function.

PMID- 21942131
TI  - Acute fulminant myocarditis and the 2009 pandemic influenza A virus (H1N1).
AB  - The 2009 Pandemic Novel Influenza A [HIN1] resulted in mild disease mostly but
      severe cases and death were associated with pneumonia, respiratory failure and
      multi-organ failure. We present a case of severe disease with acute heart failure
      and arrhythmia due to fulminant myocarditis in a 50- year old obese man with
      diabetes mellitus.

PMID- 21942132
TI  - Challenges of airway management in a patient with temporomandibular joint
      ankylosis complicating forceps delivery--a case report.
AB  - Ankylosis of the temporomandibular joint following forceps delivery is a rare
      anomaly. The aetiopathogenesis involves wrongful application of the forceps or
      forceful closure of the forceps handle against the condyle with haemathrosis,
      organisation and subsequent ankylosis. Because of the lack of epidemiological
      data, there is little information about the true incidence and the management of
      this rare anomaly. The purpose of this presentation is to report the challenges
      encountered in the airway management of a six-year old female with right
      temporomandibular joint ankylosis following forceps delivery in a private
      hospital setting.

PMID- 21942133
TI  - Abdominal pain: a symptom of levodopa end of dose wearing off in Parkinson's
      disease.
AB  - Long-term levodopa use is associated with the "End of Dose Wearing Off" (EODWO)
      phenomenon wherein Parkinsonian symptoms return before a patient's next scheduled
      dose of levodopa. Wearing off symptoms may include a variety of autonomic,
      emotional, motor, psychological and sensory abnormalities. Abdominal pain may be
      an important wearing off symptom as an early indicator of the development of
      EODWO in Parkinson's disease (PD) patients. In this report, we present two
      patients on levodopa therapy for PD who developed acute abdominal pain as a
      symptom of EODWO.

PMID- 21942134
TI  - Successful treatment for a case of near-fatal secondary adrenal insufficiency.
AB  - A thirty-six-year old female with shock was found to be unconsciousness a few
      days after developing a respiratory infection. Her past medical history included
      autoimmune hypothyroidism. Her state of shock was not controlled by massive fluid
      resuscitation with a vasopressor and antibiotics. However an infusion of 250 mg
      methylprednisolone dramatically improved her shock state. Further examination
      indicated secondary acute adrenal insufficiency. Adrenal insufficiency may
      complicate other endocrine disorders. Accordingly, a physician should consider
      hypoadrenocorticism, when patients are in a state of refractory shock in spite of
      massive infusion with a vasopressor especially in patients with other endocrine
      disorders.

PMID- 21942135
TI  - A rare case of emphysematous pyelonephritis within a horseshoe kidney.

PMID- 21942136
TI  - A 10-year unsuspected lumbar schwannoma: a case report.
AB  - One case of unsuspected schwannoma is reported in a 69-year old man with chronic
      lumbosacral pain. The tumour had been mistaken for a lumbar lipoma for a decade.
      The definitive diagnosis was established after surgery based on the
      characteristic histopathological findings. The purpose of this report is to alert
      primary care physicians to peripheral sheath nerve tumours, in addition to
      highlight the role of pain and image features in the suspicion of tumours with
      long-term evolution.

PMID- 21942137
TI  - Prevalence and antimicrobial susceptibility pattern of pathogens isolated from
      patients with juvenile periodontitis in Jamaica: a prospective multi-centre study
      of 15 cases over a 15-year period.
AB  - Prevalence and antimicrobial susceptibility pattern of most frequent pathogens
      isolated from patients treated with juvenile periodontitis at three separate
      dental centres in Jamaica from 1989 to 2003 were studied. Swabs were taken from
      these patients periodontal pathologic pocket or root of most of their teeth with
      active disease processes. These swabs were processed at the microbiology
      department of the University Hospital of the West Indies Kingston, Jamaica and
      the Microbiology laboratory, School of Veterinary Medicine, Faculty of Medical
      Sciences, University of the West Indies, St. Augustine, Trinidad and Tobago. The
      identification of the micro-organisms from positive cultures and their
      antimicrobial susceptibility profile were performed using standard
      microbiological procedures and dick diffusion (Kirby-Bauer) methods. Over 80% of
      the patients were females. The most frequent micro-organisms isolated were
      Enterobacter (40.5%), followed by Klebsiella species (19%) and Acinetobacter
      species (10.8%). Actinobacillus actinomycetemcomitans, a widely known key
      pathogen in juvenile periodontal diseases was encountered only in 5.4% (2/37) of
      the cases in this study The most frequent organism isolated were still highly
      susceptibility to the commonly used and available antimicrobials such as
      amoxycillin/clavulanate, trimethoprim/sulphamethoxazole, chloramphenicol and
      aminoglycosides. The most frequent pathogens encountered in this study were
      totally different from what obtains in other places. There is the need to be
      aware of microbes in other countries during the microbiology investigations
      ofjuvenile periodontitis and that the antimicrobial chemotherapy should always be
      based on susceptibility test results. Surgical treatment for mechanical
      debridement of the site and bone grafting with guided tissue regeneration should
      be mandatory in conjunction with specific antimicrobial chemotherapy

PMID- 21942138
TI  - Ameloblastoma in Jamaica--predominantly unicystic: analysis of 47 patients over a
      16-year period and a case report on re-entry cryosurgery as a new modality of
      treatment for the prevention of recurrence.
AB  - OBJECTIVE: To analyse all the cases of ameloblastoma seen in the two major public
      Hospitals in Jamaica over a 16-year period, and to compare the results with what
      has been previously documented by other authors in the literature. A new
      treatment modality for prevention of recurrence of ameloblastoma is described.
      SUBJECTS AND METHODS: The case files of patients histologically diagnosed to have
      ameloblastoma at both the Kingston Public Hospital and Cornwall Regional Hospital
      in Jamaica from 1980 to 1995 were retrieved and information about this
      odontogenic tumour was documented. The analysis revealed that uncystic
      ameloblastoma was predominant (95%) and solid ameloblastoma was about 5%. It was
      not therefore surprising that the average age in the study was 29.1 years, with a
      peak in the 10-19-year age group. No peripheral ameloblastoma was diagnosed.
      RESULTS: A total of 47 new cases of ameloblastoma was recorded between 1980 and
      1995. This number accounted for 16.03% of all jaw bone lesions in Jamaica and
      38.2% of jaw bone lesions of odontogenic origin during this period. These cases
      of ameloblastoma accounted for 67% of odontogenic tumours with the exception of
      the odontomas. The mean age was 29.1 (range 13-67) years. The male:female ratio
      was 1:1.14). Only 3 cases involved the maxilla. Of significance, is the case of
      bilateral ameloblastoma with no continuity to the anterior region, and also the
      case of unilateral involvement of the mandible and the maxilla in the same
      patient. Re-entry cryosurgery (a procedure in which cryosurgery is done after a
      specified period from the primary surgical procedure) after excisional biopsy of
      a relatively small cystic ameloblastoma of the maxilla was negative for
      recurrence. CONCLUSION: The clinicopathological presentation of ameloblastoma in
      Jamaica is not different from what has been documented by other authors
      throughout the world; however; we report two unique cases --a case of bilateral
      ameloblastoma of the mandible and a case of unilateral involvement of the
      mandible and maxilla in the same patient. We suggest that re-entry cryosurgery
      before recurrence be considered in the management of ameloblastoma for the
      prevention of recurrence.

PMID- 21942139
TI  - Proposal for suicide prevention in the United States based on the suicide rates
      by age group in recent years.

PMID- 21942140
TI  - An examination of further measures to deal with anxiety disorders in the elderly:
      a review of the literature indicated the importance of such measures in Japan.

PMID- 21942141
TI  - CMS rule raises bar on quality.

PMID- 21942142
TI  - CLABSI reduction projects with a twist.

PMID- 21942143
TI  - Accreditation field report.

PMID- 21942144
TI  - Florida hospitals link to improve surgical care.

PMID- 21942145
TI  - Two states put radiology on patient safety radar.

PMID- 21942146
TI  - OB/GYN gearing up for QI push?

PMID- 21942147
TI  - TJC readies new standard for ORYX measures.

PMID- 21942149
TI  - Communication is key to successful transitions.

PMID- 21942148
TI  - To succeed, hospitals improve transitions of care.
AB  - The emphasis on preventing readmissions and emergency department visits after
      patients are discharged from the hospital makes it imperative for hospitals to
      improve transitions from one level of care to another. Communication between
      levels of care is essential. Patients and family members should be involved in
      planning for post-acute care. Case management departments should be adequately
      staffed so case managers can spend the time necessary to ensure a successful
      discharge. Follow up with accepting facilities and patients and families ensures
      a smooth transition.

PMID- 21942150
TI  - Rule emphasizes quality and cost savings.
AB  - The Centers for Medicare and Medicaid Services (CMS) emphasizes improving quality
      and efficiencies across settings in the Inpatient Prospective Payment System
      (IPPS) final rule for 2012. Hospitals will receive a 1% market basket increase in
      reimbursement. CMS announced a Medicare spending-per-beneficiary measures that
      will be used in the Value-Based Purchasing program and the Hospital Inpatient
      Quality Reporting program. CMS is adding new quality measures involving infection
      control in 2014 and 2015.

PMID- 21942151
TI  - LTACH liaison aids appropriate level of care.
AB  - The long-term acute care liaison at Pennsylvania State University Milton S.
      Hershey Medical Center identifies patients eligible for a long-term acute care
      hospital (LTACH) stay and coordinates their transition. The LTACH liaison works
      with the case management and social work staffto identify patients early in the
      stay and give families information they can use to make an informed decision
      about a facility. The liaison follows up with the LTACH treatment team to ensure
      that they have all the information they need and feel comfortable about the
      treatment plan. As a result of the program, the hospital has increased the number
      of patients it transfers to LTACHs each month from about 18 to about 30.

PMID- 21942152
TI  - The CM leader's role in recruitment and retention.

PMID- 21942153
TI  - Coaching helps cut readmissions.
AB  - A heart failure and acute myocardial infarction (AMI) readmission reduction
      program at Saint Joseph-London Hospital in London, KY, has reduced 30-day
      readmissions from 27.7% to 15.9% for heart failure and from 23% to 10 percent for
      AMI. A transition coach visits patients in the hospital and sees them in the
      hospital clinics when they come for a follow-up appointment. The coach calls them
      in between face-to-face visits to go over their treatment plan and answer any
      questions. Program lasts for 30 days after patient is discharged.

PMID- 21942154
TI  - Hospitals, SNFs team up to improve transitions.
AB  - Summa Health System and Akron, OH, area nursing homes are working together to
      improve patient transitions and quality of care. Readmissions have dropped from,
      26% to 19% and length of stay has dropped from 7.3 days to a low of 7 days.
      Multidisciplinary teams meet regularly to discuss better ways of handing off
      patients. The team developed a standardized transfer form that hospitals use when
      transferring patients. Nursing facilities started using the Situation-Background
      Assessment-Recommendation (SBAR) form to organize information for physicians when
      patients have a change in condition.

PMID- 21942155
TI  - Education and follow-up cut HF readmissions.
AB  - A heart failure pilot project at Indiana University Health Ball Memorial Hospital
      in Muncie cut the readmission rate by 50%. Patients receive intensive coaching
      while in the hospital, and they receive weekly follow-up calls after discha rge.
      Team members use the teach-back method to ensure patients understand their
      treatment plan. They teach patients to use the Heart Failure Zones to determine
      what to do if their conditions change.

PMID- 21942156
TI  - Factors related to physical activity and recommended intervention strategies as
      told by midlife and older African American men.
AB  - OBJECTIVE: Few interventions have targeted preventive health behaviors of midlife
      and older African American (AA) men. This study derived pertinent information
      with personal interviews to develop a tailored physical activity (PA)
      intervention for AA men -45 years of age. METHODS: Participants were 49 AA men
      aged 45-88 years. Personal interviews ascertained PA barriers, enablers, and
      preferences, and components that would render a PA program appropriate for and
      appealing to AA men of similar ages. Taped interviews were transcribed and
      organized in NVivo for analysis. Common themes were identified by multiple
      research staff. RESULTS: Most often cited barriers to PA included time
      constraints, lack of social support, low motivation, poor access, and factors
      related to chronic conditions and aging. Although men preferred traditional forms
      of sports and exercise when younger, they learned to adapt the intensity and
      duration as they aged, and walking was viewed as an acceptable alternative.
      Recommended strategies for a community-based PA program were building social
      support, camaraderie, and accountability among men through healthy/friendly
      competition and social interaction, using accessible community facilities, and
      including education about men's and aging-related health issues. CONCLUSION: The
      qualitative research process yielded new and insightful information that can be
      used to develop a tailored PA and health program for midlife and older AA men.

PMID- 21942157
TI  - Attitudes of African American advocates toward childhood obesity.
AB  - OBJECTIVE: To report the childhood obesity-related attitudes and beliefs of
      community advocates who are serving African-American children. METHODS: Attendees
      at the 2009 National Black Child Development Institute (NBCDI) annual meeting who
      also attended the session on childhood obesity were surveyed. Surveys were self
      administered prior to the start of the session. RESULTS: Survey respondents felt
      that social determinants like heavy advertising, high cost of healthful food, etc
      were contributors to the childhood obesity epidemic while simultaneously
      believing that parents were ultimately responsible for shaping their children's
      eating behaviors. CONCLUSIONS AND IMPLICATIONS: African American children are
      plagued by a number of different risk factors. The job of advocates is very
      important in addressing these problems, however, advocates often find it
      difficult to split their time between each area. Health care professionals might
      be better served by developing disease risk reduction comprehensive programs when
      working with these communities.

PMID- 21942158
TI  - Yo-yo dieting in African American women: weight cycling and health.
AB  - OBJECTIVE: Research on the effects of weight cycling on health is mixed, strife
      with inconsistent definitions and the exclusion of African Americans. This study
      examined weight cycling prevalence among African American women prior to
      enrolling in a weight management program. Associations of weight cycling with
      physical and psychological health were conducted. DESIGN: Cross-sectional
      analysis. SETTING: Community-based weight-management program. PARTICIPANTS: 167
      overweight or obese treatment-seeking African American women. MAIN OUTCOME
      MEASURES: Weight cycling was examined in relation to physiological factors,
      including eating pathology, mood, self esteem, and physical health, specifically
      current weight, ideal weight, peak weight, and blood pressure. RESULTS: Weight
      cycling was prevalent (63%). Cyclers had higher current and peak weights (P<.01).
      Blood pressure did not differ between groups. Cyclers had higher drive for
      thinness, less body satisfaction, and less self-esteem for appearance (P<.05).
      CONCLUSION: African American women are at risk for weight cycling and it may be
      associated with greater weight and poorer measures of psychological health.

PMID- 21942159
TI  - Body image and physical activity among Latina and African American women.
AB  - OBJECTIVES: Obesity in African American (AA) and Hispanic or Latina (HL) women
      has been partly attributed to low physical activity (PA) and cultural influences
      on body image. The purpose of this study was to determine the relationship among
      body mass index (BMl=kg/m2), body image perception (perceived and desired) and
      PA. DESIGN: The current study is a cross-sectional, secondary data analysis of
      the Health Is Power (HIP) project (1R01CA109403). SETTING: Women residing in
      Harris County, Houston and Travis County, Austin, Texas were recruited to
      participate in the study. PARTICIPANTS: Over four hundred (N=410) AA (N=262) and
      HL (N=148) women participated in the HIP project and were included in the current
      study. MAIN OUTCOME MEASURES: BMI, Pulvers' body image, PA and demographic data
      were collected from each participant. RESULTS: Women (mean age=45.2 yrs) were
      educated (44% college graduates) and obese (mean BMI =34.6 kg/m2). Less than half
      perceived themselves correctly regardless of actual weight and ethnicity
      (P<.001). Nearly three-fourths of AA (73.9%) and less than half of HL (42.9%)
      women who were normal weight desired to be obese, and only 39.4% of AA and HL
      women desired to be normal weight. Women varied on measures of PA (P<.05).
      Regression analyses showed objectively measured PA was significantly associated
      with BMI and ethnicity (P<.01). CONCLUSIONS: Results reveal dichotomous
      distortion in body images. Women need strategies to perceive normal weight as
      desirable for health and beauty, leading to increased PA and reducing obesity.

PMID- 21942160
TI  - Development of a new body image assessment scale in urban Cameroon: an
      anthropological approach.
AB  - OBJECTIVE: Develop and validate body image scales (BIS) presenting real human
      bodies adapted to the macroscopic phenotype of urban Cameroonian populations.
      DESIGN: Quantitative and qualitative analysis. SETTING: Yaounde, capital city of
      Cameroon. PARTICIPANTS: Four samples with balanced sex-ratio: the first (n=16)
      aged 18 to 65 years (qualitative study), the second (n=30) aged 25 to 40 years
      (photo database), the third (n=47) and fourth (n=181), > or =18 years (validation
      study). MAIN OUTCOME MEASURE: Construct validity, test retest reliability,
      concurrent and convergent validity of BIS. RESULTS: Body image scales present six
      Cameroonians of each sex arranged according to main body mass index (BMI)
      categories: underweight (<18.5 kg/m2), normal (18.5-24.9 kg/m2), overweight (25
      29.9 kg/m2), obesity class I (30-34.9 kg/m2), obesity class II (35-39.9 kg/m2),
      and obesity class III (> or =40 kg/m2). Test-retest reliability correlations for
      current body size (CBS), desired body size and current desirable discrepancy
      (body self-satisfaction index) on BIS were never below .90. Plus, for the
      concurrent validity, we observed a significant correlation (r=0.67, P<.01)
      between measured BMI and CBS. Finally, the convergent validity between BIS and a
      female African American silhouettes scale, for different dimensions of body size
      perceptions, is acceptable. CONCLUSIONS: Body image scales are adapted to the
      phenotypic characteristics of urban Cameroonian populations. They are reliable
      and valid to assess body size perceptions and culturally adapted to the
      Cameroonian context.

PMID- 21942161
TI  - Acute myocardial infarction quality of care: the Strong Heart Study.
AB  - OBJECTIVES: Evaluate the quality of care provided patients with acute myocardial
      infarction and compare with similar national and regional data. DESIGN: Case
      series. SETTING: The Strong Heart Study has extensive population-based data
      related to cardiovascular events among American Indians living in three rural
      regions of the United States. PARTICIPANTS: Acute myocardial infarction cases
      (72) occurring between 1/1/2001 and 12/31/2006 were identified from a cohort of
      4549 participants. OUTCOME MEASURES: The proportion of cases that were provided
      standard quality of care therapy, as defined by the Healthcare Financing
      Administration and other national organizations. RESULTS: The provision of
      quality services, such as administration of aspirin on admission and at
      discharge, reperfusion therapy within 24 hours, prescription of beta blocker
      medication at discharge, and smoking cessation counseling were found to be 94%,
      91%, 92%, 86% and 71%, respectively. The unadjusted, 30 day mortality rate was
      17%. CONCLUSION: Despite considerable challenges posed by geographic isolation
      and small facilities, process measures of the quality of acute myocardial
      infarction care for participants in this American Indian cohort were comparable
      to that reported for Medicare beneficiaries nationally and within the resident
      states of this cohort.

PMID- 21942162
TI  - Prevalence of metabolic syndrome in the indigenous population, aged 19 to 69
      years, from Jaguapiru Village, Dourados (MS), Brazil.
AB  - OBJECTIVE: To evaluate the prevalence of metabolic syndrome in an indigenous
      Brazilian population. METHODS: Indigenous Brazilians aged 18-69 years from
      Jaguapiru Village, Dourados, MS were studied. Participants were selected by
      simple random sampling of 360 houses in the village. The abdominal circumference
      of the population was evaluated, and measurements <80 cm for females or <90 cm
      for males were considered normal. Capillary blood glucose levels by glucometer
      and oral glucose tolerance tests were measured, and, when necessary, total
      cholesterol, HDL cholesterol and triglyceride levels were assessed. RESULTS: Of
      the 632 indigenous Brazilians in the study, 281 were males. We observed that 287
      (45.4%) presented abdominal circumference values greater than normal; of those,
      199 were women (43.4% of all women in the study) and 88 were men (26.1% of all
      men in the study). CONCLUSION: Metabolic syndrome is common in the Indian
      Jaguapiru Village.

PMID- 21942163
TI  - Racial and rural-urban disparities in stroke mortality outside the Stroke Belt.
AB  - OBJECTIVES: Stroke disparities in relation to the Stroke Belt have been studied
      extensively, but little is known about stroke mortality disparities outside the
      Stroke Belt. We examined the hypothesis that racial and rural-urban stroke
      disparities exist outside the Stroke Belt. DESIGN, SETTING, PARTICIPANTS: A
      county-based population study of stroke mortality in adults, aged -25 years, for
      a seven-year period (2000-2006) was conducted in the non-Stroke Belt states. Data
      on stroke deaths were obtained from the Centers for Disease Control and
      Prevention, National Center for Health Statistics. Relative risks (RR) were
      estimated by multivariable Poisson regression, adjusting for known confounders.
      MAIN OUTCOME MEASURE: Stroke death rates. RESULTS: In the non-Stroke Belt states,
      African Americans had 1.44 times higher stroke death rates than Caucasians, 2.14
      times higher than Asians/Pacific Islanders, and 1.56 times higher than American
      Indians (adjusted RR=1.44, P<.001; adjusted RR=2.14, P<.001; and, adjusted
      RR=1.56, P<.001, respectively). After adjusting for race, sex, and age, residents
      of rural counties outside the Stroke Belt still had a statistically significant
      12% increase in stroke mortality compared to urban counties (adjusted RR=1.12,
      P<.001). Female sex and older age were also associated with higher stroke
      mortality. CONCLUSIONS: The present study revealed that racial and rural-urban
      disparities in stroke mortality exist in populations residing outside the Stroke
      Belt. Stroke mortality in the non-Stroke Belt states is disproportionately higher
      in African Americans and in rural area residents. African Americans are the only
      racial group in which urban residency is not associated with a decrease in stroke
      mortality.

PMID- 21942164
TI  - Acculturation, coronary artery disease and carotid intima media thickness in
      South Asian immigrants--unique population with increased risk.
AB  - CONTEXT: South Asian Immigrants (SAls) are the 2nd fastest growing Asian
      immigrant population in the United States with high rates of coronary artery
      disease (CAD) and type 2 diabetes (T2D). There is a need to identify markers that
      can help in identifying high risk groups at an early stage so CAD can be
      prevented. OBJECTIVE: To measure the level of acculturation and its association
      with CAD, sub-clinical CAD, CAD risk factors and T2D in SAls in the United
      States. DESIGN: Using an epidemiologic cross-sectional study design, 159 SAls
      aged 35-65 years were recruited. Subclinical CAD was assessed using common
      carotid artery intima media thickness (CCA-IMT) as a surrogate marker for
      atherosclerosis. Scaled (The Suinn-Lew Asian Self-Identity Acculturation scale
      [SL-ASIA Scale]) and non-scaled (> or =10 years stay in the United States)
      methods were used to measure the acculturation. RESULTS: 67.7% of SAls were
      identified to have high acculturation based on SL-ASIA scale. On the logistic
      regression age-adjusted model, > or =10 years stay in the US (P=.006),
      cholesterol level > or =200 mg/dL (P<.001), BMI> or =-2 (P=.004), and family
      history of CAD (.007) were found to be significantly associated with CAD. T2D was
      associated with high acculturation (P<.001) and CCA-IMT (P=.01) beside other CAD
      risk factors. CONCLUSIONS: Acculturation may play a major role in predisposing
      immigrant populations to CAD, however insufficient research has been done in this
      field. Further studies are needed to provide large scale information on
      acculturations and its association with CAD.

PMID- 21942165
TI  - The relative impact of diabetes distress vs depression on glycemic control in
      hispanic patients following a diabetes self-management education intervention.
AB  - OBJECTIVES: Studies in non-Hispanic populations have shown that depression and
      diabetes distress are associated with glycemic control. Although rates of
      depression and diabetes distress are high among Hispanics with diabetes, there is
      little research investigating the relationship between these factors and glycemic
      control in this population. The purpose of the current analysis was to examine
      the relative impact of change in diabetes distress and change in depressive
      symptoms on change in glycemic control in Hispanic patients following a diabetes
      self-management education (DSME) intervention. DESIGN: We conducted a diabetes
      self-management education intervention in 23 Hispanic (predominantly Puerto
      Rican) and 168 non-Hispanic type 2 diabetes patients and measured glycemic
      control (HbA1c), depressive symptoms (CES-D), and diabetes distress (PAID) at
      baseline and 6 months. RESULTS: In multiple linear regression, change in diabetes
      distress from baseline to six-month follow-up was significantly associated with
      change in HbA1c among Hispanic patients, such that a 10-point reduction on the
      PAID scale of diabetes distress was associated with a clinically significant
      reduction in HbA1c of .55 +/- .06% (P=.03). Change in depression was not
      associated with change in HbA1c (P=.59). Findings in non-Hispanic patients were
      similar. CONCLUSIONS: Change in diabetes distress, but not change in depressive
      symptoms, was associated with change in HbA1c in both Hispanic and non-Hispanic
      patients. This analysis supports the utility of DSME in reducing diabetes
      distress and improving glycemic control among Hispanic patients.

PMID- 21942166
TI  - Food insecurity is related to increased risk of type 2 diabetes among Latinas.
AB  - OBJECTIVES: To examine the independent association of food insecurity with type 2
      diabetes (T2D), and to identify the T2D risk factors related to food insecurity
      among Latinas. METHODS: Case-control study in a convenience sample of 201 Latinas
      (100 cases with T2D, 101 controls) aged 35-60 years and living in an urban
      setting. Self-reported data, including food insecurity, T2D status, depression
      symptoms, and socioeconomic, demographic, and lifestyle characteristics (food and
      alcohol intake, cigarette smoking, physical activity) were collected, and height,
      weight and waist circumference were measured. Separate multivariate logistic
      regression models were specified for T2D and food insecurity. RESULTS:
      Participants with very low food security were 3.3 times more likely to have T2D
      (OR 3.33, 95% CI 1.34-8.23) independently of employment status, acculturation,
      waist circumference, and lifestyle characteristics. High waist circumference
      (>88cm) (OR 2.46, 95% CI 1.13-5.38) and being in the lowest quartile of physical
      activity level (OR 3.75, 95% CI 1.21-11.62) were also risk factors for T2D.
      Elevated depression symptoms and participation in the Supplemental Nutrition
      Assistance Program (SNAP) were positively related to low and very low food
      security after adjusting for waist circumference (P<.01); cigarette smoking was
      positively associated with very low food security, and nutrition knowledge was
      negatively related to low food security (P<.01). CONCLUSIONS: These results
      highlight the need for interventions focusing on prevention of depression and
      food insecurity among Latinas with T2D.

PMID- 21942167
TI  - African American parents' attitudes toward HPV vaccination.
AB  - This study sought to determine knowledge about human papillomaviruses (HPV),
      vaccination acceptability and intent to vaccinate, and describe the individual
      characteristics, and sociocultural attitudes that affect African American
      parents' intent to vaccinate their daughters. Two hundred African Americans
      completed self-administered surveys that assessed factors that may influence HPV
      vaccination behavior, HPV and cervical cancer knowledge and risk perception,
      cultural attitudes, and preferences for location and timing of vaccination.
      Eligibility criteria included men and women who had a daughter aged 9 to 17
      years, whether the daughter had or had not been told that she had an HPV
      infection. Approximately two-thirds of the African American parents surveyed were
      aware of HPV and HPV vaccination. Responders were likely to be female, younger,
      employed, and to have social resources. They were also knowledgeable about HPV,
      but knowledge did not necessarily lead to vaccination. Among parents
      knowledgeable about HPV, vaccination status was significantly affected by whether
      a pediatrician had recommended the vaccine. There were no significant differences
      in demographic characteristics or sociocultural attitudes between the parents who
      had vaccinated their daughters and those who had not, although more of the
      parents who had vaccinated daughters were worried about STIs.

PMID- 21942168
TI  - Culture and colorectal cancer screening on three American Indian reservations.
AB  - BACKGROUND: Colorectal cancer (CRC) rates among many American Indian populations
      are high. Screening by fecal occult blood test (FOBT) and endoscopy is effective
      for reducing CRC mortality, but little research has examined the extent of such
      screening in reservation populations. Further, nothing is known of how American
      Indians' cultural characteristics may be related to screening receipt.
      PARTICIPANTS AND SETTING: We examined data from participants recruited from 2
      Northern Plains and 1 Southwest reservation for the Education and Research Toward
      Health (EARTH) study. All participants aged > or = 51 years were eligible for
      inclusion. DESIGN: After calculating screening rates, we examined bivariate
      relationships between screening and participant characteristics, including
      measures of cultural characteristics including ethnic identity and use of
      traditional healing practices. We applied multivariate regression to relate these
      cultural variables to odds of lifetime screening by FOBT or endoscopy. RESULTS:
      Of 751 American Indians sampled, 35% reported lifetime CRC screening by at least
      one modality. Multivariate analyses did not reveal significant relationships or
      trends relating FOBT to respondents' cultural characteristics. By contrast, odds
      of endoscopy were significantly lower among persons who spoke a tribal language
      at home (OR .6, 95% C.I. .4-.9), and trend analysis revealed an inverse
      relationship between endoscopy and number of identity measures endorsed
      (Ptrend<.1). CONCLUSIONS: The sampled population exhibits disparities in CRC
      compared to the general population, and cultural characteristics are related to
      odds of endoscopy. Findings warrant culturally tailored CRC screening initiatives
      for American Indians.

PMID- 21942169
TI  - The effects of Obama's political success on the self-rated health of blacks,
      Hispanics, and whites.
AB  - Stress in the social environment can affect individual health. Election of the
      first Black President of the United States provides an opportunity to assess how
      a positive change in the macro-political climate impacts the health of Americans.
      Past research suggests that race-related political events influence the health of
      non-dominant racial groups. Yet many questions remain, including the types of
      events that affect health, the timing and durability of health effects, and
      whether effects are similar for Blacks and Hispanics in the United States. The
      present study uses data from the Ohio Family Health Survey, which was in the
      field from August 6, 2008 until January 24, 2009, to assess whether immediate
      changes in average self-rated health occurred after key events in the election of
      President Barack Obama. We find better average health ratings among Blacks and
      Hispanics immediately following Obama's nomination by the Democratic Party.
      Similar effects did not occur after the election or inauguration, and Whites
      showed no effect of any of the events. We discuss the implications of these
      findings in terms of the theoretical links between macro-level social conditions,
      race/ethnicity, and health.

PMID- 21942170
TI  - Increased patient delays in care after the closure of Martin Luther King
      Hospital: implications for monitoring health system changes.
AB  - BACKGROUND: The safety net system remains an important part of the health care
      system for uninsured and minority populations, however, the closure of safety net
      hospitals changes the availability of care. Using community-based participatory
      research methods, we explored the impact of hospital closure among late middle
      aged and elderly racial/ethnic minorities in South Los Angeles. METHODS:
      Telephone survey of participants in both 2008, after hospital closure, and 2003,
      before hospital closure, who self-identified as African American or Latino, were
      over the age of 50 and lived in zip codes of South Los Angeles. We developed
      multiple logistic regression models on imputed data sets weighted for non
      response and adjusted for self-reported measures of demographic and clinical
      characteristics to examine the odds of reporting delays in care. RESULTS: After
      adjusting for covariates known to influence access to care and distributed
      differently in the two survey samples, we found significantly greater delays in
      care. Following the closure of the Martin Luther King, Jr. safety net hospital,
      the adjusted odds ratios were 1.70 (95% CI 1.01, 2.87) for delays in care, 1.88
      (95% Cl 1.06, 3.13) for problems receiving needed medical care, and 2.62 (95% CI
      1.46, 4.67) for seeing a specialist. CONCLUSIONS: Our survey of older minority
      adults in South Los Angeles found increased delays in access to care for needed
      medical services after the closure of Martin Luther King, Jr. Hospital. As health
      care reform unfolds, monitoring for changes in access to care that may result
      from new policies will be important to address future disparities, particularly
      for vulnerable populations.

PMID- 21942171
TI  - The impact of thalassemia on Southeast Asian and Asian Indian families in the
      United States: a qualitative study.
AB  - OBJECTIVE: To describe the challenges, including sociocultural and socioeconomic
      barriers, faced by an urban immigrant population in the United States affected by
      thalassemia major. DESIGN: Ethnographic, semi-structured, 1-on-1 interviews using
      an interview guide developed for this study. Digital recordings were transcribed
      and data analyzed using constant comparative method. SETTING: University-based,
      Comprehensive Thalassemia Program at Children's Memorial Hospital, Chicago, IL,
      USA. PARTICIPANTS: Fourteen Southeast Asian and Asian Indian parents of children
      with transfusion dependent thalassemia. MAIN OUTCOME MEASURE: Qualitative
      descriptions of parental experiences, frequency of codes applied to interviews
      and emergent themes. RESULTS: Thalassemia has its greatest impact on the
      emotional and social well-being of affected children and their parents. Current
      and future concerns were related to disease-specific complications and challenges
      with management such as transfusions and chelation therapy. These perceptions
      were tied to parental hope for a cure, a frequently coded coping mechanism.
      Despite their availability, few parents relied on support systems beyond
      immediate family members due to perceived public knowledge gaps about
      thalassemia. Culturally based past experiences and barriers did not emerge as
      dominant themes in our analysis. CONCLUSION: The impact of thalassemia is
      tremendous for affected children and their parents and is due more to factors
      that were either disease-specific or common to other chronic disease models
      rather than those influenced by culture. The unmet needs of these families
      require additional investigation to facilitate the development of initiatives
      aimed at improving quality of life and lessening overall impact of thalassemia

PMID- 21942172
TI  - African American women's exposure to interpersonal racial discrimination in
      public settings and preterm birth: the effect of coping behaviors.
AB  - OBJECTIVES: To determine whether African American women's coping behaviors modify
      the relationship between exposure to interpersonal racial discrimination in
      public settings and preterm birth (<37 weeks). DESIGN: A case-control study was
      performed among African American women delivering infants at two tertiary care
      hospitals in Chicago, IL between July 2001-June 2005. A structured questionnaire
      was administered to measure maternal perceived exposure to interpersonal racial
      discrimination in public settings and coping behaviors. RESULTS: A greater
      percentage of African American mothers of preterm infants had high lifetime and
      past year exposure to racism in public settings than their peers who deliver term
      infants; odds ratios (OR) and 95% confidence intervals (95% CI) equaled 1.5 (0.9
      2.8) for lifetime and 2.5 (1.2-5.2) for past year exposure. Active coping,
      especially "working harder to prove them wrong" led to attenuated ORs
      (interaction P value<.05 for lifetime and <.10 for past year. CONCLUSIONS:
      African American women's exposure to racism in public settings is a risk factor
      for preterm birth; active coping behaviors weaken this relationship.

PMID- 21942173
TI  - Health-related quality of life among African Americans with multiple sclerosis.
AB  - OBJECTIVE: Identify factors associated with health-related quality of life
      (HRQOL) among African Americans with multiple sclerosis (MS). DESIGN: A survey
      cohort was recruited from the Registry of the North American Research Committee
      On Multiple Sclerosis (NARCOMS) Project. Data were collected from 131 African
      Americans with MS, with 111 participants providing all data needed for analyses
      of physical domains and 103 participants providing all data needed for analyses
      of mental health domains of HRQOL using multiple linear regression models.
      RESULTS: Worsening MS symptoms and greater interference of MS symptoms with daily
      life were associated with significantly lower physical domains of HRQOL.
      Respondents reporting that their principal care physician who had a greater
      understanding of how MS symptoms affected their daily lives tended to have
      significantly higher physical dimensions of HRQOL. A previous diagnosis of
      depression and agreement that participants were sometimes embarrassed in public
      due to their MS were associated with significantly lower mental health aspects of
      HRQOL. CONCLUSION: Findings highlight the importance of the positive association
      between the level of understanding by the principal care physician of how MS
      symptoms affect the lives of African Americans and their physical dimensions of
      HRQOL. Physicians treating African Americans with MS need to understand how MS
      symptoms impact the life of these patients as a key component to providing
      culturally competent care.

PMID- 21942174
TI  - [Effect of moxibustion on colonic TNF-alpha content and influence of colonic
      supernatant of crohn's disease rats undergoing moxibustion on expression of
      occludin, claudin-1 and zonula occludens-1 proteins and genes in cultured colonic
      epithelial cells].
AB  - OBJECTIVE: To observe the effect of moxibustion on colonic tumor necrosis factor
      (TNF)-alpha level in Crohn's Disease (CD) rats and the effect of colonic
      supernatant of CD rats experiencing moxibustion on the expression of the tight
      junction proteins ocoludin, claudin-1 and zonula occiludens (ZO)-1 and their
      genes in the cultivated colonic epithelial cells derived from CD rats, so as to
      reveal its underlying mechanism in resisting colonic epithelial barrier defects.
      METHODS: Sixty SD rats were randomized into normal control, model, moderately
      warm moxibustion (MWM), herbs-partitioned moxibustion (HPM) and medication
      (salazosulfapyridine, SASP) groups (n=12). CD model was established by intra
      annual perfusion of trinitrobenzene sulfonic acid (TNBS) solution (TNBS: 50%
      alcohol = 2:1, 0.5 mL/kg). For rats of the HPM and MWM groups, moxibustion was
      given to "Tianshu" (ST 25) and "Qihai" (CV 6) once daily for 14 d. For rats of
      the medication group, intragastric perfusion of SASP solution (0. 0405 g/3 mL)
      was given twice daily for 14 d. After the treatment, all the rats including those
      of normal group were killed for preparing the supernatant of colonic mucosa
      tissue (6-8 cm superior to the anus). The colonic epithelial cells of the normal
      group were purified and cultivated in DMEM culture fluid containing the prepared
      supernatant of normal group to establish an intestinal epi-thelial barrier defect
      model, and also cultured separately in the media containing the prepared
      supernatants of the model, medication, HPM and MWM groups. One week after the
      culture, the expression levels of occludin, claudin-1 and ZO-1 proteins and their
      genes in the cultured colonic epithelial cells were detected by Western blot and
      fluorescent quantitative polymerase chain reaction assay respectively. TNF-a
      content of the colonic supernatant was detected by enzyme linked immunosorbent
      assay. RESULTS: Compared with the normal group, colonic TNF-alpha content was
      remarkably increased in the model group (P < 0.01). In comparison with the model
      group, colonic TNF-acx contents were significantly decreased in the medication,
      MWM and HPM groups (P < 0.01), and those of the MWM and HPM groups were markedly
      lower than that of the medication group (P < 0.05). The expression levels of the
      cultured normal colonic epithelial occludin, claudin-1 and ZO-1 proteins and
      their mRNAs in the medication, MWM and HPM groups were remarkably increased
      compared with those in the model group (P < 0.01, P < 0.05). The expression
      levels of colo-nic epithelial occludin, claudin-1 and ZO-1 proteins and their
      mRNAs were significantly higher in the MWM and HPM groups than in the medication
      group (P < 0.05). CONCLUSION: Both MWM and HPM can downregulate colonic mucosal
      TNF-alpha content in CD rats, and the colonic supernatant of rats undergoing MWM
      and HPM may upregulate the expression of colonic epithelial occludin, claudin-1
      and ZO-1 proteins and their mRNAs in the cultivated colonic epithelial cells,
      which may contribute to the effect of moxibustion in relieving colonic epithelial
      barrier defect.

PMID- 21942175
TI  - [Effect of penetrative needling of scalp-acupoints on cerebral N-acetyl-aspartate
      and choline levels in intracerebral hemorrhage rabbits].
AB  - OBJECTIVE: To observe the effect of scalp-acupuncture on N-acetyl-aspartate (NAA)
      and choline (Cho) leveIs in the brain tissue in rabbits with intracerebral
      hemorrhage (ICH) so as to explore its underlying mechanisms in resisting neural
      lesion. METHODS: A total of 30 Newzealand rabbits were randomly divided into
      normal, model and acupuncture groups (n=10). ICH model was duplicated by
      injection of the rabbit-own blood (200 microL) into the bilateral Basal Nuclei
      (A: 2 mm; R, L; 5 mm; H: 10 mm). A filiform needle was inserted into "Baihui" (GV
      20) to "Taiyang" (EX-HN 5) on the hemorrhage side, manipulated for 1 min, and
      then retained for 30 min (manipulated once again every 10 min). The treatment was
      conducted once daily for 7 days. Contents of NAA, Cho and creatine (Cr) in the
      intracerebral peri-hematoma tissues were detected by using 1H-Magnetic Resonance
      Spectroscopy (MRS). RESULTS: Compared with the normal group, NAA/Cr ratios at the
      time points of 2 h, 3 d and 7 d after ICH in the model group were decreased
      markedly (P < 0.05), while Cho/Cr ratios at the same 3 time-points after ICH in
      the model group were increased markedly (P < 0.05). In comparison with the model
      group, NAA/Cr ratio on day 3 after ICH in the acupuncture group was obviously
      higher (P < 0.05), while Cho/Cr ratios on day 3 and 7 were significantly down
      regulated in the acupuncture group (P < 0.05). No significant changes were found
      in NAA/Cr ratios at 2 h and on day 7 and in Cho/Cr ratio at 2 h after ICH between
      the acupuncture group and the model group. CONCLUSION: Penetrative acupuncture of
      GV 20-EX-HN 5 is effective in suppressing ICH-induced increase of Cho/Cr ratio in
      ICH rabbits, which may contribute to its function in accelerating neural repair
      process.

PMID- 21942176
TI  - [Effect of acupoint-injection of stem cell factor antibody on electroacupuncture
      induced changes of count and degranulation of subcutaneous mast cells in the
      local region in rats].
AB  - OBJECTIVE: To observe the alternations of local mast cells (MCs) in the number
      and functional activities after electroacupuncture (EA) and injection of stem
      cell factor (SOF) antibody into "Weishu" (BL 21) and "Zusanli" (ST 36) in rats.
      METHODS: Thirty Wistar rats were randomly assigned to normal, EA, and EA + SCF
      antibody injection (EA-ABI) groups (n=10). EA was applied to the left "Weishu"(BL
      21) and "Zusanli" (ST 36) for 25 min. For rats of EA+ ABI group, SOF-AB (1:200,
      0.1 mL) was respectively injected into BL 21 and ST 36, following by EA. The
      tissues around the two acupoints areas were sampled to be stained with
      acetylcholine esterase (AchE) and toluidine blue (TB), respectively. The counts
      and degranulation ratio of MOs in the acupoint region were recorded and observed
      under microscope. RESULTS: In comparison with the normal group, MCs count was
      increased significantly in the EA of "Weishu" (BL 21) group (P < 0.05), mildly in
      the EA of "Zusanli" (ST 36) group (P > 0.05), and downregulated considerably in
      both EA-ABI-BL 21 and EA-ABI-ST 36 groups (P < 0.05) . Compared with the normal
      group, the degranulation ratio of MCs was increased significantly in EA-BL 21, EA
      ST 36, EA-ABI-BL 21 and EA-ABI-ST 36 groups (P < 0.5). No significant differences
      were found between EA-BL 21 and EA-ABI-BL 21 groups, and between EA-ST 36 and EA
      ABI-ST 36 groups in the degranulation ratios (P > 0.05). CONCLUSION: Local
      injection of SCF antibody in BL 21 and ST 36 can significantly suppress EA
      induced increase of the number and degranulation ratio of local subcutaneous MCs
      in rats, suggesting that SCF is an important factor affecting the activity and
      recruitment of MCs around the acupoint during EA.

PMID- 21942177
TI  - [Effects of acupuncture on expression of norepinephrine transporter mRNA in the
      cervical sympathetic ganglion and beta1-AR mRNA in the heart in cerebral-cardiac
      syndrome rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) intervention on the
      expression of norepinephrine transporter (NET) mRNA in the middle cervical
      stellate ganglion complex (MC-SGC) and beta1-adrenergic receptor (beta1-AR) mRNA
      in the left ventricular myocardium in cerebral-cardiac syndrome (CCS) rats, so as
      to study its underlying mechanism in the prevention and treatment of CCS.
      METHODS: Eighteen Wistar rats were randomized into sham operation, model and EA
      groups (n=6). CCS model was duplicated by intravenous injection of 1 microL of
      saline containing collagenase (1 U/microL) + heparin (7 U/microL) into the
      caudate nucleus. EA (2 Hz, 5 V) was applied to "Shuigou" (GV 26)-"Fengfu" (GV
      16), and "Neiguan" (PC 6)-"Xinshu" (BL 15) for 20 min, once daily for 3 days.
      Seventy-two hours after modeling, pathological changes of the brain and cardiac
      tissues were observed after sectioning and stained with HE method. The expression
      of MC-SGC NET mRNA and the myocardial p1-AR mRNA of the left ventricle were
      detected by fluorescence quantitative PCR. RESULTS: (1) In comparison with the
      model group, the number of the exuded red blood cells in the brain tissue around
      the caudate Nucleus region was fewer, the severity of the tissue edema, cell
      necrosis, and inflammatory cell infiltration lighter in the EA group. Compared
      with the model group, the severity of degeneration and necrosis of myocytes was
      lighter and the number of the broken cardiac smooth muscle fewer in the EA group.
      (2) The expression levels of both MC-SGC NET mRNA and myocardial beta1-AR mRNA
      were significantly lower in the model group than in the sham operation group (P <
      0.01). Compared with the model group, the expression levels of both MC-SGC NET
      mRNA and myocardial beta1-AR mRNA were upregulated considerably in the EA group
      (P < 0.01). CONCLUSION: EA of GV 26-GV 16 and PC 6-BL 15 can upregulate the
      expression of both MC-SGC NET mRNA and myocardial beta1-AR mRNA in CCS rats which
      may contribute to its effect in the prevention and treatment of CCS syndrome.

PMID- 21942178
TI  - [Effect of moxibustion on quantity of pinealocytes and pineal HSP 70 expression
      in subacute aging rats].
AB  - OBJECTIVE: To study the mechanism of moxibustion in postponing the process of
      aging. METHODS: Thirty Wistar rats were equally randomized into control, model
      and moxibustion groups. The subacute aging model was established by hypodermic
      injection of 25% D-galactose (125 mg/kg). Moxibustion was applied to bilateral
      "Shenshu" (GV 23) and "Pishu" (GV 20) once everyday for 6 weeks. After slicing,
      the pineal gland tissue was stained with HE and insitu hybridization methods
      respectively for detecting the quantity of pinealocytes and the expression of
      heat shock protein (HSP 70). RESULTS: Compared with the control group, both the
      quantity of pinealocytes and the expression of HSP 70 in the pineal gland in the
      model group were downregulated significantly (P < 0.001, P < 0.01). Compared with
      model group, the quantity of pinealocytes and of HSP 70 mRNA in the pineal gland
      of moxibustion group were upregulated significantly (P < 0.01, P < 0.05).
      CONCLUSION: Moxibustion can suppress aging induced decrease of pinealocyte number
      and HSP 70 expression in subacute aging rats, which may contribute to its effect
      in postponing aging.

PMID- 21942179
TI  - [Neuroanatomical basis of clinical joint application of "Jinggu" (BL 64, a source
      acupoint) and "Dazhong" (KI 4, a Luo-acupoint) in the rat: a double-labeling
      study of cholera toxin subunit B conjugated with Alexa Fluor 488 and 594].
AB  - OBJECTIVE: To study the specific correlation between "Jinggu" (BL 64) and
      "Dazhong" (KI 4) in the nervous system by using a double-labeling of cholera
      toxin subunit B conjugated with Alexa Fluor 488 and 594 (CTB-Alexa 488, 594) in
      rats, so as to investigate its neuroanatomical basis for clinical joint
      application of Yuan-Source and Luo acupoints. METHODS: Three male SD rats were
      used in the present study. Under anesthesia (10% urethane), 0.1% CTB-Alexa 488 (5
      microL) and CTB-Alexa 594 (5 microL) were respectively injected into the border
      area between the red and white flesh, distal to the tuberosity of the fifth
      metatarsal bone, and the depression anterior to the medial attachment of the
      calcaneal tendon, the corresponding sites of the acupoints Jinggu (BL 64) and
      Dazhong (KI 4) in the human body. After 3 surviving days, the rat's brain, spinal
      cord and dorsal root ganglia (DRGs) of L3-L6 were dissected following perfusion
      with 4% paraformaldehyde, cut into sections and observed under fluorescent
      microscope equipped with a digital camera. The labeled neurons were recorded and
      counted. RESULTS: It was found under fluorescent microscope that the single
      labeled neurons and the dual-labeled neurons were ipsilaterally located on the
      injected side. Among the single-labeled neurons, the labeled sensory neurons
      related to "Jinggu" (BL 64) and "Dazhong" (KI 4) were found to be in the DRGs of
      L3-L6, with a higher concentration in the DRGs of L.4 (27/162, 102/332) and L5
      (130/162, 204/332). The dual-labeled 7 neurons were found to be in DRGs of L4 and
      L5. In addition, the labeled motoneurons related to "Jinggu" (BL 64) and
      "Dazhong" (KI 4) distributed in the dorsolateral portion of lamina IX, forming a
      longitudianal column from L3-L6 with a higher concentration at L4 and L5.
      CONCLUSION: The labeled sensory and motor neurons innervating Yuan-acupoint
      "Jinggu" (BL 64) and Luo-acupoint "Dazhong" (KI 4) distribute in DRGs of the same
      spinal segments and spinal ventral horns from L3-L6.

PMID- 21942180
TI  - [Effect of acupuncture of "Zusanli"(ST 36)on sexual hormone levels in spleen
      deficiency syndrome rats].
AB  - OBJECTIVE: To study the underlying mechanism of acupuncture of "Zusanli" (ST 36)
      in clinical treatment of spleen deficiency syndrome (SDS). METHODS: Twenty-six
      adult male Wistar rats were randomized into normal control group (n=6), model
      group (n=8), saline + model (saline) group (n=6) and acupuncture + model
      (acupuncture) group (n=6). The spleen deficiency syndrome model was duplicated by
      intragastric perfusion of 50% alcohol (1 mL/100 g, once) and vinegar (pH 3, 1
      mL/100 g, once daily for 10 d). Bilateral "Zusanli" (ST 36) was punctured with
      filiform needles which were manipulated for 1 min after insertion and retained
      for 20 min. The treatment was conducted once daily for 10 days. The contents of
      serum testosterone(T) and estradiol(E2)were detected by radioimmunoassay. The
      rats' physical strength was detected by exhausted swimming test in cool water.
      RESULTS: In comparison with the normal group, the duration of exhausted swimming,
      serum T and E2 contents and T/E, were decreased significantly in the model group
      (P < 0.05). Compared with the model group, the duration of exhausted swimming,
      serum T and E2 contents and T/E2 in the acupuncture group were upregulated
      significantly (P < 0.05). No significant differences were found between the
      saline and control groups (P > 0.05). CONCLUSION: Acupuncture of "Zusanli" (ST
      36) is able to reverse SDS-induced decrease of sexual hormones in spleen
      deficiency syndrome rats, which may contribute to its effect in improving
      physical strength.

PMID- 21942181
TI  - [Effect of electroacupuncture on serum proinflammatory cytokine levels and
      pancreatic nuclear factor kappa-b expression in acute pancreatitis rats].
AB  - OBJECTIVE: To observe the effects of electroacupuncture (EA) of "Zusanli" (ST 36)
      on serum TNF-alpha and IL-6 contents and pancreatic nuclear factor kappa-B (NF
      kappaB) expression in acute pancreatitis rats. METHODS: Sixty-six male SD rats
      were randomly divided into sham operation (sham), model and EA groups (n=22).
      Acute pancreatitis model was established by intra-pancreatic duct injection of
      3.5% sodium taurocholate (0.1 mL/100 g). EA (2 Hz /100 Hz, 2 mA) was applied to
      bilateral ST 36 for 30 min after modeling and at the end of the experiment. The
      animals were killed at 3 h (n=7), 6 h (n=7) and 12 h (n=8) after modeling. The
      expression of pancreatic NF-,cB P65 was detected by immunohistochemical staining,
      and serum TNF-alpha and IL-6 contentswere determined by ELISA. The pathological
      changes of pancreatic tissue were displayed by H. E. staining and the quantity of
      ascite was measured by electronic balance. RESULTS: The pathologic score, ascite
      quantity, serum TNFalpha and IL-6 contents, and pancreatic NF-kappaB P 65
      expression levels at 3 h, 6 h and 12 h after modeling were significantly higher
      in the model group than in the sham group (P < 0.05). Compared with the model
      group, the pathologic score, ascite quantity, serum TNF-alpha and IL-6 contents,
      and pancreatic NF-kappaB P 65 expression levels at 3 h, 6 h and 12 h were
      significantly decreased in the EA group (P < 0.05). Microscopic observation
      displayed that the necrosis of the pancreatic acinar cells and infiltration of
      inflammatory cells were lighter in the EA group than in the model group.
      CONCLUSION: EA at ST 36 is able to down-regulate sodium taurocholate injection
      incduced increase of serum TNF-alpha and IL-6 contents, and pancreatic NF-kappaB
      P65 expression level in acute pancreatitis rats, which may contribute to its
      effect in relieving necrosis of the pancreatic acinar cells and infiltration of
      pancreatic inflammatory cells.

PMID- 21942182
TI  - [Influence of acupuncture of Zusanli (ST 36) on connectivity of brain functional
      network in healthy subjects].
AB  - OBJECTIVE: To observe the effect of acupuncture of Zusanli (ST 36) on
      electroencephalogram (EEG) so as to probe into its law in regulating the
      interconnectivity of brain functional network. METHODS: A total of 9 healthy
      young volunteer students (6 male, 3 female) participated in the present study.
      They were asked to take a dorsal position on a test-bed. EEG signals were
      acquired from 22 surface scalp electrodes (Fp1, Fp2, F7, F3, F2, F4, F8, A1, T3,
      C3, C2, C4, T4, A2, T5, P3, P2, P4, T6, O2, O1 and O2) fixed on the subject's
      head. Acupuncture stimulation was applied to the right Zusanli (ST 36) by
      manipulating the filiform needle with uniform reducing-reinforcing method and at
      a frequency of about 50 cycles/min for 2 min. Then the stimulation was stopped
      for 10 min, and repeated once again (needle-twirling frequency: 150 and 200
      cycles/min), 3 times altogether. The acquired EEG data were analyzed by using
      coherence estimation method, average path length, average clustering coefficient,
      and the average degree of the articulation points (nodes) for analyzing the
      synchronization of EEG signals before, during and after acupuncture. RESULTS: In
      comparison with pre-acupuncture, the coherence amplitude values of EEG-delta (1-4
      Hz) and y (31-47 Hz) waves were increased significantly after acupuncture of ST
      36. No significant changes were found in the amplitude values of EEG-theta (5-8
      Hz), -alpha (9-13 Hz) and-beta (14-30 Hz) waves after acupuncture stimulation.
      During and after acupuncture, the synchronism values of EEG-delta waves of
      different leads and numbers of interconnectivity between every two brain
      functional regions in majority of the 9 volunteers were increased clearly. In all
      volunteers, the degree values of all nodes except A1 and A2, the average
      clustering coefficients along with the increase of the threshold (r), and the
      average path lengths of the brain functional network of EEG-delta waves during
      and after acupuncture were also increased evidently (the latter two items, P <
      0.05), suggesting an increase of the information exchange and functional
      connectivity of different brain regions. CONCLUSION: Acupuncture of Zusanli (ST
      36) can increase the amplitude and synchronization of EEG-delta waves of
      different leads, and potentiate the functional interconnectivity of brain
      functional network.

PMID- 21942183
TI  - [Effect of acupuncture on serum leptin level in patients with type II diabetes
      mellitus].
AB  - OBJECTIVE: To study the relationship between serum leptin and insulin resistance,
      and to analyze the effect of acupuncture on serum leptin level in patients with
      type-II diabetes mellitus (DM). METHODS: A total of 80 type-II DM patients were
      randomized into acupuncture and medication groups. Acupuncture was applied to
      Yishu (EX), Feishu (BL13), Pishu (BL 20), etc. according to syndrome
      identification. The treatment was given once every other day for 12 weeks. For
      patients in the medication group, Glibenclamide (2.5-7.5 mg/time, 1-2 times/d
      according to blood sugar level) was given for 12 weeks. Fasting blood glucose
      (FBG), fasting insulin (FINS) and fasting leptin (FLP) were detected by using
      glucose oxidase method, radioimmunoassay and ELISA, respectively. Insulin
      sensitivity index (ISI) and homeostasis model assessment-insulin resistance (HOMA
      IR) were calculated. RESULTS: In comparison with pre-treatment, FBG levels and
      HOMA-IR in both acupuncture and medication groups, and FINS and FLP levels in the
      acupuncture group were decreased significantly (P < 0.01), while ISI in both
      acupuncture and medication groups, and FINS level in the medication group were
      increased remarkably after the treatment (P < 0.01). Comparison between two
      groups showed that after the treatment, FINS and FLP levels, and HOMA-IR of the
      acupuncture group were considerably lower than those of the medication group (P <
      0.01), while ISI of the acupuncture group was significantly higher than that of
      the medication group (P < 0.01). CONCLUSION: Acupuncture therapy is effective in
      lowering FLP level, which may contribute to its clinical effect in improving type
      II DM.

PMID- 21942184
TI  - [Observation on therapeutic effect of preoperational catgut implantation at
      acupoint for hemorrhoid operation-induced pain in patients].
AB  - OBJECTIVE: To assess the preemptive analgesia effect of catgut implantation in
      Chengshan (BL 57) area on hemorrhoid operation-induced pain and the security, so
      as to find a new method for easing post-operative pain of hemorrhoid. METHODS: A
      total of 120 cases of mixed hemorrhoids patients were randomly divided into the
      catgut implantation group and medication group (n=60). In implantation group, a
      piece of catgut was embedded into bilateral BL 57 acupoint area half an hour
      before surgery. Patients of the medication group were asked to orally take
      Tramadol Hydrochloride Capsules (100 mg) after the surgery. The pain score of
      mixed hemorrhoids patients was evaluated 5, 24, 48, 72 and 96 h after operation
      by using visual analogue scales (VAS). The complications, analgesics use and
      adverse reactions were recorded simultaneously. RESULTS: Comparison between two
      groups showed that the VAS scores of the catgut implantation group at 5, 24, 48,
      72 and 96 h after operation were significantly lower than those of the medication
      group (P < 0.05). The incidence of complications of uroschesis and hydroncus,
      adverse reactions of nausea, vomiting and vertigo, and the number of patients
      using Sauteralgyl were significantly lower in the catgut implantation group than
      in the medication group (P < 0.05). CONCLUSION: Catgut implantation at BL 57 can
      effectively relieve the postoperative pain, reduce postoperative adverse
      reactions and complications in mixed hemorrhoids patients.

PMID- 21942185
TI  - [Primary anylasis on the methodology and strategies for studying mechanisms of
      acu-moxibustion by using metabonomics].
AB  - Metabonomics is a newly emerging modern technology in the Post-genome era and has
      been being used widely in the study on modern Chinese medicine. But it have been
      rarely used in the study on acupuncture therapy. In the present paper, the
      authors introduce the unique advantages of metabonomics in the systemtic biology
      and its widespread studying basis in the field of modern Chinese medicine.
      Metabonomics and Chinese medicine including acupuncturology are of some similar
      characteristics such as entirety, comprehensiveness and dynamic changes.
      Moreover, the authors make a primary discussion and strategic analysis on the key
      issues of researches about sham acupuncture, chrono-acupuncture, mechanisms of
      acu-moxibustion underlying improvement of clinical severe disorders and various
      indications problems, regularities of combination of acupoints in different
      recipes, etc. by using metabonomics.

PMID- 21942186
TI  - [Survey of clinical and experimental researches on mechanisms of acupuncture
      treatment of bronchial asthma].
AB  - In the present paper, the authors review the development of experimental and
      clinical studies on acupuncture treatment of bronchial asthma in recent 10 years.
      Regarding clinical studies, results showed that acupuncture could (1) regulate
      cardiac-pulmonary function; and (2) adjust immune state and relieve inflammatory
      reactions in bronchial asthma patients. Animal experiments showed that
      acupuncture could function in (1) improving pulmonary function; (2) reducing
      accumulation of the peripheral eosinophile granulocytes (EOS), relieving the
      infiltration of inflammatory cells in the air-passage mucosa and promoting the
      apoptosis of EOS in the lung and air-passages; (3) down-regulating the expression
      of air-passage remodeling-related protein insulin growth factor-1; (4)
      suppressing the secretion of tumor necrosis factor and endothelin; (5)
      attenuating allergic reaction; (6) regulating neuroendocrine activity; and (7)
      modulating intracellular second messenger activities. However, rigorous clinical
      study design is not enough, so that the reliability of the results is limited. In
      spite of many indicators of animal experiments have been selected, but their
      correlations are not in close association, resulting in poor complementation and
      mutual identification of the acquired findings. For this reason, its clinical
      efficacies need to be researched further according to principles of evidence
      based medicine.

PMID- 21942187
TI  - [Effect of somatostatin on functions of acupuncture meridians].
AB  - Our previous studies have showed that analogue electroacupuncture (EA) could
      induce a transmission of electrical signals along meridians, and excitatory
      neurotransmitters such as substance P and glutamate were involved in the
      transmission process. In recent studies, our results showed that somatostatin and
      its receptors played a dose-dependent tonic inhibition on the discharge rates of
      original and adjacent nerves innervating the acupoints. In addition, there
      existed an interaction between somatostatin and glutamate. These results suggest
      that the balance between excitatory and inhibitory neurotransmitters plays an
      important role in the function activities of acupoints and meridians.

PMID- 21942188
TI  - Water- and wastewater-related disease and infection risks: what is an appropriate
      value for the maximum tolerable additional burden of disease?
AB  - The maximum additional burden of water- and wastewater-related disease of 10-6
      disability-adjusted life year (DALY) loss per person per year (pppy), used in the
      WHO Drinking-water Quality Guidelines and the WHO Guidelines for Wastewater Use
      in Agriculture, is based on US EPA'S acceptance of a 70-year lifetime waterborne
      cancer risk of 10(-5) per person, equivalent to an annual risk of 1.4x10(-7) per
      person which is four orders of magnitude lower than the actual all-cancer
      incidence in the USA in 2009 of 1.8x10(-3) pppy. A maximum additional burden of
      10(-4) DALY loss pppy would reduce this risk to a more cost-effective, but still
      low, risk of 1.4x10(-5) pppy. It would increase the DALY loss pppy in low- and
      middle-income countries due to diarrhoeal diseases from the current level of
      0.0119 pppy to 0.0120 pppy, and that due to ascariasis from 0.0026 pppy to 0.0027
      pppy, but neither increase is of public-health significance. It is therefore
      recommended that the maximum additional burden of disease from these activities
      be increased to a DALY loss of 10(-4) pppy as this provides an adequate margin of
      public-health safety in relation to waterborne-cancer deaths, diarrhoeal disease
      and ascariasis in all countries.

PMID- 21942190
TI  - Influences on the water testing behaviors of private well owners.
AB  - Many private wells in the United States and Canada already are contaminated, or
      are at risk of contamination. Regular testing for pathogenic bacteria is one of
      the most concrete measures well owners can use to determine whether or not their
      drinking water quality is safe. This study explored the factors and causal
      relationships that influence well owner water quality testing behavior. In-depth,
      semi-structured interviews were used to evaluate the stewardship behavior of 22
      well owners in Ontario, Canada. Causal networks were created for each
      interviewee. These were then aggregated to determine key factors and causal
      relationships. The research revealed that motivations for regular testing include
      peace of mind and reassurance. Barriers include complacency, inconvenience, and
      lack of a perceived problem. Knowledge and better information by themselves were
      found to provide a weak basis for changing behavior. Implications of this
      research for promoting water testing behavior are discussed.

PMID- 21942189
TI  - Human norovirus infection of caco-2 cells grown as a three-dimensional tissue
      structure.
AB  - Human norovirus (hNoV) infectivity was studied using a three-dimensional model of
      large intestinal epithelium. Large intestine Caco-2 cells were grown in rotating
      wall vessel bioreactors for 18-21 days at 37 degrees C and then transferred to 24
      well tissue culture plates where they were infected with GI.1 and GII.4 human
      noroviruses collected from human challenge trials and various outbreak settings,
      respectively. Compared with uninfected cells, transmission micrographs of
      norovirus-infected cells displayed evidence of shortening or total loss of apical
      microvilli, and vacuolization. Quantitative reverse transcription real-time PCR
      (qRT-PCR) indicated an approximate 2-3 log10 increase in viral RNA copies for the
      infected cells. A passage experiment examined both the ability for continued
      viral RNA and viral antigen detection. In the passaged samples 1.01x10(6) copies
      ml(-1) were detected by qRT-PCR. Immune electron microscopy using primary
      antibody to hNoV GI.1 capsids in conjunction with 6 nm gold-labelled secondary
      antibodies was performed on crude cellular lysates. Localization of antibody was
      observed in infected but not for uninfected cells. Our present findings, coupled
      with earlier work with the three-dimensional small intestinal INT407 model,
      demonstrate the utility of 3-D cell culture methods to develop infectivity assays
      for enteric viruses that do not readily infect mammalian cell cultures.

PMID- 21942191
TI  - A novel genetic marker for the rapid detection of Bacteroides fragilis in
      recreational water as a human-specific faecal indicator.
AB  - Bacteroides spp. has gained substantial interest among the suggested potential
      candidates for alternative faecal indicators for untreated recreational waters by
      the US EPA. Interest in Bacteroides as a faecal indicator is based upon the
      relative abundance of selected members of the Bacteroides genus in the human
      colon and human faeces. In this study, we developed a real-time PCR detection
      system based on gyrase B subunit genes (gyrB) specific to Bacteroides fragilis.
      The gryB-based method was compared with previously described 16S rRNA-based real
      time qPCR methods and evaluated for specificity, sensitivity and robustness in
      detecting B. fragilis from untreated recreational water impacted by human and non
      human faecal sources. The new gyrB-based system only detected B. fragilis,
      whereas the 16S rRNA-based methods generated cross-amplifications with other
      Bacteroides and Prevotella species. We used a procedure of prefiltration,
      filtration, sonication and DNA concentration in order to improve the DNA
      extraction efficiency and the sensitivity of the real-time PCR while removing
      interference. The amplification and sequencing of PCR products generated by the
      gyrB-based method confirmed that gyrB-amplified sequences only contained B.
      fragilis. This rapid method is useful for quantifying faecal contamination and
      may assist beach and watershed managers in elucidating possible contamination
      sources.

PMID- 21942192
TI  - Are microbial indicators and pathogens correlated? A statistical analysis of 40
      years of research.
AB  - Indicator organisms are used to assess public health risk in recreational waters,
      to highlight periods of challenge to drinking water treatment plants, and to
      determine the effectiveness of treatment and the quality of distributed water.
      However, many have questioned their efficacy for indicating pathogen risk. Five
      hundred and forty cases representing independent indicator-pathogen correlations
      were obtained from the literature for the period 1970-2009. The data were
      analyzed to assess factors affecting correlations using a logistic regression
      model considering indicator classes, pathogen classes, water types, pathogen
      sources, sample size, the number of samples with pathogens, the detection method,
      year of publication and statistical methods. Although no single indicator was
      identified as the most correlated with pathogens, coliphages, F-specific
      coliphages, Clostridium perfringens, fecal streptococci and total coliforms were
      more likely than other indicators to be correlated with pathogens. The most
      important factors in determining correlations between indicator-pathogen pairs
      were the sample size and the number of samples positive for pathogens. Pathogen
      sources, detection methods and other variables have little influence on
      correlations between indicators and pathogens. Results suggest that much of the
      controversy with regards to indicator and pathogen correlations is the result of
      studies with insufficient data for assessing correlations.

PMID- 21942193
TI  - Levels and patterns of fecal indicator bacteria in stormwater runoff from
      homogenous land use sites and urban watersheds.
AB  - Routine stormwater monitoring programs focus on quantification of average fecal
      indicator bacteria (FIB) concentration at the terminal watershed discharge point.
      While important for permit compliance, such monitoring provides little insight
      into relative bacteria levels from different land use types or the mechanisms
      that influence FIB concentrations. The goal of this study was to quantify the
      relative levels and flux patterns of Escherichia coli, enterococci, and total
      coliforms from representative land use (LU) types. Bacteria concentrations were
      measured over the entire storm duration from 8 different LU types over 13 storm
      events in 5 southern California watersheds during the 2000-2005 storm seasons. In
      addition, runoff samples were collected from 8 bottom of the watershed mass
      emission (ME) sites. Intra-storm and intra-season patterns were investigated in
      order to identify mechanisms that influence patterns of FIB concentrations. Mean
      FIB event mean concentrations (EMCs) at LU sites ranged from 10(3) to 10(5)
      MPN/100 mi. Recreational (horse stables) LU sites contributed significantly
      higher storm EMCs than other LU types. Early season storms repeatedly produced
      higher EMCs than comparably sized late season storms. For most storms sampled,
      the highest bacterial concentrations occurred during the early phases of
      stormwater runoff with peak concentrations usually preceding peak flow.

PMID- 21942194
TI  - Managing risks from virus intrusion into water distribution systems due to
      pressure transients.
AB  - Low or negative pressure transients in water distribution systems, caused by
      unexpected events (e.g. power outages) or routine operation/maintenance
      activities, are usually brief and thus are rarely monitored or alarmed. Previous
      studies have shown connections between negative pressure events in water
      distribution systems and potential public health consequences. Using a
      quantitative microbial risk assessment (QMRA) model previously developed, various
      factors driving the risk of viral infection from intrusion were evaluated,
      including virus concentrations external to the distribution system, maintenance
      of a disinfectant residual, leak orifice sizes, the duration and the number of
      nodes drawing negative pressures. The most sensitive factors were the duration
      and the number of nodes drawing negative pressures, indicating that mitigation
      practices should be targeted to alleviate the severity of low/negative pressure
      transients. Maintaining a free chlorine residual of 0.2 mg/L or above is the last
      defense against the risk of viral infection due to negative pressure transients.
      Maintaining a chloramine residual did not appear to significantly reduce the
      risk. The effectiveness of ensuring separation distances from sewer mains to
      reduce the risk of infection may be system-specific. Leak detection/repair and
      cross-connection control should be prioritized in areas vulnerable to negative
      pressure transients.

PMID- 21942195
TI  - Virus removal efficiency of Cambodian ceramic pot water purifiers.
AB  - Virus removal efficiency is described for three types of silver-impregnated,
      ceramic water filters (CWFs) produced in Cambodia. The tests were completed using
      freshly scrubbed filters and de-ionized (DI) water as an evaluation of the
      removal efficiency of the virus in isolation with no other interacting water
      quality variables. Removal efficiencies between 0.21 and 0.45 log are evidenced,
      which is significantly lower than results obtained in testing of similar filters
      by other investigators utilizing surface or rain water and a less frequent
      cleaning regime. Other experiments generally found virus removal efficiencies
      greater than 1.0 log. This difference may be because of the association of
      viruses with suspended solids, and subsequent removal of these solids during
      filtration. Variability in virus removal efficiencies between pots of the same
      manufacturer, and observed flow rates outside the manufacturer's specifications,
      suggest tighter quality control and consistency may be needed during production.

PMID- 21942196
TI  - Prevalence study of Simkania negevensis in cooling towers in Spain.
AB  - Simkania negevensis is an obligate intracellular bacterium grouped into the order
      Chlamydiales. This new amoeba-resistant intracellular bacterium might represent a
      novel etiologic agent of bronchiolitis and community-acquired pneumonia and
      occurs in aquatic habitats such as drinking water and reclaimed wastewater.
      Another amoeba-related bacterium, Legionella pneumophila, is an etiologic agent
      of pneumonia transmitted by environmental aerosols or contaminated water/air
      cooling systems. These transmission pathways are important in the natural history
      of Legionellae infections and possibly other intracellular microorganisms such as
      Parachlamydiaceae; thus, understanding the feasibility of Simkania infection by
      these routes is relevant. In the present work, we investigated the prevalence of
      this newly identified pathogenic bacterium in cooling towers by quantitative PCR
      (qPCR) and its possible relationship with Legionella pneumophila co-infection.
      Our results show Simkania detection in 2 of 70 cooling towers analyzed. To our
      knowledge, this report is the first describing Simkania negevensis detection in
      this category of environmental water samples.

PMID- 21942197
TI  - A performance assessment of arsenic-iron removal plants in the Manikganj district
      of Bangladesh.
AB  - In Bangladesh, arsenic contamination of groundwater, microbial contamination of
      surface water and seasonally variable rainfall make reliable access to acceptable
      quality drinking water a challenge. Arsenic-iron removal plants (AIRPs) are a
      relatively inexpensive way of removing arsenic from groundwater for access to
      safer drinking water. This study evaluated the performance of 21 (of 105) AIRPs
      installed by a local non-governmental organization (Society for People's Action
      in Change and Equity) with financial assistance from the Australian High
      Commission, Dhaka, under the Direct Aid Program of the Australian Government. All
      AIRPs achieved the Bangladesh standard for arsenic in drinking water of 50 microg
      L(-1) and 17 achieved the World Health Organization guideline of 10 microg L(-1).
      The AIRPs removed 87% of influent arsenic, on average. After cleaning, poor
      arsenic and iron removal was observed for about 2 days due to inadequate
      residence time. Chemical processes that may influence AIRP performance are also
      discussed herein, including iron and arsenic oxidation, arsenic co-precipitation
      with iron, multiple iron additions, interference by organics, and iron
      crystallization. Effluent faecal coliform counts were generally low, though were
      slightly higher than influent counts. Overall, AIRPs were shown to possess
      considerable promise for use in areas with high natural iron where users are
      concerned about arsenic and/or iron in their drinking water.

PMID- 21942198
TI  - Water quality indices based on bioassessment: the biotic indices.
AB  - Water quality indices (WQIs), which translate numerical values of several water
      quality characteristics of a sample into a single value, play a very important
      role in the monitoring, comparison and control of water quality. The WQIs of
      modern and post-modern times have been almost exclusively based on physical and
      chemical characteristics, and have seldom included 'biological' characteristics
      other than biochemical oxygen demand (BOD) and faecal coliforms. During the last
      three decades of the 20th century, indices based on bioassessment have been
      increasingly used in some developed countries, besides South Africa and Serbia,
      to complement the conventional WQIs, but the rest of the world continues to base
      its WQIs predominantly on physical and chemical characteristics. The serious
      drawbacks of this approach have been elucidated in this paper and, against that
      background, the state-of-the-art of biotic indices has been summarized. The paper
      makes a strong case for greater reliance on bioassessment-based WQls, especially
      by developing countries, to strengthen the diagnostic value of the conventional
      WQls.

PMID- 21942199
TI  - Incorporation of the Multiple Barrier Approach in drinking water risk assessment
      tools.
AB  - A number of existing risk assessment tools make reference to, or incorporate, a
      Multiple Barrier Approach to drinking water safety. Three waterborne disease
      outbreaks that occurred in developed nations were used as case studies to test a
      selected set of risk assessment tools. The outbreaks were used to determine how
      well the risk assessment tools identify hazards and vulnerabilities associated
      with different barriers to drinking water contamination.

PMID- 21942200
TI  - Detection of assemblages A and B of Giardia duodenalis in water and sewage from
      Sao Paulo state, Brazil.
AB  - Giardia duodenalis is a protozoan that parasitizes humans and other mammals and
      causes giardiasis. Although its isolates have been divided into seven
      assemblages, named A to G, only A and B have been detected in human faeces.
      Assemblage A isolates are commonly divided into two genotypes, Al and All. Even
      though information about the presence of this protozoan in water and sewage is
      available in Brazil, it is important to verify the distribution of different
      assemblages that might be present, which can only be done by genotyping
      techniques. A total of 24 raw and treated sewage, surface and spring water
      samples were collected, concentrated and purified. DNA was extracted, and a
      nested PCR was used to amplify an 890 bp fragment of the gdh gene of G.
      duodenalis, which codes for glutamate dehydrogenase. Positive samples were cloned
      and sequenced. Ten out of 24 (41.6%) samples were confirmed to be positive for G.
      duodenalis by sequencing. Phylogenetic analysis grouped most sequences with G.
      duodenalis genotype All from GenBank. Only two raw sewage samples presented
      sequences assigned to assemblage B. In one of these samples genotype All was also
      detected. As these assemblages/genotypes are commonly associated to human
      giardiasis, the contact with these matrices represents risk for public health.

PMID- 21942201
TI  - Rainfall and river flows are predictors for beta-glucuronidase positive
      Escherichia coil accumulation in mussels and Pacific oysters from the Dart
      Estuary (England).
AB  - Rainfall and river flows are environmental variables influencing the microbial
      status of bivalve mollusc harvesting areas. This study investigated spatial and
      temporal relationships between rainfall, river flows and concentrations of
      Escherichia coli in mussels (Mytilus spp.) and Pacific oysters (C. gigas) from
      three harvesting areas in the Dart Estuary over the period 1996-2009. Mussels
      growing on the riverbed were found to be more contaminated than oysters growing
      in the water column. A step change in the levels of the microbial indicator was
      identified in both species from all harvesting areas. The highest levels of E.
      coli were detected when total rainfall exceeded 2 mm and water levels in the main
      tributaries exceeded the mean flow. The magnitude of response in levels of E.
      coli to these hydrological events varied between species and monitoring points,
      but was consistently higher between the 3rd and 4th days after the rainfall
      event. This lag time is assumed to result from catchment topography and geology
      determining peak levels of runoff at the headwaters 12-24 h after rainfall
      events. It is considered that future risk management measures may include
      sampling targeting hydrograph events.

PMID- 21942202
TI  - Opportunistic pathogens relative to physicochemical factors in water storage
      tanks.
AB  - Household water in Oman, as well as in other countries in the region, is stored
      in tanks placed on house roofs that can be subjected to physicochemical factors
      which can promote microbial growth, including pathogens and opportunistic
      pathogens which pose health risks. Water samples were collected from 30 houses in
      a heavily populated suburb of Muscat. The tanks used were either glass reinforced
      plastic (GRP), polyethylene or galvanised iron (GI). Heterotrophic bacteria,
      coliforms, faecal coliforms and iron sulphur bacteria varied significantly in the
      three tanks. Yeast and mould count showed significant variations. Isolation of
      Aeromonas spp., fluorogenic and pathogenic Pseudomonas, Pasteurella, Salmonella,
      Serratia and Tatumella, and Yersinia and Legionella in biofilms varied in the
      three tanks. The fungi isolates in the three tanks were Penicillium, Cladosporium
      and Aspergillus. Nephelometric turbidity unit, threshold odour number and free
      chlorine varied significantly in the three tanks. True colour unit values did not
      show a significant difference; however, GRP tanks had algae, autotrophic and
      pigmented microorganisms. In addition, GI tanks had sediments and corrosion. The
      results of this investigation are important to evaluate the status of the present
      household water tanks in countries with high annual temperatures, which may
      affect public health.

PMID- 21942203
TI  - Evaluation of pot-chlorination of wells during a cholera outbreak, Bissau, Guinea
      Bissau, 2008.
AB  - We evaluated the ability of UNICEF-designed pot-chlorinators to achieve
      recommended free residual chlorine (FRC) levels in well water in Bissau, Guinea
      Bissau, during a cholera outbreak. Thirty wells were randomly selected from six
      neighbourhoods. Pot-chlorinators--perforated plastic bottles filled with gravel,
      sand and calcium hypochlorite granules--were placed in each well. FRC was
      measured before and 24, 48 and 72 h after placement and compared with World
      Health Organization (WHO)-recommended levels of 21 mg L(-1) for well water during
      cholera outbreaks and 0.2-5 mg L 1 in non-outbreak settings. Presence of well
      covers, distance from wells to latrines, and rainfall were noted. Complete post
      chlorination data were collected from 26 wells. At baseline, no wells had
      FRC>0.09 mg L(-1). At 24, 48 and 72 h post-chlorination, 4 (15%), 1 (4%) and 0
      wells had FRC>or=1 mg L(-1) and 16 (62%), 4 (15%) and 1 (4%) wells had FRC
      between 0.2 and 5 mg L(-1), respectively. Several families reported discontinuing
      household water chlorination after wells were treated with pot-chlorinators. Pot
      chlorinators failed to achieve WHO-recommended FRC levels in well water during a
      cholera outbreak, and conveyed a false sense of security to local residents. Pot
      chlorination should be discouraged and alternative approaches to well-water
      disinfection promoted.

PMID- 21942204
TI  - Microbial safety of air-dried and rewetted biosolids.
AB  - To assess microbial safety of treated sewage sludge (biosolids), we examined the
      inactivation of microbial indicators for potential bacterial, viral and protozoan
      pathogens. The levels of indicators were determined throughout the air-drying and
      storage phases of anaerobically digested sewage sludge. Samples were collected
      from two wastewater treatment plants (WWTPS) in Victoria, Australia. Established
      methods were applied for analysis of bacteria and coliphages, based on membrane
      filtration and layered plates, respectively. In the pan drying phase, the
      prevalence of Escherichia coli was reduced by >5 log10 compared with sludge
      entering the pan. Thus, after pan drying of 8-11 months at WWTP A and 15 months
      at WWTP B, the numbers of E. coli were reduced to below 10(2) cfu/g dry solids
      (DS). This level is acceptable for unrestricted use in agriculture in Australia
      (P1 treatment grade), the UK (enhanced treatment status) and the USA (Class A
      pathogen reduction). Coliphage numbers also decreased substantially during the
      air-drying phase, indicating that enteric viruses are also likely to be destroyed
      during this phase. Clostridium perfringens appeared to be an overly conservative
      indicator. Survival, but not regrowth, of E. coli or Salmonella was observed in
      rewetted biosolids (15-20% moisture content), after being seeded with these
      species, indicating a degree of safety of stored biosolids upon rewetting by
      rain.

PMID- 21942205
TI  - Bacteriological assessment of drinking water supply options in coastal areas of
      Bangladesh.
AB  - This study was conducted to assess the bacteriological quality of alternative
      drinking water supply options in southwest coastal areas of Bangladesh. A total
      of 90 water samples were collected during both dry and wet seasons from household
      based rainwater harvesting systems (RWHSS), community based rain water harvesting
      systems (CRWHSs), pond-sand filters (PSFs) and ponds. The samples were evaluated
      for faecal coliform, Escherichia coli and Heterotrophic Plate Count, as well as
      Vibrio cholerae, Salmonella spp., Shigella spp. and Pseudomonas spp. Physico
      chemical parameters (pH, electrical conductivity, and color) were also examined.
      In addition, sanitary inspections were conducted to identify faecal contamination
      sources. All options showed varying degrees of indicator bacterial contamination.
      The median E. coli concentrations measured for RWHSs, CRWHSS, PSFS, and ponds
      were 16, 7, 11, and 488 cfu/100 ml during the wet season, respectively. Vibrio
      cholerae 01/0139, Salmonella and Shigella spp. were not found in any samples.
      However, Vibrio cholerae Non-01/Non-0139 and Pseudomonas spp. were isolated from
      74.4% and 91.1% of the water samples collected during the wet season. A maximum
      pH of 10.4 was found in CRWHSS. Estimation of the disease burden for all options
      in disability adjusted life years (DALYs) showed an increased disease burden
      during the wet season. According to sanitary inspections, poor maintenance and
      unprotected ponds were responsible for rainwater and PSF water contamination,
      respectively. The findings of the present study suggest that alternative drinking
      water supply options available in southwest coastal Bangladesh pose a substantial
      risk to public health.

PMID- 21942207
TI  - Characterization of the organic ligand shell of semiconductor quantum dots by
      fluorescence quenching experiments.
AB  - We present the characterization of the organic ligand shell of CdSe/Cd(x)Zn(1
      x)S/ZnS nanoparticles by means of fluorescence quenching experiments. Both
      electron scavengers and acceptors for resonance energy transfer were employed as
      probes. Different quenching behavior for short and long chain thiol ligands in
      water was found. It could be shown that poly(ethylene oxide) (PEO)-capping of the
      particles comprises a densely packed inner shell and a loosely packed outer shell
      in which ions and small molecules diffuse unhindered. A quantitative uptake of
      quencher molecules into the PEO shell was observed, through which the particle
      volume including the ligand sphere could be determined.

PMID- 21942208
TI  - Free energy landscapes of ion coordination in aqueous solution.
AB  - We show how the fruitful concept of free energy landscape, as  invoked in the
      description of complex biological systems, can be rather easily extended to build
      up a simple and accurate picture about solvent coordination around ions. This may
      represent a revealing key element for the qualitative and quantitative physical
      chemical interpretation of a large number of phenomena occurring in solution,
      such as water exchange mechanisms, ion mobility, solvation dynamics, ion channel
      selectivity, and so on. In particular, using a computational approach rooted into
      molecular dynamics simulations and enhanced sampling techniques, we show how the
      free energy landscapes of ion coordination in solution can be very easily and
      accurately obtained in a number of illustrative examples.

PMID- 21942206
TI  - Pseudohyperphosphorylation has differential effects on polymerization and
      function of tau isoforms.
AB  - The microtubule-associated protein tau exists as six isoforms created through the
      splicing of the second, third, and tenth exons. The isoforms are classified by
      their number of N-terminal exons (0N, 1N, or 2N) and by their number of
      microtubule-binding repeat regions (3R or 4R). Hyperphosphorylated isoforms
      accumulate in insoluble aggregates in Alzheimer's disease and other tauopathies.
      These neurodegenerative diseases can be categorized based on the isoform content
      of the aggregates they contain. Hyperphosphorylated tau has the general
      characteristics of an upward electrophoretic shift, decreased microtubule
      binding, and an association with aggregation. Previously we have shown that a
      combination of seven pseudophosphorylation mutations at sites phosphorylated by
      GSK-3beta, referred to as 7-Phos, induced several of these characteristics in
      full-length 2N4R tau and led to the formation of fewer but longer filaments. We
      sought to determine whether the same phosphorylation pattern could cause
      differential effects in the other tau isoforms, possibly through varied
      conformational effects. Using in vitro techniques, we examined the
      electrophoretic mobility, aggregation properties, and microtubule stabilization
      of all isoforms and their pseudophosphorylated counterparts. We found that
      pseudophosphorylation affected each isoform, but in several cases certain
      isoforms were affected more than others. These results suggest that
      hyperphosphorylation of tau isoforms could play a major role in determining the
      isoform composition of tau aggregates in disease.

PMID- 21942209
TI  - Molecular tensile machines: intrinsic acceleration of disulfide reduction by
      dithiothreitol.
AB  - Significant tension on the order of 1 nN is self-generated along the backbone of
      bottlebrush macromolecules due to steric repulsion between densely grafted side
      chains. The intrinsic tension is amplified upon adsorption of bottlebrush
      molecules onto a substrate and increases with grafting density, side chain
      length, and strength of adhesion to the substrate. These molecules were employed
      as miniature tensile machines to study the effect of mechanical force on the
      kinetics of disulfide reduction by dithiothreitol (DTT). For this purpose,
      bottlebrush macromolecules containing a disulfide linker in the middle of the
      backbone were synthesized by atom transfer radical polymerization (ATRP). The
      scission reaction was monitored through molecular imaging by atomic force
      microscopy (AFM). The scission rate constant increases linearly with the
      concentration of DTT and exponentially with mechanical tension along the
      disulfide bond. Moreover, the rate constant at zero force is found to be
      significantly lower than the reduction rate constant in bulk solution, which
      suggests an acidic composition of the water surface with pH = 3.7. This work
      demonstrates the ability of branched macromolecules to accelerate chemical
      reactions at specific covalent bonds without applying an external force.

PMID- 21942210
TI  - Nanocrystalline electrodes based on nanoporous-walled WO3 nanotubes for organic
      dye-sensitized solar cells.
AB  - Nanoporous-walled tungsten oxide (WO(3)) nanotubes (NTs), which had a more
      positive conduction band edge level compared to that of TiO(2), were applied to
      various organic dyes for dye-sensitized solar cells (DSSCs). The dye-sensitized
      WO(3) NTs displayed photosensitization for the organic dyes whose lowest
      unoccupied molecular orbital (LUMO) level was relatively positive to the
      conventional TiO(2) electrode and, thus, not applicable for electron injection to
      the TiO(2) electrode. Electron transport time and electron lifetime for the WO(3)
      electrode in the DSSCs were investigated. In comparison to the DSSCs based on
      TiO(2), SnO(2), and In(2)O(3), the WO(3) DSSCs displayed the longest lifetime. On
      the other hand, non-diffusion-like electron transport may be an issue to apply
      WO(3) for the DSSCs.

PMID- 21942211
TI  - Excited-state intramolecular proton transfer molecules bearing o-hydroxy
      analogues of green fluorescent protein chromophore.
AB  - o-Hydroxy analogues, 1a-g, of the green fluorescent protein chromophore have been
      synthesized. Their structures and electronic properties were investigated by X
      ray single-crystal analyses, electrochemistry, and luminescence properties. In
      solid and nonpolar solvents 1a-g exist mainly as Z conformers that possess a
      seven-membered-ring hydrogen bond and undergo excited-state intramolecular proton
      transfer (ESIPT) reactions, resulting in a proton-transfer tautomer emission.
      Fluorescence upconversion dynamics have revealed a coherent type of ESIPT,
      followed by a fast vibrational/solvent relaxation (<1 ps) to a twisted (regarding
      exo-C(5)-C(4)-C(3) bonds) conformation, from which a fast population decay of a
      few to several tens of picoseconds was resolved in cyclohexane. Accordingly, the
      proton-transfer tautomer emission intensity is moderate (0.08 in 1e) to weak
      (~10(-4) in 1a) in cyclohexane. The stronger intramolecular hydrogen bonding in
      1g suppresses the rotation of the aryl-alkene bond, resulting in a high yield of
      tautomer emission (Phi(f) ~ 0.2). In the solid state, due to the inhibition of
      exo-C(5)-C(4)-C(3) rotation, intense tautomer emission with a quantum yield of
      0.1-0.9 was obtained for 1a-g. Depending on the electronic donor or acceptor
      strength of the substituent in either the HOMO or LUMO site, a broad tuning range
      of the emission from 560 (1g) to 670 nm (1a) has been achieved.

PMID- 21942215
TI  - Alloyed (ZnSe)(x)(CuInSe2)(1-x) and CuInSe(x)S(2-x) nanocrystals with a monophase
      zinc blende structure over the entire composition range.
AB  - Metastable zinc blende CuInSe(2) nanocrystals were synthesized by a hot-injection
      approach. It was found that the lattice mismatches between zinc blende CuInSe(2)
      and ZnSe as well as CuInSe(2) and CuInS(2) are only 2.0% and 4.6%, respectively.
      Thus, alloyed (ZnSe)(x)(CuInSe(2))(1-x) and CuInSe(x)S(2-x) nanocrystals with a
      zinc blende structure have been successfully synthesized over the entire
      composition range, and the band gaps of alloys can be tuned in the range from
      2.82 to 0.96 eV and 1.43 to 0.98 eV, respectively. These alloyed
      (ZnSe)(x)(CuInSe(2))(1-x) and CuInSe(x)S(2-x) nanocrystals with a broad tunable
      band gap have a high potential for photovoltaic and photocatalytic applications.

PMID- 21942216
TI  - A chemical reporter for protein AMPylation.
AB  - Protein AMPylation is an emerging post-translational modification, which plays
      key roles in bacterial pathogenesis and cell biology. Enzymes with AMPylation
      activity, referred to as AMPylators, have been identified in several bacterial
      pathogens and eukaryotes. To facilitate the study of this unique modification, we
      developed an alkynyl chemical reporter for detection and identification of
      protein AMPylation substrates. Covalent functionalization of AMPylation
      substrates with the alkynyl reporter in lieu of adenylyl 5'-monophosphate (AMP)
      allows their subsequent bioorthogonal ligation with azide-fluorescent dyes or
      affinity enrichment tags. We show that this chemical reporter is transferred by a
      range of AMPylators onto their cognate protein substrates and allows rapid
      detection and identification of AMPylated substrates.

PMID- 21942217
TI  - Downregulation of MAGI1 associates with poor prognosis of hepatocellular
      carcinoma.
AB  - OBJECTIVE: MAGI1 (membrane-associated guanylate kinase, WW and PDZ domain
      containing 1) plays an important role in stabilization of adherens junctions and
      suppression of invasiveness and metastasis. However, its expression and clinical
      revelance in hepatocellular carcinoma (HCC) are still unknown. So, this study was
      performed to detect the expression and clinical significance of MAGI1 in human
      HCC. METHODS: The mRNA and protein expression levels were examined by using
      reverse transcription-PCR (RT-PCR) and Western blotting in 31 paired HCC and
      paracarcinomatous liver tissues (PCLT). Furthermore, samples of 104 HCC patients
      were determined immunohistochemically for MAGI1 expression and the correlation of
      MAGI1 levels with prognosis was analyzed. RESULTS: The expression levels of MAGI1
      were significantly downregulated in HCCs than those in PCLTs (p < .01).
      Importantly, the decreased expression of MAGI1 correlated with multiple tumor
      nodules (p < .05), absence of capsular formation (p < .05), worse Edmondson
      Steiner grade (p < .05), vein invasion (p < .01), shortened median overall
      survival time (25 versus 42 months; p = .013), and disease-free survival time (20
      versus 40 months; p = .018) of HCC. Multivariable Cox regression analysis
      revealed that MAGI1 expression level was an independent factor for prognosis (p =
      .038). CONCLUSIONS: MAGI1 expression is decreased in HCC, which correlates with
      poor prognosis, suggesting MAGI1 as a novel prognostic marker for HCC.

PMID- 21942218
TI  - Investigation of isomeric transformations of chlorogenic acid in buffers and
      biological matrixes by ultraperformance liquid chromatography coupled with hybrid
      quadrupole/ion mobility/orthogonal acceleration time-of-flight mass spectrometry.
AB  - Ultraperformance liquid chromatography coupled with hybrid quadrupole/ion
      mobility/orthogonal acceleration time-of-flight (oa-TOF) mass spectrometry (UPLC
      IM-MS) was used to study the isomeric transformations of trans-5-caffeoylquinic
      acid, an extremely active compound present in multiple vegetables, fruits, and
      beverages. The UPLC/oa-TOF MS results proved that in phosphate buffer (pH 7.4),
      plasma, or urine sample, trans-5-caffeoylquinic acid first isomerizes to trans-4
      caffeoylquinic acid and then to trans-3-caffeoylquinic acid by intramolecular
      acyl migration. When exposed to UV light, trans-3-, -4-, and -5-caffeoylquinic
      acids undergo cis/trans isomerization to form cis isomers. The isomerization was
      solely dependent on the pH of the matrix, as well as the incubation temperature,
      and was independent of metabolic enzymes. UPLC-IM-MS results revealed that a
      reversible cis/trans isomerization of caffeoylquinic acids could also be induced
      by the electric field in an electrospray source. Thus, understanding the possible
      role of electric field-induced isomerization of caffeoylquinic acids may help
      lessen the confusion between gas phase phenomena and liquid state chemistry when
      applying IM-MS analysis. The comprehensive understanding of caffeoylquinic acid
      isomerization transformations is crucial for the appropriate handling of samples
      and interpretation of experimental data.

PMID- 21942219
TI  - Fornix-based incision for strabismus surgery: the Parks technique revisited.
AB  - The authors revisit the fornix incision for strabismus surgery. This technique,
      first developed by Parks in 1968, has key advantages over the limbal incision and
      ought to be used and taught more commonly. A modified version of this approach is
      described, illustrated with a demonstration video.

PMID- 21942220
TI  - Plasmonic nanoparticle chain in a light field: a resonant optical sail.
AB  - Optical trapping and driving of small objects has become a topic of increasing
      interest in multidisciplinary sciences. We propose to use a chain made of
      metallic nanoparticles as a resonant light sail, attached by one end point to a
      transparent object and propelling it by the use of electromagnetic radiation.
      Driving forces exerted on the chain are theoretically studied as a function of
      radiation's wavelength and chain's alignments with respect to the direction of
      radiation. Interestingly, there is a window in the frequency spectrum in which
      null-torque equilibrium configuration, with minimum geometric cross section,
      corresponds to a maximum in the driving force.

PMID- 21942228
TI  - Changes in adrenomedullin in patients with proliferative diabetic retinopathy.
AB  - PURPOSE: To measure adrenomedullin (ADM) levels in the blood, vitreous fluid and
      fibrous membrane in patients with proliferative diabetic retinopathy (PDR) and
      study its changes in different pathological conditions. METHODS: We used
      radioimmunoassay technique to determine immunoreactive- adrenomedullin (IR-ADM)
      concentrations in the plasma, vitreous samples and fibrous membrane obtained from
      9 control subjects with idiopathic macular hole and 23 patients with PDR
      undergoing vitrectomy. RESULTS: IR-ADM levels in the plasma, vitreous samples and
      fibrous membrane tissues (16.1 +/- 2.91fmol/ml, 9.80 +/- 2.51fmol/ml and 34.8 +/-
      5.22fmol/mg) were all significantly elevated in patients with PDR compared with
      control subjects (11.6 +/- 2.38 fmol/ml, 5.8 +/- 1.64 fmol/ml and 22.4 +/- 1.72
      fmol/mg). The levels of ADM in vitreous were also significantly higher in PDR
      patients with diabetic macular edema (DME) (11.2 +/- 2.36 fmol/ml) than those of
      patients without DME (8.0 +/- 1.11 fmol/ml) and controls (5.8 +/- 1.64 fmol/ml).
      CONCLUSIONS: These findings suggest that ADM may be produced locally in the eyes
      and may correlate with the severity and proliferative reactions of diabetic
      retinopathy.

PMID- 21942221
TI  - Protein assembly at the air-water interface studied by fluorescence microscopy.
AB  - Protein assembly at the air-water interface (AWI) occurs naturally in many
      biological processes and provides a method for creating biomaterials. However,
      the factors that control protein self-assembly at the AWI and the dynamic
      processes that occur during adsorption are still underexplored. Using
      fluorescence microscopy, we investigated assembly at the AWI of a model protein,
      human serum albumin minimally labeled with Texas Red fluorophore. Static and
      dynamic information was obtained under low subphase concentrations. By varying
      the solution protein concentration, ionic strength, and redox state, we changed
      the microstructure of protein assembly at the AWI accordingly. The addition of
      pluronic surfactant caused phase segregation to occur at the AWI, with fluid
      surfactant domains and more rigid protein domains revealed by fluorescence
      recovery after photobleaching experiments. Protein domains were observed to
      coalesce during this competitive adsorption process.

PMID- 21942230
TI  - Determination of emotional endophenotypes: a validation of the Affective
      Neuroscience Personality Scales and further perspectives.
AB  - The study of endophenotypes, notably with configured self-reports, represents a
      promising research pathway to overcome the limits of a syndromal approach of
      psychiatric diseases. The Affective Neuroscience Personality Scales (ANPS) is a
      self-report questionnaire, based on neuroethological considerations, that could
      help to assess emotional endophenotypes related to the activity in 6 core
      cerebral emotional systems (FEAR, ANGER, SADNESS, CARING, PLAYFULNESS, SEEKING).
      We further investigated its psychometric properties among 830 young adults and
      showed that they were satisfactory. As participants also completed several other
      self-reports that shared potential traits with the ANPS, we offer new validity
      evidence based on relations to other variables. We also provide additional
      evidence to consider that the ANPS scores can be validly interpreted for the
      characterization of emotional endophenotypes involved in a variety of psychiatric
      disorders. On the grounds of present results, of previous clinical studies, as
      well as some preliminary neuroimaging findings, we discuss new steps in the ANPS
      validation.

PMID- 21942229
TI  - Portability of a screener for pediatric bipolar disorder to a diverse setting.
AB  - Robust screening measures that perform well in different populations could help
      improve the accuracy of diagnosis of pediatric bipolar disorder. Changes in
      sampling could influence the performance of items and potentially influence total
      scores enough to alter the predictive utility of scores. Additionally, creating a
      brief version of a measure by extracting items from a longer scale might cause
      differential functioning due to context effects. The authors of current study
      examined both sampling and context effects of a brief measure of pediatric mania.
      Caregivers of 813 youths completed the parent-reported version of the General
      Behavior Inventory (PGBI) at an academic medical center sample enriched for mood
      disorders. Caregivers of 481 youths completed the PGBI at a community mental
      health center. Caregivers of 799 youths completed 10 items extracted from the
      PGBI at a community setting. Caregivers of 159 youths completed both versions of
      the PGBI and a semistructured diagnostic interview. Differential item functioning
      indicated that across samples some items functioned differently; however, total
      observed scores were similar across all levels of mania. Receiver operating
      characteristic analysis indicated that the 10 extracted items discriminated
      bipolar disorder from nonbipolar behavior as well as when the items were embedded
      within the full measure. Findings suggest that the extracted items perform
      similarly to the embedded items in the community setting. Measurement properties
      appear sufficiently robust across settings to support clinical applications.

PMID- 21942232
TI  - The Hispanic Stress Inventory--Adolescent Version: a culturally informed
      psychosocial assessment.
AB  - A 2-phase study was conducted to develop a culturally informed measure of
      psychosocial stress for adolescents: the Hispanic Stress Inventory--Adolescent
      Version (HSI-A). Phase 1 involved item development through the collection of open
      ended focus group interview data (n = 170) from a heterogeneous sample of
      Hispanic youths residing in the southwest and northeast United States. In Phase
      2, we examined the psychometric properties of the HSI-A (n = 1,651), which
      involved the use of factor analytic procedures to determine the underlying scale
      structure of the HSI-A for foreign-born and U.S.-born participants in an
      aggregated analytic approach. An 8-factor solution was established, with factors
      that include Family Economic Stress, Acculturation-Gap Stress, Culture and
      Educational Stress, Immigration-Related Stress, Discrimination Stress, Family
      Immigration Stress, Community and Gang-Related Stress, and Family and Drug
      Related Stress. Concurrent, related validity estimates were calculated to
      determine relations between HSI-A and other measures of child psychopathology and
      behavioral and emotional disturbances. HSI-A total stress appraisal scores were
      significantly correlated with both the Children's Depression Inventory and the
      Youth Self Report (p < .001). Reliability estimates for the HSI-A were conducted,
      and they yielded high reliability coefficients for most factor subscales, with
      the HSI-A total stress appraisal score reliability alpha at .92.

PMID- 21942233
TI  - Some supplementary methods for the analysis of the RBANS.
AB  - Supplementary methods for the analysis of the Repeatable Battery for the
      Assessment of Neuropsychological Status are made available, including (a)
      quantifying the number of abnormally low Index scores and abnormally large
      differences exhibited by a case and accompanying this with estimates of the
      percentages of the normative population expected to exhibit at least this number
      of low scores and large differences, (b) estimating the overall abnormality of a
      case's Index score profile using the Mahalanobis Distance Index (MDI), (c)
      reporting confidence limits on differences between a case's Index scores, and (d)
      offering the option of applying a sequential Bonferroni correction when testing
      for reliable differences. With the exception of the MDI, all the methods can be
      obtained using the formulas and tables provided in this article. However, for the
      convenience of clinicians, and to reduce the possibility of clerical error, the
      methods have also been implemented in a computer program. More importantly, the
      program allows the methods to be applied when only a subset of the Indexes is
      available. The program can be downloaded from
      www.abdn.ac.uk/~psy086/dept/RBANS_Supplementary_Analysis.htm

PMID- 21942234
TI  - Comparison of fracture strength of endocrowns and glass fiber post-retained
      conventional crowns.
AB  - The aim of this in vitro study was to compare the fracture strength of full
      ceramic crowns using two techniques-indirect conventional crowns retained by
      glass fiber posts, and endocrowns with an "anchorage" in the pulp chamber-and
      analyze the failure mode. For this purpose, 20 healthy mandibular molars were
      divided into two groups (n=10): GroupGC contained teeth with indirect
      conventional crowns, filling cores, and glass fiber posts; Group GE contained
      teeth with restorations of the endocrown type. Teeth were endodontically treated
      and prepared for ceramic restorations fabricated by the injection technique(IPS
      e.max Press, Ivoclar-Vivadent), forming the GC and GE groups. Specimens were
      mount-ed in a universal test machine (EMIC) and were submitted to an oblique
      compression load, at an angle of 135 degrees to the long axis of the tooth, until
      failure. Statistical evaluation performed by the Mann-Whitney nonparametric test
      showed significant differences between the two groups (p=0.002), with Group GE
      shown to be more resistant to compressive forces than Group GC. The pre-dominant
      failure pattern in both groups was fracture of the tooth on the side of force
      application and/or consequent displacement of the restoration on the opposite
      side.

PMID- 21942236
TI  - Data comparison between two dental spectrophotometers.
AB  - OBJECTIVES: The objective of this study was to clinically test whether the data
      from two different spectrophotometers, based on spot and surface measurements,
      can be compared. METHODS: Under standardized clinical conditions two devices
      (Vita Easyshade and Spectro Shade-Micro) were used to record the color of three
      areas (cervical, middle, and incisal) per tooth for three upper maxillary
      anterior teeth in 102 participants. Each position was measured three times to
      attain an average for the CIE L*a*b* coordinates and to attain the corresponding
      Vita Classical shade tab integrated in the software of both devices. Vita tabs
      were also described as L*a*b* values using earlier published translations so that
      color differences (DeltaE) could be calculated between them. RESULTS: The
      regression analysis between the two devices showed that the independent
      correlation coefficients of the L*a*b* values are low. Yet when the suggested
      shade codes are compared with Vita colors instead of L*a*b*, 40% of the cases
      were equal and 51% were clinically acceptable. SIGNIFICANCE: According to this
      study the two devices do not give a comparable shade selection output, and thus
      the exchange of L*a*b* values between the two spectrophotometers cannot be
      recommended.

PMID- 21942235
TI  - Randomized clinical trial of four adhesion strategies: 18-month results.
AB  - STATEMENT OF THE PROBLEM: With Institutional Review Board approval, 39 patients
      who needed restoration of noncarious cervical lesions (NCCLs) were enrolled in
      this study. A total of 125 NCCLs were selected and randomly assigned to four
      groups: 1) a three-step etch-and-rinse adhesive, Adper Scotchbond Multi-Purpose
      (MP, 3M ESPE, St Paul, MN, USA); 2) a two-step etch-and-rinse adhesive, Adper
      Single Bond Plus (SB, 3M ESPE); 3) a two-step self-etch adhesive, Adper
      Scotchbond SE (SE, 3M ESPE); and 4) a one-step self-etch adhesive, Adper Easy
      Bond (EB, 3M ESPE). A nanofilled composite resin was used for all restorations.
      Restorations were evaluated at six months and 18 months using modified U.S.
      Public Health Service (USPHS) parameters. RESULTS: At six months after initial
      placement, 107 restorations (85.6% recall rate) were evaluated. At 18 months, 94
      restorations (75.2% recall rate) were available for evaluation. The 6 mo/18 mo
      overall retention rates (%) were 100/90.9 for MP; 100/91.7 for SB; 100/90.9 for
      SE; and 96.4/92.3 for EB with no statistical difference between any pair of
      groups at each recall. Sensitivity to air decreased significantly for all
      adhesives from the preoperative to the postoperative stage and was stable
      thereafter. Interfacial staining did not change statistically from baseline to
      six months; however, interfacial staining at the enamel margins was statistically
      worse at 18 months than at baseline for the two self-etch adhesives EB and SE.
      Marginal adaptation was statistically worse at 18 months compared with baseline
      only for EB. This tendency was already significant at the six-month recall.
      CONCLUSION: Although 18-month retention was similar for the different adhesion
      strategies, enamel marginal deficiencies were more prevalent for the self-etch
      adhesives.

PMID- 21942237
TI  - Effect of tooth surface preparation on the bonding of self-etching primer
      adhesives.
AB  - The aim of this study was to determine the bonding effectiveness of four self
      etching primer adhesives after various tooth preparation protocols. Enamel/dentin
      specimens were prepared from 84 permanent molars, divided into three enamel
      preparation groups (silicon carbide paper [SiC1; erbium, chromium:yttri-um,
      scandium, gallium, garnet [Er,Cr:YSGG] laser [EL] and diamond bur [DB]) and five
      dentin preparation groups (SiC, EL, DB, steel[SB], and ceramic burs [CBs]). In
      each group,specimens were equally divided into four sub-groups and were bonded
      using Clearfil SEBond (CSE, Kuraray), Xeno IV (XE, Dentsply),Tokuyama Bond Force
      (TK, Tokuyama) and Filtek Silorane System Adhesive (FS, 3MESPE), as well as a
      hybrid resin composite(Clearfil Majesty Esthetic, Kuraray) for CSE,XE, and TK,
      and Filtek Posterior Restorative(3M ESPE) for FS). After 24 hours of water
      storage at 370C, microshear bond strength(iSBS) testing was carried out. Data
      were analyzed using analysis of variance (ANOVA)-Tukey test at a=0.05 and bond
      failure modes assessed. Representative debonded specimens were prepared and
      examined under the scanning electron microscope (SEM). All adhesives exhibited no
      significant differences in 1SBS on enamel and dentin under the clinical cavity
      preparation protocols, except for TK on den-tin. SEM revealed areas of altered
      subsurface enamel/dentin following EL ablation.

PMID- 21942238
TI  - Long-term nanoleakage depth and pattern of cervical restorations bonded with
      different adhesives.
AB  - PURPOSE: This study investigated the effect of water storage on nanoleakage depth
      and the pattern of cervical cavities bonded with different adhesives. METHODS:
      For nanoleakage depth evaluation, standardized cervical cavities (2 mm in
      diameter) were prepared on the buccal and lingual surfaces of 36 intact human
      premolars. Specimens were divided into three groups (n=12) according to the three
      adhesive systems used: an etch-and-rinse adhesive (SBMP, Adper Scotchbond Multi
      Purpose, 3M ESPE) and two single-step self-etch adhesives; one was mild and
      acetone based (IB-iBond, Kulzer), while the other was strong water based (PL,
      Adper Prompt L-Pop, 3M ESPE). All cavities were restored using Filtek Z250 (3M
      ESPE) resin composite. For each adhesive, specimens (n=12 with 24 restored
      cavities) were subdivided into three subgroups (n=4 with eight cavities)
      according to the storage period before examination (24 hours, three or six
      months). Another duplicate of teeth was prepared in the same way for nanoleakage
      pattern evaluation. After storage, the specimens were placed in 50%W/V silver
      nitrate solution for 24 hours and immersed in a photo-developing solution for
      eight hours. Thereafter, the specimens were sectioned buccolingually, polished,
      and examined by scanning electron microscopy. For nanoleakage pattern, specimens
      were treated in the same way as for nanoleakage depth except that they were
      additionally immersed in 10% EDTA for five seconds after polishing. Silver
      penetration percentage was calculated to the total length of the tooth
      restoration interface. Data were analyzed with two-way analysis of variance,
      Kruskal-Wallis, and post hoc tests. RESULTS: After 24 hours, the least amount of
      nanoleakage depth was recorded for IB, while the highest was recorded for PL. For
      stored specimens, there was no significant difference among the nanoleakage
      depths of all adhesives. The tested adhesives recorded different nanoleakage
      patterns; however, there was an increase in the intensity and continuity of
      silver deposition by time. CONCLUSIONS: After 24 hours, the nanoleakage
      depth/pattern varied with the type of adhesive used; however, after water
      storage, all adhesives performed equally.

PMID- 21942239
TI  - Influence of the curing mode on fluoride ion release of self-adhesive resin
      luting cements in water or during pH-cycling regimen.
AB  - This study evaluated the effects of curing modes and storage conditions on
      fluoride release of resin cements. In phase 1, the cumulative fluoride release
      rate from samples of the resin cements (Panavia F 2.0, RelyX Unicem, MaxCem, and
      BisCem) was quantified after 15 days storage in water (n=4). In phase 2, the
      fluoride release profiles from the same materials were analyzed during pH cycling
      (n=4). In this second phase, fluoride was measured at specific times (one, two,
      three, five, eight, and 15 days). Disk-shaped specimens were prepared (10 mm *
      0.5 mm), and the materials were either light activated or allowed to
      autopolymerize. For both phases, the fluoride release was measured using a
      fluoride ion-specific electrode. The fluoride release in water was not affected
      by the curing mode of RelyX Unicem and Maxcem resin cements. Panavia F. 2.0 and
      BisCem resin cements, either light cured or autopolymerized modes, released
      higher amounts of fluoride in water than the other self-adhesive cements. In
      phase 2, the concentration of fluoride released decreased from the first day of
      pH cycling until the 15th day for all resin cements, for both curing modes,
      regardless of the storage solution used (demineralizing/remineralizing). The
      fluoride release rate during pH cycling by Panavia F 2.0 and MaxCem was not
      affected by the curing mode. The effect of the curing mode on fluoride ion
      release in water or during pH cycling was product dependent.

PMID- 21942240
TI  - Effect of resin cement system and root region on the push-out bond strength of a
      translucent fiber post.
AB  - OBJECTIVES: This study evaluated the bond strength of luting systems for bonding
      glass fiber posts to root canal dentin. The hypothesis tested was that there are
      no differences in bond strength of glass fiber posts luted with different cement
      systems. METHODS: Forty bovine incisors were randomly assigned to five different
      resin cement groups (n=8). After endodontic treatment and crown removal,
      translucent glass fiber posts were bonded into the root canal using five
      different luting protocols (self-cured cement and etch-and-rinse adhesive system;
      dual-cured cement and etch-and-rinse adhesive system; self-cured cement and self
      etch adhesive system; dual-cured cement and self-etch adhesive system; and dual
      cured self-adhesive cement). Push-out bond strength was evaluated at three
      different radicular levels: cervical, middle, and apical. The interface between
      resinous cement and the post was observed using a stereoscopic microscope.
      RESULTS: Analysis of variance showed a statistically significant difference among
      the cements (p<0.05) and the root canal thirds (p<0.05). The self-adhesive
      resinous cement had lower values of retention. CONCLUSIONS: The resin cements
      used with etch-and-rinse and self-etch adhesive systems seem to be adequate for
      glass fiber post cementation.

PMID- 21942241
TI  - Reparability of aged silorane with methacrylate-based resin composite: micro
      shear bond strength and scanning electron microscopy evaluation.
AB  - OBJECTIVES: To evaluate the compatibility between aged siloranes and methacrylate
      based composites by simulating a common repair-technique. METHODS: Twenty
      substrates were constructed using silorane (Filtek Silorane, 3M ESPE) and
      methacrylate composites (Filtek Supreme XT, 3M ESPE). Substrates were aged in
      0.9% NaCl solution at 37 degrees C for 72 hours. Silorane build-ups were
      constructed on silorane substrates without any intermediate layer (IL).
      Methacrylate build-ups were constructed on silorane substrates without any IL,
      with a methacrylate IL (Heliobond, Ivoclar Vivadent), or with a phosphate
      methacrylate IL (Silorane System Adhesive Bond, 3M ESPE). Methacrylate build-ups
      were also constructed on methacrylate substrates without any IL. The micro-shear
      bond strength test was carried out after thermocycling. Bond strength data were
      statistically analyzed using analysis of variance and Tukey post hoc tests.
      Failure modes were assessed by means of scanning electron microscopy
      observations. RESULTS: The silorane-methacrylate group without any IL showed the
      lowest bond strength values (0.4 +/- 0.1 MPa). The use of a methacrylate-based IL
      (1.6 +/- 1.7 MPa) led to a slight increase in bond strength, whereas the use of
      phosphate-methacrylate IL (9.1 +/- 5.4 MPa) significantly increased bond
      strength. There was no statistically significant difference in bond strength
      between silorane-silorane (7.9 +/- 3.6 MPa) and methacrylate-methacrylate (9.5 +/
      4.1 MPa) groups without any IL.

PMID- 21942243
TI  - A call to arms: what you can do for computational drug discovery.

PMID- 21942242
TI  - Association of GSTT1 polymorphism with acute myeloid leukemia risk is dependent
      on smoking status.
AB  - Genetic polymorphisms in drug-metabolizing, DNA repair and multidrug resistance
      genes affect the risks for many cancers. We analyzed 21 polymorphisms in 17 genes
      in these pathways to evaluate their association with the risk of acute myeloid
      leukemia (AML) and to examine whether smoking modifies these associations in a
      population-based study in Korea (415 cases, 1700 controls). We found marginal
      associations between the risk of AML and CYP1A1 1188, and XRCC1 194, ERCC1 IVS5 +
      33 and WRN 787 polymorphisms. However, when we performed the analysis according
      to smoking exposure, we found a stronger association for ERCC1 only in the non
      smoking population (odds ratio [OR] = 0.74; 95% confidence interval [CI] = 0.60
      0.91, p = 0.004), while we found the GSTT1-null genotype to be associated with an
      increased risk of AML in ever-smokers (OR = 1.51; 95% CI = 1.06-2.15, p = 0.02).
      These results indicate that ERCC1 and GSTT1-null polymorphisms may have an effect
      on AML risk that is dependent on smoking exposure.

PMID- 21942244
TI  - Polarized IR spectra of the hydrogen bond in two different oxindole polymorphs
      with cyclic dimers in their lattices.
AB  - This article focuses on the problem of remarkably strong changes in the fine
      structure patterns of the nu(N-H) and nu(N-D) bands attributed to the hydrogen
      and deuterium bonds accompanying the phase transition, which occurs between two
      polymorphic forms of oxindole. The lattices of these two different crystals
      contain hydrogen-bonded cyclic dimers differ in their geometry parameters. The
      source of these differences in the polymorph spectral properties results from the
      geometry relations concerning the dimers constituting the lattice structural
      units. In the case of the "alpha" phase, the hydrogen bond lengths of the dimers
      differ by 0.18 A. This leads to the "off-resonance exciton coupling" weakly
      involving the dimer hydrogen bonds. For the "beta" phase, with practically
      symmetric dimers in the lattice, the spectra become typical for centrosymmetric
      hydrogen bond systems due to the full resonance of the proton or deuteron
      vibrations.

PMID- 21942245
TI  - Inhalation by design.

PMID- 21942246
TI  - Future inhaled drugs by virtual innovation: allergen delivery inhibitors.

PMID- 21942248
TI  - Interview with Peter Barnes.
AB  - Peter Barnes first started his career in respiratory research in the late 1970s
      following studies at the Universities of Oxford and Cambridge. He is currently
      Professor of Thoracic Medicine at the National Heart and Lung Institute, Head of
      Respiratory Medicine at Imperial College and Honorary Consultant Physician at the
      Royal Brompton Hospital. He speaks to Future Medicinal Chemistry about the
      molecular mechanisms currently under investigation by his group, and discusses
      his views on the latest therapeutic breakthroughs and the future of respiratory
      research.

PMID- 21942249
TI  - The paradox of respiratory R&D, and why 'inhaled-by-design' heralds a new dawn in
      asthma and chronic obstructive pulmonary disease treatments.

PMID- 21942250
TI  - Dual-pharmacology muscarinic antagonist and beta2 agonist molecules for the
      treatment of chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is one of the leading causes of
      death in the world today. Bronchodilators, particularly muscarinic antagonists
      and beta(2) agonists, are recommended for patients with moderate to severe COPD.
      Dual-pharmacology muscarinic antagonist- beta(2) agonist (MABA) molecules present
      an exciting new approach to the treatment of COPD by combining muscarinic
      antagonism and beta(2) agonism in a single entity. They have the potential to
      demonstrate additive or synergistic bronchodilation over either pharmacology
      alone. Due to this enticing prospect, several companies have now reported MABA
      discovery efforts through a conjugated/linked strategy with one candidate (GSK
      961081) demonstrating clinical proof of concept. Several MABA crystal forms have
      been identified, satisfying the requirements for inhaled dosing devices. There
      are significant challenges in designing MABAs, but the potential to achieve
      enhanced bronchoprotection in patients and facilitate 'triple therapy' makes this
      an extremely important and exciting area of pharmaceutical research.

PMID- 21942251
TI  - Third-generation long-acting beta2-adrenoceptor agonists: medicinal chemistry
      strategies employed in the identification of once-daily inhaled beta2
      adrenoceptor agonists.
AB  - Inhaled long-acting beta(2)-adrenoceptor agonists (LABAs) are highly effective
      bronchodilators in the treatment of asthma and chronic obstructive pulmonary
      disease. There is significant interest in the development of third-generation
      compounds that improve upon the marketed twice-daily LABAs salmeterol and
      formoterol. A principal advantage sought from the next generation is duration of
      action that supports once-daily dosing, although improved efficacy, faster onset,
      and increased therapeutic index are also frequently cited as objectives. Recent
      publications detailing medicinal chemistry programs directed at the discovery of
      third-generation LABAs illustrate a wide variety of strategies that have been
      successfully employed towards these goals. Some recent scientific advances in the
      understanding of inhaled bronchodilators are discussed and the reported medicinal
      chemistry strategies are reviewed in the context of these advances.

PMID- 21942252
TI  - Inhaled long-acting muscarinic antagonists in chronic obstructive pulmonary
      disease.
AB  - In 2002, the first long-acting muscarinic antagonist, tiotropium bromide
      (Spiriva((r))), was launched as a once-daily bronchodilating agent for the
      treatment of chronic obstructive pulmonary disease. Since then, there has been
      intense discovery research activity in this area and, currently, several
      alternative inhaled long-acting muscarinic antagonists are reported under
      clinical development by several pharmaceutical companies. This article will
      review the current inhaled development candidates, as well as literature reports
      of the most significant preclinical chemical series specifically designed as
      inhaled antimuscarinic agents.

PMID- 21942253
TI  - What is the potential for inhaled p38 inhibitors in the treatment of chronic
      obstructive pulmonary disease?
AB  - p38 has been an intensely studied therapeutic target in the pharmaceutical
      industry. With more than 20 compounds entering human trials, none have progressed
      beyond Phase II to the best of our knowledge. The transient efficacy seen in many
      of the Phase II trials has raised some concerns for the future potential of this
      target, particularly in rheumatoid arthritis. With this caveat, there is good
      evidence for p38 inhibition to be efficacious in chronic obstructive pulmonary
      disease and there are now several oral compounds currently in development for
      this disease, with encouraging data beginning to emerge. With an inhaled agent
      likely to improve the therapeutic window between efficacy and some of the common
      adverse events observed with oral p38 inhibitors it would seem a sensible
      approach to take for a disease of the lung. This review will highlight the
      potential for an inhaled p38 inhibitor in chronic obstructive pulmonary disease,
      as well as some of the design principles that are important to consider when
      developing an inhaled kinase inhibitor.

PMID- 21942254
TI  - Oligonucleotides: a multi-targeted approach for the treatment of respiratory
      diseases.
AB  - Reversing inflammatory lung disease remains the foremost challenge in treating
      respiratory diseases such as asthma and chronic obstructive pulmonary disease.
      Reducing (or modifying) the underlying inflammatory process with mono-target
      drugs has proven challenging. The era of designing 'one target for one disease'
      has evolved such that a growing body of evidence suggests a single drug that is
      capable of specifically targeting multiple targets and pathways would be better
      at arresting progression of these respiratory diseases and be an important
      advancement in current therapy. Oligonucleotide-based drugs represent an emerging
      class of drug candidates. Their properties, a broader range of targets over
      conventional small-molecule drugs and recent clinical proof-of-concept support
      their development as novel multi-targeting agents for the treatment of
      respiratory diseases.

PMID- 21942255
TI  - Inhaled antibiotics for gram-negative respiratory infections.
AB  - Several disease states create conditions that lead to opportunistic Gram-negative
      respiratory infections. Inhalation is the most direct and, until recently,
      underutilized means of antimicrobial drug targeting for respiratory tract
      infections. All approved antimicrobial agents for administration by inhalation
      are indicated for Pseudomonas aeruginosa infections in patients with cystic
      fibrosis. These inhaled therapies have directly contributed to a significant
      reduction in exacerbations and hospitalizations in this patient population over
      the last few decades. The relentless adaptation of pathogenic organisms to
      current treatment options demands that the pharmaceutical industry continue
      designing next-generation antimicrobial agents over 70 years after they were
      first introduced. Recent technological advances in inhalation devices and drug
      formulation techniques have broadened the scope of antimicrobial structural
      classes that can be investigated by inhalation; however, there is an urgent need
      to discover novel compounds with improved resistance profiles relative to those
      drugs that are already marketed.

PMID- 21942256
TI  - A perspective on synthetic and solid-form enablement of inhalation candidates.
AB  - The administration of compounds by a dry-powder inhaler presents significant
      challenges to the development and discovery chemist, owing to the stringent
      requirements placed upon the physical characteristics of the active
      pharmaceutical ingredient and the high complexity of the molecules concerned. The
      current state of synthetic chemistry technology is such that commercial syntheses
      of these compounds are demanding but achievable. While synthetic chemistry will
      remain a major component of the development of inhaled therapies, the main
      challenge facing practitioners in this area is the early identification of a
      suitable solid form. Further advances in the prediction of solid-form properties
      would significantly enable this field and may allow triage of molecules to be
      carried out at the design stage of projects.

PMID- 21942257
TI  - Novel cosuspension metered-dose inhalers for the combination therapy of chronic
      obstructive pulmonary disease and asthma.
AB  - Pressurized metered dose inhaler is the most common inhaled dosage form, ideally
      suited for delivering the highly potent compounds that medicinal chemists
      typically discover for respiratory therapeutic targets. The clinical benefit of
      combination therapy for asthma and chronic obstructive pulmonary disease has been
      well established, and many of the new discovery candidates are likely to be
      studied in the clinic as combination drugs even at early stages of development.
      We present a novel pressurized metered dose inhaler formulation approach to
      enable consistent aerosol performance of a respiratory therapeutic whether it is
      emitted from a single-, double- or triple-therapy product. This should enable
      rapid nonclinical and clinical assessment whether alone or in combination with
      other drugs, without the challenge of in vitro performance dissimilarity across
      product types.

PMID- 21942258
TI  - Consistency of dosing with a thermal aerosol generation system: in vitro and in
      vivo correlation.
AB  - Dosing consistency and reproducibility are presented for a novel pharmaceutical
      inhaler technology based on a thermal condensation process. Two different device
      platforms producing thermally generated aerosols have been created and used in
      clinical studies with a number of different drug compounds. Because this approach
      does not rely on energy from the user to disperse the aerosol particles, aerosol
      production is reliable, reproducible and virtually user independent following
      actuation. Pharmacokinetic data from multiple clinical studies show rapid
      absorption, dose proportionality, and concentration levels and variability
      similar to intravenous injection. In addition, products used in clinical trials
      show excellent subject consistency with the vast majority of devices delivering
      greater than 90% of the loaded dose and little drug exhaled.

PMID- 21942260
TI  - Pre-adolescent alcohol expectancies: critical shifts and associated maturational
      processes.
AB  - Children's alcohol expectancies shift in late childhood/early adolescence in ways
      thought to lead to increased risk for adolescent alcohol use. The precise nature
      of this shift and the maturational processes that may influence it remain to be
      clarified. To these ends, we compared expectancy endorsement by grade across four
      expectancy domains: positive, negative, arousal, and sedation, in a cross
      sectional sample of 3rd-6th grade children attending afterschool programs (n =
      299). Structural equation modeling (SEM) was then used to describe the
      relationships between expectancies and differences in (a) cognitive ability and
      concept formation, (b) risk-taking personality traits, and (c) social exposure or
      values regarding alcohol-related information. Results showed those children in
      higher grades endorsed significantly more positive, negative, and sedating
      expectancies for alcohol than their younger peers. Concept formation partially
      and fully mediated the relationships between grade and both positive and sedating
      expectancies, respectively, but not the relationship between grade and negative
      expectancies. Sensation seeking did not increase across grades in this sample,
      and the relationship between sensation seeking and positive expectancies was
      fully mediated by reported alcohol exposure and values. This study provides a
      basis for future exploration of developmental influences on alcohol expectancies,
      an understanding of which may be helpful in the design of prevention efforts
      targeting high-risk youth before adolescence.

PMID- 21942261
TI  - Exploratory studies in sensory reinforcement in male rats: effects of
      methamphetamine.
AB  - Understanding sensory reinforcement and the effects of stimulant drugs on sensory
      reinforcers is potentially important for understanding their influence on
      addiction processes. Experiment 1 explored the reinforcing properties of a visual
      stimulus and the effects of methamphetamine (METH) on responding maintained by a
      visual reinforcer (VRF) in male rats. Snout poke responses to the active
      alternative produced the VRF according to variable interval (VI) schedules of
      reinforcement, and responses to an inactive alternative had no programmed effect.
      Experiment 2 explored the effects of METH on choice between the VRF and a water
      reinforcer (H2ORF) using concurrent VI schedules in male rats. In Experiment 1,
      response-contingent onset of the VRF produced an increase in both the relative
      frequency and absolute rate of active responding. The rate of both active and
      inactive responding declined across the 40-min test sessions. METH did not
      differentially enhance active responding for the VRF. Instead, METH
      nondifferentially increased the rate of responding and attenuated the within
      session decline of responding. In Experiment 2, METH differentially increased the
      rate of responding for the VRF relative to the H2ORF. The results of these
      exploratory experiments indicate that the reinforcing effects of the VRF were
      weak and transient. In addition, METH treatment increased responding, and the
      specificity of the enhancement of METH was dependent upon the testing conditions.
      Potential explanations of these differences, such as novelty and reinforcer type,
      are discussed.

PMID- 21942263
TI  - Aldoxime dehydratase: probing the heme environment involved in the synthesis of
      the carbon-nitrogen triple bond.
AB  - Fourier transform infrared (FTIR) spectra, "light" minus "dark" difference FTIR
      spectra, and time-resolved step-scan (TRS(2)) FTIR spectra are reported for
      carbonmonoxy aldoxime dehydratase. Two C-O modes of heme at 1945 and 1964 cm(-1)
      have been identified and remained unchanged in H(2)O/D(2)O exchange and in the pH
      5.6-8.5 range, suggesting the presence of two conformations at the active site.
      The observed C-O frequencies are 5 and 16 cm(-1) lower and higher, respectively,
      than that obtained previously (Oinuma, K.-I.; et al. FEBS Lett.2004, 568, 44-48).
      We suggest that the strength of the Fe-His bond and the neutralization of the
      negatively charged propionate groups modulate the nu(Fe-CO)/nu(CO) back-bonding
      correlation. The "light" minus "dark" difference FTIR spectra indicate that the
      heme propionates are in both the protonated and deprotonated forms, and the
      photolyzed CO becomes trapped within a ligand docking site (nu(CO) = 2138 cm(
      1)). The TRS(2)-FTIR spectra show that the rate of recombination of CO to the
      heme is k(1945 cm(-1)) = 126 +/- 20 s(-1) and k(1964 cm(-1)) = 122 +/- 20 s(-1)
      at pH 5.6, and k(1945 cm(-1)) = 148 +/- 30 s(-1) and k(1964 cm(-1)) = 158 +/- 32
      s(-1) at pH 8.5. The rate of decay of the heme propionate vibrations is on a time
      scale coincident with the rate of rebinding, suggesting that there is a coupling
      between ligation dynamics in the distal heme environment and the environment
      sensed by the heme propionates. The implications of these results with respect to
      the proximal His-Fe heme environment including the propionates and the positively
      charged or proton-donating residues in the distal pocket which are crucial for
      the synthesis of nitriles are discussed.

PMID- 21942264
TI  - Nucleoside optimization for RNAi: a high-throughput platform.
AB  - The RNA induced silencing complex (RISC) contains at its core the endonuclease
      Argonaute (Ago) that allows for guide strand (GS)-mediated sequence-specific
      cleavage of the target mRNA. Functionalization of the sugar/phosphodiester
      backbone of the GS, which is in direct contact with Ago, presents a logical
      opportunity to affect RISC's activity. A systematic evaluation of modified
      nucleosides requires the synthesis of phosphoramidites corresponding to all four
      canonical bases (A, U, C, and G) and their sequential evaluation at each position
      along the 21-nucleotide-long GS. With the use of a platform approach, the
      sequential replacement of canonical bases with inosine greatly simplifies the
      problem and defines a new activity baseline toward which the corresponding sugar
      modified inosines are compared. This approach was validated using 2'-O-benzyl
      modification, which demonstrated that positions 5, 8, 15, and 19 can accommodate
      this large group. Application of this high-throughput methodology now allows for
      hypothesis-driven rational design of highly potent, immunologically silent and
      stable siRNAs suitable for therapeutic applications.

PMID- 21942262
TI  - Effects of varenicline and bupropion on cognitive processes among nicotine
      deprived smokers.
AB  - Nicotine deprivation is associated with craving, negative affect, and difficulty
      concentrating, which may contribute to subsequent relapse. Bupropion and
      varenicline are both effective treatments for smoking cessation, and evidence
      from clinical trials suggests that these treatments increase abstinence rates.
      However, the mechanism by which these medications reduce relapse remains unclear.
      Recent research has focused on cognitive processes, such as attention and working
      memory, which may predict relapse. In addition, there may also be sex differences
      in cognitive-related deficits during nicotine deprivation. The current sample
      consisted of 58 (22 females) daily smokers (at least 10 cigarettes per day)
      randomized to receive bupropion (300 mg/day), varenicline (2 mg/day), or placebo.
      After a 1-week run-up phase, participants completed a 9.5-hr laboratory session
      after overnight abstinence (CO verified). Participants completed measures of
      attention (Conners' Continuous Performance Task [CPT]), working memory (digits
      backward), and delay discounting. Measures of craving, withdrawal, and mood were
      also collected. Between-subjects ANCOVA models revealed that varenicline speeded
      reaction time, but reduced accuracy on the CPT compared with placebo. Sex
      moderated the effect of bupropion compared with placebo on working memory and
      delay discounting. Bupropion enhanced working memory for females but not males,
      and this pattern was reversed for delay discounting. The current data highlight
      the complex processes associated with nicotine deprivation and the need for
      future research to examine whether cognitive-related deficits are related to
      relapse. Identifying these mechanisms may help in the development of new
      pharmacological treatments.

PMID- 21942265
TI  - Evidence for direct binding between HetR from Anabaena sp. PCC 7120 and PatS-5.
AB  - HetR, master regulator of heterocyst differentiation in the filamentous
      cyanobacterium Anabaena sp. strain PCC 7120, stimulates heterocyst
      differentiation via transcriptional autoregulation and is negatively regulated by
      PatS and HetN, both of which contain the active pentapeptide RGSGR. However, the
      direct targets of PatS and HetN remain uncertain. Here, we report experimental
      evidence for direct binding between HetR and the C-terminal RGSGR pentapeptide,
      PatS-5. Strains with a hetR allele coding for conservative substitutions at
      residues 250-256 had altered patterns of heterocysts and, in some cases, reduced
      sensitivity to PatS-5. Cysteine scanning mutagenesis coupled with electron
      paramagnetic resonance (EPR) spectroscopy showed quenching of spin label motion
      at HetR amino acid 252 upon titration with PatS-5, indicating direct binding of
      PatS-5 to HetR. Gel shift assays indicated that PatS-5 disrupted binding of HetR
      to a 29 base pair inverted-repeat-containing DNA sequence upstream from hetP.
      Double electron-electron resonance EPR experiments confirmed that HetR existed as
      a dimer in solution and indicated that PatS-5 bound to HetR without disrupting
      the dimer form of HetR. Isothermal titration calorimetry experiments corroborated
      direct binding of PatS-5 to HetR with a K(d) of 227 nM and a 1:1 stoichiometry.
      Taken together, these results indicated that PatS-5 disrupted HetR binding to DNA
      through a direct HetR/PatS interaction. PatS-5 appeared to either bind in the
      vicinity of HetR amino acid L252 or, alternately, to bind in a remote site that
      leads to constrained motion of this amino acid via an allosteric effect or change
      in tertiary structure.

PMID- 21942271
TI  - Anion binding in the C3v-symmetric cavity of a protonated tripodal amine
      receptor: potentiometric and single crystal X-ray studies.
AB  - Tris(2-aminoethyl)amine (tren) based pentafluorophenyl-substituted tripodal L,
      tris[[(2,3,4,5,6-pentafluorobenzyl)amino]ethyl]amine receptor is synthesized in
      good yield and characterized by single crystal X-ray diffraction analysis.
      Detailed structural aspects of binding of different anionic guests toward L in
      its triprotonated form are examined thoroughly. Crystallographic results show
      binding of fluoride in the C(3v)-symmetric cavity of [H(3)L](3+) where spherical
      anion fluoride is in tricoordinated geometry via (N-H)(+)...F interaction in the
      complex [H(3)L(F)].[F](2).2H(2)O, (3). In the case of complexes
      [H(3)L(OTs)].[OTs](2), (4) and [H(3)L(OTs)].[NO(3)].[OTs], (5), tetrahedral p
      toluenesulphonate ion is engulfed in the cavity of [H(3)L](3+) via (N-H)(+)...O
      interactions. Interestingly, complex
      [(H(3)L)(2)(SiF(6))].[BF(4)](4).CH(3)OH.H(2)O, (6) shows encapsulation of
      octahedral hexafluorosilicate in the dimeric capsular assembly of two [H(3)L](3+)
      units, via a number of (N-H)(+)...F interactions. The kinetic parameters of L
      upon binding with different anions are evaluated using a potentiometric study in
      solution state. The potentiometric titration experiments in a polar protic
      methanol/water (1:1 v/v) binary solvent system show high affinity of the receptor
      toward more basic fluoride and acetate anions, with a lesser affinity for other
      inorganic anions (e.g., chloride, bromide, nitrate, sulfate, dihydrogenphosphate,
      and p-toluenesulphonate).

PMID- 21942272
TI  - Synthesis and characterization of carbon nanotube-polymer multilayer structures.
AB  - We develop lightweight, multilayer materials composed of alternating layers of
      poly dimethyl siloxane (PDMS) polymer and vertically aligned carbon nanotube
      (CNT) arrays, and characterize their mechanical response in compression. The CNT
      arrays used in the assembly are synthesized with graded mechanical properties
      along their thickness, and their use enables the creation of multilayer
      structures with low density (0.12-0.28 g/cm(3)). We test the mechanical response
      of structures composed of different numbers of CNT layers partially embedded in
      PDMS polymer, under quasi-static and dynamic loading. The resulting materials
      exhibit a hierarchical, fibrous structure with unique mechanical properties: They
      can sustain large compressive deformations (up to ~0.8 strain) with a nearly
      complete recovery and present strain localization in selected sections of the
      materials. Energy absorption, as determined by the hysteresis observed in stress
      strain curves, is found to be at least 3 orders of magnitude larger than that of
      natural and synthetic cellular materials of comparable density. Conductive bucky
      paper is included within the polymer interlayers. This allows the measurement of
      resistance variation as a function of applied stress, showing strong correlation
      with the observed strain localization in compression.

PMID- 21942273
TI  - Asymmetric catalytic cycloetherification mediated by bifunctional
      organocatalysts.
AB  - Oxacyclic structures such as tetrahydrofuran (THF) rings are commonly found in
      many bioactive compounds, and this has led to several efforts toward their
      stereoselective syntheses. However, the process of catalytic asymmetric
      cycloetherification for their straightforward synthesis has remained a challenge.
      In this study, we demonstrate a novel asymmetric synthesis method for THF via the
      catalytic cycloetherification of epsilon-hydroxy-alpha,beta-unsaturated ketones
      mediated by cinchona-alkaloid-thiourea-based bifunctional organocatalysts. This
      catalytic process represents a highly practical cycloetherification method that
      provides excellent enantioselectivities, even with low catalyst loadings at
      ambient temperature.

PMID- 21942274
TI  - Protein-based SERS technology monitoring the chemical reactivity on an alpha
      synuclein-mediated two-dimensional array of gold nanoparticles.
AB  - The enhancement of weak Raman signals has been challenged to obtain high-quality
      signals of surface-enhanced Raman scattering (SERS). By employing the Parkinson's
      disease-related protein of alpha-synuclein, we introduce SERS-active gold
      nanoparticles (AuNPs) individually isolated with an ultrathin alpha-synuclein
      shell and their 2-D array into a tightly packed monolayer on a glass support,
      which permits a quantitative SERS measurement of phthalocyanine tetrasulfonate
      (PcTS), a chemical ligand of the pathological protein. Subsequently, the PcTS
      bound SERS substrate was also shown to be capable of discriminating two
      biologically important metal ions of iron and copper by detecting copper ion to
      the sub-ppm level in a highly selective manner via the in situ chemical reaction
      of metal chelation to PcTS. The strategy of using the protein-based 2-D AuNP SERS
      platform, therefore, could be further developed into a custom-made protein-based
      biosensor system for the detection of not only specific chemical/biological
      ligands of the immobilized coat proteins but also their biochemical reactivities.

PMID- 21942275
TI  - Association of airway inflammation with asthma control level evaluated by the
      asthma control test.
AB  - BACKGROUND: The association between airway inflammation and asthma control level
      is not clear at present. OBJECTIVE: This study aimed to explore the association
      by using induced sputum and asthma control status as determined by the Asthma
      Control Test (ACT). We also evaluated the association between the scores for each
      ACT question item and eosinophilic or neutrophilic airway inflammation. METHODS:
      The ACT and sputum induction were performed at the same time. Associations
      between total scores or scores for each question item and sputum eosinophil or
      neutrophil counts were examined. The study was approved by an Institutional
      Review Board. RESULTS: Of the 101 patients with chronic asthma enrolled, data
      from 98 (controlled n = 66, uncontrolled n = 32) were analyzed [60.0 years (43.0
      68.0) M:F = 34:64]. Current control status determined by the ACT was not
      significantly associated with eosinophilic or neutrophilic inflammation. Among
      the ACT items, only nocturnal symptoms were associated with sputum eosinophils:
      patients with a positive answer to the question had significantly higher
      eosinophil counts than patients with a negative answer [5.4 (2.2-17.6) versus 2.1
      (0.7-7.3), respectively, p = 0.08]. Furthermore, significant correlation was
      found between eosinophil counts and the scores for nocturnal symptoms (rs = 
      0.218 p = 0.031). On the other hand, patients with rescue use of a short-acting
      b2-agonist (SABA) had significantly higher sputum neutrophil counts than non-SABA
      users [73.4 (52.8-83.4) versus 61.0 (36.3-74.8), respectively, p = 0.031]. The
      other ACT items were not significantly associated with sputum neutrophils. The
      neutrophil count correlated significantly with the frequency of rescue SABA use
      (rs = -0.218 p = 0.031). CONCLUSIONS: Asthma control level evaluated by the ACT
      was not associated with airway eosinophilic or neutrophilic inflammation.
      However, the frequency of nocturnal symptoms was associated with sputum
      eosinophilia, and the frequency of rescue SABA use was associated with sputum
      neutrophilia.

PMID- 21942276
TI  - Copper-doped inverted core/shell nanocrystals with "permanent" optically active
      holes.
AB  - We have developed a new class of colloidal nanocrystals composed of Cu-doped ZnSe
      cores overcoated with CdSe shells. Via spectroscopic and magneto-optical studies,
      we conclusively demonstrate that Cu impurities represent paramagnetic +2 species
      and serve as a source of permanent optically active holes. This implies that the
      Fermi level is located below the Cu(2+)/Cu(1+) state, that is, in the lower half
      of the forbidden gap, which is a signature of a p-doped material. It further
      suggests that the activation of optical emission due to the Cu level requires
      injection of only an electron without a need for a valence-band hole. This
      peculiar electron-only emission mechanism is confirmed by experiments in which
      the titration of the nanocrystals with hole-withdrawing molecules leads to
      enhancement of Cu-related photoluminescence while simultaneously suppressing the
      intrinsic, band-edge exciton emission. In addition to containing permanent
      optically active holes, these newly developed materials show unprecedented
      emission tunability from near-infrared (1.2 eV) to the blue (3.1 eV) and reduced
      losses from reabsorption due to a large Stokes shift (up to 0.7 eV). These
      properties make them very attractive for applications in light-emission and
      lasing technologies and especially for the realization of novel device concepts
      such as "zero-threshold" optical gain.

PMID- 21942277
TI  - Simultaneous determination of orysastrobin and its isomers in rice using HPLC-UV
      and LC-MS/MS.
AB  - Orysastrobin is a new strobilurin-type fungicide to control leaf and panicle
      blast and sheath blight in rice. An analytical method was developed to determine
      the residues of orysastrobin and its two isomers, the main metabolite F001 and
      the major impurity F033, in hulled rice by the use of high-performance liquid
      chromatography with ultraviolet photometry (HPLC-UV) and liquid chromatography
      with tandem mass spectrometry (LC-MS/MS). All compounds were extracted with
      acetone from hulled rice samples. The extract was diluted with saline water, and
      an extraction step using dichloromethane/n-hexane partition was used to recover
      analytes from the aqueous phase. An n-hexane/acetonitrile partition and Florisil
      column chromatography were employed to further remove interfering coextractives
      prior to instrumental analysis. An octadecylsilyl column was successfully applied
      to identify orysastrobin and its isomers in sample extracts. Net recovery rates
      of orysastrobin, F001, and F033 from fortified samples ranged from 80.6 to 114.8%
      using HPLC-UV and LC-MS/MS. Relative standard deviations for the analytical
      methods were all <20%, and the quantification limits of the method were in the
      0.002-0.02 mg/kg range. The proposed methods were reproducible and sufficiently
      accurate to evaluate the terminal residue of orysastrobin and its isomers in
      rice.

PMID- 21942278
TI  - Effect of lyophilized amniotic membrane on the development of adhesions and
      fibrosis after extraocular muscle surgery in rabbits.
AB  - PURPOSE: To histopathologically evaluate the influence of lyophilized human
      amniotic membrane transplant on the development of postoperative adhesions and
      fibrosis after extraocular muscle surgery. METHODS: Ten albino rabbits were used.
      The superior rectus muscle was resected 4 mm in both eyes. In right eyes, the
      superior rectus muscle was wrapped with lyophilized (air-dried, freeze-dried)
      human amniotic membrane (group AM). In left eyes, the superior rectus muscle was
      not wrapped with amniotic membrane, and served as a control group (group C). The
      rabbits were sacrificed and the eyes were enucleated 6 weeks after surgery to
      perform histopathological examination. RESULTS: Two rabbits died 1 week after
      surgery and were excluded. Histopathological evaluation of both eyes of the
      remaining 8 rabbits was done. The amniotic membrane was not seen in all eyes. On
      comparing eye pairs of each rabbit, right eyes showed significantly less
      conjunctival inflammation (p = 0.034), but insignificantly less foreign body
      inflammation (p = 0.625), adhesions between sclera and muscle (p = 0.206), muscle
      fibrosis (p = 1.000), and conjunctival hyperemia (p = 0.059) as compared to left
      eyes. CONCLUSIONS: Lyophilized amniotic membrane insignificantly reduces
      postoperative adhesions and fibrosis, when used to wrap the operated upon
      extraocular muscles, limiting the benefit of this membrane in strabismus surgery.

PMID- 21942279
TI  - Life-span development of self-esteem and its effects on important life outcomes.
AB  - We examined the life-span development of self-esteem and tested whether self
      esteem influences the development of important life outcomes, including
      relationship satisfaction, job satisfaction, occupational status, salary,
      positive and negative affect, depression, and physical health. Data came from the
      Longitudinal Study of Generations. Analyses were based on 5 assessments across a
      12-year period of a sample of 1,824 individuals ages 16 to 97 years. First,
      growth curve analyses indicated that self-esteem increases from adolescence to
      middle adulthood, reaches a peak at about age 50 years, and then decreases in old
      age. Second, cross-lagged regression analyses indicated that self-esteem is best
      modeled as a cause rather than a consequence of life outcomes. Third, growth
      curve analyses, with self-esteem as a time-varying covariate, suggested that self
      esteem has medium-sized effects on life-span trajectories of affect and
      depression, small to medium-sized effects on trajectories of relationship and job
      satisfaction, a very small effect on the trajectory of health, and no effect on
      the trajectory of occupational status. These findings replicated across 4
      generations of participants--children, parents, grandparents, and their great
      grandparents. Together, the results suggest that self-esteem has a significant
      prospective impact on real-world life experiences and that high and low self
      esteem are not mere epiphenomena of success and failure in important life
      domains.

PMID- 21942280
TI  - Prosociality: the contribution of traits, values, and self-efficacy beliefs.
AB  - The present study examined how agreeableness, self-transcendence values, and
      empathic self-efficacy beliefs predict individuals' tendencies to engage in
      prosocial behavior (i.e., prosociality) across time. Participants were 340 young
      adults, 190 women and 150 men, age approximately 21 years at Time 1 and 25 years
      at Time 2. Measures of agreeableness, self-transcendence, empathic self-efficacy
      beliefs, and prosociality were collected at 2 time points. The findings
      corroborated the posited paths of relations, with agreeableness directly
      predicting self-transcendence and indirectly predicting empathic self-efficacy
      beliefs and prosociality. Self-transcendence mediated the relation between
      agreeableness and empathic self-efficacy beliefs. Empathic self-efficacy beliefs
      mediated the relation of agreeableness and self-transcendence to prosociality.
      Finally, earlier prosociality predicted agreeableness and empathic self-efficacy
      beliefs assessed at Time 2. The posited conceptual model accounted for a
      significant portion of variance in prosociality and provides guidance to
      interventions aimed at promoting prosociality.

PMID- 21942281
TI  - Stability test for amorphous materials in humidity controlled 96-well plates by
      near-infrared spectroscopy.
AB  - The purpose of this research is to apply near infrared spectrometry (NIR) with
      chemoinformetrics to predict the change of crystalline properties of indomethacin
      (IMC) amorphous under various levels of relative humidity storage conditions.
      Stability test for amorphous and meta-stable polymorphic forms was performed in
      humidity controlled the modified 96-well quartz plates containing various kinds
      of saturated salt solutions (0-100% of relative humidity (RH)) by NIR
      spectroscopy. Amorphous form was obtained melt product to pour into liquid
      nitrogen and after then ground. Samples were stored at 25 degrees C in the 6-well
      plates at various levels of RH. The spectra of the powder samples were measured
      by the reflectance FT-NIR spectrometer. The second derivative spectra of form
      alpha showed specific absorption peaks at 4980, 6036, 7296 and 8616 cm-1 and that
      of form gamma showed those at 5020, 5028, 7344, 7428 and 8436 cm-1. After storage
      at less than 50% RH, the peak intensities at 5020, 5028, 7344, 7428 and 8436 cm-1
      of the amorphous solid increased with increasing of storage time. However, the
      peak intensity at 4980, 6036 and 7296 cm-1 increased at more than 50% RH Please
      check and confirm the edit. The results suggested that at lower humidity, the IMC
      amorphous solid transformed into form gamma, but it transformed into form alpha
      at more than high humidity. It is possible that crystalline stability of the
      pharmaceutical preparations could be predicted by using humidity controlled 96
      well plates and reflectance NIR-chemoinformetric methods.

PMID- 21942282
TI  - Molecular-dynamics-based study of the collisions of hyperthermal atomic oxygen
      with graphene using the ReaxFF reactive force field.
AB  - In this work, we have investigated the hyperthermal collisions of atomic oxygens
      with graphene through molecular dynamics simulations using the ReaxFF reactive
      force field. First, following Paci et al. (J. Phys. Chem. A 2009, 113, 4677 -
      4685), 5-eV energetic collisions of atomic oxygen with a 24-atom pristine
      graphene sheet and a sheet with a single vacancy defect, both functionalized with
      oxygen atoms in the form of epoxides, were studied. We found that the removal of
      an O(2) molecule from the surface of the graphene sheet occurs predominantly
      through an Eley-Rideal-type reaction mechanism. Our results, in terms of the
      number of occurrences of various reactive events, compared well with those
      reported by Paci et al. Subsequently, energetic collisions of atomic oxygen with
      a 25-times-expanded pristine sheet were investigated. The steady-state oxygen
      coverage was found to be more than one atom per three surface carbon atoms. Under
      an oxygen impact, the graphene sheet was always found to buckle along its
      diagonal. In addition, the larger sheet exhibited trampoline-like behavior, as a
      result of which we observed a much larger number of inelastic scattering events
      than those reported by Paci et al. for the smaller system. Removal of O(2) from
      the larger sheet occurred strictly through an Eley-Rideal-type reaction.
      Investigation of the events leading to the breakup of a pristine unfunctionalized
      graphene sheet and the effects of the presence of a second layer beneath the
      graphene sheet in an AB arrangement was done through successive impacts with
      energetic oxygen atoms on the structures. Breakup of a graphene sheet was found
      to occur in two stages: epoxide formation, followed by the creation and growth of
      defects. Events leading to the breakup of a two-layer graphene stack included
      epoxide formation, transformation from an AB to an AA arrangement as a result of
      interlayer bonding, defect formation and expansion in the top layer, and finally
      erosion of the bottom layer. We observed that the breakup of the two-layer stack
      occurred through a sequential, layer-by-layer, erosion process.

PMID- 21942283
TI  - Photochemical activation of ruthenium(II)-pyridylamine complexes having a
      pyridine-N-oxide pendant toward oxygenation of organic substrates.
AB  - Ruthenium(II)-acetonitrile complexes having eta(3)-tris(2-pyridylmethyl)amine
      (TPA) with an uncoordinated pyridine ring and diimine such as 2,2'-bipyridine
      (bpy) and 2,2'-bipyrimidine (bpm), [Ru(II)(eta(3)-TPA)(diimine)(CH(3)CN)](2+),
      reacted with m-chloroperbenzoic acid to afford corresponding Ru(II)-acetonitrile
      complexes having an uncoordinated pyridine-N-oxide arm, [Ru(II)(eta(3)-TPA
      O)(diimine)(CH(3)CN)](2+), with retention of the coordination environment.
      Photoirradiation of the acetonitrile complexes having diimine and the eta(3)-TPA
      with the uncoordinated pyridine-N-oxide arm afforded a mixture of
      [Ru(II)(TPA)(diimine)](2+), intermediate-spin (S = 1) Ru(IV)-oxo complex with
      uncoordinated pyridine arm, and intermediate-spin Ru(IV)-oxo complex with
      uncoordinated pyridine-N-oxide arm. A Ru(II) complex bearing an oxygen-bound
      pyridine-N-oxide as a ligand and bpm as a diimine ligand was also obtained, and
      its crystal structure was determined by X-ray crystallography. Femtosecond laser
      flash photolysis of the isolated O-coordinated Ru(II)-pyridine-N-oxide complex
      has been investigated to reveal the photodynamics. The Ru(IV)-oxo complex with an
      uncoordinated pyridine moiety was alternatively prepared by reaction of the
      corresponding acetonitrile complex with 2,6-dichloropyridine-N-oxide (Cl(2)py-O)
      to identify the Ru(IV)-oxo species. The formation of Ru(IV)-oxo complexes was
      concluded to proceed via intermolecular oxygen atom transfer from the
      uncoordinated pyridine-N-oxide to a Ru(II) center on the basis of the results of
      the reaction with Cl(2)py-O and the concentration dependence of the consumption
      of the starting Ru(II) complexes having the uncoordinated pyridine-N-oxide
      moiety. Oxygenation reactions of organic substrates by [Ru(II)(eta(3)-TPA
      O)(diimine)(CH(3)CN)](2+) were examined under irradiation (at 420 +/- 5 nm) and
      showed selective allylic oxygenation of cyclohexene to give cyclohexen-1-ol and
      cyclohexen-1-one and cumene oxygenation to afford cumyl alcohol and acetophenone.

PMID- 21942284
TI  - Risk assessment in human immunodeficiency virus-associated acute myeloid
      leukemia.
AB  - CD4 count <=200*10(6) cells/L has been identified as a predictor of short
      survival in HIV-associated acute myeloid leukemia (HIV-AML), but karyotype, which
      is the best predictor of survival in AML, has not been evaluated in HIV-AML
      patients. A retrospective cohort of 31 patients was created from 9 local cases
      and 22 published cases. HIV-AML karyotypes were heterogeneous and were similar in
      distribution to those in HIV-negative AML. Among intensively treated patients,
      most achieved complete remission, but succumbed to infectious complications,
      mostly non-opportunistic, during consolidation therapy. Median survival for
      intensively-treated patients with CD4 counts <=200*10(6) cells/L was 8.5 months,
      compared to 48 months for those with >200*10(6) CD4 cells/L (p=0.03). In
      contrast, AML karyotype did not predict survival (p=0.43), albeit with small
      numbers in each karyotype group. Thus, CD4 count is a strong predictor of short
      survival in HIV-AML patients regardless of karyotype. Studies evaluating
      innovative strategies for infection prophylaxis and for improving immune
      reconstitution are needed.

PMID- 21942285
TI  - Antigenic drift in relapsed extramedullary multiple myeloma: plasma cells without
      CD38 expression.

PMID- 21942286
TI  - Microwave-based reaction screening: tandem retro-Diels-Alder/Diels-Alder
      cycloadditions of o-quinol dimers.
AB  - We have accomplished a parallel screen of cycloaddition partners for o-quinols
      utilizing a plate-based microwave system. Microwave irradiation improves the
      efficiency of retro-Diels-Alder/Diels-Alder cascades of o-quinol dimers which
      generally proceed in a diastereoselective fashion. Computational studies indicate
      that asynchronous transition states are favored in Diels-Alder cycloadditions of
      o-quinols. Subsequent biological evaluation of a collection of cycloadducts has
      identified an inhibitor of activator protein-1 (AP-1), an oncogenic transcription
      factor.

PMID- 21942287
TI  - Proximal marginal overhang of composite restorations in relation to placement
      technique of separation rings.
AB  - The aim was to investigate in vitro the marginal overhang in Class II composite
      restorations placed with various separation rings and placement techniques. A
      total of 180 Mesial-Occlusal [MO] preparations in artificial molar teeth were
      divided into nine groups (n=20). After placement of the sectional matrix, one of
      three ring systems was applied: Contact Matrix System (Danville Materials),
      Composi-Tight Gold (Garrison), and V-Ring (Triodent). In each group, rings were
      placed according to four different techniques (V-Ring placed with technique no. 2
      only): 1) occlusally of the wedge, 2) on back end of the wedge, 3) between
      adjacent tooth and wedge, and 4) between treated tooth and wedge.After
      application of the adhesive resin, preparations were restored with composite
      Clearfil AP-X (Kuraray) and polymerized in increments. After matrix removal,
      overhang was measured on a standardized digital macroscopic image in millimeters
      squared. For analysis, analysis of variance and Tukey B were used (p<0.05).For
      the Contact Matrix System and Composi-Tight Gold ring, the different placement
      techniques had a statistically significant effect on the amount of marginal
      overhang (p<0.031). The V-Ring resulted in the least marginal overhang
      (p<0.001).None of the placement techniques and separation rings could completely
      prevent marginal overhang, and the placement technique has a significant
      influence on its occurrence.

PMID- 21942288
TI  - In vitro evaluation of the effect of delaying toothbrushing with toothpaste on
      enamel microhardness subsequent to bleaching the teeth with 15% carbamide
      peroxide.
AB  - Changes in enamel surface microhardness as a result of bleaching with carbamide
      peroxide in various in vitro conditions have been reported. The present study
      evaluated the effect of oral hygiene procedures on enamel microhardness at three
      time intervals following bleaching with 15% carbamide peroxide. Although this was
      an in vitro study, the purpose was to address whether or not a patient's
      toothbrushing following at-home bleaching might affect surface changes in tooth
      enamel. Eighty enamel slabs were prepared from impacted human third molars that
      had been extracted surgically. Subsequent to placing the specimens in acrylic
      resin, their surfaces were smoothed, and they were randomly divided into four
      equal groups. The specimens were initially evaluated for microhardness by Vickers
      test. The bleaching procedure was carried out for 21 days for 6 hours daily. In
      each group, the surfaces of specimens were brushed with toothpaste immediately, 1
      hour, and 2 hours after bleaching except for the control group. The specimens
      were stored in artificial saliva. Enamel microhardness was again measured at the
      end of the bleaching period. Then the differences in enamel microhardness between
      the two periods were calculated. Data were analyzed with a nonparametric Kruskal
      Wallis test at a significance level of p<0.05. The differences in the
      microhardness values before and after intervention between the groups were not
      significant (p=0.59). Daily oral hygiene procedures either immediately or 1 or 2
      hours after daily bleaching procedures and exposing the specimens to artificial
      saliva during the study period produced no significant differences in enamel
      microhardness values.

PMID- 21942289
TI  - Treatment of invasive cervical resorption with sandwich technique using mineral
      trioxide aggregate: a case report.
AB  - This article presents two cases of large invasive cervical resorption (ICR) with
      maintenance of pulp vitality after treatment with mineral trioxide aggregate
      (MTA) in a sandwich technique.Invasive cervical resorption is a relatively
      uncommon but aggressive form of external resorption, primarily caused by dental
      trauma or injury of the cervical periodontal attachment. The resorptive process
      does not penetrate into the root canal, and the pulp is not involved in the first
      phase of the resorption. This feature differentiates external resorption from
      internal resorption. In most cases, invasive cervical resorption is found during
      routine radiographic or clinical examination. Different materials have been
      proposed for the treatment of external cervical resorption. Therapy can be
      effective when it 1) removes the etiological factors and 2) interrupts the
      progressive resorption mechanism.The key learning points of this article are the
      following: treatment strategy to arrest the cervical resorption process and to
      prevent further resorption without changing pulpal vitality and successful seal
      of invasive cervical resorption defect using MTA with a sandwich technique.

PMID- 21942294
TI  - Curcumin heals indomethacin-induced gastric ulceration by stimulation of
      angiogenesis and restitution of collagen fibers via VEGF and MMP-2 mediated
      signaling.
AB  - AIM: We examined the molecular mechanism of curcumin in a preventive and
      therapeutic model of indomethacin-induced gastric ulceration with regard to
      angiogenic processes. RESULTS: Disrupted blood vessels, reduced collagen
      matrices, and significant (60%) injury to mucosal cells were observed during
      ulceration. In addition, ulcerated tissues exhibited decreased matrix
      metalloproteinase (MMP)-2 and vascular endothelial growth factor (VEGF)
      expression in blood vessels. Interestingly, curcumin blocked ulceration by
      induction of collagenization and angiogenesis in gastric tissues via upregulation
      of MMP-2, membrane type (MT) 1-MMP, VEGF, and transforming growth factor (TGF)
      beta at protein and messenger ribonucleic acid (mRNA) levels. To examine the
      angiogenic properties of curcumin, we employed a chorioallantoic membrane model
      and Matrigel assay. During healing, curcumin promoted collagenization and
      angiogenesis as well as enhanced MMP-2 activity via positive MT1-MMP regulation
      and negative tissue inhibitor of metalloproteinase-2 regulation. INNOVATION: Our
      study demonstrates that curcumin-mediated healing is associated with increased
      MMP-2, TGF-beta, and VEGF expression and that it plays a pivotal role as an
      angiogenic modulator by stimulating vascular sprout formation and collagen fiber
      restoration in ulcerated tissues. CONCLUSION: We conclude that curcumin remodels
      gastric tissues by restoring the collagen architecture and accelerating
      angiogenesis.

PMID- 21942296
TI  - Photochemical synthesis of a water oxidation catalyst based on cobalt
      nanostructures.
AB  - New cobalt-based nanocomposites have been prepared by photoreduction of Co(2+)
      salts to generate cobalt nanoparticles deposited on carbon-based materials such
      as nanocyrstalline diamond and carbon felt. Spontaneous air oxidation converts
      the metal to Co(2)O(3) which has been tested as a water oxidation catalyst. This
      work demonstrates that the cobalt oxide nanostructures can be deposited on
      various carbon surfaces and can catalyze the four-electron oxidation of water to
      oxygen under anodic bias.

PMID- 21942297
TI  - Effects of ammonia on the structure of the oxygen-evolving complex in photosystem
      II as revealed by light-induced FTIR difference spectroscopy.
AB  - NH(3) is a structural analogue of substrate H(2)O and an inhibitor to the water
      oxidation reaction in photosystem II. To test whether or not NH(3) is able to
      replace substrate water molecules on the oxygen-evolving complex in photosystem
      II, we studied the effects of NH(3) on the high-frequency region (3750-3550 cm(
      1)) of the S(2)Q(A)(-)/S(1)Q(A) FTIR difference spectra (pH 7.5 at 250 K), where
      OH stretch modes of weak hydrogen-bonded active water molecules occur. Our
      results showed that NH(3) did not replace the active water molecule on the oxygen
      evolving complex that gave rise to the S(1) mode at ~3586 cm(-1) and the S(2)
      mode at ~3613 cm(-1) in the S(2)Q(A)(-)/S(1)Q(A) FTIR difference spectrum of
      PSII. In addition, our mid-frequency FTIR results showed a clear difference
      between pH 6.5 and 7.5 on the concentration dependence of the NH(4)Cl-induced
      upshift of the S(2) state carboxylate mode at 1365 cm(-1) in the S(2)Q(A)(
      )/S(1)Q(A) spectra of NH(4)Cl-treated PSII samples. Our results provided strong
      evidence that NH(3) induced this upshift in the spectra of NH(4)Cl-treated PSII
      samples at 250 K. Moreover, our low-frequency FTIR results showed that the Mn-O
      Mn cluster vibrational mode at 606 cm(-1) in the S(2)Q(A)(-)/S(1)Q(A) spectrum of
      the NaCl control PSII sample was diminished in those samples treated with
      NH(4)Cl. Our results suggest that NH(3) induced a significant alteration on the
      core structure of the Mn(4)CaO(5) cluster in PSII. The implication of our
      findings on the structure of the NH(3)-binding site on the OEC in PSII will be
      discussed.

PMID- 21942298
TI  - Using polymer conformation to control architecture in semiconducting
      polymer/viral capsid assemblies.
AB  - Cowpea chlorotic mottle virus is a single-stranded RNA plant virus with a
      diameter of 28 nm. The proteins comprising the capsid of this virus can be
      purified and reassembled either by themselves to form hollow structures or with
      polyanions such as double-stranded DNA or single-stranded RNA. Depending on pH
      and ionic strength, a diverse range of structures and shapes can form. The work
      presented here focuses on using these proteins to encapsulate a fluorescent
      polyanionic semiconducting polymer, MPS-PPV (poly-2-methoxy-5-propyloxy sulfonate
      phenylene vinlyene), in order to obtain optically active virus-like particles.
      After encapsulation, fluorescence from MPS-PPV shows two distinct peaks, which
      suggests the polymer may be in two conformations. A combination of TEM,
      fluorescence anisotropy, and sucrose gradient separation indicate that the blue
      peak arises from polymer encapsulated into spherical particles, while the redder
      peak corresponds to polymers contained in rod-like cages. Ionic strength during
      assembly can be used to tune the propensity to form rods or spheres. The results
      illustrate the synergy of hybrid synthetic/biological systems: polymer
      conformation drives the structure of this composite material, which in turn
      modifies the polymer optical properties. This synergy could be useful for the
      future development of synthetic/biological hybrid materials with designated
      functionality.

PMID- 21942299
TI  - Cubane-type Fe4S4 clusters with chiral thiolate ligation: formation by ligand
      substitution, detection of intermediates by 1H NMR, and solid state structures
      including spontaneous resolution upon crystallization.
AB  - Cubane-type clusters [Fe(4)S(4)(SR*)(4)](2-) containing chiral thiolate ligands
      with R* = CH(Me)Ph (1), CH(2)CH(Me)Et (2), and CH(2)CH(OH)CH(2)OH (3) have been
      prepared by ligand substitution in the reaction systems [Fe(4)S(4)(SEt)(4)]/R*SH
      (1-3, acetonitrile) and [Fe(4)S(4)Cl(4)](2-)/NaSR*(3, Me(2)SO). Reactions with
      successive equivalents of thiol or thiolate generate the species [Fe(4)S(4)L(4
      n)(SR*)(n)](2-) (L = SEt, Cl) with n = 1-4. Clusters 1 and 2 were prepared with
      racemic thiols leading to the possible formation of one enantiomeric pair (n = 1)
      and seven diastereomers and their enantiomers (n = 2-4). Reactions were monitored
      by isotropically shifted (1)H NMR spectra in acetonitrile or Me(2)SO. In systems
      affording 1 and 2 as final products, individual mixed-ligand species could not be
      detected. However, crystallization of (Et(4)N)(2)[1] afforded 1-[SS(RS)(RS)] in
      which two sites are disordered because of occupancy of R and S ligands.
      Similarly, (Et(4)N)(2)[2] led to 2-[SSSS], a consequence of spontaneous
      resolution upon crystallization. The clusters 3-[RRRR] and 3-[SSSS] were obtained
      from enantiomerically pure thiols. Successive reactions lead to detection of
      species with n = 1-4 by appearance of four pairs of diastereotopic SCH(2) signals
      in both acetonitrile and Me(2)SO reaction systems. Identical spectra were
      obtained with racemic, R-(-), and S-(+) thiols, indicating that ligand-ligand
      interactions are too weak to allow detection of diastereomers (e.g., [SSSS] vs
      [SSRR]). The stability of 3 in Me(2)SO/H(2)O media is described.

PMID- 21942300
TI  - Effect of acute increases of intraocular pressure on corneal pachymetry in eyes
      treated with travoprost: an animal study.
AB  - PURPOSE: To evaluate "in vivo" the effect of topical travoprost on the central
      corneal thickness (CCT) of rabbit eyes, and the changes in the CCT after acute
      increases of intraocular pressure (IOP) in these eyes. MATERIALS AND METHODS:
      This is an interventional, prospective, case-control, masked study. Topical
      travoprost was applied once daily for one month to the right eye of six New
      Zealand male rabbits, the left eye of each animal served as control. The baseline
      CCT and IOP were measured under general anesthesia. After the IOP was stabilized
      at 15 and 30 mmHg, as registered by direct cannulation of the anterior chamber,
      CCT measurements were measured again at both pressure levels. RESULTS: The
      baseline CCT was thicker in eyes previously treated with travoprost (study group)
      than in control eyes (p < 0.01). The CCT decreased in both groups when IOP was
      raised to 15 and 30 mmHg, and there were no statistically significant difference
      in absolute CCT values between study and control eyes at any of the IOP levels (p
      = 0.5). However, the amount of CCT decrease from baseline values was greater in
      eyes previously treated with travoprost (study group) than in control ones, at
      both 15 and 30 mmHg IOP levels (p = 0.01 and 0.02, respectively). CONCLUSIONS:
      Rabbit corneas treated with topical travoprost show a different strain response
      to acute increases in IOP than control eyes.

PMID- 21942301
TI  - Analysis of the comparative effectiveness of 3 oral bisphosphonates in a large
      managed care organization: adherence, fracture rates, and all-cause cost.
AB  - BACKGROUND: Despite widespread availability and use of oral bisphosphonates,
      fracture rates and associated medical costs are still high. Differences in
      fracture risk among these agents, if any, have not been quantified due to the
      lack of high-quality, head-to-head, randomized, controlled trials assessing this
      outcome. Randomized, placebo-controlled trials have shown that alendronate and
      risedronate reduce rates of both vertebral and nonvertebral fractures, whereas
      only reduction in vertebral fractures has been found for ibandronate. OBJECTIVE:
      To determine if there were any differences among 3 oral bisphosphonates in
      adherence, total cost of care, and effectiveness in reducing fracture rates in a
      large managed care population. METHODS: Administrative, longitudinal pharmacy and
      medical claims data were obtained from 14 geographically diverse health plans in
      the United States covering approximately 14 million members. Sampled members had
      at least 1 pharmacy claim for alendronate, risedronate, or ibandronate during the
      intake period (January 1, 2005, through October 31, 2007). The date of the first
      pharmacy claim for osteoporosis medications within the intake period was the
      index date. Members were followed for either 12, 24, or 36 months, depending on
      length of continuous health plan eligibility. Medication possession ratio (MPR)
      was measured using a total days supply that was calculated by multiplying the
      total quantity dispensed by the suggested days supply per unit of dispensing
      based on manufacturer-recommended dosing. For members who switched bisphosphonate
      strengths or medications, the estimated days supply was summed for all
      osteoporosis medications during the follow-up, including overlapping days supply.
      Outcomes included (a) the first incident fracture and percentages of members with
      at least 1 fracture after 6 months post-index; (b) the number of days from index
      to the first incident fracture, measured as time to event in Cox proportional
      hazards regression analysis; and (c) total all-cause health care costs (health
      plan allowed amount including member cost share). RESULTS: A total of 45,939
      members were included (n = 24,909 alendronate, n = 13,834 risedronate, n = 7,196
      ibandronate). In the 12-month analysis, MPRs were comparable (means = 0.57-0.58)
      for the 3 medications. After 24 months, MPRs had dropped for all medications, but
      those of both alendronate (mean = 0.50, 95% CI = 0.49-0.50) and risedronate (mean
      = 0.50, 95% CI = 0.49-0.51) were slightly higher than that of ibandronate (mean =
      0.47, 95% CI = 0.46-0.48). At 36 months, again the MPRs had dropped for all 3
      medications (means = 0.44-0.47) but were similar. There were no statistically
      significant differences among agents in the percentages of subjects with at least
      1 fracture at 12, 24, or 36 months (36-month rates: alendronate 4.41%,
      risedronate 4.38%, ibandronate 6.28%, P = 0.102). The numbers of subjects with
      fracture(s) per month of follow-up were 0.0020 for alendronate, 0.0021 for
      risedronate, and 0.0022 for ibandronate (P = 0.087 overall). However, after
      adjusting for member characteristics, alendronate users had a 12% lower risk of
      experiencing any incident fracture than ibandronate users (hazard ratio = 0.88,
      95% CI = 0.78-0.99, P = 0.034) within the follow-up period. In the first 12 post
      index months, ibandronate users had higher mean [SD] unadjusted total all-cause
      health care costs ($7,464 [$15,975]) compared with alendronate ($7,233 [$16,671])
      and risedronate ($ 6,983 [$16,870], P less than 0.001 for both comparisons),
      differences of approximately $19 per month and $40 per month, respectively. The
      results of the unadjusted 24-month analysis were similar, but there were no
      significant cost differences at 36 months. Total cost differences for the 3
      medication groups were nonsignificant at 12, 24, and 36 months after adjusting
      for member characteristics. CONCLUSIONS: This retrospective analysis of an
      administrative claims database in a large managed care population showed similar
      rates of adherence and total adjusted all-cause health care costs for
      alendronate, risedronate, and ibandronate. Absolute unadjusted rates of fracture
      were small and did not significantly differ among agents, but after controlling
      for differences in member characteristics, the risk of fracture was 12% lower for
      alendronate users than for ibandronate users.

PMID- 21942302
TI  - Determinants of medicare all-cause costs among elderly patients with renal cell
      carcinoma.
AB  - BACKGROUND: Renal cell carcinoma (RCC) is the third most common genitourinary
      cancer and the most common primary renal neoplasm. Estimates of the economic
      burden of RCC in the United States range from approximately $400 million (in year
      2000 dollars) to $4.4 billion (in year 2005 dollars). Actual costs associated
      with RCC, particularly for elderly Medicare patients who account for 46% of U.S.
      patients hospitalized for RCC, are poorly understood. OBJECTIVE: To estimate all
      cause health care costs associated with RCC using the combined Surveillance
      Epidemiology and End Results (SEER)-Medicare database. METHODS: The sample was
      limited to non-HMO patients aged 65 years or older who were diagnosed with a
      first primary RCC (SEER site recode 59, kidney and renal pelvis) between 1995 and
      2002. Our final sample included 4,938 patients with RCC and 9,876 non-HMO
      noncancer comparison group cases without chronic renal disease drawn from the
      SEER 5% Medicare sample and matched by a propensity score calculated from age,
      gender, race/ethnicity, and comorbidities. Costs were defined as payments made by
      Medicare for all-cause medical treatments including inpatient stays, emergency
      room visits, outpatient procedures, office visits, home health visits, durable
      medical equipment, and hospice care, but excluding out-patient prescription
      drugs. Using the method of Bang and Tsiatis (2000), we estimated cumulative costs
      at 1 and 5 years by estimating average costs for each patient in each month up to
      60 months following diagnosis. Total costs were weighted sums of monthly costs,
      where weights were the inverse probability that the patient was not censored, and
      inverse probabilities were estimated by Kaplan-Meier estimates of time to
      censoring. Using the method of Lin (2000), we performed multivariate analyses of
      costs by fitting each of the 60 monthly costs to linear models that controlled
      for demographic characteristics and comorbidities. Marginal effects of covariates
      on 1- and 5-year costs were obtained by summing the coefficients for months 1
      through 12 and months 1 through 60, respectively. Confidence intervals were
      obtained by bootstrapping. RESULTS: Patients with RCC and matched comparison
      group cases had similar demographic characteristics, comorbidities, and chronic
      conditions. At the start of the fifth year post-diagnosis, there were 1,208
      Medicare RCC cases of the original 4,938 (20.8%). Mean costs per patient per
      month (PPPM) in the first year were $3,673 for patients with RCC and $793 for
      comparison group patients. PPPM costs were higher for RCC patients with more
      advanced stage (i.e., regional or distant) disease. Average cumulative total
      costs for RCC patients were $33,605 per patient in the first year following
      diagnosis and $59,397 per patient in the first 5 years following diagnosis.
      Several patient-specific factors were associated with 1- and 5-year costs in
      multivariate analyses, including age, race/ethnicity, and comorbidities. Among
      RCC patients, treatment with surgery and radiation was associated with higher
      costs per patient than treatment with surgery alone at 1 year ($24,556, 95% CI =
      $16,673-$32,940) and 5 years ($30,540, 95% CI = $17,853-$43,648). RCC patients
      who received chemotherapy as part of their treatment regimen also had
      significantly higher costs per patient than those who received surgery alone at 1
      year ($15,144, 95% CI = $ 9,979-$20,344) and 5 years ($13,440, 95% CI = $1,257
      $27,572). CONCLUSIONS: Newly diagnosed RCC is associated with a significant
      economic burden, which is largely determined by several patient characteristics,
      disease stage, and treatment choice.

PMID- 21942303
TI  - Economic evaluation of denosumab compared with zoledronic acid in hormone
      refractory prostate cancer patients with bone metastases.
AB  - BACKGROUND: Bone metastases are common in patients with hormone-refractory
      prostate cancer. In a study of autopsies of patients with prostate cancer, 65%
      75% had bone metastases. Bone metastases place a substantial economic burden on
      payers with estimated total annual costs of $1.9 billion in the United States.
      Skeletal-related events (SREs), including pathologic fractures, spinal cord
      compression, surgery to bone, and radiation to bone, affect approximately 50% of
      patients with bone metastases. They are associated with a decreased quality of
      life and increased health care costs. Zoledronic acid is an effective treatment
      in preventing SREs in solid tumors and multiple myeloma. Recently, denosumab was
      FDA-approved for prevention of SREs in patients with bone metastases from solid
      tumors. A Phase 3 clinical trial (NCT00321620) demonstrated that denosumab had
      superior efficacy in delaying first and subsequent SREs compared with zoledronic
      acid. However, the economic value of denosumab has not been assessed in patients
      with hormone-refractory prostate cancer. OBJECTIVE: To compare the cost
      effectiveness of denosumab with zoledronic acid in the treatment of bone
      metastases in men with hormone-refractory prostate cancer. METHODS: An Excel
      based Markov model was developed to assess costs and effectiveness associated
      with the 2 treatments over a 1- and 3-year time horizon. Because the evaluation
      was conducted from the perspective of a U.S. third-party payer, only direct costs
      were included. Consistent with the primary outcome in the Phase 3 trial,
      effectiveness was assessed based on the number of SREs. The model consisted of 9
      health states defined by SRE occurrence, SRE history, disease progression, and
      death. A hypothetical cohort of patients with hormone-refractory prostate cancer
      received either denosumab 120 mg or zoledronic acid 4 mg at the model entry and
      transitioned among the 9 health states at the beginning of each 13-week cycle.
      Transition probabilities associated with experiencing the first SRE, subsequent
      SREs, disease progression, and death were primarily derived from the results of
      the Phase 3 clinical trial and were supplemented with published literature. The
      model assumed that a maximum of 1 SRE could occur in each cycle. Drug costs
      included wholesale acquisition cost, health care professional costs associated
      with drug administration, and drug monitoring costs, if applicable. Nondrug costs
      included incremental costs associated with disease progression, costs associated
      with SREs, and terminal care costs, which were derived from the literature.
      Adverse event (AE) costs were estimated based on the incidence rates reported in
      the Phase 3 trial. Resource utilization associated with AEs was estimated based
      on consultation with a senior medical director employed by the study sponsor. All
      costs were presented in 2010 dollars. The base case estimated the incremental
      total cost per SRE avoided over a 1-year time horizon. Results for a 3-year time
      horizon were also estimated. One-way sensitivity analyses and probabilistic
      sensitivity analyses (PSA) were performed to test the robustness of the model.
      RESULTS: In the base case, the total per patient costs incurred over 1 year were
      estimated at $35,341 ($19,230 drug costs and $16,111 nondrug costs) for denosumab
      and $27,528 ($10,960 drug costs and $16,569 nondrug costs) for zoledronic acid,
      with an incremental total direct cost of $7,813 for denosumab. The estimated
      numbers of SREs per patient during the 1-year period were 0.49 for denosumab and
      0.60 for zoledronic acid, resulting in an incremental number of SREs of -0.11 in
      the denosumab arm. The estimated incremental total direct costs per SRE avoided
      with the use of denosumab instead of zoledronic acid were $71,027 for 1 year and
      $51,319 for 3 years. The 1-way sensitivity analysis indicated that the results
      were sensitive to the drug costs, median time to first SRE, and increased risk of
      SRE associated with disease progression. Results of the PSA showed that based on
      willingness-to-pay thresholds of $70,000, $50,000, and $30,000 per SRE avoided,
      respectively, denosumab was cost-effective compared with zoledronic acid in
      49.5%, 17.5%, and 0.3% of the cases at 1 year, respectively, and 79.0%, 49.8%,
      and 4.1% of the cases at 3 years, respectively. CONCLUSIONS: Although denosumab
      has demonstrated benefits over zoledronic acid in preventing or delaying SREs in
      a Phase 3 trial, it may be a costly alternative to zoledronic acid from a U.S.
      payer perspective.

PMID- 21942304
TI  - Transportation cost of anticoagulation clinic visits in an urban setting.
AB  - BACKGROUND: Patients being managed on warfarin make frequent or regular visits to
      anticoagulation monitoring appointments. International studies have evaluated
      transportation cost and associated time related to anticoagulation clinic visits.
      To our knowledge, no studies have evaluated the cost of transportation to such
      clinic visits in the United States. OBJECTIVE: To describe the methods of
      transportation and estimate the average total cost of transportation to and from
      an anticoagulation clinic in an urban setting. METHODS: We prospectively
      conducted a survey of patients treated at the Harper Anticoagulation Clinic
      located in Detroit, Michigan, during November 2010. The survey was given to
      patients while waiting at their regularly scheduled clinic appointments and
      included questions regarding mode of transportation, distance traveled in miles,
      parking payment, and time missed from work for clinic appointments. The mean
      distance traveled was translated into cost assuming 50 cents per mile based on
      2010 estimates by the Internal Revenue Service. RESULTS: Sixty patients responded
      to the 11-item survey; response rates for individual items varied because
      participants were instructed to skip questions that did not pertain to them. Of
      the 47 participants responding to demographic questions, 70.2% were female, and
      46.8% were older than 60 years. Transportation by private vehicle (80.0%), either
      driven by patients (41.7%) or someone else (38.3%), was the most common method
      reported. Use of private automobile translated into a cost of $11.19 per round
      trip. Other means of transportation identified include a ride from a medical
      transportation service (10.0%), bus (5.0%), walking (3.3%), and taxi (1.7%). The
      mean (SD) distance traveled to the clinic for all methods of transportation was
      8.34 (7.7) miles. We estimated the average cost of round-trip transportation to
      be $10.78 weighted for all transportation modes. This is a direct nonmedical cost
      that is paid for by most patients out of pocket. However, 9 of 44 (20.5%)
      responded that their insurance plans provided at least some coverage for their
      rides to the anticoagulation clinic. Most participants stated that they did not
      take any time off work for clinic visits (88%) primarily because a large
      proportion of the study population was unemployed or retired. CONCLUSION: The
      round-trip cost of transportation to an anticoagulation clinic in an urban
      setting in the United States may translate into a substantial expense, ranging
      from weekly appointments ($560 annually) to once monthly appointments ($130
      annually).

PMID- 21942305
TI  - Using AHRQ's evidence-based reports to improve managed care pharmacy practice:
      oral antidiabetic agents.

PMID- 21942306
TI  - Using the community pharmacy to identify patients at risk of poor asthma control
      and factors which contribute to this poor control.
AB  - BACKGROUND: Although asthma can be well controlled by appropriate medication
      delivered in an appropriate way at an appropriate time, there is evidence that
      management is often suboptimal. This results in poor asthma control, poor quality
      of life, and significant morbidity. METHODS: The objective of this study was to
      describe a population recruited in community pharmacy identified by trained
      community pharmacists as being at risk for poor asthma outcomes and to identify
      factors associated with poor asthma control. It used a cross-sectional design in
      96 pharmacies in metropolitan and regional New South Wales, Victoria, Queensland,
      and Australian Capital Territory in Australia. Community pharmacists with
      specialized asthma training enrolled 570 patients aged >=18 years with doctor
      diagnosed asthma who were considered at risk of poor asthma outcomes and then
      conducted a comprehensive asthma assessment. In this assessment, asthma control
      was classified using a symptom and activity tool based on self-reported frequency
      of symptoms during the previous month and categorized as poor, fair, or good.
      Asthma history was discussed, and lung function and inhaler technique were also
      assessed by the pharmacist. Medication use/adherence was recorded from both
      pharmacy records and the Brief Medication Questionnaire (BMQ). RESULTS: The
      symptom and activity tool identified that 437 (77%) recruited patients had poor
      asthma control. Of the 570 patients, 117 (21%) smoked, 108 (19%) had an action
      plan, 372 (69%) used combination of inhaled corticosteroid (ICS)/long-acting
      beta(2)-agonist (LABA) medications, and only 17-28% (depending on device) used
      their inhaler device correctly. In terms of adherence, 90% had their ICS or
      ICS/LABA dispensed <6 times in the previous 6 months, which is inconsistent with
      regular use; this low adherence was confirmed from the BMQ scores. A logistic
      regression model showed that patients who smoked had incorrect inhaler technique
      or low adherence (assessed by either dispensing history or BMQ) and were more
      likely to have poor control. CONCLUSION: Community pharmacists were able to
      identify patients with asthma at risk of suboptimal control, and factors that
      contributed to this were elicited. This poorly controlled group that was
      identified may not be visible or accessible to other health-care professionals.
      There is an opportunity within pharmacies to target poorly controlled asthma and
      provide timely and tailored interventions.

PMID- 21942307
TI  - Friction force spectroscopy as a tool to study the strength and structure of
      salivary films.
AB  - In this work, we employ atomic force microscopy based friction force spectroscopy
      to study the strength and structure of salivary films. Specifically, films formed
      on model hydrophobic (methylated silica) and hydrophilic (clean silica) substrata
      have been studied in water at pHs in the range 3.3-7. Results reveal that films
      formed on both types of substrata can be described in terms of two different
      fractions, with only one of them being able to diffuse along the underlying
      substrata. We also show how the protective function of the films is reduced when
      the pH of the surrounding medium is lowered. Specifically, lowering of pH causes
      desorption of some components of the films formed on hydrophobic methylated
      surfaces, leading to weaker layers. In contrast, at low pHs, saliva no longer
      forms a layer on hydrophilic silica surfaces. Instead, an inhomogeneous
      distribution of amorphous aggregates is observed. Our data also suggest that
      hydrophobic materials in the oral cavity might be more easily cleaned from
      adsorbed salivary films. Finally, reproducible differences are observed in
      results from experiments on films from different individuals, validating the
      technique as a tool for clinical diagnosis of the resistance to erosion of
      salivary films.

PMID- 21942308
TI  - Double-phase hydrogel for buccal delivery of tramadol.
AB  - CONTEXT: Treatment of chronic pain is complicated by the evidence that abuse of
      prescription opioids is rising; therefore, in many cases, chronic pain remains
      undertreated. Tramadol is an atypical central analgesic with a mixed mechanism of
      action offering many advantages over conventional opioids. OBJECTIVE: We
      exploited the nonopioid action of tramadol, by bypassing the first-pass effect,
      as well as multiparticulate drug delivery. Our aim was to identify optimal
      formulation parameters for designing polyvinyl alcohol (PVA), single and mixed
      dual cross-linked tramadol microspheres-loaded hydrogel with adequate bioadhesion
      and providing controlled drug release for buccal delivery. METHODS: Microspheres
      characterization was done by scanning electron microscopy and infrared
      spectroscopy. Other investigations comprised the evaluation of yield, drug
      content, particle size, rheology, swelling, mucoadhesion, release, and permeation
      studies through biological membranes all together with testing the
      antinociceptive activity and its attenuation by the antagonist naloxone HCl.
      RESULTS AND CONCLUSION: PVA-alginate microspheres (F3)-loaded carbopol hydrogel
      attained: the highest mucoadhesion time (1436.67 min +/- 5.77) and mucin
      adsorption capacity, shear thinning thixotropic properties with adequate yield
      value and hysteresis area, best drug release (RE = 84.20 +/- 2.07%) and
      permeation efficiency (PE = 65.30 +/- 7.02%). Dissolution and permeation profiles
      were compared using similarity factor; F3-loaded carbogel had the lowest value.
      During in vivo study, the nonsignificant difference between the AUC of the groups
      receiving F3-loaded carbogel buccally with (group 5) and without (group 4)
      administration of naloxone, and between group 4 and the oral group, showed that
      the buccal route may arguably provide an alternative safer route of tramadol
      administration.

PMID- 21942309
TI  - Acylhomoserine lactone production by bacteria associated with cultivated
      mushrooms.
AB  - The main bacterial pathogens of cultivated mushroom as well as mushroom
      associated bacteria, which were isolated from Agaricus bisporus, Pleurotus
      ostreatus and Pleurotus eryngii mushroom niches, were evaluated for the
      production of N-acyl-L-homoserine lactones (AHLs) by using four bioreporters.
      Furthermore, identification of AHLs by LC-ESI-FTICR MS was performed on culture
      filtrates of selected pathogens and mushroom-associated bacteria strains, which
      resulted in inducing at least one of the four bioreporters. Strains of
      Burkolderia gladioli pv. agariciola, Pseudomonas agarici and Pseudomonas gingeri,
      but not those of Pseudomonas tolaasii and Pseudomonas reactans, produced an array
      of AHLs depending on the strain. This is the first report of AHL production by
      mushroom bacterial pathogens. Forty-four of 236 bacterial isolates obtained from
      different niches of cultivated mushrooms, in part identified by the Biolog
      identification system, were demonstrated to produce AHLs. Among them, seven
      mushroom-associated bacterial species were for the first time demonstrated to
      produce the above signal molecules. In the culture filtrates of a certain number
      of isolates/strains the AHL-hydrolyzed forms were also present. The minimal
      signal inducing concentration (MSIC) of selected pure AHLs was also determined
      for the four bioreporters used in this study.

PMID- 21942310
TI  - Health care research that delivers: introduction to the special issue on
      cognitive factors in health care.
AB  - Research that addresses human factors issues in health care has made good
      progress since the landmark 1999 Institute of Medicine report on medical error
      (Kohn, Corrigan, & Donaldson, 1999), yet patient safety remains a persistent
      challenge for the health care system. While this challenge reflects many factors,
      we focus on the need for research that is sufficiently comprehensive to identify
      threats to patient safety, yet specific enough to explain how provider and
      patient factors interact with task and health context to engender these threats.
      Such research should be theory-based, yet also problem-driven; exert experimental
      control over theoretically relevant variables, yet also involve participants,
      tasks, and contexts that represent the problems of interest. A tension exists
      between theory-based, experimentally controlled research on the one hand, and
      problem-driven research with representative situations on the other. The studies
      in this special issue are both informed by theory and guided by application,
      reflecting what Stokes (1997) referred to as "use-inspired basic research."
      Collectively, these studies represent progress toward improving patient safety
      and the quality of health care. However, important work remains to be done to
      significantly improve health care by more comprehensively managing tensions
      between theory and application and different research methodologies. We discuss
      barriers to accomplishing such research in general (the challenge of testing
      theory in situ in rich environments), and specifically in the health care domain.
      Significant progress will require research programs that thoughtfully manage
      mixed methods across a series of converging studies.

PMID- 21942311
TI  - Teaching posttraining: influencing diagnostic strategy with instructions at test.
AB  - It is believed that medical diagnosis involves two complementary processes,
      analytic and similarity-based. There is considerable debate as to which of these
      processes defines diagnostic expertise and how best to teach clinical diagnosis
      and reduce diagnostic errors. The purpose of these studies is to document the use
      of these strategies in medical students. We shifted the balance in use of these
      processes and improved diagnostic accuracy with instructions given posttraining
      at the moment of diagnosis. Analytic processing reflecting the degree to which
      cases contain the diagnostic rules was indexed by the rate of accuracy on typical
      versus atypical cases (typicality effect). Similarity-based processing reflecting
      the degree to which cases resemble previously encountered cases was indexed by
      the rate of accuracy on similar versus dissimilar cases (similarity effect). Two
      studies are presented illustrating that diagnosis involves the coordination of
      analytic and similarity-based processes and that differential instruction given
      at test shifts the balance in the use of these processes. Study 1 illustrated
      that participants adopting an analytic strategy exhibit a larger effect of
      typicality. Participants adopting a similarity-based strategy exhibit a larger
      effect of similarity. The diagnostic approach of students given no instructions
      was predominantly analytic. Dual instructions in which participants first
      employed similarity-based processing followed by the application of rules
      improved overall accuracy. Study 2 investigated two versions of dual instructions
      and illustrated that assessing a case with the rules of diagnosis first may
      inhibit the subsequent use of similarity-based reasoning. The implications for
      diagnostic expertise and pedagogy are discussed.

PMID- 21942312
TI  - Effects of camera arrangement on perceptual-motor performance in minimally
      invasive surgery.
AB  - Minimally invasive surgery (MIS) is performed for a growing number of treatments.
      Whereas open surgery requires large incisions, MIS relies on small incisions
      through which instruments are inserted and tissues are visualized with a camera.
      MIS results in benefits for patients compared with open surgery, but degrades the
      surgeon's perceptual-motor performance. We used a laparoscopic simulator to
      measure effects of type (top, front, side) and number (1, 3) of camera views on
      manual manipulation and manual aiming tasks. These experimental manipulations had
      implications for perceptual and cognitive processing including frame of
      reference, movement compatibility, compression, task-information specificity,
      information integration, attentional demands, and information extraction. Camera
      views generally degraded performance compared with direct viewing, but learning
      occurred. Generally, a top view resulted in the best performance, followed by
      front and side views. Benefits of multiple views depended on practice and the
      direction of grasper movement. Mappings between movement direction and camera
      view, the consistency of those mappings, and task difficulty affected
      performance. The benefits and costs for perceptual and cognitive processing that
      were introduced by a given camera view were not necessarily weighted equally.
      Costs and benefits must be considered specifically for each task and for each
      combination of camera view and movement direction. Surgeons may consider using a
      top view, using side views only when necessary, and using a consistent view when
      performing repetitive movements.

PMID- 21942313
TI  - Differences in attentional strategies by novice and experienced operating theatre
      scrub nurses.
AB  - This study investigated the effect of nursing experience on attention allocation
      and task performance during surgery. The prevention of cases of retained foreign
      bodies after surgery typically depends on scrub nurses, who are responsible for
      performing multiple tasks that impose heavy demands on the nurses' cognitive
      resources. However, the relationship between the level of experiences and
      attention allocation strategies has not been extensively studied. Eye movement
      data were collected from 10 novice and 10 experienced scrub nurses in the
      operating theater for caesarean section surgeries. Visual scanning data, analyzed
      by dividing the workstation into four main areas and the surgery into four
      stages, were compared to the optimum expected value estimated by SEEV (Salience,
      Effort, Expectancy, and Value) model. Both experienced and novice nurses showed
      significant correlations to the optimal percentage dwell time values, and
      significant differences were found in attention allocation optimality between
      experienced and novice nurses, with experienced nurses adhering significantly
      more to the optimal in the stages of high workload. Experienced nurses spent less
      time on the final count and encountered fewer interruptions during the count than
      novices indicating better performance in task management, whereas novice nurses
      switched attention between areas of interest more than experienced nurses. The
      results provide empirical evidence of a relationship between the application of
      optimal visual attention management strategies and performance, opening up
      possibilities to the development of visual attention and interruption training
      for better performance.

PMID- 21942314
TI  - Nurses' behaviors and visual scanning patterns may reduce patient identification
      errors.
AB  - Patient identification (ID) errors occurring during the medication administration
      process can be fatal. The aim of this study is to determine whether differences
      in nurses' behaviors and visual scanning patterns during the medication
      administration process influence their capacities to identify patient ID errors.
      Nurse participants (n = 20) administered medications to 3 patients in a simulated
      clinical setting, with 1 patient having an embedded ID error. Error-identifying
      nurses tended to complete more process steps in a similar amount of time than non
      error-identifying nurses and tended to scan information across artifacts (e.g.,
      ID band, patient chart, medication label) rather than fixating on several pieces
      of information on a single artifact before fixating on another artifact. Non
      error-indentifying nurses tended to increase their durations of off-topic
      conversations-a type of process interruption-over the course of the trials; the
      difference between groups was significant in the trial with the embedded ID
      error. Error-identifying nurses tended to have their most fixations in a row on
      the patient's chart, whereas non-error-identifying nurses did not tend to have a
      single artifact on which they consistently fixated. Finally, error-identifying
      nurses tended to have predictable eye fixation sequences across artifacts,
      whereas non-error-identifying nurses tended to have seemingly random eye fixation
      sequences. This finding has implications for nurse training and the design of
      tools and technologies that support nurses as they complete the medication
      administration process.

PMID- 21942315
TI  - Interactions of team mental models and monitoring behaviors predict team
      performance in simulated anesthesia inductions.
AB  - In the present study, we investigated how two team mental model properties
      (similarity vs. accuracy) and two forms of monitoring behavior (team vs. systems)
      interacted to predict team performance in anesthesia. In particular, we were
      interested in whether the relationship between monitoring behavior and team
      performance was moderated by team mental model properties. Thirty-one two-person
      teams consisting of anesthesia resident and anesthesia nurse were videotaped
      during a simulated anesthesia induction of general anesthesia. Team mental models
      were assessed with a newly developed measurement tool based on the concept
      mapping technique. Monitoring behavior was coded by two organizational
      psychologists using a structured observation system. Team performance was rated
      by two expert anesthetists using a performance-checklist. Moderated multiple
      regression analysis revealed that team mental model similarity moderated the
      relationship between team monitoring and performance; a higher level of team
      monitoring in the absence of a similar team mental model had a negative effect on
      performance. Furthermore, team mental model similarity and accuracy interacted to
      predict team performance. Our findings provide new insights on factors
      influencing the relationship between team processes and team performance in
      health care. When investigating the effectiveness of a specific team coordination
      behavior, team cognition has to be taken into account. This represents a
      necessary and compelling extension of the popular process-outcome relationship on
      which previous teamwork research in health care has focused. Moreover, the
      current study adds further external validity to the concept of team mental models
      by highlighting its usefulness in health care.

PMID- 21942316
TI  - Effective communication of risks to young adults: using message framing and
      visual aids to increase condom use and STD screening.
AB  - Sexually Transmitted Diseases (STDs)-including HIV/AIDS-are among the most common
      infectious diseases in young adults. How can we effectively promote prevention
      and detection of STDs in this high risk population? In a two-phase longitudinal
      experiment we examined the effects of a brief risk awareness intervention (i.e.,
      a sexual health information brochure) in a large sample of sexually active young
      adults (n = 744). We assessed the influence of gain- and loss-framed messages,
      and visual aids, on affective reactions, risk perceptions, attitudes, behavioral
      intentions, and reported behaviors relating to the prevention and detection of
      STDs. Results indicate that gain-framed messages induced greater adherence for
      prevention behaviors (e.g., condom use), whereas loss-framed messages were more
      effective in promoting illness-detecting behaviors (e.g., making an appointment
      with a doctor to discuss about STD screening). The influence of the framed
      messages on prevention and detection of STDs was mediated by changes in
      participants' attitudes toward the health behaviors along with changes in their
      behavioral intentions. Moreover, when visual aids were added to the health
      information, both the gain- and loss-framed messages became equally and highly
      effective in promoting health behaviors. These results converge with other data
      indicating that well-constructed visual aids are often among the most highly
      effective, transparent, fast, memorable, and ethically desirable means of risk
      communication. Theoretical, economic, and public policy implications of these
      results are discussed.

PMID- 21942317
TI  - Accurate monitoring leads to effective control and greater learning of patient
      education materials.
AB  - Effective management of chronic diseases (e.g., diabetes) can depend on the
      extent to which patients can learn and remember disease-relevant information. In
      two experiments, we explored a technique motivated by theories of self-regulated
      learning for improving people's learning of information relevant to managing a
      chronic disease. Materials were passages from patient education booklets on
      diabetes from NIDDK. Session 1 included an initial study trial, Session 2
      included self-regulated restudy, and Session 3 included a final memory test. The
      key manipulation concerned the kind of support provided for self-regulated
      learning during Session 2. In Experiment 1, participants either were prompted to
      self-test and then evaluate their learning before selecting passages to restudy,
      were shown the prompt questions but did not overtly self-test or evaluate
      learning prior to selecting passages, or were not shown any prompts and were
      simply given the menu for selecting passages to restudy. Participants who self
      tested and evaluated learning during Session 2 had a small but significant
      advantage over the other groups on the final test. Secondary analyses provided
      evidence that the performance advantage may have been modest because of
      inaccurate monitoring. Experiment 2 included a group who also self-tested but who
      evaluated their learning using idea-unit judgments (i.e., by checking their
      responses against a list of key ideas from the correct response). Participants
      who self-tested and made idea-unit judgments exhibited a sizable advantage on
      final test performance. Secondary analyses indicated that the performance
      advantage was attributable in part to more accurate monitoring and more effective
      self-regulated learning. An important practical implication is that learning of
      patient education materials can be enhanced by including appropriate support for
      learners' self-regulatory processes.

PMID- 21942318
TI  - Effects of polycrystalline cu substrate on graphene growth by chemical vapor
      deposition.
AB  - Chemical vapor deposition of graphene on Cu often employs polycrystalline Cu
      substrates with diverse facets, grain boundaries (GBs), annealing twins, and
      rough sites. Using scanning electron microscopy (SEM), electron-backscatter
      diffraction (EBSD), and Raman spectroscopy on graphene and Cu, we find that Cu
      substrate crystallography affects graphene growth more than facet roughness. We
      determine that (111) containing facets produce pristine monolayer graphene with
      higher growth rate than (100) containing facets, especially Cu(100). The number
      of graphene defects and nucleation sites appears Cu facet invariant at growth
      temperatures above 900  degrees C. Engineering Cu to have (111) surfaces will
      cause monolayer, uniform graphene growth.

PMID- 21942319
TI  - Theoretical molecular double-core-hole spectroscopy of nucleobases.
AB  - Double-core-hole (DCH) spectra have been investigated for pyrimidine, purine, the
      RNA/DNA nucleobases, and formamide, using the density functional theory (DFT)
      method. DCH spectra of formamide were also examined by the complete-active-space
      self-consistent-field (CASSCF) method. All possible single- and two-site DCH
      (ssDCH and tsDCH) states of the nucleobases were calculated. The generalized
      relaxation energy and interatomic generalized relaxation energy were evaluated
      from the energy differences between ssDCH and single-core-hole (SCH) states and
      between tsDCH and SCH states, respectively. The generalized relaxation energy is
      correlated to natural bond orbital charge, whereas the interatomic generalized
      relaxation energy is correlated to the interatomic distance between the core
      holes at two sites. The present analysis using DCH spectroscopy demonstrates that
      the method is useful for the chemical analysis of large molecular systems.

PMID- 21942320
TI  - Near-complete suppression of surface recombination in solar photoelectrolysis by
      "Co-Pi" catalyst-modified W:BiVO4.
AB  - The influence of an earth-abundant water oxidation electrocatalyst (Co-Pi) on
      solar water oxidation by W:BiVO(4) has been studied using photoelectrochemical
      (PEC) techniques. Modification of W:BiVO(4) photoanode surfaces with Co-Pi has
      yielded a very large (~440 mV) cathodic shift in the onset potential for
      sustained PEC water oxidation at pH 8. PEC experiments with H(2)O(2) as a
      surrogate substrate have revealed that interfacing Co-Pi with these W:BiVO(4)
      photoanodes almost completely eliminates losses due to surface electron-hole
      recombination. The results obtained for W:BiVO(4) are compared with those
      reported recently for Co-Pi/alpha-Fe(2)O(3) photoanodes. The low absolute onset
      potential of ~310 mV vs RHE achieved with the Co-Pi/W:BiVO(4) combination is
      promising for overall solar water splitting in low-cost tandem PEC cells, and is
      encouraging for application of this surface modification strategy to other
      candidate photoanodes.

PMID- 21942324
TI  - Immediate loading of maxillary and mandibular implant-supported fixed complete
      dentures: a 1- to 10-year retrospective study.
AB  - This study evaluated the success rates of 50 full-arch maxillary and/or
      mandibular implant-supported fixed complete dentures. After a mean follow-up time
      of 42.1 months, 269 implants remained in function, which corresponded to
      cumulative implant success rates of 85.2% and an absolute success rate of 90.6%
      (269/297 implants). This study suggested that higher implant failure rates might
      be associated with a dental history of bruxism (29.3%) vs no history of bruxism
      (4.6%) and surgeons with limited experience (<=5 years; 12.2%) vs surgeons with
      experience (2.4%).

PMID- 21942325
TI  - NMR spectrometers as "magnetic tongues": prediction of sensory descriptors in
      canned tomatoes.
AB  - The perception of odor and flavor of food is a complicated physiological and
      psychological process that cannot be explained by simple models. Quantitative
      descriptive analysis is a technique used to describe sensory features.
      Nevertheless, the availability of a number of instrumental techniques has opened
      up the possibility to calibrate the sensory perception. In this frame, we have
      tested the potentiality of nuclear magnetic resonance spectroscopy as a
      predictive tool to measure sensory descriptors. In particular, we have used an
      NMR metabolomic approach that allowed us to differentiate the analyzed samples
      based on their chemical composition. We were able to correlate the NMR
      metabolomic fingerprints recorded for canned tomato samples to the sensory
      descriptors bitterness, sweetness, sourness, saltiness, tomato and metal taste,
      redness, and density, suggesting that NMR might be a very useful tool for the
      characterization of sensory features of tomatoes.

PMID- 21942326
TI  - Synthesis of 2'-N-methylamino-2'-deoxyguanosine and 2'-N,N-dimethylamino-2'
      deoxyguanosine and their incorporation into RNA by phosphoramidite chemistry.
AB  - The 2'-hydroxyl groups within RNA contribute in essential ways to RNA structure
      and function. Previously, we designed an atomic mutation cycle (AMC) that uses
      ribonucleoside analogues bearing different C-2'-substituents, including -OCH(3), 
      NH(2), -NHMe, and -NMe(2), to identify hydroxyl groups within RNA that donate
      functionally significant hydrogen bonds. To enable AMC analysis of the
      nucleophilic guanosine cofactor in the Tetrahymena ribozyme reaction and at other
      guanosines whose 2'-hydroxyl groups impart critical functional contributions, we
      describe here the syntheses of 2'-methylamino-2'-deoxyguanosine (G(NHMe)) and 2'
      N,N-dimethylamino-2'-deoxyguanosine (G(NMe(2))) and their corresponding
      phosphoramidites. The key step in obtaining the nucleosides involved S(N)2
      displacement of 2'-beta-triflate from an appropriate guanosine derivative by
      methylamine or dimethylamine. We readily obtained the G(NMe(2)) phosphoramidite
      and incorporated it into RNA. However, the G(NHMe) phosphoramidite posed a
      significantly greater challenge due to lack of a suitable -2'-NHMe protecting
      group. After testing several strategies, we established that allyloxycarbonyl
      (Alloc) provided suitable protection for 2'-N-methylamino group during the
      phosphoramidite synthesis and the subsequent RNA synthesis. This work enables AMC
      analysis of guanosine's 2'-hydroxyl group within RNA.

PMID- 21942327
TI  - Is there a role for consolidative radiation therapy for aggressive B-cell
      lymphoma in the rituximab era?

PMID- 21942328
TI  - WT1 overexpression at diagnosis may predict favorable outcome in patients with de
      novo non-M3 acute myeloid leukemia.
AB  - We reviewed the frequency and prognostic significance of FLT3 (fms-like tyrosine
      kinase receptor-3) and NPM (nucleophosmin) gene mutations and WT1 (Wilms' tumor)
      and BAALC (brain and acute leukemia, cytoplasmic) gene expression in 100
      consecutive patients with intermediate and poor cytogenetic risk de novo acute
      myeloid leukemia (AML) receiving conventional anthracycline-AraC based therapy.
      We observed a strict relationship between unfavorable karyotype and BAALC >1000
      (p = 0.0001). Multivariate analysis of 81 patients with intermediate karyotype
      revealed that younger age (p = 0.00009), NPM gene mutation (p = 0.002), and WT1
      >75th percentile (>2365) (p = 0.003) were independent, positive factors for
      complete remission (CR). WT1 expression above 2365 was correlated also to longer
      event-free survival (EFS) and overall survival (OS) in the same subset of
      patients (p = 0.003 and p = 0.02, respectively); the same finding occurred in
      younger patients with AML with intermediate karyotype (p = 0.008 and p = 0.01,
      respectively). In patients with intermediate karyotype, FLT3 internal tandem
      duplication (ITD) negatively affected EFS (EFS at 30 months: 30% vs. 6% in FLT3
      ITD negative and FLT3 positive patients, respectively; p = 0.01) and OS (OS at 30
      months: 38% vs. 20%, p = 0.03). The positive prognostic value of high WT1
      expression does not have a clear explanation; it may be implicated either with
      WT1 anti-oncogenic function, or with the stimulating effect of WT1 oncogene on
      the leukemic cellular cycle, possibly associated with an enhanced response to
      chemotherapy.

PMID- 21942329
TI  - Synergistic enhancement of cellular immune responses by the novel Toll receptor
      7/8 agonist 3M-007 and interferon-gamma: implications for therapy of cutaneous T
      cell lymphoma.
AB  - Cutaneous T-cell lymphoma (CTCL) is responsive at all stages to immunotherapy. We
      determined whether a novel agonist for Toll-like receptor (TLR) 7/8 (3M-007)
      combined with either interferon-gamma (IFN-gamma) or interleukin-15 (IL-15) would
      enhance patients' immune responses in vitro. Our data demonstrate that IFN-gamma
      or IL-15 in combination with 007 significantly increases patients' natural killer
      (NK) cytolytic activity against CTCL tumor cell lines and synergistically induces
      dendritic cell cytokines, compared to 007 alone. Microarray studies of gene
      expression of patients' peripheral blood mononuclear cells (PBMCs) primed with
      IFN-gamma followed by stimulation with 007 identified significant up-regulation
      of the expression of IL-12 p35 (alpha-chain), IL-12 p40 (beta-chain), and nine
      IFN-alpha genes. Importantly, the underlying mechanism of increased levels of IFN
      alpha and IL-12 from combined treatment appears to involve IFN regulatory factor
      8 (IRF-8). These results further support our hypothesis that combinations of
      biological modifiers activating different arms of the immune system may provide
      significant therapeutic benefits for patients with advanced CTCL.

PMID- 21942331
TI  - Modeling thermal decomposition mechanisms in gaseous and crystalline molecular
      materials: application to beta-HMX.
AB  - Exploration of initiation of chemistry in materials is especially challenging
      when several coexisting chemical mechanisms are possible and many reactions'
      products are produced. It is even more difficult for complex materials, such as
      molecular, supramolecular, and hierarchical materials and systems. A strategy to
      draw a complete picture of the earliest stages of rapid decomposition reactions
      in molecular materials is presented in this study. The strategy is based on
      theoretical and computational modeling of chemical decomposition reactions in the
      gaseous and crystalline molecular material that has been performed by means of
      combined density functional theory and transition state theory. This study
      reveals how a crystalline field affects materials chemical degradation. We also
      demonstrate how incomplete results, which are often used due to difficulties in
      obtaining comprehensive data, can lead to erroneous conclusions and predictions.
      We discuss our approach in the context of the obtained reaction energies,
      activation barriers, structures of transition states, and reaction rates with the
      example of a representative molecular material, beta-HMX, which tends to
      decompose violently with large energy release upon an external perturbation. The
      performed analysis helps to provide a consistent interpretation of available
      experimental data. The article illustrates that the complete picture of
      decomposition reactions of complex molecular materials, while theoretically
      challenging and computationally demanding, is possible and even practical at this
      point in time.

PMID- 21942330
TI  - Synaptic mitochondrial pathology in Alzheimer's disease.
AB  - SIGNIFICANCE: Synaptic degeneration, an early pathological feature in Alzheimer's
      disease (AD), is closely correlated to impaired cognitive function and memory
      loss. Recent studies suggest that involvement of amyloid-beta peptide (Abeta) in
      synaptic mitochondrial alteration underlies these synaptic lesions. Thus, to
      understand the Abeta-associated synaptic mitochondrial perturbations would
      fortify our understanding of synaptic stress in the pathogenesis of AD. RECENT
      ADVANCES: Increasing evidence suggests that synaptic mitochondrial dysfunction is
      strongly associated with synaptic failure in many neurodegenerative diseases
      including AD. Based on recent findings in human AD subjects, AD animal models,
      and AD cellular models, synaptic mitochondria undergo multiple malfunctions
      including Abeta accumulation, increased oxidative stress, decreased respiration,
      and compromised calcium handling capacity, all of which occur earlier than
      changes seen in nonsynaptic mitochondria before predominant AD pathology. Of
      note, the impact of Abeta on mitochondrial motility and dynamics exacerbates
      synaptic mitochondrial alterations. CRITICAL ISSUES: Synaptic mitochondria
      demonstrate early deficits in AD; in combination with the role that synaptic
      mitochondria play in sustaining synaptic functions, deficits in synaptic
      mitochondria may be a key factor involved in an early synaptic pathology in AD.
      FUTURE DIRECTIONS: The importance of synaptic mitochondria in supporting synapses
      and the high vulnerability of synaptic mitochondria to Abeta make them a
      promising target of new therapeutic strategy for AD.

PMID- 21942332
TI  - Enhancement of antibiotic susceptibility of  Stenotrophomonas maltophilia  using
      a polyclonal antibody developed against an ABC multidrug efflux pump.
AB  - Stenotrophomonas maltophilia is an emerging nosocomial pathogen capable of
      causing healthcare-associated infections, including pneumonia and bacteremia.
      Intrinsic resistance in S. maltophilia is exhibited towards many broad-spectrum
      antibiotics, and treatment recommendations are controversial. One of the major
      causes of antimicrobial resistance is attributed to a robust array of efflux
      pumps that extrude drug compounds from the cell. Using checkerboard and growth
      kinetic assays, we evaluated the in vitro activity of a polyclonal antibody
      raised against an ATP-binding cassette efflux protein in S. maltophilia. Six
      clinical strains of S. maltophilia and one type strain were challenged with co
      trimoxazole, ticarcillin-clavulanate, and ciprofloxacin, alone and in combination
      with antibody. One clinical strain was tested by growth curve experiments for
      each antibiotic-antibody combination. The use of antibody resulted in
      significantly increased susceptibility in 71.4% (15/21) of treatments tested,
      with 33.3% displaying synergy and 38.1% an additive effect. In growth kinetic
      studies, synergy was obtained for each antibiotic-antibody combination. Thus, the
      use of antibody raised against multidrug efflux pumps for the treatment of
      multidrug-resistant organisms warrants further investigation. Antibody targeting
      substrate recognition sites, or other functionally important epitopes, may lead
      to inhibition of multiple efflux pumps that share the same substrate and is an
      attractive area that should be explored.

PMID- 21942333
TI  - Understanding the molecular mechanism of enzyme dynamics of ribonuclease A
      through protonation/deprotonation of HIS48.
AB  - Molecular dynamics simulation is carried out to investigate the enzyme dynamics
      of RNase A with the HIS48 in three different states (HIP48 (protonated), HID48
      (deprotonated), and H48A mutant). Insights derived from the current theoretical
      study, combined with the available experimental observations, enabled us to
      provide a microscopic picture for the efficient enzyme dynamics. Specifically, in
      the "closed" state or HIP48, the N-terminal hinge loop is intact and the enzyme
      remains in a relatively stable conformation which is preferred for catalytic
      reaction. Deprotonation of HIS48 induces the denaturing of this hinge-loop into a
      3(10)-helix, causing it to break the original interaction network around the loop
      1 and drive the partial unfolding of the N-terminal. The enhanced dynamic motion
      of the N-terminal helix facilitates the release of the catalytic product (the
      rate limiting step) and speeds up the overall catalytic process. The current
      study established that HIS49 acts as a modulator for the transformation of
      conformational states through the perturbing of hydrogen bond networks across
      loop-1, the N-terminal helix, and other residues nearby. Our study suggests that
      HIS48 may also serve to transport loop-1's kinetic energy to the reaction center.

PMID- 21942334
TI  - A quasi-experimental analysis of the influence of neighborhood disadvantage on
      child and adolescent conduct problems.
AB  - A quasi-experimental comparison of cousins differentially exposed to levels of
      neighborhood disadvantage (ND) was used with extensive measured covariates to
      test the hypothesis that neighborhood risk has independent effects on youth
      conduct problems (CPs). Multilevel analyses were based on mother-rated ND and
      both mother-reported CPs across 4-13 years (n = 7,077) and youth-reported CPs
      across 10-13 years (n = 4,524) from the Children of the National Longitudinal
      Survey of Youth. ND was robustly related to CPs reported by both informants when
      controlling for both measured risk factors that are correlated with ND and
      unmeasured confounds. These findings are consistent with the hypothesis that ND
      has influence on conduct problems.

PMID- 21942336
TI  - How are depression and autobiographical memory retrieval related to culture?
AB  - This study investigated how culture influences the association between
      autobiographical memory retrieval and depression. Thirty clinically depressed
      patients and 30 controls, 15 each from Britain and Taiwan, completed the English
      and Chinese versions of the Autobiographical Memory Cueing Task (AMT). Overall,
      the depressed individuals from both cultural groups retrieved significantly fewer
      specific and more categoric autobiographical memories than their matched,
      nondepressed controls. Within the control groups, the British participants
      retrieved significantly more specific autobiographical memories and fewer
      categoric memories than their Taiwanese counterparts. These results suggest that
      difficulty in retrieving specific autobiographical memories typical of depression
      may be a cognitive bias that occurs across cultures.

PMID- 21942335
TI  - Understanding general and specific connections between psychopathology and
      marital distress: a model based approach.
AB  - Marital distress is linked to many types of mental disorders; however, no study
      to date has examined this link in the context of empirically based hierarchical
      models of psychopathology. There may be general associations between low levels
      of marital quality and broad groups of comorbid psychiatric disorders as well as
      links between marital adjustment and specific types of mental disorders. The
      authors examined this issue in a sample (N = 929 couples) of currently married
      couples from the Minnesota Twin Family Study who completed self-report measures
      of relationship adjustment and were also assessed for common mental disorders.
      Structural equation modeling indicated that (a) higher standing on latent factors
      of internalizing (INT) and externalizing (EXT) psychopathology was associated
      with lower standing on latent factors of general marital adjustment for both
      husbands and wives, (b) the magnitude of these effects was similar across
      husbands and wives, and (c) there were no residual associations between any
      specific mental disorder and overall relationship adjustment after controlling
      for the INT and EXT factors. These findings point to the utility of hierarchical
      models in understanding psychopathology and its correlates. Much of the link
      between mental disorder and marital distress operated at the level of broad
      spectrums of psychopathological variation (i.e., higher levels of marital
      distress were associated with disorder comorbidity), suggesting that the
      temperamental core of these spectrums contributes not only to symptoms of mental
      illness but to the behaviors that lead to impaired marital quality in adulthood.

PMID- 21942337
TI  - Electrochemical nanosensor for real-time direct imaging of nitric oxide in living
      brain.
AB  - As gaseous nitric oxide (NO), a critical and multifaceted biomarker, diffuses
      easily once released, identifying the precise sources of NO release is a
      challenge. This study developed a new technique for real-time in vivo direct NO
      imaging by coupling an amperometric NO nanosensor with scanning electrochemical
      microscopy. This technique provides three-dimensional information of the NO
      releasing sites in an intact living mouse brain with high sensitivity and spatial
      resolution. Immunohistochemical analysis was carried out to confirm the
      anatomical reliability of the acquired electrochemical NO image. The real-time NO
      imaging results were well matched with the corresponding immunohistochemical
      analysis of neuronal NO synthase immunoreactive (nNOS-IR) cells, i.e., NO
      releasing sites in a living brain. The imaged NO local concentrations were
      confirmed to be closely related to the location in depth, the size of the nNOS-IR
      cell, and the intensity of nNOS immunoreactivity. This paper demonstrates the
      first direct electrochemical NO imaging of a living brain.

PMID- 21942338
TI  - Textures in polygonal arrangements of square nanoparticles in nematic liquid
      crystal matrices.
AB  - A systematic analysis of defect textures in faceted nanoparticles with polygonal
      configurations embedded in a nematic matrix is performed using the Landau-de
      Gennes model, homeotropic strong anchoring in a square domain with uniform
      alignment in the outer boundaries. Defect and textures are analyzed as functions
      of temperature T, polygon size R, and polygon number N. For nematic
      nanocomposites, the texture satisfies a defect charge balance equation between
      bulk and surface (particle corner) charges. Upon decreasing the temperature, the
      central bulk defects split and together with other -1/2 bulk defects are absorbed
      by the nanoparticle's corners. Increasing the lattice size decreases confinement
      and eliminates bulk defects. Increasing the polygon number increases the central
      defect charge at high temperature and the number of surface defects at lower
      temperatures. The excess energy per particle is lower in even than in odd
      polygons, and it is minimized for a square particle arrangement. These discrete
      modeling results show for first time that, even under strong anchoring, defects
      are attached to particles as corner defects, leaving behind a low energy
      homogeneous orientation field that favors nanoparticle ordering in nematic
      matrices. These new insights are consistent with recent thermodynamic approaches
      to nematic nanocomposites that predict the existence of novel nematic/crystal
      phases and can be used to design nanocomposites with orientational and positional
      order.

PMID- 21942339
TI  - Synthesis of colloidal HgTe quantum dots for narrow mid-IR emission and
      detection.
AB  - HgTe colloidal quantum dots are prepared via a simple two-step injection method.
      Absorption and photodetection with sharp edges, as well as narrow
      photoluminescence, are tunable across the near and mid-IR between 1.3 and 5 MUm.

PMID- 21942342
TI  - Effect of selenium-enriched probiotics on laying performance, egg quality, egg
      selenium content, and egg glutathione peroxidase activity.
AB  - A 35-day experiment was conducted to evaluate the effect of selenium-enriched
      probiotics (SP) on laying performance, egg quality, egg selenium (Se) content,
      and egg glutathione peroxidase (GPX) activity. Five hundred 58-week-old Rohman
      laying hens were randomly allotted to 5 dietary treatments of 100 each. Each
      treatment had 5 replicates, and each replicate had 5 cages with 4 hens per cage.
      The SP was supplemented to a corn-soybean-meal basal diet at 3 different levels
      that supplied total Se at 0.2, 0.5, and 1.0 mg/kg. The basal diet served as a
      blank control, while the basal diet with supplemental probiotics served as a
      probiotics control. The results showed that dietary SP supplementation not only
      increased (p < 0.05) the rate of egg laying, day egg weight, mean egg weight, egg
      Se content, and egg GPX activity but also decreased (p < 0.05) the feed:egg ratio
      and egg cholesterol content. The egg Se content was gradually increased (p <
      0.05) along with the increasing level of dietary Se. The SP supplementation also
      slowed down (p < 0.05) the drop of Haugh units (HU) of eggs stored at room
      temperature. The egg GPX activity had a positive correlation (p < 0.01) with egg
      Se content and a negative correlation (p < 0.01) with egg HU drop. These results
      suggested that Se contents, GPX activity, and HU of eggs were affected by the
      dietary Se level, whereas the egg-laying performance and egg cholesterol content
      were affected by the dietary probiotics. It was concluded that this SP is an
      effective feed additive that combines the organic Se benefit for hen and human
      health with the probiotics benefit for laying hen production performance. It was
      also suggested that the eggs from hens fed this SP can serve as a nutraceutical
      food with high Se and low cholesterol contents for both healthy people and
      patients with hyperlipidemia, fatty liver, or cardiovascular disease.

PMID- 21942343
TI  - MRDCI study of the low-lying electronic states of PbSi.
AB  - Electronic states of the PbSi molecule up to 4 eV have been studied by carrying
      out ab initio based MRDCI calculations which include relativistic effective core
      potentials (RECPs) of both the atoms. The use of semicore RECPs of Pb produces
      better dissociation limits than the full-core one. However, the (3)P(0)-(3)P(1)
      splitting due to Pb is underestimated by about 4000 cm(-1). At least 25 bound
      electronic states of the Lambda-S symmetry are predicted for PbSi. The computed
      zero-field-splitting in the ground state is about 544 cm(-1). A strong spin-orbit
      mixing changes the nature of the potential energy curves of many Omega states.
      The overall splitting among the spin components of A(3)Pi is computed to be 4067
      cm(-1). However, the largest spin-orbit splitting is reported for the (3)Delta
      state. A number of spin-allowed and spin-forbidden transitions are predicted. The
      partial radiative lifetime for the A(3)Pi-X(3)Sigma(-) transition is of the order
      of milliseconds. The computed bond energy in the ground state is 1.68 eV,
      considering the spin-orbit coupling. The vertical ionization energy for the
      ionization to the X(4)Sigma(-) ground state of PbSi(+) is about 6.93 eV computed
      at the same level of calculations.

PMID- 21942344
TI  - Pressure-responsive curvature change of a "rigid" geodesic ligand in a (3,24)
      connected mesoporous metal-organic framework.
AB  - A (3,24)-connected mesoporous metal-organic framework, PCN-69, was synthesized by
      linking a hexatopic ligand btti with dicopper paddlewheel clusters. This material
      has rigid connectivity but a flexible framework, which has been attributed to a
      curvature change of the ligand.

PMID- 21942345
TI  - Moving out: from sterol transport to drug resistance - the ABCG subfamily of
      efflux pumps.
AB  - The ATP binding cassette (ABC) proteins are typically ATP-driven transmembrane
      pumps that have been evolutionarily conserved from bacteria to humans. In humans
      these transporters are subdivided into seven subfamilies, ranging from A to G.
      The ABCG subfamily of transporters is the primary focus of this review. This
      subfamily of proteins has been conserved throughout evolution and plays a central
      role in several cellular processes, such as sterol homeostasis and multidrug
      resistance. Functional polymorphisms/mutations in some of these G-subfamily
      transporters have clinical consequences in humans.

PMID- 21942351
TI  - Separated carbon nanotube macroelectronics for active matrix organic light
      emitting diode displays.
AB  - Active matrix organic light-emitting diode (AMOLED) display holds great potential
      for the next generation visual technologies due to its high light efficiency,
      flexibility, lightweight, and low-temperature processing. However, suitable thin
      film transistors (TFTs) are required to realize the advantages of AMOLED.
      Preseparated, semiconducting enriched carbon nanotubes are excellent candidates
      for this purpose because of their excellent mobility, high percentage of
      semiconducting nanotubes, and room-temperature processing compatibility. Here we
      report, for the first time, the demonstration of AMOLED displays driven by
      separated nanotube thin-film transistors (SN-TFTs) including key technology
      components, such as large-scale high-yield fabrication of devices with superior
      performance, carbon nanotube film density optimization, bilayer gate dielectric
      for improved substrate adhesion to the deposited nanotube film, and the
      demonstration of monolithically integrated AMOLED display elements with 500
      pixels driven by 1000 SN-TFTs. Our approach can serve as the critical foundation
      for future nanotube-based thin-film display electronics.

PMID- 21942352
TI  - Continuous infusions of terbutaline in asthma - a review.
AB  - BACKGROUND: After the safety issues raised by the Salmeterol Multicenter Asthma
      Research Trial, concerns persist about the safety of agents that cause prolonged
      beta-adrenoceptor stimulation in asthmatic patients. We therefore decided to
      revisit and review the use of continuous subcutaneous infusions of terbutaline
      (CSIT)-a treatment often reserved for those with severe and refractory disease.
      RESULTS: Original studies from the 1980s included 26 patients and showed that
      CSIT was well tolerated with predominately cutaneous side effects despite
      maintaining very high serum levels of terbutaline. CSIT led to improved outcomes
      in approximately 75% of patients which included rises in lowest daily peak
      expiratory flow rate (PEFR), diminution in diurnal variation, reduction in other
      medication requirements, and subjective opinion of symptoms. Almost all patients
      demonstrating an improvement had a wide variation in their pretreatment PEFRs.
      However, in a retrospective follow-up of 42 patients, the only outcome to be
      significantly improved by CSIT was that of mean hospital admissions (p = .031).
      CSIT is theorized to stimulate a discrete set of beta-receptors not accessible by
      the inhaled route as further increases in Forced expiratory volume in one second
      (FEV(1)) occur with concurrent nebulized therapy. CONCLUSION: Although some
      findings are encouraging, they are drawn from small observational studies done at
      a time when the standard management of asthma was quite different from today. No
      randomized controlled trials exist for the use of CSIT, which remains off-license
      for the treatment of asthma in the United Kingdom. Clearly, prospective well
      powered studies are required to fully ascertain its potential benefits and safety
      profile-something that is unlikely to occur given that the use of CSIT remains
      low and appears to be declining.

PMID- 21942353
TI  - Relationship of adipokines with immune response and lung function in obese
      asthmatic and non-asthmatic women.
AB  - BACKGROUND: Obesity is a risk factor for asthma. Studies in mice suggest that the
      adipokines leptin and adiponectin affect asthmatic responses. The purpose of this
      study was to determine if adipokines associated with obesity are (1) altered in
      obese women with asthma compared to controls and (2) associated with increased
      cytokines and chemokines involved in allergic inflammation. METHODS: We performed
      a cross-sectional study of asthmatic and non-asthmatic obese premenopausal women.
      Participants answered questionnaires and performed lung function tests. Serum and
      peripheral blood mononuclear cells (PBMCs) were collected for analysis of
      cytokines and adipokines. RESULTS: A total of 22 asthmatic (mean body mass index
      40.0 +/- 5.1 kg/m(2)) and 20 non-asthmatic women (mean body mass index 41.3 +/-
      5.6 kg/m(2)) participated. We found no difference in serum adipokine
      concentrations between asthmatics and non-asthmatics. Serum adiponectin
      correlated positively with PBMC eotaxin (r(s) = 0.55, p = .0003) and RANTES
      (regulated upon activation, normal T-cell expressed, and secreted) (r(s) = 0.36,
      p = .03), whereas serum leptin correlated negatively with PBMC eotaxin (r(s) = 
      0.34, p = .04). There was a negative correlation between serum adiponectin and
      PBMC interferon-gamma (r(s) = -0.41, p = .01). CONCLUSIONS: Perturbations of
      adipokines that occur in obesity were correlated with decreased cytokine
      production typically associated with allergic responses in PBMC of obese
      premenopausal women. This study suggests that although obese asthmatics may have
      elements of Th2-mediated inflammation, adipokine derangements in obesity are
      associated with Th1 rather than Th2 bias. Obesity has complex effects on allergic
      inflammation and is likely to be important modifier of the pathogenesis of airway
      disease in asthma.

PMID- 21942354
TI  - A comparison of budesonide/formoterol maintenance and reliever therapy versus
      conventional best practice in asthma management in Spain.
AB  - OBJECTIVE: To study the effectiveness and safety in a real-life setting of
      budesonide/formoterol (Symbicort) Maintenance And Reliever Therapy(r) (Symbicort
      SMART(r)), a simplified management approach with one inhaler, compared with
      conventional best practice (CBP) with multiple inhalers in patients with
      persistent asthma. DESIGN: Open-label randomized controlled parallel-group trial,
      6-month treatment. PARTICIPANTS: A total of 654 adult patients, with persistent
      asthma receiving treatment with inhaled corticosteroids (ICS), either alone or in
      conjunction with long-acting beta(2)-agonist. MAIN OUTCOME MEASURES: Time to
      first severe asthma exacerbation and number of severe asthma exacerbations.
      RESULTS: No difference between groups was seen in time to first severe
      exacerbation (p = .2974). Exacerbation rates were low in both groups. A total of
      22 patients in the Symbicort SMART group experienced a total of 24 severe asthma
      exacerbations, and 31 patients in the CBP group experienced a total of 34 severe
      asthma exacerbations (annual rate 0.16 vs. 0.22, p = .2869). The mean daily dose
      of ICS expressed in beclomethasone dipropionate equivalent was significantly
      lower in the Symbicort SMART group (including as-needed use) versus the CBP group
      (799 MUg vs.1184 MUg; p < .001). Mean scores in Asthma Control Questionnaire,
      five-question version, improved significantly in the SMART group compared with
      the CBP group (p = .0292). Symbicort SMART and CBP were equally well tolerated.
      The mean drug cost per patient per 6 months was lower for the patients in the
      SMART group compared with patients receiving CBP (?295.32 vs. ?387.98, p <
      .0001). CONCLUSIONS: A simplified regimen using budesonide/formoterol maintenance
      and reliever therapy (Symbicort SMART) was at least as effective at improving
      clinical control compared with CBP with a significantly lower ICS dose and lower
      drug costs.

PMID- 21942355
TI  - (3 + 3)-Cyclodimerization of donor-acceptor cyclopropanes. Three routes to six
      membered rings.
AB  - The ability of donor-acceptor cyclopropanes to (3 + 3)-cyclodimerize is
      disclosed. It has been found that Lewis acid-induced transformations of 2
      (hetero)arylcyclopropane-1,1-dicarboxylates containing electron-abundant aromatic
      substituents led to the construction of six-membered cyclic systems. Depending on
      the substrate properties and the Lewis acid applied, three types of products can
      be obtained: (1) 1,4-diarylcyclohexanes, (2) 1-aryl-1,2,3,4
      tetrahydronaphthalenes, and (3) 9,10-dihydroanthracenes.

PMID- 21942356
TI  - Eelgrass slabs, a soilless culture substrate that inhibits adhesion of fungi and
      oomycetes and enhances antioxidant activity in tomato.
AB  - Composed of a marine plant,  Zostera  sp., eelgrass slabs are a novel organic
      substrate for soilless cultures used in tomato production. The benefit of using
      eelgrass slabs for growing tomatoes was assessed by comparing it with coconut
      fiber slabs in regard to contamination by  Pythium  spp. and to the antioxidant
      properties of tomato fruits. First, tomato root contamination by Pythium spp. was
      studied by direct plate counting, and a molecular comparison of fungal and
      oomycete communities was conducted using PCR-DHPLC. Second, the antioxidant
      properties of tomato fruits were analyzed by measuring total phenol and
      carotenoid contents and by evaluating radical scavenging activity. Compared to
      plants grown on coconut fiber slabs, those on eelgrass slabs presented a lower
      rate of Pythium spp. root contamination. Moreover, culture on eelgrass slabs
      produced fruits with better radical scavenging activity and higher total phenol
      content compared to controls. Carotenoid content was not affected by the type of
      substrate. This study highlights the value of detrital leaves of Zostera sp. as a
      substrate for soilless culture that reduces root contamination and also promotes
      the production of tomato fruits with better nutritional value.

PMID- 21942358
TI  - Thermal aging of interfacial polymer chains in ethylene-propylene-diene
      terpolymer/aluminum hydroxide composites: solid-state NMR study.
AB  - The possible influence of micrometric-size filler particles on the thermo
      oxidative degradation behavior of the polymer chains at polymer/filler interfaces
      is still an open question. In this study, a cross-linked ethylene-propylene-diene
      (EPDM) terpolymer filled by aluminum trihydrate (ATH) particles is investigated
      using (1)H solid-state NMR. The time evolution of the EPDM network microstructure
      under thermal aging at 80  degrees C is monitored as a function of the exposure
      time and compared to that of an unfilled EPDM network displaying a similar
      initial structure. While nearly no variations of the topology are observed on the
      neat EPDM network over 5 days at 80  degrees C, a significant amount of chain
      scission phenomena are evidenced in EPDM/ATH. A specific surface effect induced
      by ATH on the thermodegradative properties of the polymer chains located in their
      vicinity is thus pointed out. Close to the filler particles, a higher amount of
      chain scissions are detected, and the characteristic length scale related to
      these interfacial regions displaying a significant thermo-oxidation process is
      determined as a function of the aging time.

PMID- 21942357
TI  - Molecular epidemiology and clinical characterization of group A rotavirus
      infections in Tunisian children with acute gastroenteritis.
AB  - Rotaviruses are the most common cause of severe viral gastroenteritis in early
      childhood worldwide. Thus, the objectives of our study were to determine the
      molecular epidemiology and the clinical features of rotavirus gastroenteritis in
      Tunisia. Between January 2003 and April 2007, a prospective study was conducted
      on 788 stool samples collected from children under 12 years of age who were
      suffering from acute gastroenteritis. Rotavirus was detected by multiplex RT-PCR
      in 27% (n = 213) of samples, among them 79.3% (n = 169) cases were
      monoinfections. The frequency of rotavirus infections was significantly higher
      among inpatients (29%) than among outpatients (13%) (P < 0.001). The seasonal
      distribution of rotavirus diarrhea showed a winter peak, with an unusual peak
      from June to September. The mean duration of hospitalization was 6.5 +/- 8.1 days
      and the mean age was 15.8 +/- 22.8 months for rotavirus monoinfections. Fever,
      vomiting, abdominal pain, and dehydration were observed in 88, 98, 13, and 80
      cases, respectively, in children with rotavirus monoinfections. G3P[8] (45.6%)
      and G1P[8] (23.9%) were the most common genotypes found in our study. The
      determination of rotavirus infection prevalence and the characterization of the
      rotavirus strains circulating will help us to better understand the molecular
      biology and epidemiology of the disease in our country.

PMID- 21942359
TI  - Initial success with gubernacular-sparing laparoscopic-assisted Fowler-Stephens
      orchidopexy for intra-abdominal testes.
AB  - A single surgeon's 5-year experience of preserving the gubernaculum in
      laparoscopic-assisted Fowler-Stephens orchidopexy is reported. Thirty-six cases
      of impalpable testes are considered. Sixteen patients were confirmed as having
      intra-abdominal testes, with 20 testes considered to be absent/vanished. At
      follow-up, all testes had a similar volume to the contralateral testis except for
      one that had been considered hypoplastic at the initial operation. Mean follow-up
      was 612 days. The method and potential importance of gubernacular preservation in
      this situation are discussed.

PMID- 21942360
TI  - Laparoscopic infrared imaging--the future vascular map.
AB  - OBJECTIVE: One of the most significant limitations of laparoscopic surgery is the
      inability to achieve tactile assessment of structures during surgical dissection.
      Because blood vessels are naturally warmer than their surroundings, infrared (IR)
      detection can be highly effective in identifying and mapping out their course. In
      recent years, IR detection has been used successfully for this purpose in open
      surgery. Nevertheless, this technology has to be yet employed in laparoscopic
      surgery, where its contribution would be greatest. METHODS: We performed a
      feasibility study using this technology on live porcine models. After insertion
      of IR detectors into the insufflated abdomen, we performed a series of
      laparoscopic procedures. During these operations we evaluated the ability of the
      IR detector to identify blood vessels as well as the effects of local and
      systemic changes in temperature. RESULTS: The IR detector successfully identified
      concealed blood vessels as well as acute bleeding. Cool lavage and insufflation
      with room-temperature CO(2) accentuated IR detection of blood vessels, whereas
      warm CO(2) and systemic temperature changes did not affect detection.
      Additionally, localized heating of tissue on the operative field using
      electrocautery did not interfere with IR sensitivity. CONCLUSION: Laparoscopic IR
      imaging is a feasible method of blood vessel detection in laparoscopic
      procedures. Use of IR blood vessel detection in laparoscopy has a potential to
      enable safer surgery and reduce operative time. Fusion of IR imaging with the
      standard laparoscopic view is currently being developed to allow real-time vessel
      mapping during laparoscopic procedures.

PMID- 21942361
TI  - Systematic review of day-case laparoscopic fundoplication.
AB  - BACKGROUND: The aim of the current study is to review published literature on day
      case laparoscopic fundoplication in adults. DATA SOURCES: Medline, Embase, and
      Cochrane library was searched by using the medical subjects headings "ambulatory
      surgical procedures" and "fundoplication" with further free text search and cross
      references. All articles on planned day-case laparoscopic fundoplication that
      described patient selection criteria, same-day discharge, complications, and
      readmissions were reviewed. CONCLUSIONS: Thirteen cohort studies were included in
      this review. Ten were on planned same-day discharge with a 93% (739 out of 792)
      success, 4% (34) complication, and 5% (39) readmission rate. Three studies were
      on planned 23 hour discharge with a 98% (571 out of 583) success, 4% (25)
      complications, and 1% (5) re-admission rate. Nausea, pain, fatigue, and
      pneumothorax were the commonest causes for overnight admission. Dysphagia and
      pain were the main reasons for readmission. Most patients were satisfied with day
      case laparoscopic fundoplication.

PMID- 21942363
TI  - Effect of a multiporous beta-tricalicum phosphate on bone density around dental
      implants inserted into fresh extraction sockets.
AB  - The aim of this study was to assess, via multi-slice helical computerized
      tomography (CT), the influence of the pure-phase multiporous beta-tricalcium
      phosphate (beta-TCP) on bone density around dental implants inserted into fresh
      extraction sockets. Twenty-eight patients (18 women and 10 men), indicated for
      extraction of their lower premolars and insertion of immediate dental implants,
      were included in this study. They were randomly divided into two equal groups (14
      patients each). Group A received immediate dental implants without any filling
      material around the implants, while in group B, a pure-phase multiporous beta-TCP
      was gently packed into the bone gaps around the implants. Three and 6 months
      after loading the implants, a CT, sagittal and coronal, was made to measure the
      bone density around the implants. The results of the current study have shown
      that the mean values of the bone density measurements around the implants in
      group A were 1150 +/- 205 (range, 645-1460) at 3 months and 1245 +/- 165 (range,
      884-1650) at 6 months after loading the implants. In group B, the mean values of
      the bone density measurements around the implants were 1280 +/- 320 (range, 876
      1790) and 1490 +/- 358 (range, 1061-1965) at 3 and 6 months after loading the
      implants, respectively. The statistical analysis of the collected data showed a
      significant increase in the bone density measurements from 3 to 6 months only in
      group B (P < .05). Also, the difference between group A and B in the bone density
      measurements around the implants was statistically significant (P < .05) at only
      6 months after loading. On the basis of the results presented in this study, it
      may be possible to mention that the pure-phase multiporous beta-TCP may enhance
      the bone density when inserted into the bone gaps around immediate dental
      implants. 

PMID- 21942364
TI  - Aging and mental health in the decade ahead: what psychologists need to know.
AB  - Until relatively recently, most psychologists have had limited professional
      involvement with older adults. With the baby boomers starting to turn 65 years
      old in 2011, sheer numbers of older adults will continue to increase. About 1 in
      5 older adults has a mental disorder, such as dementia. Their needs for mental
      and behavioral health services are not now adequately met, and the decade ahead
      will require an approximate doubling of the current level of psychologists' time
      with older adults. Public policy in the coming decade will face tensions between
      cost containment and facilitation of integrated models of care. Most older adults
      who access mental health services do so in primary care settings, where
      interdisciplinary, collaborative models of care have been found to be quite
      effective. To meet the needs of the aging population, psychologists need to
      increase awareness of competencies for geropsychology practice and knowledge
      regarding dementia diagnosis, screening, and services. Opportunities for
      psychological practice are anticipated to grow in primary care, dementia and
      family caregiving services, decision-making-capacity evaluation, and end-of-life
      care. Aging is an aspect of diversity that can be integrated into psychology
      education across levels of training. Policy advocacy for geropsychology clinical
      services, education, and research remains critical. Psychologists have much to
      offer an aging society.

PMID- 21942365
TI  - Genomic analysis at the single-cell level.
AB  - Studying complex biological systems such as a developing embryo, a tumor, or a
      microbial ecosystem often involves understanding the behavior and heterogeneity
      of the individual cells that constitute the system and their interactions. In
      this review, we discuss a variety of approaches to single-cell genomic analysis.

PMID- 21942367
TI  - Maternal and zygotic control of zebrafish dorsoventral axial patterning.
AB  - Vertebrate development begins with precise molecular, cellular, and morphogenetic
      controls to establish the basic body plan of the embryo. In zebrafish, these
      tightly regulated processes begin during oogenesis and proceed through
      gastrulation to establish and pattern the axes of the embryo. During oogenesis a
      maternal factor is localized to the vegetal pole of the oocyte that is a
      determinant of dorsal tissues. Following fertilization this vegetally localized
      dorsal determinant is asymmetrically translocated in the egg and initiates
      formation of the dorsoventral axis. Dorsoventral axis formation and patterning is
      then mediated by maternal and zygotic factors acting through Wnt, BMP (bone
      morphogenetic protein), Nodal, and FGF (fibroblast growth factor) signaling
      pathways, each of which is required to establish and/or pattern the dorsoventral
      axis. This review addresses recent advances in our understanding of the molecular
      factors and mechanisms that establish and pattern the dorsoventral axis of the
      zebrafish embryo, including establishment of the animal-vegetal axis as it
      relates to formation of the dorsoventral axis.

PMID- 21942366
TI  - Uniting germline and stem cells: the function of Piwi proteins and the piRNA
      pathway in diverse organisms.
AB  - The topipotency of the germline is the full manifestation of the pluri- and
      multipotency of embryonic and adult stem cells, thus the germline and stem cells
      must share common mechanisms that guarantee their multipotentials in development.
      One of the few such known shared mechanisms is represented by Piwi proteins,
      which constitute one of the two subfamilies of the Argonaute protein family. Piwi
      proteins bind to Piwi-interacting RNAs (piRNAs) that are generally 26 to 31
      nucleotides in length. Both Piwi proteins and piRNAs are most abundantly
      expressed in the germline. Moreover, Piwi proteins are expressed broadly in
      certain types of somatic stem/progenitor cells and other somatic cells across
      animal phylogeny. Recent studies indicate that the Piwi-piRNA pathway mediates
      epigenetic programming and posttranscriptional regulation, which may be
      responsible for its function in germline specification, gametogenesis, stem cell
      maintenance, transposon silencing, and genome integrity in diverse organisms.

PMID- 21942369
TI  - Genomic imprinting: a mammalian epigenetic discovery model.
AB  - Genomic imprinting is an epigenetic process leading to parental-specific
      expression of one to two percent of mammalian genes that offers one of the best
      model systems for a molecular analysis of epigenetic regulation in development
      and disease. In the twenty years since the first imprinted gene was identified,
      this model has had a significant impact on decoding epigenetic information in
      mammals. So far it has led to the discovery of long-range cis-acting control
      elements whose epigenetic state regulates small clusters of genes and of unusual
      macro noncoding RNAs (ncRNAs) that directly repress genes in cis, and critically,
      it has demonstrated that one biological role of DNA methylation is to allow
      expression of genes normally repressed by default. This review describes the
      progress in understanding how imprinted protein-coding genes are silenced; in
      particular, it focuses on the role of macro ncRNAs that have broad relevance as a
      potential new layer of regulatory information in the mammalian genome.

PMID- 21942370
TI  - Oxidative atom-transfer to a trimanganese complex to form Mn6(MU6-E) (E = O, N)
      clusters featuring interstitial oxide and nitride functionalities.
AB  - Utilizing a hexadentate ligand platform, a trinuclear manganese complex of the
      type ((H)L)Mn(3)(thf)(3) was synthesized and characterized ([(H)L](6-) =
      [MeC(CH(2)N(C(6)H(4)-o-NH))(3)](6-)). The pale-orange, formally divalent
      trimanganese complex rapidly reacts with O-atom transfer reagents to afford the
      MU(6)-oxo complex ((H)L)(2)Mn(6)(MU(6)-O)(NCMe)(4), where two trinuclear subunits
      bind the central O-atom and the ((H)L) ligands cooperatively bind both trinuclear
      subunits. The trimanganese complex ((H)L)Mn(3)(thf)(3) rapidly consumes inorganic
      azide ([N(3)]NBu(4)) to afford a dianionic hexanuclear nitride complex
      [((H)L)(2)Mn(6)(MU(6)-N)](NBu(4))(2), which subsequently can be oxidized with
      elemental iodine to ((H)L)(2)Mn(6)(MU(6)-N)(NCMe)(4). EPR and alkylation of the
      interstitial light atom substituent were used to distinguish the nitride from the
      oxo complex. The oxo and oxidized nitride complexes give rise to well-defined
      Mn(II) and Mn(III) sites, determined by bond valence summation, while the
      dianionic nitride shows a more symmetric complex, giving rise to
      indistinguishable ion oxidation states based on crystal structure bond metrics.

PMID- 21942368
TI  - Sex in fungi.
AB  - Sexual reproduction enables genetic exchange in eukaryotic organisms as diverse
      as fungi, animals, plants, and ciliates. Given its ubiquity, sex is thought to
      have evolved once, possibly concomitant with or shortly after the origin of
      eukaryotic organisms themselves. The basic principles of sex are conserved,
      including ploidy changes, the formation of gametes via meiosis, mate recognition,
      and cell-cell fusion leading to the production of a zygote. Although the basic
      tenants are shared, sex determination and sexual reproduction occur in myriad
      forms throughout nature, including outbreeding systems with more than two mating
      types or sexes, unisexual selfing, and even examples in which organisms switch
      mating type. As robust and diverse genetic models, fungi provide insights into
      the molecular nature of sex, sexual specification, and evolution to advance our
      understanding of sexual reproduction and its impact throughout the eukaryotic
      tree of life.

PMID- 21942372
TI  - Quantitative detection of hazelnut (Corylus avellana) in cookies: ELISA versus
      real-time PCR.
AB  - Hazelnuts (Corylus avellana) are used widely in the food industry, especially in
      confectionery, where they are used raw, roasted, or in a processed formulation
      (e.g., praline paste and hazelnut oil). Hazelnuts contain multiple allergenic
      proteins, which can induce an allergic reaction associated with symptoms ranging
      from mild irritation to life-threatening anaphylactic shock. To date,
      immunochemical (e.g., ELISA or dipstick) and PCR-based analyses are the only
      methods available that can be applied as routine tests. The aim of this study is
      to make a comparative evaluation of the effectiveness of ELISA and real-time PCR
      in detecting and correctly quantifying hazelnut in food model systems. To this
      end, the performances of two commercial ELISAs were compared to those of two
      commercial and one in-house-developed real-time PCR assays. The results showed
      that although ELISA seemed to be more sensitive compared to real-time PCR, both
      detection techniques suffered from matrix effects and lacked robustness with
      regard to food processing. As these impacts were highly variable among the
      different evaluated assays (both ELISA and real-time PCR), no firm conclusion can
      be made as to which technique is suited best to detect hazelnut in (processed)
      food products. In this regard, the current lack of appropriate DNA calibrators to
      quantify an allergenic ingredient by means of real-time PCR is highlighted.

PMID- 21942371
TI  - Influence of viral vector-mediated delivery of superoxide dismutase and catalase
      to the hippocampus on spatial learning and memory during aging.
AB  - AIMS: Studies employing transgenic mice indicate that overexpression of
      superoxide dismutase 1 (SOD1) improves memory during aging. It is unclear whether
      the improvement is due to a lifetime of overexpression, decreasing the
      accumulation of oxidized molecules, or if increasing antioxidant enzymes in older
      animals could reduce oxidative damage and improve cognitive function. We used
      adeno-associated virus to deliver antioxidant enzymes (SOD1, SOD2, catalase
      [CAT], and SOD1+CAT) to the hippocampus of young (4 months) and aged (19 months)
      F344/BN F1 male rats and examined memory-related behavioral performance 1 month
      and 4 months postinjection. RESULTS: Overexpression of antioxidant enzymes
      reduced oxidative damage; however, memory function was not related to the level
      of oxidative damage. Increased expression of SOD1, initiated in advanced age,
      impaired learning. Increased expression of SOD1+CAT provided protection from
      impairments associated with overexpression of SOD1 alone and appears to guard
      against cognitive impairments in advanced age. INNOVATION: Viral vector gene
      delivery provides a novel approach to test the hypothesis that increased
      expression of antioxidant enzymes, specifically in hippocampal neurons, will
      provide protection from age-related cognitive decline. Further, expression of
      multiple vectors permits more detailed investigation of mechanistic pathways.
      CONCLUSION: Oxidative stress is a likely component of aging; however, it is
      unclear whether increased production of reactive oxygen species or the
      accumulation of oxidative damage is the primary cause of functional decline. The
      results provide support for the idea that altered redox-sensitive signaling
      rather than the accumulation of damage may be of greater significance in the
      emergence of age-related learning and memory deficits.

PMID- 21942373
TI  - Possibilities to increase the effectiveness of doxorubicin in cancer cells
      killing.
AB  - Anthracycline antibiotic doxorubicin (DOX) belongs among the most important
      antineoplastics used in cancer therapy. Unfortunately, its cytostatic effect in
      therapeutic doses is frequently insufficient; but the use of higher DOX doses is
      limited by the development of systemic toxicity, especially cardiotoxicity.
      Therefore, a searching for some possibilities of how to increase DOX efficacy in
      cancer cells, and minimizing associated toxicities to noncancerous tissues, is in
      the forefront of scientific research. Many approaches are based on altered DOX
      metabolism. The classical strategies include an enhancing of DOX uptake by cancer
      cells and/or an activation of DOX prodrug within cancer cells via liposomal
      encapsulation or conjugation with antibodies, peptides, or synthetic polymers.
      The diminishing of DOX deactivation, restriction of DOX efflux from cancer cells,
      decreased antioxidant defense of cancer cells, changes in cell cycle, or
      modulation of signaling pathways represent newer approaches in increasing DOX
      toxicity in tumors. Each way has certain advantages and limitations. The aim of
      this review was not to collect all reported results, but to bring an overview of
      various approaches and a summary of their principles. Possible advantages,
      disadvantages, and further perspectives are discussed and evaluated.

PMID- 21942374
TI  - Mapping of the primary mannose binding site of pradimicin A.
AB  - Pradimicin A (PRM-A) is an actinomycete-derived antibiotic with the lectin-like
      property of being able to recognize D-mannopyranoside (Man) in the presence of
      Ca(2+) ion. PRM-A and its derivatives have been attracting a great deal of
      attention as the only family of natural carbohydrate receptors with nonpeptidic
      skeleton and, more recently, as conceptually novel drug candidates for human
      immunodeficiency virus (HIV). Despite its scientific interest and potential
      therapeutic importance, understanding how PRM-A recognizes Man has been severely
      limited. Conventional interaction analysis of PRM-A with Man in solution has been
      frustrated by aggregation of PRM-A and the three-component equilibrium consisting
      of the [PRM-A(2)/Ca(2+)], [PRM-A(2)/Ca(2+)/Man(2)], [PRM-A(2)/Ca(2+)/Man(4)]
      complexes, and their mixed oligomers. In this Article, we demonstrate the
      interaction analysis of PRM-A with methyl alpha-D-mannopyranoside (Man-OMe) in
      the solid state, which benefits from aggregate-forming propensity of PRM-A and
      eliminates the problem associated with the complicated equilibrium in solution.
      Isothermal titration calorimetry (ITC) analysis and coprecipitation experiments
      revealed that the primary Man binding of PRM-A is markedly tighter than the
      secondary one, leading to preparation of the solid aggregate solely composed of
      the [PRM-A(2)/Ca(2+)/Man-OMe(2)] complex. The simple 1:1 complexes of
      biosynthetically (13)C-enriched PRM-As and [(13)C(6)]Man-OMe facilitated the
      analysis of the primary Man binding of PRM-A by two-dimensional dipolar-assisted
      rotational resonance (2D-DARR), which clearly identified that the cavity
      consisted of D-alanine moiety and ABC rings of PRM-A is the Man binding site.
      Interestingly, the proposed Man binding site of PRM-A seems to resemble the
      typical architecture of artificial carbohydrate receptors.

PMID- 21942375
TI  - Using stop-flow lithography to produce opaque microparticles: synthesis and
      modeling.
AB  - We report on modeling and experimental studies of the synthesis of opaque
      microparticles made via stop-flow lithography. Opaque magnetic beads and UV
      absorbing dyes incorporated into hydrogel microparticles during synthesis changed
      the height and the degree of cross-linking of the polymer matrices formed. The
      effect of the concentration of these opaque materials on the particle height was
      determined experimentally and agreed well with model predictions based on the
      photopolymerization process over a wide range of UV absorbance. We also created
      particles with two independent anisotropies, magnetic and geometric, by applying
      magnetic fields during particle synthesis. Our work provides a platform for
      rational design of lithographic patterned opaque particles and also a new class
      of structured magnetic microparticles.

PMID- 21942376
TI  - Hybrid quantum mechanical/molecular mechanics study of the S(N)2 reaction of
      CH3Cl+OH- in water.
AB  - The S(N)2 mechanism for the reaction of CH(3)Cl + OH(-) in aqueous solution was
      investigated using combined quantum mechanical and molecular mechanics
      methodology. We analyzed structures of reactant, transition, and product states
      along the reaction pathway. The free energy profile was calculated using the
      multilayered representation with the DFT and CCSD(T) level of theory for the
      quantum-mechanical description of the reactive region. Our results show that the
      aqueous environment has a significant impact on the reaction process. We find
      that solvation energy contribution raises the reaction barrier by ~18.9 kcal/mol
      and the reaction free energy by ~24.5 kcal/mol. The presence of the solvent also
      induces perturbations in the electronic structure of the solute leading to an
      increase of 3.5 kcal/mol for the reaction barrier and a decrease of 5.6 kcal/mol
      for the reaction free energy, respectively. Combining the results of two previous
      calculation results on CHCl(3) + OH(-) and CH(2)Cl(2) + OH(-) reactions in water,
      we demonstrate that increase in the chlorination of the methyl group (from
      CH(3)Cl to CHCl(3)) is accompanied by the decrease in the free energy reaction
      barrier, with the CH(3)Cl + OH(-) having the largest barrier among the three
      reactions.

PMID- 21942377
TI  - Mind over matter: reappraising arousal improves cardiovascular and cognitive
      responses to stress.
AB  - Researchers have theorized that changing the way we think about our bodily
      responses can improve our physiological and cognitive reactions to stressful
      events. However, the underlying processes through which mental states improve
      downstream outcomes are not well understood. To this end, we examined whether
      reappraising stress-induced arousal could improve cardiovascular outcomes and
      decrease attentional bias for emotionally negative information. Participants were
      randomly assigned to either a reappraisal condition in which they were instructed
      to think about their physiological arousal during a stressful task as functional
      and adaptive, or to 1 of 2 control conditions: attention reorientation and no
      instructions. Relative to controls, participants instructed to reappraise their
      arousal exhibited more adaptive cardiovascular stress responses-increased cardiac
      efficiency and lower vascular resistance-and decreased attentional bias. Thus,
      reappraising arousal shows physiological and cognitive benefits. Implications for
      health and potential clinical applications are discussed.

PMID- 21942378
TI  - Reproducible fabrication of robust, renewable vertically aligned multiwalled
      carbon nanotube/epoxy composite electrodes.
AB  - We describe the reproducible fabrication of robust, vertically aligned
      multiwalled carbon nanotube (VACNT)/epoxy composite electrodes. The electrodes
      are characterized by cyclic voltammetry, impedance spectroscopy, and scanning
      electron and atomic force microscopies. Low background currents are obtained at
      the electrodes, and common redox probe molecules and NADH show excellent
      voltammetric behavior. When electrode performance deteriorates due to fouling,
      the electrode surfaces can be reproducibly renewed by mechanical polishing
      followed by O(2) plasma treatment. The electrochemical performance of the
      electrodes is maintained after more than 100 cycles of use and renewal.

PMID- 21942382
TI  - Density functional analysis of the spin exchange interactions and charge order
      patterns in the layered magnetic oxides YBaM2O5 (M = Mn, Fe, Co).
AB  - The spin and charge order phenomena of the layered magnetic oxides YBaM(2)O(5) (M
      = Mn, Fe, Co) were analyzed on the basis of density functional calculations. We
      evaluated the spin exchange interactions of YBaM(2)O(5) by performing energy
      mapping analysis based on density functional calculations to find why they
      undergo a three-dimensional magnetic ordering at high temperature. We estimated
      the relative stabilities of the checkerboard and stripe charge order patterns of
      YBaM(2)O(5) (M = Mn, Fe, Co) by optimizing their structures with density
      functional calculations to probe if the nature of the charge order pattern
      depends on whether their transition-metal ions are Jahn-Teller active.

PMID- 21942383
TI  - Quantification of tocopherols, tocotrienols, and gamma-oryzanol contents and
      their distribution in some commercial rice varieties in Taiwan.
AB  - The eight vitamin E isomers [alpha-, beta-, gamma-, and delta-tocopherols (T) and
      alpha-, beta-, gamma-, and delta-tocotrienols (T3)] and gamma-oryzanol are known
      to possess diverse biological activities. This study examined the contents of
      these compounds and their distribution in 16 commercial rice varieties in Taiwan.
      Results showed that the order of vitamin E, total T, total T3, and gamma-oryzanol
      contents was rice bran > brown rice > rice husk > polished rice. gamma-T3 was the
      highest vitamin E isomer present in all rice samples, while beta-T, beta-T3,
      delta-T, and delta-T3 were present in trace amounts. The Japonica varieties
      contained a higher total T, total T3, and gamma-oryzanol than the Indica
      varieties. They also have a higher level of alpha-T and alpha-T3 but a lower
      level of gamma-T and gamma-T3 than the Indica varieties. However, no obvious
      difference in total T, total T3, and gamma-oryzanol content was noted between
      black- and red-colored rice varieties.

PMID- 21942384
TI  - Thermochemistry and reaction paths in the oxidation reaction of benzoyl radical:
      C6H5C*(?O).
AB  - Alkyl substituted aromatics are present in fuels and in the environment because
      they are major intermediates in the oxidation or combustion of gasoline, jet, and
      other engine fuels. The major reaction pathways for oxidation of this class of
      molecules is through loss of a benzyl hydrogen atom on the alkyl group via
      abstraction reactions. One of the major intermediates in the combustion and
      atmospheric oxidation of the benzyl radicals is benzaldehyde, which rapidly loses
      the weakly bound aldehydic hydrogen to form a resonance stabilized benzoyl
      radical (C6H5C(*)?O). A detailed study of the thermochemistry of intermediates
      and the oxidation reaction paths of the benzoyl radical with dioxygen is
      presented in this study. Structures and enthalpies of formation for important
      stable species, intermediate radicals, and transition state structures resulting
      from the benzoyl radical +O2 association reaction are reported along with
      reaction paths and barriers. Enthalpies, DeltafH298(0), are calculated using ab
      initio (G3MP2B3) and density functional (DFT at B3LYP/6-311G(d,p)) calculations,
      group additivity (GA), and literature data. Bond energies on the benzoyl and
      benzoyl-peroxy systems are also reported and compared to hydrocarbon systems. The
      reaction of benzoyl with O2 has a number of low energy reaction channels that are
      not currently considered in either atmospheric chemistry or combustion models.
      The reaction paths include exothermic, chain branching reactions to a number of
      unsaturated oxygenated hydrocarbon intermediates along with formation of CO2. The
      initial reaction of the C6H5C(*)?O radical with O2 forms a chemically activated
      benzoyl peroxy radical with 37 kcal mol(-1) internal energy; this is
      significantly more energy than the 21 kcal mol(-1) involved in the benzyl or
      allyl + O2 systems. This deeper well results in a number of chemical activation
      reaction paths, leading to highly exothermic reactions to phenoxy radical + CO2
      products.

PMID- 21942385
TI  - Conservation of spin polarization during triplet-triplet energy transfer in
      reconstituted peridinin-chlorophyll-protein complexes.
AB  - Peridinin-chlorophyll-protein (PCP) complexes, where the N-terminal domain of
      native PCP from Amphidinium carterae has been reconstituted with different
      chlorophyll (Chl) species, have been investigated by time-resolved EPR in order
      to elucidate the details of the triplet-triplet energy transfer (TTET) mechanism.
      This spectroscopic approach exploits the concept of spin conservation during
      TTET, which leads to recognizable spin-polarization effects in the observed time
      resolved EPR spectra. The spin polarization produced at the acceptor site
      (peridinin) depends on the initial polarization of the donor (chlorophyll) and on
      the relative geometric arrangement of the donor-acceptor spin axes. A variation
      of the donor triplet state properties in terms of population probabilities or
      triplet spin axis directions, as produced by replacement of chlorophyll a (Chl a)
      with non-native chlorophyll species (ZnChl a and BacterioChl a) in the
      reconstituted complexes, is unambiguously reflected in the polarization pattern
      of the carotenoid triplet state. For the first time, in the present investigation
      spin-polarization conservation has been shown to occur among natural cofactors in
      protein complexes during the TTET process. Proving the validity of the assumption
      of spin conservation adopted in the EPR spectral analysis, the results reinforce
      the hypothesis that in PCP proteins peridinin 614, according to X-ray
      nomenclature (Hofmann, E.; et al. Science 1996, 272, 1788-1791), is the
      carotenoid of election in the photoprotection mechanism based on TTET.

PMID- 21942388
TI  - Removal of dissolved organic matter (DOM) from raw water by single-walled carbon
      nanotubes (SWCNTs).
AB  - Dissolved organic matter (DOM) in raw water is a precursor for the formation of
      disinfection by-products (DBPs) during chlorination at a water treatment plant in
      southern Taiwan. The presence of DOM also has a large impact on the behavior of
      nanoparticles. The adsorption kinetics of single-walled carbon nanotubes (SWCNTs)
      was investigated in the presence of DOM as a possible technique for the
      pretreatment of DBP precursors. pH, ionic strength and temperature are major
      factors in adsorption tests. Experimental results indicated that adsorption
      reached equilibrium after 120 min. Additionally, the adsorption capacity of
      SWCNTs increased with an increasing DOM concentration and decreased with an
      increasing ionic strength. The optimum adsorption model out of a selection
      including the Modified Freundlich equation, the Pseudo-first-order equation and
      Pesudo-second order equation, was the Modified Freundlich equation model. The
      intraparticle diffusion equation model was also examined. The adsorption process
      was controlled by pore diffusion that was confirmed by the fits of intra-particle
      diffusion model. The maximum adsorption capacity was 26.1-20.8 mg/g at 4 degrees
      C and 45 degrees C. Isotherm adsorption results demonstrated that the adsorption
      of DOM onto SWCNTs was favorable at a high initial DOM concentration and at low
      ionic strength, pH and temperature. These findings highlighted the importance of
      pretreatments and the presence of DOM on the adsorption behavior of
      nanomaterials.

PMID- 21942389
TI  - Decolorization of ammonium lignosulfonate with H(2)O(2)/Cu(II) heterogeneous
      catalyst.
AB  - The potential of ammonium lignosulfonate (ALS) decolorization and degradation in
      aqueous solution was studied in a heterogeneous system using hydrogen peroxide
      and a Cu (II)-chelating ion exchanger. This was based on acrylic copolymers
      functionalized with N,N dimethylamino propylamine (DMAPA) as a catalyst. In order
      to optimize the efficiency of the system, the influence of such process
      parameters like H(2)O(2) concentration, pH, contact time, temperature, ALS
      concentration and catalyst amount were evaluated. The apparent rate constant of
      decolorization calculated from the absorbance data indicates that the process
      profiles follow pseudo-first order kinetics. Lignosulfonate degradation was
      furthermore studied by FTIR spectroscopy, thermogravimetric analysis and
      determination in phenolic compounds. The catalyst stability and reusability have
      also been investigated. Our experimental results clearly indicate that, under
      optimum conditions, the ammonium lignosulfonate solutions exhibit a total
      bleaching associated with degradation and significant mineralization to CO(2).

PMID- 21942390
TI  - Applicability of poorly crystalline aluminum oxide for adsorption of arsenate.
AB  - This study examined the characteristics of arsenate adsorption on poorly
      crystalline oxide (PCAO) which was obtained from recycling of dry sanding powders
      (DSP) produced during sanding and sawing process in a decorative interior
      company. After calcinating DSP at 550 degrees C, poorly crystalline oxide (PCAO)
      was obtained as an adsorbent. From the batch adsorption experiments, arsenate was
      completely removed up to the concentration of 10 mg/L by PCAO. The stability of
      PCAO as an adsorbent was evaluated at pH 7 and found that the arsenate adsorbed
      on PCAO was stable for 24 h. The predominant interaction between arsenate and
      PCAO was thought to be a strong chemical bond by spectroscopic analysis. The
      arsenate adsorption behavior onto PCAO was satisfactorily simulated with MINEQL+,
      suggesting that arsenate formed inner-sphere complexes with the surface of PCAO
      by chemisorption. Meanwhile, the presence of competitive anions such as PO(4) (3
      ), SO(4) (2-) and CO(3) (2-) decreased somewhat the removal efficiency of
      arsenate and the effects of competing anions on the adsorption of arsenate were
      in the order of PO(4) (3-) > SO(4) (2-) > CO(3) (2-) under pH 6. The application
      of PCAO to the real mine drainage was also carried out. Although the adsorption
      of arsenic on the PCAO was slightly decreased rather than that removed from
      synthetic wastewater due to competitive sorption by multiple ions, it was
      possible to meet the national discharge standard limit with increasing adsorbent
      concentration.

PMID- 21942391
TI  - Nitrogen and phosphorus removal using a novel integrated system of natural
      zeolite and lime.
AB  - Nitrogen and phosphorus can cause eutrophication problems in receiving waters.
      These nutrients can be eliminated by different wastewater treatments but they
      tend to be costly or require complex operations. With these reasons in mind, this
      work set out to study the behavior of a novel combined or integrated system with
      zeolite and lime for the removal of these chemical species. With the integrated
      treatment, excellent removals-98 % NH(+) (4), 100 % total phosphorus (TP), 79 %
      chemical oxygen demand (COD), 71 % BOD(5), 99 % of total suspended solids (TSS)
      and 100 % of fecal coliforms-were obtained. A sludge production of 4.4 % and 4.8
      % of the wastewater total volume treated with lime was achieved. The final liquid
      effluent of the integrated system of natural zeolite and lime had a composition
      which was suitable for its discharge into sewerage systems and marine or
      continental waters (according to Chilean regulations), as far as the
      concentrations of nitrogen, phosphorus and total coliforms were concerned.
      Validated curves with their corresponding equations were obtained in this study
      for the removal of ammonia nitrogen and total phosphorus. These equations can
      theoretically be applied to estimate the removal of both parameters in studies or
      practical applications undertaken with operating conditions similar to those used
      in this work.

PMID- 21942392
TI  - Comparative prediction schemes using conventional and advanced statistical
      analysis to predict microbial water quality in runoff from manured fields.
AB  - Accurate estimations of indicator microorganisms' concentrations are necessary to
      properly monitor water quality and manage contamination from agricultural land
      runoffs. In this study, Artificial Neural Networks (ANNs) and Multiple Regression
      Analysis (MRA) statistical methods were compared for accuracy in the prediction
      of manure-borne microorganisms' concentrations in runoffs from agricultural plots
      (0.75 m * 2 m) treated with cattle or swine manure. Field rainfall simulation
      tests were initiated on days 4, 32, 62, 123, and 354 between June 2002 and May
      2003. Each rainfall event produced 35 mm rainfall for 30 min at the intensity of
      70 mm hr(-1) at 24-intervals. Concentrations of microbial indicators were
      correlated with hydrological and environmental water quality parameters including
      water runoff, erosion, air temperature, relative humidity, solar radiation, pH,
      electric conductivity (EC) and turbidity to determine their impacts on microbial
      fate and transport. ANNs demonstrated a better ability to model the nonlinearity
      of land application of manure to ensure the safety of agricultural water
      environments.

PMID- 21942393
TI  - Algae utilization in assessment of the large Turawa Lake (Poland) pollution with
      heavy metals.
AB  - This investigation was undertaken to determine the applicability of algae for the
      assessment of contamination level of water reservoirs with heavy metals. The alga
      Spirogyra sp. collected in the littoral zone of the Large Turawa Lake (artificial
      lake in Southern Poland) was used for the study. The concentrations of heavy
      metals accumulated in the alga inhabiting a flow-through water basin of the Large
      Turawa Lake were found to correlate with sources of these metals, such as benthic
      sediments and contaminated watercourses. The highest concentrations of metals
      were found in alga samples collected at the outlet of the lake: c (Mn) = 12330
      mg/kg dry mass, c (Fe) = 15059 mg/kg d.m., c (Cu) = 47.5 mg/kg d.m., c (Zn) =
      1411 mg/kg d.m., c (Cd) = 108.8 mg/kg d.m., and c (Pb) = 684 mg/kg d.m. The
      metals originated from benthic sediments (sapropelic mud) deposited close to the
      outlet of the lake. Statistically significant differences in the concentrations
      of cadmium accumulated in the alga were found between samples from the sites,
      where cadmium occurred in sandy sediments (max. 27.6 mg/kg d.m.), and samples
      from the sites located far from the contaminated sediments (max. 12.8 mg/kg
      d.m.).

PMID- 21942395
TI  - In vitro effects of radiofrequency electromagnetic waves on bovine spermatozoa
      motility.
AB  - In this study the effects of 1800 MHz GSM-like radiofrequency electromagnetic
      waves (RF-EMW) exposure on bovine semen was monitored. The experimental samples
      were analyzed in vitro in four time periods (0, 30, 120 and 420 min) and compared
      with unexposed samples (control). Spermatozoa motility was determined by computer
      assisted semen analyzer (CASA). Evaluation of the percentage of motile
      spermatozoa showed significant (P < 0.001) decrease in experimental groups after
      120 and 420 min of culture when exposed to microwaves, in comparison to control.
      Similar spermatozoa motility inhibition was detected for the percentage of
      progressively motile spermatozoa, too. Average path distance decreased
      significantly (p < 0.001) in experimental groups after 30 and 420 min of culture.
      Path velocity increased in the experimental groups exposed to RF-EMW after 30
      minutes of culture, but subsequently decreased after 420 min of culture, in
      comparison to control. This indicates a possible initial stimulation and
      subsequent velocity inhibition of bovine spermatozoa under RF-EMW exposure.
      Changes in spermatozoa motility were also detected for some fine parameters, too.
      A significant decrease (P < 0.001) was noted for amplitude of lateral head
      displacement in the experimental group after 420 minutes of culture. Detailed in
      vitro motility analysis of bovine spermatozoa exposed to microwave radiation
      suggested that the parameters of path and velocity at the beginning of the
      culture significantly increase, but after longer culture (420 minutes) a
      significant decrease occur in the experimental group as compared to control. In
      general, results of this experiment indicate a negative time-dependent effect of
      1800 MHz RF-EMW radiation on bovine spermatozoa motility.

PMID- 21942394
TI  - Feasibility of sunflower oil cake degradation with three different anaerobic
      consortia.
AB  - Sunflower oil cake (SuOC) is the solid by-product from the sunflower oil
      extraction process and an important pollutant waste because of its high organic
      content. For the anaerobic digestion of SuOC three different industrial reactors
      were compared as inoculum sources. This was done using a biochemical methane
      production (BMP) test. Inoculum I was a granular biomass from an industrial
      reactor treating soft-drink wastewaters. Inoculum II was a flocculent biomass
      from a full-scale reactor treating biosolids generated in an urban wastewater
      treatment plant. Inoculum III was a granular biomass from an industrial reactor
      treating brewery wastes. The highest kinetic constant for methane production was
      achieved using inoculum II. The inoculum sources were analyzed through PCR
      amplification of 16S rRNA genes and fingerprinting before (t = 0) and after the
      BMP test (t = 12 days). No significant differences were found in the bacterial
      community fingerprints between the beginning and the end of the experiments. The
      bacterial and archaeal communities of inoculum II were further analyzed. The main
      bacteria found in this inoculum belong to Alphaproteobacteria and Chloroflexi. Of
      the Archaea detected, Methanomicrobiales and Methanosarcinales made up
      practically the whole archaeal community. The results showed the importance of
      selecting an appropriate inoculum in short term processes due to the fact that
      the major microbial constituents in the initial consortia remained stable
      throughout anaerobic digestion.

PMID- 21942396
TI  - Biofuel: an alternative to fossil fuel for alleviating world energy and economic
      crises.
AB  - The time has come when it is desirable to look for alternative energy resources
      to confront the global energy crisis. Consideration of the increasing
      environmental problems and the possible crisis of fossil fuel availability at
      record high prices dictate that some changes will need to occur sooner rather
      than later. The recent oil spill in the Gulf of Mexico is just another example of
      the environmental threats that fossil fuels pose. This paper is an attempt to
      explore various bio-resources such as corn, barley, oat, rice, wheat, sorghum,
      sugar, safflower, and coniferous and non-coniferous species for the production of
      biofuels (ethanol and biodiesel). In order to assess the potential production of
      biofuel, in this paper, countries are organized into three groups based on: (a)
      geographic areas; (b) economic development; and(c) lending types, as classified
      by the World Bank. First, the total fossil fuel energy consumption and supply and
      possible carbon emission from burning fossil fuel is projected for these three
      groups of countries. Second, the possibility of production of biofuel from grains
      and vegetative product is projected. Third, a comparison of fossil fuel and
      biofuel is done to examine energy sustainability issues.

PMID- 21942397
TI  - Growth of  Esteya vermicola  in media amended with nitrogen sources yields
      conidia with increased predacity and resistance to environmental stress.
AB  - Esteya vermicola , an endoparasitic fungus of pinewood nematode, exhibits great
      potential as a biological agent against nematodes. In this study to enhance the
      sporulation, predacity, and environmental resistance of E. vermicola, various
      nitrogen sources, such as glycine, L-leucine, and ammonium nitrate, were tested.
      The supplement of glycine and L-leucine had a significant influence on the growth
      rate of the colony, enhancing colony dry mass by 5-fold more than did ammonium
      nitrate or the control. Of the nitrogen sources tested, ammonium nitrate and L
      leucine promoted sporulation, yielding more than 6 * 10(6) CFU/g, while glycine
      enhanced the proportion of lunate spores. Meanwhile, the supplement of nitrogen
      sources had a significant influence on adhesive rate and mortality rate against
      Bursaphelenchus xylophilus . Moreover, the supplement of glycine enhanced the
      survival rate against heat stress by more than 3-fold that of L-leucine, ammonium
      nitrate, and control. The spores produced in media amended with glycine, L
      leucine, and ammonium nitrate had slightly but not significantly higher UV
      resistance and drought resistance than spores produced without nitrogen sources.
      These results suggested that the addition of glycine resulted in the production
      of E. vermicola conidia with increased predacity and resistance to environmental
      stress that may be more suitable for control of pine wilt disease.

PMID- 21942398
TI  - First-principles study of silicon nanowire approaching the bulk limit.
AB  - First-principles density functional theory calculations on hydrogenated silicon
      nanowires (SiNWs) with diameters up to 7.3 nm are carried out for comparing to
      experimentally relevant SiNWs and evaluating its radial doping profiles. We show
      that the direct band gap nature of both the small diameter (110) and (100) SiNWs
      fades when the diameter reaches beyond about 4 nm, where the difference of direct
      and indirect band gaps are close, within the experimental measurement uncertainty
      of +/-0.1 eV, suggesting the diameter size where the gap nature transition
      starts. In addition, we reveal that core-surface boron (B) codoped SiNW forms
      more preferably at large diameter than that of the surface-surface codoped one,
      attributing to the lower energy configuration raised by the core B dopant at
      large diameter SiNW. More importantly, the diameter for such a preferential
      transition increases as the doping concentration decreases. Our results
      rationalize photoluminescent measurements and radial doping distributions of
      SiNWs.

PMID- 21942399
TI  - Rehabilitation of a patient with mandibular resection using osteointegrated
      implants: a case report.
AB  - This case report details a 65-year-old male patient who underwent mandibular
      resection and radiotherapy as treatment for squamous cell carcinoma of the right
      mandible. The patient was rehabilitated with an implant-supported fixed partial
      denture and a maxillary occlusal ramp. The patient has been wearing his
      prosthesis for 2 years with no complaints. 

PMID- 21942400
TI  - A molecular genetic linkage map identifying the St and H subgenomes of Elymus
      (Poaceae: Triticeae) wheatgrass.
AB  - Elymus L. is the largest and most complex genus in the Triticeae tribe of grasses
      with approximately 150 polyploid perennial species occurring worldwide. We report
      here the first genetic linkage map for Elymus. Backcross mapping populations were
      created by crossing caespitose Elymus wawawaiensis (EW) (Snake River wheatgrass)
      and rhizomatous Elymus lanceolatus (EL) (thickspike wheatgrass) to produce F(1)
      interspecific hybrids that were then backcrossed to the same EL male to generate
      progeny with segregating phenotypes. EW and EL are both allotetraploid species (n
      = 14) containing the St (Pseudoroegneria) and H (Hordeum) genomes. A total of 387
      backcross progeny from four populations were genotyped using 399 AFLP and 116 EST
      based SSR and STS markers. The resulting consensus map was 2574 cM in length
      apportioned among the expected number of 14 linkage groups. EST-based SSR and STS
      markers with homology to rice genome sequences were used to identify Elymus
      linkage groups homoeologous to chromosomes 1-7 of wheat. The frequency of St
      derived genome markers on each linkage group was used to assign genome
      designations to all linkage groups, resulting in the identification of the seven
      St and seven H linkage groups of Elymus. This map also confirms the alloploidy
      and disomic chromosome pairing and segregation of Elymus and will be useful in
      identifying QTLs controlling perennial grass traits in this genus.

PMID- 21942402
TI  - Discontinued and alternative brominated flame retardants in the atmosphere and
      precipitation from the great lakes basin.
AB  - Air (vapor and particle) and precipitation samples were collected at five sites
      (two urban, one rural, and two remote) around the Great Lakes during 2005-2009 as
      a part of the Integrated Atmospheric Deposition Network (IADN). The
      concentrations of polybrominated diphenyl ethers (PBDEs), decabromodiphenylethane
      (DBDPE), hexabromobenzene (HBB), pentabromoethylbenzene (PBEB), and 1,2-bis(2,4,6
      tribromophenoxy)ethane (BTBPE) were measured in these samples. The highest
      concentrations of these compounds were generally observed at the two urban sites
      Chicago and Cleveland-with a few exceptions: The remote site at Eagle Harbor had
      particularly high levels of PBEB in all three phases, and the rural Sturgeon
      Point site had the highest HBB concentrations in the vapor phase. The sources of
      HBB and PBEB to these sites are unknown. A multiple linear regression model was
      applied to the concentrations of these compounds in the vapor phase, particle
      phase, precipitation, and the three phases combined. This regression resulted in
      overall (three phases combined) halving times for total PBDE concentrations of
      6.3 +/- 1.1 years. The overall halving times for HBB and BTBPE were 9.5 +/- 4.6
      years and 9.8 +/- 2.8 years, respectively. For PBEB and DBDPE, the regression was
      not statistically significant for the combined phases, indicating that the
      atmospheric concentrations of these compounds have not changed between 2005 and
      2009.

PMID- 21942403
TI  - Control of microfluidic flow in amphiphilic fabrics.
AB  - Woven textile fabrics were designed and constructed from hydrophilic and
      hydrophobic spun yarns to give planar substrates containing amphiphilic
      microchannels with defined orientations and locations. Polypropylene fibers were
      spun to give hydrophobic yarns, and the hydrophilic yarns were spun from a
      poly(ethylene terephthalate) copolyester. Water wicking rates into the fabrics
      were measured by video microscopy from single drops, relevant for point-of-care
      microfluidic diagnostic devices, and from reservoirs. intra-yarn microchannels in
      the hydrophilic polyester yarns were shown to selectively transport aqueous
      fluids, with the flow path governed by the placement of the hydrophilic yarns in
      the fabric. By comparing fluid transport in fabric constructions with systematic
      variations in the numbers of adjacent parallel and orthogonal hydrophilic yarns,
      it was found that inter-yarn microchannels significantly increased wicking rates.
      Simultaneous wicking of an aqueous and hydrocarbon fluid into the hydrophilic and
      hydrophobic microchannels of an amphiphilic fabric was successfully demonstrated.
      The high degree of interfacial contact and micrometer-scale diffusion lengths of
      such coflowing immiscible fluid streams inside amphiphilic fabrics suggest
      potential applications as highly scalable and affordable microcontactors for
      liquid-liquid extractions.

PMID- 21942404
TI  - Development of gold nanoparticle-based rapid detection kit for melamine in milk
      products.
AB  - A reliable and sensitive kit for the rapid detection of melamine (Mel) was
      developed. The kit is based on gold nanoparticle (Au NP) probe and includes a
      standard colorimetric card. The Au NPs were prepared by sodium borohydride
      reduction and characterized by transmission electron microscopy, which revealed
      particle sizes of approximately 5 nm. The performance of the kit in terms of
      aggregation kinetics, cross-reactivity, anti-interference, and sample
      pretreatment was investigated. The standard colorimetric card was then fabricated
      by chromatic aberration of a series of standard Mel-spiked milk reacts with the 5
      nm Au NPs. The working range of the kit is 1-120 mg/L, and its performance is
      visibly more rapid and reliable by comparison with the standard colorimetric
      card. As low as 1 mg/L of Mel levels in milk can be determined, with the assay
      taking only about 10 min, including sample pretreatment. The kit can be stored
      for a year at room temperature. Samples were also detected by the kit, yielding
      results close to those obtained by high-performance liquid chromatography/mass
      spectrometry. Thus, the kit is applicable to qualitative and semiquantitative
      field detection, as well as naked-eye screening without the aid of any
      instrumentation.

PMID- 21942407
TI  - Tainted visions: the effect of visionary leader behaviors and leader
      categorization tendencies on the financial performance of ethnically diverse
      teams.
AB  - Despite the increasing prevalence of ethnic diversity, findings regarding its
      effects on team performance remain contradictory. We suggest that past
      inconsistencies can be reconciled by examining the joint impact of leader
      behavior and leader categorization tendencies in ethnically diverse teams. We
      propose that leaders who exhibit high levels of visionary leader behavior and
      also have the tendency to categorize their team members into in- and out-groups
      will facilitate a negative effect of ethnic diversity on team communication and
      financial performance, whereas leaders who exhibit visionary behaviors but do not
      tend to categorize will lead ethnically diverse teams to positive outcomes. We
      find support for these ideas in a study of 100 retail outlets.

PMID- 21942405
TI  - Effects of resource-building group intervention on career management and mental
      health in work organizations: randomized controlled field trial.
AB  - A resource-building group intervention was developed to enhance career
      management, mental health, and job retention in work organizations. The in
      company training program provided employees with better preparedness to manage
      their own careers. The program activities were universally implemented using an
      organization-level, 2-trainer model with trainers from the human resources
      management and occupational health services. The study was a within
      organizations, randomly assigned field experimental study; it investigated the
      impacts of the intervention on immediate career management preparedness and later
      mental health and intentions to retire early. A total of 718 eligible individuals
      returned a questionnaire in 17 organizations and became voluntary participants.
      The respondents were randomly assigned to either an intervention (N = 369) or a
      comparison group (N = 349). Those in the intervention group were invited to group
      intervention workshops, whereas those in the comparison group received printed
      information about career and health-related issues. The 7-month follow-up results
      showed that the program significantly decreased depressive symptoms and
      intentions to retire early and increased mental resources among the group
      participants compared to the others. The mediation analyses demonstrated that the
      increase in career management preparedness as a proximal impact of the
      intervention mediated the longer term mental health effects. Those who benefited
      most from the intervention as regards their mental health were employees with
      elevated levels of depression or exhaustion and younger employees, implying
      additional benefits of a more targeted use of the intervention. The results
      demonstrated the benefits of the enhancement of individual-level career
      management and resilience resources as career and health promotion practice in
      work organizations.

PMID- 21942408
TI  - Longitudinal relationships between core self-evaluations and job satisfaction.
AB  - Core self-evaluations (CSE) have been proposed as a static personality trait that
      influences individuals' work experiences. However, CSE can also be influenced by
      work experiences. Based on the corresponsive principle of personality
      development, this study incorporated both dispositional and contextual
      perspectives to examine longitudinal reciprocal relationships between CSE and job
      satisfaction. Longitudinal data from 5,827 participants in the British Household
      Panel Survey from 1997 to 2006 were analyzed. A series of structural equation
      models revealed that job satisfaction and the growth of job satisfaction in
      previous years positively predicted CSE in a later year. In turn, CSE contributed
      to higher job satisfaction and growth of job satisfaction in following years.
      This result shows that both dispositional and contextual forces interweave to
      shape individuals' self-views and experiences over time.

PMID- 21942409
TI  - Spatially confined redox chemistry in periodic mesoporous hydridosilica
      nanosilver grown in reducing nanopores.
AB  - Periodic mesoporous hydridosilica, PMHS, is shown for the first time to function
      as both a host and a mild reducing agent toward noble metal ions. In this
      archetypical study, PMHS microspheres react with aqueous Ag(I) solutions to form
      Ag(0) nanoparticles housed in different pore locations of the mesostructure. The
      dominant reductive nucleation and growth process involves SiH groups located
      within the pore walls and yields molecular scale Ag(0) nanoclusters trapped and
      stabilized in the pore walls of the PMHS microspheres that emit orange-red
      photoluminescence. Lesser processes initiated with pore surface SiH groups
      produce some larger spherical and worm-shaped Ag(0) nanoparticles within the pore
      voids and on the outer surfaces of the PMHS microspheres. The intrinsic reducing
      power demonstrated in this work for the pore walls of PMHS speaks well for a new
      genre of chemistry that benefits from the mesoscopic confinement of Si-H groups.

PMID- 21942410
TI  - The fourth mammalian molybdenum enzyme mARC: current state of research.
AB  - The mitochondrial amidoxime-reducing component (mARC) is a recently discovered
      molybdenum-containing enzyme in mammalians. Upon reconstitution with the electron
      transport proteins, cytochrome b(5) and its reductase, this molybdenum enzyme is
      capable of reducing N-hydroxylated compounds. It was named mARC because the N
      reduction of amidoxime structures was initially studied using this isolated
      mitochondrial enzyme. All hitherto analyzed mammalian genomes harbor two mARC
      genes: molybdenum cofactor (Moco) sulferase C-terminal domain MOSC1 and MOSC2.
      Proteins encoded by these genes represent the simplest eukaryotic molybdenum
      enzymes, in that they bind only the Moco. It is also suggested that they are
      members of a new family of molybdenum enzymes. mARC and its N-reductive enzyme
      system plays a major role in drug metabolism, especially in the activation of so
      called "amidoxime-prodrugs" and in the detoxification of N-hydroxylated
      xenobiotics, though its physiological relevance is largely unknown.

PMID- 21942411
TI  - Connecting rare DNA conformations and surface dynamics using single-molecule
      resonance energy transfer.
AB  - A mechanistic understanding of single-stranded DNA (ssDNA) behavior in the near
      surface environment is critical to advancing DNA-directed self-assembled
      nanomaterials. A new approach is described that uses total internal reflection
      fluorescence microscopy to measure resonance energy transfer at the single
      molecule level, providing a mechanistic understanding of the connection between
      molecular conformation and interfacial dynamics near amine-modified surfaces.
      Large numbers (>10(5)) of ssDNA trajectories were observed, permitting dynamic
      correlation of molecular conformation with desorption and surface mobility. On
      the basis of dynamic behavior, molecules could be designated as members of the
      more common coiled population or a rare, weakly bound conformation. Molecules in
      the coiled state generally exhibited slow diffusion and conformational
      fluctuations that decreased with increasing average end-to-end distance. Lattice
      simulations of adsorbed self-avoiding polymers successfully predicted these
      trends. In contrast, the weakly bound conformation, observed in about 5% of
      molecules, had a large end-to-end distance but demonstrated conformational
      fluctuations that were much higher than predicted by simulations for adsorbed
      flexible chains. This conformation correlated positively with desorption events
      and led to fast diffusion, indicating weak surface associations. Understanding
      the role of the weakly bound conformation in DNA hybridization, and how solution
      conditions and surface properties may favor it, could lead to improved self
      assembled nanomaterials.

PMID- 21942412
TI  - Direct demonstration of tissue uptake of an inhaled drug: proof-of-principle
      study using matrix-assisted laser desorption ionization mass spectrometry
      imaging.
AB  - Drug therapy is often directed to specific organ and tissue compartments where
      the mode of action of the compound affects specifically targeted biological
      processes. However, the direct measurement of drug uptake in terms of a time
      kinetic and concentrations attained at the local sites has not been readily
      available as a clinical index for most drugs. A proof-of-principle study was
      conducted to test the utility of applying matrix-assisted laser desorption
      ionization-mass spectrometry imaging (MALDI-MSI) to demonstrate the qualitative
      distribution pattern of a locally administered drug within tissue sites of
      targeted action. Here we have measured the occurrence of an inhaled
      bronchodilator, the muscarinic receptor antagonist ipratropium, within human
      bronchial biopsies obtained by fiber optic bronchoscopy shortly after dosing
      exposure. Cryo-preserved biopsy samples from five subjects being evaluated for
      airway obstruction or potential tumor development were prepared as thin frozen
      sections. Samples coated with a MALDI matrix were analyzed by a MALDI LTQ
      Orbitrap XL mass spectrometer at large (100 MUm) and small (30 MUm) raster sizes.
      Our results demonstrate that ipratropium is rapidly absorbed into the airway
      wall. Ipratropium parent ion (m/z 332.332) and daughter ions (m/z 166.2 and
      290.2) were coincidently partitioned within submucosal spaces containing targeted
      airway smooth muscle in four out of five subjects. The signal intensity of
      ipratropium fragment ions provided estimates that local drug concentrations
      between 3 and 80 nM were achieved within the airway wall. To our knowledge, this
      is the first reported study in applying MALDI-MSI to demonstrate the localization
      of a drug administered at therapeutic levels. The study highlights the potential
      benefit of MALDI-MSI to provide important measurements of drug efficacy in
      clinical settings.

PMID- 21942413
TI  - Using engineered single-chain antibodies to correlate molecular binding
      properties and nanoparticle adhesion dynamics.
AB  - Elucidation of the relationship between targeting molecule binding properties and
      the adhesive behavior of therapeutic or diagnostic nanocarriers would aid in the
      design of optimized vectors and lead to improved efficacy. We measured the
      adhesion of 200-nm-diameter particles under fluid flow that was mediated by a
      diverse array of molecular interactions, including recombinant single-chain
      antibodies (scFvs), full antibodies, and the avidin/biotin interaction. Within
      the panel of scFvs, we used a family of mutants that display a spectrum of
      binding kinetics, allowing us to compare nanoparticle adhesion to bond chemistry.
      In addition, we explored the effect of molecular size by inserting a protein
      linker into the scFv fusion construct and by employing scFvs that are specific
      for targets with vastly different sizes. Using computational models, we extracted
      multivalent kinetic rate constants for particle attachment and detachment from
      the adhesion data and correlated the results to molecular binding properties. Our
      results indicate that the factors that increase encounter probability, such as
      adhesion molecule valency and size, directly enhance the rate of nanoparticle
      attachment. Bond kinetics had no influence on scFv-mediated nanoparticle
      attachment within the kinetic range tested, however, but did appear to affect
      antibody/antigen and avidin/biotin mediated adhesion. We attribute this finding
      to a combination of multivalent binding and differences in bond mechanical
      strength between recombinant scFvs and the other adhesion molecules. Nanoparticle
      detachment probability correlated directly with adhesion molecule valency and
      size, as well as the logarithm of the affinity for all molecules tested. On the
      basis of this work, scFvs can serve as viable targeting receptors for
      nanoparticles, but improvements to their bond mechanical strength would likely be
      required to fully exploit their tunable kinetic properties and maximize the
      adhesion efficiency of nanoparticles that bear them.

PMID- 21942418
TI  - The crossmodal facilitation of visual object representations by sound: evidence
      from the backward masking paradigm.
AB  - We report a series of experiments designed to demonstrate that the presentation
      of a sound can facilitate the identification of a concomitantly presented visual
      target letter in the backward masking paradigm. Two visual letters, serving as
      the target and its mask, were presented successively at various interstimulus
      intervals (ISIs). The results demonstrate that the crossmodal facilitation of
      participants' visual identification performance elicited by the presentation of a
      simultaneous sound occurs over a very narrow range of ISIs. This critical time
      window lies just beyond the interval needed for participants to differentiate the
      target and mask as constituting two distinct perceptual events (Experiment 1) and
      can be dissociated from any facilitation elicited by making the visual target
      physically brighter (Experiment 2). When the sound is presented at the same time
      as the mask, a facilitatory, rather than an inhibitory effect on visual target
      identification performance is still observed (Experiment 3). We further
      demonstrate that the crossmodal facilitation of the visual target by the sound
      depends on the establishment of a reliable temporally coincident relationship
      between the two stimuli (Experiment 4); however, by contrast, spatial coincidence
      is not necessary (Experiment 5). We suggest that when visual and auditory stimuli
      are always presented synchronously, a better-consolidated object representation
      is likely to be constructed (than that resulting from unimodal visual
      stimulation).

PMID- 21942419
TI  - Design of efficient ambipolar host materials for organic blue
      electrophosphorescence: theoretical characterization of hosts based on carbazole
      derivatives.
AB  - Density functional theory calculations were carried out to investigate the
      electronic structures of representative ambipolar hosts for blue
      electroluminescence, based on two carbazole end groups and meta-terphenyl (mTP)
      like bridges. The bridge molecular segments include mTP, 2,6-bisphenylpyridine,
      3,5-bisphenylpyridine, and 2,6-bisphenylpyrimidine. While the ionization
      potentials and electron affinities of these molecules are mainly determined by
      their hole- and electron-transport subunits, respectively, each subunit impacts
      the electronic properties of the other upon their binding, mainly in an inductive
      way. Importantly, the lowest triplet state of the hosts is determined to be
      confined into the mTP-like bridges since these are the subunits with lowest
      individual triplet energy. Extension of the phenyl-based pi-conjugated system via
      meta linkages is found to be effective in modulating the electron affinity value
      while maintaining a high triplet energy.

PMID- 21942421
TI  - Insights into dehydrogenative coupling of alcohols and amines catalyzed by a
      (PNN)-Ru(II) hydride complex: unusual metal-ligand cooperation.
AB  - Density functional theory calculations were performed to elucidate the mechanism
      of dehydrogenative coupling of primary alcohols and amines mediated by a PNN
      Ru(II) hydride complex (PNN = (2-(di-tert-butylphosphinomethyl)-6
      (diethylaminomethyl)pyridine)). A plausible reaction pathway was proposed which
      contains three stages: (1) The alcohol dehydrogenation reaction to generate the
      aldehyde and H(2); (2) The aldehyde-amine condensation reaction to form the
      hemiaminal intermediate; (3) The dehydrogenation process of the hemiaminal
      intermediate to yield the final amide product with the liberation of H(2). The
      first and third stages occur via a similar pathway: (a) Proton transfer from the
      substrate to the PNN ligand; (b) Intramolecular rearrangement of the deprotonated
      substrate to form an anagostic complex; (c) Hydride transfer from the
      deprotonated substrate to the Ru center to yield the trans-dihydride intermediate
      and the aldehyde (or amide); (d) Benzylic proton migration from the PNN ligand to
      the metal center forming a dihydrogen complex and subsequent H(2) liberation to
      regenerate the catalyst. In all these steps, the metal-ligand cooperation plays
      an essential role. In proton transfer steps (a) and (d), the metal-ligand
      cooperation is achieved through the aromatization/dearomatization processes of
      the PNN ligand. While in steps (b) and (c), their collaboration are demonstrated
      by the formation of an anagostic interaction between Ru and the C-H bond and two
      ionic hydrogen bonds supported by the PNN ligand.

PMID- 21942422
TI  - Soy isoflavones and other isoflavonoids activate the human bitter taste receptors
      hTAS2R14 and hTAS2R39.
AB  - The aim of this study was to identify the bitter receptor(s) that recognize the
      bitter taste of the soy isoflavone genistein. Screening of all 25 human bitter
      receptors revealed genistein as agonist of hTAS2R14 and hTAS2R39. Genistein
      displayed threshold values of 4 and 8 MUM on hTAS2R14 and hTAS2R39 and EC(50)
      values of 29 and 49 MUM, respectively. In addition, the behavior of structurally
      similar isoflavonoids was investigated. Although the two receptors are not
      closely related, the results for hTAS2R14 and hTAS2R39 were similar toward most
      isoflavonoid aglycones. By trend, threshold values were slightly lower on
      hTAS2R14. Glucosylation of isoflavones seemed to inhibit activation of hTAS2R14,
      whereas four of five glucosylated isoflavones were agonists of hTAS2R39, namely,
      glycitin, genistin, acetylgenistin, and malonylgenistin. A total of three
      hydroxyl substitutions of the A- and B-rings of the isoflavonoids seemed to be
      more favorable for receptor activation than fewer hydroxyl groups. The
      concentration of the trihydroxylated genistein in several soy foods exceeds the
      determined bitter receptor threshold values, whereas those of other soy
      isoflavones are around or below their respective threshold value. Despite its low
      concentration, genistein might be one of the main contributors to the bitterness
      of soy products. Furthermore, the bioactive isoflavonoids equol and coumestrol
      activated both receptors, indicating that their sensory impact should be
      considered when used as food ingredients.

PMID- 21942420
TI  - Cytokines in autoimmunity: role in induction, regulation, and treatment.
AB  - Cytokines play a pivotal role in the pathogenesis of autoimmune diseases. The
      precise triggers for the breakdown of self-tolerance and the subsequent events
      leading to the induction of pathogenic autoimmune responses remain to be defined
      for most of the naturally occurring autoimmune diseases. Studies conducted in
      experimental models of human autoimmune diseases and observations in patients
      have revealed a general scheme in which proinflammatory cytokines contribute to
      the initiation and propagation of autoimmune inflammation, whereas anti
      inflammatory cytokines facilitate the regression of inflammation and recovery
      from acute phase of the disease. This idea is embodied in the T helper (Th) 1/Th2
      paradigm, which over the past two decades has had a major influence on our
      thinking about the role of cytokines in autoimmunity. Interestingly, over the
      past decade, the interleukin (IL)-17/IL-23 axis has rapidly emerged as the new
      paradigm that has compelled us to critically re-examine the cytokine-driven
      immune events in the pathogenesis and treatment of autoimmunity. In this 2-volume
      special issue of the journal, leading experts have presented their research
      findings and viewpoints on the role of cytokines in the context of specific
      autoimmune diseases.

PMID- 21942423
TI  - Novel therapies for hepatitis C: insights from the structure of the virus.
AB  - For the first time since the discovery of the hepatitis C virus (HCV),
      therapeutic options for hepatitis C have expanded. Several agents directly
      effective against HCV are now in development, including both direct-acting
      antiviral agents (DAAs) and host cofactor inhibitors. DAAs have been developed to
      inhibit several HCV proteins, including the NS3/4A serine protease, the NS5B RNA
      polymerase, NS5A, and NS4B. Host cofactor inhibitors include, but are not limited
      to, cyclophilin inhibitors, miR122 antagonists, and statins. Development of these
      agents represents a major advance in HCV therapeutics. This review provides a
      guide to HCV drugs in various stages of development, including an introduction to
      their mechanism of action, state of clinical development, efficacy, and side
      effects.

PMID- 21942425
TI  - Reporter protein-targeted probes for magnetic resonance imaging.
AB  - Contrast agents for magnetic resonance imaging are frequently employed as
      experimental and clinical probes. Drawbacks include low signal sensitivity, fast
      clearance, and nonspecificity that limit efficacy in experimental imaging. In
      order to create a bioresponsive MR contrast agent, a series of four Gd(III)
      complexes targeted to the HaloTag reporter were designed and synthesized. HaloTag
      is unique among reporter proteins for its specificity, versatility, and the
      covalent interaction between substrate and protein. In similar systems, these
      properties produce prolonged in vivo lifetimes and extended imaging opportunities
      for contrast agents, longer rotational correlation times, and increases in
      relaxivity (r(1)) upon binding to the HaloTag protein. In this work we report a
      new MR contrast probe, 2CHTGd, which forms a covalent bond with its target
      protein and results in a dramatic increase in sensitivity. A 6-fold increase in
      r(1), from 3.8 to 22 mM(-1) s(-1), is observed upon 2CHTGd binding to the target
      protein. This probe was designed for use with the HaloTag protein system which
      allows for a variety of substrates (specific for MRI, florescence, or protein
      purification applications) to be used with the same reporter.

PMID- 21942424
TI  - New paradigms for HIV/AIDS vaccine development.
AB  - HIV-1 and its simian counterpart SIV have been exquisitely tailored by evolution
      to evade host immunity. By virtue of specific adaptations that thwart individual
      innate or adaptive immune mechanisms, and an overall replication strategy that
      provides for rapid establishment of a large, systemic viral population, capable
      of dynamic adaptation to almost all immune selection pressures, these viruses,
      once established, almost invariably stay one step ahead of the host's immune
      system, and in the vast majority of infected individuals, replicate indefinitely.
      Although many vaccine approaches tested to date have been able to enhance the
      magnitude of the immune responses to HIV/SIV infection, most of these responses,
      whether cellular or humoral, have largely failed to be both effectively antiviral
      and targeted to prevent the emergence of fully functional escape variants. Recent
      advances, however, have provided strong evidence that the initial stages of
      infection following mucosal transmission of these viruses are more vulnerable to
      immune intervention, and have led to the development of vaccine strategies that
      elicit responses able to effectively intervene in these early stages of
      infection, either preventing acquisition of infection or establishing early,
      stringent, and durable control. Here, we place HIV/AIDS vaccine development in
      the context of the basic immunobiology of HIV and SIV, review the evidence for
      their vulnerability to immune responses immediately after mucosal transmission,
      and discuss how this newly recognized vulnerability might be exploited for the
      development of an effective HIV/AIDS vaccine.

PMID- 21942426
TI  - Discovery of 1-amino-5H-pyrido[4,3-b]indol-4-carboxamide inhibitors of Janus
      kinase 2 (JAK2) for the treatment of myeloproliferative disorders.
AB  - The JAK-STAT pathway mediates signaling by cytokines, which control survival,
      proliferation, and differentiation of a variety of cells. In recent years, a
      single point mutation (V617F) in the tyrosine kinase JAK2 was found to be present
      with a high incidence in myeloproliferative disorders (MPDs). This mutation led
      to hyperactivation of JAK2, cytokine-independent signaling, and subsequent
      activation of downstream signaling networks. The genetic, biological, and
      physiological evidence suggests that JAK2 inhibitors could be effective in
      treating MPDs. De novo design efforts of new scaffolds identified 1-amino-5H
      pyrido[4,3-b]indol-4-carboxamides as a new viable lead series. Subsequent
      optimization of cell potency, metabolic stability, and off-target activities of
      the leads led to the discovery of 7-(2-aminopyrimidin-5-yl)-1-{[(1R)-1
      cyclopropyl-2,2,2-trifluoroethyl]amino}-5H-pyrido[4,3-b]indole-4-carboxamide
      (65). Compound 65 is a potent, orally active inhibitor of JAK2 with excellent
      selectivity, PK profile, and in vivo efficacy in animal models.

PMID- 21942427
TI  - Enhancing the supercapacitor performance of graphene/MnO2 nanostructured
      electrodes by conductive wrapping.
AB  - MnO2 is considered one of the most promising pseudocapactive materials for high
      performance supercapacitors given its high theoretical specific capacitance, low
      cost, environmental benignity, and natural abundance. However, MnO2 electrodes
      often suffer from poor electronic and ionic conductivities, resulting in their
      limited performance in power density and cycling. Here we developed a "conductive
      wrapping" method to greatly improve the supercapacitor performance of
      graphene/MnO2-based nanostructured electrodes. By three-dimensional (3D)
      conductive wrapping of graphene/MnO2 nanostructures with carbon nanotubes or
      conducting polymer, specific capacitance of the electrodes (considering total
      mass of active materials) has substantially increased by ~20% and ~45%,
      respectively, with values as high as ~380 F/g achieved. Moreover, these ternary
      composite electrodes have also exhibited excellent cycling performance with >95%
      capacitance retention over 3000 cycles. This 3D conductive wrapping approach
      represents an exciting direction for enhancing the device performance of metal
      oxide-based electrochemical supercapacitors and can be generalized for designing
      next-generation high-performance energy storage devices.

PMID- 21942428
TI  - Discovery and description of the "davtiani" morphotype for Teladorsagia
      boreoarcticus (Trichostrongyloidea: Ostertagiinae) abomasal parasites in
      muskoxen, Ovibos moschatus, and caribou, Rangifer tarandus, from the North
      American Arctic: implications for parasite faunal diversity.
AB  - Collections to explore helminth diversity among free-ranging ungulates in the
      North American Arctic revealed the occurrence of a third male, or " davtiani ,"
      morphotype for Teladorsagia boreoarcticus . Designated as T. boreoarcticus forma
      (f.) minor B, the males occurred with T. boreoarcticus f. major and T.
      borearcticus f. minor A in endemic populations of muskoxen (Ovibos moschatus
      wardi) and barrenground caribou (Rangifer tarandus groenlandicus) on Victoria
      Island, Nunavut, Canada, and in muskoxen and Peary caribou ( Rangifer tarandus
      pearyi ) on Banks Island, Northwest Territories, Canada. These specimens differ
      from conspecific morphotypes in the structure of the genital cone and Sjoberg's
      organ. Relative to T. boreoarcticus f. minor A, specimens of T. boreoarcticus f.
      minor B are consistently smaller, and mean dimensions for the bursa and spicules
      do not overlap. The robust spicules are similar in form, particularly in the
      relative length of the dorsal and ventral processes, but mean total length is
      substantially less in specimens of T. boreoarcticus f. minor B. Differences that
      distinguish the minor morphotypes of T. boreoarcticus parallel those demonstrated
      for the T. trifurcata and T. davtiani morphotypes in association with T.
      circumcincta sensu stricto. New host and geographic records include the 3
      morphotypes of T. boreoarcticus in muskoxen and Peary caribou from Banks Island
      and in barrenground caribou from Victoria Island. Recognition of the ubiquitous
      nature of cryptic species emphasizes the need to effectively develop and use our
      collections-based resources and museum archives to build a robust understanding
      of the biosphere. Field inventory should include provisions for integrative
      approaches that preserve specimens suitable for comparative morphology, multi
      faceted molecular investigations, and population genetics.

PMID- 21942429
TI  - Infrared spectroscopy and molecular simulations of a polymeric sorbent and its
      enantioselective interactions with benzoin enantiomers.
AB  - Retention factors, k(R) and k(S), and enantioselectivities, S = k(R)/k(S), of
      amylose tris[(S)-alpha-methylbenzylcarbamate] (AS) sorbent for benzoin (B)
      enantiomers were measured for various isopropyl alcohol (IPA)/n-hexane
      compositions of the high-performance liquid chromatography (HPLC) mobile phase.
      Novel data for pure n-hexane show that k(R) = 106, k(S) = 49.6, and S = 2.13.
      With some IPA from 0.5 to 10 vol %, with S = 1.8-1.4, the retention factors were
      smaller. Infrared spectra showed evidence of substantial hydrogen bonding (H
      bonding) interactions in the pure polymer phase and additional H-bonding
      interactions between AS and benzoin. Density functional theory (DFT) was used to
      model the chain-chain and chain-benzoin H-bonding and other interactions. DFT was
      also used to predict fairly well the IR wavenumber shifts caused by the H-bonds.
      DFT simulations of IR bands of NH and C?O allowed for the first time the
      predictions of relative intensities and relative populations of H-bonding
      strengths. Molecular dynamics (MD) simulations were used to model a single 12-mer
      polymer chain. MD simulations predicted the existence of various potentially
      enantioselective cavities, two of which are sufficiently large to accommodate a
      benzoin molecule. Then "docking" studies of benzoin in AS with MD, Monte Carlo
      (MC), and MC/MD simulations were done to probe the AS-B interactions. The
      observed enantioselectivities are predicted to be primarily due to two H-bonds,
      of the kind AS CO...HO (R)-benzoin and AS NH...OC (R)-benzoin, and two pi-pi
      (phenyl-phenyl) interactions for (R)-benzoin and one H-bond, of type AS CO...HO
      (S)-benzoin, and one pi-pi interaction for (S)-benzoin. The MC/MD predictions are
      consistent with the HPLC and IR results.

PMID- 21942430
TI  - Darwin's legacy: why biology is not physics, or why evolution has not become a
      common sense.
AB  - Cosmology and evolution together have enabled us to look deep into the past and
      comprehend evolution-from the big bang to the cosmos, from molecules to humans.
      Here, I compare the nature of theories in biology and physics and ask why
      physical theories get accepted by the public without necessarily comprehending
      them but biological theories do not. Darwin's theory of natural selection,
      utterly simple in its premises but profound in its consequences, is not accepted
      widely. Organized religions, and creationists in particularly, have been the
      major critic of evolution, but not all opposition to evolution comes from
      organized religions. A great many people, between evolutionary biologists on one
      hand and creationists on the other, many academics included, who may not be
      logically opposed to evolution nevertheless do not accept it. This is because the
      process of and the evidence for evolution are invisible to a nonspecialist, or
      the theory may look too simple to explain complex traits to some, or because
      people compare evolution against God and find evolutionary explanations
      threatening to their beliefs. Considering how evolution affects our lives,
      including health and the environment to give just two examples, a basic course in
      evolution should become a required component of all our college and university
      educational systems.

PMID- 21942431
TI  - Estradiol-dependent modulation of serotonergic markers in auditory areas of a
      seasonally breeding songbird.
AB  - Because no organism lives in an unchanging environment, sensory processes must
      remain plastic so that in any context, they emphasize the most relevant signals.
      As the behavioral relevance of sociosexual signals changes along with
      reproductive state, the perception of those signals is altered by reproductive
      hormones such as estradiol (E2). We showed previously that in white-throated
      sparrows, immediate early gene responses in the auditory pathway of females are
      selective for conspecific male song only when plasma E2 is elevated to breeding
      typical levels. In this study, we looked for evidence that E2-dependent
      modulation of auditory responses is mediated by serotonergic systems. In female
      nonbreeding white-throated sparrows treated with E2, the density of fibers
      immunoreactive for serotonin transporter innervating the auditory midbrain and
      rostral auditory forebrain increased compared with controls. E2 treatment also
      increased the concentration of the serotonin metabolite 5-HIAA in the caudomedial
      mesopallium of the auditory forebrain. In a second experiment, females exposed to
      30 min of conspecific male song had higher levels of 5-HIAA in the caudomedial
      nidopallium of the auditory forebrain than birds not exposed to song. Overall, we
      show that in this seasonal breeder, (a) serotonergic fibers innervate auditory
      areas; (b) the density of those fibers is higher in females with breeding-typical
      levels of E2 than in nonbreeding, untreated females; and (c) serotonin is
      released in the auditory forebrain within minutes in response to conspecific
      vocalizations. Our results are consistent with the hypothesis that E2 acts via
      serotonin systems to alter auditory processing.

PMID- 21942432
TI  - Exploration of cerebellar-dependent associative learning in schizophrenia:
      effects of varying and shifting interstimulus interval on eyeblink conditioning.
AB  - Eyeblink conditioning abnormalities have been reported in schizophrenia, but the
      extent to which these anomalies are evident across a range of delay intervals
      (i.e., interstimulus intervals; ISIs) is unknown. In addition, the effects of ISI
      shifts on learning are unknown, though such manipulations can be informative
      about the plasticity of cerebellar timing functions. Therefore, the primary
      purpose of the present study was to investigate the interactions between ISI
      manipulations and learning in schizophrenia. A standard delay eyeblink
      conditioning procedure with four different interstimulus intervals (ISIs; 250,
      350, 550, 850 ms) was employed. Each eyeblink conditioning experiment was
      immediately followed by another with a different ISI, thus permitting the
      characterization of conditioned response (CR) learning at one ISI and the extent
      to which CRs could be generated at a different latency following an ISI shift.
      Collapsing across all conditions, the schizophrenia group (n = 55) had
      significantly fewer conditioned responses and longer onset latencies than age
      matched controls (n = 55). Surprisingly, shifting to a new ISI had negligible
      effects on conditioned response rates in both groups. These findings contribute
      to evidence of robust eyeblink conditioning abnormalities in schizophrenia and
      suggest impaired cerebellar function, but underscore the need for more research
      to clarify the source of these abnormalities and their relationship to clinical
      manifestations of schizophrenia.

PMID- 21942433
TI  - Effects of cortical and striatal dopamine D1 receptor blockade on cued versus
      noncued behavioral responses.
AB  - Various lines of evidence suggest that disruptions in brain dopamine (DA)
      transmission produce behavioral impairments that can be overcome by salient
      response-eliciting environmental stimuli. We examined here whether D1 receptor
      blockade within striatal or frontal cortical DA target regions would
      differentially affect head entry responses elicited by an auditory cue compared
      with those occurring during noncued intertrial intervals. Rats received 2 drug
      free 28-trial daily sessions in which an auditory cue was immediately followed by
      food delivery. On the following day, separate groups of rats received bilateral
      infusions of D1 antagonist SCH23390 to the dorsomedial striatum (DMS), nucleus
      accumbens (NAcc) core, or the medial prefrontal cortex (mPFC). SCH23390 infused
      into the DMS and NAcc core suppressed noncued head entries but had no effect on
      head entries in response to the auditory cue. SCH23390 infused to the mPFC did
      not reduce either cued or noncued approach responses. Systemic administration of
      the drug, in contrast, reduced the frequency of both cued and noncued approaches.
      The results are consistent with the notion that has emerged from the Parkinson's
      literature that reduced DA transmission produces behavioral suppression that can
      be overcome by salient environmental response elicitors, and extends this notion
      by showing that D1 receptor transmission within the striatum strongly suppresses
      noncued responses while leaving the identical behavior intact when cued by an
      environmental stimulus.

PMID- 21942434
TI  - theta-burst stimulation of the right neocerebellar vermis selectively disrupts
      the practice-induced acceleration of lexical decisions.
AB  - The present study reports an experiment of cerebellar transcranial magnetic
      stimulation in a lexical decision task. In contrast to the study by Argyropoulos
      (2011), no effect of cerebellar stimulation was observed on priming sizes.
      However, when subjects confronted the same stimuli in the second session of
      participation, lexical decision latencies did not become any shorter after
      stimulation of the right neocerebellar vermis, in contrast to all other
      conditions. This finding is discussed in the light of current research in
      cerebellar cognitive and linguistic functions, and provides some first evidence
      for the recently entertained hypothesis that neocerebellar loci are significant
      in acquiring, storing, and retrieving associative memory traces of repeatedly co
      occurring neural events in the language domain.

PMID- 21942435
TI  - Dose-dependent effects of hydrocortisone infusion on autobiographical memory
      recall.
AB  - The glucocorticoid hormone cortisol has been shown to impair episodic memory
      performance. The present study examined the effect of two doses of hydrocortisone
      (synthetic cortisol) administration on autobiographical memory retrieval. Healthy
      volunteers (n = 66) were studied on two separate visits, during which they
      received placebo and either moderate-dose (0.15 mg/kg IV; n = 33) or high-dose
      (0.45 mg/kg IV; n = 33) hydrocortisone infusion. From 75 to 150 min post-infusion
      subjects performed an Autobiographical Memory Test and the California Verbal
      Learning Test (CVLT). The high-dose hydrocortisone administration reduced the
      percent of specific memories recalled (p = .04), increased the percent of
      categorical (nonspecific) memories recalled (p < .001), and slowed response times
      for categorical memories (p < .001), compared with placebo performance. Under
      moderate-dose hydrocortisone the autobiographical memory performance did not
      change significantly with respect to percent of specific or categorical memories
      recalled or reaction times. Performance on the CVLT was not affected by
      hydrocortisone. These findings suggest that cortisol affects accessibility of
      autobiographical memories in a dose-dependent manner. Specifically,
      administration of hydrocortisone at doses analogous to those achieved under
      severe psychosocial stress impaired the specificity and speed of retrieval of
      autobiographical memories.

PMID- 21942436
TI  - Administration of dehydroepiandrosterone (DHEA) enhances visual-spatial
      performance in postmenopausal women.
AB  - The current article examines the effect of administering dehydroepiandrosterone
      (DHEA) on visual-spatial performance in postmenopausal women (N = 24, ages 55
      80). The concurrent reduction of serum DHEA levels and visual-spatial performance
      in this population, coupled with the documented effects of DHEA's androgenic
      metabolites on visual-spatial performance, suggests that DHEA administration may
      enhance visual-spatial performance. The current experiment used a double-blind,
      placebo-controlled crossover design in which 50 mg of oral DHEA was administered
      daily in the drug condition to explore this hypothesis. Performance on the Mental
      Rotation, Subject-Ordered Pointing, Fragmented Picture Identification, Perceptual
      Identification, Same-Different Judgment, and Visual Search tasks and serum levels
      of DHEA, DHEAS, testosterone, estrone, and cortisol were measured in the DHEA and
      placebo conditions. In contrast to prior experiments using the current
      methodology that did not demonstrate effects of DHEA administration on episodic
      and short-term memory tasks, the current experiment demonstrated large beneficial
      effects of DHEA administration on Mental Rotation, Subject-Ordered Pointing,
      Fragmented Picture Identification, Perceptual Identification, and Same-Different
      Judgment. Moreover, DHEA administration enhanced serum levels of DHEA, DHEAS,
      testosterone, and estrone, and regression analyses demonstrated that levels of
      DHEA and its metabolites were positively related to cognitive performance on the
      visual-spatial tasks in the DHEA condition.

PMID- 21942437
TI  - Comparative effects of different test day challenges on performance in the 5
      choice serial reaction time task.
AB  - The 5-choice serial reaction time task (5-CSRTT) is a valuable cognitive test
      that permits the simultaneous assessment of several different cognitive
      modalities, including attention, impulse control, processing speed, and cognitive
      flexibility. Increasing task difficulty on test days through various challenges
      can further enhance the versatility of this test by selectively enhancing the
      cognitive load on different aspects of the task. Systematic comparisons of the
      effects of different test day challenges on 5-CSRTT performance are essential to
      verify how these challenges affect different task measures and which
      manipulations are best suited for future studies of different aspects of
      cognition. We trained Wistar rats in the 5-CSRTT under standard conditions, then
      challenged them on the test days by (1) decreasing the duration of the stimulus
      to be detected, (2) increasing the time interval between trials (intertrial
      interval, ITI), (3) randomly varying the ITI, or (4) adding a flashing light
      distractor. All test day challenges produced distinct profiles of performance
      disruption that reflected differential effects on different cognitive modalities.
      Decreased stimulus duration selectively impaired attentional performance, while
      increased ITI increased impulsive-like premature responses and decreased trials
      completed. Variable ITI induced only mild, nonsignificant disruptions in response
      inhibition and processing speed, while the flashing light distractor produced
      comprehensive impairment affecting multiple aspects of 5-CSRTT performance,
      including disrupted attention and increased premature and timeout responses. This
      improved understanding of the effects of different test day challenges in the 5
      CSRTT will allow researchers to use these manipulations of a valuable cognitive
      test to their full potential.

PMID- 21942438
TI  - The modulation of fragile X behaviors by the muscarinic M4 antagonist,
      tropicamide.
AB  - Muscarinic acetylcholine receptors (mAChR) are G protein-coupled receptors (M1
      M5), grouped together into two functional classes, based on their G protein
      interaction. Although ubiquitously expressed in the CNS, the M4 protein shows
      highest expression in the neostriatum, cortex, and hippocampus.
      Electrophysiological and biochemical studies have provided evidence for
      overactive mAChR signaling in the fragile X knock-out (Fmr1KO) mouse model, and
      this has been hypothesized to contribute to the phenotypes seen in Fmr1KO mice.
      To address this hypothesis we used an M4 antagonist, tropicamide, to reduce the
      activity through the M4 mAChR and investigated the behavioral response in the
      Fmr1KO animals. Data from the marble-burying assay have shown that tropicamide
      treatment resulted in a decreased number of marbles buried in the wild-type (WT)
      and in the knockout (KO) animals. Results from the open field assay indicated
      that tropicamide increases activity in both the WT and KO mice. In the passive
      avoidance assay, tropicamide treatment resulted in the improvement of performance
      in both the WT and the KO animals at the lower doses (2 and 5 mg/kg), and the
      drug was shown to be important for the acquisition and not the consolidation
      process. Lastly, we observed that tropicamide causes a significant decrease in
      the percentage of audiogenic seizures in the Fmr1KO animals. These results
      suggest that pharmacological antagonism of the M4 receptor modulates select
      behavioral responses in the Fmr1KO mice.

PMID- 21942439
TI  - Similarities and differences in spatial learning and object recognition between
      young male C57Bl/6J mice and Sprague-Dawley rats.
AB  - Mice and rats are often used interchangeably in neuroscience research. However,
      species differences in brain structure and connectivity exist within the medial
      temporal lobe circuits that contribute to learning and memory. The hippocampus in
      particular contributes to both spatial learning and recognition memory, but the
      extent to which rats and mice are comparable in these two cognitive domains
      remains unclear. To evaluate potential species differences in spatial memory and
      object recognition, young adult male Sprague-Dawley rats and male C57Bl/6J mice
      were tested in the water maze and novel object recognition tasks. Following six
      days of training, with four trials per day, there was no difference in the
      ability of rats and mice to learn the location of a hidden platform. However,
      rats performed better than mice on the probe trial, indicative of superior
      retention. In the novel object preference test, no species differences in
      recognition memory were detected, although rats spent more time exploring the
      arena and took longer to approach the objects. These observations suggest that
      while species differences in spatial memory retention are present, they do not
      correlate with differences in object recognition memory.

PMID- 21942440
TI  - Amperometric detection of L-lactate using nitrogen-doped carbon nanotubes
      modified with lactate oxidase.
AB  - Nitrogen-doped carbon nanotubes (N-CNTs) provide a simple, robust, and unique
      platform for biosensing. Their catalytic activity toward the oxygen reduction
      reaction (ORR) and subsequent hydrogen peroxide (H(2)O(2)) disproportionation
      creates a sensitive electrochemical response to enzymatically generated H(2)O(2)
      on the N-CNT surface, eliminating the need for additional peroxidases or electron
      transfer mediators. Glassy carbon electrodes were modified with 7.4 atom % N
      CNTs, lactate oxidase (LOx), and a tetrabutylammonium bromide (TBABr)-modified
      Nafion binder. The resulting amperometric l-lactate biosensors displayed a
      sensitivity of 0.040 +/- 0.002 A M(-1) cm(-2), a low operating potential of -0.23
      V (vs Hg/Hg(2)SO(4)), a repeatability of 1.6% relative standard deviation (RSD)
      for 200 MUM samples of lactate, a fabrication reproducibility of 5.0% (RSD), a
      limit of detection of 4.1 +/- 1.6 MUM, and a linear range of 14-325 MUM.
      Additionally, over a 90 day period, the repeatability for 200 MUM samples of
      lactate remained below 3.4% (RSD). Direct electron transfer was observed between
      the LOx redox-active center and the N-CNTs with the electroactive surface
      coverage determined to be 0.27 nmol cm(-2).

PMID- 21942441
TI  - The evaluation of basic fibroblast growth factor and fibroblastic growth factor
      receptor 1 levels in saliva and serum of patients with salivary gland tumor.
AB  - Basic fibroblast growth factor (FGF2) is a well-known endothelial mitogen that
      regulates endothelial cell proliferation, migration, differentiation, and
      survival. In the present study, we investigated the levels of FGF2 and
      fibroblastic growth factor receptor 1 (FGFR1) in saliva and serum of patients
      with salivary gland tumors. Saliva and serum samples were collected from 43
      patients with salivary gland tumors and 40 healthy volunteers. The FGF2 and FGFR1
      concentrations in saliva and serum samples were measured by enzyme-linked
      immunosorbent assay. We found that the levels of FGF2 and FGFR1 in saliva and
      serum from patients with salivary gland tumors were significantly higher than
      those from healthy control subjects. These results suggest that salivary FGF2 and
      FGFR1 can be used as potential biomarkers in the diagnosis of salivary gland
      tumors.

PMID- 21942443
TI  - Interaction of MTHFR 1298C with ACE D allele augments the risk of diabetic
      nephropathy in Western Iran.
AB  - The aim of the current study was to examine the influence of interaction between
      polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C
      with angiotensin converting enzyme insertion/deletion (ACE I/D) polymorphism on
      the risk of diabetic nephropathy (DN). In a case control study using polymerase
      chain reaction (PCR)- and PCR-restriction fragment length polymorphism (RFLP),
      the presence of three polymorphisms in 140 patients with type 2 diabetes mellitus
      (T2DM) with nephropathy including patients with micro- and macro-albuminuria and
      72 patients with normoalbuminuria from Western Iran were investigated. In the
      presence of both MTHFR 677 T and ACE D alleles, there was a trend toward
      increased risk of DN 2.68-fold (p=0.054). The possession of both MTHFR 677 T and
      ACE D alleles increased the risk of macro-albuminuria four times (p=0.035). The
      concomitant presence of both MTHFR 1298 C and ACE D alleles increased the risk of
      macro-albuminuria 7.8-fold (p=0.012). In addition, the risk of progression from
      micro- to macro-albuminuria in the presence of both alleles tended to be
      increased (4.1-fold, p=0.09). Our study for the first time demonstrated a
      synergistic effect between ACE I/D with either MTHFR C677T or A1298C polymorphism
      on the increased risk of DN among patients with T2DM. We found that MTHFR 1298 C
      strongly interacts with the ACE D allele and augments the risk of DN in our
      population.

PMID- 21942442
TI  - Incomplete chromatin condensation in enlarged rat myelocytic leukemia cells.
AB  - The distinguishable morphologic features of nuclei of acute myelogenous leukemia
      cells with enlarged size and finely distributed nuclear chromatin indicate
      incomplete chromosome condensation that can be related to elevated gene
      expression. To confirm this, interphase chromosome structures were studied in
      exponentially growing rat myelomonocytic leukemia 1 cells isolated at the
      University of Debrecen (My1/De cells). This cell line was established from
      primary rat leukemia chemically induced by 7,12-dimethylbenz[a]anthracene
      treatment. The enlarged nuclei of My1/De cells allowed improved fluorescent
      visualization of chromosomal structures. Increased resolution revealed major
      interphase intermediates consisting of (1) veil-like chromatin, (2) chromatin
      ribbon, (3) chromatin funnel, (4) chromatin bodies, (5) elongated prechromosomes,
      (6) seal-ring, spiral shaped, and circular chromosomal subunits, (7) elongated,
      bent, u- and v-shaped prechromosomes, and (8) metaphase chromosomes. Results
      confirmed the existence of the chromatin funnel, the first visible interphase
      chromosome generated by the supercoiling of the chromatin ribbon. Other
      intermediates not seen previously included the spiral subunits that are involved
      in the chromonemic folding of metaphase chromosomes. The existence of spiral
      subunits favors the helical coil model of chromosome condensation. Incomplete
      chromatin condensation in leukemia cells throughout the cell cycle is an
      indication of euchromatization contributing to enhanced gene expression and is
      regarded as a leukemic factor.

PMID- 21942444
TI  - Direct grafting of long-lived luminescent indicator dyes to GaN light-emitting
      diodes for chemical microsensor development.
AB  - Two new methods for covalent functionalization of GaN based on plasma activation
      of its surface are presented. Both of them allow attachment of sulfonated
      luminescent ruthenium(II) indicator dyes to the p- and n-type semiconductor as
      well as to the surface of nonencapsulated chips of GaN light-emitting diodes
      (blue LEDs). X-ray photoelectron spectroscopy analysis of the functionalized
      semiconductor confirms the formation of covalent bonds between the GaN surface
      and the dye. Confocal fluorescence microscopy with single-photon-timing (SPT)
      detection has been used for characterization of the functionalized surfaces and
      LED chips. While the ruthenium complex attached to p-GaN under an oxygen-free
      atmosphere gives significantly long mean emission lifetimes for the indicator dye
      (ca. 2000 ns), the n-GaN-functionalized surfaces display surprisingly low values
      (600 ns), suggesting the occurrence of a quenching process. A photoinduced
      electron injection from the dye to the semiconductor conduction band, followed by
      a fast back electron transfer, is proposed to be responsible for the excited
      ruthenium dye deactivation. This process invalidates the use of the n-GaN/dye
      system for sensing applications. However, for p-GaN/dye materials, the
      luminescence decay accelerates in the presence of O(2). The moderate sensitivity
      is attributed to the fact that only a monolayer of indicator dye is anchored to
      the semiconductor surface but serves as a demonstrator device. Moreover, the
      luminescence decays of the functionalized LED chip measured with excitation of
      either an external (laser) source or the underlying LED emission (from p
      GaN/InGaN quantum wells) yield the same mean luminescence lifetime. These results
      pave the way for using advanced LEDs to develop integrateable optochemical
      microsensors for gas analysis.

PMID- 21942446
TI  - Solubility of aliphatic hydrocarbons in piperidinium ionic liquids: measurements
      and modeling in terms of perturbed-chain statistical associating fluid theory and
      nonrandom hydrogen-bonding theory.
AB  - Ionic liquids (ILs) reveal many unique properties which make them very
      interesting for applications in modern "green" technologies. For that reason,
      detailed knowledge about correlations between the ions' structure, their
      combinations, and the bulk properties is of great importance. That knowledge can
      be accessed by reliable measurements and modeling of systems with ILs in terms of
      various theoretical approaches. In this paper we report new experimental results
      on liquid-liquid equilibrium (LLE) measurements of 10 binary systems composed of
      piperidinium ILs [namely, 1-propyl-1-methylpiperidinium
      bis(trifluoromethylsulfonyl)imide and 1-butyl-1-methylpiperidinium
      bis(trifluoromethylsulfonyl)imide] and aliphatic hydrocarbons (n-hexane, n
      heptane, n-octane, cyclohexane, and cycloheptane). Moreover, new results on
      liquid density of pure 1-butyl-1-methylpiperidinium
      bis(trifluoromethylsulfonyl)imide are presented. Upper critical solution
      temperature type of phase behavior for all studied systems was observed. Decrease
      of solubility of n-alkane with an increase of its alkyl chain length and increase
      of solubility when changing linear into cyclic structure of hydrocarbon were
      detected. LLE modeling of investigated systems was performed in terms of two
      modern theories, namely, perturbed-chain statistical associating fluid theory (PC
      SAFT) and nonrandom hydrogen-bonding theory (NRHB). Pure fluid parameters of the
      models were obtained from fitting of experimental liquid density and solubility
      parameter data at ambient pressure and tested against high pressure densities.
      Then literature values of activity coefficients of n-alkanes and cycloalkanes at
      infinitely diluted mixtures with ILs were used to optimize binary interaction
      parameters of the models. Finally, the LLE phase diagrams were calculated with
      average absolute relative deviations of 4.1% and 3.4% of the IL mole fraction for
      PC-SAFT and NRHB, respectively. The PC-SAFT and NRHB models were both able to
      capture phase behavior in a qualitative manner. Both models predict the order in
      which solubility of hydrocarbon in the IL increases, including the effects of
      chain length of n-alkane as well as chain length of alkyl substituent in
      piperidinium cation. Moreover, predicted solubility of cycloalkanes is also
      higher than that of respective n-alkanes. Our results suggest that the presented
      approach of PC-SAFT and NRHB modeling can be successfully applied to cross
      associating systems as well. In summary, we have shown that relatively good
      results can be obtained for such complex systems by using quite simple molecular
      models and combining rules. To the best of our knowledge, this is the very first
      paper in which such equation-of-state modeling has been adopted for systems with
      ILs.

PMID- 21942447
TI  - Resveratrol modulates MED28 (Magicin/EG-1) expression and inhibits epidermal
      growth factor (EGF)-induced migration in MDA-MB-231 human breast cancer cells.
AB  - Resveratrol and pterostilbene exhibit diverse biological activities. MED28, a
      subunit of the mammalian Mediator complex for transcription, was also identified
      as magicin, an actin cytoskeleton Grb2-associated protein, and as endothelial
      derived gene (EG-1). Several tumors exhibit aberrant MED28 expression, whereas
      the underlying mechanism is unclear. Triple-negative breast cancers, often
      expressing epidermal growth factor (EGF) receptor (EGFR), are associated with
      metastasis and poor survival. The objective of this study is to compare the
      effect of resveratrol and pterostilbene and to investigate the role of MED28 in
      EGFR-overexpressing MDA-MB-231 breast cancer cells. Pretreatment of resveratrol,
      but not pterostlbene, suppressed EGF-mediated migration and expression of MED28
      and matrix metalloproteinase (MMP)-9 in MDA-MB-231 cells. Moreover,
      overexpression of MED28 increased migration, and the addition of EGF further
      enhanced migration. Our data indicate that resveratrol modulates the effect of
      MED28 on cellular migration, presumably through the EGFR/phosphatidylinositol 3
      kinase (PI3K) signaling pathway, in breast cancer cells.

PMID- 21942448
TI  - Artemisia dracunculus L. (tarragon): a critical review of its traditional use,
      chemical composition, pharmacology, and safety.
AB  - Artemisia dracunculus  L. (tarragon) has a long history of use as a spice and
      remedy. Two well-described "cultivars" (Russian and French) are used widely and
      differ in ploidy level, morphology, and chemistry. Key biologically active
      secondary metabolites are essential oils (0.15-3.1%), coumarins (>1%),
      flavonoids, and phenolcarbonic acids. In vivo studies mainly in rodents,
      particularly from Russian sources, highlight potential anti-inflammatory,
      hepatoprotective, and antihyperglycemic effects. Despite concerns about the toxic
      effects of two of its main constituents, estragole (up to 82%) and methyleugenol
      (up to 39%), no acute toxicity or mutagenic activity has been reported at doses
      relevant for human consumption. Water extracts of A. dracunculus contain very low
      amounts of estragole and methyleugenol and, therefore, are considered to pose a
      very limited risk. Overall, a stronger focus on clinical studies and precise
      taxonomic and phytochemical definition of the source material will be essential
      for future research efforts.

PMID- 21942449
TI  - Mesoporous manganese oxide nanowires for high-capacity, high-rate, hybrid
      electrical energy storage.
AB  - Arrays of mesoporous manganese dioxide, mp-MnO(2), nanowires were
      electrodeposited on glass and silicon surfaces using the lithographically
      patterned nanowire electrodeposition (LPNE) method. The electrodeposition
      procedure involved the application, in a Mn(ClO(4))(2)-containing aqueous
      electrolyte, of a sequence of 0.60 V (vs MSE) voltage pulses delineated by 25 s
      rest intervals. This "multipulse" deposition program produced mp-MnO(2) nanowires
      with a total porosity of 43-56%. Transmission electron microscopy revealed the
      presence within these nanowires of a network of 3-5 nm diameter fibrils that were
      X-ray and electron amorphous, consistent with the measured porosity values. mp
      MnO(2) nanowires were rectangular in cross-section with adjustable height,
      ranging from 21 to 63 nm, and adjustable width ranging from 200 to 600 nm. Arrays
      of 20 nm * 400 nm mp-MnO(2) nanowires were characterized by a specific
      capacitance, C(sp), of 923 +/- 24 F/g at 5 mV/s and 484 +/- 15 F/g at 100 mV/s.
      These C(sp) values reflected true hybrid electrical energy storage with
      significant contributions from double-layer capacitance and noninsertion
      pseudocapacitance (38% for 20 nm * 400 nm nanowires at 5 mV/s) coupled with a
      Faradaic insertion capacity (62%). These two contributions to the total C(sp)
      were deconvoluted as a function of the potential scan rate.

PMID- 21942450
TI  - Ion transport and molecular organization are coupled in polyelectrolyte-modified
      nanopores.
AB  - Chemically modified nanopores show a strong and nontrivial coupling between ion
      current and the structure of the immobilized species. In this work we study
      theoretically the conductance and structure in polymer modified nanopores and
      explicitly address the problem of the coupling between ion transport and
      molecular organization. Our approach is based on a nonequilibrium molecular
      theory that couples ion conductivity with the conformational degrees of freedom
      of the polymer and the electrostatic and nonelectrostatic interactions among
      polyelectrolyte chains, ions, and solvent. We apply the theory to study a
      cylindrical nanopore between two reservoirs as a function of pore diameter and
      length, the length of the polyelectrolyte chains, their grafting density, and
      whether they are present or not on the outer reservoir walls. In the very low
      applied potential regime, where the distribution of polyelectrolyte and ions is
      similar to that in equilibrium, we present a simple analytical model based on the
      combination of the different resistances in the system that describes the
      conductance in excellent agreement with the calculations of the full
      nonequilibrium molecular theory. On the other hand, for a large applied potential
      bias, the theory predicts a dramatic reorganization of the polyelectrolyte chains
      and the ions. This reorganization results from the global optimization of the
      different interactions in the system under nonequilibrium conditions. For
      nanopores modified with long chains, this reorganization leads to two interesting
      physical phenomena: (i) control of polyelectrolyte morphology by the direction
      and magnitude of ion-fluxes and (ii) an unexpected decrease in system resistance
      with the applied potential bias for long chains due to the coupling between
      polyelectrolyte segment distribution and ion currents.

PMID- 21942451
TI  - Burkholderia phytofirmans PsJN primes Vitis vinifera L. and confers a better
      tolerance to low nonfreezing temperatures.
AB  - Several endophytic bacteria reportedly induce resistance to biotic stress and
      abiotic stress tolerance in several plant species. Burkholderia phytofirmans PsJN
      is a plant-growth-promoting rhizobacterium (PGPR) that is able to colonize
      grapevine tissues and induce resistance to gray mold. Further, PsJN induces
      physiological changes that increase grapevine tolerance to low nonfreezing
      temperatures. To better understand how bacteria induced the observed phenomena,
      stress-related gene expression and metabolite accumulation were monitored in 6
      week-old Chardonnay grapevine plantlets after exposure to low nonfreezing
      temperatures. Under normal conditions (26 degrees C), plantlet bacterization had
      no significant effect on the monitored parameters. By contrast, at 4 degrees C,
      both stress-related gene transcripts and metabolite levels increased earlier and
      faster, and reached higher levels in PsJN-bacterized plantlets than in
      nonbacterized counterparts, in accordance with priming phenomena. The recorded
      changes may be correlated with the tolerance to cold stress conferred by the
      presence of PsJN. This is the first time that PGPR-induced priming has been shown
      to protect plants against low-temperature stress. Moreover, 1 week after cold
      exposure, levels of stress-related metabolites had declined more in PsJN
      bacterized plants, suggesting that the endophyte is involved in the cold
      acclimation process via the scavenging system.

PMID- 21942452
TI  - A highly conserved effector in Fusarium oxysporum is required for full virulence
      on Arabidopsis.
AB  - Secreted-in-xylem (SIX) proteins of the vascular wilt pathogen Fusarium oxysporum
      f. sp. lycopersici are secreted during infection of tomato and function in
      virulence or avirulence. F. oxysporum formae speciales have specific host ranges
      but the roles of SIX proteins in diverse hosts are unknown. We identified
      homologs of F. oxysporum f. sp. lycopersici SIX1, SIX4, SIX8, and SIX9 in the
      genome of Arabidopsis infecting isolate Fo5176. A SIX4 homolog (termed Fo5176
      SIX4) differed from that of F. oxysporum f. sp. lycopersici (Fol-SIX4) by only
      two amino acids, and its expression was induced during infection of Arabidopsis.
      Transgenic Arabidopsis plants constitutively expressing Fo5176-SIX4 had increased
      disease symptoms with Fo5176. Conversely, Fo5176-SIX4 gene knock-out mutants
      (Deltasix4) had significantly reduced virulence on Arabidopsis, and this was
      associated with reduced fungal biomass and host jasmonate-mediated gene
      expression, the latter known to be essential for host symptom development. Full
      virulence was restored by complementation of Deltasix4 mutants with either Fo5176
      SIX4 or Fol-SIX4. Thus, Fo5176-SIX4 contributes quantitatively to virulence on
      Arabidopsis whereas, in tomato, Fol-SIX4 acts in host specificity as both an
      avirulence protein and a suppressor of other race-specific resistances. The
      strong sequence conservation for SIX4 in F. oxysporum f. sp. lycopersici and
      Fo5176 suggests a recent common origin.

PMID- 21942456
TI  - Fabrication and photoluminescent properties of ZnO/mesoporous silica composites
      templated by a chelating surfactant.
AB  - A novel anionic surfactant-templated synthesis of ZnO/mesoporous silica
      nanocomposites has been carried out by using N-hexadecylethylenediamine
      triacetate (HED3A), a triprotic surfactant, as the structure-directing agent. The
      chelating template can capture zinc ions in solution and then direct the
      mesophase formation, enabling an amount of zinc oxide to be embedded in the
      porous silica matrix during calcination. With variation of the molar ratio of
      Zn(2+) to HED3A in the template, a series of composites with different doping
      amounts were obtained after the removal of organic components. The variation of
      the zinc ion concentration in the initial template solution induces an evolution
      of the silica mesophase, presumably due to the change in electronegativity of the
      HED3A headgroup caused by the chelating effect. Spectroscopic studies show a
      strong host-guest interaction between the silica pore walls and ultrafine ZnO
      nanoparticles. The photoluminescence properties of the resulting composites
      exhibit a size-dependent light emission and quantum-confinement effect of ZnO,
      accompanied by an infrequent violet emission originating from the ZnO-SiO(2)
      interface.

PMID- 21942457
TI  - Built-in electric field minimization in (In, Ga)N nanoheterostructures.
AB  - (In, Ga)N nanostructures show great promise as the basis for next generation LED
      lighting technology, for they offer the possibility of directly converting
      electrical energy into light of any visible wavelength without the use of down
      converting phosphors. In this paper, three-dimensional computation of the spatial
      distribution of the mechanical and electrical equilibrium in nanoheterostructures
      of arbitrary topologies is used to elucidate the complex interactions between
      geometry, epitaxial strain, remnant polarization, and piezoelectric and
      dielectric contributions to the self-induced internal electric fields. For a
      specific geometry-nanorods with pyramidal caps-we demonstrate that by tuning the
      quantum well to cladding layer thickness ratio, h(w)/h(c), a minimal built-in
      electric field can be experimentally realized and canceled, in the limit of
      h(w)/h(c) = 1.28, for large h(c) values.

PMID- 21942458
TI  - A new species of Spauligodon (Nematoda: Oxyurida: Pharyngodonidae) in geckos from
      Sao Nicolau Island (Cape Verde) and its phylogenetic assessment.
AB  - A new nematode species, Spauligodon nicolauensis n. sp., is described from geckos
      Tarentola bocagei and Tarentola nicolauensis on the island of Sao Nicolau, Cape
      Verde. The new nematode was found in the pellets obtained directly from the
      geckos in a non-invasive fashion, and its identity was assessed both at
      morphologic and genetic levels. The new species has morphological similarities
      with Spauligodon tarentolae Spaul, 1926, also parasitizing geckos from the Canary
      Islands. However, the male cloacal region in the new species is distinct,
      presenting a different shape of the caudal papillae. The overall resemblance
      probably resulted from colonization via descent from an ancestor of S. tarentolae
      carried by the ancestor of Cape Verde Tarentola. The analysis of nuclear DNA
      sequences confirms that the new species is phylogenetically distinct from all
      other Spauligodon species already analyzed, forming a group clearly separated
      from species parasitizing lacertid lizards. The COI genetic distance suggests
      that the S. nicolauensis n. sp. found in the 2 species of geckos in Sao Nicolau
      Island may have resulted from a host-switching event, when they came into contact
      after the unification of the island.

PMID- 21942461
TI  - Incremental binding energies of gold(I) and silver(I) thiolate clusters.
AB  - Density functional theory is used to find incremental fragmentation energy,
      overall dissociation energy, and average monomer fragmentation energy of cyclic
      gold(I) thiolate clusters and anionic chain structures of gold(I) and silver(I)
      thiolate clusters as a measure of the relative stability of these systems. Two
      different functionals, BP86 and PBE, and two different basis sets, TZP and QZ4P,
      are employed. Anionic chains are examined with various residue groups including
      hydrogen, methyl, and phenyl. Hydrogen and methyl are shown to have approximately
      the same binding energy, which is higher than phenyl. Gold-thiolate clusters are
      bound more strongly than corresponding silver clusters. Lastly, binding energies
      are also calculated for pure Au(25)(SR)(18)(-), Ag(25)(SR)(18)(-), and mixed
      Au(13)(Ag(2)(SH)(3))(6)(-) and Ag(13)(Au(2)(SH)(3))(6)(-) nanoparticles.

PMID- 21942462
TI  - Economic impact of tobramycin in patients with cystic fibrosis in a managed care
      population.
AB  - OBJECTIVE: Guidelines recommend chronic use of tobramycin solution for inhalation
      (TSI) for cystic fibrosis (CF) patients with moderate-to-severe lung disease and
      persistent airway Pseudomonas aeruginosa. This study evaluated the economic
      impact of TSI in managed care CF patients. METHODS: Patients (0-64 years) with
      >=2 CF medical claims between 01/01/04-03/31/09 were identified. For TSI users,
      the index date was the first TSI claim in the period; for non-users, a pseudo
      index date was determined and randomly assigned by simulating the distribution of
      index dates of TSI users. Maximum sample size was obtained for patients with >=3
      months pre- and >=12 months post-index eligibility. Users were categorized by
      number of TSI prescriptions filled during 12-month post-index period as low (1
      fill), medium (2-3 fills) and high adherence (>=4 fills). Differences in per
      member per month (PMPM) costs pre-index to post-index were analyzed using paired
      t-tests. RESULTS: A total of 388 TSI users (mean age 19 years, 48% female) and
      444 non-users (mean age 30 years, 54% female) met study criteria. In users, total
      and CF-related PMPM costs decreased $959 (17%) and $113 (3%), respectively, after
      starting TSI. Among TSI users, CF-related inpatient PMPM costs decreased by $1171
      (49%; p=0.01), while CF-related prescription PMPM costs increased by $992
      (p<0.01). CF-related inpatient PMPM costs decreased by $381 (38%; p=0.16) for low
      and $1425 (50%; p=0.21) for medium users and decreased by $1829 (51%; p=0.02) for
      high users. LIMITATIONS: Limitations include use of administrative claims data,
      small sample size due to disease rarity, random assignment of pseudo-index date
      to non-users and differences in baseline characteristics between TSI users and
      non-users. CONCLUSION: All-cause and CF-related PMPM medical costs significantly
      decreased after TSI initiation. Among TSI users, total healthcare costs
      decreased, although not significantly, due to PMPM increases in prescription
      costs. A trend towards greater decrease in inpatient PMPM costs was observed with
      increasing TSI adherence.

PMID- 21942463
TI  - Comparative effectiveness of budesonide/formoterol and fluticasone/salmeterol for
      COPD management.
AB  - OBJECTIVE: To compare the effectiveness of budesonide/formoterol fumarate
      dihydrate (BFC) and fluticasone propionate/salmeterol (FSC), two combination
      inhaled corticosteroid/long-acting beta-agonist (ICS/LABA) products approved for
      the treatment of chronic obstructive pulmonary disease (COPD) in the US with
      respect to cost, therapy adherence, and related healthcare utilization. The
      effectiveness of these two treatments has not previously been compared in a US
      COPD population. METHODS: A retrospective cohort study assessed COPD-related
      outcomes using administrative claims data among ICS/LABA-naive patients. Patients
      initiating BFC were propensity matched to FSC patients. Cost and effectiveness
      were measured as total healthcare expenditures, exacerbation events
      (hospitalizations, emergency department visits, or outpatient visits associated
      with oral corticosteroid or antibiotic prescription fills), and treatment
      medication adherence. Differences in COPD symptom control were assessed via proxy
      measure through claims for rescue medications and outpatient encounters. RESULTS:
      Of the 6770 patients (3385 BFC and 3385 FSC), fewer BFC patients had claims for
      short-acting beta agonists (SABA) (34.7% vs 39.5%; p<0.001) and ipratropium (7.8%
      vs 9.8%, p<0.005) than FSC patients, but no substantial differences were seen in
      other clinical outcomes including tiotropium or nebulized SABA claims, COPD
      related outpatient visits, or exacerbation events. There were no significant
      differences in total COPD-related medical costs in the 6-month period after
      initiation of combination therapy. LIMITATIONS: This was a retrospective
      observational study using claims data and accuracy of COPD diagnoses could not be
      verified, nor was information available on severity of disease. The results and
      conclusions of this study are limited to the population observed and the
      operational definitions of the study variables. CONCLUSIONS: For most outcomes of
      interest, BFC and FSC showed comparable real-world effectiveness.

PMID- 21942464
TI  - Behavior of neutral phosphido derivatives of platinum and palladium toward silver
      centers.
AB  - The reaction of the neutral binuclear complexes [(R(F))(2)Pt(MU
      PPh(2))(2)M(phen)] (phen = 1,10-phenanthroline, R(F) = C(6)F(5); M = Pt, 1; M =
      Pd, 2) with AgClO(4) or [Ag(OClO(3))(PPh(3))] affords the trinuclear complexes
      [AgPt(2)(MU-PPh(2))(2)(R(F))(2)(phen)(OClO(3))] (7a) or [AgPtM(MU
      PPh(2))(2)(R(F))(2)(phen)(PPh(3))][ClO(4)] (M = Pt, 8; M = Pd, 9), which display
      an "open-book" type structure and two (7a) or one (8, 9) Pt-Ag bonds. The neutral
      diphosphine complexes [(R(F))(2)Pt(MU-PPh(2))(2)M(P-P)] (P-P = 1,2
      bis(diphenylphosphino)methane, dppm, M = Pt, 3; M = Pd, 4; P-P = 1,2
      bis(diphenylphosphino)ethane, dppe, M = Pt, 5; M = Pd, 6) react with AgClO(4) or
      [Ag(OClO(3))(PPh(3))], and the nature of the resulting complexes is dependent on
      both M and the diphosphine. The dppm Pt-Pt complex 3 reacts with
      [Ag(OClO(3))(PPh(3))], affording a silver adduct 10 in which the Ag atom
      interacts with the Pt atoms, while the dppm Pt-Pd complex 4 reacts with
      [Ag(OClO(3))(PPh(3))], forming a 1:1 mixture of [AgPdPt(MU
      PPh(2))(2)(R(F))(2)(OClO(3))(dppm)] (11), in which the silver atom is connected
      to the Pt-Pd moiety through Pd-(MU-PPh(2))-Ag and Ag-P(k(1)-dppm) interactions,
      and [AgPdPt(MU-PPh(2))(2)(R(F))(2)(OClO(3))(PPh(3))(2)][ClO(4)] (12). The
      reaction of complex 4 with AgClO(4) gives the trinuclear derivative 11 as the
      only product. Complex 11 shows a dynamic process in solution in which the silver
      atom interacts alternatively with both Pd-MUPPh(2) bonds. When P-P is dppe, both
      complexes 5 and 6 react with AgClO(4) or [Ag(OClO(3))(PPh(3))], forming the
      saturated complexes [(PPh(2)C(6)F(5))(R(F))Pt(MU-PPh(2))(MU-OH)M(dppe)][ClO(4)]
      (M = Pt, 13; Pd, 14), which are the result of an oxidation followed by a
      PPh(2)/C(6)F(5) reductive coupling. Finally, the oxidation of trinuclear
      derivatives [(R(F))(2)Pt(II)(MU-PPh(2))(2)Pt(II)(MU-PPh(2))(2)Pt(II)L(2)] (L(2) =
      phen, 15; L = PPh(3), 16) by AgClO(4) results in the formation of the unsaturated
      46 VEC complexes [(R(F))(2)Pt(III)(MU-PPh(2))(2)Pt(III)(MU
      PPh(2))(2)Pt(II)L(2)][ClO(4)](2) (17 and 18, respectively) which display Pt(III)
      Pt(III) bonds.

PMID- 21942465
TI  - Comparative evaluation of efficacy and safety of etodolac and diclofenac sodium
      injection in patients with postoperative orthopedic pain.
AB  - OBJECTIVE: The objective of this study was to compare the analgesic efficacy of
      etodolac injection and diclofenac injection in patients with postoperative
      orthopedic pain. METHODS: This was multicentric, randomized, assessor-blind and
      parallel-group study. A group of 158 patients with moderate to severe pain
      following orthopedic surgery were randomly assigned to receive either etodolac
      400 mg twice a day (n = 78) or diclofenac 75 mg thrice a day (n = 80). MAIN
      OUTCOME MEASURES: The primary efficacy outcome measures were pain intensity
      difference, sum of pain intensity differences and pain relief whereas secondary
      efficacy variables included maximum fall in pain intensity, number of doses of
      study medication consumed, number of patients who required rescue medication and
      overall response to therapy. RESULTS: Mean pain intensity differences assessed on
      10 cm VAS were significantly better for etodolac arm compared to diclofenac arm
      at 4, 8, 20 and 24 hours (p < 0.05). Sum of pain intensity differences over the
      first 8 hours (-21.31 +/- 6.26 for etodolac vs. -19.13 +/- 6.98 for diclofenac; p
      = 0.041) and over the 24 hours (-39.83 +/- 10.70 for etodolac vs. -35.25 +/-
      12.00 for diclofenac; p = 0.012) for the etodolac group was significantly
      superior than diclofenac group. Assessment of pain relief showed that etodolac
      injection was significantly more effective than diclofenac injection (p < 0.0001)
      over the 24 hour assessment period. Maximum fall in pain intensity score, number
      of doses of study medication consumed and patients' and investigators' overall
      response to the drug at the end of treatment period were also significantly
      superior in the etodolac arm as compared to the diclofenac arm (p < 0.05).
      However, the number of patients who were rescued was comparable in both the
      treatment arms. A change in emotional functioning of the patients was not
      captured in this study. Both the study medications were well tolerated with no
      incidence of SAE throughout the study. CONCLUSION: Etodolac can be considered as
      an effective alternative to traditional NSAIDS in the treatment of post operative
      pain.

PMID- 21942466
TI  - Therapeutic potential of apixaban in the prevention of venous thromboembolism in
      patients undergoing total knee replacement surgery.
AB  - BACKGROUND: Apixaban is a novel oral factor Xa inhibitor that recently completed
      evaluation in clinical trials for its use in the prevention of venous
      thromboembolism (VTE) in patients undergoing hip or knee replacement surgery. Its
      manufacturers are currently seeking approval for these indications in the
      European Union and a rolling submission is in process in the United States.
      SCOPE: This article reviews published data on the efficacy and safety profile of
      apixaban in patients undergoing total knee arthroplasty (TKA). For this review,
      the authors searched PubMed for English language clinical trial articles
      involving the use of apixaban in human subjects published through July 11, 2011.
      The key words 'apixaban' and 'total knee arthroplasty/replacement' were used. The
      review focused on clinical trials, but other articles were reviewed for relevant
      information. FINDINGS: One dose-finding phase II trial demonstrated apixaban's
      efficacy and a dose of 2.5 mg twice daily was established for future
      investigation. Two phase III clinical trials have been completed with apixaban in
      TKA patients (ADVANCE-1 and ADVANCE-2). In ADVANCE-1, apixaban did not meet the
      pre-specified non-inferiority criteria, while in ADVANCE-2, apixaban met the non
      inferiority criteria when compared to enoxaparin, and had a similar safety
      profile. CONCLUSION: Apixaban is a promising new agent awaiting regulatory
      approval for its use in thromboprophylaxis after TKA.

PMID- 21942467
TI  - Barriers to effective insulin treatment: the persistence of poor glycemic control
      in type 2 diabetes.
AB  - BACKGROUND: Contrary to longstanding recommendations on type 2 diabetes (T2D)
      management, the de facto standard of care in Canada includes lag times of many
      years prior to introducing effective glycemic control. Even patients transitioned
      to insulin may continue to experience poor glycemic control, with attendant
      diabetic complications, suggesting poor adherence or inadequate dose titration.
      OBJECTIVE: To identify barriers to timely and effective use of insulin in T2D.
      METHODS: PubMed searches were conducted to find research articles on insulin
      initiation, adherence and intensification. Also, because recent data on the
      consequences of intensive glycemic control may be taken as justification for
      relaxing glycemic targets, a secondary search on this literature was conducted,
      including the UKPDS and ACCORD trials, plus post hoc and meta-analyses of these
      data. No formal evaluation of level of evidence was conducted while researching
      this narrative literature review. FINDINGS: Timely, effective glycemic control
      remains an important clinical goal but is complicated by patient, physician and
      treatment factors. Patient barriers to accepting insulin initiation include fear
      of hypoglycemia, injections and weight gain, and reluctance to accommodate the
      inflexible timing of scheduled insulin doses. Adherence issues, including dose
      omission, are common and are associated with some of the same factors. Fear of
      hypoglycemia also underlies many physicians' reluctance to prescribe insulin.
      Caregivers' failure to provide training or answer questions about insulin's risks
      and benefits was also associated with low patient adherence. Poor communication
      may also be at fault when patients on insulin fail to titrate or intensify their
      treatment adequately. Conversely, glycemic control can be significantly improved
      by facilitating ongoing communication between patients and caregivers.
      DISCUSSION: Although innovations in injectable therapy for T2D may help address
      the current pattern of poor glycemic control, improved communication between
      patients and caregivers is also a powerful approach and can be implemented with
      existing therapies.

PMID- 21942468
TI  - Mechanistic and physiological implications of the interplay among iron-sulfur
      clusters in [FeFe]-hydrogenases. A QM/MM perspective.
AB  - Key stereoelectronic properties of Desulfovibrio desulfuricans [FeFe]-hydrogenase
      (DdH) were investigated by quantum mechanical description of its complete
      inorganic core, which includes a Fe(6)S(6) active site (the H-cluster), as well
      as two ancillary Fe(4)S(4) assemblies (the F and F' clusters). The partially
      oxidized, active-ready form of DdH is able to efficiently bind dihydrogen, thus
      starting H(2) oxidation catalysis. The calculations allow us to unambiguously
      assign a mixed Fe(II)Fe(I) state to the catalytic core of the active-ready enzyme
      and show that H(2) uptake exerts subtle, yet crucial influences on the redox
      properties of DdH. In fact, H(2) binding can promote electron transfer from the H
      cluster to the solvent-exposed F'-cluster, thanks to a 50% decrease of the energy
      gap between the HOMO (that is localized on the H-cluster) and the LUMO (which is
      centered on the F'-cluster). Our results also indicate that the binding of the
      redox partners of DdH in proximity of its F'-cluster can trigger one-electron
      oxidation of the H(2)-bound enzyme, a process that is expected to have an
      important role in H(2) activation. Our findings are analyzed not only from a
      mechanistic perspective, but also in consideration of the physiological role of
      DdH. In fact, this enzyme is known to be able to catalyze both the oxidation and
      the evolution of H(2), depending on the cellular metabolic requirements. Hints
      for the design of targeted mutations that could lead to the enhancement of the
      oxidizing properties of DdH are proposed and discussed.

PMID- 21942469
TI  - New generation photocatalysts: how tungsten influences the nanostructure and
      photocatalytic activity of TiO2 in the UV and visible regions.
AB  - Tungsten-doped anatase was prepared by a thermal hydrolysis of aqueous solutions
      of peroxo complexes of titanium and tungsten. The synthesized samples included X
      ray diffraction, high-resolution transmission electron microscopy, selected area
      electron diffraction, Raman spectroscopy, specific surface area, and porosity
      determination. W doping resulted in a decrease of the unit-cell volume of anatase
      at lower W contents and an increase at higher W contents. The position of the
      most intense Raman band of the E(g) mode (near 147 cm(-1)) also has a local
      minimum at medium-doped titania (1.1-3.6% W in titania). W doping increases the
      temperature of anatase-to-rutile transformation by about 100  degrees C compared
      with nondoped anatase. The photocatalytic activity of doped titania samples was
      determined by decomposition of Orange II dye during irradiation at 365 and 400
      nm. Specimens with moderate W doping (1.0-3.3% W) perform best: they enhance the
      corresponding reaction rates 10 times at 365 nm and 5 times at 400 nm,
      respectively, compared with pure titania obtained under the same set of synthesis
      conditions.

PMID- 21942470
TI  - Conformational flexibility of C8-phenoxylguanine adducts in deoxydinucleoside
      monophosphates.
AB  - M06-2X/6-31G(d,p) is used to calculate the structure of all natural
      deoxydinucleoside monophosphates with G in the 5' or 3' position, the anti or syn
      conformation, and each natural (A, C, G, T) base in the corresponding flanking
      position. When the ortho or para C8-phenoxyl-2'-deoxyguanosine (C8-phenoxyl-dG)
      adduct replaces G in each model, there is little change in the relative base-base
      orientation or backbone conformation. However, the orientation of the C8-phenoxyl
      group can be characterized according to the position (5' versus 3'), conformation
      (anti versus syn), and isomer (ortho versus para) of damage. Although the degree
      of coplanarity between the phenoxyl ring and G base in the ortho adduct is highly
      affected by the sequence since the hydroxyl group can interact with neighboring
      bases, the para adduct generally does not exhibit discrete interactions with
      flanking bases. For both adducts, steric clashes between the phenoxyl group and
      the backbone or flanking base destabilize the anti conformation preferred by the
      natural nucleotide and thereby result in a clear preference for the syn
      conformation regardless of the sequence or position. This contrasts the
      conclusions drawn from smaller (nucleoside, nucleotide) models previously used in
      the literature, which stresses the importance of using models that address the
      steric constraints present due to the surrounding environment. Since replication
      errors for other C8-dG bulky adducts have been linked to a preference for the syn
      conformation, our findings provide insight into the possible mutagenicity of
      phenolic adducts.

PMID- 21942471
TI  - A novel lignan glycoside with antioxidant activity from Tinospora sagittata var.
      yunnanensis.
AB  - A novel lignan glysocide, namely sagitiside A (1), together with two known ones,
      (+)-lyoniresinol-2alpha-O-beta-D-glucopyranoside (2) and (+)-5'
      methoxyisolariciresinol 3alpha-O-beta-D-glucopyranoside (3), was isolated from
      the 95% ethanol extract of dry roots of Tinospora sagittata var. yunnanensis. The
      structure of the new compound (1) was determined based on MS, 1D and 2D NMR
      spectral data. Compounds 1-3 showed antioxidant activity with EC(50) values 55,
      75 and 80 uM by 1,1-diphenyl-2-picryhydrazyl (DPPH) radical-scavenging assay.

PMID- 21942473
TI  - Temperature and relative humidity dependency of film formation of polymeric latex
      dispersions.
AB  - Thermogravimetric analysis and a synchrotron small-angle X-ray scattering
      technique were employed to characterize the structural evolution of a polymeric
      latex dispersion during the first three stages of film formation at different
      temperatures and relative humidities. Three intermediate stages were identified:
      (1) stage I*, (2) stage I**, and (3) stage II*. Stage I* is intermediate to the
      conventionally defined stages I and II, where latex particles began to
      crystallization. The change of drying temperature affects the location of the
      onset of ordering, whereas relative humidity does not. Stage I** is where the
      latex particles with their diffuse shell of counterions in the fcc structure are
      in contact with each other. The overlapping of these layers results in an
      acceleration of the lattice shrinkage due to a decrease of effective charges.
      Stage II* is where the latex particles, dried well above their T(g), are deformed
      and packed only partially during film formation due to incomplete evaporation of
      water in the latex film. This is because of a rapid deformation of the soft latex
      particles at the liquid/air interface so that a certain amount of water is unable
      to evaporate from the latex film effectively. For a latex dispersion dried at a
      temperature close to its minimum film formation temperature, the transition
      between stages II and III can be continuous because the latex particles deform at
      a much slower rate, providing sufficient surface area for water evaporation.

PMID- 21942474
TI  - Does sunlight enhance the effectiveness of avian preening for ectoparasite
      control?
AB  - Preening is a bird's first line of defense against harmful ectoparasites.
      Ectoparasites, in turn, have evolved adaptations for avoiding preening such as
      hardened exoskeletons and escape behavior. Earlier work suggests that some groups
      of ectoparasites, such as feather lice, leave hiding places in feathers that are
      exposed to direct sunlight, making them more vulnerable to preening. It is,
      therefore, conceivable that birds may choose to preen in direct sunlight,
      assuming it improves the effectiveness of preening. Using mourning doves and
      their feather lice, we tested 2 related hypotheses; (1) that birds with access to
      direct sunlight preen more often than birds in shade, and (2) that birds with
      access to direct sunlight are more effective at controlling their ectoparasites
      than birds in shade. To test these hypotheses, we conducted an experiment in
      which we manipulated both sunlight and preening ability. Our results provided no
      support for either hypothesis, i.e., birds given the opportunity to preen in
      direct sunlight did not preen significantly more often, or more effectively, than
      did birds in shade. Thus, the efficiency of preening for ectoparasite control
      appears to be independent of light intensity, at least in the case of mourning
      doves and their feather lice.

PMID- 21942475
TI  - Microfold-cell targeted surface engineered polymeric nanoparticles for oral
      immunization.
AB  - Present work was envisaged to develop novel M-cell targeted polymeric particles
      that are capable of protecting the antigen from harsh gastric conditions. Ulex
      europaeus agglutinin (UEA-1) lectin was anchored for selective delivery of
      antigen to gut-associated lymphoid tissue (GALT). In the present investigation,
      chitosan nanoparticles were prepared by ionic gelation followed by antigen
      (bovine serum albumin, BSA) adsorption. Developed nanoparticles were further
      coated by UEA-1 lectin conjugated alginate and characterized for size, shape,
      zeta-potential, entrapment efficiency, and in vitro release. The immunological
      response of the developed system were performed in Balb/c mice and compared with
      aluminium hydroxide gel-based conventional vaccine. Results indicated that
      immunization with UEA-1 lectin conjugated alginate-coated particles induces
      efficient systemic as well as mucosal immune responses against BSA compared to
      other formulations. Aluminium-based vaccine dominated throughout the study, while
      failed in case of mucosal antibody. Additionally, IgG1 and IgG2a isotypes were
      determined to confirm the TH1/TH2 mixed immune response. The developed
      formulation exhibited superior systemic response along with dominating mucosal
      immunity. These data demonstrate the potential of UEA-alginate-coated
      nanoparticles as effective delivery system via oral route.

PMID- 21942476
TI  - Learning and unlearning: is communication with minority patients about self or
      others?

PMID- 21942477
TI  - General overview of the theories used in assessment: AMEE Guide No. 57.
AB  - There are no scientific theories that are uniquely related to assessment in
      medical education. There are many theories in adjacent fields, however, that can
      be informative for assessment in medical education, and in the recent decades
      they have proven their value. In this AMEE Guide we discuss theories on expertise
      development and psychometric theories, and the relatively young and emerging
      framework of assessment for learning. Expertise theories highlight the multistage
      processes involved. The transition from novice to expert is characterised by an
      increase in the aggregation of concepts from isolated facts, through semantic
      networks to illness scripts and instance scripts. The latter two stages enable
      the expert to recognise the problem quickly and form a quick and accurate
      representation of the problem in his/her working memory. Striking differences
      between experts and novices is not per se the possession of more explicit
      knowledge but the superior organisation of knowledge in his/her brain and pairing
      it with multiple real experiences, enabling not only better problem solving but
      also more efficient problem solving. Psychometric theories focus on the validity
      of the assessment - does it measure what it purports to measure and reliability -
      are the outcomes of the assessment reproducible. Validity is currently seen as
      building a train of arguments of how best observations of behaviour (answering a
      multiple-choice question is also a behaviour) can be translated into scores and
      how these can be used at the end to make inferences about the construct of
      interest. Reliability theories can be categorised into classical test theory,
      generalisability theory and item response theory. All three approaches have
      specific advantages and disadvantages and different areas of application. Finally
      in the Guide, we discuss the phenomenon of assessment for learning as opposed to
      assessment of learning and its implications for current and future development
      and research.

PMID- 21942478
TI  - Medical education in Sweden.
AB  - Undergraduate medical education in Sweden has moved from nationally regulated,
      subject-based courses to programmes integrated either around organ systems or
      physiological and patho-physiological processes, or organised around basic
      medical science in conjunction with clinical specialities, with individual
      profiles at the seven medical schools. The national regulations are restricted to
      overall academic and professional outcomes. The 51/2 year long university
      undergraduate curriculum is followed by a mandatory 18 months internship,
      delivered by the County Councils. While quality control and accreditation for the
      university curriculum is provided by the Swedish National Agency for Higher
      Education, no such formal control exists for the internship; undergraduate
      medical education is therefore in conflict with EU directives from 2005. The
      Government is expected to move towards 6 years long university undergraduate
      programmes, leading to licence, which will facilitate international mobility of
      both Swedish and foreign medical students and doctors. Ongoing academic
      development of undergraduate education is strengthened by the Bologna process. It
      includes outcome (competence)-based curricula, university Masters level complying
      with international standards, progression of competence throughout the
      curriculum, student directed learning, active participation and roles in
      practical clinical education and a national assessment model to assure
      professional competence. In the near future, the dimensioning of Swedish
      undergraduate education is likely to be decided more by international demands and
      aspects of quality than by national demands for doctors.

PMID- 21942479
TI  - How we train undergraduate medical students in decoding patients' nonverbal
      clues.
AB  - BACKGROUND: Communication skills (CS) and the psychosocial dimensions of patient
      care are currently considered core competencies in medical schools. CS programs
      have focused on verbal communication rather than the nonverbal communication.
      AIM: To present a training program aimed to decode patients' nonverbal clues for
      second year medical students implemented at the School of Medicine of the
      Autonomous University of Barcelona. METHOD: A description of a theoretical
      framework, principles, general and specific goals, learning settings, strategies,
      skills, and assessment tools. RESULTS: A model of training for preclinical
      medical students in decoding patients' nonverbal clues is shown. The students
      have shown satisfaction with the program. CONCLUSIONS: The detection of patients'
      nonverbal clues can be regarded as a humanistic skill that can be defined,
      trained, and evaluated. The program can be transferable to other institutions on
      health sciences and adapted to other academic levels or, even, clinical
      specialties.

PMID- 21942480
TI  - Introducing a problem-based learning program: 12 tips for success.
AB  - BACKGROUND: Worldwide many universities are changing their curricula and
      introducing integrated problem-based learning (PBL) programs. However, the
      introduction of a PBL program is a demanding process and requires resources, a
      lot of planning, and organisation. AIMS: This article aims at providing practical
      tips for preparing a PBL program. It highlights key challenges to create such
      programs and offers possible solutions to common challenges encountered. METHODS:
      Personal experience in introducing PBL programs in several universities together
      with key principles highlighted in the literature have been presented and
      discussed in light of the current medical education research. RESULTS:
      Introducing an integrated PBL program requires continuous support from the Dean
      and the Vice Chancellor. An essential step in this process is preparation and
      engagement of the faculty so that academics and clinicians become aware of the
      rationales for the change and work as part of a team in the construction of the
      new program. Consulting with other Departments of Medical Education that have
      introduced PBL, may help in avoiding common mistakes and providing a practical
      advice. CONCLUSION: Although there is no panacea for the introduction of a PBL
      program, this article addresses keys for successful introduction of such
      programs.

PMID- 21942481
TI  - Teaching communication with ethnic minority patients: ten recommendations.
AB  - INTRODUCTION: Culturally competent communication is indispensable for medical
      practice in an ethnically diverse society. This article offers recommendations to
      teach such communication skills based on the experiences of members of a Dutch
      NMVO Special Interest Group on 'Diversity'. METHOD: A questionnaire with three
      open-ended questions on recommendations for training in culturally competent
      communication was sent to all members (n = 35). Returned questionnaires (n = 23)
      were analysed qualitatively with a thematic coding framework based on educational
      themes emerging from the data. RECOMMENDATIONS: All students need to be educated
      in culturally competent communication. Teachers should stimulate awareness of
      personal biases and an open attitude. Teach the three core communication skills,
      listening, exploring and checking, and offer practice with a professional
      interpreter. Knowledge content should focus on mechanisms relevant to various
      ethnic groups. Offer students a variety of experiences in a safe environment. All
      involved should be aware that stereotyping is a pitfall. DISCUSSION: Training in
      communication skills for consultation with ethnic minority patients cannot be
      separated from teaching issues of awareness and knowledge. The shared views on
      the content of these communication trainings are in line with general patient
      centred approaches. The development of proper training in this field demands
      specific efforts of those involved.

PMID- 21942482
TI  - Patterns of distress in US medical students.
AB  - BACKGROUND: How multiple forms of psychological distress coexist in individual
      medical students has not been formally studied. AIM: To explore the prevalence of
      various forms of distress in medical students and their relationship to recent
      suicidal ideation or serious thoughts of dropping out of school. METHODS: All
      medical students at seven US schools were surveyed with standardized instruments
      to evaluate burnout, depression, stress, mental quality of life (QOL), physical
      QOL, and fatigue. Additional items explored recent suicidal ideation and serious
      thoughts of dropping out of medical school. RESULTS: Nearly all (1846/2246, 82%)
      of medical students had at least one form of distress with 1066 (58%) having >=3
      forms of distress. A dose-response relationship was found between the number of
      manifestations of distress and recent suicidal ideation or serious thoughts of
      dropping out. For example, students with 2, 4, or 6 forms of distress were 5, 15,
      and 24 fold, respectively, more likely to have suicidal ideation than students
      with no forms of distress assessed. All forms of distress were independently
      associated with suicidal ideation or serious thoughts of dropping out on
      multivariable analysis. CONCLUSIONS: Most medical students experience >=1
      manifestation of distress with many experiencing multiple forms of distress
      simultaneously. The more forms of distress experienced the greater the risk for
      suicidal ideation and thoughts of dropping out of medical school.

PMID- 21942484
TI  - Implementation of an audience response system improves residents' attitudes
      toward required weekly conference.

PMID- 21942483
TI  - Student perspectives on patient educators as facilitators of interprofessional
      education.
AB  - BACKGROUND: There has been increasing interest in the active involvement of
      patients in the education of health professionals. Few have examined the
      potential role of patient educators in the facilitation of interprofessional
      education (IPE). AIM: This qualitative program evaluation examined students'
      perceptions of their learning in a patient-facilitated IPE event. METHODS: One
      hundred and forty two students from physiotherapy, occupational therapy,
      medicine, and nursing participated in a 2.5-h session in which they interviewed
      patient educators living with a variety of chronic illnesses about their
      experiences. Patient educators participated in a 3-h training session prior to
      the event. RESULTS: Content analyses of six focus group transcripts (n = 27) and
      critical incident questionnaires (n = 138) revealed that students felt this was a
      positive experience, recognized the importance of advocating for their
      professional role, and valued the interprofessional learning. Students also
      valued participation from a variety of health professions and felt that IPE
      should be mandatory for all. CONCLUSION: Results suggest that trained patient
      educators can effectively facilitate interprofessional interactions.

PMID- 21942485
TI  - eMedical teacher.

PMID- 21942487
TI  - Development and pilot testing of a reflective learning guide for medical
      education.
AB  - BACKGROUND: Reflection is increasingly incorporated into all levels of medical
      education but little is known about best practices for teaching and learning
      reflection. AIMS: To develop a literature-based reflective learning guide for
      medical education and conduct a pilot study to determine whether (1) guide use
      enhances medical students' reflective writing skills and (2) reflective scores
      correlate with participant demographics and satisfaction. METHODS: Guide
      development consisted of literature review, needs assessment, single institution
      survey, and educational leader consensus. The pilot cohort study compared
      professionalism reflections written with and without the guide by third-year
      medical students on their core obstetrics and gynecology rotation. Reflections
      were scored using a previously validated rubric. A demographics and satisfaction
      survey examined effects of gender and satisfaction, as well as qualitative
      analysis of optional written comments. Analyses used independent t-tests and
      Pearson's correlations. RESULTS: We developed a two-page, literature-based guide
      in clinical Subjective-Objective-Assessment-Plan (SOAP) note format. There was a
      statistically significant difference, p < 0.001, in the reflection scores between
      groups, but no effects of gender or satisfaction. Student satisfaction with the
      guide varied widely. CONCLUSIONS: A single exposure to a literature-based guide
      to reflective learning improved written reflections by third-year medical
      students.

PMID- 21942489
TI  - Does medical student willingness to practise peer physical examination translate
      into action?
AB  - BACKGROUND: Peer physical examination (PPE) is commonly used in clinical skills
      teaching to allow students to practice physical examination techniques on each
      other. Previous studies have demonstrated medical students' generally positive
      attitudes towards PPE, but the correlation between student attitude and actual
      practice of PPE has yet to be examined. AIM: To determine if a positive student
      attitude towards PPE leads to subsequent action. METHODS: The target population
      were MBBS I students (2006-2007 cohort) admitted to the Li Ka Shing Faculty of
      Medicine, The University of Hong Kong. Student attitude towards PPE and
      subsequent practice of PPE were assessed through self-completed written
      questionnaires before and after the compulsory Clinical Skills Programme (CSP).
      RESULTS: A total of 100/128 (78%) students completed both questionnaires, of
      which 83 (65%) could be linked to demographic data. All study participants were
      ethnically Chinese. A high level of willingness to conduct PPE persisted before
      and after the CSP for both male and female students. However, more than half of
      the students did not subsequently examine various non-intimate body regions of a
      fellow student during the CSP. Female students were more likely to exhibit
      attitude-behaviour inconsistency. CONCLUSION: The existing positive attitudes
      towards PPE need to be harnessed so that more students are encouraged to follow
      through and actually practise PPE, thus realizing the educational benefits of
      this activity. This may be done by ensuring that PPE is conducted in a safe
      setting while being conscientious of gender differences. Scheduled time and the
      use of a logbook may be useful to facilitate students practising PPE.

PMID- 21942488
TI  - A virtual surgery in general practice: evaluation of a novel undergraduate
      virtual patient learning package.
AB  - BACKGROUND: A suite of 10 online virtual patients developed using the IVIMEDS
      'Riverside' authoring tool has been introduced into our undergraduate general
      practice clerkship. These cases provide a multimedia-rich experience to students.
      Their interactive nature promotes the development of clinical reasoning skills
      such as discriminating key clinical features, integrating information from a
      variety of sources and forming diagnoses and management plans. AIMS: To evaluate
      the usefulness and usability of a set of online virtual patients in an
      undergraduate general practice clerkship. METHOD: Online questionnaire completed
      by students after their general practice placement incorporating the System
      Usability Scale questionnaire. RESULTS: There was a 57% response rate. Ninety
      five per cent of students agreed that the online package was a useful learning
      tool and ranked virtual patients third out of six learning modalities. Questions
      and answers and the use of images and videos were all rated highly by students as
      useful learning methods. The package was perceived to have a high level of
      usability among respondents. CONCLUSION: Feedback from students suggest that this
      implementation of virtual patients, set in primary care, is user friendly and
      rated as a valuable adjunct to their learning. The cost of production of such
      learning resources demands close attention to design.

PMID- 21942490
TI  - "A chance to show yourself" - how do applicants approach medical school admission
      essays?
AB  - BACKGROUND: Although essay questions are used in the admissions process in many
      medical schools, there has been little research on how applicants respond to
      essay questions. AIMS: The purpose of this study was to explore how applicants to
      medical school approach essay questions used in the selection process. METHODS:
      Qualitative analysis was conducted on 240 randomly selected essays written by
      individuals applying to a single Canadian medical school in 2007 using a modified
      grounded theory approach to develop a conceptual framework which was checked in
      interviews with applicants. RESULTS: Three core variables were identified:
      "balancing service and reward," "anticipating the physician role," and
      "readiness." We described the overall approach of applicants as "taking stock,"
      writing about their journeys to the selection process, their experiences of the
      process itself, and about their anticipated future in medicine. CONCLUSION: Our
      findings suggest a disconnect between the approach of the applicants (to "show
      themselves" and be selected as individuals) and the stated intent of the process
      (to select applicants based on "objective" criteria). Our findings raise
      important questions about how applicants represent themselves when applying for
      medical school and suggest that it is important to understand the applicant's
      point of view when developing questions for selection processes.

PMID- 21942491
TI  - Pre-training evaluation and feedback improve medical students' skills in basic
      life support.
AB  - BACKGROUND: Evaluation and feedback are two factors that could influence
      simulation-based medical education and the time when they were delivered
      contributes their different effects. AIM: To investigate the impact of pre
      training evaluation and feedback on medical students' performance in basic life
      support (BLS). METHODS: Forty 3rd-year undergraduate medical students were
      randomly divided into two groups, C group (the control) and pre-training
      evaluation and feedback group (E&F group), each of 20. After BLS theoretical
      lecture, the C group received 45 min BLS training and the E&F group was
      individually evaluated (video-taped) in a mock cardiac arrest (pre-training
      evaluation). Fifteen minutes of group feedback related with the students' BLS
      performance in pre-training evaluation was given in the E&F group, followed by a
      30-min BLS training. After BLS training, both groups were evaluated with one
      rescuer BLS skills in a 3-min mock cardiac arrest scenario (post-training
      evaluation). The score from the post-training evaluation was converted to a
      percentage and was compared between the two groups. RESULTS: The score from the
      post-training evaluation was higher in the E&F group (82.9 +/- 3.2% vs. 63.9 +/-
      13.4% in C group). CONCLUSIONS: In undergraduate medical students without
      previous BLS training, pre-training evaluation and feedback improve their
      performance in followed BLS training.

PMID- 21942492
TI  - Harassment of newly admitted undergraduates by senior students in a Faculty of
      Dentistry in Sri Lanka.
AB  - BACKGROUND: Harassment of new students by senior colleagues appears to be
      widespread in the industrialised countries. Although 'ragging' of new entrants to
      universities in Sri Lanka gets frequently publicised, its prevalence, severity
      and the consequences have not been documented. AIMS: This study aims to ascertain
      the extent of mistreatment of new dental students, the measures they take when
      harassed and any resulting negative effects. METHODS: We surveyed the year 2008
      Dental students using 80 statements dealing with verbal/emotional, sexual and
      physical harassment. Sixty five students (91.5%) responded anonymously indicating
      whether a specific action occurred, the degree to which it affected them and any
      action taken to deal with it. RESULTS: Fifty percent of students had experienced
      mistreatment. Verbal and emotional abuse was more frequent than sexual or
      physical. Eighteen percent experienced sexual harassment, with a significantly
      higher proportion of males than females reporting it. A fifth of the students had
      upsetting memories of the event. Eighty five percent of the respondents stated
      that they did not suffer any ethnic or racial discrimination. CONCLUSIONS:
      Emotional harassment of new students by the seniors is a pervasive, yet under
      reported problem. Definitive interventions need to be implemented to prevent
      untoward consequences that can undermine the educational goals of training.

PMID- 21942493
TI  - Using clinical vignettes to assess doctors' and medical students' ability to
      identify sociocultural factors affecting health and health care.
AB  - BACKGROUND: Methods are needed for assessing clinicians' cultural knowledge
      frameworks. METHOD: We used a mail survey containing four short clinical
      vignettes to explore respondents' ability to identify sociocultural factors
      affecting health and health care. Participants included 299 physicians working at
      the University Hospitals of Geneva, 156 private physicians, and all 134 local
      medical students in their clinical years. Twenty-one sociocultural "domains" were
      identified through inductive coding of responses. For each vignette, we obtained
      the sum of codes as a measure of the respondent's awareness of sociocultural
      factors that might affect care in this particular situation. As internal
      consistency was reasonably high (0.68), we computed a single total score as the
      sum of responses given to all four vignettes. RESULTS: Reponses correlated with
      factors that might be expected to impact clinicians' awareness of sociocultural
      factors affecting care. Medical students, females, respondents who had received
      cultural competence training, those with greater interest in caring for immigrant
      patients, and those with high self-assessed skills at exploring psychosocial and
      migration-related issues scored higher on the vignettes. CONCLUSIONS: Brief
      clinical vignettes appear to be a relevant and feasible method for exploring
      physicians' knowledge of social and cultural factors affecting health and health
      care.

PMID- 21942495
TI  - Selective memory retrieval can impair and improve retrieval of other memories.
AB  - Research from the past decades has shown that retrieval of a specific memory
      (e.g., retrieving part of a previous vacation) typically attenuates retrieval of
      other memories (e.g., memories for other details of the event), causing retrieval
      induced forgetting. More recently, however, it has been shown that retrieval can
      both attenuate and aid recall of other memories (K.-H. T. Bauml & A. Samenieh,
      2010). To identify the circumstances under which retrieval aids recall, the
      authors examined retrieval dynamics in listwise directed forgetting, context
      dependent forgetting, proactive interference, and in the absence of any induced
      memory impairment. They found beneficial effects of selective retrieval in
      listwise directed forgetting and context-dependent forgetting but detrimental
      effects in all the other conditions. Because context-dependent forgetting and
      listwise directed forgetting arguably reflect impaired context access, the
      results suggest that memory retrieval aids recall of memories that are subject to
      impaired context access but attenuates recall in the absence of such
      circumstances. The findings are consistent with a 2-factor account of memory
      retrieval and suggest the existence of 2 faces of memory retrieval.

PMID- 21942494
TI  - Overdistribution in source memory.
AB  - Semantic false memories are confounded with a second type of error,
      overdistribution, in which items are attributed to contradictory episodic states.
      Overdistribution errors have proved to be more common than false memories when
      the 2 are disentangled. We investigated whether overdistribution is prevalent in
      another classic false memory paradigm: source monitoring. It is. Conventional
      false memory responses (source misattributions) were predominantly
      overdistribution errors, but unlike semantic false memory, overdistribution also
      accounted for more than half of true memory responses (correct source
      attributions). Experimental control of overdistribution was achieved via a series
      of manipulations that affected either recollection of contextual details or item
      memory (concreteness, frequency, list order, number of presentation contexts, and
      individual differences in verbatim memory). A theoretical model was used to
      analyze the data (conjoint process dissociation) that predicts that (a)
      overdistribution is directly proportional to item memory but inversely
      proportional to recollection and (b) item memory is not a necessary precondition
      for recollection of contextual details. The results were consistent with both
      predictions.

PMID- 21942496
TI  - Illusory expectations can affect retrieval-monitoring accuracy.
AB  - The present study investigated how expectations, even when illusory, can affect
      the accuracy of memory decisions. Participants studied words presented in large
      or small font for subsequent memory tests. Replicating prior work, judgments of
      learning indicated that participants expected to remember large words better than
      small words, even though memory for these words was equivalent on a standard test
      of recognition memory and subjective judgments. Critically, we also included
      tests that instructed participants to selectively search memory for either large
      or small words, thereby allowing different memorial expectations to contribute to
      performance. On these tests we found reduced false recognition when searching
      memory for large words relative to small words, such that the size illusion
      paradoxically affected accuracy measures (d' scores) in the absence of actual
      memory differences. Additional evidence for the role of illusory expectations was
      that (a) the accuracy effect was obtained only when participants searched memory
      for the aspect of the stimuli corresponding to illusory expectations (size
      instead of color) and (b) the accuracy effect was eliminated on a forced-choice
      test that prevented the influence of memorial expectations. These findings
      demonstrate the critical role of memorial expectations in the retrieval
      monitoring process.

PMID- 21942498
TI  - Release of photoactivatable drugs from plasmonic nanoparticles for targeted
      cancer therapy.
AB  - Chemotherapy is an important modality in cancer treatment. The major challenges
      of recent works are to improve drug loading, increase selectivity to target
      cells, and control the precise release of drugs. In the present study, we devised
      a smart drug carrier, an aptamer/hairpin DNA-gold nanoparticle (apt/hp-Au NP)
      conjugate for targeted delivery of drugs. The DNA aptamer sgc8c, which possesses
      strong affinity for protein tyrosine kinase 7 (PTK7), abundantly expressed on the
      surface of CCRF-CEM (T-cell acute lymphoblastic leukemia) cells, was assembled
      onto the surface of Au NPs. The repeated d(CGATCG) sequence within the hpDNA on
      the Au NP surface was used for the loading of the anticancer drug doxorubicin
      (Dox). After optimization, 25 (+/-3) sgc8c and 305 (+/-9) Dox molecules were
      successfully loaded onto the AuNP (13 nm) surface. The binding capability of
      apt/hp-Au NP conjugates toward targeted cells was investigated by flow cytometry
      and atomic absorption spectroscopy, which showed that the aptamer-functionalized
      nanoconjugates were selective for targeting of cancer cells. A cell toxicity (3
      (4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H
      tetrazolium, MTT) assay also demonstrated that these drug-loaded nanoconjugates
      could kill targeted cancer cells more effectively than nontargeted (control)
      cells. Most importantly, when illuminated with plasmon-resonant light (532 nm),
      Dox:nanoconjugates displayed enhanced antitumor efficacy with few side effects.
      The marked release of Dox from these nanoconjugates in living cells was monitored
      by increasing fluorescence signals upon light exposure. In vitro studies
      confirmed that aptamer-functionalized hp-Au NPs can be used as carriers for
      targeted delivery of drugs with remote control capability by laser irradiation
      with high spatial/temporal resolution.

PMID- 21942499
TI  - Structural studies coupling X-ray diffraction and high-energy X-ray scattering in
      the UO2(2+)-HBr(aq) system.
AB  - The structural chemistry of uranium(VI) in concentrated aqueous hydrobromic acid
      solutions was investigated using both single crystal X-ray diffraction and
      synchrotron-based high-energy X-ray scattering (HEXS) to reveal the structure of
      the uranium(VI) complexes in solution prior to crystallization. The crystal
      structures of a series of uranyl tetrabromide salts are reported, including
      Cs(2)UO(2)Br(4), Rb(2)UO(2)Br(4).2H(2)O, K(2)UO(2)Br(4).2H(2)O, and
      (NH(4))(2)UO(2)Br(4).2H(2)O, as well as a molecular dimer of uranium(VI),
      (UO(2))(2)(OH)(2)Br(2)(H(2)O)(4). Limited correspondence exists between the
      structures observed in the solid state and those in solution. Quantitative
      analysis of the HEXS data show an average U-Br coordination number of 1.9(2) in
      solution, in contrast to the U-Br coordination number of 4 in the solid salts.

PMID- 21942497
TI  - Protective effect of alpha-mangostin on cardiac reperfusion damage by attenuation
      of oxidative stress.
AB  - This study was designed to investigate if alpha-mangostin (alpha-M), a xanthone
      present in the pericarp of Garcinia mangostana L., was able to protect against
      reperfusion injury in Langendorff-reperfused hearts. It was observed that alpha-M
      maintains the cardiac mechanical work, diminishes the area of infarct, and
      prevents the decrease in cardiac ATP and phosphocreatine levels in the reperfused
      myocardium. The protective effect of this xanthone was associated with reduction
      of oxidative stress. alpha-M treatment prevented reperfusion injury-induced
      protein oxidation (protein carbonyl content), lipid peroxidation (malondialdehyde
      and 4-hydroxynonenal content), and diminution of glutathione content. In fact,
      after alpha-M treatment, the values in these parameters were comparable to those
      obtained in nonreperfused hearts. In summary, alpha-M induces a protective effect
      in postischemic heart associated to the prevention of oxidative stress secondary
      to reperfusion injury.

PMID- 21942500
TI  - Leapfrog cracking and nanoamorphization of ZnO nanowires during in situ
      electrochemical lithiation.
AB  - The lithiation reaction of single ZnO nanowire (NW) electrode in a Li-ion
      nanobattery configuration was observed by in situ transmission electron
      microscopy. Upon first charge, the single-crystalline NW was transformed into a
      nanoglass with multiple glassy nanodomains (Gleiter, H. MRS Bulletin2009, 34,
      456) by an intriguing reaction mechanism. First, partial lithiation of
      crystalline NW induced multiple nanocracks ~70 nm ahead of the main lithiation
      front, which traversed the NW cross-section and divided the NW into multiple
      segments. This was followed by rapid surface diffusion of Li(+) and solid-state
      amorphization along the open crack surfaces. Finally the crack surfaces merged,
      leaving behind a glass-glass interface (GGI). Such reaction front instability
      also repeated in the interior of each divided segment, further subdividing the NW
      into different nanoglass domains (nanoamorphization). Instead of the profuse
      dislocation plasticity seen in SnO(2) NWs (Science2010, 330, 1515), no
      dislocation was seen and the aforementioned nanocracking was the main precursor
      to the electrochemically driven solid-state amorphization in ZnO. Ab initio
      tensile decohesion calculations verified dramatic lithium embrittlement effect in
      ZnO, but not in SnO(2). This is attributed to the aliovalency of Sn cation
      (Sn(IV), Sn(II)) in contrast to the electronically more rigid Zn(II) cation.

PMID- 21942501
TI  - The role of family experiences and ADHD in the early development of oppositional
      defiant disorder.
AB  - OBJECTIVE: The present study examined the role of family experiences in the early
      development and maintenance of oppositional defiant disorder (ODD) symptoms in
      preschool-age children with behavior problems. METHOD: Participants were 199 3
      year-old children with behavior problems who took part in 4 annual child and
      family assessments. RESULTS: Children with behavior problems who were exposed to
      overreactive parenting practices, maternal depression, marital conflict, and
      lower family income tended to have more ODD symptoms 3 years later. Moreover,
      initial changes in paternal overreactivity and changes in maternal depression
      corresponded to initial changes in ODD symptoms. Children who met criteria for
      attention-deficit/hyperactivity disorder at 6 years of age were less likely to
      show improvement in ODD symptoms from 3 to 6 years of age, and they were more
      likely to have been exposed to negative parenting practices, marital conflict,
      and parental depression during the preschool years. Maternal depression and
      overreactivity mediated the relation between early hyperactivity and later ODD
      symptoms. CONCLUSIONS: Results point to the importance of early family
      functioning in the development of ODD.

PMID- 21942502
TI  - Observed communication in couples two years after integrative and traditional
      behavioral couple therapy: outcome and link with five-year follow-up.
AB  - OBJECTIVE: To examine changes in observed communication after therapy termination
      in distressed couples from a randomized clinical trial. METHOD: A total of 134
      distressed couples were randomly assigned to either traditional behavioral couple
      therapy (TBCT; Jacobson & Margolin, 1979) or integrative behavioral couple
      therapy (IBCT; Jacobson & Christensen, 1998). Videotaped samples of each couple's
      interactions were coded from pre-therapy, post-therapy, and 2-year follow-up
      assessments. At these 3 time points, each partner chose 1 current relationship
      problem to discuss. Relationship satisfaction was assessed at 2-year follow-up,
      and clinically significant treatment response and marital status were assessed 5
      years after treatment. RESULTS: Observed negativity and withdrawal decreased from
      therapy termination through the 2-year follow-up as expected, but problem solving
      did not change, and observed positivity decreased. IBCT produced superior changes
      from post-therapy to the 2-year follow-up assessment compared with TBCT. Post
      therapy levels and changes in communication over follow-up were associated with
      wife satisfaction at 2-year follow-up; only post-therapy to 2-year follow-up
      changes in communication were associated with husband satisfaction at 2-year
      follow-up. Post-therapy levels of problem solving and changes in wives'
      positivity from pre-therapy to post-therapy were associated with 5-year
      relationship outcomes. We found some counterintuitive results with positivity,
      but they were no longer significant after controlling for withdrawal.
      CONCLUSIONS: We found support for improvements in observed communication
      following treatment termination, with IBCT demonstrating greater maintenance of
      communication improvement over follow-up. We found limited evidence of
      associations between communication and relationship outcomes at 5-year follow-up.

PMID- 21942506
TI  - Intracoronary versus intravenous abciximab administration in STEMI patients:
      overview of current status and open questions.
AB  - OBJECTIVES: To perform a systematic review to provide rationale for intracoronary
      (IC) abciximab administration in patients with ST-segment elevation myocardial
      infarction (STEMI), to summarize recent studies comparing IC vs. intravenous (IV)
      abciximab administration in this setting and to define questions that need to be
      answered in future trials determining the optimal abciximab regimen. METHODS: A
      search covering the period from January 1993 to June 2011 was conducted by two
      independent investigators using MEDLINE, CENTRAL and Google Scholar databases.
      Proceedings from the scientific sessions of ACC, AHA, ESC, TCT and EuroPCR were
      also considered. RESULTS: IC administration allows one to obtain a much higher
      concentration of abciximab than IV injection at the culprit lesion. Therefore it
      is hypothesized that IC abciximab administration provides more efficient GP
      IIb/IIIa receptor inhibition and more pronounced additional dose-dependent
      antiplatelet, antithrombotic, and anti-inflammatory effects when compared to the
      IV route. Numerous observational and randomized studies comparing IC vs. IV
      abciximab in STEMI patients indicated improvement in different surrogate end
      points (infarct size, obstruction of coronary microcirculation, ST segment
      resolution, inflammatory mediators and markers of platelet activation) related to
      IC administration. The evidence supporting clinical benefits associated with IC
      injection of abciximab comes from one randomized and several non-randomized
      trials as most of the studies were underpowered to assess clinical outcomes. No
      difference in bleeding complications was observed between IC and IV regimens.
      Issues that need to be addressed in future studies include: the use of IC
      abciximab in combination with thrombectomy, the role of selective delivery
      systems, and the necessity of a prolonged IV infusion of abciximab after IC bolus
      administration. CONCLUSIONS: An accumulating body of evidence suggests the
      superiority of IC over IV abciximab administration in STEMI patients. However,
      further trials are warranted to establish the optimal strategy of abciximab
      treatment in this setting.

PMID- 21942510
TI  - Effect of silica and hydroxyapatite mineralization on the mechanical properties
      and the biocompatibility of nanocomposite collagen scaffolds.
AB  - A recently established materials concept of biomimetic composites based on
      silica, collagen, and calcium phosphates was adapted for the preparation of
      porous scaffolds suitable for tissue engineering applications. Mineralization was
      achieved by directed nucleation of silica on the templating organic phase during
      a sol-gel process with or without addition of hydroxyapatite. Both mineral phases
      (25 wt %, individually or combined in equal shares) influenced the scaffold's
      morphology at the nanoscale. Enhancement of apparent density and compressive
      strength was similar for silica or hydroxyapatite mineralization; however the
      stiffening effect of hydroxyapatite was much higher. All scaffold modifications
      provided proper conditions for adhesion, proliferation, and osteogenic
      differentiation of human bone marrow stromal cells. The open porosity allowed
      cells to migrate throughout the scaffolds while maintaining their viability, both
      confirmed by MTT staining and confocal laser scanning microscopy. Initial cell
      distributions were graduated due to collagen mineralization, but balanced out
      over the cultivation time of 28 days. RT-PCR analyses revealed higher gene
      expression of ALP but lower expression of BSP II and osteocalcin because of
      collagen mineralization. The results demonstrate that both silica and
      hydroxyapatite offer comparable possibilities to tailor mechanical properties of
      collagen-based scaffolds without being detrimental to in vitro biocompatibility.

PMID- 21942511
TI  - Target-specific cellular uptake of folate-decorated biodegradable polymer
      micelles.
AB  - For cancer therapy, folate (FA) and beta-cyclodextrin (beta-CD) decorated
      micelles based on the biodegradable pluronic F127-b-poly(epsilon-caprolactone)
      copolymer were fabricated. These micelles were measured by dynamic light
      scattering measurements and atomic force microscopy. The in vitro release of
      doxorubicin hydrochloride (DOX.HCl) from the biodegradable polymer micelles was
      performed in a phosphate-buffered saline solution at pH 7.4 and acetate buffer
      solution at pH 5.0 at the temperatures of 4, 25, and 37  degrees C, and the
      results show that the release was obviously influenced by the pH and temperature.
      The material cytotoxicity and the tumor cell growth inhibition assays of DOX.HCl
      loaded micelles were studied with the human hepatoblastoma cell line (HepG2), the
      lung epithelial cancer cell line (A549), and human nasopharyngeal epidermoid
      carcinoma cells (KB) and fibroblast normal cells using fluorescence microscopy as
      well as confocal laser scanning microscopy. The cellular uptake was
      quantitatively analyzed to further evaluate the active targeting behaviors of the
      micelles by flow cytometry. These quantitative and qualitative results of
      cellular uptake of the micelles provide evidence for the different targeting
      efficiencies of FA decoration for HepG2, KB, and A549 tumor cells as well as
      fibroblast normal cells. It also suggested that FA- and beta-CD-decorated
      doxorubicin-loaded micelles may have great potential as nanocarriers for targeted
      drug delivery.

PMID- 21942512
TI  - Role of structural order and excess energy on ultrafast free charge generation in
      hybrid polythiophene/Si photovoltaics probed in real time by near-infrared
      broadband transient absorption.
AB  - Despite the central role of light absorption and the subsequent generation of
      free charge carriers in organic and hybrid organic-inorganic photovoltaics, the
      precise process of this initial photoconversion is still debated. We employ a
      novel broadband (UV-Vis-NIR) transient absorption spectroscopy setup to probe
      charge generation and recombination in the thin films of the recently suggested
      hybrid material combination poly(3-hexylthiophene)/silicon (P3HT/Si) with 40 fs
      time resolution. Our approach allows for monitoring the time evolution of the
      relevant transient species under various excitation intensities and excitation
      wavelengths. Both in regioregular (RR) and regiorandom (RRa) P3HT, we observe an
      instant (<40 fs) creation of singlet excitons, which subsequently dissociate to
      form polarons in 140 fs. The quantum yield of polaron formation through
      dissociation of delocalized excitons is significantly enhanced by adding Si as an
      electron acceptor, revealing ultrafast electron transfer from P3HT to Si. P3HT/Si
      films with aggregated RR-P3HT are found to provide free charge carriers in planar
      as well as in bulk heterojunctions, and losses are due to nongeminate
      recombination. In contrast for RRa-P3HT/Si, geminate recombination of bound
      carriers is observed as the dominant loss mechanism. Site-selective excitation by
      variation of pump wavelength uncovers an energy transfer from P3HT coils to
      aggregates with a 1/e transfer time of 3 ps and reveals a factor of 2 more
      efficient polaron formation using aggregated RR-P3HT compared to disordered RRa
      P3HT. Therefore, we find that polymer structural order rather than excess energy
      is the key criterion for free charge generation in hybrid P3HT/Si solar cells.

PMID- 21942513
TI  - A modified fetal heart rate tracing interpretation system for prediction of
      cesarean section.
AB  - OBJECTIVE: To investigate whether a modified version of the 2008 National
      Institute of Child Health and Human Development (NICHD) interpretation system
      upon admission decreases cesarean delivery risk. METHODS: This retrospective
      cohort study ascribed a modified category to the first 30 min of fetal heart rate
      (FHR) tracings in labor. Category I was divided into two subsets (Ia and Ib) by
      the presence of accelerations. Category II was divided into four subsets (IIa
      IId) based on baseline FHR, variability, response to stimulation and
      decelerations. Log-binomial regression was used to calculate risk ratios (RR) and
      95% confidence intervals (CI). RESULTS: A category was ascribed to 910 women.
      Most FHR tracings were Category Ia (65.8%), Ib (7.7%), IIb (11.8%) and IId
      (14.0%). Category Ib tracings (fewer than two accelerations) were 2.26 (95% CI:
      1.13-4.52) times more likely to result in cesarean delivery for abnormal FHR
      tracing than Category Ia tracings. A similar increase in risk was seen when
      comparing Category IIb and Category IId with Category Ia. CONCLUSION: Application
      of a modified version of the 2008 NICHD FHR interpretation system to the initial
      30 min of labor can identify women at increased risk of cesarean delivery for
      abnormal FHR tracing.

PMID- 21942514
TI  - Is there a future for multiplexed technologies in the point-of-care setting?

PMID- 21942515
TI  - Dynamic range compression: a solution for proteomic biomarker discovery?

PMID- 21942516
TI  - Enantiomeric purity of chiral derivatizing reagents for enantioresolution.

PMID- 21942518
TI  - Conference report: current bioanalytical topics from the ASMS conference 2011.
AB  - The American Society For MS annual conference, the largest meeting for the MS
      related topics, has welcomed its 59th birthday. The conference was well attended
      (over 6600 attendees) from academy, government and industry. In addition to 336
      oral presentations from 56 sessions, 2820 posters were presented. Preceding the
      main conference, tutorial short courses ran on both Saturday and Sunday. There
      were 11 2-day and two 1-day short courses. The short courses were well
      diversified and well suited for scientists working in various fields related to
      MS. Various workshops (total 28) on specific topics were also well organized on
      Monday, Tuesday and Wednesday. There were 60 bioanalysis-related positions posted
      at the Employment Center - approximately 20 positions from CROs and the rest
      mainly from pharmaceutical and biotech companies.

PMID- 21942520
TI  - Impact of sample hemolysis on drug stability in regulated bioanalysis.
AB  - Being regulated by agencies' guidances, the importance of a robust validated
      bioanalytical method is crucial as it may impact the validity of the
      pharmacokinetic data generated. During blood collection and processing, the
      presence of hemolyzed plasma samples may occur and as a result its impact must be
      investigated to ensure method robustness. Indeed, hemolyzed samples may affect
      the analyte recovery efficiency, as well as the chromatography. Furthermore, the
      stability of an analyte in hemolyzed plasma can be an issue as analyte
      degradation may occur. In this article we report two case studies where the
      analyte instability was a result of sample hemolysis. A description of the
      appropriate actions undertaken for the resolution of the issue will be discussed.

PMID- 21942519
TI  - 2011 White paper on recent issues in bioanalysis and regulatory findings from
      audits and inspections.
AB  - The 5th Workshop on Recent Issues in Bioanalysis (WRIB) was organized by the
      Calibration and Validation Group as a 2-day full immersion workshop for
      pharmaceutical companies, CROs and regulatory agencies to discuss, review, share
      perspectives, provide potential solutions and agree upon a consistent approach to
      recent issues in the bioanalysis of both small and large molecules. High quality,
      better compliance to regulations and scientific excellence are the foundation of
      this workshop. As in the previous editions of this significant event,
      recommendations were made and a consensus was reached among panelists and
      attendees, including industry leaders and regulatory experts representing the
      global bioanalytical community, on many 'hot' topics in bioanalysis. This 2011
      White Paper is based on the conclusions from this workshop, and aims to provide a
      practical reference guide on those topics.

PMID- 21942521
TI  - Evaluation of two ELISA methods to detect therapeutic anti-IGF1R antibodies in
      clinical study samples of dalotuzumab.
AB  - BACKGROUND: Dalotuzumab (MK 0646), an anti-IGF1R antibody intended for cancer
      therapy, has progressed to Phase III clinical trials. To evaluate pharmacokinetic
      properties, we developed and compared two ELISAs to measure dalotuzumab in human
      serum and validated the second method following regulatory guidelines for ligand
      binding assays. RESULTS: After an IGF1R-mediated capture step, dalotuzumab was
      detected by either an antihuman IgGFc- or by an antihuman IgG1-specific antibody.
      The assay range was 20 to 2000 ng/ml with mean inter-day accuracy of controls
      ranging from 97 to 108% (method A) and 83 to 97% (method B), respectively. Mean
      assay precision was <=20% CV both intra- and inter-day. Other parameters that
      were validated included dilution linearity, stability, interferences and incurred
      sample reanalysis. In addition, application of both assay formats to clinical
      sample analysis was demonstrated establishing time-concentration curves.
      CONCLUSION: As the methods rely on commercial reagents, they may be applicable to
      other anti-IGF1R antibodies and facilitate the development of new therapeutics.

PMID- 21942522
TI  - Identification and subsequent removal of an interference by FAIMS in the
      bioanalysis of dianicline in animal plasma.
AB  - BACKGROUND: The determination of pharmacokinetic parameters requires accurate and
      reliable bioanalytical methods. Even using highly selective MS/MS, interferences
      can occur. This paper describes the source of some of these interferences with an
      example discussed involving the problem of a ketamine interference in a plasma
      assay. RESULTS: The introduction of field asymmetric waveform ion mobility
      spectrometry (FAIMS) removed the interference, enhanced signal-to-background and
      met GLP acceptance criteria. Relative to the non-FAIMS method, assay calibration
      characteristics were improved. The FAIMS source gave optimal performance
      following the introduction of a split in order to reduce the inlet flow to
      approximately 0.4 ml/min. CONCLUSION: The introduction of ion-mobility separation
      into a bioanalytical LC-MS/MS method can remove unexpected isobaric interferences
      without the need to redevelop the chromatography.

PMID- 21942523
TI  - Biomarker analysis for prostate cancer diagnosis using LC-MS and CE-MS.
AB  - Prostate cancer is one of the most common cancer types in men. In addition, it is
      the second leading cause of cancer death in the USA and Canada. Prostate cancer
      diagnosis is not a precise science yet. Discovery of potential biomarkers for
      early prostate cancer diagnosis and monitoring is crucially important. LC-MS and
      CE-MS have been widely used analytical techniques in the biomarker discovery.
      This review will describe the applications of LC-MS with different ionization
      techniques, such as ESI, atmospheric-pressure photoionization and atmospheric
      pressure chemical ionization, and CE-MS techniques used in prostate cancer
      biomarker analysis.

PMID- 21942524
TI  - Method transfer for ligand-binding assays: recommendations for best practice.
AB  - To support clinical trials, bioanalytical methods are often transferred from one
      laboratory to another. With the rising number of large-molecule therapeutic
      proteins submitted for US FDA approval, the demand for large-molecule
      bioanalytical support and, subsequently, method transfer increases. Ligand
      binding assays are the methods most commonly used to quantify endogenous and
      therapeutic proteins for the assessment of biomarkers and pharmacokinetic
      parameters. The goal of this review is to provide an overview of ligand-binding
      assay method transfer, essential parameters for partial method validation and to
      lay out a strategy to increase the chance of success. The recommendations herein
      are based on a summary of current publications and the authors' specific
      experiences, to help increase workload efficiency, maintain positive
      collaborations with partners and meet program timelines.

PMID- 21942526
TI  - Mechanisms of function and disease of natural and replacement heart valves.
AB  - Over the past several decades, there has been substantial progress toward
      understanding the mechanisms of heart valve function and dysfunction. This review
      summarizes an evolving conceptual framework of heart valve functional structure,
      developmental biology, and pathobiology and explores the implications of key
      insights. I emphasize: (a) valve cell and extracellular matrix biology and the
      impact of biomechanical factors on function, homeostasis, environmental
      adaptation, and key pathological processes; (b) the role of developmental
      processes, valvular cell behavior, and extracellular matrix remodeling in
      congenital and acquired valve abnormalities; and (c) the cell/matrix biology of
      degeneration in replacement tissue valves. I also summarize how these
      considerations may ultimately inform the potential for prevention and treatment
      of major diseases and potentially therapeutic regeneration of the cardiac valves.
      Recent advances and opportunities for research and clinical translation are
      highlighted.

PMID- 21942529
TI  - Recent advances in ligand targeted therapy.
AB  - BACKGROUND: Ligand targeted therapy (LTT) is a powerful pharmaceutical strategy
      to achieve selective drug delivery to pathological cells, for both therapeutic
      and diagnostic purposes, with the advantage of limited side effects and toxicity.
      This active drug targeting approach is based on the discovery that there are
      receptors overexpressed on pathological cells, compared to their expression in
      normal tissues. PURPOSE: The purpose of this article is to review recently
      published data on LTT with applications, both in the field of cancer therapy and
      other diseases. Moreover, data on LTT exploiting receptors overexpressed at
      cytoplasmatic level are also reviewed. METHODS: Data were deduced from Medline
      (PubMed) and SciFinder and their selections were made with preference to papers
      where the most relevant receptors were involved. RESULTS: Several groups have
      reported improved delivery of targeted nanocarriers, as compared to nontargeted
      ones, to pathological cells. LTT offers several advantages, but there are also
      limitations in the development of this strategy. Moreover, LTT have shown
      encouraging results in in vitro and in animal models in vivo; hence their
      clinical potential awaits investigation. CONCLUSION: Recent studies highlight
      that the ligand density plays an important role in targeting efficacy.
      Furthermore, LTT applications in diseases different from cancer and those
      exploiting receptors overexpressed at cytoplasmatic level are growing.

PMID- 21942527
TI  - Molecular pathogenesis of Ewing sarcoma: new therapeutic and transcriptional
      targets.
AB  - Approximately one-third of sarcomas contain specific translocations. Ewing
      sarcoma is the prototypical member of this group of sarcomas; it was the first to
      be recognized pathologically as a singular entity and to have its signature
      translocation defined cytogenetically, which led to the identification of its key
      driver alteration, the EWS-FLI1 gene fusion that encodes this aberrant, chimeric
      transcription factor. We review recent progress in selected areas of Ewing
      sarcoma research, including the application of genome-wide chromatin
      immunoprecipitation analyses, to provide a comprehensive view of the EWS-FLI1
      target gene repertoire, the identification of EWS-FLI1 target genes that may also
      point to therapeutically targetable pathways, and data from model systems as they
      relate to the elusive cell of origin of Ewing sarcoma and its possible
      similarities to mesenchymal stem cells.

PMID- 21942528
TI  - Merkel cell carcinoma: a virus-induced human cancer.
AB  - Merkel cell polyomavirus (MCV) is the first polyomavirus directly linked to human
      cancer, and its recent discovery helps to explain many of the enigmatic features
      of Merkel cell carcinoma (MCC). MCV is clonally integrated into MCC tumor cells,
      which then require continued MCV oncoprotein expression to survive. The
      integrated viral genomes have a tumor-specific pattern of tumor antigen gene
      mutation that incapacitates viral DNA replication. This human cancer virus
      provides a new model in which a common, mostly harmless member of the human viral
      flora can initiate cancer if it acquires a precise set of mutations in a host
      with specific susceptibility factors, such as age and immune suppression.
      Identification of this tumor virus has led to new opportunities for early
      diagnosis and targeted treatment of MCC.

PMID- 21942530
TI  - High optical quality InP-based nanopillars fabricated by a top-down approach.
AB  - Dense and uniform arrays of InP-based nanopillars were fabricated by dry etching
      using self-assembly of colloidal silica particles for masking. The pillars, both
      single and arrays, fabricated from epitaxially grown InP and InP/GaInAsP/InP
      quantum well structures show excellent photoluminescence (PL) even at room
      temperature. The measured PL line widths are comparable to the as-grown wafer
      indicating high quality fabricated pillars. A stamping technique enables transfer
      with arbitrary densities of the nanopillars freed from the substrate by
      selectively etching a sacrificial InGaAs layer.

PMID- 21942531
TI  - Needle-free subcutaneous sumatriptan for triptan users requiring a change in
      migraine therapy: efficacy and impact on patient-rated functionality,
      satisfaction, and confidence.
AB  - OBJECTIVE: To evaluate efficacy of, satisfaction with, and confidence in SDP
      (SUMAVEL DosePro *) among triptan users requiring a change in therapy. SDP is a
      needle-free, subcutaneous sumatriptan product that confers relief as early as 10
      minutes postdose. RESEARCH DESIGN AND METHODS: In an open-label study, SDP was
      administered for <=4 migraine attacks over <=60 days by migraineurs currently
      treated with triptans (any form/dosage). In the 90 patients with baseline
      Migraine-ACT scores <=2 (indicating the need for a change in therapy), efficacy
      data were collected from patient diaries, and satisfaction was measured with the
      revised Patient Perception of Migraine Questionnaire (PPMQ-R). CLINICAL TRIAL
      REGISTRATION NUMBER: NCT01016834 on clinicaltrials.gov. RESULTS: Across all
      attacks, the rates of pain relief were 30.7%, 66.4%, 80.1%, 81.6%, and 77.6% at
      0.25, 0.5, 1, 2, and 24 hours postdose, respectively. Corresponding results for
      pain-free response were 0.7%, 14.8%, 35.0%, 48.0, and 65.7%. Sustained 24-hour
      pain relief was observed in 61.0% of attacks. PPMQ-R scores (transformed to 0-100
      scales, mean +/- SD) improved from baseline to end of treatment for Efficacy
      (52.5 +/- 17.8 versus 74.8 +/- 23.4, p < 0.0001) and Functionality (46.2 +/- 22.3
      versus 71.3 +/- 25.2, p < 0.0001) with no deterioration in Tolerability (80.6 +/-
      14.7 versus 83.5 +/- 17.7, p = 0.12). PPMQ-R Overall Satisfaction score increased
      from baseline to end of treatment (55.1 +/- 23.2 versus 74.6 +/- 27.7, p <
      0.0001). The percentage of patients (90% confidence interval) confident or very
      confident in treating migraine attacks increased from 22.2% (15.2, 30.6) at
      baseline to 57.8% (48.6, 66.6) at end of treatment. Results should be interpreted
      in the context of the open-label design of the original study. CONCLUSION: With
      SDP, triptan users requiring a change in therapy experienced increased efficacy,
      satisfaction with therapy, and confidence in treatment without deterioration in
      tolerability.

PMID- 21942535
TI  - Characterization of perylene diimide dye self-assemblies and their use as
      templates for the synthesis of hybrid and supermicroporous nanotubules.
AB  - The self-organizing structures formed by a water-soluble perylene diimide dye
      (PDI) have been studied by several experimental techniques as potential templates
      for the preparation of hybrid nanomaterials. The dye forms chromonic-nematic and
      hexagonal liquid crystals in water. The aggregates in liquid crystals consist of
      one-molecule-wide stacks. From the changes in the solution proton NMR chemical
      shifts with concentration, it appears that adjacent molecules are twisted. There
      is significant broadening of the aromatic resonances at higher concentrations,
      arising from nonmotionally averaged dipole-dipole coupling between adjacent
      aromatic hydrogens. This is attributed to slow overall rotation of the aggregates
      in solution, suggesting that they grow up to several tens of nanometers. Dye
      aggregates serve as templates for the formation of silica tubules (1-5 MUm
      length, average diameter ~300 nm), with aligned and very thin (1-2 nm) dye
      nanostripes embedded in the walls. The silica tubes precipitated from solution
      are formed by the cooperative interaction between PDI and silica species during
      the sol-gel reaction. Upon calcination, silica nanotubules with supermicroporous
      walls are obtained. In comparison with conventional surfactant systems, the use
      of pi-pi stacked chromonic aggregates brings new possibilities for the templated
      fabrication of pores with sizes below the mesoporous range. Materials could find
      applications in photovoltaics as well as in shape selective catalysis and
      adsorption.

PMID- 21942532
TI  - Pulmonary toxicity of well-dispersed single-wall carbon nanotubes after
      inhalation.
AB  - Single-wall carbon nanotubes (SWCNTs) were well-dispersed by ultrasonication to
      conduct an inhalation study. SWCNTs were generated using a pressurised nebuliser
      with liquid suspension of SWCNTs. Wistar rats were exposed to the well-dispersed
      SWCNT (diameter of bundle: 0.2 MUm; length of bundle: 0.7 MUm) for 4 weeks. The
      low and high mass concentrations of SWCNTs were 0.03 +/- 0.003 and 0.13 +/- 0.03
      mg/m(3), respectively. The rats were sacrificed at 3 days, 1 month, and 3 months
      after the end of exposure. There were no increases of total cell or neutrophil
      counts in the bronchoalveolar lavage fluid (BALF), or the concentration of
      cytokine-induced neutrophil chemoattractant in the lungs or BALF in both the high
      and low concentration-exposed groups. Pulmonary infiltration of neutrophils was
      not observed in either exposed group throughout the observation period. Well
      dispersed SWCNT did not induce neutrophil inflammation in the lung under the
      conditions in the present study.

PMID- 21942536
TI  - Molecular simulations of multimodal ligand-protein binding: elucidation of
      binding sites and correlation with experiments.
AB  - Multimodal chromatography, which employs more than one mode of interaction
      between ligands and proteins, has been shown to have unique selectivity and high
      efficacy for protein purification. To test the ability of free solution molecular
      dynamics (MD) simulations in explicit water to identify binding regions on the
      protein surface and to shed light on the "pseudo affinity" nature of multimodal
      interactions, we performed MD simulations of a model protein ubiquitin in aqueous
      solution of free ligands. Comparisons of MD with NMR spectroscopy of ubiquitin
      mutants in solutions of free ligands show a good agreement between the two with
      regard to the preferred binding region on the surface of the protein and several
      binding sites. MD simulations also identify additional binding sites that were
      not observed in the NMR experiments. "Bound" ligands were found to be
      sufficiently flexible and to access a number of favorable conformations,
      suggesting only a moderate loss of ligand entropy in the "pseudo affinity"
      binding of these multimodal ligands. Analysis of locations of chemical subunits
      of the ligand on the protein surface indicated that electrostatic interaction
      units were located on the periphery of the preferred binding region on the
      protein. The analysis of the electrostatic potential, the hydrophobicity maps,
      and the binding of both acetate and benzene probes were used to further study the
      localization of individual ligand moieties. These results suggest that water
      mediated electrostatic interactions help the localization and orientation of the
      MM ligand to the binding region with additional stability provided by nonspecific
      hydrophobic interactions.

PMID- 21942537
TI  - Self-assembly and morphology control of new L-glutamic acid-based amphiphilic
      random copolymers: giant vesicles, vesicles, spheres, and honeycomb film.
AB  - New amphiphilic random copolymers containing hydrophobic dodecyl (C12) chain and
      hydrophilic L-glutamic acid were synthesized, and their self-assembly in solution
      as well as on the solid surfaces was investigated. The self-assembly behavior of
      these polymers are largely dependent on their hydrophilic and hydrophobic
      balances. The copolymer with a more hydrophobic alkyl chain (~90%) self-assembled
      into giant vesicles with a diameter of several micrometers in a mixed solvent of
      ethanol and water. When the hydrophobic ratio decreased to ca. 76%, the polymer
      self-assembled into conventional vesicles with several hundred nanometers. The
      giant vesicles could be fused in certain conditions, while the conventional
      vesicles were stable. When the content of the hydrophilic part was further
      increased, no organized structures were formed. On the other hand, when the
      copolymer solutions were directly cast on solid substrates such as silicon
      plates, films with organized nanostructures could also be obtained, the
      morphology of which depended on solvent selection. When ethanol or methanol was
      used, spheres were obtained. When dichloromethane was used as the solvent,
      honeycomb-like morphologies were obtained. These results showed that through
      appropriate molecular design, random copolymer could self-assemble into various
      organized structures, which could be regulated through the
      hydrophobic/hydrophilic balance and the solvents.

PMID- 21942543
TI  - Theoretical analysis of mechanistic pathways for hydrogen evolution catalyzed by
      cobaloximes.
AB  - The mechanistic pathways for hydrogen evolution catalyzed by cobalt complexes
      with supporting diglyoxime ligands are analyzed with computational methods. The
      cobaloximes studied are Co(dmgBF(2))(2) (dmg = dimethylglyoxime) and
      Co(dpgBF(2))(2) (dpg = diphenylglyoxime) in acetonitrile. The reduction
      potentials and pK(a) values are calculated with density functional theory in
      conjunction with isodesmic reactions, incorporating the possibility of axial
      solvent ligand loss during the reduction process. The solvent reorganization
      energies for electron transfer between the cobalt complex and a metal electrode
      and the inner-sphere reorganization energies accounting for intramolecular
      rearrangements and the possibility of ligand loss are also calculated. The
      relative reduction potentials agree quantitatively with the available
      experimental values. The pK(a)s and reorganization energies agree qualitatively
      with estimates based on experimental data. The calculations suggest that a peak
      measured at ca. -1.0 V vs SCE in cyclic voltammetry experiments for
      Co(dmgBF(2))(2) is more likely to correspond to the Co(II)H/Co(I)H reduction
      potential than the Co(III)H/Co(II)H reduction potential. The calculations also
      predict pK(a) values of Co-hydride complexes and reduction potentials for both
      cobaloximes that have not been determined experimentally. The results are
      consistent with a mechanism in which the Co(III) and Co(II) complexes have two
      axial solvent ligands and the Co(I) complex has a single axial ligand along the
      reaction pathway. Analysis of the free energy diagrams generated for six
      different monometallic and bimetallic hydrogen production pathways identified the
      most favorable pathways for Co(dmgBF(2))(2) and tosic acid. The thermodynamically
      favored monometallic pathway passes through a Co(III)H intermediate, and Co(II)H
      reacts with the acid to produce H(2). The thermodynamically favored bimetallic
      pathways also pass through the Co(III)H intermediate, but the pathways in which
      two Co(III)H or two Co(II)H complexes react to produce H(2) are not
      thermodynamically distinguishable with these methods. On the basis of the
      electrostatic work term associated with bringing the two cobalt complexes
      together in solution, the preferred bimetallic pathway involves the reaction of
      two Co(III)H complexes to produce H(2). This mechanistic insight is important for
      designing more effective catalysts for solar energy conversion.

PMID- 21942538
TI  - Assessing treatment motivation among patients receiving antiretroviral therapy: a
      multidimensional approach.
AB  - Using multidimensional scaling (MDS) analysis, this study examined how patient
      conceptualisations of treatment motivation compare with theoretically based
      assumptions used in current assessment approaches. Patients undergoing
      antiretroviral therapy for HIV/AIDS (n=39) rated for similarity between all
      possible pairings of 23 treatment descriptions, including descriptors of
      intrinsic, extrinsic, approach and avoidance motivation. MDS analyses revealed
      that patient perceptions of intrinsic and extrinsic motivations often differ from
      those based on definitions derived from common interpretations of self
      determination theory. Findings also showed that patients reported motivation for
      avoiding treatment when they associated their medication regimens with side
      effects and other negatively valenced outcomes. The study describes new
      applications of MDS in assessing how patients perceive the relationship between
      treatment behaviours and specific forms of motivation, such as intrinsic and
      extrinsic motivations. In addition, the study suggests how MDS may be used to
      develop behavioural strategies aimed at helping patients follow their regimens
      consistently by identifying treatment conceptualisations and contexts that
      facilitate or impede adherence.

PMID- 21942545
TI  - The three Rs and animal experimentation - documented signs of advancement, or of
      stagnation?

PMID- 21942544
TI  - Aqueous, protein-driven synthesis of transition metal-doped ZnS immuno-quantum
      dots.
AB  - The intentional introduction of transition metal impurities in semiconductor
      nanocrystals is an attractive approach for tuning quantum dot emission over a
      wide range of wavelengths. However, the development of effective doping
      strategies can be challenging, especially if one simultaneously requires a low
      toxicity crystalline core, a functional protein shell, and a "green", single-step
      synthesis process. Here, we describe a simple and environmentally friendly route
      for the biofabrication of Cu-doped (blue-green) or Mn-doped (yellow-orange) ZnS
      nanocrystals surrounded by an antibody-binding protein shell. The ZnS:Mn hybrid
      particles obtained with this method exhibit a 60% enhancement in maximum
      photoluminescence intensity relative to undoped nanocrystals and have a
      hydrodynamic diameter inferior to 10 nm. They can be stored for months at 4 
      degrees C, are stable over a physiological range of pH and salt concentrations,
      can be decorated with variable amounts of antibodies by direct mixing, and hold
      promise for biosensing and imaging applications.

PMID- 21942546
TI  - Vaginal irritation models: the current status of available alternative and in
      vitro tests.
AB  - Mucosal surfaces, such as the vaginal epithelium, are natural barriers to
      infection that are constantly exposed to bacteria and viruses, and are therefore
      potential sites of entry for numerous pathogens. The vaginal epithelium can be
      damaged mechanically, e.g. by the incorrect use of objects such as tampons, and
      by chemicals that are irritating or corrosive. Consequently, this can lead to an
      increase in susceptibility to further damage or infection. Pharmaceutical,
      cosmetic and personal care products that are specifically formulated for
      application onto human external mucosae can occasionally induce undesirable local
      or systemic side-effects. Therefore, the compatibility of applied materials with
      this mucosal surface represents a key issue to be addressed by manufacturers. The
      most frequently used method for assessing vaginal mucosal irritation is the in
      vivo rabbit vaginal irritation test. However, the current emphasis in the field
      of toxicology is to use alternative in vitro methods that reduce, refine, and
      replace the use of animals, and which model and predict human, not animal,
      responses. Such an approach is of particular interest to the personal care and
      cosmetic industries in their effort to comply with European legislative measures,
      such as the 7th Amendment to the EU Cosmetics Directive that does not permit the
      marketing of cosmetic products if they, or their ingredients, have been tested
      for irritation responses in animals. The focus of this review is to provide an
      overview of the alternative and in vitro tests that are currently available for
      vaginal mucosal irritation assessment, and which are already used, or may become
      useful, to establish the safety of newly-designed products for human use.

PMID- 21942547
TI  - Development of the EpiOcular(TM) eye irritation test for hazard identification
      and labelling of eye irritating chemicals in response to the requirements of the
      EU cosmetics directive and REACH legislation.
AB  - The recently implemented 7th Amendment to the EU Cosmetics Directive and the EU
      REACH legislation have heightened the need for in vitro ocular test methods. To
      address this need, the EpiOcular(TM) eye irritation test (EpiOcular-EIT), which
      utilises the normal (non-transformed) human cell-based EpiOcular tissue model,
      has been developed. The EpiOcular-EIT prediction model is based on an initial
      training set of 39 liquid and 21 solid test substances and uses a single exposure
      period and a single cut-off in tissue viability, as determined by the MTT assay.
      A chemical is classified as an irritant (GHS Category 1 or 2), if the tissue
      viability is <= 60%, and as a non-irritant (GHS unclassified), if the viability
      is > 60%. EpiOcular-EIT results for the training set, along with results for an
      additional 52 substances, which included a range of alcohols, hydrocarbons,
      amines, esters, and ketones, discriminated between ocular irritants and non
      irritants with 98.1% sensitivity, 72.9% specificity, and 84.8% accuracy. To
      ensure the long-term commercial viability of the assay, EpiOcular tissues
      produced by using three alternative cell culture inserts were evaluated in the
      EpiOcular-EIT with 94 chemicals. The assay results obtained with the initial
      insert and the three alternative inserts were very similar, as judged by
      correlation coefficients (r2) that ranged from 0.82 to 0.96. The EpiOcular-EIT
      was pre-validated in 2007/2008, and is currently involved in a formal, multi
      laboratory validation study sponsored by the European Cosmetics Association
      (COLIPA) under the auspices of the European Centre for the Validation of
      Alternative Methods (ECVAM). The EpiOcular-EIT, together with EpiOcular's long
      history of reproducibility and proven utility for ultra-mildness testing, make
      EpiOcular a useful model for addressing current legislation related to animal use
      in the testing of potential ocular irritants.

PMID- 21942548
TI  - In-house validation of the EpiOcular(TM) eye irritation test and its combination
      with the bovine corneal opacity and permeability test for the assessment of
      ocular irritation.
AB  - In 2009, the Bovine Corneal Opacity and Permeability (BCOP) test was accepted by
      the regulatory bodies for the identification of corrosive and severe ocular
      irritants (Global Harmonised System [GHS] Category 1). However, no in vitro test
      is currently accepted for the differentiation of ocular irritants (GHS Category
      2) and non-irritants (GHS No Category). Human reconstructed tissue models have
      been suggested for incorporation into a tiered testing strategy to ultimately
      replace the Draize rabbit eye irritation test (OECD TG 405). The purpose of this
      study was to evaluate whether the EpiOcular(TM) reconstructed cornea-like tissue
      model and the COLIPA pre-validated EpiOcular Eye Irritation Test (EpiOcular-EIT)
      could be used as suitable components of this testing strategy. The in-house
      validation of the EpiOcular-EIT was performed by using 60 test substances,
      including a broad variety of chemicals and formulations for which in vivo data
      (from the Draize rabbit eye irritation test) were available. The test substances
      fell into the following categories: 18 severe irritants/corrosives (Category 1),
      21 irritants (Category 2), and 21 non-irritants (No Category). Test substances
      that decreased tissue viability to <= 60% (compared to the negative control
      tissue) were considered to be eye irritants (Category 1/2). Test substances
      resulting in tissue viability of > 60% were considered to be non-irritants (No
      Category). For the assessed dataset and the classification cut-off of 60%
      viability, the EpiOcular-EIT provided 98% and 84% sensitivity, 64% and 90%
      specificity, and 85% and 86% overall accuracy for the literature reference and
      BASF proprietary substances, respectively. Applying a 50% tissue viability cut
      off to distinguish between irritants and non-irritants resulted in 93% and 82%
      sensitivity, 68% and 100% specificity, and 84% and 88% accuracy for the
      literature reference and BASF proprietary substances, respectively. Further, in
      the EpiOcular-EIT (60% cut-off), 100% of severely irritating substances under
      predicted by the BCOP assay were classified as Category 1/2. The results obtained
      in this study, based on 60 test substances, indicate that the EpiOcular-EIT and
      the BCOP assay can be combined in a testing strategy to identify strong/severe
      eye irritants (Category 1), moderate and mild eye irritants (Category 2), and non
      irritants (No Category) in routine testing. In particular, when the bottom-up
      strategy with the 60% viability cut-off was employed, none of the severely
      irritating substances (Category 1) were under-predicted to be non-irritant.
      Sensitivity for Category 1/2 substances was 100% for literature reference
      substances and 89% for BASF SE proprietary substances.

PMID- 21942549
TI  - The tenth anniversary of the Bjorn Ekwall memorial foundation.
AB  - The Bjorn Ekwall Memorial Foundation (BEMF) was initiated by the Scandinavian
      Society for Cell Toxicology in 2001, to honour the memory of Dr Bjorn Ekwall
      (1940-2000) and to establish a prize, the Bjorn Ekwall Memorial Award. The prize
      is awarded to scientists who have significantly contributed to the field of cell
      toxicology, and whose work is contributing toward the replacement of animal
      experiments by alternative toxicity tests. Over the past 10 years, the Bjorn
      Ekwall Memorial Award has been presented annually. Bjorn Ekwall, an outstanding
      Swedish cell toxicologist, was one of the pioneers in the development and
      application of alternative methods to animal tests in toxicology. All his
      scientific work was devoted to in vitro toxicology, and in particular, to the use
      of cultured human cells for the screening of toxic chemicals. In the middle of
      the 1980s, he initiated the international Multicentre Evaluation of In Vitro
      Cytotoxicity (MEIC) project, to evaluate the usefulness of in vitro tests for the
      estimation of human acute systemic toxicity. To prove his "basal cytotoxicity
      concept", he established the MEMO database, in which data on the acutely toxic
      human blood concentrations of drugs and chemicals were collated from the
      literature and from clinical studies. He also initiated another project,
      Evaluation-Guided Development of In Vitro Toxicity and Toxicokinetic Tests
      (EDIT). The ideas from the EDIT project, together with those from the MEIC
      project, became the basis for today's international EU projects, e.g. ACuteTox,
      Sens-it-iv and ReProTect. In this article, 10 years after the start of the BEMF,
      the scientific achievements of each of the award winners in the field of in vitro
      toxicology are presented, together with a brief synopsis of their careers.

PMID- 21942550
TI  - The latest statistics of scientific procedures on living animals reveal little
      three rs progress in great britain in 2010.
AB  - The 2010 Statistics of Scientific Procedures on Living Animals showed that the
      level of animal experimentation in Great Britain continues to rise, with just
      over 3.7 million procedures being conducted. This is almost exclusively due to
      the sustained increase in the breeding and utilisation of genetically-altered
      animals. Here, the general trends in the species used and the numbers and types
      of procedures are reviewed. In addition, the impact of the recent Government
      announcement to ban testing of household products on animals is discussed, along
      with the implications of the fish becoming the second most frequently used animal
      in scientific research. Finally, concerns about primate use, the REACH System,
      cosmetics testing and the new EU Directive on the protection of laboratory
      animals are explained.

PMID- 21942551
TI  - Biomedical research involving chimpanzees.

PMID- 21942552
TI  - A practical synthesis of zanamivir phosphonate congeners with potent anti
      influenza activity.
AB  - Two phosphonate compounds 1a (4-amino-1-phosphono-DANA) and 1b (phosphono
      zanamivir) are synthesized and shown more potent than zanamivir against the
      neuraminidases of avian and human influenza viruses, including the oseltamivir
      resistant strains. For the first time, the practical synthesis of these
      phosphonate compounds is realized by conversion of sialic acid to peracetylated
      phosphono-DANA diethyl ester (5) as a key intermediate in three steps by a novel
      approach. In comparison with zanamivir, the high affinity of 1a and 1b can be
      partly attributable to the strong electrostatic interactions of their phosphonate
      groups with the three arginine residues (Arg118, Arg292, and Arg371) in the
      active site of neuraminidases. These phosphonates are nontoxic to the human 293T
      cells; they protect cells from influenza virus infection with EC(50) values in
      low-nanomolar range, including the wild-type WSN (H1N1), the 2009 pandemic
      (H1N1), the oseltamivir-resistant H274Y (H1N1), RG14 (H5N1), and Udorn (H3N2)
      influenza strains.

PMID- 21942553
TI  - Amniotic fluid soluble Toll-like receptor 4 in pregnancies complicated by preterm
      prelabor rupture of the membranes.
AB  - OBJECTIVE: To determine amniotic fluid soluble Toll-like receptor 4 (sTLR4)
      levels in women with preterm prelabor rupture of the membranes according to the
      presence of microbial invasion of the amniotic cavity and histological
      chorioamnionitis and its relation to neonatal outcome. METHODS: One hundred two
      women with singleton pregnancies with a gestational age between 24 + 0 and 36 + 6
      weeks were included in a prospective cohort study. Amniocenteses were performed,
      and the concentrations of sTLR4 in the amniotic fluid were determined using
      sandwich enzyme-linked immunosorbent assay technique. RESULTS: Women with the
      presence of microbial invasion of the amniotic cavity had higher sTLR4 levels
      [median 54.2 ng/mL, interquartile range (IQR) 10.15-289.9] than those without
      this condition (median 18.1 ng/mL, IQR 8.1-29.9; p = 0.001). Women with the
      presence of histological chorioamnionitis had a higher sTLR4 level (median 28.0
      ng/mL, IQR 11.15-178.1) compared with women without histological chorioamnionitis
      (median 13.0 ng/mL, IQR 7.8-28.7; p = 0.003). A mixed linear model was used to
      adjust for confounders. The difference was found only between women with and
      without microbial invasion of the amniotic cavity in this model. CONCLUSIONS:
      Microbial invasion of the amniotic cavity was associated with higher amniotic
      fluid sTLR4 levels independent of confounders.

PMID- 21942554
TI  - Multifaceted roles of curcumin: two sides of a coin!
AB  - INTRODUCTION: Curcumin has been a front-line topic of mainstream scientific
      research for a variety of diseases from cancer to Alzheimer's to infectious
      diseases. Curcumin suppresses the type 1 immune response, which might lead to
      alleviation of type 1 immune response disorders. However, the inhibition of type
      1 immune response might invite infections with opportunistic pathogens.
      Considering its low bioavailability, several curcumin derivatives have been
      designed to improve its functionality. AREAS COVERED: This is a consolidated
      review which aims to compare and contrast diverse aspects of curcumin in variety
      of diseases. The intricate underlying mechanisms and the functional determinants
      of curcumin are discussed. EXPERT OPINION: Curcumin being considered as a spicy
      panacea, is not a remedy for all diseases. However, its ability to act
      differentially as an anti-oxidant or pro-oxidant akin to that of a double-edged
      sword/friend turning foe can be either beneficial or harmful for the host. It
      exhibits anti-oxidant properties at concentrations achievable in the body, making
      the host vulnerable to infections due to the suppression of innate immune
      responses. With the increase in knowledge of its functional groups, production of
      analogues of curcumin is underway to enhance its bioavailability and hence its
      therapeutic potency.

PMID- 21942555
TI  - The relationship between blushing propensity, social anxiety and facial blood
      flow during embarrassment.
AB  - To investigate blushing in relation to blushing propensity scores and core
      elements of social anxiety, facial blood flow was monitored in 86 normal
      volunteers during an embarrassing task (singing a children's song). Increases in
      facial blood flow were greater in women than men, as were scores on the Blushing
      Propensity and Fear of Negative Evaluation scales. In addition, high scores on
      the Blushing Propensity and Social Interaction Anxiety scales were associated
      with large increases in facial blood flow during singing. However, this appeared
      to be due primarily to social anxiety because the association between blushing
      propensity scores and changes in facial blood flow disappeared when social
      interaction anxiety scores were taken into account. These findings suggest that
      people generally base their beliefs about blushing on cues other than changes in
      facial blood flow. Social anxiety may augment increases in facial blood flow
      during embarrassment, independently of expected or perceived blushing.

PMID- 21942556
TI  - Lipoprotein-associated phospholipase A2 activity in patients with preserved left
      ventricular ejection fraction.
AB  - BACKGROUND: A significant proportion of heart failure (HF) patients have
      preserved ejection fraction (EF). Considering that inflammation and oxidative
      stress are involved in HF evolution, we investigated lipoprotein-associated
      phospholipase A2 (LpPLA2), an enzyme involved in these pathophysiologic processes
      in relation to EF. METHODS AND RESULTS: The study included 208 HF patients and 20
      healthy controls. HF patients with preserved EF (HFpEF) represented 42.31% of all
      HF patients. LpPLA2 activity was significantly increased in HF patients when
      compared with controls and was higher in HFpEF than in HF with reduced EF
      patients (HFrEF). The incidence of left ventricular hypertrophy was higher in
      HFpEF than in HFrEF (EF < 50). CONCLUSION: Confirming its role as a marker of
      vascular inflammation, LpPLA2 seems to be a biomarker constantly correlated with
      HF, regardless of etiology. Elevated plasma values of LpPLA2 in HFpEF are
      consistent with the exacerbated inflammatory status.

PMID- 21942557
TI  - Structural revision and total synthesis of caraphenol B and C.
AB  - Chemical syntheses of two stereochemically unique resveratrol dimers, caraphenols
      B and C, have shown that their structures are misassigned. Thoughts on their
      potential chemical etiology led to an alternate structural proposal that has been
      confirmed through synthesis, one indicating that the substituents on their
      respective indane systems exist in a relative trans,trans orientation rather than
      the originally postulated all-cis arrangement.

PMID- 21942563
TI  - Animal Verbal Fluency and Design Fluency in school-aged children: effects of age,
      sex, and mean level of parental education, and regression-based normative data.
AB  - The Animal Verbal Fluency (AVF) and Design Fluency (DF) structured and
      unstructured test versions were administered to N = 294 healthy native Dutch
      speaking children who were aged between 6.56 and 15.85 years. The AVF and DF
      structured test scores increased linearly as a function of age, whilst the
      relation between age and the DF unstructured test score was curvilinear (i.e.,
      the improvement in test scores was much more pronounced for younger children than
      for older children). A higher mean level of parental education was associated
      with significantly higher AVF and DF structured test scores. Sex was not
      associated with any of the outcomes. Demographically corrected norms for the AVF
      and DF tests were established, and an automatic scoring program was provided.

PMID- 21942564
TI  - Fabrication of 3D metal dot arrays by geometrically structured dynamic shadowing
      lithography.
AB  - Sphere lithography (SL), sometimes erroneously generalized as nanosphere
      lithography (NSL), stands out as a versatile technique capable of producing 2D
      periodic micro- and nanostructures with general materials applicability, flexible
      size and shape control, high throughput, and elegance of simplicity. Many of the
      fundamental aspects of the features produced by SL have been investigated in a
      systematic manner, including the optical, magnetic, electronic, and catalytic
      behaviors with emphasis toward applications in biosensing, ultrasensitive
      spectroscopy, and nanodevice fabrication. Previous work has primarily focused on
      two-dimensional patterning, however, with little attention paid to vertical
      growth of the SL features. In this work, the 3D structural evolution of metal dot
      arrays at two different length scales was demonstrated by SL-based geometrically
      structured dynamic shadowing lithography (GSDSL). An empirically derived model of
      structural growth is also developed to predict the shape and size of the features
      in this system.

PMID- 21942565
TI  - Insulating state and breakdown of Fermi liquid description in molecular-scale
      single-crystalline wires of gold.
AB  - Electrical transport measurements on ultrathin single-crystalline Au nanowires,
      synthesized via a wet chemical route, show an unexpected insulating behavior. The
      linear response electrical resistance exhibits a power-law dependence on
      temperature. In addition, the variation of current over a wide range of
      temperature and voltage obeys a universal scaling relation that provides
      compelling evidence for a non-Fermi liquid behavior. Our results demonstrate that
      the quantum ground state in ultrathin nanowires of simple metallic systems can be
      radically different from their bulk counterparts and can be described in terms of
      a Tomonaga-Luttinger liquid (TLL), in the presence of remarkably strong electron
      electron interactions.

PMID- 21942567
TI  - N,N'-Dithiobisphthalimide, a disulfide aromatic compound, is a potent spermicide
      agent in humans.
AB  - Several studies have shown that users of vaginal preparations containing
      nonoxynol-9 (N-9) are at a high risk for sexually transmitted diseases, including
      HIV. Therefore, there is a great interest in identifying compounds that can
      specifically inhibit sperm without damaging the vaginal lining, possess a
      powerful spermicide activity, and can be used in contraceptive vaginal
      preparations to replace N-9. In this work, we studied the spermostatic and/or
      spermicidal activity of five non-detergent, disulfide compounds on human sperm,
      HeLa cells, and Lactobacillus acidophilus. The motility and viability of human
      sperm in semen and culture medium was evaluated after treatment with different
      concentrations of the disulfide compounds (2.5 - 100 uM). In addition, we
      evaluated the cytotoxic effect on HeLa cells and L. acidophilus. We identified
      compound 101, N,N'-dithiobisphthalimide (No. CAS 7764-30-9), as the most
      effective molecule. It has a half maximal effective concentration (EC(50)) of 8
      uM and a minimum effective concentration (defined as the concentration that
      immobilizes 100 percent of the sperm in 20 sec) of 24 uM. At these
      concentrations, compound 101 does not affect the viability of the sperm, HeLa
      cells, or L. acidophilus. Our results indicate that dithiobisphthalimide has a
      potent spermostatic, irreversible effect with no toxic effects on HeLa cells and
      L. acidophilus.

PMID- 21942566
TI  - The alpha-amino group of the threonine substrate as the general base during tRNA
      aminoacylation: a new version of substrate-assisted catalysis predicted by hybrid
      DFT.
AB  - Density functional theory-based methods in combination with large chemical models
      have been used to investigate the mechanism of the second half-reaction catalyzed
      by Thr-tRNA synthetase: aminoacyl transfer from Thr-AMP onto the (A76)3'OH of the
      cognate tRNA. In particular, we have examined pathways in which an active site
      His309 residue is either protonated or neutral (i.e., potentially able to act as
      a base). In the protonated His309-assisted mechanism, the rate-limiting step is
      formation of the tetrahedral intermediate. The barrier for this step is 155.0 kJ
      mol(-1), and thus, such a pathway is concluded to not be enzymatically feasible.
      For the neutral His309-assisted mechanism, two models were used with the
      difference being whether Lys465 was included. For either model, the barrier of
      the rate-limiting step is below the upper thermodynamic enzymatic limit of ~125
      kJ mol(-1). Specifically, without Lys465, the rate-limiting barrier is 122.1 kJ
      mol(-1) and corresponds to a rotation about the tetrahedral intermediate C(carb)
      OH bond. For the model with Lys465, the rate-limiting barrier is slightly lower
      and corresponds to the formation of the tetrahedral intermediate. Importantly,
      for both "neutral His309" models, the neutral amino group of the threonyl
      substrate directly acts as the proton acceptor; in the formation of the
      tetrahedral intermediate, the (A76)3'OH proton is directly transferred onto the
      Thr-NH(2). Therefore, the overall mechanism follows a general substrate-assisted
      catalytic mechanism.

PMID- 21942568
TI  - Negative-ion electron capture dissociation: radical-driven fragmentation of
      charge-increased gaseous peptide anions.
AB  - The generation of gaseous polyanions with a Coulomb barrier has attracted
      attention as exemplified by previous studies of fullerene dianions. However, this
      phenomenon has not been reported for biological anions. By contrast, electron
      attachment to multiply charged peptide and protein cations has seen a surge of
      interest due to the high utility for tandem mass spectrometry (MS/MS). Electron
      capture dissociation (ECD) and electron transfer dissociation (ETD) involve
      radical-driven fragmentation of charge-reduced peptide/protein cations to yield N
      C(alpha) backbone bond cleavage, resulting in predictable c'/z(*)-type product
      ions without loss of labile post-translational modifications (PTMs). However,
      acidic peptides, e.g., with biologically important PTMs such as phosphorylation
      and sulfonation, are difficult to multiply charge in positive ion mode and show
      improved ionization in negative-ion mode. We found that peptide anions ([M -
      nH](n-), n >= 1) can capture electrons within a rather narrow energy range (~3.5
      6.5 eV), resulting in charge-increased radical intermediates that undergo
      dissociation analogous to that in ECD/ETD. Gas-phase zwitterionic structures
      appear to play an important role in this novel MS/MS technique, negative-ion
      electron capture dissociation (niECD).

PMID- 21942569
TI  - Black-capped chickadee (Poecile atricapillus) and human (Homo sapiens) chord
      discrimination.
AB  - Human music perception is related both to musical experience and the physical
      properties of sound. Examining the processing of music by nonhuman animals has
      been generally neglected. We tested both black-capped chickadees and humans in a
      chord discrimination task that replicates and extends prior research with
      pigeons. We found that chickadees and humans, in common with pigeons, showed
      similar patterns of discrimination across manipulations of the 3rd and 5th notes
      of the triadic chords. For all species (chickadee and humans here, pigeons
      previously), chords with half-step alterations in the 5th note were easier to
      discriminate than half-step manipulations of the 3rd note, which is likely due to
      the sensory consonance of these chords. There were differences among species in
      terms of the fine discrimination of the chords within this larger pattern of
      results. Further, the ability to relearn the chords when transposed to a new root
      differed across species. Our results provide new comparative data suggesting some
      similarities in chord perception that span a wide range of species, from pigeons
      (nonvocal learners) to songbirds and humans (vocal learners).

PMID- 21942570
TI  - The role of transmission biases in the cultural diffusion of irrelevant actions.
AB  - This study used a diffusion chain paradigm to explore the cultural transmission
      of causally irrelevant tool actions in chains of adult participants. Each chain
      witnessed an "expert" adult retrieve a reward from inside a puzzle box using a
      combination of causally relevant actions and causally irrelevant actions. Which
      of the actions were causally relevant was evident in two of the chains where a
      transparent box was used. In the other two chains, the causal effectiveness of
      the tool was hidden inside an opaque version of the box. Results indicated that
      fewer of the irrelevant actions performed by the expert model were reproduced in
      the transparent box chains, than the opaque box chains. However, irrelevant
      actions, although not in their original form, were evident within each chain
      suggesting that causally irrelevant tool actions can survive within groups of
      adults. The current article places these results, alongside those from earlier
      overimitation studies, within a framework of cultural evolution. The proposal
      here is that the social learning of irrelevant actions is heavily influenced by
      the interaction between various transmission biases, including frequency-based
      biases, model-based biases, and content-based biases. It is further proposed that
      the transmission bias witnessed may differ according to the interplay between
      characteristics of the model, characteristics of the observer, and the contents
      of the task.

PMID- 21942571
TI  - Template-directed synthesis of silica nanotubes for explosive detection.
AB  - Fluorescent porous organic-inorganic thin films are of interest of explosive
      detection because of their vapor phase fluorescence quenching property. In this
      work, we synthesized fluorescent silica nanotubes using a biomineralization
      process through self-assembled peptidic nanostructures. We designed and
      synthesized an amyloid-like peptide self-assembling into nanofibers to be used as
      a template for silica nanotube formation. The amine groups on the peptide
      nanofibrous system were used for nucleation of silica nanostructures. Silica
      nanotubes were used to prepare highly porous surfaces, and they were doped with a
      fluorescent dye by physical adsorption for explosive sensing. These porous
      surfaces exhibited fast, sensitive, and highly selective fluorescence quenching
      against nitro-explosive vapors. The materials developed in this work have vast
      potential in sensing applications due to enhanced surface area.

PMID- 21942572
TI  - Interconversion between [5]pseudorotaxane and [3]pseudorotaxane by
      pasting/detaching two axle molecules.
AB  - An acceptor-donor-acceptor-type linear molecule 1(2+) containing one electron
      rich naphthoxy (NP) unit and two monocharged viologen (MCV) units was
      synthesized. Through the noncovalent interaction of cucurbit[8]uril (CB[8]) with
      one NP and one MCV in 1(2+), we first obtained a [2]pseudorotaxane
      ([1(2+)]?CB[8]), and the excess CB[8] included simultaneously the two bare MCV
      units of two [2]pseudorotaxanes to form a [5]pseudorotaxane
      ([1(2+)](2)?[CB[8]](3)). Its transformation to [3]pseudorotaxane was achieved
      through detaching the two axle molecules in the presence of acid, and then the
      addition of base may result in a reversible switch between two different
      pseudorotaxanes. This novel methodology elongating reversibly linear molecules by
      noncovalent interactions will benefit the development of stimuli-responsive
      functional molecular devices.

PMID- 21942573
TI  - Spinal muscular atrophy patient detection and carrier screening using dried blood
      spots on filter paper.
AB  - AIM: Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular
      disorder. It is caused by mutations in the SMN1, and its clinical severity is
      modified by copy number variations of the SMN2. According to previous studies,
      deletion of SMN1 exon 7 is the most frequently observed in patients with SMA.
      Therefore, molecular analyses exploiting this genetic lesion could be beneficial
      in the diagnosis of SMA. Unfortunately, in many geographical regions, physicians
      do not have the latest molecular screening technologies at their immediate
      disposal. Thus, to overcome this issue, we developed an SMA-diagnosing system
      using dried blood spots (DBS) placed on filter paper to facilitate remote
      diagnosis. METHODS: In this study, we validate the applicability of DBS on
      Flinders Technology Associates (FTA) filter paper for detecting SMN1 exon 7
      deletions and copy number variations of SMN1 and SMN2. To detect exon 7 deletions
      in SMN1, polymerase chain reaction (PCR)-restriction fragment length polymorphism
      analysis was conducted by using DNA extracted from the DBS on FTA filter paper
      that had been stored at room temperature for a period of up to 4 years. To
      determine the copy numbers of SMN1 and SMN2, we carried out SYBR green-based real
      time PCR by using the same blood specimens. RESULTS: The results obtained from
      the DBS on FTA filter paper were in complete concordance with those analyses
      using fresh blood specimens. This indicates that DBS on filter papers is a
      reliable method for SMA patient detection and carrier screenings. CONCLUSION: The
      SMA-diagnosing system, combined with the mailing of DBS on filter paper, will be
      beneficial for patients suffering from neuromuscular disorders in areas with
      limited or no access to diagnostic facilities with molecular capabilities.

PMID- 21942575
TI  - Catalytic asymmetric Pictet-Spengler-type reaction for the synthesis of optically
      active indolo[3,4-cd][1]benzazepines.
AB  - A new strategy has been introduced to develop a catalytic asymmetric Pictet
      Spengler-type reaction by replacing the aldehyde with an imine. A range of 4-(2
      aminoaryl)indoles smoothly undergo the chiral phosphoric acid catalyzed
      asymmetric Pictet-Spengler-type reaction with imines at room temperature to give
      structurally diverse indolo[3,4-cd][1]benzazepines in good to excellent yields
      and ee.

PMID- 21942576
TI  - Serum kinetics of soluble triggering receptor expressed on myeloid cells-1
      differs in relation to the type of arthroplasty.
AB  - CONTEXT: Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1)
      participates in the inflammatory process. PURPOSE: To describe changes of sTREM-1
      in the serum after hemiarthroplasty (HA) and total hip arthroplasty (THA).
      METHODS: Serial blood samples were drawn from 122 patients with hip fracture.
      Interleukin-6 (IL-6), sTREM-1, and C-reactive protein (CRP) were measured.
      RESULTS: IL-6 and CRP were similarly increased after both HA and THA. sTREM-1 was
      increased early in HA and late after THA. The only parameter that was higher
      among patients who developed systemic inflammatory response syndrome was IL-6.
      CONCLUSIONS: Kinetics of sTREM-1 differs among patients undergoing HA of the hip
      and those undergoing THA.

PMID- 21942577
TI  - The half-life of cognitive-affective states during complex learning.
AB  - We investigated the temporal dynamics of students' cognitive-affective states
      (confusion, frustration, boredom, engagement/flow, delight, and surprise) during
      deep learning activities. After a learning session with an intelligent tutoring
      system with conversational dialogue, the cognitive-affective states of the
      learner were classified by the learner, a peer, and two trained judges at
      approximately 100 points in the tutorial session. Decay rates for the cognitive
      affective states were estimated by fitting exponential curves to time series of
      affect responses. The results partially confirmed predictions of goal-appraisal
      theories of emotion by supporting a tripartite classification of the states along
      a temporal dimension: persistent states (boredom, engagement/flow, and
      confusion), transitory states (delight and surprise), and an intermediate state
      (frustration). Patterns of decay rates were generally consistent across affect
      judges, except that a reversed actor-observer effect was discovered for
      engagement/flow and frustration. Correlations between decay rates of the
      cognitive-affective states and several learning measures confirmed the major
      predictions and uncovered some novel findings that have implications for theories
      of pedagogy that integrate cognition and affect during deep learning.

PMID- 21942578
TI  - Impact of a women's counselling programme on combined hormonal contraception in
      Portugal--the IMAGINE Study.
AB  - BACKGROUND: The aim of this health education project was to measure the impact of
      counselling about combined hormonal contraceptive (CHC) methods on the subsequent
      choice of method by Portuguese women. METHOD: This was a multi-centre study with
      a representative population, at the national and regional levels, of 2951
      Portuguese women>=16 years of age visiting the gynaecologist. Counselling on
      available CHC methods was provided using a single leaflet, and their CHC choice
      was assessed before and after counselling. RESULTS: A combined oral contraceptive
      (COC) was the method preferred by the majority of the women prior to counselling.
      After counselling, 35% of women who initially had chosen the pill, switched to
      either the vaginal ring or the transdermal patch, and the difference was
      statistically significant. Ease of use was the major reason for choosing the COC,
      while a lower probability of omission was the reason for choosing the vaginal
      ring and the patch. CONCLUSIONS: The implementation of a counselling programme
      significantly affected contraceptive choices leading in a number of cases to the
      selection of alternatives better suited to women's lifestyle. Age and educational
      level are socio-demographic factors which play an important role.

PMID- 21942580
TI  - The natural history of vesicoureteral reflux.
AB  - Vesicoureteral reflux (VUR) is the greatest and most recent challenge in
      pediatric nephrology, with explosive and relentless growth of knowledge. Many
      diagnostic and therapeutic indications must be revised with regards to up-to-date
      discoveries on the origin and evolution of congenital anomalies of kidneys and
      urinary tracts (CAKUT), because prompt diagnosis and aggressive intervention
      often seem to have only marginal influence on remote prognosis. Diagnostic
      strategies must tend to minimize the number of useless studies, preferring the
      ones that are less invasive and which expose to the smallest radiologic risk,
      reminding that the target is prevention of parenchymal damage, and not detecting
      VUR.

PMID- 21942581
TI  - Esophageal atresia: pre and post-operative management.
AB  - Esophageal atresia is a relatively common congenital malformation occurring in
      1:3000-4500 live births. Improvement in surgical, anesthetic and neonatal care
      has achieved a survival rate near 100% in infants weighing over 1500 g and having
      no major cardiac problem. To achieve these outcomes, as well as a good surgical
      technique, careful preoperative management (early diagnosis, investigation of
      associated anomalies, suction of the upper pouch, prevention and treatment of
      gastric and bowel distension) and accurate postoperative care (postoperative
      analgesia and ventilation, management of trans-anastomotic and chest tube,
      prevention, early recognition and treatment of complications) are mandatory.

PMID- 21942582
TI  - Vitamin D as a drug.
AB  - Vitamin D has an important role in bone-metabolism (and its deficiency can cause
      preterm osteopenia, craniotabe and rickets), but it has also non-calcitropic
      functions. In fact, vitamin D deficiency is correlated to chronic kidney disease,
      respiratory infections, type 1 diabetes, psoriasis, Crohn disease and neonatal
      hypocalcemia. Because of the vitamin D deficiency is a global problem, its role
      as a drug is fundamental for the human health in all ages.

PMID- 21942583
TI  - The sleep protection in the preterm infants.
AB  - The importance of sleep in the development is only now beginning to be
      understood: sleep and established sleep cycles have an important role in the
      normal neurosensory and cortex development. The biological basis of sleep
      organization has been highlighted by several studies however environmental
      differences can affect the sleep patterns in preterm infants in the NICU. Sleep
      disorders are related to several physiological conditions but it is important to
      know the relationship between sleep organization and neurocognitive and socio
      emotional outcomes. From the recent literature it is possible to find out
      potentially better practices that preserve and promote infant sleep in the NICU.

PMID- 21942584
TI  - Red blood cell transfusion in preterm infants: restrictive versus liberal policy.
AB  - Preterm neonates represent a category of patients with high transfusion needs.
      Ideally, red blood cells (RBC) transfusion should be tailored to the individual
      requirements of the single infant. However, despite the progress in neonatal
      transfusion medicine, many controversies still remain, and the decision on
      whether to transfuse or not is often made on empirical basis, with large
      variation in transfusion practices among neonatologists. Recently, a few clinical
      trials have been performed with the aim to compare the risk/benefit ratio of
      restrictive versus liberal transfusion criteria. Most of the studies failed to
      demonstrate significant differences in short-term outcomes, suggesting that the
      restrictive criteria may reduce the need for transfusion and the related side
      effects. Neurodevelopmental long-term outcome seemed more favorable in the
      liberal group at a first evaluation, especially for boys, and significantly
      better in the restrictive group at a later clinical investigation. Magnetic
      resonance imaging scans, performed at an average age of 12 years, showed that
      intracranial volume was substantially smaller in the liberal group compared with
      controls. When sex effects were evaluated, the girls in the liberal group had the
      most significant abnormalities. In conclusion, when preventive measures, as
      favoring cord clamping delay or cord milking, ensuring optimal nutrition, and
      minimizing phlebotomy losses, fail to avoid the need for transfusion, it is
      preferable to adopt restrictive criteria.

PMID- 21942585
TI  - Prevention of nosocomial infections and surveillance of emerging resistances in
      NICU.
AB  - Neonates hospitalized in NICU are at risk for healthcare associated infections
      because of their poor immune defenses, related to gestational age, colonization
      of mucous membranes and skin with nosocomial microorganisms, exposure to
      antibiotics, invasive procedures and frequent contacts with healthcare workers
      (HCWs). Healthcare associated infections are the major source of morbidity and
      mortality in NICU in the developed world. Most infections are caused by Gram
      positive organisms, fulminant sepsis are often associated to Gram-negative
      organisms, fungal sepsis occurs frequently in ELBW infants. Hand hygiene is the
      most important preventive procedure, nevertheless hand hygiene compliance among
      HCWs remains low. Continuous educational strategies can improve hand hygiene and
      contribute to reducing the incidence of neonatal infections. Other important
      prevention strategies include early enteral feeding with human milk, minimization
      and safety in the use of invasive devices, limiting unnecessary empiric
      broadspectrum antibiotics, eventual use of lactoferrin bifidobacteria and
      lactobacilli, prophylactic administration of fluconazole in VLBW. Emergence of
      multi drug resistant organisms (MDRO) is a worrying perspective. Methicillin
      resistant Staphylococcus aureus (MRSA) is an important healthcare-associated
      pathogen. Active surveillance culturing for MRSA carriers, in combination with
      contact precautions and decolonization in some hyperendemic settings, has been
      proved to reduce MRSA transmission and infection rates. Multidrug-resistant Gram
      negatives are frequently reported. Overuse of antimicrobial drugs and
      crosstransmission via caregiver hands, contaminated equipment or inanimate
      objects are the major drivers of selection and dissemination. Strategies to
      control outbreaks of MDRO colonization/infection in the NICU may include
      performing hand hygiene, cohorting and isolating patients, screening healthcare
      workers and performing admission and periodic surveillance cultures.

PMID- 21942586
TI  - Strategies to protect sleep.
AB  - Sleep is a very important element for the development of a premature newborn,
      because it helps in creating good clinical condition, good weight gain, mastering
      full oral feeding and improving parent-infant relationship as well. Moreover, the
      development of a correct sleeping-awaking pattern is a key factor for the
      development of the brain. To protect sleep is important to modify the
      environment, for example, reducing noise levels, creating period of semi darkness
      and protecting infant face from direct light. To obtain this, individualized
      care, based on infant behavioural cues, becomes fundamental, requiring a change
      in daily assistance that should become more relationship-oriented. It is also
      fundamental to foster the presence of parents because it helps the baby to feel
      more protected and allows him to relax.

PMID- 21942587
TI  - New therapeutic strategies for the treatment of patent ductus arteriosus.
AB  - In the present manuscript we will focus our attention on the drug choice and its
      dosage.some studies suggest that the failure of pharmacologic pda closure might
      be due to the inadequacy of the standard dose regimen, because of large
      interindividual pharmacokinetics and pharmacodynamic variations in premature
      infants. we discuss the possibility that the early treatment of pda with
      ibuprofen doses higher than those actually recommended might increase the closure
      rate in preterm infants.

PMID- 21942588
TI  - Fetal alcohol syndrome: new perspectives for an ancient and underestimated
      problem.
AB  - The knowledge of the dangers of alcohol consumption during pregnancy isn't indeed
      a new issue, but the recent evidences of ethyl-glucuronide and ethyl-sulfate in
      meconium as novel biomarkers of prenatal ethanol exposure open new perspectives
      for the early diagnosis of the alcohol-related birth defects. This is crucial for
      a better developmental outcome of the affected patients and for preventing
      additional cases in at risk families. The fetal alcohol syndrome is not a single
      entity but represents the most severe form of a spectrum of disorders, including
      distinctive craniofacial alterations, stunted growth and behavioral
      abnormalities, caused by complex gene-environment interactions. FAS must always
      be a diagnosis of exclusion and have to be differentiated from many conditions
      caused by other embryotoxin agents and genetic syndromes that share some
      phenotypic features. Even if the first trimester is considered the most
      vulnerable period, nowadays is known that a fetal damage might occur throughout
      all gestation. Since ethanol consumption is constantly increasing among young
      women, a substantial amount of work has to be made to implement the knowledge on
      alcohol fetal effects among women of childbearing age; moreover, awareness and
      training among professionals in the health care system might play a critical role
      in the early diagnosis of these serious conditions.

PMID- 21942589
TI  - Pharmacological research in neonatology.
AB  - In neonatology unit 40 to 80% of the drugs are used as off-label or unlicensed,
      particularly in Neonatal Intensive Care Unit (NICU), where it has been described
      that in a single patient up to 60 parenteral drugs can be administered. The
      course of a drug inside the organism can be defined in 4 different phases:
      absorption, distribution, metabolism, elimination; for each of these phases the
      newborn infant has different characteristics than child and adult. In the last
      years much more attention has been put in pharmacological research specific for
      the neonatal age and a good trial design should take into account the following
      points: (1) to define the pediatric disease in terms of natural history,
      prevalence, severity, treatment and impact of the new drug; (2) to avoid the "try
      and error" method based on the adult dose corrected for weight or age; (3) to use
      adapted methodologies (pharmacokinetics); (4) to avoid small clinical trials
      (limited number of patients), the use of Randomized Controlled Trials rather than
      observational studies; (5) to consider ethics providing clear information and
      reducing pain and stress to the baby and its family.

PMID- 21942590
TI  - Blood transfusion in infants: techniques and adverse events.
AB  - High risk infants, especially preterm ones, often require the administration of
      blood products. Specific guidelines and recommendations on this topic are
      continually issued and updated and their clinical application is strongly
      supported, in order to optimize the transfusion practice in neonatal and
      pediatric patients. Blood transfusion in infants has, in fact, specific
      indications, requires special considerations on technical procedures, and
      deserves particular awareness of possible errors and potential adverse reactions.

PMID- 21942591
TI  - Renal safety of Non Steroidal Anti Inflammatory Drugs (NSAIDs) in the
      pharmacologic treatment of patent ductus arteriosus.
AB  - Patent ductus arteriosus (PDA) often complicates the clinical course of neonates
      born prematurely and increases their short- and long-term morbidity. Treatment of
      PDA remains an ongoing debate among neonatologists for various issues such as the
      timing, the criteria and the methods for its closure. Non steroidal anti
      inflammatory drugs have been used as the standard pharmacological treatment for
      PDA. Indomethacin was the first one to be used. Its use though, waned due
      recognition of renal cerebral and gastrointestinal complications associated with
      the administration of this drug. Ibuprofen has emerged in clinical practice, as
      it has been reported to have lower nephrotoxicity. This review will examine
      existing data in the literature on the early- and long-term nephrotoxicity
      associated with the two drugs and will discuss present and future directions the
      management and prevention of this condition.

PMID- 21942592
TI  - Brain cooling and eligible newborns: should we extend the indications?
AB  - Therapeutic hypothermia (whole body or selective head cooling) is recognized as
      standard of care for brain injury control in term infants with perinatal hypoxic
      ischemic encephalopathy (HIE). Recent metanalyses and systematic reviews in human
      newborns have shown a reduction in mortality and long-term neurodevelopmental
      disability at 12-24 months of age, with more favourable effects in the less
      severe forms of HIE. HIE is most often noted in term newborns. Preterm infants
      can also suffer from HIE, but the clinical manifestations and pathology are
      different, involving subcortical gray matter injury in association with white
      matter damage. Several term and preterm animal experimental models showed that a
      reduction in brain temperature following a hypoxic-ischemic insult reduces energy
      expenditure and may reduce histological neuronal loss, but little is known on the
      safety of therapeutic hypothermia in preterm or very low birth weight (VLBW)
      infants. Hypothermia is one of the most promising future interventions for the
      treatment of acute ischemic stroke, and seems to improve survival and neurologic
      outcome after cardiac arrest in adults. Similarly, recent reviews have emphasized
      the possible role of therapeutic hypothermia after pediatric cardiac arrest, and
      a trial is ongoing to assess the benefits of induced hypothermia in pediatric
      traumatic brain injury. So far, there is a lack of data on other possible
      indications, i.e., neonates with stroke or after cardio-pulmonary resuscitation,
      and necrotizing enterocolitis. Carefully designed safety studies and large
      randomized trials for all the above conditions and especially for preterm infants
      should be planned.

PMID- 21942574
TI  - Sphingolipid and glycosphingolipid metabolic pathways in the era of
      sphingolipidomics.

PMID- 21942593
TI  - Near infrared spectroscopy in newborns with surgical disease.
AB  - NIRS has been used as a key device with the aim to evaluate the impact of surgery
      and anesthesia on cerebral and splanchnic oxygenation in neonatal population. The
      main applications has been in cardiac surgery, congenital diaphragmatic hernia
      and esophageal atresia. In this report we summarized the results published on the
      application of NIRS in neonatal surgery with particular respect to cerebral and
      splanchnic oxygenation, presenting also some future prospective.

PMID- 21942594
TI  - Mother infant relationship and bonding myths and facts.
AB  - Mother-infant relationship has always interested researchers worldwide. This
      paper reviews the development of the concept of mother infant bonding through the
      years.

PMID- 21942596
TI  - Physiological basis of food intolerance in VLBW.
AB  - To provide an overview on the role of gut immunity, nervous system and motility
      patterns in the development of feeding intolerance in newborns. Maturation of the
      GI is important not only for digestion and absorption, but for endocrine and
      exocrine function as well. There is little data available about the development
      of the motility function and of the mucosal barrier of the human gut, and in
      particular about the motility patterns and mucosal changes in newborns during
      early days of life. It is known that functional maturation of the
      gastrointestinal tract is quite different over time with respect to its
      anatomical development. Besides, the gastrointestinal tract through innate and
      specific immunologic factors, acts as a defense against ingested antigens. In
      addition to the mucous membrane integrity and digestion, numerous specific
      immunologic cells and mediators orchestrate such defensive mechanisms. In case of
      food antigens, the outcome is usually in favor of tolerance. Defects in that
      barrier, however, can lead to the development of aberrant immunologic responses,
      including hypersensitivity reactions. It is obvious that an appropriate feeding
      regimen during early infancy is in favor of food tolerance. However, in addition
      to genetic predisposition, development of tolerance is facilitated by an adequate
      gut barrier (immune or nonimmune), well-coordinated GI motility and nervous
      network, and appropriate food regimen.

PMID- 21942595
TI  - Weaning from mechanical ventilation.
AB  - Mechanical ventilation is often required by very preterm infants with respiratory
      failure, even if invasive respiratory support is related to lung injury and
      adverse neurologic outcomes. The exposure to mechanical ventilation should be
      therefore limited. Optimal extubation however remains challenging, as
      approximately 30% of intubated preterm infants fails attempted extubation due to
      poor respiratory drive, atelectasis, residual pulmonary function abnormalities or
      intercurrent illness. This review outlines the advantages of different weaning
      strategies that should be considered by neonatologists for current use to reduce
      unsuccessful extubation.

PMID- 21942597
TI  - Neonatal hyponatremia: differential diagnosis and treatment.
AB  - Hyponatremia is very frequent in neonates, especially in VLBW. Recent data have
      shown that hyponatremia is not so benign as previously believed,and several
      clinical studies have indicated that preterms with mild to moderate chronic
      hyponatremia may experience poor growth and development retardation. The aim of
      this review is to present how to differentiate hypovolemic, euvolemic and
      hypervolemic hypernatremias, suggesting algorithms for practical management.

PMID- 21942598
TI  - Why should we care about neonatal hyperbilirubinemia in 2011?
AB  - Recent research links serum bilirubin levels to a positive function in human
      health. Yet in the neonate hyperbilirubinemia is associated to damage to the CNS
      and beyond. This article summarizes the evidence for the double edged role of
      bilirubin with a focus on the neonatal period. Also we briefly describe some of
      the current shortcomings in the treatment of neonatal hyperbilirubinemia.

PMID- 21942599
TI  - Neonatal jaundice and human milk.
AB  - Breastfeeding is linked both to a greater jaundice frequency and intensity in the
      first postnatal days ("breastfeeding jaundice") and to visible jaundice
      persisting beyond the first two weeks of life ("breast milk jaundice"), but the
      appearance of skin jaundice is not a reason for interrupting breastfeeding which
      can and should continue without any interruption in most cases. There have been
      numerous contributions to the literature, which have rescaled the direct role of
      breast milk, both in early jaundice and in the more severe cases of late
      jaundice. In fact, the reviewed guidelines for detection and management of
      hyperbilirubinemia underline, how prevention of badly managed breastfeeding and
      early support for the couple mother-child are effective prevention measures
      against severe early-onset jaundice; furthermore, the breastfeeding interruption
      is no longer recommended as a diagnostic procedure to identify breast milk
      jaundice because of its low specificity and the risk to disregarding the
      detection of a potentially dangerous disease.

PMID- 21942600
TI  - Neonatal herpes simplex virus.
AB  - Herpes simplex virus is an important cause of neonatal infection, which can lead
      to death or long-term disabilities. Rarely in utero, the transmission frequently
      occurs during delivery. The disease may be disseminated, localized to the central
      nervous system, or involving skin, eye and/or mouth. Mortality rates markedly
      decreased with high-dose antiviral treatment. Diagnosis of neonatal infection is
      based on viral isolation from ulcerated vesicles or by scarifying mucocutaneous
      lesions. Recently polymerase chain reaction plays a central role for both viral
      detection (skin, mucosal, cerebrospinal fluid samples) and response to therapy.
      Vertical transmission may be decreased by prophylactic antiviral treatment.

PMID- 21942601
TI  - "Cohabitation" between NICU and PICU.
AB  - Neonatal and paediatric intensive care are usually provided in distinct units,
      characterized by highly specialized staffs dedicated either to critically ill
      newborns (NICUs) or to critically ill children (PICUs). However, such a model may
      be not suitable or even applicable to all medical organisations or to different
      local needs. Actually, in Europe there are several PICUs which routinely provide
      care also to neonatal patients, including extremely preterm infants. Conversely,
      there are many NICUs which occasionally, or systematically, admit also young
      infants and toddlers. Whilst many aspects of modern neonatal care do resemble
      those routinely used in the paediatric intensive care setting, several clinical
      issues are unique to each respective sector and cannot be easily translated to
      the other one. In order to guarantee the best quality of care, NICU doctors and
      nurses should acquire adequate competence and skills, by means of focused
      multidisciplinary training programmes, as well as extensive exposure to a wide
      paediatric case mix.

PMID- 21942602
TI  - Secular trend on congenital infections: insights from Campania region register
      for perinatal infection, southern Italy.
AB  - There is increasing pressure for prevention of vertically transmitted congenital
      infection and prenatal screening is recommended for main locally prevalent
      infections. Furthermore, systematic monitoring of their impact and effectiveness
      of practices is quite rare at National level. As a consequence of favorable
      conditions on Campania region of Southern Italy a monitoring system based on post
      delivery surveillance on congenital infection has been longtime piloted and
      seems ready to be exported at national level. Temporal trend analysis is showing
      change on focus and impact of prevalent congenital infection such as
      toxoplasmosis, rubella, syphilis and HIV. Moreover, the effect of recent massive
      immigration from Eastern EU and Africa requires further focus.

PMID- 21942603
TI  - Education in neonatology by simulation: between reality and declaration of
      intent.
AB  - An unexpected event is not rare in Neonatology and can be dramatic: the operators
      must act with the right skills and abilities in the shortest time. Often it is a
      team effort and each member must be trained adequately. According to the "Swiss
      cheese" model by J. Reason, an accident is never the consequence of a single
      error, but the very final result of a chain of misunderstandings, irregularities
      or negligence (cheese holes): several holes allow the final medical error.
      Therefore, we should avoid those holes in our work. The clinical risk is always
      around the corner. The legal issues are becoming more and more relevant and lead
      to a defensive medicine, which is definitely not the best practice. For this
      reason, raising the safety standards is mandatory. With this purpose, after a
      decade of experience in "traditional" training courses, we started testing a new
      strategy of continuous education in Neonatology by means of highfidelity
      simulation. Since 2008, we have arranged and managed a Center for Neonatal
      Simulation and Advanced Training in the Neonatology Unit of the University
      Hospital of Pisa. We have already delivered courses to pediatricians,
      neonatologists, anesthesiologists, gynecologists, emergency doctors, midwives and
      nurses, using an advanced Laerdal SimNewB simulator to teach diagnostic and
      therapeutic skills or communication strategies. The model has been proposed to
      the Italian Society of Neonatology and it has been decided to create a Task Force
      to discuss our model and encourage to use it in other Italian areas.

PMID- 21942604
TI  - Off-label drugs prescription in neonatology: a physician's duty or a medical
      hazardous attitude?
AB  - The off-label and unlicensed use of drugs in neonatology is a widespread reality
      in all the NICUs. Several explanations may be given to justify the extension of
      this phenomenon and, among them, the lack of ad hoc clinical trials in neonatal
      subpopulation and the freedom to cure worldwide recognized to relatives and
      physicians. It is well known that adverse effects are more frequent, more serious
      and more underreported when medicines are used unauthorized or off-label, being
      physicians in theory responsible for the newborn physical damage. To avoid this
      responsibility, we believe that a shared legal framework may be helpful where the
      informative process on risks/benefits ratio for the newborn has a pivotal role.
      The National and International Scientific Societies should promote a common
      guidelines also for the informations on drug effects to be supplied to relatives.
      But at the same time EMA has to implement its strong policy towards the mandatory
      request on trials, for every new drug, on specific neonatal and pediatric
      subpopulations.

PMID- 21942605
TI  - Information systems in neonatology and health planning.
AB  - Improving the well-being of infants and children is an important public health
      goal. To reach this objective public health authorities need in-depth knowledge
      of perinatal statistics as well as the organization of perinatal care. These data
      must be based on the use of reliable information describing both individual and
      organizational factors and short and long term outcomes. Several perinatal
      information sources are available in Italy for analyses aimed at producing
      evidence for health planning purposes: the National birth registry, Infant
      mortality registry and Neonatal networks. We describe their structure and
      summarize some evidence derived from the experiences conducted in the Lazio
      region.

PMID- 21942606
TI  - Psychological aspects when counseling families who have children with cochlear
      implants.
AB  - The report begins with the latest debate on Cochlear Implants (CI) - the role
      they play during the development of a deaf child, analyzing the psychological
      aspects which characterize the experiences of families of children who do get
      implanted, starting from the detection of deafness until after implantation. The
      aim is to demonstrate how in these experiences and during all developmental
      phases the significant role the psychologist plays and how important timely
      intervention of specific programs is for both child and parents. Numerous studies
      have demonstrated that CI offers advantages in terms of recuperating capacity to
      hear and the development of spoken language. Recent studies focusing on
      psychological aspects have shifted the attention to the positive results of CI in
      comparison to the social environment in addition to family traits such as the
      parental reaction to the diagnosis of their child's deafness, mental coping
      strategies and the subsequent behaviors they adopt. In 90% of these cases, the
      parents are hearing and often have no experience in regards to deafness, and this
      is why when they find out that their child is deaf, their reaction is similar to
      that of bereavement. Consequently, prior to implantation it is necessary that a
      psychologist makes an accurate assessment in order to be able to intervene in
      situations where there is parental stress and help them cope by implementing a
      copying paradigm. The reaction to child deafness and the strategies of copying
      that they have acquired influence the family's expectations in respects to the
      CI, and in turn this influences the outcome after implantation. During the
      assessment, an important aspect for the psychologist is evaluating the motivation
      towards the rehabilitative program and the strong interaction between the parents
      and the child - both of these elements are closely connected to a positive
      outcome of the CI. During the post implant period, recent studies have shown an
      improvement of parental behavior as well as the development of the child in the
      domains of shared attention, problem solving, symbolic play and social
      functioning. In addition, during this stage the relationships between parents and
      children are more effective, and all parental figures are positively motivated
      towards appropriate behaviors. Hence the effects of CI are no longer limited to
      the implanted child, but now entail the entire family. In fact, the parents judge
      the quality of their lives on the basis of how successful they perceive the
      results obtained by having their child undergo a CI. Consequently, they regulate
      their behavior and attitudes influencing the child's development. Parents
      themselves maintain that specialized psychological support is fundamental during
      all stages connected to CI and more generally to the overall development of their
      child.

PMID- 21942607
TI  - Postnatal management of newborn with antenatal detected urinary tract
      abnormalities.
AB  - The goals of postnatal management of congenital anomalies of the kidneys and the
      urinary tracts are two: The first to distinguish between patients (the minority)
      who are at risk for renal parenchyma damage, from neonates (the majority) who
      have not consequences to renal functionality; the second to avoid for healthy
      infant strenuous follow-up, painful diagnostic procedures, and unnecessary
      anxiety for their parents.

PMID- 21942608
TI  - How to decrease the number of caesarean sections in Italy.
AB  - The Director of the Obstetrics e Gynaecology Department of "San Leonardo" at
      Castellammare di Stabia (Naples) in the 2004 started a project focused on strong
      decreasing of the caesarean sections. This project exploited the methodologies of
      quality management used in Industrial and Services Industries and it succeeded in
      reducing the weight of caesarean sections from 52,7% to 17,5% of the total birth
      within 5 years.

PMID- 21942609
TI  - The development of language in babies and the role of the family.
AB  - Nowadays for deaf children there are many new opportunities that provide enhanced
      ways of hearing stimulation.These concerns may result as much more significant as
      the family is engaged in the stimulation program. An NHS program in Campania was
      launched in 2005. According to these concerns, the family plays a central role
      both in the diagnostic and the therapeutic intervention of the impaired children.
      As paradigm of the important role of the family in the rehab project is a
      comparison between two kids in charge by our team. The outcomes are better in
      children who received stimulation by the family.

PMID- 21942610
TI  - Transport as a system: reorganization of perinatal assistance in Northern
      Lombardy.
AB  - The organization of perinatal care has been a pivotal mean for improvement in
      neonatal survivals. Despite the excellent standard of assistance in Lombardy,
      Obstetrics and Neonatal Units of MBBM Foundation-Monza, Manzoni Hospital-Lecco
      and Niguarda Hospital-Milan put forward a pilot project proposing reorganization
      of perinatal care in the northern part of Lombardy. The main goals of the project
      are implementation of maternal transport system and use of neonatal back
      transport as a system to increase the availability of intensive care beds. The
      project's fundamental steps and critical points will be discussed.

PMID- 21942611
TI  - Clinical use of fresh-frozen plasma and cryoprecipitate in neonatal intensive
      care unit.
AB  - Evidence-based indications for the use of plasma products in neonatal medicine
      are limited to few conditions. In the setting of inherited disorders of
      hemostasis, fresh frozen plasma (FFP) and cryoprecipitate should be used as
      replacement therapy only if the specific factor concentrate is not available. FFP
      is indicated to treat disseminated intravascular coagulation (DIC), liver
      failure, vitamin K-dependent bleeding and to reconstitute whole blood for
      exchange transfusion. Despite the lack of evidence, the use of cryoprecipitate to
      treat neonates with acquired hypofibrinogenemia during DIC or liver failure is
      now considered standard therapy.

PMID- 21942612
TI  - First year follow-up of extremely low birth weight premature sextuplets: case
      report.
AB  - High order gestation rates have increased in many western countries in the last
      decades, which is mostly attributable to a contemporaneous increase in maternal
      age and infertility treatment. Multiple births have been associated with
      increased maternal and foetal morbidity and mortality during pregnancy and
      delivery, including the higher risk for spontaneous abortion, preeclampsia,
      hydramnios, and maternal haemorrhage. A higher frequency of preterm infants and
      low birth weight infants have also been reported, as well as a higher rate of
      malformations, abnormal growth, and trauma at delivery, than in singleton
      pregnancies. We describe herein the case of six ELBW newborns delivered at 27
      weeks and their first year follow-up. All the sextuplets survived and did not
      have extra uterine growth retardation (EUGR) when discharged from hospital. A
      developmental delay was detected in five infants at 12 months corrected age (CA),
      but none of them showed cerebral palsy or severe neurosensorial disabilities.

PMID- 21942613
TI  - Communication with parents in neonatal intensive care.
AB  - The psycho-relational problems in Neonatal Intensive Care Units (NICU) are
      complex and multifaceted and have only recently been properly addressed. Some
      specific factors make communication in NICU particularly problematic; the baby's
      clinical condition, the emotional and working conditions of the medical staff,
      the emotional state of the parents and the setting of the NICU and the
      interaction of multiple professional figures with the parents. The purpose of
      communication in NICUs is not only to inform parents of their child's clinical
      condition; the medical and nursing staff must also educate and guide parents so
      that they can actively participate in caring for their child and become true
      "partners" with the medical team in the decision-making process. Furthermore, the
      staff must also use their communication skills to understand and contain the
      anxieties and emotions of parents, supporting and comforting them through the
      most critical moments of their child's illness and possibly even bereavement.
      Given the number and complexity of the interpersonal exchanges that take place in
      the NICU, the risk of misunderstanding, misinterpretation and conflict is high.
      One could say that the interpersonal aspect is an area where the risk of
      iatrogenesis is elevated. It is recognized that poor staff-family interactions
      not only reflect negatively on the baby's care and are a source of distress and
      discontent for the parents, but are also a major cause of medico-legal litigation
      and increase the incidence of "burnout". Therefore, specific training of the
      staff in communication is essential if the optimal results, obtained through
      modern technology, are not to be invalidated.

PMID- 21942614
TI  - A prospective, randomized, double blind study comparing lutein to placebo for
      reducing occurrence and severity of retinopathy of prematurity.
AB  - Lutein has been shown to have antioxidant functions in newborns and with
      zeaxantin selectively taken up into the macula of the eye. We hypothesize that
      lutein administration may contribute to reducing the incidence of Retinopathy of
      Prematurity (ROP). This was a single center, double-blind randomized controlled
      study. Preterm infants with gestational age (GA) <= 32 weeks able to tolerate
      minimal enteral feeding before the seventh day of life (DOL) were enrolled;
      lutein and zeaxantin plasma concentrations and ROP occurrence and severity were
      evaluated. Sixty-three newborns were enrolled, 31 in the lutein group and 32 in
      the placebo group (one died before ROP assessment). The mean GA was 29.9 (+/-
      1.9) weeks and the mean birth weight was 1331 (+/- 415) grams. There were no
      differences in the incidence of ROP at any stage between groups. Oxidative injury
      is probably an additional mechanism of damage of the developing retinal vessels,
      and it probably plays only a minor role in the pathogenesis of ROP.
      Supplementation with antioxidant substances might have beneficial effects
      noticeable only on larger samples of high risk neonates or at very high dosage.
      Further investigations would be needed to evaluate whether lutein supplementation
      can influence functional rather than anatomical outcomes in preterm infants.

PMID- 21942615
TI  - A sensitive period for cochlear implantation in deaf children.
AB  - The absence of hearing, as in congenital deafness, affects normal development of
      the auditory brain resulting in deficits in spoken language. Cochlear implants
      provide direct stimulation to the central auditory nervous system of hearing
      impaired children allowing cortical development to progress. However,
      implantation needs to take place within a brief window in early childhood for it
      to be maximally effective to allow children to acquire speech and oral language.
      In this review, we describe age cut-offs for a sensitive period for central
      auditory development in children who receive cochlear implants. We review
      consequences for cortical re-organization and cortical de-coupling when children
      receive cochlear implants after the end of the sensitive period.

PMID- 21942616
TI  - Bilirubin-induced neurological damage.
AB  - The incidence of the neurological damage of due to severe neonatal jaundice is
      increasing mainly due to early discharge from the hospital. However the molecular
      mechanisms at the basis of the neurological damage are still largely unknown. We
      here summarize what is known and what is not yet known on how bilirubin may cause
      cellular damage to selective regions of the brain. This may hopefully help to
      develop diagnostic and therapeutic strategies for a more effective handling of
      this invalidating condition.

PMID- 21942617
TI  - The electronic medical record: pros and cons.
AB  - The design of electronic medical record (EMR) software has a strong impact on
      user acceptance. To keep up with the growing complexity of activities performed
      today in Neonatal Intensive Care Units a well-designed EMR must provide an
      overall vision of all up-to-date information concerning the patient, both machine
      generated and clinical diagnostics, and be equipped with and computerized
      physician order entry (CPOE) system. The diffusion of new technological
      innovations in critical care environments can have unintended consequences,
      including changes in workflow, staff roles, and patient outcomes. We rely on the
      pros and cons of a 10-year successful implementation of an electronic medical
      record in a third level neonatal care unit, initially dedicated exclusively to
      neonatal intensive care, then extended to intermediate care and finally reaching
      the nursery.

PMID- 21942619
TI  - Direct observation of electron confinement in epitaxial graphene nanoislands.
AB  - One leading question for the application of graphene in nanoelectronics is how
      electronic properties depend on the size at the nanoscale. Direct observation of
      the quantized electronic states is central to conveying the relationship between
      electronic structures and local geometry. Scanning tunneling spectroscopy was
      used to measure differential conductance dI/dV patterns of nanometer-size
      graphene islands on an Ir(111) surface. Energy-resolved dI/dV maps clearly show a
      spatial modulation, indicating a modulated local density of states due to quantum
      confinement, which is unaffected by the edge configuration. We establish the
      energy dispersion relation with the quantized electron wave vector obtained from
      a Fourier analysis of dI/dV maps. The nanoislands preserve the Dirac Fermion
      properties with a reduced Fermi velocity.

PMID- 21942620
TI  - Less mammographic density after nasal versus oral administration of
      postmenopausal hormone therapy.
AB  - OBJECTIVE: Nasal administration gives a more acute but shorter rise in serum
      hormone levels than oral administration and may therefore have less effect on the
      fibroglandular tissue in the breasts. We studied the change in mammographic
      breast density after nasal vs. oral administration of postmenopausal hormone
      therapy (PHT). METHODS: We studied participants in a randomized, controlled trial
      on the impact of nasal vs. oral administration of PHT (combined 17beta-estradiol
      plus norethisterone) for 1 year. Two radiologists classified mammographic density
      at baseline and after 1 year into four categories. Also, the percentage density
      was calculated by a computer-based method. The main outcome measure was the
      difference in the proportion of women with an increase in mammographic density
      category after 1 year between the nasal and oral groups. Also, the change in the
      percentage density was calculated. RESULTS: The study group comprised 112 healthy
      postmenopausal women (mean age 56 years), of whom 53 received oral and 59
      intranasal PHT. An increase in mammographic density category after 1 year was
      seen in 20% of the women in the nasal group and in 34% of the oral group. This
      resulted in a non-significant difference in the proportion of women in whom
      mammographic breast density had increased by 214% (95% confidence interval (CI)
      230% to 2.7%). The mean change in percentage density was 21.2% in the nasal group
      and + 1.2% in the oral group, yielding a 22.4% differential effect (95% CI 27.3%
      to 2.5%). CONCLUSIONS: One year of nasal PHT gave a smaller, although not
      statistically significant, increase in mammographic density than oral PHT.
      Remaining issues are the relation between the route of administration of PHT and
      breast complaints and breast cancer risk.

PMID- 21942621
TI  - Dynamics in the active site of beta-secretase: a network analysis of atomistic
      simulations.
AB  - The aspartic protease beta-secretase (BACE) catalyzes the hydrolysis of the
      amyloid precursor protein (APP) which leads to amyloid-beta aggregation and,
      ultimately, the perilous Alzheimer's disease. The conformational dynamics and
      free energy surfaces of BACE at three steps of the catalytic cycle are studied
      here by explicit solvent molecular dynamics simulations (multiple runs for a
      total of 2.2 MUs). The overall plasticity of BACE is essentially identical for
      the three states of the substrate: the octapeptide reactant, gem-diol
      intermediate, and cleavage products. In contrast, the network of hydrogen bonds
      in the active site is more stable in the complex of BACE with the gem-diol
      intermediate than the other two states of the substrate. The spontaneous release
      of the C-terminal (P1'-P4') fragment of the product follows a single-exponential
      time dependence with a time constant of 50 ns and does not require the opening of
      the flap. The fast dissociation of the C-terminal fragment is consistent with the
      transmembrane location and orientation of APP and its further processing by gamma
      secretase. On the other hand, the N-terminal (P4-P1) fragment of the product does
      not exit the BACE active site within the simulation time scale of 80 ns. A
      unified network analysis of the complexes of BACE with the three states of the
      substrate provides an estimation of the activation free energy associated with
      the structural rearrangements that involve only noncovalent interactions. The
      estimated rearrangement barriers are not negligible (up to 3 kcal/mol) but are
      significantly smaller than the barrier of the peptide bond hydrolysis reaction.

PMID- 21942622
TI  - Species-specific myoglobin oxidation.
AB  - The effect of the lipid oxidation product, 4-hydroxy-2-nonenal (HNE), on
      oxidation of oxymyoglobin (OxyMb) from seven different meat-producing species was
      investigated. Relative to controls, HNE increased OxyMb oxidation within all
      species (p < 0.05) at both 25 and 4  degrees C, pH 5.6. The relative effect of
      HNE was greater for myoglobins (Mbs) that contained 12 +/- 1 histidine (His)
      residues than for those that contained 9 His residues (p < 0.05); HNE efficacy in
      all species except chicken and turkey decreased with time. Mono-HNE adducts were
      detected in all species except chicken and turkey. In general, HNE alkylation
      increased the Mbs' ability to accelerate lipid oxidation in a microsome model.
      However, neither an HNE nor a Mb species dependent effect was observed. Results
      suggested that microsome model system associated lipid oxidation overshadowed HNE
      and species effects on OxyMb oxidation observed in lipid-free systems.

PMID- 21942623
TI  - Micellar transitions in solvent-annealed thin films of an amphiphilic block
      copolymer controlled with tunable surface fields.
AB  - We investigated the response of symmetric poly(styrene-block-4vinylpyridine) P(S
      b-4VP) diblock copolymer micelles to surface fields of variable strength at free
      surfaces and substrate interfaces when the micelles as spun were subjected to
      solvent annealing. Free surface interactions were controlled with solvent
      annealing in solvents of varied selectivity. On exposure to vapors of a solvent
      strongly selective for PS, the micelles retained their spherical shape but grew
      into cylindrical micelles or lamellar nanostructures via fusion on exposure to
      slightly selective or neutral solvent vapors. Giant 2D disks that completely
      wetted PS-grafted substrates resulted when spherical micelles were exposed to
      vapors of a highly selective solvent for P4VP. The interfacial interactions were
      controlled through subjecting them to UV/ozone (UVO) substrates initially coated
      with an end-grafted layer of short PS chains, with which the grafted PS chains
      became oxidized, degraded, or totally removed through UVO treatment for a
      controlled duration. When thin films were annealed in vapors of THF, the
      structural transition from spherical to cylindrical micelles depended on the
      interfacial field. On applying selective UVO exposure of optimal duration, we
      fabricated a substrate with two interfacial chemistries that promoted varied
      micellar species (spherical and cylindrical micelles) with a sharp boundary
      developed within thin films through solvent annealing for a controlled duration.

PMID- 21942624
TI  - Temperature effects on enzyme activity of chicken liver esterase used in
      calorimetric biosensor.
AB  - The temperature effects on enzyme activity at the conditions with and without
      inhibition, operation, and storage were investigated for free esterase and
      immobilized chicken liver esterase with three methods (adsorption, adsorption
      microcapsule, and adsorption-crosslinking) used in a calorimetric biosensor. The
      results indicated that the temperature had significant effects on the enzyme
      activity by means of catalytic reaction, irreversible denaturation, mass
      transfer, and structure deformation of resin. Among all the esterase, the
      adsorption-crosslinking immobilized esterase had the best performances of enzyme
      activity retention ratio (EARR), above 96% in operation and 90% in storage on
      condition of maintaining its response to dichlorvos.

PMID- 21942625
TI  - IR spectra of C2H5(+)-N2 isomers: evidence for dative chemical bonding in the
      isolated ethanediazonium ion.
AB  - The potential energy surface (PES) of C(2)H(5)(+)-N(2) is characterized in detail
      by infrared photodissociation (IRPD) spectroscopy of mass-selected ions in a
      quadrupole tandem mass spectrometer and ab initio calculations at the MP2/6
      311G(2df,2pd) level. The PES features three nonequivalent minima. Two local
      minima, 1-N(2)(H) and 1-N(2)(C), are adduct complexes with binding energies of
      D(0) = 18 and 12 kJ/mol, in which the N(2) ligand is weakly bonded by
      electrostatic forces to either the acidic proton or the electrophilic carbon atom
      of the nonclassical C(2)H(5)(+) ion (1), respectively. The global minimum 3 is
      the ethanediazonium ion, featuring a weak dative bond of D(0) = 38 kJ/mol. This
      interaction strength is sufficient to switch the C(2)H(5)(+) structure from
      nonclassical to classical. The 1-N(2)(C) isomer corresponds to the entrance
      channel complex for addition of N(2) to 1 yielding the product 3. This reaction
      involves a small barrier of 7 kJ/mol as a result of the rearrangement of the
      C(2)H(5)(+) ion. The partly rotationally resolved IRPD spectrum of C(2)H(5)(+)
      N(2) recorded in the C-H stretch range is dominated by four bands assigned to 3
      and one weak transition attributed to 1-N(2)(H). The abundance ratio of 1-N(2)(H)
      and 3 estimated from the IRPD spectrum as ~1% is consistent with the calculated
      free energy difference of 12 kJ/mol. As the ethanediazonium ion escaped previous
      mass spectrometric detection, the currently accepted value for the ethyl cation
      affinity of N(2) is revised from -DeltaH(0) = 15.5 +/- 1.5 to ~42 kJ/mol. The
      first experimental identification and characterization of 3 provides a sensitive
      probe of the electrophilic character and fluxionality of the ethyl cation.
      Comparison of 3 with related alkanediazonium ions reveals the drastic effect of
      the size of the alkyl chain on their chemical reactivity, which is relevant in
      the context of hydrocarbon plasma chemistry of planetary atmospheres and the
      interstellar medium, as well as alkylation reactions of (bio)organic molecules
      (e.g., carcinogenesis and mutagenesis of DNA material).

PMID- 21942626
TI  - Nanostructured titanium/diamond-like carbon multilayer films: deposition,
      characterization, and applications.
AB  - Titanium/diamond-like carbon multilayer (TDML) films were deposited using a
      hybrid system combining radio frequency (RF)-sputtering and RF-plasma enhanced
      chemical vapor deposition (PECVD) techniques under a varied number of Ti/diamond
      like carbon (DLC) bilayers from 1 to 4, at high base pressure of 1 * 10(-3) Torr.
      The multilayer approach was used to create unique structures such as nanospheres
      and nanorods in TDML films, which is confirmed by scanning electron microscopy
      (SEM) analysis and explained by a hypothetical model. Surface composition was
      evaluated by X-ray photoelectron spectroscopy (XPS), whereas energy dispersive X
      ray analysis (EDAX) and time-of-flight secondary ion mass spectrometer (ToF-SIMS)
      measurements were performed to investigate the bulk composition. X-ray
      diffraction (XRD) was used to evaluate the phase and crystallinity of the
      deposited TDML films. Residual stress in these films was found to be
      significantly low. These TDML films were found to have excellent nanomechanical
      properties with maximum hardness of 41.2 GPa. In addition, various nanomechanical
      parameters were calculated and correlated with each other. Owing to metallic
      interfacial layer of Ti in multilayer films, the optical properties, electrical
      properties, and photoluminescence were improved significantly. Due to versatile
      nanomechanical properties and biocompatibility of DLC and DLC based films, these
      TDML films may also find applications in biomedical science.

PMID- 21942627
TI  - Therapeutic potential for HDAC inhibitors in the heart.
AB  - Reversible protein acetylation provides a central mechanism for controlling gene
      expression and cellular signaling events. Two pharmacological inhibitors of
      protein deacetylation are currently approved for the treatment of human cancer,
      and numerous follow-on compounds are in clinical development for oncology and non
      oncology indications. The inhibitors target members of a family of enzymes known
      as histone deacetylases (HDACs). Surprisingly, HDAC inhibitors have also been
      shown to be efficacious in preclinical models of heart failure. This review
      highlights roles of HDACs in the heart and the therapeutic potential of HDAC
      inhibitors for the treatment of heart failure.

PMID- 21942628
TI  - Adherence to medications: insights arising from studies on the unreliable link
      between prescribed and actual drug dosing histories.
AB  - Satisfactory adherence to aptly prescribed medications is essential for good
      outcomes of patient care and reliable evaluation of competing modes of drug
      treatment. The measure of satisfactory adherence is a dosing history that
      includes timely initiation of dosing plus punctual and persistent execution of
      the dosing regimen throughout the specified duration of treatment. Standardized
      terminology for initiation, execution, and persistence of drug dosing is
      essential for clarity of communication and scientific progress. Electronic
      methods for compiling drug dosing histories are now the recognized standard for
      quantifying adherence, the parameters of which support model-based, continuous
      projections of drug actions and concentrations in plasma that are confirmable by
      intermittent, direct measurements at single time points. The frequency of
      inadequate adherence is usually underestimated by pre-electronic methods and thus
      is clinically unrecognized as a frequent cause of failed treatment or
      underestimated effectiveness. Intermittent lapses in dosing are potential sources
      of toxicity through hazardous rebound effects or recurrent first-dose effects.

PMID- 21942630
TI  - Drug transporters in drug efficacy and toxicity.
AB  - Drug transporters are now widely acknowledged as important determinants governing
      drug absorption, excretion, and, in many cases, extent of drug entry into target
      organs. There is also a greater appreciation that altered drug transporter
      function, whether due to genetic polymorphisms, drug-drug interactions, or
      environmental factors such as dietary constituents, can result in unexpected
      toxicity. Such effects are in part due to the interplay between various uptake
      and efflux transporters with overlapping functional capabilities that can
      manifest as marked interindividual variability in drug disposition in vivo. Here
      we review transporters of the solute carrier (SLC) and ATP-binding cassette (ABC)
      superfamilies considered to be of major importance in drug therapy and outline
      how understanding the expression, function, and genetic variation in such drug
      transporters will result in better strategies for optimal drug design and tissue
      targeting as well as reduce the risk for drug-drug interactions and adverse drug
      responses.

PMID- 21942629
TI  - Molecular mechanism of beta-arrestin-biased agonism at seven-transmembrane
      receptors.
AB  - The concept of biased agonism has recently come to the fore with the realization
      that seven-transmembrane receptors (7TMRs, also known as G protein-coupled
      receptors, or GPCRs) activate complex signaling networks and can adopt multiple
      active conformations upon agonist binding. As a consequence, the "efficacy" of
      receptors, which was classically considered linear, is now recognized as
      pluridimensional. Biased agonists selectively stabilize only a subset of receptor
      conformations induced by the natural "unbiased" ligand, thus preferentially
      activating certain signaling mechanisms. Such agonists thus reveal the intriguing
      possibility that one can direct cellular signaling with unprecedented precision
      and specificity and support the notion that biased agonists may identify new
      classes of therapeutic agents that have fewer side effects. This review focuses
      on one particular class of biased ligands that has the ability to alter the
      balance between G protein-dependent and beta-arrestin-dependent signal
      transduction.

PMID- 21942631
TI  - The chemical biology of naphthoquinones and its environmental implications.
AB  - Quinones are a group of highly reactive organic chemical species that interact
      with biological systems to promote inflammatory, anti-inflammatory, and
      anticancer actions and to induce toxicities. This review describes the chemistry,
      biochemistry, and cellular effects of 1,2- and 1,4-naphthoquinones and their
      derivatives. The naphthoquinones are of particular interest because of their
      prevalence as natural products and as environmental chemicals, present in the
      atmosphere as products of fuel and tobacco combustion. 1,2- and 1,4
      naphthoquinones are also toxic metabolites of naphthalene, the major polynuclear
      aromatic hydrocarbon present in ambient air. Quinones exert their actions through
      two reactions: as prooxidants, reducing oxygen to reactive oxygen species; and as
      electrophiles, forming covalent bonds with tissue nucleophiles. The targets for
      these reactions include regulatory proteins such as protein tyrosine
      phosphatases; Kelch-like ECH-associated protein 1, the regulatory protein for NF
      E2-related factor 2; and the glycolysis enzyme glyceraldehyde-3-phosphate
      dehydrogenase. Through their actions on regulatory proteins, quinones affect
      various cell signaling pathways that promote and protect against inflammatory
      responses and cell damage. These actions vary with the specific quinone and its
      concentration. Effects of exposure to naphthoquinones as environmental chemicals
      can vary with the physical state, i.e., whether the quinone is particle bound or
      is in the vapor state. The exacerbation of pulmonary diseases by air pollutants
      can, in part, be attributed to quinone action.

PMID- 21942632
TI  - SILAC compatible strain of Pichia pastoris for expression of isotopically labeled
      protein standards and quantitative proteomics.
AB  - The methylotrophic yeast Pichia pastoris is a powerful eukaryotic platform for
      the production of heterologous protein. Recent publication of the P. pastoris
      genome has facilitated strain development toward biopharmaceutical and
      environmental science applications and has advanced the organism as a model
      system for the study of peroxisome biogenesis and methanol metabolism. Here we
      report the development of a P. pastoris arg-/lys- auxotrophic strain compatible
      with SILAC (stable isotope labeling by amino acids in cell culture) proteomic
      studies, which is capable of generating large quantities of isotopically labeled
      protein for mass spectrometry-based biomarker measurements. We demonstrate the
      utility of this strain to produce high purity human serum albumin uniformly
      labeled with isotopically heavy arginine and lysine. In addition, we demonstrate
      the first quantitative proteomic analysis of methanol metabolism in P. pastoris,
      reporting new evidence for a malate-aspartate NADH shuttle mechanism in the
      organism. This strain will be a useful model organism for the study of metabolism
      and peroxisome generation.

PMID- 21942635
TI  - Unichiral 2-(2'-pyrrolidinyl)-1,4-benzodioxanes: the 2R,2'S diastereomer of the N
      methyl-7-hydroxy analogue is a potent alpha4beta2- and alpha6beta2-nicotinic
      acetylcholine receptor partial agonist.
AB  - A series of unichiral 7-substituted 2-(1'-methyl-2'-pyrrolidinyl)-1,4
      benzodioxanes were synthesized and tested for the affinity for the alpha4beta2
      and alpha7 central nicotinic receptors; the 2R,2'S diastereomer of the 7-OH
      analogue [(R,S)-7], unique in the series, has a high alpha4beta2 affinity (12nM
      K(i)). N-Demethylation and configuration inversion of the stereocenters greatly
      weaken its alpha4beta2 affinity, confirming that such a rigid molecule can be
      considered a new template for alpha4beta2 ligands. Docking analysis showed how
      (R,S)-7 is capable of strongly and specifically interacting with the amino acidic
      counterpart of the alpha4beta2 receptor binding site. Further pharmacological
      characterization demonstrated that (R,S)-7 also has a high affinity for the
      alpha6beta2 receptor, and in vitro functional tests indicated that it is a potent
      alpha4beta2 and alpha6beta2 partial agonist, with modest affinity and potency for
      the alpha3beta4 receptor. Comparison with varenicline, a well-known nicotinic
      partial agonist used as a smoking cessation aid, interestingly reveals similar
      nicotinoid profiles.

PMID- 21942636
TI  - Nanoparticle-enhanced sensitivity of a nanogap-interdigitated electrode array
      impedimetric biosensor.
AB  - Interdigitated electrode (IDE) arrays with nanometer-scale gaps have been
      utilized to enhance the sensitivity of affinity-based detection. The geometry of
      nanogap IDEs was first optimized on the basis of simulations of the electric
      field and current density. It was determined that the gap (G) between the
      electrodes was the most important geometric parameter in determining the
      distribution and strength of the electric field and the current density compared
      to the width (W) and height (H) of the IDEs. Several devices were materialized
      and analyzed for their sensitivity to the electrochemical environment using
      faradic electrochemical impedance spectroscopy (EIS) as the detection technique.
      Nanogap optimized IDEs were then employed as biosensors for the label-free,
      affinity-based detection of antitissue transglutaminase antibodies (alphatTG
      Abs), a biomarker for the detection of autoimmune disorder celiac sprue,
      triggered by ingesting gluten. The label-free biosensor assay was found to be
      less sensitive compared to on-chip ELISA. Gold nanoparticles (GNPs) were then
      employed to improve the sensitivity of the nanogap IDE-based biosensor. With
      GNPs, the transducer sensitivity increased by 350% over that of label-free
      detection. The suitability of nanogap IDEs as biosensor transducers for EIS in
      label-free and GNP-labeled formats was established. The immunobiosensor assay
      detection sensitivity with the GNPs was found comparable to ELISA.

PMID- 21942638
TI  - The group's absence norm and commitment to the group as predictors of group
      member absence in the next session: an actor-partner analysis.
AB  - The group's absence norm, a construct from the applied psychology literature, was
      used to examine session absences in personal growth groups. Rather than examining
      the absence norm statically, we modeled it dynamically as a time-varying
      covariate (Tasca et al., 2010). We also examined moderation by modeling the
      interaction of the absence norm and the group member's commitment to the group in
      predicting the group member's absence in the next group session. Session absences
      in 1,722 group sessions for 66 group members in 9 interpersonal growth groups
      were modeled using Kenny, Mannetti, Pierro, Livi, and Kashy's (2002) adaptation
      of the Actor-Partner Interdependence model. Specifically, a 3-level model
      (sessions within group members within groups) examined the relationship of the
      group's absence norm (average previous absences of the other group members),
      commitment to the group (previous absences of the group member), and the
      interaction of the group's absence norm and commitment to the group on absence in
      the next session. As we hypothesized, (a) a greater number of previous individual
      absences (low commitment) increased the probability of a member being absent the
      next session, (b) the higher the group's absences norm, the greater the
      probability that an individual group member would be absent the next session, and
      (c) individual group members who were more committed to the group were more
      influenced by the group's absences norm than were group members less committed to
      the group. Implications for research and practice are discussed.

PMID- 21942637
TI  - Childhood abuse and neglect and cognitive flexibility in adolescents.
AB  - Childhood maltreatment (CM) has been associated with diminished executive
      functioning in children and adults; however, there is a relative paucity of study
      of executive function in adolescents exposed to CM. Yet, executive dysfunction in
      adolescence may have important adverse consequences including increased
      vulnerability to risky behaviors and impaired school functioning. This study
      investigates the relationship between self-reported CM and an executive function,
      cognitive flexibility, in adolescents without identified psychiatric disorders.
      Effects of physical and emotional, abuse and neglect, maltreatment subtypes were
      explored. Thirty adolescents ages 12-17 years, 50% females, completed the
      retrospective self-report Childhood Trauma Questionnaire (CTQ) and were
      administered the Wisconsin Card Sorting Test (WCST). Correlational analyses
      assessed the relationship between WCST perseverative error scores norm-referenced
      for age and education with CTQ total scores. The relationship with
      nonperseverative errors, as well as with physical and emotional abuse and neglect
      CM subscores, were explored. Total CTQ scores showed significant associations
      with perseverative errors on the WCST, but not with nonperseverative errors.
      Significant associations with perseverative errors were seen for physical abuse
      and physical neglect among the CTQ subscales. The results suggest both physical
      abuse and physical neglect are associated with diminished cognitive flexibility
      in adolescents. These effects were detected in adolescents without identified
      psychiatric diagnoses suggesting the importance of considering executive
      dysfunction in adolescents exposed to CM who may not meet diagnostic criteria for
      an Axis I disorder and that tests of perseverative errors, such as those of the
      WCST, may be sensitive indicators of this dysfunction.

PMID- 21942639
TI  - Synthesis of pH-activatable red fluorescent BODIPY dyes with distinct
      functionalities.
AB  - A series of tunable pH-dependent BODIPY dyes were synthesized and further
      functionalized in a Knoevenagel condensation reaction with various aldehydes. In
      this fashion, monofunctional dyes containing an alkyne, azide, or carboxylic acid
      (masked as its methyl ester) as ligation sites as well as asymmetrical
      bifunctional dyes were obtained, without compromising their pH-dependency. In
      addition, fluorescence excitation and emission maxima for these dyes were shown
      to be significantly red-shifted in comparison to their tetramethyl precursors.

PMID- 21942640
TI  - Prospective CCR5 small molecule antagonist compound design using a combined
      mutagenesis/modeling approach.
AB  - The viral resistance of marketed antiviral drugs including the emergence of new
      viral resistance of the only marketed CCR5 entry inhibitor, maraviroc, makes it
      necessary to develop new CCR5 allosteric inhibitors. A mutagenesis/modeling
      approach was used (a) to remove the potential hERG liability in an otherwise very
      promising series of compounds and (b) to design a new class of compounds with an
      unique mutant fingerprint profile depending on residues in the N-terminus and the
      extracellular loop 2. On the basis of residues, which were identified by
      mutagenesis as key interaction sites, binding modes of compounds were derived and
      utilized for compound design in a prospective manner. The compounds were then
      synthesized, and in vitro evaluation not only showed that they had good antiviral
      potency but also fulfilled the requirement of low hERG inhibition, a criterion
      necessary because a potential approved drug would be administered chronically.
      This work utilized an interdisciplinary approach including medicinal chemistry,
      molecular biology, and computational chemistry merging the structural
      requirements for potency with the requirements of an acceptable in vitro profile
      for allosteric CCR5 inhibitors. The obtained mutant fingerprint profiles of CCR5
      inhibitors were used to translate the CCR5 allosteric binding site into a general
      pharmacophore, which can be used for discovering new inhibitors.

PMID- 21942641
TI  - Family planning in Serbia--the perspective of female students from the University
      of Belgrade.
AB  - OBJECTIVES: To assess whether current knowledge and attitudes of future female
      doctors, pharmacists, politicians, journalists and social workers indicate that
      positive changes may take place in family planning in Serbia. METHODS: A total of
      504 female students from the University of Belgrade completed a questionnaire
      related to the physiology of reproduction, contraception, childbearing, and
      extended cycles of combined oral contraceptive (COC) use. RESULTS: Eighty percent
      of the study population knew the fertile period in the menstrual cycle. The
      students had positive opinions about COCs in 52% of the cases, and negative
      opinions in 48%. More than 80% of respondents were aware of the possibility of
      suppressing uterine bleeding by COC use, but only 22% would utilise COCs in that
      manner. Seventy-nine percent considered 25-29 years as the optimal age span for
      starting childbearing. Nearly all expressed the desire to have children later,
      with 2.56 being the average number of children wanted. CONCLUSION: Our findings
      indicate that professionals who, in the future, will provide education and
      counselling in the field of contraception, or will be involved in developing a
      national family planning framework in Serbia, are not likely to go about much
      differently from those presently active.

PMID- 21942642
TI  - Historical milestones in the development of tibolone (Livial(r)).
AB  - For a new chemical entity, tibolone had a very long development period of 25
      years before it was finally approved for the treatment of climacteric complaints.
      The reasons for this long development were its complex and fast metabolism and
      the poor standardization and sensitivity of analytical techniques and clinical
      methods. In the beginning of the new millennium, the results of primate studies
      and dose-finding studies in early postmenopausal women showed that tibolone had
      clear tissue-selective effects: it prevented hot flushes and bone loss, which are
      estrogen-related effects, while the estrogen-sensitive organs like breast and
      endometrium were not stimulated. In tissue, measurements of tibolone metabolites
      revealed that estrogenic metabolites were present in brain, but these metabolites
      were found as inactive conjugates in breast and endometrium. Attempts to find new
      indications for tibolone in large clinical trials failed because these studies
      were performed in elderly women who had already past the menopause many years ago
      and so unexpected side-effects became apparent due to altered metabolism and gene
      activation.

PMID- 21942643
TI  - An ester enolate-Claisen rearrangement route to substituted 4-alkylideneprolines.
      studies toward a definitive structural revision of lucentamycin A.
AB  - Substituted 4-alkylideneprolines represent a rare class of naturally occurring
      amino acids with promising biological activities. Lucentamycin A is a cytotoxic,
      marine-derived tripeptide that harbors a 4-ethylidine-3-methylproline (Emp)
      residue unique among known peptide natural products. In this paper, we examine
      the synthesis of Emp and related 4-alkylideneprolines employing a versatile ester
      enolate-Claisen rearrangement. The scope and selectivity of the key rearrangement
      reaction are described with a number of diversely substituted glycine ester
      substrates. Treatment of the allyl esters with excess NaHMDS at ambient
      temperature gives rise to highly substituted alpha-allylglycine products with
      good to excellent diastereoselectivities. Resolution of dipeptide diastereomers
      and cyclization to form the pyrrolidine rings provide rapid access to stereopure
      prolyl dipeptides. We have applied this strategy to the synthesis of four Emp
      containing isomers of lucentamycin A in pursuit of a definitive stereochemical
      revision of the natural product. Our studies indicate that the Emp stereogenic
      centers are not the source of structural misassignment. The current strategy
      should find broad utility in the synthesis of additional natural product
      analogues and related 3-alkyl-4-alkylidene prolines.

PMID- 21942644
TI  - Adsorption of ethane, ethylene, propane, and propylene on a magnesium-based metal
      organic framework.
AB  - Separation of olefin/paraffin is an energy-intensive and difficult separation
      process in petrochemical industry. Energy-efficient adsorption process is
      considered as a promising alternative to the traditional cryogenic distillation
      for separating olefin/paraffin mixtures. In this work, we explored the
      feasibility of adsorptive separation of olefin/paraffin mixtures using a
      magnesium-based metal-organic framework, Mg-MOF-74. Adsorption equilibria and
      kinetics of ethane, ethylene, propane, and propylene on a Mg-MOF-74 adsorbent
      were determined at 278, 298, and 318 K and pressures up to 100 kPa. A dual-site
      Sips model was used to correlate the adsorption equilibrium data, and a micropore
      diffusion model was applied to extract the diffusivities from the adsorption
      kinetics data. A grand canonical Monte Carlo simulation was conducted to
      calculate the adsorption isotherms and to elucidate the adsorption mechanisms.
      The simulation results showed that all four adsorbate molecules are
      preferentially adsorbed on the open metal sites where each metal site binds one
      adsorbate molecule. Propylene and propane have a stronger affinity to the Mg-MOF
      74 adsorbent than ethane and ethylene because of their significant dipole
      moments. Adsorption equilibrium selectivity, combined equilibrium and kinetic
      selectivity, and adsorbent selection parameter for pressure swing adsorption
      processes were estimated. The relatively high values of adsorption selectivity
      suggest that it is feasible to separate ethylene/ethane, propylene/propane, and
      propylene/ethylene pairs in a vacuum swing adsorption process using Mg-MOF-74 as
      an adsorbent.

PMID- 21942645
TI  - Bulk synthesis of crystalline and crystalline core/amorphous shell silicon
      nanowires and their application for energy storage.
AB  - Silicon nanowires (NWs) have stimulated significant interest and found numerous
      applications; however, many applications will require a bulk quantity of
      nanowires to be synthesized in a reliable way. In this paper, we report the bulk
      synthesis of silicon nanowires on millimeter scale Al(2)O(3) spheres with a
      thermal chemical vapor deposition system (CVD) via the vapor-liquid-solid (VLS)
      growth mechanism. The spherical substrates enable the realization of Si nanowire
      synthesis on three-dimensional surfaces in comparison with the synthesis on a
      planar, two-dimensional wafer substrate. By modifying temperature in the recipe
      of synthesis, both single-crystalline and crystalline core/amorphous shell Si
      nanowires were obtained with this nanowire-on-spherical-support method.
      Conspicuous distinction in crystallinity of the nanowires was revealed by
      transmission electron microscopy characterization. The crystalline core/amorphous
      shell Si nanowires were utilized to form the anode of Li-ion battery half-cells
      with the traditional slurry method. Galvanostatic measurement demonstrated that
      the maximum power capacity achievable by the electrodes was 3500 mAh/g and
      capacity sustained at 1100 mAh/g after 60 cycles of charging and discharging.

PMID- 21942647
TI  - Natural sulforaphane as a functional chemopreventive agent: including a review of
      isolation, purification and analysis methods.
AB  - Epidemiological data show that a diet rich in fruits and vegetables can reduce
      the risk from a number of cancers and chronic diseases. Sulforaphane (SF), a
      phytochemical constituent of cruciferous vegetables, has been widely researched
      in recent decades as a potential chemopreventive compound. Nonexistent in intact
      vegetables, natural SF, is formed from glucoraphanin hydrolyzed by myrosinase.
      This review summarizes and compares different analysis, isolation and
      purification methods engaged in SF research. Major important chemopreventive
      properties of SF investigated in existing research are reviewed and discussed,
      including antioxidant, anticarcinogenic and anti-inflammatory functions.
      Considering the potential applications of SF in the future, metabolism, stability
      and formulation developments of SF are also discussed. Research opportunities are
      identified based on the review of existing studies to facilitate future
      explorations on SF, a promising natural compound in chemopreventive therapy.

PMID- 21942648
TI  - Study and characterization of polyphenol oxidase from eggplant (Solanum melongena
      L.).
AB  - In this study the catecholase and cresolase activities of eggplant polyphenol
      oxidase (PPO) were investigated. Enzyme activity was determined by measuring the
      increase in absorbance using catechol as substrate and 3-methyl-2
      benzothiazolinone hydrazone (MBTH) as coupled reagent. The effects of substrate
      specificity, heat inactivation, temperature, pH, and inhibitors were investigated
      to understand the enzymatic alteration of ready-to-eat preparations. Browning of
      vegetables was determined through a colorimeter. Decrease of lightness (L*) and
      increase of color difference values (DeltaE*) were correlated with tissue
      browning. Antibrowning agents were tested on PPO under the same conditions. The
      enzyme activity was strongly inhibited by 0.4 M citric acid. Under natural pH
      conditions, the enzyme was also inhibited by tartaric acid and acetic acid. All
      of the results were used to understand the best conditions for food
      transformation (ready-to-eat and grilled eggplant slices).

PMID- 21942646
TI  - MALDI imaging of lipid biochemistry in tissues by mass spectrometry.

PMID- 21942649
TI  - Inactivation of transcription factor pit-1 to target tumoral somatolactotroph
      cells.
AB  - The treatment of growth hormone (GH)- and prolactin (PRL)-secreting tumors
      resistant to current therapeutic molecules (somatostatin and dopamine analogues)
      remains challenging. To target these tumors specifically, we chose to inactivate
      a gene coding for a crucial factor in cell proliferation and hormonal regulation,
      specifically expressed in pituitary, by using a dominant-negative form of this
      gene involved in human pituitary deficiencies: transcription factor Pit-1
      (POU1F1) mutated on arginine 271 to tryptophan (R271W). After lentiviral
      transfer, the effect of R271W was studied in vitro on human tumoral somatotroph
      and lactotroph cells and on the murine mammosomatotroph cell line GH4C1 and in
      vivo on GH4C1 subcutaneous xenografts in nude mice. R271W induced a decrease in
      GH and PRL hypersecretion by controlling the transcription of the corresponding
      hormones. This mutant decreased cell viability by an apoptotic mechanism and in
      vivo blocked the tumoral growth and GH secretion of xenografts obtained after
      transplantation of GH4C1 expressing mutant R271W. The strategy of using a
      dominant-negative form of a main factor controlling cell proliferation and
      hormonal secretion, and exclusively expressed in pituitary, seems promising for
      the gene therapy of human pituitary tumors and may be translated to other types
      of tumors maintaining some differentiation features.

PMID- 21942650
TI  - Tandem GA residues on opposite sides of the loop in molecular beacon-like DNA
      hairpins compact the loop and increase hairpin stability.
AB  - The free solution electrophoretic mobilities and thermal stabilities of hairpins
      formed by two complementary 26-nucleotide oligomers have been measured by
      capillary electrophoresis. The oligomers are predicted to form molecular beacon
      like hairpins with 5 bp stems and 16 nucleotides in the loop. One hairpin, called
      hairpin2 (hp2), migrates with a relatively fast free solution mobility and
      exhibits melting temperatures that are reasonably well predicted by the popular
      structure-prediction program Mfold. Its complement, called hairpin1 (hp1),
      migrates with a slower free solution mobility and forms a stable hairpin only in
      solutions containing >=200 mM Na(+). The melting temperatures observed for hp1
      are ~18  degrees C lower than those observed for hp2 and ~20  degrees C lower
      than those predicted by Mfold. The greater thermal stability of hp2 is due to the
      presence of tandem GA residues on opposite sides of the loop. If the
      corresponding TC residues in the hp1 loop are replaced by tandem GA residues, the
      melting temperatures of the modified hairpin are close to those observed for hp2.
      Eliminating the tandem GA residues in the hp2 loop significantly decreases the
      thermal stability of hp2. If the loops are replaced by a loop of 16 thymine
      residues, the free solution mobilities and thermal stabilities of the T-loop
      hairpin are equal to those observed for hp1. Hence, the loop of hp1 appears to be
      relatively unstructured, with few base-base stacking interactions. Interactions
      between tandem GA residues on opposite sides of the hp2 loop appear to compact
      the loop and increase hairpin stability.

PMID- 21942651
TI  - Large-scale identification of bacteria-host crosstalk by affinity chromatography:
      capturing the interactions of Streptococcus suis proteins with host cells.
AB  - Protein-protein interactions between bacteria and their hosts are responsible for
      all types of infection processes. The investigation of the bacteria-host
      crosstalk can provide a comprehensive understanding of the pathogenesis of
      bacterial disease. Despite scattered efforts in this field, a systematic
      identification of interactions between host and bacterial proteins remains
      unavailable. Here, we develop ACSP (affinity chromatography-based surface
      proteomics), which combines affinity chromatography and shotgun proteomics (LC
      MS/MS), to investigate the interactions on a large-scale. Using ACSP, the
      potential surface interacting proteins (SIPs) of Streptococcus suis serotype 2
      (SS2) were captured by the chromatographic resin, which was immobilized with the
      native surface molecules of Hep-2 cells. And then 40 potential SIPs were
      identified from the preys by LC-MS/MS, including 3 SIPs that have been previously
      reported in the literature. We selected 8 important SIPs and confirmed their
      ability to adhere to Hep-2 cells. Additionally, 3 newly identified SIPs, or their
      polyclonal antibodies, were found to significantly inhibit the adherence of SS2
      to Hep-2 cells, indicating their essential role in the interaction between SS2
      and Hep-2 cells. Using this example, we show that ACSP represents a new valuable
      tool for investigating the bacteria-host interactions.

PMID- 21942652
TI  - Synthesis of high crystallinity ZnO nanowire array on polymer substrate and
      flexible fiber-based sensor.
AB  - Well aligned ZnO nanowire (NW) arrays are grown on Kevlar fiber and Kapton film
      via the chemical vapor deposition (CVD) method. These NWs have better
      crystallinity than those synthesized through the low-temperature hydrothermal
      method. The average length and diameter of ZnO NWs grown on Kevlar fiber can be
      controlled from 0.5 to 2.76 MUm and 30 to 300 nm, respectively. A flexible
      ultraviolet (UV) sensor based on Kevlar fiber/ZnO NWs hybrid structure is made to
      detect UV illumination quantificationally.

PMID- 21942653
TI  - Parent and child experiences of neuropsychological assessment as a function of
      child feedback by individualized fable.
AB  - This study evaluated whether receiving developmentally appropriate feedback in
      the form of individualized fables would affect how children and their parents
      reported experiencing a neuropsychological assessment. Participants were 32
      children who underwent a neuropsychological assessment, along with one of their
      parents. The evaluation process, including the provision of parent feedback, was
      standard for the setting, a private practice of neuropsychology. The only
      addition was the provision of child feedback through a fable, given to the
      experimental group prior to the collection of research measures and to the
      comparison group after the collection of research data. Multivariate and
      univariate statistics were used to test differences between the two groups.
      Results indicated that children in the experimental group reported a greater
      sense of learning about themselves, a more positive relationship with their
      assessor, a greater sense of collaboration with the assessment process, and a
      sense that their parents learned more about them because of the assessment than
      did children in the comparison group. Parents in the experimental group reported
      a more positive relationship between their child and the assessor, a greater
      sense of collaboration with the assessment process, and higher satisfaction with
      clinic services compared to the comparison group. Limitations and implications
      for future research and assessment practice with children are discussed. 

PMID- 21942654
TI  - Palladium-catalyzed selective carboelimination and cross-coupling reactions of
      benzocyclobutenols with aryl bromides.
AB  - The palladium-catalyzed selective beta-carboelimination and cross-coupling
      chemistry of benzocyclobutenols is described. In contrast to the base-mediated
      ring-opening reactions of benzocyclobutenols, this variant proceeds with
      exclusive cleavage of the proximal bond.

PMID- 21942655
TI  - Effect of 1-year, low-dose DHEA therapy on climacteric symptoms and female
      sexuality.
AB  - BACKGROUND: Sexual desire is affected by endocrine and psychosocial factors.
      Menopausal hormonal changes are relevant to the causes of sexual dysfunction
      during reproductive aging. AIM: To evaluate the effects of different types of
      hormonal replacement therapy (HRT) on sexual function, frequency of sexual
      intercourse, and quality of relationship in early postmenopausal women. We
      recruited 48 healthy postmenopausal women aged 50-60 years (mean age 54.5 +/- 3.3
      years). Women with climacteric symptoms were uniformly randomized into three
      groups receiving either dehydroepiandrosterone (DHEA 10 mg) daily, or daily oral
      estradiol (1 mg) plus dihydrogesterone (5 mg), or daily oral tibolone (2.5 mg)
      for 12 months. Women who refused hormonal therapy were treated with oral vitamin
      D (400 IU). Efficacy was evaluated using the McCoy Female Sexuality Questionnaire
      before treatment and after 12 months. We evaluated the hormonal profile before
      treatment and after 3, 6 and 12 months. RESULTS: The groups receiving DHEA or HRT
      reported a significant improvement in sexual function compared to baseline (p <
      0.001 and p < 0.01, respectively) using the McCoy total score. The quality of
      relationship was similar at baseline and after 3, 6 and 12 months of treatment.
      There were significant increases in the numbers of episodes of sexual intercourse
      in the previous 4 weeks in women treated with DHEA, HRT and tibolone in
      comparison with the baseline value (p < 0.01, p < 0.05, p < 0.01, respectively).
      No changes in the McCoy score occurred in women receiving vitamin D. CONCLUSIONS:
      Daily oral DHEA therapy at the dose of 10 mg, HRT and tibolone all provided a
      significant improvement in comparison with vitamin D in sexual function and in
      frequency of sexual intercourse in early postmenopausal women.

PMID- 21942656
TI  - Hindered coarsening of a phase-separating microemulsion due to dispersed
      colloidal particles.
AB  - The addition of sterically stabilized colloidal particles to a phase-separating
      microemulsion leads to dramatic changes in its demixing behavior, especially
      during the later stages. Our microemulsion is composed of reverse micelles of
      sodium dodecyl sulfate, pentanol, and water in a dodecane continuous phase which
      separates into micelle-rich and micelle-poor phases above a lower critical
      solution temperature. The poly(methyl methacrylate) particles preferentially
      partition into the less structured, micelle-poor phase. Nucleation of the
      minority phase or spinodal decomposition close to criticality continue to occur
      in the presence of particles, albeit with pronounced pretransitional clustering
      of particles when the micelle-poor phase is in the minority. The coalescence of
      micelle-poor droplets and the coarsening of micelle-rich domains are both
      strongly modified due to the presence of colloidal particles. We use our
      observations of the early stages of phase separation to understand these late
      stage changes.

PMID- 21942657
TI  - Levonorgestrel releasing-intrauterine system for the treatment of menorrhagia
      and/or frequent irregular uterine bleeding associated with uterine leiomyoma.
AB  - OBJECTIVE: To evaluate the effectiveness of the levonorgestrel releasing
      intrauterine system (LNG-IUS) in the treatment of menorrhagia and/or frequent
      irregular uterine bleeding in women with uterine myomas. STUDY DESIGN:
      Prospective study whereby 102 women with intramural myomas (in a few cases
      associated with submucous or subserous myomas), suffering from menorrhagia and/or
      frequent irregular uterine bleeding, were evaluated by means of the Pictorial
      Blood Assessment Chart (PBAC; Higham score) and ultrasound, three, six and 12
      months after insertion of a LNG-IUS. RESULTS: The PBAC score dropped (from a mean
      value of 231.7 to 17.6 at 12 months). The duration of menstrual bleeding
      diminished significantly (p<0.001). Uterine volume decreased from a mean of 145
      cm3 to 129 cm3 at 12 months (p=0.01). Changes in the volume of the myomas were
      not statistically significant (p=0.23). Satisfaction rate was good in 91 cases
      (89%), fair in four cases (4%), and poor in seven cases (7%). During the one-year
      period of follow-up, 11 cases of expulsion or removal of the LNG-IUS were
      recorded. CONCLUSION: The LNG-IUS is effective in controlling heavy menorrhagia
      and/or frequent irregular uterine bleeding related to the presence of myomas, but
      has no significant effect on the size of the tumours.

PMID- 21942658
TI  - Zinc-catalyzed allenylations of aldehydes and ketones.
AB  - The general zinc-catalyzed allenylation of aldehydes and ketones with an allenyl
      boronate is presented. Preliminary mechanistic studies support a kinetically
      controlled process wherein, after a site-selective B/Zn exchange to generate a
      propargyl zinc intermediate, the addition to the electrophile effectively
      competes with propargyl-allenyl zinc equilibration. The utility of the
      methodology was demonstrated by application to a rhodium-catalyzed [4+2]
      cycloaddition.

PMID- 21942659
TI  - Transferable and flexible nanorod-assembled TiO2 cloths for dye-sensitized solar
      cells, photodetectors, and photocatalysts.
AB  - Flexible and transferable TiO(2) nanorods cloths (TNRCs) were synthesized from a
      fast and catalyst-free microwave heating route by using carbon cloth as an
      efficiently sacrificial template. The as-synthesized TNRCs were assembled by
      numerous aligned TiO(2) nanorods with diameters of about 100 nm. The good
      transferability and flexibility make it possible to be transferred to any
      substrate for further device applications. As an example, we transferred the
      TNRCs to a FTO substrate to make dye-sensitized solar cells, which exhibited an
      improved efficiency of around 2.21% assisted by TiCl(4) treatment. The
      transferable TNRCs were also configured as high-performance photodetectors.
      Illuminated by UV light with a wavelength of 365 nm, the current was found
      significantly enhanced, and an I(UV)/I(dark) of about 60, a rise time of nearly
      1.4 s, and a decay time of 6.1 s were obtained. Moreover, they were also
      configured as flexible and recyclable photocatalysts with good photocatalytic
      performance for the degradation of methylene blue solution under UV light
      irradiation.

PMID- 21942661
TI  - The role of local and distal landmarks in the development of object location
      memory.
AB  - To locate objects in the environment, animals and humans use visual and nonvisual
      information. We were interested in children's ability to relocate an object on
      the basis of self-motion and local and distal color cues for orientation. Five-
      to 9-year-old children were tested on an object location memory task in which,
      between presentation and test, the availability of local and distal cues was
      manipulated. Additionally, participants' viewpoint could be changed. We used a
      Bayesian model selection approach to compare our hypotheses. We found that, to
      remain oriented in space, 5-year-olds benefit from visual information in general,
      7-year-olds benefit from visual cues when a viewpoint change takes place, and 9
      year-olds do not benefit from the availability of visual cues for orientation but
      rely on self-movement cues instead. Results are discussed in terms of the
      adaptive combination model (Newcombe & Huttenlocher, 2006).

PMID- 21942662
TI  - Retrospective recall of sexual orientation identity development among gay,
      lesbian, and bisexual adults.
AB  - Although recent attention has focused on the likelihood that contemporary sexual
      minority youth (i.e., gay, lesbian, bisexual [GLB]) are "coming out" at younger
      ages, few studies have examined whether early sexual orientation identity
      development is also present in older GLB cohorts. We analyzed retrospective data
      on the timing of sexual orientation milestones in a sample of sexual minorities
      drawn from the California Quality of Life Surveys. Latent profile analysis of
      1,260 GLB adults, ages 18-84 years, identified 3 trajectories of development:
      early (n = 951; milestones spanning ages 12-20), middle (n = 239; milestones
      spanning ages 18-31), and late (n = 70; milestones spanning ages 32-43).
      Motivated by previous research on variability in adolescent developmental
      trajectories, we identified 2 subgroups in post hoc analyses of the early profile
      group: child onset (n = 284; milestones spanning ages 8-18) and teen onset (n =
      667; milestones spanning ages 14-22). Nearly all patterns of development were
      identity centered, with average age of self-identification as GLB preceding
      average age of first same-sex sexual activity. Overall, younger participants and
      the majority of older participants were classified to the early profile,
      suggesting that early development is common regardless of age cohort. The
      additional gender differences observed in the onset and pace of sexual
      orientation identity development warrant future research.

PMID- 21942663
TI  - Control networks and neuromodulators of early development.
AB  - In adults, most cognitive and emotional self-regulation is carried out by a
      network of brain regions, including the anterior cingulate, insula, and areas of
      the basal ganglia, related to executive attention. We propose that during
      infancy, control systems depend primarily upon a brain network involved in
      orienting to sensory events that includes areas of the parietal lobe and frontal
      eye fields. Studies of human adults and alert monkeys have shown that the brain
      network involved in orienting to sensory events is moderated primarily by the
      nicotinic cholinergic system arising in the nucleus basalis. The executive
      attention network is primarily moderated by dopaminergic input from the ventral
      tegmental area. A change from cholinergic to dopaminergic modulation would be a
      consequence of this switch of control networks and may be important in
      understanding early development. We trace the attentional, emotional, and
      behavioral changes in early development related to this developmental change in
      regulative networks and their modulators.

PMID- 21942664
TI  - The development of memory efficiency and value-directed remembering across the
      life span: a cross-sectional study of memory and selectivity.
AB  - Although attentional control and memory change considerably across the life span,
      no research has examined how the ability to strategically remember important
      information (i.e., value-directed remembering) changes from childhood to old age.
      The present study examined this in different age groups across the life span (N =
      320, 5-96 years old). A selectivity task was used in which participants were
      asked to study and recall items worth different point values in order to maximize
      their point score. This procedure allowed for measures of memory
      quantity/capacity (number of words recalled) and memory efficiency/selectivity
      (the recall of high-value items relative to low-value items). Age-related
      differences were found for memory capacity, as young adults recalled more words
      than the other groups. However, in terms of selectivity, younger and older adults
      were more selective than adolescents and children. The dissociation between these
      measures across the life span illustrates important age-related differences in
      terms of memory capacity and the ability to selectively remember high-value
      information.

PMID- 21942665
TI  - Implicit associations with popularity in early adolescence: an approach-avoidance
      analysis.
AB  - This study examined 241 early adolescents' implicit and explicit associations
      with popularity. The peer status and gender of both the targets and the
      perceivers were considered. Explicit associations with popularity were assessed
      with sociometric methods. Implicit associations with popularity were assessed
      with an approach-avoidance task (AAT). Explicit evaluations of popularity were
      positive, but implicit associations were negative: Avoidance reactions to popular
      peers were faster than approach reactions. Interactions with the status of the
      perceiver indicated that unpopular participants had stronger negative implicit
      reactions to popular girls than did popular participants. This study demonstrated
      a negative reaction to popularity that cannot be revealed with explicit methods.
      The study of implicit processes with methods such as the AAT is a new and
      important direction for peer relations research.

PMID- 21942666
TI  - From racial discrimination to risky sex: prospective relations involving peers
      and parents.
AB  - This study investigated how early experience with racial discrimination affected
      the subsequent risky sexual behaviors of a diverse sample of African American
      youths (N = 745). The analyses focused on 3 risk-promoting factors thought to
      mediate the hypothesized discrimination -> risky sex relation: negative affect,
      affiliation with deviant peers, and favorable attitudes toward risky sex. In
      addition, attentive parenting was examined as a protective factor. Analyses using
      structural equation modeling revealed that youths who perceived more racial
      discrimination at age 10 or 11 were engaging in more sexual risk taking at age 18
      or 19. This relation was mediated by the hypothesized risk-promoting factors via
      pathways that were consistent with our conceptual model. Results also indicated a
      prospective reciprocal relation between parenting and children's deviant
      affiliations: deviant peer affiliations at age 10 or 11 predicted more attentive
      parenting behaviors by the parents; this response from the parents, in turn,
      predicted relatively fewer deviant affiliations when the youths were 15 or 16.
      Study findings are discussed in terms of their relevance to the
      disproportionately high rates of sexually transmitted infections among African
      Americans.

PMID- 21942667
TI  - Cognitive predictors of achievement growth in mathematics: a 5-year longitudinal
      study.
AB  - The study's goal was to identify the beginning of 1st grade quantitative
      competencies that predict mathematics achievement start point and growth through
      5th grade. Measures of number, counting, and arithmetic competencies were
      administered in early 1st grade and used to predict mathematics achievement
      through 5th (n = 177), while controlling for intelligence, working memory, and
      processing speed. Multilevel models revealed intelligence and processing speed,
      and the central executive component of working memory predicted achievement or
      achievement growth in mathematics and, as a contrast domain, word reading. The
      phonological loop was uniquely predictive of word reading and the visuospatial
      sketch pad of mathematics. Early fluency in processing and manipulating numerical
      set size and Arabic numerals, accurate use of sophisticated counting procedures
      for solving addition problems, and accuracy in making placements on a
      mathematical number line were uniquely predictive of mathematics achievement. Use
      of memory-based processes to solve addition problems predicted mathematics and
      reading achievement but in different ways. The results identify the early
      quantitative competencies that uniquely contribute to mathematics learning.

PMID- 21942668
TI  - Children's sleep and cognitive performance: a cross-domain analysis of change
      over time.
AB  - Relations between changes in children's cognitive performance and changes in
      sleep problems were examined over a 3-year period, and family socioeconomic
      status, child race/ethnicity, and gender were assessed as moderators of these
      associations. Participants were 250 second- and third-grade (8-9 years old at
      Time 1) boys and girls. At each assessment, children's cognitive performance
      (Verbal Comprehension, Decision Speed) was measured using the Woodcock-Johnson
      III Tests of Cognitive Abilities, and sleep problems (Sleepiness, Sleep/Wake
      Problems) were collected via self-report. Individual growth models revealed that
      children who reported increases in Sleepiness exhibited little growth in Verbal
      Comprehension over time compared with their peers who reported decreases in
      Sleepiness, resulting in a nearly 11-point cognitive deficit by the end of the
      study. These associations were not found for Sleep/Wake Problems or Decision
      Speed. Child race/ethnicity and gender moderated these associations, with
      Sleepiness serving as a vulnerability factor for poor cognitive outcomes,
      especially among African American children and girls. Differences in cognitive
      performance for children with high and low Sleepiness trajectories ranged from 16
      to 19 points for African American children and from 11 to 19 points for girls.
      Results build substantially on existing literature examining associations between
      sleep and cognitive functioning in children and are the first to demonstrate that
      children's sleep trajectories over 3 waves were associated with changes in their
      cognitive performance over time.

PMID- 21942669
TI  - Automated gaze-contingent objects elicit orientation following in 8-month-old
      infants.
AB  - The current study tested whether the purely amodal cue of contingency elicits
      orientation following behavior in 8-month-old infants. We presented 8-month-old
      infants with automated objects without human features that did or did not react
      contingently to the infants' fixations recorded by an eye tracker. We found that
      an object's occasional orientation toward peripheral targets was reciprocated by
      a congruent visual orientation following response by infants only when it had
      displayed gaze-contingent interactivity. Our finding demonstrates that infants'
      gaze-following behavior does not depend on the presence of a human being. The
      results are consistent with the idea that, in 8-month-old infants, the detection
      of contingent reactivity, like other communicative signals, can itself elicit the
      illusion of being addressed.

PMID- 21942671
TI  - Cation-anion hydrogen bonds: a new class of hydrogen bonds that extends their
      strength beyond the covalent limit. A theoretical characterization.
AB  - The existence of O-H...O hydrogen bonds having a strength within the -80 to -210
      kcal/mol range, that is, in the range of strength of covalent bonds and well
      beyond the so-called covalent limit (-50 kcal/mol), is reported on complexes
      where the O-H proton donor and O acceptor groups are located in ions of opposite
      sign. A complete analysis of short distance O-H...O hydrogen bonds between
      charged fragments was performed for cases where the OH and O groups are both
      located on charged molecules. It shows that these interactions (a) are
      nonsymmetrical for the O-H and H...O distances, (b) have a noncovalent H...O bond
      critical point, and (c) have a strong and energetically stable electrostatic
      component when the OH and O groups are located in oppositely charged molecules.
      These cation-anion O-H...O interactions are energetically stable, satisfy the
      usual topology for hydrogen bonds, HBs, and also have the same directionality
      found in other HBs. Therefore, they should be considered as a new class of HBs,
      the cation-anion hydrogen bonds.

PMID- 21942676
TI  - Engineering a structure switching mechanism into a steroid-binding aptamer and
      hydrodynamic analysis of the ligand binding mechanism.
AB  - The steroid binding mechanism of a DNA aptamer was studied using isothermal
      titration calorimetry (ITC), NMR spectroscopy, quasi-elastic light scattering
      (QELS), and small-angle X-ray spectroscopy (SAXS). Binding affinity determination
      of a series of steroid-binding aptamers derived from a parent cocaine-binding
      aptamer demonstrates that substituting a GA base pair with a GC base pair governs
      the switch in binding specificity from cocaine to the steroid deoxycholic acid
      (DCA). Binding of DCA to all aptamers is an enthalpically driven process with an
      unfavorable binding entropy. We engineered into the steroid-binding aptamer a
      ligand-induced folding mechanism by shortening the terminal stem by two base
      pairs. NMR methods were used to demonstrate that there is a transition from a
      state where base pairs are formed in one stem of the free aptamer, to where three
      stems are formed in the DCA-bound aptamer. The ability to generate a ligand
      induced folding mechanism into a DNA aptamer architecture based on the three-way
      junction of the cocaine-binding aptamer opens the door to obtaining a series of
      aptamers all with ligand-induced folding mechanisms but triggered by different
      ligands. Hydrodynamic data from diffusion NMR spectroscopy, QELS, and SAXS show
      that for the aptamer with the full-length terminal stem there is a small amount
      of structure compaction with DCA binding. For ligand binding by the short
      terminal stem aptamer, we propose a binding mechanism where secondary structure
      forms upon DCA binding starting from a free structure where the aptamer exists in
      a compact form.

PMID- 21942678
TI  - Hearing help-seeking and rehabilitation: perspectives of adults with hearing
      impairment.
AB  - OBJECTIVE: This study investigated the perspectives of adults with hearing
      impairment on hearing help-seeking and rehabilitation. DESIGN: Individual semi
      structured interviews were completed. STUDY SAMPLE: In total, 34 adults with
      hearing impairment in four countries (Australia, Denmark, UK, and USA)
      participated. Participants had a range of experience with hearing help-seeking
      and rehabilitation, from never having sought help to being satisfied hearing-aid
      users. RESULTS: Qualitative content analysis identified four main categories
      ('perceiving my hearing impairment', 'seeking hearing help', 'using my hearing
      aids', and 'perspectives and knowledge') and, at the next level, 25 categories.
      This article reports on the densest categories: they are described, exemplified
      with interview quotes, and discussed. CONCLUSIONS: People largely described
      hearing help-seeking and rehabilitation in the context of their daily lives.
      Adults with hearing impairment rarely described clinical encounters towards
      hearing help-seeking and rehabilitation as a connected process. They portrayed
      interactions with clinicians as isolated events rather than chronologically
      ordered steps relating to a common goal. Clinical implications of the findings
      are discussed.

PMID- 21942679
TI  - Comprehensive proteome analysis of hippocampus, brainstem, and spinal cord from
      paralytic and furious dogs naturally infected with rabies.
AB  - Paralytic and furious forms are unique clinical entities of rabies in humans and
      dogs. However, molecular mechanisms underlying these disorders remained unclear.
      We investigated changes in proteomes of the hippocampus, brainstem and spinal
      cord of paralytic and furious dogs naturally infected with rabies compared to
      noninfected controls. Proteins were extracted from these tissues and analyzed by
      two-dimensional gel electrophoresis (2-DE) (n = 6 gels/region in each group, a
      total of 54 gels were analyzed). From >1000 protein spots visualized in each gel,
      spot matching, quantitative intensity analysis, and ANOVA with Tukey's posthoc
      multiple comparisons revealed 32, 49, and 67 protein spots that were
      differentially expressed among the three clinical groups in the hippocampus,
      brainstem and spinal cord, respectively. These proteins were then identified by
      quadrupole time-of-flight mass spectrometry and tandem mass spectrometry (Q-TOF
      MS and MS/MS), including antioxidants, apoptosis-related proteins, cytoskeletal
      proteins, heat shock proteins/chaperones, immune regulatory proteins, metabolic
      enzymes, neuron-specific proteins, transcription/translation regulators,
      ubiquitination/proteasome-related proteins, vesicular transport proteins, and
      hypothetical proteins. Among these, 13, 17, and 41 proteins in the hippocampus,
      brainstem and spinal cord, respectively, significantly differed between paralytic
      and furious forms and thus may potentially be biomarkers to differentiate these
      two distinct forms of rabies. In summary, we report herein for the first time a
      large data set of changes in proteomes of the hippocampus, brainstem and spinal
      cord in dogs naturally infected with rabies. These data will be useful for better
      understanding of molecular mechanisms of rabies and for differentiation of its
      paralytic and furious forms.

PMID- 21942681
TI  - Service user views and service user research in the Journal of mental health.

PMID- 21942680
TI  - Increase of the activity of phase II antioxidant enzymes in rats after a single
      dose of coffee.
AB  - This study evaluated the acute effect of the administration of coffee brew in the
      activity of phase II antioxidant enzymes in the hepatic tissue of rats. A single
      dose of this beverage increased the activity of the enzymes SOD, CAT, and GPx;
      the maximum increase occurred 1 h after administration (19.1, 22.1, and 25.1%,
      respectively). These changes were statistically significant (p < 0.05), the
      response was shown to be dose-dependent (p < 0.05), and the return to basal
      levels took >4 h from the intervention, suggesting a long-term effect. The total
      antioxidant capacity of the hepatic tissue also exhibited a peak 1 h after the
      intervention (6.5%), but the increase was not statistically significant and the
      response was not dose-dependent due to the low exposure to coffee. These results
      indicate that coffee increases the activities of antioxidant enzymes, improving
      protection against oxidative stress.

PMID- 21942682
TI  - Mental health impairment associated with eating-disorder features in a community
      sample of women.
AB  - BACKGROUND AND AIMS:  Impairment in mental health associated with eating-disorder
      features was examined in a large, general population sample of women aged 18 to
      42 years. METHOD:  Participants (n = 5255) completed self-report measures of
      eating-disordered behaviour, mental health functioning, height and weight and
      socio-demographic information. RESULTS: The most common eating-disorder features
      were extreme concerns about weight or shape (14.6%), subjective overeating
      (12.7%), objective overeating (10.6%) and extreme concerns about dietary intake
      (10.4%). In multivariable analysis, in which mental health functioning was
      regressed on eating-disorder features, while also controlling for age and body
      weight, objective overeating (beta  =  -0.07), subjective overeating (beta   = 
      0.07), extreme dietary restriction (beta  =  -0.06) and extreme concerns about
      eating (beta  =  -0.04) showed small, but statistically significant associations
      with mental health impairment, whereas extreme weight or shape concerns showed a
      very strong association (beta  =  -0.24). CONCLUSIONS: From a clinical
      perspective, the findings are consistent with the importance attached to the
      "over-evaluation" of weight or shape as a core component of eating-disorder
      psychopathology. From a public health perspective, the findings indicate the need
      to conceive of body dissatisfaction as a target for health promotion in its own
      right.

PMID- 21942683
TI  - Improving therapeutic use of homework: suggestions from mental health clinicians.
AB  - BACKGROUND: The majority of mental health clinicians report the use of homework
      to support their case management, but practitioner surveys indicate that homework
      is not routinely used. AIMS: To examine barriers that mental health case managers
      experience in implementing homework and to identify strategies to promote
      successful homework administration. METHOD: One hundred thirty-four surveys were
      completed by mental health case managers. The survey examined their use of
      homework for individuals diagnosed with a severe mental health problem. It also
      asked them to identify barriers to regularly implement homework and describe
      strategies to promote more regular use of homework. RESULTS: On average, homework
      was used at 50% of clinical contacts. The primary reasons for not using homework
      included allocating insufficient time at appointments, perceived client
      resistance for using homework and concerns that the client was too unwell.
      Strategies used to overcome these difficulties included prioritising the use of
      homework and ensuring that homework assignments were achievable. CONCLUSIONS:
      Clinicians are able to identify a range of practical strategies to promote the
      use of homework. Discussion focuses on the application of the suggested
      strategies to promote regular use of homework. This includes discussion of
      possible training approaches to enhance systematic homework administration.

PMID- 21942684
TI  - Antipsychotic-induced amenorrhea.
AB  - BACKGROUND: Many antipsychotic drugs used to treat schizophrenia can cause
      amenorrhea in a significant proportion of women. The overall impact of this side
      effect has been little studied. AIM: To review the literature on the meaning of
      menstruation to women. METHOD: This is a literature review of the meanings of
      menstruation to women in general, to women of different cultures, and to women
      with schizophrenia. RESULTS: Many women feel ambivalent with respect to
      menstruation. Its loss can produce difficulties for women suffering from
      schizophrenia, such as failure to use contraception, pseudocyesis, denial of
      pregnancy, erroneous perception of early menopause, or loss of the feeling of
      femininity. CONCLUSION: Attempts should be made to avoid the antipsychotic side
      effect of amenorrhea.

PMID- 21942677
TI  - Enzymes of the cyclooxygenase pathways of prostanoid biosynthesis.

PMID- 21942693
TI  - Relationship between reproductive aging, body composition, hormonal status and
      metabolic syndrome in postmenopausal women.
AB  - OBJECTIVE: To determine the relationship between different anthropometric
      indicators, reproductive aging and hormonal status in postmenopausal women with
      and without metabolic syndrome. METHODS: One hundred and forty non-surgical,
      postmenopausal women were enrolled to this cross-sectional study. Each
      participant completed a questionnaire and underwent a medical examination,
      including measurements of body mass index, weight and body composition criteria.
      Body composition was evaluated with measurements of the waist-to-hip
      circumference ratio and skinfold thickness (triceps, suprailiac and front thigh).
      Levels were determined of serum lipids, including cholesterol, high density
      lipoprotein cholesterol, low density lipoprotein cholesterol and triglycerides,
      and also fasting blood sugar, sex hormone binding globulin (SHBG), estradiol and
      testosterone. The metabolic syndrome was defined according to the definition of
      the National Cholesterol Education Program Adult Treatment Panel III. RESULTS:
      Logistic regression analysis revealed a significant association between weight (p
      < 0.001), age (p < 0.01) and SHBG (p = 0.021) with risk for metabolic syndrome.
      CONCLUSION: Age, SHBG and weight are critical correlates of metabolic syndrome in
      postmenopausal women.

PMID- 21942692
TI  - Virological response and resistance profiles after 24 months of first-line
      antiretroviral treatment in adults living in Bangui, Central African Republic.
AB  - The rate of virological failure was assessed in 386 adult patients attending the
      Centre National Hospitalier Universitaire of Bangui, the capital city of the
      Central African Republic (CAR), receiving their first-line antiretroviral (ARV)
      drug regimen for 24 months, according to the World Health Organization (WHO)
      recommendations. In addition, genotypic resistance testing was carried out in 45
      of 145 randomly selected patients whose plasma HIV-1 RNA load was detectable.
      Overall, 28.5% of ARV-treated patients were in virological failure (e.g., HIV-1
      RNA >3.7 log(10) copies/ml). Twenty-four percent of patients in virological
      failure showed wild-type viruses, likely indicating poor adherence. Even after
      excluding the M184V mutation, all 76% of patients in virological failure
      displayed viruses harboring at least one major drug resistance mutation to
      nucleoside reverse transcriptase inhibitors (NRTI), non-NRTI, or protease
      inhibitors. Whereas the second-line regimen proposed by the 2010 WHO
      recommendations, including zidovudine, tenofovir, lopinavir, and atazanavir,
      could be effective in more than 90% of patients in virological failure with
      resistant viruses, the remaining patients showed genotypic profiles highly
      predictive of resistance to the usual WHO second-line regimen, including complex
      genotypic profiles diagnosed only by genotypic resistance tests in some patients.
      In conclusion, our observations highlight the high frequency of therapeutic
      failure in ARV-treated adults in this study, as well as the urgent and absolute
      need for improving viral load assessment in the CAR to prevent and/or, from now
      on, to monitor therapeutic failure.

PMID- 21942694
TI  - Kinetics of liquid annulus formation and capillary forces.
AB  - The dependence of the capillary adhesion force F(cap) between a silica
      microsphere and a flat silica surface versus a time period t of the samples'
      contact (i.e., dwell-in time) is experimentally investigated using atomic force
      microscopy (AFM). F(cap) was found to be dependent on t if the humidity was >30
      35%. This dependence is exponential, with decay (characteristic) times of ~10 s.
      It is suggested that the kinetics of the adhesion process are related to the
      growth of the water annulus between surfaces. Furthermore, we propose that the
      growth kinetics has two components: (1) water vapor diffusion from the
      surrounding humid media into the gap between samples and (2) water drainage from
      the gap. The theory of diffusion through thin pores (i.e., gaps) is developed,
      and analytical formulas are obtained for the dependence of the meniscus radius r
      versus time t. However, the experimental dependence of F(cap) versus t and,
      consequently, r versus t obtained in this article disagrees with the theoretical
      prediction by several orders of magnitude. Similar results were obtained from the
      literature data for capillary forces between an AFM cantilever tip and a flat
      surface. Possible reasons for the deviation from diffusion theory are suggested:
      surface and Knudsen regimes of vapor diffusion, nonsteady state vapor flow, and
      tortuosity. Taking into account the viscous drainage of water from the multilayer
      gap can explain the experimental kinetics of bridge formation, but only if the
      viscosity of the adjacent multilayer of water is several orders of magnitude
      larger than the bulk viscosity.

PMID- 21942695
TI  - Behavioral problems, cognitive difficulties and quality of life in children with
      epilepsy: an analysis of parental concerns.
AB  - In cognitively impaired or young children with epilepsy, only proxy-report can be
      used for the assessment of Quality of Life (QOL) and behavior. The present study
      aims to propose proxy QOL tools applicable in all children with epilepsy and to
      examine the impact of epilepsy characteristics (e.g., age of onset of epilepsy,
      epilepsy syndrome) and child's age and situation (in mainstream school or in
      special institution). We studied 219 children with various types of epilepsy with
      and without cognitive impairment. The study adapted published QOL scales and used
      a new parental QOL questionnaire. Selected items concerned 6 "domains" of QOL:
      global QOL, illness impact, depression/anxiety, hyperactivity/disrupting
      behavior, sociability, and parental QOL. School situation, epilepsy syndrome, and
      age were significantly and differentially related to the QOL domains. The
      proposed QOL tools are applicable to all children with epilepsy independently of
      comorbid conditions and can be used in a clinical context and for research
      studies of QOL in children with epilepsy. Epilepsy syndromes in children and
      their associated factors have a crucial impact on parental concerns and QOL. 

PMID- 21942696
TI  - Speaking to the trained ear: musical expertise enhances the recognition of
      emotions in speech prosody.
AB  - Language and music are closely related in our minds. Does musical expertise
      enhance the recognition of emotions in speech prosody? Forty highly trained
      musicians were compared with 40 musically untrained adults (controls) in the
      recognition of emotional prosody. For purposes of generalization, the
      participants were from two age groups, young (18-30 years) and middle adulthood
      (40-60 years). They were presented with short sentences expressing six emotions
      anger, disgust, fear, happiness, sadness, surprise-and neutrality, by prosody
      alone. In each trial, they performed a forced-choice identification of the
      expressed emotion (reaction times, RTs, were collected) and an intensity
      judgment. General intelligence, cognitive control, and personality traits were
      also assessed. A robust effect of expertise was found: musicians were more
      accurate than controls, similarly across emotions and age groups. This effect
      cannot be attributed to socioeducational background, general cognitive or
      personality characteristics, because these did not differ between musicians and
      controls; perceived intensity and RTs were also similar in both groups.
      Furthermore, basic acoustic properties of the stimuli like fundamental frequency
      and duration were predictive of the participants' responses, and musicians and
      controls were similarly efficient in using them. Musical expertise was thus
      associated with cross-domain benefits to emotional prosody. These results
      indicate that emotional processing in music and in language engages shared
      resources.

PMID- 21942697
TI  - Emotional costs of inaccurate self-assessments: both self-effacement and self
      enhancement can lead to dejection.
AB  - Despite the popularity of the idea in American culture that self-enhancement
      confers psychological benefits, the evidence for this idea is mixed. In the
      present research, we tested the contention that overly positive self-assessments
      could lead to psychological distress. In two correlational studies (Studies 1 and
      2), we addressed some previous problems related to the measurement of self
      enhancement. By measuring self-enhancement through the discrepancy between self
      assessments of relative task performance and actual relative task performance, we
      found that self-enhancement, like self-effacement, was associated with greater
      vulnerability to depression. In two subsequent experiments (Studies 3 and 4), we
      found that leading low (or high) performers to perceive their performance as high
      (or low) through providing bogus performance feedback produced analogous effects
      on the magnitude of experienced dejection.

PMID- 21942698
TI  - Negating in order to be negative: the relationship between depressive rumination,
      message content and negation processing.
AB  - The current research explored the interaction between brooding, a maladaptive
      subtype of depressive rumination, and content valence, in a basic cognitive
      process of negation. Following presentation of positive and negative trait
      descriptions, phrased affirmatively or negatively (e.g., "Liz is/is not a smart
      person"), participants' associations were examined for congruency with the schema
      (e.g., "smart") or with its negation (e.g., "stupid"). We predicted that
      brooders' processing of negations would enhance the accessibility of negative
      content. Consistent with our prediction, brooders generated schema-congruent
      associations for negatively valenced schemas, but negation-congruent associations
      for positively valenced schemas, thus, maintaining negative content in both
      cases. In contrast, nonbrooders generated associations congruent with the
      negation regardless of schema valence. This processing pattern is suggestive of a
      possible pathway for negative content perseveration in rumination, and it attests
      to the context and person sensitivity of the negation process.

PMID- 21942699
TI  - Emotion perception is mediated by spatial frequency content.
AB  - Spatial frequencies have been shown to play an important role in face
      identification, but very few studies have investigated the role of spatial
      frequency content in identifying different emotions. In the present study we
      investigated the role of spatial frequency in identifying happy and sad facial
      expressions. Two experiments were conducted to investigate (a) the role of
      specific spatial frequency content in emotion identification, and (b)
      hemispherical asymmetry in emotion identification. Given the links between global
      processing, happy emotions, and low frequencies, we hypothesized that low spatial
      frequencies would be important for identifying the happy expression.
      Correspondingly, we also hypothesized that high spatial frequencies would be
      important in identifying the sad expression given the links between local
      processing, sad emotions, and high spatial frequencies. As expected we found that
      the identification of happy expression was dependent on low spatial frequencies
      and the identification of sad expression was dependent on high spatial
      frequencies. There was a hemispheric asymmetry with the identification of sad
      expression, especially in the right hemisphere, possibly mediated by high spatial
      frequency content. Results indicate the importance of spatial frequency content
      in the identification of happy and sad emotional expressions and point to the
      mechanisms involved in emotion identification.

PMID- 21942700
TI  - The cognitive and hedonic costs of dwelling on achievement-related negative
      experiences: implications for enduring happiness and unhappiness.
AB  - Increasing evidence suggests that multiple cognitive and motivational processes
      underlie individual differences in happiness (Lyubomirsky, 2001, 2008). One
      behavior that is associated with (un)happiness is self-reflection or dwelling. We
      hypothesized that unhappy individuals would be inclined to dwell about
      themselves, and that this behavior would have a variety of adverse consequences.
      Three studies tested the prediction that, unlike their happier peers, unhappy
      participants would be sensitive to unfavorable achievement feedback, likely to
      dwell about its implications and, hence, show impaired attention during important
      academic tasks. The results of Studies 1 and 2 showed that unhappy participants
      who had "failed" relative to peers subsequently displayed increased interfering
      thoughts; spent the most time performing a portion of the graduate record
      examination; and later demonstrated impaired reading comprehension. Study 3
      experimentally induced versus inhibiting dwelling and found that the manipulation
      only impacted unhappy students. Implications of our results for the consequences
      of dwelling for work and social functioning, as well as for detracting from
      enduring happiness, are discussed.

PMID- 21942701
TI  - Judgments of facial expressions of emotion in profile.
AB  - Despite the fact that facial expressions of emotion have signal value, there is
      surprisingly little research examining how that signal can be detected under
      various conditions, because most judgment studies utilize full-face, frontal
      views. We remedy this by obtaining judgments of frontal and profile views of the
      same expressions displayed by the same expressors. We predicted that recognition
      accuracy when viewing faces in profile would be lower than when judging the same
      faces from the front. Contrarily, there were no differences in recognition
      accuracy as a function of view, suggesting that emotions are judged equally well
      regardless of from what angle they are viewed.

PMID- 21942702
TI  - Temporal processing of emotional stimuli: the capture and release of attention by
      angry faces.
AB  - Neuroimaging data suggest that emotional information, especially threatening
      faces, automatically captures attention and receives rapid processing. While this
      is consistent with the majority of behavioral data, behavioral studies of the
      attentional blink (AB) additionally reveal that aversive emotional first target
      (T1) stimuli are associated with prolonged attentional engagement or "dwell"
      time. One explanation for this difference is that few AB studies have utilized
      manipulations of facial emotion as the T1. To address this, schematic faces
      varying in expression (neutral, angry, happy) served as the T1 in the current
      research. Results revealed that the blink associated with an angry T1 face was,
      primarily, of greater magnitude than that associated with either a neutral or
      happy T1 face, and also that initial recovery from this processing bias was
      faster following angry, compared with happy, T1 faces. The current data therefore
      provide important information regarding the time-course of attentional capture by
      angry faces: Angry faces are associated with both the rapid capture and rapid
      release of attention.

PMID- 21942703
TI  - Specificity of meta-emotion effects on moral decision-making.
AB  - A recently proposed dual process theory of moral decision-making posits that
      utilitarian reasoning (approving of harmful actions that maximize good
      consequences) is the result of cognitive control of emotion. This suggests that
      deficits in emotional awareness will contribute to increased utilitarianism. The
      present study explored the relative contributions of the different facets of
      alexithymia and the closely related constructs of emotional intelligence and mood
      awareness to utilitarian decision making. Participants (N = 86) completed the
      Toronto Alexithymia Scale, Trait Meta Mood Scale, the Mood Awareness Scale, and a
      series of high-conflict, personal moral dilemmas validated by Greene et al.
      (2008). A brief neuropsychological battery was also administered to assess the
      possible confounds of verbal reasoning and abstract thinking ability. Principal
      components analysis revealed two latent factors-clarity of emotion and attention
      to emotion-which cut across all three meta-emotion instruments. Of these, low
      clarity of emotion-reflecting difficulty in reasoning thoughtfully about one's
      emotions-predicted utilitarian outcomes and provided unique variance beyond that
      of verbal and abstract reasoning abilities. Results are discussed in the context
      of individual differences in emotion regulation.

PMID- 21942705
TI  - Small-conductance Ca2+-activated K+ channels: form and function.
AB  - Small-conductance Ca(2+)-activated K(+) channels (SK channels) are widely
      expressed throughout the central nervous system. These channels are activated
      solely by increases in intracellular Ca(2+). SK channels are stable
      macromolecular complexes of the ion pore-forming subunits with calmodulin, which
      serves as the intrinsic Ca(2+) gating subunit, as well as with protein kinase CK2
      and protein phosphatase 2A, which modulate Ca(2+) sensitivity. Well-known for
      their roles in regulating somatic excitability in central neurons, SK channels
      are also expressed in the postsynaptic membrane of glutamatergic synapses, where
      their activation and regulated trafficking modulate synaptic transmission and the
      induction and expression of synaptic plasticity, thereby affecting learning and
      memory. In this review we discuss the molecular and functional properties of SK
      channels and their physiological roles in central neurons.

PMID- 21942706
TI  - Ultra-high-responsivity broadband detection of Si metal-semiconductor-metal
      Schottky photodetectors improved by ZnO nanorod arrays.
AB  - This study describes a strategy for developing ultra-high-responsivity broadband
      Si-based photodetectors (PDs) using ZnO nanorod arrays (NRAs). The ZnO NRAs grown
      by a low-temperature hydrothermal method with large growth area and high growth
      rate absorb the photons effectively in the UV region and provide refractive index
      matching between Si and air for the long-wavelength region, leading to 3 and 2
      orders of magnitude increase in the responsivity of Si metal-semiconductor-metal
      PDs in the UV and visible/NIR regions, respectively. Significantly enhanced
      performances agree with the theoretical analysis based on the finite-difference
      time-domain method. These results clearly demonstrate that Si PDs combined with
      ZnO NRAs hold high potential in next-generation broadband PDs.

PMID- 21942707
TI  - Freestanding ultrananocrystalline diamond films with homojunction insulating
      layer on conducting layer and their high electron field emission properties.
AB  - Freestanding ultrananocrystalline diamond (UNCD) films with homojunction
      insulating layer in situ grown on a conducting layer showed superior electron
      field emission (EFE) properties. The insulating layer of the films contains large
      dendrite type grains (400-600 nm in size), whereas the conducting layer contains
      nanosize equi-axed grains (5-20 nm in size) separated by grain boundaries of
      about 0.5-1 nm in width. The conducting layer possesses n-type (or semimetallic)
      conductivity of about 5.6 * 10(-3) (Omega cm)(-1), with sheet carrier
      concentration of about 1.4 * 10(12) cm(-2), which is ascribed to in situ doping
      of Li-species from LiNbO(3) substrates during growth of the films. The conducting
      layer intimately contacts the bottom electrodes (Cu-foil) by without forming the
      Schottky barrier, form homojunction with the insulating layer that facilitates
      injection of electrons into conduction band of diamond, and readily field emitted
      at low applied field. The EFE of freestanding UNCD films could be turned on at a
      low field of E(0) = 10.0 V/MUm, attaining EFE current density of 0.2 mA/cm(2) at
      an applied field of 18.0 V/MUm, which is superior to the EFE properties of UNCD
      films grown on Si substrates with the same chemical vapor deposition (CVD)
      process. Such an observation reveals the importance in the formation of
      homojunction on enhancing the EFE properties of materials. The large grain
      granular structure of the freestanding UNCD films is more robust against harsh
      environment and shows high potential toward diamond based electronic
      applications.

PMID- 21942704
TI  - Adenosine and hypoxia-inducible factor signaling in intestinal injury and
      recovery.
AB  - The gastrointestinal mucosa has proven to be an interesting tissue in which to
      investigate disease-related metabolism. In this review, we outline some of the
      evidence that implicates hypoxia-mediated adenosine signaling as an important
      signature within both healthy and diseased mucosa. Studies derived from cultured
      cell systems, animal models, and human patients have revealed that hypoxia is a
      significant component of the inflammatory microenvironment. These studies have
      revealed a prominent role for hypoxia-induced factor (HIF) and hypoxia signaling
      at several steps along the adenine nucleotide metabolism and adenosine receptor
      signaling pathways. Likewise, studies to date in animal models of intestinal
      inflammation have demonstrated an almost uniformly beneficial influence of HIF
      stabilization on disease outcomes. Ongoing studies to define potential
      similarities with and differences between innate and adaptive immune responses
      will continue to teach us important lessons about the complexity of the
      gastrointestinal tract. Such information has provided new insights into disease
      pathogenesis and, importantly, will provide insights into new therapeutic
      targets.

PMID- 21942712
TI  - Transferability of atomic multipoles in amino acids and peptides for various
      density partitions.
AB  - Multipole expansion of electron density distribution is an efficient tool for
      evaluating the energy of interactions in molecules. In as much as atoms in
      macromolecules such as peptides are modeled with certain types of atoms derived
      from small organic molecules, investigating transferability of atomic multipoles
      for various partitions of molecular electron density is an important issue. In
      this study, multipole moments up to hexadecapoles for types of atoms present in
      selected amino acids, as well as di- and tripeptides composed of these amino
      acids, are computed using three density partitions: Hansen-Coppens aspherical
      pseudoatoms formalism, Hirshfeld's stockholder partition, and Bader's atoms in
      molecules theory. Electron density of relevant molecules is derived in a
      procedure including molecular wave function ab initio calculation for isolated
      molecules in geometry from X-ray measurements, calculation of theoretical
      structure factors for molecules put in a pseudocubic cell, and multipole
      refinement as in crystallographic data processing and computation of multipoles.
      The results were compared to calculations of multipole moments in AIM and in
      stockholder density partitions obtained directly from molecular wave functions.
      The presented comparison does not point unambiguously to any particular influence
      of multipole refinement on moments obtained from these two partitions. The
      advantage of stockholder partitioning in terms of transferability of atomic
      multipoles is affirmed. AIM and pseudoatoms provide slightly less transferable
      multipoles of lower order. Higher rank of multipole expansion reveals a
      transferability improvement in the case of AIM and meaningful deterioration for
      pseudoatoms.

PMID- 21942708
TI  - Effects of a monophasic combined oral contraceptive containing nomegestrol
      acetate and 17beta-oestradiol in comparison to one containing levonorgestrel and
      ethinylestradiol on markers of endocrine function.
AB  - OBJECTIVES: To compare the effects of two monophasic combined oral
      contraceptives, containing either nomegestrol acetate/17beta-oestradiol
      (NOMAC/E2) or levonorgestrel/ ethinylestradiol (LNG/EE) on endocrine function,
      androgens, and sex hormone-binding globulin (SHBG). METHODS: Randomised, open
      label, multi-centre trial involving 121 healthy women, aged 18-50 years old.
      Participants received NOMAC/E2 (2.5 mg/1.5 mg) in a 24/4-day regimen (n=60) or
      LNG/EE (150 MUg/30 MUg) in a 21/7-day regimen (n=61) for six cycles. The primary
      outcome was the change from baseline to cycle 6 in markers of adrenal and thyroid
      function, androgens, and SHBG. RESULTS: Total cortisol, corticosteroid-binding
      globulin (CBG), and thyroxine-binding globulin (TBG) increased from baseline in
      both groups, with significantly greater increases in the LNG/EE group. No
      relevant changes from baseline or differences between the groups were observed
      for thyroid-stimulating hormone (TSH) and free thyroxine (T4). Androgens and
      androgen precursors decreased from baseline in both groups, with significantly
      greater decreases in the LNG/EE group (except for free testosterone). A greater
      increase in SHBG was observed with NOMAC/E2 than with LNG/EE. CONCLUSIONS:
      NOMAC/E2 has significantly less influence on markers of adrenal and thyroid
      function and androgens than LNG/EE. The clinical relevance of these findings
      requires further study.

PMID- 21942713
TI  - Bradykinin and des-Arg10-kallidin enhance the adhesion of polymorphonuclear
      leukocytes to extracellular matrix proteins and endothelial cells.
AB  - Bradykinin-related peptides (kinins) are well known to contribute to leukocyte
      recruitment to inflammatory foci; however, a role of these universal pro
      inflammatory mediators in the first step of this process, i.e. the leukocyte
      adhesion to endothelial cells, is not well understood. In this work we found that
      bradykinin and des-Arg10-kallidin enhance the adhesion of polymorphonuclear
      bloods cells (PMN) to fibrinogen and fibronectin. Also, the PMN adherence to
      endothelial cells of HMEC-1 line strongly increased after stimulation by kinins,
      particularly des-Arg10-kallidin, or when PMN were co-stimulated with bradykinin
      and interleukin-1beta. These effects were attenuated after PMN treatment with a
      specific inhibitor of carboxypeptidases, which convert kinins to their des-Arg
      metabolites. The kinin peptides were also able to change the Mac-1 integrin
      expression on the PMN surface. These results suggest a regulatory effect of
      kinins on leukocyte adhesion to endothelial wall, providing new aspects of the
      leukocyte infiltration into inflamed tissues.

PMID- 21942714
TI  - Carotenoids retention and in vitro iron bioavailability of traditional cowpea
      leaf dishes of rural Tanzania.
AB  - Food preparation methods play a role in micronutrient retention and ultimately
      intake. Analyses for carotenoids retention and in vitro iron bioavailability of
      five cowpea leaf dishes prepared according to the traditional methods of rural
      Tanzania were carried out. All the five dishes are commonly eaten as relishes for
      staple meals of maize or rice. Laboratory analyses were carried out at the
      Nutrition Laboratory of the World Vegetable Centre in Taiwan. Carotenoids were
      analysed by high-performance liquid chromatography while iron bioavailability was
      analysed by an in vitro method. Results showed that traditional cowpea leaf dish
      consisting of sunflower oil, onion, tomatoes and coconut milk cooked for 30 min
      had the highest retention of beta-carotene (40.83 +/- 7.00%) and lutein (34.60 +/
      3.30%) compared to other traditional recipes (p < 0.05). The highest iron
      bioavailability (10.04 +/- 0.49%) was observed in the traditional recipe which
      involved boiling fresh cowpea leaves for 15 min. Although recipe variation can
      affect carotenoids retention and iron bioavailability, simple practices such as
      reduced cooking time and avoiding direct sun drying also need to be promoted.

PMID- 21942715
TI  - Proteomic dissection of the von Hippel-Lindau (VHL) interactome.
AB  - The von Hippel-Lindau (VHL) tumor suppressor gene encodes a component of a
      ubiquitin ligase complex containing elongin B, elongin C, cullin 2, and Rbx1,
      which acts as a negative regulator of hypoxia inducible factor (HIF). VHL
      ubiquitinates and degrades the alpha subunits of HIF, and this is proposed to
      suppress tumorigenesis and tumor angiogenesis. Several lines of evidence also
      suggest important roles for HIF-independent VHL functions in the maintenance of
      primary cilium, extracellular matrix formation, and tumor suppression. We
      undertook a series of proteomic analyses to gain a comprehensive picture of the
      VHL-interacting proteins. We found that the ARF tumor suppressor interacts with
      VHL30, a longer VHL isoform, but not with VHL19, a shorter VHL isoform. ARF was
      found to release VHL30 from the E3 ligase complex, promoting the binding of VHL30
      to a protein arginine methyltransferase, PRMT3. Our analysis of the VHL19
      interactome also uncovered that VHL19 displays an affinity to collagens and their
      biosynthesis enzymes.

PMID- 21942717
TI  - Direct synthesis of polysubstituted aluminoisoxazoles and pyrazoles by a
      metalative cyclization.
AB  - Alumino-heteroles are obtained from simple precursors in a fully chemo- and
      regioselective manner by a metalative cyclization. The carbon-aluminum bond is
      still able to react further with several electrophiles, without the need of
      transmetalation. This synthetic route provides a novel entry to heterocyclic
      organoaluminum reagents as well as a straightforward access to 3,4,5
      trisubstituted isoxazoles and 1,3,4,5-tetrasubstituted pyrazoles.

PMID- 21942716
TI  - LC/DAD/ESI/MS method for the determination of imidacloprid, thiacloprid, and
      spinosad in olives and olive oil after field treatment.
AB  - The behavior in the field and the transfer from olives to olive oil during the
      technological process of imidacloprid, thiacloprid, and spinosad were studied.
      The extraction method used was effective in extracting the analytes of interest,
      and no interfering peaks were detected in the chromatogram. The residue levels
      found in olives after treatment were 0.14, 0.04, and 0.30 mg/kg for imidacloprid,
      thiacloprid, and spinosad, respectively, far below the maximum residue levels
      (MRLs) set for these insecticides in EU. At the preharvest interval (PHI), no
      residue was detected for imidacloprid and thiacloprid, while spinosad showed a
      residue level of 0.04 mg/kg. The study of the effect of the technological process
      on pesticide transfer in olive oil showed that these insecticides tend to remain
      in the olive cake. The LC/DAD/ESI/MS method showed good performance with adequate
      recoveries ranging from 80 to 119% and good method limits of quantitation (LOQs)
      and of determination (LODs). No matrix effect was detected.

PMID- 21942718
TI  - Lewis acid-promoted three-component reactions of propargylic alcohols with 2
      butynedioates and secondary amines.
AB  - We report herein a three-component reaction of propargylic alcohols with 2
      butynedioates and secondary amines, which furnished functionalized
      dihydroazepines. In the cases where benzylmethylamine and benzyl-i-propylamine
      were used as the secondary amine, the reaction afforded 2,5-dihydro-1H-pyrroles
      and 2,3-dihydro-1H-pyrroles, respectively, as the major product along with the
      desired dihydroazepines. The reaction mode depends on the electronic and steric
      effect of the substitutents on the secondary amines used. A tentative mechanism
      for this cascade process is postulated. The key intermediate is ascribed to 1,3,4
      pentatrien-1-amine, which is formed by trapping the in situ generating allenic
      carbocation with enamine. Because of the reactivity of 1,3,4-pentatrien-1-amine
      formed, different products were thus formed.

PMID- 21942719
TI  - p-Thiophenylalanine-induced DNA cleavage and religation activity of a modified
      vaccinia topoisomerase IB.
AB  - Vaccinia DNA topoisomerase IB is the smallest of the type IB topoisomerases.
      Because of its small size (314 amino acids) and target site specificity
      (5'(C/T)CCTTp(?) sites), it constitutes an excellent model for studying the
      interaction of type IB enzymes with duplex DNA. In this study, p
      thiophenylalanine was incorporated into the enzyme active site (position 274) by
      in vitro translation in the presence of a chemically misacylated tRNA. The
      modification, which resulted in replacement of the nucleophilic tyrosine OH group
      with SH, retained DNA topoisomerase activity and did not alter the DNA cleavage
      site. However, the modified topoisomerase effected relaxation of supercoiled
      plasmid DNA at a rate about 16-fold slower than the wild-type enzyme. The
      thiophenylalanine-induced DNA cleavage rate (k(cl) = 1 * 10(-4) s(-1)) was 30
      times lower than for the wild-type enzyme (k(cl) = 3 * 10(-3) s(-1)). In
      contrast, thiophenylalanine-induced DNA religation was faster than that of the
      wild-type enzyme. We propose that the change in kinetics reflects the difference
      in bond energies between the O-P and S-P bonds being formed and broken in the
      reactions catalyzed by the wild-type and modified enzymes. We also studied the
      effect of adding Mg(2+) and Mn(2+) to the wild-type and modified topoisomerases
      I. Divalent metal ions such as Mg(2+) and Mn(2+) increased DNA relaxation
      activity of the wild-type and modified enzymes. However, the pattern of increases
      failed to support the possibility that metal ion-heteroatom interaction is
      required for catalysis.

PMID- 21942720
TI  - The impact of malocclusion on adolescents' dissatisfaction with dental appearance
      and oral functions.
AB  - OBJECTIVE: To investigate the impact of malocclusion on adolescents'
      dissatisfaction with dental appearance and oral functions and to identify
      components of malocclusion that may contribute to these outcomes. MATERIALS AND
      METHODS: The sample comprised 704 secondary school adolescents aged 12 to 13
      years from Balneario Camboriu, Brazil. A trained and calibrated orthodontist
      examined the severity of malocclusion using the Dental Aesthetic Index (DAI). A
      pretested questionnaire was used to assess reported dental appearance, self
      perception of speech, and self-perception of masticatory function using a 5-point
      scale of oral health status. The outcomes of the present study were
      dissatisfaction with dental appearance and dissatisfaction with oral functions.
      Simple and multivariate logistic regression analysis was performed to explore the
      association between DAI and outcomes and to quantify the effect of DAI components
      on dissatisfaction with dental appearance. RESULTS: Each DAI unit increase led to
      a significant increase of 5% in the likelihood of dissatisfaction with dental
      appearance (OR: 1.05; 95% CI 1.01-1.08). DAI components that exerted influence on
      dissatisfaction with dental appearance were: missing teeth (P  =  .010), largest
      maxillary anterior irregularity >=3 mm (P  =  .013), and largest mandibular
      anterior irregularity >=2 mm (P  =  .008). There was no association between
      severity of malocclusion and dissatisfaction with oral functions. CONCLUSIONS:
      Severity of malocclusion interfered with satisfaction of dental appearance in
      this population. Missing teeth and anterior irregularity were identified as
      factors influencing this outcome.

PMID- 21942721
TI  - Retrognathic maxilla in "Habsburg jaw". Skeletofacial analysis of Joanna of
      Austria (1547-1578).
AB  - OBJECTIVE: To evaluate the dentoskeletal features of the "Habsburg jaw" by
      analyzing the skull of Joanna of Austria. MATERIALS AND METHODS: The skull, the
      panoramic radiograph, and the lateral cephalogram of Joanna of Austria were
      analyzed. The cephalometric values of Joanna were compared to cephalometric
      standards for adult female subjects. RESULTS: The analysis of the dentition on
      the dry skull and on the panoramic radiograph showed a generalized horizontal
      alveolar bone resorption with severe bone loss that was interpreted as a sign of
      severe periodontal disease with respect to the young age (31 years). The
      cephalometric analysis revealed the presence of a skeletal Class III disharmony
      associated with maxillary retrusion and normal sagittal position of the mandible.
      The maxilla exhibited a reduction in the sagittal dimension while the mandible
      presented with increased dimensions both in total mandibular length (Co-Gn) and
      in the mandibular body (Go-Gn). The skeletal open bite contributed to the lack of
      mandibular protrusion though in presence of increased mandibular sagittal
      dimensions. CONCLUSION: Joanna of Austria appeared to be affected by a peculiar
      type of "Habsburg jaw" as the Class III skeletal disharmony was due to a
      retrognathic maxilla rather than to a prognathic mandible.

PMID- 21942722
TI  - Hypertonic saline for treating raised intracranial pressure: literature review
      with meta-analysis.
AB  - OBJECT: Currently, mannitol is the recommended first choice for a hyperosmolar
      agent for use in patients with elevated intracranial pressure (ICP). Some authors
      have argued that hypertonic saline (HTS) might be a more effective agent;
      however, there is no consensus as to appropriate indications for use, the best
      concentration, and the best method of delivery. To answer these questions better,
      the authors performed a review of the literature regarding the use of HTS for ICP
      reduction. METHODS: A PubMed search was performed to locate all papers pertaining
      to HTS use. This search was then narrowed to locate only those clinical studies
      relating to the use of HTS for ICP reduction. RESULTS: A total of 36 articles
      were selected for review. Ten were prospective randomized controlled trials
      (RCTs), 1 was prospective and nonrandomized, 15 were prospective observational
      trials, and 10 were retrospective trials. The authors did not distinguish between
      retrospective observational studies and retrospective comparison trials.
      Prospective studies were considered observational if the effects of a treatment
      were evaluated over time but not compared with another treatment. CONCLUSIONS:
      The available data are limited by low patient numbers, limited RCTs, and
      inconsistent methods between studies. However, a greater part of the data suggest
      that HTS given as either a bolus or continuous infusion can be more effective
      than mannitol in reducing episodes of elevated ICP. A meta-analysis of 8
      prospective RCTs showed a higher rate of treatment failure or insufficiency with
      mannitol or normal saline versus HTS.

PMID- 21942723
TI  - Safety of early endovascular catheterization and intervention through
      extracranial-intracranial bypass grafts.
AB  - OBJECT: The goal of this study was to demonstrate feasibility and evaluate
      technical aspects of early endovascular access through extracranial-intracranial
      (EC-IC) bypass grafts. METHODS: Patients undergoing endovascular interventions
      through the graft in the acute postoperative period following EC-IC bypass are
      presented. Results, complications, and technical nuances are reviewed. RESULTS:
      Fourteen endovascular procedures were performed in 5 patients after EC-IC bypass
      for ruptured aneurysms in 4 patients and posterior circulation ischemia in 1
      patient. In 2 patients, a saphenous vein graft (SVG) was used to bypass the
      common carotid artery (CCA) to the middle cerebral artery (MCA). One patient
      underwent a superficial temporal artery (STA)-MCA bypass, and in 2 other patients
      the STA stump was connected to the intracranial circulation via an interposition
      SVG. The interval from surgery to endovascular intervention spanned 2-18 days;
      the indication was intracranial vasospasm in all patients. One case involved
      angioplasty of the proximal anastomosis on postoperative Day 14. All other
      interventions entailed proximal access through the bypass conduit for
      intraarterial infusion of vasodilators. Significant vasospasm of the STA itself
      was encountered in 2 patients during endovascular manipulation, and it was
      treated with intraarterial nitroglycerin. There were no cases of anastomotic
      disruption. CONCLUSIONS: Endovascular catheterization and intervention involving
      a recent EC-IC bypass is feasible. The main limitation in this series was
      catheter-induced vasospasm involving the STA. A vein graft may be the more
      appropriate option in patients with subarachnoid hemorrhage who may require
      subsequent endovascular intervention for vasospasm.

PMID- 21942724
TI  - Results after treatment of craniopharyngiomas: further experiences with 73
      patients since 1997.
AB  - OBJECT: The authors report surgical and endocrinological results of a series of
      73 cases of craniopharyngioma that they treated surgically since 1997 to
      demonstrate their change in treatment strategy and its effect on outcome compared
      with a previous series and results reported in the literature. METHODS: A total
      of 73 patients underwent surgery for craniopharyngiomas between May 1997 and
      January 2005. In patients with poor clinical or neuropsychological condition,
      even following pretreatment, only stereotactic cyst aspiration took place (8
      cases). In the remaining patients, gross-total resection (GTR) was intended and
      appeared to be possible. The most frequent approaches were subfrontal (27 cases)
      and transsphenoidal (26 cases); in some cases, a multistep approach was used. The
      rate of GTR, complications, and functional outcome (comparing pre- and
      postoperative endocrine and neuropsychological testing) were evaluated. The mean
      duration of follow-up was 25.2 months. RESULTS: Gross-total resection was
      achieved in 88.5% of cases in which a transsphenoidal approach was used and 79.5%
      of those in which a transcranial approach was used (85.2% of those in which a
      subfrontal approach was used and 72.7% of those in which a frontolateral approach
      was used). In the total series, GTR was achieved in 83.1% of cases (vs 49.3% in
      the authors' former series). The complication rate was 13.8% without any
      mortality. New endocrine deficits were observed more frequently in patients
      treated with transcranial approaches over the years (16.3%-66.7% vs 2.6%-50.0%)
      but were less frequent after transsphenoidal approaches (5.2%-19.2% vs 2.9%
      45.7%). CONCLUSIONS: Open surgery with intended total resection remains the
      treatment of choice in most patients. Initial stereotactic cyst aspiration or
      medical pretreatment to improve the patients' condition and adequate choice of
      surgical approach(es) are essential to achieve that goal. Nevertheless, a
      moderate increase in endocrinological deficits has to be accepted. The authors
      recommend using radiotherapy only in cases in which there are tumor remnants or
      disease progression after surgery.

PMID- 21942725
TI  - Impact of admission month and hospital teaching status on outcomes in
      subarachnoid hemorrhage: evidence against the July effect.
AB  - OBJECT: The authors sought to identify the presence of a "July effect," a
      transient increase in adverse outcomes during July, among a cohort of spontaneous
      subarachnoid hemorrhage (SAH) admissions recorded in the National Inpatient
      Sample (NIS). METHODS: The discharge status, admission month, patient
      demographics, treatment parameters, and hospital characteristics among
      spontaneous SAH admissions were extracted from the 2001-2008 NIS. Multivariate
      regression was used to determine whether an unfavorable discharge status and/or
      in-hospital mortality significantly increased in summer months in a pattern
      suggestive of a July effect. Additional models were generated to assess the
      impact of hospital teaching status on these outcomes. RESULTS: Among 57,663,486
      hospital admissions from the 2001-2008 NIS, 52,879 cases of spontaneous SAH (ICD
      9-CM 430) were treated at teaching (36,914 cases [70%]) and nonteaching (15,965
      cases [30%]) facilities. Regression models failed to reveal a July effect for in
      hospital mortality (chi(2) = 0.75, p = 1.000) or unfavorable discharges (chi(2) =
      1.69, p = 0.999) among monthly SAH admissions, although they did suggest a
      significant reduction in these outcomes (in-hospital mortality, OR = 0.89, p <
      0.001; unfavorable discharges, OR = 0.88, p < 0.001) among teaching hospitals as
      compared with nonteaching hospitals after adjustment for disparities in
      demographic, treatment, and hospital characteristics. CONCLUSIONS: The discharge
      disposition among SAH admissions within the NIS was not suggestive of a July
      effect but did reveal that teaching institutions have significantly lower rates
      of adverse outcomes when compared with nonteaching hospitals. Note, however, that
      the origins of this difference related to teaching status remain unclear.

PMID- 21942726
TI  - Hypertonic saline.

PMID- 21942727
TI  - Glioblastoma therapy in the elderly and the importance of the extent of resection
      regardless of age.
AB  - OBJECT: The objective of this study was to analyze whether age influences the
      outcome of patients with glioblastoma and whether elderly patients with
      glioblastoma can tolerate the same aggressive treatment as younger patients.
      METHODS: Data from 361 consecutive patients with newly diagnosed cerebral
      glioblastoma (2000-2006) who underwent regular follow-up evaluation from initial
      diagnosis until death were prospectively entered into a database. Patients
      underwent resection (complete, subtotal, or partial) or biopsy, depending on
      tumor size, location, and Karnofsky Performance Scale score. Following surgery,
      all patients underwent adjuvant treatment consisting of radiotherapy,
      chemotherapy, or combined treatment. Patients older than 65 years of age were
      defined as elderly (146 total). RESULTS: Two hundred thirty-four patients
      underwent tumor resection (complete 26%, subtotal 29%, and partial 45%). One
      hundred twenty-seven underwent biopsy. Mean patient age was 61 years, and overall
      survival was 11.6 +/- 12.1 months. The overall survival of elderly patients (9.1
      +/- 11.6 months) was significantly lower than that of younger patients (14.9 +/-
      16.7 months; p = 0.0001). Stratifying between resection or biopsy, age was a
      negative prognostic factor in patients undergoing biopsy (4.0 +/- 7.1 vs 7.9 +/-
      8.7 months; p = 0.007), but not in patients undergoing tumor resection (13.0 +/-
      8.5 vs 13.3 +/- 14.5 months; p = 0.86). Survival of elderly patients undergoing
      complete tumor resection was 17.7 +/- 8.1 months. CONCLUSIONS: In this series of
      patients with glioblastoma, age was a prognostic factor in patients undergoing
      biopsy, but not in patients undergoing resection. Tumor location and patient
      clinical status may prohibit extensive resection, but resection should not be
      withheld from patients only on the basis of age. In elderly patients with
      glioblastoma, undergoing resection to the extent feasible, followed by adjuvant
      therapies, is warranted.

PMID- 21942728
TI  - Glioblastoma in the elderly.

PMID- 21942729
TI  - Direct control of electron transfer to the surface-CO bond on a Pt/TiO2 catalytic
      diode.
AB  - We study CO adsorption on a multilayer catalytic diode in which electron transfer
      at the metal-semiconductor (Pt/TiO(2)) junction is controlled by an applied
      external voltage. The multilayer diode structure enhances infrared absorption
      signals from CO molecules adsorbed on the small area Pt surface. We find that the
      diode behaves like a Schottky junction and that changes in electron transfer at
      the junction are directly correlated with reversible shifts in the vibrational
      frequency of adsorbed CO. Infrared polarization and incidence angle dependent
      studies show that the magnitude of vibrational frequency shift varies with
      orientation of the molecules being probed and increases with proximity to the
      Pt/TiO(2) interface. The results demonstrate the ability to control the metal
      adsorbate bond through external electronic modifications of a metal-support
      junction. The catalytic diode can potentially provide control of the surface
      chemical bond by an external voltage, providing a new approach for investigations
      in heterogeneous catalysis, sensors, and plasmonic devices.

PMID- 21942730
TI  - Letters to the editor.

PMID- 21942731
TI  - Response to: the problem with peptide presumption and low Mascot scoring.
AB  - A letter published in January 2011, "The Problem with Peptide Presumption and Low
      Mascot Scoring", raised concerns about the reporting of peptide identifications
      based on mass spectrometry data with high precursor mass accuracy. We explain why
      we believe these concerns are unfounded.

PMID- 21942732
TI  - The role of rain in dispersal of the primary inoculum of Plasmopara viticola.
AB  - Although primary infection of grapevines by Plasmopara viticola requires splash
      dispersal of inoculum from soil to leaves, little is known about the role of rain
      in primary inoculum dispersal. Distribution of rain splashes from soil to
      grapevine canopy was evaluated over 20 rain periods (0.2 to 64.2 mm of rain) with
      splash samplers placed within the canopy. Samplers at 40, 80, and 140 cm above
      the soil caught 4.4, 0.03, and 0.003 drops/cm(2) of sampler area, respectively.
      Drops caught at 40 and 80 cm (1.5 cm in diameter) were larger than drops at 140
      cm (1.3 cm). Leaf coverage by splashed drops, total drop number, and drop size
      increased with an increase in the maximum intensity of rain (mm/h) during any
      rain period. Any rainfall led to infection in potted grapevines placed outside on
      leaf litter containing oospores, if the litter contained germinated oospores at
      the time of rain; infection severity was unrelated to rain amount or intensity.
      Results from vineyards also indicate that any rain can carry P. viticola inoculum
      from soil to leaves and should be considered a splash event in disease prediction
      systems. Sampling for early disease detection should focus on the lower canopy,
      where the probability of splash impact is greatest.

PMID- 21942733
TI  - A rapid, sensitive, and cost-efficient assay to estimate viability of potato cyst
      nematodes.
AB  - Potato cyst nematodes (PCNs) are quarantine organisms, and they belong to the
      economically most relevant pathogens of potato worldwide. Methodologies to assess
      the viability of their cysts, which can contain 200 to 500 eggs protected by the
      hardened cuticle of a dead female, are either time and labor intensive or lack
      robustness. We present a robust and cost-efficient viability assay based on loss
      of membrane integrity upon death. This assay uses trehalose, a disaccharide
      present at a high concentration in the perivitelline fluid of PCN eggs, as a
      viability marker. Although this assay can detect a single viable egg, the limit
      of detection for regular field samples was higher, ~10 viable eggs, due to
      background signals produced by other soil components. On the basis of 30
      nonviable PCN samples from The Netherlands, a threshold level was defined
      (DeltaA(trehalose) = 0.0094) below which the presence of >10 viable eggs is
      highly unlikely (true for ~99.7% of the observations). This assay can easily be
      combined with a subsequent DNA-based species determination. The presence of
      trehalose is a general phenomenon among cyst nematodes; therefore, this method
      can probably be used for (for example) soybean, sugar beet, and cereal cyst
      nematodes as well.

PMID- 21942735
TI  - Quantum molecular dynamics of the topological properties of the electron density:
      charge transfer in H3(+) and LiF.
AB  - This paper presents a method to analyze the time evolution of electron density
      descriptors defined by the quantum theory of atoms in molecules. The wave packet
      nuclear dynamics was followed solving the time-dependent Schrodinger equation.
      The time evolution of the nuclear wave packets was combined with the electronic
      wave functions to follow the time dependence of the average values of topological
      electron density descriptors. The method was applied to the reactive collision of
      H(+) + H(2) under different initial conditions and the photodissociation of LiF
      for either diabatic or adiabatic processes, with emphasis on the information
      provided by the time evolution of the atomic charges. These examples illustrate
      how this approach allows for a detailed analysis of the electronic structure in
      the time domain.

PMID- 21942734
TI  - Stimulus modality and working memory performance in Greek children with reading
      disabilities: additional evidence for the pictorial superiority hypothesis.
AB  - This study investigated the effects of stimulus presentation modality on working
      memory performance in children with reading disabilities (RD) and in typically
      developing children (TDC), all native speakers of Greek. It was hypothesized that
      the visual presentation of common objects would result in improved learning and
      recall performance as compared to the auditory presentation of stimuli. Twenty
      children, ages 10-12, diagnosed with RD were matched to 20 TDC age peers. The
      experimental tasks implemented a multitrial verbal learning paradigm
      incorporating three modalities: auditory, visual, and auditory plus visual.
      Significant group differences were noted on language, verbal and nonverbal
      memory, and measures of executive abilities. A mixed-model MANOVA indicated that
      children with RD had a slower learning curve and recalled fewer words than TDC
      across experimental modalities. Both groups of participants benefited from the
      visual presentation of objects; however, children with RD showed the greatest
      gains during this condition. In conclusion, working memory for common verbal
      items is impaired in children with RD; however, performance can be facilitated,
      and learning efficiency maximized, when information is presented visually. The
      results provide further evidence for the pictorial superiority hypothesis and the
      theory that pictorial presentation of verbal stimuli is adequate for dual coding.

PMID- 21942736
TI  - Stress and phase purity analyses of diamond films deposited through laser
      assisted combustion synthesis.
AB  - Diamond films were deposited on silicon and tungsten carbide substrates in open
      air through laser-assisted combustion synthesis. Laser-induced resonant
      excitation of ethylene molecules was achieved in the combustion process to
      promote diamond growth rate. In addition to microstructure study by scanning
      electron microscopy, Raman spectroscopy was used to analyze the phase purity and
      residual stress of the diamond films. High-purity diamond films were obtained
      through laser-assisted combustion synthesis. The levels of residual stress were
      in agreement with corresponding thermal expansion coefficients of diamond,
      silicon, and tungsten carbide. Diamond-film purity increases while residual
      stress decreases with an increasing film thickness. Diamond films deposited on
      silicon substrates exhibit higher purity and lower residual stress than those
      deposited on tungsten carbide substrates.

PMID- 21942740
TI  - Magnolol-loaded core-shell hydrogel nanoparticles: drug release, intracellular
      uptake, and controlled cytotoxicity for the inhibition of migration of vascular
      smooth muscle cells.
AB  - Encapsulation and release behavior of a water-insoluble drug, magnolol, using a
      core-shell polysaccharide-based nanoparticle, manipulating the cellular
      internalization and controlled cytotoxic effect of magnolol-loaded nanoparticles
      over the A10 vascular smooth muscle cells (VSMCs) was reported. A magnolol
      polyvinylpyrrolidone (PVP) core phase was prepared, followed encapsulating by an
      amphiphilic carboxymethyl-hexanoyl chitosan (CHC) shell to form a magnolol-loaded
      core-shell hydrogel nanoparticles (termed magnolol-CHC nanoparticles). The
      resulting magnolol-CHC nanoparticles were employed for evaluation of drug release
      and controlled cytotoxic inhibition of VSMCs migration in vitro. A sustained
      release of the magnolol from the nanoparticles was determined. The magnolol-CHC
      nanoparticles exhibited outstanding cellular uptake efficiency, and under a
      cytotoxic evaluation, an increased antiproliferative effect and effective
      inhibition of VSMC migration as a result of efficient intracellular delivery of
      the encapsulated magnolol in comparison to free magnolol was achieved. We then
      envision a potential intracellular medication strategy with improved biological
      and therapeutic efficacy using the magnolol-CHC nanoparticles illustrated in this
      work.

PMID- 21942741
TI  - Antiulcer activity of anthocyanins from Rubus coreanus via association with
      regulation of the activity of matrix metalloproteinase-2.
AB  - Anthocyanins were extracted from the fruits of Rubus coreanus. Whether their
      antioxidant properties and antiulcer activity in gastric ulceration have been
      accompanied by the activation of matrix metalloproteainse-2 (MMP-2) was
      investigated. To assess the effect of anthocyanins on gastric ulcer, the rats
      were administered with anthocyanins (20, 50, and 80 mg/kg of body weight) before
      treatment with naproxen (80 mg/kg of body weight) to induce gastric ulceration.
      Lipid peroxidation and the activities of radical scavenging enzymes such as
      catalase, superoxide dismutase, and glutathione peroxidase were determined. The
      MMP-2 level was tested by zymography and Western blot. Anthocyanins of R.
      coreanus exhibit possible antiulcer activity in acute ulcer in a rat model by
      preventing lipid peroxidation and a significant increase in the activities of
      antioxidant enzymes such as catalase, superoxide dismutase, and glutathione
      peroxidase. Also, anthocyanins induce activation of MMP-2 and attenuate the
      activity of the proinflammatory molecules, such as tumor necrosis factor-alpha
      and interleukin-1beta.

PMID- 21942742
TI  - Highly diastereoselective and general synthesis of primary beta-fluoroamines.
AB  - A short, high yielding protocol has been developed for the highly
      diastereoselective (dr >20:1) and general synthesis of primary beta-fluoroamines
      by the enantioselective alpha-fluorination of aldehydes, conversion into the N
      sulfinyl aldimine, nucleophilic addition of various organometallic species, and 1
      degrees  amine liberation.

PMID- 21942743
TI  - Assembly of colloidal nanoparticles directed by the microstructures of
      polycrystalline ice.
AB  - We show that the microstructures of polycrystalline ice can serve as a confining
      template for one-dimensional assembly of colloidal nanoparticles. Upon simply
      freezing an aqueous colloid, the nanoparticles are excluded from ice grains and
      form chains in the ice veins. The nanoparticle chains are transferable and can be
      strengthened by polymer encapsulation. After coating with polyaniline shells,
      simple sedimentation is used to remove large aggregates, enriching single-line
      chains of 40 nm gold nanoparticles with a total length of several micrometers.
      When gold nanorods were used, they formed one-dimensional aggregates with
      specific end-to-end conformation, indicating the confining effects of the
      nanoscale ice veins at the final stage of freezing. The unbranched and ultralong
      plasmonic chains are of importance for future study of plasmonic coupling and
      development of plasmonic waveguides.

PMID- 21942744
TI  - The inhibiting activity of areca inflorescence extracts on human low density
      lipoprotein oxidation induced by cupric ion.
AB  - The oxidative modification of human low density lipoprotein (LDL) plays a
      significant role in atherosclerosis. In this study, the inhibiting activity of
      areca inflorescence extracts (AIEs) on LDL oxidation was investigated by an in
      vitro study with Trolox as the standard antioxidant. The kinetics of LDL
      oxidation, thiobarbituric acid reactive substances assay, ferric-reducing
      antioxidant power assay and copper chelation assay were also evaluated to assess
      the antioxidant activities of AIEs, and the results revealed that AIEs could
      delay the lag time and inhibit the formation of malondialdehyde in the process of
      LDL peroxidation induced by Cu(2+). The boiled water extract displayed the
      highest antioxidant activity compared with the ambient water extract and ethanol
      extract. The total phenolic contents and phenolic components of AIEs were also
      measured by high performance liquid chromatography method. Epicatechin, gallic
      acid and coumalic acid were the primary phenolic acids in AIEs.

PMID- 21942745
TI  - Hydrogen abstraction by chlorine atom from amino acids: remarkable influence of
      polar effects on regioselectivity.
AB  - Quantum chemistry computations have been used to investigate hydrogen-atom
      abstraction by chlorine atom from protonated and N-acetylated amino acids. The
      results are consistent with the decreased reactivity at the backbone alpha-carbon
      and adjacent side-chain positions that is observed experimentally. The individual
      effects of NH(3)(+), COOH, and NHAc substituents have been examined and reveal
      important insights. The NH(3)(+) group in isolation is found to be deactivating
      at the alpha-position, while the acetamido group is activating. For the COOH
      group, polar effects lead to a contrathermodynamic deactivation of the
      thermodynamically most favorable alpha-abstraction. In the N-acetylamino acid,
      the alpha-position is deactivated by the combined inductive effect of the
      substituents and the presence of an early transition structure, again overriding
      the greater thermodynamic stability of the alpha-centered radical product.
      Deactivation of the alpha-, beta-, and gamma-positions results in a peculiar
      stability for amino acids and peptides and their derivatives with respect to
      radical degradation.

PMID- 21942746
TI  - Young people's recognition of mental disorders and beliefs about treatment and
      outcome: findings from an Australian national survey.
AB  - OBJECTIVE: The aim of the study was to carry out a national survey in order to
      assess young people's recognition and beliefs about treatment for depression,
      anxiety disorders and schizophrenia/psychosis. METHOD: In 2011, telephone
      interviews were carried out with 3021 Australians aged between 15 and 25 years.
      Participants were presented with a case vignette describing either depression,
      depression with suicidal thoughts, depression with alcohol misuse,
      psychosis/schizophrenia, social phobia or post-traumatic stress disorder (PTSD).
      Questions were asked about what was wrong with the person, help-seeking
      intentions and the likely helpfulness of a broad range of interventions. RESULTS:
      Rates of recognition of depression were relatively high, with almost 75% of
      respondents using the correct label. Rates of recognition for the psychosis
      (schizophrenia) and PTSD vignettes were similar, with around one third of
      respondents using the correct labels. Only 3% of respondents were able to
      correctly label social phobia. Intentions to seek help were highest for
      depression with suicidal thoughts and lowest for social phobia, with family
      members nominated the most likely sources of help across all vignettes.
      CONCLUSIONS: Most young people believe in the importance of seeking professional
      help and they have good recognition of depression. However, there is still
      potential for young people's mental health literacy to improve in the areas of
      recognition and treatment beliefs for all the mental disorders covered in this
      survey, particularly social phobia which has very low recognition rates and a
      lower perceived need for treatment.

PMID- 21942747
TI  - The association between depression and thyroid disorders in a regionally
      representative Canadian sample.
AB  - A subsample of six provinces (n = 67,621) from the 2005 Canadian Community Health
      Survey was used to determine the gender-specific prevalence of depression among
      those with and without thyroid disorders. Information was not available on the
      type of thyroid disorder. Logistic regression analyses were conducted to
      determine the odds and socio-demographic correlates of depression among those
      with and without thyroid disorders. Women had a significantly higher prevalence
      of thyroid disorders (9.3%) and depression (6.6%) than men (2.4% and 3.7%,
      respectively). Thyroid disorders were associated with 22% higher odds of
      depression in women after adjusting for socio-demographic factors, but no
      association was found in men. Among women with and without thyroid disorders,
      younger age, lower income, and limitations in Activities in Daily Living (ADL)
      were associated with higher odds of depression. Results suggest that women with
      thyroid disorders are more vulnerable to depression, and socio-demographic
      correlates of depression are similar among women with and without thyroid
      disorders.

PMID- 21942748
TI  - Nonspecific mechanisms that enhance well-being in health-promoting behaviors.
AB  - OBJECTIVE: We tested whether the nonspecific or placebo enhancement of well-being
      brought about by a health-promoting behavior was due to expectancy having an
      unmediated effect on outcome (response expectancy theory) or because expectancy
      was mediated through the behavioral and affective consequences of positively
      valued goal satisfaction (motivational concordance theory). METHOD: Fifty-seven
      participants completed a breathing exercise (a simplified Buteyko technique)
      purporting to enhance well-being over a period of 4 days. Participants were
      randomized to receive either easy or difficult task instructions. Expectancy was
      measured at baseline and perceived effort (as an indicator of motivation) and
      adherence were measured at follow-up. Well-being was measured by perceived change
      in well-being at follow-up and by change in the Positive and Negative Affect
      Scale between baseline and follow-up. RESULTS: Expectancy (r = .42), adherence (r
      = .57), and effort (r = .90) correlated with perceived benefit. Multiple
      regression and mediation analysis showed that effort predicted (p < .01) well
      being independently of expectancy for all 3 measures of well-being, and that
      where expectancy predicted outcome, its effect was mediated by effort. Adherence
      failed to predict additional variance to outcome compared with effort and
      expectancy. CONCLUSION: These results are consistent with the hypothesis that
      placebo effects in therapeutic contexts are mediated via the affective
      consequences of performing a motivated ritual.

PMID- 21942749
TI  - Dynamic effects of craving and negative affect on adolescent smoking relapse.
AB  - OBJECTIVE: This study examined dynamic effects of daily variations in craving and
      negative affect on the next-day risk of the first lapse and relapse among 149
      adolescent daily smokers who achieved at least 24 hr of abstinence. METHOD:
      Participants completed real-time assessments of their smoking, craving, and
      negative affect 3 times per day during the 3 weeks after their quit attempt. The
      main outcome measures included the first lapse and relapse after at least 24 hr
      of abstinence from smoking. RESULTS: Cox regression analyses with time-varying
      covariates showed that daily increases in craving predicted the risk of lapsing
      and relapsing on the following day, even after accounting for concurrent smoking
      and baseline levels of craving and nicotine dependence. Day-to-day variations in
      negative affect did not predict time to first lapse or relapse. Individual
      differences in baseline craving, nicotine dependence, and depressive symptoms
      also did not predict the first lapse or relapse. CONCLUSIONS: The findings
      challenge the significance of adolescents' negative affect during cessation and
      emphasize the need to assess dynamic effects of craving in addition to baseline
      ratings of craving and nicotine dependence, as the latter may not be sufficient
      to explain adolescent smoking cessation outcomes.

PMID- 21942750
TI  - Posttraumatic stress symptoms in parents of children with cancer within six
      months of diagnosis.
AB  - OBJECTIVE: To investigate levels and correlates of posttraumatic stress symptoms
      (PTSS) in mothers and fathers of children and youth with cancer. METHODS: Mothers
      (n = 191) and fathers (n = 95), representing 195 families of children and youth
      with cancer, completed measures of PTSS (Impact of Event Scale-Revised),
      depression (Beck Depression Inventory-II), and anxiety (Beck Anxiety Inventory)
      between 2 and 22 weeks after their child's cancer diagnosis or recurrence of
      initial diagnosis. RESULTS: Substantial subgroups of mothers (41%) and fathers
      (30%) reported levels of PTSS that exceeded cut-offs for elevated symptoms, and
      these subgroups of parents were characterized by heightened symptoms of
      depression and anxiety. Fathers of children and youth treated for relapse
      reported higher rates of elevated PTSS than fathers of children and youth treated
      for first-time diagnosis, but mothers' rates were similar. Mothers and fathers
      reported comparable mean levels of PTSS that were strongly positively correlated
      with symptoms of anxiety and depression. PTSS and other symptoms of distress were
      negatively related to education level for fathers. CONCLUSION: These findings
      provide additional evidence that mothers and fathers experience substantial PTSS
      near the time of their child or adolescent's cancer diagnosis during the first 6
      months of treatment. Results suggest that PTSS may be part of a broader pattern
      of emotional distress and that a substantial portion of both mothers and fathers
      of children and youth with cancer may be in need of supportive mental health
      services within the first 6 months of their child's diagnosis.

PMID- 21942751
TI  - Spectroscopic characterization of the metal-binding sites in the periplasmic
      metal-sensor domain of CnrX from Cupriavidus metallidurans CH34.
AB  - CnrX, the dimeric metal sensor of the three-protein transmembrane signal
      transduction complex CnrYXH of Cupriavidus metallidurans CH34, contains one metal
      binding site per monomer. Both Ni and Co elicit a biological response and bind
      the protein in a 3N2O1S coordination sphere with a nearly identical octahedral
      geometry as shown by the X-ray structure of CnrXs, the soluble domain of CnrX.
      However, in solution CnrXs is titrated by 4 Co-equiv and exhibits an unexpected
      intense band at 384 nm that was detected neither by single-crystal spectroscopy
      nor under anaerobiosis. The data from a combination of spectroscopic techniques
      (spectrophotometry, electron paramagnetic resonance, X-ray absorption
      spectroscopy) showed that two sites correspond to those identified by
      crystallography. The two extra binding sites accommodate Co(II) in an octahedral
      geometry in the absence of oxygen and are occupied in air by a mixture of low
      spin Co(II) as well as EPR-silent Co(III). These extra sites, located at the N
      terminus of the protein, are believed to participate to the formation of peroxo
      bridged dimers. Accordingly, we hypothesize that the intense band at 384 nm
      relies on the formation of a binuclear MU-peroxo Co(III) complex. These metal
      binding sites are not physiologically relevant since they are not detected in
      full-length NccX, the closest homologue of CnrX. X-ray absorption spectroscopy
      demonstrates that NccX stabilizes Co(II) in two-binding sites similar to those
      characterized by crystallography in its soluble counterpart. Nevertheless, the
      original spectroscopic properties of the extra Co-binding sites are of interest
      because they are susceptible to be detected in other Co-bound proteins.

PMID- 21942752
TI  - The concordance and correlation of measurements by multiple electrode and light
      transmittance aggregometries based on the pre-defined cutoffs of high and low on
      treatment platelet reactivity.
AB  - The consensus document suggested the definition of high on-treatment platelet
      reactivity (HPR) and future directions. Although multiple platelet function
      assays have developed based on different mechanisms, inter-assay concordance of
      HPR identification may be an important pressing need. This study was performed to
      correlate between the cutoffs of HPR suggested by multiple electrode (MEA) and
      light transmittance aggregometries (LTA). We enrolled 246 consecutive patients
      undergoing non-emergent percutaneous coronary intervention after dual
      antiplatelet therapy. On the basis of consensus document, the cutoffs of HPR to
      adenosine diphosphate (ADP) were defined as ADPtest  >= 47 U, and 5 and 20 uM ADP
      induced maximal platelet aggregation (MPA) >= 46% and 59%, respectively. In
      addition, the cutoff of low PR (LPR) for major bleeding was selected as ADPtest 
      <= 19 U. ADPtest showed moderate correlations with ADP-based LTA data (0.663 <= r
      <= 0.710). In the receiver-operating characteristics (ROC) curve analysis,
      ADPtest  >= 47 U was corresponded to 5 and 20 uM ADP-induced MPAs  >= 46.4% and
      >= 56.8%, respectively. Good agreements were observed between ADPtest >= 47 U,
      and 5 uM ADP-induced MPA >= 46% (kappa=0.537, 80.5% of concordance rate) and 20
      uM ADP-induced MPA >= 59% (kappa=0.564, 81.7% of concordance rate). In the ROC
      curve analysis for the cutoff of LPR (ADPtest <= 19 U), 5 and 20 uM ADP-induced
      MPAs <= 26.6% and <= 35.3%, respectively, were suggested as the hypothetical
      threshold for major bleeding. On the basis of consensus document, the cutoffs of
      MEA- and LTA-based HPR are well matched. However, the agreement of HPR between
      assays is moderate, which may implicate the limitation of risk stratification by
      platelet function testing.

PMID- 21942753
TI  - Increased mean platelet volume in primary Raynaud's phenomenon.
AB  - We hypothesized that mean platelet volume (MPV), a reliable marker of platelet
      activation, might be elevated in primary Raynaud's phenomenon (PRP) even if there
      was no thrombotic complication in our subjects. In this retrospective-cohort
      study, we examined the clinical value of MPV in 200 patients with PRP and 116
      clinical controls, and measured MPV and platelet P-selectin (CD62P) in all study
      participants. We also evaluated the effect of age, gender, and disease duration
      on these platelet activation markers in PRP. MPV and CD62 positivities were
      significantly (p<0.001) elevated in patients with PRP compared with controls.
      These differences retained when patients and controls were analyzed according to
      age, gender, and the disease duration. In logistic regression analysis, MPV (OR:
      15.8, 95% CI: 8.14-30.64, p<0.001) and CD62P (OR: 11.3, 95% CI: 4.85-26.12,
      p<0.001) were found to be independently associated with PRP. In conclusion,
      increased MPV is independently related to PRP, and its level was not influenced
      by age, gender, and the duration of PRP.

PMID- 21942754
TI  - Dietary supplementation with l-arginine partially counteracts serum metabonome
      induced by weaning stress in piglets.
AB  - Arginine plays an important role in preventing intestinal dysfunction and
      metabolic disorders caused by early weaning stress. However, little is known
      about how arginine mitigates early weaning stress. This study was conducted to
      evaluate the effects of weaning stress and dietary arginine supplementation on
      the metabonome in the serum of piglets using (1)H NMR spectroscopy in conjunction
      with multivariate data analysis. Thirty castrated male piglets aged 21 d were
      evenly divided into three groups and fed in three different regimes: sow-fed
      (SF), weaned with l-alanine supplementation (ALA), and weaned with arginine
      supplementation (ARG). We found that early weaning stress led to a significantly
      reduced bodyweight gain (15.6%) and that supplementation with arginine can
      improve growth rates in piglets by 5.6% (P < 0.05). The early weaning stress was
      associated with marked alterations in lipid and amino acid metabolisms and
      perturbations in population and/or activities of gut microorganisms, which were
      manifested in increased levels of organic acids, amino acids, and acetyl
      glycoproteins and reduced levels of choline metabolism and lipoproteins. Dietary
      supplementation with arginine could partially counteract the changes of
      metabolites induced by weaning stress, such as lipid and amino acid metabolisms.
      However, arginine was not able to restore disturbed gut microbiota. These results
      demonstrate the central role of arginine supplementation in regulating the
      metabolisms of weaned piglets.

PMID- 21942755
TI  - Bladder neck plication stitch: a novel technique during robot-assisted radical
      prostatectomy to improve recovery of urinary continence.
AB  - BACKGROUND AND PURPOSE: Efforts to improve postprostatectomy incontinence have
      led to many modifications in surgical technique. We present our experience with a
      novel technique to improve continence outcomes in patients who are undergoing
      robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS: A consecutive
      series of 159 patients after initiation of a bladder neck plication stitch was
      compared with the most recent group before the change. After completion of the
      vesicourethral anastomosis, a single suture was used to plicate the distal
      bladder neck. A structured questionnaire was used for follow-up. Continence
      criteria used were 1 pad per day for social continence and 0 pad per day for
      total continence. RESULTS: A total of 334 patients were included in the study:
      159 in the plication stitch group vs 175 in the control group. Average age was
      59.1 vs 59.6 years, average body mass index was 27.9 vs 28.3 kg/m(2), and average
      prostate volume was 58.1 vs 60.9 cc, respectively. The mean time to reach social
      continence was 3.63+/-3.01 vs 5.33+/-4.89 weeks (P=0.004), and total continence
      was 5.10+/-3.80 vs 8.49+/-6.32 weeks (P=0.002), respectively. Chance of total
      continence improved with the bladder plication stitch: Odds ratio of 1.95+/-0.72
      (P<0.001) at 1 month, 1.25+/-0.56 (P=0.113) at 3 months, and 2.07+/-0.66
      (P=0.005) at 12 months. There were no bladder neck contractures or other urinary
      complications noted in either group. CONCLUSIONS: The bladder plication stitch is
      a simple and effective technical modification for shortening the period of
      recovery of urinary continence in RARP patients. Randomized controlled trials are
      under way to further evaluate this technique.

PMID- 21942759
TI  - Under-reporting of alcohol and substance use versus other psychiatric symptoms in
      individuals living with HIV.
AB  - Substance use is known to negatively impact outcomes in patients living with HIV
      by decreasing adherence to and effectiveness of antiretroviral therapies. Alcohol
      and other drug abuse and dependence are widespread among HIV-positive
      individuals, though reported rates vary greatly by study, suggesting the
      possibility of under-reporting. The extent to which patients minimize symptoms
      and the factors that influence reporting remain to be determined. The present
      study sought to gauge the degree to which substance use is under-reported in a
      primary care HIV clinic by evaluating the influence of anonymity versus
      confidentiality of self-report on endorsement rates. Patients (n = 55) currently
      receiving medical treatment completed a confidential questionnaire assessing the
      presence of alcohol abuse, other drug misuse, and Generalized Anxiety Disorder
      (GAD). Another group of 55 patients completed a comparable survey, but did so
      anonymously. The two groups were similar in terms of demographic characteristics,
      but self-report of substance use differed depending on how symptoms were
      assessed, with anonymous questionnaires yielding significantly (p<0.05) higher
      rates, compared to confidential surveys. Under-reporting appeared specific to
      alcohol and substance use, with no statistically significant differences between
      anonymous and confidential surveys in the proportion of patients endorsing
      symptoms of GAD. The fact that the screener specifically designed to identify
      patients in need of further evaluation produced lower rates of reported alcohol
      and drug use suggests that more work is needed to identify appropriate tools for
      accurately assessing substance use in HIV-positive patients so that adequate
      referrals and services can be offered to those in need.

PMID- 21942760
TI  - Exploiting biological activities of brown seaweed Ecklonia cava for potential
      industrial applications: a review.
AB  - Seaweeds are rich in vitamins, minerals, dietary fibres, proteins,
      polysaccharides and various functional polyphenols. Many researchers have focused
      on brown algae as a potential source of bioactive materials in the past few
      decades. Ecklonia cava is a brown seaweed that is abundant in the subtidal
      regions of Jeju Island in the Republic of Korea. This seaweed attracted extensive
      interest due to its multiple biological activities. E. cava has been identified
      as a potential producer of wide spectrum of natural substances such as
      carotenoids, fucoidans and phlorotannins showing different biological activities
      in vital industrial applications including pharmaceutical, nutraceutical,
      cosmeceutical and functional food. This review focuses on biological activities
      of the brown seaweed E. cava based on latest research results, including
      antioxidant, anticoagulative, antimicrobial, antihuman immunodeficiency virus,
      anti-inflammatory, immunomodulatory, antimutagenic, antitumour and anticancer
      effects. The facts summarized here may provide novel insights into the functions
      of E. cava and its derivatives and potentially enable their use as functional
      ingredients in potential industrial applications.

PMID- 21942761
TI  - Spatial interactions in the superior colliculus predict saccade behavior in a
      neural field model.
AB  - During natural vision, eye movements are dynamically controlled by the
      combinations of goal-related top-down (TD) and stimulus-related bottom-up (BU)
      neural signals that map onto objects or locations of interest in the visual
      world. In primates, both BU and TD signals converge in many areas of the brain,
      including the intermediate layers of the superior colliculus (SCi), a midbrain
      structure that contains a retinotopically coded map for saccades. How TD and BU
      signals combine or interact within the SCi map to influence saccades remains
      poorly understood and actively debated. It has been proposed that winner-take-all
      competition between these signals occurs dynamically within this map to determine
      the next location for gaze. Here, we examine how TD and BU signals interact
      spatially within an artificial two-dimensional dynamic winner-take-all neural
      field model of the SCi to influence saccadic RT (SRT). We measured point images
      (spatially organized population activity on the SC map) physiologically to inform
      the TD and BU model parameters. In this model, TD and BU signals interacted
      nonlinearly within the SCi map to influence SRT via changes to the (1) spatial
      size or extent of individual signals, (2) peak magnitude of individual signals,
      (3) total number of competing signals, and (4) the total spatial separation
      between signals in the visual field. This model reproduced previous behavioral
      studies of TD and BU influences on SRT and accounted for multiple inconsistencies
      between them. This is achieved by demonstrating how, under different experimental
      conditions, the spatial interactions of TD and BU signals can lead to either
      increases or decreases in SRT. Our results suggest that dynamic winner-take-all
      modeling with local excitation and distal inhibition in two dimensions accurately
      reflects both the physiological activity within the SCi map and the behavioral
      changes in SRT that result from BU and TD manipulations.

PMID- 21942762
TI  - Medial PFC damage abolishes the self-reference effect.
AB  - Functional neuroimaging studies suggest that the medial PFC (mPFC) is a key
      component of a large-scale neural system supporting a variety of self-related
      processes. However, it remains unknown whether the mPFC is critical for such
      processes. In this study, we used a human lesion approach to examine this
      question. We administered a standard trait judgment paradigm [Kelley, W. M.,
      Macrae, C. N., Wyland, C. L., Caglar, S., Inati, S., & Heatherton, T. F. Finding
      the self? An event-related fMRI study. Journal of Cognitive Neuroscience, 14, 785
      794, 2002] to patients with focal brain damage to the mPFC. The self-reference
      effect (SRE), a memory advantage conferred by self-related processing, served as
      a measure of intact self-processing ability. We found that damage to the mPFC
      abolished the SRE. The results demonstrate that the mPFC is necessary for the SRE
      and suggest that this structure is important for self-referential processing and
      the neural representation of self.

PMID- 21942763
TI  - Absence of face-specific cortical activity in the complete absence of awareness:
      converging evidence from functional magnetic resonance imaging and event-related
      potentials.
AB  - In this study, we explored the neural correlates of perceptual awareness during a
      masked face detection task. To assess awareness more precisely than in previous
      studies, participants employed a 4-point scale to rate subjective visibility. An
      event-related fMRI and a high-density ERP study were carried out. Imaging data
      showed that conscious face detection was linked to activation of fusiform and
      occipital face areas. Frontal and parietal regions, including the pre-SMA,
      inferior frontal sulcus, anterior insula/frontal operculum, and intraparietal
      sulcus, also responded strongly when faces were consciously perceived. In
      contrast, no brain area showed face-selective activity when participants reported
      no impression of a face. ERP results showed that conscious face detection was
      associated with enhanced N170 and also with the presence of a second negativity
      around 300 msec and a slow positivity around 415 msec. Again, face-related
      activity was absent when faces were not consciously perceived. We suggest that,
      under conditions of backward masking, ventral stream and fronto-parietal regions
      show similar, strong links of face-related activity to conscious perception and
      stress the importance of a detailed assessment of awareness to examine activity
      related to unseen stimulus events.

PMID- 21942764
TI  - Lateral OFC activity predicts decision bias due to first impressions during
      ultimatum games.
AB  - Despite the prevalence and potentially harmful consequences of first impression
      bias during social decision-making, its precise neural underpinnings remain
      unclear. Here, on the basis of the fMRI study using ultimatum games, the authors
      show that the responders' decisions to accept or reject offers were significantly
      affected by facial trustworthiness of proposers. Analysis using a model-based
      fMRI method revealed that activity in the right lateral OFC (lOFC) of responders
      increased as a function of negative decision bias, indicating a greater
      likelihood of rejecting otherwise fair offers, possibly because of the facial
      trustworthiness of proposers. In addition, lOFC showed changes in functional
      connectivity strength with amygdala and insula as a function of decision bias,
      and individual differences in the strengths of connectivities between lOFC and
      bilateral insula were also found to predict the likelihood of responders to
      reject offers from untrustworthy-looking proposers. The present findings
      emphasize that the lOFC plays a pivotal role in integrating signals related to
      facial impression and creating signal biasing decisions during social
      interactions.

PMID- 21942765
TI  - Diarylheptanoids from the seeds of Alpinia katsumadai as heat shock factor 1
      inducers.
AB  - Seven new diarylheptanoids, (-)-(R)-4"-hydroxyyashabushiketol (1), (3S,5S)
      alpinikatin (2), katsumain C (3), 7-epi-katsumain C (4), ent-alpinnanin B (5),
      ent-alpinnanin A (6), and ent-calyxin H (8), were isolated from the EtOAc extract
      of the seeds of Alpinia katsumadai together with three known compounds,
      alpinnanin B (7), epicalyxin H (9), and calyxin H (10). Each isomer mixture of 3
      and 4, 5-7, and 8-10 was separated successfully by preparative HPLC using a
      chiral column. The three isomer mixtures (3 and 4, 5-7, 8-10) at 1 MUM increased
      expression of heat shock factor 1 (HSF1) with fold increases of 1.438, 1.190, and
      1.316, respectively, which was accompanied with increased expression of heat
      shock protein (HSP) 27 (1.403-, 1.250-, and 1.270-fold, respectively) and HSP70
      (1.373-, 1.313-, and 1.229-fold, respectively) without cellular cytotoxicity,
      suggesting a possible application of these compounds as HSP inducers. Celastrol
      was used as a positive control of HSP induction, producing fold increases of
      1.066 (HSF1), 1.216 (HSP27), and 1.371 (HSP70) at 1 MUM. Compounds 1 and 2 did
      not affect the induction of HSF1 protein.

PMID- 21942766
TI  - An efficient and general method for the Heck and Buchwald-Hartwig coupling
      reactions of aryl chlorides.
AB  - The beta-diketiminatophosphane Pd complex acted as a powerful catalyst for the
      Heck coupling of aryl chlorides with alkenes. Various aryl and heteroaryl
      chlorides were coupled efficiently under relatively mild conditions. Furthermore,
      this catalytic system also proved to be highly active in the Buchwald-Hartwig
      coupling of deactivated and sterically hindered aryl chlorides at room
      temperature.

PMID- 21942767
TI  - In vitro physicochemical properties, osteogenic activity, and immunocompatibility
      of calcium silicate-gelatin bone grafts for load-bearing applications.
AB  - The use of a composite made of natural polymer gelatin and bioactive calcium
      silicate resembling the morphology and properties of natural bone may provide a
      solution to the problem of ceramic brittleness for load-bearing applications. The
      in vitro bioactivity, degradability, osteogenic activity, and immunocompatibility
      of three types of calcium silicate-gelatin composite bone grafts were
      characterized. The osteogenic activity and immunocompatibility were evaluated by
      incubating the bone grafts with human dental pulp cells. After soaking in a
      simulated body fluid (SBF) for 1 day, all materials were covered with clusters of
      "bone-like" apatite spherulites. The control material without gelatin exhibited
      an insignificant change in strength, degradability, and porosity and a small
      weight loss of 6% after 180 days of soaking in the SBF solution. In contrast, the
      soaking time imposed in this study did have a statistically significant effect on
      compressive strength, porosity, and weight loss of the gelatin-containing
      composites. After 180 days of soaking, the composite with 10 wt % gelatin lost
      47% and 10% in compressive strength and weight, respectively, with a porosity of
      23%. However, the presence of gelatin promoted greater cell attachment and
      proliferation on the composite bone grafts. Pulp cells on the calcium silicate
      gelatin bone grafts expressed higher levels of osteocalcin, osteopontin, and bone
      sialoprotein. The inhibition of inducible nitric oxide synthase and interleukin-1
      expression and the activation of interleukin-10 were increased with increasing
      gelatin content. Overall, these findings provide evidence that composite bone
      grafts containing 10 wt % gelatin with a high initial strength were bioactive,
      nontoxic, and osteogenic and may be able to promote bone healing for load-bearing
      applications.

PMID- 21942768
TI  - Factors influencing diamine oxidase activity and gamma-aminobutyric acid content
      of fava bean (Vicia faba L.) during germination.
AB  - Factors (germination time, spectra, temperature, pH, and chemical inhibitors)
      influencing diamine oxidase (DAO, EC 1.4.3.6) activity and gamma-aminobutyric
      acid (GABA) content of fava bean (Vicia faba L.) during germination were
      investigated in this study. DAO activity significantly increased in germinating
      seeds but varied with different organs. The enzyme activity was higher in shoot
      than that in cotyledon, hypocotyl, and radicle. When seeds were germinated in the
      dark, DAO activity was 2.35-, 2.00-, 2.36-, 4.40-, and 1.67-fold of that under
      white, red, blue, green, and yellow spectra, respectively. The optimum
      germination temperature and pH value for increasing DAO activity were 30  degrees
      C and 3.0, respectively. The DAO activity was inhibited significantly by
      aminoguanidine and sodium ethylenediamine tetracetate, while it was activated by
      CuCl(2) and CaCl(2). Germinating at an appropriate temperature and pH, 30% of
      GABA formation was supplied by DAO. Calcium was related to the regulation of DAO
      activity and GABA accumulation.

PMID- 21942779
TI  - Probiotics in the treatment of depression: science or science fiction?

PMID- 21942780
TI  - Young people's stigmatizing attitudes towards people with mental disorders:
      findings from an Australian national survey.
AB  - OBJECTIVE: The aim of this study was to carry out a national survey in order to
      assess young people's stigmatizing attitudes towards people with depression,
      anxiety disorders and psychosis/schizophrenia. METHOD: In 2011, telephone
      interviews were carried out with 3021 Australians aged between 15 and 25 years.
      Participants were presented with a case vignette describing either depression,
      depression with suicidal thoughts, depression with alcohol misuse,
      psychosis/schizophrenia, social phobia or PTSD. Questions were asked about
      stigmatizing attitudes, including personal and perceived stigma and desire for
      social distance. RESULTS: Across all disorders, respondents were least likely to
      agree that they should avoid the person described in the vignette and most likely
      to endorse beliefs about unpredictability, particularly in the case of the
      psychosis/schizophrenia and depression with substance abuse vignettes. Social
      phobia was most likely to be seen as a sign of personal weakness or 'not a real
      medical illness'. Perception of stigma in others was greater than that reported
      by respondents themselves. Desire for social distance was greatest for the
      psychosis/schizophrenia vignette and lowest for PTSD. For each vignette,
      respondents were most unwilling to work on a project with the person described in
      the vignette, while desire for social distance was generally lowest for
      developing a close friendship. CONCLUSIONS: While young people associated all
      mental disorders with unpredictability, patterns of stigmatizing attitudes
      differed according to disorder, with notable differences between
      psychosis/schizophrenia and social phobia. Anti-stigma interventions should focus
      on individual disorders rather than on 'mental illness' in general and may need
      to address beliefs about unpredictability, social phobia as due to weakness of
      character and dangerousness in those with more severe disorders. Interventions
      should also focus on bringing beliefs about public perceptions in line with
      personal beliefs, as the latter are much less stigmatizing.

PMID- 21942781
TI  - Differences in perceptions of coronary disease among Hong Kong Chinese:
      implications for the societal readiness in disease prevention.
AB  - Perceptions of coronary heart disease (CHD) influence individual health behavior,
      which is central to preventing the disease. Not enough is known about the
      demographic differences in perceptions of CHD among Chinese communities. This
      study examined these differences in the perceived seriousness and risk of CHD
      among Hong Kong Chinese. A self-developed questionnaire was administered to a
      convenient sample (n = 236). Significant differences were identified in the
      perceived seriousness and risk of CHD between younger and older age groups (p <
      0.001) and groups with lower and higher education levels (p < 0.001), but not
      between genders (p > 0.05). Over 50% of participants expressed greater concern
      about infectious disease than about CHD, while two-thirds to over half of female,
      older, and less educated participants were more concerned about stroke. This
      study highlighted populations with lower levels of CHD perception that need
      increased public education. The findings have implications for the societal
      readiness to establishing ongoing public healthcare strategies to increase
      awareness of CHD.

PMID- 21942782
TI  - Sex influence on face recognition memory moderated by presentation duration and
      reencoding.
AB  - OBJECTIVE: It has been suggested that women have a better face recognition memory
      than men. Here we analyzed whether this advantage depends on a better encoding or
      consolidation of information and if the advantage is visible during short-term
      memory (STM), only, or whether it also remains evident in long-term memory (LTM).
      METHOD: We tested short- and long-term face recognition memory in 36 nonclinical
      participants (19 women). We varied the duration of item presentation (1, 5, and
      10 s), the time of testing (immediately after the study phase, 1 hr, and 24 hr
      later), and the possibility to reencode items (none, immediately after the study
      phase, after 1 hr). RESULTS: Women showed better overall face recognition memory
      than men (etap2 = .15, p < .05). We found this advantage, however, only with a
      longer duration of item presentation (interaction effect Sex * DURATION: etap2 =
      .16, p < .05). Women's advantage in face recognition was visible mainly if
      participants had the possibility to reencode faces during former test trials.
      CONCLUSIONS: Our results suggest women do not have a better face recognition
      memory than men per se, but may profit more than men from longer durations of
      presentation during encoding or the possibility for reencoding. Future research
      on sex differences in face recognition memory should explicate possible causes
      for the better encoding of face information in women.

PMID- 21942783
TI  - Environmentally persistent free radicals (EPFRs)-2. Are free hydroxyl radicals
      generated in aqueous solutions?
AB  - A chemical spin trap, 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), in conjunction
      with electron paramagnetic resonance (EPR) spectroscopy was employed to measure
      the production of hydroxyl radical (.OH) in aqueous suspensions of 5%
      Cu(II)O/silica (3.9% Cu) particles containing environmentally persistent free
      radicals (EPFRs) of 2-monochlorophenol (2-MCP). The results indicate: (1) a
      significant differences in accumulated DMPO-OH adducts between EPFR containing
      particles and non-EPFR control samples, (2) a strong correlation between the
      concentration of DMPO-OH adducts and EPFRs per gram of particles, and (3) a slow,
      constant growth of DMPO-OH concentration over a period of days in solution
      containing 50 MUg/mL EPFRs particles + DMPO (150 mM) + reagent balanced by 200
      MUL phosphate buffered (pH = 7.4) saline. However, failure to form secondary
      radicals using standard scavengers, such as ethanol, dimethylsulfoxide, sodium
      formate, and sodium azide, suggests free hydroxyl radicals may not have been
      generated in solution. This suggests surface-bound, rather than free, hydroxyl
      radicals were generated by a surface catalyzed-redox cycle involving both the
      EPFRs and Cu(II)O. Toxicological studies clearly indicate these bound free
      radicals promote various types of cardiovascular and pulmonary disease normally
      attributed to unbound free radicals; however, the exact chemical mechanism
      deserves further study in light of the implication of formation of bound, rather
      than free, hydroxyl radicals.

PMID- 21942784
TI  - SenseCam improves memory for recent events and quality of life in a patient with
      memory retrieval difficulties.
AB  - A wearable camera that takes pictures automatically, SenseCam, was used to
      generate images for rehearsal, promoting consolidation and retrieval of memories
      for significant events in a patient with memory retrieval deficits. SenseCam
      images of recent events were systematically reviewed over a 2-week period. Memory
      for these events was assessed throughout and longer-term recall was tested up to
      6 months later. A written diary control condition followed the same procedure.
      The SenseCam review procedure resulted in significantly more details of an event
      being recalled, with twice as many details recalled at 6 months follow up
      compared to the written diary method. Self-report measures suggested
      autobiographical recollection was triggered by the SenseCam condition but not by
      reviewing the written diary. Emotional and social wellbeing questionnaires
      indicated improved confidence and decreased anxiety as a result of memory
      rehearsal using SenseCam images. We propose that SenseCam images provide a
      powerful boost to autobiographical recall, with secondary benefits for quality of
      life.

PMID- 21942785
TI  - Delineation of folding pathways of a beta-sheet miniprotein.
AB  - Several methods have been developed in the past few years for the analysis of
      molecular dynamics simulations of biological (macro)molecules whose complexity is
      difficult to capture by simple projections of the free-energy surface onto one or
      two geometric variables. The locally scaled diffusion map (LSDMap) method is a
      nonlinear dimensionality reduction technique for describing the dynamics of
      complex systems in terms of a few collective coordinates. Here, we compare LSDMap
      to two previously developed approaches for the characterization of the
      configurational landscape associated with the folding dynamics of a three
      stranded antiparallel beta-sheet peptide, termed Beta3s. The analysis is aided by
      an improved procedure for extracting pathways from the equilibrium transition
      network, which enables calculation of pathway-specific cut-based free energy
      profiles. We find that the results from LSDMap are consistent with analysis based
      on transition networks and allow a coherent interpretation of metastable states
      and folding pathways in terms of different time scales of transitions between
      minima on the free energy projections.

PMID- 21942787
TI  - Effect of mechanical debridement on distal periodontal aspects of second molars
      after the extraction of third molars: a systematic review.
AB  - BACKGROUND: The risk of periodontal defects after the extraction of third molars
      continues to challenge clinicians. METHODS: Intervention trials, including
      subgingival scaling and/or root planing, were systematically reviewed. Data
      sources included the Cochrane Oral Health Group Trials Register and MEDLINE. The
      primary outcome was postoperative change in pocket probing depth (PD). RESULTS:
      The electronic search yielded 751 abstracts, and manual searching added one
      study. From them, four trials fulfilled the inclusion criteria and were selected
      for review. The overall sample size of the studies was small, ranging from 15 to
      30 participants. Only one trial was considered to present with low risk for bias
      in the sequence generation, the concealment of allocation to treatment, and the
      strategy for masking. The lack of information provided by the authors of the
      remaining studies resulted in unclear or high risk of bias for the chief
      dimensions of trial quality. The heterogeneity of the studies did not allow the
      use of meta-analysis to summarize the results of several studies. Preliminary
      evidence originating from a small study suggests that ultrasonic root debridement
      of the second molar and a three-visit plaque control program may have a
      beneficial effect on PD levels on the second molar. CONCLUSION: The available
      intervention trials on this topic have important limitations, and, consequently,
      there is insufficient evidence to recommend the use of mechanical debridement of
      second molars after the extraction of third molars.

PMID- 21942786
TI  - An extended beta7alpha7 substrate-binding loop is essential for efficient
      catalysis by 3-deoxy-D-manno-octulosonate 8-phosphate synthase.
AB  - The enzyme 3-deoxy-D-manno-octulosonate 8-phosphate (KDO8P) synthase catalyzes
      the reaction between phosphoenolpyruvate and arabinose 5-phosphate (A5P) in the
      first committed step in the biosynthetic pathway for the formation of 3-deoxy-D
      manno-octulosonate, an important component in the cell wall of Gram-negative
      bacteria. KDO8P synthase is evolutionarily related to the first enzyme of the
      shikimate pathway, 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAH7P) synthase,
      which uses erythrose 4-phosphate in place of A5P. The A5P binding site in KDO8P
      synthase is formed by three long loops that extend from the core catalytic
      (beta/alpha)(8) barrel, beta2alpha2, beta7alpha7, and beta8alpha8. The extended
      beta7alpha7 loop is always present in KDO8P synthase yet is not observed for
      DAH7P synthase. Modeling of this loop indicated interactions between this loop
      and the extended beta2alpha2 loop; both loops provide key hydrogen-bonding
      contacts with A5P. The two absolutely conserved residues on the beta7alpha7 loop
      (Gln and Ser) were mutated to Ala in both the metal-dependent KDO8P synthase from
      Acidithiobacillus ferrooxidans and the metal-independent KDO8P synthase from
      Neisseria meningitidis. In addition, mutants were constructed for both enzymes
      with the extended beta7alpha7 loop excised to match the DAH7P synthase
      architecture. Removal of the loop extension severely hindered efficient
      catalysis, dramatically increasing the K(m)(A5P) and reducing the k(cat) for both
      enzymes. Excision of the complete loop was far more detrimental to catalysis than
      the double mutations of the two conserved Gln and Ser residues. Therefore, the
      presence of the entire extended beta7alpha7 loop is important for efficient
      catalysis by KDO8P synthase, with the loop acting to promote efficient and
      productive binding of A5P.

PMID- 21942788
TI  - Salivary levels of antibacterial peptide (LL-37/hCAP-18) and cotinine in patients
      with chronic periodontitis.
AB  - BACKGROUND: The purpose of this study is to examine the relationship between
      salivary LL-37 levels and clinical severity in patients with chronic
      periodontitis (CP). The presence/absence of four periodontopathic bacteria and
      salivary cotinine levels were also examined to assess the impact of these factors
      on LL-37 production. METHODS: Unstimulated salivary samples were collected from
      69 patients with CP. Salivary concentrations of LL-37 and cotinine were measured
      by enzyme-linked immunosorbent assay. Aggregatibacter actinomycetemcomitans,
      Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola in saliva
      were detected by polymerase chain reaction. Periodontal examination included
      determination of probing depth (PD), clinical attachment level, bleeding on
      probing, and plaque control record. RESULTS: Mean salivary LL-37 concentration
      was 225.0 +/- 227.2 ng/mL, and a high prevalence of periodontopathic bacteria was
      observed. The stepwise ordinal logistic regression model showed that high
      salivary LL-37 levels were significantly associated with the presence of T.
      denticola and higher percentage of teeth with PD >=5 mm. In addition, higher
      salivary cotinine levels (>=8 ng/mL) were negatively associated with salivary LL
      37 levels. CONCLUSIONS: Salivary LL-37 level was positively correlated with
      severe periodontal destruction, and production was apparently associated with
      periodontopathic bacterial infection. The negative correlations between salivary
      LL-37 and cotinine levels also suggest that smoking or long-term exposure to
      environmental tobacco smoke can lead to lower LL-37 levels in the oral cavity and
      increased risk of periodontitis.

PMID- 21942789
TI  - Mesenchymal stem cells and their challenges for bone regeneration and
      osseointegration.
AB  - Bone regeneration is an indispensable procedure for implant placement. Original
      techniques based on mesenchymal stromal cell (MSC) therapy are emerging with the
      goal of speeding up biology, thereby reducing the osseointegration period. Many
      products found their way in clinical application, yet their reliability remains
      uncertain because many in vitro culture-related challenges are facing these cells
      once they are out of their biologic environment. In this commentary, these
      limitations are discussed with the emphasis of their impact on the performance of
      MSCs. Clinicians should be aware of these issues before implementing this cell
      based regenerative technique.

PMID- 21942790
TI  - Differential effects of amelogenin on mineralization of cementoblasts and
      periodontal ligament cells.
AB  - BACKGROUND: Amelogenin is a major component of developing extracellular enamel
      matrix proteins and plays a crucial role during the formation of tooth enamel. In
      addition, amelogenins are suggested to exert biologic functions as signaling
      molecules through cell-surface receptors. The purpose of this study is to examine
      the effect of recombinant human full-length amelogenin (rh174) on the
      mineralization of human cementoblasts (HCEMs) and human periodontal ligament
      cells (HPDLs). METHODS: HCEMs, namely, a cell line immortalized by transfection
      of human telomerase reverse transcription gene, and HPDLs isolated from human
      first premolars were cultured and treated with 0 to 1,000 ng/mL rh174. The
      messenger ribonucleic acid (mRNA) levels of alkaline phosphatase (ALP),
      osteocalcin (OCN), and bone sialoprotein (BSP) were examined by real-time
      polymerase chain reaction analysis. The protein levels of OCN and BSP were
      examined by Western blot analysis. ALP activity and calcium deposition of cell
      cultures were also determined. Mineralization of cells was evaluated by red dye
      staining. RESULTS: The treatment of HCEMs with rh174 upregulated the ALP, OCN,
      and BSP mRNA levels. In addition, the protein levels of OCN and BSP, ALP
      activity, and calcium deposition were enhanced, resulting in enhanced
      mineralization. Conversely, there were no significant effects of rh174 on the
      mineralization of HPDLs. CONCLUSION: The present study shows that rh174 enhances
      mineralization accompanied by upregulation of mineralization markers in HCEMs,
      whereas it has no effect on that in HPDLs, suggesting different effects of
      amelogenin on PDL and cementum.

PMID- 21942791
TI  - Ridge preservation with or without an osteoinductive allograft: a clinical,
      radiographic, micro-computed tomography, and histologic study evaluating
      dimensional changes and new bone formation of the alveolar ridge.
AB  - BACKGROUND: The aim of this randomized, controlled clinical trial is to determine
      whether ridge preservation using an osteoinductive allograft (test) would prevent
      ridge resorption and promote bone maturation compared to extraction alone
      (control). METHODS: Seventeen patients (20 total sites), in need of a non-molar
      extraction and delayed implant placement were randomly selected to receive either
      ridge preservation or extraction alone. A cone-beam computed tomography was
      completed with a radiographic stent in place before extraction and 10 to 12 weeks
      postoperatively for dimensional and buccal plate analyses. Bone cores were taken
      for micro-computed tomography (microCT) and histologic analyses. RESULTS:
      Resorption of the alveolar ridge occurred at all sites with no statistically
      significant differences found between test and control sites. A significant
      correlation was found between the initial buccal plate thickness and the loss of
      vertical ridge height. microCT and histologic analyses found a mean new bone
      volume of 44.9% with microCT and 37.4% with histology in test sites and 39% and
      35.5%, respectively, in control sites. The residual graft volume was 2.4% with
      microCT and 4.5% with histology. CONCLUSIONS: Test and control sites lost similar
      amounts of alveolar ridge, with the loss of buccolingual width occurring
      predominantly at the expense of the buccal bone. A thicker buccal plate was
      associated with less ridge loss in the vertical dimension. The percentage of new
      bone was not statistically significant between either the test or control sites,
      using either microCT or histologic analyses.

PMID- 21942792
TI  - Endoscopically assisted tunnel approach for minimally invasive corticotomies: a
      preliminary report.
AB  - BACKGROUND: The dental community has expressed low acceptance of traditional
      corticotomy techniques for corticotomy-facilitated orthodontics. These procedures
      are time consuming, entail substantial postoperative morbidity and periodontal
      risks, and are often perceived as highly invasive. METHODS: A total of 114
      interdental sites were treated in nine consecutive patients. Under local
      anesthesia, a tunnel approach requiring one to three vertical incisions per arch
      (depending on the targeted teeth) was used. Piezosurgical corticotomies and
      elective bone augmentation procedures were performed under endoscopic assistance.
      Postoperative cone-beam computerized tomography evaluation was used to confirm
      adequate corticotomy depth. RESULTS: Procedures were completed in a mean time of
      26 minutes. Follow-up evaluations revealed no loss of tooth vitality, no changes
      in periodontal probing depth, good preservation of the papillae, and no gingival
      recession. No evidence of crestal bone height reduction or apical root resorption
      was detected. CONCLUSIONS: The tunnel approach minimizes soft-tissue debridement
      and permits effective cortical cuts. The combination of piezosurgery technique
      with endoscopic assistance provides a quick, reliable means to design and perform
      these corticotomies while maximizing root integrity preservation. Moreover, the
      sites needing bone augmentation are selected under direct vision. Compared to
      traditional corticotomies, this procedure has manifest advantages in surgical
      time, technical complexity, patient morbidity, and periodontium preservation.

PMID- 21942796
TI  - Independent diagnostic and post-treatment prognostic models for prostate cancer
      demonstrate significant correlation with disease progression end points.
AB  - BACKGROUND AND PURPOSE: A major advance in the standard practice of tissue-based
      pathology is the new discipline of systems pathology (SP) that uses computational
      modeling to combine clinical, pathologic, and molecular measurements to predict
      biologic activity. Recently, a SP-based prostate cancer (PCa) predictive model
      for both preoperative (Px+) and postoperative (Px) prostatectomy has been
      developed. The purpose of this study is to calculate the percent agreement and
      the concordance between the Px+ and Px end points. PATIENTS AND METHODS: Fifty
      three patients underwent robot-assisted prostatectomy for PCa, and had Px+ and Px
      testing performed. Data were collected on Px+ end points and Px end points along
      with pathologic specimen results. The percent agreement and the degree of
      correlation between the Px+ and Px end points were then calculated. RESULTS: The
      percent agreement (PA) between Px+ end points and Px end points ranged from 77%
      to 87%. The PA between a high Px+ favorable pathology (FP) classification and
      dominant Gleason score <= 3 and Gleason sum <= 6 was 71.7% and 37.4%,
      respectively. On univariate analysis, Px+ disease progression (DP) score
      significantly correlated with Px prostate-specific antigen recurrence (PSAR)
      score (P<0.001), while Px+ DP probability significantly correlated with PxPSAR
      probability (P<0.001). Px+ FP probability significantly correlated with
      postprostatectomy dominant Gleason grade <= 3 (P<0.001) and Gleason sum
      (P<0.001). CONCLUSION: The PA between Px+ and Px testing end points for radical
      prostatectomy patients was very good. Furthermore, there was a direct correlation
      between most Px+ and Px end points. While the Px+FP classification and Gleason
      sum demonstrated a poor PA, Px+FP score still maintained a direct correlation to
      prostatectomy Gleason sum.

PMID- 21942797
TI  - Retroperitoneal laparoscopic kidney biopsy: technical tips for a minimally
      invasive approach.
AB  - OBJECTIVES: Nowadays, ultrasound-guided percutaneous kidney biopsy (PKB) is the
      gold standard for renal biopsies. Nevertheless, PKB is still contraindicated by
      conditions such as bleeding diatheses, severe obesity, solitary kidney,
      uncontrolled hypertension, and previous failed attempts at PKB. In these cases,
      the laparoscopic approach may offer a valid and mini-invasive alternative to open
      biopsy. We describe our technique and report indications and outcomes of a
      consecutive series of retroperitoneal laparoscopic kidney biopsies (LKB).
      MATERIALS AND METHODS: In a retrospective review of patients who underwent LKB,
      we examined indications, outcomes, and complications, stratified according to the
      Clavien classification. RESULTS: In all, 40 patients underwent LKB between 2001
      and 2010 (mean age 58.85 years, SD 10.87). Mean serum creatinine at surgery was
      3.02 mg/dL. Indications for LKB included coagulopathy (30%), polycystic kidney or
      multiple renal cysts (30%), solitary kidney (12.5%), and morbid obesity (10%).
      All the biopsies were performed with a Trucut needle. All the procedures were
      successful and led to pathological diagnosis. The most common pathological
      findings were glomerulonephritis (47.5%) and glomerulosclerosis (27.5%). All
      biopsies were performed in less than 1 hour. Only three complications (7.5%) were
      reported: two grade I and one grade IIIa according to Clavien classification. In
      three selected cases, we used a particular "ready-to-laparo" open surgical
      technique, which allowed to view a part of kidney parenchima through the 10-mm
      incision made for the Hasson trocar sufficient for Trucut biopsies and hemostasis
      under direct vision. CONCLUSIONS: This study shows that LKB is a safe, effective,
      and minimally invasive procedure that allows direct control of hemostasis and
      lower risks of postoperative morbidity compared with open biopsy. When PKB is
      contraindicated, LKB should be the first-choice alternative.

PMID- 21942798
TI  - A phantom model as a teaching modality for laparoscopic partial nephrectomy.
AB  - PURPOSE: To evaluate a materials model for laparoscopic ultrasound identification
      and partial nephrectomy of kidney tumors. METHODS: Five urology fellows performed
      laparoscopic ultrasonography (LUS) examination of the tumor model, and the time
      for identification was recorded. After identifying the tumor, they performed a
      laparoscopic partial nephrectomy using the target tumor with measurement of
      operative parameters. They completed a questionnaire and rated the quality of the
      renal tumor model on a 5-point Likert scale. RESULTS: The participants were able
      to identify 49 tumors by LUS (98%). The mean time to identify the renal tumors by
      LUS was 1.12 minutes +/- 0.93 standard deviation (SD). A partial nephrectomy was
      successfully completed on 49 tumor models (98%). The mean resection time was 7.69
      minutes +/- 3.8 SD. All of the participants considered that this model was
      helpful in the practice of LPN. The fellows would recommend this model as a
      teaching tool for residents/fellows to perform tumor imaging by LUS and for
      practicing LPN in a simulated environment. CONCLUSION: We have developed a unique
      model that simulates small kidney tumors that can be used for training surgeons
      in the clinical skills of laparoscopic partial nephrectomy.

PMID- 21942799
TI  - Impact of median lobe anatomy: does its presence affect surgical margin rates
      during robot-assisted laparoscopic prostatectomy?
AB  - PURPOSE: To measure and describe the impact of median lobe anatomy on surgical
      margin status after robot-assisted laparoscopic prostatectomy (RALP). PATIENTS
      AND METHODS: We prospectively collected median lobe status, surgical margin
      status, and other perioperative data on 791 patients who underwent RALP at our
      institution by 12 surgeons between August 2008 and December 2010. We performed
      univariable and multivariable analysis to measure the association between median
      lobe status and positive surgical margin rates, including site. RESULTS: Compared
      with patients without a median lobe (n=672), patients with a median lobe (n=119)
      were less likely to have a positive surgical margin (16% vs 24.4%). They had a
      higher prostate-specific antigen (PSA) level (6.1 ng/dL vs 5.4 ng/dL), lower
      Gleason scores (<7, 58.1% vs 42.1%), lower pathologic stages (T(2), 87.4% vs
      75.4%), and larger prostates (64 g vs 48 g) (all P<0.05). In our multivariable
      model, the effect of median lobe anatomy on surgical margin status, after
      adjusting for these factors, was not statistically significant (relative risk
      0.97, 95% confidence interval, 0.64-1.47, P=0.88). Lower PSA level, Gleason
      score, and pathologic stage and larger prostates, however, predicted decreased
      positive surgical margin rates (P<0.01). CONCLUSION: Although presence of median
      lobe anatomy is not an independent predictor of positive surgical margins in
      RALP, it is associated with favorable pathologic characteristics that are known
      to predict decreased positive surgical margins.

PMID- 21942800
TI  - Organ-specific radiation dose rates and effective dose rates during percutaneous
      nephrolithotomy.
AB  - BACKGROUND AND PURPOSE: Radiation exposure during medical procedures continues to
      be an increasing concern for physicians and patients. We determined organ
      specific dose rates and calculated effective dose rates during right and left
      percutaneous nephrolithotomy (PCNL) using a validated phantom model. MATERIALS
      AND METHODS: A validated anthropomorphic adult male phantom was placed prone on
      an operating room table. Metal oxide semiconductor field effect transistor
      dosimeters were placed at 20 organ locations in the model and were used to
      measure the organ dosages. A portable C-arm was used to provide continuous
      fluoroscopy for three 10 minute runs each to simulate a left and right PCNL.
      Organ dose rate (mGy/s) was determined by dividing organ dose by fluoroscopy
      time. The organ dose rates were multiplied by their tissue weighting factor and
      summed to determine effective dose rate (EDR) (mSv/s). Two-dimensional radiation
      distribution in the abdomen during a left-sided PCNL was visually determined
      using radiochromic film. RESULTS: The EDR for a left PCNL was 0.021 mSv/s +/-
      0.0008. The EDR for a right PCNL was 0.014 mSv/s +/- 0.0004. The skin entrance
      was exposed to the greatest amount of radiation during left and right PCNL, 0.24
      mGy/s and 0.26 mGy/s, respectively. Radiochromic film demonstrates visually the
      nonuniform dose distribution as the x-ray beam enters through the skin from the
      radiation source. CONCLUSIONS: The effective dose rate is higher for a left-sided
      PCNL compared with a right-sided PCNL. The distribution of radiation exposure
      during PCNL is not uniform. Further studies are needed to determine the long-term
      implications of these radiation doses during percutaneous stone removal.

PMID- 21942810
TI  - Serum HER-2/ECD analysis in monitoring breast cancer patients.

PMID- 21942811
TI  - Decreased mRNA expression of CCL5 [RANTES] in Alzheimer's disease blood samples.
AB  - BACKGROUND: A recent study reported that an 18-analyte multiplexed plasma panel
      of signaling proteins differentiated Alzheimer's disease (AD) from controls. This
      study measured mRNA expression for nine of these promising bio-markers in 23 AD
      patients and 23 age- and sex-matched controls. METHODS: Total RNA was isolated
      from PaxGene RNA tubes. Relative mRNA expression levels of CCL5 [RANTES], CSF1,
      ICAM1, IGFBP6, IL1A, IL3, IL8, PDGFB and TNF were determined by Q-RT-PCR, with
      GAPDH as housekeeping gene. RESULTS: A panel of five markers (CCL5, CSF1, ICAM1,
      IL8, TNF) with detectable expression levels in all individuals differed between
      AD patients and controls (p interaction <0.10). Especially, the relative
      expression level of CCL5 was lower in AD patients than in controls (p<0.005).
      Across groups, levels of both CCL5 and TNF were correlated to CSF levels of tau
      (r=0.39, r=0.32), ptau-181 (r=0.38, r=0.33), and MMSE (r=-0.31, r=-0.33, all
      p<0.05). CONCLUSIONS: The measured panel, and especially CCL5, could aid in the
      differentiation of AD from controls.

PMID- 21942812
TI  - Homosecoiridoids from the flower buds of Lonicera japonica.
AB  - Homosecoiridoids (1-15) were isolated from the flower buds of Lonicera japonica.
      Compounds 1-4, designated as loniphenyruviridosides A-D, possess unprecedented
      skeletons featuring phenylpyruvic acid derived moieties coupled with an iridoid
      or a secoiridoid nucleus. Compounds 5-15 (lonijaposides D-N) are additional
      examples of the unusual pyridinium alkaloid-coupled secoiridoids (lonijaposides A
      C). The validity of the CD data to determine the configuration of the secoiridoid
      derivatives is discussed on the basis of detailed CD data analysis and
      semisynthesis of 2 and 3 with the co-occurring secologanic acid. The
      configuration of secologanic acid was determined by a single-crystal X-ray
      crystallographic analysis using anomalous scattering of Cu Kalpha radiation.
      Biosynthetic pathways of the homosecoiridoids were postulated. Compounds 1-4
      inhibited STAT-3 activity of HELF cells, and lonijaposides F (7), H (9), I (10),
      and K (12) showed activity against the release of glucuronidase in rat
      polymorphonuclear leukocytes induced by platelet-activating factor.

PMID- 21942813
TI  - Can an iron-rich staple food help women to achieve dietary targets in pregnancy?
AB  - Habitual iron intakes during pregnancy are typically lower than dietary
      guidelines, a risk for iron deficiency. The aim of this study was to determine
      whether regular consumption of bread naturally rich in iron could help women to
      achieve dietary targets. Thirty-three primiparous mothers were randomized to eat
      3-4 slices of iron-rich or control bread daily for 6 weeks. Two 24-h-prompted
      (multiple-pass) dietary recalls were completed, and validated algorithms were
      used to determine the amount of 'available iron' from the diet. Regular
      consumption of iron-rich bread helped pregnant women to achieve UK dietary
      recommendations; the quantity of bread consumed by the participants contributed
      27% versus 9% UK Reference Nutrient Intake (RNI) (14.8 mg/d) in the intervention
      versus the control group. Levels of total 'available iron' were similar in both
      groups and correlated positively with total dietary iron (r = 0.78, P = 0.0001),
      vitamin C (r = 0.43, P = 0.017) and non-haem iron (r = 0.77, P = 0.0001).
      Findings from this study show that iron-rich staple foods can help women reach
      dietary targets for iron. This is an area of great potential that could be of
      particular benefit to low-income/ethnically diverse population groups who have
      some of the lowest iron intakes. Further research using fortified staple foods
      containing higher levels of iron is now warranted to establish physiological
      benefits.

PMID- 21942815
TI  - The prevalence of symptoms of Post-Traumatic Stress Disorder among soldiers with
      amputation of a limb or spinal injury: a report from a rehabilitation centre in
      Sri Lanka.
AB  - Post-Traumatic Stress Disorder has been identified as one of the most commonly
      occurring mental illnesses in combatants. This study was conducted to determine
      the prevalence of Post-Traumatic Stress Disorder among soldiers who had undergone
      amputation of a lower or an upper limb or sustained a spinal cord injury in the
      battlefield, and to compare the prevalence among these categories. The research
      presented seeks to increase the awareness of this condition among those treating
      war casualties so that appropriate treatment choices could be made to address
      them. The study was carried out in 2009 at a rehabilitation centre for combatants
      of war. Data were collected from 96 male army veterans between the ages of 18-49
      years using a pre-tested self-administered questionnaire based on the Diagnostic
      and Statistical Manual of Mental Disorders, the Impact of Event Scale and the
      PTSD symptom scale. Soldiers with injuries sustained at least four weeks prior to
      the study were selected by a convenience sampling technique. Soldiers with
      multiple injuries, head injuries or those diagnosed with psychiatric disorders
      were excluded. The results revealed that 41.7% of the study population was
      compatible with the diagnosis of Post-Traumatic Stress Disorder. Within the three
      groups, 42.5% of the lower limb amputees, 33.3% of the upper limb amputees and
      45.7% of the participants with spinal cord injury had symptoms compatible with
      Post-Traumatic Stress Disorder. There was no difference between the prevalence
      among the different injury categories considered. This study highlights the need
      to pay more attention in providing psychological care as a part of the overall
      health management of injured combatants. Early preparation of soldiers for
      stressors of war and screening for and proper management of Post-Traumatic Stress
      Disorder will improve the overall outcome of rehabilitation.

PMID- 21942816
TI  - Sensitive quantification of somatic mutations using molecular inversion probes.
AB  - Somatic mutations in DNA can serve as cancer specific biomarkers and are
      increasingly being used to direct treatment. However, they can be difficult to
      detect in tissue biopsies because there is often only a minimal amount of sample
      and the mutations are often masked by the presence of wild type alleles from
      nontumor material in the sample. To facilitate the sensitive and specific
      analysis of DNA mutations in tissues, a multiplex assay capable of detecting
      nucleotide changes in less than 150 cells was developed. The assay extends the
      application of molecular inversion probes to enable sensitive discrimination and
      quantification of nucleotide mutations that are present in less than 0.1% of a
      cell population. The assay was characterized by detecting selected mutations in
      the KRAS gene, which has been implicated in up to 25% of all cancers. These
      mutations were detected in a single multiplex assay by incorporating the rapid
      flow cytometric readout of multiplexable DNA biosensors.

PMID- 21942817
TI  - QTAIM investigation of the electronic structure and large Raman scattering
      intensity of bicyclo-[1.1.1]-pentane.
AB  - Our previous studies of the variation of Raman scattering intensities in
      saturated hydrocarbons have identified a number of structural descriptors that
      correlate with calculated polarizability derivatives for particular bond
      displacements: ring strain, steric hindrance, and alignment and location of a C-H
      group within the molecular framework (e.g., endo-/exo-, axial/equatorial, in
      plane/out-of-plane). The bridgehead C-H bond intensities in bicyclo-[1.1.1]
      pentane appear to be extraordinarily large, given its size and structure.
      Molecular polarizability and derivatives are analyzed here for bicyclo-[1.1.1]
      pentane and propane, with HF, MP2, CCSD, B3LYP, M06, and M062X levels of theory
      and the Dunning AVTZ basis set. Analyses of calculated electronic charge
      densities were performed with two implementations of QTAIM, including an origin
      dependent method and an implementation with origin-independent atomic moments.
      Numerically accurate atomic partitioning of mean molecular polarizabilities is
      achievable with either; however, accurate partitioning of polarizability
      derivatives places stringent requirements on the numerical integration, more so
      for this highly strained bicyclic structure. QTAIM reveals that most of the
      polarizability (~90%) can be attributed to charge transfer between atomic basins.
      Calculated Raman intensities are in accord with our experimental data, notably in
      the prediction of large trace scattering intensities for stretching of the
      bridgehead CH in bicyclo-[1.1.1]-pentane and for the methyl in-plane C-H in
      propane. Density difference plots illustrate the effects of bond displacements on
      the electron densities and the resultant changes in polarizability. Stretching of
      the bridgehead C-H bond in bicyclo-[1.1.1]-pentane produces electron density
      changes that are similar to those encountered upon stretching the methyl in-plane
      C-H of propane.

PMID- 21942818
TI  - Fluorescent imidazolium-based cyclophane for detection of guanosine-5'
      triphosphate and I(-) in aqueous solution of physiological pH.
AB  - A new water-soluble and fluorescent imidazolium-anthracene cyclophane (1)
      effectively recognizes the biologically important GTP and I(-) over other anions
      in a 100% aqueous solution of physiological pH 7.4. Fluorescence and (1)H NMR
      spectra and ab initio calculations demonstrate that emission arises from the
      formation of an excimer state and quenching occurs upon GTP/I(-) binding through
      (C-H)(+)...A(-) hydrogen bond interactions.

PMID- 21942814
TI  - Pregnancy outcomes in women with advanced HIV infection in Italy.
AB  - Pregnancy has been associated with a low risk of HIV disease progression. Most
      pregnancies with HIV currently involve women who have not experienced AIDS
      defining events, and are clinically classified as Centers for Disease Control and
      Prevention (CDC) groups A or B. We evaluated the main maternal outcomes among
      pregnant women with more advanced HIV disease, defined by CDC-C disease stage.
      Data from the Italian National Program on Surveillance on Antiretroviral
      Treatment in Pregnancy were used. A total of 566 HIV-infected mothers, 515 in
      stage A or B (CDC-AB group) and 51 in stage C (CDC-C group) were evaluated. The
      two groups had similar baseline characteristics. No differences were found in the
      main maternal and neonatal outcomes. Most of the women achieved viral suppression
      at end of pregnancy (>1000 copies per milliliter: CDC-C: 17.2%; CDC-AB: 13.7%).
      One year after delivery, HIV replication (HIV-RNA >1000 copies per milliliter)
      was present in 11.5% of CDC-AB women and 30.0% CDC-C women. Despite lower initial
      CD4 counts (300 versus 481 cells per microliter), CDC-C women maintained stable
      CD4 levels during pregnancy, and 1 year after delivery, a significant increase in
      CD4 count from preconception values was observed in both groups (CDC-C: +72 cells
      per microliter, p=0.031; CDC-AB: +43 cells per microliter, p<0.001). Only one
      AIDS event occurred in a woman with a previous diagnosis of AIDS. In CDC-C women,
      pregnancy is not associated with an increased rate of adverse maternal or
      neonatal outcomes, and a good immunovirologic response can be expected. During
      postpartum care, women with more advanced HIV infection should receive particular
      care to prevent loss of virologic suppression.

PMID- 21942819
TI  - Emotional labor in American professors.
AB  - An online survey was conducted on a national sample of United States professors
      to examine emotional labor and its relationship to work outcomes. Participants
      were queried on genuine, faking, and suppressing emotional expression facets of
      emotional labor, as well as emotional exhaustion, job satisfaction, and affective
      commitment. The sample of 598 included 71 instructors, 177 assistant professors,
      168 associate professors, and 182 professors. A path analysis was conducted
      testing two models of emotional labor. Results supported a model indicating
      significant direct relationships between emotional labor, emotional exhaustion,
      and job satisfaction. Additionally, the relationship between emotional labor and
      affective commitment was mediated by emotional exhaustion and job satisfaction.
      Genuine positive expression was the only emotional labor variable to have
      significant direct relationships with all outcomes. For U.S. faculty, the
      experience of emotional labor was related to several work attitudes.

PMID- 21942820
TI  - Job stress and family social behavior: the moderating role of neuroticism.
AB  - We investigated the role of neuroticism in the associations between job stress
      and working adults' social behavior during the first hour after work with their
      spouse and school-age children. Thirty dual-earner families were videotaped in
      their homes on two weekday afternoons and evenings. An observational coding
      system was developed to assess behavioral involvement and negative emotion
      expression. Participants also completed self-report measures of job stressors and
      trait neuroticism. There were few overall associations between job stress and
      social behavior during the first hour adults were at home with their spouse and
      school-age children. However, significant moderator effects indicated that
      linkages between work experiences and family behavior varied for men who reported
      different levels of trait neuroticism, which captures a dispositional tendency
      toward emotional instability. Among men who reported high neuroticism, job stress
      was linked to more active and more negative social behavior. Conversely, for men
      reporting low neuroticism, job stress was related to less talking and less
      negative emotion. These patterns were not found for the women in the study. The
      findings suggest that when work is stressful, men who are higher on neuroticism
      (i.e., less emotionally stable) may show a negative spillover effect, whereas men
      who are lower on neuroticism (i.e., more emotionally stable) may withdraw from
      social interactions.

PMID- 21942822
TI  - Toxicity of individual naphthenic acids to Vibrio fischeri.
AB  - Numerous studies have suggested that the toxicity of organic compounds containing
      at least one carboxylic acid group and broadly classified as "naphthenic acids",
      is of environmental concern. For example, the acute toxicity of the more than 1
      billion m(3) of oil sands process-affected water and the hormonal activity of
      some offshore produced waters has been attributed to the acids. However,
      experimental evidence for the toxicity of the individual acids causing these
      effects has not been very forthcoming. Instead, most data have been gathered from
      assays of incompletely characterized extracts of the water, which may contain
      other toxic constituents. An alternative approach is to assay the individual
      identified toxicants. Since numerous petroleum-derived naphthenic acids and some
      in oil sands process water, have recently been identified, we were able to
      measure the toxicity of some individual acids to the bioluminescent bacterium,
      Vibrio fischeri. Thirty-five pure individual acids were either synthesized or
      purchased for this purpose. We also used the US EPA ECOSAR computer model to
      predict the toxicity of each acid to the water flea, Daphnia magna. Both are well
      accepted toxicological screening end points. The results show how toxic some of
      the naphthenic acids really are (e.g., V. fischeri Effective Concentrations for
      50% response (EC(50)) 0.004 to 0.7 mM) and reveal the influence of hydrophobicity
      and aqueous solubility on the toxicities. Comparison with measured toxicities of
      other known, but more minor, constituents of oil sands process water, such as
      polycyclic aromatic hydrocarbons and alkylphenols, helps place these toxicities
      into a wider context. Given the reported toxicological effects of naphthenic
      acids to other organisms (e.g., fish, plants), the toxicities of the acids to
      further end points should now be determined.

PMID- 21942823
TI  - Revisiting peptide amphiphilicity for membrane pore formation.
AB  - It has previously been shown that an amphipathic de novo designed peptide made of
      10 leucines and four phenylalanines substituted with crown ethers induces vesicle
      leakage without selectivity. To gain selectivity against negatively charged
      dimyristoylphosphatidylglycerol (DMPG) bilayers, one or two leucines of the
      peptide were substituted with positively charged residues at each position. All
      peptides induce significant calcein leakage of DMPG vesicles. However, some
      peptides do not induce significant leakage of zwitterionic
      dimyristoylphosphatidylcholine vesicles and are thus active against only
      bacterial model membranes. The intravesicular leakage is induced by pore
      formation instead of membrane micellization. Nonselective peptides are mostly
      helical, while selective peptides mainly adopt an intermolecular beta-sheet
      structure. This study therefore demonstrates that the position of the lysine
      residues significantly influences the secondary structure and bilayer selectivity
      of an amphipathic 14-mer peptide, with beta-sheet peptides being more selective
      than helical peptides.

PMID- 21942824
TI  - On the viscosity of pyridinium based ionic liquids: an experimental and
      computational study.
AB  - A study on the viscosity of eight pyridinium based ionic liquids is reported for
      wide pressure and temperature ranges. Measurements were performed using an
      electromagnetic moving piston viscometer. Experimental data were fitted to a Tait
      like equation demonstrating good correlations, which was used to calculate
      pressure/viscosity and temperature/viscosity coefficients. The effect of the
      involved anions and cation on the ionic liquid viscosity was analyzed from a
      molecular viewpoint using hole theory, quantum chemistry calculations using
      density functional theory, and classical molecular dynamics simulations. The
      analysis of the experimental and computational results shows the complex effects
      controlling viscosity of studied fluids, including strength of ionic pairs,
      molecular sizes, and mobility and effects rising from the availability and cavity
      sizes distributions in pyridinium-based ionic liquids.

PMID- 21942825
TI  - A "snapshot" of declarative memory: Differing developmental trajectories in
      episodic and autobiographical memory.
AB  - Episodic and autobiographical memory are clearly related, yet in both the adult
      and developmental literatures it is difficult to compare them because of
      differences in how the constructs are assessed, including differences in content,
      levels of control, and time since experience. To address these issues, we
      directly compared children's and adults' autobiographical and episodic memory
      using the same controlled paradigm. Participants engaged in a photo-taking
      activity in a museum (autobiographical encoding) and viewed others' photographs
      of the same museum exhibits (episodic encoding). At test, participants classified
      photos as ones they took, viewed, or novel. In the autobiographical condition
      older children and adults performed similarly; younger children's performance was
      lower than adults'. In contrast, in the episodic condition both groups of
      children performed more poorly than adults. The findings suggest the
      developmental primacy of autobiographical relative to episodic memory, and that
      traditional episodic tasks may underestimate older children's declarative memory
      abilities.

PMID- 21942841
TI  - Feasibility and safety of adoptive immunotherapy with ex vivo-generated
      autologous, cytotoxic T lymphocytes in patients with solid tumor.
AB  - BACKGROUND AIMS: Adoptive T-cell therapy with tumor-specific T cells has emerged
      as a potentially useful approach for treating patients with advanced
      malignancies. We have demonstrated previously the feasibility of obtaining large
      numbers of autologous anti-tumor-specific cytotoxic T lymphocytes (CTL) generated
      by stimulation of patients' peripheral blood mononuclear cells with dendritic
      cells pulsed with apoptotic tumor cells. Methods. Six patients with progressing
      metastatic solid tumors (one renal cell carcinoma, two ovarian cancers, two
      extraosseous peripheral neuroectodermal tumors, one soft tissue sarcoma) not
      eligible for conventional therapies were treated with adoptive immunotherapy.
      Anti-tumor CTL, proven to be reactive in vitro against patient tumor cells, but
      not against normal cells, were infused following lymphodepleting chemotherapy
      administered to favor T-cell proliferation in vivo. RESULTS: Patients received a
      median of nine CTL infusions (range 2-19). The median number of CTL administered
      per infusion was 11 * 10(8) (range 1-55 * 10(8)). No patient experienced acute or
      late adverse events related to CTL infusion, even when large numbers of cells
      were given. Post-infusion laboratory investigations demonstrated an increase in
      the frequency of circulating anti-tumor T-cells and, in patients with a longer
      follow-up receiving two CTL infusions/year, a stabilization of these values.
      CONCLUSIONS: Our study demonstrates that autologous ex vivo-generated anti-tumor
      CTL can be administered safely in patients with advanced solid tumors and can
      improve the immunologic reactivity of recipients against tumor. These preliminary
      results provide a rationale for evaluating the clinical efficacy of this
      immunotherapeutic approach in phase I/II studies.

PMID- 21942842
TI  - Allogeneic bone marrow stromal cell transplantation after cerebral hemorrhage
      achieves cell transdifferentiation and modulates endogenous neurogenesis.
AB  - BACKGROUND AIMS: When a severe neurologic lesion occurs as a consequence of
      intracerebral hemorrhage (ICH), there is no effective treatment available for
      improving the outcome. However, cell therapy has opened new perspectives on
      reducing neurologic sequels subsequent to this disease. METHODS: In this study,
      ICH was induced by stereotactic injection of 0.5 U collagenase type IV in the
      striatum of adult Wistar rats, and 2 h later a group of animals (n = 48) was
      subjected to intracerebral injection of 2 * 10(6) allogeneic bone marrow stromal
      cells (BMSC), while a control group (n = 48) received saline only. Eight animals
      from each group were killed at 48 h, 72 h, 7 days, 14 days, 21 days and 28 days.
      At these time-points, endogenous neurogenesis and survival of transplanted BMSC
      were studied. RESULTS: Our findings show that after allogeneic BMSC
      transplantation, donor cells can survive in the brain tissue expressing neuronal
      and astroglial markers. Furthermore, BMSC transplantation enhances endogenous
      neurogenesis and inhibits apoptosis of newborn neural cells. CONCLUSIONS:
      Although these results should be extrapolated to human disease with caution, it
      is obvious that cell therapy using allogeneic BMSC transplantation offers great
      promise for developing novel and efficacious strategies in patients suffering
      ICH.

PMID- 21942843
TI  - Essential oils in insect control: low-risk products in a high-stakes world.
AB  - In recent years, the use of essential oils (EOs) derived from aromatic plants as
      low-risk insecticides has increased considerably owing to their popularity with
      organic growers and environmentally conscious consumers. EOs are easily produced
      by steam distillation of plant material and contain many volatile, low-molecular
      weight terpenes and phenolics. The major plant families from which EOs are
      extracted include Myrtaceae, Lauraceae, Lamiaceae, and Asteraceae. EOs have
      repellent, insecticidal, and growth-reducing effects on a variety of insects.
      They have been used effectively to control preharvest and postharvest
      phytophagous insects and as insect repellents for biting flies and for home and
      garden insects. The compounds exert their activities on insects through
      neurotoxic effects involving several mechanisms, notably through GABA, octopamine
      synapses, and the inhibition of acetylcholinesterase. With a few exceptions,
      their mammalian toxicity is low and environmental persistence is short.
      Registration has been the main bottleneck in putting new products on the market,
      but more EOs have been approved for use in the United States than elsewhere owing
      to reduced-risk processes for these materials.

PMID- 21942844
TI  - Managing social insects of urban importance.
AB  - Social insects have a tremendous economic and social impact on urban communities.
      The rapid urbanization of the world has dramatically increased the incidence of
      urban pests. Human commerce has resulted in the spread of urban invasive species
      worldwide such that various species are now common to many major urban centers.
      We aim to highlight those social behaviors that can be exploited to control these
      pests with the minimal use of pesticides. Their cryptic behavior often prohibits
      the direct treatment of colonies. However, foraging and recruitment are essential
      aspects of their social behavior and expose workers to traps, baits, and
      pesticide applications. The advent of new chemistries has revolutionized the pest
      management strategies used to control them. In recent years, there has been an
      increased environmental awareness, especially in the urban community. Advances in
      molecular and microbial agents promise additional tools in developing integrated
      pest management programs against social insects.

PMID- 21942845
TI  - Mosquito genomics: progress and challenges.
AB  - The whole-genome sequencing of mosquitoes has facilitated our understanding of
      fundamental biological processes at their basic molecular levels and holds
      potential for application to mosquito control and prevention of mosquito-borne
      disease transmission. Draft genome sequences are available for Anopheles gambiae,
      Aedes aegypti, and Culex quinquefasciatus. Collectively, these represent the
      major vectors of African malaria, dengue fever and yellow fever viruses, and
      lymphatic filariasis, respectively. Rapid advances in genome technologies have
      revealed detailed information on genome architecture as well as phenotype
      specific transcriptomics and proteomics. These resources allow for detailed
      comparative analyses within and across populations as well as species. Next
      generation sequencing technologies will likely promote a proliferation of genome
      sequences for additional mosquito species as well as for individual insects. Here
      we review the current status of genome research in mosquitoes and identify
      potential areas for further investigations.

PMID- 21942847
TI  - Production of unusual dispiro metabolites in Pestalotiopsis virgatula endophyte
      cultures: HPLC-SPE-NMR, electronic circular dichroism, and time-dependent density
      functional computation study.
AB  - The endophytic fungus Pestalotiopsis virgatula, derived from the plant Terminalia
      chebula and previously found to produce a large excess of a single metabolite
      when grown in the minimal M1D medium, was induced to produce a variety of unusual
      metabolites by growing in potato dextrose broth medium. Analysis of the
      fermentation medium extract was performed using an HPLC-PDA-MS-SPE-NMR hyphenated
      system, which led to the identification of a total of eight metabolites (1-8),
      six of which are new. Most of the metabolites are structurally related and are
      derivatives of benzo[c]oxepin, rare among natural products. This includes dispiro
      derivatives 7 and 8 (pestalospiranes A and B), having a novel 1,9,11,18
      tetraoxadispiro[6.2.6.2]octadecane skeleton. Relative and absolute configurations
      of the latter were determined by a combination of NOESY spectroscopy and
      electronic circular dichroism spectroscopy supported by time-dependent density
      functional theory calculations (B3LYP/TZVP level). This work demonstrates that a
      largely complete structure elucidation of numerous metabolites present in a raw
      fermentation medium extract can be performed by the HPLC-SPE-NMR technique using
      only a small amount of the extract, even with unstable metabolites that are
      difficult to isolate by traditional methods.

PMID- 21942846
TI  - Micropatterned aptasensors for continuous monitoring of cytokine release from
      human leukocytes.
AB  - We report the development of a microdevice for detecting local interferon gamma
      (IFN-gamma) release from primary human leukocytes in real time. Our microdevice
      makes use of miniature aptamer-modified electrodes integrated with microfluidics
      to monitor cellular production of IFN-gamma. The aptamer species consists of a
      DNA hairpin molecule with thiol groups on the 3'-end for self-assembly onto Au
      electrodes. A redox reporter is covalently attached at the 5'-end for
      electrochemical sensing. This aptasensor has excellent sensitivity for IFN-gamma
      (<60 pM detection limit) and responds to the target analyte in real time without
      additional washing or labeling steps. Aptamer-functionalized electrode arrays are
      fabricated on glass slides containing poly(ethylene glycol) (PEG) hydrogel
      patterns designed to expose glass regions adjacent to electrodes while protecting
      the remainder of the surface from nonspecific adsorption. The micropatterned
      substrates are integrated with PDMS microfluidic channels and incubated with T
      cell-specific antibodies (Ab) (anti-CD4). Upon injection of blood, leukocytes are
      bound to Ab-modified glass regions in proximity to aptasensors. Cytokine release
      from captured cells is triggered by mitogenic activation and detected at the
      aptamer-modified electrodes using square wave voltammetry (SWV). The IFN-gamma
      signal is monitored in real time with signal appearing as early as 15 min
      poststimulation from as few as 90 T cells. The observed IFN-gamma release
      profiles are used to calculate an initial IFN-gamma production rate of 0.0079 pg
      cell(-1) h(-1) upon activation. The work described here represents an important
      step toward development of aptasensors for immune cell analysis and blood-based
      diagnostics.

PMID- 21942848
TI  - Thromboelastometric (ROTEM) findings in patients suffering from isolated severe
      traumatic brain injury.
AB  - Severe traumatic brain injury (sTBI) is often accompanied by coagulopathy and an
      increased risk of bleeding. To identify and successfully treat bleeding disorders
      associated with sTBI, rapid assessment of coagulation status is crucial. This
      retrospective study was designed to assess the potential role of whole-blood
      thromboelastometry (ROTEM((r)), Tem International, Munich, Germany) in patients
      with isolated sTBI (abbreviated injury scale [AIS](head) >=3 and
      AIS(extracranial) <3). Blood samples were obtained immediately following
      admission to the emergency room of the Trauma Centre Salzburg in Austria. ROTEM
      analysis (EXTEM, INTEM, and FIBTEM tests) and standard laboratory coagulation
      tests (prothrombin time index [PTI, percentage of normal prothrombin time],
      activated partial thromboplastin time [aPTT], fibrinogen concentration, and
      platelet count) were compared between survivors and non-survivors. Out of 88
      patients with sTBI enrolled in the study, 66 survived and 22 died. PTI,
      fibrinogen, and platelet count were significantly higher in survivors (p<0.005).
      Accordingly, aPTT was shorter in this group (p<0.0001). ROTEM analysis revealed
      shorter clotting times in extrinsically activated thromboelastometric test
      (EXTEM) and intrinsically activated thromboelastometric test (INTEM) (p<0.001),
      shorter clot formation times in EXTEM and INTEM (p<0.0001), and higher maximum
      clot firmness in EXTEM, INTEM, and FIBTEM (p<0.01) in survivors compared with non
      survivors. Logistic regression analysis revealed extrinsically activated
      thromboelastometric test with cytochalasin D (FIBTEM) MCF and aPTT to have the
      best predictive value for mortality. According to the degree of coagulopathy, non
      survivors received more RBC (p=0.016), fibrinogen concentrate (p=0.01), and
      prothrombin complex concentrate (p<0.001) within 24 h of arrival in the emergency
      room. ROTEM testing appeared to offer an early signal of severe life-threatening
      sTBI. Further studies are warranted to confirm these results and to investigate
      the role of ROTEM in guiding coagulation therapy.

PMID- 21942849
TI  - C-statistics versus logistic regression for assessing the performance of
      qualitative diagnostic tests.
AB  - BACKGROUND: Qualitative diagnostic tests commonly produce false positive and
      false negative results. Smooth receiver operated characteristic (ROC) curves are
      used for assessing the performance of a new test against a standard test. This
      method, called c-statistic (concordance) has limitations. The aim of this study
      was to assess whether logistic regression with the odds of disease as an outcome
      and the test scores as covariate, can be used as an alternative approach, and to
      compare the performance of either of the two methods. METHODS: Using as examples
      simulated by vascular laboratory scores we assessed the performance of logistic
      regression as compared to c-statistics. RESULTS: The c-statistics produced areas
      under the curve (AUCs) of respectively 0.954 and 0.969 (standard errors 0.007 and
      0.005), means difference 0.015 with a pooled standard error of 0.0086. This meant
      that the new test was not significantly different from the standard test at
      p=0.08. Logistic regression of these data with presence of disease as a dependent
      and vascular laboratory scores as an independent variable produced regression
      coefficients of 0.45 and 0.58 with standard errors of respectively 0.04 and 0.05.
      This meant that the new test was a significantly better predictor of disease than
      the standard test at p=0.04. CONCLUSIONS: Logistic regression with presence of
      disease as a dependent and test scores as an independent variable was better than
      c-statistics for assessing qualitative diagnostic tests. This may be relevant to
      future diagnostic research.

PMID- 21942850
TI  - Comparison of vancomycin concentrations in blood and interstitial fluid: a
      possible model for less invasive therapeutic drug monitoring.

PMID- 21942851
TI  - External quality assessment of point-of-care International Normalized Ratio (INR)
      testing in Europe.
AB  - BACKGROUND: Point-of-care testing (POCT) of prothrombin time, expressed as
      International Normalized Ratio (INR), is widely used to monitor patients in oral
      anticoagulation treatment. Guidelines recommend that POCT users should
      participate in an external quality assessment (EQA) scheme whenever available.
      The aim of this study was to investigate which European countries provide EQA for
      POCT INR and to compare how these schemes are organized. METHODS: Thirty European
      countries were invited to participate in this study. Those who reported that they
      provide EQA for POCT INR filled in a questionnaire dealing with different aspects
      of their schemes. RESULTS: Nineteen countries reported that they do not provide
      EQA for POCT INR, while 12 organizations from nine countries reported that they
      provide this service. Most of these countries circulate lyophilized samples with
      for the participants unknown target values. Samples with certified INR values and
      procedures using split samples with fresh patient samples are also used. The
      acceptability limits vary from 15% to 30%, and the total number of samples
      circulated per year varies from 1 to 12. Most of the countries organize
      educational activities together with their schemes. CONCLUSIONS: This study
      demonstrates that there is a wide variation in the way EQA for POCT INR is
      performed in Europe and that there are many European countries that do not
      provide this service. Even though our findings indicate that EQA for POCT INR
      draws some challenges, especially in providing suitable control materials,
      participation in such schemes is considered useful.

PMID- 21942852
TI  - Evaluation of Aution Max AX-4030 and 9UB Uriflet, 10PA Aution Sticks urine
      dipsticks in the automated urine test strip analysis.
AB  - BACKGROUND: Aution Max AX-4030, a test strip analyzer recently introduced to the
      market, represents an upgrade of the Aution Max AX-4280 widely employed for
      urinalysis. This new instrument model can allocate two different test strips at
      the same time. In the present study the two instruments have been compared
      together with the usage of Uriflet 9UB and the recently produced Aution Sticks
      10PA urine strips, the latter presenting an additional test area for the
      measurement of urinary creatinine. METHODS: Imprecision and correlation between
      instruments and strips have been evaluated for chemical-physical parameters.
      Accuracy was evaluated for protein, glucose and creatinine by comparing the semi
      quantitative results to those obtained by quantitative methods. The well-known
      interference effect of high ascorbic acid levels on urine glucose test strip
      determination was evaluated, ascorbic acid influence was also evaluated on
      protein and creatinine determination. RESULTS: The two instruments have
      demonstrated comparable performances: precision and correlation between
      instruments and strips, evaluated for chemical-physical parameters, were always
      good. Furthermore, accuracy was always very good: results of protein and glucose
      semi-quantitative measurements resulted to be highly correlated with those
      obtained by quantitative methods. Moreover, the semi-quantitative measurements of
      creatinine, employing Aution Sticks 10PA urine strips, were highly comparable
      with quantitative results. CONCLUSIONS: 10PA urine strips are eligible for urine
      creatinine determination with the possibility of correcting urinalysis results
      for urinary creatinine concentration, whenever necessary and calculating the
      protein creatinine ratio. Further studies should be carried out to evaluate
      effectiveness and appropriateness of the usage of creatinine semi-quantitative
      analysis.

PMID- 21942853
TI  - Analytical performances of cystatin C turbidimetric assay: which impact on
      accuracy of glomerular filtration rate estimation in renal transplantation?
AB  - BACKGROUND: The potential use of cystatin C has recently emerged to evaluate
      kidney function following transplantation. Analytical performance of a particle
      enhanced turbidimetric immunoassay (PETIA) using Dako Cytomation Cystatin C
      reagents on an Olympus AU640((r)) analyzer was evaluated. Clinical relevance was
      determined by comparison with a reference method in a kidney transplant cohort.
      METHODS: Repeatability and reproducibility were carried out for four levels of
      cystatin C. Linearity was done by successive dilution of plasma samples with high
      level of cystatin C. Comparison study was performed against the particle-enhanced
      nephelemetry immunoassay (PENIA) using Siemens reagents on BNII((r)) system.
      Values of the glomerular filtration rate (GFR) estimated from several predictive
      cystatin C- and creatinine-based equations were compared to the GFR measured by
      isotopic method ((99m)Tc-DTPA). These predictive algorithms were analyzed with
      respect to bias, precision and accuracy. RESULTS: Total intra-assay and inter
      assay variation coefficients were below 4% at the four levels tested. Values
      obtained with Dako-PETIA on AU640((r)) were correlated with the Siemens-PENIA
      method (Dako-Olympus=0.88 Siemens+0.17). The cystatin C alone and the creatinine
      cystatin C combined equation allowed reliable assessment of GFR in our population
      of renal transplants. The cystatin C-based or the combined equation moderately
      improved determination of GFR (about 10% compared to 175MDRD for classification
      into the correct K/DOQI CKD stages). CONCLUSIONS: The use of algorithms based on
      cystatin C and creatinine could provide a reliable estimate of the GFR in kidney
      transplantation. Standardization of cystatin C assays could further improve the
      predicting value of cystatin C in transplantation.

PMID- 21942854
TI  - The old and new tests for celiac disease: which is the best test combination to
      diagnose celiac disease in pediatric patients?
AB  - BACKGROUND: In the diagnosis of celiac disease (CD), serum assays for anti
      endomysium (EMA) and anti-transglutaminase (anti-tTG) antibodies have excellent
      diagnostic accuracy. However, these assays are less sensitive in young pediatric
      patients. Recently, a new ELISA test using deamidated gliadin peptides (DGP) as
      antigen has proved to be very sensitive and specific even in pediatric patients.
      In addition, anti-actin IgA antibodies (AAA) is another test that can be used in
      CD patients because antibody concentrations correlate with the degree of villous
      atrophy. This study evaluated the clinical accuracy of anti-tTG, EMA, AGA, anti
      DGP and AAA and the effectiveness of these in different combinations for
      diagnosing CD in a large cohort of pediatric patients. METHODS: Sera of 150
      children under 6 years of age were tested: 95 patients had a diagnosis of CD,
      while 55 patients who did not suffer from CD were used as controls. Anti-DGP
      IgA/IgG and AAA were assayed with ELISA kits, while anti-tTG IgA/IgG and AGA
      IgG/IgA were assayed using a quantitative fluoroimmunoassay. The EMA test was
      conducted by indirect immunofluorescence. RESULTS: Seventy-six of 95 (80%) CD
      patients were positive for DGP IgA and/or tTG IgA. Eighty of 95 (84.2%) patients
      were positive for DGP IgG and/or tTG IgA. None of the controls were positive for
      these antibodies. Eighty-four of 95 (88.4%) patients and 8/55 (14.5%) controls
      were positive for AAA and/or anti-tTG IgA. CONCLUSIONS: In very young children,
      association of anti-tTG IgA with anti-DGP IgG is the best test combination for
      diagnosing CD, yielding a cumulative sensitivity of 84.2% and a specificity of
      100%.

PMID- 21942855
TI  - Design considerations on the proof of efficacy of functional foods.
AB  - Functional food research encompasses several types of study designs, including
      observational studies and randomized clinical trials (RCTs). Markers that can
      predict potential benefits or risks relating to certain health conditions are
      often the primary endpoints of such studies since a direct measurement of the
      effect of food on health and well-being and/or reduction of disease risk is often
      not possible. Whether RCT should be at the top of the pyramid also in nutritional
      research remains a controversial issue. Undoubtedly, further research is needed
      to redesign RCT methodology that would adequately serve the need to demonstrate
      the health effects of foods. We address this functional food research question by
      assuming that there is a known relationship between the surrogate and the true
      endpoint explored during the surrogacy assessment. Statistical inference on the
      true (unobserved) endpoint is derived on the basis of its predicted values. We
      illustrate this approach through a motivating example from the literature on
      coronary heart disease, integrated with simulated scenarios.

PMID- 21942856
TI  - Identification and quantitation of 3-S-cysteinylglycinehexan-1-ol (Cysgly-3-MH)
      in Sauvignon blanc grape juice by HPLC-MS/MS.
AB  - Precursors to varietal wine thiols are a key area of grape and wine research.
      Several such precursors, in the form of odorless conjugates, have been closely
      studied in recent years. A new conjugate has now been identified as 3-S
      cysteinylglycinehexan-1-ol (Cysgly-3-MH), being the dipeptide intermediate
      between cysteine and glutathione precursors of tropical thiol 3-mercaptohexan-1
      ol (3-MH). Authentic Cysgly-3-MH was produced via enzymatic transformation of the
      glutathione conjugate and used to verify the presence of both diastereomers of
      Cysgly-3-MH in Sauvignon blanc juice extracts. Cysgly-3-MH was added into our
      HPLC-MS/MS precursor method, and the validated method was used to quantify this
      new analyte in a selection of Sauvignon blanc juice extracts. Cysgly-3-MH was
      found in the highest concentrations (10-28.5 MUg/L combined diastereomer total)
      in extracts from berries that had been machine-harvested and transported for 800
      km in 12 h. This dipeptide conjugate was much less abundant than the glutathione
      and cysteine conjugates in the samples studied. On the basis of the results, the
      new cysteinylglycine conjugate of 3-MH seemingly has a short existence as an
      intermediate precursor, which may explain why it has not been identified as a
      natural juice component until now.

PMID- 21942857
TI  - Google Calendar: a new memory aid to compensate for prospective memory deficits
      following acquired brain injury.
AB  - Prospective memory impairment is common following acquired brain injury (ABI) and
      intervention has proved challenging. The current treatment of choice involves
      using external memory aids as a method of compensation, with those incorporating
      active reminders proving most successful. In this paper we report findings of an
      investigation into the effectiveness of a novel external memory aid, Google
      Calendar. This aid incorporates active reminders and overcomes some of the
      limitations associated with existing aids. Twelve participants with ABI took part
      in the study incorporating a randomised control crossover within-subjects design,
      consisting of a 5-week baseline phase, followed by two 5-week intervention phases
      where either Google Calendar or a standard diary were used. Participants
      identified activities to target during the study and a family member monitored
      their success. Google Calendar was more effective than the diary in enhancing
      prospective memory performance. It also proved more popular, on account of its
      active reminders which helped trigger the retrieval of intentions, whilst
      reducing the need for monitoring. While further research is required to
      substantiate these initial findings, it is recommended that clinicians
      familiarise themselves with using Google Calendar, as it appears to offer
      additional potential in the management of prospective memory deficits following
      ABI.

PMID- 21942864
TI  - Membrane disruption and early events in the aggregation of the diabetes related
      peptide IAPP from a molecular perspective.
AB  - The aggregation of proteins is tightly controlled in living systems, and
      misfolded proteins are normally removed before aggregation of the misfolded
      protein can occur. But for reasons not clearly understood, in some individuals
      this degradation process breaks down, and misfolded proteins accumulate in
      insoluble protein aggregates (amyloid deposits) over time. Of the many proteins
      expressed in humans, a small but growing number have been found to form the long,
      highly ordered beta-sheet protein fibers that comprise amyloid deposits. Despite
      a lack of obvious sequence similarity, the amyloid forms of diverse proteins are
      strikingly similar, consisting of long, highly ordered insoluble fibers with a
      characteristic crossed beta-sheet pattern. Amyloidogenesis has been the focus of
      intense basic and clinical research, because a high proportion of amyloidogenic
      proteins have been linked to common degenerative diseases, including Alzheimer's
      disease, type II diabetes, and Parkinson's disease.  The apparent link between
      amyloidogenic proteins and disease was initially attributed to the amyloid form
      of the protein; however, increasing evidence suggests that the toxicity is due to
      intermediates generated during the assembly of amyloid fibers. These
      intermediates have been proposed to attack cells in a variety of ways, such as by
      generating inflammation, creating reactive oxygen species, and overloading the
      misfolded protein response pathway. One common, well-studied mechanism is the
      disruption of the plasma and organelle membranes.  In this Account, we examine
      the early molecular-level events in the aggregation of the islet amyloid
      polypeptide (IAPP, also called amylin) and its ensuing disruption of membranes.
      IAPP is a 37-residue peptide secreted in conjunction with insulin; it is highly
      amyloidogenic and often found in amyloid deposits in type II diabetics. IAPP
      aggregates are highly toxic to the beta-cells that produce insulin, and thus IAPP
      is believed to be one of the factors involved in the transition from early to
      later stages of type II diabetes. Using variants of IAPP that are combinations of
      toxic or non-toxic and amyloidogenic or nonamyloidogenic forms, we have shown
      that formation of amyloid fibers is a sufficient but not necessary condition for
      the disruption of beta-cells. Instead, the ability to induce membrane disruption
      in model membranes appears to be related to the peptide's ability to stabilize
      curvature in the membrane, which in turn is related to the depth of penetration
      in the membrane.  Although many similarities exist between IAPP and other
      amyloidogenic proteins, one important difference appears to be the role of small
      oligomers in the assembly process of amyloid fibers. In many amyloidogenic
      proteins, small oligomers form a distinct metastable intermediate that is
      frequently the most toxic species; however, in IAPP, small oligomers appear to be
      transient and are rapidly converted to amyloid fibers. Moreover, the aggregation
      and toxicity of IAPP is controlled by other cofactors present in the secretory
      granule from which it is released, such as zinc and insulin, in a control
      mechanism that is somehow unbalanced in type II diabetics. Investigations into
      this process are likely to give clues to the mysterious origins of type II
      diabetes at the molecular level.

PMID- 21942865
TI  - Natural and social disasters: racial inequality in access to contraceptives after
      Hurricane Ike.
AB  - BACKGROUND: Few data are available on access to contraception following a natural
      disaster. The current study extends the literature by examining access to various
      types of birth control in a large sample of women from diverse backgrounds
      following Hurricane Ike, which made landfall on September 13, 2008, on the upper
      Texas Gulf Coast. METHODS: We examined Hurricane Ike's influence on access to
      contraceptives through survey results from 975 white, black, and Hispanic women
      16-24 years of age receiving care at one of five publicly funded reproductive
      health clinics in the Texas Gulf Coast region between August 2008 and July 2010.
      RESULTS: Overall, 13% of women reported difficulties accessing contraception.
      Black women had more difficulty than their white (p<0.001) and Hispanic (p=0.019)
      counterparts. Using multivariate analysis, we found that although family planning
      clinics in the area were open, black women (odds ratio [OR] 2.25, 95% confidence
      interval [CI] 1.37-3.73; p=0.001] and hurricane evacuees (OR 2.17, 95% CI 1.27
      3.72; p=0.005) reported greater difficulty in accessing birth control. Last, we
      found that a lack of access to birth control was related to having a higher
      frequency of unprotected sex for women of all races (p=0.001). CONCLUSIONS:
      Access to resources is critical in differentiating the level of impact of
      disasters on various groups of people. We suggest a community-based disaster
      preparedness and response model that takes women's reproductive needs into
      account.

PMID- 21942866
TI  - Disparities in screening mammography services by race/ethnicity and health
      insurance.
AB  - BACKGROUND: Black and Hispanic women are diagnosed at a later stage of breast
      cancer than white women. Differential access to specialists, diffusion of
      technology, and affiliation with an academic medical center may be related to
      this stage disparity. METHODS: We analyzed data from a mammography facility
      survey for the metropolitan region of Chicago, Illinois, to assess in part
      whether quality breast imaging services were equally accessed by non-Hispanic
      white, non-Hispanic black, and Hispanic women and by women with and without
      private insurance. Of 49 screening facilities within the city of Chicago, 43
      facilities completed the survey, and 40 facilities representing about 149,000
      mammograms, including all major academic facilities, provided data on patient
      race/ethnicity. RESULTS: Among women receiving mammograms at the facilities we
      studied, white women were more likely than black or Hispanic women to have
      mammograms at academic facilities, at facilities that relied exclusively on
      breast imaging specialists to read mammograms, and at facilities where digital
      mammography was available (p<0.001). Women with private insurance were similarly
      more likely than women without private insurance to have mammograms at facilities
      with these characteristics (p<0.001). CONCLUSIONS: Black and Hispanic women and
      women without private insurance are more likely than white women and women with
      private insurance to obtain mammography screening at facilities with less
      favorable characteristics. A disparity in use of high-quality mammography may be
      contributing to disparities in breast cancer mortality.

PMID- 21942867
TI  - Near-infrared luminescent and magnetic cyano-bridged coordination polymers
      Nd(phen)n(DMF)m[M(CN)8] (M = Mo, W).
AB  - New cyano-bridged coordination polymers
      [Nd(phen)(2)(DMF)(2)(H(2)O)Mo(CN)(8)].2H(2)O (1) and
      [Nd(phen)(DMF)(5)M(CN)(8)].xH(2)O [M = Mo (2), W (3); phen = 1,10-phenanthroline]
      have one-dimensional structures with variable number of phenanthroline ligands.
      Compounds exhibit photoluminescence in the near-infrared region and ferromagnetic
      Nd(3+)-M(5+) interactions.

PMID- 21942868
TI  - Non-invasive brain stimulation to assess and modulate neuroplasticity in
      Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative and progressive disease related
      to a gradual decline in cognitive functions such as memory, attention, perceptual
      spatial abilities, language, and executive functions. Recent evidence has
      suggested that interventions promoting neural plasticity can induce significant
      cognitive gains especially in subjects at risk of or with mild AD. Transcranial
      magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are
      non-invasive techniques that can induce significant and long-lasting changes in
      focal and non-focal neuroplasticity. In this review, we present initial
      preliminary evidence that TMS and tDCS can enhance performance in cognitive
      functions typically impaired in AD. Also, we reviewed the initial six studies on
      AD that presented early findings showing cognitive gains such as in recognition
      memory and language associated with TMS and tDCS treatment. In addition, we
      showed that TMS has also been used to assess neuroplasticity changes in AD
      supporting the notion that cortical excitability is changed in AD due to the
      neurodegenerative process. Due to the safe profile, cost of these tools, and
      initial clinical trials results, further studies are warranted in order to
      replicate and extend the initial findings of rTMS and tDCS as cognitive enhancers
      in AD. Further trials should explore different targets of stimulation along with
      different paradigms of stimulation including combination with behavioural
      interventions.

PMID- 21942869
TI  - Microdrilled cartilage defects treated with thrombin-solidified chitosan/blood
      implant regenerate a more hyaline, stable, and structurally integrated
      osteochondral unit compared to drilled controls.
AB  - This study analyzed the long-term cartilage and subchondral bone repair of
      microdrilled defects treated with chitosan glycerol-phosphate/blood implant,
      using thrombin (Factor IIa) to accelerate in situ solidification. We also
      evaluated the cartilage repair response to six smaller microdrill holes compared
      with two larger holes. Bilateral knee trochlear cartilage defects were created in
      n=8 skeletally mature rabbits, drilled with six proximal 0.5 mm and two distal
      0.9 mm holes, then covered with in situ-solidified IIa-implants (treated) or with
      IIa-alone (control). After 6.5 months of repair, cartilage repair tissues were
      analyzed by histological scoring and histomorphometry for hyaline matrix
      characteristics and osseous integration. Subchondral repair bone was analyzed by
      3D microcomputed tomography and compared to acute defects (n=6) and intact
      trochlea (n=8). Implant-treated cartilage repair tissues had higher structural
      integrity through the entire defect (p=0.02), twofold higher percent staining for
      glycosaminoglycan (p=0.0004), and ~24% more collagen type II staining over the
      smaller drill holes (p=0.008) compared with controls. Otherwise, hole diameter
      had no specific effect on cartilage repair. The subchondral bone plate was
      partially restored in treated and control defects but less dense than intact
      trochlea, with evidence of incomplete regeneration of the calcified cartilage
      layer. More residual drill holes (p=0.054) were detected in control versus
      treated defects, and control defects with more than 40% residual holes presented
      abnormally thicker trabeculae compared with treated defects. Low osteoclast
      numbers after 6.5 months repair suggested that bone was no longer remodeling. The
      subchondral bone plate surrounding the defects exhibited a significant thickening
      compared with age-matched intact trochlea. These data suggest that debridement
      and drilling can lead to long-term subchondral bone changes outside the cartilage
      defect. Compared with drilled controls, chitosan implants solidified with
      thrombin elicited a more hyaline and structurally integrated osteochondral unit,
      features needed for long-term durability.

PMID- 21942870
TI  - Anthraceno-perylene bisimides: the precursor of a new acene.
AB  - A controlled synthesis strategy for a anthracene-fused perylene bisimide was
      developed from the cyclization of an anthracene unit pendant to a perylene
      diimide scaffold. The direct cyclization led to a zigzag molecule, while a Diels
      Alder strategy influenced the regiochemistry of cyclization to afford the linear
      precursor of a new acene.

PMID- 21942880
TI  - Chondroitin 4-O-sulfotransferase-2 regulates the number of chondroitin sulfate
      chains initiated by chondroitin N-acetylgalactosaminyltransferase-1.
AB  - Recently, it has been shown that a deficiency in ChGn-1 (chondroitin N
      acetylgalactosaminyltransferase-1) reduced the numbers of CS (chondroitin
      sulfate) chains, leading to skeletal dysplasias in mice. Although these results
      indicate that ChGn-1 regulates the number of CS chains, the mechanism mediating
      this regulation is not clear. ChGn-1 is thought to initiate CS biosynthesis by
      transferring the first GalNAc (N-acetylgalactosamine) to the tetrasaccharide in
      the protein linkage region of CS. However, in vitro chondroitin polymerization
      does not occur on the non-reducing terminal GalNAc-linkage pentasaccharide
      structure. In the present study we show that several different heteromeric enzyme
      complexes composed of different combinations of four chondroitin synthase family
      members synthesized more CS chains when a GalNAc-linkage pentasaccharide
      structure with a non-reducing terminal 4-O-sulfation was the CS acceptor. In
      addition, C4ST-2 (chondroitin 4-O-sulfotransferase-2) efficiently transferred
      sulfate from 3'-phosphoadenosine 5'-phosphosulfate to position 4 of non-reducing
      terminal GalNAc-linkage residues, and the number of CS chains was regulated by
      the expression levels of C4ST-2 and of ChGn-1. Taken together, the results of the
      present study indicate that C4ST-2 plays a key role in regulating levels of CS
      synthesized via ChGn-1.

PMID- 21942871
TI  - Exploring weak, transient protein--protein interactions in crowded in vivo
      environments by in-cell nuclear magnetic resonance spectroscopy.
AB  - Biology relies on functional interplay of proteins in the crowded and
      heterogeneous environment inside cells, and functional protein interactions are
      often weak and transient. Thus, methods that preserve these interactions and
      provide information about them are needed. In-cell nuclear magnetic resonance
      (NMR) spectroscopy is an attractive method for studying a protein's behavior in
      cells because it may provide residue-level structural and dynamic information,
      yet several factors limit the feasibility of protein NMR spectroscopy in cells;
      among them, slow rotational diffusion has emerged as the most important. In this
      paper, we seek to elucidate the causes of the dramatically slow protein tumbling
      in cells and in so doing to gain insight into how the intracellular viscosity and
      weak, transient interactions modulate protein mobility. To address these
      questions, we characterized the rotational diffusion of three model globular
      proteins in Escherichia coli cells using two-dimensional heteronuclear NMR
      spectroscopy. These proteins have a similar molecular size and globular fold but
      very different surface properties, and indeed, they show very different
      rotational diffusion in the E. coli intracellular environment. Our data are
      consistent with an intracellular viscosity approximately 8 times that of water,
      too low to be a limiting factor for observation of small globular proteins by in
      cell NMR spectroscopy. Thus, we conclude that transient interactions with
      cytoplasmic components significantly and differentially affect the mobility of
      proteins and therefore their NMR detectability. Moreover, we suggest that an
      intricate interplay of total protein charge and hydrophobic interactions plays a
      key role in regulating these weak intermolecular interactions in cells.

PMID- 21942881
TI  - Bortezomib for previously untreated multiple myeloma.
AB  - INTRODUCTION: The paradigm of antimyeloma treatment has rapidly changed since the
      introduction of the first-in-class proteasome inhibitor bortezomib and the
      immunomodulatory drugs thalidomide and lenalidomide. AREAS COVERED: This
      manuscript discusses the most recent data on the frontline use of bortezomib and
      bortezomib-based combinations in multiple myeloma. Preclinical data,
      pharmacokinetics and pharmacodynamics of bortezomib are summarized, as well as
      published clinical trials of its use as a first-line treatment for transplant
      eligible and elderly myeloma patients. Additionally, the use of bortezomib in
      particular myeloma subgroups, including patients with high-risk cytogenetics and
      renal insufficiency, is discussed. Finally, the prevention and management of
      bortezomib-induced side effects, including the latest data on weekly dosing for
      untreated elderly patients, is focused on. EXPERT OPINION: Bortezomib has become
      an important backbone of frontline myeloma treatment. Nevertheless, continued
      efforts to implement newer dosing regimens and to identify new partner drugs for
      bortezomib remain an important challenge.

PMID- 21942882
TI  - Structure of the major O-specific polysaccharide from the lipopolysaccharide of
      Pseudomonas fluorescens BIM B-582: identification of 4-deoxy-D-xylo-hexose as a
      component of bacterial polysaccharides.
AB  - A novel constituent of bacterial polysaccharides, 4-deoxy-D-xylo-hexose (D
      4dxylHex), was found in the major O-specific polysaccharide from the
      lipopolysaccharide of Pseudomonas fluorescens BIM B-582. D-4dxylHex was isolated
      in the free state by paper chromatography after full acid hydrolysis of the
      polysaccharide and identified by GLC-mass spectrometry, 1H and 13C NMR
      spectroscopy, and specific rotation. It occurs as a lateral substituent in ~40%
      of the oligosaccharide repeating units, making the polysaccharide devoid of
      strict regularity. The structure of the polysaccharide was established by sugar
      analysis, Smith degradation, and two-dimensional 1H and 13C NMR spectroscopy. In
      addition, a minor polysaccharide was isolated from the same lipopolysaccharide
      and found to contain 4-O-methylrhamnose.

PMID- 21942883
TI  - Development of a measurement technique for ion distribution in an extended
      nanochannel by super-resolution-laser-induced fluorescence.
AB  - Ion behavior confined in extended nanospace (10(1)-10(3) nm) is important for
      nanofluidics and nanochemistry with dominant surface effects. In this paper, we
      developed a new measurement technique of ion distribution in the nanochannel by
      super-resolution-laser-induced fluorescence. Stimulated emission depletion
      microscopy was used to achieve a spatial resolution of 87 nm higher than the
      diffraction limit. Fluorescein was used for ratiometric measurement of pH with
      two excitation wavelengths. The pH profile in a 2D nanochannel of 410 nm width
      and 405 nm depth was successfully measured at an uncertainty of 0.05. The excess
      protons, showing lower pH than the bulk, nonuniformly distributed in the
      nanochannel to cancel the negative charge of glass wall, especially when the
      electric double layer is thick compared to the channel size. The present study
      first revealed the ion distribution near the surface or in the nanochannel, which
      is directly related to the electric double layer. In addition, the obtained
      proton distribution is important to understand the nanoscale water structure
      between single molecules and continuum phase. This technique will greatly
      contribute to understanding the basic science in nanoscale and interfacial
      dynamics, which are strongly required to develop novel miniaturized systems for
      biochemical analysis and further applications.

PMID- 21942884
TI  - Human traumatic brain injury alters circulating L-arginine and its metabolite
      levels: possible link to cerebral blood flow, extracellular matrix remodeling,
      and energy status.
AB  - Altered cerebral blood flow, cell-matrix interactions, and energy metabolism are
      secondary pathologies contributing to outcome after traumatic brain injury (TBI).
      Because L-arginine serves as the precursor for metabolites that are critical to
      these processes, we measured their plasma levels using LC-MS/GC-MS. Samples were
      collected from healthy volunteers (n=20), and patients with mild TBI (n=18),
      severe TBI (n=20), or orthopedic injury without a TBI (n=15), within the first 24
      hours of injury. Severe TBI levels of L-arginine, citrulline, ornithine, and
      hydroxyproline were significantly reduced compared to the other groups. In
      contrast, the levels of plasma creatine were significantly increased in severe
      TBI patients compared to healthy volunteers and orthopedic injury subjects. Of
      interest, the levels of creatine were found to be higher in severe TBI patients
      (GCS score <=8) whose intracranial pressure (ICP) remained below 25 mm Hg
      throughout the 5-day monitoring period, compared to TBI patients (GCS score <=8)
      who subsequently developed elevated ICP (>=25 mm Hg). The changes in L-arginine
      and its metabolite levels were not detected in subjects with mild TBI. The
      altered levels of arginine and its metabolites may contribute to secondary
      pathologies following severe TBI, and plasma levels of creatine may have
      prognostic value in identifying patients at risk for ICP elevation.

PMID- 21942885
TI  - Purification and characterization of fructan and fructansucrase from
      Lactobacillus fermentum AKJ15 isolated from Kodo ko jaanr, a fermented beverage
      from north-eastern Himalayas.
AB  - Fructansucrase and fructan produced from Lactobacillus fermentum AKJ15 were
      isolated from seeds of Kodo ko jaanr, a fermented mild-alcoholic beverage
      prepared in North East India. The strain was identified by 16S rRNA gene sequence
      analysis and biochemical characterization. The strain displayed maximum
      fructansucrase activity of 4.3 U/ml (1.02 U/mg) at 28 degrees C at 180 rpm. The
      enzyme purified by polyethylene glycol-400 gave specific activity of 5 U/mg and
      showed 90 kDa band on non-denaturing Sodium Dodecyl Sulphate-Poly Acrylamide Gel
      Electrophoresis (SDS-PAGE). The purified enzyme confirmed the presence of fructan
      by periodic acid Schiff's staining which showed magenta colour bands with both
      sucrose and raffinose. The strain produced 10.2 mg/ml fructan in broth under
      optimized culture conditions. The purified fructansucrase displayed V(max) of
      5.42 U/mg and K(m) of 16.65 mM. The enzyme showed maximum activity at 30 degrees
      C and at pH 5. The structure of fructan was analysed by (1)H and (13)C NMR
      spectra confirming beta-(2-1) and beta-(2-6) linkages.

PMID- 21942893
TI  - Density functional theory study of the carbonyl-ene reaction of encapsulated
      formaldehyde in Cu(I), Ag(I), and Au(I) exchanged FAU zeolites.
AB  - Carbonyl-ene reactions, which involve C-C bond formation, are essential in many
      chemical syntheses. The formaldehyde-propene reaction catalyzed by several of the
      group 11 metal cations, Cu(+), Ag(+), and Au(+) exchanged on the faujasite
      zeolite (metal-FAU) has been investigated by density functional theory at the M06
      L/6-31G(d,p) level. The Au-FAU exhibits a higher activity than the others due to
      the high charge transfer between the Au and the reactant molecules, even though
      it is located at a negatively charged site of the zeolite. This site enables it
      to compensate for the charge of the Au(+) ion. The NBO analysis reveals that the
      6s orbital of the Au atom plays an important role, inducing a charge on the probe
      molecules. Moreover, the effect of the zeolite framework makes the Au-FAU more
      active than the others by stabilizing the high charge induced transition
      structure. The activation energy of the reaction catalyzed by Au-FAU is 13.0
      kcal/mol whereas that of Cu and Ag-FAU is found to be around 17 kcal/mol. The
      product desorption needs to be improved for Au-FAU; however, we suggest that
      catalysts with high charge transfer might provide a promising activity.

PMID- 21942894
TI  - Usual and virtual reality video game-based physiotherapy for children and youth
      with acquired brain injuries.
AB  - Little is known about how therapists promote learning of functional motor skills
      for children with acquired brain injuries. This study explores physiotherapists'
      description of these interventions in comparison to virtual reality (VR) video
      game-based therapy. Six physiotherapists employed at a children's rehabilitation
      center participated in semi-structured interviews, which were transcribed and
      analyzed using thematic analysis. Physiotherapists describe using interventions
      that motivate children to challenge performance quality and optimize real-life
      functioning. Intervention strategies are influenced by characteristics of the
      child, parent availability to practice skills outside therapy, and therapist
      experience. VR use motivates children to participate, but can influence therapist
      use of verbal strategies and complicate interventions. Physiotherapists consider
      unique characteristics of this population when providing interventions that
      promote learning of motor skills. The VR technology has advantageous features but
      its use with this population can be challenging; further research is recommended.

PMID- 21942895
TI  - Proposed criteria for sorting examined properties in clinical laboratory reports.
AB  - To date not much importance has been given to the sorting of examined properties
      ("tests") in clinical laboratory reports. The present article contains a proposal
      about sorting the examined properties of clinical laboratory reports, in order to
      facilitate their interpretation to the requesting physicians. This proposal is
      mainly based on clinical and patho-physiological criteria. A set of groups of
      properties has been established according to the main clinical indications of
      each property. Some of these properties have several clinical indications and,
      consequently, have been included in more than one group. Some of these groups
      have been associated to other groups, so that the properties conforming them will
      always appear consecutively, since they are patho-physiologically related.
      Finally, an association between each group with the different medical
      specialities or areas of knowledge has been made, according to the clinical
      indications of each property. The groups of properties proposed are in
      concordance with their main clinical indications and their patho-physiological
      relationship. This ordering system gives priority, first, to the alarm (critical)
      values and, second, to the medical speciality or knowledge area of the requesting
      physician. This proposal can help the requesting physician to see first of all
      the most relevant clinical laboratory information related to her/his patient.

PMID- 21942896
TI  - Total synthesis of (+/-)-streptonigrin: de novo construction of a
      pentasubstituted pyridine using ring-closing metathesis.
AB  - The synthesis of the potent antitumor agent (+/-)-streptonigrin has been achieved
      in 14 linear steps and 11% overall yield from ethyl glyoxalate. The synthesis
      features a challenging ring-closing metathesis reaction, followed by elimination
      and aromatization, to furnish a key pentasubstituted pyridine fragment.

PMID- 21942897
TI  - Modulation of motor learning and memory formation by non-invasive cortical
      stimulation of the primary motor cortex.
AB  - Transcranial magnetic (TMS) and direct current (tDCS) stimulation are non
      invasive brain stimulation techniques that allow researchers to purposefully
      modulate cortical excitability in focal areas of the brain. Recent work has
      provided preclinical evidence indicating that TMS and tDCS can facilitate motor
      performance, motor memory formation, and motor skill learning in healthy subjects
      and possibly in patients with brain lesions. Although the optimal stimulation
      parameters to accomplish these goals remain to be determined, and controlled
      multicentre clinical studies are lacking, these findings suggest that cortical
      stimulation techniques could become in the future adjuvant strategies in the
      rehabilitation of motor deficits. The aim of this article is to critically review
      these findings and to discuss future directions regarding the possibility of
      combining these techniques with other interventions in neurorehabilitation.

PMID- 21942898
TI  - New series of triply bridged dinuclear Cu(II) compounds: synthesis, crystal
      structure, magnetic properties, and theoretical study.
AB  - Five new triply bridged dinuclear Cu(II) compounds have been synthesized, and
      their magnetic properties have been measured and characterized. The magnetic
      coupling constants (J) of these compounds plus a previously structurally
      characterized compound of the same type have been derived by appropriate fitting
      of the experimentally measured molar susceptibility variation with the
      temperature. Two of the compounds are ferromagnetically coupled, and three are
      antiferromagnetically coupled with J values in the [+150, -40] cm(-1) range. The
      validity of the structural aggregate Addison's parameter as a qualitative magneto
      structural correlation is confirmed. The origin of the magnetic interactions and
      the magnitude of the magnetic coupling have been analyzed by means of density
      functional theory-based calculations using a variety of state of the art exchange
      correlation potentials. It is shown that the long-range separated LC-omegaPBE
      provides the overall best agreement with experiment for this family as well as
      for a set of previously reported hetero triply bridged dinuclear Cu(II)
      compounds, especially for ferromagnetic systems.

PMID- 21942899
TI  - Multiple bases for young and older adults' judgments of learning in multitrial
      learning.
AB  - Prior work has suggested that participants use a memory-for-past-tests (MPT)
      heuristic for judgments of learning (JOLs) in a multitrial learning scenario.
      That is, when learning the same material in multiple sessions, previous memory
      performance can be used as a basis for later memory predictions. We explored this
      issue by evaluating the impact of healthy aging on the use of MPT across trials.
      Young adults and healthy older adults learned pairs of words, made JOLs, and
      received a memory test in three study-test trials on the same material. Results
      indicated that both young and older adults relied on MPT as a basis for JOLs and
      changes in MPT across trials were nominal. Further, only the most-recent past
      test influenced JOLs, whereas earlier tests were unrelated to later judgments.
      JOLs were also influenced by prior-trial JOLs and were related to subsequent
      memory performance on the same trial. We suggest that these data support both
      indirect- and direct-memory mechanisms as the bases for the MPT heuristic.
      Further, in a multitrial learning scenario, in which the same information was
      being learned, young and older adults used the same bases for their JOLs.

PMID- 21942900
TI  - Do subjective measures of attention and memory predict actual performance?
      Metacognition in older couples.
AB  - Older individuals who recognize their cognitive difficulties are more likely to
      adjust their everyday life to their actual cognitive functioning, particularly
      when they are able to estimate their abilities accurately. We assessed self- and
      spouse-ratings of memory and attention difficulties in everyday life of healthy,
      older individuals and compared them with the respective test performance. Eighty
      four older individuals (women's age, M = 67.4 years, SD = 5.2; men's age, M =
      68.5 years, SD = 4.9) completed both the self and the spouse versions of the
      Attention Deficit Questionnaire and the Everyday Memory Questionnaire and
      completed two neuropsychological tests. Using the residual score approach,
      subjective metacognitive measures of memory and attention were created and
      compared with actual test performance. Significant associations between
      subjective and objective scores were found only for men and only for episodic
      memory measures. Men who underreported memory difficulties performed more poorly;
      men who overreported memory difficulties performed better. Men's recognition
      performance was best predicted by subjective measures (R2 = .25), followed by
      delayed recall (R2 = .14) and forgetting rate (R2 = .13). The results indicate
      gender-specific differences in metacognitive accuracy and predictive validity of
      subjective ratings.

PMID- 21942911
TI  - Performance assessment of semiempirical molecular orbital methods in describing
      halogen bonding: quantum mechanical and quantum mechanical/molecular mechanical
      molecular dynamics study.
AB  - The performance of semiempirical molecular-orbital methods--MNDO, MNDO-d, AM1,
      RM1, PM3 and PM6--in describing halogen bonding was evaluated, and the results
      were compared with molecular mechanical (MM) and quantum mechanical (QM) data.
      Three types of performance were assessed: (1) geometrical optimizations and
      binding energy calculations for 27 halogen-containing molecules complexed with
      various Lewis bases (Two of the tested methods, AM1 and RM1, gave results that
      agree with the QM data.); (2) charge distribution calculations for halobenzene
      molecules, determined by calculating the solvation free energies of the molecules
      relative to benzene in explicit and implicit generalized Born (GB) solvents (None
      of the methods gave results that agree with the experimental data.); and (3)
      appropriateness of the semiempirical methods in the hybrid quantum
      mechanical/molecular-mechanical (QM/MM) scheme, investigated by studying the
      molecular inhibition of CK2 protein by eight halobenzimidazole and -benzotriazole
      derivatives using hybrid QM/MM molecular-dynamics (MD) simulations with the
      inhibitor described at the QM level by the AM1 method and the rest of the system
      described at the MM level. The pure MM approach with inclusion of an extra point
      of positive charge on the halogen atom approach gave better results than the
      hybrid QM/MM approach involving the AM1 method. Also, in comparison with the pure
      MM-GBSA (generalized Born surface area) binding energies and experimental data,
      the calculated QM/MM-GBSA binding energies of the inhibitors were improved by
      replacing the G(GB,QM/MM) solvation term with the corresponding G(GB,MM) term.

PMID- 21942913
TI  - New strategies for the development of H5N1 subtype influenza vaccines: progress
      and challenges.
AB  - The emergence and spread of highly pathogenic avian influenza (H5N1) viruses
      among poultry in Asia, the Middle East, and Africa have fueled concerns of a
      possible human pandemic, and spurred efforts towards developing vaccines against
      H5N1 influenza viruses, as well as improving vaccine production methods. In
      recent years, promising experimental reverse genetics-derived H5N1 live
      attenuated vaccines have been generated and characterized, including vaccines
      that are attenuated through temperature-sensitive mutation, modulation of the
      interferon antagonist protein, or disruption of the M2 protein. Live attenuated
      influenza virus vaccines based on each of these modalities have conferred
      protection against homologous and heterologous challenge in animal models of
      influenza virus infection. Alternative vaccine strategies that do not require the
      use of live virus, such as virus-like particle (VLP) and DNA-based vaccines, have
      also been vigorously pursued in recent years. Studies have demonstrated that
      influenza VLP vaccination can confer homologous and heterologous protection from
      lethal challenge in a mouse model of infection. There have also been improvements
      in the formulation and production of vaccines following concerns over the threat
      of H5N1 influenza viruses. The use of novel substrates for the growth of vaccine
      virus stocks has been intensively researched in recent years, and several
      candidate cell culture-based systems for vaccine amplification have emerged,
      including production systems based on Madin-Darby canine kidney, Vero, and PerC6
      cell lines. Such systems promise increased scalability of product, and reduced
      reliance on embryonated chicken eggs as a growth substrate. Studies into the use
      of adjuvants have shown that oil-in-water-based adjuvants can improve the
      immunogenicity of inactivated influenza vaccines and conserve antigen in such
      formulations. Finally, efforts to develop more broadly cross-protective
      immunization strategies through the inclusion of conserved influenza virus
      antigens in vaccines have led to experimental vaccines based on the influenza
      hemagglutinin (HA) stem domain. Such vaccines have been shown to confer
      protection from lethal challenge in mouse models of influenza virus infection.
      Through further development, vaccines based on the HA stem have the potential to
      protect vaccinated individuals against unanticipated pandemic and epidemic
      influenza virus strains. Overall, recent advances in experimental vaccines and in
      vaccine production processes provide the potential to lower mortality and
      morbidity resulting from influenza infection.

PMID- 21942914
TI  - Effect of treatment with natalizumab on ability to work in people with multiple
      sclerosis: productivity gain based on direct measurement of work capacity before
      and after 1 year of treatment.
AB  - BACKGROUND: Sweden is a high endemic region for multiple sclerosis (MS), a
      neurologic disorder characterized by repeated inflammatory episodes affecting the
      CNS. The disease has its peak age of onset at approximately 30 years and affects
      women twice as often as men. The young age of onset makes MS one of the major
      causes of reduced capacity to work due to neurologic disease in Western society.
      Natalizumab (Tysabri(r)) is among the new generation of biologic drugs for the
      treatment of MS. Clinical studies have demonstrated that natalizumab is an
      effective treatment for preventing relapses and inflammatory activity. OBJECTIVE:
      The aim of the study was to estimate the monetary value of treatment with
      natalizumab on the ability to work in patients with MS in Sweden, based on a
      direct measurement of weekly hours worked before and after 1 year of treatment
      with natalizumab. METHODS: A sample of patients, consisting of all patients who
      had started treatment with natalizumab during the period June 2007-May 2008, was
      identified through the Swedish Multiple Sclerosis Register (SMSreg). Data about
      sex, age, disease severity, and disease duration were collected from the
      register. Data about type of work and work capacity (number of hours worked per
      week) were collected retrospectively through a postal questionnaire. The average
      hours worked per week was estimated at baseline (2 weeks before treatment
      started) and at follow-up (50 weeks after treatment started), and the change was
      assigned an economic value using the human capital approach. RESULTS: This study
      showed that after 50 weeks of treatment with natalizumab, people with MS
      increased their productivity by 3.3 hours per week on average (p < 0.01), which
      corresponded to an economic value of &U20AC;3216 per person per year (year 2007
      values). A shorter duration of illness or being 25-35 years old was significantly
      associated with a greater productivity gain (p = 0.025 and p = 0.002,
      respectively). CONCLUSION: A shorter duration of illness and a lower age at the
      start of treatment were significantly associated with a greater productivity gain
      after 50 weeks of treatment with natalizumab, which indicates that it is more
      beneficial to initiate efficient therapy early in patients with MS.

PMID- 21942912
TI  - Advances in liver cancer antibody therapies: a focus on glypican-3 and
      mesothelin.
AB  - Liver cancer is one of the most common malignancies worldwide. Hepatocellular
      carcinoma (HCC) and cholangiocarcinoma (CCA) are the two most common primary
      liver cancers, yet there have been no significant advances in effective
      therapeutics. There is an urgent need to identify molecular targets for the
      development of novel therapeutic approaches. In this review, glypican-3 (GPC3)
      and mesothelin are discussed, with a focus on their potential as targets for
      antibody therapy in liver cancer. GPC3 and mesothelin are
      glycosylphosphatidylinositol-anchored proteins present on the cell surface. They
      are attractive candidates for liver cancer therapy given that GPC3 and mesothelin
      show high expression in HCC and CCA, respectively. Antibody drugs targeting GPC3
      or mesothelin have shown anti-cancer activity in mice. Humanized or chimeric IgG
      molecules based on first-generation murine monoclonal antibodies against these
      antigens are being evaluated in clinical studies. Recently, fully human
      monoclonal antibodies against GPC3 and mesothelin have been isolated by antibody
      phage display technology that may provide opportunities for novel cancer therapy.

PMID- 21942915
TI  - Sunitinib: in advanced, well differentiated pancreatic neuroendocrine tumors.
AB  - Sunitinib inhibits several receptor tyrosine kinases involved in cancer growth,
      metastasis, and neoangiogenesis, with its active metabolite (SU012662)
      demonstrating similar potency. In a randomized, double-blind, multinational,
      phase III trial, continuous treatment with oral sunitinib 37.5 mg/day
      significantly prolonged median progression-free survival time (primary endpoint)
      ~2-fold relative to placebo in adults with locally advanced and/or metastatic,
      well differentiated pancreatic neuroendocrine tumors (pNETs). Sunitinib was also
      associated with a significantly greater objective tumor response rate than
      placebo, although limited data from an updated analysis demonstrated no
      significant difference between the treatments groups in terms of median overall
      survival. Continuous treatment with sunitinib generally had no detrimental effect
      on health-related quality of life and was generally well tolerated in patients
      with pNETs in this trial, with most adverse events being manageable and of grade
      1 or 2 severity.

PMID- 21942916
TI  - Nanofiltered human C1 inhibitor concentrate (Cinryze(r)): in hereditary
      angioedema.
AB  - Intravenous nanofiltered human C1 inhibitor (C1-INH NF) concentrate (Cinryze(r))
      is used as a direct replacement of deficient levels of plasma C1 inhibitor in
      patients with hereditary angioedema (HAE). In the EU, C1-INH NF concentrate 1000
      U is indicated in the treatment, pre-procedural prevention, and routine
      prevention of angioedema attacks in adults and adolescents with HAE. Intravenous
      C1-INH NF concentrate 1000 U effectively relieved angioedema attacks in patients
      with HAE. In a randomized, double-blind trial in pediatric and adult patients,
      the median time to onset of unequivocal relief from an attack was significantly
      shorter with C1-INH NF concentrate than with placebo. In an open-label trial,
      both unequivocal relief and clinical relief were shown in the majority of attacks
      within 1 and 4 hours of infusion of C1-INH NF concentrate, regardless of the site
      (i.e. gastrointestinal, cutaneous, laryngeal, or genitourinary) of the defining
      symptom. When administered prior to a procedure, open-label intravenous C1-INH NF
      concentrate 1000 U reduced the incidence of angioedema attacks during and after a
      variety of dental, surgical, or interventional diagnostic procedures in pediatric
      and adult patients with HAE. Routine preventative treatment with intravenous C1
      INH NF concentrate 1000 U every 3 or 4 days reduced the number of angioedema
      attacks. In a randomized, double-blind, crossover trial in pediatric and adult
      patients with HAE, the mean normalized number of attacks per 12-week period was
      significantly lower during routine prevention with C1-INH NF concentrate than
      with placebo. Routine prevention with C1-INH NF concentrate reduced the median
      monthly attack rate from baseline in an open-label trial. Intravenous C1-INH NF
      concentrate was well tolerated in clinical trials in patients with HAE. No cases
      of viral transmission were reported.

PMID- 21942917
TI  - Rituximab as first-line maintenance therapy following rituximab-containing
      therapy for follicular lymphoma: profile report.

PMID- 21942918
TI  - Spotlight on lenalidomide in relapsed or refractory multiple myeloma.
AB  - In several countries, including the US and in Europe, oral lenalidomide in
      combination with oral dexamethasone is approved for the treatment of multiple
      myeloma patients (aged >=18 years) who have received at least one prior
      antimyeloma therapy. The key therapeutic mechanisms of action of lenalidomide (a
      thalidomide analog) reside in its immunomodulatory, antiproliferative, and anti
      angiogenic properties. In patients with multiple myeloma, lenalidomide has dual
      effects, exerting a direct antitumor response by inhibiting proliferation and by
      inducing apoptosis of tumor cells. Lenalidomide also acts to enhance the immune
      system by inducing the activation of immune effector cells, such as T cells and
      natural killer cells, and inducing cytokine production. In the pivotal MM-009 and
      MM-010 phase III registration trials, treatment with lenalidomide plus
      dexamethasone was effective and had a manageable safety and tolerability profile
      in relapsed or refractory patients with multiple myeloma. In robust
      pharmacoeconomic analyses based on these trials, relative to dexamethasone,
      lenalidomide plus dexamethasone treatment met the assumed willingness-to-pay
      threshold for cost effectiveness from the UK and Scottish healthcare payer
      perspective in this patient population. The UK National Institute for Health and
      Clinical Excellence and the Scottish Medicines Consortium considered that the
      health economic case for lenalidomide plus dexamethasone treatment was
      demonstrated for patients who had received at least two prior antimyeloma
      therapies. In addition, in pharmacoeconomic analyses based on indirect
      comparisons of clinical efficacy, regulatory agencies in Norway and Sweden
      considered that lenalidomide plus dexamethasone treatment was cost effective
      relative to bortezomib in patients who have received at least one prior
      antimyeloma therapy. Furthermore, compared with placebo plus dexamethasone,
      treatment with lenalidomide plus dexamethasone significantly prolonged the median
      time to progression, increased overall response rates and prolonged overall
      survival, with significantly longer median time to progression and overall
      response rates observed for all subgroups of patients. Thus, combination therapy
      with lenalidomide plus dexamethasone provides a valuable option for the treatment
      of relapsed or refractory adult patients with multiple myeloma.

PMID- 21942919
TI  - Spotlight on quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant
      vaccine(Gardasil(r)) in the prevention of premalignant genital lesions, genital
      cancer, and genital warts in women.
AB  - Quadrivalent human papilloma virus (HPV) [types 6, 11, 16, 18] recombinant
      vaccine (Gardasil(r); Silgard(r)) is composed of virus-like particles (VLPs)
      formed by self-assembly of recombinant L1 capsid protein from each of HPV types
      6, 11, 16, and 18. The VLPs are noninfectious, containing no DNA, and are highly
      immunogenic, inducing high levels of neutralizing antibodies against the
      particular HPV types when administered to animals or humans. Quadrivalent HPV
      vaccine is indicated for use from the age of 9 years for the prevention of
      premalignant genital lesions (cervical, vulvar, and vaginal), cervical cancer,
      and external genital warts (condyloma acuminata) causally related to certain
      oncogenic or specific HPV types. In placebo-controlled clinical trials,
      quadrivalent HPV vaccine administered as three doses over 6 months provided high
      level protection against infection or disease caused by the vaccine HPV types
      over 2-4 years of follow-up in females aged 15-45 years who were naive to the
      vaccine HPV types. A degree of cross-protection against certain other non-vaccine
      high-risk HPV types was also observed. The vaccine is not effective against
      current infection with a vaccine HPV type. Girls or women with current infection
      with one or more of the vaccine HPV types gained protection from infection or
      disease caused by the remaining vaccine HPV types and they were also protected
      against reinfection with the same HPV type after clearance of an infection caused
      by a vaccine HPV type. High seroconversion rates and high levels of anti-HPV
      antibodies were observed in all vaccinated individuals of all age ranges from 9
      to 45 years. No correlation was found between antibody levels and protective
      efficacy of the vaccine. Rechallenge with quadrivalent HPV vaccine produced a
      potent anamnestic humoral immune response. The vaccine is generally well
      tolerated and is projected to be cost effective in most pharmacoeconomic models.
      Therefore, quadrivalent HPV vaccine offers an effective means, in combination
      with screening programs, to substantially reduce the burden of HPV-related
      precancerous lesions and cancer, particularly cervical cancer, as well as
      anogenital warts.

PMID- 21942920
TI  - Biofortification of tomato (Solanum lycopersicum) fruit with the anticancer
      compound methylselenocysteine using a selenocysteine methyltransferase from a
      selenium hyperaccumulator.
AB  - Methylselenocysteine (MeSeCys) is an amino acid derivative that possesses potent
      anticancer activity in animals. Plants that can tolerate growth on soils with
      high Se content, known as Se hyperaccumulators, do so by converting inorganic Se
      to MeSeCys by the enzyme selenocysteine methyltransferase (SMT). A cDNA encoding
      the SMT from a Se hyperaccumulator was overexpressed in tomato (Solanum
      lycopersicum). Transgenic plants were provided with selenite or selenate to the
      roots during fruit development, and liquid chromatography-mass spectrometry was
      used to show that MeSeCys accumulated in the fruit but not in the leaves.
      Depending on the transgenic line and Se treatment, up to 16% of the total Se in
      the fruit was present as MeSeCys. MeSeCys was produced more effectively from
      selenite on a percentage conversion basis, but greater accumulation of MeSeCys
      could be achieved from selenate due to its better translocation from the roots.
      MeSeCys was heat stable and survived processing of the fruit to tomato juice.

PMID- 21942922
TI  - Sustained overexpression of CYP1A1 and 1B1 and steady accumulation of DNA adducts
      by low-dose, continuous exposure to benzo[a]pyrene by polymeric implants.
AB  - Many carcinogenesis and tumorigenesis studies reported in the past several
      decades have relied upon bolus dose(s) of test compounds to determine their DNA
      damage and carcinogenic potential. The high doses are far from the human scenario
      where exposure is almost always to low doses and for long duration. In this
      study, we report a novel polymeric implant system that provides continuous
      ("24/7") exposure to low doses using benzo[a]pyrene (BP) as a model carcinogen.
      Cylindrical implants (1 cm length, 3.2 mm diameter; 10 mg BP/100 mg implant)
      prepared from polycaprolactone:F68 (9:1) showed controlled release in vitro for
      long duration. To determine the rate of release and biochemical effects in vivo,
      groups of female Sprague-Dawley rats received either no treatment or subcutaneous
      sham or BP implants (1 cm, 10% load) and were euthanized after 6, 15, 30, and 180
      days; the average dose of BP by the implant route was 16.7 +/- 3 MUg/rat. For
      comparison, rats were also treated with a single bolus dose of BP
      intraperitoneally (10 mg/rat) and euthanized at 6, 15, and 30 days. DNA adducts
      analyzed by (32)P-postlabeling in the lung and liver increased steadily with time
      with levels reaching 31 +/- 3 and 17 +/- 6 adducts/10(9) nucleotides,
      respectively, after 25 weeks; the adduct burden in the mammary tissue initially
      increased but then declined with time presumably due to high cell turn over. In
      contrast, the bolus dose treatment showed the highest DNA adduct levels after 6
      days, followed by a steady decline. The steady accumulation of tissue DNA adducts
      in the implant groups corroborates the sustained overexpression of CYP1A1 and
      1B1, the cytochrome P450s involved in the conversion of BP to its electrophilic
      metabolites. In contrast, the overexpression of CYP1A1 and 1B1 resulting from the
      bolus dose of BP lasted only for a few days. This is the first demonstration
      revealing that low-dose, continuous exposure to environmental polycyclic aromatic
      hydrocarbons such as BP can render sustained expression of CYPs and steady
      accumulation of tissue DNA adducts. On the basis of our recent study in which we
      showed the presence of 17beta-estradiol in the lung, the sustained overexpression
      of CYP1A1 and 1B1 due to continuous exposure to BP may increase the
      susceptibility to estrogen-mediated carcinogenicity.

PMID- 21942921
TI  - Granule size-dependent bone regenerative capacity of octacalcium phosphate in
      collagen matrix.
AB  - The present study was designed to determine whether the osteoconductivity of
      octacalcium phosphate-collagen (OCP/Col) composite can be improved by controlling
      the granule size of OCP. The granules of synthetic OCP, with diameters in the
      range of 53 to 300, 300 to 500, and 500 to 1000 MUm, were used as an inorganic
      source of composite materials mixed with atelo-Col. After vacuum dehydrothemal
      treatment, OCP/Col disks were implanted into critical-sized calvaria defects in
      Wistar rats for 4, 8, and 12 weeks and examined radiographically, histologically,
      histomorphometrically, and histochemically. The materials were characterized
      according to mercury intrusion porosimetry and scanning electron microscopy. X
      ray diffraction was performed before and after implantation. The dissolution of
      OCP crystals in a Col matrix was determined by immersing OCP/Col disks in a
      culture medium. OCP/Col had a constant pore size (~30 MUm) regardless of OCP
      granule size. OCP in the Col matrix tended to convert to hydroxyapatite (HA)
      during the implantation. OCP/Col with the smallest granules of OCP enhances both
      bone regeneration and biodegradation the most through tartrate-resistant acid
      phosphatase (TRAP)-positive osteoclastic cellular resorption of OCP granules. The
      smallest OCP granules in the Col matrix showed the highest dissolution and had
      the greatest potential to form HA. The results indicated that the size of the
      included OCP granules can controll the osteoconductivity of OCP/Col. The overall
      results suggest that the physicochemical property of OCP crystals is a factor
      that determines the bone regenerative capacity of OCP/Col in critical-sized
      calvaria large bone defects in rats.

PMID- 21942923
TI  - Estradiol levels predict bone mineral density in male collegiate athletes: a
      pilot study.
AB  - OBJECTIVE:   Strenuous training commonly results in amenorrhoea, which
      contributes to bone loss in some female collegiate athletes. However, the impact
      of athletic training on endocrine function and bone mineral density (BMD) in male
      collegiate athletes is less well understood. The objective of the study was to
      investigate the specific endocrine determinants of BMD in male collegiate runners
      and wrestlers, including the potential impact of gonadal steroid levels. DESIGN: 
      Cross-sectional study. PATIENTS:   Twenty-six division I collegiate male
      athletes (wrestlers, runners and golfers). MEASUREMENTS:   Main outcome measures
      included (i) BMD endpoints measured by dual energy x-ray absorptiometry (DXA);
      (ii) endocrine end-points: total and free oestradiol, total and free
      testosterone; (iii) body composition end-points: lean and fat mass, measured by
      DXA; and (iv) exercise end-points: maximal oxygen uptake (VO(2) max), number of
      miles run weekly and grip strength. RESULTS:   Free and total oestradiol levels
      were important positive determinants of BMD. In contrast, total and free
      testosterone levels were not significant predictors of BMD at any skeletal site
      (except for free testosterone at the radius). In addition, lean body mass, %
      ideal body weight, total body weight, body mass index (BMI) and hours per week of
      resistance training were positive predictors of BMD. VO(2) max was a negative
      predictor of BMD. Mean BMD was higher at all skeletal sites in the wrestlers
      compared with the runners and a comparison group (golfers). CONCLUSIONS:   Our
      data suggest that oestradiol levels, BMI, and resistance training are more
      important determinants of BMD in male collegiate athletes than testosterone.

PMID- 21942924
TI  - Effects of variations in duodenal glucose load on blood pressure, heart rate,
      superior mesenteric artery blood flow and plasma noradrenaline in healthy young
      and older subjects.
AB  - PPH (postprandial hypotension), leading to increased morbidity and mortality, is
      an important clinical problem, particularly in the elderly and individuals with
      autonomic dysfunction. The magnitude of the postprandial fall in BP (blood
      pressure) appears to be dependent on the rate of nutrient entry into the small
      intestine and may be related to changes in splanchnic blood flow and sympathetic
      nerve activity. We aimed at determining the comparative effects of different ID
      (intraduodenal) glucose loads on BP, HR (heart rate), SMA (superior mesenteric
      artery) flow and vascular conductance and plasma NA (noradrenaline) in 'young'
      and 'older' subjects. A total of 12 'young' (six male and six female; age, 22.2+/
      2.3 years) and 12 'older' (six male and six female; age, 68.7+/-1.0 years)
      subjects, the latter who have been studied previously [Vanis, Gentilcore, Rayner,
      Wishart, Horowitz, Feinle-Bisset and Jones (2011) Am. J. Physiol. Regul. Integr.
      Comp. Physiol., 300, R1524-R1531], had measurements of BP, HR, SMA flow and
      plasma NA before, and during, ID infusions of glucose at 1, 2 or 3 kcal/min
      ('G1', 'G2' and 'G3') (where 1 kcal~4.184 J), or 'S' (saline) for 60 min. In
      'young' subjects, there was no change in BP during any of the four infusions. In
      contrast, in 'older' subjects, SBP (systolic BP) fell during 'G2', and 'G3'
      (P<0.005 for both), but not during 'S' or 'G1'. In 'young' and 'older' subjects
      HR increased during 'G2' (P<0.05) and 'G3' (P<0.001), a response that was greater
      (P<0.05) in the young, but not during 'S' or 'G1'. The rise in SMA flow and
      vascular conductance in response to ID glucose were load-dependent in both
      'young' and 'older' subjects (P<0.001 for all), with no difference between them.
      Plasma NA rose in response to 'G2' and 'G3' (P<0.05) in the young, but in 'G3'
      (P<0.05) only in the 'older' subjects, with no difference between them. Hence, in
      response to small intestinal glucose infusions at 1, 2 and 3 kcal/min, 'older',
      but not 'young', subjects exhibit a comparable fall in BP in response to the two
      higher glucose loads, which may reflect an inadequate, compensatory, rise in HR,
      in the 'older' subjects, but not a greater increase in SMA conductance.

PMID- 21942925
TI  - Inflammation protein SAA2.2 spontaneously forms marginally stable amyloid fibrils
      at physiological temperature.
AB  - For nearly four decades, the formation of amyloid fibrils by the inflammation
      related protein serum amyloid A (SAA) has been pathologically linked to the
      disease amyloid A (AA) amyloidosis. However, here we show that the nonpathogenic
      murine SAA2.2 spontaneously forms marginally stable amyloid fibrils at 37 
      degrees C that exhibit cross-beta structure, binding to thioflavin T, and
      fibrillation by a nucleation-dependent seeding mechanism. In contrast to the high
      stability of most known amyloid fibrils to thermal and chemical denaturation,
      experiments monitored by glutaraldehyde cross-linking/SDS-PAGE, thioflavin T
      fluorescence, and light scattering (OD(600)) showed that the mature amyloid
      fibrils of SAA2.2 dissociate upon incubation in >1.0 M urea or >45  degrees C.
      When considering the nonpathogenic nature of SAA2.2 and its ~1000-fold increased
      concentration in plasma during an inflammatory response, its extreme in vitro
      amyloidogenicity under physiological-like conditions suggest that SAA amyloid
      might play a functional role during inflammation. Of general significance, the
      combination of methods used here is convenient for exploring the stability of
      amyloid fibrils that are sensitive to urea and temperature. Furthermore, our
      studies imply that analogous to globular proteins, which can possess structures
      ranging from intrinsically disordered to extremely stable, amyloid fibrils formed
      in vivo might have a broader range of stabilities than previously appreciated
      with profound functional and pathological implications.

PMID- 21942926
TI  - A comparison of the hypoalgesic effects of transcutaneous electrical nerve
      stimulation (TENS) and non-invasive interactive neurostimulation (InterX((r))) on
      experimentally induced blunt pressure pain using healthy human volunteers.
AB  - OBJECTIVES: Non-invasive interactive neurostimulation (InterX((r))) delivers high
      amplitude electrical pulsed currents at points of low impedance on the skin. This
      study compared the hypoalgesic effect of non-invasive interactive
      neurostimulation with transcutaneous electrical nerve stimulation (TENS).
      MATERIALS AND METHODS: A repeated measures parallel group study on healthy human
      volunteers randomized to receive strong non-painful TENS or non-invasive
      interactive neurostimulation for 21 min on the forearm (N= 10/group). Pressure
      algometry was used to determine blunt pressure pain threshold at baseline, 10,
      and 20 min during stimulation, and 5 min post stimulation. RESULTS: Low impedance
      sites were found in half of the participants receiving non-invasive interactive
      neurostimulation. ANOVA found no effects for intervention (p= 0.923), time *
      intervention interaction (p= 0.21), or time (p= 0.094). CONCLUSIONS: Given the
      limited power of this study, we show that there were no significant differences
      in hypoalgesia between non-invasive interactive neurostimulation and TENS. Unlike
      our previous studies we also failed to detect a change pain threshold during
      TENS. Nevertheless, our findings can be used to inform the design of an
      appropriately powered study on pain patients.

PMID- 21942927
TI  - Thalidomide delayed the ability of 4T1 cells to amass into tumors in Balb/c mice.
AB  - Thalidomide (Thal) can suppress the growth of established, as well as explanted
      tumors in mice. We wanted to determine if it could suppress the ability of tumor
      cells to assemble and establish a primary tumor at the injection site. Using the
      mouse 4T1 mammary tumor model, we fed Thal to mice for 4 days, then injected
      10(5) 4T1 cells into the interscapular region of Balb/c mice. After 20 days on
      treatment with Thal, all seven control mice, fed with meal had tumors ranging
      from 3 to 93 mm(3) (median 20). Two of the eight mice fed with meal + Thal had no
      tumors, and the remaining mice had tumors ranging from 2 to 22 mm(3) (median 5).
      The median volume of the tumors in the control group was significantly more than
      that of mice treated with Thal (p = 0.03, Mann-Whitney test). In vitro treatment
      of the 4T1cells with Thal did not inhibit their ability to proliferate, to adhere
      to plastic, or to bind to Concanavalin-A. Thal caused a marked reduction in the
      ability of the 4T1 cells to assemble into palpable tumors.

PMID- 21942928
TI  - Increasing the use of group interventions in a pediatric rehabilitation program:
      perceptions of administrators, therapists, and parents.
AB  - OBJECTIVES: To explore perceptions related to increased utilization of group
      interventions as a part of the service reorganization within a pediatric
      rehabilitation program. METHODS: Individual interviews with program
      administrators (n = 13) and focus groups with therapists (n = 19) and parents of
      children with disabilities (n = 5) were conducted. Data were analyzed using a
      coding grid inspired by the organized action systems theory. RESULTS:
      Administrators and therapists identified several issues including the need to
      improve the referral process for groups and the coordination across services.
      Groups considerably modified practice and required substantial efforts from
      therapists. Administrators felt groups contributed to increased service
      accessibility. Although therapists had some doubts about service quality in
      groups, especially in regard to the reduced attention to individual needs, they
      reported positive benefits on children's social participation. Generally, parents
      were satisfied with group interventions. CONCLUSION: Groups appear to be a
      promising method of service delivery, but organizational-related issues should be
      considered.

PMID- 21942929
TI  - Extended-release gabapentin in post-herpetic neuralgia.
AB  - INTRODUCTION: In early 2011, the FDA gave approval to a new preparation of
      gabapentin, licensed for the treatment of post-herpetic neuralgia (PHN).
      Gabapentin is commonly used worldwide for multiple indications, which include
      neuropathic pain. The new drug combines generic gabapentin with a polymeric
      delivery system allowing for extended release and is licensed to be given only as
      a once-daily dosing regimen. AREAS COVERED: The article aims to review the
      available evidence relating to the pharmacokinetics, tolerability and efficacy of
      extended-release gabapentin (GpER). It addresses the current state of the drug's
      progress through regulation and the intention of its manufacturer for the market.
      EXPERT OPINION: Although GpER has been approved by the FDA for once-daily use in
      PHN, there is a relative paucity of data for both its efficacy and the optimum
      dosing schedule (once or twice a day). There are no data directly comparing GpER
      with the immediate-release preparation or other first-line treatments for PHN.
      Therefore, the true status of GpER as a treatment option needs to be enhanced
      with additional experimental evidence for its efficacy and favourable side-effect
      profile.

PMID- 21942930
TI  - Terminal complement inhibition decreases antibody-mediated rejection in
      sensitized renal transplant recipients.
AB  - Sensitized renal transplant recipients with high levels of donor-specific
      alloantibody (DSA) commonly develop antibody-mediated rejection (AMR), which may
      cause acute graft loss or shorten allograft survival. We examined the efficacy of
      terminal complement inhibition with the humanized anti-C5 antibody, eculizumab,
      in the prevention AMR in renal transplant recipients with a positive crossmatch
      against their living donor. The incidence of biopsy-proven AMR in the first 3
      months posttransplant in 26 highly sensitized recipients of living donor renal
      transplants who received eculizumab posttransplant was compared to a historical
      control group of 51 sensitized patients treated with a similar plasma exchange
      (PE)-based protocol without eculizumab. The incidence of AMR was 7.7% (2/26) in
      the eculizumab group compared to 41.2% (21/51) in the control group (p = 0.0031).
      Eculizumab also decreased AMR in patients who developed high levels of DSA early
      after transplantation that caused proximal complement activation. With
      eculizumab, AMR episodes were easily treated with PE reducing the need for
      splenectomy. On 1-year protocol biopsy, transplant glomerulopathy was found to be
      present in 6.7% (1/15) eculizumab-treated recipients and in 35.7% (15/42) of
      control patients (p = 0.044). Inhibition of terminal complement activation with
      eculizumab decreases the incidence of early AMR in sensitized renal transplant
      recipients (ClincalTrials.gov number NCT006707).

PMID- 21942931
TI  - Nucleosome-coupled expression differences in closely-related species.
AB  - BACKGROUND: Genome-wide nucleosome occupancy is negatively related to the average
      level of transcription factor motif binding based on studies in yeast and several
      other model organisms. The degree to which nucleosome-motif interactions relate
      to phenotypic changes across species is, however, unknown. RESULTS: We address
      this challenge by generating nucleosome positioning and cell cycle expression
      data for Saccharomyces bayanus and show that differences in nucleosome occupancy
      reflect cell cycle expression divergence between two yeast species, S. bayanus
      and S. cerevisiae. Specifically, genes with nucleosome-depleted MBP1 motifs
      upstream of their coding sequence show periodic expression during the cell cycle,
      whereas genes with nucleosome-shielded motifs do not. In addition, conserved cell
      cycle regulatory motifs across these two species are more nucleosome-depleted
      compared to those that are not conserved, suggesting that the degree of
      conservation of regulatory sites varies, and is reflected by nucleosome occupancy
      patterns. Finally, many changes in cell cycle gene expression patterns across
      species can be correlated to changes in nucleosome occupancy on motifs (rather
      than to the presence or absence of motifs). CONCLUSIONS: Our observations suggest
      that alteration of nucleosome occupancy is a previously uncharacterized feature
      related to the divergence of cell cycle expression between species.

PMID- 21942933
TI  - Quantitative tandem mass spectrometric imaging of endogenous acetyl-L-carnitine
      from piglet brain tissue using an internal standard.
AB  - Matrix-assisted laser desorption/ionization (MALDI) based mass spectrometric
      imaging (MSI) is increasingly being used as an analytical tool to evaluate the
      molecular makeup of tissue samples. From the direct analysis of a tissue section,
      the physical integrity of sample is preserved; thus, spatial information of a
      compound's distribution may be determined. One limitation of the technique,
      however, has been the inability to determine the absolute concentration from a
      tissue sample. Here we report the development of a quantitative MSI technique in
      which the distribution of acetyl-L-carnitine (AC) in a piglet brain sample is
      quantified with MALDI MSI. An isotopically labeled internal standard was applied
      uniformly beneath the tissue section, and wide-isolation tandem mass spectrometry
      was performed. Normalizing the analyte ion signal by the internal standard ion
      signal resulted in significant improvements in MS images, signal reproducibility,
      and calibration curve linearity. From the improved MS images, the concentration
      of AC was determined and plotted producing a concentration-scaled image of the
      distribution of AC in the piglet brain section.

PMID- 21942932
TI  - Cognitive and memory training in adults at risk of dementia: a systematic review.
AB  - BACKGROUND: Effective non-pharmacological cognitive interventions to prevent
      Alzheimer's dementia or slow its progression are an urgent international
      priority. The aim of this review was to evaluate cognitive training trials in
      individuals with mild cognitive impairment (MCI), and evaluate the efficacy of
      training in memory strategies or cognitive exercises to determine if cognitive
      training could benefit individuals at risk of developing dementia. METHODS: A
      systematic review of eligible trials was undertaken, followed by effect size
      analysis. Cognitive training was differentiated from other cognitive
      interventions not meeting generally accepted definitions, and included both
      cognitive exercises and memory strategies. RESULTS: Ten studies enrolling a total
      of 305 subjects met criteria for cognitive training in MCI. Only five of the
      studies were randomized controlled trials. Meta-analysis was not considered
      appropriate due to the heterogeneity of interventions. Moderate effects on memory
      outcomes were identified in seven trials. Cognitive exercises (relative effect
      sizes ranged from .10 to 1.21) may lead to greater benefits than memory
      strategies (.88 to -1.18) on memory. CONCLUSIONS: Previous conclusions of a lack
      of efficacy for cognitive training in MCI may have been influenced by not clearly
      defining the intervention. Our systematic review found that cognitive exercises
      can produce moderate-to-large beneficial effects on memory-related outcomes.
      However, the number of high quality RCTs remains low, and so further trials must
      be a priority. Several suggestions for the better design of cognitive training
      trials are provided.

PMID- 21942934
TI  - Coevolution of amino acid residues in the key photosynthetic enzyme Rubisco.
AB  - BACKGROUND: One of the key forces shaping proteins is coevolution of amino acid
      residues. Knowing which residues coevolve in a particular protein may facilitate
      our understanding of protein evolution, structure and function, and help to
      identify substitutions that may lead to desired changes in enzyme kinetics.
      Rubisco, the most abundant enzyme in biosphere, plays an essential role in the
      process of carbon fixation through photosynthesis, thus facilitating life on
      Earth. This makes Rubisco an important model system for studying the dynamics of
      protein fitness optimization on the evolutionary landscape. In this study we
      investigated the selective and coevolutionary forces acting on large subunit of
      land plants Rubisco using Markov models of codon substitution and clustering
      approaches applied to amino acid substitution histories. RESULTS: We found that
      both selection and coevolution shape Rubisco, and that positively selected and
      coevolving residues have their specifically favored amino acid composition and
      pairing preference. The mapping of these residues on the known Rubisco tertiary
      structures showed that the coevolving residues tend to be in closer proximity
      with each other compared to the background, while positively selected residues
      tend to be further away from each other. This study also reveals that the
      residues under positive selection or coevolutionary force are located within
      functionally important regions and that some residues are targets of both
      positive selection and coevolution at the same time. CONCLUSION: Our results
      demonstrate that coevolution of residues is common in Rubisco of land plants and
      that there is an overlap between coevolving and positively selected residues.
      Knowledge of which Rubisco residues are coevolving and positively selected could
      be used for further work on structural modeling and identification of
      substitutions that may be changed in order to improve efficiency of this
      important enzyme in crops.

PMID- 21942936
TI  - Network-based analysis and characterization of adverse drug-drug interactions.
AB  - Co-administration of multiple drugs may cause adverse effects, which are usually
      known but sometimes unknown. Package inserts of prescription drugs are supposed
      to contain contraindications and warnings on adverse interactions, but such
      information is not necessarily complete. Therefore, it is becoming more important
      to provide health professionals with a comprehensive view on drug-drug
      interactions among all the drugs in use as well as a computational method to
      identify potential interactions, which may also be of practical value in society.
      Here we extracted 1,306,565 known drug-drug interactions from all the package
      inserts of prescription drugs marketed in Japan. They were reduced to 45,180
      interactions involving 1352 drugs (active ingredients) identified by the D
      numbers in the KEGG DRUG database, of which 14,441 interactions involving 735
      drugs were linked to the same drug-metabolizing enzymes and/or overlapping drug
      targets. The interactions with overlapping targets were further classified into
      three types: acting on the same target, acting on different but similar targets
      in the same protein family, and acting on different targets belonging to the same
      pathway. For the rest of the extracted interaction data, we attempted to
      characterize interaction patterns in terms of the drug groups defined by the
      Anatomical Therapeutic Chemical (ATC) classification system, where the high
      resolution network at the D number level is progressively reduced to a low
      resolution global network. Based on this study we have developed a drug-drug
      interaction retrieval system in the KEGG DRUG database, which may be used for
      both searching against known drug-drug interactions and predicting potential
      interactions.

PMID- 21942935
TI  - Clinical characteristics and prognosis of osteosarcoma in young children: a
      retrospective series of 15 cases.
AB  - BACKGROUND: Osteosarcoma is the most common primary bone malignancy in childhood
      and adolescence. However, it is very rare in children under 5 years of age.
      Although studies in young children are limited in number, they all underline the
      high rate of amputation in this population, with conflicting results being
      recently reported regarding their prognosis. METHODS: To enhance knowledge on the
      clinical characteristics and prognosis of osteosarcoma in young children, we
      reviewed the medical records and histology of all children diagnosed with
      osteosarcoma before the age of five years and treated in SFCE (Societe Francaise
      des Cancers et leucemies de l'Enfant) centers between 1980 and 2007. RESULTS:
      Fifteen patients from 7 centers were studied. Long bones were involved in 14
      cases. Metastases were present at diagnosis in 40% of cases. The histologic type
      was osteoblastic in 74% of cases. Two patients had a relevant history. One child
      developed a second malignancy 13 years after osteosarcoma diagnosis.Thirteen
      children received preoperative chemotherapy including high-dose methotrexate, but
      only 36% had a good histologic response. Chemotherapy was well tolerated, apart
      from a case of severe late convulsive encephalopathy in a one-year-old infant.
      Limb salvage surgery was performed in six cases, with frequent mechanical and
      infectious complications and variable functional outcomes.Complete remission was
      obtained in 12 children, six of whom relapsed. With a median follow-up of 5
      years, six patients were alive in remission, seven died of their disease (45%),
      in a broad range of 2 months to 8 years after diagnosis, two were lost to follow
      up. CONCLUSIONS: Osteosarcoma seems to be more aggressive in children under five
      years of age, and surgical management remains a challange.

PMID- 21942937
TI  - Alzheimer's disease camouflaged by histrionic personality disorder.
AB  - A common condition in Alzheimer's disease (AD) is unawareness of deficits.
      Different concepts try to elucidate the nature of this symptom. An essential
      question relates to the interaction of organic and psychogenic factors. Here we
      present a patient who displayed her cognitive deficits as attention-seeking
      behaviour. There was a history of histrionic personality disorder according to
      ICD-10 criteria. Unexpectedly, the final diagnosis after extensive diagnostic
      work-up was AD. The unusual coincidence of AD and a histrionic personality
      disorder hampered the clinical process of diagnosing dementia. We discuss
      unawareness as a complex concept incorporating neuroanatomical, psychiatric, and
      psychosocial aspects.

PMID- 21942938
TI  - Self-reported responsiveness to direct-to-consumer drug advertising and
      medication use: results of a national survey.
AB  - ABSTRACT:  BACKGROUND: Direct-to-consumer (DTC) marketing of pharmaceuticals is
      controversial, yet effective. Little is known relating patterns of medication use
      to patient responsiveness to DTC. METHODS: We conducted a secondary analysis of
      data collected in national telephone survey on knowledge of and attitudes toward
      DTC advertisements. The survey of 1081 U.S. adults (response rate = 65%) was
      conducted by the Food and Drug Administration (FDA). Responsiveness to DTC was
      defined as an affirmative response to the item: "Has an advertisement for a
      prescription drug ever caused you to ask a doctor about a medical condition or
      illness of your own that you had not talked to a doctor about before?" Patients
      reported number of prescription and over-the-counter (OTC) medicines taken as
      well as demographic and personal health information. RESULTS: Of 771 respondents
      who met study criteria, 195 (25%) were responsive to DTC. Only 7% respondents
      taking no prescription were responsive, whereas 45% of respondents taking 5 or
      more prescription medications were responsive. This trend remained significant (p
      trend .0009) even when controlling for age, gender, race, educational attainment,
      income, self-reported health status, and whether respondents "liked" DTC
      advertising. There was no relationship between the number of OTC medications
      taken and the propensity to discuss health-related problems in response to DTC
      advertisements (p = .4). CONCLUSION: There is a strong cross-sectional
      relationship between the number of prescription, but not OTC, drugs used and
      responsiveness to DTC advertising. Although this relationship could be explained
      by physician compliance with patient requests for medications, it is also
      plausible that DTC advertisements have a particular appeal to patients prone to
      taking multiple medications. Outpatients motivated to discuss medical conditions
      based on their exposure to DTC advertising may require a careful medication
      history to evaluate for therapeutic duplication or overmedication.

PMID- 21942939
TI  - Quality of life after chemotherapy or hematopoietic cell transplant in follicular
      lymphoma: what's next?

PMID- 21942941
TI  - Colour, face, and visuospatial imagery abilities in low-vision individuals with
      visual field deficits.
AB  - This study investigates to what extent visual perception integrity is necessary
      for visual mental imagery. Sixteen low-vision participants with severe peripheral
      visual field loss, 16 with severe central field loss, 6 left brain-damaged
      patients with right homonymous hemianopia, 6 right brain-damaged patients with
      left homonymous hemianopia, and 16 normally sighted controls performed perceptual
      and imagery tasks using colours, faces, and spatial relationships. Results showed
      that (a) the perceptual and mental image>ry disorders vary according to the type
      of visual field loss, (b) hemianopics had no more difficulties imagining spatial
      stimuli in their contralesional hemispace than in their ipsilesional one, and (c)
      the only hemianopic participant to have perceptual and mental imagery impairments
      suffered from attentional deficits. Results suggest that (a) visual memory is not
      definitively established, but rather needs perceptual practice to be maintained,
      and (b) that visual mental imagery may involve some of the attentional
      exploratory mechanisms that are employed in visual behaviour.

PMID- 21942940
TI  - Effects of parathyroid hormone-related protein and macrophage inflammatory
      protein-1alpha in Jurkat T-cells on tumor formation in vivo and expression of
      apoptosis regulatory genes in vitro.
AB  - Parathyroid hormone-related protein (PTHrP) and macrophage inflammatory protein
      1alpha (MIP-1alpha) have been implicated in the pathogenesis of adult T-cell
      leukemia/lymphoma, but their effects on T-cells have not been well studied. Here
      we analyzed the functions of PTHrP and MIP-1alpha on T-cell growth and death both
      in vitro and in vivo by overexpressing either factor in human Jurkat T-cells.
      PTHrP or MIP-1alpha did not affect Jurkat cell growth in vitro, but PTHrP
      increased their sensitivity to apoptosis. Importantly, PTHrP and MIP-1alpha
      decreased both tumor incidence and growth in vivo. To investigate possible
      mechanisms, polymerase chain reaction (PCR) arrays and real-time reverse
      transcription (RT)-PCR assays were performed. Both PTHrP and MIP-1alpha increased
      the expression of several factors including signal transducer and activator of
      transcription 4, tumor necrosis factor alpha, receptor activator of nuclear
      factor kappaB ligand and death-associated protein kinase 1, and decreased the
      expression of inhibitor of DNA binding 1, interferon gamma and CD40 ligand in
      Jurkat cells. In addition, MIP-1alpha also increased the expression of
      transcription factor AP-2alpha and PTHrP increased expression of the vitamin D3
      receptor. These data demonstrate that PTHrP and MIP-1alpha exert a profound
      antitumor effect presumably by increasing the sensitivity to apoptotic signals
      through modulation of transcription and apoptosis factors in T-cells.

PMID- 21942951
TI  - A school-based resilience intervention to decrease tobacco, alcohol and marijuana
      use in high school students.
AB  - BACKGROUND: Despite schools theoretically being an ideal setting for accessing
      adolescents and preventing initiation of substance use, there is limited evidence
      of effective interventions in this setting. Resilience theory provides one
      approach to achieving such an outcome through improving adolescent mental well
      being and resilience. A study was undertaken to examine the potential
      effectiveness of such an intervention approach in improving adolescent resilience
      and protective factor scores; and reducing the prevalence of adolescent tobacco,
      alcohol and marijuana use in three high schools. METHODS: A non-controlled before
      and after study was undertaken. Data regarding student resilience and protective
      factors, and measures of tobacco, alcohol and marijuana use were collected from
      grade 7 to 10 students at baseline (n = 1449) and one year following a three year
      intervention (n = 1205). RESULTS: Significantly higher resilience and protective
      factors scores, and significantly lower prevalence of substance use were evident
      at follow up. CONCLUSIONS: The results suggest that the intervention has the
      potential to increase resilience and protective factors, and to decrease the use
      of tobacco, alcohol and marijuana by adolescents. Further more rigorous research
      is required to confirm this potential.

PMID- 21942952
TI  - [The role of coronary reserve in diagnosis of hemodynamically significant
      stenoses in anterior descending and right coronary arteries: transthoracic
      ultrasound study].
AB  - Analysis of possibilities of transthoracic echocardiography (TTEchoCG) diagnosis
      of hemodynamically significant stenoses of anterior descending and right coronary
      arteries (ADCA and RCA) based on Doppler assessment of coronary reserve (CR) was
      carried out in 73 patients with cardiac pain syndrome (mean age 48+/-7 years, 60
      men, 13 women). As a referent method we used coronary angiography. Coronary blood
      flow at baseline and during administration of a vasodilator (dipyridamole up to
      0.84 mg/kg) was assessed by broadband ultrasound transducer in the mode of
      noncontrast tissue second harmonic imaging in distal segments of ADCA and
      posterior interventricular artery (PIVA). CR was calculated as ratio of peak
      hyperemic to baseline diastolic coronary blood flow velocity. CR <2.0 was
      diagnosed as lowered. We found that TTEchoCG was simple noninvasive method of
      assessment of CR in distal thirds of ADCA and PIVA, which can be fulfilled in 90
      and 86%of patients, respectively. We also revealed that hemodynamically
      significant stenoses of ADCA and PIVA caused CR lowering distally to zone of
      stenosis and that degree of CR lowering depended on severity of vascular
      narrowing. We found that CR<2.0 in distal third of ADCA was a predictor of its
      >50% narrowing with sensitivity 78%, specificity 85%, positive predictive value
      (PPV) 67%, and negative predictive value (NPV) 90%. In the presence of >70% ADCA
      stenosis sensitivity and NPV of the parameter reached 100%. We revealed that
      CR<2.0 in PIVA served as a marker of >50% RCA stenosis with sensitivity 88%,
      specificity 86%, PPV 68%, and NPV 95%. In the presence of >70% RCA stenosis
      sensitivity and NPV of the parameter rose up to 92 and 97%, respectively.

PMID- 21942950
TI  - Evolutionary traces decode molecular mechanism behind fast pace of myosin XI.
AB  - BACKGROUND: Cytoplasmic class XI myosins are the fastest processive motors known.
      This class functions in high-velocity cytoplasmic streaming in various plant
      cells from algae to angiosperms. The velocities at which they process are ten
      times faster than its closest class V homologues. RESULTS: To provide sequence
      determinants and structural rationale for the molecular mechanism of this fast
      pace myosin, we have compared the sequences from myosin class V and XI through
      Evolutionary Trace (ET) analysis. The current study identifies class-specific
      residues of myosin XI spread over the actin binding site, ATP binding site and
      light chain binding neck region. Sequences for ET analysis were accumulated from
      six plant genomes, using literature based text search and sequence searches,
      followed by triple validation viz. CDD search, string-based searches and
      phylogenetic clustering. We have identified nine myosin XI genes in sorghum and
      seven in grape by sequence searches. Both the plants possess one gene product
      each belonging to myosin type VIII as well. During this process, we have re
      defined the gene boundaries for three sorghum myosin XI genes using fgenesh
      program. CONCLUSION: Molecular modelling and subsequent analysis of putative
      interactions involving these class-specific residues suggest a structural basis
      for the molecular mechanism behind high velocity of plant myosin XI. We propose a
      model of a more flexible switch I region that contributes to faster ADP release
      leading to high velocity movement of the algal myosin XI.

PMID- 21942953
TI  - [Heart failure and imbalance of chemical elements in myocardium of patients with
      ishemic heart disease].
AB  - Tissue content of chemical elements indirectly characterizes some metabolic
      processes. We have analyzed content of chemical elements in left and right
      ventricular myocardium of patients with ischemic heart disease with progressing
      heart failure and have shown that during development and progression of heart
      failure metabolic processes have unidirectional character in myocardium of both
      ventricles. Derangement of left ventricular contractile capacity is associated
      with lowering of content of microelements involved in antioxidant processes and
      energy metabolism in tissues (Cu, Mn, Cr) and elevated concentration of elements
      characterizing progressive of myocardial stiffness (Ca, Fe).

PMID- 21942954
TI  - [Prognostic value of diastolic dysfunction for sudden cardiac death of patients
      after myocardial  infarction].
AB  - We studied prognostic value of left ventricular (LV) diastolic dysfunction (DD)
      in relation to sudden cardiac death (SCD) after myocardial infarction (MI). We
      examined 603 patients in acute period of MI (including 551 with preserved LV
      systolic function and DD). Duration of follow-up was 1-7 years. According to data
      of Cox multifactorial regression analysis LVDD was not an independent prognostic
      factor. ut it increased SCD risk at the account of interrelationship with such
      predictors as ventricular rhythm disturbances, lowering of heart rate
      variability, and sensitivity of cardiochronotropic component of arterial
      baroreflex.

PMID- 21942955
TI  - [Possibilities of a preparation omega-3 polyunsaturated fatty acids in the
      treatment of patients with ventricular arrhythmias and myocardial infarction].
AB  - The aim was to study the effectiveness of prescription medication containing 90%
      omega-3 polyunsaturated fatty acids for 6 months on ventricular arrhythmias in
      patients with myocardial infarction less than a year ago. The study involved 56
      patients with ventricular extrasystoles, from 500 to 1000 per day. Divided into
      two groups of patients we divided into I group - 30 people - received in addition
      to standard drug therapy of omega-3 PUFA 1 g daily, for 6 months; II group - 26
      men were given only previously assigned therapies. The average age of patients in
      group I - 60,7+/-8,6, II group - 61+/-9,7 years (p> 0,05). ECG monitoring was
      performed at 3 and 6 months. Administration of highly concentration preparation
      of omega-3 PUFAs for 3 months reduced number of PVCs per day, frequencies of
      grades 2, 3, 4A, 4B, and high grade PVCs (grades 3 - 5) as a whole. These effects
      persisted after 6 months of treatment.

PMID- 21942956
TI  - [Predictive value C-reactive protein assessment level in women with arterial
      hypertension].
AB  - Classic modifiable cardiovascular risk factors, such as blood pressure and
      dyslipidaemia are incorporated into clinical practice to estimate the 10-year
      risk of fatal cardiovascular disease (CVD): the SCORE project. To improve CVD
      risk estimation in women we compared predictive value of two models: risk chart
      based on the SCORE study and the Reynolds Risk Score in 134 women with
      hypertension to optimise risk stratification and preventive strategies in high
      risk individuals. We concluded that Reynolds Risk model causes clinically
      relevant changes in risk category classification compared to risk chart SCORE and
      improves risk stratification. Addition of C-reactive protein to Reynolds Risk
      model improves it predictive value regardless of other risk factors. C-reactive
      protein is a strong marker of atherosclerosis, can be useful in women for risk
      stratification in daily practice regardless of risk prediction model.

PMID- 21942957
TI  - [Alternative therapy with ivabradine in patients with functional class III
      chronic heart failure].
AB  - Aim of the study - to determine efficacy of therapy with the use of ivabradine in
      patients with functional class (FC) III chronic heart failure (CHF) on the basis
      of assessment of its action on regulatory adaptive status (RAS). We included into
      the study 100 patients with FC III CHF at the background of ischemic heart
      disease (IHD) and/or stage III hypertensive disease (HD) receiving complex
      therapy (quinapril, torasemide, spironolactone). After randomization group 1
      comprised 56 patients (age 62.9+/-1.8 years) who were prescribed slow release
      metoprolol succinate (59.1+/-4.5 mg/day). Group 2 comprised 44 patients (age
      59.4+/-1.3 years) who were prescribed If channel inhibitor ivabradine (12.1+/-2.3
      mg/day) if beta-blocker use was not possible. Examination at baseline and in 6
      months included treadmillometry with assessment of maximal oxygen consumption
      (VO2 max) at exercise, echocardiography, 24-hour blood pressure monitoring,
      measurement of N-terminal pro-brain natriuretic peptide (NT-proBNP) in blood
      plasma. For objective qualitative assessment of the state of RAS we used a test
      of cardio-respiratory synchronism. Therapy with the use of ivabradine improved
      structural and functional state of the myocardium, elevated tolerance to
      exercise, caused positive changes of NT-proBNP concentration in blood plasma and
      VO2 max at exercise. Thus ivabradine probably can serve as alternative to 
      adrenoblockers when their use is not possible patients with FC III CHF at the
      background of IHD and/or stage III HD.

PMID- 21942958
TI  - [Special characteristics of chronotropic reaction to physical exercise in
      patients with systolic heart failure and obstructive sleep apnea syndrome].
AB  - In order to study special characteristics of chronotropic reaction to physical
      exercise on veloergometer in the presence of obstructive sleep apnea (OSA) we
      examined 84 patients with manifestations of chronic systolic heart failure (HF).
      Chronotropic insufficiency was found in 88% of patients predominantly in
      combination with insufficient lowering of heart rate after exercise. At the same
      time it was more rarely registered in patients with OSA (56.4%). Insufficient
      lowering of heart rate by the end of first minute of rest was similarly
      associated with HF and OSA. CONCLUSION: it is necessary to consider
      simultaneously chronotropic reserve and character of HR recovery after exercise.

PMID- 21942959
TI  - [Clinical value of insulin resistance in fasting  normoglycemia].
AB  - Aim of the study was to clarify the question of the presence of manifestations of
      insulin resistance (IR) in fasting normoglycemia and to assess their association
      with risk of development and presence of clinically overt cardiovascular diseases
      (CVD) caused by atherosclerosis. We included into this study 1127 men and women
      older than 55 years with normal blood serum level of glucose in fasting state
      (<6.1 mmol/l) without diabetes mellitus selected from a random sample of Moscow
      inhabitants (n=1186). In participants selected for this study we determined risk
      factors, calculated indexes of IR (HOMA-IR) and functional capacity of pancreatic
      -cells (HOMA-%B) using fasting levels of glucose and insulin. The examined
      subsample was divided into quartiles according to values of HOMA-IR. It was shown
      that in the 4-th quartile HOMA-%B was substantially higher than in other
      quartiles. With this values of body mass index and waist circumference were also
      highest in the 4-th quartile. Fasting insulin level compared with glucose level
      contributed more to determination of values of indexes of both IR and functional
      capacity of pancreatic -cells. In the upper 4-th quartile signs of atherogenic
      dyslipidemia appearing as higher concentration of triglycerides and lowered
      concentration of high density lipoprotein cholesterol manifested to the greatest
      degree. At statistical analysis of probability of CVD with clinical
      manifestations it was shown that in the 4-th quartile of distribution of HOMA-IR
      (>2.7) values of odds ratio (OR) of development of arterial hypertension (AH),
      total CVD, angina pectoris, history of brain stroke were elevated. With that in
      the 3-rd quartile of distribution i.e. at HOMA-IR >1.9 there were higher ORs of
      development of AH, CVD, angina pectoris. Thus even in the range of normal fasting
      glucose concentrations in subjects older than 55 years we detected IR associated
      with elevated risk of development of atherosclerosis related CVD. For detection
      of IR it is appropriate to measure in blood serum not only concentration of
      glucose but also fasting insulin level with subsequent calculation of HOMA-IR and
      HOMA-%B indexes.

PMID- 21942960
TI  - [Polymorphisms of alpha-2-beta-adrenergic receptor and endothelial NO-synthase
      genes in patients with atrial fibrillation].

PMID- 21942961
TI  - [Noninvasive diagnosis of acute cellular rejection of transplanted heart].
AB  - Endomyocardial biopsy remains the gold standard of diagnosis of acute cellular
      rejection after heart transplantation. However, routine biopsies are of major
      inconvenience to patients and are also risky and costly. In the present research
      we considered possibility of non-invasive diagnosis of acute cellular rejection
      in patients after orthotopic heart transplantation. Results of research are based
      on studying 34 endomyocardial biopsys in combination with Holter monitoring and
      ECHO findings in 21 heart recipients. It is demonstrated that case follow-up with
      Holter monitoring and ECHO is mandatory for diagnosis of acute cellular rejection
      and optimal treatment tactics.

PMID- 21942962
TI  - [Prevalence and clinical significance of multifocal  atherosclerosis in patients
      with ischemic heart  disease].
AB  - This review is devoted to the problem of detection of multifocal atherosclerosis
      (MFA) in patients with acute and chronic forms of ischemic heart disease (IHD).
      According to different sources rate of detection of MFA varies between 13.5 and
      94%. According to register study conducted in the Kemerovo cardiological center
      it has been proved that isolated involvement of coronary vascular bed is an
      exemption and that some degree of MFA is found in most patients with ST-elevation
      myocardial infarction. It is considered that estimating thickness of carotid
      artery intima-media complex, degree of stenosis of extracoronary arteries one can
      not only predict severity of coronary atherosclerosis but also assess total risk
      of development of vascular catastrophes. According to results of our studies it
      has been shown that in patients with ST-elevation myocardial infarction and even
      hemodynamically insignificant stenoses in extracoronary vascular beds 12 month
      prognosis is substantially worse than in patients with MI without signs of MFA.
      In this connection it is necessary to include into routine practice of physicians
      observing patients with pathology of any vascular bed active detection and
      monitoring of involvement of other vascular beds in order to make timely decision
      on the use of effective methods of treatment and prevention of ischemic events.

PMID- 21942963
TI  - [Lengres disease].

PMID- 21942964
TI  - [Application of AT1-angiotensin II receptor blocker valsartan in clinical
      practice].

PMID- 21942965
TI  - [Diagnosis and options for reconstructive heart valve surgery in the Marfan
      syndrome].
AB  - Marfan syndrome is a disorder of the connective tissue that is inherited in an
      autosomal-dominant fashion and that is caused by mutations in the gene coding for
      fibrillin-1, FBN1. Although complications of the syndrome may involve the eye,
      the lung and the skeleton, the high mortality of untreated cases results almost
      exclusively from cardiovascular complications, including aortic dissection,
      rupture and mitral valve regurgitation. The multiorgan involvement of many of
      these syndromes requires multidisciplinary expert centers that can increase the
      average life expectancy of affected patients from only 32 years to over 60 years.
      The present article both reviews classical standards of managing cardiovascular
      manifestations and highlights the surgical approach for aortic and mitral valve
      surgery in Marfan patients.

PMID- 21942966
TI  - [Diagnosis and effective surgical treatment of constrictive pericarditis].
AB  - Constrictive pericarditis is a rare and severe disease. Timely and correct
      differential diagnosis of this pathology facilitates choice of necessary tactics
      of treatment and thus improve prognosis and quality of life. In this paper we
      present clinical case report of a patient with constrictive pericarditis. The
      disease was diagnosed on the basis of clinical picture, data of X-ray and
      echocardiographic investigation, and confirmed by multispiral computed tomography
      (MSCT). The patient was subjected to pericardioectomy with positive clinical
      effect and results of repeated echocardiography and MSCT.

PMID- 21942967
TI  - Monitoring air pollution: use of early warning systems for public health.
AB  - Research confirming the detrimental impact poor ambient air quality and episodes
      of abnormally high pollutants has on public health, plus differential
      susceptibility, calls for improved understanding of this complex topic among all
      walks of society. The public and particularly, vulnerable groups, should be aware
      of their quality of air, enabling action to be taken in the event of increased
      pollution. Policy makers must have a sound awareness of current air quality and
      future trends, to identify issues, guide policies and monitor their
      effectiveness. These attitudes are dependent upon air pollution monitoring,
      forecasting and reporting, serving all interested parties. Apart from the
      underlying national regulatory obligation a country has in reporting air quality
      information, data output serves several purposes. This review focuses on
      provision of real-time data and advanced warnings of potentially health-damaging
      events, in the form of national air quality indices and proactive alert services.
      Some of the challenges associated with designing these systems include technical
      issues associated with the complexity of air pollution and its science. These
      include inability to provide precise exposure concentrations or guidance on long
      term/cumulative exposures or effects from pollutant combinations. Other issues
      relate to the degree to which people are aware and positively respond to these
      services. Looking to the future, mobile devices such as cellular phones, equipped
      with sensing applications have potential to provide dynamic, temporally and
      spatially precise exposure measures for the mass population. The ultimate aim
      should be to empower people to modify behaviour-for example, when to increase
      medication, the route/mode of transport taken to school or work or the
      appropriate time to pursue outdoor activities-in a way that protects their health
      as well as the quality of the air they breathe.

PMID- 21942968
TI  - Forskolin enhances in vivo bone formation by human mesenchymal stromal cells.
AB  - Activation of the protein kinase A (PKA) pathway with dibutyryl cyclic adenosine
      monophosphate (db-cAMP) was recently shown to enhance osteogenic differentiation
      of human mesenchymal stromal cells (hMSCs) in vitro and bone formation in vivo.
      The major drawback of this compound is its inhibitory effect on proliferation of
      hMSCs. Therefore, we investigated whether fine-tuning of the dose and timing of
      PKA activation could enhance bone formation even further, with minimum effects on
      proliferation. To test this, we selected two different PKA activators (8-bromo
      cAMP (8-br-cAMP) and forskolin) and compared their effects on proliferation and
      osteogenic differentiation with those of db-cAMP. We found that all three
      compounds induced alkaline phosphatase levels, bone-specific target genes, and
      secretion of insulin-like growth factor-1, although 8-br-cAMP induced adipogenic
      differentiation in long-term cultures and was thus considered unsuitable for
      further in vivo testing. All three compounds inhibited proliferation of hMSCs in
      a dose-dependent manner, with forskolin inhibiting proliferation most. The effect
      of forskolin on in vivo bone formation was tested by pretreating hMSCs before
      implantation, and we observed greater amounts of bone using forskolin than db
      cAMP. Our data show forskolin to be a novel agent that can be used to increase
      bone formation and also suggests a role for PKA in the delicate balance between
      adipogenic and osteogenic differentiation.

PMID- 21942970
TI  - Pharmacokinetics of Cyclosporine A in Chinese heart transplant recipients.
AB  - AIM: To determine the steady state concentration and the pharmacokinetics of
      Cyclosporine A (CsA) in heart transplant recipients. METHODS: A single dose of
      100 mg CsA capsules twice daily was given to five heart transplant recipients of
      steady state. The concentrations of CsA in plasma were determined by streptavidin
      peroxidase fluorescent polarization immunoassay. RESULTS: The main
      pharmacokinetic parameters of CsA were as follows: t(max) (1.60 +/- 0.55) h,
      rhomax(951.60 +/- 229.20) MUg.L-1, t1/2(6.53 +/- 2.40) h, and AUC0 -t(5162.10 +/-
      1355.01) MUg.h.L-1. CONCLUSION: The study obtained the steady state
      pharmacokinetic parameters of CsA in Chinese heart transplant recipients.

PMID- 21942969
TI  - Complications after radical gastrectomy following FOLFOX7 neoadjuvant
      chemotherapy for gastric cancer.
AB  - BACKGROUND: This study assessed the postoperative morbidity and mortality
      occurring in the first 30 days after radical gastrectomy by comparing gastric
      cancer patients who did or did not receive the FOLFOX7 regimen of neoadjuvant
      chemotherapy. METHODS: We completed a retrospective analysis of 377 patients
      after their radical gastrectomies were performed in our department between 2005
      and 2009. Two groups of patients were studied: the SURG group received surgical
      treatment immediately after diagnosis; the NACT underwent surgery after 2-6
      cycles of neoadjuvant chemotherapy. RESULTS: There were 267 patients in the SURG
      group and 110 patients in the NACT group. The NACT group had more proximal
      tumours (P = 0.000), more total/proximal gastrectomies (P = 0.000) and longer
      operative time (P = 0.005) than the SURG group. Morbidity was 10.0% in the NACT
      patients and 17.2% in the SURG patients (P = 0.075). There were two cases of
      postoperative death, both in the SURG group (P = 1.000). No changes in
      complications or mortality rate were observed between the SURG and NACT groups.
      CONCLUSION: The FOLFOX7 neoadjuvant chemotherapy is not associated with increased
      postoperative morbidity, indicating that the FOLFOX7 neoadjuvant chemotherapy is
      a safe choice for the treatment of local advanced gastric cancer.

PMID- 21942971
TI  - Mathematical multi-scale model of the cardiovascular system including mitral
      valve dynamics. Application to ischemic mitral insufficiency.
AB  - BACKGROUND: Valve dysfunction is a common cardiovascular pathology. Despite
      significant clinical research, there is little formal study of how valve
      dysfunction affects overall circulatory dynamics. Validated models would offer
      the ability to better understand these dynamics and thus optimize diagnosis, as
      well as surgical and other interventions. METHODS: A cardiovascular and
      circulatory system (CVS) model has already been validated in silico, and in
      several animal model studies. It accounts for valve dynamics using Heaviside
      functions to simulate a physiologically accurate "open on pressure, close on
      flow" law. However, it does not consider real-time valve opening dynamics and
      therefore does not fully capture valve dysfunction, particularly where the
      dysfunction involves partial closure. This research describes an updated version
      of this previous closed-loop CVS model that includes the progressive opening of
      the mitral valve, and is defined over the full cardiac cycle. RESULTS:
      Simulations of the cardiovascular system with healthy mitral valve are performed,
      and, the global hemodynamic behaviour is studied compared with previously
      validated results. The error between resulting pressure-volume (PV) loops of
      already validated CVS model and the new CVS model that includes the progressive
      opening of the mitral valve is assessed and remains within typical measurement
      error and variability. Simulations of ischemic mitral insufficiency are also
      performed. Pressure-Volume loops, transmitral flow evolution and mitral valve
      aperture area evolution follow reported measurements in shape, amplitude and
      trends. CONCLUSIONS: The resulting cardiovascular system model including mitral
      valve dynamics provides a foundation for clinical validation and the study of
      valvular dysfunction in vivo. The overall models and results could readily be
      generalised to other cardiac valves.

PMID- 21942972
TI  - Management of antiplatelet therapy inpatients at risk for coronary
      StentThrombosis undergoing non-cardiac surgery.
AB  - Percutaneous coronary interventions (PCIs) have become the most commonly
      performed coronary revascularization procedures. At the same time, there is an
      increased likelihood that patients with intracoronary stents will need to undergo
      surgery. Two serious consequences emerge from this situation: (i) stent
      thrombosis in relation to discontinuation of antiplatelet therapy, and (ii) major
      bleeding in relation to continuation of antiplatelet therapy. The best solution
      to overcome the risks resulting from surgery performed in patients after stent
      implantation is to postpone the operation until after re-endothelialization of
      the vessel surface is completed. Expert recommendations advise that patients can
      be sent for non-cardiac surgery 3 months after bare-metal stent PCI and 12 months
      after drug-eluting stent PCI, with continuation of aspirin therapy. Difficult
      decisions regarding antiplatelet management arise when a patient that is still
      receiving dual antiplatelet therapy with aspirin and a thienopyridine has to
      undergo surgery that cannot be postponed. Discussions between the treating
      cardiologist, the surgeon and the anaesthesiologist about this situation are
      recommended in order to achieve a reasonable expert consensus.

PMID- 21942973
TI  - Neuraxial morphine and respiratory depression: finding the right balance.
AB  - Morphine is a drug commonly administered via the epidural or intrathecal route,
      and is regarded by many as the 'gold-standard' single-dose neuraxial opioid due
      to its postoperative analgesic efficacy and prolonged duration of action.
      However, respiratory depression is a recognized side effect of neuraxial morphine
      administered in the perioperative setting. We conducted an extensive review of
      articles published since 1945 that examine respiratory depression or failure
      associated with perioperative intrathecal or epidural morphine use. Respiratory
      depression was previously thought to result from the interaction of opioid in the
      cerebrospinal fluid with ventral medullary opioid receptors. More recently, the
      preBotzinger complex located in the medulla has been identified as the site
      responsible for the decrease in respiratory rate following systemic
      administration of opioids. Neurons in the preBotzinger complex expressing
      neurokinin-1 receptors are selectively inhibited by opioids, and therefore are
      the mediators of opioid-induced respiratory depression. Epidural, intrathecal and
      plasma pharmacokinetics of opioids are complex, vary between neuraxial
      compartments, and can even differ within the epidural space itself depending upon
      level of insertion. Caution should be exercised when prescribing systemic opioids
      (intravenous or oral) in addition to neuraxial morphine as this can compound the
      potential for early or delayed respiratory depression. There is a wide range of
      incidences for respiratory depression following neuraxial morphine in a
      perioperative setting. Disparity of definitions used for the diagnosis of
      respiratory depression in the literature precludes identification of the exact
      incidence of this rare event. The optimal neuraxial opioid dose is a balance
      between the conflicting demands of providing optimal analgesia while minimizing
      dose-related adverse effects. Dose-response studies show that neuraxial morphine
      appears to have an analgesic efficacy 'ceiling'. The optimal 'single-shot'
      intrathecal dose appears to be 0.075-0.15 mg and the ideal 'single-shot' epidural
      morphine dose is 2.5-3.75 mg. Analgesic efficacy studies have not been adequately
      powered to show differences in the incidence of clinically significant
      respiratory depression. Opioid antagonists such as naloxone to prevent or treat
      opioid-induced respiratory depression have a number of limitations. Researchers
      have recently focused on non-opioid drugs such as serotonin receptor agonists.
      Early evidence suggests that ampakine (alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionic acid [AMPA]) receptor modulators may be effective at reducing opioid
      induced respiratory depression while maintaining analgesia. Sodium/proton
      exchanger type 3 (NHE3) inhibitors, which act centrally on respiratory pathways,
      also warrant further study.

PMID- 21942975
TI  - Biomarkers of therapeutic response in patients with chronic obstructive pulmonary
      disease: a critical review of the literature.
AB  - Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and
      mortality across the world. Unfortunately, none of the current therapies, except
      for smoking cessation and supplemental domiciliary oxygen for hypoxaemic
      patients, can modify its natural course or alter survival. The pipeline for new
      compounds is not very promising owing to repeated failures, and many large
      pharmaceutical companies have abandoned COPD drug discovery altogether. One major
      barrier to new drug discovery is the lack of modifiable biomarkers that can be
      used as surrogates of clinical outcomes such as exacerbation and mortality. The
      only accepted marker in COPD is forced expiratory volume in 1 second (FEV(1)).
      However, by definition, COPD is a non-reversible or poorly reversible condition
      with respect to FEV(1). Thus, very few drugs except for bronchodilators have been
      able to address this endpoint. Of many candidate molecules, sputum neutrophil
      counts, exhaled corrected alveolar nitric oxide and proline-glycine-proline (PGP)
      and N-alpha-PGP, which are breakdown products of collagen, are promising lung
      based biomarkers. However, their clinical utility has not been validated in large
      clinical trials. Promising blood biomarkers include surfactant protein D, and
      pulmonary- and activation-regulated chemokine (PARC/CCL-18). However, the
      clinical data have been inconsistent. Non-specific inflammatory biomarkers such
      as C-reactive protein and interleukin-6 lack specificity for COPD and thus are of
      limited clinical usefulness.

PMID- 21942977
TI  - Subcutaneous recombinant interferon-beta-1a (Rebif(r)): a review of its use in
      the treatment of relapsing multiple sclerosis.
AB  - Subcutaneous recombinant interferon-beta-1a (SC IFNbeta-1a) [Rebif(r)] is
      indicated as monotherapy for the prevention of relapses and progression of
      physical disability in patients with relapsing multiple sclerosis (MS). This
      article reviews the efficacy and tolerability of SC IFNbeta-1a in this
      indication, with further discussion of its pharmacological properties and
      pertinent pharmacoeconomic studies. SC IFNbeta-1a efficacy and tolerability were
      evaluated in randomized, double-blind, multinational trials in patients with
      relapsing-remitting MS (RRMS). Its efficacy was demonstrated in the 2-year PRISMS
      trial, as SC IFNbeta-1a 22 or 44 MUg three times weekly (tiw) significantly
      reduced relapse rates, with an ~30% relative risk reduction compared with
      placebo. SC IFNbeta-1a was also associated with significantly delayed progression
      of disability, and lower disease activity according to MRI, relative to placebo.
      In the 24-week EVIDENCE trial, a significantly higher proportion of SC IFNbeta-1a
      44 MUg tiw than intramuscular IFNbeta-1a (Avonex(r)) 30 MUg once weekly
      recipients remained relapse free. A serum-free formulation of SC IFNbeta-1a 44
      MUg tiw was more efficacious than placebo in preventing the development of brain
      lesions in the 16-week IMPROVE trial. In the 96-week REGARD trial, the efficacy
      of SC IFNbeta-1a 44 MUg tiw was not significantly different to that of glatiramer
      acetate for clinical endpoints, although it was associated with reduced
      development of brain lesions compared with glatiramer acetate, according to some
      MRI endpoints. In the 36-month CAMMS223 trial, alemtuzumab led to significantly
      lower relapse rates and risk of developing sustained disability than SC IFNbeta
      1a 44 MUg tiw, and was generally more efficacious according to other clinical and
      MRI endpoints. Across trials, influenza-like symptoms, injection-site reactions,
      haematological disturbances and hepatic enzyme abnormalities were the most common
      treatment-emergent adverse events occurring with SC IFNbeta-1a. In the PRISMS
      trial, SC IFNbeta-1a 22 and 44 MUg tiw recipients had more injection-site
      reactions than placebo recipients and, at the higher dosage, haematological
      disturbances and increases in ALT levels were also significantly more frequent
      than with placebo. Pooled data from clinical trials and postmarketing
      surveillance indicate that haematological and hepatic adverse events are
      generally asymptomatic and rarely result in treatment discontinuation.
      Nevertheless, some cases of serious hepatic complications have been reported. In
      cost-utility studies, first-line therapies for RRMS, including SC IFNbeta-1a, all
      exceeded commonly accepted US thresholds for incremental cost per quality
      adjusted life-years gained relative to symptomatic treatment. However, because of
      patient need and the difficulty in adequately assessing cost utility in a
      gradually progressive disease, these agents have been made available to many
      patients worldwide through special access programmes. Overall, SC IFNbeta-1a has
      a favourable risk-benefit ratio and is a valuable first-line treatment option for
      patients with relapsing MS.

PMID- 21942976
TI  - Clinically significant drug interactions with antacids: an update.
AB  - One may consider that drug-drug interactions (DDIs) associated with antacids is
      an obsolete topic because they are prescribed less frequently by medical
      professionals due to the advent of drugs that more effectively suppress gastric
      acidity (i.e. histamine H(2)-receptor antagonists [H2RAs] and proton pump
      inhibitors [PPIs]). Nevertheless, the use of antacids by ambulant patients may be
      ever increasing, because they are freely available as over-the-counter (OTC)
      drugs. Antacids consisting of weak basic substances coupled with polyvalent
      cations may alter the rate and/or the extent of absorption of concomitantly
      administered drugs via different mechanisms. Polyvalent cations in antacid
      formulations may form insoluble chelate complexes with drugs and substantially
      reduce their bioavailability. Clinical studies demonstrated that two classes of
      antibacterials (tetracyclines and fluoroquinolones) are susceptible to clinically
      relevant DDIs with antacids through this mechanism. Countermeasures against this
      type of DDI include spacing out the dosing interval - taking antacid either 4
      hours before or 2 hours after administration of these antibacterials.
      Bisphosphonates may be susceptible to DDIs with antacids by the same mechanism,
      as described in the prescription information of most bisphosphonates, but no
      quantitative data about the DDIs are available. For drugs with solubility
      critically dependent on pH, neutralization of gastric fluid by antacids may alter
      the dissolution of these drugs and the rate and/or extent of their absorption.
      However, the magnitude of DDIs elicited by antacids through this mechanism is
      less than that produced by H2RAs or PPIs; therefore, the clinical relevance of
      such DDIs is often obscure. Magnesium ions contained in some antacid formulas may
      increase gastric emptying, thereby accelerating the rate of absorption of some
      drugs. However, the clinical relevance of this is unclear in most cases because
      the difference in plasma drug concentration observed after dosing shortly
      disappears. Recent reports have indicated that some of the molecular-targeting
      agents such as the tyrosine kinase inhibitors dasatinib and imatinib, and the
      thrombopoietin receptor agonist eltrombopag may be susceptible to DDIs with
      antacids. Finally, the recent trend of developing OTC drugs as combination
      formulations of an antacid and an H2RA is a concern because these drugs will
      increase the risk of DDIs by dual mechanisms, i.e. a gastric pH-dependent
      mechanism by H2RAs and a cation-mediated chelation mechanism by antacids.

PMID- 21942978
TI  - Fibrin sealant (evicel(r) [quixil(r)/crossealTM]): a review of its use as
      supportive treatment for haemostasis in surgery.
AB  - Evicel(r) is a fibrin sealant consisting of two components, human clottable
      protein (predominantly human fibrinogen) and human thrombin. It is indicated as
      supportive treatment in patients undergoing surgery when control of bleeding by
      standard surgical techniques is ineffective or impractical. Evicel(r) is a new
      formulation of the previously available fibrin sealant Quixil(r) (in the EU) or
      CrossealTM (in the US). Evicel(r) differs from Quixil(r)/CrossealTM in that its
      fibrinogen component does not contain the antifibrinolytic agent tranexamic acid,
      which is potentially neurotoxic, resulting in Quixil(r)/CrossealTM being
      contraindicated for use in neurosurgery. The removal of tranexamic acid did not
      affect the haemostatic efficacy or longevity of Evicel(r) fibrin clots and
      allowed the sealant to be granted an expanded indication. Evicel(r) and
      Quixil(r)/CrossealTM are easy to use and, since they do not contain synthetic or
      bovine aprotinin, have a reduced potential for hypersensitivity reactions. This
      article reviews the pharmacological properties, clinical efficacy and
      tolerability of Evicel(r) and its previous formulation as supportive treatment
      for haemostasis in surgery. In clinical studies, Evicel(r) and
      Quixil(r)/CrossealTM were generally well tolerated and effective haemostatic
      agents for adjunctive use in various types of surgeries when conventional methods
      were impractical or ineffective in controlling bleeding. Two pivotal, randomized
      studies showed that Evicel(r) was significantly more effective than manual
      compression in patients undergoing vascular surgery, and significantly more
      effective than Surgicel(r) in patients undergoing retroperitoneal or intra
      abdominal surgery, as assessed by the proportion of patients achieving
      haemostasis. In another similarly designed pivotal study in patients undergoing
      liver resection, CrossealTM was significantly more effective than standard
      haemostatic agents (e.g. Surgicel(r)), as assessed by the mean time to
      haemostasis. The incidences of treatment-emergent adverse events in these studies
      were generally similar between the Evicel(r) or CrossealTM groups and the
      comparator groups. Quixil(r) was also generally well tolerated and an effective
      haemostatic agent in endonasal surgeries, and tonsillectomies and/or
      adenoidectomies, with some benefit of treatment with Evicel(r) or Quixil(r) also
      observed in orthopaedic surgeries. Although additional comparative studies with
      other haemostatic agents would help to definitively position Evicel(r) with
      respect to these agents, current evidence suggests that Evicel(r) is useful in
      surgeries for improving haemostasis where standard surgical techniques are
      insufficient.

PMID- 21942980
TI  - Strain-dependent variation in the early transcriptional response to CNS injury
      using a cortical explant system.
AB  - BACKGROUND: While it is clear that inbred strains of mice have variations in
      immunological responsiveness, the influence of genetic background following
      tissue damage in the central nervous system is not fully understood. A cortical
      explant system was employed as a model for injury to determine whether the
      immediate transcriptional response to tissue resection revealed differences among
      three mouse strains. METHODS: Immunological mRNAs were measured in cerebral
      cortex from SJL/J, C57BL/6J, and BALB/cJ mice using real time RT-PCR. Freshly
      isolated cortical tissue and cortical sections incubated in explant medium were
      examined. Levels of mRNA, normalized to beta-actin, were compared using one way
      analysis of variance with pooled samples from each mouse strain. RESULTS: In
      freshly isolated cerebral cortex, transcript levels of many pro-inflammatory
      mediators were not significantly different among the strains or too low for
      comparison. Constitutive, baseline amounts of CD74 and antisecretory factor (ASF)
      mRNAs, however, were higher in SJL/J and C57BL/6J, respectively. When sections of
      cortical tissue were incubated in explant medium, increased message for a number
      of pro-inflammatory cytokines and chemokines occurred within five hours. Message
      for chemokines, IL-1alpha, and COX-2 transcripts were higher in C57BL/6J cortical
      explants relative to SJL/J and BALB/cJ. IL-1beta, IL-12/23 p40, and TNF-alpha
      were lower in BALB/cJ explants relative to SJL/J and C57BL/6J. Similar to
      observations in freshly isolated cortex, CD74 mRNA remained higher in SJL/J
      explants. The ASF mRNA in SJL/J explants, however, was now lower than levels in
      both C57BL/6J and BALB/cJ explants. CONCLUSIONS: The short-term cortical explant
      model employed in this study provides a basic approach to evaluate an early
      transcriptional response to neurological damage, and can identify expression
      differences in genes that are influenced by genetic background.

PMID- 21942979
TI  - Fenofibrate: a review of its use in dyslipidaemia.
AB  - Fenofibrate is a fibric acid derivative indicated for the treatment of severe
      hypertriglyceridaemia and mixed dyslipidaemia in patients who have not responded
      to nonpharmacological therapies. The lipid-modifying effects of fenofibrate are
      mediated by the activation of peroxisome proliferator-activated receptor-alpha.
      Fenofibrate also has nonlipid, pleiotropic effects (e.g. reducing levels of
      fibrinogen, C-reactive protein and various pro-inflammatory markers, and
      improving flow-mediated dilatation) that may contribute to its clinical efficacy,
      particularly in terms of improving microvascular outcomes. Fenofibrate improves
      the lipid profile (particularly triglyceride [TG] and high-density lipoprotein
      cholesterol [HDL-C] levels) in patients with dyslipidaemia. Compared with statin
      monotherapy, fenofibrate monotherapy tends to improve TG and HDL-C levels to a
      significantly greater extent, whereas statins improve low-density lipoprotein
      cholesterol (LDL-C) and total cholesterol levels to a significantly greater
      extent. Fenofibrate is also associated with promoting a shift from small, dense,
      atherogenic LDL particles to larger, less dense LDL particles. Combination
      therapy with a statin plus fenofibrate generally improves the lipid profile to a
      greater extent than monotherapy with either agent in patients with dyslipidaemia
      and/or type 2 diabetes mellitus or the metabolic syndrome. In the pivotal FIELD
      and ACCORD trials in patients with type 2 diabetes, fenofibrate did not
      significantly reduce the risk of coronary heart disease events to a greater
      extent than placebo, and simvastatin plus fenofibrate did not significantly
      reduce the risk of major cardiovascular (CV) events to a greater extent than
      simvastatin plus placebo. However, the risk of some nonfatal macrovascular events
      and the incidence of certain microvascular outcomes were reduced significantly
      more with fenofibrate than with placebo in the FIELD trial, and in the ACCORD
      trial, patients receiving simvastatin plus fenofibrate were less likely to
      experience progression of diabetic retinopathy than those receiving simvastatin
      plus placebo. Subgroup analyses in the FIELD and ACCORD Lipid trials indicate
      that fenofibrate is of the greatest benefit in decreasing CV events in patients
      with atherogenic dyslipidaemia. Fenofibrate is generally well tolerated when
      administered alone or in combination with a statin. Thus, in patients with
      dyslipidaemia, particularly atherogenic dyslipidaemia, fenofibrate is a useful
      treatment option either alone or in combination with a statin.

PMID- 21942983
TI  - Disconnection hyperprolactinaemia in nonadenomatous sellar/parasellar lesions
      practically never exceeds 2000 mU/l.

PMID- 21942981
TI  - Disease control and functional outcome in three modern combined organ preserving
      regimens for locally advanced squamous cell carcinoma of the head and neck
      (SCCHN).
AB  - PURPOSE: To report our experience on disease control and functional outcome using
      three modern combined-modality approaches for definitive radiochemotherapy of
      locally advanced SCCHN with modern radiotherapy techniques: radiochemotherapy
      (RChT), radioimmunotherapy (RIT) with cetuximab, or induction chemotherapy with
      docetaxel, cisplatin, and 5-FU (TPF) combined with either RChT or RIT. METHODS:
      Toxicity and outcome was retrospectively analysed in patients receiving
      definitive RChT, RIT, or induction chemotherapy followed by RChT or RIT between
      2006 and 2009. Outcome was estimated using Kaplan-Meier analyses, toxicity was
      analysed according to CTCAE v 3.0. RESULTS: Thirty-eight patients were treated
      with RChT, 38 patients with RIT, 16 patients received TPF followed by either RChT
      or RIT. Radiotherapy was mostly applied as IMRT (68%). Long-term toxicity was
      low, only one case of grad III dysphagia requiring oesophageal dilatation, no
      case of either xerostomia >= grade II or cervical plexopathy were observed.
      Median overall survival (OS) was 25.7 months (RChT) and 27.7 months (RIT), median
      locoregional progression-free survival (PFS) was not reached yet. Subgroup
      analysis showed no significant differences between TPF, RChT, and RIT despite
      higher age and co-morbidities in the RIT group. Results suggested improved OS,
      distant and overall PFS for the TPF regimen. CONCLUSION: Late radiation effects
      in our cohort are rare. No significant differences in outcome between RChT and
      RIT were observed. Adding TPF suggests improved progression-free and overall
      survival, impact of TPF on locoregional PFS was marginal, therefore
      radiotherapeutic options for intensification of local treatment should be
      explored.

PMID- 21942982
TI  - Altered tryptophan and alanine transport in fibroblasts from boys with attention
      deficit/hyperactivity disorder (ADHD): an in vitro study.
AB  - BACKGROUND: The catecholaminergic and serotonergic neurotransmitter systems are
      implicated in the pathophysiology of attention-deficit/hyperactivity disorder
      (ADHD). The amino acid tyrosine is the precursor for synthesis of the
      catecholamines dopamine and norepinephrine, while tryptophan is the precursor of
      serotonin. A disturbed transport of tyrosine, as well as other amino acids, has
      been found in a number of other psychiatric disorders, such as schizophrenia,
      bipolar disorder and autism, when using the fibroblast cell model. Hence, the aim
      of this study was to explore whether children with ADHD may have disturbed amino
      acid transport. METHODS: Fibroblast cells were cultured from skin biopsies
      obtained from 14 boys diagnosed with ADHD and from 13 matching boys without a
      diagnosis of a developmental disorder. Transport of the amino acids tyrosine,
      tryptophan and alanine across the cell membrane was measured by the cluster tray
      method. The kinetic parameters, maximal transport capacity (V(max)) and affinity
      constant (K(m)) were determined. Any difference between the two groups was
      analyzed by Student's unpaired t-test or the Mann Whitney U test. RESULTS: The
      ADHD group had significantly decreased V(max) (p = 0.039) and K(m) (increased
      affinity) (p = 0.010) of tryptophan transport in comparison to controls. They
      also had a significantly higher V(max)of alanine transport (p = 0.031), but the
      Km of alanine transport did not differ significantly. There were no significant
      differences in any of the kinetic parameters regarding tyrosine transport in
      fibroblasts for the ADHD group. CONCLUSIONS: Tryptophan uses the same transport
      systems in both fibroblasts and at the blood brain barrier (BBB). Hence, a
      decreased transport capacity of tryptophan implies that less tryptophan is being
      transported across the BBB in the ADHD group. This could lead to deficient
      serotonin access in the brain that might cause disturbances in both the
      serotonergic and the catecholaminergic neurotransmitter systems, since these
      systems are highly interconnected. The physiological importance of an elevated
      transport capacity of alanine to the brain is not known to date.

PMID- 21942984
TI  - Measles vaccination in humanitarian emergencies: a review of recent practice.
AB  - BACKGROUND: The health needs of children and adolescents in humanitarian
      emergencies are critical to the success of relief efforts and reduction in
      mortality. Measles has been one of the major causes of child deaths in
      humanitarian emergencies and further contributes to mortality by exacerbating
      malnutrition and vitamin A deficiency. Here, we review measles vaccination
      activities in humanitarian emergencies as documented in published literature. Our
      main interest was to review the available evidence focusing on the target age
      range for mass vaccination campaigns either in response to a humanitarian
      emergency or in response to an outbreak of measles in a humanitarian context to
      determine whether the current guidance required revision based on recent
      experience. METHODS: We searched the published literature for articles published
      from January 1, 1998 to January 1, 2010 reporting on measles in emergencies. As
      definitions and concepts of emergencies vary and have changed over time, we chose
      to consider any context where an application for either a Consolidated Appeals
      Process or a Flash Appeal to the UN Central Emergency Revolving Fund (CERF)
      occurred during the period examined. We included publications from countries
      irrespective of their progress in measles control as humanitarian emergencies may
      occur in any of these contexts and as such, guidance applies irrespective of
      measles control goals. RESULTS: Of the few well-documented epidemic descriptions
      in humanitarian emergencies, the age range of cases is not limited to under 5
      year olds. Combining all data, both from preventive and outbreak response
      interventions, about 59% of cases in reports with sufficient data reviewed here
      remain in children under 5, 18% in 5-15 and 2% above 15 years. In instances where
      interventions targeted a reduced age range, several reports concluded that the
      age range should have been extended to 15 years, given that a significant
      proportion of cases occurred beyond 5 years of age. CONCLUSIONS: Measles
      outbreaks continue to occur in humanitarian emergencies due to low levels of pre
      existing population immunity. According to available published information, cases
      continue to occur in children over age 5. Preventing cases in older age groups
      may prevent younger children from becoming infected and reduce mortality in both
      younger and older age groups.

PMID- 21942985
TI  - Visualization and exploration of conserved regulatory modules using ReXSpecies 2.
AB  - BACKGROUND: The prediction of transcription factor binding sites is difficult for
      many reasons. Thus, filtering methods are needed to enrich for biologically
      relevant (true positive) matches in the large amount of computational predictions
      that are frequently generated from promoter sequences. RESULTS: ReXSpecies 2
      filters predictions of transcription factor binding sites and generates a set of
      figures displaying them in evolutionary context. More specifically, it uses
      position specific scoring matrices to search for motifs that specify
      transcription factor binding sites. It removes redundant matches and filters the
      remaining matches by the phylogenetic group that the matrices belong to. It then
      identifies potential transcriptional modules, and generates figures that
      highlight such modules, taking evolution into consideration. Module formation,
      scoring by evolutionary criteria and visual clues reduce the amount of
      predictions to a manageable scale. Identification of transcription factor binding
      sites of particular functional importance is left to expert filtering. ReXSpecies
      2 interacts with genome browsers to enable scientists to filter predictions
      together with other sequence-related data. CONCLUSIONS: Based on ReXSpecies 2, we
      derive plausible hypotheses about the regulation of pluripotency. Our tool is
      designed to analyze transcription factor binding site predictions considering
      their common pattern of occurrence, highlighting their evolutionary history.

PMID- 21942986
TI  - Integrin antagonists prevent costimulatory blockade-resistant transplant
      rejection by CD8(+)  memory T cells.
AB  - The success of belatacept in late-stage clinical trials inaugurates the arrival
      of a new class of immunosuppressants based on costimulatory blockade, an
      immunosuppression strategy that disrupts essential signals required for
      alloreactive T-cell activation. Despite having improved renal function, kidney
      transplant recipients treated with belatacept experienced increased rates of
      acute rejection. This finding has renewed focus on costimulatory blockade
      resistant rejection and specifically the role of alloreactive memory T cells in
      mediating this resistance. To study the mechanisms of costimulatory blockade
      resistant rejection and enhance the clinical efficacy of costimulatory blockade,
      we developed an experimental transplant system that models a donor-specific
      memory CD8(+)  T-cell response. After confirming that graft-specific memory T
      cells mediate costimulatory blockade-resistant rejection, we characterized the
      role of integrins in this rejection. The resistance of memory T cells to
      costimulatory blockade was abrogated when costimulatory blockade was coupled with
      either anti-VLA-4 or anti-LFA-1. Mechanistic studies revealed that in the
      presence of costimulatory blockade, anti-VLA-4 impaired T-cell trafficking to the
      graft but not memory T-cell recall effector function, whereas anti-LFA-1
      attenuated both trafficking and memory recall effector function. As antagonists
      against these integrins are clinically approved, these findings may have
      significant translational potential for future clinical transplant trials.

PMID- 21942987
TI  - Single nucleotide polymorphisms that differentiate two subpopulations of
      Salmonella enteritidis within phage type.
AB  - BACKGROUND: Salmonella Enteritidis is currently the world's leading cause of
      salmonellosis, in part because of its ability to contaminate the internal
      contents of eggs. Previous analyses have shown that it is an exceptionally clonal
      serotype, which nonetheless generates considerable phenotypic heterogeneity. Due
      to its clonality, whole genome analysis is required to find genetic determinants
      that contribute to strain heterogeneity of Salmonella Enteritidis. Comparative
      whole genome mutational mapping of two PT13a strains that varied in the ability
      to contaminate eggs and to form biofilm was achieved using a high-density tiling
      platform with primers designed from a PT4 reference genome. Confirmatory Sanger
      sequencing was used on each putative SNP identified by mutational mapping to
      confirm its presence and location as compared to the reference sequence. High
      coverage pyrosequencing was used as a supporting technology to review results.
      RESULTS: A total of 250 confirmed SNPs were detected that differentiated the
      PT13a strains. From these 250 SNPS, 247 were in the chromosome and 3 were in the
      large virulence plasmid. SNPs ranged from single base pair substitutions to a
      deletion of 215 bp. A total of 15 SNPs (3 in egg-contaminating PT13a 21046 and 12
      in biofilm forming PT13a 21027) altered coding sequences of 16 genes.
      Pyrosequencing of the two PT13a subpopulations detected 8.9% fewer SNPs than were
      detected by high-density tiling. Deletions and ribosomal gene differences were
      classes of SNPs not efficiently detected by pyrosequencing. CONCLUSIONS: These
      results increase knowledge of evolutionary trends within Salmonella enterica that
      impact the safety of the food supply. Results may also facilitate designing 2nd
      generation vaccines, because gene targets were identified that differentiate
      subpopulations with variant phenotypes. High-throughput genome sequencing
      platforms should be assessed for the ability to detect classes of SNPs
      equivalently, because each platform has different advantages and limits of
      detection.

PMID- 21942990
TI  - Knowledge and attitudes of primary healthcare patients regarding population-based
      screening for colorectal cancer.
AB  - ABSTRACT:  BACKGROUND: The aim of this study was to assess the extent of
      knowledge of primary health care (PHC) patients about colorectal cancer (CRC),
      their attitudes toward population-based screening for this disease and gender
      differences in these respects. METHODS: A questionnaire-based survey of PHC
      patients in the Balearic Islands and some districts of the metropolitan area of
      Barcelona was conducted. Individuals between 50 and 69 years of age with no
      history of CRC were interviewed at their PHC centers. RESULTS: We analyzed the
      results of 625 questionnaires, 58% of which were completed by women. Most
      patients believed that cancer diagnosis before symptom onset improved the chance
      of survival. More women than men knew the main symptoms of CRC. A total of 88.8%
      of patients reported that they would perform the fecal occult blood test (FOBT)
      for CRC screening if so requested by PHC doctors or nurses. If the FOBT was
      positive and a colonoscopy was offered, 84.9% of participants indicated that they
      would undergo the procedure, and no significant difference by gender was
      apparent. Fear of having cancer was the main reason for performance of an FOBT,
      and also for not performing the FOBT, especially in women. Fear of pain was the
      main reason for not wishing to undergo colonoscopy. Factors associated with
      reluctance to perform the FOBT were: (i) the idea that that many forms of cancer
      can be prevented by exercise and, (ii) a reluctance to undergo colonoscopy if an
      FOBT was positive. Factors associated with reluctance to undergo colonoscopy
      were: (i) residence in Barcelona, (ii) ignorance of the fact that early diagnosis
      of CRC is associated with better prognosis, (iii) no previous history of
      colonoscopy, and (iv) no intention to perform the FOBT for CRC screening.
      CONCLUSION: We identified gaps in knowledge about CRC and prevention thereof in
      PHC patients from the Balearic Islands and the Barcelona region of Spain. If
      fears about CRC screening, and CRC per se, are addressed, and if it is emphasized
      that CRC is preventable, participation in CRC screening programs may improve.

PMID- 21942989
TI  - Meta-analysis of efficacy and safety of intravenous ferric carboxymaltose
      (Ferinject) from clinical trial reports and published trial data.
AB  - BACKGROUND: Recommendations given for intravenous iron treatment are typically
      not supported by a high level of evidence. This meta-analysis addressed this by
      summarising the available date from clinical trials of ferric carboxymaltose
      using clinical trial reports and published reports. METHODS: Clinical trial
      reports were supplemented by electronic literature searches comparing ferric
      carboxymaltose with active comparators or placebo. Various outcomes were sought
      for efficacy (attainment of normal haemoglobin (Hb), increase of Hb by a defined
      amount, for example), together with measures of harm, including serious adverse
      events and deaths. RESULTS: Fourteen studies were identified with 2,348
      randomised patients exposed to ferric carboxymaltose, 832 to oral iron, 762 to
      placebo, and 384 to intravenous iron sucrose. Additional data were available from
      cohort studies. Intravenous ferric carboxymaltose was given up to the calculated
      iron deficit (up to 1,000 mg in one week) for iron deficiency anaemia secondary
      to chronic kidney disease, blood loss in obstetric and gynaecological conditions,
      gastrointestinal disease, and other conditions like heart failure. The most
      common comparator was oral iron, and trials lasted 1 to 24 weeks. Intravenous
      ferric carboxymaltose improved mean Hb, serum ferritin, and transferrin
      saturation levels; the mean end-of-trial increase over oral iron was, for Hb 4.8
      (95% confidence interval 3.3 to 6.3) g/L, for ferritin 163 (153 to 173) MUg/L,
      and for transferrin saturation 5.3% (3.7 to 6.8%). Ferric carboxymaltose was
      significantly better than comparator in achievement of target Hb increase (number
      needed to treat (NNT) 6.8; 5.3 to 9.7) and target Hb NNT (5.9; 4.7 to 8.1).
      Serious adverse events and deaths were similar in incidence in ferric
      carboxymaltose and comparators; rates of constipation, diarrhoea, and nausea or
      vomiting were lower than with oral iron. CONCLUSIONS: This review examined the
      available trials of intravenous ferric carboxymaltose using details from
      published papers and unpublished clinical trial reports. It increases the
      evidence available to support recommendations given for intravenous iron
      treatment, but there are limited trial data comparing different intravenous iron
      preparations.

PMID- 21942991
TI  - A theory-based educational intervention targeting nurses' attitudes and knowledge
      concerning cancer-related pain management: a study protocol of a quasi
      experimental design.
AB  - BACKGROUND: Pain is one of the most frequent problems among patients diagnosed
      with cancer. Despite the availability of effective pharmacological treatments,
      this group of patients often receives less than optimal treatment. Research into
      nurses' pain management highlights certain factors, such as lack of knowledge and
      attitudes and inadequate procedures for systematic pain assessment, as common
      barriers to effective pain management. However, educational interventions
      targeting nurses' pain management have shown promise. As cancer-related pain is
      also known to have a negative effect on vital aspects of the patient's life, as
      well as being commonly associated with problems such as sleep, fatigue,
      depression and anxiety, further development of knowledge within this area is
      warranted. METHODS/DESIGN: A quasi-experimental study design will be used to
      investigate whether the implementation of guidelines for systematic daily pain
      assessments following a theory-based educational intervention will result in an
      improvement in knowledge and attitude among nurses. A further aim is to
      investigate whether the intervention that targets nurses' behaviour will improve
      hospital patients' perception of pain. Data regarding nurses' knowledge and
      attitudes to pain (primary outcome), patient perception regarding pain (secondary
      outcome), together with socio-demographic variables, will be collected at
      baseline and at four weeks and 12 weeks following the intervention. DISCUSSION:
      Nursing care is nowadays acknowledged as an increasingly complicated activity and
      "nursing complexity is such that it can be seen as the quintessential complex
      intervention." To be able to change and improve clinical practice thus requires
      multiple points of attack appropriate to meet complex challenges. Consequently,
      we expect the theory-based intervention used in our quasi-experimental study to
      improve care as well as quality of life for this group of patients and we also
      envisage that evidence-based guidelines targeting this patient group's pain will
      be implemented more widely. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov
      NCT01313234.

PMID- 21942993
TI  - Long lasting phantosmia treated with venlafaxine.
AB  - Qualitative olfactory disorders such as parosmia and phantosmia are not well
      investigated. In particular, the causes and treatment options for phantosmia are
      largely unknown. We report a case of long lasting phantosmia that disappeared
      under anti-depressive treatment, raising the question to what extent certain
      forms of qualitative olfactory disorders are an early symptom of depression.

PMID- 21942992
TI  - Immunogenicity of bovine and leporine articular chondrocytes and meniscus cells.
AB  - Immune rejection is a major concern for any allogeneic or xenogeneic graft. For
      in vivo investigations of cartilage tissue engineering strategies, small animal
      models such as the leporine model are commonly employed. Many studies report
      little to no immune rejection upon allogeneic or xenogeneic implantation of
      native articular and meniscal cartilages. This study investigated whether bovine
      and leporine articular chondrocytes (ACs) and meniscus cells (MCs) have
      immunoprivileged characteristics because of their ability to stimulate
      proliferation of leporine peripheral blood mononuclear cells (PBMCs) in vitro.
      After 6 days of co-culture, none of the cell types caused a proliferative
      response in the leporine PBMCs, indicating that these cells may not elicit immune
      rejection in vivo. Reverse transcriptase polymerase chain reaction analysis for
      major histocompatibility complex class (MHC) I and II and costimulation factors
      CD80 and CD86 revealed that all cell types produced messenger RNA for MHC I and
      II, but only some were CD80 or CD86 positive, and none were positive for both
      costimulation factors. Flow cytometry found that bovine MCs and ACs displayed MHC
      II (MCs: 32.5%, ACs: 14.4%), whereas only leporine ACs were MHC II positive
      (7.5%). Although present in isolated cells, MHC I and II were not observed in
      intact bovine or leporine hyaline cartilage or meniscus tissues. Despite some
      presence of MHC II and costimulation factors, none of the cell types studied were
      able to cause PBMC proliferation. These findings indicate that bovine and
      leporine MCs and ACs share a similar immunoprivileged profile, bolstering their
      use as allogeneic and xenogeneic cell sources for engineered cartilage.

PMID- 21942988
TI  - Mitochondrial dysfunction and biogenesis: do ICU patients die from mitochondrial
      failure?
AB  - Mitochondrial functions include production of energy, activation of programmed
      cell death, and a number of cell specific tasks, e.g., cell signaling, control of
      Ca2+ metabolism, and synthesis of a number of important biomolecules. As proper
      mitochondrial function is critical for normal performance and survival of cells,
      mitochondrial dysfunction often leads to pathological conditions resulting in
      various human diseases. Recently mitochondrial dysfunction has been linked to
      multiple organ failure (MOF) often leading to the death of critical care
      patients. However, there are two main reasons why this insight did not generate
      an adequate resonance in clinical settings. First, most data regarding
      mitochondrial dysfunction in organs susceptible to failure in critical care
      diseases (liver, kidney, heart, lung, intestine, brain) were collected using
      animal models. Second, there is no clear therapeutic strategy how acquired
      mitochondrial dysfunction can be improved. Only the benefit of such therapies
      will confirm the critical role of mitochondrial dysfunction in clinical settings.
      Here we summarized data on mitochondrial dysfunction obtained in diverse
      experimental systems, which are related to conditions seen in intensive care unit
      (ICU) patients. Particular attention is given to mechanisms that cause cell death
      and organ dysfunction and to prospective therapeutic strategies, directed to
      recover mitochondrial function. Collectively the data discussed in this review
      suggest that appropriate diagnosis and specific treatment of mitochondrial
      dysfunction in ICU patients may significantly improve the clinical outcome.

PMID- 21942994
TI  - The graduate entry generation: a qualitative study exploring the factors
      influencing the career expectations and aspirations of a graduating cohort of
      graduate entry dental students in one London institution.
AB  - BACKGROUND: Dentistry in the UK has a number of new graduate-entry programmes.
      The aim of the study was to explore the motivation, career expectations and
      experiences of final year students who chose to pursue a dental career through
      the graduate entry programme route in one institution; and to explore if, and
      how, their intended career expectations and aspirations were informed by this
      choice. METHOD: In-depth interviews of 14 graduate entry students in their final
      year of study. Data were transcribed verbatim and analysed using framework
      analysis. RESULTS: There were three categories of factors influencing students'
      choice to study dentistry through graduate entry: 'push', 'pull' and 'mediating'.
      Mediating factors related to students' personal concerns and circumstances,
      whereas push and pull factors related to features of their previous and future
      careers and wider social factors. Routes to Graduate Entry study comprised:
      'early career changers', 'established career changers' and those pursuing 'routes
      to specialisation'. These routes also influenced the students' practice of
      dentistry, as students integrated skills in their dental studies, and encountered
      new challenges.Factors which students believed would influence their future
      careers included: vocational training; opportunities for specialisation or
      developing special interests and policy-related issues, together with wider
      professional and social concerns.The graduate entry programme was considered
      'hard work' but a quick route to a professional career which had much to offer.
      Students' felt more could have been made of their pre-dental studies and/or
      experience during the programme. Factors perceived as influencing students'
      future contribution to dentistry included personal and social influences. Overall
      there was strong support for the values of the NHS and 'giving back' to the
      system in their future career. CONCLUSION: Graduate entry students appear to be
      motivated to enter dentistry by a range of factors which suit their preferences
      and circumstances. They generally embrace the programme enthusiastically and seek
      to serve within healthcare, largely in the public sector. These students, who
      carry wider responsibilities, bring knowledge, skills and experience to dentistry
      which could be harnessed further during the programme. The findings suggest that
      graduate entry students, facilitated by varied career options, will contribute to
      an engaged workforce.

PMID- 21942995
TI  - Finding faults: how moral dilemmas illuminate cognitive structure.
AB  - Philosophy is rife with intractable moral dilemmas. We propose that these debates
      often exist because competing psychological systems yield different answers to
      the same problem. Consequently, philosophical debate points to the natural fault
      lines between dissociable psychological mechanisms, and as such provides a useful
      guide for cognitive neuroscience. We present two case studies from recent
      research into moral judgment: dilemmas concerning whether to harm a person in
      order to save several others, and whether to punish individuals for harms caused
      accidentally. Finally, we analyze two features of mental conflict that apparently
      contribute to philosophical discord: the insistence that one answer to a problem
      must be correct ("non-negotiability") and the absence of an independent means of
      determining the correct answer ("non-adjudicability"). Fiery Cushman thanks the
      Mind/Brain/Behavior Initiative for its generous support during the preparation of
      this work. 

PMID- 21942996
TI  - Partial sequencing of the bottle gourd genome reveals markers useful for
      phylogenetic analysis and breeding.
AB  - BACKGROUND: Bottle gourd [Lagenaria siceraria (Mol.) Standl.] is an important
      cucurbit crop worldwide. Archaeological research indicates that bottle gourd was
      domesticated more than 10,000 years ago, making it one of the earliest plants
      cultivated by man. In spite of its widespread importance and long history of
      cultivation almost nothing has been known about the genome of this species thus
      far. RESULTS: We report here the partial sequencing of bottle gourd genome using
      the 454 GS-FLX Titanium sequencing platform. A total of 150,253 sequence reads,
      which were assembled into 3,994 contigs and 82,522 singletons were generated. The
      total length of the non-redundant singletons/assemblies is 32 Mb, theoretically
      covering ~ 10% of the bottle gourd genome. Functional annotation of the sequences
      revealed a broad range of functional types, covering all the three top-level
      ontologies. Comparison of the gene sequences between bottle gourd and the model
      cucurbit cucumber (Cucumis sativus) revealed a 90% sequence similarity on
      average. Using the sequence information, 4395 microsatellite-containing sequences
      were identified and 400 SSR markers were developed, of which 94% amplified bands
      of anticipated sizes. Transferability of these markers to four other cucurbit
      species showed obvious decline with increasing phylogenetic distance. From
      analyzing polymorphisms of a subset of 14 SSR markers assayed on 44
      representative China bottle gourd varieties/landraces, a principal coordinates
      (PCo) analysis output and a UPGMA-based dendrogram were constructed. Bottle gourd
      accessions tended to group by fruit shape rather than geographic origin, although
      in certain subclades the lines from the same or close origin did tend to cluster.
      CONCLUSIONS: This work provides an initial basis for genome characterization,
      gene isolation and comparative genomics analysis in bottle gourd. The SSR markers
      developed would facilitate marker assisted breeding schemes for efficient
      introduction of desired traits.

PMID- 21942997
TI  - Prevalence of asthma and atopy in sarcoidosis.
AB  - BACKGROUND AND OBJECTIVE: We hypothesized that the prevalence of allergic
      disorders, characterized by the release of type 2 cytokines (IL-4, IL-5, IL-10),
      would be lower in sarcoidosis in which there is a dominant type 1 immune response
      (IL-2, interferon-gamma). The objective was to measure the prevalence of atopy
      and self-reported asthma in patients with sarcoidosis. METHODS: Sarcoidosis
      patients (n = 136, 72 M, age range 22-75), recruited in the outpatient setting,
      completed a modified European Community Respiratory Health Survey. 123 of these
      patients provided blood for allergy testing. RESULTS: For the cohort as a whole
      the self-reported prevalence of asthma ever (21.5%) and asthma attack in the last
      12 months (7.5%), was high as was wheezing (42.1%), breathlessness with wheeze
      (22.3%) and use of an asthma medication (13.1%). The prevalence of atopy was 34%.
      These data are not different from the previously reported prevalence of asthma
      and atopy in New Zealand. CONCLUSIONS: The same prevalence of asthma symptoms and
      atopy as in the normal population suggests that the immune system is not skewed
      away from mounting T helper type 2 immune responses in sarcoidosis.

PMID- 21942998
TI  - Members of the murine Pate family are predominantly expressed in the epididymis
      in a segment-specific fashion and regulated by androgens and other testicular
      factors.
AB  - BACKGROUND: Spermatozoa leaving the testis are not able to fertilize the egg in
      vivo. They must undergo further maturation in the epididymis. Proteins secreted
      to the epididymal lumen by the epithelial cells interact with the spermatozoa and
      enable these maturational changes, and are responsible for proper storage
      conditions before ejaculation. The present study was carried out in order to
      characterize the expression of a novel Pate (prostate and testis expression) gene
      family, coding for secreted cysteine-rich proteins, in the epididymis. METHODS:
      Murine genome databases were searched and sequence comparisons were performed to
      identify members of the Pate gene family, and their expression profiles in
      several mouse tissues were characterized by RT-PCR. Alternate transcripts were
      identified by RT-PCR, sequencing and Northern hybridization. Also, to study the
      regulation of expression of Pate family genes by the testis, quantitative (q) RT
      PCR analyses were performed to compare gene expression levels in the epididymides
      of intact mice, gonadectomized mice, and gonadectomized mice under testosterone
      replacement treatment. RESULTS: A revised family tree of Pate genes is presented,
      including a previously uncharacterized Pate gene named Pate-X, and the data
      revealed that Acrv1 and Sslp1 should also be considered as members of the Pate
      family. Alternate splicing was observed for Pate-X, Pate-C and Pate-M. All the
      Pate genes studied are predominantly expressed in the epididymis, whereas
      expression in the testis and prostate is notably lower. Loss of androgens and/or
      testicular luminal factors was observed to affect the epididymal expression of
      several Pate genes. CONCLUSIONS: We have characterized a gene cluster consisting
      of at least 14 expressed Pate gene members, including Acrv1, Sslp1 and a
      previously uncharacterized gene which we named Pate-X. The genes code for
      putatively secreted, cysteine-rich proteins with a TFP/Ly-6/uPAR domain. Members
      of the Pate gene cluster characterized are predominantly expressed in the murine
      epididymis, not in the testis or prostate, and are regulated by testicular
      factors. Similar proteins are present in venoms of several reptiles, and they are
      thought to mediate their effects by regulating certain ion channels, and are thus
      expected to have a clinical relevance in sperm maturation and epididymal
      infections.

PMID- 21942999
TI  - More support for mothers: a qualitative study on factors affecting immunisation
      behaviour in Kampala, Uganda.
AB  - BACKGROUND: The proportion of Ugandan children who are fully vaccinated has
      varied over the years. Understanding vaccination behaviour is important for the
      success of the immunisation programme. This study examined influences on
      immunisation behaviour using the attitude-social influence-self efficacy model.
      METHODS: We conducted nine focus group discussions (FGDs) with mothers and
      fathers. Eight key informant interviews (KIIs) were held with those in charge of
      community mobilisation for immunisation, fathers and mothers. Data was analysed
      using content analysis. RESULTS: Influences on the mother's immunisation
      behaviour ranged from the non-supportive role of male partners sometimes
      resulting into intimate partner violence, lack of presentable clothing which made
      mothers vulnerable to bullying, inconvenient schedules and time constraints, to
      suspicion against immunisation such as vaccines cause physical disability and/or
      death. CONCLUSIONS: Immunisation programmes should position themselves to address
      social contexts. A community programme that empowers women economically and helps
      men recognise the role of women in decision making for child health is needed.
      Increasing male involvement and knowledge of immunisation concepts among
      caretakers could improve immunisation.

PMID- 21943000
TI  - Biased gene transfer and its implications for the concept of lineage.
AB  - BACKGROUND: In the presence of horizontal gene transfer (HGT), the concepts of
      lineage and genealogy in the microbial world become more ambiguous because
      chimeric genomes trace their ancestry from a myriad of sources, both living and
      extinct. RESULTS: We present the evolutionary histories of three aminoacyl-tRNA
      synthetases (aaRS) to illustrate that the concept of organismal lineage in the
      prokaryotic world is defined by both vertical inheritance and reticulations due
      to HGT. The acquisition of a novel gene from a distantly related taxon can be
      considered as a shared derived character that demarcates a group of organisms, as
      in the case of the spirochaete Phenylalanyl-tRNA synthetase (PheRS). On the other
      hand, when organisms transfer genetic material with their close kin, the
      similarity and therefore relatedness observed among them is essentially shaped by
      gene transfer. Studying the distribution patterns of divergent genes with
      identical functions, referred to as homeoalleles, can reveal preferences for
      transfer partners. We describe the very ancient origin and the distribution of
      the archaeal homeoalleles for Threonyl-tRNA synthetases (ThrRS) and Seryl-tRNA
      synthetases (SerRS). CONCLUSIONS: Patterns created through biased HGT can be
      undistinguishable from those created through shared organismal ancestry. A re
      evaluation of the definition of lineage is necessary to reflect genetic
      relatedness due to both HGT and vertical inheritance. In most instances, HGT bias
      will maintain and strengthen similarity within groups. Only in cases where HGT
      bias is due to other factors, such as shared ecological niche, do patterns emerge
      from gene phylogenies that are in conflict with those reflecting shared
      organismal ancestry.

PMID- 21943001
TI  - Reactive oxygen species drive herpes simplex virus (HSV)-1-induced
      proinflammatory cytokine production by murine microglia.
AB  - BACKGROUND: Production of reactive oxygen species (ROS) and proinflammatory
      cytokines by microglial cells in response to viral brain infection contributes to
      both pathogen clearance and neuronal damage. In the present study, we examined
      the effect of herpes simplex virus (HSV)-1-induced, NADPH oxidase-derived ROS in
      activating mitogen-activated protein kinases (MAPKs) as well as driving cytokine
      and chemokine expression in primary murine microglia. METHODS: Oxidation of 2',
      7'-dichlorodihydrofluorescin diacetate (H2DCFDA) was used to measure production
      of intracellular ROS in microglial cell cultures following viral infection. Virus
      induced cytokine and chemokine mRNA and protein levels were assessed using real
      time RT-PCR and ELISA, respectively. Virus-induced phosphorylation of microglial
      p38 and p44/42 (ERK1/2) MAPKs was visualized using Western Blot, and levels of
      phospho-p38 were quantified using Fast Activated Cell-based ELISA (FACE assay).
      Diphenyleneiodonium (DPI) and apocynin (APO), inhibitors of NADPH oxidases, were
      used to investigate the role of virus-induced ROS in MAPK activation and
      cytokine, as well as chemokine, production. RESULTS: Levels of intracellular ROS
      were found to be highly elevated in primary murine microglial cells following
      infection with HSV and the majority of this virus-induced ROS was blocked
      following DPI and APO treatment. Correspondingly, inhibition of NADPH oxidase
      also decreased virus-induced proinflammatory cytokine and chemokine production.
      In addition, microglial p38 and p44/42 MAPKs were found to be phosphorylated in
      response to viral infection and this activation was also blocked by inhibitors of
      NADPH oxidase. Finally, inhibition of either of these ROS-induced signaling
      pathways suppressed cytokine (TNF-alpha and IL-1beta) production, while chemokine
      (CCL2 and CXCL10) induction pathways were sensitive to inhibition of p38, but not
      ERK1/2 MAPK. CONCLUSIONS: Data presented herein demonstrate that HSV infection
      induces proinflammatory responses in microglia through NADPH oxidase-dependent
      ROS and the activation of MAPKs.

PMID- 21943002
TI  - Inter-observer variability in contouring the penile bulb on CT images for
      prostate cancer treatment planning.
AB  - Several investigations have recently suggested the existence of a correlation
      between the dose received by the penile bulb (PB) and the risk of erectile
      dysfunction (ED) after radical radiotherapy for clinically localized prostate
      carcinoma. A prospective multi-Institute study (DUE-01) was implemented with the
      aim to assess the predictive parameters of ED. Previously, an evaluation of inter
      observer variations of PB contouring was mandatory in order to quantify its
      impact on PB dose-volume parameters by means of a dummy run exercise. Fifteen
      observers, from different Institutes, drew the PB on the planning CT images of
      ten patients; inter-observer variations were analysed in terms of PB volume
      variation and cranial/caudal limits. 3DCRT treatment plans were simulated to
      evaluate the impact of PB contouring inter-variability on dose-volume statistics
      parameters. For DVH analysis the values of PB mean dose and the volume of PB
      receiving more than 50 Gy and 70 Gy (V50 and V70, respectively) were considered.
      Systematic differences from the average values were assessed by the Wilcoxon
      test. Seven observers systematically overestimated or underestimated the PB
      volume with deviations from the average volumes ranging between -48% and +34% (p
      < 0.05). The analysis of the cranial and caudal borders showed a prevalence of
      random over systematic deviations. Inter-observer contouring variability strongly
      impacts on DVH parameters, although standard deviations of inter-patient
      differences were larger than inter-observer variations: 14.5 Gy versus 6.8 Gy for
      mean PB dose, 23.0% versus 11.0% and 16.8% versus 9.3% for V50 and V70
      respectively. In conclusion, despite the large inter-observer variation in
      contouring PB, a large multi-centric study may have the possibility to detect a
      possible correlation between PB % dose-volume parameters and ED. The impact of
      contouring uncertainty could be reduced by "a posteriori" contouring from a
      single observer or by introducing Magnetic Resonance Imaging (MRI) in the
      planning procedures and/or in improving the skill of observers through post-dummy
      run tutoring of those observers showing large systematic deviations from the
      mean.

PMID- 21943003
TI  - [Association of a polymorphic marker Trp719Arg of KIF6 gene with effects of
      atorvastatin and simvastatin in patients with early ischemic heart disease].
AB  - Action of statins is characterized by pronounced variability what is caused by
      effects of a multitude of factors. Main of these factors appears to be genetic
      peculiarity of patients. We studied influence of polymorphic marker Trp719Arg of
      KIF6 gene on lipid and nonlipid effects of atorvastatin and simvastatin. The
      studied genetic marker is associated with risk of development of ischemic heart
      disease and myocardial infarction as well as efficacy of therapy with statins
      according to data of a number of large multicenter studies. We examined 60 men
      with ischemic heart disease which had manifested in young age when genetic
      factors were most expressed and had special significance. Efficacy of 40 mg/day
      simvastatin did not depend on genotypes of polymorphic marker Trp719Arg of KIF6.
      Therapy with 10 mg/day atorvastatin was more effective in carriers of polymorphic
      marker Trp719Arg of KIF6 gene by action on dynamics of changes of high
      sensitivity C-reactive protein and dispersion of high density lipoprotein
      response. Increase of atorvastatin dose to 80 mg/day abolished influence of
      genotypes. Thus for the first time we discovered influence of polymorphic marker
      Trp719Arg of KIF6 gene on individual response to therapy with 10 mg/day of
      atorvastatin, while and apoA1, structural protein of high density lipoproteins
      can be considered as a marker of "fast response".

PMID- 21943004
TI  - [Effectiveness of early invasive strategy of treatment of angina of new onset].
AB  - Aim of the study was to assess effectiveness of early invasive strategy of
      treatment of angina of new onset (ANO). We conducted comparative assessment on
      invasive and noninvasive risk estimation in 106 patients admitted to
      N.V.Sklifosofsky Institute of Urgent Aid in 2003-2007. Percutaneous coronary
      interventions (PCI) on symptom related artery (SRA) within single procedure were
      carried out in 74 cases (70%), indications to coronary artery bypass surgery were
      detected in 16 cases (15%), in 16 more cases conservative treatment was used. The
      data obtained showed that it is rational to consider ANO as unstable angina in
      all cases including those without progression. Visualization of coronary arteries
      gives possibility to define significance of SRA and zone at risk of injury,
      determine indications to myocardial revascularization, and avoid inadequacy of
      noninvasive assessment of risk and choice of treatment tactics. The method of
      choice in the treatment of patients with ANO is PCI performed during single
      procedure. Detection of indications to coronary artery bypass surgery in low risk
      patients and in absence of progression confirm necessity of routine use of
      invasive strategy which provides timely pathogenetic treatment. Absence of
      indications to myocardial revascularization detected in sporadic cases provides
      possibility to avoid groundless hospitalizations.

PMID- 21943005
TI  - [The role of micro-RNA/143/145 in evolution of intra-stent restenosis].
AB  - The mechanisms of neointima formation and hyperplasia in restenosis remain non
      elucidated yet. Because micro-ribonucleic acids/143/145(micro-RNA/143 and micro
      RNA/145) participate in the regulation and sustaining of the genotype of mature
      vascular myocytes we have measured their expression in tissue content of
      restenoses taken postmortem from 5 patients who underwent angioplasty and
      subsequently died, and studied its association with actin quantity and fibrillar
      collagen type I degradation degree. It has been found that during restenosis
      progression quantity of micro-RNA/143 and micro-RNA/145 decreases in media and
      intima of coronary artery. This finding has been associated with appearance in
      coronary intima of coronary myocytes with reduced size likely of secretory
      phenotype, diminution of number of myocytes with contractile phenotype, and
      increase of quantity of denaturized collagen type I-phenomena characteristic for
      neointima hyperplasia, a substrate of intra-stent restenosis.

PMID- 21943006
TI  - [Chronic heart failure--speciale of treatment].

PMID- 21943007
TI  - [Clinico-economical aspects of application of trimetazidine MB in patients with
      chronic heart failure and cardiac rhythm disturbances].
AB  - AIM: To study clinical and pharmacoeconomical aspects of trimetazidine MD as a
      component of complex therapy of chronic heart failure (CHF) in patients with
      cardiac rhythm disturbances. MATERIAL AND METHODS: In 82 patients (67 men, 15
      women, mean age 62.2+/-7.3 years) with II-III functional class (FC) of CHF we
      studied effect of addition of therapy with trimetazidine MB to standard therapy
      on CHF FC, parameters of Holter monitoring (HM) of ECG and treadmill test. In
      analysis of HM we considered number of isolated and paired ventricular
      extrasystoles (VE), episodes of nonsustained ventricular tachycardia (VT),
      duration of episodes of ST segment depression on 24-hour ECG. Pharmacoeconomical
      analysis of 2 therapy regimes was conducted by the method of calculation of
      cost/efficacy ratio for each parameter. Stabilization of state was achieved
      before study in all patients at the background of standard therapy with
      angiotensin converting enzyme inhibitors, cardiac glycosides, diuretics, beta
      adrenoblockers. At the background of this therapy trimetazidine MB in the dose of
      70 mg/day was added to 40 patients of group 1 while 42 patients of group 2
      received standard therapy without trimetazidine MB. RESULTS: After 16 weeks of
      treatment CHF FC lowered 11% (<0.05) 10% (<0.05) in groups 1 and 2, respectively.
      According to data of HM numbers of VE decreased in group 1 by 57.6% (<0.05), in
      group 2 by 28.8% (<0.05), episodes of nonsustained VT--by 58.3% (<0,05) and 36.8%
      (<0.05), isolated VE--by 23.6% (>0.05) and 6.9% (>0.05), respectively. Duration
      of episodes of ST depression decreased 55.5% (<0.05) in group 1 and 23.3% (<0.05)
      in group 2. According to treadmill test maximal power of load in patients of
      group 1 rose 12.3% (<0.05), of group 2-6.7% (<0.05), total exercise duration rose
      16.8% (<0.05) and 82% (<0.05), respectively. Cost/efficacy ratio expressed in
      roubles per 1% efficacy calculated for CHF FC was 2694 in group 1, 4095--in group
      2; for maximal load power--2409 and 3667, respectively; for duration of episodes
      of ST segment depression--1665 and 1934, respectively; for dynamics of VE number-
      514 and 853, respectively. CONCLUSIONS: Supplementation of standard CHF therapy
      with therapy with metabolic cytoprotector trimetazidine MB allows to achieve more
      pronounced positive effect on CHF FC, exercise tolerance, and lowering of cardiac
      ectopic activity. Smallest cost efficacy ratio after addition of trimetazidine MB
      to standard therapy from pharmacoeconomical point of view evidence for advantages
      of this regime of therapy possessing smaller expenditures per unit of efficacy.

PMID- 21943008
TI  - [Parameters of central hemodynamics in patients with  typical atrial flutter
      before and after radiofrequency catheter ablation].
AB  - We present here results of dynamic assessment of morphofunctional state of the
      myocardium by the method of transthoracic echocardiography (EchoCG) in patients
      with paroxysmal and chronic forms of typical atrial flutter (AF) before and
      during one year after radiofrequency catheter ablation (RFA) of cavo-tricuspid
      isthmus, and comparison of them with analogous parameters in a group of healthy
      volunteers. Eighty six patients participated in the study. Group 1 comprised 48
      patients suffering from paroxysmal form of typical AF including 42 (87.5%) men, 6
      (12.5%) women (mean age 50.9+/-18.1 years). Group 2 consisted of 18 patients with
      permanent form of typical AF including 16 (88.9%) men and 2 (11.1%) women (mean
      age 53.6+/-9.4 years). The group of clinical comparison comprised 20 practically
      healthy persons (mean age 41.9+/-5.3 years) without structural pathology from the
      side of cardiovascular system including 15 (75.0%) men and 5 (25.0%) women. All
      group 1 and 2 patients were subjected to RFA of typical AF. In patients of groups
      1 and 2 EchoCG was carried out before and in 2, 6, and 12 months after operation
      of RFA, in control group--once. Analysis of parameters of central hemodynamicas
      in patients with typical AF detected significantly lowered values of
      characteristics of myocardial contractile function compared with the group of
      practically healthy subjects. But these parameters did not differ significantly
      between patients with different variants of clinical course of arrhythmia. It was
      established that in patients with typical AF in 2 months after conduct of
      procedure significant improvement of myocardial inotropic function and
      diminishment of dimensions of cardiac chambers was noted. In 6 months after
      fulfilled RFA values of investigated parameters approximated analogous parameters
      in the group of clinical comparison.

PMID- 21943009
TI  - [Effect of tests with dosed physical load on sinus node function and
      repolarization in children with hereditary long QT syndrome].
AB  - The study is devoted to assessment of effect of physical effort of sinus rhythm
      rate and the state of the process of repolarization in children with 1 and 2
      molecular-genetic variants of the long QT syndrome (LQT). We have shown that LQT1
      is characterized by inadequate increment of heart rate (HR) and substantial
      increase of QTc interval during exercise. In LQT2 compared with control reduction
      of HR increment also takes place while shortening of QTc interval is more
      pronounced. Delta QTc<0 is an important differential diagnostic criterion in
      patients with LQT1 and LQT2. Variatins in T wave morphology in LQT1 and LQT2
      diminish at the background of physical exercise. The use of beta-blockers
      influences relationship between length of QT interval and HR in patients with LQT
      but does not eliminate distinction from a group of patients with analogous
      variant of the syndrome not taking these drugs.

PMID- 21943010
TI  - [Antitachycardia and resynchronization devices  in the treatment of heart failure
      and prevention of  sudden death].
AB  - According to the modern ideas of the heart failure pathogenesis the noticeable
      contribution introduces ventricular dissynchrony which essence consists of the
      electrical and mechanical dissociation of different segments of the myocardium.
      In recent years the new method of cardiac resynchronization therapy has been
      worked out and achived good results. Its main purpose is the resynchronization of
      the heart by three-chamber or biventricular stimulation, which leads to an
      improvement of the effectiveness of heart activity. At the same time implanted
      cardioverter-defibrillator systems are actively used in the complex treatment of
      heart failure as a mean of sudden cardiac death prevention. In this article we
      present results of main international studies, which reveal clinical
      effectiveness of both methods for decreasing total mortality and frequency of
      hospitalizations, prolonging life span, and improving quality of life.

PMID- 21943011
TI  - [Perspectives of the use of fenofibrate in patients with type 2 diabetes
      mellitus: what is new after the ACCORD Study?].

PMID- 21943012
TI  - [Cardioneurological aspects of antiplatelet therapy in secondary prevention of
      cardiovascular diseases].
AB  - The paper reflects contemporary views of the role of antiplatelet therapy in
      secondary prevention of cardiovascular diseases in patients with coronary heart
      disease and ischemic stroke. On the basis of evidence based medicine analytical
      characteristics of all antiplatelet drugs subjected to clinical trials in the
      world are presented. Advantages and imperfectness of each agent both as
      monotherapy and used in combinations are demonstrated. Main principles of
      selection of antiplatelet drugs in patients after ischemic stroke, myocardial
      infarction, or in stable manifestations of coronary atherosclerosis are also
      given.

PMID- 21943013
TI  - [Cardiac resynchronization therapy in patients with narrow QRS].
AB  - Conduction delay affecting 30-50% of patients with NYHA class III-IV heart
      failure (HF) mainly results from left bundle branch block and leads to
      deterioration of cardiac contractility through intra- and interventricular
      dyssynchrony. Cardiac resynchronization therapy (CRT) has class I recommendation
      for the treatment of patients with severe systolic HF who have left ventricular
      ejection fraction less or equal to 35%, QRS duration greater than or equal to 120
      ms. Nevertheless some studies have shown that systolic asynchrony is present in
      27-43% of HF patients with narrow QRS complexes (defined as <120 ms). We present
      here results of CRT in 20 patients (13 male, 7 female). Main indication for CRT
      was ventricular dyssynchrony during basic cardiac rhythm or cardiac pacing
      independently of QRS width. In 4 patients width of QRS complex was less than 120
      ms, in 3 QRS varied from 120 to 149 ms pts and in 13 it was equal to or exceeded
      150 ms. CRT in patients with narrow QRS resulted in clinical improvement
      associated with increase of cardiac contractility and decrease of left
      ventricular end systolic volume. This allows to conclude that CRT can be
      beneficial for HF patients with narrow QRS and ventricular dyssynchrony.

PMID- 21943014
TI  - [Consensus of experts on the role of ethyl esters of omega-3 polyunsaturated
      fatty acids for the treatment and prevention of chronic heart failure (conclusion
      of experts meeting, June 2011)].

PMID- 21943015
TI  - [Novel Russian recommendations on arterial hypertension priority for combination
      therapy (Russian Medical Society on arterial hypertension, section of evidence
      based hypertensiology)].

PMID- 21943016
TI  - Associations between respiratory illnesses and secondhand smoke exposure in
      flight attendants: A cross-sectional analysis of the Flight Attendant Medical
      Research Institute Survey.
AB  - ABSTRACT:  BACKGROUND: Secondhand tobacco smoke (SHS) is associated with
      increased risk of respiratory illness, cancer, and cardiovascular disease. Prior
      to smoking bans on airlines in the late 1980s, flight attendants were exposed to
      a significant amount of SHS. In the present study, we examine associations
      between flight attendant SHS exposure and development of respiratory illnesses
      and cardiovascular disease. METHODS: Between December 2006 and October 2010,
      three hundred sixty-two flight attendants completed an online questionnaire with
      information regarding experience as a flight attendant, medical history, smoking
      history, and SHS exposure. Rates of illnesses in flight attendants were compared
      with an age and smoking history matched population sample from NHANES 2005-2006.
      Logistic regression analysis was used to examine the association of reported
      medical conditions and pre-ban years of exposure. RESULTS: Compared with the
      sample from NHANES 2005-2006, flight attendants had increased prevalence of
      chronic bronchitis (11.7% vs. 7.2%, p < 0.05), emphysema/COPD (3.2% vs. 0.9%, p <
      0.03), and sinus problems (31.5% vs. 20.9%, p < 0.002), despite a lower
      prevalence of medical illnesses including high blood pressure, diabetes, high
      cholesterol, heart failure, cancer, and thyroid disease. Amongst flight
      attendants who reported never smoking over their lifetimes, there was not a
      significant association between years of service as a flight attendant in the pre
      smoking ban era and illnesses. However, in this same group, there was a
      significantly increased risk of daily symptoms (vs. no symptoms) of nasal
      congestion, throat, or eye irritation per 10-year increase of years of service as
      a flight attendant prior to the smoking ban (OR 2.14, 95% CI 1.41 - 3.24).
      CONCLUSIONS: Flight attendants experience increased rates of respiratory
      illnesses compared to a population sample. The frequency of symptoms of nasal
      congestion, throat or eye irritation is associated with occupational SHS exposure
      in the pre-smoking ban era.

PMID- 21943017
TI  - Hepatic cerebrospinal fluid pseudocyst mimicking hydatid liver disease: a case
      report.
AB  - INTRODUCTION: An abdominal pseudocyst is a rare complication of a ventriculo
      peritoneal shunt. Etiological factors include infection, obstruction and
      dislodgement. This is the first report of a hepatic cerebrospinal fluid
      pseudocyst mimicking hydatid liver disease. CASE PRESENTATION: We report the case
      of an 18-year-old Caucasian male patient who presented with a hepatic pseudocyst
      secondary to a ventriculo-peritoneal shunt, misdiagnosed as hydatid disease of
      the liver. CONCLUSION: Hepatic pseudocysts, a rare complication of a ventriculo
      peritoneal shunt, have similar clinical and radiological characteristics to those
      of hydatid liver disease. The formation of a pseudocyst should always be
      considered in patients with ventriculo-peritoneal shunts in situ.

PMID- 21943018
TI  - A single-nucleotide polymorphism in TP53 may be a genetic risk factor for Iranian
      patients with idiopathic male infertility.
AB  - Male infertility is a heterogeneous disorder that contributes to the impairment
      of spermatogenesis. The purpose of this study was to assess whether tumour
      suppressor p53 gene (Tp53) polymorphism is associated with idiopathic male
      infertility in the Iranian population. The prevalence of G -> C substitution at
      codon 72 in exon 4 was determined in 110 idiopathic infertile azoo-/oligospermic
      patients and 180 fertile healthy control men. PCR-restriction fragment
      polymorphism analysis was employed to determine the genotypes. PCR amplicons were
      subjected to restriction digestion with Bstu1 and separated by gel
      electrophoresis. The Arg/Arg genotype was found more frequently among men with
      idiopathic infertility (32.7%) than among controls (17.7%). No significant
      difference was observed between Pro/Pro genotype and Arg/Arg + Arg/Pro genotypes
      among men with idiopathic infertility and controls (P = 0.11; OR: 0.36; 95% CI:
      0.36-1.10). In contrast, a significant difference was observed in the comparison
      of the Arg/Arg genotype and Arg/Pro + Pro/Pro genotypes among patients and
      controls (P = 0.004; OR: 2.25; 95% CI: 1.29-3.90). Allele frequency evaluation
      suggested a significantly higher incidence of the Arg allele among infertile men
      compared with controls (56% versus 44%; OR: 1.6; 95% CI: 0.92-2.80). In
      conclusion, arginine allele appears to be at greater risk of developing
      idiopathic infertility in Iranian men.

PMID- 21943019
TI  - A holistic phylogeny of the coronin gene family reveals an ancient origin of the
      tandem-coronin, defines a new subfamily, and predicts protein function.
AB  - BACKGROUND: Coronins belong to the superfamily of the eukaryotic-specific WD40
      repeat proteins and play a role in several actin-dependent processes like
      cytokinesis, cell motility, phagocytosis, and vesicular trafficking. Two major
      types of coronins are known: First, the short coronins consisting of an N
      terminal coronin domain, a unique region and a short coiled-coil region, and
      secondly the tandem coronins comprising two coronin domains. RESULTS: 723 coronin
      proteins from 358 species have been identified by analyzing the whole-genome
      assemblies of all available sequenced eukaryotes (March 2011). The organisms
      analyzed represent most eukaryotic kingdoms but also cover every taxon several
      times to provide a better statistical sampling. The phylogenetic tree of the
      coronin domains based on the Bayesian method is in accordance with the most
      recent grouping of the major kingdoms of the eukaryotes and also with the
      grouping of more recently separated branches. Based on this "holistic" approach
      the coronins group into four classes: class-1 (Type I) and class-2 (Type II) are
      metazoan/choanoflagellate specific classes, class-3 contains the tandem-coronins
      (Type III), and the new class-4 represents the coronins fused to villin (Type
      IV). Short coronins from non-metazoans are equally related to class-1 and class-2
      coronins and thus remain unclassified. CONCLUSIONS: The coronin class
      distribution suggests that the last common eukaryotic ancestor possessed a single
      and a tandem-coronin, and most probably a class-4 coronin of which homologs have
      been identified in Excavata and Opisthokonts although most of these species
      subsequently lost the class-4 homolog. The most ancient short coronin already
      contained the trimerization motif in the coiled-coil domain.

PMID- 21943020
TI  - Payments and quality of care in private for-profit and public hospitals in
      Greece.
AB  - BACKGROUND: Empirical evidence on how ownership type affects the quality and cost
      of medical care is growing, and debate on these topics is ongoing. Despite the
      fact that the private sector is a major provider of hospital services in Greece,
      little comparative information on private versus public sector hospitals is
      available. The aim of the present study was to describe and compare the operation
      and performance of private for-profit (PFP) and public hospitals in Greece,
      focusing on differences in nurse staffing rates, average lengths of stay (ALoS),
      and Social Health Insurance (SHI) payments for hospital care per patient
      discharged. METHODS: Five different datasets were prepared and analyzed, two of
      which were derived from information provided by the National Statistical Service
      (NSS) of Greece and the other three from data held by the three largest SHI
      schemes in the country. All data referred to the 3-year period from 2001 to 2003.
      RESULTS: PFP hospitals in Greece are smaller than public hospitals, with lower
      patient occupancy, and have lower staffing rates of all types of nurses and
      highly qualified nurses compared with public hospitals. Calculation of ALoS using
      NSS data yielded mixed results, whereas calculations of ALoS and SHI payments
      using SHI data gave results clearly favoring the public hospital sector in terms
      of cost-efficiency; in all years examined, over all specialties and all SHI
      schemes included in our study, unweighted ALoS and SHI payments for hospital care
      per discharge were higher for PFP facilities. CONCLUSIONS: In a mixed healthcare
      system, such as that in Greece, significant performance differences were observed
      between PFP and public hospitals. Close monitoring of healthcare provision by
      hospital ownership type will be essential to permit evidence-based decisions on
      the future of the public/private mix in terms of healthcare provision.

PMID- 21943021
TI  - Unveiling novel genes upregulated by both rhBMP2 and rhBMP7 during early
      osteoblastic transdifferentiation of C2C12 cells.
AB  - FINDINGS: We set out to analyse the gene expression profile of pre-osteoblastic
      C2C12 cells during osteodifferentiation induced by both rhBMP2 and rhBMP7 using
      DNA microarrays. Induced and repressed genes were intercepted, resulting in 1,318
      induced genes and 704 repressed genes by both rhBMP2 and rhBMP7. We selected and
      validated, by RT-qPCR, 24 genes which were upregulated by rhBMP2 and rhBMP7; of
      these, 13 are related to transcription (Runx2, Dlx1, Dlx2, Dlx5, Id1, Id2, Id3,
      Fkhr1, Osx, Hoxc8, Glis1, Glis3 and Cfdp1), four are associated with cell
      signalling pathways (Lrp6, Dvl1, Ecsit and PKCdelta) and seven are associated
      with the extracellular matrix (Ltbp2, Grn, Postn, Plod1, BMP1, Htra1 and IGFBP
      rP10). The novel identified genes include: Hoxc8, Glis1, Glis3, Ecsit, PKCdelta,
      LrP6, Dvl1, Grn, BMP1, Ltbp2, Plod1, Htra1 and IGFBP-rP10. BACKGROUND: BMPs (bone
      morphogenetic proteins) are members of the TGFbeta (transforming growth factor
      beta) super-family of proteins, which regulate growth and differentiation of
      different cell types in various tissues, and play a critical role in the
      differentiation of mesenchymal cells into osteoblasts. In particular, rhBMP2 and
      rhBMP7 promote osteoinduction in vitro and in vivo, and both proteins are
      therapeutically applied in orthopaedics and dentistry. CONCLUSION: Using DNA
      microarrays and RT-qPCR, we identified both previously known and novel genes
      which are upregulated by rhBMP2 and rhBMP7 during the onset of osteoblastic
      transdifferentiation of pre-myoblastic C2C12 cells. Subsequent studies of these
      genes in C2C12 and mesenchymal or pre-osteoblastic cells should reveal more
      details about their role during this type of cellular differentiation induced by
      BMP2 or BMP7. These studies are relevant to better understanding the molecular
      mechanisms underlying osteoblastic differentiation and bone repair.

PMID- 21943023
TI  - Geo-mapping of caries risk in children and adolescents - a novel approach for
      allocation of preventive care.
AB  - BACKGROUND: Dental caries in children is unevenly distributed within populations
      with a higher burden in low socio-economy groups. Thus, tools are needed to
      allocate resources and establish evidence-based programs that meet the needs of
      those at risk. The aim of the study was to apply a novel concept for presenting
      epidemiological data based on caries risk in the region of Halland in southwest
      Sweden, using geo-maps. METHODS: The study population consisted of 46,536
      individuals between 3-19 years of age (75% of the eligible population) from whom
      caries data were reported in 2010. Reported dmfs/DMFS>0 for an individual was
      considered as the primary caries outcome. Each study individual was geo-coded
      with respect to his/her residence parish. A parish-specific relative risk (RR)
      was calculated as the observed-to-expected ratio, where the expected number of
      individuals with dmfs/DMFS>0 was obtained from the age- and sex-specific caries
      (dmfs/DMFS>0) rates for the total study population. Smoothed caries risk geo
      maps, along with corresponding statistical certainty geo-maps, were produced by
      using the free software Rapid Inquiry Facility and the ESRI(r) ArcGIS system.
      RESULTS: The geo-maps of preschool children (3-6 years), schoolchildren (7-11
      years) and adolescents (12-19 years) displayed obvious geographical variations in
      caries risk, albeit most marked among the preschoolers. Among the preschool
      children the smoothed relative risk (SmRR) varied from 0.33 to 2.37 in different
      parishes. With increasing age, the contrasts seemed to diminish although the
      gross geographical risk pattern persisted also among the adolescents (SmRR range
      0.75-1.20). CONCLUSION: Geo-maps based on caries risk may provide a novel option
      to allocate resources and tailor supportive and preventive measures within
      regions with sections of the population with relatively high caries rates.

PMID- 21943022
TI  - Exposure to statins and risk of common cancers: a series of nested case-control
      studies.
AB  - BACKGROUND: Many studies and meta-analyses have investigated the effects of
      statins on cancer incidence but without showing consistent effects. METHODS: A
      series of nested case-control studies was conducted covering 574 UK general
      practices within the QResearch database. Cases were patients with primary cancers
      diagnosed between 1998 and 2008. The associations between statin use and risk of
      ten site-specific cancers were estimated with conditional logistic regression
      adjusted for co-morbidities, smoking status, socio-economic status, and use of
      non-steroidal anti-inflammatory drugs, cyclo-oxygenase-2 inhibitors and aspirin.
      RESULTS: 88125 cases and 362254 matched controls were analysed. The adjusted odds
      ratio for any statin use and cancer at any site were 1.01 (95%CI 0.99 to 1.04).
      For haematological malignancies there was a significant reduced risk associated
      with any statin use (odds ratio 0.78, 95%CI 0.71 to 0.86). Prolonged (more than 4
      years) use of statins was associated with a significantly increased risk of
      colorectal cancer (odds ratio 1.23, 95%CI 1.10 to 1.38), bladder cancer (odds
      ratio 1.29, 95%CI 1.08 to 1.54) and lung cancer (odds ratio 1.18, 95%CI 1.05 to
      1.34). There were no significant associations with any other cancers. CONCLUSION:
      In this large population-based case-control study, prolonged use of statins was
      not associated with an increased risk of cancer at any of the most common sites
      except for colorectal cancer, bladder cancer and lung cancer, while there was a
      reduced risk of haematological malignancies.

PMID- 21943024
TI  - The Aspergillus giganteus antifungal protein AFPNN5353 activates the cell wall
      integrity pathway and perturbs calcium homeostasis.
AB  - BACKGROUND: The antifungal protein AFPNN5353 is a defensin-like protein of
      Aspergillus giganteus. It belongs to a group of secretory proteins with low
      molecular mass, cationic character and a high content of cysteine residues. The
      protein inhibits the germination and growth of filamentous ascomycetes, including
      important human and plant pathogens and the model organsims Aspergillus nidulans
      and Aspergillus niger. RESULTS: We determined an AFPNN5353 hypersensitive
      phenotype of non-functional A. nidulans mutants in the protein kinase C
      (Pkc)/mitogen-activated protein kinase (Mpk) signalling pathway and the induction
      of the alpha-glucan synthase A (agsA) promoter in a transgenic A. niger strain
      which point at the activation of the cell wall integrity pathway (CWIP) and the
      remodelling of the cell wall in response to AFPNN5353. The activation of the CWIP
      by AFPNN5353, however, operates independently from RhoA which is the central
      regulator of CWIP signal transduction in fungi.Furthermore, we provide evidence
      that calcium (Ca2+) signalling plays an important role in the mechanistic
      function of this antifungal protein. AFPNN5353 increased about 2-fold the
      cytosolic free Ca2+ ([Ca2+]c) of a transgenic A. niger strain expressing codon
      optimized aequorin. Supplementation of the growth medium with CaCl2 counteracted
      AFPNN5353 toxicity, ameliorated the perturbation of the [Ca2+]c resting level and
      prevented protein uptake into Aspergillus sp. cells. CONCLUSIONS: The present
      study contributes new insights into the molecular mechanisms of action of the A.
      giganteus antifungal protein AFPNN5353. We identified its antifungal activity,
      initiated the investigation of pathways that determine protein toxicity, namely
      the CWIP and the Ca2+ signalling cascade, and studied in detail the cellular
      uptake mechanism in sensitive target fungi. This knowledge contributes to define
      new potential targets for the development of novel antifungal strategies to
      prevent and combat infections of filamentous fungi which have severe negative
      impact in medicine and agriculture.

PMID- 21943025
TI  - Accelerating drug discovery for Alzheimer's disease: best practices for
      preclinical animal studies.
AB  - Animal models have contributed significantly to our understanding of the
      underlying biological mechanisms of Alzheimer's disease (AD). As a result, over
      300 interventions have been investigated and reported to mitigate pathological
      phenotypes or improve behavior in AD animal models or both. To date, however,
      very few of these findings have resulted in target validation in humans or
      successful translation to disease-modifying therapies. Challenges in translating
      preclinical studies to clinical trials include the inability of animal models to
      recapitulate the human disease, variations in breeding and colony maintenance,
      lack of standards in design, conduct and analysis of animal trials, and
      publication bias due to under-reporting of negative results in the scientific
      literature. The quality of animal model research on novel therapeutics can be
      improved by bringing the rigor of human clinical trials to animal studies.
      Research communities in several disease areas have developed recommendations for
      the conduct and reporting of preclinical studies in order to increase their
      validity, reproducibility, and predictive value. To address these issues in the
      AD community, the Alzheimer's Drug Discovery Foundation partnered with Charles
      River Discovery Services (Morrisville, NC, USA) and Cerebricon Ltd. (Kuopio,
      Finland) to convene an expert advisory panel of academic, industry, and
      government scientists to make recommendations on best practices for animal
      studies testing investigational AD therapies. The panel produced recommendations
      regarding the measurement, analysis, and reporting of relevant AD targets, th
      choice of animal model, quality control measures for breeding and colony
      maintenance, and preclinical animal study design. Major considerations to
      incorporate into preclinical study design include a priori hypotheses,
      pharmacokinetics-pharmacodynamics studies prior to proof-of-concept testing,
      biomarker measurements, sample size determination, and power analysis. The panel
      also recommended distinguishing between pilot 'exploratory' animal studies and
      more extensive 'therapeutic' studies to guide interpretation. Finally, the panel
      proposed infrastructure and resource development, such as the establishment of a
      public data repository in which both positive animal studies and negative ones
      could be reported. By promoting best practices, these recommendations can improve
      the methodological quality and predictive value of AD animal studies and make the
      translation to human clinical trials more efficient and reliable.

PMID- 21943026
TI  - HIV surveillance in a large, community-based study: results from the pilot study
      of Project Accept (HIV Prevention Trials Network 043).
AB  - BACKGROUND: Project Accept is a community randomized, controlled trial to
      evaluate the efficacy of community mobilization, mobile testing, same-day
      results, and post-test support for the prevention of HIV infection in Thailand,
      Tanzania, Zimbabwe, and South Africa. We evaluated the accuracy of in-country HIV
      rapid testing and determined HIV prevalence in the Project Accept pilot study.
      METHODS: Two HIV rapid tests were performed in parallel in local laboratories. If
      the first two rapid tests were discordant (one reactive, one non-reactive), a
      third HIV rapid test or enzyme immunoassay was performed. Samples were designated
      HIV NEG if the first two tests were non-reactive, HIV DISC if the first two tests
      were discordant, and HIV POS if the first two tests were reactive. Samples were
      re-analyzed in the United States using a panel of laboratory tests. RESULTS: HIV
      infection status was correctly determined based on-in country testing for 2,236
      (99.5%) of 2,247 participants [7 (0.37%) of 1,907 HIV NEG samples were HIV
      positive; 2 (0.63%) of 317 HIV POS samples were HIV-negative; 2 (8.3%) of 24 HIV
      DISC samples were incorrectly identified as HIV-positive based on the in-country
      tie-breaker test]. HIV prevalence was: Thailand: 0.6%, Tanzania: 5.0%, Zimbabwe
      14.7%, Soweto South Africa: 19.4%, Vulindlela, South Africa: 24.4%, (overall
      prevalence: 14.4%). CONCLUSIONS: In-country testing based on two HIV rapid tests
      correctly identified the HIV infection status for 99.5% of study participants;
      most participants with discordant HIV rapid tests were not infected. HIV
      prevalence varied considerably across the study sites (range: 0.6% to 24.4%).
      TRIAL REGISTRATION: ClinicalTrials.gov registry number NCT00203749.

PMID- 21943028
TI  - Disinhibition: more than a misnomer.
AB  - Despite great progress in the science of social cognition, the old Victorian
      notion of disinhibition is entrenched in our current thinking. According to this
      notion, the frontal lobes serve to inhibit the subcortical structures, and with
      the release of such inhibition, innate behaviors are released. This paper makes a
      case that the notion of disinhibition is more than a problem of semantics and is
      rooted in an erroneous, social Darwinistic view of brain organization as a
      hierarchical and dichotomous order between cortical and subcortical structures,
      which has no anchorage in the hardwiring of the brain neuroanatomy that suggests
      a mutually reciprocal relationship between these structures. 

PMID- 21943027
TI  - The PROMISE study: a phase 2b multicenter study of voclosporin (ISA247) versus
      tacrolimus in de novo kidney transplantation.
AB  - Voclosporin (VCS, ISA247) is a novel calcineurin inhibitor being developed for
      organ transplantation. PROMISE was a 6-month, multicenter, randomized, open-label
      study of three ascending concentration-controlled groups of VCS (low, medium and
      high) compared to tacrolimus (TAC) in 334 low-risk renal transplant recipients.
      The primary endpoint was demonstration of noninferiority of biopsy proven acute
      rejection (BPAR) rates. Secondary objectives included renal function, new onset
      diabetes after transplantation (NODAT), hypertension, hyperlipidemia and
      pharmacokinetic-pharmacodynamic evaluation. The incidence of BPAR in the VCS
      groups (10.7%, 9.1% and 2.3%, respectively) was noninferior to TAC (5.8%). The
      incidence of NODAT for VCS was 1.6%, 5.7% and 17.7% versus 16.4% in TAC (low-dose
      VCS, p = 0.03). Nankivell estimated glomerular filtration rate was respectively:
      71, 72, 68 and 69 mL/min, statistically lower in the high-dose group, p = 0.049.
      The incidence of hypertension and adverse events was not different between the
      VCS groups and TAC. VCS demonstrated an excellent correlation between trough and
      area under the curve (r(2) = 0.97) and no difference in mycophenolic acid
      exposure compared to TAC. This 6-month study shows VCS to be as efficacious as
      TAC in preventing acute rejection with similar renal function in the low- and
      medium-exposure groups, and potentially associated with a reduced incidence of
      NODAT.

PMID- 21943031
TI  - Performance of the density matrix functional theory in the quantum theory of
      atoms in molecules.
AB  - The generalization to arbitrary molecular geometries of the energetic
      partitioning provided by the atomic virial theorem of the quantum theory of atoms
      in molecules (QTAIM) leads to an exact and chemically intuitive energy
      partitioning scheme, the interacting quantum atoms (IQA) approach, that depends
      on the availability of second-order reduced density matrices (2-RDMs). This work
      explores the performance of this approach in particular and of the QTAIM in
      general with approximate 2-RDMs obtained from the density matrix functional
      theory (DMFT), which rests on the natural expansion (natural orbitals and their
      corresponding occupation numbers) of the first-order reduced density matrix (1
      RDM). A number of these functionals have been implemented in the promolden code
      and used to perform QTAIM and IQA analyses on several representative molecules
      and model chemical reactions. Total energies, covalent intra- and interbasin
      exchange-correlation interactions, as well as localization and delocalization
      indices have been determined with these functionals from 1-RDMs obtained at
      different levels of theory. Results are compared to the values computed from the
      exact 2-RDMs, whenever possible.

PMID- 21943030
TI  - Evaluating learning and attitudes on tissue engineering: a study of children
      viewing animated digital dome shows detailing the biomedicine of tissue
      engineering.
AB  - Informal science education creates opportunities for the general public to learn
      about complex health and science topics. Tissue engineering is a fast-growing
      field of medical science that combines advanced chemistries to create synthetic
      scaffolds, stem cells, and growth factors that individually or in combination can
      support the bodies own healing powers to remedy a range of maladies. Health
      literacy about this topic is increasingly important as our population ages and as
      treatments become more technologically advanced. We are using a science center
      planetarium as a projection space to engage and educate the public about the
      science and biomedical research that supports tissue engineering. The purpose of
      this study was to test the effectiveness of the films that we have produced for
      part of the science center planetarium demographic, specifically children ranging
      in age from 7 to 16 years. A two-group pre- and post-test design was used to
      compare children's learning and attitude changes in response to the two versions
      of the film. One version uses traditional voice-over narration; the other version
      uses dialog between two animated characters. The results of this study indicate
      that children demonstrated increases in knowledge of the topic with either film
      format, but preferred the animated character version. The percentage change in
      children's scores on the knowledge questions given before and after viewing the
      show exhibited an improvement from 23% correct to 61% correct on average. In
      addition, many of the things that the children reported liking were part of the
      design process of the art-science collaboration. Other results indicated that
      before viewing the shows 77% of the children had not even heard about tissue
      engineering and only 17% indicated that they were very interested in it, whereas
      after viewing the shows, 95% indicated that tissue engineering was a good idea.
      We also find that after viewing the show, 71% of the children reported that the
      show made them think, 75% enjoyed it, and 89% felt that they learned something.
      We discuss the potential impact the films might have on public knowledge, health
      literacy, and attitudes toward the science of tissue engineering.

PMID- 21943029
TI  - Prevalence and socioeconomic correlates of overweight and obesity among Pakistani
      primary school children.
AB  - BACKGROUND: Childhood obesity is becoming an equally challenging, yet under
      recognized, problem in developing countries including Pakistan. Children and
      adolescents are worst affected with an estimated 10% of the world's school-going
      children being overweight and one quarter of these being obese. The study aimed
      to assess prevalence and socioeconomic correlates of overweight and obesity, and
      trend in prevalence statistics, among Pakistani primary school children. METHODS:
      A population-based cross-sectional study was conducted with a representative
      multistage cluster sample of 1860 children aged 5-12 years in Lahore, Pakistan.
      Overweight (> + 1SD) and obesity (> + 2SD) were defined using the World Health
      Organization child growth reference 2007. Chi-square test was used as the test of
      trend. Linear regression was used to examine the predictive power of independent
      variables in relation to BMI. Logistic regression was used to quantify the
      independent predictors for overweight and adjusted odds ratios (aOR) with 95%
      confidence intervals (CI) were obtained. All regression analyses were controlled
      for age and gender and statistical significance was considered at P < 0.05.
      RESULTS: Seventeen percent (95% CI 15.4-18.8) children were overweight and 7.5%
      (95% CI 6.5-8.7) were obese. Higher prevalence of obesity was observed among boys
      than girls (P = 0.028), however, there was no gender disparity in overweight
      prevalence. Prevalence of overweight showed a significantly increasing trend with
      grade (P < 0.001). Children living in the urban area with high socioeconomic
      status (SES) were significantly at risk for being overweight and obese (both P <
      0.001) as compared to children living in the urban area with lower SES and rural
      children. Being in higher grade (aOR 2.39, 95% CI 1.17-4.90) and living in the
      urban area with higher SES (aOR 18.10, 95% CI 10.24-32.00) independently
      predicted the risk of being overweight. CONCLUSION: Alarmingly rapid rise in
      overweight and obesity among Pakistani primary school children was observed,
      especially among the affluent urban population. The findings support the urgent
      need for National preventive strategy for childhood obesity and targeted
      interventions tailored to local circumstances with meaningful involvement of
      communities.

PMID- 21943032
TI  - Docetaxel- and 5-FU-concurrent radiotherapy in patients presenting unresectable
      locally advanced pancreatic cancer: a FNCLCC-ACCORD/0201 randomized phase II
      trial's pre-planned analysis and case report of a 5.5-year disease-free survival.
AB  - BACKGROUND: To explore possible improvement in the treatment of locally advanced
      pancreatic carcinoma (LAPC) we performed a randomized, non-comparative phase II
      study evaluating docetaxel - plus either daily continuous 5 FU or weekly
      cisplatin concurrent to radiotherapy. We report here the results of the docetaxel
      plus 5 FU regimen stopped according to the interim analysis. The docetaxel plus
      cisplatin arm was continued. METHODS: Forty (40) chemotherapy-naive patients with
      unresectable LAPC were randomly assigned (1:1) to either continuous fluorouracil
      (5-FU) 200 mg/m(2)/day (protracted IV) and docetaxel (DCT) 20 mg/m(2)/week or DCT
      20 mg/m2 and cisplatin (CDDP) 20 mg/m(2), plus concurrent radiotherapy for a
      period of 6 weeks. The radiation dose to the primary tumor was 54 Gy in 30
      fractions. The trial's primary endpoint was the 6-month crude non-progression
      rate (NPR). Secondary endpoints were tolerance, objective response rate, and
      overall survival. Accrual was to be stopped if at 6 months more than 13 disease
      progressions were observed in 20 patients. RESULTS: Eighteen (18) progressions
      occurred at 6 months in the 5-FU-DCT arm. Six-month NPR was 10% (95%CI: 0-23).
      Six and 12-month survivals were 85% (95%CI: 64-95) and 40% (95%CI: 22-61); median
      overall survival was 10.1 months. Median progression-free survival was 4.3
      months. We report the case of one patient who was amenable to surgery and has
      been in complete response (CR) for 5.5 years. Toxicities grade >= 3 were reported
      in 75% of patients; no treatment-related death occurred. Severe toxicities were
      mainly vomiting (35%), abdominal pain (10%) and fatigue (10%). CONCLUSIONS:
      Combination of 5-FU, docetaxel and radiotherapy has inadequate efficacy in the
      treatment of LAPC despite good tolerance for the 5-FU-DCT regimen. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT00112697.

PMID- 21943034
TI  - Rapidly fatal neuropathies and an ALS clinical presentation.
AB  - OBJECTIVES - The objective of this report is to describe patients with an
      unusually severe, rapidly fatal acquired polyneuropathy. METHODS - The clinical,
      electrodiagnostic (EDX), laboratory, and pathological findings in three patients
      with a distinctive form of neuropathic illness are discussed. RESULTS - Three
      patients, ages 67, 54, and 50, had clinical findings that met accepted clinical
      criteria for amyotrophic lateral sclerosis (ALS) - definite in two and probable
      in one. The EDX studies in these patients had abnormalities that would be highly
      atypical for ALS. There were features consistent with an asymmetrical, non-length
      dependent process as well findings consistent with demyelination - features
      consistent with a chronic acquired polyneuropathy. All patients had a rapidly
      progressive course with death because of respiratory failure in 4-30 months. The
      patients did not respond to immunomodulating therapies. Extensive evaluations in
      these patients did not reveal a cause for the patients' neuropathies. Postmortem
      examination in two of the patients did not reveal evidence for ALS. In one of
      these patients, there were pathological findings thought possibly consistent with
      an immunologically mediated process. CONCLUSION - This report emphasizes the
      importance of considering other diagnoses in patients who clinically appear to
      have ALS and raise the specter of an as of yet poorly understood, severe
      neuropathic illness.

PMID- 21943033
TI  - Lipocalin 2 in the central nervous system host response to systemic
      lipopolysaccharide administration.
AB  - BACKGROUND: Lipocalin 2 (Lcn2) is a bacteriostatic factor that may also modulate
      cellular function, however, little is known concerning the expression or role of
      Lcn2 in CNS inflammation. Therefore, here we investigated the regulation and
      possible function of Lcn2 in the CNS following peripheral lipopolysaccharide
      (LPS) injection in mice. METHODS: A murine model for systemic endotoxemia was
      used in this study. Wild type or Lcn2 KO mice (both genotypes C57BL/6 strain)
      were given either a single or dual, staggered intraperitoneal injections of
      purified E. coli LPS or vehicle alone. The brain was examined for the expression
      and location of Lcn2 mRNA and protein and various markers for neuroinflammation
      were analyzed. RESULTS: Although undetectable under physiological conditions,
      both Lcn2 mRNA and protein were induced to high levels in the brain after LPS
      injection. By contrast, RNA corresponding to the putative Lcn2 (termed 24p3R)
      receptor was present at high levels in the normal brain and remained unaltered by
      LPS injection. Differences between Lcn2 and 24p3R mRNA expression were found at
      the anatomic and cellular level. Endothelial cells, microglia and the choroid
      plexus but not neurons were identified as the main cellular sources for Lcn2 mRNA
      in the CNS. By contrast, 24p3R mRNA was detected in neurons and the choroid
      plexus only. Lcn2 protein was found to have a similar cellular localization as
      the corresponding RNA transcripts with the exception that subsets of neurons were
      also strongly positive. Various inflammatory, glial, and iron handling markers
      were analyzed and found to have similar alterations between WT and Lcn2 KO
      animals. CONCLUSIONS: 1) Lcn2 production is strongly induced in the CNS by
      systemic LPS injection, 2) in addition to Lcn2 production at key gateways of
      bacterial entry to the CNS, neurons may be a target for the actions of Lcn2,
      which is apparently taken up by these cells, and 3) the cellular functions of
      Lcn2 in the CNS remain enigmatic.

PMID- 21943035
TI  - Accidental natalizumab administration to the third trimester of pregnancy in an
      adolescent patient with multiple sclerosis.
AB  - BACKGROUND: Natalizumab is neither licensed for the use in adolescents nor during
      pregnancy. There are no reports of accidental natalizumab exposure during
      pregnancy continued as long as to the third trimester of pregnancy. AIMS: We
      report the outcome of pregnancy in a 17-year-old adolescent patient with multiple
      sclerosis (MS) treated with natalizumab from the age of 16, who was diagnosed to
      be pregnant in the 31st gestational week (gw) of pregnancy. To our knowledge,
      this report describes the first patient receiving natalizumab to the third
      trimester of pregnancy. CASE REPORT:   Because of high relapse activity,
      natalizumab treatment was administered in an adolescent patient with MS.
      Pregnancy was diagnosed in the 31st gw after 17 natalizumab infusions, seven of
      them accidentally during pregnancy. RESULTS: Pre- and postnatal development of
      the child was normal. CONCLUSIONS: The case reported indicates that accidentally
      continued natalizumab treatment until few weeks before delivery may have no
      negative impact on the developing foetus.

PMID- 21943036
TI  - Interleukin-17 and -23 levels in amyotrophic lateral sclerosis.

PMID- 21943038
TI  - Causes of death and demographic characteristics of victims of meteorological
      disasters in Korea from 1990 to 2008.
AB  - BACKGROUND: Meteorological disasters are an important component when considering
      climate change issues that impact morbidity and mortality rates. However, there
      are few epidemiological studies assessing the causes and characteristics of
      deaths from meteorological disasters. The present study aimed to analyze the
      causes of death associated with meteorological disasters in Korea, as well as
      demographic and geographic vulnerabilities and their changing trends, to
      establish effective measures for the adaptation to meteorological disasters.
      METHODS: Deaths associated with meteorological disasters were examined from 2,045
      cases in Victim Survey Reports prepared by 16 local governments from 1990 to
      2008. Specific causes of death were categorized as drowning, structural collapse,
      electrocution, lightning, fall, collision, landslide, avalanche, deterioration of
      disease by disaster, and others. Death rates were analyzed according to the
      meteorological type, specific causes of death, and demographic and geographic
      characteristics. RESULTS: Drowning (60.3%) caused the greatest number of deaths
      in total, followed by landslide (19.7%) and structural collapse (10.1%). However,
      the causes of deaths differed between disaster types. The meteorological disaster
      associated with the greatest number of deaths has changed from flood to typhoon.
      Factors that raised vulnerability included living in coastal provinces (11.3
      times higher than inland metropolitan), male gender (1.9 times higher than
      female), and older age. CONCLUSIONS: Epidemiological analyses of the causes of
      death and vulnerability associated with meteorological disasters can provide the
      necessary information for establishing future adaptation measures against climate
      change. A more comprehensive system for assessing disaster epidemiology needs to
      be established.

PMID- 21943039
TI  - Magnetic resonance imaging is an accurate and reliable method to evaluate non
      cystic fibrosis paediatric lung disease.
AB  - BACKGROUND AND OBJECTIVE: Chest MRI is increasingly used to assess pulmonary
      diseases, but its utility compared with high-resolution computed tomography
      (HRCT) has never been evaluated in children using specific performance outcomes.
      The aim of this study was to assess the accuracy and reliability of MRI compared
      with HRCT in children with non-cystic fibrosis (CF) chronic lung disease.
      METHODS: Fifty subjects aged 5.9-20 years, with primary ciliary dyskinesia (n =
      17), primary immunodeficiency (n = 17) or recurrent pneumonia (n = 16), underwent
      chest HRCT and MRI. The prevalence of lung abnormalities on HRCT was evaluated,
      and sensitivity, specificity, accuracy and positive and negative likelihood
      ratios for MRI versus HRCT were calculated. MRI and HRCT scans were also assessed
      using a modified Helbich score. RESULTS: Bronchiectasis, mucous plugging,
      peribronchial wall thickening, consolidation, bullae, abscesses and emphysema
      were detected by HRCT in 72, 68, 66, 60, 10, 8 and 8% of subjects, respectively.
      Sensitivity, specificity, accuracy and positive and negative likelihood ratios
      for MRI were good or excellent for most of the changes that were assessed. Median
      total Helbich scores for HRCT and MRI were 10 (range 0-20) and 10 (range 0-18),
      respectively. There was good-to-excellent agreement between the two techniques
      for all scores (r >= 0.8). A Bland-Altman plot confirmed this agreement between
      total scores (bias value: 0.2 +/- 1.18; 95% limits of agreement of mean
      difference: -2.12-2.52). CONCLUSIONS: Chest MRI was equivalent to HRCT to
      determine the extent of lung disease in children with non-CF lung disease. The
      findings support the use of chest MRI as an alternative to HRCT in diagnostic
      pathways for paediatric chronic lung disorders.

PMID- 21943040
TI  - Discordant lymphoma consisting of splenic mantle cell lymphoma and marginal zone
      lymphoma involving the bone marrow and peripheral blood: a case report.
AB  - INTRODUCTION: Discordant lymphomas are rare entities characterized by the
      simultaneous presence of two distinct types of lymphomas in different anatomic
      sites. We describe a very rare case of simultaneous occurrence of splenic mantle
      cell lymphoma and marginal zone lymphoma involving the bone marrow and peripheral
      blood. CASE PRESENTATION: We report the case of a 60-year-old asymptomatic
      Caucasian woman in whom discordant lymphomas were discovered when a slight
      lymphocytosis and a conspicuous splenomegaly were observed. The different
      morphological, immunophenotypical and immunohistochemical features found in the
      different pathologic samples obtained from peripheral blood, bone marrow and
      spleen sections made it possible to differentiate two types of non-Hodgkin B-cell
      lymphomas: a mantle cell lymphoma infiltrating the spleen and a marginal zone
      lymphoma involving both the bone marrow and peripheral blood. Since a similar IgH
      gene rearrangement was found both in the bone marrow and in the spleen, the
      hypothesis of a common origin, followed by a different clonal selection of the
      neoplastic lymphocytes may be taken into consideration. CONCLUSION: Our case
      emphasizes the usefulness of investigating simultaneous specimens from different
      anatomic sites from the same patient and the relevant diagnostic role of
      splenectomy.

PMID- 21943041
TI  - Change in bias in self-reported body mass index in Australia between 1995 and
      2008 and the evaluation of correction equations.
AB  - BACKGROUND: Many studies have documented the bias in body mass index (BMI)
      determined from self-reported data on height and weight, but few have examined
      the change in bias over time. METHODS: Using data from large, nationally
      representative population health surveys, we examined change in bias in height
      and weight reporting among Australian adults between 1995 and 2008. Our study
      dataset included 9,635 men and women in 1995 and 9,141 in 2007-2008. We
      investigated the determinants of the bias and derived correction equations using
      2007-2008 data, which can be applied when only self-reported anthropometric data
      are available. RESULTS: In 1995, self-reported BMI (derived from height and
      weight) was 1.2 units (men) and 1.4 units (women) lower than measured BMI. In
      2007-2008, there was still underreporting, but the amount had declined to 0.6
      units (men) and 0.7 units (women) below measured BMI. The major determinants of
      reporting error in 2007-2008 were age, sex, measured BMI, and education of the
      respondent. Correction equations for height and weight derived from 2007-2008
      data and applied to self-reported data were able to adjust for the bias and were
      accurate across all age and sex strata. CONCLUSIONS: The diminishing reporting
      bias in BMI in Australia means that correction equations derived from 2007-2008
      data may not be transferable to earlier self-reported data. Second, predictions
      of future overweight and obesity in Australia based on trends in self-reported
      information are likely to be inaccurate, as the change in reporting bias will
      affect the apparent increase in self-reported obesity prevalence.

PMID- 21943042
TI  - The relationship between job satisfaction, burnout, and turnover intention among
      physicians from urban state-owned medical institutions in Hubei, China: a cross
      sectional study.
AB  - BACKGROUND: Throughout China, a growing number of physicians are leaving or
      intending to depart from their organizations owing to job dissatisfaction. Little
      information is available about the role of occupational burnout in this
      association. We set out to analyze the relationship between job satisfaction,
      burnout, and turnover intention, and further to determine whether occupational
      burnout can serve as a mediator among Chinese physicians from urban state-owned
      medical institutions. METHODS: A cross-sectional survey was carried out in March
      2010 in Hubei Province, central China. The questionnaires assessed
      sociodemographic characteristics, job satisfaction, burnout, and turnover
      intention. The job satisfaction and occupational burnout instruments were
      obtained by modifying the Chinese Physicians' Job Satisfaction Questionnaire
      (CPJSQ) and the Chinese Maslach Burnout Inventory (CMBI), respectively. Such
      statistical methods as one-way ANOVA, Pearson correlation, GLM-univariate and
      structural equation modeling were used. RESULTS: Of the 1600 physicians surveyed,
      1451 provided valid responses. The respondents had medium scores (3.18 +/-0.73)
      on turnover intention, in which there was significant difference among the groups
      from three urban areas with different development levels. Turnover intention,
      which significantly and negatively related to all job-satisfaction subscales,
      positively related to each subscale of burnout syndrome. Work environment
      satisfaction (b = -0.074, p < 0.01), job rewards satisfaction (b = -0.073, p <
      0.01), organizational management satisfaction (b = -0.146, p < 0.01), and
      emotional exhaustion (b = 0.135, p < 0.01) were identified as significant direct
      predictors of the turnover intention of physicians, with 41.2% of the variance
      explained unitedly, under the control of sociodemographic variables, among which
      gender, age, and years of service were always significant. However, job-itself
      satisfaction no longer became significant, with the estimated parameter on job
      rewards satisfaction smaller after burnout syndrome variables were included. As
      congregated latent concepts, job satisfaction had both significant direct effects
      (gamma21 = -0.32, p < 0.01) and indirect effects (gamma11 * beta21 = -0.13, p <
      0.01) through occupational burnout (62% explained) as a mediator on turnover
      intention (47% explained). CONCLUSIONS: Our study reveals that several, but not
      all dimensions of both job satisfaction and burnout syndrome are relevant factors
      affecting physicians' turnover intention, and there may be partial mediation
      effects of occupational burnout, mainly through emotional exhaustion, within the
      impact of job satisfaction on turnover intention. This suggests that enhancements
      in job satisfaction can be expected to reduce physicians' intentions to quit by
      the intermediary role of burnout as well as the direct path. It is hoped that
      these findings will offer some clues for health-sector managers to keep their
      physician resource motivated and stable.

PMID- 21943043
TI  - Mobilisation and remobilisation of a large archetypal pathogenicity island of
      uropathogenic Escherichia coli in vitro support the role of conjugation for
      horizontal transfer of genomic islands.
AB  - BACKGROUND: A substantial amount of data has been accumulated supporting the
      important role of genomic islands (GEIs)--including pathogenicity islands (PAIs)-
      in bacterial genome plasticity and the evolution of bacterial pathogens. Their
      instability and the high level sequence similarity of different (partial) islands
      suggest an exchange of PAIs between strains of the same or even different
      bacterial species by horizontal gene transfer (HGT). Transfer events of
      archetypal large genomic islands of enterobacteria which often lack genes
      required for mobilisation or transfer have been rarely investigated so far.
      RESULTS: To study mobilisation of such large genomic regions in prototypic
      uropathogenic E. coli (UPEC) strain 536, PAI II536 was supplemented with the
      mobRP4 region, an origin of replication (oriVR6K), an origin of transfer
      (oriTRP4) and a chloramphenicol resistance selection marker. In the presence of
      helper plasmid RP4, conjugative transfer of the 107-kb PAI II536 construct
      occured from strain 536 into an E. coli K-12 recipient. In transconjugants, PAI
      II536 existed either as a cytoplasmic circular intermediate (CI) or integrated
      site-specifically into the recipient's chromosome at the leuX tRNA gene. This
      locus is the chromosomal integration site of PAI II536 in UPEC strain 536. From
      the E. coli K-12 recipient, the chromosomal PAI II536 construct as well as the
      CIs could be successfully remobilised and inserted into leuX in a PAI II536
      deletion mutant of E. coli 536. CONCLUSIONS: Our results corroborate that
      mobilisation and conjugal transfer may contribute to evolution of bacterial
      pathogens through horizontal transfer of large chromosomal regions such as PAIs.
      Stabilisation of these mobile genetic elements in the bacterial chromosome result
      from selective loss of mobilisation and transfer functions of genomic islands.

PMID- 21943044
TI  - The effect of participatory women's groups on birth outcomes in Bangladesh: does
      coverage matter? Study protocol for a randomized controlled trial.
AB  - BACKGROUND: Progress on neonatal survival has been slow in most countries. While
      there is evidence on what works to reduce newborn mortality, there is limited
      knowledge on how to deliver interventions effectively when health systems are
      weak. Cluster randomized trials have shown strong reductions in neonatal
      mortality using community mobilisation with women's groups in rural Nepal and
      India. A similar trial in Bangladesh showed no impact. A main hypothesis is that
      this negative finding is due to the much lower coverage of women's groups in the
      intervention population in Bangladesh compared to India and Nepal. For evidence
      based policy making it is important to examine if women's group coverage is a
      main determinant of their impact. The study aims to test the effect on newborn
      and maternal health outcomes of a participatory women's group intervention with a
      high population coverage of women's groups. METHODS: A cluster randomised trial
      of a participatory women's group intervention will be conducted in 3 districts of
      rural Bangladesh. As we aim to study a women's group intervention with high
      population coverage, the same 9 intervention and 9 control unions will be used as
      in the 2005-2007 trial. These had been randomly allocated using the districts as
      strata. To increase coverage, 648 new groups were formed in addition to the 162
      existing groups that were part of the previous trial. An open cohort of women who
      are permanent residents in the union in which their delivery or death was
      identified, is enrolled. Women and their newborns are included after birth, or,
      if a woman dies during pregnancy, after her death. Excluded are women who are
      temporary residents in the union in which their birth or death was identified.
      The primary outcome is neonatal mortality in the last 24 months of the study. A
      low cost surveillance system will be used to record all birth outcomes and deaths
      to women of reproductive age in the study population. Data on home care practices
      and health care use are collected through interviews. TRIAL REGISTRATION: ISRCTN:
      ISRCTN01805825.

PMID- 21943045
TI  - A comparison of cryopreservation methods: Slow-cooling vs. rapid-cooling based on
      cell viability, oxidative stress, apoptosis, and CD34+ enumeration of human
      umbilical cord blood mononucleated cells.
AB  - BACKGROUND: The finding of human umbilical cord blood as one of the most likely
      sources of hematopoietic stem cells offers a less invasive alternative for the
      need of hematopoietic stem cell transplantation. Due to the once-in-a-life time
      chance of collecting it, an optimum cryopreservation method that can preserve the
      life and function of the cells contained is critically needed. METHODS: Until
      now, slow-cooling has been the routine method of cryopreservation; however, rapid
      cooling offers a simple, efficient, and harmless method for preserving the life
      and function of the desired cells. Therefore, this study was conducted to compare
      the effectiveness of slow- and rapid-cooling to preserve umbilical cord blood of
      mononucleated cells suspected of containing hematopoietic stem cells. The
      parameters used in this study were differences in cell viability, malondialdehyde
      content, and apoptosis level. The identification of hematopoietic stem cells
      themselves was carried out by enumerating CD34+ in a flow cytometer. RESULTS: Our
      results showed that mononucleated cell viability after rapid-cooling (91.9%) was
      significantly higher than that after slow-cooling (75.5%), with a p value =
      0.003. Interestingly, the malondialdehyde level in the mononucleated cell
      population after rapid-cooling (56.45 MUM) was also significantly higher than
      that after slow-cooling (33.25 MUM), with a p value < 0.001. The apoptosis level
      in rapid-cooling population (5.18%) was not significantly different from that of
      the mononucleated cell population that underwent slow-cooling (3.81%), with a p
      value = 0.138. However, CD34+ enumeration was much higher in the population that
      underwent slow-cooling (23.32 cell/MUl) than in the one that underwent rapid
      cooling (2.47 cell/MUl), with a p value = 0.001. CONCLUSIONS: Rapid-cooling is a
      potential cryopreservation method to be used to preserve the umbilical cord blood
      of mononucleated cells, although further optimization of the number of CD34+
      cells after rapid-cooling is critically needed.

PMID- 21943046
TI  - Use of allele-specific sequencing primers is an efficient alternative to PCR
      subcloning of low-copy nuclear genes.
AB  - Direct Sanger sequencing of polymerase chain reaction (PCR)-amplified nuclear
      genes leads to polymorphic sequences when allelic variation is present. To
      overcome this problem, most researchers subclone the PCR products to separate
      alleles. An alternative is to directly sequence the separate alleles using allele
      specific primers. We tested two methods to enhance the specificity of allele
      specific primers for use in direct sequencing: using short primers and
      amplification refractory mutation system (ARMS) technique. By shortening the
      allele-specific primer to 15-13 nucleotides, the single mismatch in the ultimate
      base of the primer is enough to hinder the amplification of the nontarget allele
      in direct sequencing and recover only the targeted allele at high accuracy. The
      deliberate addition of a second mismatch, as implemented in the ARMS technique,
      was less successful and seems better suited for allele-specific amplification in
      regular PCR rather than in direct sequencing.

PMID- 21943047
TI  - Socially tuned: brain responses differentiating human and animal motion.
AB  - Typical adult observers demonstrate enhanced behavioral sensitivity to human
      movement compared to animal movement. Yet, the neural underpinnings of this
      effect are unknown. We examined the tuning of brain mechanisms for the perception
      of biological motion to the social relevance of this category of motion by
      comparing neural response to human and non-human biological motion. In
      particular, we tested the hypothesis that the response of the right posterior
      superior temporal sulcus (pSTS) varies according to the social relevance of the
      motion, responding most strongly to those biological motions with the greatest
      social relevance (human > dog). During a functional magnetic resonance imaging
      (fMRI) session, typical adults viewed veridical point-light displays of human,
      dog, and tractor motions created from motion capture data. A conjunction analysis
      identified regions of significant activation during biological motion perception
      relative to object motion. Within each of these regions, only one brain area, the
      right pSTS, revealed an enhanced response to human motion relative to dog motion.
      This finding demonstrates that the pSTS response is sensitive to the social
      relevance of a biological motion stimulus. 

PMID- 21943048
TI  - Genomic, RNA, and ecological divergences of the Revolver transposon-like multi
      gene family in Triticeae.
AB  - BACKGROUND: Revolver is a newly discovered multi-gene family of transposable
      elements in the Triticeae genome. Revolver encompasses 2929 to 3041 bp, has 20 bp
      of terminal inverted repeated sequences at both ends, and contains a
      transcriptionally active gene encoding a DNA-binding-like protein. A putative
      TATA box is located at base 221, with a cap site at base 261 and a possible
      polyadenylation signal AATAAA at base 2918. Revolver shows considerable
      quantitative variation in wheat and its relatives. RESULTS: Revolver cDNAs varied
      between 395 and 2,182 bp in length. The first exon exhibited length variation,
      but the second and third exons were almost identical. These variants in the
      Revolver family shared the downstream region of the second intron, but varied
      structurally at the 5' first exon. There were 58 clones, which showed partial
      homology to Revolver, among 440,000 expressed sequence tagged (EST) clones
      sourced from Triticeae. In these Revolver homologues with lengths of 360-744 bp,
      the portion after the 2nd exon was conserved (65-79% homology), but the 1st exon
      sequences had mutually low homology, with mutations classified into 12 types, and
      did not have EST sequences with open reading frames (ORFs). By PCR with the 3'
      flanking region of a typical genomic clone of Revolver-2 used as a single primer,
      rye chromosomes 1R and 5R could be simultaneously identified. Extensive eco
      geographic diversity and divergence was observed among 161 genotypes of the
      single species Triticum dicoccoides collected from 18 populations in Israel with
      varying exposures to abiotic and biotic stresses (soil, temperature, altitude,
      water availability, and pathogens). CONCLUSIONS: On the base of existing
      differences between Revolver variants, the molecular markers that can distinguish
      different rye chromosomes were developed. Eco-geographic diversification of wild
      emmer T. dicoccoides in Israel and high Revolver copy numbers are associated with
      higher rainfall and biotic stresses. The remarkable quantitative differences
      among copy numbers of Revolver in the same species from different ecosystems
      suggest strong amplification activity within the last 10,000 years. It is the
      interesting finding because the majority of Triticeae high-copy transposable
      elements seem to be inactive at the recent time except for BARE-1 element in
      Hordeum and the fact might be interesting to perceive the processes of plant
      adaptive evolution.

PMID- 21943050
TI  - HPV infection among rural American Indian women and urban white women in South
      Dakota: an HPV prevalence study.
AB  - BACKGROUND: High-risk strains of human papillomavirus (HPV) cause cervical
      cancer. American Indian (AI) women in the Northern Plains of the U.S. have
      significantly higher incidence and mortality rates for cervical cancer than White
      women in the same geographical area. We compared HPV prevalence, patterns of HPV
      types, and infection with multiple HPV types in AI and White women living in
      South Dakota, U.S. METHODS: We analyzed the HPV status of cervical samples
      collected in 2006-2008 from women aged 18-65 years who attended two rural AI
      reservation clinics (n = 235) or an urban clinic in the same area serving mostly
      White women (n = 246). Data collection occurred before HPV vaccination was
      available to study participants. HPV DNA was amplified by using the L1 consensus
      primer system and an HPV Linear Array detection assay to identify HPV types. We
      used chi-square tests to compare HPV variables, with percentages standardized by
      age and lifetime number of sexual partners. RESULTS: Compared to White women, AI
      women were younger (p = 0.01) and reported more sexual partners (p < 0.001). A
      lower percentage of AI women tested negative for HPV infection compared to Whites
      (58% [95% CI = 51-65] vs. 77% [95% CI = 71-82]; p < 0.001), and a higher
      percentage of AI women were infected by oncogenic types (30% [95% CI = 25-36] vs.
      16% [95% CI = 11-21]; p = 0.001). Infections among AI women showed a wider
      variety and very different pattern of HPV types, including a higher prevalence of
      mixed HPV infections (19% [95% CI = 26-38] vs. 7% [95% CI = 4-11]; p = 0.001). AI
      women had a higher percentage of HPV infections that were not preventable by HPV
      vaccination (32% [95% CI = 26-38] vs. 15% [95% CI = 11-21]; p < 0.001).
      CONCLUSIONS: A higher HPV burden and a different HPV genotyping profile may
      contribute to the high rate of cervical cancer among AI women.

PMID- 21943049
TI  - Dupuytren's: a systems biology disease.
AB  - Dupuytren's disease (DD) is an ill-defined fibroproliferative disorder of the
      palm of the hands leading to digital contracture. DD commonly occurs in
      individuals of northern European extraction. Cellular components and processes
      associated with DD pathogenesis include altered gene and protein expression of
      cytokines, growth factors, adhesion molecules, and extracellular matrix
      components. Histology has shown increased but varying levels of particular types
      of collagen, myofibroblasts and myoglobin proteins in DD tissue. Free radicals
      and localised ischaemia have been suggested to trigger the proliferation of DD
      tissue. Although the existing available biological information on DD may contain
      potentially valuable (though largely uninterpreted) information, the precise
      aetiology of DD remains unknown. Systems biology combines mechanistic modelling
      with quantitative experimentation in studies of networks and better understanding
      of the interaction of multiple components in disease processes. Adopting systems
      biology may be the ideal approach for future research in order to improve
      understanding of complex diseases of multifactorial origin. In this review, we
      propose that DD is a disease of several networks rather than of a single gene,
      and show that this accounts for the experimental observations obtained to date
      from a variety of sources. We outline how DD may be investigated more effectively
      by employing a systems biology approach that considers the disease network as a
      whole rather than focusing on any specific single molecule.

PMID- 21943051
TI  - Evaluation of clinical endobronchial ultrasound skills following clinical versus
      simulation training.
AB  - BACKGROUND AND OBJECTIVE: Endobronchial ultrasound with transbronchial needle
      aspiration (EBUS-TBNA) is a pulmonary procedure that can be challenging to learn.
      This study aims to compare trainee EBUS-TBNA performance during clinical
      procedures, following training with a computer EBUS-TBNA simulator versus
      conventional clinical EBUS-TBNA training. METHODS: A prospective study of
      pulmonary trainees performing EBUS-TBNA procedures on patients with suspected
      lung cancer and mediastinal adenopathy. Two cohorts of trainees were each
      evaluated while performing EBUS-TBNA on two patients. Group 1 received training
      by performing 15 cases on an EBUS-TBNA simulator (n = 4) and had never performed
      a clinical EBUS-TBNA procedure. Group 2 received training by doing 15-25 EBUS
      TBNA procedures on patients (n = 4). RESULTS: There was no significant difference
      in the primary outcome measure of total EBUS-TBNA procedure time/number of
      successful aspirates between Groups 1 and 2 (3.95 (+/-0.93) vs 3.64 (+/-0.89), P
      = 0.51). Total learner EBUS-TBNA procedure time in minutes (23.67 (+/-5.58) vs
      21.81 (+/-5.36), P = 0.17) and percentage of successful aspirates (93.3% (+/
      5.8%) vs 86.3% (+/-6.7%), P = 0.12) were not significantly different between
      Group 1 and Group 2. The only significant difference found between Group 1 and
      Group 2 was time to intubation in minutes (0.99 (+/-0.46) vs 0.50 (+/-0.42), P =
      0.04). CONCLUSIONS: EBUS-TBNA simulator use leads to rapid acquisition of
      clinical EBUS-TBNA skills comparable with that obtained with conventional
      training methods using practice on patients, suggesting that skills learned using
      an EBUS-TBNA simulator are transferable to clinical EBUS-TBNA performance. EBUS
      TBNA simulators show promise for training, potentially minimizing the burden of
      procedural learning on patients.

PMID- 21943052
TI  - Maternal left ventricular and endothelial functions in preeclampsia.
AB  - OBJECTIVE: To compare maternal left ventricular and endothelial functions in
      preeclampsia and normal pregnancy, during pregnancy and after delivery. DESIGN:
      Observational study with follow-up. SETTING: University hospital and midwife-led
      antenatal care center. SAMPLES: Twenty untreated women with preeclampsia and 20
      women with normal pregnancy, matched for gestational age and parity. METHODS: The
      women were examined during pregnancy and three months after delivery. Left
      ventricular function was assessed by echocardiography, including tissue-Doppler
      imaging. Endothelial function was assessed by measuring flow-mediated dilation of
      the brachial artery. MAIN OUTCOME MEASURES: Early diastolic mitral annular tissue
      velocity, "e", peak systolic tissue velocity, "S", and flow-mediated dilation.
      RESULTS: The diastolic function was reduced in preeclampsia, with lower "e", and
      there was a higher ratio of early diastolic mitral inflow velocity and early
      diastolic mitral annular velocity, "E/e". Early diastolic mitral inflow
      deceleration time and isovolumetric relaxation time were similar between the
      groups, suggesting pseudonormalization and increased filling pressures in
      preeclampsia. "S" was lower in the preeclampsia group during pregnancy. Both
      diastolic and systolic left ventricular functions normalized postpartum. The flow
      mediated dilation was impaired in the preeclampsia group both during pregnancy
      and three months after delivery. CONCLUSIONS: The maternal left ventricular
      function was impaired during preeclampsia but had normalized three months after
      delivery. The endothelial function, measured by flow-mediated dilation, was
      impaired in the preeclampsia group as compared with the normal pregnancy group
      both during pregnancy and three months after delivery.

PMID- 21943053
TI  - Complex regional pain syndrome with associated chest wall dystonia: a case
      report.
AB  - Patients with complex regional pain syndrome (CRPS) often suffer from an array
      of associated movement disorders, including dystonia of an affected limb. We
      present a case of a patient with long standing CRPS after a brachial plexus
      injury, who after displaying several features of the movement disorder
      previously, developed painful dystonia of chest wall musculature. Detailed
      neurologic examination found palpable sustained contractions of the pectoral and
      intercostal muscles in addition to surface allodynia. Needle electromyography of
      the intercostal and paraspinal muscles supported the diagnosis of dystonia. In
      addition, pulmonary function testing showed both restrictive and obstructive
      features in the absence of a clear cardiopulmonary etiology. Treatment was
      initiated with intrathecal baclofen and the patient had symptomatic relief and
      improvement of dystonia. This case illustrates a novel form of the movement
      disorder associated with CRPS with response to intrathecal baclofen treatment.

PMID- 21943054
TI  - Semiallogenic fusions of MSI(+) tumor cells and activated B cells induce MSI
      specific T cell responses.
AB  - BACKGROUND: Various strategies have been developed to transfer tumor-specific
      antigens into antigen presenting cells in order to induce cytotoxic T cell
      responses against tumor cells. One approach uses cellular vaccines based on
      fusions of autologous antigen presenting cells and allogeneic tumor cells. The
      fusion cells combine antigenicity of the tumor cell with optimal
      immunostimulatory capacity of the antigen presenting cells.Microsatellite
      instability caused by mutational inactivation of DNA mismatch repair genes
      results in translational frameshifts when affecting coding regions. It has been
      shown by us and others that these mutant proteins lead to the presentation of
      immunogenic frameshift peptides that are - in principle - recognized by a
      multiplicity of effector T cells. METHODS: We chose microsatellite instability
      induced frameshift antigens as ideal to test for induction of tumor specific T
      cell responses by semiallogenic fusions of microsatellite instable carcinoma
      cells with CD40-activated B cells. Two fusion clones of HCT116 with activated B
      cells were selected for stimulation of T cells autologous to the B cell fusion
      partner. Outgrowing T cells were phenotyped and tested in functional assays.
      RESULTS: The fusion clones expressed frameshift antigens as well as high amounts
      of MHC and costimulatory molecules. Autologous T cells stimulated with these
      fusions were predominantly CD4(+), activated, and reacted specifically against
      the fusion clones and also against the tumor cell fusion partner. Interestingly,
      a response toward 6 frameshift-derived peptides (of 14 tested) could be observed.
      CONCLUSION: Cellular fusions of MSI(+) carcinoma cells and activated B cells
      combine the antigen-presenting capacity of the B cell with the antigenic
      repertoire of the carcinoma cell. They present frameshift-derived peptides and
      can induce specific and fully functional T cells recognizing not only fusion
      cells but also the carcinoma cells. These hybrid cells may have great potential
      for cellular immunotherapy and this approach should be further analyzed in
      preclinical as well as clinical trials. Moreover, this is the first report on the
      induction of frameshift-specific T cell responses without the use of synthetic
      peptides.

PMID- 21943055
TI  - Patterns of amino acid metabolism by proliferating human mesenchymal stem cells.
AB  - The nutritional requirements of stem cells have not been determined; in
      particular, the amino acid metabolism of stem cells is largely unknown. In this
      study, we investigated the amino acid metabolism of human mesenchymal stem cells
      (hMSCs), with focus on two questions: Which amino acids are consumed and/or
      secreted by hMSCs and at what rates? To answer these questions, hMSCs were
      cultured on tissue culture plastic and in a bioreactor, and their amino acid
      profile was analyzed. The results showed that the kinetics of hMSCs growth and
      amino acid metabolism were significantly higher for hMSCs in tissue culture
      plastic than in the bioreactor. Despite differences in culture conditions, 8
      essential and 6 nonessential amino acids were consumed by hMSCs in both tissue
      culture plastic and bioreactor cultures. Glutamine was the most consumed amino
      acid with significantly higher rates than for any other amino acid. The
      metabolism of nonessential amino acids by hMSCs deviated significantly from that
      of other cell lines. The secretion of alanine, glycine, glutamate, and ornithine
      by hMSCs showed that there is a strong overflow metabolism that can be due to the
      high concentrations of amino acids provided in the medium. In addition, the data
      showed that there is a metabolic pattern for proliferating hMSCs, which can
      contribute to the design of medium without animal serum for stem cells. Further,
      this study shows how to implement amino acid rates and metabolic principles in
      three-dimensional stem cell biology.

PMID- 21943057
TI  - Alterations of serum biomarkers associated with lung ventilation function
      impairment in coal workers: a cross-sectional study.
AB  - BACKGROUND: Previous studies have demonstrated that alterations in certain
      circulating biomarkers may be correlated with Coal workers' pneumoconiosis (CWP).
      This study investigated the relationship between changes of serum biomarkers and
      pulmonary function during the development of CWP. METHODS: Lung function
      parameters and specific serum indices were measured in 69 non-smoking coal
      workers, including 34 miners with CWP, 24 asymptomatic miners and 11 miners with
      minimal symptoms. The associations between changes in pulmonary function and
      serum indices were tested with Pearson's correlation coefficients. Multivariable
      analysis was used to estimate the predictive power of potential determinant
      variables for lung function. RESULTS: Compared to healthy miners, lung function
      (FVC, FEV1, FEF50, FEF75, FEF25-75 % of predicted values) was decreased in miners
      with CWP (p < 0.05). Increased serum matrix metalloproteinase-9 (MMP-9) was
      associated with decreased FVC% of predicted values in the asymptomatic miners (r
      = -0.503, p = 0.014). CONCLUSIONS: In coal mine workers, alterations of lung
      function parameters are associated with the development of CWP and with changes
      in circulating MMP-9, TIMP-9, IL-13 and IL-18R. These serum biomarkers may likely
      reflect the pathogenesis and progression of CWP in coal workers, and may provide
      for the importance of serum indicators in the early diagnosis of lung function
      injury in coal miners.

PMID- 21943056
TI  - Improved vaccine protection against retrovirus infection after co-administration
      of adenoviral vectors encoding viral antigens and type I interferon subtypes.
AB  - BACKGROUND: Type I interferons (IFNs) exhibit direct antiviral effects, but also
      distinct immunomodulatory properties. In this study, we analyzed type I IFN
      subtypes for their effect on prophylactic adenovirus-based anti-retroviral
      vaccination of mice against Friend retrovirus (FV) or HIV. RESULTS: Mice were
      vaccinated with adenoviral vectors encoding FV Env and Gag proteins alone or in
      combination with vectors encoding IFNalpha1, IFNalpha2, IFNalpha4, IFNalpha5,
      IFNalpha6, IFNalpha9 or IFNbeta. Only the co-administration of adenoviral vectors
      encoding IFNalpha2, IFNalpha4, IFNalpha6 and IFNalpha9 resulted in strongly
      improved immune protection of vaccinated mice from subsequent FV challenge
      infection with high control over FV-induced splenomegaly and reduced viral loads.
      The level of protection correlated with augmented virus-specific CD4(+) T cell
      responses and enhanced antibody titers. Similar results were obtained when mice
      were vaccinated against HIV with adenoviral vectors encoding HIV Env and Gag-Pol
      in combination with various type I IFN encoding vectors. Here mainly CD4(+) T
      cell responses were enhanced by IFNalpha subtypes. CONCLUSIONS: Our results
      indicate that certain IFNalpha subtypes have the potential to improve the
      protective effect of adenovirus-based vaccines against retroviruses. This
      correlated with augmented virus-specific CD4(+) T cell and antibody responses.
      Thus, co-expression of select type I IFNs may be a valuable tool for the
      development of anti-retroviral vaccines.

PMID- 21943059
TI  - Osteonecrosis of the jaw as a possible rare side effect of annual bisphosphonate
      administration for osteoporosis: A case report.
AB  - INTRODUCTION: Osteonecrosis of the jaw is a serious side effect in patients
      receiving nitrogen-containing bisphosphonates intravenously due to malignant
      diseases. Albeit far less frequently, osteonecrosis of the jaw has also been
      reported to occur due to the oral administration of nitrogen-containing
      bisphosphonates due to osteoporosis. Annual infusions of zoledronic acid have
      been recommended in order to improve patient compliance, to optimize therapeutic
      effects and to minimize side effects. To date, osteonecrosis of the jaw has not
      been linked to the annual administration of bisphosphonates. CASE PRESENTATION:
      We report the case of a 65-year-old Caucasian woman suffering from osteoporosis
      who developed early stage osteonecrosis of the jaw in two locations, with chronic
      infections, after two months of oral bisphosphonate treatment and three annual
      administrations of zoledronic acid. Our patient was treated by fluorescence
      guided resection of the necrotic jaw bone areas; local inflammation was treated
      by removal of a wisdom tooth and repeat root resections. Histopathology revealed
      typical hallmarks of osteonecrosis of the jaw. CONCLUSION: Osteonecrosis of the
      jaw may occur as a consequence of annual administrations of zoledronic acid. It
      is conceivable that, due to the pharmacological properties of bisphosphonates, a
      jaw bone that encounters frequent local inflammations is more likely to develop
      osteonecrosis.

PMID- 21943058
TI  - Why the increase in under five mortality in Uganda from 1995 to 2000? A
      retrospective analysis.
AB  - BACKGROUND: From 1995-2000 the under five mortality rate in Uganda increased from
      147.3 to 151.5 deaths per 1000 live births and reasons for the increase were not
      clear. This study was undertaken to understand factors influencing the increase
      in under five mortality rate during 1995-2000 in Uganda with a view of suggesting
      remedial actions. METHODS: We performed a comparative retrospective analysis of
      data derived from the 1995 and the 2000 Uganda demographic and health surveys. We
      correlated the change of under five mortality rate in Uganda desegregated by
      region (central, eastern, north and western) with change in major known
      determinants of under five mortality such social economic circumstances, maternal
      factors, access to health services, and level of nutrition. RESULTS: The increase
      in under five mortality rate only happened in western Uganda with the other 3
      regions of Uganda (eastern, northern and central) showing a decrease. The changes
      in U5MR could not be explained by changes in poverty, maternal conditions, level
      of nutrition, or in access to health and other social services and in the
      prevalence of HIV among women attending for ante-natal care. All these factors
      did not reach statistical significance (P > 0.05) using Pearson's correlation
      coefficient. CONCLUSION: In order to explain these findings, there is need to
      find something that happened in western Uganda (but not other parts of the
      country) during the period 1995-2000 and has the potential to change the under
      five mortality by a big margin. We hypothesize that the increase in under five
      mortality could be explained by the severe malaria epidemic that occurred in
      western Uganda (but not other regions) in 1997/98.

PMID- 21943060
TI  - The cost associated with administering risperidone long-acting injections in the
      Australian community.
AB  - BACKGROUND: Risperidone long-acting injection (LAI) is mostly administered twice
      weekly to people with schizophrenia by nurses at community mental health centres
      (CMHC) or through mobile outreach visits. This study estimates the cost of
      resource utilisation associated with the administration of risperidone LAI and
      the potential savings from substituting two-weekly injections with a longer
      interval product of therapeutic equivalence. METHODS: A survey of mental health
      staff overseeing the administration of risperidone LAI at 253 distinct Australian
      CMHCs was undertaken in November 2009. For the two-week period prior to the
      survey, respondents were asked questions on injection time (and related tasks)
      and, for mobile outreach visits, distance and time travelled as well as reduction
      in visits. Results were stratified by Australian Standard Geographical
      Classification (ASGC) region. Resource use was quantified and valued in
      Australian dollars. RESULTS: Results are derived from 74 CMHCs, representing
      approximately 26% of the national average risperidone LAI unit two-week sales.
      Stratified average injection time (including related tasks) for risperidone LAI
      ranged from 18-29 minutes, with a national average of 20.12 minutes. For mobile
      outreach visits, average distance per patient ranged from 19.4 to 55.5 km for One
      Staff Visits and 15.2 to 218.1 km for More Than One Staff Visits, and average
      time travelled ranged from 34.1 to 54.5 minutes for One Staff Visits and 29.2 to
      136.3 minutes for More Than One Staff visits. The upper range consistently
      reflected greater resource utilisation in rural areas compared to urban areas. If
      administration of risperidone LAI had not been required, 20% fewer mobile
      outreach visits would have occurred. CONCLUSIONS: The national average saving per
      two-weekly risperidone long-acting injection avoided is $75.14. In 2009 in
      Australia, this would have saved ~$11 million for injection administration costs
      alone if all patients taking two-weekly risperidone LAI had instead been treated
      with a therapeutically equivalent long-acting injectable antipsychotic requiring
      one less injection per month.

PMID- 21943062
TI  - Membrane insertion and assembly of epitope-tagged gp9 at the tip of the M13
      phage.
AB  - BACKGROUND: Filamentous M13 phage extrude from infected Escherichia coli with a
      tip structure composed of gp7 and gp9. This tip structure is extended by the
      assembly of the filament composed of the major coat protein gp8. Finally, gp3 and
      gp6 terminate the phage structure at the proximal end. Up to now, gp3 has been
      the primary tool for phage display technology. However, gp7, gp8 and gp9 could
      also be used for phage display and these phage particles should bind to two
      different or more surfaces when the modified coat proteins are combined.
      Therefore, we tested here if the amino-terminal end of gp9 can be modified and
      whether the modified portion is exposed and detectable on the M13 phage
      particles. RESULTS: The amino-terminal region of gp9 was modified by inserting
      short sequences that encode antigenic epitopes. We show here that the modified
      gp9 proteins correctly integrate into the membrane using the membrane insertase
      YidC exposing the modified epitope into the periplasm. The proteins are then
      efficiently assembled onto the phage particles. Also extensions up to 36 amino
      acid residues at the amino-terminal end of gp9 did not interfere with membrane
      integration and phage assembly. The exposure of the antigenic tags on the phage
      was visualised with immunogold labelling by electron microscopy and verified by
      dot blotting with antibodies to the tags. CONCLUSIONS: Our results suggest that
      gp9 at the phage tip is suitable for the phage display technology. The modified
      gp9 can be supplied in trans from a plasmid and fully complements M13 phage with
      an amber mutation in gene 9. The modified phage tip is very well accessible to
      antibodies.

PMID- 21943061
TI  - Tracking of TV and video gaming during childhood: Iowa Bone Development Study.
AB  - BACKGROUND: Tracking studies determine the stability and predictability of
      specific phenomena. This study examined tracking of TV viewing (TV) and video
      game use (VG) from middle childhood through early adolescence after adjusting for
      moderate and vigorous physical activity (MVPA), percentage of body fat (% BF),
      and maturity. METHODS: TV viewing and VG use were measured at ages 5, 8, 11, and
      13 (n = 434) via parental- and self-report. MVPA was measured using the
      Actigraph, % BF using dual-energy x-ray absorptiometry, and maturity via Mirwald
      predictive equations. Generalized Estimating Equations (GEE) were used to assess
      stability and logistic regression was used to predict children "at risk" for
      maintaining sedentary behaviors. Additional models examined tracking only in
      overfat children (boys >= 25% BF; girls >= 32% BF). Data were collected from 1998
      to 2007 and analyzed in 2010. RESULTS: The adjusted stability coefficients (GEE)
      for TV viewing were 0.35 (95% CI = 0.26, 0.44) for boys, 0.32 (0.23, 0.40) for
      girls, and 0.45 (0.27, 0.64) for overfat. For VG use, the adjusted stability
      coefficients were 0.14 (0.05, 0.24) for boys, 0.24 (0.10, 0.38) for girls, and
      0.29 (0.08, 0.50) for overfat. The adjusted odds ratios (OR) for TV viewing were
      3.2 (2.0, 5.2) for boys, 2.9 (1.9, 4.6) for girls, and 6.2 (2.2, 17.2) for
      overfat. For VG use, the OR were 1.8 (1.1, 3.1) for boys, 3.5 (2.1, 5.8) for
      girls, and 1.9 (0.6, 6.1) for overfat. CONCLUSIONS: TV viewing and VG use are
      moderately stable throughout childhood and predictive of later behavior. TV
      viewing appears to be more stable in younger children than VG use and more
      predictive of later behavior. Since habitual patterns of sedentarism in young
      children tend to continue to adolescence, early intervention strategies,
      particularly to reduce TV viewing, are warranted.

PMID- 21943064
TI  - The impact of one night of sleep deprivation on moral judgments.
AB  - Recent studies have shown the existence of a relationship between sleep and moral
      judgment. In this study, we investigated whether one night of sleep deprivation
      affects the ability to judge the appropriateness of moral dilemmas. Forty-eight
      students had to judge 30 moral dilemmas at test, after a night of home sleep, and
      another 30 dilemmas at retest, following one night of continuous wakefulness. The
      60 dilemmas (20 moral impersonal, 20 moral personal, and 20 non-moral) were
      selected from Greene's dilemmas. Both groups judged the appropriateness of
      personal and impersonal dilemmas in the same way. A close to significant effect
      of sleep deprivation was observed on the reaction times for impersonal moral
      dilemmas, to which the deprived subjects responded faster (p = .05) than the
      control subjects. However, this was not the case for personal ones, for which no
      difference was significant. This result shows a greater ease/speed in responding
      to the (impersonal) dilemmas, which induce low emotional engagement after sleep
      deprivation, although the willingness to accept moral violations is not affected.
      This suggests that one night of sleep loss selectively influences the response
      speed only for moral impersonal dilemmas, probably due to disinhibition
      processes. The quality of moral judgment dilemmas does not seem to be easily
      influenced by a single night of sleep deprivation, but only by a longer lack of
      sleep. 

PMID- 21943063
TI  - Phytoestrogen consumption from foods and supplements and epithelial ovarian
      cancer risk: a population-based case control study.
AB  - BACKGROUND: While there is extensive literature evaluating the impact of
      phytoestrogen consumption on breast cancer risk, its role on ovarian cancer has
      received little attention. METHODS: We conducted a population-based case-control
      study to evaluate phytoestrogen intake from foods and supplements and epithelial
      ovarian cancer risk. Cases were identified in six counties in New Jersey through
      the New Jersey State Cancer Registry. Controls were identified by random digit
      dialing, CMS (Centers for Medicare and Medicaid Service) lists, and area
      sampling. A total of 205 cases and 390 controls were included in analyses.
      Unconditional logistic regression analyses were conducted to examine associations
      with total phytoestrogens, as well as isoflavones (daidzein, genistein,
      formononetin, and glycitein), lignans (matairesinol, lariciresinol, pinoresinol,
      secoisolariciresinol), and coumestrol. RESULTS: No statistically significant
      associations were found with any of the phytoestrogens under evaluation. However,
      there was a suggestion of an inverse association with total phytoestrogen
      consumption (from foods and supplements), with an odds ratio (OR) of 0.62 (95%
      CI: 0.38-1.00; p for trend: 0.04) for the highest vs. lowest tertile of
      consumption, after adjusting for reproductive covariates, age, race, education,
      BMI, and total energy. Further adjustment for smoking and physical activity
      attenuated risk estimates (OR: 0.66; 95% CI: 0.41-1.08). There was little
      evidence of an inverse association for isoflavones, lignans, or coumestrol.
      CONCLUSIONS: This study provided some suggestion that phytoestrogen consumption
      may decrease ovarian cancer risk, although results did not reach statistical
      significance.

PMID- 21943065
TI  - Chelex without boiling, a rapid and easy technique to obtain stable amplifiable
      DNA from small amounts of ethanol-stored spiders.
AB  - DNA barcoding projects require high-throughput generation of sequence data to
      assemble the comprehensive reference databases that are required to perform large
      scale biodiversity inventories and molecular ecology studies. With the advent of
      new sequencing technologies, the extraction step, which often requires a
      considerable amount of time and money, represents a significant bottleneck in
      many studies. Here, we present a one-step Chelex double-stranded DNA extraction
      protocol that is quick, cheap, easy and works with a small quantity of ethanol
      stored tissue. We developed this protocol by removing the denaturation step
      appearing in classic methods. This modification reduces the number of handling
      steps to one, thus simplifying the extraction procedure and reducing the risk of
      sample contamination, and yields double-stranded DNA instead of the single
      stranded form that classical Chelex extraction protocols usually release. DNA
      obtained through our method is then suitable for long-term conservation (over 1.5
      years). We tested our protocol on a highly diverse genus of spiders comprised of
      mainly very small species. We also apply the method to two other genera of
      spiders, one with average size species, the other one with giant species, to test
      the efficacy of the method with varying amounts of input tissue. We also discuss
      the advantages and limitations of this DNA extraction technique when working with
      arthropods.

PMID- 21943066
TI  - Clinical prediction rules for invasive candidiasis in the ICU: ready for prime
      time?
AB  - Invasive candidiasis is a major source of morbidity and mortality in critically
      ill patients. The creation and validation of clinical prediction rules to
      identify patients at high risk has given clinicians access to advanced management
      strategies, such as targeted prophylaxis, pre-emptive therapy, and protocolized
      empirical therapy.

PMID- 21943067
TI  - DIABRISK-SL prevention of cardio-metabolic disease with life style modification
      in young urban Sri Lankan's--study protocol for a randomized controlled trial.
AB  - BACKGROUND: Urban South-Asian's are predisposed to early onset of type 2 diabetes
      mellitus (T2DM) and cardiovascular disease (CVD). There is an urgent need for
      country specific primary prevention strategies to address the growing burden of
      cardio-metabolic disease in this population. The aim of this clinical trial is to
      evaluate whether intensive (3-monthly) lifestyle modification advice is superior
      to a less-intensive (12 monthly; control group) lifestyle modification advice on
      a primary composite cardio-metabolic end point in 'at risk' urban subjects aged
      between 5-40 years. METHODS/DESIGN: This is an open randomised controlled
      parallel group clinical trial performed at a single centre in Colombo, Sri-Lanka.
      A cluster sampling strategy was used to select a large representative sample of
      subjects aged between 5-40 years at high risk of T2DM and CVD for the
      intervention study. We have screened 23,298 (males 47% females 53%) healthy
      subjects for four risk factors: obesity, elevated waist circumference, family
      history of diabetes and physical inactivity, using a questionnaire and
      anthropometry. Those with two or more risk-factors were recruited to the
      intervention trial. We aim to recruit 4600 subjects for the intervention trial.
      The primary composite cardio-metabolic end point is; new onset T2DM, impaired
      glucose tolerance, impaired fasting glycaemia, new onset hypertension and
      albuminuria, following 5 years of intervention. The effect of the intervention on
      pre-specified secondary endpoints will also be evaluated. The study will be
      conducted according to good clinical and ethical practice, data analysis and
      reporting guidelines. DISCUSSION: DIABRISK-SL is a large population based trial
      to evaluate the prevalence of diabetes, pre-diabetes and cardio-metabolic risk
      factors among young urban Sri-Lankans and the effect of a primary prevention
      strategy on cardio-metabolic disease end points. This work will enable country
      specific and regional cardio-metabolic risk scores to be derived. Further if the
      proposed intervention is successful the results of this study can be translated
      and implemented as a low-cost primary prevention tool in Sri-Lanka and other
      low/middle income developing countries. TRIAL REGISTRATION: The trial is
      registered with the World Health Organisation and Sri-Lanka clinical trial
      registry number SLCTR/2008/003.

PMID- 21943068
TI  - Clinical response to Auron Misheil Therapy in a man with advanced multifocal
      hepatocellular carcinoma: A case report.
AB  - INTRODUCTION: Auron Misheil Therapy was developed based on similarities between
      carcinogenesis and inflammation. Auron Misheil Therapy is a combination of
      natural and synthetic compounds, including anti-inflammatory drugs and insulin,
      expected to exhibit synergistic effects. CASE PRESENTATION: Here, we report the
      case of a 78-year-old Caucasian male patient who presented with multifocal
      hepatocellular carcinoma and chronic hepatitis C virus infection. Over a four
      year period our patient was treated with radiofrequency ablation and
      transarterial chemoembolization. After these treatments there was tumor
      progression, with new hyperperfused lesions without evidence of extrahepatic
      tumor involvement. Our patient refused sorafenib therapy. Therefore, he received
      twice daily intramuscular injections of Auron Misheil Therapy on an outpatient
      basis for two months. Partial remission of the hepatic lesions was observed eight
      weeks after the start of treatment, and confirmed four weeks later.
      Unfortunately, at that time our patient refused therapy due to dizziness. During
      follow-up two target lesions remained stable, but one lesion increased in size.
      At the latest follow-up, one year later, there was still tumor control.
      CONCLUSION: While the mechanisms underlying the antitumor effects of Auron
      Misheil Therapy are not fully understood, stable disease and remissions have been
      observed in different types of tumors, including hepatocellular carcinoma.

PMID- 21943069
TI  - A NOD2 gene polymorphism is associated with the prevalence and severity of
      chronic obstructive pulmonary disease in a Japanese population.
AB  - BACKGROUND AND OBJECTIVE: Genetic background is thought to be one of the risk
      factors for development of COPD. Recently, it has been proposed that the innate
      immune system is involved in the pathophysiology of COPD. We hypothesized that
      polymorphisms in the nucleotide-binding and oligomerization domain (NOD)1 and
      NOD2 genes would be associated with the pathogenesis of COPD. In addition, the
      associations between these single nucleotide polymorphisms (SNPs) and phenotypes
      of COPD were analysed. METHODS: Japanese COPD patients (n = 228) and non-COPD
      smokers (n = 101) were recruited from the outpatient clinic at Kyoto University
      Hospital, Kyoto, Japan. At entry into the study, a blood sample was taken and a
      pulmonary function test was performed. Genotyping was performed for 6 selected
      tag SNPs of NOD1 and 5 tag SNPs of NOD2. Further investigations were performed
      for SNP that were associated with COPD, including baseline gene expression, the
      relative proportions of splicing variants in whole blood, responses to ligand and
      enhancement of gene expression in peripheral blood neutrophils stimulated with
      pro-inflammatory cytokines. RESULTS: The distribution of NOD2 rs1077861 genotypes
      differed between Japanese COPD patients and non-COPD smokers (P = 0.036). This
      SNP was also associated with a lower FEV(1) % predicted (57.2 +/- 1.8 for TT vs
      50.8 +/- 2.3 for TA/AA, P = 0.03) and DL(CO) /V(A) (2.89 +/- 0.1 in TT vs 2.53 +/
      0.14 in TA/AA, P = 0.036) in COPD patients. NOD2 gene expression after
      stimulation with 10 ng/mL of tumour necrosis factor-alpha for 4 h, was increased
      to a greater extent in TA/AA genotype than in TT genotype peripheral blood
      neutrophils (P = 0.015). CONCLUSIONS: The NOD2 rs1077861 SNP may influence the
      development and progression of COPD in Japanese subjects.

PMID- 21943071
TI  - The role of cow urine in the oviposition site preference of culicine and
      Anopheles mosquitoes.
AB  - BACKGROUND: Chemical and behavioural ecology of mosquitoes plays an important
      role in the development of chemical cue based vector control. To date, studies
      available have focused on evaluating mosquito attractants and repellents of
      synthetic and human origins. This study, however, was aimed at seasonal
      evaluation of the efficiency of cow urine in producing oviposition cues to
      Anopheles gambiae s.l. and Culex quinquefasciatus in both laboratory and field
      conditions. METHODS: Oviposition response evaluation in laboratory conditions was
      carried out in mosquito rearing cages. The oviposition substrates were located in
      parallel or in diagonal positions inside the cage. Urine evaluation against
      gravid females of An. arabiensis and Cx. quinquefasciatus was carried out at Day
      1, Day 3 and Day 7. Five millilitres (mls) of cow urine was added to oviposition
      substrate while de-chlorinated water was used as a control. In field experiments,
      500 mls of cow urine was added in artificial habitats with 2500 mls of de
      chlorinated water and 2 kgs of soil. The experiment was monitored for thirty
      consecutive days, eggs were collected daily from the habitats at 7.00 hrs. Data
      analysis was performed using parametric and non-parametric tests for treatments
      and controls while attraction of the oviposition substrate in each species was
      presented using Oviposition Activity Index (OAI). RESULTS: The OAI was positive
      with ageing of cattle urine in culicine species in both laboratory and field
      experiments. The OAI for anopheline species was positive with fresh urine. The
      OAI during the rainy season was positive for all species tested while in the dry
      season the OAI for culicine spp and Anopheles gambiae s.l., changed with time
      from positive to negative values.Based on linear model analysis, seasons and
      treatments had a significant effect on the number of eggs laid in habitats, even
      though the number of days had no effect. CONCLUSION: Oviposition substrates
      treated with cow urine in both laboratory and field conditions have shown that
      cow urine left to age from 1-7 days has an influence on oviposition behavioural
      response in mosquitoes. The analysis of microbial colonies for decaying urine
      should be investigated along with its associated by-products.

PMID- 21943072
TI  - A bacterial genome in transition--an exceptional enrichment of IS elements but
      lack of evidence for recent transposition in the symbiont Amoebophilus asiaticus.
AB  - BACKGROUND: Insertion sequence (IS) elements are important mediators of genome
      plasticity and are widespread among bacterial and archaeal genomes. The 1.88 Mbp
      genome of the obligate intracellular amoeba symbiont Amoebophilus asiaticus
      contains an unusually large number of transposase genes (n = 354; 23% of all
      genes). RESULTS: The transposase genes in the A. asiaticus genome can be assigned
      to 16 different IS elements termed ISCaa1 to ISCaa16, which are represented by 2
      to 24 full-length copies, respectively. Despite this high IS element load, the A.
      asiaticus genome displays a GC skew pattern typical for most bacterial genomes,
      indicating that no major rearrangements have occurred recently. Additionally, the
      high sequence divergence of some IS elements, the high number of truncated IS
      element copies (n = 143), as well as the absence of direct repeats in most IS
      elements suggest that the IS elements of A. asiaticus are transpositionally
      inactive. Although we could show transcription of 13 IS elements, we did not find
      experimental evidence for transpositional activity, corroborating our results
      from sequence analyses. However, we detected contiguous transcripts between IS
      elements and their downstream genes at nine loci in the A. asiaticus genome,
      indicating that some IS elements influence the transcription of downstream genes,
      some of which might be important for host cell interaction. CONCLUSIONS: Taken
      together, the IS elements in the A. asiaticus genome are currently in the process
      of degradation and largely represent reflections of the evolutionary past of A.
      asiaticus in which its genome was shaped by their activity.

PMID- 21943070
TI  - Distinct roles of CD4+ T cell subpopulations in retroviral immunity: lessons from
      the Friend virus mouse model.
AB  - It is well established that CD4(+) T cells play an important role in immunity to
      infections with retroviruses such as HIV. However, in recent years CD4(+) T cells
      have been subdivided into several distinct populations that are differentially
      regulated and perform widely varying functions. Thus, it is important to
      delineate the separate roles of these subsets, which range from direct antiviral
      activities to potent immunosuppression. In this review, we discuss contributions
      from the major CD4(+) T cell subpopulations to retroviral immunity. Fundamental
      concepts obtained from studies on numerous viral infections are presented along
      with a more detailed analysis of studies on murine Friend virus. The relevance of
      these studies to HIV immunology and immunotherapy is reviewed.

PMID- 21943073
TI  - The use of reproductive healthcare at commune health stations in a changing
      health system in Vietnam.
AB  - BACKGROUND: With health sector reform in Vietnam moving towards greater
      pluralism, commune health stations (CHSs) have been subject to growing
      competition from private health services and increasing numbers of patients
      bypassing CHSs for higher-level health facilities. This study describes the
      pattern of reproductive health (RH) and family planning (FP) service utilization
      among women at CHSs and other health facilities, and explores socio-demographic
      determinants of RH service utilization at the CHS level. METHODS: This study was
      based on a cross-sectional survey conducted in Thua Thien Hue and Vinh Long
      provinces, using a multi-stage cluster sampling technique. Questionnaire-based
      interviews with 978 ever-married women at reproductive age provided data on socio
      demographic characteristics, current use of FP methods, history of RH service
      use, and the health facility attended for their most recent services. Multiple
      logistic regression analyses were used to identify socio-demographic determinants
      of their use of CHS RH services. RESULTS: Eighty nine percent of ever-married
      women reported current use of birth control with 49% choosing intra-uterine
      device (IUD). Eighty nine percent of pregnant women attended facility-based
      antenatal care (ANC) with 62% having at least 3 check-ups during their latest
      pregnancy. Ninety one percent of mothers had their last delivery in a health
      facility. Seventy-one percent of respondents used CHS for IUD insertion, 55% for
      antenatal check-ups, and 77% gynecological examination. District and
      provincial/central hospitals dominated the provision of delivery service, used by
      57% of mothers for their latest delivery. The percentage of women opting for
      private ANC services was reported at 35%, though the use of private delivery
      services was low (11%). Women who were farmers, earning a lower income, having
      more than 2 children, and living in a rural area were more likely than others to
      use ANC, delivery, and/or gynecological check-up services at the CHS.
      CONCLUSIONS: Women choice of providers for FP and RH services that help them plan
      and protect their pregnancies is driven by socio-economic factors. While the CHS
      retains significant utilization rates, it is under challenge by preferences for
      hospital-based delivery and the growing use of private ANC services.

PMID- 21943074
TI  - Aurora kinases are expressed in medullary thyroid carcinoma (MTC) and their
      inhibition suppresses in vitro growth and tumorigenicity of the MTC derived cell
      line TT.
AB  - BACKGROUND: The Aurora kinase family members, Aurora-A, -B and -C, are involved
      in the regulation of mitosis, and alterations in their expression are associated
      with cell malignant transformation. To date no information on the expression of
      these proteins in medullary thyroid carcinoma (MTC) are available. We here
      investigated the expression of the Aurora kinases in human MTC tissues and their
      potential use as therapeutic targets. METHODS: The expression of the Aurora
      kinases in 26 MTC tissues at different TNM stages was analyzed at the mRNA level
      by quantitative RT-PCR. We then evaluated the effects of the Aurora kinase
      inhibitor MK-0457 on the MTC derived TT cell line proliferation, apoptosis, soft
      agar colony formation, cell cycle and ploidy. RESULTS: The results showed the
      absence of correlation between tumor tissue levels of any Aurora kinase and tumor
      stage indicating the lack of prognostic value for these proteins. Treatment with
      MK-0457 inhibited TT cell proliferation in a time- and dose-dependent manner with
      IC50 = 49.8 +/- 6.6 nM, as well as Aurora kinases phosphorylation of substrates
      relevant to the mitotic progression. Time-lapse experiments demonstrated that MK
      0457-treated cells entered mitosis but were unable to complete it.
      Cytofluorimetric analysis confirmed that MK-0457 induced accumulation of cells
      with >= 4N DNA content without inducing apoptosis. Finally, MK-0457 prevented the
      capability of the TT cells to form colonies in soft agar. CONCLUSIONS: We
      demonstrate that Aurora kinases inhibition hampered growth and tumorigenicity of
      TT cells, suggesting its potential therapeutic value for MTC treatment.

PMID- 21943075
TI  - Increased attendance rates and altered characteristics of sexual violence.
AB  - OBJECTIVE: To study the attendance rates and characteristics of sexual violence
      presented at emergency services for rape victims, over a 10-year period. DESIGN:
      Incidence study. SETTING: Rape Trauma Service, within an emergency department at
      a tertiary referral university hospital. POPULATION. The total female population
      in Iceland. METHODS: Medical records on visits were reviewed and systematically
      coded. Annual attendance rates were calculated over time as number of visits per
      10 000 female inhabitants aged 13-49 years. Characteristics of sexual violence,
      perpetrators and victims were compared between 1998-2002 and 2003-2007. MAIN
      OUTCOME MEASURES: Annual attendance rates and characteristics of sexual violence.
      RESULTS: Of 1153 visits, 828 (71.8%) were due to severe sexual violence
      (penetration). Annual attendance rates of all sexual violence increased from 12.5
      to 16.9 per 10 000 women aged 13-49 (p<0.01). Attendance rates due to severe
      sexual violence increased specifically among women aged 18-25 (p<0.01). The
      proportion of assaults involving multiple perpetrators increased from 13.9% in
      1998-2002 to 18.9% in 2003-2007 (p=0.05). With time, a higher proportion of
      victims had seriously impaired consciousness due to alcohol consumption (p<0.01)
      and had used illegal drugs prior to assault (p<0.05). CONCLUSIONS: The findings
      point towards an increase in women's visits to specialized emergency services for
      rape victims, particularly in the age group 18-25 years. The increased role of
      multiple perpetrators, alcohol and illicit drugs in sexual violence calls for
      further attention.

PMID- 21943076
TI  - Adult male circumcision as an intervention against HIV: an operational study of
      uptake in a South African community (ANRS 12126).
AB  - BACKGROUND: To evaluate the knowledge, attitudes and beliefs about adult male
      circumcision (AMC), assess the association of AMC with HIV incidence and
      prevalence, and estimate AMC uptake in a Southern African community. METHODS: A
      cross-sectional biomedical survey (ANRS-12126) conducted in 2007-2008 among a
      random sample of 1198 men aged 15 to 49 from Orange Farm (South Africa). Face-to
      face interviews were conducted by structured questionnaire. Recent HIV infections
      were evaluated using the BED incidence assay. Circumcision status was self
      reported and clinically assessed. Adjusted HIV incidence rate ratios (aIRR) and
      prevalence ratios (aPR) were calculated using Poisson regression. RESULTS: The
      response rate was 73.9%. Most respondents agreed that circumcised men could
      become HIV infected and needed to use condoms, although 19.3% (95%CI: 17.1% to
      21.6%) asserted that AMC protected fully against HIV. Among self-reported
      circumcised men, 44.9% (95%CI: 39.6% to 50.3%) had intact foreskins. Men without
      foreskins had lower HIV incidence and prevalence than men with foreskins (aIRR =
      0.35; 95%CI: 0.14 to 0.88; aPR = 0.45, 95%CI: 0.26 to 0.79). No significant
      difference was found between self-reported circumcised men with foreskins and
      other uncircumcised men. Intention to undergo AMC was associated with ethnic
      group and partner and family support of AMC. Uptake of AMC was 58.8% (95%CI:
      55.4% to 62.0%). CONCLUSIONS: AMC uptake in this community is high but
      communication and counseling should emphasize what clinical AMC is and its effect
      on HIV acquisition. These findings suggest that AMC roll-out is promising but
      requires careful implementation strategies to be successful against the African
      HIV epidemic.

PMID- 21943077
TI  - Pre-operative echocardiogram in hip fracture patients with cardiac murmur--an
      audit.
AB  - BACKGROUND: All hip fracture patients with a cardiac murmur have an
      echocardiogram as a part of their preoperative work-up in our unit. We performed
      a retrospective audit to assess the impact of obtaining a pre-operative
      echocardiogram on the management of hip fracture patients. METHODS: All hip
      fracture patients (N = 349) between 01/06/08 and 01/06/09 were included in the
      study. 29 patients had pre-operative echocardiogram (echo group). A computer
      generated randomised sample of 40 patients was generated from N, 'non-echo'
      group. Data was obtained from medical records and the Hospital Information
      Support System (HISS). The groups were compared using Student's t test. Approval
      was obtained locally from the clinical governance department for this project.
      RESULTS: Age and gender distribution were similar in both groups. Indication for
      echo was an acute cardiac abnormality in 4 cases. 25 patients had echo for no new
      cardiac problem (indication being cardiac murmur in 23 patients and extensive
      cardiac history in 2 cases). Cardiology opinion was sought in 5 cases. No patient
      required cardiac surgery or balloon angioplasty preoperatively. Patients having
      pre-operative echo had significant delay to surgery (average 2.7 days, range 0-6
      days) compared to 'non-echo' group (average 1.1 days, range 0-3 days), (p <
      0.001). There was no significant difference in length of stay (p = 0.14) and
      mortality at 30 days (p = 0.41) between the groups. CONCLUSION: We have developed
      departmental guidelines for expediting echo requests in hip fracture patients
      with cardiac murmur. A liaison has been established with our cardiology
      department to prioritise such patients on the Echocardiography waiting list, to
      prevent unnecessary avoidable delay. Careful patient selection for pre-operative
      echocardiography is important to avoid unnecessary delay to surgery.

PMID- 21943079
TI  - Elucidating the spatially varying relation between cervical cancer and socio
      economic conditions in England.
AB  - BACKGROUND: Geographically weighted Poisson regression (GWPR) was applied to the
      relation between cervical cancer disease incidence rates in England and socio
      economic deprivation, social status and family structure covariates. Local
      parameters were estimated which describe the spatial variation in the relations
      between incidence and socio-economic covariates. RESULTS: A global (stationary)
      regression model revealed a significant correlation between cervical cancer
      incidence rates and social status. However, a local (non-stationary) GWPR model
      provided a better fit with less spatial correlation (positive autocorrelation) in
      the residuals. Moreover, the GWPR model was able to represent local variation in
      the relations between cervical cancer incidence and socio-economic covariates
      across space, whereas the global model represented only the overall (or average)
      relation for the whole of England. The global model could lead to
      misinterpretation of the relations between cervical cancer incidence and socio
      economic covariates locally. CONCLUSIONS: Cervical cancer incidence was shown to
      have a non-stationary relationship with spatially varying covariates that are
      available through national datasets. As a result, it was shown that if low social
      status sectors of the population are to be targeted preferentially, this
      targeting should be done on a region-by-region basis such as to optimize health
      outcomes. While such a strategy may be difficult to implement in practice, the
      research does highlight the inequalities inherent in a uniform intervention
      approach.

PMID- 21943078
TI  - Prevention of siderophore- mediated gut-derived sepsis due to P. aeruginosa can
      be achieved without iron provision by maintaining local phosphate abundance: role
      of pH.
AB  - BACKGROUND: During extreme physiological stress, the intestinal tract can be
      transformed into a harsh environment characterized by regio- spatial alterations
      in oxygen, pH, and phosphate concentration. When the human intestine is exposed
      to extreme medical interventions, the normal flora becomes replaced by pathogenic
      species whose virulence can be triggered by various physico-chemical cues leading
      to lethal sepsis. We previously demonstrated that phosphate depletion develops in
      the mouse intestine following surgical injury and triggers intestinal P.
      aeruginosa to express a lethal phenotype that can be prevented by oral phosphate
      ([Pi]) supplementation. RESULTS: In this study we examined the role of pH in the
      protective effect of [Pi] supplementation as it has been shown to be increased in
      the distal gut following surgical injury. Surgically injured mice drinking 25 mM
      [Pi] at pH 7.5 and intestinally inoculated with P. aeruginosa had increased
      mortality compared to mice drinking 25 mM [Pi] at pH 6.0 (p < 0.05). This finding
      was confirmed in C. elegans. Transcriptional analysis of P. aeruginosa
      demonstrated enhanced expression of various genes involved in media alkalization
      at pH 6.0 and a global increase in the expression of all iron-related genes at pH
      7.5. Maintaining the pH at 6.0 via phosphate supplementation led to significant
      attenuation of iron-related genes as demonstrated by microarray and confirmed by
      QRT-PCR analyses. CONCLUSION: Taken together, these data demonstrate that
      increase in pH in distal intestine of physiologically stressed host colonized by
      P. aeruginosa can lead to the expression of siderophore-related virulence in
      bacteria that can be prevented without providing iron by maintaining local
      phosphate abundance at pH 6.0. This finding is particularly important as
      provision of exogenous iron has been shown to have untoward effects when
      administered to critically ill and septic patients. Given that phosphate, pH, and
      iron are near universal cues that dictate the virulence status of a broad range
      of microorganisms relevant to serious gut origin infection and sepsis in
      critically ill patients, the maintenance of phosphate and pH at appropriate
      physiologic levels to prevent virulence activation in a site specific manner can
      be considered as a novel anti-infective therapy in at risk patients.

PMID- 21943080
TI  - Water outage increases the risk of gastroenteritis and eyes and skin diseases.
AB  - BACKGROUND: The present study used insurance claims data to investigate
      infections associated with short-term water outage because of constructions or
      pipe breaks. METHODS: The present study used medical claims of one million
      insured persons for 2004-2006. We estimated incidences of gastroenteritis and eye
      and skin complaints for 10 days before, during, and after 10 days of water supply
      restriction for outpatient visits and for emergency and in-patient care combined.
      RESULTS: There was an increase in medical services for these complaints in
      outpatient visits because of water outages. Poisson regression analyses showed
      that increased risks of medical services were significant for gastroenteritis
      (relative risk [RR] 1.31, 95% confidence interval [CI] 1.26-1.37), skin disease
      (RR 1.36, 95% CI 1.30-1.42), and eye disease patients (RR 1.34, 95% CI 1.26
      1.44). Similar risks were observed during 10-day lag periods. Compared with those
      in cool days, risks of medical services are higher when average daily temperature
      is above 30  degrees C for gastroenteritis (RR 12.1, 95% CI 6.17-23.7), skin
      diseases (RR 4.48, 95% CI 2.29-8.78), and eye diseases (RR 40.3, 95% CI 7.23
      224). CONCLUSION: We suggest promoting personal hygiene education during water
      supply shortages, particularly during the warm months.

PMID- 21943081
TI  - It's all about the children: a participant-driven photo-elicitation study of
      Mexican-origin mothers' food choices.
AB  - BACKGROUND: There is a desperate need to address diet-related chronic diseases in
      Mexican-origin women, particularly for those in border region colonias (Mexican
      settlements) and other new destination communities in rural and non-rural areas
      of the U.S. Understanding the food choices of mothers, who lead food and health
      activities in their families, provides one way to improve health outcomes in
      Mexican-origin women and their children. This study used a visual method,
      participant-driven photo-elicitation, and grounded theory in a contextual study
      of food choices from the perspectives of Mexican-origin mothers. METHODS: Teams
      of trained promotoras (female community health workers from the area) collected
      all data in Spanish. Ten Mexican-origin mothers living in colonias in Hidalgo
      County, TX completed a creative photography assignment and an in-depth interview
      using their photographs as visual prompts and examples. English transcripts were
      coded inductively by hand, and initial observations emphasized the salience of
      mothers' food practices in their routine care-giving. This was explored further
      by coding transcripts in the qualitative data analysis software Atlas.ti.
      RESULTS: An inductive conceptual framework was created to provide context for
      understanding mothers' daily practices and their food practices in particular.
      Three themes emerged from the data: 1) a mother's primary orientation was toward
      her children; 2) leveraging resources to provide the best for her children; and
      3) a mother's daily food practices kept her children happy, healthy, and well
      fed. Results offer insight into the intricate meanings embedded in Mexican-origin
      mothers' routine food choices. CONCLUSIONS: This paper provides a new perspective
      for understanding food choice through the eyes of mothers living in the colonias
      of South Texas -- one that emphasizes the importance of children in their routine
      food practices and the resilience of the mothers themselves. Additional research
      is needed to better understand mothers' perspectives and food practices with
      larger samples of women and among other socioeconomic groups.

PMID- 21943082
TI  - Assessing food appeal and desire to eat: the effects of portion size & energy
      density.
AB  - BACKGROUND: Visual presentation of food provides considerable information such as
      its potential for palatability and availability, both of which can impact eating
      behavior. METHODS: We investigated the subjective ratings for food appeal and
      desire to eat when exposed to food pictures in a fed sample (n=129) using the
      computer paradigm ImageRate. Food appeal and desire to eat were analyzed for the
      effects of food group, portion size and energy density of the foods presented as
      well as by participant characteristics. RESULTS: Food appeal ratings were
      significantly higher than those for desire to eat (57.9+/-11.6 v. 44.7+/-18.0;
      p<0.05). Body mass index was positively correlated to desire to eat (r=0.20;
      p<0.05), but not food appeal. Food category analyses revealed that fruit was the
      highest rated food category for both appeal and desire, followed by discretionary
      foods. Additionally, overweight individuals reported higher ratings of desire to
      eat large portions of food compared to smaller portions (p<0.001), although these
      effects were relatively small. Energy density of the foods was inversely
      correlated with ratings for both appeal and desire (r's=-0.27; p's<0.01).
      CONCLUSIONS: Results support the hypothesis that individuals differentiate
      between food appeal and desire to eat foods when assessing these ratings using
      the same type of metric. Additionally, relations among food appeal and desire to
      eat ratings and body mass show overweight individuals could be more responsive to
      visual foods cues in a manner that contributes to obesity.

PMID- 21943083
TI  - Maternal affect and quality of parenting experiences are related to amygdala
      response to infant faces.
AB  - We examined how individual differences in mood and anxiety in the early
      postpartum period are related to brain response to infant stimuli during fMRI,
      with particular focus on regions implicated in both maternal behavior and
      mood/anxiety, that is, the subgenual anterior cingulate cortex (sgACC) and the
      amygdala. At approximately 3 months postpartum, 22 mothers completed an affect
      rating task (ART) during fMRI, where their affective response to infant stimuli
      was explicitly probed. Mothers viewed/rated four infant face conditions: own
      positive (OP), own negative (ON), unfamiliar positive (UP), and unfamiliar
      negative (UN). Mood and anxiety were measured by the Edinburgh Postnatal
      Depression Scale (EDPS) and the State-Trait Anxiety Inventory-Trait Version (STAI
      T); maternal factors related to parental stress and attachment were also
      assessed. Brain-imaging data underwent a random-effects analysis, and cluster
      based statistical thresholding was applied to the following contrasts: OP-UP, ON
      UN, OP-ON, and UP-UN. Our main finding was that poorer quality of maternal
      experience was significantly related to reduced amygdala response to OP compared
      to UP infant faces. Our results suggest that, in human mothers, infant-related
      amygdala function may be an important factor in maternal anxiety/mood, in quality
      of mothering, and in individual differences in the motivation to mother. We are
      very grateful to the staff at the Imaging Research Center of the Brain-Body
      Institute for their contributions to this project. This work was supported by an
      Ontario Mental Health Foundation operating grant awarded to Alison Fleming and a
      postdoctoral fellowship awarded to Jennifer Barrett. 

PMID- 21943084
TI  - Self Management Activation Randomised Trial for Prostatitis (SMART-P): study
      protocol for a randomised controlled trial.
AB  - BACKGROUND: Chronic prostatitis otherwise known as chronic pelvic pain syndrome
      is a common urological diagnosis that causes many men significant morbidity and
      has a detrimental effect on their quality of life. Standard treatment with
      antibiotics and simple analgesia are often ineffective and many patients are
      managed by the chronic pain services.Cognitive behavioural therapy has been shown
      to be helpful in the management of many chronic diseases and has recently been
      proposed as an effective treatment for chronic prostatitis. Furthermore, a self
      management programme administered to groups of men with lower urinary tract
      symptoms has been shown to be more effective than standard treatments including
      surgery.Therefore, we have developed a cognitive behavioural therapy programme
      specifically for men with chronic prostatitis. This novel treatment approach will
      be compared to conventional therapy in the pain clinic such as atypical analgesia
      and local anaesthetic injections in the context of a randomised controlled trial.
      METHODS/DESIGN: Men will be recruited from general urology outpatient clinics
      following the exclusion of other diagnoses that could be responsible for their
      symptoms. Men will be randomised to attend either a self management healthcare
      and education programme or to pain clinic referral alone. The self management
      programme will be administered by a clinical psychologist to small groups of men
      over six consecutive weekly sessions each lasting two hours. Patients will be
      taught techniques of problem-solving and goal-setting and will learn coping
      mechanisms and how to modify catastrophic cognition.The primary outcome will be
      change from baseline in the National Institute of Health Chronic Prostatitis
      Symptom Index, a validated instrument for the assessment of men with chronic
      prostatitis. Secondary outcomes include generic quality of life scores and
      analgesic and drug usage. Outcomes will be assessed at 2, 6 and 12 months.
      DISCUSSION: If this group administered self management programme is shown to be
      effective in the treatment of men with chronic prostatitis it may become the new
      standard of care for these patients. Furthermore, it may be adapted for use in
      women with interstitial cystitis, a condition which is analogous to chronic
      prostatitis in men. TRIAL REGISTRATION: Current Controlled Trials ISRCTN21012555.

PMID- 21943086
TI  - Diagnosis of pericardial cysts using diffusion weighted magnetic resonance
      imaging: A case series.
AB  - INTRODUCTION: Congenital pericardial cysts are benign lesions that arise from the
      pericardium during embryonic development. The diagnosis is based on typical
      imaging features, but atypical locations and signal magnetic resonance imaging
      sequences make it difficult to exclude other lesions. Diffusion-weighted magnetic
      resonance imaging is a novel method that can be used to differentiate tissues
      based on their restriction to proton diffusion. Its use in differentiating
      pericardial cysts from other pericardial lesions has not yet been described. CASE
      PRESENTATION: We present three cases (a 51-year-old Caucasian woman, a 66-year
      old Caucasian woman and a 77-year-old Caucasian woman) with pericardial cysts
      evaluated with diffusion-weighted imaging using cardiac magnetic resonance
      imaging. Each lesion demonstrated a high apparent diffusion coefficient similar
      to that of free water. CONCLUSION: This case series is the first attempt to
      investigate the utility of diffusion-weighted magnetic resonance imaging in the
      assessment of pericardial cysts. Diffusion-weighted imaging may be a useful
      noninvasive diagnostic tool for pericardial cysts when conventional imaging
      findings are inconclusive.

PMID- 21943085
TI  - The protein interaction map of bacteriophage lambda.
AB  - BACKGROUND: Bacteriophage lambda is a model phage for most other dsDNA phages and
      has been studied for over 60 years. Although it is probably the best
      characterized phage there are still about 20 poorly understood open reading
      frames in its 48-kb genome. For a complete understanding we need to know all
      interactions among its proteins. We have manually curated the lambda literature
      and compiled a total of 33 interactions that have been found among lambda
      proteins. We set out to find out how many protein-protein interactions remain to
      be found in this phage. RESULTS: In order to map lambda's interactions, we have
      cloned 68 out of 73 lambda open reading frames (the "ORFeome") into Gateway
      vectors and systematically tested all proteins for interactions using exhaustive
      array-based yeast two-hybrid screens. These screens identified 97 interactions.
      We found 16 out of 30 previously published interactions (53%). We have also found
      at least 18 new plausible interactions among functionally related proteins. All
      previously found and new interactions are combined into structural and network
      models of phage lambda. CONCLUSIONS: Phage lambda serves as a benchmark for
      future studies of protein interactions among phage, viruses in general, or large
      protein assemblies. We conclude that we could not find all the known interactions
      because they require chaperones, post-translational modifications, or multiple
      proteins for their interactions. The lambda protein network connects 12 proteins
      of unknown function with well characterized proteins, which should shed light on
      the functional associations of these uncharacterized proteins.

PMID- 21943087
TI  - Rate variation and estimation of divergence times using strict and relaxed
      clocks.
AB  - BACKGROUND: Understanding causes of biological diversity may be greatly enhanced
      by knowledge of divergence times. Strict and relaxed clock models are used in
      Bayesian estimation of divergence times. We examined whether: i) strict clock
      models are generally more appropriate in shallow phylogenies where rate variation
      is expected to be low, ii) the likelihood ratio test of the clock (LRT) reliably
      informs which model is appropriate for dating divergence times. Strict and
      relaxed models were used to analyse sequences simulated under different levels of
      rate variation. Published shallow phylogenies (Black bass, Primate-sucking lice,
      Podarcis lizards, Gallotiinae lizards, and Caprinae mammals) were also analysed
      to determine natural levels of rate variation relative to the performance of the
      different models. RESULTS: Strict clock analyses performed well on data simulated
      under the independent rates model when the standard deviation of log rate on
      branches, sigma, was low (<= 0.1), but were inappropriate when sigma>0.1 (95% of
      rates fall within 0.0082-0.0121 subs/site/Ma when sigma = 0.1, for a mean rate of
      0.01). The independent rates relaxed clock model performed well at all levels of
      rate variation, although posterior intervals on times were significantly wider
      than for the strict clock. The strict clock is therefore superior when rate
      variation is low. The performance of a correlated rates relaxed clock model was
      similar to the strict clock. Increased numbers of independent loci led to
      slightly narrower posteriors under the relaxed clock while older root ages
      provided proportionately narrower posteriors. The LRT had low power for sigma =
      0.01-0.1, but high power for sigma = 0.5-2.0. Posterior means of sigma2 were
      useful for assessing rate variation in published datasets. Estimates of natural
      levels of rate variation ranged from 0.05-3.38 for different partitions.
      Differences in divergence times between relaxed and strict clock analyses were
      greater in two datasets with higher sigma2 for one or more partitions, supporting
      the simulation results. CONCLUSIONS: The strict clock can be superior for trees
      with shallow roots because of low levels of rate variation between branches. The
      LRT allows robust assessment of suitability of the clock model as does
      examination of posteriors on sigma2.

PMID- 21943088
TI  - Factors associated with long-term survival of patients with advanced non-small
      cell lung cancer.
AB  - BACKGROUND AND OBJECTIVE: Only a small proportion of patients with advanced non
      small cell lung cancer (NSCLC) have a life expectancy greater than 2 years. The
      aim of this study was to identify the factors associated with long-term survival
      of patients with advanced NSCLC. METHODS: Patients who had received chemotherapy
      for stage IIIb or IV NSCLC that was not amenable to radiotherapy were studied
      retrospectively. Data were gathered prospectively from a comprehensive database.
      Long-term survivors (>2 years) were compared with the other patients, with
      respect to clinical, biological and tumour-node-metastasis criteria. RESULTS:
      Data for 245 consecutive patients were collected. Thirty nine patients (15.9%)
      survived for more than 2 years. Long-term survivors were more likely to have had
      metastases at fewer sites (P = 0.008), an absence of bone metastases (P = 0.01),
      a performance status (PS) of 0-1 at first progression of the tumour (P = 0.002),
      a tumour that was controlled with first (P < 0.0001) and second-line (P = 0.004)
      chemotherapy, maintenance therapy (P = 0.001), curative surgery (P < 0.0001),
      time to first progression of the tumour of >3 months (P < 0.0001), normal LDH
      levels at diagnosis (P = 0.049), and a haemoglobin concentration >110 g/L at
      first progression of the tumour (P = 0.02). In multivariate analysis, surgery,
      maintenance treatment, time to first progression of the tumour of >3 months, a PS
      of 0-1 at first progression, the number of chemotherapy agents received, and LDH
      levels, were significant predictors of long-term survival. CONCLUSIONS:  
      Assessment of these factors, and the use of maintenance therapy, when possible,
      may identify a population of patients with NSCLC that is likely to have a
      prolonged life expectancy.

PMID- 21943089
TI  - The physiologic responses to epinephrine during cooling and after rewarming in
      vivo.
AB  - INTRODUCTION: The purpose of our study was to determine whether hypothermia has
      any effects on physiological hemodynamic responses to epinephrine (Epi), and
      whether rewarming reverses these effects. METHODS: Sprague-Dawley rats were
      instrumented to measure mean arterial pressure (MAP), and left ventricular (LV)
      pressure-volume changes were recorded by using a Millar pressure-volume
      conductance catheter. Core temperature was reduced from 37 degrees C to 28
      degrees C and returned to 37 degrees C by using both internal and external heat
      exchangers. Two groups of rats were infused with either saline (n = 7), or Epi
      0.125 MUg/min continuously (n = 7). At 33 degrees C, 30 degrees C, and 28 degrees
      C, the Epi infusion was temporarily increased from 0.125 to 1.25 MUg/min.
      RESULTS: Before cooling, Epi infusion in both groups resulted in a significant,
      dose-dependent increase in heart rate (HR), stroke volume (SV), cardiac output
      (CO), LV dP/dtmax (maximum derivative of systolic pressure over time), but only
      Epi infusion at 1.25 MUg/min caused elevation of MAP. During cooling to 30
      degrees C, Epi infusion at 0.125 MUg/min caused a significant elevation of
      central hemodynamic variables, whereas MAP remained unchanged. In contrast, Epi
      infusions at 1.25 MUg/min caused a significant elevation of MAP during cooling to
      28 degrees C but no increases in central hemodynamics. After rewarming, all
      hemodynamic variables returned to baseline in both groups, but only the saline
      treated animals displayed the prehypothermic hemodynamic dose responses to Epi
      infusions. CONCLUSIONS: This study shows that hypothermia causes a change in the
      physiological hemodynamic response to Epi, which is not reversed by rewarming.

PMID- 21943090
TI  - The calcar screw in angular stable plate fixation of proximal humeral fractures-
      a case study.
AB  - BACKGROUND: With new minimally-invasive approaches for angular stable plate
      fixation of proximal humeral fractures, the need for the placement of oblique
      inferomedial screws ('calcar screw') has increasingly been discussed. The purpose
      of this study was to investigate the influence of calcar screws on secondary loss
      of reduction and on the occurrence of complications. METHODS: Patients with a
      proximal humeral fracture who underwent angular stable plate fixation between
      01/2007 and 07/2009 were included. On AP views of the shoulder, the difference in
      height between humeral head and the proximal end of the plate were determined
      postoperatively and at follow-up. Additionally, the occurrence of complications
      was documented. Patients with calcar screws were assigned to group C+, patients
      without to group C-. RESULTS: Follow-up was possible in 60 patients (C+ 6.7 +/-
      5.6 M/C- 5.0 +/- 2.8 M). Humeral head necrosis occurred in 6 (C+, 15.4%) and 3 (C
      , 14.3%) cases. Cut-out of the proximal screws was observed in 3 (C+, 7.7%) and 1
      (C-, 4.8%) cases. In each group, 1 patient showed delayed union. Implant failure
      or lesions of the axillary nerve were not observed. In 44 patients, true AP and
      Neer views were available to measure the head-plate distance. There was a
      significant loss of reduction in group C- (2.56 +/- 2.65 mm) compared to C+ (0.77
      +/- 1.44 mm; p = 0.01). CONCLUSIONS: The placement of calcar screws in the
      angular stable plate fixation of proximal humeral fractures is associated with
      less secondary loss of reduction by providing inferomedial support. An increased
      risk for complications could not be shown.

PMID- 21943091
TI  - High specificity of line-immunoassay based algorithms for recent HIV-1 infection
      independent of viral subtype and stage of disease.
AB  - BACKGROUND: Serologic testing algorithms for recent HIV seroconversion (STARHS)
      provide important information for HIV surveillance. We have shown that a
      patient's antibody reaction in a confirmatory line immunoassay (INNO-LIA HIV I/II
      Score, Innogenetics) provides information on the duration of infection. Here, we
      sought to further investigate the diagnostic specificity of various Inno-Lia
      algorithms and to identify factors affecting it. METHODS: Plasma samples of 714
      selected patients of the Swiss HIV Cohort Study infected for longer than 12
      months and representing all viral clades and stages of chronic HIV-1 infection
      were tested blindly by Inno-Lia and classified as either incident (up to 12 m) or
      older infection by 24 different algorithms. Of the total, 524 patients received
      HAART, 308 had HIV-1 RNA below 50 copies/mL, and 620 were infected by a HIV-1 non
      B clade. Using logistic regression analysis we evaluated factors that might
      affect the specificity of these algorithms. RESULTS: HIV-1 RNA < 50 copies/mL was
      associated with significantly lower reactivity to all five HIV-1 antigens of the
      Inno-Lia and impaired specificity of most algorithms. Among 412 patients either
      untreated or with HIV-1 RNA >= 50 copies/mL despite HAART, the median specificity
      of the algorithms was 96.5% (range 92.0-100%). The only factor that significantly
      promoted false-incident results in this group was age, with false-incident
      results increasing by a few percent per additional year. HIV-1 clade, HIV-1 RNA,
      CD4 percentage, sex, disease stage, and testing modalities exhibited no
      significance. Results were similar among 190 untreated patients. CONCLUSIONS: The
      specificity of most Inno-Lia algorithms was high and not affected by HIV-1
      variability, advanced disease and other factors promoting false-recent results in
      other STARHS. Specificity should be good in any group of untreated HIV-1
      patients.

PMID- 21943092
TI  - A phenanthrene derived PARP inhibitor is an extra-centrosomes de-clustering agent
      exclusively eradicating human cancer cells.
AB  - BACKGROUND: Cells of most human cancers have supernumerary centrosomes. To enable
      an accurate chromosome segregation and cell division, these cells developed a yet
      unresolved molecular mechanism, clustering their extra centrosomes at two poles,
      thereby mimicking mitosis in normal cells. Failure of this bipolar centrosome
      clustering causes multipolar spindle structures and aberrant chromosomes
      segregation that prevent normal cell division and lead to 'mitotic catastrophe
      cell death'. METHODS: We used cell biology and biochemical methods, including
      flow cytometry, immunocytochemistry and live confocal imaging. RESULTS: We
      identified a phenanthrene derived PARP inhibitor, known for its activity in
      neuroprotection under stress conditions, which exclusively eradicated multi
      centrosomal human cancer cells (mammary, colon, lung, pancreas, ovarian) while
      acting as extra-centrosomes de-clustering agent in mitosis. Normal human
      proliferating cells (endothelial, epithelial and mesenchymal cells) were not
      impaired. Despite acting as PARP inhibitor, the cytotoxic activity of this
      molecule in cancer cells was not attributed to PARP inhibition alone. CONCLUSION:
      We identified a water soluble phenanthridine that exclusively targets the unique
      dependence of most human cancer cells on their supernumerary centrosomes bi-polar
      clustering for their survival. This paves the way for a new selective cancer
      targeting therapy, efficient in a wide range of human cancers.

PMID- 21943093
TI  - The economic benefits of reducing physical inactivity: an Australian example.
AB  - BACKGROUND: Physical inactivity has major impacts on health and productivity. Our
      aim was to estimate the health and economic benefits of reducing the prevalence
      of physical inactivity in the 2008 Australian adult population. The economic
      benefits were estimated as 'opportunity cost savings', which represent resources
      utilized in the treatment of preventable disease that are potentially available
      for re-direction to another purpose from fewer incident cases of disease
      occurring in communities. METHODS: Simulation models were developed to show the
      effect of a 10% feasible, reduction target for physical inactivity from current
      Australian levels (70%). Lifetime cohort health benefits were estimated as fewer
      incident cases of inactivity-related diseases; deaths; and Disability Adjusted
      Life Years (DALYs) by age and sex. Opportunity costs were estimated as health
      sector cost impacts, as well as paid and unpaid production gains and leisure
      impacts from fewer disease events associated with reduced physical inactivity.
      Workforce production gains were estimated by comparing surveyed participation and
      absenteeism rates of physically active and inactive adults, and valued using the
      friction cost approach. The impact of an improvement in health status on unpaid
      household production and leisure time were modeled from time use survey data, as
      applied to the exposed and non-exposed population subgroups and valued by
      suitable proxy. Potential costs associated with interventions to increase
      physical activity were not included. Multivariable uncertainty analyses and
      univariate sensitivity analyses were undertaken to provide information on the
      strength of the conclusions. RESULTS: A 10% reduction in physical inactivity
      would result in 6,000 fewer incident cases of disease, 2,000 fewer deaths, 25,000
      fewer DALYs and provide gains in working days (114,000), days of home-based
      production (180,000) while conferring a AUD96 million reduction in health sector
      costs. Lifetime potential opportunity cost savings in workforce production (AUD12
      million), home-based production (AUD71 million) and leisure-based production
      (AUD79 million) was estimated (total AUD162 million 95% uncertainty interval
      AUD136 million, AUD196 million). CONCLUSIONS: Opportunity cost savings and health
      benefits conservatively estimated from a reduction in population-level physical
      inactivity may be substantial. The largest savings will benefit individuals in
      the form of unpaid production and leisure gains, followed by the health sector,
      business and government.

PMID- 21943094
TI  - Inhibition of voltage-gated Na(+)  currents in sensory neurones by the sea
      anemone toxin APETx2.
AB  - BACKGROUND AND PURPOSE: APETx2, a toxin from the sea anemone Anthropleura
      elegantissima, inhibits acid-sensing ion channel 3 (ASIC3)-containing homo- and
      heterotrimeric channels with IC(50) values < 100 nM and 0.1-2 uM respectively.
      ASIC3 channels mediate acute acid-induced and inflammatory pain response and
      APETx2 has been used as a selective pharmacological tool in animal studies.
      Toxins from sea anemones also modulate voltage-gated Na(+) channel (Na(v) )
      function. Here we tested the effects of APETx2 on Na(v) function in sensory
      neurones. EXPERIMENTAL APPROACH: Effects of APETx2 on Na(v) function were studied
      in rat dorsal root ganglion (DRG) neurones by whole-cell patch clamp. KEY
      RESULTS: APETx2 inhibited the tetrodotoxin (TTX)-resistant Na(v) 1.8 currents of
      DRG neurones (IC(50) , 2.6 uM). TTX-sensitive currents were less inhibited. The
      inhibition of Na(v) 1.8 currents was due to a rightward shift in the voltage
      dependence of activation and a reduction of the maximal macroscopic conductance.
      The inhibition of Na(v) 1.8 currents by APETx2 was confirmed with cloned channels
      expressed in Xenopus oocytes. In current-clamp experiments in DRG neurones, the
      number of action potentials induced by injection of a current ramp was reduced by
      APETx2. CONCLUSIONS AND IMPLICATIONS: APETx2 inhibited Na(v) 1.8 channels, in
      addition to ASIC3 channels, at concentrations used in in vivo studies. The
      limited specificity of this toxin should be taken into account when using APETx2
      as a pharmacological tool. Its dual action will be an advantage for the use of
      APETx2 or its derivatives as analgesic drugs.

PMID- 21943095
TI  - A review of studies of parent-child communication about sexuality and HIV/AIDS in
      sub-Saharan Africa.
AB  - Parent-child sexuality communication has been identified as a protective factor
      for adolescent sexual and reproductive health, including HIV infection. The
      available literature on this topic in sub-Saharan Africa is increasing; however a
      systematic review of studies has not been conducted. This article reviews the
      literature in the area of parental or caregiver and child communication about
      sexuality and HIV/AIDS in sub-Saharan Africa. A review of peer reviewed
      literature published between 1980 and April 2011 was conducted. Communication
      process studies investigating the frequency, content, style, tone of discussions,
      preferences, as well as associations with and barriers to sexuality communication
      are reviewed. In addition, studies which examine behavioral associations with
      parent-child sexuality communication, and intervention studies to improve parent
      child sexuality communication are examined. The findings from process studies
      suggest wide variation in terms of frequency of discussions, with a range of
      socio-demographic and other factors associated with sexuality communication.
      Overall, findings demonstrate that discussions tend to be authoritarian and uni
      directional, characterized by vague warnings rather than direct, open discussion.
      Moreover, parents and young people report a number of barriers to open dialogue,
      including lack of knowledge and skills, as well as cultural norms and taboos.
      Findings are less clear when it comes to associations between parental
      communication and adolescent sexual activity and contraception use. However,
      nascent indications from intervention research suggest positive findings with
      increases in frequency and comfort of discussions, among other outcomes. Gaps in
      the research are identified and discussed with implications for future studies.

PMID- 21943096
TI  - Distribution and genetic variation of hymenolepidid cestodes in murid rodents on
      the Canary Islands (Spain).
AB  - BACKGROUND: In the Canary Islands there are no previous data about tapeworms
      (Cestoda) of rodents. In order to identify the hymenolepidid species present in
      these hosts, a survey of 1,017 murine (349 Rattus rattus, 13 Rattus norvegicus
      and 655 Mus musculus domesticus) was carried out in the whole Archipelago.
      Molecular studies based on nuclear ITS1 and mitochondrial COI loci were performed
      to confirm the identifications and to analyse the levels of genetic variation and
      differentiation. RESULTS: Three species of hymenolepidids were identified:
      Hymenolepis diminuta, Rodentolepis microstoma and Rodentolepis fraterna.
      Hymenolepis diminuta (in rats) and R. microstoma (in mice) showed a widespread
      distribution in the Archipelago, and R. fraterna was the least spread species,
      appearing only on five of the islands. The hymenolepidids found on Fuerteventura,
      Lanzarote and La Graciosa were restricted to one area. The COI network of H.
      diminuta showed that the haplotypes from Lanzarote and Fuerteventura are the most
      distant with respect to the other islands, but clearly related among them.
      CONCLUSIONS: Founder effects and biotic and abiotic factors could have played
      important role in the presence/absence of the hymenolepidid species in determined
      locations. The haplotypes from the eastern islands (Fuerteventura and Lanzarote)
      seem to have shared an ancestral haplotype very distant from the most frequent
      one that was found in the rest of the islands. Two colonization events or a
      single event with subsequent isolation and reduced gene flow between western
      central and eastern islands, have taken place in the Archipelago. The three
      tapeworms detected are zoonotic species, and their presence among rodents from
      this Archipelago suggests a potential health risk to human via environmental
      contamination in high risk areas. However, the relatively low prevalence of
      infestations detected and the focal distribution of some of these species on
      certain islands reduce the general transmission risk to human.

PMID- 21943097
TI  - Coat color dilution in mice because of inactivation of the melanoma antigen MART
      1.
AB  - Melanoma antigen recognized by T cells 1 (MART-1) is a melanoma-specific antigen,
      which has been thoroughly studied in the context of immunotherapy against
      malignant melanoma and which is found only in the pigment cell lineage. However,
      its exact function and involvement in pigmentation is not clearly understood.
      Melanoma antigen recognized by T cells 1 has been shown to interact with the
      melanosomal proteins Pmel17 and OA1. To understand the function of MART-1 in
      pigmentation, we developed a new knockout mouse model. Mice deficient in MART-1
      are viable, but loss of MART-1 leads to a coat color phenotype, with a reduction
      in total melanin content of the skin and hair. Lack of MART-1 did not affect
      localization of melanocyte-specific proteins nor maturation of Pmel17.
      Melanosomes of hair follicle melanocytes in MART-1 knockout mice displayed
      morphological abnormalities, which were exclusive to stage III and IV
      melanosomes. In conclusion, our results suggest that MART-1 is a pigmentation
      gene that is required for melanosome biogenesis and/or maintenance.

PMID- 21943099
TI  - Health-care seeking behaviour among persons with diabetes in Uganda: an interview
      study.
AB  - BACKGROUND: Healthcare-seeking behaviour in patients with diabetes mellitus (DM)
      has been investigated to a limited extent, and not in developing countries.
      Switches between different health sectors may interrupt glycaemic control,
      affecting health. The aim of the study was to explore healthcare-seeking
      behaviour, including use of complementary alternative medicine (CAM) and
      traditional healers, in Ugandans diagnosed with DM. Further, to study whether
      gender influenced healthcare-seeking behaviour. METHODS: This is a descriptive
      study with a snowball sample from a community in Uganda. Semi-structured
      interviews were held with 16 women and 8 men, aged 25-70. Data were analysed by
      qualitative content analysis. RESULTS: Healthcare was mainly sought among doctors
      and nurses in the professional sector because of severe symptoms related to DM
      and/or glycaemic control. Females more often focused on follow-up of DM and
      chronic pain in joints, while males described fewer problems. Among those who
      felt that healthcare had failed, most had turned to traditional healers in the
      folk sector for prescription of herbs or food supplements, more so in women than
      men. Males more often turned to private for-profit clinics while females more
      often used free governmental institutions. CONCLUSIONS: Healthcare was mainly
      sought from nurses and physicians in the professional sector and females used
      more free-of-charge governmental institutions. Perceived failure in health care
      to manage DM or related complications led many, particularly women, to seek
      alternative treatment from CAM practitioners in the folk sector. Living
      conditions, including healthcare organisation and gender, seemed to influence
      healthcare seeking, but further studies are needed.

PMID- 21943098
TI  - A chemically defined carrier for the delivery of human mesenchymal stem/stromal
      cells to skin wounds.
AB  - Skin has a remarkable capacity for regeneration, but age- and diabetes-related
      vascular problems lead to chronic non-healing wounds for many thousands of U.K.
      patients. There is a need for new therapeutic approaches to treat these resistant
      wounds. Donor mesenchymal stem/stromal cells (MSCs) have been shown to assist
      cutaneous wound healing by accelerating re-epithelialization. The aim of this
      work was to devise a low risk and convenient delivery method for transferring
      these cells to wound beds. Plasma polymerization was used to functionalize the
      surface of medical-grade silicone with acrylic acid. Cells attached well to these
      carriers, and culture for up to 3 days on the carriers did not significantly
      affect their phenotype or ability to support vascular tubule formation. These
      carriers were then used to transfer MSCs onto human dermis. Cell transfer was
      confirmed using an MTT assay to assess viable cell numbers and enhanced green
      fluorescent protein-labeled MSCs to demonstrate that the cells post-transfer
      attached to the dermis. We conclude that this synthetic carrier membrane is a
      promising approach for delivery of therapeutic MSCs and opens the way for future
      studies to evaluate its impact on repairing difficult skin wounds.

PMID- 21943100
TI  - Awareness and knowledge of sexually transmitted diseases (STDs) among school
      going adolescents in Europe: a systematic review of published literature.
AB  - BACKGROUND: Sexually transmitted diseases (STDs) are a major health problem
      affecting mostly young people, not only in developing, but also in developed
      countries.We conducted this systematic review to determine awareness and
      knowledge of school-going male and female adolescents in Europe of STDs and if
      possible, how they perceive their own risk of contracting an STD. Results of this
      review can help point out areas where STD risk communication for adolescents
      needs to be improved. METHODS: Using various combinations of the terms "STD",
      "HIV", "HPV", "Chlamydia", "Syphilis", "Gonorrhoea", "herpes", "hepatitis B",
      "knowledge", "awareness", and "adolescents", we searched for literature published
      in the PubMed database from 01.01.1990 up to 31.12.2010. Studies were selected if
      they reported on the awareness and/or knowledge of one or more STD among school
      attending adolescents in a European country and were published in English or
      German. Reference lists of selected publications were screened for further
      publications of interest. Information from included studies was systematically
      extracted and evaluated. RESULTS: A total of 15 studies were included in the
      review. All were cross-sectional surveys conducted among school-attending
      adolescents aged 13 to 20 years. Generally, awareness and knowledge varied among
      the adolescents depending on gender.Six STDs were focussed on in the studies
      included in the review, with awareness and knowledge being assessed in depth
      mainly for HIV/AIDS and HPV, and to some extent for chlamydia. For syphilis,
      gonorrhoea and herpes only awareness was assessed. Awareness was generally high
      for HIV/AIDS (above 90%) and low for HPV (range 5.4%-66%). Despite knowing that
      use of condoms helps protect against contracting an STD, some adolescents still
      regard condoms primarily as an interim method of contraception before using the
      pill. CONCLUSION: In general, the studies reported low levels of awareness and
      knowledge of sexually transmitted diseases, with the exception of HIV/AIDS.
      Although, as shown by some of the findings on condom use, knowledge does not
      always translate into behaviour change, adolescents' sex education is important
      for STD prevention, and the school setting plays an important role. Beyond
      HIV/AIDS, attention should be paid to infections such as chlamydia, gonorrhoea
      and syphilis.

PMID- 21943101
TI  - BRAF and RAS oncogenes regulate Rho GTPase pathways to mediate migration and
      invasion properties in human colon cancer cells: a comparative study.
AB  - BACKGROUND: Colorectal cancer is a common disease that involves genetic
      alterations, such as inactivation of tumour suppressor genes and activation of
      oncogenes. Among them are RAS and BRAF mutations, which rarely coexist in the
      same tumour. Individual members of the Rho (Ras homology) GTPases contribute with
      distinct roles in tumour cell morphology, invasion and metastasis. The aim of
      this study is to dissect cell migration and invasion pathways that are utilised
      by BRAFV600E as compared to KRASG12V and HRASG12V oncoproteins. In particular,
      the role of RhoA (Ras homolog gene family, member A), Rac1 (Ras-related C3
      botulinum toxin substrate 1) and Cdc42 (cell division cycle 42) in cancer
      progression induced by each of the three oncogenes is described. METHODS: Colon
      adenocarcinoma cells with endogenous as well as ectopically expressed or silenced
      oncogenic mutations of BRAFV600E, KRASG12V and HRASG12V were employed. Signalling
      pathways and Rho GTPases were inhibited with specific kinase inhibitors and
      siRNAs. Cell motility and invasion properties were correlated with cytoskeletal
      properties and Rho GTPase activities. RESULTS: Evidence presented here indicate
      that BRAFV600E significantly induces cell migration and invasion properties in
      vitro in colon cancer cells, at least in part through activation of RhoA GTPase.
      The relationship established between BRAFV600E and RhoA activation is mediated by
      the MEK-ERK pathway. In parallel, KRASG12V enhances the ability of colon
      adenocarcinoma cells Caco-2 to migrate and invade through filopodia formation and
      PI3K-dependent Cdc42 activation. Ultimately increased cell migration and
      invasion, mediated by Rac1, along with the mesenchymal morphology obtained
      through the Epithelial-Mesenchymal Transition (EMT) were the main characteristics
      rendered by HRASG12V in Caco-2 cells. Moreover, BRAF and KRAS oncogenes are shown
      to cooperate with the TGFbeta-1 pathway to provide cells with additional
      transforming properties. CONCLUSION: This study discriminates oncogene-specific
      cell migration and invasion pathways mediated by Rho GTPases in colon cancer
      cells and reveals potential new oncogene-specific characteristics for targeted
      therapeutics.

PMID- 21943102
TI  - Reasons for non- use of condoms and self- efficacy among female sex workers: a
      qualitative study in Nepal.
AB  - BACKGROUND: Heterosexual contact is the most common mode of transmission of
      sexually transmitted infections (STIs) including Human Immunodeficiency Virus
      (HIV) in Nepal and it is largely linked to sex work. We assessed the non-use of
      condoms in sex work with intimate sex partners by female sex workers (FSWs) and
      the associated self-efficacy to inform the planning of STI/HIV prevention
      programmes in the general population. METHODS: This paper is based on a
      qualitative study of Female Sex Workers (FSWs) in Nepal. In-depth interviews and
      extended field observation were conducted with 15 FSWs in order to explore issues
      of safe sex and risk management in relation to their work place, health and
      individual behaviours. RESULTS: The main risk factor identified for the non-use
      of condoms with intimate partners and regular clients was low self efficacy. Non
      use of condoms with husband and boyfriends placed them at risk of STIs including
      HIV. In addition to intimidation and violence from the police, clients and
      intimate partners, clients' resistance and lack of negotiation capacity were
      identified as barriers in using condoms by the FSWs. CONCLUSION: This study sheds
      light on the live and work of FSWs in Nepal. This information is relevant for
      both the Government of Nepal and Non Governmental Organisations (NGO) to help
      improve the position of FSWs in the community, their general well-being and to
      reduce their risks at work.

PMID- 21943103
TI  - Comparing social attention in autism and amygdala lesions: effects of stimulus
      and task condition.
AB  - The amygdala plays a critical role in orienting gaze and attention to socially
      salient stimuli. Previous work has demonstrated that SM a patient with rare
      bilateral amygdala lesions, fails to fixate and make use of information from the
      eyes in faces. Amygdala dysfunction has also been implicated as a contributing
      factor in autism spectrum disorders (ASD), consistent with some reports of
      reduced eye fixations in ASD. Yet, detailed comparisons between ASD and patients
      with amygdala lesions have not been undertaken. Here we carried out such a
      comparison, using eye tracking to complex social scenes that contained faces. We
      presented participants with three task conditions. In the Neutral task,
      participants had to determine what kind of room the scene took place in. In the
      Describe task, participants described the scene. In the Social Attention task,
      participants inferred where people in the scene were directing their attention.
      SM spent less time looking at the eyes and much more time looking at the mouths
      than control subjects, consistent with earlier findings. There was also a trend
      for the ASD group to spend less time on the eyes, although this depended on the
      particular image and task. Whereas controls and SM looked more at the eyes when
      the task required social attention, the ASD group did not. This pattern of
      impairments suggests that SM looks less at the eyes because of a failure in
      stimulus-driven attention to social features, whereas individuals with ASD look
      less at the eyes because they are generally insensitive to socially relevant
      information and fail to modulate attention as a function of task demands. We
      conclude that the source of the social attention impairment in ASD may arise
      upstream from the amygdala, rather than in the amygdala itself.

PMID- 21943105
TI  - Efficacy of electroacupuncture at Zhongliao point (BL33) for mild and moderate
      benign prostatic hyperplasia: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Acu-point specificity is a key issue in acupuncture. To date there
      has not been any satisfactory trial which can ratify the specific effect of
      acupuncture. This trial will evaluate the specific effect of BL33 for mild and
      moderate benign prostatic hyperplasia (BPH) on the basis of its effectiveness.
      The non-specific effect will be excluded and the therapeutic effect will be
      evaluated. METHOD: This is a double-blinded randomized controlled trial. 100
      Patients will be randomly allocated into the treatment group (n = 50) and the
      control group (n = 50). The treatment group receives needling at BL33 and the
      control group receives needling at non-point. The needling depth, angle,
      direction, achievement of De Qi and parameters of electroacupuncture are exactly
      the same in both groups. The primary outcome measure is reduction of
      international prostate symptom score (IPSS) at the 6th week and the secondary
      outcome measures are reduction of bladder residual urine, increase in maximum
      urinary flow rate at the 6th week and reduction of IPSS at the 18th week.
      DISCUSSION: This trial will assess the specific therapeutic effect of
      electroacupuncture at BL33 for mild and moderate BPH. TRIAL REGISTRATION:
      Protocol Registration System of Clinical Trials.gov NCT01218243.

PMID- 21943104
TI  - Extracellular ATP activates NFAT-dependent gene expression in neuronal PC12 cells
      via P2X receptors.
AB  - BACKGROUND: Treatment of neuronal PC12 cells with ATP induces depolarisation and
      increases intracellular calcium levels via purinergic receptors. In many cell
      types, sustained elevation of intracellular calcium levels cause changes in gene
      expression via activation of the transcription factor NFAT (nuclear factor of
      activated T cells). We have therefore characterised the signalling pathway by
      which ATP regulates NFAT-dependent gene expression in PC12 cells. RESULTS: The
      activation of NFAT transcriptional activity by extracellular ATP was
      characterised with the help of reporter gene assays. Treatment of PC12 cells with
      ATP elicited a dose-dependent increase in luciferase activity (EC50 = 78 MUM).
      UTP, 4-benzoylbenzoyl ATP and alpha,beta-methylene ATP did not mimic the effect
      of ATP, which was abolished by treatment with the P2X receptor antagonist
      pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate (PPADS). This pharmacological
      characterisation provides evidence for a critical role of ionotropic P2X
      receptors. Blockade of L-type voltage-dependent calcium channels by nifedipine
      reduced the response of NFAT to ATP, indicating that a depolarisation-mediated
      calcium influx was required for maximal NFAT activation. Inhibition of store
      operated calcium entry by the pyrazole derivative BTP2 also diminished ATP
      dependent NFAT activation. Furthermore, ATP-induced NFAT activation was
      associated with the activation of the mitogen-activated protein kinases ERK1/2.
      Finally, treatment with ATP increased the levels of the NFAT target transcripts,
      RCAN1-4 (regulator of calcineurin) and BDNF (brain derived neurotrophic factor).
      CONCLUSION: The present data show that ATP induces NFAT-dependent changes in gene
      expression in PC12 cells by acting on P2X receptors. Maximal NFAT activation
      depends on both depolarisation-induced calcium influx and store-operated calcium
      entry and requires the activity of the protein phosphatase calcineurin and the
      mitogen-activated protein kinase cascade.

PMID- 21943106
TI  - Y-chromosome phylogeny in the evolutionary net of chamois (genus Rupicapra).
AB  - BACKGROUND: The chamois, distributed over most of the medium to high altitude
      mountain ranges of southern Eurasia, provides an excellent model for exploring
      the effects of historical and evolutionary events on diversification. Populations
      have been grouped into two species, Rupicapra pyrenaica from southwestern Europe
      and R. rupicapra from eastern Europe. The study of matrilineal mitochondrial DNA
      (mtDNA) and biparentally inherited microsatellites showed that the two species
      are paraphyletic and indicated alternate events of population contraction and
      dispersal-hybridization in the diversification of chamois. Here we investigate
      the pattern of variation of the Y-chromosome to obtain information on the
      patrilineal phylogenetic position of the genus Rupicapra and on the male-specific
      dispersal of chamois across Europe. RESULTS: We analyzed the Y-chromosome of 87
      males covering the distribution range of the Rupicapra genus. We sequenced a
      fragment of the SRY gene promoter and characterized the male specific
      microsatellites UMN2303 and SRYM18. The SRY promoter sequences of two samples of
      Barbary sheep (Ammotragus lervia) were also determined and compared with the
      sequences of Bovidae available in the GenBank. Phylogenetic analysis of the
      alignment showed the clustering of Rupicapra with Capra and the Ammotragus
      sequence obtained in this study, different from the previously reported sequence
      of Ammotragus which groups with Ovis. Within Rupicapra, the combined data define
      10 Y-chromosome haplotypes forming two haplogroups, which concur with taxonomic
      classification, instead of the three clades formed for mtDNA and nuclear
      microsatellites. The variation shows a west-to-east geographical cline of
      ancestral to derived alleles. CONCLUSIONS: The phylogeny of the SRY-promoter
      shows an association between Rupicapra and Capra. The position of Ammotragus
      needs a reinvestigation. The study of ancestral and derived characters in the Y
      chromosome suggests that, contrary to the presumed Asian origin, the paternal
      lineage of chamois originated in the Mediterranean, most probably in the Iberian
      Peninsula, and dispersed eastwards through serial funding events during the
      glacial-interglacial cycles of the Quaternary. The diversity of Y-chromosomes in
      chamois is very low. The differences in patterns of variation among Y-chromosome,
      mtDNA and biparental microsatellites reflect the evolutionary characteristics of
      the different markers as well as the effects of sex-biased dispersal and species
      phylogeography.

PMID- 21943107
TI  - Determinants of insecticide treated nets use among youth corp members in Edo
      State, Nigeria.
AB  - BACKGROUND: The Africa Malaria Report shows that many countries are quite far
      from reaching the universal coverage targets of 80% coverage by 2010 and maintain
      it at this level. This paper examines ITN use and the factors associated with its
      adoption among the youths in Nigeria. This information will help in the design of
      effective methods of providing and distributing the nets in order to enhance its
      adoption and maximize the public health benefits of ITNs. METHODS: This cross
      sectional survey was carried out in 2006 among university leavers serving
      compulsory national service (youth corpers) using total sampling technique. The
      study was conducted using a self-administered questionnaire. RESULTS: A total of
      656 youth corp members were interviewed. Only 23.8% of these youths ever use ITN
      while 4.3% currently use ITN before reporting in camp. A significant proportion
      of the youths acquired information on ITN from Mass Media (p = 0.0001). Other
      statistically significant factors that encourage the use of ITN include
      inexpensive market price of ITN (p = 0.0001), frequency of Malaria infestation (p
      = 0.019) and perceived malaria preventive action of ITN ( p = 0.000).Following
      logistic regression analysis, perceived effective malaria preventive action of
      ITN [OR = 29.3, C.I = 17.17-50.0] and high frequency of Malaria infestation [OR =
      1.55, C.I = 0.97-2.47] were predictors of ITN use. CONCLUSION: The study shows
      that the use of ITN for the prevention of Malaria is low among these Nigerian
      youths. The major factors determining the adoption of ITN among the youths were
      perceived effective Malaria prevention action of ITN and high frequency of
      Malaria attack. These factors should be considered in the design of sustainable
      and effective locally relevant strategies for scale-up adoption of ITNs among a
      youthful African population.

PMID- 21943108
TI  - A novel angiopoietin-derived peptide displays anti-angiogenic activity and
      inhibits tumour-induced and retinal neovascularization.
AB  - BACKGROUND AND PURPOSE: Pathological angiogenesis is associated with various
      human diseases, such as cancer, autoimmune diseases and retinopathy. The
      angiopoietin (Ang)-Tie2 system plays critical roles in several steps of
      angiogenic remodelling. Here, we have investigated the anti-angiogenic effect of
      a novel angiopoietin-derived peptide. EXPERIMENTAL APPROACH: Using computational
      methods, we identified peptides from helical segments within angiopoietins, which
      were predicted to inhibit their activity. These peptides were tested using
      biochemical methods and models of angiogenesis. The peptide with best efficacy,
      A11, was selected for further characterization as an anti-angiogenic compound.
      KEY RESULTS: The potent anti-angiogenic activity of A11 was demonstrated in a
      multicellular assay of angiogenesis and in the chorioallantoic membrane model.
      A11 bound to angiopoietins and reduced the binding of Ang-2 to Tie2. A11 was also
      significantly reduced vascular density in a model of tumour-induced angiogenesis.
      Its ability to inhibit Ang-2 but not Ang-1-induced endothelial cell migration,
      and to down-regulate Tie2 levels in tumour microvessels, suggests that A11
      targets the Ang-Tie2 pathway. In a rat model of oxygen-induced retinopathy, A11
      strongly inhibited retinal angiogenesis. Moreover, combination of A11 with an
      anti-VEGF antibody showed a trend for further inhibition of angiogenesis,
      suggesting an additive effect. CONCLUSIONS AND IMPLICATIONS: Our results indicate
      that A11 is a potent anti-angiogenic compound, through modulation of the Ang-Tie2
      system, underlining its potential as a therapeutic agent for the treatment of
      ocular and tumour neovascularization, as well as other pathological conditions
      that are dependent on angiogenesis.

PMID- 21943109
TI  - Hydroxychavicol, a Piper betle leaf component, induces apoptosis of CML cells
      through mitochondrial reactive oxygen species-dependent JNK and endothelial
      nitric oxide synthase activation and overrides imatinib resistance.
AB  - Alcoholic extract of Piper betle (Piper betle L.) leaves was recently found to
      induce apoptosis of CML cells expressing wild type and mutated Bcr-Abl with
      imatinib resistance phenotype. Hydroxy-chavicol (HCH), a constituent of the
      alcoholic extract of Piper betle leaves, was evaluated for anti-CML activity.
      Here, we report that HCH and its analogues induce killing of primary cells in CML
      patients and leukemic cell lines expressing wild type and mutated Bcr-Abl,
      including the T315I mutation, with minimal toxicity to normal human peripheral
      blood mononuclear cells. HCH causes early but transient increase of mitochondria
      derived reactive oxygen species. Reactive oxygen species-dependent persistent
      activation of JNK leads to an increase in endothelial nitric oxide synthase
      mediated nitric oxide generation. This causes loss of mitochondrial membrane
      potential, release of cytochrome c from mitochondria, cleavage of caspase 9, 3
      and poly-adenosine diphosphate-ribose polymerase leading to apoptosis. One HCH
      analogue was also effective in vivo in SCID mice against grafts expressing the
      T315I mutation, although to a lesser extent than grafts expressing wild type Bcr
      Abl, without showing significant bodyweight loss. Our data describe the role of
      JNK-dependent endothelial nitric oxide synthase-mediated nitric oxide for anti
      CML activity of HCH and this molecule merits further testing in pre-clinical and
      clinical settings.

PMID- 21943110
TI  - Toll-like receptor activation by helminths or helminth products to alleviate
      inflammatory bowel disease.
AB  - Helminth infection may modulate the expression of Toll like receptors (TLR) in
      dendritic cells (DCs) and modify the responsiveness of DCs to TLR ligands. This
      may regulate aberrant intestinal inflammation in humans with helminthes and may
      thus help alleviate inflammation associated with human inflammatory bowel disease
      (IBD). Epidemiological and experimental data provide further evidence that
      reducing helminth infections increases the incidence rate of such autoimmune
      diseases. Fine control of inflammation in the TLR pathway is highly desirable for
      effective host defense. Thus, the use of antagonists of TLR-signaling and
      agonists of their negative regulators from helminths or helminth products should
      be considered for the treatment of IBD.

PMID- 21943111
TI  - Restrictive strategy of intraoperative fluid maintenance during optimization of
      oxygen delivery decreases major complications after high-risk surgery.
AB  - INTRODUCTION: Optimal fluid management is crucial for patients who undergo major
      and prolonged surgery. Persistent hypovolemia is associated with complications,
      but fluid overload is also harmful. We evaluated the effects of a restrictive
      versus conventional strategy of crystalloid administration during goal-directed
      therapy in high-risk surgical patients. METHODS: We conducted a prospective,
      randomized, controlled study of high-risk patients undergoing major surgery. For
      fluid maintenance during surgery, the restrictive group received 4 ml/kg/hour and
      the conventional group received 12 ml/kg/hour of Ringer's lactate solution. A
      minimally invasive technique (the LiDCO monitoring system) was used to
      continuously monitor stroke volume and oxygen delivery index (DO2I) in both
      groups. Dobutamine was administered as necessary, and fluid challenges were used
      to test fluid responsiveness to achieve the best possible DO2I during surgery and
      for 8 hours postoperatively. RESULTS: Eighty-eight patients were included. The
      patients' median age was 69 years. The conventional treatment group received a
      significantly greater amount of lactated Ringer's solution (mean +/- standard
      deviation (SD): 4, 335 +/- 1, 546 ml) than the restrictive group (mean +/- SD: 2,
      301 +/- 1, 064 ml) (P < 0.001). Temporal patterns of DO2I were similar between
      the two groups. The restrictive group had a 52% lower rate of major postoperative
      complications than the conventional group (20.0% vs 41.9%, relative risk = 0.48,
      95% confidence interval = 0.24 to 0.94; P = 0.046). CONCLUSIONS: A restrictive
      strategy of fluid maintenance during optimization of oxygen delivery reduces
      major complications in older patients with coexistent pathologies who undergo
      major surgery. TRIAL REGISTRATION: ISRCTN: ISRCTN94984995.

PMID- 21943113
TI  - Principal component and factor analytic models in international sire evaluation.
AB  - BACKGROUND: Interbull is a non-profit organization that provides internationally
      comparable breeding values for globalized dairy cattle breeding programmes. Due
      to different trait definitions and models for genetic evaluation between
      countries, each biological trait is treated as a different trait in each of the
      participating countries. This yields a genetic covariance matrix of dimension
      equal to the number of countries which typically involves high genetic
      correlations between countries. This gives rise to several problems such as over
      parameterized models and increased sampling variances, if genetic (co)variance
      matrices are considered to be unstructured. METHODS: Principal component (PC) and
      factor analytic (FA) models allow highly parsimonious representations of the
      (co)variance matrix compared to the standard multi-trait model and have,
      therefore, attracted considerable interest for their potential to ease the burden
      of the estimation process for multiple-trait across country evaluation (MACE).
      This study evaluated the utility of PC and FA models to estimate variance
      components and to predict breeding values for MACE for protein yield. This was
      tested using a dataset comprising Holstein bull evaluations obtained in 2007 from
      25 countries. RESULTS: In total, 19 principal components or nine factors were
      needed to explain the genetic variation in the test dataset. Estimates of the
      genetic parameters under the optimal fit were almost identical for the two
      approaches. Furthermore, the results were in a good agreement with those obtained
      from the full rank model and with those provided by Interbull. The estimation
      time was shortest for models fitting the optimal number of parameters and
      prolonged when under- or over-parameterized models were applied. Correlations
      between estimated breeding values (EBV) from the PC19 and PC25 were unity. With
      few exceptions, correlations between EBV obtained using FA and PC approaches
      under the optimal fit were >= 0.99. For both approaches, EBV correlations
      decreased when the optimal model and models fitting too few parameters were
      compared. CONCLUSIONS: Genetic parameters from the PC and FA approaches were very
      similar when the optimal number of principal components or factors was fitted.
      Over-fitting increased estimation time and standard errors of the estimates but
      did not affect the estimates of genetic correlations or the predictions of
      breeding values, whereas fitting too few parameters affected bull rankings in
      different countries.

PMID- 21943114
TI  - Inflammatory pseudotumors of the kidney and the lung presenting as immunoglobulin
      G4-related disease: a case report.
AB  - INTRODUCTION: It has been reported that immunoglobulin G4-related systemic
      disease can spread to nearly every organ, and often presents as an inflammatory
      mass or masses at those sites. In the kidney, this disease is often diagnosed
      after a radical or partial nephrectomy following the discovery of an inflammatory
      mass which is often suspected to be a malignant tumor. Here, we present a rare
      case of inflammatory pseudotumors of the kidney and the lung presenting as
      immunoglobulin G4-related disease, which were diagnosed by computed tomography
      guided biopsies. CASE PRESENTATION: A 54-year-old Japanese man was referred to
      our hospital with suspected bilateral renal cancer, multiple lung metastases and
      autoimmune pancreatitis. His serum immunoglobulin G4 level was high. We used
      computed tomography-guided biopsies and histopathological examinations of the
      biopsied specimens to diagnose the tumors as immunoglobulin G4-related bilateral
      renal and lung inflammatory pseudotumors. Our patient was treated with oral
      prednisolone, and after one month of treatment, contrast-enhanced computed
      tomography demonstrated a general improvement, as noted by a reduction in size of
      the masses. CONCLUSION: Renal masses that are formed due to immunoglobulin G4
      related disease require comprehensive diagnosis to prevent unnecessary surgical
      resections from being performed. Further consideration should be paid to
      immunoglobulin G4-related diseases in the future.

PMID- 21943112
TI  - Association of ADIPOR2 gene variants with cardiovascular disease and type 2
      diabetes risk in individuals with impaired glucose tolerance: the Finnish
      Diabetes Prevention Study.
AB  - BACKGROUND: Adiponectin is an adipokine with insulin-sensitising and anti
      atherogenic effects. Two receptors for adiponectin, ADIPOR1 and ADIPOR2, have
      been characterized that mediate effects of adiponectin in various tissues. We
      examined whether genetic variation in ADIPOR2 predicts the development of
      cardiovascular disease (CVD) and/or Type 2 Diabetes (T2DM) in individuals with
      impaired glucose tolerance (IGT) participating the Finnish Diabetes Prevention
      Study (DPS). METHODS: CVD morbidity and mortality data were collected during a
      median follow-up of 10.2 years (range 1-13 years) and conversion from IGT to T2DM
      was assessed during a median follow-up of 7 years (range 1-11 years). Altogether
      eight SNPs in the ADIPOR2 locus were genotyped in 484 participants of the DPS.
      Moreover, the same SNPs were genotyped and the mRNA expression levels of ADIPOR2
      were determined in peripheral blood mononuclear cells and subcutaneous adipose
      tissue samples derived from 56 individuals participating in the Genobin study.
      RESULTS: In the DPS population, four SNPs (rs10848554, rs11061937, rs1058322,
      rs16928751) were associated with CVD risk, and two remained significant (p =
      0.014 for rs11061937 and p = 0.020 for rs1058322) when all four were included in
      the same multi-SNP model. Furthermore, the individuals homozygous for the rare
      minor alleles of rs11061946 and rs11061973 had increased risk of converting from
      IGT to T2DM. Allele-specific differences in the mRNA expression levels for the
      rs1058322 variant were seen in peripheral blood mononuclear cells derived from
      participants of the Genobin study. CONCLUSIONS: Our results suggest that SNPs in
      the ADIPOR2 may modify the risk of CVD in individuals with IGT, possibly through
      alterations in the mRNA expression levels. In addition an independent genetic
      signal in ADIPOR2 locus may have an impact on the risk of developing T2DM in
      individuals with IGT. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT00518167.

PMID- 21943115
TI  - First-line antiretroviral therapy and dyslipidemia in people living with HIV-1 in
      Cameroon: a cross-sectional study.
AB  - BACKGROUND: Data on lipid profile derangements induced by antiretroviral
      treatment in Africa are scarce. The aim of this study was to determine the
      prevalence and characteristics of lipid profile derangements associated with
      first-line highly active antiretroviral therapy (ART) among Cameroonians living
      with human immunodeficiency virus (HIV) infection. METHODS: This cross-sectional
      study was conducted between November 2009 and January 2010, and involved 138 HIV
      patients who had never received ART (ART-naive group) and 138 others treated for
      at least 12 months with first line triple ART regimens that included nevirapine
      or efavirenz (ART group). Lipid profile was determined after overnight fast and
      dyslipidemia diagnosed according to the US National Cholesterol Education Program
      III criteria. Data comparison used chi-square test, Student t-test and logistic
      regressions. RESULTS: The prevalence of total cholesterol >= 200 mg/dl was 37.6%
      and 24.6% respectively in ART group and ART-naive groups (p = 0.019). The
      equivalents for LDL-cholesterol >= 130 mg/dl were 46.4% and 21% (p <= 0.001).
      Proportions of patients with total cholesterol/HDL-cholesterol ratio >= 5 was
      35.5% in ART group and 18.6% in ART-naive group (p <= 0.001). The distribution of
      HDL-cholesterol and triglycerides was similar between the two groups. In
      multivariable analysis adjusted for age, sex, body mass index, CD4 count and co
      infection with tuberculosis, being on ART was significantly and positively
      associated with raised total cholesterol, LDL-cholesterol and TC/HDL cholesterol.
      The adjusted odd ratios (95% confidence interval, p-value) ART-treated vs. ART
      naive was 1.82 (1.06-1.12, p = 0.02) for TC >= 200 mg/dl; 2.99 (1.74-5.15), p <
      0.0001) for LDL-cholesterol >= 130 mg/dl and 1.73 (1.04-2.89, p = 0.03) for
      TC/HDL-cholesterol >= 5. CONCLUSIONS: First-line antiretroviral therapy that
      includes nonnucleoside reverse transcriptase inhibitors is associated with pro
      atherogenic adverse lipid profile in people with HIV-1 infection compared to
      untreated HIV-infected subjects in Yaounde. Lipid profile and other
      cardiovascular risk factors should be monitored in patients on such therapy so
      that any untoward effects of treatments can be optimally managed.

PMID- 21943116
TI  - Total thoracoscopic lung segmentectomy of anterior basal segment of the right
      lower lobe (RS8) for NSCLC stage IA (case report).
AB  - A 69-year-old woman with a pulmonary nodule in anterior basal segment of the
      right lower lobe (RS8) was referred to our department. The diameter of the tumor
      was 12 mm, and it had increased over a few months. First, video-assisted
      thoracoscopic lung surgery (VATS) biopsy of the pulmonary nodule was carried out.
      Frozen section examination of this nodule confirmed the diagnosis of
      bronchioloalveolar carcinoma (BAC). Segmentectomy of RS8 with lower mediastinal
      node dissection (ND2a-1) was performed. The intersegmental plane was identified
      using the intersegmental veins as landmarks and the demarcation between the
      resected (inflated) and preserved (collapsed) lungs. Electrocautery at 70 watts
      was used to divide the intersegmental plane. A vessel sealing system was used to
      seal and cut the pulmonary arteries. Postoperative histopathological examination
      revealed that the tumor was T1aN0M0 BAC, and the minimal distance between the
      surgical margin and the tumor edge was 15 mm. The patient was discharged from
      hospital on postoperative day 5 without any complications.

PMID- 21943118
TI  - Electronic paper display preferred viewing distance and character size for
      different age groups.
AB  - This study explores the preferred viewing distance and character size for an
      electronic paper display for three age groups. Proofreading speed and accuracy
      ratio were measured during Chinese proofreading tests using the preferred
      character size and minimum acceptable character size. Data analysis showed that
      the mean preferred viewing distance for young, middle-aged and older groups was
      503, 455 and 444 mm, respectively. The mean preferred character size determined
      by young, middle-aged and older groups was 42.0, 50.0 and 55.2 min arc,
      respectively. The proofreading test results indicated that the older group
      proofread significantly more slowly (1.25 word/sec) than the young (1.76
      word/sec) and middle-aged groups (1.74 word/sec). Further, the participants
      proofread more correctly with their preferred character size (73.3%) than with
      their minimum acceptable character size (65.4%). This study provides valuable
      information for the design of Chinese text presentations for various age groups.
      STATEMENT OF RELEVANCE: This study confirmed the preferred viewing distance and
      character size for E-paper display were influenced by age. The preferred Chinese
      character size for young, middle-aged and older people was 42, 50 and 55 min arc,
      respectively. Therefore, the age factor should be considered for E-paper displays
      design and video display terminal (VDT) guidelines.

PMID- 21943117
TI  - Decreased expression of dual-specificity phosphatase 9 is associated with poor
      prognosis in clear cell renal cell carcinoma.
AB  - BACKGROUND: The molecular mechanisms involved in the development and progression
      of clear cell renal cell carcinomas (ccRCCs) are poorly understood. The objective
      of this study was to analyze the expression of dual-specificity phosphatase 9
      (DUSP-9) and determine its clinical significance in human ccRCCs. METHODS: The
      expression of DUSP-9 mRNA was determined in 46 paired samples of ccRCCs and
      adjacent normal tissues by using real-time qPCR. The expression of the DUSP-9 was
      determined in 211 samples of ccRCCs and 107 paired samples of adjacent normal
      tissues by immunohistochemical analysis. Statistical analysis was performed to
      define the relationship between the expression of DUSP-9 and the clinical
      features of ccRCC. RESULTS: The mRNA level of DUSP-9, which was determined by
      real-time RT-PCR, was found to be significantly lower in tumorous tissues than in
      the adjacent non-tumorous tissues (p < 0.001). An immunohistochemical analysis of
      107 paired tissue specimens showed that the DUSP-9 expression was lower in
      tumorous tissues than in the adjacent non-tumorous tissues (p < 0.001). Moreover,
      there was a significant correlation between the DUSP-9 expression in ccRCCs and
      gender (p = 0.031), tumor size (p = 0.001), pathologic stage (p = 0.001), Fuhrman
      grade (p = 0.002), T stage (p = 0.001), N classification (p = 0.012), metastasis
      (p = 0.005), and recurrence (p < 0.001). Patients with lower DUSP-9 expression
      had shorter overall survival time than those with higher DUSP-9 expression (p <
      0.001). Multivariate analysis indicated that low expression of the DUSP-9 was an
      independent predictor for poor survival of ccRCC patients. CONCLUSION: To our
      knowledge, this is the first study that determines the relationship between DUSP
      9 expression and prognosis in ccRCC. We found that decreased expression of DUSP-9
      is associated with poor prognosis in ccRCC. DUSP-9 may represent a novel and
      useful prognostic marker for ccRCC.

PMID- 21943119
TI  - Evaluation of upper-limb body postures based on the effects of back and shoulder
      flexion angles on subjective discomfort ratings, heart rates and muscle
      activities.
AB  - A possible limitation of many ergonomics checklists that evaluate postures is an
      independent evaluation of each body segment without considering the coordination
      between body segments and resulting in the under-/over-estimation of body
      postures. A total of 20 men were selected to evaluate the effects of shoulder and
      back flexion angles on the upper-limb muscle activities, subjective discomforts
      and heart rates. Interesting findings were obtained from the coordination between
      back flexion angles and shoulder flexion angles. At a back flexion angle of 45
      degrees , the discomfort and heart rates were the least at a shoulder flexion
      angle of 45 degrees . The %MVC also showed a similar trend. It could be inferred
      that the 0 degrees  shoulder flexion angle would be a natural posture, when the
      back flexion angle is 0 degrees , whereas 45 degrees  shoulder flexion might be a
      more natural posture when the back flexion angle is 45 degrees . STATEMENT OF
      RELEVANCE: This study evaluated the effects of back and shoulder flexion angles
      on subjective as well as objective measures. The findings of this study
      considered the coordination between two body flexion angles and could be used to
      improve the accuracy of existing ergonomics evaluation methods for body postures.

PMID- 21943120
TI  - Cumulative postural exposure measured by a novel device: a preliminary study.
AB  - The aim of the present study was to examine the within-day reliability of the
      Spineangel(r) postural monitoring device and to measure cumulative lumbo-pelvic
      posture exposure of health care workers. Twenty-one workers from an aged-care
      residential home wore the Spineangel, attached to the belt or waistband of their
      normal work apparel, during a period of the work shift. To assess the within-day
      reliability of measurements, 11 workers performed two sets of three lumbo-pelvic
      forward flexion, sustaining them for five 5 s each, at the beginning and at the
      end of the work shift. Different thresholds for cumulative postural exposure were
      measured. The reliability was found to be excellent (ICC = 0.81). On average, a
      threshold of 30 degrees  of lumbo-pelvic forward flexion was exceeded 1069
      times/h (SD 2157.1); at 45 degrees , 121 times/h (SD 223.8); and at 60 degrees ,
      8 times/h (SD 21.8). The use of Spineangel is thus likely to be a useful device
      for monitoring work posture. STATEMENT OF RELEVANCE: The Spineangel(r) is capable
      of providing reliable postural measurements in the workplace. Different
      cumulative postural exposure thresholds were established considering three
      domains of cumulative exposure: magnitude (range of motion), frequency and
      duration. The implementation of such domains for cumulative exposure allowed us
      to explore interesting forms of monitoring posture exposure.

PMID- 21943121
TI  - Physical restraint in mental health services: a gap in the knowledge regarding
      this extreme manual handling task.

PMID- 21943122
TI  - Transglutaminase 2 as an independent prognostic marker for survival of patients
      with non-adenocarcinoma subtype of non-small cell lung cancer.
AB  - BACKGROUND: Expression of transglutaminase 2 (TGase 2) is related to invasion and
      resistance to chemotherapeutic agents in several cancer cells. However, there has
      been only limited clinical validation of TGase 2 as an independent prognostic
      marker in cancer. METHODS: The significance of TGase 2 expression as an
      invasive/migratory factor was addressed by in vitro assays employing down
      regulation of TGase 2. TGase 2 expression as a prognostic indicator was assessed
      in 429 Korean patients with early-stage non-small cell lung cancer (NSCLC) by
      immunohistochemical staining. RESULTS: TGase 2 expression increased the invasive
      and migratory properties of NSCLC cells in vitro, which might be related to the
      induction of MMP-9. In the analysis of the immunohistochemical staining, TGase 2
      expression in tumors was significantly correlated with recurrence in NSCLC (p =
      0.005) or in the non-adenocarcinoma subtype (p = 0.031). Additionally, a
      multivariate analysis also showed a significant correlation between strong TGase
      2 expression and shorter disease-free survival (DFS) in NSCLC (p = 0.029 and HR =
      1.554) and in the non-adenocarcinoma subtype (p = 0.030 and HR = 2.184). However,
      the correlation in the adenocarcinoma subtype was not significant. CONCLUSIONS:
      TGase 2 expression was significantly correlated with recurrence and shorter DFS
      in NSCLC, especially in the non-adenocarcinoma subtype including squamous cell
      carcinoma.

PMID- 21943123
TI  - BACE1 inhibitory activity of fungal endophytic extracts from Malaysian medicinal
      plants.
AB  - BACKGROUND: BACE1 was found to be the major beta-secretase in neurons and its
      appearance and activity were found to be elevated in the brains of AD patients.
      Fungal endophytic extracts for BACE1 inhibitory activity and cytotoxicity against
      PC-12 (a rat pheochromocytoma with neuronal properties) and WRL68 (a non
      tumorigenic human hepatic) were investigated. METHODS: Endophytes were isolated
      from plants collected from Kuala Pilah, Negeri Sembilan and the National Park,
      Pahang and the extracts were tested for BACE1 inhibition. For investigation of
      biological activity, the pure endophytic cultures were cultivated for 14 days on
      PDA plates at 28 degrees C and underwent semipolar extraction with ethyl acetate.
      RESULTS: Of 212 endophytic extracts (1000 MUg/ml), 29 exhibited more than 90%
      inhibition of BACE1 in the preliminary screening. Four extracts from isolates
      HAB16R13, HAB16R14, HAB16R18 and HAB8R24 identified as Cytospora rhizophorae were
      the most active with IC(50(BACE1)) values of less than 3.0 MUg/ml. The most
      active extract HAB16R13 was shown to non-competitively inhibit BACE1 with K(i)
      value of 10.0 MUg/ml. HAB16R13 was considered non-potent against PC-12 and WRL68
      (IC(50(CT))) of 60.0 and 40.0 MUg/ml, respectively). CONCLUSIONS: This first
      report on endophytic fungal extract with good BACE1 inhibitory activity
      demonstrates that more extensive study is required to uncover the potential of
      endophytes.

PMID- 21943124
TI  - A deletion of FGFR2 creating a chimeric IIIb/IIIc exon in a child with Apert
      syndrome.
AB  - BACKGROUND: Signalling by fibroblast growth factor receptor type 2 (FGFR2)
      normally involves a tissue-specific alternative splice choice between two exons
      (IIIb and IIIc), which generates two receptor isoforms (FGFR2b and FGFR2c
      respectively) with differing repertoires of FGF-binding specificity. Here we
      describe a unique chimeric IIIb/c exon in a patient with Apert syndrome,
      generated by a non-allelic homologous recombination event. CASE PRESENTATION: We
      present a child with Apert syndrome in whom routine genetic testing had excluded
      the FGFR2 missense mutations commonly associated with this disorder. The patient
      was found to harbour a heterozygous 1372 bp deletion between FGFR2 exons IIIb and
      IIIc, apparently originating from recombination between 13 bp of identical DNA
      sequence present in both exons. The rearrangement was not present in the
      unaffected parents. CONCLUSIONS: Based on the known pathogenesis of Apert
      syndrome, the chimeric FGFR2 protein is predicted to act in a dominant gain-of
      function manner. This is likely to result from its expression in mesenchymal
      tissues, where retention of most of the residues essential for FGFR2b binding
      activity would result in autocrine activation. This report adds to the repertoire
      of rare cases of Apert syndrome for which a pathogenesis based on atypical FGFR2
      rearrangements can be demonstrated.

PMID- 21943125
TI  - The structure of the atrioventricular node in the heart of the female laying
      ostrich (Struthio camelus).
AB  - The electrical impulse for cardiac contraction is generated in the Sinoatrial
      node (SA node), subsequently spreads to the Atrioventricular node (AV node) and
      continues in the Atrioventricular bundle (AV bundle). The AV node may not always
      be present in different avian species and seems to differ in location and
      contents between species. In this study, the anatomy and histology of the AV node
      were studied five female adult ostriches (Struthio camelus). Routine paraffin
      sectioning and transmission electron microscopic method were performed. The study
      showed that in the ostrich, the AV node is located in the endocardium of the
      atrial surface of the right atrioventricular valve adjacent to the fibrous ring.
      The parenchyma of the AV node is formed by small specialized muscle fibres that
      are spread within a loose connective tissue network. The AV node is not covered
      by a connective tissue sheath and some arterioles are present. Nerve fibres are
      seen related to the node. Ultrastructurally, they stain lighter and contain fewer
      organized myofibrils than usual myocardial cells. The myofibril bundles run
      parallel to one another and have interspersed mitochondria, which display
      distinct cristae. The cells have a large euchromatic nucleus with a clear
      perinuclear area, and they connected by desmosomes. The ostrich is, thus, one of
      the birds that have the AV node, whose position varies from the other birds.

PMID- 21943127
TI  - Social impairment in schizophrenia revealed by Autism-Spectrum Quotient
      correlated with gray matter reduction.
AB  - One of the difficulties facing schizophrenia patients is a failure to construct
      appropriate relationships with others in social situations. This impairment of
      social cognition is also found in autism-spectrum disorder (ASD). Considering
      such commonality between the two disorders, in this study we adopted the Autism
      Spectrum Quotient (AQ) score to assess autistic traits, and explored the
      association between such traits and gray matter (GM) alterations of the brain in
      schizophrenia. Twenty schizophrenia patients and 25 healthy controls underwent
      structural magnetic resonance imaging (MRI), and AQ was assessed, comprising five
      subscales measuring different facets of autistic traits. Voxel-based morphometry
      (VBM) was applied to investigate the correlation between these AQ scores and
      regional GM alterations. Schizophrenia patients showed significantly higher
      scores in total AQ, and in four of the five subscales, compared to healthy
      controls. The total AQ score in schizophrenia showed significant negative
      correlation with GM volume reduction in the cortical area surrounding the left
      superior temporal sulcus (STS), which is considered to be important in social
      perception. Our findings suggest a possible neuroanatomical basis of autistic
      tendencies in schizophrenia.

PMID- 21943126
TI  - A comparison of in vitro properties of resting SOD1 transgenic microglia reveals
      evidence of reduced neuroprotective function.
AB  - BACKGROUND: Overexpression of mutant copper/zinc superoxide dismutase (SOD1) in
      rodents has provided useful models for studying the pathogenesis of amyotrophic
      lateral sclerosis (ALS). Microglia have been shown to contribute to ALS disease
      progression in these models, although the mechanism of this contribution remains
      to be elucidated. Here, we present the first evidence of the effects of
      overexpression of mutant (TG G93A) and wild type (TG WT) human SOD1 transgenes on
      a set of functional properties of microglia relevant to ALS progression,
      including expression of integrin beta-1, spreading and migration, phagocytosis of
      apoptotic neuronal cell debris, and intracellular calcium changes in response to
      an inflammatory stimulus. RESULTS: TG SOD1 G93A but not TG SOD1 WT microglia had
      lower expression levels of the cell adhesion molecule subunit integrin beta-1
      than their NTG control cells [NTG (G93A) and NTG (WT), respectively, 92.8 +/-
      2.8% on TG G93A, 92.0 +/- 6.6% on TG WT, 100.0 +/- 1.6% on NTG (G93A), and 100.0
      +/- 2.7% on NTG (WT) cells], resulting in decreased spreading ability, with no
      effect on ability to migrate. Both TG G93A and TG WT microglia had reduced
      capacity to phagocytose apoptotic neuronal cell debris (13.0 +/- 1.3% for TG
      G93A, 16.5 +/- 1.9% for TG WT, 28.6 +/- 1.8% for NTG (G93A), and 26.9 +/- 2.8%
      for NTG (WT) cells). Extracellular stimulation of microglia with ATP resulted in
      smaller increase in intracellular free calcium in TG G93A and TG WT microglia
      relative to NTG controls (0.28 +/- 0.02 MUM for TG G93A, 0.24 +/- 0.03 MUM for TG
      WT, 0.39 +/- 0.03 MUM for NTG (G93A), and 0.37 +/- 0.05 MUM for NTG (WT)
      microglia). CONCLUSIONS: These findings indicate that, under resting conditions,
      microglia from mutant SOD1 transgenic mice have a reduced capacity to elicit
      physiological responses following tissue disturbances and that higher levels of
      stimulatory signals, and/or prolonged stimulation may be necessary to initiate
      these responses. Overall, resting mutant SOD1-overexpressing microglia may have
      reduced capacity to function as sensors of disturbed tissue/cellular homeostasis
      in the CNS and thus have reduced neuroprotective function.

PMID- 21943128
TI  - Assessment of data quality in an international multi-centre randomised trial of
      coronary artery surgery.
AB  - BACKGROUND: ART is a multi-centre randomised trial of cardiac surgery which
      provided a unique opportunity to evaluate the data from a large number of centres
      from a variety of countries. We attempted to assess data quality, including
      recruitment rates, timeliness and completeness of the data obtained from the
      centres in different socio-economic strata. METHODS: The analysis was based on
      the 2-page CRF completed at the 6 week follow-up. CRF pages were categorised into
      "clean" (no edit query) and "dirty" (any incomplete, inconsistent or illegible
      data). The timelines were assessed on the basis of the time interval from the
      visit and receipt of complete CRF. Data quality was defined as the number of data
      queries (in percent) and time delay (in days) between visit and receipt of
      correct data. Analyses were stratified according to the World Bank definitions
      into: "Developing" countries (Poland, Brazil and India) and "Developed" (Italy,
      UK, Austria and Australia). RESULTS: There were 18 centres in the "Developed" and
      10 centres in the "Developing" countries. The rate of enrolment did not differ
      significantly by economic level ("Developing":4.1 persons/month, "Developed":3.7
      persons/month). The time interval for the receipt of data was longer for
      "Developing" countries (median:37 days) compared to "Developed" ones (median:11
      days) (p < 0.001). The median number of data queries was 23% in "Developed"
      countries compared to 19% in "Developing" ones (p = ns). CONCLUSIONS: In this
      study we showed that data quality was comparable between centres from "Developed"
      and "Developing" countries. Data was received in a less timely fashion from
      Developing countries and appropriate systems should be instigated to minimize any
      delays. Close attention should be paid to the training of centres and to the
      central management of data quality. TRIAL REGISTRATION: ISRCTN46552265.

PMID- 21943129
TI  - Proteomic detection of a large amount of SCGFalpha in the stroma of GISTs after
      imatinib therapy.
AB  - BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most frequent
      mesenchymal tumors to develop in the digestive tract. These tumors are highly
      resistant to conventional chemotherapy and only the introduction of imatinib
      mesylate has improved the prognosis of patients. However, Response Evaluation
      Criteria in Solid Tumors are inappropriate for assessing tumor response, and the
      histological/pathological response to imatinib is variable, heterogeneous, and
      does not associate with clinical response. The effects of imatinib on responding
      GISTs are still being explored, and few studies correlate the clinical response
      with the histological response after pharmacological treatment. Recently,
      apoptosis and autophagy were suggested as possible alternative mechanisms of
      pharmacological response. METHODS: Here, we used a proteomic approach, combined
      with other analyses, to identify some molecular stromal components related to the
      response/behavior of resected, high-risk GISTs after neoadiuvant imatinib
      therapy. RESULTS: Our proteomic results indicate an elevated concentration of
      Stem Cell Growth Factor (SCGF), a hematopoietic growth factor having a role in
      the development of erythroid and myeloid progenitors, in imatinib-responsive
      tumor areas. SCGFalpha expression was detected by mass spectrometry,
      immunohistochemistry and/or western blot and attributed to acellular matrix of
      areas scored negative for KIT (CD117). RT-PCR results indicated that GIST samples
      did not express SCGF transcripts. The recently reported demonstration by
      Gundacker et al. 1 of the secretion of SCGF in mature pro-inflammatory dendritic
      cells would indicate a potential importance of SCGF in tissue inflammatory
      response. Accordingly, inflammatory infiltrates were detected in imatinib
      affected areas and the CD68-positivity of the SCGF-positive and KIT-negative
      areas suggested previous infiltration of monocytes/macrophages into these
      regions. Thus, chronic inflammation subsequent to imatinib treatment may
      determine monocyte/macrophage recruitment in imatinib-damaged areas; these areas
      also feature prominent tumor-cell loss that is replaced by dense hyalinization
      and fibrosis. CONCLUSIONS: Our studies highlight a possible role of SCGFalpha in
      imatinib-induced changes of GIST structure, consistent with a therapeutic
      response.

PMID- 21943130
TI  - The UlaG protein family defines novel structural and functional motifs grafted on
      an ancient RNase fold.
AB  - BACKGROUND: Bacterial populations are highly successful at colonizing new
      habitats and adapting to changing environmental conditions, partly due to their
      capacity to evolve novel virulence and metabolic pathways in response to stress
      conditions and to shuffle them by horizontal gene transfer (HGT). A common theme
      in the evolution of new functions consists of gene duplication followed by
      functional divergence. UlaG, a unique manganese-dependent metallo-beta-lactamase
      (MBL) enzyme involved in L-ascorbate metabolism by commensal and symbiotic
      enterobacteria, provides a model for the study of the emergence of new catalytic
      activities from the modification of an ancient fold. Furthermore, UlaG is the
      founding member of the so-called UlaG-like (UlaGL) protein family, a recently
      established and poorly characterized family comprising divalent (and perhaps
      trivalent) metal-binding MBLs that catalyze transformations on phosphorylated
      sugars and nucleotides. RESULTS: Here we combined protein structure-guided and
      sequence-only molecular phylogenetic analyses to dissect the molecular evolution
      of UlaG and to study its phylogenomic distribution, its relatedness with present
      day UlaGL protein sequences and functional conservation. Phylogenetic analyses
      indicate that UlaGL sequences are present in Bacteria and Archaea, with bona fide
      orthologs found mainly in mammalian and plant-associated Gram-negative and Gram
      positive bacteria. The incongruence between the UlaGL tree and known species
      trees indicates exchange by HGT and suggests that the UlaGL-encoding genes
      provided a growth advantage under changing conditions. Our search for more
      distantly related protein sequences aided by structural homology has uncovered
      that UlaGL sequences have a common evolutionary origin with present-day RNA
      processing and metabolizing MBL enzymes widespread in Bacteria, Archaea, and
      Eukarya. This observation suggests an ancient origin for the UlaGL family within
      the broader trunk of the MBL superfamily by duplication, neofunctionalization and
      fixation. CONCLUSIONS: Our results suggest that the forerunner of UlaG was
      present as an RNA metabolizing enzyme in the last common ancestor, and that the
      modern descendants of that ancestral gene have a wide phylogenetic distribution
      and functional roles. We propose that the UlaGL family evolved new metabolic
      roles among bacterial and possibly archeal phyla in the setting of a close
      association with metazoans, such as in the mammalian gastrointestinal tract or in
      animal and plant pathogens, as well as in environmental settings. Accordingly,
      the major evolutionary forces shaping the UlaGL family include vertical
      inheritance and lineage-specific duplication and acquisition of novel metabolic
      functions, followed by HGT and numerous lineage-specific gene loss events.

PMID- 21943131
TI  - Transforming growth factor-beta-stimulated clone-22 is a negative-feedback
      regulator of Ras / Raf signaling: Implications for tumorigenesis.
AB  - Transforming growth factor-beta (TGF-beta)-stimulated clone-22 (TSC-22), also
      called TSC22D1-2, is a putative tumor suppressor. We previously identified TSC-22
      downstream of an active mutant of fms-like tyrosine kinase-3 (Flt3). Here, we
      show that TSC-22 works as a tumor suppressor through inhibiting Ras/Raf
      signaling. Notably, TSC-22 was upregulated by Ras/Raf activation, whereas its
      upregulation was inhibited by concurrent STAT5 activation. Although TSC-22 was
      normally retained in the cytoplasm by its nuclear export signal (NES), Ras/Raf
      activation caused nuclear translocation of TSC-22, but not TSC22D1-1. Unlike
      glucocorticoid-induced leucine zipper (GILZ/TSC22D3-2) previously characterized
      as a negative regulator of Ras/Raf signaling, TSC-22 failed to interact
      physically with Ras/Raf. Importantly, transduction with TSC-22, but not TSC22D1
      1, suppressed the growth, transformation and tumorigenesis of NIH3T3 cells
      expressing oncogenic H-Ras: this suppression was enhanced by transduction with a
      TSC-22 mutant lacking NES that had accumulated in the nucleus. Collectively,
      upregulation and nuclear translocation of TSC-22 played an important role in the
      feedback suppression of Ras/Raf signaling. Consistently, TSC22D1-deficient mice
      were susceptible to tumorigenesis in a mouse model of chemically-induced liver
      tumors bearing active mutations of Ras/Raf. Thus, TSC-22 negatively regulated
      Ras/Raf signaling through a mechanism different from GILZ, implicating TSC-22 as
      a novel suppressor of oncogenic Ras/Raf-induced tumors.

PMID- 21943133
TI  - The new American Thyroid Association Guidelines for thyroid disease during
      pregnancy and postpartum: a blueprint for improving prenatal care.

PMID- 21943134
TI  - Personal considerations on the 2011 American Thyroid Association and the 2007
      Endocrine Society pregnancy and thyroid disease guidelines.

PMID- 21943132
TI  - The effect of a periodontal intervention on cardiovascular risk markers in
      Indigenous Australians with periodontal disease: the PerioCardio study.
AB  - BACKGROUND: Indigenous Australians experience an overwhelming burden of chronic
      disease, including cardiovascular diseases. Periodontal disease (inflammation of
      the tissues surrounding teeth) is also widespread, and may contribute to the risk
      of cardiovascular diseases via pathogenic inflammatory pathways. This study will
      assess measures of vascular health and inflammation in Indigenous Australian
      adults with periodontal disease, and determine if intensive periodontal therapy
      improves these measures over a 12 month follow-up. The aims of the study are: (i)
      to determine whether there is a dose response relationship between extent and
      severity of periodontal disease and measures of vascular health and inflammation
      among Indigenous Australian adults with moderate to severe periodontal disease;
      and (ii) to determine the effects of periodontal treatment on changes in measures
      of vascular health and inflammation in a cohort of Indigenous Australians.
      METHODS/DESIGN: This study will be a randomised, controlled trial, with
      predominantly blinded assessment of outcome measures and blinded statistical
      analysis. All participants will receive the periodontal intervention benefits
      (with the intervention delayed 12 months in participants who are randomised to
      the control arm). Participants will be Indigenous adults aged >=25 years from
      urban centres within the Top End of the Northern Territory, Australia.
      Participants assessed to have moderate or severe periodontal disease will be
      randomised to the study's intervention or control arm. The intervention involves
      intensive removal of subgingival and supragingival calculus and plaque biofilm by
      scaling and root-planing. Study visits at baseline, 3 and 12 months, will
      incorporate questionnaires, non-fasting blood and urine samples, body
      measurements, blood pressure, periodontal assessment and non-invasive measures of
      vascular health (pulse wave velocity and carotid intima-media thickness). Primary
      outcome measures are pulse wave velocity and carotid intima-media thickness.
      DISCUSSION: The study will assess the periodontal-cardiovascular disease
      relationship among Indigenous Australian adults with periodontal disease, and the
      effectiveness of an intervention aimed at improving periodontal and
      cardiovascular health. Efforts to understand and improve Indigenous oral health
      and cardiovascular risk may serve as an important means of reducing the gap
      between Indigenous and non-Indigenous health in Australia. TRIAL REGISTRATION:
      Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12610000817044.

PMID- 21943135
TI  - Pregnancy and thyroid diseases in China.

PMID- 21943136
TI  - Subclinical hypothyroidism in pregnancy: intellectual development of offspring.
AB  - BACKGROUND: The effects of maternal subclinical hypothyroidism (M-SCH) on the
      neuropsychological development of the offspring are not clear. We evaluated the
      intellectual development of children of mothers who had M-SCH during the
      pregnancy for these children. METHODS: Sixty-two children were recruited. After
      excluding those age < 4 or age > 15, 44 were enrolled. The mothers of these
      children were part of a sub-pool of 90, of 441 hypothyroid women of reproductive
      age seen in Tehran endocrine clinics between 1991 and 2003 and who were observed
      during gestation. Mothers were receiving levothyroxine (LT4) before gestation.
      Mothers of 19 children (control group) had normal serum thyrotropin (TSH) during
      the pregnancy that produced these children. Mothers of the other 25 children had
      increased TSH during the comparable pregnancy. Nineteen mothers had M-SCH (case
      group) and six had overt hypothyroidism. Serum TSH and free T4 (FT4) and urine
      iodine were measured, and seven cognitive performance and intelligence quotient
      (IQ) tests were performed. RESULTS: Case children were similar to control
      children with respect to gender, age, parental education, maternal age at time of
      pregnancy and at the time of their hypothyroidism, percent mothers having thyroid
      peroxidase antibodies, LT4 dose of mothers during pregnancy, gestational age at
      delivery, birth weight, and duration of breast feeding. Maternal TSH (mean +/-
      standard deviation) in the case group during their mother's pregnancies was 11.3
      +/- 5.3 and 1.4 +/- 1.0 mU/L in the controls (p < 0.001). Serum TSH, FT4 and
      urinary iodine concentrations were similar in the two groups. Total IQ,
      performance IQ, and verbal IQ were similar, being 120 +/- 14, 117 +/- 12, and 121
      +/- 16, respectively, in the case group and 121 +/- 11, 120 +/- 7, and 117 +/- 15
      in the control group. Cognitive performance tests were similar in both groups. No
      relationships were observed between variables and IQ except for education level
      of the mother and neonatal weight. CONCLUSION: IQ level and cognitive performance
      of children born to LT4-treated hypothyroid mothers is similar in those whose
      mothers have M-SCH during pregnancy compared with those whose mothers have normal
      serum TSH concentrations during pregnancy.

PMID- 21943137
TI  - Choice of antithythroid drugs in pregnancy.

PMID- 21943139
TI  - Release instructions for hyperthyroid patients treated with I-131.

PMID- 21943144
TI  - The extramural metastasis might be categorized in lymph node staging for
      colorectal cancer.
AB  - ABSTRACT:  BACKGROUND: The objective of this study is to assess the clinical
      significance and prognostic impact of extramural metastasis in colorectal
      carcinoma and establish an optimal categorization in the staging system. METHODS:
      To determine the frequency and prognostic significance of extramural metastasis,
      from 2000 to 2005, a total of 1,215 patients with colorectal cancer who underwent
      surgical resection were recruited into this study. Individual demographic and
      clinicopathologic data were collected including tumor stage, nodal stage, tumor
      histology, degree of tumor differentiation, and presence of lymphovascular
      invasion. After surgery, all patients received standard treatments and follow-up,
      which were closed in April 2010. RESULTS: EM was detected in 167 (13.7%) patients
      and in 230 (1.8%) of the 12,534 nodules retrieved as 'lymph nodes'. The incidence
      of extramural metastasis was significantly higher in patients with large tumors,
      deeper invasive depth and more lymph node metastasis (P < 0.001). After curative
      operation, overall survival was significantly worse for patients with extramural
      metastasis than those without (P < 0.001). Multivariate analysis identified
      extramural metastasis as an independent prognostic factor (RR = 2.1, 95%CI:1.5
      3.0). By using the Akaike information criterion (AIC), N staging was capable of
      predicting survival outcome with the highest accuracy when both nodal involvement
      and extramural metastasis were treated together as N factors(AIC = 1025.3).
      CONCLUSION: Extramural metastasis might be diagnosed as replaced lymph nodes in
      the process of classification, thus forming a new categorization.

PMID- 21943145
TI  - CCMG statement on direct-to-consumer genetic testing.

PMID- 21943146
TI  - Preoperative radiological characterization of hepatic angiomyolipoma using
      magnetic resonance imaging and contrast-enhanced ultrasonography: a case report.
AB  - INTRODUCTION: A hepatic angiomyolipoma is a rare benign tumor of the liver
      composed of a mixture of smooth muscle cells, blood vessels and a variable amount
      of adipose tissue. Differentiating them from malignant liver tumors can often be
      very difficult. CASE PRESENTATION: We report the case of a 43-year-old Caucasian
      man presenting with a large liver mass in the right lobe. The results of magnetic
      resonance imaging and contrast-enhanced ultrasonography were consistent with a
      well-demarcated adipose tissue- containing tumor, showing prolonged
      hyperperfusion in comparison with the surrounding liver tissue. Surgery was
      performed and the diagnosis of hepatic angiomyolipoma was made with
      histopathology. CONCLUSION: Preoperative radiological characterization using
      magnetic resonance imaging and contrast-enhanced ultrasonography may improve
      diagnostic accuracy of hepatic angiomyolipoma. Identification of smooth muscle
      cells, blood vessels and adipose tissue with a positive immunohistochemical
      reaction for HMB-45 is the final evidence for an angiomyolipoma.

PMID- 21943147
TI  - Oesophageal perforation: a diagnostic and therapeutic challenge in a resource
      limited setting. A report of three cases.
AB  - BACKGROUND: Oesophageal perforation is a condition associated with a high
      mortality. Its management is still controversial with operative treatment being
      favoured but a shift to conservative management is occurring. Very little exists
      in medical literature about its management in Sub-Saharan Africa, where the
      paucity of thoracic surgeons is compounded by limited diagnostic and therapeutic
      facilities. CASE PRESENTATION: We report three cases of oesophageal perforation
      which were all treated conservatively with tube thoracostomy, nil by mouth with
      feeding gastrostomy, intravenous antibiotics and chest physiotherapy. Two
      patients achieved oesophageal healing but one died due to severe septicaemia.
      CONCLUSION: In a resource restricted setting, conservative management which
      includes enteral nutrition by feeding gastrostomy, tube thoracostomy to drain
      inter pleural contaminants, intravenous antibiotics and chest physiotherapy is a
      safe and effective treatment for oesophageal perforations.

PMID- 21943148
TI  - Increase of cells expressing PD-L1 in bovine leukemia virus infection and
      enhancement of anti-viral immune responses in vitro via PD-L1 blockade.
AB  - The inhibitory receptor programmed death-1 (PD-1) and its ligand, programmed
      death-ligand 1 (PD-L1) are involved in immune evasion mechanisms for several
      pathogens causing chronic infections. Blockade of the PD-1/PD-L1 pathway restores
      anti-virus immune responses, with concomitant reduction in viral load. In a
      previous report, we showed that, in bovine leukemia virus (BLV) infection, the
      expression of bovine PD-1 is closely associated with disease progression.
      However, the functions of bovine PD-L1 are still unknown. To investigate the role
      of PD-L1 in BLV infection, we identified the bovine PD-L1 gene, and examined PD
      L1 expression in BLV-infected cattle in comparison with uninfected cattle. The
      deduced amino acid sequence of bovine PD-L1 shows high homology to the human and
      mouse PD-L1. The proportion of PD-L1 positive cells, especially among B cells,
      was upregulated in cattle with the late stage of the disease compared to cattle
      at the aleukemic infection stage or uninfected cattle. The proportion of PD-L1
      positive cells correlated positively with prediction markers for the progression
      of the disease such as leukocyte number, virus load and virus titer whilst on the
      contrary, it inversely correlated with the degree of interferon-gamma expression.
      Blockade of the PD-1/PD-L1 pathway in vitro by PD-L1-specific antibody
      upregulated the production of interleukin-2 and interferon-gamma, and
      correspondingly, downregulated the BLV provirus load and the proportion of BLV
      gp51 expressing cells. These data suggest that PD-L1 induces immunoinhibition in
      disease progressed cattle during chronic BLV infection. Therefore, PD-L1 would be
      a potential target for developing immunotherapies against BLV infection.

PMID- 21943150
TI  - Effects of a denture adhesive in edentulous patients after maxillectomy.
AB  - OBJECTIVE: The objective of this study is to evaluate the usefulness of a denture
      adhesive in edentulous patients after maxillectomy. BACKGROUND: Maxillectomy
      patients suffer from functional impairments. Denture adhesives (DAs) are the
      solution in such patients. However, little is known about DAs in maxillectomy
      patients. MATERIALS AND METHODS: Eight edentulous patients who had undergone
      maxillectomy were included and divided into three groups. Group 1 (half <=
      remaining residual maxilla), Group 2 (quarter < remaining residual maxilla <
      half) and Group 3 (remaining residual maxilla <= quarter). They were evaluated by
      a speech intelligibility test and a mixing ability test, respectively. A cream
      type DA called New Poligrip((r)) (GlaxoSmithKline, Tokyo, Japan) was used.
      RESULTS: Applying the DA, speech intelligibility showed a higher score than the
      data without DA. CONCLUSION: The effects of using a DA depend on the amount of
      the remaining residual maxilla. Our study showed that if the remaining residual
      maxilla is less than a quarter (Group 3), it is difficult to have confidence in
      the effectiveness of the DA to improve masticatory function. On the other hand,
      the use a DA showed improved speech intelligibility test values in all groups.

PMID- 21943149
TI  - MicroRNAs in rhabdomyosarcoma: pathogenetic implications and translational
      potentiality.
AB  - There is growing evidence that interconnections among molecular pathways
      governing tissue differentiation are nodal points for malignant transformation.
      In this scenario, microRNAs appear as crucial players. This class of non-coding
      small regulatory RNA molecules controls developmental programs by modulating gene
      expression through post-transcriptional silencing of target mRNAs. During
      myogenesis, muscle-specific and ubiquitously-expressed microRNAs tightly control
      muscle tissue differentiation. In recent years, microRNAs have emerged as
      prominent players in cancer as well. Rhabdomyosarcoma is a pediatric skeletal
      muscle-derived soft-tissue sarcoma that originates from myogenic precursors
      arrested at different stages of differentiation and that continue to proliferate
      indefinitely. MicroRNAs involved in muscle cell fate determination appear down
      regulated in rhabdomyosarcoma primary tumors and cell lines compared to their
      normal counterparts. More importantly, they behave as tumor suppressors in this
      malignancy, as their re-expression is sufficient to restore the differentiation
      capability of tumor cells and to prevent tumor growth in vivo. In addition, up
      regulation of pro-oncogenic microRNAs has also been recently detected in
      rhabdomyosarcoma.In this review, we provide an overview of current knowledge on
      microRNAs de-regulation in rhabdomyosarcoma. Additionally, we examine the
      potential of microRNAs as prognostic and diagnostic markers in this soft-tissue
      sarcoma, and discuss possible therapeutic applications and challenges of a
      "microRNA therapy".

PMID- 21943151
TI  - Leptin and leptin receptor polymorphisms are associated with poor outcome (death)
      in patients with non-appendicular secondary peritonitis.
AB  - INTRODUCTION: Leptin (LEP) and its receptor (LEPR) participate in the
      immunological response during infection. LEP serum levels rise during sepsis. In
      patients with peritonitis, an insufficient elevation in serum LEP is associated
      with an increased risk of death. As gene variants of LEP and LEPR have been
      associated with diverse pathologic conditions, we explored the association of
      genetic polymorphisms of LEP or LEPR with death in patients with secondary
      peritonitis. METHODS: A case control study was undertaken. LEP Gene -2548G > A
      and the LEPR Gene 223A > G polymorphism were determined in 74 patients. The odds
      ratio of genotype and allele distribution in survival (control) versus death
      (case) among patients was calculated. Serum LEP, interleukin (IL)-6, tumour
      necrosis factor alpha, C-reactive protein (C-RP), IL-10 and IL-13 levels were
      analyzed in 34 patients. RESULTS: There were significant differences in genotype
      and allele distribution between survivors and non-survivors for -2548G > A and
      223A > G polymorphisms. The presence of the mutant allele A, in -2548, had an
      odds ratio of 4.64 (95% CI 1.22, 17.67) with significance (P = 0.017) in the risk
      of death. The presence of mutant allele G, in 223, had an odds ratio of 3.57 (95%
      CI 1.06, 12.01) with significance in the risk of death (P = 0.033). The presence
      of allele A in the -2548 polymorphism was associated with differences in serum
      LEP (P = 0.013), and IL-10 (P = 0.0001). The presence of allele G in 223
      polymorphism was likewise correlated with differences in serum LEP (P < 0001), C
      RP (P = 0.033), and IL-10 (P = 0.043). CONCLUSIONS: The polymorphisms studied are
      associated with death in patients with peritonitis of non-appendicular origin.
      This association is stronger than many known risk-factors related to peritonitis
      severity, and is independent of body mass. The physiopathologic mechanism is
      possibly related to an insufficient increase in the elevation of serum LEP
      levels, and is unrelated to body mass.

PMID- 21943152
TI  - The dual origin of the peripheral olfactory system: placode and neural crest.
AB  - BACKGROUND: The olfactory epithelium (OE) has a unique capacity for continuous
      neurogenesis, extending axons to the olfactory bulb with the assistance of
      olfactory ensheathing cells (OECs). The OE and OECs have been believed to develop
      solely from the olfactory placode, while the neural crest (NC) cells have been
      believed to contribute only the underlying structural elements of the olfactory
      system. In order to further elucidate the role of NC cells in olfactory
      development, we examined the olfactory system in the transgenic mice Wnt1
      Cre/Floxed-EGFP and P0-Cre/Floxed-EGFP, in which migrating NC cells and its
      descendents permanently express GFP, and conducted transposon-mediated cell
      lineage tracing studies in chick embryos. RESULTS: Examination of these
      transgenic mice revealed GFP-positive cells in the OE, demonstrating that NC
      derived cells give rise to OE cells with morphologic and antigenic properties
      identical to placode-derived cells. OECs were also positive for GFP, confirming
      their NC origin. Cell lineage tracing studies performed in chick embryos
      confirmed the migration of NC cells into the OE. Furthermore, spheres cultured
      from the dissociated cells of the olfactory mucosa demonstrated self-renewal and
      trilineage differentiation capacities (neurons, glial cells, and myofibroblasts),
      demonstrating the presence of NC progenitors in the olfactory mucosa. CONCLUSION:
      Our data demonstrates that the NC plays a larger role in the development of the
      olfactory system than previously believed, and suggests that NC-derived cells may
      in part be responsible for the remarkable capacity of the OE for neurogenesis and
      regeneration.

PMID- 21943153
TI  - Type 2 diabetes and pre-diabetes are associated with obstructive sleep apnea in
      extremely obese subjects: a cross-sectional study.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is a common yet underdiagnosed
      condition. The aim of our study is to test whether prediabetes and type 2
      diabetes are associated with obstructive sleep apnea (OSA) in extremely obese
      (BMI >= 40 kg/m2) subjects. METHODS: One hundred and thirty seven consecutive
      extremely obese patients (99 females) from a controlled clinical trial [MOBIL
      study (Morbid Obesity treatment, Bariatric surgery versus Intensive Lifestyle
      intervention Study) (ClinicalTrials.gov number NCT00273104)] underwent
      somnography with Embletta(r) and a 2-hour oral glucose tolerance test (OGTT). OSA
      was defined by an apnea-hypopnea index (AHI) >= 5 events/hour. Patients were
      categorized into three groups according to criteria from the American Diabetes
      Association: normal glucose tolerance, pre-diabetes and type 2 diabetes. Multiple
      logistic regression analysis was used to identify possible determinants of OSA.
      RESULTS: The patients had a mean (SD) age of 43 (11) years and a body mass index
      (BMI) of 46.9 (5.7) kg/m2. Males had significantly higher AHI than females, 29
      (25) vs 12 (17) events/hour, p < 0.001. OSA was observed in 81% of men and in 55%
      of women, p = 0.008. Twenty-nine percent of subjects had normal glucose
      tolerance, 42% had pre-diabetes and 29% had type 2 diabetes. Among the patients
      with normal glucose tolerance 33% had OSA, while 67% of the pre-diabetic patients
      and 78% of the type 2 diabetic patients had OSA, p < 0.001. After adjusting for
      age, gender, BMI, high sensitive CRP and HOMA-IR, both pre-diabetes and type 2
      diabetes were still associated with OSA, odds ratios 3.18 (95% CI 1.00, 10.07), p
      = 0.049 and 4.17 (1.09, 15.88), p = 0.036, respectively. Mean serum leptin was
      significantly lower in the OSA than in the non-OSA group, while other measures of
      inflammation did not differ significantly between groups. CONCLUSIONS: Type 2
      diabetes and pre-diabetes are associated with OSA in extremely obese subjects.
      TRIAL REGISTRATION: MOBIL-study (Morbid Obesity treatment, Bariatric surgery
      versus Intensive Lifestyle intervention Study) (ClinicalTrials.gov number
      NCT00273104).

PMID- 21943154
TI  - Accuracy of peak VO2 assessments in career firefighters.
AB  - BACKGROUND: Sudden cardiac death is the leading cause of on-duty death in United
      States firefighters. Accurately assessing cardiopulmonary capacity is critical to
      preventing, or reducing, cardiovascular events in this population. METHODS: A
      total of 83 male firefighters performed Wellness-Fitness Initiative (WFI) maximal
      exercise treadmill tests and direct peak VO2 assessments to volitional fatigue.
      Of the 83, 63 completed WFI sub-maximal exercise treadmill tests for comparison
      to directly measured peak VO2 and historical estimations. RESULTS: Maximal heart
      rates were overestimated by the traditional 220-age equation by about 5 beats per
      minute (p < .001). Peak VO2 was overestimated by the WFI maximal exercise
      treadmill and the historical WFI sub-maximal estimation by ~ 1MET and ~ 2 METs,
      respectively (p < 0.001). The revised 2008 WFI sub-maximal treadmill estimation
      was found to accurately estimate peak VO2 when compared to directly measured peak
      VO2. CONCLUSION: Accurate assessment of cardiopulmonary capacity is critical in
      determining appropriate duty assignments, and identification of potential
      cardiovascular problems, for firefighters. Estimation of cardiopulmonary fitness
      improves using the revised 2008 WFI sub-maximal equation.

PMID- 21943155
TI  - In vitro assessment of tobacco smoke toxicity at the BBB: do antioxidant
      supplements have a protective role?
AB  - BACKGROUND: Tobacco smoke (TS) contains highly reactive oxygen species (such as
      hydrogen peroxide, peroxynitrite, etc), which cause oxidative damage in vascular
      tissue and may exacerbate inflammatory events leading to the blood-brain barrier
      damage (BBBD) which accompanies the development of a variety of neurological
      disorders. Smokers often have elevated leukocyte counts (primarily neutrophils
      and monocytes), and significant decreases in plasma alpha-tocopherol (vitamin E)
      and ascorbic acid (vitamin C) levels due to increased anti-oxidative mobilization
      in response to oxidative stress evoked by TS. For this purpose, using static
      culture systems and a well-established dynamic in vitro BBB model (DIV-BBB) we
      tested the hypothesis that antioxidant vitamin supplementation (E and/or C) can
      protect the BBB during exposure to whole soluble TS. RESULTS: TS exacerbates
      inflammatory events and leads to endothelial overexpression of vascular adhesion
      molecules (VCAM-1, P-selectin and E-selectin), release of pro-inflammatory
      cytokines (TNF-alpha and IL-6) and nitric oxide (NO), release and activation of
      matrix metalloproteinases (MMP-2 and MMP-9), monocytic maturation into
      macrophages, and adhesion to the vascular endothelium. Furthermore, TS altered
      the normal glucose metabolic behaviour of in vitro BBB capillaries and caused a
      period of transient anaerobic respiration to meet the cellular bioenergetic
      demand. Pre-treatment with antioxidant vitamins (C and/or E) effectively reduced
      the pro-inflammatory activity associated with TS, protecting the viability and
      functions of the BBB. CONCLUSION: Our results have shown that loss of endothelial
      viability as well as BBB function and integrity caused by TS exposure can be
      prevented or at least reduced by normal physiologic concentrations of antioxidant
      vitamins in vitro.

PMID- 21943156
TI  - Effects of obesity and chronic low back pain on gait.
AB  - BACKGROUND: Obesity is often associated with low back pain (LBP). Despite
      empirical evidence that LBP induces gait abnormalities, there is a lack of
      quantitative analysis of the combined effect of obesity and LBP on gait. The aim
      of our study was to quantify the gait pattern of obese subjects with and without
      LBP and normal-mass controls by using Gait Analysis (GA), in order to investigate
      the cumulative effects of obesity and LBP on gait. METHODS: Eight obese females
      with chronic LBP (OLG; age: 40.5 +/- 10.1 years; BMI: 42.39 +/- 5.47 Kg/m(2)), 10
      obese females (OG; age: 33.6 +/- 5.2 years; BMI: 39.26 +/- 2.39 Kg/m(2)) and 10
      healthy female subjects (CG; age: 33.4 +/- 9.6 years; BMI: 22.8 +/- 3.2 Kg/m(2)),
      were enrolled in this study and assessed with video recording and GA. RESULTS AND
      DISCUSSION: OLG showed longer stance duration and shorter step length when
      compared to OG and CG. They also had a low pelvis and hip ROM on the frontal
      plane, a low knee flexion in the swing phase and knee range of motion, a low
      dorsiflexion in stance and swing as compared to OG. No statistically significant
      differences were found in ankle power generation at push-off between OLG and OG,
      which appeared lower if compared to CG. At hip level, both OLG and OG exhibited
      high power generation levels during stance, with OLG showing the highest values.
      CONCLUSIONS: Our results demonstrated that the association of obesity and LBP
      affects more the gait pattern than obesity alone. OLG were in fact characterised
      by an altered knee and ankle strategy during gait as compared to OG and CG. These
      elements may help optimizing rehabilitation planning and treatment in these
      patients.

PMID- 21943157
TI  - Inhibitory effects of inhaled complex traditional Chinese medicine on early and
      late asthmatic responses induced by ovalbumin in sensitized guinea pigs.
AB  - BACKGROUND: Many formulae of traditional Chinese medicines (TCMs) have been used
      for antiasthma treatment dating back many centuries. There is evidence to suggest
      that TCMs are effective as a cure for this allergenic disease administered via
      gastric tubes in animal studies; however, their efficacy, safety and side effects
      as an asthmatic therapy are still unclear. METHODS: In this study, guinea pigs
      sensitized with ovalbumin (OVA) were used as an animal model for asthma
      challenge, and the sensitization of animals by bronchial reactivity to
      methacholine (Mch) and the IgE concentration in the serum after OVA challenge
      were estimated. Complex traditional Chinese herbs (CTCM) were administered to the
      animals by nebulization, and the leukocytes were evaluated from bronchoalveolar
      lavage fluid (BALF). RESULTS: The results showed that inhalation of CTCM could
      abolish the increased lung resistance (13-fold increase) induced by challenge
      with OVA in the early asthmatic response (EAR), reducing to as low as baseline (1
      fold). Moreover, our results indicated higher IgE levels (range, 78-83 ng/ml) in
      the serum of sensitized guinea pigs than in the unsensitized controls (0.9 +/-
      0.256 ng/ml). In addition, increased total leukocytes and higher levels of
      eosinophils and neutrophils were seen 6 hours after challenge, and the increased
      inflammatory cells were reduced by treatment with CTCM inhalation. The
      interleukin-5 (IL-5) level in BALF was also reduced by CTCM. CONCLUSION: Our
      findings indicate a novel method of administering traditional Chinese medicines
      for asthma treatment in an animal model that may be more effective than
      traditional methods.

PMID- 21943159
TI  - MicroRNA-134 as a potential plasma biomarker for the diagnosis of acute pulmonary
      embolism.
AB  - BACKGROUND: Acute pulmonary embolism (APE) remains a diagnostic challenge due to
      a variable clinical presentation and the lack of a reliable screening tool.
      MicroRNAs (miRNAs) regulate gene expression in a wide range of pathophysiologic
      processes. Circulating miRNAs are emerging biomarkers in heart failure, type 2
      diabetes and other disease states; however, using plasma miRNAs as biomarkers for
      the diagnosis of APE is still unknown. METHODS: Thirty-two APE patients, 32
      healthy controls, and 22 non-APE patients (reported dyspnea, chest pain, or
      cough) were enrolled in this study. The TaqMan miRNA microarray was used to
      identify dysregulated miRNAs in the plasma of APE patients. The TaqMan-based
      miRNA quantitative real-time reverse transcription polymerase chain reactions
      were used to validate the dysregulated miRNAs. The receiver-operator
      characteristic (ROC) curve analysis was conducted to evaluate the diagnostic
      accuracy of the miRNA identified as the candidate biomarker. RESULTS: Plasma
      miRNA-134 (miR-134) level was significantly higher in the APE patients than in
      the healthy controls or non-APE patients. The ROC curve showed that plasma miR
      134 was a specific diagnostic predictor of APE with an area under the curve of
      0.833 (95% confidence interval, 0.737 to 0.929; P < 0.001). CONCLUSIONS: Our
      findings indicated that plasma miR-134 could be an important biomarker for the
      diagnosis of APE. Because of this finding, large-scale investigations are
      urgently needed to pave the way from basic research to clinical utilization.

PMID- 21943160
TI  - The tele-intensive care unit during a disaster: seamless transition from routine
      operations to disaster mode.
AB  - Disaster plans, during the actual disaster, often do not function as conceived
      and designed. Disaster or emergency situations may not present as anticipated in
      planning sessions confounding the intent of disaster planners. Systems that are
      created and shelved awaiting the disaster may be dysfunctional when needed due to
      problems such as failed batteries, forgotten training, misplaced equipment, the
      retraining curve, or software that has not been updated. We report here the
      smooth and seamless transition to disaster mode from a system in daily use and
      therefore operational when needed.

PMID- 21943158
TI  - Genetic variants in LPL, OASL and TOMM40/APOE-C1-C2-C4 genes are associated with
      multiple cardiovascular-related traits.
AB  - BACKGROUND: Genome-wide association studies (GWAS) have become a major strategy
      for genetic dissection of human complex diseases. Analysing multiple phenotypes
      jointly may improve both our ability to detect genetic variants with multiple
      effects and our understanding of their common features. Allelic associations for
      multiple biochemical traits (serum alanine aminotransferase, aspartate
      aminotransferase, butrylycholinesterase (BCHE), C-reactive protein (CRP),
      ferritin, gamma glutamyltransferase (GGT), glucose, high-density lipoprotein
      cholesterol (HDL), insulin, low-density lipoprotein cholesterol (LDL),
      triglycerides and uric acid), and body-mass index, were examined. METHODS: We
      aimed to identify common genetic variants affecting more than one of these traits
      using genome-wide association analysis in 2548 adolescents and 9145 adults from
      4986 Australian twin families. Multivariate and univariate associations were
      performed. RESULTS: Multivariate analyses identified eight loci, and univariate
      association analyses confirmed two loci influencing more than one trait at p < 5
      * 10-8. These are located on chromosome 8 (LPL gene affecting HDL and
      triglycerides) and chromosome 19 (TOMM40/APOE-C1-C2-C4 gene cluster affecting LDL
      and CRP). A locus on chromosome 12 (OASL gene) showed effects on GGT, LDL and
      CRP. The loci on chromosomes 12 and 19 unexpectedly affected LDL cholesterol and
      CRP in opposite directions. CONCLUSIONS: We identified three possible loci that
      may affect multiple traits and validated 17 previously-reported loci. Our study
      demonstrated the usefulness of examining multiple phenotypes jointly and
      highlights an anomalous effect on CRP, which is increasingly recognised as a
      marker of cardiovascular risk as well as of inflammation.

PMID- 21943161
TI  - Health literacy and willingness to use online health information by teens with
      asthma and diabetes.
AB  - OBJECTIVE: This study measured health literacy in a population of teens in
      treatment for asthma or diabetes and tested the association between health
      literacy and willingness to use online health resources. MATERIALS AND METHODS:
      About 180 patients aged 13-18 years treated for asthma or diabetes in specialty
      care clinics completed assessments of demographic characteristics, health
      literacy, and Internet access and use. Teens were provided a resource page
      listing selected publically available health-related Web sites and asked about
      perceived ease of use, perceived usefulness, and intent to use the listed Web
      sites. The relationship between demographic characteristics, health literacy, and
      online health information use was tested using chi-squared or Fisher's exact
      test. Predictors of intent to use resource page Web sites were assessed using
      bivariate and multivariate ordinal logistic regression. RESULTS: About 92% of
      participants had adequate health literacy. Over 50% of participants had
      previously searched online for health information. Older age was the only
      significant predictor of health information search. Most teens (79%) reported
      intent to use at least one Web site from the resource page at least occasionally
      within the next 3 months. Higher health literacy (odds ratio [OR]=6.24, p<0.01)
      and stronger perceived usefulness (OR=1.74, p=0.01) were associated with greater
      intent for regular use, after controlling for demographic and Internet access
      variables. CONCLUSIONS: Teens with lower health literacy searched online for
      health information as often as peers with higher literacy, but were less likely
      to express the intent to use recommended sites. Belief in the usefulness of a Web
      site is the strongest attitudinal predictor of intended future use.

PMID- 21943163
TI  - Schmidtea mediterranea phylogeography: an old species surviving on a few
      Mediterranean islands?
AB  - BACKGROUND: Schmidtea mediterranea (Platyhelminthes, Tricladida, Continenticola)
      is found in scattered localities on a few islands and in coastal areas of the
      western Mediterranean. Although S. mediterranea is the object of many
      regeneration studies, little is known about its evolutionary history. Its present
      distribution has been proposed to stem from the fragmentation and migration of
      the Corsica-Sardinia microplate during the formation of the western Mediterranean
      basin, which implies an ancient origin for the species. To test this hypothesis,
      we obtained a large number of samples from across its distribution area. Using
      known and new molecular markers and, for the first time in planarians, a
      molecular clock, we analysed the genetic variability and demographic parameters
      within the species and between its sexual and asexual populations to estimate
      when they diverged. RESULTS: A total of 2 kb from three markers (COI, CYB and a
      nuclear intron N13) was amplified from ~200 specimens. Molecular data clustered
      the studied populations into three groups that correspond to the west, central
      and southeastern geographical locations of the current distribution of S.
      mediterranea. Mitochondrial genes show low haplotype and nucleotide diversity
      within populations but demonstrate higher values when all individuals are
      considered. The nuclear marker shows higher values of genetic diversity than the
      mitochondrial genes at the population level, but asexual populations present
      lower variability than the sexual ones. Neutrality tests are significant for some
      populations. Phylogenetic and dating analyses show the three groups to be
      monophyletic, with the west group being the basal group. The time when the
      diversification of the species occurred is between ~20 and ~4 mya, although the
      asexual nature of the western populations could have affected the dating
      analyses. CONCLUSIONS: S. mediterranea is an old species that is sparsely
      distributed in a harsh habitat, which is probably the consequence of the
      migration of the Corsica-Sardinia block. This species probably adapted to
      temperate climates in the middle of a changing Mediterranean climate that
      eventually became dry and hot. These data also suggest that in the mainland
      localities of Europe and Africa, sexual individuals of S. mediterranea are being
      replaced by asexual individuals that are either conspecific or are from other
      species that are better adapted to the Mediterranean climate.

PMID- 21943162
TI  - Telephonic monitoring and optimization of inhaler technique.
AB  - INTRODUCTION: Improper inhaler technique is a common problem affecting asthma
      control and healthcare costs. Telephonic asthma management can increase access to
      care while reducing costs and hospitalizations. However, no reliable method has
      been established for telephonically evaluating and correcting inhaler technique.
      OBJECTIVE: The purpose of this study was to pilot test a method for assessing and
      correcting patient inhaler technique via telephone. METHODS: Participants (n=30)
      were adults with asthma using metered-dose inhalers (MDIs) and diskus inhalers. A
      pharmacist was located in one room and communicated via telephone with a
      participant in another room. The pharmacist telephonically assessed and taught
      inhaler technique. Participants were video-recorded, and videos were later
      examined by a second pharmacist to visually evaluate inhaler technique.
      Participants were assigned pre- and posteducation inhaler technique scores for
      the telephonic and video assessments. Scores were based on summated scales for
      MDI (0-9) and diskus (0-11) inhalers. Paired samples t-tests were used to compare
      telephone and video assessments. RESULTS: Findings indicated a significant
      difference between the telephone and video assessments of MDI technique (p<0.05);
      however, no difference was found for the diskus inhaler. Comparing pre- and
      posteducation inhaler technique for MDI and diskus, mean scores significantly
      improved from 5.7 to 7.8 (p<0.05) and from 8.5 to 10.4 (p<0.05), respectively.
      CONCLUSIONS: The telephonic method was able to improve and detect some
      deficiencies in patients' inhaler technique. However, modifications and further
      investigation will more clearly determine the role and value of such a telephonic
      intervention.

PMID- 21943164
TI  - High acceptance of home-based HIV counseling and testing in an urban community
      setting in Uganda.
AB  - BACKGROUND: HIV testing is a key component of prevention and an entry point into
      HIV/AIDS treatment and care however, coverage and access to testing remains low
      in Uganda. Home-Based HIV Counseling and Testing (HBHCT) has potential to
      increase access and early identification of unknown HIV/AIDS disease. This study
      investigated the level of acceptance of Home-Based HIV Counseling and Testing
      (HBHCT), the HIV sero-prevalence and the factors associated with acceptance of
      HBHCT in an urban setting. METHODS: A cross-sectional house-to-house survey was
      conducted in Rubaga division of Kampala from January-June 2009. Residents aged >=
      15 years were interviewed and tested for HIV by trained nurse-counselors using
      the national standard guidelines. Acceptance of HBHCT was defined as consenting,
      taking the HIV test and receipt of results offered during the home visit.
      Multivariable logistic regression analysis was performed to determine significant
      factors associated with acceptance of HBHCT. RESULTS: We enrolled 588
      participants, 408 (69%, 95% CI: 66%-73%) accepted testing. After adjusting for
      confounding, being male (adj. OR 1.65; 95%CI 1.03, 2.73), age 25-34 (adj. OR
      0.63; 95% CI 0.40, 0.94) and >=35 years (adj. OR 0.30; 95%CI 0.17, 0.56), being
      previously married (adj. OR 3.22; 95%CI 1.49, 6.98) and previous HIV testing
      (adj. OR 0.50; 95%CI 0.30, 0.74) were significantly associated with HBHCT
      acceptance. Of 408 who took the test, 30 (7.4%, 95% CI: 4.8%- 9.9%) previously
      unknown HIV positive individuals were identified and linked to HIV care.
      CONCLUSIONS: Acceptance of home-based counseling and testing was relatively high
      in this urban setting. This strategy provided access to HIV testing for
      previously untested and unknown HIV-infected individuals in the community. Age,
      sex, marital status and previous HIV test history are important factors that may
      be considered when designing programs for home-based HIV testing in urban
      settings in Uganda.

PMID- 21943165
TI  - Association between copy number variation of complement component C4 and Graves'
      disease.
AB  - BACKGROUND: Gene copy number of complement component C4, which varies among
      individuals, may determine the intrinsic strength of the classical complement
      pathway. Presuming a major role of complement as an effecter in peptide-mediated
      inflammation and phagocytosis, we hypothesized that C4 genetic diversity may
      partially explain the development of Graves' disease (GD) and the variation in
      its outcomes. METHODS: A case-control study including 624 patients with GD and
      160 healthy individuals were enrolled. CNV of C4 isotypes (C4A and C4B) genes
      were performed by quantitative real-time polymerase chain reaction analysis.
      Statistical comparison and identification of CNV of total C4, C4 isotypes (C4A
      and C4B) and C4 polymorphisms were estimated according to the occurrence of GD
      and its associated clinical features. RESULTS: Individuals with 4, 2, and 2
      copies of C4, C4A and C4B genes, especially those with A2B2 polymorphism may
      associate with the development of GD (p = 0.001, OR = 10.994, 95% CI: 6.277
      19.255; p = 0.008, OR = 1.732, 95% CI: 1.190-2.520; p = 2.420 * 10-5, OR = 2.621,
      95% CI: 1.791-3.835; and p = 1.395 * 10-4, OR = 2.671, 95% CI: 1.761-4.052,
      respectively). Although the distribution of copy number for total C4, C4 isotypes
      as well as C4 polymorphisms did not associate with the occurrence of goiter,
      nodular hyperplasia, GO and myxedema, <2 copies of C4A may associate with high
      risk toward vitiligo in patients with GD (p = 0.001, OR = 5.579, 95% CI: 1.659
      18.763). CONCLUSIONS: These results may be further estimated for its clinical
      application on GD and the vitiligo in patients with GD.

PMID- 21943166
TI  - Factor X deficiency and pregnancy: case report and counselling.

PMID- 21943167
TI  - Religion, morality, evolution.
AB  - How did religion evolve? What effect does religion have on our moral beliefs and
      moral actions? These questions are related, as some scholars propose that
      religion has evolved to enhance altruistic behavior toward members of one's
      group. I review here data from survey studies (both within and across countries),
      priming experiments, and correlational studies of the effects of religion on
      racial prejudice. I conclude that religion has powerfully good moral effects and
      powerfully bad moral effects, but these are due to aspects of religion that are
      shared by other human practices. There is surprisingly little evidence for a
      moral effect of specifically religious beliefs.

PMID- 21943169
TI  - Intelligence.
AB  - Individual differences in human intelligence are of interest to a wide range of
      psychologists and to many people outside the discipline. This overview of
      contributions to intelligence research covers the first decade of the twenty
      first century. There is a survey of some of the major books that appeared since
      2000, at different levels of expertise and from different points of view.
      Contributions to the phenotype of intelligence differences are discussed, as well
      as some contributions to causes and consequences of intelligence differences. The
      major causal issues covered concern the environment and genetics, and how
      intelligence differences are being mapped to brain differences. The major
      outcomes discussed are health, education, and socioeconomic status. Aging and
      intelligence are discussed, as are sex differences in intelligence and whether
      twins and singletons differ in intelligence. More generally, the degree to which
      intelligence has become a part of broader research in neuroscience, health, and
      social science is discussed.

PMID- 21943168
TI  - Child development in the context of disaster, war, and terrorism: pathways of
      risk and resilience.
AB  - This review highlights progress over the past decade in research on the effects
      of mass trauma experiences on children and youth, focusing on natural disasters,
      war, and terrorism. Conceptual advances are reviewed in terms of prevailing risk
      and resilience frameworks that guide basic and translational research. Recent
      evidence on common components of these models is evaluated, including dose
      effects, mediators and moderators, and the individual or contextual differences
      that predict risk or resilience. New research horizons with profound implications
      for health and well-being are discussed, particularly in relation to plausible
      models for biological embedding of extreme stress. Strong consistencies are noted
      in this literature, suggesting guidelines for disaster preparedness and response.
      At the same time, there is a notable shortage of evidence on effective
      interventions for child and youth victims. Practical and theory-informative
      research on strategies to protect children and youth victims and promote their
      resilience is a global priority.

PMID- 21943170
TI  - Human intracranial recordings and cognitive neuroscience.
AB  - The ultimate goal of neuroscience research is to understand the operating
      mechanism of the human brain and to exploit this understanding to devise methods
      for repair when it malfunctions. A key feature of this operating mechanism is
      electrical activity of single brain cells and cell assemblies. For obvious
      ethical reasons, scientists rely mostly on animal research in the study of such
      signals. Research in humans is often limited to electrical signals that can be
      recorded at the scalp or to surrogates of electrical activity, namely magnetic
      source imaging and measures of regional blood flow and metabolism. Invasive brain
      recordings performed in patients during various clinical procedures provide a
      unique opportunity to record high-resolution signals in vivo from the human brain
      data that are otherwise unavailable. Of special value are the rare opportunities
      to record in awake humans the activity of single brain cells and small cellular
      assemblies. These recordings provide a unique view on aspects of human cognition
      that are impossible to study in animals, including language, imagery, episodic
      memory, volition, and even consciousness. In the current review we discuss the
      unique contribution of invasive recordings from patients to the field of
      cognitive neuroscience.

PMID- 21943172
TI  - Decoding patterns of human brain activity.
AB  - Considerable information about mental states can be decoded from noninvasive
      measures of human brain activity. Analyses of brain activity patterns can reveal
      what a person is seeing, perceiving, attending to, or remembering. Moreover,
      multidimensional models can be used to investigate how the brain encodes complex
      visual scenes or abstract semantic information. Such feats of "brain reading" or
      "mind reading," though impressive, raise important conceptual, methodological,
      and ethical issues. What does successful decoding reveal about the cognitive
      functions performed by a brain region? How should brain signals be spatially
      selected and mathematically combined to ensure that decoding reflects inherent
      computations of the brain rather than those performed by the decoder? We
      highlight recent advances and describe how multivoxel pattern analysis can
      provide a window into mind-brain relationships with unprecedented specificity,
      when carefully applied. However, as brain-reading technology advances, issues of
      neuroethics and mental privacy will be important to consider.

PMID- 21943174
TI  - Cytometric evaluation of intracellular IFN-gamma and IL-4 levels in thyroid
      follicular cells from patients with autoimmune thyroid diseases.
AB  - BACKGROUND: In recent few years is underlined that altered balance of pro- and
      anti-inflammatory cytokines play an important role in the pathogenesis of
      AITD.The aim of this study was to estimate intracellular INF-gamma and IL-4
      levels in thyroid-infiltrating lymphocytes and thyrocytes isolated from thyroid
      tissues in 54 adolescent patients aged 8-21 years, with Graves' disease (GD; n =
      18), Hashimoto's thyroiditis (HT; n = 18) and non-toxic multinodular goiter
      (NTMG; n = 18). METHODS: Fresh thyroid tissues were taken on culture medium RPMI 
      1640, it was mechanically prepared. In next step were added cell activators -12-
      myristate 13- the acetate (PMA) and Ionomycin as well as the inhibitor of
      transportation of proteins - Breferdin A. They were cultured 24 hours in 50 ml
      flasks at 37 degrees C in a 5-95% CO2-air water-saturated atmosphere. After that,
      thyrocytes were identified by mouse mAb directed against human TPO epitope 64
      conjugated with rabbit anti-mouse antibodies IgG (Fab')2 labeled by FITC. After
      incubation at room temperature to each of samples added reagent A fixative the
      cellular membrane. In next step into the cell suspensions were added reagent B to
      permeabilization of cellular membrane and specific anti-IL-4-PE or anti-IFN-gamma
      PE mAbs. Identification of intracellular cytokines in T lymphocytes was performed
      in the same procedure with application of anti-CD4-PerCP and anti-CD8-PerCP mAbs
      specific for T lymphocytes. The cells were analyzed in a flow cytometry (Coulter
      EPICS XL). RESULTS: In examined group of patients with GD we observed
      statistically significant higher mean percentage of cells with phenotype CD4+IL-4
      (p < 0.05; p < 0.025), CD8+IL-4 (p < 0.033; p < 0.01) and TFCs-IL-4+ (p < 0.05; p
      < 0.01) in comparison to patients with HT and NTMG. The analysis of mean
      percentages of positive TILs and TFCs with intracellular INF-g levels in patients
      with HT revealed statistically significant increase percentage of CD4+INF-gamma
      (p < 0.04; p < 0.001), CD8+ INF-gamma (NS; p < 0.025), TFCs+INF-gamma (p < 0.03;
      p < 0.001) cells in comparison to the percentage of positive cells from patients
      with GD and NTMG. CONCLUSIONS: We conclude that human thyrocytes in autoimmune
      thyroid disorders could be a source of cytokine production and that their
      activation influences local interaction with T lymphocytes inflowing to the
      thyroid gland.

PMID- 21943175
TI  - Intravascular large B-cell lymphoma of the kidney: a case report.
AB  - We report a 41-year-old Chinese woman with intravascular large B-cell lymphoma
      diagnosed by percutaneous renal biopsy. The patient was admitted to Nanfang
      Hospital of Southern Medical University, Guangzhou, China with complaints of high
      spiking fever for a month and bilateral lower limb fatigue with difficulty
      ambulating for the past 5 months.She had renal dysfunction with a total urinary
      protein of 5.61 g/dL (56.1 g/L), serum albumin of 2.89 g/dL (28.9 g/L), urea
      nitrogen of 2.24 mg/dL (1.6 mmol/L), and serum creatinine of 0.54 mg/dL (48
      MUmol/L). Bone marrow biopsy revealed myeloproliferative disorder without
      abnormal myeloid or lymphocytic proliferation. Positron Emission Tomography
      Computed Tomography (PET-CT) showed marked bilateral swelling and enlargement of
      the renal parenchyma with splenic enlargement and involvement of multiple
      vertebrae. Percutaneous renal biopsy showed island-like accumulations of medium
      to large lymphoid cells in many areas of the interstitium, with round vesicular
      nuclei containing distinct basophilic nucleoli. Immunohistochemical analysis
      together with other supportive investigation confirmed the diagnosis of
      intravascular large B-cell lymphoma. Ten days later, she was started on
      chemotherapy with CHOP (cyclophosphamide, doxorubicin, leurocristime and
      prednisone) for a week. Palliative radiotherapy DT 40Gy/20F with other supportive
      treatment was provided for metastatic foci in the medullary cavity of the
      sternum, T1-T7. The patient regained muscle strength in both lower limbs and was
      able to walk again after three weeks. The patient was discharged after hepatic
      and renal function and proteinuria values had returned to normal. Follow-up data
      shows the patient to be alive nine months after discharge.

PMID- 21943171
TI  - Distributed representations in memory: insights from functional brain imaging.
AB  - Forging new memories for facts and events, holding critical details in mind on a
      moment-to-moment basis, and retrieving knowledge in the service of current goals
      all depend on a complex interplay between neural ensembles throughout the brain.
      Over the past decade, researchers have increasingly utilized powerful analytical
      tools (e.g., multivoxel pattern analysis) to decode the information represented
      within distributed functional magnetic resonance imaging activity patterns. In
      this review, we discuss how these methods can sensitively index neural
      representations of perceptual and semantic content and how leverage on the
      engagement of distributed representations provides unique insights into distinct
      aspects of memory-guided behavior. We emphasize that, in addition to
      characterizing the contents of memories, analyses of distributed patterns shed
      light on the processes that influence how information is encoded, maintained, or
      retrieved, and thus inform memory theory. We conclude by highlighting open
      questions about memory that can be addressed through distributed pattern
      analyses.

PMID- 21943176
TI  - A MCP1 fusokine with CCR2-specific tumoricidal activity.
AB  - BACKGROUND: The CCL2 chemokine is involved in promoting cancer angiogenesis,
      proliferation and metastasis by malignancies that express CCR2 receptor. Thus the
      CCL2/CCR2 axis is an attractive molecular target for anticancer drug development.
      METHODS: We have generated a novel fusion protein using GMCSF and an N-terminal
      truncated version of MCP1/CCL2 (6-76) [hereafter GMME1] and investigated its
      utility as a CCR2-specific tumoricidal agent. RESULTS: We found that distinct to
      full length CCL2 or its N-truncated derivative (CCL2 5-76), GMME1 bound to CCR2
      on mouse lymphoma EG7, human multiple myeloma cell line U266, or murine and human
      medulloblastoma cell lines, and led to their death by apoptosis. We demonstrated
      that GMME1 specifically blocked CCR2-associated STAT3 phosphorylation and up
      regulated pro-apoptotic BAX. Furthermore, GMME1 significantly inhibited EG7 tumor
      growth in C57BL/6 mice, and induced apoptosis of primary myeloma cells from
      patients. CONCLUSION: Our data demonstrate that GMME1 is a fusokine with a
      potent, CCR2 receptor-mediated pro-apoptotic effect on tumor cells and could be
      exploited as a novel biological therapy for CCR2+ malignancies including lymphoid
      and central nervous system malignancies.

PMID- 21943177
TI  - Is Drotrecogin alfa (activated) for adults with severe sepsis, cost-effective in
      routine clinical practice?
AB  - INTRODUCTION: Previous cost-effectiveness analyses (CEA) reported that
      Drotrecogin alfa (DrotAA) is cost-effective based on a Phase III clinical trial
      (PROWESS). There is little evidence on whether DrotAA is cost-effective in
      routine clinical practice. We assessed whether DrotAA is cost-effective in
      routine practice for adult patients with severe sepsis and multiple organ systems
      failing. METHODS: This CEA used data from a prospective cohort study that
      compared DrotAA versus no DrotAA (control) for severe sepsis patients with
      multiple organ systems failing admitted to critical care units in England, Wales,
      and Northern Ireland. The cohort study used case-mix and mortality data from a
      national audit, linked with a separate audit of DrotAA infusions. Re-admissions
      to critical care and corresponding mortality were recorded for four years.
      Patients receiving DrotAA (n = 1,076) were matched to controls (n = 1,650) with a
      propensity score (Pscore), and Genetic Matching (GenMatch). The CEA projected
      long-term survival to report lifetime incremental costs per quality-adjusted life
      year (QALY) overall, and for subgroups with two or three to five organ systems
      failing at baseline. RESULTS: The incremental costs per QALY for DrotAA were
      L30,000 overall, and L16,000 for the subgroups with three to five organ systems
      failing. For patients with two organ systems failing, DrotAA resulted in an
      average loss of one QALY at an incremental cost of L15,000. When the subgroup
      with two organ systems was restricted to patients receiving DrotAA within 24
      hours, DrotAA led to a gain of 1.2 QALYs at a cost per QALY of L11,000. The
      results were robust to other assumptions including the approach taken to
      projecting long-term outcomes. CONCLUSIONS: DrotAA is cost-effective in routine
      practice for severe sepsis patients with three to five organ systems failing. For
      patients with two organ systems failing, this study could not provide unequivocal
      evidence on the cost-effectiveness of DrotAA.

PMID- 21943178
TI  - Validation of the UCLA Child Post traumatic stress disorder-reaction index in
      Zambia.
AB  - BACKGROUND: Sexual violence against children is a major global health and human
      rights problem. In order to address this issue there needs to be a better
      understanding of the issue and the consequences. One major challenge in
      accomplishing this goal has been a lack of validated child mental health
      assessments in low-resource countries where the prevalence of sexual violence is
      high. This paper presents results from a validation study of a trauma-focused
      mental health assessment tool - the UCLA Post-traumatic Stress Disorder -
      Reaction Index (PTSD-RI) in Zambia. METHODS: The PTSD-RI was adapted through the
      addition of locally relevant items and validated using local responses to three
      cross-cultural criterion validity questions. Reliability of the symptoms scale
      was assessed using Cronbach alpha analyses. Discriminant validity was assessed
      comparing mean scale scores of cases and non-cases. Concurrent validity was
      assessed comparing mean scale scores to a traumatic experience index. Sensitivity
      and specificity analyses were run using receiver operating curves. RESULTS:
      Analysis of data from 352 youth attending a clinic specializing in sexual abuse
      showed that this adapted PTSD-RI demonstrated good reliability, with Cronbach
      alpha scores greater than .90 on all the evaluated scales. The symptom scales
      were able to statistically significantly discriminate between locally identified
      cases and non-cases, and higher symptom scale scores were associated with
      increased numbers of trauma exposures which is an indication of concurrent
      validity. Sensitivity and specificity analyses resulted in an adequate area under
      the curve, indicating that this tool was appropriate for case definition.
      CONCLUSIONS: This study has shown that validating mental health assessment tools
      in a low-resource country is feasible, and that by taking the time to adapt a
      measure to the local context, a useful and valid Zambian version of the PTSD-RI
      was developed to detect traumatic stress among youth. This valid tool can now be
      used to appropriately measure treatment effectiveness, and more effectively and
      efficiently triage youth to appropriate services.

PMID- 21943179
TI  - Comparison of regression models for estimation of isometric wrist joint torques
      using surface electromyography.
AB  - BACKGROUND: Several regression models have been proposed for estimation of
      isometric joint torque using surface electromyography (SEMG) signals. Common
      issues related to torque estimation models are degradation of model accuracy with
      passage of time, electrode displacement, and alteration of limb posture. This
      work compares the performance of the most commonly used regression models under
      these circumstances, in order to assist researchers with identifying the most
      appropriate model for a specific biomedical application. METHODS: Eleven healthy
      volunteers participated in this study. A custom-built rig, equipped with a torque
      sensor, was used to measure isometric torque as each volunteer flexed and
      extended his wrist. SEMG signals from eight forearm muscles, in addition to wrist
      joint torque data were gathered during the experiment. Additional data were
      gathered one hour and twenty-four hours following the completion of the first
      data gathering session, for the purpose of evaluating the effects of passage of
      time and electrode displacement on accuracy of models. Acquired SEMG signals were
      filtered, rectified, normalized and then fed to models for training. RESULTS: It
      was shown that mean adjusted coefficient of determination (Ra2) values decrease
      between 20%-35% for different models after one hour while altering arm posture
      decreased mean Ra2 values between 64% to 74% for different models. CONCLUSIONS:
      Model estimation accuracy drops significantly with passage of time, electrode
      displacement, and alteration of limb posture. Therefore model retraining is
      crucial for preserving estimation accuracy. Data resampling can significantly
      reduce model training time without losing estimation accuracy. Among the models
      compared, ordinary least squares linear regression model (OLS) was shown to have
      high isometric torque estimation accuracy combined with very short training
      times.

PMID- 21943180
TI  - Moxibustion for cephalic version: a feasibility randomised controlled trial.
AB  - BACKGROUND: Moxibustion (a type of Chinese medicine which involves burning a herb
      close to the skin) has been used to correct a breech presentation. Evidence of
      effectiveness and safety from systematic reviews is encouraging although
      significant heterogeneity has been found among trials. We assessed the
      feasibility of conducting a randomised controlled trial of moxibustion plus usual
      care compared with usual care to promote cephalic version in women with a breech
      presentation, and examined the views of women and health care providers towards
      implementing a trial within an Australian context. METHODS: The study was
      undertaken at a public hospital in Newcastle, New South Wales, Australia. Women
      at 34-36.5 weeks of gestation with a singleton breech presentation (confirmed by
      ultrasound), were randomised to moxibustion plus usual care or usual care alone.
      The intervention was administered over 10 days. Clinical outcomes included
      cephalic presentation at birth, the need for ECV, mode of birth; perinatal
      morbidity and mortality, and maternal complications. Feasibility outcomes
      included: recruitment rate, acceptability, compliance and a sample size for a
      future study. Interviews were conducted with 19 midwives and obstetricians to
      examine the acceptability of moxibustion, and views on the trial. RESULTS: Twenty
      women were randomised to the trial. Fifty one percent of women approached
      accepted randomisation to the trial. A trend towards an increase in cephalic
      version at delivery (RR 5.0; 95% CI 0.7-35.5) was found for women receiving
      moxibustion compared with usual care. There was also a trend towards greater
      success with version following ECV. Two babies were admitted to the neonatal unit
      from the moxibustion group. Compliance with the moxibustion protocol was
      acceptable with no reported side effects. Clinicians expressed the need for
      research to establish the safety and efficacy of moxibustion, and support for the
      intervention was given to increase women's choices, and explore opportunities to
      normalise birth. The sample size for a future trial is estimated to be 381 women.
      CONCLUSION: Our findings should be interpreted with caution as the study was
      underpowered to detect statistical differences between groups. Acceptance by
      women and health professionals towards moxibustion suggest further research is
      warranted. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register
      (ANZCTR): ACTRN12609000985280.

PMID- 21943181
TI  - Phylogenetic relationships within the speciose family Characidae (Teleostei:
      Ostariophysi: Characiformes) based on multilocus analysis and extensive ingroup
      sampling.
AB  - BACKGROUND: With nearly 1,100 species, the fish family Characidae represents more
      than half of the species of Characiformes, and is a key component of Neotropical
      freshwater ecosystems. The composition, phylogeny, and classification of
      Characidae is currently uncertain, despite significant efforts based on analysis
      of morphological and molecular data. No consensus about the monophyly of this
      group or its position within the order Characiformes has been reached, challenged
      by the fact that many key studies to date have non-overlapping taxonomic
      representation and focus only on subsets of this diversity. RESULTS: In the
      present study we propose a new definition of the family Characidae and a
      hypothesis of relationships for the Characiformes based on phylogenetic analysis
      of DNA sequences of two mitochondrial and three nuclear genes (4,680 base pairs).
      The sequences were obtained from 211 samples representing 166 genera distributed
      among all 18 recognized families in the order Characiformes, all 14 recognized
      subfamilies in the Characidae, plus 56 of the genera so far considered incertae
      sedis in the Characidae. The phylogeny obtained is robust, with most lineages
      significantly supported by posterior probabilities in Bayesian analysis, and high
      bootstrap values from maximum likelihood and parsimony analyses. CONCLUSION: A
      monophyletic assemblage strongly supported in all our phylogenetic analysis is
      herein defined as the Characidae and includes the characiform species lacking a
      supraorbital bone and with a derived position of the emergence of the hyoid
      artery from the anterior ceratohyal. To recognize this and several other
      monophyletic groups within characiforms we propose changes in the limits of
      several families to facilitate future studies in the Characiformes and
      particularly the Characidae. This work presents a new phylogenetic framework for
      a speciose and morphologically diverse group of freshwater fishes of significant
      ecological and evolutionary importance across the Neotropics and portions of
      Africa.

PMID- 21943182
TI  - Citation analysis of Australia-trained optometrists.
AB  - Hirsch recently proposed the h-index as a single-number metric to describe the
      impact of an academic, combining quality with quantity. An index of h indicates
      that an individual has h publications, which have been cited at least h times. In
      this paper, the Google Scholar database and Publish or Perish software are used
      to generate citation metrics of Australia-trained optometrists. We conclude that
      this analysis has considerable utility in defining and contextualising the
      general landscape of Australian academic publishing in a national and
      international framework.

PMID- 21943183
TI  - Intensified thermal management for patients undergoing transcatheter aortic valve
      implantation (TAVI).
AB  - BACKGROUND: Transcatheter aortic valve implantation via the transapical approach
      (TAVI-TA) without cardiopulmonary bypass (CPB) is a minimally invasive
      alternative to open-heart valve replacement. Despite minimal exposure and
      extensive draping perioperative hypothermia still remains a problem. METHODS: In
      this observational study, we compared the effects of two methods of thermal
      management on the perioperative course of core temperature. The methods were
      standard thermal management (STM) with a circulating hot water blanket under the
      patient, forced-air warming with a lower body blanket and warmed infused fluids,
      and an intensified thermal management (ITM) with additional prewarming using
      forced-air in the pre-operative holding area on the awake patient. RESULTS:
      Nineteen patients received STM and 20 were treated with ITM. On ICU admission,
      ITM-patients had a higher core temperature (36.4+/-0.7 degrees C vs. 35.5+/-0.9
      degrees C, p=0.001), required less time to achieve normothermia (median (IQR) in
      min: 0 (0-15) vs. 150 (0-300), p=0.003) and a shorter period of ventilatory
      support (median (IQR) in min: 0 (0-0) vs. 246 (0-451), p=0.001). CONCLUSION: ITM
      during TAVI-TA reduces the incidence of hypothermia and allows for faster
      recovery with less need of ventilatory support.

PMID- 21943184
TI  - A way of being: bringing mindfulness into individual therapy.
AB  - This paper reports a qualitative, idiographic study employing Interpretative
      Phenomenological Analysis to explore the experiences of therapists who have a
      mindfulness practice, looking at how this is brought into their individual
      therapeutic work. Findings focus on mindfulness, conceptualized as a way of
      being, which emerges as a central theme in all accounts. Three "way of being"
      related themes are used to illustrate therapists' experiences of mindfulness as
      part of their personal life and how this is brought into the therapy room both
      implicitly and explicitly. The application of mindfulness in therapy is discussed
      while drawing links with the mindfulness literature.

PMID- 21943185
TI  - Yeast processing bodies and stress granules: self-assembly ribonucleoprotein
      particles.
AB  - Processing bodies (PBs) and stress granules (SGs) are two highly conserved
      cytoplasmic ribonucleoprotein foci that contain translationally repressed mRNAs
      together with proteins from the mRNA metabolism. Interestingly, they also share
      some common features with other granules, including the prokaryotic inclusion
      bodies. Although the function of PBs and SGs remains elusive, major advances have
      been done in unraveling their composition and assembly by using the yeast
      Saccharomyces cerevisae.

PMID- 21943187
TI  - Dose-rate effect on proliferation suppression in human cell lines continuously
      exposed to gamma rays.
AB  - Irradiation time and dose rate are important factors in the evaluation of
      radiation risk for human health. We previously proposed a novel dose-rate effect
      model, the modified exponential (MOE) model, which predicts that radiation risks
      decline exponentially as the dose rate decreases. Here we show that, during the
      early phase of exposure, up to 1000 h, the proliferation of cells continuously
      exposed to gamma rays at a constant dose rate is gradually suppressed, even as
      the total dose increases. This trend holds for a number of cell lines including
      tumor cells, nontransformed fibroblasts and leukocytes. The accumulation of total
      dose by longer exposure times does not increase this suppressive effect even in
      cells with a defective DNA repair system, suggesting that risk is determined
      solely by dose rate in the later phase. The dose-rate effect in the early phase
      follows the MOE model in DNA repair-proficient cell lines, while cells with
      impaired DNA-PK or ATM show no dose-rate effect. In the later phase, however, a
      certain dose-rate effect is observed even in mutant cell lines, and suppression
      of cell proliferation no longer follows the MOE model. Our results suggest that a
      distinct mechanism that can operate in the absence of intact DNA-PK or ATM
      influences the dose-rate effect in the later phase of continuous radiation
      exposure.

PMID- 21943186
TI  - TLR4 signalling in pulmonary stromal cells is critical for inflammation and
      immunity in the airways.
AB  - Inflammation of the airways, which is often associated with life-threatening
      infection by Gram-negative bacteria or presence of endotoxin in the bioaerosol,
      is still a major cause of severe airway diseases. Moreover, inhaled endotoxin may
      play an important role in the development and progression of airway inflammation
      in asthma. Pathologic changes induced by endotoxin inhalation include
      bronchospasm, airflow obstruction, recruitment of inflammatory cells, injury of
      the alveolar epithelium, and disruption of pulmonary capillary integrity leading
      to protein rich fluid leak in the alveolar space. Mammalian Toll-like receptors
      (TLRs) are important signalling receptors in innate host defense. Among these
      receptors, TLR4 plays a critical role in the response to endotoxin. Lungs are a
      complex compartmentalized organ with separate barriers, namely the alveolar
      capillary barrier, the microvascular endothelium, and the alveolar epithelium. An
      emerging theme in the field of lung immunology is that structural cells (SCs) of
      the airways such as epithelial cells (ECs), endothelial cells, fibroblasts and
      other stromal cells produce activating cytokines that determine the quantity and
      quality of the lung immune response. This review focuses on the role of TLR4 in
      the innate and adaptive immune functions of the pulmonary SCs.

PMID- 21943190
TI  - Visual function and serous retinal detachment in patients with branch retinal
      vein occlusion and macular edema: a case series.
AB  - BACKGROUND: The influence of serous retinal detachment (SRD) on retinal
      sensitivity in patients with branch retinal vein occlusion (BRVO) and macular
      edema remains unclear. This is despite the frequent co-existence of SRD and
      cystoid macular edema (CME) in BRVO patients on optical coherence tomography
      (OCT) and the fact that CME is the most common form of macular edema secondary to
      BRVO. We investigated visual function (visual acuity and macular sensitivity),
      macular thickness, and macular volume in patients with BRVO and macular edema.
      METHODS: Fifty-three consecutive BRVO patients (26 women and 27 men) were divided
      into two groups based on optical coherence tomography findings. Macular function
      was documented by microperimetry, while macular thickness and volume were
      measured by OCT. RESULTS: There were 15 patients with SRD and 38 patients with
      CME. Fourteen of the 15 patients with SRD also had CME. Visual acuity was
      significantly worse in the SRD group than in the CME group (P = 0.049). Also,
      macular thickness and macular volume within the central 4 degrees , 10 degrees ,
      and 20 degrees  fields were significantly greater in the SRD group (P = 0.008,
      and P = 0.007, P < 0.001 and P < 0.001, and P < 0.001 and P < 0.001,
      respectively). However, macular sensitivity within the central 4 degrees , 10
      degrees , and 20 degrees  fields was not significantly worse in the SRD group
      than in the CME group. CONCLUSIONS: SRD itself may decrease visual acuity
      together with CME, because nearly all SRD patients also had CME. SRD does not
      seem to influence macular function on microperimetry.

PMID- 21943191
TI  - Significant linkage at chromosome 19q for otitis media with effusion and/or
      recurrent otitis media (COME/ROM).
AB  - BACKGROUND: In previous analyses, we identified a region of chromosome 19 as
      harboring a susceptibility locus for chronic otitis media with effusion and/or
      recurrent otitis media (COME/ROM). Our aim was to further localize the linkage
      signal and ultimately identify the causative variant or variants. We followed up
      our previous linkage scan with dense SNP genotyping across in a 5 Mb region. A
      total of 607 individuals from 139 families, including 159 affected sib pairs and
      62 second-degree affected relative pairs, were genotyped at 1,091 SNPs. We
      carried out a nonparametric linkage analysis, modeling marker-to-marker linkage
      disequilibrium. RESULTS: The maximum log of the odds (LOD) score increased to
      3.75 (P = 1.6 * 10(-5)) at position 63.4 Mb, with a LOD-1 support interval
      between 61.6 Mb and 63.8 Mb, providing significant evidence of linkage between
      this region and COME/ROM. The support interval contains over 90 known genes,
      including several genes involved in the inflammasome protein complex, a key
      regulator of the innate immune response to harmful exogenous or endogenous
      stimuli. Parametric linkage analysis suggests that for a sib of an affected
      individual, the recurrence risk of COME/ROM due to this linkage region is twice
      the recurrence risk in the population. We examined potential associations between
      the SNPs genotyped in this region and COME/ROM, however none provided evidence
      for association. CONCLUSION: This study has refined the 19q region of linkage
      with COME/ROM, and association results suggest that the linkage signal may be due
      to rare variants.

PMID- 21943192
TI  - New dystrophin/dystroglycan interactors control neuron behavior in Drosophila
      eye.
AB  - BACKGROUND: The Dystrophin Glycoprotein Complex (DGC) is a large multi-component
      complex that is well known for its function in muscle tissue. When the main
      components of the DGC, Dystrophin (Dys) and Dystroglycan (Dg) are affected
      cognitive impairment and mental retardation in addition to muscle degeneration
      can occur. Previously we performed an array of genetic screens using a Drosophila
      model for muscular dystrophy in order to find novel DGC interactors aiming to
      elucidate the signaling role(s) in which the complex is involved. Since the
      function of the DGC in the brain and nervous system has not been fully defined,
      we have here continued to analyze the DGC modifiers' function in the developing
      Drosophila brain and eye. RESULTS: Given that disruption of Dys and Dg leads to
      improper photoreceptor axon projections into the lamina and eye neuron elongation
      defects during development, we have determined the function of previously
      screened components and their genetic interaction with the DGC in this tissue.
      Our study first found that mutations in chif, CG34400, Nrk, Lis1, capt and Cam
      cause improper axon path-finding and loss of SP2353, Grh, Nrk, capt, CG34400,
      vimar, Lis1 and Cam cause shortened rhabdomere lengths. We determined that Nrk,
      mbl, capt and Cam genetically interact with Dys and/or Dg in these processes. It
      is notable that most of the neuronal DGC interacting components encountered are
      involved in regulation of actin dynamics. CONCLUSIONS: Our data indicate possible
      DGC involvement in the process of cytoskeletal remodeling in neurons. The
      identification of new components that interact with the DGC not only helps to
      dissect the mechanism of axon guidance and eye neuron differentiation but also
      provides a great opportunity for understanding the signaling mechanisms by which
      the cell surface receptor Dg communicates via Dys with the actin cytoskeleton.

PMID- 21943193
TI  - Understanding FVIII/VWF complex--report from a symposium of XXIX WFH meeting
      2010.
AB  - von Willebrand factor (VWF) has the capacity to form a complex with factor VIII
      (FVIII) which may modulate the immunogenicity of FVIII. It has been proposed that
      a significant fraction of recombinant FVIII (rFVIII) is unable to bind VWF. In an
      experimental model studied at the McMaster University in Canada, this VWF-unbound
      rFVIII fraction showed no coagulant function. Sulphation of FVIII tyrosine (Tyr)
      1680 has been reported as essential for the interaction with VWF. In a study
      performed at the Grifols and CNS-CSIC in Spain, Tyr1680 sulphation was observed
      to be incomplete in rFVIII and complete in plasma-derived FVIII (pdFVIII). This
      could explain the incapability of some rFVIII molecules to bind VWF. Experience
      with immune tolerance induction (ITI) at the Bonn Haemophilia Centre indicates
      that only eradication of FVIII inhibitors allows safe haemostasis control and the
      option of prophylactic treatment. Various clinical trials were planned to
      evaluate the clinical role VWF-containing FVIII concentrates (FVIII/VWF).
      RES.I.ST (an acronym for REScue Immunotolerance STudy) is an international,
      prospective study aimed at assessing whether FVIII/VWF can induce ITI in high
      risk haemophilia patients (RES.I.ST naive) and whether patients who previously
      failed ITI with FVIII alone can be rescued with FVIII/VWF (RES.I.ST experienced).
      Enrolment started in November 2009. In the FAIReSt.Will (Fanhdi and Alphanate
      Italian Retrospective Study in Willebrand disease) study, 120 von Willebrand
      disease (VWD) patients treated with Fanhdi((r)) or Alphanate((r)) were
      retrospectively analysed. Efficacy was excellent and no side effects were
      reported. The ongoing PRO.Will study is a prospective, multicenter trial aimed at
      assessing the efficacy, safety and pharmacoeconomics of secondary long-term
      prophylaxis in patients with severe inherited VWD.

PMID- 21943194
TI  - Secular trends: a ten-year comparison of the amount and type of physical activity
      and inactivity of random samples of adolescents in the Czech Republic.
AB  - BACKGROUND: An optimal level of physical activity (PA) in adolescence influences
      the level of PA in adulthood. Although PA declines with age have been
      demonstrated repeatedly, few studies have been carried out on secular trends. The
      present study assessed levels, types and secular trends of PA and sedentary
      behaviour of a sample of adolescents in the Czech Republic. METHODS: The study
      comprised two cross-sectional cohorts of adolescents ten years apart. The
      analysis compared data collected through a week-long monitoring of adolescents'
      PA in 1998-2000 and 2008-2010. Adolescents wore either Yamax SW-701 or Omron HJ
      105 pedometer continuously for 7 days (at least 10 hours per day) excluding
      sleeping, hygiene and bathing. They also recorded their number of steps per day,
      the type and duration of PA and sedentary behaviour (in minutes) on record
      sheets. In total, 902 adolescents (410 boys; 492 girls) aged 14-18 were eligible
      for analysis. RESULTS: Overweight and obesity in Czech adolescents participating
      in this study increased from 5.5% (older cohort, 1998-2000) to 10.4% (younger
      cohort, 2008-2010). There were no inter-cohort significant changes in the total
      amount of sedentary behaviour in boys. However in girls, on weekdays, there was a
      significant increase in the total duration of sedentary behaviour of the younger
      cohort (2008-2010) compared with the older one (1998-2000). Studying and screen
      time (television and computer) were among the main sedentary behaviours in Czech
      adolescents. The types of sedentary behaviour also changed: watching TV (1998
      2000) was replaced by time spent on computers (2008-2010).The Czech health
      related criterion (achieving 11,000 steps per day) decreased only in boys from
      68% (1998-2000) to 55% (2008-2010). Across both genders, 55%-75% of Czech
      adolescents met the health-related criterion of recommended steps per day,
      however less participants in the younger cohort (2008-2010) met this criterion
      than in the older cohort (1998-2000) ten years ago. Adolescents' PA levels for
      the monitored periods of 1998-2000 and 2008-2010 suggest a secular decrease in
      the weekly number of steps achieved by adolescent boys and girls. CONCLUSION: In
      the younger cohort (2008-2010), every tenth adolescent was either overweight or
      obese; roughly twice the rate when compared to the older cohort (1998-2000).
      Sedentary behaviour seems relatively stable across the two cohorts as the
      increased time that the younger cohort (2008-2010) spent on computers is
      compensated with an equally decreased time spent watching TV or studying. Across
      both cohorts about half to three quarters of the adolescents met the health
      related criterion for achieved number of steps. The findings show a secular
      decrease in PA amongst adolescents. The significant interaction effects (cohort *
      age; and cohort * gender) that this study found suggested that secular trends in
      PA differ by age and gender.

PMID- 21943196
TI  - Using the needs of WHO to prioritise Cochrane reviews: The case of antipsychotic
      drugs.
AB  - BACKGROUND: This study aimed to investigate existing trialling activity relating
      to three antipsychotic drugs from the WHO List of Essential Medicines
      (chlorpromazine, fluphenazine decanoate, haloperidol), link existing trials to
      existing Cochrane reviews, identify gaps in reviewing activity on accessible
      treatments for people with schizophrenia. METHODS: We used the Cochrane
      Schizophrenia Group's register searching for all studies comparing the three
      antipsychotic drugs with each other and with all other pharmacological
      interventions listed on the Essential Medicines List (with the addition of
      'placebo or no drug'). For each we also considered studies that focussed on
      administration, dose, withdrawal and use of that drug in specific circumstances
      administration. Data were then extracted on a number of studies, number of
      participants within those studies, and as to whether a maintained review already
      exists. Finally, every effort was made to consider as to whether there were
      possibilities for missing comparisons that no one had ever investigated. RESULTS:
      There has been considerable research activity involving the three 'essential'
      antipsychotics and also comparing those three drugs to others on the 'essential'
      list. We found 490 studies with 77957 participants for haloperidol, 316 studies
      with 29179 participants for chlorpromazine and 33 studies with 4503 participants
      for fluphenazine decanoate. Reviewing activity has also been considerable in this
      area but there are notable omissions which would necessitate new reviews to
      comprehensively cover the area. CONCLUSIONS: We have used the 'sample frame' of
      the WHO Essential drug list as a starting point. WHO prioritises for us those
      drugs that have universal accessibility but they may not be the compounds that
      are first choice if others are available. It is encouraging to see how many
      maintained reviews already exist to service those undertaking WHO guidelines. The
      needs of those guiding care can be taken as a means of prioritising research. For
      largest global impact WHO Essential Medicine list provides clear direction. By
      using this technique workload can be anticipated, prioritising can take place for
      new reviews and updates.

PMID- 21943195
TI  - Enhanced self-renewal of hematopoietic stem/progenitor cells mediated by the stem
      cell gene Sall4.
AB  - BACKGROUND: Sall4 is a key factor for the maintenance of pluripotency and self
      renewal of embryonic stem cells (ESCs). Our previous studies have shown that
      Sall4 is a robust stimulator for human hematopoietic stem and progenitor cell
      (HSC/HPC) expansion. The purpose of the current study is to further evaluate how
      Sall4 may affect HSC/HPC activities in a murine system. METHODS: Lentiviral
      vectors expressing Sall4A or Sall4B isoform were used to transduce mouse bone
      marrow Lin-/Sca1+/c-Kit+ (LSK) cells and HSC/HPC self-renewal and differentiation
      were evaluated. RESULTS: Forced expression of Sall4 isoforms led to sustained ex
      vivo proliferation of LSK cells. In addition, Sall4 expanded HSC/HPCs exhibited
      increased in vivo repopulating abilities after bone marrow transplantation. These
      activities were associated with dramatic upregulation of multiple HSC/HPC
      regulatory genes including HoxB4, Notch1, Bmi1, Runx1, Meis1 and Nf-ya.
      Consistently, downregulation of endogenous Sall4 expression led to reduced LSK
      cell proliferation and accelerated cell differentiation. Moreover, in myeloid
      progenitor cells (32D), overexpression of Sall4 isoforms inhibited granulocytic
      differentiation and permitted expansion of undifferentiated cells with defined
      cytokines, consistent with the known functions of Sall4 in the ES cell system.
      CONCLUSION: Sall4 is a potent regulator for HSC/HPC self-renewal, likely by
      increasing self-renewal activity and inhibiting differentiation. Our work
      provides further support that Sall4 manipulation may be a new model for expanding
      clinically transplantable stem cells.

PMID- 21943197
TI  - Membrane connectivity estimated by digital image analysis of HER2
      immunohistochemistry is concordant with visual scoring and fluorescence in situ
      hybridization results: algorithm evaluation on breast cancer tissue microarrays.
AB  - INTRODUCTION: The human epidermal growth factor receptor 2 (HER2) is an
      established biomarker for management of patients with breast cancer. While
      conventional testing of HER2 protein expression is based on semi-quantitative
      visual scoring of the immunohistochemistry (IHC) result, efforts to reduce inter
      observer variation and to produce continuous estimates of the IHC data are
      potentiated by digital image analysis technologies. METHODS: HER2 IHC was
      performed on the tissue microarrays (TMAs) of 195 patients with an early ductal
      carcinoma of the breast. Digital images of the IHC slides were obtained by Aperio
      ScanScope GL Slide Scanner. Membrane connectivity algorithm (HER2-CONNECT,
      Visiopharm) was used for digital image analysis (DA). A pathologist evaluated the
      images on the screen twice (visual evaluations: VE1 and VE2). HER2 fluorescence
      in situ hybridization (FISH) was performed on the corresponding sections of the
      TMAs. The agreement between the IHC HER2 scores, obtained by VE1, VE2, and DA was
      tested for individual TMA spots and patient's maximum TMA spot values (VE1max,
      VE2max, DAmax). The latter were compared with the FISH data. Correlation of the
      continuous variable of the membrane connectivity estimate with the FISH data was
      tested. RESULTS: The pathologist intra-observer agreement (VE1 and VE2) on HER2
      IHC score was almost perfect: kappa 0.91 (by spot) and 0.88 (by patient). The
      agreement between visual evaluation and digital image analysis was almost perfect
      at the spot level (kappa 0.86 and 0.87, with VE1 and VE2 respectively) and at the
      patient level (kappa 0.80 and 0.86, with VE1max and VE2max, respectively). The DA
      was more accurate than VE in detection of FISH-positive patients by recruiting 3
      or 2 additional FISH-positive patients to the IHC score 2+ category from the IHC
      0/1+ category by VE1max or VE2max, respectively. The DA continuous variable of
      the membrane connectivity correlated with the FISH data (HER2 and CEP17 copy
      numbers, and HER2/CEP17 ratio). CONCLUSION: HER2 IHC digital image analysis based
      on membrane connectivity estimate was in almost perfect agreement with the visual
      evaluation of the pathologist and more accurate in detection of HER2 FISH
      positive patients. Most immediate benefit of integrating the DA algorithm into
      the routine pathology HER2 testing may be obtained by alerting/reassuring
      pathologists of potentially misinterpreted IHC 0/1+ versus 2+ cases.

PMID- 21943198
TI  - The HIV-1 gp120/V3 modifies the response of uninfected CD4 T cells to antigen
      presentation: mapping of the specific transcriptional signature.
AB  - BACKGROUND: The asymptomatic phase of HIV-1 infection is characterized by a
      progressive depletion of uninfected peripheral effector/memory CD4+ T cells that
      subsequently leads to immune dysfunction and AIDS symptoms. We have previously
      demonstrated that the presence of specific gp120/V3 peptides during antigen
      presentation can modify the activation of normal T-cells leading to altered
      immune function. The aim of the present study was to map the specific
      transcriptional profile invoked by an HIV-1/V3 epitope in uninfected T cells
      during antigen presentation. METHODS: We exposed primary human peripheral blood
      monocytes to V3 lipopeptides using a liposome delivery system followed by a
      superantigen-mediated antigen presentation system. We then evaluated the changes
      in the T-cell transcriptional profile using oligonucleotide microarrays and
      performed Ingenuity Pathway Analysis (IPA) and DAVID analysis. The results were
      validated using realtime PCR, FACS, Western blotting and immunofluorescence.
      RESULTS: Our results revealed that the most highly modulated transcripts could
      almost entirely be categorized as related to the cell cycle or transcriptional
      regulation. The most statistically significant enriched categories and networks
      identified by IPA were associated with cell cycle, gene expression, immune
      response, infection mechanisms, cellular growth, proliferation and antigen
      presentation. Canonical pathways involved in energy and cell cycle regulation,
      and in the co-activation of T cells were also enriched. CONCLUSIONS: Taken
      together, these results document a distinct transcriptional profile invoked by
      the HIV-1/V3 epitope. These data could be invaluable to determine the underlying
      mechanism by which HIV-1 epitopes interfere with uninfected CD4+ T-cell function
      causing hyper proliferation and AICD.

PMID- 21943199
TI  - A palatable hyperlipidic diet causes obesity and affects brain glucose metabolism
      in rats.
AB  - BACKGROUND: We have previously shown that either the continuous intake of a
      palatable hyperlipidic diet (H) or the alternation of chow (C) and an H diet (CH
      regimen) induced obesity in rats. Here, we investigated whether the time of the
      start and duration of these feeding regimens are relevant and whether they affect
      brain glucose metabolism. METHODS: Male Wistar rats received C, H, or CH diets
      during various periods of their life spans: days 30-60, days 30-90, or days 60
      90. Experiments were performed the 60th or the 90th day of life. Rats were killed
      by decapitation. The glucose, insulin, leptin plasma concentration, and lipid
      content of the carcasses were determined. The brain was sliced and incubated with
      or without insulin for the analysis of glucose uptake, oxidation, and the
      conversion of [1-14C]-glucose to lipids. RESULTS: The relative carcass lipid
      content increased in all of the H and CH groups, and the H30-60 and H30-90 groups
      had the highest levels. Groups H30-60, H30-90, CH30-60, and CH30-90 exhibited a
      higher serum glucose level. Serum leptin increased in all H groups and in the
      CH60-90 and CH30-90 groups. Serum insulin was elevated in the H30-60, H60-90,
      CH60-90, CH30-90 groups. Basal brain glucose consumption and hypothalamic insulin
      receptor density were lower only in the CH30-60 group. The rate of brain
      lipogenesis was increased in the H30-90 and CH30-90 groups. CONCLUSION: These
      findings indicate that both H and CH diet regimens increased body adiposity
      independent treatment and the age at which treatment was started, whereas these
      diets caused hyperglycemia and affected brain metabolism when started at an early
      age.

PMID- 21943200
TI  - Antiproliferative effect of methanolic extraction of tualang honey on human
      keloid fibroblasts.
AB  - BACKGROUND: Keloid is a type of scar which extends beyond the boundaries of the
      original wound. It can spread to the surrounding skin by invasion. The use of
      Tualang honey is a possible approach for keloid treatment. The objective of this
      study was to determine the antiproliferative effect of methanolic extraction of
      Tualang honey to primary human keloid fibroblasts and to identify the volatile
      compounds in methanol extraction of Tualang honey. METHODS: Crude Tualang honey
      was extracted with methanol and then dried using rota vapor to remove remaining
      methanol from honey. Normal and keloid fibroblasts were verified and treated with
      the extracted honey. Cell proliferation was tested with [3-(4,5-dimethylthiazol-2
      yi)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt]
      (MTS) assay. Extraction of Tualang honey using methanol was carried out and the
      extracted samples were analysed using gas chromatography-mass spectrometry (GC
      MS). The result was analysed using SPSS and tested with Kruskal-Wallis and Mann
      Whitney tests. RESULTS: Methanolic extraction of honey has positive anti
      proliferative effect on keloid fibroblasts in a dose-dependent manner. The
      presence of fatty acids such as palmitic acid, stearic acid, oleic acid, linoleic
      acid and octadecanoic acid may contribute to the anti-proliferative effect in
      keloid fibroblasts. CONCLUSIONS: The methanolic honey extraction has an
      antiproliferative effect on keloid fibroblasts and a range of volatile compounds
      has been identified from Tualang honey. The antiproliferative effect of keloid
      fibroblasts towards Tualang honey may involve cell signaling pathway. Identifying
      other volatile compounds from different organic solvents should be carried out in
      future.

PMID- 21943201
TI  - A systems-biology approach to understanding the ciliopathy disorders.
AB  - 'Ciliopathies' are an emerging class of genetic multisystemic human disorders
      that are caused by a multitude of largely unrelated genes that affect ciliary
      structure/function. They are unified by shared clinical features, such as mental
      retardation, cystic kidney, retinal defects and polydactyly, and by the common
      localization of the protein products of these genes at or near the primary cilium
      of cells. With the realization that many previously disparate conditions are a
      part of this spectrum of disorders, there has been tremendous interest in the
      function of cilia in developmental signaling and homeostasis. Ciliopathies are
      mostly inherited as simple recessive traits, but phenotypic expressivity is under
      the control of numerous genetic modifiers, putting these conditions at the
      interface of simple and complex genetics. In this review, we discuss the ever
      expanding ciliopathy field, which has three interrelated goals: developing a
      comprehensive understanding of genes mutated in the ciliopathies and required for
      ciliogenesis; understanding how the encoded proteins work together in complexes
      and networks to modulate activity and structure-function relationships; and
      uncovering signaling pathways and modifier relationships.

PMID- 21943202
TI  - Fusion with extracellular domain of cytotoxic T-lymphocyte-associated-antigen 4
      leads to enhancement of immunogenicity of Hantaan virus DNA vaccines in C57BL/6
      mice.
AB  - BACKGROUND: Hantaan virus (HTNV) is the causative agent of the most severe form
      of a rodent-borne disease known as hemorrhagic fever with renal syndrome (HFRS).
      A safe and effective HTNV vaccine is needed. Vaccination with DNA constructs
      expressing fused antigen with bioactive factors, has shown promising improvement
      of immunogenicity for viral agents in animal models, but the effect of fusion
      strategy on HTNV DNA vaccine has not been investigated. RESULTS: DNA plasmids
      encoding the HTNV nucleocapsid protein (N) and glycoprotein (Gn and Gc) in fusion
      to the extracellular domain of cytotoxic T-lymphocyte-associated-antigen 4 (eCTLA
      4) targeting to antigen presenting cells (APCs) were constructed. Intramuscular
      immunization of mice with plasmids expressing eCTLA-4-HTNV-N/GP fusion proteins
      leads to a significant enhancement of the specific antibody response as well as
      cytotoxic T-lymphocyte (CTL) response in C57BL/6 mice. Moreover, this effect
      could be further augmented when co-administered with CpG motifs. CONCLUSIONS:
      Modification of viral antigen in fusion to bioactive factor will be promising to
      confer efficient antigen presentation and improve the potency of DNA vaccine in
      mice.

PMID- 21943204
TI  - High mTOR expression is associated with a worse oncological outcome in laryngeal
      carcinoma treated with postoperative radiotherapy: a pilot study.
AB  - BACKGROUND: There are currently no clinical or pathological parameters able to
      predict response to adjuvant radiotherapy (RT) in laryngeal squamous cell
      carcinoma (LSCC). Few studies have investigated the molecular pathways
      potentially capable of predicting said response. The mammalian target of
      rapamycin (mTOR) acts as a 'master switch' protein in cancer cells, modulating
      metabolism, the cell cycle, and apoptosis. Cancer treatment with mTOR inhibitors
      (rapamycin analogs, or rapalogs) has produced promising results in various
      malignancies (renal cell carcinoma, breast cancer, prostate cancer, leukemia,
      lymphoma, and melanoma). The novel aim of the present study was to ascertain the
      prognostic role of mTOR expression in a series of patients with LSCC treated with
      primary surgery followed by RT. METHODS: The retrospective study involved 25
      consecutive patients with LSCC given postoperative RT. Immunohistochemical mTOR
      expression was evaluated in primary LSCC by image analysis. RESULTS: The
      locoregional recurrence rate was significantly higher in patients with LSCC whose
      mTOR expression was >2.5% (P = 0.013). After postoperative RT, the locoregional
      recurrence risk ratio was 3.25 in LSCCs with mTOR >2.5%. The different disease
      free survival was significantly shorter in cases of LSCC with mTOR >2.5% (P =
      0.029). CONCLUSIONS: mTOR should be studied as a potential predictor for
      identifying LSCCs at higher risk of early recurrence after postoperative RT. New
      therapeutic strategies should be investigated in LSCC, including the use of
      rapalogs associated with conventional chemotherapeutic regimens in combination
      with RT.

PMID- 21943203
TI  - IFN-gamma, IL-17 and TGF-beta involvement in shaping the tumor microenvironment:
      The significance of modulating such cytokines in treating malignant solid tumors.
AB  - Multiple innate and adaptive immune effector cells and molecules partake in the
      recognition and destruction of cancer cells to protect against growing tumors, a
      concept that is known as cancer immunosurveillance. Unfortunately, cancer cells
      are capable of avoiding this process by immunoselection of poorly immunogenic
      tumor cells variants along with subversion of the immune system and thus shaping
      both the tumor and its microenvironment. Cytokines represent part of the complex
      pattern of the immune response which can assist the development of cancer as well
      as to eliminate it. Simultaneously, a large number of cytokines may be involved
      in the complex interactions between host and tumor cells where this dynamic cross
      talk, between tumors and the immune system, can either regulate tumor growth or
      tumor growth, invasion and metastasis take place. In this review, we are
      stressing on the interface between infiltrated immune cells and tumor cells with
      the emphasis on the bidirectional activities of specific cytokines: IFN-gamma,
      TGF-beta and IL-17 within the tumor microenvironment and their role in shaping
      it. In addition, the significance of modulating such cytokines in favor of anti
      tumor response is discussed and merits the use of mixture of targeted modulators
      to overcome the network complexity of cytokines in the tumor microenvironment.

PMID- 21943205
TI  - A simplified clinical prediction score of chronic kidney disease: a cross
      sectional-survey study.
AB  - BACKGROUND: Knowing the risk factors of CKD should be able to identify at risk
      populations. We thus aimed to develop and validate a simplified clinical
      prediction score capable of indicating those at risk. METHODS: A community-based
      cross-sectional survey study was conducted. Ten provinces and 20 districts were
      stratified-cluster randomly selected across four regions in Thailand and Bangkok.
      The outcome of interest was chronic kidney disease stage I to V versus non-CKD.
      Logistic regression was applied to assess the risk factors. Scoring was created
      using odds ratios of significant variables. The ROC curve analysis was used to
      calibrate the cut-off of the scores. Bootstrap was applied to internally validate
      the performance of this prediction score. RESULTS: Three-thousand, four-hundred
      and fifty-nine subjects were included to derive the prediction scores. Four
      (i.e., age, diabetes, hypertension, and history of kidney stones) were
      significantly associated with the CKD. Total scores ranged from 4 to 16 and the
      score discrimination was 77.0%. The scores of 4-5, 6-8, 9-11, and >= 12
      correspond to low, intermediate-low, intermediate-high, and high probabilities of
      CKD with the likelihood ratio positive (LR+) of 1, 2.5 (95% CI: 2.2-2.7), 4.9
      (95% CI: 3.9 - 6.3), and 7.5 (95% CI: 5.6 - 10.1), respectively. Internal
      validity was performed using 200 repetitions of a bootstrap technique.
      Calibration was assessed and the difference between observed and predicted values
      was 0.045. The concordance C statistic of the derivative and validated models
      were similar, i.e., 0.770 and 0.741. CONCLUSIONS: A simplified clinical
      prediction score for estimating risk of having CKD was created. The prediction
      score may be useful in identifying and classifying at riskpatients. However,
      further external validation is needed to confirm this.

PMID- 21943206
TI  - Thoracoscopic resection of thoracic esophageal duplication cyst containing
      ectopic pancreatic tissue in adult.
AB  - Esophageal duplication cyst is a rare congenital anomaly. They can be associated
      with other congenital anomalies, such as spinal abnormalities, and
      tracheoesophageal fistulas. In adults, almost of the patients with esophageal
      duplication cyst is asymptomatic and accidentally diagnosed by chest X-ray or
      computed tomography. However, cysts may become symptomatic owing to complications
      such as esophageal stenosis, respiratory system compression, rupture, infarction,
      or malignancy. Complete surgical resection is the standard treatment even in
      patients with asymptomatic cysts. Traditional approach for resection is via
      thoracotomy. But, the thoracoscopic approach makes more indicate for mediastinal
      diseases, because of minimally invasive for patients. We describe a case with
      esophageal duplication cyst, which contained the ectopic pancreatic tissue in the
      solid portion, resected under the thoracoscopic approach in adult.

PMID- 21943207
TI  - Effectiveness of proactive telephone counselling for smoking cessation in
      parents: study protocol of a randomized controlled trial.
AB  - BACKGROUND: Smoking is the world's fourth most common risk factor for disease,
      the leading preventable cause of death, and it is associated with tremendous
      social costs. In the Netherlands, the smoking prevalence rate is high. A total of
      27.7% of the population over age 15 years smokes. In addition to the direct
      advantages of smoking cessation for the smoker, parents who quit smoking may also
      decrease their children's risk of smoking initiation. METHODS/DESIGN: A
      randomized controlled trial will be conducted to evaluate the effectiveness of
      proactive telephone counselling to increase smoking cessation rates among smoking
      parents. A total of 512 smoking parents will be proactively recruited through
      their children's primary schools and randomly assigned to either proactive
      telephone counselling or a control condition. Proactive telephone counselling
      will consist of up to seven counsellor-initiated telephone calls (based on
      cognitive-behavioural skill building and Motivational Interviewing), distributed
      over a period of three months. Three supplementary brochures will also be
      provided. In the control condition, parents will receive a standard brochure to
      aid smoking cessation. Assessments will take place at baseline, three months
      after start of the intervention (post-measurement), and twelve months after start
      of the intervention (follow-up measurement). Primary outcome measures will
      include sustained abstinence between post-measurement and follow-up measurement
      and 7-day point prevalence abstinence and 24-hours point prevalence abstinence at
      both post- and follow-up measurement. Several secondary outcome measures will
      also be included (e.g., smoking intensity, smoking policies at home). In
      addition, we will evaluate smoking-related cognitions (e.g., attitudes towards
      smoking, social norms, self-efficacy, intention to smoke) in 9-12 year old
      children of smoking parents. DISCUSSION: This study protocol describes the design
      of a randomized controlled trial to evaluate the effectiveness of proactive
      telephone counselling in smoking cessation. It is expected that, in the telephone
      counseling condition, parental smoking cessation rates will be higher and
      children's cognitions will be less favorable about smoking compared to the
      control condition. TRIAL REGISTRATION: The protocol for this study is registered
      with the Netherlands Trial Register NTR2707.

PMID- 21943209
TI  - Off-pump myocardial revascularization in a patient with haemophilia A: a case
      report and operative strategies.

PMID- 21943208
TI  - Cerebrovascular reactivity among native-raised high altitude residents: an fMRI
      study.
AB  - BACKGROUND: The impact of long term residence on high altitude (HA) on human
      brain has raised concern among researchers in recent years. This study
      investigated the cerebrovascular reactivity among native-born high altitude (HA)
      residents as compared to native sea level (SL) residents. The two groups were
      matched on the ancestral line, ages, gender ratios, and education levels. A
      visual cue guided maximum inspiration task with brief breath holding was
      performed by all the subjects while Blood-Oxygenation-Level-Dependent (BOLD)
      functional Magnetic Resonance Imaging (fMRI) data were acquired from them.
      RESULTS: Compared to SL controls, the HA group showed generally decreased
      cerebrovascular reactivity and longer delay in hemodynamic response. Clusters
      showing significant differences in the former aspect were located at the
      bilateral primary motor cortex, the right somatosensory association cortex, the
      right thalamus and the right caudate, the bilateral precuneus, the right
      cingulate gyrus and the right posterior cingulate cortex, as well as the left
      fusiform gyrus and the right lingual cortex; clusters showing significant
      differences in the latter aspect were located at the precuneus, the insula, the
      superior frontal and temporal gyrus, the somatosensory cortex (the postcentral
      gyrus) and the cerebellar tonsil. Inspiratory reserve volume (IRV), which is an
      important aspect of pulmonary function, demonstrated significant correlation with
      the amount of BOLD signal change in multiple brain regions, particularly at the
      bilateral insula among the HA group. CONCLUSIONS: Native-born HA residents
      generally showed reduced cerebrovascular reactivity as demonstrated in the
      hemodynamic response during a visual cue guided maximum inspiration task
      conducted with BOLD-fMRI. This effect was particularly manifested among brain
      regions that are typically involved in cerebral modulation of respiration.

PMID- 21943210
TI  - Profibrotic potential of prominin-1+ epithelial progenitor cells in pulmonary
      fibrosis.
AB  - BACKGROUND: In idiopathic pulmonary fibrosis loss of alveolar epithelium induces
      inflammation of the pulmonary tissue followed by accumulation of pathogenic
      myofibroblasts leading eventually to respiratory failures. In animal models
      inflammatory and resident cells have been demonstrated to contribute to pulmonary
      fibrosis. Regenerative potential of pulmonary and extra-pulmonary stem and
      progenitor cells raised the hope for successful treatment option against
      pulmonary fibrosis. Herein, we addressed the contribution of lung
      microenvironment and prominin-1(+) bone marrow-derived epithelial progenitor
      cells in the mouse model of bleomycin-induced experimental pulmonary fibrosis.
      METHODS: Prominin-1(+) bone marrow-derived epithelial progenitors were expanded
      from adult mouse lungs and differentiated in vitro by cytokines and growth
      factors. Pulmonary fibrosis was induced in C57Bl/6 mice by intratracheal
      instillation of bleomycin. Prominin-1(+) progenitors were administered
      intratracheally at different time points after bleomycin challenge. Green
      fluorescence protein-expressing cells were used for cell tracking. Cell
      phenotypes were characterized by immunohistochemistry, flow cytometry and
      quantitative reverse transcription-polymerase chain reaction. RESULTS: Prominin
      1(+) cells expanded from healthy lung represent common progenitors of alveolar
      type II epithelial cells, myofibroblasts, and macrophages. Administration of
      prominin-1(+) cells 2 hours after bleomycin instillation protects from pulmonary
      fibrosis, and some of progenitors differentiate into alveolar type II epithelial
      cells. In contrast, prominin-1(+) cells administered at day 7 or 14 lose their
      protective effects and differentiate into myofibroblasts and macrophages.
      Bleomycin challenge enhances accumulation of bone marrow-derived prominin-1(+)
      cells within inflamed lung. In contrast to prominin-1(+) cells from healthy lung,
      prominin-1(+) precursors isolated from inflamed organ lack regenerative
      properties but acquire myofibroblast and macrophage phenotypes. CONCLUSION: The
      microenvironment of inflamed lung impairs the regenerative capacity of bone
      marrow-derived prominin-1(+) progenitors and promotes their differentiation into
      pathogenic phenotypes.

PMID- 21943211
TI  - Social capital and AIDS-resilient communities: strengthening the AIDS response.
AB  - This article argues that an effective AIDS response must expand the biomedical
      and individual behaviour frames to include structural interventions that create
      circumstances that enable behavioural change and strengthen communities' own
      efforts to address prevention and treatment. How can the emergence of AIDS
      resilient communities be supported? The article underscores the importance of
      cultural and sociological variables in shaping effective responses to HIV and
      AIDS; social, political and environmental circumstances can facilitate or impede
      behavioural choices and can strengthen or remove barriers to HIV-resilient
      actions. A 'social capital lens' brings into sharp relief how culture, context,
      power relations, the distribution of social and natural resources, vulnerability
      and marginalisation all play a role in shaping options, behaviour and practices.
      Using this lens will give us a better understanding of the complex networks of
      factors influencing human behaviours and social practices and allows us to better
      support the emergence of AIDS-resilient communities and health-enabling
      environments.

PMID- 21943212
TI  - Fluorescence microscope (Cyscope) for malaria diagnosis in pregnant women in
      Medani Hospital, Sudan.
AB  - BACKGROUND: Accuracy of diagnosis is the core for malaria control. Although
      microscopy is the gold standard in malaria diagnosis, its reliability is largely
      dependent on user skill. We compared performance of Cyscope fluorescence
      microscope with the Giemsa stained light microscopy for the diagnosis of malaria
      among pregnant women at Medani Hospital in Central Sudan. The area is
      characterized by unstable malaria transmission. METHODS: Socio-demographic
      characteristics and obstetrics history were gathered using pre-tested
      questionnaires. Blood samples were collected from febrile pregnant women who were
      referred as malaria case following initial diagnosis by general microscopist.
      RESULTS: During the study period 128 febrile pregnant women presented at the
      hospital. Among them, Plasmodium falciparum malaria was detected in 82 (64.1%)
      and 80 (62.5%) by the Giemsa-stained light microscopy and the Cyscope
      fluorescence microscope, respectively. The sensitivity of the Cyscope
      fluorescence microscope was 97.6% (95% CI: 92.2%-99.6%). Out of 46 which were
      negative by Giemsa-stained light microscopy, 5 were positive by the Cyscope
      fluorescence microscope. This is translated in specificity of 89.1% (95% CI:
      77.5%-95.9%). The positive and negative predictive value of Cyscope fluorescence
      microscope was 94.1% (95% CI: 87.4% -97.8%) and 95.3% (95% CI: 85.4% - 99.2%),
      respectively. CONCLUSION: This study has shown that Cyscope fluorescence
      microscope is a reliable diagnostic, sensitive and specific in diagnosing P.
      falciparum malaria among pregnant women in this setting. Further studies are
      needed to determine effectiveness in diagnosing other Plasmodium species and to
      compare it with other diagnostic tools e.g. rapid diagnostic tests and PCR.

PMID- 21943213
TI  - Aquaporin-3 positively regulates matrix metalloproteinases via PI3K/AKT signal
      pathway in human gastric carcinoma SGC7901 cells.
AB  - BACKGROUND: matrix metalloproteinases (MMPs) are produced by tumor cells, so they
      may be associated with tumor progression including invasion, migration,
      angiogenesis and metastasis. Aquaporin-3 (AQP3) also plays a critical role in
      gastric cancer cell migration and proliferation. METHODS: In this study, AQP3 was
      silenced or over-expressed in SGC7901 cells. RESULTS: We found a significant
      decrease in MT1-MMP, MMP-2, and MMP-9 expression after AQP3 knockdown, and a
      significant increase in MT1-MMP, MMP-2, and MMP-9 expression after AQP3 over
      expression in SGC7901 cells. We also found that AQP3 silence led to a significant
      decrease of phosphorylation of ser473 in AKT in SGC7901 cells. CONCLUSION: Our
      findings showed that AQP3 might positively regulate MMPs proteins expression
      through PI3K/AKT signal pathway in human gastric carcinoma SGC7901 cells.

PMID- 21943214
TI  - Childhood adversity, mental ill-health and aggressive behavior in an African
      orphanage: Changes in response to trauma-focused therapy and the implementation
      of a new instructional system.
AB  - BACKGROUND: The number of orphans in Sub-Saharan Africa is constantly rising.
      While it is known that family or community care is preferable over institutional
      care of African orphans, little is known about the quality of care in orphanages
      and possibilities of improvement. STUDY 1: METHODS: Exposure to traumatic stress,
      experiences of violence in the home, school and orphanage, as well as mental ill
      health and aggression of 38 children (mean age of M = 8.64 years) living in an
      orphanage in rural Tanzania were assessed at two time points. The severity of
      post-traumatic stress disorder symptoms (PTSD), depressive symptoms, and
      internalizing and externalizing problems were used as indicators of mental ill
      health. RESULTS: Violence experienced in the orphanage correlated more strongly
      with all indicators of mental ill-health than violence in the former home, school
      or neighborhood at time point 1. Additionally, violence experienced in the
      orphanage had a positive relationship with the aggressive behavior of the
      children at time point 2. STUDY 2: METHODS: With the help of the pre-post
      assessment of Study 1, the implementation of a new instructional system and
      psychotherapeutic treatment (KIDNET) for trauma-related illness were evaluated.
      RESULTS: In response to both, a change in the instructional system and
      psychotherapeutic treatment of PTSD, a massive decline in experienced violence
      and in the severity of PTSD-symptoms was found, whereas depressive symptoms and
      internalizing and externalizing problems exhibited little change. CONCLUSIONS:
      These studies show that violence, especially in the orphanage, can severely
      contribute to mental ill-health in orphans and that mental health can be improved
      by implementing a new instructional system and psychotherapeutic treatment in an
      orphanage. Moreover, the results indicate that the experience of violence in an
      orphanage also plays a crucial role in aggressive behavior of the orphans.

PMID- 21943215
TI  - Defining response and remission in psychotherapy research: a comparison of the
      RCI and the method of percent improvement.
AB  - There is no consensus as to how to define response and remission for mental
      disorder treatments. The Reliable Change Index (RCI) is most commonly used in
      psychotherapy research, whereas psychopharmacologists prefer to calculate
      percentage of improvement (PI). We compared both methods using the Beck
      Depression Inventory in 395 depressive outpatients. The overall pre-post effect
      size was d=1.18. The PI-50 (>= 50% improvement from baseline) resulted in outcome
      estimates higher than the RCI: 66.3% vs. 59.2% for response and 50.6% vs. 45.8%
      for remission. We demonstrate that the PI approach is independent of arbitrarily
      chosen reliabilities and reference populations. Furthermore, it takes differences
      of pre-treatment severity into account. It is considered as a valuable extension
      of the established RCI in psychotherapy research.

PMID- 21943216
TI  - Widespread horizontal gene transfer from circular single-stranded DNA viruses to
      eukaryotic genomes.
AB  - BACKGROUND: In addition to vertical transmission, organisms can also acquire
      genes from other distantly related species or from their extra-chromosomal
      elements (plasmids and viruses) via horizontal gene transfer (HGT). It has been
      suggested that phages represent substantial forces in prokaryotic evolution. In
      eukaryotes, retroviruses, which can integrate into host genome as an obligate
      step in their replication strategy, comprise approximately 8% of the human
      genome. Unlike retroviruses, few members of other virus families are known to
      transfer genes to host genomes. RESULTS: Here we performed a systematic search
      for sequences related to circular single-stranded DNA (ssDNA) viruses in publicly
      available eukaryotic genome databases followed by comprehensive phylogenetic
      analysis. We conclude that the replication initiation protein (Rep)-related
      sequences of geminiviruses, nanoviruses and circoviruses have been frequently
      transferred to a broad range of eukaryotic species, including plants, fungi,
      animals and protists. Some of the transferred viral genes were conserved and
      expressed, suggesting that these genes have been coopted to assume cellular
      functions in the host genomes. We also identified geminivirus-like and parvovirus
      like transposable elements in genomes of fungi and lower animals, respectively,
      and thereby provide direct evidence that eukaryotic transposons could derive from
      ssDNA viruses. CONCLUSIONS: Our discovery extends the host range of circular
      ssDNA viruses and sheds light on the origin and evolution of these viruses. It
      also suggests that ssDNA viruses act as an unforeseen source of genetic
      innovation in their hosts.

PMID- 21943217
TI  - Increased atherosclerosis in mice deficient in perilipin1.
AB  - BACKGROUND: Perilipin1, a lipid droplet associated protein has an important role
      in the regulation of lipolysis and lipid storage in adipocytes. Perilipin1 is
      also expressed in foam cells of atheroma plaques and could therefore play a role
      in the accumulation of lipids in arterial wall and in the development of
      atherosclerosis. The aim of the study was to investigate this possible role of
      perilipin1 in atherogenesis. METHODS: Mice deficient in perilipin1 (Plin1-/-)
      were crossed with Ldlr-/- mice. Ldlr-/- and Plin1-/- Ldlr-/- mice received an
      atherogenic diet during 10 or 20 weeks. Blood pressure and plasma lipids
      concentrations were measured. Aortas were collected at the end of the atherogenic
      diet periods for quantification of atheroma lesions (en face method),
      histological and immunohistological studies RESULTS: Ldlr-/- and Plin1-/- Ldlr-/-
      mice had comparable blood pressure and plasma lipids levels. Plin1-/- Ldlr-/-
      mice had a lower body weight and decreased adiposity. The atherosclerotic lesion
      area in Plin1-/-Ldlr-/- mice was moderately increased after 10 weeks of
      atherogenic diet (ns) and significantly higher after 20 weeks (p < 0.01).
      Histology of atheroma plaques was comparable with no sign of increased
      inflammation in Plin1-/- Ldlr-/- mice. CONCLUSION: Perilipin1 ablation in mice
      results in increased atherosclerosis independently of modifications of risk
      factors such as raised blood pressure or plasma lipids levels. These data
      strongly support an atheroprotective role for perilipin1.

PMID- 21943218
TI  - A randomized controlled trial of isotonic versus hypotonic maintenance
      intravenous fluids in hospitalized children.
AB  - BACKGROUND: Isotonic saline has been proposed as a safer alternative to
      traditional hypotonic solutions for intravenous (IV) maintenance fluids to
      prevent hyponatremia. However, the optimal tonicity of maintenance intravenous
      fluids in hospitalized children has not been determined. The objective of this
      study was to estimate and compare the rates of change in serum sodium ([Na]) for
      patients administered either hypotonic or isotonic IV fluids for maintenance
      needs. METHODS: This was a masked controlled trial. Randomization was stratified
      by admission type: medical patients and post-operative surgical patients, aged 3
      months to 18 years, who required IV fluids for at least 8 hours. Patients were
      randomized to receive either 0.45% or 0.9% saline in 5.0% dextrose. Treating
      physicians used the study fluid for maintenance; infusion rate and the use of
      additional fluids were left to their discretion. RESULTS: Sixteen children were
      randomized to 0.9% saline and 21 to 0.45% saline. Baseline characteristics,
      duration (average of 12 hours) and rate of study fluid infusion, and the volume
      of additional isotonic fluids given were similar for the two groups. [Na]
      increased significantly in the 0.9% group (+0.20 mmol/L/h [IQR +0.03, +0.4]; P =
      0.02) and increased, but not significantly, in the 0.45% group (+0.08 mmol/L/h
      [IQR -0.15, +0.16]; P = 0.07). The rate of change and absolute change in serum
      [Na] did not differ significantly between groups. CONCLUSIONS: When administered
      at the appropriate maintenance rate and accompanied by adequate volume expansion
      with isotonic fluids, 0.45% saline did not result in a drop in serum sodium
      during the first 12 hours of fluid therapy in children without severe baseline
      hyponatremia. Confirmation in a larger study is strongly recommended. CLINICAL
      TRIAL REGISTRATION NUMBER: NCT00457873 (http://www.clinicaltrials.gov/).

PMID- 21943219
TI  - Exploring the perspectives of allied health practitioners toward the use of
      journal clubs as a medium for promoting evidence-based practice: a qualitative
      study.
AB  - BACKGROUND: Research evidence suggests that journal clubs (JCs) are one approach
      which can be used to bridge the gap between research and clinical practice.
      However, there are issues which potentially threaten their viability such as on
      going participation or compliance with attendance, which require further
      exploration. The objectives of this study are: to explore the views and
      perspectives of allied health practitioners (AHPs) regarding the use of any type
      of JC in promoting evidence-based practice (EBP); to identify ways in which an
      innovative model of JC developed by the International Centre for Allied Health
      Evidence (iCAHE) might be refined. METHODS: A qualitative descriptive study
      utilising focus group interviews with various groups of AHP was undertaken--
      those who have been exposed to the iCAHE JC model and those who have no
      experience of the iCAHE model (although they may have had exposure to other forms
      of JC). Maximum variation sampling was used to recruit participants for the
      study. Transcripts of focus groups were coded and distilled into content-related
      categories. RESULTS: Six focus groups with 39 AHPs were facilitated. Allied
      health practitioners perspectives' on JCs were classified in five broad
      categories: utility and benefits of a JC, elements of an effective and
      sustainable JC, barriers to participation, incentives for participation, and
      opportunities for improvement in the current iCAHE JC model. Overall, JCs were
      seen as a forum for reflective practice and keeping up-to-date with research
      evidence, and a venue for learning the processes involved in critical appraisal.
      Limited knowledge of statistics and heavy clinical workload were reported as
      barriers to participation in a JC. Strategies such as mentoring, strong support
      from managers, and providing CPD (continuing professional development) points can
      potentially address these barriers. Opportunities for refinement of the current
      iCAHE model were raised. CONCLUSIONS: This study suggests that a structured model
      of JC such as iCAHE's model is acceptable, and likely to be used with enthusiasm
      by AHP to achieve EBP. Future research should explore the impact of iCAHE JC
      compared with no JC exposure, and other forms of exposure to JCs, in influencing
      change in allied health practitioners behaviours and evidence implementation.

PMID- 21943220
TI  - c-Jun NH2-terminal kinase activation is essential for up-regulation of LC3 during
      ceramide-induced autophagy in human nasopharyngeal carcinoma cells.
AB  - BACKGROUND: Autophagy is a dynamic catabolic process characterized by the
      formation of double membrane vacuoles termed autophagosomes. LC3, a homologue of
      yeast Atg8, takes part in autophagosome formation, but the exact regulation
      mechanism of LC3 still needs to be elucidated. METHODS: Ceramide-induced
      autophagy was determined by detecting LC3 expression with Western blotting and
      confocal microscopy in human nasopharyngeal carcinoma cell lines CNE2 and SUNE1.
      The activation of JNK pathway was assessed by Western blotting for phospho
      specific forms of JNK and c-Jun. The JNK activity specific inhibitor, SP600125,
      and siRNA directed against JNK were used to block JNK/c-Jun pathway. ChIP and
      luciferase reporter analysis were applied to determine whether c-Jun was involved
      in the regulation of LC3 transcription. RESULTS: Ceramide-treated cells exhibited
      the characteristics of autophagy and JNK pathway activation. Inhibition of JNK
      pathway could block the ceramide-induced autophagy and the up-regulation of LC3
      expression. Transcription factor c-Jun was involved in LC3 transcription
      regulation in response to ceramide treatment. CONCLUSIONS: Ceramide could induce
      autophagy in human nasopharyngeal carcinoma cells, and activation of JNK pathway
      was involved in ceramide-induced autophagy and LC3 expression.

PMID- 21943221
TI  - Evaluation of an electronic warfarin nomogram for anticoagulation of hemodialysis
      patients.
AB  - BACKGROUND: Warfarin nomograms to guide dosing have been shown to improve control
      of the international normalized ratio (INR) in the general outpatient setting.
      However, the effectiveness of these nomograms in hemodialysis patients is
      unknown. We evaluated the effectiveness of anticoagulation using an electronic
      warfarin nomogram administered by nurses in outpatient hemodialysis patients,
      compared to physician directed therapy. METHODS: Hemodialysis patients at any of
      the six outpatient clinics in Calgary, Alberta, treated with warfarin
      anticoagulation were included. Two five-month time periods were compared: prior
      to and post implementation of the nomogram. The primary endpoint was adequacy of
      anticoagulation (proportion of INR measurements within range +/- 0.5 units).
      RESULTS: Overall, 67 patients were included in the pre- and 55 in the post-period
      (with 40 patients in both periods). Using generalized linear mixed models, the
      adequacy of INR control was similar in both periods for all range INR levels: in
      detail, range INR 1.5 to 2.5 (pre 93.6% (95% CI: 88.6% - 96.5%); post 95.6% (95%
      CI: 89.4% - 98.3%); p = 0.95); INR 2.0 to 3.0 (pre 82.2% (95% CI: 77.9% - 85.8%);
      post 77.4% (95% CI: 72.0% - 82.0%); p = 0.20); and, INR 2.5 to 3.5 (pre 84.3%
      (95% CI: 59.4% - 95.1%); post 66.8% (95% CI: 39.9% - 86.0%); p = 0.29). The mean
      number of INR measurements per patient decreased significantly between the pre-
      (30.5, 95% CI: 27.0 - 34.0) and post- (22.3, 95% CI: 18.4 - 26.1) (p = 0.003)
      period. There were 3 bleeding events in each of the periods. CONCLUSIONS: An
      electronic warfarin anticoagulation nomogram administered by nurses achieved INR
      control similar to that of physician directed therapy among hemodialysis patients
      in an outpatient setting, with a significant reduction in frequency of testing.
      Future controlled trials are required to confirm the efficacy of this nomogram.

PMID- 21943222
TI  - Emergence of Japanese encephalitis virus genotype V in the Republic of Korea.
AB  - BACKGROUND: Japanese encephalitis virus (JEV) genotype V reemerged in Asia
      (China) in 2009 after a 57-year hiatus from the continent, thereby emphasizing a
      need to increase regional surveillance efforts. Genotypic characterization was
      performed on 19 JEV-positive mosquito pools (18 pools of Culex tritaeniorhynchus
      and 1 pool of Cx. bitaeniorhynchus) from a total of 64 positive pools collected
      from geographically different locations throughout the Republic of Korea (ROK)
      during 2008 and 2010. FINDINGS: Two regions of the JEV genome were sequenced from
      19 pools; the envelope gene and the nonstructural protein 5 (NS5)/3'-untranslated
      region (UTR). Eighteen pools of Culex tritaeniorhynchus and one pool of Cx.
      bitaeniorhynchus were positive for genotype I and genotype V, respectively.
      Sequence alignment of the complete E gene from Cx. bitaeniorhynchus showed high
      amino acid similarity (98.8%) to the Muar strain, characterized as the first
      report of genotype V, isolated from an encephalitis patient in Malaysia in 1952.
      CONCLUSION: This study represents the first report of JEV genotype V in the ROK.
      The reemergence of genotype V in Asia (China and ROK) after more than a half
      century and its discovery in Cx. bitaeniorhynchus, a mosquito species previously
      unknown to carry JEV in the ROK, emphasizes the need for enhanced JE surveillance
      to monitor the dynamics of JEV strains within the region. Future findings may
      have implications with regard to JEV vaccination/prevention strategies.

PMID- 21943223
TI  - Altered expression of miR-21, miR-125b, and miR-203 indicates a role for these
      microRNAs in oral lichen planus.
AB  - BACKGROUND: Oral lichen planus (OLP), which is a chronic inflammatory disease of
      the oral mucosa with unknown etiology, affects about 2% of the population.
      MicroRNAs are small non-coding RNAs involved in normal processes such as
      development and differentiation as well as progression of human diseases. The aim
      of this study was to investigate the expression of miR-21, miR-125b, and miR-203
      and to compare RNA levels of their potential targets, the tumor suppressor p53
      and its relative p63, both known to be deregulated in OLP. METHODS: In biopsies
      from 20 patients with OLP and 20 age- and sex-matched healthy controls,
      epithelium was laser dissected and analyzed for the expression of miR-21, miR
      125b, miR-203, p53, and p63 using qRT/PCR. RESULTS: Increased expression of miR
      21 and miR-203, decreased expression of miR-125, and down-regulation of p53 and
      DeltaNp63 RNA were seen in OLP compared to normal oral mucosa. When comparing
      microRNA expression to levels of p53 and p63 RNA, a significant negative
      correlation was seen between DeltaNp63 and miR-203 and between miR-21 and p53,
      respectively. CONCLUSION: Results indicate a role for the studied microRNAs in
      changes seen in OLP.

PMID- 21943224
TI  - Adherence to prescribed artemisinin-based combination therapy in Garissa and
      Bunyala districts, Kenya.
AB  - BACKGROUND: Following the development of resistance to anti-malarial mono
      therapies, malaria endemic countries in Africa now use artemisinin-based
      combination therapy (ACT) as recommended first-line treatment for uncomplicated
      malaria. Patients' adherence to ACT is an important factor to ensure treatment
      efficacy, as well as to reduce the likelihood of parasite resistance to these
      drugs. This study reports adherence to a specific ACT, artemether-lumefantrine
      (AL), under conditions of routine clinical practice in Kenya. METHOD: The study
      was undertaken in Garissa and Bunyala districts among outpatients of five
      government health facilities. Patients treated with AL were visited at home four
      days after having been prescribed the drug. Respondents (patients >= 15 years and
      caregivers of patients < 15 years) were interviewed using a standardized
      questionnaire, AL blister packs were physically inspected and the adherence
      status of patients was then recorded. Multivariate logistic regression modelling
      was used to determine predictors of adherence. RESULTS: Of the 918 patients
      included in the study, 588 (64.1%) were 'probably adherent', 291 (31.7%) were
      'definitely non-adherent' and 39 (4.2%) were 'probably non-adherent'. Six factors
      were found to be significant predictors of adherence: patient knowledge of the
      ACT dosing regimen (odds ratio (OR) = 1.76; 95% CI = 1.32-2.35), patient age (OR
      = 1.65; 95% CI = 1.02-1.85), respondent age (OR = 1.37; 95% CI = 1.10-2.48),
      whether a respondent had seen AL before (OR = 1.46; 95% CI = 1.08-1.98), whether
      a patient had reported dislikes to AL (OR = 0.62 95% CI = 0.47-0.82) and whether
      a respondent had waited more than 24 hours to seek treatment (OR = 0.73; 95% CI =
      0.54-0.99). CONCLUSION: Overall, adherence to AL was found to be low in both
      Garissa and Bunyala districts, with patient knowledge of the AL dosing regimen
      found to be the strongest predictor of adherence. Interventions aimed at
      increasing community awareness of the AL dosing regimen, use of child friendly
      formulations and improving health workers' prescribing practices are likely to
      ensure higher adherence to AL and eventual treatment success.

PMID- 21943225
TI  - Chotosan (Diaoteng San)-induced improvement of cognitive deficits in senescence
      accelerated mouse (SAMP8) involves the amelioration of angiogenic/neurotrophic
      factors and neuroplasticity systems in the brain.
AB  - BACKGROUND: Chotosan (CTS, Diaoteng San), a Kampo medicine (ie Chinese medicine)
      formula, is reportedly effective in the treatment of patients with cerebral
      ischemic insults. This study aims to evaluate the therapeutic potential of CTS in
      cognitive deficits and investigates the effects and molecular mechanism(s) of CTS
      on learning and memory deficits and emotional abnormality in an animal aging
      model, namely 20-week-old senescence-accelerated prone mice (SAMP8), with and
      without a transient ischemic insult (T2VO). METHODS: Age-matched senescence
      resistant inbred strain mice (SAMR1) were used as control. SAMP8 received T2VO
      (T2VO-SAMP8) or sham operation (sham-SAMP8) at day 0. These SAMP8 groups were
      administered CTS (750 mg/kg, p.o.) or water daily for three weeks from day 3.
      RESULTS: Compared with the control group, both sham-SAMP8 and T2VO-SAMP8 groups
      exhibited cognitive deficits in the object discrimination and water maze tests
      and emotional abnormality in the elevated plus maze test. T2VO significantly
      exacerbated spatial cognitive deficits of SAMP8 elucidated by the water maze
      test. CTS administration ameliorated the cognitive deficits and emotional
      abnormality of sham- and T2VO-SAMP8 groups. Western blotting and
      immunohistochemical studies revealed a marked decrease in the levels of
      phosphorylated forms of neuroplasticity-related proteins, N-methyl-D-aspartate
      receptor 1 (NMDAR1), Ca2+/calmodulin-dependent protein kinase II (CaMKII), cyclic
      AMP responsive element binding protein (CREB) and brain-derived neurotrophic
      factor (BDNF) in the frontal cortices of sham-SAMP8 and T2VO-SAMP8. Moreover,
      these animal groups showed significantly reduced levels of
      vasculogenesis/angiogenesis factors, vascular endothelial growth factor (VEGF),
      VEGF receptor type 2 (VEGFR2), platelet-derived growth factor-A (PDGF-A) and PDGF
      receptor alpha (PDGFRalpha). CTS treatment reversed the expression levels of
      these factors down-regulated in the brains of sham- and T2VO-SAMP8. CONCLUSION:
      Recovery of impaired neuroplasticity system and VEGF/PDGF systems may play a role
      in the ameliorative effects of CTS on cognitive dysfunction caused by aging and
      ischemic insult.

PMID- 21943226
TI  - Multiple recent horizontal transfers of the cox1 intron in Solanaceae and
      extended co-conversion of flanking exons.
AB  - BACKGROUND: The most frequent case of horizontal transfer in plants involves a
      group I intron in the mitochondrial gene cox1, which has been acquired via some
      80 separate plant-to-plant transfer events among 833 diverse angiosperms
      examined. This homing intron encodes an endonuclease thought to promote the
      intron's promiscuous behavior. A promising experimental approach to study
      endonuclease activity and intron transmission involves somatic cell
      hybridization, which in plants leads to mitochondrial fusion and genome
      recombination. However, the cox1 intron has not yet been found in the ideal group
      for plant somatic genetics - the Solanaceae. We therefore undertook an extensive
      survey of this family to find members with the intron and to learn more about the
      evolutionary history of this exceptionally mobile genetic element. RESULTS:
      Although 409 of the 426 species of Solanaceae examined lack the cox1 intron, it
      is uniformly present in three phylogenetically disjunct clades. Despite strong
      overall incongruence of cox1 intron phylogeny with angiosperm phylogeny, two of
      these clades possess nearly identical intron sequences and are monophyletic in
      intron phylogeny. These two clades, and possibly the third also, contain a co
      conversion tract (CCT) downstream of the intron that is extended relative to all
      previously recognized CCTs in angiosperm cox1. Re-examination of all published
      cox1 genes uncovered additional cases of extended co-conversion and identified a
      rare case of putative intron loss, accompanied by full retention of the CCT.
      CONCLUSIONS: We infer that the cox1 intron was separately and recently acquired
      by at least three different lineages of Solanaceae. The striking identity of the
      intron and CCT from two of these lineages suggests that one of these three intron
      captures may have occurred by a within-family transfer event. This is consistent
      with previous evidence that horizontal transfer in plants is biased towards
      phylogenetically local events. The discovery of extended co-conversion suggests
      that other cox1 conversions may be longer than realized but obscured by the
      exceptional conservation of plant mitochondrial sequences. Our findings provide
      further support for the rampant-transfer model of cox1 intron evolution and
      recommend the Solanaceae as a model system for the experimental analysis of cox1
      intron transfer in plants.

PMID- 21943228
TI  - Maspin and MCM2 immunoprofiling in salivary gland carcinomas.
AB  - BACKGROUND: The pathogenesis of salivary gland carcinomas is very complex and
      prognostic markers are difficult to find in these carcinomas of which the
      different subtypes have varying malignant potential. The study was conducted to
      examine the cellular distribution of maspin and MCM2 in salivary gland carcinomas
      and their value to predict lymph node metastasis. MATERIALS AND METHODS: Fifty
      three paraffin blocks of different lesions (15 muco-epidermoid carcinoma, 14
      adenoid cystic carcinoma, 3 epi-myoepithelial carcinoma, 5 salivary duct
      carcinoma, 5 malignant pleomorphic adenoma, 6 polymorphous low grade
      adenocarcinoma and 5 acinic cell carcinoma) were prepared for immunohistochemical
      staining with maspin and MCM2 antibodies. ANOVA and Pearson correlation tests
      were used for the statistical analysis of the results. RESULTS: All salivary
      gland carcinomas express maspin and MCM2 with variable cellular localization.
      There was a significant difference in the expression of each antibody between
      mucoepidermoid carcinoma, adenoid cystic carcinoma and polymorphous low grade
      adenocarcinoma. No association was found between examined markers and lymph node
      metastasis. CONCLUSIONS: Salivary gland carcinomas express maspin and MCM2 with
      variable levels and cellular localization, consisting important markers of
      biological behavior in these tumors. The level of MCM2 expression can be used in
      the differential diagnosis of adenoid cystic carcinoma and polymorphous low grade
      adenocarcinoma. Further study with large sample size is recommended to assess
      their value in prediction of lymph node metastasis.

PMID- 21943229
TI  - Geophysical monitoring and reactive transport modeling of ureolytically-driven
      calcium carbonate precipitation.
AB  - Ureolytically-driven calcium carbonate precipitation is the basis for a
      promising in-situ remediation method for sequestration of divalent radionuclide
      and trace metal ions. It has also been proposed for use in geotechnical
      engineering for soil strengthening applications. Monitoring the occurrence,
      spatial distribution, and temporal evolution of calcium carbonate precipitation
      in the subsurface is critical for evaluating the performance of this technology
      and for developing the predictive models needed for engineering application. In
      this study, we conducted laboratory column experiments using natural sediment and
      groundwater to evaluate the utility of geophysical (complex resistivity and
      seismic) sensing methods, dynamic synchrotron x-ray computed tomography (micro
      CT), and reactive transport modeling for tracking ureolytically-driven calcium
      carbonate precipitation processes under site relevant conditions. Reactive
      transport modeling with TOUGHREACT successfully simulated the changes of the
      major chemical components during urea hydrolysis. Even at the relatively low
      level of urea hydrolysis observed in the experiments, the simulations predicted
      an enhanced calcium carbonate precipitation rate that was 3-4 times greater than
      the baseline level. Reactive transport modeling results, geophysical monitoring
      data and micro-CT imaging correlated well with reaction processes validated by
      geochemical data. In particular, increases in ionic strength of the pore fluid
      during urea hydrolysis predicted by geochemical modeling were successfully
      captured by electrical conductivity measurements and confirmed by geochemical
      data. The low level of urea hydrolysis and calcium carbonate precipitation
      suggested by the model and geochemical data was corroborated by minor changes in
      seismic P-wave velocity measurements and micro-CT imaging; the latter provided
      direct evidence of sparsely distributed calcium carbonate precipitation. Ion
      exchange processes promoted through NH4+ production during urea hydrolysis were
      incorporated in the model and captured critical changes in the major metal
      species. The electrical phase increases were potentially due to ion exchange
      processes that modified charge structure at mineral/water interfaces. Our study
      revealed the potential of geophysical monitoring for geochemical changes during
      urea hydrolysis and the advantages of combining multiple approaches to understand
      complex biogeochemical processes in the subsurface.

PMID- 21943230
TI  - Entrainment of marginally stable excitation waves by spatially extended sub
      threshold periodic forcing.
AB  - We introduce a novel approach of stabilizing the dynamics of excitation waves by
      spatially extended sub-threshold periodic forcing. Entrainment of unstable
      primary waves has been studied numerically for different amplitudes and
      frequencies of additional sub-threshold stimuli. We determined entrainment
      regimes under which excitation blocks were transformed into consistent 1:1
      responses. These responses were spatially homogeneous and synchronized in the
      entire excitable medium. Compared to primary pulses, pulses entrained by
      secondary stimulations were stable at considerably shorter periods which
      decreased at higher amplitudes and greater number of secondary stimuli. Our
      results suggest a practical methodology for stabilization of excitation in
      reaction-diffusion media such as nerve tissue with regions of reduced
      excitability.

PMID- 21943231
TI  - Green chemistry, polymers of low concern, and animal testing and welfare.

PMID- 21943227
TI  - Transcriptional analysis of cell growth and morphogenesis in the unicellular
      green alga Micrasterias (Streptophyta), with emphasis on the role of expansin.
AB  - BACKGROUND: Streptophyte green algae share several characteristics of cell growth
      and cell wall formation with their relatives, the embryophytic land plants. The
      multilobed cell wall of Micrasterias denticulata that rebuilds symmetrically
      after cell division and consists of pectin and cellulose, makes this unicellular
      streptophyte alga an interesting model system to study the molecular controls on
      cell shape and cell wall formation in green plants. RESULTS: Genome-wide
      transcript expression profiling of synchronously growing cells identified 107
      genes of which the expression correlated with the growth phase. Four transcripts
      showed high similarity to expansins that had not been examined previously in
      green algae. Phylogenetic analysis suggests that these genes are most closely
      related to the plant EXPANSIN A family, although their domain organization is
      very divergent. A GFP-tagged version of the expansin-resembling protein MdEXP2
      localized to the cell wall and in Golgi-derived vesicles. Overexpression
      phenotypes ranged from lobe elongation to loss of growth polarity and planarity.
      These results indicate that MdEXP2 can alter the cell wall structure and, thus,
      might have a function related to that of land plant expansins during cell
      morphogenesis. CONCLUSIONS: Our study demonstrates the potential of M.
      denticulata as a unicellular model system, in which cell growth mechanisms have
      been discovered similar to those in land plants. Additionally, evidence is
      provided that the evolutionary origins of many cell wall components and
      regulatory genes in embryophytes precede the colonization of land.

PMID- 21943232
TI  - Metrifonate alters antioxidant levels and caspase activity in cerebral cortex of
      Wistar rats.
AB  - Metrifonate (trichlorfon) is an inhibitor of acetylcholinesterase (AChE). It was
      used as an Alzheimer's disease (AD) drug; however, the application was withdrawn
      due to adverse effects. Implication of metrifonate for the antioxidant status and
      regulation of apoptotic processes was evaluated in the present study. Wistar rats
      (six per group) were exposed subcutaneously to either 60 or 120 mg/kg of body
      weight of metrifonate and compared with the controls treated with saline only.
      Cerebral cortex and liver tissues were collected from animals 40 min after
      exposure. Activities of AChE, glutathione reductase, glutathione-S-transferase,
      caspase 3, total protein level, thiobarbituric acid reactive substances, reduced
      glutathione level and ferric reducing antioxidant power (FRAP) were assayed in
      the tissue samples. Metrifonate had only lower impact on oxidative stress in the
      liver. Cerebral cortex tissues had decreased AChE and increased caspase 3
      activities as well as the FRAP level. Owing to the novel findings, suitability of
      metrifonate for AD therapy is discussed.

PMID- 21943233
TI  - Design of a new test chamber for evaluation of the toxicity of rubber infill.
AB  - A test chamber was projected and built (according to ISO 16000-9 Standard) to
      simulate atmospheric conditions experienced by rubber infill (when applied in
      synthetic turf pitches) and measure accurately the airborne emissions of
      pollutants such as dusts and volatile organic compounds (VOC), as well as
      pollutants present in leachates. It should be pointed out that standard ISO 16000
      9 is only concerned with the determination of the emission of VOC from building
      products and furnishing (not specific of synthetic turf materials), whereas other
      standards are concerned with the emission of leachates only. This procedure is to
      be considered as a technical option to the lysimeter "global turf system
      evaluation" when the rubber infill alone is to be evaluated. The advantage of the
      proposed option considering this "test chamber" is its simplicity and economy.
      This test chamber is actually installed and being used for tests in LAIST.

PMID- 21943234
TI  - DEK regulates hematopoietic stem engraftment and progenitor cell proliferation.
AB  - DEK is a biochemically distinct protein that is generally found in the nucleus,
      where it is vital to global heterochromatin integrity. However, DEK is also
      secreted by cells (eg, macrophages) and influences other adjacent cells (eg, acts
      as a chemoattractant for certain mature blood cells). We hypothesized that DEK
      may modulate functions of hematopoietic stem (HSCs) and progenitor (HPCs) cells.
      C57Bl/6 mice were used to demonstrate that absolute numbers and cycling status of
      HPCs (colony forming unit-granulocyte macrophage [CFU-GM], burst forming unit
      erythroid [BFU-E], and colony forming unit-granulocyte erythroid macrophage
      megakaryocyte [CFU-GEMM]) in bone marrow (BM) and spleen were significantly
      enhanced in DEK -/- as compared with wild-type (WT) control mice. Moreover,
      purified recombinant DEK protein inhibited colony formation in vitro by CFU-GM,
      BFU-E, and CFU-GEMM from WT BM cells and human cord blood (CB) cells in a dose
      dependent fashion, demonstrating that DEK plays a negative role in HPC
      proliferation in vitro and in vivo. Suppression was direct acting as determined
      by inhibition of proliferation of single isolated CD34(+) CB cells in vitro. In
      contrast, DEK -/- BM cells significantly demonstrated reduced long term
      competitive and secondary mouse repopulating HSC capacity compared with WT BM
      cells, demonstrating that DEK positively regulates engrafting capability of self
      renewing HSCs. This demonstrates that DEK has potent effects on HSCs, HPCs, and
      hematopoiesis, information of biological and potential clinical interest.

PMID- 21943235
TI  - Elevated levels of circulating IL-7 and IL-15 in patients with early stage
      prostate cancer.
AB  - BACKGROUND: Chronic inflammation has been suggested to favour prostate cancer
      (PCA) development. Interleukins (IL) represent essential inflammation mediators.
      IL-2, IL-7, IL-15 and IL-21, sharing a common receptor gamma chain (c-gamma),
      control T lymphocyte homeostasis and proliferation and play major roles in
      regulating cancer-immune system interactions. We evaluated local IL-2, IL-7, IL
      15 and IL-21 gene expression in prostate tissues from patients with early stage
      PCA or benign prostatic hyperplasia (BPH). As control, we used IL-6 gene,
      encoding an IL involved in PCA progression. IL-6, IL-7 and IL-15 titres were also
      measured in patients' sera. METHODS: Eighty patients with BPH and 79 with early
      (1 to 2c) stage PCA were enrolled. Gene expression in prostate tissues was
      analyzed by quantitative real-time PCR (qRT-PCR). Serum IL concentrations and
      acute phase protein titres were evaluated by ELISA. Mann-Whitney, Wilcoxon and
      chi(2) tests were used to compare IL gene expression and serum titers in the two
      groups of patients. Receiver operating characteristic (ROC) curves were
      constructed to evaluate the possibility to distinguish sera from different groups
      of patients based on IL titers. RESULTS: IL-2 and IL-21 gene expression was
      comparably detectable, with low frequency and at low extents, in PCA and BPH
      tissues. In contrast, IL-6, IL-7 and IL-15 genes were expressed more frequently
      (p < 0.0001, p = 0.0047 and p = 0.0085, respectively) and to significantly higher
      extents (p = 0.0051, p = 0.0310 and p = 0.0205, respectively) in early stage PCA
      than in BPH tissues. Corresponding proteins could be detected to significantly
      higher amounts in sera from patients with localized PCA, than in those from
      patients with BPH (p = 0.0153, p = 0.0174 and p = 0.0064, respectively). Analysis
      of ROC curves indicates that IL-7 (p = 0.0039), but not IL-6 (p = 0.2938) or IL
      15 (p = 0.1804) titres were able to distinguish sera from patients with
      malignancy from those from patients with benign disease. Serum titres of C
      reactive (CRP), high mobility group B1 (HMGB1) and serum amyloid A (SAA) acute
      phase proteins were similar in both groups of patients. CONCLUSIONS: Expression
      IL-7 and IL-15 genes in prostate tissues and corresponding serum titres are
      significantly increased in patients with early stage PCA as compared with
      patients with BPH.

PMID- 21943236
TI  - Apoptosis in cancer: from pathogenesis to treatment.
AB  - Apoptosis is an ordered and orchestrated cellular process that occurs in
      physiological and pathological conditions. It is also one of the most studied
      topics among cell biologists. An understanding of the underlying mechanism of
      apoptosis is important as it plays a pivotal role in the pathogenesis of many
      diseases. In some, the problem is due to too much apoptosis, such as in the case
      of degenerative diseases while in others, too little apoptosis is the culprit.
      Cancer is one of the scenarios where too little apoptosis occurs, resulting in
      malignant cells that will not die. The mechanism of apoptosis is complex and
      involves many pathways. Defects can occur at any point along these pathways,
      leading to malignant transformation of the affected cells, tumour metastasis and
      resistance to anticancer drugs. Despite being the cause of problem, apoptosis
      plays an important role in the treatment of cancer as it is a popular target of
      many treatment strategies. The abundance of literature suggests that targeting
      apoptosis in cancer is feasible. However, many troubling questions arise with the
      use of new drugs or treatment strategies that are designed to enhance apoptosis
      and critical tests must be passed before they can be used safely in human
      subjects.

PMID- 21943237
TI  - A multi-center, qualitative assessment of pediatrician and maternal perspectives
      on rotavirus vaccines and the detection of Porcine circovirus.
AB  - BACKGROUND: In 2010, researchers using novel laboratory techniques found that US
      licensed rotavirus vaccines contain DNA or DNA fragments from Porcine circovirus
      (PCV), a virus common among pigs but not believed to cause illness in humans. We
      sought to understand pediatricians' and mothers' perspectives on this finding.
      METHODS: We conducted three iterations of focus groups for pediatricians and non
      vaccine hesitant mothers in Seattle, WA, Cincinnati, OH, and Rochester, NY. Focus
      groups explored perceptions of rotavirus disease, rotavirus vaccination, and
      attitudes about the detection of PCV material in rotavirus vaccines. RESULTS:
      Pediatricians understood firsthand the success of rotavirus vaccines in
      preventing severe acute gastroenteritis among infants and young children. They
      measured this benefit against the theoretical risk of DNA material from PCV in
      rotavirus vaccines, determining overall that the PCV finding was of no clinical
      significance. Particularly influential was the realization that the large,
      randomized clinical trials that found both vaccines to be highly effective and
      safe were conducted with DNA material from PCV already in the vaccines.Most
      mothers supported the ideal of full disclosure regarding vaccination risks and
      benefits. However, with a scientific topic of this complexity, simplified
      information regarding PCV material in rotavirus vaccines seemed frightening and
      suspicious, and detailed information was frequently overwhelming. Mothers often
      remarked that if they did not understand a medical or technical topic regarding
      their child's health, they relied on their pediatrician's guidance.Many mothers
      and pediatricians were also concerned that persons who abstain from pork
      consumption for religious or personal reasons may have unsubstantiated fears of
      the PCV finding. CONCLUSIONS: Pediatricians considered the detection of DNA
      material from PCV in rotavirus vaccines a "non-issue" and reported little
      hesitation in continuing to recommend the vaccines. Mothers desired transparency,
      but ultimately trusted their pediatrician's recommendation. Both vaccines are
      currently approved for their intended use, and no risk of human PCV illness has
      been reported. Communicating this topic to pediatricians and mothers requires
      sensitivity to a broad range of technical understanding and personal concerns.

PMID- 21943238
TI  - Intravenous leiomyomatosis of the uterus with extension to the right heart.
AB  - A 42-year-old woman admitted with debilitation and engorgement both lower
      extremities. Transthoracic two-dimensional echocardiography, abdominal ultrasound
      and computerized tomography revealed a lobulated pelvic mass, a mass within right
      internal iliac vein, both common iliac vein, as well as the inferior vena cava,
      extending into the right atrium. In addition, echocardiography and abdominal
      ultrasound showed the tumor of right atrium and inferior vena cave has no stalk
      and has well-demarcated borders with the wall of right atrium and inferior vena
      cave. Hence, the presumptive diagnosis of IVL was made by echocardiography and
      abdominal ultrasound and the presumptive diagnosis of sarcoma with invasion in
      right internal iliac vein, both common iliac vein, the inferior vena cava, as
      well as the right atrium was made by multi-detector-row computerized tomography.
      The patient underwent a one-stage combined multidisciplinary thoraco-abdominal
      operation under general anaesthetic. Subsequently the pathologic report confirmed
      IVL.

PMID- 21943239
TI  - An appraisal of students' awareness of "self-reflection" in a first-year
      pathology course of undergraduate medical/dental education.
AB  - BACKGROUND: Self-reflection and reflective practice are increasingly considered
      as essential attributes of competent professionals functioning in complex and
      ever-changing healthcare systems of the 21st century. The aim of this study was
      to determine the extent of students' awareness and understanding of the
      reflective process and the meaning of 'self-reflection' within the contextual
      framework of their learning environment in the first-year of their medical/dental
      education. We endorse that the introduction of such explicit educational tasks at
      this early stage enhances and promotes students' awareness, understanding, and
      proficiency of this skill in their continuing life-long health professional
      learning. METHODS: Over two years, students registered in first-year pathology at
      the University of Saskatchewan were introduced to a self-reflection assignment
      which comprised in the submission of a one-page reflective document to a template
      of reflective questions provided in the given context of their learning
      environment. This was a mandatory but ungraded component at the midterm and final
      examinations. These documents were individually analyzed and thematically
      categorized to a "5 levels-of-reflection-awareness" scale using a specially
      designed rubric based on the accepted major theories of reflection that included
      students' identification of: 1) personal abilities, 2) personal learning styles
      3) relationships between course material and student history 4) emotional
      responses and 5) future applications. RESULTS: 410 self-reflection documents were
      analyzed. The student self-awareness on personal learning style (72.7% level 3+)
      and course content (55.2% level 3+) were well-reflected. Reflections at a level 1
      awareness included identification of a) specific teaching strategies utilized to
      enhance learning (58.4%), b) personal strengths/weaknesses (53%), and c)
      emotional responses, values, and beliefs (71.5%). Students' abilities to connect
      information to life experiences and to future events with understanding were more
      evenly distributed across all 5 levels of reflection-awareness. CONCLUSIONS:
      Exposure to self-reflection assignments in the early years of undergraduate
      medical education increases student awareness and promotes the creation of
      personal meaning of one's reactions, values, and premises in the context of
      student learning environments. Early introduction with repetition to such
      cognitive processes as practice tools increases engagement in reflection that may
      facilitate proficiency in mastering this competency leading to the creation of
      future reflective health professionals.

PMID- 21943241
TI  - Patient and provider determinants of nephrology referral in older adults with
      severe chronic kidney disease: a survey of provider decision making.
AB  - BACKGROUND: Although chronic kidney disease (CKD) disproportionately affects
      older adults, they are less likely to be referred to a nephrologist. Factors that
      influence the referral decisions of primary care providers (PCPs) specifically
      for older CKD patients have been incompletely described. Patient factors such as
      dementia, functional disability, and co-morbidity may complicate the decision to
      refer an older adult. This study evaluated the role of patient and PCP factors in
      the referral decisions for older adults with stage 4 CKD. METHODS: We
      administered a two-part survey to study the decisions of practicing PCPs. First,
      using a blocked factorial design, vignettes systematically varied 6 patient
      characteristics: age, race, gender, co-morbidity, functional status, and
      cognitive status. CKD severity, patient preferences, and degree of anemia were
      held constant. Second, covariates from a standard questionnaire included PCP
      estimates of life expectancy, demographics, reaction to clinical uncertainty, and
      risk aversion. The main outcome was the decision to refer to the nephrologist.
      Random effects logistic regression models tested independent associations of
      predictor variables with the referral decision. RESULTS: More than half (62.5%)
      of all PCP decisions (n = 680) were to refer to a nephrologist. Vignette-based
      factors that independently decreased referral included older patient age (OR =
      0.27; 95% CI, 0.15 to 0.48) and having moderate dementia (OR = 0.14; 95%CI, 0.07
      to 0.25). There were no associations between co-morbidity or impaired functional
      activity with the referral decision. Survey-based PCP factors that significantly
      increased the referral likelihood include female gender (OR = 7.75; 95%CI, 2.07
      to 28.93), non-white race (OR = 30.29; 95%CI, 1.30 to 703.73), those who expect
      nephrologists to discuss goals of care (OR = 53.13; 95%CI, 2.42 to 1168.00),
      those with higher levels of anxiety about uncertainty (OR = 1.28; 95%CI, 1.04 to
      1.57), and those with greater risk aversion (OR = 3.39; 95%CI, 1.02 to 11.24).
      CONCLUSIONS: In this decision making study using hypothetical clinical vignettes,
      we found that the PCP decision to refer older patients with severe CKD to a
      nephrologist reflects a complex interplay between patient and provider factors.
      Age, dementia, and several provider characteristics weighed more heavily than co
      morbidity and functional status in PCP referral decisions. These results suggest
      that practice guidelines should develop a more nuanced approach to the referral
      of older adults with CKD.

PMID- 21943240
TI  - Hyperhomocysteinemia is independently associated with albuminuria in the
      population-based CoLaus study.
AB  - BACKGROUND: Increased serum levels of homocysteine and uric acid have each been
      associated with cardiovascular risk. We analyzed whether homocysteine and uric
      acid were associated with glomerular filtration rate (GFR) and albuminuria
      independently of each other. We also investigated the association of MTHFR
      polymorphisms related to homocysteine with albuminuria to get further insight
      into causality. METHODS: This was a cross-sectional population-based study in
      Caucasians (n = 5913). Hyperhomocysteinemia was defined as total serum
      homocysteine >= 15 MUmol/L. Albuminuria was defined as urinary albumin-to
      creatinine ratio > 30 mg/g. RESULTS: Uric acid was associated positively with
      homocysteine (r = 0.246 in men and r = 0.287 in women, P < 0.001). The prevalence
      of albuminuria increased across increasing homocysteine categories (from 6.4% to
      17.3% in subjects with normal GFR and from 3.5% to 14.5% in those with reduced
      GFR, P for trend < 0.005). Hyperhomocysteinemia (OR = 2.22, 95% confidence
      interval: 1.60-3.08, P < 0.001) and elevated serum uric acid (OR = 1.27, 1.08
      1.50, per 100 MUmol/L, P = 0.004) were significantly associated with albuminuria,
      independently of hypertension and type 2 diabetes. The 2-fold higher risk of
      albuminuria associated with hyperhomocysteinemia was similar to the risk
      associated with hypertension or diabetes. MTHFR alleles related to higher
      homocysteine were associated with increased risk of albuminuria. CONCLUSIONS: In
      the general adult population, elevated serum homocysteine and uric acid were
      associated with albuminuria independently of each other and of renal function.

PMID- 21943243
TI  - Biomass expansion factor and root-to-shoot ratio for Pinus in Brazil.
AB  - The Biomass Expansion Factor (BEF) and the Root-to-Shoot Ratio (R) are variables
      used to quantify carbon stock in forests. They are often considered as constant
      or species/area specific values in most studies. This study aimed at showing tree
      size and age dependence upon BEF and R and proposed equations to improve forest
      biomass and carbon stock. Data from 70 sample Pinus spp. grown in southern Brazil
      trees in different diameter classes and ages were used to demonstrate the
      correlation between BEF and R, and forest inventory data, such as DBH, tree
      height and age. Total dry biomass, carbon stock and CO2 equivalent were simulated
      using the IPCC default values of BEF and R, corresponding average calculated from
      data used in this study, as well as the values estimated by regression equations.
      The mean values of BEF and R calculated in this study were 1.47 and 0.17,
      respectively. The relationship between BEF and R and the tree measurement
      variables were inversely related with negative exponential behavior. Simulations
      indicated that use of fixed values of BEF and R, either IPCC default or current
      average data, may lead to unreliable estimates of carbon stock inventories and
      CDM projects. It was concluded that accounting for the variations in BEF and R
      and using regression equations to relate them to DBH, tree height and age, is
      fundamental in obtaining reliable estimates of forest tree biomass, carbon sink
      and CO2 equivalent.

PMID- 21943242
TI  - A new high-throughput method for simultaneous detection of drug resistance
      associated mutations in Plasmodium vivax dhfr, dhps and mdr1 genes.
AB  - BACKGROUND: Reports of severe cases and increasing levels of drug resistance
      highlight the importance of improved Plasmodium vivax case management. Whereas
      monitoring P. vivax resistance to anti-malarial drug by in vivo and in vitro
      tests remain challenging, molecular markers of resistance represent a valuable
      tool for high-scale analysis and surveillance studies. A new high-throughput
      assay for detecting the most relevant markers related to P. vivax drug resistance
      was developed and assessed on Papua New Guinea (PNG) patient isolates. METHODS:
      Pvdhfr, pvdhps and pvmdr1 fragments were amplified by multiplex nested PCR. Then,
      PCR products were processed through an LDR-FMA (ligase detection reaction -
      fluorescent microsphere assay). 23 SNPs, including pvdhfr 57-58-61 and 173,
      pvdhps 382-383, 553, 647 and pvmdr1 976, were simultaneously screened in 366 PNG
      P. vivax samples. RESULTS: Genotyping was successful in 95.4% of the samples for
      at least one gene. The coexistence of multiple distinct haplotypes in the
      parasite population necessitated the introduction of a computer-assisted approach
      to data analysis. Whereas 73.1% of patients were infected with at least one wild
      type genotype at codons 57, 58 and 61 of pvdhfr, a triple mutant genotype was
      detected in 65.6% of the patients, often associated with the 117T mutation. Only
      one patient carried the 173L mutation. The mutant 647P pvdhps genotype allele was
      approaching genetic fixation (99.3%), whereas 35.1% of patients were infected
      with parasites carrying the pvmdr1 976F mutant allele. CONCLUSIONS: The LDR-FMA
      described here allows a discriminant genotyping of resistance alleles in the
      pvdhfr, pvdhps, and pvmdr1 genes and can be used in large-scale surveillance
      studies.

PMID- 21943245
TI  - Multicenter validation of a formula predicting postoperative spinopelvic
      alignment.
AB  - OBJECT: Sagittal spinopelvic imbalance is a major contributor to pain and
      disability for patients with adult spinal deformity (ASD). Preoperative planning
      is essential for pedicle subtraction osteotomy (PSO) candidates; however, current
      methods are often inaccurate because no formula to date predicts both
      postoperative sagittal balance and pelvic alignment. The authors of this study
      aimed to evaluate the accuracy of 2 novel formulas in predicting postoperative
      spinopelvic alignment after PSO. METHODS: This study is a multicenter
      retrospective consecutive PSO case series. Adults with spinal deformity (> 21
      years old) who were treated with a single-level lumbar PSO for sagittal imbalance
      were evaluated. All patients underwent preoperative and a minimum of 6-month
      postoperative radiography. Two novel formulas were used to predict the
      postoperative spinopelvic alignment. The results predicted by the formulas were
      then compared with the actual postoperative radiographic values, and the
      formulas' ability to identify successful (sagittal vertical axis [SVA] <= 50 mm
      and pelvic tilt [PT] <= 25 degrees ) and unsuccessful (SVA > 50 mm or PT > 25
      degrees ) outcomes was evaluated. RESULTS: Ninety-nine patients met inclusion
      criteria. The median absolute error between the predicted and actual PT was 4.1
      degrees  (interquartile range 2.0 degrees -6.4 degrees ). The median absolute
      error between the predicted and actual SVA was 27 mm (interquartile range 11-47
      mm). Forty-one of 54 patients with a formula that predicted a successful outcome
      had a successful outcome as shown by radiography (positive predictive value =
      0.76). Forty-four of 45 patients with a formula that predicted an unsuccessful
      outcome had an unsuccessful outcome as shown by radiography (negative predictive
      value = 0.98). CONCLUSIONS: The spinopelvic alignment formulas were accurate when
      predicting unsuccessful outcomes but less reliable when predicting successful
      outcomes. The preoperative surgical plan should be altered if an unsuccessful
      result is predicted. However, even after obtaining a predicted successful
      outcome, surgeons should ensure that the predicted values are not too close to
      unsuccessful values and should identify other variables that may affect
      alignment. In the near future, it is anticipated that the use of these formulas
      will lead to better surgical planning and improved outcomes for patients with
      complex ASD.

PMID- 21943244
TI  - Xenotropic murine leukemia virus-related virus is not associated with chronic
      fatigue syndrome in patients from different areas of the us in the 1990s.
AB  - BACKGROUND: In 2009, xenotropic murine leukemia virus-related virus (XMRV) was
      reported in 67% of patients with chronic fatigue syndrome (CFS) compared to 4% of
      controls. Since then numerous reports failed to detect XMRV in other cohorts of
      CFS patients, and some studies suggested that XMRV sequences in human samples
      might be due to contamination of these samples with mouse DNA. RESULTS: We
      determined the prevalence of XMRV in patients with CFS from similar areas in the
      United States as the original 2009 study, along with patients with chronic
      inflammatory disorders and healthy persons. Using quantitative PCR, we initially
      detected very low level signals for XMRV DNA in 15% of patients with CFS;
      however, the frequency of PCR positivity was no different between patients with
      CFS and controls. Repeated attempts to isolate PCR products from these reactions
      were unsuccessful. These findings were supported by our observations that PHA and
      IL-2 stimulation of peripheral blood mononuclear cells from patients with
      apparently low levels of XMRV, which induced virus replication in the 2009
      report, resulted in the disappearance of the signal for XMRV DNA in the cells.
      Immunoprecipitation of XMRV-infected cell lysates using serum from patients from
      whom we initially detected low levels of XMRV DNA followed by immunoblotting with
      antibodies to XMRV gp70 protein failed to detect antibody in the patients,
      although one control had a weak level of reactivity. Diverse murine leukemia
      virus (MLV) sequences were obtained by nested PCR with a similar frequency in CFS
      patients and controls. Finally, we did not detect XMRV sequences in patients with
      several chronic inflammatory disorders including rheumatoid arthritis, Bechet's
      disease, and systemic lupus erythematosus. CONCLUSIONS: We found no definitive
      evidence for XMRV DNA sequences or antibody in our cohort of CFS patients, which
      like the original 2009 study, included patients from diverse regions of the
      United States. In addition, XMRV was not detected in a cohort of patients with
      chronic inflammatory disorders.

PMID- 21943246
TI  - Traumatic sacral pseudomeningocele with spina bifida occulta.
AB  - Pseudomeningocele arises after spinal fracture and nerve root avulsion or after
      complications of spine surgery. However, traumatic pseudomeningocele with spina
      bifida occulta is rare. In this report, a traumatic pseudomeningocele in a
      patient with spina bifida occulta that required surgical treatment is documented.
      This 37-year-old man presented to the authors' hospital with headache and a
      fluctuant mass in the center of his buttocks. A CT scan with myelography and MR
      imaging of the sacral region revealed a large subcutaneous area of fluid
      retention communicating with the intradural space through a defect of the S-2
      lamina. Because 3 months of conservative treatment was unsuccessful, a free fat
      graft was placed with fibrin glue to seal the closure of the defect, followed by
      1 week of CSF drainage. This is the first report on traumatic pseudomeningocele
      with spina bifida occulta successfully treated in this manner.

PMID- 21943247
TI  - Editorial: traumatic sacral pseudomeningocele.

PMID- 21943248
TI  - How recombinant swollenin from Kluyveromyces lactis affects cellulosic substrates
      and accelerates their hydrolysis.
AB  - BACKGROUND: In order to generate biofuels, insoluble cellulosic substrates are
      pretreated and subsequently hydrolyzed with cellulases. One way to pretreat
      cellulose in a safe and environmentally friendly manner is to apply, under mild
      conditions, non-hydrolyzing proteins such as swollenin - naturally produced in
      low yields by the fungus Trichoderma reesei. To yield sufficient swollenin for
      industrial applications, the first aim of this study is to present a new way of
      producing recombinant swollenin. The main objective is to show how swollenin
      quantitatively affects relevant physical properties of cellulosic substrates and
      how it affects subsequent hydrolysis. RESULTS: After expression in the yeast
      Kluyveromyces lactis, the resulting swollenin was purified. The adsorption
      parameters of the recombinant swollenin onto cellulose were quantified for the
      first time and were comparable to those of individual cellulases from T. reesei.
      Four different insoluble cellulosic substrates were then pretreated with
      swollenin. At first, it could be qualitatively shown by macroscopic evaluation
      and microscopy that swollenin caused deagglomeration of bigger cellulose
      agglomerates as well as dispersion of cellulose microfibrils (amorphogenesis).
      Afterwards, the effects of swollenin on cellulose particle size, maximum
      cellulase adsorption and cellulose crystallinity were quantified. The
      pretreatment with swollenin resulted in a significant decrease in particle size
      of the cellulosic substrates as well as in their crystallinity, thereby
      substantially increasing maximum cellulase adsorption onto these substrates.
      Subsequently, the pretreated cellulosic substrates were hydrolyzed with
      cellulases. Here, pretreatment of cellulosic substrates with swollenin, even in
      non-saturating concentrations, significantly accelerated the hydrolysis. By
      correlating particle size and crystallinity of the cellulosic substrates with
      initial hydrolysis rates, it could be shown that the swollenin-induced reduction
      in particle size and crystallinity resulted in high cellulose hydrolysis rates.
      CONCLUSIONS: Recombinant swollenin can be easily produced with the robust yeast
      K. lactis. Moreover, swollenin induces deagglomeration of cellulose agglomerates
      as well as amorphogenesis (decrystallization). For the first time, this study
      quantifies and elucidates in detail how swollenin affects different cellulosic
      substrates and their hydrolysis.

PMID- 21943249
TI  - Functional characterization of the Saccharomyces cerevisiae protein Chl1 reveals
      the role of sister chromatid cohesion in the maintenance of spindle length during
      S-phase arrest.
AB  - BACKGROUND: Metaphase cells have short spindles for efficient bi-orientation of
      chromosomes. The cohesin proteins hold sister chromatids together, creating
      Sister Chromatid Cohesion (SCC) that helps in the maintenance of short spindle
      lengths in metaphase. The budding yeast protein Chl1p, which has human homologs,
      is required for DNA damage repair, recombination, transcriptional silencing and
      aging. This protein is also needed to establish SCC between sister chromatids in
      S-phase. RESULTS: In the present study we have further characterized Chl1p for
      its role in the yeast Saccharomyces cerevisiae when cells are under replication
      stress. We show that when DNA replication is arrested by hydroxyurea (HU), the
      chl1 mutation causes growth deficiency and a mild loss in cell viability.
      Although both mutant and wild-type cells remained arrested with undivided nuclei,
      mutant cells had mitotic spindles, which were about 60-80% longer than wild-type
      spindles. Spindle extension occurred in S-phase in the presence of an active S
      phase checkpoint pathway. Further, the chl1 mutant did not show any kinetochore
      related defect that could have caused spindle extension. These cells were
      affected in the retention of SCC in that they had only about one-fourth of the
      normal levels of the cohesin subunit Scc1p at centromeres, which was sufficient
      to bi-orient the chromosomes. The mutant cells showed defects in SCC, both during
      its establishment in S-phase and in its maintenance in G2. Mutants with partial
      and pericentromeric cohesion defects also showed spindle elongation when arrested
      in S-phase by HU. CONCLUSIONS: Our work shows that Chl1p is required for normal
      growth and cell viability in the presence of the replication block caused by HU.
      The absence of this protein does not, however, compromize the replication
      checkpoint pathway. Even though the chl1 mutation gives synthetic lethal
      interactions with kinetochore mutations, its absence does not affect kinetochore
      function; kinetochore-microtubule interactions remain unperturbed. Further, chl1
      cells were found to lose SCC at centromeres in both S- and G2 phases, showing the
      requirement of Chl1p for the maintenance of cohesion in G2 phase of these cells.
      This work documents for the first time that SCC is an important determinant of
      spindle size in the yeast Saccharomyces cerevisiae when genotoxic agents cause S
      phase arrest of cells.

PMID- 21943251
TI  - Contact allergy to the 26 specific fragrance ingredients to be declared on
      cosmetic products in accordance with the EU cosmetics directive.
AB  - BACKGROUND: Fragrance ingredients are a frequent cause of allergic contact
      dermatitis. The EU Cosmetics Directive states that 26 specific fragrance
      ingredients, known to cause allergic contact dermatitis, must be declared on the
      ingredient lists of cosmetic products. OBJECTIVES: To investigate frequencies of
      sensitization to the 26 individual fragrances and evaluate their importance as
      screening markers of fragrance allergy. METHOD: This was a retrospective study
      based on data from the Department of Dermato-Allergology, Copenhagen University
      Hospital Gentofte. Eczema patients (n = 1508) were patch tested (January 2008 to
      July 2010) with the 26 fragrance ingredients. RESULTS: Sensitization to the 26
      fragrances was identified in 115 (7.6%) subjects. The most frequent allergens
      were Evernia furfuracea (n = 50), Evernia prunastri (n = 31), and hydroxyisohexyl
      3-cyclohexene carboxaldehyde (n = 24). Including fragrance mix I, fragrance mix
      II and Myroxylon pereirae, 196 (13.0%) had a fragrance allergy. Testing with the
      26 fragrances additionally identified 23 subjects who would otherwise have gone
      undetected. The majority (75.7%) of positive reactions to the 26 fragrances were
      of clinical relevance. CONCLUSIONS: Sensitization to the 26 individual fragrance
      ingredients was identified in 7.6% of the subjects patch tested. Most reactions
      were of clinical relevance. Fragrance-allergic subjects would be missed if
      testing with the individual fragrance ingredients was not performed.

PMID- 21943252
TI  - Use of peer assessment as a student engagement strategy in nurse education.
AB  - This paper describes how peer assessment was implemented in an undergraduate
      nursing program in Ireland to enhance student engagement, and reports students'
      (n=37) experiences of the process. The process involved second year Bachelor of
      Nursing Science students developing marking criteria and marking two of their
      colleagues' assignments anonymously. A qualitative descriptive design using focus
      group interviews was used to collect data on students' experiences. Demographic
      data were collected through questionnaires. The analysis identified three themes:
      (i) impact on student engagement; (ii) challenges of peer assessment; and (iii)
      making it better. The findings revealed that most students enjoyed the process,
      and that peer assessment facilitates and enhances student engagement. The
      findings also provide evidence to support the self-regulation theory of learning.
      A detailed account of the methods used to implement peer assessment is also
      provided, which might be useful for other nurse educators seeking to implement
      peer assessment at an undergraduate level.

PMID- 21943250
TI  - ABCG2 is associated with HER-2 expression, lymph node metastasis and clinical
      stage in breast invasive ductal carcinoma.
AB  - BACKGROUND: ABCG2 is an ABC transporter. It has been demonstrated that endogenous
      ABCG2 expression in certain cancers is a possible reflection of the
      differentiated phenotype of the cell of origin and likely contributes to
      intrinsic drug resistance. But little is known about the contribution of ABCG2 to
      the drug resistance and the clinicopathological characteristics in breast cancer.
      In the present study, we investigated the expression of ABCG2 and the
      correlations between ABCG2 expression and patients' clinicopathological and
      biological characteristics. METHODS: Immunohistochemistry was employed on the
      tissue microarray paraffin sections of surgically removed samples from 196 breast
      cancer patients with clinicopathological data. RESULTS: The results showed that
      ABCG2 was expressed in different intensities and distributions in the tumor cells
      of the breast invasive ductal carcinoma. A positive stain for ABCG2 was defined
      as a brown stain observed in the cytoplasm and cytomembrane. A statistically
      significant correlation was demonstrated between ABCG2 expression and HER-2
      expression (p = 0.001), lymph node metastasis (p = 0.049), and clinical stage (p
      = 0.015) respectively. CONCLUSION: ABCG2 correlated with Her-2 expression, lymph
      node metastasis and clinical stage in breast invasive ductal carcinoma. It could
      be a novel potential bio-marker which can predict biological behavior, clinical
      progression, prognosis and chemotherapy effectiveness.

PMID- 21943253
TI  - The NAC domain-containing protein, GmNAC6, is a downstream component of the ER
      stress- and osmotic stress-induced NRP-mediated cell-death signaling pathway.
AB  - BACKGROUND: The endoplasmic reticulum (ER) is a major signaling organelle, which
      integrates a variety of responses against physiological stresses. In plants, one
      such stress-integrating response is the N-rich protein (NRP)-mediated cell death
      signaling pathway, which is synergistically activated by combined ER stress and
      osmotic stress signals. Despite the potential of this integrated signaling to
      protect plant cells against different stress conditions, mechanistic knowledge of
      the pathway is lacking, and downstream components have yet to be identified.
      RESULTS: In the present investigation, we discovered an NAC domain-containing
      protein from soybean, GmNAC6 (Glycine max NAC6), to be a downstream component of
      the integrated pathway. Similar to NRP-A and NRP-B, GmNAC6 is induced by ER
      stress and osmotic stress individually, but requires both signals for full
      activation. Transient expression of GmNAC6 promoted cell death and hypersensitive
      like responses in planta. GmNAC6 and NRPs also share overlapping responses to
      biotic signals, but the induction of NRPs peaked before the increased
      accumulation of GmNAC6 transcripts. Consistent with the delayed kinetics of
      GmNAC6 induction, increased levels of NRP-A and NRP-B transcripts induced
      promoter activation and the expression of the GmNAC6 gene. CONCLUSIONS:
      Collectively, our results biochemically link GmNAC6 to the ER stress- and osmotic
      stress-integrating cell death response and show that GmNAC6 may act downstream of
      the NRPs.

PMID- 21943254
TI  - What is the potential of oligodendrocyte progenitor cells to successfully treat
      human spinal cord injury?
AB  - BACKGROUND: Spinal cord injury is a serious and debilitating condition, affecting
      millions of people worldwide. Long seen as a permanent injury, recent advances in
      stem cell research have brought closer the possibility of repairing the spinal
      cord. One such approach involves injecting oligodendrocyte progenitor cells,
      derived from human embryonic stem cells, into the injured spinal cord in the hope
      that they will initiate repair. A phase I clinical trial of this therapy was
      started in mid 2010 and is currently underway. DISCUSSION: The theory underlying
      this approach is that these myelinating progenitors will phenotypically replace
      myelin lost during injury whilst helping to promote a repair environment in the
      lesion. However, the importance of demyelination in the pathogenesis of human
      spinal cord injury is a contentious issue and a body of literature suggests that
      it is only a minor factor in the overall injury process. SUMMARY: This review
      examines the validity of the theory underpinning the on-going clinical trial as
      well as analysing published data from animal models and finally discussing issues
      surrounding safety and purity in order to assess the potential of this approach
      to successfully treat acute human spinal cord injury.

PMID- 21943255
TI  - Gender differences in response to cold pressor test assessed with velocity
      encoded cardiovascular magnetic resonance of the coronary sinus.
AB  - BACKGROUND: Gender-specific differences in cardiovascular risk are well known,
      and current evidence supports an existing role of endothelium in these
      differences. The purpose of this study was to assess non invasively coronary
      endothelial function in male and female young volunteers by myocardial blood flow
      (MBF) measurement using coronary sinus (CS) flow quantification by velocity
      encoded cine cardiovascular magnetic resonance (CMR) at rest and during cold
      pressor test (CPT). METHODS: Twenty-four healthy volunteers (12 men, 12 women)
      underwent CMR in a 3 Tesla MR imager. Coronary sinus flow was measured at rest
      and during CPT using non breath-hold velocity encoded phase contrast cine-CMR.
      Myocardial function and morphology were acquired using a cine steady-state free
      precession sequence. RESULTS: At baseline, mean MBF was 0.63 +/- 0.23 mL.g-1.min
      1 in men and 0.79 +/- 0.21 mL.g-1.min-1 in women. During CPT, the rate pressure
      product in men significantly increased by 49 +/- 36% (p < 0.0001) and in women by
      52 +/- 22% (p < 0.0001). MBF increased significantly in both men and women by
      0.22 +/- 0.19 mL.g-1.min-1 (p = 0.0022) and by 0.73 +/- 0.43 mL.g-1.min-1 (p =
      0.0001), respectively. The increase in MBF was significantly higher in women than
      in men (p = 0.0012). CONCLUSION: CMR coronary sinus flow quantification for
      measuring myocardial blood flow revealed a higher response of MBF to CPT in women
      than in men. This finding may reflect gender differences in endothelial-dependent
      vasodilatation in these young subjects. This non invasive rest/stress protocol
      may become helpful to study endothelial function in normal physiology and in
      physiopathology.

PMID- 21943256
TI  - Detailed kinetics and regulation of mammalian 2-oxoglutarate dehydrogenase.
AB  - BACKGROUND: Mitochondrial 2-oxoglutarate (alpha-ketoglutarate) dehydrogenase
      complex (OGDHC), a key regulatory point of tricarboxylic acid (TCA) cycle, plays
      vital roles in multiple pathways of energy metabolism and biosynthesis. The
      catalytic mechanism and allosteric regulation of this large enzyme complex are
      not fully understood. Here computer simulation is used to test possible catalytic
      mechanisms and mechanisms of allosteric regulation of the enzyme by nucleotides
      (ATP, ADP), pH, and metal ion cofactors (Ca(2+) and Mg(2+)). RESULTS: A model was
      developed based on an ordered ter-ter enzyme kinetic mechanism combined with con
      formational changes that involve rotation of one lipoic acid between three
      catalytic sites inside the enzyme complex. The model was parameterized using a
      large number of kinetic data sets on the activity of OGDHC, and validated by
      comparison of model predictions to independent data. CONCLUSIONS: The developed
      model suggests a hybrid rapid-equilibrium ping-pong random mechanism for the
      kinetics of OGDHC, consistent with previously reported mechanisms, and accurately
      describes the experimentally observed regulatory effects of cofactors on the
      OGDHC activity. This analysis provides a single consistent theoretical
      explanation for a number of apparently contradictory results on the roles of
      phosphorylation potential, NAD (H) oxidation-reduction state ratio, as well as
      the regulatory effects of metal ions on ODGHC function.

PMID- 21943258
TI  - The use of prisoners as sources of organs--an ethically dubious practice.
AB  - The movement to try to close the ever-widening gap between demand and supply of
      organs has recently arrived at the prison gate. While there is enthusiasm for
      using executed prisoners as sources of organs, there are both practical barriers
      and moral concerns that make it unlikely that proposals to use prisoners will or
      should gain traction. Prisoners are generally not healthy enough to be a safe
      source of organs, execution makes the procurement of viable organs difficult, and
      organ donation post-execution ties the medical profession too closely to the act
      of execution.

PMID- 21943257
TI  - Early response predicts subsequent response to olanzapine long-acting injection
      in a randomized, double-blind clinical trial of treatment for schizophrenia.
AB  - BACKGROUND: In patients with schizophrenia, early non-response to oral
      antipsychotic therapy robustly predicts subsequent non-response to continued
      treatment with the same medication. This study assessed whether early response
      predicted later response when using a long-acting injection (LAI) antipsychotic.
      METHODS: Data were taken from an 8-week, randomized, double-blind, placebo
      controlled study of olanzapine LAI in acutely ill patients with schizophrenia (n
      = 233). Early response was defined as >= 30% improvement from baseline to Week 4
      in Positive and Negative Syndrome Scale (PANSS0-6) Total score. Subsequent
      response was defined as >= 40% baseline-to-endpoint improvement in PANSS0-6 Total
      score. Sensitivity, specificity, positive predictive value (PPV), negative
      predictive value (NPV), and predictive accuracy were calculated. Clinical and
      functional outcomes were compared between Early Responders and Early Non
      responders. RESULTS: Early response/non-response to olanzapine LAI predicted
      later response/non-response with high sensitivity (85%), specificity (72%), PPV
      (78%), NPV (80%), and overall accuracy (79%). Compared to Early Non-responders,
      Early Responders had significantly greater improvement in PANSS0-6 Total scores
      at all time points and greater baseline-to-endpoint improvement in PANSS subscale
      scores, Quality of Life Scale scores, and Short Form-36 Health Survey scores (all
      p <= .01). Among Early Non-responders, 20% demonstrated response by Week 8.
      Patients who lacked early improvement (at Week 4) in Negative Symptoms and
      Disorganized Thoughts were more likely to continue being non-responders at Week
      8. CONCLUSIONS: Among acutely ill patients with schizophrenia, early response
      predicted subsequent response to olanzapine LAI. Early Responders experienced
      significantly better clinical and functional outcomes than Early Non-responders.
      Findings are consistent with previous research on oral antipsychotics. CLINICAL
      TRIALS REGISTRY: F1D-MC-HGJZ: Comparison of Intramuscular Olanzapine Depot With
      Placebo in the Treatment of Patients With Schizophrenia
      http://clinicaltrials.gov/ct2/show/NCT00088478?term=olanzapine+depot&rank=3Regist
      y identifier - NCT00088478.

PMID- 21943259
TI  - What it means to treat people as ends-in-themselves.

PMID- 21943260
TI  - Retribution, deterrence, and organ donation.

PMID- 21943261
TI  - The ethically dubious practice of thwarting the redemption of the condemned.

PMID- 21943262
TI  - Organs by firing squad: the medical and moral implausibility of death penalty
      organ procurement.

PMID- 21943263
TI  - Would donation undercut the morality of execution?

PMID- 21943264
TI  - Prisoners as living organ donors: the case of the Scott sisters.

PMID- 21943265
TI  - Criteria for authorship in bioethics.
AB  - Multiple authorship is becoming increasingly common in bioethics research. There
      are well-established criteria for authorship in empirical bioethics research but
      not for conceptual research. It is important to develop criteria for authorship
      in conceptual publications to prevent undeserved authorship and uphold standards
      of fairness and accountability. This article explores the issue of multiple
      authorship in bioethics and develops criteria for determining who should be an
      author on a conceptual publication in bioethics. Authorship in conceptual
      research should be based on contributing substantially to: (1) identifying a
      topic, problem, or issue to study; (2) reviewing and interpreting the relevant
      literature; (3) formulating, analyzing, and evaluating arguments that support one
      or more theses; (4) responding to objections and counterarguments; and (5)
      drafting the manuscript. Authors of conceptual publications should participate
      substantially in at least two of areas (1)-(5) and also approve the final
      version. [corrected].

PMID- 21943266
TI  - Bioethics authorship in context: how trends in biomedicine challenge bioethics.

PMID- 21943267
TI  - What about author order and acknowledgments? Suggestions for additional criteria
      for conceptual research in bioethics.

PMID- 21943268
TI  - How authorship guidelines in bioethics can ensure fairness and accountability.

PMID- 21943269
TI  - But what does authorship mean, indeed?

PMID- 21943270
TI  - Is multiple authorship in conceptual bioethics ethically sustainable?

PMID- 21943271
TI  - On authorship.

PMID- 21943272
TI  - Letter to the editors.

PMID- 21943277
TI  - Response to open peer commentaries on "Rationing just medical care".

PMID- 21943278
TI  - High beverage sugar as well as high animal protein intake at infancy may increase
      overweight risk at 8 years: a prospective longitudinal pilot study.
AB  - BACKGROUND: Combined effects of early exposure to beverage sugar and animal
      protein and later life overweight risk have not been studied. METHODS: A
      prospective longitudinal study was initiated in 2001 with 226 infants between 4
      and 13 months of age. Dietary intake was assessed with a 2 day food record. Also
      information on infant body weight and socio-economic status was obtained at
      baseline. At 8 year follow-up in 2009, children were surveyed again. Main outcome
      measure was overweight at 8 years as defined by BMIsds > = +1.0. Also maternal
      BMI, present dietary intake and physical activity, were obtained by questionnaire
      and 2-day food record. RESULTS: At the 8 year follow up, 120 children (53%) were
      surveyed again. Of those, questionnaires and food records were completed for 63
      children, for the other 57 children only weight and height at 8 years was
      available; 20 out of 120 children (17%) were self-reported overweight at 8 years
      of age. Unadjusted odds ratios (ORs; 95% CI) for overweight at 8 years were 1.10
      (1.02, 1.18) for beverage sugar intake per one percent of energy intake and 4.06
      (1.50, 11.00) for the highest tertile of animal protein intake at infancy
      compared to the lowest two tertiles. After adjustment for sex, age, infant
      weight, breastfed at intake assessment, and socio-economic status, odds ratios
      were 1.13 (1.03, 1.24) for beverage sugar, and 9.67 (2.56, 36.53) for highest
      tertile of animal protein intake. In the subgroup with completed questionnaire (n
      = 63) ORs were also adjusted for current maternal overweight, more than 2 months
      full breastfeeding, physical activity, and energy intake, but ORs remained
      significantly associated with overweight at 8 years. CONCLUSIONS: A high intake
      of sugar containing beverages as well as animal protein in the first year of life
      may increase the risk of overweight at 8 years. The results of this pilot
      investigation should be confirmed in a larger cohort.

PMID- 21943279
TI  - Mouse mammary tumor virus-like gene sequences are present in lung patient
      specimens.
AB  - BACKGROUND: Previous studies have reported on the presence of Murine Mammary
      Tumor Virus (MMTV)-like gene sequences in human cancer tissue specimens. Here, we
      search for MMTV-like gene sequences in lung diseases including carcinomas
      specimens from a Mexican population. This study was based on our previous study
      reporting that the INER51 lung cancer cell line, from a pleural effusion of a
      Mexican patient, contains MMTV-like env gene sequences. RESULTS: The MMTV-like
      env gene sequences have been detected in three out of 18 specimens studied, by
      PCR using a specific set of MMTV-like primers. The three identified MMTV-like
      gene sequences, which were assigned as INER6, HZ101, and HZ14, were 99%, 98%, and
      97% homologous, respectively, as compared to GenBank sequence accession number
      AY161347. The INER6 and HZ-101 samples were isolated from lung cancer specimens,
      and the HZ-14 was isolated from an acute inflammatory lung infiltrate sample. Two
      of the env sequences exhibited disruption of the reading frame due to mutations.
      CONCLUSION: In summary, we identified the presence of MMTV-like gene sequences in
      2 out of 11 (18%) of the lung carcinomas and 1 out of 7 (14%) of acute
      inflamatory lung infiltrate specimens studied of a Mexican Population.

PMID- 21943280
TI  - Non-therapeutic administration of a model antimicrobial growth promoter modulates
      intestinal immune responses.
AB  - BACKGROUND: The development of efficacious alternatives to antimicrobial growth
      promoters (AGP) in livestock production is an urgent issue, but is hampered by a
      lack of knowledge regarding the mode of action of AGP. The belief that AGP
      modulate the intestinal microbiota has become prominent in the literature;
      however, there is a lack of experimental evidence to support this hypothesis.
      Using a chlortetracycline-murine-Citrobacter rodentium model, the ability of AGP
      to modulate the intestinal immune system in mammals was investigated. RESULTS: C.
      rodentium was transformed with the tetracycline resistance gene, tetO, and
      continuous oral administration of a non-therapeutic dose of chlortetracycline to
      mice did not affect densities of C. rodentium CFU in feces throughout the
      experiment or associated with mucosal surfaces in the colon (i.e. at peak and
      late infection). However, chlortetracycline regulated transcription levels of Th1
      and Th17 inflammatory cytokines in a temporal manner in C. rodentium-inoculated
      mice, and ameliorated weight loss associated with infection. In mice inoculated
      with C. rodentium, those that received chlortetracycline had less pathologic
      changes in the distal colon than mice not administered CTC (i.e. relative to
      untreated mice). Furthermore, chlortetracycline administration at a non
      therapeutic dose did not impart either prominent or consistent effects on the
      colonic microbiota. CONCLUSION: Data support the hypothesis that AGP function by
      modulating the intestinal immune system in mammals. This finding may facilitate
      the development of biorationale-based and efficacious alternatives to AGP.

PMID- 21943281
TI  - More mentoring needed? A cross-sectional study of mentoring programs for medical
      students in Germany.
AB  - BACKGROUND: Despite increasing recognition that mentoring is essential early in
      medical careers, little is known about the prevalence of mentoring programs for
      medical students. We conducted this study to survey all medical schools in
      Germany regarding the prevalence of mentoring programs for medical students as
      well as the characteristics, goals and effectiveness of these programs. METHODS:
      A definition of mentoring was established and program inclusion criteria were
      determined based on a review of the literature. The literature defined mentoring
      as a steady, long-lasting relationship designed to promote the mentee's overall
      development. We developed a questionnaire to assess key characteristics of
      mentoring programs: the advocated mentoring model, the number of participating
      mentees and mentors, funding and staff, and characteristics of mentees and
      mentors (e.g., level of training). In addition, the survey characterized the
      mentee-mentor relationship regarding the frequency of meetings, forms of
      communication, incentives for mentors, the mode of matching mentors and mentees,
      and results of program evaluations. Furthermore, participants were asked to
      characterize the aims of their programs. The questionnaire consisted of 34
      questions total, in multiple-choice (17), numeric (7) and free-text (10) format.
      This questionnaire was sent to deans and medical education faculty in Germany
      between June and September 2009. For numeric answers, mean, median, and standard
      deviation were determined. For free-text items, responses were coded into
      categories using qualitative free text analysis. RESULTS: We received responses
      from all 36 medical schools in Germany. We found that 20 out of 36 medical
      schools in Germany offer 22 active mentoring programs with a median of 125 and a
      total of 5,843 medical students (6.9 - 7.4% of all German medical students)
      enrolled as mentees at the time of the survey. 14 out of 22 programs (63%) have
      been established within the last 2 years. Six programs (27%) offer mentoring in a
      one-on-one setting. 18 programs (82%) feature faculty physicians as mentors. Nine
      programs (41%) involve students as mentors in a peer-mentoring setting. The most
      commonly reported goals of the mentoring programs include: establishing the
      mentee's professional network (13 programs, 59%), enhancement of academic
      performance (11 programs, 50%) and counseling students in difficulties (10
      programs, 45%). CONCLUSIONS: Despite a clear upsurge of mentoring programs for
      German medical students over recent years, the overall availability of mentoring
      is still limited. The mentoring models and goals of the existing programs vary
      considerably. Outcome data from controlled studies are needed to compare the
      efficiency and effectiveness of different forms of mentoring for medical
      students.

PMID- 21943282
TI  - Street-outreach improves detection but not referral for drug users with latent
      tuberculosis, New York City.
AB  - Street outreach in two New York City communities, Harlem and the South Bronx,
      between May 2001 and March 2003, provided tuberculin skin test (TST) screening to
      illicit drug users outside the traditional health care system. Persons who used
      heroin, cocaine, and/or crack were offered a TST, incentives to return for TST
      reading, and further evaluation if TST was positive. Of 809 participants, 530
      (66%) accepted a TST and 81% (429/530) returned for TST reading. Of 429
      participants, 40 (9%) were TST positive. Participants found TST positive did not
      differ from those found TST negative in previous drug user treatment or drug use
      practices including snorting heroin, sniffing cocaine, smoking crack, and
      injecting drugs of any kind. Of the 40 participants found TST positive, the 21
      who tested TST positive for the first time were more likely to be male (p = .03)
      and noninjectors (p = .02), than the 19 who had tested TST positive in the past.
      Only two newly identified persons pursued follow-up care. Street recruitment
      expanded testing. Better follow-up strategies are needed. The study's limitations
      are noted.

PMID- 21943283
TI  - Methodological approach for the assessment of ultrasound reproducibility of
      cardiac structure and function: a proposal of the study group of Echocardiography
      of the Italian Society of Cardiology (Ultra Cardia SIC) part I.
AB  - When applying echo-Doppler imaging for either clinical or research purposes it is
      very important to select the most adequate modality/technology and choose the
      most reliable and reproducible measurements. Quality control is a mainstay to
      reduce variability among institutions and operators and must be obtained by using
      appropriate procedures for data acquisition, storage and interpretation of echo
      Doppler data. This goal can be achieved by employing an echo core laboratory
      (ECL), with the responsibility for standardizing image acquisition processes
      (performed at the peripheral echo-labs) and analysis (by monitoring and
      optimizing the internal intra- and inter-reader variability of measurements).
      Accordingly, the Working Group of Echocardiography of the Italian Society of
      Cardiology decided to design standardized procedures for imaging acquisition in
      peripheral laboratories and reading procedures and to propose a methodological
      approach to assess the reproducibility of echo-Doppler parameters of cardiac
      structure and function by using both standard and advanced technologies. A number
      of cardiologists experienced in cardiac ultrasound was involved to set up an ECL
      available for future studies involving complex imaging or including echo-Doppler
      measures as primary or secondary efficacy or safety end-points. The present
      manuscript describes the methodology of the procedures (imaging acquisition and
      measurement reading) and provides the documentation of the work done so far to
      test the reproducibility of the different echo-Doppler modalities (standard and
      advanced). These procedures can be suggested for utilization also in non referall
      echocardiographic laboratories as an "inside" quality check, with the aim at
      optimizing clinical consistency of echo-Doppler data.

PMID- 21943284
TI  - Inhibition of protein kinase C promotes differentiation of neuroblastoma * glioma
      NG108-15 hybrid cells.
AB  - Differentiation of neuroblastoma * glioma NG108-15 hybrid cells can be induced by
      different means, but the mechanisms involved are unclear. Our aim was to
      characterize the role of protein kinase C (PKC) in this process. The PKCs present
      in NG108-15 cells, i.e. PKCalpha, PKCdelta, PKCepsilon and PKCzeta, were
      inhibited using a cocktail of Go6983 and Ro318220 or were downregulated by
      treatment with phorbol 12-myristate 13-acetate (PMA). In high-glucose Dulbecco's
      modified Eagle medium, neuritogenesis was induced by 24 h treatment with a
      cocktail of Go6983 and Ro318220 or by 48 h treatment with PMA, the latter process
      thus requiring a longer treatment. However, when cells treated with PMA for only
      24 h were placed in extracellular standard salts solution, e.g. Locke's buffer,
      for 3 h, morphological and functional differentiation occurred, with rounding of
      the cell body, actin polymerization subjacent to the plasma membrane and an
      increase in voltage-sensitive Ca(2+)  channel activity in the absence of cell
      death. This rapid differentiation was not due to autophagy, growth arrest or
      increased cyclic AMP response element binding protein phosphorylation, but
      coincided with combined activation of p38 mitogen-activated protein kinase (MAPK)
      and inhibition of extracellular signal-regulated kinase (ERK) and Akt, as
      confirmed by the effects of selective inhibitors. Furthermore, PKC activation
      blocked thapsigargin-induced neuritogenesis, whereas PKC downregulation did not.
      These results show that PKC downregulation promotes differentiation and this
      effect is accelerated by exposure to Locke's buffer. Although this experimental
      paradigm cannot be related to the in vivo situation and disease, it implies that
      combined inhibition of Akt and p44/p42 ERK and activation of p38 MAPK promotes
      differentiation.

PMID- 21943285
TI  - Using 'may contain' labelling to inform food choice: a qualitative study of nut
      allergic consumers.
AB  - BACKGROUND: Precautionary 'may contain' warnings are used to indicate possible
      allergen contamination. Neither food safety nor foods labelling legislation
      address this issue. The aim of this study is to understand how peanut and nut
      allergic adults interpret 'may contain' labelling and how they use this
      information when purchasing food. METHODS: Qualitative methods were used to
      explore both behaviour and attitudes. The behaviour and 'thinking aloud' of 32
      participants were recorded during their normal food shop. A semi-structured
      interview also explored participants' views about 13 potentially problematic
      packaged foods. Transcribed data from these tasks were analysed to explore the
      interpretation of 'may contain' labelling and how this influenced food choice
      decisions. RESULTS: Peanut and nut allergic individuals adopt a complex range of
      responses and strategies to interpret 'may contain' labelling. Many claimed such
      labelling was not credible or desirable; many ignored it whilst some found it
      helpful and avoided products with all such labelling. Interpretation and
      consequent decisions were not only based on the detail of the labelling but also
      on external factors such as the nature of the product, the perceived
      trustworthiness of the producer and on the previous experience of the nut
      allergic individual. CONCLUSIONS: 'May contain' labelling was interpreted in the
      light of judgements about the product, producer and previous personal experience.
      It is vital that these interpretation strategies are taken into account by those
      responsible for labelling itself and for the provision of advice to nut allergic
      individuals. Suggestions to improve labelling and advice to the allergic
      individual are considered.

PMID- 21943286
TI  - Decreased expression of B cell related genes in leukocytes of women with
      Parkinson's disease.
AB  - BACKGROUND: Parkinson's disease (PD) is a complex disorder caused by genetic,
      environmental and age-related factors, and it is more prevalent in men. We aimed
      to identify differentially expressed genes in peripheral blood leukocytes (PBLs)
      that might be involved in PD pathogenesis. Transcriptomes of 30 female PD
      patients and 29 age- and sex-matched controls were profiled using GeneChip Human
      Exon 1.0 ST Arrays. Samples were from unrelated Ashkenazi individuals, non
      carriers of LRRK2 G2019S or GBA founder mutations. RESULTS: Differential
      expression was detected in 115 genes (206 exons), with over-representation of
      immune response annotations. Thirty genes were related to B cell functions,
      including the uniquely B cell-expressed IGHM and IGHD, the B cell surface
      molecules CD19, CD22 and CD79A, and the B cell gene regulator, PAX5. Quantitative
      RT-PCR confirmation of these 6 genes in 79 individuals demonstrated decreased
      expression, mainly in women patients, independent of PD-pharmacotherapy status.
      CONCLUSIONS: Our results suggest that the down regulation of genes related to B
      cell activity reflect the involvement of these cells in PD in Ashkenazi
      individuals and represents a molecular aspect of gender-specificity in PD.

PMID- 21943287
TI  - Biogenic hydrogen and methane production from Chlorella vulgaris and Dunaliella
      tertiolecta biomass.
AB  - BACKGROUND: Microalgae are a promising feedstock for biofuel and bioenergy
      production due to their high photosynthetic efficiencies, high growth rates and
      no need for external organic carbon supply. In this study, utilization of
      Chlorella vulgaris (a fresh water microalga) and Dunaliella tertiolecta (a marine
      microalga) biomass was tested as a feedstock for anaerobic H2 and CH4 production.
      RESULTS: Anaerobic serum bottle assays were conducted at 37 degrees C with
      enrichment cultures derived from municipal anaerobic digester sludge. Low levels
      of H2 were produced by anaerobic enrichment cultures, but H2 was subsequently
      consumed even in the presence of 2-bromoethanesulfonic acid, an inhibitor of
      methanogens. Without inoculation, algal biomass still produced H2 due to the
      activities of satellite bacteria associated with algal cultures. CH4 was produced
      from both types of biomass with anaerobic enrichments. Polymerase chain reaction
      denaturing gradient gel electrophoresis profiling indicated the presence of H2
      producing and H2-consuming bacteria in the anaerobic enrichment cultures and the
      presence of H2-producing bacteria among the satellite bacteria in both sources of
      algal biomass. CONCLUSIONS: H2 production by the satellite bacteria was
      comparable from D. tertiolecta (12.6 ml H2/g volatile solids (VS)) and from C.
      vulgaris (10.8 ml H2/g VS), whereas CH4 production was significantly higher from
      C. vulgaris (286 ml/g VS) than from D. tertiolecta (24 ml/g VS). The high
      salinity of the D. tertiolecta slurry, prohibitive to methanogens, was the
      probable reason for lower CH4 production.

PMID- 21943288
TI  - Plant use in Odo-Bulu and Demaro, Bale region, Ethiopia.
AB  - This paper reports on the plant use of laypeople of the Oromo in Southern
      Ethiopia. The Oromo in Bale had names/uses for 294 species in comparison to 230
      species documented in the lower reaches of the Bale area. Only 13 species was
      used for veterinary purposes, or as human medicine (46). Plant medicine served
      mostly to treat common everyday ailments such as stomach problems and diarrhea,
      for wound treatment and as toothbrush-sticks, as anthelmintic, for skin
      infections and to treat sore muscles and. Interestingly, 9 species were used to
      treat spiritual ailments and to expel demons. In most cases of medicinal
      applications the leaves or roots were employed.Traditional plant knowledge has
      clearly declined in a large part of the research area. Western style health care
      services as provided by governments and NGOs, in particular in rural areas, seem
      to have contributed to a decline in traditional knowledge, in part because the
      local population simply regards western medicine as more effective and safer.

PMID- 21943289
TI  - Transcriptome profiling of immune responses to cardiomyopathy syndrome (CMS) in
      Atlantic salmon.
AB  - BACKGROUND: Cardiomyopathy syndrome (CMS) is a disease associated with severe
      myocarditis primarily in adult farmed Atlantic salmon (Salmo salar L.), caused by
      a double-stranded RNA virus named piscine myocarditis virus (PMCV) with
      structural similarities to the Totiviridae family. Here we present the first
      characterisation of host immune responses to CMS assessed by microarray
      transcriptome profiling. RESULTS: Unvaccinated farmed Atlantic salmon post-smolts
      were infected by intraperitoneal injection of PMCV and developed cardiac
      pathology consistent with CMS. From analysis of heart samples at several time
      points and different tissues at early and clinical stages by oligonucleotide
      microarrays (SIQ2.0 chip), six gene sets representing a broad range of immune
      responses were identified, showing significant temporal and spatial regulation.
      Histopathological examination of cardiac tissue showed myocardial lesions from 6
      weeks post infection (wpi) that peaked at 8-9 wpi and was followed by a recovery.
      Viral RNA was detected in all organs from 4 wpi suggesting a broad tissue
      tropism. High correlation between viral load and cardiac histopathology score
      suggested that cytopathic effect of infection was a major determinant of the
      myocardial changes. Strong and systemic induction of antiviral and IFN-dependent
      genes from 2 wpi that levelled off during infection, was followed by a biphasic
      activation of pathways for B cells and MHC antigen presentation, both peaking at
      clinical pathology. This was preceded by a distinct cardiac activation of
      complement at 6 wpi, suggesting a complement-dependent activation of humoral Ab
      responses. Peak of cardiac pathology and viral load coincided with cardiac
      specific upregulation of T cell response genes and splenic induction of
      complement genes. Preceding the reduction in viral load and pathology, these
      responses were probably important for viral clearance and recovery. CONCLUSIONS:
      By comparative analysis of gene expression, histology and viral load, the
      temporal and spatial regulation of immune responses were characterised and novel
      immune genes identified, ultimately leading to a more complete understanding of
      host-virus responses and pathology and protection in Atlantic salmon during CMS.

PMID- 21943290
TI  - On the lookout for precursor lesions: where does dry skin end and slight hand
      eczema begin?
AB  - BACKGROUND: The prognosis of occupational hand eczema is strongly associated with
      its duration, severity, and the onset of treatment. OBJECTIVES: The study was
      aimed at characterizing skin eruptions that might be potential precursors of
      occupational hand eczema, their pattern, and typical sites in a population at
      moderate risk of hand eczema. PATIENTS/MATERIALS/METHODS: Eight hundred German
      male metal workers took part in a structured interview focused on their medical
      history combined with a dermatological examination of their hands, by use of the
      quantitative Hand Eczema Score for Occupational Screenings, with follow-up 1 year
      later. RESULTS: The most frequent lesions were erythema (91.8%), lichenification
      (98.8%), crusting (70%), and scaling (35%); all other lesions were relatively
      rare (15%). The distribution of lesions remained stable between baseline and
      follow-up. The areas most affected were knuckles, palms, and finger shafts
      (excluding tips). Interdigital regions were uncommonly affected in this sample.
      CONCLUSIONS: Erythema, lichenification, and crusting, indicating constant skin
      'strain', can be regarded as precursor lesions for slight hand eczema, and should
      be monitored quantitatively. As other occupations, for example hairdressing, have
      different predilection sites, it can be concluded that the pattern of
      occupational hand eczema is strongly influenced by the distinct strain profile of
      an occupation.

PMID- 21943291
TI  - Serum uri acid: neuroprotection in thrombolysis. The Bergen NORSTROKE study.
AB  - BACKGROUND: A possible synergic role of serum uric acid (SUA) with thrombolytic
      therapies is controversial and needs further investigations. We therefore
      evaluated association of admission SUA with clinical improvement and clinical
      outcome in patients receiving rt-PA, early admitted patients not receiving rt-PA,
      and patients admitted after time window for rt-PA. METHODS: SUA levels were
      obtained at admission and categorized as low, middle and high, based on 33
      degrees  and 66 degrees  percentile values. Patients were categorized as patients
      admitted within 3 hours of symptom onset receiving rt-PA (rt-PA group), patients
      admitted within 3 hours of symptom onset not receiving rt-PA (non-rt-PA group),
      and patients admitted after time window for rt-PA (late group). Short-term
      clinical improvement was defined as the difference between NIHSS on admission
      minus NIHSS day 7. Favorable outcome was defined as mRS 0 - 3 and unfavorable
      outcome as mRS 4 - 6. RESULTS: SUA measurements were available in 1136 patients.
      Clinical improvement was significantly higher in patients with high SUA levels at
      admission. After adjustment for possible confounders, SUA level showed a positive
      correlation with clinical improvement (r = 0.012, 95% CI 0.002-0.022, p = 0.02)
      and was an independent predictor for favorable stroke outcome (OR 1.004; 95% CI
      1.0002-1.009; p = 0.04) only in the rt-PA group. CONCLUSIONS: SUA may not be
      neuroprotective alone, but may provide a beneficial effect in patients receiving
      thrombolysis.

PMID- 21943292
TI  - EnzymeDetector: an integrated enzyme function prediction tool and database.
AB  - BACKGROUND: The ability to accurately predict enzymatic functions is an essential
      prerequisite for the interpretation of cellular functions, and the reconstruction
      and analysis of metabolic models. Several biological databases exist that provide
      such information. However, in many cases these databases provide partly different
      and inconsistent genome annotations. DESCRIPTION: We analysed nine prokaryotic
      genomes and found about 70% inconsistencies in the enzyme predictions of the main
      annotation resources. Therefore, we implemented the annotation pipeline
      EnzymeDetector. This tool automatically compares and evaluates the assigned
      enzyme functions from the main annotation databases and supplements them with its
      own function prediction. This is based on a sequence similarity analysis, on
      manually created organism-specific enzyme information from BRENDA (Braunschweig
      Enzyme Database), and on sequence pattern searches. CONCLUSIONS: EnzymeDetector
      provides a fast and comprehensive overview of the available enzyme function
      annotations for a genome of interest. The web interface allows the user to work
      with customisable weighting schemes and cut-offs for the different prediction
      methods. These customised quality criteria can easily be applied, and the
      resulting annotation can be downloaded. The summarised view of all used
      annotation sources provides up-to-date information. Annotation errors that occur
      in only one of the databases can be recognised (because of their low relevance
      score). The results are stored in a database and can be accessed at
      http://enzymedetector.tu-bs.de.

PMID- 21943293
TI  - Using emergency department-based inception cohorts to determine genetic
      characteristics associated with long term patient outcomes after motor vehicle
      collision: methodology of the CRASH study.
AB  - BACKGROUND: Persistent musculoskeletal pain and psychological sequelae following
      minor motor vehicle collision (MVC) are common problems with a large economic
      cost. Prospective studies of pain following MVC have demonstrated that
      demographic characteristics, including female gender and low education level, and
      psychological characteristics, including high pre-collision anxiety, are
      independent predictors of persistent pain. These results have contributed to the
      psychological and social components of a biopsychosocial model of post-MVC pain
      pathogenesis, but the biological contributors to the model remain poorly defined.
      Recent experimental studies indicate that genetic variations in adrenergic system
      function influence the vulnerability to post-traumatic pain, but no studies have
      examined the contribution of genetic factors to existing predictive models of
      vulnerability to persistent pain. METHODS/DESIGN: The Project CRASH study is a
      federally supported, multicenter, prospective study designed to determine whether
      variations in genes affecting synaptic catecholamine levels and alpha and beta
      adrenergic receptor function augment social and psychological factors in a
      predictive model of persistent musculoskeletal pain and posttraumatic stress
      disorder (PTSD) following minor MVC. The Project CRASH study will assess pain,
      pain interference and PTSD symptoms at 6 weeks, 6 months, and 1 year in
      approximately 1,000 patients enrolled from 8 Emergency Departments in four states
      with no-fault accident laws. DISCUSSION: The results from this study will provide
      insights into the pathophysiology of persistent pain and PTSD following MVC and
      may serve to improve the ability of clinicians and researchers to identify
      individuals at high risk for adverse outcomes following minor MVC.

PMID- 21943294
TI  - Snow control - an RCT protocol for a web-based self-help therapy to reduce
      cocaine consumption in problematic cocaine users.
AB  - BACKGROUND: Cocaine use has increased in most European countries, including
      Switzerland, and many states worldwide. The international literature has
      described treatment models that target the general population. In addition to
      supplying informative measures at the level of primary and secondary prevention,
      the literature also offers web-based self-help tools for problematic substance
      users, which is in line with tertiary prevention. Such programs, however, have
      been primarily tested on individuals with problematic alcohol and cannabis
      consumption, but not on cocaine-dependent individuals. METHODS/DESIGN: This paper
      presents the protocol of a randomised clinical trial to test the effectiveness of
      a web-based self-help therapy to reduce cocaine use in problematic cocaine users.
      The primary outcome is severity of cocaine dependence. Secondary outcome measures
      include cocaine craving, consumption of cocaine and other substances of abuse in
      the past month, and changes in depression characteristics. The therapy group will
      receive a 6-week self-help therapy to reduce cocaine consumption based on methods
      of Cognitive Behavioural Therapy, principles of Motivational Interviewing and
      self-control practices. The control group will be presented weekly psycho
      educative information with a quiz. The predictive validity of participant
      characteristics on treatment retention and outcome will be explored. DISCUSSION:
      To the best of our knowledge, this will be the first randomised clinical trial to
      test the effectiveness of online self-help therapy to reduce or abstain from
      cocaine use. It will also investigate predictors of outcome and retention. This
      trial is registered at Current Controlled Trials and is traceable as NTR
      ISRCTN93702927.

PMID- 21943295
TI  - Key challenges in simulated patient programs: an international comparative case
      study.
AB  - BACKGROUND: The literature on simulated or standardized patient (SP) methodology
      is expanding. However, at the level of the program, there are several gaps in the
      literature. We seek to fill this gap through documenting experiences from four
      programs in Australia, Canada, Switzerland and the United Kingdom. We focused on
      challenges in SP methodology, faculty, organisational structure and quality
      assurance. METHODS: We used a multiple case study method with cross-case
      synthesis. Over eighteen months during a series of informal and formal
      interactions (focused meetings and conference presentations) we documented key
      characteristics of programs and drew on secondary document sources. RESULTS:
      Although programs shared challenges in SP methodology they also experienced
      differences. Key challenges common to programs included systematic quality
      assurance and the opportunity for research. There were differences in the
      terminology used to describe SPs, in their recruitment and training. Other
      differences reflected local conditions and demands in organisational structure,
      funding relationships with the host institution and national trends, especially
      in assessments. CONCLUSION: This international case study reveals similarities
      and differences in SP methodology. Programs were highly contextualised and have
      emerged in response to local, institutional, profession/discipline and national
      conditions. Broader trends in healthcare education have also influenced
      development. Each of the programs experienced challenges in the same themes but
      the nature of the challenges often varied widely.

PMID- 21943296
TI  - Time to focus on outcome assessment tools for childhood vasculitis.
AB  - Childhood systemic vasculitides are a group of rare diseases with multi-organ
      involvement and potentially devastating consequences. After establishment of new
      classification criteria (Ankara consensus conference in 2008), it is now time to
      establish measures for proper definition of activity and damage in childhood
      primary vasculitis. By comparison to adult vasculitis, there is no consensus for
      indices of activity and damage assessment in childhood vasculitis. Assessment of
      disease activity is likely to become a major area of interest in pediatric
      rheumatology in the near future. After defining the classification criteria for
      primary systemic childhood vasculitis, the next step was to perform a validation
      study using the original Birmingham vasculitis activity score as well as the
      disease extent index to measure disease activity in childhood vasculitis.
      Presently, there are efforts in place to develop a pediatric vasculitis activity
      score. This paper reviews the current understanding about the assessment tools
      (i.e., clinical features, laboratory tests, radiologic assessments, etc.) widely
      used for evaluation of the disease activity and damage status of the children
      with vasculitis.

PMID- 21943298
TI  - Health information: diffusing information to knowledge and action.

PMID- 21943297
TI  - Drinking carrot juice increases total antioxidant status and decreases lipid
      peroxidation in adults.
AB  - BACKGROUND: High prevalence of obesity and cardiovascular disease is attributable
      to sedentary lifestyle and eating diets high in fat and refined carbohydrate
      while eating diets low in fruit and vegetables. Epidemiological studies have
      confirmed a strong association between eating diets rich in fruits and vegetables
      and cardiovascular health. The aim of this pilot study was to determine whether
      drinking fresh carrot juice influences antioxidant status and cardiovascular risk
      markers in subjects not modifying their eating habits. METHODS: An experiment was
      conducted to evaluate the effects of consuming 16 fl oz of daily freshly squeezed
      carrot juice for three months on cardiovascular risk markers, C-reactive protein,
      insulin, leptin, interleukin-1alpha, body fat percentage, body mass index (BMI),
      blood pressure, antioxidant status, and malondialdehyde production. Fasting blood
      samples were collected pre-test and 90 days afterward to conclude the study.
      RESULTS: Drinking carrot juice did not affect (P > 0.1) the plasma cholesterol,
      triglycerides, Apo A, Apo B, LDL, HDL, body fat percentage, insulin, leptin,
      interleukin-1alpha, or C-reactive protein. Drinking carrot juice decreased (P =
      0.06) systolic pressure, but did not influence diastolic pressure. Drinking
      carrot juice significantly (P < 0.05) increased the plasma total antioxidant
      capacity and decreased (P < 0.05) the plasma malondialdehyde production.
      CONCLUSION: Drinking carrot juice may protect the cardiovascular system by
      increasing total antioxidant status and by decreasing lipid peroxidation
      independent of any of the cardiovascular risk markers measured in the study.

PMID- 21943299
TI  - Experimental infection of Bama miniature pigs with a highly virulent classical
      swine fever virus.
AB  - BACKGROUND: Currently, larger domestic pigs are only animals widely used in
      vaccine evaluation and pathogenicity study of classical swine fever virus (CSFV).
      This study was aimed to create an alternative animal experimental infection model
      of CSFV. RESULTS: Twenty specific-pathogen-free Bama miniature pigs were randomly
      divided into two groups and rooms, infected and non-infected, and the pigs in the
      infected group were inoculated intramuscularly with 104, 105 or 106 TCID50
      (median tissue culture infective dose) CSFV Shimen strain (n = 5 * 3) or left
      uninoculated to serve as in-contact pigs (n = 3). The uninfected control pigs (n
      = 2) were housed in a separate room. Clinical signs, body temperature, viraemia,
      tissue antigen distribution, pathological changes and seroconversion were
      monitored. Clinical signs were observed as early as 2 days post-inoculation (dpi)
      in all infected pigs (though mild in contact pigs), but not non-infected control
      pigs. All inoculated pigs showed viraemia by 6 dpi. The in-contact pigs showed
      lower levels of viraemia. At 10 dpi, seroconversion was noted in five of the 15
      inoculated pigs. All inoculated or one in-contact pigs died by 15 dpi.
      CONCLUSIONS: These results show that Bama miniature pigs support productive CSFV
      infection and display clinical signs and pathological changes consistent with
      CSFV infections observed in larger domestic pigs.

PMID- 21943300
TI  - Evaluation of triblock copolymeric micelles of delta- valerolactone and poly
      (ethylene glycol) as a competent vector for doxorubicin delivery against cancer.
AB  - BACKGROUND: Specific properties of amphiphilic copolymeric micelles like small
      size, stability, biodegradability and prolonged biodistribution have projected
      them as promising vectors for drug delivery. To evaluate the potential of delta
      valerolactone based micelles as carriers for drug delivery, a novel triblock
      amphiphilic copolymer poly(delta-valerolactone)/poly(ethylene glycol)/poly(delta
      valerolactone) (VEV) was synthesized and characterized using IR, NMR, GPC, DTA
      and TGA. To evaluate VEV as a carrier for drug delivery, doxorubicin (DOX)
      entrapped VEV micelles (VEVDMs) were prepared and analyzed for in vitro antitumor
      activity. RESULTS: VEV copolymer was successfully synthesized by ring opening
      polymerization and the stable core shell structure of VEV micelles with a low
      critical micelle concentration was confirmed by proton NMR and fluorescence based
      method. Doxorubicin entrapped micelles (VEVDMs) prepared using a modified single
      emulsion method were obtained with a mean diameter of 90 nm and high
      encapsulation efficiency showing a pH dependent sustained doxorubicin release.
      Biological evaluation in breast adenocarcinoma (MCF7) and glioblastoma (U87MG)
      cells by flow cytometry showed 2-3 folds increase in cellular uptake of VEVDMs
      than free DOX. Block copolymer micelles without DOX were non cytotoxic in both
      the cell lines. As evaluated by the IC50 values VEVDMs induced 77.8, 71.2, 81.2%
      more cytotoxicity in MCF7 cells and 40.8, 72.6, 76% more cytotoxicity in U87MG
      cells than pristine DOX after 24, 48, 72 h treatment, respectively. Moreover,
      VEVDMs induced enhanced apoptosis than free DOX as indicated by higher shift in
      Annexin V-FITC fluorescence and better intensity of cleaved PARP. Even though,
      further studies are required to prove the efficacy of this formulation in vivo
      the comparable G2/M phase arrest induced by VEVDMs at half the concentration of
      free DOX confirmed the better antitumor efficacy of VEVDMs in vitro. CONCLUSIONS:
      Our studies clearly indicate that VEVDMs possess great therapeutic potential for
      long-term tumor suppression. Furthermore, our results launch VEV as a promising
      nanocarrier for an effective controlled drug delivery in cancer chemotherapy.

PMID- 21943302
TI  - External validation of models for predicting pneumonia after cardiac surgery.
AB  - BACKGROUND: Approximately 20% of patients become infected after cardiac surgery.
      Pneumonia is one of the most serious infections, increasing the chance of death
      14-fold. The higher frequency of pneumonia after cardiac surgery may be explained
      by surgical conditions. Focusing on high-risk groups may make several strategies
      more effective, and external validation is an essential phase of building
      prediction models to identify such groups. PURPOSE: To compare the performance of
      two previously validated prediction models for pneumonia after cardiac surgery
      (classification and regression tree [CART] and a logistic regression model [LRM])
      on an external validation set. METHODS: A series of 527 adult cardiac surgery
      patients at a small private hospital were analyzed prospectively to identify
      prognostic factors for pneumonia. Pneumonia occurred in 7.6% of patients in this
      derivation set. The probability of pneumonia onset was estimated by means of CART
      and LRM using a cut-off point that maximized both sensitivity and specificity
      without decreasing accuracy greatly. The results were confirmed with a validation
      set obtained by enrollment of consecutive 333 adult patients undergoing major
      cardiac surgery. There were significant differences in the fraction of emergency
      cases in the derivation and validation sets. RESULTS: The LRM selected emergency
      surgery (odds ratio [OR] 5.28), chronic obstructive pulmonary disease (COPD)(OR
      4.29), ventricular dysfunction (OR 2.68), and age (OR 1.04) as independent
      predictors of pneumonia. The CART model selected emergency surgery, age, unstable
      angina, body mass index, COPD, weight, and ventricular dysfunction as predictors.
      The CART model also selected low body mass index, weight, and unstable angina as
      predictors. Emergency surgery was the strongest predictor in both models. The LRM
      performed better than the CART model for the global, discrimination, and
      calibration measures. CONCLUSION: The LRM model displayed superior performance. A
      possible advantage of the CART prediction model is that it may be easier to
      interpret via its graphical presentation than prediction models based on logistic
      regression. However, there are a number of disadvantages of the CART approach.
      The LRM model can be used by infection control practitioners for risk adjustment
      across different periods or units and for evaluation of the efficacy of new
      technologies.

PMID- 21943301
TI  - High prevalence of vitamin D insufficiency and its association with obesity and
      metabolic syndrome among Malay adults in Kuala Lumpur, Malaysia.
AB  - BACKGROUND: Vitamin D status, as indicated by 25-hydroxyvitamin D is inversely
      associated with adiposity, glucose homeostasis, lipid profiles, and blood
      pressure along with its classic role in calcium homeostasis and bone metabolism.
      It is also shown to be inversely associated with metabolic syndrome and
      cardiovascular diseases in western populations. However, evidence from the Asian
      population is limited. Therefore, we aim to study the prevalence of vitamin D
      insufficiency (< 50 nmol/L) and the association of 25-hydroxyvitamin D with
      metabolic risk factors among an existing Malay cohort in Kuala Lumpur. METHODS:
      This is an analytical cross sectional study. A total of 380 subjects were sampled
      and their vitamins D status (25-hydroxyvitamin D), fasting blood glucose, full
      lipid profile were assessed using venous blood. Systolic and diastolic blood
      pressure, weight, height and waist circumference were measured following standard
      protocols. Socio-demographic data such as sex, age, smoking status etc were also
      collected. Data was analysed using t-test, chi-square test, General Linear Model
      and multiple logistic regression. RESULTS: Females made up 58% of the sample. The
      mean age of respondents was 48.5 (SD 5.2) years. Females had significantly lower
      mean Vitamin D levels (36.2; 95% CI: 34.5, 38.0 nmol/L) compared to males (56.2;
      95% CI: 53.2, 59.2 nmol/L). Approximately 41% and 87% of males and females
      respectively had insufficient (< 50 nmol/L) levels of 25-hydroxyvitamin D (p <
      0.001). The prevalence of Metabolic Syndrome for the whole sample was 38.4 (95%
      CI: 33.5, 43.3)%. In the multivariate model (adjusted for age, sex, abdominal
      obesity, HDL-cholesterol, diastolic blood pressure), insufficient Vitamin D
      status was significantly associated with 1-year age increments (OR: 0.93; 95% CI:
      0.88, 0.98), being female (OR: 8.68; 95% CI: 5.08, 14.83) and abdominal obesity
      (OR: 2.57; 95% CI: 1.51, 4.39). Respondents with insufficient vitamin D were
      found to have higher odds of having Metabolic Syndrome (OR: 1.73; 95% CI: 1.02,
      2.92) after adjusting for age and sex. CONCLUSIONS: Our results highlight the
      high prevalence of vitamin D insufficiency among Malay adults in Kuala Lumpur.
      Vitamin D insufficiency is independently associated with younger age, female sex
      and greater abdominal obesity. Vitamin D insufficiency is also associated with
      Metabolic Syndrome.

PMID- 21943303
TI  - Is intensive multimodality therapy the best treatment for fournier gangrene?
      Evaluation of clinical outcome and survival rate of 41 patients.
AB  - BACKGROUND: To evaluate the effect of surgical wound debridement, antibiotics,
      and hyperbaric oxygen (HBO) in the treatment of Fournier gangrene (FG). METHODS:
      Forty-one patients with a mean age of 54.3+/-14.6 years were referred to our
      department with a diagnosis of FG. To calculate a Fourier Gangrene Severity Index
      (FGSI), nine factors were assessed (temperature; heart rate; ventilatory rate;
      serum sodium, potassium, creatinine, and bicarbonate concentrations; hematocrit;
      and leukocyte count). After clinical stabilization, extensive debridement of the
      necrotic tissue was performed, and a surgical vacuum-assisted closure (V.A.C.(r))
      device was applied. Hyperbaric oxygen was administered; medical therapy consisted
      of intravenous antibiotics, electrolyte replacement, and parenteral nutrition.
      RESULTS: Intraoperative cultures revealed Escherichia coli in 27 patients (66%),
      Pseudomonas aeruginosa in 28 (68%), gram-positive cocci in 24 (59%), and mixed
      flora (aerobic and anaerobic bacteria) in 39 (95%). One month after primary
      debridement, wound granulation was sufficient for plastic surgical reconstruction
      in all patients. CONCLUSION: Because of the rapid worsening of FG, early
      diagnosis and immediate, aggressive multi-modality therapy with surgical
      debridement and broad-spectrum empiric antibiotics is crucial. The utility of HBO
      remains unproved.

PMID- 21943304
TI  - Challenges and barriers to improving care of the musculoskeletal patient of the
      future - a debate article and global perspective.
AB  - BACKGROUND: With greater technological developments in the care of
      musculoskeletal patients, we are entering an era of rapid change in our
      understanding of the pathophysiology of traumatic injury; assessment and
      treatment of polytrauma and related disorders; and treatment outcomes. In
      developed countries, it is very likely that we will have algorithms for the
      approach to many musculoskeletal disorders as we strive for the best approach
      with which to evaluate treatment success. This debate article is founded on
      predictions of future health care needs that are solely based on the subjective
      inputs and opinions of the world's leading orthopedic surgeons.Hence, it
      functions more as a forum-based rather than a scientific-based presentation. This
      expose was designed to stimulate debate about the emerging patients' needs in the
      future predicted by leading orthopedic surgeons that provide some hint as to the
      right direction for orthopedic care and outlines the important topics in this
      area. DISCUSSION: The authors aim to provide a general overview of orthopedic
      care in a typical developed country setting. However, the regional diversity of
      the United States and every other industrialized nation should be considered as a
      cofactor that may vary to some extent from our vision of improved orthopedic and
      trauma care of the musculoskeletal patient on an interregional level.In this
      forum, we will define the current and future barriers in developed countries
      related to musculoskeletal trauma, total joint arthroplasty, patient safety and
      injuries related to military conflicts, all problems that will only increase as
      populations age, become more mobile, and deal with political crisis. SUMMARY: It
      is very likely that the future will bring a more biological approach to fracture
      care with less invasive surgical procedures, flexible implants, and more rapid
      rehabilitation methods. This international consortium challenges the trauma and
      implants community to develop outcome registries that are managed through health
      care offices and to prepare effectively for the many future challenges that lie
      in store for those who treat musculoskeletal conditions.

PMID- 21943305
TI  - Detecting autozygosity through runs of homozygosity: a comparison of three
      autozygosity detection algorithms.
AB  - BACKGROUND: A central aim for studying runs of homozygosity (ROHs) in genome-wide
      SNP data is to detect the effects of autozygosity (stretches of the two
      homologous chromosomes within the same individual that are identical by descent)
      on phenotypes. However, it is unknown which current ROH detection program, and
      which set of parameters within a given program, is optimal for differentiating
      ROHs that are truly autozygous from ROHs that are homozygous at the marker level
      but vary at unmeasured variants between the markers. METHOD: We simulated 120 Mb
      of sequence data in order to know the true state of autozygosity. We then
      extracted common variants from this sequence to mimic the properties of SNP
      platforms and performed ROH analyses using three popular ROH detection programs,
      PLINK, GERMLINE, and BEAGLE. We varied detection thresholds for each program
      (e.g., prior probabilities, lengths of ROHs) to understand their effects on
      detecting known autozygosity. RESULTS: Within the optimal thresholds for each
      program, PLINK outperformed GERMLINE and BEAGLE in detecting autozygosity from
      distant common ancestors. PLINK's sliding window algorithm worked best when using
      SNP data pruned for linkage disequilibrium (LD). CONCLUSION: Our results provide
      both general and specific recommendations for maximizing autozygosity detection
      in genome-wide SNP data, and should apply equally well to research on whole
      genome autozygosity burden or to research on whether specific autozygous regions
      are predictive using association mapping methods.

PMID- 21943307
TI  - Phosphorylation of collapsin response mediator protein-2 disrupts neuronal
      maturation in a model of adult neurogenesis: Implications for neurodegenerative
      disorders.
AB  - BACKGROUND: Recent studies suggest that the pathogenic process in
      neurodegenerative disorders may disrupt mature neuronal circuitries and
      neurogenesis in the adult brain. Abnormal activation of CDK5 is associated with
      neurodegenerative disorders, and recently a critical role for CDK5 in adult
      neurogenesis has been identified. We have developed an in vitro model of abnormal
      CDK5 activation during adult hippocampal neurogenesis, and here we used this
      model to investigate aberrantly phosphorylated downstream targets of CDK5.
      RESULTS: Abnormal CDK5 activation in an in vitro model of adult neurogenesis
      results in hyperphosphorylation of collapsin-response mediator protein-2 (CRMP2)
      and impaired neurite outgrowth. Inhibition of CDK5, or expression of a non
      phosphorylatable (S522A) CRMP2 construct reduced CRMP2 hyperphosphorylation, and
      reversed neurite outgrowth deficits. CRMP2 plays a role in microtubule dynamics;
      therefore we examined the integrity of microtubules in this model using
      biochemical and electron microscopy techniques. We found that microtubule
      organization was disrupted under conditions of CDK5 activation. Finally, to study
      the relevance of these findings to neurogenesis in neurodegenerative conditions
      associated with HIV infection, we performed immunochemical analyses of the brains
      of patients with HIV and transgenic mice expressing HIV-gp120 protein. CDK5
      mediated CRMP2 phosphorylation was significantly increased in the hippocampus of
      patients with HIV encephalitis and in gp120 transgenic mice, and this effect was
      rescued by genetic down-modulation of CDK5 in the mouse model. CONCLUSIONS: These
      results reveal a functional mechanism involving microtubule destabilization
      through which abnormal CDK5 activation and CRMP2 hyperphosphorylation might
      contribute to defective neurogenesis in neurodegenerative disorders such as HIV
      encephalitis.

PMID- 21943306
TI  - Habitually exercising older men do not demonstrate age-associated vascular
      endothelial oxidative stress.
AB  - We tested the hypothesis that older men who perform habitual aerobic exercise do
      not demonstrate age-associated vascular endothelial oxidative stress compared
      with their sedentary peers. Older exercising men (n=13, 62+/-2 years) had higher
      (P<0.05) physical activity (79+/-7 vs. 30+/-6 MET hours per week) and maximal
      exercise oxygen consumption (42+/-1 vs. 29+/-1 mL kg(-1) per minute) vs.
      sedentary men (n=28, 63+/-1 years). Brachial artery flow-mediated dilation (FMD),
      a measure of vascular endothelial function, was greater (P<0.05) in the
      exercising vs. sedentary older men (6.3+/-0.5 vs. 4.9+/-0.4%Delta) and not
      different than young controls (n=20, 25+/-1 years, 7.1+/-0.5%Delta). In vascular
      endothelial cells sampled from the brachial artery, nitrotyrosine, a marker of
      oxidative stress, was 51% lower in the exercising vs. sedentary older men (0.38+/
      0.06 vs. 0.77+/-0.10 AU). This was associated with lower endothelial expression
      of the oxidant enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase
      (p47(phox) subunit, 0.33+/-0.05 vs. 0.61+/-0.09 AU) and the redox-sensitive
      transcription factor nuclear factor kappa B (NFkappaB) (p65 subunit, 0.36+/-0.05
      vs. 0.72+/-0.09 AU). Expression of the antioxidant enzyme manganese superoxide
      dismutase (SOD) (0.57+/-0.13 vs. 0.30+/-0.04 AU) and activity of endothelium
      bound extracellular SOD were greater (6.4+/-0.5 vs. 5.0+/-0.6 U mL(-1) per
      minute) in the exercising men (both P<0.05), but differences no longer were
      significant after correcting for adiposity and circulating metabolic factors.
      Overall, values for the young controls differed with those for the sedentary, but
      not the exercising older men. Older men who exercise regularly do not demonstrate
      vascular endothelial oxidative stress, and this may be a key molecular mechanism
      underlying their reduced risk of cardiovascular diseases.

PMID- 21943308
TI  - Effect of using HIV and infant feeding counselling cards on the quality of
      counselling provided to HIV positive mothers: a cluster randomized controlled
      trial.
AB  - BACKGROUND: Counselling human immunodeficiency virus (HIV) positive mothers on
      safer infant and young child feeding (IYCF) options is an important component of
      programmes to prevent mother to child transmission of HIV, but the quality of
      counselling is often inadequate. The aim of this study was to determine the
      effect the World Health Organization HIV and infant feeding cards on the quality
      of counselling provided to HIV positive mothers by health workers about safer
      infant feeding options. METHOD: This was a un-blinded cluster-randomized
      controlled field trial in which 36 primary health facilities in Kafue and Lusaka
      districts in Zambia were randomized to intervention (IYCF counselling with
      counselling cards) or non- intervention arm (IYCF counselling without counselling
      cards). Counselling sessions with 10 HIV positive women attending each facility
      were observed and exit interviews were conducted by research assistants. RESULTS:
      Totals of 180 women in the intervention group and 180 women in the control group
      were attended to by health care providers and interviewed upon exiting the health
      facility. The health care providers in the intervention facilities more often
      discussed the advantages of disclosing their HIV status to a household member (RR
      = 1.46, 95% CI [1.11, 1.92]); used visual aids in explaining the risk of HIV
      transmission through breast milk (RR = 4.65, 95% CI [2.28, 9.46]); and discussed
      the advantages and disadvantages of infant feeding options for HIV positive
      mothers (all p values < 0.05). The differences also included exploration of the
      home situation (p < 0.05); involving the partner in the process of choosing a
      feeding option (RR = 1.38, 95% CI [1.09, 1.75]); and exploring how the mother
      will manage to feed the baby when she is at work (RR = 2.82, 95% CI [1.70,
      4.67]). The clients in the intervention group felt that the provider was more
      caring and understanding (RR = 1.81, 95% CI [1.19, 2.75]). CONCLUSION: The
      addition of counselling cards to the IYCF counselling session for HIV positive
      mothers were a valuable aid to counselling and significantly improved the quality
      of the counselling session.

PMID- 21943309
TI  - Clinical features of headache associated with mobile phone use: a cross-sectional
      study in university students.
AB  - BACKGROUND: Headache has been reported to be associated with mobile phone (MP)
      use in some individuals. The causal relationship between headache associated with
      MP use (HAMP) and MP use is currently undetermined. Identifying the clinical
      features of HAMP may help in clarifying the pathophysiology of HAMP and in
      managing symptoms of individuals with HAMP. The aim of the present study is to
      describe the clinical features of HAMP. METHODS: A 14-item questionnaire
      investigating MP use and headache was administered to 247 medical students at
      Hallym University, Korea. Individual telephone interviews were subsequently
      conducted with those participants who reported HAMP more than 10 times during the
      last 1 year on the clinical features of HAMP. We defined HAMP as a headache
      attack during MP use or within 1 hour after MP use. RESULTS: In total, 214
      (86.6%) students completed and returned the questionnaire. Forty (18.9%) students
      experienced HAMP more than 10 times during the last 1 year in the questionnaire
      survey. In subsequent telephone interviews, 37 (97.4%) interviewed participants
      reported that HAMP was triggered by prolonged MP use. HAMP was usually dull or
      pressing in quality (30 of 38, 79.0%), localised ipsilateral to the side of MP
      use (32 of 38, 84.2%), and associated with a burning sensation (24 of 38, 63.2%).
      CONCLUSION: We found that HAMP usually showed stereotyped clinical features
      including mild intensity, a dull or pressing quality, localisation ipsilateral to
      the side of MP use, provocation by prolonged MP use and often accompanied by a
      burning sensation.

PMID- 21943310
TI  - General practitioner characteristics and delay in cancer diagnosis. a population
      based cohort study.
AB  - BACKGROUND: Delay in cancer diagnosis may have serious prognostic consequences,
      and some patients experience delays lasting several months. However, we have no
      knowledge whether such delays are associated with general practitioner (GP)
      characteristics. The aim of the present study was to analyse whether GP and
      practice characteristics are associated with the length of delay in cancer
      diagnosis. METHODS: The study was designed as a population-based cohort study.
      The setting was the County of Aarhus, Denmark (640,000 inhabitants). Participants
      include 334 GPs and their 1,525 consecutive, newly diagnosed cancer patients.
      During one year (September 2004 to August 2005), patients with incident cancer
      were enrolled from administrative registries. GPs completed questionnaires on the
      patients' diagnostic pathways and on GP and practice characteristics. Delay was
      categorised as patient-related (more than 60 days), doctor-related (more than 30
      days) and system-related (more than 90 days). The associations between delay and
      characteristics were assessed in a logistic regression model using odds ratios
      (ORs). RESULTS: No GP characteristics (seniority, practice organization, list
      size, participation in continuing medical education, job satisfaction and level
      of burnout) were associated with doctor delay. Patients of female GPs more often
      had a short patient delay than patients of male GPs (OR 0.44, 95% confidence
      interval (95% CI) 0.28 to 0.71). Patients whose GPs provided many services (OR
      0.66, 95% CI 0.44 to 0.95) and patients attending GPs with little former
      knowledge of their patients (OR 0.68, 95% CI 0.47 to 0.99) more often experienced
      a short system delay than patients attending GPs with less activity and more
      knowledge of their patients. Patients listed with a female GP more often
      experienced a long system delay than patients of male GPs (OR 1.50, 95% CI 1.02
      to 2.21). Finally, patients with low GP-reported compliance more often
      experienced a long system delay (OR 1.73, 95% CI 1.07 to 2.80) than patients with
      higher compliance. CONCLUSIONS: GP characteristics were not statistically
      significantly associated with doctor delay. However, some GP characteristics were
      associated with patient and system delay, which indicates that these factors may
      be important for understanding patient delay (e.g. perceived GP accessibility and
      the GP-patient relationship) and system delay (e.g. the GP's experience and
      opportunities for referring and coordinating diagnostic work-up).

PMID- 21943311
TI  - Posttranslational modification of Argonautes and their role in small RNA-mediated
      gene regulation.
AB  - Shortly after their discovery, repertoires of miRNA were identified, together
      with proteins involved in their biogenesis and action. It is now obvious that
      miRNA-mediated gene regulation itself is regulated at multiple levels.
      Identifying the regulatory mechanisms that underpin small RNA homeostasis by
      modulation of their biogenesis and action has become a key issue, which can be
      partly resolved by identifying mediators of Argonautes turnover. An emerging
      theme in the control of Argonaute stability and activity is through
      posttranslational modifications, which are the focus of this review.

PMID- 21943312
TI  - Dietary sources of animal and plant protein intake among Flemish preschool
      children and the association with socio-economic and lifestyle-related factors.
AB  - BACKGROUND: The aims of this study were to assess the intake of animal, plant and
      food group-specific protein, and to investigate their associations with socio
      economic and lifestyle-related factors in Flemish preschoolers. METHODS: Three
      day estimated dietary records were collected from 661 preschoolers aged 2.5-6.5 y
      (338 boys and 323 girls). Multiple linear regression analysis was used to
      investigate the association between animal, plant, and food group-specific
      protein intake and socio-economic and lifestyle factors. RESULTS: Animal proteins
      (mean 38 g/d) were the main source of total protein (mean 56 g/d), while mean
      plant protein intake amounted to 18 g/d. The group of meat, poultry, fish and
      eggs was the main contributor (51%) to animal protein intake, followed by milk
      and milk products (35%). Bread and cereals (41%) contributed most to the plant
      protein intake, followed by low-nutritious, energy-dense foods (21%). With higher
      educated fathers and mothers as reference, respectively, preschoolers with lower
      secondary and secondary paternal education had lower animal, dairy-, and meat
      derived protein intakes, and those with lower secondary and secondary maternal
      education consumed less plant, and bread and cereal-derived proteins. Compared to
      children with high physical activity levels, preschoolers with low and moderate
      physical activity had lower animal and plant protein intakes. Significantly
      higher potatoes and grains-, and fish- derived proteins were reported for
      children of smoking mothers and fathers, respectively, compared to those of non
      smoking mothers and fathers. CONCLUSIONS: The total protein intake of Flemish
      preschoolers was sufficient according to the recommendations of the Belgian
      Superior Health Council. Parental level of education and smoking status might
      play a role in the sources of children's dietary proteins.

PMID- 21943313
TI  - Analysing the operative experience of basic surgical trainees in Ireland using a
      web-based logbook.
AB  - BACKGROUND: There is concern about the adequacy of operative exposure in surgical
      training programmes, in the context of changing work practices. We aimed to
      quantify the operative exposure of all trainees on the National Basic Surgical
      Training (BST) programme in Ireland and compare the results with arbitrary
      training targets. METHODS: Retrospective analysis of data obtained from a web
      based logbook (http://www.elogbook.org) for all general surgery and orthopaedic
      training posts between July 2007 and June 2009. RESULTS: 104 trainees recorded
      23,918 operations between two 6-month general surgery posts. The most common
      general surgery operation performed was simple skin excision with trainees
      performing an average of 19.7 (+/- 9.9) over the 2-year training programme.
      Trainees most frequently assisted with cholecystectomy with an average of 16.0
      (+/- 11.0) per trainee. Comparison of trainee operative experience to arbitrary
      training targets found that 2-38% of trainees achieved the targets for 9
      emergency index operations and 24-90% of trainees achieved the targets for 8
      index elective operations. 72 trainees also completed a 6-month post in
      orthopaedics and recorded 7,551 operations. The most common orthopaedic operation
      that trainees performed was removal of metal, with an average of 2.90 (+/- 3.27)
      per trainee. The most common orthopaedic operation that trainees assisted with
      was total hip replacement, with an average of 10.46 (+/- 6.21) per trainee.
      CONCLUSIONS: A centralised web-based logbook provides valuable data to analyse
      training programme performance. Analysis of logbooks raises concerns about
      operative experience at junior trainee level. The provision of adequate operative
      exposure for trainees should be a key performance indicator for training
      programmes.

PMID- 21943314
TI  - Reduced cytotoxicity of insulin-immobilized CdS quantum dots using PEG as a
      spacer.
AB  - Cytotoxicity is a severe problem for cadmium sulfide nanoparticles (CSNPs) in
      biological systems. In this study, mercaptoacetic acid-coated CSNPs, typical
      semiconductor Q-dots, were synthesized in aqueous medium by the arrested
      precipitation method. Then, amino-terminated polyethylene glycol (PEG) was
      conjugated to the surface of CSNPs (PCSNPs) in order to introduce amino groups to
      the surface. Finally, insulin was immobilized on the surface of PCSNPs (ICSNPs)
      to reduce cytotoxicity as well as to enhance cell compatibility. The presence of
      insulin on the surface of ICSNPs was confirmed by observing infrared absorptions
      of amide I and II. The mean diameter of ICSNPs as determined by dynamic light
      scattering was about 38 nm. Human fibroblasts were cultured in the absence and
      presence of cadmium sulfide nanoparticles to evaluate cytotoxicity and cell
      compatibility. The results showed that the cytotoxicity of insulin-immobilized
      cadmium sulfide nanoparticles was significantly suppressed by usage of PEG as a
      spacer. In addition, cell proliferation was highly facilitated by the addition of
      ICSNPs. The ICSNPs used in this study will be potentials to be used in bio
      imaging applications.

PMID- 21943316
TI  - A comparative study on gene-set analysis methods for assessing differential
      expression associated with the survival phenotype.
AB  - BACKGROUND: Many gene-set analysis methods have been previously proposed and
      compared through simulation studies and analysis of real datasets for binary
      phenotypes. We focused on the survival phenotype and compared the performances of
      Gene Set Enrichment Analysis (GSEA), Global Test (GT), Wald-type Test (WT) and
      Global Boost Test (GBST) methods in a simulation study and on two ovarian cancer
      data sets. We considered two versions of GSEA by allowing different weights:
      GSEA1 uses equal weights, yielding results similar to the Kolmogorov-Smirnov
      test; while GSEA2's weights are based on the correlation between genes and the
      phenotype. RESULTS: We compared GSEA1, GSEA2, GT, WT and GBST in a simulation
      study with various settings for the correlation structure of the genes and the
      association parameter between the survival outcome and the genes. Simulation
      results indicated that GT, WT and GBST consistently have higher power than GSEA1
      and GSEA2 across all scenarios. However, the power of the five tests depends on
      the combination of correlation structure and association parameter. For the
      ovarian cancer data set, using the FDR threshold of q < 0.1, the GT, WT and GBST
      detected 12, 6 and 8 significant pathways, respectively, whereas neither GSEA1
      nor GSEA2 detected any significant pathways. In addition, among the pathways
      found significant by GT, WT, and GBST, three pathways--Purine metabolism,
      Leukocyte transendothelial migration and Jak-STAT signaling pathway--overlapped
      with those reported in previous ovarian cancer microarray studies. CONCLUSION:
      Simulation studies and a real data example indicate that GT, WT and GBST tend to
      have high power, whereas GSEA1 and GSEA2 have lower power. We also found that the
      power of the five tests is much higher when genes are correlated than when genes
      are independent, when survival is positively associated with genes. It seems that
      there is a synergistic effect in detecting significant gene sets when significant
      genes have within-class correlation and the association between survival and
      genes is positive or negative (i.e., one-direction correlation).

PMID- 21943315
TI  - A study of the effectiveness of telepsychiatry-based culturally sensitive
      collaborative treatment of depressed Chinese Americans.
AB  - BACKGROUND: Chinese American patients with Major Depressive Disorder (MDD) tend
      to underutilize mental health services and are more likely to seek help in
      primary care settings than from mental health specialists. Our team has reported
      that Culturally Sensitive Collaborative Treatment (CSCT) is effective in
      improving recognition and treatment engagement of depressed Chinese Americans in
      primary care. The current study builds on this prior research by incorporating
      telemedicine technology into the CSCT model. METHODS/DESIGN: We propose a
      randomized controlled trial to evaluate the acceptability and effectiveness of a
      telepsychiatry-based culturally sensitive collaborative treatment (T-CSCT)
      intervention targeted toward Chinese Americans. Patients meeting the study's
      eligibility criteria will receive either treatment as usual or the intervention
      under investigation. The six-month intervention involves: 1) an initial
      psychiatric interview using a culturally sensitive protocol via videoconference;
      2) eight scheduled phone visits with a care manager assigned to the patient, who
      will monitor the patient's progress, as well as medication side effects and
      dosage if applicable; and 3) collaboration between the patient's PCP,
      psychiatrist, and care manager. Outcome measures include depressive symptom
      severity as well as patient and PCP satisfaction with the telepsychiatry-based
      care management service. DISCUSSION: The study investigates the T-CSCT model,
      which we believe will increase the feasibility and practicality of the CSCT model
      by adopting telemedicine technology. We anticipate that this model will expand
      access to culturally competent psychiatrists fluent in patients' native languages
      to improve treatment of depressed minority patients in primary care settings.
      TRIAL REGISTRATION: NCT00854542.

PMID- 21943317
TI  - Effect of genistein on the activities of cytochrome P450 3A and P-glycoprotein in
      Chinese healthy participants.
AB  - To determine the effect of genistein on cytochrome P450 3A (CYP3A) and P
      glycoprotein (P-gp) function using the probe substrates midazolam and talinolol,
      respectively. Eighteen healthy adult male participants were enrolled in a two
      phase randomized crossover design. In each phase, the participants received
      placebo or genistein for 14 days. On the 15th day, midazolam and talinolol were
      administered and blood samples were obtained. Midazolam and talinolol
      pharmacokinetic parameter values were calculated and compared before and after
      genistein administration. Co-administration of genistein decreased the area under
      the concentration-time curve from 0 to 36 h (AUC 0-36) (143.65 +/- 55.40 ng h/mL
      versus 126.10 +/- 40.14 ng h/mL, p < 0.05), and the area under the concentration
      time curve from zero to infinity (AUC 0-infinity) (209.18 +/- 56.61 ng h/mL
      versus 180.59 +/- 43.03 ng h/mL, p < 0.05), and also maximum concentration (Cmax)
      of midazolam (48.86 +/- 20.21 ng/mL versus 36.25 +/- 14.35 ng/mL p < 0.05).
      Similarly, AUC 0-36 (2490.282 +/- 668.79 ng h/mL versus 2114.46 +/- 861.11 ng
      h/mL, p < 0.05), AUC 0-infinity (2980.45 +/- 921.09 ng h/mL versus 2626.92 +/-
      1003.78 ng h/mL, p < 0.05) and Cmax of talinolol (326.58 +/- 197.67 ng/mL versus
      293.42 +/- 127.19 ng/mL, p < 0.05) were reduced by genistein co-administration.
      The oral clearance of midazolam (1.68 +/- 0.85 h-1 versus 3.98 +/- 0.59 h-1, p <
      0.05) and talinolol (3.34 +/- 1.24 h-1 versus 3.79 +/- 1.55 h-1, p<0.05) were
      increased by genistien significantly. Administration of genistein can result in a
      modest induction of CYP3A and possibly P-gp activity in healthy volunteers.

PMID- 21943318
TI  - Movement control exercise versus general exercise to reduce disability in
      patients with low back pain and movement control impairment. A randomised
      controlled trial.
AB  - BACKGROUND: Non-specific low back pain (NSLBP) in subacute and chronic stages can
      be treated effectively with exercise therapy. Research guidelines recommend
      evaluating different treatments in defined subgroups of patients with NSLBP. A
      subgroup of patients with movement control impairment (MCI) improved
      significantly on patient specific function and disability in a previous case
      series after movement control exercises. METHODS/DESIGN: In a randomised
      controlled trial (RCT) we will compare the effectiveness of movement control and
      general exercise in patients with MCI. 106 participants aged 18 - 75 will be
      recruited in 5 outpatient hospital departments and 7 private practices.Patients
      randomly assigned to the movement control exercise group will be instructed to
      perform exercises according to their MCI. The general exercise group will follow
      an exercise protocol aimed at improving endurance and flexibility. Patients in
      both groups will receive 9 - 18 treatments and will be instructed to do
      additional exercises at home.The primary outcome is the level of disability
      assessed using the patient specific functional scale (PSFS) which links the
      perceived pain to functional situations and is measured before treatment and at 6
      and 12 months follow-up. Secondary outcomes concern low back pain related
      disability (Roland Morris questionnaire, RMQ), graded chronic pain scale (GCPS),
      range of motion and tactile acuity. DISCUSSION: To our knowledge this study will
      be the first to compare two exercise programs for a specific subgroup of patients
      with NSLBP and MCI. Results of this study will provide insight into the
      effectiveness of movement control exercise and contribute to our understanding of
      the mechanisms behind MCI and its relation to NSLBP. TRIAL REGISTRATION: Current
      Controlled Trials ISRCTN80064281.

PMID- 21943319
TI  - Gene expression profiles are altered in human papillomavirus-16 E6 D25E
      expressing cell lines.
AB  - Previously, we have reported that the human papillomavirus (HPV) type 16 E6 D25E
      is the most prevalent variant in Korean women at high risk for cervical cancers.
      Several studies have identified an association between the increased frequency of
      this variant and the elevated risk of cervical intraepithelial neoplasia and
      invasive cervical carcinoma. To investigate whether the HPV-16 E6 D25E variant
      might influence cervical cancer progression, we used an oligonucleotide
      microarray approach to identify transcriptionally altered gene expression
      patterns in recombinant wild-type E6 or E6 D25E variant-expressing HPV-negative
      cancer cells. We found that 211 genes were significantly up- or down-regulated
      (at least 1.5-fold, p < 0.05). We identified 14 genes, nine down-regulated and
      five up-regulated upon E6 D25E expression, compared with wild-type E6 expression.
      These results further emphasize the unique biological activity of the HPV-16 E6
      D25E variant.

PMID- 21943320
TI  - Efficacy of a hybrid assistive limb in post-stroke hemiplegic patients: a
      preliminary report.
AB  - BACKGROUND: Robotic devices are expected to be widely used in various
      applications including support for the independent mobility of the elderly with
      muscle weakness and people with impaired motor function as well as support for
      nursing care that involves heavy laborious work. We evaluated the effects of a
      hybrid assistive limb robot suit on the gait of stroke patients undergoing
      rehabilitation. METHODS: The study group comprised 16 stroke patients with severe
      hemiplegia. All patients underwent gait training. Four patients required
      assistance, and 12 needed supervision while walking. The stride length, walking
      speed and physiological cost index on wearing the hybrid assistive limb suit and
      a knee-ankle-foot orthosis were compared. RESULTS: The hybrid assistive limb suit
      increased the stride length and walking speed in 4 of 16 patients. The patients
      whose walking speed decreased on wearing the hybrid assistive limb suit either
      had not received sufficient gait training or had an established gait pattern with
      a knee-ankle-foot orthosis using a quad cane. The physiological cost index
      increased after wearing the hybrid assistive limb suit in 12 patients, but
      removal of the suit led to a decrease in the physiological cost index values to
      equivalent levels prior to the use of the suit. CONCLUSIONS: Although the hybrid
      assistive limb suit is not useful for all hemiplegic patients, it may increase
      the walking speed and affect the walking ability. Further investigation would
      clarify its indication for the possibility of gait training.

PMID- 21943321
TI  - Biomedical potential of silver nanoparticles synthesized from calli cells of
      Citrullus colocynthis (L.) Schrad.
AB  - BACKGROUND: An increasingly common application is the use of silver nanoparticles
      for antimicrobial coatings, wound dressings, and biomedical devices. In this
      present investigation, we report, biomedical potential of silver nanopaticles
      synthesized from calli extract of Citrullus colocynthis on Human epidermoid
      larynx carcinoma (HEp -2) cell line. METHODS: The callus extract react with
      silver nitrate solution confirmed silver nanoparticles synthesis through the
      steady change of greenish colour to reddish brown and characterized by using FT
      IR, AFM. Toxicity on HEp 2 cell line assessed using MTT assay, caspase -3 assay,
      Lactate dehydrogenase leakage assay and DNA fragmentation assay. RESULTS: The
      synthesized silver nanoparticles were generally found to be spherical in shape
      with size 31 nm by AFM. The molar concentration of the silver nanoparticles
      solution in our present study is 1100 nM/10 mL. The results exhibit that silver
      nanoparticles mediate a dose-dependent toxicity for the cell tested, and the
      silver nanoparticles at 500 nM decreased the viability of HEp 2 cells to 50% of
      the initial level. LDH activities found to be significantly elevated after 48 h
      of exposure in the medium containing silver nanoparticles when compared to the
      control and Caspase 3 activation suggested that silver nanoparticles caused cell
      death through apoptosis, which was further supported by cellular DNA
      fragmentation, showed that the silver nanoparticles treated HEp2 cells exhibited
      extensive double strand breaks, thereby yielding a ladder appearance (Lane 2),
      while the DNA of control HEp2 cells supplemented with 10% serum exhibited minimum
      breakage (Lane 1). This study revealed completely would eliminate the use of
      expensive drug for cancer treatment.

PMID- 21943322
TI  - Transumbilical laparo-endoscopic single site surgery for adrenal cortical adenoma
      inducing primary aldosteronism: initial experience.
AB  - BACKGROUND: We have started using laparo-endoscopic single-site surgery (LESS) in
      urologic surgery, although its use has not gained momentum due to its level of
      difficulty. We here report our initial experience with transumbilical LESS for
      adrenal cortical adenoma by using a single port with a multichannel cannula (SILS
      port) and bent laparoscopic instrumentation. FINDINGS: A multichannel port (SILS
      port), bent laparoscopic instrument (Roticulator Endo Mini-Shears) and Opti4
      laparoscopic electrodes were used in all cases. The intraperitoneal space was
      approached through the umbilicus. The SILS port was placed through a 2 cm
      incision at the inner edge of the umbilicus. A 5 mm flexible laparoscope was
      introduced to keep the laparoscope outside, and surgical specimens were extracted
      using an Endocatch bag. In addition, as a case control study, we compared
      perioperative data of LESS adrenalectomy (LESS-A) with that of conventional
      laparoscopic adrenalectomy (LA). We performed transumbilical LESS-A for adrenal
      cortical adenoma in 12 cases, beginning in December, 2009. All procedures were
      successfully completed, with only one incision through the umbilicus, and without
      conversion to a standard laparoscopic approach. Mean operative time for LESS-A
      was 121.2 +/- 7.8 min, which was slightly longer than LA (110.2 +/- 7.3 min). For
      right adrenal tumors, we used a miniport (2 mm port) in addition to a SILS port,
      and were able to successfully perform adrenalectomy "with no visible scaring".
      Tumor laterality and patient BMI did not affect surgical morbidity in these
      procedures. Moreover, there was no significant difference between LESS-A and LA
      in blood loss, analgesic requirement, hospital stay, and scar satisfaction.
      CONCLUSIONS: The transumbilical approach in LESS for adrenalectomy is safe and
      feasible and also improves cosmetic outcome compared with standard laparoscopic
      procedures. Improvements in surgical devices may aid the further development of
      this approach.

PMID- 21943323
TI  - Differential gene expression profiling of human bone marrow-derived mesenchymal
      stem cells during adipogenic development.
AB  - BACKGROUND: Adipogenesis is the developmental process by which mesenchymal stem
      cells (MSC) differentiate into pre-adipocytes and adipocytes. The aim of the
      study was to analyze the developmental strategies of human bone marrow MSC
      developing into adipocytes over a defined time scale. Here we were particularly
      interested in differentially expressed transcription factors and biochemical
      pathways. We studied genome-wide gene expression profiling of human MSC based on
      an adipogenic differentiation experiment with five different time points (day 0,
      1, 3, 7 and 17), which was designed and performed in reference to human fat
      tissue. For data processing and selection of adipogenic candidate genes, we used
      the online database SiPaGene for Affymetrix microarray expression data. RESULTS:
      The mesenchymal stem cell character of human MSC cultures was proven by cell
      morphology, by flow cytometry analysis and by the ability of the cells to develop
      into the osteo-, chondro- and adipogenic lineage. Moreover we were able to detect
      184 adipogenic candidate genes (85 with increased, 99 with decreased expression)
      that were differentially expressed during adipogenic development of MSC and/or
      between MSC and fat tissue in a highly significant way (p < 0.00001).
      Subsequently, groups of up- or down-regulated genes were formed and analyzed with
      biochemical and cluster tools. Among the 184 genes, we identified already known
      transcription factors such as PPARG, C/EBPA and RTXA. Several of the genes could
      be linked to corresponding biochemical pathways like the adipocyte
      differentiation, adipocytokine signalling, and lipogenesis pathways. We also
      identified new candidate genes possibly related to adipogenesis, such as SCARA5,
      coding for a receptor with a putative transmembrane domain and a collagen-like
      domain, and MRAP, encoding an endoplasmatic reticulum protein. CONCLUSIONS:
      Comparing differential gene expression profiles of human MSC and native fat cells
      or tissue allowed us to establish a comprehensive differential kinetic gene
      expression network of adipogenesis. Based on this, we identified known and
      unknown genes and biochemical pathways that may be relevant for adipogenic
      differentiation. Our results encourage further and more focused studies on the
      functional relevance of particular adipogenic candidate genes.

PMID- 21943324
TI  - Variable-angle total internal reflection fluorescence microscopy of intact cells
      of Arabidopsis thaliana.
AB  - BACKGROUND: Total internal reflection fluorescence microscopy (TIRFM) is a
      powerful tool for observing fluorescently labeled molecules on the plasma
      membrane surface of animal cells. However, the utility of TIRFM in plant cell
      studies has been limited by the fact that plants have cell walls, thick
      peripheral layers surrounding the plasma membrane. Recently, a new technique
      known as variable-angle epifluorescence microscopy (VAEM) was developed to
      circumvent this problem. However, the lack of a detailed analysis of the optical
      principles underlying VAEM has limited its applications in plant-cell biology.
      RESULTS: Here, we present theoretical and experimental evidence supporting the
      use of variable-angle TIRFM in observations of intact plant cells. We show that
      when total internal reflection occurs at the cell wall/cytosol interface with an
      appropriate angle of incidence, an evanescent wave field of constant depth is
      produced inside the cytosol. Results of experimental TIRFM observations of the
      dynamic behaviors of phototropin 1 (a membrane receptor protein) and clathrin
      light chain (a vesicle coat protein) support our theoretical analysis.
      CONCLUSIONS: These findings demonstrate that variable-angle TIRFM is appropriate
      for quantitative live imaging of cells in intact tissues of Arabidopsis thaliana.

PMID- 21943325
TI  - Primary care clinician adherence to guidelines for the management of chronic
      musculoskeletal pain: results from the study of the effectiveness of a
      collaborative approach to pain.
AB  - OBJECTIVE: We assessed primary care clinician-provided guideline-concordant care
      as documented in patients' medical records, predictors of documented guideline
      concordant care, and its association with pain-related functioning. Patients were
      participants in a randomized trial of collaborative care for chronic
      musculoskeletal pain. The intervention featured patient and primary care
      clinician education, symptom monitoring and feedback to clinicians by the
      intervention team. METHODS: To assess concordance with the evidence-based
      treatment guidelines upon which our intervention was based, we developed an 8
      item chart review tool, the Pain Process Checklist (PPC). We then reviewed
      electronic medical records for 365 veteran patients treated by 42 primary care
      clinicians over 12 months. Intervention status, demographic, and clinical
      variables were tested as predictors of PPC scores using generalized estimating
      equations (GEE). GEE was also used to test whether PPC scores predicted treatment
      response (>=30% decrease in Roland-Morris Disability Questionnaire score).
      RESULTS: Rates of documented guideline-concordant care varied widely among PPC
      items, from 94% of patients having pain addressed to 17% of patients on opioids
      having side effects addressed. Intervention status was unrelated to item scores,
      and PPC-7 totals did not differ significantly between intervention and treatment
      as-usual patients (61.2%, standard error [SE] = 3.3% vs 55.2%, SE = 2.6%, P =
      0.15). In a multivariate model, higher PPC-7 scores were associated with
      receiving a prescription for opioids (odds ratio [OR] = 1.07, P = 0.007) and
      lower PPC-7 scores with patient age (10-year difference OR = 0.97, P = 0.004).
      Finally, intervention patients who received quantitative pain and depression
      assessments were less likely to respond to treatment (assessed vs not: 18% vs
      33%, P = 0.008, and 13% vs 28%, P = 0.001, respectively). CONCLUSIONS: As
      measured by medical record review, additional training and clinician feedback did
      not increase provision of documented guideline-concordant pain care, and
      adherence to guidelines by primary care clinicians did not improve clinical
      outcomes for patients with chronic musculoskeletal pain.

PMID- 21943326
TI  - Retroviruses and retroelements in diseases and in gene therapy: 15 years later.
AB  - The past 15 years opened new avenues for retrovirus and retroelement research.
      Not surprisingly, they stemmed from essential knowledge collected in the past,
      which remains the ground of the present and therefore should be remembered.
      However, a short supplement of new break-through discoveries and ideas should be
      recollected. Using selected examples of recent works, I tried to extend and
      supplement my original article published in Folia Biologica (1996).

PMID- 21943327
TI  - Behavioral pharmacogenetic analysis on the role of the alpha4 GABA(A) receptor
      subunit in the ethanol-mediated impairment of hippocampus-dependent contextual
      learning.
AB  - BACKGROUND: A major effect of low-dose ethanol is impairment of hippocampus
      dependent cognitive function. alpha4/delta -containing GABA(A) Rs are highly
      expressed within the dentate gyrus region of the hippocampus where they mediate a
      tonic inhibitory current that is sensitive to the enhancement by low ethanol
      concentrations. These receptors are also powerful modulators of learning and
      memory, suggesting that they could play an important role in ethanol's cognitive
      impairing effects. The goal of this study was to develop a high-throughput
      cognitive ethanol assay, amenable to use in genetically modified mice that could
      be used to test this hypothesis. METHODS: We developed a procedure where
      preexposure to a conditioning chamber is used to rescue the "immediate shock
      deficit." Using this task, ethanol can be specifically targeted at the
      hippocampus-dependent process of contextual learning without interfering with
      pain sensitivity or behavioral performance. RESULTS: Validation of this task in
      C57BL/6 mice indicated that 1.0 g/kg ethanol and 10 mg/kg allopregnanolone
      disrupt contextual learning. Ro15-4513 reversed the effects of ethanol but not
      allopregnanolone, whereas it produced an impairment when given alone. The high
      throughput nature of this task allowed for its application in a large cohort of
      alpha4 GABA(A) R KO mice. Loss of the alpha4 GABA(A) R subunit produced an
      enhanced sensitivity to the cognitive impairing effects of ethanol. This is
      consistent with the enhanced ethanol sensitivity of synaptic GABA(A) Rs that has
      been previously observed in the dentate gyrus in these mice, but inconsistent
      with the reduced ethanol sensitivity of extrasynaptic GABA(A) Rs observed in the
      same cells. CONCLUSIONS: Overall, these findings are consistent with our
      hypothesis that ethanol acts directly at GABA(A) receptors to impair hippocampus
      dependent cognitive function. Furthermore, validation of this high-throughput
      assay will allow for future studies to use anatomically and temporally restricted
      genetic manipulations to probe more deeply into the neural mechanisms of ethanol
      action on learning and memory circuits.

PMID- 21943328
TI  - Work related characteristics, work-home and home-work interference and burnout
      among primary healthcare physicians: a gender perspective in a Serbian context.
AB  - BACKGROUND: Little information exists on work and stress related health of
      medical doctors in non-EU countries. Filling this knowledge gap is needed to
      uncover the needs of this target population and to provide information on
      comparability of health related phenomena such as burnout across countries. This
      study examined work related characteristics, work-home and home-work interference
      and burnout among Serbian primary healthcare physicians (PHPs) and compared
      burnout levels with other medical doctors in EU countries. METHODS: Data were
      collected via surveys which contained Maslach Burnout Inventory and other
      validated instruments measuring work and home related characteristics. The sample
      consisted of 373 PHPs working in 12 primary healthcare centres. Data were
      analysed using t-tests and Chi square tests. RESULTS: No gender differences were
      detected on mean scores of variables among Serbian physicians, who experience
      high levels of personal accomplishment, workload, job control and social support,
      medium to high levels of emotional exhaustion, medium levels of depersonalisation
      and work-home interference, and low levels of home-work interference. There were
      more women than men who experienced low job control and high depersonalisation.
      Serbian physicians experienced significantly higher emotional exhaustion and
      lower depersonalisation than physicians in some other European countries.
      CONCLUSIONS: To diminish excessive workload, the number of physicians working in
      primary healthcare centres in Serbia should be increased. Considering that
      differences between countries were detected on all burnout subcomponents, work
      related interventions for employees should be country specific. The role of
      gender needs to be closely examined in future studies as well.

PMID- 21943329
TI  - Attitudes and burden in relatives of patients with schizophrenia in a middle
      income country.
AB  - ABSTRACT:  BACKGROUND: Most studies of family attitudes and burden have been
      conducted in developed countries. Thus it is important to test the
      generalizability of this research in other contexts where social conditions and
      extended family involvement may be different. The aim of this study was to assess
      the relationship between the attitudes of caregivers and the burden they
      experience in such a context, namely Arica, a town located in the northernmost
      region of Chile, close to the border with Peru and Bolivia. METHODS: We assessed
      attitudes towards schizophrenia (including affective, cognitive and behavioural
      components) and burden (including subjective distress, rejection and competence)
      in 41 main caregivers of patients with schizophrenia, all of whom were users of
      Public Mental Health Services in Arica. RESULTS: Attitude measures differed
      significantly according to socio-demographic variables, with parents (mainly
      mothers) exhibiting a more negative attitude towards the environment than the
      rest of the family (t = 4.04; p = 0.000).This was also the case for caregivers
      with a low educational level (t = 3.27; p < 0.003), for the oldest caregivers (r
      = 0.546; p = 0.000) and for those who had spent more time with the patient (r =
      0.377; p = 0.015). Although attitudes had significant association with burden,
      their explanatory power was modest (R2 = .104, F = 4,55; p = .039). CONCLUSIONS:
      Similar to finding developed countries, the current study revealed a positive and
      significant relationship between the attitudes of caregivers and their burden.
      These findings emphasize the need to support the families of patients with
      schizophrenia in this social context.

PMID- 21943330
TI  - Shuttle-like supramolecular nanostructures formed by self-assembly of a porphyrin
      via an oil/water system.
AB  - In this paper, in terms of the concentration of an aqueous solution of a
      surfactant, we investigate the self-assembly behavior of a porphyrin, 5, 10, 15,
      20-tetra(4-pyridyl)-21H, 23H-porphine [H2TPyP], by using an oil/water system as
      the medium. We find that when a chloroform solution of H2TPyP is dropwise added
      into an aqueous solution of cetyltrimethylammonium bromide [CTAB] with a lower
      concentration, a large amount of irregular nanoarchitectures, together with a
      small amount of well-defined shuttle-like nanostructures, hollow nanospheres, and
      nanotubes, could be produced. While a moderate amount of shuttle-like
      nanostructures accompanied by a few irregular nanoarchitectures, solid
      nanospheres, and nanorods are produced when a CTAB aqueous solution in moderate
      concentration is employed, in contrast, a great quantity of shuttle-like
      nanostructures together with a negligible amount of solid nanospheres,
      nanofibers, and irregular nanostructures are manufactured when a high
      concentration CTAB aqueous solution is involved. An explanation on the basis of
      the molecular geometry of H2TPyP and in terms of the intermolecular pi-pi
      interactions between H2TPyP units, and hydrophobic interactions between CTAB and
      H2TPyP has been proposed. The investigation gives deep insights into the self
      assembly behavior of porphyrins in an oil/water system and provides important
      clues concerning the design of appropriate porphyrins when related subjects are
      addressed. Our investigation suggests that an oil/aqueous system might be an
      efficient medium for producing unique organic-based nanostructures.

PMID- 21943331
TI  - A prospective study of nutrition education and oral nutritional supplementation
      in patients with Alzheimer's disease.
AB  - BACKGROUND: Weight loss in patients with Alzheimer's disease (AD) is a common
      clinical manifestation that may have clinical significance. OBJECTIVES: To
      evaluate if there is a difference between nutrition education and oral
      nutritional supplementation on nutritional status in patients with AD. METHODS: A
      randomized, prospective 6-month study which enrolled 90 subjects with probable AD
      aged 65 years or older divided into 3 groups: Control Group (CG) [n = 27],
      Education Group (EG) [n = 25], which participated in an education program and
      Supplementation Group (SG) [n = 26], which received two daily servings of oral
      nutritional supplementation. Subjects were assessed for anthropometric data
      (weight, height, BMI, TSF, AC and AMC), biochemical data (total protein, albumin,
      and total lymphocyte count), CDR (Clinical Dementia Rating), MMSE (Mini-mental
      state examination), as well as dependence during meals. RESULTS: The SG showed a
      significant improvement in the following anthropometric measurements: weight (H
      calc = 22.12, p =< 0.001), BMI (H calc = 22.12, p =< 0.001), AC (H calc = 12.99,
      p =< 0.002), and AMC (H calc = 8.67, p =< 0.013) compared to the CG and EG. BMI
      of the EG was significantly greater compared to the CG. There were significant
      changes in total protein (H calc = 6.17, p =< 0.046), and total lymphocyte count
      in the SG compared to the other groups (H cal = 7.94, p = 0.019). CONCLUSION:
      Oral nutritional supplementation is more effective compared to nutrition
      education in improving nutritional status.

PMID- 21943332
TI  - Who applies and who gets admitted to UK graduate entry medicine? - An analysis of
      UK admission statistics.
AB  - BACKGROUND: Graduate-entry medicine is a recent development in the UK, intended
      to expand and broaden access to medical training. After eight years, it is time
      to evaluate its success in recruitment. OBJECTIVES: This study aimed to compare
      the applications and admissions profiles of graduate-entry programmes in the UK
      to traditional 5 and 6-year courses. METHODS: Aggregate data on applications and
      admissions were obtained from the Universities and Colleges Admission Service
      covering 2003 to 2009. Data were extracted, grouped as appropriate and analysed
      with the Statistical Package for the Social Sciences. RESULTS: Graduate-entry
      attracts 10,000 applications a year. Women form the majority of applicants and
      admissions to graduate-entry and traditional medicine programmes. Graduate-entry
      age profile is older, typically 20's or 30's compared to 18 or 19 years in
      traditional programmes. Graduate-entry applications and admissions were higher
      from white and black UK ethnic communities than traditional programmes, and lower
      from southern and Chinese Asian groups. Graduate-entry has few applications or
      admissions from Scotland or Northern Ireland. Secondary educational achievement
      is poorer amongst graduate-entry applicants and admissions than traditional
      programmes. CONCLUSIONS: Graduate-entry has succeeded in recruiting substantial
      additional numbers of older applicants to medicine, in which white and black
      groups are better represented and Asian groups more poorly represented than in
      traditional undergraduate programmes.

PMID- 21943334
TI  - The interaction of the second Kunitz-type domain (KD2) of TFPI-2 with a novel
      interaction partner, prosaposin, mediates the inhibition of the invasion and
      migration of human fibrosarcoma cells.
AB  - TFPI-2 (tissue factor pathway inhibitor-2) has recently been recognized as a new
      tumour suppressor gene. Low expression of this protein in several types of
      cancers allows for enhanced tumour growth, invasion and metastasis. To
      investigate the molecular mechanism responsible for the tumour-suppressor effects
      of TFPI-2, we performed yeast two-hybrid analysis and identified PSAP
      (prosaposin) as a TFPI-2-interacting partner. This interaction was confirmed by
      co-immunoprecipitation and immunofluorescence. The region of TFPI-2 that
      interacts with PSAP is located in the KD2 (Kunitz-type domain 2). Further study
      showed that PSAP does not affect the function of TFPI-2 as a serine proteinase
      inhibitor, but that TFPI-2 could inhibit the invasion-promoting effects of PSAP
      in human HT1080 fibrosarcoma cells. The results of the present study revealed
      that TFPI-2 interacts with PSAP, which may play an important role in the
      physiology and pathology of diseases such as cancer.

PMID- 21943333
TI  - Prediction of protein-binding areas by small-world residue networks and
      application to docking.
AB  - BACKGROUND: Protein-protein interactions are involved in most cellular processes,
      and their detailed physico-chemical and structural characterization is needed in
      order to understand their function at the molecular level. In-silico docking
      tools can complement experimental techniques, providing three-dimensional
      structural models of such interactions at atomic resolution. In several recent
      studies, protein structures have been modeled as networks (or graphs), where the
      nodes represent residues and the connecting edges their interactions. From such
      networks, it is possible to calculate different topology-based values for each of
      the nodes, and to identify protein regions with high centrality scores, which are
      known to positively correlate with key functional residues, hot spots, and
      protein-protein interfaces. RESULTS: Here we show that this correlation can be
      efficiently used for the scoring of rigid-body docking poses. When integrated
      into the pyDock energy-based docking method, the new combined scoring function
      significantly improved the results of the individual components as shown on a
      standard docking benchmark. This improvement was particularly remarkable for
      specific protein complexes, depending on the shape, size, type, or flexibility of
      the proteins involved. CONCLUSIONS: The network-based representation of protein
      structures can be used to identify protein-protein binding regions and to
      efficiently score docking poses, complementing energy-based approaches.

PMID- 21943335
TI  - Alu pair exclusions in the human genome.
AB  - BACKGROUND: The human genome contains approximately one million Alu elements
      which comprise more than 10% of human DNA by mass. Alu elements possess
      direction, and are distributed almost equally in positive and negative strand
      orientations throughout the genome. Previously, it has been shown that closely
      spaced Alu pairs in opposing orientation (inverted pairs) are found less
      frequently than Alu pairs having the same orientation (direct pairs). However,
      this imbalance has only been investigated for Alu pairs separated by 650 or fewer
      base pairs (bp) in a study conducted prior to the completion of the draft human
      genome sequence. RESULTS: We performed a comprehensive analysis of all (>
      800,000) full-length Alu elements in the human genome. This large sample size
      permits detection of small differences in the ratio between inverted and direct
      Alu pairs (I:D). We have discovered a significant depression in the full-length
      Alu pair I:D ratio that extends to repeat pairs separated by <= 350,000 bp.
      Within this imbalance bubble (those Alu pairs separated by <= 350,000 bp), direct
      pairs outnumber inverted pairs. Using PCR, we experimentally verified several
      examples of inverted Alu pair exclusions that were caused by deletions.
      CONCLUSIONS: Over 50 million full-length Alu pairs reside within the I:D
      imbalance bubble. Their collective impact may represent one source of Alu element
      related human genomic instability that has not been previously characterized.

PMID- 21943336
TI  - Patient and physician perceptions on continuing aromatase inhibitors beyond the 5
      year mark.
AB  - Aromatase inhibitors (AIs) have been shown to improve disease-free survival and
      in certain cases, overall survival in the treatment of postmenopausal women with
      hormone receptor positive early breast cancer. Trials are ongoing to determine if
      AI therapy should be continued for patients who have already completed 5 years of
      AI treatment. The objective of this study was to assess the minimum disease-free
      and overall survival benefit acceptable to physicians and to women undergoing AI
      therapy to continue treatment beyond 5 years. A self-administered survey was
      completed by women with stage I-III breast cancer, who were undergoing adjuvant
      AI therapy for at least 1 year. The survey assessed relevant cancer-related,
      treatment, social and comorbid factors, and FACT-ES (V4). Minimum acceptable
      treatment benefit was denoted as a percentage decrease in cancer recurrence risk,
      and percentage increase in survival at 5 years. Medical oncologists (MOs)
      treating breast cancer across Canada were also surveyed. A total of 153 patients
      were surveyed; median age was 60, 51% had node-negative disease, 89% had prior
      radiation therapy, 61% had prior chemotherapy, and 59% had prior tamoxifen
      therapy. Mean duration of AI therapy was 31 months. Approximately 30% of women
      required a 5-year survival benefit of less than 1%, and 27.5% needed a decrease
      in risk of recurrence of less than 1% to continue an AI beyond the initial 5
      years. In contrast, 45% of the 40 surveyed MOs required a 5-year survival benefit
      of at least 1-2%, and 37.5% preferred a decrease in recurrence risk of 2-5% to
      prescribe an AI for an additional 5 years. There was a significant correlation
      between severity of endocrine symptoms experienced on AIs and an increased
      minimum survival benefit required for women to continue therapy (r = 0.18, p =
      0.036). Patients were willing to continue on AIs for smaller treatment benefits
      than physicians would prefer to prescribe them beyond 5 years. Patient preference
      to continue on AIs correlated somewhat to the severity of AI-related side
      effects.

PMID- 21943337
TI  - Generation of a recombinant rabies Flury LEP virus carrying an additional G gene
      creates an improved seed virus for inactivated vaccine production.
AB  - The rabies Flury Low Egg Passage virus (LEP) has been widely used as a seed virus
      to generate inactive vaccine. Here, we established a reverse genetic system for
      LEP and generated a recombinant LEP virus (rLEP-G) that carries two identical G
      genes. This recombinant virus showed similar properties to those of LEP with
      respect to in vitro growth, neurotropism index, and virulence in mice. rLEP-G
      produced 4.3-fold more G protein than did LEP in BHK-21 cells. The inactivated
      vaccine generated from rLEP-G induced significantly higher virus neutralization
      titers in mice and dogs than those produced in response to LEP-derived vaccine.
      Our results suggest that rLEP-G is an improved seed virus candidate for
      inactivated rabies virus vaccine manufacture.

PMID- 21943338
TI  - TIGER: Toolbox for integrating genome-scale metabolic models, expression data,
      and transcriptional regulatory networks.
AB  - BACKGROUND: Several methods have been developed for analyzing genome-scale models
      of metabolism and transcriptional regulation. Many of these methods, such as Flux
      Balance Analysis, use constrained optimization to predict relationships between
      metabolic flux and the genes that encode and regulate enzyme activity. Recently,
      mixed integer programming has been used to encode these gene-protein-reaction
      (GPR) relationships into a single optimization problem, but these techniques are
      often of limited generality and lack a tool for automating the conversion of
      rules to a coupled regulatory/metabolic model. RESULTS: We present TIGER, a
      Toolbox for Integrating Genome-scale Metabolism, Expression, and Regulation.
      TIGER converts a series of generalized, Boolean or multilevel rules into a set of
      mixed integer inequalities. The package also includes implementations of existing
      algorithms to integrate high-throughput expression data with genome-scale models
      of metabolism and transcriptional regulation. We demonstrate how TIGER automates
      the coupling of a genome-scale metabolic model with GPR logic and models of
      transcriptional regulation, thereby serving as a platform for algorithm
      development and large-scale metabolic analysis. Additionally, we demonstrate how
      TIGER's algorithms can be used to identify inconsistencies and improve existing
      models of transcriptional regulation with examples from the reconstructed
      transcriptional regulatory network of Saccharomyces cerevisiae. CONCLUSION: The
      TIGER package provides a consistent platform for algorithm development and
      extending existing genome-scale metabolic models with regulatory networks and
      high-throughput data.

PMID- 21943339
TI  - Prognostic factors in non-surgically treated sciatica: a systematic review.
AB  - BACKGROUND: When present sciatica is considered an obstacle to recovery in low
      back pain patients, yet evidence is limited regarding prognostic factors for
      persistent disability in this patient group. The aim of this study is to describe
      and summarise the evidence regarding prognostic factors for sciatica in non
      surgically treated cohorts. Understanding the prognostic factors in sciatica and
      their relative importance may allow the identification of patients with
      particular risk factors who might benefit from early or specific types of
      treatment in order to optimise outcome. METHODS: A systematic literature search
      was conducted using Medline, EMBASE and CINAHL electronic databases. Prospective
      cohort studies describing subjects with sciatica and measuring pain, disability
      or recovery outcomes were included. Studies of cohorts comprised entirely of
      surgically treated patients were excluded and mixed surgically and conservatively
      treated cohorts were included only if the results were analysed separately by
      treatment group or if the analysis was adjusted for treatment. RESULTS: Seven
      adequate or high quality eligible studies were identified. There were conflicting
      but mainly negative results regarding the influence of baseline pain severity,
      neurological deficit, nerve root tension signs, duration of symptoms and
      radiological findings on outcome. A number of factors including age, gender,
      smoking, previous history of sciatica and heaviness of work do not appear to
      influence outcome. In contrast to studies of low back pain and purely surgically
      treated sciatica cohorts, psychological factors were rarely investigated.
      CONCLUSIONS: At present, the heterogeneity of the available studies makes it
      difficult to draw firm conclusions about sciatica prognosis, and highlights the
      need for further research for this group of patients. Large scale prospective
      studies of high methodological quality, using a well-defined, consistent
      definition of sciatica and investigating psychosocial factors alongside clinical
      and radiological findings are recommended to identify prognostic factors in this
      population.

PMID- 21943340
TI  - Hypoxia-mediated efficient expansion of human tendon-derived stem cells in vitro.
AB  - Tendons regenerate and repair slowly and inefficiently after injury. Tendon
      derived stem cells (TDSCs) have been isolated recently and have been shown to
      promote tendon repair. The ability to achieve sufficient numbers of cells for
      transplantation is essential for their clinical application. In this study, we
      aimed to study the effect of low oxygen (O(2)) tension (2%) on the clonogenicity,
      metabolic rate, DNA incorporation, population doubling time, beta-galactosidase
      activity, immunophenotypes, multilineage differentiation potential, and tenocyte
      like properties of human TDSCs (hTDSCs). hTDSCs were isolated from patellar
      tendon and characterized according to their adherence to plastic; colony-forming
      ability; multilineage differentiation potential; and high expression level of
      CD44, CD73, CD 90, and CD105 but low CD34, CD45, CD146, and Stro-1 at 20% O(2)
      tension. Low O(2) tension increased DNA incorporation but not metabolic rate of
      hTDSCs. It increased cell number 25% and the number of colonies but reduced the
      osteogenic, adipogenic, and chondrogenic differentiation potential of hTDSCs. The
      reduction in differentiation potential was associated with lower messenger RNA
      (mRNA) expression ratios of some lineage-related markers, including BGLAP, ALP,
      C/EBPalpha, PPARgamma2, ACAN, and SOX9; the expression of a tendon-related
      marker, TNMD, was greater. There was no significant difference in the production
      of collagenous to noncollagenous protein ratio; the immunophenotypes and beta
      galactosidase activity were similar at 2% and 20% O(2) tension. Hypoxia
      preconditioned hTDSCs could successfully differentiate at 20% O(2) tension, as
      shown by the return of the mRNA expression ratios of lineage-related markers to
      levels comparable to cells pre-incubated and differentiated at 20% O(2) tension.
      In conclusion, hypoxia is advantageous for efficient expansion of hTDSCs in vitro
      for tendon tissue engineering.

PMID- 21943342
TI  - Surgical management of Diabetic foot ulcers: A Tanzanian university teaching
      hospital experience.
AB  - BACKGROUND: Diabetic foot ulcers (DFUs) pose a therapeutic challenge to surgeons,
      especially in developing countries where health care resources are limited and
      the vast majority of patients present to health facilities late with advanced
      foot ulcers. A prospective descriptive study was done at Bugando Medical Centre
      from February 2008 to January 2010 to describe our experience in the surgical
      management of DFUs in our local environment and compare with what is known in the
      literature. FINDINGS: Of the total 4238 diabetic patients seen at BMC during the
      period under study, 136 (3.2%) patients had DFUs. Males outnumbered females by
      the ratio of 1.2:1. Their mean age was 54.32 years (ranged 21-72years). Thirty
      eight (27.9%) patients were newly diagnosed diabetic patients. The majority of
      patients (95.5%) had type 2 diabetes mellitus. The mean duration of diabetes was
      8.2 years while the duration of DFUs was 18.34 weeks. Fourteen (10.3%) patients
      had previous history of foot ulcers and six (4.4%) patients had previous
      amputations. The forefoot was commonly affected in 60.3% of cases. Neuropathic
      ulcers were the most common type of DFUs in 57.4% of cases. Wagner's stage 4 and
      5 ulcers were the most prevalent at 29.4% and 23.5% respectively. The majority of
      patients (72.1%) were treated surgically. Lower limb amputation was the most
      common surgical procedure performed in 56.7% of cases. The complication rate was
      (33.5%) and surgical site infection was the most common complication (18.8%).
      Bacterial profile revealed polymicrobial pattern and Staphylococcus aureus was
      the most frequent microorganism isolated. All the microorganisms isolated showed
      high resistance to commonly used antibiotics except for Meropenem and imipenem,
      which were 100% sensitive each respectively. The mean hospital stay was 36.24 +/-
      12.62 days (ranged 18-128 days). Mortality rate was 13.2%. CONCLUSION: Diabetic
      foot ulceration constitutes a major source of morbidity and mortality among
      patients with diabetes mellitus at Bugando Medical Centre and is the leading
      cause of non-traumatic lower limb amputation. A multidisciplinary team approach
      targeting at good glycaemic control, education on foot care and appropriate
      footware, control of infection and early surgical intervention is required in
      order to reduce the morbidity and mortality associated with DFUs. Due to
      polymicrobial infection and antibiotic resistance, surgical intervention must be
      concerned.

PMID- 21943343
TI  - Comparative transcriptomes profiling of photoperiod-sensitive male sterile rice
      Nongken 58S during the male sterility transition between short-day and long-day.
AB  - BACKGROUND: Photoperiod-sensitive genic male sterile (PGMS) rice, Nongken 58S,
      was discovered in 1973. It has been widely used for the production of hybrid
      rice, and great achievements have been made in improving rice yields. However,
      the mechanism of the male sterility transition in PGMS rice remains to be
      determined. RESULTS: To investigate the transcriptome during the male sterility
      transition in PGMS rice, the transcriptome of Nongken 58S under short-day (SD)
      and long-day (LD) at the glume primordium differentiation and pistil/stamen
      primordium forming stages was compared. Seventy-three and 128 differentially
      expressed genes (DEGs) were identified at the glume primordium differentiation
      and pistil/stamen primordium forming stages, respectively. Five and 22 genes were
      markedly up-regulated (>= 5-fold), and two and five genes were considerably down
      regulated (>= 5-fold) under SD during the male sterility transition. Gene
      ontology annotation and pathway analysis revealed that four biological processes
      and the circadian rhythms and the flowering pathways coordinately regulated the
      male sterility transition. Further quantitative PCR analysis demonstrated that
      the circadian rhythms of OsPRR1, OsPRR37, OsGI, Hd1, OsLHY and OsDof in leaves
      were obviously different between Nongken 58S and Nongken 58 under LD conditions.
      Moreover, both OsPRR37 and Hd1 in the inflorescence displayed differences between
      Nongken 58S and Nongken 58 under both LD and SD conditions. CONCLUSION: The
      results presented here indicate that the transcriptome in Nongken 58S was
      significantly suppressed under LD conditions. Among these DEGs, the circadian
      rhythm and the flowering pathway were involved in the male sterility transition.
      Furthermore, these pathways were coordinately involved in the male sterility
      transition in PGMS rice.

PMID- 21943344
TI  - Analysis of factors associated with patient satisfaction in ophthalmology: the
      influence of demographic data, visit characteristics and perceptions of received
      care.
AB  - PURPOSE: To identify factors associated with satisfaction among patients
      receiving ophthalmic services and to indicate the intensity of this relationship.
      METHODS: The data used was obtained through a self-administered, post-visit
      questionnaire from randomly selected 507 patients treated in seven eye clinics in
      Germany. The instrument assessed satisfaction with several aspects of care and
      patient baseline and visit characteristics. Bivariate and multivariate techniques
      were used to reveal relations between indicators and overall satisfaction.
      RESULTS: Factor analysis yielded two factors, 'medical aspects of care' and
      'performance of service', explaining 55% of total variance. Cronbach's alpha
      coefficient for both scales indicates acceptable internal consistency. Bivariate
      analysis showed strong relations between overall satisfaction and perceived care
      with weaker findings pertaining to visit characteristics. Not any of the
      demographic variables was associated with overall satisfaction. Perceived length
      of stay, intention to return to the clinic, and occurrence of complications were
      influential attributes on satisfaction ratings. The multivariate analysis
      identified seven factors associated with overall satisfaction including the
      treatment outcome (OR: 4.57), kindness of the nurses (OR: 5.27) and medical
      practitioners (OR: 2.23), room amenities (OR: 2.72), organization of procedures
      and operations (OR: 2.71), information about anaesthesia (OR: 1.95), and
      cleanliness (OR: 1.93). CONCLUSIONS: Factors associated with patient satisfaction
      in ophthalmology concern medical aspects like the organization of procedures and
      operations but also aspects that are not directly related to technical care, such
      as kindness of the nurses and cleanliness. Results show that patients' subjective
      experiences of received care and services relate more strongly and consistently
      to overall satisfaction than patient demographic data or visit characteristics.
      Revealed factors predicting patient satisfaction are alterable by health care
      managers. Therefore, focusing on these attributes represents an effective manner
      to enhance patient satisfaction in ophthalmology.

PMID- 21943345
TI  - Nanoscale potassium niobate crystal structure and phase transition.
AB  - Nanoscale potassium niobate (KNbO3) powders of orthorhombic structure were
      synthesized using the sol-gel method. The heat-treatment temperature of the gels
      had a pronounced effect on KNbO3 particle size and morphology. Field emission
      scanning electron microscopy and transmission electron microscopy were used to
      determine particle size and morphology. The average KNbO3 grain size was
      estimated to be less than 100 nm, and transmission electron microscopy images
      indicated that KNbO3 particles had a brick-like morphology. Synchrotron X-ray
      diffraction was used to identify the room-temperature structures using Rietveld
      refinement. The ferroelectric orthorhombic phase was retained even for particles
      smaller than 50 nm. The orthorhombic to tetragonal and tetragonal to cubic phase
      transitions of nanocrystalline KNbO3 were investigated using temperature
      dependent powder X-ray diffraction. Differential scanning calorimetry was used to
      examine the temperature dependence of KNbO3 phase transition. The Curie
      temperature and phase transition were independent of particle size, and Rietveld
      analyses showed increasing distortions with decreasing particle size.

PMID- 21943346
TI  - Brain region specific mitophagy capacity could contribute to selective neuronal
      vulnerability in Parkinson's disease.
AB  - Parkinson's disease (PD) is histologically well defined by its characteristic
      degeneration of dopaminergic neurons in the substantia nigra pars compacta.
      Remarkably, divergent PD-related mutations can generate comparable brain region
      specific pathologies. This indicates that some intrinsic region-specificity
      respecting differential neuron vulnerability exists, which codetermines the
      disease progression. To gain insight into the pathomechanism of PD, we
      investigated protein expression and protein oxidation patterns of three different
      brain regions in a PD mouse model, the PINK1 knockout mice (PINK1-KO), in
      comparison to wild type control mice. The dysfunction of PINK1 presumably affects
      mitochondrial turnover by disturbing mitochondrial autophagic pathways. The three
      brain regions investigated are the midbrain, which is the location of substantia
      nigra; striatum, the major efferent region of substantia nigra; and cerebral
      cortex, which is more distal to PD pathology. In all three regions, mitochondrial
      proteins responsible for energy metabolism and membrane potential were
      significantly altered in the PINK1-KO mice, but with very different region
      specific accents in terms of up/down-regulations. This suggests that disturbed
      mitophagy presumably induced by PINK1 knockout has heterogeneous impacts on
      different brain regions. Specifically, the midbrain tissue seems to be most
      severely hit by defective mitochondrial turnover, whereas cortex and striatum
      could compensate for mitophagy nonfunction by feedback stimulation of other
      catabolic programs. In addition, cerebral cortex tissues showed the mildest level
      of protein oxidation in both PINK1-KO and wild type mice, indicating either a
      better oxidative protection or less reactive oxygen species (ROS) pressure in
      this brain region. Ultra-structural histological examination in normal mouse
      brain revealed higher incidences of mitophagy vacuoles in cerebral cortex than in
      striatum and substantia nigra. Taken together, the delicate balance between
      oxidative protection and mitophagy capacity in different brain regions could
      contribute to brain region-specific pathological patterns in PD.

PMID- 21943341
TI  - Reliability and validity of the Adolescent Stress Questionnaire in a sample of
      European adolescents--the HELENA study.
AB  - BACKGROUND: Since stress is hypothesized to play a role in the etiology of
      obesity during adolescence, research on associations between adolescent stress
      and obesity-related parameters and behaviours is essential. Due to lack of a well
      established recent stress checklist for use in European adolescents, the study
      investigated the reliability and validity of the Adolescent Stress Questionnaire
      (ASQ) for assessing perceived stress in European adolescents. METHODS: The ASQ
      was translated into the languages of the participating cities (Ghent, Stockholm,
      Vienna, Zaragoza, Pecs and Athens) and was implemented within the HELENA cross
      sectional study. A total of 1140 European adolescents provided a valid ASQ,
      comprising 10 component scales, used for internal reliability (Cronbach alpha)
      and construct validity (confirmatory factor analysis or CFA). Contributions of
      socio-demographic (gender, age, pubertal stage, socio-economic status)
      characteristics to the ASQ score variances were investigated. Two-hundred
      adolescents also provided valid saliva samples for cortisol analysis to compare
      with the ASQ scores (criterion validity). Test-retest reliability was
      investigated using two ASQ assessments from 37 adolescents. RESULTS: Cronbach
      alpha-values of the ASQ scales (0.57 to 0.88) demonstrated a moderate internal
      reliability of the ASQ, and intraclass correlation coefficients (0.45 to 0.84)
      established an insufficient test-retest reliability of the ASQ. The adolescents'
      gender (girls had higher stress scores than boys) and pubertal stage (those in a
      post-pubertal development had higher stress scores than others) significantly
      contributed to the variance in ASQ scores, while their age and socio-economic
      status did not. CFA results showed that the original scale construct fitted
      moderately with the data in our European adolescent population. Only in boys,
      four out of 10 ASQ scale scores were a significant positive predictor for
      baseline wake-up salivary cortisol, suggesting a rather poor criterion validity
      of the ASQ, especially in girls. CONCLUSIONS: In our European adolescent sample,
      the ASQ had an acceptable internal reliability and construct validity and the
      adolescents' gender and pubertal stage systematically contributed to the ASQ
      variance, but its test-retest reliability and criterion validity were rather
      poor. Overall, the utility of the ASQ for assessing perceived stress in
      adolescents across Europe is uncertain and some aspects require further
      examination.

PMID- 21943347
TI  - How much time is available for antenatal care consultations? Assessment of the
      quality of care in rural Tanzania.
AB  - BACKGROUND: Many women in Sub-Saharan African countries do not receive key
      recommended interventions during routine antenatal care (ANC) including
      information on pregnancy, related complications, and importance of skilled
      delivery attendance. We undertook a process evaluation of a successful cluster
      randomized trial testing the effectiveness of birth plans in increasing
      utilization of skilled delivery and postnatal care in Ngorongoro district, rural
      Tanzania, to document the time spent by health care providers on providing the
      recommended components of ANC. METHODS: The study was conducted in 16 health
      units (eight units in each arm of the trial). We observed, timed, and audio
      recorded ANC consultations to assess the total time providers spent with each
      woman and the time spent for the delivery of each component of care. T-test
      statistics were used to compare the total time and time spent for the various
      components of ANC in the two arms of the trial. We also identified the topics
      discussed during the counselling and health education sessions, and examined the
      quality of the provider-woman interaction. RESULTS: The mean total duration for
      initial ANC consultations was 40.1 minutes (range 33-47) in the intervention arm
      versus 19.9 (range 12-32) in the control arm p < 0.0001. Except for drug
      administration, which was the same in both arms of the trial, the time spent on
      each component of care was also greater in the intervention health units. Similar
      trends were observed for subsequent ANC consultations. Birth plans were always
      discussed in the intervention health units. Counselling on HIV/AIDS was also
      prioritized, especially in the control health units. Most other recommended
      topics (e.g. danger signs during pregnancy) were rarely discussed. CONCLUSION:
      Although the implementation of birth plans in the intervention health units
      improved provider-women dialogue on skilled delivery attendance, most recommended
      topics critical to improving maternal and newborn survival were rarely covered.

PMID- 21943348
TI  - Understanding the prescription of antidepressants: a Qualitative study among
      French GPs.
AB  - BACKGROUND: One-tenth of France's population is prescribed at least one
      antidepressant, primarily by General Practitioners. The reasons for this high
      prescription rate remain unclear. One-third of these prescriptions may not comply
      with clinical practice guidelines, and 20% are potentially unrelated to any
      psychiatric condition. Our aim was to explore how GPs declare they use
      antidepressants in daily practice and understand their reasons for prescribing
      them. METHOD: Six focus groups including a total of 56 rural and urban GPs, with
      four interviews were performed. The topic guide focused on reasons for
      prescribing antidepressants in various primary care situations. Phenomenological
      analysis was performed by four researchers. RESULTS: Antidepressants were seen as
      useful and not harmful. Personal assessment based on experience and feeling
      determined the GPs' decisions rather than the use of scales. Twenty-four "non
      psychiatric" conditions possibly leading to prescription of antidepressants in
      primary care were found. CONCLUSIONS: The GPs reported prescribing
      antidepressants for a wide range of conditions other than depression. The GPs'
      decision making process is difficult and complex. They seemed to prefer to focus
      on their difficulties in diagnosing depression rather than on useless
      overtreatment. Instead of using the guidelines criteria to detect potential cases
      of useful prescription, physicians tend to use their own tools based on gut
      feelings, knowledge of the patient and contextual issues.

PMID- 21943349
TI  - Classification of images of wheat, ryegrass and brome grass species at early
      growth stages using principal component analysis.
AB  - Wheat is one of the most important crops in Australia, and the identification of
      young plants is an important step towards developing an automated system for
      monitoring crop establishment and also for differentiating crop from weeds. In
      this paper, a framework to differentiate early narrow-leaf wheat from two common
      weeds from their digital images is developed. A combination of colour, texture
      and shape features is used. These features are reduced to three descriptors using
      Principal Component Analysis. The three components provide an effective and
      significant means for distinguishing the three grasses. Further analysis enables
      threshold levels to be set for the discrimination of the plant species. The PCA
      model was evaluated on an independent data set of plants and the results show
      accuracy of 88% and 85% in the differentiation of ryegrass and brome grass from
      wheat, respectively. The outcomes of this study can be integrated into new
      knowledge in developing computer vision systems used in automated weed
      management.

PMID- 21943350
TI  - GOmotif: A web server for investigating the biological role of protein sequence
      motifs.
AB  - BACKGROUND: Many proteins contain conserved sequence patterns (motifs) that
      contribute to their functionality. The process of experimentally identifying and
      validating novel protein motifs can be difficult, expensive, and time consuming.
      A means for helping to identify in advance the possible function of a novel motif
      is important to test hypotheses concerning the biological relevance of these
      motifs, thus reducing experimental trial-and-error. RESULTS: GOmotif accepts
      PROSITE and regular expression formatted motifs as input and searches a Gene
      Ontology annotated protein database using motif search tools. The search returns
      the set of proteins containing matching motifs and their associated Gene Ontology
      terms. These results are presented as: 1) a hierarchical, navigable tree
      separated into the three Gene Ontology biological domains - biological process,
      cellular component, and molecular function; 2) corresponding pie charts
      indicating raw and statistically adjusted distributions of the results, and 3) an
      interactive graphical network view depicting the location of the results in the
      Gene Ontology. CONCLUSIONS: GOmotif is a web-based tool designed to assist
      researchers in investigating the biological role of novel protein motifs. GOmotif
      can be freely accessed at http://www.gomotif.ca.

PMID- 21943351
TI  - Combination of intrathecal opioids with bupivacaine attenuates opioid dose
      escalation in chronic noncancer pain patients.
AB  - OBJECTIVE: The purpose of this study was to examine the effect of intrathecal
      (IT) coadministration of bupivacaine with opioids during the initial phase of
      opioid titration and up to 1 year after implantation of an IT drug delivery
      system (IDDS). DESIGN: The study was designed as a retrospective study. OUTCOMES
      ANALYZED: The outcomes analyzed for this study were pain relief, oral opioid
      consumption, IT opioid, and bupivacaine dosage. METHODS AND PATIENT POPULATION:
      The patient population for this study were consecutively implanted patients over
      a period of 6 years in a tertiary single center with multiple practitioners. In
      this retrospective study, 126 consecutive noncancer intractable pain patients
      were implanted with IDDS and initiated with an IT opioid (O) as a single
      medication or an IT opioid and bupivacaine (O + B). Pain intensity, amount of
      oral opioids, dose, rate, and concentration of IT opioids and bupivacaine, and
      number and type of IT medication used were recorded at preimplant, implant, and
      at 3, 6, and 12 months postimplant. INTERVENTION: The intervention used for the
      study was the IT delivery device implant. RESULTS: Significant reduction in pain
      intensity was observed in both groups at 12 months postimplant (O group: baseline
      7.42 +/- 2.1 to 5.85 +/- 2.8 [n = 72, P < 0.001]; O + B group 7.35 +/- 2 to 5.03
      +/- 2.4 (n = 54; P < 0.001]). The combination of opioids with bupivacaine from
      the start of IT infusion treatment resulted in a reduced progression of opioid
      dose escalation in comparison to patients started with opioids (O group). The
      rate of increase of IT opioids in the O group at 12 months was 535 +/- 180%,
      whereas in the O + B, the dose increase was significantly lower at 185 +/- 85% (P
      < 0.004). In both groups, there was a statistically significant decrease in oral
      opioid consumption compared with preimplant doses. CONCLUSION: Concomitant
      initial coadministration of IT bupivacaine with opioids blunts the rate of IT
      opioid dose escalation during the first year after implant of an IDDS. More
      studies are necessary to thoroughly examine IT opioid dose escalation and the
      effects of addition of bupivacaine to IT opioids. Blunting IT opioid dose
      escalation may be a beneficial long-term effect of IT bupivacaine.

PMID- 21943353
TI  - A survey of current and past Pediatric Infectious Diseases fellows regarding
      training.
AB  - BACKGROUND: The objectives of this study were to characterize the satisfaction of
      Pediatric Infectious Diseases fellows with their training and to understand how
      opinions about training have changed over time. METHODS: Anonymous survey studies
      were conducted with questions designed to include areas related to the 6 ACGME
      core competencies. Surveys for current fellows were distributed by fellowship
      directors, while surveys for graduates were mailed to all individuals with
      Pediatric Infectious Diseases certification. RESULTS: Response rates for current
      fellows and graduates were 50% and 52%, respectively. Most fellows (98%) and
      graduates (92%) perceived their overall training favorably. Training in most
      clinical care areas was rated favorably, however both groups perceived relative
      deficiencies in several areas. Current fellows rated their training in other
      competency areas (e.g., systems-based practice, research, and ethics) more
      favorably when compared to past graduates. Recent graduates perceived their
      training more favorably in many of these areas compared to past graduates.
      CONCLUSIONS: Pediatric Infectious Diseases fellowship training is well regarded
      by the majority of current and past trainees. Views of current fellows reflect
      improved satisfaction with training in a variety of competency areas. Persistent
      deficiencies in clinical training likely reflect active barriers to education.
      Additional study is warranted to validate perceived deficiencies and to establish
      consensus on the importance of these areas to infectious diseases training.

PMID- 21943352
TI  - Bioactive properties and clinical safety of a novel milk protein peptide.
AB  - BACKGROUND: Milk protein fractions and peptides have been shown to have bioactive
      properties. This preliminary study examined the potential mechanisms of action
      and clinical safety of novel milk protein peptide (MP). FINDINGS: A novel MP
      mixture inhibits the tyrosine kinase activity of epidermal growth factor receptor
      (EGFR), vascular endothelial growth factor receptor 2 (VEGFR2), and insulin
      receptor (IR) with IC50 of 9.85 MUM, 7.7 MUM, and 6.18 MUM respectively. In
      vitro, this multi-kinase inhibitor causes apoptosis in HT-29 colon cancer cells,
      and in a C. elegans worm study, showed a weak but significant increase in
      lifespan. A six week double-blind, placebo-controlled study involving 73 healthy
      volunteers demonstrated that the MP mixture is safe to consume orally. All
      clinical blood markers remained within normal levels and no clinically
      significant side effects were reported. There was some evidence of improved
      insulin sensitivity, neutrophil-to-lymphocyte ratio (NLR), and quality of life
      assessment of role of physical function. CONCLUSIONS: These data in combination
      with the observed in vitro anti-cancer properties warrant further clinical
      studies to investigate this MP mixture as a potential clinical nutrition
      intervention for improving the quality of life and clinical outcomes in cancer
      patients. TRIAL REGISTRATION: NCT01412658.

PMID- 21943354
TI  - The identification of the Romanovs: Can we (finally) put the controversies to
      rest?
AB  - For much of the 20th century the fate of the last Imperial family of Russia, the
      Romanovs, was a mystery after their execution in 1918. In the mid 1970s the mass
      grave of the Romanov family (minus two of the children) was discovered and
      officially exhumed after the fall of the Soviet Union. Forensic DNA testing of
      the remains in the early 1990s was used to identify the family. Despite the
      overwhelming evidence for establishing the identity of the Romanov family, a
      small but vocal number of scientists have tried to raise doubt about the DNA
      testing during the late 1990s and early 2000s. With the discovery of the two
      missing Romanov children in 2007, there was an opportunity to re-analyze all of
      the evidence associated with the case which confirmed the initial DNA testing and
      brought finality to the mystery. This article will discuss the controversies
      associated with the Romanov identification and reflect upon the importance of the
      case to the field of forensic DNA typing over the last 20 years.

PMID- 21943355
TI  - Severe hypertension following accidental clonidine overdose during the refilling
      of an implanted intrathecal drug delivery system.
AB  - BACKGROUND:   Complications associated with intrathecal pumps may be linked to
      the surgical procedure, the implanted device, or the medication itself. CASE
      REPORTS:   Three patients treated chronically with intrathecal clonidine
      presented with clonidine overdose due to inadvertent extravasation during the
      refilling procedure. All patients experienced loss of consciousness and severe
      systemic hypertension that required aggressive parenteral treatment. DISCUSSION: 
      Clonidine is an alpha-2 agonist with a nearly 100% bioavailability after oral or
      rectal administration. With high plasma concentration secondary to massive
      systemic overdose, the specificity for the alpha-2 receptor is lost and an alpha
      1 agonist activity predominates and causes marked hypertension. Management of
      clonidine overdose consists of supportive therapy guided by signs and symptoms.
      CONCLUSION:   Inadvertent injection into the subcutaneous pocket rather than the
      reservoir is rare but very dangerous as the drug cannot be retrieved and massive
      doses are involved. Signs and symptoms of systemic overdose with drugs commonly
      used in implanted drugs delivery system should be well known to ensure early
      diagnosis and treatment.

PMID- 21943356
TI  - Data-driven modelling of receptor tyrosine kinase signalling networks quantifies
      receptor-specific potencies of PI3K- and Ras-dependent ERK activation.
AB  - Signal transduction networks in mammalian cells, comprising a limited set of
      interacting biochemical pathways, are accessed by various growth factor and
      cytokine receptors to elicit distinct cell responses. This raises the question as
      to how specificity of the stimulus-response relationship is encoded at the
      molecular level. It has been proposed that specificity arises not only from the
      activation of unique signalling pathways, but also from quantitative differences
      in the activation and regulation of shared receptor-proximal signalling proteins.
      To address such hypotheses, data sets with greater precision and coverage of
      experimental conditions will need to be acquired, and rigorous frameworks that
      codify and parameterize the inherently non-linear relationships among signalling
      activities will need to be developed. In the present study we apply a systematic
      approach combining quantitative measurements and mathematical modelling to
      compare the signalling networks accessed by FGF (fibroblast growth factor) and
      PDGF (platelet-derived growth factor) receptors in mouse fibroblasts, in which
      the ERK (extracellular-signal-regulated kinase) cascade is activated by Ras- and
      PI3K (phosphoinositide 3-kinase)-dependent pathways. We show that, whereas the
      FGF stimulation of PI3K signalling is relatively weak, this deficiency is
      compensated for by a more potent Ras-dependent activation of ERK. Thus, as the
      modelling would predict, the ERK pathway is activated to a greater extent in
      cells co-stimulated with FGF and PDGF, relative to the saturated levels achieved
      with either ligand alone. It is envisaged that similar approaches will prove
      valuable in the elucidation of quantitative differences among other closely
      related receptor signalling networks.

PMID- 21943357
TI  - The intake of high fat diet with different trans fatty acid levels differentially
      induces oxidative stress and non alcoholic fatty liver disease (NAFLD) in rats.
AB  - BACKGROUND: Trans-fatty acids (TFA) are known as a risk factor for coronary
      artery diseases, insulin resistance and obesity accompanied by systemic
      inflammation, the features of metabolic syndrome. Little is known about the
      effects on the liver induced by lipids and also few studies are focused on the
      effect of foods rich in TFAs on hepatic functions and oxidative stress. This
      study investigates whether high-fat diets with different TFA levels induce
      oxidative stress and liver dysfunction in rats. METHODS: Male Wistar rats were
      divided randomly into four groups (n = 12/group): C receiving standard-chow;
      Experimental groups that were fed high-fat diet included 20% fresh soybean oil
      diet (FSO), 20% oxidized soybean oil diet (OSO) and 20% margarine diet (MG). Each
      group was kept on the treatment for 4 weeks. RESULTS: A liver damage was observed
      in rats fed with high-fat diet via increase of liver lipid peroxidation and
      decreased hepatic antioxidant enzyme activities (superoxide dismutase, catalase
      and glutathione peroxidase). The intake of oxidized oil led to higher levels of
      lipid peroxidation and a lower concentration of plasma antioxidants in comparison
      to rats fed with FSO. The higher inflammatory response in the liver was induced
      by MG diet. Liver histopathology from OSO and MG groups showed respectively
      moderate to severe cytoplasm vacuolation, hypatocyte hypertrophy, hepatocyte
      ballooning, and necroinflammation. CONCLUSION: It seems that a strong
      relationship exists between the consumption of TFA in the oxidized oils and lipid
      peroxidation and non alcoholic fatty liver disease (NAFLD). The extent of the
      peroxidative events in liver was also different depending on the fat source
      suggesting that feeding margarine with higher TFA levels may represent a direct
      source of oxidative stress for the organism. The present study provides evidence
      for a direct effect of TFA on NAFLD.

PMID- 21943358
TI  - How yeast re-programmes its transcriptional profile in response to different
      nutrient impulses.
AB  - BACKGROUND: A microorganism is able to adapt to changes in its physicochemical or
      nutritional environment and this is crucial for its survival. The yeast,
      Saccharomyces cerevisiae, has developed mechanisms to respond to such
      environmental changes in a rapid and effective manner; such responses may demand
      a widespread re-programming of gene activity. The dynamics of the re-organization
      of the cellular activities of S. cerevisiae in response to the sudden and
      transient removal of either carbon or nitrogen limitation has been studied by
      following both the short- and long-term changes in yeast's transcriptomic
      profiles. RESULTS: The study, which spans timescales from seconds to hours, has
      revealed the hierarchy of metabolic and genetic regulatory switches that allow
      yeast to adapt to, and recover from, a pulse of a previously limiting nutrient.
      At the transcriptome level, a glucose impulse evoked significant changes in the
      expression of genes concerned with glycolysis, carboxylic acid metabolism,
      oxidative phosphorylation, and nucleic acid and sulphur metabolism. In ammonium
      limited cultures, an ammonium impulse resulted in the significant changes in the
      expression of genes involved in nitrogen metabolism and ion transport. Although
      both perturbations evoked significant changes in the expression of genes involved
      in the machinery and process of protein synthesis, the transcriptomic response
      was delayed and less complex in the case of an ammonium impulse. Analysis of the
      regulatory events by two different system-level, network-based approaches
      provided further information about dynamic organization of yeast cells as a
      response to a nutritional change. CONCLUSIONS: The study provided important
      information on the temporal organization of transcriptomic organization and
      underlying regulatory events as a response to both carbon and nitrogen impulse.
      It has also revealed the importance of a long-term dynamic analysis of the
      response to the relaxation of a nutritional limitation to understand the
      molecular basis of the cells' dynamic behaviour.

PMID- 21943359
TI  - Perceptions of the Muslim religious leaders and their attitudes on herbal
      medicine in Bangladesh: a cross-sectional study.
AB  - BACKGROUND: Herbal Medicines (HMs) are playing major roles in the health of the
      millions of people worldwide. Muslim Religious Leader (MRLs), being an important
      component of the society with huge influence on it, could contribute a lot to
      promote HM. This study was aimed at evaluating perceptions of the MRLs, their
      satisfaction and attitudes towards HM in Bangladesh. METHODS: This cross
      sectional study collected data from a purposive sample of 503 MRLs using an
      interviewer-administered structured questionnaire during December 2010 and
      January 2011. Main outcome measures included sociodemographic variables, MRLs'
      preferences in using HMs, their satisfaction and intent to use HMs in the future,
      and finally MRLs' attitudes toward HM use. RESULTS: Although two-fifth (40.4%) of
      the MRLs preferred HM among different form of complementary and alternative
      medicines, they used orthodox medicine (OM) more frequently than HM in last one
      year. Majority believed that HM was effective for all age groups (52.6%) and both
      sexes (74.5%). One-third felt that HM was more effective for chronic diseases,
      68.5% felt that it only promotes health, and 40.8% said it keeps them relaxed.
      About 98.0% of the respondents experienced 'no harm' but 'benefit' from HM;
      naturally, they were satisfied with HM and were willing to recommend it to
      others. Urban, older (>40 years), and 'single' respondents were more likely to
      use HM (gender and education adjusted odds ratios = 1.7 [95% confidence interval,
      CI = 1.1-2.6], 1.9 [95% CI = 1.3-3.0], and 1.6 [95% CI = 1.2-2.1], respectively).
      Overall, respondents exhibited very positive attitude towards HM with mean score
      of 4.2 (range, 3.7-4.6) of a 5-point Likert scale (Score 5 for strongly agree to
      1 for strongly disagree). CONCLUSIONS: We report adequate perceptions,
      satisfaction, and very positive attitudes towards HM among MRLs. Mass media had a
      significant contribution towards its promotion. If HM are to assume a respected
      place in the contemporary healthcare, its acceptance among general population
      needs to be established through incorporating MRLs in the process of HM promotion
      in Bangladesh.

PMID- 21943360
TI  - Granulocyte colony-stimulating factors for febrile neutropenia prophylaxis
      following chemotherapy: systematic review and meta-analysis.
AB  - BACKGROUND: Febrile neutropenia (FN) occurs following myelosuppressive
      chemotherapy and is associated with morbidity, mortality, costs, and chemotherapy
      reductions and delays. Granulocyte colony-stimulating factors (G-CSFs) stimulate
      neutrophil production and may reduce FN incidence when given prophylactically
      following chemotherapy. METHODS: A systematic review and meta-analysis assessed
      the effectiveness of G-CSFs (pegfilgrastim, filgrastim or lenograstim) in
      reducing FN incidence in adults undergoing chemotherapy for solid tumours or
      lymphoma. G-CSFs were compared with no primary G-CSF prophylaxis and with one
      another. Nine databases were searched in December 2009. Meta-analysis used a
      random effects model due to heterogeneity. RESULTS: Twenty studies compared
      primary G-CSF prophylaxis with no primary G-CSF prophylaxis: five studies of
      pegfilgrastim; ten of filgrastim; and five of lenograstim. All three G-CSFs
      significantly reduced FN incidence, with relative risks of 0.30 (95% CI: 0.14 to
      0.65) for pegfilgrastim, 0.57 (95% CI: 0.48 to 0.69) for filgrastim, and 0.62
      (95% CI: 0.44 to 0.88) for lenograstim. Overall, the relative risk of FN for any
      primary G-CSF prophylaxis versus no primary G-CSF prophylaxis was 0.51 (95% CI:
      0.41 to 0.62). In terms of comparisons between different G-CSFs, five studies
      compared pegfilgrastim with filgrastim. FN incidence was significantly lower for
      pegfilgrastim than filgrastim, with a relative risk of 0.66 (95% CI: 0.44 to
      0.98). CONCLUSIONS: Primary prophylaxis with G-CSFs significantly reduces FN
      incidence in adults undergoing chemotherapy for solid tumours or lymphoma.
      Pegfilgrastim reduces FN incidence to a significantly greater extent than
      filgrastim.

PMID- 21943361
TI  - The influence of maternal Lewis, Secretor and ABO(H) blood groups on fetal growth
      restriction.
AB  - BACKGROUND: Fetal growth restriction (FGR) is associated with thrombosis of the
      placenta and an increased risk of subsequent vascular disease in the mother and
      fetus. The products of interactions between ABO(H), Lewis and Secretor genes are
      also associated with thrombosis and vascular disease risk. OBJECTIVES/METHODS: A
      prospective case-control study of mothers with a severe FGR pregnancy (cases, n =
      128; controls, n = 288) was performed to determine whether FGR is associated with
      particular maternal blood groups. RESULTS: No association with ABO(H) status was
      observed, but FGR was more common in maternal secretors (odds ratio [OR] 1.70,
      95% confidence interval [CI] 1.08-2.69) and consequently in those mothers
      expressing Le(b) on their red cells (OR 1.80, 95% CI 1.15-2.83), with a reduced
      risk in non-secretors and those expressing Le(a). Given the association between
      blood groups and both activated protein C resistance (APCR) and von Willebrand
      factor (VWF) levels, post hoc pilot studies on first-trimester APCR and VWF
      antigen levels and blood group genotypes were performed. No relationship with
      Lewis or Secretor was observed. Despite this, lower first-trimester VWF levels
      were observed in pregnancies subsequently complicated by FGR. CONCLUSIONS:  This
      is the first study reporting a relationship between maternal Secretor/Lewis
      status and FGR. A link between blood groups and FGR is plausible, as both are
      associated with cardiovascular disease. We observed no relationship between
      Lewis/Secretor status and VWF or APCR, but this should be confirmed in a larger
      study. Thus, the mechanism whereby Secretor and/or Lewis influences FGR is
      unknown.

PMID- 21943362
TI  - Genome wide gene expression regulation by HIP1 Protein Interactor, HIPPI:
      prediction and validation.
AB  - BACKGROUND: HIP1 Protein Interactor (HIPPI) is a pro-apoptotic protein that
      induces Caspase8 mediated apoptosis in cell. We have shown earlier that HIPPI
      could interact with a specific 9 bp sequence motif, defined as the HIPPI binding
      site (HBS), present in the upstream promoter of Caspase1 gene and regulate its
      expression. We also have shown that HIPPI, without any known nuclear localization
      signal, could be transported to the nucleus by HIP1, a NLS containing nucleo
      cytoplasmic shuttling protein. Thus our present work aims at the investigation of
      the role of HIPPI as a global transcription regulator. RESULTS: We carried out
      genome wide search for the presence of HBS in the upstream sequences of genes.
      Our result suggests that HBS was predominantly located within 2 Kb upstream from
      transcription start site. Transcription factors like CREBP1, TBP, OCT1, EVI1 and
      P53 half site were significantly enriched in the 100 bp vicinity of HBS
      indicating that they might co-operate with HIPPI for transcription regulation. To
      illustrate the role of HIPPI on transcriptome, we performed gene expression
      profiling by microarray. Exogenous expression of HIPPI in HeLa cells resulted in
      up-regulation of 580 genes (p < 0.05) while 457 genes were down-regulated.
      Several transcription factors including CBP, REST, C/EBP beta were altered by
      HIPPI in this study. HIPPI also interacted with P53 in the protein level. This
      interaction occurred exclusively in the nuclear compartment and was absent in
      cells where HIP1 was knocked down. HIPPI-P53 interaction was necessary for HIPPI
      mediated up-regulation of Caspase1 gene. Finally, we analyzed published
      microarray data obtained with post mortem brains of Huntington's disease (HD)
      patients to investigate the possible involvement of HIPPI in HD pathogenesis. We
      observed that along with the transcription factors like CREB, P300, SREBP1, Sp1
      etc. which are already known to be involved in HD, HIPPI binding site was also
      significantly over-represented in the upstream sequences of genes altered in HD.
      CONCLUSIONS: Taken together, the results suggest that HIPPI could act as an
      important transcription regulator in cell regulating a vast array of genes,
      particularly transcription factors and at least, in part, play a role in
      transcription deregulation observed in HD.

PMID- 21943363
TI  - The relative efficacy of nine osteoporosis medications for reducing the rate of
      fractures in post-menopausal women.
AB  - BACKGROUND: In the absence of head-to-head trials, indirect comparisons of
      randomized placebo-controlled trials may provide a viable option to assess
      relative efficacy. The purpose was to estimate the relative efficacy of reduction
      of fractures in post-menopausal women, and to assess robustness of the results.
      METHODS: A systematic literature review of multiple databases identified
      randomized placebo-controlled trials with nine drugs for post-menopausal women.
      Odds ratio and 95% credibility intervals for the rates of hip, non-vertebral,
      vertebral, and wrist fractures for each drug and between drugs were derived using
      a Bayesian approach. A drug was ranked as the most efficacious if it had the
      highest posterior odds ratio, or had the highest effect size. RESULTS: 30 studies
      including 59,209 patients reported fracture rates for nine drugs: alendronate (6
      studies), denosumab (1 study), etidronate (8 studies), ibandronate (4 studies),
      raloxifene (1 study), risedronate (7 studies), strontium (2 study), teriparatide
      (1 study), and zoledronic acid (1 study). The drugs with the highest probability
      of reducing non-vertebral fractures was etidronate and teriparatide while the
      drugs with the highest probability of reducing vertebral, hip or wrist fractures
      were teriparatide, zoledronic acid and denosumab. The drugs with the largest
      effect size for vertebral fractures were zoledronic acid, teriparatide and
      denosumab, while the drugs with the highest effect size for non-vertebral, hip or
      wrist fractures were alendronate or risedronate. Estimates were consistent
      between Bayesian and classical approaches. CONCLUSION: Teriparatide, zoledronic
      acid and denosumab have the highest probabilities of being most efficacious for
      non-vertebral and vertebral fractures, and having the greatest effect sizes. The
      estimates from indirect comparisons were robust to differences in methodology.

PMID- 21943364
TI  - The effects of spherical aberration on static accommodative responses in
      emmetropes and myopes.
AB  - PURPOSE: To compare the effects of spherical aberration (SA) on accommodative
      responses between emmetropes (EMs), stable myopes (SMs), and progressing myopes
      (PMs). METHODS: The accommodative responses (AR) induced by negative lenses from
      0 to -5 D in 1 D steps were measured with a Complete Ophthalmic Analysis System
      (COAS) for 10 emmetropes (EMs), 13 stable myopes (SMs), and 9 progressing myopes
      (PMs). Three types of AR were calculated from wavefront aberration data based on
      ocular foci within a paraxial area, natural pupil area, and a 3.5 mm-diameter
      annular pupil area. The accommodative stimulus response curves (ASRCs) were
      compared between the three groups and between the three AR conditions. RESULTS:
      The difference in the slope of ASRC was significant between the three AR
      conditions (p < 0.0001) but it was not significant between the three refractive
      groups. In each group, the slope of ASRC for the accommodative response measured
      within the paraxial area of the pupil (paraxial AR) was significantly steeper
      than that measured for the natural pupil (total AR) and also for that estimated
      for the 3.5 mm-diameter annular pupil (p < 0.01). The difference in the y
      intercept of ASRC between the three AR conditions was also significant (p = 0.02)
      but not between the three refractive groups. The y-intercept of ASRC for paraxial
      AR was more positive than that for total AR in SMs (p < 0.01) and in PMs (p <
      0.05); the y-intercept of ASRC for the 3.5 mm peripheral AR was more positive
      than that for total AR in SMs (p < 0.05). CONCLUSIONS: The spherical aberration
      of the eye has a significant effect on the slope of ASRC and is less in PMs than
      in EMs and SMs.

PMID- 21943365
TI  - Narrow-band imaging does not improve detection of colorectal polyps when compared
      to conventional colonoscopy: a randomized controlled trial and meta-analysis of
      published studies.
AB  - BACKGROUND: A colonoscopy may frequently miss polyps and cancers. A number of
      techniques have emerged to improve visualization and to reduce the rate of
      adenoma miss. METHODS: We conducted a randomized controlled trial (RCT) in two
      clinics of the Gastrointestinal Department of the Sanitas University Foundation
      in Bogota, Colombia. Eligible adult patients presenting for screening or
      diagnostic elective colonoscopy were randomly allocated to undergo conventional
      colonoscopy or narrow-band imaging (NBI) during instrument withdrawal by three
      experienced endoscopists. For the systematic review, studies were identified from
      the Cochrane Library, PUBMED and LILACS and assessed using the Cochrane risk of
      bias tool. RESULTS: We enrolled a total of 482 patients (62.5% female), with a
      mean age of 58.33 years (SD 12.91); 241 into the intervention (NBI) colonoscopy
      and 241 into the conventional colonoscopy group. Most patients presented for
      diagnostic colonoscopy (75.3%). The overall rate of polyp detection was
      significantly higher in the conventional group compared to the NBI group (RR
      0.75, 95%CI 0.60 to 0.96). However, no significant differences were found in the
      mean number of polyps (MD -0.1; 95%CI -0.25 to 0.05), and the mean number of
      adenomas (MD 0.04 95%CI -0.09 to 0.17). Meta-analysis of studies (regardless of
      indication) did not find any significant differences in the mean number of polyps
      (5 RCT, 2479 participants; WMD -0.07 95% CI -0.21 to 0.07; I2 68%), the mean
      number of adenomas (8 RCT, 3517 participants; WMD -0.08 95% CI -0.17; 0.01 to I2
      62%) and the rate of patients with at least one adenoma (8 RCT, 3512
      participants, RR 0.96 95% CI 0.88 to 1,04;I2 0%). CONCLUSION: NBI does not
      improve detection of colorectal polyps when compared to conventional colonoscopy
      (Australian New Zealand Clinical Trials Registry ACTRN12610000456055).

PMID- 21943366
TI  - Multidetector-row computed tomography of thoracic aortic anomalies in dogs and
      cats: patent ductus arteriosus and vascular rings.
AB  - BACKGROUND: Diagnosis of extracardiac intrathoracic vascular anomalies is of
      clinical importance, but remains challenging. Traditional imaging modalities,
      such as radiography, echocardiography, and angiography, are inherently limited by
      the difficulties of a 2-dimensional approach to a 3-dimensional object. We
      postulated that accurate characterization of malformations of the aorta would
      benefit from 3-dimensional assessment. Therefore, multidetector-row computed
      tomography (MDCT) was chosen as a 3-dimensional, new, and noninvasive imaging
      technique. The purpose of this study was to evaluate patients with 2 common
      diseases of the intrathoracic aorta, either patent ductus arteriosus or vascular
      ring anomaly, by contrast-enhanced 64-row computed tomography. RESULTS:
      Electrocardiography (ECG)-gated and thoracic nongated MDCT images were reviewed
      in identified cases of either a patent ductus arteriosus or vascular ring
      anomaly. Ductal size and morphology were determined in 6 dogs that underwent ECG
      gated MDCT. Vascular ring anomalies were characterized in 7 dogs and 3 cats by
      ECG-gated MDCT or by a nongated thoracic standard protocol. Cardiac ECG-gated
      MDCT clearly displayed the morphology, length, and caliber of the patent ductus
      arteriosus in 6 affected dogs. Persistent right aortic arch was identified in 10
      animals, 8 of which showed a coexisting aberrant left subclavian artery. A mild
      dilation of the proximal portion of the aberrant subclavian artery near its
      origin of the aorta was present in 4 dogs, and a diverticulum analogous to the
      human Kommerell's diverticulum was present in 2 cats. CONCLUSIONS: Contrast
      enhanced MDCT imaging of thoracic anomalies gives valuable information about the
      exact aortic arch configuration. Furthermore, MDCT was able to characterize the
      vascular branching patterns in dogs and cats with a persistent right aortic arch
      and the morphology and size of the patent ductus arteriosus in affected dogs.
      This additional information can be of help with regard to improved diagnoses of
      thoracic anomalies and the planning of surgical interventions.

PMID- 21943367
TI  - iCTNet: a Cytoscape plugin to produce and analyze integrative complex traits
      networks.
AB  - BACKGROUND: The speed at which biological datasets are being accumulated stands
      in contrast to our ability to integrate them meaningfully. Large-scale biological
      databases containing datasets of genes, proteins, cells, organs, and diseases are
      being created but they are not connected. Integration of these vast but
      heterogeneous sources of information will allow the systematic and comprehensive
      analysis of molecular and clinical datasets, spanning hundreds of dimensions and
      thousands of individuals. This integration is essential to capitalize on the
      value of current and future molecular- and cellular-level data on humans to gain
      novel insights about health and disease. RESULTS: We describe a new open-source
      Cytoscape plugin named iCTNet (integrated Complex Traits Networks). iCTNet
      integrates several data sources to allow automated and systematic creation of
      networks with up to five layers of omics information: phenotype-SNP association,
      protein-protein interaction, disease-tissue, tissue-gene, and drug-gene
      relationships. It facilitates the generation of general or specific network views
      with diverse options for more than 200 diseases. Built-in tools are provided to
      prioritize candidate genes and create modules of specific phenotypes.
      CONCLUSIONS: iCTNet provides a user-friendly interface to search, integrate,
      visualize, and analyze genome-scale biological networks for human complex traits.
      We argue this tool is a key instrument that facilitates systematic integration of
      disparate large-scale data through network visualization, ultimately allowing the
      identification of disease similarities and the design of novel therapeutic
      approaches.The online database and Cytoscape plugin are freely available for
      academic use at: http://www.cs.queensu.ca/ictnet.

PMID- 21943368
TI  - Impact of traumatic dental injuries and malocclusions on quality of life of young
      children.
AB  - BACKGROUND: The presence of traumatic dental injuries and malocclusions can have
      a negative impact on quality of life of young children and their parents,
      affecting their oral health and well-being. The aim of this study was to assess
      the impact of traumatic dental injuries and anterior malocclusion traits on the
      Oral Health-Related Quality of Life (OHRQoL) of children between 2 and 5 years
      old. METHODS: Parents of 260 children answered the six domains of the Early
      Childhood Oral Health Impact Scale (ECOHIS) on their perception of the OHRQoL
      (outcome). Two calibrated dentists assessed the types of traumatic dental
      injuries (Kappa = 0.9) and the presence of anterior malocclusion traits (Kappa =
      1.0). OHRQoL was measured using the ECOHIS. Poisson regression was used to
      associate the type of traumatic dental injury and the presence of anterior
      malocclusion traits to the outcome. RESULTS: The presence of anterior
      malocclusion traits did not show a negative impact on the overall OHRQoL mean or
      in each domain. Only complicated traumatic dental injuries showed a negative
      impact on the symptoms (p = 0.005), psychological (p = 0.029), self image/social
      interaction (p = 0.004) and family function (p = 0.018) domains and on the
      overall OHRQoL mean score (p = 0.002). The presence of complicated traumatic
      dental injuries showed an increased negative impact on the children's quality of
      life (RR = 1.89; 95% CI = 1.36, 2.63; p < 0.001). CONCLUSIONS: Complicated
      traumatic dental injuries have a negative impact on the OHRQoL of preschool
      children and their parents, but anterior malocclusion traits do not.

PMID- 21943369
TI  - Reading and writing difficulties in adolescence and later risk of welfare
      dependence. A ten year follow-up, the HUNT Study, Norway.
AB  - BACKGROUND: Welfare dependence and low work participation among young people have
      raised concern in many European countries. Reading and writing difficulties (RWD)
      might make young people vulnerable to work integration problems and welfare
      dependence through negative influences on education and health. Our main
      objective of this study was to examine if RWD in adolescence affected the risk of
      welfare dependence in young adulthood. METHODS: Baseline information on self
      reported RWD, health and family was obtained for 8950 school-attending
      adolescents in Nord-Trondelag County, Norway, participating in the Young-HUNT1
      survey, 1995-97. All individuals were linked to biological parents to identify
      siblings and parental education from national registers. Welfare dependence was
      assessed by the reception of social benefits (medical and economic) from the
      national social insurance database (1998-2007). Only long-term benefits (> 180
      days) were included. RESULTS: The adolescents who reported RWD at baseline were
      more likely to receive medical or social benefits during follow-up compared with
      those who did not report RWD. In girls with RWD, the adjusted 5-year risk (at age
      24 to 28) for receiving medical benefits was 0.20 (95% confidence interval 0.14
      0.26), compared with 0.11 (0.09-0.12) in girls without RWD. In boys the
      corresponding risks were 0.13 (0.09-0.17) and 0.08 (0.07-0.09). CONCLUSIONS: The
      associations between RWD in adolescence and welfare dependence later in life
      suggest that increased attention should be paid to these problems when discussing
      the public health aspects of work integration, since there might be a potential
      for prevention.

PMID- 21943370
TI  - A computational model study of the influence of the anatomy of the circle of
      willis on cerebral hyperperfusion following carotid artery surgery.
AB  - BACKGROUND: Cerebral hyperperfusion syndrome develops in a small subset of
      patients following carotid artery surgery (CAS) performed to treat severe carotid
      artery stenosis. This syndrome has been found to have a close correlation with
      cerebral hyperperfusion occurring after CAS. The purpose of this study is to
      investigate whether and how the anatomy of the Circle of Willis (CoW) of the
      cerebral circulation influences post-CAS cerebral hyperperfusion. METHODS: A
      computational model of the cerebral circulation coupled with the global
      cardiovascular system has been developed to investigate hemodynamic events
      associated with CAS. Nine topological structures of the CoW were investigated in
      combination with various distribution patterns of stenosis in the feeding
      arteries of the cerebral circulation. RESULTS: The occurrence of post-CAS
      cerebral hyperperfusion was predicted for the CoW structures that have poor
      collateral pathways between the stenosed cerebral feeding arteries and the
      remaining normal feeding arteries. The risk and the localization of post-CAS
      hyperperfusion were determined jointly by the anatomy of the CoW and the
      distribution pattern of stenosis in the cerebral feeding arteries. The presence
      of basilar artery stenosis or contralateral ICA stenosis increased the risk of
      post-CAS hyperperfusion and enlarged the cerebral region affected by
      hyperperfusion. For a certain CoW structure, the diameters of the cerebral
      communicating arteries and the severity of carotid artery stenosis both had a
      significant influence on the computed post-CAS cerebral hyperperfusion rates.
      Moreover, post-CAS cerebral hyperperfusion was predicted to be accompanied with
      an excessively high capillary transmural pressure. CONCLUSIONS: This study
      demonstrated the importance of considering the anatomy of the CoW in assessing
      the risk of post-CAS cerebral hyperperfusion. Particularly, since the anatomy of
      the CoW and the distribution pattern of stenosis in the cerebral feeding arteries
      jointly determine the risk and localization of post-CAS cerebral hyperperfusion,
      a patient-specific hemodynamic analysis aimed to help physicians identify
      patients at high risk of cerebral hyperperfusion should account for the combined
      effect of the anatomy of cerebral arteries and cerebral feeding artery stenoses
      on cerebral hemodynamics.

PMID- 21943371
TI  - Secondary uses and the governance of de-identified data: lessons from the human
      genome diversity panel.
AB  - BACKGROUND: Recent changes to regulatory guidance in the US and Europe have
      complicated oversight of secondary research by rendering most uses of de
      identified data exempt from human subjects oversight. To identify the
      implications of such guidelines for harms to participants and communities, this
      paper explores the secondary uses of one de-identified DNA sample collection with
      limited oversight: the Human Genome Diversity Project (HGDP)-Centre d'Etude du
      Polymorphisme Humain, Fondation Jean Dausset (CEPH) Human Genome Diversity Panel.
      METHODS: Using a combination of keyword and cited reference search, we identified
      English-language scientific articles published between 2002 and 2009 that
      reported analysis of HGDP Diversity Panel samples and/or data. We then reviewed
      each article to identify the specific research use to which the samples and/or
      data was applied. Secondary uses were categorized according to the type and kind
      of research supported by the collection. RESULTS: A wide variety of secondary
      uses were identified from 148 peer-reviewed articles. While the vast majority of
      these uses were consistent with the original intent of the collection, a minority
      of published reports described research whose primary findings could be regarded
      as controversial, objectionable, or potentially stigmatizing in their
      interpretation. CONCLUSIONS: We conclude that potential risks to participants and
      communities cannot be wholly eliminated by anonymization of individual data and
      suggest that explicit review of proposed secondary uses, by a Data Access
      Committee or similar internal oversight body with suitable stakeholder
      representation, should be a required component of the trustworthy governance of
      any repository of data or specimens.

PMID- 21943372
TI  - In vivo kinetics of transcription initiation of the lar promoter in Escherichia
      coli. Evidence for a sequential mechanism with two rate-limiting steps.
AB  - BACKGROUND: In Escherichia coli the mean and cell-to-cell diversity in RNA
      numbers of different genes vary widely. This is likely due to different kinetics
      of transcription initiation, a complex process with multiple rate-limiting steps
      that affect RNA production. RESULTS: We measured the in vivo kinetics of
      production of individual RNA molecules under the control of the lar promoter in
      E. coli. From the analysis of the distributions of intervals between
      transcription events in the regimes of weak and medium induction, we find that
      the process of transcription initiation of this promoter involves a sequential
      mechanism with two main rate-limiting steps, each lasting hundreds of seconds.
      Both steps become faster with increasing induction by IPTG and Arabinose.
      CONCLUSIONS: The two rate-limiting steps in initiation are found to be important
      regulators of the dynamics of RNA production under the control of the lar
      promoter in the regimes of weak and medium induction. Variability in the
      intervals between consecutive RNA productions is much lower than if there was
      only one rate-limiting step with a duration following an exponential
      distribution. The methodology proposed here to analyze the in vivo dynamics of
      transcription may be applicable at a genome-wide scale and provide valuable
      insight into the dynamics of prokaryotic genetic networks.

PMID- 21943373
TI  - Exercise prior to a freely requested meal modifies pre and postprandial glucose
      profile, substrate oxidation and sympathovagal balance.
AB  - BACKGROUND: The effects of exercise on glucose and metabolic events preceding and
      following a freely initiated meal have never been assessed. Moreover, the
      relationship between these events and sympathovagal balance is not known. The
      objective of this study was to determine whether exercise prior to a freely
      requested meal modifies the pre- and postprandial glucose profile, substrate
      oxidation and sympathovagal balance. METHODS: Nine young active male subjects
      consumed a standard breakfast (2298 +/- 357 kJ). After 120 min, they either
      performed 75 min of exercise on a cycle ergometer (EX - 70% VO2max) or rested
      (RT). Lunch was freely requested but eaten ad libitum only during the 1st
      session, and then energy intake was fixed across conditions. Glucose and
      sympathovagal balance were assessed continuously using a subcutaneous glucose
      monitoring system and analysis of heart rate variability, respectively. Every 5
      min, a mean value was calculated for both glucose and sympathovagal balance.
      Substrate oxidation was determined by calculating the gas exchange ratio when
      lunch was requested and 180 min after the onset of eating. RESULTS: Preprandial
      glucose profiles were found in 72% of the sessions and with a similar frequency
      under both conditions. Meals were requested after a similar delay (40 +/- 12 and
      54 +/- 10 min in EX and RT respectively; ns). At meal request, sympathovagal
      balance was not different between conditions but CHO oxidation was lower and fat
      oxidation higher in EX than in RT (-46% and +63%, respectively; both p < 0.05).
      Glucose responses to the meal were higher in incremental (+ 48%) but not in
      absolute value in EX than in RT, with a higher fat oxidation (+ 46%, p < 0.05),
      and a greater vagal withdrawal (+ 15%, p < 0.05). CONCLUSIONS: These results show
      that exercise does not impair preprandial glucose declines at the following meal
      freely requested, but leads to an increased postprandial glucose response and an
      elevated fat oxidation, an effect that vagal withdrawal may contribute to
      explain.

PMID- 21943374
TI  - Iron-mediated retinal degeneration in haemojuvelin-knockout mice.
AB  - Haemochromatosis is a genetic disorder of iron overload resulting from loss-of
      function mutations in genes coding for the iron-regulatory proteins HFE (human
      leucocyte antigen-like protein involved in iron homoeostasis), transferrin
      receptor 2, ferroportin, hepcidin and HJV (haemojuvelin). Recent studies have
      established the expression of all of the five genes in the retina, indicating
      their importance in retinal iron homoeostasis. Previously, we demonstrated that
      HJV is expressed in RPE (retinal pigment epithelium), the outer and inner nuclear
      layers and the ganglion cell layer. In the present paper, we report on the
      consequences of Hjv deletion on the retina in mice. Hjv-/- mice at >=18 months of
      age had increased iron accumulation in the retina with marked morphological
      damage compared with age-matched controls; these changes were not found in
      younger mice. The retinal phenotype in Hjv-/- mice included hyperplasia of RPE.
      We isolated RPE cells from wild-type and Hjv-/- mice and examined their growth
      patterns. Hjv-/- RPE cells were less senescent and exhibited a hyperproliferative
      phenotype. Hjv-/- RPE cells also showed up-regulation of Slc7a11 (solute carrier
      family 7 member 11 gene), which encodes the 'transporter proper' subunit xCT in
      the heterodimeric amino acid transporter xCT/4F2hc (cystine/glutamate exchanger).
      BMP6 (bone morphogenetic protein 6) could not induce hepcidin expression in Hjv-/
      RPE cells, confirming that retinal cells require HJV for induction of hepcidin
      via BMP6 signalling. HJV is a glycosylphosphatidylinositol-anchored protein, and
      the membrane-associated HJV is necessary for BMP6-mediated activation of hepcidin
      promoter in RPE cells. Taken together, these results confirm the biological
      importance of HJV in the regulation of iron homoeostasis in the retina and in
      RPE.

PMID- 21943376
TI  - Subcutaneous stimulation as an additional therapy to spinal cord stimulation for
      the treatment of lower limb pain and/or back pain: a feasibility study.
AB  - OBJECTIVE: The objective of this study was to demonstrate the efficacy of
      subcutaneous stimulation (SubQ) as an additional therapy in patients with failed
      back surgery syndrome (FBSS) with chronic refractory pain, for whom spinal cord
      stimulation (SCS) was unsuccessful in treating low back pain. STUDY DESIGN: Case
      series. MATERIALS AND METHODS: FBSS patients with chronic limb and/or low back
      pain whose conventional therapies had failed received a combination of SCS (8
      contact Octad lead) and/or SubQ (4-contact Quad Plus lead(s)). Initially leads
      were placed in the epidural space for SCS for a trial stimulation to assess
      response to suppression of limb and low back pain. Where SCS alone was
      insufficient in treating lower back pain, leads were placed superficially in the
      subcutaneous tissue of the lower back, directly in the middle of the pain area. A
      pulse generator was implanted if patients reported more than 50% pain relief
      during the trial period. Pain intensity for limb and lower back pain was scored
      separately, using visual analog scale (VAS). Pain and Quebec Back Pain Disability
      Scale (QBPDS) after 12-month treatment were compared with pain and QBPDS at
      baseline. RESULTS: Eleven FBSS patients, five male and six female (age: 51 +/- 8
      years; mean +/- SD), in whom SCS alone was insufficient in treating lower back
      pain, were included. In nine cases, SubQ was used in combination with SCS to
      treat chronic lower back and lower extremity pain. In two cases only SubQ was
      used to treat lower back pain. SCS significantly reduced limb pain after 12
      months (VAS(bl) : 62 +/- 14 vs. VAS(12m) : 20 +/- 11; p= 0.001, N= 8). SubQ
      stimulation significantly reduced low back pain after 12 months (VAS(bl) : 62 +/-
      13.0 vs. VAS(12m) : 32 +/- 16; p= 0.0002, N= 10). Overall pain medication was
      reduced by more than 70%. QBPDS improved from 61 +/- 15 to 49 +/- 12 (p= 0.046,
      N= 10). Furthermore, we observed that two patients returned to work. CONCLUSION:
      SubQ may be an effective additional treatment for chronic low back pain in
      patients with FBSS for whom SCS alone is insufficient in alleviating their pain
      symptoms.

PMID- 21943375
TI  - Reptilian-transcriptome v1.0, a glimpse in the brain transcriptome of five
      divergent Sauropsida lineages and the phylogenetic position of turtles.
AB  - BACKGROUND: Reptiles are largely under-represented in comparative genomics
      despite the fact that they are substantially more diverse in many respects than
      mammals. Given the high divergence of reptiles from classical model species, next
      generation sequencing of their transcriptomes is an approach of choice for gene
      identification and annotation. RESULTS: Here, we use 454 technology to sequence
      the brain transcriptome of four divergent reptilian and one reference avian
      species: the Nile crocodile, the corn snake, the bearded dragon, the red-eared
      turtle, and the chicken. Using an in-house pipeline for recursive similarity
      searches of >3,000,000 reads against multiple databases from 7 reference
      vertebrates, we compile a reptilian comparative transcriptomics dataset, with
      homology assignment for 20,000 to 31,000 transcripts per species and a cumulated
      non-redundant sequence length of 248.6 Mbases. Our approach identifies the
      majority (87%) of chicken brain transcripts and about 50% of de novo assembled
      reptilian transcripts. In addition to 57,502 microsatellite loci, we identify
      thousands of SNP and indel polymorphisms for population genetic and linkage
      analyses. We also build very large multiple alignments for Sauropsida and mammals
      (two million residues per species) and perform extensive phylogenetic analyses
      suggesting that turtles are not basal living reptiles but are rather associated
      with Archosaurians, hence, potentially answering a long-standing question in the
      phylogeny of Amniotes. CONCLUSIONS: The reptilian transcriptome (freely available
      at http://www.reptilian-transcriptomes.org) should prove a useful new resource as
      reptiles are becoming important new models for comparative genomics, ecology, and
      evolutionary developmental genetics.

PMID- 21943377
TI  - Relationship between daylength and suicide in Finland.
AB  - BACKGROUND: Many previous studies have documented seasonal variation in suicides
      globally. We re-assessed the seasonal variation of suicides in Finland and tried
      to relate it to the seasonal variation in daylength and ambient temperature and
      in the discrepancy between local time and solar time. METHODS: The daily data of
      all suicides from 1969 to 2003 in Finland (N = 43,393) were available. The
      calendar year was divided into twelve periods according to the length of daylight
      and the routinely changing time difference between sun time and official time.
      The daily mean of suicide mortality was calculated for each of these periods and
      the 95% confidence intervals of the daily means were used to evaluate the
      statistical significance of the means. In addition, daily changes in sunshine
      hours and mean temperature were compared to the daily means of suicide mortality
      in two locations during these afore mentioned periods. RESULTS: A significant
      peak of the daily mean value of suicide mortality occurred in Finland between May
      15th and July 25th, a period that lies symmetrically around the solstice.
      Concerning the suicide mortality among men in the northern location (Oulu), the
      peak was postponed as compared with the southern location (Helsinki). The daily
      variation in temperature or in sunshine did not have significant association with
      suicide mortality in these two locations. CONCLUSIONS: The period with the
      longest length of the day associated with the increased suicide mortality.
      Furthermore, since the peak of suicide mortality seems to manifest later during
      the year in the north, some other physical or biological signals, besides the
      variation in daylight, may be involved. In order to have novel means for suicide
      prevention, the assessment of susceptibility to the circadian misalignment might
      help.

PMID- 21943378
TI  - Whole-exome sequencing of DNA from peripheral blood mononuclear cells (PBMC) and
      EBV-transformed lymphocytes from the same donor.
AB  - BACKGROUND: The creation of lymphoblastoid cell lines (LCLs) through Epstein-Barr
      virus (EBV) transformation of B-lymphocytes can result in a valuable biomaterial
      for cell biology research and a renewable source of DNA. While LCLs have been
      used extensively in cellular and genetic studies, the process of cell
      transformation and expansion during culturing may introduce genomic changes that
      may impact their use and the interpretation of subsequent genetic findings.
      RESULTS: We performed whole exome sequencing on a tetrad family using DNA derived
      from peripheral blood mononuclear cells (PBMCs) and LCLs from each individual. We
      generated over 4.7 GB of mappable sequence to a 125X read coverage per sample. An
      average of 19,354 genetic variants were identified. Comparison of the two DNA
      sources from each individual showed an average concordance rate of 95.69%. By
      lowering the variant calling parameters, the concordance rate between the paired
      samples increased to 99.82%. Sanger sequencing of a subset of the remaining
      discordant variants did confirm the presence of de novo mutations arising in
      LCLs. CONCLUSIONS: By varying software stringency parameters, we identified 99%
      concordance between DNA sequences derived from the two different sources from the
      same donors. These results suggest that LCLs are an appropriate representation of
      the genetic material of the donor and suggest that EBV transformation can result
      in low-level generation of de novo mutations. Therefore, use of PBMC or early
      passage EBV-transformed cells is recommended. These findings have broad-reaching
      implications, as there are thousands of LCLs in public biorepositories and
      individual laboratories.

PMID- 21943379
TI  - Non-response in a survey of physicians on end-of-life care for the elderly.
AB  - BACKGROUND: Physicians are quite often surveyed with the aim to investigate their
      opinions regarding provision and improvement of health care. However, in many
      cases response rates tend to be rather low. The aim of the study is to reflect
      methodological aspects regarding survey conduction and to analyse factors that
      cause physicians to take part in a study on delivering end-of-life care for the
      elderly. METHODS: N = 4,727 physicians in Lower Saxony, Germany, received a
      standardised questionnaire on their attitudes about end-of-life care for the
      elderly. Non-responders were asked to state the reasons for non-participation.
      Comparison of the sociodemographic characteristics between responders and non
      responders, and evaluation of the reasons for non-participation were made.
      RESULTS: The response rate to the questionnaire on end-of-life care for the
      elderly was 40% (n = 1,892). Of the non-responders to the questionnaire, 12.8% (n
      = 364) stated the reasons for non-participation. Overall, the response rate to
      the questionnaire varied with specialty and location of the practice:
      radiotherapists answered significantly more frequently than other categories of
      physician (e.g. general practitioners) and physicians in rural areas
      significantly more frequently than their colleagues in urban areas. The reasons
      most frequently given for non-participation were "Not concerned with the subject"
      and "No time". CONCLUSIONS: The varying rates of response indicate that the
      survey was not sufficiently relevant to all groups of physicians, or that the
      awareness of the topic may be partly underdeveloped.

PMID- 21943380
TI  - The tumour suppressor SOX11 is associated with improved survival among high grade
      epithelial ovarian cancers and is regulated by reversible promoter methylation.
AB  - BACKGROUND: The neural transcription factor SOX11 has been described as a
      prognostic marker in epithelial ovarian cancers (EOC), however its role in
      individual histological subtypes and tumour grade requires further clarification.
      Furthermore, methylation-dependent silencing of SOX11 has been reported for B
      cell lymphomas and indicates that epigenetic drugs may be used to re-express this
      tumour suppressor, but information on SOX11 promoter methylation in EOC is still
      lacking. METHODS: SOX11 expression and clinicopathological data was compared
      using chi2 test in a cohort of 154 cases of primary invasive EOC. Kaplan-Meier
      analysis and the log rank test were applied to evaluate ovarian cancer-specific
      survival (OCSS) and overall survival (OS) in strata, according to SOX11
      expression. Also, the methylation status of the SOX11 promoter was determined by
      sodium bisulfite sequencing and methylation specific PCR (MSP). Furthermore, the
      effect of ectopic overexpression of SOX11 on proliferation was studied through
      [3H]-thymidine incorporation. RESULTS: SOX11 expression was associated with an
      improved survival of patients with high grade EOC, although not independent of
      stage. Further analyses of EOC cell lines showed that SOX11 mRNA and protein were
      expressed in two of five cell lines, correlating with promoter methylation
      status. Demethylation was successfully performed using 5'-Aza-2'deoxycytidine (5
      Aza-dC) resulting in SOX11 mRNA and protein expression in a previously negative
      EOC cell line. Furthermore, overexpression of SOX11 in EOC cell lines confirmed
      the growth regulatory role of SOX11. CONCLUSIONS: SOX11 is a functionally
      associated protein in EOC with prognostic value for high-grade tumours. Re
      expression of SOX11 in EOC indicates a potential use of epigenetic drugs to
      affect cellular growth in SOX11-negative tumours.

PMID- 21943381
TI  - Quality of life among patients undergoing bariatric surgery: associations with
      mental health- A 1 year follow-up study of bariatric surgery patients.
AB  - BACKGROUND: Preoperative mental health seems to have useful predictive value for
      Health Related Quality of Life (HRQOL) after bariatric surgery. The aim of the
      present study was to assess pre- and postoperative psychiatric disorders and
      their associations with pre- and postoperative HRQOL. METHOD: Data were assessed
      before (n = 127) and one year after surgery (n = 87). Psychiatric disorders were
      assessed by Mini International Neuropsychiatric Interview (M.I.N.I.) and
      Structured Clinical Interview (SCID-II). HRQOL was assessed by the Short Form 36
      (SF-36) questionnaire. RESULTS: Significant improvements were found in HRQOL from
      preoperative assessment to follow-up one year after surgery. For the total study
      population, the degree of improvement was statistically significant (p values <
      .001) for seven of the eight SF-36 subscales from preoperative assessment to
      follow-up one year after surgery. Patients without psychiatric disorders had no
      impairments in postoperative HRQOL, and patients with psychiatric disorders that
      resolved after surgery had small impairments on two of the eight SF-36 subscales
      compared to the population norm (all effect sizes < .5) at follow-up one year
      after surgery. Patients with psychiatric disorders that persisted after surgery
      had impaired HRQOL at follow-up one year after surgery compared to the population
      norm, with effect sizes for the differences from moderate to large (all effect
      sizes >= .6). CONCLUSION: This study reports the novel finding that patients
      without postoperative psychiatric disorders achieved a HRQOL comparable to the
      general population one year after bariatric surgery; while patients with
      postoperative psychiatric disorders did not reach the HRQOL level of the general
      population. Our results support monitoring patients with psychiatric disorders
      persisting after surgery for suboptimal improvements in quality of life after
      bariatric surgery. TRIAL REGISTRATION: The trial is registered at
      http://www.clinicaltrials.gov prior to patient inclusion (ProtocolID16280).

PMID- 21943382
TI  - Will emergency and surgical patients participate in and complete alcohol
      interventions? A systematic review.
AB  - BACKGROUND: In the everyday surgical life, staff may experience that patients
      with Alcohol Use Disorders (AUDs) seem reluctant to participate in alcohol
      intervention programs. The objective was therefore to assess acceptance of
      screening and intervention as well as adherence to the intervention program among
      emergency department (ED) and surgical patients with AUDs. METHODS: A systematic
      literature search was followed by extraction of acceptance and adherence rates in
      ED and surgical patients. Numbers needed to screen (NNS) were calculated.
      Subgroup analyses were carried out based on different study characteristics.
      RESULTS: The literature search revealed 33 relevant studies. Of these, 31 were
      randomized trials, 28 were conducted in EDs and 31 evaluated the effect of brief
      alcohol intervention. Follow-up was mainly conducted after six and/or twelve
      months.Four in five ED patients accepted alcohol screening and two in three
      accepted participation in intervention. In surgical patients, two in three
      accepted screening and the intervention acceptance rate was almost 100%. The
      adherence rate was above 60% for up to twelve months in both ED and surgical
      patients. The NNS to identify one eligible AUD patient and to get one eligible
      patient to accept participation in alcohol intervention varied from a few up to
      70 patients.The rates did not differ between randomized and non-randomized
      trials, brief and intensive interventions or validated and self-reported alcohol
      consumption. Adherence rates were not affected by patients' group allocation and
      type of follow-up. CONCLUSIONS: Most emergency and surgical patients with AUD
      accept participation in alcohol screening and interventions and complete the
      intervention program.

PMID- 21943383
TI  - Determinants of polyp size in patients undergoing screening colonoscopy.
AB  - BACKGROUND: Pre-existing polyps, especially large polyps, are known to be the
      major source for colorectal cancer, but there is limited available information
      about factors that are associated with polyp size and polyp growth. We aim to
      determine factors associated with polyp size in different age groups. METHODS:
      Colonoscopy data were prospectively collected from 67 adult gastrointestinal
      practice sites in the United States between 2002 and 2007 using a computer
      generated endoscopic report form. Data were transmitted to and stored in a
      central data repository, where all asymptomatic white (n = 78352) and black (n =
      4289) patients who had a polyp finding on screening colonoscopy were identified.
      Univariate and multivariate analysis of age, gender, performance site, race,
      polyp location, number of polyps, and family history as risk factors associated
      with the size of the largest polyp detected at colonoscopy. RESULTS: In both
      genders, size of the largest polyp increased progressively with age in all age
      groups (P < .0001). In subjects >= 80 years the relative risk was 1.55 (95% CI,
      1.35-1.79) compared to subjects in the youngest age group. With the exception of
      family history, all study variables were significantly associated with polyp size
      (P < .0001), with multiple polyps (>= 2 versus 1) having the strongest risk: 3.41
      (95% CI, 3.29-3.54). CONCLUSIONS: In both genders there is a significant increase
      in polyp size detected during screening colonoscopy with increasing age.
      Important additional risk factors associated with increasing polyp size are
      gender, race, polyp location, and number of polyps, with polyp multiplicity being
      the strongest risk factor. Previous family history of bowel cancer was not a risk
      factor.

PMID- 21943384
TI  - The SCIDOTS Project: evidence of benefits of an integrated tobacco cessation
      intervention in tuberculosis care on treatment outcomes.
AB  - BACKGROUND: There is substantial evidence to support the association between
      tuberculosis (TB) and tobacco smoking and that the smoking-related immunological
      abnormalities in TB are reversible within six weeks of cessation. Therefore,
      connecting TB and tobacco cessation interventions may produce significant
      benefits and positively impact TB treatment outcomes. However, no study has
      extensively documented the evidence of benefits of such integration. SCIDOTS
      Project is a study from the context of a developing nation aimed to determine
      this. METHODS: An integrated TB-tobacco intervention was provided by trained TB
      directly observed therapy short-course (DOTS) providers at five chest clinics in
      Malaysia. The study was a prospective non-randomized controlled intervention
      using quasi-experimental design. Using Transtheoretical Model approach, 120
      eligible participants who were current smokers at the time of TB diagnosis were
      assigned to either of two treatment groups: conventional TB DOTS plus smoking
      cessation intervention (integrated intervention or SCIDOTS group) or conventional
      TB DOTS alone (comparison or DOTS group). At baseline, newly diagnosed TB
      patients considering quitting smoking within the next 30 days were placed in the
      integrated intervention group, while those who were contemplating quitting were
      assigned to the comparison group. Eleven sessions of individualized cognitive
      behavioral therapy with or without nicotine replacement therapy were provided to
      each participant in the integrated intervention group. The impacts of the novel
      approach on biochemically validated smoking cessation and TB treatment outcomes
      were measured periodically as appropriate. RESULTS: A linear effect on both 7-day
      point prevalence abstinence and continuous abstinence was observed over time in
      the intervention group. At the end of 6 months, patients who received the
      integrated intervention had significantly higher rate of success in quitting
      smoking when compared with those who received the conventional TB treatment alone
      (77.5% vs. 8.7%; p < 0.001). Furthermore, at the end of TB treatment (6 months or
      later), there were significantly higher rates of treatment default (15.2% vs.
      2.5%; p = 0.019) and treatment failure (6.5% vs. 0%; p = 0.019) in the DOTS group
      than in the SCIDOTS group. CONCLUSION: This study provides evidence that
      connecting TB-tobacco treatment strategy is significant among TB patients who are
      smokers. The findings suggest that the integrated approach may be beneficial and
      confer advantages on short-term outcomes and possibly on future lung health of TB
      patients who quit smoking. This study may have important implications on health
      policy and clinical practice related to TB management among tobacco users.

PMID- 21943385
TI  - Analytical and numerical solutions of the potential and electric field generated
      by different electrode arrays in a tumor tissue under electrotherapy.
AB  - BACKGROUND: Electrotherapy is a relatively well established and efficient method
      of tumor treatment. In this paper we focus on analytical and numerical
      calculations of the potential and electric field distributions inside a tumor
      tissue in a two-dimensional model (2D-model) generated by means of electrode
      arrays with shapes of different conic sections (ellipse, parabola and hyperbola).
      METHODS: Analytical calculations of the potential and electric field
      distributions based on 2D-models for different electrode arrays are performed by
      solving the Laplace equation, meanwhile the numerical solution is solved by means
      of finite element method in two dimensions. RESULTS: Both analytical and
      numerical solutions reveal significant differences between the electric field
      distributions generated by electrode arrays with shapes of circle and different
      conic sections (elliptic, parabolic and hyperbolic). Electrode arrays with
      circular, elliptical and hyperbolic shapes have the advantage of concentrating
      the electric field lines in the tumor. CONCLUSION: The mathematical approach
      presented in this study provides a useful tool for the design of electrode arrays
      with different shapes of conic sections by means of the use of the unifying
      principle. At the same time, we verify the good correspondence between the
      analytical and numerical solutions for the potential and electric field
      distributions generated by the electrode array with different conic sections.

PMID- 21943386
TI  - Effects of copper nanoparticle exposure on host defense in a murine pulmonary
      infection model.
AB  - BACKGROUND: Human exposure to nanoparticles (NPs) and environmental bacteria can
      occur simultaneously. NPs induce inflammatory responses and oxidative stress but
      may also have immune-suppressive effects, impairing macrophage function and
      altering epithelial barrier functions. The purpose of this study was to assess
      the potential pulmonary effects of inhalation and instillation exposure to copper
      (Cu) NPs using a model of lung inflammation and host defense. METHODS: We used
      Klebsiella pneumoniae (K.p.) in a murine lung infection model to determine if
      pulmonary bacterial clearance is enhanced or impaired by Cu NP exposure. Two
      different exposure modes were tested: sub-acute inhalation (4 hr/day, 5 d/week
      for 2 weeks, 3.5 mg/m(3)) and intratracheal instillation (24 hr post-exposure, 3,
      35, and 100 MUg/mouse). Pulmonary responses were evaluated by lung histopathology
      plus measurement of differential cell counts, total protein, lactate
      dehydrogenase (LDH) activity, and inflammatory cytokines in bronchoalveolar
      lavage (BAL) fluid. RESULTS: Cu NP exposure induced inflammatory responses with
      increased recruitment of total cells and neutrophils to the lungs as well as
      increased total protein and LDH activity in BAL fluid. Both inhalation and
      instillation exposure to Cu NPs significantly decreased the pulmonary clearance
      of K.p.-exposed mice measured 24 hr after bacterial infection following Cu NP
      exposure versus sham-exposed mice also challenged with K.p (1.4 * 10(5)
      bacteria/mouse). CONCLUSIONS: Cu NP exposure impaired host defense against
      bacterial lung infections and induced a dose-dependent decrease in bacterial
      clearance in which even our lowest dose demonstrated significantly lower
      clearance than observed in sham-exposed mice. Thus, exposure to Cu NPs may
      increase the risk of pulmonary infection.

PMID- 21943387
TI  - Metabolic network modeling of redox balancing and biohydrogen production in
      purple nonsulfur bacteria.
AB  - BACKGROUND: Purple nonsulfur bacteria (PNSB) are facultative photosynthetic
      bacteria and exhibit an extremely versatile metabolism. A central focus of
      research on PNSB dealt with the elucidation of mechanisms by which they manage to
      balance cellular redox under diverse conditions, in particular under
      photoheterotrophic growth. RESULTS: Given the complexity of the central
      metabolism of PNSB, metabolic modeling becomes crucial for an integrated analysis
      of the accumulated biological knowledge. We reconstructed a stoichiometric model
      capturing the central metabolism of three important representatives of PNSB
      (Rhodospirillum rubrum, Rhodobacter sphaeroides and Rhodopseudomonas palustris).
      Using flux variability analysis, the model reveals key metabolic constraints
      related to redox homeostasis in these bacteria. With the help of the model we can
      (i) give quantitative explanations for non-intuitive, partially species-specific
      phenomena of photoheterotrophic growth of PNSB, (ii) reproduce various
      quantitative experimental data, and (iii) formulate several new hypotheses. For
      example, model analysis of photoheterotrophic growth reveals that--despite a
      large number of utilizable catabolic pathways--substrate-specific biomass and CO2
      yields are fixed constraints, irrespective of the assumption of optimal growth.
      Furthermore, our model explains quantitatively why a CO2 fixing pathway such as
      the Calvin cycle is required by PNSB for many substrates (even if CO2 is
      released). We also analyze the role of other pathways potentially involved in
      redox metabolism and how they affect quantitatively the required capacity of the
      Calvin cycle. Our model also enables us to discriminate between different acetate
      assimilation pathways that were proposed recently for R. sphaeroides and R.
      rubrum, both lacking the isocitrate lyase. Finally, we demonstrate the value of
      the metabolic model also for potential biotechnological applications: we examine
      the theoretical capabilities of PNSB for photoheterotrophic hydrogen production
      and identify suitable genetic interventions to increase the hydrogen yield.
      CONCLUSIONS: Taken together, the metabolic model (i) explains various redox
      related phenomena of the versatile metabolism of PNSB, (ii) delivers new
      hypotheses on the operation and relevance of several metabolic pathways, and
      (iii) holds significant potential as a tool for rational metabolic engineering of
      PNSB in biotechnological applications.

PMID- 21943388
TI  - Prevalence and risk factors of diabetes and impaired fasting glucose in Nauru.
AB  - BACKGROUND: No comprehensive assessment of diabetes prevalence in Nauru has been
      conducted since an extreme prevalence was documented more than two decades ago.
      This study aims to determine the prevalence and risk factors of diabetes and
      impaired fasting glucose. METHODS: A nationwide survey in 2004 of people aged 15-
      64 years (n = 1592). Fasting plasma glucose levels were used to defined diabetes
      (>= 7.0 mmol/l or 126 mg/dl) and prediabetes (6.1-6.9 mmol/l or 110-125 mg/dl).
      RESULTS: The sex-standardized prevalence of diabetes was 13.0% (95% CI: 10.6,
      15.4) in men, 14.4% (11.9, 16.9) in women, and 13.7% (12.0, 15.4) combined. The
      sex-standardized prevalence of prediabetes was 6.4% (4.6, 8.2) for men, 5.5%
      (3.9, 7.2) for women, and 6.0% (4.8, 7.3) combined. The prevalence of diabetes
      for individuals 15-24, 25-34, 35-44, 45-54 and 55-64 years was 4.5%, 7.6%, 24.1%,
      32.9%, and 42.7%, respectively. The prevalence of prediabetes for the same age
      categories was 4.2%, 8.8%, 5.9%, 6.6%, 7.1%, respectively. Multivariable,
      multinomial logit modeling found risk factors for prediabetes were high
      cholesterol levels (OR: 2.02, 95% CI: 1.66, 2.47) and elevated waist
      circumference (OR: 1.04, 95% CI: 1.00, 1.08), and for diabetes were age in years
      (OR: 1.06; 95% CI: 1.04, 1.07), cholesterol levels (OR: 1.84, 95% CI: 1.58, 2.14)
      and waist circumference (OR: 1.04, 95% CI: 1.02, 1.07). CONCLUSIONS: Diabetes
      remains a major public health problem in Nauru, affecting one out of every ten
      people. While the prevalence of diabetes has declined, its burden has persisted
      among the old but also extended towards the younger age groups.

PMID- 21943389
TI  - Three-dimensional reconstructions of intrahepatic bile duct tubulogenesis in
      human liver.
AB  - BACKGROUND: During liver development, intrahepatic bile ducts are thought to
      arise by a unique asymmetric mode of cholangiocyte tubulogenesis characterized by
      a series of remodeling stages. Moreover, in liver diseases, cells lining the
      Canals of Hering can proliferate and generate new hepatic tissue. The aim of this
      study was to develop protocols for three-dimensional visualization of protein
      expression, hepatic portal structures and human hepatic cholangiocyte
      tubulogenesis. RESULTS: Protocols were developed to digitally visualize portal
      vessel branching and protein expression of hepatic cell lineage and extracellular
      matrix deposition markers in three dimensions. Samples from human prenatal livers
      ranging from 7 weeks + 2 days to 151/2 weeks post conception as well as adult
      normal and acetaminophen intoxicated liver were used. The markers included
      cytokeratins (CK) 7 and 19, the epithelial cell adhesion molecule (EpCAM),
      hepatocyte paraffin 1 (HepPar1), sex determining region Y (SRY)-box 9 (SOX9),
      laminin, nestin, and aquaporin 1 (AQP1).Digital three-dimensional reconstructions
      using CK19 as a single marker protein disclosed a fine network of CK19 positive
      cells in the biliary tree in normal liver and in the extensive ductular reactions
      originating from intrahepatic bile ducts and branching into the parenchyma of the
      acetaminophen intoxicated liver. In the developing human liver, three-dimensional
      reconstructions using multiple marker proteins confirmed that the human
      intrahepatic biliary tree forms through several developmental stages involving an
      initial transition of primitive hepatocytes into cholangiocytes shaping the
      ductal plate followed by a process of maturation and remodeling where the
      intrahepatic biliary tree develops through an asymmetrical form of cholangiocyte
      tubulogenesis. CONCLUSIONS: The developed protocols provide a novel and
      sophisticated three-dimensional visualization of vessels and protein expression
      in human liver during development and disease.

PMID- 21943390
TI  - Reversal of UVA skin photosensitivity and DNA damage in kidney transplant
      recipients by replacing azathioprine.
AB  - Azathioprine is associated with enhanced skin photosensitivity to ultraviolet A
      (UVA) and leads to incorporation of 6-thioguanine (6-TG) into DNA of dividing
      cells. Unlike canonical DNA, 6-TG DNA is damaged by UVA, which comprises more
      than 90% of the ultraviolet reaching earth. Skin photosensitivity to UVA and UVB
      was measured in 48 kidney transplant patients immunosuppressed either by
      azathioprine (n = 32) or mycophenolate (n = 16). In 23 patients, azathioprine was
      subsequently replaced by mycophenolate and skin photosensitivity, DNA 6-TG
      content in peripheral blood mononuclear cells, and susceptibility to UVA-induced
      DNA damage were monitored for up to 2 years. The mean minimal erythema dose to
      UVA on azathioprine was twofold lower than on mycophenolate. Three months after
      replacing azathioprine by mycophenolate mofetil, the minimal erythema dose to UVA
      had increased from 15 to 25 J/cm(2)  (p < 0.001) accompanied by reduced DNA 6-TG
      content. P53 protein expression in irradiated skin indicated reduced
      susceptibility to UVA-induced DNA damage. 6-TG DNA in peripheral blood
      mononuclear cells remained measurable for over 2 years. Replacing azathioprine
      selectively reduced the skin photosensitivity to UVA, attenuated UVA-induced skin
      DNA damage, and is likely based on incorporated 6-TG in DNA.

PMID- 21943391
TI  - ColVI myopathies: where do we stand, where do we go?
AB  - Collagen VI myopathies, caused by mutations in the genes encoding collagen type
      VI (ColVI), represent a clinical continuum with Ullrich congenital muscular
      dystrophy (UCMD) and Bethlem myopathy (BM) at each end of the spectrum, and less
      well-defined intermediate phenotypes in between. ColVI myopathies also share
      common features with other disorders associated with prominent muscle
      contractures, making differential diagnosis difficult. This group of disorders,
      under-recognized for a long time, has aroused much interest over the past decade,
      with important advances made in understanding its molecular pathogenesis. Indeed,
      numerous mutations have now been reported in the COL6A1, COL6A2 and COL6A3 genes,
      a large proportion of which are de novo and exert dominant-negative effects.
      Genotype-phenotype correlations have also started to emerge, which reflect the
      various pathogenic mechanisms at play in these disorders: dominant de novo exon
      splicing that enables the synthesis and secretion of mutant tetramers and
      homozygous nonsense mutations that lead to premature termination of translation
      and complete loss of function are associated with early-onset, severe phenotypes.
      In this review, we present the current state of diagnosis and research in the
      field of ColVI myopathies. The past decade has provided significant advances,
      with the identification of altered cellular functions in animal models of ColVI
      myopathies and in patient samples. In particular, mitochondrial dysfunction and a
      defect in the autophagic clearance system of skeletal muscle have recently been
      reported, thereby opening potential therapeutic avenues.

PMID- 21943392
TI  - Risk communication and informed consent in the medical tourism industry: a
      thematic content analysis of Canadian broker websites.
AB  - BACKGROUND: Medical tourism, thought of as patients seeking non-emergency medical
      care outside of their home countries, is a growing industry worldwide. Canadians
      are amongst those engaging in medical tourism, and many are helped in the process
      of accessing care abroad by medical tourism brokers - agents who specialize in
      making international medical care arrangements for patients. As a key source of
      information for these patients, brokers are likely to play an important role in
      communicating the risks and benefits of undergoing surgery or other procedures
      abroad to their clientele. This raises important ethical concerns regarding
      processes such as informed consent and the liability of brokers in the event that
      complications arise from procedures. The purpose of this article is to examine
      the language, information, and online marketing of Canadian medical tourism
      brokers' websites in light of such ethical concerns. METHODS: An exhaustive
      online search using multiple search engines and keywords was performed to compile
      a comprehensive directory of English-language Canadian medical tourism brokerage
      websites. These websites were examined using thematic content analysis, which
      included identifying informational themes, generating frequency counts of these
      themes, and comparing trends in these counts to the established literature.
      RESULTS: Seventeen websites were identified for inclusion in this study. It was
      found that Canadian medical tourism broker websites varied widely in scope,
      content, professionalism and depth of information. Three themes emerged from the
      thematic content analysis: training and accreditation, risk communication, and
      business dimensions. Third party accreditation bodies of debatable regulatory
      value were regularly mentioned on the reviewed websites, and discussion of
      surgical risk was absent on 47% of the websites reviewed, with limited discussion
      of risk on the remaining ones. Terminology describing brokers' roles was somewhat
      inconsistent across the websites. Finally, brokers' roles in follow up care,
      their prices, and the speed of surgery were the most commonly included business
      dimensions on the reviewed websites. CONCLUSION: Canadian medical tourism brokers
      currently lack a common standard of care and accreditation, and are widely
      lacking in providing adequate risk communication for potential medical tourists.
      This has implications for the informed consent and consequent safety of Canadian
      medical tourists.

PMID- 21943393
TI  - Analyses of the oligopeptide transporter gene family in poplar and grape.
AB  - BACKGROUND: Oligopeptide transporters (OPTs) are a group of membrane-localized
      proteins that have a broad range of substrate transport capabilities and that are
      thought to contribute to many biological processes. The OPT proteins belong to a
      small gene family in plants, which includes about 25 members in Arabidopsis and
      rice. However, no comprehensive study incorporating phylogeny, chromosomal
      location, gene structure, expression profiling, functional divergence and
      selective pressure analysis has been reported thus far for Populus and Vitis.
      RESULTS: In the present study, a comprehensive analysis of the OPT gene family in
      Populus (P. trichocarpa) and Vitis (V. vinifera) was performed. A total of 20 and
      18 full-length OPT genes have been identified in Populus and Vitis, respectively.
      Phylogenetic analyses indicate that these OPT genes consist of two classes that
      can be further subdivided into 11 groups. Gene structures are considerably
      conserved among the groups. The distribution of OPT genes was found to be non
      random across chromosomes. A high proportion of the genes are preferentially
      clustered, indicating that tandem duplications may have contributed significantly
      to the expansion of the OPT gene family. Expression patterns based on our
      analyses of microarray data suggest that many OPT genes may be important in
      stress response and functional development of plants. Further analyses of
      functional divergence and adaptive evolution show that, while purifying selection
      may have been the main force driving the evolution of the OPTs, some of critical
      sites responsible for the functional divergence may have been under positive
      selection. CONCLUSIONS: Overall, the data obtained from our investigation
      contribute to a better understanding of the complexity of the Populus and Vitis
      OPT gene family and of the function and evolution of the OPT gene family in
      higher plants.

PMID- 21943394
TI  - Clinical pharmacogenomic testing of KRAS, BRAF and EGFR mutations by high
      resolution melting analysis and ultra-deep pyrosequencing.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) and its downstream factors
      KRAS and BRAF are mutated in several types of cancer, affecting the clinical
      response to EGFR inhibitors. Mutations in the EGFR kinase domain predict
      sensitivity to the tyrosine kinase inhibitors gefitinib and erlotinib in lung
      adenocarcinoma, while activating point mutations in KRAS and BRAF confer
      resistance to the anti-EGFR monoclonal antibody cetuximab in colorectal cancer.
      The development of new generation methods for systematic mutation screening of
      these genes will allow more appropriate therapeutic choices. METHODS: We describe
      a high resolution melting (HRM) assay for mutation detection in EGFR exons 19-21,
      KRAS codon 12/13 and BRAF V600 using formalin-fixed paraffin-embedded samples.
      Somatic variation of KRAS exon 2 was also analysed by massively parallel
      pyrosequencing of amplicons with the GS Junior 454 platform. RESULTS: We tested
      120 routine diagnostic specimens from patients with colorectal or lung cancer.
      Mutations in KRAS, BRAF and EGFR were observed in 41.9%, 13.0% and 11.1% of the
      overall samples, respectively, being mutually exclusive. For KRAS, six types of
      substitutions were detected (17 G12D, 9 G13D, 7 G12C, 2 G12A, 2 G12V, 2 G12S),
      while V600E accounted for all the BRAF activating mutations. Regarding EGFR, two
      cases showed exon 19 deletions (delE746-A750 and delE746-T751insA) and another
      two substitutions in exon 21 (one showed L858R with the resistance mutation T590M
      in exon 20, and the other had P848L mutation). Consistent with earlier reports,
      our results show that KRAS and BRAF mutation frequencies in colorectal cancer
      were 44.3% and 13.0%, respectively, while EGFR mutations were detected in 11.1%
      of the lung cancer specimens. Ultra-deep amplicon pyrosequencing successfully
      validated the HRM results and allowed detection and quantitation of KRAS somatic
      mutations. CONCLUSIONS: HRM is a rapid and sensitive method for moderate
      throughput cost-effective screening of oncogene mutations in clinical samples.
      Rather than Sanger sequence validation, next-generation sequencing technology
      results in more accurate quantitative results in somatic variation and can be
      achieved at a higher throughput scale.

PMID- 21943395
TI  - Directed PCR-free engineering of highly repetitive DNA sequences.
AB  - BACKGROUND: Highly repetitive nucleotide sequences are commonly found in nature
      e.g. in telomeres, microsatellite DNA, polyadenine (poly(A)) tails of eukaryotic
      messenger RNA as well as in several inherited human disorders linked to
      trinucleotide repeat expansions in the genome. Therefore, studying repetitive
      sequences is of biological, biotechnological and medical relevance. However,
      cloning of such repetitive DNA sequences is challenging because specific PCR
      based amplification is hampered by the lack of unique primer binding sites
      resulting in unspecific products. RESULTS: For the PCR-free generation of
      repetitive DNA sequences we used antiparallel oligonucleotides flanked by
      restriction sites of Type IIS endonucleases. The arrangement of recognition sites
      allowed for stepwise and seamless elongation of repetitive sequences. This
      facilitated the assembly of repetitive DNA segments and open reading frames
      encoding polypeptides with periodic amino acid sequences of any desired length.
      By this strategy we cloned a series of polyglutamine encoding sequences as well
      as highly repetitive polyadenine tracts. Such repetitive sequences can be used
      for diverse biotechnological applications. As an example, the polyglutamine
      sequences were expressed as His6-SUMO fusion proteins in Escherichia coli cells
      to study their aggregation behavior in vitro. The His6-SUMO moiety enabled
      affinity purification of the polyglutamine proteins, increased their solubility,
      and allowed controlled induction of the aggregation process. We successfully
      purified the fusions proteins and provide an example for their applicability in
      filter retardation assays. CONCLUSION: Our seamless cloning strategy is PCR-free
      and allows the directed and efficient generation of highly repetitive DNA
      sequences of defined lengths by simple standard cloning procedures.

PMID- 21943396
TI  - Barriers and progress in the treatment of low back pain.
AB  - Low back pain is a common and costly condition and for most people is likely to
      be a recurrent problem throughout their lifetime. The management of patients with
      low back pain has been positively influenced by the rise in high quality clinical
      trials and systematic reviews in recent decades, and this body of evidence,
      synthesized in many clinical practice guidelines, has improved our knowledge
      about which treatments for low back pain are useful and which are not. For the
      largest group of patients, those with non-specific low back pain for whom a clear
      diagnosis cannot be given, the reality is that the treatments we have to offer
      tend to produce small effects, often only in the short term and none appear to
      effectively change long-term prognosis. This commentary summarizes the array of
      treatments currently available, notes the results of recent trials and guidelines
      and considers alternative approaches that may prove more valuable in achieving
      better patient outcomes in the future.

PMID- 21943397
TI  - CFTR mediates noradrenaline-induced ATP efflux from DRG neurons.
AB  - In our earlier study, noradrenaline (NA) stimulated ATP release from dorsal root
      ganglion (DRG) neurons as mediated via beta(3) adrenoceptors linked to G(s)
      protein involving protein kinase A (PKA) activation, to cause allodynia. The
      present study was conducted to understand how ATP is released from DRG neurons.
      In an outside-out patch-clamp configuration from acutely dissociated rat DRG
      neurons, single-channel currents, sensitive to the P2X receptor inhibitor PPADS,
      were evoked by approaching the patch-electrode tip close to a neuron, indicating
      that ATP is released from DRG neurons, to activate P2X receptor. NA increased the
      frequency of the single-channel events, but such NA effect was not found for DRG
      neurons transfected with the siRNA to silence the cystic fibrosis transmembrane
      conductance regulator (CFTR) gene. In the immunocytochemical study using acutely
      dissociated rat DRG cells, CFTR was expressed in neurons alone, but not satellite
      cells, fibroblasts, or Schwann cells. It is concluded from these results that
      CFTR mediates NA-induced ATP efflux from DRG neurons as an ATP channel.

PMID- 21943398
TI  - Evaluation of physical activity programmes for the elderly - exploring the
      lessons from other sectors and examining the general characteristics of the
      programmes.
AB  - BACKGROUND: In Portugal, there are several physical activity (PA) programmes for
      elderly people developed by the local government. The importance of these
      programmes has been increasing since the evidence has shown that this type of
      health promotion interventions may reduce the deleterious effects of the ageing
      process. However, no study has already identified the general characteristics of
      these programmes nor if they use any scheme to assess the quality of the service
      provided. A widely-used scheme is the EFQM Excellence Model, which will be in the
      core of our present work. Thus, the main aims of this preliminary study were 1)
      to identify the general characteristics of the PA programmes developed by the
      Portuguese Local Public Administration 2) to determine the extent of
      implementation of quality initiatives in these programmes. METHODS: Data were
      collected by an on-line questionnaire sent to all Continental Municipalities (n =
      278). Categorical data were expressed as absolute counts and percentages.
      Continuous data were expressed as the mean and SD. An open-ended question was
      analysed using qualitative content analysis with QSR NVivo software. Associations
      between categorical variables were tested by the use of contingency tables and
      the calculation of chi-square tests. Significance level was set at p <= 0.05.
      RESULTS: Results showed: i) a total of 125 PA programmes were identified in the
      18 districts of the Portugal mainland; ii) the main goal of the majority (95.2%)
      was the participants' health promotion; iii) different characteristics of the
      programmes were found according to different regions of the country; iv) certain
      characteristics of the programmes were associated to the existence of other
      features; v) only one PA programme developed quality initiatives. CONCLUSIONS: In
      conclusion, although there are many PA programmes for elderly people spread
      throughout the country, aiming at improving the health of participants, the
      overwhelming majority does not adopt quality control initiatives. Considering
      that the quality of a service increases customer satisfaction, the continuous
      quality improvement of the PA programmes for elderly people should therefore be
      implemented since they can be useful and critical for elderly satisfaction and
      adherence.

PMID- 21943399
TI  - Evaluation of early imaging response criteria in glioblastoma multiforme.
AB  - BACKGROUND: Early and accurate prediction of response to cancer treatment through
      imaging criteria is particularly important in rapidly progressive malignancies
      such as Glioblastoma Multiforme (GBM). We sought to assess the predictive value
      of structural imaging response criteria one month after concurrent chemotherapy
      and radiotherapy (RT) in patients with GBM. METHODS: Thirty patients were
      enrolled from 2005 to 2007 (median follow-up 22 months). Tumor volumes were
      delineated at the boundary of abnormal contrast enhancement on T1-weighted images
      prior to and 1 month after RT. Clinical Progression [CP] occurred when clinical
      and/or radiological events led to a change in chemotherapy management. Early
      Radiologic Progression [ERP] was defined as the qualitative interpretation of
      radiological progression one month post-RT. Patients with ERP were determined
      pseudoprogressors if clinically stable for >=6 months. Receiver-operator
      characteristics were calculated for RECIST and MacDonald criteria, along with
      alternative thresholds against 1 year CP-free survival and 2 year overall
      survival (OS). RESULTS: 13 patients (52%) were found to have ERP, of whom 5
      (38.5%) were pseudoprogressors. Patients with ERP had a lower median OS (11.2 mo)
      than those without (not reached) (p < 0.001). True progressors fared worse than
      pseudoprogressors (median survival 7.2 mo vs. 19.0 mo, p < 0.001). Volume
      thresholds performed slightly better compared to area and diameter thresholds in
      ROC analysis. Responses of > 25% in volume or > 15% in area were most predictive
      of OS. CONCLUSIONS: We show that while a subjective interpretation of early
      radiological progression from baseline is generally associated with poor outcome,
      true progressors cannot be distinguished from pseudoprogressors. In contrast, the
      magnitude of early imaging volumetric response may be a predictive and
      quantitative metric of favorable outcome.

PMID- 21943400
TI  - Smoking behaviour predicts tobacco control attitudes in a high smoking prevalence
      hospital: a cross-sectional study in a Portuguese teaching hospital prior to the
      national smoking ban.
AB  - BACKGROUND: Several studies have investigated attitudes to and compliance with
      smoking bans, but few have been conducted in healthcare settings and none in such
      a setting in Portugal. Portugal is of particular interest because the current ban
      is not in line with World Health Organization recommendations for a "100% smoke
      free" policy. In November 2007, a Portuguese teaching-hospital surveyed smoking
      behaviour and tobacco control (TC) attitudes before the national ban came into
      force in January 2008. METHODS: Questionnaire-based cross-sectional study,
      including all eligible staff. SAMPLE: 52.9% of the 1, 112 staff; mean age 38.3 +/
      9.9 years; 65.9% females. Smoking behaviour and TC attitudes and beliefs were
      the main outcomes. Bivariable analyses were conducted using chi-squared and
      MacNemar tests to compare categorical variables and Mann-Whitney tests to compare
      medians. Multilogistic regression (MLR) was performed to identify factors
      associated with smoking status and TC attitudes. RESULTS: Smoking prevalence was
      40.5% (95% CI: 33.6-47.4) in males, 23.5% (95% CI: 19.2-27.8) in females (p <
      0.001); 43.2% in auxiliaries, 26.1% in nurses, 18.9% among physicians, and 34.7%
      among other non-health professionals (p = 0.024). The findings showed a very high
      level of agreement with smoking bans, even among smokers, despite the fact that
      70.3% of the smokers smoked on the premises and 76% of staff reported being
      frequently exposed to second-hand smoke (SHS). In addition 42.8% reported that
      SHS was unpleasant and 28.3% admitted complaining. MLR showed that smoking
      behaviour was the most important predictor of TC attitudes. CONCLUSIONS: Smoking
      prevalence was high, especially among the lower socio-economic groups. The
      findings showed a very high level of support for smoking bans, despite the pro
      smoking environment. Most staff reported passive behaviour, despite high SHS
      exposure. This and the high smoking prevalence may contribute to low compliance
      with the ban and low participation on smoking cessation activities. Smoking
      behaviour had greater influence in TC attitudes than health professionals'
      education. Our study is the first in Portugal to identify potential predictors of
      non-compliance with the partial smoking ban, further emphasising the need for a
      100% smoke-free policy, effective enforcement and public health education to
      ensure compliance and promote social norm change.

PMID- 21943401
TI  - Resilience of refugees displaced in the developing world: a qualitative analysis
      of strengths and struggles of urban refugees in Nepal.
AB  - BACKGROUND: Mental health and psychosocial wellbeing are key concerns in
      displaced populations. Despite urban refugees constituting more than half of the
      world's refugees, minimal attention has been paid to their psychosocial
      wellbeing. The purpose of this study was to assess coping behaviour and aspects
      of resilience amongst refugees in Kathmandu, Nepal. METHODS: This study examined
      the experiences of 16 Pakistani and 8 Somali urban refugees in Kathmandu, Nepal
      through in-depth individual interviews, focus groups, and Photovoice methodology.
      Such qualitative approaches enabled us to broadly discuss themes such as personal
      experiences of being a refugee in Kathmandu, perceived causes of psychosocial
      distress, and strategies and resources for coping. Thematic network analysis was
      used in this study to systematically interpret and code the data. RESULTS: Our
      findings highlight that urban refugees' active coping efforts, notwithstanding
      significant adversity and resulting distress, are most frequently through primary
      relationships. Informed by Axel Honneth's theory on the struggle for recognition,
      findings suggest that coping is a function beyond the individual and involves the
      ability to negotiate recognition. This negotiation involves not only primary
      relationships, but also the legal order and other social networks such as family
      and friends. Honneth's work was used because of its emphasis on the importance of
      legal recognition and larger structural factors in facilitating daily coping.
      CONCLUSIONS: Understanding how urban refugees cope by negotiating access to
      various forms of recognition in the absence of legal-recognition will enable
      organisations working with them to leverage such strengths and develop relevant
      programmes. In particular, building on these existing resources will lead to
      culturally compelling and sustainable care for these populations.

PMID- 21943402
TI  - The phylogenomic analysis of the anaphase promoting complex and its targets
      points to complex and modern-like control of the cell cycle in the last common
      ancestor of eukaryotes.
AB  - BACKGROUND: The Anaphase Promoting Complex or Cyclosome (APC/C) is the largest
      member of the ubiquitin ligase [E3] family. It plays a crucial role in the
      control of the cell cycle and cell proliferation by mediating the proteolysis of
      key components by the proteasome. APC/C is made of a dozen subunits that assemble
      into a large complex of ~1.5 MDa, which interacts with various cofactors and
      targets. RESULTS: Using comparative genomic and phylogenetic approaches, we
      showed that 24 out of 37 known APC/C subunits, adaptors/co-activators and main
      targets, were already present in the Last Eukaryotic Common Ancestor (LECA) and
      were well conserved to a few exceptions in all present-day eukaryotic lineages.
      The phylogenetic analysis of the 24 components inferred to be present in LECA
      showed that they contain a reliable phylogenetic signal to reconstruct the
      phylogeny of the domain Eucarya. CONCLUSIONS: Taken together our analyses
      indicated that LECA had a complex and highly controlled modern-like cell cycle.
      Moreover, we showed that, despite what is generally assumed, proteins involved in
      housekeeping cellular functions may be a good complement to informational genes
      to study the phylogeny of eukaryotes.

PMID- 21943403
TI  - A tool to measure the attributes of receiving IV therapy in a home versus
      hospital setting: the Multiple Sclerosis Relapse Management Scale (MSRMS).
AB  - BACKGROUND: Intravenous steroids are routinely used to treat disabling relapses
      in multiple sclerosis (MS). Theoretically, the infusion could take place at home,
      rather than in hospital. Findings from other patient populations suggest that
      patients may find the experiences of home relapse management more desirable.
      However, formal comparison of these two settings, from the patients' point of
      view, was prevented by the lack of a clinical scale. We report the development of
      a rating scale to measure patient's experiences of relapse management that
      allowed this question to be answered confidently. METHODS: Scale development had
      three stages. First, in-depth interviews of 21 MS patients generated a conceptual
      model and pool of potential scale items. Second, these items were administered to
      160 people with relapsing-remitting MS. Standard psychometric techniques were
      used to develop a scale. Third, the psychometric properties of the scale were
      evaluated in a randomised controlled trial of 138 patients whose relapses were
      managed either at home or hospital. RESULTS: A preliminary conceptual model with
      eight dimensions, and a pool of 154 items was generated. From this we developed
      the MS Relapse Management Scale (MSRMS), a 42-item with four subscales: access to
      care (6 items), coordination of care (11 items), information (7 items),
      interpersonal care (18 items). The MSRMS subscales satisfied most psychometric
      criteria but had notable floor effects. CONCLUSIONS: The MSRMS is a reliable and
      valid measure of patients' experiences of MS relapse management. The high floor
      effects suggest most respondents had positive care experiences. Results
      demonstrate that patients' experiences of relapse management can be measured, and
      that the MSRMS is a powerful tool for determining which services to develop,
      support and ultimately commission.

PMID- 21943404
TI  - Transient knockdown and overexpression reveal a developmental role for the
      zebrafish enosf1b gene.
AB  - BACKGROUND: Despite detailed in vivo knowledge of glycolytic enolases and many
      bacterial non-enolase members of the superfamily, little is known about the in
      vivo function of vertebrate non-enolase enolase superfamily members (ENOSF1s).
      Results of previous studies suggest involvement of the beta splice form of ENOSF1
      in breast and colon cancers. This study used the zebrafish (Danio rerio) as a
      vertebrate model of ENOSF1beta function. RESULTS: Whole mount in situ
      hybridization (WISH) showed that zebrafish ENOSF1beta (enosf1b) is zygotic and
      expressed ubiquitously through the first 24 hours post fertilization (hpf). After
      24 hpf, enosf1b expression is restricted to the notochord. Embryos injected with
      enosf1b-EGFP mRNA grew slower than EGFP mRNA-injected embryos but caught up to
      the EGFP-injected embryos by 48 hpf. Embryos injected with ATG or exon 10 enosf1b
      mRNA-targeting morpholinos had kinked notochords, shortened anterior-posterior
      axes, and circulatory edema. WISH for ntl or pax2a expression showed that embryos
      injected with either morpholino have deformed notochord and pronephros. TUNEL
      staining revealed increased apoptosis in the peri-notochord region. CONCLUSIONS:
      This study is the first report of ENOSF1 function in a vertebrate and shows that
      ENOSF1 is required for embryonic development. Increased apoptosis following
      enosf1b knockdown suggests a potential survival advantage for increased
      ENOSF1beta expression in human cancers.

PMID- 21943405
TI  - Revisiting the Acanthamoeba species that form star-shaped cysts (genotypes T7,
      T8, T9, and T17): characterization of seven new Brazilian environmental isolates
      and phylogenetic inferences.
AB  - Free-living amoebae of the genus Acanthamoeba are the agents of both
      opportunistic and non-opportunistic infections and are frequently isolated from
      the environment. Of the 17 genotypes (T1-T17) identified thus far, 4 (T7, T8, T9,
      and T17) accommodate the rarely investigated species of morphological group I,
      those that form large, star-shaped cysts. We report the isolation and
      characterization of 7 new Brazilian environmental Acanthamoeba isolates, all
      assigned to group I. Phylogenetic analyses based on partial (~1200 bp) SSU rRNA
      gene sequences placed the new isolates in the robustly supported clade composed
      of the species of morphological group I. One of the Brazilian isolates is closely
      related to A. comandoni (genotype T9), while the other 6, together with 2
      isolates recently assigned to genotype T17, form a homogeneous, well-supported
      group (2.0% sequence divergence) that likely represents a new Acanthamoeba
      species. Thermotolerance, osmotolerance, and cytophatic effects, features often
      associated with pathogenic potential, were also examined. The results indicated
      that all 7 Brazilian isolates grow at temperatures up to 40 degrees C, and resist
      under hyperosmotic conditions. Additionally, media conditioned by each of the new
      Acanthamoeba isolates induced the disruption of SIRC and HeLa cell monolayers.

PMID- 21943407
TI  - Nuclease-resistant immunostimulatory phosphodiester CpG oligodeoxynucleotides as
      human Toll-like receptor 9 agonists.
AB  - BACKGROUND: Unmethylated cytosine-guanine (CpG) motif-containing
      oligodeoxynucleotides (ODNs) have been well characterized as agonists of Toll
      like receptor 9 (TLR9). ODNs with a phosphorothioate (PTO) backbone have been
      studied as TLR9 agonists since natural ODNs with a phosphodiester (PD) backbone
      are easily degraded by a serum nuclease, which makes them problematic for
      therapeutic applications. However, ODNs with a PTO backbone have been shown to
      have undesirable side effects. Thus, our goal was to develop nuclease-resistant,
      PD ODNs that are effective as human TLR9 (hTLR9) agonists. RESULTS: The sequence
      of ODN2006, a CpG ODN that acts as an hTLR9 agonist, was used as the basic CpG
      ODN material. The 3'-end modification of ODN2006 with a PD backbone (PD-ODN2006)
      improved its potential as an hTLR9 agonist because of increased resistance to
      nucleolytic degradation. Moreover, 3'-end modification with oligonucleotides
      showed higher induction than modification with biotin, FITC, and amino groups.
      Further, enhancement of hTLR9 activity was found to be dependent on the number of
      CpG core motifs (GTCGTT) in the PD ODN containing the 3'-end oligonucleotides. In
      particular, ODN sequences consisting of two to three linked ODN2006 sequences
      with a PD backbone (e.g., PD-ODN2006-2006 and PD-ODN2006-2006-2006) acted as
      effective agonists of hTLR9 even at lower concentrations. CONCLUSIONS: This study
      showed that PD-ODN2006-2006 and PD-ODN-2006-2006-2006 can be used as potentially
      safe agonists for hTLR9 activation instead of CpG ODNs with a PTO backbone. We
      propose these CpG ODNs consisting of only a PD backbone as a novel class of CpG
      ODN.

PMID- 21943406
TI  - Ethical issues at the interface of clinical care and research practice in
      pediatric oncology: a narrative review of parents' and physicians' experiences.
AB  - BACKGROUND: Pediatric oncology has a strong research culture. Most pediatric
      oncologists are investigators, involved in clinical care as well as research. As
      a result, a remarkable proportion of children with cancer enrolls in a trial
      during treatment. This paper discusses the ethical consequences of the
      unprecedented integration of research and care in pediatric oncology from the
      perspective of parents and physicians. METHODOLOGY: An empirical ethical
      approach, combining (1) a narrative review of (primarily) qualitative studies on
      parents' and physicians' experiences of the pediatric oncology research practice,
      and (2) comparison of these experiences with existing theoretical ethical
      concepts about (pediatric) research. The use of empirical evidence enriches these
      concepts by taking into account the peculiarities that ethical challenges pose in
      practice. RESULTS: Analysis of the 22 studies reviewed revealed that the
      integration of research and care has consequences for the informed consent
      process, the promotion of the child's best interests, and the role of the
      physician (doctor vs. scientist). True consent to research is difficult to
      achieve due to the complexity of research protocols, emotional stress and
      parents' dependency on their child's physician. Parents' role is to promote their
      child's best interests, also when they are asked to consider enrolling their
      child in a trial. Parents are almost never in equipoise on trial participation,
      which leaves them with the agonizing situation of wanting to do what is best for
      their child, while being fearful of making the wrong decision. Furthermore, a
      therapeutic misconception endangers correct assessment of participation, making
      parents inaccurately attribute therapeutic intent to research procedures.
      Physicians prefer the perspective of a therapist over a researcher. Consequently
      they may truly believe that in the research setting they promote the child's best
      interests, which maintains the existence of a therapeutic misconception between
      them and parents. CONCLUSION: Due to the integration of research and care, their
      different ethical perspectives become intertwined in the daily practice of
      pediatric oncology. Increasing awareness of what this means for the communication
      between parents and physicians is essential. Future research should focus on
      efforts that overcome the problems that the synchronicity of research and care
      evokes.

PMID- 21943408
TI  - Activation of retinal microglia rather than microglial cell density correlates
      with retinal neovascularization in the mouse model of oxygen-induced retinopathy.
AB  - BACKGROUND: Retinal neovascularization has been intensively investigated in the
      mouse model of oxygen-induced retinopathy (OIR). Here, we studied the
      contribution of microglial cells to vascular regression during the hyperoxic
      phase and to retinal neovascularization during the hypoxic phase. METHODS: Mice
      expressing green fluorescent protein (GFP) under the Cx3cr1 promoter labeling
      microglial cells were kept in 75% oxygen from postnatal day 7 (P7) to P12.
      Microglial cell density was quantified at different time points and at different
      retinal positions in retinal flat mounts. Microglial activation was determined by
      the switch from ramified to amoeboid cell morphology which correlated with the
      switch from lectin negative to lectin positive staining of GFP positive cells.
      RESULTS: Microglial cell density was constant in the peripheral region of the
      retina. In the deep vascular layer of the central region, however, it declined 14
      fold from P12 to P14 and recovered afterwards. Activated microglial cells were
      found in the superficial layer of the central avascular zone from P8 to P12 and
      from P16 to P18. In addition, hyalocytes were found in the vitreal layer in the
      central region and their cell density decreased over time. CONCLUSION: Density of
      microglial cells does not correlate with vascular obliteration or
      revascularization. But the time course of the activation of microglia indicates
      that they may be involved in retinal neovascularization during the hypoxic phase.

PMID- 21943409
TI  - Dynamics of calcium sparks and calcium leak in the heart.
AB  - We present what we believe to be a new mathematical model of Ca(2+) leak from the
      sarcoplasmic reticulum (SR) in the heart. To our knowledge, it is the first to
      incorporate a realistic number of Ca(2+)-release units, each containing a cluster
      of stochastically gating Ca(2+) channels (RyRs), whose biophysical properties
      (e.g., Ca(2+) sensitivity and allosteric interactions) are informed by the latest
      molecular investigations. This realistic model allows for the detailed
      characterization of RyR Ca(2+)-release properties, and shows how this balances
      reuptake by the SR Ca(2+) pump. Simulations reveal that SR Ca(2+) leak consists
      of brief but frequent single RyR openings (~3000 cell(-1) s(-1)) that are likely
      to be experimentally undetectable, and are, therefore, "invisible". We also
      observe that these single RyR openings can recruit additional RyRs to open, due
      to elevated local (Ca(2+)), and occasionally lead to the generation of Ca(2+)
      sparks (~130 cell(-1) s(-1)). Furthermore, this physiological formulation of
      "invisible" leak allows for the removal of the ad hoc, non-RyR mediated Ca(2+)
      leak terms present in prior models. Finally, our model shows how Ca(2+) sparks
      can be robustly triggered and terminated under both normal and pathological
      conditions. Together, these discoveries profoundly influence how we interpret and
      understand diverse experimental and clinical results from both normal and
      diseased hearts.

PMID- 21943410
TI  - On the minimization of fluctuations in the response times of autoregulatory gene
      networks.
AB  - The temporal dynamics of the concentrations of several proteins are tightly
      regulated, particularly for critical nodes in biological networks such as
      transcription factors. An important mechanism to control transcription factor
      levels is through autoregulatory feedback loops where the protein can bind its
      own promoter. Here we use theoretical tools and computational simulations to
      further our understanding of transcription-factor autoregulatory loops. We show
      that the stochastic dynamics of feedback and mRNA synthesis can significantly
      influence the speed of response of autoregulatory genetic networks toward
      external stimuli. The fluctuations in the response-times associated with the
      accumulation of the transcription factor in the presence of negative or positive
      autoregulation can be minimized by confining the ratio of mRNA/protein lifetimes
      within 1:10. This predicted range of mRNA/protein lifetime agrees with ranges
      observed empirically in prokaryotes and eukaryotes. The theory can quantitatively
      and systematically account for the influence of regulatory element binding and
      unbinding dynamics on the transcription-factor concentration rise-times. The
      simulation results are robust against changes in several system parameters of the
      gene expression machinery.

PMID- 21943411
TI  - Susceptibility to arrhythmia in the infarcted heart depends on myofibroblast
      density.
AB  - Fibroblasts are electrophysiologically quiescent in the healthy heart. Evidence
      suggests that remodeling following myocardial infarction may include coupling of
      myofibroblasts (Mfbs) among themselves and with myocytes via gap junctions. We
      use a magnetic resonance imaging-based, three-dimensional computational model of
      the chronically infarcted rabbit ventricles to characterize the arrhythmogenic
      substrate resulting from Mfb infiltration as a function of Mfb density. Mfbs
      forming gap junctions were incorporated into both infarct regions, the
      periinfarct zone (PZ) and the scar; six scenarios were modeled: 0%, 10%, and 30%
      Mfbs in the PZ, with either 80% or 0% Mfbs in the scar. Ionic current remodeling
      in PZ was also included. All preparations exhibited elevated resting membrane
      potential within and near the PZ and action potential duration shortening
      throughout the ventricles. The unique combination of PZ ionic current remodeling
      and different degrees of Mfb infiltration in the infarcted ventricles determines
      susceptibility to arrhythmia. At low densities, Mfbs do not alter arrhythmia
      propensity; the latter arises predominantly from ionic current remodeling in PZ.
      At intermediate densities, Mfbs cause additional action potential shortening and
      exacerbate arrhythmia propensity. At high densities, Mfbs protect against
      arrhythmia by causing resting depolarization and blocking propagation, thus
      overcoming the arrhythmogenic effects of PZ ionic current remodeling.

PMID- 21943412
TI  - Divalent counterions tether membrane-bound carbohydrates to promote the cohesion
      of auditory hair bundles.
AB  - The cell membranes in the hair bundle of an auditory hair cell confront a
      difficult task as the bundle oscillates in response to sound: for efficient
      mechanotransduction, all the component stereocilia of the hair bundle must move
      essentially in unison, shearing at their tips yet maintaining contact without
      membrane fusion. One mechanism by which this cohesion might occur is counterion
      mediated attachment between glycan components of apposed stereociliary membranes.
      Using capillary electrophoresis, we showed that the stereociliary glycocalyx acts
      as a negatively charged polymer brush. We found by force-sensing photomicrometry
      that the stereocilia formed elastic connections with one another to various
      degrees depending on the surrounding ionic environment and the presence of N
      linked sugars. Mg(2+) was a more potent mediator of attachment than was Ca(2+).
      The forces between stereocilia produced chaotic stick-slip behavior. These
      results indicate that counterion-mediated interactions in the glycocalyx
      contribute to the stereociliary coherence that is essential for hearing.

PMID- 21943413
TI  - Multiscale computational models for optogenetic control of cardiac function.
AB  - The ability to stimulate mammalian cells with light has significantly changed our
      understanding of electrically excitable tissues in health and disease, paving the
      way toward various novel therapeutic applications. Here, we demonstrate the
      potential of optogenetic control in cardiac cells using a hybrid
      experimental/computational technique. Experimentally, we introduced
      channelrhodopsin-2 into undifferentiated human embryonic stem cells via a
      lentiviral vector, and sorted and expanded the genetically engineered cells. Via
      directed differentiation, we created channelrhodopsin-expressing cardiomyocytes,
      which we subjected to optical stimulation. To quantify the impact of
      photostimulation, we assessed electrical, biochemical, and mechanical signals
      using patch-clamping, multielectrode array recordings, and video microscopy.
      Computationally, we introduced channelrhodopsin-2 into a classic autorhythmic
      cardiac cell model via an additional photocurrent governed by a light-sensitive
      gating variable. Upon optical stimulation, the channel opens and allows sodium
      ions to enter the cell, inducing a fast upstroke of the transmembrane potential.
      We calibrated the channelrhodopsin-expressing cell model using single action
      potential readings for different photostimulation amplitudes, pulse widths, and
      frequencies. To illustrate the potential of the proposed approach, we virtually
      injected channelrhodopsin-expressing cells into different locations of a human
      heart, and explored its activation sequences upon optical stimulation. Our
      experimentally calibrated computational toolbox allows us to virtually probe
      landscapes of process parameters, and identify optimal photostimulation sequences
      toward pacing hearts with light.

PMID- 21943414
TI  - Landscape, flux, correlation, resonance, coherence, stability, and key network
      wirings of stochastic circadian oscillation.
AB  - Circadian rhythms with a period of ~24 h, are natural timing machines. They are
      broadly distributed in living organisms, such as Neurospora, Drosophila, and
      mammals. The underlying natures of the rhythmic behavior have been explored by
      experimental and theoretical approaches. However, the global and physical natures
      of the oscillation under fluctuations are still not very clear. We developed a
      landscape and flux framework to explore the global stability and robustness of a
      circadian oscillation system. The potential landscape of the network is uncovered
      and has a global Mexican-hat shape. The height of the Mexican-hat provides a
      quantitative measure to evaluate the robustness and coherence of the oscillation.
      We found that in nonequilibrium dynamic systems, not only the potential landscape
      but also the probability flux are important to the dynamics of the system under
      intrinsic noise. Landscape attracts the systems down to the oscillation ring
      while flux drives the coherent oscillation on the ring. We also investigated the
      phase coherence and the entropy production rate of the system at different
      fluctuations and found that dissipations are less and the coherence is higher for
      larger number of molecules. We also found that the power spectrum of
      autocorrelation functions show resonance peak at the frequency of coherent
      oscillations. The peak is less prominent for smaller number of molecules and less
      barrier height and therefore can be used as another measure of stability of
      oscillations. As a consequence of nonzero probability flux, we show that the
      three-point correlations from the time traces show irreversibility, providing a
      possible way to explore the flux from the observations. Furthermore, we explored
      the escape time from the oscillation ring to outside at different molecular
      number. We found that when barrier height is higher, escape time is longer and
      phase coherence of oscillation is higher. Finally, we performed the global
      sensitivity analysis of the underlying parameters to find the key network wirings
      responsible for the stability of the oscillation system.

PMID- 21943415
TI  - Time-resolved WAXS reveals accelerated conformational changes in iodoretinal
      substituted proteorhodopsin.
AB  - Time-resolved wide-angle x-ray scattering (TR-WAXS) is an emerging biophysical
      method which probes protein conformational changes with time. Here we present a
      comparative TR-WAXS study of native green-absorbing proteorhodopsin (pR) from
      SAR86 and a halogenated derivative for which the retinal chromophore has been
      replaced with 13-desmethyl-13-iodoretinal (13-I-pR). Transient absorption
      spectroscopy differences show that the 13-I-pR photocycle is both accelerated and
      displays more complex kinetics than native pR. TR-WAXS difference data also
      reveal that protein structural changes rise and decay an order-of-magnitude more
      rapidly for 13-I-pR than native pR. Despite these differences, the amplitude and
      nature of the observed helical motions are not significantly affected by the
      substitution of the retinal's C-20 methyl group with an iodine atom. Molecular
      dynamics simulations indicate that a significant increase in free energy is
      associated with the 13-cis conformation of 13-I-pR, consistent with our
      observation that the transient 13-I-pR conformational state is reached more
      rapidly. We conclude that although the conformational trajectory is accelerated,
      the major transient conformation of pR is unaffected by the substitution of an
      iodinated retinal chromophore.

PMID- 21943416
TI  - KCNE1 and KCNE2 inhibit forward trafficking of homomeric N-type voltage-gated
      potassium channels.
AB  - Potassium currents generated by voltage-gated potassium (Kv) channels comprising
      alpha-subunits from the Kv1, 2, and 3 subfamilies facilitate high-frequency
      firing of mammalian neurons. Within these subfamilies, only three alpha-subunits
      (Kv1.4, Kv3.3, and Kv3.4) generate currents that decay rapidly in the open state
      because an N-terminal ball domain blocks the channel pore after activation-a
      process termed N-type inactivation. Despite its importance to shaping cellular
      excitability, little is known of the processes regulating surface expression of N
      type alpha-subunits, versus their slowly inactivating (delayed rectifier)
      counterparts. Here we found that currents generated by homomeric Kv1.4, Kv3.3,
      and Kv3.4 channels are all strongly suppressed by the single transmembrane domain
      ancillary (beta) subunits KCNE1 and KCNE2. A combination of electrophysiological,
      biochemical, and immunofluorescence analyses revealed this suppression is due to
      KCNE1 and KCNE2 retaining Kv1.4 and Kv3.4 intracellularly, early in the secretory
      pathway. The retention is specific, requires alpha-beta coassembly, and does not
      involve the dynamin-dependent endocytosis pathway. However, the small fraction of
      Kv3.4 that escapes KCNE-dependent retention is regulated by dynamin-dependent
      endocytosis. The findings illustrate two contrasting mechanisms controlling
      surface expression of N-type Kv alpha-subunits and therefore, potentially,
      cellular excitability and refractory periods.

PMID- 21943418
TI  - Oxidized phosphatidylcholines facilitate phospholipid flip-flop in liposomes.
AB  - Lipid asymmetry is a ubiquitous property of the lipid bilayers in cellular
      membranes and its maintenance and loss play important roles in cell physiology,
      such as blood coagulation and apoptosis. The resulting exposure of
      phosphatidylserine on the outer surface of the plasma membrane has been suggested
      to be caused by a specific membrane enzyme, scramblase, which catalyzes
      phospholipid flip-flop. Despite extensive research the role of scramblase(s) in
      apoptosis has remained elusive. Here, we show that phospholipid flip-flop is
      efficiently enhanced in liposomes by oxidatively modified phosphatidylcholines. A
      combination of fluorescence spectroscopy and molecular dynamics simulations
      reveal that the mechanistic basis for this property of oxidized
      phosphatidylcholines is due to major changes imposed by the oxidized
      phospholipids on the biophysical properties of lipid bilayers, resulting in a
      fast cross bilayer diffusion of membrane phospholipids and loss of lipid
      asymmetry, requiring no scramblase protein.

PMID- 21943417
TI  - KCNE1 and KCNE2 provide a checkpoint governing voltage-gated potassium channel
      alpha-subunit composition.
AB  - Voltage-gated potassium (Kv) currents generated by N-type alpha-subunit
      homotetramers inactivate rapidly because an N-terminal ball domain blocks the
      channel pore after activation. Hence, the inactivation rate of heterotetrameric
      channels comprising both N-type and non-N-type (delayed rectifier) alpha-subunits
      depends upon the number of N-type alpha-subunits in the complex. As Kv channel
      inactivation and inactivation recovery rates regulate cellular excitability, the
      composition and expression of these heterotetrameric complexes are expected to be
      tightly regulated. In a companion article, we showed that the single
      transmembrane segment ancillary (beta) subunits KCNE1 and KCNE2 suppress currents
      generated by homomeric Kv1.4, Kv3.3, and Kv3.4 channels, by trapping them early
      in the secretory pathway. Here, we show that this trapping is prevented by
      coassembly of the N-type alpha-subunits with intra-subfamily delayed rectifier
      alpha-subunits. Extra-subfamily delayed rectifier alpha-subunits, regardless of
      their capacity to interact with KCNE1 and KCNE2, cannot rescue Kv1.4 or Kv3.4
      surface expression unless engineered to interact with them using N-terminal A and
      B domain swapping. The KCNE1/2-enforced checkpoint ensures N-type alpha-subunits
      only reach the cell surface as part of intra-subfamily mixed-alpha complexes,
      thereby governing channel composition, inactivation rate, and-by extension
      cellular excitability.

PMID- 21943419
TI  - Mechanics on myocardium deficient in the N2B region of titin: the cardiac-unique
      spring element improves efficiency of the cardiac cycle.
AB  - Titin (also known as connectin) is an intrasarcomeric muscle protein that
      functions as a molecular spring and generates passive tension upon muscle
      stretch. The N2B element is a cardiac-specific spring element within titin's
      extensible region. Our goal was to study the contribution of the N2B element to
      the mechanical properties of titin, particularly its hypothesized role in
      limiting energy loss during repeated stretch (diastole)-shortening (systole)
      cycles of the heart. We studied energy loss by measuring hysteresis from the area
      between the stretch and release passive force-sarcomere length curves and used
      both wild-type (WT) mice and N2B knockout (KO) mice in which the N2B element has
      been deleted. A range of protocols was used, including those that mimic
      physiological loading conditions. KO mice showed significant increases in
      hysteresis. Most prominently, in tissue that had been preconditioned with a
      physiological stretch-release protocol, hysteresis increased significantly from
      320 +/- 46 pJ/mm(2)/sarcomere in WT to 650 +/- 94 pJ/mm(2)/sarcomere in N2B KO
      myocardium. These results are supported by experiments in which oxidative stress
      was used to mechanically inactivate portions of the N2B-Us of WT titin through
      cysteine cross-linking. Studies on muscle from which the thin filaments had been
      extracted (using the actin severing protein gelsolin) showed that the difference
      in hysteresis between WT and KO tissue cannot be explained by filament sliding
      based viscosity. Instead the results suggest that hysteresis arises from within
      titin and most likely involves unfolding of immunoglobulin-like domains. These
      studies support that the mechanical function of the N2B element of titin includes
      reducing hysteresis and increasing the efficiency of the heart.

PMID- 21943420
TI  - Structural rigidity of paranemic crossover and juxtapose DNA nanostructures.
AB  - Crossover motifs are integral components for designing DNA-based nanostructures
      and nanomechanical devices due to their enhanced rigidity compared to the normal
      B-DNA. Although the structural rigidity of the double helix B-DNA has been
      investigated extensively using both experimental and theoretical tools, to date
      there is no quantitative information about structural rigidity and the mechanical
      strength of parallel crossover DNA motifs. We have used fully atomistic molecular
      dynamics simulations in explicit solvent to get the force-extension curve of
      parallel DNA nanostructures to characterize their mechanical rigidity. In the
      presence of monovalent Na(+) ions, we find that the stretch modulus (gamma(1)) of
      the paranemic crossover and its topoisomer JX DNA structure is significantly
      higher (~30%) compared to normal B-DNA of the same sequence and length. However,
      this is in contrast to the original expectation that these motifs are almost
      twice as rigid compared to the double-stranded B-DNA. When the DNA motif is
      surrounded by a solvent with Mg(2+) counterions, we find an enhanced rigidity
      compared to Na(+) environment due to the electrostatic screening effects arising
      from the divalent nature of Mg(2+) ions. To our knowledge, this is the first
      direct determination of the mechanical strength of these crossover motifs, which
      can be useful for the design of suitable DNA for DNA-based nanostructures and
      nanomechanical devices with improved structural rigidity.

PMID- 21943421
TI  - Unlinking of supercoiled DNA catenanes by type IIA topoisomerases.
AB  - It was found recently that DNA catenanes, formed during replication of circular
      plasmids, become positively (+) supercoiled, and the unlinking of such catenanes
      by type IIA topoisomerases proceeds much more efficiently than the unlinking of
      negatively (-) supercoiled catenanes. In an attempt to explain this striking
      finding we studied, by computer simulation, conformational properties of
      supercoiled DNA catenanes. Although the simulation showed that conformational
      properties of (+) and (-) supercoiled replication catenanes are very different,
      these properties per se do not give any advantage to (+) supercoiled over (-)
      supercoiled DNA catenanes for unlinking. An advantage became evident, however,
      when we took into account the established features of the enzymatic reaction
      catalyzed by the topoisomerases. The enzymes create a sharp DNA bend in the first
      bound DNA segment and allow for the transport of the second segment only from
      inside the bend to its outside. We showed that in (-) supercoiled DNA catenanes
      this protein-bound bent segment becomes nearly inaccessible for segments of the
      other linked DNA molecule, inhibiting the unlinking.

PMID- 21943422
TI  - PAR-3 oligomerization may provide an actin-independent mechanism to maintain
      distinct par protein domains in the early Caenorhabditis elegans embryo.
AB  - Par proteins establish discrete intracellular spatial domains to polarize many
      different cell types. In the single-cell embryo of the nematode worm
      Caenorhabditis elegans, the segregation of Par proteins is crucial for proper
      division and cell fate specification. Actomyosin-based cortical flows drive the
      initial formation of anterior and posterior Par domains, but cortical actin is
      not required for the maintenance of these domains. Here we develop a model of
      interactions between the Par proteins that includes both mutual inhibition and
      PAR-3 oligomerization. We show that this model gives rise to a bistable switch
      mechanism, allowing the Par proteins to occupy distinct anterior and posterior
      domains seen in the early C. elegans embryo, independent of dynamics or
      asymmetries in the actin cortex. The model predicts a sharp loss of cortical Par
      protein asymmetries during gradual depletion of the Par protein PAR-6, and we
      confirm this prediction experimentally. Together, these results suggest both
      mutual inhibition and PAR-3 oligomerization are sufficient to maintain distinct
      Par protein domains in the early C. elegans embryo.

PMID- 21943423
TI  - Folding and homodimerization of wheat germ agglutinin.
AB  - Wheat germ agglutinin (WGA) is emblematic of proteins that specialize in the
      recognition of carbohydrates. It was the first lectin reported to have a capacity
      for discriminating between normal and malignant cells. Since then, it has become
      a preferred model for basic research and is frequently considered in the
      development of biomedical and biotechnological applications. However, the
      molecular basis for the structural stability of this homodimeric lectin remains
      largely unknown, a situation that limits the rational manipulation and
      modification of its function. In this work we performed a thermodynamic
      characterization of WGA folding and self-association processes as a function of
      pH and temperature by using differential scanning and isothermal dilution
      calorimetry. WGA is monomeric at pH 2, and one of its four hevein-like domains is
      unfolded at room temperature. Under such conditions, the agglutinin exhibits a
      fully reversible thermal unfolding that consists of three two-state transitions.
      At higher pH values, the protein forms weak, nonobligate dimers. This behavior
      contrasts with that observed for the other plant lectins studied thus far, which
      form strong, obligate oligomers, indicating a distinctly different molecular
      basis for WGA function. For dimer formation, the four domains must be properly
      folded. Nevertheless, depending on the solution conditions, self-association may
      be coupled with folding of the labile domain. Therefore, dimerization may proceed
      as a rigid-body-like association or a folding-by-binding event. This hybrid
      behavior is not seen in other plant lectins. The emerging molecular picture for
      the WGA assembly highlights the need for a reexamination of existing ligand
      binding data in the literature.

PMID- 21943424
TI  - Relation between molecular shape and the morphology of self-assembling
      aggregates: a simulation study.
AB  - Proteins can aggregate in a wide variety of structures, both compact and
      extended. We present simulations of a coarse-grained anisotropic model that
      reproduce many of the experimentally observed aggregate structures. Conversely,
      all structures predicted by our model have experimental counterparts (ribbons,
      multistranded fibrils, and vesicles). The model we use is that of a rodlike
      particle with an attractive (hydrophobic) stripe on its side. Our Monte Carlo
      simulations show that aggregate morphologies crucially depend on two parameters.
      The first one is the width of the attractive stripe and the second one is a
      presence or absence of attractive interactions at the particle ends. These
      results provide us with a generic insight into the relation between the shape of
      protein-protein interaction potential and the morphology of protein aggregates.

PMID- 21943425
TI  - Enzyme closure and nucleotide binding structurally lock guanylate kinase.
AB  - We investigate the conformational dynamics and mechanical properties of guanylate
      kinase (GK) using a multiscale approach combining high-resolution atomistic
      molecular dynamics and low-resolution Brownian dynamics simulations. The GK
      enzyme is subject to large conformational changes, leading from an open to a
      closed form, which are further influenced by the presence of nucleotides. As
      suggested by recent work on simple coarse-grained models of apo-GK, we primarily
      focus on GK's closure mechanism with the aim to establish a detailed picture of
      the hierarchy and chronology of structural events essential for the enzymatic
      reaction. We have investigated open-versus-closed, apo-versus-holo, and substrate
      versus-product-loaded forms of the GK enzyme. Bound ligands significantly
      modulate the mechanical and dynamical properties of GK and rigidity profiles of
      open and closed states hint at functionally important differences. Our data
      emphasizes the role of magnesium, highlights a water channel permitting active
      site hydration, and reveals a structural lock that stabilizes the closed form of
      the enzyme.

PMID- 21943426
TI  - Multiscale ensemble modeling of intrinsically disordered proteins: p53 N-terminal
      domain.
AB  - Intrinsically disordered proteins (IDPs) are ubiquitous and play key roles in
      transcriptional regulations and other cellular processes. To characterize diverse
      structural ensembles of IDPs, combinations of NMR and computational modeling
      showed some promise, but they need further improvements. Here, for accurate and
      efficient modeling of IDPs, we propose a systematic multiscale computational
      method. We first perform all-atom replica-exchange molecular dynamics (MD)
      simulations of a few fragments selected from a target IDP. These results together
      with generic knowledge-based local potentials are fed into the iterative
      Boltzmann inversion method to obtain an accurate coarse-grained potential. Then
      coarse-grained MD simulations provide the IDP ensemble. We tested the new method
      for the disordered N-terminal domain of p53 showing that the method reproduced
      the residual dipolar coupling and x-ray scattering profile very accurately.
      Further local structure analyses revealed that, guided by all-atom MD ensemble of
      fragments, the p53 N-terminal domain ensemble was biased to kinked structures in
      the AD1 region and biased to extended conformers in a proline-rich region and
      these biases contributed to improvement of the reproduction of the experiments.

PMID- 21943427
TI  - Separating the role of protein restraints and local metal-site interaction
      chemistry in the thermodynamics of a zinc finger protein.
AB  - We express the effective Hamiltonian of an ion-binding site in a protein as a
      combination of the Hamiltonian of the ion-bound site in vacuum and the restraints
      of the protein on the site. The protein restraints are described by the quadratic
      elastic network model. The Hamiltonian of the ion-bound site in vacuum is
      approximated as a generalized Hessian around the minimum energy configuration.
      The resultant of the two quadratic Hamiltonians is cast into a pure quadratic
      form. In the canonical ensemble, the quadratic nature of the resultant
      Hamiltonian allows us to express analytically the excess free energy, enthalpy,
      and entropy of ion binding to the protein. The analytical expressions allow us to
      separate the roles of the dynamic restraints imposed by the protein on the
      binding site and the temperature-independent chemical effects in metal-ligand
      coordination. For the consensus zinc-finger peptide, relative to the aqueous
      phase, the calculated free energy of exchanging Zn(2+) with Fe(2+), Co(2+),
      Ni(2+), and Cd(2+) are in agreement with experiments. The predicted excess
      enthalpy of ion exchange between Zn(2+) and Co(2+) also agrees with the available
      experimental estimate. The free energy of applying the protein restraints reveals
      that relative to Zn(2+), the Co(2+), and Cd(2+)-site clusters are more
      destabilized by the protein restraints. This leads to an experimentally testable
      hypothesis that a tetrahedral metal binding site with minimal protein restraints
      will be less selective for Zn(2+) over Co(2+) and Cd(2+) compared to a zinc
      finger peptide. No appreciable change is expected for Fe(2+) and Ni(2+). The
      framework presented here may prove useful in protein engineering to tune metal
      selectivity.

PMID- 21943428
TI  - Direct measurements of the mechanical stability of zinc-thiolate bonds in
      rubredoxin by single-molecule atomic force microscopy.
AB  - Zinc (Zn) is one of the most abundant metals and is essential for life. Through
      ligand interactions, often with thiolate from cysteine residues in proteins, Zn
      can play important structural roles in organizing protein structure and
      augmenting protein folding and stability. However, it is difficult to separate
      the contributions of Zn-ligand interactions from those originating from intrinsic
      protein folding in experimental studies of Zn-containing metalloproteins, which
      makes the study of Zn-ligand interactions in proteins challenging. Here, we used
      single-molecule force spectroscopy to directly measure the mechanical rupture
      force of the Zn-thiolate bond in Zn-rubredoxin. Our results show that
      considerable force is needed to rupture Zn-thiolate bonds (~170 pN, which is
      significantly higher than the force necessary to rupture the coordination bond
      between Zn and histidines). To our knowledge, our study not only provides new
      information about Zn-thiolate bonds in rubredoxin, it also opens a new avenue for
      studying metal-ligand bonds in proteins using single-molecule force spectroscopy.

PMID- 21943429
TI  - Improvement of structure-based potentials for protein folding by native and
      nonnative hydrogen bonds.
AB  - Pure Go models (where every native interaction equally stabilizes the folded
      state) have widely proved their convenience in the computational investigation of
      protein folding. However, a chemistry-based description of the real interactions
      also provides a desirable tune in the analysis of the folding process, and thus
      some hybrid Go potentials that combine both aspects have been proposed. Among all
      the noncovalent interactions that contribute to protein folding, hydrogen bonds
      are the only ones with a partial covalent character. This feature makes them
      directional and, thus, more difficult to model as part of the coarse-grained
      descriptions that are typically employed in Go models. Thanks to a simplified but
      rigorous representation of backbone hydrogen bonds that we have recently
      proposed, we present in this article a combined potential (Go + backbone hydrogen
      bond) to study the thermodynamics of protein folding in the frame of very simple
      simulation models. We show that the explicit inclusion of hydrogen bonds leads to
      a systematic improvement in the description of protein folding. We discuss a
      representative set of examples (from two-state folders to downhill proteins, with
      different types of native structures) that reveal a relevant agreement with
      experimental data.

PMID- 21943430
TI  - Fibril formation of the rabbit/human/bovine prion proteins.
AB  - Prion diseases are infectious fatal neurodegenerative diseases including
      Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy in
      cattle. The misfolding and conversion of cellular PrP in such mammals into
      pathogenic PrP is believed to be the key procedure. Rabbits are among the few
      mammalian species that exhibit resistance to prion diseases, but little is known
      about the molecular mechanism underlying such resistance. Here, we report that
      the crowding agents Ficoll 70 and dextran 70 have different effects on
      fibrillization of the recombinant full-length PrPs from different species:
      although these agents dramatically promote fibril formation of the proteins from
      human and cow, they significantly inhibit fibrillization of the rabbit protein by
      stabilizing its native state. We also find that fibrils formed by the rabbit
      protein contain less beta-sheet structure and more alpha-helix structure than
      those formed by the proteins from human and cow. In addition, amyloid fibrils
      formed by the rabbit protein do not generate a proteinase K-resistant fragment of
      15-16-kDa, but those formed by the proteins from human and cow generate such
      proteinase K-resistant fragments. Together, these results suggest that the strong
      inhibition of fibrillization of the rabbit PrP by the crowded physiological
      environment and the absence of such a protease-resistant fragment for the rabbit
      protein could be two of the reasons why rabbits are resistant to prion diseases.

PMID- 21943431
TI  - Active-site hydration and water diffusion in cytochrome P450cam: a highly dynamic
      process.
AB  - Long-timescale molecular dynamics simulations (300 ns) are performed on both the
      apo- (i.e., camphor-free) and camphor-bound cytochrome P450cam (CYP101). Water
      diffusion into and out of the protein active site is observed without biased
      sampling methods. During the course of the molecular dynamics simulation, an
      average of 6.4 water molecules is observed in the camphor-binding site of the apo
      form, compared to zero water molecules in the binding site of the substrate-bound
      form, in agreement with the number of water molecules observed in crystal
      structures of the same species. However, as many as 12 water molecules can be
      present at a given time in the camphor-binding region of the active site in the
      case of apo-P450cam, revealing a highly dynamic process for hydration of the
      protein active site, with water molecules exchanging rapidly with the bulk
      solvent. Water molecules are also found to exchange locations frequently inside
      the active site, preferentially clustering in regions surrounding the water
      molecules observed in the crystal structure. Potential-of-mean-force calculations
      identify thermodynamically favored trans-protein pathways for the diffusion of
      water molecules between the protein active site and the bulk solvent. Binding of
      camphor in the active site modifies the free-energy landscape of P450cam channels
      toward favoring the diffusion of water molecules out of the protein active site.

PMID- 21943432
TI  - Nonkinetic modeling of the mechanical unfolding of multimodular proteins: theory
      and experiments.
AB  - We introduce and discuss a novel approach called back-calculation for analyzing
      force spectroscopy experiments on multimodular proteins. The relationship between
      the histograms of the unfolding forces for different peaks, corresponding to a
      different number of not-yet-unfolded protein modules, is exploited in such a
      manner that the sole distribution of the forces for one unfolding peak can be
      used to predict the unfolding forces for other peaks. The scheme is based on a
      bootstrap prediction method and does not rely on any specific kinetic model for
      multimodular unfolding. It is tested and validated in both
      theoretical/computational contexts (based on stochastic simulations) and atomic
      force microscopy experiments on (GB1)(8) multimodular protein constructs. The
      prediction accuracy is so high that the predicted average unfolding forces
      corresponding to each peak for the GB1 construct are within only 5 pN of the
      averaged directly-measured values. Experimental data are also used to illustrate
      how the limitations of standard kinetic models can be aptly circumvented by the
      proposed approach.

PMID- 21943433
TI  - Label-free characterization of cancer-activated fibroblasts using infrared
      spectroscopic imaging.
AB  - Glandular tumors arising in epithelial cells comprise the majority of solid human
      cancers. Glands are supported by stroma, which is activated in the proximity of a
      tumor. Activated stroma is often characterized by the molecular expression of
      alpha-smooth muscle actin (alpha-SMA) within fibroblasts. However, the precise
      spatial and temporal evolution of chemical changes in fibroblasts upon epithelial
      tumor signaling is poorly understood. Here we report a label-free method to
      characterize fibroblast changes by using Fourier transform infrared spectroscopic
      imaging and comparing spectra with alpha-SMA expression in primary normal human
      fibroblasts. We recorded the fibroblast activation process by spectroscopic
      imaging using increasingly tissue-like conditions: 1), stimulation with the
      growth factor TGFbeta1; 2), coculture with MCF-7 human breast cancerous
      epithelial cells in Transwell coculture; and 3), coculture with MCF-7 in three
      dimensional cell culture. Finally, we compared the spectral signatures of stromal
      transformation with normal and malignant human breast tissue biopsies. The
      results indicate that this approach reveals temporally complex spectral changes
      and thus provides a richer assessment than simple molecular imaging based on
      alpha-SMA expression. Some changes are conserved across culture conditions and in
      human tissue, providing a label-free method to monitor stromal transformations.

PMID- 21943434
TI  - Superresolution imaging of multiple fluorescent proteins with highly overlapping
      emission spectra in living cells.
AB  - Localization-based superresolution optical imaging is rapidly gaining popularity,
      yet limited availability of genetically encoded photoactivatable fluorescent
      probes with distinct emission spectra impedes simultaneous visualization of
      multiple molecular species in living cells. We introduce PAmKate, a monomeric
      photoactivatable far-red fluorescent protein, which facilitates simultaneous
      imaging of three photoactivatable proteins in mammalian cells using fluorescence
      photoactivation localization microscopy (FPALM). Successful probe identification
      was achieved by measuring the fluorescence emission intensity in two distinct
      spectral channels spanning only ~100 nm of the visible spectrum. Raft-, non-raft
      , and cytoskeleton-associated proteins were simultaneously imaged in both live
      and fixed fibroblasts coexpressing Dendra2-hemagglutinin, PAmKate-transferrin
      receptor, and PAmCherry1-beta-actin fusion constructs, revealing correlations
      between the membrane proteins and membrane-associated actin structures.

PMID- 21943435
TI  - Detection and imaging of superoxide in roots by an electron spin resonance spin
      probe method.
AB  - The detection, quantification, and imaging of short-lived reactive oxygen
      species, such as superoxide, in live biological specimens have always been
      challenging and controversial. Fluorescence-based methods are nonspecific, and
      electron spin resonance (ESR) spin-trapping methods require high probe
      concentrations and lack the capability for sufficient image resolution. In this
      work, a novel (to our knowledge), sensitive, small ESR imaging resonator was used
      together with a stable spin probe that specifically reacts with superoxide with a
      high reaction rate constant. This ESR spin-probe-based methodology was used to
      examine superoxide generated in a plant root as a result of an apical leaf
      injury. The results show that the spin probe rapidly permeated the plant's
      extracellular space. Upon injury of the plant tissue, superoxide was produced and
      the ESR signal decreased rapidly in the injured parts as well as in the distal
      part of the root. This is attributed to superoxide production and thus provides a
      means of quantifying the level of superoxide in the plant. The spin probe's
      narrow single-line ESR spectrum, together with the sensitive imaging resonator,
      facilitates the quantitative measurement of superoxide in small biological
      samples, such as the plant's root, as well as one-dimensional imaging along the
      length of the root. This type of methodology can be used to resolve many
      questions involving the production of apoplastic superoxide in plant biology.

PMID- 21943436
TI  - In vivo measurement of age-related stiffening in the crystalline lens by
      Brillouin optical microscopy.
AB  - The biophysical and biomechanical properties of the crystalline lens (e.g.,
      viscoelasticity) have long been implicated in accommodation and vision problems,
      such as presbyopia and cataracts. However, it has been difficult to measure such
      parameters noninvasively. Here, we used in vivo Brillouin optical microscopy to
      characterize material acoustic properties at GHz frequency and measure the
      longitudinal elastic moduli of lenses. We obtained three-dimensional elasticity
      maps of the lenses in live mice, which showed biomechanical heterogeneity in the
      cortex and nucleus of the lens with high spatial resolution. An in vivo
      longitudinal study of mice over a period of 2 months revealed a marked age
      related stiffening of the lens nucleus. We found remarkably good correlation (log
      log linear) between the Brillouin elastic modulus and the Young's modulus
      measured by conventional mechanical techniques at low frequencies (~1 Hz). Our
      results suggest that Brillouin microscopy is potentially useful for basic and
      animal research and clinical ophthalmology.

PMID- 21943437
TI  - Development of time-integrated multipoint moment analysis for spatially resolved
      fluctuation spectroscopy with high time resolution.
AB  - Spatial gradients in the behaviors of soluble proteins are thought to underlie
      many phenomena in cell and developmental biology, but the nature and even the
      existence of these gradients are often unclear because few techniques can
      adequately characterize them. Methods with sufficient temporal resolution to
      study the dynamics of diffusing molecules can only sample relatively small
      regions, whereas methods that are capable of imaging larger areas cannot probe
      fast timescales. To overcome these limitations, we developed and implemented time
      integrated multipoint moment analysis (TIMMA), a form of fluorescence fluctuation
      spectroscopy that is capable of probing timescales down to 20 MUs at hundreds of
      different locations simultaneously in a sample. We show that TIMMA can be used to
      measure the diffusion of small-molecule dyes and fluorescent colloids, and that
      it can create spatial maps of the behavior of soluble fluorescent proteins
      throughout mammalian tissue culture cells. We also demonstrate that TIMMA can
      characterize internal gradients in the diffusion of freely moving proteins in
      single cells.

PMID- 21943438
TI  - Retraction. Fluorescence spectroscopy of conformational changes of single LH2
      complexes.

PMID- 21943439
TI  - Rigidity sensing explained by active matter theory.
AB  - The magnitude of traction forces exerted by living animal cells on their
      environment is a monotonically increasing and approximately sigmoidal function of
      the stiffness of the external medium. We rationalize this observation using
      active matter theory, and propose that adaptation to substrate rigidity results
      from an interplay between passive elasticity and active contractility.

PMID- 21943440
TI  - Germ cell tumour: late recurrence after 43 years.
AB  - We report the late relapse of a patient following 43 years of surveillance of a
      germ cell tumour, thought to be a pure seminoma, having undergone yolk sac
      differentiation. The longest previous recorded time to relapse was 32 years
      (malignant teratoma with adenocarcinoma de-differentiation).(1) This case report
      demonstrates a late relapse of a testicular germ cell tumour is possible whatever
      the initial stage. European Association of Urology guidelines state close and
      active follow-up is mandatory for at least five years' surveillance due to the
      high and often late rate of relapse. Furthermore, they also suggest continuing
      follow-up although it is unclear as to how long this should last.(7)

PMID- 21943441
TI  - Pressure necrosis secondary to negative pressure dressing.
AB  - Wound complications in patients with significant co-morbidities is common;
      however, in our patient the problem was compounded by the inappropriate placement
      of negative pressure dressing.

PMID- 21943443
TI  - Pancreaticogastric fistula secondary to intraductal papillary mucinous neoplasia:
      a case report and review of the literature.
AB  - Intraductal papillary mucinous neoplasms (IPMNs) are benign cystic lesions of the
      pancreas with recognised premalignant potential. An occasional feature of IPMNs
      is fistula formation to surrounding organs. This report describes a case of a
      pancreaticogastric fistula from a main duct  IPMN that produced the complete
      resolution of the patient's symptoms.

PMID- 21943442
TI  - Isolated gallbladder perforation following blunt abdominal trauma in a six-year
      old child.
AB  - Isolated perforation of the gallbladder secondary to blunt trauma is rare.
      Furthermore, only a few cases exist in the infant age group. It has vague
      symptoms and interpretation of the radiology imaging is challenging. Diagnosis is
      usually made at operation. We report the case of a six-year-old boy who fell on
      to the handlebars of his scooter, sustaining an isolated gallbladder perforation.
      The authors highlight the importance of interpreting the volume of
      intraperitoneal fluid and early diagnostic laparoscopy.

PMID- 21943444
TI  - Alveolar soft part sarcoma causing perianal abscess.
AB  - A 34-year-old woman presented with a perianal abscess that communicated with the
      vagina. There was a background of a one-year history of a conservatively treated,
      traumatic, paravaginal haematoma. Histology of the fistula tract showed alveolar
      soft part sarcoma and subsequent imaging  identified a large soft tissue mass in
      the pelvis with lung metastases. Alveolar soft part sarcoma is a rare soft tissue
      sarcoma of unknown cellular origin affecting predominantly young women, often in
      deep soft tissues and lower extremities.

PMID- 21943445
TI  - Swelling in the upper arm: the presentation and management of an isolated
      brachial artery aneurysm.
AB  - True aneurysms of the brachial artery are uncommon. We describe the presentation
      and surgical management of an isolated, brachial artery aneurysm in a 64-year-old
      woman. Excision of the aneurysm and long saphenous venous interposition grafting
      was performed with no postoperative complications  and histology demonstrated
      true aneurysmal degeneration.

PMID- 21943446
TI  - Sclerosing encapsulating peritonitis secondary to dermoid cyst rupture: a case
      report.
AB  - This case report documents the presentation and management of a 26-year-old
      female patient diagnosed with SEP secondary to dermoid cyst rupture. The authors
      postulate that acute chemical peritonitis secondary to dermoid cyst rupture can
      develop into SEP resulting in the clinical features  depicted in this case
      report.

PMID- 21943447
TI  - Conservative surgery in the management of a benign ovarian cystic teratoma
      presenting as a rectal mass: a case report.
AB  - Ovarian cystic teratomas constitute 10-15% of all ovarian tumours and are the
      most common ovarian neoplasms found in adolescence and during pregnancy.
      Nevertheless, ovarian cystic teratomas have also been described in patients aged
      1-91 years. We report an unusual case of a benign  ovarian cystic teratoma
      presenting as a rectal mass that was managed surgically using radical resection
      by a multidisciplinary team. This case report highlights the importance of
      preoperative investigations including colonoscopy and radiological
      investigations. A dedicated pelvic radiologist/pathologist  and the involvement
      of a multidisciplinary team at the time of initial diagnosis and a gynaecologist
      and colorectal surgeon at the time of surgery will lead to an accurate diagnosis
      and the most appropriate treatment. Although rare, erosion of an ovarian dermoid
      into the rectum should be considered  in young women who have an atypical
      presentation and are found to have a lesion in the rectum with biopsies
      indicating benign pathology.

PMID- 21943448
TI  - Synchronous gastric and colonic metastases of invasive lobular breast carcinoma:
      case report and review of the literature.
AB  - Breast cancer is the most common malignancy in women and the main cause of cancer
      death in the UK. Gastrointestinal (GI) tract metastasis and carcinomatosis from
      primary breast cancer are rare but breast cancer is the second most common
      primary malignancy to metastasise to the GI tract  after malignant melanoma. The
      metastatic patterns of invasive lobular carcinoma (ILC) and invasive ductal
      carcinoma (IDC) have been shown to differ considerably. Liver, lung and brain
      metastases are more common in IDC. Most series report a greater prediliction for
      lobular carcinoma to metastasise  to the GI tract, gynaecological organs or
      peritoneum.  The presentation of GI metastasis due to breast cancer is typically
      vague and the clinical, radiological, endoscopic and histopathologic findings are
      often difficult to distinguish from primary gastric carcinoma. Such a patient is
      more  likely to present to a luminal surgeon or gastroenterologist than a breast
      surgeon. Therefore a high index of clinical suspicion with early endoscopy in
      those with non-specific symptoms and a past history of breast cancer,
      particularly ILC, are recommended.  It is imperative to differentiate  between
      metastatic breast cancer and primary gastric carcinoma as treatment strategies
      differ hugely. Therefore, correlation of endoscopic biopsy histology with the
      primary breast cancer histology is essential. Treatment modalities are limited to
      appropriate systemic therapy, which may have  a palliative effect in up to 50%.
      Surgical intervention is nearly always limited to palliative bypass only.
      Prognosis is consistent with the median survival of all women with metastatic
      disease secondary to breast cancer.

PMID- 21943449
TI  - Testicular pain as a presentation of Cowden syndrome.
AB  - This case report outlines a rare case in Cowden syndrome and PTEN (phosphatase
      and tensin homolog) gene mutation and how it may initially present to the
      urologist. Also known as multiple hamartoma syndrome, Cowden syndrome is a rare
      disorder associated with the development of several  types of malignancy. A
      thorough search of the literature reveals limited information regarding its
      presentation to the urologist. We report the case of a 47-year-old gentleman with
      a two-week history of worsening pain and swelling in his left testicle.
      Testicular ultrasound revealed multiple  hyperechoic areas bilaterally suggestive
      of multiple lipomas. He was also found to have macrocephaly, freckling of his
      glans and foreskin and an enlarged nodular goitre and the geneticist diagnosed
      Cowden syndrome. The disease is discussed and guidance is given on its management
      and follow  up.

PMID- 21943450
TI  - Bilateral ischaemic optic neuropathy following laparoscopic proctocolectomy: a
      case report.
AB  - INTRODUCTION: Perioperative visual loss occurring during non-ocular surgery is a
      devastating event. Ischaemic optic neuropathy (ION) is a complication described
      following many procedures. We report the first case of ION occurring during
      laparoscopic proctocolectomy and discuss the aetiological factors. CASE HISTORY:
      A 58-year-old male presented with rectal bleeding and was diagnosed with an
      adenocarcinoma of the sigmoid colon. A very difficult laparoscopic sigmoidectomy
      and a low anterior resection of the rectum with an end colostomy were carried
      out. The technical difficulties were due to body habitus and the size and
      position of the tumour. The operation lasted over six hours. On the first day
      postoperatively, the patient complained of blurred vision. Examination showed
      that he had suffered bilateral ION. DISCUSSION: Despite the growing numbers of
      laparoscopic operations, ION has rarely been described. The cases that were
      published involved laparoscopic prostatectomy and a prolonged steep Trendelenburg
      position. We postulate that the patient presented here had suffered both from a
      relative hypotension and from an acute rise in the intraorbital pressure due to
      patient position, both factors combining to cause a disruption to ocular
      perfusion resulting in ION with severe permanent visual damage.

PMID- 21943451
TI  - A new recreational mechanism for the boxer's knuckle: cause for concern?
AB  - Traumatic injuries of the metacarpophalangeal joints are a common occurrence in
      professional and recreational sports such as boxing and martial arts, especially
      the fourth and fifth metacarpals. Injury usually results from a forceful impact
      with a clenched fist. The spectrum of injuries  varies from simple skin
      laceration to extensor mechanism disruption, dorsal capsule rupture, metacarpal
      fractures and carpometacarpal joint injuries. These injuries are well documented
      in boxers as well as in patients who had been involved in fights and assaults. We
      report on two patients  sustaining similar injuries to the dorsum of the hand but
      following punching of a recreational 'punching machine'. We describe the patterns
      of injury encountered and summarise the treatment. For clinical and safety
      reasons as well as the potential medicolegal implications, we believe it is 
      important to highlight this mechanism of injury.

PMID- 21943453
TI  - Breathtaking obesity?

PMID- 21943454
TI  - Management of frozen shoulder - conservative vs surgical?

PMID- 21943455
TI  - The use and effectiveness of cadaveric workshops in higher surgical training: a
      systematic review.
AB  - INTRODUCTION: The aim of this systematic review is to describe the use of
      cadavers in postgraduate surgical training, to determine the effect of cadaveric
      training sessions on surgical trainees' technical skills performance and to
      determine how trainees perceive the use of cadaveric workshops as a training
      tool. METHODS: An electronic literature search was performed, restricted to the
      English language, of MEDLINE((r)), EmbaseTM, the Cumulative Index to Nursing and
      Allied Health Literature (CINAHL((r))), Centre for Agricultural Bioscience (CAB)
      Abstracts, the Educational Resources Information Center (ERICTM) database, the
      British Education Index, the Australian Education Index, the Cochrane Library and
      the Best Evidence in Medical Education website. Studies that were eligible for
      review included primary studies evaluating the use of human cadaveric surgical
      workshops for surgical skills training in postgraduate surgical trainees and
      those that included a formal assessment of skills performance or trainee
      satisfaction after the training session. RESULTS: Eight studies were identified
      as satisfying the eligibility criteria. One study showed a benefit from cadaveric
      workshop training with regard to the ability of trainees to perform relatively
      simple emergency procedures and one showed weak evidence of a benefit in
      performing more complex surgical procedures. Three studies showed that trainees
      valued the experience of cadaveric training. CONCLUSIONS: Evidence for the
      effectiveness of cadaveric workshops in surgical training is currently limited.
      In particular, there is little research into how these workshops improve the
      performance of surgical trainees during subsequent live surgery. However, both
      trainees and assessors hold them in high regard and feel they help to improve
      operative skills. Further research into the role of cadaveric workshops is
      required.

PMID- 21943456
TI  - Peritonsillar abscess after tonsillectomy: a review of the literature.
AB  - INTRODUCTION: Peritonsillar abscess (PTA) is a common condition with a
      complicated aetiology. PTA after tonsillectomy is rare. This literature review of
      PTA in the absence of tonsil tissue aims to collate experience of these cases and
      examine the wider implications for understanding the aetiology of PTA formation.
      METHODS: A structured literature review was performed using Ovid MEDLINE(r).
      Keywords 'quinsy' or 'peritonsillar abscess' were combined with 'tonsillectomy'.
      RESULTS: The search resulted in 212 citations and the identification of 11 cases
      of PTA formation in the absence of tonsil tissue. The most common indication for
      tonsillectomy was recurrent tonsillitis or PTA. Nine patients had no interval
      peritonsillar infection (ie a peritonsillar infection after a tonsillectomy)
      prior to presenting with the PTA. The mean interval between tonsillectomy and PTA
      was 16 years. All patients were managed either by incision and drainage or by
      needle aspiration with or without antibiotics. CONCLUSIONS: PTA in the absence of
      tonsil tissue is rare. Potential sources of infection include congenital
      branchial fistulas, Weber's glands and dental disease. These alternatives should
      also be considered in patients presenting with PTA formation in the absence of
      concurrent tonsillitis and may influence management decisions.

PMID- 21943457
TI  - Pancreatic and peripancreatic somatostatinomas.
AB  - BACKGROUND: Somatostatinomas are rare neuroendocrine tumours with an annual
      incidence of 1 in 40 million. They arise in the pancreas or periampullary
      duodenum. Most are clinically non-secretory and do not cause the somatostatinoma
      syndrome. Many are metastatic at presentation and their management is typically
      multimodal. CASE HISTORIES: Four cases of somatostatinoma are described. Two
      patients with periampullary disease presented with biliary obstruction, one with
      frank jaundice and one with incidental bile duct obstruction on investigation of
      hepatitis B. Each patient had type 1 neurofibromatosis and resection of the
      somatostatinoma by means of a pylorus-preserving proximal pancreaticoduodenectomy
      has resulted in long-term survival. Another two patients with metastatic
      pancreatic somatostatinomas presented with abdominal pain. Contrasting management
      illustrates current treatment strategies that are dependent in part on the
      distribution of the disease. DISCUSSION: The pathophysiology, presentation,
      clinical associations and role of diagnostic imaging are discussed for
      periampullary and pancreatic neuroendocrine tumours. Operative treatment has an
      important role in both the curative and palliative settings in conjunction with
      appropriate medical treatments and these are described. Management options depend
      on the extent of the disease and the cases are used to illustrate the rationale
      of such strategies.

PMID- 21943458
TI  - Do sonographic and cytological features predict malignancy in cytologically
      indeterminate thyroid nodules?
AB  - INTRODUCTION: The current algorithm for managing patients with indeterminate
      (Thy3) thyroid cytology is a thyroid lobectomy followed by a completion
      thyroidectomy depending on histology. We investigated whether sonographic and or
      cytological features in addition to clinical characteristics would predict the
      potential for malignancy in a cohort of patients with thyroid nodules of
      indeterminate cytology. METHODS: Perusing a clinical database of all patients
      undergoing ultrasonography guided fine needle aspiration (FNA) of thyroid
      nodules, we identified all Thy3 lesions. The demographic, ultrasonography and
      cytological details of benign and malignant groups were compared by t-test, chi
      square test and, when appropriate, Fisher's exact test. Association between
      studied characteristics and malignancy was tested by binary logistic regression
      using single input. A p-value of <0.05 was considered significant. RESULTS:
      During the retrospective study period of January 2003 to July 2010, a total of
      1,019 patients underwent FNA, of which 69 (6.8%) were classed as Thy3. Of these,
      59 underwent surgical treatment and the histological outcomes were grouped as
      benign (n=42, 71.2%) and malignant (n=17, 28.8%). These groups were analysed for
      the predictive variables. Age, sex and sonological characters were similar in the
      two groups (p>0.05). The two microcalcifications observed were both in the
      malignant group. Among all the variables assessed, only the absence of normal
      follicular cells was associated with malignant nodules (univariate analysis,
      p=0.034). CONCLUSIONS: Malignancy was more common in Thy3 patients with an
      absence of normal follicular cells and such patients may therefore warrant a
      total thyroidectomy.

PMID- 21943459
TI  - Decisions to operate: the ASA grade 5 dilemma.
AB  - INTRODUCTION: Deciding to operate on high risk patients suffering catastrophic
      surgical emergencies can be problematic. Patients are frequently classed as
      American Society of Anesthesiologists (ASA) grade 5 and, as a result, aggressive
      but potentially lifesaving intervention is withheld. The aim of our study was to
      review the short-term outcomes in patients who were classed as ASA grade 5 but
      subsequently underwent surgery despite this and to compare the ASA scoring model
      to other predictors of surgical outcome. METHODS: All patients undergoing
      emergency surgery with an ASA grade of 5 were identified. Patient demographics,
      indications for surgery, intraoperative findings and outcomes were recorded. In
      addition to the ASA scores, retrospective Portsmouth Physiological and Operative
      Severity Score for the enUmeration of Mortality and morbidity (P POSSUM) and
      Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were
      calculated and compared to the observed outcomes. RESULTS: Nine patients (39%)
      survived to discharge. ASA grade was a poor predictor of outcome. P POSSUM and
      APACHE II scores correlated significantly with each other and with observed
      outcomes when predicting surgical mortality. The median stay for survivors in the
      intensive care unit was nine days. CONCLUSIONS: In times of an ageing population,
      the number of patients suffering catastrophic surgical events will increase.
      Intervention, with little hope of a cure, a return to independent living or an
      acceptable quality of life, leads to unnecessary end-of-life suffering for
      patients and their relatives, and consumes sparse resources. The accuracy and
      reliability of ASA grade 5 as an outcome predictor has been questioned. P POSSUM
      and APACHE II scoring systems are significantly better predictors of outcome and
      should be used more frequently to aid surgical decision-making in high risk
      patients.

PMID- 21943460
TI  - Prophylaxis of venous thromboembolism in general surgery: guidelines differ and
      we still need local policies.
AB  - INTRODUCTION: Venous thromboembolism (VTE) prophylaxis has become a major issue
      for surgeons both in the UK and worldwide. Several different sources of guidance
      on VTE prophylaxis are available but these differ in design and detail. METHODS:
      Two similar audits were performed, one year apart, on the VTE prophylaxis
      prescribed for all general surgical inpatients during a single week (90 patients
      and 101 patients). Classification of patients into different risk groups and
      compliance in prescribing prophylaxis were examined using different
      international, national and local guidelines. RESULTS: There were significant
      differences between the numbers of patients in high, moderate and low-risk groups
      according to the different guidelines. When groups were combined to indicate
      simply 'at risk' or 'not at risk' (in the manner of one of the guidelines), then
      differences were not significant. Our compliance improved from the first audit to
      the second. Patients at high risk received VTE prophylaxis according to guidance
      more consistently than those at low risk. CONCLUSIONS: Differences in guidance on
      VTE prophylaxis can affect compliance significantly when auditing practice,
      depending on the choice of 'gold standard'. National guidance does not remove the
      need for clear and detailed local policies. Making decisions about policies for
      lower-risk patients can be more difficult than for those at high risk.

PMID- 21943461
TI  - Rectus abdominis myocutaneous flaps for perineal reconstruction: modifications to
      the technique based on a large single-centre experience.
AB  - INTRODUCTION: Perineal wound breakdown with delayed wound healing represents a
      significant cause of morbidity following surgery and radiotherapy to the
      perineum. The rectus abdominis myocutaneous (RAM) flap has been used increasingly
      to reconstruct the perineum with good effect. We describe our six-year experience
      of reconstruction of the perineum with the RAM flap and share some surgical
      adjuncts we believe are useful. METHODS: We conducted a retrospective case note
      review of all patients who underwent a reconstruction of the perineum using the
      RAM flap between August 2003 and October 2009. Indications for the flap,
      complication rates and outcomes were all observed. RESULTS: We conducted 16 RAM
      flap procedures, 15 of which (94%) were primary repairs and 1 (6%) a secondary
      repair. Three (19%) developed donor site hernias, two (12.5%) developed minor
      perineal wound infections, eight (50%) developed minor perineal wound breakdown
      and in one (6%) flap failure was observed. No perineal hernias were observed.
      There were no surgical mortalities. CONCLUSIONS: The RAM flap has a high success
      rate and an acceptable morbidity rate and is a useful tool in the reconstruction
      of complex perineal wounds. Modifications to the standard surgical technique may
      reduce complications and improve the versatility of this flap.

PMID- 21943462
TI  - A single institution experience with skin sparing mastectomy and immediate breast
      reconstruction.
AB  - INTRODUCTION: Skin sparing mastectomies (SSMs) represent a surgical approach that
      preserves the natural skin envelope of the breast and, when combined with
      immediate reconstruction, offers a good cosmetic outcome. The aim of this
      retrospective study was to compare the risk of local recurrence (LR) in this
      series with the known rate of recurrence following a conventional mastectomy.
      METHODS: A total of 108 patients with breast cancer who underwent an SSM and
      immediate breast reconstruction over a 6-year period were reviewed. RESULTS: A
      follow-up of more than eight years showed that three patients (2.78%) had
      developed LR. CONCLUSIONS: The rate of LR is low with SSMs and is comparable to
      that seen with conventional mastectomies.

PMID- 21943463
TI  - The influence of clinicopathological features on the predictive accuracy of
      conventional breast imaging in determining the extent of screen-detected high
      grade pure ductal carcinoma in situ.
AB  - INTRODUCTION: The extent of calcified ductal carcinoma in situ (DCIS) detected by
      screening mammography is a determinant for treatment with breast conserving
      surgery (BCS). However, DCIS may be uncalcified and almost a quarter of patients
      with DCIS treated initially by BCS either require a second operation or are found
      to have unexpected invasive disease following surgery. Identification of these
      cases might guide selective implementation of additional diagnostic procedures.
      METHODS: A retrospective review of patients with a preoperative diagnosis of pure
      high-grade DCIS at the Southampton and Salisbury Breast Screening Unit over a ten
      year period was carried out. Mammograms were reviewed independently by a
      consultant radiologist and additional factors including the Breast Imaging
      Reporting and Data System (BI-RADS((r))) breast density score, DCIS extent and
      disease location within the breast recorded. RESULTS: Unexpected invasive disease
      was found in 35 of 144 patients (24%). Within our unit the re-excision rate for
      all screen-detected DCIS is currently 23% but for patients included in this study
      with high-grade DCIS the re-excision rate was 39% (34/87). The extent of DCIS
      (p=0.008) and lack of expression of the oestrogen receptor (ER) predicted the
      requirement for re-excision in both univariate (p=0.004) and multivariate
      analysis (p=0.005). CONCLUSIONS: High-grade DCIS may be focally uncalcified,
      leading to underestimation of disease extent, which might be related to ER
      status. Invasive foci associated with high-grade DCIS are often mammographically
      occult. Exploration of additional biomarkers and targeted use of further
      diagnostic techniques may improve the preoperative staging of DCIS.

PMID- 21943464
TI  - Native nephrectomy in transplant patients with autosomal dominant polycystic
      kidney disease.
AB  - INTRODUCTION: This study examined the clinical indications and timing for native
      nephrectomy (NN), together with the associated pathological findings in
      transplant patients with autosomal dominant polycystic kidney disease (ADPKD) at
      our institute over a period of 20 years. METHODS: A retrospective review was
      performed of ADPKD patients who had undergone both kidney transplantation and NN.
      Patients were identified from the kidney transplant database between 1988 and
      2008 at Guy's and St Thomas' Hospital and the notes reviewed. All NN specimens
      were re-reviewed and reported according to current guidelines. RESULTS: There
      were 157 kidney transplants performed for ADPKD (114 cadaveric and 43 living
      donor). Of these, 31 required NN (28 bilateral). The timing of NN was pre
      transplant in 10 cases, at the time of the transplant in 1 case and post
      transplant in 20 cases. The indications for NN were urinary tract infection
      (n=14, 45%), pain (n=12, 39%), tumour suspicion (n=3, 10%), haematuria (n=1, 3%)
      and space (n=1, 3%). Mortality in this NN series was 3%, with a 65% surgical
      morbidity rate. The length of hospital stay post-NN was significantly longer with
      open compared with laparoscopic techniques (p=0.003). There were two renal cell
      carcinomas (RCCs) in this series. Both patients presented with macroscopic
      haematuria (bilateral pT1a papillary RCCs in one case and a pT3b clear cell RCC
      in the other case). The incidence of RCC in this series of ADPKD transplant
      patients was 1.3%. CONCLUSIONS: We have demonstrated that the majority of ADPKD
      patients do not require NN, with only 20% of our series undergoing this
      procedure. The timing of NN is variable and dictated by indication. NN was only
      required to make space for transplantation in one case (combined kidney and
      pancreas transplant). The main indications for NN were recurrent infection and
      pain, where NN can provide a successful outcome. Laparoscopic NN can be performed
      safely in patients with ADPKD. Haematuria in such patients should not be assumed
      to be of benign origin and requires exclusion of urinary tract malignancy as the
      incidence of RCC in this population is at least as common as in the general
      population.

PMID- 21943465
TI  - Intraoperative cell salvage versus postoperative autologous blood transfusion in
      hip arthroplasty: a retrospective service evaluation.
AB  - INTRODUCTION: A number of ways of reducing blood loss in arthroplasty have been
      explored, including preoperative autologous transfusion, intraoperative cell
      salvage and postoperative autologous transfusions. Both intraoperative blood
      salvage and postoperative retransfusion drains have been shown to be effective in
      reducing blood loss in total hip arthroplasty. In our department there was a
      change in practice from using postoperative retransfusion drains to
      intraoperative cell salvage. To our knowledge no study has directly compared
      using intraoperative blood salvage and postoperative retransfusion drains alone
      in total hip arthroplasty. METHODS: This was a retrospective service evaluation
      including all primary hip arthroplasty performed under our care between January
      2006 and December 2008. Patients were divided into two groups: Group A used a
      postoperative autologous blood transfusion (ABT) drain and Group B used
      intraoperative cell salvage. RESULTS: A total of 144 patients were included in
      this study: 84 in Group A and 60 in Group B. The mean haemoglobin difference for
      Group A was 3.96g/dl (standard deviation [SD]: 1.52) and for Group B it was
      3.46g/dl (SD: 1.42). The mean haematocrit difference for Group A was 0.12% (SD:
      0.05) and for Group B it was 0.10% (SD: 0.04). Using an independent t-test for
      the comparison of means, a significant difference was found between Group A and B
      both in regards to haemoglobin difference (p=0.009) and haematocrit difference
      (p=0.046). CONCLUSIONS: We feel that intraoperative cell salvage provides a more
      efficient method of reducing blood loss than postoperative retransfusion in
      primary total hip replacement. A prospective randomised study would be useful to
      ascertain any clinical difference between the two methods.

PMID- 21943466
TI  - Patients' misunderstanding of common orthopaedic terminology: the need for
      clarity.
AB  - INTRODUCTION: Patients' understanding of their medical problems is essential to
      allow them to make competent decisions, comply with treatment and enable
      recovery. We investigated patients' understanding of orthopaedic terms to
      identify those words surgeons should make the most effort to explain. METHODS:
      This questionnaire-based study recruited patients attending the orthopaedic
      clinics. Qualitative and quantitative data were collected using free text boxes
      for the patients' written definitions and multiple choice questions (MCQs).
      RESULTS: A total of 133 patients took part. Of these, 74% identified English as
      their first language. 'Broken bone' was correctly defined by 71% of respondents
      whereas 'fractured bone' was only correctly defined by 33%. 'Sprain' was
      correctly defined by 17% of respondents, with 29% being almost correct, 25% wrong
      and 29% unsure. In the MCQs, 51% of respondents answered correctly for
      'fracture', 55% for 'arthroscopy', 46% for 'meniscus', 35% for 'tendon' and 23%
      for 'ligament'. 'Sprained' caused confusion, with only 11% of patients answering
      correctly. Speaking English as a second language was a significant predictive
      factor for patients who had difficulty with definitions. There was no significant
      variation among different age groups. CONCLUSIONS: Care should be taken by
      surgeons when using basic and common orthopaedic terminology in order to avoid
      misunderstanding. Educating patients in clinic is a routine part of practice.

PMID- 21943467
TI  - Ultrasonography aids decision-making in children with abdominal pain.
AB  - INTRODUCTION: Although regular clinical assessment of the acute abdomen is
      considered best practice, ultrasonography confirming the presence of appendicitis
      will add to the decision-making process. The aim of this study was to assess the
      accuracy of ultrasonography and its usefulness in diagnosing acute appendicitis
      in a regional paediatric surgical institution. METHODS: Retrospectively and in
      this order, radiology, theatre and histopathology databases were searched for
      patients who had presented with acute abdominal pain, patients who had undergone
      an appendicectomy and all appendix specimens over a two-year period. The
      databases were cross-referenced against each other. RESULTS: A total of 273 non
      incidental appendicectomies were performed over the study period. The negative
      appendicectomy rate was 16.5% and the perforation rate 23.7%. Thirty-nine per
      cent of children undergoing an appendicectomy had at least one pre-operative
      ultrasound scan. Ultrasonography as a diagnostic tool for acute appendicitis in
      children had a sensitivity of 83.3%, a specificity of 97.4%, a positive
      predictive value of 92.1% and a negative predictive value of 94.0%. CONCLUSIONS:
      Ultrasonography is used liberally to aid in the decision making process of
      equivocal and complicated cases of acute appendicitis and it achieves good
      measures of accuracy. As a diagnostic tool it is unique in its ability to
      positively predict as well as exclude. A high negative predictive value suggests
      that more patients could be managed on an outpatient basis following a negative
      scan.

PMID- 21943469
TI  - Editorial: Differences in technique between different disciplines: a lesson in
      sharing evidence.

PMID- 21943470
TI  - Ultrasound mapping of long saphenous vein surface anatomy in coronary artery
      bypass surgery.

PMID- 21943471
TI  - Use of a purse string suture in proximal coronary anastomosis to reduce size
      mismatch between conduit and aortotomy.

PMID- 21943472
TI  - Use of a femoral impaction grafting system in revision total elbow arthroplasty.

PMID- 21943473
TI  - The use of an oxygen cylinder key for removal of a Hoffmann II external fixator.

PMID- 21943474
TI  - 'Omental wrap': a simple technique to close the mesenteric defect after
      laparoscopic right hemicolectomy.

PMID- 21943475
TI  - Femoral intramedullary biopsy: improving tissue sampling.

PMID- 21943476
TI  - Risk-free gastrostomy tube exchange.

PMID- 21943477
TI  - A simple technique to achieve effective irrigation at the end of an arthroscopy.

PMID- 21943478
TI  - Incisions for vascular clamps in minimal access aortic surgery.

PMID- 21943479
TI  - The unequal surgical wound.

PMID- 21943480
TI  - The modified recovery position for posterior leg surgery.

PMID- 21943481
TI  - A simple technique to maximise eye protection for surgeons with prescription
      glasses.

PMID- 21943482
TI  - The ACCOMPLISH study. A cluster randomised trial on the cost-effectiveness of a
      multicomponent intervention to improve hand hygiene compliance and reduce
      healthcare associated infections.
AB  - BACKGROUND: Public health authorities have recognized lack of hand hygiene in
      hospitals as one of the important causes of preventable mortality and morbidity
      at population level. The implementation strategy ACCOMPLISH (Actively Creating
      COMPLIance Saving Health) targets both individual and environmental determinants
      of hand hygiene. This study aims to evaluate the cost-effectiveness of a
      multicomponent implementation strategy aimed at the reduction of healthcare
      associated infections in Dutch hospital care, by promotion of hand hygiene.
      METHODS/DESIGN: The ACCOMPLISH package will be evaluated in a two-arm cluster
      randomised trial in 16 hospitals in the Netherlands, in one intensive care unit
      and one surgical ward per hospital. INTERVENTION: A multicomponent package,
      including e-learning, team training, introduction of electronic alcohol based
      hand rub dispensers and performance feedback. VARIABLES: The primary outcome
      measure will be the observed hand hygiene compliance rate, measured at baseline
      and after 6, 12 and 18 months; as a secondary outcome measure the prevalence of
      healthcare associated infections will be measured at the same time points.
      Process indicators of the intervention will be collected pre and post
      intervention. An ex-post economic evaluation of the ACCOMPLISH package from a
      healthcare perspective will be performed. STATISTICAL ANALYSIS: Multilevel
      analysis, using mixed linear modelling techniques will be conducted to assess the
      effect of the intervention strategy on the overall compliance rate among
      healthcare workers and on prevalence of healthcare associated infections.
      Questionnaires on process indicators will be analysed with multivariable linear
      regression, and will include both behavioural determinants and determinants of
      innovation. Cost-effectiveness will be assessed by calculating the incremental
      cost-effectiveness ratio, defined here as the costs for the intervention divided
      by the difference in prevalence of healthcare associated infections between the
      intervention and control group. DISCUSSION: This study is the first RCT to
      investigate the effects of a hand hygiene intervention programme on the number of
      healthcare associated infections, and the first to investigate the cost
      effectiveness of such an intervention. In addition, if the ACCOMPLISH package
      proves successful in improving hand hygiene compliance and lowering the
      prevalence of healthcare associated infections, the package could be disseminated
      at (inter)national level. TRIAL REGISTRATION: NTR2448.

PMID- 21943484
TI  - Regulatory T cells GATA have it.
AB  - The factors that control regulatory T (Treg) cell homeostasis and function are
      still being defined. In this issue of Immunity, Wang et al. (2011) demonstrate
      that the Th2 cell-associated transcription factor GATA-3 helps control Foxp3
      expression in Treg cells and is required for their proper functional activity in
      vivo.

PMID- 21943483
TI  - Double primary malignancies associated with colon cancer in patients with situs
      inversus totalis: two case reports.
AB  - Situs inversus totalis (SIT) is not itself a premalignant condition, however,
      rare synchronous or metachronous multiple primary malignancies have been
      reported. Herein we present a case of synchronous transverse and sigmoid colon
      cancers and a case of metachronous rectosigmoid colon and gastric cancers in
      patients with SIT.A 66-year-old male with SIT was referred for a two-month
      history of hematochezia. Synchronous colonic tumors were found on the proximal
      transverse and sigmoid colon. The patient underwent open total colectomy and was
      discharged without incident. A 71-year-old female with rectosigmoid colon cancer
      and SIT underwent laparoscopy-assisted low anterior resection. Fourteen months
      after the surgery, the patient developed a single hepatic metastasis and
      underwent hepatic segmentectomy (S6). Forty-six months after laparoscopy-assisted
      low anterior resection, the patient developed metachronous early gastric cancer
      on the antrum and underwent radical subtotal gastrectomy with gastroduodenostomy.
      The patient is doing well without recurrence for 28 months.

PMID- 21943485
TI  - Excitable T cells: Ca(v)1.4 channel contributions and controversies.
AB  - Store-operated CRAC channels encoded by the Orai genes mediate calcium entry in T
      cells. In this issue of Immunity, Omilusik et al. (2011) record Ca(V)1.4-mediated
      voltage-gated calcium currents in T cells and address their role for T cell
      development and function.

PMID- 21943486
TI  - Nanocluster formation: more with memory.
AB  - The molecular basis of quicker and stronger responses by memory T cells is
      elusive. In this issue of Immunity, Kumar et al. (2011) demonstrate that more T
      cell receptor nanoclusters are present on memory cells than naive T cells before
      antigen stimulation, suggesting a basis for quick memory response.

PMID- 21943487
TI  - Mind bomb proteins in the antiviral arsenal.
AB  - In this issue of Immunity, Li et al. (2011) reported a dynamic protein
      interactome network underlying antiviral innate immune response and established
      the role of Mind Bomb proteins in the anti-RNA viral innate immune response.

PMID- 21943490
TI  - Case management of chiropractic patients with cervical brachialgia: A survey of
      French chiropractors.
AB  - BACKGROUND: Not much is known about the French chiropractic profession on, for
      example, level of consensus on clinical issues. OBJECTIVES: The first objective
      was to investigate if French chiropractors' management choices appeared
      reasonable for various neck problem scenarios. The second objective was to
      investigate if there was agreement between chiropractors on the patient
      management. The third objective was to see to which degree and at what stages
      chiropractors would consider to interact with other health-care practitioners,
      such as physiotherapists, general practitioners and specialists. METHOD: A
      questionnaire was sent to a randomly selected sample of all French chiropractors
      known to the national chiropractic college. It consisted of an invitation to
      participate in the study, a brief case description, and drawings of five stages
      of how a case of neck pain gradually evolves into a brachialgia to end up with a
      compromised spinal cord. Each stage offered five management choices. Participants
      were asked at what stages patients would be treated solely by the chiropractor
      and when patients would be referred out for second opinion or other care without
      chiropractic treatment, plus an open ended option, resulting in a "five-by-six"
      table. The percentages of respondents choosing the different management
      strategies were identified for the different scenarios and the 95% confidence
      intervals were calculated. There was a pre hoc agreement on when chiropractic
      care would or would not be suitable. Consensus was arbitrarily defined as
      "moderate" when 50- 69% of respondents agreed on the same management choice and
      as "excellent" when 70% or more provided the same answer. It was expected that
      inter professional contacts would be rare. RESULTS: The response rate was 53% out
      of 254 potential participants. The first two uncomplicated cases would generally
      have been treated by the chiropractors. As the patient worsened, the responses
      tended towards external assistance and for the most severe case, the majority of
      respondents would have referred the patient out. There was excellent consensus
      for the two extreme cases (the most benign and the most severe), moderate
      consensus for the cases next to these two and least agreement relating to the
      "middle" case. Inter-professional collaboration was contemplated mainly for the
      severe case. CONCLUSION: The French chiropractors who participated in this study
      seem to have a similar approach to patients with neck pain that gradually
      develops into a brachialgia and worsens. However, it is not known if the large
      group of non-participants in the study would agree with this treatment strategy.

PMID- 21943489
TI  - Chronic virus infection enforces demethylation of the locus that encodes PD-1 in
      antigen-specific CD8(+) T cells.
AB  - Functionally exhausted T cells have high expression of the PD-1 inhibitory
      receptor, and therapies that block PD-1 signaling show promise for resolving
      chronic viral infections and cancer. By using human and murine systems of acute
      and chronic viral infections, we analyzed epigenetic regulation of PD-1
      expression during CD8(+) T cell differentiation. During acute infection, naive to
      effector CD8(+) T cell differentiation was accompanied by a transient loss of DNA
      methylation of the Pdcd1 locus that was directly coupled to the duration and
      strength of T cell receptor signaling. Further differentiation into functional
      memory cells coincided with Pdcd1 remethylation, providing an adapted program for
      regulation of PD-1 expression. In contrast, the Pdcd1 regulatory region was
      completely demethylated in exhausted CD8(+) T cells and remained unmethylated
      even when virus titers decreased. This lack of DNA remethylation leaves the Pdcd1
      locus poised for rapid expression, potentially providing a signal for premature
      termination of antiviral functions.

PMID- 21943493
TI  - TiNS Special Issue: Hippocampus and Memory.

PMID- 21943488
TI  - Dendritic cell and macrophage heterogeneity in vivo.
AB  - Macrophage and dendritic cell (DC) are hematopoietic cells found in all tissues
      in the steady state that share the ability to sample the environment but have
      distinct function in tissue immunity. Controversies remain on the best way to
      distinguish macrophages from DCs in vivo. In this Perspective, we discuss how
      recent discoveries in the origin of the DC and macrophage lineage help establish
      key functional differences between tissue DC and macrophage subsets. We also
      emphasize the need to further understand the functional heterogeneity of the
      tissue DC and macrophage lineages to better comprehend the complex role of these
      cells in tissue homeostasis and immunity.

PMID- 21943491
TI  - Perceived parenting and risk for major depression in Chinese women.
AB  - BACKGROUND: In Western countries, a history of major depression (MD) is
      associated with reports of received parenting that is low in warmth and caring
      and high in control and authoritarianism. Does a similar pattern exist in women
      in China? METHOD: Received parenting was assessed by a shortened version of the
      Parental Bonding Instrument (PBI) in two groups of Han Chinese women: 1970
      clinically ascertained cases with recurrent MD and 2597 matched controls. MD was
      assessed at personal interview. RESULTS: Factor analysis of the PBI revealed
      three factors for both mothers and fathers: warmth, protectiveness, and
      authoritarianism. Lower warmth and protectiveness and higher authoritarianism
      from both mother and father were significantly associated with risk for recurrent
      MD. Parental warmth was positively correlated with parental protectiveness and
      negatively correlated with parental authoritarianism. When examined together,
      paternal warmth was more strongly associated with lowered risk for MD than
      maternal warmth. Furthermore, paternal protectiveness was negatively and maternal
      protectiveness positively associated with risk for MD. CONCLUSIONS: Although the
      structure of received parenting is very similar in China and Western countries,
      the association with MD is not. High parental protectiveness is generally
      pathogenic in Western countries but protective in China, especially when received
      from the father. Our results suggest that cultural factors impact on patterns of
      parenting and their association with MD.

PMID- 21943492
TI  - Pro-inflammatory cytokines and lipopolysaccharide induce changes in cell
      morphology, and upregulation of ERK1/2, iNOS and sPLA2-IIA expression in
      astrocytes and microglia.
AB  - BACKGROUND: Activation of glial cells, including astrocytes and microglia, has
      been implicated in the inflammatory responses underlying brain injury and
      neurodegenerative diseases including Alzheimer's and Parkinson's diseases.
      Although cultured astrocytes and microglia are capable of responding to pro
      inflammatory cytokines and lipopolysaccharide (LPS) in the induction and release
      of inflammatory factors, no detailed analysis has been carried out to compare the
      induction of iNOS and sPLA2-IIA. In this study, we investigated the effects of
      cytokines (TNF-alpha, IL-1beta, and IFN-gamma) and LPS + IFN-gamma to induce
      temporal changes in cell morphology and induction of p-ERK1/2, iNOS and sPLA2-IIA
      expression in immortalized rat (HAPI) and mouse (BV-2) microglial cells,
      immortalized rat astrocytes (DITNC), and primary microglia and astrocytes.
      METHODS/RESULTS: Cytokines (TNF-alpha, IL-1beta, and IFN-gamma) and LPS + IFN
      gamma induced a time-dependent increase in fine processes (filopodia) in
      microglial cells but not in astrocytes. Filopodia production was attributed to
      IFN-gamma and was dependent on ERK1/2 activation. Cytokines induced an early (15
      min) and a delayed phase (1 ~ 4 h) increase in p-ERK1/2 expression in microglial
      cells, and the delayed phase increase corresponded to the increase in filopodia
      production. In general, microglial cells are more active in responding to
      cytokines and LPS than astrocytes in the induction of NO. Although IFN-gamma and
      LPS could individually induce NO, additive production was observed when IFN-gamma
      was added together with LPS. On the other hand, while TNF-alpha, IL-1beta, and
      LPS could individually induce sPLA2-IIA mRNA and protein expression, this
      induction process does not require IFN-gamma. Interestingly, neither rat
      immortalized nor primary microglial cells were capable of responding to cytokines
      and LPS in the induction of sPLA2-IIA expression. CONCLUSION: These results
      demonstrated the utility of BV-2 and HAPI cells as models for investigation on
      cytokine and LPS induction of iNOS, and DITNC astrocytes for induction of sPLA2
      IIA. In addition, results further demonstrated that cytokine-induced sPLA2-IIA is
      attributed mainly to astrocytes and not microglial cells.

PMID- 21943494
TI  - [Jaw osteosarcomas].
AB  - INTRODUCTION: Osteosarcoma (OS) is the most frequent bone malignant tumor. It is
      usually found on long bones, 5 to 10% are located on jaws, accounting for 0.5 to
      1% of all facial tumors. There is little published data which concerns only few
      patients. Our aim was to study retrospectively cases of facial bone OS in adults,
      and to compare our results with published data to suggest an optimal management
      scheme. PATIENTS AND METHOD: Thirty-three patients were managed for an OS, from
      January 1997 to January 2007. Fourteen patients with a maxillary and mandibular
      OS, treated in first-intention in our unit, were included. The following data
      were analyzed: age; personal history; circumstance of discovery; clinical,
      functional, and physical signs; loco-regional extension and metastasis
      radiological investigation. The histological slides were systematically reviewed.
      The protocol, therapeutic outcome, and follow-up were studied. RESULTS: The mean
      age at diagnosis was 43. Swelling was the most frequent functional sign. The mean
      delay before management was 3.4 months. The most frequent radiological
      presentation was a lytic and hyperdense image. The diagnosis was suggested after
      CT scan in 57.1% of cases. The biopsy was correlated to the anatomopathological
      analysis in 78.6% of cases. The most common treatment was surgical exeresis
      completed by chemotherapy. The 5-year survival rate was 50%. DISCUSSION: Jaw OS
      are specific because of their localization and specific bone ultrastructure.
      Their management remains controversial: should they be managed like limb OS or
      treated more specifically? Neoadjuvant chemotherapy, even if it delays exeresis
      for 3 months, seems to stop the growth or reduce the tumor. An early
      anatomopathological analysis of the surgical piece determines adjuvant therapy.
      The negative prognostic factors are: maxillary localization because of limited
      exeresis margins, tumoral size, and osteoblastic sub-type.

PMID- 21943495
TI  - [Tongue reconstruction with a bilateral infrahyoid flap innervated by Ansa
      Cervicalis after total glossectomy].
AB  - INTRODUCTION: Reconstruction after total glossectomy remains a functional
      challenge. It must provide a large volume to ensure adequate phonation and
      swallowing. We present the larynx sparing bilateral infrahyoid flap
      reconstruction procedure after total glossectomy. PATIENTS AND METHOD: Three
      patients managed for an epidermoid carcinoma of the tongue, classified T4N0,
      underwent total glossectomy. The tongue was reconstructed with a bilateral
      infrahyoid flap pedicled on two superior thyroid arteries and innervated by Ansa
      Cervicalis. RESULTS: Oral food intake was resumed after 8 to 20 days. No false
      route was observed. The muscular flap mobility was clinically satisfactory. It
      was assessed by EMG in one case. Esophageal transit confirmed the absence of
      stasis and false route for one patient. DISCUSSION: This short series proves the
      feasibility of bilateral innervated and pedicled infrahyoid flap procedure. It is
      an alternative to volumetric and functional reconstruction after total
      glossectomy. The indications are rare and restricted to patients without IIa
      nodal region invasion. Our results are still limited and need to be confirmed by
      a larger series and by a more systematic assessment.

PMID- 21943496
TI  - [Para-pharyngeal tumors, contribution of imaging].
AB  - OBJECTIVES: Para-pharyngeal tumors are located deeply. Imaging is mandatory for
      their management. We conducted a retrospective study to determine the
      contribution of imaging for their diagnosis and treatment. PATIENTS AND METHODS:
      Imaging was performed for 20 cases of primary para-pharyngeal tumors between 1986
      and 2008. We compared the imaging to the anatomic and histological features of
      these tumors. RESULTS: Computed tomography and MRI confirmed the para-pharyngeal
      location of tumors. Tumors were located in the prestyloid compartment in eight
      cases, in the retrostyloid compartment in five cases, and in the retropharyngeal
      compartment in one case. Six tumors had filled all the para-pharyngeal space.
      Salivary gland tumors had filled the prestyloid space in two cases, and in two
      other malignant cases all para-pharyngeal space were invaded. MRI failed to
      differentiate the nature of tumor and its malignancy except when there was
      obvious bone erosion. The treatment was mainly surgical. The mean follow-up was 5
      years 6 months. DISCUSSION: Imaging contributes to the etiological diagnosis and
      assesses tumor extension, thus helping to choose the surgical approach. MRI is
      the most contributive examination; its resolution is more adapted to the
      diagnosis of deep tumors. CT scan is contributive when studying the bone
      structure.

PMID- 21943497
TI  - Child witch hunts in contemporary Ghana.
AB  - OBJECTIVE: The persecution of children as witches has received widespread
      reportage in the international mass media. In recent years, hundreds of children
      have been killed, maimed and abandoned across Africa based on individual and
      village-level accusations of witchcraft. Despite the media focus, to date, very
      little systematic study has investigated the phenomenon. In this case study, the
      persecution of child witches in Ghana is studied to explore the nature and
      patterns of witch hunts against children in the West African nation. METHODS:
      There are no reliable national data on child abuse related to witchcraft
      accusations in Ghana. For this study, 13 cases of child witch hunts appearing in
      the local media during 1994-2009 were analyzed. Case summaries were constructed
      for each incident to help identify the socio-demographic characteristics of
      assailants and victims, victim-offender relationships, the methods of attacks,
      the spatial characteristics, as well as the motivations for the attacks. RESULTS:
      Children branded as witches ranged in age from 1-month-old to 17-years-old, were
      primarily from poor backgrounds, and lived in rural areas of the country.
      Accusations of witchcraft and witch assaults were lodged by close family members
      often through the encouragement of, or in concert with Christian clergymen and
      fetish priests. Accused witches were physically brutalized, tortured, neglected,
      and in two cases, murdered. For school-aged children, imputations of witchcraft
      contributed to stigmatization in both the community and at school, resulting in
      dropping out. The most frequently expressed reason for persecution of the child
      was suspicion that the child had used witchcraft to cause the death or illness of
      family relations or someone in the community. Another reason was suspicion that
      the child was responsible for the business failure or financial difficulties of a
      perceived victim. CONCLUSIONS: The results of this research are consistent with
      findings in the witchcraft literature suggesting that seemingly inexplicable
      illnesses, untimely deaths, and financial hardships tend to be the major causal
      forces generating witch hunts. Additional research is necessary to further shed
      light on child witch hunts in Ghana and other countries. PRACTICE IMPLICATIONS:
      To reduce the incidence of such abuse, there is a need for increased advocacy and
      protections for children in the society. The government must also increase the
      penalties for child abuse. This will serve as a deterrent to potential offenders.
      Additionally, through public service campaigns, educating citizens about the
      causes and trajectories of diseases, will lead to a significant diminution of
      witchcraft accusations and the associated violence.

PMID- 21943498
TI  - Academic achievement despite child maltreatment: a longitudinal study.
AB  - PURPOSE: Although researchers have concluded that child maltreatment has a
      negative effect on children's learning and academic achievement, not all children
      are negatively affected by maltreatment, and some children seem to succeed
      academically despite being maltreated. Drawing on risk and resilience theory, we
      examined a broad range of potential risk, promotive, and protective factors
      within children and their environments along with characteristics of the
      maltreatment to account for variability in test scores. METHODS: A national
      longitudinal probability sample of 702 maltreated school-aged children, ages 6
      10, and their caregivers was used to predict reading and math scores among
      maltreated children over three years. RESULTS: We found that chronic
      maltreatment, poorer daily living skills, and lower intelligence explained a
      substantial proportion of the variance in maltreated children's math scores
      (39%), whereas type of maltreatment, poorer daily living skills and lower
      intelligence explained a substantial proportion of the variance in reading scores
      (54%) over time. Contrary to our prediction, having a behavior problem seemed to
      protect chronically maltreated children from poorer performance in math over
      time. CONCLUSIONS: To increase academic achievement among maltreated children, it
      is imperative that we prevent chronic maltreatment and help children increase
      their competency on daily living skills.

PMID- 21943499
TI  - Preparation, characterization and osteoblastic activity of
      chitosan/polycaprolactone/in situ hydroxyapatite scaffolds.
AB  - Calcium-deficient hydroxyapatite (cd-HA) crystals with a rod-like shape, 10-30 nm
      in diameter and 60150 nm in length, were prepared via a hydrothermal method in
      the presence of poly(acrylic acid) (PAA) (in situ HA). Scaffolds composed of
      chitosan (CS), polycaprolactone (PCL) and in situ HA were prepared by freeze
      drying, using a formic acid/acetone mixture as a shared solvent. The mass
      fraction of in situ HA in the scaffolds ranged from 0 to 40%. FT-IR and XRD
      studies indicated that hydrogen bonding interactions existed among CS, PCL and in
      situ HA, which suppressed the crystallization of PCL. The mechanical results
      demonstrated that the CS/PCL composites had the maximum flexural stress (308.14
      +/- 8.86 MPa), which was significantly higher than 2.92 +/- 0.02 MPa for the
      CS/in situ HA control. The effects of scaffolds on MC3T3-E1 cells were studied by
      measuring the viability, proliferation, adhesion, alkaline phosphatase activity,
      as well as mineralization assay. The WST-1 assay showed that in situ HA-loaded
      scaffolds had higher cell viability than CS/PCL scaffolds. SEM images of the cell
      seeded scaffolds revealed a significant promotion of cell adhesion in in situ HA
      loaded scaffolds. Moreover, ALP and mineralization were found to be enhanced in
      in situ HA-loaded scaffolds. All these results indicate that in situ HA-loaded
      scaffolds support cellular functions of osteoblastic cells and may serve as
      promising bone scaffolds. 

PMID- 21943501
TI  - Sticking a fork in cohesin--it's not done yet!
AB  - To identify the products of chromosome replication (termed sister chromatids)
      from S-phase through M-phase of the cell cycle, each sister pair becomes tethered
      together by specialized protein complexes termed cohesins. To participate in
      sister tethering reactions, chromatin-bound cohesins become modified by
      establishment factors that function during S-phase and bind to DNA replication
      fork components. Early models posited that establishment factors might move with
      replication forks, but that fork progression takes place independently of
      cohesion pathways. Recent studies now suggest that progression of the replication
      fork and/or S-phase are slowed in cohesion-deficient cells. These findings have
      led to speculations that cohesin ring-like structures normally hinder fork
      progression but coordinate origin firing during replication. Neither model,
      however, fully explains the diverse effects of cohesion mutation on replication
      kinetics. I discuss these challenges and then offer alternative views that
      include cohesin-independent mechanisms for replication-fork destabilization and
      transcription-based effects on S-phase progression.

PMID- 21943500
TI  - Erythropoietin in the intensive care unit: beyond treatment of anemia.
AB  - Erythropoietin (EPO) is the major hormone stimulating the production and
      differentiation of red blood cells. EPO is used widely for treating anemia of
      critical illness or anemia induced by chemotherapy. EPO at pharmacological doses
      is used in this setting to raise hemoglobin levels (by preventing the apoptosis
      of erythroid progenitor cells) and is designed to reduce patient exposure to
      allogenic blood through transfusions. Stroke, heart failure, and acute kidney
      injury are a frequently encountered clinical problem. Unfortunately, in the
      intensive care unit advances in supportive interventions have done little to
      reduce the high mortality associated with these conditions. Tissue protection
      with EPO at high, nonpharmacological doses after injury has been found in the
      brain, heart, and kidney of several animal models. It is now well known that EPO
      has anti-apoptotic effects in cells other than erythroid progenitor cells, which
      is considered to be independent of EPOs erythropoietic activities. This review
      article summarizes what is known in preclinical models of critical illness and
      discusses why this does not correlate with randomized, controlled clinical
      trials.

PMID- 21943502
TI  - Classes of conduct disorder symptoms and their life course correlates in a US
      national sample.
AB  - BACKGROUND: Population data on conduct disorder (CD) symptoms can help determine
      whether hypothesized subtypes of CD are sufficiently disparate in their familial,
      psychiatric and life course correlates to distinguish separate diagnostic
      entities. METHOD: Latent class analysis (LCA) of CD symptoms occurring before age
      15 was conducted in a national sample of adults aged 18-44 years from the
      National Epidemiological Study of Alcohol and Related Conditions. Associations of
      latent class membership with parental behavior problems, onset of psychiatric
      disorders and anti-social behaviors after age 15, adolescent life events (e.g.
      high school drop-out), and past-year life events (e.g. divorce/separation,
      bankruptcy) were estimated. RESULTS: LCA identified a no-CD class with low
      prevalence of all symptoms, three intermediate classes - deceit/theft, rule
      violations, aggression - and a severe class. The prevalence of CD, according to
      DSM-IV criteria, was 0% in the no-CD class, between 13.33% and 33.69% in the
      intermediate classes and 62.20% in the severe class. Latent class membership is
      associated with all the familial, psychiatric and life course outcomes examined.
      Among the intermediate classes, risk for subsequent mood/anxiety disorders and
      anti-social behavior was higher in the deceit/theft and aggressive classes than
      in the rule violations class. However, risk for adolescent life events is highest
      in the rule violations class. CONCLUSIONS: CD symptoms tend to occur in a
      partially ordered set of classes in the general population. Prognostically
      meaningful distinctions can be drawn between classes, but only at low levels of
      symptoms.

PMID- 21943503
TI  - The infusion of glucose in ewes during the luteal phase increases the number of
      follicles but reduces oestradiol production and some correlates of metabolic
      function in the large follicles.
AB  - Short-term nutritional supplementation stimulates folliculogenesis in ewes
      probably by insulin-mediated actions of glucose in the follicle. The aim of this
      study was to determine the effect of glucose on follicle number and granulosa
      levels of Aromatase P450 and phosphorylated Akt and AMPK. Twelve Ile-de-France
      ewes were allocated to two groups; one (n=7) infused with saline and the other
      (n=5) with glucose (10mM/h) for 72h in the luteal phase. At the end of infusion,
      ovaries were collected and all follicles >1mm in diameter were dissected to
      recover granulosa cells. Aromatase P450 and phosphorylated Akt and AMPK were
      analysed by Western blotting of granulosa cell lysates. Blood plasmas collected
      before and during the infusions were analysed for progesterone, oestradiol, LH,
      FSH, glucose, insulin and IGF-I. The infusion of glucose significantly increased
      follicle number but, significantly reduced Aromatase P450 and phosphorylated Akt
      and AMPK in granulosa cells. The circulating concentration of glucose rose
      significantly 3h after the start of the glucose infusion and remained elevated
      until 27h then fell; the circulating concentration of insulin rose significantly
      by 3h and remained elevated. The circulating concentration of oestradiol fell
      significantly by 32h and remained low; the circulating concentrations of LH and
      FSH were unaffected. These data show that short-term infusion of glucose
      stimulated follicular growth but decreased Aromatase P450 in granulosa cells. The
      reduced levels of phosphorylated Akt and AMPK suggest that the
      phosphatidylinositol 3-kinase pathway has been inhibited by high concentrations
      of glucose. These data also suggest that there may be functional cross-talk
      between FSH and insulin signalling in granulosa cells.

PMID- 21943504
TI  - Advances in transplantation.

PMID- 21943505
TI  - Bilateral leg symptoms--the T10 syndrome?
AB  - Prior studies have investigated the role of the sympathetic nervous system and
      the thoracic spine related to the upper extremities (known as the T4 syndrome).
      However, there is only little known about the role of the thoracic spine related
      to the lower extremities. In this case report, a patient with a heavy, tired
      feeling in both legs and hypomobile thoracic segments was treated with passive
      mobilisations of the thoracic spine.

PMID- 21943506
TI  - [Isolated congenital adenohypophyseal hypoplasia].

PMID- 21943507
TI  - [Profile of adolescents seen in emergency departments with acute alcohol
      poisoning].
AB  - INTRODUCTION: In recent years, the prevalence of Acute Alcohol Intoxication (AAI)
      in adolescents has increased. One of its impacts had been the increase in
      consultations in the Emergency Services (ES). The objective of this study is to
      assess the psychosocial profile of adolescents who consult for AAI and study
      their personal, family and social functioning. METHODS: 104 families of
      adolescents who attended for AAI in ES and 104 controls, matched by age and sex,
      were interviewed by telephone to obtain sociodemographic, clinical, academic and
      family functioning data. RESULTS: 72% of the adolescents who were attended for
      AAI were under 16 years old. Academic data showed that 37.7% had repeated a
      school year, 20% had truancy and 19.6% abandoned their basic studies. 9,8% were
      in psychiatric treatment. Only 11.4% of patients were referred to specialist
      service. There were no significant differences between in any of the clinical
      variables between the study and control group. CONCLUSIONS: This study provides
      new information on the characteristics of this population and provides guidance
      on the need to develop protocols for working in the ES that includes not only
      biochemical/ toxicological parameters but also includes the assessment of
      psychosocial parameters.

PMID- 21943508
TI  - Sex differences in effects of excitotoxic spinal injury on below-level pain
      sensitivity.
AB  - Effects of excitotoxic injury to the thoracic gray matter on sensitivity to below
      level nociceptive stimulation were evaluated for female and male Long-Evans rats.
      Operant escape and lick/guard (L/G) reflex responses to thermal stimulation were
      evaluated before and for 13-15 weeks after: 1) injections of quisqualic acid
      (QUIS) into the thoracic gray matter (T8-9), 2) laminectomy and spinal exposure
      and penetration without injection (sham) or 3) no surgical procedure (control).
      L/G responding to heat stimulation (44  degrees C) was unaffected for females and
      males following thoracic QUIS injections. Similarly, male escape performance was
      not significantly altered for 44  degrees C or 10  degrees C stimulation after
      QUIS injections or sham surgery. However, escape testing following QUIS and sham
      injections revealed increased heat sensitivity (44  degrees C) and decreased cold
      sensitivity (10  degrees C) for females. This selective effect is indicative of
      altered sympathetic activation by the thoracic injections. The effect of sham
      surgery suggests that female rats are vulnerable to ischemic injury during
      exposure and manipulation of the spinal cord. Escape from nociceptive heat and
      cold sensitivity of control males and females was unchanged over 13-15 weeks of
      testing.

PMID- 21943509
TI  - Photodegradation of hazardous dye quinoline yellow catalyzed by TiO2.
AB  - The photocatalytic degradation of hazardous dye quinoline yellow, employing a
      heterogeneous photocatalytic process using TiO(2) photocatalyst irradiated with 6
      W UV light source tungsten lamp, has been studied. The effect of various
      operational parameters, i.e., dye concentration, photocatalyst concentration, pH
      of the solution, substrate concentration, and electron acceptor such as hydrogen
      peroxide on the degradation rate of aqueous solutions of quinoline yellow has
      been examined. The disappearance of the dye follows a pseudo first order kinetics
      according to the Langmuir Hinshelwood model. Results show that the use of an
      efficient photocatalyst and the selection of optimal operational parameters may
      lead to complete decolorization and to sustainable decrease in the chemical
      oxygen demand (COD) of the dye waste water.

PMID- 21943510
TI  - Imaging of blood plasma coagulation at supported lipid membranes.
AB  - The blood coagulation system relies on lipid membrane constituents to act as
      regulators of the coagulation process upon vascular trauma, and in particular the
      2D configuration of the lipid membranes is known to efficiently catalyze
      enzymatic activity of blood coagulation factors. This work demonstrates a new
      application of a recently developed methodology to study blood coagulation at
      lipid membrane interfaces with the use of imaging technology. Lipid membranes
      with varied net charges were formed on silica supports by systematically using
      different combinations of lipids where neutral phosphocholine (PC) lipids were
      mixed with phospholipids having either positively charged ethylphosphocholine
      (EPC), or negatively charged phosphatidylserine (PS) headgroups. Coagulation
      imaging demonstrated that negatively charged SiO(2) and membrane surfaces
      exposing PS (obtained from liposomes containing 30% of PS) had coagulation times
      which were significantly shorter than those for plain PC membranes and EPC
      exposing membrane surfaces (obtained from liposomes containing 30% of EPC).
      Coagulation times decreased non-linearly with increasing negative surface charge
      for lipid membranes. A threshold value for shorter coagulation times was observed
      below a PS content of ~6%. We conclude that the lipid membranes on solid support
      studied with the imaging setup as presented in this study offers a flexible and
      non-expensive solution for coagulation studies at biological membranes. It will
      be interesting to extend the present study towards examining coagulation on more
      complex lipid-based model systems.

PMID- 21943511
TI  - Controlling the primary particle evolution process towards silica monoliths with
      tunable hierarchical structure.
AB  - In order to establish the hierarchical structure in multiple levels on mesoporous
      silica, this article reports a new strategy to prepare the monolith with the pore
      configuration in nanometer scale, micro-morphology in micrometer level and
      macroscopic shape in millimeter or larger grade. These hierarchical monoliths are
      synthesized in a weak acidic condition by using triblock copolymer P123, hydroxyl
      carboxylic acid and tetramethyl orthosilicate (TMOS), and the textural properties
      of the mesostructure can be facilely adjusted by simply controlling the synthesis
      condition without any additive. During the synthesis, the primary particles can
      be selectively synthesized as monodispersed sphere, noodle, prism, straight rods
      with different size or irregular bars, and their connection plus arrangement in
      3D directions can be also regulated. Therefore, various textural properties of
      mesopore are able to be altered including pore size (5.5-10.6 nm), total pore
      volume (0.48-1.2 cm(3) g(-1)), micropore surface area (47-334 m(2) g(-1)), and
      pore shape (from 2D or 3D straight channel to plugged channel). Moreover, these
      monoliths exhibit a considerable mechanical strength; they are also applied in
      eliminating particulate matters and tobacco special nitrosamines (TSNA) in
      tobacco smoke, exhibiting various morphology-assisted functions.

PMID- 21943512
TI  - Solvent colorimetric paper-based polydiacetylene sensors from diacetylene lipids.
AB  - A well known unique property of polydiacetylenes (PDAs) is the colorimetric
      response to external stimuli making it one of the most studied conjugated
      polymers for sensing applications. Here we report the synthesis of a novel series
      of diacetylene acids from the condensation of pentacosa-10,12-diynylamine
      (PCDAmine) and dicarboxylic acid or its anhydrides. One of these diacetylene
      lipids, 4-(pentacosa-10,12-diynylamino)-4-oxobutanoic acid (PCDAS), is used in
      combination with pentacosa-10,12-diynoic acid (PCDA) for dropcasting on pieces of
      filter paper which are consequently irradiated by UV light to generate a paper
      based sensor array for solvent detection and identification. Upon the exposure to
      various types of organic solvents, the blue colored sensors colorimetrically
      respond to give different shades of colors between blue to red. The color
      patterns of the sensor array are recorded as RedGreenBlue (RGB) values and
      statistically analyzed by principal component analysis (PCA). The PCA score plot
      reveals that the array is capable of identifying eleven common organic solvents.

PMID- 21943513
TI  - Adsorption of phenol from water by N-butylimidazolium functionalized strongly
      basic anion exchange resin.
AB  - N-butylimidazolium functionalized strongly basic anion exchange resin with Cl(-)
      anion (MCl) was prepared by anchoring N-butylimidazole onto chloromethylated
      macroporous styrene-divinylbenzene (St-DVB) copolymer. The adsorption
      performances of phenol on MCl were studied using the batch technique at acidic
      and alkaline pH. The studies showed that phenol can be effectively removed at
      both acidic and alkaline pH. The maximum adsorption was achieved at about pH 11.
      The maximum adsorption capacities of phenol on MCl at pH 6.6 and 11.2 were 80.2
      and 92.9 mg/g, respectively. The adsorption mechanism was mainly molecular
      adsorption at acidic pH and anion exchange at alkaline pH. The adsorption of
      phenol was hindered by the presence of Cl(-) and SO(4)(2-) at alkaline pH due to
      the competitive anion exchange reaction. The adsorption of molecular phenol
      species on MCl at acidic pH was exothermic, and the anion exchange of phenolate
      species by MCl at alkaline pH was endothermic. Desorption of phenol from loaded
      adsorbent was achieved by using 0.5 mol/L NaOH and 0.5 mol/L NaCl mixed solution.
      MCl can simultaneously remove phenol and Cr(VI) from their mixtures, which would
      be of practical value in actual industrial wastewater treatment.

PMID- 21943514
TI  - Novel, highly selective gold nanoparticle patterning on surfaces using pure
      water.
AB  - We present a simple, novel procedure to selectively deposit gold nanoparticles
      using pure water. It enables patterning of nanoparticle monolayers with a
      remarkably high degree of selectivity on flat as well as microstructured oxide
      surfaces. We demonstrate that water molecules form a thin "capping" layer on
      exposed thiol molecules within the mercaptan self-assembled layer. This
      reversible capping of water molecules locally "deactivates" the thiol groups,
      therewith inhibiting the binding of metallic gold nanoparticles to these specific
      areas. This amazing role of water molecules can be used as a tool to pattern flat
      as well as structured surfaces with gold nanoparticles.

PMID- 21943515
TI  - The explanatory gap is still there.
AB  - I argue that O'Regan & Noe's (O&N's) theory is in a no better position than any
      other theory to solve the "hard problem" of consciousness. Getting rid of the
      explanatory gap by exchanging sensorimotor contingencies for neural
      representations is an illusion.

PMID- 21943516
TI  - Evaluation of a wound dressing composed of hyaluronic acid and collagen sponge
      containing epidermal growth factor in diabetic mice.
AB  - This study investigated the effect of a wound dressing composed of hyaluronic
      acid (HA) and collagen (Col) sponge containing epidermal growth factor (EGF) on
      wound healing in diabetic mice. High-molecular-weight (HMW) HA aqueous solution,
      hydrolyzed low-molecular-weight (LMW) HA aqueous solution and heat-denatured Col
      aqueous solution were mixed, followed by freeze-drying to obtain a spongy sheet.
      Cross-linkage between Col molecules was induced by UV irradiation to the spongy
      sheet (Type-I wound dressing). In a similar manner, a spongy sheet containing EGF
      (Type-II wound dressing) was prepared by freeze-drying the mixed solution of HMW
      HA, LMW-HA and Col containing EGF. The efficacy of these products was evaluated
      in type-II diabetic BKS.Cg-+Lepr(db)/+Lepr(db) (db/db) mice. Wound dressings were
      applied to a full-thickness, dorsal skin defect measuring 1.5 cm * 2.0 cm,
      showing adipose tissue. In the control group, a commercially available artificial
      dermis composed of collagen spongy sheet (TERUDERMIS((r))) was used. A
      commercially available polyurethane film dressing (Bioclusive((r))) was applied
      over each wound dressing. After 1 week of application, wound conditions were
      evaluated based on their gross and histological appearances. Type-I and -II wound
      dressings promoted a decrease in wound size associated with angiogenesis and
      granulation tissue formation, compared with the artificial dermis. In particular,
      Type-II wound dressings promoted sufficient re-epithelialization. These findings
      indicate that the combination of HA, Col and EGF promotes wound healing by
      stimulating cell activity including cell migration and proliferation on the
      adipose tissue in a diabetic wound. Type-I and -II wound dressings would be
      useful to prepare a well-vascularized wound bed acceptable for split-thickness
      auto-skin grafting. 

PMID- 21943517
TI  - CDNF protects the nigrostriatal dopamine system and promotes recovery after MPTP
      treatment in mice.
AB  - Cerebral dopamine neurotrophic factor (CDNF) is a recently discovered protein,
      which belongs to the evolutionarily conserved CDNF/MANF family of neurotrophic
      factors. The degeneration of dopamine neurons following 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) treatment is well  characterized, and efficacy in this
      model is considered a standard criterion for development of parkinsonian
      therapies. MPTP is a neurotoxin, which produces parkinsonian symptoms in humans
      and in C57/Bl6 mice. To date, there are no reports about the effects of CDNF on
      dopamine neuron survival  or function in the MPTP rodent model, a critical gap.
      Therefore, we studied whether CDNF has neuroprotective and neurorestorative
      properties for the nigrostriatal dopamine system after MPTP injections in C57/Bl6
      mice. We found that bilateral striatal CDNF injections, given 20 h before MPTP, 
      improved horizontal and vertical motor behavior. CDNF pretreatment increased
      tyrosine hydroxylase (TH) immunoreactivity in the striatum and in the substantia
      nigra pars reticulata (SNpr), as well as the number of TH-positive cells in
      substantia nigra pars compacta (SNpc). Posttreatment with  CDNF, given 1 week
      after MPTP injections, increased horizontal and vertical motor behavior of mice,
      as well as dopamine fiber densities in the striatum and the number of TH-positive
      cells in SNpc. CDNF did not alter any of the analyzed dopaminergic biomarkers or
      locomotor behavior in MPTP-untreated  animals. We conclude that striatal CDNF
      administration is both neuroprotective and neurorestorative for the TH-positive
      cells in the nigrostriatal dopamine system in the MPTP model, which supports the
      development of CDNF-based treatment for Parkinson's disease.

PMID- 21943518
TI  - Performance comparison among multivariate and data mining approaches to model
      presence/absence of Austropotamobius pallipes complex in Piedmont (North Western
      Italy).
AB  - Freshwater inhabitants in Piedmont (Italy) have been deeply disadvantaged by
      environmental changes caused by human disturbance. Hence there are engendered
      species that need human intervention of an entirely different kind - better
      management through the development of innovative practical tools. The most
      ecologically important of the river-dwelling invertebrates is a threatened
      species, the native white-clawed crayfish Austropotamobius pallipes. This is the
      species that we focused on in our effort to contribute to species conservation.
      Specifically we contrasted three different techniques of managing data relating
      to the presence/absence of this species: logistic regression, decision-tree
      models and artificial neural networks (ANN). Logistic regression and decision
      tree models (unpruned and pruned) performed worse than ANN. In this case, tree
      pruning techniques did not make these models significantly more reliable, but did
      make the trees less complex and therefore did make the models clearer. ANN
      performed the best. Therefore we have judged them to be the most effective
      techniques.

PMID- 21943519
TI  - Analysis of genetic variability in Aristaeomorpha foliacea (crustacea,
      aristeidae) using DNA-ISSR (Inter Simple Sequence Repeats) markers.
AB  - This work reports the first genetic data of Aristaeomorpha foliacea, a marine
      decapod of high commercial value, from six Mediterranean localities and one new
      fishing ground in the Mozambique Channel. The use of five Inter Simple Sequence
      Repeat (ISSR) primers provided 150 polymorphic loci. Average estimates of genetic
      diversity did not significantly differ among sampled localities, with a mean
      value of heterozygosity H=0.105+/-0.015. Analysis of molecular variance (AMOVA)
      allocated>98% of genetic variability to the within-sample component, displaying
      values higher than those previously reported in ISSR studies on marine
      invertebrates. Cluster analyses did not detect geographically or genetically
      distinct groups. The observed lack of large-scale genetic differentiation is
      discussed in relation to the high potential for larval dispersal of the species
      and to features of the marker employed.

PMID- 21943521
TI  - Bone endocrine regulation of energy metabolism and male reproduction.
AB  - Usually vertebrate physiology is studied within the confined limits of a given
      organ, if not cell type. This approach has progressively changed with the
      emergence of mouse genetics that has rejuvenated the concept of a whole body
      study of physiology. A vivid example of how mouse genetics has profoundly
      affected our understanding of physiology is skeleton physiology. A genetic
      approach to bone physiology revealed that bone via osteocalcin, an osteoblast
      secreted molecule, is a true endocrine organ regulating energy metabolism and
      male reproduction. This ongoing body of work that takes bone out of its
      traditional roles is connecting it to a growing number of peripheral organs.
      These novel important hormonal connections between bone, energy metabolism and
      reproduction underscore the concept of functional dependence in physiology and
      the importance of genetic approaches to identify novel endocrine regulations.

PMID- 21943520
TI  - In nephrotic syndromes podocytes synthesize and excrete proteins into the tubular
      fluid: an electron and ion microscopic study.
AB  - Described here are the findings of an electron and ion microscopic study of renal
      biopsies of young children, with a particular attention to the intracytoplasmic
      and intranuclear changes observed in the podocytes of the proteinuric patients.
      In the cytoplasm, there is a considerable development of the ergastoplasm,
      associated with a dilatation of the endoplasmic reticulum and with the formation
      of large vacuoles containing nitrogen and sulfur. These changes are
      characteristics of cells synthesizing and excreting proteins. In the nuclei of
      many podocytes, the most striking change is a complete or quasi-complete
      disappearance of condensed chromatin, suggesting an intense transcription
      activity of the corresponding cells. The amount of the proteins excreted from the
      podocytes must be considered as significant, even if a quantitative evaluation
      was not possible.

PMID- 21943522
TI  - Comparative statistical mechanics of myosin molecular motors in rat heart,
      diaphragm and tracheal smooth muscle.
AB  - PURPOSE: Statistical mechanics establishes a link between microscopic properties
      of matter and its bulk properties. A. Huxley's equations (1957) [1] provide the
      necessary phenomenological formalism to use statistical mechanics. METHODS: We
      compared statistical mechanics in rat diaphragm in tetanus (tet; n=10) and twitch
      (tw; n=12) modes, in heart in twitch mode (n=20), and in tracheal smooth muscle
      in tetanus mode (TSM; n=10). This powerful tool makes it possible to determine:
      (i) statistical entropy (S) which is related to the dispersal of energy and
      represents a measure of the degree of disorder in muscular system; (ii)
      thermodynamic force A/T (chemical affinity A and temperature T); (iii)
      thermodynamic flow (upsilon); (iv) entropy production rate (A/T*upsilon), which
      quantifies irreversible chemical processes generated by myosin crossbridge (CB)
      molecular motors. RESULTS: All muscles studied operated near equilibrium, i.e.,
      A<<2500J/mol and in a stationary linear regime, i.e., A/T varied linearly with
      upsilon. The heart operated farther from equilibrium than both diaphragm (tet and
      tw) and TSM, as attested by its high entropy production rate. S was of the same
      order of magnitude in heart and TSM but lower in diaphragm (tet and tw).
      CONCLUSION: CB kinetics derived from A. Huxley's equations conferred a
      characteristic profile in terms of statistical mechanics on each muscle type. All
      studied muscles differed in terms of statistical entropy, chemical affinity, and
      entropy production rate. Stimulation mode (tet and tw) modulated CB kinetics and
      statistical mechanics. All muscle types operated near equilibrium and in a
      stationary linear regime.

PMID- 21943523
TI  - Blochmannia endosymbionts and their host, the ant Camponotus fellah: cuticular
      hydrocarbons and melanization.
AB  - Carpenter ants (genus Camponotus) have mutualistic, endosymbiotic bacteria of the
      genus Blochmannia whose main contribution to their hosts is alimentary. It was
      also recently demonstrated that they play a role in improving immune function as
      well. In this study, we show that treatment with an antibiotic produces a
      physiological response inducing an increase in both the quantity of cuticular
      hydrocarbons and in the melanization of the cuticle probably due to a nutritive
      and immunological deficit. We suggest that this is because it enhances the
      protection the cuticle provides from desiccation and also from invasions by
      pathogens and parasites. Nevertheless, the cuticular hydrocarbon profile is not
      modified by the antibiotic treatment, which indicates that nestmate recognition
      is not modified.

PMID- 21943524
TI  - Conservation of Mediterranean wetlands: interest of historical approach.
AB  - The wetlands of North Africa are an endangered and invaluable ecological
      heritage. Some of these wetlands are now protected by various conservation
      statutes; which actual impact has not yet been reliably evaluated. This article
      aims to assess the conservation management (Nature Reserve and Ramsar site) of a
      protected Tunisian lake, Majen Chitane, by using palaeoecological, historical and
      modern data, and by comparing it with the unprotected lake Majen Choucha. While
      located in similar environments, these lakes are today home to very different
      flora. Baseline conditions reconstructed from literature indicate that both lakes
      were very similar until the 1950s, and comparable to the current state of Majen
      Choucha, housing rich oligotrophic plant communities. In the 1960s, at the time
      that cultivation of the adjacent peatland began, Majen Chitane underwent strong
      ecological changes as the initial oligotrophic plant, diatom and zooplankton
      communities were replaced by eutrophication-tolerant ones. Eutrophication led to
      the local extinction of 40-55% of the hydrophytic and temporary-pool plant
      species, including those characteristic of the Isoetion. Given the damages and
      despite the recent conservation status of the site, it's unlikely that Majen
      Chitane will undergo any natural regeneration. Restoring it would start with
      completely protecting the complex lake-peatland and re-introducing the locally
      extinct species from Majen Choucha. This work exemplifies the usefulness of
      connecting palaeoecological, historical and modern data for the conservation of
      Mediterranean wetlands.

PMID- 21943525
TI  - [Threats to and conservation of North African wetlands: the case of the Ramsar
      site of Beni-Belaid (NE Algeria)].
AB  - Because of their biogeographical and geomorphological context, the northeastern
      Algeria wetlands present high species and community richness. The vegetation
      study of the Ramsar site of Beni-Belaid (Kabylia) showed the existence of four
      main communities, distributed along gradients of hydrology and disturbance. The
      obtained results reveal worrying threats on short term: overgrazing results in
      the lake invasion by the sand eroded from the coastal dune; agriculture induces
      illegal cutting, water pollution and excessive groundwater pumping; finally,
      hunting and fishing are illegally practiced into the Ramsar site. The awareness
      of public authorities is needed in order: (1) to completely protect the wetland
      with the aim of restoring a riparian forest belt; and (2) to initiate a campaign
      for increasing the local population awareness, and its involvement in
      conservation programs.

PMID- 21943526
TI  - Scorpions from the Island of Con Son (Poulo Condore), Vietnam and description of
      a new species of Chaerilus Simon, 1877 (Scorpiones, Chaerilidae).
AB  - The scorpion fauna of the Island of Con Son (Poulo Condore), Vietnam is briefly
      discussed and a new species, Chaerilus phami sp. n. is described. The new species
      is morphologically distinct from all the other species of Chaerilus described
      from the mainland in Vietnam.

PMID- 21943527
TI  - [Ambulatory oxygen: from scientific evidence to clinical practice].

PMID- 21943528
TI  - [Thoracic endometriosis and catamenial pneumothorax].

PMID- 21943529
TI  - [A fatal bong].

PMID- 21943530
TI  - [Primary ciliary dyskinesia: a retrospective review of clinical and paraclinical
      data].
AB  - INTRODUCTION: Primary ciliary dyskinesia (PCD) is an inherited disease
      responsible for a disruption of normal ciliary function. Its clinical
      presentation is usually in early childhood with pulmonary and
      otorhinolaryngologic symptoms. Early diagnosis is essential to avoid the
      development of bronchiectasis. The aim of the study was to retrospectively review
      the clinical features of children suspected to have PCD. RESULTS: A total of 89
      children had a bronchoscopy to perform a biopsy analyzed by transmission electron
      microscopy (TEM) in the childrens' hospital of Rennes between 2000 and 2009. PCD
      was diagnosed in 17 children, excluded in 51 and results were uncertain in 21
      children. Mean age at diagnosis was 6.5 years. In the PCD group, a history of
      neonatal respiratory distress was found in 40% of cases, 82% had had
      bronchopneumonia, 37% sinusitis, 82% recurrent otitis and 23% situs inversus.
      These subjects had defects in ciliary structure, 59% in the dynein arms, 35% in
      the central complex and 6% having both. Nasal nitric oxide production was
      consistent with the results of TEM in 16 cases: five PCD, 11 without PCD. In two
      cases, the results were discordant. CONCLUSION: This case series highlights the
      key clinical features of recurrent otitis, sinusitis, and situs inversus,
      especially when occurring in combination with bronchitic symptoms. Measures of
      nasal nitric oxide are useful for the diagnosis of PCD and in the case of high
      levels of NO, PCD is unlikely. Results may not be definitive and TEM analysis of
      biopsies is still indispensable to ensure the diagnosis and guide genetic
      counselling.

PMID- 21943531
TI  - [Costs of hospitalisation for exacerbations of COPD in patients receiving
      domiciliary rehabilitation].
AB  - INTRODUCTION: The aim of this study was to estimate the costs related to
      hospitalisation for exacerbations of COPD in patients who received domiciliary
      rehabilitation. METHODS: The hospital costs (obtained from the health insurance
      office of Bayonne) of 31 patients suffering from COPD of all stages, were
      analysed for the year of rehabilitation and for the preceding year. All the
      patients had access to the same management programme in a health care system:
      domiciliary bicycle ergometry, collective gymnastics, dietary advice,
      psychological support and education. RESULTS: The analysis of the costs of
      respiratory care revealed two populations: a minority in whom costs were
      increased (two end of life situations requiring palliative care and two severe
      episodes requiring intensive care), and a majority in whom domiciliary
      rehabilitation led to a reduction of over 60% in the costs related to
      hospitalisation. CONCLUSIONS: Respiratory rehabilitation reduces the costs of
      hospitalisation secondary to exacerbations in patients suffering from COPD but
      does not reduce the high costs related to severe episodes of respiratory failure
      or terminal care. It is important that rehabilitation is adapted to the needs of
      each patient until the end of his life.

PMID- 21943532
TI  - [Adherence to ambulatory oxygen therapy. Assessment and determinants in patients
      receiving long-term oxygen therapy].
AB  - BACKGROUND: The provision of ambulatory oxygen in addition to a stationary oxygen
      supply has been suggested to increase adherence to long-term oxygen therapy
      (LTOT) and promote ambulation. The degree of adherence to ambulatory oxygen
      therapy and the determinants of adherence remain largely unknown. METHODS: These
      were assessed in patients treated with LTOT (oxygen concentrator plus small
      oxygen cylinders with a demand oxygen delivery system [DODS]) in a tertiary care
      hospital supplied according to the Belgian criteria for LTOT refunding. Adherence
      to ambulatory oxygen was defined as mean use of ambulatory oxygen greater than 30
      min/day. Patients' files were reviewed and a questionnaire was sent for assessing
      patients' view on the use of ambulatory oxygen. RESULTS: Forty-six patients were
      included. Mean use of ambulatory oxygen was 40+/-36min/day. Twenty-three patients
      were adherent to ambulatory oxygen according to our definition. There was no
      difference between adherent and non-adherent patients regarding lung function or
      blood gases, nor was there any correlation between mean daily ambulatory oxygen
      use and any parameter. However, patients with MMRC 4 dyspnoea scale had a
      significantly lower use of ambulatory oxygen than patients with less severe
      dyspnoea (mean 33+/-24 vs 42+/-39min/day ; P=0.03) despite self reporting better
      adherence to LTOT. CONCLUSION: Adherence to ambulatory oxygen in this series of
      patients is quite low but at the higher end of data reported previously. Patients
      with MMRC 4 dyspnoea scale had a lower use of ambulatory oxygen despite reporting
      better adherence to LTOT. We could not identify any other predictive factors of
      adherence to ambulatory oxygen.

PMID- 21943533
TI  - [Pleural puncture biopsy in the aetiological diagnosis of pleurisy].
AB  - INTRODUCTION: Pleurisy represents a worrying situation because of the difficulty
      of aetiological diagnosis. The aim of this study was to evaluate the contribution
      of pleural puncture biopsy (PPB) in the diagnosis of pleurisy. METHODS: A
      prospective study of the contribution of the pleural puncture biopsy in the
      pulmonary service of Bamako (Mali) from 2005 to 2009. PPB was used in the
      investigation of exudative, non-purulent pleurisy of unknown aetiology. Castelin
      biopsy forceps were used. RESULTS: Pleurisy was the reason for 20% of the total
      admissions of 6374 patients. The PPB was performed in 390 patients or 30.6% of
      the cases of pleurisy. The HIV test was performed in 341 patients (87.4%), of
      whom 72 cases (21.1%) were positive. The pleural biopsies were: lymphocytic
      (68.7%), mixed cellular (17.1%). Histological interpretation was possible in 367
      biopsy specimens, a yield of 94.1%. Tuberculous granulomata were found in 65.1%
      with a close relationship to HIV status (P<0.004). Pleural cancer was found in
      16.1%. CONCLUSION: The PPB is easy to perform at a low cost. It permits the
      diagnosis of tuberculous and neoplastic pleurisy, particularly in low income
      countries with a high prevalence of TB/HIV.

PMID- 21943534
TI  - [Obstructive syndrome apnea. Practice study in general medicine].
AB  - INTRODUCTION: The obstructive sleep apnea syndrome (OSA) is a frequently
      occurring condition, which is becoming a major public health problem because it
      can be responsible for accidents due to excessive daytime drowsiness and because
      of associated cardiovascular complications. This study was aimed at testing the
      practice and knowledge of general practitioners relating to OSA. METHODS: Three
      hundred and thirty-four French military practitioners were surveyed using a
      questionnaire sent to them by post. Their results were analysed and compared to
      previously published data. RESULTS: Hundred and eight (32%) practitioners
      answered our questionnaire. About half of them (the younger practitioners) were
      comfortable with the management of this condition. Their knowledge about the risk
      factors and the symptoms of OSA was good but their knowledge about the physiology
      and the possible complications of OSA was insufficient. CONCLUSIONS: The results
      of this study are on the whole better than those previously published, and show
      that education has had some effect in this area. However, it remains the case
      that OSA is under diagnosed and a further intensification of efforts are needed
      to address this.

PMID- 21943535
TI  - [Predictive factors of lost to follow-up status during tuberculosis treatment].
AB  - INTRODUCTION: Patients with contagious tuberculosis who are lost to follow-up
      risk sowing the disease among their circle of acquaintances. Moreover, a history
      of inadequate anti-tuberculous treatment is an important risk factor for the
      development of drug-resistant organisms. The purpose of this study was to
      identify risk factors for loss to follow-up among patients undergoing treatment
      for tuberculosis. METHODOLOGY: We performed a prospective cohort study among
      patients with contagious tuberculosis, beginning with anti-tuberculous treatment
      followed during six months, after initial education-information about their
      condition. We compared the characteristics of 152 patients lost to follow-up from
      tuberculosis treatment against those of 492 patients who were not lost to follow
      up. RESULTS: Independent factors associated with a reduction in the risk of being
      lost to follow-up were: the presence of night-sweats (OR=0.46 [0.24-0.88];
      P=0.018), the presence of thoracic pain (OR=0.27 [0.14-0.54]; P<0.001), screening
      for HIV (OR=0.41 [0.17-0.98]; P=0.045), fact to inform a person of its disease
      (OR=0.06 [0.01-0.41]; P=0.004), the application of directly observed treatment in
      the community (OR=0.34 [0.17-0.66]; P<0.001). CONCLUSION: Reducing loss to follow
      up during treatment for tuberculosis requires the development of a "good
      attitude" through education-information about tuberculosis.

PMID- 21943536
TI  - [Indications for admitting patients with respiratory conditions in Sub-Saharan
      Africa].
AB  - INTRODUCTION: Respiratory diseases are the cause of a larger number of
      consultations than any other organ pathology; and general practitioners therefore
      spend considerable time treating them. The aim of this work was to investigate
      the indication for admission to hospital in patients with respiratory disease in
      a Sub-Saharan African context. PATIENTS: This was a retrospective observational
      study of the indications for admission to the pneumology department of the
      University Hospital of Point G. in Bamako, between January 2000 and December
      2009. Admission registers were used to verify data recorded in patients' medical
      records. RESULTS: Twelve thousand six hundred and forty records were collected;
      8621 men and 4019 women, mean age 49+/-13.5 years. 80.3% of admissions were for
      respiratory diseases and 19.7% for non-respiratory diseases largely
      cardiovascular and digestive conditions. The admission diagnosis and definitive
      diagnoses were dominated by tuberculosis, which made up 67% and 60% of cases
      respectively (P=0.000). The diagnosis was not specified in 2% of cases.
      CONCLUSION: The reason for admission to the respiratory service varied and
      included a proportion of non-respiratory diseases. We meet respiratory and non
      respiratory affections. Among pulmonary diseases, tuberculosis, bacterial
      pneumonia and pleurisy are the main reasons for admission.

PMID- 21943537
TI  - [Thoracic endometriosis: A difficult diagnosis].
AB  - Thoracic endometriosis is a rare disease, which presents in women at a mean age
      of 35 years, later than for pelvic endometriosis. There are no known predisposing
      factors for the condition and its pathogenesis is not yet clearly established.
      The symptoms always appear in connection with the periods of the person affected
      by the condition, occurring within 24-48 h after the start of menstruation.
      Catamenial pneumothorax is the most common clinical entity. It is associated with
      pelvic endometriosis in 30-50% of cases. Thoracoscopy, preferably performed
      during menstruation, allows full inspection of the diaphragm and the pleural
      cavity for defects in the diaphragm, endometrial nodules and bullae. The level of
      CA 125 is often elevated but this is not a reliable or specific marker. Medical
      treatment is aimed at blocking the action of estrogen on the endometrium and
      ectopic endometrial implants. GnRH analogues or danazol are the preferred
      treatments. Surgery to repair and strengthen the diaphragm and/or resect nodules
      or bullae also has a role, supplemented by pleurodesis to prevent further
      pneumothorax or effusions. The main risk is recurrence, and thus the current
      usual practice is to combine surgery, immediately followed by hormone therapy
      focusing on GnRH analogues.

PMID- 21943538
TI  - [Interstitial lung disease due to domestic moulds].
AB  - Identifying the role of fungi present in the domestic environment in the
      development of interstitial pneumonia can be a difficult clinical problem. We
      report a case of interstitial lung disease case occurring in a 53-year-old
      patient. He presented with profound hypoxemia (PaO(2) 54mmHg). Chest CT showed
      diffuse ground glass opacities. Initial blood tests for allergy and autoimmune
      disease were negative. Faced with a worsening of his clinical status after
      returning home he was hospitalized several times. At fibreoptic bronchoscopy,
      multiple white deposits were observed. Bronchoalveolar lavage with differential
      cell count was performed, revealing a 23% lymphocytosis. Serology for specific
      household molds showed moderate reaction to various molds found in homes,
      especially Stachybotrys chartarum. Pulmonary function tests revealed a moderate
      restrictive pattern with impaired diffusion of carbon monoxide and a
      bronchiolocentric interstitial pneumonia was found at lung biopsy. After a
      permanent move to a new residence, clinical parameters, radiological, biological
      and functional normalized. The final diagnosis was interstitial lung disease
      related to mycotoxins of S. Chartarum. The diagnosis of hypersensitivity
      pneumonitis to domestic mold or interstitial lung disease secondary to mycotoxins
      should be considered in patients presenting with interstitial pneumonia and
      requires specific investigations to ensure that an environmental cause with an
      allergic or toxic role is not missed.

PMID- 21943539
TI  - [Fatal alveolar haemorrhage following a "bang" of cannabis].
AB  - The new methods of cannabis consumption (home made water pipe or "bang") may be
      responsible for fatal respiratory complications. We present a case, with fatal
      outcome, of a man of 19 years with no previous history other than an addiction to
      cannabis using "bang". He was admitted to intensive care with acute dyspnoea. A
      CT scan showed bilateral, diffuse alveolar shadowing. He was anaemic with an Hb
      of 9.3g/l. Bronchoalveolar lavage revealed massive alveolar haemorrhage.
      Investigations for infection and immunological disorder were negative and
      toxicology was negative except for cannabis. Antibiotic treatment was given and
      favourable progress allowed early discharge. Death occurred 15 days later due to
      alveolar haemorrhage following a further "bang" of cannabis. Autopsy showed toxic
      alveolar haemorrhage. The probable mechanism is pulmonary damage due to acid
      anhydrides released by the incomplete combustion of cannabis in contact with
      plastic. These acids have a double effect on the lungs: a direct toxicity with
      severe inflammation of the mucosa leading to alveolar haemorrhage and
      subsequently the acid anhydrides may lead to the syndrome of intra-alveolar
      haemorrhage and anaemia described in occupational lung diseases by Herbert in
      Oxford in 1979. It manifests itself by haemoptysis and intravascular haemolysis.
      We draw attention to the extremely serious potential consequences of new methods
      of using cannabis, particularly the use of "bang" in homemade plastic materials.

PMID- 21943540
TI  - [Erasmus' syndrome with pseudo-tumour masses].
AB  - INTRODUCTION: Erasmus' syndrome involves the association of systemic scleroderma
      (SS) and exposure to silica. Silicosis may precede the SS but the latter may be
      the presentation, in which case a history of exposure to silica should be sought
      as part of the diagnosis. CASE REPORT: A 46-year-old man with history of
      pulmonary tuberculosis presented with dyspnoea and dysphagea. Clinical
      examination revealed thickening of the facial skin with a pointed nose, erythema
      and telangiectasia, Raynaud's syndrome and sclerodactyly. A thoracic CT scan
      revealed bilateral, fibrotic, pseudo-tumoural masses. Antinuclear antibodies,
      anti-topoisomerase 1 and antihistone were positive. CONCLUSION: The clinical
      presentation of Erasmus' syndrome associating systemic scleroderma and pulmonary
      pseudo-tumours may pose a problem of differential diagnosis from lung cancer.
      This condition requires regular clinical and radiological monitoring,
      particularly as both scleroderma and silicosis increase the risk of lung cancer.

PMID- 21943541
TI  - [Pulmonary Langerhans histiocytosis and Hodgkin's lymphoma].
AB  - Pulmonary Langerhans histiocytosis (PLH) is a rare disease due to the
      accumulation of Langerhans cells at the level of the bronchioles. These dendritic
      immunocytes form granulomata and destroy the wall of the airway. We report a case
      of PLH developing at the same time as Hodgkin's lymphoma in a young woman who
      smoked tobacco and cannabis. We observed a complete remission of the PLH lesions
      parallel to the remission of the Hodgkin's lymphoma after chemotherapy, in the
      absence of any change in the consumption of tobacco and cannabis. This
      observation leads us to discuss the potential relationships between PLH on one
      hand, and smoking, the lymphoma and its treatment on the other.

PMID- 21943542
TI  - [Superior vena cava obstruction without symptoms?].

PMID- 21943543
TI  - [Pulmonary nodules upon return from Costa Rica].

PMID- 21943544
TI  - [Recommendations for the prevention and management of occupational allergic
      rhinitis. Societe franc aise de medecine du travail. Societe de pneumologie de
      langue franc aise. Societe franc aise d'allergologie. Societe franc aise d'oto
      rhino-laryngologie et de chirurgie de la face et du cou].

PMID- 21943545
TI  - Five-year survival for lung cancer patients managed in general hospitals.
AB  - INTRODUCTION: In 2000, the college of pulmonologists of general hospitals
      undertook an epidemiological study (KBP-2000-CPHG) enrolling all new cases of
      histologically confirmed lung cancer managed in general hospitals. This paper
      reports the 5-year survival in these cases. METHODS: Vital status was available
      for 5447 out of 5667 patients included in the original study. The effect of
      different prognostic factors on mortality was assessed. RESULTS: At 5 years, 567
      patients (10.4%) were still alive. Median survival for the 4880 (89.6%) deceased
      patients was 7 months. Univariate analysis identified age, smoking history,
      performance status, histological type and disease stage (TMN classification) as
      determinants of survival. For non-small cell lung cancer (n=4885) multivariate
      analysis identified five predictive factors for mortality - age, gender,
      histological type, performance status and stage. CONCLUSIONS: Five-year survival
      in lung cancer continues to be poor. As the risk factors for poor outcome at the
      time of diagnosis are not modifiable and pending, the results of screening
      studies reduction in mortality must rest on primary prevention.

PMID- 21943546
TI  - Spirometric profile of narghile smokers.
AB  - INTRODUCTION: Studies of the spirometric profiles of narghile smokers are few,
      have some methodological limits (i.e. small sample size), and present
      contradictory conclusions. AIMS: (i) To determine the percentage of narghile
      smokers with obstructive ventilatory defect (OVD) and/or restrictive ventilatory
      defect (RVD) or static hyperinflation (SHI); (ii) to compare the chronological
      and estimated lung ages. POPULATION AND METHODS:  INCLUSION CRITERIA: men aged 20
      to 60 years, narghile smokers (>1 narghile-year [NY]). EXCLUSION CRITERIA: cigar
      or cigarette smokers and comorbidity. Narghile use quantification: NY and kg of
      cumulative tobacco use (1 NY=9.125 kg of cumulative tobacco use). DEFINITIONS:
      Large airway obstructive ventilatory defect (OVD): forced expired volume in one
      second (FEV(1))/forced vital capacity (FVC) less than lower limit of normal
      (LLN). Small airway OVD: FVC more than LLN and decrease (less than LLN) of one or
      more peripheral flows. RVD: total lung capacity (TLC) less than LLN. SHI:
      residual volume (RV) more than upper limit of normal. SPIROMETRIC MEASURES: (Vmax
      22 Series/6200 Autobox, SensorMedics, Yorba Linda, California, USA with
      measurement of functional residual capacity by nitrogen washout). Measurements
      were made according to international recommendations. RESULTS: One hundred and
      ten narghile smokers were included (34+/-10 years; 1.76+/-0.07m; 84+/-14kg).
      Thirty-six percent of the subjects had SHI; 14% had small airway OVD; 14% had
      RVD, and 6% had large airway OVD. Estimated lung age was higher than
      chronological lung age (47+/-18 years vs. 34+/-10 years, P<0.05). CONCLUSION:
      Narghile use accelerates lung ageing. This study provides the health authorities
      with valid arguments to fight this blight on society, which increasingly involves
      children and pregnant women.

PMID- 21943547
TI  - Home-based pulmonary rehabilitation in idiopathic pulmonary fibrosis.
AB  - INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a severe chronic lung
      disease. Pulmonary rehabilitation could improve the quality of life of patients
      with this condition. METHODS: We prospectively evaluated the impact of an 8-week
      home-based pulmonary rehabilitation programme over 10 months in stable patients
      suffering from IPF. Exercise capacity, pulmonary function, dyspnoea and quality
      of life were analyzed before and after the rehabilitation programme. RESULTS:
      Seventeen patients were included and 13 completed the study. Mean functional
      vital capacity (FVC) was 2.15+/-0.79L and mean diffusing capacity for carbon
      monoxide (DLCO) was 7.81+/-3.99mL/min/mmHg. Six patients were treated with low
      dose oral steroids (20mg/day of prednisone) with or without immunosuppressive
      treatments; six were taking part in therapeutic trials. Mean endurance time
      (7.4+/-9.1 min vs. 14.1+/-12.1 min; P=0.01), number of steps per minute on a
      stepper (322+/-97 vs. 456+/-163; P=0.026), six-minute walk distance relative to
      heart rate (HR) (11+/-6 vs. 17+/-12; P=0.006), exercise dyspnoea (P=0.026),
      sensation of physical limitation on the SF-36 (25%+/-26 vs. 49%+/-38; P=0.047)
      and four out of seven visual analogue scales were significantly improved after
      rehabilitation. In contrast, no significant difference was observed in resting
      pulmonary function or in other items on quality of life questionnaires.
      CONCLUSION: A home-based programme of pulmonary rehabilitation is feasible in IPF
      patients. It significantly improved endurance parameters and physical limitation
      in this patient group without changing pulmonary function.

PMID- 21943549
TI  - Complexation of amidated pectin with poly(itaconic acid) as a polycarboxylic
      polymer model compound.
AB  - Complexes based on amidated pectin (AP) and poly(itaconic acid) (PIA) were
      prepared by casting films from solutions of AP and PIA in different ratios with
      the pectin amount ranging from 10% to 90% by mass. The complexes were
      investigated by elemental analysis, Fourier-transform infrared spectroscopy
      (FTIR), scanning electron microscopy (SEM), and thermogravimetry (TG). In all
      investigated ratios of AP/PIA glassy transparent films with a uniform structure
      were obtained. The results of elemental analysis confirmed the composition of the
      complexes, and FTIR spectroscopy has shown carboxylic and amide peak shifting,
      indicating complex formation between AP and PIA. Comparison of thermograms of
      AP/PIA films with different ratios of AP indicated that the increase of the
      amount of AP increases the thermal stability of the films by retarding the onset
      of the main degradation processes.

PMID- 21943548
TI  - High prevalence of COPD symptoms in the general population contrasting with low
      awareness of the disease.
AB  - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is underdiagnosed
      because of limited disease awareness with trivialization of the symptoms in the
      general population. METHODS: A survey was conducted in a representative sample
      (n=2758) of individuals older than 40 years of age in the general population of
      France. Respiratory symptoms and knowledge about COPD were assessed in
      individuals with or at risk for COPD (n=860, 31% of the sample). RESULTS: In the
      overall sample, 40% of individuals had a Medical Research Council dyspnea grade
      of 1 or more but only 9% spontaneously reported shortness of breath. Of these 9%,
      72% reported limitations to their daily activities but only 14% believed they had
      severe lung disease. In the overall sample, only 220 (8%) individuals knew the
      term COPD and only 66% associated the term COPD with respiratory disease.
      CONCLUSIONS: Despite a large proportion of individuals at risk for COPD or having
      COPD and a high prevalence of breathlessness, awareness of respiratory symptoms
      and knowledge of COPD were limited. These findings indicate a need for educating
      the general population about COPD.

PMID- 21943550
TI  - Concise synthesis and antitumor activities of trisaccharide steroidal saponins.
AB  - The naturally derived trisaccharide steroidal saponin 1 and structurally modified
      derivatives 2 and 3 bearing the same sarsasapogenin aglycon were synthesized
      concisely via a direct transglycosylation strategy. The antitumor activities of
      the synthetic trisaccharide saponins 1-3 and their corresponding alpha-isomers 1a
      3a were preliminarily evaluated against human gastric adenocarcinoma cell (MKN
      45) and human epithelial cervical cancer cell (HeLa) by CCK-8 assay.

PMID- 21943551
TI  - Pathways of cadmium fluxes in the root of the halophyte Suaeda salsa.
AB  - Halophyte plants offer a greater potential for phytoremediation research for
      reducing the levels of toxic metals from saline soils than salt sensitive plants.
      Using the scanning ion-selective electrode technique, we analyzed the pattern and
      rate of Cd(2+) fluxes at different regions of the root apex of Suaeda salsa. The
      Cd(2+) influx in the rhizosphere was greatest near the root tip (within 150MUm of
      the tip). The results indicated that Cd(2+) influx into roots was significantly
      suppressed by the pre-treatment or in the presence of two kinds of Ca(2+) channel
      blockers; LaCl(3) and verapamil. The Cd(2+) influx was also reduced by N
      ethylmaleimide, a thiol blocker. Cd content determination and labeling of Cd
      using fluorescent dye support our conclusion. The results of this study provide a
      more stable theoretical basis for the phytoremediation of Cd contamination in
      saline soils of coastal zones.

PMID- 21943552
TI  - Cross-domain probabilistic inference in a clinical decision support system:
      examples for dermatology and rheumatology.
AB  - INTRODUCTION: Maintaining a large diagnostic knowledge base (KB) is a demanding
      task for any person or organization. Future clinical decision support system
      (CDSS) may rely on multiple, smaller and more focused KBs developed and
      maintained at different locations that work together seamlessly. A cross-domain
      inference tool has great clinical import and utility. METHODS: We developed a
      modified multi-membership Bayes formulation to facilitate the cross-domain
      probabilistic inferencing among KBs with overlapping diseases. Two KBs developed
      for evaluation were non-infectious generalized blistering diseases (GBD) and
      autoimmune diseases (AID). After the KBs were finalized, they were evaluated
      separately for validity. RESULT: Ten cases from medical journal case reports were
      used to evaluate this "cross-domain" inference across the two KBs. The resultant
      non-error rate (NER) was 90%, and the average of probabilities assigned to the
      correct diagnosis (AVP) was 64.8% for cross-domain consultations. CONCLUSION: A
      novel formulation is now available to deal with problems occurring in a clinical
      diagnostic decision support system with multi-domain KBs. The utilization of this
      formulation will help in the development of more integrated KBs with greater
      focused knowledge domains.

PMID- 21943553
TI  - Monitoring chronic patients between primary care and cardiology.

PMID- 21943554
TI  - [Three-dimensional imaging in cardiac resynchronization therapy].
AB  - Cardiac resynchronization therapy improves clinical symptoms and prognosis of
      heart failure patients. However, it has been shown that up to 40% of patients do
      not respond to this therapy. Three main determinants of cardiac resynchronization
      therapy response have been identified: left ventricular dyssynchrony, left
      ventricular lead position, and extent and location of myocardial scar tissue. Two
      dimensional echocardiography is the first imaging technique to evaluate patients
      who may be candidates for cardiac resynchronization therapy. However, a
      multimodality approach based on 3-dimensional imaging techniques may provide a
      more comprehensive evaluation of these patients by combining the assessment of
      the aforementioned pathophysiological determinants of cardiac resynchronization
      therapy response.

PMID- 21943555
TI  - Mentalizing impairment in schizophrenia: a functional MRI study.
AB  - BACKGROUND: A deficit in Theory of mind (ToM) or 'mentalizing' has been purported
      to underlie the poor social functioning seen in patients with schizophrenia. To
      understand the neural basis of this deficit studies have primarily used tasks
      requiring 'off-line' or explicit mentalizing but, in daily life, successful
      social interactions depend upon implicit or 'on-line' mentalizing. Therefore in
      the present study we used functional neuroimaging and a task that elicits 'on
      line' mentalizing to investigate the neural basis of ToM deficits in
      schizophrenia. METHODS: Functional MRI images were acquired from 20 male patients
      with established schizophrenia and 19 age and gender matched healthy controls
      while they watched animated sequences involving two triangles. In the control
      condition the two triangles moved at random whereas in the experimental condition
      they moved interactively with implied intentions. The identification of ToM
      networks and differential responses between groups, within this network, was
      investigated using a random effects model. To account for differences in
      educational status between the groups this was included as a covariate in the
      between group analysis. Correlation analysis was performed to examine the
      relationship between neural activity change during mentalizing and the clinical
      and functional outcomes of patients. RESULTS: Patients with schizophrenia had
      significantly diminished activity in the right superior temporal gyrus (STG) at
      the temporoparietal junction (TPJ) and bilaterally within the inferior frontal
      gyri (IFG). Interestingly, frontal neural activity showed significant correlation
      with functional outcomes in patients with schizophrenia. CONCLUSIONS: Findings
      from this novel study suggest that the ToM deficit in male schizophrenia patients
      may reflect impairment in the automatic or implicit processing of mentalizing. If
      replicated, this is an important finding that provides additional insight into
      the neural basis of impairments in social functioning that are experienced by
      patients with schizophrenia.

PMID- 21943556
TI  - Gray matters!--mapping the transition to psychosis.
AB  - Despite many neuroimaging studies on schizophrenia showing brain abnormalities
      the exact time course of their occurrence is unknown. Studies of gray matter are
      a powerful tool in biological psychiatry and provide an unprecedented opportunity
      for brain structure investigations. Here we compared cross-sectional and
      longitudinal structural neuroimaging studies distinguishing high-risk subjects
      developing psychosis from those who did not. These investigations on gray matter
      volumes in the prodromal phase potentially identify core structural markers of
      impending psychoses and clarify dynamic changes underlying the transition.
      Subjects at high risk of psychosis show qualitatively similar albeit less severe
      gray matter abnormalities as patients with psychosis.

PMID- 21943558
TI  - Primary hyperparathyroidism: Skeletal and non-skeletal effects, diagnosis and
      management.
AB  - Primary hyperparathyroidism (PHPT) is the third most common endocrinopathy seen
      today, and is most frequently found in the 6th to 7th decade of life. PHPT can
      present with various degrees of symptoms, and can affect many organ systems,
      including the skeletal, renal, central nervous system and cardiovascular system.
      Despite this, the most common presentation of hyperparathyroidism is
      "asymptomatic" with the diagnosis being made incidentally with the initial
      finding of hypercalcemia on routine laboratory studies, leading to further
      investigation. Surgical versus medical management is usually based on factors
      such as age and complications related to hyperparathyroidism (i.e. the presence
      of renal stones, renal insufficiency and bone loss and significant increases in
      serum calcium). Treatment options include parathyroidectomy, bisphosphonates,
      calcitonin and calcimimetics. In this review, we discuss primary
      hyperparathyroidism in detail with a focus on clinical manifestations
      particularly in the elderly population. We highlight the indications for surgical
      versus medical management and compare some of the uses of newer therapeutic
      agents relative to traditional ones.

PMID- 21943557
TI  - Sexual satisfaction in the elderly female population: A special focus on women
      with gynecologic pathology.
AB  - SEXUAL FUNCTION IN AGING WOMEN: Sexuality is an integral part of human
      expressions. Mental health plays a major role in sexuality. Several psychological
      interventions are proposed to increase the sexual quality of life in older women
      with diverse gynecologic pathology. A biopsychosocial approach utilizing brief
      strategies can be easily implemented in clinics to help women of all ages
      increase their sexual quality of life. THE IMPACT OF FEMALE PELVIC FLOOR
      DISORDERS ON SEXUAL FUNCTION IN OLDER WOMEN: Female pelvic floor disorders
      include urinary incontinence, pelvic organ prolapse, and fecal incontinence.
      These disorders increase dramatically with increasing age. Urinary incontinence
      has been demonstrated to have a negative impact on a woman's sexual function.
      Among sexually active older women with urinary incontinence, 22% report being
      moderately or extremely worried that sexual activity would cause urine loss. An
      increased prevalence of sexual distress [9% (6/76) vs. 1.3% (2/216), p=0.005] has
      been reported in sexually active women over 40 years old with urinary
      incontinence. Treatment of urinary incontinence can improve sexual function in
      older women. Among sexually active women (N=53) who underwent midurethral slings
      procedures for the correction of urinary incontinence, increased coital
      frequency, decrease fear of incontinence with coitus, decreased embarrassment due
      to incontinence was reported six months after surgery. Pelvic organ prolapse, a
      hernia of the vagina resulting in a visible vaginal bulge, has also been
      associated with a negative impact on sexual function. Women with advanced pelvic
      organ prolapse (POP-Q stage III or IV) have been demonstrated to have decreased
      body image reporting that they are more self-conscious about their appearance
      [adjusted odds ratio (AOR) 4.7; 95% confidence interval (CI) 2.9, 51], feel less
      feminine (AOR 4.0; 95% CI 1.2, 15) and less sexually attractive (AOR 4.6; 95% CI
      1.4, 17) compared with women who have normal pelvic support. Both vaginal and
      abdominal approaches to surgical correction of pelvic organ prolapse have been
      demonstrated to improve sexual function. MENTAL HEALTH: Mental health plays a
      major role in older woman's sexuality. Sexual interest and satisfaction is tied
      to emotional expressivity, women's self-worth, feelings of depression and
      loneliness as well as cognitive function. Research has shown that both general
      practitioners and specialists lack training in sexual assessments. Behavioral
      health specialists, such as a psychologist, can play an integral role in helping
      to facilitate communication between the patient and the provider. A main focus of
      communication training is to facilitate open and genuine conversation between the
      provider and the patient. Providers are encouraged to ask open ended questions
      while patients are encouraged to discuss symptoms while coping with an internal
      state of anxiety. Despite the known prevalence of sexual dysfunction among older
      women, few studied empirically based interventions have been published with these
      women. This speaks to the general assumption among medical professionals that
      having the "sex talk" in older women with gynecological pathology is not
      important or relevant. A biopsychosocial approach utilizing some of the
      aforementioned brief strategies can be easily implemented in comprehensive
      gynecology clinics in order to help women of all ages increase their sexual
      quality of life.

PMID- 21943559
TI  - The diagnostic value of intraocular fluid analysis by polymerase chain reaction
      in Thai patients with uveitis.
AB  - Uveitis is a major cause of severe visual impairment throughout the world and can
      be initiated by various infectious and non-infectious causes. Early recognition
      of specific infections is important as the treatment with antimicrobial agents
      might stop the progression or even cure the eye disease. To determine the
      infectious causes of uveitis in Thailand, intraocular fluid samples of 100 HIV
      negative patients and 47 HIV-positive patients with uveitis were examined using
      real-time PCR analysis for herpes simplex virus, varicella zoster virus,
      cytomegalovirus and Toxoplasma gondii. Positive PCR results were found in 33/100
      (33%) HIV-negative patients and in 33/47 (70%) HIV-positive patients with
      uveitis. In Thailand, cytomegalovirus was identified as the most frequent cause
      of infectious uveitis in both HIV-negative and HIV-positive patients (49 and 91%,
      respectively). PCR analysis of intraocular samples in uveitis was a valuable
      diagnostic assay. The pattern of uveitis observed in the Far East differs from
      that found in the West.

PMID- 21943560
TI  - Rational action selection in 11/2- to 3-year-olds following an extended training
      experience.
AB  - Previous studies failed to find evidence for rational action selection in
      children under 2 years of age. The current study investigated whether younger
      children required more training to encode the relevant causal relationships.
      Children between 11/2 and 3 years of age were trained over two sessions to
      perform actions on a touch-sensitive screen to obtain video clips as outcomes.
      Subsequently, a visual habituation procedure was employed to devalue one of the
      training outcomes. As in previous studies, 2- and 3-year-olds chose actions
      associated with an expected valued outcome significantly more often during a
      subsequent choice test. Moreover, analysis of children's first responses in the
      post-devaluation test revealed evidence of rational action selection even in the
      youngest age group (18-23 months). Consistent with dual-process accounts of
      action control, the findings support the view that the ability to make rational
      action choices develops gradually.

PMID- 21943561
TI  - Pediatric acne management: optimizing outcomes. Introduction.

PMID- 21943562
TI  - The effects of culture, skin color, and other nonclinical issues on acne
      treatment.
AB  - The effective and safe treatment of acne vulgaris often is affected by individual
      patient characteristics, including skin color and cultural background. Skin of
      color is especially prone to hyperpigmentation, both from lesions and from
      irritating therapy. Clinicians also should be aware of cultural attitudes and
      folk remedies that may adversely affect dermatologic conditions such as acne.

PMID- 21943563
TI  - Approach to pediatric acne treatment: an update.
AB  - By late adolescence, almost all individuals have experienced some degree of acne.
      A broad range of acne treatments has been shown to be safe and effective in
      adults. While still sparse, emerging data now also document similar safety and
      efficacy of these agents for children >12 years of age. For younger children with
      preadolescent acne, where data are more limited or unavailable, it seems
      reasonable to extrapolate from the findings of studies involving older children
      >12 years of age. This article reviews the latest evidence and current expert
      opinions on acne therapies in the pediatric age group.

PMID- 21943564
TI  - Acne life cycle: the spectrum of pediatric disease.
AB  - Acne is no longer simply a diagnosis based on the appearance of characteristic
      lesions on the skin of adolescents. The presentation of acne differs across age
      groups, and the population of younger pediatric patients with acne continues to
      grow. This article addresses the changing epidemiology and demographics of acne,
      with specific emphasis on the 7- to 11-year-old acne patient population; the
      differences and similarities between pediatric acne and adolescent acne; age
      based acne epidemiology; and current perspectives on acne etiology.

PMID- 21943565
TI  - Parents as partners in pediatric acne management.

PMID- 21943566
TI  - The acne continuum: an age-based approach to therapy.
AB  - Acne vulgaris is classically considered a disease of adolescence. Although it
      most commonly occurs and has been best studied in that age group, it can develop
      at any time during childhood. It is important that health care practitioners
      recognize the manifestations of neonatal, infantile and childhood acne, as well
      as the differential diagnosis and best therapeutic approach in the younger child.
      Acneiform eruptions in infants and toddlers can occasionally be associated with
      scarring or with other significant disorders that may be life-threatening. In
      this article, the authors draw on their own clinical experience as well as the
      available literature to suggest an age-based approach to managing acne in
      children from the neonatal period through age 11 years.

PMID- 21943567
TI  - Environmental and economic profile of six typologies of wastewater treatment
      plants.
AB  - The objective of wastewater treatment plants (WWTPs) is to prevent pollution.
      However, it is necessary to assess their sustainability in order to ensure that
      pollution is being removed, not displaced. In this research, the performance of
      24 WWTPs has been evaluated using a streamlined Life Cycle Assessment (LCA) with
      Eutrophication Potential (EP) and Global Warming Potential (GWP) as environmental
      indicators, and operational costs as economic indicators. WWTPs were further
      classified in six typologies by their quality requirements according to their
      final discharge point or water reuse. Moreover, two different functional units
      (FU), one based on volume (m(3)) and the other on eutrophication reduction (kg
      PO(4)(3-) removed) were used to further determine sustainability. A correlation
      between legal requirements and technologies used to achieve them was found:
      Organic matter removal plants were found to be less costly both in environmental
      and economic terms if volume was used as the functional unit, while more
      demanding typologies such as reuse plants showed a trade-off between lower EP and
      higher cost and GWP; however, this is overcome if the second FU is used instead,
      proving the sustainability of these options and that this FU better reflects the
      objectives of a WWTP.

PMID- 21943568
TI  - Effects of soluble and particulate substrate on the carbon and energy footprint
      of wastewater treatment processes.
AB  - Most wastewater treatment plants monitor routinely carbonaceous and nitrogenous
      load parameters in influent and effluent streams, and often in the intermediate
      steps. COD fractionation discriminates the selective removal of VSS components in
      different operations, allowing accurate quantification of the energy requirements
      and mass flows for secondary treatment, sludge digestion, and sedimentation. We
      analysed the different effects of COD fractions on carbon and energy footprint in
      a wastewater treatment plant with activated sludge in nutrient removal mode and
      anaerobic digestion of the sludge with biogas energy recovery. After presenting a
      simple rational procedure for COD and solids fractions quantification, we use our
      carbon and energy footprint models to quantify the effects of varying fractions
      on carbon equivalent flows, process energy demand and recovery. A full-scale real
      process was modelled with this procedure and the results are reported in terms of
      energy and carbon footprint. For a given process, the increase of the ratio
      sCOD/COD increases the energy demand on the aeration reactors, the associated
      CO(2) direct emission from respiration, and the indirect emission for power
      generation. Even though it appears as if enhanced primary sedimentation is a
      carbon and energy footprint mitigation practice, care must be used since the
      nutrient removal process downstream may suffer from an excessive bCOD removal and
      an increased mean cell retention time for nutrient removal may be required.

PMID- 21943569
TI  - Optimization of intermittent, simultaneous dosage of nitrite and hydrochloric
      acid to control sulfide and methane productions in sewers.
AB  - Free nitrous acid (FNA) was previously demonstrated to be biocidal to anaerobic
      sewer biofilms. The intermittent dosing of FNA as a measure for controlling
      sulfide and methane productions in sewers is investigated. The impact of three
      key operational parameters namely the dosing concentration, dosing duration and
      dosing interval on the suppression and subsequent recovery of sulfide and methane
      production was examined experimentally using lab-scale sewer reactors. FNA as low
      as 0.26 mg-N/L was able to suppress sulfide production after an exposure of 12h.
      In comparison, 0.09 mg-N/L of FNA with 6-h exposure was adequate to restrain
      methanogenesis effectively. The recovery of sulfide production was well described
      by an exponential recovery equation. Model-based analysis revealed that 12-h
      dosage at an FNA concentration of 0.26 mg-N/L every 5 days can reduce the average
      sulfide production by >80%. Economic analysis showed that intermittent FNA dosage
      is potentially a cost-effective strategy for sulfide and methane control in
      sewers.

PMID- 21943570
TI  - SAFL Baffle retrofit for suspended sediment removal in storm sewer sumps.
AB  - Standard sumps (manholes) provide a location for pipe junctions and maintenance
      access in stormwater drainage systems. Standard sumps can also remove sand and
      silt particles from stormwater, but have a high propensity for washout of the
      collected sediment. With appropriate maintenance these sumps may qualify as a
      stormwater best management practice (BMP) device for the removal of suspended
      sediment from stormwater runoff. To decrease the maintenance frequency and
      prevent standard sumps from becoming a source of suspended sediment under high
      flow conditions, a porous baffle, named the SAFL Baffle, has been designed and
      tested as a retrofit to the sump. Multiple configurations with varying percent
      open area and different angles of attack were evaluated in scale models. An
      optimum configuration was then constructed at the prototype scale and evaluated
      for both removal efficiency and washout. Results obtained with the retrofit
      indicate that with the right baffle dimensions and porosity, sediment washout
      from the sump at high flow rates can be almost eliminated, and removal efficiency
      can be significantly increased at low flow rates. Removal efficiency and washout
      functions have been developed for standard sumps retrofitted with the SAFL
      Baffle. The results of this research provide a new, versatile stormwater
      treatment device and implemented new washout and removal efficiency testing
      procedures that will improve research and development of stormwater treatment
      devices.

PMID- 21943571
TI  - Mean intensity curve on dynamic contrast-enhanced susceptibility-weighted
      perfusion MR imaging--review of a new parameter to differentiate intracranial
      tumors.
AB  - Dynamic susceptibility contrast (DSC) perfusion imaging has been in clinical use
      for various indications, including characterization and grading of intracranial
      neoplasms. However, several technical factors can lead to pitfalls in image
      interpretation. This review discusses the extraction of T1 and T2* information
      from mean curve analysis of DSC perfusion imaging of various brain tumors, which
      provides further insights into tumor biology and, thus, may be useful in the
      differential diagnosis of such tumors. Indeed, by looking at the mean time-signal
      intensity curve from the tumor bed in addition to the rCBV maps, it is possible
      to obtain further inferences of capillary density and lesion leakiness. When
      dynamic contrast enhanced (DCE) T1 perfusion is not available, DSC perfusion with
      mean curve analysis appears to be a valid alternative for characterizing various
      brain neoplasms in a routine clinical setting.

PMID- 21943572
TI  - Abdominal lump in an old woman. Spigelian hernia.

PMID- 21943573
TI  - An analysis of the significant decline in motor vehicle traffic fatalities in
      2008.

PMID- 21943574
TI  - Commentary: driven to success.

PMID- 21943575
TI  - Women in white.

PMID- 21943576
TI  - Procedural sedation: is two better than one? Answers to the May 2011 Journal Club
      questions.

PMID- 21943577
TI  - Young man with skin discoloration. Acute radiation syndrome caused by exposure to
      radioactive cobalt.

PMID- 21943578
TI  - Diagnostic imaging and the clinical practice model of emergency medicine.

PMID- 21943580
TI  - Treatment of VIPs.

PMID- 21943581
TI  - Lean is a tool in the toolbox, not the silver bullet.

PMID- 21943584
TI  - Notes on tracheal intubation with indirect laryngoscopes.

PMID- 21943585
TI  - Definition of an emergency physician. Policy statement.

PMID- 21943586
TI  - Alternative methods to vascular access in the emergency department. Policy
      statement.

PMID- 21943587
TI  - Conflict of interest. Policy statement.

PMID- 21943588
TI  - Protection from physical violence in the emergency department environment. Policy
      statement.

PMID- 21943589
TI  - Leadership in emergency medical services. Policy statement.

PMID- 21943590
TI  - Elderly male with mesogastric pain. Small bowel obstruction caused by an intact
      fresh grape.

PMID- 21943591
TI  - Changing epidemiological trends of legionellosis in New Zealand, 1979-2009.
AB  - This study evaluated the spatio-temporal variation of Legionella spp. in New
      Zealand using notification and laboratory surveillance data from 1979 to 2009 and
      analysed the epidemiological trends. To achieve this we focused on changing
      incidence rates and occurrence of different species over this time. We also
      examined whether demographic characteristics such as ethnicity may be related to
      incidence. The annual incidence rate for laboratory-proven cases was 2.5/100,000
      and 1.4/100,000 for notified cases. Incidence was highest in the European
      population and showed large geographical variations between 21 District Health
      Boards. An important finding of this study is that the predominant Legionella
      species causing disease in New Zealand differs from that found in other developed
      countries, with about 30-50% of cases due to L. longbeachae and a similar
      percentage due to L. pneumophila for any given year. The environmental risk
      exposure was identified in 420 (52%) cases, of which 58% were attributed to
      contact with compost; travel was much less significant as a risk factor (6.5%).
      This suggests that legionellosis has a distinctive epidemiological pattern in New
      Zealand.

PMID- 21943592
TI  - Electrospun poly(L-lactic acid) nanofibres loaded with dexamethasone to induce
      osteogenic differentiation of human mesenchymal stem cells.
AB  - Dexamethasone (Dex), a synthetic corticosteroid, was loaded into poly(L-lactic
      acid) (PLLA) nanofibrous scaffolds with a concentration of 0.333 wt% by
      electrospinning. The Dex-loaded PLLA nanofibres increased the mechanical strength
      in comparison with pure PLLA nanofibres. A sustained release profile for over 2
      months with an initial burst release after 12 h of 17% was shown. Importantly,
      the amounts of Dex released from the PLLA nanofibres every 3 days were close to
      the ones used for the standard osteogenic medium. The sustained osteoinductive
      environment created by released Dex strongly differentiated human mesenchymal
      stem cells (hMSCs) cultured in the Ost(-Dex) medium. ALP activity, BSP expression
      and calcium deposition were significantly higher than those of the cells cultured
      on the PLLA scaffolds without Dex. A large amount of hydroxyapatite-like minerals
      was observed on the Dex-loaded PLLA scaffolds after 21 days culture. The cells on
      these scaffolds also indicated an osteoblastic morphology on the 14th day.
      Besides, these scaffolds slightly increased the cell proliferation comparing to
      the scaffolds without Dex. As such, the PLLA nanofibres loaded with 0.333 wt% Dex
      was an effective osteoinductive scaffold which acts as a promising strategy for
      bone treatment. 

PMID- 21943593
TI  - Wnt signaling as a potential therapeutic target for frontotemporal dementia.
AB  - Progranulin mutations result in frontotemporal dementia, but the underlying
      pathophysiology has remained largely unexplained. New data by Geschwind and
      colleagues in this issue of Neuron uncovered that the Wnt/FZD2 signaling pathway
      is an early and critical contributor to disease pathology.

PMID- 21943594
TI  - Patterning spinal motor activity in the absence of synaptic excitation.
AB  - Alternate activation of antagonistic muscles across a joint is essential for
      movement. A new study, by Talpalar et al., in this issue of Neuron highlights the
      importance of spinal cord inhibitory interneurons in generating motor activity by
      showing that they can generate alternating flexor-extensor motor neuron firing in
      the absence of glutamatergic synaptic input.

PMID- 21943595
TI  - The dynamics of learning and behavioral flexibility.
AB  - Fundamental to behavior is the capacity to distinguish beneficial from
      detrimental environmental stimuli. In this issue of Neuron, a new study by
      Morrison et al. shows that underlying these processes are qualitatively different
      dynamical interactions between brain structures involved in processing the value
      of environmental stimuli.

PMID- 21943596
TI  - All in a sniff: olfaction as a model for active sensing.
AB  - Sensation is an active process involving the sampling and central processing of
      external stimuli selectively in space and time. Olfaction in particular depends
      strongly on active sensing due to the fact that-at least in mammals-inhalation of
      air into the nasal cavity is required for odor detection. This seemingly simple
      first step in odor sensation profoundly shapes nearly all aspects of olfactory
      system function, from the distribution of odorant receptors to the functional
      organization of central processing to the perception of odors. The dependence of
      olfaction on inhalation also allows for profound modulation of olfactory
      processing by changes in odor sampling strategies in coordination with
      attentional state and sensory demands. This review discusses the role of active
      sensing in shaping olfactory system function at multiple levels and draws
      parallels with other sensory modalities to highlight the importance of an active
      sensing perspective in understanding how sensory systems work in the behaving
      animal.

PMID- 21943597
TI  - Seeing things in motion: models, circuits, and mechanisms.
AB  - Motion vision provides essential cues for navigation and course control as well
      as for mate, prey, or predator detection. Consequently, neurons responding to
      visual motion in a direction-selective way are found in almost all species that
      see. However, directional information is not explicitly encoded at the level of a
      single photoreceptor. Rather, it has to be computed from the spatio-temporal
      excitation level of at least two photoreceptors. How this computation is done and
      how this computation is implemented in terms of neural circuitry and membrane
      biophysics have remained the focus of intense research over many decades. Here,
      we review recent progress made in this area with an emphasis on insects and the
      vertebrate retina.

PMID- 21943599
TI  - Development of cell type-specific connectivity patterns of converging excitatory
      axons in the retina.
AB  - To integrate information from different presynaptic cell types, dendrites receive
      distinct patterns of synapses from converging axons. How different afferents in
      vivo establish specific connectivity patterns with the same dendrite is poorly
      understood. Here, we examine the synaptic development of three glutamatergic
      bipolar cell types converging onto a common postsynaptic retinal ganglion cell.
      We find that after axons and dendrites target appropriate synaptic layers,
      patterns of connections among these neurons diverge through selective changes in
      the conversion of axo-dendritic appositions to synapses. This process is
      differentially regulated by neurotransmission, which is required for the shift
      from single to multisynaptic appositions of one bipolar cell type but not for
      maintenance and elimination, respectively, of connections from the other two
      types. Thus, synaptic specificity among converging excitatory inputs in the
      retina emerges via differential synaptic maturation of axo-dendritic appositions
      and is shaped by neurotransmission in a cell type-dependent manner.

PMID- 21943598
TI  - A resource of Cre driver lines for genetic targeting of GABAergic neurons in
      cerebral cortex.
AB  - A key obstacle to understanding neural circuits in the cerebral cortex is that of
      unraveling the diversity of GABAergic interneurons. This diversity poses general
      questions for neural circuit analysis: how are these interneuron cell types
      generated and assembled into stereotyped local circuits and how do they
      differentially contribute to circuit operations that underlie cortical functions
      ranging from perception to cognition? Using genetic engineering in mice, we have
      generated and characterized approximately 20 Cre and inducible CreER knockin
      driver lines that reliably target major classes and lineages of GABAergic
      neurons. More select populations are captured by intersection of Cre and Flp
      drivers. Genetic targeting allows reliable identification, monitoring, and
      manipulation of cortical GABAergic neurons, thereby enabling a systematic and
      comprehensive analysis from cell fate specification, migration, and connectivity,
      to their functions in network dynamics and behavior. As such, this approach will
      accelerate the study of GABAergic circuits throughout the mammalian brain.

PMID- 21943600
TI  - Regulation of AMPA receptor function by the human memory-associated gene KIBRA.
AB  - KIBRA has recently been identified as a gene associated with human memory
      performance. Despite the elucidation of the role of KIBRA in several diverse
      processes in nonneuronal cells, the molecular function of KIBRA in neurons is
      unknown. We found that KIBRA directly binds to the protein interacting with C
      kinase 1 (PICK1) and forms a complex with alpha-amino-3-hydroxyl-5-methyl-4
      isoxazole-propionate receptors (AMPARs), the major excitatory neurotransmitter
      receptors in the brain. KIBRA knockdown accelerates the rate of AMPAR recycling
      following N-methyl-D-aspartate receptor-induced internalization. Genetic deletion
      of KIBRA in mice impairs both long-term depression and long-term potentiation at
      hippocampal Schaffer collateral-CA1 synapses. Moreover, KIBRA knockout mice have
      severe deficits in contextual fear learning and memory. These results indicate
      that KIBRA regulates higher brain function by regulating AMPAR trafficking and
      synaptic plasticity.

PMID- 21943601
TI  - Functional genomic analyses identify pathways dysregulated by progranulin
      deficiency, implicating Wnt signaling.
AB  - Progranulin (GRN) mutations cause frontotemporal dementia (FTD), but GRN's
      function in the CNS remains largely unknown. To identify the pathways downstream
      of GRN, we used weighted gene coexpression network analysis (WGCNA) to develop a
      systems-level view of transcriptional alterations in a human neural progenitor
      model of GRN-deficiency. This highlighted key pathways such as apoptosis and
      ubiquitination in GRN deficient human neurons, while revealing an unexpected
      major role for the Wnt signaling pathway, which was confirmed by analysis of gene
      expression data from postmortem FTD brain. Furthermore, we observed that the Wnt
      receptor Fzd2 was one of only a few genes upregulated at 6 weeks in a GRN
      knockout mouse, and that FZD2 reduction caused increased apoptosis, while its
      upregulation promoted neuronal survival in vitro. Together, these in vitro and in
      vivo data point to an adaptive role for altered Wnt signaling in GRN deficiency
      mediated FTD, representing a potential therapeutic target.

PMID- 21943602
TI  - Axon regeneration pathways identified by systematic genetic screening in C.
      elegans.
AB  - The mechanisms underlying the ability of axons to regrow after injury remain
      poorly explored at the molecular genetic level. We used a laser injury model in
      Caenorhabditis elegans mechanosensory neurons to screen 654 conserved genes for
      regulators of axonal regrowth. We uncover several functional clusters of genes
      that promote or repress regrowth, including genes classically known to affect
      axon guidance, membrane excitability, neurotransmission, and synaptic vesicle
      endocytosis. The conserved Arf Guanine nucleotide Exchange Factor (GEF), EFA-6,
      acts as an intrinsic inhibitor of regrowth. By combining genetics and in vivo
      imaging, we show that EFA-6 inhibits regrowth via microtubule dynamics,
      independent of its Arf GEF activity. Among newly identified regrowth inhibitors,
      only loss of function in EFA-6 partially bypasses the requirement for DLK-1
      kinase. Identification of these pathways significantly expands our understanding
      of the genetic basis of axonal injury responses and repair.

PMID- 21943603
TI  - GDE2 regulates subtype-specific motor neuron generation through inhibition of
      Notch signaling.
AB  - The specification of spinal interneuron and motor neuron identities initiates
      within progenitor cells, while motor neuron subtype diversification is regulated
      by hierarchical transcriptional programs implemented postmitotically. Here we
      find that mice lacking GDE2, a six-transmembrane protein that triggers motor
      neuron generation, exhibit selective losses of distinct motor neuron subtypes,
      specifically in defined subsets of limb-innervating motor pools that correlate
      with the loss of force-generating alpha motor neurons. Mechanistically, GDE2 is
      expressed by postmitotic motor neurons but utilizes extracellular
      glycerophosphodiester phosphodiesterase activity to induce motor neuron
      generation by inhibiting Notch signaling in neighboring motor neuron progenitors.
      Thus, neuronal GDE2 controls motor neuron subtype diversity through a non-cell
      autonomous feedback mechanism that directly regulates progenitor cell
      differentiation, implying that subtype specification initiates within motor
      neuron progenitor populations prior to their differentiation into postmitotic
      motor neurons.

PMID- 21943604
TI  - Identification of minimal neuronal networks involved in flexor-extensor
      alternation in the mammalian spinal cord.
AB  - Neural networks in the spinal cord control two basic features of locomotor
      movements: rhythm generation and pattern generation. Rhythm generation is
      generally considered to be dependent on glutamatergic excitatory neurons. Pattern
      generation involves neural circuits controlling left-right alternation, which has
      been described in great detail, and flexor-extensor alternation, which remains
      poorly understood. Here, we use a mouse model in which glutamatergic
      neurotransmission has been ablated in the locomotor region of the spinal cord.
      The isolated in vitro spinal cord from these mice produces locomotor-like
      activity-when stimulated with neuroactive substances-with prominent flexor
      extensor alternation. Under these conditions, unlike in control mice, networks of
      inhibitory interneurons generate the rhythmic activity. In the absence of
      glutamatergic synaptic transmission, the flexor-extensor alternation appears to
      be generated by Ia inhibitory interneurons, which mediate reciprocal inhibition
      from muscle proprioceptors to antagonist motor neurons. Our study defines a
      minimal inhibitory network that is needed to produce flexor-extensor alternation
      during locomotion.

PMID- 21943605
TI  - Distinct modes of AMPA receptor suppression at developing synapses by GluN2A and
      GluN2B: single-cell NMDA receptor subunit deletion in vivo.
AB  - During development there is an activity-dependent switch in synaptic N-Methyl-D
      aspartate (NMDA) receptor subunit composition from predominantly GluN2B to
      GluN2A, though the precise role of this switch remains unknown. By deleting GluN2
      subunits in single neurons during synaptogenesis, we find that both GluN2B and
      GluN2A suppress AMPA receptor expression, albeit by distinct means. Similar to
      GluN1, GluN2B deletion increases the number of functional synapses, while GluN2A
      deletion increases the strength of unitary connections without affecting the
      number of functional synapses. We propose a model of excitatory synapse
      maturation in which baseline activation of GluN2B-containing receptors prevents
      premature synapse maturation until correlated activity allows induction of
      functional synapses. This activity also triggers the switch to GluN2A, which
      dampens further potentiation. Furthermore, we analyze the subunit composition of
      synaptic NMDA receptors in CA1 pyramidal cells, provide electrophysiological
      evidence for a large population of synaptic triheteromeric receptors, and
      estimate the subunit-dependent open probability.

PMID- 21943606
TI  - DPP6 establishes the A-type K(+) current gradient critical for the regulation of
      dendritic excitability in CA1 hippocampal neurons.
AB  - Subthreshold-activating A-type K(+) currents are essential for the proper
      functioning of the brain, where they act to delay excitation and regulate firing
      frequency. In CA1 hippocampal pyramidal neuron dendrites, the density of A-type
      K(+) current increases with distance from the soma, playing an important role in
      synaptic integration and plasticity. The mechanism underlying this gradient has,
      however, remained elusive. Here, dendritic recordings from mice lacking the Kv4
      transmembrane auxiliary subunit DPP6 revealed that this protein is critical for
      generating the A-current gradient. Loss of DPP6 led to a decrease in A-type
      current, specifically in distal dendrites. Decreased current density was
      accompanied by a depolarizing shift in the voltage dependence of channel
      activation. Together these changes resulted in hyperexcitable dendrites with
      enhanced dendritic AP back-propagation, calcium electrogenesis, and induction of
      synaptic long-term potentiation. Despite enhanced dendritic excitability, firing
      behavior evoked by somatic current injection was mainly unaffected in DPP6-KO
      recordings, indicating compartmentalized regulation of neuronal excitability.

PMID- 21943607
TI  - Vesicular zinc promotes presynaptic and inhibits postsynaptic long-term
      potentiation of mossy fiber-CA3 synapse.
AB  - The presence of zinc in glutamatergic synaptic vesicles of excitatory neurons of
      mammalian cerebral cortex suggests that zinc might regulate plasticity of
      synapses formed by these neurons. Long-term potentiation (LTP) is a form of
      synaptic plasticity that may underlie learning and memory. We tested the
      hypothesis that zinc within vesicles of mossy fibers (mf) contributes to mf-LTP,
      a classical form of presynaptic LTP. We synthesized an extracellular zinc
      chelator with selectivity and kinetic properties suitable for study of the large
      transient of zinc in the synaptic cleft induced by mf stimulation. We found that
      vesicular zinc is required for presynaptic mf-LTP. Unexpectedly, vesicular zinc
      also inhibits a form of postsynaptic mf-LTP. Because the mf-CA3 synapse provides
      a major source of excitatory input to the hippocampus, regulating its efficacy by
      these dual actions, vesicular zinc is critical to proper function of hippocampal
      circuitry in health and disease.

PMID- 21943608
TI  - Different time courses for learning-related changes in amygdala and orbitofrontal
      cortex.
AB  - The orbitofrontal cortex (OFC) and amygdala are thought to participate in
      reversal learning, a process in which cue-outcome associations are switched.
      However, current theories disagree on whether OFC directs reversal learning in
      the amygdala. Here, we show that during reversal of cues' associations with
      rewarding and aversive outcomes, neurons that respond preferentially to stimuli
      predicting aversive events update more quickly in amygdala than OFC; meanwhile,
      OFC neurons that respond preferentially to reward-predicting stimuli update more
      quickly than those in the amygdala. After learning, however, OFC consistently
      differentiates between impending reinforcements with a shorter latency than the
      amygdala. Finally, analysis of local field potentials (LFPs) reveals a
      disproportionate influence of OFC on amygdala that emerges after learning. We
      propose that reversal learning is supported by complex interactions between
      neural circuits spanning the amygdala and OFC, rather than directed by any single
      structure.

PMID- 21943609
TI  - Hedging your bets by learning reward correlations in the human brain.
AB  - Human subjects are proficient at tracking the mean and variance of rewards and
      updating these via prediction errors. Here, we addressed whether humans can also
      learn about higher-order relationships between distinct environmental outcomes, a
      defining ecological feature of contexts where multiple sources of rewards are
      available. By manipulating the degree to which distinct outcomes are correlated,
      we show that subjects implemented an explicit model-based strategy to learn the
      associated outcome correlations and were adept in using that information to
      dynamically adjust their choices in a task that required a minimization of
      outcome variance. Importantly, the experimentally generated outcome correlations
      were explicitly represented neuronally in right midinsula with a learning
      prediction error signal expressed in rostral anterior cingulate cortex. Thus, our
      data show that the human brain represents higher-order correlation structures
      between rewards, a core adaptive ability whose immediate benefit is optimized
      sampling.

PMID- 21943611
TI  - Correspondence re "Association of manual muscle tests and mechanical neck pain:
      results from a prospective pilot study".

PMID- 21943613
TI  - Changes in pain and pressure pain sensitivity after manual treatment of active
      trigger points in patients with unilateral shoulder impingement: a case series.
AB  - The aim of this case series was to investigate changes in pain and pressure pain
      sensitivity after manual treatment of active trigger points (TrPs) in the
      shoulder muscles in individuals with unilateral shoulder impingement. Twelve
      patients (7 men, 5 women, age: 25 +/- 9 years) diagnosed with unilateral shoulder
      impingement attended 4 sessions for 2 weeks (2 sessions/week). They received TrP
      pressure release and neuromuscular interventions over each active TrP that was
      found. The outcome measures were pain during arm elevation (visual analogue
      scale, VAS) and pressure pain thresholds (PPT) over levator scapulae,
      supraspinatus infraspinatus, pectoralis major, and tibialis anterior muscles.
      Pain was captured pre-intervention and at a 1-month follow-up, whereas PPT were
      assessed pre- and post-treatment, and at a 1-month follow-up. Patients
      experienced a significant (P < 0.001) reduction in pain after treatment (mean +/-
      SD: 1.3 +/- 0.5) with a large effect size (d > 1). In addition, patients also
      experienced a significant increase in PPT immediate after the treatment (P <
      0.05) and one month after discharge (P < 0.01), with effect sizes ranging from
      moderate (d = 0.4) to large (d > 1).A significant negative association (r(s) = 
      0.525; P = 0.049) between the increase in PPT over the supraspinatus muscle and
      the decrease in pain was found: the greater the decrease in pain, the greater the
      increase in PPT. This case series has shown that manual treatment of active
      muscle TrPs can help to reduce shoulder pain and pressure sensitivity in shoulder
      impingement. Current findings suggest that active TrPs in the shoulder
      musculature may contribute directly to shoulder complaint and sensitization in
      patients with shoulder impingement syndrome, although future randomized
      controlled trials are required.

PMID- 21943614
TI  - Fascial release effects on patients with non-specific cervical or lumbar pain.
AB  - BACKGROUND: Myofascial Release (MFR) and Fascial Unwinding (FU) are widely used
      manual fascial techniques (MFTs), generally incorporated in treatment protocols
      to release fascial restrictions and restore tissue mobility. However, the effects
      of MFT on pain perception, and the mobility of fascial layers, have not
      previously been investigated using dynamic ultrasound (US) in patients with neck
      pain (NP) and low back pain (LBP). OBJECTIVES: a) To show that US screening can
      be a useful tool to assess dysfunctional alteration of organ mobility in relation
      to their fascial layers, in people with non-specific NP or LBP, in the absence of
      any organ disease; b) To assess, by dynamic US screening, the change of sliding
      movements between superficial and deep fascia layers in the neck, in people with
      non-specific NP, before and after application of MFTs c) To assess, by dynamic US
      screening, the variation of right reno-diaphragmatic (RD) distance and of neck
      bladder (NB) mobility, in patients with non-specific LBP, before and after
      application of MFTs d) To evaluate 'if' and 'at what degree' pain perception may
      vary in patients with NP or LBP, after MFTs are applied, over the short term.
      METHODS: An Experimental group of 60 subjects, 30 with non-specific NP and 30
      with non-specific LBP, were assessed in the area of complaint, by Dynamic
      Ultrasound Topographic Anatomy Evaluation (D.US.T.A.-E.), before and after MFTs
      were applied in situ, in the corresponding painful region, for not more than 12
      min. The results were compared with those from the respective Sham-Control group
      of 30 subjects. For the NP sub-groups, the pre- to post- US recorded videos of
      each subject were compared and assessed randomly and independently by two blinded
      experts in echographic screening. They were asked to rate the change observed in
      the cervical fascia sliding motions as 'none', 'discrete' or 'radical'. For the
      LBP sub-groups, a pre- to post- variation of the right RD distances and NB
      mobility were calculated on US imaging and compared. For all four sub-groups, a
      Short-Form McGill Pain Assessment Questionnaire (SF-MPQ) was administered on the
      day of recruitment as well as on the third day following treatment. RESULTS: The
      Chi square test has shown a significant correlation (0.915) with a p-Value <
      0.0001 between the two examiners' results on US videos in NP sub-groups. The
      ANOVA test at repeated measures has shown a significant difference (p-Value <
      0.0001) within Experimental and Control groups for the a) pre- to post- RD
      distances in LBP sub-groups, b) pre- to post- NB distances in LBP sub-groups; as
      well as between groups as for c) pre- to post- SF-MPQ results in NP and LBP sub
      groups. CONCLUSIONS: Dynamic US evaluation can be a valid and non-invasive
      instrument to assess and monitor effective sliding motion of fascial layers in
      vivo. MFTs are effective manual techniques to release area of impaired sliding
      fascial mobility, and to improve pain perception over a short term duration in
      people with non-specific NP or LBP.

PMID- 21943615
TI  - The assessment of the cervical spine. Part 2: strength and endurance/fatigue.
AB  - Quantitative documentation of physical deficits such as muscle strength and
      endurance/fatigue in the cervical spine may provide objective information, not
      only helping the diagnostic procedures, but also monitoring rehabilitation
      progress and documenting permanent impairments. The reliable and valid evaluation
      of muscle strength and endurance both in clinical and research environments are a
      difficult task since there are many factors that could affect the assessment
      procedure and the obtained values. The aim of the second part of this critical
      review is to identify the factors influencing the assessment of strength and
      endurance/fatigue of the muscles in the cervical spine.

PMID- 21943616
TI  - Effectiveness of direct vs indirect technique myofascial release in the
      management of tension-type headache.
AB  - BACKGROUND: Tension-type headache (TTH) is essentially defined as bilateral
      headache of a pressing or tightening quality without a known medical cause.
      Myofascial release (MFR) is currently being applied for patients with TTH but its
      efficacy has not been evaluated formally. OBJECTIVE: To investigate whether
      direct technique myofascial release (DT-MFR) reduces the frequency of headache
      more effectively than the indirect technique myofascial release (IDT-MFR) in
      comparison to a Control Group receiving slow soft stroking. DESIGN: Randomized,
      controlled, single blinded trial. SETTING: The clinical wing of Myofascial
      Therapy and Research Foundation, Kerala, India. PARTICIPANTS: 63 patients with
      episodic or chronic tension-type headache. INTERVENTIONS: DT-MFR, IDT-MFR or
      Control. The techniques were administered by certified myofascial release
      practitioners and consisted of 24 sessions per patient over 12 weeks. MAIN
      OUTCOME MEASURE: Difference in numbers of days with headache between Weeks 1-4
      (i.e. 4 weeks prior to start of Intervention) and Weeks 17-20, following 12 weeks
      of Intervention between Weeks 5-16 as recorded by participants in headache
      diaries. RESULTS: The number of days with headache per 4 weeks decreased by 7.1
      (2.6) [mean (SD)] days in the DT-MFR group compared with 6.7 (1.8) days in the
      IDT-MFR group and 1.6 (0.5) days in the control group, (P < 0.001). Patients in
      the DT-MFR Group, IDT-MFR Group and Control Group reported a 59.2%, 54% and 13.3%
      reduction in their headache frequency in Weeks 17-20 compared to that in Weeks 1
      4. CONCLUSIONS: This study provides evidence that Direct Technique or Indirect
      Technique Myofascial Release is more effective than the Control Intervention for
      tension headache.

PMID- 21943617
TI  - The use of abdominal massage to treat chronic constipation.
AB  - Constipation is a disorder of gastrointestinal motility characterized by
      difficult or decreased bowel movements, and is a common condition in Western
      countries. Laxatives are the most common strategy for managing constipation.
      However, long-term use of some laxatives may be associated with harmful side
      effects including increased constipation and fecal impaction. Abdominal massage,
      once an accepted method of treating constipation, is no longer standard of care,
      but may be a desirable therapy for this condition because it is inexpensive, non
      invasive, free of harmful side-effects, and can be performed by patients
      themselves. However, until recently, evidence for its effectiveness was not
      strong enough to make a recommendation for its use in constipated patients. In
      1999, Ernst reviewed all available controlled clinical trials, and found that
      there was no sound evidence for the effectiveness of abdominal massage in the
      treatment of chronic constipation. This article reviews scientific evidence from
      1999 to the present, regarding abdominal massage as an intervention for chronic
      constipation. Since that time, studies have demonstrated that abdominal massage
      can stimulate peristalsis, decrease colonic transit time, increase the frequency
      of bowel movements in constipated patients, and decrease the feelings of
      discomfort and pain that accompany it. There is also good evidence that massage
      can stimulate peristalsis in patients with post-surgical ileus. Individual case
      reports show that massage has been effective for patients with constipation due
      to a variety of diagnosed physiologic abnormalities, as well as in patients with
      long-term functional constipation.

PMID- 21943618
TI  - Does the Feldenkrais Method make a difference? An investigation into the use of
      outcome measurement tools for evaluating changes in clients.
AB  - Evidence-based practice confirms the need for outcome measures. Feldenkrais
      Method practitioners struggle to use such tools because of the broad range of
      applications of the Feldenkrais Method and the difficulty identifying suitable
      measurement tools. A pre/post-test design was used to investigate the use of
      three outcome measurement tools [Patient-specific Functional Scale (PSFS), Pain
      Outcome Profile (POP) and Short Form12v2 Health questionnaire (SF12v2)] for
      clients experiencing problems performing everyday functional tasks who attended
      Feldenkrais sessions. Eleven Feldenkrais practitioners submitted data on 48
      clients. Changes were detected in the clients' ability to perform everyday tasks
      (PSFS improved 3.8 points, p < 0.001), levels of pain decreased (POP improved in
      current pain p = 0.001, physical index p < 0.001 and affective index p = 0.001)
      and quality of life improved significantly in six of the eight SF12v2 domains.
      These three tools have been found to be suitable for detecting changes in client
      function before and after a series of Feldenkrais sessions.

PMID- 21943619
TI  - Real-time stability measurement system for postural control.
AB  - A method for assessing balance, which was sensitive to changes in the postural
      control system is presented. This paper describes the implementation of a force
      sensing platform, with force sensing resistors as the sensing element. The
      platform is capable of measuring destabilized postural perturbations in dynamic
      and static postural conditions. Besides providing real-time qualitative
      assessment, the platform quantifies the postural control of the subjects. This is
      done by evaluating the weighted center of applied pressure distribution over
      time. The objective of this research was to establish the feasibility of using
      the force-sensing platform to test and gauge the postural control of individuals.
      Tests were conducted in Eye Open and Eye Close states on Flat Ground (static
      condition) and the balance trainer (dynamic condition). It was observed that the
      designed platform was able to gauge the sway experienced by the body when
      subject's states and conditions changed.

PMID- 21943620
TI  - Application of rehabilitative ultrasound in the assessment of low back pain: a
      literature review.
AB  - Low back pain (LBP) is one of the most common work-related conditions affecting
      all populations both in industrialized and non-industrialized countries, with
      reported high prevalence and incidence rates and huge direct and indirect costs.
      Among various suggested causes of LBP, dysfunction of back muscles, particularly
      lumbar multifidus and transverse abdominis, has been the subject of considerable
      research during last decades. Of the available imaging techniques, ultrasound
      (US) imaging technique is increasingly used to assess muscle dimensions and
      function as a valid, reliable and non-invasive approach. The purpose of the
      present study was to review the previously published studies (1990-2009)
      concerning the merit of US imaging of lumbar and abdominal muscles with
      particular attention to its clinical application in patients with LBP. Studies
      showed wide variation in terms of methodology, sample size, procedure, definition
      of LBP, heterogeneous sample, method of analyzing US imaging, US imaging
      parameters, etc. However, a convincing body of evidence was identified that
      supports US imaging as a reliable and valid tool both to differentiate patients
      with LBP from normal subjects and to monitor the effect of rehabilitation
      programs.

PMID- 21943621
TI  - Influence of heat on fatigue and electromyographic activity of the biceps brachii
      muscle.
AB  - Electromyography enables registering muscle activity during contraction and can
      identify muscle fatigue. In the present study, 30 volunteers between 18 and 30
      years of age were submitted to an exertion 1 min of maximal voluntary isometric
      contraction. The electromyographic signal of the biceps brachii muscle and the
      strength of the flexor muscles of the elbow were determined before and after the
      administration of microwave diathermy in order to analyze the influence of heat
      over the strength of the elbow flexor muscles and fatigue of the biceps brachii.
      The results demonstrate that the strength of the elbow flexor muscles diminished
      significantly following the application of heat (p<0.05). Heat also led to a
      significant reduction in the electrical activity of the muscle studied. The
      present study demonstrates that microwave diathermy on the biceps brachii muscle
      reduces the flexion strength of the elbow as well as signs of muscle fatigue in
      the biceps.

PMID- 21943622
TI  - The influence of kinesiophobia on trunk muscle voluntary responses with pre
      programmed reactions during perturbation in patients with chronic low back pain.
AB  - The purpose of this study was to examine the relation between fear of movement
      and perturbation induced electromyographic global trunk muscle voluntary
      responses with pre-programmed reactions among persons with chronic low back pain
      (CLBP). CLBP subjects (n = 25) were challenged to unexpected and expected
      perturbations on stable and unstable surfaces. 'Tampa scale for kinesiophobia -
      Adjusted version-13' was used to measure kinesiophobia. Regression analysis
      revealed significant negative correlation between kinesiophobia scores and
      voluntary responses of rectus abdominis (RA) for unexpected perturbations on
      stable (r = -0.69, 95% of CI: -0.85 to -0.40, p < 0.000, r(2) = 0.41) and
      unstable surfaces (r = -0.47, 95% of CI: -0.72 to -0.09, p < 0.018, r(2) = 0.29).
      The activity of erector spinae was not influenced by most of testing conditions
      in the study except task on unstable surface for expected perturbation (r = 
      0.593, 95% of CI: -0.8 to -0.25, p = 0.002, r(2) = 0.15). RA activity and
      kinesiophobia score of the CLBP population was significantly inversely associated
      during anteriorly directed unexpected perturbations. In our study, the
      significant association between fear of movement and the trunk muscle responses
      was differentially influenced by expected and unexpected postural demands.

PMID- 21943623
TI  - Analysis of electromyographic activity of ankle muscles on stable and unstable
      surfaces with eyes open and closed.
AB  - INTRODUCTION: Proprioceptive exercises are performed on a daily basis in
      physiotherapy with the use of different unstable platforms in order to improve
      joint stability using the mechanical and sensory properties of ligaments, joint
      capsule and integrated activity of the muscles surrounding the joint. Changes in
      the myoelectrical characteristics of the muscles during activity can be
      identified using surface electromyography (EMG), which provides important
      information on the behavior of muscles submitted to different types of load.
      OBJECTIVES: The aim of the present study was to analyze the electromyographic
      activity of the tibialis anterior, tibialis posterior, peroneus longus,
      gastrocnemius lateralis and gastrocnemius medialis on stable and unstable
      surfaces with eyes open and closed. METHODOLOGY: Twenty-five active, healthy,
      male and female individuals were submitted to an anthropometric evaluation and a
      protocol involving warm up and the electromyographic assessment of muscle
      activity on different surfaces. The order of the data collection was chosen
      randomly by lots [on stable ground or unstable platforms (trampoline, balance
      platform, proprioceptive disk and proprioceptive board) with eyes open and on a
      trampoline, balance platform and stable ground with eyes closed]. The individuals
      remained balanced on these surfaces for 15 s with the knee at 30 degrees  flexion
      in order to provide greater instability. RESULTS: There was a significant
      increase (p < 0.05) in muscle activity on the unstable surfaces, with the
      exception of the trampoline, which did not achieve statistically significant
      differences in relation to the stable ground. The tibialis anterior and peroneus
      longus exhibited the greatest electromyographic activity on all surfaces. The
      proprioceptive tests performed with eyes closed exhibited significantly greater
      electromyographic activity than with eyes open. CONCLUSION: Proprioceptive
      exercises on unstable surfaces generated a significant increase in
      electromyographic activity, especially with eyes closed, and are therefore a
      valuable resource in the sensory-motor rehabilitation of the ankle.

PMID- 21943624
TI  - Reliability testing of the patellofemoral joint reaction force (PFJRF)
      measurement in taped and untaped patellofemoral conditions during single leg
      squatting: a pilot study.
AB  - INTRODUCTION: Measuring patellofemoral joint reaction forces (PFJRF) may provide
      reliable evidence for patellar taping to correct probable malalignment in
      subjects with anterior knee pain, or patellofemoral pain syndrome (PFPS). The aim
      of the present study was to examine the reliability of PFJRF measurements in
      different patellofemoral conditions during squatting in healthy subjects.
      METHODS: Using a motion analysis system and one forceplate, PFJRF of eight
      healthy subjects was assessed during single leg squatting. Data was collected
      from superficial markers taped to selected landmarks. This procedure was
      performed on the right knees, before (BT), during (WT) and shortly after patellar
      taping (SAT). The PFJRF was calculated using a biomechanical model of the
      patellofemoral joint. RESULTS: The results revealed that, there were no
      significant differences between the PFJRF mean values for three conditions of BT
      (2100.55 +/- 455.25), WT (2026.20 +/- 516.45) and SAT (2055.35 +/- 669.30) (p >
      0.05). The CV (coefficient of variation), ICC (intra class correlation
      coefficient), LSD (least significant difference) and SEM (standard error of
      measurement) values revealed the high reliability of PFJRF measurements during
      single leg squatting (p < 0.05). CONCLUSION: The high reliability of PFJRF
      measurements reveals that the future studies could rely on these measurements
      during single leg squatting.

PMID- 21943625
TI  - A prophylactic effect of proprioceptive neuromuscular facilitation (PNF)
      stretching on symptoms of muscle damage induced by eccentric exercise of the
      wrist extensors.
AB  - Stretching with proprioceptive neuromuscular facilitation (PNF) is frequently
      used before exercise. The prophylactic effect of PNF on symptoms of muscle damage
      induced by eccentric exercise of the wrist extensors was examined in this study.
      Twenty-eight healthy males were randomly divided into the PNF group (n = 14) and
      the control group (n = 14). PNF was used before eccentric exercise induction in
      the wrist extensors. All subjects were tested to examine muscle damage
      characteristics including sensory-motor functions at baseline, immediately, and
      from 1st to 8th days after the exercise-induced muscle damage (EIMD). The results
      demonstrated that the PNF group showed a lesser deficit in some sensory-motor
      functions (p < 0.05) than the control group. The prior PNF stretching application
      could be useful for attenuating the signs and symptoms of muscle damage after
      eccentric exercise.

PMID- 21943626
TI  - Influence of dynamic versus static core exercises on performance in field based
      fitness tests.
AB  - Minimal evidence supports the claim that core stability training transfers into
      improved performance and the most effective training method to perform core
      exercises is still unknown. The purpose of the study was to compare the effects
      of a 6 week unstable static versus unstable dynamic core training program, on
      field based fitness tests. A static (n = 6) and dynamic (n = 6) training group
      performed two 45 min sessions per week for six weeks. Seven performance tests,
      consisting of three core (plank; double leg lowering; back extensions), one
      static (standing stork) and three dynamic (overhead medicine ball throw; vertical
      jump; 20 m sprint), were administered pre- and post training. Between group
      differences were assessed using a repeated measures MANOVA (P < 0.05). Both
      training groups improved in each of the core tests (P < 0.05). Neither training
      group demonstrated improvement in the dynamic field based tests (medicine ball
      throw, vertical jump height and 20 m sprint) (P > 0.05). Findings indicate that
      both types of training improved specific measures of core stability but did not
      transfer into any sport-related skill.

PMID- 21943627
TI  - Stimulus and response.

PMID- 21943628
TI  - Movement therapy induced neural reorganization and motor recovery in stroke: a
      review.
AB  - This paper is a review conducted to provide an overview of accumulated evidence
      on contemporary rehabilitation methods for stroke survivors. Loss of functional
      movement is a common consequence of stroke for which a wide range of
      interventions has been developed. Traditional therapeutic approaches have shown
      limited results for motor deficits as well as lack evidence for their
      effectiveness. Stroke rehabilitation is now based on the evidence of
      neuroplasticity, which is responsible for recovery following stroke. The
      neuroplastic changes in the structure and function of relevant brain areas are
      induced primarily by specific rehabilitation methods. The therapeutic method
      which induces neuroplastic changes, leads to greater motor and functional
      recovery than traditional methods. Further, the recovery is permanent in nature.
      During the last decade various novel stroke rehabilitative methods for motor
      recovery have been developed. This review focuses on the methods that have
      evidence of associated cortical level reorganization, namely task-specific
      training, constraint-induced movement therapy, robotic training, mental imaging,
      and virtual training. All of these methods utilize principles of motor learning.
      The findings from this review demonstrated convincing evidence both at the neural
      and functional level in response to such therapies. The main aim of the review
      was to determine the evidence for these methods and their application into
      clinical practice.

PMID- 21943629
TI  - A case study utilizing Vojta/Dynamic Neuromuscular Stabilization therapy to
      control symptoms of a chronic migraine sufferer.
AB  - INTRODUCTION: Migraine is a complex disorder of the brain characterized by severe
      headache, photophobia, phonophobia, and nausea. This case report demonstrated the
      reduction of a 49-year-old female's chronic migraine symptoms after 12 weeks of
      Vojta/Dynamic Neuromuscular Stabilization (DNS) therapy. METHODS: Vojta/DNS
      treatment occurred either in the office or at home over a 12-week period.
      Symptoms were tracked via a patient diary, a VAS pain scale, and a Headache
      Disability Index (HDI). RESULTS: The patient's migraine symptoms were typically
      of 3 days duration, a frequency of 8-10 times per month, and an intensity of
      10/10 on a VAS pain scale. After a 12-week trial of Vojta/DNS care, subjective
      improvements were noted, with a reduction in frequency to 1-2 times per month,
      duration of 12 h at most, and decreased intensity to a 2/10 on a VAS pain scale.
      HDI scores dropped from 48% to 34%. DISCUSSION: This therapy reduced the patient
      migraine sysmptoms in frequency, duration and intensity. This therapy is not well
      known in North America despite its use for over 40 years in Europe. CONCLUSION:
      This case demonstrated that Vojta/DNS treatment over a 12-week period helped
      manage the patient's migraines and could be a possible treatment option for
      future research.

PMID- 21943630
TI  - Functional training with the kettlebell.

PMID- 21943631
TI  - Breath alcohol analysis incorporating standardization to water vapour is as
      precise as blood alcohol analysis.
AB  - A novel breath-alcohol analyzer based on the standardization of the breath
      alcohol concentration (BrAC) to the alveolar-air water vapour concentration has
      been developed and evaluated. The present study compares results with this
      particular breath analyzer with arterial blood alcohol concentrations (ABAC), the
      most relevant quantitative measure of brain alcohol exposure. The precision of
      analysis of alcohol in arterial blood and breath were determined as well as the
      agreement between ABAC and BrAC over time post-dosing. Twelve healthy volunteers
      were administered 0.6g alcohol/kg bodyweight via an orogastric tube. Duplicate
      breath and arterial blood samples were obtained simultaneously during the
      absorption, distribution and elimination phases of the alcohol metabolism with
      particular emphasis on the absorption phase. The precision of the breath analyzer
      was similar to the determination of blood alcohol concentration by headspace gas
      chromatography (CV 2.40 vs. 2.38%, p=0.43). The ABAC/BrAC ratio stabilized 30min
      post-dosing (2089+/-99; mean+/-SD). Before this the BrAC tended to underestimate
      the coexisting ABAC. In conclusion, breath alcohol analysis utilizing
      standardization of alcohol to water vapour was as precise as blood alcohol
      analysis, the present "gold standard" method. The BrAC reliably predicted the
      coexisting ABAC from 30min onwards after the intake of alcohol.

PMID- 21943632
TI  - Geophagia: An extraordinary cause of perforation of the sigmoid colon.

PMID- 21943633
TI  - Effects of visceral fat resection and gastric banding in an obese diabetic rat
      model.
AB  - BACKGROUND: Although the function of visceral fat has gradually become clear, the
      effects of its resection on insulin resistance and glucose metabolism are still
      unknown. This study aimed to clarify the effects of visceral fat resection and
      gastric banding in an obese diabetic rat model. METHODS: Forty male Zucker
      diabetic fatty rats were divided into 4 groups: sham operation, visceral fat
      resection, gastric banding, and gastric banding with visceral fat resection. The
      rats were followed for 8 weeks after operation, and the change in body weight,
      amount of food intake, metabolic parameters, insulin tolerance, oral glucose
      tolerance, and adipocytokines were examined. RESULTS: Compared with the sham
      operation and visceral fat resection groups, the gastric banding and gastric
      banding + visceral fat resection groups showed significant decreases in weight
      gain and cumulative food intake, as well as improvement in secretion of
      adipocytokines and in insulin resistance. Although no differences were found
      between the sham operation and visceral fat resection groups in weight gain and
      food intake, high-molecular-weight adiponectin, tumor necrosis factor-alpha
      levels, and insulin resistance were improved in the visceral fat resection group
      compared with the sham operation group. The gastric banding + visceral fat
      resection group had greater serum levels of high-molecular-weight adiponectin
      than did the gastric banding group, but no difference was found between the
      gastric banding and gastric banding + visceral fat resection groups in insulin
      resistance and glucose metabolism. CONCLUSION: In diabetic fatty rats, the
      surgical removal of visceral fat effected some improvement in insulin resistance
      and glucose metabolism. Because the effect was relatively minimal compared with
      that of gastric banding, visceral fat resection combined with gastric banding did
      not appear to exert additional effects on insulin resistance and glucose
      metabolism compared with gastric banding alone.

PMID- 21943634
TI  - Novel surgical concept in antireflux surgery: long-term outcomes comparing 3
      different laparoscopic approaches.
AB  - BACKGROUND: The Nissen fundoplication procedure is the most widely used type of
      antireflux surgery. The results are not always as good as expected, and several
      modifications to the original technique have been proposed. Long-term
      effectiveness studies comparing different techniques of antireflux surgery are
      limited. Our group developed a new concept in antireflux surgery (complete fixed
      "nondeformable" fundoplication) in order to improve its outcome; we present the
      long-term comparative results of this novel concept/technique. METHODS: Overall,
      512 patients were included in the study and assigned into 1 of 3 fundoplications
      groups: partial (131), Nissen (133), and fixed "nondeformable" (121). We compared
      the groups with each other and with a group who chose to receive medical
      treatment (MT) (127). All patients underwent clinical evaluation, upper
      gastrointestinal endoscopy, esophageal manometry, 24-hour esophageal pH
      monitoring, and the SF-36 health status survey prior to operation and at 1, 5,
      10, and 15 years of follow-up. RESULTS: At the 15-year follow-up, we were able to
      complete the protocol in 319 patients: 103 patients from the partial group, 102
      patients from the Nissen group, 97 patients from the fixed "nondeformable" group,
      and 17 patients from the medical treatment group. A lower prevalence of erosive
      gastroesophageal reflux disease (GERD) was observed in the fixed "nondeformable"
      group (7.20%) versus 21.56% for Nissen, 39.80% for partial, and 47.05% for MT (P
      < .01). Lower esophageal sphincter (LES) pressure and LES length were more
      constant in the fixed "nondeformable" group (14.7 mm Hg/2.2 cm) compared with the
      Nissen (9 mm Hg/0.7 cm), partial (7 mm Hg/2 cm), and MT (5.64 mm Hg/1.3 cm)
      groups (P < .01). Reflux recurrence was observed in 168 patients (13 in fixed
      "nondeformable," 41 in Nissen, and 98 in partial (P < .01). CONCLUSION: The
      complete fixed "nondeformable" fundoplication showed best results in studied
      parameters and had a lower long-term recurrence compared with Nissen and partial
      techniques.

PMID- 21943635
TI  - Living donor liver transplantation for recurrent hepatocellular carcinoma after
      liver resection.
AB  - BACKGROUND: Little is known about outcomes and indications for living donor liver
      transplantation in patients with recurrent hepatocellular carcinoma after liver
      resection. METHODS: We analyzed retrospectively 176 patients with hepatocellular
      carcinoma who underwent living donor liver transplantation at our institute
      between February 1999 and December 2009. Among 128 of 176 patients with a history
      of pretreatment for hepatocellular carcinoma, 19 patients underwent radical liver
      resection. We compared patient characteristics, intraoperative blood loss,
      operative duration, and long-term outcomes including overall survival and
      recurrence rates between patients who had received hepatectomy, other
      pretreatments, and no pretreatments. RESULTS: The surgical duration was
      significantly longer in patients with pretransplant hepatectomy than in those who
      had undergone other types of pretreatment (n = 109) or none (n = 48), whereas
      intraoperative blood loss did not differ among the 3 groups. Overall survival and
      recurrence rates did not significantly differ among the 3 groups. In patients
      with pretransplant hepatectomy, survival rates were significantly higher among
      patients who met the Kyoto criteria (<=10 tumors, all <=5 cm in diameter and
      serum des-gamma-carboxy prothrombin levels <=400 mAU/mL; n = 15) than those with
      values that exceeded the Kyoto criteria (n = 4) (5-year survival rates, 93% vs
      25%, P = .005). Similarly, recurrence rates were significantly lower among
      patients meeting than exceeding the Kyoto criteria (5-year recurrence rates, 10%
      vs 67%, P = .011). CONCLUSION: Patients with hepatocellular carcinoma recurrence
      after liver resection can safely undergo living donor liver transplantation. Long
      term outcomes can be particularly favorable in patients who meet the Kyoto
      criteria.

PMID- 21943636
TI  - Mechanisms of glucose uptake in intestinal cell lines: role of GLUT2.
AB  - BACKGROUND: GLUT2 is translocated to the apical membrane of enterocytes exposed
      to glucose concentrations >~50 mM. Mechanisms of GLUT2-mediated glucose uptake in
      cell culture models of enterocytes have not been studied. AIM: To explore
      mechanism(s) of glucose uptake in 3 enterocyte-like cell lines. METHODS: Glucose
      uptake was measured in Caco-2, RIE-1, and IEC-6 cell lines using varying
      concentrations of glucose (0.5-50 mM). Effects of phlorizin (SGLT1 inhibitor),
      phloretin (GLUT2 inhibitor), nocodazole and cytochalasin B (disrupters of
      cytoskeleton), calphostin C and chelerythrine (PKC inhibitors), and phorbol 12
      myristate 13-acetate (PKC activator) were evaluated. RESULTS: Phlorizin inhibited
      glucose uptake in all 3 cell lines. Phloretin inhibited glucose uptake in Caco-2
      and RIE-1 cells. Starving cells decreased glucose uptake in Caco-2 and RIE-1
      cells. Glucose uptake was saturated at >10 mM glucose in all 3 cell lines when
      exposed briefly (<1 min) to glucose. After exposure for >5 min in Caco-2 and RIE
      1 cells, glucose uptake did not saturate and K(m) and V(max) increased. This
      increase in glucose uptake was inhibited by phloretin, nocodazole, cytochalasin
      B, calphostin C, and chelerythrine. PMA enhanced glucose uptake by 20%.
      Inhibitors and PMA had little or no effect in the IEC-6 cells. CONCLUSION:
      Constitutive expression of GLUT2 in the apical membrane along with additional
      translocation of cytoplasmic GLUT2 to the apical membrane via an intact
      cytoskeleton and activated PKC appears responsible for enhanced carrier-mediated
      glucose uptake at greater glucose concentrations (>20 mM) in Caco-2 and RIE-1
      cells. IEC-6 cells do not appear to express functional GLUT2.

PMID- 21943637
TI  - Components separation for abdominal wall reconstruction: the Memphis
      modification.
AB  - Since the advent of damage control surgery, more patients are left with an open
      abdomen. Surgeons are then left with the challenge of how to restore continuity
      of the abdominal wall. Many different techniques have been utilized for
      reconstruction with widely variable recurrence rates, mainly depending on the
      length of follow-up. A modification of the components separation technique was
      developed in Memphis, Tennessee at the Presley Memorial Trauma Center. This
      modification greatly increased the length gained in the midline. Additionally,
      many patients can be reconstructed without the use of prosthetics, reducing the
      infectious complications. The purpose of this manuscript is to describe in detail
      how to perform a modification of the components separation technique that has
      been shown to have one of the lowest recurrence rates in the literature.

PMID- 21943638
TI  - Elective living donor liver transplantation by hybrid hand-assisted laparoscopic
      surgery and short upper midline laparotomy.
AB  - BACKGROUND: Although the technique of liver transplantation is well developed,
      the invasiveness of the operation can be decreased with laparoscopic procedures.
      METHODS: We performed elective living donor liver transplantation (LDLT) through
      a short midline incision combined with hand-assisted laparoscopic surgery (HALS).
      Nine selected patients with end stage liver disease underwent the procedure
      between July, 2010 and February, 2011 (median age 60, median Child-Pugh 9, median
      MELD score 14). Splenectomy was performed simultaneously in 7 cases. The liver
      (and spleen) were mobilized by a sealing device under a HALS procedure with an 8
      cm upper midline incision, followed by explantation of the diseased liver (and
      spleen) through the upper midline incision which was extended to 12 to 15 cm.
      Partial liver grafts were implanted through the upper midline incision. RESULTS:
      The median duration of the operation was 741 minutes, the median time needed for
      anastomosis was 48 minutes, the median blood loss was 3,940 g, and the median
      liver weight was 866 g. Eight recipients are alive and have good graft function.
      A difficult implantation for one patient required an additional right transverse
      incision. When compared with 13 recent liver recipients who underwent LDLT with a
      regular Mercedes-Benz-type incision, no clinically relevant drawbacks of the HALS
      hybrid procedure were observed. CONCLUSION: We have shown the feasibility and
      safety of LDLT performed through a short midline incision without abdominal
      muscle disruption with the aid of HALS.

PMID- 21943639
TI  - Induction of regulatory T cells and prolongation of survival of fully allogeneic
      cardiac grafts by administration of Tokishakuyaku-san in mice.
AB  - BACKGROUND: The Japanese herbal medicine Tokishakuyaku-san (TJ-23) has been used
      to treat neurodegenerative, immune, and respiratory tract diseases, as well as
      many gynecologic disorders, with few adverse effects. This study investigated the
      effect of TJ-23 on alloimmune responses in a murine model of cardiac allograft
      transplantation. METHODS: CBA mice underwent transplantation of a C57BL/6 heart
      and received oral administration of 2 g/kg per day of TJ-23 or 1 of 16 other
      commonly used Japanese herbal medicines from the day of transplantation until 7
      days afterward. An adoptive transfer study was conducted to determine whether
      regulatory cells were generated. Histologic and cell proliferation studies,
      cytokine measurements, and flow cytometry analyses were also performed. RESULTS:
      Of the 17 herbal medicines studied, only TJ-23, given in a dose of 2 g/kg per
      day, induced significantly prolonged allograft survival (median survival time
      [MST], >100 days). TJ-23 also suppressed proliferation of splenocytes and
      production of interleukin-2, interleukin-6, and interferon-gamma. Adoptive
      transfer of either whole splenocytes or CD4(+) or CD4(+) CD25(+) cells from TJ-23
      treated allograft recipients resulted in indefinite survival of allografts in
      naive secondary recipients (MST >100 days). Flow cytometry studies showed that
      the CD4(+) CD25(+) forkhead/winged-helix (FOXP3)(+) regulatory cell population
      was increased in transplant recipients given TJ-23. CONCLUSION: TJ-23 induced
      hyporesponsiveness to fully allogeneic cardiac allografts and generated CD4(+)
      CD25(+) regulatory cells in our model.

PMID- 21943640
TI  - Carotid endarterectomy protects elderly patients from cognitive decline: a
      prospective study.
AB  - BACKGROUND: Carotid endarterectomy (CEA) reduces the risk of stroke in selected
      patients with symptomatic and asymptomatic carotid disease, but its beneficial
      influence on cognitive performance in the elderly remains debatable. This
      prospective study sought to determine early and long-term neurocognitive outcomes
      after CEA for severe unilateral carotid artery stenosis. METHODS: From July 2006
      to December 2008, 75 symptomatic (group A) and 70 asymptomatic patients (group B)
      aged 65 years and older underwent CEA under general anesthesia. Sixty-eight age-
      and sex-matched individuals who underwent laparoscopic cholecystectomy during the
      same period at our institution served as a control group (group H). Patients with
      contralateral severe carotid stenosis or occlusion and those with dementia,
      depression, or a history of major stroke were excluded. Cognitive function was
      assessed using 2 neuropsychological tests (the Mini-Mental State Examination
      [MMSE] and the Montreal Cognitive Assessment [MoCA]) performed preoperatively
      (T0) and then 3 (T1) and 12 months (T2) after operation. A change of at least 2
      points between the scores at T0 and T2 was arbitrarily considered as clinically
      significant. RESULTS: At T0, group A revealed significant cognitive impairments
      in both mean test scores by comparison with group H (P = .005 and P < .01,
      respectively), whereas there were no significant differences between groups A and
      B, or between groups B and H. Postoperatively, symptomatic patients had
      significant improvements in their mean cognitive performance scores in both tests
      (P < .01 and P < .01, respectively), whereas there were no changes in the
      asymptomatic and control patients' scores. No significant differences emerged for
      the MMSE scores in the 3 groups, whereas there was a marginally significant
      difference in the MoCA scores between groups A and H (P = .08), but not for A
      versus B or B versus H when clinically significant scores were considered.
      CONCLUSION: Our study showed that only elderly symptomatic patients with severe
      carotid lesions had a significant improvement in cognitive performance scores
      after CEA, although the benefit was considered clinically not significant. This
      suggests that CEA does not diminish neurocognitive functions, but it might
      provide some protection against cognitive decline in the elderly.

PMID- 21943642
TI  - Sirolimus drug-eluting, hydrogel-impregnated polypropylene mesh reduces intra
      abdominal adhesion formation in a mouse model.
AB  - BACKGROUND: Prosthetic mesh is used frequently in abdominal wall hernia
      reconstruction but is prone to postoperative adhesion formation. Complications
      resulting from intra-abdominal adhesions represent a considerable clinical and
      cost burden. We, herein, investigate the antiproliferative and antiadhesiogenic
      properties of sirolimus and hydrogel-impregnated, drug-eluting mesh to decrease
      such complications in a mouse model of abdominal wall hernia repair. METHODS: A 1
      * 1cm(2) polypropylene mesh from 1 of 3 groups (group 1, plain control; group 2,
      hydrogel [2% agarose]; and group 3, hydrogel + 10 mcg sirolimus) was implanted
      operatively into the peritoneal cavity of BALB/c mice and followed for up to 4
      weeks. Adhesions were scored by percent surface area of mesh (range, 0-100%),
      severity (range, 0-3), and tenacity (range, 0-4). Representative samples were
      assessed by scanning electron microscopy. RESULTS: Mesh impregnated with the
      combination of hydrogel and sirolimus led to a significant decrease in adhesion
      formation. The percent surface area of adhesional attachment to mesh was
      decreased from 100.0 +/- 0% in the plain mesh control group versus 18 +/- 8% (P <
      .001) in the combined impregnated mesh group. Similarly, adhesion severity scores
      were decreased from a score of 2.9 +/- 0.1 (plain mesh) versus 1.4 +/- 0.1
      (sirolimus/hydrogel-impregnated mesh) (P < .001). Scores for tenacity were also
      decreased markedly from 3.5 +/- 0.2 (plain mesh) versus 1.5 +/- 0.1
      (sirolimus/hydrogel-impregnated mesh (P < .001). CONCLUSION: Creation of a
      sirolimus drug-eluting and hydrogel-impregnated polypropylene mesh resulted in
      marked decrease of adhesion formation in this mouse model, was well tolerated
      without side effects, and has potential for clinical application.

PMID- 21943643
TI  - Mesh hernia repair and male infertility: a retrospective register study.
AB  - BACKGROUND: Previous studies have suggested that the use of mesh in groin hernia
      repair may be associated with an increased risk for male infertility as a result
      of inflammatory obliteration of structures in the spermatic cord. In a recent
      study, we could not find an increased incidence of involuntary childlessness. The
      aim of this study was to evaluate this issue further. METHODS: Men born between
      1950 and 1989, with a hernia repair registered in the Swedish Hernia Register
      between 1992 and 2007 were cross-linked with all men in the same age group with
      the diagnosis of male infertility according to the Swedish National Patient
      Register. The cumulative and expected incidences of infertility were analyzed.
      Separate multivariate logistic analyses, adjusted for age and years elapsed since
      the first repair, were performed for men with unilateral and bilateral repair,
      respectively. RESULTS: Overall, 34,267 men were identified with a history of at
      least 1 inguinal hernia repair. A total of 233 (0.7%) of these had been given the
      diagnosis of male infertility after their first operation. We did not find any
      differences between expected and observed cumulative incidences of infertility in
      men operated with hernia repair. Men with bilateral hernia repair had a slightly
      increased risk for infertility when mesh was used on either side. However, the
      cumulative incidence was less than 1%. CONCLUSION: Inguinal hernia repair with
      mesh is not associated with an increased incidence of, or clinically important
      risk for, male infertility.

PMID- 21943641
TI  - Human ghrelin protects animals from renal ischemia-reperfusion injury through the
      vagus nerve.
AB  - BACKGROUND: Acute kidney injury secondary to renal ischemia and reperfusion
      injury is widely prevalent. Ghrelin, which is a stomach-derived peptide, has been
      shown to be anti-inflammatory. The purpose of this study was to examine whether
      human ghrelin has any beneficial effects after renal ischemia and reperfusion
      injury, and if so, whether ghrelin's action in renal ischemia and reperfusion
      injury is mediated by the vagus nerve. METHODS: Male adult rats were subjected to
      renal ischemia and reperfusion by bilateral renal pedicle clamping for 60 min,
      treated intravenously with human ghrelin (4 nmol/rat) or normal saline (vehicle)
      immediately after reperfusion. After 24 h, the animals were killed and samples
      were harvested. In separate groups, subdiaphragmatic vagotomy prior to renal
      ischemia and reperfusion was performed, treated with human ghrelin or vehicle,
      and at 24 h, blood and organs were harvested. RESULTS: Renal ischemia and
      reperfusion injury caused significant increases in the serum levels of tissue
      injury markers compared with the sham operation. Human ghrelin treatment
      attenuated serum creatinine and blood urea nitrogen significantly by 55% and 53%,
      and liver enzymes (aminotransferase [AST] and alanine aminotransferase [ALT]) by
      20% and 24%, respectively, compared with the vehicle-treated groups. Tissue water
      contents, plasma and kidney interleukin-6, and kidney myeloperoxidase activity
      were decreased. Bcl-2/Bax ratio was increased, and histology of the kidneys was
      improved. More importantly, prior vagotomy abolished ghrelin's protective effect
      in tissue injury markers and tissue water contents in renal ischemia and
      reperfusion injured animals. CONCLUSION: Human ghrelin treatment in renal
      ischemia and reperfusion injured rats attenuated systemic and kidney-specific
      inflammatory responses. The protection of human ghrelin in renal ischemia and
      reperfusion injury was mediated by the vagus nerve. These data suggest that
      ghrelin can be developed as a novel treatment for patients with acute kidney
      injury induced by renal ischemia and reperfusion injury.

PMID- 21943644
TI  - Toxicity of mixtures of perfluorooctane sulphonic acid with chlorinated chemicals
      and lipid regulators.
AB  - The toxicological interaction of perfluorooctane sulphonic acid (PFOS) with the
      chlorinated pollutants triclosan and 2,4,6-trichlorophenol and the lipid
      regulators gemfibrozil and bezafibrate was evaluated using the combination index
      isobologram equation. The endpoint for bioassays was the growth rate inhibition
      of the green alga Pseudokirchneriella subcapitata. The results showed that most
      of the binary combinations assayed exhibited antagonism at all effect levels. The
      addition of a third component induced a less antagonistic or even synergistic
      behaviour. This was particularly marked for the ternary mixture of triclosan and
      2,4,6-trichlorophenol with PFOS, for which synergism was very strong at all
      effect levels, with a combination index as low as 0.034 +/- 0.002 at EC(50) for
      the mixture. The results obtained indicate that the evaluation of mixture
      toxicity from single component data using the concentration addition approach
      could severely underestimate combined toxicity.

PMID- 21943645
TI  - Interference by the activated sludge matrix on the analysis of soluble microbial
      products in wastewater.
AB  - The objective of this study was to demonstrate the effects of complex matrix
      effects caused by chemical materials on the analysis of key soluble microbial
      products (SMP) including proteins, humics, carbohydrates, and polysaccharides in
      activated sludge samples. Emphasis was placed on comparison of the commonly used
      standard curve technique with standard addition (SA), a technique that differs in
      that the analytical responses are measured for sample solutions spiked with known
      quantities of analytes. The results showed that using SA provided a great
      improvement in compensating for SMP recovery and thus improving measurement
      accuracy by correcting for matrix effects. Analyte recovery was found to be
      highly dependent on sample dilution, and changed due to extraction techniques,
      storage conditions and sample composition. Storage of sample extracts by freezing
      changed SMP concentrations dramatically, as did storage at 4 degrees C for as
      little as 1d.

PMID- 21943646
TI  - Plasma membrane cholesterol plays a critical role in the Salmonella-induced anti
      inflammatory response in intestinal epithelial cells.
AB  - Our recent study demonstrated that a phosphatidylinositol-3 kinase (PI3K)/Akt
      dependent anti-inflammatory pathway was activated by Salmonella in intestinal
      epithelial cells. Salmonella virulence is dependent on the ability of the
      bacterium to invade nonphagocytic host cells and then survive and replicate
      within modified Salmonella-containing vacuoles where cholesterol accumulates. In
      addition, cholesterol in membrane lipid rafts is frequently a platform for the
      activation of downstream signaling pathways, including the PI3K/Akt pathway.
      However, the role of plasma membrane cholesterol in the Salmonella-induced anti
      inflammatory response in intestinal epithelial cells has not been elucidated.
      Here, we show that the effect of plasma membrane cholesterol depletion on the
      inhibition of Akt activation allows sustained ERK activation and the subsequent
      upregulation of IL-8 expression. These results demonstrate that plasma membrane
      cholesterol plays a critical role in the PI3K-dependent anti-inflammatory pathway
      activated by Salmonella in intestinal epithelial cells.

PMID- 21943647
TI  - Choice of resident costimulatory molecule can influence cell fate in human naive
      CD4+ T cell differentiation.
AB  - With antigen stimulation, naive CD4+ T cells differentiate to several effector or
      memory cell populations, and cytokines contribute to differentiation outcome.
      Several proteins on these cells receive costimulatory signals, but a systematic
      comparison of their differential effects on naive T cell differentiation has not
      been conducted. Two costimulatory proteins, CD28 and ICAM-1, resident on human
      naive CD4+ T cells were compared for participation in differentiation. Under
      controlled conditions, and with no added cytokines, costimulation through either
      CD3+CD28 or CD3+CAM-1 induced differentiation to T effector and T memory cells.
      In contrast, costimulation through CD3+ICAM-1 induced differentiation to Treg
      cells whereas costimulation through CD3+CD28 did not.

PMID- 21943649
TI  - Association of socioeconomic position with under- and overnutrition in Pakistan.
AB  - OBJECTIVE: We assessed the relationship between socioeconomic position (SEP) and
      under- and overnutrition in Pakistani adults. METHODS: In 2006, we conducted a
      cross-sectional study including adult participants >=20 years of age (n = 3500)
      residing in district Khairpur in Sindh province of Pakistan. We categorized body
      mass index (BMI) into <18.5 (underweight), 18.6-22.5 (normal BMI), 23-24.9
      (preoverweight), 25-29.9 (overweight), and >=30 (obese). We assessed the
      association of SEP based on wealth index measured as quintiles of a linear index
      derived from household assets and utilities score with categories of BMI through
      multinomial regression with the use of normal BMI as reference category while
      accounting for sampling design. RESULTS: After adjusting for age, sex, education
      level, and occupation, there was no significant association of SEP and
      underweight, whereas SEP was positively associated with the categories of
      preoverweight, overweight, and obesity. In comparison with the 1st quintile,
      those in upper wealth quintiles had significantly greater odds of being
      preoverweight (4th quintile: adjusted odds ratio [adjOR], 1.47; 95% confidence
      interval [95% CI], 1.04-2.08; 5th quintile: adjOR, 1.57; 95% CI, 1.12-2.21),
      overweight (4th quintile; adjOR, 1.97; 95% CI, 1.43-2.72; 5th quintile: adjOR,
      2.66; 95% CI, 1.91-3.69) and obese (4th quintile: adjOR, 2.24; 95% CI, 1.37-3.69;
      5th quintile: adjOR, 3.65; 95% CI, 2.14-6.22). CONCLUSION: Shift from under- to
      overnutrition across SEP groups is occurring in Pakistan. There is a need for re
      evaluating national policies and programs to tackle the growing burden of
      emerging over-nutrition along with rampant under-nutrition.

PMID- 21943648
TI  - Yard flooding by irrigation canals increased the risk of West Nile disease in El
      Paso, Texas.
AB  - PURPOSE: To investigate the effects of use of water from irrigation canals to
      flood residential yards on the risk of West Nile disease in El Paso, Texas.
      METHODS: West Nile disease confirmed cases in 2009 through 2010 were compared
      with a random sample of 50 residents of the county according to access to and use
      of water from irrigation canals by subjects or their neighbors, as well as geo
      referenced closest distance between their home address and the nearest irrigation
      canal. A windshield survey of 600 m around the study subjects' home address
      recorded the presence of irrigation canals. The distance from the residence of
      182 confirmed cases of West Nile disease reported in 2003 through 2010 to canals
      was compared with that of the centroids of 182 blocks selected at random.
      RESULTS: Cases were more likely than controls to report their neighbors flooded
      their yards with water from canals. Irrigation canals were more often observed in
      neighborhoods of cases than of controls. Using the set of addresses of 182
      confirmed cases and 182 hypothetical controls the authors found a significant,
      inverse relation with risk of West Nile disease. CONCLUSIONS: Flooding of yards
      with water from canals increased the risk of West Nile disease.

PMID- 21943650
TI  - Chest and neck mobilization effects on spirometric responses in healthy subjects.
AB  - OBJECTIVES: In this observational study, we evaluated the effects of chest and
      neck mobilization on spirometric parameters in healthy subjects. METHODS: We
      conducted an observational, quantitative, and experimental study in a sample of
      100 healthy subjects. We evaluated spirometric parameters before and after
      pompage mobilization techniques. Three techniques were used, and each technique
      was performed 6 times. RESULTS: Forced vital capacity (3.4 +/- 0.1 L vs 3.5 +/-
      0.1 L), forced expiratory volume at the first second (3.2 +/- 0.09 L vs 3.3 +/-
      0.09 L), and peak expiratory flow (6.4 +/- 0.27 L/s vs 6.6 +/- 0.25 L/s) were
      significantly increased after mobilization (P < .0001), whereas Tiffeneau index
      (94% +/- 1% vs 6% +/- 0.2%) was decreased (P < .0001). CONCLUSION: Chest and neck
      mobilization techniques used in this study improved spirometric parameters in a
      group of young and healthy subjects.

PMID- 21943651
TI  - Immunization status of adult chiropractic patients in analyses of national health
      interview survey.
AB  - OBJECTIVE: Two recent studies that examined National Health Interview Survey data
      reported divergent findings regarding the propensity of adult chiropractic users
      to receive seasonal influenza immunization. Although one study found a
      statistically significant negative association between chiropractic use and
      influenza vaccination, another found that chiropractic users were significantly
      more likely to be vaccinated. The purpose of this study is to extend previous
      works by delving more deeply into recent data to identify adult chiropractic
      users at high risk and high priority for vaccination against influenza and
      pneumococcal disease. METHODS: We used data from the 2007 National Health
      Interview Survey in an attempt to replicate previous methodologies and further
      examine vaccination among adult chiropractic users (age >=18 years) who,
      according to the Center for Disease Control and Prevention guidelines, should
      receive influenza and/or pneumococcal vaccination. We used complex survey design
      methods to make national estimates and used logistic regression to determine if
      having used chiropractic care predicted vaccination. RESULTS: We found major
      methodological differences between the prior studies. In our analyses, we found
      that chiropractic users were significantly less likely than nonusers to have
      received the pneumococcal vaccine, and we found no significant difference between
      chiropractic users and nonusers relative to having received the seasonal flu
      vaccine. CONCLUSIONS: Methodological differences in previous studies that
      investigated the association between chiropractic care and adult vaccination
      likely explain divergent findings reported in the literature. Future studies
      should consider these differences.

PMID- 21943652
TI  - Timeliness of lung cancer diagnosis and treatment in a rapid outpatient
      diagnostic program with combined 18FDG-PET and contrast enhanced CT scanning.
AB  - INTRODUCTION: Delays in the diagnosis of lung cancer are under debate and may
      affect outcome. The objectives of this study were to compare various delays in a
      rapid outpatient diagnostic program (RODP) for suspected lung cancer patients
      with those described in literature and with guideline recommendations, to
      investigate the effects of referral route and symptoms on delays, and to
      establish whether delays were related to disease stage and outcome. METHODS: A
      retrospective chart study was conducted of all patients with suspected lung
      cancer, referred to the RODP of our tertiary care university clinic between 1999
      and 2009. Patient characteristics, tumor stage and different delays were
      analyzed. RESULTS: Medical charts of 565 patients were retrieved. 290 patients
      (51.3%) were diagnosed with lung cancer, 48 (8.5%) with another type of
      malignancy, and in 111 patients (19.6%) the radiological anomaly was diagnosed as
      non-malignant. In 112 (19.8%) no immediate definite diagnosis was obtained,
      however in 82 of these cases (73.2%) the proposed follow-up strategy confirmed a
      benign outcome. The median first line delay was 54 days, IQR (interquartile
      range) 20-104 days, median patient delay 19 days (IQR 4-52 days), median referral
      delay was 7 days (IQR 5-9 days), median diagnostic delay 2 days (IQR 1-19 days).
      In 87% a diagnosis was obtained within 3 weeks after visiting a chest physician
      and 52.5% started curative therapy within 2 weeks after diagnosis. Patients
      presenting with hemoptysis had shorter first line delays. The RODP care was
      generally far more timely compared to literature and published guidelines, except
      for both referral and palliative therapeutic delay. No specific delay was
      significantly related to disease stage or survival. CONCLUSIONS: An RODP results
      in a timely diagnosis well within guideline recommendations. Patient and first
      line delay account for most of total patient delay. Within the limitations of
      this retrospective study, we found no association with disease stage or survival.

PMID- 21943653
TI  - [Rectourethral fistulae: diagnosis and management. Review of the literature].
AB  - INTRODUCTION: Rectourethral fistulae are predominantly of iatrogenous origin.
      They alter the patient's quality of life and are difficult to manage from a
      medical standpoint. PATIENTS AND METHODS: The major series of patients of the
      last 20 years have been analyzed, in order to define the best management of
      rectourethral fistulae. RESULTS: Many surgical techniques have been tried, as
      well as several protocols, ranging from simple urinary and fecal diversion to
      diversion followed by reconstruction and regional flap in case of tissue damage.
      CONCLUSION: The fistula's cause and the use of radiotherapy had a major impact on
      its prognosis. The best-suited protocol was the 3-step protocol, which has been
      described within. The flap, which seemed to have the best results, was the
      gracilis muscle flap.

PMID- 21943654
TI  - [Sipuleucel-T: a prostate cancer vaccine: "instructions for use" for urologists].
AB  - Sipuleucel-T is the first approved vaccine for prostate cancer, opening the
      pathway for this new treatment approach. The treatment process consists in
      isolating the patient dentritic cells via leukapherisis, stimulate and infuse
      them into the patient. These enhanced cells are then able to stimulate patient T
      lymphocytes to target the tumour cells. The median survival in the pivotal study,
      IMPACT, as well as in the previously reported randomised trials, was 4.1 months
      longer in the sipuleucel-T group. The estimated probability of survival 36 months
      after randomisation was 31.7% in the sipuleucel-T group and 23.0% in the placebo
      group. However, the median time to objective disease progression was similar in
      the two groups (hazard ratio: 0.95; 95% CI, 0.77 to 1.17; P=0.63). We report
      herein, the treatment modalities, side effects and results in the light of
      recently published randomised trials.

PMID- 21943655
TI  - [Imperative partial nephrectomy for renal cell carcinoma: oncological and
      functional results].
AB  - OBJECTIVES: To study oncological results and functional results after partial
      nephrectomy in imperative indication for the treatment of renal cell carcinoma.
      PATIENTS AND METHODS: From January 1990 to December 2009, 65 partial
      nephrectomies in 61 patients were performed in imperative indication for renal
      cell carcinoma. RESULTS: The mean age of patients was 59.3 years. The mean follow
      up was 47.4 months. The tumours were asymptomatic in 87.5%. The average tumour
      diameter was 4.3 cm. Twenty-nine percent of patients relapsed after a mean time
      of 27.4 months. The morbidity was 38.5%. Preoperative and endpoint serum
      creatinine and renal clearance were respectively 119 MUmol/L and 63.1 mL/min
      versus 137 MUmol/L and 50.9 mL/min (P=0.0003; 0.0002). Overall survival at one,
      three, five and ten years was 98.4%, 91.2%, 91.2% and 51.9%. CONCLUSION: Partial
      nephrectomy in imperative indication for renal cell carcinoma has helped preserve
      renal function but has a significant morbidity and recurrence rate.

PMID- 21943656
TI  - [Carcinological results of laparoscopic adrenalectomy for adrenal metastasis].
AB  - INTRODUCTION AND OBJECTIVES: Indication of laparoscopic adrenalectomy for adrenal
      metastasis remains debated. Our aim was to analyze its carcinological results.
      MATERIAL AND METHODS: In a series of 332 laparoscopic adrenalectomies, 13 were
      for adrenal metastasis (kidney=5, lung=3, melanoma=3, breast=1, eye=1). The
      indication was curative (single metastasis) in nine cases (69%), the four other
      patients (31%) having a polymetastatic disease. All alive patients were
      interviewed in August 2010. Survival was estimated using the Kaplan-Meyer method,
      with comparisons using the log rank test. RESULTS: Mean operative time was 174.2
      +/- 102 minutes. Blood loss was 351 +/- 136 mL. Three conversions (23%) were
      necessary, for gastric perforation, wound of vena cava and inability to dissect
      the adrenal. Surgical margins were positive in six cases (46%). The risk of
      positive margin was lower in case of metastasis of renal cell carcinoma (Fischer,
      p=0.02). The median of overall survival was 14 months (3-45). Survival was
      significantly higher in metastases of renal cell carcinoma (p=0.035) than in
      metastases of other tumors, 24 months (11-36) vs six months (3-45), respectively.
      There was no difference according to the laparoscopic technique used, neither
      according to the age, nor according to the tumoral size. CONCLUSIONS:
      Laparoscopic surgery did not offer sufficient guarantee to be considered as the
      standard treatment in case of adrenal metastasis. However, with a survival rate
      of 60%, a lower rate of surgical margins, metastases of renal cell carcinoma seem
      to be the better candidates for laparoscopic adrenalectomy.

PMID- 21943657
TI  - [Prostate cancer: Gleason scores correlation between biopsies and surgical gross
      specimen].
AB  - The Gleason score is a histopronostic criterion which gives an appraisal of
      prostate cancer aggressiveness and outcomes. OBJECTIVE: The goal of this
      retrospective study was to assess the relationship between Gleason scores
      appreciated on biopsies and later on surgical gross specimen. RESULTS: During the
      period of the study, 123 patients benefit of a histological diagnosis of prostate
      cancer recording Gleason score on biopsies and postsurgical intervention on gross
      specimen. After analysis of biopsies and for gross specimen the reported Gleason
      scores vary from 3 to 9 and the mean was 5.9 and 6.1 respectively. There was a
      good concordance between the Gleason scores for biopsies and gross specimen in
      about 32.5% of cases. We noted a difference of score of one point in 37.3% of
      patients and a difference of two points and more in 30% of cases. In 28.4% the
      Gleason scores were overestimated while in 39% they were underestimated. More
      than half of the patients' cohort was classified in the group of histologically
      moderately differentiated cancer. When grouping the patients according to the
      histological types well, moderately or less differentiated cancers, the Gleason
      scores concordance for biopsies and for gross specimen change from 32.5% up to
      74.8%. The correlation can be considered good for the less differentiated
      cancers. CONCLUSION: Gleason score showed some limits in the appreciation of the
      prediction. The grouping of patients according to the three distinct histological
      differentiation groups increases the concordance between the score of Gleason on
      biopsy specimen and gross specimen but it seems less powerful for cancers well
      and moderately differentiated cancers.

PMID- 21943658
TI  - [HIFU for prostate cancer in patients with a history of severe colorectal
      disease].
AB  - OBJECTIVES: To report the functional and oncological outcomes of HIFU for
      prostate cancer in patients with a history of severe colorectal disease. METHODS:
      Between 2002 and 2009, 14 patients with a history of severe colorectal disease
      (cancer, lymphoma, inflammatory bowel diseases [IBD]) were treated with HIFU as a
      primary care option for localized prostate cancer. RESULTS: Mean age was 65.8 +/-
      6.1 years. Mean time between colorectal disease treatment and HIFU was 10.6 +/-
      6.8 years. The mean Prostate Specific Antigen (PSA) before HIFU was 12.1 ng/mL
      (4.5-55). Gleason score was inferior or equal to 6 in four patients (28.6%),
      equal to 7 in nine patients (64.3%) and superior or equal to 8 in one patient
      (7.1%). The mean prostate volume before HIFU was 22.1 +/- 11.7 mL. The number of
      HIFU sessions per patient was 1.35. The mean nadir PSA was 0.61 +/- 0.82 ng/mL.
      Systematic control biopsies were negative in seven patients (50%). Mean follow-up
      was 22 months with a 35.7% complication rate (three erectile dysfunctions, two
      urinary stress incontinences). No recto-urethral fistula occurred. CONCLUSION:
      HIFU was an interesting therapy for patients with a history of colorectal disease
      for whom regular treatment was challenging or non feasible.

PMID- 21943659
TI  - [Male stress urinary incontinence: medium-term results of treatment by sub
      urethral bone anchored sling InVanceTM].
AB  - OBJECTIVE: To analyze the functional and urodynamic results of a compressive sub
      urethral sling with bone anchoring InVanceTM. METHODS: One hundred and six
      successive patients were operated with this system between August 2004 and March
      2009. Urinary incontinence was classified according to the number of daily
      protections. All the patients have benefited from a clinical, endoscopic and
      urodynamic pre and post-operative evaluation. The results were classified in four
      groups, at three months and at one year, according to whether the patients were
      dry (A), very improved (B), little improved (C), or with no improvement (D).
      RESULTS: The average age of the patients during the installation of the strip was
      67.4 years (46-82). At three months, the rate of dry (A) or very improved
      patients (B) was of 81.2% (A=75.5%; B=5.7%), and at one year: 75.5% (A=61%;
      B=14.5%). At three months, the rate of patients little improved (C) or not
      improved (D) was of 18.8% (C=16%; D=2.8%), and at one year: 24.5% (C=20.3%;
      D=4.2%). These results deteriorated according to the initial rank of incontinence
      II, III, and I. Six patients (5.7%) were explanted because of a prosthetic
      infection which perished at an average of 9 months (3-18). Infection was linked
      to operative time (p=0.02), and patients age. No osteitis nor urethral erosion
      were noted. There was a significant rise in the pressures of maximum fence at
      rest and maximum urethral pressures in reserve (p=0.01). At one year, score ICIQ
      UI SF decreased overall by 7.1 points. CONCLUSION: The medium-term results of
      under-urethral supporting with bone anchoring InVanceTM are very encouraging.
      This technique presents an acceptable morbidity and a good tolerance. It can be
      proposed in first intention for a urinary incontinence whatever the rank is, even
      if the effectiveness is particularly present in incontinences of rank I and II.

PMID- 21943660
TI  - [De novo stress urinary incontinence following sacral colpopexy].
AB  - OBJECTIVE: To evaluate the risk of occurrence of de novo stress urinary
      incontinence (SUI) after sacral colpopexy (SCP). PATIENTS AND METHODS: In all, 57
      women with no concomitant or occult SUI, had a SCP for urogenital prolapse
      between January 2006 and October 2009. Some data from their medical charts (age,
      body mass index, past medical history, maximum urethral closure pressure, bladder
      neck hypermobility) were reviewed retrospectively and statistically analyzed to
      assess the association between these factors and de novo SUI. RESULTS: With a
      median follow-up of 16 months, four patients (7.3%) developed de novo SUI 1 year
      postoperative and which required the wearing of pads defensively, three of which
      were significantly improved after pelviperineal rehabilitation, however only one
      patient: 1.8% required the establishment of a sub-urethral tape 8 months after
      the surgical correction of prolapse. No statistically significant association has
      been established despite a P<0.01 between the sphincter deficiency (SD) and de
      novo SUI because of a sample too small inferior to five, however predictive
      values for PPV and NPV, the MUCP was 43 and 2.2%. CONCLUSION: The results of this
      study were consistent with the literature data, the risk to our patients to
      develop de novo SUI requiring secondly anti-incontinence procedure was lower:
      7.3% but could become more important: 43% if preoperative SD. Patients should
      always be informed before surgery as it cannot be predicted.

PMID- 21943661
TI  - [Does the urologist in formation have a burnout syndrome? Evaluation by Maslach
      Burnout Inventory (MBI)].
AB  - OBJECTIVES: To assess the burn-out syndrome in the population of urologists in
      training. MATERIAL AND METHODS: A trans-sectional study was carried out among the
      French urologists in training association (AFUF) members. A questionnaire
      including the Maslach Burnout Inventory and questions on the age, gender,
      professional and familial status, working time and hobbies was emailed. RESULTS:
      The response rate was 65.5 %. Mean burn-out, emotional exhaustion and
      depersonalization scores were 15.57 +/- 8.55 (low burn-out), 8.56 +/- 5.52
      (moderate burn-out) and 37.19 +/- 6.21 (moderate burn-out), respectively. Forty
      five (24 %) had a severe burn-out syndrome, 11 an emotional exhaustion and 41 a
      depersonalization. Urologists in couple had a significant lower emotional
      exhaustion level than single. Depersonalization and low personal accomplishment
      scores were related to the age and working time. Having at least one hobby
      prevented emotional exhaustion and improved personal accomplishment levels.
      Gender had no impact on burn-out syndrome. CONCLUSION: Quarter of French
      urologists in training had a burn-out syndrome. Factors preventing it were
      working time reduction, being in couple and having at least one hobby. burn-out
      syndrome severity decreased with age and senior status.

PMID- 21943662
TI  - [Congenital buried penis in children].
AB  - PURPOSE: Congenital buried penis in children is an uncommon and poorly known
      entity. The aims of this study were to report an original technique for
      correction of buried penis and to evaluate its results. PATIENTS AND METHODS: It
      is a retrospective study of buried penis operated between November 1998 and May
      2009. The acquired concealed penis and hypospadias were excluded from this study.
      The procedure includes several stages: degloving of the penis through a ventral
      anchor-like incision; division of the adherent layers surrounding the corpora
      cavernosa; anchorage of the Buck's fascia to the corporeal albuginea at the base
      of the penis; and ventral cutaneous coverage. The long-term results were
      evaluated by the parents and the surgeon according to anatomical, functional and
      aesthetic criterion. RESULTS: Twenty-five boys were evaluated. The mean age at
      surgery was 27 months (seven days-120 months). Two children required an
      additional plasty. Results were satisfactory in 24 cases (96%). One child
      required a redo procedure for unsatisfactory outcome. Of seven children with
      redundant skin (28%), three underwent a complementary cutaneous excision.
      CONCLUSION: Congenital buried penis remains a controversial issue. Our technique
      was simple and easily reproducible. Voiding difficulties, urinary tract infection
      or strong parental request were the main indications of this surgery in our
      experience.

PMID- 21943663
TI  - [Signet-ring cell primitive bladder carcinoma: a rare and aggressive tumor].
AB  - We report the case of a single patient suffering of a primary signet-ring cell
      carcinoma of the urinary bladder. This histological subtype of primary bladder
      cancer is very rare. We thus want to emphasize on its pathological specificity in
      order to improve the postoperative strategic treatment, knowing it is a rare but
      very aggressive kind of tumor.

PMID- 21943664
TI  - A statewide outbreak of Cryptosporidium and its association with the distribution
      of public swimming pools.
AB  - In order to characterize the association between county-level risk factors and
      the incidence of Cryptosporidium in the 2007 Iowa outbreak, we used generalized
      linear mixed models with the number of Cryptosporidium cases per county as the
      dependent variable. We employed a spatial power covariance structure, which
      assumed that the correlation between the numbers of cases in any two counties
      decreases as the distance between them increases. County population size was
      included in the model to adjust for population differences. Independent variables
      included the number of pools in specific pool categories (large, small, spa,
      wading, waterslide) and pool-owner classes (apartment, camp, country club or
      health club, hotel, municipal, school, other) as well as the proportion of
      residents aged <5 years. We found that increases in the number of bigger pools,
      pools with more heterogeneous mixing (municipal pools vs. country club or
      apartment pools), and pools catering to young children (wading pools) are
      associated with more cases at the county level.

PMID- 21943665
TI  - BRCA1 and BRCA2 variants of uncertain significance. Part two: medical management.

PMID- 21943666
TI  - Introduction: advances in myelodysplastic syndromes.

PMID- 21943667
TI  - Molecular biology of myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS) are a group of clonal hematopoetic disorders
      marked by ineffective hematopoiesis, peripheral cytopenias, and an increased risk
      of transformation to acute myeloid leukemia. Multiple processes govern
      hematopoietic progenitor proliferation and natural differentiation into mature
      myeloid elements. Molecular events that disrupt any of these processes have the
      potential to lead to ineffective hematopoiesis and an MDS phenotype. Recent
      advances in genomic analysis have identified a number of new genes that may be
      involved. The molecular description of MDS will lead to better understanding,
      classification, and treatment of this disease.

PMID- 21943668
TI  - Molecular dissection of the 5q deletion in myelodysplastic syndrome.
AB  - The 5q-syndrome is a subtype of myelodysplastic syndrome (MDS) with a defined
      clinical phenotype associated with heterozygous deletions of chromosome 5q. While
      no genes have been identified that undergo recurrent homozygous inactivation,
      functional studies have revealed individual genes that contribute to the clinical
      phenotype of MDS through haplo-insufficient gene expression. Heterozygous loss of
      the RPS14 gene on 5q leads to activation of p53 in the erythroid lineage and the
      macrocytic anemia characteristic of the 5q-syndrome. The megakaryocytic and
      platelet phenotype of the 5q-syndrome has been attributed to heterozygous
      deletion of miR145 and miR146a. Murine models have implicated heterozygous loss
      of APC, EGR1, DIAPH1, and NPM1 in the pathophysiology of del(5q) MDS. These
      findings indicate that the phenotype of MDS patients with deletions of chromosome
      5q is due to haplo-insufficiency of multiple genes.

PMID- 21943669
TI  - Classification and prognostic evaluation of myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS) are myeloid neoplasms characterized by dysplasia
      in one or more cell lines and increased risk of development of acute myeloid
      leukemia (AML). The current diagnostic approach to MDS includes peripheral blood
      and bone marrow morphology to evaluate abnormalities of peripheral blood cells
      and hematopoietic precursors; bone marrow biopsy to assess marrow cellularity,
      fibrosis, and topography; and cytogenetics to identify non-random chromosomal
      abnormalities. The 2008 World Health Organization (WHO) classification currently
      provides the best diagnostic approach to MDS and also has considerable prognostic
      relevance. The WHO classification-based prognostic scoring system (WPSS) is able
      to classify MDS patients into five risk groups showing different survivals and
      probabilities of leukemic evolution. The WPSS is able to predict survival and
      leukemia progression at any time during follow-up, and can therefore be used for
      implementing risk-adapted treatment strategies in patients with primary MDS.
      Since comorbidities have a significant impact on the outcome of patients with
      MDS, accounting for both disease status and comorbid conditions considerably
      improves risk stratification.

PMID- 21943670
TI  - Hematopoietic growth factors in myelodysplastic syndromes.
AB  - Hematopoietic growth factors (HGFs) continue to be the most widely prescribed
      class of medications for patients with myelodysplastic syndromes (MDS), despite
      the advent of disease-modifying therapies for MDS (eg, azacitidine, decitabine,
      and lenalidomide) and the current absence of an MDS-specific US Food and Drug
      Administration (FDA)-approved indication for any of the HGFs. Erythropoiesis
      stimulating agents (ESAs: epoetin alfa, darbepoetin alfa), myeloid growth factors
      (MGFs: filgrastim, pegfilgrastim, sargramostim), and the newest group of HGFs,
      thrombopoiesis-stimulating agents (TSAs: romiplostim, eltrombopag), can increase
      peripheral blood counts in some patients, and may ameliorate some of the signs
      and symptoms of MDS-associated bone marrow failure. Although HGFs are generally
      considered "supportive care" measures, recent data suggest that HGFs may alter
      the natural history of disease in MDS, either for better or worse. This review
      examines data on the safety and effectiveness of HGFs for patients with MDS.

PMID- 21943671
TI  - Role of lenalidomide in the treatment of myelodysplastic syndromes.
AB  - Lenalidomide is characterized as an immunomodulatory drug (IMiD), a second
      generation drug in this proprietary drug class with greater potency and a
      toxicity profile that is distinct from the lead compound, thalidomide. Clinical
      trials exploring its role in treating patients with myelodysplastic syndrome
      (MDS) revealed unique karyotype-specific activity in patients with interstitial
      deletion of the long arm of chromosome 5 (del(5q)). This observation ultimately
      led the US Food and Drug Administration (FDA) to approve lenalidomide for the
      treatment of lower risk transfusion-dependent patients with del(5q) MDS. Herein
      we review the results of four clinical trials conducted with lenalidomide in
      lower risk MDS, summarizing the clinical efficacy and safety of the drug. We
      discuss the use of lenalidomide in non-del(5q) patients and efforts to optimize
      its activity, in addition to investigations exploring the role of lenalidomide in
      higher risk MDS and acute myeloid leukemia (AML). Finally, we highlight the
      current understanding of its mechanism of action, discussing the emerging insight
      into the underlying biology of del(5q) MDS and its linkage to potential targets
      of lenalidomide.

PMID- 21943672
TI  - Integrating care for patients with lower risk myelodysplastic syndrome.
AB  - Patients with lower risk myelodysplastic syndrome (MDS) are those with low or
      intermediate-1 (INT-1) risk disease by the International Prognostic Scoring
      System (IPSS) index. Traditionally this has been a subset of patients where the
      philosophy of therapy has focused on improving transfusion needs. This is the
      result of the perception that the natural course of patients with lower risk
      disease is benign and the correct assumption that forms of therapy associated
      with early induction mortality cannot be justified. Over the last 5 years, we
      have witnessed significant improvements in our understanding of the natural
      history and therapy of patients with lower risk MDS. That said, it is not clear
      that any of these approaches improves survival. In this chapter, I will try to
      integrate information provided in other articles presented in this issue of
      Seminars in Oncology with new information regarding the heterogeneity of the
      natural history of patients with lower risk MDS and propose a framework for
      future research initiatives for this group of patients.

PMID- 21943673
TI  - Immunologic aspects of hypoplastic myelodysplastic syndrome.
AB  - The pathophysiology of myelodysplastic syndromes (MDS) is multiple, complex, and
      poorly understood. In some cases of MDS, especially those in which the bone
      marrow is hypocellular, there is increasing experimental and clinical indication
      that an immune-mediated damage to hematopoietic precursors and changes in the
      hematopoiesis-supporting microenvironment contribute to disease development.
      Increased serum levels of type-1 cytokines, tumor necrosis factor-alpha (TNF
      alpha), and interferon-gamma (INF-gamma), and oligoclonal expansion of cytotoxic
      T cells are observed in human MDS. In some cases, the immunologic attack to the
      marrow appears to be triggered by MDS-specific antigens, damaging the
      microenvironment and inducing cell apoptosis especially of normal progenitors. In
      murine models, dysregulation of osteoprogenitors leads to disrupted hematopoiesis
      of healthy hematopoietic progenitor and stem cells, eventually resulting in MDS
      and leukemia. In hypocellular MDS, marrow failure appears to be not only the
      result of ineffective erythropoiesis of abnormal clones, but also due to
      inhibition of normal progenitors. Immunosuppressive therapy with cyclosporine,
      anti-thymocyte globulin, or alemtuzumab may alleviate cytopenias and in some
      instances induce cytogenetic remission. However, not all patients respond to
      immunosuppression, and the identification of relevant biomarkers for an immune
      mechanism is necessary to identify those patients who may benefit from this
      treatment modality.

PMID- 21943674
TI  - Treatment of higher-risk myelodysplastic syndrome.
AB  - The myelodysplastic syndromes (MDS) are divided into lower-risk and higher-risk
      categories. This differentiation is important for treatment selection. Over the
      last decade, we have witnessed significant improvements in the treatment of
      patients with higher-risk MDS that have resulted in improved survival with the
      hypomethylating agent 5-azacytidine This has resulted in a shift from the use of
      acute myelogenous leukemia (AML)-like therapies, which were traditionally offered
      to this group of patients in the past, to the hypomethylating agents, which have
      become the standard of care. Despite these advances, new therapies or
      combinations are needed to improve response and survival rates. This review will
      summarize results from current available therapies and discuss potential needs
      and ongoing research in the area of treatment of higher-risk MDS.

PMID- 21943676
TI  - Hematopoietic stem cell transplantation for myelodysplastic syndrome: a review.
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) continues to be the
      only curative option for myelodysplastic syndrome (MDS). Since the majority of
      the patients with this disease are often older and frail, treatment-related
      mortality and morbidity remain major obstacles to be overcome. Reduced-intensity
      conditioning and continued lines of investigation in the field of allogeneic
      transplantation are expected to ultimately improve the overall therapeutic
      approach to MDS. In this review we summarize current recommendations and
      controversies surrounding HSCT for MDS, as well as the use of novel therapeutics
      in the peri-transplant period.

PMID- 21943675
TI  - Failure of hypomethylating agent-based therapy in myelodysplastic syndromes.
AB  - Hypomethylating agents such as 5-azacytidine or decitabine have been a major
      breakthrough in the treatment of patients with myelodysplastic syndromes (MDS).
      They have been shown to improve transfusion requirements and to change the
      natural history of the disease. However, with increasing cumulative clinical
      experience, it has become apparent that these agents are not curative and have
      their own shortcomings. There is a subgroup of patients who do not respond to
      frontline therapy and a large, growing cohort of patients that lose response or
      progress while on hypomethylating agent-based therapy. There are no standard
      treatment options in this arena and it is therefore a focus of significant
      research interest. Since the mechanisms of resistance to hypomethylating agents
      are not known, selection of therapy is largely empiric but must take into account
      the age, comorbidities, and performance status of the patient, as well as the
      characteristics of the disease at the time of treatment failure. Higher intensity
      approaches and allogeneic stem cell transplant can yield improved response rates
      and long-term disease control but should be limited to a selected cohort of
      patients who can tolerate the treatment-related morbidities. For the majority of
      patients who likely will be better candidates for lower intensity therapy,
      several novel, investigational approaches are becoming available. Among these are
      newer nucleoside analogues, inhibitors of protein tyrosine kinases, molecules
      that interact with redox signaling within the cell, immunotherapy approaches, and
      others. Patients with MDS whose disease has failed to respond to hypomethylating
      agent therapy should be referred for clinical trials when available. As we learn
      more about the patterns and mechanisms of failure, the next challenge will be to
      determine which therapies are suitable for each individual patient.

PMID- 21943677
TI  - The spatial distribution of bacteria in Grana-cheese during ripening.
AB  - The microbial composition and its spatial distribution of Grana Trentino, a hard
      Parmesan-like cheese, was determined, from vat milk to cheese. After cutting
      along the vertical axis of the cheese wheels, three layers were sampled
      diagonally across the cheese: under the cheese rind, an intermediate section and
      the cheese core. After two different ripening periods (9 and 18 months), the
      cheese samples were analysed using traditional culture dependent and culture
      independent methods. Milk samples were dominated by mesophilic and psychrophilic
      bacterial counts. Thermophilic bacteria (Lactobacillus helveticus) were found in
      high amounts in cooked whey and natural whey starter cultures. After 9 months of
      ripening, lactic acid bacteria (LAB) counts were higher than those after 18
      months. Furthermore, the LAB numbers in the cheese core was lower than those
      under the rind or in the intermediate section. The main LAB species isolated from
      milk (Lactococcus lactis, Pediococcus pentosaceus, Streptococcus uberis and
      Lactococcus garvieae) were not found in the corresponding cheeses. Some
      differences were observed in the species composition among the three cheese
      sections. Microbiota under the rind and in the intermediate section was similar
      and dominated by Lactobacillus paracasei and Lactobacillus rhamnosus. The core,
      after 18 months of ripening, was characterized by a total absence of LAB. In each
      sample, all LAB were genotypically grouped and the different biotypes were
      subjected to several technological tests indicating that some non-starter LAB
      (NSLAB) displayed technological features that are favorable for the production of
      Grana Trentino cheese.

PMID- 21943678
TI  - Comparison of genotypic and phenotypic cluster analyses of virulence determinants
      and possible role of CRISPR elements towards their incidence in Enterococcus
      faecalis and Enterococcus faecium.
AB  - Enterococcus faecalis and Enterococcus faecium are human commensals frequently
      found in fermented foods or used as probiotics, but also recognized as
      opportunistic pathogens. We investigated 62 Enterococcus strains isolated from
      clinical, food and environmental origins towards a rationale for safety
      evaluation of strains in food or probiotic applications. All isolates were
      characterised with respect to the presence of the virulence determinants fsrB,
      sprE, gelE, ace, efaAfs/fm, as, esp, cob and the cytolysin operon. In addition
      RAPD-PCR was used to obtain genomic fingerprints that were clustered and compared
      to phenotypic profiles generated by MALDI-TOF-MS. The gelatinase phenotype (GelE)
      and the haemolytic activity (beta-haemolysis) were analysed. E. faecium strains
      contained esp and efaAfm only, and none of them contained any CRISPR elements.
      The amenability of E. faecalis strains to acquisition of virulence factors was
      investigated along the occurrence of CRISPR associated (cas) genes. While
      distribution of most virulence factors, and RAPD versus MALDI-TOF-MS typing
      patterns were unrelated, 2 out of 5 RAPD clusters almost exclusively contained
      clinical E. faecalis isolates, and an occurrence of CRISPR elements versus
      reduced number of virulence factors was observed. The presence of the cytolysin
      operon, cob and as encoding pheromone and aggregation substance, respectively,
      significantly corresponded to absence of cas. As their production promote genetic
      exchange, their absence limits further gene acquisition and distribution. Thus,
      absence of the cytolysin operon, cob and as in a cas positive environment
      suggests itself as promising candidate for E. faecalis evaluation towards their
      occurrence in food fermentation or use as probiotics.

PMID- 21943679
TI  - A sensate superficial circumflex iliac perforator flap based on lateral cutaneous
      branches of the intercostal nerves.

PMID- 21943680
TI  - Reconstruction of periorbital defects following malignant tumour excision: a
      report of 50 cases.
AB  - BACKGROUND: Treatment in malignant periorbital tumours requires a radical
      resection of the tumour, and reconstruction of eyelid defects is difficult task
      because it should aim at gaining functional and aesthetical improvement. METHODS:
      We have reviewed 50 cases of malignant periorbital tumour that were treated
      surgically from 1992 to 2010. We assessed the type of reconstruction performed,
      and present or absent of any complication. RESULTS: The decision of the
      appropriate reconstructive procedure was based on the location of the tumour and
      the size of the defects. For the upper eyelid, switch flap from lower lid was
      performed in 11 out of 14 patients those defects exceeding 50% of the horizontal
      length. There were 21 complications (42%); major complications in 11 patients
      (22%) and minor complications in 10 patients (20%). Major complications have
      occurred only in upper eyelid or in lower eyelid. All of the major complications
      appeared in the patients with larger defects exceeding 50%. CONCLUSIONS: The 72%
      of major complications were associated with reconstruction of larger defects in
      upper eyelid. It might be extremely difficult to obtain good results in the
      patients with large upper eyelid defects, although switch flap is applicable to
      such defects.

PMID- 21943681
TI  - Extension of the jejunum in the reconstruction of cervical oesophagus with free
      jejunum transfer using the thoracoacrominal vessels as recipients.
AB  - BACKGROUNDS: The degree to which the jejunum can reach upward is a significant
      consideration in cervical oesophagus reconstruction with vascularised free
      jejunum transfer using the thoracoacrominal vessels as recipient vessels. The
      present study aims to elucidate this issue. MATERIALS AND METHODS: In 30 fresh
      cadavers, the thoracoacrominal vessels were dissected, and the jejunums were
      harvested, carrying the second branches of the superior mesenteric arteries and
      veins as their pedicles. After the mesenteric vessels were anastomosed to the
      thoracoacrominal vessels, the jejunums were advanced to their maximum upward
      degree, and the positions of the oral ends were evaluated referring to the hyoid
      bone. The evaluation was performed under three conditions. In the first
      condition, the jejunums were simply advanced. In the second condition, tension of
      the mesenteriums was reduced by incising their serosa. In the third condition,
      mesenterial incision was also performed, and the anastomosed pedicles were placed
      under the clavicles. RESULTS: The jejunums can reach superior to the hyoid bone
      by 2.1 +/- 1.5 SD cm for males and by 1.9 +/- 1.5 SD for females. By incising the
      mesenteric serosa, these distances can be extended by about 2 cm for males and 1
      cm for females. Further extension of 2 cm can be obtained for both sexes by
      placing the pedicle under the clavicle. CONCLUSION: With patients whose neck
      regions lack vessels available for vascular anastomosis, the thoracoacrominal
      vessels are used in free jejunum transfer for cervical oesophagus reconstruction.
      The findings of the present study are useful in planning this type of
      reconstruction.

PMID- 21943683
TI  - Network-based functional modeling of genomics, transcriptomics and metabolism in
      bacteria.
AB  - Molecular entities present in a cell (mRNA, proteins, metabolites,...) do not act
      in isolation, but rather in cooperation with each other to define an organisms
      form and function. Their concerted action can be viewed as networks of
      interacting entities that are active under certain conditions within the cell or
      upon certain environmental signals. A main challenge in systems biology is to
      model these networks, or in other words studying which entities interact to form
      cellular systems or accomplish similar functions. On the contrary, viewing a
      single entity or an experimental dataset in the light of an interaction network
      can reveal previous unknown insights in biological processes. In this review we
      give an overview of how integrated networks can be reconstructed from multiple
      omics data and how they can subsequently be used for network-based modeling of
      cellular function in bacteria.

PMID- 21943682
TI  - The effect of surgical and chemical denervation on ischaemia/reperfusion injury
      of skeletal muscle.
AB  - INTRODUCTION: Denervation decreases skeletal muscle's energy needs and alters its
      metabolism and circulation. Our study was designed in two stages to investigate
      the effects of surgical and chemical denervation on the ischaemia/reperfusion
      injury of skeletal muscle. Degenerative histological analysis, apoptosis scoring
      and tissue levels of malonyl-di-aldehyde (MDA) and nitric oxide end products
      (NOx) were studied to understand the extent of ischaemia/reperfusion injury of
      skeletal muscles. MATERIALS-METHODS: In the first stage, the effect of surgical
      denervation was investigated in four groups each containing six rats. The right
      biceps femoris muscle was used as the experimental muscle flap model. In the
      control group, only the ischaemia/reperfusion cycle was applied. Ischaemia was
      created by a tourniquet strictly wrapping the right lower extremity for 4 h.
      After ischaemia, the tourniquet was cut, and the extremity was reperfused for
      another 4 h. In the experimental groups, surgical denervation was applied 1 day,
      7 days and 30 days before the ischaemia/reperfusion cycle. On the second stage,
      the effect of chemical denervation with botulinum toxin type-A (BoNT-A) was
      investigated in three groups, each containing six rats. In the experimental
      groups, BoNT-A was applied 1 day, 7 days and 30 days before the
      ischaemia/reperfusion cycle. RESULTS: The control group had the worst scores in
      all experiment parameters. Degenerative histology and apoptosis scores were
      significantly better in groups to which BoNT-A and SD were applied 1 or 7 days
      before the ischaemia/reperfusion cycle. Regarding tissue levels of MDA and NOx,
      the experiment groups had significantly better scores comparing to the control
      group. CONCLUSION: Both surgical and chemical denervation applied before muscle
      transfer increased muscle ischaemia tolerance. With similar experimental
      outcomes, denervation with BoNT-A can be preferred to surgical denervation
      because of its abundant clinical availability and it can be applied without any
      secondary surgery.

PMID- 21943685
TI  - Structure and diversity of Erica ciliaris and Erica tetralix heathlands at
      different successional stages after cutting.
AB  - In NW Europe, it is known that cutting is a useful tool for managers with regard
      to decisions about the conservation and management of wet heathlands.
      Nevertheless it is rarely described quantitatively in the international
      literature. In Spain, knowledge about this is scarce or lacking. In this study,
      twenty communities were selected in Galicia (NW Spain) that would represent from
      one to four stages of vegetation development after cutting. Two 5 * 5 m plots
      were established for each stage to characterise the vegetation on the basis of
      its species composition, frequency values, vertical structure and linear cover
      features. The Diversity Shannon index was calculated and multivariate analyses
      were performed. As succession advanced, notable changes were produced in the
      cover of dominant species, Erica ciliaris and Ulex gallii in the first stages and
      Erica tetralix and Genista berberidea in mature ones. Also, the species richness
      decreased because of the reduced number of herbs species in the mature stages
      and, finally, the cover values are indicators of the degree of vegetation
      development, together with the other parameters of height, overlayering or
      diversity. Cutting is a useful tool for management of heathlands because the
      existence of vegetation units belonging to different succession stages increases
      the internal diversity of communities. On the other hand, the vertical and
      horizontal structure reflects the formidable resilience of the vegetation
      community to this practice. This study offers a global vision of the dynamics of
      wet heathlands after cutting, with very useful ecological information that can be
      used by the people responsible for their management.

PMID- 21943684
TI  - Nuclear factor erythroid-derived 2-like 2 (Nrf2) and DJ1 are prognostic factors
      in lung cancer.
AB  - Nuclear factor erythroid-derived 2-like 2 (Nrf2) controls the expression of
      several enzymes that are protective against oxidative stress. We investigated the
      expression of nuclear factor erythroid-derived 2-like 2, DJ1 (Nrf2 stabilizer),
      and sulfiredoxin in a large set of lung carcinomas. The cases were analyzed
      immunohistochemically with antibodies to nuclear factor erythroid-derived 2-like
      2, DJ1, and sulfiredoxin with the results being compared with histologic and
      clinical data. Significant differences were observed in the expression of DJ1 and
      sulfiredoxin between various types of lung tumors, while expression of nuclear
      factor erythroid-derived 2-like 2 was more constant. Patients with tumors with
      cytoplasmic (P = .033) or nuclear (P = .003) DJ1 positivity exhibited worse
      survival. Separately in squamous cell carcinomas, there was a tendency toward
      worse survival with both cytoplasmic (P = .013) and nuclear (P = .071) DJ1
      positivity. Patients with a strong nuclear factor erythroid-derived 2-like 2
      expression in their tumors had worse survival (P = .006). In the Cox regression
      analysis, nuclear factor erythroid-derived 2-like 2 was an independent prognostic
      factor (P = .012) along with the T status (P = .008) and DJ1 cytoplasmic
      positivity (P = .028). Interestingly, smokers and ex-smokers had significantly
      more sulfiredoxin expression in their tumors (P < .001); and in patients
      receiving cytostatic drugs or radiation therapy, sulfiredoxin expression
      predicted a poor prognosis (P = .038). Nuclear factor erythroid-derived 2-like 2
      and its stabilizing protein DJ1 affect the prognosis of patients with lung cancer
      by inducing an elevated stress response to oxidative damage. There were
      differences in the expression of sulfiredoxin and DJ1 between different lung
      tumor types, suggesting that the pathways involved in combating oxidative stress
      vary in different lung cancer types.

PMID- 21943686
TI  - Food, science, expertise.

PMID- 21943687
TI  - Combined estrogen-progestogen but not progestogen-only oral contraceptive alters
      glucose tolerance and plasma lipid profile in female rats.
AB  - Women are exposed to sex steroids in several formulations such as oral
      contraceptives (OCs) and hormone replacement therapies. Estrogen is believed to
      have cardiometabolic protection effect; but its beneficial effects have recently
      been queried. The aim of the present study was to clarify whether or not the
      altered glucose tolerance and plasma lipid profile was associated with OC and due
      to the estrogenic or progestogenic-component and if that was dose-dependent in 7
      8 weeks old female rats. Rats were divided into vehicle-treated (control), high
      dose combined OC-treated (HCOC; receiving 1.5MUg ethinyl estradiol/15.0MUg
      norgestrel), low dose combined OC-treated (LCOC; receiving 0.15MUg ethinyl
      estradiol/1.5MUg norgestrel), high dose progestogen OC-treated (HOC; receiving
      35.0MUg levonorgestrel) and low dose progestogen OC-treated (LOC; receiving
      3.5MUg levonorgestrel) groups. Rats were given (p.o.) vehicle (distilled water),
      HCOC, LCOC, HOC and LOC daily for 6 weeks. When compared with the controls, HCOC
      treatment led to significant decreases in glucose tolerance and plasma high
      density lipoprotein-cholesterol. However, HCOC-treated and LCOC-treated groups
      had significantly higher plasma triglyceride levels when compared with the
      control group. Fasting blood glucose, plasma total cholesterol, and low-density
      lipoprotein-cholesterol were comparable among groups. Body weight gain appeared
      to be attenuated by OC treatments, particularly in LOC-treated rats. In
      conclusion, our findings demonstrate that combined estrogen-progestogen but not
      progestogen-only OC use resulted in impaired glucose tolerance that was
      associated with increased triglyceride and decreased high-density lipoprotein
      cholesterol. The effects on glucose tolerance and high-density lipoprotein
      cholesterol were dose-dependent while that on triglyceride was not.

PMID- 21943688
TI  - Proliferation of rat mesenchymal stem cells in collagen sponges reinforced with
      poly(ethylene terephthalate) fibers by stirring culture method.
AB  - The objective of this study is to investigate the effect of medium stirring
      conditions on the proliferation of rat mesenchymal stem cells (MSC) in collagen
      sponges reinforced by the incorporation of poly(ethylene terephthalate) (PET)
      fibers. A collagen solution with PET fibers homogeneously dispersed was freeze
      dried, followed by dehydrothermal cross-linking to obtain a collagen sponge
      incorporating PET fibers. MSC were proliferated in the sponge by a stirring
      culture method. The PET fibers reinforcement significantly suppressed the sponge
      deformation in culture. The MSC proliferation was enhanced by the stirring
      culture to a significantly higher extent than that of a static one. Homogeneous
      distribution of cells proliferated was observed at the stirring rate of 50 rpm
      and compared with that at lower and higher rates. Combination of the PET fiber
      reinforced sponge with the stirring culture method is a promising way to allow
      cells to homogeneously proliferate in the sponge. 

PMID- 21943689
TI  - Malaria: control vs elimination vs eradication.

PMID- 21943690
TI  - Gender empowerment: beyond education.

PMID- 21943691
TI  - New US target to prevent 1 million heart attacks and strokes.

PMID- 21943693
TI  - Alice Roberts: the skull beneath the skin.

PMID- 21943694
TI  - Infectious disease control in Brazil.

PMID- 21943695
TI  - Infectious disease control in Brazil.

PMID- 21943696
TI  - Infectious disease control in Brazil.

PMID- 21943698
TI  - Epileptologists struggle to make their voices heard.

PMID- 21943699
TI  - Inequities in suicide prevention in Brazil.

PMID- 21943700
TI  - Cardiotocography and ST analysis for intrapartum fetal monitoring.

PMID- 21943702
TI  - Liver mass in a young adult.

PMID- 21943703
TI  - Biodiversity and ecosystem services: a multilayered relationship.
AB  - The relationship between biodiversity and the rapidly expanding research and
      policy field of ecosystem services is confused and is damaging efforts to create
      coherent policy. Using the widely accepted Convention on Biological Diversity
      definition of biodiversity and work for the U.K. National Ecosystem Assessment we
      show that biodiversity has key roles at all levels of the ecosystem service
      hierarchy: as a regulator of underpinning ecosystem processes, as a final
      ecosystem service and as a good that is subject to valuation, whether economic or
      otherwise. Ecosystem science and practice has not yet absorbed the lessons of
      this complex relationship, which suggests an urgent need to develop the
      interdisciplinary science of ecosystem management bringing together ecologists,
      conservation biologists, resource economists and others.

PMID- 21943704
TI  - The burden of infectious intestinal disease (IID) in the community: a survey of
      self-reported IID in The Netherlands.
AB  - In 2009, a 1-year retrospective survey was performed in The Netherlands to
      estimate the incidence and the disease burden of infectious intestinal disease
      (IID) in the community, to study the selection of patients consulting a general
      practitioner and to identify potential risk factors for IID in the community. A
      questionnaire was sent to 6000 persons selected at random from the population
      registries of 28 municipalities, with 500 persons being approached per month. A
      total of 1975 (33%) persons participated. The incidence rate of IID was 964/1000
      person-years. Potential risk factors associated with IID in the community were
      young age (0-4 years) [odds ratio (OR) 3.9, 95% confidence interval (CI) 1.5
      10.5], having asthma as a child (OR 3.4, 95% CI 1.1-10.3) and use of gastric acid
      suppressive medication by persons aged >= 45 years (OR 2.8, 95% CI 1.4-5.6). Of
      the 146 cases with IID, 11 (8%) consulted a physician. Cases with a long duration
      of symptoms, blood in the stool, children with IID and cases with a low level of
      education were more likely to consult a physician. Two cases had a stool sample
      taken and one was admitted to hospital. In conclusion, IID is common and has a
      significant burden of illness in The Netherlands. Our data indicate that about
      15.9 million episodes of IID occur in The Netherlands per year. The incidence
      rate is substantially higher than the rate of 283/1000 person-years as estimated
      in 1999 in The Netherlands. This is probably largely due to the retrospective
      nature of the present study and, to a lesser extent, to differences in case
      definitions.

PMID- 21943705
TI  - Structural basis of cross-allele presentation by HLA-A*0301 and HLA-A*1101
      revealed by two HIV-derived peptide complexes.
AB  - Human leukocyte antigens (HLA) are initially classified by serotyping but
      recently can be re-grouped by their peptide-presentation characteristics into
      supertypes. Both HLA-A*0301 and HLA-A*1101 are grouped into A3 supertype.
      Although a number of cross-presented T cell epitopes of HLA-A*0301 and HLA-A*1101
      have been identified, the molecular mechanisms of cross-presentation remain
      elusive. Herein, the structures of HLA-A*0301 with two HIV-derived immunodominant
      T cell epitopes were solved and their characteristics in comparison with HLA
      A*1101 presenting the same peptides were analyzed. The comparable structures of
      HLA-A*0301 and HLA-A*1101 with subtle differences illustrate the common modes of
      cross-presented peptides and the strict HLA-restriction of T cell receptor (TCR)
      recognition.

PMID- 21943706
TI  - Distinct roles of prostaglandin D2 receptors in chronic skin inflammation.
AB  - Prostaglandin D2 (PGD2) is a prostanoid implicated in allergic inflammation.
      However, the roles of PGD2 in immune and allergic responses remain controversial.
      PGD2 exerts its effect through the CRTH2 and DP receptors. To elucidate
      functional differences of PGD2 and its receptors in chronic skin inflammation,
      chronic contact hypersensitivity (chronic CHS) and IgE-mediated chronic allergic
      skin inflammation (IgE-CAI) were induced in mice deficient in the CRTH2 and/or DP
      genes. DP (-/-) mice and CRTH2 (-/-)/DP (-/-) mice showed exacerbated chronic
      CHS, and conversely, CRTH2 (-/-) mice exhibited diminished skin responses. Skin
      responses correlated with local levels of IL-13, CCL11, and CCL22. These
      phenotypic changes in chronic CHS of mutant mice were similar to those in acute
      CHS despite the differences in the cytokine milieus; chronic CHS and acute CHS
      were mediated by Th2 and Th1/Th17 immunity, respectively. However, in IgE-CAI, DP
      (-/-) mice showed comparable skin responses to wild-type mice. Alleviation of IgE
      CAI was observed in CRTH2 (-/-) mice, and as a consequence, CRTH2 (-/-)/DP (-/-)
      mice exhibited diminished IgE-CAI compared with wild-type mice. IgE-CAI in mutant
      mice correlated with local IL-4 and CCL22 production. Consistent with these
      results, a CRTH2-specific antagonist exerted inhibitory effects in both chronic
      CHS and IgE-CAI. The present study demonstrates that functional roles of PGD2 and
      its receptors appear to depend on the nature of the inflammation. Nevertheless,
      tools targeted against PGD2-CRTH2 signals could offer therapeutic potential for
      both types of chronic skin inflammation.

PMID- 21943707
TI  - Mitochondria as a sequestration site for incomplete TCRbeta peptides: the TCRbeta
      transmembrane domain is a sufficient mitochondrial targeting signal.
AB  - The existence of incomplete T cell receptor (TCR) mRNA forms, including germline
      transcripts and products of unfruitful TCR rearrangements, has long been known.
      However, it is unclear whether these molecules are functional. We have previously
      shown that T cells also contain truncated TCRbeta peptides that lack the N
      terminal part and contain C-terminus sequences. These partial forms of TCRbeta,
      target the mitochondrion and induce apoptosis, exhibiting a novel mode of TCR
      mediated cell death. Here we aimed at analyzing the minimal TCR sequences that
      direct the peptide to the mitochondrion. It is shown that truncated TCRbeta,
      targets mitochondria and induces mitochondrial perinuclear clustering, in both
      monkey COS-7 and human 293 cells. These phenomena are mediated by the C-terminus
      of the molecule. Whereas the positively charged amino acids flanking the
      transmembrane domain (TMD) of TCRbeta are beneficial for this process, they are
      not essential. Indeed, the isolated TMD of TCRbeta serves as a sufficient
      mitochondrial targeting sequence. These results indicate that any given partial
      form of TCRbeta, that contains the TMD, is bound to be sequestered by the
      mitochondrion. This may assure that incomplete TCR forms would not interfere with
      correct TCR complex formation.

PMID- 21943708
TI  - Mechanisms of mannose-binding lectin-associated serine proteases-1/3 activation
      of the alternative pathway of complement.
AB  - Mannose-binding lectin-associated serine proteases-1/3 (MASP-1/3) are essential
      in activating the alternative pathway (AP) of complement through cleaving pro
      factor D (pro-Df) into mature Df. MASP are believed to require binding to mannose
      binding lectins (MBL) or ficolins (FCN) to carry out their biological activities.
      Murine sera have been reported to contain MBL-A, MBL-C, and FCN-A, but not FCN-B
      that exists endogenously in monocytes and is thought not to bind MASP-1. We
      examined some possible mechanisms whereby MASP-1/3 might activate the AP.
      Collagen antibody-induced arthritis, a murine model of inflammatory arthritis
      dependent on the AP, was unchanged in mice lacking MBL-A, MBL-C, and FCN-A (MBL(
      /-)/FCN A(-/-) mice) in comparison to wild-type mice. The in vitro induction of
      the AP by adherent mAb to collagen II was intact using sera from MBL(-/-)/FCN A(
      /-) mice. Furthermore, sera from MBL(-/-)/FCN A(-/-) mice lacked pro-Df and
      possessed only mature Df. Gel filtration of sera from MBL(-/-)/FCN A(-/-) mice
      showed the presence of MASP-1 protein in fractions containing proteins smaller
      than the migration of MBL-A and MBL-C in sera from C4(-/-) mice, suggesting
      possible binding of MASP-1 to an unknown protein. Lastly, we show that FCN-B was
      present in the sera of MBL(-/-)/FCN A(-/-) mice and that it was bound to MASP-1.
      We conclude that MASP-1 does not require binding to MBL-A, MBL-C, or FCN-A to
      activate the AP. MASP-1 may cleave pro-Df into mature Df through binding to FCN-B
      or to an unknown protein, or may function as an unbound soluble protein.

PMID- 21943709
TI  - Cell type and gender-dependent differential regulation of the p202 and Aim2
      proteins: implications for the regulation of innate immune responses in SLE.
AB  - Upon sensing cytosolic double-stranded DNA (dsDNA), the murine Aim2 (encoded by
      the Aim2 gene) protein forms an inflammasome and promotes the secretion of
      proinflammatory cytokines, such as IL-1beta and IL-18. In contrast, the p202
      protein (encoded by the Ifi202 gene) does not form an inflammasome. Previously,
      we have reported that the interferon (IFN) and female sex hormone-induced
      increased nuclear levels of p202 protein in immune cells are associated with
      increased susceptibility to develop a lupus-like disease. However, signaling
      pathways that regulate the expression of Aim2 protein remain unknown. Here we
      report that the expression of Aim2 gene is induced in bone marrow-derived
      macrophages (BMDMs) by IFN-alpha treatment and the expression is, in part, STAT1
      dependent. However, treatment of splenic T or B cells with IFN-alpha or their
      stimulation, which induced the expression of Ifi202 gene, did not induce the
      expression of Aim2 gene. Furthermore, treatment of cells with the male hormone
      androgen increased levels of Aim2 mRNA and protein. Moreover, treatment of murine
      macrophage cell lines (RAW264.7 and J774A.1) with IFN-alpha differentially
      induced the expression of Aim2 and p202 proteins and regulated their sub-cellular
      localization. Additionally, activation of Toll-like receptors (TLR3, 4, and 9) in
      BMDMs and cell lines also differentially regulated the expression of Aim2 and
      Ifi202 genes. Our observations demonstrate that cell type and gender-dependent
      factors differentially regulate the expression of the Aim2 and p202 proteins,
      thus, suggesting opposing roles for these two proteins in innate immune responses
      in lupus disease.

PMID- 21943710
TI  - Crystal growth, structural, optical, dielectric and thermal studies of an amino
      acid based organic NLO material: L-phenylalanine L-phenylalaninium malonate.
AB  - Good transparent single crystals of L-phenylalanine L-phenylalaninium malonate
      (LPPMA) have been grown successfully by slow evaporation technique from aqueous
      solution. Single crystal X-ray diffractometer was utilized to measure unit cell
      parameter and to confirm the crystal structure. The chemical structure of
      compound was established by FT-NMR technique. The vibrational modes of the
      molecules of elucidated from FTIR spectra. Its optical behaviour has been
      examined by UV-vis spectral analysis, which shows the absence of absorbance in
      the visible region. Thermal properties of the LPPMA crystal were carried out by
      thermo gravimetric analysis (TGA) and differential thermal analysis (DTA)
      techniques, which indicate that the material does not decompose before melting.
      The melting point of grown crystal was observed as 180 degrees C by melting point
      apparatus. The NLO property was confirmed by the powder technique of Kurtz and
      Perry. The dielectric behaviour of the sample was also studied for the first
      time.

PMID- 21943711
TI  - The use of mobile Raman spectroscopy to compare three full-page miniatures from
      the Breviary of Arnold of Egmond.
AB  - The Breviary of Arnold of Egmond is one of the most wealthily illuminated
      fifteenth century manuscripts in the Northern Netherlands. The manuscript
      originally contained a number of full-page miniatures, which were all removed at
      an unknown date before 1902. The three remaining miniatures studied here, are
      today part of different collections, but they were brought together for an
      exhibition. Although several historical and art historical details of this
      breviary have extensively been studied, no examination of the materials used was
      undertaken before. Analytical techniques, such as mobile Raman spectroscopy, can
      be used to characterise and identify these materials in a non-invasive way. This
      paper presents the results of the in situ Raman analysis of three full-page
      miniatures of the Breviary of Arnold of Egmond. During this study, different
      pigments could be identified, such as lead white (2PbCO(3).Pb(OH)(2)), lead-tin
      yellow type I (Pb(2)SnO(4)), ultramarine (Na(8-10)Al(6)Si(6)O(24)S(2-4)),
      massicot (PbO), vermilion (HgS) and red lead (Pb(3)O(4)). Next to identification
      of the pigments, visual analysis was used to detect differences and similarities
      between the stylistic elements of the three analysed folios.

PMID- 21943712
TI  - Vibrational spectroscopy (FT-IR and FT-Raman) investigation, and hybrid
      computational (HF and DFT) analysis on the structure of 2,3-naphthalenediol.
AB  - The FT-IR and FT-Raman vibrational spectra of 2,3-naphthalenediol (C(10)H(8)O(2))
      have been recorded using Bruker IFS 66V spectrometer in the range of 4000-100 cm(
      1) in solid phase. A detailed vibrational spectral analysis has been carried out
      and the assignments of the observed fundamental bands have been proposed on the
      basis of peak positions and relative intensities. The optimized molecular
      geometry and vibrational frequencies in the ground state are calculated by using
      the ab initio Hartree-Fock (HF) and DFT (LSDA and B3LYP) methods with 6-31+G(d,p)
      and 6-311+G(d,p) basis sets. There are three conformers, C1, C2 and C3 for this
      molecule. The computational results diagnose the most stable conformer of title
      molecule as the C1 form. The isotropic computational analysis showed good
      agreement with the experimental observations. Comparison of the fundamental
      vibrational frequencies with calculated results by HF and DFT methods. Comparison
      of the simulated spectra provides important information about the capability of
      computational method to describe the vibrational modes. A study on the electronic
      properties, such as absorption wavelengths, excitation energy, dipole moment and
      Frontier molecular orbital energies, are performed by time dependent DFT
      approach. The electronic structure and the assignment of the absorption bands in
      the electronic spectra of steady compounds are discussed. The calculated HOMO and
      LUMO energies show that charge transfer occurs within the molecule. On the basis
      of the thermodynamic properties of the title compound at different temperatures
      have been calculated. The statistical thermodynamic properties (standard heat
      capacities, standard entropies, and standard enthalpy changes) and their
      correlations with temperature have been obtained from the theoretical vibrations.

PMID- 21943713
TI  - Experimental and theoretical study of two new pyrazoline derivatives based on
      dibenzofuran.
AB  - Two novel pyrazoline derivatives, named 2,8-bis(1,3-diphenyl-pyrazoline-5
      yl)dibenzofuran (A) and 2,8-bis(1-(4-bromophenyl)-3-phenyl-pyrazoline-5
      yl)dibenzofuran (B), were synthesized and characterized by elemental analysis,
      NMR, MS and thermogravimetric analysis. The absorption and emission spectra of
      them were determined by experimental methods in different polar solvents and were
      computed using the density functional theory (DFT) and the time-dependent density
      functional theory (TDDFT) at the same time. The calculated absorption and
      emission wavelengths are in good agreement with the experimental data. The
      fluorescence quantum yields and fluorescence lifetimes of them in different polar
      solvents were studied by means of steady state and time resolved fluorescence.
      The calculated reorganization energy for hole and electron indicates that the two
      compounds are in favor of hole transport than electron transport. The results
      show the two compounds present high fluorescence quantum yields and excellent
      thermal stability. It makes them of great interest as novel fluorescent probes
      and optoelectronic materials.

PMID- 21943714
TI  - Relative predominance of azo and hydrazone tautomers of 4-carboxyl-2,6
      dinitrophenylazohydroxynaphthalenes in binary solvent mixtures.
AB  - Azo-hydrazone tautomerism is a phenomenon that occurs in azo dyes possessing
      substituents conjugated to the azo linkage which has labile proton that can be
      exchanged intramolecularly. Thus the predominance of one tautomer over another is
      a function of many factors among which are solvent polarity, solvent type, solute
      solvent interactions and the structure of the dye molecule itself. The 4-carboxyl
      2,6-dinitrophenylazohydroxynaphthalenes, previously shown to exhibit azo
      hydrazone tautomerism, were studied for the relative predominance of one form
      over another based on interaction at the microenvironment of binary solvent
      mixtures containing DMF and non-hydrogen bonding (CCl(4)), hydrogen bond donor
      (toluene, chloroform), hydrogen bond acceptor (acetonitrile, acetone) and the
      alcohols; ethanol and methanol as solvent pairs. The three dyes gave two main
      bands in the 50:50 mixture of DMF with these solvents consisting of a high energy
      band at 250-382 nm while the low energy bands for the dyes occurred at 415-485
      nm. Spectral shifts in the binary solvent mixtures were related to the solvent
      dipolarity, basicity of the less polar component relative to DMF, substituent
      type, molar transition energy, formation constant for the hydrogen-bonding
      solvated complexes and the standard free energy change for hydrogen bonding with
      DMF. The relative predominance of the hydrazone tautomer bears a direct
      relationship to the basicity of the solvent, presence of hydrogen bond donor
      substituent and was associated with high molar transition energies and low
      formation constant. The microenvironment surrounding the dye molecules played a
      major role in the stability of one tautomer relative to the other.

PMID- 21943715
TI  - N,N'-dipyridoxyl Schiff bases: synthesis, experimental and theoretical
      characterization.
AB  - Three N,N'-dipyridoxyl Schiff bases (L1, L2 and L3) have been newly synthesized
      and characterized by IR, (1)H NMR, mass spectrometry and elemental analysis.
      Their optimized geometries together with the theoretical assignment of the
      vibrational frequencies and the (1)H NMR chemical shifts of them have been
      computed by using density functional theory (DFT) method. In the optimized
      structures of the Schiff bases, two pyridine rings are not in a same plane;
      however the substitutions are essentially in the same plane with the pyridine
      rings. Also, the benzene ring(s) in the bridge region is (are) not in the same
      plane with the pyridine rings and azomethine moieties. In all the species,
      engagement in intramolecular-hydrogen bonds causes to weakness of the phenolic O
      H bonds. Consistency between the theoretical results and experimental evidence
      confirms suitability of the optimized geometries for the synthesized Schiff
      bases.

PMID- 21943716
TI  - Quantum mechanical and spectroscopic (FT-IR, FT-Raman, 13C, 1H and UV)
      investigations of antiepileptic drug Ethosuximide.
AB  - The Fourier Transform Infrared (FT-IR) and Fourier Transform Raman (FT-Raman)
      spectra of antiepileptic drug Ethosuximide (ETX) have been recorded and analyzed.
      In addition, the IR spectra in CCl(4) at various concentrations of ETX are also
      recorded. The equilibrium geometry, bonding features and harmonic vibrational
      frequencies have been investigated with the help of Density Functional Theory
      (DFT) method. The (1)H and (13)C nuclear magnetic resonance (NMR) chemical shifts
      of the molecule were calculated by the Gauge Including Atomic Orbital (GIAO)
      method. Stability of the molecule arising from hyperconjugative interactions and
      charge delocalization has been analyzed using natural bond orbital (NBO)
      analysis. The results show that charge in electron density (ED) in the sigma* and
      pi* antibonding orbitals and second order delocalization energies E(2) confirms
      the occurrence of intramolecular charge transfer (ICT) within the molecule. UV
      vis spectrum of the compound was recorded and the electronic properties, such as
      HOMO and LUMO energies, were performed by Time-Dependent Density Functional
      Theory (TD-DFT) approach. Finally the calculation results were applied to
      simulate infrared and Raman spectra of the title compound which showed good
      agreement with observed spectra.

PMID- 21943717
TI  - Vibrational spectroscopy of the multi-anion mineral zykaite
      Fe4(AsO4)(SO4)(OH).15H2O-implications for arsenate removal.
AB  - Some minerals are colloidal and are poorly diffracting. Vibrational spectroscopy
      offers one of the few methods for the assessment of the structure of these types
      of minerals. Among this group of minerals is zykaite with formula
      Fe(4)(AsO(4))(SO(4))(OH).15H(2)O. The objective of this research is to determine
      the molecular structure of the mineral zykaite using vibrational spectroscopy.
      Raman and infrared bands are attributed to the AsO(4)(3-), SO(4)(2-) and water
      stretching vibrations. The sharp band at 3515 cm(-1) is assigned to the
      stretching vibration of the OH units. This mineral offers a mechanism for the
      formation of more crystalline minerals such as scorodite and bukovskyite.
      Arsenate ions can be removed from aqueous systems through the addition of ferric
      compounds such as ferric chloride. This results in the formation of minerals such
      as zykaite and pitticite (Fe(3+), AsO(4), SO(4), H(2)O).

PMID- 21943718
TI  - Fast screening of lovastatin in red yeast rice products by flow injection tandem
      mass spectrometry.
AB  - Drug adulteration in dietary supplement materials is a world-wide problem and
      poses a regulatory challenge. Red yeast rice is a product used by consumers to
      lower blood levels of cholesterol. While most current methods to analyze red
      yeast rice are based on HPLC separation with a photo-diode array detector and/or
      a mass spectrometry detector, which takes 20-40min analysis time per sample, we
      developed a method to do fast screening of the active compound lovastatin by
      direct infusion into a mass spectrometer. This method takes under 1min per
      analysis on the instrument. By using multiple reaction monitoring with five
      product ions, all the ion ratios of the analyte in the samples are compared with
      those from the standards for qualitative analysis. The results from this method
      were compared to the result from the liquid chromatography tandem mass
      spectrometry, which uses retention time and one ion ratio as the confirmation
      criteria. No false positives or false negatives were found among the 12 samples
      tested. The method also seems to be effective in measuring the lovastatin in red
      yeast rice semi-quantitatively. This kind of method could be adapted to the
      screening of other dietary supplement products.

PMID- 21943719
TI  - Diagnostic and therapeutic impact of MR enterography in Crohn's disease.
AB  - AIM: To assess the impact of magnetic resonance enterography (MRE) on clinician
      diagnostic confidence and therapeutic strategy in patients under investigation
      for small bowel Crohn's disease. MATERIAL AND METHODS: Gastroenterologists
      completed a proforma before and following MRE in 51 patients (mean age 35 years,
      26 female) under investigation for small bowel Crohn's disease, indicating
      percentage confidence for presence/absence of small bowel involvement. In
      suspected disease, diagnostic confidence (using a scoring system from 1=no to
      6=yes) was scored for subcategories: extent >30 cm (DE), terminal ileum (lTI),
      jejunal (JD), colonic disease (CoD), strictures (ST), activity (AD), extraluminal
      complications (EL), and surgical need (NS). Therapeutic strategy was recorded.
      Patients were divided into three groups: 1=suspected disease, MRE normal (n=15);
      2=suspected disease, MRE abnormal (n=30); 3=no suspected disease, MRE normal
      (n=6). Binomial exact and paired t-tests were use to compare confidence pre and
      post-MRE. RESULTS: Mean percentage confidence for the presence/absence of small
      bowel disease increased from 62 to 84% (p=0.003), 87 to 98% (p=0.0001), and 83 to
      98% (p=0.005) after MRE for groups 1, 2, and 3, respectively. In suspected
      disease, confidence changed significantly for all of the subcategories (p<0.001)
      except EL in group 1. The percentage of patients with a confidence change ranged
      from 40% (CoD) to 87% (lTI; group 1) and from 7% (EL) to 93% (DE; group 2).
      Therapeutic strategy changed in 31/51 (61%, 95% CI 47-74%), 14 with a reduction
      in planned therapy and 17 with an increase. CONCLUSION: MRE had a positive
      diagnostic impact in patients under investigation for small bowel Crohn's disease
      and this influenced therapeutic strategy in 61% of the patients.

PMID- 21943720
TI  - Tumour heterogeneity in oesophageal cancer assessed by CT texture analysis:
      preliminary evidence of an association with tumour metabolism, stage, and
      survival.
AB  - AIM: To undertake a pilot study assessing whether tumour heterogeneity evaluated
      using computed tomography texture analysis (CTTA) has the potential to provide a
      marker of tumour aggression and prognosis in oesophageal cancer. MATERIALS AND
      METHODS: In 21 patients, unenhanced CT images of the primary oesophageal lesion
      obtained using positron-emission tomography (PET)-CT examinations underwent CTTA.
      CTTA was carried out using a software algorithm that selectively filters and
      extracts textures at different anatomical scales between filter values 1.0 (fine
      detail) and 2.5 (coarse features) with quantification as entropy and uniformity
      (measures image heterogeneity). Texture parameters were correlated with average
      tumour 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG) uptake [standardized uptake
      values (SUV(mean) and SUV(max))] and clinical staging as determined by endoscopic
      ultrasound (nodal involvement) and PET-CT (distant metastases). The relationship
      between tumour stage, FDG uptake, and texture with survival was assessed using
      Kaplan-Meier analysis. RESULTS: Tumour heterogeneity correlated with SUV(max) and
      SUV(mean). The closest correlations were found for SUV(mean) measured as
      uniformity and entropy with coarse filtration (r=-0.754, p<0.0001; and r=0.748,
      p=0.0001 respectively). Heterogeneity was also significantly greater in patients
      with clinical stage III or IV for filter values between 1.0 and 2.0 (maximum
      difference at filter value 1.5: entropy: p=0.027; uniformity p=0.032). The median
      (range) survival was 21 (4-34) months. Tumour heterogeneity assessed by CTTA
      (coarse uniformity) was an independent predictor of survival [odds ratio
      (OR)=4.45 (95% CI: 1.08, 18.37); p=0.039]. CONCLUSION: CTTA assessment of tumour
      heterogeneity has the potential to identify oesophageal cancers with adverse
      biological features and provide a prognostic indicator of survival.

PMID- 21943721
TI  - Biodiversity, ecosystem functions and services in environmental risk assessment:
      introduction to the special issue.
AB  - This Special Issue focuses on the questions if and how biodiversity, ecosystem
      functions and resulting services could be incorporated into the Ecological Risk
      Assessment (ERA). Therefore, three articles provide a framework for the
      integration of ecosystem services into ERA of soils, sediments and pesticides.
      Further articles demonstrate ways how stakeholders can be integrated into an
      ecosystem service-based ERA for soils and describe how the current monitoring
      could be adapted to new assessment endpoints that are directly linked to
      ecosystem services. Case studies show that the current ERA may not be protective
      for biodiversity, ecosystem functions and resulting services and that both
      pesticides and salinity currently adversely affect ecosystem functions in the
      field. Moreover, ecological models can be used for prediction of new protection
      goals and could finally support their implementation into the ERA. Overall, the
      Special Issue stresses the urgent need to enhance current procedures of ERA if
      biodiversity, ecosystem functions and resulting services are to be protected.

PMID- 21943722
TI  - A high resolution temporal study of phytoplankton bloom dynamics in the eutrophic
      Taw Estuary (SW England).
AB  - The Taw Estuary (SW England) is eutrophic as a result of enhanced nutrient inputs
      from its catchment. However, factors influencing the timing and extent of
      phytoplankton bloom formation are not fully understood in this system. In this
      study, high resolution chemical and biological sampling was undertaken in late
      winter/spring and summer 2008 in order to gain further insights into bloom
      dynamics in the Taw Estuary. Temporal variations in chlorophyll a maxima in the
      upper and middle estuary during summer were controlled by river flow and tidal
      amplitude, with nutrient limitation probably less important. Concentrations of
      chlorophyll a were highest during low river flow and neap tides. Increased river
      flows advected the chlorophyll maximum to the outer estuary, and under highest
      river discharges, chlorophyll a concentrations were further reduced. This feature
      was even more pronounced when spring tides coincided with high flows. The main
      bloom species were the diatoms Asterionellopsis glacialis and Thalassiosira
      guillardii. Using two multivariate statistical techniques in combination, five
      distinct physical and biogeochemical states in the Taw estuarine waters were
      identified. These states can be summarised as: A(1), high chlorophyll a, high
      temperature, long residence times, nutrient depletion; A(2), strong coastal water
      influence; B(1), decreasing chlorophyll a, increasing river flow and/or spring
      tides; B(2), transitional between states A(1) and B(3); B(3), high river flow. It
      was thus possible to differentiate between contrasting environmental conditions
      that were either beneficial or detrimental for the development of algal blooms. A
      conceptual model of diatom - dominated primary production for the Taw Estuary is
      proposed which describes how physical controls (river flow, tidal state) moderate
      plankton biomass production in the upper and mid - estuarine regions.

PMID- 21943724
TI  - The sensitivity of fluvial flood risk in Irish catchments to the range of IPCC
      AR4 climate change scenarios.
AB  - In the face of increased flood risk responsible authorities have set out safety
      margins to incorporate climate change impacts in building robust flood
      infrastructure. Using the case study of four catchments in Ireland, this study
      subjects such design allowances to a sensitivity analysis of the uncertainty
      inherent in estimates of future flood risk. Uncertainty in flood quantiles is
      quantified using regionalised climate scenarios derived from a large number of
      GCMs (17), forced with three SRES emissions scenarios. In terms of hydrological
      response uncertainty within and between hydrological models is assessed using the
      GLUE framework. Regionalisation is achieved using a change factor method to infer
      changes in the parameters of a weather generator using monthly output from the
      GCMs, while flood frequency analysis is conducted using the method of probability
      weighted moments to fit the Generalised Extreme Value distribution to ~20,000
      annual maximia series. Sensitivity results show that for low frequency events,
      the risk of exceedence of design allowances is greater than for more frequent
      events, with considerable implications for critical infrastructure. Peak flows
      for the five return periods assessed were found to be less sensitive to
      temperature and subsequently to potential evaporation (PET) than to rainfall. The
      average width of the uncertainty range for changes in flood magnitude is greater
      for low frequency events than for high frequency events. In all catchments there
      is a progressive increase in the peak flows associated with the 5, 25, 50 and 100
      year return periods when moving from the 2020s to the 2080s.

PMID- 21943723
TI  - A longitudinal study of sick building syndrome among pupils in relation to
      microbial components in dust in schools in China.
AB  - There are few longitudinal studies on sick building syndrome (SBS), which include
      ocular, nasal, throat, and dermal symptoms, headache, and fatigue. We studied the
      associations between selected microbial components, fungal DNA, furry pet
      allergens, and incidence and remission of SBS symptoms in schools in Taiyuan,
      China. The study was based on a two-year prospective analysis in pupils (N=1143)
      in a random sample of schools in China. Settled dust in the classrooms was
      collected by vacuum cleaning and analyzed for lipopolysaccharide (LPS), muramic
      acid (MuA), and ergosterol (Erg). Airborne dust was collected in Petri dishes and
      analyzed for cat and dog allergens and fungal DNA. The relationship between the
      concentration of allergens and microbial compounds and new onset of SBS was
      analyzed by multi-level logistic regression. The prevalence of mucosal and
      general symptoms was 33% and 28%, respectively, at baseline, and increased during
      follow-up. At baseline, 27% reported at least one symptom that improved when away
      from school (school-related symptoms). New onset of mucosal symptoms was
      negatively associated with concentration of MuA, total LPS, and shorter lengths
      of 3-hydroxy fatty acids from LPS, C14, C16, and C18. Onset of general symptoms
      was negatively associated with C18 LPS. Onset of school-related symptoms was
      negatively associated with C16 LPS, but positively associated with total fungal
      DNA. In general, bacterial compounds (LPS and MuA) seem to protect against the
      development of mucosal and general symptoms, but fungal exposure measured as
      fungal DNA could increase the incidence of school-related symptoms.

PMID- 21943725
TI  - Dietary patterns and difficulty conceiving: a nested case-control study.
AB  - OBJECTIVE: To investigate potential associations between dietary patterns
      (defined using factor analysis) and difficulty conceiving. DESIGN: Case-control
      study nested in a Spanish cohort of university graduates (Seguimiento Universidad
      de Navarra [SUN] Project). SETTING: Female university graduates all over Spain
      participating in the SUN Project. PATIENT(S): A total of 485 women, aged 20-45
      years, reporting having presented with difficulty getting pregnant, and 1,669 age
      matched controls who had at least one child. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Reported difficulty getting pregnant. Data were collected from
      baseline and follow-up questionnaires of the SUN Project. RESULT(S): Two dietary
      patterns were identified. They were labeled as "Mediterranean-type" and "Western
      type" patterns. A lower risk of difficulty getting pregnant was apparent in the
      highest quartile of adherence to the Mediterranean-type pattern compared with the
      lowest quartile (odds ratio 0.56, 95% confidence interval 0.35-0.95). Greater
      adherence to the Western-type dietary pattern showed no association with this
      outcome. CONCLUSION(S): A greater adherence to the Mediterranean-type dietary
      pattern may enhance fertility. Further evidence about the relationship between
      this dietary pattern and fertility is needed to develop nutritional interventions
      for women desiring to get pregnant.

PMID- 21943726
TI  - Notch 1 signaling pathway effect on implantation competency.
AB  - OBJECTIVE: To investigate the relationship between the Notch 1 signaling pathway
      and the embryo implantation rate. DESIGN: Mouse embryos were cultured in vitro,
      and implantation competency was quantified. SETTING: Tertiary fertility center of
      a university teaching hospital. ANIMAL(S): Outbred ICR strain mouse embryos.
      INTERVENTION(S): The expression of Notch 1 was altered by adding a gamma
      secretase inhibitor to the culture medium. We quantified the consequent effect on
      embryo implantation. MAIN OUTCOME MEASURE(S): We measured the messenger RNA level
      of Notch 1 gene at different embryonic stages, embryo implantation rate under
      different culture conditions, the amount of Notch 1, and related implantation
      competency. RESULT(S): Quantitative polymerase chain reaction showed that the
      expression of Notch 1 increased during the implantation window. Adding gamma
      secretase inhibitor in the culture medium decreased the percentage of blastocysts
      in a dose-dependent manner. A Matrigel invasion assay showed that the competency
      of implantation required adequate expression of Notch 1 intracellular domain.
      CONCLUSION(S): Expression of Notch 1 at the proper time is required for the
      competency of embryo implantation; this effect is mediated through regulation of
      Notch 1 intracellular domain expression.

PMID- 21943727
TI  - Invited review: Application of omics tools to understanding probiotic
      functionality.
AB  - The human gut microbiota comprises autochthonous species that colonize and reside
      at high levels permanently and allochthonous species that originate from another
      source and are transient residents of the human gut. The interactions between
      bacteria and the human host can be classified as a continuum from symbiosis and
      commensalism (mutualism) to pathogenesis. Probiotics are live microorganisms
      that, when administered in adequate amounts, confer a health benefit on the host.
      Recent advances in omics tools and sequencing techniques have furthered our
      understanding of probiotic functionality and the specific interactions between
      probiotics and their human hosts. Although it is known that not all probiotics
      use the same mechanisms to confer benefits on hosts, some specific mechanisms of
      action have been revealed through omic investigations. These include competitive
      exclusion, bacteriocin-mediated protection against intestinal pathogens, intimate
      interactions with mucin and the intestinal epithelium, and modulation of the
      immune system. The ability to examine fully sequenced and annotated genomes has
      greatly accelerated the application of genetic approaches to elucidate many
      important functional roles of probiotic microbes.

PMID- 21943728
TI  - Microbial dynamics during the ripening of a mixed cow and goat milk cheese
      manufactured using frozen goat milk curd.
AB  - To overcome the seasonal shortage of goat milk in mixed milk cheese manufacture,
      pasteurized goat milk curd and high-pressure-treated raw goat milk curd
      manufactured in the spring were held at -24  degrees C for 4 mo, thawed, and
      mixed with fresh cow milk curd for the manufacture of experimental cheeses.
      Control cheeses were made from a mixture of pasteurized cow and goat milk. The
      microbiota of experimental and control cheeses was studied using culture
      dependent and culture-independent techniques. Bacterial enumeration by classical
      methods showed lactic acid bacteria to be the dominant population in both control
      and experimental cheeses. In total, 681 isolates were grouped by partial
      amplified rDNA restriction analysis (ARDRA) into 4 groups and identified by 16S
      rRNA gene sequencing as Lactococcus lactis ssp. lactis (563 isolates),
      Leuconostoc pseudomesenteroides (72 isolates), Lactobacillus spp. (34 isolates),
      and Lc. lactis ssp. cremoris (12 isolates). Temporal temperature gradient gel
      electrophoresis (TTGE) analysis of cheese showed (1) the predominance of Lc.
      lactis in all cheeses; (2) the presence of Leu. pseudomesenteroides population in
      all cheeses from d 15 onward; (3) the presence of a Lactobacillus plantarum
      population in control cheese until d 15 and in experimental cheeses throughout
      the ripening period. Due to the most diverse and complete set of peptidases
      present in the genus Lactobacillus, the prevalence of this population in
      experimental cheeses could give rise to differences in cheese flavor between
      experimental and control cheeses.

PMID- 21943729
TI  - Effect of the inoculation level of Lactobacillus acidophilus in probiotic cheese
      on the physicochemical features and sensory performance compared with commercial
      cheeses.
AB  - The complex metabolism of probiotic bacteria requires several technological
      options to guarantee the functionally of probiotic dairy foods during the shelf
      life. This research aimed to evaluate the effect of the supplementation of
      increasing amounts of Lactobacillus acidophilus (0, 0.4, or 0.8 g/L of milk) on
      the physicochemical parameters and sensory acceptance of Minas fresh cheese. In
      addition, the sensory acceptance of probiotic cheeses was assessed using a
      consumer test and compared with commercial cheeses (conventional and probiotic).
      High counts (9.11 to 9.42 log cfu/g) of L. acidophilus were observed throughout
      the shelf life, which contributed to the maintenance of its probiotic status and
      resulted in lower pH values and greater production of organic acids. The
      probiotic cheeses presented lower scores for appearance, aroma, and texture
      compared with conventional cheeses. Internal preference mapping explained almost
      60% of the total variation of the data and showed a large number of consumers
      concentrated near the conventional cheeses, demonstrating greater preference for
      these samples. The findings indicated that some negative sensory effects could
      occur when high level of supplementation with L. acidophilus is used in probiotic
      cheese processing.

PMID- 21943730
TI  - Composition and effect of blending of noncoagulating, poorly coagulating, and
      well-coagulating bovine milk from individual Danish Holstein cows.
AB  - The aim of the present investigation was to study the underlying causes of
      noncoagulating (NC) milk. Based on an initial screening in a herd of 53 Danish
      Holstein-Friesians, 20 individual Holstein-Friesian cows were selected for good
      and poor chymosin-induced coagulation properties; that is, the 10 cows producing
      milk with the poorest and best coagulating properties, respectively. These 20
      selected cows were followed and resampled on several occasions to evaluate
      possible changes in coagulation properties. In the follow-up study, we found that
      among the 10 cows with the poorest coagulating properties, 4 cows consistently
      produced poorly coagulating (PC) or NC milk, corresponding to a frequency of 7%.
      Noncoagulating milk was defined as milk that failed to form a coagulum, defined
      as increase in the storage modulus (G') in oscillatory rheometry, within 45min
      after addition of chymosin. Poorly coagulating milk was characterized by forming
      a weak coagulum of low G'. Milk proteomic profiling and contents of different
      casein variants, ionic contents of Ca, P and Mg, kappa-casein (CN) genotypes,
      casein micelle size, and coagulation properties of the 4 NC or PC samples were
      compared with milk samples of 4 cows producing milk with good coagulation
      properties. The studies included determination of production of
      caseinomacropeptide to ascertain whether noncoagulation could be ascribed to the
      first or second phase of chymosin-induced coagulation. Caseinomacropeptide was
      formed in all 8 milk samples after addition of chymosin, indicating that the
      first step (cleavage of kappa-CN) was not the cause of inability to coagulate.
      Furthermore, the effect of mixing noncoagulating and well-coagulating milk was
      studied. By gradually blending NC with well-coagulating milk, the coagulation
      properties of the well-coagulating samples were compromised in a manner similar
      to titration. Milk samples from cows that consistently produced NC milk were
      further studied at the udder quarter level. The coagulation properties of the
      quarter milk samples were not significantly different from those of the composite
      milk sample, showing that poor coagulation traits and noncoagulation traits of
      the composite milk were not caused by the milk quality of a single quarter. The
      milk samples exhibiting PC or NC properties were all of the kappa-CN variant AA
      genotype, and contained casein micelles with a larger mean diameter and a lower
      fraction of kappa-CN relative to total CN than milk with good coagulation
      properties. Interestingly, the relative proportions of different phosphorylation
      forms of alpha-CN differed between well-coagulating milk and PC or NC milk
      samples. The PC and NC milk samples contained a lower proportion of the 2 less
      phosphorylated variants of alpha-CN (alpha(S1)-CN-8P and alpha(S2)-CN-11P)
      compared with samples of milk that coagulated well.

PMID- 21943731
TI  - Development of a rapid method for the measurement of lactose in milk using a
      blood glucose biosensor.
AB  - Current methods for lactose measurement in dairy products are time consuming and
      tedious and may require expensive equipment and skilled technicians. The aim of
      this research was to develop a novel and rapid method for the routine measurement
      of lactose in dairy products. The proposed method is based on the rapid
      hydrolysis of lactose using beta-galactosidase and subsequently measuring glucose
      using a blood glucose meter. Blood glucose meters were developed after decades of
      research and clinical trials and are used extensively worldwide by individuals
      with diabetes to monitor their blood glucose levels. The method was developed and
      validated in a series of experiments. In the first experiment, temperature and
      time required for the near-complete hydrolysis of lactose were determined.
      Subsequently, the influence of glucose meters and their test strip lots were
      evaluated. We found that meters were not significantly different. However, the
      test strip lots were significantly different from each other. In the second
      experiment, the proposed method was validated using different concentrations of
      lactose solutions (1.9-6.5%) and compared with a HPLC-based reference method. In
      the third experiment, the proposed method was used to determine the lactose
      content of raw milk. The proposed method shows potential for rapid, routine, and
      low-cost measurement of lactose in milk and other dairy products.

PMID- 21943732
TI  - Determination of 10-hydroxystearic, 10-ketostearic, 8-hydroxypalmitic, and 8
      ketopalmitic acids in milk fat by solid-phase extraction plus gas chromatography
      mass spectrometry.
AB  - Fatty acids (FA) bearing oxygenated functions and present in esterified form in
      triacylglycerols are widespread in nature but very little is known about their
      occurrence in dairy products. A method based on gas chromatography (with flame
      ionization detector and mass spectrometry detectors), including the previous
      isolation of polar FA methyl esters by solid-phase extraction, was applied to
      quantify oxygenated FA in milk fat. Samples obtained from ewes and goats fed with
      a variety of oil sources were studied. Fatty acids identified were 8
      ketopalmitic, 8-hydroxypalmitic, 10-ketostearic, and mainly 10-hydroxystearic
      acids. The highest levels of 10-ketostearic acid were obtained in milk from
      animals fed olive oil (up to 1.5%) and from those fed long-chain n-3 FA-enriched
      diets (0.5-1.0%). In all samples, 10-hydroxystearic acid, not reported so far in
      milk, was the second most abundant oxygenated FA (up to 0.8%). The high
      correlation obtained between contents of 10-ketostearic and 10-hydroxystearic
      acids would confirm the existence of a common pathway of formation in the rumen,
      whereas the presence of 8-ketopalmitate and 8-hydroxypalmitate could be
      putatively attributed to mechanisms of beta-oxidation in the tissues. The
      influence of cis-9 C18:1 and trans-10 C18:1 as precursors of these compounds in
      milk and the metabolic pathways involved in their formation are discussed.

PMID- 21943733
TI  - Electroporation enhances the ability of lactobacilli to remove cholesterol.
AB  - The objective of the present study was to evaluate the effect of electroporation
      on the membrane properties of lactobacilli and their ability to remove
      cholesterol in vitro. The growth of lactobacilli cells treated at 7.5 kV/cm for 4
      ms was increased by 0.89 to 1.96 log(10) cfu/mL upon fermentation at 37  degrees
      C for 20 h, the increase being attributed to the reversible and transient
      formation of pores and defragmentation of clumped cells. In addition, an increase
      of cholesterol assimilation as high as 127.2% was observed for most cells
      electroporated at a field strength of 7.5 kV/cm for 3.5 ms compared with a lower
      field strength of 2.5 kV/cm. Electroporation also increased the incorporation of
      cholesterol into the cellular membrane, as shown by an increased
      cholesterol:phospholipids ratio (50.0-59.6%) upon treatment at 7.5 kV/cm compared
      with treatment at 2.5 kV/cm. Saturation of cholesterol was observed in different
      regions of the membrane bilayer such as upper phospholipids, apolar tail, and
      polar heads, as indicated by fluorescence anisotropy using 3 fluorescent probes.
      Electroporation could be a useful technique to increase the ability of
      lactobacilli to remove cholesterol for possible use as cholesterol-lowering
      adjuncts in the future.

PMID- 21943734
TI  - The role of copper in the manufacture of Finnish Emmental cheese.
AB  - The effects of added copper in the manufacture of Finnish Emmental cheese were
      studied. Consequently, cheeses were produced with or without the copper
      supplement and a facultative heterofermentative strain, Lactobacillus rhamnosus
      Lc705, which is currently utilized as a protective culture in large-scale
      manufacture in Finland. Cheeses were examined at 1, 7, 30, 60, and 90 d from the
      microbiological, chemical, and sensory points of view. Organic acid production
      was affected by the presence of copper in the cheeses. The addition of copper to
      cheesemilk increased the level of primary proteolysis and slowed secondary
      proteolysis as measured by nitrogen content in different extracts after citrate
      fractionation of cheeses, in pH 4.4-soluble nitrogen and 5% phosphotungstic acid
      soluble nitrogen, respectively. The presence of copper appears to positively
      regulate the sensory characteristics of the cheese produced in our conditions; in
      particular, consistency was affected significantly. The role of the Lb. rhamnosus
      Lc705 protective strain has not been shown to have important effects on most of
      the parameters that influence the final quality of the cheeses. Although the
      traditional plating systems for revealing bacterial populations during cheese
      manufacture did not reveal any drastic differences caused by the presence of
      copper, the results from chemical and sensory analyses suggest that its use plays
      a significant role in the regulation of bacterial physiological and biochemical
      activities, which in turn affect the sensory quality of Emmental cheese.

PMID- 21943735
TI  - Effect of sodium gluconate on the solubility of calcium lactate.
AB  - Calcium and lactate are present in excess of their solubility in Cheddar cheese.
      Consequently, calcium lactate crystals (CLC) are a common defect in Cheddar
      cheese. A novel approach for preventing CLC is the addition of sodium gluconate.
      Sodium gluconate has the potential to increase the solubility of calcium and
      lactate by forming soluble complexes with calcium and lactate ions, and
      preventing them from being available for the formation of CLC. The objective of
      this study was to determine if sodium gluconate could increase the solubility of
      calcium lactate (CaL(2)). Seven CaL(2) solutions (5.31% wt/wt) with 7 levels of
      sodium gluconate (0, 0.5, 1, 1.5, 2, 3, and 4% wt/wt) were made in triplicate.
      Solutions were stored at 7  degrees C for 21 d, and were visually inspected for
      CLC formation. Subsequently, they were filtered to remove CLC and the supernatant
      was analyzed for lactic acid and gluconic acid by HPLC and for calcium by atomic
      absorption spectroscopy. The visual inspection demonstrated that CLC were formed
      in the solution with 0% gluconate after the first day of storage and CLC
      continued to accumulate over time. A minute amount of CLC was also visible in the
      solution with 0.5% gluconate after 21 d of storage, whereas CLC were not visible
      in the other solutions. The HPLC results indicated a higher concentration of
      calcium and lactic acid in the filtrate from the solutions containing added
      gluconate. Thus, sodium gluconate can increase the solubility of CaL(2).

PMID- 21943736
TI  - Short communication: Preliminary investigation into the effect of freezing and a
      cryopreservant on the recovery of mastitis pathogens from ewe milk.
AB  - The objective of this study was to investigate the recovery of bacteria from ewe
      milk after freezing for 4 or 8 wk with and without the addition of glycerol as a
      cryopreservant. A total of 50 udder-half milk samples with a known range of
      bacterial species were selected, stored, and analyzed in 5 treatment groups: time
      zero; frozen for 4 wk with, and without, glycerol; and frozen for 8 wk with, and
      without, glycerol. A lower recovery was observed in all bacterial species studied
      after freezing. Samples containing fewer than 100 cfu/mL came from ewes with a
      lower somatic cell count and were more likely to be bacteriologically negative
      after freezing than those above this threshold. The addition of glycerol
      increased recovery of gram-negative bacteria after freezing, although this
      requires further study to draw strong conclusions. The effects on gram-positive
      species were inconsistent. We conclude that although the addition of glycerol had
      a small beneficial effect on the sensitivity of detection of bacteria from frozen
      sheep milk, sensitivity was highest in cultures from fresh milk.

PMID- 21943737
TI  - Flexible and fixed partitions in freestalls--effects on lying behavior and cow
      preference.
AB  - The objective was to investigate the effect of stall partition design on total
      lying time, lying position, and stall cleanliness, and to evaluate the
      preferences of cows regarding stalls with traditional fixed stall dividers or
      flexible stall dividers. Using a crossover design, 16 nonlactating dairy cows
      were housed singly for 9 d in pens with 2 freestalls, 1 with fixed cantilever
      dividers and 1 with flexible dividers. The cows were first given access to one
      stall type, and then to the other type of stall, and finally to both in a
      preference test. Type of stall divider did not influence lying behavior (13.5h
      for fixed versus 14.0 h for flexible, +/- 0.4h), lying positions, or stall
      cleanliness; however, the cows showed a preference for lying in the flexible
      stalls (65.2 for flexible vs. 34.8 for fixed +/- 8.2%). This indicated that cows
      are able to distinguish between type of stall divider and that it is important to
      them; however, it is not clear if the reason for this is the shape or the
      properties of the dividers. We concluded that cattle chose a flexible stall
      divider over a fixed one, but the long-term consequences of this preference are
      not clear, because no obvious changes in stall usage were observed when cows were
      only given access to one type of divider.

PMID- 21943738
TI  - The effect of recurrent episodes of clinical mastitis caused by gram-positive and
      gram-negative bacteria and other organisms on mortality and culling in Holstein
      dairy cows.
AB  - The objective of this study was to estimate the effects of recurrent episodes of
      different types of clinical mastitis (CM) caused by gram-positive (Streptococcus
      spp., Staphylococcus aureus, Staphylococcus spp.) and gram-negative (Escherichia
      coli, Klebsiella, Citrobacter, Enterobacter, Pseudomonas) bacteria, and other
      organisms (Arcanobacterium pyogenes, Mycoplasma, Corynebacterium bovis, yeast,
      miscellaneous) on the probability of mortality and culling in Holstein dairy
      cows. Data from 30,233 lactations in cows of 7 dairy farms in New York State were
      analyzed. Cows were followed for the first 10 mo in lactation, or until death or
      culling occurred, or until the end of our study period. Generalized linear mixed
      models with a Poisson error distribution were used to study the effects of
      recurrent cases of the different types of CM and several other factors (herd,
      parity, month of lactation, current year and season, profitability, net
      replacement cost, other diseases) on cows' probability of death (model 1) or
      being culled (model 2). Primiparous and multiparous cows were modeled separately
      because they had different risks of mortality and culling and potentially
      different CM effects on mortality and culling. Approximately 30% of multiparous
      cows had at least one case of CM in lactation compared with 16.6% of primiparous
      cows. Multipara also had higher lactational incidence risks of second (10.7%) and
      third (4.4%) cases than primipara (3.7% and 1.1%, respectively). For primipara,
      CM increased the probability of death, with each successive case occurring in a
      month being increasingly lethal. In multipara, gram-negative CM increased the
      probability of death, especially when the gram-negative case was the first or
      second CM case in lactation. Primiparous cows with CM were more likely to be
      culled after CM than if they did not have CM, particularly after a second or
      third case. In multipara, any type of CM increased the probability of being
      culled. Gram-negative CM cases were associated with the numerically highest risk
      of culling.

PMID- 21943739
TI  - A study on cow comfort and risk for lameness and mastitis in relation to
      different types of bedding materials.
AB  - The aim was to obtain data regarding the effects of 4 freestall bedding materials
      (i.e., box compost, sand, horse manure, and foam mattresses) on cow comfort and
      risks for lameness and mastitis. The comfort of freestalls was measured by
      analyzing the way cows entered the stalls, the duration and smoothness of the
      descent movement, and the duration of the lying bout. The cleanliness of the cows
      was evaluated on 3 different body parts: (1) udder, (2) flank, and (3) lower rear
      legs, and the bacteriological counts of the bedding materials were determined.
      The combination of the cleanliness of the cows and the bacteriological count of
      the bedding material provided an estimate of the risk to which dairy cows are
      exposed in terms of intramammary infections. The results of the hock assessment
      revealed that the percentage of cows with healthy hocks was lower (20.5 +/- 6.7),
      the percentage of cows with both damaged and swollen hocks was higher (26.8 +/-
      3.2), and the severity of the damaged hock was higher (2.32 +/- 0.17) on farms
      using foam mattresses compared with deep litter materials [i.e., box compost
      (64.0 +/- 10.4, 3.5 +/- 4.7, 1.85 +/- 0.23, respectively), sand (54.6 +/- 8.2,
      2.0 +/- 2.8, 1.91 +/- 0.09, respectively), and horse manure (54.6 +/- 4.5, 5.5 +/
      5.4, 1.85 +/- 0.17, respectively)]. In addition, cows needed more time to lie
      down (140.2 +/- 84.2s) on farms using foam mattresses compared with the deep
      litter materials sand and horse manure (sand: 50.1 +/- 31.6s, horse manure: 32.9
      +/- 0.8s). Furthermore, the duration of the lying bout was shorter (47.9 +/- 7.4
      min) on farms using foam mattresses compared to sand (92.0 +/- 12.9 min). These
      results indicate that deep litter materials provide a more comfortable lying
      surface compared with foam mattresses. The 3 deep litter bedding materials
      differed in relation to each other in terms of comfort and their estimate of risk
      to which cows were exposed in terms of intramammary infections [box compost: 17.8
      cfu (1.0(4)) +/- 19.4/g; sand: 1.2 cfu (1.0(4)) +/- 1.6/g; horse manure: 110.5
      cfu (1.0(4)) +/- 86.3/g]. Box compost had a low gram-negative bacterial count
      compared with horse manure, and was associated with less hock injury compared
      with foam mattresses, but did not improve lying behavior (lying descent duration:
      75.6 +/- 38.8s, lying bout duration: 46.1 +/- 18.5 min). Overall, sand provided
      the best results, with a comfortable lying surface and a low bacterial count.

PMID- 21943740
TI  - When and where do dairy cows defecate and urinate?
AB  - The accumulation of urine and feces can be responsible for many cow and
      environmental problems. Despite this, little is known about the factors affecting
      defecation and urination. In the first experiment, the occurrence of defecation
      and urination behaviors of 48 lactating Holstein cows was observed [days in milk
      (DIM) = 144.7 +/- 38.0 d, body weight (BW) = 667.1 +/- 72.0 kg, parity = 2.8 +/-
      2.3] in freestalls over 48 h. In the second experiment, defecation and urination
      by 29 lactating Holstein dairy cows were observed (DIM = 62 +/- 22.1 d, BW = 590
      +/- 70.0 kg, parity = 2 +/- 1.3) in another freestall barn over a period of 5 d
      and related to cow activity and feeding behavior. In both experiments, based on
      total occurrence of eliminative behaviors, cows mainly defecated (experiment 1:
      33.4 +/- 2.0%; experiment 2: 42.3 +/- 3.1%) and urinated (experiment 1: 28.2 +/-
      2.5%; experiment 2: 42.7 +/- 4.0%) in the feed alley and while occupying a stall
      (defecation: experiment 1: 28.5 +/- 1.0%; experiment 2: 26.2 +/- 3.0%; urination:
      experiment 1: 42.2 +/- 1.5%; experiment 2: 39.9 +/- 3.8%). Occupying a stall
      included lying, standing in the stall, or standing with 2 feet in the stall and 2
      feet in the alley. In both experiments, differences were found between cows in
      frequency of defecation (experiment 1: 9.8 +/- 4.2/d, range = 3 to 20; experiment
      2: 15.4 +/- 4.3/d, range = 6 to 36) and in frequency of urination (experiment 1:
      7.0 +/- 3.1/d, range = 2 to 18; experiment 2: 9.3 +/- 2.8/d, range = 3 to 19).
      Large differences between cows were observed in the frequency of defecation and
      urination, but these were not correlated with parity, milk production, BW, DIM,
      or dry matter intake.

PMID- 21943741
TI  - The association of serum metabolites with clinical disease during the transition
      period.
AB  - The objective of this observational field study was to validate the relationship
      of serum concentrations of nonesterified fatty acids (NEFA), beta-hydroxybutyrate
      (BHBA), and calcium with disease in early lactation across different management
      systems. Fifty-five Holstein freestall dairy herds located across the United
      States and Canada were selected and visited weekly for blood sample collection
      from 2,365 cows. Only diseases that were consistently recorded across herds and
      blood samples collected before the disease occurred were considered. Metabolite
      concentrations in serum in wk -1 relative to calving were considered as
      predictors of retained placenta (RP) and metritis, and metabolite concentrations
      in serum in wk -1 and wk +1 relative to calving were considered as predictors of
      displaced abomasum (DA). For each disease, each metabolite, and week of sampling
      in the case of DA, a critical threshold was calculated based on the highest
      combined sensitivity and specificity and used to categorize the serum
      concentrations into high and low risk categories. Multivariable logistic
      regression models were built for each disease of interest and week of sampling,
      considering cow as the experimental unit and herd as a random effect. Cows with
      precalving serum NEFA concentrations >= 0.3 mEq/L were more likely to develop RP
      [odds ratio (OR) = 1.8; 95% confidence interval (CI) = 1.3 to 2.6] and metritis
      (OR = 1.8; 95% CI = 1.5 to 2.9) after calving than cows with lower NEFA
      concentrations. Precalving NEFA >= 0.5 mEq/L (OR = 2.4; 95% CI = 1.5 to 3.7),
      postcalving NEFA >= 1.0 mEq/L (OR = 2.7; 95% CI = 1.7 to 4.4), and postcalving
      calcium <= 2.2 mmol/L (OR = 3.1; 95% CI = 1.9 to 5.0) were associated with
      subsequent risk of DA. In conclusion, elevated serum NEFA concentrations within 1
      wk before calving were associated with increased risk of RP, metritis, and DA
      after calving. Serum NEFA and calcium concentrations in the 2 wk around calving
      in combination were associated with the risk of DA.

PMID- 21943742
TI  - First report about the mode of action of combined butafosfan and cyanocobalamin
      on hepatic metabolism in nonketotic early lactating cows.
AB  - The primary aim was to investigate the effect of combined butafosfan and
      cyanocobalamin on liver metabolism in early lactating cows through mRNA
      expression measurements of genes encoding 31 enzymes and transport proteins of
      major metabolic processes in the liver using 16 multiparous early lactating dairy
      cows. The treatments included i.v. injection of 10 mL/100 kg of body weight
      combined butafosfan and cyanocobalamin (TG, n = 8) on 3 d consecutively at 25 +/-
      3 d in milk or injection with physiological saline solution similarly applied
      (CG, n = 8). Results include a higher daily milk production for TG cows (41.1 +/-
      0.9 kg, mean +/- SEM) compared with CG cows (39.5 +/- 0.7 kg). In plasma, the
      concentration of inorganic phosphorus was lower in the TG cows (1.25 +/- 0.08
      mmol/L) after the treatment than in the CG cows (1.33 +/- 0.07 mmol/L). The
      plasma beta-hydroxybutyrate concentration was 0.65 +/- 0.13 mmol/L for all cows
      before the treatment, and remained unaffected post treatment. The unique result
      was that in the liver, the mRNA abundance of acyl-coenzyme A synthetase long
      chain family member 1, involved in fatty acid oxidation and biosynthesis, was
      lower across time points after the treatment for TG compared with CG cows (17.5
      +/- 0.15 versus 18.1 +/- 0.24 cycle threshold, log(2), respectively). In
      conclusion, certain effects of combined butafosfan and cyanocobalamin were
      observed on mRNA abundance of a gene in the liver of nonketotic early lactating
      cows.

PMID- 21943743
TI  - Neither bovine somatotropin nor growth hormone-releasing factor alters expression
      of thyroid hormone receptors in liver and mammary tissues.
AB  - Physiological effects of thyroid hormones are mediated primarily by binding of
      triiodothyronine to specific nuclear receptors. Organ-specific changes in
      production of triiodothyronine from its prohormone, thyroxine, have been
      hypothesized to target the action of thyroid hormones on the mammary gland and
      play a role in mediating or augmenting a galactopoietic response to bovine
      somatotropin (bST). Additionally, tissue responsiveness to thyroid hormones may
      be altered by changes in the number or affinity of nuclear receptors for thyroid
      hormones. In the present study, effects of bST and bovine growth hormone
      releasing factor (bGRF) on thyroid hormone receptors in liver and mammary gland
      were studied. Lactating Holstein cows received continuous infusions of bST or
      bGRF for 63 d or served as uninfused controls. Nuclei were isolated from
      harvested mammary and liver tissues and incubated with [(125)I]-triiodothyronine.
      Treatments did not alter the capacity or affinity of specific binding sites for
      triiodothyronine in liver or mammary nuclei. Evaluation of transcript abundance
      for thyroid hormone receptors showed that isoforms of thyroid hormone receptor or
      retinoid receptor (which may influence thyroid receptor action) expressed in the
      mammary gland were not altered by bST or bGRF treatment. Data do not support the
      hypothesis that administration of bST or bGRF alters sensitivity of mammary
      tissue by changing expression of thyroid hormone receptors.

PMID- 21943744
TI  - Effect of dry period management on mammary gland function and its endocrine
      regulation in dairy cows.
AB  - The objective of this study was to evaluate the effect of shortening the dry
      period on the mammary gland and the hormonal regulation of its functions.
      Holstein cows (n = 18) were assigned to a short dry period (SDP; 35 d; n = 9) or
      a conventional dry period (CDP; 65 d; n = 9). All cows were fed the same diets,
      with the exception that, during the dry period, the SDP cows received only the
      pre-calving diet for 35 d, whereas the CDP cows were fed a high-fiber diet from
      65 to 28 d before calving and then received the same pre-calving diet as the SDP
      cows. Mammary gland functional capacity was evaluated at 70 days in milk, and
      mammary biopsies were taken in early and midlactation. Dry period length averaged
      64.3 +/- 1.1 and 31.9 +/- 1.0 d for the CDP and SDP cows, respectively. The SDP
      cows had a lower milk yield and a lower energy-corrected milk yield compared with
      the CDP cows. The SDP cows also had a lower dry matter intake from wk 5 to 20 of
      lactation and tended to have lower plasma concentrations of beta-hydroxybutyrate
      from wk 1 to 4. Prepartum serum progesterone and estradiol concentrations were
      unaffected by the dry period management. Serum growth hormone concentrations and
      milking-induced prolactin release were similar in both groups. However, during
      the period when the CDP cows were dry but the SDP cows were still being milked
      (wk -9 to -6), serum prolactin concentrations were higher in the SDP cows than in
      the CDP cows. The SDP cows had a lower milk BSA content than the CDP cows after
      the dry period and similar milk lactose concentrations, suggesting that their
      mammary tight junctions were closed following parturition and, therefore, that
      the later stage of their lactogenesis was not impaired by SDP management. In
      early and midlactation, mammary cell apoptosis and proliferation rates as well as
      mammary expression of genes involved in the function of this tissue were
      unaffected by the dry period management strategy. For cows in their second
      lactation, mammary gland functional capacity at 70 d in milk tended to be lower
      in the SDP cows. In conclusion, even though SDP management decreased milk
      production during the subsequent lactation, it did not affect mammary cell
      activity. Although direct evidence is still lacking, decreased mammary cell
      growth during the dry period is likely responsible for this negative effect. The
      higher prolactin concentrations in lactating cows during late gestation could be
      involved in this effect. More research is needed to test these hypotheses.

PMID- 21943745
TI  - Economic feasibility of converting cow manure to electricity: a case study of the
      CVPS Cow Power program in Vermont.
AB  - A case study of the Central Vermont Public Service Corporation (CVPS) Cow Power
      program examines the economic feasibility for dairy farms to convert cow manure
      into electricity via anaerobic methane digestion. The study reviews the mechanism
      for CVPS, dairy farms, electricity customers, and government agencies to develop
      and operate the program since 2004, examines the costs and returns for the
      participating dairy farms, and assesses their cash flow over a period of 7 yr
      under different scenarios. With 6 dairy farms generating about 12 million
      kilowatt-hours of electricity per year and more than 4,600 CVPS electricity
      customers voluntarily paying premiums of $0.04 per kilowatt-hour, or a total of
      about $470,000 per year, the CVPS Cow Power program represents a successful and
      locally sourced renewable energy project with many environmental and economic
      benefits. Factors for the successful development and operation of the program
      include significant grants from government agencies and other organizations,
      strong consumer support, timely adjustments to the basic electricity price paid
      to the farms, and close collaboration among the participating parties. This study
      confirms that it is technically feasible to convert cow manure to electricity on
      farms, but the economic returns depend highly on the base electricity price,
      premium rate, financial supports from government agencies and other
      organizations, and sales of the byproducts of methane generation.

PMID- 21943746
TI  - A simple analytical and experimental procedure for selection of reference genes
      for reverse-transcription quantitative PCR normalization data.
AB  - Variation in cellular activity in a tissue induces changes in RNA concentration,
      which affects the validity of gene mRNA abundance analyzed by reverse
      transcription quantitative PCR (RT-qPCR). A common way of accounting for such
      variation consists of the use of reference genes for normalization. Programs such
      as geNorm may be used to select suitable reference genes, although a large set of
      genes that are not co-regulated must be analyzed to obtain accurate results. The
      objective of this study was to propose an alternative experimental and analytical
      protocol to assess the invariance of reference genes in porcine mammary tissue
      using mammary RNA and DNA concentrations as correction factors. Mammary glands
      were biopsied from 4 sows on d 110 of gestation (prepartum), on d 5 (early) and
      17 (peak) of lactation, and on d 5 after weaning (postweaning). Relative
      expression of 7 potential reference genes, API5, MRPL39, VAPB, ACTB, GAPDH,
      RPS23, and MTG1, and one candidate gene, SLC7A1, was quantified by RT-qPCR using
      a relative standard curve approach. Variation in gene expression levels, measured
      as cycles to threshold at each stage of mammary physiological activity, was
      tested using a linear mixed model fitting RNA and DNA concentrations as
      covariates. Results were compared with those obtained with geNorm analysis, and
      genes selected by each method were used to normalize SLC7A1. Quantified relative
      mRNA abundance of GAPDH and MRPL39 remained unchanged across stages of mammary
      physiological activity after accounting for changes in tissue RNA and DNA
      concentration. In contrast, geNorm analysis selected MTG1, MRPL39, and VAPB as
      the best reference genes. However, when target gene SLC7A1 was normalized with
      genes selected either based on our proposed protocol or by geNorm, fold changes
      in mRNA abundance did not differ. In conclusion, the proposed analytical protocol
      assesses expression invariance of potential reference genes by accounting for
      variation in tissue RNA and DNA concentrations and thus represents an alternative
      method to select suitable reference genes for RT-qPCR analysis.

PMID- 21943747
TI  - An unusual distribution of the niacin receptor in cattle.
AB  - Responses to pharmacological doses of niacin, an agonist for GPR109A (niacin
      receptor), were different in cattle than in humans and rodents. Thus, the tissue
      distribution of GPR109A was investigated in cattle. Samples of tail head fat,
      back fat, perirenal fat, longissimus muscle, and liver were analyzed for
      abundance of GPR109A mRNA by quantitative real-time reverse transcription-PCR and
      for abundance of GPR109A protein by Western blotting. Niacin receptor transcript
      and protein were detected in all tissues analyzed. The mRNA for GPR109A was more
      abundant in liver than in the other tissues sampled (GPR109A:RPS9 mRNA abundance
      = 0.56 in liver compared with 0.06 in longissimus muscle, 0.15 in kidney fat,
      0.11 in back fat, 0.23 in tail head fat; standard error of the mean = 0.028).
      Additionally, mRNA for GPR109A was found (GPR109A:RPS9 mRNA abundance >= 0.004)
      in each of the 5 regions of bovine brain that were analyzed: cerebral cortex,
      cerebellum, thalamus, hypothalamus, and brain stem. Evaluation of liver tissue by
      immunofluorescence suggested that GPR109A was expressed in parenchymal cells and
      not localized exclusively to immune-system cells. Finally, analysis of the
      putative bovine GPR109A sequence verified that AA residues required for binding
      niacin in human GPR109A are conserved, suggesting that the bovine sequence
      identified encodes a functional niacin receptor. The identification of GPR109A in
      bovine liver, muscle, and brain is a novel finding.

PMID- 21943748
TI  - Intermittent parenteral administration of endotoxin triggers metabolic and
      immunological alterations typically associated with displaced abomasum and
      retained placenta in periparturient dairy cows.
AB  - This study sought to investigate the effects of induced intermittent endotoxemia
      on plasma mediators of carbohydrate and lipid metabolism, humoral immunity, and
      clinical health status in periparturient dairy cows. Sixteen pregnant Holstein
      cows were blocked by parity and day of calving, and were randomly allocated to 1
      of 2 different treatment groups. Eight cows were infused intravenously (i.v.)
      with 100mL of sterile saline and served as the control group (CON). The other 8
      cows were infused i.v. with 100mL of sterile saline containing 3 increasing doses
      of lipopolysaccharide (LPS), from Escherichia coli O111:B4, for 3 consecutive
      weeks during the 2 wk before and 1 wk after parturition as follows: (1) 0.01 MUg
      of LPS/kg of body weight (BW) on d -14 and -10; (2) 0.05 MUg of LPS/kg of BW on d
      -7 and -3; and (3) 0.1 MUg of LPS/kg of BW on d 3 and 7 postpartum. Nine blood
      samples were collected during the experimental period (i.e., from -14 to 28 d
      postpartum) and analyzed for calcium, zinc, iron, copper, glucose, lactate, beta
      hydroxybutyrate (BHBA), nonesterified fatty acids (NEFA), cholesterol, insulin,
      cortisol, serum amyloid A (SAA), lipopolysaccharide-binding protein (LBP),
      haptoglobin (Hp), and anti-LPS IgA, IgG, and IgM. Results showed that
      intermittently induced endotoxemia decreased feed intake and milk production and
      triggered alterations in plasma cholesterol, BHBA, Hp, Ca, Cu, and anti-LPS IgG
      and IgM. All of these changes were associated with a greater number of cows
      affected by metabolic disorders such as left displaced abomasum (LDA, 2 from 8
      LPS cows vs. 0 from 8 CON cows) and retained placenta (RP; 4 from 8 LPS cows vs.
      0 from 8 CON cows). In addition, the discriminant analysis differently clustered
      the cow responses within LPS group, each corresponding to LDA, RP, and the cows
      displaying no clinical health problems (LPS-NO). The stepwise selection procedure
      of the best discriminant variables revealed that plasma Ca and anti-LPS IgG, as
      well as glucose and cortisol, were the best discriminating variables for cows
      affected by LDA, whereas NEFA and cholesterol better discriminated for cows
      affected by RP. This analysis also revealed that the cluster of plasma variables
      including plasma Cu, SAA, BHBA, and anti-LPS IgA were the best discrimination for
      the LPS-NO group. In conclusion, our results indicate a role of endotoxemia,
      during the periparturient period, in development of metabolic and immune
      disturbances, as well as in the etiopathology of displaced abomasum and retained
      placenta in dairy cows.

PMID- 21943749
TI  - Reproductive performance of grazing dairy cows following presynchronization and
      resynchronization protocols.
AB  - Objectives were to compare the effect of presynchronization and resynchronization
      methods on fertility responses of grazing dairy cows at first and second
      artificial insemination (AI) and pregnancy rate during the entire breeding
      season. Lactating dairy cows (n = 1,263) in 2 seasonal grazing farms were
      blocked, within farm, by parity, breed and days in milk. Within each block, cows
      were randomly assigned to 1 of 4 treatments arranged as a 2 * 2 factorial with 2
      presynchronization and 2 resynchronization treatments. Cows had their estrous
      cycles presynchronized with either a PGF(2alpha)-based program (Presynch)
      consisting of 2 injections of PGF(2alpha) administered 14 d apart and starting
      the timed AI protocol 11 d later, or with a PGF(2alpha)-GnRH-based
      presynchronization program (G6G) consisting of an injection of PGF(2alpha),
      followed 3 d later by an injection of GnRH and starting the timed AI protocol 6 d
      later. All cows received the first insemination on the same day, which was
      considered study d 0 and also d 0 of the breeding season. All cows received the 5
      d timed AI protocol that consisted of GnRH on d -8, PGF(2alpha) on d -3 and -2,
      and GnRH+timed AI on d 0. Blood was sampled and analyzed for progesterone on d 
      8. On d 12, cows in each presynchronization treatment either remained as
      untreated controls (RCON) or received a controlled internal drug-release (CIDR)
      insert containing progesterone for 7 d (RCIDR). Estrus was observed daily
      starting on d 19 and cows in estrus were inseminated on the same day. On d 35,
      bulls were placed with the cows for an additional 65 d, completing a 100-d
      breeding season. Holstein cows were less likely to have progesterone >= 1 ng/mL
      on d -8, and had less expression of estrus and pregnancy per AI (P/AI), which
      resulted in a slower rate of pregnancy and a smaller proportion of pregnancy at
      the end of the study than did Jersey or crossbred cows. In addition, body
      condition, days in milk, and plasma progesterone concentration at the first GnRH
      injection of the timed AI protocol had marked effects on the reproductive
      performance of lactating grazing dairy cows. A greater proportion of G6G cows had
      progesterone >= 1 ng/mL at the first GnRH injection of the timed AI protocol
      compared with Presynch cows (82.0 vs. 74.3%). Presynchronization treatment did
      not influence P/AI, but cows in G6G had increased risk of pregnancy loss between
      d 30 and 65 after the first AI (12.9 vs. 8.1%). Nevertheless, an interaction
      between presynchronization and ovarian status was observed, and cows initiating
      the timed AI with progesterone >= 1 ng/mL had greater P/AI when previously
      treated with Presynch than G6G. On the other hand, G6G benefited P/AI of cows
      initiating the timed AI with progesterone < 1 ng/mL. Resynchronization with RCIDR
      altered the pattern of return to estrus, but it did not increase the rate of re
      insemination and decreased the proportion of pregnant cows at the end of the 100
      d breeding period (80.6 vs. 84.4%).

PMID- 21943750
TI  - Effects of gonadotropin-releasing hormone at initiation of the 5-d timed
      artificial insemination (AI) program and timing of induction of ovulation
      relative to AI on ovarian dynamics and fertility of dairy heifers.
AB  - Two experiments evaluated the effects of the first GnRH injection of the 5-d
      timed artificial insemination (AI) program on ovarian responses and pregnancy per
      AI (P/AI), and the effect of timing of the final GnRH to induce ovulation
      relative to AI on P/AI. In experiment 1, 605 Holstein heifers were synchronized
      for their second insemination and assigned randomly to receive GnRH on study d 0
      (n = 298) or to remain as untreated controls (n = 307). Ovaries were scanned on
      study d 0 and 5. All heifers received a controlled internal drug-release (CIDR)
      insert containing progesterone on d 0, a single injection of PGF(2alpha) and
      removal of the CIDR on d 5, and GnRH concurrent with timed AI on d 8. Blood was
      analyzed for progesterone at AI. Pregnancy was diagnosed on d 32 and 60 after AI.
      Ovulation on study d 0 was greater for GnRH than control (35.4 vs. 10.6%).
      Presence of a new corpus luteum (CL) at PGF(2alpha) injection was greater for
      GnRH than for control (43.1 vs. 20.8%), although the proportion of heifers with a
      CL at PGF(2alpha) did not differ between treatments and averaged 87.1%.
      Progesterone on the day of AI was greater for GnRH than control (0.50 +/- 0.07
      vs. 0.28 +/- 0.07 ng/mL). The proportion of heifers at AI with progesterone <0.5
      ng/mL was less for GnRH than for control (73.8 vs. 88.2%). The proportion of
      heifers in estrus at AI did not differ between treatments and averaged 66.8%.
      Pregnancy per AI was not affected by treatment at d 32 or 60 (GnRH = 52.5 and
      49.8% vs. control = 54.1 and 50.0%), and pregnancy loss averaged 6.0%. Responses
      to GnRH were not influenced by ovarian status on study d 0. In experiment 2,
      1,295 heifers were synchronized for their first insemination and assigned
      randomly to receive a CIDR on d 0, PGF(2alpha) and removal of the CIDR on d 5,
      and either GnRH 56 h after PGF(2alpha) and AI 16h later (OVS56, n = 644) or GnRH
      concurrent with AI 72 h after PGF(2alpha) (COS72; n = 651). Estrus at AI was
      greater for COS72 than for OVS56 (61.4 vs. 47.5). Treatment did not affect P/AI
      on d 32 in heifers displaying signs of estrus at AI, but COS72 improved P/AI
      compared with OVS56 (55.0 vs. 47.6%) in those not in estrus at AI. Similarly,
      P/AI on d 60 did not differ between treatments for heifers displaying estrus, but
      CO S72 improved P/AI compared with OVS56 (53.0 vs. 44.7%) in those not in estrus
      at AI. Administration of GnRH on the first day of the 5-d timed AI program
      resulted in low ovulation rate and no improvement in P/AI when heifers received a
      single PGF(2alpha) injection 5 d later. Moreover, extending the proestrus by
      delaying the final GnRH from 56 to 72 h concurrent with AI benefited fertility of
      dairy heifers that did not display signs of estrus at insemination following the
      5-d timed AI protocol.

PMID- 21943751
TI  - Effect of exogenous somatotropin in Holstein calves on mammary gland composition
      and proliferation.
AB  - Pubertal mammary gland growth and development are hormonally regulated, but the
      details are poorly understood in calves. Our purpose was to evaluate the effects
      of exogenous growth hormone (GH) on the biochemical composition of the
      prepubertal mammary gland, mRNA expression of selected genes, and histological
      characteristics of the developing parenchyma (PAR). In this experiment, 19 calves
      (7 +/- 4 d of age) were randomly assigned to 1 of 2 treatments: bovine
      somatotropin (bST, 500 mg; n = 10) or placebo (Sal; 0.9% saline; n = 9). Animals
      were treated every 3 wk beginning on d 23. Calves were assigned to an early (65
      d; tissue harvested after 2 treatment injections) or late collection time (107 d;
      tissue harvested after 4 treatment injections). Calves were fed milk replacer and
      calf starter for 8 wk and starter and hay thereafter. Parenchyma and mammary fat
      pad (MFP) from one udder half were harvested for analysis of protein, lipid, and
      DNA. Additional tissues were preserved for histological analysis or snap-frozen
      for quantitative real-time PCR. Somatotropin treatment did not significantly
      alter the mass of PAR or MFP or the general pattern of development of epithelial
      structures. Significant increases were observed in protein/100 kg of body weight
      (BW), total protein, DNA concentration, DNA/100 kg of BW, and total DNA in 107-d
      calves, and a significant treatment by day interaction was observed for DNA and
      lipid concentrations in PAR. In MFP, a significant decrease was observed in
      protein/100 kg of BW in bST-treated calves and in total MFP protein in 65-d
      calves. A treatment by day interaction was found for total protein, DNA, and
      protein/100 kg of BW. In PAR, relative expression of ATPase-binding cassette 3
      and growth hormone receptor were reduced by bST and both were lower in 107-d
      harvest calves. Epithelial cell retention of bromodeoxyuridine (BrdU; possible
      indicator of stem-like cells) was greatest in 65-d bST-treated calves, and a
      significant time of sampling response and treatment * time interaction were
      observed. Expression of the proliferation marker protein Ki67 was numerically
      higher in bST-treated calves but the difference was nonsignificant. Retention of
      the BrdU label was reduced in 107-d calves. Exogenous growth hormone given to
      calves may affect mammary tissue composition and epithelial cell gene expression
      in subtle ways but exogenous supplementation with bST alone is not likely to
      alter overall development patterns or affect the mass of mammary parenchymal
      tissue. Whether such subtle changes have an effect on subsequent development or
      function is unknown.

PMID- 21943753
TI  - The ability of common mastitis-causing pathogens to survive an ensiling period.
AB  - A forage-based study was conducted to examine the ability of enterococci,
      streptococci, and gram-negative bacteria to survive a 3-wk ensiling process.
      Harvested grass and corn forages were each divided into 3 treatment groups
      consisting of 2 commercially available silage inoculants and 1 negative control
      group. Within 24h of harvest, a uniform amount of forage was added to each of 18
      vacuum-sealable freezer bags. Inoculants 1 and 2 were applied to each of 6 bags
      and the remaining 6 bags were not inoculated (negative control). All bags were
      sealed using an industry-grade vacuum sealer to create a pillow pack. At wk 1, 2,
      and 3 of the ensiling process, 6 bags were opened, 2 from each of the 3 groups.
      Dry matter (DM), pH, and bacterial enumeration were determined on the forage
      before ensiling, as well as at wk 1, 2, and 3 of ensiling. The pH of grass and
      corn samples decreased to 5.2 and 4.1, respectively, by the end of the ensiling
      period. Inoculant 2 (7.3 log(10) cfu/g of DM) resulted in a greater enterococcal
      count in grass samples than did inoculant 1 (4.2 log(10) cfu/g of DM) at 3 wk of
      ensiling and both were greater than the negative control (1.2 log(10) cfu/g of
      DM). Counts of streptococci in grass samples at wk 3 were greater in inoculated
      samples (inoculant 1, 7.6 log(10) cfu/g of DM; inoculant 2, 7.0 log(10) cfu/g of
      DM) compared with the negative control (4.3 log(10) cfu/g of DM). Treatment
      differences were observed following 1 wk of ensiling in corn samples.
      Enterococcal counts on corn samples following the 3-wk ensiling were not
      significantly different between inoculant 1 (4.3 log(10) cfu/g of DM) and
      inoculant 2 (4.4 log(10) cfu/g of DM). However, counts in both inoculated groups
      were greater than in the negative control group (4.0 log(10) cfu/g of DM). No
      significant treatment differences were observed for streptococci counts at wk 3.
      Counts for gram-negative bacteria were not detectable by wk 3 of ensiling in
      either grass or corn samples. The addition of a silage inoculant led to greater
      counts of enterococci and streptococci in grass silage compared with the negative
      control at the end of a 3-wk ensiling period. The application of a silage
      inoculant led to increased enterococci counts, but not streptococci counts, in
      corn samples following the ensiling period. These data indicate that enterococci
      and streptococci are able to survive the pH decrease observed during ensiling.

PMID- 21943752
TI  - Temporal changes in plasma concentrations of hormones and metabolites in pasture
      fed dairy cows during extended lactation.
AB  - This experiment measured variations in plasma concentrations of metabolic
      hormones and metabolites in cows undergoing extended lactations of up to 670 d at
      2 planes of nutrition. Thirty-seven Holstein-Friesian cows that calved in late
      winter were selected for varying milk yield and then managed for a lactation of
      670 d by delaying breeding until approximately 450 d in milk (DIM). Cows grazed
      fresh pasture supplemented with pasture silage or hay and crushed wheat or
      triticale grain. Dietary intake was reduced by approximately 1.8 kg (dry matter)
      grain/cow per day for 19 of the cows from 300 DIM until the end of lactation to
      assess the effect of restricted energy intake on the persistency of milk
      production. Samples of blood were collected monthly from each cow to measure
      plasma concentrations of selected hormones and metabolites. Dietary restriction
      beyond 300 DIM reduced yields of milk, protein, and fat, but did not alter the
      proportion of cows reaching the 670-d lactation target. Dietary restriction had
      no effect on cow BW or plasma concentrations of any hormones or metabolites.
      Overall, blood plasma concentrations of insulin-like growth factor-I, leptin, and
      glucose were elevated from 301 to 600 DIM compared with 0 to 300 DIM, whereas
      concentrations of growth hormone and nonesterified fatty acids were lower after
      300 DIM. Plasma concentrations of insulin and prolactin were unaffected by stage
      of lactation, but prolactin concentrations increased during summer. These changes
      were consistent with a decrease in milk yield and an increase in the partitioning
      of nutrients to body tissue gain, primarily adipose tissue, throughout the later
      stages of the extended lactation. Cows that continued milking beyond 600 DIM had
      increased plasma concentrations of growth hormone and decreased concentrations of
      glucose and leptin compared with cows that milked <600 DIM. These differences,
      coupled with reduced body weight gain, indicated an increased priority for
      nutrient partitioning to milk production at the expense of body tissue gain
      throughout the extended lactation period in cows with greater lactation
      persistency.

PMID- 21943754
TI  - Flow cytometric differential cell counts in milk for the evaluation of
      inflammatory reactions in clinically healthy and subclinically infected bovine
      mammary glands.
AB  - Somatic cell counts (SCC) are generally used as an indicator of udder health. In
      Germany, a cutoff value of 100,000 cells/mL is currently used to differentiate
      between healthy and diseased mammary glands. In addition to SCC, differential
      cell counts (DCC) can be applied for a more detailed evaluation of the udder
      health status. The aim of this study was to differentiate immune cells in milk of
      udder quarters classified as healthy based on SCC values of <100,000 cells/mL.
      Twenty cows were selected and 65 healthy udder quarters were compared with a
      control group of 15 diseased udder quarters (SCC>100,000 cells/mL). Cells were
      isolated from milk of all quarters to measure simultaneously percentages of
      lymphocytes, macrophages, and polymorphonuclear neutrophilic leukocytes (PMNL) by
      flow cytometric analysis. The bacteriological status of all 80 quarters was also
      determined. Differential cell count patterns of milk samples (n = 15) with
      extreme low SCC values of <= 6,250 cells/mL revealed high lymphocyte proportions
      of up to 88%. Milk cell populations in samples (n = 42) with SCC values from
      >6,250 to <= 25,000 cells/mL were also dominated by lymphocytes, whereas DCC
      patterns of 6 out of 41 milk samples with SCC values from >= 9,000 to <= 46,000
      cells/mL indicated already inflammatory reactions based on the predominance of
      PMNL (56-75%). In 13 of 15 milk samples of the diseased udder quarters (SCC
      >100,000 cells/mL), PMNL were categorically found as dominant cell population
      with proportions of >= 49%. Macrophages were the second predominant cell
      population in almost all samples tested in relation to lymphocytes and PMNL.
      Further analysis of the data demonstrated significant differences of the cellular
      components between udder quarters infected by major pathogens (e.g.,
      Staphylococcus aureus; n = 5) and culture-negative udder quarters (n = 56). Even
      the percentages of immune cells in milk from quarters infected by minor pathogens
      (e.g., coagulase-negative staphylococci; n = 19) differed significantly from
      those in milk of culture-negative quarters. Our flow cytometric analysis of
      immune cells in milk of udder quarters classified as healthy by SCC <100,000
      cells/mL revealed inflammatory reactions based on DCC.

PMID- 21943755
TI  - Effect of mobility score on milk yield and activity in dairy cattle.
AB  - Previous studies have indicated that lame cows have reduced milk yield both
      before and after they are treated for lameness. One explanation for the reduction
      in yield before treatment is delay to treatment; that is, cows have impaired
      mobility for some time before they are treated. The aim of this study was to test
      this hypothesis by investigating temporal associations between change in milk
      yield and change in mobility score. Mobility score (MS, on a scale from 0 to 3),
      milk yield, treatments for lameness, and cow activity were recorded on 312 cows
      in a dairy herd in Somerset, UK, for 1 yr. The MS was scored every 2 wk and
      compared with daily yield and activity (mean log steps/h) averaged over the
      previous 16 d. Approximately 52% of MS changed within 14 d, usually by 1 unit.
      Overall, milk yields of cows with MS 1 were greater than those of cows with other
      scores. Cows with MS 2 and 3 produced 0.7 (95% confidence interval: 0.35-0.97)
      and 1.6 (0.98-2.23) kg less milk/d, respectively, compared with cows with MS 1.
      In addition, cows with MS 1 were significantly more active than cows with MS 0,
      2, or 3. Cows with MS 2 and 3 were 0.02 (0.01-0.03) and 0.03 (0.01-0.05) mean log
      steps less active than cows with MS 1. Six to 8 wk before nonlame cows became MS
      2 or 3, their daily milk yield decreased by a mean (95% CI) of 0.5 kg (0.12-0.47)
      and 0.9 kg (0.16-1.65) respectively. Daily yield remained lower by 0.42 kg (0.09
      0.75) for 4 wk after cows with MS 2 had recovered. The activity of cows was
      significantly less (0.01 mean log steps) with increasing MS; the associations
      between activity and parity (means 0.03-0.11) and month of lactation (means 0.03
      0.36) were quantitatively larger. Results from a multistate model indicated that
      once cows were lame they remained lame or became lame again despite treatment. In
      conclusion, cows' milk production started to decline before their mobility was
      visibly impaired.

PMID- 21943756
TI  - Validity of prepartum changes in vaginal and rectal temperature to predict
      calving in dairy cows.
AB  - The prevalence of dystocia is high in many dairy herds and is associated with
      stillbirth and negative effects for the cow. An accurate predictor of calving
      would enable supervision of cows more precisely to a relevant time interval so
      that obstetrical assistance can be provided in a timely manner. This might help
      to decrease calf mortality rate. Evidence exists that cows exhibit a decrease in
      body temperature before the onset of calving. The performance of a decrease in
      body temperature as a test to predict the onset of calving in dairy cows has not
      been investigated. The objective was to investigate test criteria of a decrease
      in vaginal and rectal temperature as predictors of calving in dairy cows. In 3
      experiments, temperature loggers (Minilog 8, Vemco Ltd., Halifax, Canada) were
      inserted into the vagina of cows before calving (n = 85), and rectal temperatures
      were measured twice daily in 55 of these cows. Vaginal temperatures were 0.2 to
      0.3  degrees C and 0.6 to 0.7  degrees C lower on the day of calving compared
      with 24 and 48 h before calving, respectively. Rectal temperatures were 0.3 to
      0.5  degrees C and 0.4 to 0.6  degrees C lower on the day of calving compared
      with 24 and 48 h before calving, respectively. Vaginal temperatures exhibited a
      diurnal rhythm during the 120 h before calving, which continued on a lower level
      during the 48 h preceding parturition. In the 3 experiments, a decrease in
      vaginal temperature of >= 0.3  degrees C over 24h could predict calving within
      24h, with sensitivity ranging from 62 to 71% and specificity ranging from 81 to
      87%. Similarly, a decrease in rectal temperature measured at 0730 h of >= 0.3 
      degrees C could predict calving within 24h, with sensitivity from 44 to 69% and
      specificity from 86 to 88%. Although dairy cows exhibit a distinctive decrease in
      vaginal and rectal temperatures commencing approximately 48 h before calving,
      detecting this decrease does not determine the onset of calving precisely.
      Nevertheless, it can provide valuable information in addition to the traditional
      signs (i.e., relaxation of the sacrosciatic ligament) that calving is imminent.

PMID- 21943757
TI  - Short communication: Milk ELISA status for bovine leukosis virus infection is not
      associated with milk production in dairy cows.
AB  - The objective of this study was to assess whether the milk ELISA status for
      antibodies against bovine leukemia virus was associated with 305-d milk
      production in Canadian dairy cattle. Test results and test-day production data
      from 19,785 dairy cows were available for analysis. A linear mixed model was used
      with the estimated 305-d milk production as the outcome and lactation number,
      somatic cell count, calving season, days in milk, and breed as fixed effects.
      Herd nested in province was included as random effect. In conclusion, bovine
      leukemia virus antibody milk ELISA status was not associated with milk
      production.

PMID- 21943758
TI  - Rumen fermentation and production effects of Origanum vulgare L. leaves in
      lactating dairy cows.
AB  - A lactating cow trial was conducted to study the effects of dietary addition of
      oregano leaf material (Origanum vulgare L.; OV; 0, control vs. 500 g/d) on
      ruminal fermentation, methane production, total tract digestibility, manure gas
      emissions, N metabolism, organoleptic characteristics of milk, and dairy cow
      performance. Eight primiparous and multiparous Holstein cows (6 of which were
      ruminally cannulated) were used in a crossover design trial with two 21-d
      periods. Cows were fed once daily. The OV material was top-dressed and mixed with
      a portion of the total mixed ration. Cows averaged 80 +/- 12.5 d in milk at the
      beginning of the trial. Rumen pH, concentration of total and individual volatile
      fatty acids, microbial protein outflow, and microbial profiles were not affected
      by treatment. Ruminal ammonia-N concentration was increased by OV compared with
      the control (5.3 vs. 4.3mM). Rumen methane production, which was measured only
      within 8h after feeding, was decreased by OV. Intake of dry matter (average of
      26.6 +/- 0.83 kg/d) and apparent total tract digestibly of nutrients did not
      differ between treatments. Average milk yield, milk protein, lactose, and milk
      urea nitrogen concentrations were unaffected by treatment. Milk fat content was
      increased and 3.5% fat-corrected milk yield tended to be increased by OV,
      compared with the control (3.29 vs. 3.12% and 42.4 vs. 41.0 kg/d, respectively).
      Fat-corrected (3.5%) milk feed efficiency and milk net energy for lactation
      (NE(L)) efficiency (milk NE(L) / NE(L) intake) were increased by OV compared with
      the control (1.64 vs. 1.54 kg/kg and 68.0 vs. 64.4%, respectively). Milk sensory
      parameters were not affected by treatment. Urinary and fecal N losses, and manure
      ammonia and methane emissions were unaffected by treatment. Under the current
      experimental conditions, supplementation of dairy cow diets with 500 g/d of OV
      increased milk fat concentration, feed and milk NE(L) efficiencies, and tended to
      increase 3.5% fat-corrected milk yield. The sizable decrease in rumen methane
      production with the OV supplementation occurred within 8h after feeding and has
      to be interpreted with caution due to the large within- and between-animal
      variability in methane emission estimates. The OV was introduced into the rumen
      as a pulse dose at the time of feeding, thus most likely having larger effect on
      methane production during the period when methane data were collected. It is
      unlikely that methane production will be affected to the same extent throughout
      the entire feeding cycle.

PMID- 21943759
TI  - Effect of forage source and a supplementary methionine hydroxy analog on nitrogen
      balance in lactating dairy cows offered a low crude protein diet.
AB  - Four primiparous and 4 multiparous midlactation dairy cows were stratified by pre
      experimental milk yield (23.5 +/- 2.3 kg/d), protein yield (0.75 +/- 0.066 kg/d),
      parity, and days in lactation (121 +/- 10 d) into 4 groups of 2 in a 2 * 2
      factorial, Latin square design (n = 8) to assess the effect of forage source and
      a supplementary methionine hydroxy analog on nitrogen (N) balance where low crude
      protein (CP) diets (13.3%) are offered. Diets contained either predominantly
      grass silage [GS (G- and G+)] or corn silage [CS (C- and C+)] as the forage
      source and were offered with (G+ and C+) or without (G- and C-) the isopropyl
      ester of 2-hydroxy-4 methylthio butanoic acid (HMBi). The G- and G+ contained 46%
      GS and 10% CS in the dry matter (DM), whereas C- and C+ contained 12% GS and 52%
      CS in the DM. Supplementary HMBi was included at a rate of 0.2% of DM in G+ and
      C+ diets. Diets were isonitrogenous (9.8 +/- 0.4% protein truly digested in the
      small intestine) and isoenergetic (0.96 +/- 0.01 units of energy for lactation;
      kg/DM). Each of the 4 experimental periods lasted 24 d: 14 d for dietary
      adaptation, followed by 10 d of housing in individual metabolism stalls; N
      balance was conducted on the last 5 d of each experimental period. Intake of DM
      was higher for CS-based vs. GS-based diets (20.23 vs. 18.41 kg/d). No effect of
      dietary treatment was found on milk yield or yields of milk fat, protein, and
      lactose. Supplementing with HMBi tended to improve milk solids yield (1.69 vs.
      1.59 kg/d), casein yield (0.59 vs. 0.55 kg/d), and concentrations of casein (2.89
      vs. 2.73%) and protein (3.58 vs. 3.49%) in the milk. Dietary N intake was higher
      for CS-based vs. GS-based diets (0.460 vs. 0.422 kg/d). However, forage source or
      supplementary HMBi had no effect on N excretion in the feces, urine, or milk.
      Excretion of urinary urea was positively related to N intake. Concentrations of
      urea N in the plasma (2.34 vs. 1.72 mmol/L), milk (2.54 vs. 2.24 mmol/L), and
      urine (123.32 vs. 88.79 mmol/L), and total excretion of urinary urea N (40.23 vs.
      35.09 g/d) were higher for animals offered CS-based vs. GS-based diets. Corn
      silage improved N intake through improved DM intake. However, neither forage
      source nor HMBi supplementation affects N output in the feces, urine, or milk.

PMID- 21943760
TI  - Effects of encapsulated niacin on metabolism and production of periparturient
      dairy cows.
AB  - Nicotinic acid (niacin) can suppress lipolysis, but responses to dietary niacin
      have been inconsistent in cattle. Our aim was to determine if 24 g/d of
      encapsulated niacin (EN; providing 9.6g/d of bioavailable nicotinic acid) alters
      lipid metabolism and productivity of transition cows. Beginning 21 d before
      expected calving, primiparous (n = 9) and multiparous (n = 13) cows (body
      condition score of 3.63 +/- 0.08) were sequentially assigned within parity to EN
      (12 g provided with ration twice daily) or control through 21 d postpartum. Liver
      biopsies were collected on d -21, -4, 1, 7, and 21 relative to parturition. Blood
      samples were collected on d -21, -14, -7, -4, 1, 4, 7, 14, and 21 relative to
      parturition. On d 7 postpartum, a caffeine clearance test was performed to assess
      liver function, and on d 21 to 23 postpartum, blood samples were collected every
      8h to monitor posttreatment nonesterified fatty acid (NEFA) responses. Data were
      analyzed using mixed models with repeated measures over time. A treatment * time
      * parity effect was observed on prepartum dry matter intake (DMI), which was
      caused by a 4 kg/d decrease in DMI of EN-treated multiparous cows compared with
      control multiparous cows during the final 4 d prepartum. A significant increase
      in plasma nicotinamide concentration occurred in EN-treated cows on d -7 and 21
      relative to parturition. Prepartum glucose concentration decreased in treated
      animals, with no difference in plasma insulin concentration. Treatment * time *
      parity effects were detected for NEFA and beta-hydroxybutyrate concentrations
      during the postpartum period. Plasma NEFA peaked at 1,467 +/- 160 MUM for control
      animals compared with 835 +/- 154 MUM for EN-treated animals. After treatments
      ended on d 21, no evidence was found for a plasma NEFA rebound in either parity
      group. A treatment * parity * time interaction was detected for liver
      triglyceride content, indicating a tendency for less liver triglyceride in EN
      treated primiparous cows, but caffeine clearance rates were not affected by
      treatment. No treatment effects were observed for body condition score, body
      weight, energy balance, or milk or milk component production. A high dose of EN
      can decrease postpartum plasma NEFA concentration, but may also decrease
      prepartum DMI.

PMID- 21943761
TI  - Corn silage versus corn silage:alfalfa hay mixtures for dairy cows: effects of
      dietary potassium, calcium, and cation-anion difference.
AB  - Corn silage (CS) has replaced alfalfa hay (AH) and haylage as the major forage
      fed to lactating dairy cows, yet many dairy producers believe that inclusion of
      small amounts of alfalfa hay or haylage improves feed intake and milk production.
      Alfalfa contains greater concentrations of K and Ca than corn silage and has an
      inherently higher dietary cation-anion difference (DCAD). Supplemental dietary
      buffers such as NaHCO(3) and K(2)CO(3) increase DCAD and summaries of studies
      with these buffers showed improved performance in CS-based diets but not in AH
      based diets. We speculated that improvements in performance with AH addition to
      CS-based diets could be due to differences in mineral and DCAD concentrations
      between the 2 forages. The objective of this experiment was to test the effects
      of forage (CS vs. AH) and mineral supplementation on production responses using
      45 lactating Holstein cows during the first 20 wk postpartum. Dietary treatments
      included (1) 50:50 mixture of AH and CS as the forage (AHCS); (2) CS as the sole
      forage; and (3) CS fortified with mineral supplements (CaCO(3) and K(2)CO(3)) to
      match the Ca and K content of the AHCS diet (CS-DCAD). Feed intake and milk
      production were equivalent or greater for cows fed the CS and CS-DCAD diets
      compared with those fed the AHCS diet. Fat percentage was greater in cows fed the
      CS compared with the AHCS diet. Fat-corrected milk (FCM; 3.5%) tended to be
      greater in cows fed the CS and CS-DCAD diets compared with the AHCS diet. Feed
      efficiencies measured as FCM/dry matter intake were 1.76, 1.80, and 1.94 for the
      AHCS, CS, and CS-DCAD diets, respectively. The combined effects of reduced feed
      intake and increased FCM contributed to increased feed efficiency with the CS
      DCAD diet, which contained 1.41% K compared with 1.18% K in the CS diet, and we
      speculate that this might be the result of added dietary K and DCAD effects on
      digestive efficiency. These results indicate no advantage to including AH in CS
      based diets, but suggest that improving mineral supplementation in CS-based diets
      may increase feed efficiency.

PMID- 21943762
TI  - Maturation of endogenous glucose production in preterm and term calves.
AB  - Glucose disposability is often impaired in neonatal calves and even more in
      preterm calves. The objective of this study was to investigate ontogenic
      maturation of endogenous glucose production (eGP) in calves and its effects on
      postnatal glucose homeostasis. Calves (n = 7 per group) were born preterm (PT;
      delivered by section 9 d before term) or at term (T; spontaneous vaginal
      delivery), or spontaneously born and fed colostrum for 4 d (TC). Blood samples
      were taken immediately after birth and before and 2h after feeding at 24h after
      birth (PT; T) or on d 4 of life (TC) to determine metabolic and endocrine
      changes. After birth (PT and T) or on d 3 of life (TC), fasted calves were
      gavaged with deuterium-labeled water to determine gluconeogenesis (GNG) and
      intravenously infused with [U(13)C]-glucose to measure eGP and glucose oxidation
      (GOx) in blood plasma. After slaughter at 26h after birth (PT, T) or on d 4 of
      life (TC), glycogen concentrations in liver and hepatic mRNA concentrations and
      enzyme activities of pyruvate carboxylase, phosphoenolpyruvate carboxykinase
      (PEPCK), and glucose-6-phosphatase were measured. Preterm calves had the lowest
      plasma concentrations of cortisol and 3,5,3'-triiodothyronine at birth. Plasma
      glucose concentrations from d 1 to 2 decreased more, but plasma concentrations of
      lactate and urea and glucagon:insulin ratio were higher in PT than in T and TC
      calves. The eGP, GNG, GOx, as well as hepatic glycogen concentrations and PEPCK
      activities, were lowest in PT calves. Results indicate impaired glucose
      homeostasis due to decreased eGP in PT calves and maturation of eGP with
      ontogenic development.

PMID- 21943763
TI  - Effect of reduced ferulate-mediated lignin/arabinoxylan cross-linking in corn
      silage on feed intake, digestibility, and milk production.
AB  - Cross-linking of lignin to arabinoxylan by ferulates limits in vitro rumen
      digestibility of grass cell walls. The effect of ferulate cross-linking on dry
      matter intake (DMI), milk production, and in vivo digestibility was investigated
      in ad libitum and restricted-intake digestion trials with lambs, and in a dairy
      cow performance trial using the low-ferulate sfe corn mutant. Silages of 5 inbred
      corn lines were fed: W23, 2 W23sfe lines (M04-4 and M04-21), B73, and B73bm3. As
      expected, the W23sfe silages contained fewer ferulate ether cross-links and
      B73bm3 silage had a lower lignin concentration than the respective genetic
      controls. Silages were fed as the sole ingredient to 4 lambs per silage
      treatment. Lambs were confined to metabolism crates and fed ad libitum for a 12-d
      adaptation period followed by a 5-d collection period of feed refusals and feces.
      Immediately following the ad libitum feeding trial, silage offered was limited to
      2% of body weight. After a 2-d adaptation to restricted feeding, feed refusals
      and feces were collected for 5 d. Seventy Holstein cows were blocked by
      lactation, days in milk, body weight, and milk production and assigned to total
      mixed ration diets based on the 5 corn silages. Diets were fed for 28 d and data
      were collected on weekly DMI and milk production and composition. Fecal grab
      samples were collected during the last week of the lactation trial for estimation
      of feed digestibility using acid-insoluble ash as a marker. Silage, total mixed
      ration, feed refusals, and fecal samples were analyzed for crude protein, starch,
      neutral detergent fiber (NDF), cell wall polysaccharides, and lignin. The W23sfe
      silages resulted in lower DMI in the ad libitum trial than the W23 silage, but
      DMI did not differ in the restricted trial. No differences were observed for NDF
      or cell wall polysaccharide digestibility by lambs with restricted feeding, but
      the amount of NDF digested daily increased for lambs fed the M04-21 W23sfe silage
      ad libitum. Lambs were less selective against NDF and lignin when offered W23sfe
      silages. The B73bm3 silage did not affect DMI or digestibility of cell walls at
      the restricted feeding level, but total daily NDF digested was greater at ad
      libitum intake. Intake, milk production, and cell wall digestibility were greater
      for cows fed diets containing W23sfe silages than for those fed W23 silage.
      Although milk production was greater for the B73bm3 diet, DMI and cell wall
      digestibility were not altered. Cows were less selective against cell wall
      material when fed both W23sfe and B73bm3 silages. Reduced ferulate cross-linking
      in sfe corn silage is a new genetic mechanism for improving milk production.

PMID- 21943764
TI  - Ruminal fermentation, milk fatty acid profiles, and productive performance of
      Holstein dairy cows fed 2 different safflower seeds.
AB  - A lactation trial was conducted to determine the effects of supplementing whole
      safflower seeds (SS) on ruminal fermentation, lactational performance, and milk
      fatty acid (FA) profiles. Nine multiparous Holstein cows (days in milk = 110 +/-
      20) were used in a replicated 3 * 3 Latin square design. Each period lasted 21 d,
      with 14 d of adaptation and 7 d of data collection. Within square, cows were
      randomly assigned to a sequence of 3 dietary treatments as follows: cottonseed
      total mixed ration (TMR; CST), conventional SS (variety S-208) TMR (CSST), and
      NutraSaff SS (Safflower Technologies International, Sidney, MT) TMR (NSST). Diets
      contained approximately 63% forage (36% alfalfa hay, 4% grass hay, and 23% corn
      silage) and 37% concentrate supplemented with 2% cottonseed to the CST and 3%
      conventional or NutraSaff SS to the CSST or the NSST, respectively. Intake of dry
      matter (DM) averaged 21.8 kg/d and did not differ across diets, but feeding the
      NSST decreased intake of neutral detergent fiber (NDF) due to lower dietary
      concentration of NDF in the NSST. Digestibilities of DM and nutrients were
      similar among treatments. No differences in yields of milk or milk components
      were observed in response to supplementing SS. Dietary treatments did not affect
      ruminal pH, total or molar proportions of ruminal volatile FA, and ammonia-N.
      However, cows fed SS had a higher molar proportion of isobutyrate than those fed
      the CST diet. Ruminal C16:0 FA concentration increased with the CST, whereas
      C18:1 cis-9 and C18:2 n-6 tended to increase with SS supplementation, indicating
      that conventional and NutraSaff SS were partially protected from microbial
      biohydrogenation. Supplementing SS decreased milk C16:0 concentration, whereas it
      increased C18:1 cis-9 and C18:1 trans-9. Milk FA C18:1 trans-11 and cis-9, trans
      11 conjugated linoleic acid increased and tended to increase with feeding the
      NSST, respectively, but not the CSST diet. In conclusion, supplementing diets
      with whole SS at 3% of dietary DM can be an effective strategy of fat
      supplementation to lactating dairy cows without negative effects on lactational
      performance and milk FA profiles.

PMID- 21943766
TI  - Rates of inbreeding and genetic diversity in Canadian Holstein and Jersey cattle.
AB  - The accumulation of inbreeding and the loss of genetic diversity is a potential
      problem in the modern dairy cattle breeds. Therefore, the purpose of this study
      was to analyze the pedigrees of Canadian Holstein and Jersey cattle to estimate
      the past and current rates of inbreeding and genetic diversity, and to identify
      the main causes of diversity loss. Completeness and depth of the pedigrees were
      good for both breeds. For Holsteins, the average rates of inbreeding per
      generation showed a decreasing trend in recent years when compared with the
      1990s. The estimated current effective population size was about 115 for
      Holsteins and is not expected to significantly change in the near future if
      generation intervals stay at current value, as rates of increase in inbreeding
      and coancestry showed decreasing trends. For Jerseys, the estimated effective
      population size was about 55 and it is expected to decrease in the near future
      due to the observed increasing rates of coancestry and inbreeding. Ancestors with
      the highest marginal genetic contributions to the gene pool in current years and
      with the highest contributions to inbreeding were identified. The 2 most heavily
      used and represented ancestors in the Holstein pedigree (i.e., Round Oak Rag
      Apple Elevation and his son Hanoverhill Starbuck), accounted for 30% of
      inbreeding. Analyses revealed that the most important cause of genetic diversity
      loss in both breeds was genetic drift accumulated over nonfounder generations,
      which occurred due to small effective population size. Therefore, a need exists
      in both breeds, particularly in Jerseys, for managing selection and mating
      decisions to control future coancestry and inbreeding, which would lead to better
      handling of the effective population size.

PMID- 21943765
TI  - Molecular basis of structural makeup of hulless barley in relation to rumen
      degradation kinetics and intestinal availability in dairy cattle: A novel
      approach.
AB  - To date, no study has been done of molecular structures in relation to nutrient
      degradation kinetics and intestinal availability in dairy cattle. The objectives
      of this study were to (1) reveal molecular structures of hulless barley affected
      by structural alteration using molecular spectroscopy (diffuse reflectance
      infrared Fourier transform) as a novel approach, and (2) quantify structure
      features on a molecular basis in relation to digestive kinetics and nutritive
      value in the rumen and intestine in cattle. The modeled feeds in this study were
      4 types of hulless barley (HB) cultivars modified in starch traits: (a) normal
      starch cultivar, (b) zero-amylose waxy, (c) waxy, and (d) high-amylose. The
      molecular structural features were determined using diffuse reflectance infrared
      Fourier transform spectroscopy in the mid-infrared region (ca. 4,000-800 cm(-1))
      of the electromagnetic spectrum. The items assessed included infrared intensity
      attributed to protein amide I (ca. 1,715-1,575 cm(-1)), amide II (ca. 1,575-1,490
      cm(-1)), alpha-helix (ca. 1,648-1,660 cm(-1)), beta-sheet (ca. 1,625-1,640 cm(
      1)), and their ratio, beta-glucan (ca. 1,445-1,400 cm(-1)), total carbohydrates
      (CHO; ca. 1,188-820 cm(-1)) and their 3 major peaks, structural carbohydrates
      (ca. 1,277-1,190 cm(-1)), and ratios of amide I to II and amide I to CHO. The
      results show that (1) the zero-amylose waxy was the greatest in amide I and II
      peak areas, as well as in the ratio of protein amide I to CHO among HB; (2) alpha
      helix-to-beta-sheet ratio differed among HB: the high-amylose was the greatest,
      the zero-amylose waxy and waxy were the intermediate, and the normal starch was
      the lowest; (3) HB were similar in beta-glucan and CHO molecular structural
      makeup; (4) altered starch HB cultivars were similar to each other, but were
      different from the normal starch cultivar in protein molecular makeup; and (5)
      the rate and extent of rumen degradation of starch and protein were highly
      related to the molecular structural makeup of HB. In conclusion, the molecular
      structural makeup on a molecular basis was related to rumen degradation kinetics
      and intestinal availability in dairy cattle. The alteration of starch structure
      in barley grain affects starch structure and the magnitude of protein and beta
      glucan contents, as well as the protein molecular structure of HB.

PMID- 21943767
TI  - Genetic parameters for female fertility, locomotion, body condition score, and
      linear type traits in Czech Holstein cattle.
AB  - The aim of this study was to estimate genetic parameters for fertility traits and
      linear type traits in the Czech Holstein dairy cattle population. Phenotypic data
      regarding 12 linear type traits, measured in first lactation, and 3 fertility
      traits, measured in each of first and second lactation, were collected from 2005
      to 2009 in the progeny testing program of the Czech-Moravian Breeders
      Corporation. The number of animals for each linear type trait was 59,467, except
      for locomotion, where 53,436 animals were recorded. The 3-generation pedigree
      file included 164,125 animals. (Co)variance components were estimated using AI
      REML in a series of bivariate analyses, which were implemented via the DMU
      package. Fertility traits included days from calving to first service (CF1), days
      open (DO1), and days from first to last service (FL1) in first lactation, and
      days from calving to first service (CF2), days open (DO2), and days from first to
      last service (FL2) in second lactation. The number of animals with fertility data
      varied between traits and ranged from 18,915 to 58,686. All heritability
      estimates for reproduction traits were low, ranging from 0.02 to 0.04.
      Heritability estimates for linear type traits ranged from 0.03 for locomotion to
      0.39 for stature. Estimated genetic correlations between fertility traits and
      linear type traits were generally neutral or positive, whereas genetic
      correlations between body condition score and CF1, DO1, FL1, CF2 and DO2 were
      mostly negative, with the greatest correlation between BCS and CF2 (-0.51).
      Genetic correlations with locomotion were greatest for CF1 and CF2 (-0.34 for
      both). Results of this study show that cows that are genetically extreme for
      angularity, stature, and body depth tend to perform poorly for fertility traits.
      At the same time, cows that are genetically predisposed for low body condition
      score or high locomotion score are generally inferior in fertility.

PMID- 21943768
TI  - Genetic analysis of detailed milk protein composition and coagulation properties
      in Simmental cattle.
AB  - The objective of this study was to estimate genetic parameters for milk protein
      fraction contents, milk protein composition, and milk coagulation properties
      (MCP). Contents of alpha(S1)-, alpha(S2)-, beta-, gamma-, and kappa-casein (CN),
      beta-lactoglobulin (beta-LG), and alpha-lactalbumin (alpha-LA) were measured by
      reversed-phase HPLC in individual milk samples of 2,167 Simmental cows. Milk
      protein composition was measured as percentage of each CN fraction in CN
      (alpha(S1)-CN%, alpha(S2)-CN%, beta-CN%, gamma-CN%, and kappa-CN%) and as
      percentage of beta-LG in whey protein (beta-LG%). Rennet clotting time (RCT) and
      curd firmness (a(30)) were measured by a computerized renneting meter.
      Heritabilities for contents of milk proteins ranged from 0.11 (alpha-LA) to 0.52
      (kappa-CN). Heritabilities for alpha(S1)-CN%, kappa-CN%, and beta-CN% were
      similar and ranged from 0.63 to 0.69, whereas heritability of alpha(S2)-CN%,
      gamma-CN%, and beta-LG% were 0.28, 0.18, and 0.34, respectively. Effects of CSN2
      CSN3 haplotype and BLG genotype accounted for more than 80% of the genetic
      variance of alpha(S1)-CN%, beta-CN%, and kappa-CN% and 50% of the genetic
      variance of beta-LG%. The genetic correlations among the contents of CN fractions
      and between CN and whey protein fractions contents were generally low. When the
      data were adjusted for milk protein gene effects, the magnitude of the genetic
      correlations among the contents of milk protein fractions markedly increased,
      indicating that they undergo a common regulation. The proportion of beta-CN in CN
      correlated negatively with kappa-CN% (r=-0.44). The genetic relationships between
      CN and whey protein composition were trivial. Low milk pH correlated with
      favorable MCP. Genetically, contents and proportions of alpha(S1)- and alpha(S2)
      CN in CN were positively correlated with RCT. The relative proportion of beta-CN
      in CN exhibited a genetic correlation with RCT of -0.26. Both the content and the
      relative proportion of kappa-CN in CN did not correlate with RCT. Weak curds were
      genetically associated with increased proportions in CN of alpha(S1)- and
      alpha(S2)-CN, decreased contents of beta-CN and kappa-CN, and decreased
      proportion of kappa-CN in CN. Negligible effects on the estimated correlations
      between a(30) and kappa-CN contents or proportion in CN were observed when the
      model accounted for milk protein gene effects. Increasing beta-CN and kappa-CN
      contents and relative proportions in CN and decreasing the content and
      proportions of alpha(S1)-CN and alpha(S2)-CN and milk pH through selective
      breeding exert favorable effects on MCP.

PMID- 21943769
TI  - Production, reproduction, health, and growth traits in backcross Holstein *
      Jersey cows and their Holstein contemporaries.
AB  - A total of 648 purebred Holstein and 319 backcross Holstein * Jersey dairy cattle
      were compared for production, reproduction, health, linear type, and growth
      traits. Animals were born between 2003 and 2009 and were housed in the University
      of Wisconsin-Madison Integrated Dairy Facility. All animals had Holstein dams;
      lactating dams were mated to unproven Holstein sires to produce purebred
      (control) Holsteins or to unproven F(1) Jersey * Holstein crossbred sires to
      produce backcross animals, whereas nulliparous dams were mated to proven Holstein
      sires to produce purebred (other) Holsteins. Traits were analyzed using mixed
      linear models with effects of season of birth, age of dam, sire, birth year of
      sire, days in milk, lactation, and linear type score evaluator. Control Holsteins
      had greater 305-d milk yield (12,645 vs. 11,456 kg), 305-d mature equivalent milk
      yield (13,420 vs. 12,180 kg), peak daily milk yield (49.5 vs. 46.4 kg), total
      lactation milk yield (11,556 vs. 10,796 kg), and daily fat-corrected milk yield
      (43 vs. 40 kg) compared with backcrosses. Days open and services per conception
      as a heifer or cow did not differ between control Holsteins, other Holsteins, or
      backcrosses. The proportion of first-parity births that required assistance was
      less in control Holsteins than in backcross cows (3.7 vs. 11.2%). The incidence
      of scours or respiratory problems in calves did not differ between control
      Holsteins, other Holsteins, and backcrosses, nor did the incidence of mastitis,
      injury, or feet problems. Control Holstein heifers were heavier (629 vs. 557 kg),
      with greater hip height (145 vs. 139 cm), body length (167 vs. 163 cm), heart
      girth (205 vs. 198 cm), and hip width (54 vs. 53 cm) at 22 mo of age. On a 50
      point scale for linear type traits, Holsteins were larger in stature compared
      with backcrosses (41 vs. 28), had wider rumps (37 vs. 33), and wider rear udders
      (34 vs. 32). Results of this study suggest that backcross Holstein * Jersey
      cattle have decreased production but fail to demonstrate an advantage in health
      and reproduction compared with purebred Holsteins.

PMID- 21943770
TI  - Population structure and effects of inbreeding on milk yield and quality of
      Murrah buffaloes.
AB  - To provide data for conservation, selection, and expansion programs of buffalo
      herds, this study evaluated the history of a population of Murrah buffaloes based
      on population structure and the effect of inbreeding on accumulated 305-d milk
      yield (MY), fat yield (FY), protein yield (PY), mozzarella production (MProd),
      and somatic cell score (SCS). The usefulness of including the individual
      inbreeding coefficient (F) or individual increase in inbreeding coefficient
      (DeltaF) in the model to describe inbreeding depression was evaluated. Pedigree
      information from 8,054 animals born between 1976 and 2008 and 4,497 lactation
      records obtained from 12 herds were used. The realized effective population size
      was 40.10 +/- 1.27, and the mean F of the entire population was 2.14%. The ratio
      between the number of founders and ancestors demonstrated the existence of a
      bottleneck in the pedigree of this population, which may contribute to a
      reduction of genetic diversity. The effect of F on MY, FY, PY, MProd, and SCS was
      -1.005 kg, -0.299 kg, -0.246 kg, -1.201 kg, and -0.002 units, and the effect of
      DeltaF transformed to equivalent F (%) for a mean of 2.57 equivalent generations
      was -4.287 kg, -0.581 kg, -0.383 kg, -2.001 kg, and -0.007 units, respectively.
      The inbreeding depression observed may have important economic repercussions for
      production systems. The DeltaF can be considered the better of the two indicators
      of inbreeding depression due to its properties that prevent underestimation of
      this effect. A designed mating system to avoid inbreeding may be applied to this
      population to maintain genetic diversity.

PMID- 21943771
TI  - Short communication: A comparison between purebred Holstein and Brown Swiss *
      Holstein cows for milk production, somatic cell score, milking speed, and udder
      measurements in the first 3 lactations.
AB  - Brown Swiss * Holstein (BS * HO) crossbred cows (n = 55) and purebred Holstein
      (HO) cows (n = 50) were compared for milk yield, fat and protein production,
      somatic cell score, milking speed, and udder measurements for the first 3
      lactations. Cows from a designed experiment were housed in a freestall barn at
      the experimental station of the federal state of Saxony-Anhalt, Germany, and
      calved from July 2005 to August 2008. Best prediction was used to determine
      actual production for 305-d lactations from test-day observations. For the first
      3 lactations, BS * HO cows and HO cows were not significantly different for milk
      yield, fat and protein production, or SCS. Average milking time was significantly
      longer for BS * HO cows than for HO cows for first, second, and third lactations
      by 35, 51, and 30s, respectively. Average milking speed expressed as average
      yield per minute was significantly lower for BS * HO cows than for HO cows for
      the first 3 lactations by 0.19, 0.35, and 0.19 kg/min, respectively. Front and
      rear teats were significantly longer for BS * HO cows than for HO cows.
      Furthermore, front and rear udder clearance was significantly lower for BS * HO
      cows compared with HO cows in first and second lactations.

PMID- 21943772
TI  - Factors affecting consumers' preferences for and purchasing decisions regarding
      pasteurized and raw milk specialty cheeses.
AB  - Eight hundred ninety consumers at a local food festival were surveyed about their
      specialty cheese purchasing behavior and asked to taste and rate, through
      nonforced choice preference, 1 of 4 cheese pairs (Cheddar and Gouda) made from
      pasteurized and raw milks. The purpose of the survey was to examine consumers'
      responses to information on the safety of raw milk cheeses. The associated
      consumer test provided information about specialty cheese consumers' preferences
      and purchasing behavior. Half of the consumers tested were provided with cheese
      pairs that were identified as being made from unpasteurized and pasteurized milk.
      The other half evaluated samples that were identified only with random 3-digit
      codes. Overall, more consumers preferred the raw milk cheeses than the
      pasteurized milk cheeses. A larger portion of consumers indicated preferences for
      the raw milk cheese when the cheeses were labeled and thus they knew which
      samples were made from raw milk. Most of the consumers tested considered the raw
      milk cheeses to be less safe or did not know if raw milk cheeses were less safe.
      After being informed that the raw milk cheeses were produced by a process
      approved by the FDA (i.e., 60-d ripening), most consumers with concerns stated
      that they believed raw milk cheeses to be safe. When marketing cheese made from
      raw milk, producers should inform consumers that raw milk cheese is produced by
      an FDA-approved process.

PMID- 21943773
TI  - Changes in management practices and apparent prevalence on Canadian dairy farms
      participating in a voluntary risk assessment-based Johne's disease control
      program.
AB  - The objectives of this study were (1) to describe the change in Mycobacterium
      avium ssp. paratuberculosis (MAP) antibody milk ELISA-positive prevalence in
      Canadian dairy herds that participated in a risk assessment (RA)-based Johne's
      disease (JD) control program; (2) to describe the distribution of so-called high
      risk management practices on Canadian dairy farms; and (3) to assess if
      compliance with selected recommendations translated into changes in the scores of
      associated RA questions. In Ontario and western Canada, 226 herds voluntarily
      participated in a RA-based JD control program for several years. In 2005-2007, a
      previsit survey, RA, and MAP-antibody milk ELISA of the entire milking herd were
      conducted. Therefore, the interpretation of the results of this study is strictly
      for the MAP-antibody milk ELISA status of cows or herds, because no culture of
      MAP (of fecal or environmental samples) was conducted due to economic
      restrictions. In early 2008, a telephone interview was used to determine
      compliance with recommended management changes after the first RA. In 2008-2009,
      a second RA and another whole-herd MAP antibody milk ELISA were performed. At
      both herd tests, about 35% of the farms had at least one MAP-antibody milk ELISA
      positive cow, classifying them as a MAP-antibody milk ELISA-positive herd.
      However, 28.8% of herds had changed their MAP-antibody milk ELISA status between
      the 2 tests, demonstrating that a single herd test was insufficient to determine
      the long-term MAP-antibody ELISA status of a herd. The average within-herd MAP
      antibody milk ELISA-positive prevalence changed from 5.4 to 4.2% over the study
      period, but management practices did not change much throughout the 2- to 3-yr
      period and were similar to those reported in other parts of North America. The
      overall RA scores decreased at the second RA, in particular for management
      practices in the calving and preweaned calf area, and when herds were test
      positive at the first test. This was not surprising, because many of the
      recommendations at the first RA focused on these management areas and compliance
      with some recommended farm-specific management practices in this area might be
      linked to reduced scores for associated RA questions. In conclusion, the
      participating farms did, on average, decrease their within-herd MAP-antibody milk
      ELISA positive-prevalence and RA total scores. Changes in RA scores could be
      linked to improved management practices, indicating that the RA questions
      appropriately reflected management practices. Some herds changed their MAP
      antibody milk ELISA status between tests, which underlines that a current test of
      the entire milking herd is necessary to determine the present MAP-antibody milk
      ELISA status of a dairy herd.

PMID- 21943774
TI  - Survival characteristics of Salmonella enterica serovar Newport in the dairy farm
      environment.
AB  - Multi-drug resistant (MDR) Salmonella enterica serovar Newport (S. Newport) has
      established a reservoir in dairy cattle. Infected herds suffer significant
      mortality in both adult and young animals, posing a considerable economic loss to
      producers. Land application of manure from infected animals may further spread
      the pathogen into the agroecosystem, causing public health concerns. Previous
      work by our group demonstrated that the organism persisted in manure and manured
      soil for 6 to 10 mo under laboratory conditions. In the present study, we
      determined the survival characteristics of MDR S. Newport in a dairy lagoon,
      compost pile, and soil of a grass field under natural conditions using
      environmental sentinel chambers with an initial concentration of S. Newport
      around 7 log(10) per gram. In the static compost pile at 64  degrees C, S.
      Newport was eliminated within 18 h. In the dairy effluent lagoon, the pathogen
      survived for >137 d, whereas in the field soil, the organisms persisted for over
      276 d. The survival of MDR S. Newport in both the lagoon and field soil followed
      a pattern of (1) an increase or plateau for a few days, (2) log-linear decline
      for 6 to 13 wk, and (3) a long tailing phase at low and variable concentration
      for 4 to 9 mo. Log reduction times (days required for 90% decrease in
      concentration) based on the log-linear decline phase were 7 d in the lagoon and
      14 to 20 d in the soil. Conditions leading to faster inactivation during the
      initial phase do not necessarily translate into a quicker elimination of the
      pathogen. Regression models of the log-linear phase may be inaccurate for
      estimating complete pathogen elimination.

PMID- 21943775
TI  - Network modeling and analysis of lumbar muscle surface EMG signals during flexion
      extension in individuals with and without low back pain.
AB  - In this paper, we propose modeling the activity coordination network between
      lumbar muscles using surface electromyography (sEMG) signals and performing the
      network analysis to compare the lumbar muscle coordination patterns between
      patients with low back pain (LBP) and healthy control subjects. Ten healthy
      subjects and eleven LBP patients were asked to perform flexion-extension task,
      and the sEMG signals were recorded. Both the subject-level and the group-level
      PC(fdr) algorithms are applied to learn the sEMG coordination networks with the
      error-rate being controlled. The network features are further characterized in
      terms of network symmetry, global efficiency, clustering coefficient and graph
      modules. The results indicate that the networks representing the normal group are
      much closer to the order networks and clearly exhibit globally symmetric patterns
      between the left and right sEMG channels. While the coordination activities
      between sEMG channels for the patient group are more likely to cluster locally
      and the group network shows the loss of global symmetric patterns. As a
      complementary tool to the physical and anatomical analysis, the proposed network
      analysis approach allows the visualization of the muscle coordination activities
      and the extraction of more informative features from the sEMG data for low back
      pain studies.

PMID- 21943776
TI  - Can fluoroscopy radiation exposure be measured in minimally invasive trauma
      surgery?
AB  - Repeated use of X-rays in orthopedic surgery poses the problem of irradiation of
      patient and caregivers. Seven common minimally invasive bone trauma surgical
      procedures requiring image intensifier use were investigated: percutaneous K-wire
      fixation of the wrist, minimally invasive fixation plating of the wrist,
      percutaneous intramedullary nailing of the tibia and of the femur, short and long
      trochanteric nail fixation of trochanteric and sub-trochanteric fracture, and
      percutaneous fixation of thoracolumbar fracture. The study analyzed three
      parameters: dose area product (DAP), radiation duration, and skin entrance dose
      (SED). Data were collected from 15 successive implementations of each procedure.
      The aim of the study was to establish a database for this kind of bone trauma
      surgery and a hierarchy of the X-ray doses delivered. Percutaneous spinal
      osteosynthesis involved the highest dose, followed in decreasing order by long
      trochanteric nailing, femoral nailing, short trochanteric nailing, tibial
      nailing, wrist K-wire fixation and frontal wrist plate osteosynthesis. One short
      trochanteric nail procedure delivered the same DAP as 13 wrist K-wire fixation
      procedures, and one spinal osteosynthesis was equivalent to 13 short trochanteric
      nail or 174 wrist K-wire procedures. The anatomic area X-rayed appeared to be the
      main radiation dose factor. A database was established, but actual patient and
      staff radiation levels remained unknown.

PMID- 21943777
TI  - Re: Arnulf Stenzl, Nigel C. Cowan, Maria De Santis, et al. Treatment of muscle
      invasive and metastatic bladder cancer: update of the EAU Guidelines. Eur Urol
      2011;59:1009-18.

PMID- 21943778
TI  - Combining risk assessment and epidemiological risk factors to elucidate the
      sources of human E. coli O157 infection.
AB  - E. coli O157 can be transmitted to humans by three primary (foodborne,
      environmental, waterborne) and one secondary (person-to-person transmission)
      pathways. A regression model and quantitative microbiological risk assessments
      (QMRAs) were applied to determine the relative importance of the primary
      transmission pathways in NE Scotland. Both approaches indicated that waterborne
      infection was the least important but it was unclear whether food or the
      environment was the main source of infection. The QMRAs over-predicted the number
      of cases by a factor of 30 and this could be because all E. coli O157 strains may
      not be equally infective and/or the level of infectivity in the dose-response
      model was too high. The efficacy of potential risk mitigation strategies to
      reduce human exposure to E. coli O157 using QMRAs was simulated. Risk mitigation
      strategies focusing on food and environment are likely to have the biggest impact
      on infection figures.

PMID- 21943779
TI  - Role of cold shock Y-box protein-1 in inflammation, atherosclerosis and organ
      transplant rejection.
AB  - Chemokines (chemoattractant cytokines) are crucial regulators of immune cell
      extravasation from the bloodstream into inflamed tissue. Dysfunctional regulation
      and perpetuated chemokine gene expression are linked to progressive chronic
      inflammatory diseases and, in respect to transplanted organs, may trigger graft
      rejection. RANTES (regulated upon activation, normal T cell expressed and
      secreted (also known as CCL5)) is a model chemokine with relevance in numerous
      inflammatory diseases where the innate immune response predominates.
      Transcription factor Y-box binding protein-1 (YB-1) serves as a trans-regulator
      of CCL5 gene transcription in vascular smooth muscle cells and leucocytes. This
      review provides an update on YB-1 as a mediator of inflammatory processes and
      focuses on the role of YB-1 in CCL5 expression in diseases with monocytic cell
      infiltrates, albeit acute or chronic. Paradigms of such diseases encompass
      atherosclerosis and transplant rejection where cold shock protein YB-1 takes a
      dominant role in transcriptional regulation.

PMID- 21943780
TI  - Evaluation of set-up uncertainties with daily kilovoltage image guidance in
      external beam radiation therapy for gynaecological cancers.
AB  - AIMS: To assess the set-up uncertainty for gynaecological cancer patients treated
      with external beam radiation therapy using daily kilovoltage image guidance and
      to estimate set-up margins for treatment and factors that would predict higher
      set-up uncertainty. MATERIALS AND METHODS: Alignment data from daily two
      dimensional kilovoltage planar images and three-dimensional kilovoltage cone beam
      images for 52 patients treated on a Varian 2300iX linear accelerator with On
      Board Imaging (OBI; version 1.4) capability were analysed. The mean displacements
      of translational shifts, population systematic errors and random errors were
      calculated. Using van Herk's formula, the clinical target volume (CTV) to
      planning target volume (PTV) margins for set-up uncertainties were calculated.
      The differences in set-up error were calculated with respect to the type of
      cancer, imaging type and body mass index (BMI). RESULTS: Population systematic
      and random errors were 1.1 mm, 2.3 mm, 2.3 mm and 3.9 mm, 5.0 mm, 3.5 mm in the
      anterior-posterior (AP), medial-lateral (ML) and superior-inferior (SI)
      directions, respectively, for the entire patient population. Using van Herk's
      formula, the CTV to PTV margins for set-up uncertainties were found to be 5.5,
      9.1 and 8.3 mm in the AP, ML and SI directions respectively. The mean
      displacements in the AP, ML and SI directions for BMI >= 30 (28 patients) versus
      <30 (24 patients) were -0.1 mm, 0.9 mm and 1.0 mm versus -0.1 mm, 0.1 mm and 0.4
      mm, respectively, (P = 0.02). CONCLUSIONS: Daily imaging helps to assess set-up
      uncertainty. The set-up margin for CTV to PTV was larger for patients with BMI >=
      30 without image guidance and these patients would benefit more from daily image
      guidance.

PMID- 21943781
TI  - The association of the IVS1-397T>C estrogen receptor alpha polymorphism with the
      regulatory conditions in longstanding type 1 diabetic girls.
AB  - Type 1 diabetes is considered as pluricausal disease, whose etiology involves
      genetic predisposition as well as environmental factors that contribute to
      disease progression and pathogenesis. Women are believed to be more susceptible
      to develop autoimmune diseases, which may depend in part on the influence of sex
      hormones on the immune system. It was shown that estrogens may protect against
      the development of autoimmune disease by inducing the expansion of regulatory T
      cell pool and upregulating Foxp3 expression. Foxp3 is a transcription factor that
      controls the development and suppressive function of naturally occurring
      regulatory T cells CD4(+)Foxp3(+). Longstanding diabetes type 1 has features of
      low-grade chronic inflammation which may influence regulatory T cell subset by
      reducing their numbers or/and inhibiting their suppressive potential. As diabetic
      type 1 patients are differentiated with regard to metabolic factors, level of
      glycemic control and systemic inflammatory state, we aimed to examine if this can
      be associated with IVSI-397T>C estrogen receptor alpha polymorphism. We examined
      93 young regularly menstruating girls with diagnosed type 1 diabetes and 49
      healthy age-matched control individuals. The PvuII polymorphism of the ER-alpha
      gene was analyzed as well as the serum TNF level and the level of CD4(+)Foxp3(+)
      regulatory T cells in these individuals. Girls with type 1 diabetes had lower
      level of CD4(+)Foxp3(+) Tregs than their healthy counterparts. Regulatory T cells
      from these patients showed also lower expression of Foxp3 than Tregs in healthy,
      control group. In addition, DM1 girls bearing the CC genotypes showed the highest
      level of CD4(+)Foxp3(+) Tregs and the lowest TNF serum level in comparison to
      girls carrying CT or TT genotype. The CC DM1 carriers had also higher serum level
      of estrogens than girls bearing CT or TT genotype. We propose that different
      variants of IVS1-397 estrogen receptor alpha polymorphism may become additional
      genetic factor that influences regulatory conditions during diabetes type 1 in
      females.

PMID- 21943785
TI  - Controlling fibroblast proliferation with dimensionality-specific response by
      stiffness of injectable gelatin hydrogels.
AB  - We report an injectable hydrogel system with tunable stiffness for controlling
      the proliferation rate of human fibroblasts (HFF-1) in both two-dimensional (2D)
      and three-dimensional (3D) culture environments for potential use as a wound
      dressing material. The hydrogel composed of gelatin-hydroxyphenylpropionic acid
      (Gtn-HPA) conjugate was formed by the oxidative coupling of HPA moieties
      catalyzed by hydrogen peroxide (H2O2) and horseradish peroxidase (HRP). The
      stiffness of the hydrogels was controlled well by varying the H2O2 concentration.
      The effects of hydrogel stiffness on the proliferation rate of HFF-1 in both 2D
      and 3D were investigated. We found that the proliferation rate of HFF-1 using Gtn
      HPA hydrogels was strongly dependent on the hydrogel stiffness, with a
      dimensionality-specific response. In the 2D studies, the HFF-1 exhibited a higher
      proliferation rate when the stiffness of the hydrogel was increased. In contrast,
      the HFF-1 cultured inside the hydrogel remained non-proliferative for 12 days
      before a stiffness-dependent proliferation profile was shown. The proliferation
      rate decreased with an increase in stiffness of the hydrogel in a 3D culture
      environment, unlike in a 2D environment. 

PMID- 21943783
TI  - Immunoproteomic analysis of Brucella melitensis and identification of a new
      immunogenic candidate protein for the development of brucellosis subunit vaccine.
AB  - In order to screen immunogenic candidate antigens for the development of a
      brucellosis subunit vaccine, an immunoproteomic assay was used to identify
      immunogenic proteins from Brucella melitensis 16 M soluble proteins. In this
      study, a total of 56 immunodominant proteins were identified from the two
      dimensional electrophoresis immunoblot profiles by liquid chromatography tandem
      mass spectrometry (LC-MS/MS). Two proteins of interest, riboflavin synthase alpha
      chain (RS-alpha) and Loraine synthase (LS-2), which are both involved in
      riboflavin synthesis, were detected by two-dimensional immunoblots using antisera
      obtained from Brucella-infected human and goats. LS-2, however, is an already
      well-known vaccine candidate. Therefore, we focussed our studies on the novel
      vaccine candidate RS-alpha. B. melitensis RS-alpha and LS-2 were then expressed
      in Escherichia coli as fusion proteins with His tag. The humoral and cellular
      immune responses to the recombinant (r)RS-alpha was characterized. In response to
      in vitro stimulation by rRS-alpha, splenocytes from mice vaccinated with rRS
      alpha were able to produce gamma-interferon (IFN-gamma) and interleukin (IL)-2
      but not interleukin (IL)-4 and interleukin (IL)-10. Furthermore, rRS-alpha or rLS
      2-vaccinated mice were partially protected against B. melitensis infection. Our
      results suggested that we have developed a high-throughout, accurate, rapid and
      highly efficient method for the identification of candidate antigens by a
      combination of immunoproteomics with immunisation and bacterial challenge and rRs
      alpha could be a useful candidate for the development of subunit vaccines against
      B. melitensis.

PMID- 21943782
TI  - Regulatory immune responses induced by IL-1 receptor antagonist in rheumatoid
      arthritis.
AB  - Anakinra, a human recombinant IL-1 receptor antagonist, is approved for the
      treatment of RA. In this study, 12 patients received the placebo plus MTX
      treatment, 38 patients received Anakinra combined with MTX treatment. Compared
      with the placebo plus MTX group, serum levels of IL-17, IFN-gamma, IL-21 and IL
      1beta significantly decreased, the percentages of Th17 cells and Th1 cells were
      lower and the percentage of Treg cells was higher after receiving Anakinra
      combined with MTX treatment. The observed regulatory immune responses
      collectively correlated with clinical improvement in treated patients. A
      substantial response, ACR 20 at 24 w were consistent with those at 12 w, 16 w and
      20 w, and was accompanied by a marked improvement in RA related laboratory
      parameters. The study reveals that the combination of Anakinra and MTX is safe
      and well tolerated, which induces regulatory immune responses and significantly
      provides greater clinical benefit than the placebo plus MTX group.

PMID- 21943784
TI  - Protein kinase-regulated expression and immune function of thioredoxin reductase
      1 in mouse macrophages.
AB  - Macrophages exposed to lipopolysaccharide (LPS) exhibit radical changes in mRNA
      and protein profiles. This shift in gene expression is geared not only to
      activate immune effector and regulatory mechanisms, but also to adjust the immune
      cell's metabolism to new physiological demands. However, it remains largely
      unknown whether immune function and metabolic state are mutually regulatory and,
      if so, how they are mechanistically interrelated in macrophages. Selenium, a
      dietary trace element exerting pleiotropic effects on immune homeostasis, and
      selenium-containing proteins (selenoproteins) may play a role in such
      coordination. We examined the incorporation of radiolabeled selenium into protein
      during LPS stimulation, and identified thioredoxin reductase 1 (TR1) as the only
      LPS-inducible selenoprotein in macrophages. TR1 induction occurred at the
      transcriptional level and depended on the intracellular signaling pathways
      mediated by p38 MAP kinase and IkappaB kinase. Macrophage-specific ablation of
      TR1 in mice resulted in a drastic decrease in the expression of VSIG4, a B7
      family protein known to suppress T cell activation. These results reveal TR1 as
      both a regulator and a regulated target in the macrophage gene expression
      network, and suggest a link between selenium metabolism and immune signaling.

PMID- 21943787
TI  - Diagnosis and management of Brugada Syndrome.
AB  - Brugada Syndrome (BS) is a cardiac ion channel disorder linked to loss of
      function mutation in the SCN5A gene which affects the sodium current. The
      diagnosis is made on the ECG showing characteristic cove-shaped ST elevation in
      leads V(1) to V(3) in the absence of structural heart disease, electrolyte
      disturbance or ischaemia. This condition is genetically transmitted as an
      autosomal dominant syndrome with incomplete penetrance. It is responsible for 20%
      of all sudden deaths in those without structural heart disease. Diagnosis of BS
      can be difficult as the ECG changes are dynamic and variable. Genetic mutation in
      SCN5A gene is found in 25-30% of patients with Brugada Syndrome. Patients may
      present with syncope due to polymorphic VT or resuscitated sudden death in the
      third or fourth decade of life. Symptoms frequently occur at night or at rest and
      fever is a common trigger in children. Patients presenting with syncope or
      resuscitated sudden cardiac death should have an implantable defibrillator.
      Management of asymptomatic patients is controversial and risk stratification is
      required. www.brugadadrugs.org gives a list of drugs that should be avoided by
      patients suffering from BS.

PMID- 21943789
TI  - Biomechanical behaviors of curved artery with flexible wall: a numerical study
      using fluid-structure interaction method.
AB  - Studies showed that vascular diseases were prone to occur in curved arteries. In
      this paper, biomechanical behaviors of curved artery with flexible wall subjected
      to physiological flow were presented. Fluid-structure interaction effect was
      considered. The Von Mises stress variation and distribution patterns, the
      influence of artery curvature and flexibility on peak wall Von Mises stress,
      diameter change and cross sectional shape variation of the curved artery in the
      cardiac cycle were studied in detail. We believe that the findings may provide
      important implications for individualized treatment for patients with
      cardiovascular disease.

PMID- 21943788
TI  - Tumor necrosis factor receptor associated periodic fever syndrome with
      photographic evidence of various skin disease and unusual phenotypes: case report
      and literature review.
AB  - OBJECTIVES: To report a case of tumor necrosis factor receptor associated
      periodic fever syndrome (TRAPS) with unusual clinical phenotypes and a systematic
      review. METHODS: The relevant English literature of TRAPS was searched using the
      keywords TRAPS, autoinflammatory disease, and gene mutation. Original and review
      articles were reviewed and the clinical scenarios were exemplified with a case
      report. RESULTS: A 58-year-old Jewish woman with Eastern European Ashkenazic
      background presented with photographic evidence of various skin disease,
      including previously unreported vesicles and alopecia, as well as other systemic
      manifestations. The complaints of urinary foreign bodies prompted a discovery of
      ureteral strictures with atypia perhaps from autoinflammation. A R92Q gene
      mutation of TNFRSFA1 was detected. The clinical manifestations of this disease
      are protean and its pathogenesis is complex, involving the interaction of wild
      type and mutated gene products, innate immune system, and proinflammatory
      cytokines. Glucocorticoid and anticytokine therapy is generally efficacious but
      some cases remain refractory to the current treatment. CONCLUSIONS: TRAPS is a
      systemic autoinflammatory disease with variable clinical phenotypes associated
      with gene mutations. Recognition of the unusual phenotypes may enhance early
      accurate diagnosis.

PMID- 21943786
TI  - Reproducibility of choroidal thickness measurements across three spectral domain
      optical coherence tomography systems.
AB  - PURPOSE: To investigate the reproducibility of choroidal thickness measurements
      in normal subjects on 3 spectral domain optical coherence tomography (SD-OCT)
      instruments: Zeiss Cirrus HD-OCT (Carl Zeiss Meditec Inc., Dublin, CA),
      Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany), and Optovue
      RTVue (Optovue Inc., Fremont, CA). DESIGN: Cross-sectional non-interventional
      study. PARTICIPANTS: Images were obtained in 28 eyes of 28 healthy undilated
      volunteers without ocular pathology in a clinical setting. METHODS: All subjects
      were imaged on the fovea using Cirrus HD 1-line raster, Spectralis enhanced depth
      imaging (EDI), and RTVue retina-cross. MAIN OUTCOME MEASURES: The choroid was
      measured subfoveally, 750 MUm temporal, and 750 MUm nasal to the fovea. All
      measurements were performed by 2 independent observers. Two-way analysis of
      variance (ANOVA) with Bonferroni's post-test, Pearson correlation, and Bland
      Altman analysis were used to compare measurements. RESULTS: The group of 28
      subjects consisted of 7 men and 21 women, with an average age of 35.2 years
      (range, 23-64 years). A 2-way ANOVA with Bonferroni's post-test revealed no
      significant difference in the average subfoveal choroidal thickness (P > 0.05)
      among systems for any location: subfoveally, 750 MUm temporal, and 750 MUm nasal
      to the fovea. The measurements of choroidal thickness from any pair of 3
      instruments (Cirrus vs. Spectralis, Cirrus vs. RTVue, Spectralis vs. RTVue) were
      also strongly correlated. The Pearson correlation among all 2 system pairs of the
      3 systems was greater than 0.9 (P < 0.0001). The 95% limits of agreement among 4
      choroidal thickness measurements were +11.21% to -13.57% (bias -1.17) between
      Cirrus and RTVue, +10.85% to -12.45% (bias -0.80) between Spectralis and RTVue,
      and +12.81% to -13.33% (bias -0.25) between Cirrus and Spectralis. CONCLUSIONS:
      In our population of young healthy adults with normal vision, there was good
      reproducibility among choroidal thickness measurements of images acquired with
      Cirrus, Spectralis, and RTVue. FINANCIAL DISCLOSURE(S): Proprietary or commercial
      disclosure may be found after the references.

PMID- 21943790
TI  - The reporting of previous lifestyle counseling by persons at high risk of Type 2
      diabetes.
AB  - OBJECTIVE: To assess (i) whether the reporting of counseling previously received
      is associated with high-risk individuals' agreement to participate in lifestyle
      intervention, (ii) whether the reporting of previous counseling differed within
      such a high-risk group, and (iii) the associations between lifestyles and
      previous lifestyle counseling. METHODS: Cross-sectional data were drawn from
      10149 adults at high risk of Type 2 diabetes, who were participating in a Finnish
      national diabetes prevention project (FIN-D2D). Bivariate analysis and
      multivariate logistic regression were used. RESULTS: In relation to the reporting
      of previous counseling, no difference was found between persons who had agreed
      and persons who had not agreed to participate in the lifestyle intervention.
      Persons who were more educated or who had dyslipidemia or diabetes were more
      likely than the others to report previous counseling. A generally healthy
      lifestyle, or certain health behaviors (being a non-smoker or eating large
      amounts of fruit and vegetables) may make the reporting of previous counseling
      more likely. CONCLUSION: The results raise questions about the amount and quality
      of the previously received lifestyle counseling. PRACTICE IMPLICATIONS: There is
      a need for sustainable lifestyle counseling structures, within vigorously
      implemented diabetes prevention projects, if long-lasting lifestyle changes are
      to be achieved.

PMID- 21943791
TI  - "Jum'ah" syndrome.
AB  - This is my memoir as a sick child, hospitalized in the Pediatric ward of a large
      hospital, many years ago. The story tells about my friendship with another young
      patient, Jum'ah, a Bedouin child who suffered from Congenital Cyanotic Heart
      Disease, to whom the pediatric ward was Home. My Childish understanding of
      Jum'ah's loneliness, anxiety and struggle to be loved and belonged are described
      in this narrative. I describe how this experience still has an influence on my
      adult professional and personal concepts.

PMID- 21943793
TI  - Effects of Poisson's ratio on the band gaps and defect states in two-dimensional
      vacuum/solid porous phononic crystals.
AB  - The effects of the Poisson's ratio of the solid host on the band gaps and point
      defect states of the mixed elastic wave modes in two-dimensional vacuum/solid
      porous PNCs are studied by numerical simulations. Four typical systems are
      considered. The four systems are, respectively, (I) the system with a square
      lattice and circular pores, (II) the system with a hexagonal lattice and circular
      pores, (III) the system with a square lattice and square pores and (IV) the
      system with a hexagonal lattice and regular-hexagonal pores. In the latter two
      systems, with respect to the outer boundaries of the Wigner-Seitz unit cell, the
      pores rotate 45 degrees  and 30 degrees , respectively. Some observable effects
      of the Poisson's ratio are found in the numerical results. Especially, the
      variations of the band gap boundaries with the Poisson's ratio exhibit relatively
      consistent behaviors. With the increase of the Poisson's ratio, the normalized
      frequency of a band gap boundary generally increases, except that in system (III)
      the normalized frequency of the upper boundary of the first band gap remains
      almost unchanged. Detailed interpretations on this phenomenon are given.

PMID- 21943792
TI  - Milrinone and mortality in adult cardiac surgery: a meta-analysis.
AB  - OBJECTIVE: The authors conducted a review of randomized studies to show whether
      there are any increases or decreases in survival when using milrinone in patients
      undergoing cardiac surgery. DESIGN: A meta-analysis. SETTING: Hospitals.
      PARTICIPANTS: Five hundred eighteen patients from 13 randomized trials.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: BioMedCentral, PubMed EMBASE,
      the Cochrane central register of clinical trials, and conference proceedings were
      searched for randomized trials that compared milrinone versus placebo or any
      other control in the setting of cardiac surgery that reported data on mortality.
      Overall analysis showed that milrinone increased perioperative mortality (13/249
      [5.2%] in the milrinone group v 6/269 [2.2%] in the control arm, odds ratio [OR]
      = 2.67 [1.05-6.79], p for effect = 0.04, p for heterogeneity = 0.23, I(2) = 25%
      with 518 patients and 13 studies included). Subanalyses confirmed increased
      mortality with milrinone (9/84 deaths [10.7%] v 3/105 deaths [2.9%] with other
      drugs as control, OR = 4.19 [1.27-13.84], p = 0.02) with 189 patients and 5
      studies included) but did not confirm a difference in mortality (4/165 [2.4%] in
      the milrinone group v 3/164 [1.8%] with placebo or nothing as control, OR = 1.27
      [0.28-5.84], p = 0.76 with 329 patients and 8 studies included). CONCLUSIONS:
      This analysis suggests that milrinone might increase mortality in adult patients
      undergoing cardiac surgery. The effect was seen only in patients having an active
      inotropic drug for comparison and not in the placebo subgroup. Therefore, the
      question remains whether milrinone increased mortality or if the control
      inotropic drugs were more protective.

PMID- 21943795
TI  - [Management of extruded haptic of an anterior chamber lens].

PMID- 21943794
TI  - Hormonal therapies and meningioma: is there a link?
AB  - BACKGROUND: The aetiology of meningiomas is largely unknown although hormones
      have been suggested to play a role. METHODS: A cohort study was performed to
      evaluate hormone-related factors associated with meningioma. Patients (12-89
      years) with a first diagnosis of meningioma (January 1996-June 2008) were
      identified from The Health Improvement Network UK primary care database and age-
      and sex-matched to controls (n=10000) from the same cohort. Odds ratios (ORs)
      were calculated following a nested case control analysis using unconditional
      logistic regression. RESULTS: In total, 745 patients with meningioma were
      identified from a study population of 2171287. No significantly increased risk of
      meningioma was found among female users of oral contraceptives (OR: 1.15; CI:
      0.67-1.98), hormone replacement therapy (OR: 0.99; CI: 0.73-1.35) or low-dose
      cyproterone acetate (CPA; OR: 1.51; CI: 0.33-6.86) compared with non-users. There
      was a significantly increased risk of meningioma among male users of androgen
      analogues (OR: 19.09; CI: 2.81-129.74) and among users of high-dose CPA (OR:
      6.30; CI: 1.37-28.94) compared with non-users, however there were only three
      cases currently using these drugs. No significant association was found between
      meningioma and prostate, breast, or genital cancers. CONCLUSIONS: Our results do
      not support a role for exogenous hormone use by females in meningioma
      development. The risk in males was only observed with high-dose, short-term (<1
      year) therapy. IMPACT: While hormonal cancers and therapies are not associated
      with meningioma in females, the risk in males requires further investigation.

PMID- 21943796
TI  - [Management of neovascular glaucoma related to the persistence after retinal
      detachment surgery of a circumferential peripheral retinal detachment].
AB  - OBSERVATION: A 41-year-old male with a medical history of high myopia and several
      retinal detachment (RD) surgeries was referred for vitreous hemorrhage coexisting
      with neovascular glaucoma occurring 2 months after uncomplicated silicone oil
      removal on his left and single eye. The right eye had been lost to RD. The retina
      behind the equator was reattached on ultrasonography. We performed a washout pars
      plana vitrectomy on the left eye, revealing a chronic circumferential RD of the
      anterior retina stopped in its posterior spread by dense photocoagulation scars.
      We combined a retinectomy of the detached retina with an intracamerular injection
      of bevacizumab, resulting in complete disappearance of rubeosis and normalization
      of the intraocular pressure. CONCLUSIONS: The retinal ischemia related to the
      persistence of a chronic and circumferential RD anterior to dense
      photocoagulation scars after ab-interno RD surgery, whereas the rest of the
      retina appears reattached, is probably the causative factor of neovascular
      glaucoma. In the present case, the removal of RD by circumferential retinectomy
      combined with an intraocular injection of anti-VEGF allowed the complete and
      definitive regression of neovascular glaucoma.

PMID- 21943798
TI  - A cholera outbreak among semi-nomadic pastoralists in northeastern Uganda:
      epidemiology and interventions.
AB  - In sub-Saharan Africa, many nomadic pastoralists have begun to settle in
      permanent communities as a result of long-term water, food, and civil insecurity.
      Little is known about the epidemiology of cholera in these emerging semi-nomadic
      populations. We report the results of a case-control study conducted during a
      cholera outbreak among semi-nomadic pastoralists in the Karamoja sub-region of
      northeastern Uganda in 2010. Data from 99 cases and 99 controls were analysed. In
      multivariate analyses, risk factors identified were: residing in the same
      household as another cholera case [adjusted odds ratio (aOR) 6.67, 95% confidence
      interval (CI) 2.83-15.70], eating roadside food (aOR 2.91, 95% CI 1.24-6.81), not
      disposing of children's faeces in a latrine (aOR 15.76, 95% CI 1.54-161.25), not
      treating drinking water with chlorine (aOR 3.86, 95% CI 1.63-9.14), female gender
      (aOR 2.43, 95% CI 1.09-5.43), and childhood age (10-17 years) (aOR 7.14, 95% CI
      1.97-25.83). This is the first epidemiological study of cholera reported from a
      setting of semi-nomadic pastoralism in sub-Saharan Africa. Public health
      interventions among semi-nomadic pastoralists should include a two-faceted
      approach to cholera prevention: intensive health education programmes to address
      behaviours inherited from insecure nomadic lifestyles, as well as improvements in
      water and sanitation infrastructure. The utilization of community-based village
      health teams provides an important method of implementing such activities.

PMID- 21943797
TI  - [Perfluorocarbon liquids and vitreoretinal surgery in 2011].
AB  - Perfluorocarbon liquids (PFCLs) are one of the most innovative recent tools for
      vitreoretinal surgery. PFCLs are characterized by their number of carbon atoms,
      which has an impact on the density, viscosity, surface tension, vapor pressure,
      the boiling point, and the refraction index. PFCLs are routinely used because of
      their high gravity (double that of water) and their low viscosity. Furthermore,
      they are immiscible in water, optically clear with refraction indices similar to
      that of water, allowing visualization of an interface between the PFCL and
      saline. The use of intravitreally injected liquid PFCLs as adjunctive agents to
      vitreoretinal surgery plays an important role in facilitating retinal
      reattachment, especially in cases of giant retinal tear, trauma, and/or
      proliferative vitreoretinopathy. PFCLs are also used as intraoperative
      instruments to re-establish intraocular volume, assist in separating membranes
      adherent to the retina (in proliferative diabetic retinopathy, for example), and
      manage the dislocated crystalline lens and intraocular lens.

PMID- 21943799
TI  - Proprotein convertase subtilisin/kexin type 9 (PCSK9): from structure-function
      relation to therapeutic inhibition.
AB  - AIMS: This short review aims at summarizing the current information on Proprotein
      Convertase Subtilisin/Kexin type 9 (PCSK9) structure and function focusing also
      on the therapeutic possibilities based on the inhibition of this protein. DATA
      SYNTHESIS: PCSK9 has been recently discovered as the third gene involved in
      autosomal dominant hypercholesterolemia. PCSK9 binds and favors degradation of
      the low-density lipoprotein receptor (LDLR) and thereby modulates the plasma
      levels of LDL-cholesterol (LDL-C). Some of the natural occurring PCSK9 mutations
      increase the protein function (gain of function) and cause hypercholesterolemia,
      whereas loss of function mutations associate with hypocholesterolemia. Since the
      loss of a functional PCSK9 in humans is not associated with apparent deleterious
      effects, this protease is an attractive target for the development of lowering
      plasma LDL-C agents, either alone or in combination with statins. CONCLUSION:
      Inhibition of PCSK9 is emerging as a novel strategy for the treatment of
      hypercholesterolemia and data obtained from pre-clinical studies show that use of
      monoclonal antibodies, antisense oligonucleotides and short interfering RNA are
      effective in reducing LDL-C, clinical studies, accompanied by a better
      understanding of PCSK9 biology, are now necessary to address whether these new
      compounds will have a future in clinical practice.

PMID- 21943800
TI  - A dynamically cultured collagen/cells-incorporated elastic scaffold for small
      diameter vascular grafts.
AB  - There is an essential demand for tissue-engineered autologous small-diameter
      vascular grafts, which offer temporary supports and guides for vascular tissue
      organization, repair and remodeling. This study reports on the effect of
      collagen/smooth muscle cells (SMCs) mixtures under dynamic cultures and SMC
      endothelial cell (ECs) co-culture on cell proliferation, uniform cell
      distribution, extracellular matrix deposition, and endothelial cells monolayer
      formation in tissue-engineered tubular arterial constructs of 4 mm inner
      diameter. Rabbit aortic SMCs were infiltrated with collagen solution in poly(L
      lactide-co-epsilon-caprolactone) (PLCL) scaffolds under vacuum to form
      collagenous gel and subjected to dynamic strain by culturing them in a dynamic
      perfusion bioreactor. The construct lumen was subsequently seeded with ECs and
      experiments were completed to create ECs-SMCs co-culture constructs. The
      collagen/SMCs incorporated elastic scaffold cultured under dynamic culture
      conditions promoted matrix deposition, leading to the development of tissue
      engineered vascular constructs, and induced SMC to have more uniform cell
      distribution. Scanning electron microscopic examination and von Willebrand Factor
      staining demonstrated the presence of ECs spread over the lumen. Quantitative
      analysis of elastin contents demonstrated that the engineered vessels acquired
      similar elastin contents as native arteries. The collagen/SMCs/ECs incorporated
      PLCL scaffolds under dynamic culture conditions can be used as a scaffold for
      tissue engineering to facilitate small-diameter vascular-tissue formation. 

PMID- 21943803
TI  - Medical missions, surgical education, and capacity building.

PMID- 21943801
TI  - Do regulatory antibodies offer an alternative mechanism to explain the hygiene
      hypothesis?
AB  - The 'hygiene hypothesis', or lack of microbial and parasite exposure during early
      life, is postulated as an explanation for the recent increase in autoimmune and
      allergic diseases in developed countries. The favored mechanism is that microbial
      and parasite-derived products interact directly with pathogen recognition
      receptors to subvert proinflammatory signaling via T regulatory cells, thereby
      inducing anti-inflammatory effects and control of autoimmune disease. Parasites,
      such as helminths, are considered to have a major role in the induction of immune
      regulatory mechanisms among children living in developing countries. Invoking
      Occam's razor, we believe we can select an alternative mechanism to explain the
      hygiene hypothesis, based on antibody-mediated inhibition of immune responses
      that may more simply explain the available evidence.

PMID- 21943802
TI  - A framework for the evaluation of "value" and cost-effectiveness in the
      management of critical limb ischemia.

PMID- 21943805
TI  - Gaps in the supply of physicians, advanced practice nurses, and physicians
      assistants.

PMID- 21943808
TI  - A multidimensional approach to impulsivity changes in mild Alzheimer's disease
      and control participants: cognitive correlates.
AB  - INTRODUCTION: Impulsive behaviors are frequently described in brain-damaged
      patients, including patients with Alzheimer's disease (AD). However, few studies
      have examined impulsivity changes and associated cognitive impairments in AD and
      healthy controls. Consequently, the first aim of this study was to compare
      patients with mild AD and matched controls on four dimensions of impulsivity
      (urgency, lack of premeditation, lack of perseverance, and sensation seeking)
      recently highlighted in the literature. The second objective was to examine the
      association between impulsivity changes and cognitive performances on
      executive/attentional tasks in mild AD and healthy controls. METHODS: Thirty
      patients with mild AD and 30 matched controls were administered a battery of
      tests that assessed executive and attention processes. In addition, informants of
      each patient and control completed a short questionnaire designed to assess the
      changes on the four dimensions of impulsivity (Rochat et al., 2008). RESULTS:
      Patients with mild AD had higher scores than controls on lack of premeditation
      and lack of perseverance dimensions of impulsivity, whereas the two groups did
      not differ on urgency and sensation seeking. Furthermore, patients showed
      significant decreased performances on measures of inhibition of prepotent
      responses, set-shifting, and working memory, as well as higher variability of
      reaction times (RTs) than matched controls. Regression analyses computed on the
      whole sample emphasized that difficulties in inhibition of prepotent responses
      significantly predicted higher lack of premeditation, and larger variability of
      RTs and set-shifting difficulties significantly predicted higher lack of
      perseverance, even when global cognitive functioning, general processing speed,
      working memory, and age were controlled for. Urgency and sensation seeking were
      not associated with any variables. CONCLUSIONS: These results provide valuable
      insight into the nature of brain systems and cognitive processes underlying
      impulsive behaviors. In addition, they open up interesting prospects for better
      comprehension of behavioral and psychological symptoms of AD.

PMID- 21943809
TI  - How do components of evidence-based psychological treatment cluster in practice?
      A survey and cluster analysis.
AB  - Evidence-based psychological treatments (EBPTs) are clusters of interventions,
      but it is unclear how providers actually implement these clusters in practice. A
      disaggregated measure of EBPTs was developed to characterize clinicians'
      component-level evidence-based practices and to examine relationships among these
      practices. Survey items captured components of evidence-based treatments based on
      treatment integrity measures. The Web-based survey was conducted with 75 U.S.
      Department of Veterans Affairs (VA) substance use disorder (SUD) practitioners
      and 149 non-VA community-based SUD practitioners. Clinician's self-designated
      treatment orientations were positively related to their endorsement of those EBPT
      components; however, clinicians used components from a variety of EBPTs.
      Hierarchical cluster analysis indicated that clinicians combined and organized
      interventions from cognitive-behavioral therapy, the community reinforcement
      approach, motivational interviewing, structured family and couples therapy, 12
      step facilitation, and contingency management into clusters including empathy and
      support, treatment engagement and activation, abstinence initiation, and recovery
      maintenance. Understanding how clinicians use EBPT components may lead to
      improved evidence-based practice dissemination and implementation.

PMID- 21943810
TI  - Randomized trial of a reentry modified therapeutic community for offenders with
      co-occurring disorders: crime outcomes.
AB  - This article describes a randomized study to determine the effectiveness of a
      reentry modified therapeutic community (RMTC) for offenders with co-occurring
      substance use and mental disorders (co-occurring disorders or COD). Men with COD,
      approved for community corrections placement postrelease, were recruited from
      nine Colorado prisons and stratified according to the type of treatment received
      while incarcerated (i.e., a prison modified therapeutic community [MTC] program
      or standard care). When released, each offender was randomly assigned either to
      the experimental RMTC (E-RMTC) condition (n = 71) or to the control parole
      supervision and case management (PSCM) condition (n = 56). An intent-to-treat
      analysis 12 months postprison release showed that the E-RMTC participants were
      significantly less likely to be reincarcerated (19% vs. 38%), with the greatest
      reduction in recidivism found for participants who received MTC treatment in both
      settings. These findings support the RMTC as a stand-alone intervention and
      provide initial evidence for integrated MTC programs in prison and in aftercare
      for offenders with COD.

PMID- 21943813
TI  - Clinical usefulness of a high-concentration calcium chloride solution method to
      correct the activated partial thromboplastin time in a high hematocrit model with
      heparin therapy.

PMID- 21943815
TI  - Safety and dose flexibility clinical evaluation of intravesical liposome in
      patients with interstitial cystitis or painful bladder syndrome.
AB  - To present single institution open-label experience with intravesical liposomes
      (LPs), a mucosal protective agent, in patients with interstitial cystitis/painful
      bladder syndrome (IC/PBS) and to assess the safety and efficacy on IC/PBS
      symptoms. A total of 17 symptomatic IC/PBS patients were treated with
      intravesical LPs (80mg/40mL distilled water) once a week for 4 weeks (n=12) or
      twice a week treatment for 4 weeks (n=5). The primary outcome was the change in
      the O'Leary-Sant Symptom/Problem score and O'Leary-Sant total Score from baseline
      to Week 4 and Week 8. Other outcome measurements included the changes in pain
      scale, urgency scale, voiding log, and patient global assessment. Both weekly and
      biweekly LP instillation regiments were well tolerated. The incidence of urinary
      incontinence, retention, or unanticipated adverse changes was not noted at any
      dose either during the treatment or at the 4-week follow-up. The O'Leary-Sant
      Symptom/Problem score, O'Leary-Sant total Score, and pain score were
      significantly improved from baseline at both dose regimens with added benefit
      with the biweekly regimen. Intravesical LPs treatment is safe and its efficacy
      has sustained duration. Furthermore large-scale, placebo-controlled studies are
      warranted to assess the efficacy for this promising new treatment for IC/PBS.

PMID- 21943812
TI  - Predictive factors for treatment retention in methadone programs in Indonesia.
AB  - This article presents the results of a 6-month prospective cohort study of
      methadone maintenance treatment (MMT) in Indonesia. The study aimed to
      investigate the predictor variables of retention in MMT in Indonesia. The
      duration of treatment (in days) was the main outcome of the study. For the study,
      program, client, social network, and accessibility factors were investigated as
      potential predictors of retention. The study analyzed the relative weight of each
      factor in predicting treatment retention. The sample consisted of 178 clients
      drawn from three participating clinics: Rumah Sakit Ketergantungan Obat and
      Tanjung Priok in Jakarta and Sanglah in Bali. The 3- and 6-month retention rates
      were 74.2% and 61.3%, respectively. These rates are comparable with previous
      studies conducted in developed countries. A survival analysis using a robust
      estimation for the Cox PH regression found that the strongest predictors of
      retention were methadone dose followed by an interaction between take-home dose
      and the experience of the clinic providing this treatment. Other significant
      predictor variables included age, perceived clinic accessibility, and client's
      belief in the program. The study concludes that MMT cannot solely rely on the
      pharmacology for retention but should also promote informed access to take-home
      doses.

PMID- 21943814
TI  - Risk factors for the leakage of chemotherapeutic agents into systemic circulation
      after transcatheter arterial chemoembolization of hepatocellular carcinoma.
AB  - This prospective study was to investigate the possible risk factors for the
      leakage of chemotherapeutic agent into the systemic circulation after
      transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma
      (HCC). Peripheral plasma concentrations of chemotherapeutic agents were
      determined at 1 hour and 72 hours after TACE by high-performance liquid
      chromatography in 53 patients. HCC were divided into three types namely single
      nodule (<5cm), multiple nodules (all <5cm), and main nodule measuring 5cm or
      more. Forty-four patients (83%) showed detectable chemotherapeutic concentrations
      within 72 hours after TACE. Patients with single nodular-type HCC had lower
      incidence of detectable plasma chemotherapeutic agents after TACE than the other
      two groups (all p<0.05). The injected doses of lipiodol, epirubicin, and
      mitomycin C were lower in patients without detection than in patients with
      detectable chemotherapeutic agents (all p<0.05). Multivariate logistic regression
      showed that tumor type and injected dose of lipiodol were two independent risk
      factors for the leakage of mitomycin C at 1 hour after TACE (all p<0.05), and the
      injected dose of mitomycin C was the risk factor for the leakage of epirubicin at
      1 hour after TACE (p<0.05). In conclusion, multiple nodular type and large nodule
      measuring 5cm or more have a risk of leakage of mitomycin C after TACE. Injected
      dose of lipiodol and mitomycin C as risk factor for the leakage of mitomycin C
      and epirubicin respectively may be because of competition of their injected
      volume within the limited space of target.

PMID- 21943816
TI  - Association between HLA-DQA1, HLA-DQB1 and oral cancer.
AB  - Cancer is one of the most common causes of morbidity and mortality. Genes whose
      products play a critical role in regulation of the immune response include the
      HLA antigen and cytokine families of genes. Oral cancer is common in men in
      developing countries, and its frequency is increased by using betel-quid,
      tobacco, and alcohol. The association between certain HLA Class I and Class II
      haplotypes and cancer has been documented in a variety of tumors. There was no
      previous data concerning the association of specific HLA Class II DQA1, DQB1
      alleles, or haplotypes with oral cancer patients. In this study, we enrolled 134
      Taiwanese patients with histologically confirmed oral cancer and 268 age- and
      gender-matched healthy Taiwanese adults as control group to investigate the
      association between HLA-DQA1, HLA-DQB1 allele frequencies and oral cancer
      patients by using polymerase chain reaction with sequence-specific primers. We
      found that both HLA-DQA1* and HLA-DQB1* allele frequencies in oral cancer
      patients revealed no significant difference from those of control groups.
      Haplotype frequencies of HLA*DQA1-0103-DQB1*0601 in oral cancer patients were
      significantly lower than those of the control group (odds ratio: 0.18, 95%
      confidence interval: 0.054-0.583, p(c)=0.02). Our data suggest that HLA DQA1*0103
      DQB1*0601 haplotype may be protective with regard to the development of oral
      cancer.

PMID- 21943811
TI  - Psychological, peer, and family influences on smoking among an adolescent
      psychiatric sample.
AB  - Although much is known about adolescent cigarette use and initiation in community
      samples, less is known about these factors among adolescents in clinic-referred
      populations or those with severe psychopathology. Data were collected from 106
      adolescents aged 12 to 15 years (M = 13.6, SD = 0.74) recruited from a
      psychiatric inpatient facility. Hierarchical logistic regressions assessed the
      relationship among psychological, peer, and family environment factors and
      smoking at baseline and 18 months posthospitalization. Conduct problem symptoms,
      friends' cigarette use, and friends' marijuana use were associated with greater
      odds of lifetime and current smoking at baseline but not at follow-up. After
      accounting for the significant effect of baseline use, greater family conflict
      predicted decreased odds of having initiated smoking at the 18-month follow-up.
      The period following inpatient psychiatric hospitalization may represent an
      important window for smoking cessation and prevention efforts targeting peer and
      family factors, especially for youth with externalizing problems.

PMID- 21943817
TI  - Motor ability and adaptive function in children with attention deficit
      hyperactivity disorder.
AB  - Attention deficit hyperactivity disorder (ADHD) is a common neuropsychiatric
      disorder. Previous studies have reported that children with ADHD exhibit deficits
      of adaptive function and insufficient motor ability. The objective of this study
      was to investigate the association between adaptive function and motor ability in
      children with ADHD compared with a group of normal children. The study group
      included 25 children with ADHD (19 boys and 6 girls), aged from 4.6 years to 8.6
      years (mean+/-standard deviation, 6.5+/-1.2). A group of 24 children without ADHD
      (normal children) were selected to match the children with ADHD on age and
      gender. The Movement Assessment Battery for Children, which includes three
      subtests, was used to assess the motor ability of the children of both groups.
      The Chinese version of Adaptive Behavior Scales, which consists of 12 life
      domains, was used to assess adaptive function of the children with ADHD. Compared
      with the normal children, children with ADHD exhibited poorer motor ability on
      all the three subtests of motor assessment. In the ADHD group, nine (36%)
      children had significant motor impairments and seven (28%) were borderline cases.
      A total of 10 (40%) children with ADHD had definite adaptive problems in one or
      more adaptive domains. With statistically controlling of IQ for the ADHD group,
      those children with impaired motor ability had significantly poorer behaviors in
      the adaptive domain of home living (p=0.035). Moreover, children with ADHD who
      had severely impaired manual dexterity performed worse than the control group in
      the adaptive domains of home living (r=-0.47, p=0.018), socialization (r=-0.49,
      p=0.013), and self-direction (r=-0.41, p=0.040). In addition, children with
      poorer ball skills had worse home living behavior (r=-0.56, p=0.003). Children
      who had more impaired balance exhibited poorer performance in social behavior (r=
      0.41, p=0.040). This study found significant correlation between motor ability
      and adaptive function in children with ADHD, especially in their adaptive domains
      of home living, socialization, and self-direction. In clinical settings,
      identification of motor difficulties may have important implications for the
      understanding of relative factors in effective management of the adaptive
      dysfunction in children with ADHD.

PMID- 21943818
TI  - Transient hyperammonemia associated with postictal state in generalized
      convulsion.
AB  - Previous studies revealed that transient hyperammonemia was noted after
      generalized convulsion. This study was undertaken to analyze the association
      between postictal state and serum ammonia levels. Adult patients presenting to
      the emergency department with seizures were included. Serum ammonia and other
      blood tests were compared between patients with full recovery of consciousness
      after generalized convulsion and those who had not completely regained
      consciousness. Patients who had not completely regained consciousness (7 of 7,
      100%) had higher rate (p=0.035) of hyperammonemia compared with patients who had
      fully regained consciousness (4 of 10, 40%) and higher level of serum ammonia
      (246 +/- 96 MUg/dL vs. 102 +/- 99 MUg/dL, p=0.006). All patients who showed
      postictal consciousness level impairment on arrival at the emergency department
      had elevated serum ammonia at that time. Transient hyperammonemia is associated
      with postictal confusion.

PMID- 21943819
TI  - Relationship between remaining teeth and self-rated chewing ability among
      population aged 45 years or older in Kaohsiung City, Taiwan.
AB  - The purposes of this study were to (1) examine the relationship between the
      number of various types of healthy remaining natural teeth at different sites and
      self-rated chewing ability and (2) evaluate the relationship between the number
      of functional tooth units (FTUs), comprising functional natural teeth (FNT) or
      fixed prostheses, and self-rated chewing ability. A sample of 296 adults (122 men
      and 174 women), aged 45 years or older (average age, 56.6+/-9.7), were recruited
      from seven dental clinics in Kaohsiung City. Dental information on the number and
      status of remaining teeth was obtained through examination by trained and
      calibrated dentists. Self-assessment of chewing ability (masticatory score) was
      evaluated with a self-administered questionnaire. Results showed that increased
      age is associated with a greater likelihood of difficulty in chewing. To avoid
      chewing difficulty, at least 24.7 FNT, 13.3 posterior-FNT, 8.1 units of natural
      tooth-FTUs, or 9.6 units of fixed tooth-FTUs must remain. Age and the number of
      healthy remaining teeth, including natural teeth and fixed prostheses, are key
      factors in chewing ability. Given that aging is unavoidable, the preservation of
      healthy remaining teeth plays a relatively important role in the maintenance of
      chewing ability among middle-aged and elderly people.

PMID- 21943821
TI  - Pneumothorax in a female with renal angiomyolipoma.
AB  - Spontaneous pneumothorax occurs less in females than in males, in contrast to the
      relatively more commonly and incidentally found renal angiomyolipoma (AML). We
      report a renal AML in a 23-year-old female patient, which presented as right
      palpable abdominal mass. This renal tumor was removed owing to enlargement and
      internal hemorrhage and AML was proved by pathological examination. Three years
      later, she experienced a life-threatening spontaneous tension pneumothorax and
      pulmonary lymphangioleiomyomatosis (LAM), which was diagnosed by chest computed
      tomography. Clinically, she did not have tuberous sclerosis. Pulmonary LAM and
      renal AML are related lesions and both of these proliferative lesions occur in
      sporadic patients without family history and at much higher frequency in patients
      with tuberous sclerosis. Because of the nonspecific symptoms and high rate of
      complications, we should consider the possibility of LAM in patients diagnosed
      with AML. The association between renal AML and pulmonary LAM is reviewed.

PMID- 21943820
TI  - Complicated Candida parapsilosis peritonitis on peritoneal dialysis in a neonate
      with renal failure because of bilateral adrenal abscesses.
AB  - We present a full-term female infant with a difficult delivery course complicated
      with Escherichia coli sepsis and bilateral adrenal abscesses. She developed renal
      failure and received peritoneal dialysis. Peritonitis of Candida parapsilosis
      developed later. The infant was successfully treated with hemofiltration and a
      combination of antifungal agents.

PMID- 21943822
TI  - Traumatic subdural hematoma in the lumbar spine.
AB  - Traumatic spinal subdural hematoma is rare and its mechanism remains unclear.
      This intervention describes a patient with mental retardation who was suffering
      from back pain and progressive weakness of the lower limbs following a traffic
      accident. Magnetic resonance imaging of the spine revealed a lumbar subdural
      lesion. Hematoma was identified in the spinal subdural space during an operation.
      The muscle power of both lower limbs recovered to normal after surgery. The
      isolated traumatic spinal subdural hematoma was not associated with intracranial
      subdural hemorrhage. A spinal subdural hematoma should be considered in the
      differential diagnosis of spinal cord compression, especially for patients who
      have sustained spinal trauma. Emergency surgical decompression is usually the
      optimal treatment for a spinal subdural hematoma with acute deterioration and
      severe neurological deficits.

PMID- 21943823
TI  - Identification of the bleomycin hydrolase gene as a methylated tumor suppressor
      gene in hepatocellular carcinoma using a novel triple-combination array method.
AB  - In the present study, we sought to identify novel suppressor genes of
      hepatocellular carcinoma (HCC) using our newly designed triple-combination array.
      Using this method, the bleomycin hydrolase gene (BLMH) was detected as a
      candidate suppressor gene. We found that 28 of 48 (58.3%) tumor tissues showed
      BLMH promoter hypermethylation, and its expression level was significantly
      reduced in tumor tissues (P=0.001). The present study suggests that our new
      method can detect novel genes of interest and that BLMH is a suppressor gene in
      HCC.

PMID- 21943824
TI  - Preparation of camptothecin-loaded PCEC microspheres for the treatment of
      colorectal peritoneal carcinomatosis and tumor growth in mice.
AB  - The aim of this study was to prepare PCL-PEG-PCL (PCEC) microspheres to protect
      camptothecin from hydrolysis, to extend its release time and to enhance its
      treatment efficacy on colorectal peritoneal carcinomatosis and tumor growth in
      mice. Camptothecin (CPT)-loaded PCL-PEG-PCL (PCEC) microspheres were prepared by
      oil-in-water emulsion solvent evaporation method. The particle size,
      morphological characteristics, encapsulation efficiency, in vitro drug release
      studies and in vitro cytotoxicity of CPT-loaded PCEC microspheres have been
      investigated. In vivo studies were carried out on Balb/c male mice bearing
      colorectal peritoneal carcinomatosis. CPT-loaded PCEC microspheres were applied
      to abdominal cavity of mice once a week. Free CPT was used as a positive control.
      On 14th day of treatment, mice were sacrificed and antitumor activities of CPT
      loaded PCEC microspheres were evaluated. Compared with control group, a
      significant decrease in the number of tumor nodes was observed in group treated
      with CPT-loaded PCEC microspheres. Immunohistochemistry staining of tumor tissues
      with CD34 revealed that MVD positive cells were significantly reduced in CPT
      loaded PCEC microspheres treated group in contrast to other groups (P<0.05). The
      CPT-loaded PCEC microspheres were considered potentially useful to treat the
      abdominal metastases of colon carcinoma.

PMID- 21943825
TI  - Inactivation of Rac1 reduces Trastuzumab resistance in PTEN deficient and insulin
      like growth factor I receptor overexpressing human breast cancer SKBR3 cells.
AB  - Drug resistance remains to be a big challenge in applying anti-HER2 monoclonal
      antibody Trastuzumab for treating breast cancer with HER2 overexpression.
      Amplification of insulin-like growth factor I receptor (IGF-IR) and deletion of
      tumor suppressor phosphatase and tensin homolog (PTEN) are implicated in
      Trastuzumab resistance, however, the underlying mechanisms have not been clearly
      defined. Activation of Rac1, a member of Rho GTPase family, is capable of causing
      cytoskeleton reorganization, regulating gene expression and promoting cell
      proliferation. To investigate the mechanism of Trastuzumab resistance, PTEN
      knockdown and IGF-IR overexpressing stable cell lines were generated in HER2
      overexpression human breast cancer SKBR3 cells. Rac1 was highly activated in PTEN
      deficient and IGF-IR overexpressing Trastuzumab-resistant cells in a HER2
      independent manner. Inactivation of Rac1 by using a Rac1 inhibitor NSC23766 or
      siRNA knocking down the expression of Tiam1, a guanine nucleotide exchange factor
      for Rac, significantly reduced Trastuzumab resistance in SKBR3 cells. Inhibition
      of Rac1 had no effect on the levels of phosphor-HER2 and phosphor-Akt, but
      significantly decreased the levels of cyclin D1 in Trastuzumab-resistant cells.
      Inhibition of Akt with an Akt inhibitor also significantly reduced Trastuzumab
      resistance. However, simultaneous inhibition of both Rac1 and Akt resulted in a
      significantly more decrease of Trastuzumab resistance than inactivation of Rac1
      or Akt alone. These results suggest that Rac1 activation is critically involved
      in Trastuzumab resistance caused by PTEN deletion or IGF-IR overexpression.
      Simultaneous inhibition of Rac1 and Akt may represent a promising strategy in
      reducing Trastuzumab resistance in HER2 overexpression breast cancer.

PMID- 21943826
TI  - Gammaherpesvirus gene expression and DNA synthesis are facilitated by viral
      protein kinase and histone variant H2AX.
AB  - Gammaherpesvirus protein kinases are an attractive therapeutic target as they
      support lytic replication and latency. Via an unknown mechanism these kinases
      enhance expression of select viral genes and DNA synthesis. Importantly, the
      kinase phenotypes have not been examined in primary cell types. Mouse
      gammaherpesvirus-68 (MHV68) protein kinase orf36 activates the DNA damage
      response (DDR) and facilitates lytic replication in primary macrophages.
      Significantly, H2AX, a DDR component and putative orf36 substrate, enhances MHV68
      replication. Here we report that orf36 facilitated expression of RTA, an
      immediate early MHV68 gene, and DNA synthesis during de novo infection of primary
      macrophages. H2AX expression supported efficient RTA transcription and
      phosphorylated H2AX associated with RTA promoter. Furthermore, viral DNA
      synthesis was attenuated in H2AX-deficient macrophages, suggesting that the DDR
      system was exploited throughout the replication cycle. The interactions between a
      cancer-associated gammaherpesvirus and host tumor suppressor system have
      important implications for the pathogenesis of gammaherpesvirus infection.

PMID- 21943827
TI  - Selection of rhinovirus 1A variants adapted for growth in mouse lung epithelial
      cells.
AB  - Rhinoviruses (RVs) are picornaviruses that are causative agents of the majority
      of upper respiratory tract infections, or "common colds," in humans. RVs infect
      both the upper and lower respiratory tract, and in addition to the common cold
      may also cause pneumonia, complications in patients with chronic lung diseases
      such as cystic fibrosis, and asthma exacerbations. Convenient animal models are
      not available to study the pathogenesis of rhinovirus-induced illness. Rhinovirus
      RV1A replicates poorly in mouse cells; variants with improved replication were
      selected by serial passage through mouse embryonic fibroblasts and mouse lung
      epithelial cells. Adaptation for improved growth in mouse cells was mediated by
      amino acid changes in the RV1a non-structural protein 3A. Mouse cell-adapted RV1A
      was capable of productively infecting mice in which the airway was subjected to
      chemical permeabilization. A mouse model for RV infection will permit studies of
      RV pathogenesis and may identify targets for therapeutic intervention.

PMID- 21943828
TI  - A preoperative education intervention to reduce anxiety and improve recovery
      among Chinese cardiac patients: a randomized controlled trial.
AB  - BACKGROUND: Patients awaiting cardiac surgery typically experience significant
      physical and psychological stress. However, although there is evidence that
      preoperative education interventions can lead to positive postoperative outcomes
      for surgical patients in general, less is known about the effectiveness among
      patients undergoing cardiac surgery, especially Chinese cardiac patients.
      OBJECTIVES: To determine whether a preoperative education intervention designed
      for Chinese cardiac patients can reduce anxiety and improve recovery. DESIGN:
      Randomized controlled trial. SETTINGS: Cardiac surgical wards of two public
      hospitals in Luoyang, China. METHODS: 153 adult patients undergoing cardiac
      surgery were randomized into the trial, 77 to a usual care control group and 76
      to preoperative education group comprising usual care plus an information leaflet
      and verbal advice. Measurement was conducted before randomization and at seven
      days following surgery. The primary outcome was change in anxiety measured by the
      Hospital Anxiety and Depression Scale (HADS). Secondary outcomes were change in
      depression (HADS), change in pain as measured by subscales of the Brief Pain
      Inventory-short form (BPI-sf), length of Intensive Care Unit stay and
      postoperative hospital stay. RESULTS: Of 153 participants randomized, 135 (88.2%)
      completed the trial. Participants who received preoperative education experienced
      a greater decrease in anxiety score (mean difference -3.6 points, 95% confidence
      interval -4.62 to -2.57; P<0.001) and a greater decrease in depression score
      (mean difference -2.1 points, 95% CI -3.19 to -0.92; P<0.001) compared with those
      who did not. There was no difference between groups in average pain, current
      pain, and interference in general activity, mood and walking ability. Patients
      randomized to the preoperative education group reported less interference from
      pain in sleeping (mean difference -0.9 points, 95% CI -1.63 to -0.16; P=0.02).
      There was some evidence to suggest a reduced number of hours spent in the
      Intensive Care Unit among preoperative education patients (P=0.05) but no
      difference in length of postoperative hospital stay (P=0.17). CONCLUSIONS: This
      form of preoperative education is effective in reducing anxiety and depression
      among Chinese cardiac surgery patients. Based upon existing evidence and
      international practice, preoperative education should be incorporated into
      routine practice to prepare Chinese cardiac patients for surgery.

PMID- 21943831
TI  - Factors affecting nursing students' knowledge of HIV/AIDS in Singapore.

PMID- 21943829
TI  - Treatment of tuberculosis: timely or accurately?

PMID- 21943832
TI  - Relative frequency of health care-associated pathogens by infection site at a
      university hospital from 1980 to 2008.
AB  - BACKGROUND: We describe the relative frequency of health care-associated
      pathogens by infection site over 29 years using hospital-wide surveillance data
      from a large academic hospital. METHODS: Comprehensive hospital-wide surveillance
      was provided by trained infection preventionists using Centers for Disease
      Control and Prevention definitions. Five 5-year blocks and one 4-year block were
      created for each site: bloodstream infections (BSI), urinary tract infections
      (UTI), respiratory tract infections (RTI), and surgical site infections (SSI).
      The blocks of relative frequency of health care-associated pathogens were
      compared by chi(2) analysis, and trends for each pathogen were estimated by
      regression analysis. RESULTS: At least 1 pathogen was isolated from 28,208
      (83.5%) of 33,797 health care-associated infections (HAI). Staphylococcus aureus,
      coagulase-negative staphylococci (CoNS), Enterococcus species, and Clostridium
      difficile and other anaerobes significantly increased, whereas Escherichia coli,
      Pseudomonas aeruginosa, Klebsiella species, Enterobacter species, and other
      streptococci significantly decreased in the relative proportion of pathogens
      during the study period. By infection site, results showed significant increasing
      trends of S aureus in UTI, RTI, and SSI; CoNS in BSI and SSI; Candida in SSI; and
      Enterococcus in BSI and UTI. CONCLUSION: Significant changes in relative
      frequency of health care-associated pathogens by infection site occurred over the
      29-year period. These findings have implications for implementation of infection
      prevention strategies.

PMID- 21943830
TI  - Incidence and modifiable risk factors of surveillance of surgical site infections
      in Egypt: a prospective study.
AB  - BACKGROUND: Surgical site infections (SSIs) contribute significantly to patient
      morbidity and mortality and exhaust health care system resources. The main
      objectives of the study were to describe the incidence rates of SSIs among
      patients undergoing urologic or cardiothoracic surgeries, the associated risk
      factors, and the common causative etiologies found at Alexandria University
      Hospital in Egypt. METHODS: A prospective active surveillance study for patients
      undergoing urologic and cardiothoracic surgeries was implemented from July 2009
      to December 2010. Patients were inspected daily for developing SSIs and with a 30
      day postoperative follow-up. Wound swabs were obtained from patients who had
      clinical signs suggestive of infection. Swabs were cultured for bacterial
      identification and tested for antimicrobial sensitivity. Standard Centers for
      Disease Control and Prevention National Health Safety Network case definitions
      were used. RESULTS: SSIs occurred in 187 (17%) of patients with complete follow
      up (n = 1,062), of which 106 (57%) occurred in-hospital and 81 (43%) occurred
      after discharge. Higher SSI rates were observed in cardiothoracic surgeries
      (23.3%), compared with urologic surgeries (9%) (P < .001). A stepwise logistic
      model identified an increased risk of SSI for those who underwent cardiothoracic
      surgeries (odds ratio [OR], 4.7; 95% confidence interval [CI], 2.2-11.1), those
      aged >45 years (OR, 2.32; 95% CI, 1.35-4.01), increased duration of hospital stay
      before (OR, 1.03; 95% CI, 1.01-1.05) and after (OR, 1.07; 95% CI, 1.04-1.09)
      surgery, antibiotics <=24 hours before surgery (OR, 2.54; 95% CI, 1.63-3.94), and
      dirty wounds (OR, 4.09; 95% CI, 1.60-10.43). CONCLUSIONS: Measures to reduce the
      high rates of SSI need to be instituted through a multidisciplinary effort
      including infection control education and specific SSI prevention activities at
      Alexandria University Hospital.

PMID- 21943833
TI  - Global precedence effect in audition and vision: evidence for similar cognitive
      styles across modalities.
AB  - This study aimed to provide evidence for a Global Precedence Effect (GPE) in both
      vision and audition modalities. In order to parallel Navon's paradigm, a novel
      auditory task was designed in which hierarchical auditory stimuli were used to
      involve local and global processing. Participants were asked to process auditory
      and visual hierarchical patterns at the local or global level. In both
      modalities, a global-over-local advantage and a global interference on local
      processing were found. The other compelling result is a significant correlation
      between these effects across modalities. Evidence that the same participants
      exhibit similar processing style across modalities strongly supports the idea of
      a cognitive style to process information and common processing principle in
      perception.

PMID- 21943834
TI  - Suspected zoonotic transmission of rotavirus group A in Danish adults.
AB  - Group A rotaviruses infect humans and a variety of animals. In July 2006 a rare
      rotavirus strain with G8P[14] specificity was identified in the stool samples of
      two adult patients with diarrheoa, who lived in the same geographical area in
      Denmark. Nucleotide sequences of the VP7, VP4, VP6, and NSP4 genes of the
      identified strains were identical. Phylogenetic analyses showed that both Danish
      G8P[14] strains clustered with rotaviruses of animal, mainly, bovine and caprine,
      origin. The high genetic relatedness to animal rotaviruses and the atypical
      epidemiological features suggest that these human G8P[14] strains were acquired
      through direct zoonotic transmission events.

PMID- 21943836
TI  - Induced sputum microbiology in confirming pulmonary tuberculosis in children.

PMID- 21943837
TI  - Analysing policy transfer: perspectives for operational research.
AB  - Policy transfer occurs regularly. In essence, a strategy developed elsewhere is
      taken up and applied in another policy context. Yet what precisely is policy
      transfer and, more importantly, under what conditions does it occur? This paper
      describes policy transfer and addresses  three main questions, exploring what
      perspectives of policy transfer might contribute to operational research (OR)
      efforts. First, what facilitates the transfer of OR results into policy and
      practice? Second, what facilitates effective lesson-drawing about OR results and
      processes between  and within countries? And third, what would increase the
      amount of OR being carried out by low- and middle-income countries and used to
      inform policy and practice at local and global levels? Mexico's adoption and
      adaptation of the DOTS strategy is used here as an example  of policy transfer.
      Policy transfer is relevant to all countries, levels and arenas of people,
      institutions and organisations involved in health. With a more systematic
      analysis of learning and policy processes, OR policy and practice outcomes could
      be improved at all levels, from local to  global. Policy transfer offers theory
      and concepts for analysing OR from a new perspective. The present paper proposes
      a model of the policy transfer process for qualitative research use.
      Comprehensive policy transfer research, given its length, complexity and need for
      qualitative researchers,  should not be envisaged for all OR projects. All OR
      projects could, however, incorporate some concepts and practical tools inspired
      from this model. This should help to plan, evaluate and improve OR processes and
      the resulting changes in policy and practice.

PMID- 21943835
TI  - Management of MDR-TB household contacts: how difficult is it to climb the
      mountain?

PMID- 21943840
TI  - Household contact investigation of multidrug-resistant and extensively drug
      resistant tuberculosis in a high HIV prevalence setting.
AB  - SETTING: Multidrug-resistant (MDR) and extensively drug-resistant (XDR)
      tuberculosis (TB) are now a nationwide epidemic in South Africa. Epidemiological
      data suggest nosocomial transmission as the primary route of spread; however,
      transmission among household contacts has not yet been  investigated. OBJECTIVE:
      To determine the incidence rates of MDR- and XDR-TB among household contacts of
      MDR- and XDR-TB index cases diagnosed between January 2005 and September 2008 in
      a high human immunodeficiency virus prevalence setting. DESIGN: Prospective,
      observational study evaluating  adult household contacts for active TB by culture
      and drug susceptibility testing at index case diagnosis and again 1 year later.
      Outcomes were incidence and time to diagnosis of MDR- and XDR-TB. RESULTS: A
      total of 1766 contacts of 221 MDR-TB and 287 XDR-TB index cases were screened. Of
      793 contacts of MDR-TB index cases, 14 (1.8%) were diagnosed with MDR-TB
      (incidence 1765/100 000); 19 (2.0%) of 973 XDR-TB contacts had XDR-TB (incidence
      1952/100 000). Median time to diagnosis of household cases was 70 days
      (interquartile range 57-89). CONCLUSION: Incidence  rates of MDR- and XDR-TB
      among household contacts were extremely high, with most secondary cases occurring
      shortly after the diagnosis of the index case. Active case finding of drug
      resistant TB is a high-yield public health activity and must be a priority, as
      early diagnosis may stem further  disease spread and improve survival.

PMID- 21943842
TI  - Tuberculosis infection in foreign-born children: a screening survey based on skin
      and blood testing.
AB  - This study, carried out in a low tuberculosis (TB) prevalence country with high
      immigration rates from high TB prevalence countries, deals with the interferon
      gamma release assay, QuantiFERON(r)-TB Gold In-Tube, for the diagnosis of latent
      TB infection (LTBI) in foreign-born children.  The results of our study highlight
      the potential advantages and concerns of using a blood test for diagnosing LTBI
      in a 'two-step' strategy in foreign-born children.

PMID- 21943841
TI  - Tuberculin skin test and QuantiFERON(r) assay in young children investigated for
      tuberculosis in South Africa.
AB  - SETTING: Although the literature on interferon-gamma release assays on
      tuberculosis (TB) in children has increased, data pertaining to young children
      remain relatively limited. OBJECTIVE: To compare results from the tuberculin skin
      test (TST) and the QuantiFERON(r)-TB Gold In-Tube  assay (QFT) in children aged
      <3 years investigated for TB disease. DESIGN: TB suspects were evaluated by
      medical history and examination, TST, QFT, chest radiography, induced sputum and
      gastric washings for smear and culture for Mycobacterium tuberculosis. RESULTS: A
      total  of 400 children were enrolled. Among 397 children with both test results,
      68 (17%) were QFT-positive and 72 (18%) were TST-positive (>=10 mm). Agreement
      between the tests was excellent (94%, kappa = 0.79, 95%CI 0.69-0.89). TB disease
      was diagnosed in 52/397 (13%) participants:  3 definite, 35 probable and 14
      possible TB. QFT sensitivity and specificity for TB disease were respectively 38%
      and 81%. TST sensitivity and specificity were respectively 35% and 84%.
      CONCLUSION: While TST and QFT had excellent concordance in this population, both
      tests had much lower  sensitivity for TB disease than has been reported for other
      age groups. Our results suggested equivalent performance of QFT and TST in the
      diagnosis of TB disease in young children in a high-burden setting.

PMID- 21943838
TI  - 2010: the year in review, part I.

PMID- 21943843
TI  - Sputum induction for microbiological diagnosis of childhood pulmonary
      tuberculosis in a community setting.
AB  - SETTING: Sputum induction has increasingly enabled microbiological confirmation
      of pulmonary tuberculosis (PTB) in hospitalised children, but it has not been
      evaluated in a community setting. OBJECTIVE: To investigate the yield,
      feasibility and safety of sputum induction for the  diagnosis of TB in children
      in a primary health care facility. DESIGN: A prospective study in a primary
      health care clinic in South Africa from April 2007 to June 2009. Consecutive
      children with clinically suspected PTB, with a household adult PTB contact or
      human immunodeficiency virus  infected with respiratory symptoms were enrolled.
      History, clinical examination, tuberculin skin test and chest X-ray results were
      recorded. Two sequential induced sputum specimens were obtained for smear and
      culture. RESULTS: A total of 270 children were enrolled (median age 38 months); 
      sputum induction was successful in 269 (99%); 65 (24%) children were clinically
      diagnosed, of whom 11 (16.9%) were microbiologically confirmed. An additional 18
      children not clinically diagnosed had microbiological confirmation of PTB and
      were placed on TB treatment thereafter, increasing  the diagnostic yield by
      21.6%, from 65 to 83 cases. Sputum induction procedures were well tolerated; no
      major adverse events occurred. CONCLUSION: Sputum induction is feasible and safe
      in a community setting. Sputum induction was useful for making a microbiological
      diagnosis, increasing  the number of children diagnosed and treated for PTB.

PMID- 21943844
TI  - Abnormal thyroid function tests in children on ethionamide treatment.
AB  - Ethionamide (ETH) treatment may cause hypothyroidism. Clinical data, serum
      thyroid stimulating hormone (TSH) and free thyroxine (fT4) levels were
      retrospectively assessed in 137 children receiving anti-tuberculosis treatment
      including ETH. Abnormal thyroid function tests (TFTs) were  recorded in 79 (58%)
      children: elevated serum TSH and suppressed fT4 (n = 30), isolated elevated serum
      TSH (n = 20), isolated low serum fT4 (n = 28) and isolated low TSH (n = 1). The
      risk for biochemical hypothyroidism was higher for  children on regimens
      including para-aminosalicylic acid and in human immunodeficiency virus infected
      children. TFT abnormalities are frequent in children on ETH and are mainly due to
      primary hypothyroidism or euthyroid sick syndrome.

PMID- 21943846
TI  - Nationwide survey of anti-tuberculosis drug resistance in Mongolia.
AB  - BACKGROUND: Drug-resistant tuberculosis (TB) has emerged as an obstacle to
      effective TB control. SETTING: The eight district and 21 province TB dispensaries
      and the two TB hospitals comprising the diagnostic centers for TB in Mongolia.
      METHODS: To investigate drug resistance levels  among new and retreated TB cases.
      Specifically, we determined the prevalence of resistance to rifampin,
      streptomycin, isoniazid and ethambutol among TB patients with and without prior
      anti-tuberculosis treatment. RESULTS: A total of 850 patients (74.1% of eligible
      and 78.0% of patients  with a specimen) had Mycobacterium tuberculosis isolated
      and are the subject of this analysis. Of these, 200 had a history of prior
      treatment and 650 did not. Any multidrug resistance was found in 7.5% (95%CI 5.9
      9.5), with respectively 27.5% (95%CI 21.8-34.1) and 1.4% (95%CI  0.7-1.6) of
      patients with and without prior history of treatment. CONCLUSIONS: The most
      conspicuous finding in our survey was the relatively low prevalence of multidrug
      resistance among patients without a history of prior treatment, as compared to
      very high prevalence among previously  treated patients. This suggests that
      retreatment is deficient and poses a threat to continued transmission, which has
      not yet manifested itself among new patients.

PMID- 21943845
TI  - Early antiretroviral treatment reduces risk of bacille Calmette-Guerin immune
      reconstitution adenitis.
AB  - SETTING: Two centres in Soweto and Cape Town, South Africa. OBJECTIVE: To assess
      the effects of timing of initiation of antiretroviral treatment (ART) and other
      factors on the risk of bacille Calmette-Guerin (BCG) related regional adenitis
      due to immune reconstitution inflammatory  syndrome (BCG-IRIS) in human
      immunodeficiency virus (HIV) infected infants. DESIGN: HIV-infected infants aged
      6-12 weeks with CD4 count >=25% enrolled in the Children with HIV Early
      Antiretroviral Therapy (CHER) Trial received early (before 12 weeks) or deferred
      (after immunological  or clinical progression) ART; infants with CD4 count <25%
      all received early ART. All received BCG vaccination after birth. Reactogenicity
      to BCG was assessed prospectively during routine study follow-up. RESULTS: Of 369
      infants, 32 (8.7%) developed BCG-IRIS within 6 months of starting  ART, 28 (88%)
      within 2 months after ART initiation. Of the 32 cases, 30 (93.8%) had HIV-1 RNA >
      750 000 copies/ml at initiation. Incidence of BCG-IRIS was 10.9 and 54.3 per 100
      person-years (py) among infants with CD4 count >=25% at enrolment receiving early
      (at median age 7.4  weeks) vs. deferred (23.2 weeks) ART, respectively (HR 0.24,
      95%CI 0.11-0.53, P < 0.001). Infants with CD4 count <25% receiving early ART had
      intermediate incidence (41.7/100 py). Low CD4 counts and high HIV-1 RNA at
      initiation were the strongest independent risk factors  for BCG-IRIS.
      CONCLUSIONS: Early ART initiation before immunological and/or clinical
      progression substantially reduces the risk of BCG-IRIS regional adenitis.

PMID- 21943839
TI  - Tuberculosis in household contacts of multidrug-resistant tuberculosis patients.
AB  - SETTING: The burden of tuberculosis (TB) disease among household contacts of
      multidrug-resistant TB (MDR-TB) patients is poorly understood and might represent
      a target for transmission-interrupting interventions. DESIGN: This retrospective
      cohort study, conducted in Lima, Peru, from  June to September 2008, estimated
      the incidence of TB disease among household contacts of MDR-TB patients in 358
      households. RESULTS: Of 2112 household contacts in 80 households (22% of
      households), 108 (5%) developed TB disease during the study, giving an incidence
      rate of 2360 per 100 000  contact follow-up years for each of the first 3 years
      after exposure. Drug susceptibility tests (DST) were available for 50 diseased
      contacts, of whom 36 (80%) had MDR-TB. Forty-two pairs of index-contact DSTs were
      available, among which the contact had an identical or less resistant phenotype 
      than the index case in 27 pairs. Multivariate Cox regression demonstrated that
      male contacts (hazard ratio [HR] 2.8, P < 0.05), with previous TB disease (HR
      20.7, P < 0.001) and with associated (non-human immunodeficiency virus)
      comorbidities (HR 11.2, P < 0.001)  were more likely to develop TB. CONCLUSION:
      The high percentage of diseased household contacts highlights an opportunity for
      household-level interventions to prevent transmission, whether or not these cases
      were all attributable to the index case.

PMID- 21943847
TI  - Field assessment of the direct nitrate reductase assay for rapid detection of
      multidrug-resistant tuberculosis in Honduras.
AB  - SETTING: The national TB reference laboratory and four health care units
      connected to the national laboratory network in Honduras, Central America.
      OBJECTIVE: To evaluate the performance of the direct nitrate reductase assay
      (NRA) for rapid, low-cost detection of multidrug-resistant  tuberculosis (MDR-TB)
      in a resource-limited setting. DESIGN: Consecutive smear-positive samples (n =
      185) were prospectively analysed with NRA and compared to the proportion method
      on Lowenstein Jensen medium (PM-LJ) to detect resistance to isoniazid (INH) and
      rifampicin  (RMP). RESULTS: The NRA sensitivity, specificity, positive and
      negative predictive values for INH and RMP were respectively 100%, 99%, 91%, 100%
      and 80%, 100%, 100%, 99%. Good agreement was observed between NRA and PM-LJ
      (kappa > 0.8). CONCLUSION: The direct NRA is a reliable alternative  for rapid
      and low-cost identification of MDR-TB cases in resource-limited settings.

PMID- 21943848
TI  - Evaluation of a simple loop-mediated isothermal amplification test kit for the
      diagnosis of tuberculosis.
AB  - OBJECTIVE: A new loop-mediated isothermal amplification (LAMP) test kit,
      including a simple DNA extraction device for the detection of Mycobacterium
      tuberculosis complex, was developed for commercial use and evaluated for its
      usefulness in diagnosing tuberculosis (TB). DESIGN: The LAMP test was performed
      using untreated and N-acetyl-L-cysteine (NALC) NaOH-treated sputum specimen. The
      efficiency of the kit was compared with other conventional laboratory
      examinations, including other nucleic acid amplification (NAA) tests. RESULTS:
      The sensitivity of LAMP  using raw sputum (direct LAMP) in smear- and culture
      positive specimens was 98.2% (95%CI 94.9-99.4), while the sensitivity in smear
      negative, culture-positive specimens was 55.6% (95%CI 43.4-68.0). The diagnostic
      sensitivity of direct LAMP for the diagnosis of individuals with  TB was 88.2%
      (95%CI 81.4-92.7). The sensitivity values of direct LAMP were slightly, but not
      statistically significantly lower than those of Cobas Amplicor MTB and TRC Rapid
      MTB, while the sensitivity of the LAMP test using NALC-NaOH treated sputum was
      significantly lower than other  NAA tests (P < 0.05) for smear-negative, culture
      positive specimens. The new commercial version of the LAMP kit was easy to handle
      and yielded results within 1 h of receiving sputum specimens. CONCLUSIONS: This
      test is considered a promising diagnostic tool for TB, even for peripheral 
      laboratories with limited equipment, such as those in developing countries.

PMID- 21943849
TI  - Mycobacterium tuberculosis testing practices in hospital, commercial and state
      laboratories in the New England states.
AB  - SETTING: The mycobacterial laboratory is assuming an increasingly important role
      in tuberculosis (TB) control in the United States today. OBJECTIVE: To assess
      mycobacterial laboratory capacity and practices in the New England states, USA.
      DESIGN: We surveyed 143 hospital and commercial  laboratories and five of the six
      state public health laboratories in New England that offer testing services for
      Mycobacterium tuberculosis. The survey captured information on types of services
      offered and volume of testing, use of state laboratories for testing, and
      promptness of reporting  results to TB control programs. RESULTS: State
      laboratories perform the majority of testing services, particularly for more
      specialized tests. All state laboratories surveyed perform species identification
      of acid-fast isolates, culture and first-line drug susceptibility testing. Less
      than  20% of hospital and commercial laboratories offer these services, and 78.6%
      of hospitals and commercial laboratories refer specimens to state laboratories
      for culture. CONCLUSION: Surveys of M. tuberculosis testing capacities in a
      region can help decision makers ensure maintenance  of essential services.
      Hospital and commercial laboratories with lower testing volume might increase
      efficiency by referring more specimens to state laboratories. State health
      departments might consider organizing regional laboratory service networks to
      monitor the provision of services, improve  efficiency and oversee quality
      improvement initiatives.

PMID- 21943850
TI  - Cost-effectiveness analysis of targeted and sequential screening strategies for
      latent tuberculosis.
AB  - SETTING: No cost-effectiveness studies of testing for latent tuberculosis
      infection have incorporated both targeted testing and the use of interferon-gamma
      release assays (IGRAs) in heterogeneous populations. OBJECTIVE: To examine the
      cost-effectiveness of universal vs. targeted  and sequential testing strategies
      and the use of tuberculin skin testing (TST) vs. IGRAs. DESIGN: Using a decision
      analytic model, incremental cost-effectiveness ratios were calculated in 2009
      among nine potential strategies for screening recruits. A societal perspective
      was taken over  a 20-year analytic horizon, discounting future costs at 3%
      annually. Sensitivity analyses were conducted to determine how changes in
      assumptions affected the estimates. RESULTS: Targeted strategies cost over US$250
      000 per case prevented, whereas universal testing strategies  cost over US$700
      000 per incremental case prevented in base case and most sensitivity analyses.
      CONCLUSION: Targeted testing offered the best value in this population, although
      it was still relatively expensive compared to no testing. Sequential testing with
      both TST and IGRAs  provided a poor incremental value compared to targeted and
      universal testing strategies. Targeted testing using TST was slightly more cost
      effective than targeted testing using either QuantiFERON(r)-TB Gold In-Tube or T
      SPOT(r).TB, but these estimates were very sensitive to changes  in model
      assumptions.

PMID- 21943851
TI  - Delays in seeking treatment for symptomatic tuberculosis in Sabah, East Malaysia:
      factors for patient delay.
AB  - SETTING: The state of Sabah contributes one third of the tuberculosis (TB) cases
      in Malaysia. OBJECTIVE: To collect information on factors that affect the time
      period from the onset of symptoms to first contact with health care providers,
      whether private or government. DESIGN: A cross-sectional study using a pre-tested
      questionnaire was conducted among 296 newly registered smear-positive TB patients
      in 10 districts in Sabah. Univariable and multivariable analyses were used to
      determine which risk factors were associated with patient delay (>30 days) and
      'extreme'  patient delay (>90 days). RESULTS: The percentage of patients who
      sought treatment after 30 and 90 days was respectively 51.8% (95%CI 45.7-57.9)
      and 23.5% (95%CI 18.6-29.0). The strongest factors associated with patient delay
      and 'extreme' patient delay was when  the first choice for treatment was a non
      government health facility and in 30-39-year-olds. 'Extreme' patient delay was
      also weakly associated, among other factors, with comorbidity and livestock
      ownership. CONCLUSION: Delay and extreme delay in seeking treatment were  more
      common when the usual first treatment choice was a non-government health
      facility. Continuous health education on TB aimed at raising awareness and
      correcting misconceptions is needed, particularly among those who use non
      government facilities.

PMID- 21943852
TI  - Serum trace metal and ceruloplasmin variability in individuals treated for
      pulmonary tuberculosis.
AB  - SETTING: Investigation of trace metal behaviour during the treatment of active
      pulmonary tuberculosis (PTB) patients residing in Romania. OBJECTIVE: To assess,
      follow and identify serum iron (Fe), copper (Cu) and zinc (Zn) levels in patients
      diagnosed and treated for active PTB. DESIGN: Chemical and statistical analysis
      of various biochemical parameters in 47 subjects diagnosed with active PTB and
      170 healthy Romanian residents. RESULTS: Copper and ceruloplasmin levels were
      increased in patients with active PTB compared to the control group (P < 0.01),
      while  the serum Zn level was significantly lower than in healthy subjects (P <
      0.01) or within the normal range. The present study shows that there is a
      significant correlation between serum Cu concentrations and ceruloplasmin.
      CONCLUSIONS: This study provides preliminary evidence that  Zn and Fe
      redistribution is operating as a primary host defence mechanism to reduce the
      availability of metals for microbial metabolism during infection. The study also
      calls attention to the fact that anti-tuberculosis treatment is sufficient to
      enhance the concentration of the antioxidant  species (Cu and ceruloplasmin). The
      data obtained suggest that serum Cu, Zn and Cu/Zn levels may serve as indirect
      pointers in the diagnosis of a disease but they cannot be considered as specific
      markers for TB.

PMID- 21943854
TI  - Epidemiological analysis of Mycobacterium tuberculosis strains isolated in Lodz,
      Poland.
AB  - BACKGROUND: Mycobacterium tuberculosis is one of the most dangerous human
      pathogens. Molecular typing of M. tuberculosis has allowed better control of
      tuberculosis and, among other benefits, identification of genetic lineages among
      strains. OBJECTIVE: To test the potential  of polymerase chain reaction (PCR)
      based methods for the epidemiological study of M. tuberculosis strains isolated
      from patients residing in a single city. DESIGN: We performed spoligotyping,
      mycobacterial interspersed repetitive units-variable number of tandem repeats
      (MIRU-VNTR)  typing and insertion sequence (IS) 6110 restriction fragment length
      polymorphism (RFLP) analyses of 234 clinical strains of M. tuberculosis collected
      over 2 years from the Polish city of Lodz. RESULTS: Spoligotyping analysis
      revealed 84 spoligotypes with a shared international  type and 50 unique
      spoligotypes. Subtyping via 15- and 19-loci MIRU-VNTR analyses revealed 154
      patterns with 117 unique profiles, and 159 patterns with 126 unique profiles,
      respectively. Spoligotyping combined with MIRU-VNTR 15- and 19 loci analyses
      revealed 132 and 146 unique profiles, respectively.  Overall, 96 strains
      clustered via MIRU-VNTR typing were used in IS6110-RFLP analysis. Complete
      congruence of patterns revealed by PCR-based methods was noted for 40 strains, of
      which 36 were isolated from epidemiologically linked patients. CONCLUSION: The
      combination of 15-loci MIRU-VNTR  typing with spoligotyping is useful for primary
      analysis of M. tuberculosis strains; however, additional use of MIRU 23 should be
      considered. Strains clustered by PCR-based methods should be further analysed by
      IS6110-RFLP typing.

PMID- 21943853
TI  - Association between the interleukin-18 promoter polymorphism and pulmonary
      tuberculosis in a Korean population.
AB  - OBJECTIVE: To examine the role of the -667G/T, -618A/C and -148G/C single
      nucleotide polymorphisms in the promoter region of the human interleukin (IL) 18
      gene in the development of pulmonary tuberculosis (PTB), and its radiographic
      characteristics and severity. DESIGN: Differences in the allele and genotype
      distributions of the -667G/T, -618A/C, and -148G/C polymorphisms between 251
      patients with PTB and 225 healthy controls, between patients with single- and
      multilobe involvement, and between patients with and without cavities were
      explored.  Serum IL-18 levels were measured using an enzyme-linked immunosorbent
      assay. RESULTS: The -148G/G genotype was more common in patients with cavities
      than in those without (82.8% vs. 70.9%, P = 0.04), but an analogous trend was not
      observed for the -667G/T and -618A/C  genotypes. However, there were no
      significant differences in allele and genotype distributions between patients
      with PTB and healthy controls, or between patients with single- and multilobe
      involvement (P > 0.05). Serum IL-18 levels were higher in patients with cavities
      (P  = 0.01) and in patients with the -148G/G genotype (P = 0.02). CONCLUSION:
      Considering serum IL-18 levels, the -148G/G genotype is associated with a
      cavitary formation of PTB rather than its development.

PMID- 21943855
TI  - Paid employment in subjects with and without chronic obstructive pulmonary
      disease in five Latin American cities: the PLATINO study.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a costly condition
      that frequently causes permanent work disabilities. Little information exists
      regarding the impact of COPD on work force participation and the indirect costs
      of the disease in developing countries. OBJECTIVE: To examine the frequency of
      paid employment and factors influencing it in a Latin-American population-based
      study. METHODS: Post-bronchodilator FEV(1)/FVC < 0.70 (forced expiratory volume
      in 1 s/forced vital capacity) was used to define COPD. Information regarding paid
      work  was assessed by the question 'At any time in the past year, have you worked
      for payment?' RESULTS: Interviews were conducted with 5571 subjects; 5314 (759
      COPD and 4554 non-COPD) subjects underwent spirometry. Among the COPD subjects,
      41.8% reported having paid work vs.  57.1% of non-COPD (P < 0.0001). The number
      of months with paid work was reduced in COPD patients (10.5 +/- 0.17 vs. 10.9 +/-
      0.06, P < 0.05). The main factors associated with having paid work in COPD
      patients were male sex (OR 0.33, 95%CI 0.23-0.47), higher  education level (OR
      1.05, 95%CI 1.01-1.09) and younger age (OR 0.90, 95%CI 0.88-0.92). COPD was not a
      significant contributor to employment (OR 0.83, 95%CI 0.69-1.00, P = 0.054) in
      the entire population. CONCLUSIONS: Although the proportion of persons with  paid
      work is lower in COPD, having COPD appears not to have a significant impact on
      obtaining paid employment in the overall population of developing countries.

PMID- 21943856
TI  - Carotid atherosclerosis in patients with untreated chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with
      systemic inflammation. OBJECTIVE: To evaluate carotid artery intima-media
      thickness (IMT), high sensitivity C-reactive protein (hsCRP) and their
      correlation in newly diagnosed untreated patients with COPD. DESIGN: Post
      bronchodilator spirometry, carotid artery IMT and blood tests were measured in
      patients with COPD (COPD group). Age, sex, body mass index, smoking status and
      smoking amount were compared with matched healthy subjects (non-COPD group).
      Participants taking medications and/or with a history  of hypertension, diabetes
      mellitus, dyslipidaemia, COPD or cardiovascular disease were excluded. RESULTS: A
      total of 126 patients (COPD group 42, non-COPD group 84) were enrolled. The IMT
      and hsCRP of the COPD group were significantly higher than in the non-COPD group
      (P < 0.05).  The decrease in the forced expiratory volume in 1 second/forced
      vital capacity (FEV(1)/FVC) ratio and FEV(1) was significantly correlated with an
      increase in the hsCRP and IMT (P < 0.05); there was no correlation between the
      IMT and hsCRP (P = 0.152). CONCLUSION: In newly diagnosed untreated patients with
      COPD, the carotid artery IMT and hsCRP were significantly higher than in healthy
      subjects. These findings suggest that systemic inflammation may play a potential
      role in preclinical atherosclerosis in COPD.

PMID- 21943862
TI  - GeneXpert(r) MTB/RIF for rapid detection of Mycobacterium tuberculosis in
      pulmonary and extra-pulmonary samples.

PMID- 21943859
TI  - No rebound in tuberculosis in the United States in 2010.

PMID- 21943860
TI  - Pre-screening with GeneXpert(r) MTB/RIF may increase use of isoniazid preventive
      therapy in antiretroviral programmes.

PMID- 21943863
TI  - Hepatotoxicity in the treatment of tuberculosis using moxifloxacin-containing
      regimens.

PMID- 21943857
TI  - Reactivation or re-infection?

PMID- 21943864
TI  - No time to be complacent with the performance of tuberculosis control activities
      in tribal areas of India.

PMID- 21943868
TI  - Eight initiatives that misleadingly lower ventilator-associated pneumonia rates.

PMID- 21943867
TI  - A rare storm in a psychiatric ward: thyroid storm.
AB  - We present the case of a previously healthy man in whom acute psychosis masked
      the major symptomatology of thyroid storm. This patient highlights the importance
      of taking into consideration a life-threatening condition, thyroid storm, in the
      differential diagnosis of acute psychosis, even in the absence of a history of
      thyrotoxicosis.

PMID- 21943869
TI  - Immunogenetics of HIV and HIV associated tuberculosis.
AB  - Tuberculosis (TB) is the frequent major opportunistic infection in HIV-infected
      patients, and is the leading cause of mortality among HIV-infected patients.
      Genetic susceptibility to TB in HIV negative subjects is well documented. Since
      coinfections can influence the way in which immune system respond to different
      pathogens, genetic susceptibility to TB in HIV patients might also change.
      Studies from India and other parts of the world have shown that genetic
      susceptibility to TB is influenced by HIV infection. In the present review, we
      emphasize the role of genetic factors in determining susceptibility to HIV
      infection, disease progression and development of TB in HIV-infected patients.
      Polymorphisms in human leukocyte antigen (HLA), MBL2, CD209, vitamin D receptor,
      cytokine, chemokine and chemokine receptor genes have been shown to be associated
      with development of TB in HIV patients. However, the results are inconclusive and
      larger well-defined studies with precise clinical data are required to validate
      these associations. Apart from candidate gene approach, genome-wide association
      studies are also needed to unravel the unknown or to establish the previously
      reported genetic associations with HIV associated TB. Despite the preliminary
      status of the reported associations, it is becoming clear that susceptibility to
      development of TB in HIV patients is influenced by both environmental and genetic
      components. Understanding the genetic and immunologic factors that influence
      susceptibility to TB in HIV patients could lead to novel insights for vaccine
      development as well as diagnostic advances to target treatment to those who are
      at risk for developing active disease.

PMID- 21943870
TI  - Informatics resources for tuberculosis--towards drug discovery.
AB  - Integration of biological data on gene sequence, genome annotation, gene
      expression, metabolic pathways, protein structure, drug target prioritization and
      selection, has resulted in several online bioinformatics databases and tools for
      Mycobacterium tuberculosis. Alongside there has been a growth in the list of
      cheminformatics databases for small molecules and tools to facilitate drug
      discovery. In spite of these efforts there is a noticeable lag in the drug
      discovery process which is an urgent need in the case of emerging and re-emerging
      infectious diseases. For example, more than 25 online databases are available
      freely for tuberculosis and yet these resources have not been exploited
      optimally. Informatics-centered drug discovery based on the integration and
      analysis of both bioinformatics and cheminformatics data could fill in the gap
      and help to accelerate the process of drug discovery. This article aims to review
      the current standing of developments in tuberculosis-bioinformatics and highlight
      areas where integration of existing resources could lead to acceleration of drug
      discovery against tuberculosis. Such an approach could be adapted for other
      diseases as well.

PMID- 21943871
TI  - Chondroitin sulfate-g-poly(epsilon-caprolactone) co-polymer aggregates as
      potential targeting drug carriers.
AB  - The aim of this study is to delineate the effect of various amounts of
      hydrophobic polycaprolactone (PCL) grafted onto three different degrees of
      methacrylated chondroitin sulfate (CSMA) on chemical-physical properties. The co
      polymers were prepared by reacting the modified PCL and the hydrophilic CSMA via
      a radical reaction (CSMA-PCL). The effect of degree of methacrylation of CSMA and
      feed ratio between CSMA and PCL on compositions and critical micelle
      concentrations was systematically studied. The PCL composition of the CSMA-PCL
      was characterized by (1)H-NMR and FT-IR. The hydrodynamic diameters and
      morphologies of CSMA-PCL micelles were studied by DLS and TEM. Critical micelle
      concentrations were determined using pyrene as a probe. Taking one of the CSMA
      PCL micelles as an example, a cancer-mediated ligand, folic acid, was linked to
      the surface. The cellular uptake of the folic acid-linked CSMA-PCL in folate
      receptor-overexpressing KB cells was studied by confocal laser scanning
      microscopy and flow cytometry. 

PMID- 21943865
TI  - What is the role of autofluorescence bronchoscopy in screening lung cancer among
      silicotic subjects?

PMID- 21943872
TI  - Prostate-specific antigen surveillance among men with clinically localized
      prostate cancer who do not receive initial treatment.
AB  - OBJECTIVE: To describe the use and determinants of prostate-specific antigen
      (PSA) surveillance in a population-based cohort. PSA measurements are an
      important component of surveillance for men with clinically localized prostate
      cancer who do not receive initial treatment. METHODS: Using the linked
      Surveillance, Epidemiology, and End Results-Medicare program, we evaluated 7145
      men, aged 65-84 years, who had been diagnosed from 1997 to 2002 with American
      Joint Committee on Cancer, 6th edition, Stage T1-T2, Gleason score <=7 prostate
      cancer and received expectant management. For all patients, the Medicare claims
      were observed until a secondary cancer treatment event, death, or December 31,
      2006. We performed multivariable logistic regression analysis to examine the
      relationship between the primary outcome of annual PSA surveillance and the
      patient, clinical, and demographic characteristics. RESULTS: Of the men with
      localized Gleason score <=7 prostate cancer who did not receive initial
      treatment, 39% underwent at least annual PSA measurement. On multivariable
      logistic regression analysis, annual PSA surveillance was positively associated
      with older age (75-84 vs 65-74 years, odds ratio [OR] 1.37, 95% confidence
      interval [CI] 1.23-1.52), more comorbidities (OR 3.38, 95% CI 2.91-3.93), and
      residence in a neighborhood with a greater median income (OR 1.81, 95% CI 1.46
      2.25). A lower likelihood of annual PSA surveillance was associated with black
      race (OR 0.55, 95% CI 0.45-0.67). CONCLUSION: Most men with localized prostate
      cancer who forgo initial treatment do not receive annual PSA surveillance.
      Additional research is necessary to clarify the benefits and harm of increased
      surveillance among older men and those with medical comorbidities.

PMID- 21943873
TI  - The association between circulating endothelial progenitor cells and coronary
      collateral formation.
AB  - AIM: We investigated the relationship between coronary collateral formation and
      circulating endothelial progenitor cells (EPC) in patients undergoing coronary
      angiography. METHODS AND RESULTS: Circulating CD133(+)/34(+) and CD34(+)/KDR(+)
      EPCs were determined in 68 patients (normal coronary vessels in 24 patients and
      coronary artery disease (CAD) in 44 patients) (age: 58.7 +/- 10.1, 64.7% male).
      Circulating EPCs were higher among patients with normal coronary vessels compared
      to patients with CAD for CD133(+)/34(+) (p < 0.05) and CD34(+)/KDR(+) cells (p <
      0.05). The number of EPCs were significantly greater in patients with good
      coronary collateral formation (p < 0.05). EPC count was independent predictor for
      coronary collateral formation after adjustment for other cardiovascular risk
      factors and extent of CAD (p = 0.037). CONCLUSION: In patients with severe
      coronary stenosis, those with increased circulating EPCs had better collateral
      formation compared to those with lower EPC counts. Our findings implicate that in
      addition to presence of critical stenosis, intact response of bone marrow is
      necessary for collateral formation in CAD.

PMID- 21943875
TI  - [Melanoma and pregnancy].

PMID- 21943874
TI  - Impact of wound blush as an angiographic end point of endovascular therapy for
      patients with critical limb ischemia.
AB  - OBJECTIVES: Several reports have been published of the acceptable patency and
      limb salvage rates after infrapopliteal interventions for the treatment of
      critical limb ischemia (CLI). However, the optimal angiographic end point of
      endovascular therapy (EVT) remains unclear. This study assessed the relationship
      between the appearance of wound blush as an angiographic end point and the limb
      salvage rate in patients with CLI. METHODS: "Wound blush" was defined as contrast
      opacification of the vessels around the wound in digital subtraction angiograms
      obtained immediately after EVT through the catheter introduced into the popliteal
      artery. We analyzed the data of 77 consecutive patients (93 limbs) with ischemic
      ulcerations, classified as Rutherford category 5 or 6, who underwent EVT without
      bypass surgery. Patients were divided into two groups depending on whether wound
      blush was seen in the angiogram obtained immediately after the procedure. The
      freedom from amputation rate was compared between the two groups. RESULTS: The
      overall limb salvage rate was 81.7%. The limb salvage rate was significantly
      higher in the wound blush-positive group than in the wound blush-negative group
      and remained so for at least 3 years after the EVT (96.4% vs 56.8%, P < .001).
      CONCLUSIONS: Presence of wound blush after EVT is associated with higher skin
      perfusion pressure, both of which are associated with higher rates of limb
      salvage. Wound blush as an angiographic end point in EVT may be a novel predictor
      of limb salvage in patients with CLI.

PMID- 21943876
TI  - [Follicular lymphoma with paraneoplastic autoimmune multiorgan syndrome].

PMID- 21943879
TI  - [Network and epidemiologic information in nephrology: Kidney report 2009].

PMID- 21943877
TI  - [Early detection of anal intraepithelial neoplasia in high-risk patients].

PMID- 21943878
TI  - [Program for major outpatient surgery in dermatology].

PMID- 21943881
TI  - Simulation of Eisenmenger syndrome with ventricular septal defect using
      equivalent electronic system.
AB  - BACKGROUND: In this study, we aim to investigate the simulation of the
      cardiovascular system using an electronic circuit model under normal and
      pathological conditions, especially the Eisenmenger syndrome. METHODS AND
      RESULTS: The Eisenmenger syndrome includes a congenital communication between the
      systemic and pulmonary circulation, with resultant pulmonary arterial
      hypertension and right-to-left reversal of flow through the defect. When
      pulmonary vascular resistance exceeds systemic vascular resistance, it results in
      hypoxaemia and cyanosis. The Westkessel model including Resistor-Inductance
      Capacitance pi-segments was chosen in order to simulate both systemic and
      pulmonary circulation. The left and right heart are represented by trapezoidal
      shape stiffness for better simulation results. The Eisenmenger syndrome is
      simulated using a resistance (septal resistance) connected between the left
      ventricle and right ventricle points of the model. Matlab(r) is used for the
      model implementation. In this model, although there is a remarkable increase in
      the pulmonary artery pressure and right ventricle pressure, left ventricle
      pressure, aortic pressure, aortic flow, and pulmonary compliance decrease in the
      Eisenmenger syndrome. In addition, left-to-right septal flow reversed in these
      diseases. CONCLUSION: Our model is effective and available for simulating normal
      cardiac conditions and cardiovascular diseases, especially the Eisenmenger
      syndrome.

PMID- 21943880
TI  - [Network and epidemiologic information in nephrology: Kidney report 2009].
AB  - In 2009, 8,560 patients with end-stage renal disease living in 20 regions
      (Alsace, Auvergne, Bourgogne, Bretagne, Centre, Champagne-Ardenne, Corse, Haute
      Normandie, Ile de France, la Reunion, Languedoc-Roussillon, Limousin, Lorraine,
      Midi- Pyrenees, Nord-Pas de Calais, Pays de Loire, Picardie, Poitou- Charentes,
      Provence-Alpes Cote d'Azur and Rhone-Alpes) covering 57 million inhabitants (89%
      of the French population), started renal replacement therapy (dialysis or
      preemptive graft): median age was 70,2 years ; 3,4% had a preemptive graft. The
      overall crude annual incidence rate of renal replacement therapy for end-stage
      renal disease was 150 per million population (pmp), with significant differences
      in sex and age-adjusted incidence across regions (99 to 389 pmh). At initiation,
      more than one patient out of two had at least one cardiovascular disease and 41%
      diabetes (92% Type 2 non-insulin-dependent diabetes). On December 31, 2009,
      33,558 patients living in the above 20 regions were on dialysis : median age was
      70,5 years. On December 31, 2009, 29,181 patients were living with a functioning
      graft : median age was 54,8 years. In these 20 regions, the overall prevalence of
      dialysis was 588 pmp, that of renal graft, 510 pmp and the overall rate of renal
      replacement therapy for end stage renal disease, 1,098 pmp with significant
      differences in age-adjusted prevalence across regions (809 to 2,709 pmh). In the
      2002-2009 cohort of 43,433 incident patients, the overall one-year survival rate
      was 83%, 45% at 6 years. Survival decreased with age, but remained above 50% at 2
      years in patients older than 75 at RRT initiation. Among the 8,688 new patients
      starting dialysis in 2009 in 23 regions (the 20 regions mentioned above, plus
      Aquitaine, Pays de Loire and Guadeloupe), 5% had a BMI lower than 18,5 kg/m2 and
      20% a BMI higher than 30. At initiation, 66% had a haemoglobin value lower than
      11 g/l and 10% an albumin value lower than 25 g/l. The first haemodialysis was
      started in emergency in 33 % of the patients and with a catheter in 54 %. On
      December 31, 2009, 7 % treated in the dialysis units of the 22 regions (the 20
      regions mentioned above, plus Aquitaine and Pays de Loire) received peritoneal
      dialysis, of which 40% were treated with automated peritoneal dialysis. 95% of
      the patients on haemodialysis had 3 sessions per week, with a median duration of
      4 hours. In the 2002-2009 cohort of incident patients in 18 regions under 60
      years, the probability to be at least once on the waiting list for a renal graft
      is 50% at 15,6 months. In 2009, 2,750 patients received a renal graft. On
      December 31, 2009, 7,272 patients were on the waiting list for a renal graft in
      the transplantation centres of the 22 regions. The analysis of the flows between
      treatments indicates that the proportion of the transplanted patients among RTT
      patients is increasing. The main source for transplantation is the outcenter
      patients.

PMID- 21943882
TI  - A potential approach for monitoring drinking water quality from groundwater
      systems using organic matter fluorescence as an early warning for contamination
      events.
AB  - The fluorescence characteristics of natural organic matter in a groundwater based
      drinking water supply plant were studied with the aim of applying it as a
      technique to identify contamination of the water supply. Excitation-emission
      matrices were measured and modeled using parallel factor analysis (PARAFAC) and
      used to identify which wavelengths provide the optimal signal for monitoring
      contamination events. The fluorescence was characterized by four components:
      three humic-like and one amino acid-like. The results revealed that the relative
      amounts of two of the humic-like components were very stable within the supply
      plant and distribution net and changed in a predictable fashion depending on
      which wells were supplying the water. A third humic-like component and an amino
      acid-like component did not differ between wells. Laboratory contamination
      experiments with wastewater revealed that combined they could be used as an
      indicator of microbial contamination. Their fluorescence spectra did not overlap
      with the other components and therefore the raw broadband fluorescence at the
      wavelengths specific to their fluorescence could be used to detect contamination.
      Contamination could be detected at levels equivalent to the addition of 60 MUg
      C/L in drinking water with a TOC concentration of 3.3 mg C/L. The results of this
      study suggest that these types of drinking water systems, which are vulnerable to
      microbial contamination due to the lack of disinfectant treatment, can be easily
      monitored using online organic matter fluorescence as an early warning system to
      prompt further intensive sampling and appropriate corrective measures.

PMID- 21943883
TI  - Photodegradation of psychiatric pharmaceuticals in aquatic environments--kinetics
      and photodegradation products.
AB  - Benzodiazepines are widely consumed psychiatric pharmaceuticals which are
      frequently detected in the environment. The environmental persistence and fate of
      these pharmaceuticals as well as their degradation products is of high relevance
      and it is, yet, scarcely elucidated. In this study, the relevance of
      photodegradation processes on the environmental persistence of four
      benzodiazepines (oxazepam, diazepam, lorazepam and alprazolam) was investigated.
      Benzodiazepines were irradiated under simulated solar irradiation and direct and
      indirect (together with three different fractions of humic substances)
      photodegradation kinetics were determined. Lorazepam was shown to be quickly
      photodegradated by direct solar radiation, with a half-life time lower than one
      summer sunny day. On the contrary, oxazepam, diazepam and alprazolam showed to be
      highly resistant to photodegradation with half-life times of 4, 7 and 228 summer
      sunny days, respectively. Apparent indirect and direct photodegradation rates are
      of the same order of magnitude. However, humic acids were consistently
      responsible for a decrease in the photodegradation rates while fulvic acids and
      XAD4 fraction caused an enhancement of the photodegradation. Overall, the results
      highlight that photodegradation might not be an efficient pathway to prevent the
      aquatic environmental accumulation of oxazepam, diazepam and alprazolam. Also,
      nineteen direct photodegradation products were identified by electrospray mass
      spectrometry, the majority of which are newly identified photoproducts. This
      identification is crucial to a more complete understanding of the environmental
      impact of benzodiazepines in aquatic systems.

PMID- 21943885
TI  - A full scale worm reactor for efficient sludge reduction by predation in a
      wastewater treatment plant.
AB  - Sludge predation can be an effective solution to reduce sludge production at a
      wastewater treatment plant. Oligochaete worms are the natural consumers of
      biomass in benthic layers in ecosystems. In this study the results of secondary
      sludge degradation by the aquatic Oligochaete worm Aulophorus furcatus in a 125
      m(3) reactor and further sludge conversion in an anaerobic tank are presented.
      The system was operated over a period of 4 years at WWTP Wolvega, the Netherlands
      and was fed with secondary sludge from a low loaded activated sludge process. It
      was possible to maintain a stable and active population of the aquatic worm
      species A. furcatus during the full period. Under optimal conditions a sludge
      conversion of 150-200 kg TSS/d or 1.2-1.6 kg TSS/m(3)/d was established in the
      worm reactor. The worms grew as a biofilm on carrier material in the reactor. The
      surface specific conversion rate reached 140-180 g TSS/m(2)d and the worm biomass
      specific conversion rate was 0.5-1 g TSS sludge/g dry weight worms per day. The
      sludge reduction under optimal conditions in the worm reactor was 30-40%. The
      degradation by worms was an order of magnitude larger than the endogenous
      conversion rate of the secondary sludge. Effluent sludge from the worm reactor
      was stored in an anaerobic tank where methanogenic processes became apparent. It
      appeared that besides reducing the sludge amount, the worms' activity increased
      anaerobic digestibility, allowing for future optimisation of the total system by
      maximising sludge reduction and methane formation. In the whole system it was
      possible to reduce the amount of sludge by at least 65% on TSS basis. This is a
      much better total conversion than reported for anaerobic biodegradability of
      secondary sludge of 20-30% efficiency in terms of TSS reduction.

PMID- 21943884
TI  - Characterization of bromate-reducing bacterial isolates and their potential for
      drinking water treatment.
AB  - The objective of the current study was to isolate and characterize several
      bromate-reducing bacteria and to examine their potential for bioaugmentation to a
      drinking water treatment process. Fifteen bromate-reducing bacteria were isolated
      from three sources. According to 16S rRNA gene sequencing, the bromate-reducing
      bacteria are phylogenetically diverse, representing the Actinobacteria,
      Bacteroidetes, Firmicutes, and alpha-, beta-, and gamma-Proteobacteria. The broad
      diversity of bromate-reducing bacteria suggests the widespread capability for
      microbial bromate reduction. While the cometabolism of bromate via nitrate
      reductase and (per)chlorate reductase has been postulated, five of our bromate
      reducing isolates were unable to reduce nitrate or perchlorate. This suggests
      that a bromate-specific reduction pathway might exist in some microorganisms.
      Bioaugmentation of activated carbon filters with eight of the bromate-reducing
      isolates did not significantly decrease start-up time or increase bromate removal
      as compared to control filters. To optimize bromate reduction in a biological
      drinking water treatment process, the predominant mechanism of bromate reduction
      (i.e., cometabolic or respiratory) needs to be assessed so that appropriate
      measures can be taken to improve bromate removal.

PMID- 21943886
TI  - The effect of pH on N2O production under aerobic conditions in a partial
      nitritation system.
AB  - Ammonia-oxidising bacteria (AOB) are a major contributor to nitrous oxide (N(2)O)
      emissions during nitrogen transformation. N(2)O production was observed under
      both anoxic and aerobic conditions in a lab-scale partial nitritation system
      operated as a sequencing batch reactor (SBR). The system achieved 55 +/- 5%
      conversion of the 1g NH(4)(+)-N/L contained in a synthetic anaerobic digester
      liquor to nitrite. The N(2)O emission factor was 1.0 +/- 0.1% of the ammonium
      converted. pH was shown to have a major impact on the N(2)O production rate of
      the AOB enriched culture. In the investigated pH range of 6.0-8.5, the specific
      N(2)O production was the lowest between pH 6.0 and 7.0 at a rate of 0.15 +/- 0.01
      mg N(2)O-N/h/g VSS, but increased with pH to a maximum of 0.53 +/- 0.04 mg N(2)O
      N/h/g VSS at pH 8.0. The same trend was also observed for the specific ammonium
      oxidation rate (AOR) with the maximum AOR reached at pH 8.0. A linear
      relationship between the N(2)O production rate and AOR was observed suggesting
      that increased ammonium oxidation activity may have promoted N(2)O production.
      The N(2)O production rate was constant across free ammonia (FA) and free nitrous
      acid (FNA) concentrations of 5-78 mg NH(3)-N/L and 0.15-4.6 mg HNO(2)-N/L,
      respectively, indicating that the observed pH effect was not due to changes in FA
      or FNA concentrations.

PMID- 21943887
TI  - Donepezil dosing strategies: pharmacokinetic considerations.
AB  - Donepezil (Aricept) is a cholinesterase inhibitor approved for the treatment of
      Alzheimer's disease. Immediate release formulations of 5- and 10-mg tablets were
      approved by the Food and Drug Administration in the United States in 1996. In
      July 2010, the Food and Drug Administration approved a 23-mg sustained release
      (SR) formulation. The SR formulation may provide additional benefit to patients
      receiving 10 mg daily but the incidence of adverse reactions is increased. We
      derived plasma concentration profiles for higher dose immediate-release
      formulations (15 mg once daily, 10 mg twice daily, and 20 mg once daily) and for
      the profile anticipated to result from the 23-mg SR formulation. Our model
      predicts similar steady-state concentration profiles for 10 mg twice daily, 20 mg
      once daily, and 23 mg SR once daily. This provides the theoretical basis for
      incremental immediate release dose escalation to minimize the emergence of
      adverse reactions and the potential to offer a cost-effective alternative to the
      SR formulation with currently approved generic immediate release formulations.

PMID- 21943889
TI  - Systems biology left and right.
AB  - Systems biology has come of age. In most scientifically active countries,
      significant research programs are funded. Various scientific journals, standards,
      repositories, and Web sites are devoted to the topic. Systems biology has spun
      off new subdisciplines such as synthetic biology and systems medicine. There are
      training courses at the M.Sc. and Ph.D. level at various Universities. And
      various industries are engaging systems biology in their R&D. Systems biology has
      also developed numerous new methodologies. This chapter attempts to organize
      these methodologies from the perspectives of the unique aims of systems biology,
      and by comparing with one of its parents, molecular biology.

PMID- 21943888
TI  - Histological correlate of a cardiac magnetic resonance imaged microvascular
      obstruction in a porcine model of ischemia-reperfusion.
AB  - BACKGROUND: Microvascular obstruction after reperfusion therapy of acute
      myocardial infarction is reported as an adverse promoter of left ventricular
      remodeling and is an important target to prevent deterioration into heart
      failure. In this study, we illustrate the early onset of a magnetic resonance
      imaged microvascular obstruction in a porcine model of acute myocardial
      infarction with the exact histological correlate. METHODS: Occlusion of the left
      anterior descending coronary artery followed by 3-h reperfusion was performed in
      10 pigs. Microvascular obstruction was assessed by contrast-enhanced magnetic
      resonance imaging (MRI). After sacrifice, serial sectioned slices of the hearts
      matching the MRI were stained with Triphenyl tetrazolium chloride (TTC). Biopsies
      were fixed, embedded in paraffin, and stained for hematoxylin-eosin. RESULTS:
      Microvascular obstruction was defined with MRI as a hypoenhanced no-reflow area
      within the hyperenhanced infarct region. Erythrocyte plugging was consistently
      observed in the no-reflow area and was completely absent in the adjacent
      hyperenhanced infarct region. CONCLUSION: This model of acute ischemia
      reperfusion contributes to the histological comprehension of contrast-enhanced
      MRI during the early stages of myocardial infarction.

PMID- 21943890
TI  - Mass spectrometry in systems biology an introduction.
AB  - The qualitative detection, quantification, and structural characterization of
      analytes in biological systems are important requirements for objectives to be
      fulfilled in systems biology research. One analytical tool applied to a multitude
      of systems biology studies is mass spectrometry, particularly for the study of
      proteins and metabolites. Here, the role of mass spectrometry in systems biology
      will be assessed, the advantages and disadvantages discussed, and the instrument
      configurations available described. Finally, general applications will be briefly
      reviewed.

PMID- 21943892
TI  - Absorption spectroscopy.
AB  - Absorption spectroscopy is one of the most widely used techniques employed for
      determining the concentrations of absorbing species (chromophores) in solutions.
      It is a nondestructive technique which biologists and biochemists and now systems
      biologists use to quantify the cellular components and characteristic parameters
      of functional molecules. This quantification is most relevant in the context of
      systems biology. For creating a quantitative depiction of a metabolic pathway, a
      number of parameters and variables are important and these need to be determined
      experimentally. This chapter describes the UV-visible absorption spectroscopy
      used to produce experimental data for bottom-up modeling approaches of systems
      biology which uses concentrations and kinetic parameters (K(m) and V(max)) of
      enzymes of metabolic/signaling pathways, intracellular concentrations of
      metabolites and fluxes. It also briefly describes the application of this
      technique for quantification of biomolecules and investigating biomolecular
      interactions.

PMID- 21943891
TI  - High-throughput quantification of posttranslational modifications in situ by CA
      FLIM.
AB  - Signal transduction is mediated by posttranslational modifications (PTMs) of
      proteins in complex signaling networks. Quantifying PTM levels of multiple
      network components in response to a stimulus is therefore the key to understand
      how their concerted activities give rise to cellular function. We have shown that
      fluorescence lifetime imaging microscopy (FLIM) on cell arrays (CA-FLIM) provides
      a method to accurately quantify PTM levels of many proteins in situ. Herein, we
      describe the detailed protocol for CA-FLIM. Less than 2 days are needed from cell
      array preparation to data analysis, where the main limiting step is the 24h
      needed for transfection. After generating a single cell array containing 384
      spots, it can be imaged and analyzed in less than 2h.

PMID- 21943893
TI  - A strand-specific library preparation protocol for RNA sequencing.
AB  - The analysis of transcriptome, which was over the past decade based mostly on
      microarray technologies, is now being superseded by so-called next generation
      sequencing (NGS) systems that changed the way to explore entire transcriptome.
      RNA sequencing (RNA-Seq), one application of NGS, is a powerful tool, providing
      information not only about the expression level of genes but also further about
      the structure of transcripts as it enables to unequivocally identify splicing
      events, RNA editing products, and mutations in expressed coding sequences within
      a single experiment. Herein, we describe step by step the deoxy-UTP (dUTP) strand
      marking protocol [Parkhomchuk, D., Borodina, T., Amstislavskiy, V., Banaru, M.,
      Hallen, L., Krobitsch, S., Lehrach, H., Soldatov, A. (2009). Transcriptome
      analysis by strand-specific sequencing of complementary DNA. Nucleic Acids
      Res.37(18), e123], which has been recently reviewed as the leading protocol for
      strand-specific RNA-Seq library preparation [Levin, J. Z., Yassour, M., Adiconis,
      X., Nusbaum, C., Thompson, D. A., Friedman, N., Gnirke, A., Regev, A. (2009).
      Comprehensive comparative analysis of strand-specific RNA sequencing methods.
      Nat. Methods7(9), 709-715]. The procedure starts with the isolation of the polyA
      fraction (mRNA) within a pool of total RNA, followed by its fragmentation. Then
      double-stranded (ds) cDNA synthesis is performed with the incorporation of dUTP
      in the second strand. The ds cDNA fragments are further processed following a
      standard sequencing library preparation scheme tailored for the Illumina
      sequencing platform: end polishing, A-tailing, adapter ligation, and size
      selection. Prior to final amplification, the dUTP-marked strand is selectively
      degraded by Uracil-DNA-Glycosylase (UDG). The remaining strand is amplified to
      generate a cDNA library suitable for sequencing.

PMID- 21943896
TI  - Mass spectrometric-based quantitative proteomics using SILAC.
AB  - One of the main goals of comparative cell signaling analyses is the
      characterization of protein changes between different biological samples, either
      globally or by targeting specific proteins of interest. Highly accurate and
      precise strategies are thus required for the relative quantification of proteins
      extracted from two or more different cell populations. Stable isotope labeling
      with amino acids in cell culture (SILAC) is a general method for mass
      spectrometric quantitative proteomics based on metabolic incorporation of stable
      isotope-labeled amino acids into the cellular protein pool. This method has been
      applied with great success to a variety of quantitative proteomics problems aimed
      at gaining further insight into cell signaling pathways. In this chapter, we
      describe how SILAC can be used for the elucidation of cellular mechanisms,
      including temporal proteome profiling and the quantitative analysis of the extent
      of specific posttranslational modifications.

PMID- 21943894
TI  - Quantitative real-time PCR-based analysis of gene expression.
AB  - Quantitative real-time polymerase chain reaction (QRT-PCR) has become an
      extensively applied technique. It enables quantitative analyses of gene
      expression applicable to basic molecular biology, medicine, and diagnostics.
      Nowadays, it is broadly used to describe messenger RNA (mRNA) expression patterns
      and to compare the relative levels of mRNA within distinct biological samples.
      The scope of the QRT-PCR technique makes it applicable across a wide range of
      experimental conditions and allows experimental comparison between normal and
      abnormal tissue. Most importantly, this technique enables additional independent
      confirmation of microarray or next generation sequencing (NGS)-based results. An
      inherent advantage of QRT-PCR is the large dynamic range, remarkable sensitivity,
      and sequence-specificity. We provide a detailed step by step guide to the
      principles underlying a successful QRT-PCR experiment.

PMID- 21943895
TI  - Quantification of proteins and their modifications using QconCAT technology.
AB  - Building a mathematical model of a biological system requires input of
      experimental data for each networked component, ultimately generating a model
      that can be used to test scientific hypotheses. A fundamental requirement in the
      computation of these systems is that the total amount of each component can be
      specified precisely. An added level of complexity occurs because a vast number of
      protein posttranslational modifications modulate protein function. Each of these
      modified forms therefore needs to be considered as a separate system component,
      and must therefore be quantified individually. In this chapter, we describe how
      designer QconCAT proteins can be used to determine the absolute amounts of both
      the polypeptide components and their covalently modified derivatives in both
      yeast and mammalian extracts derived from living cell populations.

PMID- 21943897
TI  - Nucleic acid programmable protein array a just-in-time multiplexed protein
      expression and purification platform.
AB  - Systematic study of proteins requires the availability of thousands of proteins
      in functional format. However, traditional recombinant protein expression and
      purification methods have many drawbacks for such study at the proteome level. We
      have developed an innovative in situ protein expression and capture system,
      namely NAPPA (nucleic acid programmable protein array), where C-terminal tagged
      proteins are expressed using an in vitro expression system and efficiently
      captured/purified by antitag antibodies coprinted at each spot. The NAPPA
      technology presented in this chapter enable researchers to produce and display
      fresh proteins just in time in a multiplexed high-throughput fashion and utilize
      them for various downstream biochemical researches of interest. This platform
      could revolutionize the field of functional proteomics with it ability to produce
      thousands of spatially separated proteins in high density with narrow dynamic
      rand of protein concentrations, reproducibly and functionally.

PMID- 21943899
TI  - Protein production in Saccharomyces cerevisiae for systems biology studies.
AB  - Proteins together with metabolites, nucleic acids, lipids, and other
      intracellular molecules form biological systems that involve networks of
      functional and physical interactions. To understand these interactions and the
      many other characteristics of proteins in the context of biochemical networks and
      systems biology, research aimed at studying medium and large sets of proteins is
      required. This either involves an investigation focused on individual protein
      activities in the mixture (e.g., cell extracts) or a protein characterization in
      the isolated form. This chapter provides an overview on the currently available
      resources and strategies for isolation of proteins from Saccharomyces cerevisiae.
      The use of standardized gene expression systems is discussed, and protein
      production protocols applied to the data generation pipeline for systems biology
      are described in detail.

PMID- 21943898
TI  - Systems biology of recombinant protein production using Bacillus megaterium.
AB  - The Gram-negative bacterium Escherichia coli is the most widely used production
      host for recombinant proteins in both academia and industry. The Gram-positive
      bacterium Bacillus megaterium represents an increasingly used alternative for
      high yield intra- and extracellular protein synthesis. During the past two
      decades, multiple tools including gene expression plasmids and production strains
      have been developed. Introduction of free replicating and integrative plasmids
      into B. megaterium is possible via protoplasts transformation or
      transconjugation. Using His(6)- and StrepII affinity tags, the intra- or
      extracellular produced proteins can easily be purified in one-step procedures.
      Different gene expression systems based on the xylose controlled promoter P(xylA)
      and various phage RNA polymerase (T7, SP6, K1E) driven systems enable B.
      megaterium to produce up to 1.25g of recombinant protein per liter. Biomass
      concentrations of up to 80g/l can be achieved by high cell density cultivations
      in bioreactors. Gene knockouts and gene replacements in B. megaterium are
      possible via an optimized gene disruption system. For a safe application in
      industry, sporulation and protease-deficient as well as UV-sensitive mutants are
      available. With the help of the recently published B. megaterium genome sequence,
      it is possible to characterize bottle necks in the protein production process via
      systems biology approaches based on transcriptome, proteome, metabolome, and
      fluxome data. The bioinformatical platform (Megabac, http://www.megabac.tu-bs.de)
      integrates obtained theoretical and experimental data.

PMID- 21943900
TI  - Towards a full quantitative description of yeast metabolism a systematic approach
      for estimating the kinetic parameters of isoenzymes under in vivo like
      conditions.
AB  - In order to produce a full quantitative description of yeast metabolism, a number
      of kinetic parameters of enzymes that are important for energy metabolism must be
      determined experimentally. We aim to determine the prospective in vivo kinetic
      properties of a range of yeast-purified isoenzymes that are important in energy
      metabolism, with respect to the concentration of their substrates and products.
      This endeavor forms part of our systems biology pipeline to facilitate the
      production of bottom-up models of metabolism. Within this workflow, we implement
      an infrastructure for medium- to high-throughput determination of the kinetic
      properties of purified isoenzymes in in vivo like conditions. This includes the
      use of the KineticsWizard software for data capture and analysis. The captured
      experimental data are analyzed by the software and subsequently stored in
      appropriate repositories (MeMo-RK and SABIO-RK). While we focus initially on
      glycolysis in Saccharomyces cerevisiae, our methodology is generic and can be
      widely applied to the study of other enzymes and pathways in yeast and other
      organisms.

PMID- 21943903
TI  - Sample preparation related to the intracellular metabolome of yeast methods for
      quenching, extraction, and metabolite quantitation.
AB  - The determination of intracellular metabolite concentrations in Saccharomyces
      cerevisiae cell systems requires appropriate experimental methods to (a) collect
      cells and rapidly inhibit metabolism (quenching), (b) fracture cell walls and
      extract metabolites from within the cellular envelope(s), and (c) detect and
      quantify metabolites. A range of methods are applied for each of these processes,
      and no single method is appropriate for all metabolites. For example, the
      physicochemical diversity of metabolites, including solubility in water or
      organic solvents, is large. No single extraction solvent is appropriate for all
      metabolites reported in S. cerevisiae, and multiple solvent systems for
      extraction employing water, methanol, and chloroform at different pH are
      recommended for targeted extraction of metabolites. In this chapter, methods for
      the targeted study of organic acids present in the tricarboxylic acid cycle will
      be described. These include (a) the quenching of metabolism in batch cell
      cultures, (b) a single extraction method which provides the extraction of a wide
      diversity of metabolites, and (c) an analytical method applying gas
      chromatography-mass spectrometry for targeted analysis of six organic acids
      present in the tricarboxylic acid cycle metabolic pathway.

PMID- 21943901
TI  - Enzyme kinetics for systems biology when, why and how.
AB  - In vitro enzymatic assays of cell-free extracts offer an opportunity to assess in
      vivo enzyme concentrations. If performed under conditions that resemble the
      conditions in vivo, they may also reveal some of the capacities and properties of
      the same enzymes in vivo; we shall call this the ex vivo approach. The kinetic
      characterization of purified enzymes has yet a different utility for systems
      biology, as does the in vivo determination of enzyme activities. All these
      approaches are different, and it is becoming important that the appropriate
      approach be used for the intended purpose. Here, we therefore discuss five
      approaches to the measurement of enzyme activity in terms of the source of the
      enzyme activity, the identity of the assay medium, and the purpose of the assay.

PMID- 21943902
TI  - The use of continuous culture in systems biology investigations.
AB  - When acquiring data for systems biology studies, it is essential to perform the
      experiments in controlled and reproducible conditions. Advances in the fields of
      proteomics and metabolomics allow the quantitative analysis of the components of
      the biological cell. It is essential to include a method in the experimental
      pipeline to culture the biological system in controlled and reproducible
      conditions to facilitate the acquisition of high-quality data. The employment of
      continuous culture methods for the growth of microorganisms is an ideal tool to
      achieve these objectives. This chapter will review the continuous culture
      approaches which may be applied in such studies, outline the experimental options
      which should be considered, and describe the approach applied in the production
      of steady-state cultures of Saccharomyces cerevisiae.

PMID- 21943905
TI  - The study of mammalian metabolism through NMR-based metabolomics.
AB  - High-resolution NMR spectroscopy has been widely used to monitor metabolism
      almost since the technique's development. It is now one of the principle
      technologies used in metabolomics, to profile the metabolite compliment of a
      cell, tissue, organism, or biofluid. This chapter describes how tissue extracts
      are prepared for NMR spectroscopy and, in particular, focuses on two approaches
      based on perchloric acid and methanol/chloroform extractions. This is followed by
      a description of key NMR experiments that can be used to profile tissue extracts,
      biofluids, or intact tissues. While these NMR techniques should be optimized for
      a particular sample set, we provide some tried and tested starting parameters for
      these experiments which should allow the user to acquire good quality spectra.

PMID- 21943904
TI  - Plant metabolomics and its potential for systems biology research background
      concepts, technology, and methodology.
AB  - The "metabolome" comprises the entire complement of small molecules in a plant or
      any other organism. It represents the ultimate phenotype of cells, deduced from
      the perturbation of gene expression and the modulation of protein function, as
      well as environmental cues. Extensive advances over the past decade, regarding
      the high-throughput (HTP) nature of "omics" research, have given birth to the
      expectation that a type of "systems level" overview may soon be possible. Having
      such a global overview of the molecular organization of a plant in the context of
      a particular set of genetic or environmental conditions, be it at cell, organ, or
      whole plant level, would clearly be very powerful. Currently, we are far from
      achieving this goal; however, within our hands, plant metabolomics is an HTP and
      informative "omics" approach to both sample generation and data generation, as
      well as raw data preprocessing, statistical analysis, and biological
      interpretation. Within this chapter, we aim to describe the great attention given
      to experimental design to ensure that the correct sample set and control are
      included and to, thereby, enable reliable statistical analysis of the data. For
      as comprehensive metabolite coverage as possible, we advocate the use of
      multiparallel approaches; thus, we describe a step-by-step standardized method
      for Nuclear magnetic resonance spectroscopy, as well as discussing with reference
      to standardized methodologies the techniques of gas chromatography-time of
      flight/mass spectrometry, and liquid chromatography-mass spectrometry.

PMID- 21943906
TI  - Building a kinetic model of trehalose biosynthesis in Saccharomyces cerevisiae.
AB  - In this chapter, we describe the steps needed to create a kinetic model of a
      metabolic pathway based on kinetic data from experimental measurements and
      literature review. Our methodology is presented by utilizing the example of
      trehalose metabolism in yeast. The biology of the trehalose cycle is briefly
      reviewed and discussed.

PMID- 21943907
TI  - Sustainable model building the role of standards and biological semantics.
AB  - Systems biology models can be reused within new simulation scenarios, as parts of
      more complex models or as sources of biochemical knowledge. Reusability does not
      come by itself but has to be ensured while creating a model. Most important,
      models should be designed to remain valid in different contexts-for example, for
      different experimental conditions-and be published in a standardized and well
      documented form. Creating reusable models is worthwhile, but it requires some
      efforts when a model is developed, implemented, documented, and published.
      Minimum requirements for published systems biology models have been formulated by
      the MIRIAM initiative. Main criteria are completeness of information and
      documentation, availability of machine-readable models in standard formats, and
      semantic annotations connecting the model elements with entries in biological Web
      resources. In this chapter, we discuss the assumptions behind bottom-up modeling;
      present important standards like MIRIAM, the Systems Biology Markup Language
      (SBML), and the Systems Biology Graphical Notation (SBGN); and describe software
      tools and services for handling semantic annotations. Finally, we show how
      standards can facilitate the construction of large metabolic network models.

PMID- 21943908
TI  - From reaction networks to information flow--using modular response analysis to
      track information in signaling networks.
AB  - Even if the biochemical details of signaling networks are known, it is often hard
      to track how information flows through the network. In combination with
      experimental techniques, modular response analysis has proven useful in analyzing
      the quantitative information transfer in signal transduction networks. The
      sensitivity of a target (e.g., transcription factor, protein) to an upstream
      stimulus (e.g., growth factor) can be determined by a so-called response
      coefficient. We have used this methodology to analyze how information flows in
      networks where the details of the mechanisms in the networks are known, but
      parameters are lacking. Using a Monte Carlo approach, we apply this method to
      track the routes of information flow. More specifically, we determine whether a
      given species has no, positive or negative influence on any other species in the
      network. Surprisingly, one can uniquely determine whether a molecule activates or
      inhibits another one in more than 99% of the interactions solely from the
      topology of the reaction network. To exemplify the methodology, we briefly
      discuss three signaling networks of different complexity: (i) a Wnt signaling
      pathway model with 15 species, (ii) a MAPK signaling pathway model with 200
      species, and (iii) a large-scale signaling network of the entire cell with over
      6000 species.

PMID- 21943910
TI  - Hands-on metabolism analysis of complex biochemical networks using elementary
      flux modes.
AB  - The aim of this chapter is to discuss the basic principles and reasoning behind
      elementary flux mode analysis (EFM analysis)--an important tool for the analysis
      of metabolic networks. We begin with a short introduction into metabolic pathway
      analysis and subsequently outline in detail fundamentals of EFM analysis by way
      of a small example network. We discuss issues arising in the reconstruction of
      metabolic networks required for EFM analysis and how they can be circumvented.
      Subsequently, we analyze a more elaborate example network representing
      photosynthate metabolism. Finally, we give an overview of applications of EFM
      analysis in biotechnology and other fields and discuss issues arising when
      applying methods from metabolic pathway analysis to genome-scale metabolic
      networks.

PMID- 21943911
TI  - How to obtain true and accurate rate-values.
AB  - In metabolic flux calculations, the uptake and secretion rates (for substrate,
      O(2), CO(2), growth, (by)-products) are essential to arrive at correct calculated
      fluxes. Surprisingly, a lot of research has been published on the methods of flux
      calculations, but much less attention has been spent on the methods to obtain
      accurate and true uptake and secretion rates which are used as input. Therefore,
      this contribution focuses on.

PMID- 21943909
TI  - Whole-genome metabolic network reconstruction and constraint-based modeling.
AB  - With the advent of modern high-throughput genomics, there is a significant need
      for genome-scale analysis techniques that can assist in complex systems analysis.
      Metabolic genome-scale network reconstructions (GENREs) paired with constraint
      based modeling are an efficient method to integrate genomics, transcriptomics,
      and proteomics to conduct organism-specific analysis. This text explains key
      steps in the GENRE construction process and several methods of constraint-based
      modeling that can help elucidate basic life processes and development of disease
      treatment, bioenergy solutions, and industrial bioproduction applications.

PMID- 21943912
TI  - A practical guide to genome-scale metabolic models and their analysis.
AB  - Genome-scale metabolic reconstructions and their analysis with constraint-based
      modeling techniques have gained enormous momentum. It is a natural next step
      after sequencing of a genome, as a technique that links top-down systems biology
      analyses at genome scale with bottom-up systems biology modeling scrutiny. This
      chapter aims at (systems) biologists that have an interest in, but no extensive
      knowledge of, applying genome-scale metabolic reconstruction and modeling to
      their organism. Rather than being comprehensive--excellent and extensive reviews
      exist on every aspect of this field--we give a rather personal account on our
      experience with the process of reconstruction and modeling. First, we place
      genome-scale metabolic models in the spectrum of modeling approaches, and rather
      extensively discuss, for nonexperts, the central concept in constraint-based
      modeling: the solution space that is bounded through constraints on fluxes. We
      subsequently provide an overview of the different steps involved in metabolic
      reconstruction and modeling, pointing to aspects that we found difficult,
      important, not well enough addressed in the current reviews, or any combination
      thereof. In this way, we hope that this chapter serves as a practical guide
      through the field.

PMID- 21943913
TI  - Supply-demand analysis a framework for exploring the regulatory design of
      metabolism.
AB  - The living cell can be thought of as a collection of linked chemical factories, a
      molecular economy in which the principles of supply and demand obtain. Supply
      demand analysis is a framework for exploring and gaining an understanding of
      metabolic regulation, both theoretically and experimentally, where regulatory
      performance is measured in terms of flux control and homeostatic maintenance of
      metabolite concentrations. It is based on a metabolic control analysis of a
      supply-demand system in steady state in which the degree of flux and
      concentration control by the supply and demand blocks is related to their local
      properties, which are quantified as the elasticities of supply and demand. These
      elasticities can be visualized as the slopes of the log-log rate characteristics
      of supply and demand. Rate characteristics not only provide insight about system
      behavior around the steady state but can also be expanded to provide a view of
      the behavior of the system over a wide range of concentrations of the metabolic
      intermediate that links the supply and the demand. The theoretical and
      experimental results of supply-demand analysis paint a picture of the regulatory
      design of metabolic systems that differs radically from what can be called the
      classical view of metabolic regulation, which generally explains the role of
      regulatory mechanisms only in terms of the supply, completely ignoring the
      demand. Supply-demand analysis has recently been generalized into a computational
      tool that can be used to study the regulatory behavior of kinetic models of
      metabolic systems up to genome-scale.

PMID- 21943914
TI  - Modular kinetic analysis.
AB  - Modularization is an important strategy to tackle the study of complex biological
      systems. Modular kinetic analysis (MKA) is a quantitative method to extract
      kinetic information from such a modularized system that can be used to determine
      the control and regulatory structure of the system, and to pinpoint and quantify
      the interaction of effectors with the system. The principles of the method are
      described, and the relation with metabolic control analysis is discussed.
      Examples of application of MKA are given.

PMID- 21943915
TI  - Quantitative analysis of flux regulation through hierarchical regulation
      analysis.
AB  - Regulation analysis is a methodology that quantifies to what extent a change in
      the flux through a metabolic pathway is regulated by either gene expression or
      metabolism. Two extensions to regulation analysis were developed over the past
      years: (i) the regulation of V(max) can be dissected into the various levels of
      the gene-expression cascade, such as transcription, translation, protein
      degradation, etc. and (ii) a time-dependent version allows following flux
      regulation when cells adapt to changes in their environment. The methodology of
      the original form of regulation analysis as well as of the two extensions will be
      described in detail. In addition, we will show what is needed to apply regulation
      analysis in practice. Studies in which the different versions of regulation
      analysis were applied revealed that flux regulation was distributed over various
      processes and depended on time, enzyme, and condition of interest. In the case of
      the regulation of glycolysis in baker's yeast, it appeared, however, that cells
      that remain under respirofermentative conditions during a physiological challenge
      tend to invoke more gene-expression regulation, while a shift between
      respirofermentative and respiratory conditions invokes an important contribution
      of metabolic regulation. The complexity of the regulation observed in these
      studies raises the question what is the advantage of this highly distributed and
      condition-dependent flux regulation.

PMID- 21943916
TI  - Origins of stochastic intracellular processes and consequences for cell-to-cell
      variability and cellular survival strategies.
AB  - Quantitative analyses of the dynamics of single cells have become a powerful
      approach in current cell biology. They give us an unprecedented opportunity to
      study dynamics of molecular networks at a high level of accuracy in living single
      cells. Genetically identical cells, growing in the same environment and sharing
      the same growth history, can differ remarkably in their molecular makeup and
      physiological behaviors. The origins of this cell-to-cell variability have in
      many cases been traced to the inevitable stochasticity of molecular reactions.
      Those mechanisms can cause isogenic cells to have qualitatively different life
      histories. Many studies indicate that molecular noise can be exploited by cell
      populations to enhance survival prospects in uncertain environments. On the other
      hand, cells have evolved noise-suppression mechanisms to cope with the inevitable
      noise in their functioning so as to reduce the hazardous effects of noise. In
      this chapter, we discuss key experiments, theoretical results, and physiological
      consequences of molecular stochasticity to introduce this exciting field to a
      broader community of (systems) biologists.

PMID- 21943917
TI  - The SEEK: a platform for sharing data and models in systems biology.
AB  - Systems biology research is typically performed by multidisciplinary groups of
      scientists, often in large consortia and in distributed locations. The data
      generated in these projects tend to be heterogeneous and often involves high
      throughput "omics" analyses. Models are developed iteratively from data generated
      in the projects and from the literature. Consequently, there is a growing
      requirement for exchanging experimental data, mathematical models, and scientific
      protocols between consortium members and a necessity to record and share the
      outcomes of experiments and the links between data and models. The overall output
      of a research consortium is also a valuable commodity in its own right. The
      research and associated data and models should eventually be available to the
      whole community for reuse and future analysis. The SEEK is an open-source, Web
      based platform designed for the management and exchange of systems biology data
      and models. The SEEK was originally developed for the SysMO (systems biology of
      microorganisms) consortia, but the principles and objectives are applicable to
      any systems biology project. The SEEK provides an index of consortium resources
      and acts as gateway to other tools and services commonly used in the community.
      For example, the model simulation tool, JWS Online, has been integrated into the
      SEEK, and a plug-in to PubMed allows publications to be linked to supporting data
      and author profiles in the SEEK. The SEEK is a pragmatic solution to data
      management which encourages, but does not force, researchers to share and
      disseminate their data to community standard formats. It provides tools to assist
      with management and annotation as well as incentives and added value for
      following these recommendations. Data exchange and reuse rely on sufficient
      annotation, consistent metadata descriptions, and the use of standard exchange
      formats for models, data, and the experiments they are derived from. In this
      chapter, we present the SEEK platform, its functionalities, and the methods
      employed for lowering the barriers to adoption of standard formats. As the
      production of biological data continues to grow, in systems biology and in the
      life sciences in general, the need to record, manage, and exploit this wealth of
      information in the future is increasing. We promote the SEEK as a data and model
      management tool that can be adapted to the specific needs of a particular systems
      biology project.

PMID- 21943918
TI  - Crossing the boundaries delivering trans-disciplinary science in a disciplinary
      world.
AB  - Major research initiatives are increasingly drawing on multiple disparate
      disciplines and systems biology is a key exemplar. Trans-disciplinary research
      occurs where individual disciplinary traditions combine to create new shared
      knowledge that cannot be said to fit within the domain of any single discipline.
      Generation of new understanding of biological systems at the cell, organ, or
      organism level clearly meets these criteria, and we therefore consider systems
      biology research a truly trans-disciplinary undertaking. Aside from the
      technological challenges of combining research outcomes of the contributing
      disciplines, directing and managing the overall research program also presents a
      significant challenge. In this chapter, we discuss the challenges of and enablers
      to working across the broad range of disciplines that contribute to systems
      biology research; we discuss potential management models that may be adopted and
      the features, benefits, and drawbacks of each, introducing examples of management
      models adopted at two UK Systems Biology Centres.

PMID- 21943919
TI  - Methods in systems biology. Preface.

PMID- 21943920
TI  - Amphiphilic hollow carbonaceous microspheres for the sorption of phenol from
      water.
AB  - Amphiphilic porous hollow carbonaceous spheres (PHCSs) were synthesized via mild
      hydrothermal treatment of yeast cells and further pyrolyzing post treatment. The
      morphology, chemical composition, porosity, and structure of the carbonaceous
      materials were investigated. It is evident that the carbonaceous materials were
      composed of the carbonized organic matter (COM) and the noncarbonized organic
      matter (NOM), and the relative COM and NOM fractions could be adjusted through
      changing the temperature of hydrothermal and/or pyrolyzing treatment. The phenol
      sorption properties of the carbonaceous materials had been investigated and the
      sorption isotherms fit well to the modified Freundlich equation. It was found
      that the sorption isotherm of phenol onto PHCSs was practically linear even at
      extreme high concentrations, which was fewer reported for activated carbon or
      other inorganic materials. This type of sorption isothermals was assigned to a
      partition mechanism, and the largest value of the partition coefficient (K(f))
      and carbon-normalized K(f) (K(oc)) is 56.7 and 91.5 mL g(-1), respectively.
      Moreover, PHCSs exhibit fast sorption kinetic and facile regeneration property.
      The results indicate PHCSs are potential effective sorbents for removal of
      undesirable organic chemicals in wastewater, especially at high concentrations.

PMID- 21943921
TI  - Partitioning of hexachlorobenzene in a kaolin/humic acid/surfactant/water system:
      combined effect of surfactant and soil organic matter.
AB  - Understanding the combined effect of soil organic matter (SOM) and surfactants on
      the partitioning of hydrophobic organic compounds in soil/water systems is
      important to predict the effectiveness of surfactant-enhanced remediation (SER).
      In the present study we investigate the partitioning of hexachlorobenzene (HCB)
      within a humic acid (HA)-coated kaolin/Triton X-100 (TX100)/water system, with
      special emphasis on the interaction between TX100 and HA, and their combined
      effect on HCB sorption. HA firstly enhanced then suppressed TX100 sorption to
      kaolin as the amounts of HA increased, while the addition of TX100 led to a
      consistent reduction in HA sorption. In the HA-coated kaolin/TX100/water system,
      TX100 played a primary role in enhancing desorption of HCB, while the role could
      be suppressed and then enhanced as HA coating amounts increased. Only at HA
      coating above 2.4%, dissolved HA outcompeted clay-bound HA for HCB partitioning,
      resulting in dissolved HA enhanced desorption. The presence of dissolved HA at
      these conditions further promoted the effectiveness of TX100 enhanced desorption.
      Despite a reduced TX100 sorption to clay was achieved due to the presence of
      dissolved HA, the effect on HCB desorption was comparatively slight. A reliable
      cumulative influence of HA and TX100 on HCB desorption was observed, although HCB
      desorption by HA/TX100 mixed was less than the sum of HA and TX100 individually.
      Our study suggests that for soils of high organic contents, the combined effect
      of SOM and surfactants on HOCs desorption can be applied to improve the
      performance of SER.

PMID- 21943922
TI  - Treatment of emerging contaminants in wastewater treatment plants (WWTP)
      effluents by solar photocatalysis using low TiO2 concentrations.
AB  - The optimal photocatalyst concentration for industrial wastewater treatment in
      current photoreactor designs is several hundreds of milligrams per liter.
      However, the elimination of emerging contaminants (ECs), which are present at
      extremely low concentrations in waste water treatment plants (WWTP) effluents
      might be accomplished at much lower catalyst (TiO(2)) concentrations. One of the
      main drawbacks of reducing catalyst loading below the optimum is the loss of
      useful photons which instead are transmitted through the TiO(2) suspension
      without being absorbed by the catalyst. Accordingly, in this work, laboratory and
      solar pilot-scale experiments were performed with real WWTP effluents to evaluate
      the kinetics of photocatalytic degradation of 52 emerging contaminants under
      realistic (ppb) concentrations. The analysis of the samples was accomplished by
      solid phase extraction (SPE) followed by liquid chromatography-mass spectrometry
      (LC-MS). In view of the results, low concentrations of TiO(2) of the order of
      tens of milligrams per liter were found to be insufficient for the degradation of
      the ECs in photoreactors with a short light-path length (29 cm). However, it was
      established that solar reactors of diameters of several hundreds of millimetres
      could be used for the efficient removal of ECs from WWTP effluents. The results
      presented show a general methodology for selecting the most efficient reactor
      diameter on the basis of the desired catalyst concentration.

PMID- 21943923
TI  - Alkaline modified oil shale fly ash: optimal synthesis conditions and preliminary
      tests on CO2 adsorption.
AB  - Environmentally friendly product, calcium-silica-aluminum hydrate, was
      synthesized from oil shale fly ash, which is rendered so far partly as an
      industrial waste. Reaction conditions were: temperature 130 and 160 degrees C,
      NaOH concentrations 1, 3, 5 and 8M and synthesis time 24h. Optimal conditions
      were found to be 5M at 130 degrees C at given parameter range. Original and
      activated ash samples were characterized by XRD, XRF, SEM, EFTEM, (29)Si MAS-NMR,
      BET and TGA. Semi-quantitative XRD and MAS-NMR showed that mainly tobermorites
      and katoite are formed during alkaline hydrothermal treatment. Physical
      adsorption of CO(2) on the surface of the original and activated ash samples was
      measured with thermo-gravimetric analysis. TGA showed that the physical
      adsorption of CO(2) on the oil shale fly ash sample increases from 0.06 to 3-4
      mass% after alkaline hydrothermal activation with NaOH. The activated product has
      a potential to be used in industrial processes for physical adsorption of CO(2)
      emissions.

PMID- 21943924
TI  - Feasibility study on the use of soil washing to remediate the As-Hg contamination
      at an ancient mining and metallurgy area.
AB  - Soils in abandoned mining sites generally present high concentrations of trace
      elements, such as As and Hg. Here we assessed the feasibility of washing
      procedures to physically separate these toxic elements from soils affected by a
      considerable amount of mining and metallurgical waste ("La Soterrana", Asturias,
      NW Spain). After exhaustive soil sampling and subsequent particle-size separation
      via wet sieving, chemical and mineralogical analysis revealed that the finer
      fractions held very high concentrations of As (up to 32,500 ppm) and Hg (up to
      1600 ppm). These elements were both associated mainly with Fe/Mn oxides and
      hydroxides. Textural and geochemical data were correlated with the geological
      substrate by means of a multivariate statistical analysis. In addition, the Hg
      liberation size (below 200 MUm) was determined to be main factor conditioning the
      selection of suitable soil washing strategies. These studies were finally
      complemented with a specific-gravity study performed with a C800 Mozley separator
      together with a grindability test, both novel approaches in soil washing
      feasibility studies. The results highlighted the difficulties in treating "La
      Soterrana" soils. These difficulties are attributed to the presence of
      contaminants embedded in the soil and spoil heap aggregates, caused by the
      meteorization of gangue and ore minerals. As a result of these two
      characteristics, high concentrations of the contaminants accumulate in all grain
      size fractions. Therefore, the soil washing approach proposed here includes the
      grinding of particles above 125 MUm.

PMID- 21943925
TI  - Nationwide survey on the epidemiology of syringomyelia in Japan.
AB  - BACKGROUND: Syringomyelia is a rare disease characterized by abnormal fluid
      filled cavities within the spinal cord, and is associated with Chiari
      malformations, arachnoiditis, or spinal cord tumors. The widespread availability
      of magnetic resonance imaging (MRI) in Japan has allowed for easy identification
      of syrinxes. The aim of this study was to survey the clinicoepidemiological
      characteristics of syringomyelia in Japan. METHODS: A 2-stage postal survey was
      conducted in late 2009. The first survey aimed to estimate the number of patients
      with syringomyelia, and the second survey aimed to elucidate
      clinicoepidemiological characteristics. Diagnosis of syringomyelia was based on
      the findings of MRI or computed tomographic myelography. RESULTS: In the first
      survey, we received 2133 responses from 2937 randomly selected departments and
      collected data of 1215 syringomyelia patients (543 men and 672 women). The total
      response rate for the first survey was 73%. The estimated prevalence of
      ambulatory syringomyelia patients in Japan was 1.94 per 100000. In the second
      survey, the proportion of asymptomatic syringomyelia patients was 22.7%. Chiari
      type I malformations and idiopathic syringomyelia were the first and second most
      common etiologies. CONCLUSIONS: Our nationwide survey indicated that widespread
      MRI availability has contributed to the diagnosis of both asymptomatic and
      idiopathic cases.

PMID- 21943926
TI  - The diagnostic power of direct carbohydrate-deficient transferrin immunoassay in
      alcoholics. Absolute or relative values?
AB  - The objective of this study was to compare the diagnostic power of direct
      carbohydrate-deficient transferrin (CDT) immunoassay in alcohol abuse expressed
      in relative units with the diagnostic power of the results expressed in absolute
      units. Serum CDT was determined in 127 alcoholics using N Latex CDT direct
      immunonephelometric assay (Siemens Healthcare Diagnostics, Marburg, Germany). The
      diagnostic sensitivity, specificity, negative and positive predictive value, and
      also the positive and negative likelihood ratios do not differ between results
      expressed in relative or absolute units independently of cutoff chosen. Finally,
      the area under the receiver operating characteristic (ROC) curves for N Latex CDT
      test expressed in absolute units does not differ from the area for results
      expressed in relative units. We conclude that the diagnostic usefulness of N
      Latex immunonephelometric assay using the relative or absolute values is the
      same.

PMID- 21943927
TI  - Low carbohydrate ketogenic diet prevents the induction of diabetes using
      streptozotocin in rats.
AB  - Diabetes continues to be an overwhelmingly prevalent endocrine disorder that
      leads to several micro- and macrocomplications. It has been widely accepted that
      changes in dietary habits could induce or prevent the onset of diabetes. It is
      shown that low carbohydrate ketogenic diet (LCKD) is effective in the
      amelioration of many of the deleterious consequences of diabetes. However, its
      role in preventing the onset of diabetes is not understood. Therefore, this study
      is focused on the effect of LCKD in preventing the induction of diabetes using
      streptozotocin (STZ) in rats by biochemical and histological methods. Forty-two
      Wistar rats weighing 150-250 g were used in this study. The animals were divided
      into three groups: normal diet (ND), low carbohydrate ketogenic diet (LCKD), and
      high carbohydrate diet (HCD). Specific diets ad libitum were given to each group
      of animals for a period of 8 weeks. Each group was further subdivided into normal
      control, sham control and diabetic groups. Animals in the diabetic group were
      given a single intraperitoneal injection of STZ (55 mg/kg). All the animals were
      sacrificed 4 weeks after the injection of STZ. Daily measurements of food and
      water intake as well as weekly measurement of body weight were taken during the
      whole 12 weeks of the experiment. After injecting with STZ, the blood glucose
      level of all the groups increased significantly except for the group fed on LCKD
      (p value<0.01). Also, food intake, water intake and urine output were
      significantly increased in all groups except for the LCKD group (p value<0.01).
      There was also a significant decrease in the weight gain of the animals that were
      fed on a LCKD as compared to other groups (p value<0.05). Although, substantial
      decrease in the number of beta cells was noticed in diabetic rats, there were no
      change in the number of beta cells in the LCKD treated diabetic animals as
      compared to LCKD control group. The results presented in this study, therefore,
      suggests that LCKD prevents the development of diabetes using streptozotocin in
      rats.

PMID- 21943928
TI  - Type D (distressed) personality is associated with poor quality of life and
      mental health among 3080 cancer survivors.
AB  - BACKGROUND: This study assessed the association between Type D personality (the
      conjoint effect of negative affectivity and social inhibition) and quality of
      life (QoL) and mental health of cancer survivors up to 10 years post-diagnosis.
      METHODS: All currently alive individuals diagnosed with endometrial or colorectal
      cancer between 1998 and 2007, or with lymphoma or multiple myeloma between 1999
      and 2008 as registered in the Eindhoven Cancer Registry received a questionnaire
      on Type D personality (DS14), QoL (SF-36 or EORTC-QLQ-C30) and mental health
      (HADS). RESULTS: Of the 3080 survivors who responded (69%), 572 (19%) had a Type
      D personality. Type D survivors had clinically meaningful lower levels of general
      health, social functioning, role-function emotional, mental health and vitality
      compared to non-Type D's (SF-36: all P's<0.001). They also reported clinically
      meaningful worse emotional and social functioning, global health status/QoL, and
      more fatigue (EORTC-QLQ-C30: all P's<0.001). This was also confirmed by
      multivariate logistic regression analyses showing that cancer survivors with a
      Type D personality were more likely to experience a decreased QoL on all SF-36
      and EORTC-QLQ-C30 scales (all ORs ranging between 1.88 and 5.56). The proportion
      of survivors reporting an impaired QoL was higher among Type D (35-64%) than non
      Type D's (20-36%). Finally, Type D's were more likely to be depressed (44% vs.
      13%; P<0.0001) or anxious (51% vs. 14%; P<0.0001). CONCLUSIONS: Cancer survivors
      with a Type D personality are at increased risk of impaired QoL and mental health
      problems that cannot be explained by socio-demographic or clinical
      characteristics.

PMID- 21943929
TI  - Two-year outcomes in first-episode psychotic depression the McLean-Harvard First
      Episode Project.
AB  - OBJECTIVE: Early assessment can guide accurate diagnosis, prognosis, and
      treatment-planning for patients with major mental illnesses. Longitudinal studies
      in psychotic depression from onset are rare, encouraging the present study.
      METHOD: We followed 56 DSM-IV MDD patients with psychotic features prospectively
      and systematically to assess course and predictors of operationally-defined
      syndromal remission, syndromal recovery, symptomatic remission, functional
      recovery, and new episodes, and to evaluate diagnostic stability. RESULTS: Among
      49/56 cases followed for >=2 years, 59% retained the initial diagnosis and most
      achieved syndromal remission (86%) and recovery (84%); 58% remitted
      symptomatically, and only 35% (17/49) recovered functionally. Syndromal recovery
      was earlier following subacute onset, lower initial depression scores, and lack
      of moodincongruent psychotic features. Within 2 years, 45% (22/49) experienced
      new episodes - earlier with younger onset and higher CGI scores. DSM diagnosis
      changed in 41%, to bipolar (33%), or schizoaffective disorders (12%), which
      followed early mania-like or schizophrenia-like features, respectively.
      CONCLUSIONS: Within 2 years of first-hospitalizations, 41% of patients initially
      diagnosed with psychotic-depression met criteria for DSM-IV bipolar or
      schizoaffective disorders. Of the 59% retaining the initial diagnosis for 2
      years, nearly half experienced new episodes, 42% remained symptomatic, and two
      thirds failed to regain their own prior functional status.

PMID- 21943930
TI  - Episode cycles with increasing recurrences in first-episode bipolar-I disorder
      patients.
AB  - BACKGROUND: Preliminary review of a century of studies of the course of manic
      depressive syndromes produced 40 reports, of which approximately one-third report
      evidence of shortening wellness intervals or cycle-lengths with more recurrences,
      and two-thirds did not. METHODS: We evaluated inter-episode intervals (cycle
      length) in 128 clinically-treated, DSM-IV bipolar-I disorder patients followed
      prospectively and systematically over 5.7 years, with 6.5 episodes/person.
      RESULTS: As expected, cycle-length varied inversely with total cycle
      count/person; however, multivariate linear regression found only longer initial
      hospitalization and fewer total cycles to be associated with cycle-length,
      whereas cycle-number (1, 2, 3, etc.), sex, intake-age, and first-episode polarity
      were not. Regression of within-subject cycle-length versus cycle-number yielded
      individual slope-functions with pseudo-random distribution (28% fell within +/-1
      month/cycle of the null [zero-slope]). Mean duration of early and late euthymic
      intervals (cycles 2 vs. 5) in patients with matched recurrence-counts was nearly
      identical. CONCLUSIONS: The course of bipolar-I disorder from onset was largely
      random or chaotic over nearly 6 years from onset. Only a minority of patients
      showed either cycle-acceleration or slowing, without changes in wellness
      intervals. The findings may be influenced by treatment-effects, but seem to
      indicate that most current bipolar-I disorder patients are unlikely to show
      progressive shortening of recurrence-cycles.

PMID- 21943931
TI  - Electrocardiographic features of sarcomere mutation carriers with and without
      clinically overt hypertrophic cardiomyopathy.
AB  - In hypertrophic cardiomyopathy (HC), electrocardiographic (ECG) changes have been
      postulated to be an early marker of disease, detectable in sarcomere mutation
      carriers when left ventricular (LV) wall thickness is still normal. However, the
      ECG features of mutation carriers have not been fully characterized. Therefore,
      we systematically analyzed ECGs in a genotyped HC population to characterize ECG
      findings in mutation carriers (G+) with and without echocardiographic LV
      hypertrophy (LVH), and to evaluate the accuracy of ECG findings to differentiate
      at-risk mutation carriers from genetically unaffected relatives during family
      screening. The ECG and echocardiographic findings were analyzed from 213
      genotyped subjects (76 G+/LVH-, 57 G+/LVH+ overt HC, 80 genetically unaffected
      controls). Cardiac magnetic resonance imaging was available on a subset. Q waves
      and repolarization abnormalities (QST) were highly specific (98% specificity)
      markers for LVH- mutation carriers, present in 25% of G+/LVH- subjects, and 3% of
      controls (p <0.001). QST ECG abnormalities remained independently predictive of
      carrying a sarcomere mutation after adjusting for age and impaired relaxation,
      another distinguishing feature of G+/LVH- subjects (odds ratio 8.4, p = 0.007).
      Myocardial scar or perfusion abnormalities were not detected on cardiac magnetic
      resonance imaging in G+/LVH- subjects, irrespective of the ECG features. In overt
      HC, 75% had Q waves and/or repolarization changes, but <25% demonstrated common
      isolated voltage criteria for LVH. In conclusion, Q waves and repolarization
      abnormalities are the most discriminating ECG features of sarcomere mutation
      carriers with and without LVH. However, owing to the limited sensitivity of ECG
      and echocardiographic screening, genetic testing is required to definitively
      identify at-risk family members.

PMID- 21943932
TI  - Impact of mitral regurgitation on exercise capacity and clinical outcomes in
      patients with ischemic left ventricular dysfunction.
AB  - There is uncertainty and debate regarding whether ischemic mitral regurgitation
      (MR) is a secondary epiphenomenon resulting from left ventricular (LV)
      dysfunction or confers an independent effect on exercise capacity and outcomes.
      We tested whether ischemic MR negatively affects exercise capacity and
      cardiovascular morbidity and mortality in patients with coronary artery disease
      (CAD) and those with inferior wall motion abnormality independent of LV
      dysfunction. Clinical follow-up over 5 years was obtained in 77 patients (64 +/-
      10 years old, LV ejection fraction 54 +/- 11%) with at least mild ischemic MR
      from CAD and evidence of inferior wall motion abnormality who had exercise stress
      testing with perfusion imaging within 24 hours of echocardiography. Patients with
      active heart failure, ischemia, intrinsic valve disease, pulmonary and vascular
      diseases were excluded. Exercise capacity (METs, peak double product) was tested
      for relation to MR (vena contracta [VC] and jet area), LV size and function, and
      pulmonary pressures. Cox proportional hazards analysis assessed whether MR
      predicted cardiovascular events including hospitalization for heart failure,
      acute coronary syndrome, and myocardial infarction and cardiovascular and total
      mortalities. Univariate correlation identified MR with VC (r = -0.674, p <0.0001)
      and MR jet area (r = -0.575, p <0.0001) as determinants of decreased functional
      capacity evaluated by METs, with VC the stronger predictor. MR VC >2 mm (moderate
      ischemic MR) and age were independent predictors of cardiovascular events and
      death (hazard ratio 6.72 for MR, p = 0.04). In conclusion, in patients with CAD
      and LV inferior wall motion abnormality, MR negatively affects exercise capacity
      and is associated with increased cardiovascular morbidity and mortality. This
      effect appears independent of degree of LV dysfunction.

PMID- 21943933
TI  - Efficacy and safety of bosentan for pulmonary arterial hypertension in adults
      with congenital heart disease.
AB  - The dual endothelin receptor antagonist, bosentan, has been shown to be well
      tolerated and effective in improving pulmonary arterial hypertension (PAH)
      symptoms in patients with Eisenmenger syndrome but data from longer-term studies
      are lacking. The aim of this study was to retrospectively analyze the long-term
      efficacy and safety of bosentan in adults with PAH secondary to congenital heart
      disease (PAH-CHD). Prospectively collected data from adult patients with PAH-CHD
      (with and without Down syndrome) initiated on bosentan from October 2007 through
      June 2010 were analyzed. Parameters measured before bosentan initiation (62.5 mg
      2 times/day for 4 weeks titrated to 125 mg 2 times/day) and at each follow-up (1
      month and 3, 6, 9, 12, 18, and 24 months) included exercise capacity (6-minute
      walk distance [6MWD]), pretest oxygen saturation, liver enzymes, and hemoglobin.
      Data were analyzed from 39 patients with PAH-CHD (10 with Down syndrome) who had
      received >= 1 dose of bosentan (mean duration of therapy 2.1 +/- 1.5 years). A
      significant (p < 0.0001) average improvement in 6MWD of 54 m over a 2-year period
      in patients with PAH-CHD without Down syndrome was observed. Men patients had a
      6MWD of 33 m greater than women (p < 0.01). In all patients, oxygen saturation,
      liver enzymes, and hemoglobin levels remained stable. There were no
      discontinuations from bosentan owing to adverse events. In conclusion, patients
      with PAH-CHD without Down syndrome gain long-term symptomatic benefits in
      exercise capacity after bosentan treatment. Men seem to benefit more on bosentan
      treatment. Bosentan appears to be well tolerated in patients with PAH-CHD with or
      without Down syndrome.

PMID- 21943935
TI  - High-performance liquid chromatographic method with amperometric detection
      employing boron-doped diamond electrode for the determination of sildenafil,
      vardenafil and their main metabolites in plasma.
AB  - A simple, fast and sensitive HPLC method with electrochemical detection employing
      boron-doped diamond electrode (BDD) for the determination of sildenafil
      (ViagraTM), vardenafil (LevitraTM) and their main metabolites, N-desmethyl
      sildenafil and N-desethyl vardenafil in human plasma is presented. The assay
      involved drug extraction by tert-butyl methyl ether and isocratic reversed-phase
      liquid chromatography with amperometric detection. Complete separation of all
      analytes was achieved within 12 min. The mobile phase consisted of 20mM sodium
      dihydrogen phosphate with 40 mM sodium perchlorate/acetonitrile (70:30, v/v), pH
      3.5. The electrode working potential was +1520 mV (vs. Pd/H(2)). Calibration
      curves were linear over the concentration range of 10-400 ng mL(-1). Phloretin
      was used as an internal standard. The limits of detection (LOD) and
      quantification (LOQ) for the studied analytes were within the range of 2-4 ng mL(
      1) and 7.0-13.4 ng mL(-1), respectively. The developed method was applied to
      human plasma samples spiked with analytes at therapeutic concentrations. The
      study confirms the method's suitability for both pharmacokinetic studies and
      therapeutic monitoring.

PMID- 21943934
TI  - Innate immune mediator profiles and their regulation in a novel polarized
      immortalized epithelial cell model derived from human endocervix.
AB  - The endocervix in the female reproductive tract (FRT) is susceptible to sexually
      transmitted pathogens such as Chlamydia trachomatis and Neisseria gonorrhoeae.
      Endocervical epithelial cells in vivo make innate immune mediators that likely
      aid in the protection from these pathogens. In vitro studies to investigate the
      innate epithelial cell immune response to endocervical pathogens have been
      hindered by the paucity of human endocervix-derived epithelial cell lines that
      display the differentiation proteins and functional characteristics of their site
      of origin. We have established an immortalized epithelial cell line (A2EN)
      derived from an endocervical tissue explant that can be polarized to exhibit
      distinct apical and basolateral membrane domains. Polarized A2EN cells secrete
      mucus at their apical surface, and express MUC5B, a mucin specific to the
      endocervix. Polarized A2EN cells also express hormone receptors that respond
      appropriately to female steroid hormones. Polarized A2EN cells can be stimulated
      with the toll-like receptor 3 agonist, polyI:C, to express anti-microbial
      peptides (AMPs) as well as pro-inflammatory cytokines and chemokines. Cytokines
      and chemokines are also differentially secreted depending on the hormone milieu
      in which the cells are exposed. We conclude that polarized A2EN cells maintain
      distinctive phenotypic and functional characteristics of the epithelial cells
      found in the endocervix and, hence, could provide a useful, new in vitro model
      system for investigations on the role of endogenous and exogenous factors that
      regulate endocervical epithelial cell immunity including studies on sexually
      transmitted infections and topical microbicides.

PMID- 21943936
TI  - A propensity-matched study of the association of diabetes mellitus with incident
      heart failure and mortality among community-dwelling older adults.
AB  - Diabetes mellitus (DM) is a risk factor for incident heart failure (HF) in older
      adults. However, the extent to which this association is independent of other
      risk factors remains unclear. Of 5,464 community-dwelling adults >=65 years old
      in the Cardiovascular Health Study without baseline HF, 862 had DM (fasting
      plasma glucose levels >=126 mg/dl or treatment with insulin or oral hypoglycemic
      agents). Propensity scores for DM were estimated for each of the 5,464
      participants and were used to assemble a cohort of 717 pairs of participants with
      and without DM who were balanced in 65 baseline characteristics. Incident HF
      occurred in 31% and 26% of matched participants with and without DM,
      respectively, during >13 years of follow-up (hazard ratio 1.45 for DM vs no DM,
      95% confidence interval [CI] 1.14 to 1.86, p = 0.003). Of the 5,464 participants
      before matching unadjusted and multivariable-adjusted hazard ratios for incident
      HF associated with DM were 2.22 (95% CI 1.94 to 2.55, p <0.001) and 1.52 (95% CI
      1.30 to 1.78, p <0.001), respectively. All-cause mortality occurred in 57% and
      47% of matched participants with and without DM, respectively (hazard ratio 1.35,
      95% CI 1.13 to 1.61, p = 0.001). Of matched participants DM-associated hazard
      ratios for incident peripheral arterial disease, incident acute myocardial
      infarction, and incident stroke were 2.50 (95% CI 1.45 to 4.32, p = 0.001), 1.37
      (95% CI 0.97 to 1.93, p = 0.072), and 1.11 (95% CI 0.81 to 1.51, p = 0.527),
      respectively. In conclusion, the association of DM with incident HF and all-cause
      mortality in community-dwelling older adults without HF is independent of major
      baseline cardiovascular risk factors.

PMID- 21943937
TI  - Deactivation of implantable cardioverter defibrillators in terminal illness and
      end of life care.
AB  - Cardiology professional societies have recommended that patients with
      cardiovascular implantable electronic devices complete advance directives (ADs).
      However, physicians rarely discuss end of life handling of implantable
      cardioverter defibrillators (ICDs), and standard AD forms do not address the
      presence of ICDs. We conducted a telephone survey of 278 patients with an ICD
      from a large, academic hospital. The average period since implantation was 5.15
      years. More than 1/3 (38%) had been shocked, with a mean of 4.69 shocks. More
      than 1/2 had executed an AD, but only 3 had included a plan for their ICD. Most
      subjects (86%) had never considered what to do with their ICD if they had a
      serious illness and were unlikely to survive. When asked about ICD deactivation
      in an end of life situation, 42% said it would depend, 28% favored deactivation,
      and 11% would not deactivate. One quarter (26%) thought ICD deactivation was a
      form of assisted suicide, 22% thought a do not resuscitate order did not mean
      that the ICD should be deactivated, and 46% responded that the ICD should not be
      automatically deactivated in hospice. The answers did not correlate with any
      demographic factors. Almost all (95%) agreed that patients should have the
      opportunity to execute an AD that directs handing of an ICD. When asked who
      should be responsible for discussing this device for an AD, 31% said
      electrophysiologists, 45% said general cardiologists, and 14% said primary care
      physicians. In conclusion, the results of the present study highlight the lack of
      consensus among patients with an ICD on the issue of deactivation at the end of a
      patient's life. These findings suggest cardiologists should discuss end of life
      care and device deactivation with their patients with an ICD.

PMID- 21943939
TI  - Arrhythmic manifestations in patients with congenital left ventricular aneurysms
      and diverticula.
AB  - Congenital left ventricular aneurysms and diverticula (LVA/Ds) are rare cardiac
      malformations that can be detected using echocardiography or other imaging
      techniques. Some of these patients present with ventricular arrhythmias. This
      study investigated clinical characteristics of patients with congenital LVA/D
      presenting with arrhythmic manifestations. Over the previous 20 years 250
      patients were diagnosed to have congenital LVA/D at our institution. Diagnosis
      was made using echocardiography after exclusion of coronary artery disease, local
      cardiac inflammatory processes, traumatic causes, or cardiomyopathies. At initial
      presentation 32 of the 250 patients (13%, average age 45 years, range 25 to 65,
      21 men and 11 women) exhibited arrhythmias. At least 2 LVA/Ds were present in 6
      of these patients. LVA/Ds were localized at the posterobasal, apical,
      anteroseptal, and anterolateral walls in 12, 11, 4, and 5 patients, respectively.
      The most common complaints at presentation were syncope or presyncope in 18
      patients and palpitations in 11 patients. One patient had survived sudden cardiac
      death. Long-term electrocardiographic recordings showed ventricular tachycardia
      (VT) or ventricular fibrillation in 17 patients (53%). Twelve patients underwent
      electrophysiologic testing. Nine patients had inducible ventricular
      tachyarrhythmia, whereas induced tachycardia was similar to that during
      spontaneous arrhythmia in 7 patients. In conclusion, patients with congenital
      LVA/Ds who present with arrhythmic manifestations commonly have VT.
      Electrophysiologic testing can reproduce clinical VT in most of these patients.

PMID- 21943938
TI  - Usefulness of stress gated technetium-99m single photon emission computed
      tomographic myocardial perfusion imaging for the prediction of cardiac death in
      patients with moderate to severe left ventricular systolic dysfunction and
      suspected coronary artery disease.
AB  - Although stress gated technetium-99m single-photon emission computed tomographic
      (SPECT) myocardial perfusion imaging (MPI) is useful in differentiating ischemic
      from nonischemic cardiomyopathy, its prognostic usefulness in this patient
      population is not well understood. Consecutive unique patients with suspected
      coronary artery disease who, for clinical indications, underwent technetium-99m
      rest and stress MPI demonstrating ejection fractions <=40% by gated SPECT imaging
      were retrospectively identified. In addition to prescan variables, previously
      defined cutoffs for gated SPECT parameters using visual and standard 17-segment
      semiquantitative scoring were applied and related to the occurrence of cardiac
      death up to 5 years after MPI. Of the 475 patients fulfilling criteria for study
      inclusion, follow-up was complete in 444 (93%) over 3.7 +/- 1.6 years. Of 393
      patients without subsequent early (<=60 days) coronary revascularization, cardiac
      death occurred in 64 (16%). The summed stress score, an MPI measure of the extent
      and severity of coronary artery disease that also accounts for the ischemic
      burden, was the gated SPECT parameter most related to cardiac death with Kaplan
      Meier 5-year cardiac death-free survival of 85.6% and 67.3% in patients with
      summed stress scores <=8 and >8, respectively (p <0.001). In multivariate Cox
      regression analysis, a summed stress score >8 independently contributed to
      cardiac death (adjusted hazard ratio 2.20, 95% confidence interval 1.34 to 3.61),
      and its addition to the model significantly increased the global chi-square value
      over prescan variables (from 32.46 to 41.67, p = 0.002). In conclusion, stress
      MPI data from gated technetium-99m SPECT scans are useful for the prediction of
      cardiac death in patients with moderate to severe left ventricular systolic
      dysfunction in whom there is suspicion of underlying coronary artery disease.

PMID- 21943940
TI  - Impact of iso-osmolar versus low-osmolar contrast agents on contrast-induced
      nephropathy and tissue reperfusion in unselected patients with ST-segment
      elevation myocardial infarction undergoing primary percutaneous coronary
      intervention (from the Contrast Media and Nephrotoxicity Following Primary
      Angioplasty for Acute Myocardial Infarction [CONTRAST-AMI] Trial).
AB  - Conflicting data have been reported on the effects of low-osmolar and iso-osmolar
      contrast media on contrast-induced acute kidney injury (CI-AKI). In particular,
      no clinical trial has yet focused on the effect of contemporary contrast media on
      CI-AKI, epicardial flow, and microcirculatory function in patients with ST
      segment elevation acute myocardial infarction who undergo primary percutaneous
      coronary intervention. The Contrast Media and Nephrotoxicity Following Coronary
      Revascularization by Angioplasty for Acute Myocardial Infarction (CONTRAST-AMI)
      trial is a prospective, randomized, single-blind, parallel-group, noninferiority
      study aiming to evaluate the effects of the low-osmolar contrast medium iopromide
      compared to the iso-osmolar agent iodixanol on CI-AKI and tissue-level perfusion
      in patients with ST-segment elevation acute myocardial infarction. Four hundred
      seventy-five consecutive, unselected patients who underwent primary percutaneous
      coronary intervention were randomized to iopromide (n = 239) or iodixanol (n =
      236). All patients received high-dose N-acetylcysteine and hydration. The primary
      end point was the proportion of patients with serum creatinine (sCr) increases
      >=25% from baseline to 72 hours. Secondary end points were Thrombolysis In
      Myocardial Infarction (TIMI) myocardial perfusion grade, increase in sCr >=50%,
      increase in sCr >=0.5 or >=1 mg/dl, and 1-month major adverse cardiac events. The
      primary end point occurred in 10% of the iopromide group and in 13% of the
      iodixanol group (95% confidence interval -9% to 3%, p for noninferiority =
      0.0002). A TIMI myocardial perfusion grade of 0 or 1 was present in 14% of
      patients in the 2 groups. No differences between the 2 groups were found in any
      of the secondary analyses of sCr increase. No significant difference in 1-month
      major adverse cardiac events was found (8% vs 6%, p = 0.37). In conclusion, in a
      population of unselected patients with ST-segment elevation acute myocardial
      infarction who underwent primary percutaneous coronary intervention, iopromide
      was not inferior to iodixanol in the occurrence of CI-AKI; no significant
      differences were found in terms of tissue-level reperfusion and major adverse
      cardiac events between the 2 contrast agents.

PMID- 21943941
TI  - Is it time to revise the asthma guidelines?

PMID- 21943942
TI  - Chemical toxicity to keratinocytes triggers dendritic cell activation via an IL
      1alpha path.

PMID- 21943943
TI  - Beryllium-specific CD4+ T cells in blood as a biomarker of disease progression.
AB  - BACKGROUND: CD4(+) T cells are responsible for the progressive lung damage seen
      in patients with chronic beryllium disease (CBD), a granulomatous lung disorder
      in which antigen-specific, T(H)1-type, cytokine-secreting T cells have been
      characterized. Compared with those seen in beryllium (Be)-sensitized subjects,
      increased numbers of Be-responsive T cells are present in the blood of patients
      with CBD. OBJECTIVE: The aim of this study was to determine whether the number of
      Be-specific T cells in blood predicted the development of CBD in a cohort of Be
      exposed subjects. METHODS: Using IFN-gamma ELISpot and proliferation-based
      assays, we determined the frequency and proliferative capacity of Be-responsive T
      cells in blood. RESULTS: Compared with the Be lymphocyte proliferation test,
      which detected an abnormal Be-induced proliferative response in 11 (4.2%) of 260
      workers from a Be-machining facility, the IFN-gamma ELISpot detected a
      sensitization rate of 10% (chi(2) = 55.7, P < .0001). A significant positive
      correlation was also noted between the number of Be-responsive CD4(+) T cells in
      the blood and lung tissue of patients with CBD. Importantly, the transition from
      Be sensitization to CBD was associated with an increased number of antigen
      specific T cells in blood. CONCLUSION: These findings have important implications
      for Be-induced disease and potentially other immune-mediated disorders,
      suggesting that the frequency of antigen-specific T cells in blood can serve as a
      noninvasive biomarker to predict disease development and severity of the Be
      specific CD4(+) T-cell alveolitis.

PMID- 21943945
TI  - High resolution intra-operative two-dimensional specimen mammography and its
      impact on second operation for re-excision of positive margins at final pathology
      after breast conservation surgery.
AB  - BACKGROUND: In the United States, about 50% to 66% of women undergoing breast
      conservation surgery for cancer undergo subsequent mastectomy for positive
      margins on initial lumpectomy. This is despite the fact that screening
      mammography has resulted in a decrease in the size of newly diagnosed breast
      cancer to <2 cm. METHODS: A retrospective review of 128 patients who underwent
      breast conservation surgery for early breast cancer was performed using
      intraoperative 2-dimensional Faxitron high-resolution specimen mammography
      without specimen compression as the only margin assessment technique. Of these,
      29 patients had histories of lumpectomy with positive margins. RESULTS: A total
      of 131 procedures were performed. Margins were histologically clear at initial
      breast conservation surgery in 84.3% of patients who underwent primary
      lumpectomy. Subsequent reexcision for positive margins was required in 14.7% of
      patients. Two-dimensional Faxitron mammographically guided intraoperative
      reexcision cleared the margins in 95.8% of patients (23 of 24) who would have
      otherwise required subsequent reexcision. CONCLUSIONS: Intraoperative 2
      dimensional Faxitron high-resolution specimen mammography can decrease rates of
      margin positivity and has the potential to diminish the number of subsequent
      undesired mastectomies for positive margins.

PMID- 21943944
TI  - Increased expression of CC chemokine ligand 18 in patients with chronic
      rhinosinusitis with nasal polyps.
AB  - BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with
      T(H)2-dominant inflammation, including eosinophilia, which is in contrast to
      chronic rhinosinusitis (CRS) without nasal polyps (NPs). CC chemokine ligand 18
      (CCL18)/pulmonary and activation-regulated chemokine is known to recruit naive T
      cells, B cells, and immature dendritic cells, as well as to activate fibroblasts.
      CCL18 is thought to be involved in T(H)2-related inflammatory diseases, including
      asthma and atopic dermatitis. OBJECTIVE: The objective of this study was to
      investigate the expression of CCL18 in patients with CRS. METHODS: Using NP
      tissue and uncinate tissue (UT) from control subjects and patients with CRS, we
      examined the expression of CCL18 mRNA using real-time PCR and measured CCL18
      protein using ELISA, Western blotting, and immunofluorescence. RESULTS: Compared
      with UT tissue from control subjects, CCL18 mRNA levels were significantly
      increased in NPs (P < .001) and UT (P < .05) from patients with CRSwNP but not in
      UT from patients with CRS without NPs. Similarly, CCL18 protein levels were
      increased in NPs and UT from patients with CRSwNP, and levels were even higher in
      patients with Samter's triad. Immunohistochemical analysis revealed CCL18
      expression in inflammatory cells, and CCL18(+) cell numbers were significantly
      increased in NPs. Immunofluorescence data showed colocalization of CCL18 in
      CD68(+)/CD163(+)/macrophage mannose receptor-positive M2 macrophages and tryptase
      positive mast cells in NPs. Levels of CCL18 correlated with markers of M2
      macrophages but not with tryptase levels, suggesting that M2 macrophages are
      major CCL18-producing cells in NPs. CONCLUSION: Overproduction of CCL18 might
      contribute to the pathogenesis of CRSwNP through its known activities, which
      include recruitment of lymphocytes and dendritic cells, activation of
      fibroblasts, and initiation of local inflammation.

PMID- 21943946
TI  - Hypotension is 100 mm Hg on the battlefield.
AB  - BACKGROUND: Historically, emergency physicians and trauma surgeons have referred
      to a systolic blood pressure (SBP) of 90 mm Hg as hypotension. Recent evidence
      from the civilian trauma literature suggests that 110 mm Hg may be more
      appropriate based on associated acidosis and outcome measures. In this analysis,
      we sought to determine the relationship between SBP, hypoperfusion, and mortality
      in the combat casualty. METHODS: A total of 7,180 US military combat casualties
      from the Joint Theater Trauma Registry from 2002 to 2009 were analyzed with
      respect to admission SBP, base deficit, and mortality. Base deficit, as a measure
      of hypoperfusion, and mortality were plotted against 10-mm Hg increments in
      admission SBP. RESULTS: By plotting SBP, baseline mortality was less than 2% down
      to a level of 101 to 110 mm Hg, at which point the slope of the curve increased
      dramatically to a mortality rate of 45.1% in casualties with an SBP of 60 mm Hg
      or less but more than 0 mm Hg. A presenting SBP of 0 mm Hg was associated with
      100% mortality. The data also established a similar effect for base deficit with
      a sharp increase in the rate of acidosis, which became manifest at an SBP in the
      range of 90 to 100 mm Hg. CONCLUSIONS: This analysis shows that an SBP of 100 mm
      Hg or less may be a better and more clinically relevant definition of hypotension
      and impending hypoperfusion in the combat casualty. One utility of this analysis
      may be the more expeditious identification of battlefield casualties in need of
      life-saving interventions such as the need for blood or surgical intervention.

PMID- 21943947
TI  - Should we, not could we? A commentary on "Pyloric valve transposition as
      substitute for a colostomy in humans: a preliminary report".

PMID- 21943948
TI  - Peritoneal computed tomography attenuation values reflect the severity of
      peritonitis caused by gastrointestinal perforations.
AB  - BACKGROUND: The aim of this study was to evaluate the peritoneal computed
      tomography (CT) attenuation values and relate them to the severity of peritonitis
      in patients with gastrointestinal tract (GI) perforations. METHODS: A total of 56
      consecutive patients with GI perforations who underwent CT scan and emergency
      laparotomy in our hospital were enrolled in this study. The CT attenuation values
      of the peritoneum were measured on a workstation by 2 independent investigators,
      and were investigated in relation to the severity of illness and hospital
      mortality. RESULTS: Peritoneal CT attenuation values in hospital nonsurvivors
      were significantly lower than those in survivors. There was significant negative
      correlation between peritoneal CT attenuation values and sequential organ failure
      assessment score, acute physiology and chronic health evaluation II score, and
      the Mannheim peritonitis index. CONCLUSIONS: The evaluation of peritoneal CT
      attenuation values in patients with peritonitis is simple and can be used for
      objective assessment of the severity of peritonitis.

PMID- 21943949
TI  - Profiling adult intussusception patients: comparing colonic versus enteric
      intussusception.
AB  - BACKGROUND: Adult intussusception is a rare entity representing 1% of all adult
      bowel obstruction, hospital admissions secondary to intussusception historically
      has ranged between .003% and .02%. There is limited knowledge regarding enteric
      and colonic surgical intussusception patients and their associated conditions.
      METHODS: A retrospective study was conducted using data from the National
      Inpatient Sample from 1998 to 2006. The inclusion criteria were surgical patients
      with intussusception. RESULTS: A total of 1,178 cases of intussusception
      requiring surgery were isolated from the database. The mean patient age was 49.57
      years, about 58% were females, 99.43% of this population was insured, and the
      overall mortality rate was 1.70%. Colonic resection was associated with greater
      mortality compared with the enteric resection group (P = .018). CONCLUSIONS: This
      was a large study on surgical adult intussusception patients conducted in the
      United States. We show differences in demography, comorbidities, and potential
      causes between colonic and enteric intussusception.

PMID- 21943950
TI  - Self vs expert assessment of technical and non-technical skills in high fidelity
      simulation.
AB  - BACKGROUND: Accurate assessment is imperative for learning, feedback and
      progression. The aim of this study was to examine whether surgeons can accurately
      self-assess their technical and nontechnical skills compared with expert faculty
      members' assessments. METHODS: Twenty-five surgeons performed a laparoscopic
      cholecystectomy (LC) in a simulated operating room. Technical and nontechnical
      performance was assessed by participants and faculty members using the validated
      Objective Structured Assessment of Technical Skills (OSATS) and the Non-Technical
      Skills for Surgeons scale (NOTSS). RESULTS: Assessment of technical performance
      correlated between self and faculty members' ratings for experienced (median
      score, 30.0 vs 31.0; rho = .831; P = .001) and inexperienced (median score, 22.0
      vs 28.0; rho = .761; P = .003) surgeons. Assessment of nontechnical skills
      between self and faculty members did not correlate for experienced surgeons
      (median score, 8.0 vs 10.5; rho = -.375; P = .229) or their more inexperienced
      counterparts (median score, 9.0 vs 7.0; rho = -.018; P = .953). CONCLUSIONS:
      Surgeons can accurately self-assess their technical skills in virtual reality LC.
      Conversely, formal assessment with faculty members' input is required for
      nontechnical skills, for which surgeons lack insight into their behaviours.

PMID- 21943951
TI  - Migration of vessel clip into the common bile duct and late formation of
      choledocholithiasis after laparoscopic cholecystectomy.
AB  - Since the first silk suture material acting as a nidus for the development of
      subsequent common bile duct stones after cholecystectomy was described in 1897,
      several investigators have reported that suture materials may cause
      choledocholithiasis. Silk, chromic catgut, parasites, and other foreign bodies
      are known occasionally to form such niduses in the common bile duct. Surgical
      hemostatic clips have been used widely and generally are considered very safe.
      The first case of postcholecystectomy clip migration was reported in 1979. Its
      exact pathogenesis remains unknown; it generally is agreed that bile duct
      injuries, inappropriate clip placements, subclinical bile leak, and infections
      also have been postulated to contribute to clip migration. We report an unusual
      case in which the core of a biliary calculus in the common bile duct was found to
      contain a surgical clip. This case illustrates the potentially abrupt and late
      development of clip-related gallstones and highlights the need for long-term
      follow-up evaluation.

PMID- 21943952
TI  - Improvement and characterization of the adhesion of electrospun PLDLA nanofibers
      on PLDLA-based 3D object substrates for orthopedic application.
AB  - Intensive research has demonstrated the clear biological potential of electrospun
      nanofibers for tissue regeneration and repair. However, nanofibers alone have
      limited mechanical properties. In this study we took poly(L-lactide-co-D-lactide)
      (PLDLA)-based 3D objects, one existing medical device (interference screws) and
      one medical device model (discs) as examples to form composites through coating
      their surface with electrospun PLDLA nanofibers. We specifically investigated the
      effects of electrospinning parameters on the improvement of adhesion of the
      electrospun nanofibers to the PLDLA-based substrates. To reveal the adhesion
      mechanisms, a novel peel test protocol was developed for the characterization of
      the adhesion and delamination phenomenon of the nanofibers deposited to
      substrates. The effect of incubation of the composites under physiological
      conditions on the adhesion of the nanofibers has also been studied. It was
      revealed that reduction of the working distance to 10 cm resulted in deposition
      of residual solvent during electrospinning of nanofibers onto the substrate,
      causing fiber-fiber bonding. Delamination of this coating occurred between the
      whole nanofiber layer and substrate, at low stress. Fibers deposited at 15 cm
      working distance were of smaller diameter and no residual solvent was observed
      during deposition. Delamination occurred between nanofiber layers, which peeled
      off under greater stress. This study represents a novel method for the alteration
      of nanofiber adhesion to substrates, and quantification of the change in the
      adhesion state, which has potential applications to develop better medical
      devices for orthopedic tissue repair and regeneration. 

PMID- 21943953
TI  - Effects of intra-uterine and early extra-uterine malnutrition on seizure
      threshold and hippocampal morphometry of pup rats.
AB  - We evaluate the influence of different malnutrition paradigms (intra-uterine x
      extra-uterine) in body and brain weight, in seizure threshold and in hippocampus
      morphometry, in developing rats. Intra-uterine malnutrition model consisted in
      reduction by half of the ration offered to pregnant  female; extrauterine
      malnutrition consisted of progressive limitation of lactation, from P2 to P15.
      Seizure induction was accomplished by exposure to flurothyl, at P15. At the same
      day animals were sacrificed. Morphometric analysis was based on hippocampal
      pyramidal and granular cells estimate  number, through volume calculation and
      cellular density. Extra-uterine malnutrition significantly reduced pups body and
      brain weight, seizure threshold and neuronal number in CA4 region only. Intra
      uterine malnutrition reduced neuronal number in CA2, CA4 and DG regions regarding
      well-nourished  and extra-uterine malnourished animals. In CA3, CA4 and dentate
      gyrus, a significant cell increase was observed in groups exposed to seizures,
      regarding similar control groups.

PMID- 21943954
TI  - School foodservice personnel's struggle with using labels to identify whole-grain
      foods.
AB  - OBJECTIVE: To describe how school foodservice personnel use current labeling
      methods to identify whole-grain products and the influence on purchasing for
      school meals. METHODS: Focus groups explored labeling methods to identify whole
      grain products and barriers to incorporating whole-grain foods in school meals.
      Qualitative analysis procedures and the constant comparative method were used to
      analyze data. RESULTS: Participants were school foodservice personnel (n = 67) in
      5 states across the United States. Limited ability and confidence were
      demonstrated in identifying whole-grain products from label information,
      statements, and claims. Participants indicated a need for a uniform labeling
      method such as whole-grain content to assist in ordering and purchasing. High
      cost and low acceptability were listed as barriers to incorporating whole-grain
      foods in school meals. CONCLUSIONS AND IMPLICATIONS: Whole-grain product labeling
      should be improved to enhance understanding by foodservice personnel so that
      whole grains are included in school meals.

PMID- 21943955
TI  - New mutations in MAPT gene causing frontotemporal lobar degeneration: biochemical
      and structural characterization.
AB  - Frontotemporal lobar degeneration (FTLD) can be sporadic or familial. The genes
      encoding the microtubule-associated protein tau (MAPT) and progranulin (GRN) are
      the most relevant genes so far known causing the hereditary forms. Following
      genetic screening of patients affected by FTLD, we identified 2 new MAPT
      mutations, P364S and G366R, the former in a sporadic case. In the study we report
      the clinical and genetic features of the patients carrying these mutations, and
      the functional effects of the mutations, analyzed in vitro in order to
      investigate their pathogenic character. Both mutations resulted in reduced
      ability of tau to promote microtubule polymerization; the P364S protein variant
      also showed a high propensity to aggregate into filaments. These results suggest
      a high probability that these mutations are pathogenic. Our findings highlight
      the importance of genetic analysis also in sporadic forms of FTLD, and the role
      of in vitro studies to evaluate the pathologic features of new mutations.

PMID- 21943957
TI  - Food allergy: mechanisms and therapeutics.
AB  - The immunologic mechanisms responsible for the development of allergic
      sensitization rather than tolerance to foods are not well understood, although
      there have been a number of recent advances in our understanding of why some
      foods are inherently allergenic. In addition, the involvement of alternative
      routes of exposure that are not inherently tolerogenic may play a role in
      sensitization to foods. Although there are no currently accepted therapeutic
      approaches to food allergy, there are a number of approaches to treatment in
      preclinical or clinical trials. Here, we review selected findings published since
      2009 that advance our understanding of mechanisms and new therapeutics for IgE
      mediated food allergy.

PMID- 21943956
TI  - No improvement after chronic ibuprofen treatment in the 5XFAD mouse model of
      Alzheimer's disease.
AB  - Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that has been reported
      to reduce the risk of developing Alzheimer's disease (AD). Its preventive effects
      in AD are likely pleiotropic as ibuprofen displays both anti-inflammatory
      activity by inhibition of cyclooxygenases and anti-amyloidogenic activity by
      modulation of gamma-secretase. In order to study the anti-inflammatory properties
      of ibuprofen independent of its anti-amyloidogenic activity, we performed a long
      term treatment study with ibuprofen in 5XFAD mice expressing a presenilin-1
      mutation that renders this AD model resistant to gamma-secretase modulation. As
      expected, ibuprofen treatment for 3 months resulted in a reduction of the
      inflammatory reaction in the 5XFAD mouse model. Importantly, an unchanged amyloid
      beta (Abeta) plaque load, an increase in soluble Abeta42 levels, and an
      aggravation of some behavioral parameters were noted, raising the question
      whether suppression of inflammation by nonsteroidal anti-inflammatory drug is
      beneficial in AD.

PMID- 21943958
TI  - FUS and TDP43 genetic variability in FTD and CBS.
AB  - This study aimed to evaluate genetic variability in the FUS and TDP-43 genes,
      known to be mainly associated with amyotrophic lateral sclerosis (ALS), in
      patients with the diagnoses of frontotemporal lobar degeneration (FTLD) and
      corticobasal syndrome (CBS). We screened the DNA of 228 patients for all the
      exons and flanking introns of FUS and TDP-43 genes. We identified 2 novel
      heterozygous missense mutations in FUS: P106L (g.22508384C>T) in a patient with
      behavioral variant frontotemporal dementia (bvFTD) and Q179H in several members
      of a family with behavioral variant FTD. We also identified the N267S mutation in
      TDP-43 in a CBS patient, previously only reported in 1 ALS family and 1 FTD
      patient. Additionally, we identified 2 previously reported heterozygous insertion
      and deletion mutations in Exon 5 of FUS; Gly174-Gly175 del GG (g. 4180-4185
      delGAGGTG) in an FTD patient and Gly175-Gly176 ins GG (g. 4185-4186 insGAGGTG) in
      a patient with diagnosis of CBS. Not least, we have found a series of variants in
      FUS also in neurologically normal controls. In summary, we report that genetic
      variability in FUS and TDP-43 encompasses a wide range of phenotypes (including
      ALS, FTD, and CBS) and that there is substantial genetic variability in FUS gene
      in neurologically normal controls.

PMID- 21943960
TI  - Clozapine induction of ERK1/2 cell signalling via the EGF receptor in mouse
      prefrontal cortex and striatum is distinct from other antipsychotic drugs.
AB  - Treatment resistance remains a major obstacle in schizophrenia, with
      antipsychotic drugs (APDs) being ineffective in about one third of cases. Poor
      response to standard therapy leaves the APD clozapine as the only effective
      treatment for many patients. The reason for the superior efficacy of clozapine is
      unknown, but as we have proposed previously it may involve modulation of
      neuroplasticity and connectivity through induction of interconnected mitogenic
      signalling pathways. These include the mitogen-activated protein kinase
      extracellular signal regulated kinase (MAPK-ERK) cascade and epidermal growth
      factor (EGF)/ErbB systems. Clozapine, distinct from other APDs, induced initial
      inhibition and subsequent activation of the ERK response in prefrontal cortical
      (PFC) neurons in vitro and in vivo, an action mediated by the EGF receptor
      (ErbB1). Here we examine additionally the striatum of C57Bl/6 mice to determine
      if clozapine, olanzapine, and haloperidol differentially regulate the ERK1/2
      pathway in a region or time-specific manner conditional on the EGF receptor.
      Following acute treatment, only clozapine caused delayed striatal ERK
      phosphorylation through EGF receptor phosphorylation (tyrosine 1068 site) and MEK
      that paralleled cortical ERK phosphorylation. Olanzapine induced initial pERK1
      specific blockade and an elevation 24-h later in PFC but had no effect in the
      striatum. By contrast, haloperidol significantly stimulated pERK1 in striatum for
      up to 8 h, but exerted limited effect in PFC. Clozapine but not olanzapine or
      haloperidol recruited the EGF receptor to signal to ERK. These in-vivo data
      reinforce our previous findings that clozapine's action may be uniquely linked to
      the EGF signalling system, potentially contributing to its distinctive clinical
      profile.

PMID- 21943959
TI  - White matter lesions and brain gray matter volume in cognitively normal elders.
AB  - Cerebral white matter lesions (WMLs) reflect small vessel disease, are common in
      elderly individuals, and are associated with cognitive impairment. We sought to
      determine the relationships between WMLs, age, gray matter (GM) volume, and
      cognition in the Cardiovascular Health Study (CHS). From the Cardiovascular
      Health Study we selected 740 cognitively normal controls with a 1.5 T magnetic
      resonance imaging (MRI) scan of the brain and a detailed diagnostic evaluation.
      WML severity was determined using a standardized visual rating system. GM volumes
      were analyzed using voxel-based morphometry implemented in the Statistical
      Parametric Mapping software. WMLs were inversely correlated with GM volume, with
      the greatest volume loss in the frontal cortex. Age-related atrophy was observed
      in the hippocampus and posterior cingulate cortex. Regression analyses revealed
      links among age, APOE*4 allele, hypertension, WMLs, GM volume, and digit symbol
      substitution test scores. Both advancing age and hypertension predict higher WML
      load, which is itself associated with GM atrophy. Longitudinal data are needed to
      confirm the temporal sequence of events leading to a decline in cognitive
      function.

PMID- 21943961
TI  - When you dislike patients, pain is taken less seriously.
AB  - This study examined the influence of patients' likability on pain estimations
      made by observers. Patients' likability was manipulated by means of an evaluative
      conditioning procedure: pictures of patients were combined with either positive,
      neutral, or negative personal traits. Next, videos of the patients were presented
      to 40 observers who rated the pain. Patients were expressing no, mild-, or high
      intensity pain. Results indicated lower pain estimations as well as lower
      perceptual sensitivity toward pain (i.e., lower ability to discriminate between
      varying levels of pain expression) with regard to patients who were associated
      with negative personal traits. The effect on pain estimations was only found with
      regard to patients expressing high-intensity pain. There was no effect on
      response bias (i.e., the overall tendency to indicate pain). These findings
      suggest that we take the pain of patients we do not like less seriously than the
      pain of patients we like.

PMID- 21943962
TI  - Intraoperative occlusion of left coronary ostium after aortic repair detected by
      transesophageal echocardiography.

PMID- 21943963
TI  - Simplified nonresectional leaflet remodeling mitral valve repair for degenerative
      mitral regurgitation.

PMID- 21943964
TI  - Clinical trials and decision-making strategies for optimal treatment of relapsed
      ovarian cancer.
AB  - The proportion of patients with advanced ovarian cancer who relapse has remained
      high and fairly constant over the last decade. Choosing treatment for recurrent
      ovarian cancer is complex. Many active therapeutic agents are available, and
      there are challenges in defining the optimal timing and sequencing of treatments.
      Furthermore, the explosion in the number of biological agents presents additional
      challenges in identifying their activity and place in the pathway of treatment.
      Establishing optimal treatment as monotherapy, or in combination with
      chemotherapy, or as maintenance treatment requires new approaches to trial
      design, selecting meaningful endpoints and conducting carefully conducted trials
      with translational studies. Patients with relapsed ovarian cancer can now survive
      several years; the aim is to increase this further.

PMID- 21943965
TI  - The role of targeted therapy in ovarian cancer.
AB  - Ovarian cancer is the second most common gynaecological malignancy and the
      leading cause of death from gynaecological cancer. Although in some cases
      treatment is initially effective, there is a considerable risk of disease
      recurrence and resistance to therapy. Therapies targeting molecular alterations
      in tumours offer the promise of significantly improved treatment. So far, the
      most promising targeted agents are angiogenesis inhibitors and PARP inhibitors.
      Here, we review the various targeted therapeutic approaches under clinical
      investigation in phase I and II trials of ovarian cancer and the challenges
      facing their future success in the clinic.

PMID- 21943966
TI  - Chairperson's introduction: The goal of cancer screening is to detect cancer when
      it is early and treatable, if not curable.

PMID- 21943967
TI  - Breast cancer screening.

PMID- 21943968
TI  - Lung cancer screening.

PMID- 21943969
TI  - Screening for colorectal cancer: sense and sensibilities.
AB  - PURPOSE: In this paper we investigate the reasons for non-participation in a
      trial programme for colorectal cancer (CRC) screening in Flanders. Besides, the
      feasibility and possibilities of a full-blown screening programme in Flanders are
      examined, given the context of a low participation rate in breast cancer
      screening. METHODS: A trial programme for CRC screening was set up for all
      average-risk persons aged 50 to 74 years in three Flemish regions to obtain
      information about potential participation rates, and to compare two invitation
      strategies. Faecal samples were analysed for precursors of CRC using an
      immunochemical faecal occult blood test (iFOBT). A questionnaire was administered
      to participants and non-participants of the trial programme to find out whether
      and to what extent the taking of a sample of one's own stool is a taboo. This
      could be of great importance concerning the participation rate. RESULTS: In
      total, 19,542 persons were invited to participate in the trial programme for CRC
      screening, of whom 18,541 were found to be eligible. The overall participation
      rate was 44.3%. The three regions varied in participation rates: with 60.9% in
      the most rural region to 34.3% in the most urban region. Of 2,000 questionnaires
      sent to participants, 1,385 were returned (69.3%). The response in the non
      participants was 43.2%i (691 questionnaires of 1,600 returned). CONCLUSIONS: A
      population-based screening programme for colorectal cancer by means of an iFOBT
      proves to be feasible, since adequate participation rates were obtained and
      because of the absence of a 'stool taboo' in Flanders.

PMID- 21943970
TI  - Screening for prostate cancer.

PMID- 21943971
TI  - Glossary of essential terms used in cancer screening.

PMID- 21943972
TI  - Chairperson's introduction: Prostate cancer (PCa) is the most frequently detected
      cancer in the European Union in men above 50 years of age.

PMID- 21943973
TI  - What is the pathophysiology of a hormone-resistant prostate tumour?

PMID- 21943975
TI  - Novel treatments for castration-resistant prostate cancer.
AB  - The contemporary management of metastatic castration-resistant prostate cancer
      (mCRPC) is evolving dramatically. Understanding the biology of this disease,
      positive phase III studies and approvals for 4 novel agents in the US in 2010 and
      shortly in Europe have dramatically changed the therapeutic landscape.

PMID- 21943974
TI  - Continued targeting of androgen receptor signalling: a rational and efficacious
      therapeutic strategy in metastatic castration-resistant prostate cancer.

PMID- 21943976
TI  - Experimental models for the development of new medical treatments in prostate
      cancer.

PMID- 21943977
TI  - Chairperson's introduction: Cancer affects not only the afflicted individual, but
      the individual's family as well.

PMID- 21943978
TI  - Paediatric outcomes following in utero exposure to the diagnosis and treatment of
      maternal malignancy.

PMID- 21943979
TI  - Radiotherapy in patients with metastatic breast cancer.

PMID- 21943980
TI  - Adverse reproductive effects of treatment for cancer in childhood and
      adolescence.

PMID- 21943981
TI  - Psychological impact of having a parent with cancer.

PMID- 21943982
TI  - 2010 Consensus on Lung Cancer, new clinical recommendations and current status of
      biomarker assessment--first-line therapy.

PMID- 21943983
TI  - Second-line treatment options in advanced non-small cell lung cancer.

PMID- 21943984
TI  - Small cell lung cancer: new clinical recommendations and current status of
      biomarker assessment.
AB  - Small-cell lung carcinomas (SCLC) represent 15-18% of all lung cancers. As SCLC
      has a high propensity for early metastatic dissemination, less than a third of
      patients have limited disease (T0-1N0-3M0). The new TNM classification should now
      be used also for SCLC. Platin- and etoposide-based chemotherapy is the
      cornerstone treatment. Response rates to both chemotherapy and radiotherapy are
      impressive but relapses are frequent. The current state-of-the-art treatment for
      MO patients involves platin-etoposide-based chemotherapy, combined with early
      thoracic radiotherapy. Because of the high risk of brain metastases, prophylactic
      cranial irradiation is indicated in responders and should be part of the standard
      management. The 5-year survival rate may reach 25% in MO patients, but does not
      exceed 10% at 2 years in metastatic patients. Most patients relapse within the
      first two years, and there are few treatment options in second line as opposed to
      NSCLC. Many issues are subject for further clinical research such as the biology
      of this disease to better identify pathways that could be targeted with new
      drugs, optimisation of systemic treatments and radiotherapy. Pursuing clinical
      trials at all stages constitutes a challenge for thoracic researchers and
      oncologists.

PMID- 21943985
TI  - Role of hormonal manipulations in patients with hormone-sensitive metastatic
      breast cancer.

PMID- 21943986
TI  - Breast cancer in the elderly: different treatment modalities.

PMID- 21943987
TI  - Management of local recurrence of rectal cancer.

PMID- 21943988
TI  - Management of early-stage non-small-cell lung cancer (NSCLC).

PMID- 21943989
TI  - What are the expected developments in the medical treatment of bladder cancer.

PMID- 21943990
TI  - Radiotherapy of prostate cancer.

PMID- 21943991
TI  - Current treatment of nasopharyngeal carcinoma.

PMID- 21943992
TI  - To PET or not to PET: what are the indications?

PMID- 21943993
TI  - Advances in the treatment of multiple myeloma.

PMID- 21943994
TI  - How to personalise treatment in early breast cancer.

PMID- 21943995
TI  - Current standards and new trends in the primary treatment of colorectal cancer.

PMID- 21943996
TI  - Thymoma update 2011.

PMID- 21943997
TI  - Adjuvant treatments for locally advanced prostate cancer.

PMID- 21943998
TI  - Basic science of lung cancer.

PMID- 21943999
TI  - New technology in radiotherapy.

PMID- 21944000
TI  - Growth factor receptor-related therapy for gastric cancer.

PMID- 21944001
TI  - Uterine sarcomas: a multidisciplinary challenge.

PMID- 21944002
TI  - Targeted therapy in refractory thyroid cancer.

PMID- 21944003
TI  - Perioperative treatment of high-risk penile squamous cell carcinoma (SCC).

PMID- 21944004
TI  - DNA repair as treatment target.

PMID- 21944005
TI  - Current approaches to adjuvant therapy of melanoma.

PMID- 21944006
TI  - Medulloblastoma.

PMID- 21944007
TI  - Male breast cancer--neglected tumour.

PMID- 21944008
TI  - Skin-sparing mastectomy.

PMID- 21944009
TI  - Radiation therapy and radioisotopes for bone metastases: what is their real
      benefit?

PMID- 21944010
TI  - Review of the incidence, prevalence, mortality and causative factors for lung
      cancer in Europe.

PMID- 21944011
TI  - Cancer and pregnancy: what should we know about the management with systemic
      treatment of pregnant women with cancer?
AB  - The incidence of cancer during pregnancy is a rare phenomenon and is estimated to
      occur in 1:1000 pregnancies. This co-existence is likely to rise since the delay
      of childbearing to the later reproductive age is nowadays more common in
      families. The most frequent malignancies diagnosed during pregnancy are breast
      cancer, cervical cancer, haematological malignancies (lymphomas and acute
      leukaemias) and melanoma. Less common tumours are gastrointestinal, urological
      and lung cancers [1].

PMID- 21944012
TI  - Current standard and trends in oesophageal cancer.

PMID- 21944013
TI  - Active surveillance and radical prostatectomy.

PMID- 21944014
TI  - Anaplastic gliomas: an emerging entity.

PMID- 21944015
TI  - Emergencies in palliative care.

PMID- 21944016
TI  - Geriatrics and haematological malignancies: is comprehensive geriatric assessment
      a useful tool?

PMID- 21944017
TI  - Developing effective cancer vaccines.

PMID- 21944018
TI  - Ewing sarcoma treatment.

PMID- 21944019
TI  - Triple negative breast cancer: a heterogeneous subgroup defined by what it is
      not.

PMID- 21944020
TI  - Combining molecular targeted therapeutics (MTT) and radiotherapy: MTT and MTD.

PMID- 21944021
TI  - Systemic treatment of non-small-cell lung cancer.

PMID- 21944022
TI  - Adjuvant treatment of pancreatic cancer.

PMID- 21944023
TI  - The role of chemotherapy and targeted agents in patients with metastatic breast
      cancer.
AB  - Metastatic breast cancer has always been a challenging disease to treat, with
      cytotoxic chemotherapy often being deemed a merely palliative treatment that is
      given to relieve cancer-related symptoms. However with the introduction of more
      effective systemic therapies over the last two decades, recently we have
      witnessed substantial improvements in clinical outcomes such that many patients
      now live with metastatic secondary breast cancer for many years. Various
      different cytotoxics are used in clinical practice, and targeted biological
      therapeutics have an increasing role to play in the management of different
      breast cancer subtypes. The appropriate use of these different systemic
      therapeutics has been one of the principal reasons for the continued improvement
      in clinical outcomes for women with advanced breast cancer, including a probable
      substantial impact on overall survival.

PMID- 21944024
TI  - Translational genomics in breast cancer.

PMID- 21944025
TI  - Overview of the role of laparoscopic surgery in cancer management.

PMID- 21944026
TI  - Soft tissue sarcomas: are all soft tissue sarcomas treated with the same drugs?

PMID- 21944027
TI  - Chairperson's introduction: Despite significant advances in the diagnosis and
      treatment of breast cancer, approximately one third of patients still develop,
      and subsequently die from metastatic breast disease.

PMID- 21944028
TI  - Chairperson's introduction: Survival of patients with metastatic colorectal
      cancer has dramatically improved over the last decade. .

PMID- 21944029
TI  - Neoadjuvant chemotherapy for non-/resectable metastases.

PMID- 21944030
TI  - The role of surgery in metastatic breast cancer.
AB  - Some of the patients who present with breast cancer already have distant
      metastatic disease. According to recent literature, these patients may benefit
      from resection of the breast tumour. One explanation for the effect of this
      resection is that reducing the tumour load influences metastatic growth. Results
      of future randomised controlled trials should indicate whether surgery of the
      breast tumour truly improves survival. Selected patients could even benefit from
      metastasectomy of liver and lung metastases; survival seems to improve and these
      procedures seldom lead to major complications. When metastasectomy is not
      possible, minimally invasive techniques can be used in selected patients for the
      treatment of breast cancer liver metastases, radiofrequency ablation (RFA) being
      discussed most in the literature. Patients with locally advanced breast cancer
      are treated multidisciplinarily and with curative intent. Part of the treatment
      is surgery to reduce tumour load. Regarding treatment of the axilla, in a
      clinically negative axilla sentinel node biopsy is advised before neoadjuvant
      treatment; an axillary lymph node dissection is not warranted. In local
      recurrence, surgery is the primary treatment. Axillary staging can be done in
      patients with a previous negative sentinel node biopsy. Regional recurrence after
      breast-conserving surgery or mastectomy is treated with surgery followed by
      radiotherapy.

PMID- 21944031
TI  - Surgery of the primary in stage IV colorectal cancer with unresectable
      metastases.
AB  - Surgery plays an important role in the treatment of patients with limited
      metastatic disease of colorectal cancer (CRC). Long term survival and cure is
      reported in 20-50% of highly selected patients with oligometastatic disease who
      underwent surgery. This paper describes the role of surgery of the primary tumour
      in patients with unresectable stage IV colorectal cancer. Owing to the increased
      efficacy of chemotherapeutic regimens in stage IV colorectal cancer,
      complications from unresected primary tumours are relatively infrequent. The risk
      of emergency surgical intervention is less than 15% in patients with synchronous
      metastatic disease who are treated with chemotherapy. Therefore, there is a
      tendency among surgeons not to resect the primary tumour in case of unresectable
      metastases. However, it is suggested that resection of the primary tumour in case
      of unresectable metastatic disease might influence overall survival. All studies
      described in the literature (n = 24) are non-randomised and the majority is
      single-centre and retrospective of nature. Most studies are in favour of
      resection of the primary tumour in patients with symptomatic lesions. In
      asymptomatic patients the results are less clear, although median overall
      survival seems to be improved in resected patients in the majority of studies.
      The major drawback of all these studies is that primarily patients with a better
      performance status and better prognosis (less metastatic sites involved) are
      being operated on. Another limitation of these studies is that few if any data on
      the use of systemic therapy are presented, which makes it difficult to assess the
      relative contribution of resection on outcome. Prospective studies on this topic
      are warranted, and are currently being planned. CONCLUSION: Surgery of the
      primary tumour in patients with synchronous metastasised CRC is controversial,
      although data from the literature suggest that resection might be a positive
      prognostic factor for survival. Therefore prospective studies on the value of
      resection in this setting are required.

PMID- 21944032
TI  - The treatment of patients with low tumour burden and/or slow growing disease.

PMID- 21944033
TI  - Re-challenge and the concept of lines of therapy in metastatic colorectal cancer.

PMID- 21944034
TI  - Chairperson's introduction: Surgical skills, especially in the upper abdomen,
      remain pivotal in the treatment of advanced ovarian cancer.

PMID- 21944035
TI  - Primary surgery or neoadjuvant chemotherapy followed by interval debulking
      surgery in advanced ovarian cancer.
AB  - Advanced ovarian cancer has a poor prognosis. De-bulking surgery and platinum
      based chemotherapy are the cornerstones of the treatment. Primary debulking
      surgery has been the standard of care in advanced ovarian cancer. Recently a new
      strategy with neoadjuvant chemotherapy followed by interval debulking surgery has
      been developed. In a recently published randomised trial of the EORTC-NCIC
      (European Organisation for Research and Treatment of Cancer - National Cancer
      Institute Canada) in patients with extensive stage IIIc and IV ovarian cancer it
      was shown that the survival was similar for patients randomised to neoadjuvant
      chemotherapy followed by interval debulking compared to primary debulking
      surgery, followed by chemotherapy. The post-operative complications and mortality
      rates were lower after interval debulking than after primary debulking surgery.
      The most important independent prognostic factor for overall survival was no
      residual tumour after primary or interval debulking surgery. In some patients
      obtaining the goal of no residual tumour at interval debulking is difficult due
      to chemotherapy-induced fibrosis. On the other hand the patients randomised had
      very extensive stage IIIc and IV disease and in patients with metastases smaller
      than 5 cm the survival tended to be better after primary debulking surgery.
      Hence, selection of the correct patients with stage IIIc or IV ovarian cancer for
      primary debulking or neoadjuvant chemotherapy followed by interval debulking
      surgery is important. Besides imaging with CT, diffusion MRI and/or PET-CT, also
      laparoscopy can play an important role in the selection of patients. It should be
      emphasised that the group of patients included in this study had extensive stage
      IIIc or IV disease. Surgical skills, especially in the upper abdomen, remain
      pivotal in the treatment of advanced ovarian cancer. However, very aggressive
      surgery should be tailored according to the general condition and extent of the
      disease of the patients. Otherwise, this type of aggressive surgery will result
      in unnecessary postoperative morbidity and mortality without improving survival.
      Hence, neoadjuvant chemotherapy should not be an easy way out, but is in some
      patients with stage IIIc or IV ovarian cancer a better alternative treatment
      option than primary debulking. According to the current treatment algorithm at
      the University Hospitals Leuven about 50% of the patients with stage IIIc or IV
      ovarian cancer are selected for neoadjuvant chemotherapy.

PMID- 21944036
TI  - First line therapy: have we made any improvement?

PMID- 21944037
TI  - It is fascinating to see how nowadays more and more knowledge of the molecular
      biological characteristics of the tumour lead to individualisation with surgery,
      radiotherapy and systemic treatment for patients with a malignancy. Introduction.

PMID- 21944038
TI  - Assessment of aquatic experimental versus predicted and extrapolated chronic
      toxicity data of four structural analogues.
AB  - The present study was developed to assess the chronic toxicity predictions and
      extrapolations for a set of chlorinated anilines (aniline (AN), 4-chloroaniline
      (CA), 3,5-dichloroaniline (DCA) and 2,3,4-trichloroaniline (TCA)). Daphnia magna
      21 d chronic experimental data was compared to the chronic toxicity predictions
      made by the US EPA ECOSAR QSAR tools and to acute-to-chronic extrapolations.
      Additionally, Species Sensitivity Distributions (SSDs) were constructed to assess
      the chronic toxicity variability among different species and to investigate the
      acute versus chronic toxicity in a multi-species context. Since chlorinated
      anilines are structural analogues with a designated polar narcotic mode of
      action, similar toxicity responses were assumed. However, rather large
      interchemical and interspecies differences in toxicity were observed. Compared to
      the other three test compounds, TCA exposure had a significantly larger impact on
      growth and reproduction of D. magna. Furthermore, this study illustrated that
      QSARs or a fixed ACR are not able to account for these interchemical and
      interspecies differences. Consequently, ECOSAR was found to be inadequate to
      predict the chronic toxicity of the anilines and the use of a fixed ACR (of 10)
      led to under of certain species. The experimental ACRs determined in D. magna
      were substantially different among the four aromatic amines (ACR of 32 for AN,
      16.9 for CA, 5.7 for DCA and 60.8 for TCA). Furthermore, the SSDs illustrated
      that Danio rerio was rather insensitive to AN in comparison to another fish
      species, Phimphales promelas. It was therefore suggested that available toxicity
      data should be used in an integrative multi-species way, rather than using
      individual-based toxicity extrapolations. In this way, a relevant overview of the
      differences in species sensitivity is given, which in turn can serve as the basis
      for acute to chronic extrapolations.

PMID- 21944039
TI  - Reprint of: Removal and formation of chlorinated triclosan derivatives in
      wastewater treatment plants using chlorine and UV disinfection.
AB  - Triclosan, a common antimicrobial agent, may react during the disinfection of
      wastewater with free chlorine to form three chlorinated triclosan derivatives
      (CTDs). This is of concern because the CTDs may be photochemically transformed to
      tri- and tetra-chlorinated dibenzo-p-dioxins when discharged into natural waters.
      In this study, wastewater influent, secondary (pre-disinfection) effluent, and
      final (post-disinfection) effluent samples were collected on two occasions each
      from two activated sludge wastewater treatment plants, one using chlorine
      disinfection and one using UV disinfection. Concentrations of triclosan and three
      CTDs were determined using ultra performance liquid chromatography-triple
      quadrupole mass spectrometry with isotope dilution methodology. Triclosan and the
      CTDs were detected in every influent sample at levels ranging from 453 to 4530
      and 2 to 98 ng L(-1), respectively, though both were efficiently removed from the
      liquid phase during activated sludge treatment. Triclosan concentrations in the
      pre-disinfection effluent ranged from 36 to 212 ng L(-1), while CTD
      concentrations were below the limit of quantification (1 ng L(-1)) for most
      samples. In the treatment plant that used chlorine disinfection, triclosan
      concentrations decreased while CTDs were formed during chlorination, as evidenced
      by CTD levels as high as 22 ng L(-1) in the final effluent. No CTDs were detected
      in the final effluent of the treatment plant that used UV disinfection. The total
      CTD concentration in the final effluent of the chlorinating treatment plant
      reached nearly one third of the triclosan concentration, demonstrating that the
      chlorine disinfection step played a substantial role in the fate of triclosan in
      this system.

PMID- 21944040
TI  - Reprint of: Concentrations, distribution, and bioaccumulation of synthetic musks
      in the Haihe River of China.
AB  - Seven typical synthetic musks (SMs) in the samples from the surface water,
      sediment and fish of the Haihe River were measured. The SM concentrations in the
      sediment and surface water of the Haihe River were significantly lower than those
      in the Dagu Drainage River and Chentaizi Drainage River (p<0.05). Along the flow
      direction, the SM concentrations in surface water and sediment tended to increase
      from the upstream to the downstream of Dagu Drainage River. The Bioaccumulation
      factors (BAFs) of galaxolide (HHCB) and tonalide (AHTN) were calculated at high
      levels in the muscles of crucian carp, common carp, and silver carp. Most of the
      biota-sediment accumulation factors (BSAFs) for HHCB and AHTN were higher than
      1.7, suggesting magnification possibly exist in the musk bioaccumulations of the
      three fishes in the Haihe River. No significant differences in HHCB/AHTN ratios
      were observed among the water, fish, and sediment samples (p>0.05). However, the
      HHCB/AHTN values in the Haihe River were much lower than those in the Dagu
      Drainage River and Chentaizi Drainage River (p<0.05). Compared with several
      typical persistent organic pollutants (POPs), the musk concentrations were higher
      or comparable in the Haihe River.

PMID- 21944041
TI  - Impact of biochar application to a Mediterranean wheat crop on soil microbial
      activity and greenhouse gas fluxes.
AB  - Biochar has been recently proposed as a management strategy to improve crop
      productivity and global warming mitigation. However, the effect of such approach
      on soil greenhouse gas fluxes is highly uncertain and few data from field
      experiments are available. In a field trial, cultivated with wheat, biochar was
      added to the soil (3 or 6 kg m(-2)) in two growing seasons (2008/2009 and
      2009/2010) so to monitor the effect of treatments on microbial parameters 3
      months and 14 months after char addition. N(2)O, CH(4) and CO(2) fluxes were
      measured in the field during the first year after char addition. Biochar
      incorporation into the soil increased soil pH (from 5.2 to 6.7) and the rates of
      net N mineralization, soil microbial respiration and denitrification activity in
      the first 3 months, but after 14 months treated and control plots did not differ
      significantly. No changes in total microbial biomass and net nitrification rate
      were observed. In char treated plots, soil N(2)O fluxes were from 26% to 79%
      lower than N(2)O fluxes in control plots, excluding four sampling dates after the
      last fertilization with urea, when N(2)O emissions were higher in char treated
      plots. However, due to the high spatial variability, the observed differences
      were rarely significant. No significant differences of CH(4) fluxes and field
      soil respiration were observed among different treatments, with just few
      exceptions. Overall the char treatments showed a minimal impact on microbial
      parameters and GHG fluxes over the first 14 months after biochar incorporation.

PMID- 21944042
TI  - Reprint of: Temporal trends of polyfluoroalkyl compounds (PFCs) in liver tissue
      of grey seals (Halichoerus grypus) from the Baltic Sea, 1974-2008.
AB  - Temporal trends of polyfluoroalkyl compounds (PFCs) were examined in grey seal
      (Halichoerus grypus) liver from the Baltic Sea over a period of 35 years (1974
      2008). In total, 17 of 43 PFCs were found, including the perfluoroalkyl
      sulfonates (C(4)-C(10) PFSAs), perfluorooctanesulfinate (PFOSi), long chain
      perfluoroalkyl carboxylates (C(7)-C(14) PFCAs), and perfluoroalkyl sulfonamides
      (i.e., perfluorooctane sulfonamide (FOSA) and N-ethyl perfluorooctane sulfonamide
      (EtFOSA)), whereas saturated and unsaturated fluorotelomer carboxylates, shorter
      chain PFCAs and perfluoroalkyl phosphonic acids were not detected.
      Perfluorooctane sulfonate (PFOS) was the predominant compound (9.57-1444 ng g(-1)
      wet weight (ww)), followed by perfluorononanoate (PFNA, 0.47-109 ng g(-1) ww).
      C(6)-C(8) PFSAs, PFOSi and C(7)-C(13) PFCAs showed statistically significant
      increasing concentrations between 1974 and 1997, with a peak in 1997 and then
      decreased or levelled off (except for C(12) and C(13) PFCAs). FOSA had a
      different temporal trend with a maximum in 1989 followed by significant
      decreasing concentrations until 2008. Toxicological implications for grey seals
      are limited, but the maximal PFOS concentration found in this study was about 40
      times lower than the predicted lowest observed effect concentrations (LOEC). The
      statistically significant decreasing concentrations or levelling off for several
      PFCs in the relative closed marine ecosystem of the Baltic Sea indicate a rapidly
      responding to reduced emissions to the marine environment. However, the high
      concentrations of PFOS and continuing increasing concentrations of the longer
      chain PFCAs (C(12)-C(14)) shows that further work on the reduction of
      environmental emissions of PFCs are necessary.

PMID- 21944043
TI  - The joint effects of sulfonamides and their potentiator on Photobacterium
      phosphoreum: differences between the acute and chronic mixture toxicity
      mechanisms.
AB  - Organisms are typically exposed to mixtures of chemicals over long periods of
      time; thus, chronic mixture toxicity analysis is the best way to perform risk
      assessment in regards to organisms. However, most studies focus on the acute
      mixture toxicity. To investigate the difference between chronic mixture toxicity
      and acute mixture toxicity, Photobacterium phosphoreum were exposed to chronic
      (24 h exposure) and acute (15 min exposure) toxicity of single sulfonamide (SA)
      and their potentiator (trimethoprim, TMP), both individually and mixtures (SA
      with TMP). A comparison of chronic vs. acute mixture toxicity revealed the
      presence of an interesting phenomenon, that is, that the joint effects vary with
      the duration of exposure; the acute mixture toxicity was antagonistic, whereas
      the chronic mixture toxicity was synergistic. Based on the approach of
      Quantitative Structure Activity Relationships (QSARs) and molecular docking, this
      phenomenon was proved to be caused by the presence of two points of dissimilarity
      between the acute and chronic mixture toxicity mechanism: (1) the receptor
      protein of SAs in acute toxicity was Luc, while in chronic toxicity it was Dhps,
      and (2) there is a difference between actual concentration of binding-Luc in
      acute toxicity and individual binding-Dhps in chronic toxicity. This deep insight
      into the difference between chronic and acute mixture toxicity will benefit
      environmental science, medical science, and other disciplines. The existence of
      these differences poses a challenge for the assessment of routine combinations in
      medicine, risk assessment, and mixture pollutant control, in which, previously,
      only a synergistic effect has been observed between SA and their potentiator.

PMID- 21944045
TI  - Denisova admixture and the first modern human dispersals into Southeast Asia and
      Oceania.
AB  - It has recently been shown that ancestors of New Guineans and Bougainville
      Islanders have inherited a proportion of their ancestry from Denisovans, an
      archaic hominin group from Siberia. However, only a sparse sampling of
      populations from Southeast Asia and Oceania were analyzed. Here, we quantify
      Denisova admixture in 33 additional populations from Asia and Oceania. Aboriginal
      Australians, Near Oceanians, Polynesians, Fijians, east Indonesians, and Mamanwa
      (a "Negrito" group from the Philippines) have all inherited genetic material from
      Denisovans, but mainland East Asians, western Indonesians, Jehai (a Negrito group
      from Malaysia), and Onge (a Negrito group from the Andaman Islands) have not.
      These results indicate that Denisova gene flow occurred into the common ancestors
      of New Guineans, Australians, and Mamanwa but not into the ancestors of the Jehai
      and Onge and suggest that relatives of present-day East Asians were not in
      Southeast Asia when the Denisova gene flow occurred. Our finding that descendants
      of the earliest inhabitants of Southeast Asia do not all harbor Denisova
      admixture is inconsistent with a history in which the Denisova interbreeding
      occurred in mainland Asia and then spread over Southeast Asia, leading to all its
      earliest modern human inhabitants. Instead, the data can be most parsimoniously
      explained if the Denisova gene flow occurred in Southeast Asia itself. Thus,
      archaic Denisovans must have lived over an extraordinarily broad geographic and
      ecological range, from Siberia to tropical Asia.

PMID- 21944046
TI  - Mutations in iron-sulfur cluster scaffold genes NFU1 and BOLA3 cause a fatal
      deficiency of multiple respiratory chain and 2-oxoacid dehydrogenase enzymes.
AB  - Severe combined deficiency of the 2-oxoacid dehydrogenases, associated with a
      defect in lipoate synthesis and accompanied by defects in complexes I, II, and
      III of the mitochondrial respiratory chain, is a rare autosomal recessive
      syndrome with no obvious causative gene defect. A candidate locus for this
      syndrome was mapped to chromosomal region 2p14 by microcell-mediated chromosome
      transfer in two unrelated families. Unexpectedly, analysis of genes in this area
      identified mutations in two different genes, both of which are involved in [Fe-S]
      cluster biogenesis. A homozygous missense mutation, c.545G>A, near the splice
      donor of exon 6 in NFU1 predicting a p.Arg182Gln substitution was found in one of
      the families. The mutation results in abnormal mRNA splicing of exon 6, and no
      mature protein could be detected in fibroblast mitochondria. A single base-pair
      duplication c.123dupA was identified in BOLA3 in the second family, causing a
      frame shift that produces a premature stop codon (p.Glu42Argfs(*)13).
      Transduction of fibroblast lines with retroviral vectors expressing the
      mitochondrial, but not the cytosolic isoform of NFU1 and with isoform 1, but not
      isoform 2 of BOLA3 restored both respiratory chain function and oxoacid
      dehydrogenase complexes. NFU1 was previously proposed to be an alternative
      scaffold to ISCU for the biogenesis of [Fe-S] centers in mitochondria, and the
      function of BOLA3 was previously unknown. Our results demonstrate that both play
      essential roles in the production of [Fe-S] centers for the normal maturation of
      lipoate-containing 2-oxoacid dehydrogenases, and for the assembly of the
      respiratory chain complexes.

PMID- 21944047
TI  - Mutations in CSTA, encoding Cystatin A, underlie exfoliative ichthyosis and
      reveal a role for this protease inhibitor in cell-cell adhesion.
AB  - Autosomal-recessive exfoliative ichthyosis presents shortly after birth as dry,
      scaly skin over most of the body with coarse peeling of nonerythematous skin on
      the palms and soles, which is exacerbated by excessive moisture and minor trauma.
      Using whole-genome homozygosity mapping, candidate-gene analysis and deep
      sequencing, we have identified loss-of-function mutations in the gene for
      protease inhibitor cystatin A (CSTA) as the underlying genetic cause of
      exfoliative ichthyosis. We found two homozygous mutations, a splice-site and a
      nonsense mutation, in two consanguineous families of Bedouin and Turkish origin.
      Electron microscopy of skin biopsies from affected individuals revealed that the
      level of detachment occurs in the basal and lower suprabasal layers. In addition,
      in vitro modeling suggests that in the absence of cystatin A protein, there is a
      cell-cell adhesion defect in human keratinocytes that is particularly prominent
      when cells are subject to mechanical stress. We show here evidence of a key role
      for a protease inhibitor in epidermal adhesion within the lower layers of the
      human epidermis.

PMID- 21944048
TI  - Accuracy and reproducibility of 3D-CT measurements for early response assessment
      of chemoradiotherapy in patients with oesophageal cancer.
AB  - BACKGROUND: Chemoradiotherapy is increasingly applied in patients with
      oesophageal cancer. The aim of the present study was to determine whether 3D-CT
      volumetry is able to differentiate between responding and non-responding
      oesophageal tumours early in the course of neoadjuvant chemoradiotherapy.
      PATIENTS AND METHODS: Serial CT before and after two weeks of neoadjuvant
      chemoradiotherapy was performed in the multimodality treatment arm of a
      randomised trial including patients with oesophageal carcinoma. CT response was
      measured with the change in tumour volume between baseline and after 14 days of
      neoadjuvant therapy. Receiver Operating Characteristic (ROC) analysis was used to
      evaluate the ability of 3D-CT as an early imaging marker of response. RESULTS: CT
      response analysis was performed in 39 patients, of whom 26 patients were
      histopathological responders. Median tumour volume increased between baseline and
      after 14 days of chemoradiotherapy in histopathological responders as well as in
      non-responders, though changes were not statistically significant. The area under
      the ROC curve was 0.71. CONCLUSION: Tumour volume changes after 14 days of
      neoadjuvant chemoradiotherapy as measured by 3D-CT were not associated with
      histopathological tumour response. CT volumetry should not be used for early
      response assessment in patients with potentially curable oesophageal cancer
      treated with neoadjuvant chemoradiotherapy.

PMID- 21944049
TI  - Variation in case-mix between hospitals treating colorectal cancer patients in
      the Netherlands.
AB  - AIMS: The purpose of this study was to determine how expected mortality based on
      case-mix varies between colorectal cancer patients treated in non-teaching,
      teaching and university hospitals, or high, intermediate and low-volume hospitals
      in the Netherlands. MATERIAL AND METHODS: We used the database of the Dutch
      Surgical Colorectal Audit 2010. Factors predicting mortality after colon and
      rectum carcinoma resections were identified using logistic regression models.
      Using these models, expected mortality was calculated for each patient. RESULTS:
      8580 patients treated in 90 hospitals were included in the analysis. For colon
      carcinoma, hospitals' expected mortality ranged from 1.5 to 14%. Average expected
      mortality was lower in patients treated in high-volume hospitals than in low
      volume hospitals (5.0 vs. 4.3%, p < 0.05). For rectum carcinoma, hospitals
      expected mortality varied from 0.5 to 7.5%. Average expected mortality was higher
      in patients treated in non-teaching and teaching hospitals than in university
      hospitals (2.7 and 2.3 vs. 1.3%, p < 0.01). Furthermore, rectum carcinoma
      patients treated in high-volume hospitals had a higher expected mortality than
      patients treated in low-volume hospitals (2.6 vs. 2.2% p < 0.05). We found no
      differences in risk-adjusted mortality. CONCLUSIONS: High-risk patients are not
      evenly distributed between hospitals. Using the expected mortality as an
      integrated measure for case-mix can help to gain insight in where high-risk
      patients go. The large variation in expected mortality between individual
      hospitals, hospital types and volume groups underlines the need for risk
      adjustment when comparing hospital performances.

PMID- 21944050
TI  - Overexpression of cyclin E isoforms correlates with poor prognosis in rectal
      cancer.
AB  - AIMS: To investigate the expression of cyclin E isoforms in rectal cancer and its
      relations to clinicopathological factors and survival. MATERIALS AND METHODS:
      Cyclin E expression was assessed by Western blot in 360 resected rectal cancer
      patients of stage I to III. Multivariate analysis was applied to indicate the
      independent prognostic markers in this cohort. RESULTS: Nineteen percent, 24% or
      29% patients exhibited elevated levels of full-length (FL) cyclin E, low
      molecular-weight (LMW) cyclin E or total cyclin E in their tumors respectively.
      Significant correlation was observed between cyclin E expression with blood
      vessel invasion, deeply invasive tumors, histology grade and lymph node
      metastasis. Moreover, patients with high levels of LMW-cyclin E or total cyclin E
      had a poorer 5-year overall survival than did patients with low levels of LMW
      cyclin E or total cyclin E. In multivariate analysis, both the LMW-cyclin E and
      total cyclin E, but not FL-cyclin E, remained independent prognostic indicators
      in both patients with stage I to III and in those with early stage. Patients with
      elevated LMW- or total cyclin E levels had a hazard ratio for death from rectal
      cancer of 6.302 (95% CI, 1.903-17.81, p = 0.001) or 4.332 (95% CI, 1.298-16.362,
      p = 0.001). CONCLUSION: Overexpression of the LMW-cyclin E or total cyclin E is a
      strong predictor for poorer survival in patients with rectal cancer. Therefore,
      evaluating cyclin E expression may provide useful prognostic information for
      resectable rectal cancer patients.

PMID- 21944051
TI  - In vitro lipopolysaccharide treatment alters regulatory T cell properties in
      chickens.
AB  - The objective of this study was to identify the effect of in vitro
      lipopolysaccharide (LPS) treatment on regulatory T cells (Tregs) from chickens.
      Tregs had approximately 30-fold higher TLR 2-type 2 and six-fold higher TLR 4
      mRNA content than CD4+CD25- cells. Tregs were treated with either 0 or 1 MUg/ml
      LPS for 0, 2, and 4d. LPS treatment increased the IL-2 mRNA amount in Tregs at 2
      and 4d post-LPS treatment. LPS treatment increased the IL-10 mRNA amount in Tregs
      at 4d post-LPS treatment. The total live cell numbers were approximately two-fold
      higher at 2d and three-fold higher at 4d in the 1 MUg/ml LPS-treated groups than
      in the 0 MUg LPS-treated controls. LPS treatment abrogated suppressive properties
      of Tregs at 2d post-LPS treatment. At 4d post-LPS treatment, Tregs became
      supersuppressive. In conclusion, chicken Tregs are differentially activated to
      facilitate immune response during the early stage of inflammation and to
      facilitate immune suppression at a later stage of inflammation.

PMID- 21944052
TI  - [Doctor, with your knowledge of medicine and health care and me, tell me, what
      would you do in my place?].

PMID- 21944053
TI  - [Diagnosis and treatment of attention deficit/hyperactivity disorder: differences
      between clinical interview and psychometric testing].

PMID- 21944054
TI  - Study of the adhesion of neurodegenerative proteins on plasma-modified and coated
      polypropylene surfaces.
AB  - The inner polymeric surface of an ELISA titration well is plasma-modified and
      coated with different surfactant molecules. The titration of neurodegenerative
      proteins markers (prion, Tau and beta-synuclein), previously demonstrated as more
      efficient with such modified tubes, is related to the adhesion behaviour of these
      proteins and their corresponding capture antibodies. The adhesion process is
      studied in terms of anchoring and specific mechanisms. The proteins and
      antibodies binding onto such modified surfaces is related to the substrate
      hydrophilic character calculated from the angle contact measure, to the polymer
      surface charge measured through the streaming potential determination at
      different pH and the inner surface roughness determined from AFM images.
      Furthermore, the influence of the blocking agent used during the ELISA titration
      is also studied. 

PMID- 21944055
TI  - Balloon dilation for management of choanal atresia and stenosis.
AB  - OBJECTIVES: We describe our use of balloon dilation to repair choanal atresia in
      a series of patients. STUDY DESIGN: Case series. METHODS: We performed a
      retrospective review of patients who underwent repair of choanal atresia using
      dilation with high pressure, non-compliant airway balloons between January 2009
      and September 2010. For primary cases, balloon dilation was used in conjunction
      with transnasal endoscopic puncture, and repair of bony stenosis with backbiting
      forceps and microdebrider drill. RESULTS: 5 patients underwent balloon dilation
      repair of choanal atresia or stenosis. 4 patients presented for primary repair,
      with a mean age of 2.9 months. 1 patient presented at 10 years of age for
      revision repair several years after previous attempts performed elsewhere. The
      average number of procedures was 3.6, with an average of 2 balloon dilations.
      There were no complications stemming from balloon dilation. Follow-up ranged from
      3 to 24 months. All patients demonstrated choanal patency on last follow-up.
      CONCLUSIONS: This is a novel use of high pressure, non-compliant balloons. We
      found success in dilating membranous stenoses, post-repair granulation, and scar
      tissue in revision cases. Balloon dilation is an effective adjuvant tool for use
      in the repair of choanal atresia and stenosis.

PMID- 21944056
TI  - Propranolol for the treatment of subglottic hemangiomas.
AB  - INTRODUCTION: Infantile subglottic hemangiomas are rare causes of airway
      obstruction. They begin to proliferate at 1-2 months of age and can cause
      biphasic stridor with or without respiratory distress. Diagnosis requires direct
      visualization by direct laryngoscopy and bronchoscopy. Various therapeutic
      options have been utilized for treatment, including tracheotomy, open surgical
      excision, laser ablation, intralesional steroid injection, systemic steroids, and
      now oral propranolol. METHODS: We present a retrospective chart review of
      infantile subglottic hemangiomas over a 5-year span (January 2005-2010) at a
      tertiary care pediatric hospital. IRB approval was obtained, and charts were
      reviewed to find patients with subglottic hemangiomas, including patient
      characteristics, presentation, workup, medical and surgical management, and
      outcomes. A case presentation demonstrates diagnostic, management, and treatment
      strategies and dilemmas encountered. RESULTS: Nine patients were found to have
      infantile subglottic hemangiomas. Six of nine patients were treated with laser
      excision, with five of the six having localized subglottic hemangiomas. In 2009,
      three of four patients were initiated on propranolol as first-line treatment; the
      fourth had comorbidities which precluded this. Of the three, two showed
      improvement, while a third, who also had bearded hemangioma, required
      tracheotomy. DISCUSSION: Infantile subglottic hemangiomas are rare but essential
      in the differential diagnosis of biphasic stridor. Although propranolol has been
      effective in treating cutaneous and airway hemangiomas, our experience suggests
      that this is not consistent for subglottic hemangiomas. In an area where airway
      compromise can be lethal, we must extend caution and monitor these patients
      closely as they may require adjuvant therapy.

PMID- 21944057
TI  - A comparison of tympanometry with 226 Hz and 1000 Hz probe tones in children with
      Down syndrome.
AB  - BACKGROUND: For children with Down syndrome, the incidence of hearing loss may be
      as high as 78% [1], therefore the American Academy of Pediatrics recommends
      regular screening for the presence of hearing abnormalities. Tympanometry is used
      as an indication of middle ear pathology. In our experience, Down's patients'
      tympanograms do not always correlate with otoscopic findings. Down's patients
      have joint laxity, small ear canals, anterior tympanic membrane orientation and
      softer tissue composition, all factors thought to affect tympanogram results in
      infants. Because the use of the 1000 Hz tympanometry is widely recognized as
      standard procedure in the evaluation of infants aged 0-6 months, we propose it
      may have greater reliability in testing patients with Down syndrome. OBJECTIVE:
      Compare the results of visual inspection of the tympanic membrane by a Pediatric
      Otolaryngologist to the results of tympanometry at traditional probe tone (226
      Hz) and at the infant probe tone (1000 Hz). METHODS: Institutional Review Board -
      approved prospective study of 26 subject-ears in patients with Down syndrome aged
      6 months-18 years but recent stable middle ear/Eustachian tube function using
      physical examination and tympanometric probe tones at 226 Hz and 1000 Hz. Subject
      ears were examined with record of "clear of effusion," showed the presence of
      "fluid," or were to be "excluded." Blinded to ear exam results, tympanometry was
      then completed with record of which Jerger classification tympanogram was found
      at each frequency. RESULTS: Although the sensitivity of each test was 1, the
      specificity of the 1000 Hz tympanometry (100%) in this study was markedly
      improved compared to the specificity of the 226 Hz tympanometry (71%) (p=0.016).
      CONCLUSIONS: This pilot study demonstrated evidence that tympanometry in children
      with Down syndrome may be more reliable at 1000 Hz than at 226 Hz in detecting
      the presence of middle ear effusion beyond infancy. Use of the 1000 Hz probe tone
      yielded fewer false positives for disease (type B tympanograms in the setting of
      absent middle ear disease). Further studies of a larger patient population are
      needed to corroborate these results.

PMID- 21944058
TI  - Porous Fe3O4 nanoparticles: synthesis and application in catalyzing epoxidation
      of styrene.
AB  - A facile route was employed to synthesize porous magnetite via reaction of
      FeCl(3).6H(2)O with N(2)H(4).H(2)O in ethylene glycol without any structure
      directing agent. The resultant Fe(3)O(4) particles were characterized by
      transmission electron microscopy, N(2) adsorption, X-ray photoelectron
      spectroscopy, and thermal gravimetric analysis. It was demonstrated that the
      particle size varied in the range of 40-220 nm, and the pore size of particles
      was centered around 2 nm. The gases produced in the formation process of the
      particles played key role in the formation of the porous structure. The obtained
      porous magnetite was used as support to immobilize Au nanoparticles with size
      less than 2 nm with the assistance of L-cysteine. The as-prepared Fe(3)O(4)
      particles can effectively catalyze epoxidation of styrene, and the immobilization
      of Au nanoparticles on the Fe(3)O(4) support significantly improved the activity
      of the catalyst.

PMID- 21944059
TI  - Phosphate uptake by TiO2: batch studies and NMR spectroscopic evidence for
      multisite adsorption.
AB  - Systematic studies, combining batch experiments with NMR spectroscopic methods,
      are carried out for phosphate sorption on titanium dioxide (TiO(2)). It is found
      that phosphate sorption on TiO(2) decreases with increasing pH, whereas the
      phosphate uptake by TiO(2) increases with increasing ionic strength of the
      solution. In I <= 0.1 M, the sorption sharply increases and reaches a near
      maximum and then followed by little changes showing Langmuir-type behavior,
      whereas in I = 0.7 M, non-Langmuirian uptake becomes evident as equilibrium
      phosphate concentrations increase in solution. The sorption of phosphate on
      TiO(2) is rapid and mostly irreversible at pH 4.5 and 7.0. At pH 9.0, however,
      the phosphate sorption is initially reversible and followed by resorption of
      phosphate on TiO(2) at the system re-equilibration. (31)P{(1)H} cross
      polarization and magic angle spinning (CP/MAS) NMR spectra contain at least four
      main peaks which appear similar in position and width under all adsorption
      conditions, but vary in intensity with surface loading. The spectral
      characteristics of these peaks, including cross-polarization dynamics and
      chemical shift anisotropy obtained from spinning sideband analysis, suggest that
      they arise from distinct inner-sphere adsorption complexes, most of which are
      protonated. These results indicate that uptake of phosphate by TiO(2) occurs by
      formation of several types of surface complexes.

PMID- 21944060
TI  - The reduction of Ag+ in metallic silver on pseudomelanin films allows for
      antibacterial activity but does not imply unpaired electrons.
AB  - Dopamine-melanin films produced through the oxidation of dopamine in the presence
      of oxygen as an oxidant allow to reduce silver ions onto silver particles as
      already described in the paper by Lee et al. (H. Lee, S.M. Dellatore, W.M.
      Miller, P.B. Messersmith, Science 318 (2007) 426.). This reduction process has to
      occur through the oxidation of moieties present in the melanin film. This
      investigation shows that the free radicals present in the pseudomelanin film,
      quantified by means of electron spin resonance spectroscopy (ESR) for the first
      time, are not used in the transformation of Ag(+) cations to deposit silver. The
      ESR signal is hardly affected by the deposition of silver particles. On the other
      hand, X-ray photoelectron spectroscopy shows a small increase in the density of
      quinone groups and a small decrease of catechol groups on the surface of the film
      during the deposition of silver. This suggests that the deposited pseudomelanin
      films contain a significant fraction of catechol groups able to trigger reduction
      processes of metallic cations. These silver nanoparticles remain adherent to the
      melanin films and allow for a quantitative killing of Escherichia coli over a
      broad range of bacterial dilutions. However, the presence of the bacteria induces
      a release of the nanoparticles. The pseudomelanin films cannot be reused again
      for a silver ion reduction step. Nevertheless, the easy preparation of the
      pseudomelanin-silver composite and its effective one shot bacterial killing
      activity renders the strategy presented in this paper attractive. Some
      fundamental questions about redox process allowed by the pseudomelanin films will
      also be asked.

PMID- 21944061
TI  - Age and fertility: can women wait until their early thirties to try for a first
      birth?
AB  - Postponing the start of childbearing raises the question of fertility postponed
      versus fertility foregone. One of the limitations of previous studies of 'How
      late can you wait?' is that any observed decline in the probability of conception
      with age could be due to a decline in fecundability with age or due to a decline
      in coital frequency with age or due to both factors. Using data from a
      multinational longitudinal study conducted to determine the daily probability of
      conception among healthy subjects, a discrete-time event history model with long
      term survivors (sterile population) is used to study the relationship between age
      and fecundability for childless women, while controlling for the pattern of
      intercourse within a menstrual cycle. The findings suggest that women can wait
      until their early thirties to try for a first birth, providing that they are not
      already sterile, as the magnitude of the decline in fecundability is very modest
      and of little practical importance.

PMID- 21944062
TI  - Different cortical involvement pattern of generalized and localized spasms: a
      magnetoencephalography study.
AB  - We report successful magnetoencephalography (MEG) recording in a child who had
      generalized epileptic spasms (ESs) as well as ESs involving the legs only during
      the recording. MEG source localization results demonstrated that (1) the
      interictal epileptiform discharges and both types of ESs had the same origin,
      that is, the right parietal region, and (2) the two types of ESs had different
      cortical spread patterns, that is, epileptic involvement localized to the right
      parietal region in spasms of the legs and rapid diffuse involvement in
      generalized spasms. In this case, MEG provided new insight into the mechanisms
      underlying the two types of ESs: both types were generated from the same focus,
      and in generalized ESs, abnormal excitation spread to cortical areas diffusely.

PMID- 21944063
TI  - Adipose triglyceride lipase expression and fasting regulation are differently
      affected by cold exposure in adipose tissues of lean and obese Zucker rats.
AB  - Adipose triglyceride lipase (ATGL) hydrolyzes triacylglycerols to diacylglycerols
      in the first step of lipolysis, providing substrates for hormone-sensitive lipase
      (HSL). Here we studied whether ATGL messenger RNA (mRNA) and protein levels were
      affected by 24-h cold exposure in different white adipose tissue depots and in
      interscapular brown adipose tissue of lean and obese Zucker rats submitted to
      feeding and 14-h fasting conditions. HSL mRNA expression was also studied in
      selected depots. In both lean and obese rats, as a general trend, cold exposure
      increased ATGL mRNA and protein levels in the different adipose depots, except in
      the brown adipose tissue of lean animals, where a decrease was observed. In lean
      rats, cold exposure strongly improved fasting up-regulation of ATGL expression in
      all the adipose depots. Moreover, in response to fasting, in cold-exposed lean
      rats, there was a stronger positive correlation between circulating nonesterified
      fatty acids (NEFA) and ATGL mRNA levels in the adipose depots and a higher
      percentage increase of circulating NEFA in comparison with control animals not
      exposed to cold. In obese rats, fasting-induced up-regulation of ATGL was
      impaired and was not improved by cold. The effects of obesity and cold exposure
      on HSL mRNA expression were similar to those observed for ATGL, suggesting common
      regulatory mechanisms for both proteins. Thus, cold exposure increases ATGL
      expression and improves its fasting-up-regulation in adipose tissue of lean rats.
      In obese rats, cold exposure also increases ATGL expression but fails to improve
      its regulation by fasting, which could contribute to the increased difficulty for
      mobilizing lipids in these animals.

PMID- 21944064
TI  - Letter to the editor.

PMID- 21944065
TI  - Diagnostic accuracy of history and physical examination of superior labrum
      anterior- posterior lesions.
AB  - CONTEXT: Type I superior labrum anterior-posterior (SLAP) lesions involve
      degenerative fraying and probably are not the cause of shoulder pain. Type II to
      IV SLAP lesions are tears of the labrum. OBJECTIVE: To determine the diagnostic
      accuracy of patient  history and the active compression, anterior slide, and
      crank tests for type I and type II to IV SLAP lesions. DESIGN: Cohort study.
      SETTING: Clinic. PATIENTS OR OTHER PARTICIPANTS: Fifty-five patients (47 men, 8
      women; age = 40.6 +/-  15.1 years) presenting with shoulder pain.
      INTERVENTION(S): For each patient, an orthopaedic surgeon conducted a clinical
      examination of history of trauma; sudden onset of symptoms; history of popping,
      clicking, or catching; age; and active compression, crank, and anterior  slide
      tests. The reference standard was the intraoperative diagnosis. The operating
      surgeon was blinded to the results of the clinical examination. MAIN OUTCOME
      MEASURE(S): Diagnostic utility was calculated using the receiver operating
      characteristic curve and area under  the curve (AUC), sensitivity, specificity,
      positive likelihood ratio (+LR), and negative likelihood ratio (-LR). Forward
      stepwise binary regression was used to determine a combination of tests for
      diagnosis. RESULTS: No history item or physical examination test had  diagnostic
      accuracy for type I SLAP lesions (n = 13). The anterior slide test had utility
      (AUC = 0.70, +LR = 2.25, -LR = 0.44) to confirm and exclude type II to IV SLAP
      lesions (n = 10). The combination of a history of popping, clicking, or catching
      and the anterior slide test demonstrated  diagnostic utility for confirming type
      II to IV SLAP lesions (+LR = 6.00). CONCLUSIONS: The anterior slide test had
      limited diagnostic utility for confirming and excluding type II to IV SLAP
      lesions; diagnostic values indicated only small shifts in probability. However,
      the  combination of the anterior slide test with a history of popping, clicking,
      or catching had moderate diagnostic utility for confirming type II to IV SLAP
      lesions. No single item or combination of history items and physical examination
      tests had diagnostic utility for type I SLAP lesions.

PMID- 21944066
TI  - Shoulder external rotation fatigue and scapular muscle activation and kinematics
      in overhead athletes.
AB  - CONTEXT: Glenohumeral external rotation (GH ER) muscle fatigue might contribute
      to shoulder injuries in overhead athletes. Few researchers have examined the
      effect of such fatigue on scapular kinematics and muscle activation during a
      functional movement pattern. OBJECTIVE: To examine the effects of GH ER muscle
      fatigue on upper trapezius, lower trapezius, serratus anterior, and infraspinatus
      muscle activation and to examine scapular kinematics during a diagonal movement
      task in overhead athletes. SETTING: Human performance research laboratory.
      DESIGN: Descriptive laboratory study. PATIENTS OR OTHER PARTICIPANTS: Our study
      included 25 overhead athletes (15 men, 10 women; age = 20 +/- 2 years, height =
      180 +/- 11 cm, mass = 80 +/- 11 kg) without a history of shoulder pain on the
      dominant side. INTERVENTION(S): We tested the healthy, dominant shoulder through
      a diagonal movement task before and after a fatiguing exercise involving low
      resistance, high-repetition, prone GH ER from 0 degrees  to 75 degrees  with the
      shoulder in 90 degrees  of abduction. MAIN OUTCOME MEASURE(S): Surface
      electromyography was used to measure muscle activity for the upper trapezius,
      lower trapezius, serratus anterior, and infraspinatus. An electromyographic
      motion analysis system was used to assess 3-dimensional scapular kinematics.
      Repeated-measures analyses of variance (phase * condition) were used to test for
      differences. RESULTS: We found a decrease in ascending-phase and descending-phase
      lower trapezius activity (F(1,25) = 5.098, P = .03) and an increase in descending
      phase infraspinatus activity (F(1,25) = 5.534, P = .03) after the fatigue
      protocol. We also found an increase in scapular upward rotation (F(1,24) = 3.7, P
      = .04) postfatigue. CONCLUSIONS: The GH ER muscle fatigue protocol used in this
      study caused decreased lower trapezius and increased infraspinatus activation
      concurrent with increased scapular upward rotation range of motion during the
      functional task. This highlights the interdependence of scapular and glenohumeral
      force couples. Fatigue-induced alterations in the lower trapezius might
      predispose the infraspinatus to injury through chronically increased activation.

PMID- 21944067
TI  - Custom-molded foot-orthosis intervention and multisegment medial foot kinematics
      during walking.
AB  - CONTEXT: Foot-orthosis (FO) intervention to prevent and treat numerous lower
      extremity injuries is widely accepted clinically. However, the results of
      quantitative gait analyses have been equivocal. The foot models used,
      participants receiving intervention, and orthoses  used might contribute to the
      variability. OBJECTIVE: To investigate the effect of a custom-molded FO
      intervention on multisegment medial foot kinematics during walking in
      participants with low-mobile foot posture. DESIGN: Crossover study. SETTING:
      University biomechanics and ergonomics laboratory. PATIENTS OR OTHER
      PARTICIPANTS: Sixteen participants with low-mobile foot posture (7 men, 9 women)
      were assigned randomly to 1 of 2 FO groups. INTERVENTION(S): After a 2-week
      period to break in the FOs,  individuals participated in a gait analysis that
      consisted of 5 successful walking trials (1.3 to 1.4 m/s) during no-FO and FO
      conditions. MAIN OUTCOME MEASURE(S): Three-dimensional displacements during 4
      subphases of stance (loading response, midstance, terminal stance,  preswing)
      were computed for each multisegment foot model articulation. RESULTS: Repeated
      measures analyses of variance (ANOVAs) revealed that rearfoot complex
      dorsiflexion displacement during midstance was greater in the FO than the no-FO
      condition (F(1,14)  = 5.24, P = .04, partial eta(2) = 0.27). Terminal stance
      repeated-measures ANOVA results revealed insert-by-insert condition interactions
      for the first metatarsophalangeal joint complex (F(1,14) = 7.87, P = .01, partial
      eta(2) = 0.36). However,  additional follow-up analysis did not reveal
      differences between the no-FO and FO conditions for the balanced traditional
      orthosis (F(1,14) = 4.32, P = .08, partial eta(2) = 0.38) or full-contact
      orthosis (F(1,14) = 4.10, P = .08, partial  eta(2) = 0.37). CONCLUSIONS: Greater
      rearfoot complex dorsiflexion during midstance associated with FO intervention
      may represent improved foot kinematics in people with low-mobile foot postures.
      Furthermore, FO intervention might partially correct dysfunctional  kinematic
      patterns associated with low-mobile foot postures.

PMID- 21944068
TI  - Stability of measurement outcomes for voluntary task performance in participants
      with chronic ankle instability and healthy participants.
AB  - CONTEXT: Acceptable measurement stability during data collection is critically
      important to research. To interpret differences in measurement outcomes among
      participants or changes within participants after an intervention program, we
      need to know whether the measurement is stable and consistent. OBJECTIVE: To
      determine the within-session stability of muscle activation patterns for a
      voluntary postural-control task in a group of noninjured participants and a group
      of participants with chronic ankle instability (CAI). DESIGN: Descriptive
      laboratory study. SETTING: Musculoskeletal laboratory. PATIENTS OR OTHER
      PARTICIPANTS: Twenty control participants (8 men, 12 women; age = 21.8 +/- 2.4
      years, height = 164.3 +/- 13.4 cm, mass = 68.4 +/- 17.9 kg) and 20 participants
      with CAI (12 men, 8 women; age = 21.2 +/- 2.1 years, height = 176 +/- 10.2 cm,
      mass = 71.7 +/- 11.3 kg). INTERVENTION(S): Participants performed 4 barefoot
      standing trials, each of which included a 30-second double-legged stance followed
      by a 30-second single-legged stance in 3 conditions: with vision, without vision,
      and with vision on a balance pad. MAIN OUTCOME MEASURE(S): The activity of 7
      muscles of the lower limb was measured for the stance task in the 3 different
      conditions for each trial. The onset of muscle activity and muscle recruitment
      order were determined and compared between the first and the fourth trials for
      both groups and for each condition. RESULTS: We found no differences in the onset
      of muscle activity among trials for both groups or for each condition. The
      measurement error was 0.9 seconds at maximum for the control group and 0.12
      seconds for the CAI group. In the control group, 70% to 80% of the participants
      used the same muscle recruitment order in both trials. In the CAI group, 75% to
      90% used the same recruitment order. CONCLUSIONS: Within 1 session, measurement
      stability for this task was acceptable for use in further research. Furthermore,
      no differences were found in measurement stability across conditions in the
      control or CAI groups.

PMID- 21944069
TI  - Structure, sex, and strength and knee and hip kinematics during landing.
AB  - CONTEXT: Researchers have observed that medial knee collapse is a mechanism of
      knee injury. Lower extremity alignment, sex, and strength have been cited as
      contributing to landing mechanics. OBJECTIVE: To determine the relationship among
      measurements of asymmetry of unilateral hip rotation (AUHR); mobility of the
      foot, which we described as relative arch deformity (RAD); hip abduction-external
      rotation strength; sex; and medial collapse of the knee during a single-leg jump
      landing. We hypothesized that AUHR and RAD would be positively correlated with
      movements often associated with medial collapse of the knee, including hip
      adduction and internal rotation excursions and knee abduction and rotation
      excursions. DESIGN: Descriptive laboratory study. SETTING: Research laboratory.
      PATIENTS OR OTHER PARTICIPANTS: Thirty women and 15 men (age = 21 +/- 2 years,
      height = 171.7 +/- 9.5 cm, mass = 68.4 +/- 9.5 kg) who had no history of surgery
      or recent injury and who participated in regular physical activity volunteered.
      INTERVENTION(S): Participants performed 3 double-leg forward jumps with a single
      leg landing. Three-dimensional kinematic data were sampled at 100 Hz using an
      electromagnetic tracking system. We evaluated AUHR and RAD on the preferred leg
      and evaluated isometric peak hip abductor-external rotation torque. We assessed
      AUHR by calculating the difference between internal and external hip rotation in
      the prone position (AUHR = internal rotation - external rotation). We evaluated
      RAD using the Arch Height Index Measurement System. Correlations and linear
      regression analyses were used to assess relationships among AUHR, RAD, sex, peak
      hip abduction-external rotation torque, and kinematic variables for 3-dimensional
      motion of the hip and knee. MAIN OUTCOME MEASURE(S): The dependent variables were
      joint angles at contact and joint excursions between contact and peak knee
      flexion. RESULTS: We found that AUHR was correlated with hip adduction excursion
      (R = 0.36, P = .02). Asymmetry of unilateral hip rotation, sex, and peak hip
      abduction-external rotation torque were predictive of knee abduction excursion
      (adjusted R(2) = 0.47, P < .001). Asymmetry of unilateral hip rotation and sex
      were predictive of knee external rotation excursion (adjusted R(2) = 0.23, P =
      .001). The RAD was correlated with hip adduction at contact (R(2) = 0.10, R =
      0.32, P = .04) and knee flexion excursion (R(2) = 0.11, R = -0.34, P = .03).
      CONCLUSIONS: Asymmetry of unilateral hip rotation, sex, and hip strength were
      associated with kinematic components of medial knee collapse.

PMID- 21944070
TI  - Comparison of recovery strategies on maximal force-generating capacity and
      electromyographic activity level of the knee extensor muscles.
AB  - CONTEXT: With regard to intermittent training exercise, the effects of the mode
      of recovery on subsequent performance are equivocal. OBJECTIVE: To compare the
      effects of 3 types of recovery intervention on peak torque (PT) and
      electromyographic (EMG) activity of the knee extensor muscles after fatiguing
      isokinetic intermittent concentric exercise. DESIGN: Crossover study. SETTING:
      Research laboratory. PATIENTS OR OTHER PARTICIPANTS: Eight elite judo players
      (age = 18.4 +/- 1.4 years, height = 180 +/- 3 cm, mass = 77.0 +/- 4.2 kg).
      INTERVENTION(S): Participants completed 3 randomized sessions within 7 days. Each
      session consisted of 5 sets of 10 concentric knee extensions at 80% PT at 120
      degrees /s, with 3 minutes of recovery between sets. Recovery interventions were
      passive, active, and electromyostimulation. The PT and maximal EMG activity were
      recorded simultaneously while participants performed isokinetic dynamometer
      trials before and 3 minutes after the resistance exercise. MAIN OUTCOME
      MEASURE(S): The PT and maximal EMG activity from the knee extensors were
      quantified at isokinetic velocities of 60 degrees /s, 120 degrees /s, and 180
      degrees /s, with 5 repetitions at each velocity. RESULTS: The reduction in PT
      observed after electromyostimulation was less than that seen after passive (P <
      .001) or active recovery (P < .001). The reduction in PT was less after passive
      recovery than after active recovery (P < .001). The maximal EMG activity level
      observed after electromyostimulation was higher than that seen after active
      recovery (P < .05). CONCLUSIONS: Electromyostimulation was an effective recovery
      tool in decreasing neuromuscular fatigue after high-intensity, intermittent
      isokinetic concentric exercise for the knee extensor muscles. Also, active
      recovery induced the greatest amount of neuromuscular fatigue.

PMID- 21944071
TI  - Performance of healthy braced participants during aerobic and anaerobic capacity
      tasks.
AB  - CONTEXT: Knee braces were introduced in sports approximately 30 years ago.
      However, the effects of a functional knee brace (FKB) on aerobic and anaerobic
      performance after fatigue are unknown. OBJECTIVE: To investigate whether FKB use
      in noninjured participants hindered performance during aerobic (Leger beep test)
      and anaerobic (repeated high-intensity shuttle test [RHIST]) tasks. DESIGN:
      Crossover study. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: Twenty
      seven healthy male provincial and national basketball and field hockey athletes
      (age = 19.4+/-3.0 years, range, 17-26 years; height = 182.6+/-6.8 cm, range, 168
      196 cm; mass = 80.0+/-9.1 kg, range, 66-108 kg). INTERVENTION(S): Each
      participant was provided a custom-fitted FKB and performed 5 nonbraced (NBR)
      testing sessions over 3 days, followed by 5 braced (BR) testing sessions over 3
      days, for a total of 17.5 hours of testing per condition. During each testing
      session, participants performed 1 trial of the Leger beep test and 1 trial of the
      RHIST in each condition. MAIN OUTCOME MEASURE(S): Predicted maximal oxygen
      consumption (Vo(2) max) and time performance measures were recorded for each NBR
      and BR trial. RESULTS: Initial performance levels were lower for BR than NBR for
      both the Leger beep test (BR = 44.3 mL/kg/min, NBR = 47.3 mL/kg/min; F(1,26) =
      8.726; P = .007) and the RHIST (BR = 16.5 seconds, NBR = 16.2 seconds; F(1,26) =
      13.98, P = .001). However, with continued FKB use, the aerobic performance
      measure remained higher for only the first 2 BR testing sessions (NBR = 46.9
      mL/kg/min, BR = 42.4 mL/kg/min; F(3.0,79.8) = 4.95, P = .003). For the anaerobic
      test, no performance difference was noted between the testing conditions (NBR =
      16.2 seconds, BR = 16.4 seconds; P = .7), whereas fatigue levels were lower
      during BR testing sessions (NBR = 33%, BR = 31%). After 14.0 hours of FKB use,
      performance levels were almost equal between the testing conditions (NBR = 47.6
      mL/kg/min, BR = 46.1 mL/kg/min). CONCLUSIONS: We found an initial decrement in
      performance when the FKB was used during an aerobic or anaerobic task. However,
      after 14.0 hours of FKB use, accommodation to the FKB was possible.

PMID- 21944072
TI  - Comparison of abdominal muscle activity during a single-legged hold in the hook
      lying position on the floor and on a round foam roll.
AB  - CONTEXT: To improve trunk stability or trunk muscle strength, many athletic
      trainers and physiotherapists use various types of unstable equipment for
      training. The round foam roll is one of those unstable pieces of equipment and
      may be useful for improving trunk stability. OBJECTIVE: To assess the effect of
      the supporting surface (floor versus round foam roll) on the activity of
      abdominal muscles during a single-legged hold exercise performed in the hook
      lying position on the floor and on a round foam roll. DESIGN: Crossover study.
      SETTING: University research laboratory. PATIENTS OR OTHER PARTICIPANTS: Nineteen
      healthy volunteers (11 men, 8 women) from a university population.
      INTERVENTION(S): The participants were instructed to perform a single-legged hold
      exercise while in the hook-lying position on the floor (stable surface) and on a
      round foam roll (unstable surface). MAIN OUTCOME MEASURE(S): Surface
      electromyography (EMG) signals were recorded from the bilateral rectus abdominis,
      internal oblique, and external oblique muscles. Dependent variables were examined
      with a paired t test. RESULTS: The EMG activities in all abdominal muscles were
      greater during the single-legged hold exercise performed on the round foam roll
      than on the stable surface. CONCLUSIONS: The single-legged hold exercise in the
      hooklying position on an unstable supporting surface induced greater abdominal
      muscle EMG amplitude than the same exercise performed on a stable supporting
      surface. These results suggest that performing the single-legged hold exercise
      while in the hook-lying position on a round foam roll is useful for activating
      the abdominal muscles.

PMID- 21944073
TI  - Between-seasons test-retest reliability of clinically measured reaction time in
      National Collegiate Athletic Association Division I athletes.
AB  - CONTEXT: Reaction time is typically impaired after concussion. A clinical test of
      reaction time (RT(clin)) that does not require a computer to administer may be a
      valuable tool to assist in concussion diagnosis and management. OBJECTIVE: To
      determine the test-retest reliability of RTclinmeasured over successive seasons
      in competitive collegiate athletes and to compare these results with a
      computerized measure of reaction time (RT(comp)). DESIGN: Case series with
      repeated measures. SETTING: Preparticipation physical examinations for the
      football, women's soccer, and wrestling teams at a single university. PATIENTS OR
      OTHER PARTICIPANTS: 102 National Collegiate Athletic Association Division I
      athletes. INTERVENTION(S): The RT(clin) was measured using a measuring stick
      embedded in a weighted rubber disk that was released and caught as quickly as
      possible. The RT(comp) was measured using the simple reaction time component of
      CogState Sport. MAIN OUTCOME MEASURE(S): Data were collected at 2 time points, 1
      season apart, during preparticipation physical examinations. Outcomes were mean
      simple RT(clin) and RT(comp). RESULTS: The intraclass correlation coefficient
      estimates from season 1 to season 2 were 0.645 for RT(clin) (n = 102, entire
      sample) and 0.512 for RT(comp) (n = 62 athletes who had 2 consecutive valid
      baseline CogState Sport test sessions). CONCLUSIONS: The test-retest reliability
      of RT(clin) over consecutive seasons compared favorably with that of a
      concurrently tested computerized measure of reaction time and with literature
      based estimates of computerized reaction time measures. This finding supports the
      potential use of RT(clin) as part of a multifaceted concussion assessment
      battery. Further prospective study is warranted.

PMID- 21944074
TI  - Certified athletic trainers' knowledge of methicillin-resistant Staphylococcus
      aureus and common disinfectants.
AB  - CONTEXT: Methicillin-resistant Staphylococcus aureus (MRSA) infections are
      increasingly common in athletic settings. The MRSA knowledge and infection
      control practices of certified athletic trainers (ATs) and the cleanliness of the
      athletic training room are important factors in preventing MRSA infections.
      OBJECTIVE: To assess knowledge of MRSA and the use of common disinfectants among
      ATs and to explore their infection-control practices. DESIGN: Cross-sectional
      study. SETTING: High school and collegiate athletic training rooms. PATIENTS OR
      OTHER PARTICIPANTS: A total of 163 ATs from National Collegiate Athletic
      Association Divisions I, II, and III and high schools, representing all 10
      National Athletic Trainers' Association districts. MAIN OUTCOME MEASURE(S):
      Frequencies, analyses of variance, and chi(2) tests were used to assess current
      practices and opinions and relationships between factors. RESULTS: Methicillin
      resistant Staphylococcus aureus was perceived as a national problem by 92% of
      respondents; 57% perceived MRSA as a problem in their practice setting. Most
      respondents had treated general infections (88%), staphylococcal infections
      (75%), and MRSA infections (57%). Male sex was associated with treating all 3
      types of infections (chi(2) test, P < .05). Noncurriculum education was
      associated with a lack of recognition of environmental issues as risk factors and
      with the use of isopropyl alcohol for disinfection (chi(2) test, P < .05). For
      example, 10% of respondents did not recognize that contaminated whirlpools can be
      a source of MRSA infection. Respondents also incorrectly identified effective
      cleaning solutions. Thirty percent of respondents cleaned their hands frequently
      or sometimes before treating each athlete and 35% cleaned their hands sometimes,
      occasionally, or never after seeing each athlete. CONCLUSIONS: The majority of
      ATs were informed about MRSA and made correct disinfection choices. However,
      improvements are still needed, and not all ATs were using proper disinfection
      practices.

PMID- 21944075
TI  - Age, sex, and setting factors and labor force in athletic training.
AB  - CONTEXT: Occupation or occupational setting shifts might be occurring in the
      athletic training profession, and differences between sexes might exist; however,
      little evidence exists to confirm this supposition. OBJECTIVE: To evaluate trends
      in male and female athletic training employment patterns in terms of age and
      occupational setting. DESIGN: Cross-sectional study. SETTING: We requested
      demographic data from the National Athletic Trainers' Association (October 27,
      2009) and obtained frequency totals of members by sex across the occupational
      life span by occupational setting. PATIENTS OR OTHER PARTICIPANTS: Our sample
      included 18 571 athletic trainers employed in the 3 largest classifications of
      occupational settings within the profession: college or university, clinical, and
      secondary school. MAIN OUTCOME MEASURE(S): We calculated frequencies and
      percentages to determine demographic and descriptive data. We analyzed the data
      using an analysis of variance to identify the differences between sexes across
      age and setting. RESULTS: We observed trends in occupational setting and sex
      across ages 22 to 67 years. We identified differences between sexes across the
      ages 22 to 67 years (F(1,18569) = 110818.080, P < .001, eta(2) = .068) and across
      occupational settings (F(1,18569) = 61.908, P < .001, eta(2) = .003), noting a
      marked decline in female athletic trainers in the workforce beginning around age
      28 years and an increase in male athletic trainers in the secondary school
      setting beginning around their middle to late 40s. We observed differences at the
      intercept between setting and sex (F(1,18569) = 63529.344, P < .001, eta(2) =
      .845), which were greater when observed across the ages (F(1,18569) =
      23566787.642, P < .001, eta(2) = .939). CONCLUSIONS: We identified differences
      between sexes across settings and ages in addition to an overall decrease in the
      workforce among all professionals. A marked decline in female athletic trainers
      occurred at age 28 years, yet the male population increased at the secondary
      school level, suggesting a setting shift. Burnout, fatigue, pay scale, and a
      misunderstanding of professional culture and job duties might influence the
      exodus or shift in athletic training.

PMID- 21944076
TI  - Prevalence of eating disorder risk and body image distortion among National
      Collegiate Athletic Association Division I varsity equestrian athletes.
AB  - CONTEXT: Participation in appearance-based sports, particularly at the collegiate
      level, may place additional pressures on female athletes to be thin, which may
      increase the likelihood of their resorting to drastic weight control measures,
      such as disordered eating behaviors. OBJECTIVES: (1) To estimate the prevalence
      and sources of eating disorder risk classification by academic status (freshman,
      sophomore, junior, or senior) and riding discipline (English and Western), (2) to
      examine riding style and academic status variations in body mass index (BMI) and
      silhouette type, and (3) to examine these variations across eating disorder risk
      classification type (eg, body image disturbances). DESIGN: Cross-sectional study.
      SETTING: Seven universities throughout the United States. PATIENTS OR OTHER
      PARTICIPANTS: A total of 138 participants volunteered (mean age = 19.88 +/- 1.29
      years). They represented 2 equestrian disciplines English riding (n = 91) and
      Western riding (n = 47). MAIN OUTCOME MEASURE(S): Participants self-reported
      menstrual cycle history, height, and weight. We screened for eating disorder risk
      behaviors with the Eating Attitudes Test and for body disturbance with sex
      specific BMI silhouettes. RESULTS: Based on the Eating Attitudes Test, estimated
      eating disorder prevalence was 42.0% in the total sample, 38.5% among English
      riders, and 48.9% among Western riders. No BMI or silhouette differences were
      found across academic status or discipline in disordered eating risk. Overall,
      participants perceived their body images as significantly larger than their
      actual physical sizes (self-reported BMI) and wanted to be significantly smaller
      in both normal clothing and competitive uniforms. CONCLUSIONS: Disordered eating
      risk prevalence among equestrian athletes was similar to that reported in other
      aesthetic sports and lower than that in nonaesthetic sports. Athletic trainers
      working with these athletes should be sensitive to these risks and refer athletes
      as needed to clinicians knowledgeable about disordered eating. Professionals
      working with this population should avoid making negative comments about physical
      size and appearance.

PMID- 21944077
TI  - Lateral scapular slide test and scapular mobility in volleyball players.
AB  - CONTEXT: The stability of the scapula in relation to the entire moving upper
      extremity is the key in the throwing sequence. The importance of scapular
      positioning in volleyball players has been well documented in the literature, but
      no one has compared scapular positioning between volleyball players and sedentary
      people. OBJECTIVE: To compare measurements of scapular mobility obtained using
      the lateral scapular slide test between volleyball players and sedentary
      participants without shoulder impairments and to compare changes in scapular
      mobility in players according to the number of years of sport participation.
      DESIGN: Randomized controlled clinical trial. SETTING: University research
      laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 121 people at a single
      university volunteered. Of these, 67 were sedentary (age = 24.3 +/- 2.34 years,
      height = 1.69 +/- 0.09 m, mass = 65.1 +/- 11.91 kg); 54 were volleyball players
      from 4 professional teams and were separated into 2 groups according to their
      years of sport participation. The first group was named young players (n = 31;
      age = 17.7 +/- 2.58 years, height = 1.83 +/- 0.10 m, mass = 68.3 +/- 12.21 kg,
      sport participation <= 9 years), and the second group was named old players (n =
      23; age = 26.9 +/- 3.39 years, height = 1.95 +/- 4.38 m, mass = 90.7 +/- 5.75 kg,
      sport participation >= 10 years). MAIN OUTCOME MEASURE(S): Study participants
      completed a rating scale for pain and a questionnaire about demographic and
      shoulder problems. One assessor performed the lateral scapular slide test and
      additional flexibility measurements around the shoulder girdle. Flexibility
      (external rotation, internal rotation) and scapular position (1, 2, 3) were
      compared among groups (young players, old players, sedentary people) and between
      sides (dominant, nondominant). RESULTS: In sedentary participants, we found
      differences for position 1 (t(66) = 3.327, P = .002), position 2 (t(66) = 2.491,
      P = .004), position 3 (t(66) = 2.512, P = .006), and internal rotation (t(66) =
      2.592, P = .001) between the dominant and nondominant sides. In old players, we
      found differences for position 2 between the dominant and nondominant sides
      (t(22) = 2.956, P = .004). For position 2 (F(2,118) = 4.265, P = .02) and
      position 3 (F(2,118) = 4.702, P = .01), we found differences between young and
      old players. For internal rotation, we found differences between sedentary and
      old players (F(2,118) = 6.578, P = .002) and between young and old players
      (F(2,118) = 3.723, P = .01). CONCLUSIONS: Clinicians evaluating overhead athletes
      need to remember that asymmetric scapular posture between the dominant and
      nondominant sides in unilateral overhead athletes might be normal and not
      necessarily related to injury.

PMID- 21944078
TI  - Risk of hepatitis B and C infections in Tehranian wrestlers.
AB  - CONTEXT: Although bloodborne infections are among the most important global
      health issues, limited data are available on bloodborne infections in athletes.
      OBJECTIVE: To determine and compare the prevalence of markers of hepatitis B
      (HBV) and hepatitis C (HCV) viruses and the risk factors for these infections
      among wrestlers in Tehran and among a control group of athletes in the same
      geographic area who took part in low- to moderate-contact sports (ie, volleyball
      and soccer). DESIGN: Case-control study. SETTING: Laboratory. PATIENTS OR OTHER
      PARTICIPANTS: A total of 420 male wrestlers were randomly selected from 28
      wrestling clubs in Tehran using a cluster-sample-setting method. The control
      group (205 volleyball players from 21 clubs and 205 soccer players from 16 clubs)
      was selected from the same geographic area. MAIN OUTCOME MEASURE(S): The risk
      factors for HBV and HCV and serum levels of anti-HBcAg (antibodies to the HBV
      core antigen), HBsAg (HBV surface antigen), and anti-HCV (antibodies to HCV) in
      both groups. RESULTS: The prevalence of anti-HBcAg was 13.4% (95% confidence
      interval [CI] = 10.2%, 16.7%) in wrestlers and 10.9% (95% CI = 7.9%, 14.0%) in
      the control group. The prevalence of HBsAg was 1.2% (95% CI = 0.2%, 2.2%) in
      wrestlers and 0.5% (95% CI = -0.2%, 1.2%) in the control group. The prevalence of
      anti-HCV was 0.5% (95% CI = -0.2%, 1.1%) in wrestlers and 0 in the control group.
      Some risk factors for bloodborne infections were more common in the wrestlers
      than in the control group. CONCLUSIONS: Within the limits of our study, we found
      no evidence that participation in Tehranian wrestling increased HBV or HCV
      transmission when compared with transmission in athletes participating in low- to
      moderate-contact sports. Prevention of bloodborne infections in Tehranian
      wrestlers should be focused not only on appropriate care for bleeding injuries
      but also on general risk factors for these conditions.

PMID- 21944079
TI  - Osteochondral avulsion fracture of the anterior cruciate ligament femoral origin
      in a 10-year-old child: a case report.
AB  - OBJECTIVE: To describe the case of a 10-year-old football player who sustained a
      comminuted osteochondral avulsion fracture of the femoral origin of the anterior
      cruciate ligament (ACL) via a low-energy mechanism. BACKGROUND: In children, both
      purely cartilaginous and osteochondral avulsion fractures have been described;
      most such ACL avulsions are from the tibial eminence. In the few previous case
      reports describing femoral osteochondral avulsion fractures, high-energy injury
      mechanisms were typically responsible and resulted in a single fracture fragment.
      DIFFERENTIAL DIAGNOSIS: Femoral osteochondral avulsion fracture at the ACL
      origin, femoral cartilaginous avulsion fracture at the ACL origin, midsubstance
      ACL tear, meniscal tear. TREATMENT: Sutures and a button were used to repair the
      comminuted fragments. Postoperatively, a modified ACL reconstruction
      rehabilitation program was instituted. UNIQUENESS: Most injuries of this nature
      in youngsters are caused by a high-energy mechanism of injury, result in an
      osteochondral avulsion fracture of the tibial eminence, and involve a single
      fracture fragment. CONCLUSIONS: Although they occur infrequently, ACL femoral
      avulsion fractures in children can result from a low-energy injury mechanism.
      Identifying the mechanism of injury, performing a thorough physical examination,
      and obtaining appropriate diagnostic studies will enable the correct treatment to
      be implemented, with the goal of safely returning the athlete to play.

PMID- 21944080
TI  - CDC42-positive macrophages may prevent malignant transformation of ovarian
      endometriosis.
AB  - It is currently thought that most clear cell and endometrioid carcinomas arise
      from ovarian endometriosis. We recently suggested that, besides their origin in
      the ovary, reduction of CDC42 messenger RNA (a member of the RHO GTPase family)
      may contribute to explain why clear cell carcinomas are not uncommonly found
      limited to the ovary (stage I). On the other hand, little is known about the
      expression of CDC42 in ovarian endometriosis with and without carcinoma. Twenty
      two endometriotic cysts not associated with carcinoma, 19 endometriotic cysts
      associated with carcinoma (contiguous endometriosis), as well as the 19
      corresponding tumors (11 clear cell, 4 endometrioid, and 4 mixed-clear cell and
      endometrioid-carcinomas) were investigated. We analyzed CDC42 expression both by
      real-time polymerase chain reaction and immunohistochemistry. Endometriotic cysts
      not associated with carcinoma showed higher expression of CDC42 messenger RNA
      than cysts associated with carcinoma (P = .002). Immunohistochemically, CDC42 was
      exclusively expressed by macrophages. CDC42-positive macrophages were present in
      most of the endometriotic cysts not associated with carcinoma (11/19, or 58%). In
      contrast, only 5 endometriotic cysts containing carcinoma (contiguous
      endometriosis) (5/18, or 28%) and 1 ovarian carcinoma arising from endometriosis
      (1/18, or 5%) had CDC42-positive macrophages (58% versus 28%, P = .065; 28%
      versus 5%, P = .046). Our results raise the possibility that CDC42-positive
      macrophages may prevent the development of endometrioid and clear cell
      carcinomas.

PMID- 21944081
TI  - Radical prostatectomy at academic versus nonacademic institutions: a population
      based analysis.
AB  - PURPOSE: Radical prostatectomy outcomes may be better at academic institutions
      than at nonacademic centers. We examined the effect of academic status on 5 short
      term radical prostatectomy outcomes. MATERIALS AND METHODS: In the Health Care
      Utilization Project Nationwide Inpatient Sample we focused on radical
      prostatectomy performed within the 7 most contemporary years (2001 to 2007). We
      tested the rates of homologous blood transfusions and extended length of stay, as
      well as intraoperative and postoperative complications stratified according to
      institutional academic status. Multivariable logistic regression analyses further
      adjusted for confounding variables. RESULTS: Overall 89,965 radical
      prostatectomies were identified, yielding a weighted national estimate of
      442,811. Of those procedures 58.2% were recorded at academic institutions.
      Patients at academic institutions had a lower Charlson comorbidity index and more
      frequently had private insurance (p <0.001). Radical prostatectomy at academic
      institutions was associated with fewer blood transfusions (5.4% vs 7.4%), fewer
      postoperative complications (10.1% vs 12.9%) and lower rates of hospital stay
      above the median (18.0% vs 28.2%). On multivariable analyses institutional
      academic status exerted a protective effect on postoperative complication rates
      (OR 0.93, p = 0.02) and on rates of hospital stay in excess of the median (OR
      0.91, p <0.001). Similarly radical prostatectomy performed at hospitals with a
      high annual caseload were less frequently associated with intraoperative (OR 0.8,
      p = 0.01) and postoperative (OR 0.63, p <0.001) complications, length of stay
      beyond the median (OR 0.19, p <0.001) and homologous blood transfusions (OR 0.35,
      p <0.001). CONCLUSIONS: Even after adjusting for annual hospital caseload,
      radical prostatectomy performed at academic institutions is associated with
      better outcomes than radical prostatectomy performed at nonacademic institutions.
      This relationship illustrates averages and does not imply that academic
      institutions invariably offer better care.

PMID- 21944082
TI  - Changes in cancer volume in serial biopsies of men on active surveillance for
      early stage prostate cancer.
AB  - PURPOSE: We described changes in tumor volume on serial biopsies during an
      extended period in men on active surveillance. MATERIALS AND METHODS: The study
      cohort included men diagnosed with prostate cancer between 1998 and 2010 enrolled
      in active surveillance with 6 or more months of followup. Change in volume over
      time was assessed as change in percent cores positive, percent cancer in 1 biopsy
      core and the doubling of total cancer volume (mm). Logistic regression was used
      to determine the association between grade and volume progression. RESULTS: A
      total of 399 men met the study inclusion criteria. Mean patient age was 61.8
      years old and 313 (78%) had low risk disease. Overall 231 (58%) men had stable
      disease on repeat biopsies. There were 39 (10%) men with a volume increase,
      defined by an increase to more than 33% cores involved or an increase in maximum
      single core positive to more than 50%, and there were 44 (11%) with an increase
      in volume and grade. Approximately 10% of men experienced a decrease in cancer
      volume. On multivariate analysis there was a significant association between
      grade and volume progression on any biopsy (OR 3.07), and a doubling of tumor
      length (mm) at 5 years (OR 6.30). CONCLUSIONS: Prostate cancer volume increases
      and decreases at a similar rate of 10% per biopsy. An increase in tumor volume is
      associated with an increase in cancer grade on early repeat biopsies. However,
      there is a large degree of variation in cancer volume over time.

PMID- 21944083
TI  - Gonadotropin-releasing hormone blockers and cardiovascular disease risk: analysis
      of prospective clinical trials of degarelix.
AB  - PURPOSE: We investigated associations of baseline cardiovascular disease risk
      profile, dosing regimen and treatment duration with incident cardiovascular
      disease events during androgen deprivation therapy with degarelix in patients
      with prostate cancer. MATERIALS AND METHODS: Data on 1,704 men who participated
      in a total of 9 clinical trials were pooled for analysis. Patients received
      treatment with 1-month (20 to 240 mg) or 3-month (240 to 480 mg) doses of
      degarelix for an average of 22 months. End points were ischemic heart disease,
      cerebrovascular disorders, arterial thrombotic/embolic events and intermittent
      claudication. RESULTS: First time cardiovascular disease events were reported in
      92 men in the year before study entry and in 168 after degarelix treatment. Event
      rates were similar before and after degarelix treatment in the total population
      (5.5 vs 6.1/100 person-years, p = 0.45) and in men without cardiovascular disease
      (5.6 vs 4.3/100 person-years, p = 0.11). In contrast, event rates appeared higher
      after degarelix treatment in men with cardiovascular disease at baseline (5.3 to
      10.5 events per 100 person-years, p = 0.0013). On multivariate analysis
      cardiovascular disease at baseline was the strongest independent predictor of
      events, followed by older age, alcohol abstinence and obesity (each p <0.05).
      Degarelix dose and schedule were not independently associated with cardiovascular
      disease events. CONCLUSIONS: In men with prostate cancer observed rates of
      cardiovascular disease events were similar before and after degarelix treatment.
      Events were largely confined to men with preexisting cardiovascular disease and
      further modulated by age and modifiable risk factors. Randomized, controlled
      trials and longer followup are key to fully clarify the comparative safety of
      gonadotropin-releasing hormone antagonists vs agonists.

PMID- 21944084
TI  - The role of self-efficacy in quality of life for disadvantaged men with prostate
      cancer.
AB  - PURPOSE: Self-efficacy is associated with increased participation in treatment
      decision making and improved health related quality of life. We examined the
      influence of perceived efficacy in patient-physician interactions on health
      related quality of life among low income, uninsured men with prostate cancer
      during a 2-year period. MATERIALS AND METHODS: We analyzed data derived on
      participants enrolled in a state funded program providing free prostate cancer
      treatment and care to indigent men. We used validated instruments to measure
      patient self-efficacy (confidence in interacting with physicians), and the
      general and prostate specific health related quality of life outcomes of urinary,
      sexual and bowel bother, symptom distress, psychological well-being and vitality.
      We performed repeated measures analysis with general linear mixed modeling to
      estimate the association of sociodemographic and clinical covariates with health
      related quality of life. RESULTS: Our cohort included a total of 472 observations
      in 99 men. Self-efficacy had a measurable effect on subjective measurements of
      general and disease specific health related quality of life. Men with the lowest
      self-efficacy had inferior mean health related quality of life scores across all
      outcomes. Low self-efficacy was significantly associated with worse bowel bother
      and general symptom distress during the 2-year study period. Similar health
      related quality of life outcomes trajectories were observed across self-efficacy
      categories. CONCLUSIONS: Of disadvantaged men with clinically localized prostate
      cancer those with the lowest self-efficacy in physician interactions fared worst
      across all measured domains of health related quality of life. Interventions to
      improve patient-physician communication in this population may provide physicians
      with a supplemental method by which to address health perceptions, mitigate
      symptom experience and improve health outcomes.

PMID- 21944085
TI  - The results of ureteral stenting after ureteroscopic lithotripsy for ureteral
      calculi: a systematic review and meta-analysis.
AB  - PURPOSE: We evaluated the necessity and adverse effects of routine ureteral stent
      placement after ureteroscopic lithotripsy for ureteral stones. MATERIALS AND
      METHODS: A systematic search of PubMed(r), Embase(r) and the Cochrane Library was
      performed to identify all randomized controlled trials. All relevant studies were
      on the outcomes and complications of ureteroscopic lithotripsy in the management
      of ureteral stones with or without a Double-J stent. The outcomes and
      complications included stone-free rate, operative time, lower urinary tract
      symptoms, hematuria, fever, urinary tract infection, pain and analgesia,
      unplanned medical visits and late postoperative complications. The Cochrane
      Collaboration Review Manager software (RevMan 5.0.2) was used for statistical
      analysis. RESULTS: A total of 16 randomized controlled trials were enrolled for
      analysis and involved 1,573 patients. Of these patients 797 were in the
      nonstented group and 776 in the stented group. There was a statistically
      significant difference in mean operative time between the 2 groups. The incidence
      of lower urinary tract symptoms and pain was significantly higher in the stented
      group than in the nonstented group. Significant differences between the groups
      were not found in fever, urinary tract infection, need for analgesia, unplanned
      readmission and late postoperative complications. CONCLUSIONS: This systematic
      review reveals the obvious disadvantages of ureteral stents after ureteroscopic
      lithotripsy in lower urinary tract symptoms and pain. Stents do not improve stone
      free rate, fever, incidence of urinary tract infection, unplanned medical visits,
      requirement for analgesia and late postoperative complications. Ureteral stenting
      after uncomplicated ureteroscopic lithotripsy could be unnecessary.

PMID- 21944086
TI  - Editorial comment.

PMID- 21944087
TI  - Editorial comment.

PMID- 21944088
TI  - Detection of asymptomatic recurrence during routine oncological followup after
      radical cystectomy is associated with improved patient survival.
AB  - PURPOSE: Whether routine surveillance to detect tumor recurrence after radical
      cystectomy improves patient survival remains in debate. We determined the impact
      on all cause mortality of symptoms at recurrence after cystectomy. MATERIALS AND
      METHODS: We identified 1,599 patients who underwent radical cystectomy for
      urothelial carcinoma at our institution between 1980 and 2000. Median
      postoperative followup was 9.8 years (range 0 to 30.3). Overall survival in
      patients with recurrence stratified by the mode of diagnosis (asymptomatic vs
      symptomatic) was estimated using the Kaplan-Meier method and compared with the
      log rank test. Cox proportional hazard regression models were used to evaluate
      the impact of the mode of diagnosing recurrence on survival. RESULTS: A total of
      606 patients (38%) experienced recurrence after surgery, of whom 137 (23%) were
      asymptomatic and 469 (77%) were symptomatic. Recurrence sites included
      abdomen/pelvis in 450 patients, bone in 185, thorax in 176, urothelium in 154 and
      brain in 39. The most common symptoms at recurrence were pain in 75.3% of
      patients, constitutional symptoms in 57.4% and hematuria in 12.4%. Five and 10
      year overall survival in patients with symptomatic vs asymptomatic recurrence was
      22% and 10% vs 46% and 26%, respectively (p <0.0001). On multivariate analysis
      patients who were symptomatic at recurrence were at almost 60% increased risk for
      death than those who were asymptomatic (HR 1.59, p = 0.0001). CONCLUSIONS:
      Detecting asymptomatic recurrence after cystectomy was associated with
      significantly improved patient survival. Continued investigation to establish the
      optimal followup regimen remains necessary, balancing the benefit of early
      detection with the increased cost of routine surveillance.

PMID- 21944089
TI  - Multiparametric 3T prostate magnetic resonance imaging to detect cancer:
      histopathological correlation using prostatectomy specimens processed in
      customized magnetic resonance imaging based molds.
AB  - PURPOSE: We determined the prostate cancer detection rate of multiparametric
      magnetic resonance imaging at 3T. Precise one-to-one histopathological
      correlation with magnetic resonance imaging was possible using prostate magnetic
      resonance imaging based custom printed specimen molds after radical
      prostatectomy. MATERIALS AND METHODS: This institutional review board approved
      prospective study included 45 patients (mean age 60.2 years, range 49 to 75) with
      a mean prostate specific antigen of 6.37 ng/ml (range 2.3 to 23.7) who had biopsy
      proven prostate cancer (mean Gleason score of 6.7, range 6 to 9). Before
      prostatectomy all patients underwent prostate magnetic resonance imaging using
      endorectal and surface coils on a 3T scanner, which included triplane T2-weighted
      magnetic resonance imaging, apparent diffusion coefficient maps of diffusion
      weighted magnetic resonance imaging, dynamic contrast enhanced magnetic resonance
      imaging and spectroscopy. The prostate specimen was whole mount sectioned in a
      customized mold, allowing geometric alignment to magnetic resonance imaging.
      Tumors were mapped on magnetic resonance imaging and histopathology. Sensitivity,
      specificity, positive predictive value and negative predictive value of magnetic
      resonance imaging for cancer detection were calculated. In addition, the effects
      of tumor size and Gleason score on the sensitivity of multiparametric magnetic
      resonance imaging were evaluated. RESULTS: The positive predictive value of
      multiparametric magnetic resonance imaging to detect prostate cancer was 98%, 98%
      and 100% in the overall prostate, peripheral zone and central gland,
      respectively. The sensitivity of magnetic resonance imaging sequences was higher
      for tumors larger than 5 mm in diameter as well as for those with higher Gleason
      scores (greater than 7, p <0.05). CONCLUSIONS: Prostate magnetic resonance
      imaging at 3T allows for the detection of prostate cancer. A multiparametric
      approach increases the predictive power of magnetic resonance imaging for
      diagnosis. In this study accurate correlation between multiparametric magnetic
      resonance imaging and histopathology was obtained by the patient specific,
      magnetic resonance imaging based mold technique.

PMID- 21944090
TI  - The volume of retractile testes.
AB  - PURPOSE: We used ultrasound to determine the volume of retractile testes in boys
      and compared these volumes with normative testicular volume values. MATERIALS AND
      METHODS: A total of 171 boys were enrolled in the study, of whom 14 were excluded
      from analysis. The 157 boys included (age 0.8 to 11.5 years) were recruited from
      2 different populations. The first subgroup comprised 92 boys previously excluded
      from a study aimed at obtaining normative values of ultrasonographically scanned
      testes. The second group included 65 boys who had been referred to our outpatient
      clinic for nonscrotal testis and who were diagnosed with retractile testis.
      Testicular volume was measured by ultrasound in a scrotal position or in an
      inguinal position. Three separate transverse and longitudinal images of each
      testis were recorded. Length, width and height were measured, and the volume was
      calculated with the formula for an ellipsoid, pi/6 * length * width * height. The
      highest value of the 3 testicular volumes was determined and taken as the volume
      measurement. RESULTS: The volumes measured by ultrasound for the 157 boys with
      276 retractile testes ranged from 0.18 to 1.49 ml (mean 0.50). The volumes of the
      retractile testes were significantly smaller than normative values (p <0.001).
      Furthermore, the testicular volumes of retractile testes measured in an inguinal
      position were significantly smaller than those measured in a scrotal position (p
      <0.001). CONCLUSIONS: The volumes of retractile testes are significantly smaller
      than recently determined normative values.

PMID- 21944092
TI  - Improved prediction of long-term, other cause mortality in men with prostate
      cancer.
AB  - PURPOSE: Comorbidity assessment is essential to triage of care for men with
      prostate cancer. We identified long-term risks of other cause mortality
      associated with comorbidities in the Charlson index and applied these to the
      creation of a prostate cancer specific comorbidity index. MATERIALS AND METHODS:
      We sampled 1,598 cases of prostate cancer diagnosed in 1997 to 2004 at the
      Greater Los Angeles and Long Beach Veterans Affairs Medical Centers. We used Cox
      proportional hazards modeling to determine the risks of other cause mortality
      associated with comorbidities and used these hazard ratios to re-weight the
      Charlson index. We then compared the ability of each index to predict other cause
      mortality. RESULTS: Cox modeling showed that moderate to severe liver disease,
      metastatic solid tumor, lymphoma and leukemia carried the highest risk (HR
      greater than 5) for other cause mortality, followed by moderate to severe chronic
      obstructive pulmonary disease, moderate to severe renal disease, dementia,
      hemiplegia and congestive heart failure (HR 2.5 to less than 3.5). The revised
      and original Charlson indices performed similarly in predicting other cause
      mortality across all patients (c-index 0.816 vs 0.802). However, in survival
      analysis our revised index identified 137 men with a greater than 90% probability
      of other cause mortality within 10 years while the original Charlson identified
      only 51. In multivariate modeling the odds of 5-year other cause mortality for
      men with original Charlson scores 1, 2, 3 and 4+ were 2.9, 6.0, 9.2 and 29.8,
      respectively, compared with 3.9, 6.2, 12.8 and 84.2 for the revised index.
      CONCLUSIONS: Re-weighting the Charlson index allowed for more accurate
      identification of men at highest risk for other cause mortality. Our revised
      index may be used to aid medical decision making for men with prostate cancer.

PMID- 21944091
TI  - Cholelithiasis and the risk of nephrolithiasis.
AB  - PURPOSE: Existing data on the relation between gallstones and kidney stones are
      provocative but limited. Therefore, we determined whether symptomatic
      radiographically confirmed gallstones (and/or cholecystectomy) and symptomatic
      kidney stone disease are independently associated. MATERIALS AND METHODS: We
      conducted cross-sectional and prospective analyses in the Nurses' Health Studies
      I and II (older and younger women, respectively) and the Health Professionals
      Follow-Up Study (men) that included more than 240,000 participants followed for
      14 to 24 years. Regression models adjusted for age, body size, thiazide use, diet
      and other factors. RESULTS: At baseline the multivariate odds ratio of kidney
      stone history in individuals with gallstone history compared to those without was
      1.65 (95% CI 1.46-1.86) in older women, 1.85 (95% CI 1.65-2.07) in younger women
      and 1.61 (95% CI 1.41-1.85) in men. Prospectively, the multivariate relative risk
      of incident kidney stones in participants with gallstone history compared to
      those without was 1.26 (95% CI 1.09-1.44) in older women, 1.32 (95% CI 1.14-1.52)
      in younger women and 1.28 (95% CI 1.03-1.57) in men. The multivariate relative
      risk of incident gallstones in participants with kidney stone history compared to
      those without was 1.17 (95% CI 1.06-1.29) in older women, 1.31 (95% CI 1.19-1.45)
      in younger women and 1.51 (95% CI 1.35-1.68) in men. Prospective lag analyses
      instituting a delay of 4 years between the diagnoses of gallstones and kidney
      stones yielded similar results. CONCLUSIONS: Gallstones and kidney stones are
      independently associated. Additional studies are needed to identify shared
      mechanisms underlying both diseases.

PMID- 21944093
TI  - Percutaneous nephrolithotomy in horseshoe kidneys: factors affecting stone-free
      rate.
AB  - PURPOSE: We report a 2-center study of factors affecting the stone-free rate
      after percutaneous nephrolithotomy in horseshoe kidneys. MATERIALS AND METHODS:
      The postoperative stone-free rate after percutaneous nephrolithotomy was
      evaluated in 47 male and 11 female patients with horseshoe kidneys. All data were
      collected prospectively. Patient and procedure related factors predicting the
      stone-free rate were analyzed by univariate and multivariate tests. RESULTS: The
      mean +/- SD stone burden was 7.62 +/- 7.18 cm(2) (range 1 to 45) and the stone
      was larger than 10 cm(2) in 14 patients (24.1%). Complex stones and staghorn
      stones were present in 21 (36.2%) and 19 patients (32.7%), respectively. The
      overall stone-free rate was 65.5%. Complex stones (p = 0.01), stone burden
      greater than 5 cm(2) (p = 0.013), stone burden greater than 10 cm(2) (p = 0.012),
      multiple stones (p = 0.006) and staghorn stones (p <0.001) were related to
      adverse outcomes on univariate analysis. Logistic regression analysis revealed
      that staghorn calculi was the only factor that significantly predicted the stone
      free rate (p = 0.002). A patient with staghorn calculi in the horseshoe kidney
      was 45 times more likely to have a lower stone-free rate after percutaneous
      nephrolithotomy than a patient without staghorn calculi in the horseshoe kidney.
      CONCLUSIONS: Stone parameters are important when treating calculi in horseshoe
      kidneys. Staghorn calculi are associated with a lower stone-free rate after
      percutaneous nephrolithotomy.

PMID- 21944094
TI  - Increased risk of diabetes in patients with urinary calculi: a 5-year followup
      study.
AB  - PURPOSE: No prospective followup study to date to our knowledge has evaluated the
      relationship between stone disease and the subsequent risk of diabetes mellitus.
      In this population based study we examine the relationship between a history of
      urinary calculi and the risk of diabetes mellitus in Taiwan. MATERIALS AND
      METHODS: A total of 23,569 adult patients with new diagnoses of urinary calculi
      from 2001 to 2003 were recruited together with 70,707 matched enrollees as a
      comparison cohort. All patients were tracked for a 5-year period from the index
      health care encounter to identify those who had a subsequent diagnosis of
      diabetes mellitus. Cox proportional hazards models were used to compute the risk
      of diabetes mellitus for the study and comparison cohorts. RESULTS: Of a total of
      94,276 patients 2,921 (12.39%) from the urinary calculi group and 6,171 (8.73%)
      from the comparison group received a subsequent diagnosis of diabetes mellitus
      during the followup period. The stratified Cox proportional analysis showed that,
      after censoring individuals who died during followup, and adjusting for patient
      monthly income, geographic location, urbanization level, hypertension,
      hyperlipidemia and obesity, the hazard of receiving a first diagnosis of diabetes
      during the 5-year followup was 1.32 times greater for patients with urinary
      calculi than for those in the comparison cohort (95% CI 1.26-1.39, p <0.001).
      CONCLUSIONS: Our results suggest that patients who receive a diagnosis of urinary
      calculi are at increased risk for diabetes mellitus at 5-year followup.

PMID- 21944095
TI  - Watchful waiting and quality of life among prostate cancer survivors in the
      Physicians' Health Study.
AB  - PURPOSE: We examined patient reported outcomes among patients with prostate
      cancer treated with watchful waiting in a nationwide cohort. MATERIALS AND
      METHODS: We collected treatment information and patient reported outcomes from
      1,230 patients with prostate cancer diagnosed with T1-T2 prostate cancer in the
      Physicians' Health Study, of whom 125 were initially treated with watchful
      waiting. Cox proportional hazards regression was used to identify predictors of
      treatment initiation among patients on watchful waiting. Logistic regression was
      used to calculate the OR and 95% CI to assess disease targeted quality of life by
      initial treatment or watchful waiting. RESULTS: At a mean 7.3-year followup 41%
      of patients on watchful waiting remained free of treatment while 34% had received
      radiotherapy or brachytherapy, 16% had received primary hormonal therapy and 10%
      had undergone prostatectomy. Younger age, higher clinical stage, higher Gleason
      score and higher prostate specific antigen at diagnosis predicted progression to
      treatment. Watchful waiting compared to immediate treatment was associated with
      less urinary incontinence (3.5% vs 10%) and impotence (68% vs 78%) but more
      common obstructive urinary symptoms (22% vs 13%) on univariate analysis (each p
      <0.05). Incontinence and impotence differences remained significant after
      adjusting for age, comorbidity and time after cancer diagnosis. Quality of life
      outcomes in men who underwent delayed treatment after initially waiting were not
      worse than in men who underwent immediate treatment. CONCLUSIONS: Findings
      suggest quality of life benefits after watchful waiting in select patients with
      early stage prostate cancer compared to men treated immediately after diagnosis.
      Younger age and greater cancer severity at diagnosis predicted progression to
      treatment.

PMID- 21944096
TI  - The safety profile and acceptability of a disposable male circumcision device in
      Kenyan men undergoing voluntary medical male circumcision.
AB  - PURPOSE: We established the safety and effectiveness as well as the acceptability
      of the Alisklamp(r) device for male circumcision among Kenyan men. MATERIALS AND
      METHODS: To qualify for this hospital based, prospective, interventional cohort
      study one needed to be an uncircumcised adult male who was HIV negative with no
      comorbid factors or genitourinary anomalies precluding circumcision. A total of
      58 men were recruited from a population of 90. Outcome measures were the safety
      profile of Alisklamp and its efficiency and acceptability by participants.
      RESULTS: All 58 procedures were completed without device malfunction, hemorrhage
      or undesirable preputial excision. Mean +/- SD procedure time was 2.43 +/- 1.36
      minutes and mean device removal time was 15.8 +/- 7.4 seconds. There were 2
      adverse events, including mild edema and superficial wound infection related to
      poor hygiene in 1 case each. All men resumed routine activity immediately after
      circumcision. Of the 58 participants 25.9% experienced mild nocturnal erectile
      pains that required no medication. During 6-week followup all men were satisfied
      with the procedure, tolerated the device well and would recommend it to a friend.
      CONCLUSIONS: Alisklamp has an excellent safety profile and excellent
      acceptability among men who undergo circumcision using the device. This technique
      is easy to teach and it would prove to be a handy device to scale up the rate of
      male circumcision. Based on these findings the device merits a comparative
      clinical trial.

PMID- 21944097
TI  - A new preoperative nomogram to predict minimal prostate cancer: accuracy and
      error rates compared to other tools to select patients for active surveillance.
AB  - PURPOSE: We designed and fully evaluated the performance of a nomogram to
      identify patients with prostate cancer who may be suitable for active
      surveillance. MATERIALS AND METHODS: We developed a nomogram to predict the
      probability of minimal prostate cancer (total tumor volume less than 0.5 cc,
      organ confined disease and no Gleason pattern 4 or 5) using preoperative data on
      2,525 Australian patients who underwent radical prostatectomy. Accuracy and error
      rates at multiple probability cutoffs were compared with those of contemporary
      Epstein criteria and the Prostate Cancer Research International: Active
      Surveillance trial inclusion criteria when applied to these patients. High risk
      disease was defined as 1 or more adverse characteristics (including positive
      surgical margins, seminal vesicle invasion, extracapsular extension, 50% or
      greater Gleason pattern 4/5 and/or tumor volume 4.0 cc or greater) at radical
      prostatectomy. RESULTS: Minimal cancer was confirmed in 152 men (6.0%) at
      prostatectomy. The bootstrap corrected predictive accuracy of our nomogram was
      93.3% vs 89.1% and 91.0% for Prostate Cancer Research International: Active
      Surveillance and Epstein criteria, respectively. For men with a nomogram derived
      minimal cancer probability of 0% to 4.9%, 5.0% to 19.9%, 20.0% to 34.9%, 35.0% to
      49.9% and 50.0% to 71.0% the rate of high risk disease was 70.8%, 37.8%, 22.4%,
      9.0% and 3.8%, respectively. In contrast, the rate of high risk disease for men
      who met Prostate Cancer Research International: Active Surveillance and Epstein
      criteria were 17.1% and 13.9%, respectively. CONCLUSIONS: A detailed breakdown of
      the expected rates of false-positive results and high risk disease associated
      with the nomogram derived probability of minimal cancer would provide more
      complete information to clinicians and patients on which to base therapeutic
      clinical decisions for presumed early stage prostate cancer.

PMID- 21944098
TI  - Renal autotransplantation and modified pyelovesicostomy for intractable metabolic
      stone disease.
AB  - PURPOSE: Some patients with intractable metabolic stone disease experience
      narcotic dependence, which cannot be managed with standard treatments. We offered
      these patients renal autotransplantation with a modified pyelovesicostomy as an
      alternative solution. MATERIALS AND METHODS: Renal autotransplantation with
      pyelovesicostomy was performed for 15 kidneys in 12 patients (3 bilateral, 2
      solitary), 9 female and 3 male, with a mean age of 33.8 years (range 16 to 55).
      The etiology of metabolic stone disease was calcium oxalate (40%), cystinuria
      (33%), type 1 renal tubular acidosis (14%), calcium oxalate/urate (7%) and
      medullary sponge kidney (7%). Patients reported that lifetime stone events ranged
      from 10 to more than 70, that underwent an average of 3 to 4 surgical
      interventions per year in the previous 2 years and that they were dependent on
      daily oral narcotics for stone related pain. RESULTS: All 15 kidneys were
      successfully autotransplanted with a mean followup of 41.8 months (range 3 to
      74). We used a modified pyelovesicostomy with ureteral strip in 13 and standard
      Boari tube in 2 cases. All patients continued to pass small stone debris per
      urethra with minimal symptoms. Of 12 patients 11 (92%) were weaned off daily
      narcotics. There have been 17 stone episodes in 4 patients (3 cystinuria) for
      which medical intervention and pain medication was required. The number of
      urological procedures/patients before (155/12 [12.9]) and after (8/12 [0.66])
      autotransplantation was dramatically reduced (paired t test p = 0.0001). The
      preoperative mean estimated glomerular filtration rate was 77.2 cc/minute, and
      73.5, 71.9, 79.2 cc/minute at 12, 36 and 60 months, respectively. CONCLUSIONS:
      Renal autotransplantation and pyelovesicostomy offer patients with intractable
      metabolic stone disease the opportunity to improve quality of life and to
      decrease daily narcotic use.

PMID- 21944099
TI  - Holmium laser enucleation of the prostate-if not now, when?

PMID- 21944100
TI  - Annual endoscopy and urine cytology for the surveillance of bladder tumors after
      enterocystoplasty for congenital bladder anomalies.
AB  - PURPOSE: It is currently recommended that patients with congenital bladder
      anomalies managed by enterocystoplasty undergo annual surveillance with urine
      cytology and endoscopy. We reviewed our experience with this protocol and suggest
      modifications based on this experience. MATERIALS AND METHODS: A total of 65
      patients 10 years or more after enterocystoplasty were placed on an annual
      surveillance protocol consisting of interval medical history, renal-bladder
      ultrasound, serum B12, electrolytes, creatinine, urinalysis, urine cytology and
      endoscopy. RESULTS: Of the 65 patients 50 (77%) with enterocystoplasty (ileal in
      40 and colonic in 10) remain on the protocol. Median age at the initiation of
      surveillance was 28 years (range 24 to 40) with a median time from augmentation
      of 15 years (range 12 to 29). During the first 5 years of surveillance 26 of 250
      cytology results (10.5%) were suspicious for cancer. Further evaluation revealed
      no evidence of malignancy. Specificity for cytology was 90% with unknown
      sensitivity. Of 250 surveillance endoscopic evaluations 4 lesions (1.6%) were
      identified and biopsied/removed. Pathological evaluation revealed 1 adenomatous
      polyp, 1 squamous metaplasia and 2 nephrogenic adenomas. Due to the low event
      rate and high cost routine cytology and endoscopy were discontinued after each
      patient completed 5 years of followup and annual evaluations were maintained. No
      tumors developed during the median surveillance interval of 15 years (range 12 to
      20). Currently median patient age is 42 years (range 36 to 59) and median time
      since augmentation is 27 years (range 23 to 40). CONCLUSIONS: Due to the low
      incidence of malignancy, lack of proven benefit and enhanced cost containment we
      recommend that annual surveillance endoscopy and cytology be discontinued.

PMID- 21944101
TI  - Biomarkers for inflammatory renal damage in children with febrile urinary tract
      infection: a potentially new top-down approach.

PMID- 21944102
TI  - Alterations in connective tissue metabolism in stress incontinence and prolapse.
AB  - PURPOSE: We describe current knowledge about collagen/elastin and extracellular
      matrix metabolism in the genitourinary tract with special emphasis on stress
      urinary incontinence. We also explored the influence of genetics and reproductive
      hormones on extracellular matrix metabolism. MATERIALS AND METHODS: We performed
      a MEDLINE(r) search from 1995 to February 2011 using the key words stress urinary
      incontinence, pelvic organ prolapse, extracellular matrix, collagen, elastin,
      matrix metalloproteinase, collagenase, tissue inhibitors of matrix
      metalloproteinase, elastin metabolism, elastase, connective tissue, supportive
      tissue, mechanical stress, biomechanical properties, selective estrogen receptor
      modulators, transforming growth factor-beta and wound healing. RESULTS: The
      literature searched produced data on 4 areas of significance for extracellular
      matrix metabolism in patients with stress urinary incontinence and prolapse,
      including collagen, elastin and transforming growth factor-beta. Data on collagen
      metabolism continue to support the hypothesis of increased turnover involving
      matrix metalloproteinases and serine proteases in pelvic tissues of affected
      individuals. Elastin metabolism studies suggest increased degradation but also
      abnormal elastin fiber synthesis. Epidemiological data indicate a genetic
      predisposition to abnormal extracellular matrix in affected individuals while
      human tissue and animal models reveal differential expression of candidate genes
      involved in structural proteins. Transforming growth factor-beta pathways have
      been documented to be involved in stress urinary incontinence in human tissues
      and animal models. Finally, these extracellular matrix metabolisms are modulated
      by reproductive hormones and selective estrogen receptor modulators. CONCLUSIONS:
      Pelvic tissue from women with stress urinary incontinence and pelvic organ
      prolapse show a genetic predisposition to abnormal extracellular matrix
      remodeling, which is modulated by reproductive hormones, trauma, mechanical
      stress load and aging. This progressive remodeling contributes to stress urinary
      incontinence/pelvic organ prolapse by altering normal tissue architecture and
      mechanical properties.

PMID- 21944103
TI  - Renal function outcomes in patients treated with partial nephrectomy versus
      percutaneous ablation for renal tumors in a solitary kidney.
AB  - PURPOSE: Partial nephrectomy is the recommended management for small renal
      masses. Percutaneous ablation is safe and effective with comparable short-term
      cancer specific survival. Currently to our knowledge data are lacking on the
      impact of thermal ablation on renal function preservation. We examined the impact
      on renal function of partial nephrectomy vs percutaneous ablation in patients
      with a solitary kidney. MATERIALS AND METHODS: We performed a retrospective
      review to identify patients with a solitary kidney who underwent partial
      nephrectomy or percutaneous ablation at Mayo Clinic Rochester between 2003 and
      2009. Preoperative characteristics and 3-month posttreatment renal function were
      compared using the Wilcoxon rank sum, chi-square and Fisher exact tests. RESULTS:
      During the study period 50 patients underwent percutaneous ablation and 62
      underwent partial nephrectomy. At partial nephrectomy no ischemia was used in 30
      cases (48%), a median of 28 minutes of cold ischemia was used in 26 (42%) and a
      median of 18 minutes of warm ischemia was used in 6 (10%). Patients who underwent
      partial nephrectomy were younger (median age 62.5 vs 68.5 years, p = 0.01) and
      harbored larger tumors (median 3.5 vs 2.5 cm, p = 0.005) with higher nephrometry
      scores (median 9 vs 7, p = 0.03). At 3-month posttreatment followup no
      differences were noted between the 2 groups in glomerular filtration rate (p =
      0.91), change in glomerular filtration rate (p = 0.77) or change in chronic
      kidney disease stage (p = 0.87). Similar results were observed when adjusting for
      age, tumor size and nephrometry score on multivariate analysis. CONCLUSIONS: With
      judicious use of ischemia partial nephrectomy, even for more complex tumors, has
      short-term renal function outcomes similar to those of percutaneous ablation.

PMID- 21944104
TI  - Register based study of bladder exstrophy-epispadias complex: prevalence,
      associated anomalies, prenatal diagnosis and survival.
AB  - PURPOSE: We describe the prevalence, associated anomalies, prenatal diagnosis and
      survival of patients with bladder exstrophy-epispadias complex. MATERIALS AND
      METHODS: Data were extracted from the Northern Congenital Abnormality Survey for
      patients delivered during 1985 to 2008. This survey collects data on congenital
      anomalies in fetuses, stillbirths and live-born infants of mothers residing in
      Northern England (Northumberland, North Cumbria, Tyne and Wear Durham, Darlington
      and Teesside). RESULTS: A total of 43 cases were identified from 824,368
      registered births for a total prevalence of 5.22 per 100,000 (95% CI 3.77-7.03).
      Excluding 1 twin with cloacal exstrophy, 42 cases occurred in singleton
      pregnancies. A total of 29 cases (69%) were isolated and 13 (31%) were associated
      with other anomalies, of which 11 (26%) were other structural and 2 (5%) were
      chromosomal. Male-to-female ratio was 2.2:1 for all singleton cases and 1.4:1 for
      isolated cases. Total prevalence of bladder exstrophy-epispadias complex
      singleton cases was 5.10 per 100,000 registered births (95% CI 3.67-6.89) and
      overall live birth prevalence was 4.63 per 100,000 live births (95% CI 3.28
      6.36). Total prevalence of isolated cases of bladder exstrophy-epispadias complex
      was 3.52 per 100,000 births (95% CI 2.36-5.05) and live birth prevalence was 3.29
      per 100,000 (95% CI 2.17-4.79). Accuracy of prenatal diagnosis was low, with 4
      cases (10%) being detected prenatally by routine ultrasound (bladder exstrophy in
      3, cloacal exstrophy in 1). Overall survival of all infants at 1 year was 95%.
      CONCLUSIONS: This population based study demonstrates a prevalence rate similar
      to other studies, a low prenatal diagnosis rate and high survival.

PMID- 21944105
TI  - Contemporary trends in nephrectomy for renal cell carcinoma in the United States:
      results from a population based cohort.
AB  - PURPOSE: Despite benefits in functional renal outcome and the similar oncological
      efficacy of partial nephrectomy for renal cell carcinoma, previous studies show
      marked underuse of partial nephrectomy. We describe national trends in partial
      and radical nephrectomy using a contemporary, population based cohort. MATERIALS
      AND METHODS: Using the 2003 to 2008 Nationwide Inpatient Sample we identified
      188,702 patients treated with partial or radical nephrectomy for renal cell
      carcinoma at a total of 1,755 hospitals. Multivariate logistic regression was
      used to assess the independent associations of patient and hospital
      characteristics with partial nephrectomy. Post-estimations from multivariate
      logistic regression were done to ascertain the annual predicted probability of
      partial nephrectomy by hospital feature. RESULTS: Overall 149,636 (79.3%) and
      39,066 patients (20.7%) underwent radical and partial nephrectomy for renal cell
      carcinoma, respectively. Partial nephrectomy use increased each year from 16.8%
      in 2003 to 25.1% in 2008 (p for trend <0.001). On multivariate analysis patients
      were more likely to undergo partial nephrectomy at teaching (OR 1.31, p <0.001)
      and urban (OR 1.13, p = 0.05) hospitals compared to nonteaching and rural
      hospitals, respectively. Each quartile of higher nephrectomy annual volume was
      associated with higher odds of partial nephrectomy compared to the lowest
      quartile (OR 1.21, p <0.001). Although annual predicted partial nephrectomy use
      increased across all hospitals, differences in annual partial nephrectomy use by
      teaching status, site (urban vs rural) and case volume persisted with time.
      CONCLUSIONS: Although the use of partial nephrectomy for renal cell carcinoma is
      increasing nationally across all hospitals, academic and urban hospitals as well
      as those with higher nephrectomy volume continue to show higher partial
      nephrectomy use for renal cell carcinoma.

PMID- 21944106
TI  - Post-percutaneous nephrolithotomy systemic inflammatory response: a prospective
      analysis of preoperative urine, renal pelvic urine and stone cultures.
AB  - PURPOSE: Prior studies suggest that renal pelvic urine culture is a more accurate
      predictor of urosepsis. We prospectively determined the correlation between
      preoperative bladder urine cultures, intraoperative renal pelvis cultures and
      stone cultures in patients undergoing percutaneous nephrolithotomy. We also
      examined post-procedure risk factors for systemic inflammatory response syndrome.
      MATERIALS AND METHODS: From February 2009 to February 2011 urine samples from the
      bladder and renal pelvis were collected from patients undergoing percutaneous
      nephrolithotomy. Extracted stones were also sent for culture analysis.
      Postoperatively patients were closely monitored for any signs of systemic
      inflammatory response syndrome. The concordance of urine and stone cultures
      across different sites was examined. Regression analysis was done to identify
      clinical variables associated with systemic inflammatory response syndrome.
      RESULTS: A total of 204 percutaneous nephrolithotomies were done in 198 patients,
      of whom 20 (9.8%) had evidence of systemic inflammatory response syndrome
      postoperatively, including 6 (30%) requiring intensive care. The concordance
      among stone, renal pelvic and preoperative cultures was 64% to 75% with the
      highest concordance between renal pelvic urine and stone cultures. In a
      multivariate model multiple access tracts and a stone burden of 10 cm(2) or
      greater were significant predictors of systemic inflammatory response syndrome
      postoperatively. CONCLUSIONS: Even appropriately treated preoperative urinary
      infections may not prevent infected urine at percutaneous nephrolithotomy. Renal
      pelvic urine and stone cultures may be the only way to identify the causative
      organism and direct antimicrobial therapy. We recommend collecting pelvic urine
      and stone cultures to identify the offending organism in patients at risk for
      sepsis, particularly those with a large stone burden requiring multiple access
      tracts.

PMID- 21944107
TI  - Parental preferences in the management of vesicoureteral reflux.
AB  - PURPOSE: Considering that there are few absolute indications for the timing and
      type of surgical correction of vesicoureteral reflux, we objectively measured
      parental choice in how the child's vesicoureteral reflux should be managed.
      MATERIALS AND METHODS: We prospectively identified patients 0 to 18 years old
      with any grade of newly diagnosed vesicoureteral reflux. All races and genders
      were included, and non-English speakers were excluded from analysis. Parents were
      shown a video presented by a professional actor that objectively described
      vesicoureteral reflux and the 3 treatment modalities of antibiotic prophylaxis,
      open ureteral reimplantation and endoscopic treatment. Then they completed a
      questionnaire regarding their preference for initial management, and at
      hypothetical followup points of 18, 36 and 54 months. Consultation followed with
      the pediatric urologist who was blinded to the questionnaire results. RESULTS: A
      total of 86 girls and 15 boys (150 refluxing units) were enrolled in the study.
      Mean patient age was 2.6 years old. Preferences for initial treatment were
      antibiotic prophylaxis in 36, endoscopic surgery in 26, open surgery in 11,
      unsure in 26 and no response in 2. Among those initially selecting antibiotic
      prophylaxis, after 18 months the preference was for endoscopic treatment, but
      after 36 and 54 months preferences trended toward open surgery. After
      consultation with the pediatric urologist 68 parents chose antibiotic
      prophylaxis. CONCLUSIONS: Our data show that antibiotic prophylaxis is preferred
      as the initial therapy for vesicoureteral reflux by 35.6% of parents. However,
      given persistent vesicoureteral reflux, preferences shifted toward surgery. With
      time the preference for open surgery increased and the preference for endoscopic
      surgery decreased.

PMID- 21944108
TI  - Editorial comment.

PMID- 21944109
TI  - Rectal injury during robot-assisted radical prostatectomy: incidence and
      management.
AB  - PURPOSE: Rectal injury during robot-assisted radical prostatectomy is a rare but
      significant complication. Since the Clavien grading classification of
      complications does not include intraoperative injury without further sequelae,
      rectal injury may be underreported in the literature. We present what is to our
      knowledge the largest retrospective review to date of rectal injury and
      subsequent management. MATERIALS AND METHODS: We reviewed the records of 6,650
      patients who underwent robot-assisted radical prostatectomy at a total of 6
      institutions. Patient characteristics, perioperative parameters, pathological
      findings and rectal injury management were tabulated and analyzed for
      intraoperative predictors of outcome and subsequent management. RESULTS: A total
      of 11 rectal injury cases were identified of the 6,650 robot-assisted radical
      prostatectomies for a combined 0.17% incidence of rectal injury. Of rectal
      injuries 72.7% were identified intraoperatively and most did well with primary
      closure. Delayed recognition injury presented as rectourethral fistula without
      septic complications and required delayed fistula repair after primary diversion.
      We found no conclusive association of rectal injury with any patient parameter,
      intraoperative differences, pathological finding or surgeon experience. Posterior
      prostate plane dissection, including seminal vesicle dissection, is the crucial
      stage when rectal injury can occur and be identified. CONCLUSIONS: Our review of
      the records at 6 centers revealed a combined 0.17% incidence of rectal injury.
      This compares favorably to the incidence in modern open and laparoscopic radical
      prostatectomy series. No preoperative, intraoperative or pathological differences
      correlated with injury. Cases in which rectal injury was identified
      intraoperatively required fewer surgical repeat interventions but ultimately each
      group had acceptable long-term urinary and bowel function results.

PMID- 21944110
TI  - Safety, efficacy and health related quality of life of autologous myoblast
      transplantation for treatment of urinary incontinence in children with bladder
      exstrophy-epispadias complex.
AB  - PURPOSE: Children with bladder exstrophy-epispadias complex undergoing
      endourethral autologous myoblast transplantation to treat urinary incontinence
      were evaluated at 4 years of followup regarding the safety, efficacy and
      durability of the procedure, and health related quality of life. MATERIALS AND
      METHODS: Seven boys underwent autologous myoblast transplantation between May and
      December 2006. All patients had persistent urinary incontinence after bladder
      neck reconstruction and bulking agent injection. Patients were followed for 4
      years after autologous myoblast transplantation regarding clinical outcomes and
      cystometric, urodynamic, uroflowmetric and urethrocystoscopic evaluations. Health
      related quality of life was also measured before treatment and at final followup.
      RESULTS: No evidence of urinary obstruction was observed. Five children (71%)
      were completely continent and 2 (29%) were socially dry with complete daytime
      dryness at final followup. Health related quality of life was improved
      significantly. Urodynamic studies revealed a progressive increase in bladder
      capacity (p <0.001). Mean detrusor leak point pressure showed a 27 cm H(2)O
      (158%) increase during 4-year followup. Uroflowmetry parameters of voided volume
      and average maximum flow rate were improved significantly (p <0.001).
      CONCLUSIONS: The 4-year outcomes demonstrate that autologous myoblast
      transplantation for urinary incontinence in children with bladder exstrophy
      epispadias complex is relatively reliable, reproducible, safe and effective with
      minimal morbidity. This novel treatment represents a promising therapeutic
      approach in patients with urinary incontinence. Further randomized trials with
      larger numbers of patients and longer followup are needed.

PMID- 21944111
TI  - Molecular reactions and ultrastructural damage in the chronically ischemic
      bladder.
AB  - PURPOSE: Clinical and basic research data suggest that pelvic ischemia may
      contribute to bladder overactivity. We characterized the molecular and
      ultrastructural reactions of the chronically ischemic bladder. MATERIALS AND
      METHOD: A model of pelvic ischemia was developed by creating
      iliohypogastric/pudendal arterial atherosclerosis in rabbits. At 12 weeks
      conscious urinary frequency was examined, bladder blood flow was recorded and
      cystometrograms were done using general anesthesia. Bladder tissue was processed
      for molecular and ultrastructural analysis using quantitative real-time
      polymerase chain reaction, Western blot and transmission electron microscopy.
      RESULTS: Conscious urinary frequency and the frequency of spontaneous bladder
      contractions significantly increased in animals with pelvic ischemia. Bladder
      ischemia up-regulated the gene and protein expression of hypoxia inducible factor
      1alpha, transforming growth factor-beta and nerve growth factor B. Vascular
      endothelial growth factor gene expression also increased but protein levels were
      unchanged. Transmission electron microscopy of ischemic bladder samples showed
      swollen mitochondria with degraded granules, thickened epithelium, deformed
      muscle fascicles, collagen deposition and impaired microvasculature with
      thickened intima and disrupted endothelial cell junctions. Degenerating axonal
      and Schwann cell profiles, and myelin sheath splitting around axons and Schwann
      cells were evident in ischemic bladders. CONCLUSIONS: Interrupting pelvic blood
      flow resulted in an ischemic overactive bladder and significant increase in
      conscious urinary frequency. Molecular responses involving hypoxia inducible
      factor, transforming growth factor-beta, vascular endothelial growth factor and
      nerve growth factor were associated with mitochondrial injury, fibrosis,
      microvasculature damage and neurodegeneration. Ischemia may have a key role in
      bladder overactivity and lower urinary tract symptoms.

PMID- 21944114
TI  - A world wide standard of care: doing what is best for the patient.

PMID- 21944112
TI  - Induction of caspase mediated apoptosis and down-regulation of nuclear factor
      kappaB and Akt signaling are involved in the synergistic antitumor effect of
      gemcitabine and the histone deacetylase inhibitor trichostatin A in human bladder
      cancer cells.
AB  - PURPOSE: Previously we reported that the histone deacetylase inhibitor
      trichostatin A (Sigma(r)) synergistically potentiates the antitumor effects of
      cisplatin in human bladder cancer cells. In the current study we explored the
      synergistic interaction between trichostatin A and gemcitabine (Novartis Korea,
      Seoul, Korea), the other mainstay chemotherapeutic regimen for advanced bladder
      cancer. MATERIALS AND METHODS: The bladder cancer cell lines HTB5, HTB9, T24,
      J82, UMUC14 and SW1710 (ATCC(r)) were exposed to gemcitabine and/or trichostatin
      A. Synergism between the 2 drugs was determined by the combination index based on
      the Cell Counting Kit-8 assay (Dojindo Molecular Technologies, Rockville,
      Maryland) and by a clonogenic assay. Flow cytometry was used to evaluate cell
      cycle distribution and apoptosis. The expression of cell cycle (p21(WAF1/CIP1),
      cyclin A, B1 and D1, p-CDC2C, CDC2C, p-CDC25C, CDC25C and pRb), apoptosis
      (caspase-3, 8 and 9, PARP, Bcl-2, Bad and Bax), NF-kappaB (NF-kappaB, p
      IkappaBalpha, IkappaBalpha, p-IKKalpha, IKKalpha, cIAP1, cIAP2 and XIAP) and
      survival (p-Akt, Akt, p-mTOR, mTOR and PTEN) related proteins was analyzed by
      Western blot. RESULTS: Isobolic analysis of the Cell Counting Kit-8 assay
      revealed strong synergism between gemcitabine and trichostatin A, which caused a
      4.6 to 25.4-fold gemcitabine dose reduction and a 1.9 to 41.4-fold trichostatin A
      dose reduction while killing an estimated 90% of bladder cancer cells. The
      underlying mechanisms could be synergistic cell cycle arrest, induction of
      caspase mediated apoptosis, and down-regulation of the antiapoptotic NF-kappaB
      and Akt signaling pathways. CONCLUSIONS: Results show that trichostatin A may
      synergistically enhance gemcitabine mediated cell cycle arrest and apoptosis,
      suggesting the potential of using histone deacetylase inhibitors as combination
      agents to enhance the antitumor effect of gemcitabine for advanced bladder
      cancer.

PMID- 21944115
TI  - Open retropubic reanastomosis for highly recurrent and complex bladder neck
      stenosis.
AB  - PURPOSE: We assessed the success rate of open reanastomosis for highly recurrent
      bladder neck stenosis resistant to transurethral treatment. Due to the paucity of
      available data the success rate of this procedure is not well defined, although
      it can be a last treatment option before urinary diversion. MATERIALS AND
      METHODS: A total of 158 patients were treated for bladder neck stenosis in 1998
      to 2007, of whom 20 underwent open reanastomosis for highly recurrent or complex
      bladder neck stenosis after radical prostatectomy and were seen for followup 3
      months postoperatively. They received a standardized questionnaire at the time of
      data acquisition in this retrospective analysis. RESULTS: The 20 patients
      underwent a mean of 3.7 previous surgeries. Median followup was 59.2 months.
      Stenosis recurred after reanastomosis in 8 patients (40%) while the remaining 60%
      were recurrence free. Seven recurrences were successfully treated endoscopically,
      resulting in an overall combined 95% success rate. Urinary diversion was
      performed in 1 patient with another recurrence after reanastomosis and
      transurethral resection. Four patients (31%) had new onset incontinence and 13
      were completely incontinent, of whom 9 were successfully treated with artificial
      urinary sphincter implantation. In another patient artificial urinary sphincter
      implantation is scheduled and 3 elected no further treatment. CONCLUSIONS: Open
      reanastomosis for recurrent bladder neck stenosis is a good therapeutic option in
      cases of endoscopic treatment failure. The initial success rate after
      reanastomosis was 60%, which increased to 95% after secondary treatment. There
      was a relatively high risk of new onset incontinence after reconstructive surgery
      but this was successfully treated with artificial urinary sphincter implantation
      in most patients.

PMID- 21944116
TI  - Cutaneous ureterostomy technique for adults and effects of ureteral stenting: an
      alternative to the ileal conduit.
AB  - PURPOSE: We present surgical modifications that improved the outcome of cutaneous
      ureterostomies. MATERIALS AND METHODS: A total of 310 patients with a median age
      of 71 years (range 38 to 88) underwent cutaneous ureterostomy as urinary
      diversion. Median followup was 25 months (range 1 to 172). The technique included
      1) transposition of the left ureter above the inferior mesenteric artery, 2)
      mobilization of the ileocecal segment with repositioning above each terminal
      ureter, 3) abdominal wall hiatus fixation with 4 angle sutures and 4) YV plasty
      of the ureters with edge-to-edge anastomosis for stomal creation. In the 161
      group 1 patients (59.1%) the Double-J(r) stents were removed in less than 3
      months. Stents remained longer than 3 months in the 111 group 2 patients (40.8%).
      RESULTS: Of the 272 patients ureteral obstruction developed in 36 (13.2%).
      Ureteral obstruction was on the right side in 6 patients (2.2%), on the left side
      in 27 (9.9%) and bilateral in 3 (1.1%). Ureteral obstruction was treated with
      restenting in 20 cases (55.4%), stomal revision in 12 (33.3%) and conversion to a
      conduit in 4 (11%). Ureteral obstruction developed on the right side, on the left
      side and bilaterally in 3.7%, 13.7% and 1.82% of the patients in group 1, and in
      0%, 4.5% and 0%, respectively, of those in group 2. Stenting time impacted only
      the left ureter with less obstruction in the group with longer stent placement
      (greater than 3 months) (p = 0.01). CONCLUSIONS: As with other types of urinary
      diversion, left ureteral obstruction is a common complication of bilateral
      cutaneous ureterostomies. Long-term stenting for greater than 3 months and the
      applied surgical modifications improved the clinical outcome of this type of
      urinary diversion.

PMID- 21944117
TI  - Tissue engineering potential of urothelial cells from diseased bladders.
AB  - PURPOSE: We examined the suitability of urothelium from patients with abnormal
      bladders for use in surgical reconstruction using a tissue engineering approach
      that would require autologous urothelium to be expanded by propagation in cell
      culture. MATERIALS AND METHODS: Resection specimens from 8 children (median age
      9.8 years) with abnormal bladders (neuropathic in 4, posterior urethral valves in
      2, epispadias in 1, nonneurogenic in 1) were collected with informed parental
      consent during planned urological procedures. Six patients had recurrent urinary
      tract infections and 7 underwent frequent intermittent catheterization. A
      representative sample was immunohistologically processed to assess urothelial
      proliferation and differentiation status, and the remaining 7 cases were
      processed for urothelial cell culture. Five normal adult urothelial samples were
      included as controls. RESULTS: Immunohistological assessment indicated that 3 of
      8 samples lacked urothelial differentiation associated expression of UPK3a or
      CK20. Four of 7 samples resulted in successful primary culture, with 1 sample
      lost to underlying infection and 2 not surviving in culture. All 4 cultures grew
      beyond passage 3 before senescence but all showed reduced proliferation capacity
      and a compromised ability to form a barrier urothelium compared to controls.
      CONCLUSIONS: While normal human urothelium is highly regenerative and derived
      cells are highly proliferative in culture, our results with urothelium from
      abnormal pediatric bladders indicate a reduced capacity for proliferation and
      differentiation in vitro. This finding may indicate a need to identify
      alternative cell sources for engineered bladder reconstruction.

PMID- 21944118
TI  - Re: Practice guidelines for imaging studies in children after the first urinary
      tract infection: M. Venhola, N. P. Huttunen, M. Renko, T. Pokka and M. Uhari J
      Urol 2010; 184: 325-328.

PMID- 21944119
TI  - Identification of genomic alterations associated with metastasis and cancer
      specific survival in clear cell renal cell carcinoma.
AB  - PURPOSE: We identified regions of DNA copy number changes that are significantly
      associated with metastasis and clinical outcome in patients with clear cell renal
      cell carcinoma. MATERIALS AND METHODS: We analyzed 53 primary clear cell renal
      cell carcinomas, including 31 metastasized and 22 nonmetastasized tumors, by
      array comparative genomic hybridization with a median resolution of 1 to 1.5 Mbp.
      To validate copy number aberrations with potential prognostic value we performed
      fluorescence in situ hybridization analysis using commercially available
      fluorescent probes. RESULTS: We identified 5 recurrent chromosomal aberrations
      that were significantly associated with metastasis, including gains of 1q21.3,
      12q13.12, 12q13.3q14.1 and 20q11.21q13.2, and loss of 9p21.3p24.1. The most
      prominent of them with the highest OR for metastatic risk were loss of
      9p21.3p24.1, and gains of 1q21.3 and 20q11.21q13.32. Eight alterations involving
      chromosomes 7, 9, 12, 16 and 20 significantly correlated with shortened cancer
      specific survival. The lowest p values on Kaplan-Meier analysis showed losses of
      9p21.3p24.1 and 9q32q33.1, and gains of 7q36.3 and 20q11.21q13.32. Fluorescence
      in situ hybridization done in the same cohort for the 4 select regions 1q21.3,
      7q36.3, 9p21.3p24.1 and 20q11.21q13.32 clearly confirmed the results of array
      comparative genomic hybridization. CONCLUSIONS: Data suggest that specific
      chromosomal alterations in clear cell renal cell carcinoma can be used to predict
      metastasis and cancer specific survival in patients with clear cell renal cell
      carcinoma. It seems possible to design a combined fluorescence in situ
      hybridization assay based on these genetic targets for outcome prediction, which
      can be used for routine diagnostics.

PMID- 21944120
TI  - Pediatric testicular torsion epidemiology using a national database: incidence,
      risk of orchiectomy and possible measures toward improving the quality of care.
AB  - PURPOSE: Testicular torsion causes considerable morbidity in the pediatric
      population but the societal burden is poorly quantified. We determined the modern
      incidence of testicular torsion as well as the current rates of orchiectomy and
      attempted testicular salvage, and identified the risk factors for testicular
      loss. MATERIALS AND METHODS: A cohort analysis was performed of 2,443 boys (age 1
      month to less than 18 years) and 152 newborns who underwent surgery for
      testicular torsion in the 2000, 2003 and 2006 Healthcare Cost and Utilization
      Project Kids' Inpatient Database. Patient and hospital characteristics predictive
      of orchiectomy vs attempted testicular salvage were analyzed. RESULTS: There was
      a bimodal distribution of testicular torsion with peaks in the first year of life
      and in early adolescence. The overall mean age +/- SD at presentation was 10.6 +/
      5.8 years. The estimated yearly incidence of testicular torsion for males
      younger than 18 years old was 3.8 per 100,000. Orchiectomy was performed in 41.9%
      of boys undergoing surgery for torsion. The adjusted odds ratio for orchiectomy
      was highest for children in the youngest age quartile (younger than 10 years old,
      OR 1.58, 95% CI 1.25-2.00). Additional independent predictors of orchiectomy
      included Medicaid insurance (OR 1.39, 95% CI 1.14-1.69), black race (OR 1.33, 95%
      CI 1.04-1.71), nonemergency room admission source (OR 1.97, 95% CI 1.60-2.42) and
      surgery at a children's hospital or unit (OR 1.64, 95% CI 1.36-1.98).
      CONCLUSIONS: Testicular torsion is uncommon but the rate of orchiectomy is high,
      especially in the youngest patients.

PMID- 21944121
TI  - The role of procalcitonin for acute pyelonephritis and subsequent renal scarring
      in infants and young children.
AB  - PURPOSE: We assessed the usefulness of procalcitonin as a biological marker in
      diagnosing acute pyelonephritis and for predicting subsequent renal scarring in
      young children with a first febrile urinary tract infection. MATERIALS AND
      METHODS: Children 2 years old or younger with a first febrile urinary tract
      infection were prospectively studied. Renal parenchymal involvement was assessed
      by (99m)Tc-dimercaptosuccinic acid scan within 5 days of admission and after 6
      months. Serum samples from all patients were tested for procalcitonin, C-reactive
      protein and white blood cell count measurements. RESULTS: The 112 enrolled
      patients (age range 24 days to 24 months old) were divided into acute
      pyelonephritis (76) and lower urinary tract infection (36) groups according to
      the results of (99m)Tc-dimercaptosuccinic acid scans. Median values of
      procalcitonin, C-reactive protein and white blood cell count at hospitalization
      were significantly higher in patients with acute pyelonephritis than in those
      with lower urinary tract infection. The area under receiver operating
      characteristic curves showed that procalcitonin was superior to C-reactive
      protein and white blood cell count as a marker for diagnosing acute
      pyelonephritis. Initial and post-antibiotic treatment procalcitonin values were
      significantly higher in children with renal scarring than in those without
      scarring (p <0.001). Procalcitonin values at hospitalization and after treatment
      were independent predictors of later renal scarring on logistic regression
      analysis. CONCLUSIONS: Our results indicate the superior diagnostic accuracy of
      procalcitonin for predicting acute pyelonephritis in children 2 years old or
      younger. Higher initial and posttreatment procalcitonin values are independent
      risk factors for later renal scarring.

PMID- 21944122
TI  - Safety and efficacy of Eraser laser enucleation of the prostate: preliminary
      report.
AB  - PURPOSE: We ascertained the safety and efficacy of the 1,318 nm diode Eraser
      laser (Rolle and Rolle, Salzburg, Austria) for transurethral enucleation of the
      prostate. This laser has been successfully used to resect lung metastasis. It
      cuts and coagulates vascular rich tissue safely and effectively. We describe a
      prospective, randomized trial of Eraser laser prostate enucleation vs bipolar
      transurethral prostate resection. MATERIALS AND METHODS: A total of 60 patients
      with lower urinary tract symptoms suggesting bladder outlet obstruction and a
      mean prostate size of 59.5 ml on transrectal ultrasound were randomized to Eraser
      laser prostate enucleation or bipolar transurethral prostate resection. Patients
      were assessed preoperatively, and 1 and 6 months postoperatively. RESULTS: Eraser
      laser prostate enucleation was equivalent to bipolar transurethral prostate
      resection in improvement in International Prostate Symptom Score, maximal flow
      rate and quality of life. Laser enucleation was significantly superior to bipolar
      transurethral resection for measured blood loss (mean +/- SD 116.83 +/- 97.02 vs
      409.83 +/- 148.61 ml), catheter time (mean 32.80 +/- 8.74 vs 65.73 +/- 13.72
      hours) and hospital time (mean 45.13 +/- 14.77 vs 91.20 +/- 11.76 hours, each p
      <0.05). Using the validated Clavien-Dindo system there were 3 grade Id and 1
      grade II complications. CONCLUSIONS: Eraser laser prostate enucleation and
      bipolar transurethral prostate resection were equally safe and effective to
      relieve bladder outflow obstruction and lower urinary tract symptoms. This laser
      technique has the advantage of less blood loss, and shorter catheter time and
      hospital stay.

PMID- 21944123
TI  - Predicting prostate biopsy result in men with prostate specific antigen 2.0 to
      10.0 ng/ml using an investigational prostate cancer methylation assay.
AB  - PURPOSE: The inadequacies of prostate specific antigen testing have created a
      need for novel markers for prostate cancer screening. The investigational
      ProCaMTM prostate cancer methylation assay detects aberrant methylation of DNA in
      cells associated with prostate cancer. We describe a large, prospective,
      multicenter study done to verify the performance of this assay. MATERIALS AND
      METHODS: The assay is designed to detect epigenetic modifications in the 3
      markers GSTP1, RARbeta2 and APC, which are indicative of prostate cancer. A total
      of 232 men with cancer and 283 without cancer from 18 clinical sites were
      evaluated by trained operators at central testing laboratories. Study inclusion
      criteria were age 40 to 75 years, total prostate specific antigen between 2.0 and
      10.0 ng/ml, and a digital rectal examination result. All participants signed an
      informed consent form and underwent transrectal ultrasound guided needle biopsy
      with 10 or more cores. RESULTS: Assay sensitivity was 60%, specificity was 80%
      and the informative rate was 97%. Assay predictive accuracy was higher than that
      of age, digital rectal examination, family history, prostate specific antigen,
      prior negative biopsy and prostate volume (AUC 0.73 vs 0.52 to 0.66, p <0.038).
      Risk factors plus the assay improved overall predictive power (AUC 0.79, p =
      0.001). A man with a positive prostate cancer methylation result was 7.7 times
      more likely to have high grade cancer. CONCLUSIONS: The prostate cancer
      methylation assay correlated with positive biopsy and with Gleason score. This
      assay has the potential to add value to the biopsy decision making process by
      improving current prostate cancer screening algorithms to more accurately
      identify men with prostate cancer.

PMID- 21944124
TI  - Soluble gp130 regulates prostate cancer invasion and progression in an
      interleukin-6 dependent and independent manner.
AB  - PURPOSE: Soluble gp130 is a regulator of interleukin-6/soluble interleukin-6
      receptor signaling that influences prostate cancer progression. We determined the
      association of soluble gp130 with prostate cancer prognosis, invasiveness and
      epithelial-to-mesenchymal transition. MATERIALS AND METHODS: A total of 423
      preoperative and 206 postoperative blood samples were available from patients
      treated with radical prostatectomy for clinically localized prostate cancer.
      Prostate cancer cell lines were used for in vitro studies. Plasma soluble gp130,
      interleukin-6 and soluble interleukin-6 receptor levels were measured using
      enzyme immunoassay. In vitro invasion assays and quantification of E-cadherin
      expression were done using modified Boyden chambers and Western blot,
      respectively. RESULTS: In patients treated with radical prostatectomy higher
      preoperative plasma soluble gp130 was significantly associated with higher biopsy
      and pathological Gleason sum, extraprostatic extension, seminal vesicle invasion,
      lymph node metastasis and biochemical recurrence. In a subset of 206 patients
      postoperative soluble gp130 levels were 18% lower than preoperative levels (p =
      0.037). Soluble gp130 levels weakly correlated with preoperative plasma
      interleukin-6 and soluble interleukin-6 receptor levels. In vitro soluble gp130
      alone increased the invasiveness of androgen responsive prostate cancer cells and
      induced a significant decrease in E-cadherin. In patients higher plasma soluble
      gp130 was associated with features of biologically aggressive prostate cancer.
      The decrease in postoperative plasma soluble gp130 after surgery suggests that
      the higher blood levels of soluble gp130 are produced by tumor cells.
      CONCLUSIONS: Data suggest that soluble gp130 has a role in prostate cancer
      invasion in an interleukin-6 dependent and independent manner.

PMID- 21944125
TI  - Once nocturia, always nocturia? Natural history of nocturia in older men based on
      frequency-volume charts: the Krimpen study.
AB  - PURPOSE: Nocturia is a highly prevalent and bothersome symptom that might
      (spontaneously) resolve. However, longitudinal data are not available on the
      incidence and resolution of nocturia assessed with frequency-volume charts. In
      this study we determined the prevalence, incidence and resolution rates of
      nocturia assessed by frequency-volume charts, and compared nocturnal voiding
      frequency over time as assessed by frequency-volume charts and questionnaires.
      MATERIALS AND METHODS: A longitudinal, population based study was conducted among
      1,688 men 50 to 78 years old with followup rounds at 2.1, 4.2 and 6.5 years.
      Nocturnal voiding frequency was determined with frequency-volume charts and, for
      comparison purposes, with a question from the International Prostate Symptom
      Score. Nocturia was defined as nocturnal voiding frequency 2 or greater.
      Prevalence, incidence and resolution rates were also determined. RESULTS: At the
      2.1-year followup the incidence rate was 23.9% and the resolution rate was 36.7%.
      The incidence rate was highest in the oldest group (70 to 78 years) and lowest in
      the youngest (50 to 54 years), whereas the resolution rate was highest in the
      group 55 to 59 years old and lowest in the oldest group. Because of the high
      resolution rate, no reliable incidence rates can be calculated. Despite
      fluctuation, the prevalence of nocturia increased with age and over time (from
      34.4% to 44.7% for the total group, p <0.05). Men who had a frequency-volume
      chart-nocturnal voiding frequency less than International Prostate Symptom Score
      nocturnal voiding frequency (6% of the population) more often had this later on.
      CONCLUSIONS: In this population frequency-volume chart assessed nocturia shows
      considerable fluctuation. Nevertheless, prevalence increases over time and with
      increasing age. Men who once had frequency-volume chart-nocturnal voiding
      frequency less than International Prostate Symptom Score-nocturnal voiding
      frequency are more likely to have this again. Therefore, frequency-volume charts
      as well as the International Prostate Symptom Score should be used when
      evaluating nocturia.

PMID- 21944126
TI  - Renal function change after refluxing type orthotopic ileal substitution.
AB  - PURPOSE: We investigated the impact of the presence and severity of
      vesicoureteral reflux on renal function in patients with an ileal orthotopic
      bladder substitute without an antirefluxing mechanism after radical cystectomy.
      We compared results in patients with an ileal conduit. MATERIALS AND METHODS: In
      101 patients (195 renal units) who underwent radical cystectomy, including 73
      (142 renal units) with an ileal orthotopic substitute and 28 (53 renal units)
      with a conduit between July 2004 and August 2009, we evaluated (99m)technetium
      diethylenetetramine pentaacetic acid renal scans to measure individual glomerular
      filtration rates preoperatively. This was followed annually along with
      postoperative voiding cystourethrography. We analyzed factors influencing a
      change in the postoperative glomerular filtration rate, including reflux presence
      and severity. RESULTS: In patients with an orthotopic substitute vesicoureteral
      reflux was observed in 104 renal units (73.2%). Reflux was bilateral in 80.8% of
      renal units and grade 3 or higher in 45 (31.7%). The mean glomerular filtration
      rate of all renal units remained unchanged perioperatively and was not influenced
      by reflux presence or severity. The percent change in the glomerular filtration
      rate was similar between patients with an orthotopic substitute and an ileal
      conduit. Post-void residual urine was a significant risk factor for febrile
      urinary tract infection and subsequent hydronephrosis in the absence of
      obstruction as well as an independent predictor of a significant glomerular
      filtration rate decrease (p = 0.009). CONCLUSIONS: Vesicoureteral reflux that
      develops in refluxing type urinary diversions does not significantly alter renal
      function regardless of its severity unless it is coupled with post-void residual
      urine. Post-void residual urine carries a significant risk of febrile urinary
      tract infection and it is an independent predictor of renal function
      deterioration.

PMID- 21944127
TI  - Holmium laser enucleation of the prostate: long-term durability of clinical
      outcomes and complication rates during 10 years of followup.
AB  - PURPOSE: We assessed the long-term durability of subjective and objective
      outcomes and complication rates after holmium laser enucleation of the prostate.
      MATERIALS AND METHODS: We conducted a retrospective analysis of 949 evaluable
      patients treated with holmium laser enucleation of the prostate between March
      1998 and September 2010 at a single center. Study variables included
      International Prostate Symptom Score, quality of life, maximum urinary flow rate,
      post-void residual urine volume and prostate specific antigen. RESULTS: Mean
      followup was 62 months. Mean preoperative post-void residual volume, maximal flow
      rate, International Prostate Symptom Score and quality of life were 311 ml, 7.9
      ml per second, 19 and 3.8, respectively. Postoperatively all variables showed
      significant improvement starting at month 1 of followup and remained improved for
      the entire followup period. Patients with acute urinary retention represented 36%
      (343) of the cohort. Postoperative mean post-void residual volume was 45, 25.7
      and 52 ml, mean maximal flow rate was 21.5, 24.3 and 23.4 ml per second, mean
      International Prostate Symptom Score was 7.3, 4.4 and 3.8, and mean quality of
      life was 1.7, 1 and 0.7 at 1 month, 1 year and 10 years, respectively. Persistent
      urge and stress incontinence were found in 1% and 0.5% of patients, respectively.
      Bladder neck contracture, urethral stricture and reoperation due to residual
      adenoma developed in 0.8%, 1.6% and 0.7% of patients. CONCLUSIONS: Holmium laser
      enucleation of the prostate represents an effective treatment modality for men
      with symptomatic benign prostatic hyperplasia with a low rate of complications
      during a long followup. Patients who experience improvement from baseline to
      early followup maintain improvement at later followup.

PMID- 21944128
TI  - Changes in uroflowmetry maximum flow rates after urethral reconstructive surgery
      as a means to predict for stricture recurrence.
AB  - PURPOSE: A reliable, noninvasive screening method for urethral stricture
      recurrence after urethroplasty is needed. We hypothesized that changes in flow
      rates on uroflowmetry relative to preoperative values might help predict
      stricture recurrence. MATERIALS AND METHODS: All men who underwent urethral
      reconstructive surgery from 2000 to 2009 with adequate preoperative and
      postoperative uroflowmetry studies were included in the study. Preoperative and
      postoperative maximum flow rates were compared. The absolute change in maximum
      flow rate was compared between patients with and those without recurrence as
      determined by retrograde urethrogram. RESULTS: A total of 125 patients treated
      with urethroplasty were included in the study. Mean +/- SD preoperative maximum
      flow rate was 11.8 +/- 9.1 ml per second, which did not vary by stricture length
      (p = 0.11), patient age (p = 0.46) or stricture location (p = 0.58). The change
      in maximum flow rate in men without recurrence was 19.2 +/- 11.7 vs 0.2 +/- 6.4
      ml per second (p <0.001) in failed repairs. Setting a change in maximum flow rate
      of less than 10 ml per second as a screen for stricture recurrence would have
      resulted in a test sensitivity and specificity of 92% and 78%, respectively.
      There were 85 men without stricture recurrence who underwent more than 1
      postoperative uroflowmetry study. Repeated maximum flow rate values achieved
      reasonable test reproducibility (r = 0.52), further supporting the use of
      uroflowmetry. CONCLUSIONS: Change in flow rate after urethral reconstruction
      represents a promising metric to screen for stricture recurrence that is
      noninvasive and has a high sensitivity.

PMID- 21944129
TI  - Role of inflammatory related gene expression in clear cell renal cell carcinoma
      development and clinical outcomes.
AB  - PURPOSE: Renal cell carcinoma is the eighth most common cancer in the United
      States and clear cell renal carcinoma is the most common type. Many signaling
      pathways are implicated in clear cell renal carcinoma development, including the
      inflammation pathway. However, less is known about how gene expression variation
      in this pathway influences clear cell renal carcinoma development and clinical
      outcomes. MATERIALS AND METHODS: Gene expression in tumor and adjacent normal
      tissues from 93 patients was detected using a genome-wide expression array. A
      panel of 661 inflammation related genes was then analyzed. Differential
      expression patterns between tumor and normal tissues were identified. Association
      with recurrence or survival was evaluated with genes showing significant
      association tested further in a validation set of 258 tumors using an independent
      platform (quantitative real-time polymerase chain reaction). RESULTS: We
      identified 151 genes with at least a two-fold change in gene expression between
      adjacent normal tissue and tumor, of which most were up-regulated in tumors. A
      total of 20 genes significantly associated with recurrence and/or overall
      survival were selected for further validation. In the replication data set high
      expression of GADD45G was significantly associated with a 2.09-fold (95% CI 1.08
      6.14, p = 0.034) increased risk of recurrence while high CARD9, NCF2 and CIITA
      expression was significantly associated with a 2.52-fold (95% CI 1.24-5.12, p =
      0.010), 2.26-fold (95% CI 1.12-4.58, p = 0.023) and 2.11-fold (95% CI 1.05-4.27,
      p = 0.037) increased risk of death, respectively. CONCLUSIONS: Results suggest
      that inflammation gene expression may be significant prognostic biomarkers for
      the risk of recurrence (GADD45G) and death (CARD9, CIITA and NCF2) in patients
      with clear cell renal carcinoma.

PMID- 21944130
TI  - Predictive value of microtubule associated proteins tau and stathmin in patients
      with nonmuscle invasive bladder cancer receiving adjuvant intravesical taxane
      therapy.
AB  - PURPOSE: After encouraging results from 2 clinical trials performed at our
      institution to test intravesical taxane based chemotherapy for bacillus Calmette
      Guerin refractory, nonmuscle invasive bladder cancer we designed a study to
      identify molecular markers linked to the optimal response to such treatment
      modality. MATERIALS AND METHODS: Included in the institutional review board
      approved study were 32 patients with nonmuscle invasive, bacillus Calmette-Guerin
      refractory bladder cancer who received intravesical taxane chemotherapy, that is
      docetaxel or nanoparticle albumin-bound paclitaxel. Immunophenotype analysis on
      tissue samples obtained before intravesical taxane therapy was done using a panel
      of molecular markers, including Ki-67, p53, and the microtubule associated
      proteins tau and stathmin. RESULTS: Increased total tau (cytoplasmic and nuclear)
      and stathmin expression before intravesical taxane therapy was significantly
      associated with decreased recurrence-free survival (p <0.0001 and 0.007,
      respectively). A tau positive phenotype was an independent prognostic factor for
      recurrence-free survival on multivariate analysis (HR 15.66, 95% CI 2.68-91.71, p
      = 0.002). Neither the proliferation index assessed by Ki-67 expression nor p53
      status was significantly associated with recurrence-free survival. CONCLUSIONS:
      Assessment of tau and stathmin protein expression should be considered to select
      patients before intravesical taxane based chemotherapy for nonmuscle invasive,
      bacillus Calmette-Guerin refractory bladder cancer since those who have tumors
      with low tau/stathmin protein expression show a better response to therapy.

PMID- 21944132
TI  - Association of attention deficit and elimination disorders at school entry: a
      population based study.
AB  - PURPOSE: Attention deficit/hyperactivity disorder is a common comorbid disorder
      in children with nocturnal enuresis, daytime urinary incontinence and fecal
      incontinence. We assessed the specific association of these conditions in a
      population based sample. We hypothesized that children with elimination disorders
      have a higher rate of attention deficit/hyperactivity disorder, and that children
      with daytime urinary incontinence are more strongly affected than those with
      nocturnal enuresis. MATERIALS AND METHODS: All children in a defined geographic
      area (Saarpfalz Kreis) were examined at school entry. Mean age was 6.22 years in
      734 boys and 6.18 years in 645 girls. A questionnaire regarding elimination
      problems and the attention problems scale of the Child Behavior Checklist were
      administered as an interview to parents. Participation rate was 99.1% (1,379
      parents). RESULTS: Of the children 71 (5.1%) had attention deficit/hyperactivity
      disorder problems of clinical relevance (7.1% of boys and 2.9% of girls). A total
      of 185 children (13.4%) were wet (nocturnal enuresis in 9.1% and daytime urinary
      incontinence in 4.4%) and 19 (1.4%) had fecal incontinence. Attention
      deficit/hyperactivity disorder symptoms were more common in children with urinary
      incontinence than nonwetting children (16.8% vs 3.4%). When controlled for
      confounding variables, only children with daytime urinary incontinence (but not
      nocturnal enuresis) had a significantly higher risk of attention
      deficit/hyperactivity disorder symptoms (OR 4.4). CONCLUSIONS: Attention
      deficit/hyperactivity disorder symptoms were increased in children with urinary
      incontinence in this population based sample. Children with daytime urinary
      incontinence were at greater risk for attention deficit/hyperactivity disorder
      than those with nocturnal enuresis. Screening and referral for specialized
      treatment of both disorders are recommended.

PMID- 21944133
TI  - Phase IIb/III dose ranging study of tamsulosin as treatment for children with
      neuropathic bladder.
AB  - PURPOSE: We evaluated the efficacy and safety of tamsulosin hydrochloride in
      children with increased detrusor leak point pressure associated with neuropathic
      bladder. MATERIALS AND METHODS: In a double-blind, randomized, placebo controlled
      trial patients with detrusor leak point pressure 40 cm H(2)O or greater were
      stratified by age (2 to less than 5 years, 5 to less than 10 years, 10 to 16
      years) and concomitant anticholinergic use, and were randomized to receive
      various doses of tamsulosin or placebo. A 2-week titration was followed by a 12
      week maintenance treatment period. Primary end point was response, ie detrusor
      leak point pressure less than 40 cm H(2)O from 2 evaluations on the same day at
      week 14. Secondary end points included detrusor leak point pressure change from
      baseline, hydronephrosis and hydroureter responses, change in catheterization
      volumes and adverse events. RESULTS: A total of 161 patients received 1 or more
      treatment doses between January 2008 and February 2009, and 135 were evaluable
      for the primary end point. A total of 51 patients (37.8%) were detrusor leak
      point pressure responders, with no statistically significant difference in
      response rates between each tamsulosin dose and placebo. Adjusting for
      stratification variables, mean detrusor leak point pressure changes from baseline
      to week 14 for placebo and low, medium and high dose groups were -11.4, -17.6, 
      4.6 and -14.3 cm H(2)O, respectively. In 141 evaluable patients
      hydroureter/hydronephrosis improvement rates were 7.1% and 5.7% in left and right
      kidneys (hydroureter), respectively, and 14.9% and 14.2% in left and right
      kidneys (hydronephrosis), respectively. No group experienced decreases in median
      post-void residual volume at week 14. Drug related adverse event incidences were
      4.9% (placebo) and 5.8% (tamsulosin). CONCLUSIONS: Tamsulosin was well tolerated
      but not efficacious in this pediatric population with neuropathic bladder.

PMID- 21944134
TI  - Use of magnetic resonance imaging to accurately detect and stage prostate cancer:
      the hype and the hope.

PMID- 21944135
TI  - Is there a way to predict stress urinary incontinence after holmium laser
      enucleation of the prostate?
AB  - PURPOSE: In this study we defined high risk patients at high risk of stress
      urinary incontinence after holmium laser enucleation of the prostate. MATERIALS
      AND METHODS: We performed a retrospective analysis during a 10-year period of 949
      consecutive patients treated with holmium laser enucleation of the prostate by a
      single surgeon. Patients were divided into group 1--those without postoperative
      stress urinary incontinence (902) and group 2--those with stress urinary
      incontinence (47). All preoperative, intraoperative and postoperative clinical
      variables were compared between the 2 groups. RESULTS: Patient age, preoperative
      and postoperative prostate specific antigen, preoperative medications,
      preoperative acute retention and duration of postoperative catheter time were not
      associated with postoperative stress urinary incontinence. The presence of
      diabetes mellitus was significantly associated with a higher incidence of stress
      urinary incontinence (p <0.001). Using medians of the whole cohort, prostate
      volume greater than 81 gm, operative time greater than 96 minutes and reduction
      in prostate specific antigen greater than 84% were significantly associated with
      stress urinary incontinence. On multivariate analysis prostate volume greater
      than 81 gm, the presence of diabetes mellitus and greater than 84% reduction in
      prostate specific antigen remained statistically significant. CONCLUSIONS:
      Holmium laser enucleation of the prostate results in stress urinary incontinence
      at a rate comparable to that of other surgical techniques for the treatment of
      benign prostatic hyperplasia. The presence of diabetes mellitus, large prostate
      volume and a greater reduction in postoperative prostate specific antigen
      remained statistically significant for the development of stress urinary
      incontinence. Patients with diabetes, especially those with a large prostate,
      should be encouraged to start Kegel exercises in the immediate postoperative
      period.

PMID- 21944136
TI  - Complications after prostate biopsy: data from SEER-Medicare.
AB  - PURPOSE: More than 1 million prostate biopsies are performed annually among
      Medicare beneficiaries. We determined the risk of serious complications requiring
      hospitalization. We hypothesized that with emerging multidrug resistant organisms
      there may be an increasing risk of infectious complications. MATERIALS AND
      METHODS: In a 5% random sample of Medicare participants in SEER (Surveillance,
      Epidemiology and End Results) regions from 1991 to 2007 we compared 30-day
      hospitalization rates and ICD-9 primary diagnosis codes for admissions between
      17,472 men who underwent prostate biopsy and a random sample of 134,977 controls.
      Multivariate logistic and Poisson regression were used to examine the risk and
      predictors of serious infectious and noninfectious complications with time.
      RESULTS: The 30-day hospitalization rate was 6.9% within 30 days of prostate
      biopsy, which was substantially higher than the 2.7% in the control population.
      After adjusting for age, race, SEER region, year and comorbidities prostate
      biopsy was associated with a 2.65-fold (95% CI 2.47-2.84) increased risk of
      hospitalization within 30 days compared to the control population (p <0.0001).
      The risk of infectious complications requiring hospitalization after biopsy was
      significantly greater in more recent years (p(trend) = 0.001). Among men
      undergoing biopsy, later year, nonwhite race and higher comorbidity scores were
      significantly associated with an increased risk of infectious complications.
      CONCLUSIONS: The risk of hospitalization within 30 days of prostate biopsy was
      significantly higher than in a control population. Infectious complications after
      prostate biopsy have increased in recent years while the rate of serious
      noninfectious complications is relatively stable. Careful patient selection for
      prostate biopsy is essential to minimize the potential harms.

PMID- 21944137
TI  - Histological findings in patients with cryptorchidism and testis-epididymis
      nonfusion.
AB  - PURPOSE: Fusion anomalies of the testis and epididymis are associated with
      cryptorchidism. The bilateral histology of the cryptorchid testis associated with
      the nonfused epididymis has not been reported previously. MATERIALS AND METHODS:
      We retrospectively reviewed patients who presented with unilateral undescended
      testes and underwent bilateral testis biopsy at orchiopexy between 1982 and 2008.
      Testes were stratified into groups based on degree of testis-epididymis
      nonfusion. Age at surgery, testicular volume, testicular position, total germ
      cells per tubule and adult dark spermatogonia per tubule were compared among all
      groups. RESULTS: A total of 2,660 testes were eligible for review, of which 2,425
      had normal fusion (group 1), 55 had epididymal head nonfusion (group 2), 119 had
      epididymal tail nonfusion (group 3) and 61 had complete nonfusion (group 4). With
      increasing degrees of nonfusion trends toward younger age, smaller testicular
      volume and higher preoperative position were observed. However, testis-epididymis
      nonfusion was not a significant predictor of abnormal germ cells per tubule or
      adult dark spermatogonia per tubule in undescended testes and contralateral
      descended testes. CONCLUSIONS: Fusion anomalies are associated with smaller,
      higher testes with no significant abnormalities in germ cells per tubule or adult
      dark spermatogonia per tubule. Testis-epididymis nonfusion is not a reliable
      predictor of reduced histological findings, and should not be a strong
      consideration when counseling patients and their families about future fertility,
      especially in instances of complete nonfusion.

PMID- 21944138
TI  - Skill based mentored laparoscopy course participation leads to laparoscopic
      practice expansion and assists in transition to robotic surgery.
AB  - PURPOSE: Prior studies suggest poor long-term incorporation of laparoscopy into
      urology practice after a postgraduate course. We evaluated the influence of the
      American Urological Association Mentored Laparoscopy Course on urologist clinical
      practice. MATERIALS AND METHODS: The 2-day Mentored Laparoscopy Course includes
      lectures, standardized dry laboratory training with videotape analysis and a
      porcine laboratory with consistent mentors. Surveys to assess the impact of the
      course were sent in April 2010 to the 153 urologists who had taken the course
      from 2004 through 2009. RESULTS: Of the 153 surveys 91 (60%) were returned a mean
      of 34.5 months after completing the course. Of the respondents 82% were in a
      group private practice, followed by solo private practice (15%) and full-time
      academic practice (3%). Of the respondents 92% reported that they had sutured
      laparoscopically, 52% had sutured a bleeding vessel and 51% had performed
      reconstructive laparoscopy since taking the course. Of the respondents 77%
      reported that their laparoscopic practice had expanded since taking the course
      (mean 2.9 cases monthly). Of the 41 respondents (45%) who now performed robotic
      surgery (mean 3.8 cases monthly) 39 (95%) thought that the course experience had
      helped with the transition into robotic surgery. Overall survey respondents were
      pleased with the experience during the course with 89 of 91 (98%) stating that
      they would recommend the course to a colleague. CONCLUSIONS: Long-term results
      reveal that the American Urological Association Mentored Laparoscopy Course
      attendees reported expansion in their laparoscopic practice since taking the
      course. They described the course as benefiting the transition to robotic
      surgery.

PMID- 21944139
TI  - Effect of smoking status on seminal parameters and apoptotic markers in infertile
      men.
AB  - PURPOSE: We assessed semen parameters, sperm apoptotic markers and seminal plasma
      cotinine in infertile smokers. MATERIALS AND METHODS: A total of 160 men were
      divided into 4 equal groups, including fertile smokers, fertile nonsmokers,
      infertile smokers and infertile nonsmokers. Smoking was classified as mild--fewer
      than 10, moderate--10 to 20 or heavy--more than 20 cigarettes daily. All men
      underwent semen analysis, and assessment of sperm caspase-9, Smac/DIABLO, DNA
      fragmentation and seminal plasma cotinine. RESULTS: Infertile men, particularly
      smokers, have significantly lower semen variables and significantly higher sperm
      Smac/DIABLO, caspase-9 activity, the percent of DNA fragmentation and seminal
      plasma cotinine. The mean number of cigarettes smoked daily and smoking duration
      significantly correlated positively with sperm Smac/DIABLO, caspase-9 activity,
      the percent of DNA fragmentation and seminal plasma cotinine, and significantly
      correlated negatively with tested semen variables. Heavy smoking was associated
      with a significant increase in sperm Smac/DIABLO, caspase-9 activity and seminal
      plasma cotinine, and with a significant decrease in tested semen variables
      compared with those in moderate or mild smokers. CONCLUSIONS: Smoking has a
      negative impact on semen variables. It is associated with increased sperm caspase
      9, Smac/DIABLO and the percent of DNA fragmentation, especially in infertile
      heavy smokers.

PMID- 21944140
TI  - Impact of 3.5 cm artificial urinary sphincter cuff on primary and revision
      surgery for male stress urinary incontinence.
AB  - PURPOSE: We report our initial clinical experience with the new 3.5 cm artificial
      urinary sphincter cuff. MATERIALS AND METHODS: We reviewed the records of all men
      who underwent artificial urinary sphincter placement done by a single surgeon
      since September 2009. A perineal approach was used to ensure cuff placement
      around the most proximal corpus spongiosum after precise spongiosal measurement
      with a redesigned measuring tape. Clinical factors and cuff sizes were analyzed.
      RESULTS: During the 14-month study period 45 of 67 patients (67%) with an
      artificial urinary sphincter received the 3.5 cm cuff with no difference between
      primary and revision surgery (73% vs 58%, p = 0.29). Transcorporal cuff placement
      was reserved for 8 select patients (12%) after prior artificial urinary sphincter
      cuff erosion or complex urethroplasty. A tandem cuff artificial urinary sphincter
      was not used. Erectile dysfunction (89% vs 77%, p = 0.28) and prior radiation
      (47% vs 27%, p = 0.12) were more common in men who received a 3.5 vs a 4.0 cm or
      greater cuff. A similar proportion of men with a 3.5 cm vs a larger cuff (4 of 45
      or 9% vs 2 of 22 or 9%) required explantation for infection and/or erosion.
      CONCLUSIONS: At our center the 3.5 cm cuff has become the predominant size used
      for primary and revision artificial urinary sphincter placement. Liberal use of
      the 3.5 cm cuff has simplified and improved artificial urinary sphincter
      placement without additional morbidity.

PMID- 21944142
TI  - Evaluation of clinical and magnetic resonance imaging results after treatment
      with casting and bracing for the acutely injured posterior cruciate ligament.
AB  - PURPOSE: The purpose of this study was to evaluate the clinical and magnetic
      resonance imaging (MRI) outcomes of nonoperative management of acute, isolated
      posterior cruciate ligament (PCL) injuries. METHODS: From February 2001 to
      January 2008, 49 consecutive patients with acute (<4 weeks), isolated PCL
      injuries underwent nonoperative treatment with cast immobilization and PCL
      braces. Of these patients, 38 who satisfied our inclusion criteria and could be
      followed up for a minimum of 24 months (median, 51 months) were enrolled in our
      study. Functional outcomes were evaluated at follow-up with the Lysholm knee
      scoring system, Hospital for Special Surgery knee scoring system, and
      International Knee Documentation Committee subjective and objective knee scoring
      systems. PCL injury status on MRI was assessed using a different scale for
      initial and follow-up MRI. RESULTS: The grade of posterior instability was
      significantly improved from initial grades of I in 13 patients (34%) and II in 25
      patients (66%) to follow-up grades of 0 in 3 patients (8%), I in 21 patients
      (55%), and II in 14 patients (37%) (P = .007). The mean side-to-side difference
      in posterior translation measured with the KT-1000 arthrometer (MEDmetric, San
      Diego, CA) was initially 6.7 mm and significantly improved to 5.2 mm at the
      latest follow-up (P < .001). At latest follow-up, the mean Lysholm knee score,
      Hospital for Special Surgery knee score, and International Knee Documentation
      Committee subjective score were 88, 91, and 83, respectively. The continuity of
      the PCL on follow-up MRI showed statistically less posterior instability on both
      physical examination (P = .010) and KT-1000 arthrometer testing (P = .003).
      CONCLUSIONS: Our active, nonoperative method of casting and bracing with attached
      tibial supporters, which was designed to prevent posterior displacement at the
      knee, yielded satisfactory functional and MRI results in the majority of patients
      at intermediate-term follow-up. The continuity of the PCL with low signal
      intensity on follow-up MRI was a predictable factor for a favorable prognosis in
      patients with acute PCL injuries. LEVEL OF EVIDENCE: Level IV, therapeutic case
      series.

PMID- 21944143
TI  - Colchicine in acute pericarditis: a new standard?

PMID- 21944144
TI  - Modelling of blood pressure and total cardiovascular risk outcomes after second
      line valsartan therapy: the BSCORE study.
AB  - BACKGROUND: European guidelines recommend that antihypertensive management should
      be graded as a function of total cardiovascular risk. AIMS: To examine the
      multilevel (patient- and physician-level) determinants of blood pressure and
      residual total cardiovascular risk outcomes associated with second-line valsartan
      therapy. METHODS: The BSCORE study was a prospective, multi-centre,
      pharmacoepidemiological study of the "real-world" effectiveness of second-line
      valsartan with or without hydrochlorothiazide. RESULTS: A total of 3497 patients
      were recruited by 354 physicians. Mean age was 63.8+/-12.0 years; 52.3% were
      male; 20.9% were smokers; 47.7% were dyslipidaemic; and 23.6% had diabetes. On
      average, reductions in blood pressure and increases in the proportions of
      patients with controlled blood pressure after 90 days were statistically
      significant (all P<0.001). Twenty-one percent of systolic blood pressure and
      25.6% of diastolic blood pressure variability at follow-up was attributable to
      physician-level characteristics. Significant reductions in total cardiovascular
      risk were observed (P<0.001); with 12.5% of the variability in total
      cardiovascular risk change attributable to physician-level characteristics.
      Several independent determinants of blood pressure outcomes were identified, many
      of which are modifiable. CONCLUSIONS: Second-line valsartan therapy improves
      blood pressure outcomes under variable real-world conditions, and is associated
      with a decrease in total cardiovascular risk. Optimizing antihypertensive
      effectiveness, including the reduction of residual cardiovascular risk, involves
      managing concomitant conditions and risk factors, improving adherence, and
      identifying physician-level factors amenable to intervention.

PMID- 21944145
TI  - Initial hospital pulse pressure and cardiovascular outcomes in acute coronary
      syndrome.
AB  - BACKGROUND: The association between admission pulse pressure (PP) and
      cardiovascular outcomes in acute coronary syndrome (ACS) is not well defined.
      AIM: To explore the prognostic value of initial PP in ST-segment elevation
      myocardial infarction (STEMI) and non-ST elevation ACS (NSTE-ACS). METHODS: Over
      a 5-month period in 2007, 6704 consecutive patients with ACS were categorized
      into five groups according to initial PP: P1, PP <=0; P2, PP 31-40; P3, PP 41-50;
      P4, PP 51-60; P5, PP>60mmHg. Patient characteristics and in-hospital outcomes
      were analysed. RESULTS: Mean PP was lower in men versus women (55+/-19 vs. 61+/
      22), young versus old (53+/-17 vs. 59+/-21), STEMI vs. NSTE-ACS (51+/-18 vs. 60+/
      18) and patients who died versus survived (46+/-22 vs. 57+/-19mmHg) (P<0.001 for
      all). Most patients with low PP had a high Global Registry of Acute Coronary
      Events risk score. Compared with P5, crude odds ratios (ORs) (95% confidence
      intervals) for death were: P1, 9 (5.78-13.35); P2, 3 (1.71-4.06); P3, 1.5 (1.01
      2.49); P4, 0.90 (0.51-1.58). After adjustment, low PP was associated with high
      mortality and stroke rates in ACS (adjusted ORs 7.5 [3.77-14.72] and 4.5 [1.20
      18.88], respectively), high rates of recurrent ischaemia in NSTE-ACS (adjusted OR
      2.8 [1.52-5.22]) and a high heart failure rate in STEMI (adjusted OR 2.1 [1.18
      3.76]). Women with low PP had a higher mortality rate than men. CONCLUSION: In
      ACS, all blood pressure variables were significantly correlated. Low PP was an
      independent predictor for stroke and mortality in overall ACS. Although PP was
      not superior to systolic blood pressure, only low PP was an independent predictor
      for recurrent ischaemia in NSTE-ACS.

PMID- 21944146
TI  - Transradial approach and subclavian wired temporary pacemaker to increase safety
      of alcohol septal ablation for treatment of obstructive hypertrophic
      cardiomyopathy: the TRASA trial.
AB  - BACKGROUND: Alcohol septal ablation (ASA) is a therapeutic catheter-based option
      and an alternative to surgical myectomy in the treatment of patients with
      hypertrophic obstructive cardiomyopathy. Although the safety of the ASA procedure
      has been consistently improved, a temporary transvenous pacemaker is recommended
      for at least 48h postprocedure, with several drawbacks, including the risk of
      cardiac perforation and infection, and the absence of any fixation mechanism. In
      addition, femoral artery catheterization has resulted in a concomitant increase
      in bleedings and iatrogenic femoral artery injuries. AIMS: To evaluate and
      validate the feasibility of less invasive management of ASA using the transradial
      approach and a subclavian wired temporary pacemaker. METHODS: To avoid
      transfemoral temporary pacing, we used a subclavian bipolar active-fixation
      permanent pacing lead, stitched to the skin and connected to a desterilized
      recuperation pacemaker. The day before discharge, if there was no high-degree
      atrioventricular block, the pacemaker lead was removed. In all patients, we used
      the right radial access and the left main was cannulated with a 6F Judkins left
      3.5 guiding catheter. RESULTS: Thirty consecutive patients were prospectively and
      successfully included in our study. No complication was observed during the
      hospital stay, neither access-site nor stimulation-lead related. CONCLUSIONS: Our
      study shows the feasibility and safety of a transradial approach and a subclavian
      wired temporary pacemaker. The reduction in periprocedural complications offered
      by this strategy reflects the less invasive nature of ASA, without increasing the
      cost and complexity of the procedure.

PMID- 21944147
TI  - Acute pericardial effusion following atrial fibrillation ablation:
      characteristics and relationship with arrhythmia recurrences.
AB  - BACKGROUND: Pericardial effusion (PE) can occur during or after atrial
      fibrillation (AF) ablation, and may induce atrial arrhythmia. AIM: To
      characterize the impact of PE on arrhythmia recurrences following AF ablation.
      METHODS: Patients referred for a first radiofrequency AF ablation were studied
      prospectively. Transthoracic echocardiography was performed before and 24h after
      the procedure. If PE was present, transthoracic echocardiography was repeated at
      1 month to evaluate PE evolution. Early arrhythmia recurrences (EARs) were
      defined as any arrhythmia documented within 1 month of the procedure. RESULTS: PE
      was diagnosed in 18/81 patients (22%); and was present in significantly more
      patients with persistent versus paroxysmal AF (14/40 [35%] vs 4/41 [10%];
      P=0.008). PEs were mild (mean 6 +/- 3mm), mainly asymptomatic (89%), and none
      required pericardiocentesis. Early and late arrhythmia recurrences were present
      in 25/81 (31%) and 29/81 (36%), respectively. The incidence of PE was
      significantly higher among patients with EARs versus those without (12/25 [48%]
      vs 6/56 [11%]; P=0.0004). By multivariable analysis, PE and duration in AF were
      the two independent predictors of EARs. PE incidence was similar in patients with
      and without late arrhythmia recurrences. At 1 month, no patients had PE on
      transthoracic echocardiography. CONCLUSION: PE following radiofrequency AF
      ablation is frequent, particularly following persistent AF ablation. This
      effusion is generally mild, mainly asymptomatic, and independently associated
      with EARs.

PMID- 21944148
TI  - Preliminary experience with Impella Recover((r)) LP5.0 in nine patients with
      cardiogenic shock: a new circulatory support system in the intensive cardiac care
      unit.
AB  - AIM: Cardiogenic shock is associated with high mortality. We report our
      experience with the short-term left ventricular axial pump Impella LP5.0 in nine
      patients with severe ischaemic heart failure. METHODS: Six patients (group 1)
      presented with cardiogenic shock at the acute phase of an ST elevation myocardial
      infarction. Three patients (group 2) had severe ischaemic cardiomyopathy with
      temporary contra-indication to LVAD or transplantation. We measured haemodynamic
      and metabolic variables up to 96hours and recorded morbidity, mechanical pump
      failures, and mortality up to one year postimplantation. RESULTS: In all patients
      the Impella LP5.0 was safely placed through the right subclavian artery. Cardiac
      power output increased from 0.64 (0.07) W to 0.94 (0.44) W and 1.02 (0.30) W at
      24 and 72hours, respectively. The Impella LP5.0 remained in place for 12 (7.2)
      days. In group 1, five patients were in INTERMACS Profile 3 at the time of pump
      insertion. Three could be weaned and survived. One patient in INTERMACS Profile 1
      died of intractable heart failure within hours. In group 2, two of three patients
      underwent heart transplantation. Haemorrhage requiring transfusions was observed
      in four patients but only one case was directly related to the Impella LP5.0.
      CONCLUSION: Left ventricular assistance with the Impella LP5.0 appears to be well
      tolerated. It may be especially useful in patients with acute myocardial
      infarction complicated by cardiogenic shock who achieve INTERMACS Profile 3 with
      initial treatment.

PMID- 21944149
TI  - Congenital malformations of the mitral valve.
AB  - Congenital malformations of the mitral valve may be encountered in isolation or
      in association with other congenital heart defects. Each level of the mitral
      valve complex may be affected, according to the embryological development,
      explaining the fact that these lesions are sometimes associated with each other.
      As a perfect preoperative assessment is of importance, good knowledge of both
      normal and abnormal anatomy is required in order to guide the surgeon accurately.
      This review presents the different embryological, anatomical and
      echocardiographic aspects of the congenital mitral anomalies.

PMID- 21944150
TI  - Sudden death caused by atypical variant angina.

PMID- 21944151
TI  - Temporomandibular joint dislocation during transoesophageal echocardiography: an
      unusual complication.

PMID- 21944152
TI  - Carotid glomectomy: a treatment for syncope?

PMID- 21944153
TI  - Iatrogenic aortic valve perforation assessed using three-dimensional
      transoesophageal echocardiography.

PMID- 21944155
TI  - Cell-free fetal nucleic acid testing: a review of the technology and its
      applications.
AB  - Cell-free fetal nucleic acids circulating in the blood of pregnant women afford
      the opportunity for early, noninvasive prenatal genetic testing. The predominance
      of admixed maternal genetic material in circulation demands innovative means for
      identification and analysis of cell-free fetal DNA and RNA. Techniques using
      polymerase chain reaction, mass spectrometry, and sequencing have been developed
      for the purposes of detecting fetal-specific sequences, such as paternally
      inherited or de novo mutations, or determining allelic balance or chromosome
      dosage. Clinical applications of these methods include fetal sex determination
      and blood group typing, which are currently available commercially although not
      offered routinely in the United States. Other uses of cell-free fetal DNA and RNA
      being explored are the detection of single-gene disorders, chromosomal
      abnormalities, and inheritance of parental polymorphisms across the whole fetal
      genome. The concentration of cell-free fetal DNA may also provide predictive
      capabilities for pregnancy-associated complications. The roles that cell-free
      fetal nucleic acid testing assume in the existing framework of prenatal screening
      and invasive diagnostic testing will depend on factors such as costs, clinical
      validity and utility, and perceived benefit-risk ratios for different
      applications. As cell-free fetal DNA and RNA testing continues to be developed
      and translated, significant ethical, legal, and social questions will arise that
      will need to be addressed by those with a stake in the use of this technology.
      TARGET AUDIENCE: Obstetricians & Gynecologists and Family Physicians Learning
      Objectives: After participating in this activity, physicians should be better
      able to evaluate techniques and tools for analyzing cell-free fetal nucleic
      acids, assess clinical applications of prenatal testing, using cell-free fetal
      nucleic acids and barriers to implementation, and distinguish between relevant
      clinical features of cell-free fetal nucleic acid testing and existing prenatal
      genetic screening and diagnostic procedures.

PMID- 21944156
TI  - Fertility-sparing management of endometrial adenocarcinoma.
AB  - Approximately 15% of patients with endometrial cancer are premenopausal. Previous
      studies largely support the conservative treatment of endometrial cancer in women
      desiring future fertility. From these studies, 75% to 80% of patients demonstrate
      a complete response to progestin therapy and the average recurrence rate is 30%
      to 35%. Conservative therapy should be reserved for women with International
      Federation of Gynecology and Obstetrics grade I tumors. Before conservative
      management, patients should be informed of the elevated risk (11%-29%) of
      concurrent ovarian cancer in cases of premenopausal endometrial cancer, and
      screening and ongoing surveillance during the treatment period is mandatory. A
      suggestion of myometrial invasion or metastatic disease is a contraindication to
      conservative management. Individuals meeting criteria for Lynch syndrome testing
      should be referred to genetic counseling. Fertility treatment should be
      individualized, and close surveillance is required during treatment. Staging
      hysterectomy is recommended after the completion of the childbearing period.
      TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians Learning
      Objectives: After participating in this activity, physicians should be better
      able to select appropriate candidates with endometrial cancer for fertility
      sparing treatment. Educate patients with endometrial cancer regarding the risks
      and benefits of standard of care therapy and conservative therapy and screen
      appropriate patients for Lynch syndrome.

PMID- 21944157
TI  - Geophagy during pregnancy in Africa: a literature review.
AB  - INTRODUCTION: Geophagy is a form of pica characterized by craving and eating of
      soil. The main materials ingested include anthill soils and soft stone. In this
      review, our objectives were to study the prevalence of geophagy in pregnancy
      (GiP), establish the risk factors for GiP, assess the effects of GiP on pregnancy
      outcomes, and recommend possible interventions for reducing GiP. PREVALENCE:
      Geophagy among pregnant women is common in many cultures. In some African
      countries, GiP prevalence of up to 84% has been observed. In Nigeria, the most
      populous country in Africa, the prevalence of GiP is estimated at 50%. The
      practice has been associated with religious practice, culture, and famine. RISKS:
      It is postulated that GiP is due to micronutrient deficiencies, cultural
      influences, and gastrointestinal upsets. Despite their potential to supply
      micronutrients, soils interfere with bioavailability of micronutrients leading to
      micronutrient deficiency and can also act as a pathway for ingestion of
      geohelminths and heavy metals, putting woman and fetus at risk. GAPS: Despite its
      association with anemia, pregnancy, and micronutrients, many antenatal care
      guidelines or National guidelines on micronutrient deficiency control are silent
      on GiP. The guidelines generally recommend iron supplementation and deworming of
      pregnant women as anemia control measures. However, not all women seek antenatal
      services; hence, there is need for more innovative ways of addressing
      micronutrient deficiencies in pregnancy. RECOMMENDATIONS: It is imperative to
      enquire whether pregnant women are geophagous and discourage geophagy, strengthen
      and expand the existing supplementation programs, and mandate flour fortification
      to enhance population-wide iron supply and safer pregnancies. TARGET AUDIENCE:
      Obstetricians & Gynecologists and Family Physicians. LEARNING OBJECTIVES: After
      completing this CME activity, physicians should be better able to analyze the
      prevalence of GiP, identify the risk factors for GiP, and assess the effects of
      GiP on pregnancy outcomes. In addition to propose remedial interventions for
      reducing GiP.

PMID- 21944154
TI  - Functional brain activation during retrieval of visceral pain-conditioned passive
      avoidance in the rat.
AB  - This study assessed functional brain activation in rats during expectation of
      visceral pain. Male rats were trained in step-down passive avoidance (PA) for 2
      days. Upon stepping down from a platform, conditioned animals received noxious
      colorectal distension delivered through a colorectal balloon, whereas the balloon
      in control rats remained uninflated. On day 3, PA behavior was assessed while
      [(14)C]-iodoantipyrine was infused intravenously, followed by immediate
      euthanasia. Regional cerebral blood flow-related tissue radioactivity (rCBF) was
      analyzed by statistical parametric mapping using 3-dimensional brains
      reconstructed from autoradiographic brain slice images. Associated with retrieved
      PA behavior, conditioned rats compared with control subjects showed increases in
      rCBF in sensory (anterior insula, somatosensory cortex), limbic/paralimbic
      regions (anterior cingulate, prelimbic cortex, amygdala), all regions previously
      reported to show activation during acute visceral pain. Increases in rCBF were
      also noted in the dorsal hippocampus, nucleus accumbens, and caudate putamen,
      regions associated with retrieval of PA. Organization of the underlying brain
      network was further delineated by functional connectivity analysis. This revealed
      in conditioned rats a strongly and positively connected corticostriatal cluster
      (cingulate, prelimbic cortex, caudate putamen). The amygdala and cerebellar
      hemispheres formed another positively connected cluster, which was negatively
      connected with the corticostriatal cluster, suggesting corticolimbic modulation.
      Prelimbic cortex, nucleus accumbens, and anterior insula emerged in conditioned
      animals as hubs. Our results show that during retrieval of PA, brain areas
      implicated in PA expression as well as those implicated in acute visceral pain
      processing were recruited, in line with findings from human brain imaging studies
      on pain expectation.

PMID- 21944158
TI  - Face to face or cyberspace: are online meetings better?

PMID- 21944159
TI  - Antimicrobial use and risk for recurrent Clostridium difficile infection.
AB  - BACKGROUND: Although antimicrobial use during and immediately after Clostridium
      difficile infection (CDI) is discouraged, the frequency and consequences of such
      use are poorly defined. We sought to determine the frequency of non-CDI
      antimicrobial therapy during and after treatment for CDI, and the association of
      such therapy with recurrent disease. METHODS: Retrospective review of all CDI
      cases at a Veterans Affairs medical center from 2004-2006. Outcomes were non-CDI
      antimicrobial use during and within 30 days after completing CDI treatment, and
      recurrent CDI. RESULTS: From 2004 to 2006, new-onset CDI occurred in 249 unique
      patients. No follow-up information was available for 3 patients, leaving 246 as
      study subjects. Of these, 141 (57%) received non-CDI antimicrobials, including 61
      (25%) who received non-CDI antimicrobials during CDI treatment, and 80 (33%) who
      received non-CDI antimicrobial therapy after CDI treatment. With adjustment for
      age, disease severity, duration of CDI treatment, and recent hospital or
      intensive-care unit stay, receipt of non-CDI antimicrobials after CDI treatment
      was significantly associated with recurrent CDI (odds ratio [OR] 3.02; 95%
      confidence interval [CI], 1.66-5.52), compared with no antimicrobial use.
      Antimicrobial use during CDI treatment was not associated with recurrent CDI (OR
      0.79; 95% CI, 0.40-1.52). Neither number of antimicrobial courses nor
      antimicrobial days was associated with recurrence. CONCLUSIONS: Non-CDI
      antimicrobial therapy after an episode of CDI is common and is associated with a
      3-fold increase in the odds of recurrent disease. The added risk associated with
      antimicrobial exposure (regardless of duration) should be considered if such
      therapy is contemplated.

PMID- 21944160
TI  - Dry eye syndrome: an update in office management.
AB  - Dry eye syndrome is a multifactorial disease of the ocular surface and tear film
      that results in ocular discomfort, visual disturbances, and tear instability,
      with potential damage to the cornea and conjunctiva. Risk factors for dry eye
      syndrome include age (>50 years old), female sex, environments with low humidity,
      systemic medications, and autoimmune disorders. There are several treatment
      options that range from artificial tears to anti-inflammatory and
      immunosuppressant agents. Treatment of this highly prevalent condition can
      drastically improve the quality of life of individuals and prevent damage to the
      ocular surface.

PMID- 21944161
TI  - Bedside assessment of cardiac hemodynamics: the impact of noninvasive testing and
      examiner experience.
AB  - BACKGROUND: Knowledge of cardiac filling pressures is critical in the diagnosis
      and management of patients with dyspnea or heart failure. Echocardiography and B
      natriuretic peptide (BNP) testing are commonly used to estimate these pressures,
      but their incremental value beyond physical examination remains unknown. METHODS:
      Right and left heart filling pressures were prospectively estimated as "normal"
      or "abnormal" by staff cardiologists and cardiovascular trainees based upon
      physical examination findings alone, or examination coupled with
      echocardiographic and BNP data in patients referred for cardiac catheterization.
      Net reclassification improvement was calculated to determine whether
      echocardiographic/BNP data had incremental value in the determination of right
      and left heart pressures. RESULTS: Two hundred fifteen observations were made by
      9 examiners in 116 consecutive patients. Right and left heart pressures were
      accurately predicted from examination alone in 71% and 60% of observations,
      respectively. Examination-based accuracy was greater for staff cardiologists
      compared with trainees for right heart (82 vs 67%, P=.03) and left heart
      pressures (71% vs 55%, P=.03). Exposure to echocardiographic and BNP data did not
      enhance accuracy beyond bedside examination alone, both for left heart pressures
      (net reclassification improvement=-0.004; 95% confidence interval, -0.12-0.12)
      and right heart pressures (net reclassification improvement=0.02, 95% confidence
      interval, -0.09-0.13). CONCLUSIONS: Cardiac filling pressures can be estimated
      from physical examination with modest accuracy, which is enhanced with
      experience. While echocardiographic and BNP data predict cardiac filling
      pressures, they may not provide information of incremental value beyond
      examination alone. Rigorous teaching and practice of cardiac examination skills
      should continue to be emphasized during medical training.

PMID- 21944162
TI  - A rare shock.

PMID- 21944163
TI  - [Technical and functional standards and implementation of a clinical information
      system in intensive care units].
AB  - INTRODUCTION: Clinical Information Systems (CIS) are becoming a useful tool for
      managing patients and data in the ICU. However, the existing CIS differ in their
      capabilities and technical requirements. It is therefore essential for
      intensivists, as the end clients of these applications, to define the suitable
      minimum specifications required in order to be operative and helpful. OBJECTIVES:
      The Spanish Society of Intensive Care Medicine and Coronary Units, through its
      Organization and Management Workgroup, has designated a group of clinical and
      software experts to draft a document with the recommendable technical and
      operating requirements of these systems. METHODS: The group was formed by ten
      people supported by managers or engineers from the five principal industries
      producing CIS in Spain. The project involved the following phases: a) Completion
      of a check list. This step was considered necessary in order to establish the
      precise current situation of CIS applications. b) Discussion of the results by
      the group of experts in a meeting and in online format. RESULTS: The requirements
      were grouped into four sections: technical, functional, safety and data
      management. All requirements were classified as basic and optional in order to
      allow the end user to choose among different options according to the existing
      budget, though ensuring a minimal set of useful characteristics. A chronogram for
      the installation process was also proposed.

PMID- 21944164
TI  - Strong coherence between heart rate variability and intracardiac repolarization
      lability during biventricular pacing is associated with reverse electrical
      remodeling of the native conduction and improved outcome.
AB  - BACKGROUND: Reverse electrical remodeling (RER) of the native conduction with
      cardiac resynchronization therapy (CRT) is associated with decreased mortality
      and antiarrhythmic effect of CRT. Still, mechanisms of RER are largely unknown.
      In this study, we explored repolarization lability during biventricular pacing.
      METHODS AND RESULTS: The width of native QRS was measured in lead II
      electrocardiogram before and at least 6 months after implantation of Cardiac
      Resynchronization Therapy Defibrillator (CRT-D) devices (Medtronic, Inc
      [Minneapolis, MN, USA] and Boston Scientific Corporate [Natick, MA, USA]) in 69
      patients (mean age, 66.3 +/- 13.9 years; 39 men [83%]) with either bundle-branch
      block (44 patients [64%]) or nonspecific intraventricular conduction delay (25
      patients [36%]) and New York Heart Association class III and IV heart failure.
      Narrowing of the native QRS duration for at least 10 milliseconds was considered
      a marker of RER. Beat-to-beat QT variability and coherence was measured on
      surface electrocardiogram and intracardiac near-field electrogram during
      biventricular pacing. Reverse electrical remodeling was observed in 22 patients
      (32%) in whom coherence between heart rate variability and intracardiac
      repolarization lability was stronger (0.483 +/- 0.243 vs 0.237 +/- 0.146, P =
      .018) and normalized intracardiac QT variance was smaller (0.28 +/- 0.0031 vs
      0.46 +/- 0.0048, P = .049), as compared with that in patients without RER. During
      a further 24 +/- 13 months of follow-up, 21 patients (33%) died or experienced
      sustained ventricular tachycardia (VT)/ventricular fibrillation. Low intracardiac
      coherence (<=0.116) was associated with increased risk of death or sustained
      VT/VT (hazard ratio, 4.33; 95% confidence interval, 1.51-12.40; P = .006).
      CONCLUSION: Strong coherence between heart rate variability and intracardiac
      repolarization lability during biventricular pacing is associated with RER of the
      native conduction with CRT. Low coherence is associated with increased risk of
      VT/ventricular fibrillation or death.

PMID- 21944165
TI  - Preface for special issue: EWOMS 2009.

PMID- 21944166
TI  - Spatial receptive field properties of rat retinal ganglion cells.
AB  - The rat is a popular animal model for vision research, yet there is little
      quantitative information about the physiological properties of the cells that
      provide its brain with visual input, the retinal ganglion cells. It is not clear
      whether rats even possess the full complement of ganglion cell types found in
      other mammals. Since such information is important for evaluating rodent models
      of visual disease and elucidating the function of homologous and heterologous
      cells in different animals, we recorded from rat ganglion cells in vivo and
      systematically measured their spatial receptive field (RF) properties using spot,
      annulus, and grating patterns. Most of the recorded cells bore likeness to cat X
      and Y cells, exhibiting brisk responses, center-surround RFs, and linear or
      nonlinear spatial summation. The others resembled various types of mammalian W
      cell, including local-edge-detector cells, suppressed-by-contrast cells, and an
      unusual type with an ON-OFF surround. They generally exhibited sluggish
      responses, larger RFs, and lower responsiveness. The peak responsivity of brisk
      nonlinear (Y-type) cells was around twice that of brisk-linear (X-type) cells and
      several fold that of sluggish cells. The RF size of brisk-linear and brisk
      nonlinear cells was indistinguishable, with average center and surround diameters
      of 5.6 +/- 1.3 and 26.4 +/- 11.3 deg, respectively. In contrast, the center
      diameter of recorded sluggish cells averaged 12.8 +/- 7.9 deg. The homogeneous RF
      size of rat brisk cells is unlike that of cat X and Y cells, and its implication
      regarding the putative roles of these two ganglion cell types in visual signaling
      is discussed.

PMID- 21944167
TI  - Selective translation of leaderless mRNAs by specialized ribosomes generated by
      MazF in Escherichia coli.
AB  - Escherichia coli (E. coli) mazEF is a stress-induced toxin-antitoxin (TA) module.
      The toxin MazF is an endoribonuclease that cleaves single-stranded mRNAs at ACA
      sequences. Here, we show that MazF cleaves at ACA sites at or closely upstream of
      the AUG start codon of some specific mRNAs and thereby generates leaderless
      mRNAs. Moreover, we provide evidence that MazF also targets 16S rRNA within 30S
      ribosomal subunits at the decoding center, thereby removing 43 nucleotides from
      the 3' terminus. As this region comprises the anti-Shine-Dalgarno (aSD) sequence
      that is required for translation initiation on canonical mRNAs, a subpopulation
      of ribosomes is formed that selectively translates the described leaderless mRNAs
      both in vivo and in vitro. Thus, we have discovered a modified translation
      machinery that is generated in response to MazF induction and that probably
      serves for stress adaptation in Escherichia coli.

PMID- 21944168
TI  - Effects of high-intensity progressive resistance training and targeted
      multidisciplinary treatment of frailty on mortality and nursing home admissions
      after hip fracture: a randomized controlled trial.
AB  - RATIONALE: Excess mortality and residual disability are common after hip
      fracture. HYPOTHESIS: Twelve months of high-intensity weight-lifting exercise and
      targeted multidisciplinary interventions will result in lower mortality, nursing
      home admissions, and disability compared with usual care after hip fracture.
      DESIGN: Randomized, controlled, parallel-group superiority study. SETTING:
      Outpatient clinic PARTICIPANTS: Patients (n = 124) admitted to public hospital
      for surgical repair of hip fracture between 2003 and 2007. INTERVENTION: Twelve
      months of geriatrician-supervised high-intensity weight-lifting exercise and
      targeted treatment of balance, osteoporosis, nutrition, vitamin D/calcium,
      depression, cognition, vision, home safety, polypharmacy, hip protectors, self
      efficacy, and social support. OUTCOMES: Functional independence: mortality,
      nursing home admissions, basic and instrumental activities of daily living
      (ADLs/IADLs), and assistive device utilization. RESULTS: Risk of death was
      reduced by 81% (age-adjusted OR [95% CI] = 0.19 [0.04-0.91]; P < .04) in the
      HIPFIT group (n = 4) compared with usual care controls (n = 8). Nursing home
      admissions were reduced by 84% (age-adjusted OR [95% CI] = 0.16 [0.04-0.64]; P <
      .01) in the experimental group (n = 5) compared with controls (n = 12). Basic
      ADLs declined less (P < .0001) and assistive device use was significantly lower
      at 12 months (P = .02) in the intervention group compared with controls. The
      targeted improvements in upper body strength, nutrition, depressive symptoms,
      vision, balance, cognition, self-efficacy, and habitual activity level were all
      related to ADL improvements (P < .0001-.02), and improvements in basic ADLs,
      vision, and walking endurance were associated with reduced nursing home use (P <
      .0001-.05). CONCLUSION: The HIPFIT intervention reduced mortality, nursing home
      admissions, and ADL dependency compared with usual care.

PMID- 21944169
TI  - Decreased plasma brain-derived neurotrophic factor levels in institutionalized
      elderly with depressive disorder.
AB  - OBJECTIVES: To compare the differences in plasma brain-derived neurotrophic
      factor (BDNF) levels among institutionalized ethnic Chinese elderly participants
      with major depression, those with subclinical depression, and a nondepressed
      control group. DESIGN: A cross-sectional study. SETTING: The veterans' home in
      southern Taiwan. PARTICIPANTS: One hundred sixty-seven residents. MEASUREMENTS:
      Questionnaires including the Minimum Data Set Nursing Home 2.1, Chinese-language
      version, and the short-form Geriatric Depression Scale, Chinese-language version.
      Depressive disorder was diagnosed by a well-trained psychiatrist using DSM-IV-TR
      (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text
      revision) criteria. We measured plasma BDNF levels in the following 3 groups:
      nondepressive subjects (n = 122), subclinically depressive subjects (n = 33), and
      subjects with major depression (n = 12). Plasma BDNF was assayed using the
      sandwich ELISA method. RESULTS: We noted a significantly negative association
      between age and plasma BDNF in the regression model. There was no significant
      correlation between BDNF plasma levels and body weight or platelet counts. We
      found that plasma BDNF was significantly lower in the major depressive group
      (mean, 115.1 pg/mL; SD, 57.2) than in the nondepressive group (mean, 548.8 pg/mL;
      SD, 370.6; P < .001). The BDNF plasma concentrations in the subclinically
      depressive group (mean, 231.8 pg/mL; SD, 92.4; P < .001) and control group were
      also significantly different. CONCLUSIONS: Our findings revealed that plasma BDNF
      levels were reduced not only in ethnic Chinese elderly patients with major
      depressive disorder but also in those with subclinical depression. This makes the
      plasma BDNF level a potential biological marker for clinical or subclinical
      depression.

PMID- 21944170
TI  - [Efficacy of heat and moisture exchangers and heated humidifiers in preventing
      ventilator-associated pneumonia: a meta-analysis].
AB  - OBJECTIVE: To demonstrate the effects of heat and moisture exchangers (HME) and
      heated humidifiers(HH) in preventing ventilator-associated pneumonia (VAP).
      METHODS: PubMed and Cochrane databases were searched by computer retrieval and
      manual retrieval to identify relevant randomized controlled trials (RCTs) using
      HMEs and HHs in preventing VAP from January 1st 1990 to September 1st 2010. Meta
      analysis of HME and HH in preventing VAP was conducted using the methods
      recommended by the Cochrane Collaboration. RESULTS: Eleven RCTs were included.
      SAMPLE SIZE: 1 121 in HME group and 1 101 in HH group. In total, the rate of VAP
      in HME group and HH group was 14.2% (159/1 121) and 15.9% (175/1 101)
      respectively, the total relative risk (RR) was 0.88, and 95% confidence interval
      (95%CI) 0.72-1.07, P=0.21. Compared with HH group, there was not a reduction in
      the risk ratio of VAP in the HME group. Even in mechanical ventilation(MV) with a
      duration of at least 7 days for subgroup analysis (8 RCTs, sample size: 834 in
      HME group and 859 in HH group), the rate of VAP in HME group and HH group was
      15.2% (127/834) and 17.5% (150/859) respectively, the total RR was 0.84, 95%CI 0.
      58-1.23, P=0.37, suggesting that in MV with a duration at least 7 days, there was
      also no reduction in the risk ratio of VAP in the HME group. CONCLUSION: This
      study suggests there is not a significant reduction in the incidence of VAP in
      patients humidified with HMEs during MV, even in patients ventilated for 7 days
      or longer. This finding is limited by lack of enough RCTs and blinding. Further
      large sample of high quality RCTs is necessary to examine the wider applicability
      of HMEs and their extended use.

PMID- 21944171
TI  - [An expert analysis of diagnostic criteria for traditional Chinese medicine
      syndromes of chronic obstructive pulmonary disease at acute exacerbation stage].
AB  - OBJECTIVE: To investigate the common syndromes, clinical symptoms and
      characteristics of chronic obstructive pulmonary disease at acute exacerbation
      stage (AECOPD). METHODS: Delphi method was used to organize the AECOPD expert
      questionnaire. This questionnaire was distributed to 30 selected experts of
      respiratory diseases. The resulting data were statistically analyzed by Chi
      square test and statistical description such as mean, coefficient of variation
      and ratio of full marks. Common syndrome: mean>=3.00, coefficient of variation
      <30% and ratio of full marks>=10% and common clinical symptoms: for major
      symptoms present, the index mean>=4.00 and coefficient of variation <30% and for
      minor symptom, index mean>=3.00 and coefficient of variation <30% were used as
      criteria. RESULTS: Twenty-nine valid expert questionnaires were received. The
      coefficient of positivity was 96.67%, of authority was 0.835 and of coordination
      equals 0.359 (chi(2)=463.15, P=0.001). The mean, coefficient of variation and
      ratio of full marks for AECOPD syndrome of wind and cold invasion of lung were
      4.12, 21.50%, and 34.48%, respectively. Those for syndrome of exogenous cold-evil
      and fluid-retention were 4.39, 14.32%, 48.28%; those for syndrome of wind and
      heat invasion of lung were 3.54, 30.77%, 6.90%;those for syndrome of phlegm-heat
      obstruction of the lung were 4.85, 9.23%, 89.66%; those for syndrome of pulmonary
      stagnation of phlegm were 4.36, 15.57%, 48.28%; those for syndrome of external
      cold and internal heat were 4.59, 16.27%, 65.52%; those for syndrome of retention
      of phlegm and blood stasis in the lung were 4.54, 12.70%, 55.17%; those for
      syndrome of qi deficiency of the lung and spleen were 3.25, 27.30%, 13.79%; those
      for syndrome of qi deficiency of the lung and kidney were 3.32, 27.24%, 13.79%;
      those for syndrome of qi-yin deficiency of the lung and kidney were 3.29, 28.98%,
      24.14%; those for syndrome of yin deficiency of the lung and kidney were 2.98,
      32.71%, 3.45%; those for syndrome of blood stasis were 4.67, 10.29%, 62.07% and
      those for syndrome of fu shi were 3.07, 30.01%, 6.90%, all respectively. The
      blood stasis and fu shi were accompanying syndromes. CONCLUSION: Seven common
      syndromes of AECOPD are wind and cold invasion of lung, exogenous cold-evil and
      fluid-retention, phlegm-heat obstruction in the lung, pulmonary stagnation of
      phlegm qi deficiency of the lung and spleen, qi deficiency of the lung and
      kidney, as well as qi-yin deficiency of the lung and kidney. One additional
      syndrome that accompanies many of the afore-mentioned syndromes was blood stasis.

PMID- 21944172
TI  - [The change in strategy of mechanical ventilation: a single center study in
      China].
AB  - OBJECTIVE: To observe the treatment strategy and its changes in mechanical
      ventilation (MV) in a single medical center. METHODS: Five hundred and two
      patients undergoing MV for at least 24 hours from January 1994 to December 1997
      (control group) and from January 2004 to December 2006 (study group) in a total
      of 1 090 patients who were admitted to intensive care unit (ICU) Fuxing Hospital,
      Capital Medical University during the 2 periods were investigated. Datas
      including causes for the initiation of MV, ventilator modes and treatment
      parameters, weaning methods, and prognosis of patients were collected. RESULTS:
      The total incidence of MV was 46.1% (502/1 090). The incidence of MV in control
      group was 48.9% (184/376), and that in study group was 44.5% (318/714),
      respectively. The main causes for MV of 502 patients were pneumonia 18.3% (92
      cases), acute exacerbation of chronic obstructive pulmonary disease (AECOPD)
      16.3% (82 cases), postoperation 13.7% (69 cases), coma 14.1% (71 cases) , and
      acute respiratory distress syndrome (ARDS) 12.7% (64 cases). The initial
      ventilator mode: 59.8% (110/184) or 23.0%(73/318) in control or study group was
      assist/control ventilation (A/C), and 57.2% (182/318) or 20.7%(38/184) in study
      or control group was pressure support ventilation (PSV), and there was
      significant difference between the two groups (both P<0.01). The use of
      noninvasive ventilation (NPPV) in study group was obviously increased compared
      with control group [10.4% (33/318) vs. 3.8% (7/184), P<0.01]. The mean pressure
      level of pressure support (PS) of all patients was 14.0 cm H(2)O (1 cm
      H(2)O=0.098 kPa), the mean positive end-expiratory pressure (PEEP) of both groups
      was 5.0 cm H(2)O. Compared with control group, PEEP (cm H(2)O) level in patients
      with ARDS was significantly higher (8.0 vs. 6.0, P<0.01) and volume tidal (V(T),
      ml) was significantly lower (400 vs. 550, P<0.01) in study group. The most
      frequently used weaning methods of both groups were T-piece, T-piece+PSV and PSV.
      The use of T-piece in study group was significantly higher than that in control
      group [84.4% (184/218) vs. 35.1% (40/114), P<0.01], and PSV was lower than that
      in control group [2.8% (6/218) vs. 29.8% (34/114), P<0.01]. The total mortality
      of MV patients in two groups in ICU was 49.6%(249/502). There was no significant
      difference of the mortality between study group and control group (54.6% vs.
      55.4%, P=0.887). CONCLUSION: The ventilator modes and settings had been changed
      in a single medical center in the past 10 years. It is speculated that the
      changes are related with the results observed in some multicenter randomized
      controlled trials (RCTs).

PMID- 21944173
TI  - [Clinical analysis of non-invasive positive pressure ventilation in
      immunocompromised host with acute respiratory failure].
AB  - OBJECTIVE: To evaluate the value of non-invasive positive pressure ventilation
      (NPPV) in immunocompromised host (ICH) complicated by acute respiratory failure
      (ARF), and to investigate predictive variables of success with NPPV in ICH with
      ARF. METHODS: A retrospective study of immunocompromised patients with ARF, who
      were admitted to respiratory intensive care unit (RICU) from March 2008 to March
      2011, was performed. Based on clinical data, univariate Logistic regression was
      done for prediction for independent factors affecting the success of NPPV
      treatment. Immunization status was assessed according to clinical outcome.
      RESULTS: NPPV was instituted in all 33 cases with ARF initially. Among these
      patients, 9 patients (27.3%) received sequential invasive mechanical ventilation
      (IMV, failure group) and all of them died finally; among 24 cases (72.7%) who
      only received NPPV (success group), 7 patients died (29.2%). There was
      significant difference between the two groups in mortality (P<0.01). The
      simplified acute physiology scoreII (SAPSII) in the success group was lower than
      that in the failure group (33+/-9 vs. 43+/-5, P<0.01). However, other clinical
      data showed no statistical significance between two groups. Univariate Logistic
      regression analysis identified SAPSII was the independent factor associated with
      the success of NPPV treatment [odds ratio (OR) =0.83, 95% confidence interval
      (95% CI) 0.709-0.964, P<0.05]. And SAPSII>=38 was a risk factor for the failure
      of NPPV [area under receiver operating characteristic (ROC) curve 0.73]. In
      addition, the lung injury scores (LIS) in the survival group was significantly
      lower than that of the death group (1.95+/-0.48 vs. 2.57+/-0.52, P<0.01), the
      difference was statistically significant. CD3(+) and CD8(+) T counts in the
      survivors were higher than that of non-survivors (CD3(+):0.73+/-0.16 vs. 0.41+/
      0.20; CD8(+): 0.51+/-0.18 vs. 0.21+/-0.15, both P<0.01), and the difference was
      statistically significant. CONCLUSION: As an early treatment for ICH with
      pulmonary infections suffering from ARF, NPPV can be effective for the ICH
      patients suffering from severe pulmonary infection through improving hypoxemia,
      ameliorating respiratory distress symptoms, and avoiding complications associated
      with IMV when SAPSIIis less than 38. CD3(+), CD8(+), and the LIS can be used to
      evaluate the prognosis of those patients.

PMID- 21944174
TI  - [Combined effects of elevated body position on gastroesophageal reflux and intra
      abdominal pressure in mechanical ventilated patients].
AB  - OBJECTIVE: To investigate the combined effects of elevated body position on
      gastroesophageal reflux and intra-abdominal pressure (IAP) in patients undergoing
      mechanical ventilation (MV) who were receiving enteral nutrition, and to find out
      their proper height of head of bed. METHODS: The continuous pH-impedance and
      bladder pressure (reflecting IAP) at different body positions (0 degree angle, 20
      degree angle, 30 degree angle, 45 degree angle) in 6 hours were monitored in 41
      MV and enteral nutrition supported patients. The patients who did not have
      previous gastroesophageal reflux disease (GERD) were admitted to intensive care
      unit (ICU) of Peking University Third Hospital from March 2010 to December 2010
      were included in the study. RESULTS: (1)The most common fluid reflux were weak
      acid and non-acid reflux. Acid reflux was rare. When elevating the body position
      from 0 degree to 30 degree angle, the accumulated numbers of these 3 kinds of
      reflux were declined significantly, and the percentage of high esophageal reflux
      decreased significantly (numbers of reflux: 0 degree angle: 20 degree angle: 30
      degree angle: acid 3.0: 2.0: 1.0, weak acid 13.0: 9.0: 6.0, non-acid 4.0: 3.0:
      2.0; percentage of high esophageal reflux: 0 degree angle: 20 degree angle: 30
      degree angle: acid 16.00%: 9.00%: 7.84%; weak acid 68.40%: 47.40%: 46.69%; non
      acid 15.61%: 9.82%: 8.89%, P<0.05 or P<0.01). But when elevating the body
      position from 30 degree angle to 45 degree angle, no more significant changes in
      the numbers of reflux were found, instead, the percentage of high esophageal
      reflux increased (numbers of reflux 30 degree angle: 45 degree angle: acid 1.0:
      1.0, weak acid 6.0: 5.0, non-acid 2.0: 2.0, all P>0.05; percentage of high
      esophageal reflux 30 degree angle: 45 degree angle: acid 7.84%: 12.00%, weak acid
      46.69%: 52.29%, non-acid 8.89%: 17.58%, all P<0.05).(2) Four of the 41 patients
      (9.76%, 4/41) were found to have intra-abdominal hypertension (IAH) at 0 degree
      angle body position, with one patient at IV degree (IAH>25 mm Hg, 1 mm Hg= 0.133
      kPa). With the patients' body position elevated, the IAP appeared to be further
      increased [the IAP (mm Hg) at 0 degree angle, 20 degree angle, 30 degree angle,
      45 degree position were 10.32+/-3.48, 11.33+/-3.71, 13.55+/-3.58 and 18.25+/
      3.82, respectively P<0.01]; With each level of elevation of the body position,
      the increasing rate was enhanced markedly [the increasing rate of IAP from 0
      degree angle to 20 degree angle, 20 degree angle to 30 degree angle and 30 degree
      to 45 degree were (9.74+/-3.05)%, ( 19.60+/-5.67 )% and (34.73+/-7.67)%,
      respectively, the difference between any two groups was significant, all P<0.01].
      When elevating the body position from 30 degree to 45 degree angle, the numbers
      of patients with different levels of IAH were increased significantly too (30
      degree angle: 45 degree angle: leveI: 5: 8; leveII: 2: 5; level III: 3: 5; level
      IV: 2: 3, P<0.05 or P<0.01). CONCLUSION: Although elevation of the body position
      of MV patients can reduce gastroesophageal reflux, it also increase the IAP. When
      the body position is elevated to 45 degree angle, the number of reflux is not
      reduced effectively, while the rate of high esophageal reflux and the patients'
      IAP are increased significantly, indicating that 30 degree might be the proper
      body position for the MV patients receiving enteral nutrition.

PMID- 21944175
TI  - [The role of hypoxia inducible factor-1alpha and vascular endothelial growth
      factor in hypoxic pulmonary hypertension in patients with acute high altitude
      reaction of rescue workers in Yushu earthquake].
AB  - OBJECTIVE: To assess the effects of hypoxia inducible factor-1alpha (HIF-1alpha)
      and vascular endothelial growth factor (VEGF) on hypoxic pulmonary
      hypertension(HPH) in patients with acute high altitude reaction(AHAR) and its
      change after return to lower altitude. METHODS: Ninety-six officers and soldier
      participating in rescue of Yushu megaseism on April 14th in 2010, leaving low
      altitude area (1 500 m) rapidly to high altitude area(3 700 m) to undertake
      strenuous physical work were enrolled for study. All of them were male, aged 18
      35 years, and they were divided into three groups according to the symptomatic
      scores of AHAR: without AHAR(group B, n=25), mild to moderate AHAR (group C, n=47
      ) and severe AHAR (group D, n=24). Mean pulmonary artery pressure (mPAP), levels
      in serum HIF-1alpha and VEGF were measured at high altitude area after a stay of
      50 days, and also after their return to lower altitude area (1 500 m) for 12
      hours and 15 days. Fifty healthy volunteers at low altitude area served as
      control (group A). RESULTS: Level of mPAP (mm Hg, 1 mm Hg=0.133 kPa), serum HIF
      1alpha (pg/L) and VEGF (ng/L) in group B (24.23+/-1.56, 68.80+/-7.52 and 82.56+/
      6.32) were significantly higher than those in group A (18.50+/-1.30, 50.95+/-3.33
      and 65.78+/-4.03), respectively (all P<0.01). Moreover, the value of all the
      parameters increased with increase in severity of AHAR, the respective value in
      group C were 28.42+/-1.32, 88.10+/-9.20 and 104.82+/-10.36, and in group D were
      34.70+/-2.94, 117.93+/-13.46 and 136.77+/-12.03, and there were significant
      differences in comparing two groups (all P<0.01). At high altitude area, AHAR
      total score was positively correlated with mPAP, serum HIF-1alpha and VEGF
      (r=0.672, 0.737 and 0.634, respectively, all P<0.01), mPAP was positively
      correlated with serum HIF-1alpha and VEGF (r=0.706, 0.638, both P<0.01). Compared
      with group A, level of mPAP (29.08+/-4.22), serum HIF-1alpha (91.16+/-20.58) and
      VEGF (107.11+/-10.32) were significantly increased in 96 officers and soldiers
      who stayed for 50 days at an altitude of 3 700 m (all P<0.01), and the values
      were significantly decreased after returning to lower altitude area for 12
      hours(23.05+/-3.18, 70.99+/-8.22 and 78.65+/-6.47) and 15 days(18.96+/-1.75,
      52.31+/-4.92 and 63.08+/-4.55). The values showed significant difference between
      12 hours and 15 days stay at 1 500 m (all P<0.01). The values of the determined
      parameters 15 days after return to lower altitude area showed no difference
      compared with those of group A (all P>0.05). CONCLUSION: Strenuous physical work
      at high altitude area, AHAR becomes more serious, and it is accompanied by higher
      values of HIF-1alpha, VEGF and mPAP, indicating that HPH is closely associated
      with elevation of HIF-1alpha and VEGF. These changes are improved after returning
      to lower altitude area for 12 hours, and they recover to normal lever after 15
      days.

PMID- 21944176
TI  - [Comparison of sedative effect of dexmedetomidine and midazolam for post
      operative patients undergoing mechanical ventilation in surgical intensive care
      unit].
AB  - OBJECTIVE: To study sedative effect and safety of dexmedetomidine and midazolam
      for post-operative patients undergoing mechanical ventilation(MV) in surgical
      intensive care unit(SICU). METHODS: Two hundred cases of post-operative patients
      undergoing MV with tracheal intubation in SICU were enrolled and divided into two
      groups by random numerical table method. They were treated either with midazolam
      (98 cases) or dexmedetomidine (102 cases). In both groups fentanyl was given
      intravenously continually for analgesia. The amount of fentanyl was adjusted
      according to Prince-Henry analgesic score to keep on 1-2 analgesic score; the
      dose of sedation was regulated by Riker sedative and restless score (SAS)
      maintain 2-4 sedative score. During the course, parameters of the ventilator,
      electrocardiogram, heart rate(HR), blood pressure, respiratory rate, pulse oxygen
      saturation (SpO(2)), blood gas analysis were observed and registered
      continuously. The amount of the drug, duration of MV, and incidence of side
      effects such as hypotension, bradycardia, delirium, nausea, etc. were recorded in
      two groups. RESULTS: In all the patients in two groups taking dexmedetomidine or
      midazolam expected sedative and analgesia scores were obtained. In the group with
      dexmedetomidine, the patients were aroused easier with adequate sedation, and
      when compared with the group with midazolam, dose of fentanyl (MUg* kg(-1)*h(-1)
      ) was significantly smaller (0.23+/-0.13 vs. 0.41+/-0.12, P<0.01), duration of MV
      (hours) was clearly shorter (7.20+/-6.29 vs. 12.44+/-8.96, P<0.01), the rates of
      hypotension (27.45% vs. 11.22%) and bradycardia (24.51% vs. 10.20%) were
      significantly higher (both P<0.05), the rate of delirium was clearly lower (3.92%
      vs. 31.63%, P<0.01), the rate of nausea showed a slight decrease (9.80% vs.
      11.22%, P>0.05). The patients in the group with dexmedetomidine were divided into
      two subgroups of hypotension and non-hypotension. The quantity of blood loss
      during operation (ml/kg), amount of fluid infusion during operation (ml* kg(
      1)*h(-1) ), blood lactic acid concentration (mmol/L) on the day of surgical
      operation and the 1st day post-operative showed no significant difference between
      these subgroups (quantity of blood loss on the day of surgical operation: 12.79+/
      12.13 vs. 13.52+/-11.62; amount of fluid infusion during surgical operation:
      11.91+/-4.59 vs. 13.09+/-7.05;blood lactic acid concentration on the day of
      operation: 1.88+/-1.07 vs. 1.71+/-0.87, blood lactic acid concentration on the
      1st day post-operative:1.43+/-0.98 vs. 1.37+/-0.79, all P>0.05). CONCLUSION:
      Sedative effect of dexmedetomidine is satisfactory for patients undergoing MV
      after operation, with the property of easier arousal, lower delirium rate, and it
      helps to shorten the duration of MV with reduction the dosage of fentanyl by 50%.
      However, it is necessary to enhance observation in order to prevent and control
      hypotension and bradycardia.

PMID- 21944177
TI  - [Effect of angiotensin II on expression of alveolar epithelial sodium channel in
      rat].
AB  - OBJECTIVE: To research the effect of exogenous angiotensin II (AngII) on alveolar
      fluid clearance (AFC) and alveolar epithelial sodium channel (ENaC) expression in
      rats. METHODS: Fifteen healthy Sprague-Dawley (SD) rats were randomly divided
      into control group, AngII group and AngII type 1 (AT1) receptor blocker ZD7155
      pretreatment group, with 5 rats in each group. Exogenous AngII 10 MUg* kg(
      1)*min(-1)was administered by micro pump via catheter in left jugular vein in
      AngII group and ZD7155 pretreatment group, whereas control group rats received
      only normal saline. ZD 7155 10 mg/kg was injected intraperitoneal 30 minutes
      before administration of exogenous AngII in ZD7155 pretreatment group. The
      pathological changes in lung were observed after 6 hours. AFC was estimated by
      Evans-blue labeled 5% albumin. The mRNA and protein expression of ENaC were
      determined by semi-quantitative reverse transcription-polymerase chain reaction
      (RT-PCR) and Western blotting. RESULTS: AFC in AngII group was significantly
      lower than that of control group [(6.16 +/- 3.01)% vs. (16.10 +/- 3.46)%,
      P<0.01], and AFC in ZD7155 pretreatment group was significantly higher than that
      of AngII group [(10.60 +/- 2.05)% vs. (6.16 +/- 3.01)%, P<0.05]. alpha-ENaC mRNA
      expression was significantly increased in AngII group compared with control group
      (0.663 +/- 0.068 vs. 0.236 +/- 0.030, P<0.01), but significantly decreased in
      ZD7155 pretreatment group when compared with AngII group (0.386 +/- 0.061 vs.
      0.663 +/- 0.068, P<0.01). There was no significant difference in beta-ENaC and
      gamma-ENaC mRNA expression among three groups. Compared with control group, alpha
      ENaC protein was significantly increased in AngII group (0.343 +/- 0.053 vs.
      0.145 +/- 0.030, P<0.01), but beta-ENaC and gamma-ENaC proteins were
      significantly decreased (beta-ENaC: 0.286 +/- 0.038 vs. 0.512 +/- 0.055, gamma
      ENaC : 0.144 +/- 0.040 vs. 0.460 +/- 0.066, both P<0.01). Compared with AngII
      group, alpha-ENaC protein was significantly lower(0.228 +/- 0.045 vs.0.343 +/-
      0.053, P<0.01), whereas beta-ENaC and gamma-ENaC proteins were significantly
      higher (beta-ENaC: 0.358 +/- 0.043 vs. 0.286 +/- 0.038, gamma-ENaC: 0.220 +/-
      0.033 vs. 0.144 +/- 0.040, both P<0.05) in ZD7155 pretreatment group. CONCLUSION:
      Exogenous AngII modulates ENaC expression of gene and protein by AT1 receptor
      pathway, attenuates AFC, and aggravates lung edema.

PMID- 21944178
TI  - [Effect of mechanical ventilation guided by transpulmonary pressure on
      hemodynamics and oxygen metabolism of porcine model of intra-abdominal
      hypertension].
AB  - OBJECTIVE: To assess the effect of mechanical ventilation (MV) guided by
      transpulmonary pressure (Ptp) on hemodynamics and oxygen metabolism of porcine
      model of intra-abdominal hypertension (IAH). METHODS: All 6 pigs were
      anesthetized and received MV. Volume-assist control was set: tidal volume (V(T))
      was 10 ml/kg, respiratory rate (RR) was 16 bpm, inhaled oxygen concentration
      (FiO(2)) was 0.40 and positive end-expiratory pressure (PEEP) was set at 5 cm
      H(2)O (1 cm H(2)O=0.098 kPa). Following baseline observations, high intra
      abdominal pressure (IAP) with intraperitoneal nitrogen inflation was induced in
      all 6 pigs. The IAP was increased to 25 mm Hg (1 mm Hg=0.133 kPa). Two hours
      later, PEEP was adjusted to such a level that Ptp during end-expiratory occlusion
      remained at a level above 0 cm H(2)O for 2 hours by measuring esophageal
      pressure, and with the rest parameters of breathing machine remaining constant.
      During the experimental period, hemodynamic parameters including heart rate (HR),
      mean arterial pressure (MAP), cardiac output index (CI), central venous pressure
      (CVP), pulmonary arterial wedge pressure (PAWP), and respiratory mechanics index
      of peak airway pressure (Ppeak), plateau pressure (Pplat), esophageal pressure
      (Pes) and static compliance (Cst) were continuously recorded with the aid of Swan
      Ganz catheter and electrocardiogram. Oxygen partial pressure of arterial blood
      (PaO(2) ) and carbon dioxide partial pressure of arterial blood (PaCO(2)) were
      measured by blood-gas analysis. Systemic oxygen delivery (DO(2) )and systemic
      oxygen consumption(VO(2)  )were calculated according to blood-gas analysis of
      arterial and central venous blood. RESULTS: No porcine model showed barotrauma
      and death. Compared with baseline, at 1 hour and 2 hours after induction of IAH
      in the animals, HR(bpm) increased significantly (134.3+/-5.8, 127.3+/-3.3 vs.
      117.7+/-1.5). MAP(mm Hg), CVP (mm Hg) and PAWP (mm Hg) became higher (MAP:120.7+/
      3.8, 117.3+/-4.8 vs. 100.4+/-6.6; CVP: 7.3+/-0.3, 7.6+/-0.9 vs. 5.6+/-0.2; PAWP:
      14.0+/-0.6, 14.0+/-1.0 vs. 12.3+/-0.3),  CI (L*min(-1)*kg(-1)) was lowered
      (0.150+/-0.019, 0.137+/-0.014 vs. 0.179+/-0.021), Ppeak(cm H(2)O), Pplat (cm
      H(2)O), Pes (cm H(2)O) were increased significantly (Ppeak: 46.3+/-2.3, 47.0+/
      3.2 vs. 11.0+/-1.6; Pplat: 25.7+/-1.3, 26.0+/-1.6 vs. 9.0+/-0.6; Pes: 13.7+/-0.3,
      14.3+/-0.3 vs. 2.3+/-0.3), Cst (ml/cm H(2)O), PaO(2)  (mm Hg) and DO(2)  (ml*min(
      1)*kg(-1)) showed significant lowering (Cst: 8.3+/-0.3, 9.0+/-0.6 vs. 23.0+/-1.6;
      PaO(2) : 142.0+/-13.2, 140.0+/-16.0 vs. 166.3+/-11.3; DO(2) : 19.40+/-2.90, 19.88
      +/-4.14 vs. 25.07+/-6.30, all P<0.05).However, compared to routine ventilation,
      at 1 hour and 2 hours after PEEP had been adjusted according to measurements of
      esophageal pressure, PaO(2) , DO(2)  and Cst increased significantly (PaO(2) :
      161.6+/-11.9, 164.0+/-13.6; DO(2) : 21.90+/-6.21, 21.16+/-2.78; Cst: 12.0+/-1.6,
      12.7+/-2.9). CI became lower (0.121+/-0.013, 0.120+/-0.012)and Pplat was
      higher(31.3+/-3.4, 31.7+/-3.2, all P<0.05). The lactate (mmol/L) was also
      decreased significantly (1.60+/-0.12 vs. 2.70+/-0.44, 1.67+/-0.07 vs. 2.27+/
      0.13, both P<0.05). PaCO(2), HR, MAP, CVP and PAWP showed no significant
      differences compared to IAH pigs ventilated with lower PEEP (all P>0.05).
      CONCLUSION: There were remarkable effects on oxygen metabolism and Cst and less
      influence on hemodynamics in response to MV guided by Ptp. The results of this
      study are in favor of setting Ptp according to measurements of esophageal
      pressure in pigs with IAH.

PMID- 21944179
TI  - [The experiment study of treatment of infectious acute lung injury by intravenous
      administration of adenovirus borne inhibitor of nuclear factor-KappaB gene in
      rat].
AB  - OBJECTIVE: To observe the effects of adenovirus borne IKappaB gene, an inhibitor
      of nuclear factor-KappaB (NF-KappaB), infused via central vein, to treat
      infectious acute lung injury (ALI) in rats. METHODS: According to random number
      table method, 30 pathogen-free Sprague-Dawley (SD) rats were randomly divided
      into three groups: sham group, ALI model group, IKappaB gene treatment group,
      with 10 rats in each group. The rats of IKappaB gene treatment group were infused
      1 ml adenovirus borne IKappaB gene (titre: 1*10(9)pfu  ), the rats of sham group
      and ALI model group were infused 1 ml normal saline through central vein.
      Subsequently, the rats of ALI model group and the IKappaB gene treatment group
      were given 1 ml lipopolysaccharide (LPS, 5 ml/kg) through tail vein to reproduce
      model of ALI. On the other hand, the rats of sham group were given 1 ml normal
      saline through tail vein. Blood gas analysis, the ratio of wet to dry weight
      (W/D) of lung, plasma contents of tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-6 (IL-6), and protein expression of NF-KappaBp65 in lung tissue were
      determined, the pathobiological changes in lung tissue were microscopically
      observed and the scores of lung injury were calculated after 7 days. RESULTS: The
      rats in three groups survived, except 1 rat died in ALI model group.Blood pH and
      partial pressure of arterial carbon dioxide (PaCO(2)) showed no obviously
      differences among three groups. Partial pressure of arterial oxygen (PaO(2) ) was
      highest in sham group and the lowest in ALI model group. The plasma content of
      TNF-alpha (MUg/L) and IL-6 (ng/L ) in ALI model group were obviously higher than
      those in sham group (TNF-alpha: 5.20+/-1.09 vs. 3.01+/-0.46; IL-6: 540.28+/
      100.78 vs. 214.45+/-61.37, both P<0.05). The plasma content of TNF-alpha and IL-6
      in IKappaB gene treatment group were obviously lower than those in ALI model
      group (TNF-alpha: 3.70+/-0.96 vs. 5.20+/-1.09, IL-6: 356.49+/-60.58 vs. 540.28+/
      100.78, both P<0.05), and TNF-alpha content had restored to the level observed in
      sham group. The ratio of W/D of lung was lowest in sham group (4.49+/-0.36) and
      highest in ALI model group (5.78+/-0.43), and that of IKappaB gene treatment
      group (5.33+/-0.38) was lower than that of ALI group. The score of lung injury
      was lowest in sham group (0.17+/-0.41) and highest in ALI model group (2.29+/
      0.76), and that of IKappaB gene treatment group (1.57+/-0.53) was lower than that
      of ALI group. The scale of NF-KappaBp65 immunohistochemistry was lowest in sham
      group (1.00+/-0.89) and highest in ALI model group (9.43+/-1.13), and that of
      IKappaB gene treatment group (4.00+/-1.15) was lower than the latter. The
      differences of all the above parameters in three groups were statistically
      significant (all P<0.05 ). CONCLUSION: Increased expression of IKappaB gene by an
      infusion of adenovirus borne IKappaB gene through central vein can lower the
      levels of pro-inflammatory factors, such as TNF-alpha and IL-6, restrain the NF
      KappaB activation, reduce lung water, alleviate alveolar collapse and lung
      consolidation in ALI in rats, thus lung injury is ameliorated.

PMID- 21944180
TI  - [The efficacy of intermittent pneumatic compression in the prevention of venous
      thromboembolism in medical critically ill patients].
AB  - OBJECTIVE: To evaluate the efficacy of intermittent pneumatic compression (IPC)
      in the prevention of venous thromboembolism (VTE) in medical critically ill
      patients. METHODS: A prospective, randomized, controlled study was conducted. One
      hundred and sixty-two medical critically ill patients were randomly assigned to
      IPC group and control group by random number table after admitted to intensive
      care unit (ICU) from June 2008 to June 2010. Patients under anticoagulation
      medicine therapy were excluded. Patients in the IPC group were treated with IPC
      to prevent VTE after ICU admission. No measures were taken to prevent VTE in the
      control group. The rate of VTE [deep vein thrombosis (DVT) and pulmonary embolism
      (PE)], duration of mechanical ventilation(MV), the length of stay in ICU, rate of
      non-sudden cardiac death and ICU mortality rate and related side-effects of IPC
      were compared during the subsequent 28 days between two groups. RESULTS: Compared
      with control group, IPC group was shown to have a significantly lower rate of DVT
      [3.80%(3/79) vs. 19.28%(16/83), P<0.01], lower rate of PE [0 (0/79) vs.
      9.64%(8/83), P<0.01] and lower rate of non-sudden cardiac death [1.26%(1/79) vs.
      7.23%(6/83), P<0.01]. Compared with control group, duration of MV (days: 8+/-6
      vs. 9+/-8) and length of stay in ICU (days: 9+/-7 vs. 10+/-7) were shorter, and
      the ICU mortality rate of 28 days (24.05% vs. 31.32%) was lower in the IPC group,
      but they were not statistically significant (all P>0.05). No related side-effects
      were found in the IPC group. CONCLUSION: IPC can prevent VTE, and lower the rate
      of non-sudden cardiac death, and it is safe in medical critically ill patients.

PMID- 21944181
TI  - [Seven hundred and twenty-seven cases of acute pulmonary embolism and seasonal
      variation].

PMID- 21944182
TI  - [Analysis of Eisenmenger's syndrome associated with pulmonary artery thrombosis].

PMID- 21944183
TI  - [Clinical advances in non-invasive ventilation and cardiogenic acute pulmonary
      edema].

PMID- 21944184
TI  - Graphene-promoted 3,4,9,10-perylenetetracarboxylic acid nanocomposite as redox
      probe in label-free electrochemical aptasensor.
AB  - Graphene/3,4,9,10-perylenetetracarboxylic acid (GPD) with three-dimensional
      porous structure has been successfully synthesized and served as redox probe to
      construct ultrasensitive electrochemical aptasensor. The GPD nanocomposite shows
      promoted electrochemical redox-activity of 3,4,9,10-perylenetetracarboxylic acid
      (PTCA) with an obvious well-defined cathodic peak from -0.7 to 0 V that never
      been seen from graphene or PTCA, which avoids miscellaneous redox peaks of PTCA
      in electrochemical characterization, offering a novel redox probe for
      electrochemical sensors with highly electrochemical active area and conductivity.
      To the best of our knowledge, this is the first study that utilizes PTCA self
      derived redox-activity as redox probe in electrochemical sensors. Moreover, the
      interesting GPD possesses the advantages of membrane-forming property, providing
      a direct immobilization of redox probes on electrode surface. This simple process
      not only diminishes the conventional fussy immobilization of redox probes on the
      electrode surface, but also reduces the participation of the membrane materials
      that acted as a barrier of the electron propagation in redox probe
      immobilization. With thrombin as a model target, the redox probe-GPD based label
      free electrochemical aptasensor shows a much higher sensitivity (a detection
      range from 0.001 nM to 40 nM with a detection limit of 200 fM) to that of
      analogous aptasensors produced from other redox probes.

PMID- 21944185
TI  - A multi-amplification aptasensor for highly sensitive detection of thrombin based
      on high-quality hollow CoPt nanoparticles decorated graphene.
AB  - In this work, we have successfully demonstrated a facile strategy to incorporate
      high-quality hollow CoPt bimetal alloy nanoparticles (HCoPt) onto reduced
      graphene oxide sheet (HCoPt-RGs). An advanced sandwich-type electrochemical
      aptasensor for thrombin was proposed by using the HCoPt-RGs conjugates as
      secondary label. The formed conjugates provided large surface area for loading
      plentiful redox probe thionine (Thi), horseradish peroxidase (HRP) and secondary
      aptamer (Apt II) with good stability and friendly biocompatibility, indicating
      their superior properties in electroactive mediator enrichment and biomolecule
      immobilization. Furthermore, activated by glutaraldehyde (GA), the chitosan
      hollow CoPt alloy nanoparticle (CS-HCoPt) film can greatly facilitate the capture
      of primary aptamer (Apt I) and dramatically reduce the nonspecific binding.
      Excellent sensitivity was obtained by detecting the conspicuously enhanced
      electrochemical signal of Thi, which was amplified by HCoPt alloy nanoparticles
      and HRP toward the catalytic reduction of H(2)O(2). The aptasensor displayed
      excellent performance for thrombin with a wide linearity in the range from
      1.0*10(-12) to 5.0*10(-8) M and a relatively low detection limit of 3.4*10(-13)
      M. Moreover, the resulted aptasensor also exhibited good specificity, acceptable
      reproducibility and stability, indicating that the present strategy could pave a
      promising way for the wide application of graphene in clinical research.

PMID- 21944186
TI  - Modeling and development of a low frequency contactless dielectrophoresis (cDEP)
      platform to sort cancer cells from dilute whole blood samples.
AB  - Contactless dielectrophoresis (cDEP) devices are a new adaptation of
      dielectrophoresis in which fluid electrodes, isolated from the main microfluidic
      channel by a thin membrane, provide the electric field gradients necessary to
      manipulate cells. This work presents a continuous sorting device which is the
      first cDEP design capable of exploiting the Clausius-Mossotti factor at
      frequencies where it is both positive and negative for mammalian cells.
      Experimental devices are fabricated using a cost effective technique which can
      achieve 50 MUm feature sizes and does not require the use of a cleanroom or
      specialized equipment. An analytical model is developed to evaluate cDEP devices
      as a network of parallel resistor-capacitor pairs. Two theoretical devices are
      presented and evaluated using finite element methods to demonstrate the effect of
      geometry on the development of electric field gradients across a wide frequency
      spectrum. Finally, we present an experimental device capable of continuously
      sorting human leukemia cells from dilute blood samples. This is the first cDEP
      device designed to operate below 100 kHz resulting in successful manipulation of
      human leukemia cells, while in the background red blood cells are unaffected.

PMID- 21944187
TI  - Selective progesterone receptor modulators in reproductive medicine:
      pharmacology, clinical efficacy and safety.
AB  - OBJECTIVE: To discuss the mechanism of action of selective progesterone receptor
      modulators (SPRMs) and summarize the preclinical and clinical efficacy and safety
      data supporting the potential use of these compounds for gynecologic indications.
      DESIGN: Relevant publications from 2005 onward were identified using a PubMed
      search. Additional relevant articles were identified from citations within these
      publications. SETTING: None. PATIENT(S): None. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): None. RESULT(S): Mifepristone was first developed as a
      progesterone receptor antagonist and licensed for pregnancy termination because
      of the unique property of this compound to terminate pregnancy when associated
      with prostaglandins. Then SPRMs were developed, and among those ulipristal
      acetate, an efficient emergency contraceptive. Because SPRMs effectively inhibit
      endometrial proliferation and reduce endometriotic lesions in animal models, this
      suggests a possible role in the treatment of endometriosis in humans. Finally, a
      number of double-blind, randomized, placebo-controlled trials have demonstrated
      the efficacy of asoprisnil, mifepristone, telapristone acetate, and ulipristal
      acetate in reducing leiomyoma and uterine volume, and suppressing bleeding in
      women with uterine fibroids. CONCLUSION(S): Mifepristone in combination with
      prostaglandins has been licensed for pregnancy termination because of its unique
      ability is this area. Ulipristal acetate is available for emergency
      contraception. Several SPRMs hold further promise as an effective medical therapy
      for patients suffering from endometriosis and leiomyoma.

PMID- 21944188
TI  - [Incidence and prognostic value of ischemic heart disease in high risk
      cardiovascular asymptomatic diabetic patients detected by gated myocardial
      perfusion SPECT study].
AB  - AIM: To determine the clinical utility of the gated myocardial perfusion SPECT to
      detect silent ischemia in asymptomatic diabetic patients without previous
      coronary events and to evaluate the prognosis of this population. MATERIAL AND
      METHODS: A retrospective study of 56 asymptomatic diabetics referred for a gated
      myocardial perfusion SPECT for diagnosis of ischemic disease was performed. The
      criteria for ischemia were: mild SDS<4, moderate SDS 4-8, severe SDS>8. A
      multivariable statistical analysis was carried out to identify possible
      predictive variables of an abnormal SPECT. The cardiovascular events were
      recorded up to December-2010. RESULTS: A high proportion of the 56 patients had
      an abnormal perfusion study (46.4%), there being moderate-severe ischemia in
      10.7%, necrosis with ischemia in 5.4% and necrosis in 7.1%. We found no
      statistical differences in the type of stress used (treadmill or dipyridamole).
      The patients had a high combination of cardiovascular risk factors. In the
      multivariate analysis, diabetic nephropathy was the only factor related to an
      abnormal SPECT (p=0.043). The events recorded in the follow-up were: 2 early
      revascularizations, 5 cardiology admissions, 10 non-cardiac related deaths. The
      existence of ischemia in the SPECT was significantly related to the appearance of
      cardiovascular events (p<0.05). CONCLUSION: A gated myocardial perfusion SPECT in
      asymptomatic diabetics with high combination of cardiovascular risk factors
      detects silent ischemia in a significant proportion and this seems to be related
      to future coronary events. Diabetic nephropathy implies a greater likelihood of
      abnormal studies. However, the screening criteria in this population still need
      to be established for better performance and lower cost.

PMID- 21944190
TI  - Meningeal carcinomatosis in a mucosecretory adenocarcinoma of the lung.

PMID- 21944191
TI  - Utility of the PET-CT in the evaluation of early response to treatment in the
      diffuse large B-cell lymphoma. Preliminary results.
AB  - OBJECTIVE: To assess the role of FDG-PET/CT performed after the first cycles of
      chemotherapy in the prediction of response to treatment in patients with diffuse
      large B-cell lymphoma. METHODS: Twenty patients (mean age: 48 years) were
      included, 16 initial staging and 4 relapse. All patients underwent PET/CT at 3
      times: 1) Baseline, 2) After 1-3 cycles of chemotherapy (early response
      assessment), and 3) End of treatment (evaluation of final response). Early PET/CT
      findings were correlated to the end-treatment PET/CT and follow-up. The
      evaluation of the response was established according to the decrease in uptake of
      the lesions (SUVmax). In the early assessment, a good response indicator (GRI)
      was obtained when the lesion disappeared or had more than 50% reduction in
      SUVmax. At the end of the treatment, a complete metabolic response (CMR) was
      determined in negative PET scans. Follow-up was superior to 19 months and final
      outcome was established as progression/relapse or no evidence of disease (NED).
      RESULTS: At the early treatment evaluation, 16/16 patients of initial staging
      (100%) and 2/4 of relapse (50%) achieved GRI. At the end of treatment evaluation,
      14/16 patients of initial staging with GRI achieved CMR and 1/16 PMR: 14 were
      alive with NED in the follow-up while 1 relapsed. In the second group, 2/2
      patients with GRI achieved CMR (100%): 1 continued with NED in the follow-up and
      another relapsed. CONCLUSION: FDG-PET/CT after the first cycles of chemotherapy
      is useful to monitor treatment due to its high negative predictive value (87.5%),
      using it to modify treatment early in the non-responders.

PMID- 21944192
TI  - False positive of intramammary sentinel lymph node in lymphoscintigraphy.

PMID- 21944193
TI  - Trace metal contamination of Beaufort's Dyke, North Channel, Irish Sea: a legacy
      of ordnance disposal.
AB  - Beaufort's Dyke is a disused ordnance disposal ground within the North Channel of
      the Irish Sea. Over 1 million tonnes of ordnance were disposed of in the dyke
      over a 40 year period representing a substantial volume of trace metal pollutants
      introduced to the seabed. Utilising particle transport modelling software we
      simulated the potential transport of metal particles from Beaufort's Dyke over a
      3 month period. This demonstrated that Beaufort's Dyke has the potential to act
      as a source for trace metal contamination to areas beyond the submarine valley.
      Trace metal analysis of sediments from the Dyke and surrounding National Marine
      Monitoring Programme areas demonstrate that the Dyke is not the most contaminated
      site in the region. Particle transport modelling enables the transport pathways
      of trace metal contaminants to be predicted. Implementation of the technique in
      other munitions disposal grounds will provide valuable information for the
      selection of monitoring stations.

PMID- 21944194
TI  - Biological neutralization of chlor-alkali industry wastewater.
AB  - The present work reports biological neutralization of chlor-alkali industrial
      effluent by an alkaliphilic bacterium, isolated from the Gujarat coast, which was
      identified as Enterococcus faecium strain R-5 on the basis of morphological,
      biochemical and partial 16S rRNA gene sequencing. The isolate was capable of
      bringing down the pH of waste water from 12.0 to 7.0 within 3 h in the presence
      of carbon and nitrogen sources, with simultaneous reduction in total dissolved
      solutes (TDS) up to 19-22%. This bacterium produced carboxylic acid, as revealed
      by FT-IR analysis, which facilitated neutralization of alkaline effluent. The
      presence of unconventional raw materials viz. Madhuca indica flowers or sugar
      cane bagasse as carbon and nitrogen sources could effectively neutralize alkaline
      effluent and thus making the bioremediation process economically viable. The time
      required for neutralization varied with size of inoculum. To the best of our
      knowledge, this is the first report on biological neutralization of a chlor
      alkali industrial effluent.

PMID- 21944195
TI  - Vancomycin storage stability in multilayer thin film coatings for on-demand care.
AB  - A rise in drug-resistant bacteria coupled with a decline in the development of
      new classes of antibiotics has increased the need for new local antibiotic
      delivery methods. To address this need, we have previously developed layer-by
      layer assembled films releasing the potent antibiotic, vancomycin, for use as
      coatings for on-demand care. In this work, we explore the potential for practical
      application of these films through an in-depth study of their long term storage
      stability over a wide range of temperatures, including refrigerator, room and
      elevated temperature (4, 25 and 37 degrees C, respectively). Our results indicate
      that the drug-release profiles and minimum inhibitory concentration against
      Staphylococcus aureus of vancomycin released from films stored at these different
      conditions are not affected over a period of 1-6 months. Consequently, these
      films can be used where traditional refrigeration of prepared intravenous
      vancomycin solutions or immediate reconstitution of lyophilized vancomycin is not
      possible. 

PMID- 21944196
TI  - Early onset of changes to the reproductive system of Fasciola hepatica following
      in vivo treatment with triclabendazole.
AB  - Lambs infected with the Cullompton triclabendazole (TCBZ)-susceptible isolate of
      Fasciola hepatica were treated with TCBZ at a dosage of 10mg/kg at 16 weeks post
      infection. Adult flukes were recovered from the liver at 3h, 24h, 48 h and 60 h
      post-treatment (pt). They were processed for histological analysis of the uterus,
      Mehlis' gland, vitellaria, ovary and testis. At 3h pt, the flukes were
      essentially similar to the controls and were producing normal eggs. Egg
      production had ceased by 24h pt. At this time period, the cells of the Mehlis'
      gland showed some evidence of vacuolation, but otherwise were relatively normal.
      A shift in the population of vitelline cells towards mature cells was observed at
      24h pt, and this trend continued at later time-periods. It was accompanied by a
      breakdown of the cells and the presence of apoptotic bodies. Marked changes to
      the ovary were first noted at 48 h pt, as evidenced by vacuolation and the
      presence of apoptotic bodies. Some disruption to the testis was seen at 24h pt,
      with a reduction in the population of spermatogenic cells, the appearance of
      apoptotic bodies and some peripheral vacuolation of the tubules. These
      abnormalities increased in severity with longer time periods pt. The results
      bring forward the time-line of cessation of egg production by 24h, demonstrating
      that this process is affected very rapidly pt.

PMID- 21944197
TI  - Analysis of indoor PM2.5 exposure in Asian countries using time use survey.
AB  - Most household fuels used in Asian countries are solid fuels such as coal and
      biomass (firewood, crop residue and animal dung). The particulate matter (PM),
      CO, NOx and SOx produced through the combustion of these fuels inside the
      residence for cooking and heating has an adverse impact on people's health. PM
      2.5 in particular, consisting of particles with an aerodynamic diameter of 2.5
      MUm or less, penetrates deep into the lungs and causes respiratory system and
      circulatory system diseases and so on. As a result, the World Health Organization
      (WHO) established guideline values for this type of particulate matter in 2005.
      In this study, the authors focused on PM 2.5 and estimated indoor exposure
      concentrations for PM 2.5 in 15 Asian countries. For each environment used for
      cooking, eating, heating and illumination in which people are present temporarily
      (microenvironment), exposure concentrations were estimated for individual cohorts
      categorized according to sex, age and occupation status. To establish the
      residence time in each microenvironment for each of the cohorts, data from time
      use surveys conducted in individual countries were used. China had the highest
      estimate for average exposure concentration in microenvironment used for cooking
      at 427.5 MUg/m3, followed by Nepal, Laos and India at 285.2 MUg/m3, 266.3 MUg/m3
      and 205.7 MUg/m3, respectively. The study found that, in each country, the PM2.5
      exposure concentration was highest for children and unemployed women between the
      ages of 35 and 64. The study also found that the exposure concentration for
      individual cohorts in each country was greatly affected by people's use of time
      indoors. Because differences in individual daily life activities were reflected
      in the use of time and linked to an assessment of exposure to indoor air
      polluting substances, the study enabled detailed assessment of the impact of
      exposure.

PMID- 21944198
TI  - Spatial and temporal distribution of polycyclic aromatic hydrocarbons (PAHs) in
      the atmosphere of Xiamen, China.
AB  - An intensive sampling program was conducted from October 2008 to September 2009
      at the five different environmental sites in Xiamen, Fujian Province, to study
      the spatial and temporal characteristics of Polycyclic Aromatic Hydrocarbons
      (PAHs) in the gaseous and particulate phase, respectively. The PAHs
      concentrations at different sites were quite distinct during four seasons. The
      average concentrations of PAHs in winter were about 8.4 times higher than those
      in spring, and the concentrations of background were 0.56 times lower than those
      of industrial area. In addition, the higher temperature in summer affected the
      particle/gas partitioning of PAHs and led to the higher concentrations of gaseous
      PAHs. Diagnostic ratios of PAHs, which were employed to indicate the primary
      sources of PAHs in Xiamen, showed that the traffic vehicle exhaust was the
      largest contributor and the primary source for PAHs in Xiamen, especially in
      urban area; while the stationary combustion processes, such as petrochemical
      factories and power plants, were mainly responsible for PAHs sources in the
      industrial areas. The health risk of PAHs in the particulate phase was higher
      than those of the gaseous phase at the five sampling sites. The average toxic
      equivalent (BaPeq) of the benzo[a]pyrene values for PAHs were 0.14, 0.32, 1.38
      and 3.59 ng m(-3) in spring, summer, autumn and winter, respectively.
      Furthermore, the results of average BaPeq in all four seasons indicated that the
      health risks of particulate PAHs were higher than those of the gaseous PAHs at
      different sampling sites.

PMID- 21944199
TI  - Multiple effects and uncertainties of emission control policies in China:
      Implications for public health, soil acidification, and global temperature.
AB  - Policies to control emissions of criteria pollutants in China may have
      conflicting impacts on public health, soil acidification, and climate. Two
      scenarios for 2020, a base case without anticipated control measures and a more
      realistic case including such controls, are evaluated to quantify the effects of
      the policies on emissions and resulting environmental outcomes. Large benefits to
      public health can be expected from the controls, attributed mainly to reduced
      emissions of primary PM and gaseous PM precursors, and thus lower ambient
      concentrations of PM2.5. Approximately 4% of all-cause mortality in the country
      can be avoided (95% confidence interval: 1-7%), particularly in eastern and north
      central China, regions with large population densities and high levels of PM2.5.
      Surface ozone levels, however, are estimated to increase in parts of those
      regions, despite NOX reductions. This implies VOC-limited conditions. Even with
      significant reduction of SO2 and NOX emissions, the controls will not
      significantly mitigate risks of soil acidification, judged by the exceedance
      levels of critical load (CL). This is due to the decrease in primary PM
      emissions, with the consequent reduction in deposition of alkaline base cations.
      Compared to 2005, even larger CL exceedances are found for both scenarios in
      2020, implying that PM control may negate any recovery from soil acidification
      due to SO2 reductions. Noting large uncertainties, current polices to control
      emissions of criteria pollutants in China will not reduce climate warming, since
      controlling SO2 emissions also reduces reflective secondary aerosols. Black
      carbon emission is an important source of uncertainty concerning the effects of
      Chinese control policies on global temperature change. Given these conflicts,
      greater consideration should be paid to reconciling varied environmental
      objectives, and emission control strategies should target not only criteria
      pollutants but also species such as VOCs and CO2.

PMID- 21944200
TI  - Biodegradation of sulfamethazine by Trametes versicolor: Removal from sewage
      sludge and identification of intermediate products by UPLC-QqTOF-MS.
AB  - Degradation of the sulfonamide sulfamethazine (SMZ) by the white-rot fungus
      Trametes versicolor was assessed. Elimination was achieved to nearly undetectable
      levels after 20 h in liquid medium when SMZ was added at 9 mg L(-1). Experiments
      with purified laccase and laccase-mediators resulted in almost complete removal.
      On the other hand, inhibition of SMZ degradation was observed when
      piperonilbutoxide, a cytochrome P450-inhibitor, was added to the fungal cultures.
      UPLC-QqTOF-MS analysis allowed the identification and confirmation of 4 different
      SMZ degradation intermediates produced by fungal cultures or purified laccase:
      desulfo-SMZ, N4-formyl-SMZ, N4-hydroxy-SMZ and desamino-SMZ; nonetheless SMZ
      mineralization was not demonstrated with the isotopically labeled sulfamethazine
      phenyl-13C6 after 7 days. Inoculation of T. versicolor to sterilized sewage
      sludge in solid-phase systems showed complete elimination of SMZ and also of
      other sulfonamides (sulfapyridine, sulfathiazole) at real environmental
      concentrations, making this fungus an interesting candidate for further
      remediation research.

PMID- 21944201
TI  - Ecological risk assessment of urban and industrial systems: a review.
AB  - Numerous ecological risk assessment methodologies have been developed over the
      last twenty years around the world for evaluating urban and industrial systems
      and installations, by both the organisations responsible for implementing
      regulations and the scientific community. Although these methodologies share the
      general principle underlying their use, they differ widely with respect to the
      approaches chosen and the resources employed to apply them. Also, they may even
      have different objectives: prior assessment as part of an impact study before
      building a new installation, or retrospective assessment, for example, in view to
      explaining the reasons for an impact recorded or for forecasting additional
      expected impacts. This article provides a synthesis of the different approaches
      used around the world for carrying out each of the major steps common to all
      ecological risk assessment methodologies. The advantages and limitations of these
      different options are discussed in order to provide elements for formulating any
      new methodology adapted to a given scenario. To conclude, perspectives for
      improving the tools required for these methodologies are proposed, and the
      research works to which priority should be given are identified.

PMID- 21944203
TI  - [Transesophageal guidance during a radiofrequency ablation procedure in a
      newborn].

PMID- 21944202
TI  - Molecular monitoring of the microbial dynamics occurring on historical limestone
      buildings during and after the in situ application of different bio-consolidation
      treatments.
AB  - Microbially Induced Carbonate Precipitation is proposed as an environmentally
      friendly method to protect decayed ornamental stone and introduced in the field
      of preservation of Cultural Heritage. Recent conservation studies performed under
      laboratory conditions on non-sterile calcarenite stones have successfully
      reported on the application of a suitable nutritional solution, inoculated and
      non-inoculated with Myxococcus xanthus, as a bioconsolidation treatment.
      Furthermore, this procedure has been applied in situ, very recently, to selected
      historical buildings in Granada, Spain. For the first time, we evaluate the
      efficiency and risks of the in situ application of the above mentioned treatments
      onto two historical buildings in Granada. The evaluation consists of a detailed
      investigation of the micro-biota actively growing during the seven days of the
      treatments--short-term monitoring and of that remaining on the stones after six
      and twelve months of the application--long-term monitoring. A molecular strategy,
      including DNA extraction, PCR amplification of 16S rRNA sequences, construction
      of clone libraries and fingerprinting by DGGE (Denaturing Gradient Gel
      Electrophoresis) analysis followed by sequencing was used to gain insight into
      the microbial diversity present on the differentially treated stones. The
      monitoring of M. xanthus was performed by PCR using species-specific primers.
      Similar dynamics were triggered on both buildings by the application of the
      nutritional solution (inoculated or non-inoculated). 16S rDNA sequencing revealed
      the dominant occurrence of members belonging to the Firmicutes and Proteobacteria
      during the seven days of the treatment, whereas after one year the order
      Bacillales of the phylum Firmicutes was the predominantly detected
      microorganisms. M. xanthus could be detected only during the seven days of the
      treatment. The treatments seem to activate no dangerous microorganisms and
      furthermore, to select the remainder of a homogeneous group of carbonatogenic
      bacteria on the stones after a long period of time.

PMID- 21944204
TI  - The emerging potential of melanized fungi: black yeast between beauty and the
      beast.

PMID- 21944205
TI  - Resistance to UV-B induced DNA damage in extreme-tolerant cryptoendolithic
      Antarctic fungi: detection by PCR assays.
AB  - Cryptoendolithic Antarctic black fungi are adapted to the harshest terrestrial
      conditions as in the ice-free area of the McMurdo Dry Valleys. Recently,
      surviving space simulated conditions proves their bewildering extremotolerance.
      In order to investigate the potential DNA damage and their response after UV-B
      exposition, two strains of Antarctic cryptoendolithic black fungi, Cryomyces
      antarcticus CCFEE 534 and Cryomyces minteri CCFEE 5187, were irradiated at
      different UV-B doses. Since conventional methods cannot be applied to these
      organisms, the effect on the genome was assessed by RAPD and rDNA amplification
      PCR based assays; the results were compared with the responses of Saccharomyces
      pastorianus DBVPG 6283 treated with the same conditions. Results showed that
      template activity was drastically inhibited in S. pastorianus after irradiation.
      Dramatic changes in the RAPD profiles showed after 30 min of exposure while the
      rDNA amplification of SSU, LSU, and ITS portions failed after 30, 60, and 90 min
      of exposure respectively. No alteration was detected in the templates of the
      Antarctic strains where both RAPD profiles and rDNA PCR amplifications were
      unaffected even after 240 min of exposure. The electroferograms of the rDNA
      portions of Cryomyces strains were perfectly readable and conserved whilst the
      analyses revealed a marked alteration in S. pastorianus confirming the high
      resistance of the Antarctic strains to UV-B exposure.

PMID- 21944206
TI  - The effects of gamma radiation, UV and visible light on ATP levels in yeast cells
      depend on cellular melanization.
AB  - Previously we have shown that growth of melanized fungi is stimulated by low
      levels of gamma radiation. The goal of this study was to examine the effects of
      visible light, UV light, and gamma radiation on the energy level (ATP
      concentration) in melanized Cryptococcus neoformans cells. Melanized C.
      neoformans cells as well as non-melanized controls were subjected to visible, UV
      or gamma radiation, and ATP was quantified by measuring the amount of light
      emitted by the ATP-dependent reaction of luciferase with luciferin. We found that
      all three forms of radiation led to a reduction in the ATP levels in melanized C.
      neoformans cells. This points to a universal melanin-related mechanism underlying
      observation of ATP decrease in irradiated melanized cells. In contrast, in non
      melanized cells visible light led to increase in ATP levels; gamma radiation did
      not cause any changes while UV exposure resulted in some ATP decrease, however,
      much less pronounced than in melanized cells.

PMID- 21944207
TI  - Extremophilic yeasts: plasma-membrane fluidity as determinant of stress
      tolerance.
AB  - Our aim was to investigate the response of selected yeasts and yeast-like fungi
      from extreme environments to various temperatures at the level of their plasma
      membranes, in order to elucidate the connections between their plasma-membrane
      fluidity (measured by electron paramagnetic resonance spectroscopy - EPR), growth
      temperature range, stress tolerance, and ecological distribution. Although all
      studied fungi can be considered mesophilic according to their growth temperature
      profiles, their plasma-membrane fluidity indicated otherwise. Arctic yeast
      Rhodosporidium diobovatum could be classified as psychrotolerant due to its
      higher average membrane fluidity. Extremely halotolerant black yeast-like fungus
      Hortaea werneckii isolated from solar salterns, on the other hand, is not adapted
      to low temperature, which is reflected in the higher average rigidity of its
      plasma membrane and as a consequence its inability to grow at temperatures lower
      than 10 degrees C. The plasma membrane of Aureobasidium sp. isolated so far
      exclusively from an Arctic glacier with its intermediate fluidity and high
      fluidity variation at different temperatures may indicate the specialization of
      this yeast-like fungus to the specific glacial environment. Similar behaviour of
      plasma membrane was detected in the reference yeast, non-extremophilic
      Saccharomyces cerevisiae. Its membranes of intermediate fluidity and with high
      fluidity fluctuation at different temperatures may reflect the specialization of
      this yeast to mesophilic environments and prevent its colonization of extreme
      environments. Halotolerant Aureobasidium pullulans from salterns, and Arctic
      Cryptococcus liquefaciens and Rhodotorula mucilaginosa with moderately
      fluctuating plasma membranes of intermediate fluidity are representatives of
      globally distributed generalistic and stress-tolerant species that can thrive in
      a variety of environments. Keeping the membranes stable and flexible is one of
      the necessities for the microorganisms to survive changes in extreme habitats.
      Our data suggest that plasma-membrane fluidity can be used as an indicator of
      fitness for survival in the extreme environments. In addition to the average
      fluidity of plasma membrane, the fluctuation of fluidity is an important
      determinant of stress tolerance: high absolute fluidity fluctuation is tied to
      decreased survival. The fluidity and its variation therefore reflect survival
      strategy and fitness in extreme environments and are good indicators of the
      adaptability of microorganisms.

PMID- 21944208
TI  - Adaptation of the glycerol-3-phosphate dehydrogenase Gpd1 to high salinities in
      the extremely halotolerant Hortaea werneckii and halophilic Wallemia
      ichthyophaga.
AB  - We report the first identification and characterisation of the glycerol-3
      phosphate dehydrogenase (GPD) genes from extremely halophilic fungi. The black
      ascomycetous yeast Hortaea werneckii and the non-melanised basidiomycetous fungus
      Wallemia ichthyophaga inhabit similar hypersaline environments, yet they have two
      different strategies of haloadaptation through Gpd1-regulated glycerol synthesis.
      The extremely halotolerant H. werneckii codes for two salt-inducible GPD1 genes
      that show similar gene transcription regulation and have 98% amino-acid sequence
      identity between paralogues; however, they have distinct effects when expressed
      heterologously in Saccharomyces cerevisiae gpd mutants. Only the HwGpd1B isoform
      complements the function of Gpd in the gpd1 mutant, whereas none of the Gpd1
      isoforms can rescue the salt sensitivity of the gpd1gpd2 double mutant. The
      obligate halophile W. ichthyophaga codes for only one GPD1 orthologue, the
      transcription of which is less affected by salt when compared to the H. werneckii
      homologues. Heterologous expression of WiGPD1 in S. cerevisiae recovers
      halotolerance of the gpd1 and gpd1gpd2 mutant strains, which is probably due to
      the overall high amino-acid similarity of the Gpd1 protein in W. ichthyophaga and
      S. cerevisiae. Phylogenetic analysis of amino-acid sequences reveals that the
      evolutionary origins of all of these three novel enzymes correspond to the
      phylogeny of the fungal species from which the genes were identified.

PMID- 21944209
TI  - Sample preparation and 2-DE procedure for protein expression profiling of black
      microcolonial fungi.
AB  - The ecology and stress adaptation of black rock inhabiting fungi in hot and cold
      extreme environments are not yet well understood. Two-dimensional gel
      electrophoresis (2-DE) is a promising tool to study the protein expression
      profiling and the metabolic status of microorganisms under stress conditions. The
      sample preparation has been shown to be the bottleneck for high resolution
      protein separation in 2-DE. For this purpose conditions must be optimized to
      obtain reliable and reproducible results. In addition, due to a multilayered and
      strongly melanized cell wall of black microcolonial fungi, special protocols for
      cell disruption and processing are required. In the present study, the protocol
      for protein extraction was established and optimized for the black yeast
      Exophiala jeanselmei MA 2853. The same protocol was successfully examined also
      for the meristematic fungus Coniosporium perforans MA 1299. Among the three
      procedures evaluated, trichloroacetic acid (TCA) precipitation, TCA/acetone
      precipitation, and phenol extraction combined with methanol/ammonium acetate
      precipitation, the latter showed to be the best method for black yeasts and
      meristematic fungi. Penicillium chrysogenum was used as reference strain.

PMID- 21944210
TI  - Black fungi and associated bacterial communities in the phyllosphere of
      grapevine.
AB  - In this study we investigate bacterial communities in association with an
      enriched black-fungal community in the plant phyllosphere to test whether these
      fungi create an environment for specific bacteria. Under organic conditions of
      agriculture, grapevine plants (Vitis vinifera) display an increased occurrence of
      the black fungi Aureobasidium pullulans and Epicoccum nigrum. Their enrichment
      agrees with the tolerance of these fungi to copper and sulphate, both used as
      main fungicides in organic viticulture. Both fungi also intrude the plant
      material to grow endophytically. Bacterial communities associated with black
      fungi of the plant surface and endosphere showed no differences compared to those
      found in conventionally managed V. vinifera plants. This suggests that despite an
      increase of these black fungi in organic practice, they do not shape bacterial
      diversity in grapevine plants. Nevertheless, dual cultures revealed a negative
      effect of Aureobasidium on the growth of certain bacilli, whereas growth of
      Aureobasidium was impeded by one Pseudomonas strain. Such singular effects are
      either not apparent in the natural black-fungal--bacterial community of the grape
      phyllosphere or are of rather localized effect.

PMID- 21944211
TI  - Rock-inhabiting fungi originated during periods of dry climate in the late
      Devonian and middle Triassic.
AB  - Non-lichenized rock-inhabiting fungi (RIF) are slow-growing melanized ascomycetes
      colonizing rock surfaces in arid environments. They possess adaptations, which
      allow them to tolerate extreme abiotic conditions, such as high UV radiations and
      extreme temperatures. They belong to two separate lineages, one consisting in the
      sister classes Dothideomycetes and Arthoniomycetes (Dothideomyceta), and the
      other consisting in the order Chaetothyriales (Eurotiomycetes). Because RIF often
      form early diverging groups in Chaetothyriales and Dothideomyceta, the ancestors
      of these two lineages were suggested to most likely be rock-inhabitants. The
      lineage of RIF related to the Chaetothyriales shows a much narrower phylogenetic
      spectrum than the lineage of RIF related to Dothideomyceta, suggesting a much
      more ancient origin for the latter. Our study aims at investigating the times of
      origin of RIF using a relaxed clock model and several fossil and secondary
      calibrations. Our results show that the RIF in Dothideomyceta evolved in the late
      Devonian, much earlier than the RIF in Chaetothyriales, which originated in the
      middle Triassic. The origin of the chaetothyrialean RIF correlates well with a
      period of recovery after the Permian-Triassic mass extinction and an expansion of
      arid landmasses. The period preceding the diversification of the RIF related to
      Dothideomyceta (Silurian--Devonian) is also characterized by large arid
      landmasses, but temperatures were much cooler than during the Triassic. The
      paleoclimate record provides a good explanation for the diversification of fungi
      subjected to abiotic stresses and adapted to life on rock surfaces in nutrient
      poor habitats.

PMID- 21944212
TI  - Dishwashers--a man-made ecological niche accommodating human opportunistic fungal
      pathogens.
AB  - Habitats in human households may accommodate microorganisms outside the common
      spectrum of ubiquitous saprobes. Enrichment of fungi that may require specific
      environmental conditions was observed in dishwashers, 189 of which were sampled
      in private homes of 101 towns or communities. One-hundred-two were sampled from
      various localities in Slovenia; 42 from other European countries; 13 and 3 from
      North and South America, respectively; 5 from Israel; 10 from South Africa; 7
      from Far East Asia; and 7 from Australia. Isolation was performed on samples
      incubated at 37 degrees C. Species belonging to genera Aspergillus, Candida,
      Magnusiomyces, Fusarium, Penicillium and Rhodotorula were found occasionally,
      while the black yeasts Exophiala dermatitidis and Exophiala phaeomuriformis
      (Chaetothyriales) were persistently and most frequently isolated. Sixty-two
      percent of the dishwashers were positive for fungi, and 56% of these accommodated
      Exophiala. Both Exophiala species are known to be able to cause systemic disease
      in humans and frequently colonize the lungs of patients with cystic fibrosis. We
      conclude that high temperature, high moisture and alkaline pH values typically
      occurring in dishwashers can provide an alternative habitat for species also
      known to be pathogenic to humans.

PMID- 21944213
TI  - Evolution of fungal pathogens in domestic environments?
AB  - Specific indoor environments select for certain stress-tolerant fungi and can
      drive their evolution towards acquiring medically important traits. Here we
      review the current knowledge in this area of research, focussing on the so-called
      black yeasts. Many of these melanised stress-tolerant organisms originate in
      unusual ecological niches in nature, and they have a number of preadaptations
      that make them particularly suited for growth on human-made surfaces and
      substrates. Several pathogenic species have been isolated recently from various
      domestic habitats. We argue that in addition to enriching for - potentially -
      pathogenic species, the selection pressure and stress acting on microorganisms in
      indoor environments are driving their evolution towards acquiring the missing
      virulence factors and further enhancing their stress tolerance and pathogenic
      potential. Some of the polyextremotolerant fungi are particularly problematic:
      they can grow at elevated temperatures, and so they have a higher potential to
      colonise warm-blooded organisms. As several species of black fungi are already
      implicated in health problems of various kinds, their selection and possible
      evolution in human environments are of concern.

PMID- 21944214
TI  - Cladophialophora psammophila, a novel species of Chaetothyriales with a potential
      use in the bioremediation of volatile aromatic hydrocarbons.
AB  - Cladophialophora is a genus of asexual black yeast-like fungi with one-celled,
      hydrophobic conidia which is predicted to have teleomorphs in the ascomycete
      genus Capronia, a member of the order Chaetothyriales. Cladophialophora species
      are relatively frequently involved in human disease ranging from mild cutaneous
      lesions to cerebral abscesses. Although the natural niche outside humans is
      unknown for most opportunistic Cladophialophora species, the fungi concerned are
      rarely isolated from environmental samples such as dead plant material, rotten
      wood, or soil. The objective of the present paper is to describe a novel species
      of Cladophialophora which was isolated from soil polluted with benzene, toluene,
      ethylbenzene, and xylene (BTEX). It proved to be able to grow with toluene and
      other related alkylbenzenes as its sole carbon and energy source. This strain is
      of interest for the biodegradation of toluene and other related xenobiotics under
      growth limiting conditions, particularly in air biofilters, dry and/or acidic
      soil. A preliminary genetic analysis using multilocus sequencing typing (MLST)
      and amplified fragments length polymorphism (AFLP) showed that this fungus was
      closely related to the pathogenic species Cladophialophora bantiana, sharing a C.
      bantiana-specific intron in SSU rDNA. However, it was unable to grow at 40
      degrees C and proved to be non-virulent in mice. The clear phylogenetic and
      ecophysiological delimitation of the species is fundamental to prevent biohazard
      in engineered bioremediation applications.

PMID- 21944215
TI  - Exophiala sideris, a novel black yeast isolated from environments polluted with
      toxic alkyl benzenes and arsenic.
AB  - A novel species of the black yeast genus Exophiala (order Chaetothyriales) is
      described. Strains were repeatedly obtained by enriching samples of wild berries
      from different plants, guano-rich soil and from oak railway ties treated with
      arsenic creosote under a toluene-rich atmosphere. An identical strain was
      encountered in a closed arsenic mine polluted by alkyl benzenes. Its potential
      use for purposes of bioremediation is discussed.

PMID- 21944216
TI  - Use of ribosomal introns as new markers of genetic diversity in Exophiala
      dermatitidis.
AB  - Exophiala dermatitidis is one of the prevalent black yeasts found as
      opportunistic pathogens or colonizers in humans. In the tropics its natural
      habitat is thought to be fruit surfaces and it is also found in the digestive
      system of fruit-eating animals. However, it has recently been abundantly isolated
      from human-made environments (steam baths, railway ties, dishwashers) in tropical
      and temperate climates. Two genotypes have been distinguished within this
      species: genotype A, mostly corresponding to strains isolated from patients, and
      genotype B, to strains isolated from the natural environment. In human-made
      environments, both genotypes A and B occur. A previous study suggested that one
      genotype had been selected for in the human host. In our study, the distribution
      of ribosomal insertions agrees with an ecological specialization of E.
      dermatitidis genotypes by showing a significantly higher frequency of ribosomal
      insertions in clinical strains in comparison to environmental ones. The
      characterization of these insertions shows that they correspond to introns of
      group IC or IE, the most frequent types within the fungal kingdom. These
      ribosomal group I introns could be used as new markers for populations of E.
      dermatitidis.

PMID- 21944217
TI  - Elucidation of distribution patterns and possible infection routes of the
      neurotropic black yeast Exophiala dermatitidis using AFLP.
AB  - Distribution of populations of the opportunistic black yeast Exophiala
      dermatitidis was studied using AFLP. This fungus has been hypothesized to have a
      natural habitat in association with frugivorous birds and bats in the tropical
      rain forest, and to emerge in the human-dominated environment, where it
      occasionally causes human pulmonary or fatal disseminated and neurotropic
      disease. The hypothesis of its natural niche was investigated by comparing a set
      of 178 strains from natural and human-dominated environments in Thailand with a
      worldwide selection of 107 strains from the reference collection of the CBS
      Fungal Biodiversity Centre, comprising 75.7% clinical isolates. Many isolates had
      unique AFLP patterns and were too remote for confident comparison. Eight
      populations containing multiple isolates could be distinguished, enabling
      determination of geographic distributions of these populations. Some of the
      populations were confined to Thailand, while others occurred worldwide. The local
      populations from Thailand contained strains from natural and urban environments,
      suggesting an environmental jump of the fungus. Strains from human brain belonged
      to widely dispersed populations. In some cases cerebral isolates were identical
      to isolates from the human intestinal tract. The possibility of cerebral
      infection through intestinal translocation was thus not excluded.

PMID- 21944218
TI  - Fonsecaea multimorphosa sp. nov, a new species of Chaetothyriales isolated from a
      feline cerebral abscess.
AB  - A novel fungal species is described originating from the left occipital lobe of
      the cerebrum of an 18-month-old spayed female cat in Australia. Neurological
      disorder of the animal became apparent by circling movements and uncoordinated
      behaviour. Sequencing of the SSU rRNA gene reveals this strain as belonging to
      the genus Fonsecaea in Chaetothyriales. This order includes many black yeasts and
      relatives known as etiologic agents of disease in humans and animals, including
      several neurotropic species. Novelty of the species was corroborated by
      morphology and by multilocus sequencing of the ribosomal internal transcribed
      spacers (ITS) and partial sequences of the beta-tubulin (BT2) and translation
      elongation factor (TEF1) genes. The strain is very similar to several strains
      recovered by a selective isolation technique from the natural environment in
      Brazil.

PMID- 21944219
TI  - The diversity of ant-associated black yeasts: insights into a newly discovered
      world of symbiotic interactions.
AB  - Based on pure culture studies and DNA phylogenetic analyses, black yeasts
      (Chaetothyriales, Ascomycota) are shown to be widely distributed and important
      components of numerous plant-ant-fungus networks, independently acquired by
      several ant lineages in the Old and New World. Data from ITS and LSU nu rDNA
      demonstrate that a high biodiversity of fungal species is involved. There are two
      common ant-fungus symbioses involving black yeasts: (1) on the carton walls of
      ant nests and galleries, and (2) the fungal mats growing within non-pathogenic
      naturally hollow structures (so-called domatia) provided by myrmecophytic plants
      as nesting space for ants (ant-plant symbiosis). Most carton- and domatia
      inhabiting fungi stem from different phylogenetic lineages within
      Chaetothyriales, and almost all of the fungi isolated are still undescribed.
      Despite being closely related, carton and domatia fungi are shown to differ
      markedly in their morphology and ecology, indicating that they play different
      roles in these associations. The carton fungi appear to improve the stability of
      the carton, and several species are commonly observed to co-occur on the same
      carton. Carton fungi commonly have dark-walled monilioid hyphae, colouring the
      carton blackish and apparently preventing other fungi from invading the carton.
      Despite the simultaneous presence of usually several species of fungi, forming
      complex associations on the carton, little overlap is observed between carton
      fungi from different ant species, even those that co-occur in nature, indicating
      at least some host specificity of fungi. Most fungi present on carton belong to
      Chaetothyriales, but in a few samples, Capnodiales are also an important
      component. Carton fungi are difficult to assign to anamorph genera, as most lack
      conidiation. The domatia fungi are more specific. In domatia, usually only one or
      two fungal species co-occur, producing a dense layer on living host plant tissue
      in domatia. They have hyaline or light brown thin-walled hyphae, and are commonly
      sporulating. In both carton and domatia, the fungal species seem to be specific
      to each ant-plant symbiosis. Representative examples of carton and domatia ant
      fungus symbioses are illustrated. We discuss hypotheses on the ecological
      significance of the Chaetothyriales associated with ants.

PMID- 21944220
TI  - A non-inflammatory form of immune competence prevails in acute pre-pubescent
      malnutrition: new evidence based on critical mRNA transcripts in the mouse.
AB  - The declining inflammatory immune competence of acute (i.e. wasting) pre
      pubescent protein-energy malnutrition has been regarded as reflecting an
      unregulated immunological disintegration. Recent evidence, however, suggests that
      malnutrition stimulates a regulated immunological reconfiguration to achieve a
      non-inflammatory form of competence, perhaps offering protection against
      autoimmune reactions - the 'Tolerance Model'. Our objective was to determine the
      influence of acute pre-pubescent malnutrition on the expression of genes critical
      to tolerogenic regulation. Male and female C57BL/6J mice, initially 19 d old,
      consumed a complete purified diet either ad libitum (age-matched controls) or in
      restricted daily quantities (mimicking marasmus), or consumed an isoenergetic low
      protein diet ad libitum (mimicking incipient kwashiorkor) for 14 d (six animals
      per dietary group). Gene expression in the spleen, typically an inflammatory
      organ, and in the small intestine, a site designed for non-inflammatory defence,
      was assessed by real-time quantitative RT-PCR, and normalised to beta-actin. In
      the spleen of the malnourished groups, both IL-10 and transforming growth factor
      beta1 mRNA expression increased compared with controls (P < 0.05), whereas mRNA
      expression of IL-12p40 decreased (P < 0.05). Conversely, malnutrition exerted no
      influence on the expression of mRNA for these cytokines in the small intestine
      (P>0.05). Moreover, forkhead box P3 mRNA expression, indicative of cell-based
      tolerogenic potential, was sustained in both the spleen and intestine of the
      malnourished groups (P>0.05). Thus, despite limited supplies of energy and
      substrates, the spleen shifted towards a non-inflammatory character and the
      intestine was sustained in this mode in advanced pre-pubescent weight loss. These
      findings provide the first support for the Tolerance Model at the level of mRNA
      transcript expression.

PMID- 21944221
TI  - Preoperative screening strategies for bacterial vaginosis prior to elective
      hysterectomy: a cost comparison study.
AB  - OBJECTIVE: The purpose of this study is to compare costs of 3 strategies for
      women undergoing hysterectomy: (1) test all patients for bacterial vaginosis;
      treat if positive; (2) treat all patients for bacterial vaginosis; (3) neither
      test nor treat patients for bacterial vaginosis. For comparison purposes, a
      fourth strategy is examined: (4) no surgical site infection prophylaxis or
      bacterial vaginosis treatment. STUDY DESIGN: A cost minimization model was
      created using estimates obtained from the published literature, Medicare
      reimbursement data, and wholesale drug costs. RESULTS: In the base case, the
      optimal strategy was to treat all patients for bacterial vaginosis, with a cuff
      infection rate of 4.0% and mean cost of $593. The "test all patients for
      bacterial vaginosis; treat if positive" strategy was also inexpensive, with a
      mean cost of $623 and 4.2% cuff infection rate. "Neither test nor treat patients
      for bacterial vaginosis" and "no surgical site infection prophylaxis or bacterial
      vaginosis treatment" were more expensive and less effective than other
      strategies. CONCLUSION: This model suggests that consideration should be given to
      adding metronidazole to standard surgical site infection prophylaxis before
      hysterectomy.

PMID- 21944222
TI  - Impact of long-acting reversible contraception on return for repeat abortion.
AB  - OBJECTIVE: The objective of the study was to determine the rate of return for
      repeat abortion in relation to postabortion contraceptive method choice 24 months
      onward from an intervention study. STUDY DESIGN: This was a prospective cohort
      study involving a hospital note search for 510 women 24 months after an abortion.
      RESULTS: Women using long-acting reversible contraceptive (LARC) methods
      (intrauterine device [IUD] and depot medroxyprogesterone acetate) had
      significantly lower return rates for repeat abortion (6.45%; 95% confidence
      interval [CI], 4.0-9.8) than non-LARC users, of whom 14.5% returned (95% CI, 9.9
      20.2). A Cox proportional hazard analysis showed that the postabortion method
      choice was significantly related to the likelihood of returning for a repeat
      abortion (P = .002), controlling for major demographic factors and previous
      pregnancy history. Using the pill as a reference group for risk of repeat
      abortion, the IUD hazard ratio (HR) was 0.36 (95% CI, 0.17-0.77), the depot
      medroxyprogesterone acetate HR was 0.55 (95% CI, 0.21-1.45), and the HR for all
      other methods was 1.8 (95% CI, 0.83-3.92). CONCLUSION: This study provides strong
      support for the promotion of immediate postabortion access to LARC methods
      (particularly intrauterine devices) to prevent repeat abortion.

PMID- 21944223
TI  - Ten-year follow-up after the tension-free vaginal tape procedure.
AB  - OBJECTIVE: The current study aimed to evaluate objective and subjective results
      10 years after the tension-free vaginal tape procedure. STUDY DESIGN: Two hundred
      ten patients who underwent a tension-free vaginal tape procedure at the 2
      participating units between 1999 and 2001 were invited for follow-up. Evaluation
      at 10 years included history, clinical examination, cystoscopy, urodynamics, a
      cough stress test, and the Incontinence Outcome Questionnaire. RESULTS: Interview
      data were available for 67%; full clinical investigation was performed in 56% of
      patients. At 10 years, the clinical stress test was negative in 84%, slightly
      positive in 8.5%, and strongly positive in 4.3%. Subjectively, 57% of patients
      considered themselves "cured," 23% "improved," 6.4% "unchanged," and 11% "worse."
      Eleven of 141 (7.8%) had been reoperated in the interim. The rate of de novo
      urgency was 20%. Obesity seemed to be a risk factor for failure. CONCLUSION:
      These data indicate satisfactory objective and subjective cure rates 10 years
      after tension-free vaginal tape procedure placement.

PMID- 21944224
TI  - The quantitative lung index (QLI): a gestational age-independent sonographic
      predictor of fetal lung growth.
AB  - OBJECTIVE: We sought to develop a gestational age-independent sonographic
      parameter to characterize lung growth. STUDY DESIGN: Reported descriptors of lung
      growth, including lung-to-head circumference (HC) ratio (LHR) and
      observed/expected LHR, were examined. A new index, the quantitative lung index
      (QLI) was derived using published data on HC and the area of the base of the
      right lung. RESULTS: Neither the LHR nor the observed/expected LHR proved to be
      gestational age independent. Right lung growth can be expressed using the
      following formula: QLI = lung area/(HC/10)^2. The 50th percentile of the QLI
      remained constant at approximately 1.0 for the gestational age between 16-32
      weeks. A small lung (<1st percentile) was defined as a QLI <0.6. CONCLUSION:
      Fetal right lung growth can be adequately described using the QLI, independent of
      gestational age. Further studies are needed to assess the clinical accuracy of
      the QLI in characterizing fetal right lung growth.

PMID- 21944225
TI  - Antithyroid antibodies and parity: further evidence for microchimerism in
      autoimmune thyroid disease.
AB  - OBJECTIVE: Fetal microchimerism may have a role in development of autoimmune
      thyroid disorders. Using parity as a surrogate for increasing fetal cell
      exposure, we analyzed its association with thyroid peroxidase antibody levels.
      STUDY DESIGN: Secondary analysis of serum thyroid analytes determined in 17,298
      women from a population-based prospective study between 2001 and 2003. Sera were
      assayed for thyrotropin, free thyroxine, and antithyroid peroxidase antibodies.
      We analyzed the relationship between thyroid peroxidase antibodies and increasing
      parity. RESULTS: The incidence of abnormally elevated thyroid peroxidase antibody
      levels (>50 IU/mL) increased with advancing parity, but was not significant after
      adjustment for maternal characteristics. However, at higher thyroid peroxidase
      antibody levels (>500 IU/mL), a significant relationship with advancing parity
      persisted after adjustments (P = .002). CONCLUSION: Advancing parity is
      associated with an increased risk for high serum concentrations of antithyroid
      peroxidase antibodies. This suggests fetal microchimerism may play a role in
      development of autoimmune thyroid disorders.

PMID- 21944226
TI  - The ATHENA human papillomavirus study: design, methods, and baseline results.
AB  - OBJECTIVE: The objective of the study was to describe baseline data from
      Addressing the Need for Advanced HPV Diagnostics, a prospective, multicenter US
      cervical cancer screening trial. STUDY DESIGN: A total of 47,208 women aged 21
      years or older undergoing routine screening were enrolled; liquid-based cytology
      and human papillomavirus (HPV) testing were performed. Women with abnormal
      cytology underwent colposcopy, as did high-risk HPV (hrHPV)-positive women and a
      random subset of women negative by both tests aged 25 years or older.
      Verification bias adjustment was applied; 95% confidence intervals were computed
      by the bootstrap method. RESULTS: The prevalence of cytologic abnormalities was
      7.1%. hrHPV, HPV 16, and HPV 18 were detected using the cobas HPV Test in 12.6%,
      2.8%, and 1.0% of women, respectively. Both cytologic abnormalities and hrHPV
      positivity declined with increasing age. The adjusted prevalence of cervical
      intraepithelial neoplasia grade 2 (CIN2) or greater in women aged 25-34 years was
      2.3%, decreasing to 1.5% among older women. CONCLUSION: The Addressing the Need
      for Advanced HPV Diagnostics study provides important estimates of the prevalence
      of cytologic abnormalities, hrHPV positivity, and CIN2 or greater in a US
      screening population.

PMID- 21944227
TI  - How the brain responds to any: an MEG study.
AB  - The word any may appear in some sentences, but not in others. For example, any is
      permitted in sentences that contain the word nobody, as in Nobody ate any fruit.
      However, in a minimally different context any seems strikingly anomalous:
      (*)Everybody ate any fruit. The aim of the present study was to investigate how
      the brain responds to the word any in such minimally different contexts - where
      it is permitted (licensed) and where it is not permitted (unlicensed). Brain
      responses were measured from adult readers using magnetoencephalography (MEG).
      The results showed significantly larger responses to permissible contexts in the
      left posterior temporal areas between 400-500 ms and 590-660 ms. These results
      clarify the anatomy and timing of brain processes that contribute to our judgment
      that a word such as any is or is not permitted in a given context.

PMID- 21944228
TI  - [An unusual cause of rectal bleeding in our environment: intestinal
      schistosomiasis].

PMID- 21944229
TI  - [Chronic polyps in the stomach and jejunum in a patient with familial adenomatous
      polyposis].
AB  - The management of extracolonic gastrointestinal polyps is controversial in
      patients with familial adenomatous polyposis (FAP). The treatment of adenomatous
      polyps with severe dysplasia in the stomach through wide gastric resections can
      hamper subsequent surveillance of the development of new polyps in the duodenal
      jejunal area. We report the exceptional case of a 45-year-old man with FAP who
      developed two synchronic adenomatous polyps, with severe dysplasia. The first was
      located in the gastric antrum and the second in the proximal jejunum. Given the
      preoperative diagnosis of gastric neoplasm with invasion of the gastric wall
      (T(2)N(0)), subtotal Roux-en-Y gastrectomy and resection of the proximal jejunal
      segment were performed.

PMID- 21944230
TI  - [Physiopathological bases for the use of human albumin in liver cirrhosis].

PMID- 21944232
TI  - [Interventional radiology in oncology].

PMID- 21944231
TI  - [Elastography in the evaluation of chronic pancreatitis].
AB  - Endoscopic ultrasound (EUS) has become an essential tool in the evaluation of
      pancreatic disease and can be considered the technique of choice for the
      diagnosis and staging of chronic pancreatitis (CP) and pancreatic cancer (PC).
      However, EUS has certain limitations, especially in the evaluation of patients
      with solid pancreatic masses (in the differential diagnosis of CP and PC).
      Furthermore there is variability in the EUS diagnostic criteria for CP. EUS
      guided elastography is emerging as a highly useful tool in this setting. This
      modality has shown high diagnostic accuracy in the differential diagnosis of
      solid pancreatic masses, including differentiation between CP and PC. EUS-guided
      elastography has also been found to be useful in the diagnosis of CP, and can
      even classify patients according to the severity of their disease.

PMID- 21944233
TI  - [Interventional radiology in oncology: inventory].
AB  - A recent survey has compiled an inventory as complete as possible of the
      activities of interventional radiology in oncology in France. This overview has
      focused on identifying all invasive medical procedures whose aim was diagnosis
      and/or treatment of a tumor, which was carried out under guidance and under the
      control of an imaging means (RX, ultrasound, CT, MRI). If the biopsies represent
      more than half of the actions carried out under controlled imaging, recent years
      have seen the development of increasingly powerful therapeutic techniques.

PMID- 21944234
TI  - [Interventional radiology in oncology in private practice].
AB  - Interventional oncology in private practice requires expert training and can be
      performed in a stand-alone facility for type 1 procedures in a hospital setting
      for type 2 and 3 procedures where subspecialized radiologists, state-of-the-art
      equipment, and postprocedure hospital monitoring are available. A
      multidisciplinary effort with oncologists, internal medicine physicians and
      anesthesiologists is necessary. The practice of interventional oncology requires
      around the clock availability, meticulous and established protocols and
      procedures and a financial investment. On the other hand, it is professionally
      gratifying because of constant technical advances and the impact on patients.

PMID- 21944235
TI  - [Percutaneous radiofrequency and other liver ablation techniques: 2011 update].
AB  - Percutaneous ablation of liver tumors was initially limited to patients that were
      not surgical candidates and with a limited number of relatively small liver
      lesions. Because of the diversification of techniques and technologies,
      percutaneous liver ablation has progressively been integrating to more and more
      complex therapeutic strategies available to a wider group of patients. Local
      knowledge and expertise with these techniques, largely dominated by
      radiofrequency ablation, often dictate the role of these techniques in the
      management of patients with liver tumors. We will review the clinical indications
      of percutaneous ablation techniques for liver tumors based on clinical
      considerations as well as ablation techniques.

PMID- 21944236
TI  - [Percutaneous ablation of renal tumors: radiofrequency ablation or
      cryoablation?].
AB  - Percutaneous ablation of renal tumors, including radiofrequency ablation and
      cryoablation, are increasingly being used for small tumors as an alternative to
      surgery for poor surgical candidates. Compared to radiofrequency ablation,
      cryoablation has several advantages: improved volume control and preservation of
      adjacent structures due to the excellent depiction of the ice ball on CT and MRI;
      better protection of the collecting system for central tumor with reduced risk of
      postprocedural urinary fistula. The main pitfall of cryoablation is the higher
      cost. Therefore, cryoablation should be reserved for the treatment of complex
      tumors. In this article, we will review the different steps of percutaneous renal
      tumor ablation procedures including patient selection, technical considerations,
      and follow-up imaging.

PMID- 21944237
TI  - [New techniques of tumor ablation (microwaves, electroporation)].
AB  - Since the introduction of radiofrequency tumor ablation of liver tumors in the
      late 1990s, local destructive therapies have been applied to lung, renal and bone
      lesions. In addition, new techniques have been introduced to compensate for the
      limitations of radiofrequency ablation, namely the reduced rate of complete
      ablation for tumors larger than 3 cm and tumors near vessels larger than 3 mm.
      Microwave ablation is currently evolving rapidly. While it is a technique based
      on thermal ablation similar to radiofrequency ablation, there are significant
      differences between both techniques. Electroporation, of interest because of the
      non-thermal nature of the ablation process, also is under evaluation.

PMID- 21944238
TI  - [Management of painful bone metastases].
AB  - Bone metastases are frequently symptomatic. The pain is specific due to its
      pathophysiology, characteristics and treatment. Conventional antalgic pain
      management may be insufficient and management should be multifacetted, global and
      multidisciplinary. Interventional radiology procedures widen the range of
      possible antalgic therapies. Their role in the management of patients should be
      defined by a multidisciplinary team on a case-by-case review, based on the
      patient's symptoms and fracture risk. Additional scientific validation of the
      effectiveness of such therapies is needed. Recommendations on the role of
      interventional radiology procedures in the management of patients with
      symptomatic bone metastases are needed to standardize the different practices and
      increase the role of interventional radiology in the management of symptomatic
      bone metastases at the national level. Implementation of the cancer 2009-2012
      project could facilitate the availability of these therapies to patients with
      cancer pain.

PMID- 21944239
TI  - [Pain management in oncology].
AB  - Several interventional radiology procedures are available for the management of
      cancer pain. In this article, we will briefly review the different procedures and
      their value in the setting of cancer pain management under two main categories:
      indirect action (regional anesthesia from neurolysis) and direct action on the
      tumor. Percutaneous ablation of bone tumors: alcohol, laser, radiofrequency,
      microwaves, ultrasound, and cryoablation. Several indications have previously
      been validated, including thermal ablation of bone metastases with results
      superior to conventional therapies. Additional applications should be validated
      over the next few years.

PMID- 21944240
TI  - [Chemoembolization of symptomatic bone metastases: technical considerations and
      therapeutic effectiveness].
AB  - Chemoembolization of bone metastases is defined by the intraarterial perfusion of
      a chemotherapy agent followed by microparticles embolization to improve tissue
      impregnation. This technique increases the local concentration of the
      chemotherapy agent. Tumor response (stable or reduced tumor size) is achieved in
      30-80% of cases with symptomatic relief in over 80% of cases. The indications,
      technical considerations, and effectiveness of this procedure will be reviewed.

PMID- 21944241
TI  - [Rationale for the local treatment of metastases].
AB  - The local treatment of metastases is based on the natural history of the cancer
      and its modifications following medical treatment. Local treatment of metastases
      may be a component of the global treatment of the disease. Local treatment of
      metastases often is entertained for symptomatic relief. There is a theoretical
      analogy between surgery, the gold standard of local treatment, and more recent
      interventional radiology procedures. Local treatment may sometimes lead to
      discontinuation of medical therapy, either permanently or temporarily, and may at
      times provide prolonged complete response. The purpose of this article is to
      further the understanding of the place of local treatment in patients with
      metastatic solid tumors.

PMID- 21944242
TI  - [Radiofrequency ablation of liver and lung tumors].
AB  - Radiofrequency ablation is an image-guided technique of percutaneous tumor
      destruction using high frequency alternating current. Accuracy in needle
      placement and the selection of the imaging modality are key elements of the
      success of the procedure. The volume of ablation with a single needle insertion
      is limited to about 40 mm and the technique is most successful for tumors less
      than 3 cm in diameter with rapid decrease in efficacy for larger tumors. Tumors
      further away from large vessels are also more efficiently treated with this
      technique since heat loss from flowing blood in nearby vessels larger than 3mm
      causes a four-fold increase in treatment failure. Under the best of circumstances
      (tumor less than 25 mm, away from vessels), RF ablation and surgical tumorectomy
      have respective failure rates of 6% and 7,3%. RF ablation of an isolated liver
      metastasis less than 4 cm in diameter results in survival rates at 1, 3 and 5
      years of 97%, 84% and 40% respectively. In the liver, follow-up imaging is
      performed to detect residual tumor characterized by early enhancement. Thin
      peripheral enhancement (less than 1mm) of the necrotic area and well-defined
      triangular shaped regions of enhancement are not signs of tumor recurrence but
      indicate the presence of inflammation or arterial to portal venous fistula. In
      the lung, an area of ground glass attenuation four times larger than the initial
      tumor is a predictive factor of success. PET-CT is the best imaging modality for
      follow-up of lung lesions following RF ablation.

PMID- 21944244
TI  - [CT-guided percutaneous biopsies].
AB  - The number of biopsy requests continuously increases over the years. Similarly,
      lesions that are not amenable to CT-guided biopsy are exceptional due to improved
      imaging guidance and technical advances. The needle tract should preferably go
      through fat, which is less painful and safer. The biopsy should be painless with
      the use of local anesthetics complemented by intravenous sedation. Blunt
      introducers and hydrodissection techniques create access to lesions without
      injury to vessels, bowel loops and fascias. The biopsy samples should be
      processed in accordance with the suspected diagnosis.

PMID- 21944243
TI  - [Intra-arterial treatment of liver metastases from colorectal carcinoma].
AB  - Colorectal carcinoma is a major public health concern with its yearly mondial
      incidence of about one million cases and yearly mortality of 500,000 cases. The
      liver is the organ most frequently affected by metastases with a frequency of 40
      to 60% (contemporaneous in 25% of cases). While surgical resection is the only
      curative therapy, many patients are not such candidates due to the infiltrative
      nature of the liver metastases. Systemic chemotherapy and biotherapy regimens are
      the conventional treatment options for patients with multiple liver metastases.
      Under such circumstances, intra-arterial therapy may play a major role. We will
      review the main types of endovascular therapies for liver metastases from
      colorectal carcinoma including indications, results and potential complications.

PMID- 21944245
TI  - [Ultrasound-guided percutaneous biopsies in 2010].
AB  - Ultrasound-guidance is frequently used at the time of biopsy. Its numerous
      advantages include: lack of ionizing radiation, real-time visualization of the
      needle tip, flexibility to approach lesions from variable and complex angles,
      wide availability of ultrasound units. A certain level of experience is
      nonetheless required to ensure adequate and successful lesion targeting. New
      software are available to assist the operators. "Electromagnetic navigation" can
      assist in locating the needle tip and predicting its trajectory. Image fusion
      with previous cross-sectional imaging studies can assist in detecting lesions
      that are less conspicuous on routine ultrasound images.

PMID- 21944246
TI  - [Fluoroscopy-guided percutaneous biopsies: value of real-time guidance with image
      fusion software].
AB  - Based on our preliminary experience with fluoroscopy-guided biopsy using a real
      time 3D image fusion software, several biopsies may be performed in the
      interventional radiology suite as opposed to under CT guidance: percutaneous lung
      and bone biopsies are easily performed for lesions larger than 15 mm.

PMID- 21944247
TI  - Direct effect of protein kinase C inhibitors on cardiovascular ion channels.
AB  - Protein kinase C (PKC) is a central enzyme that modulates numerous biological
      functions. For this reason, specific PKC inhibitors/ activators are required to
      study PKC-related signaling mechanisms. To date, although many PKC inhibitors
      have been developed, they are limited by poor selectivity and nonspecificity. In
      this review, we focus on the nonspecific actions of PKC inhibitors on
      cardiovascular ion channels in addition to their PKC-inhibiting functions. The
      aim of this paper is to urge caution when using PKC inhibitors to block PKC
      function. This information may help to better understand PKC-related
      physiological/biochemical studies.

PMID- 21944248
TI  - Altered PLCbeta-1 expression in the gerbil hippocampal complex following
      spontaneous seizure.
AB  - Although the phospholipase C (PLC)beta-1 isoform is associated with spontaneous
      seizure and distinctively expressed in the telencephalon, the distribution of
      PLCbeta-1 expression in the epileptic gerbil hippocampus remains controversial.
      Therefore, we determined whether PLCbeta-1 is associated with spontaneous seizure
      in an animal model of genetic epilepsy. In the present study, PLCbeta-1
      immunoreactivity was down-regulated in seizure-sensitive (SS) gerbils more than
      in seizure-resistant (SR) gerbils. The expression of PLCbeta-1 within calretinin
      (CR)- positive neurons was rarely detected within the dentate hilar region of SS
      gerbils. PLCbeta-1 immunoreactivity in the hippocampus was significantly elevated
      as compared to that in pre-seizure SS gerbil 3 h post-ictal. These findings
      suggest that alterations in PLCbeta-1 immunoreactivity in the SS gerbil
      hippocampus may be closely related to the epileptic state of the gerbil brain and
      transiently elevated PLCbeta-1 protein levels following seizure episodes. Such
      alterations may be compensatory responses in the SS gerbil hippocampus.

PMID- 21944249
TI  - The C-terminal domain of PLD2 participates in degradation of protein kinase CKII
      beta subunit in human colorectal carcinoma cells.
AB  - Elevated phospholipase D (PLD) expression prevents cell cycle arrest and
      apoptosis. However, the roles of PLD isoforms in cell proliferation and apoptosis
      are incompletely understood. Here, we investigated the physiological significance
      of the interaction between PLD2 and protein kinase CKII (CKII) in HCT116 human
      colorectal carcinoma cells. PLD2 interacted with the CKIIbeta subunit in HCT116
      cells. The C-terminal domain (residues 578-933) of PLD2 and the N-terminal domain
      of CKIIbeta were necessary for interaction between the two proteins. PLD2
      relocalized CKIIbeta to the plasma membrane area. Overexpression of PLD2 reduced
      CKIIbeta protein level, whereas knockdown of PLD2 led to an increase in CKIIbeta
      expression. PLD2-induced CKIIbeta reduction was mediated by ubiquitin-dependent
      degradation. The C-terminal domain of PLD2 was sufficient for CKIIbeta
      degradation as the catalytic activity of PLD2 was not required. Taken together,
      the results indicate that the C-terminal domain of PLD2 can regulate CKII by
      accelerating CKIIbeta degradation in HCT116 cells.

PMID- 21944250
TI  - A replication study of genome-wide CNV association for hepatic biomarkers
      identifies nine genes associated with liver function.
AB  - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are
      biochemical markers used to test for liver diseases. Copy number variation (CNV)
      plays an important role in determining complex traits and is an emerging area in
      the study various diseases. We performed a genome-wide association study with
      liver function biomarkers AST and ALT in 407 unrelated Koreans. We assayed the
      genome-wide variations on an Affymetrix Genome-Wide 6.0 array, and CNVs were
      analyzed using HelixTree. Using single linear regression, 32 and 42 CNVs showed
      significance for AST and ALT, respectively (P value < 0.05). We compared CNV
      based genes between the current study (KARE2; AST-140, ALT-172) and KARE1 (AST
      1885, ALT-773) using NetBox. Results showed 9 genes (CIDEB, DFFA, PSMA3, PSMC5,
      PSMC6, PSMD12, PSMF1, SDC4, and SIAH1) were overlapped for AST, but no overlapped
      genes were found for ALT. Functional gene annotation analysis shown the
      proteasome pathway, Wnt signaling pathway, programmed cell death, and protein
      binding.

PMID- 21944251
TI  - Phosphorylation of SAV1 by mammalian ste20-like kinase promotes cell death.
AB  - The mammalian ste20-like kinase (MST) pathway is important in the regulation of
      apoptosis and cell cycle and emerges as a novel tumor suppressor pathway. MST
      induced phosphorylation of Salvador homolog 1 (SAV1), which is a scaffold
      protein, has not been evaluated in detail. We performed a mass spectrometric
      analysis of the SAV1 protein that was co-expressed with MST2. Phosphorylation was
      detected at Thr-26, Ser-27, Ser-36 and Ser-269. Although single or double
      mutations had little effects, the mutation of all four residues in SAV1 to Ala
      (SAV1-4A) had inhibitory effects on the MST pathway. MST2-mediated induction of
      SAV1-4A protein levels, SAV1-4A interaction with MST2 and the self-dimerization
      of SAV1-4A were weaker compared to those of wild-type SAV1. SAV1-4A inhibited
      MST2- and K-RasG12V-induced cell death of MCF7 cells. These results suggest that
      MST-mediated phosphorylation of four residues within SAV1 may be important in the
      induction of cell death by the MST pathway.

PMID- 21944252
TI  - Production of methionine gamma- lyase in recombinant Citrobacter freundii bearing
      the hemoglobin gene.
AB  - The production of antileukemic enzyme methionine gamma-lyase (MGL) in distinctly
      related bacteria, Citrobacter freundii and in their recombinants expressing the
      Vitresocilla hemoglobin (VHb) has been studied. This study concerns the potential
      of Citrobacter freundii expressing the Vitreoscilla hemoglobin gene (vgb) for the
      methionine gamma- liyase production. Methionine gamma- liyase production by
      Citrobacter freundii and its vgb(-) and vgb(+) bearing recombinant strain was
      studied in shake-flasks under 200 rpm agitation, culture medium and 30  degrees C
      in a time-course manner. The vgb(+) and especially the carbon type had a dramatic
      effect on methionine gamma- liyase production. The vgb(+) strain of C. freundii
      had about 2-fold and 3.1-fold higher levels of MGL than the host and vgb(-)
      strain, respectively.

PMID- 21944253
TI  - Possible role of Pax-6 in promoting breast cancer cell proliferation and
      tumorigenesis.
AB  - Pax 6, a member of the paired box (Pax) family, has been implicated in
      oncogenesis. However, its therapeutic potential has been never examined in breast
      cancer. To explore the role of Pax6 in breast cancer development, a lentivirus
      based short hairpin RNA (shRNA) delivery system was used to knockdown Pax6
      expression in estrogen receptor (ER)-positive (MCF-7) and ER-negative (MDA-MB
      231) breast cancer cells. Effect of Pax6 silencing on breast cancer cell
      proliferation and tumorigenesis was analyzed. Pax6-RNAi-lentivirus infection
      remarkably downregulated the expression levels of Pax6 mRNA and protein in MCF-7
      and MDA-MB-231 cells. Accordingly, the cell viability, DNA synthesis, and colony
      formation were strongly suppressed, and the tumorigenesis in xenograft nude mice
      was significantly inhibited. Moreover, tumor cells were arrested at G0/G1 phase
      after Pax6 was knocked down. Pax6 facilitates important regulatory roles in
      breast cancer cell proliferation and tumor progression, and could serve as a
      diagnostic marker for clinical investigation.

PMID- 21944254
TI  - HMGB1 regulates autophagy through increasing transcriptional activities of JNK
      and ERK in human myeloid leukemia cells.
AB  - HMGB1 is associated with human cancers and is an activator of autophagy which
      mediates chemotherapy resistance. We here show that the mRNA levels of HMGB1 are
      high in leukemia cells and it is involved in the progression of childhood chronic
      myeloid leukemia (CML). HMGB1 decreases the sensitivity of human myeloid leukemia
      cells K562 to anti-cancer drug induced death through up-regulating the autophagy
      pathway, which is confirmed by the observation with an increase in fusion of
      autophagosomes and autophagolysosomes. When overexpressing HMGB1, both mRNA
      levels of Beclin-1, VSP34 and UVRAG which are key genes involved in mammalian
      autophagy and protein levels of p-Bcl-2 and LC3-II are increased. Luciferase
      assays document that over-expression of HMGB1 increases the transcriptional
      activity of JNK and ERK, which may be silenced by siRNA. The results suggest that
      HMGB1 regulates JNK and ERK required for autophagy, which provides a potential
      drug target for therapeutic interventions in childhood CML.

PMID- 21944255
TI  - Activation of Toll-like receptor 9 and production of epitope specific antibody by
      liposome-encapsulated CpG-DNA.
AB  - Several investigators have shown that CpG-DNA has outstanding effects as a Th1
      responsive adjuvant and that its potent adjuvant effects are enhanced by
      encapsulation with a liposome of proper composition. In this study, we showed
      that encapsulation with phosphatidyl-Beta-oleoyl-gamma-palmitoyl ethanolamine
      (DOPE): cholesterol hemisuccinate (CHEMS) complex enhances the immunostimulatory
      activity of CpG DNA and the binding of CpG-DNA to TLR9. We also examined
      involvement of myeloid differentiation protein (MyD88) and NF-kappaB activation
      in liposome-encapsulated CpG-DNA-induced IL-8 promoter activation. In this
      manuscript, the natural phosphodiester bond CpG-DNA encapsulated by DOPE : CHEMS
      complex is designated as Lipoplex(O). Importantly, we successfully screened B
      cell epitopes of envelope protein (E protein) of hepatitis C virus (HCV-E) and
      attachment glycoprotein G of human respiratory syncytial virus (HRSV-G) by
      immunization with complexes of several peptides and Lipoplex(O) without carriers.
      Therefore, Lipoplex(O) is potentially applicable as a universal adjuvant for
      peptide-based epitope screening and antibody production.

PMID- 21944256
TI  - Reoperative techniques for complications after arterial switch.
AB  - BACKGROUND: The purpose of this study is to review our experience with late
      reoperations after the arterial switch operation (ASO) and to introduce
      reparative solutions adapted from previous techniques. METHODS: A retrospective
      study was performed on 23 patients who underwent late reoperations after ASO
      between 1983 and 2010. Eighteen patients were from our concomitantly reported
      cohort of 258 ASO patients and 5 came from distant referrals. RESULTS: Twenty
      seven reoperations on 23 patients were performed for lesions relating to coronary
      arteries (9 procedures, 7 patients), the neoaortic root (12 procedures, 10
      patients), and the right ventricular outflow tract (6 procedures, 6 patients).
      Four patients died: 1 from an exsanguinating gastric ulcer 4 years after
      prosthetic valve replacement; 1 from coronary occlusion one month postoperatively
      from an unroofed intramural left main coronary artery; and 2 after supravalvar
      pulmonary artery stenosis repair complicated by coexisting left ventricular
      dysfunction from the original ASO. CONCLUSIONS: The ASO remains the treatment of
      choice for transposition of the great arteries and its variants. While the
      incidence of late reintervention is low, a subset of patients will require
      operations that extend the principles of myocardial revascularization, left
      ventricular outflow tract reconstruction, and relief of pulmonary stenosis.

PMID- 21944257
TI  - Outcomes of patients with isolated adrenal metastasis from non-small cell lung
      carcinoma.
AB  - BACKGROUND: Long-term survival of patients who undergo surgical resection of
      isolated adrenal metastasis from non-small cell lung cancer (NSCLC) has been
      reported. The aim of this study was to compare survival of patients who underwent
      adrenalectomy with those treated nonoperatively, and to analyze clinical
      characteristics associated with long-term survival. METHODS: Between January 1994
      and July 2010, 37 patients with isolated adrenal metastasis from NSCLC were
      identified. Twenty patients underwent adrenalectomy. Patients did not undergo
      adrenalectomy owing to suspicion of N2 disease, medical comorbidities, or patient
      preference. Seven patients (35%) treated surgically had tumors that were
      ipsilateral to their primary tumor, and 8 (40%) had metachronous metastases.
      RESULTS: Five-year overall survival was 34% for patients treated operatively and
      0% for patients treated nonoperatively p = 0.002). Among patients treated with
      adrenalectomy, patients with ipsilateral metastases had a 5-year survival of 83%
      compared with 0% for patients with contralateral metastases (p = 0.003). Patients
      without mediastinal nodal disease had a 5-year survival of 52% compared with 0%
      for patients with mediastinal nodal disease (p = 0.008). Survival of patients who
      underwent adrenalectomy for synchronous and metachronous adrenal metastases was
      not significantly different (p = 0.81). CONCLUSIONS: Surgical resection of
      isolated adrenal metastasis from lung cancer provides a survival benefit in well
      selected patients compared with nonoperative management. No patient with
      contralateral adrenal metastases or mediastinal nodal disease survived long term
      after adrenalectomy. The time interval between treatment of the primary lung
      cancer and adrenal metastasis was not significantly associated with survival, but
      the cohort size was small.

PMID- 21944258
TI  - Allograft rejection in patients supported with continuous-flow left ventricular
      assist devices.
AB  - BACKGROUND: Both pulsatile-flow and continuous-flow left ventricular assist
      devices (LVADs) successfully provide patients a bridge to transplantation. Some
      data suggest that continuous-flow pumps increase the risk of allograft rejection,
      contributing to posttransplantation morbidity and mortality. We sought to analyze
      the relationship between LVAD flow characteristics and subsequent allograft
      rejection in bridge to transplant (BTT) patients. METHODS: Patients with LVADs
      from the UTAH Transplant Affiliated Hospitals were retrospectively analyzed.
      Rejection was determined pathologically according to the International Society
      for Heart and Lung Transplantation revised cardiac allograft rejection scale.
      Multimodal statistical analyses were applied. RESULTS: Of 1,076 patients who
      underwent transplantation over a 26-year period, 151 had LVADs. Of these, 111 (77
      pulsatile flow, 34 continuous flow) patients had pathologic data available. There
      was no difference in overall rejection (grades 1R to 3R) between the pulsatile
      flow LVAD and continuous-flow LVAD groups (2.00 +/- 1.43 versus 1.50 +/- 1.16
      episodes/year; p = 0.076.) Patients with pulsatile-flow LVADs had more clinically
      relevant (grades 2R to 3R) rejection than did patients with continuous-flow LVADs
      (0.49 +/- 0.72 versus 0.12 +/- 0.33 episodes/year; p < 0.001). There was no
      survival difference at 1 year (p = 0.920) or 4 years (p = 0.721) after
      transplantation. CONCLUSIONS: Patients with continuous-flow LVADs have similar
      overall rejection rates and a reduced rate of clinically relevant rejection
      compared with patients with pulsatile-flow LVADs during the first year after
      transplantation. Although there is theoretical concern that nonphysiologic,
      nonpulsatile flow could alter the neurohormonal profile of patients in heart
      failure, we are encouraged that the type of LVAD circulation does not influence
      posttransplantation allograft survival.

PMID- 21944259
TI  - Nicotinic acid (niacin): new lipid-independent mechanisms of action and
      therapeutic potentials.
AB  - Nicotinic acid (niacin) has been used for decades to prevent and treat
      atherosclerosis. The well-documented antiatherogenic activity is believed to
      result from its antidyslipidemic effects, which are accompanied by unwanted
      effects, especially a flush. There has been renewed interest in nicotinic acid
      owing to the need for improved prevention of atherosclerosis in patients already
      taking statins. In addition, the identification of a nicotinic acid receptor
      expressed in adipocytes and immune cells has helped to elucidate the mechanisms
      underlying the antiatherosclerotic as well as the unwanted effects of this drug.
      Nicotinic acid exerts its antiatherosclerotic effects at least in part
      independently of its antidyslipidemic effects through mechanisms involving its
      receptor on immune cells as well as through direct and indirect effects on the
      vascular endothelium. Here, we review recent data on the pharmacological effects
      of nicotinic acid and discuss how they might be harnessed to treat other
      inflammatory diseases such as multiple sclerosis or psoriasis.

PMID- 21944260
TI  - The gain in brain: novel imaging techniques and multiplexed proteomic imaging of
      brain tissue ultrastructure.
AB  - The rapid accumulation of neuroproteomics data in recent years has prompted the
      emergence of novel antibody-based imaging methods that aim to understand the
      anatomical and functional context of the multitude of identified proteins. The
      pioneering field of ultrastructural multiplexed proteomic imaging now includes a
      number of high resolution methods, such as array tomography, stimulated emission
      depletion microscopy, stochastic optical reconstruction microscopy and automated
      transmission electron microscopy, which allow a detailed molecular
      characterization of individual synapses and subsynaptic structures within brain
      tissues for the first time. While all of these methods still face considerable
      limitations, a combined complementary approach building on the respective
      strengths of each method is possible and will enable fascinating research into
      the proteomic diversity of the nervous system.

PMID- 21944261
TI  - A Mediterranean-style, low-glycemic-load diet decreases atherogenic lipoproteins
      and reduces lipoprotein (a) and oxidized low-density lipoprotein in women with
      metabolic syndrome.
AB  - The objective was to assess the impact of a Mediterranean-style, low-glycemic
      load diet (control group, n = 41) and the same diet plus a medical food (MF)
      containing phytosterols, soy protein, and extracts from hops and Acacia (MF
      group, n = 42) on lipoprotein atherogenicity in women with metabolic syndrome.
      Plasma lipids, apolipoproteins (apos), lipoprotein subfractions and particle
      size, low-density lipoprotein (LDL) oxidation, and lipoprotein (a) were measured
      at baseline, week 8, and week 12 of the intervention. Three-day dietary records
      were collected at the same time points to assess compliance. Compared with
      baseline, women decreased energy intake from carbohydrate (P < .001) and fat (P <
      .001), whereas they increased energy intake from protein (P < .001). A
      significant increase in energy from monounsaturated fatty acids was also observed
      as well as increases in eicosapentaenoic acid and docosahexaenoic acid, whereas
      trans-fatty acid intake was reduced (P < .00001). The atherogenic lipoproteins,
      large very low-density lipoprotein (P < .0001) and small LDL (P < .0001), were
      reduced, whereas the ratio of large high-density lipoprotein to smaller high
      density lipoprotein particles was increased (P < .0001). Apolipoprotein B was
      reduced for all women (P < .0001), with a greater reduction in the MF group (P <
      .025). Oxidized LDL (P < .05) and lipoprotein (a) (P < .001) were reduced in both
      groups at the end of the intervention. Consumption of a Mediterranean-style diet
      reduces the risk for cardiovascular disease by decreasing atherogenic
      lipoproteins, oxidized LDL, and apo B. Inclusion of an MF may have an additional
      effect in reducing apo B.

PMID- 21944262
TI  - Mediterranean wild plants reduce postprandial platelet aggregation in patients
      with metabolic syndrome.
AB  - Postprandial platelet hyperactivity and aggregation play a crucial role in the
      pathogenesis of metabolic syndrome. The purpose of the present study was to
      evaluate the effect of boiled wild plants consumption on the postprandial
      platelet aggregation in metabolic syndrome patients. Patients consumed 5 meals in
      a random order (ie, 4 wild plant meals, namely, Reichardia picroides [RP], Cynara
      cardunculus, Urospermum picroides [UP], and Chrysanthemum coronarium, and a
      control meal, which contained no wild plants). Several biochemical indices as
      well as platelet activating factor (PAF)- and adenosine diphosphate-induced ex
      vivo platelet aggregation were measured postprandially. Moreover, the ability of
      plants extract to inhibit rabbit platelet aggregation was tested in vitro. The
      consumption of RP and UP meals significantly reduced ex vivo adenosine
      diphosphate-induced postprandial platelet aggregation compared with the control
      meal. The consumption of UP meals significantly reduced the ex vivo PAF-induced
      platelet aggregation postprandially. Both UP and RP extracts significantly
      inhibited PAF-induced rabbit platelet aggregation in vitro. Wild plants
      consumption reduced postprandial platelet hyperaggregability of metabolic
      syndrome patients, which may account for their healthy effects.

PMID- 21944265
TI  - Estimation of prehepatic insulin secretion: comparison between standardized C
      peptide and insulin kinetic models.
AB  - Our aim was to compare traditional C-peptide-based method and insulin-based
      method with standardized kinetic parameters in the estimation of prehepatic
      insulin secretion rate (ISR). One-hundred thirty-four subjects with varying
      degrees of glucose tolerance received an insulin-modified intravenous glucose
      tolerance test and a standard oral glucose tolerance test with measurement of
      plasma insulin and C-peptide. From the intravenous glucose tolerance test, we
      determined insulin kinetics parameters and selected standardized kinetic
      parameters based on mean values in a selected subgroup. We computed ISR from
      insulin concentration during the oral glucose tolerance test using these
      parameters and compared ISR with the standard C-peptide deconvolution approach.
      We then performed the same comparison in an independent data set (231 subjects).
      In the first data set, total ISRs from insulin and C-peptide were highly
      correlated (R(2) = 0.75, P < .0001), although on average different (103 +/- 6 vs
      108 +/- 3 nmol, P < .001). Good correlation was also found in the second data set
      (R(2) = 0.54, P < .0001). The insulin method somewhat overestimated total ISR (85
      +/- 5 vs 67 +/- 3 nmol, P = .002), in part because of differences in insulin
      assay. Similar results were obtained for fasting ISR. Despite the modest bias,
      the insulin and C-peptide methods were consistent in predicting differences
      between groups (eg, obese vs nonobese) and relationships with other physiological
      variables (eg, body mass index, insulin resistance). The insulin method estimated
      first-phase ISR peak similarly to the C-peptide method and better than the simple
      use of insulin concentration. The insulin-based ISR method compares favorably
      with the C-peptide approach. The method will be particularly useful in data sets
      lacking C-peptide to assess beta-cell function through models requiring
      prehepatic secretion.

PMID- 21944263
TI  - Obesity and the hypothalamic-pituitary-adrenal axis in adolescent girls.
AB  - Stress and stress-related concomitants, including hypothalamic-pituitary-adrenal
      (HPA) axis activation, are implicated in obesity and its attendant comorbidities.
      Little is known about this relationship in adolescents. To begin to address this
      important knowledge gap, we studied HPA axis activity in 262 healthy adolescent
      girls aged 11, 13, 15, and 17 years. We hypothesized that obesity would be
      correlated with increased HPA axis activity and reactivity. Measures of HPA axis
      activity included 3 blood samples obtained midday (between 1:00 and 2:00 pm) over
      the course of 40 minutes; overnight urine free cortisol; and cortisol levels 0,
      20, and 40 minutes after venipuncture (cortisol reactivity). Measures of
      adiposity included body mass index (BMI), BMI z score (BMI-Z), percentage body
      fat, and fat distribution (central adiposity) assessed by dual-energy x-ray
      absorptiometry. Daytime levels of serum cortisol were inversely associated with
      BMI-Z and central adiposity (P < .05). The urine free cortisol excretion rate was
      positively correlated with BMI, BMI-Z, and central adiposity. There was blunting
      of cortisol response to venipuncture with increasing adiposity. Our results
      suggest that there may be reduced cortisol levels during the day and increased
      levels at night with increasing degree of adiposity. This study provides
      preliminary findings indicating an alteration of the circadian rhythm of cortisol
      with obesity. We conclude that obesity is associated with altered HPA activity in
      adolescent girls. The clinical implications of our findings require further
      investigation.

PMID- 21944266
TI  - Arachidonic acid and docosahexaenoic acid supplemented to an essential fatty acid
      deficient diet alters the response to endotoxin in rats.
AB  - This study examined fatty acid profiles, triene-tetraene ratios (20:3n9/20:4n6),
      and nutritional and inflammatory markers in rats fed an essential fatty acid
      deficient (EFAD) diet provided as 2% hydrogenated coconut oil (HCO) alone for 2
      weeks or with 1.3 mg of arachidonic acid (AA) and 3.3 mg of docosahexaenoic acid
      (DHA) (AA + DHA) added to achieve 2% fat. Healthy controls were fed an AIN 93M
      diet (AIN) with 2% soybean oil. The HCO and AA + DHA diets led to significant
      reductions of linoleic acid, alpha-linolenic acid, and AA (20:4n6) and increases
      in Mead acid (20:3n9) in plasma and liver compared with the AIN diet; but the
      triene-tetraene levels remained well within normal. However, levels of 20:3n9 and
      20:4n6 were lower in liver phospholipids in the AA + DHA than in HCO group,
      suggesting reduced elongation and desaturation in omega-9 and -6 pathways. The AA
      + DHA group also had significantly lower levels of 18:1n9 and 16:1n7 as well as
      18:1n9/18:0 and 16:1n7/16:0 than the HCO group, suggesting inhibition of stearyl
      Co A desaturase-1 activity. In response to lipopolysaccharide, the levels of
      tumor necrosis factor and interleukin-6 were significantly lower with HCO,
      reflecting reduced inflammation. The AA + DHA group had higher levels of IL-6 and
      C-reactive protein than the HCO group but significantly lower than the AIN group.
      However, in response to endotoxin, interleukin-6 was higher with AA + DHA than
      with AIN. Feeding an EFAD diet reduces baseline inflammation and inflammatory
      response to endotoxin long before the development of EFAD, and added AA + DHA
      modifies this response.

PMID- 21944267
TI  - A higher-carbohydrate, lower-fat diet reduces fasting glucose concentration and
      improves beta-cell function in individuals with impaired fasting glucose.
AB  - The objective was to examine the effects of diet macronutrient composition on
      insulin sensitivity, fasting glucose, and beta-cell response to glucose.
      Participants were 42 normal glucose-tolerant (NGT; fasting glucose <100 mg/dL)
      and 27 impaired fasting glucose (IFG), healthy, overweight/obese (body mass
      index, 32.5 +/- 4.2 kg/m(2)) men and women. For 8 weeks, participants were
      provided with eucaloric diets, either higher carbohydrate/lower fat (55%
      carbohydrate, 18% protein, 27% fat) or lower carbohydrate/higher fat (43:18:39).
      Insulin sensitivity and beta-cell response to glucose (basal, dynamic [PhiD], and
      static) were calculated by mathematical modeling using glucose, insulin, and C
      peptide data obtained during a liquid meal tolerance test. After 8 weeks, NGT on
      the higher-carbohydrate/lower-fat diet had higher insulin sensitivity than NGT on
      the lower-carbohydrate/higher fat diet; this pattern was not observed among IFG.
      After 8 weeks, IFG on the higher-carbohydrate/lower-fat diet had lower fasting
      glucose and higher PhiD than IFG on the lower-carbohydrate/higher-fat diet; this
      pattern was not observed among NGT. Within IFG, fasting glucose at baseline and
      the change in fasting glucose over the intervention were inversely associated
      with baseline PhiD (-0.40, P < .05) and the change in PhiD (-0.42, P < .05),
      respectively. Eight weeks of a higher-carbohydrate/lower-fat diet resulted in
      higher insulin sensitivity in healthy, NGT, overweight/obese individuals, and
      lower fasting glucose and greater glucose-stimulated insulin secretion in
      individuals with IFG. If confirmed, these results may have an impact on dietary
      recommendations for overweight individuals with and without IFG.

PMID- 21944268
TI  - Prevalence and predictors of abnormal arterial function in statin-treated type 2
      diabetes mellitus patients.
AB  - Arterial dysfunction (AD) in type 2 diabetes mellitus (T2DM) predicts
      cardiovascular events. The objective was to investigate the prevalence and
      predictors of AD in statin-treated T2DM patients. We measured flow-mediated (FMD)
      and nitrate-mediated (NMD) brachial artery dilatation in 86 statin-treated T2DM
      patients. Patients were classified into 2 groups: normal arterial function (FMD
      >=3.7% with NMD >=11.9%) or AD (FMD <3.7% with or without NMD <11.9%).
      Endothelial dysfunction without smooth muscle cell dysfunction (ED) was defined
      as FMD less than 3.7% with NMD of at least 11.9%, and endothelial dysfunction
      with smooth muscle cell dysfunction (ED/SMD) was defined as FMD less than 3.7%
      with NMD less than 11.9%. Predictors of arterial function were investigated using
      linear and logistic regression methods. The prevalence of AD was 33.7% (23.2%
      with ED and 10.5% with ED/SMD). In multivariate linear regression, history of
      hypertension (P < .01), statin dose (P < .05), and estimated glomerular
      filtration rate (eGFR) (P = .02) were significant predictors of FMD. Sex (P <
      .01) and creatinine (P = .03) or eGFR (P = .02) predicted NMD. In multivariate
      logistic regression, the independent predictors of AD were history of
      hypertension (odds ratio [OR], 8.79; 95% confidence interval, 2.14-36.12; P <
      .01), age (OR, 1.08; 1.01-1.17; P = .03), and statin dose (OR, 0.33; 0.12-0.87; P
      = .02). A history of hypertension (OR, 8.99; 1.87-43.26; P < .01) was the sole
      independent predictor of ED; eGFR (OR, 0.01; 0.00-0.26; P < .01) independently
      predicted ED/SMD. Our data suggest that one third of statin-treated diabetic
      patients have residual AD, mainly due to ED alone. Earlier identification and
      treatment of hypertension and renal impairment may improve AD and further
      decrease cardiovascular risk in such patients.

PMID- 21944269
TI  - Perilipin 1 ablation in mice enhances lipid oxidation during exercise and does
      not impair exercise performance.
AB  - Perilipin 1 is involved in the control of adipose tissue triacylglycerol
      hydrolysis. Its ablation in mice decreases fat mass and induces a partial
      resistance to diet-induced and genetic obesity. However, the consequences of
      perilipin 1 invalidation on energy balance are not fully defined. Moreover, the
      impact of perilipin 1 ablation on exercise performance and on fatty acids
      mobilization and utilization during exercise has not been studied. We compared
      energy balance (food intake, energy expenditure, spontaneous physical activity)
      and response to exercise of Plin1(-/-) and wild-type mice receiving a chow diet.
      The Plin1(-/-) mice had less fat, comparable food intake, comparable or slightly
      decreased energy expenditure, and no change in spontaneous physical activity.
      Mean 24-hour respiratory quotient was slightly lower, suggesting enhanced fatty
      acid oxidation. Exercise performance (both acute and endurance) was not impaired.
      Changes in nonesterified fatty acid levels during exercise were comparable,
      showing that triacylglycerol mobilization was unimpaired. Oxygen consumption
      increased faster (both tests) and to higher values (acute exercise) in Plin1(-/-)
      mice. Respiratory quotient increased during both types of exercise in Plin1(-/-)
      and control mice, but less in Plin1(-/-) mice. These lower respiratory quotient
      values show that Plin1(-/-) mice rely more on fatty acid oxidation during
      exercise. This is probably related to an overexpression in liver and muscle of
      genes for fatty acids oxidation. Perilipin 1 ablation has limited consequences on
      energy balance. It does not impair exercise performance; fatty acids mobilization
      during exercise is not impaired, whereas their oxidation is enhanced.

PMID- 21944270
TI  - Acute changes in blood glucose do not alter blood glutathione synthesis in
      adolescents with poorly controlled type 1 diabetes mellitus.
AB  - Depletion of blood glutathione (GSH), a key antioxidant, is associated with type
      1 diabetes mellitus (T1D) and contributes to the pathophysiology of diabetes
      complications. The aim of the current study was to determine whether acute
      normalization of blood glucose would restore GSH kinetics in adolescents with
      poorly controlled T1D. Ten 16.9 +/- 1.5-year-old (SE) adolescents who had had T1D
      for 8.5 +/- 1.9 years and were free of complications but were in poor control
      (hemoglobin A(1c), 9.2% +/- 0.5%) received two 5-hour intravenous infusions of L
      [3,3-(2)H(2)]cysteine in the postabsorptive state on 2 separate days after blood
      glucose had been maintained overnight at 246 +/- 24 mg/dL (hyperglycemia) or 118
      +/- 23 mg/dL (euglycemia) using intravenous insulin infusion. Blood GSH
      fractional synthesis rates were determined by mass spectrometry from (2)H(2)
      cysteine incorporation into GSH. Neither blood GSH (551 +/- 169 vs 541 +/- 232
      MUmol/L, P = .629) nor GSH fractional synthesis rate (84% +/- 30% vs 82% +/- 33%
      d(-1), P = .965) was altered by the short-term change in glycemic control. This
      finding suggests that, in adolescents with poorly controlled T1D, either (a)
      blood glucose per se does not regulate GSH metabolism or (b) GSH may only respond
      to sustained, more chronic changes in blood glucose level.

PMID- 21944271
TI  - Effects of vitamin K on the morphometric and material properties of bone in the
      tibiae of growing rats.
AB  - Suboptimal vitamin K nutriture is evident during rapid growth. We aimed to
      determine whether vitamin K(2) (menaquinone-4 [MK-4]) supplementation is
      beneficial to bone structure and intrinsic bone tissue properties in growing
      rats. Male Wistar rats (5 weeks old) were assigned to either a control diet (n =
      8) or an MK-4-supplemented diet (22 mg d(-1) kg(-1) body weight, n = 8). After a
      9-week feeding period, we determined the serum concentration ratio of
      undercarboxylated osteocalcin to gamma-carboxylated osteocalcin and the urinary
      deoxypyridinoline level. All rats were then euthanized, and their tibiae were
      analyzed by micro-computed tomography for trabecular architecture and synchrotron
      radiation micro-computed tomography for cortical pore structure and
      mineralization. Fourier transform infrared microspectroscopy and a
      nanoindentation test were performed on the cortical midlayers of the anterior and
      posterior cortices to assess bone tissue properties. Neither body weight nor
      tibia length differed significantly between the 2 groups. Dietary MK-4
      supplementation decreased the ratio of undercarboxylated osteocalcin to gamma
      carboxylated osteocalcin but did not affect deoxypyridinoline, indicating a
      positive effect on bone formation but not bone resorption. Trabecular volume
      fraction and thickness were increased by MK-4 (P < .05). Neither the cortical
      pore structure nor mineralization was affected by MK-4. On the other hand, MK-4
      increased mineral crystallinity, collagen maturity, and hardness in both the
      anterior and posterior cortices (P < .05). These data indicate the potential
      benefit of MK-4 supplementation during growth in terms of enhancing bone quality.

PMID- 21944272
TI  - Intrauterine growth restriction may not suppress bone formation at term, as
      indicated by circulating concentrations of undercarboxylated osteocalcin and
      Dickkopf-1.
AB  - The objective was to investigate circulating concentrations of bone formation
      markers (undercarboxylated osteocalcin [Glu-OC], an established marker of bone
      formation during fetal and early postnatal life], and Dickkopf-1 [DKK-1], a
      natural inhibitor of osteoblastogenesis during fetal development]) in
      intrauterine-growth-restricted (IUGR; associated with impaired fetal skeletal
      development) and appropriate-for-gestational-age (AGA) pregnancies. Circulating
      concentrations of Glu-OC and DKK-1 were determined by enzyme immunoassay in 40
      mothers and their 20 asymmetric IUGR and 20 AGA singleton full-term fetuses and
      neonates on postnatal day 1 (N1) and 4 (N4). Parametric tests were applied in the
      statistical analysis. No significant differences in Glu-OC concentrations were
      observed between IUGR and AGA groups, whereas fetal DKK-1 concentrations were
      lower in the IUGR group (P = .028). In both groups, maternal Glu-OC and DKK-1
      concentrations were lower than fetal, N1, and N4 concentrations (P <= .012 in all
      cases), whereas fetal Glu-OC concentrations were higher than N1 and N4 ones (P <=
      .037 in all cases). In addition, N1 Glu-OC concentrations were higher than N4
      concentrations (P = .047). Finally, maternal Glu-OC and DKK-1 concentrations
      positively correlated with fetal, N1, and N4 ones (r >= 0.404, P <= .01 in all
      cases). Fetal/neonatal bone formation may not be impaired in full-term asymmetric
      IUGR infants, as indicated by the similar Glu-OC concentrations in both groups.
      Fetal DDK-1 concentrations are lower in the IUGR group, representing probably a
      compensatory mechanism, favoring the formation of mineralized bone.
      Fetal/neonatal bone turnover is markedly enhanced compared with maternal one and
      seems to be associated with the latter in both late pregnancy and early
      postpartum.

PMID- 21944273
TI  - Extreme QT interval prolongation caused by mad honey consumption.
AB  - An unusual type of food poisoning, mad honey poisoning, is a well-known
      phenomenon in the Black Sea region of Turkey. Mad honey poisoning can result in
      severe cardiac complications including sinus bradycardia, nodal rhythm, various
      degrees of atrioventricular blocks, and even asystole. However, no cases of long
      QT interval have been reported so far. This paper reports the first case of
      extremely long QT interval to be associated with mad honey consumption.

PMID- 21944274
TI  - Myocardial infarction mortality and the prediction of cardiogenic shock.

PMID- 21944275
TI  - A successful 4S heart transplantation.
AB  - Donor recipient matching is paramount to successful heart transplantation. The
      presence of allosensitization decreases the transplant candidate's donor pool,
      prolongs the time to transplantation, and increases the post-transplant mortality
      and morbidity. Various strategies are applied to reduce antibody loads with mixed
      results being reported. The development of a new listing criterion by the
      Canadian Cardiac Transplant Network (CCTN) for sensitized patients may overcome
      this problem by increasing the odds that a given recipient receives an organ from
      an appropriately matched donor. The success of this case gives hope to patients
      and provides insights into the treatment of sensitized patients.

PMID- 21944276
TI  - A novel approach to cardiovascular health by optimizing risk management (ANCHOR):
      a primary prevention initiative examining the impact of health risk factor
      assessment and management on cardiac wellness.
AB  - Cardiovascular disease (CVD) represents an increasing burden to health care
      systems. Modifiable risk factors figure prominently in the population
      attributable risk for premature coronary artery disease. Primary care is well
      placed to facilitate CVD risk improvement. We plan to evaluate the ability of a
      novel primary care intervention providing systematic risk factor screening, risk
      weighted behavioural counselling and pharmacological intervention to achieve 2
      objectives: (1) optimized management of global CVD risk of patients and (2)
      increased patient adherence to lifestyle and pharmaceutical interventions aimed
      at decreasing global CVD risk. A pre-post longitudinal prospective design with a
      nonrandomized comparison group is being undertaken in 2 geographically diverse
      primary care practices in Nova Scotia with differing reimbursement models.
      Participants will complete a readiness to change and pre-post health risk
      assessment (HRA), that will trigger a 1-year intervention individualized around
      risk and readiness. The primary outcome will be the proportion of participants
      with Framingham moderate and high-risk strata that reduce their absolute risk by
      10% and 25%, respectively. The secondary outcome will be the proportion of
      moderate and high-risk participants who reduce their risk category. The impact of
      the intervention on clinical and behavioural variables will also be examined. Low
      risk participants will be separately analyzed. Data from participants unable to
      change from the high risk category because of diabetes mellitus or established
      atherosclerotic disease will also be analyzed separately, with changes in
      clinical measures from baseline being assessed. A health economic analysis is
      planned.

PMID- 21944277
TI  - High-dose statin pretreatment for the prevention of contrast-induced nephropathy:
      a meta-analysis.
AB  - BACKGROUND: Contrast-induced nephropathy (CIN) is a rare but serious complication
      following contrast-based procedures. Statins have been postulated to prevent CIN
      via various mechanisms. However, the outcomes following statin administration to
      prevent CIN have been inconsistent. METHODS: A meta-analysis of published
      randomized clinical trials was performed to determine if short-term
      administration of high-dose statin is superior to conventional-dose statin or
      placebo among patients undergoing catheterization and interventional procedures
      in preventing CIN. RESULTS: Data were combined across 8 published clinical trials
      in which 1423 patients were identified. Pooled analyses showed that short-term
      high-dose statin treatment can decrease the occurrence of CIN (risk ratio 0.51,
      95% confidence interval [CI], 0.34-0.77; P=0.001) and 48-hour serum creatinine
      level (standardized mean difference [SMD] -0.07 mg/dL; 95% CI, -0.11 to -0.04
      mg/dL; P<0.00001). However, subgroup analysis showed that statin pretreatment
      cannot decrease the occurrence of CIN in patients with preexisting renal
      impairment (RR 0.90; 95% CI, 0.49-1.65; P=0.73). No evidence of publication bias
      was detected. CONCLUSIONS: This meta-analysis supports the effectiveness of short
      term high-dose statin pretreatment for both decreasing the level of serum
      creatinine and reducing the rate of CIN in patients undergoing diagnostic and
      interventional procedures requiring contrast media. However, prospective clinical
      trials will be needed to draw a definitive conclusion in this area.

PMID- 21944278
TI  - Shock index: a simple clinical parameter for quick mortality risk assessment in
      acute myocardial infarction.
AB  - BACKGROUND: Primary percutaneous coronary intervention (PCI) has become the
      preferred reperfusion strategy in patients with ST-segment elevation myocardial
      infarction and cardiogenic shock. Early identification of patients at risk for
      developing cardiogenic shock allows rapid decision making to determine
      reperfusion and transportation to a PCI centre. The aim of this analysis was to
      evaluate shock index (SI) as a marker for patients at risk of cardiogenic shock.
      METHODS: A total of 644 consecutive patients (73% male) with acute myocardial
      infarction with ST elevations were analyzed retrospectively. Primary PCI was
      performed in 92% of patients, and 7% of patients underwent rescue PCI. The SI
      parameter was defined as the ratio of heart rate to systolic blood pressure at
      hospital admission. RESULTS: SI (odds ratio [OR], 81.26; 95% confidence interval
      [CI], 9.76-676.51; P<0.001), age (OR, 1.17; 95% CI, 1.08-1.26; P<0.001), and
      diabetes (OR, 4.94; 95% CI, 1.44-16.97; P<0.011) were independent predictors of
      mortality. In the group of patients with SI>=0.8, 20% died, whereas in the group
      with SI<0.8, 4% of patients died (P<0.01). CONCLUSIONS: The proposed clinical
      parameter SI correlates with patients' prognosis and could therefore be used as a
      simple indicator of mortality risk of acute myocardial infarction. The simplicity
      of this proposed index makes its use accessible in large-scale clinical practices
      for risk stratification during first contact with patients.

PMID- 21944279
TI  - Temporal smad7 transgene induction in mouse epidermis accelerates skin wound
      healing.
AB  - The expression of Smad7, a tumor growth factor-beta (TGFbeta) antagonist, is
      increased during cutaneous wound healing. To assess this significance, we
      temporally induced Smad7 transgene expression in wounded skin in gene-switch
      Smad7 transgenic (Smad7 tg) mice. Smad7 induction in epidermal keratinocytes
      caused an increase in keratinocyte proliferation with reduced Smad2 activation,
      indicating that Smad7 abrogated TGFbeta-mediated growth inhibition. Additionally,
      wounded skin from Smad7 tg mice exhibited accelerated re-epithelialization, with
      increased activation of extracellular signal-regulated kinase (Erk), and an in
      vitro migration assay revealed that Erk activation contributed to Smad7-mediated
      keratinocyte migration. Notably, epidermis-specific Smad7 transgene expression
      also has a profound effect on the wound stroma, resulting in reduced
      inflammation, angiogenesis, and production of type I collagen. Reduced Smad2
      activation was observed in wounded stroma from Smad7 transgenic (Smad7 tg) mice,
      possibly owing to fewer infiltrated TGFbeta-producing leukocytes compared to
      those in wounds from control mice. Because Smad7 is not secreted, these effects
      could reflect functional changes in Smad7 tg keratinocytes. Supporting this
      notion, the activation of NF-kappaB, a nonsecreted protein complex that
      transcriptionally activates inflammatory cytokines, was reduced in wounded
      epidermis from Smad7 tg mice compared to that in wounded wild-type epidermis. In
      sum, epidermal Smad7 overexpression accelerated wound healing through its direct
      effects on keratinocyte proliferation and migration, and through indirect effects
      on wound stroma.

PMID- 21944280
TI  - Spotlight on bond strength testing--unraveling the complexities.
AB  - The variability in methods and outcomes of bond strength testing reports is well
      documented in the dental literature. Many studies lack important information,
      which impairs the ability to reproduce them as well as to compare them to other
      studies in the literature. In order to critically discuss the important issues
      around bond strength testing methods, and to move closer to at least
      standardizing the reporting of such studies, the Academy of Dental Materials held
      a conference in 2009 entitled Adhesion in Dentistry-Analyzing Bond Strength
      Testing Methods, Variables, and Outcomes. Short synopses of the presentations are
      presented in this article. This article also provides a list of the variables
      that should be reported in bond strength studies, regardless of testing methods,
      to be used by authors conducting future studies, as well as journal reviewers and
      editors. The goal is to provide guidance and a rationale for what should be
      included in a study so that reporting might be more standardized and to enhance
      the possibility that more meaningful comparisons and conclusions may be drawn
      across studies. The table lists detailed descriptions covering all aspects of
      testing procedures, including variables related to tooth substrate, restorative
      material, specimen preparation, pre-testing conditions, testing methods, data
      reporting and analysis.

PMID- 21944282
TI  - Power generation using spinel manganese-cobalt oxide as a cathode catalyst for
      microbial fuel cell applications.
AB  - This study focused on the use of spinel manganese-cobalt (Mn-Co) oxide, prepared
      by a solid state reaction, as a cathode catalyst to replace platinum in microbial
      fuel cells (MFCs) applications. Spinel Mn-Co oxides, with an Mn/Co atomic ratios
      of 0.5, 1, and 2, were prepared and examined in an air cathode MFCs which was fed
      with a molasses-laden synthetic wastewater and operated in batch mode. Among the
      three Mn-Co oxide cathodes and after 300 h of operation, the Mn-Co oxide catalyst
      with Mn/Co atomic ratio of 2 (MnCo-2) exhibited the highest power generation 113
      mW/m2 at cell potential of 279 mV, which were lower than those for the Pt
      catalyst (148 mW/m2 and 325 mV, respectively). This study indicated that using
      spinel Mn-Co oxide to replace platinum as a cathodic catalyst enhances power
      generation, increases contaminant removal, and substantially reduces the cost of
      MFCs.

PMID- 21944281
TI  - In vitro validation of a shape-optimized fiber-reinforced dental bridge.
AB  - OBJECTIVE: To improve its mechanical performance, structural optimization had
      been used in a previous study to obtain an alternative design for a 3-unit inlay
      retained fiber-reinforced composite (FRC) dental bridge. In that study, an
      optimized layout of the FRC substructure had been proposed to minimize stresses
      in the veneering composite and interfacial stresses between the composite and
      substructure. The current work aimed to validate in vitro the improved fracture
      resistance of the optimized design. METHODS: All samples for the 3-unit inlay
      retained FRC dental bridge were made with glass-fibers (FibreKor) as the
      substructure, surrounded by a veneering composite (GC Gradia). Two different FRC
      substructure designs were prepared: a conventional (n=20) and an optimized design
      (n=21). The conventional design was a straight beam linking one proximal box to
      the other, while the optimized design was a curved beam following the lower
      outline of the pontic. All samples were loaded to 400N on a universal test
      machine (MTS 810) with a loading speed of 0.2mm/min. During loading, the force
      and displacement were recorded. Meanwhile, a two-channel acoustic emission (AE)
      system was used to monitor the development of cracks during loading. RESULTS: The
      load-displacement curves of the two groups displayed significant differences. For
      the conventional design, there were numerous drops in load corresponding to local
      damage of the sample. For the optimized design, the load curves were much
      smoother. Cracks were clearly visible on the surface of the conventional group
      only, and the directions of those cracks were perpendicular to those of the most
      tensile stresses. Results from the more sensitive AE measurement also showed that
      the optimized design had, on average, fewer cracking events: 38 versus 2969 in
      the conventional design. SIGNIFICANCE: The much lower number of AE events and
      smoother load-displacement curves indicated that the optimized FRC bridge design
      had a higher fracture resistance. It is expected that the optimized design will
      significantly improve the clinical performance of FRC bridges.

PMID- 21944283
TI  - Adsorption of polycyclic aromatic hydrocarbons (PAHs) on Rhizopus oryzae cell
      walls: application of cosolvent models for validating the cell wall-water
      partition coefficient.
AB  - The cell wall-cosolvent partition coefficients (Km) of polycyclic aromatic
      hydrocarbons (PAHs) were determined for Rhizopus oryzae cell walls by controlling
      the volume fraction of methanol (f) ranging from 0.1 to 0.5. Five cosolvent
      models were employed for extrapolating the cell wall-water partition coefficients
      (Kw) in pure water. The extrapolated Kw values of four PAHs on R. oryzae cell
      walls were ranged from 2.9 to 5.1. Comparison of various Kw values of pyrene
      generated from extrapolation and the QSPR model, together with predicted
      different (PD), mean percentage deviations (MPD), and root mean square errors
      (RSE), revealed that the performance of the LL and Bayesian models were the best
      among all five tested cosolvent models. This study suggests that R. oryzae cell
      walls play an important role in the partitioning of PAHs during bioremediation
      because of the high Kw of fungal cell walls.

PMID- 21944284
TI  - Removal and biodegradation of nonylphenol by immobilized Chlorella vulgaris.
AB  - The removal and biodegradation of nonylphenol (NP) by alginate-immobilized cells
      of Chlorella vulgaris were compared with their respective free cultures. The
      effects of four cell densities of 10(4) per algal bead were investigated, as were
      the four algal bead concentrations, with regard to the removal and biodegradation
      of NP. Although immobilization significantly decreased the growth rate and NP's
      biodegradation efficiency of C. vulgaris, NP removal over a short period was
      enhanced. The NP removal mechanism by immobilized cells was similar to that by
      free cells, including adsorption onto alginate matrix and algal cells, absorption
      within cells and cellular biodegradation. The optimal cell density and bead
      concentration for the removal and biodegradation of NP was 50-100*10(4) cells
      algal bead(-1) and 2-4 beads ml(-1) of wastewater, respectively. These results
      demonstrated that immobilized C. vulgaris cells under optimal biomass and
      photoautotrophic conditions are effective in removing NP from contaminated water.

PMID- 21944285
TI  - Pyrolysis of groundnut de-oiled cake and characterization of the liquid product.
AB  - Renewable biomass is considered as an important energy resource all over the
      world and for an agriculture based economy like that of India, the future
      prospects of being able to convert widely available biomass materials into
      various forms of fuel is most attractive. In this study, pyrolysis of groundnut
      de-oiled cake was investigated with an aim of studying the physical and chemical
      characteristics of the bio-fuel produced and to determine its feasibility as a
      commercial fuel. Thermal pyrolysis of groundnut de-oiled cake was done in a semi
      batch reactor at a temperature range of 200-500  degrees C and at a heating rate
      of 20  degrees C/min. The chemical analysis of the bio-fuel showed the presence
      of functional groups such as alkanes, alkenes, alkynes, aldehydes, ketones,
      carboxylic acids, esters, amines, nitriles, nitro compounds and aromatics rings.
      The physical properties of the bio-fuel obtained were close to that of diesel and
      petrol.

PMID- 21944286
TI  - N-Hydroxyindole-based inhibitors of lactate dehydrogenase against cancer cell
      proliferation.
AB  - Current cancer research is being increasingly focused on the study of distinctive
      characters of tumour metabolism, resulting in a switch from oxidative
      phosphorylation to glycolysis (Warburg effect). Isoform 5 of human lactate
      dehydrogenase (hLDH5), which catalyzes the final step in the glycolytic cascade
      (pyruvate to lactate), constitutes a relatively new and untapped anti-cancer
      target. In this study, careful design and synthesis of a selected series of aryl
      substituted N-hydroxyindole-2-carboxylates (NHIs) has led to several hLDH5
      inhibitors, showing "first-in-class" potency and isoform selectivity. Enzyme
      kinetics studies indicated that these inhibitors exhibit a competitive mode of
      inhibition. Some representative examples were tested against two human pancreatic
      carcinoma cell lines, and displayed a good anti-proliferative activity, which was
      even more evident under hypoxic conditions.

PMID- 21944287
TI  - Synthesis and biological evaluation of new 3-(6-hydroxyindol-2-yl)-5-(Phenyl)
      pyridine or pyrazine V-Shaped molecules as kinase inhibitors and cytotoxic
      agents.
AB  - We here report the synthesis and biological evaluation of new 3-[(2-indolyl)]-5
      phenyl-3,5-pyridine, 3-[(2-indolyl)]-5-phenyl-2,4-pyridine and 3-[(2-indolyl)]-5
      phenyl-2,6-pyrazine derivatives designed as potential CDK inhibitors. Indoles and
      phenyls were used to generate several substitutions of the pyridine and pyrazine
      rings. The synthesis included Stille or Suzuki type reactions, which were carried
      out on the 3,5-dibromopyridine, 2,4-dichloropyridine and 2,6-dichloro-1-4
      pyrazine moieties. Cell effects of the V-shaped family were in the micromolar
      range. Kinase assays were conducted and showed that compound 11 inhibited CDK5
      with an inhibitory concentration of 160 nM with a moderate selectivity over GSK3
      compared to the reference C which exhibited a slightly lower activity on CDK5
      (1.5 MUM). Compound 11 was also found to be the most potent compound in the
      series and was identified as a new lead for DYRK1A inhibitor discovery (IC(50) =
      60 nM). Docking studies were carried out in order to investigate the inhibition
      of DYRK1A.

PMID- 21944288
TI  - Variable effects of dipteran parasitoids and management treatment on grasshopper
      fecundity in a tallgrass prairie.
AB  - Grasshoppers host a number of parasitoids, but little is known about their impact
      on grasshopper life history attributes or how those impacts may vary with land
      use. Here, we report on a three-year survey of nine grasshopper species in a
      tallgrass prairie managed with fire and bison grazing treatments. We measured
      parasitoid prevalence and the impact of parasitoid infection on grasshopper
      fecundity to determine if grasshopper-parasitoid interactions varied with
      management treatment. Adult female grasshoppers were collected every three weeks
      from eight watersheds managed with different prescribed burning and grazing
      treatments. Grasshopper fecundity with and without parasitoids was estimated
      through dissections of reproductive tracts. Dipteran parasitoids from two
      families (Nemestrinidae and Tachinidae) were observed infecting grasshoppers. We
      found significant effects of grazing treatment, but not burn interval, on
      grasshopper-parasitoid interactions. Parasitoids were three times more abundant
      in watersheds with bison grazing than in ungrazed watersheds, and the relative
      abundance of nemestrinid and tachinid flies varied with grazing treatment.
      Parasitoid prevalence varied among grasshopper species from <0.01% infected
      (Mermiria bivittata) to 17% infected (Hypochlora alba). Parasitoid infection
      reduced individual grasshopper fecundity, with stronger effects on current
      reproduction than on past reproduction. Furthermore, current fecundity in
      parasitized grasshoppers was lower in grazed watersheds compared to ungrazed
      watersheds. Nemestrinid parasitoids generally had stronger impacts on grasshopper
      fecundity than tachinid parasitoids, the effects of which were more variable.

PMID- 21944290
TI  - Veterans Affairs general surgery service: the last bastion of integrated
      specialty care.
AB  - BACKGROUND: In a time of increasing specialization, academic training
      institutions provide a compartmentalized learning environment that often does not
      reflect the broad clinical experience of general surgery practice. This study
      aimed to evaluate the contribution of the Veterans Affairs (VA) general surgery
      surgical experience to both index Accreditation Council for Graduate Medical
      Education (ACGME) requirements and as a unique integrated model in which
      residents provide concurrent care of multiple specialty patients. METHODS:
      Institutional review board approval was obtained for retrospective analysis of
      electronic medical records involving all surgical cases performed by the general
      surgery service from 2005 to 2009 at the Nashville VA. Over a 5-year span general
      surgery residents spent an average of 5 months on the VA general surgery service,
      which includes a postgraduate year (PGY)-5, PGY-3, and 2 PGY-1 residents.
      Surgeries involved the following specialties: surgical oncology, endocrine,
      colorectal, hepatobiliary, transplant, gastrointestinal laparoscopy, and elective
      and emergency general surgery. The surgeries were categorized according to ACGME
      index requirements. RESULTS: A total of 2,956 surgeries were performed during the
      5-year period from 2005 through 2009. Residents participated in an average of 246
      surgeries during their experience at the VA; approximately 50 cases are completed
      during the chief year. On the VA surgery service alone, 100% of the ACGME
      requirement was met for the following categories: endocrine (8 cases); skin, soft
      tissue, and breast (33 cases); alimentary tract (78 cases); and abdominal (88
      cases). Approximately 50% of the ACGME requirement was met for liver, pancreas,
      and basic laparoscopic categories. CONCLUSIONS: The VA hospital provides an
      authentic, broad-based, general surgery training experience that integrates
      complex surgical patients simultaneously. Opportunities for this level of
      comprehensive care are decreasing or absent in many general surgery training
      programs. The increasing level of responsibility and simultaneous care of
      multiple specialty patients through the VA hospital systems offers a crucial
      experience for those pursuing a career in general surgery.

PMID- 21944289
TI  - Antioxidants modulate the antiproliferative effects of nitric oxide on vascular
      smooth muscle cells and adventitial fibroblasts by regulating oxidative stress.
AB  - BACKGROUND: S-nitrosothiols (SNO) release nitric oxide (NO) through interaction
      with ascorbic acid (AA). However, little is known about their combined effect in
      the vasculature. The aim of this study was to investigate the effect of AA on SNO
      mediated NO release, proliferation, cell cycle progression, cell death, and
      oxidative stress in vascular cells. METHODS: Vascular smooth muscle cells and
      adventitial fibroblasts harvested from the aortae of Sprague-Dawley rats were
      treated with AA, +/- S-nitrosoglutathione (GSNO), or +/- diethylenetriamine
      NONOate (DETA/NO). NO release, proliferation, cell cycle progression, cell death,
      and oxidative stress were determined by the Griess reaction, [(3)H]-thymidine
      incorporation, flow cytometry, trypan blue exclusion, and 5-(and-6)chloromethyl
      2',7'dichlorodihydrofluorescein staining, respectively. RESULTS: AA increased NO
      release from GSNO 3-fold (P < .001). GSNO and DETA/NO significantly decreased
      proliferation, but AA abrogated this effect (P < .05). Mirroring the
      proliferation data, changes in cell cycle progression induced by GSNO and DETA/NO
      were reversed by the addition of AA. GSNO- and DETA/NO-mediated increases in
      oxidative stress were significantly decreased by the addition of AA (P < .001).
      CONCLUSIONS: Despite causing increased NO release from GSNO, AA reduced the
      antiproliferative and cell cycle effects of GSNO and DETA/NO through the
      modulation of oxidative stress.

PMID- 21944291
TI  - Predictors of relaparotomy after nontrauma emergency general surgery with initial
      fascial closure.
AB  - BACKGROUND: Relaparotomy after emergency surgery for nontrauma intraabdominal
      catastrophes (NTIAC) is morbid. Our objective was to identify patients who likely
      will need on-demand relaparotomy after surgery for NTIAC. METHODS: A
      retrospective chart review of patients from 1998 to 2008 identified cases of
      NTIAC surgery with fascial closure. Demographics, comorbidities, intraoperative
      findings, morbidity, and mortality were analyzed. Relaparotomy was defined as any
      return to the operating room with surgical re-entry of the abdominal cavity.
      RESULTS: A total of 129 patients underwent NTIAC surgery with fascial closure.
      Twenty-nine patients (22%) required relaparotomy and 100 patients (78%) did not.
      Multivariate analysis identified the following predictors of relaparotomy:
      peripheral vascular disease (P = .04), alcohol abuse (P = .02), body mass index
      of 29 kg/m(2) or greater (P = .04), the finding of any ischemic bowel (P = .02),
      and operating room latency of 60 hours or longer (P = .01). Patients with 2 or
      more of these predictors had a 55% risk of relaparotomy whereas patients with
      fewer than 2 of these predictors had a 9% risk (P < .001). CONCLUSIONS: Patients
      whose fascia is closed during NTIAC surgery do worse when they require
      relaparotomy. We have identified preoperative and intraoperative predictors that
      may help identify patients at high risk of on-demand relaparotomy.

PMID- 21944292
TI  - The effects of nicotine on vascular smooth muscle cell chemotaxis induced by
      thrombospondin-1 and fibronectin.
AB  - BACKGROUND: Vascular smooth muscle cell (VSMC) migration is an important process
      in many vascular disorders. Nicotine, thrombospondin-1 (TSP-1) and fibronectin
      (Fn) separately induce VSMC migration. The hypothesis of this study was that
      nicotine treatment of vascular cells would augment TSP-1-induced and Fn-induced
      VSMC migration. METHODS: VSMCs or endothelial cells (ECs) were treated with serum
      free medium or nicotine. Migration of VSMCs was assessed using a modified Boyden
      chemotaxis chamber to serum-free medium, TSP-1, Fn, EC basal medium, and
      conditioned EC medium or nicotine-treated conditioned EC medium alone or with
      supplemented TSP-1 or Fn. RESULTS: Nicotine treatment increased VSMC chemotaxis
      to serum-free medium, but TSP-1 or Fn had no further effect on chemotaxis.
      Conditioned EC and nicotine-treated conditioned EC enhanced VSMC chemotaxis,
      which was further augmented by Fn supplementation. CONCLUSIONS: Nicotine
      stimulated EC derived factors induce VSMC migration, which is augmented by the
      addition of Fn.

PMID- 21944293
TI  - Uncovering the truth about covered stents: is there a difference between covered
      versus uncovered stents with transjugular intrahepatic portosystemic shunts?
AB  - INTRODUCTION: Polytetrafluoroethylene (PTFE)-covered transjugular intrahepatic
      portosystemic shunt (TIPS) stents purportedly provide superior patency. This
      study was undertaken to determine whether covered stents provide better long-term
      patency and outcomes after TIPSs. METHODS: Patients with portal hypertension
      undergoing TIPS at a large teaching hospital from 2001 to 2010 were studied.
      Median data are presented. RESULTS: Two hundred forty-six patients underwent
      TIPS; 70 received uncovered stents, and 176 received covered stents. Patients who
      received uncovered stents had more severely impaired liver function (41% were
      Child class C cirrhotics). The follow-up was longer with uncovered stents (48 vs
      24 months, P < .01). Reinterventions for stenosis were undertaken in 33% with
      uncovered stents versus 19% with covered stents (P = .01). Shunt dysfunction
      occurred in 57% with uncovered stents versus 21% covered (P = .05). A
      deterioration of hepatic function occurred in 31% with uncovered stents versus
      30% with covered (P = .32). Survival with uncovered stents was 31 months versus
      33 months with covered stents (P = .55, Kaplan-Meier). CONCLUSIONS: Covered
      stents may improve patency but do not mitigate postshunt hepatic dysfunction and
      do not improve survival.

PMID- 21944294
TI  - The antiproliferative effects of pterostilbene on breast cancer in vitro are via
      inhibition of constitutive and leptin-induced Janus kinase/signal transducer and
      activator of transcription activation.
AB  - BACKGROUND: The hormone leptin is implicated in breast carcinogenesis in obese
      women. One mechanism is through its activation of Janus kinase/signal transducer
      and activator of transcription (JAK/STAT3) and apoptosis dysregulation. We have
      shown that the antioxidant pterostilbene inhibits proliferation and induces
      apoptosis in breast cancer. Therefore, the goal of this study was to evaluate the
      effect of pterostilbene on cell proliferation and JAK/STAT3 signaling in leptin
      stimulated breast cancer. METHODS: Breast cancer cells were treated with leptin
      alone or in combination with pterostilbene. Detection of cell proliferation and
      JAK/STAT3 signaling were performed using enzyme-linked immunosorbent assay
      protocols. Statistical analysis was performed with analysis of variance and Tukey
      post hoc analysis. RESULTS: Pterostilbene suppresses constitutive as well as
      leptin-induced JAK/STAT3 activation. Pterostilbene treatment also inhibited
      leptin-induced cell proliferation. CONCLUSIONS: Pterostilbene has an inhibitory
      effect on leptin-stimulated breast cancer in vitro through reduction of cell
      proliferation and JAK/STAT3 signaling, a critical regulatory component of
      tumorigenesis in obesity-related breast cancer.

PMID- 21944295
TI  - Understanding the link between psychosocial work stressors and work-related
      musculoskeletal complaints.
AB  - It is well established that psychosocial work stressors relate to employees' work
      related musculoskeletal disorder (WRMSD) symptoms. Using a model investigating
      psychological strain as a mediator between work stressors and WRMSD complaints,
      this study demonstrated that high levels role conflict, low job control, and low
      safety-specific leadership are associated with increased employee strain. Strain,
      in turn, was related to higher levels of WRMSD symptoms of the wrist/hand,
      shoulders, and lower back. Partial mediation of some relationships was also
      found, suggesting that additional meditational mechanisms for the relationships
      between stressors and musculoskeletal symptoms are plausible. This work supports
      the notion that psychosocial stressors in the work environment have important
      links to employee health, especially WRMSDs.

PMID- 21944296
TI  - Building excellence in academic PM&R departments.

PMID- 21944297
TI  - Commentary re.: "Hip strength and knee pain in high school runners: a prospective
      study".

PMID- 21944298
TI  - The effect of symptoms of carpal tunnel syndrome on ultrasonographic median nerve
      measures before and after wheelchair propulsion.
AB  - OBJECTIVE: To quantify median nerve characteristics before and after strenuous
      wheelchair propulsion and relate them to symptoms of carpal tunnel syndrome
      (CTS). We hypothesized that persons with and without symptoms of CTS would have
      significantly different nerve characteristics at baseline and after propulsion.
      DESIGN: A repeated-measures design was used to obtain ultrasound images of the
      median nerve at 3 levels of the wrist (radius, pisiform, and hamate) before and
      after wheelchair propulsion. Investigators were blinded to subject history
      related to CTS. SETTING: The 2007 and 2008 National Veterans Wheelchair Games and
      the Human Engineering Research Laboratories. PARTICIPANTS: Fifty-four
      participants between the ages of 18 and 65 years with a nonprogressive disability
      who used a manual wheelchair as their primary means of mobility completed this
      study. METHODS: Participants completed questionnaires regarding demographics and
      the presence and severity of symptoms of CTS. Ultrasound images of the median
      nerve were obtained before and after a 15-minute strenuous wheelchair-propulsion
      task. MAIN OUTCOME MEASUREMENTS: Baseline values and post-propulsion changes were
      determined for median nerve cross-sectional area, flattening ratio, and swelling
      ratio. Differences in median nerve variables between symptomatic and asymptomatic
      groups were assessed. RESULTS: No significant differences between symptom groups
      were identified at baseline; however, persons with symptoms of CTS showed a
      significantly different percent change from baseline compared with the
      asymptomatic participants for cross-sectional area at pisiform (P = .014) and
      flattening ratio at hamate (P = .022), and they showed a strong trend toward a
      difference in swelling ratio (P = .0502). For each of these variables, the change
      in the symptomatic group was in the opposite direction of the change in the
      asymptomatic group. CONCLUSIONS: We found several median nerve responses to
      wheelchair propulsion associated with symptoms of CTS. These responses occurred
      even though no baseline ultrasound difference was found based on symptoms. Future
      research is necessary to determine how propulsion characteristics (ie, force,
      repetition, and posture) affect the median nerve response.

PMID- 21944299
TI  - Aerobic capacity with hybrid FES rowing in spinal cord injury: comparison with
      arms-only exercise and preliminary findings with regular training.
AB  - OBJECTIVE: To determine the magnitude and range of increases in peak aerobic
      capacity with hybrid-functional electrical stimulation (FES) rowing versus arms
      only rowing in persons with spinal cord injury. DESIGN: Comparison of graded
      exercise tests for peak responses during FES rowing and arms-only rowing.
      Preliminary data on adaptations to FES row training were gathered in a subset of
      individuals. SETTING: Outpatient cardiovascular research laboratory.
      PARTICIPANTS: Six male patients with spinal cord injury (T4-T9, American Spinal
      Injury Association class A). METHODS OR INTERVENTION: Arms-only rowing was
      compared with FES rowing, in which the person who is exercising synchronizes the
      voluntarily controlled upper body movement with the FES-controlled leg movement
      via stimulation to the paralyzed leg muscles. A subgroup (n = 3) completed at
      least 6 months of a progressive FES row training exercise program with graded
      exercise tests every 6 months. MAIN OUTCOME MEASUREMENTS: Peak oxygen
      consumption, peak ventilation, peak respiratory exchange ratio, peak heart rate,
      and peak oxygen pulse. RESULTS: Peak oxygen consumption was greater during FES
      rowing than during arms-only rowing (20.0 +/- 1.9 mL/kg/min versus 15.7 +/- 1.5
      mL/kg/min, P = .01). Peak ventilation was similar, whereas peak respiratory
      exchange ratio and peak heart rate tended to be lower (P = .14 and P = .19,
      respectively). As a result, oxygen pulse was greater by 35% during FES rowing.
      Two of the three persons who completed at least 6 months of FES row training
      demonstrated increases in aerobic capacity greater than those previously observed
      in able-bodied individuals. CONCLUSIONS: FES rowing may provide a more robust
      exercise stimulus for persons with spinal cord injury than most options currently
      available because of the greater aerobic demand.

PMID- 21944300
TI  - Combining visual rehabilitative training and noninvasive brain stimulation to
      enhance visual function in patients with hemianopia: a comparative case study.
AB  - OBJECTIVE: To standardize a protocol for promoting visual rehabilitative outcomes
      in post-stroke hemianopia by combining occipital cortical transcranial direct
      current stimulation (tDCS) with Vision Restoration Therapy (VRT). DESIGN: A
      comparative case study assessing feasibility and safety. SETTING: A controlled
      laboratory setting. PATIENTS: Two patients, both with right hemianopia after
      occipital stroke damage. METHODS AND OUTCOME MEASUREMENTS: Both patients
      underwent an identical VRT protocol that lasted 3 months (30 minutes, twice a
      day, 3 days per week). In patient 1, anodal tDCS was delivered to the occipital
      cortex during VRT training, whereas in patient 2 sham tDCS with VRT was
      performed. The primary outcome, visual field border, was defined objectively by
      using high-resolution perimetry. Secondary outcomes included subjective
      characterization of visual deficit and functional surveys that assessed
      performance on activities of daily living. For patient 1, the neural correlates
      of visual recovery were also investigated, by using functional magnetic resonance
      imaging. RESULTS: Delivery of combined tDCS with VRT was feasible and safe. High
      resolution perimetry revealed a greater shift in visual field border for patient
      1 versus patient 2. Patient 1 also showed greater recovery of function in
      activities of daily living. Contrary to the expectation, patient 2 perceived
      greater subjective improvement in visual field despite objective high-resolution
      perimetry results that indicated otherwise. In patient 1, visual function
      recovery was associated with functional magnetic resonance imaging activity in
      surviving peri-lesional and bilateral higher-order visual areas. CONCLUSIONS:
      Results of preliminary case comparisons suggest that occipital cortical tDCS may
      enhance recovery of visual function associated with concurrent VRT through visual
      cortical reorganization. Future studies may benefit from incorporating protocol
      refinements such as those described here, which include global capture of
      function, control for potential confounds, and investigation of underlying neural
      substrates of recovery.

PMID- 21944301
TI  - Caregiver ratings of long-term executive dysfunction and attention problems after
      early childhood traumatic brain injury: family functioning is important.
AB  - OBJECTIVE: To evaluate the relationship of family and parenting factors to long
      term executive dysfunction and attention problems after early childhood traumatic
      brain injury (TBI). We hypothesized that the magnitude of executive dysfunction
      and attention problems would be moderated by family and parenting factors.
      DESIGN: A multicenter, prospective cohort study that included an orthopedic
      injury (OI) reference group. SETTING: Three tertiary academic children's hospital
      medical centers and one general medical center. PARTICIPANTS: Children, ages 3-7
      years, hospitalized for OI, moderate TBI, or severe TBI. METHODS AND OUTCOME
      MEASUREMENTS: Parental ratings of family functioning and parenting styles were
      obtained 18 months after the injury occurred. The main outcome measurements,
      which were parental ratings of children's executive function and attention, were
      performed at least 24 months after the injury occurred (mean, 39 months; range,
      25-63 months). ANALYSIS: Group comparisons were conducted with use of t-tests,
      chi(2) analysis, analysis of variance, and Pearson and Spearman correlations.
      Regression analysis was used to examine associations of the outcomes with family
      functioning and parenting styles and to test moderating effects of these factors
      on group differences. RESULTS: Participants with severe TBI demonstrated
      increased executive dysfunction and attention problems compared with those who
      sustained moderate TBI or OI. Lower levels of family dysfunction were associated
      with better executive function and attention across groups but did not moderate
      group differences. However, attention deficits after severe TBI were exacerbated
      under conditions of more permissive parenting relative to attention deficits
      after OIs. CONCLUSIONS: Executive function and attention problems persisted on a
      long-term basis (>24 months) after early childhood TBI, and positive global
      family functioning and nonpermissive parenting were associated with better
      outcomes. Better characterization of the optimal family environment for recovery
      from early childhood TBI could help target future interventions.

PMID- 21944302
TI  - A systematic literature review of outcome measures for upper extremity function
      using the international classification of functioning, disability, and health as
      reference.
AB  - OBJECTIVE: To provide information regarding the (1) responsiveness and
      reliability of different outcome measures used with persons who have impairments
      in upper extremity function and (2) their content validity based on the
      International Classification of Functioning, Disability, and Health (ICF). DATA
      SOURCES: MEDLINE, CINAHL, PsycINFO, and EMBASE databases were systematically
      searched for studies on outcome measures used to evaluate upper extremity
      function; only studies written in English and published between July 1997 and
      July 2010 were considered. STUDY SELECTION: One investigator reviewed titles and
      abstracts of the identified studies to determine whether the studies met
      predefined eligibility criteria (eg, study design, age <18 years). Another
      investigator did the same for 70% of the studies. DATA EXTRACTION: All types of
      outcome measures in the included studies were extracted, and the information
      retrieved from these outcome measures was linked to the ICF by 2 independent
      investigators who used standardized linking rules. In addition, studies reporting
      the clinical responsiveness, interrater reliability, and test-retest reliability
      of the outcome measures were identified. DATA SYNTHESIS: From among the 894
      studies that were included in this review, 17 most frequently used outcome
      measures in the different study populations were identified. Five were patient
      reported outcome measures and 12 were clinical outcome measures. The outcome
      measures show large variability with regard to the areas of functioning and
      disability addressed. Reliability and responsiveness data are missing for a few
      outcome measures or for certain populations for which they have been used.
      CONCLUSION: This systematic review provides an overview of the outcome measures
      used to address functioning and disability as they are related to the upper
      extremity. The results of this study may help clinicians and researchers select
      the most appropriate outcome measure for their clinical population or research
      question according to ICF-based content validity, and additional information on
      the reliability and responsiveness of the measures is provided. Our findings also
      can provide directions for further research.

PMID- 21944303
TI  - Influence of sports participation on bone health in the young athlete: a review
      of the literature.
AB  - Peak bone mass is attained during the second and third decades of life. Sports
      participation during the years that peak bone mass is being acquired may lead to
      adaptive changes that improve bone architecture through increased density and
      enhanced geometric properties. A review of the literature evaluating sports
      participation in young athletes, ages 10-30 years, revealed that sports that
      involve high-impact loading (eg, gymnastics, hurdling, judo, karate, volleyball,
      and other jumping sports) or odd-impact loading (eg, soccer, basketball, racquet
      games, step-aerobics, and speed skating) are associated with higher bone mineral
      composition, bone mineral density (BMD), and enhanced bone geometry in anatomic
      regions specific to the loading patterns of each sport. Repetitive low-impact
      sports (such as distance running) are associated with favorable changes in bone
      geometry. Nonimpact sports such as swimming, water polo, and cycling are not
      associated with improvements in bone mineral composition or BMD, and swimming may
      negatively influence hip geometry. Participating in sports during early puberty
      may enhance bone mass. Continued participation in sports appears to maintain the
      full benefits of increased peak bone mass, although former athletes who do not
      maintain participation in sports may retain some benefits of increased BMD. Long
      term elite male cycling was reported to negatively influence bone health, and
      female adolescent distance running was associated with suppressed bone mineral
      accrual; confounding factors associated with participation in endurance sports
      may have contributed to those findings. In summary, young men and women who
      participate in sports that involve high-impact or odd-impact loading exhibit the
      greatest associated gains in bone health. Participation in nonimpact sports, such
      as swimming and cycling, is not associated with an improvement in bone health.

PMID- 21944304
TI  - The limitations of statistical adjustment.

PMID- 21944305
TI  - Driving after stroke: what are the appropriate criteria?

PMID- 21944306
TI  - A rare cause of leg pain in a triathlete.

PMID- 21944307
TI  - Structured video gaming as affordable visual restoration therapy.

PMID- 21944308
TI  - Magnetic resonance imaging findings in acquired myopathy.

PMID- 21944309
TI  - Endoscopic papillary large-balloon dilation combined with endoscopic biliary
      sphincterotomy for the removal of bile duct stones (with video).

PMID- 21944310
TI  - Drug-eluting/biodegradable stents.

PMID- 21944311
TI  - Endoscopic band ligation for colonic diverticular hemorrhage.
AB  - BACKGROUND: The number of sample cases of colonic diverticular hemorrhage treated
      with endoscopic band ligation (EBL) has been small to date. OBJECTIVE: To
      elucidate the safety and efficacy of EBL for colonic diverticular hemorrhage.
      DESIGN: Retrospective study. SETTING: General hospital. PATIENTS: A total of 29
      patients with 31 colonic diverticula with stigmata of recent hemorrhage (SRH).
      INTERVENTIONS: Urgent colonoscopy was performed after bowel preparation. When
      diverticula with SRH were identified, marking with hemoclips was done near the
      diverticula. The endoscope was removed and reinserted after a band-ligator device
      was attached to the tip of endoscope. At first, EBL was attempted. In patients
      who could not be treated with EBL, epinephrine injection or endoscopic clipping
      was performed. MAIN OUTCOME MEASUREMENTS: Procedure time, rate of hemostasis and
      rebleeding, complications. RESULTS: The mean procedure time was 47 +/- 19
      minutes. EBL was successfully completed in 27 colonic diverticula (87%); except
      in 3 diverticula with a small orifice and large dome and 1 diverticula in which
      the orifice was too large. Early rebleeding after EBL occurred in 3 of 27 cases
      (11%). Although 2 cases of sigmoid rebleeding could be managed by repeat EBL or
      conservatively, right hemicolectomy was performed in 1 ascending diverticulum, in
      which the bleeding source was not identified on repeat colonoscopy. Scar
      formation at previously banded diverticula was identified in 7 of 11 patients who
      underwent follow-up colonoscopy. There were no complications after EBL in any of
      the patients. LIMITATIONS: Retrospective study. CONCLUSIONS: EBL is a safe and
      effective treatment for colonic diverticular hemorrhage, and colonic diverticula
      resolve after EBL.

PMID- 21944312
TI  - Duodenal carcinoid tumors: 5 cases treated by endoscopic submucosal dissection.

PMID- 21944313
TI  - Endoscopic full-thickness resection in the colon by using a clip-and-cut
      technique: an animal study.
AB  - BACKGROUND: Although endoscopic resection techniques have been established for
      definitive therapy of mucosal neoplasia, complete histopathological assessment or
      resection of subepithelial lesions is not reliably possible. OBJECTIVE: To
      overcome these limitations, a novel endoscopic full-thickness resection (EFTR)
      and closure technique was developed. DESIGN: Animal survival study. ANIMALS:
      Eight female domestic pigs. INTERVENTIONS: Two-centimeter artificial distal
      colonic lesions were created endoscopically. EFTR of the lesions was attempted
      using a prototype device, which consists of a large transparent plastic cap with
      a preloaded snare and a modified over-the-scope clip. After the procedure, half
      of the animals were killed after 7 days, and the other half after 28 days. MAIN
      OUTCOME MEASUREMENTS: Complete resection (all markings included in the specimen),
      technical success, complication rates, and wound healing on follow-up autopsy and
      histology. RESULTS: EFTR of healthy colonic tissue was possible in all cases; 2
      additional clips had to be placed for complete closure in 1 case. In 1 animal,
      the preloaded closure failed, and the animal was prematurely killed. All other
      animals had an uneventful postoperative course. Necropsy and histopathological
      evaluation demonstrated well-healed resection sites with no evidence of intra
      abdominal infection or inadvertent organ inclusion. LIMITATIONS: Animal model,
      resection of healthy tissue. CONCLUSION: This novel device allows for reliable
      full-thickness resection and closure of 2-cm specimens of the colonic wall in a
      single procedure as well as reliable wound healing of EFTR defects.

PMID- 21944315
TI  - Gastric perforation caused by a pancreatic pseudocyst.

PMID- 21944314
TI  - Reflectance confocal microscopy for the diagnosis of eosinophilic esophagitis: a
      pilot study conducted on biopsy specimens.
AB  - BACKGROUND: Diagnosis of eosinophilic esophagitis (EoE) currently requires
      endoscopic biopsy and histopathologic analysis of the biopsy specimens to count
      intraepithelial eosinophils. Reflectance confocal microscopy (RCM) is an
      endomicroscopy technology that is capable of obtaining high-resolution, optically
      sectioned images of esophageal mucosa without the administration of exogenous
      contrast. OBJECTIVE: In this study, we investigated the capability of a high
      speed form of RCM, termed spectrally encoded confocal microscopy (SECM), to count
      intraepithelial esophageal eosinophils and characterize other microscopic
      findings of EoE. DESIGN: A total of 43 biopsy samples from 35 pediatric patients
      and 8 biopsy samples from 8 adult patients undergoing EGD for EoE were imaged by
      SECM immediately after their removal and then processed for routine
      histopathology. Two SECM readers, trained on adult cases, prospectively counted
      intraepithelial eosinophils and detected the presence of abscess, degranulation,
      and basal cell hyperplasia on SECM images from the pediatric patients. A
      pathologist blinded to the SECM data analyzed the same from corresponding slides.
      SETTING: The Gastrointestinal Unit, Massachusetts General Hospital. RESULTS:
      Eosinophils by SECM demonstrated a higher reflectance than the surrounding cells
      and other inflammatory cells. There was good correlation between SECM and
      histology maximum eosinophil counts/high-power field (R = 0.76, P < .0001). Intra
      and interobserver correlations for SECM counts were very good (R = 0.93 and R =
      0.92, respectively; P < .0001). For the commonly used eosinophil count cutoff of
      15 per high-power field, the sensitivity and specificity of SECM for EoE were
      100%. The sensitivity and specificity for abscess, degranulation, and basal cell
      hyperplasia were 100% and 82%, 91% and 60%, and 94% and 80%, respectively. Intra-
      and interobserver agreements for these microscopic features of EoE were very good
      (kappa = 0.9/0.9, 0.84/1.0, 0.91/0.81, respectively). LIMITATION: Ex vivo study.
      CONCLUSIONS: This study demonstrates that RCM can be used to accurately count
      intraepithelial eosinophils and identify other microscopic abnormalities
      associated with EoE on freshly excised biopsy samples. These findings suggest
      that RCM may be developed into a tool for assessing eosinophilic infiltration in
      the esophagus in vivo.

PMID- 21944316
TI  - Two-point fixed endoscopic submucosal dissection in rectal tumor (with video).
AB  - BACKGROUND: Polypectomy, EMR, transanal endoscopic microsurgery, and surgery have
      been performed as treatments of rectal tumors. Endoscopic procedures are the
      least-invasive treatments for patients. Complete resection of the lesion is
      required to prevent its recurrence, and endoscopic submucosal dissection (ESD)
      has begun to be performed. With increasing requirements for safety, reliability,
      and simplicity in ESD, we decided to use a 2-point fixed ESD with a transparent
      hood fitted with a mucosal forceps channel in a case of a rectal tumor and report
      its usefulness. OBJECTIVE: To evaluate the safety, simplicity, and usefulness of
      2-point fixed ESD performed on a rectal tumor. DESIGN: Case series. SETTING:
      Kanagawa Cancer Center Hospital. MAIN OUTCOME MEASUREMENTS: Safety, simplicity,
      and usefulness of 2-point fixed ESD performed on a rectal tumor. RESULTS: The
      mean duration of the procedure was 45 minutes (range 30-110 minutes). Hemostasis
      and manipulation of the vessels were easy in all patients who did not have
      postoperative bleeding, perforation, or retroperitoneal emphysema as
      complications. LIMITATIONS: Uncontrolled study. CONCLUSION: This study of 2-point
      ESD performed in 12 patients with rectal lesions revealed that the 2-point ESD
      with a transparent hood fitted with a mucosal forceps channel is a useful
      auxiliary device, enabling safe and reliable ESD on a rectal lesion.

PMID- 21944318
TI  - Risk signals of an influenza pandemic caused by highly pathogenic avian influenza
      subtype H5N1: spatio-temporal perspectives.
AB  - Highly pathogenic avian influenza (HPAI) subtype H5N1 is a trans-boundary animal
      disease that has crossed the animal-human species barrier and over the past
      decade has had a considerable impact on the poultry industry, wild bird
      populations and on human health. Understanding the spatio-temporal patterns of
      H5N1 outbreaks can provide visual clues to the dynamics of disease spread and of
      areas at risk, and thus improve the cost-effectiveness of disease control and
      prevention. This study describes the characteristics and investigates the
      temporal, spatial and space-time dynamics of H5N1 outbreaks in domestic poultry
      between December 2003 and December 2009 using a global database. The study found
      that the start date of the epidemic wave was postponed, the duration of the
      epidemic was prolonged and its magnitude reduced over time, but the disease
      transmission cycle was not efficiently interrupted. Two 'hot-spot' regions of
      H5N1 outbreaks were identified: well-documented locations in East and Southeast
      Asia, as well as a novel location at the boundaries of Europe and Africa, where
      enhanced surveillance should be conducted. The risk of a pandemic due to H5N1
      remains high.

PMID- 21944319
TI  - Inhibiting matrix metalloproteinase by cell-based timp-3 gene transfer
      effectively treats acute and chronic ischemic cardiomyopathy.
AB  - After a myocardial infarction (MI), an increase in the cardiac ratio of matrix
      metalloproteinases (MMPs) relative to their inhibitors (TIMPs) causes
      extracellular matrix modulation that leads to ventricular dilatation and
      congestive heart failure. Cell therapy can mitigate these effects.  In this
      study, we tested whether increasing MMP inhibition via cell-based gene transfer
      of Timp-3 further preserved ventricular morphometry and cardiac function in a rat
      model of MI. We also measured the effect of treatment timing. We generated MI
      (coronary artery ligation) in adult  rats. Three or 14 days later, we implanted
      medium (control) or vascular smooth muscle cells transfected with empty vector
      (VSMCs) or Timp-3 (C-TIMP-3) into the peri-infarct region (n = 15-24/group). We
      assessed MMP-2 and -9 expression and activity, TIMP-3, and TNF-alpha  expression,
      cell apoptosis, infarct size and thickness, ventricular morphometry, and cardiac
      function (by echocardiography). Relative to medium, VSMCs delivered at either
      time point significantly reduced cardiac expression and activity of MMP-2 and -9,
      reduced expression of TNF-alpha, and  increased expression of TIMP-3. Cell
      therapy also reduced apoptosis and scar area, increased infarct thickness,
      preserved ventricular structure, and reduced functional loss. All these effects
      were augmented by C-TIMP-3 treatment. Survival and cardiac function were
      significantly greater when  VSMCs or C-TIMP-3 were delivered at 3 (vs. 14) days
      after MI. Upregulating post-MI cardiac TIMP-3 expression via cell-based gene
      therapy contributed additional regulation of MMP, TIMP, and TNF-alpha levels,
      thereby boosting the structural and functional effects of VSMCs transplanted at 3
      or 14 days after an MI in rats. Early treatment may be superior to late, though
      both are effective.

PMID- 21944320
TI  - Discovering knowledge of medical quality in total hip arthroplasty (THA).
AB  - As the incidence of THA is expected to rise with an aging population and
      improvements in surgery, a satisfactory outcome in health care can effectively
      increase medical quality. This paper uses a serious data screening function by
      THA physician to reduce data dimension after data collected from the NHI
      database, then 8576 cases are obtained from the original cases of 10,388 after
      screening procedure. The proposed model adopts an imbalanced sampling method to
      solve class imbalance problem, and utilizes rough set to locate core attributes.
      Based on the core attributes, the extracted rules can be comprehensive for the
      rules of medical quality. In verification, THA dataset is taken as case study;
      the performance of the proposed model is verified and compared with other data
      mining methods under some criteria. And the generated decision rules and core
      attributes could find more managerial implication. Moreover, the result can
      provide stakeholders with useful THA information to help to make decision.

PMID- 21944317
TI  - Optical technologies and molecular imaging for cervical neoplasia: a program
      project update.
AB  - There is an urgent global need for effective and affordable approaches to
      cervical cancer screening and diagnosis. In developing nations, cervical
      malignancies remain the leading cause of cancer-related deaths in women. This
      reality may be difficult to accept given that these deaths are largely
      preventable; where cervical screening programs have been implemented, cervical
      cancer-related deaths have decreased dramatically. In developed countries, the
      challenges of cervical disease stem from high costs and overtreatment. The
      National Cancer Institute-funded Program Project is evaluating the applicability
      of optical technologies in cervical cancer. The mandate of the project is to
      create tools for disease detection and diagnosis that are inexpensive, require
      minimal expertise, are more accurate than existing modalities, and can be
      feasibly implemented in a variety of clinical settings. This article presents the
      status and long-term goals of the project.

PMID- 21944322
TI  - [The difficulty in taking geriatrics in pre-graduate medicine].

PMID- 21944321
TI  - Age-specific incidence ratios of lung cancer (LC) in Turkey: LC in older people
      is increasing.
AB  - Life expectancy has greatly increased in the last century. In the last decades,
      cancer in the older people has become an increasingly common problem owing to the
      prolonged life-expectancy of the general population and to the improved
      management of common cancers. The aim of this study was to demonstrate the age
      specific incidence ratios in patients with LC. Data were collected from hospital
      based registries from 1988 to 2007. A total of 10,881 patients were assessed. The
      median age at diagnosis was 60 years. When compared to Surveillance Epidemiology
      and End Results (SEER) data, these values were found to be 10 years younger than
      American patients. Trends consist of the median ages of patients were increased
      during years (p<0.001). Along the years, especially in the last years, the ratios
      of cancer patients of older than 70 years were significantly increased among the
      cancer patient populations. In conclusion, LC in older person has become an
      increasingly common problem in the last years.

PMID- 21944323
TI  - [Functional impairment as an expression of an uncommon disease in the elderly].

PMID- 21944324
TI  - [Is it appropriate to reduce hospital admissions in institutionalised patients?].

PMID- 21944325
TI  - [Capgras syndrome: a proposal of neuropsychological battery for assessment].
AB  - Capgras syndrome is the most prevalent of the delusional misidentification
      syndromes. It appears in both psychiatric illness and organic brain damage.
      Cognitive and neuropsychiatric models (lateralization and disconnection) have
      been proposed to explain the syndrome. From a neuropsychological point of view
      Capgras syndrome seems to be due to damage of bifrontal and right limbic and
      temporal regions. Memory, feeling of familiarity, monitoring of self and reality
      would be altered. All of these cause a failure to adequately integrate the
      information about emotions and facial recognition. Relative preservation of the
      left frontal lobe may be necessary for the development of delusional response.
      There does not seem to be a differential pattern as regards the aetiology, but
      there is a common underlying neuropsychiatric mechanism. Based on theoretic
      models, and clinics features, we propose a neuropsychological battery to assess
      the Capgras syndrome, that should be sensitive to the main expected deficits.

PMID- 21944326
TI  - [Frailty screening in primary care].

PMID- 21944327
TI  - [Magnitude of the problem of falls in a regional network of Spanish nursing
      homes].

PMID- 21944328
TI  - [Evaluation of an intervention program in nursing homes to reduce hospital
      attendance].
AB  - OBJECTIVES: This study describes the outcomes of an intervention program in
      Nursing Homes and their effects on emergency room attendance, hospital
      admissions, and pharmaceutical expenditure. MATERIAL AND METHODS: This involved
      non-randomised community intervention in Nursing Homes with a control group. The
      program was implemented gradually from 2007 to 2009 in 10 Nursing Homes (857
      beds) which participated voluntarily. The control group consisted of 14 Nursing
      homes (1,200 beds), which refused to participate or were not assigned to our
      Primary Care centres. Intervention consisted of comprehensive geriatric
      assessment and follow-up visits by trained personnel, review and adjustment of
      drug treatment, case management and staff training. RESULTS: In the Nursing Homes
      where the program was carried out, emergency room attendance decreased from
      11650/00 (95%CI 1100-1240]) in 2006 to 6740/00 (95%CI 620-730) in 2009, while in
      the control group it increased from 1071 (95%CI 1020-1130) to 12460/00 (95%CI
      1190-1310). The hospital admissions also decreased from 48.4% (95%CI 45-52) in
      2006 to 32.1% (95%CI 29-35) in 2009, while in the control group increased from
      43.5% (95%CI 41-46) to 55.8% (95%CI 53-59). There was also a 9% reduction in
      pharmacy cost compared with an increase of 11.9% in the control group.
      CONCLUSIONS: The intervention has proved effective at reducing hospital
      admissions and emergency room attendance in institutionalised patients, thereby
      streamlining pharmacy costs.

PMID- 21944329
TI  - A what? Subcapsular biloma after laparoscopic cholecystectomy.

PMID- 21944330
TI  - Salmonella typhi breast abscess: an uncommon manifestation of an uncommon disease
      in the United States.

PMID- 21944331
TI  - Type a aortic dissection in association with alpha-1-antitrypsin deficiency.

PMID- 21944332
TI  - Duodenal diverticulum: an unusual cause of high-grade duodenal obstruction.

PMID- 21944333
TI  - Bilateral synchronous breast cancer in a male.

PMID- 21944334
TI  - Surgical resection of small bowel plasmablastic lymphoma for chronic bleeding.

PMID- 21944335
TI  - Pyoderma gangrenosum of the breast after bilateral simple mastectomies for ductal
      carcinoma in situ.

PMID- 21944336
TI  - Laparoscopic resection of lesser curve gastrointestinal stromal tumor.

PMID- 21944337
TI  - Parastomal small bowel evisceration as a result of parastomal pyoderma
      gangrenosum in a patient with Crohn's disease.

PMID- 21944338
TI  - Appendicitis differences in severity and treatment in a border community
      hospital.

PMID- 21944339
TI  - Managing influence and conflict of interest with professionalism.

PMID- 21944340
TI  - Application of a tertiary referral scoring system to predict nonreversal of
      Hartmann's procedure for diverticulitis in a community hospital.
AB  - Riansuwan et al. at Cleveland Clinic developed a scoring system to quantify the
      risk of Hartmann's nonreversal based on age, preoperative transfusion, pulmonary
      comorbidity, American Society of Anesthesiologists score, perforation, and
      anticoagulation. Our study validates the scoring  system in a community hospital
      setting. Patients undergoing Hartmann's procedure for diverticulitis (2006 to
      June 2009) were identified from our hospital's database. Two groups were formed
      based on Hartmann's reversal within 1 year and those with nonreversal. An
      independent-sample t  test and logistic regression using score and nine other
      variables as predictors of Hartmann's nonreversal were run. Sixty-three of 93
      patients (67.7%) had a Hartmann's reversal. Higher scores and higher mean age
      were seen in the nonreversal group (15.5 +/- 3.0 vs 12.1 +/-  2.5 and 73 +/- 15
      vs 63 +/- 14 years, respectively). Patients with scores 18 or above were not
      reversed; 43 of 49 patients (88%) with scores of 13 or less were reversed.
      Logistic regression confirmed that the only predictive variable for nonreversal
      is a higher score. The  scoring system is predictive of nonreversibility of
      Hartmann's procedure for acute diverticulitis. This will be useful in allowing
      surgeons to strategize accurately and to counsel patients realistically. Higher
      scores may allow both the surgeon and patient to have a low threshold for
      exploring  alternatives to Hartmann's procedure.

PMID- 21944341
TI  - General surgery at rural Tennessee hospitals: a survey of rural Tennessee
      hospital administrators.
AB  - Rural communities face an impending surgical workforce crisis. The purpose of
      this study is to describe perceptions of rural Tennessee hospital administrators
      regarding the importance of surgical services to their hospitals. In
      collaboration with the Tennessee Hospital Association,  we developed and
      administered a 13-item survey based on a recently published national survey to 80
      rural Tennessee hospitals in August 2008. A total of 29 responses were received
      for an overall 36.3 per cent response rate. Over 44 per cent of rural surgeons
      were older than 50 years of age,  and 27.6 per cent of hospitals reported they
      would lose at least one surgeon in the next 2 years. The responding hospitals
      reported losing 10.4 per cent of their surgical workforce in the preceding 2
      years. Over 53 per cent were actively recruiting a general surgeon with an
      average time to  recruit a surgeon of 11.8 months. Ninety-seven per cent stated
      that having a surgical program was very important to their financial viability
      with the mean and median reported revenue generated by a single general surgeon
      being $1.8 million and $1.4 million, respectively. Almost  11 per cent of the
      hospitals stated they would have to close if they lost surgical services.
      Although rural Tennessee hospitals face similar difficulties to national rural
      hospitals with regard to retaining and hiring surgeons, slightly more Tennessee
      hospitals (54 vs 36%) were actively  attempting to recruit a general surgeon. The
      shortage of general surgeons is a threat to the accessibility of comprehensive
      hospital-based care for rural Tennesseans.

PMID- 21944342
TI  - Geriatric education for surgical residents: identifying a major need.
AB  - This study evaluated a program designed to test and enhance residents' knowledge
      of geriatrics. A 2-year prospective interventional trial was conducted. Surgical
      residents underwent pretesting (pre) in three areas: polypharmacy, delirium, and
      end of life. They then received educational  materials and completed a posttest
      within 1 month and a patient simulation examination graded by a physician
      observer and the patient on his or her satisfaction. Forty-nine residents (51%
      interns, 55% general surgery residents) participated. Seventy per cent had no
      prior geriatrics education.  Test scores significantly improved from pretest to
      posttest (12.9 +/- 3.1 vs 13.78 +/- 3.12, P = 0.01). The scores were consistently
      better on poly topics and consistently worse on end-of-life topics: pretest per
      cent correct: polypharmacy 60, end of life 46, P  = 0.007; posttest percent
      correct: polypharmacy 63, end of life 49, P = 0.0014. By Pearson correlation, the
      pretest and posttest scores did not correlate with either the observer (R = 
      0.16, P = 0.27 pre, R = -0.08, P = 0.59 post) or subscores  (R = -0.27, P = 0.11
      pre, R = -0.13, P = 0.45 post), although the observer and subscore correlated
      with each other (R = 0.35, P = 0.036). Performance was poor and did not correlate
      with better patient care by simulation. Other options for  geriatric education
      need to be considered and evaluated.

PMID- 21944343
TI  - Outcomes of revascularized acute mesenteric ischemia in the American College of
      Surgeons National Surgical Quality Improvement Program database.
AB  - This report examines outcomes of revascularization for acute arterial mesenteric
      ischemia (AAMI) using the American College of Surgeons National Surgical Quality
      Improvement Program database. Patients with International Classification of
      Diseases, 9th Revision and Current Procedural  Terminology codes indicating AAMI
      with concomitant mesenteric revascularization were identified. Demographic, risk
      factor, procedural, morbidity, and mortality data were examined. Associations
      with morbidity and mortality were analyzed by logistic regression. One hundred
      forty-two cases of  AAMI were identified. Seventy-one cases were thrombotic and
      71 were embolic according to revascularization codes. Mean age was 66 years, 84
      per cent of patients were white, and 54 per cent were female. Unadjusted major
      morbidity and mortality rates were 69 and 30 per cent, respectively. Patients 
      with thrombotic AAMI were more likely to have a lower body mass index, greater
      than 10 per cent weight loss in the past 6 months, and a history of smoking.
      Patients with embolic AAMI were more likely to present emergently with sepsis.
      Unadjusted morbidity and mortality rates were 78 and 38  per cent for embolic and
      61 and 23 per cent for thrombotic AAMI, respectively. Multivariable predictors of
      morbidity included bowel resection at the time of revascularization, transfer
      admission, and involvement of a surgical resident. Multivariable predictors of
      mortality included impaired  functional status, increased age, and postoperative
      sepsis. Cause of AAMI was not a significant predictor of morbidity or mortality.
      In a large sample of AAMI cases, AAMI remained a highly lethal and morbid
      condition. Predictors of morbidity and mortality included indicators of advanced
      presentation,  treatment delay, and patient-related factors specific to AAMI,
      including debility and advanced age. Efforts directed at prevention and
      increasing the speed of diagnosis and definitive treatment appear to be necessary
      to improve outcomes.

PMID- 21944344
TI  - The component separation technique for hernia repair: a comparison of open and
      endoscopic techniques.
AB  - The open components separation technique (CST) for hernia repair allows for
      autologous tissue repair with approximation of the midline fascia in patients
      with complex hernias. CST requires creation of large undermining skin flaps,
      whereas the endoscopic component separation technique  (ECST) is performed
      without division of the epigastric perforating vessels and may minimize wound
      morbidity. A review of patient demographics and outcome measures of patients
      undergoing CST and ECST between November 2008 and February 2010 was performed.
      Twenty-five patients were identified  who underwent either CST (14 patients) or
      ECST (11 patients). There were no differences in body mass index (CST 34.8
      kg/m(2), ECST 37.5 kg/m(2), P = 0.45), operating room times (CST 268 minutes,
      ECST 252 minutes, P = 0.54), or hospital length of stay (CST 5  days, ECST 5.8
      days, P = 0.78). Wound complications occurred less with ECST (9 vs 57%, P =
      0.03). The time to resolution of wound complications in ECST was reduced *1 vs 4
      months). No recurrences were seen in either group with a mean follow-up of
      4months (range,  1 to 12 months). ECST and CST require similar operative times
      and hospital lengths of stay. ECST is associated with reduced wound complications
      compared with CST. Short-term recurrence rates with CST and ECST are comparable.

PMID- 21944345
TI  - Gender-based analysis of perioperative outcomes associated with lower extremity
      bypass.
AB  - We analyzed gender-based differences in preoperative factors, procedural
      characteristics, and 30-day outcomes after lower extremity bypass (LEB). LEB
      procedures were identified from the American College of Surgeons National
      Surgical Quality Improvement Program Participant User File.  Groupwise
      comparisons of preoperative and procedural variables were made using chi square,
      t tests, and nonparametric methods; gender influences on mortality, systemic, and
      surgical site complications were evaluated using logistic regression. Women
      (4,107 of 11,011 [37.3%]) were older  and had greater prevalence of hypertension,
      diabetes, chronic obstructive pulmonary disease, rest pain, dialysis, previous
      stroke, open/infected wound, and dependent functional status (P < 0.01 for all
      comparisons). Women more commonly underwent emergent and extra-anatomic
      procedures  but had lower rates of venous conduit or tibial level outflow use.
      Univariable associations between female gender and risk of 30-day mortality,
      systemic, and surgical site complications were identified; only the association
      with surgical site complications remained significant in multivariable  modeling
      (OR, 1.8; 95% CI, 1.6 to 2.1; P < 0.0001). Gender-based differences in
      demographic, comorbidity, and procedural factors may contribute to disparities in
      perioperative outcomes associated with LEB. Female gender may be associated with
      increased risk for surgical site complications,  but 30-day mortality and
      systemic complication rates in women may reflect effects of confounding factors
      rather than gender-specific influence.

PMID- 21944347
TI  - Advanced age may limit the survival benefit of open abdominal decompression.
AB  - Open abdominal decompression (OAD) and temporary abdominal closure (TAC) are
      widely performed for the treatment of intra-abdominal hypertension and/or
      abdominal compartment syndrome. During 2005 to 2009, 405 consecutive patients
      required OAD/TAC (trauma 68%, surgery 24%, medicine 5%,  burn 3%). Overall
      patient survival to hospital discharge was 65 per cent regardless of age and was
      significantly decreased among patients older than 70 years of age (P < 0.0001).
      Survival by decade of life exceeded 50 per cent through the eighth decade but
      decreased to 19 per cent  for the ninth decade (older than 80 years of age).
      Survival varied significantly by service (trauma 72%, surgical 56%, burns 55%,
      medical 33%) (P < 0.0001). Successful definitive fascial closure rates (range, 75
      to 100%) were equivalent among all age groups (P = 0.78). Survival  after OAD/TAC
      varies by decade of life and mechanism of injury/illness. Age alone should not
      negate the use of OAD/TAC. Reasonable survival rates may be expected for patients
      younger than 80 years of age.

PMID- 21944346
TI  - Young women with locally advanced breast cancer who achieve breast conservation
      after neoadjuvant chemotherapy have a low local recurrence rate.
AB  - Women with locally advanced breast cancer (LABC) who are breast conservation
      (BCT) candidates after neoadjuvant chemotherapy have the best long-term outcome
      and low local-regional recurrence (LRR) rates. However, young women are thought
      to have a higher risk of LRR based on historical  data. This study sought to
      evaluate LRR rates in young women who undergo BCT after neoadjuvant chemotherapy.
      We identified 122 women aged 45 years or younger with American Joint Committee on
      Cancer (AJCC) Stage II to III breast cancer, excluding T4d, treated with
      neoadjuvant chemotherapy from  1991 to 2007 from a prospective, Institutional
      Review Board-approved, single-institution database. Data were analyzed using
      Fisher eExact test, Wilcoxon tests, and the Kaplan-Meier method. Median follow-up
      was 6.4 years. Fifty-four (44%) patients had BCT and 68 (56%) mastectomy. Forty
      six  per cent were estrogen receptor-positivity and 28 per cent overexpressed
      Her2. Mean pretreatment T size was 5.6 cm in the BCT group and 6.7 cm in the
      mastectomy group (P = 0.04). LRR rates were no different after BCT compared with
      mastectomy (13 vs 18%, P = 0.6). Higher  posttreatment N stage (P < 0.001) and
      AJCC stage (P = 0.008) were associated with LRR but not pretreatment staging.
      Disease-free survival was better for patients achieving BCT, with 5-year disease
      free survival rates of 82 per cent (95% CI, 69 to 90%) compared with 58 per  cent
      (95% CI, 45 to 69%) for mastectomy (P = 0.03). Young women with LABC who undergo
      BCT after neoadjuvant chemotherapy appear to have similar LRR rates compared with
      those with mastectomy. This suggests that neoadjuvant chemotherapy may identify
      young women for whom BCT may have an  acceptable risk of LRR.

PMID- 21944348
TI  - Differences in morbidity and mortality with percutaneous versus open surgical
      drainage of postoperative intra-abdominal infections: a review of 686 cases.
AB  - Intra-abdominal infections following surgical procedures result from organ-space
      surgical site infections, visceral perforations, or anastomotic leaks. We
      hypothesized that open surgical drainage is associated with increased patient
      morbidity and mortality compared with percutaneous  drainage. A single
      institution, prospectively collected database over a 13-year period revealed 2776
      intra-abdominal infections, 686 of which required an intervention after the index
      operation. Percutaneous procedures (simple aspiration or catheter placement) were
      compared with all other open  procedures by univariate and multivariate analyses.
      Analysis revealed 327 infections in 240 patients undergoing open surgical
      drainage and 359 infections in 260 patients receiving percutaneous drainage.
      Those undergoing open drainage had significantly higher Acute Physiology Score
      (APS) and  Acute Physiology and Chronic Health Evaluation (APACHE) II scores and
      were more likely to be immunosuppressed, require intensive care unit treatment,
      and have longer hospital stays. Mortality was higher in the open group: 14.6
      versus 4.2 per cent (P = 0.0001). Variables independently  associated with death
      by multivariate analysis were APACHE II, dialysis, intensive care unit (ICU)
      care, age, immunosuppression, and drainage method. Open intervention for
      postsurgical intra-abdominal infections is associated with increased mortality
      compared with percutaneous drainage even  after controlling for severity of
      illness by multivariate analysis. Although some patients are not candidates for
      percutaneous drainage, it should be considered the preferential treatment in
      eligible patients.

PMID- 21944349
TI  - Hepatic arterial therapy as a bridge to ablation or transplant in the treatment
      of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a challenging malignancy as a result of the
      advanced course at presentation. Recent interventional advances have improved
      treatment of lesions unamenable to resection using drug-eluting microbeads
      delivered into the hepatic circulation. We hypothesize  that the use of hepatic
      arterial therapy (HAT) will safely identify appropriate patients who can proceed
      to ablation and/or transplantation. We evaluated our open-label, multicenter,
      multinational, single-arm study including 240 patients with intermediate-staged
      HCC who received drug-eluting  beads and were not initial candidates for
      transplantation or resection. We reviewed the resulting clinical data to
      determine factors leading to possible ablation or transplant. Of 240 patients
      undergoing HAT, 14 (5.8%) received ablation or transplant. We compared those
      receiving ablation or  transplant with those receiving only HAT. Groups were
      similar regarding sex, age, median number of tumors (one; range, 1 to 25),
      Child's score, tobacco and alcohol abuse, and treatment type. Patients who were
      downstaged were more likely to have: hepatitis-related tumors (76 to 66%, P  =
      0.02), distinct lesions on imaging (92 to 76%, P = 0.004), and less than 25 per
      cent parenchymal involvement (84 to 59%, P = 0.0001). These patients typically
      had one tumor frequently in the left lobe (58.8 vs 30.9%, P = 0.0001), accessible
      through segmental arteries  (47 vs 17%, P = 0.001), with increased segmental
      branch occlusion (57 vs 39%, P = 0.02). HAT should be considered a potential
      bridging therapy to eventual ablation or transplant in the multimodal treatment
      of HCC.

PMID- 21944350
TI  - The impact of lymphovascular invasion on lymph node status in patients with
      breast cancer.
AB  - Lymphovascular invasion (LVI) is not uniformly found or reported in breast cancer
      tumor reports. We sought to determine the impact of the finding of LVI on various
      parameters of lymph node status in patients with breast cancer. A chart review
      was performed of 400 node-positive patients  from a cohort of patients in a
      prospective multicenter national sentinel node registry. The finding of LVI was
      then correlated to number of positive sentinel nodes, the number of positive
      nonsentinel nodes, the lymph node ratio, and the size of the largest metastatic
      deposit. Of the 400 patients,  data regarding LVI were missing in 98 (24.5%)
      cases. Although all of these patients were node-positive, LVI was noted to be
      present in 155 patients (38.8%) and absent in 147 (36.8%). LVI was found to
      correlate with more positive sentinel nodes (mean, 1.72 vs 1.35; P < 0.001), 
      more positive nonsentinel nodes (mean, 2.16 vs 0.54; P < 0.001), and a higher
      lymph node ratio (0.29 vs 0.16; P < 0.001). LVI also correlated with size of
      largest metastatic deposit (P = 0.002). Although LVI is known to be associated
      with lymph node  status, it is not frequently noted on pathology reports. Given
      its prognostic value, LVI should be carefully evaluated and reported.

PMID- 21944351
TI  - Impact of Nissen fundoplication on laryngopharyngeal reflux symptoms.
AB  - The reliability of Nissen fundoplication for the successful treatment of
      laryngopharyngeal reflux (LPR) symptoms remains in question. The purpose of this
      study was to assess the effect that antireflux surgery has on a variety of LPR
      symptoms as well as the patient's perceived success  of surgical intervention. A
      retrospective review of all antireflux surgeries between 1998 and 2008 provided a
      patient base for a survey in which patients ranked pre- and postoperative LPR
      symptoms in addition to patient satisfaction with the outcome. Of the 611
      patients identified and sent  the evaluation forms, 244 responses (40%) were
      obtained. The percentage of patients with symptom improvement after surgery were:
      heartburn (90.1%), regurgitation (92.6%), voice fatigue (75.2%), chronic cough
      (76.3%), choking episodes (83.1%), sore throat (82.9%), lump in throat (77.4%),
      repetitive  throat clearing (72.8%), and adult-onset asthma (59.6%). Twenty per
      cent with repetitive throat clearing and 30 per cent with adult-onset asthma had
      no improvement in symptoms. Eighty-one per cent considered surgery to be a
      success. Comparison of those who claimed the operation was successful  with those
      who claimed it was not revealed no difference in demographics, primary diagnosis,
      procedure type, or reflux symptom index score. There was a statistically
      significant difference in patient-perceived outcome according to the length of
      time since surgery. More than 88 per cent in  the "not successful" group had an
      operation greater than 4 years prior as compared with only 70 per cent in the
      "successful" group (P = 0.020). Nissen fundoplication is an effective treatment
      for most LPR symptoms, although patients with adult-onset asthma and  repetitive
      throat clearing appear to benefit least from surgical intervention.

PMID- 21944352
TI  - Quality of documented consent for the de-escalation of care on a general and
      trauma surgery service.
AB  - Postoperative and posttrauma mortality in the acute care setting often occurs
      after a decision for de-escalation of care. It is important that the quality of
      consent for de-escalation of care is maintained to ensure patient autonomy. This
      retrospective review aims to determine the quality  of the consent process for
      care de-escalation in patients on a trauma and general surgery service who
      sustained in-hospital mortality. One hundred thirty-three patients (99 trauma)
      were identified who died in 1 year. Of these patient deaths, 80 (60%) involved de
      escalation of care. In three  (3%) cases, there were no documented discussions
      for de-escalation consent. Of the remaining cases, documentation was considered
      optimal 21 per cent of the time. Only nine (11%) patients were able to
      participate in a discussion of their end-of-life care. The other 23 patients who
      were initially  competent lost their ability to participate in discussions after
      a debilitating event. In this study, the majority of patients who died on a
      surgical service underwent a de-escalation of care. The documentation quality was
      suboptimal in most cases. Earlier and more thorough discussion of the  patient's
      end-of-life wishes may improve the de-escalation of care consent process.

PMID- 21944353
TI  - Application of subcutaneous talc in hernia repair and wide subcutaneous
      dissection dramatically reduces seroma formation and postoperative wound
      complications.
AB  - Wound complications after large ventral hernia repairs when combined with wide
      subcutaneous dissection (OVHR/WSD) are common (33 to 66%). We evaluate a novel
      technique of applying talc to wound subcutaneous tissues to decrease wound
      complications. We accessed our prospectively collected  surgical outcomes
      database for OVHR/WSD procedures performed. Patients were divided into those that
      did and did not receive subcutaneous talc (TALC vs NOTALC). Demographics
      intraoperative and outcomes data were collected and analyzed. The study included
      180 patients (n = 74 TALC, n  = 106 NOTALC). Demographics were all similar, but
      hernias were larger in the TALC group. TALC patients had their drains removed
      earlier (14.6 vs 25.6 days; P < 0.001) with dramatic reduction in postoperative
      seromas requiring intervention (20.8 to 2.7%; P < 0.001)  and cellulitis (39.0 to
      20.6%; P = 0.007). Short-term follow-up demonstrates significantly higher
      recurrence rates in the NOTALC group with each recurrence related to infection.
      The use of talc in the subcutaneous space of OVHR/WSD results in significantly
      earlier removal of subcutaneous  drains, fewer wound complications, and a
      decrease in early hernia recurrence. Use of talc in the subcutaneous space at the
      time of wound closure is an excellent technique to decrease wound complications
      in large subcutaneous dissections.

PMID- 21944354
TI  - Neoadjuvant chemotherapy's role in triple negative breast cancer.
AB  - Neoadjuvant chemotherapy (NC) facilitates breast conservation in women with large
      tumors, which are common in our inner city breast clinic. We performed this
      review of our NC breast cancer experience, which includes a disproportionate
      number of triple negative patients. Patients treated  with NC were divided into
      two groups based on their tumor's receptor status. Patients with tumors negative
      for estrogen, progesterone, and HER2-neu were considered triple negative (TN) and
      patients with positive staining for any of these receptors were considered
      nontriple negative (NTN).  Response to NC was considered a complete response (CR)
      if no residual tumor was detected at surgery, partial response (PR) if the height
      and width was reduced by at least 50 per cent, and no response (NR) for anything
      less than a PR. Differences were assessed by chi(2) analysis  and Student's t
      test. We identified 30 patients treated with NC (11 TN and 19 NTN). Twenty-one
      patients (70%) were African American (11/11 TN and 10/19 NTN; P = 0.01). Age
      (46.8 +/- 6.0 years TN vs 49.5 +/- 11.7 years NTN), response rates (18% NR, 55%
      PR, and  27% CR TN; 37% NR, 42% PR, and 21% CR NTN), and node positivity (64% TN
      vs 74% NTN) were statistically similar. Two TN (20%) and seven (41%) NTN patients
      underwent breast conservation therapy. Our results demonstrate the association of
      African American race and TN breast cancer. TN  cancers respond similarly to NC
      when compared with NTN, allowing for tumor downstaging and possible breast
      conservation surgery.

PMID- 21944355
TI  - Appendicitis, is it an emergency?
AB  - Prompt appendectomy has always been a standard of care because of the risk of
      progression in pathology. This time honored practice has been recently challenged
      by studies, suggesting that appendicitis can be operated on electively. The aim
      of this study is to examine whether delayed  intervention in acute appendicitis
      is safe by correlating the interval from presentation to operation with the
      operative and postoperative complications. Retrospective review of patients who
      underwent appendectomy for acute appendicitis in 2009 was done. The following
      parameters were recorded:  demographics, duration from presentation to evaluation
      by emergency room attending, performing CT scan, surgical consult, and operation.
      The pathology, post operative complications, and length of stay were also
      recorded. Patients were divided into two groups: incision time < 10 hours (early 
      group) and incision time > 10 hours (delayed group). The end points chosen for
      comparison were: 1) laparoscopic to open conversion rate, 2) complications, 3)
      readmissions, and 4) length of stay. Number of cases totaled 201, with 76 in the
      < 10 hours group and 125 in the > 10 hours  group. The male to female ratio for
      the < 10 hours group was 54:22 and for the > 10 hours group was 59:66 (P <
      0.001). Length of stay for the early group was 75.52 hours and for the delayed
      group, 89.15 hours (P = 0.04). There was one intra-abdominal abscess in the early
      group and 10 in the delayed group (P = 0.04). The early group had 0.2 (2.6%)
      open conversions, and the delayed group had five (4.1%) conversions (P = 0.58).
      There were six (4.8%) readmissions in the delayed group and none in the early
      group (P = 0.05). Our study reveals  that the complication rate, length of stay,
      and readmissions are more in the delayed group. Conversion rate was more in the
      delayed group, but the difference was not significant. We conclude that early
      surgical intervention is beneficial in acute appendicitis.

PMID- 21944356
TI  - Minimally invasive training during surgical residency.
AB  - The field of postgraduate minimally invasive surgery training has undergone
      substantial growth and change. A survey was sent to all program directors in
      surgery. Minimally invasive training patterns, facilities, their views, and
      performance of residents were examined. Ninety-five directors  (38%) responded to
      the questionnaire. Of these, 51 per cent (n = 48) had a program size of three to
      four residents and 33 per cent (n = 31) had a program size of five to six
      residents. In 3 per cent of programs (n = 3), residents could not achieve the
      minimum Accreditation Council for Graduate  Medical Education required numbers
      for advanced laparoscopic cases. Only 47 per cent of programs (n = 45) had
      dedicated rotations in minimally invasive surgery, ranging from 2 to 11 months.
      Up to 10 per cent (n = 9) of program directors felt that the current training in
      minimally invasive  surgery was insufficient. Fifty-five per cent (n = 52) felt
      that laparoscopic adhesiolysis was an advanced laparoscopic procedure, and 33 per
      cent (n = 31) felt that there should be a separate minimum requirement for each
      of the commonly performed basic and advanced laparoscopic cases by Accreditation 
      Council for Graduate Medical Education. Fifty-six per cent (n = 53) of programs
      were performing robotic surgery. Minimally invasive surgery training for surgical
      residents needs to increase opportunities so that they are able to perform
      laparoscopic procedures with confidence. There should  be specific number
      requirements in each category of individual basic and advanced laparoscopic
      procedures.

PMID- 21944357
TI  - Does protected research time during general surgery training contribute to
      graduates' career choice?
AB  - A number of general surgery training programs offer a dedicated research
      experience during the training period. There is much debate over the importance
      of these experiences with the added constraints placed on training surgeons
      including length of training, Accreditation Council of  Graduate Medical
      Education limitations, and financial barriers. We seek to quantify the impact of
      a protected research experience on graduates of a university-affiliated general
      surgery training program. We surveyed all graduates of a single university
      affiliated general surgery training program  who completed training from 1989 to
      1999. Data was obtained for 100 per cent of the subjects. Most graduates (72/73;
      98.6%) completed a dedicated research experience (range: 1-5 years). Presently,
      72.6 per cent (53/73) are practicing academic surgery and 82.5 per cent (60/73)
      are engaged  in research activities. Fifty-one of 73 graduates (69.5%) have
      current research funding including 32.9 per cent (24/73) with National Institutes
      of Health funding. Of all graduates, 42.5 per cent (31/73) have become full
      professors with 20.2 per cent (15/73) division/section chiefs and 14.3  per cent
      (10/73) department chairmen or vice chairmen. Those trainees achieving a career
      in academic surgery were statistically more likely to have committed 2 or more
      years to a protected research experience during training (P < 0.05), fellowship
      training after general surgery residency  (P < 0.01), and a first job at an
      academic institution upon completion of training (P < 0.001). Understanding the
      importance of resident research experiences while highlighting critical factors
      during the formative training period may help to ensure continued academic
      interest  and productivity of future trainees.

PMID- 21944358
TI  - Laparoscopic living kidney donation at a single center: an examination of donor
      outcomes with increasing experience.
AB  - This study was undertaken to examine short-term outcomes of laparoscopic donor
      nephrectomy performed by transplant surgeons at a medium volume institution, with
      the specific goal of determining the presence of a learning curve effect. With
      institutional review board approval, a retrospective  chart review was performed
      examining patient demographics, operative factors, and in-hospital outcomes over
      a 12-year period. Specific attention was paid to differences in outcomes between
      patients undergoing operation in the first versus the most recent 6-year period.
      Continuous and  categorical variables were examined using the Wilcoxon rank sum
      test and chi(2) analysis, respectively. The study group consisted of 129
      patients. Median operative time was 234 minutes with a median estimated blood
      loss of 100. The median preoperative creatinine was 0.9, with a  postoperative
      median creatinine of 1.3. The overall complication rate was 12.4 per cent, with
      ileus being the most common. There were two cases of post op acute renal failure,
      both of which were self limited and did not require dialysis. No patients died.
      Patients in the most recent 6 years  (n = 77) enjoyed a shorter length of stay (2
      vs 3 days, P < 0.001) than patients in the first 6-year period (n = 52).
      Additionally, there was a trend towards decreased complications in the second era
      that did not reach significance (9.1% vs 17.3%, P = 0.17).  Laparoscopic donor
      nephrectomy is an attractive means of donation, and can be performed with low
      risk to the donor and minimal learning curve effect.

PMID- 21944359
TI  - Single incision laparoscopic cholecystectomy using a "two-port" technique is safe
      and feasible: experience in 101 consecutive patients.
AB  - Single incision laparoscopic cholecystectomy (SILC) is a new minimally-invasive
      technique that has recently been developed to address several disease processes
      of the gallbladder. However, the safety and feasibility of this technique are
      still being evaluated. Utilizing a "two-port"  technique with transabdominal
      suture retraction and a rigorous adherence to the critical view of safety, we
      evaluated our experience in a prospectively maintained database and compared this
      with standard laparoscopic cholecystectomy (SLC) over the same period. SILC was
      completed successfully  in 87 per cent of patients. Operative times were found to
      be similar between SLC and SILC (75 and 76 minutes, respectively; P = 0.12).
      Operative blood loss, hospital stay, and short-term complications were not
      statistically different between SILC and SLC. Cholangiograms, obtained on  a
      selective basis, were performed in 19 per cent of SILCs. No bile duct injuries
      occurred during SILC or SLC. Although our aggregate number is not enough to
      accurately assess the rate or safety of bile duct injuries, SILC seems to be safe
      and feasible when evaluating other metrics and does  not seem to interfere with
      operative efficiency compared with SLC.

PMID- 21944361
TI  - Incisionless laparoscopic total proctocolectomy with ileal J-pouch anal
      anastomosis.
AB  - Minimally invasive surgery continues to evolve. Recent innovations have included
      single-incision access, robotic technology, and natural orifice dissection and/or
      specimen extraction. Many argue that there is minimal patient benefit to these
      advanced techniques. We report 39 patients  undergoing laparoscopic ileal J-pouch
      anal anastomosis surgery, 17 of whom did not have a separate specimen extraction
      incision (Group 1). The specimen for this group was extracted through the
      circular incision made for the ileostomy; the pouch was constructed
      extracorporeally and returned  to the abdomen through the stoma site. For the
      remaining 22 patients, a suprapubic Pfannenstiel incision was made (Group 2). No
      hand-assistance was used for either group. Group 1 showed a 45-minute reduction
      in operative time, a 1-day reduction in hospital stay, and a reduction in
      complications.  Although these differences are modest, it shows that minimally
      invasive surgery is an evolving process. Small modifications may translate into
      significant advantages.

PMID- 21944362
TI  - Geographical influence on racial disparity in breast cancer presentation in the
      United States.
AB  - Breast cancer is the most commonly diagnosed cancer and the second leading cause
      of cancer death among women in the United States. It has been shown that breast
      cancer presentation varies between racial groups nationwide. Several studies have
      suggested that this is more a function of  geographic rather than true racial
      disparity. The current study was undertaken to examine racial disparity in breast
      cancer presentation and to determine whether such disparity continues to be seen
      once geographic factors are taken into account. Breast cancer data were reviewed
      for all programs  reporting to the American College of Surgeons Commission on
      Cancer National Cancer Database (NCDB) between 2000 and 2007, inclusive. These
      data were readily available online. Variables reviewed were: stage at the time of
      presentation; race; histology; and geographic location within the United  States.
      Four broad regions of the country were chosen, corresponding to the U.S. Census
      Regions: Northeast, South, Midwest, and West. Patient data were classified as
      either "early" (stages 0, I, and II) or "late" (stages III and IV) at the time of
      presentation. A total  of 1,388,186 patients were reported during the study
      period; 1,132,128 white and 256,058 nonwhite. There was a statistically
      significant difference in presentation between the two racial cohorts; a
      significantly higher percentage of whites presented with "early" disease (88.8%) 
      when compared with nonwhites (83.8%). This statistically significant difference
      persisted even when the data were corrected for geographic location within the
      United States. There is a racial disparity with regard to breast cancer
      presentation throughout the United States which seems to be  independent of
      geographic location. Nonwhites in all geographic regions present with later-stage
      disease than whites.

PMID- 21944363
TI  - Robotic Swenson pull-through for Hirschsprung's disease in infants.
AB  - It has been demonstrated that infants with Hirschsprung's disease can be treated
      with a one-stage laparoscopic resection and coloanal pull-through. However, the
      feasibility and benefits of performing this operation using robotic technology
      have not yet been evaluated. We reviewed our  experience with 12 infants
      diagnosed with Hirschsprung's disease and treated with laparoscopic-robotic
      assisted colonic resection with proctectomy and pull-through using the da Vinci
      robotic system. Patients were treated at a mean age/weight of 16 weeks/5.5 kg.
      The average operative time for  the robotic procedure was 230 minutes, and
      average length of stay was 3 days. At discharge, all patients were having regular
      bowel movements and tolerating a completely oral diet. All patients received
      early postoperative anorectal dilation and six patients required dilations for an
      average  of 12 weeks after surgery for management of minor rectal strictures.
      Only two patients developed postoperative enterocolitis with a mean follow-up of
      36 months. A robotic approach for performing a Swenson-type resection and pull
      through procedure can be performed safely and successfully in  young infants.
      Robotic technology provided superior dexterity and visualization, essential in
      performing a more complete rectal dissection, thus allowing for a complete
      proctectomy and eliminating the risk of leaving a segment of aganglionic rectum
      behind.

PMID- 21944360
TI  - Surgical skin markers impair human saphenous vein graft smooth muscle and
      endothelial function.
AB  - Marking human saphenous vein graft (HSV) with a surgical skin marker to prevent
      twisting on implantation is a common practice in peripheral and coronary artery
      bypass procedures. This study is designed to examine the effects of surgical skin
      markers on the HSV smooth muscle and endothelial  functional responses. De
      identified HSV remnants were collected during peripheral and coronary artery
      bypass procedures. Physiologic responses of the HSV were measured using a muscle
      bath. Veins that were marked with surgical skin markers intraoperatively
      generated significantly less contractile  force to depolarizing KCl (110 mM) and
      receptor-mediated contractile agonists than unmarked HSV, suggesting that
      surgical skin markers impaired HSV smooth muscle contractility. To directly
      access the effects of chemical components in the surgical skin markers, unmarked
      HSV was exposed to isopropyl  alcohol (a solvent commonly used in surgical skin
      markers) or methylene blue (a dye). Smooth muscle contractility was significantly
      reduced by isopropyl alcohol and methylene blue. Endothelial-dependent relaxation
      to carbachol was significantly reduced after exposure to surgical skin markers. 
      Our data demonstrated that marking HSV with surgical skin markers reduces smooth
      muscle and endothelial functional viability.

PMID- 21944364
TI  - Predictors and outcomes of prolonged ventilation after coronary artery bypass
      graft surgery.
AB  - This study investigated and compared the risk factors and outcomes of patients
      undergoing coronary artery bypass graft surgery with and without the occurrence
      of prolonged mechanical ventilation. Data in a cardiac surgery database were
      examined retrospectively. Data selected included  any isolated coronary artery
      bypass graft surgery performed by the surgical group from August 2005 to June
      2009. The resulting cohort included a total of 2933 patients which was comprised
      of 116 patients with a ventilation time of greater than 72 hours (prolonged
      ventilation) and 2817 patients  with a ventilation time of 72 hours or less (no
      prolonged ventilation). Patients with a prolonged ventilation time were matched
      (1:3 ratio) to patients not requiring a prolonged ventilation time by year of
      surgery resulting in our study cohort of 464 patients. To generate the unadjusted
      risks  of each factor, chi(2) and t test analysis were performed. Logistic
      regression analysis was then used to investigate the adjusted risk between cases
      and controls and each of the significant variables. chi(2) and t tests were
      conducted comparing cases and  controls with the outcome variables. Patients
      undergoing coronary artery bypass graft that experienced a prolonged ventilation
      time (cases) were more likely female, had a New York Hospital Association
      functional class of III or IV, and had a longer perfusion time. There was no
      significant  difference between cases and controls with diabetes, chronic
      obstructive pulmonary disease, left ventricular ejection fraction, or body mass
      index while controlling for all significant risk factors. Careful patient
      selection and preparation during preoperative evaluation may help identify 
      patients at risk for prolonged mechanical ventilation and thus help prevent the
      added morbidity and mortality associated with it.

PMID- 21944365
TI  - The status of surgical skills training in the Carolinas: a plea for
      collaboration.
AB  - A paradigm shift is underway in the training of general surgery residents with
      emphasis placed on learning skills on simulators before patient encounters. To
      that end, national skills curricula have been proposed, but their adoption by
      regional programs is unknown. The purpose of this  study was to assess the
      adoption of surgical skills training in residency programs in North and South
      Carolina. Surveys were sent electronically to faculty members overseeing surgical
      skills training at the 10 residency programs in North and South Carolina. Surveys
      included seven questions  related to skills training implementation and allocated
      resources at each training program. Eight programs responded and all reported the
      existence of a formal skills curriculum with mandatory resident participation
      policies. Programs allotted from 0 to 8 hours of protected time per month  for
      skills training, but actual resident participation was less (0 to 4 hours). The
      type of skills curricula used varied among institutions and included time-based,
      proficiency-based, and the use of the national skills curriculum. Six programs
      (75%) had dedicated protected time for faculty  trainers and had hired personnel
      sponsored by the hospital/surgical department to assist with running the skills
      lab. Equipment and resources varied among institutions; all but one program
      reported receiving funding/resources from industry. Five programs reported they
      had active simulation  research protocols. Variability and lack of
      standardization exists with regard to surgical skills training in residency
      training programs in North and South Carolina. Collaborative efforts to promote
      standardization are needed and are presently underway.

PMID- 21944366
TI  - A critical assessment of outcomes in emergency versus nonemergency general
      surgery using the American College of Surgeons National Surgical Quality
      Improvement Program database.
AB  - Emergent operations are thought to carry higher morbidity and mortality than
      nonemergent cases. However, there is a lack of specific outcomes data for
      emergent general surgery procedures. The objective of our study was to assess and
      quantify postoperative morbidity and mortality for  emergency versus nonemergency
      general surgery operations. All general surgery inpatients were identified in the
      American College of Surgeons National Surgical Quality Improvement Program 2008
      database. Preoperative, intraoperative, and postoperative clinical metrics and
      occurrences  were assessed. A total of 25,770 emergent and 98,867 nonemergent
      cases were identified. Postoperative morbidity was significantly worse in the
      emergent group, including ventilation more than 48 hours, bleeding requiring
      transfusion, deep vein thrombosis, renal failure, and need for reoperation. 
      Overall, emergent cases had significantly more postoperative complications (22.8%
      vs 14.2%) and higher mortality rates (6.5% vs 1.4%). General surgery patients who
      undergo emergent operations have significantly poorer outcomes when compared with
      nonemergent patients; our analysis  has quantified these differences. Emergent
      patients seem to manifest unique clinical, pathophysiologic, and inflammatory
      responses to their surgical disease. This data suggests that there is a need for
      improvement in both methods and systems of care for the emergent population.

PMID- 21944367
TI  - Boot camp: a method of introducing the competency of professionalism to surgical
      residents.

PMID- 21944368
TI  - Single-site laparoscopic appendectomy: a comparison to traditional laparoscopic
      technique in children.

PMID- 21944369
TI  - Posterior dislocation of meniscal bearing insert in mobile bearing
      unicompartmental knee arthroplasty mimicking a Baker cyst.
AB  - Unicompartmental knee arthroplasty (UKA) is a well-established procedure for
      isolated medial compartment osteoarthritis. Meniscal dislocation is a well
      recognized complication in mobile bearing UKA especially when performed for the
      lateral compartment. Dislocation in medial UKA is relatively uncommon and is
      usually anterior when encountered. We would like to report a case of posterior
      dislocation of the bearing insert in a mobile bearing medial UKA presenting as a
      Baker cyst, which was subsequently revised to total knee arthroplasty.

PMID- 21944370
TI  - Conversion of fused hip to total hip arthroplasty with presurgical and
      postsurgical gait studies.
AB  - This case study presents a subject with a fused hip converted to total hip
      arthroplasty. Kinematic gait analysis was conducted on 3 occasions, presurgery, 4
      months postsurgery, and 2.5 years postsurgery. Presurgery data showed decreased
      cadence and shorter step length; sound limb possessed increased hip, knee range
      of motion (ROM), and increased knee flexion during stance; the affected limb had
      minimal hip motion and normal knee ROM with abnormal pattern. At 4 months
      postsurgery, the sound limb showed decreased step length, whereas the affected
      limb showed increased knee extension during stance and increased hip ROM. Data
      obtained at 2.5 years postsurgery indicated decreased cadence and speed and
      increased ROM in both limbs. The total hip arthroplasty had provided relief of
      chronic back and affected hip pain and improved mobility. Gait-specific training
      is recommended.

PMID- 21944371
TI  - A comparison of outcomes with and without a tourniquet in total knee
      arthroplasty: a systematic review and meta-analysis of randomized controlled
      trials.
AB  - A tourniquet is often used in total knee arthroplasty resulting in improved
      visualization of structures, reduced intraoperative bleeding and better
      cementation. The risks include deep vein thrombosis and pulmonary embolism. To
      quantify the case for or against tourniquet use, we carried out a systematic
      review and meta-analysis of selected randomized controlled trials. Ten studies
      were included in the meta-analysis. Of the 8 outcomes analyzed (surgery duration;
      total, intraoperative, and postoperative blood losses; deep vein thrombosis;
      pulmonary embolism; and minor/major complications), the total and intraoperative
      blood losses were less using a tourniquet. Minor complications were more common
      in the tourniquet group. The remaining outcomes showed no difference between the
      groups. Using a tourniquet may be beneficial, but long-term studies of outcome
      are needed.

PMID- 21944372
TI  - Hydroxyapatite block for reconstruction of severe dysplasia or acetabular bone
      defects in total hip arthroplasty: operative technique and clinical outcome.
AB  - Fourteen hips in 14 patients (all female; average age, 64 years) with severe bone
      defects due to developmental dysplasia of the hip or migration of the socket were
      treated with hydroxyapatite block with impacted morselized bone graft in
      conjunction with a cemented socket. All patients were followed clinically in a
      prospective fashion, and radiographs were analyzed retrospectively. One initial
      patient had 17-year follow-up, whereas the remaining 13 patients had follow-up
      between 4 and 6.5 years. No acetabular components were revised, including the
      socket of a 17-year postoperative case that remains rigidly fixed and supported
      by the graft and hydroxyapatite block with only mild polyethylene wear and minor
      osteolysis. Osteointegration and good clinical outcome were achieved in all cases
      by reconstruction with this technique in total hip arthroplasty.

PMID- 21944373
TI  - Reattachment of complex femoral greater trochanteric nonunions with dual locking
      plates.
AB  - The goal of this retrospective study was to evaluate complex nonunions of the
      trochanter fixed with dual locking plates after failed cable fixation devices.
      Fifteen consecutive patients were operated on for greater trochanteric nonunion
      and with a mean follow-up of 53.1 months (range, 26-88 months). Fixation was
      achieved with dual locking plates contoured on the anterolateral and
      posterolateral surface of the greater trochanter. Trochanteric union was achieved
      in 13 patients (87%). Failures occurred only when the trochanter was reattached
      to a proximal femoral allograft. The average total hip score was 14.8 +/- 2.2
      (Merle d'Aubigne ) and 77.6 (+/-12.8) (Harris Hip score). However, 20% of
      successful cases needed painful hardware removal. Greater trochanter nonunions
      can be successfully reattached with locking plates especially if bone-to-bone
      apposition is achieved at surgery.

PMID- 21944374
TI  - Effects of kneeling on tibiofemoral contact pressure and area in posterior
      cruciate-retaining and posterior cruciate-sacrificing total knee arthroplasty.
AB  - The objective of this study was to measure the effect of kneeling on tibiofemoral
      contact following cruciate-retaining and posterior-stabilized total knee
      arthroplasty. Five cadaveric knees were tested on a custom testing system that
      allowed physiologic muscle loading. Three forces were used to simulate
      nonkneeling, double-stance kneeling, and single-stance kneeling at flexion angles
      of 90 degrees , 105 degrees , 120 degrees , and 135 degrees . Tibiofemoral
      contact areas and pressures were measured using the Tekscan (South Boston, MA)
      system. Kneeling increased contact areas and pressures in both designs with
      variable significance (P < .05). Moving from double- to single-stance kneeling
      increased pressures in the cruciate-retaining group but decreased pressures in
      the posterior-stabilized group (P < .05). Chronic, repetitive kneeling after
      total knee arthroplasty may increase polyethylene wear due to increased contact
      areas and pressures.

PMID- 21944375
TI  - Inequality in early childhood: risk and protective factors for early child
      development.
AB  - Inequality between and within populations has origins in adverse early
      experiences. Developmental neuroscience shows how early biological and
      psychosocial experiences affect brain development. We previously identified
      inadequate cognitive stimulation, stunting, iodine deficiency, and iron
      deficiency anaemia as key risks that prevent millions of young children from
      attaining their developmental potential. Recent research emphasises the
      importance of these risks, strengthens the evidence for other risk factors
      including intrauterine growth restriction, malaria, lead exposure, HIV infection,
      maternal depression, institutionalisation, and exposure to societal violence, and
      identifies protective factors such as breastfeeding and maternal education.
      Evidence on risks resulting from prenatal maternal nutrition, maternal stress,
      and families affected with HIV is emerging. Interventions are urgently needed to
      reduce children's risk exposure and to promote development in affected children.
      Our goal is to provide information to help the setting of priorities for early
      child development programmes and policies to benefit the world's poorest children
      and reduce persistent inequalities.

PMID- 21944376
TI  - Early childhood development-global action is overdue.

PMID- 21944377
TI  - Purtscher-like retinopathy caused by acute pancreatitis.

PMID- 21944378
TI  - Strategies for reducing inequalities and improving developmental outcomes for
      young children in low-income and middle-income countries.
AB  - This report is the second in a Series on early child development in low-income
      and middle-income countries and assesses the effectiveness of early child
      development interventions, such as parenting support and preschool enrolment. The
      evidence reviewed suggests that early child development can be improved through
      these interventions, with effects greater for programmes of higher quality and
      for the most vulnerable children. Other promising interventions for the promotion
      of early child development include children's educational media, interventions
      with children at high risk, and combining the promotion of early child
      development with conditional cash transfer programmes. Effective investments in
      early child development have the potential to reduce inequalities perpetuated by
      poverty, poor nutrition, and restricted learning opportunities. A simulation
      model of the potential long-term economic effects of increasing preschool
      enrolment to 25% or 50% in every low-income and middle-income country showed a
      benefit-to-cost ratio ranging from 6.4 to 17.6, depending on preschool enrolment
      rate and discount rate.

PMID- 21944379
TI  - Co-expression of erythropoietin receptor with human epidermal growth factor 2 may
      counteract trastuzumab inhibition in gastric cancer.
AB  - Gastric cancer has high prevalence and high modality worldwide. For many years,
      few improvements in the efficacy of treatments were reported for advanced gastric
      cancer settings. Although a novel molecular target agent trastuzumab, in
      combination with chemotherapy, prolongs overall survival time in advanced gastric
      cancer, resistance to this drug still exists among human epidermal growth factor
      receptor-2 (HER2) positive patients. HER2 and erythropoietin receptor (EPOR)
      downstream signaling pathway have some common factors like Akt, Erk and STATs.
      Also there exist evidences that EPOR may express on some solid tumors and
      probably promote tumor progression. So it is reasonable for us to hypothesis that
      HER2 and EPOR may be co-expressed in the same gastric cancer cell and if so, EPOR
      signaling pathway may overlaps that with HER2 and promotes HER2 induced signal
      transduction to cell proliferation. In clinical settings, a stimulation of EPOR
      will play antagonistic effects on trastuzumab-induced anti-tumor activity to HER2
      positive gastric cancer patients. Co-expression of EPOR and HER2 is a predictive
      factor for resistance of trastuzumab in gastric cancer.

PMID- 21944380
TI  - [Strawberry tongue and red eyes].

PMID- 21944381
TI  - Steroidal C-21 mercapto derivatives as dissociated steroids: discovery of an
      inhaled dissociated steroid.
AB  - A series of C-21 mercapto derivatives of hydrocortisone have been synthesized and
      evaluated in cell based transrepression and transactivation assays. The
      benzothiazole derivative, compound 6 not only showed a dissociated profile in
      vitro functional assays but also a pharmacological profile in a Brown-Norway rat
      therapeutic index model of asthma that dissociated side effects (thymolysis)
      while maintaining efficacy against pulmonary inflammation and lung function.

PMID- 21944382
TI  - Unintentional extraction of a coronary stent deployed two months prior during a
      dislodged left main stent retrieval.

PMID- 21944383
TI  - Combined VEGF gene transfer and erythropoietin in ovine reperfused myocardial
      infarction.
AB  - BACKGROUND: In reperfused acute myocardial infarction (RAMI), cardioprotective
      treatments may enhance myocardial salvage and hence reduce the area of necrosis.
      Based on studies showing that plasmid-mediated vascular endothelial growth factor
      (pVEGF) gene transfer reduces infarct size by combining angio-arteriogenic and
      cardiomyogenic effects and that erythropoietin (EPO) exerts anti-apoptotic
      actions in animal models of AMI, we aimed to assess if their association would
      reduce infarct size to a larger extent than any of them individually in a large
      mammalian model of RAMI. METHODS: Adult sheep subjected to 90-minute coronary
      artery occlusion received upon reperfusion intramyocardial pVEGF 3.8 mg plus
      intravenous EPO 1000 IU/kg (n=8), pVEGF (n=8), EPO (n=8) or placebo (n=8).
      RESULTS: Fifteen days after treatment, infarct size was smaller in the 3
      treatment groups (pVEGF+EPO: 8 +/- 1 %; pVEGF: 16 +/- 5 %; EPO: 13 +/- 4 %)
      compared to placebo (25 +/- 7 %, p<0.001). However, in the EPO+VEGF group infarct
      size was significantly smaller than in the groups receiving EPO or VEGF
      individually (p<0.05). DNA fragmentation, a hallmark of late apoptosis, was
      significantly lower in sheep receiving EPO. The combined treatment, while not
      affecting global left ventricular performance, improved regional peri-infarct
      function and prevented over-time expansion of the post-infarct perfusion defect.
      CONCLUSIONS: Combined pVEGF and EPO treatment might be clinically useful to
      enhance the benefits of early revascularization in patients with acute myocardial
      infarction.

PMID- 21944384
TI  - Refinement of echocardiographic criteria for left ventricular noncompaction.
AB  - BACKGROUND: Left ventricular hypertrabeculation/noncompaction (LVNC) is a cardiac
      abnormality whose echocardiographic criteria are still controversial. Cooperation
      between echocardiographic laboratories may contribute to uniformly accepted
      criteria, as illustrated by the following pilot study. METHODS AND RESULTS:
      Echocardiograms proposed for inclusion into a registry were reviewed. Three
      experts with 17-26 years experience with LVNC agreed on a common definition of
      LVNC: 1. >3 prominent trabeculous formations along the left ventricular
      endocardial border visible in end-diastole, distinct from papillary muscles,
      false tendons or aberrant bands; 2. trabeculations move synchronously with the
      compacted myocardium, 3. trabeculations form the noncompacted part of a two
      layered myocardial structure, best visible at end-systole; and 4. perfusion of
      the intertrabecular spaces from the ventricular cavity is present at end-diastole
      on color-Doppler echocardiography or contrast echocardiography. During 3 sessions
      115 cases (37% females, mean 57 years) were reviewed. Eleven patients (18%
      females, mean 60 years) were excluded because of <4 trabeculations (n=5), lack of
      a two-layered myocardial structure (n=1) and poor image quality (n=5). The
      observers agreed on inclusion or exclusion in all cases. Consensus was achieved
      that measurements of the thickness of the myocardial layers, and calculation of
      the noncompacted:compacted ratio is not feasible due to a lack of uniformly
      accepted standards for measurements. CONCLUSIONS: When diagnosing LVNC, end
      systolic as well as end-diastolic images have to be considered. The presence of
      more than three trabeculations as well as a two-layered myocardium are required.
      Since these criteria are not anatomically controlled, a comparison of
      echocardiographic images with pathoanatomic findings for assessing sensitivity
      and specificity is urgently needed.

PMID- 21944385
TI  - [Bordetella holmesii bacteremia in a child with sickle cell disease].

PMID- 21944386
TI  - Colonic effects of drugs, toxins and herbals. Foreword.

PMID- 21944388
TI  - Method for the current review.

PMID- 21944390
TI  - Diarrhea.

PMID- 21944391
TI  - Constipation.

PMID- 21944389
TI  - Types of colitis based on histology.

PMID- 21944392
TI  - Other effects on the colon.

PMID- 21944393
TI  - Coevolutionary fine-tuning: evidence for genetic tracking between a specialist
      wasp parasitoid and its aphid host in a dual metapopulation interaction.
AB  - In the interaction between two ecologically-associated species, the population
      structure of one species may affect the population structure of the other. Here,
      we examine the population structures of the aphid Metopeurum fuscoviride, a
      specialist on tansy Tanacetum vulgare, and its specialist primary hymenopterous
      parasitoid Lysiphlebus hirticornis, both of which are characterized by
      multivoltine life histories and a classic metapopulation structure. Samples of
      the aphid host and the parasitoid were collected from eight sites in and around
      Jena, Germany, where both insect species co-occur, and then were genotyped using
      suites of polymorphic microsatellite markers. The host aphid was greatly
      differentiated in terms of its spatial population genetic patterning, while the
      parasitoid was, in comparison, only moderately differentiated. There was a
      positive Mantel test correlation between pairwise shared allele distance (DAS) of
      the host and parasitoid, i.e. if host subpopulation samples were more similar
      between two particular sites, so were the parasitoid subpopulation samples. We
      argue that while the differences in the levels of genetic differentiation are due
      to the differences in the biology of the species, the correlations between host
      and parasitoid are indicative of dependence of the parasitoid population
      structure on that of its aphid host. The parasitoid is genetically tracking
      behind the aphid host, as can be expected in a classic metapopulation structure
      where host persistence depends on a delay between host and parasitoid
      colonization of the patch. The results may also have relevance to the Red Queen
      hypothesis, whereupon in the 'arms race' between parasitoid and its host, the
      latter 'attempts' to evolve away from the former.

PMID- 21944394
TI  - Longitudinal cognitive assessment in healthy late preterm infants.
AB  - BACKGROUND: Longitudinal cognitive development in late preterm (LP) infants has
      not been previously evaluated, using structured assessments. AIM: To assess
      longitudinally cognitive development in a population of healthy LP infants from
      12 months to preschool age. METHODS: Sixty-two low-risk LP infants (33-36 weeks
      gestation) with normal or only minor findings on their cranial ultrasound scans
      were included in the study. They were assessed at 12 and 18 months corrected age
      using the Bayley Scales of Infant Development II to obtain the mental development
      index (MDI) and then at preschool age (mean age 62 +/- 7 months) using the
      Wechsler Preschool and Primary Scale of Intelligence (WPPSI-R). RESULTS: The MDI
      scores obtained at both 12 and 18 months corrected age were within the reported
      normative range. Using uncorrected ages, their scores were lower at both ages
      than those obtained using CA (p < 0.01). Full-scale IQ scores within the reported
      normal range were obtained at 5 years using the WPPSI-R for all but 6 children.
      Females had significantly higher scores than males (p < 0.001) for the MDI at
      both 12 and 18 months corrected and uncorrected age. No gender differences were
      found at preschool age using the WPPSI-R. CONCLUSIONS: Our results suggest that
      over 90% of the low-risk late preterms reach an MDI and IQ at preschool age
      within normal range.

PMID- 21944395
TI  - Internal fixation: a historical review.
AB  - Internal fixation has become a pillar of surgical specialties, yet the evolution
      of these devices has been relatively short. The first known description of
      medical management of a fracture was found in the Edwin Smith Papyrus of Ancient
      Egypt (circa 2600 bc). The first description of internal fixation in the medical
      literature was in the 18th century. The advancement of techniques and technology
      over the last 150 years has helped to preserve both life and function. The pace
      of advancement continues to accelerate as surgeons continue to seek new
      technology for osseous fixation. The authors present a thorough review of the
      history of internal fixation and the transformation into a multibillion dollar
      industry.

PMID- 21944396
TI  - Locking plate technology and its use in foot and ankle surgery.
AB  - This article discusses the history of conventional plating, plate biomechanics,
      and screw function to provide better understanding of osseous physiology and
      biology using locking plates. The peer-reviewed and non-peer-reviewed literature
      have been researched to decipher and share the most pertinent information on this
      topic.

PMID- 21944397
TI  - Advances in intramedullary nail fixation in foot and ankle surgery.
AB  - Tibiotalocalcaneal arthrodesis for the treatment of complex foot and ankle
      deformities are extremely challenging cases. Technological advances in
      intramedullary nail fixation have improved the biomechanical properties of
      available fixation constructs in recent years. Nails designed specifically to
      accommodate hindfoot anatomy, advancement in the understanding of optimal screw
      orientation, fixed angle technology, the availability of spiral blade screws, and
      features designed to achieve compression across the arthrodesis site have
      provided the foot and ankle surgeon with a greater armamentarium for performing
      tibiotalocalneal arthrodesis. Although advances may help to improve clinical
      results, small sample sizes and the low-level evidence of study designs limit the
      evaluation of how these advances affect clinical outcomes.

PMID- 21944398
TI  - External fixation techniques for plastic and reconstructive surgery of the
      diabetic foot.
AB  - Wound healing in high-risk patients with diabetes is often lengthy and fraught
      with complications. Techniques in plastic and reconstructive surgery of the
      diabetic foot continue to develop as a result of advances in external fixation.
      This article highlights the surgical aspect of the diabetic foot with an emphasis
      on the indications, advantages, technical pearls, and complications with use of
      external fixation as an adjunct to plastic and reconstructive surgery of the
      diabetic foot.

PMID- 21944399
TI  - Advanced foot and ankle fixation techniques in patients with diabetes.
AB  - This article presents advanced techniques and current fixation constructs that
      are advantageous for the management of diabetic foot and ankle trauma and Charcot
      neuroarthropathy. Both these pathologies are often intimately related, and the
      fixation constructs that are required often require sound biomechanical concepts
      coupled with innovative approaches to achieve bone healing and limb salvage.

PMID- 21944400
TI  - Internal fixation techniques for midfoot charcot neuroarthropathy in patients
      with diabetes.
AB  - Charcot neuropathic osteoarthropathy (CN) of the foot and ankle is a poorly
      understood destructive process that poses a great clinical challenge to foot and
      ankle specialists. Neuropathic fractures or dislocations in the foot and ankle
      predispose patients to increased morbidity, premature mortality, and can greatly
      decrease quality of life. Early recognition and treatment of CN is imperative to
      prevent the development of permanent deformities. The purpose of this article is
      to review the history, cause, and classification of CN and to discuss commonly
      used internal fixation techniques and their indications.

PMID- 21944401
TI  - Opening wedge and anatomic-specific plates in foot and ankle applications.
AB  - As surgeons continually push to improve techniques and outcomes, anatomic
      specific and procedure-specific fixation options are becoming increasingly
      available. The unique size, shape, and function of the foot provide an ideal
      framework for the use of anatomic-specific plates. These distinctive plate
      characteristics range from anatomic contouring and screw placements to
      incorporated step-offs and wedges. By optimizing support, compression, and
      stabilization, patients may return to weight bearing and activity sooner,
      improving outcomes. This article discusses anatomic-specific plates and their use
      in forefoot and rearfoot surgical procedures.

PMID- 21944402
TI  - Advancements in percutaneous fixation for foot and ankle trauma.
AB  - Operative fixation of foot and ankle trauma can be challenging. Often times, the
      soft tissue envelope can have extensive damage as a result of the fracture. In
      these cases, percutaneous fixation may be used. Percutaneous fixation can benefit
      both soft tissue and osseous healing when used correctly. Many techniques have
      been described in the literature that may help to preserve blood supply, minimize
      soft tissue dissection, and restore a functional limb. This article reviews
      general guidelines for fracture and soft tissue management, osseous healing of
      fractures, and how certain techniques influence fracture healing. It also
      illustrates certain techniques for specific fracture reduction.

PMID- 21944403
TI  - Total ankle replacements: an overview.
AB  - One of the most widely debated topics amongst foot and ankle surgeons is the
      treatment of end stage arthritis. With the advent of the newer generation of
      total ankle replacement (TAR), a viable option over an arthrodesis is now
      available for patients with end-stage ankle arthritis. When compared with an
      ankle arthroplasty, recent reports suggest the ankle arthrodesis has poor long
      term outcomes (20 years+) and can experience short- and long-term complications.
      Proper training, strict patient selection, and proper implant contribute to a
      successful outcome. As advances continue to be made in both implant design and
      surgical technique, the benefits of a TAR appears to provide the foot and ankle
      surgeon a good alternative for the appropriate patient.

PMID- 21944404
TI  - Subtalar arthroereisis.
AB  - Arthroereisis has gained popularity over the years because it eliminates
      excessive pronation while conserving preoperative inversion and preserves
      forefoot to rearfoot adaptation to uneven terain. Technically simple, some of the
      advantages of subtalar arthroereisis are that it is joint sparing and preserves
      ligaments. In addition, the implant does not interfere with osseous growth and
      does not compromise future operative intervention if more invasive procedures are
      required. Arthroereisis, however, can have associated complications along with
      the need for surgical removal in some patient populations.

PMID- 21944405
TI  - Total first metatarsophalangeal joint implant arthroplasty: a 30-year
      retrospective.
AB  - The first metatarsophalangeal (MTP) joint is a frequent diseased-affected
      articulation encountered by the foot and ankle surgeon. Arthroplasty remains a
      favorable option for surgeons, because it preserves motion of the joint. The
      authors' focus at the Weil Foot and Ankle Institute has been on using double-stem
      silicone implants with titanium grommets, which may be a viable solution for
      affected articulations. The authors present their clinical results from over 30
      years of experience with total first MTP joint implant arthroplasty at the Weil
      Foot and Ankle Institute.

PMID- 21944406
TI  - Transcalcaneal talonavicular dislocation associated with an open comminuted
      calcaneal fracture: a case report.
AB  - The combination of dorsal dislocation of the navicular from the talus and a
      comminuted fracture of the calcaneus (transcalcaneal talonavicular dislocation)
      is an unusual and severe injury. It occurs due to a forced plantarflexion of the
      talar head through the anterior portion of the calcaneum and is usually
      associated with a potential for skin and neurovascular compromise. Few cases have
      been reported in the literature. This article reports an unusual case of an open
      transcalcaneal talonavicular dislocation associated with the presence of a
      calcaneal comminuted calcaneal fracture.

PMID- 21944407
TI  - Digital arthrodesis: current fixation techniques.
AB  - Several hammertoe implant devices have recently been introduced in an attempt to
      provide optimal fixation for proximal interphalangeal joint arthrodesis. This
      article reviews these implants individually, and discusses their advantages and
      disadvantages. There is a lack of research with long-term follow-up available for
      these devices. Percutaneous Kirschner-wire fixation persists as a time-honored
      and effective method of fixation. The buried Kirschner-wire technique is also an
      effective, cost-conscious option, with many of the same advantages as newer
      implantable devices.

PMID- 21944410
TI  - Differential diagnosis of upper gastrointestinal bleeding proximal to the
      ligament of Trietz.
AB  - Upper gastrointestinal bleeding (UGIB) is an important medical problem for
      patients and the medical system. The causes of UGIB are varied and their accurate
      identification guides appropriate management. The major cause of UGIB is peptic
      ulcer disease, for which Helicobacter pylori and nonsteroidal antiinflammatory
      drug use are major risk factors. Lesser causes include Dieulafoy lesion, gastric
      antral vascular ectasia, hemobilia, aortoenteric fistulas, and upper
      gastrointestinal tumors. Awareness of causes and management of UGIB should allow
      physicians to treat their patients more effectively.

PMID- 21944411
TI  - Epidemiology and demographics of upper gastrointestinal bleeding: prevalence,
      incidence, and mortality.
AB  - Despite major advances in diagnosis, prevention, and treatment, nonvariceal upper
      gastrointestinal bleeding still is a serious problem in clinical practice.
      Current evidence indicates that most peptic ulcer bleeding-linked deaths are not
      a direct sequela of the bleeding ulcer itself. Instead, mortality derives from
      multiorgan failure, cardiopulmonary conditions, or terminal malignancy,
      suggesting that improving further current treatments for the bleeding ulcer may
      have a limited impact on mortality unless supportive therapies are developed for
      the global management of these patients.

PMID- 21944412
TI  - Pathology of diseases that cause upper gastrointestinal tract bleeding.
AB  - Acute and chronic bleeding from the upper gastrointestinal tract is a common
      indication for endoscopy and hospitalization and is associated with significant
      morbidity and mortality. The causes of upper gastrointestinal bleeding are
      numerous and can result in both acute and chronic hemorrhage. The aim of this
      article is to examine the pathologic features of various diseases associated with
      upper gastrointestinal tract bleeding.

PMID- 21944413
TI  - Epidemiology and role of nonsteroidal antiinflammatory drugs in causing
      gastrointestinal bleeding.
AB  - This article outlines the epidemiology and role of nonsteroidal antiinflammatory
      drugs (NSAIDs) in causing gastrointestinal (GI) bleeding. The morbidity and
      mortality associated with NSAID-induced GI bleeding are discussed, and the
      mechanisms of NSAID-related GI injury, the potency of various NSAIDs, new NSAIDs
      associated with a decrease in GI pathology, dual-acting antiinflammatory drugs,
      hydrogen sulfide-releasing NSAIDs, lipoxygenase/cyclooxygenase, phospholipid
      NSAIDs, and the comprehensive effects of NSAIDs on the GI tract are described.

PMID- 21944414
TI  - The prevalence and incidence of Helicobacter pylori-associated peptic ulcer
      disease and upper gastrointestinal bleeding throughout the world.
AB  - Due to heightened awareness regarding testing for and eradication of infection,
      the prevalence and incidence of H pylori infection (and by extension the
      prevalence and incidence of peptic ulcer disease) appear to have declined in
      recent years. However, antimicrobial resistance is mounting and traditional
      clarithromycin- or metronidazole-containing triple therapies may no longer be
      highly effective at eradicating the infection. Combined bismuth- and
      metronidazole-containing quadruple therapy or sequential 4-drug therapy may be
      better choices for first-line treatment against this unique pathogen that is
      ideally suited to survive in the human stomach.

PMID- 21944415
TI  - The interaction between proton pump inhibitors and clopidogrel and upper
      gastrointestinal bleeding.
AB  - There is increasing concern regarding a possible adverse interaction between
      proton pump inhibitors (PPIs) and clopidogrel that could lead to reduced
      cardiovascular protection by clopidogrel. We performed a literature search for
      relevant original studies and systematic reviews. PPIs likely affect the
      antiplatelet activity of clopidogrel as measured in vitro, and this may be a
      class effect. We conclude that the pharmacodynamic effect has not been translated
      into any clinically meaningful adverse effect. PPI cotherapy reduces the
      incidence of recurrent peptic ulcer and of upper gastrointestinal bleeding among
      patients on clopidogrel.

PMID- 21944416
TI  - The overall approach to the management of upper gastrointestinal bleeding.
AB  - This article presents a practical overview of the approach to managing a patient
      presenting with nonvariceal upper gastrointestinal bleeding (NVUGIB). The authors
      focus on initial resuscitation and risk stratification strategies that should be
      used in the Emergency Department, and put into context the subsequent optimal use
      of pharmacologic and endoscopic therapies and postendoscopic management. It is
      hoped that this framework will provide the reader with a practical and evidence
      based approach to the management of NVUGIB from the patient's initial
      presentation through to hospital discharge.

PMID- 21944417
TI  - Pharmacologic therapy for nonvariceal upper gastrointestinal bleeding.
AB  - There are many clinical outcome measures for evaluation of the effectiveness of a
      pharmacologic agent in the management of upper gastrointestinal bleeding (UGIB).
      As a preemptive treatment, it should reduce the need for emergency endoscopy and
      endoscopic intervention, facilitate the efficient identification of the bleeding
      source and, hence, shorten procedure time and reduce the risk of procedure
      related complications. As an effective adjunctive therapy after endoscopic
      hemostasis, it should reduce the incidence of recurrent bleeding and the need to
      repeat endoscopic hemostasis. This article provides an overview of different
      pharmacologic agents that have been used in the management of UGIB.

PMID- 21944418
TI  - Endoscopic therapy for severe ulcer bleeding.
AB  - Upper gastrointestinal (UGI) bleeding secondary to ulcer disease occurs commonly
      and results in significant patient morbidity and medical expense. After initial
      resuscitation, carefully performed endoscopy provides an accurate diagnosis of
      the source of the UGI hemorrhage and can reliably identify those high-risk
      subgroups that may benefit most from endoscopic hemostasis. Effective endoscopic
      hemostasis of ulcer bleeding can significantly improve outcomes by reducing
      rebleeding, transfusion requirement, and need for surgery, as well as reduce the
      cost of medical care. This article discusses the important aspects of the
      diagnosis and treatment of bleeding from ulcers, with a focus on endoscopic
      therapy.

PMID- 21944420
TI  - New diagnostic imaging technologies in nonvariceal upper gastrointestinal
      bleeding.
AB  - This article covers new endoscopic imaging modalities in nonvariceal upper
      gastrointestinal bleeding, such as Doppler ultrasound probe technology,
      endoscopic ultrasonography, color Doppler optical coherence tomography, and
      magnification endoscopy. A more in-depth discussion of these modalities and the
      published evidence supporting their use are included. Furthermore, the shift in
      focus from identification of conventional visual surface stigmata of recent
      hemorrhage to an assessment and understanding of subsurface blood flow as it
      relates to the bleeding lesion is discussed.

PMID- 21944419
TI  - Radiologic techniques and effectiveness of angiography to diagnose and treat
      acute upper gastrointestinal bleeding.
AB  - The use of catheter-based techniques to treat upper gastrointestinal hemorrhage
      has evolved considerably over the past few decades. At present, the state-of-the
      art interventional suites provide optimal imaging. Coupled with advanced catheter
      technology, the two may be used to manage and treat the patient with acute upper
      gastrointestinal hemorrhage. This article summarizes these techniques and, when
      possible, compares them with other methods such as surgery and endoscopy. The
      specific role of transcatheter embolotherapy is highlighted, alongside an
      additional discussion on pharmacologic infusion of vasopressin.

PMID- 21944421
TI  - Management of nonvariceal upper gastrointestinal bleeding.
AB  - Early surgical involvement in the management of a patient at high risk for
      recurrent bleeding, despite endoscopic intervention, is often optimal to assure
      continuity of care. Close collaboration of the surgical team with
      gastroenterologic endoscopy teams greatly benefits the patient. A detailed
      description of the location of the bleeding process is of great help for the
      surgeon as surgical decision making will be influenced by the distance from the
      gastroesophageal junction or pylorus, location on the anterior or posterior wall,
      greater or lesser curvature or incisura, and the size of the process.

PMID- 21944422
TI  - Basic requirements of gastroenterologists to treat upper gastrointestinal
      bleeding: competency and sedation issues.
AB  - This article reviews the components of adequate training required for a
      gastroenterologist to treat upper gastrointestinal bleeding (UGIB). The current
      status of endoscopic simulators is critically reviewed to determine whether these
      should be part of the UGIB armamentarium in the training of individuals and
      whether credentialing could be accomplished through this method of instruction.
      Finally, the author discusses the appropriate use of sedation in patients with
      UGIB.

PMID- 21944423
TI  - Future innovative therapies to treat upper gastrointestinal bleeding.
AB  - The age of patients admitted to hospital for gastrointestinal bleeding will
      probably continue to rise, pushing the mortality rate upward, and the use of
      arthritic and blood thinning drugs will increase the incidence of
      gastrointestinal bleeding, especially in elderly patients. A slow decrease may be
      seen in the incidence of Helicobacter-induced ulceration and consequent bleeding
      in the west. New vaccine development has the best chance of reducing upper
      gastrointestinal bleeding worldwide, especially that caused by viral infections.
      Innovations in mechanical and compressive thermal hemostasis offer the best
      prospects for improvement in outcome from flexible therapeutic endoscopy.

PMID- 21944424
TI  - Upper GI bleeding.

PMID- 21944426
TI  - Epstein-Barr virus-associated gastric carcinoma.
AB  - Epstein-Barr virus (EBV) has been accepted as an infective agent causing gastric
      carcinoma (GC). EBV-associated GC, comprising nearly 10% of all cases of GC, is
      the monoclonal growth of EBV-infected epithelial cells, which express only
      several EBV-latent genes (Latency I program). Histopathologically, there are two
      subtypes, lymphoepithelioma-like carcinoma and the ordinary type of GC. Other
      features include the lace pattern of carcinoma cells in the intramucosal stage
      and the dense infiltration of lymphocytes and macrophages at the invasive site of
      the submucosa. The primary molecular abnormality in EBV-associated GC is global
      and non-random CpG island methylation in the promoter region of many cancer
      related genes. Experimental studies have demonstrated that viral latent membrane
      protein 2A (LMP2A) is responsible for the promotion of DNA methylation. LMP2A up
      regulates cellular DNMT1 through the phosphorylation of STAT3, resulting in the
      repression of tumor suppressor genes, such as PTEN, through promoter methylation.
      DNA methylation in EBV-infected stomach cells may be due to overdrive of the
      cellular defense against foreign DNA. Further studies on the mechanisms of
      epigenetic abnormalities will clarify the strategies for prevention and treatment
      of this particular type of GC with EBV infection.

PMID- 21944427
TI  - A case of naturally evolving gout in an elderly man.
AB  - Gout is a common disorder in adults that can lead to severe organ decline,
      disability and impaired quality of life due to the formation of periarticular
      tophi. We report a case of massive tophaceous gout in a 78-year-old man with a 16
      year-long history of untreated disease. The patient gradually became disabled,
      his renal function deteriorated, and he finally died of sepsis. Our case
      demonstrates that chronic gout not only affects the joints, but is also
      associated with organ function decline and can, even nowadays, lead to death.

PMID- 21944428
TI  - Incident preclinical mobility disability (PCMD) increases future risk of new
      difficulty walking and reduction in walking activity.
AB  - PURPOSE: This study examines whether and how report of a change in walking
      behavior, incident PCMD, predicts subsequent reduction in walking activity.
      MATERIALS AND METHODS: Data are from a prospective study of 436 community
      dwelling women age 70-79 years. Outcome measures include subjective and objective
      measures of walking ability at 3 years. PRINCIPAL RESULTS: Incident PCMD is
      associated with the loss of walking abilities at 3-years, regardless of baseline
      physical impairment. Compared to women without, women with incident PCMD at 1.5
      years after baseline were 2.7 (95%CI 1.4-7.2) times more likely to report that
      they no longer walk outdoors at least 8 blocks and 4.9 (1.9-13.1) times more
      likely to report new difficulty walking. Incident PCMD was also associated with
      declines in objective outcomes. Incident PCMD is an independent marker of
      subsequent decreased walking activity. MAJOR CONCLUSIONS: Incident PCMD appears
      to be a target for programs to prevent declines in walking activity in older
      adults.

PMID- 21944429
TI  - Functional outcomes in schizophrenia: understanding the competence-performance
      discrepancy.
AB  - A problem in the study and treatment of functional disability in schizophrenia is
      that factors other than competence (what one can do) can limit real-world
      performance (what one does). We examined predictors of the competence-performance
      discrepancy in both adaptive and interpersonal domains. Patients with
      schizophrenia (N = 96) were evaluated at baseline of a clinical treatment study.
      Discrepancy scores were created by considering each subject's competence relative
      to their real-world performance in interpersonal and adaptive behaviour domains.
      Logistic regression analyses revealed that for the interpersonal competence
      performance discrepancy, living in a group home, better neurocognition, more time
      spent in the hospital since a first episode of psychosis, and a longer first
      hospitalization predicted a greater discrepancy between interpersonal competence
      and performance measures. For adaptive behaviour, shorter time since most recent
      hospitalization, more depressive symptoms, greater number of months of first
      hospitalization, older age at baseline, younger age at first hospitalization, and
      more time spent in the hospital since a first episode of psychosis predicted a
      greater adaptive competence-performance discrepancy. A different pattern of
      demographic and clinical features may limit the extent to which patients are
      deploying interpersonal versus adaptive skills in everyday life.

PMID- 21944431
TI  - Radial scar without associated atypical epithelial proliferation on image-guided
      14-gauge needle core biopsy: analysis of 49 cases from a single-centre and review
      of the literature.
AB  - The purpose of this study was to evaluate the reliability of image-guided 14
      gauge needle core biopsy in the diagnosis of radial scar without associated
      atypical epithelial proliferation, by comparison with definitive histological
      diagnosis on surgical excision. The records of 8792 consecutive image-guided 14
      gauge needle core biopsy of the breast performed from January 1996 to December
      2009 were reviewed. Forty-nine cases of radial scar without associated atypical
      epithelial proliferation were identified and compared with definitive
      histological diagnosis on surgical excision. The definitive histological
      diagnosis on surgical excision confirmed the results of image-guided 14-gauge
      needle core biopsy in 36 of 49 cases (73.5%), in 9 cases (18.3%) radial scar was
      associated with atypical epithelial proliferation, while 4 cases out of 49 cases
      were upgraded to carcinoma (3 cases of ductal carcinoma in situ and one case of
      invasive lobular carcinoma), with an underestimation rate of 8.2%. A diagnosis of
      radial scar without associated atypical epithelial proliferation on image-guided
      14-gauge needle core biopsy does not exclude a malignancy on surgical excision;
      consequently during the multidisciplinary discussion further assessment by
      surgical excision or vacuum-assisted excision, as recently reported, needs to be
      considered to obtain a definitive histological diagnosis.

PMID- 21944430
TI  - Prevalence and psychiatric correlates of pain interference among men and women in
      the general population.
AB  - OBJECTIVE: To examine gender differences in the associations of levels of pain
      interference and psychiatric disorders among a nationally representative sample
      of adult men and women. METHOD: Chi-square tests and multinomial logistic
      regression analyses were performed on data obtained from the National
      Epidemiologic Survey on Alcohol and Related Conditions from 42,750 adult
      respondents (48% men; 52% women), who were categorized according to three levels
      of pain interference (i.e., no or low pain interference [NPI], moderate pain
      interference [MPI], severe pain interference [SPI]). RESULTS: Female respondents
      in comparison to male respondents were more likely to exhibit moderate (p <
      0.001) or severe pain interference (p < 0.001). Levels of pain interference were
      associated with past-year Axis I and lifetime Axis II psychiatric disorders in
      both male and female respondents (p < 0.05), with the largest odds typically
      observed in association with moderate or severe pain interference. A stronger
      relationship between MPI and alcohol abuse or dependence (OR = 1.61, p < 0.05)
      was observed in male participants as compared to female ones, while a stronger
      relationship between SPI and drug abuse or dependence (OR = 0.57, p < 0.05) was
      observed in female respondents as compared to male ones. CONCLUSIONS: Levels of
      pain interference are associated with the prevalence of Axis I and Axis II
      psychiatric disorders in both men and women. Differences in the patterns of co
      occurring substance-related disorders between levels of pain interference in male
      and female respondents indicate the importance of considering gender-related
      factors associated with levels of pain interference in developing improved mental
      health prevention and treatment strategies.

PMID- 21944432
TI  - Locking plate fixation of humeral head fractures with a telescoping screw. A
      comparative biomechanical study versus a standard plate.
AB  - OBJECTIVES: Locking plate fixation of humeral head fractures bares the risk of
      glenohumeral screw penetration. In order to circumvent this problem it is
      recommended to insert shorter locking screws having at least a 6mm distance to
      the humeral head cortex. This in turn may reduce fixation stability and may lead
      to early varus displacement. One second frequent failure mechanism is cranial
      displacement of the greater tubercle. The study evaluates the biomechanical
      properties of a locking plate employing an additional telescoping screw that may
      enhance resistance to varus displacement. Screw in screw fixation of the greater
      tubercle may reduce the rate of cranial displacement. METHODS: In four paired
      fresh-frozen human cadaver humeri (age>70 years) a Neer IV/3 fracture was created
      with a 5mm osteotomy gap simulating metaphyseal comminution. Limbs were randomly
      assigned to receive plate fixation with an additional telescoping screw (Humerus
      Tele Screw: HTS) and on the contralateral limb Philos plate fixation before
      biomechanical evaluation (MTS-Bionix 858.2). Standard locking screws were placed
      in both groups 6mm below the radiological head circumference; the telescoping
      screw was placed in the subchondral layer. The greater tubercle was fixed with an
      additional screw in both techniques, in the HTS group the screw was anchored in
      the sleeve of the telescrew (screw in screw fixation). FINDINGS: Fixation
      stability with a mean stiffness of 300.9+/-28.8 N/mm in the HTS plate group
      proved to be significantly higher than in the Philos plate group (184.2+/-23.4
      N/mm; p=0.006). The HTS plate also resisted higher loads in terms of fixation
      failure with loss of reduction at 290+/-58.6 N in comparison to 205+/-8.6 N for
      the Philos plate (p=0.2). Displacement of the greater tubercle occurred in no
      case of the HTS plate group and in two out of four cases in the Philos plate
      group. INTERPRETATION: The HTS plate provides high fixation stability in an in
      vitro humeral head fracture model and securely prevents displacement of the
      greater tubercle.

PMID- 21944433
TI  - Response to "Double jeopardy revisited" with our own Trauma experience.

PMID- 21944434
TI  - Radial neck fractures in children treated with the centromedullary Metaizeau
      technique.
AB  - BACKGROUND: Radial neck fracture in children is infrequent but when not managed
      accurately can lead to complications. Different methods have been developed for
      the reduction and fixation of this fracture. The purpose of this retrospective
      study is to evaluate our results using the Metaizeau centromedullary technique.
      MATERIALS AND METHOD: Our series comprises 19 children with displaced radial neck
      fractures treated in our institution in the period 2004-2008. One patient was
      excluded because of a very complex fracture dislocation of the elbow (exclusion
      criteria). Two patients refused to participate in the follow-up leaving 16 who
      were treated with this technique. Patients were evaluated clinically and
      radiologically. For the clinical evaluation, we used the Metaizeau's
      classification. The subjective evaluation was done using the DASH score, and the
      Steele's classification was used for the evaluation of the radiological results.
      FINDING/RESULTS: We found good clinical and radiological outcomes. The mean DASH
      score was 3.06. Patients who had undergone open reduction had inferior outcome.
      CONCLUSION: Our results are comparable to other studies. This study confirms the
      Metaizeau technique as an excellent treatment option for displaced paediatric
      radial neck fractures.

PMID- 21944436
TI  - Intermediate- and high-risk prostate cancer: a plea for high-dose, high-precision
      intensity-modulated radiotherapy with a modulated duration of androgen
      deprivation therapy.

PMID- 21944435
TI  - Long-term renal function after urinary diversion by ileal conduit or orthotopic
      ileal bladder substitution.
AB  - BACKGROUND: Data on long-term renal function are scarce for ileal conduit
      diversion (ICD) and even rarer for orthotopic ileal bladder substitution (BS).
      OBJECTIVE: Explore the changes in renal function of patients who lived>=10 yr
      with an ICD or BS and determine the risk factors contributing to renal function
      deterioration. DESIGN, SETTING, AND PARTICIPANTS: Fifty consecutive ICD patients
      and 111 consecutive BS patients who lived >=10 yr after undergoing surgery
      between January 1985 and December 2000 were retrospectively analyzed.
      MEASUREMENTS: The glomerular filtration rate (GFR) was calculated with the
      Modification of Diet in Renal Disease (MDRD) equation before and 10 yr after
      surgery. Decreased renal function was defined as a decrease in GFR>10 ml/min per
      1.73 m2 in 10 yr. RESULTS AND LIMITATIONS: Median GFR values in patients with ICD
      or BS decreased from 65.5 (range: 23-90) to 57 (range: 7-100) ml/min per 1.73 m2
      and from 68 (range: 33-106) to 66 (range: 16-100) ml/min per 1.73 m2,
      respectively. Eighteen ICD patients (36%) and 23 BS patients (21%) had
      deteriorating renal function. Seven of 12 ICD patients with obstruction
      (ureteroileal stricture, stomal stenosis/parastomal hernia) (58%) had renal
      function deterioration, as did 17 of 46 BS patients with obstruction
      (ureteroileal/nipple stricture and/or bladder outlet obstruction) (37%). Logistic
      regression analysis confirmed that obstruction was the leading, and an
      independent, risk factor for renal function deterioration for both ICD patients
      (p=0.045) and BS patients (p=0.002). Patients with diabetes or hypertension were
      significantly more likely to have deterioration of renal function if they had ICD
      (p=0.002 and p=0.05, respectively). The limitation of the study is its
      retrospective nature and its composition that included many patients who did not
      survive 10 yr. CONCLUSIONS: Urinary tract obstruction was the leading cause of
      long-term renal function impairment, regardless of whether the patient had ICD or
      BS. ICD patients with predisposing risk factors, such as diabetes or
      hypertension, were at increased risk for impaired renal function.

PMID- 21944437
TI  - Posttraumatic stress disorder in DSM-5: estimates of prevalence and symptom
      structure in a nonclinical sample of college students.
AB  - We empirically investigated recent proposed changes to the posttraumatic stress
      disorder (PTSD) diagnosis for DSM-5 using a non-clinical sample. A web survey was
      administered to 585 college students using the Stressful Life Events Screening
      Questionnaire to assess for trauma exposure but with additions for the proposed
      traumatic stressor changes in DSM-5 PTSD. For the 216 subjects endorsing previous
      trauma exposure and nominating a worst traumatic event, we administered the
      original PTSD Symptom Scale based on DSM-IV PTSD symptom criteria and an adapted
      version for DSM-5 symptoms, and the Center for Epidemiological Studies-Depression
      Scale. While 67% of participants endorsed at least one traumatic event based on
      DSM-IV PTSD's trauma classification, 59% of participants would meet DSM-5 PTSD's
      proposed trauma classification. Estimates of current PTSD prevalence were .4-1.8%
      points higher for the DSM-5 (vs. the DSM-IV) diagnostic algorithm. The DSM-5
      symptom set fit the data very well based on confirmatory factor analysis, and
      neither symptom set's factors were more correlated with depression.

PMID- 21944438
TI  - Modes of failure in explanted mitroflow pericardial valves.
AB  - BACKGROUND: Bioprosthetic heart valves are a treatment option for patients with
      significant valvular disease. We present the first morphologic analysis of a
      series of explanted Mitroflow pericardial valves (model A12) and discuss their
      modes of failure. METHODS: Between 2001 and 2010, 12 Mitroflow (A12) valves
      (Sorin Group Inc, Vancouver, Canada) were examined, grossly and microscopically,
      for postimplantation changes. Cusp tears and thickening, calcification (at
      radiography), pannus formation, inflammation, and thrombus deposition were noted.
      Microscopically, tissue degeneration including the presence of calcification,
      pannus formation, thrombus, collagen disruption, fluid insudation, inflammatory
      cells, and microorganisms were looked for. Causes for dysfunction were then
      identified. RESULTS: There were 12 patients with a mean age of 73.0 +/- 5.3 years
      at implantation. Duration of implantation ranged from 0.25 to 7 years (mean = 2.9
      +/- 2.5 years). Five valves were explanted for infective endocarditis or
      thrombotic vegetations. Primary structural deterioration was observed in 7 of 12
      (58%) valves; characterized by para-stent post cusp tears (42%) and moderate to
      severe calcification (50%). Most valves showed cusp thickening and collagen
      disruption at the stent post and pannus. CONCLUSIONS: Structural valve
      deterioration was observed in 100% of the Mitroflow pericardial valves that had
      been in place for more than 2 years. The high rate of para-stent post cusp tears,
      calcification, and tissue degeneration suggests a link to the design, likely
      associated with mechanical stress, in addition to abrasion with the cross-sutures
      and Dacron fabric at the stent posts.

PMID- 21944439
TI  - Outcomes of simultaneous liver transplantation and elective cardiac surgical
      procedures.
AB  - BACKGROUND: Many centers are reticent to list patients for liver transplantation
      until coexistent cardiac disease is surgically corrected. Previous studies have
      documented considerable morbidity and mortality in liver failure patients
      undergoing cardiac operations. This study examined whether elective cardiac
      operations at the time of hepatic transplantation would yield enhanced outcomes.
      METHODS: Between July 1999 and June 2010, 10 patients underwent simultaneous
      liver transplantation and elective cardiac operations at a single institution.
      Postoperative outcomes were analyzed using a prospectively maintained database.
      RESULTS: The 10 patients were men (mean age, 59.8 +/- 8.3 years): 7 were in Child
      Pugh class B and 3 were in class C. Mean Model for End-Stage Liver Disease score
      was 17.0 +/- 5.8. Cardiac operations included coronary artery bypass grafting in
      1, aortic valve replacement in 4, coronary artery bypass grafting and aortic
      valve replacement in 3, coronary artery bypass grafting and mitral valve repair
      in 1, and tricuspid valve repair in 1. In-hospital mortality was 20%. Mean
      postoperative length of stay was 23 +/- 8 days. Actuarial survival at 3 years was
      70%. CONCLUSIONS: Survival was modestly improved relative to that observed in
      previous studies of advanced liver failure patients undergoing heart operations
      without concomitant hepatic replacement. Moreover, the medium-term survival
      outcomes approach those documented with liver transplant alone. Further studies
      are warranted with this combined surgical strategy to determine if such an
      approach would be routinely preferable to staged repair of cardiac pathology and
      liver transplant.

PMID- 21944440
TI  - Survival after surgery for pathologic stage IA non-small cell lung cancer
      associated with idiopathic pulmonary fibrosis.
AB  - BACKGROUND: Many problems exist in regard to the treatment of lung cancer
      patients with idiopathic pulmonary fibrosis (IPF), but few reported studies have
      investigated the long-term prognosis after pulmonary resection in such patients.
      The purpose of the present study was to determine the postoperative survival of
      patients with pathologic stage IA non-small cell lung cancer (NSCLC) and IPF.
      METHODS: We retrospectively reviewed 350 patients with pathologic stage IA NSCLC
      who underwent pulmonary resections at our institution between September 1994 and
      December 2007. We analyzed and compared 28 of these patients, who had
      simultaneous lung cancer and IPF, with the remaining 322 lung cancer patients
      without IPF. RESULTS: The 5-year survival rates were 54.2% in pathologic stage IA
      lung cancer patients with IPF and 88.3% in those without IPF (p < 0.0001).
      Univariate analyses showed that age, sex, Brinkman Index, limited resection,
      operation time, adenocarcinoma, and IPF were significant prognostic factors for
      survival (p < 0.10). By multivariate analysis, however, only IPF was a
      significant prognostic factor for survival (p = 0.007). Propensity score-matching
      analysis confirmed that only IPF was significant prognostic factor (p = 0.043).
      CONCLUSIONS: The 5-year survival rate of patients with pathologic stage IA NSCLC
      and IPF is 54.2%. IPF has independent, adverse effects on survival of pathologic
      stage IA NSCLC patients treated with pulmonary resection.

PMID- 21944442
TI  - Academic commitment to maternal, newborn, infant, and child health in circumpolar
      regions: a Canadian imperative.

PMID- 21944441
TI  - Transforming growth factor-alpha enhances stem cell-mediated postischemic
      myocardial protection.
AB  - BACKGROUND: Transforming growth factor-alpha (TGF-alpha) has been shown to
      augment mesenchymal stem cell-mediated cardioprotection during acute ischemia and
      reperfusion in isolated heart models. To determine whether this pretreatment
      strategy would be effective in vivo, we hypothesized that the intramyocardial
      injection of mesenchymal stem cells pretreated with TGF-alpha after coronary
      artery ligation would confer greater preservation of cardiac function, reduction
      in infarct size, and reduction myocardial inflammation. METHODS: Sprague-Dawley
      rats underwent left anterior descending coronary artery ligation. Ischemic border
      zones were injected 30 minutes later with vehicle (n = 11), 1 million mesenchymal
      stem cells (n = 9), or mesenchymal stem cells pretreated with TGF-alpha (250
      ng/mL for 24 hours; n = 10). Cardiac function was assessed by echocardiography at
      7 and 28 days after ligation. Infarct size was measured using
      triphenyltetrazolium chloride. Ischemic border zone cytokine expression was
      measured 30 days after infarction. RESULTS: Myocardial function after ligation
      was greatest in hearts injected with cells pretreated with TGF-alpha in
      association with reduced ventricular remodeling and infarct size compared with
      vehicle-injected hearts. Myocardial interleukin 1beta, interleukin 6, and TNF
      alpha concentrations were lower, and Bcl-2 expression was higher, in hearts
      injected with either cell type. Vascular endothelial growth factor and matrix
      metalloproteinase-2 expression were highest in hearts that received pretreated
      cells. CONCLUSIONS: Intramyocardial injection of mesenchymal stem cells
      pretreated with TGF-alpha further protects cardiac function and reduces infarct
      size compared with injection of untreated cells. Pretreating donor cells with TGF
      alpha may be useful for enhancing cell-based therapies for myocardial ischemia.

PMID- 21944443
TI  - Ministerial message from the Canadian Minister of Health.

PMID- 21944444
TI  - Intra-abdominal hypertension and abdominal compartment syndrome: the journey
      forward.
AB  - Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are
      recognized causes of significant morbidity and mortality among a wide variety of
      critically ill patient populations. Our understanding of IAH and ACS as causes of
      organ failure and patient death has increased  significantly over the past two
      decades since their "rediscovery" as clinically important disease processes. The
      development of consensus definitions and recommendations for the diagnosis and
      management of IAH/ACS, patient care algorithms, an international clinical
      research working  group, and other educational tools have advanced efforts to
      improve patient outcome. Nonoperative management strategies to reduce elevated
      intra-abdominal pressure (IAP) and early surgical intervention for refractory
      IAH/ACS have been demonstrated to significantly improve patient survival.  It is
      only through such a comprehensive, goal-directed approach that patient outcome
      will continue to improve. Despite the significant advances that have been made,
      the journey toward conquering IAH/ACS as a cause of patient death after injury
      and/or illness has only just begun. It is remarkable  to consider that two
      decades ago, IAH, the detrimental physiological effects of elevated IAP and ACS,
      the development of IAH-induced organ dysfunction and failure were essentially
      unrecognized as causes of morbidity and mortality among critically ill adult and
      pediatric patients. It is not  because these disease processes have been recently
      discovered. The pathophysiological impact of elevated IAP on cardiac, pulmonary,
      and renal function was well defined over 150 years ago. It has only been within
      the past 15 years that physicians and nurses worldwide rediscovered this long
      forgotten  pathophysiological knowledge and began to actively reconsider these
      two disease processes in their patient's daily differential diagnosis. Originally
      considered diseases affecting solely the traumatically injured, IAH and ACS are
      now recognized to occur in both medical and surgical patients  of any age and to
      result from a wide range of injuries and disease processes. Tremendous progress
      has been made in recent years with regard to our understanding of the diagnosis
      and management of IAH and ACS. Within this special supplement of The American
      Surgeon, you will find a series  of "state-of-the-art" reviews authored by a
      number of the world's experts on IAH/ACS as well as abstracts of research that
      will be presented at the Fifth World Congress on the Abdominal Compartment
      Syndrome (Lake Buena Vista, Florida, August 10-13, 2011). This commentary  will
      review where we were, where we are today, and where we are going with respect to
      the future of IAH and ACS.

PMID- 21944445
TI  - Definitions and pathophysiological implications of intra-abdominal hypertension
      and abdominal compartment syndrome.
AB  - For any syndrome or disease process, uniform definitions are essential to
      facilitate effective clinical communication as well as evaluation of the
      scientific literature and standardization of research. The following consensus
      definitions for intra-abdominal hypertension (IAH) and abdominal  compartment
      syndrome (ACS) have been proposed by the World Society of the Abdominal
      Compartment Syndrome and are now widely accepted around the world. The use of
      these definitions, and their subsequent revisions as new evidence becomes
      published, will further improve communication and future  research in this area.
      This review briefly addresses the present definitions as well as the
      pathophysiological effects of IAH/ACS on end-organ function.

PMID- 21944446
TI  - Patient populations at risk for intra-abdominal hypertension and abdominal
      compartment syndrome.
AB  - Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are
      critical care conditions with significant morbidity and mortality. The surgical
      measure to treat ACS (decompressive laparotomy) is hazardous and results in an
      open abdomen with potential major complications  such as fistulas, abscesses, and
      large ventral hernias. As a result of the complicated natural history of IAH/ACS
      as well as significant morbidity and mortality, prevention is a logical approach
      to this complex problem. Knowledge of the patient populations at high risk for
      developing IAH/ACS  is crucial. The aim of this review is to discuss the high
      risk populations for acute IAH/ACS among surgical patients.

PMID- 21944447
TI  - Intra-abdominal measurement techniques: is there anything new?
AB  - Intra-abdominal pressure (IAP) measurements are essential to the diagnosis and
      management of intra-abdominal hypertension (IAH) and abdominal compartment
      syndrome. A variety of IAP measurement techniques have been described. The
      intravesicular or "bladder" technique remains  the gold standard. This commentary
      reviews each of the different techniques for IAP measurement and discusses their
      clinical application. It also explores how IAP is affected by changes in body
      position, body mass index, and positive end-expiratory pressure (PEEP). IAP
      should be measured every  4 to 6 hours in patients with risk factors for IAH.
      Putting patients in the semirecumbent position changes the IAP measurement
      significantly. The role of prone positioning in unstable patients with IAH
      remains unclear. PEEP has a small effect on IAP.

PMID- 21944448
TI  - Cardiopulmonary monitoring in intra-abdominal hypertension.
AB  - Cardiopulmonary dysfunction and failure are commonly encountered in the patient
      with intra-abdominal hypertension (IAH) or abdominal compartment syndrome.
      Accurate assessment and optimization of preload, contractility, and afterload in
      conjunction with appropriate goal-directed resuscitation  and assessment of fluid
      responsiveness are essential to restore end-organ perfusion. In patients with
      IAH, the traditional "barometric" preload indicators such as pulmonary artery
      occlusion pressure and central venous pressure are erroneously increased.
      Volumetric monitoring techniques  have been proven to be superior in directing
      the appropriate resuscitation together with targeted abdominal perfusion
      pressure. If such limitations are not recognized, misinterpretation of the
      patient's cardiac status is likely, resulting in inappropriate and potentially
      detrimental therapy.  IAH also markedly affects the mechanical properties of the
      chest wall and consequently also the respiratory function. Altered mechanical
      properties of the chest wall may limit ventilation, influence the work of
      breathing, affect the interaction between the respiratory muscles, hasten the
      development  of respiratory failure, and interfere with gas exchange. Pulmonary
      monitoring is important to understand the relationships between intra-abdominal
      pressure and chest wall mechanics and the impact of IAH on ventilator-induced
      lung injury, lung distention, recruitment, and lung edema.

PMID- 21944449
TI  - Resuscitation in intra-abdominal hypertension and abdominal compartment syndrome.
AB  - Resuscitation and the development of abdominal compartment syndrome (ACS) are
      closely associated and frequently overlapping critical care topics. Elevated
      intra-abdominal pressure (IAP) can cause major deterioration of cardiac function
      by affecting preload, contractility, and afterload.  Pathologically elevated IAPs
      are often compounded by the presence of shock leading to imminent organ failure.
      Excessive or overzealous resuscitation in an attempt to restore perfusion and
      correct these organ dysfunctions and failures can worsen elevated IAP and
      increase the risk of ACS. The  aim of this review is to discuss these multilevel
      interactions between resuscitation and ACS identifying appropriate resuscitative
      strategies for the patient with elevated IAP.

PMID- 21944450
TI  - Nonoperative management of intra-abdominal hypertension and abdominal compartment
      syndrome: evolving concepts.
AB  - Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are
      associated with significant morbidity and mortality. Nonoperative medical
      management strategies play an important role in the current treatment of IAH and
      ACS. There are five medical treatment options to  be considered to reduce
      elevated intra-abdominal pressure (IAP): 1) improvement of abdominal wall
      compliance; 2) evacuation of intraluminal contents; 3) evacuation of abdominal
      fluid collections; 4) optimization of systemic and regional perfusion; and 5)
      correction of positive fluid balance.  Nonsurgical management is an important
      treatment option in critically ill patients with raised IAP.

PMID- 21944451
TI  - Surgical management of intra-abdominal hypertension and abdominal compartment
      syndrome.
AB  - The initial management of intra-abdominal hypertension (IAH) is medical measures
      to reduce intra-abdominal pressure (IAP). These, in combination with percutaneous
      drainage of peritoneal free fluid, may serve to reduce IAH. If these measures
      fail, surgical decompression of the abdomen  by laparotomy is necessary to
      control the IAP, search for and treat inciting factors, and reduce the
      hypertension. The abdomen is usually left open with temporary abdominal closure
      techniques. Surgical decompression of IAH associated with acute pancreatitis or
      secondary abdominal compartment  syndrome has other surgical options besides a
      complete celiotomy. Attention to detail in surgical technique and postoperative
      care is essential for optimal outcome.

PMID- 21944452
TI  - Temporary abdominal closure techniques.
AB  - Open abdomen treatment (OAT) is increasingly used, most often to prevent intra
      abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) after
      emergency abdominal surgery. The goal of temporary abdominal closure (TAC)
      techniques no longer is abdominal coverage alone, but  fluid control and
      facilitation of early fascial closure are now important aspects. Various methods
      are available, but negative pressure therapy seems to be best suited to achieve
      these goals. Fascial approximation techniques prevent lateral retraction of the
      abdominal muscles and can be combined  with TAC techniques. Mesh-mediated vacuum
      assisted wound closure is emerging as one of the most promising approaches for
      OAT. In the intensive care unit, continued attention to IAH/ACS and measures to
      prevent or treat these conditions is imperative.

PMID- 21944453
TI  - Alternatives to formal abdominal decompression.
AB  - Open abdominal decompression (OAD) is a potentially life-saving but arguably
      invasive treatment for intra-abdominal hypertension (IAH) and/or abdominal
      compartment syndrome (ACS). Although OAD has previously been considered the only
      therapeutic option for IAH/ACS, the application of  comprehensive nonoperative
      medical management strategies to reduce elevated intra-abdominal pressure and
      restore organ perfusion has recently been shown to decrease progression to ACS
      and the need for OAD. Furthermore, a variety of minimally invasive therapies have
      been developed for the treatment  of patients who would traditionally have
      required OAD. In general, these therapies are most applicable for patients with
      secondary rather than primary IAH leading to ACS.

PMID- 21944454
TI  - Closure of the open abdomen.
AB  - The open abdomen is a valuable tool in the management of patients with intra
      abdominal hypertension and abdominal compartment syndrome. The longer an abdomen
      is left open, the greater the potential morbidity, however. From the very start,
      specific measures should be considered to increase  the likelihood of definitive
      closure and prevent the development of visceral adhesions, lateralization, and/or
      loss of skin and fascia, ileus, fistulae, and malnutrition. Early definitive
      closure of all abdominal wall layers is the short-term goal of management once
      the need for the open abdomen  has resolved. Several devices and strategies
      improve the chances for definitive closure. If a frozen abdomen develops, split
      thickness skin grafting of a granulating open abdominal wound base is an
      alternative. Early coverage of the exposed viscera and acceptance of a large
      abdominal hernia  permit earlier reversal of the catabolic state and lower the
      risk of fistula formation. When a stoma is required, sealing and separation can
      become problematic. If a fistula develops, a more complex situation prevails,
      requiring specific techniques to isolate its output and a longer-term strategy 
      to restore intestinal continuity. Planning the closure of an open abdomen is a
      process that starts on the first day that the abdomen is opened. Multiple factors
      need to be addressed, optimized, and controlled to achieve the best outcome.

PMID- 21944455
TI  - Intra-abdominal hypertension and abdominal compartment syndrome in nontrauma
      surgical patients.
AB  - Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are
      commonly encountered in nontrauma surgical patients. Depending on the etiology of
      the patient's surgical illness (ruptured abdominal aortic aneurysm, acute
      pancreatitis, burns, etc.), both the incidence  and mortality of IAH/ACS may be
      quite high. Recent advances in both the diagnosis and resuscitation of these
      surgical patients have resulted in significantly improved survival over that seen
      in years past. Intra-abdominal pressure measurements should be performed in any
      surgical patient who  demonstrates risk factors for IAH/ACS.

PMID- 21944456
TI  - Intra-abdominal hypertension and abdominal compartment syndrome in the medical
      patient.
AB  - Critically ill medical patients are at significant risk for developing intra
      abdominal hypertension (IAH) and abdominal compartment syndrome (ACS). Although
      surgical IAH/ACS is commonly acute and dramatic in onset, medical IAH/ACS is more
      slow and insidious in its development but no  less deadly. The presence of pre
      existing comorbid illnesses among medical patients imparts morbidity and
      mortality rates that are significantly greater than those of their surgical
      counterparts. A variety of effective medical management strategies for reducing
      elevated intra-abdominal pressure  (IAP), coupled with early abdominal
      decompression when necessary, has been demonstrated to significantly improve
      patient survival from IAH/ACS. Serial IAP measurements, increased collaboration
      between surgeon and nonsurgeon, institution of medical management strategies, and
      early abdominal  decompression for refractory IAH/ACS will lead to decreased
      rates of organ failure and improved survival for medical patients who develop
      IAH/ACS.

PMID- 21944457
TI  - Abdominal compartment syndrome: focus on the children.
AB  - This article is a concise summary of intra-abdominal hypertension (IAH) and
      abdominal compartment syndrome (ACS) with an emphasis on factors relevant to
      their occurrence in children. It discusses the limitations in the direct
      application of the current World Society of Abdominal Compartment  Syndrome
      consensus definitions and extrapolation of management practices derived from
      studying adult patients to the pediatric age group. Techniques that may be used
      for measuring intra-abdominal pressure (IAP) in children, normal IAP ranges, risk
      factors for developing ACS as well as current  medical and surgical management
      options in children are discussed.

PMID- 21944458
TI  - Long-term implications of intra-abdominal hypertension and abdominal compartment
      syndrome: physical, mental, and financial.
AB  - Patient survival after the development of intra-abdominal hypertension (IAH) and
      abdominal compartment syndrome (ACS) has improved significantly over the past two
      decades through improved diagnosis and multidisciplinary management. Published
      mortality rates approaching 100 per cent  have been replaced by mortality rates
      of 20 to 50 per cent depending on age and mechanism of injury. Simultaneously,
      same-admission definitive abdominal closure rates of almost 90 per cent have been
      reported by several centers. The seemingly aggressive management techniques
      required to achieve  this success have been shown to be associated with excellent
      long-term physical and mental health outcome. Appropriate management of the
      patient with IAH/ACS is associated with both significantly improved patient
      survival and decreased resource use. These improvements are easily achievable  by
      virtually any hospital through adoption of a multidisciplinary IAH/ACS management
      protocol.

PMID- 21944459
TI  - Normal hepatocyte transplantation delays the emergence of chemically induced
      preneoplastic nodules in rat liver.
AB  - Cancer often arises in a background of chronic tissue damage. It is also
      increasingly appreciated that such an injured tissue microenvironment might
      foster the selective emergence of altered cells, leading to neoplasia.
      Accordingly, reversal of chronic tissue damage could represent  a potential
      strategy to counteract neoplastic disease. In these studies, we aim to
      investigate whether transplantation of normal cells in the context of an injured,
      neoplastic-prone microenvironment might impact on the evolution of the
      carcinogenic process. A rat model of chemically induced  hepatocarcinogenesis was
      used. Animals were given a single dose of diethylnitrosamine (DENA), followed by
      two injections of retrorsine (RS), a pyrrolizidine alkaloid that imposes a
      persistent block on hepatocyte cell cycle. At the end of this protocol, rats were
      either given no further treatment  or injected, via the portal circulation, with
      4 million normal hepatocytes isolated from a syngenic donor. After 3 months, rats
      given DENA+RS alone displayed numerous discrete nodular lesions (up to 30 per
      liver), ranging 1 to 3 mm in size. On the other hand, in animals receiving
      DENA+RS and  transplantation, donor hepatocytes were able to repopulate over 50%
      of the host liver, as expected. Most importantly, both the number and the size of
      hepatocyte nodules were greatly reduced in these animals (percent nodular area
      was 1.8 +/- 0.3, down from a control value of 8.5 +/-  2.8). The above data
      indicate that strategies aimed at reestablishing a normal tissue microenvironment
      might be relevant to the management of neoplastic disease.

PMID- 21944460
TI  - Nutrition in phenylketonuria.
AB  - The same basic principles are used to deliver dietary treatment in PKU that was
      developed sixty years ago. Dietary treatment is undoubtedly very successful, but
      it has gradually evolved and been guided commonly by individual experience and
      expert opinion only. There is little international consensus about dietary
      practice with improvements in specialist dietary products concentrating on taste
      and presentation rather than nutritional composition. Many areas of dietary
      treatment have not been rigorously examined. In particular, the amino acid and
      micronutrient profile of Phenylalanine-free (phe-free) amino acids requires
      further study. In different formulations of phe-free amino acids, there are
      variations in the amino acid patterns as well the amount of essential and non
      essential amino acids per 100g/amino acids. The amount of added tyrosine and
      branch chain amino varies substantially, and in PKU specifically, there is little
      data about their relative absorption rates and bioavailability. In phe-free amino
      acids, there is evidence suggesting that some of the added micronutrients may be
      excessive and so the source and amount of each micronutrient should be
      scrutinized, with a need for the development of international nutritional
      composition standards exclusively for these products. There is a dearth of data
      about the life-long phenylalanine tolerance of patients or the nutritional state
      of adult patients treated with diet. There is a growing need to measure body
      composition routinely in children with PKU and with the rise in childhood
      obesity, it is important to measure body fatness and identify those who are at
      greatest risk of 'co-morbidities' of obesity. There is necessity for
      international collaboration to ensure robust data is collected on many basic
      aspects of nutritional care to guarantee that diet therapy is delivered to the
      highest standard.

PMID- 21944461
TI  - The unsolved puzzle of neuropathogenesis in glutaric aciduria type I.
AB  - Glutaric aciduria type I (GA-I) is a cerebral organic aciduria caused by
      deficiency of glutaryl-Co-A dehydrogenase (GCDH). GCDH deficiency leads to
      accumulation of glutaric acid (GA) and 3-hydroxyglutaric acid (3-OHGA), two
      metabolites that are believed to be neurotoxic, in brain and body fluids. The
      disorder usually becomes clinically manifest during a catabolic state (e.g.
      intercurrent illness) with an acute encephalopathic crisis that results in
      striatal necrosis and in a permanent dystonic-dyskinetic movement disorder. The
      results of numerous in vitro and in vivo studies have pointed to three main
      mechanisms involved in the metabolite-mediated neuronal damage: excitotoxicity,
      impairment of energy metabolism and oxidative stress. There is evidence that
      during a metabolic crisis GA and its metabolites are produced endogenously in the
      CNS and accumulate because of limiting transport mechanisms across the blood
      brain barrier. Despite extensive experimental work, the relative contribution of
      the proposed pathogenic mechanisms remains unclear and specific therapeutic
      approaches have yet to be developed. Here, we review the experimental evidence
      and try to delineate possible pathogenetic models and approaches for future
      studies.

PMID- 21944462
TI  - 5-aminoimidazole-4-carboxamide riboside enhances effect of ionizing radiation in
      PC3 prostate cancer cells.
AB  - PURPOSE: The nucleoside 5-aminoimidazole-4-carboxamide riboside (AICAR) is a low
      energy mimetic and adenosine monophosphate (AMP)-activated protein kinase (AMPK)
      agonist that can affect the phenotype of malignant cells by diminishing their
      anabolism. It does this by being converted to 5-aminoimidazole-4-carboxamide
      ribotide (ZMP), an AMP analog. We combined this promising antineoplastic agent
      with ionizing radiation in an attempt to increase its efficacy. METHODS AND
      MATERIALS: The effect of AICAR on cell proliferation, cell viability, apoptosis,
      reactive oxygen species production, radiosensitivity, and AMPK activation was
      determined in the human prostate cancer cell line PC3. To elucidate the
      radiosensitizing mechanism, clonogenic survival assays in the presence of a drug
      agonist or antagonist or with small interfering RNA targeting AMPK were done, as
      well as measurements of ZMP production and double strand break repair. Moreover,
      immunoblot analysis of the radiation response signaling pathways after AICAR
      treatment was performed. RESULTS: The incubation of human PC3 prostate cancer
      cells with AICAR-activated AMPK inhibited cell proliferation, decreased
      viability, increased apoptosis, and generated reactive oxygen species in a dose-
      and time-dependent manner. None of these endpoints gave more than additive
      effects when radiation was added. Radiosensitization was observed but only after
      72 hours of treatment with 250 MUM AICAR, suggesting that it was independent of
      AMPK activation. This finding was confirmed by small interfering RNA knockdown of
      AMPK. The mechanism of radiosensitization was associated with imbalanced
      deoxynucleotide pools owing to ZMP accumulation after AICAR administration that
      interfered with DNA repair. CONCLUSIONS: Our findings on the favorable
      interaction between low doses of AICAR and ionizing radiation in PC3 cells could
      open new perspectives for the clinical use of this or similar compounds. However,
      additional research is still required to establish the ZMP pathway as being of
      general applicability.

PMID- 21944463
TI  - Type of diabetes mellitus and the odds of Gleason score 8 to 10 prostate cancer.
AB  - PURPOSE: It has been recently shown that diabetes mellitus (DM) is significantly
      associated with the likelihood of presenting with high-grade prostate cancer
      (PCa) or Gleason score (GS) 8 to 10; however, whether this association holds for
      both Type 1 and 2 DM is unknown. In this study we evaluated whether DM Type 1, 2,
      or both are associated with high-grade PCa after adjusting for known predictors
      of high-grade disease. METHODS AND MATERIALS: Between 1991 and 2010, a total of
      15,330 men diagnosed with PCa and treated with radiation therapy were analyzed. A
      polychotomous logistic regression analysis was performed to evaluate whether Type
      1 or 2 DM was associated with odds of GS 7 or GS 8 to 10 compared with 6 or lower
      PCa, adjusting for African American race, age, prostate-specific antigen (PSA)
      level, and digital rectal examination findings. RESULTS: Men with Type 1 DM
      (adjusted odds ratio [AOR], 2.05; 95% confidence interval [CI], 1.28-3.27; p =
      0.003) or Type 2 DM (AOR, 1.58; 95% CI, 1.26-1.99; p < 0.001) were significantly
      more likely to be diagnosed with GS 8 to 10 PCa compared with nondiabetic men.
      However this was not true for GS 7, for which these respective results were AOR,
      1.30; 95% CI, 0.93-1.82; p = 0.12 and AOR, 1.13; 95% CI, 0.98-1.32; p = 0.10.
      CONCLUSION: Type 1 and 2 DM were associated with a higher odds of being diagnosed
      with Gleason score 8 to 10 but not 7 PCa. Pending validation, men who are
      diagnosed with Type I DM with GS 7 or lower should be considered for additional
      workup to rule out occult high-grade disease.

PMID- 21944464
TI  - Impact of lymph node status on clinical outcomes after accelerated partial breast
      irradiation.
AB  - PURPOSE: To compare outcomes after accelerated partial breast irradiation (APBI)
      between node-negative and node-positive patients. METHODS AND MATERIALS: A total
      of 534 patients with early-stage breast cancer received APBI including 39 node
      positive (N+) cases. Clinical, pathologic, and treatment-related factors were
      compared between node-negative (N-) and N+ cohorts. Local recurrence (LR),
      regional recurrence (RR), axillary failure (AF), distant metastases (DM), disease
      free survival (DFS), cause-specific survival (CSS), and overall survival (OS)
      were analyzed. RESULTS: N+ patients were younger (p = 0.04), had larger tumors (p
      < 0.001), and were more likely to receive chemotherapy (p < 0.001). Mean follow
      up was 7.8 years for N+ patients and 6.3 years for N- patients (p = 0.06). No
      differences were seen in 5-year actuarial rates of LR (2.2% vs. 2.6%, p = 0.86),
      AF (0% vs. 0%, p = 0.69), DFS (90.0% vs. 88.0%, p = 0.79), or OS (91.0 vs. 84.0%,
      p = 0.65) between the two groups, whereas higher rates of RR (0% vs. 6.1%, p <
      0.001) and DM (2.2% vs. 8.9%, p = 0.005) were noted in N+ patients. A trend for
      improved CSS (p = 0.06), was seen in N- patients. Age, tumor size, receptor
      status, T-stage, chemotherapy, APBI technique, and nodal status (p = 0.86) were
      not associated with LR, while a trend for an association with LR was noted with
      close/positive margins, (p = 0.07), and failure to receive adjuvant hormonal
      therapy (p = 0.06). CONCLUSIONS: No differences were seen in the rates of LR or
      AF between N- and N+ patients after APBI. These results support the continued
      enrollment of node-positive patients in Phase III trials evaluating the efficacy
      of APBI including the National Surgical Adjuvant Breast and Bowel Project
      B39/Radiation Therapy Oncology Group 0413.

PMID- 21944465
TI  - Natural antibodies related to metabolic and mammary health in dairy cows.
AB  - Natural antibodies (NAb) are defined as antibodies that circulate in normal
      healthy individuals under the absence of deliberate antigenic stimulation. Two
      types of NAb are distinguished: NAb towards exogenous antigens and NAb towards
      autoantigens (N(A)Ab). The objectives of the current study were threefold. First,
      we studied the relation between metabolic health and concentrations of NAb
      binding keyhole limpet hemocyanin (KLH) or lipopolysaccharide (LPS) in milk and
      plasma of dairy cows in early lactation. Second, we determined the presence of
      N(A)Ab binding transferrin, myosin and thyroglobulin in bovine milk. Third, we
      studied the relation between N(A)Ab in bovine milk and mammary health. For the
      first objective, dairy cows were either fed a control (C) (n=8) or a diet where 2
      kg of concentrates were replaced by an iso-energetic concentrate containing
      marine algae (ALG) from week -3 till 8 postpartum (experiment 1). Plasma and milk
      samples were analyzed weekly for NAb binding either KLH or LPS. Plasma was
      analyzed for glucose, non-esterified fatty acids (NEFA) and beta-hydroxybutyrate
      (BHBA). For the second and third objective, milk samples were collected weekly
      from 96 dairy cows from week 2 till 9 postpartum and analyzed for milk
      composition and N(A)Ab binding myosin, transferrin and thyroglobulin (experiment
      2). For both datasets, N(A)Ab titers are expressed as (2)log values of the
      highest dilution giving a positive reaction. Data are expressed as means +/- SEM.
      Repeated observations were analyzed in a mixed model. In experiment 1, no diet
      effect (P>0.05) was observed on NAb binding LPS in plasma or milk, NAb binding
      KLH in milk was greater (P=0.05) for cows fed the control diet. Concentration of
      NAb binding KLH and LPS in plasma was negatively related to plasma NEFA
      concentration (P<0.05). In experiment 2, NAb binding myosin (5.66 +/- 0.06),
      thyroglobulin (4.85 +/- 0.06), and transferrin (5.76 +/- 0.07) were identified in
      milk. Clinical mastitis incidence (9%) tended to be positively related to
      concentration of NAb binding myosin (P=0.06) and negatively related to Nab
      binding transferrin (P=0.08). In conclusion, NAb binding KLH and LPS in plasma
      and milk are related to metabolic health, as indicated by plasma NEFA
      concentration. Furthermore, this study demonstrates the presence of N(A)Ab in
      bovine milk and shows trends for a relation between N(A)Ab binding auto-antigens
      and mastitis. Future studies should confirm these trends and shed light on the
      predictive value of N(A)Ab in bovine milk for mammary health.

PMID- 21944466
TI  - Risk factors for displaced abomasum or ketosis in Swedish dairy herds.
AB  - Risk factors associated with high or low long-term incidence of displaced
      abomasum (DA) or clinical ketosis were studied in 60 Swedish dairy herds, using
      multivariable logistic regression modelling. Forty high-incidence herds were
      included as cases and 20 low-incidence herds as controls. Incidence rates were
      calculated based on veterinary records of clinical diagnoses. During the 3-year
      period preceding the herd classification, herds with a high incidence had a
      disease incidence of DA or clinical ketosis above the 3rd quartile in a national
      database for disease recordings. Control herds had no cows with DA or clinical
      ketosis. All herds were visited during the housing period and herdsmen were
      interviewed about management routines, housing, feeding, milk yield, and herd
      health. Target groups were heifers in late gestation, dry cows, and cows in early
      lactation. Univariable logistic regression was used to screen for factors
      associated with being a high-incidence herd. A multivariable logistic regression
      model was built using stepwise regression. A higher maximum daily milk yield in
      multiparous cows and a large herd size (p=0.054 and p=0.066, respectively) tended
      to be associated with being a high-incidence herd. Not cleaning the heifer
      feeding platform daily increased the odds of having a high-incidence herd
      twelvefold (p<0.01). Keeping cows in only one group in the dry period increased
      the odds of having a high incidence herd eightfold (p=0.03). Herd size was
      confounded with housing system. Housing system was therefore added to the final
      logistic regression model. In conclusion, a large herd size, a high maximum daily
      milk yield, keeping dry cows in one group, and not cleaning the feeding platform
      daily appear to be important risk factors for a high incidence of DA or clinical
      ketosis in Swedish dairy herds. These results confirm the importance of housing,
      management and feeding in the prevention of metabolic disorders in dairy cows
      around parturition and in early lactation.

PMID- 21944467
TI  - Low pulmonary vascular compliance predisposes post-Fontan patients to protein
      losing enteropathy.
AB  - BACKGROUND: Protein-losing enteropathy (PLE) is a life-threatening and poorly
      understood complication after the Fontan operation. We sought to determine the
      pre-operative risk factors for PLE which developed after the extracardiac conduit
      Fontan operation. METHODS: Two hundred thirty-five patients who underwent the
      extracardiac conduit Fontan operation as an initial Fontan type procedure (median
      age at operation: 3.5 years) were enrolled in this cross-sectional retrospective
      study. Pre-operative and peri-operative variables were surveyed through a review
      of medical records. RESULTS: Within the median follow-up duration of 5 years, 12
      patients developed PLE (12/234, 5.1%) at a median interval of 2.2 years after the
      Fontan procedure, and 4 died of PLE at a median interval of 1.2 years (range 0.21
      7.62) after diagnosis. Factors found to be related to the time to the development
      of PLE on univariate analysis were pulmonary vascular compliance (Cpv)
      (p=0.0019), central venous pressure at postoperative 12 hours (p=0.0026), days of
      ICU stay (P=0.0449), days of hospitalization (p=0.0135), and days of chest tube
      indwelling (p=0.0493). Multivariate analysis, however, showed that only Cpv
      (p=0.0367) remained significant. The range of Cpv was 8.8-26.1 mm(2)/m(2)/mmHg
      (median 17.9) in patients with PLE, and 6.6-122.3 mm(2)/m(2)/mmHg (median 26.8)
      in patients without PLE. CONCLUSIONS: Low pulmonary vascular compliance is
      associated with the development of PLE after the extracardiac conduit Fontan
      operation.

PMID- 21944468
TI  - The effect of detergent-based decellularization procedures on cellular proteins
      and immunogenicity in equine carotid artery grafts.
AB  - Decellularized equine carotid arteries (dEAC) may represent a reasonable
      alternative to alloplastic materials in vascular replacement therapy.
      Acellularity of the matrix is standardly evaluated by DNA quantification what
      however may not record sufficiently the degree of matrix immunogenicity. Thus,
      our aim was to analyze dEAC with a low DNA content for residual cellular
      proteins. A detergent-based decellularization protocol including endonuclease
      treatment resulted in dEAC with 0.6 +/- 0.15 ng DNA/mg dry weight representing
      0.33 +/- 0.14% of native tissue DNA content. In contrast, when matrices were
      homogenized and extracted by high detergent concentrations westernblot analyses
      revealed cytosolic and cytosceleton proteins like GAPDH and smooth muscle actin
      which were depleted to 4.1 +/- 1.9% and 13.8 +/- 0.55%, resp. Also putative
      immunogenic MHC I complexes and the alpha-Gal epitop were reduced to only 14.8 +/
      1.2% and 15.1 +/- 2.05%. Mass spectrometry of matrix extracts identified 306
      proteins belonging to cytosol, organelles, nucleus and cell membrane. Moreover,
      aqueous matrix extracts evoked a pronounced antibody formation when administered
      in mice and thus display high immunogenic potential. Our data indicate that an
      established decellularization protocol which results in acellular matrices
      evaluated by low DNA content reduces but not eliminates cellular components which
      may contribute to its immunogenic potential in vivo.

PMID- 21944469
TI  - The significance of plasmid DNA preparations contaminated with bacterial genomic
      DNA on inflammatory responses following delivery of lipoplexes to the murine
      lung.
AB  - Non-viral gene transfer using plasmid DNA (pDNA) is generally acknowledged as
      safe and non-immunogenic compared with the use of viral vectors. However, pre
      clinical and clinical studies have shown that non-viral (lipoplex) gene transfer
      to the lung can provoke a mild, acute inflammatory response, which is thought to
      be, partly, due to unmethylated CG dinucleotides (CpGs) present in the pDNA
      sequence. Using a murine model of lung gene transfer, bronchoalveolar lavage
      fluid was collected following plasmid delivery and a range of inflammatory
      markers was analysed. The results showed that a Th1-related inflammatory cytokine
      response was present that was substantially reduced, though not abolished, by
      using CpG-free pDNA. The remaining minor level of inflammation was dependent on
      the quality of the pDNA preparation, specifically the quantity of contaminating
      bacterial genomic DNA, also a source of CpGs. Successful modification of a
      scalable plasmid manufacturing process, suitable for the production of clinical
      grade pDNA, produced highly pure plasmid preparations with reduced genomic DNA
      contamination. These studies help define the acceptable limit of genomic DNA
      contamination that will impact FDA/EMEA regulatory guidelines defining clinical
      grade purity of plasmid DNA for human use in gene therapy and vaccination
      studies.

PMID- 21944470
TI  - Molecular imaging of a cancer-targeting theragnostics probe using a nucleolin
      aptamer- and microRNA-221 molecular beacon-conjugated nanoparticle.
AB  - MicroRNAs (miRNA, miR) have been reported as cancer biomarkers that regulate
      tumor suppressor genes. Hence, simultaneous detecting and inhibiting of miRNA
      function will be useful as a cancer theragnostics probe to minimize side effects
      and invasiveness. In this study, we developed a cancer-targeting therangostics
      probe in a single system using an AS1411 aptamer - and miRNA-221 molecular beacon
      (miR-221 MB)-conjugated magnetic fluorescence (MF) nanoparticle (MFAS miR-221 MB)
      to simultaneously target to cancer tissue, image intracellularly expressed miRNA
      221 and treat miRNA-221-involved carcinogenesis. AS1411 aptamer-conjugated MF
      (MFAS) nanoparticles displayed a great selectivity and delivery into various
      cancer cell lines. The miR-221 MB detached from the MFAS miR-221 MB in the
      cytoplasm of C6 cells clearly imaged miRNA-221 biogenesis and simultaneously
      resulted in antitumor therapeutic effects by inhibiting miRNA function,
      indicating a successful astrocytoma-targeting theragnostics. MFAS miRNA MB can be
      easily applied to other cancers by simply changing a targeted miRNA highly
      expressed in cancers.

PMID- 21944472
TI  - Mating disruption by a synthetic sex pheromone in the white grub beetle
      Dasylepida ishigakiensis (Coleoptera: Scarabaeidae) in the laboratory and
      sugarcane fields.
AB  - A serious sugarcane pest, Dasylepida ishigakiensis, remains in the soil during
      most of its life cycle except for a short period for mating. Mating disruption by
      an artificial release of the sex pheromone (R)-2-butanol (R2B), therefore, may be
      a feasible method to control this pest. We examined the effects of artificial
      release of R2B and its related compounds, (S)-2-butanol (S2B) and the racemic 2
      butanol (rac-2B), on the mating success of this beetle both in the laboratory and
      in the field. In flight tunnel experiments, almost all males orientated towards a
      R2B-releasing source and 40% of them landed on the source. When the atmosphere
      was permeated with R2B, the frequency of males landing on the model was
      significantly reduced. Both rac-2B and S2B were less effective, but substantial
      reduction in landing success by males was achieved at higher rac-2B
      concentrations. R2B released from polyethylene dispensers in sugarcane plots
      greatly reduced not only the proportion of females mated with males but also the
      number of males caught by R2B-baited traps, indicating that male mate-searching
      behaviour was strongly affected by the released R2B. Similar inhibitory effects
      on male behaviour were also observed when tube- or rope-type dispensers released
      high rac-2B concentrations in the field. These results indicate that it would be
      highly possible to control D. ishigakiensis through the disruption of the sexual
      communication by releasing either synthetic R2B or rac-2B.

PMID- 21944471
TI  - Neuromuscular junction formation between human stem cell-derived motoneurons and
      human skeletal muscle in a defined system.
AB  - Functional in vitro models composed of human cells will constitute an important
      platform in the next generation of system biology and drug discovery. This study
      reports a novel human-based in vitro Neuromuscular Junction (NMJ) system
      developed in a defined serum-free medium and on a patternable non-biological
      surface. The motoneurons and skeletal muscles were derived from fetal spinal stem
      cells and skeletal muscle stem cells. The motoneurons and skeletal myotubes were
      completely differentiated in the co-culture based on morphological analysis and
      electrophysiology. NMJ formation was demonstrated by phase contrast microscopy,
      immunocytochemistry and the observation of motoneuron-induced muscle contractions
      utilizing time-lapse recordings and their subsequent quenching by d-Tubocurarine.
      Generally, functional human based systems would eliminate the issue of species
      variability during the drug development process and its derivation from stem
      cells bypasses the restrictions inherent with utilization of primary human
      tissue. This defined human-based NMJ system is one of the first steps in creating
      functional in vitro systems and will play an important role in understanding NMJ
      development, in developing high information content drug screens and as test beds
      in preclinical studies for spinal or muscular diseases/injuries such as muscular
      dystrophy, Amyotrophic lateral sclerosis and spinal cord repair.

PMID- 21944473
TI  - Synthesis and biological activities of triazole derivatives as inhibitors of InhA
      and antituberculosis agents.
AB  - InhA, the enoyl reductase from the mycobacterial type II fatty acid biosynthesis
      pathway, is a target for the development of novel drugs against tuberculosis. We
      exploited copper-catalyzed [3+2] cycloaddition between alkynes and different
      azides to afford 1,4-disubstituted triazole or alpha-ketotriazole derivatives.
      Several compounds bearing a lipophilic chain mimicking the substrate were able to
      inhibit InhA. Among them, 1-dodecyl-4-phenethyl-1H-1,2,3-triazole displayed a
      minimum inhibitory concentration inferior to 2 MUg/mL against Mycobacterium
      tuberculosis H37Rv.

PMID- 21944474
TI  - Gait pattern classification in children with Charcot-Marie-Tooth disease type 1A.
AB  - Gait pattern classification may assist in clinical decision making and cluster
      analysis (CA) has been often adopted to this aim. The goal of this study was to
      identify, through CA, typical walking patterns in a group of 21 young subjects
      with CMT1A, a hereditary progressive neuropathy, and to study possible
      correlation with the disease's clinical status. The protocol included
      kinematic/kinetic analysis of natural walking and more demanding locomotor tasks,
      i.e. toe- and heel-walking. Hierarchical cluster analysis was carried out on
      parameters related to primary signs (foot-drop and push-off deficit) and,
      separately, to compensatory mechanisms at proximal (pelvis, hip and knee) or
      distal (ankle) level. CA on primary signs during natural walking identified three
      clusters: (1) pseudo-normal patients (PN), not significantly different from
      controls; (2) patients showing only foot-drop (FD); (3) patients with foot-drop
      and push-off deficit (FD&POD). Patients belonging to the PN subgroup showed
      distal abnormalities during heel-walking. The FD&POD subgroup was associated to a
      significantly worse clinical score (CMTES, p<0.05). The main compensatory
      strategies, which occurred independently from primary clusterization, included
      augmented hip/knee flexion in swing (steppage) and early ankle plantarflexion at
      mid stance (vaulting). We concluded that, although a number of young CMT1A
      patients do not show typical primary deviations during natural walking, they do
      show significant abnormalities in more demanding locomotor tasks that should be
      therefore considered. It is also hypothesized that progression of this
      degenerative condition may be associated to the migration of patients to more
      severe clusters, with possible appearance of compensatory strategies.

PMID- 21944475
TI  - Transitioning to a narrow path: the impact of fear of falling in older adults.
AB  - BACKGROUND: Everyday ambulation requires navigation of variable terrain,
      transitions from wide to narrow pathways, and avoiding obstacles. While the
      effect of age on the transition to a narrow path has been examined briefly,
      little is known about the impact of fear of falling on gait during the transition
      to a narrow path. The purpose was to examine the effect of age and fear of
      falling on gait during transition to a narrow path. METHODS: In 31 young, mean
      age=25.3 years, and 30 older adults, mean age=79.6 years, step length, step time,
      step width and gait speed were examined during usual and transition to narrow
      pathway using an instrumented walkway. FINDINGS: During the transition to narrow
      walk condition, fearful older adults compared to young had a wider step width
      (0.06 m vs 0.04 m) prior to the narrow path and took shorter steps (0.53 m vs
      0.72 m; p<0.001). Compared to non-fearful older adults, fearful older adults
      walked slower and took shorter steps during narrow path walking (gait speed:
      1.1m/s vs 0.82 m/s; p=0.01; step length: 0.60 m vs 0.47 m; p=0.03). In young and
      non-fearful older adults narrow path gait was similar to usual gait. Whereas
      older adults who were fearful, walked slower (0.82 m/s vs 0.91 m/s; p=0.001) and
      took shorter steps (0.44 m vs 0.53 m; p=0.004) during narrow path walking
      compared to usual walking. INTERPRETATION: Changes in gait characteristics with
      transitioning to a narrow pathway were greater for fear of falling than for age.

PMID- 21944476
TI  - Walking while talking: investigation of alternate forms.
AB  - The aim of this study was to develop alternate forms of the walking while talking
      (WWT) dual task, and to determine whether beginning the WWT in mid-alphabet vs.
      at the beginning of the alphabet, affects task outcomes. Alternate test forms
      help reduce practice effects leading to more precise estimates of change over
      time. We conducted a cross-sectional study in 145 community-residing older adults
      (mean age, 79.2 +/- 6.8 y) without dementia or depression. Subjects performed
      four WWT trials with a different initial letter (a, b, m or n). There were no
      differences in velocity, correct letters, or errors on WWT trials beginning at
      shared points in the alphabet ('a' compared to 'b' and 'm' compared to 'n').
      However, trials initiating with letters from the beginning of the alphabet
      compared to mid-alphabet showed significant differences (with higher number of
      correct letters and fewer errors for 'a' and 'b' trials) but not for velocity.
      Thus, starting WWT in mid-alphabet is different from starting at the beginning of
      the alphabet. Alternate forms of the WWT with two separate initial letters from a
      shared point of the alphabet (specifically 'a' and 'b' or 'm' and 'n') may be
      used upon repeated administration to reduce practice effects.

PMID- 21944477
TI  - Concurrent validation of a magnetometer-based step counter in various walking
      surfaces.
AB  - BACKGROUND AND AIM: Clinicians need a simple method for quantifying gait
      activity. The aim of this study was to develop and validate the reliability of a
      quantitative gait assessment based exclusively on one magnetometer located on the
      shank. METHODS: Twenty-five healthy volunteers were simultaneously equipped with
      a magnetometer (MAG system) on the right shank, and two validated step-counter
      systems: the StepWatch Activity Monitor (SAM) and three Force-Sensing Resistors
      (FSRs). Volunteers performed a standard circuit including level walking, up and
      down stairs and up and down a slope. The three step counting approaches were
      compared using the Pearson correlation coefficient and the Bland-Altman method
      for each of the surface-types. RESULTS: The step counts measured by the MAG and
      FSR were highly correlated for all the surfaces (r>.83). Congruently, the Bland
      Altman analysis revealed an overall +/- 5% limit of agreement. The step counts
      measured by the MAG and SAM were also well correlated for the level-surface
      condition (r=.85), with a Bland-Altman +/- 5% limit of agreement but comparisons
      were less satisfying for the other surfaces. CONCLUSIONS: These results
      demonstrate that the use of a single magnetometer is an accurate tool for step
      counting over varied surfaces. These small sensors are easy to set up and to use
      and the signal processing is robust, making the MAG method highly applicable for
      clinical purposes, especially for the analysis of long walking periods in daily
      life conditions.

PMID- 21944478
TI  - The effects of muscle strength on center of pressure-based measures of postural
      sway in obese and heavy athletic individuals.
AB  - INTRODUCTION: Obesity affects postural sway during normal quiet standing;
      however, the reasons for the increased postural sway are unknown. Improving
      muscular strength is regarded as a potential way to improve postural control,
      particularly for obese and overweight subjects. The purpose of this investigation
      is to evaluate the role of muscular strength on postural sway in obese and
      overweight individuals. METHODS: Fifteen healthy weight (control group),
      seventeen obese (obese group) subjects and nine football players (heavy athletic
      group) participated in this investigation. Isometric knee extension force and
      postural sway were measured. Muscular strength was calculated in absolute
      measures as well as relative to body mass (muscular strength to body mass).
      RESULTS: The heavy athletic group demonstrated significantly stronger (absolute)
      lower limb strength (1593.9 N (95% CI 1425.5, 1762.3)) than both the obese
      (796.2N (95% CI 673.8, 824.5)) and control (694.1N (95% CI 563.7, 824.5)) groups.
      As well, when muscular strength was expressed as a ratio to body mass the heavy
      athletic group had significantly higher values (1.27 (95% CI 1.11, 1.43)) than
      obese (0.78 (95% CI 0.66, 0.89) and control (1.00 (95% CI (0.88, 1.12))
      individuals. Despite this, they swayed similarly to the obese (mean center of
      pressure speed of 0.83 cms(-1) (95% CI 0.72, 0.93) vs. 0.87 cms(-1) (95% CI 0.80,
      0.95)), that is, significantly more than the controls (0.60 cms(-1) (95% CI 0.52,
      0.68)). CONCLUSION: Isometric knee extensor strength has a minimal effect on
      postural sway in heavier athletic individuals during normal quiet stance.

PMID- 21944479
TI  - Protective role of cyclooxygenase (COX)-2 in experimental lung injury: evidence
      of a lipoxin A4-mediated effect.
AB  - BACKGROUND: Polymorphoneutrophils (PMNs) are activated by inflammatory mediators
      following splanchnic ischemia/reperfusion (I/R), potentially injuring organs such
      as the lung. As a result, some patients develop respiratory failure following
      abdominal aortic aneurysm repair. Pulmonary cyclooxygenase (COX)-2 protects
      against acid aspiration and bacterial instillation via lipoxins, a family of
      potent anti-inflammatory lipid mediators. We explored the role of COX-2 and
      lipoxin A(4) in experimental I/R-mediated lung injury. MATERIALS AND METHODS:
      Sprague-Dawley rats were assigned to one of the following five groups: (1)
      controls; (2) aortic cross-clamping for 45 min and reperfusion for 4 h (I/R
      group); (3) I/R and SC236, a selective COX-2 inhibitor; (4) I/R and aspirin; and
      (5) I/R and iloprost, a prostacyclin (PGI(2)) analogue. Lung injury was assessed
      by wet/dry ratio, myeloperoxidase (MPO) activity, and bronchoalveolar lavage
      (BAL) neutrophil counts. BAL levels of thromboxane, PGE(2), 6-keto-PGF(1)alpha (a
      hydrolysis product of prostacyclin), lipoxin A(4), and 15-epi-lipoxin A(4) were
      analyzed by enzyme immunoassay (EIA). Immunostaining for COX-2 was performed.
      RESULTS: I/R significantly increased tissue MPO, the wet/dry lung ratio, and
      neutrophil counts. These measures were significantly further aggravated by SC236
      and improved by iloprost. I/R increased COX-2 immunostaining and both PGE(2) and
      6-keto-PGF(1alpha) levels in BAL. SC236 markedly reduced these prostanoids and
      lipoxin A(4) compared with I/R alone. Iloprost markedly increased lipoxin A(4)
      levels. The deleterious effect of SC236 and the beneficial effect of iloprost was
      associated with a reduction and an increase, respectively, in lipoxin A(4)
      levels. CONCLUSIONS: Lipoxin A(4) warrants further evaluation as a mediator of
      COX-2 regulated lung protection.

PMID- 21944480
TI  - Attack the tumor counterattack-c-FLIP expression in Jurkat-T-cells protects
      against apoptosis induced by coculture with SW620 colorectal adenocarcinoma
      cells.
AB  - BACKGROUND: Cancer development relies on a variety of mechanisms that facilitate
      tumor growth despite the presence of a functioning immune system, employing
      different mechanisms to escape immune rejection. Tumors may eliminate tumor
      infiltrating lymphocytes and suppress anti-tumor immune responses, a process
      called "tumor counterattack," based on activation-induced cell death via the
      FAS/FAS-ligand system. To overcome this tumor-cell survival strategy, we examined
      the hypothesis that the sensitivity of FAS mediated apoptosis of Jurkat-T-cells
      can be suppressed by FLIP transfection of Jurkat-T-cells. MATERIALS AND METHODS:
      Jurkat-T-cells were transfected with the FLICE-inhibitory protein FLIP in order
      to bestow them with a resistance to FAS-receptor-mediated apoptosis. FLIP
      transfected and non-transfected Jurkat-T-cells were grown in coincubation with
      SW620 cells and the rates of apoptosis measured via FACS-analysis of Annexin-V.
      RESULTS: First, the tumor-counterattack described in the literature was
      confirmed. About 20% of Jurkat-T-Cells underwent apoptosis in coculture with
      SW620 cells. After coincubation of SW620 cells with FLIP transfected Jurkat-T
      cells the apoptotic rate was significant reduced at levels below 4%. CONCLUSION:
      Transfection of Jurkat-T-cells with FLIP reduces the sensitivity of Jurkat-T
      cells to FAS-mediated apoptosis and may lead to an improved capability to
      antagonize the inherent tumor survival strategy of SW620 cells.

PMID- 21944481
TI  - Contained ruptured paravisceral aortic aneurysm related to immunoglobulin G4
      aortitis.
AB  - BACKGROUND: To describe a case of autoimmune inflammatory abdominal aortic
      aneurysm (AAA) associated with rupture. METHODS: A 63-year-old woman presented
      with 5 days of abdominal pain, malaise, fever, and chills after 6 months of
      debilitating back pain with a 3-kg weight loss. On examination, she was shown to
      have a tender palpable pulsatile abdominal mass. Computed tomographic angiography
      revealed a multilobulated paravisceral AAA (5.5 cm in maximal diameter) and
      bilateral popliteal aneurysms. The appearance of the aneurysms was indicative of
      primary aortic infection. Laboratory examinations demonstrated a white blood cell
      (WBC) count of 12.3*10(9)/L, erythrocyte sedimentation rate of 131 mm/hr, normal
      antinuclear antibody level, and C-reactive protein level of 211 mg/L. Nuclear WBC
      scan showed no uptake of tracer around the aorta. Blood and urine cultures were
      negative. Because of the AAA size and symptoms, open repair was expedited. The
      operation was performed through a transabdominal midline incision with a
      mediovisceral rotation. Extensive retroperitoneal inflammation extending into the
      paravisceral aorta was encountered. Supraceliac clamping was possible. The aorta
      was replaced from the level of the superior mesenteric artery to the aortic
      bifurcation with a 16-mm rifampin-soaked graft with reimplantation of the left
      renal artery. Cultures and biopsies were done. RESULTS: Histology demonstrated
      vessel wall rupture, adventitial fibrosis and inflammatory cell infiltration,
      obliterative phlebitis, lymphoid follicles, perineural inflammation, and
      immunoglobulin G4 (IgG4) plasma cell infiltration, consistent with a contained
      ruptured aneurysm associated with IgG4 periaortitis. The patient had a long
      postoperative course with prolonged intubation and renal failure requiring
      hemodialysis, which resolved 8 weeks postoperatively. Immunosuppression was
      paramount for her improvement. CONCLUSION: IgG4-related inflammatory AAAs are
      rare; this is the first report of one with a contained rupture. The patient's
      symptoms, the unusual appearance on computed tomography, the presence of
      popliteal aneurysms in a woman, and the normal WBC scan were indicative of an
      inflammatory etiology. Tissue biopsy was critical to obtain histological
      diagnosis and direct treatment.

PMID- 21944482
TI  - Comfort effects of a new car headrest with neck support.
AB  - This paper describes the design of a neck-/headrest to increase car comfort. Two
      studies were undertaken to create a new comfortable headrest with neck support.
      In experiment one, neck- and headrest data were gathered using 35 test subjects.
      The pressure distribution, stiffness of the foam material and position of the
      head and neck support were determined. In experiment two a full adjustable final
      headrest with adjustable neck support was constructed and tested with 12 subjects
      using a new adjustable headrest under virtual reality driving conditions.
      Experiment two showed that the headrest with the new/adjustable neck support was
      favoured by the majority of the subjects. 83% were satisfied with the stiffness
      of the material. 92% were satisfied with the size of the neck- and headrest. All
      subjects mentioned that the neck support is a comfort benefit in calm traffic
      conditions or on the motorway.

PMID- 21944483
TI  - Medication errors and secondary victims.

PMID- 21944484
TI  - [Recognition and editorial farewell].

PMID- 21944485
TI  - [Sensitivity to animals' allergens in people working with animals].
AB  - BACKGROUND: Animals with fur or feathers can induce IgE-mediated reactions. From
      10 to 30% of workers in laboratory animals may develop allergic symptoms by
      exposing to them. OBJECTIVE: To determine the frequency of sensitization to
      animal allergens extracts in workers of the Bioterio of the Autonomous University
      of Puebla. MATERIAL AND METHODS: It is an observational, transversal and
      descriptive study, 29 subjects with animal-related professional activities were
      included. We performed a standardized clinical history and applied skin prick
      tests with allergen extracts of rat, mouse, guinea pig, rabbit, hamster, dog,
      cat, cattle, goat and horse hair. RESULTS: Twenty-nine subjects were included in
      the study, mean age 32.3 years, male predominance (82.8%) and years of work 6.3.
      Laboratory animal workers were exposed mostly to dogs (83%). Nearly half of the
      workers reported clinical manifestations at work. Sixty-two percent of them had
      at least one positive skin test to animal allergen extracts. No statistically
      significant association between history of atopy, seniority, clinical
      manifestations and positive skin tests to any allergen extract was found.
      CONCLUSIONS: The majority of animal laboratory workers was found allergic to
      animal allergens. No statistically significant association was present between
      the clinical manifestations, hypersensitivity to any animal allergen extract,
      seniority and history of atopy. Therefore, we recommend monitoring of animal
      allergy for an early detection and proper treatment in laboratory animal workers.

PMID- 21944486
TI  - [Autoantibodies in GAD65 in Mexican adults with diabetes types 1 and 2 and their
      siblings].
AB  - BACKGROUND: Pancreatic cell destruction causing type 1 diabetes is associated to
      diverse autoantibodies. Antibodies against glutamic acid decarboxylase have been
      found in type 1 (DM1) and type 2 diabetic patients (DM2). Their presence in
      siblings is unknown. OBJECTIVE: To determine the presence of anti-GAD65
      autoantibodies in diabetic patients and their siblings. PARTICIPANTS AND METHOD:
      Sixty-eight individuals were included and distributed in four groups: group 1
      DM1, group 2 DM2, group 3 and 4 healthy siblings of patients from groups 1 and 2.
      Anti-GAD65, peptide C, serum glucose, total cholesterol and triglycerides were
      obtained. Body mass index and hip-waist ratio were measured. RESULTS: Anti-GAD65
      antibodies were positive in 23% of DM1, in 14% of DM2, and in 7.7% and 9.5% in
      siblings of both groups, respectively. Using Mann-Whitney's U the mean of anti
      GAD65 in diabetic type 1 and 2 patients was p = 0.022; between DM1 and their
      siblings and between DM2 and their siblings there was no statistical
      significance. C peptide was low in cases of positive anti-GAD65 of DM1 and DM2;
      and it was normal in patients with negative anti-GAD65. CONCLUSIONS: Anti-GAD65
      autoantibodies are more frequent in type 1 diabetic patients. There were no
      meaningful differences regarding the presence of anti-GAD65 in patients and their
      siblings.

PMID- 21944487
TI  - [Skin prick tests with standardized extracts of mites of different precedence in
      patients with asthma and allergic rhinitis].
AB  - BACKGROUND: House dust mites are important airborne allergens worldwide,
      particularly in the tropical environment. OBJECTIVE: To assess sensitization of
      allergic patients to different mite species in the Cuban city of Camaguey; as
      well as to compare standardized allergen extracts from different sources by skin
      prick tests. PATIENTS AND METHOD: Skin prick tests were performed in 60 patients
      with asthma and/or allergic rhinitis and in 60 non-allergic volunteers, ranging
      from 2 to 76 years old. In both groups, Diater-Prick lancets were used, together
      with Valergen extracts (Biocen, Cuba) at 20,000 BU/mL and Diater extracts
      (Argentina) at 50,000 UBE/PNU/mL. RESULTS: The highest values of sensitization
      prevalence using Diater extracts were seen in Dermatophagoides pteronyssinus
      (Dp), Dermatophagoides farinae (Df), and Blomia tropicalis (Bt) in allergic
      patients and in non-allergic controls. Diagnostic sensitivity values were: Dp,
      79; Df, 84; Bt, 84 and B. kulagini, 83%. Specificity varied from 72 to 85%. On
      the other hand, with Biocen extracts, the highest positivity was noted in Dp and
      D. siboney (Ds). Sensitivity values were 78% (Dp); 78% (Ds) and 82% (BT).
      Specificity values ranged from 79 to 82%. CONCLUSIONS: The standardized allergen
      extracts from the assessed laboratories induced similar values of sensitivity and
      specificity.

PMID- 21944488
TI  - [Allergy to materials used in dental procedures].
AB  - OBJECTIVE: To provide a review of the literature regarding the pathological
      effects of material used in clinical dentistry. DATA SOURCES: PubMed search was
      performed using the key words: dental biomaterial, odontologic toxicity,
      odontologic allergy, dental allergens, dental resins. STUDY SELECTION: Articles
      were selected based on their relevance to this topic. RESULTS: The biomaterials
      used in orthodontic or dental treatment may lead to alterations of greater
      biological importance in susceptible or sensitized individuals, and may be able
      to alter the functions of cells in the mouth, including dentinogenesis and tissue
      repair; toxicity and mutagenicity have been observed. Some of them release
      potential antigens or allergens capable of inducing immune or immediate and
      delayed allergic reactions of diverse severity and extension, which may include
      extraoral damage. CONCLUSIONS: The number of patients with pathology originated
      by dental materials has increased. The scarce knowledge about it delays
      diagnosis. The study of biomaterials used in odontologic procedures and its
      harmful effect must be encouraged, as well as its pathological manifestations
      which require more clinical investigation and diffusion, with the aim to give
      more and better information to dentists, family and allergy physicians so that
      they can provide prompt and successful care.

PMID- 21944489
TI  - Transfer factor and allergy.
AB  - Although various mechanisms involving antibodies and various cell types
      participate, a Thl and Th2 cells imbalance seems to play a central role for
      allergy development. Other lymphocyte subpopulations, such as Th17, CD4 FOXP3,
      and Th9 positive regulatory T lymphocytes may also be involved in the allergic
      response. Regulatory processes are an appealing target for therapeutic approaches
      aiming to solve allergic reactions by restoring the delicate balance within the
      immune system. Transfer factor (TF) or dialyzable leukocyte extract is meant to
      transfer cell-mediated immunity from immune competent donors to unsensitized or
      deficient recipients. A PubMed search on the current knowledge on TF indicates
      that TF may restore the Th1/Th2 balance and improve immune regulatory mechanisms
      of patients receiving it. Our preliminary results demonstrate that TF induces
      mRNA expression of IFN-g, osteopontin, RANTES, and hBD-2 in human healthy
      subjects. TF has been used to treat a variety of immune dysfunction related
      pathologies, such as allergy, autoimmunity, immunodeficiencies, infectious
      diseases and tumors. Patients receiving TF together with their conventional
      treatment often have better clinical evolution than without it, as we have
      witnessed, adding TF to the usual medical treatment of allergic diseases as an
      attempt to provide allergic patients with those regulatory elements that they
      apparently lack but require to achieve properly regulated immune responses and
      thus obtain a faster and better resolution of allergic reactions.

PMID- 21944490
TI  - Correlation between laparoscopic and histopathologic diagnosis of endometriosis.
AB  - OBJECTIVE: To review the histopathologic diagnosis of biopsies taken following
      visualization of endometriosis at laparoscopy and to correlate visual with
      microscopic diagnoses. METHODS: A retrospective review was undertaken of medical
      charts with a diagnosis of endometriosis at Aga Khan University Hospital,
      Nairobi, Kenya, between January 2001 and October 2010. Eligibility included
      visual diagnosis of endometriosis at laparoscopy, with a clear record of site,
      size, morphology, and number of lesions. The histopathologic diagnosis of the
      biopsies sampled was sought. Correlation was undertaken using kappa statistics
      for diagnostic variability. RESULTS: Of the 204 relevant records, 152 (74.5%) met
      the eligibility criteria; from these cases, 239 specimens were submitted for
      histology. The most common symptom was chronic pelvic pain (108 [71.1%]). Most
      biopsies were obtained from the ovary and posterior cul-de-sac. Histopathologic
      diagnosis was confirmed in (152 [63.8%]) specimens and correlated with Asian
      race, multiparity, and chronic pelvic pain. Neither the site of the lesion nor
      the stage of disease influenced the histopathologic diagnosis. CONCLUSION:
      Laparoscopic visualization of endometriosis does not always correlate with
      histopathologic diagnosis; several other lesions may mimic endometriosis on
      histopathologic examination.

PMID- 21944491
TI  - Crystal morphology study of N,N'-diacetylchitobiose by molecular dynamics
      simulation.
AB  - Bisphenoidal shape of alpha-N,N'-diacetylchitobiose (alpha-(GlcNAc)(2))
      monohydrate crystals was obtained from aqueous solution. Crystal morphology was
      studied by computer simulation. Theoretical morphologies calculated by classic
      models (a BFDH model, a surface free-energy method, and an AE model) deviated
      significantly from that from the experimental crystal habit. Therefore, a solvent
      effect was considered by introducing an interface layer model based on molecular
      dynamics simulation in order to bridge this gap. The results of the simulation
      showed that the calculated habit is much closer to the experiment, meaning that
      the interface layer model describes the solvent effect very well. This model may
      also be applied for other oligosaccharide systems to study the relationship among
      crystal morphology, crystal structure, and solvation effects.

PMID- 21944492
TI  - Reprint of: Simulation Platform: a cloud-based online simulation environment.
AB  - For multi-scale and multi-modal neural modeling, it is needed to handle multiple
      neural models described at different levels seamlessly. Database technology will
      become more important for these studies, specifically for downloading and
      handling the neural models seamlessly and effortlessly. To date, conventional
      neuroinformatics databases have solely been designed to archive model files, but
      the databases should provide a chance for users to validate the models before
      downloading them. In this paper, we report our on-going project to develop a
      cloud-based web service for online simulation called "Simulation Platform".
      Simulation Platform is a cloud of virtual machines running GNU/Linux. On a
      virtual machine, various software including developer tools such as compilers and
      libraries, popular neural simulators such as GENESIS, NEURON and NEST, and
      scientific software such as Gnuplot, R and Octave, are pre-installed. When a user
      posts a request, a virtual machine is assigned to the user, and the simulation
      starts on that machine. The user remotely accesses to the machine through a web
      browser and carries out the simulation, without the need to install any software
      but a web browser on the user's own computer. Therefore, Simulation Platform is
      expected to eliminate impediments to handle multiple neural models that require
      multiple software.

PMID- 21944493
TI  - Generation of feeder-free pig induced pluripotent stem cells without Pou5f1.
AB  - The pig represents an ideal large-animal model, intermediate between rodents and
      humans, for the preclinical assessment of emerging cell therapies. As no
      validated pig embryonic stem (pES) cell lines have been derived so far, pig
      induced pluripotent stem cells (piPSCs) should offer  an alternative source of
      undifferentiated cells to advance regenerative medicine research from bench to
      clinical trial. We report here for the first time the derivation of piPSCs from
      adult fibroblast with only three transcription factors: Sox2 (sex determining
      region Y-box 2), Klf4 (Kruppel-like  factor 4), and c-Myc (avian myelocytomatosis
      viral oncogene homolog). We have been able to demonstrate that exogenous Pou5f1
      (POU domain class 5 transcription factor 1; abbreviated as Octamer-4: Oct4) is
      dispensable to achieve and maintain pluripotency in the generation of piPSCs. To
      the best  of our knowledge, this is also the first report of somatic
      reprogramming in any species without the overexpression, either directly or
      indirectly, of Oct4. Moreover, we were able to generate piPSCs without the use of
      feeder cells, approaching thus xeno-free conditions. Our work paves the way  for
      the derivation of clinical grade piPSCs for regenerative medicine.

PMID- 21944494
TI  - Intraoral high condylotomy for a case of chronic mandibular dislocation.

PMID- 21944495
TI  - Not the same key for all the locks: Re: Reasons for delayed presentation in oral
      and oropharyngeal cancer: the patients' perspective.

PMID- 21944496
TI  - Use of in-house, full-colour printed three-dimensional model for training in
      endoscopic periradicular surgery for molar radicular cyst.

PMID- 21944497
TI  - Pelvic sepsis after transanal endoscopic microsurgical excision of rectal polyps.

PMID- 21944498
TI  - Laparoscopic treatment of a Meckel's diverticulum.

PMID- 21944499
TI  - Assessment of time and cost of anesthesia with versus without recurrent laryngeal
      nerve monitoring in patients undergoing total thyroidectomy.

PMID- 21944500
TI  - Tailgut cysts: what is the best surgical approach?

PMID- 21944501
TI  - Pellet venous embolism from a destructive shotgun injury.

PMID- 21944502
TI  - Single-incision laparoscopic surgery for intra-abdominal metastatic melanoma.

PMID- 21944503
TI  - An innovative technique for intra-abdominal abscess drainage using a sump drain
      by trocar puncture.

PMID- 21944504
TI  - Successful application of the vacuum-assisted closure system in delayed primary
      closure: a case of gastrointestinal perforation.

PMID- 21944505
TI  - Laparoscopic repair of a septum transversum hernia in an adult.

PMID- 21944506
TI  - Granulomatous stump appendicitis mimicking Crohn's disease.

PMID- 21944507
TI  - Risk factors for pancreatic fistula after stapled gland transection.
AB  - The objective of this study was to identify risk factors for pancreatic fistula
      (PF) after stapled transection in distal pancreatectomy (DP). Patients undergoing
      DP using a stapler for transection between 2005 and 2009 were identified from a
      pancreatic resection database. Variables  examined included patient and tumor
      characteristics, staple size, and the use of mesh reinforcement. Univariate and
      multivariate regression analyses were performed to identify risk factors for
      postoperative PF. One hundred forty-nine had stapled transection, and of these,
      25 (17%) had mesh  reinforcement. The overall morbidity and mortality rates were
      28 per cent and less than 1 per cent; 34 (23%) were diabetic. The rate of
      clinically significant PF was 14 per cent. On univariate analysis, diabetes (P =
      0.04), a firm pancreas (P = 0.03), use of mesh staple line  reinforcement (P =
      0.02), use of a 4.1-mm staple cartridge (P = 0.01), and blood loss greater than
      100 mL (P = 0.01) were associated with higher pancreatic fistula rates. On
      multivariate analysis, only the presence of diabetes (OR, 4.17; 95% CI, 1.1-15.3;
      P  = 0.03) and the use of a 4.1-mm cartridge (OR, 8.57; 95% CI, 1.2-60.2; P =
      0.03) were independently associated with pancreatic fistula formation. Stapled
      pancreatic transection provides an acceptable PF rate after DP. Diabetes and
      staple size influence PF rates. In our experience,  use of mesh staple line
      reinforcement did not reduce the incidence of PF after stapled transection.

PMID- 21944508
TI  - Outcomes of emergent incisional hernia repair.
AB  - This study examines the effect of emergent repair on incisional hernia repair
      outcomes at 16 Veteran's Affairs Medical Centers between 1998 and 2002. Of the
      1452 cases reviewed, 63 (4.3%) were repaired emergently. Patients undergoing
      emergent repair were older (P = 0.02), more  likely to be black (P = 0.02), and
      have congestive heart failure (P = 0.001) or chronic obstructive pulmonary
      disease (P = 0.001). Of emergent repairs, 76.2 per cent involved intestinal
      incarceration versus 7.2 per cent of elective repairs (P < 0.0001),  and 17.5 per
      cent had concomitant bowel resection compared with 3.9 per cent of elective cases
      (P < 0.0001). Patients undergoing emergent repair were also more likely to
      receive primary suture repair (49.2 vs 31.1%, P = 0.003), develop a postoperative
      complication (26.0  vs 11.3%, P = 0.002), and have increased postoperative length
      of stay (7 vs 4 days, P < 0.0001). There were nine (14.3%) deaths at 30 days for
      the emergent group compared with 10 (0.7%) in the elective group (P < 0.001).
      However, there was no significant  difference between emergent and elective
      repairs in long-term complications. Emergent hernia repair is associated with
      increased mortality rates, early complications, and longer length of stay;
      however, long-term outcomes are equivalent to elective cases. These data suggest
      that technical  outcomes for emergent repairs approach those of elective
      operations.

PMID- 21944509
TI  - Predictors of fatal outcome after colectomy for fulminant Clostridium difficile
      Colitis: a 10-year experience. dr.markelov@gmail.com.
AB  - Surgical treatment of fulminant Clostridium difficile colitis has high mortality
      rates. Identification of a set of preoperative characteristics that could predict
      outcome after surgery is necessary to optimize clinical management and guide
      surgical timing. Data were retrospectively  collected on patients operated on for
      C. difficile colitis between 2000 and 2010 at our institution. Statistical
      analysis was performed to identify predictors of mortality. We reviewed the
      records of 13 inpatients diagnosed as having C. difficile colitis and who
      underwent colectomy  during the same admission. The in-hospital mortality rate
      for patients undergoing colectomy for colitis was 46.2 per cent. Independent
      predictors of mortality included the following: white blood cell count
      (34,600/MUL or greater), hypoalbuminemia (1.5 g/dL or less), septic shock with
      requirements  of vasopressors, and respiratory failure. Patients who underwent
      colectomy earlier (mean time from presentation to surgery 2.4 +/- 1.5 days) had
      decreased mortality (P = 0.019).). Longer length of hospital stay to the time of
      diagnosis was associated with higher rates of fatal  outcome (P = 0.031).
      Parameters without significant difference (P > 0.05) included patient age,
      presenting symptoms, other comorbidities, creatinine levels, and CT scan
      findings. Identified factors can predict unfavorable outcomes after colectomy.
      Aggressive surgical intervention  early in the course of the disease might be
      associated with improved survival.

PMID- 21944510
TI  - Prolonged (longer than 3 hours) laparoscopic cholecystectomy: reasons and
      results.
AB  - For the experienced surgeon, the average operative time for a laparoscopic
      cholecystectomy is less than 1 hour. There has been no study documenting the
      causes and results of prolonged (longer than 3 hours) surgery. A retrospective
      study was done of patients who underwent cholecystectomy  between January 2003
      and December 2007. A total of 3126 cholecystectomies were done. After excluding
      patients who had a planned open cholecystectomy and patients who had additional
      laparoscopic surgeries, we identified 70 patients who had a planned laparoscopic
      cholecystectomy with operative  time exceeding 3 hours. Multivariate stepwise
      logistic regression was performed analyzing the various factors leading to
      prolonged surgery. Of the 70 patients, ranging in age from 21 to 92 years (mean,
      57 years), most (n = 53) were female. Operative time ranged from 3 hours to 6
      hours 40 minutes  (mean, 3 hours 37 minutes). Emergency:elective admission ratio
      was 9:5 and acute cholecystitis (n = 40) was the most common indication. Common
      characteristics were obesity (n = 44, P = 0.031), intra-abdominal adhesions (n =
      43, P = 0.004), and previous abdominal surgeries (n  = 40, P = 0.002).
      Intraoperative complications included spillage of stones (n = 6), bile duct
      injury (n = 3), and bleeding (n = 3). The possibility of prolonged laparoscopic
      cholecystectomy should be anticipated in patients with obesity and previous
      abdominal operations. Prolonged surgery  increases the risk of complications
      (bile duct injury, bleeding) and prolongs the postoperative hospital stay.

PMID- 21944511
TI  - Biliary obstruction during cholecystectomy: endoscopic retrograde
      cholangiopancreatography, evade, or explore?
AB  - Biliary obstruction discovered during cholecystectomy remains a challenging
      problem. To determine the best management, this retrospective study compared
      intervention during the same admission (SA) versus delayed/no intervention (DN).
      Furthermore, this study demonstrates the power  of a deidentified research
      database derived from electronic medical records. Patients undergoing
      cholecystectomy and intraoperative cholangiogram (IOC) were identified in the
      Vanderbilt Synthetic Derivative database. Patients with biliary obstruction
      discovered during IOC were included and  a cohort study was performed.
      Interventions for biliary obstruction included endoscopic retrograde
      cholangiopancreatography or common bile duct exploration. A composite measure of
      any biliary complication served as the primary outcome. A total of 1899 patients
      who underwent cholecystectomy  were evaluated; 151 met inclusion criteria. Mean
      age was 44 years with 69 per cent women. Sixty-three per cent of patients had
      intervention during the SA for cholecystectomy compared with 37 per cent for DN.
      Nineteen per cent of patients in the SA group had biliary complications versus 
      16 per cent for DN (P = 0.656). Patients in the SA group had a significantly
      increased length of stay (4.7 vs 2.1 days, P < 0.05). These data suggest an
      aggressive approach to biliary obstruction seen on IOC does not reduce
      postoperative biliary complications and may  incur unnecessary resource use.

PMID- 21944512
TI  - Lymphovascular invasion as a prognostic factor in melanoma.
AB  - The prognostic significance of lymphovascular invasion (LVI) in melanoma remains
      controversial. Clinicopathologic data from a prospective trial of patients with
      melanoma were analyzed with respect to LVI. Disease-free survival and overall
      survival (OS) were evaluated by Kaplan-Meier  (KM) analysis. Univariate and
      multivariate analyses were performed to evaluate factors predictive of tumor
      positive sentinel nodes (SLN) and survival. A total of 2183 patients were
      included in this analysis; 171 (7.8%) had LVI. Median follow-up was 68 months.
      Factors associated with LVI included  tumor thickness, ulceration, and histologic
      subtype (P < 0.05). LVI was associated with a greater risk of SLN metastasis (P <
      0.05). By KM analysis, LVI was associated with worse OS (P = 0.0009). On
      multivariate analysis, age, gender, thickness, ulceration, anatomic  location,
      and SLN status were predictors of OS; however, LVI was not an independent
      predictor of OS. Among patients with regression, the 5-year OS rate was 49.4 per
      cent for patients with LVI versus 81.1 per cent for those with no LVI (P <
      0.0001). LVI is associated with a  greater risk of SLN metastasis. Although LVI
      is not an independent predictor of OS in general, it is a powerful predictor of
      worse OS among patients who have evidence of regression of the primary tumor.

PMID- 21944513
TI  - Errors in administrative-reported ventilator-associated pneumonia rates: are
      never events really so?
AB  - Ventilator-associated pneumonia (VAP) is a common problem in an intensive care
      unit (ICU), although the incidence is not well established. This study aims to
      compare the VAP incidence as determined by the treating surgical intensivist with
      that detected by the hospital Infection Control  Service (ICS). Trauma and
      surgical patients admitted to the surgical critical care service were
      prospectively evaluated for VAP during a 5-month time period. Collected data
      included the surgical intensivist's clinical VAP (SIS-VAP) assessment using
      Centers for Disease Control and Prevention  (CDC) VAP criteria. As part of the
      hospital's VAP surveillance program, these patients' medical records were also
      reviewed by the ICS for VAP (ICS-VAP) using the same CDC VAP criteria. All
      patients suspected of having VAP underwent bronchioalveolar lavage (BAL). The SIS
      VAP and ICS-VAP were  then compared with BAL-VAP. Three hundred twenty-nine
      patients were admitted to the ICU during the study period. One hundred thirty
      three were intubated longer than 48 hours and comprised our study population.
      Sixty-two patients underwent BAL evaluation for the presence of VAP on 89
      occasions.  SIS-VAP was diagnosed in 38 (28.5%) patients. ICS-VAP was identified
      in 11 (8.3%) patients (P < 0.001). The incidence of VAP by BAL criteria was 23.3
      per cent. When compared with BAL, SIS-VAP had 61.3 per cent sensitivity and ICS
      VAP had 29 per cent sensitivity. VAP rates reported  by hospital administrative
      sources are significantly less accurate than physician-reported rates and
      dramatically underestimate the incidence of VAP. Proclaiming VAP as a never event
      for critically ill for surgical and trauma patients appears to be a fallacy.

PMID- 21944514
TI  - Obesity in trauma patients: correlations of body mass index with outcomes, injury
      patterns, and complications.
AB  - Current understanding of the effects of obesity on trauma patients is incomplete.
      We hypothesized that among older trauma patients, obese patients differ from
      nonobese patients in injury patterns, complications, and mortality. Patients
      older than 45 years old presenting to a Level I  trauma center were included in
      this retrospective database analysis (n = 461). Body mass index (BMI) groups were
      defined as underweight less than 18.5 kg/m(2), normal 18.5 to 24.9 kg/m(2),
      overweight 25.0 to 29.9 kg/m(2), or obese greater than 30 kg/m(2).  Injury
      patterns, complications, and outcomes were analyzed using univariate analyses,
      multivariate logistic regression, and Kaplan-Meier survival analysis. Higher BMI
      is associated with a higher incidence of torso injury and proximal upper
      extremity injuries in blunt trauma (n = 410). All  other injury patterns and
      complications (except anemia) were similar between BMI groups. The underweight
      (BMI less than 18.5 kg/m(2)) group had significantly lower 90-day survival than
      other groups (P < 0.05). BMI is not a predictor of morbidity or mortality in
      multivariate  analysis. Among older blunt trauma patients, increasing BMI is
      associated with higher rates of torso and proximal upper extremity injuries. Our
      study suggests that obesity is not an independent risk factor for complications
      or mortality after trauma in older patients. Conversely, underweight  trauma
      patients had a lower 90-day survival.

PMID- 21944515
TI  - Regression does not predict nodal metastasis or survival in patients with
      cutaneous melanoma.
AB  - Controversy exists regarding the prognostic implications of regression in
      patients with cutaneous melanoma. Some consider regression to be an indication
      for sentinel lymph node (SLN) biopsy because regression may result in
      underestimation of the true Breslow thickness. Other data support  regression as
      a favorable prognostic indicator, representing immune system recognition of the
      primary tumor. This analysis was performed to determine whether regression
      predicts nodal metastasis, disease-free survival (DFS), or overall survival (OS).
      Post hoc analysis was performed of a multicenter  prospective randomized trial
      that included patients aged 18 to 70 years with cutaneous melanomas 1 mm or
      greater Breslow thickness. All patients underwent SLN biopsy; those with tumor
      positive SLN underwent completion lymphadenectomy. Kaplan-Meier analysis of
      survival, univariate analysis,  and multivariate analysis were performed. A total
      of 2220 patients (261 with regression; 1959 without regression) were included in
      this analysis with a median follow-up of 68 months. Patients with regression were
      more likely to be male, older than 50 years old, and have lower median Breslow 
      thickness, superficial spreading histologic subtype, and a nonextremity anatomic
      location (P < 0.05 in all cases). Regression was not significantly associated
      with Clark level, ulceration, lymphovascular invasion, number of SLNs removed, or
      SLN metastasis. On multivariate analysis,  factors independently predictive of
      DFS included Breslow thickness, ulceration, and SLN status (P < 0.05 in all
      cases); the same factors along with age, gender, and anatomic tumor location were
      significantly associated with OS (P < 0.05 in all cases). Regression was not 
      significantly associated with DFS (risk ratio [RR], 0.94; 95% confidence interval
      [CI], 0.67-1.27; P = 0.68) or OS (RR, 1.01; 95% CI, 0.76-1.32; P = 0.93). These
      data suggest that regression is not a significant prognostic factor for patients
      with cutaneous melanoma  and should not be used to guide clinical decision-making
      for such patients.

PMID- 21944516
TI  - Laparoscopic cholecystectomy is safe but underused in the elderly.
AB  - Studies confirm that laparoscopic cholecystectomy (LC) is safe and efficacious
      for elderly patients. The purposes of this study were to evaluate if LC is
      underused in the elderly and if it is a safe option in that group. Open
      cholecystectomy (OC) and LC were compared in nonelderly (40  to 64 years) and
      elderly (65 years or older) matched patient groups identified with gallbladder
      disease using the American College of Surgeons National Surgical Quality
      Improvement Program database (2005 to 2008). Length of stay (LOS), 30-day
      complications, and mortality were evaluated as  outcomes. Using multivariate
      logistic regression, independent predictors of OC were identified. After case
      matching, each group had 11,926 patients. A chi(2) test showed that elderly (20.1
      vs 15.0%, P < 0.001) were more likely to undergo OC. Elderly patients had 
      significantly higher comorbidities and were operated on as emergent case (all P <
      0.05). OC had longer LOS and mortality (all P < 0.05). Among 10 other variables
      in logistic regression, elderly had a higher likelihood of receiving OC (OR,
      1.299; P < 0 0.001).  Significant disparity exists between elderly and nonelderly
      patients in use of LC surgery. LC has a lower complication rate than OC; however,
      elderly undergo LC less often. Awareness needs to be raised for offering earlier
      operative intervention and the superior results of LC in the elderly.

PMID- 21944517
TI  - After-hours urgent and emergent surgery in the elderly: outcomes and prognostic
      factors.
AB  - Surgeons are becoming increasingly involved in the care of elderly patients. The
      purpose of this project was to evaluate contemporary outcomes of emergent
      surgeries performed after hours in elderly patients and to determine any risk
      factors for poor outcome. We retrospectively reviewed  patients 80 years or older
      undergoing an urgent or emergent surgery at our medical center from 6 pm to 6 am
      from October 2006 through July 2009. Comparisons were made between survivors and
      nonsurvivors using Wilcoxon rank sum and Fisher exact test when indicated. P <
      0.05 was considered  significant. During the study period, 59 patients met
      inclusion criteria; the average age was 84 years (range, 80 to 102 years). A
      total of 70 procedures were performed; the most common were colectomy (18), small
      bowel resection (13), lysis of adhesions (9), and gastric surgery (8). The
      majority  of patients were female (68%) with 47 per cent and 53 per cent of
      patients undergoing emergent and urgent surgery, respectively. Sixty-seven
      complications occurred in 38 patients; the morbidity rate was 64 per cent, and
      the mortality rate was 25 per cent. The only studied factors significantly 
      associated with mortality were higher American Society of Anesthesiologists score
      (P = 0.004), increased intravenous fluids (P = 0.03), decreased intraoperative
      urine output (P = 0.03), and the need for intraoperative blood (P = 0.003). After
      hours urgent and emergent  surgery in the elderly has a high morbidity and
      mortality rate. We identified several risk factors for a poor prognosis that may
      be useful to the surgeon when discussing the patient's prognosis with the family.

PMID- 21944518
TI  - Lysostaphin-coated mesh prevents staphylococcal infection and significantly
      improves survival in a contaminated surgical field.
AB  - Mesh and wound infections during hernia repair are predominantly caused by
      Staphylococcus aureus. Human acellular dermis (HAD) is known to lose its
      integrity in the face of large bacterial loads. The goal of this study was to
      determine if lysostaphin (LS), a naturally occurring anti-Staphylococcal protein,
      can protect HAD mesh from S. aureus infection. HAD samples, 3 cm * 3 cm, were
      implanted in the onlay fashion on the anterior abdominal wall of rats (n = 75).
      Subjects were grouped based on presence of antimicrobial bound to HAD (none or
      LS) and presence of S. aureus inoculum (sterile, 106, 108 CFU). At 60 days,
      meshes were explanted, and bacterial growth, histology, and mesh tensile strength
      were examined. None of the controls receiving bacterial inoculation without LS
      survived to 60 days. All LS-HAD sterile and LS-106 animals survived to
      explantation. The LS-HAD 108 group had a mortality rate of 50 per cent. All
      surviving LS-treated animals (n = 25) had negative wound and mesh cultures.
      Blinded gross and histologic evaluation and measured tensile strengths between
      all LS groups were comparable. Animals implanted with LS-HAD had a dramatically
      improved rate of survival. All animals surviving to 60 days had completely
      cleared S. aureus from their wounds with maintenance of mesh integrity and
      tensile strength. These findings strongly suggest the clinical use of LS-treated
      mesh in contaminated fields may translate into a more durable hernia repair.

PMID- 21944519
TI  - Impact of pancreatic cancer and subsequent resection on glycemic control in
      diabetic and nondiabetic patients.
AB  - The incidence of new onset or worsening diabetes is surprisingly low in patients
      after partial pancreatectomy for cancer, leading us to question what factors
      predict diminished glycemic control in those undergoing resection. All patients
      undergoing pancreatectomy for cancer at a large,  rural university teaching
      hospital between 1996 and 2010 were identified. The incidence of new onset, or
      worsening, existing diabetes was determined based on pre and postoperative
      medication requirement. Univariate analysis was undertaken to identify factors
      that predict worsened glycemic  control. One hundred and one (1 total, 79
      Whipple, 21 distal) patients were identified, 41 per cent of which had
      preexisting diabetes. Nearly half of existing diabetics manifested an increased
      medication requirement prior to their cancer diagnosis. New onset diabetes
      occurred in 20 per cent  of postoperative patients. Of established diabetics, 34
      per cent had either improved glycemic control (9/41) or were cured (5/41) despite
      the reduction of islet cell mass that occurred with surgery. On univariate
      analysis, only prolonged hospitalization was associated with worsened glycemic 
      control. Diminished glycemic control is a frequent presenting symptom of
      pancreatic cancer. Worsened or new onset diabetes is associated with length of
      stay, which can be influenced by a number of factors including complications and
      comorbidities.

PMID- 21944520
TI  - Central line-associated blood stream infection in the critically ill trauma
      patient.
AB  - Blood stream infections in the critically ill are a common cause of morbidity.
      Strict adherence to sterile technique can reduce central line-associated blood
      stream infections (CLBSIs) and has become a quality improvement measure. We did a
      retrospective review of 6,014 trauma admissions  representing 10,370 catheter
      days. CLBSI was defined as a positive blood culture with central venous access
      without evidence of other infectious sources. Thirty-five CLBSIs were identified
      in the study period (3.26/1,000 line days). The average Injury Severity Score was
      32, the average intensive  care unit stay was 24 days, and the average overall
      length of stay was 34 days, which is higher than that of nonCLBSI patients. In
      25/35 cases, there was a break in sterile technique during central venous
      catheter placement (71%). Of the 25 cases, 16 of them were performed in the
      intensive  care unit (64%), five in the operating room (20%), and four in the
      emergency department (16%). Twenty of the 35 patients with CLBSI (57%) had a
      total of 24 infections, a 2-fold increase in infectious complications for a given
      Injury Severity Score. Seventeen (17) of the 25 "dirty"  central lines (68%) were
      changed within 24 hours in an effort to reduce the risk of CLBSI without success.
      A large percentage of CLBSI can be traced to the initial placement of a central
      venous line under less than ideal sterile technique. Changing a line within 24
      hours may not be sufficient  to reduce the risk of CLBSI. Every effort should be
      made to adhere to proper sterile technique while placing central venous catheter.

PMID- 21944521
TI  - The effects of protocolized use of recombinant factor VIIa within a massive
      transfusion protocol in a civilian level I trauma center.
AB  - Despite conflicting data regarding its effectiveness, many massive transfusion
      protocols (MTPs) include recombinant Factor VIIa (rFVIIa) as an adjunct to
      hemorrhage control. Over a 3-year period, outcome data for massively transfused
      patients was compared based on administration of  rFVIIa as part of a mature MTP.
      Of 228 MTP activations, 117 patients were candidates for rFVIIa, and, of these,
      39 patients received rFVIIa under the MTP. Comparing patients who received rFVIIa
      with those who did not based on initial packed red blood cell (PRBC) transfusion
      requirements, there  was no difference in mortality for transfusions <= 20 units
      (25 vs 24%, 24-hour; 25 vs 42%, 30-day) or 21 to 30 units (33 vs 47%, 24-hour; 55
      vs 50%, 30-day). For initial requirement >= 30 units of PRBCs, 24-hour mortality
      (26 vs 64%, P = 0.02)  was significantly decreased in patients that received
      rFVIIa (n = 19) compared with those who did not (n = 17). These mortality
      differences were not maintained at 30 days (68 vs 71%). rFVIIa had minimal
      clinical impact on outcomes for patients requiring less than 30 units of PRBCs. 
      For patients transfused more than 30 units of PRBCs, differences in 24-hour and
      30-day mortality suggest that rFVIIa converted early deaths from exsanguination
      to late deaths from multiorgan failure.

PMID- 21944522
TI  - The impact of shave biopsy on the management of patients with thin melanomas.
AB  - Disagreement persists regarding the role that various biopsy methods should play
      in the diagnosis of primary cutaneous melanoma. We analyzed the indications for
      sentinel lymph node (SLN) biopsy and the rates of SLN involvement among biopsy
      techniques and deep margin status to attempt  to determine impact of shave biopsy
      on surgical management of patients with thin melanoma. All patients who underwent
      SLN biopsy for melanoma with Breslow thickness less than 1 mm between 1998 and
      2006 were identified. Patient and tumor characteristics were compared using
      chi(2)  tests for categorical variables. Continuous variables were reported as a
      mean +/- standard deviation and analyzed using t test. Of the 260 patients
      diagnosed with thin melanomas, 159 (61.2%) were diagnosed by shave biopsy; 101
      (38.8%) were diagnosed by other techniques. Of the  159 patients diagnosed by
      shave biopsy, 18.2 per cent (n = 29) underwent SLN biopsy with the only
      indication being positive deep margin. The frequency of SLN positivity did not
      differ between the biopsy groups (3.1% vs 4.0%, P = 0.726) or between groups that
      had positive or negative  deep margins (3.0% vs 3.3%, P = 0.839, respectively).
      For patients unable to undergo general anesthesia, the increased rate of
      performing SLN biopsy resulting from shave biopsy should limit its use in these
      patients. However, shave biopsy is a reasonable diagnostic method for  patients
      at low risk for general anesthesia, particularly because it results in comparably
      low rates of positive SLN. Thus each patient's unique clinical situation should
      be considered when deciding which biopsy technique is appropriate.

PMID- 21944523
TI  - Helicobacter pylori is not the predominant etiology for peptic ulcers requiring
      operation.
AB  - As the number of patients requiring operation for peptic ulcer disease (PUD)
      declines, presumed contemporary ulcer etiology has largely been derived from
      medically treated patients not subjected to surgery. The purpose of this study
      was to examine the specific causes of PUD in patients  requiring surgery. Our
      Acute Care Surgical Service registry was reviewed for patients operated on for
      complications of PUD from 2004 to 2009. Emphasis was placed on individual
      etiologic factors for PUD. There were 128 patients (52% male, 81% white) who
      underwent emergency operation including:  simple patch closure (n = 61, 48%);
      gastric resection (n = 22, 17%); gastric resection with vagotomy (n = 21, 16%);
      vagotomy and pyloroplasty (n = 18, 14%); or other procedures (n = 6, 5%).
      Complications necessitating operation were perforation (n = 79, 62%); bleeding (n
      = 29, 23%); obstruction  (n = 12, 9%); and intractability (n = 8, 6%).
      Perioperative mortality was 12.5 per cent. Risk factors for PUD included tobacco
      use (50%), alcohol abuse (34%), and steroids (21%). Nonsteroidal anti
      inflammatory use was confirmed in 68 (53%) patients. Of the 128 patients, 82
      (64%) were tested  for Helicobacter pylori, 33 (40%) of which were positive and
      49 (60%) negative. Helicobacter pylori, thus, was the confirmed ulcer etiology in
      only 26 per cent of cases. Unlike contemporary series of medically treated PUD,
      Helicobacter pylori may not be the predominant  etiologic factor in patients who
      experience complications requiring surgery. A "traditional" surgical approach
      with liberal use of vagotomy, not antibiotic triple therapy, may well be the
      preferred treatment consideration in such cases.

PMID- 21944524
TI  - Computerized tomography utilization in children with appendicitis-differences in
      referring and children's hospitals.
AB  - Increasingly, physicians rely on computerized tomography (CT) to aid in the
      workup of acute appendicitis (AA) in children despite the potential negative
      effects of CT-associated radiation exposure. Few studies have investigated the
      context or location in which the decision to perform  CT for AA is made. We
      sought to determine where the decision to use CT was made during the initial
      workup of pediatric patients who later underwent an appendectomy. We reviewed the
      medical record of all patients at a children's hospital (CH) receiving
      appendectomy over 10.5 years. We abstracted  clinical variables using an
      established clinical AA scoring system, demographics and outcome variables.
      Patients who underwent CT were compared with those who did not. Additionally, we
      identified the location where the CT was performed. Our children's hospital was
      compared with referring hospitals  (RHs) with regard to utilization of CT
      imaging. Five hundred and forty-six patients underwent appendectomy for AA at CH.
      Of these, 50 per cent underwent CT. Patients who initially presented at the RHs
      underwent CT at a significantly higher rate than those first presenting to CH (P
      <  0.0001). Moreover, we found that unlike at the RHs, patients with a higher AA
      score underwent CT at CH less often (P < 0.0002). RHs used CT more often than CH
      to diagnose AA in our cohort. CH avoided CT for patients with higher Alvarado
      scores. Further research is needed to elucidate  factors that lead healthcare
      providers to use CT for children with suspected AA to eliminate unnecessary CT
      associated radiation exposure.

PMID- 21944525
TI  - Blunt breast trauma: is there a standard of care?
AB  - The incidence of female blunt breast trauma (FBBT) is unknown, and there are no
      established treatment guidelines. The purpose of this study was to establish the
      incidence of FBBT, define associated injuries, and develop a treatment algorithm.
      This is a retrospective analysis of FBBT  at a Level I trauma center from October
      2000 through December 2008. The incidence, mechanism, and severity of injury,
      associated injuries, therapeutic interventions, and clinical outcomes were
      evaluated. A total of 14,499 patients were evaluated. Of these, 13,637 were blunt
      trauma victims  and 5,305 were female blunt trauma victims. One hundred and eight
      (2%) were diagnosed with FBBT. Although the average injury severity score (ISS)
      was 12.3 for all FBBT patients, 60 per cent of patients had an ISS > 15. Ninety
      four per cent were caused by motor vehicle crashes, with the  most common
      injuries being long bone fractures (45%) and rib fractures (44%). One hundred and
      one (93.5%) of the injuries were simple hematomas managed expectantly; seven
      patients (6.5%) had expanding hematomas with radiological evidence of active
      bleeding that ultimately required invasive  procedures, with six of them
      undergoing arteriogram and four successfully embolized. One patient was taken
      directly to the operating room for surgical ligation of a bleeding vessel. These
      data represent the largest series of breast injuries ever reported. Because FBBT
      is a marker for severe  associated injuries, our treatment algorithm recommends
      that women with radiological evidence of active bleeding who are hemodynamically
      stable be evaluated with a chest arteriogram plus or minus embolization. However,
      unstable patients with no other source of hemorrhage should undergo definitive 
      urgent operative repair. All other patients should be managed expectantly.

PMID- 21944526
TI  - Denver peritoneovenous shunts for the management of malignant ascites: a review
      of the literature in the post LeVeen Era.
AB  - Most case series describing peritoneovenous (PV) shunts for malignant ascites
      include both LeVeen and Denver shunts. Conclusions based on these studies are no
      longer clinically relevant since the LeVeen shunt has been discontinued. The
      purpose of this study was to identify outcomes  specific to Denver shunts to
      establish expected results in the modern era. Case series describing PV shunts
      for malignant ascites between 1980 and 2008 were identified through a keyword
      PUBMED search. Whenever possible, results attributable to Denver shunts were
      abstracted and analyzed. Nineteen  series describing 341 patients undergoing 353
      Denver PV shunts for malignant ascites were identified. The primary indications
      for PV shunts were unspecified or cancers of unknown origin (40%), ovarian cancer
      (16%), and pancreatic cancer (8%). Primary patency averaged 87 +/- 57 days.
      Seventy-four  per cent of patients died with functioning shunts. Complications
      occurred in 38% of patients including occlusion (24%) and disseminated
      intravascular coagulation (9%). Average survival of all patients was 3.0 +/- 1.7
      months and shunts provided effective palliation in 75.3%. One and a  half per
      cent of 133 patients who had autopsies were reported to have hematologic
      dissemination. These results are not statistically different than overall results
      reported for both shunts combined or LeVeen shunts alone. Studies that report
      combined outcomes with Denver and LeVeen shunts  for malignant ascites are
      neither negatively, nor positively influenced by one specific shunt. Expectations
      following PV shunting for malignant ascites do not have to be revised because
      LeVeen shunts are no longer available.

PMID- 21944527
TI  - Pencils and pens: an under-recognized source of penetrating injuries in children.
AB  - Unlike other sharp objects, pens and pencils are readily available to children
      both at home and school. Although case reports are published, no series of pen or
      pencil injuries have been reported in the recent literature. We therefore
      reviewed the incidence and injury profiles of writing  instruments as compared
      with other sources of penetrating trauma. The trauma registry from a large urban
      pediatric hospital system was queried for nonmissile, nonbite penetrating
      injuries from 2005 through 2009. Retrospective data was collected on
      demographics, injuries, operations, admissions,  and mortalities. Additionally,
      data regarding pen and pencil injuries from 2009 to 2010 were collected
      prospectively, and one case from 2003 was included retrospectively. Fourteen
      injuries from writing instruments were seen and involved the head and neck (9),
      chest (1), bladder/perineum (2),  and extremities (2). Eleven children were
      admitted and eight required surgical intervention. One child died from a
      transhemispheric brain injury after intraorbital penetration by a pencil.
      Penetrating trauma from writing instruments is not an uncommon source of injury
      and often requires surgical  intervention to remove the object. Injuries from
      pens and pencils can be severe or even fatal. Appropriate parent and teacher
      education regarding the potential risks may help to prevent such injuries.

PMID- 21944528
TI  - Differential trends in racial preferences for cosmetic surgery procedures.
AB  - There appears to be an increasing acceptance of cosmetic surgery procedures among
      minority populations in America. Our objective was to determine trends in
      elective cosmetic procedure utilization as they apply to racial/ethnic
      differences. A retrospective analysis was performed using  the Nationwide
      Inpatient Sample. Adult patients undergoing elective cosmetic procedures defined
      by the appropriate International Classification of Disease 9 Clinical
      Modification procedure codes were included. Demographic characteristics and
      hospital course particulars were evaluated. There  were 71,775 patients meeting
      the inclusion criteria. Median age was 48 years. The majority were female (90%),
      and white (65%). The median household income for the patient's zip code was most
      commonly in the highest economic quartile (4th quartile, 40%). The most common
      cosmetic procedure was  liposuction (67%). The overall mean percentage change in
      the frequency of these procedures showed a 1.8 per cent decline among white
      patients, whereas Black, Hispanic, Asian, and Native American patients had an
      increase of 7.5 per cent, 4.7 per cent, 14.5 per cent, and 105.5 per cent,
      respectively.  We conclude that there is an identified increasing trend in the
      proportion of racial/ethnic minorities represented among the recipients of
      cosmetic surgery procedures.

PMID- 21944529
TI  - Utilization of interventional radiology in the postoperative management of
      patients after surgery for locally advanced and recurrent rectal cancer.
AB  - The surgical management of locally advanced primary rectal cancer and locally
      recurrent rectal cancer requires complex operations frequently resulting in
      complicated postoperative courses. We sought to evaluate the utilization of
      interventional radiologic (IR) procedures in the management  of postoperative
      complications. Under Institutional Review Board approval, a prospective database
      of colorectal cancer patients undergoing resection from July 1999 to January 2010
      was analyzed. Data collected included demographics, operative procedure,
      complications, length of stay, and IR  utilization. Fisher's exact tests and
      logistic regression explored associations with necessitating an IR procedure
      during the postoperative period. Continuous variables were analyzed using
      Wilcoxon rank sum tests. One hundred and one patients underwent surgery and 66
      received intraoperative  electron radiotherapy (IOERT). Primary procedures
      included pelvic exenteration (n = 35), abdominoperineal resection (n = 25), low
      anterior resection (n = 23), paraaortic node dissection (n = 7), resection of
      isolated pelvic/retroperitoneal tumor (n = 7), and colectomy (n = 4). Sixty-two
      patients  required multivisceral resection including partial/total cystectomy (n
      = 30), small bowel resection (n = 25), oophorectomy (n = 15), vaginectomy (n =
      12), hysterectomy (n = 12), hepatectomy (n = 3), and nephrectomy (n = 3).
      Seventeen partial sacral resections and 47 pelvic sidewall resections  were also
      required. One hundred and thirty-eight complications were identified in 72
      patients, 30 of which required a procedural intervention. Twenty-seven IR
      procedures were performed including drainage of fluid collections (n = 14),
      nephrostomy tube placement (n = 8), arterial embolization  (n = 2), inferior vena
      cava filter placement (n = 2), and pleural drainage (n = 1). Only three
      reoperations were required, none related to failure of IR procedures. There were
      no deaths. Estimated blood loss > 2000 mL (P = 0.002), IOERT (P = 0.03), and
      incomplete resection  (P = 0.02) were found to be associated with postoperative
      IR utilization. Surgery for locally advanced primary rectal cancer and locally
      recurrent rectal cancer is associated with significant morbidity but low
      mortality. IR procedures play a significant role in the postoperative management 
      of these patients and may decrease the need for reoperation.

PMID- 21944530
TI  - Dynamic ultrasound and treadling: novel approaches to assess and improve lower
      extremity circulation.
AB  - The purpose of this study was to evaluate the safety and efficacy of a novel
      treatment of peripheral vascular disease through treadling and to report a
      dynamic vascular ultrasound technique. After informed consent, 17 volunteers were
      enrolled in the study. Ultrasound was used to measure  venous and arterial
      waveforms at the superficial femoral artery and vein in the subject's right thigh
      during a 5-minute baseline evaluation (resting), a 10-minute treadling period,
      and a 5-minute cool down period. Comparisons between flow velocities were made
      during the three trial periods  using a Repeated Measures Mixed Linear Model test
      with P < 0.05 considered significant. Twenty-six examinations were performed on
      subjects with an average age of 37 years (range, 25-75 years). Significant
      increases in maximum and minimum arterial and venous flow velocities  during the
      treadling time compared with the resting and cool down period were observed (P <
      0.0001) with no change in the subjects' vital signs. We found no significant
      difference in maximum and minimum arterial and venous flow velocities between the
      resting and cool down period  (P > 0.05). There were no untoward side effects,
      and all subjects were able to complete the protocol. Low-resistance treadling is
      safe and improves venous and arterial flow. Dynamic peripheral ultrasonography is
      a viable technique to assess flow during treadling. Potential future 
      implications of this study include the evaluation, treatment, and management of
      lower extremity vascular and chronic diseases and more sensitive peripheral
      vascular sonography through dynamic ultrasound.

PMID- 21944531
TI  - The bariatric surgery resident training experience: results of a national
      resident survey.

PMID- 21944532
TI  - Laparoscopic reoperative choledocholithotomy in elderly patients with prior
      complicated abdominal operations.

PMID- 21944533
TI  - Occult pulmonary arteriovenous malformation resulting in acute mesenteric
      ischemia and post-operative respiratory failure.

PMID- 21944535
TI  - Combined laparoscopic-endoscopic "Rendez-vous" procedure for minimally invasive
      resection of gastrointestinal stromal tumors of the stomach.

PMID- 21944534
TI  - Traumatic pulmonary pseudocyst: a rare but noteworthy entity.

PMID- 21944536
TI  - Surgery after neoadjuvant chemotherapy for locally advanced extrapulmonary poorly
      differentiated neuroendocrine cancer.

PMID- 21944537
TI  - Concerns for central line risks leads to admixture risks in parenteral nutrition
      administration.

PMID- 21944538
TI  - A novel frontier method of treating scalping injuries.

PMID- 21944539
TI  - Complete rupture of the inferior thyroid artery.

PMID- 21944540
TI  - Association study and expression analysis of porcine ESR1 as a candidate gene for
      boar fertility and sperm quality.
AB  - Male fertility is impaired through the lack of ESR1 (Estrogen Receptor 1) but
      little is known about the ESR1 roles in boar spermatogenesis and fertility.
      Therefore, this research was aimed at investigating the association with sperm
      quality and boar fertility traits in a total of 300 boars both from purebred
      Pietrain and Pietrain * Hampshire crosses. A SNP in coding region of ESR1g.672C>T
      in exon 1 was associated with sperm motility (P<0.05) and plasma droplet rate
      (P<0.01) while the polymorphism in non-coding region of ESR1g.35756T>C in inton 1
      was associated with non-return rate (P<0.05). Furthermore, to analyse the mRNA
      and protein expression of ESR1 in boar reproductive tissues, a total of six boars
      were divided into two groups [Group I (G-I) and Group II (G-II)], where G-I had
      relatively better sperm quality. ESR1 expression was higher in tissues collected
      from G-I boars than those of collected from G-II boars, and the difference in
      mRNA expression was significant (P<0.01) in head of epididymis. The ESR1 protein
      expression results from western blot coincided with the results of qRT-PCR. The
      ESR1 protein localization observed a strong staining in the cytoplasm of Sertoli
      cell in the testis, in the epithelial cells in head and tail of epididymis, in
      smooth muscle in tail of epididymis, and in the post acrosomal region and tail of
      the spermatozoa. These results will improve the understanding of the functions of
      the ESR1 in spermatogenesis within the reproductive tract and will shed light on
      ESR1 as a candidate in the selection of boar with good sperm quality and
      fertility.

PMID- 21944541
TI  - Pulses of prolactin before, during, and after luteolysis and synchrony with
      pulses of a metabolite of prostaglandin F2alpha in heifers.
AB  - Pulses of prolactin (PRL) and a metabolite of prostaglandin F2alpha (PGFM) were
      determined from hourly blood samples collected before, during, and after
      luteolysis (n=7 heifers). Progesterone concentrations were used to partition the
      results into six 12-h sets from 12h before to 36h after luteolysis. Pulses of PRL
      with a nadir-to-nadir interval of 4.4+/-0.2h were detected in each 12-h set.
      Pulses were rhythmic (P<0.05) in six heifers, beginning 12h before the end of
      luteolysis. The peak of a PRL pulse was greater (P<0.05) for the 12h after the
      end of luteolysis than for other 12-h sets, except for the last set of
      luteolysis. Area under the curve of a pulse was greater (P<0.05) for the 24h that
      encompassed the end of luteolysis than for two previous 12-h sets. Synchrony
      between the peaks of PRL and PGFM pulses was greater (P<0.03) during and after
      luteolysis (same hour for 29/39 pairs) than before luteolysis (0/12).
      Concentration of PRL centralized to the peak (Hour 0) of PGFM pulses was greater
      (P<0.05) at Hours 0 and 1 than at Hours -2, -1, and 3. Results supported the
      hypothesis that PRL is secreted in pulses in heifers. The pulses were most
      prominent and rhythmic during the last 12h of luteolysis and thereafter. The
      pulse peaks of PRL and PGFM were synchronized for most PRL pulses during and
      after luteolysis.

PMID- 21944542
TI  - Uncontrolled study assessing the impact of a psyllium-enriched extruded dry diet
      on faecal consistency in cats with constipation.
AB  - Two field trials, involving 66 cats (15 trial 1; 51 trial 2) were conducted to
      assess the efficacy of a psyllium-enriched diet for management of constipation in
      cats. After investigations and faecal evacuation (by enema if required), all cats
      were fed on a moderate fibre, psyllium-enriched, dry extruded diet. Additional
      therapy was either not used (trial 1), or initially allowed but was subsequently
      withdrawn if possible (trial 2). The diet was well tolerated, and palatability
      was excellent. Most cases improved after initial therapy (at 2 months; trial 1:
      14/15 [93%]; trial 2: 42/51 [82%]), and faecal consistency improved significantly
      in both trials (P < 0.001). Use of cisapride and lactulose decreased
      significantly in trial 2 (P < 0.001 for both). The diets used in these pilot
      studies were efficient in the management of recurrent feline constipation.
      Randomised control trials are now recommended to examine whether a clinical
      benefit can be proven.

PMID- 21944543
TI  - Detection of HCG-antigen based on enhanced photoluminescence of hierarchical ZnO
      arrays.
AB  - Specific antibody of Human chorionic gonadotrophin (HCG) was conjugated onto
      hierarchical ZnO arrays through the carbodiimide technique, and the
      photoluminescence (PL) intensity of ZnO arrays were enhanced linearly with the
      linked antibody concentration in the range of 40-160 ng/mL, which resulted from
      the nano sheet structure and rough surface in hierarchical ZnO columns. After the
      specific combination between antigen and antibody on hierarchical ZnO arrays, the
      enhanced PL intensity of ZnO arrays was also basically linear with the
      concentration of HCG antigen. Thus, detection of HCG antigen in the range of 2-20
      ng/mL was achieved based on PL intensity enhancement, suggesting that the
      prepared ZnO arrays are envisioned to be applied in the detection of early tumor
      markers in future.

PMID- 21944544
TI  - A colorimetric assay of protein kinase activity based on peptide-induced
      coagulation of gold nanorods.
AB  - We succeeded in applying gold nanorods (NRs) for the detection of protein kinase
      (PK) activity based on a substrate-induced coagulation mechanism. Because NRs
      have cationic surface charges due to surface-adsorbed cetyltrimethylammonium
      bromide, phosphorylated substrate peptides, which gain augmented anionic charges
      by phosphorylation, induce coagulation of the NRs, resulting in a red-to-blue
      color change of the corresponding NR dispersion. A large absorption coefficient
      of the NRs at the near-IR region enabled clear-cut detection of the peptide
      induced coagulation. IC(50) values of several inhibitors of c-Src determined by
      the present assay are consistent with reported values.

PMID- 21944545
TI  - Distribution, magnitude and characterization of the toxicity of Ukrainian
      estuarine sediments.
AB  - During the Soviet era, Ukraine was an important industrial and agricultural
      region of the Soviet Union. This industrial and agricultural activity resulted in
      contamination of Ukraine's estuaries with legacy anthropogenic pollutants.
      Investigations on the toxicological effects of this estuarine contamination have
      been limited. For this research, we measured the toxicity of contaminated
      sediments from four Ukrainian estuaries to several aquatic organisms over 3
      years. Sediment chemical analyses and whole sediment toxicity identification
      evaluations (TIEs) were also performed to determine the classes of contaminants
      contributing to toxicity. Toxic sediments were observed in several of the
      Ukrainian estuaries and chemical analyses of the sediments demonstrated
      anthropogenic contaminants were widely distributed. Contaminants were also
      detected in macrobenthic organisms collected from the sediments. Several lines of
      evidence, including TIEs, indicated hydrophobic organic chemicals (HOCs) were
      contributing substantially to observed toxicity. This information can guide
      environmental managers to prioritize portions of the estuaries requiring
      remediation.

PMID- 21944546
TI  - Design, synthesis, biophysical and biological studies of trisubstituted
      naphthalimides as G-quadruplex ligands.
AB  - A series of trisubstituted naphthalimides have been synthesized and evaluated as
      telomeric G-quadruplex ligands by biophysical methods. Affinity for telomeric G
      quadruplex AGGG(TTAGGG)(3) binding was first screened by fluorescence titrations.
      Subsequently, the interaction of the telomeric G-quadruplex with compounds
      showing the best affinity has been studied by isothermal titration calorimetry
      and UV-melting experiments. The two best compounds of the series tightly bind the
      telomeric quadruplex with a 2:1 drug/DNA stoichiometry. These derivatives have
      been further evaluated for their ability to inhibit telomerase by a TRAP assay
      and their pharmacological properties by treating melanoma (M14) and human lung
      cancer (A549) cell lines with increasing drug concentrations. A dose-dependent
      inhibition of cell proliferation was observed for all cellular lines during short
      term treatment.

PMID- 21944548
TI  - A study on the influence of ethanol over the primary cultured rat cortical
      neurons by using the scanning electron microscopy.
AB  - As an inhibitor and toxic factor of central nervous system, ethanol inhibits the
      action of the neurons and causes various kinds of neuronal damage. However, the
      precise mechanisms that ethanol-induced neuronal damage in the central nervous
      system remain unclear. In spite of thousands of published studies, little
      information is available on the neurons' morphological alteration in the central
      nervous system. In this study, we investigated the morphological alterations of
      the primary cultured rat cortical neurons after they were treated by different
      concentrations of ethanol using the scanning electron microscopy. Our results
      showed that the moderate or high concentration of ethanol could lead to
      morphological changes of these cultured rat cortical neurons, and they were
      closely associated with the duration of time. Our study will provide a new base
      for further studies on the effects of ethanol in the central nervous system.

PMID- 21944547
TI  - Directed evolution of a pyruvate aldolase to recognize a long chain acyl
      substrate.
AB  - The use of biological catalysts for industrial scale synthetic chemistry is
      highly attractive, given their cost effectiveness, high specificity that obviates
      the need for protecting group chemistry, and the environmentally benign nature of
      enzymatic procedures. Here we evolve the naturally occurring 2-keto-3-deoxy-6
      phosphogluconate (KDPG) aldolases from Thermatoga maritima and Escherichia coli,
      into enzymes that recognize a nonfunctionalized electrophilic substrate, 2-keto-4
      hydroxyoctonoate (KHO). Using an in vivo selection based on pyruvate auxotrophy,
      mutations were identified that lower the K(M) value up to 100-fold in E. coli
      KDPG aldolase, and that enhance the efficiency of retro-aldol cleavage of KHO by
      increasing the value of k(cat)/K(M) up to 25-fold in T. maritima KDPG aldolase.
      These data indicate that numerous mutations distal from the active site
      contribute to enhanced 'uniform binding' of the substrates, which is the first
      step in the evolution of novel catalytic activity.

PMID- 21944549
TI  - Infrapopulations of Procamallanus elatensis Fusco & Overstreet, 1979 (Nematoda:
      Camallanidae) in the rabbitfish Siganus rivulatus (Teleostei, Siganidae) from the
      Saudi coast of the Red Sea.
AB  - Factors regulating gastrointestinal nematode infrapopulations are to a great
      extent density-dependent. Here, 23 natural infrapopulations (41-281 individuals)
      of the viviparous nematode Procamallanus elatensis (Camallanidae) from the fish
      Siganus rivulatus were found distributed in a well-defined fundamental niche
      (posterior 55% of the intestine). Immature worms were mostly found in the
      anterior third of this niche, while mature worms were found in aggregations
      posterior to them and followed by gravid females in the posterior 20% of the
      intestine. This distribution strongly suggests that worms migrate towards the
      posterior intestine while they mature, copulate and reproduce. In small
      infrapopulations, the sex ratios were distinctly female-biased and the number of
      gravid females was low. In large infrapopulations, the sex ratios were distinctly
      male-biased and the number of gravid females was high. However, the mean lengths
      of both immature males and females and mature females decreased dramatically as
      the infrapopulation size increased, while those of mature males increased
      significantly. These results strongly suggest intraspecific competition and
      density-dependent regulation of mean worm length, and the increase in the mean
      length of mature males strongly suggests intense sexual selection and competition
      between mature males. Production of larvae by female worms decreased
      significantly as the infrapopulation size increased, suggesting a density
      dependent reduction in female worm fertility. The results are statistically
      significant and strongly suggest that infrapopulation self-regulation is through
      density-dependent mechanisms, in which development of immature worms,
      infrapopulation size, sex ratio, sexual selection and carrying capacity of the
      fundamental niche play essential roles in shaping and regulating the
      infrapopulations.

PMID- 21944550
TI  - Platforms for enrichment of phosphorylated proteins and peptides in proteomics.
AB  - Protein phosphorylation is a complex and highly dynamic process involved in
      numerous biological events. Abnormal phosphorylation is one of the underlying
      mechanisms for the development of cancer and metabolic disorders. The
      identification and absolute quantification of specific phospho-signatures can
      help elucidate protein functions in signaling pathways and facilitate the
      development of new and personalized diagnostic and therapeutic tools. This review
      presents a variety of strategies currently utilized for the enrichment of
      phosphorylated proteins and peptides before mass spectrometry analysis during
      proteomic studies. The investigation of specific affinity reagents, allied to the
      integration of different enrichment processes, is triggering the development of
      more selective, rapid and cost-effective high-throughput automated platforms.

PMID- 21944551
TI  - Activity-based protein profiling of host-virus interactions.
AB  - Virologists have benefited from large-scale profiling methods to discover new
      host-virus interactions and to learn about the mechanisms of pathogenesis. One
      such technique, referred to as activity-based protein profiling (ABPP), uses
      active site-directed probes to monitor the functional state of enzymes, taking
      into account post-translational interactions and modifications. ABPP gives
      insight into the catalytic activity of enzyme families that does not necessarily
      correlate with protein abundance. ABPP has been used to investigate several
      viruses and their interactions with their hosts. Differential enzymatic activity
      induced by viruses has been monitored using ABPP. In this review, we present
      recent advances and trends involving the use of ABPP methods in understanding
      host-virus interactions and in identifying novel targets for diagnostic and
      therapeutic applications.

PMID- 21944553
TI  - A note from the editors: Chagas disease: neglected in Europe?

PMID- 21944552
TI  - Economic evaluation research in the context of Child Welfare policy: a structured
      literature review and recommendations.
AB  - OBJECTIVES: With over 1 million children served by the US Child Welfare system at
      a cost of $20 billion annually, this study examines the economic evaluation
      literature on interventions to improve outcomes for children at risk for and
      currently involved with the system, identifies areas where additional research is
      needed, and discusses the use of decision-analytic modeling to advance Child
      Welfare policy and practice. METHODS: The review included 19 repositories of peer
      reviewed and non-peer-reviewed "gray" literatures, including items in English
      published before November, 2009. Original research articles were included if they
      evaluated interventions based on costs and outcomes. Review articles were
      included to assess the relevance of these techniques over time and to highlight
      the increasing discussion of methods needed to undertake such research. Items
      were categorized by their focus on: interventions for the US Child Welfare
      system; primary prevention of entry into the system; and use of models to make
      long-term projections of costs and outcomes. RESULTS: Searches identified 2,640
      articles, with 49 ultimately included (19 reviews and 30 original research
      articles). Between 1988 and 2009, reviews consistently advocated economic
      evaluation and increasingly provided methodological guidance. 21 of the original
      research articles focused on Child Welfare, while 9 focused on child mental
      health. Of the 21 Child Welfare articles, 81% (17) focused on the US system. 47%
      (8/17) focused exclusively on primary prevention, though 83% of the US system,
      peer-reviewed articles focused exclusively on prevention (5/6). 9 of the 17
      articles included empirical follow-up (mean sample size: 264 individuals; mean
      follow-up: 3.8 years). 10 of the 17 articles used modeling to project longer-term
      outcomes, but 80% of the articles using modeling were not peer-reviewed. Although
      60% of modeling studies included interventions for children in the system, all
      peer-reviewed modeling articles focused on prevention. CONCLUSIONS:
      Methodological guidance for economic evaluations in Child Welfare is increasingly
      available. Such analyses are feasible given the availability of nationally
      representative data on children involved with Child Welfare and evidence-based
      interventions. PRACTICE IMPLICATIONS: Policy analyses considering the long-term
      costs and effects of interventions to improve Child Welfare outcomes are scarce,
      feasible, and urgently needed.

PMID- 21944554
TI  - Chagas disease in Italy: breaking an epidemiological silence.
AB  - Chagas disease, a neglected tropical disease that due to population movements is
      no longer limited to Latin America, threatens a wide spectrum of
      people(travellers, migrants, blood or organ recipients,newborns, adoptees) also
      in non-endemic countries where it is generally underdiagnosed. In Italy, the
      available epidemiological data about Chagas disease have been very limited up to
      now, although the country is second in Europe only to Spain in the number of
      residents from Latin American. Among 867 at-risk subjectsscreened between 1998
      and 2010, the Centre for Tropical Diseases in Negrar (Verona) and the Infectious
      and Tropical Diseases Unit, University of Florence found 4.2% patients with
      positive serology for Chagas disease (83.4% of them migrants, 13.8% adoptees).No
      cases of Chagas disease were identified in blood donors or HIV-positive patients
      of Latin American origin. Among 214 Latin American pregnant women,three were
      infected (resulting in abortion in one case).In 2005 a case of acute Chagas
      disease was recorded in an Italian traveller. Based on our observations, we
      believe that a wider assessment of the epidemiological situation is urgently
      required in our country and public health measures preventing transmission and
      improving access to diagnosis and treatment should be implemented.

PMID- 21944555
TI  - Chagas disease in Switzerland: history and challenges.
AB  - Chagas disease, endemic in Latin America, is an emerging health problem in Europe
      affecting an estimated 80,000 persons. Around 60,000 Latin American migrants live
      in Switzerland, and cases of Chagas disease have been reported since 1979. As of
      June 2011, 258 cases have been diagnosed, mostly adults in the indeterminate
      phase of the chronic stage of the disease. Vertical transmission has been
      identified and there is a high potential for blood- and organ-borne transmission
      in the absence of systematic screening. Major challenges include (i) raising
      awareness among migrants and healthcare professionals, (ii) developing national
      protocols for screening and treatment targeting high-risk groups such as pregnant
      woman, newborns, migrants from highly endemic areas (e.g. Bolivia), and
      immunocompromised migrants, (iii) preventing blood- and organ-borne transmission
      by appropriate screening strategies, (iv) taking into account the social
      vulnerability of individuals at risk in the design and implementation of public
      health programmes, and (v) facilitating contacts with the communities at risk
      through outreach programmes, for example in churches and cultural groups.

PMID- 21944556
TI  - Chagas disease in European countries: the challenge of a surveillance system.
AB  - A study of aggregate data collected from the literature and official sources was
      undertaken to estimate expected and observed prevalence of Trypanosoma cruzi
      infection, annual incidence of congenital transmission and rate of underdiagnosis
      of Chagas disease among Latin American migrants in the nine European countries
      with the highest prevalence of Chagas disease. Formal and informal data sources
      were used to estimate the population from endemic countries resident in Europe in
      2009, diagnosed cases of Chagas disease and births from mothers originating from
      endemic countries. By 2009, 4,290 cases had been diagnosed in Europe, compared
      with an estimated 68,000 to 122,000 expected cases. The expected prevalence was
      very high in undocumented migrants (on average 45% of total expected cases) while
      the observed prevalence rate was 1.3 cases per 1,000 resident migrants from
      endemic countries. An estimated 20 to 183 babies with congenital Chagas disease
      are born annually in the study countries. The annual incidence rate of congenital
      transmission per 1,000 pregnancies in women from endemic countries was between
      none and three cases. The index of under diagnosis of T. cruzi infection was
      between 94% and 96%. Chagas disease is a public health challenge in the studied
      European countries. Urgent measures need to be taken to detect new cases of
      congenital transmission and take care of the existing cases with a focus on
      migrants without legal residency permit and potential difficulty accessing care.

PMID- 21944557
TI  - EuroTravNet: imported Chagas disease in nine European countries, 2008 to 2009.
AB  - In recent years, Chagas disease has emerged as a disease of importance outside of
      endemic areas, largely as a result of migration. In Europe, clinicians may have
      to treat infected migrants from endemic areas as well as people with acute
      infections transmitted congenitally,through organ donation or blood
      transfusion.We describe here the characteristics of patients diagnosed with
      chronic Chagas disease at the core clinical sites of the EuroTravNet network
      during 2008 and 2009. Of the 13,349 people who attended the sites, 124 had
      chronic Chagas disease. Most (96%) were born in Bolivia and the median number of
      months in the country of residence before visiting a EuroTravNet core site was 38
      months (quartile (Q1)-Q3: 26-55). The median age of the patients was 35 years (Q1
      Q3: 29-45) and 65% were female. All but one were seen as outpatients and the most
      frequent reason for consultation was routine screening. Considering that Chagas
      disease can be transmitted outside endemic regions and that there is effective
      treatment for some stages of the infection, all migrants from Latin America
      (excluding the Caribbean) should be questioned about past exposure to the
      parasite and should undergo serological testing if infection is suspected.

PMID- 21944558
TI  - Chagas disease at the crossroad of international migration and public health
      policies: why a national screening might not be enough.
AB  - Since the year 2000, Chagas disease, traditionally known as a rural Latin
      American affliction, has been rising in the ranking of international health
      priorities due to the growing migration flows from endemic areas to non-endemic
      ones. Using the example of Italy and reporting preliminary results of a study
      carried out in the district of Bologna, the paper will argue that a disease
      centred public health approach might be inadequate when dealing with complex and
      uncertain situations, in which complete statistical data are not available or not
      reliable, and in which the involved actors, health professionals on the one side,
      migrants on the other, appear to be unaware of the issue, or might even be
      denying it. In such a context, an effective public health approach should be
      capable of crossing disciplinary boundaries and bridging the gap between health
      services and communities, as well as between health and social issues.

PMID- 21944559
TI  - EUVAC-Net: the surveillance network for vaccine-preventable diseases is now
      hosted by ECDC.

PMID- 21944560
TI  - New WHO Europe action plan to fight MDR-TB.

PMID- 21944561
TI  - The role of adolescents' morality and identity in volunteering. Age and gender
      differences in a process model.
AB  - The aim of this study was to explain adolescents' volunteering in terms of their
      morality and identity and to examine the moderation effect of gender and age in
      this process. Data were collected among 698 Dutch adolescents aged 12 to 20 (M =
      15.19; SD = 1.43). Adolescents' moral reasoning was positively associated with
      understanding moral issues and thinking about public responsibility towards these
      issues. In turn, moral understanding, along with being personally committed to
      act upon moral issues, were positively associated with identity. Extending the
      number of identity contexts tended to be related to being more likely to
      volunteer and to more volunteering involvement. Adolescents' identity integration
      was not related to how likely they were to volunteer, and was negatively related
      to their volunteering involvement. Clearer effects were found when
      differentiating between adolescent gender and age groups. Future research could
      examine this process over time, along with additional factors that may further
      explain adolescents' volunteering, and examine their age and gender specific
      effects.

PMID- 21944562
TI  - Antibody binding to porcine sialoadhesin reduces phagocytic capacity without
      affecting other macrophage effector functions.
AB  - Sialoadhesin (Sn) is a macrophage-restricted endocytic receptor involved in cell
      cell, cell-matrix and cell-pathogen interactions. Recently, porcine Sn (pSn) was
      shown to be involved in signaling and lately Sn is gaining interest as a
      potential target for immunotherapy. However, little is known about the effect of
      ligand binding to Sn on macrophage effector functions. In this study, we tested
      the effect of antibody binding to pSn on macrophage viability, phagocytosis of
      microspheres, uptake and processing of soluble antigens, reactive oxygen/nitrogen
      species production, MHC I and MHC II cell surface expression and cytokine
      production. This was done by treatment of porcine primary alveolar macrophages
      with the pSn-specific mAb 41D3, or an isotype-matched control mAb. No significant
      effect on most effector functions under study was observed, except for a
      significant reduction of phagocytosis. Thus, antibody binding to pSn can
      downregulate phagocytosis, which could have implications on homeostasis,
      infectious and immune diseases, and immunotherapy.

PMID- 21944563
TI  - Mountain cedar pollen induces IgE-independent mast cell degranulation, IL-4
      production, and intracellular reactive oxygen species generation.
AB  - Cedar pollens cause severe allergic disease throughout the world. We have
      previously characterized allergenic pollen glycoproteins from mountain cedar
      (Juniperus ashei) that bind to allergen-specific immunoglobulin E (IgE). In the
      present report, we investigated an alternative pathway of mast cell activation by
      mountain cedar pollen extract through IgE-independent mechanisms. We show that
      mountain cedar pollen directly induces mast cell serotonin and IL-4 release and
      enhances release induced by IgE cross-linking. Concomitant with mediator release,
      high levels of intracellular reactive oxygen species (ROS) were generated, and
      both ROS and serotonin release were inhibited by anti-oxidants. These findings
      suggest that alternative mechanisms exist whereby pollen exposure enhances
      allergic inflammatory mediator release through mechanisms that involve ROS. These
      mechanisms have the potential for enhancing the allergenic potency of pollens.

PMID- 21944564
TI  - A comparative qualitative analysis of stories of spousal caregivers of people
      with dementia: negative, ambivalent, and positive experiences.
AB  - BACKGROUND: Caregivers of people with dementia describe a wide spectrum of
      caregiving experiences, from very negative to very positive. Previous research
      reveals that differences exist, but how or why the experiences differ has not
      been well addressed. OBJECTIVE: The purpose of this study was to explore how the
      experiences of spousal caregivers of people with dementia differ. METHODS: This
      study was a secondary analysis of interviews collected from a longitudinal
      caregiver skill training intervention for caregivers of those with degenerative
      diseases (parent study). For the purpose of this analysis, 57 interviews from 21
      spousal caregivers of people with dementia in the control group of the parent
      study were analyzed. The interviews from the parent study were collected at
      baseline, 6 months, and 12 months post-enrollment. RESULTS: Three groups of
      caregivers were identified based on how they described their experience; a
      negative group, an ambivalent group and a positive group. The negative group
      described both past and present relationships with their spouse in negative
      terms. These caregivers expressed no positives in caregiving. Their focus was on
      their own unmet needs rather than their spouses' needs. These caregivers reported
      significant caregiving burden. The ambivalent group reported that the
      relationship they had with the spouse was lost, but they still described
      satisfaction in being able to care for the spouse. They described mixed emotions
      about caregiving and had difficulty accepting that their partners could no longer
      reciprocate in the relationship. The positive group described both their past and
      present relationship with the care recipient in loving terms. They focused on
      aspects of the relationship they still had, rather than what had been lost. They
      expressed satisfaction with caregiving, were other-focused, and not highly
      burdened by caregiving. They understood that their partner could not reciprocate,
      and expected nothing in return. Descriptions of the positive group suggest target
      areas for caregiver interventions. CONCLUSION: Spousal caregivers of people with
      dementia can be encouraged toward more positive caregiving experiences through
      empathy-building interventions and enhanced understanding and acceptance of
      changes in the care recipient.

PMID- 21944565
TI  - Nurse-led central venous catheter insertion-procedural characteristics and
      outcomes of three intensive care based catheter placement services.
AB  - BACKGROUND: Nurse-led central venous catheter placement is an emerging clinical
      role internationally. Procedural characteristics and clinical outcomes is an
      important consideration in appraisal of such advanced nursing roles. OBJECTIVES:
      To review characteristics and outcomes of three nurse-led central venous catheter
      insertion services based in intensive care units in New South Wales, Australia.
      DESIGN: Using data from the Central Line Associated Bacteraemia project in New
      South Wales intensive care units. Descriptive statistical techniques were used to
      ascertain comparison rates and proportions. PARTICIPANTS: De-identified outcome
      data of patients who had a central venous catheter inserted as part of their
      therapy by one of the four advanced practice nurses working in three separate
      hospitals in New South Wales. RESULTS: Between March 2007 and June 2009, 760
      vascular access devices were placed by the three nurse-led central venous
      catheter placement services. Hospital A inserted 520 catheters; Hospital C with
      164; and Hospital B with 76. Over the study period, insertion outcomes were
      favourable with only 1 pneumothorax (1%), 1 arterial puncture (1%) and 1 CLAB
      (1%) being recorded across the three groups. The CLAB rate was lower in
      comparison to the aggregated CLAB data set [1.3 per 1000 catheters (95% CI=0.03
      7.3) vs. 7.2 per 1000 catheters (95% CI=5.9-8.7)]. CONCLUSION: This study has
      demonstrated safe patient outcomes with nurse led CVC insertion as compared with
      published data. Nurses who are formally trained and credentialed to insert CVCs
      can improve organisational efficiencies. This study adds to emerging data that
      developing clinical roles that focus on skills, procedural volume and competency
      can be a viable option in health care facilities.

PMID- 21944567
TI  - Comments regarding 'Endovascular stent-graft treatment for Stanford type A aortic
      dissection'.

PMID- 21944566
TI  - Prospective evaluation of bone mineral density among middle-aged HIV-infected and
      uninfected women: Association between methadone use and bone loss.
AB  - OBJECTIVE: We undertook a prospective study to assess the impact of HIV infection
      on BMD in a cohort of HIV-infected and uninfected women that included illicit
      drug users, and to measure the contribution of traditional risk factors as well
      as HIV-related factors to loss of BMD over time. METHODS: We analyzed BMD at
      baseline and after >=18 months in 245 middle-aged HIV-infected and 219 uninfected
      women, and conducted linear regression analysis to determine factors associated
      with annual BMD change at the femoral neck, total hip and lumbar spine. RESULTS:
      HIV-infected women had lower baseline BMD at the femoral neck and total hip
      compared with controls; unadjusted rates of BMD change did not differ by HIV
      status at any site. In multivariable analyses, we found that HIV seropositivity
      without protease inhibitor (PI) use was associated with BMD decline at the lumbar
      spine (-.009g/cm(2) per year, p=.03). Additional factors associated with BMD
      decline were: postmenopausal status, lower BMI, and methadone use at the lumbar
      spine; postmenopausal status and hepatitis C seropositivity at the femoral neck;
      and postmenopausal status, age, smoking, and lower BMI at the total hip (all
      p<.05). Among HIV-infected women, >=3 years of PI use was associated with an
      increase in lumbar spine BMD (.013g/cm(2) per year, p=.008). CONCLUSIONS: Bone
      loss among HIV-infected middle-aged women was modest, and possibly mitigated by
      PI use. Methadone use was associated with BMD decline, and should be considered
      when evaluating women for osteoporosis risk.

PMID- 21944568
TI  - Comments regarding 'Carotid endarterectomy within seven days after the
      neurological index event is safe and effective in stroke prevention'.

PMID- 21944569
TI  - Fine structure of translocation breakpoints within the major breakpoint region in
      BCR-ABL1-positive leukemias.
AB  - The chromosomal translocation t(9;22)(q34;q22), with expression of the BCR-ABL1
      fusion gene is the cytogenetic and molecular hallmark of chronic myeloid leukemia
      (CML) and a subset of acute lymphoblastic leukemia (ALL). Basically two types of
      BCR-ABL1 chimeric mRNA transcripts have been observed: (1) e13a2/e14a2
      transcripts in CML and ALL, resulting from chromosomal breaks in the major
      breakpoint cluster region (M-bcr) of the BCR gene and (2) e1a2 transcripts in ALL
      resulting from breaks in the minor breakpoint cluster region (m-bcr) of the BCR
      gene. To gain a better understanding of this molecular alteration, we developed a
      long-distance inverse PCR (LDI PCR) method for M-bcr breakpoint identification in
      BCR-ABL1-positive cases and were thus able to identify the chromosomal
      breakpoints within the M-bcr in 62 BCR-ABL1-positive samples. The corresponding
      reciprocal breakpoints were identified and molecularly characterized in 45 of
      these cases. In 2 samples, the breaks were located 5' to the ABL1 locus and in
      one case, the der(9) break was identified on 9q34.13 several hundred kB 3'
      telomeric to ABL1. The analysis of breaks revealed no significant clustering and
      no association with repetitive elements (Alu, L1, L2) or recombination signal
      sequence sites. The established LDI PCR permits fast, relatively easy and
      unbiased identification of breakpoints in the M-bcr region of BCR and also
      enables the molecular analysis of more complex translocations with breakpoints
      outside the ABL1 gene locus or other BCR fusion genes.

PMID- 21944570
TI  - Deciding to join a perinatal randomised controlled trial: experiences and views
      of pregnant women enroled in the Magpie Trial.
AB  - OBJECTIVE: to provide insight into pregnant women's experiences of participating
      in a large multi-centre randomised trial. DESIGN: qualitative semi-structured
      interviews. SETTING: six UK maternity units. PARTICIPANTS: women recruited to the
      Magpie Trial. The Magpie Trial was a trial of prophylactic anticonvulsants for
      women with severe pre-eclampsia. MEASUREMENTS FINDINGS: a number of major but
      related themes emerged regarding influences on the women's decision-making:
      unpredictability of pre-eclampsia; quality of information received; role of
      others in the decision-making process; perceived personal benefit from trial
      participation; and perception of voluntariness of joining. KEY CONCLUSIONS: the
      data presented give valuable insights into the women's views and experiences of
      decision-making. Research into many of the other elements of care given during
      pregnancy and childbirth is still needed, and with this need comes the ethical
      responsibility of researchers to ensure trials are performed in the most
      scientifically robust ways, which are also acceptable to women. To examine the
      experiences of those involved in trial participation and their views about doing
      so is a crucial way of advancing this. The QUOTE Study increases understanding of
      the experiences of women participating in a randomised controlled trial.
      IMPLICATIONS FOR PRACTICE: the general implication for practice is that
      procedures are needed that can improve the design and conduct of randomised
      trials and therefore ultimately enhance the experience for future women.
      Recommendations include informed consent should be tailored, recognising
      individual differences in the desire for information. For instance the time
      individuals need to make consent decisions varies, as do their desires to consult
      with family before agreeing.

PMID- 21944572
TI  - Becoming culturally sensitive: a painful process?
AB  - OBJECTIVE: to discuss how midwifery students develop cultural sensitivity.
      DESIGN: students carried out international observational elective placements and
      13 matched self-assessments from before and after a Global Midwifery Module were
      compared. The module is based around a model of immersion and permitted measured
      responses and qualitative evaluation to be explored. SETTINGS: observational
      placements occurred in the UK, America, Canada, and Gutamala. PARTICIPANTS:
      seventeen year 3 midwifery students. FINDINGS: raised awareness about
      international midwifery was identified; the module contributed to enhancement of
      practice, confidence about caring for those from a different culture varied, the
      process of critical reflection was uncomfortable for some. KEY CONCLUSIONS:
      critical reflection facilitated in a safe place may support individuals to
      transform their way of thinking. IMPLICATIONS FOR PRACTICE: responsibility for
      developing cultural sensitivity should lie with the individual. However, leaders
      need to facilitate space for critical reflection. Critical self-assessment and
      reflection about cultural sensitivity should be part of a life long learning
      approach.

PMID- 21944571
TI  - Effect of a peer support service on breast-feeding continuation in the UK: a
      randomised controlled trial.
AB  - OBJECTIVE: to assess the effectiveness of a peer support worker (PSW) service on
      breast-feeding continuation. DESIGN: cluster randomised controlled trial
      (ISRCTN16126175). SETTING: Primary Care Trust, UK serving a multi-ethnic, socio
      economically disadvantaged population. PARTICIPANTS: 2,724 women giving birth
      following antenatal care from 66 clinics: 33 clinics (1,267 women) randomised to
      the PSW service and 33 clinics (1,457 women) to usual care. 848 women consented
      to additional follow-up by questionnaire at 6 months. INTERVENTION: PSW service
      provided in the antenatal and postnatal period. MEASUREMENTS: any and exclusive
      breast feeding at 10-14 days obtained from routine computerised records and at 6
      weeks and 6 months from a questionnaire. FINDINGS: follow-up: 94% at 10-14 days,
      67.5% at 6 months. There was no difference in any breast feeding at 10-14 days
      between intervention and usual care, odds ratio (OR) 1.07 (95% CI 0.87-1.31,
      p=0.54). Proportion of women reporting any breast feeding in the intervention
      group at 6 weeks was 62.7% and 64.5% in the usual care group OR 0.93 (95% CI 0.64
      1.35); and at 6 months was 34.3% and 38.9%, respectively, OR 1.06 (95% CI 0.71
      1.58). KEY CONCLUSIONS: universal antenatal peer support and postnatal peer
      support for women who initiated breast feeding did not improve breast-feeding
      rates up to 6 months in this UK population. IMPLICATIONS FOR PRACTICE: with high
      levels of professional support part of usual maternity care it may not be
      possible for low intensity peer support to produce additional benefit. More
      intensive or targeted programmes might be effective, but should have concurrent
      high quality evaluation.

PMID- 21944573
TI  - Primary maternity care reform: whose influence is driving the change?
AB  - BACKGROUND: in 2009 the Australian government announced a programme of reform
      that will change the way maternity services have traditionally been delivered. A
      shift to a primary maternity care model has occurred despite strong challenges
      from medicine and a general public that has embraced high technology in all
      aspects of life including childbirth. AIM: a critical analysis was undertaken for
      the purpose of identifying discourses that have influenced the direction of the
      Australian maternity care reform agenda. METHOD: within a critical discourse
      analysis framework data were collected from state, territory and commonwealth
      government policy documents, and selected written submissions from national key
      stakeholder organisations to the National Review of Maternity Services 2008.
      FINDINGS: three discourses influencing the direction of the reform are described,
      these include the following: 'Australia is one of the safest place to give birth
      or to be born, but not for everyone'; 'maternity care is primarily about mothers
      and babies, not about the service or the health professionals' and 'government
      must ensure provision of safe and sustainable maternity services'. CONCLUSION:
      the Australian government has strong support for the primary maternity care
      reform backed by a strong key stakeholder alliance involving consumers, midwives
      and rural doctors. On the contrary to the position of the key stakeholder
      alliance, the obstetric position has been unable to provide government with
      solutions to escalating costs and workforce deficits in the delivery of safe and
      sustainable maternity services. Consumers, rural doctors, midwives and government
      all agree on the need to safeguard excellent safety and quality standards whilst
      at the same time reducing high levels of medical intervention and providing
      options for care in a reformed maternity service designed to meet the needs of
      all Australian women.

PMID- 21944574
TI  - Delay in seeking treatment by patients with stroke: who decides, where they go,
      and how long it takes.
AB  - OBJECTIVES: To find out about stroke patients: who decides to seek medical help,
      where they go, how long it takes to contact the health system and to arrive at
      the ED. METHODS: Prospective study of patients admitted in our hospital for
      transient or established stroke. RESULTS: Among 388 stroke patients (mean NIHSS
      of 7.8 (+/-7.4), there were 37 intracerebral hemorrhage, 70 TIA, and 281 cerebral
      infarction. 39.2% arrived at the ED in less than 3h. The decision to seek medical
      help was taken by patients in 20.4% of the episodes. First contact was with
      primary care in 48.3% of the cases and with Emergency Medical Services in 18.2%.
      The median time of decision was 60min [P25:15; P75:323]. Considering the event as
      serious, recognizing the stroke, not going to a primary care physician, having a
      TIA and onset away from home significantly decreased delay. Age, sex and previous
      stroke were not associated with less delay in decision nor with an earlier
      arrival to the ED. CONCLUSIONS: In order to improve stroke treatment it is
      necessary to harness the use of the 112 emergency line and include primary care
      in the stroke assistance chain.

PMID- 21944575
TI  - [Features information of the surgical process and patients' satisfaction].
AB  - AIM: To explore the relationship between the perceived characteristics of the
      information that patients receive on the surgical procedure and their
      satisfaction. METHOD: Observational cross-sectional study, conducted by the use
      of surveys at the Virgen Macarena University Hospital (VMUH) of Seville, in July
      2009. It involved 75 patients selected by convenience sampling. The ANOVA test
      was performed according to the assessed characteristics of the information in
      order to determine the differences in satisfaction. RESULTS: The value obtained
      in the satisfaction with the information of physicians and nurses are high.
      Nevertheless, 42, 5% had the impression of not being able to ask questions and
      71, 4% were not asked for authorized relatives to be informed. When applying the
      ANOVA test, statistically significant differences were obtained for the
      satisfaction with the information received by the physicians, depending on having
      received it prior to surgery, and the privacy while receiving this information.
      On the other hand, the satisfaction with the information provided by nursing
      professionals is related to the supplying of information on discharge and further
      home care instructions.

PMID- 21944576
TI  - [Gynecological emergencies: etiology and degree of gravity].
AB  - OBJECTIVE: To evaluate the type and the emergency degree of the pathologies met
      in gynecological emergencies. METHODS: prospective study including 205 patients
      presented to the Emergency department of a maternity level 3 between the 2011
      January 4 and February 15. RESULTS: One hundred and ninety-four patients (95%)
      came from their own initiative. One hundred and eighty-one patients (88%)
      consulted for abdominal/pelvic or lumbar pain and or metrorragia. The mean age of
      the patients was of 31 +/- 11 years and the average waiting time before being
      examined was of 84 +/- 101 minutes. For 94 patients (46%), the diagnosis was an
      asymptomatic intra-uterine pregnancy in 41 cases or associated with minor
      symptoms. 21 patients (8.9%) consulted for menstruation with or without
      dysmenorrhea, 17 (8,3%) had a miscarriage, 14 (7%) a genital infection, 11 (5%)
      an ovarian pathology and eight (4%) an ectopic pregnancy or its follow-up. Seven
      patients had an axillary lymphocele or a breast tumor and four symptomatic
      myomas. Six patients presented with non-gynecological pathologies. In 23 cases
      (11%) no organic cause was found. Only 24 patients (12%) were hospitalized and
      nine (4.5%) operated. CONCLUSION: Most of the patients consulted for minor
      obstetrical or gynecological pathologies without relation with the function of
      Emergency department. Ectopic pregnancy remains a rare event. Better information
      of the users on the significance of the urgency is desirable. Consultation of a
      referent physician before emergency services should be privileged.

PMID- 21944577
TI  - [Use of peak systolic velocity in the middle cerebral artery after serial
      intravenous fetal exchange transfusions in the end of pregnancy].
AB  - OBJECTIVES: Our aim was to assess the efficiency of the peak systolic velocity in
      the middle cerebral artery (PSV-MCA) to predict neonatal anemia at the end of
      pregnancies after serial intravenous fetal exchange transfusions (IFET) for red
      cell fetomaternal immunization. PATIENTS AND METHODS: We conducted a
      retrospective study from 01/01/2004 to 31/12/2009 of 25 pregnancies after IFET
      for red-cell fetomaternal immunization, in Saint Vincent de Paul Hospital, Paris.
      The study assessed correlation between the last prenatal PSV-MCA measured and
      hemoglobin concentration at birth and other neonatal data. RESULTS: Last prenatal
      PSV-MCA and hemoglobin concentration at birth were significantly correlated (r=
      0.39, P<0.01). CONCLUSION: There is a good correlation between last PSV-MCA
      measured before birth and neonatal haemoglobin and complexity of neonatal care
      linked to anemia. Cerebral Doppler is useful for the follow-up of pregnancies at
      risk for anemia even in the end of the pregnancy and after serial intravenous
      fetal exchange transfusions.

PMID- 21944578
TI  - [Preimplantation diagnosis with HLA typing: birth of the first double hope child
      in France].
AB  - Preimplantation genetic diagnosis (PGD) is authorized in France since 1999. After
      10 years, technical results are encouraging. With the development of new
      technologies, our team is able to diagnosis the large majority of chromosome
      translocations and 75 monogenic diseases. However, PGD remains limited because of
      the growing augmentation of demands causing an increasing delay for the first
      procedure of more than 18 months. Since 2006, 19 couples asked for a PGD with HLA
      typing. In January 2011, 11 couples have already been included in our PGD
      program. The birth of the first child after PGD with HLA typing offers new
      perspectives of treatment for these couples.

PMID- 21944580
TI  - Implementation Science for nursing: evidence needed!: call for papers for a
      special issue.

PMID- 21944579
TI  - Wnt antagonists bind through a short peptide to the first beta-propeller domain
      of LRP5/6.
AB  - The Wnt pathway inhibitors DKK1 and sclerostin (SOST) are important therapeutic
      targets in diseases involving bone loss or damage. It has been appreciated that
      Wnt coreceptors LRP5/6 are also important, as human missense mutations that
      result in bone overgrowth (bone mineral density, or BMD, mutations) cluster to
      the E1 propeller domain of LRP5. Here, we report a crystal structure of LRP6 E1
      bound to an antibody, revealing that the E1 domain is a peptide recognition
      module. Remarkably, the consensus E1 binding sequence is a close match to a
      conserved tripeptide motif present in all Wnt inhibitors that bind LRP5/6. We
      show that this motif is important for DKK1 and SOST binding to LRP6 and for
      inhibitory function, providing a detailed structural explanation for the effect
      of the BMD mutations.

PMID- 21944581
TI  - Fathers' sense of security during the first postnatal week--a qualitative
      interview study in Sweden.
AB  - BACKGROUND: father's sense of security in the early postnatal period is important
      for the whole family. An instrument, which measures Parents' Postnatal Sense of
      Security (the PPSS instrument), is under development. OBJECTIVE: to explore and
      describe factors, which influence fathers' sense of security during the first
      postnatal week. METHODS: an explorative design with a qualitative approach was
      used. Thirteen fathers from three hospital uptake areas in Southern Sweden were
      interviewed using focus group discussions and individual interviews. Analysis was
      carried out using qualitative content analysis. FINDINGS: participation in the
      processes of pregnancy birth and early parenthood emerged as the main category
      for fathers' postnatal sense of security. The emergent categories were;
      'willingness to participate and take responsibility', 'being given the
      opportunity to take responsibility', 'being assured about mother's and baby's
      well-being', 'having someone to turn to-knowing who to ask', 'being met as an
      individual' and 'being met by competent and supporting staff'. KEY CONCLUSIONS
      AND IMPLICATIONS FOR PRACTICE: new and specific items of importance when
      investigating fathers' sense of security during the early postnatal period have
      been pinpointed. Fathers' sense of early postnatal security may be enhanced by
      giving them a genuine opportunity to participate in the whole process and by
      giving them the opportunity to stay overnight at the hospital after the birth.
      Midwives and care organisations need to give clear information about where
      competent help and advice can be obtained at all hours. Midwives should
      strengthen the fathering role by acknowledging and listening to the father as an
      individual person.

PMID- 21944582
TI  - Perfluorocarbon emulsions prevent hypoxia of pancreatic beta-cells.
AB  - As oxygen carriers, perfluorocarbon emulsions might be useful to decrease hypoxia
      of pancreatic islets before transplantation. However, their hydrophobicity
      prevents their homogenisation in culture medium. To increase the surface of
      contact between islets and Perfluorooctyl bromide  (PFOB), and consequently
      oxygen delivery, we tested effect of a PFOB emulsion in culture medium on beta
      cell lines and rat pancreatic islets. RINm5F beta-cell line or pancreatic rat
      islets were incubated for 3 days in the presence of PFOB emulsion in media (3.5%
      w/v). Preoxygenation of  the medium was performed before culture. Cell viability
      was assessed by apoptotic markers (Bax and Bcl-2) and by staining (fluoresceine
      diacetate and propidium iodide). beta-Cell functionality was determined by
      insulin release during a glucose stimulation test and. Hypoxia markers, HIF
      1alpha  and VEGF, were studied at days 1 and 3 using RT-PCR, Western blotting,
      and ELISA. PFOB emulsions preserved viability and functionality of RINm5F cells
      with a decrease of HIF-1alpha and VEGF expression. Islets viability was preserved
      during 3 days of culture. Secretion of VEGF was higher  in untreated control
      (0.09 +/- 0.041 MUg VEGF/mg total protein) than in PFOB emulsion incubated islets
      (0.02 +/- 0.19 MUg VEGF/mg total protein, n = 4, p < 0.05) at day 1. At day 3,
      VEGF secretion was increased as compared to day 1 in control (0.23 +/- 0.04  MUg
      VEGF/mg total protein) but it was imbalance by the presence of PFOB emulsion
      (0.09 +/- 0.03 MUg VEGF/mg total protein, n = 5, p < 0.05). While insulin
      secretion was maintained in response to a glucose stimulation test until day 3
      when islets were incubated in  the presence of PFOB emulsion preoxygenated (0.81
      +/- 0.16 at day 1 vs. 0.75 +/- 0.24 at day 3), the ability to secrete insulin in
      the presence of high glucose concentration was lost in islets controls (0.51 +/-
      0.18 at day 1 vs. 0.21 +/- 0.13 at day 3). Atmospheric oxygen  delivery by PFOB
      emulsion might be sufficient to decrease islets hypoxia. However, to improve
      islets functionality, overoxygenation is needed. Finally, maintenance of islet
      viability and functionality for several days after isolation could improve the
      outcome of islets transplantation.

PMID- 21944583
TI  - Structure and biology of the intervertebral disk in health and disease.
AB  - The intervertebral disks along the spine provide motion and protection against
      mechanical loading. The 3 structural components, nucleus pulposus, annulus
      fibrosus, and cartilage endplate, function as a synergistic unit, though each has
      its own role. The cells within each of these components have distinct origins in
      development and morphology, producing specific extracellular matrix proteins that
      are organized into unique architectures fit for intervertebral disk function.
      This article focuses on various aspects of intervertebral disk biology and
      disruptions that could lead to diseases such as intervertebral disk degeneration.

PMID- 21944584
TI  - Intervertebral disk nutrition: a review of factors influencing concentrations of
      nutrients and metabolites.
AB  - The biomechanical behavior of the intervertebral disk ultimately depends on the
      viability and activity of a small population of resident cells that make and
      maintain the disk's extracellular matrix. Nutrients that support these cells are
      supplied by the blood vessels at the disks' margins and diffuse through the
      matrix of the avascular disk to the cells. This article reviews pathways of
      nutrient supply to these cells; examines factors that may interrupt these
      pathways, and discusses consequences for disk cell survival, disk degeneration,
      and disk repair.

PMID- 21944585
TI  - Genetics of lumbar disk degeneration: technology, study designs, and risk
      factors.
AB  - Lumbar disk degeneration (LDD) is a common musculoskeletal condition. Genetic
      risk factors have been suggested to play a major role in its cause. This article
      reviews the main research strategies that have been used to study the genetics of
      LDD, and the genes that thus far have been identified to influence susceptibility
      to LDD. With the rapid progress in genomic technologies, further advances in the
      genetics of LDD are expected in the next few years.

PMID- 21944587
TI  - Diagnostic tools and imaging methods in intervertebral disk degeneration.
AB  - Low back pain has a negative impact on the economy and society. Intervertebral
      disk degeneration is linked to the occurrence of low back pain. MRI provides
      three-dimensional morphologic and biochemical information regarding the status of
      the disk. This article reviews new and evolving MRI disk-imaging techniques,
      including grading, relaxation-time measurements, diffusion, and contrast
      perfusion. In addition, high-resolution magic-angle spinning methods to correlate
      in vitro disk degeneration (with pain, etc) and in vivo spectroscopic results are
      discussed. With the potential for morphologic and biochemical characterization of
      the intervertebral disk, MRI shows promise as a tool to quantitatively assess
      disk health.

PMID- 21944588
TI  - Management of degenerative disk disease and chronic low back pain.
AB  - Degenerative disk disease is a strong etiologic risk factor of chronic low back
      pain (LBP). A multidisciplinary approach to treatment is often warranted. Patient
      education, medication, and cognitive behavioral therapies are essential in the
      treatment of chronic LBP sufferers. Surgical intervention with a rehabilitation
      regime is sometimes advocated. Prognostic factors related to the outcome of
      different treatments include maladaptive pain coping and genetics. The
      identification of pain genes may assist in determining individuals susceptible to
      pain and in patient selection for appropriate therapy. Biologic therapies show
      promise, but clinical trials are needed before advocating their use in humans.

PMID- 21944589
TI  - Adjacent level disk disease--is it really a fusion disease?
AB  - Adjacent segment degeneration (ASD) is a relatively common phenomenon after
      spinal fusion surgery. Whether ASD is a consequence of the previous fusion or an
      individual's predisposition to continued degeneration remains unsolved to date.
      This article summarizes the existing biomechanical and clinical literature on the
      causes and clinical impact of ASD, as well as possible risk factors. Further, the
      theoretical advantage of motion-preserving technologies that aim to preserve the
      adjacent segment is discussed.

PMID- 21944586
TI  - Biomechanics of intervertebral disk degeneration.
AB  - Degenerative changes in the material properties of nucleus pulposus and anulus
      fibrosus promote changes in viscoelastic properties of the whole disc. Volume,
      pressure and hydration loss in the nucleus pulposus, disk height decreases and
      fissures in the anulus fibrosus, are some of the signs of the degenerative
      cascade that advances with age and affect, among others, spinal function and its
      stability. Much remains to be learned about how these changes affect the function
      of the motion segment and relate to symptoms such as low back pain and altered
      spinal biomechanics.

PMID- 21944590
TI  - Prosthetic total disk replacement--can we learn from total hip replacement?
AB  - Total lumbar disk replacement has become a routine procedure in many countries.
      However, discussions regarding its use are ongoing. Issues focus on patient
      selection, technical limitations, and avoidance or management of complications or
      long-term outcomes. A review of the development of this technology, since the
      development of the first successful implantation of a total lumbar disk
      prosthesis in 1984, shows an amazing analogy to the history of total hip
      replacement. This article is a one-to-one comparison of the evolution of total
      hip and total lumbar disk replacement from "skunk works" to scientific evidence.

PMID- 21944591
TI  - Stem cell regeneration of the intervertebral disk.
AB  - The use of stem cell applications has been explored and aimed at regenerating the
      intervertebral disk. The microenvironment in which cells of the intervertebral
      disk reside is harsh; however, researchers have reported on many applications for
      stem cells, including research aimed at defining and stimulating endogenous stem
      cell populations, methods to induce stem cell differentiation toward
      intervertebral disk cell phenotype in vivo, and direct transplantation of stem
      cells into damaged intervertebral disk to promote transplanted site-dependant
      differentiation. Successful results have been reported, although limitations
      remain. This article reviews the current status of stem cell research as applied
      to the intervertebral disk.

PMID- 21944592
TI  - Gene therapy for intervertebral disk degeneration.
AB  - Intervertebral disk degeneration is a common and potentially debilitating disease
      process affecting millions of Americans and other populations each year. Current
      treatments address resultant symptoms and not the underlying pathophysiology of
      disease. This has spawned the development of biologic treatments, such as gene
      therapy, which attempt to correct the imbalance between catabolism and anabolism
      within degenerating disk cells. The identification of therapeutic genes and
      development of successful delivery systems have resulted in significant advances
      in this novel treatment. Continued investigation of the pathophysiology of disk
      degeneration, however, and safety mechanisms for the application of gene therapy
      are required for clinical translation.

PMID- 21944593
TI  - Tissue engineering for intervertebral disk degeneration.
AB  - Many challenges confront intervertebral disk engineering owing to complexity and
      the presence of extraordinary stresses. Rebuilding a disk of native function
      could be useful for removal of the symptoms and correction of altered spine
      kinematics. Improvement in understanding of disk properties and techniques for
      disk engineering brings promise to the fabrication of a functional motion segment
      for the treatment of disk degeneration. Increasing sophistication of techniques
      available in biomedical sciences will bring its application into clinics. This
      review provides an account of current progress and challenges of intervertebral
      disk bioengineering and discusses means to move forward and toward bedside
      translation.

PMID- 21944595
TI  - Lumbar intervertebral disk degeneration.

PMID- 21944596
TI  - Two days in New York: reflections on the UN NCD summit.

PMID- 21944597
TI  - Nocebo side-effects in cancer treatment.

PMID- 21944594
TI  - Emerging technologies for molecular therapy for intervertebral disk degeneration.
AB  - Intervertebral disks are biologically regulated by the maintenance of a balance
      between the anabolic and catabolic activities of disk cells. Therapeutic agents,
      initially evaluated using in vitro studies on disk cells and explants, have been
      used as intradiscal injections in preclinical settings to test in vivo efficacy.
      These include anabolic growth factors, other biostimulatory agents, and
      antagonistic agents against matrix-degrading enzymes and cytokines. Additional
      work is needed to identify patient populations, using methods such as MRI, and to
      better understand the mechanism of healing. Clinical trials are underway for a
      few of these agents and other promising candidates are on the horizon.

PMID- 21944598
TI  - Congenital absence of hepatic segment IV-V in symptomatic huge abdominal cyst: an
      intraoperative anatomic liver finding never described in the literature.

PMID- 21944599
TI  - Intestinal obstruction by a bread clip.

PMID- 21944600
TI  - A long-term-lodged esophageal foreign body in an adult caused esophageal
      stricture and a mediastinal mass.

PMID- 21944601
TI  - Fatal cytomegalovirus pneumonitis and ileitis in a patient with a cardiac assist
      device.

PMID- 21944602
TI  - Recurrent giant gastrointestinal stromal tumor of the small bowel mesentery.

PMID- 21944603
TI  - Perforation after stenting of obstructing sigmoid cancer caused by acute
      angulation of the colon.

PMID- 21944605
TI  - Spontaneous hemothorax associated with costal exostoses.

PMID- 21944604
TI  - A case of sigmoid volvulus and floppy cecum: a therapeutic dilemma.

PMID- 21944606
TI  - Intentional progressive preoperative pneumoperitoneum for adhesiolysis in the
      hostile surgical abdomen.

PMID- 21944607
TI  - The consequences of late diagnosis of adnexal torsion.

PMID- 21944608
TI  - Epiploic appendagitis, an unusual cause of acute abdomen.

PMID- 21944609
TI  - Intraductal papillary mucinous neoplasm-the tip of the iceberg.

PMID- 21944610
TI  - Gallbladder agenesis with concurrent, solitary, intrahepatic biliary duct cyst.

PMID- 21944611
TI  - Heterotopic gastric mucosa: a rare cause of jejunal intussusception.

PMID- 21944612
TI  - Septic thrombophlebitis of portal vein: unusual presentation of appendicitis.

PMID- 21944613
TI  - Primary anterior abdominal wall leiomyoma.

PMID- 21944614
TI  - Gallstone ileus: a rare complication after roux-en-y gastric bypass.

PMID- 21944615
TI  - Laparoscopic multivisceral resection for infiltrating primary pancreatic non
      hodgkin's lymphoma mimicking a vast cystic neoplasm.

PMID- 21944617
TI  - John H. Gibbon, Jr., M.D.: surgical innovator, pioneer, and inspiration.

PMID- 21944618
TI  - John H. Gibbon, Jr., M.D.: surgical inventor, pioneer, and inspiration.

PMID- 21944619
TI  - Late outcomes of carotid artery stenting: a critical review.
AB  - The role of carotid artery stenting (CAS) as an alternative to carotid
      endarterectomy for the treatment of extracranial carotid occlusive disease for
      stroke prevention continues to evolve. Although technical and device refinements
      aimed at making CAS safer continue to this day, safety  as measured by 30-day and
      1-year outcomes has been the primary recipient of regulatory and practice
      attention. Relatively less emphasis has been placed on the incidence of recurrent
      stenosis after CAS and the efficacy of CAS in late stroke prevention. Data on
      late outcomes of CAS, including  factors of potential influence, have been
      emerging and are addressed in this review.

PMID- 21944620
TI  - The surgical safety checklist: lessons learned during implementation.
AB  - Procedural checklists may be useful for increasing the reliability of safety
      critical processes because of their potential capacity to improve teamwork,
      situation awareness, and error catching. To test the hypothesized utility and
      adaptability of checklists to surgical teams, we performed  a randomized
      controlled trial of procedural checklists to determine their capacity to increase
      the frequency of safety-critical behaviors during 47 laparoscopic
      cholecystectomies. Ten attending surgeons at an academic tertiary care center
      were randomized into two equal groups - half of these  surgeons received basic
      team training and used a preprocedural checklist whereas the other half performed
      standard laparoscopic cholecystectomies. All procedures were videotaped and
      scored by trained reviewers for the presence of safety-critical behaviors. There
      were no differences detected  in patient outcomes, case times, or technical
      proficiency between groups. Cases performed by surgeons in the intervention
      (checklist) group were significantly more likely to involve positive safety
      related team behaviors such as case presentations, explicit discussions of roles
      and responsibilities,  contingency planning, equipment checks, and postcase
      debriefings. Overall, situational awareness did not significantly differ between
      the intervention and control groups. Participants in the intervention (checklist)
      group consistently rated their cases as involving less satisfactory subjective 
      levels of comfort, team efficiency, and communication compared with those
      performed by surgeons in the control group. Surgical procedural safety checklists
      have the capacity to increase the frequency of positive team behaviors in the
      operating room during laparoscopic surgery. Adapting to  the use of a procedural
      checklist may be initially uncomfortable for participants.

PMID- 21944621
TI  - Gangrene therapy and antisepsis before lister: the civil war contributions of
      Middleton Goldsmith of Louisville.
AB  - It is commonly accepted that Louis Pasteur is the father of microbiology and
      Joseph Lister is the father of antisepsis. Middleton Goldsmith, a surgeon in the
      Union Army during the American Civil War, meticulously studied hospital gangrene
      and developed a revolutionary treatment regimen.  The cumulative Civil War
      hospital gangrene mortality was 45 per cent. Goldsmith's method, which he applied
      to over 330 cases, yielded a mortality under 3 per cent. His innovative work
      predated Pasteur and Lister, making his success truly remarkable and worthy of
      historical and surgical note.

PMID- 21944622
TI  - The creation of a geriatric trauma unit "G-60".
AB  - Many elderly trauma patients have isolated orthopedic injuries compounded by
      chronic medical conditions. We organized a trauma unit, led by trauma surgeons,
      that is designed to expedite the care of geriatric patients through a
      multidisciplinary approach. The development of G-60, our  Geriatric Trauma Unit,
      began with discussion between trauma surgeons and hospital administration.
      Dialogue between trauma surgeons and emergency department physicians yielded
      triaging, disposition, and admission criteria. Orthopedic surgeons helped
      implement a goal of operative management  in 48 hours. Internal medicine assisted
      in optimizing chronic disease and providing preoperative clearance with
      involvement of cardiology and anesthesiology. Meetings were held among surgeons,
      physical therapists, occupational therapists, respiratory therapists,
      nutritionists, pharmacists,  social workers, case managers, internists, a
      geriatrician, and physical medicine and rehabilitation. A unit in the hospital
      was chosen, and a paging system was implemented. Six months lapsed from inception
      to fulfillment. The multidisciplinary team has achieved several improvements in
      this  population. Through a multidisciplinary approach, a geriatric trauma unit
      was created that expedites triage, optimizes chronic illness to facilitate
      definitive management, and provides safe discharge.

PMID- 21944623
TI  - Obturator hernia revisited: surgical anatomy, embryology, diagnosis, and
      technique of repair.
AB  - Obturator hernia is the protrusion of intraperitoneal or extraperitoneal organs
      or tissues through the obturator canal. The first case was published by de Ronsil
      in 1724. Obturator hernia is more common in older malnourished women due to loss
      of supporting connective tissue and the  wider female pelvis. The hernia sac
      usually contains small bowel, especially ileum. It may follow the anterior or
      posterior division of the obturator nerve. In most cases, obturator hernia
      presents with intestinal obstruction of unknown cause. It may present with
      obturator neuralgia, as a  palpable mass or, in cases of bowel necrosis, as
      ecchymosis of the thigh. A correct diagnosis is made in 20 to 30 per cent of
      cases. CT scan is considered the gold standard for diagnosis, whereas
      ultrasonography, contrast studies, herniography and plain films are less
      specific. Surgery is  the only treatment option for obturator hernia. Hesitancy
      to intervene surgically for chronically ill patients results in high mortality.
      Transabdominal approach is indicated in cases of complete bowel obstruction or
      suspected peritonitis. The extra-abdominal approach is used in preoperatively 
      diagnosed cases and in absence of bowel strangulation. The laparoscopic approach
      is minimally invasive and effectively reduces morbidity. The defect is closed
      using sutures, tissue flaps, or prosthetic mesh.

PMID- 21944624
TI  - Temporal artery biopsy as a means of diagnosing giant cell arteritis: is there
      over-utilization?
AB  - Temporal artery biopsy (TAB) is often recommended for patients suspected of
      having temporal arteritis. The sensitivity of TAB varies widely and is dependent
      upon a number of factors (e.g., number of biopsy specimens, corticosteroid
      pretreatment, specimen length). The purpose  of this study was to determine the
      clinical utility of TAB in patients who are suspected of having giant cell
      arteritis (GCA). A retrospective review of patients who underwent TAB at Spectrum
      Health from January 1, 1998 to December 31, 2007 was performed. Forty-seven
      patients, ranging in age  from 25 to 87 years (mean: 70.7 years), underwent 53
      TABs. Females accounted for 72.3 per cent of the subjects. Positive biopsy
      results showing signs of GCA were obtained in 38.3 per cent of patients. Of
      patients who underwent biopsy, 78 per cent could have been excluded from the
      procedure  based upon individual diagnostic criteria. Positive and negative
      biopsies had average lengths of 1.84 cm and 1.29 cm, respectively (P < 0.05). In
      the community hospital setting, patients suspected of having GCA are frequently
      recommended to undergo unnecessary TAB. We advocate for  more careful selection
      of patients to undergo this diagnostic surgical procedure. In cases where TAB is
      needed, we recommend a biopsy length of > 2 cm to increase the accuracy of
      diagnosis.

PMID- 21944625
TI  - How medical alumni now see their junior clerkships in surgery.
AB  - The purpose of this study is to determine the effectiveness and value of the
      junior medical student surgical clerkship for physicians now in practice.
      Questionnaires were sent to all Mercer University School of Medicine alumni (1986
      2007) using a five-point Likert scale. One  hundred and fifty-seven responses
      were received from 873 recipients (18%), 71 per cent training in nonsurgical
      specialties. "Scrubbing in" on cases was the most valuable activity (82%),
      followed by faculty rounds (76%), resident work rounds (70%), and lectures (69%).
      Least useful  activities were question and answer sessions (54%), grand rounds
      (53%), and morbidity and mortality conferences (57%). The amount of time in the
      operating room was appropriate for 61 per cent, but to 8 per cent the operating
      room was a waste of time. Faculty evaluations gave the most effective  feedback
      (75%). Alumni in surgical specialties and obstetrics and gynecology rated their
      experiences higher than nonsurgical physicians. Overall, only 44 per cent saw the
      material learned as important to general medical education. Opinions regarding
      the value of surgical clerkships to current  practices were mixed. Undergraduate
      surgical education should emphasize common surgical conditions, surgical decision
      making, and simple procedures relevant to a nonsurgical practice.

PMID- 21944626
TI  - Factors influencing the outcome of intestinal anastomosis.
AB  - Anastomotic leak (AL) is one of the most serious complications after
      gastrointestinal surgery. All patients aged 16 years or older who underwent a
      surgery with single intestinal anastomosis at Morristown Medical Center from
      January 2006 to June 2008 were entered into a prospective database.  To compare
      the rate of AL, patients were divided into the following surgery-related groups:
      1) stapled versus hand-sewn, 2) small bowel versus large bowel, 3) right versus
      left colon, 4) emergent versus elective, 5) laparoscopic versus converted
      (laparoscopic  to open) versus open, 6) inflammatory bowel disease versus non
      inflammatory bowel disease, and 7) diverticulitis versus nondiverticulitis. We
      also looked for surgical site infection, estimated intraoperative blood loss,
      blood transfusion, comorbidities, preoperative chemotherapy,  radiation, and
      anticoagulation treatment. The overall rate of AL was 3.8 per cent. Mortality
      rate was higher among patients with ALs (13.3%) versus patients with no AL
      (1.7%). Open surgery had greater risk of AL than laparoscopic operations.
      Surgical site infection and intraoperative  blood transfusions were also
      associated with significantly higher rates of AL. Operations involving the left
      colon had greater risk of AL when compared with those of the right colon,
      sigmoid, and rectum. Prior chemotherapy, anticoagulation, and intraoperative
      blood loss all increased the AL  rates. In conclusion, we identified several
      significant risk factors for ALs. This knowledge should help us better understand
      and prevent this serious complication, which has significant morbidity and
      mortality rates.

PMID- 21944627
TI  - The diagnostic accuracy of 64-slice computed tomography in detecting clinically
      significant arterial bleeding after pelvic fractures.
AB  - The purpose of this study was to determine the diagnostic accuracy of the 64
      slice multidetector computed tomography (MDCT) in detecting active pelvic
      arterial bleeding associated with blunt pelvic fractures. We hypothesized that
      this modality yields high accuracy. We conducted a retrospective  review of all
      MDCT detected pelvic fractures over an 18-month period admitted to LAC+ USC
      Medical Center, a Level 1 trauma center. The main outcome was the presence of
      contrast extravasation (CE) on admission MDCT, consistent with clinically
      significant arterial bleeding requiring a subsequent  embolization or
      intraoperative ligation of pelvic arteries. Overall, 127 patients met study
      criteria and 12 per cent (n = 15) had CE on admission MDCT of which four were
      managed conservatively. Eighty-two per cent (n = 9) of the remaining 11 patients
      who went on to have invasive procedure  had active arterial bleeding that
      required embolization or surgical ligation. Two of the 112 (1.8%) patients
      without CE on their admission MDCT were subjected to embolization after further
      investigation with angiography as a result of the severity of their pelvic
      fracture and continuous transfusion  requirements. The calculated sensitivity,
      specificity, positive predictive value, negative predictive value, and overall
      accuracy of the 64-slice MDCT to identify clinically relevant arterial bleeding
      were 82, 95, 60, 98, and 94 per cent, respectively. The modern 64-slice MDCT
      provides relatively  high diagnostic accuracy in detecting a clinically relevant
      arterial hemorrhage after blunt pelvic fracture. Nevertheless, in patients with
      clinical signs of ongoing hemorrhage, timely angiography or operative
      intervention is warranted, even in the absence of MDCT contrast extravasation.

PMID- 21944628
TI  - Standard computed tomography of the chest, abdomen, and pelvis is sensitive and
      cost-effective for the detection of fractures of the shoulder girdle.
AB  - Computed tomography of the chest, abdomen, and pelvis (CTCAP) has become the
      mainstay of diagnosis in stable blunt trauma patients. The purpose of this study
      was to investigate whether standard CTCAP has adequate sensitivity to identify
      fractures of the scapula, clavicle, and humeral  head to replace routine
      radiographs of the shoulder. A retrospective chart review was carried out from
      January 1, 2004, to December 31, 2007, at Morristown Memorial Hospital. Inclusion
      criteria were all shoulder fracture patients in our trauma registry who underwent
      both a CTCAP and plain  radiographs of the injured shoulder. Data were collected
      for patient age, sex, Injury Severity Score, mechanism of injury, and fracture
      location. Sensitivity was calculated for each diagnostic modality as well as
      hospital costs and radiation dose of plain radiographs. A total of 374 charts 
      were reviewed and 98 patients were included in the study with a total of 117
      fractures. The sensitivity of trauma CTCAP for scapula fractures was 100 per
      cent, clavicle fractures 98 per cent, and humeral head fractures 100 per cent.
      The sensitivity of the shoulder series for scapula fractures  was 60 per cent,
      clavicle fractures 85 per cent, and humeral head fractures 100 per cent. The
      plain radiographs added $298 in hospital charges and 0.191 mSv of radiation per
      patient. CTCAP is a sensitive tool for identifying fractures in the shoulder
      girdle. Therefore, CTCAP can replace  the routine radiographs of the shoulder
      resulting in less total radiation exposure of the trauma patients. This also
      would lead to lower healthcare cost and better diagnostic workflow.

PMID- 21944629
TI  - Evaluation of hemostatic factors in patients undergoing major hepatic resection
      and other major abdominal surgeries.
AB  - The aim of this study was to evaluate the role for additional testing of
      coagulation in perioperative management of patients undergoing major hepatic
      resection. Major outcome measures were perioperative measurements of hemostatic
      factors (activated partial prothrombin time [aPTT], prothrombin 
      time/international normalized ratio, fibrinogen, antithrombin-III). We conducted
      a prospective, single-blind study comparing hemostatic factors in patients
      undergoing major hepatectomy, Whipple procedures, and other gastrointestinal
      operations. Ninety-five consecutive patients were enrolled.  No values differed
      significantly at baseline. Immediately postoperative, only international
      normalized ratio was significantly lower comparing major hepatectomy with Whipple
      (P < 0.005) and other procedures (P < 0.0032). Twenty-four hours postoperative,
      antithrombin-III  was lower for major hepatectomy than Whipple (P < 0.028) and
      others (P < 0.0001); fibrinogen was lower compared with Whipple (P < 0.014) and
      others (P < 0.0009); international normalized ratio was lower to compared with
      Whipple (P < 0.0001)  and others (P < 0.0001). aPTT measurements never differed
      significantly between groups at any time. Antithrombin-III and fibrinogen only
      correlated with international normalized ratio and aPTT for the other procedures.
      Additional hemostatic values beyond the standard evaluations  of aPTT and
      international normalized ratio are needed to better assess patients undergoing
      major hepatic surgery.

PMID- 21944630
TI  - Proteinuria as a predictor of renal dysfunction in trauma patients receiving
      intravenous contrast.
AB  - Trauma patients have unknown comorbidities, multiple injuries, and incomplete
      laboratory testing, yet require contrast-enhanced imaging to identify potentially
      life-threatening problems. Our goal was to characterize contrast-induced
      nephropathy (CIN) in this population. We retrospectively reviewed characteristics
      of 402 patients who presented to a Level II trauma center and received contrast
      enhanced imaging. CIN was defined as creatinine rise of 0.5 mg/dL or greater or
      25 per cent or greater from baseline within 48 hours. CIN occurred in 7.7 per
      cent and four patients required hemodialysis. Patients with CIN were older, had
      lower admission hemoglobin, higher Injury Severity Score, and received more blood
      products. Factors that predicted CIN included: male sex, age older than 46 years,
      body mass index less than 27 kg/m2, glomerular filtration rate less than 109
      mL/min/1.73 m2, hemoglobin less than 12 mg/dL, hematocrit less than 36 per cent,
      proteinuria, 2 units or more of fresh-frozen plasma in 48 hours, and alcohol use.
      Odds ratio for developing CIN with two, five, or six of these factors was 3.39,
      6.54, and 8.38, respectively. A match-controlled analysis for Injury Severity
      Score and age in patients with CIN versus non-CIN patients revealed the strongest
      predictor of CIN was proteinuria (relative risk, 2.5; confidence interval, 1.1 to
      5.8). Although it is difficult to truly differentiate CIN from renal dysfunction
      related to injury severity in trauma patients, proteinuria may be an important
      factor in identifying nephropathy in this population.

PMID- 21944631
TI  - Does patient age and height of fall alone require trauma team activation?
AB  - Our American College of Surgeons Level I trauma center uses physiological data
      and injury patterns to identify fall patients at risk. We hypothesized that
      height of fall and patient age impacted injury severity and analyzed if they were
      significant predictors of the need for trauma  team activation. Charts were
      reviewed from July 1, 2004, to June 30, 2007, for age; sex; Injury Severity Score
      (ISS); height of fall and admission to the intensive care unit, operating room,
      stepdown unit, floor; or death. Exclusion criteria were physiological,
      neurologic, or airway compromise  and penetrating neck or torso injuries. ISS was
      used as a positive control. A total of 1865 fall patients were treated during the
      period of data collection, and 1348 patients were eliminated by exclusion
      criteria, leaving 517 patients for study. Although patient age did not correlate
      with  the need for trauma team activation, there was a statistically significant
      association between age and admission to the hospital from the emergency room (P
      < 0.05; area under curve [AUC] = 0.713; 95% confidence interval [CI], 0.656 to
      0.770). Similarly, although the height of fall  alone did not have a significant
      predictive value for the need of trauma team activation, there was a clear
      association of the height of fall with hospital admission (AUC = 0.589; 95% CI,
      0.519 to 0.658). Patient age and height of fall alone are not criteria for trauma
      team activation in the  absence of physiological, neurologic, or airway
      compromise.

PMID- 21944632
TI  - Sutures versus staples for the management of surgical wounds: a meta-analysis of
      randomized controlled trials.
AB  - Surgical sutures are conventionally used in skin closure of surgical wounds.
      Alternative wound closure techniques include staples and adhesive strips. We
      aimed to evaluate sutures versus staples as methods of surgical wound closure by
      performing a meta-analysis. We searched PubMed,  Scopus, and Cochrane Central
      Register of Controlled Trials for randomized controlled trials that compared
      sutures with staples for surgical wound closure. Trials referring to orthopedic
      operations were excluded. Twenty studies (involving a total of 2111 patients)
      were included. Five studies  referred to obstetrics/gynecological operations,
      seven to general surgery, four to emergency care treatment, three to head/neck
      operations, and one to vascular surgery. Regarding the time needed for wound
      closure, staples were superior to sutures; the mean difference observed between
      the sutures  and staples groups was 5.56 minutes per wound (95% confidence
      intervals [CI], 0.05 to 11.07). Wound infections were significantly fewer in the
      staples group compared with the sutures group(s) (12 studies, 1529 patients; odds
      ratio, 2.06; 95% CI, 1.20 to 3.51). In five studies, the use of staples  was
      associated with significantly more pain compared with sutures. The majority of
      studies with available relevant data reported nonsignificant differences
      regarding the cosmetic result and patient's satisfaction. Our findings suggest
      that staples are associated with fewer wound infections  compared with sutures in
      the evaluated types of surgery. However, in a rather limited number of studies,
      the use of staples was associated with more pain. Further studies incorporating
      more objective methods for assessment cosmetic and patient satisfaction are
      required to clarify this issue.

PMID- 21944633
TI  - Institutional results and meta-analysis of outcome after infrainguinal surgical
      revascularization in patients greater than 80 years old.
AB  - Our aim was to evaluate the outcome after infrainguinal bypass revascularization
      in patients greater than 80 years old with lower limb ischemia treated at our
      institution and to perform a meta-analysis of literature data to better estimate
      current postoperative results. Eighty-four  infrainguinal bypass procedures were
      performed in 76 patients of at least 80 years of age. Major outcome end points
      included survival, limb salvage, and amputation-free survival. Systematic review
      and meta-analysis of literature data on immediate and late outcome in patients
      older than 80  years who underwent infrainguinal surgical revascularization have
      been performed. At 30 days, seven patients (8.3%) died and seven major
      amputations (8.3%) occurred. Kaplan-Meier estimates of survival at 1, 3, and 5 
      years were 73.8, 59.8, and 43.1 per cent; leg salvage 78.9, 71.4, and 67.8  per
      cent; and amputation-free survival 58.3, 42.7, and 28.2 per cent, respectively.
      The mean survival was 4.6 +/- 0.4 years. Only Finnvasc score greater than 2 was
      predictive of poor late amputation-free survival (at 5 years: 4.5 vs 42.3%;
      relative risk, 2.19; 95% confidence interval,  1.27 to 3.76). Eleven studies were
      additionally available for analysis. Pooled estimates of survival at 30 days, 1
      year, and 5 years were 94.8, 86.0, and 47.6 per cent, respectively, and of leg
      salvage were 95.5, 84.7, and 84.1 per cent, respectively. Infrainguinal bypass in
      patients older  than 80 years carries a significant operative risk and is
      associated with suboptimal long-term amputation-free survival, which is
      particularly poor among patients with a Finnvasc score greater than 2.

PMID- 21944634
TI  - Lateral congenital anomalies of the pharyngeal apparatus: part I. Normal
      developmental anatomy (embryogenesis) for the surgeon.
AB  - Knowledge of the embryogenesis of the pharyngeal apparatus is the only means of
      understanding the "architecture" of the neck. The embryonic pharynx (which
      includes future oral and nasal cavities) is a much more extensive area than the
      adult pharynx. The main feature of the  developing pharynx is a series of arches,
      internal pouches, and external clefts, which together comprise the pharyngeal
      apparatus. This structure is associated with other developing splanchna of the
      neck, e.g., the thyroid and parathyroid glands, tonsils, and thymus. Within each
      of the pharyngeal  arches are the developing aortic arches and, specific for each
      arch, cranial nerves. The complex relations of the mesenchymal derivatives of
      arches (muscles, cartilage, bones) with the neurovascular bundles within each
      arch are presented and explained. The pharyngeal apparatus undergoes dramatic 
      transformations: pouches and clefts disappear without interruption (interruption
      would produce gills and support the misnomer "branchial apparatus"). In addition,
      in the lateroventral neck, somites migrate to produce other muscles such as
      sternocleidomastoid and trapezius innervated  by spinal nerves. Lateral
      congenital anomalies largely rely on persistence of a cleft/and or pouch or
      communication between the two. Their tracts have a "crooked" course among other
      entities generated by alterations that take place during embryogenesis.

PMID- 21944635
TI  - Lateral congenital anomalies of the pharyngeal apparatus: part II. anatomy of the
      abnormal for the surgeon.
AB  - "Anatomy of the abnormal"-a branch of surgical anatomy-deals with relations of an
      anomaly to surrounding entities. Here, lateral congenital anomalies of the
      pharyngeal apparatus are examined; their relations to entities of the neck can be
      explained embryologically.  Location of embryonic pharyngeal arches, clefts, and
      pouches in the adult is presented and terminology of these anomalies (fistulas,
      sinuses, cysts) is defined. First "cleft and pouch" anomalies relate with the
      parotid and facial nerve. Second cleft and pouch anomalies course deeply  to
      second arch structures and superficially to third arch structures. Consequently,
      they relate with hypoglossal and glossopharyngeal nerves and internal and
      external carotid arteries. Third cleft and pouch anomalies pass deep to third
      arch entities and superficial to those of the fourth arch  and relate with
      glossopharyngeal, hypoglossal, superior and recurrent laryngeal nerves, and the
      internal carotid artery. The complicated course of fourth cleft and pouch
      anomalies brings them into relationship with glossopharyngeal, hypoglossal,
      superior and recurrent nerves, internal carotid,  aorta, and subclavian arteries.
      Found superficially are veins (external and anterior jugular, common facial,
      communicating), nerves (transverse cervical, great auricular, mandibular,
      cervical branches of facial), and relevant spinal nerves (e.g., accessory).
      Knowledge of these anatomical relations  helps prevent anatomical complications.

PMID- 21944636
TI  - Lateral congenital anomalies of the pharyngeal apparatus: part III. cadaveric
      representation of the course of second and third cleft and pouch fistulas.
AB  - "Stepladder" surgery for fistula from second or third pharyngeal cleft and pouch
      is "blind." Neither intraoperative methylene blue injection and probing nor
      preoperative imaging (fistulogram ultrasound, computed tomography, magnetic
      resonance imaging) reveal  three-dimensional anatomic relations of fistulas. This
      article describes the most common second and third fistula courses and
      demonstrates representation of their tracts with wires in human cadavers. A
      second cleft and pouch fistula, at its external opening, pierces superficial
      cervical fascia  (and platysma), then investing cervical fascia, and travels
      under the sternocleidomastoid muscle, superficial to the sternohyoid and anterior
      belly of omohyoid. It ascends along the carotid sheath, and at the upper border
      of the thyroid cartilage it pierces the pretracheal fascia. Characteristically, 
      it courses between the carotid bifurcation and over the hypoglossal nerve. After
      passing beneath the posterior belly of the digastric muscle and the stylohyoid,
      it hooks around both glossopharyngeal nerve and stylopharyngeus muscle. The
      fistula reaches the pharynx below the superior constrictor  muscle. The course of
      a third cleft and pouch fistula is similar until it has pierced pretracheal
      fascia; then it passes over the hypoglossal nerve and behind the internal
      carotid, finally descending parallel to the superior laryngeal nerve, reaching
      the thyrohyoid membrane cranial to the  nerve.

PMID- 21944637
TI  - Perforation and expulsion through the anus of catheter after gastric banding.

PMID- 21944638
TI  - Primary lipoma of the adrenal gland.

PMID- 21944639
TI  - A duodenal duplication cyst causing recurrent pancreatitis in a young patient.

PMID- 21944640
TI  - Kidney transplantation over the age of 65: a single-center experience.

PMID- 21944641
TI  - Reconstruction after pancreaticoduodenectomy: a new approach to an ongoing
      dispute.

PMID- 21944642
TI  - Ductal carcinoma in situ and bilateral atypical ductal hyperplasia in a 23-year
      old man with gynecomastia.

PMID- 21944643
TI  - Extrarectal colonic adenocarcinoma after remote pull-through for an imperforate
      anus.

PMID- 21944644
TI  - Outcome of treatment of liver metastasis after curative surgery for gastric
      cancer.

PMID- 21944645
TI  - Indication of emergency operation and intensive care for cardiopulmonary arrest
      related with gastrointestinal perforation.

PMID- 21944646
TI  - Debunking the experience versus expertise debate in surgical specialties.

PMID- 21944647
TI  - Ending medical complicity in state-sponsored torture.

PMID- 21944648
TI  - Extensive diversity of intestinal trichomonads of non-human primates.
AB  - Despite the fact that the non-human primates are our closest relatives and
      represent a species-rich mammalian group, little is known about their intestinal
      protistan parasites/commensals. Particularly, the intestinal trichomonads
      represent a neglected part of the fauna of the primate digestive system. We have
      established 30 trichomonad strains isolated from feces of 11 primate species kept
      in 3 Czech zoos and performed an analysis of their SSU rDNA and ITS1-5.8S rDNA
      ITS2. Our results showed that intestinal trichomonads are rather common among non
      human primates. Molecular phylogenetic analysis showed that the strains are
      unexpectedly diversified, belonging to 8 or 9 distinct species. Interestingly,
      the vast majority of the strains from non-human primates belonged to the genus
      Tetratrichomonas while no member of this genus has been found in the human
      intestine so far. In addition, hominoid and non-hominoid primates differed in
      their intestinal trichomonads. Our results suggest that captive primates possibly
      may be infected by intestinal trichomonads of other vertebrates such as pigs,
      cattle, birds, tortoises and lizards.

PMID- 21944649
TI  - The post-auricular approach for gap arthroplasty - a clinical investigation.
AB  - Objective of this prospective study was to evaluate and compare posterior
      auricular approach for surgery of temporomandibular joint ankylosis with
      preauricular approach. These evaluations were done on the basis of certain
      parameters like incidences of facial nerve injury, time taken to expose ankylotic
      mass, haemorrhage and quality of exposure of joint and surrounding structures.
      This study was conducted among 15 patients of temporomandibular joint ankylosis.
      A total number of 30 joints were operated. These joints were divided in two
      groups i.e. Group A - preauricular group, Group B - postauricular group. Fifteen
      joints were operated in each group. Age of patients was in range of 4-65 years.
      All the patients were operated under general anesthesia. Preoperative,
      intraoperative and postoperative evaluations were done according to parameters.
      Patients were recalled up to 3 months for observations. Results have shown that
      in postauricular group incidences of facial nerve injury was significantly less,
      more time was taken to expose the ankylotic mass, incidences of haemorrhage was
      more and exposure of structures anterior to joint was difficult. Whereas
      preauricular approach is less time consuming, incidence of facial nerve damage is
      higher, exposure of structures anterior to joint is good and intraoperative
      incidences of haemorrhage is less.

PMID- 21944650
TI  - [Prevalence of chronic kidney disease in hypertensive aged women treated in
      primary care. MERICAP Study].
AB  - BACKGROUND AND OBJECTIVES: Information about the prevalence of chronic kidney
      disease (CKD) in the population treated in primary care is scarce. The aim of
      this study was to assess the prevalence of CKD in Spanish hypertensive women aged
      64 years or older, and to determine possible associated factors. PATIENTS AND
      METHOD: Cross-sectional study including women with a diagnosis of hypertension
      selected by consecutive sampling in primary care. CKD was diagnosed when
      glomerular filtration rate was<60 ml/min/1.73 m(2) (MDRD). We assessed
      sociodemographic and clinical data, cardiovascular risk factors, and the presence
      of cardiovascular disease. RESULTS: The sample included 3782 women with a mean
      age of 73.6 +/- 6.1 years. CKD (glomerular filtration rate<60 ml/min/1.73 m(2)
      was present in 53.4% (95% CI: 51.8-55.0). Masked CKD (serum creatinine<1.2mg/dl)
      was present in 25.7% (95% CI: 26.3-29.1). The prevalence increased with age (51%
      in those younger than 75 and 60.7% in women older than 84 (P<.001). With respect
      to those with normal renal function, hypertensive women having CKD were older,
      showed higher values of blood pressure, and had more frequently dyslipidemia,
      elevated plasma glucose, target organ damage and cardiovascular disease (P<.001).
      In a multivariate analysis, CKD was associated with coronary heart disease (OR:
      1.9), hyperglycemia (OR: 1.6), hypertriglyceridemia (OR: 1.5), and elevated
      diastolic blood pressure (OR: 1.4). CONCLUSIONS: More than half of hypertensive
      women aged 64 years have CKD and of these about half have normal creatinine
      values.

PMID- 21944651
TI  - [Community acquired Stenotrophomonas maltophilia soft-tissue infection in a
      previously healthy patient].

PMID- 21944652
TI  - [Electrocardiographic alterations suggestive of acute myocardial infarction in a
      patient with Chagas disease].

PMID- 21944653
TI  - Acupuncture in children and adolescents with bronchial asthma: a randomised
      controlled study.
AB  - OBJECTIVE: This randomised controlled trial evaluates the immediate effects of
      acupuncture as an add-on therapy in in-patient rehabilitation of children and
      adolescents with bronchial asthma. PATIENTS AND METHODS: In a pre-post design,
      the severity of symptoms, lung function, illness-specific quality of life
      (Paediatric Asthma Quality of Life Questionnaire - PAQLQ) and general and asthma
      specific level of anxiety (State-Trait Anxiety Inventory for Children - STAIC)
      were investigated in 46 acupuncture and 47 control patients. In addition to
      asthma sports, climate therapy and behavioural training, the intervention group
      received acupuncture treatment with a standardised needle pattern (12 * 30 min.).
      RESULTS: With acupuncture, the peak expiratory flow variability differs
      significantly (p<0.01) from that of the control patients' group. Moreover, the
      acupuncture group differs significantly in their rehabilitation response at the
      time of discharge concerning perceived anxiety (STAIC-S). The lung function tests
      do not present differences between groups. CONCLUSION: After additional
      acupuncture, amelioration of peak expiratory flow variability and anxiety can be
      shown, without any difference in objective lung function tests and quality of
      life between study groups. Further studies might evaluate the effects of
      acupuncture on childhood asthma in an outpatient setting.

PMID- 21944654
TI  - The impact of eurythmy therapy on stress coping strategies and health-related
      quality of life in healthy, moderately stressed adults.
AB  - BACKGROUND: 'Stress' and 'health-related quality of life' (HRQoL) are two
      important theoretical constructs for modern therapy evaluation with clinical
      relevance. Eurythmy therapy (EYT) is a mind-body-therapy derived from
      anthroposophic medicine with promising effects on heart rate variability (HRV),
      HRQoL and disease scores. The purpose of this study was to investigate the impact
      of EYT on stress coping strategies (SCS) and HRQoL in a controlled study with
      moderately stressed participants. METHODS: 68 healthy, moderately stressed adults
      (mean age: 42.2; SD: 8.2) performed 10h of EYT in a group setting over a period
      of six weeks. A non-randomised control group of 22 healthy adults (mean age:
      43.6; SD: 13.7) received no intervention and did only complete the questionnaires
      at the same data points. Outcomes were measured before and after the intervention
      (AVEM & SF-36). RESULTS: A significant impact on SCS was found in seven AVEM
      scales (MANOVA, F (1/74)=4.59; p=.04). With regard to changes in risk pattern
      affiliation (AVEM), 24% of the participants receiving EYT (n=55) changed over
      time from a risky stress coping pattern to a healthier pattern. Concerning the
      HRQoL four normally distributed scales of the SF-36 ('vitality', 'social
      functioning', 'mental health' and 'physical functioning') showed a significant
      group*time interaction favouring the EYT group (MANOVA, F (1/74)=17.26; p<.001).
      Statistically and clinically relevant mean differences over time of at least
      eight scale points were found for 'role physical', 'bodily pain', 'vitality' and
      'mental health', and of at least 15 scale points for 'role emotional' and 'social
      functioning'. CONCLUSIONS: A six-week period of EYT training can result in a
      significant reduction of stress and consequently improve QoL. Because a
      significant proportion of participants had high levels of stress at baseline the
      results suggest a health-enhancing benefit of EYT that may have clinical
      potential for prevention of stress and associated disorders in healthy
      individuals and possibly in patients with chronic diseases, for example.

PMID- 21944655
TI  - Use of acupuncture therapy as a supplement to conventional medical treatments for
      acute ischaemic stroke patients in an academic medical centre in Korea.
AB  - OBJECTIVES: Acupuncture has served as a major complementary and alternative
      therapy that supplements conventional medicine and is the subject of growing
      public interest. This study was conducted to estimate the usage rate of
      acupuncture as a supplemental treatment in acute ischaemic stroke patients and to
      identify factors associated with the choice to use this therapy. METHODS: Using
      the registry of stroke patients admitted to an academic medical centre in Korea,
      the use of acupuncture therapy was recorded and analysed, along with the
      patients' socio-demographic characteristics, hospital access variables, risk
      factors for ischaemic stroke and clinical characteristics. The data were analysed
      using descriptive statistics, chi-square tests and multiple logistic regression
      analyses. RESULTS: Of 2167 patients, 18% received acupuncture therapy. The choice
      of acupuncture therapy was significantly associated with stroke severity as well
      as gender, age, geographical residence and previous history of stroke. After
      controlling for other significant factors, there was an approximately 3.4-fold
      greater usage in patients with moderately severe strokes (95% confidence interval
      (CI)=2.5-4.6) and 4.1-fold greater usage in patients with severe strokes (95%
      CI=2.7-6.4). CONCLUSIONS: The findings provide a better understanding of
      patients' utilization of acupuncture therapy as a supplement to conventional
      medical treatments and of factors associated with the utilization of acupuncture
      in patients with acute ischemic stroke. Strategic implications of acupuncture
      therapy are suggested for both health-care providers and policy makers.

PMID- 21944656
TI  - A comparison of the effectiveness between Western medicine and Chinese medicine
      outpatient consultations in primary care.
AB  - BACKGROUND: Traditional Chinese medicine (TCM) plays an important role in the
      primary care system in many places, but research evidence on its effectiveness is
      largely lacking. The aim of the present study was to compare the effectiveness
      between TCM and Western medicine (WM) consultations in primary care. OBJECTIVES:
      To evaluate whether medical consultations could improve the quality of life and
      health condition of patients in primary care and to find out whether there was
      any difference in the effectiveness bewteen TCM and WM. DESIGN, SETTING AND
      SUBJECTS: This was a prospective, longitudinal study on 290 patients of one TCM
      public and 841 patients of two WM general outpatient clinics (GOPC) in Hong Kong
      when they consulted for an episodic illness. METHODS: All patients attending a
      TCM GOPC in TWH, and the two WM GOPC (TWH and ALC), who fullfilled the inclusion
      criteria were invited to participate. Each patient answered a structured
      questionnaire on the presenting complaint, socio-demography, chronic morbidity
      and service utilization, the Chinese Quality of Life instrument (ChQOL) and the
      SF-36V2 Health Survey immediately before and two weeks after the doctor
      consultation. The Global Rating on change Scale (GRS) was also administered in
      the week 2 assessment. OUTCOME MEASURES: The primary outcomes were changes in the
      ChQOL and SF-36V2 HRQOL scores. Secondary outcomes included the GRS score. The
      significance of the change within individual were tested by paired t-tests. The
      differences in change in scores between WM and TCM were tested by independent
      sample-t-tests or chi-square, as appropriate. Multivariate regresions were used
      to determine the independent effect of type of medicine on the change in HRQOL
      scores. RESULTS: Mean ChQOL and SF-36V2 scores of subjects improved significantly
      two weeks after TCM or WM consultations in all domains except for the Physical
      form domain of ChQOL. The greatest improvements were found in the SF-36V2
      physical-health related domains. 78% TCM clinics and 71% of subjects WM clinics
      reported an improvement in GRS. The proportion of subjects who had improvement in
      HRQOL scores were lower among subjects consulting the WM clinic (72.3%) than
      those consulting TCM clinics (100%) but the difference was not significant after
      correction for baseline scores. CONCLUSIONS: Both TCM and WM consultations were
      associated with significant improvement in HRQOL in over 90% of patients. There
      was no singificant difference between the effectiveness of TCM and WM
      consultations. The results support the role of TCM as an alternative primary care
      service in Hong Kong.

PMID- 21944657
TI  - Arnica and stinging nettle for treating burns - a self-experiment.
AB  - BACKGROUND AND OBJECTIVE: Combudoron, composed of extracts from arnica and
      stinging nettle, is used for the treatment of partial thickness burns and insect
      bites in Europe. Because clinical investigations are lacking we wanted to
      investigate its efficacy in partial thickness burns. METHODS: Two individuals
      performed a self experiment: 4 experimental grade 2 burns (each 1 cm(2)) on the
      back were induced respectively with an erbium YAG-laser. Wounds were treated with
      Combudoron gel, Combudoron liquid, placebo gel or placebo liquid in each of the
      subjects in a standardized, single blind manner. Outcome parameters were the
      photo documented duration of wound healing and visual analogue scale (VAS) pain
      scores. RESULTS: All 8 experimental burns were similar from size and depth at
      baseline. Eschars of the verum-treated burns fell off earlier than the placebo
      treated burns (verum liquid: after 14 and 19 days compared to 17 and 27 days with
      placebo liquid. Verum gel: after 16 and 22 days compared to 18 and 28 days with
      placebo gel). Eschars of the liquid treated burns fell off earlier than of the
      gel treated burns. Pain scores were not applicable because they were low and
      differences between the lesions could not be discriminated on the back.
      CONCLUSION: Combudoron seems to have positive effects on healing of grade 2 laser
      induced burns which deserve further investigation.

PMID- 21944658
TI  - Is yoga effective for pain? A systematic review of randomized clinical trials.
AB  - OBJECTIVE: The objective of this systematic review was to assess the
      effectiveness of yoga as a treatment option for any type of pain. METHOD: Seven
      databases were searched from their inception to February 2011. Randomized
      clinical trials were considered if they investigated yoga in patients with any
      type of pain and if they assessed pain as a primary outcome measure. The 5-point
      Jadad scale was used to assess methodological quality of studies. The selection
      of studies, data extraction and quality assessment were performed independently
      by two reviewers. RESULTS: Ten randomized clinical trials (RCTs) met the
      inclusion criteria. Their methodological quality ranged between 1 and 4 on the
      Jadad scale. Nine RCTs suggested that yoga leads to a significantly greater
      reduction in pain than various control interventions such as standard care, self
      care, therapeutic exercises, relaxing yoga, touch and manipulation, or no
      intervention. One RCT failed to provide between group differences in pain scores.
      CONCLUSIONS: It is concluded that yoga has the potential for alleviating pain.
      However, definitive judgments are not possible.

PMID- 21944659
TI  - Six months to go: or a 2012 story that may have passed you by.

PMID- 21944660
TI  - [Editorial].

PMID- 21944661
TI  - Small molecular anticancer agent SKLB703 induces apoptosis in human
      hepatocellular carcinoma cells via the mitochondrial apoptotic pathway invitro
      and inhibits tumor growth invivo.
AB  - Inducing apoptosis is a promising therapeutic approach to overcome cancer. Here
      we described that a novel synthesized compound, 3-amino-N-(4-chlorobenzyl)-6-(3
      methoxyphenyl)thieno[2,3-b]pyridine-2-carboxamide (SKLB703), exhibits antitumor
      activity via inducing apoptosis both invitro and invivo. Our results showed that
      SKLB703 inhibited the proliferation of a panel of human cancer cell lines, and
      human hepatocellular carcinoma cell line HepG2 was the most sensitive. The
      proliferation inhibitory effect of SKLB703 was associated with its apoptosis
      inducing effect by activating caspase-3 and caspase-9 rather than caspase 8.
      Exposure of HepG2 to SKLB703 also resulted in Bax upregulation, Bcl-2
      downregulation, cytochrome c release and mitochondrial transmembrane potential
      change in mitochondrial apoptotic pathway. Moreover, the decrease of
      phosphorylated p 44/42 mitogen-activated protein kinase and phosphorylated Akt
      was observed. SKLB703 suppressed the growth of established tumors in xenograft
      models in mice, whereas no toxicity was exhibited. TUNAL analysis showed that
      SKLB703 induced HepG2 tumor apoptosis. Taken together, the present study
      demonstrates that SKLB730 exhibits its antitumor activity through inducing
      apoptosis via mitochondrial apoptotic pathway. Its potential to be a candidate of
      anticancer agent is worth being further investigated.

PMID- 21944662
TI  - Aerobic bacterial, coliform, Escherichia coli and Staphylococcus aureus counts of
      raw and processed milk from selected smallholder dairy farms of Zimbabwe.
AB  - A cross sectional study was conducted to enumerate total viable bacteria (TBC),
      coliforms, Escherichia coli and Staphylococcus aureus in raw (n=120) and
      processed (n=20) milk from individual farms from three smallholder dairy schemes
      of Zimbabwe between October, 2009 and February, 2010. Data on management factors
      were collected using a structured questionnaire. A standard pour plate technique
      was used to enumerate total viable bacteria, while for coliforms, E. coli and S.
      aureus, counts were assessed by the spread plate technique. The association of
      total viable bacterial counts and management factors was assessed using
      univariable and a linear regression model. The log10 TBC for raw milk differed
      significantly (P<0.05) amongst the schemes with the lowest (5.6+/-4.7 log10
      cfu/ml) and highest (6.7+/-5.8 log10 cfu/ml) recorded from Marirangwe and Nharira
      respectively. The mean log10 of TBC of processed milk (6.6+/-6.0 log10 cfu/ml)
      were marginally higher than those of raw milk (6.4+/-5.6 log10 cfu/ml) but not
      significant (P>0.05). The coliform, E. coli and S. aureus counts for raw milk
      significantly differed (P<0.05) amongst the study areas. The variation in TBC,
      coliforms, E. coli and S. aureus counts amongst the schemes could be attributed
      to differences in milking hygiene where farms with more access to training and
      monitoring of microbiological quality of milk had lower counts. Linear regression
      analysis revealed dairy scheme, delivery time and season of milking as
      independently associated with increased TBC of raw milk. The high TBC of raw and
      processed milk generally indicated low levels of milking hygienic practices, and
      high level of post-processing contamination, respectively. The high TBC,
      coliform, E. coli and S. aureus counts of both raw and processed milk may present
      a public health hazard. Thus, educating the farmers on general hygienic
      practices, quickening the delivery of milk to collection centres, or availing
      cooling facilities on-farm will improve the microbiological quality and safety of
      milk.

PMID- 21944663
TI  - Predialysis serum sodium level, dialysate sodium, and mortality in maintenance
      hemodialysis patients: the Dialysis Outcomes and Practice Patterns Study (DOPPS).
AB  - BACKGROUND: Predialysis serum sodium concentrations recently have been linked to
      patient characteristics and outcomes in hemodialysis patients and may have
      implications for the dialysate sodium prescription. STUDY DESIGN: Prospective
      cohort study. PARTICIPANTS: 11,555 patients from 12 countries in the Dialysis
      Outcomes and Practice Patterns Study (DOPPS), phases I (1996-2001) and III (2005
      2008). PREDICTORS: Demographics, comorbid conditions, laboratory measurements
      (model 1); mean serum sodium level, dialysate sodium concentration (model 2).
      OUTCOMES: Serum sodium level, using adjusted linear mixed models (model 1); all
      cause mortality, using Cox proportional hazards models (model 2). RESULTS: Median
      follow-up was 12 months, with 1,727 deaths (15%) occurring during the study
      period (12,274 patient-years). Mean serum sodium level in the DOPPS countries was
      138.5 +/- 2.8 mEq/L. Japan had the highest (139.1 +/- 2.6 mEq/L) and
      Australia/New Zealand had the lowest mean serum sodium level (137.4 +/- 2.8
      mEq/L). Serum sodium level was associated positively with male sex, black race,
      body mass index, serum albumin level, and creatinine level and negatively with
      neurologic and psychiatric disease, white blood cell count, and intradialytic
      weight loss (0.16 mEq/L lower per 1% loss). Higher serum sodium level was
      associated with lower adjusted all-cause mortality in a continuous model (HR,
      0.95 per 1 mEq/L higher; 95% CI, 0.93-0.97). Dialysate sodium prescription was
      not associated with serum sodium level. Mortality analyses restricted to the
      serum sodium tertile with the highest mortality (serum sodium <137 mEq/L) showed
      lower mortality risk in patients with dialysate sodium prescriptions >140 mEq/L.
      LIMITATIONS: Causality cannot be established in this observational study, which
      does not consider potential effects of dialysate sodium level on postdialysis
      thirst, dietary salt and water intake, interdialytic weight gain, and
      cardiovascular stability. CONCLUSIONS: Lower serum sodium levels are associated
      with certain hemodialysis patient characteristics and higher adjusted risk of
      death. The lower mortality observed in our adjusted analyses in patients with
      serum sodium levels <137 mEq/L dialyzed against dialysate sodium prescriptions
      >140 mEq/L is intriguing, may be related to intradialytic cardiovascular
      stability, and deserves further study.

PMID- 21944664
TI  - Use of clinical decision support systems for kidney-related drug prescribing: a
      systematic review.
AB  - BACKGROUND: Clinical decision support systems (CDSSs) have the potential to
      improve kidney-related drug prescribing by supporting the appropriate initiation,
      modification, monitoring, or discontinuation of drug therapy. STUDY DESIGN:
      Systematic review. We identified studies by searching multiple bibliographic
      databases (eg, MEDLINE and EMBASE), conference proceedings, and reference lists
      of all included studies. SETTING & POPULATION: CDSSs used in hospital or
      outpatient settings for acute kidney injury and chronic kidney disease, including
      end-stage renal disease (chronic dialysis patients or transplant recipients).
      SELECTION CRITERIA FOR STUDIES: Studies prospectively using CDSSs to aid in
      kidney-related drug prescribing. INTERVENTION: Computerized or manual CDSSs.
      OUTCOMES: Clinician prescribing and patient-important outcomes as reported by
      primary study investigators. CDSS characteristics, such as whether the system was
      computerized, and system setting. RESULTS: We identified 32 studies. In 17
      studies, CDSSs were computerized, and in 15 studies, they were manual pharmacist
      based systems. Systems intervened by prompting for drug dosing adjustments in
      relation to the level of decreased kidney function (25 studies) or in response to
      serum drug concentrations or a clinical parameter (7 studies). They were used
      most in academic hospital settings. For computerized CDSSs, clinician prescribing
      outcomes (eg, frequency of appropriate dosing) were considered in 11 studies,
      with all 11 reporting statistically significant improvements. Similarly, manual
      CDSSs that incorporated clinician prescribing outcomes showed statistically
      significant improvements in 6 of 8 studies. Patient-important outcomes (eg,
      adverse drug events) were considered in 7 studies of computerized CDSSs, with
      statistically significant improvements in 2 studies. For manual CDSSs, 6 studies
      measured patient-important outcomes and 5 reported statistically significant
      improvements. Cost-savings also were reported, mostly for manual CDSSs.
      LIMITATIONS: Studies were heterogeneous in design and often limited by the
      evaluation method used. Benefits of CDSSs may be reported selectively in this
      literature. CONCLUSION: CDSSs are available for many dimensions of kidney-related
      drug prescribing, and results are promising. Additional high-quality evaluations
      will guide their optimal use.

PMID- 21944665
TI  - Appraising stroke risk in maintenance hemodialysis patients: a large single
      center cohort study.
AB  - BACKGROUND: Stroke incidence in hemodialysis patients is up to 10 times greater
      than in the general population and is associated with a worse prognosis. Factors
      influencing stroke risk by subtype and subsequent prognosis are poorly described
      in the literature. STUDY DESIGN: Retrospective single-center cohort study.
      SETTING & PARTICIPANTS: 2,384 established maintenance hemodialysis patients at a
      single center from January 1, 2002, to June 1, 2009. PREDICTOR: Patient
      demographics, comorbid conditions. OUTCOMES: Incidence of acute stroke
      (International Classification of Diseases, 9th Revision codes 430, 431, 432.9,
      433.1, and 434.1 with evidence of compatible neuroimaging), patient survival.
      MEASUREMENTS: Cumulative patient survival, incidence of acute fatal and nonfatal
      stroke. RESULTS: 127 strokes occurred during 9,541 total patient-years of follow
      up. First (incident) stroke occurred at a rate of 14.9/1,000 patient years (95%
      CI, 12.2-17.9) with a predominance of ischemic compared with hemorrhagic subtypes
      (11.2 vs 3.7/1,000 patient-years). 54% of hemorrhagic strokes occurred in
      patients of South Asian ethnicity compared with ischemic strokes, which occurred
      predominantly in white patients (45% of events). Diabetes mellitus (HR, 1.92; 95%
      CI, 1.29-2.85; P = 0.001) and prior cerebrovascular disease (HR, 4.54; 95% CI,
      3.07-6.72; P < 0.001) were independently associated with incident cerebrovascular
      accident on multivariate analysis. Acute stroke was associated with worse patient
      survival (HR, 3.26; 95% CI, 2.47-4.30; P < 0.001) and overall 1-year mortality of
      24%, which was significantly worse in patients with hemorrhagic events (39% vs
      19% mortality for ischemic subtypes). Serum albumin level >3.5 g/L (HR, 0.38; 95%
      CI, 0.19-0.76; P = 0.007) and C-reactive protein level >3.0 mg/l (HR, 1.36; 95%
      CI, 1.12-1.64; P = 0.002) influenced survival after stroke on multivariate
      analysis. LIMITATIONS: Retrospective analysis of data cannot prove causality.
      CONCLUSIONS: The high incidence of stroke in hemodialysis patients is associated
      with high mortality, especially hemorrhagic subtypes. Strict management of
      hypertension, better appreciation of hemodialysis anticoagulation, and large
      scale interventional studies are urgently required to direct prevention and
      treatment of this significant disease.

PMID- 21944666
TI  - Progression of coronary artery calcification and thoracic aorta calcification in
      kidney transplant recipients.
AB  - BACKGROUND: Vascular calcification independently predicts cardiovascular disease,
      the major cause of death in kidney transplant recipients (KTRs). Longitudinal
      studies of vascular calcification in KTRs are few and small and have short follow
      up. We assessed the evolution of coronary artery (CAC) and thoracic aorta
      calcification and their determinants in a cohort of prevalent KTRs. STUDY DESIGN:
      Longitudinal. SETTING & PARTICIPANTS: The Agatston score of coronary arteries and
      thoracic aorta was measured by 16-slice spiral computed tomography in 281 KTRs.
      PREDICTORS: Demographic, clinical, and biochemical parameters were recorded
      simultaneously. OUTCOMES & MEASUREMENTS: The Agatston score was measured again
      3.5 or more years later. RESULTS: Repeated analyzable computed tomographic scans
      were available for 197 (70%) KTRs after 4.40 +/- 0.28 years; they were not
      available for the rest of patients because of death (n = 40), atrial fibrillation
      (n = 1), other arrhythmias (n = 4), refusal (n = 35), or technical problems
      precluding confident calcium scoring (n = 4). CAC and aorta calcification scores
      increased significantly (by a median of 11% and 4% per year, respectively) during
      follow-up. By multivariable linear regression, higher baseline CAC score, history
      of cardiovascular event, use of a statin, and lower 25-hydroxyvitamin D(3) level
      were independent determinants of CAC progression. Independent determinants of
      aorta calcification progression were higher baseline aorta calcification score,
      higher pulse pressure, use of a statin, older age, higher serum phosphate level,
      use of aspirin, and male sex. Significant regression of CAC or aorta
      calcification was not observed in this cohort. LIMITATIONS: Cohort of prevalent
      KTRs with potential survival bias; few patients with diabetes and nonwhites,
      limiting the generalizability of results. CONCLUSION: In contrast to previous
      small short-term studies, we show that vascular calcification progression is
      substantial within 4 years in prevalent KTRs and is associated with several
      traditional and nontraditional cardiovascular risk factors, some of which are
      modifiable.

PMID- 21944668
TI  - Integrating clinical perspectives into graduate education.

PMID- 21944669
TI  - Administering human adipose-derived mesenchymal stem cells to prevent and treat
      experimental arthritis.
AB  - Rheumatoid arthritis is a chronic autoimmune disease and affecting approximately
      1% of the population. Human adipose-derived mesenchymal stem cells (hASCs) were
      recently found to suppress effector T cell and inflammatory responses and, thus,
      to have beneficial effects in various autoimmune diseases. In this study, we
      examined whether hASCs could play a protective and/or therapeutic role in
      collagen-induced arthritis (CIA). We showed that hASCs both prevented and treated
      CIA by significantly reducing the incidence and severity of experimental
      arthritis. We further demonstrated that treatment with hASCs inhibited the
      production of various inflammatory mediators, decreased antigen-specific Th1/Th17
      cell expansion, and induced the production of anti-inflammatory cytokine
      interleukin-10. Moreover, hASCs could induce the generation of antigen-specific
      Treg cells with the capacity to suppress collagen-specific T cell responses.

PMID- 21944670
TI  - Cotransplantation of human embryonic stem cell-derived neural progenitors and
      schwann cells in a rat spinal cord contusion injury model elicits a distinct
      neurogenesis and functional recovery.
AB  - Cotransplantation of neural progenitors (NPs) with Schwann cells (SCs) might be a
      way to overcome low rate of neuronal differentiation of NPs following
      transplantation in spinal cord injury (SCI) and the improvement of locomotor
      recovery. In this study, we initially generated NPs from  human embryonic stem
      cells (hESCs) and investigated their potential for neuronal differentiation and
      functional recovery when cocultured with SCs in vitro and cotransplanted in a rat
      acute model of contused SCI. Cocultivation results revealed that the presence of
      SCs provided a consistent  status for hESC-NPs and recharged their neural
      differentiation toward a predominantly neuronal fate. Following transplantation,
      a significant functional recovery was observed in all engrafted groups (NPs, SCs,
      NPs + SCs) relative to the vehicle and control groups. We also observed that
      animals  receiving cotransplants established a better state as assessed with the
      BBB functional test. Immunohistofluorescence evaluation 5 weeks after
      transplantation showed invigorated neuronal differentiation and limited
      proliferation in the cotransplanted group when compared to the individual hESC-NP
      grafted  group. These findings have demonstrated that the cotransplantation of
      SCs with hESC-NPs could offer a synergistic effect, promoting neuronal
      differentiation and functional recovery.

PMID- 21944667
TI  - Comparison of measured GFR, serum creatinine, cystatin C, and beta-trace protein
      to predict ESRD in African Americans with hypertensive CKD.
AB  - BACKGROUND: Identification of persons with chronic kidney disease (CKD) who are
      at highest risk to progress to end-stage renal disease (ESRD) is necessary to
      reduce the burden of kidney failure. The relative utility of traditional markers
      of kidney function, including estimated glomerular filtration rate (eGFR) and
      serum creatinine level, and emerging markers of kidney function, including
      cystatin C and beta-trace protein (BTP) levels, to predict ESRD and mortality has
      yet to be established. STUDY DESIGN: Randomized clinical trial followed by an
      observational cohort study. SETTING & PARTICIPANTS: 865 African American
      individuals with hypertensive CKD enrolled in a clinical trial of 2 levels of
      blood pressure control and 3 different antihypertensive drugs as initial therapy
      and subsequently followed by an observational cohort study. PREDICTORS: Quintile
      of measured GFR (mGFR) by iothalamate clearance, serum creatinine, serum
      creatinine-based eGFR, cystatin C, and BTP values. OUTCOMES & MEASUREMENTS:
      Incidence of ESRD and mortality. RESULTS: 246 participants reached ESRD during a
      median follow-up of 102 months. The incidence rate of ESRD was higher with higher
      quintiles of each marker. The association between higher BTP level and ESRD was
      stronger than those for the other markers, including mGFR. All markers remained
      significantly associated with ESRD after adjustment for mGFR and relevant
      covariates (all P < 0.05), with BTP level retaining the strongest association (HR
      for highest vs lowest quintile, 5.7; 95% CI, 2.2-14.9). Associations with the
      combined end point of ESRD or mortality (n = 390) were weaker, but remained
      significant for cystatin C (P = 0.05) and BTP levels (P = 0.004). LIMITATIONS:
      The ability of these markers to predict ESRD and mortality in other racial and
      ethnic groups and in individuals with CKD due to other causes is unknown.
      CONCLUSIONS: Plasma BTP and cystatin C levels may be useful adjuncts to serum
      creatinine level and mGFR in evaluating risk of progression of kidney disease.

PMID- 21944671
TI  - Effect of 3-month repeated administration of miglitol on vascular endothelial
      function in patients with diabetes mellitus and coronary artery disease.
AB  - Repeated postprandial hyperglycemia may play an important role in the development
      of atherosclerosis by suppressing vascular endothelial function. Although
      miglitol suppresses the elevation of blood glucose levels shortly after a meal
      more than other alpha-glucosidase inhibitors, the effect of 3-month repeated
      administration of miglitol on endothelial dysfunction is unknown. Fifty patients
      with type 2 diabetes and coronary artery disease were enrolled in the present
      study. The patients were randomly divided into 2 groups, the first treated with
      miglitol and the second with voglibose for 3 months. Blood chemistry (lipid and
      blood glucose profiles, glycosylated hemoglobin, 1,5-anhydroglucitol, serum
      insulin levels, and C-reactive protein) and flow-mediated dilatation were
      measured at the beginning and end of the trial period. Patient characteristics
      and blood chemistry of the 2 groups were similar at the beginning of the trial.
      At the end of the trial, glycosylated hemoglobin decreased in the 2 groups, but
      the improvements in 1,5-anhydroglucitol in the miglitol group were significantly
      higher than in the voglibose group. Insulin resistance index, C-reactive protein,
      and percentage flow-mediated dilatation were also improved in the miglitol group
      but not in the voglibose group. In conclusion, 3-month repeated administration of
      miglitol improved vascular endothelial dysfunction by strongly suppressing
      postprandial hyperglycemia. Miglitol may have antiatherogenic effects in patients
      with type 2 diabetes and coronary artery disease.

PMID- 21944672
TI  - Relation between red blood cell omega-3 fatty acid index and bleeding during
      acute myocardial infarction.
AB  - Omega-3 fatty acids have multiple cardiovascular benefits but may also inhibit
      platelet aggregation and increase bleeding risk. If this platelet inhibition is
      clinically meaningful, patients with the highest omega-3 indexes (red blood cell
      eicosapentaenoic acid plus docosahexaenoic acid), which reflect long-term omega-3
      fatty acid intake, should be at the risk for bleeding. In this study, 1,523
      patients from 24 United States centers who had their omega-3 indexes assessed at
      the time of acute myocardial infarction were studied. The rates of serious
      bleeding (Thrombolysis In Myocardial Infarction [TIMI] major or minor) and mild
      to moderate bleeding (TIMI minimal) were identified in patients with low (<4%),
      intermediate (4% to 8%), and high (>8%) omega-3 indices. There were no
      differences in bleeding across omega-3 index categories. After multivariate
      adjustment, there remained no association between the omega-3 index and either
      serious (per 2% increase, relative risk 1.03, 95% confidence interval 0.90 to
      1.19) or mild to moderate bleeding (per 2% increase, relative risk 1.02, 95%
      confidence interval 0.85 to 1.23). In conclusion, no relation was found between
      the omega-3 index and bleeding in this large, multicenter cohort of patients with
      acute myocardial infarction, suggesting that concerns about bleeding should not
      preclude the use of omega-3 supplements or increased fish consumption when
      clinically indicated.

PMID- 21944673
TI  - Effect of repeated sauna treatment on exercise tolerance and endothelial function
      in patients with chronic heart failure.
AB  - Repeated sauna treatment, known as Waon therapy, has been shown to improve
      cardiac function as well as exercise tolerance in patients with chronic heart
      failure. However, the underlying mechanisms of this therapy regarding these
      improvements remain to be elucidated. Forty-one patients with chronic heart
      failure (mean age 68.3 +/- 13.5 years old) underwent Waon therapy 5 times a week
      for 3 weeks. Before and after treatment, a number of assessments were performed
      in all subjects: 6-minute walk test, echocardiography, determination of
      neurohumoral factors and number of circulating CD34(+) cells, and a flow-mediated
      dilation (FMD) test of endothelial function. Cardiopulmonary exercise testing was
      also performed in 20 patients. Waon therapy increased the left ventricular
      ejection fraction (from 30.4 +/- 12.6% to 32.5% +/- 12.8%, p = 0.023) and reduced
      plasma levels of norepinephrine (from 400 +/- 258 to 300 +/- 187 pg/ml, p =
      0.015) and brain natriuretic peptide (from 550 +/- 510 to 416 +/- 431 pg/ml, p =
      0.035). Waon therapy increased the 6-minute walk distance (from 337 +/- 120 to
      379 +/- 126 m, p <0.001) in association with an improvement in FMD (from 3.5 +/-
      2.3% to 5.5% +/- 2.7%, p <0.001) and an increase in the number of circulating
      CD34(+) cells (p = 0.025). Changes in 6-minute walk distance were correlated
      positively with those in the left ventricular ejection fraction and FMD and
      negatively with those in plasma levels of norepinephrine and brain natriuretic
      peptide levels. A multivariate analysis revealed that an increase in FMD was the
      only independent determinant of 6-minute walk distance improvement. Finally, Waon
      therapy significantly increased peak Vo(2), and this increase was also correlated
      with changes in FMD. In conclusion, repeated sauna therapy in patients with
      chronic heart failure improves exercise tolerance in association with improvement
      in endothelial function.

PMID- 21944674
TI  - Reference values of tricuspid annular peak systolic velocity in healthy pediatric
      patients, calculation of z score, and comparison to tricuspid annular plane
      systolic excursion.
AB  - The tricuspid annular peak systolic velocity (TAPSV) is an echocardiographic
      measurement assessing right ventricular systolic function in children and adults.
      We determined the growth-related changes of the TAPSV to establish the references
      values for the entire pediatric age group. A prospective study was conducted of a
      group of 860 healthy pediatric patients (age 1 day to 18 years; body surface area
      [BSA] 0.14 to 2.30 m(2)). We determined the effects of age, gender, and BSA on
      the TAPSV values. Stepwise linear multiple regression analysis was used to
      estimate the TAPSV from the age, BSA, and gender. A correlation of normal TAPSV
      with normal tricuspid annular plane systolic excursion values was performed. The
      TAPSV ranged from a mean of 7.2 cm/s (z score +/- 2: 4.8 to 9.5 cm/s) in the
      newborn to 14.3 cm/s (z score +/- 2: 10.6 to 18.6 cm/s) in the 18-year-old
      adolescent. The TAPSV values showed a positive correlation with age and BSA, with
      a nonlinear course. No significant difference was found in the TAPSV values
      according to gender. A significant correlation was found between the TAPSV and
      tricuspid annular plane systolic excursion values in our pediatric population. In
      conclusion, the z scores of the TAPSV values were calculated, and percentile
      charts were established to serve as reference data for patients with congenital
      heart disease.

PMID- 21944675
TI  - Effectiveness of a volunteer-delivered lifestyle modification program for
      reducing cardiovascular disease risk factors.
AB  - Lifestyle modification has been demonstrated to effectively reduce the risk
      factors associated with cardiovascular disease, but there is a perception that it
      is costly to administer and resource. The present study examined the results
      achieved by a 30-day lifestyle modification program (Coronary Health Improvement
      Project) delivered by volunteers in a community setting. Changes in selected
      biometric measures of 5,070 participants in the Coronary Health Improvement
      Project programs delivered throughout North America (January 2006 to October
      2009), were assessed. Overall, significant reductions (p < 0.001) were recorded
      in body mass (-3.2%), systolic and diastolic blood pressure (-4.9% and -5.3%,
      respectively), total cholesterol (-11.0%), low-density lipoprotein cholesterol (
      13.0%), triglycerides (-7.7%), and fasting plasma glucose (-6.1%). Stratification
      of the data revealed more dramatic responses in those presenting with the
      greatest risk factor levels. Those presenting with cholesterol levels >280 mg/dl
      recorded an average reduction of 19.8%. A mean decrease of 16.1% in low-density
      lipoprotein levels was observed among those who entered the program with a low
      density lipoprotein level >190 mg/dl. Individuals who presented with
      triglycerides >500 mg/dl recorded a mean reduction of 44.1%. The Framingham
      assessment forecast that approximately 70 cardiac events would be averted during
      the subsequent decade in the cohort because of the program. In conclusion,
      significant reductions in cardiovascular disease risk factors can be achieved in
      a 30-day lifestyle intervention delivered by volunteers, providing a cost
      effective mode of administering lifestyle medicine.

PMID- 21944676
TI  - Predictive value of plasma glucose level on admission for short and long term
      mortality in patients with ST-elevation myocardial infarction treated with
      primary percutaneous coronary intervention.
AB  - Published reports describe a strong association between plasma glucose levels on
      admission and mortality in patients who undergo primary percutaneous coronary
      intervention for ST-segment elevation myocardial infarction. The aim of this
      study was to assess the predictive value of admission glucose levels for early
      and late mortality. From 2005 to 2007, 1,646 patients underwent primary
      percutaneous coronary intervention for ST-segment elevation myocardial infarction
      and were stratified according to admission plasma glucose level in category 1
      (<7.8 mmol/L; n = 747), category 2 (7.8 to 11.0 mmol/L; n = 620), or category 3
      (>11 mmol/L; n = 279). Event rates were estimated using the Kaplan-Meier method.
      A landmark survival analysis to 3-year follow-up was performed, with a landmark
      set at 30 days. Time-extended Cox regression was used to assess the predictive
      value of admission glucose levels. Furthermore, a stratified analysis was
      performed for known diabetes mellitus status at admission. Thirty-day mortality
      was 2.4% in category 1, 6% in category 2, and 22% in category 3 (p <0.01). Three
      year mortality in 30-day survivors was 5.9% in category 1, 8.2% in category 2,
      and 7.1% in category 3 (p = 0.27). Glucose level on admission was a strong
      predictor of 30-day mortality: for every 1 mmol/L increase, the hazard increased
      by 14% (hazard ratio 1.14, 95% confidence interval 1.09 to 1.19, p <0.01) in
      patients without diabetes, by 12% (hazard ratio 1.12, 95% confidence interval
      1.05 to 1.19, p <0.01) in those with diabetes, and by 13% (hazard ratio 1.13, 95%
      confidence interval 1.09 to 1.17, p <0.01) in the total cohort. After 30 days,
      glucose level at admission lost its predictive value. In conclusion, in patients
      with and those without diabetes, glucose level at admission is an independent
      predictor of early but not late mortality.

PMID- 21944677
TI  - Usefulness of the admission electrocardiogram to predict long-term outcomes after
      non-ST-elevation acute coronary syndrome (from the FRISC II, ICTUS, and RITA-3
      [FIR] Trials).
AB  - The aim of this study was to evaluate the independent prognostic value of
      qualitative and quantitative admission electrocardiographic (ECG) analysis
      regarding long-term outcomes after non-ST-segment elevation acute coronary
      syndromes (NSTE-ACS). From the Fragmin and Fast Revascularization During
      Instability in Coronary Artery Disease (FRISC II), Invasive Versus Conservative
      Treatment in Unstable Coronary Syndromes (ICTUS), and Randomized Intervention
      Trial of Unstable Angina 3 (RITA-3) patient-pooled database, 5,420 patients with
      NSTE-ACS with qualitative ECG data, of whom 2,901 had quantitative data, were
      included in this analysis. The main outcome was 5-year cardiovascular death or
      myocardial infarction. Hazard ratios (HRs) were calculated with Cox regression
      models, and adjustments were made for established outcome predictors. The
      additional discriminative value was assessed with the category-less net
      reclassification improvement and integrated discrimination improvement indexes.
      In the 5,420 patients, the presence of ST-segment depression (>=1 mm; adjusted HR
      1.43, 95% confidence interval [CI] 1.25 to 1.63) and left bundle branch block
      (adjusted HR 1.64, 95% CI 1.18 to 2.28) were independently associated with long
      term cardiovascular death or myocardial infarction. Risk increases were short and
      long term. On quantitative ECG analysis, cumulative ST-segment depression (>=5
      mm; adjusted HR 1.34, 95% CI 1.05 to 1.70), the presence of left bundle branch
      block (adjusted HR 2.15, 95% CI 1.36 to 3.40) or >=6 leads with inverse T waves
      (adjusted HR 1.22, 95% CI 0.97 to 1.55) was independently associated with long
      term outcomes. No interaction was observed with treatment strategy. No
      improvements in net reclassification improvement and integrated discrimination
      improvement were observed after the addition of quantitative characteristics to a
      model including qualitative characteristics. In conclusion, in the FRISC II,
      ICTUS, and RITA-3 NSTE-ACS patient-pooled data set, admission ECG characteristics
      provided long-term prognostic value for cardiovascular death or myocardial
      infarction. Quantitative ECG characteristics provided no incremental
      discrimination compared to qualitative data.

PMID- 21944678
TI  - Type-selective benefits of medications in treatment of acute aortic dissection
      (from the International Registry of Acute Aortic Dissection [IRAD]).
AB  - The effects of medications on the outcome of aortic dissection remain poorly
      understood. We sought to address this by analyzing the International Registry of
      Acute Aortic Dissection (IRAD) global registry database. A total of 1,301
      patients with acute aortic dissection (722 with type A and 579 with type B) with
      information on their medications at discharge and followed for <=5 years were
      analyzed for the effects of the medications on mortality. The initial univariate
      analysis showed that use of beta blockers was associated with improved survival
      in all patients (p = 0.03), in patients with type A overall (p = 0.02), and in
      patients with type A who received surgery (p = 0.006). The analysis also showed
      that use of calcium channel blockers was associated with improved survival in
      patients with type B overall (p = 0.02) and in patients with type B receiving
      medical management (p = 0.03). Multivariate models also showed that the use of
      beta blockers was associated with improved survival in those with type A
      undergoing surgery (odds ratio 0.47, 95% confidence interval 0.25 to 0.90, p =
      0.02) and the use of calcium channel blockers was associated with improved
      survival in patients with type B medically treated patients (odds ratio 0.55, 95%
      confidence interval 0.35 to 0.88, p = 0.01). In conclusion, the present study
      showed that use of beta blockers was associated with improved outcome in all
      patients and in type A patients (overall as well as in those managed surgically).
      In contrast, use of calcium channel blockers was associated with improved
      survival selectively in those with type B (overall and in those treated
      medically). The use of angiotensin-converting enzyme inhibitors did not show
      association with mortality.

PMID- 21944679
TI  - Respiratory research in the critically ill pediatric patient: why is it so
      difficult?
AB  - Pediatric clinicians strive to base their management decisions on best available
      evidence. In the quantitative research paradigm, the highest level of evidence is
      derived from a conclusive randomized controlled clinical trial (RCT). Currently,
      there are few adequately powered RCTs to  support pediatric acute respiratory
      care, but this landscape is changing. We are all obligated to ensure the
      relevance of our research, to mentor junior investigators, and to support
      knowledge development in our field. This paper reviews the hurdles faced by
      clinical investigators in the field  of pediatric critical care and offers
      suggestions for future clinical studies.

PMID- 21944680
TI  - Management of acute lung injury: sharing data between adults and children.
AB  - As the basis for this paper, it must be acknowledged that children are not simply
      small adults. But this acknowledgment must go further: infants are not simply
      small adolescents. As data for pediatric mechanical ventilation, in general, and
      the management for pediatric acute lung injury,  more specifically, are very
      limited, the pediatric critical care clinician must closely assess the available
      adult data and evaluate its application for infants and children. Given the
      hurdles in studying pediatric acute lung injury and acute respiratory distress
      syndrome, clinicians involved  with the care of critically ill infants and
      children are left with extrapolation of data from the neonatal and adult
      populations, reliance on the limited available pediatric data, careful assessment
      of the applicable physiologic and pathophysiologic principles, and/or reliance on
      their own  experience and their colleagues' experience. Hopefully, with the
      collaboration of multicenter investigator networks, additional and definitive
      pediatric data may be on the horizon. In the meantime, sharing data between adult
      and pediatric populations seems to be an essential approach to the  management of
      critically ill patients.

PMID- 21944681
TI  - Neonatal noninvasive ventilation techniques: do we really need to intubate?
AB  - The current trend for supporting neonates with respiratory distress syndrome is
      nasal continuous positive airway pressure (CPAP). Nearly half of all neonates who
      are supported with CPAP will still develop respiratory failure that requires
      potentially injurious endotracheal intubation  and invasive ventilation. Thus,
      the role of any neonatal clinician is to minimize invasive ventilation whenever
      possible, to avoid the multitude of complications that can arise when using this
      form of therapy. Noninvasive ventilation (NIV) is a form of respiratory
      assistance that provides  greater respiratory support than does CPAP and may
      prevent intubation in a larger fraction of neonates who would otherwise fail
      CPAP. With the inception of nasal airway interfaces, clinicians have ushered in
      many different forms of NIV in neonates, often with very little experimental data
      to guide management. This review will explore in detail all of the different
      forms of neonatal NIV that are currently focused within an area of intense
      clinical investigation.

PMID- 21944682
TI  - Mechanical ventilation of the premature neonate.
AB  - Although the trend in the neonatal intensive care unit is to use noninvasive
      ventilation whenever possible, invasive ventilation is still often necessary for
      supporting pre-term neonates with lung disease. Many different ventilation modes
      and ventilation strategies are available to  assist with the optimization of
      mechanical ventilation and prevention of ventilator-induced lung injury. Patient
      triggered ventilation is favored over machine-triggered forms of invasive
      ventilation for improving gas exchange and patient-ventilator interaction.
      However, no studies have shown  that patient-triggered ventilation improves
      mortality or morbidity in premature neonates. A promising new form of patient
      triggered ventilation, neurally adjusted ventilatory assist (NAVA), was recently
      FDA approved for invasive and noninvasive ventilation. Clinical trials are
      underway to  evaluate outcomes in neonates who receive NAVA. New evidence
      suggests that volume-targeted ventilation modes (ie, volume control or pressure
      control with adaptive targeting) may provide better lung protection than
      traditional pressure control modes. Several volume-targeted modes that provide 
      accurate tidal volume delivery in the face of a large endotracheal tube leak were
      recently introduced to the clinical setting. There is ongoing debate about
      whether neonates should be managed invasively with high-frequency ventilation or
      conventional ventilation at birth. The majority of clinical  trials performed to
      date have compared high-frequency ventilation to pressure control modes. Future
      trials with premature neonates should compare high-frequency ventilation to
      conventional ventilation with volume-targeted modes. Over the last decade many
      new promising approaches to lung-protective  ventilation have evolved. The key to
      protecting the neonatal lung during mechanical ventilation is optimizing lung
      volume and limiting excessive lung expansion, by applying appropriate PEEP and
      using shorter inspiratory time, smaller tidal volume (4-6 mL/kg), and permissive
      hypercapnia.  This paper reviews new and established neonatal ventilation modes
      and strategies and evaluates their impact on neonatal outcomes.

PMID- 21944683
TI  - Advances in the management of pediatric pulmonary hypertension.
AB  - Pulmonary hypertension is a rare disease in neonates, infants, and children, and
      is associated with substantial morbidity and mortality. An adequate understanding
      of the controlling pathophysiologic mechanisms is lacking. Moreover, a minority
      of research is focused specifically on neonatal  and pediatric populations.
      Although therapeutic options have increased over the past several decades, they
      remain limited. In advanced pulmonary hypertension, progressive pulmonary
      vascular functional and structural changes ultimately cause increased pulmonary
      vascular impedance, right-ventricular  failure, and death. Management includes
      the prevention and/or treatment of active pulmonary vasoconstriction, the support
      of right-ventricle function, treatment of the underlying disease (if possible),
      and the promotion of regressive remodeling of structural pulmonary vascular
      changes. Most  currently available therapies augment or inhibit factors, or
      mediators of their downstream signaling cascades, that originate in the pulmonary
      vascular endothelium. These pathways include nitric-oxide/cyclic guanosine
      monophosphate (cGMP), prostacyclin, and endothelin-1. The ability to reverse 
      advanced structural changes remains an as yet unattained goal. This paper reviews
      the epidemiology, pathophysiology, current treatments, and emerging therapies
      related to neonatal and pediatric pulmonary hypertension.

PMID- 21944684
TI  - Inhaled medical gases: more to breathe than oxygen.
AB  - The mixture of oxygen and nitrogen is usually sufficient to achieve the
      therapeutic objective of supporting adequate gas exchange. Pediatric and neonatal
      patients have an assortment of physiologic conditions that may require adjunctive
      inhaled gases to treat the wide variety of diseases  seen in this heterogeneous
      population. Inhaled nitric oxide, helium oxygen mixtures, inhaled anesthetics,
      hypercarbic mixtures, hypoxic mixtures, inhaled carbon monoxide, and hydrogen
      sulfide have been used to alter physiology in an attempt to improve patient
      outcomes. Balancing the therapeutic  potential, possible adverse effects, and the
      complexity of the technical aspects of gas delivery, it is essential that
      clinicians thoroughly understand the application of medical gas therapy beyond
      the traditional nitrogen/oxygen mixture.

PMID- 21944685
TI  - Resuscitation in the delivery room: lung protection from the first breath.
AB  - Resuscitation of newborn infants occurs in approximately 10% of the more than 100
      million infants born annually worldwide. The techniques used during
      resuscitation, such as positive-pressure ventilation and supplemental oxygen, may
      revive many infants, but have the potential to harm  their lungs. In recent years
      increasing attention has been applied to providing lung protection from the first
      breath. This paper reviews the currently available medical evidence concerning
      modifying aspects of delivery room management that are thought to mitigate lung
      injury. These include:  F(IO(2)) < 1.0; early use of continuous positive airway
      pressure (CPAP) and PEEP; optimizing pressure and/or volume during ventilation;
      sustained inflations; need for and timing of surfactant therapy; and airway
      management of meconium-stained amniotic fluid. Although the  evidence against
      100% oxygen use is of low quality, it has been enough to alter the
      recommendations for oxygen use in the delivery room. It is suggested (not
      mandated) to use room air initially when resuscitating a term-gestation infant,
      and to use F(IO(2)) < 1.0 in premature  infants, with F(IO(2)) adjustments
      depending on oximetry values. Recent studies have not indicated better outcomes
      in premature infants in whom CPAP or PEEP is applied in the delivery room.
      Optimal peak ventilatory pressure and tidal volume have yet to be delineated.
      Although  an intriguing therapy, sustained inflations have not been shown to
      markedly improve outcomes. Prophylactic use of surfactant in small, premature
      infants remains the accepted standard. Immediate placement on CPAP after
      surfactant instillation has yet to demonstrate clear-cut advantages. Finally, 
      intrapartum oropharyngeal and nasopharyngeal suctioning of meconium-stained
      amniotic fluid does not improve outcomes in meconium-stained infants. Moreover,
      routine intubation and intratracheal suctioning of apparently vigorous meconium
      stained infants do not improve outcomes. In summary, although  multiple therapies
      are touted as protecting the lungs in the delivery room "from the first breath,"
      to date there are scant supportive data.

PMID- 21944686
TI  - The future of exogenous surfactant therapy.
AB  - Since the identification of surfactant deficiency as the putative cause of the
      infant respiratory distress syndrome (RDS) by Avery and Mead in 1959, our
      understanding of the role of pulmonary surfactant in respiratory physiology and
      the pathophysiology of acute lung injury (ALI) has  advanced substantially.
      Surfactant replacement has become routine for the prevention and treatment of
      infant RDS and other causes of neonatal lung injury. The role of surfactant in
      lung injury beyond the neonatal period, however, has proven more complex.
      Relative surfactant deficiency, dysfunction,  and inhibition all contribute to
      the disturbed physiology seen in ALI and acute respiratory distress syndrome
      (ARDS). Consequently, exogenous surfactant, while a plausible therapy, has proven
      to be less effective in ALI/ARDS than in RDS, where simple deficiency is
      causative. This failure may  relate to a number of factors, among them inadequacy
      of pharmaceutical surfactants, insufficient dosing or drug delivery, poor drug
      distribution, or simply an inability of the drug to substantially impact the
      underlying pathophysiology of ALI/ARDS. Both animal and human studies suggest
      that  direct types of ALI (eg, aspiration, pneumonia) may be more responsive to
      surfactant therapy than indirect lung injury (eg, sepsis, pancreatitis). Animal
      studies are needed, however, to further clarify aspects of drug composition,
      timing, delivery, and dosing before additional human trials  are pursued, as the
      results of human trials to date have been inconsistent and largely disappointing.
      Further study and perhaps the development of more robust pharmaceutical
      surfactants offer promise that exogenous surfactant will find a place in our
      armamentarium of treatment of ALI/ARDS  in the future.

PMID- 21944687
TI  - Asthma: 2015 and beyond.
AB  - Asthma is a multifactorial, chronic inflammatory disease of the airways. The
      knowledge that asthma is an inflammatory disorder has become a core fundamental
      in the definition of asthma. Asthma's chief features include a variable degree of
      air-flow obstruction and bronchial hyper-responsiveness,  in addition to the
      underlying chronic airways inflammation. This underlying chronic airway
      inflammation substantially contributes to airway hyper-responsiveness, air-flow
      limitation, respiratory symptoms, and disease chronicity. However, this
      underlying chronic airway inflammation has implications  for the diagnosis,
      management, and potential prevention of the disease. This review for the
      respiratory therapy community summarizes these developments as well as providing
      an update on asthma epidemiology, natural history, cause, and pathogenesis. This
      paper also provides an overview on appropriate  diagnostic and monitoring
      strategies for asthma, pharmacology, and newer therapies for the future as well
      as relevant management of acute and ambulatory asthma, and a brief review of
      educational approaches.

PMID- 21944688
TI  - Pediatric aerosol therapy: new devices and new drugs.
AB  - The lung and conducting airways are ideal portals for drug delivery. The airways
      are easily accessible by oral or nasal inhalation; the airway and alveolar
      surface is large, allowing for drug dispersion; and many drugs do not cross the
      airway-blood barrier, permitting the use of higher  topical drug doses for airway
      disease than would be practical with systemic administration. On the other hand,
      alveolar deposition of drugs allows rapid absorption into the pulmonary
      circulation and back to the left heart and systemic distribution, bypassing the
      intestinal tract and liver  inactivation. Recently, there has been a feast of new
      aerosol devices and drug formulations that promise the effective delivery of an
      amazing array of medications far beyond pressurized metered-dose inhalers and
      nebulizers and asthma medicines.

PMID- 21944689
TI  - Pediatric airway maintenance and clearance in the acute care setting: how to stay
      out of trouble.
AB  - Traditional airway maintenance and clearance therapy and principles of
      application are similar for neonates, children, and adults. Yet there are
      distinct differences in physiology and pathology between children and adults that
      limit the routine application of adult-derived airway-clearance  techniques in
      children. This paper focuses on airway-clearance techniques and airway
      maintenance in the pediatric patient with acute respiratory disease,
      specifically, those used in the hospital environment, prevailing lung
      characteristics that may arise during exacerbations, and the differences  in
      physiologic processes unique to infants and children. One of the staples of
      respiratory care has been chest physiotherapy and postural drainage. Many new
      airway clearance and maintenance techniques have evolved, but few have
      demonstrated true efficacy in the pediatric patient population.  Much of this is
      probably due to the limited ability to assess outcome and/or choose a proper
      disease-specific or age-specific modality. Airway-clearance techniques consume a
      substantial amount of time and equipment. Available disease-specific evidence of
      airway-clearance techniques and airway  maintenance will be discussed whenever
      possible. Unfortunately, more questions than answers remain.

PMID- 21944690
TI  - Extracorporeal life support: moving at the speed of light.
AB  - Extracorporeal life support (ECLS), or extracorporeal membrane oxygenation (ECMO)
      as it is also known, has been used to support over 45,000 patients to date.
      Overall survival is 62%. After many years of no change in equipment and
      technology, there has been a recent flurry of new pumps,  cannulas, and
      oxygenators available for ECLS use. While the impact of this new technology is
      not yet completely defined, initial results have found that these systems provide
      safe support with lower priming volumes and less bleeding complications. New
      cannulas are also available, some making  it easier for venovenous support in
      patients, from infants through adults. The reported success of ECLS in patients
      with H1N1 during the 2009-2010 epidemic and the improved survival of patients
      randomized to the ECMO arm of a recently completed adult study of respiratory
      failure have  also brought ECLS into the spotlight much more than other years.
      Whether these developments will usher in a new era of ECLS expansion to a wider
      range of patients will require close consideration and observation. Other areas
      that need to be further refined include anticoagulation management,  treatment of
      bleeding complications, learning to "nurse" patients in an awake state, such as
      is done in some European (and a few United States) centers, and
      neurodevelopmental outcome on a long-term basis.

PMID- 21944691
TI  - Disaster planning for pediatrics.
AB  - Natural and man-made disasters are inevitable and appear to be more common in the
      current age. Substantial time and effort have been invested and millions of
      dollars spent on disaster prevention and management. An important oversight in
      this planning has been the special needs of children.  The vulnerability of
      children and their physiologic characteristics place them at increased risk
      during a disaster. Importantly, reunification with family and assurance of safety
      in this vulnerable group is a priority. This paper addresses issues related to
      pediatric needs, the medical system's  shortcomings in caring for children, and
      recommendations for action.

PMID- 21944692
TI  - Neonatal and pediatric respiratory care: what does the future hold?
AB  - Neonatal and pediatric respiratory care continues to move forward at a truly
      impressive pace. Recent technologic advances and an increasing number of
      randomized clinical trials are leading to improved outcomes for neonates,
      infants, children, and adolescents with respiratory illness.  The goals of this
      47th Respiratory Care Journal Conference were to review pertinent recent advances
      in neonatal and pediatric respiratory care and, more importantly, to offer
      thoughts and perspectives for the future of our field. It is important to note
      that of the prior 46 Journal Conferences,  only 2 have been dedicated to neonatal
      and/or pediatric respiratory care topics. It is our hope that the publication of
      these proceedings will provide respiratory therapists, physicians, and other
      members of the clinical care team a foundation on which to ponder the future of
      neonatal and  pediatric respiratory care.

PMID- 21944693
TI  - Freshwater mudsnail (Potamopyrgus antipodarum) estrogen receptor: identification
      and expression analysis under exposure to (xeno-)hormones.
AB  - Molluscs are raising attention as ecotoxicological test organisms due to their
      high diversity and ecological importance. The ovoviviparous prosobranch gastropod
      Potamopyrgus antipodarum (freshwater mudsnail) responds very sensitively to
      xenobiotics and has therefore been proposed as OECD standard test organism.
      Endocrine disrupting chemicals influence the reproduction of P. antipodarum,
      which can be assessed by embryo numbers in the brood pouch. However, the
      knowledge about the endocrine system of P. antipodarum is rather limited. The aim
      of this study was to identify an estrogen receptor in the endocrine system of P.
      antipodarum and to investigate if this receptor is differentially expressed under
      exposure to (xeno-)hormones (17alpha-ethinylestradiol, bisphenol A and 17alpha
      methyltestosterone). The DNA-binding domain of the identified ER-like transcript
      has an amino acid identity of 92 percent compared to the ER of the gastropod
      Nucella lapillus (84 percent to human ERalpha) and 83 percent in the ligand
      binding domain (38 percent to human ERalpha). Furthermore, the P. antipodarum ER
      is transcriptionally regulated as shown by quantitative real-time PCRs of (xeno
      )hormone exposed snails. 17alpha-ethinylestradiol and bisphenol A exposure
      resulted in a transitory ER-mRNA increase while17alpha-methyltestosterone caused
      a transitory reduction of ER-mRNA. In addition the solvent dimethyl sulfoxide had
      also a modulating effect on the receptor.

PMID- 21944694
TI  - Swim performance and energy homeostasis in spottail shiner (Notropis hudsonius)
      collected downstream of a uranium mill.
AB  - The Key Lake uranium milling operation (Saskatchewan, Canada) releases complex
      effluent into the local watershed. The objective of the current study was to
      investigate whether fish from an effluent-receiving waterbody exhibited
      differences in swimming performance and energy homeostasis compared to fish from
      a local reference site. Juvenile spottail shiner (Notropis hudsonius) were
      collected from a lake downstream of the uranium mill, and compared to fish
      collected from a nearby reference lake. Critical swimming speed (U(crit); fatigue
      velocity), tail beat frequency, and tail amplitude did not differ significantly
      when comparing fish collected from the exposure lake and reference lake. Captured
      shiner used in swim tests were considered fatigued, and metabolic endpoints were
      compared between this group and non-fatigued fish, which were treated similarly
      but not subjected to swim tests. In both non-fatigued and fatigued shiner, liver
      glycogen was significantly greater in fish collected from the exposure lake
      compared to the reference lake. However, it is unclear if this effect, and others
      related to condition, were the result of contaminant exposure or other
      environmental factors. While there were no differences in plasma lactate,
      hematocrit or liver triglycerides in non-fatigued fish between sites, only
      fatigued reference fish had increased lactate and hematocrit and decreased
      triglycerides. In non-fatigued fish, plasma glucose did not significantly differ
      between sites, but significantly decreased after swimming only in fish from the
      exposure lake. In summary, shiner from the exposure site demonstrated similar
      swim endurance and possessed greater energy stores despite metabolic alterations
      compared to shiner from the reference site. Therefore, because fish collected
      downstream of the uranium mill operation had similar swimming ability as fish
      from the reference lake, U(crit) test results presented here may not reflect or
      be indicative of metabolic effects of complex effluent exposure.

PMID- 21944695
TI  - Pattern-based analysis of computer-interpretable guidelines: don't forget the
      context.

PMID- 21944696
TI  - Substrate stereoselectivity of mammalian D-aspartyl endopeptidase.
AB  - The formation and accumulation of D-aspartate residue (D-Asp) in proteins caused
      by oxidative stress leads to dysfunction and/or denaturation of proteins, and is
      consequently responsible for aging-related misfolding diseases such as cataracts,
      prion disease, and Alzheimer's disease. We sought to identify that an unknown
      protease selectively degrades the noxious D-Asp-containing protein, namely D
      aspartyl endopeptidase (DAEP), and finally purified it from the inner
      mitochondrial membrane of mouse liver. In order to analyze the substrate
      stereoselectivity of DAEP, we synthesized a peptide corresponding to 55-65 (Thr
      Val-Leu-Asp-Ser-Gly-Ile-Ser-Glu-Val-Arg) of human alphaA-crystallin and its
      corresponding diastereoisomers in which L-alpha-Asp was replaced with L-beta-, D
      alpha- or D-beta-Asp residue at position 58. Following incubation of that peptide
      with purified DAEP, it was only degraded at D-alpha-Asp(58), independent of ATP
      or NAD. This result indicates that DAEP stereoselectively recognizes and degrades
      its substrate at the internal D-alpha-Asp residue. DAEP therefore seems to
      physiologically serve as the quality control system against the noxious D-Asp
      containing protein in the long life span of mammals.

PMID- 21944697
TI  - Effects of lifestyle modification on coronary artery calcium progression and
      prognostic factors in coronary patients--3-year results of the randomized SAFE
      LIFE trial.
AB  - OBJECTIVE: Given the multimodal medical and interventional treatment options in
      coronary artery disease (CAD), the current value of intensified lifestyle
      modification remains unclear. No randomized studies have so far assessed the
      impact of lifestyle modification on coronary artery calcium (CAC). We examined
      the long-term effects of a one-year comprehensive lifestyle modification on risk
      factors and CAC by means of a randomized clinical trial. METHODS: 96 participants
      (age range 35-75 years, 22 women) of the SAFE-LIFE randomized trial in patients
      with established CAD completed 3-year follow-up. The active treatment was a one
      year lifestyle modification and stress reduction intervention (LG), while the
      control group received written advice only (AG). CAC (derived from electron beam
      tomography), blood lipids, heart rate, blood pressure, anginal symptoms and
      quality-of-life were assessed on entry and at 3-year follow-up. RESULTS:
      Lifestyle modification had no impact on change of CAC after three years (median
      progression factor [25th,75th percentile] 1.46 [1.16,2.19] in LG and 1.41
      [1.20,1.79] in AG; p=0.68), but led to reductions of blood pressure, heart rate
      and to dose-reductions in anti-ischemic medications as compared to AG. Multiple
      regression analysis indicated that in the pooled study population increase of CAC
      was related to psychosocial factors and heart rate. CONCLUSION: In the presence
      of modern treatments, complementary prescription of comprehensive lifestyle
      modification has no impact on CAC progression but sustainable benefit for blood
      pressure, heart rate and the need of anti-ischemic medication is demonstrated. A
      possible influence of stress reduction measures on CAC progression should be
      further evaluated.

PMID- 21944698
TI  - Estrogen-dependent activation of neutral cholesterol ester hydrolase underlying
      gender difference of atherogenesis in apoE-/- mice.
AB  - OBJECTIVE: Mechanisms underlying gender difference of atherogenesis were
      investigated focusing on direct effects of estrogen on the artery. METHODS:
      First, male and female apoE(-/-) mice were fed an atherogenic diet for 16 weeks
      from 10 weeks of age. Second, female apoE(-/-) mice were ovariectomized (ovx) or
      sham operated at 8 weeks of age, and 2-weeks afterwards, one-third of each ovx
      group received conjugated equine estrogens (CEE) (0, 2.5 or 5.0 MUg/day) for 16
      weeks. Atherosclerotic lesions were examined after experimental periods. To
      clarify anti-atherogenic effect of 17beta-estradiol (E2) on artery, neutral
      cholesteryl ester hydrolase (N-CEase) activity in aorta and peritoneal
      macrophages, and E2-treated J774A.1 cells were measured. RESULTS: First,
      atherosclerotic lesion in female mice was significantly less than male mice
      without any changes in serum lipids and lipoprotein profile. N-CEase activity in
      aorta and peritoneal macrophages in female mice was significantly higher than
      male mice. Second, atherosclerotic lesion in ovx-group was significantly greater
      than sham-group. CEE-replacement to ovx-group decreased atherosclerotic lesion in
      a dose-dependent manner. N-CEase activity in aorta and peritoneal macrophages was
      decreased in ovx-group compared to sham-group, and restored by CEE-replacement in
      macrophages. To study detailed mechanisms, J774A.1 cells were treated with E2. E2
      significantly increased N-CEase activity, and cAMP-dependent protein kinase (A
      kinase) type II activity and the protein in cytosol fraction without any changes
      of total protein of A-kinase type II. CONCLUSION: These results suggest that
      gender difference of atherogenesis is partly accounted for activation of N-CEase
      through estrogen-dependent translocation of A-kinase type II in macrophages.

PMID- 21944700
TI  - Refinement of the hereditary xerocytosis locus on chromosome 16q in a large
      Canadian kindred.
AB  - The hereditary stomatocytoses are a group of heterogeneous conditions associated
      with chronic red cell hemolysis for which the causative genetic mutations are not
      known. We investigated 137 members of a large Canadian kindred with phenotypic
      findings consistent with hereditary xerocytosis, one of the most common
      stomatocytosis syndromes. The objectives of this study were to characterize the
      clinical hallmarks of the hemolytic process, and to define the chromosomal region
      carrying the disease locus. The mode of inheritance was autosomal dominant.
      Affected family members had a well-compensated hemolysis, associated with an
      elevated MCHC, decreased osmotic fragility, decreased haptoglobin, and indirect
      hyperbilirubinemia. Cholelithiasis and progressive iron loading were common,
      despite normal hemoglobin levels. Quantitative erythrocyte morphologic evaluation
      revealed increased schistocytes, target cells, reticulocytes, and eccentrocytes
      in affected individuals; stomatocytes were not increased. Genetic linkage
      analysis confirmed the localization of the disease phenotype to chromosome 16q,
      and refined the candidate region to 16q24.2-16qter, a 2.4 million base pair
      interval containing 51 known or predicted genes.

PMID- 21944699
TI  - Plasma levels of sphingosine-1-phosphate and apolipoprotein M in patients with
      monogenic disorders of HDL metabolism.
AB  - BACKGROUND: Apolipoprotein M (apoM) has been identified as a specific sphingosine
      1-phosphate (S1P) binding protein of HDL. OBJECTIVES AND METHODS: To investigate
      the in vivo effects of disturbed apoM or HDL metabolism we quantified S1P and
      apoM in plasmas of wild-type, apoM-knock-out, and apoM transgenic mice as well as
      50 patients with seven different monogenic disorders of HDL metabolism and their
      51 unaffected relatives. RESULTS: Compared to wild type mice, S1P plasma levels
      in apoM knock-out and apoM transgenic mice were decreased by 30% and increased by
      270%, respectively. Compared to family controls, S1P and apoM levels in apoB
      depleted plasma were significantly decreased by in average 34% and 12%,
      respectively, in heterozygous carriers of mutations in APOA1, LCAT or ABCA1, and
      by 70% and 48%, respectively, in carriers of two defective alleles in LCAT or
      ABCA1. Heterozygous mutations in CETP, SCARB1, LIPC, or LIPG did not
      significantly affect S1P or apoM concentrations. Albumin-corrected molar S1P-to
      apoM ratios varied from 0.12 to 0.8 (median 0.3) and were not affected by any
      mutation. S1P levels in apoB-depleted plasma correlated significantly with HDL
      cholesterol and less so with apoM both if apoA-I plasma concentrations were below
      the median. CONCLUSION: In the context of previous data, our findings can be
      explained by the existence of a specific apoM and S1P containing HDL subclass
      which contains a considerable molar excess of apoM over S1P and is critically
      determined by apoA-I up to a threshold concentration around the median found in a
      Caucasian population.

PMID- 21944701
TI  - Preparation of nanocrystalline Fe 3-x LaxO4 ferrite and their adsorption
      capability for Congo red.
AB  - This investigation was to increase the adsorption capacity of magnetite for Congo
      red (CR) by adulterating a small quantity of La(3+) ions into it. The adsorption
      capability of nanocrystalline Fe(3-x)La(x)O(4) (x=0, 0.01, 0.05, 0.10) ferrite to
      remove CR from aqueous solution was evaluated carefully. Compared with undoped
      magnetite, the adsorption values were increased from 37.4 to 79.1 mg g(-1). The
      experimental results prove that it is effectual to increase the adsorption
      capacity of magnetite by doped La(3+) ions. Among the La(3+)-doped magnetite,
      Fe(2.95)La(0.05)O(4) nanoparticles exhibit the highest saturation magnetization
      and the maximum adsorption capability. The desorption ability of La(3+)-doped
      magnetite nanoparticles loaded by CR can reach 92% after the treatment of
      acetone. Furthermore, the Fe(3-x)La(x)O(4) nanoparticles exhibited a clearly
      ferromagnetic behavior under applied magnetic field, which allowed their high
      efficient magnetic separation from wastewater. It is found that high magnetism
      facilitates to improve their adsorption capacity for the similar products.

PMID- 21944702
TI  - Cadmium phytoextraction potential of different Alyssum species.
AB  - This work was planned for providing useful information about the possibility of
      using serpentine adapted plants for phytoextraction of cadmium, element scarcely
      represented in such metalliferous environment. To this aim, we investigated
      variation in cadmium tolerance, accumulation and translocation in three Alyssum
      plants with different phenotypes: Alyssum bertolonii, that is a serpentine
      endemic nickel hyperaccumulator, and two populations of Alyssum montanum, one
      adapted and one not adapted to serpentine soils. Plants were hydroponically
      cultivated in presence of increasing concentrations of CdSO(4) for two weeks. For
      the metal concentration used in the experiments, the three different Alyssum
      populations showed variation in cadmium tolerance, accumulation and content. The
      serpentine adapted population of A. montanum showed statistically higher cadmium
      tolerance and accumulation than A. bertolonii and the population of A. montanum
      not adapted to serpentine soil thus deserving to be investigated for
      phytoextraction purposes. Furthermore, as for the kinetic parameters of the
      cadmium uptake system, A. montanum serpentine population presented a low apparent
      K(m) value, suggesting a high affinity for this metal of its uptake system,
      whereas the V(max) values were not significantly different among the plants.
      Present data revealed metallicolous plants are also suitable for the
      phytoremediation of metals underrepresented in the environment of their initial
      origin. Nonetheless, field trials on real contaminated soils are essential.

PMID- 21944703
TI  - The influence of preparation method, nitrogen source, and post-treatment on the
      photocatalytic activity and stability of N-doped TiO2 nanopowder.
AB  - NH(3) plasma, N(2) plasma, and annealing in flowing NH(3) were used to prepare N
      doped TiO(2), respectively. XRD, UV-vis spectroscopy, N(2) adsorption, FT-IR,
      Zeta-potential measurement, and XP spectra were used to characterize the prepared
      TiO(2) samples. The nitridation procedure did not change the phase composition
      and particle sizes of TiO(2) samples, but extended its absorption edges to the
      visible light region. The photocatalytic activities were tested in the
      degradation of an aqueous solution of a reactive dyestuff, methylene blue, under
      visible light. The photocatalytic activity and stability of TiO(2) prepared by
      NH(3) plasma were much higher than that of samples prepared by other nitridation
      procedures. The visible light activity of the prepared N doped TiO(2) was
      improved by increasing the lattice-nitrogen content and decreasing adsorbed NH(3)
      on catalyst surface. The lattice-nitrogen stability of N-doped TiO(2) samples
      improved after HCl solution washing. The possible mechanism for the
      photocatalysis was proposed.

PMID- 21944704
TI  - Valorisation of electric arc furnace steel slag as raw material for low energy
      belite cements.
AB  - In this paper, the valorisation of electric arc furnace steel slag (EAFS) in the
      production of low energy belite cements is studied. Three types of clinkers were
      prepared with 0 wt.% (BC), 5 wt.% (BC5) and 10 wt.% (BC10) EAFS, respectively.
      The design of the raw mixes was based on the compositional indices lime
      saturation factor (LSF), alumina ratio (AR) and silica ratio (SR). The clinkering
      temperature was studied for the range 1280-1400 degrees C; firing was performed
      at 1380 degrees C based on the results regarding free lime and the evolution of
      microstructure. In order to activate the belite, clinkers were cooled fast by
      blown air and concurrent crushing. The results demonstrate that the
      microstructure of the produced clinkers is dominated by belite and alite
      crystals, with tricalcium aluminate and tetracalcium-alumino-ferrite present as
      micro-crystalline interstitial phases. The prepared cements presented low early
      strength development as expected for belite-rich compositions; however the 28-day
      results were 47.5 MPa, 46.6 MPa and 42.8 MPa for BC, BC5 and BC10, respectively.
      These values are comparable with OPC CEMI 32.5 N (32.5-52.5 MPa) according to EN
      197-1. A fast setting behaviour was also observed, particularly in the case of
      BC10, whereas soundness did not exceed 1mm.

PMID- 21944705
TI  - Water-soluble organo-building blocks of aminoclay as a soil-flushing agent for
      heavy metal contaminated soil.
AB  - We demonstrated that water-soluble aminopropyl magnesium functionalized
      phyllosilicate could be used as a soil-flushing agent for heavy metal
      contaminated soils. Soil flushing has been an attractive means to remediate heavy
      metal contamination because it is less disruptive to the soil environment after
      the treatment was performed. However, development of efficient and non-toxic soil
      flushing agents is still required. We have synthesized aminoclays with three
      different central metal ions such as magnesium, aluminum, and ferric ions and
      investigated applicability of aminoclays as soil flushing agents. Among them,
      magnesium (Mg)-centered aminoclay showed the smallest size distribution and
      superior water solubility, up to 100mg/mL. Mg aminoclay exhibited cadmium and
      lead binding capacity of 26.50 and 91.31 mg/g of Mg clay, respectively, at near
      neutral pH, but it showed negligible binding affinity to metals in acidic
      conditions. For soil flushing with Mg clay at neutral pH showed cadmium and lead
      were efficiently extracted from soils by Mg clay, suggesting strong binding
      ability of Mg clay with cadmium and lead. As the organic matter and clay
      compositions increased in the soil, the removal efficiency by Mg clay decreased
      and the operation time increased.

PMID- 21944706
TI  - Efficacy of liquid and foam decontamination technologies for chemical warfare
      agents on indoor surfaces.
AB  - Bench-scale testing was used to evaluate the efficacy of four decontamination
      formulations on typical indoor surfaces following exposure to the liquid chemical
      warfare agents sarin (GB), soman (GD), sulfur mustard (HD), and VX. Residual
      surface contamination on coupons was periodically measured for up to 24h after
      applying one of four selected decontamination technologies [0.5% bleach solution
      with trisodium phosphate, Allen Vanguard Surface Decontamination Foam (SDFTM),
      U.S. military Decon GreenTM, and Modec Inc. and EnviroFoam Technologies Sandia
      Decontamination Foam (DF-200)]. All decontamination technologies tested, except
      for the bleach solution, performed well on nonporous and nonpermeable glass and
      stainless-steel surfaces. However, chemical agent residual contamination
      typically remained on porous and permeable surfaces, especially for the more
      persistent agents, HD and VX. Solvent-based Decon GreenTM performed better than
      aqueous-based bleach or foams on polymeric surfaces, possibly because the solvent
      is able to penetrate the polymer matrix. Bleach and foams out-performed Decon
      Green for penetrating the highly polar concrete surface. Results suggest that the
      different characteristics needed for an ideal and universal decontamination
      technology may be incompatible in a single formulation and a strategy for
      decontaminating a complex facility will require a range of technologies.

PMID- 21944708
TI  - [Ergonomics of the workplace in radiology].
AB  - The replacement of conventional films and view boxes with digital images and
      computer monitors managed by PACS has clearly improved the diagnostic imaging
      workplace. The new setup has many advantages, including increased productivity
      brought about by decreased overall time required for image interpretation. On the
      other hand, the implementation of the digital workplace has increased the
      importance of factors like background lighting and the position of the chair,
      work table, mouse, keyboard, and monitor to prevent lesions that can disable the
      radiologist. The influence of these factors is often undervalued in the design
      and implementation of the radiological workplace. This article provides
      recommendations for the design of the radiological workplace based on ergonomics,
      which is the science that studies interactions among humans and other elements of
      a system.

PMID- 21944709
TI  - [Microwave ablation of a sarcoma lung metastasis in a patient with a pacemaker].
AB  - We present the case of a patient with a pacemaker and a sarcoma lung metastasis
      treated with microwave ablation. Although the treatment of tumours with microwave
      ablation is a successful and minimally invasive approach, there are concerns
      about the safety of this procedure for patients with implanted cardiac devices,
      such as a pacemaker. After careful planning between radiology and cardiology,
      microwave ablation was indicated in the patient since it is safer and shorter
      than the radiofrequency technique. The lesion was treated without complications.
      It is important to communicate the procedures performed, as well as any
      complications in order to formulate guidelines for the use of microwave ablation
      in patients with pacemakers. 

PMID- 21944710
TI  - [Complications after the use of a StarClose(r) vascular closure device for
      femoral punctures].
AB  - The StarClose((r)) arterial device (Abbot Vascular Devices, Abbot Laboratories,
      Redwood City, CA, USA) rapidly seals a femoral artery puncture by means of a
      nitinol clip in the adventitia of the artery. It is a safe and effective device,
      with advantages as regards manual compression, but is not free of complications.
      We present two cases with complications after using a StarClose((r)) vascular
      device. 

PMID- 21944711
TI  - [Diagnosis and management of adrenal incidentaloma].
AB  - The growing demand for imaging tests and the progressive aging of the population
      have led to a progressive increase in the detection of indeterminate adrenal
      lesions. Once an adrenal incidentaloma is detected, clinical and hormone tests
      together with a battery of imaging techniques (CT, MRI, PET/CT...) make it
      possible to determine the cause in most cases. In this article, we discuss the
      advantages and limitations of each technique. We show the imaging characteristics
      of the most common adrenal lesions and propose a diagnostic algorithm to enable
      their diagnosis.

PMID- 21944712
TI  - [Painful spine disorders: chance and opportunities with imaging techniques].

PMID- 21944713
TI  - [Incidental aneurysms and perimesencephalic subarachnoid haemorrhages].
AB  - A perimesencephalic subarachnoid hemorrhage refers to the presence of bleeding
      around the midbrain with a normal angiography, meeting the well established
      clinical criteria and radiological criteria. Unlike the aneurysmal subarachnoid
      hemorrhage, it has a good prognosis, the recovery in most cases being complete
      and satisfactory. On the other hand, between 2 and 5% of the population will
      develop an intracranial aneurysm in the course of their life, most of them
      asymptomatic, with the likelihood of finding an incidental aneurysm in patients
      who have suffered a perimesencephalic hemorrhage. The importance of a proper
      diagnosis governs the course to follow, being a challenge for vascular treatment
      teams who must analyse the findings in detail and individualize treatment
      decisions.

PMID- 21944714
TI  - [Pancreatic tail pseudoaneurysm: percutaneous treatment by thrombin injection].
AB  - Visceral artery pseudoaneurysms secondary to acute and/or chronic pancreatitis
      are a relatively common and potentially serious complication. Endovascular
      techniques are the most currently accepted techniques, given the higher morbidity
      mortality of surgery. The thrombosis of the pseudoaneurysm using an ultrasound
      guided percutaneous thrombin injection is emerging as a useful option in those
      cases in which endovascular embolisation is not possible. We present the case of
      a patient with a pseudoaneurysm of the transverse pancreatic artery secondary to
      chronic pancreatitis, and successfully treated by administering percutaneous
      thrombin. 

PMID- 21944715
TI  - The role of the PsbU subunit in the light sensitivity of PSII in the
      cyanobacterium Synechococcus 7942.
AB  - In the present study we investigated the role of the PsbU subunit in the electron
      transport characteristics and light sensitivity of the Photosystem II complex.
      The experiments were performed by using an earlier characterized PsbU-less mutant
      of the cyanobacterium Synechococcus PCC 7942, which has enhanced antioxidant
      capacity (Balint et al. FEBS Lett. 580 (2006) 2117-2122). Flash induced Chl
      fluorescence measurements in the presence and absence of the electron transport
      inhibitor DCMU showed that both the S(2)Q(A)(-) and the S(2)Q(B)(-) recombination
      is slowed down in the PsbU mutant relative to the WT strain. Thermoluminescence
      measurements confirmed the increased stability of the S(2)Q(A)(-) and S(2)Q(B)(-)
      charge pairs by showing an increased peak temperature of Q and B bands, which
      were measured in the presence and absence of DCMU, respectively. In addition, the
      intensity of the TL bands is also increased in the PsbU mutant (~1.7 times for
      the B band), as compared to the WT. The PsbU mutant shows enhanced loss of
      Photosystem II activity under exposure to high light intensity both in the
      absence and presence of the protein synthesis inhibitor lincomycin. It is
      concluded from the data that the lack of the PsbU subunit in Synechococcus PCC
      7942 affects the energetic stability of the S(2)Q(A)(-) and S(2)Q(B)(-) charge
      pairs by modifying both the PSII donor and acceptor side components. This effect
      is most likely caused by structural changes in the vicinity of the Mn cluster and
      in the inner part of the PSII complex, which are induced by the lack of the PsbU
      subunit from the lumenal part of the complex. The light sensitivity of
      Photosystem II in Synechococcus 7942 in the absence of the PsbU subunit is likely
      due to reactive oxygen species, which are produced as a consequence of disturbed
      donor side structure and/or due to the modified energetic properties of the
      primary radical pair.

PMID- 21944716
TI  - Rapid identification of bovine mastitis pathogens by high-resolution melt
      analysis of 16S rDNA sequences.
AB  - Accurate identification of mastitis pathogens is often compromised when using
      conventional culture-based methods. Here, we report a novel, rapid assay tested
      for speciation of bacterial mastitis pathogens using high-resolution melt
      analysis (HRMA) of 16S rDNA sequences. Real-time PCR amplification of 16S rRNA
      gene fragment, spanning the variable region V5 and V6 was performed with a
      resulting amplicon of 290bp. First, a library was generated of melt curves of 9
      common pathogens that are implicated in bovine mastitis. Six of the isolates,
      Escherichia coli, Streptococcus agalactiae, Klebsiella pneumoniae, Streptococcus
      uberis, Staphylococcus aureus and Mycoplasma bovis, were type strains while the
      other 3, Arcanobacterium pyogenes, Corynebacterium bovis and Streptococcus
      dysgalactiae, were bovine mastitis field isolates. Four of the type strains, E.
      coli, S. agalactiae, K. pneumoniae and S. aureus, were found to be of human
      origin, while the other 3 type strains were isolated from bovine infections.
      Secondly, the melt curves and corresponding amplicon sequences of A. pyogenes, E.
      coli, S. agalactiae, S. dysgalactiae, K. pneumoniae, S. uberis and S. aureus were
      compared with 10 bovine mastitis field isolates of each pathogen. Based on the
      distinct differences in melt curves and sequences between human and bovine
      isolates of E. coli and K. pneumoniae, it was deemed necessary to select a set of
      bovine strains for these pathogens to be used as reference strains in the HRMA.
      Next, the HRMA was validated by three interpreters analyzing the differential
      clustering pattern of melt curves of 60 bacterial cultures obtained from mastitis
      milk samples. The three test interpreters were blinded to the culture and
      sequencing results of the isolates. Overall accuracy of the validation assay was
      95% as there was difficulty in identifying the streptococci due to heterogeneity
      observed in the PCR amplicons of S. uberis. The present study revealed that broad
      range real-time PCR with HRMA can be used as a powerful, fast and low-cost tool
      for the differentiation of clinically important bacterial mastitis pathogens.

PMID- 21944717
TI  - The multidimensional relationship between early adult body weight and women's
      childbearing experiences.
AB  - This study has three primary goals that make an important contribution to the
      literature on body weight and childbearing experiences among United States'
      women. It sheds light on the physiological and social nature of this relationship
      by examining whether the consequences of early adult weight for lifetime
      childbearing are shaped by historical social context, women's social
      characteristics, and their ability to marry. We analyze data from two female
      cohorts who participated in the National Longitudinal Study of Youth (NLSY79).
      Cohort 1 entered early adulthood before the U.S. obesity prevalence increased.
      Cohort 2 entered early adulthood after the obesity prevalence increased. We find
      that early adult weight is negatively related to the childbearing trajectories
      and marital status of Cohort 1 but not Cohort 2. Failing to account for
      race/ethnicity and women's educational background as confounders masks some of
      these associations, which are evident for both White and Black women. Our results
      suggest that the health consequences of body weight do not fully drive its impact
      on childbearing. Rather, the lifetime fertility consequences of early adult
      weight are malleable, involve social processes, and are dependent on social
      context.

PMID- 21944718
TI  - How do obese individuals perceive and respond to the different types of obesity
      stigma that they encounter in their daily lives? A qualitative study.
AB  - Obesity stigma exists within many institutions and cultural settings. Most
      studies suggest that stigmatising experiences have a negative impact on
      individuals' health and social behaviours and outcomes. However, some studies
      indicate that obesity stigma can motivate individuals to lose weight. Limited
      research has examined weight-based stigma from the perspective of obese
      individuals, including their perceptions of, and responses to, the different
      types of weight-based stigma they face in their daily lives. This study advances
      knowledge about weight-based stigma by documenting how obese adults (mostly
      female) described the different types of obesity stigma that they faced, how they
      responded to this stigma, and how different types of stigma impact on health and
      social wellbeing. Semi-structured, qualitative interviews were conducted between
      April 2008 and March 2009 with a diverse sample of 141 obese Australian adults.
      Guided by Link and Phelan's (2006) categorisation of different types of
      discrimination, participants' experiences could be grouped into three distinct
      types of stigma: 1) Direct (e.g. being abused when using public transport); 2)
      Environmental (e.g. not being able to fit into seats on planes); and 3) Indirect
      (e.g. people staring at the contents of their supermarket trolley). Participants
      described that more subtle forms of stigma had the most impact on their health
      and social wellbeing. However, it was the interaction between direct,
      environmental and indirect stigma that created a barrier to participation in
      health-promoting activities. Participants rarely challenged stigma and often
      blamed themselves for stigmatising experiences. They also avoided situations
      where they perceived they would be stigmatised and constantly thought about how
      they could find a solution to their obesity.

PMID- 21944719
TI  - Dual role of mitofilin in mitochondrial membrane organization and protein
      biogenesis.
AB  - The mitochondrial inner membrane consists of two domains, inner boundary membrane
      and cristae membrane that are connected by crista junctions. Mitofilin/Fcj1 was
      reported to be involved in formation of crista junctions, however, different
      views exist on its function and possible partner proteins. We report that
      mitofilin plays a dual role. Mitofilin is part of a large inner membrane complex,
      and we identify five partner proteins as constituents of the mitochondrial inner
      membrane organizing system (MINOS) that is required for keeping cristae membranes
      connected to the inner boundary membrane. Additionally, mitofilin is coupled to
      the outer membrane and promotes protein import via the mitochondrial
      intermembrane space assembly pathway. Our findings indicate that mitofilin is a
      central component of MINOS and functions as a multifunctional regulator of
      mitochondrial architecture and protein biogenesis.

PMID- 21944721
TI  - Complementary targeting of liposomes to IL-1alpha and TNF-alpha activated
      endothelial cells via the transient expression of VCAM1 and E-selectin.
AB  - Inflammation is in part defined by the transient upregulation of cell adhesion
      molecules on the surface of endothelial cells (ECs) in response to cytokines. We
      hypothesized that liposomes with a complementary surface presentation of
      antibodies to the pattern of molecules on the EC surface may enhance targeting.
      We quantified the expression of vascular cell adhesion molecule-1 (VCAM1) and
      endothelial leukocyte cell adhesion molecule-1 (E-selectin) on ECs upon exposure
      to either tumor necrosis factor-alpha (TNF-alpha) or interleukin-1alpha (IL
      1alpha) as a function of time. Liposomes, composed of 95 mol% dioleoyl
      phosphatidylcholine (DOPC) and 5 mol% dodecanyl phosphatidylethanolamine (N-dod
      PE), were prepared by conjugating different molar ratios of antibodies against
      VCAM1 (aVCAM1) and E-selectin (aE-selectin). Increased binding was observed when
      immunoliposomes complemented the presentation of VCAM1:E-selectin expressed on
      TNF-alpha activated ECs. The 1:1 aVCAM1:aE-selectin liposomes had maximal binding
      at both 6 and 24 h on IL-1alpha activated ECs due to differences in molecular
      organization. The results demonstrate that liposomes targeting to inflamed
      endothelium may be optimized by exploiting the dynamic expression of VCAM1 and E
      selectin on the EC surface.

PMID- 21944720
TI  - Cyclin E constrains Cdk5 activity to regulate synaptic plasticity and memory
      formation.
AB  - Cyclin E is a component of the core cell cycle machinery, and it drives cell
      proliferation by regulating entry and progression of cells through the DNA
      synthesis phase. Cyclin E expression is normally restricted to proliferating
      cells. However, high levels of cyclin E are expressed in the adult brain. The
      function of cyclin E in quiescent, postmitotic nervous system remains unknown.
      Here we use a combination of in vivo quantitative proteomics and analyses of
      cyclin E knockout mice to demonstrate that in terminally differentiated neurons
      cyclin E forms complexes with Cdk5 and controls synapse function by restraining
      Cdk5 activity. Ablation of cyclin E led to a decreased number of synapses,
      reduced number and volume of dendritic spines, and resulted in impaired synaptic
      plasticity and memory formation in cyclin E-deficient animals. These results
      reveal a cell cycle-independent role for a core cell cycle protein, cyclin E, in
      synapse function and memory.

PMID- 21944722
TI  - The influence of ligand organization on the rate of uptake of gold nanoparticles
      by colorectal cancer cells.
AB  - We have explored the uptake of different hydrophilic mono- and dual-ligand gold
      nanoparticles in colorectal cancer cells in vitro and find that the rate of
      uptake is dependent on the structural organization of the ligands on the surface
      of the particles rather than their charge or chemical properties. Gold
      nanoparticles with 50%PEG-NH(2)/50% glucose are taken up eighteen fold faster
      than nanoparticles carrying only PEG-NH(2) or glucose. Glutathione-coated gold
      particles are by far the most efficiently internalized; however, glucose
      glutathione dual-ligand nanoparticles are taken up at a thirty fold reduced rate.
      We found furthermore that the rates are influenced by the cell density and
      concentration of glucose in the growth medium. Rather than being internalized
      through a conventional receptor-mediated mechanism the particles appear to be
      taken up by the cells via an energy-independent diffusion across the cell
      membrane through pre-existing pores or openings in the lipid bi-layer created by
      ligands on the gold nanoparticles.

PMID- 21944724
TI  - Cadherin-integrated liposomes with potential application in a drug delivery
      system.
AB  - N-cadherin (CDH2) proteins were reconstituted with liposomes using a baculovirus
      expression-liposome fusion method. CDH2 budded viruses were fused with giant
      liposomes containing dioleoylphophogycerol/dioleoylphosphatidylcholine
      (DOPG/DOPC) at pH 4.5 and the localization of CDH2 on the liposome membrane was
      observed by confocal laser scanning microscopy. CDH2 liposomes showed Ca(2+)
      dependent association. CDH2-mediated association/dissociation in CDH2 liposomes
      was specific to Ca(2+) and reversible. CDH2-expressing LN-229 cells (human
      glioblastoma cell) adhered to CDH2 liposomes and small CDH2 liposomes (diameter
      approximately 150 nm), in particular, were internalized by endocytosis and partly
      escaped endosomes. Cadherin-containing liposomes show high potential as a new
      cell-specific proteoliposome. The baculovirus expression-liposome fusion method
      is useful as a new enabling technology for biomedical applications of functional
      proteoliposomes.

PMID- 21944723
TI  - The potential for salmon fibrin and thrombin to mitigate pain subsequent to
      cervical nerve root injury.
AB  - Nerve root compression is a common cause of radiculopathy and induces persistent
      pain. Mammalian fibrin is used clinically as a coagulant but presents a variety
      of risks. Fish fibrin is a potential biomaterial for neural injury treatment
      because it promotes neurite outgrowth, is non-toxic, and clots readily at lower
      temperatures. This study administered salmon fibrin and thrombin following nerve
      root compression and measured behavioral sensitivity and glial activation in a
      rat pain model. Fibrin and thrombin each significantly reduced mechanical
      allodynia compared to injury alone (p < 0.02). Painful compression with fibrin
      exhibited allodynia that was not different from sham for any day using
      stimulation by a 2 g filament; allodynia was only significantly different (p <
      0.043) from sham using the 4 g filament on days 1 and 3. By day 5, responses for
      fibrin treatment decreased to sham levels. Allodynia following compression with
      thrombin treatment were unchanged from sham at any time point. Macrophage
      infiltration at the nerve root and spinal microglial activation were only mildly
      modified by salmon treatments. Spinal astrocytic expression decreased
      significantly with fibrin (p < 0.0001) but was unchanged from injury responses
      for thrombin treatment. Results suggest that salmon fibrin and thrombin may be
      suitable biomaterials to mitigate pain.

PMID- 21944725
TI  - Design of interior-functionalized fully acetylated dendrimers for anticancer drug
      delivery.
AB  - In this study, dendrimers was synthesized by introducing functional groups into
      the interior pockets of fully acetylated dendrimers. NMR techniques including
      COSY and 2D-NOESY revealed the molecular structures of the synthesized dendrimers
      and the encapsulation of guest molecule such as methotrexate within their
      interior pockets. The synthesized polymeric nanocarriers showed much lower
      cytotoxicity on two cell lines than cationic dendrimers, and exhibited better
      performance than fully acetylated dendrimers in the sustained release of
      methotrexate. The results provided a new strategy in the design of non-toxic
      dendrimers with high performance in the delivery of anti-cancer drugs for
      clinical applications.

PMID- 21944726
TI  - How r u?

PMID- 21944727
TI  - It's a beautiful day to be an optometrist!

PMID- 21944729
TI  - Letter to the editor.

PMID- 21944730
TI  - Case report: the correction of a high magnitude of astigmatism with laser
      assisted in situ keratomileusis.
AB  - BACKGROUND: Laser-assisted in situ keratomileusis (LASIK) has undergone several
      evolutions since it was first approved by the U.S. Food and Drug Administration.
      Currently, excimer lasers are approved by the U.S. Food and Drug Administration
      to treat refractive errors with a standard ablation profile, a wavefront
      optimized ablation profile, or a wavefront-guided ablation profile. Wavefront
      optimized ablation profiles provide a simple method to precompensate for the
      expected fourth-order spherical aberration and higher-order astigmatism in the
      average eye. CASE REPORT: We report a case of a 39-year-old white man, with a
      high magnitude of mixed astigmatism in the right and left eyes, who was seeking
      refractive surgical options because he was unable to tolerate contact lenses. The
      patient underwent bilateral wavefront-optimized LASIK to correct his high degree
      of astigmatism. Wavefront-guided ablation, as in this patient, can not always be
      performed because the parameters are not within the allowable treatment profile.
      Four months after the primary LASIK treatment, the patient underwent a bilateral
      wavefront-optimized LASIK enhancement for residual astigmatism. CONCLUSION: This
      case focuses on the utilization of a wavefront-optimized LASIK treatment profile
      to eliminate a high magnitude of astigmatic refractive error without inducing
      higher-order aberrations. Wavefront-guided treatments are not required in most
      cases but should be considered if the magnitude of preoperative root-mean-square
      higher-order aberrations is greater than 0.35 MUm. Wavefront-optimized aspheric
      corneal ablations attempt to avoid reducing the prolate eccentricity of the
      average cornea, and optimized treatments have shown improved visual outcomes
      compared with conventional LASIK treatments. A thorough knowledge of refractive
      surgery is important for any treating eye care practitioner to provide patients
      with the full range of options to correct all types of refractive errors.

PMID- 21944731
TI  - [In favour of one-stage surgical treatment of urinary incontinence associated
      with prolapse].

PMID- 21944732
TI  - Influence of dietary ingredients on in vitro inflammatory response of intestinal
      porcine epithelial cells challenged by an enterotoxigenic Escherichia coli (K88).
AB  - Enterotoxigenic Escherichia coli (ETEC) K88 is the main bacterial cause of
      diarrhea in piglets around weaning and the adhesion of ETEC to the intestinal
      mucosa is a prerequisite step for its colonization. In this study, the adhesion
      of a fimbriated ETEC and a non-fimbriated E. coli (NFEC) to the intestinal cells
      and the activation of the innate immune system were evaluated using a porcine
      intestinal epithelial cell line (IPEC-J2). The impact of several feedstuffs
      (wheat bran (WB); casein glycomacropeptide (CGMP); mannan-oligosaccharides (MOS);
      locust bean extract (LB) and Aspergillus oryzae fermentation extract (AO)) on
      ETEC attachment and the inflammatory response were also studied. The gene
      expression of TLR-4; TLR-5; IL-1beta; IL-8; IL-10 and TNF-alpha were quantified
      using Cyclophilin-A, as a reference gene, and related to a non-challenged
      treatment. The fimbriated strain was markedly better than the non-fimbriated
      strain at adherence to intestinal cells and inducing an inflammatory response.
      All the feedstuffs studied were able to reduce the adhesion of ETEC, with the
      greatest decrease with CGMP or MOS at highest concentration. Regarding the
      inflammatory response, the highest dose of WB promoted the lowest relative
      expression of cytokines and chemokines. All tested feedstuffs were able to reduce
      the adhesion of ETEC to IPEC-J2 and interfere on the innate inflammatory
      response; however WB should be further studied according to the beneficial
      results on the intestinal inflammatory process evidenced in this study.

PMID- 21944733
TI  - Porcine intestinal epithelial responses to Campylobacter infection.
AB  - Campylobacter infection is estimated to cause diarrhoea in 1% of the population
      of developed countries every year, but our understanding of this disease has been
      hampered by a lack of a suitable animal model. Colostrum-deprived piglets have
      been suggested as models since they produce similar clinical signs to humans when
      infected but little information currently exists regarding the response of this
      species to Campylobacter at cellular and molecular level. This study shows that
      intestinal epithelial cells from both species respond in a similar manner to
      Campylobacter infection regarding invasion, induction of innate immune response
      and effect on barrier function.

PMID- 21944734
TI  - Impact of gradient timing error on the tissue sodium concentration bioscale
      measured using flexible twisted projection imaging.
AB  - The rapid biexponential transverse relaxation of the sodium MR signal from brain
      tissue requires efficient k-space sampling for quantitative imaging in a time
      that is acceptable for human subjects. The flexible twisted projection imaging
      (flexTPI) sequence has been shown to be suitable for quantitative sodium imaging
      with an ultra-short echo time to minimize signal loss. The fidelity of the k
      space center location is affected by the readout gradient timing errors on the
      three physical axes, which is known to cause image distortion for projection
      based acquisitions. This study investigated the impact of these timing errors on
      the voxel-wise accuracy of the tissue sodium concentration (TSC) bioscale
      measured with the flexTPI sequence. Our simulations show greater than 20%
      spatially varying quantification errors when the gradient timing errors are
      larger than 10 MUs on all three axes. The quantification is more tolerant of
      gradient timing errors on the Z-axis. An existing method was used to measure the
      gradient timing errors with <1 MUs error. The gradient timing error measurement
      is shown to be RF coil dependent, and timing error differences of up to ~16 MUs
      have been observed between different RF coils used on the same scanner. The
      measured timing errors can be corrected prospectively or retrospectively to
      obtain accurate TSC values.

PMID- 21944735
TI  - Investigating the intermediates in the reaction of ribonucleoside triphosphate
      reductase from Lactobacillus leichmannii: An application of HF EPR-RFQ
      technology.
AB  - In this investigation high-frequency electron paramagnetic resonance spectroscopy
      (HFEPR) in conjunction with innovative rapid freeze-quench (RFQ) technology is
      employed to study the exchange-coupled thiyl radical-cob(II)alamin system in
      ribonucleotide reductase from a prokaryote Lactobacillus leichmannii. The size of
      the exchange coupling (Jex) and the values of the thiyl radical g tensor are
      refined, while confirming the previously determined (Gerfen et al. (1996) [20])
      distance between the paramagnets. Conclusions relevant to ribonucleotide
      reductase catalysis and the architecture of the active site are presented. A key
      part of this work has been the development of a unique RFQ apparatus for the
      preparation of millisecond quench time RFQ samples which can be packed into small
      (0.5 mm ID) sample tubes used for CW and pulsed HFEPR--lack of this ability has
      heretofore precluded such studies. The technology is compatible with a broad
      range of spectroscopic techniques and can be readily adopted by other
      laboratories.

PMID- 21944736
TI  - Surgical results in patients with pulmonary atresia-major aortopulmonary
      collaterals in association with total anomalous pulmonary venous connection.
AB  - BACKGROUND: Pulmonary atresia and major aortopulmonary collaterals (PA/MAPCAs) is
      a complex form of congenital heart disease. One to two percent of patients with
      PA/MAPCAs will also have total anomalous pulmonary venous connection (TAPVC).
      This study summarizes our surgical experience with this rare combination of life
      threatening congenital heart defects. METHODS: A retrospective review was
      performed to identify patients who had surgery for PA/MAPCAs in association with
      TAPVC. From November 2001 to March 2011, 9 patients presented with this
      combination of defects. Eight of the 9 patients had heterotaxy with an unbalanced
      atrioventricular canal and functional single ventricle. The ninth patient had
      double outlet right ventricle (two ventricles). Timing of surgical intervention
      was typically predicated on the degree of pulmonary venous obstruction. The
      median age at surgery was 14 days. All nine patients had surgical correction of
      TAPVC, unifocalization of MAPCA's into a central confluence, and placement of a
      shunt. RESULTS: There was one early mortality (< 30 days) and two late
      mortalities. For the 6 survivors, 5 have subsequently undergone a bidirectional
      Glenn procedure, and 3 had completion of their Fontan. Two patients are currently
      at the bidirectional Glenn stage; one is a good candidate for Fontan completion
      while the other is not suitable. The sixth patient is awaiting further
      assessment. CONCLUSIONS: The PA/MAPCAs, in association with TAPVC, is a
      challenging combination of defects. The data suggest that the combination of
      PA/MAPCAs and TAPVC can be undertaken with a reasonable midterm prognosis.

PMID- 21944737
TI  - Quality of life after collis gastroplasty for short esophagus in patients with
      paraesophageal hernia.
AB  - BACKGROUND: Collis gastroplasty is an important component of laparoscopic giant
      paraesophageal hernia (GPEH) repair in patients with persistent shortened
      esophagus after aggressive laparoscopic mobilization. Concerns remain, however,
      regarding symptomatic outcomes compared with fundoplication alone. This study
      assessed the impact of Collis gastroplasty on quality of life after laparoscopic
      GPEH repair. METHODS: We performed 795 nonemergent laparoscopic GPEH repairs with
      fundoplication (with Collis, n = 454; fundoplication alone, n = 341).
      Radiographic follow-up and symptom assessment were obtained a median 22 months
      and 20 months, respectively, after fundoplication alone and 36 and 33 months,
      respectively, after Collis (p < 0.001). Radiographic recurrence, reoperation for
      recurrent hernia or intolerable symptoms, overall symptom improvement, and
      quality of life were examined. RESULTS: Compared with fundoplication alone,
      Collis patients had significantly larger GPEH (p = 0.027) and fewer comorbidities
      (p = 0.002). Radiographic recurrences were similar (p = 0.353). Symptom
      improvement was significant for both (p < 0.001), although Collis was associated
      with better pain resolution (p < 0.001) and less gas bloat (p = 0.003). Quality
      of life was good to excellent in 88% (90% Collis versus 86% fundoplication alone,
      p = 0.17). CONCLUSIONS: Symptomatic outcomes after laparoscopic fundoplication
      with Collis gastroplasty are excellent and comparable with those of
      fundoplication alone. These results confirm that utilization of Collis
      gastroplasty, based on intraoperative assessment for shortened esophagus, is not
      detrimental to the overall outcome or quality of life associated with the
      laparoscopic approach to GPEH. Collis gastroplasty is recommended as an important
      procedure in the surgeon's armamentarium for laparoscopic repair of GPEH.

PMID- 21944738
TI  - Comparison of A1C, fasting and 2-h post-load plasma glucose criteria to diagnose
      diabetes in Italian Caucasians.
AB  - BACKGROUND AND AIMS: The American Diabetes Association (ADA) has revised criteria
      for diagnosis of type 2 diabetes recommending an A1C cut point of >=6.5% in
      addition to criteria based on glucose levels. We compared A1C, fasting plasma
      glucose (FPG) or 2-h post-challenge glucose (2-hPG) criteria for the diagnosis of
      diabetes in a cohort of Italian Caucasians. METHODS AND RESULTS: A total of 1019
      individuals without known diabetes completed an oral glucose tolerance test
      (OGTT) and had A1C measured. Moderate agreement existed for A1C and FPG criteria
      for diagnosis of type 2 diabetes (kappa coefficient = 0.522), with 85.5% of
      individuals classified as not having diabetes by both A1C and FPG criteria, and
      5.8% classified as having diabetes by both A1C and FPG criteria. Discordant
      classifications occurred for 5.5% of individuals who had an A1C >= 6.5% and FPG
      <126 mg dl(-1), and for 3.2% who had an A1C <6.5% and FPG >=126 mg dl(-1). Modest
      agreement existed for A1C and 2-hPG criteria for diagnosis of type 2 diabetes
      (kappa coefficient = 0.427), with 81.8% of individuals classified as not having
      diabetes by both A1C and 2-hPG criteria, and 6.0% classified as having diabetes
      by both A1C and 2-hPG criteria. The area under the receiver operating
      characteristic curve of A1C for identifying subjects with diabetes according to
      FPG or 2-hPG criteria was 0.856 and 0.794, respectively. Modest agreement existed
      for A1C and FPG and/or 2-hPG criteria for diagnosis of type 2 diabetes (kappa
      coefficient = 0.446). CONCLUSIONS: A1C >= 6.5% demonstrates a moderate agreement
      with fasting glucose and 2-hPG for diagnosing diabetes among adult Italian
      Caucasians subjects.

PMID- 21944739
TI  - Second-line therapy for refractory renal-cell carcinoma.
AB  - In the last 5 years inhibitors of the VEGF/VEGFR and mTOR pathways have
      dramatically changed the therapeutic approach to metastatic renal cancer.
      Randomized controlled trials have shown that six targeted agents--sorafenib,
      sunitinib, temsirolimus, bevacizumab, everolimus and pazopanib--are able to
      improve patient outcome. Even if the choice of drug for first-line therapy is
      quite well defined, to date it is not easy to characterize and evaluate the
      efficacy of new therapies in second-line treatment. It is not clear whether,
      after first-line therapy with a VEGF/VEGFR inhibitor, use of mTOR or a second TKI
      inhibitor should be recommended. In this review we report on current evidence
      supporting the use of targeted agents in second-line therapy. Therefore we try to
      combine current clinical results with a practical clinical approach, with the
      goal of evaluating the best clinical decision for different clinical situations.

PMID- 21944740
TI  - Evolvement of the treatment paradigm for metastatic colon cancer. From
      chemotherapy to targeted therapy.
AB  - Colorectal Cancer is the second most common cancer in incidence and mortality in
      the United States. In spite of current screening strategies 1 out of 5 patients
      still presents with metastatic disease. During the last 10-15 years there has
      been significant increase in the availability of chemotherapy options for this
      disease. The recent introduction of molecular markers to the treatment algorithm
      allows oncologists to tailor treatments for each particular patient. In the
      following article we give an overview of the landmark publications that led to
      our current standards and we give our view on particular situations in which the
      available evidence is not so helpful in making therapeutic decisions.

PMID- 21944741
TI  - Imaging cancer's blood supply.

PMID- 21944742
TI  - Bypassing GPCRs with chemical dimerizers.

PMID- 21944743
TI  - Coq6 hydroxylase: unmasked and bypassed.

PMID- 21944744
TI  - PDZ dimerization brings proteins together.

PMID- 21944745
TI  - Chemical activators of ClpP: turning Jekyll into Hyde.

PMID- 21944746
TI  - Acyl-CoA subunit selectivity in the pikromycin polyketide synthase PikAIV: steady
      state kinetics and active-site occupancy analysis by FTICR-MS.
AB  - Polyketide natural products generated by type I modular polyketide synthases
      (PKSs) are vital components in our drug repertoire. To reprogram these
      biosynthetic assembly lines, we must first understand the steps that occur within
      the modular "black boxes." Herein, key steps of acyl-CoA extender unit selection
      are explored by in vitro biochemical analysis of the PikAIV PKS model system. Two
      complementary approaches are employed: a fluorescent-probe assay for steady-state
      kinetic analysis, and Fourier Transform Ion Cyclotron Resonance-mass spectrometry
      (FTICR-MS) to monitor active-site occupancy. Findings from five enzyme variants
      and four model substrates have enabled a model to be proposed involving catalysis
      based upon acyl-CoA substrate loading followed by differential rates of
      hydrolysis. These efforts suggest a strategy for future pathway engineering
      efforts using unnatural extender units with slow rates of hydrolytic off-loading
      from the acyltransferase domain.

PMID- 21944747
TI  - Secretory protein profiling reveals TNF-alpha inactivation by selective and
      promiscuous Sec61 modulators.
AB  - Cotransins are cyclic heptadepsipeptides that bind the Sec61 translocon to
      inhibit cotranslational translocation of a subset of secreted and type I
      transmembrane proteins. The few known cotransin-sensitive substrates are all
      targeted to the translocon by a cleavable signal sequence, previously shown to be
      a critical determinant of cotransin sensitivity. By profiling two cotransin
      variants against a panel of secreted and transmembrane proteins, we demonstrate
      that cotransin side-chain differences profoundly affect substrate selectivity.
      Among the most sensitive substrates we identified is the proinflammatory cytokine
      tumor necrosis factor alpha (TNF-alpha). Like all type II transmembrane proteins,
      TNF-alpha is targeted to the translocon by its membrane-spanning domain,
      indicating that a cleavable signal sequence is not strictly required for
      cotransin sensitivity. Our results thus reveal an unanticipated breadth of
      translocon substrates whose expression is inhibited by Sec61 modulators.

PMID- 21944748
TI  - Drug repositioning and pharmacophore identification in the discovery of hookworm
      MIF inhibitors.
AB  - The screening of bioactive compound libraries can be an effective approach for
      repositioning FDA-approved drugs or discovering new pharmacophores. Hookworms are
      blood-feeding, intestinal nematode parasites that infect up to 600 million people
      worldwide. Vaccination with recombinant Ancylostoma ceylanicum macrophage
      migration inhibitory factor (rAceMIF) provided partial protection from disease,
      thus establishing a "proof-of-concept" for targeting AceMIF to prevent or treat
      infection. A high-throughput screen (HTS) against rAceMIF identified six AceMIF
      specific inhibitors. A nonsteroidal anti-inflammatory drug (NSAID), sodium
      meclofenamate, could be tested in an animal model to assess the therapeutic
      efficacy in treating hookworm disease. Furosemide, an FDA-approved diuretic,
      exhibited submicromolar inhibition of rAceMIF tautomerase activity. Structure
      activity relationships of a pharmacophore based on furosemide included one analog
      that binds similarly to the active site, yet does not inhibit the Na-K-Cl
      symporter (NKCC1) responsible for diuretic activity.

PMID- 21944749
TI  - Dihydrophenylalanine: a prephenate-derived Photorhabdus luminescens antibiotic
      and intermediate in dihydrostilbene biosynthesis.
AB  - 2,5-Dihydrophenylalanine (H(2)Phe) is a multipotent nonproteinogenic amino acid
      produced by various Actinobacteria and Gammaproteobacteria. Although the
      metabolite was discovered over 40 years ago, details of its biosynthesis have
      remained largely unknown. We show here that L-H(2)Phe is a secreted metabolite in
      Photorhabdus luminescens cultures and a precursor of a recently described 2,5
      dihydrostilbene. Bioinformatic analysis suggested a candidate gene cluster for
      the processing of prephenate to H(2)Phe, and gene knockouts validated that three
      adjacent genes plu3042-3044 were required for H(2)Phe production. Biochemical
      experiments validated Plu3043 as a nonaromatizing prephenate decarboxylase
      generating an endocyclic dihydro-hydroxyphenylpyruvate. Plu3042 acted next to
      transaminate the Plu3043 product, precluding spontaneous exocyclic double-bond
      isomerization and yielding 2,5-dihydrotyrosine. The enzymatic products most
      plausibly on path to H(2)Phe illustrate the versatile metabolic rerouting of
      prephenate from aromatic amino acid synthesis to antibiotic synthesis.

PMID- 21944751
TI  - Switching heterotrimeric G protein subunits with a chemical dimerizer.
AB  - The selective manipulation of single intracellular-signaling events remains one
      of the key tasks when studying signaling networks. Here, we demonstrate for the
      first time the stimulation of FKBP fusions of various subunits of heterotrimeric
      G proteins by the simple addition of the chemical dimerizer rapamycin. Activation
      of constitutively active Galpha(q), but not its GDP-bound form, leads to
      sustained oscillations of intracellular calcium and myo-inositol 1,4,5
      trisphosphate (InsP(3)) levels in HEK cells, independent of the activation of
      endogenous Galpha(q), in full agreement with the InsP(3)-Ca(2+) cross-coupling
      model of calcium oscillations. Rapamycin-induced translocation of wild-type
      Galpha(s) to the plasma membrane results in elevated cAMP levels. Activation of
      rapamycin-inducible Galpha(s) or Gbeta(1)gamma(2) evokes extensive modulation of
      ATP-induced calcium transients. The results demonstrate that inducible
      heterotrimeric G protein subunits will provide ways for dissecting G protein
      coupled receptor signaling.

PMID- 21944750
TI  - Expanded polyglutamine-binding peptoid as a novel therapeutic agent for treatment
      of Huntington's disease.
AB  - Polyglutamine(polyQ)-expanded proteins are potential therapeutic targets for the
      treatment of polyQ expansion disorders such as Huntington's disease (HD) and
      spinocerebellar ataxia type 3 (SCA3). Here, we used an amino-terminal fragment of
      a mutant Huntingtin protein (Htt-N-82Q) as bait in an unbiased screen of a 60,000
      peptoid library. Peptoid HQP09 was selected from the isolated hits and confirmed
      as a specific ligand of Htt-N-82Q and Atxn3-77Q mutant proteins in biochemical
      experiments. We identified three critical residues in the HQP09 sequence that are
      important for its activity and generated a minimal derivative, HQP09_9, which
      maintains the specific polyQ-binding activity. We demonstrated that HQP09 and
      HQP09_9 inhibited aggregation of Htt-N-53Q in vitro and exerted Ca(2+)
      stabilizing and neuroprotective effects in experiments with primary striatal
      neuronal cultures derived from HD mice. We further demonstrated that
      intracerebroventricular delivery of HQP09 to an HD mouse model resulted in
      reduced accumulation of mutant Huntingtin aggregates and improved motor
      behavioral outcomes. These results suggest that HQP09 and similar peptoids hold
      promise as novel therapeutics for developing treatments for HD, SCA3, and other
      polyglutamine expansion disorders.

PMID- 21944752
TI  - Coenzyme Q biosynthesis: Coq6 is required for the C5-hydroxylation reaction and
      substrate analogs rescue Coq6 deficiency.
AB  - Coenzyme Q (Q), an essential component of eukaryotic cells, is synthesized by
      several enzymes from the precursor 4-hydroxybenzoic acid. Mutations in six of the
      Q biosynthesis genes cause diseases that can sometimes be ameliorated by oral Q
      supplementation. We establish here that Coq6, a predicted flavin-dependent
      monooxygenase, is involved exclusively in the C5-hydroxylation reaction. In an
      unusual way, the ferredoxin Yah1 and the ferredoxin reductase Arh1 may be the in
      vivo source of electrons for Coq6. We also show that hydroxylated analogs of 4
      hydroxybenzoic acid, such as vanillic acid or 3,4-dihydroxybenzoic acid, restore
      Q biosynthesis and respiration in a Saccharomyces cerevisiae coq6 mutant. Our
      results demonstrate that appropriate analogs of 4-hydroxybenzoic acid can bypass
      a deficient Q biosynthetic enzyme and might be considered for the treatment of
      some primary Q deficiencies.

PMID- 21944753
TI  - A systematic family-wide investigation reveals that ~30% of mammalian PDZ domains
      engage in PDZ-PDZ interactions.
AB  - PDZ domains are independently folded modules that typically mediate protein
      protein interactions by binding to the C termini of their target proteins.
      However, in a few instances, PDZ domains have been reported to dimerize with
      other PDZ domains. To investigate this noncanonical-binding mode further, we used
      protein microarrays comprising virtually every mouse PDZ domain to systematically
      query all possible PDZ-PDZ pairs. We then used fluorescence polarization to
      retest and quantify interactions and coaffinity purification to test
      biophysically validated interactions in the context of their full-length
      proteins. Overall, we discovered 37 PDZ-PDZ interactions involving 46 PDZ domains
      (~30% of all PDZ domains tested), revealing that dimerization is a more
      frequently used binding mode than was previously appreciated. This suggests that
      many PDZ domains evolved to form multiprotein complexes by simultaneously
      interacting with more than one ligand.

PMID- 21944756
TI  - Design of a heterobivalent ligand to inhibit IgE clustering on mast cells.
AB  - We describe the design, synthesis, and characterization of a heterobivalent
      ligand (HBL) system that competitively inhibits allergen binding to mast cell
      bound IgE antibody, thereby inhibiting mast cell degranulation. HBLs are composed
      of a hapten conjugated to a nucleotide analog allowing simultaneous targeting of
      the antigen-binding site as well the "unconventional nucleotide binding site" on
      IgE Fab domains. Simultaneous bivalent binding to both sites provides HBLs with
      over 100-fold enhancement both in avidity for IgE(DNP) (K(d) = 0.33 MUM) and in
      inhibition of allergen binding to IgE(DNP) (IC(50) = 0.45 MUM) than the
      monovalent hapten (K(d)(mono) = 41 MUM; IC(50)(mono) = 55.4 MUM, respectively).
      In cellular assays, HBL2 effectively inhibits mast cell degranulation (IC(50) =
      15 MUM), whereas no inhibition is detected by the monovalent hapten. In
      conclusion, this study establishes the use of multivalency in a novel HBL design
      to inhibit mast cell degranulation.

PMID- 21944754
TI  - Inhibitors of tyrosine phosphatases and apoptosis reprogram lineage-marked
      differentiated muscle to myogenic progenitor cells.
AB  - Muscle regeneration declines with aging and myopathies, and reprogramming of
      differentiated muscle cells to their progenitors can serve as a robust source of
      therapeutic cells. Here, we used the Cre-Lox method to specifically label
      postmitotic primary multinucleated myotubes and then utilized small molecule
      inhibitors of tyrosine phosphatases and apoptosis to dedifferentiate these
      myotubes into proliferating myogenic cells, without gene overexpression. The
      reprogrammed, fusion competent, muscle precursor cells contributed to muscle
      regeneration in vitro and in vivo and were unequivocally distinguished from
      reactivated reserve cells because of the lineage marking method. The small
      molecule inhibitors downregulated cell cycle inhibitors and chromatin remodeling
      factors known to promote and maintain the cell fate of myotubes, facilitating
      cell fate reversal. Our findings enhance understanding of cell-fate determination
      and create novel therapeutic approaches for improved muscle repair.

PMID- 21944755
TI  - Activators of cylindrical proteases as antimicrobials: identification and
      development of small molecule activators of ClpP protease.
AB  - ClpP is a cylindrical serine protease whose ability to degrade proteins is
      regulated by the unfoldase ATP-dependent chaperones. ClpP on its own can only
      degrade small peptides. Here, we used ClpP as a target in a high-throughput
      screen for compounds, which activate the protease and allow it to degrade larger
      proteins, hence, abolishing the specificity arising from the ATP-dependent
      chaperones. Our screen resulted in five distinct compounds, which we designate as
      Activators of Self-Compartmentalizing Proteases 1 to 5 (ACP1 to 5). The compounds
      are found to stabilize the ClpP double-ring structure. The ACP1 chemical
      structure was considered to have drug-like characteristics and was further
      optimized to give analogs with bactericidal activity. Hence, the ACPs represent
      classes of compounds that can activate ClpP and that can be developed as
      potential novel antibiotics.

PMID- 21944757
TI  - Targeted disruption of the CCR5 gene in human hematopoietic stem cells stimulated
      by peptide nucleic acids.
AB  - Peptide nucleic acids (PNAs) bind duplex DNA in a sequence-specific manner,
      creating triplex structures that can provoke DNA repair and produce genome
      modification. CCR5 encodes a chemokine receptor required for HIV-1 entry into
      human cells, and individuals carrying mutations in this gene are resistant to HIV
      1 infection. Transfection of human cells with PNAs targeted to the CCR5 gene,
      plus donor DNAs designed to introduce stop codons mimicking the naturally
      occurring CCR5-delta32 mutation, produced 2.46% targeted gene modification. CCR5
      modification was confirmed at the DNA, RNA, and protein levels and was shown to
      confer resistance to infection with HIV-1. Targeting of CCR5 was achieved in
      human CD34(+) hematopoietic stem cells (HSCs) with subsequent engraftment into
      mice and persistence of the gene modification more than four months
      posttransplantation. This work suggests a therapeutic strategy for CCR5 knockout
      in HSCs from HIV-1-infected individuals, rendering cells resistant to HIV-1 and
      preserving immune system function.

PMID- 21944758
TI  - Fungal diversity in cow, goat and ewe milk.
AB  - Knowledge of fungal diversity in the environment is poor compared with bacterial
      biodiversity. In this study, we applied the denaturing high-performance liquid
      chromatography (D-HPLC) technique, combined with the amplification of the ITS1
      region from fungal rDNA, for the rapid identification of major fungal species in
      9 raw milk samples from cow, ewe and goat, collected at different periods of the
      year. A total of 27 fungal species were identified. Yeast species belonged to
      Candida, Cryptococcus, Debaryomyces, Geotrichum, Kluyveromyces, Malassezia,
      Pichia, Rhodotorula and Trichosporon genera; and mold species belonged to
      Aspergillus, Chrysosporium, Cladosporium, Engyodontium, Fusarium, Penicillium and
      Torrubiella genera. Cow milk samples harbored the highest fungal diversity with a
      maximum of 15 species in a single sample, whereas a maximum of 4 and 6 different
      species were recovered in goat and ewe milk respectively. Commonly encountered
      genera in cow and goat milk were Geotrichum candidum, Kluyveromyces marxianus and
      Candida spp. (C. catenulata and C. inconspicua); whereas Candida parapsilosis was
      frequently found in ewe milk samples. Most of detected species were previously
      described in literature data. A few species were uncultured fungi and others
      (Torrubiella and Malassezia) were described for the first time in milk.

PMID- 21944773
TI  - Late breast metastasis from resected lung cancer diagnosed by epidermal growth
      factor receptor gene mutation.
AB  - Primary lung cancer metastasizes to various organs, but rarely metastasizes to
      the breast. We report a case of breast metastasis from primary lung cancer, which
      was confirmed by the detection of the same epidermal growth factor receptor
      (EGFR) gene mutation.

PMID- 21944774
TI  - CT findings of intraductal papillary neoplasm of the bile duct: assessment with
      multiphase contrast-enhanced examination using multi-detector CT.
AB  - AIM: To evaluate multi-detector computed tomography (MDCT) findings of
      intraductal papillary neoplasm of the bile duct (IPNB), a neoplasm that is
      considered to be the biliary counterpart of pancreatic intraductal papillary
      mucinous neoplasm. MATERIALS AND METHODS: Two radiologists retrospectively
      evaluated multiphase contrast-enhanced CT images with 0.5 or 1mm collimation in
      37 consecutive patients with resected IPNB diagnosed by a single pathologist. The
      CT findings were correlated with the pathological findings concerning invasion of
      the surrounding organs and vessels. RESULTS: All patients showed bile duct
      dilatation. An intraductal mass was detected in 36 patients and the following
      findings were observed: extensive infiltration along the bile duct more than 20mm
      (n=32), compared with normal hepatic parenchyma, isodense or hyperdense during
      the late arterial phase (n=31), not hyperdense during the portal-venous and
      delayed phases (n=36), and intense enhancement rim at the base of the mass during
      the portal-venous or delayed phase (n=27). Parenchymal invasion of the
      surrounding organs was seen in eight of 16 tumours showing irregular or bulging
      margins. Vascular invasion was false positive in four of eight tumours.
      CONCLUSIONS: IPNB exhibits relatively characteristic findings with multiphase
      contrast-enhanced examination using MDCT. A tendency to overestimate invasion of
      the surrounding organs and vessels was seen.

PMID- 21944775
TI  - Imaging and management of vascular malformations.
AB  - Vascular malformations are a diffuse collection of abnormalities that are usually
      present at birth but may present any time during childhood or as an adult.
      Historically terminology has been complicated and used interchangeably causing
      confusion to patients and clinicians alike; however, a structured internationally
      agreed classification system exists. It is not uncommon for patients with
      vascular malformations to be referred to various specialties without obtaining a
      correct diagnosis and appropriate treatment. Vascular malformations can occur
      anywhere within the body and all patients will require imaging at some stage;
      therefore, it is important for all radiologists to be aware of the correct
      terminology and imaging characteristics. This review discusses classification and
      illustrates salient imaging findings and the modern approach to treatment of
      vascular malformations.

PMID- 21944776
TI  - Dental age assessment of southern Chinese using the United Kingdom Caucasian
      reference dataset.
AB  - Dental age assessment is one the most accurate methods for estimating the age of
      an unknown person. Demirjian's dataset on a French-Canadian population has been
      widely tested for its applicability on various ethnic groups including southern
      Chinese. Following inaccurate results from these studies, investigators are now
      confronted with using alternate datasets for comparison. Testing the
      applicability of other reliable datasets which result in accurate findings might
      limit the need to develop population specific standards. Recently, a Reference
      Data Set (RDS) similar to the Demirjian was prepared in the United Kingdom (UK)
      and has been subsequently validated. The advantages of the UK Caucasian RDS
      includes versatility from including both the maxillary and mandibular dentitions,
      involvement of a wide age group of subjects for evaluation and the possibility of
      precise age estimation with the mathematical technique of meta-analysis. The aim
      of this study was to evaluate the applicability of the United Kingdom Caucasian
      RDS on southern Chinese subjects. Dental panoramic tomographs (DPT) of 266
      subjects (133 males and 133 females) aged 2-21 years that were previously taken
      for clinical diagnostic purposes were selected and scored by a single calibrated
      examiner based on Demirjian's classification of tooth developmental stages (A-H).
      The ages corresponding to each stage of tooth developmental stage were obtained
      from the UK dataset. Intra-examiner reproducibility was tested and the Cohen
      kappa (0.88) showed that the level of agreement was 'almost perfect'. The
      estimated dental age was then compared with the chronological age using a paired
      t-test, with statistical significance set at p<0.01. The results showed that the
      UK dataset, underestimated the age of southern Chinese subjects by 0.24 years but
      the results were not statistically significant. In conclusion, the UK Caucasian
      RDS may not be suitable for estimating the age of southern Chinese subjects and
      there is a need for an ethnic specific reference dataset for southern Chinese.

PMID- 21944777
TI  - Trichostatin a promotes cardiomyocyte differentiation of rat mesenchymal stem
      cells after 5-azacytidine induction or during coculture with neonatal
      cardiomyocytes via a mechanism independent of histone deacetylase inhibition.
AB  - This study was to investigate the effect of trichostatin A (TSA), a histone
      deacetylase (HDAC) inhibitor, on cardiac differentiation of bone marrow
      mesenchymal stem cells (MSCs) in vitro. Rat MSCs were isolated and divided into
      six groups: 1) control; 2) 5-azacytidine treatment (5-aza,  10 MUM); 3) treatment
      with TSA (100, 300, and 500 nM); 4) treatment with 5-aza followed by incubation
      with TSA; 5) coculture with neonatal cardiomyocytes (CMs); and 6) treatment with
      TSA then coculture with CMs. HDAC activity was significantly inhibited in TSA
      treated cells with the maximal  inhibition after 24 h of exposure to TSA at 300
      nM. No changes in HDAC activity were observed in control, 5-aza-treated, or
      coculture groups. Following 7 days of differentiation, the expression of early
      cardiac transcription factors GATA-4, NKx2.5, MEF2c, and cardiac troponin T
      (cTnT) was  increased by 6-8 times in the cells in 5-aza-treated, coculture, or
      TSA-treated groups over control as determined using real-time PCR,
      immunofluorescence staining, and Western blotting. However, the percent cTnT
      positive cells were dramatically different with 0.7% for control, 10% for  5-aza
      treated, 25% for coculture, and 4% for TSA-treated group (500 nM). TSA treatment
      of the cells pretreated with 5-aza or cocultured with CMs dramatically increased
      the expression of GATA-4, NKx2.5, and MEF2c by 35-50 times over control. The cTnT
      protein expression was also significantly  increased by over threefold by TSA
      treatment (500 nM) in both 5-aza-treated and coculture group over control. The
      percent cTnT-positive cells in both 5-aza-pre-treated and coculture groups were
      significantly increased by TSA treatment after 1 week of differentiation by up to
      92.6% (from 10.3%  to 19.8%) and 23.9% (from 24.5% to 30.2%), respectively. These
      data suggested that TSA enhanced the cardiac differentiation of MSCs after 5-aza
      induction or during coculture with CMs through a mechanism beyond the inhibition
      of HDAC activity.

PMID- 21944778
TI  - Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes
      chromosome 9p-linked FTD and ALS.
AB  - Several families have been reported with autosomal-dominant frontotemporal
      dementia (FTD) and amyotrophic lateral sclerosis (ALS), genetically linked to
      chromosome 9p21. Here, we report an expansion of a noncoding GGGGCC
      hexanucleotide repeat in the gene C9ORF72 that is strongly associated with
      disease in a large FTD/ALS kindred, previously reported to be conclusively linked
      to chromosome 9p. This same repeat expansion was identified in the majority of
      our families with a combined FTD/ALS phenotype and TDP-43-based pathology.
      Analysis of extended clinical series found the C9ORF72 repeat expansion to be the
      most common genetic abnormality in both familial FTD (11.7%) and familial ALS
      (23.5%). The repeat expansion leads to the loss of one alternatively spliced
      C9ORF72 transcript and to formation of nuclear RNA foci, suggesting multiple
      disease mechanisms. Our findings indicate that repeat expansion in C9ORF72 is a
      major cause of both FTD and ALS.

PMID- 21944780
TI  - In vivo porcine left atrial wall stress: Effect of ventricular tachypacing on
      spatial and temporal stress distribution.
AB  - Animal models of ventricular tachypacing (VTP) have been successfully used to
      reproduce the relevant features observed in patients with atrial fibrillation,
      such as increased atrial pressure and volume, ion-channel alterations and
      fibrosis. After performing VTP on a healthy Yorkshire pig, we measured an
      increase in volume of 60%, a two-fold rise in pressure, and a complex pattern of
      local mechanical, histological and biochemical changes, including a generalized
      stiffening of the wall. A protocol recently developed was employed to generate
      computational models of the porcine left atrium mechanics in healthy conditions
      and after VTP. Comparison of the stress distribution in the healthy vs. VTP case
      provided a map of how pressure overload affects and modifies left atrium
      mechanics. Overall, a positive increase in stress was computed after the VTP
      treatment. Regions of large increase in the stresses post-VTP were the appendage
      boundaries, the area around the lower pulmonary vein and the area in the front of
      the atrium towards the appendage. Due to the elevated stress, the back of the
      atrium mainly modified its mechanical response, while the appendage remodeled
      both its shape and its mechanical properties. Large changes in the shape of the
      mitral valve annulus could be observed as a consequence of the remodeling in the
      front of the atrium. The relation between local mechanical stress and remodeling
      that emerges from the results is in agreement with our hypothesis that the
      structural changes in the atrium are a consequence of a stress-mediated
      mechanism.

PMID- 21944781
TI  - Assessment of anatomical frame variation effect on joint angles: A linear
      perturbation approach.
AB  - Although the interpretability and reliability of joint kinematics depends
      strongly on the accuracy and precision of determining the anatomical frame (AF)
      orientation, the exact dependency of joint angle error on AF misalignment is
      still not clear. To fully understand the behavior, this study uses linear
      perturbations to quantify joint angle error due to known modifications of the
      AFs, where the joint angles are calculated according to the Cardanic convention.
      The result is a functional representation of joint angle error with dependence on
      nominal joint angles and on the orientations of the alternative AFs relative to
      the nominal AFs. The results are validated using numerical analysis on knee joint
      angle data during walking. The derived relationship elucidates results from
      previous work studying this effect and allows AF differences to be inferred by
      joint angle curves when multiple sets of joint angle curves are collected
      simultaneously.

PMID- 21944782
TI  - Isolated right testicular pain for six days: an unusual presentation of occult
      abdominal aortic aneurysm leak.
AB  - Abdominal aortic aneurysm (AAA) rupture commonly presents with abdominal or lower
      back pain and haemodynamic instability. There have been case reports of co
      existing left testicular pain;(1) however, very few cases describe right
      testicular pain as the sentinel symptom. We discuss the case of a 75-year-old man
      who presented to the on-call urologists with a 6-day history of right testicular
      pain. On examination, a painless AAA was detected. The patient was stable and a
      CT scan demonstrated a large AAA extending into the right iliac vessels, with
      suggestion of leakage. Attempted emergency repair was unsuccessful and the
      patient died in theatre. This atypical presentation of occult aneurysm leak
      highlights the need for clinical vigilance in the older patient with seemingly
      benign groin symptoms, including isolated right testicular pain.

PMID- 21944779
TI  - A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21
      linked ALS-FTD.
AB  - The chromosome 9p21 amyotrophic lateral sclerosis-frontotemporal dementia (ALS
      FTD) locus contains one of the last major unidentified autosomal-dominant genes
      underlying these common neurodegenerative diseases. We have previously shown that
      a founder haplotype, covering the MOBKL2b, IFNK, and C9ORF72 genes, is present in
      the majority of cases linked to this region. Here we show that there is a large
      hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72 on the
      affected haplotype. This repeat expansion segregates perfectly with disease in
      the Finnish population, underlying 46.0% of familial ALS and 21.1% of sporadic
      ALS in that population. Taken together with the D90A SOD1 mutation, 87% of
      familial ALS in Finland is now explained by a simple monogenic cause. The repeat
      expansion is also present in one-third of familial ALS cases of outbred European
      descent, making it the most common genetic cause of these fatal neurodegenerative
      diseases identified to date.

PMID- 21944783
TI  - Transmural peritoneal adenomatoid tumour in the ileocaecal region causing massive
      haemoperitoneum and low gastrointestinal bleeding: differential diagnosis with
      capillary haemangiomas.
AB  - Peritoneal adenomatoid tumours are rare benign neoplasms originating from
      mesothelial cells. We present a case of peritoneal adenomatoid tumour penetrating
      into the bowel wall and causing massive intra- and extraluminal bleeding.

PMID- 21944784
TI  - Primary extraskeletal osteosarcoma of the seminal vesicle: a case report and
      literature review.
AB  - A primary extraskeletal osteosarcoma (EOS) is a rare tumour. An EOS of the
      seminal vesicle has not been reported in the literature. We describe a case of a
      seminal vesicle EOS initially detected as a pre-rectal mass on a routine
      transrectal ultrasound in a 48-year-old man. A computed tomography (CT) scan
      confirmed the tumour to be arising from the left seminal vesicle. A robot
      assisted laparoscopic seminal vesiculectomy was performed to avoid neurovascular
      bundle injury. Microscopic examination of the resected specimen showed a poorly
      differentiated osteosarcoma originating from the seminal vesicle. The patient
      received adjuvant chemotherapy. He is doing well without voiding or erectile
      dysfunction and he is tumour-free five months after surgery.

PMID- 21944785
TI  - Diffuse large B-cell lymphoma presenting as a chronic leg ulcer: the importance
      of repeat tissue biopsy.
AB  - Ulceration of the leg is often associated with significant consequences for both
      the individual and society. The diagnosis of chronic leg ulcer is not
      appropriate. Primary cutaneous diffuse large B-cell lymphoma (PCLBCL), leg type,
      is a distinct clinicopathological entity. Chemotherapy  in the form of R-CHOP
      (rituximab, cyclophosphamide, hydroxydaunorubicin, Oncovin and prednisolone) is
      considered to be the first line of treatment for these lymphomas. We report a 69
      year-old man who presented with chronic leg ulcer with a first negative biopsy
      and a diagnosis of PCLBCL, leg  type, verified on the subsequent biopsy. This
      case report emphasises the importance of differential diagnosis of lymphoma in
      non-healing ulcers and also the value of repeat tissue biopsy in cases with a
      negative initial result but strong clinical suspicion.

PMID- 21944786
TI  - Management of median arcuate ligament syndrome in patients who require
      pancreaticoduodenectomy.
AB  - Pancreaticoduodenectomy is the standard treatment for localised neoplasms of the
      pancreatic head. The operation can be performed safely in specialist units but
      good outcome is compromised if postoperative blood flow to the liver and biliary
      tree is inadequate. Coeliac artery occlusion  with blood supply to the liver
      arising from the superior mesenteric artery via the gastroduodenal artery is
      difficult to recognise, especially intraoperatively. Recognition of absent
      hepatic artery pulsation after occlusion of the gastroduodenal artery opens a
      dilemma: should the resection  be abandoned or should vascular reconstruction be
      undertaken, adding risk to an already complex procedure? We describe two cases
      with a resectable pancreatic endocrine tumour in which coeliac artery occlusion
      caused by median arcuate ligament compression was identified from cross-sectional
      imaging and reconstructions. We highlight two different strategies to correct
      the vascular insufficiency and allow safe pancreatic resection.

PMID- 21944787
TI  - Spontaneous psoas abscess: presenting with phlegmasia cerulea dolens.
AB  - Phlegmasia cerulea dolens (PCD) is a limb-threatening venous disorder involving
      massive proximal venous thrombosis. The clinical manifestations are of oedema,
      cyanosis and pain of lower extremity. Patients presenting with PCD have an
      underlying pathological condition that predisposes  to the thrombotic process. We
      report a diabetic patient who presented with PCD and septicaemia due to a
      spontaneous psoas abscess. Anticoagulation with heparin and treatment of the
      underlying psoas abscess led to complete resolution of symptoms. An understanding
      of the underlying pathological  process responsible is vital to early recognition
      and successful outcome in this rare limb- and life-threatening venous disorder.

PMID- 21944788
TI  - A case of widespread aortic thrombosis secondary to acute severe pancreatitis.
AB  - We offer this case for publication as we believe that this is the first report of
      widespread aortic thrombosis secondary to acute severe pancreatitis.

PMID- 21944789
TI  - Coil migration--a rare complication of endovascular exclusion of visceral artery
      pseudoaneurysms and aneurysms.
AB  - INTRODUCTION: We describe a case of metallic, angiographic coil migration,
      following radiological exclusion of a gastroduodenal artery pseudoaneurysm
      secondary to chronic pancreatitis. PATIENTS AND METHODS: A 55-year-old man
      presented to the out-patient clinic with chronic, intermittent, post-prandial,
      abdominal pain, associated with nausea, vomiting and weight loss. He was known to
      have chronic pancreatitis and liver disease secondary to alcohol abuse and
      previously underwent angiographic exclusion of a gastroduodenal artery
      pseudoaneurysm. During subsequent radiological and endoscopic investigation, an
      endovascular coil was discovered in the gastric pylorus, associated with
      ulceration and cavitation. This patient was managed conservatively and enterally
      fed via naso-jejunal catheter endoscopically placed past the site of the migrated
      coil. This patient is currently awaiting biliary bypass surgery for chronic
      pancreatitis, and definitive coil removal will occur concurrently. CONCLUSIONS:
      Literature review reveals that this report is only the eighth to describe coil
      migration following embolisation of a visceral artery pseudoaneurysm or aneurysm.
      Endovascular embolisation of pseudoaneurysms and aneurysms is generally safe and
      effective. More common complications of visceral artery embolisation include
      rebleeding, pseudoaneurysm reformation and pancreatitis.

PMID- 21944790
TI  - Peri-operative care series.
AB  - Failure to provide sufficient information to a patient when seeking consent can
      result in a claim in negligence. When determining what information to provide,
      you should be guided by what this particular patient needs to know in order to
      make an informed decision. Adult patients must be assumed to have capacity to
      give or withhold consent unless they are clearly unable to comprehend, retain or
      weigh in the balance the necessary information. Adults without capacity come
      under the protection of the mental Capacity act (adults with incapacity
      (Scotland) act in Scotland). as a result, they may when competent have nominated
      someone to make healthcare-related decisions on their behalf. If nobody has been
      appointed in this way by a patient it may be necessary to consult an independent
      mental capacity advocate. An adult with capacity has the right to refuse
      treatment on rational grounds, irrational grounds or, indeed, no grounds at all.

PMID- 21944791
TI  - Retroperitoneal tumours: review of management.
AB  - INTRODUCTION: The retroperitoneum can host a wide spectrum of pathologies,
      including a variety of rare benign tumours and malignant neoplasms that can be
      either primary or metastatic lesions. Retroperitoneal tumours can cause a
      diagnostic dilemma and present several therapeutic challenges  because of their
      rarity, relative late presentation and anatomical location, often in close
      relationship with several vital structures in the retroperitoneal space.
      MATERIALS AND METHODS: A comprehensive literature search was conducted using
      PubMed. Relevant international articles published  in the last ten years were
      assessed. The keywords for search purposes included: retroperitoneum, benign,
      sarcoma, neoplasm, diagnosis and surgery, radiotherapy, chemotherapy. The search
      was limited to articles published in English. All articles were read in full by
      the authors and selected  for inclusion based on relevance to this article.
      RESULTS: Tumours usually present late and cause symptoms or become palpable once
      they have reached a significant size. Retroperitoneal tumours are best evaluated
      with good quality cross-sectional imaging and preoperative histology by core 
      needle biopsy is required when imaging is non-diagnostic. Sarcomas comprise a
      third of retroperitoneal tumours. Other retroperitoneal neoplasms include
      lymphomas and epithelial tumours or might represent metastatic disease from known
      or unknown primary sites. The most common benign pathologies  encountered in the
      retroperitoneum include benign neurogenic tumours, paragangliomas, fibromatosis,
      renal angiomyolipomas and benign retroperitoneal lipomas. CONCLUSIONS: Complete
      surgical resection is the only potential curative treatment modality for
      retroperitoneal sarcomas and is best  performed in high-volume centres by a
      multidisciplinary sarcoma team. The ability completely to resect a
      retroperitoneal sarcoma and tumour grade remain the most important predictors of
      local recurrence and disease-specific survival.

PMID- 21944792
TI  - Measurement issues when assessing quality of life outcomes for different types of
      hernia mesh repair.
AB  - INTRODUCTION: The NHS is required to collect data from patient reported outcome
      measures (PROMs) for inguinal hernia surgery. We explored the use of one such
      measure, the Carolinas Comfort Scale((r)) (CCS), to compare long-term outcomes
      for patients who received two different types of mesh. The CCS questionnaire asks
      about mesh sensation, pain and movement limitations, and combines the answers
      into a total score. PATIENTS AND METHODS: A total of 684 patients were treated
      between January 2007 and August 2008 and were followed up in November 2009.
      RESULTS: Data on 215 patients who met the inclusion criteria were available (96
      patients who received SurgiproTM mesh and 119 who received ParieteneTM ProgripTM
      mesh). Recurrence rates were similar in the SurgiproTM group (2/96, 2.1%) and
      ProgripTM group (3/118, 2.5%) (Fisher's exact test = 1.0). Chronic pain occurred
      less frequently in the SurgiproTM group (11/95, 11.6%) than in the ProgripTM
      group (22/118, 18.6%) (p<0.157). Overall, 90% of CCS total scores indicated a
      good outcome (scores of 10 or less out of 115). A principal component analysis of
      the CCS found that responses clustered into two subscales: 'mesh sensation' and
      'pain+movement limitations'. The ProgripTM group had a slightly higher mesh
      sensation score (p<0.051) and similar pain+movement limitations scores (p<0.120).
      CONCLUSIONS: In this study of quality of life outcomes related to different mesh
      types, the CCS subscales were more sensitive to differences in outcome than the
      total CCS score for the whole questionnaire. Future research should consider
      using the CCS subscales rather than the CCS total score.

PMID- 21944793
TI  - Is primary endocrine therapy effective in treating the elderly, unfit patient
      with breast cancer?
AB  - INTRODUCTION: Elderly patients with oestrogen receptor (ER)-positive breast
      cancer wishing to avoid surgery or those who are considered unsuitable for a
      general anaesthetic may be treated with primary endocrine therapy. We have
      reviewed all patients with ER-positive breast cancer who were initially treated
      with primary hormone therapy (PHT) at a district general hospital in south Wales
      and investigated their outcome in order to evaluate the appropriateness of this
      method of managing breast cancer. MATERIALS AND METHODS: All patients with breast
      cancer who were initially treated with PHT between January 2002 and December 2008
      were identified from a single consultant's prospectively maintained database. For
      each patient the Charlson co-morbidity index was calculated to give an estimate
      of ten-year survival. Patients who had died during the study period were
      identified from hospital and cancer registries. RESULTS: A total of 83 cancers in
      82 patients with a median age of 81 years (range: 62-93 years) were included. All
      cancers were ER-positive. Six patients (7%) had a greater than 50% chance of
      surviving ten years, calculated using the Charlson index. The median follow-up
      period was 24 months (range: 6-72 months). Twelve patients (15%) had disease
      progression while taking PHT. Twenty-three patients (28%) have died (median time
      from diagnosis to death of 10.5 months, range: 1-77 months). Two patients (2%)
      experienced disease progression within six months of starting PHT and the number
      of patients whose cancer progressed increased with increasing length of follow
      up. Fourteen patients (17%) eventually underwent a wide local excision under
      local anaesthetic. CONCLUSIONS: PHT can be considered an effective treatment in
      this elderly, unfit population with the aim of stopping disease progression so
      that these patients die with their breast cancer, not of it.

PMID- 21944794
TI  - Simplified minimally invasive parathyroidectomy: a series of 100 cases and review
      of the literature.
AB  - INTRODUCTION: Conventional practice of parathyroidectomy has been collar incision
      with bilateral neck exploration and a four-gland evaluation. Our local practice
      involves simplified parathyroidectomy via mini-incision without routine use of
      intraoperative adjuncts. The aim of this study is to demonstrate that a good
      success rate can be achieved, which will hopefully encourage more to undertake
      minimally invasive parathyroid surgery. MATERIALS AND METHODS: A prospective case
      series of the first 100 patients undergoing minimally invasive parathyroidectomy
      (MIP) by a single surgeon at a single institution were included. Preoperatively,
      patients underwent ultrasonography (US) and/or a sestamibi (MIBI) scan for
      localisation. Parathyroidectomy was performed following an algorithm of
      intraoperative decisions. Serum calcium and/or parathyroid hormone levels were
      checked at follow-up. Postoperative normocalcaemia was considered success
      independent of serum parathyroid hormone levels RESULTS: The patients had a
      median age of 63 years. Of the 100 patients, 83 were female and 17 male. Seven
      patients had a conversion to bilateral exploration. The mean operative time for
      unilateral and bilateral exploration was 42.38 minutes and 76.43 minutes
      respectively. Separately, a MIBI scan and US lateralised the side of the lesion
      in 82.8% and 79.5% of cases respectively. When US and the MIBI scan agreed, the
      predictive accuracy of the side of the lesion was 87.5%. The majority of patients
      (96%) had a successful return to normocalcaemia. No complications were
      encountered. CONCLUSIONS: Excellent results are achievable with simplified MIP
      even without intraoperative adjuncts. Preoperative localisation is helpful in
      determining the side of incision. Our technique demonstrates a key principle of
      surgery: to keep things simple.

PMID- 21944795
TI  - Primary hyperparathyroidism: how many cases are being missed?
AB  - INTRODUCTION: Primary hyperparathyroidism (PHPT) is a common condition (250 per
      million population per year) with significant associated morbidity and mortality.
      Surgery is the only curative option for PHPT; results from medical treatment
      remain disappointing. The aim of this study was to evaluate the referral patterns
      of patients with PHPT and identify the number of missed cases with a biochemical
      diagnosis of PHPT. MATERIALS AND METHODS: All chemistries for Worcestershire were
      performed and analysed at the Worcestershire Royal Hospital. Patients with
      chronic renal failure were identified and excluded. Routes of patient referral
      were identified and missed cases documented. General practitioners (GPs) were
      contacted by letter for all patients not referred or treated. Outcomes of
      diagnosis and specialist assessment were recorded. RESULTS: A total of 102 cases
      of PHPT were identified: 64 (62.7%) remained untreated and without a specialist
      referral in place, 36 (35.3%) had undergone parathyroidectomy and 2 (2.0%) were
      being monitored. The GP response rate was 90% (46/51). Of these, 30 (65%) were
      subsequently referred, 9 (20%) underwent repeat tests with a view to referral and
      7 (15%) were lost to follow up. CONCLUSIONS: A significant proportion of patients
      with PHPT remain in the community untreated and having not seen a specialist. All
      patients should be referred to a specialist for assessment and consideration of
      surgical treatment and follow-up. Improvements in GP education and referral
      systems are required if patients are to benefit.

PMID- 21944796
TI  - Satisfaction with conduit harvest site scars in coronary bypass surgery.
AB  - INTRODUCTION: Scars from conduit harvesting are common in coronary artery bypass
      patients. As an outward manifestation of surgery, the scar is important in
      patient perception of operative success and quality of care received. The aim of
      this study was to determine patient satisfaction with scars from radial artery
      and saphenous vein harvests at a tertiary cardiothoracic centre. METHODS: We
      surveyed 62 patients attending follow-up appointment using the Patient Scar
      Assessment Questionnaire. This is a reliable and valid measure of a patient's
      perception of scarring. Data were analysed using ratings of scar attributes and
      features. We compared findings according to site and patient choice of scar site
      using the Mann-Whitney U test. RESULTS: Analysis of both global and summative
      ratings showed no overall statistical differences between arm and leg scars
      (p<0.05). However, patients given a choice gave significantly higher ratings of
      scar appearance on global ratings versus those given no choice. Patients also
      reported greater satisfaction with appearance than those given no choice on
      summative ratings (p<0.05). CONCLUSIONS: Patient choice of conduit site is an
      important determinant of the overall rating of scar appearance. Overall
      satisfaction is influenced by scar appearance. Clinicians should ensure, wherever
      possible, that they involve patients in conduit site selection.

PMID- 21944797
TI  - Retroperitoneal lymph node dissection for metastatic germ cell tumours.
AB  - INTRODUCTION: In the North Trent Cancer network (NTCN) patients requiring
      retroperitoneal lymphadenectomy for metastatic testicular cancer have been
      treated by vascular service since 1990. This paper reviews our experience and
      considers the case for involvement of vascular surgeons in the management of
      these tumours. PATIENTS AND METHODS: Patients referred by the NTCN to the
      vascular service for retroperitoneal lymphadenectomy between 1990 and 2009 were
      identified through a germ cell database. Data were supplemented by a review of
      case notes to record histology, intraoperative and postoperative details.
      RESULTS: A total of 64 patients were referred to the vascular service for
      retroperitoneal lymph node dissection, with a median age of 29 years (16-63
      years) and a median follow-up of 4.9 years. Ten patients died: eight from tumour
      recurrence, one from septicaemia during chemotherapy and one by suicide. Of the
      54 who survived, 7 were alive with residual masses and 47 patients were disease
      free at the last follow-up. Sixteen patients required vascular procedures: four
      had aortic repair (fascia), three had aortic replacement (spiral graft), four had
      inferior vena cava resection, two had iliac artery replacement and two had iliac
      vein resection. CONCLUSIONS: Retroperitoneal lymph node dissection often involves
      mobilisation and/or the resection/replacement of major vessels. We recommend that
      a vascular surgeon should be a part of testicular germ cell multidisciplinary
      team.

PMID- 21944798
TI  - Variations in the anatomical distribution of peripheral vascular disease
      according to gender.
AB  - BACKGROUND: While large epidemiological studies have suggested that the male
      gender is more frequently afflicted with intermittent claudication, there is
      little data whether there are gender differences in the distribution of
      peripheral vascular disease (PVD). The aim of this study  was to clarify this
      issue on the basis of angiographic findings in patients presenting with
      claudication. PATIENTS AND METHODS: The radiology department computerised
      database was used to identify all lower limb angiograms performed for
      investigation of PVD. Patients undergoing incomplete  assessment and those with
      normal angiograms were excluded. Demographic details for each patient were
      collected together with details of uni- or bilaterality of disease, the number of
      lesions present and their anatomical distribution according to the major named
      vessels. Only lesions reported  as radiologically significant were included in
      the analysis. RESULTS: Five hundred consecutive angiograms fitting the defined
      study criteria were assessed. There were 310 males and 190 females giving a male
      to female ratio of 1.6:1. The most common distribution for both genders was
      multiple  bilateral lesions. There were no significant differences in the number
      of stenoses in terms of ratio of bilateral to unilateral (2.39 vs 2.77) or ratio
      of multiple to single lesions (1.5 vs 1.7) between the female and male groups.
      Disease was more common in males at all anatomical locations,  the most
      significant differences being for lesions of the common femoral and profunda
      femoris arteries. CONCLUSIONS: PVD is more commonly diagnosed in males than
      females. The disease process is more commonly bilateral in both genders and PVD
      affects more numerous sites in the male claudicant  than in the female
      claudicant. Nevertheless, there does not appear to be any difference in the
      anatomical distribution of disease between genders.

PMID- 21944799
TI  - Clopidogrel: is a surgical delay necessary in fractured neck of femur?
AB  - INTRODUCTION: This paper assesses the outcomes of patients after surgery for a
      proximal femur fracture while on clopidogrel. It describes a single-centre
      retrospective observational study over a two-year period. PATIENTS AND METHODS: A
      total of 31 surgical patients were included in this study. Of these, 28 were on
      clopidogrel and 3 on dipyridamole. Patients were split into subgroups based on
      when surgery took place and the type of hip fracture. The 'early surgery' (<48
      hours from admission to theatre) group contained 16 patients (51.6%) and the
      'late surgery' (>48 hours) group composed 15 patients (48.4%). Type of surgery
      performed and pre-and postoperative haemoglobin (Hb) levels were recorded.
      Furthermore, the number of units of blood transfused per patient as well as
      complications before and after surgery were noted. RESULTS: A significantly
      larger mean hb drop occurred in the early surgery group (3.2g/dl) compared with
      the late surgery group (2.3g/dl) (p=0.027). The mean length of inpatient stay was
      21 days in the early and 23 days in the late group (p=0.456). A significantly
      larger hb mean drop occurred in patients with extracapsular hip fractures
      (3.4g/dl; n=16) compared with patients with intracapsular fractures (2.3g/dl;
      n=15) (p=0.020). The extracapsular patients had longer stays in hospital: 24.5
      days versus 19.8 days in the intracapsular group (p=0.521). There was no
      statistical difference in the 30-day mortality between the early surgery (3/16
      deaths) and late surgery (2/15 deaths) groups (p=0.481). CONCLUSIONS: Patients
      with extracapsular fractures, treated with early surgery, appear to be most at
      risk of complications after surgery.

PMID- 21944800
TI  - Hip resurfacing revision rates: radiological audit of risk factors.
AB  - INTRODUCTION: We performed a retrospective radiological audit of the hip
      resurfacings carried out in our trust over a five-year period. Abnormal cup
      inclination angle (CIA) and stem shaft angle (SSA) are recognised risk factors
      for revision in hip resurfacing. Our aims were to identify the CIA and SSA for
      hip resurfacings in our trust, to determine the revision rate in a CIA of >=60
      degrees  and an SSA of >0 degrees  varus, thereby identifying a high risk group
      for close, long-term follow up. METHODS: A total of 247 patients underwent hip
      resurfacing in our trust between April 2003 and March 2008. The CIA and SSA were
      recorded. Of the 247 patients, 26 were excluded as there were no appropriate
      radiographs and so results were analysed for 221 patients. RESULTS: The mean CIA
      was 47.6 degrees . Over a third of the patients (34%) had a CIA of >50 degrees 
      and 13% had >60 degrees . The mean SSA was 1.4 degrees  varus. Over two-thirds of
      the patients (67%) had a varus SSA. There were six revisions but one was excluded
      as it was secondary to infection. The revision rate was 10% in patients with a
      CIA of >=60 degrees  and 1% in those with a CIA of <60 degrees  (p=0.017), and 1%
      in a varus and 4% in a valgus SSA ((p)>0.05) respectively. CONCLUSIONS: The
      measurement of the CIA and SSA in hip resurfacings has identified a high risk
      group for close long-term follow up. There is already a 10% revision rate in
      those patients with a CIA of >60 degrees . Hip resurfacing may generate a large
      revision burden in the 'average' surgeon's hands and all hospitals/surgeons
      should review their radiological outcomes critically and identify those at risk
      of revision.

PMID- 21944802
TI  - Suction drain using a drip-giving set: a simple and cheap technique.

PMID- 21944803
TI  - Reducing particulate metal wound contamination when removing volar locking plates
      in the distal radius.

PMID- 21944804
TI  - Replacing the suprapubic catheter that has 'fallen out'.

PMID- 21944805
TI  - Laparoscopic reinsertion/exchanges of peritoneal dialysis catheters using the
      modified Y-TEC((r)) system.

PMID- 21944806
TI  - An innovative technique for removal of a broken intramedullary hip screw.

PMID- 21944807
TI  - A simple and cost-effective technique to prevent turbulence and improve
      visualisation during shoulder arthroscopy.

PMID- 21944808
TI  - 'Bale hook' needle mount and suturing techniques.

PMID- 21944809
TI  - A simple technique to avoid blockage of the suction system in laparoscopic
      procedures.

PMID- 21944810
TI  - A new technique for hamstring donor site blockade in anterior cruciate ligament
      reconstruction.

PMID- 21944811
TI  - Lagging the Synthes((r)) locking compression proximal femoral plate 4.5/5.0 to
      the proximal femur.

PMID- 21944812
TI  - A temporary solution to light source failure in proctoscopy/rigid sigmoidoscopy.

PMID- 21944813
TI  - A simple technique to prevent screws dropping during open reduction internal
      fixation of distal radius fractures.

PMID- 21944814
TI  - Comment on: The role of the chest x-ray for the acute abdomen in the 21st
      century.

PMID- 21944815
TI  - Comment on: Hand-held device for smoke extraction.

PMID- 21944816
TI  - Relative risk.

PMID- 21944817
TI  - Comment on: General anaesthetics: why have two when one will do?

PMID- 21944818
TI  - Comment on: Bare below the elbows.

PMID- 21944819
TI  - Comment on: Surgical treatment of ingrown toenails in children.

PMID- 21944820
TI  - Comment on: Minimising perioperative homologous blood transfusions.

PMID- 21944821
TI  - Comment on: Venous thromboembolism prophylaxis following hip arthroplasty.

PMID- 21944822
TI  - A Delphi study on National PICU nursing research priorities in Australia and New
      Zealand.
AB  - BACKGROUND: There is a lack of evidence to direct and support nursing practice in
      the specialty of paediatric intensive care (PIC). The development of national PIC
      nursing research priorities may facilitate the process of undertaking clinical
      research and translating evidence into practice. PURPOSE: To (a) identify
      research priorities for the care of patients and their family as well as for the
      professional needs of PIC nurses, (b) foster nursing research collaboration, (c)
      develop a research agenda for PIC nurses. METHODS: Over 13 months in 2007-2008, a
      three-round questionnaire, using the Delphi technique, was sent to all specialist
      level registered nurses working in Australian and New Zealand PICUs. This method
      was used to identify and prioritise nursing research topics. Content analysis was
      used to analyse Round I data and descriptive statistics for Round II and III
      data. RESULTS: In Round I, 132 research topics were identified, with 77 research
      priorities (mdn>6, mean MAD(median) 0.68+/-0.01) identified in subsequent rounds.
      The top nine priorities (mean>6 and median>6) included patient issues related to
      neurological care (n=2), pain/sedation/comfort (n=3), best practice at the end of
      life (n=1), and ventilation strategies (n=1), as well as two priorities related
      to professional issues about nurses' stress/burnout and professional development
      needs. CONCLUSION: The research priorities identified reflect important issues
      related to critically ill patients and their family as well as to the nurses
      caring for them. These priorities can be used for the development of a research
      agenda for PIC nursing in Australia and New Zealand.

PMID- 21944823
TI  - Pigmentation of skin graft is improved by cryopreservation of human skin with
      trehalose.
AB  - PURPOSE: It is well-known that hyperpigmentation of a skin graft occurs more
      frequently in patients of color. The objective of this study was to investigate a
      modified protocol in which trehalose is combined with dimethyl sulfoxide (Me2SO)
      to improve the pigmentation of skin grafts. MATERIALS AND METHODS: Human skin
      samples were harvested from patients with breast cancer. Trehalose 0.5 mol/L
      combined with 10% v/v Me2SO was used as a cryoprotectant. Skin samples were
      divided into 3 groups: fresh (n = 10), cryopreserved with trehalose/Me2SO (n =
      10), and cryopreserved Me2SO alone (n = 10). The viability of skin was evaluated
      using hematoxylin and eosin staining, Ki-67 immunostaining, and by
      transplantation to immunodeficient mice. After transplantation, grafts were
      photographed and harvested for analysis by histologic and ultrastructural
      observations and cytokeratin 5/6 immunostaining. RESULTS: After cryopreservation,
      trehalose/Me2SO-cryopreserved skin maintained well-preserved epidermal and dermal
      structures when evaluated using hematoxylin and eosin staining. In the fresh and
      trehalose/Me2SO groups, no differences in Ki-67 positive unit values (26.79 +/-
      1.55 vs 26.04 +/- 1.15) were observed. When transplanted to immunodeficient mice,
      hyperpigmentation, melanocytes, and melanosomes were found in fresh skin. Skin
      cryopreserved with trehalose/Me2SO appeared to match harmoniously, cytokeratin
      5/6 immunostaining showed that some trehalose/Me2SO-cryopreserved skin grafts
      were of human origin and the rest of mouse origin. CONCLUSION: These results
      suggest that a combination of trehalose and Me2SO significantly increases the
      protective effect of skin tissues during cryopreservation. More importantly, this
      technique seems to prevent pigmentation of skin grafts.

PMID- 21944824
TI  - Semiautomatic segmentation for prostate brachytherapy: dosimetric evaluation.
AB  - PURPOSE: To demonstrate that manual prostate segmentation in transrectal
      ultrasound images can be replaced with semiautomatic segmentation. METHODS AND
      MATERIALS: Semiautomatic segmentation using a tapered ellipsoid model was applied
      to transrectal ultrasound images. Region-based volumetric evaluation was
      performed between original and physician-reviewed semiautomatic contours. For
      dosimetric assessment, treatment plans generated on semiautomatic contours were
      overlaid on physician-reviewed semiautomatic contours and dose parameters were
      computed. To establish a threshold for the acceptable amount of dosimetric
      degradation below which the adoption of semiautomatic planning is unacceptable,
      the range of variability in dosimetric quality attributed to manual variability
      was obtained and compared with that of semiautomatic contours. RESULTS: An
      average volume error (1-Dice similarity coefficient) of less than 7% between
      semiautomatic and manual volumes (140 cases) was obtained. The difference between
      the mean V(100) of plans created for semiautomatic contours then overlaid on
      physician-reviewed semiautomatic contours and the original V(100) values, that
      is, before overlaying on the physician-reviewed contours (41 cases) was lower
      than 5%. An average total duration of 2-4min, which includes algorithm
      initialization, 11.67+/-3.57s algorithm time, and contour modification is
      required per case. This algorithm is being used at the British Columbia Cancer
      Agency and to this date has been applied for the treatment of more than 600
      patients. CONCLUSIONS: In terms of volumetric and dosimetric accuracy, the
      proposed algorithm is a suitable replacement for manual segmentation in the
      context of our planning technique. The benefits are shorter segmentation times;
      greater consistency; less reliance on user experience; and smooth, symmetric
      contours.

PMID- 21944826
TI  - The effect of particle size on the cytotoxicity, inflammation, developmental
      toxicity and genotoxicity of silver nanoparticles.
AB  - Silver nanoparticles are of interest to be used as antimicrobial agents in wound
      dressings and coatings in medical devices, but potential adverse effects have
      been reported in the literature. The most pronounced effect of silver
      nanoparticles and the role of particle size in determining these effects, also in
      comparison to silver ions, are largely unknown. Effects of silver nanoparticles
      of different sizes (20, 80, 113 nm) were compared in in vitro assays for
      cytotoxicity, inflammation, genotoxicity and developmental toxicity. Silver
      nanoparticles induced effects in all endpoints studied, but effects on cellular
      metabolic activity and membrane damage were most pronounced. In all toxicity
      endpoints studied, silver nanoparticles of 20 nm were more toxic than the larger
      nanoparticles. In L929 fibroblasts, but not in RAW 264.7 macrophages, 20 nm
      silver nanoparticles were more cytotoxic than silver ions. Collectively, these
      results indicate that effects of silver nanoparticles on different toxic
      endpoints may be the consequence of their ability to inflict cell damage. In
      addition, the potency of silver in the form of nanoparticles to induce cell
      damage compared to silver ions is cell type and size-dependent.

PMID- 21944827
TI  - Multi-functional core-shell hybrid nanogels for pH-dependent magnetic
      manipulation, fluorescent pH-sensing, and drug delivery.
AB  - Remotely optical sensing and drug delivery using an environmentally-guided
      magnetically-driven hybrid nanogel particle could allow for medical diagnostics
      and treatment. Such multifunctional hybrid nanogels (<200 nm) were prepared
      through the first synthesis of magnetic Ni NPs, followed by a moderate growth of
      fluorescent metallic Ag on the surface of Ni NPs, and then a coverage of a pH
      responsive copolymer gel shell of poly(ethylene glycol-co-methacrylic acid) [p(EG
      MAA)] onto the Ni-Ag bimetallic NP cores (18 +/- 5 nm). The introduction of the
      pH-responsive p(EG-MAA) gel shell onto the magnetic and fluorescent Ni-Ag NPs
      makes the polymer-bound Ni-Ag NPs responsive to pH over the physiologically
      important range 5.0-7.4. The hybrid nanogels can adapt to surrounding pH and
      regulate the sensitivity in response to external magnetic field (such as a small
      magnet of 0.1 T), resulting in the accumulation of the hybrid nanogels within the
      duration from hours to a few seconds as the pH value decreases from 7.4 to 5.0.
      The pH-dependent magnetic response characteristic of the hybrid nanogels were
      further integrated with the pH change to fluorescent signal transduction and pH
      regulated anticancer drug (a model drug 5-fluorouracil) delivery functions. The
      hybrid nanogels can overcome cellular barriers to enter the intracellular region
      and light up the mouse melanoma B16F10 cells. The multiple responsive hybrid
      nanogel that can be manipulated in tandem endogenous and exogenous activation
      should enhance our ability to address the complexity of biological systems.

PMID- 21944825
TI  - The central role of calcium in the effects of cytokines on beta-cell function:
      implications for type 1 and type 2 diabetes.
AB  - The appropriate regulation of intracellular calcium is a requirement for proper
      cell function and survival. This review focuses on the effects of proinflammatory
      cytokines on calcium regulation in the insulin-producing pancreatic beta-cell and
      how normal stimulus-secretion coupling, organelle function, and overall beta-cell
      viability are impacted. Proinflammatory cytokines are increasingly thought to
      contribute to beta-cell dysfunction not only in type 1 diabetes (T1D), but also
      in the progression of type 2 diabetes (T2D). Cytokine-induced disruptions in
      calcium handling result in reduced insulin release in response to glucose
      stimulation. Cytokines can alter intracellular calcium levels by depleting
      calcium from the endoplasmic reticulum (ER) and by increasing calcium influx from
      the extracellular space. Depleting ER calcium leads to protein misfolding and
      activation of the ER stress response. Disrupting intracellular calcium may also
      affect organelles, including the mitochondria and the nucleus. As a chronic
      condition, cytokine-induced calcium disruptions may lead to beta-cell death in
      T1D and T2D, although possible protective effects are also discussed. Calcium is
      thus central to both normal and pathological cell processes. Because the tight
      regulation of intracellular calcium is crucial to homeostasis, measuring the
      dynamics of calcium may serve as a good indicator of overall beta-cell function.

PMID- 21944828
TI  - Effects of fibrin pad hemostat on the wound healing process in vivo and in vitro.
AB  - Fibrin Pad is a hemostatic pad designed to control surgical-related bleeding. It
      consists of a fully absorbable composite matrix scaffold coated with human
      derived active biologics that immediately form a fibrin clot upon contact with
      targeted bleeding surfaces. Studies were conducted to investigate the effect of
      Fibrin Pad and its biologics-free composite matrix component (Matrix) on the
      wound healing process in in vitro and in vivo models. Fibrin Pad was evaluated in
      solid organ, soft tissue defects, and subcutaneous tissues. Immunocompromised
      rodents were used to avoid xeno-mediated responses. Extracts created from both
      materials were evaluated for biological activity using in vitro cell culture
      assays. Neither Fibrin Pad nor Matrix alone showed any inhibition of the wound
      healing of treated defect sites. An apparent accelerated healing was noted in the
      soft tissue and subcutaneous tissue defects with Fibrin Pad as compared to
      Matrix. Both materials showed desirable properties associated with tissue
      scaffolds. The in vitro study results show that Fibrin Pad extract can induce
      dose-dependent increases in fibroblast proliferation and migration. These studies
      confirm that the biologic components of Fibrin Pad can enhance wound healing
      processes in in vitro assays and fully support wound healing at the site of in
      vivo application.

PMID- 21944829
TI  - Biomimetic nanofibrous scaffolds for bone tissue engineering.
AB  - Bone tissue engineering is a highly interdisciplinary field that seeks to tackle
      the most challenging bone-related clinical issues. The major components of bone
      tissue engineering are the scaffold, cells, and growth factors. This review will
      focus on the scaffold and recent advancements in developing scaffolds that can
      mimic the natural extracellular matrix of bone. Specifically, these novel
      scaffolds mirror the nanofibrous collagen network that comprises the majority of
      the non-mineral portion of bone matrix. Using two main fabrication techniques,
      electrospinning and thermally-induced phase separation, and incorporating bone
      like minerals, such as hydroxyapatite, composite nanofibrous scaffolds can
      improve cell adhesion, stem cell differentiation, and tissue formation. This
      review will cover the two main processing techniques and how they are being
      applied to fabricate scaffolds for bone tissue engineering. It will then cover
      how these scaffolds can enhance the osteogenic capabilities of a variety of cell
      types and survey the ability of the constructs to support the growth of
      clinically relevant bone tissue.

PMID- 21944830
TI  - The implications of cross-regional differences for the design of In-vehicle
      Information Systems: a comparison of Australian and Chinese drivers.
AB  - The increasing global distribution of automobiles necessitates that the design of
      In-vehicle Information Systems (IVIS) is appropriate for the regions to which
      they are being exported. Differences between regions such as culture, environment
      and traffic context can influence the needs, usability and acceptance of IVIS.
      This paper describes two studies aimed at identifying regional differences in
      IVIS design needs and preferences across drivers from Australia and China to
      determine the impact of any differences on IVIS design. Using a questionnaire and
      interaction clinics, the influence of cultural values and driving patterns on
      drivers' preferences for, and comprehension of, surface- and interaction-level
      aspects of IVIS interfaces was explored. Similarities and differences were found
      between the two regional groups in terms of preferences for IVIS input control
      types and labels and in the comprehension of IVIS functions. Specifically,
      Chinese drivers preferred symbols and Chinese characters over English words and
      were less successful (compared to Australians) at comprehending English
      abbreviations, particularly for complex IVIS functions. Implications in terms of
      the current trend to introduce Western-styled interfaces into other regions with
      little or no adaptation are discussed.

PMID- 21944831
TI  - Effect of organic acids and mannanoligosaccharide on excretion of Salmonella
      typhimurium in experimentally infected growing pigs.
AB  - The effect of organic acids and mannanoligosaccharide addition to the diet was
      assessed in pigs orally inoculated with Salmonella typhimurium. Forty-six growers
      were distributed among four treatments: Basal Diet (BD); BD+encapsulated organic
      acids; BD+free organic acids; BD+mannanoligosaccharide. Seroconversion was
      monitored, and feces and tissue samples were tested for Salmonella isolation. No
      treatment prevented the carrier state, but a tendency of lower fecal excretion
      was observed in the group treated with mannanoligosaccharide.

PMID- 21944832
TI  - A diet lower in digestible carbohydrate results in lower postprandial glucose
      concentrations compared with a traditional canine diabetes diet and an adult
      maintenance diet in healthy dogs.
AB  - The aim of this study was to compare the effects of three diets with varying
      macronutrient and fibre contents on postprandial plasma glucose, triglyceride,
      free fatty acid, and insulin concentrations over a 12 h period in 12 healthy
      neutered lean dogs. Each diet was fed to each dog for 3 weeks in a three-period
      cross-over study. Plasma analyte concentrations were measured prior to and after
      a meal at the end of the third week of each period. Postprandial glucose
      concentrations for the moderate carbohydrate and fibre diet were 0.4-0.7 mmol/L
      (8-12 mg/dL) lower than for both higher carbohydrate diets (p<=0.02).
      Postprandial glucose, insulin, and triglyceride concentrations in some dogs did
      not return to baseline by 12 h after feeding of each of the three diets. These
      results indicate that the moderate carbohydrate and fibre diet warrants
      evaluation in diabetic dogs. Variables should be measured over at least 12 h
      after feeding to fully evaluate postprandial dietary effects on these analytes.

PMID- 21944833
TI  - Secretory virulence factors produced by Staphylococcus aureus isolates obtained
      from mastitic bovine milk--effect on bovine polymorphonuclear neutrophils.
AB  - The aim of the research was to test whether exogenic virulence factors secreted
      by Staphylococcus aureus isolates are involved in mechanisms that allow the
      bacteria to modulate and evade phagocytosis by bovine polymorphonuclear
      neutrophils. The research was based on the comparison of the effects of
      supernatants, prepared from cultures of 30 S. aureus isolates, on the functional
      properties of bovine neutrophils in vitro. S. aureus isolates were collected from
      milk samples from cows with clinical mastitis. Supernatants, which were used to
      treat leukocytes, were prepared from 18 h S. aureus cultures. Exogenic virulence
      factors secreted by S. aureus isolates significantly influenced the phagocytosis
      parameters evaluated. Depending on their leukotoxic or superantigenic properties,
      supernatants could affect the ingestion process, and also showed an influence on
      the digestion efficiency and phagocytosis carried out by bovine polymorphonuclear
      neutrophils in vitro.

PMID- 21944834
TI  - The normal distribution of thoracoabdominal aorta small branch artery ostia.
AB  - The purpose of this study was to determine the normal distribution of aortic
      branch artery ostia. CT scans of 100 subjects were retrospectively reviewed. The
      angular distributions of the aorta with respect to the center of the T3 to L4
      vertebral bodies, and of branch artery origins with respect to the center of the
      aorta were measured. At each vertebral body level the distribution of
      intercostal/lumbar arteries and other branch arteries were calculated. The
      proximal descending aorta is posteriorly placed becoming a midline structure, at
      the thoracolumbar junction, and remains anterior to the vertebral bodies within
      the abdomen. The intercostal and lumbar artery ostia have a distinct
      distribution. At each vertebral level from T3 caudally, one intercostal artery
      originates from the posterior wall of the aorta throughout the thoracic aorta,
      while the other intercostal artery originates from the medial wall of the
      descending thoracic aorta high in the chest, posteromedially from the mid
      thoracic aorta, and from the posterior wall of the aorta low in the chest.
      Mediastinal branches of the thoracic aorta originate from the medial and anterior
      wall. Lumbar branches originate only from the posterior wall of the abdominal
      aorta. Aortic branch artery origins arise with a bimodal distribution and have a
      characteristic location. Mediastinal branches of the thoracic aorta originate
      from the medial and anterior wall. Knowing the location of aortic branch artery
      ostia may help distinguish branch artery pseudoaneurysms from penetrating ulcers.

PMID- 21944835
TI  - Overweight is a risk factor for both erosive and non-erosive reflux disease.
AB  - INTRODUCTION: Studies have reported that the association between overweight and
      erosive oesophagitis is very strong, whilst seeming less consistent with non
      erosive reflux disease. AIM: We have hypothesized that this difference may be due
      to the heterogeneity of endoscopy-negative population. METHODS: We studied 81
      patients with erosive oesophagitis, 48 controls and 295 endoscopy-negative
      patients classified by impedance-pH-testing as: (1) pH-POS (abnormal acid
      exposure); (2) hypersensitive oesophagus (normal acid exposure/SAP+); (3)
      functional heartburn (normal acid exposure/SAP-). Body mass index was also
      calculated. RESULTS: Mean body mass index was significantly higher (p<0.05) in
      erosive oesophagitis than in endoscopy-negative patients as a whole and controls
      [27 (18-40) vs. 25 (16-48) vs. 23 (16-34)]. However, the separation of endoscopy
      negative patients showed that mean body mass index was higher (p<0.05) in those
      with increased acid exposure time [26 (18-45)] than in hypersensitive oesophagus
      [24 (16-48)]. The former subgroup was similar to erosive oesophagitis, whilst the
      latter one to both functional heartburn [23 (16-34)] and controls (p=ns).
      Increased body mass index represented a risk factor for erosive oesophagitis
      (odds ratio 1.4; 95% confidence interval, 1.2-1.6) and non-erosive reflux disease
      pH-POS subgroup (odds ratio 1.35; 95% confidence interval, 1.2-1.5). CONCLUSION:
      Our study shows that overweight represents an important risk factor for erosive
      oesophagitis and pH-POS non-erosive reflux disease and not for hypersensitive
      oesophagus and functional heartburn. This provides an explanation for the
      previously reported lesser role of this variable in non-erosive reflux disease
      population.

PMID- 21944836
TI  - When humans become animals: Development of the animal category in early
      childhood.
AB  - The current study examines 3- and 5-year-olds' representation of the concept we
      label 'animal' and its two nested concepts -animal(contrastive) (including only
      non-human animals) and animal(inclusive) (including both humans and non-human
      animals). Building upon evidence that naming promotes object categorization, we
      introduced a novel noun for two distinct objects, and analyzed children's
      patterns of extension. In Experiment 1, children heard a novel noun in
      conjunction with two non-human animals (dog, bird). Here, both 3- and 5-year-olds
      readily accessed animal(contrastive) and extended the noun systematically to
      other (previously un-named) non-human animals. In Experiment 2, children heard a
      novel noun in conjunction with a human and non-human animal. Here, 5-year-olds
      (but not 3-year-olds) accessed animal(inclusive) and extended the noun
      systematically to humans and non-human animals. These results underscore the
      developmental challenge facing young children as they identify the scope of the
      fundamental biological term 'animal' and its corresponding, nested concept(s).

PMID- 21944837
TI  - Prevention of medical accidents caused by defective surgical instruments.
AB  - BACKGROUND: The malfunctioning of surgical instruments may lead to serious
      medical accidents. Limited information is available on the risk of defective
      instruments. The purpose of these study is to demonstrate the features of
      defective surgical instruments, to establish a strategy to reduce the risk of
      medical accidents. METHODS: We studied 19,474 consecutive operations during 2007
      to 2009 at our hospital. The data on defective instruments were collected based
      on the orders for repair of broken instruments and reports of near-miss
      incidents. Adverse events caused by defective instruments were also identified
      from reports of near-miss incidents. RESULTS: A total of 1,775 nonfunctioning
      instruments were identified during the study period. Of these, 112 were found
      during operation. More than half of the defective instruments were tissue
      grasping instruments, bone-boring/gnawing instruments, and instruments for
      endoscopic surgery. Wearing out and inappropriate use of instruments were 2 major
      causes of defects. The rest of the causes consisted of inadequate inspection and
      factory defects. Two near-miss incidents (incidence 10 per 100,000 operations) in
      endoscopic surgery were potentially critical, but the postoperative course was
      uneventful in each patient. The incidence of defects adjusted by the number of
      operations demonstrated that bone-boring/gnawing instruments and instruments for
      endoscopic surgery tend to be broken during surgery. Without inspection by the
      manufacturer, the incidence would be much higher for endoscopic instruments.
      CONCLUSION: Our data suggest that the appropriate use and adequate inspection of
      particular types of instruments are key for reducing the risk of medical
      accidents caused by defective surgical instruments.

PMID- 21944838
TI  - Enhanced photocatalytic activity of Bi2WO6 with oxygen vacancies by zirconium
      doping.
AB  - To overcome the drawback of low photocatalytic efficiency brought by electron
      hole recombination, Bi(2)WO(6) photocatalysts with oxygen vacancies were
      synthesized by zirconium doping. The oxygen vacancies as the positive charge
      centers can trap the electron easily, thus inhibiting the recombination of charge
      carriers and prolonging the lifetime of electron. Moreover, the formation of
      oxygen vacancies favors the adsorption of O(2) on the semiconductor surface, thus
      facilitating the reduction of O(2) by the trapped electrons to generate
      superoxide radicals, which play a key role in the oxidation of organics. Visible
      light-induced photodegradation of rhodamine B (RhB) and phenol were carried out
      to evaluate the photoactivity of the products. The results showed that oxygen
      deficient Bi(2)WO(6) exhibited much enhanced photoactivity than the Bi(2)WO(6)
      photocatalyst free of oxygen deficiency. This work provided a new concept for
      rational design and development of high-performance photocatalysts.

PMID- 21944839
TI  - Impairment of carbon metabolism induced by the herbicide glyphosate.
AB  - The herbicide glyphosate reduces plant growth and causes plant death by
      inhibiting the biosynthesis of aromatic amino acids. The objective of this work
      was to determine whether glyphosate-treated plants show a carbon metabolism
      pattern comparable to that of plants treated with herbicides that inhibit
      branched-chain amino acid biosynthesis. Glyphosate-treated plants showed impaired
      carbon metabolism with an accumulation of carbohydrates in the leaves and roots.
      The growth inhibition detected after glyphosate treatment suggested impaired
      metabolism that impedes the utilization of available carbohydrates or energy at
      the expected rate. These effects were common to both types of amino acid
      biosynthesis inhibitors. Under aerobic conditions, ethanolic fermentative
      metabolism was enhanced in the roots of glyphosate-treated plants. This
      fermentative response was not related to changes in the respiratory rate or to a
      limitation of the energy charge. This response, which was similar for both types
      of herbicides, might be considered a general response to stress conditions.

PMID- 21944840
TI  - Even low levels of ambient air pollutants are associated with increased emergency
      department visits for hypertension.
AB  - BACKGROUND: Numerous studies have reported associations between air pollution and
      cardiovascular diseases. While several studies illustrate that exposures to air
      pollutants can elevate blood pressure, few have evaluated the clinical relevance
      of this relationship. Hence, we aimed to explore the associations between daily
      concentrations of several air pollutants and emergency department visits for
      hypertension. METHODS: Odds ratios (ORs) for emergency department visits for
      hypertension in Edmonton, Canada, from April 1992 to March 2002 were associated
      with pollutant levels (CO, NO(2), SO(2), O(3), and particulate matter [PM] < 10
      microns [PM(10)] and < 2.5 microns [PM(2.5)] in aerodynamic diameter,
      respectively) by means of a case-crossover technique with time-stratified
      strategy to define controls. The analysis was performed for all (N = 5365), male
      (N = 2069), and female (N = 3296) patients and for six air pollutants lagged by 0
      to 9 days. ORs and their 95% confidence intervals (CIs) were reported for an
      increase in an interquartile range (IQR) for each pollutant. RESULTS: We observed
      associations for all patients and levels of NO(2) (IQR = 12.8 parts per billion;
      OR, 1.06; 95% CI, 1.00-1.12), SO(2) (IQR = 2.3 parts per billion; OR, 1.04; 95%
      CI, 1.00-1.08), and PM(10) (IQR = 15.0 MUg/m(3); OR, 1.06; 95% CI, 1.01-1.11) for
      lag day 3, as well as for PM(10) (IQR = 15.0 MUg/m(3); OR, 1.06; 95% CI, 1.01
      1.11) and PM(2.5) (IQR = 6.2 MUg/m(3); OR, 1.07; 95% CI, 1.01-1.11) for lag day
      6. CONCLUSIONS: These findings support the contention that ambient pollution can
      produce clinically meaningful increases in blood pressure.

PMID- 21944841
TI  - Is it time to reassess colon cancer screening recommendations and acknowledge
      ethnic disparities?

PMID- 21944842
TI  - Early detection, prevention and management of cutaneous adverse events due to
      sorafenib: recommendations from the Sorafenib Working Group.
AB  - Cutaneous adverse events commonly reported with tyrosine kinase inhibitors (TKIs)
      in the treatment of malignancies, represent an important clinical concern since
      they can limit the optimal use of these novel drugs. Although there are numerous
      reports in the literature of these events there are no practical guidelines on
      how they should be managed. The Sorafenib Working Group (SWG) was established
      with the objective of developing recommendations to allow the early detection,
      prevention and management of cutaneous adverse events in everyday clinical
      practice. The SWG was a multidisciplinary team made up of experts in the field
      who were closely involved in the sorafenib clinical development program. This
      review provides an overview of the nature and incidence of cutaneous adverse
      events which manifest with sorafenib treatment and provides recommendations for
      their early detection and effective management in clinical practice.

PMID- 21944843
TI  - Variability of respiratory symptoms in severe COPD.
AB  - INTRODUCTION: While it is known that asthma symptoms have a very variable
      pattern, the general belief is that the respiratory symptoms in COPD patients
      usually present little or no variability. Nevertheless, COPD patients report
      having "bad days". The objective of this present study was to evaluate the
      variability of the respiratory symptoms and their impact on the daily activities
      of a cohort of Spanish COPD patients. METHOD: We present the results of the
      Spanish patients who participated in a cross-sectional epidemiological study
      carried out in 17 European countries. Pulmonologists and Family Care physicians
      recruited patients with stable severe COPD (FEV1<50%). The perception of the
      patients on the variation in their symptoms was recorded by telephone interviews.
      RESULTS: A total of 472 patients provided data that was valid for analysis. Mean
      age was 68.6; 93% were men; mean FEV1(%) was 41%. 84.1% of the patients
      experimented at least one respiratory symptom in the previous week and 60.9%
      affirmed that their symptoms varied over the course of the day or week. The
      moment of the day when the symptoms were perceived to be more intense was during
      the morning. CONCLUSIONS: An important proportion of severe COPD patients
      perceive variability in their respiratory symptoms, with a greater intensity in
      the morning. The observation can have implications in treating patients with
      severe COPD as variability can be an initial sign of decompensation of the
      disease.

PMID- 21944844
TI  - Serological evidence of Toxoplasma gondii infection in captive marine mammals in
      Mexico.
AB  - Toxoplasma gondii infection in marine mammals is important because they are
      considered as a sentinel for contamination of seas with T. gondii oocysts, and
      toxoplasmosis causes mortality in these animals, particularly sea otters.
      Serological evidence of T. gondii infection was determined in 75 captive marine
      mammals from four facilities in southern and central geographical regions in
      Mexico using the modified agglutination test (MAT). Antibodies (MAT, 1:25 or
      higher) to T. gondii were found in 55 (87.3%) of 63 Atlantic bottlenose dolphins
      (Tursiops truncatus truncatus), 3 of 3 Pacific bottlenose dolphins (Tursiops
      truncatus gillii), 2 of 4 California sea lions (Zalophus californianus), but not
      in 3 West Indian manatees (Trichechus manatus), and 2 Patagonian sea lions
      (Otaria flavescens). Seropositive marine mammals were found in all 4 (100%)
      facilities sampled. All marine mammals were healthy and there has not been any
      case of clinical toxoplasmosis in the facilities sampled for at least the last 15
      years. The seroprevalence of T. gondii infection in marine mammals of the same
      species did not vary significantly with respect to sex and age. This is the first
      report on the detection of antibodies to T. gondii in marine mammals in Mexico.

PMID- 21944845
TI  - Gurltia paralysans (Wolffhugel, 1933): description of adults and additional case
      reports of neurological diseases in three domestic cats from southern Chile.
AB  - Adults of Gurltia paralysans were obtained from veins of the spinal cord
      subarachnoid space from three domestic cats presenting with chronic
      paraparesis/paraplegia from rural areas of southern Chile. Four adult nematodes
      were collected (2 males and 2 females) were recovered from cat 1, 14 adult
      nematodes (12 females and 2 males) from cat 2, and 12 nematodes (10 females and 2
      males) were collected from cat 3. Parasite induced lesions that compromised
      subarachnoid vein microvasculature at the thoracic, lumbar, sacral spinal cord
      segments extending to conus medularis. Female nematodes measured 25 mm long
      (range=25-30 mm) and 0.1mm wide. Male measured a mean of 16 mm length (range=13
      18 mm) with a body diameter of 0.1mm (range=0.08-0.15 mm). The present study
      described structural features of G. paralysans, a rare parasite first reported in
      the 1930s, and provides additional reports on associated clinical and
      pathological findings in naturally infected domestic cats.

PMID- 21944846
TI  - Computational approaches to design a molecular imprinted polymer for high
      selective extraction of 3,4-methylenedioxymethamphetamine from plasma.
AB  - In this work, a molecular imprinted polymer (MIP) as a novel selective sorbent
      for extraction of 3,4-methylenedioxymethamphetamine (MDMA) from plasma samples
      was prepared. For selecting a more suitable monomer and polymerization solvent a
      methodology based on density functional theory calculations was developed. This
      computational design is based on the comparison of stabilization energies of the
      prepolymerization adducts between the template and different functional monomers.
      The effect of polymerization solvent was studied using of polarizable continuum
      model (PCM). The computational results revealed that the best suitable monomer
      and polymerization solvent for preparation of MIP is methacrylic acid (MAA) and
      chloroform, respectively. Also, another MIP with methacrylic acid (MAA) as
      monomer in acetonitrile was prepared to evaluate the validity of polarizable
      continuum model for selection of polymerization solvent. The performance of each
      polymer was evaluated by using Langmuir-Freundlich (LF) isotherm. As it is
      expected, the best results were obtained for the MIP which was prepared in
      chloroform. This MIP was used as a selective sorbent in solid-phase extraction
      coupled with high performance liquid chromatography-ultraviolet detector (MISPE
      HPLC-UV) for rapid screening of MDMA in human plasma. For the proposed MISPE-HPLC
      UV method, the linearity between responses (peak areas) and concentrations was
      found over the range of 3.6-11500 ng mL(-1) with a linear regression coefficient
      of 0.998. The limit of detection (LOD) and quantification (LOQ) in plasma were
      1.0 and 3.3 ng mL(-1), respectively. The %RSD (n=5) data for five plasma samples
      containing 15, 25, 50, and 100 ng mL(-1) of MDMA were 1.02, 1.12, 2.05, 2.54,
      respectively.

PMID- 21944847
TI  - Practical method transfer from high performance liquid chromatography to ultra
      high performance liquid chromatography: the importance of frictional heating.
AB  - In theory, with identical stationary phase chemistry, the transfer of an HPLC
      method to UHPLC conditions is straightforward and necessitates the calculation of
      new conditions based on column and instrument geometries. Occasionally,
      undesirable changes in selectivity, retention or efficiency have been reported
      and have been attributed to a frictional heating phenomenon that is due to the
      elevated generated pressure drop. In the present study, the frictional heating in
      a UHPLC system was evaluated experimentally under gradient elution conditions
      (acetonitrile/buffer at pH 3 and 9) with generated pressure drops in the range of
      100-1000 bar on both 1.0mm and 2.1mm I.D. columns using a mixture of 10
      representative basic, acidic and neutral pharmaceutical compounds. Under
      adiabatic conditions (i.e., still-air oven), the longitudinal temperature
      gradient was estimated at +4  degrees C, +8  degrees C and +16  degrees C at 300,
      600 and 1000 bar, respectively, on a 2.1mm I.D. column using an empirical
      measurement procedure. With the 1.0mm I.D. column, these values were reduced to
      +3  degrees C, +6  degrees C and +12  degrees C, respectively. Finally, various
      approaches to eliminate or at least to reduce the effect of frictional heating
      are briefly discussed.

PMID- 21944848
TI  - A liquid chromatography-electrospray ionization-mass spectrometry method for
      quantification of cyclotides in plants avoiding sorption during sample
      preparation.
AB  - Cyclotides are plant-produced, bioactive, cyclic mini-proteins with interesting
      pharmaceutical and agricultural applications. A reverse phase liquid
      chromatography electrospray ionization mass spectrometry (RP-LC-ESI-MS) method
      for analysis of cyclotides in plant materials with a minimum of sample pre
      treatment is presented. Three exemplary cyclotides (kalata B1, kalata B2 and
      cycloviolacin O2) were used as reference substances for the method development.
      Linearity (r(2)>0.99) was achieved in the concentration range 0.05-10 mg/L and
      the limit of detection was 1.7-4.0 MUg/L. The present study is the first to
      demonstrate that cyclotides dissolved in water sorb to glass vials, but the
      addition of 15% of acetonitrile or 40 mg/L of bovine serum albumin is sufficient
      to keep the cyclotides in solution. Cyclotides were extracted from candied
      violets, violet tea, and the plants Oldenlandia affinis and Viola odorata using
      70% methanol containing 0.1% formic acid (v/v). The plant content was determined
      to be 23.5-14,200 MUg/g (dry weight). The highest content of cyclotide was found
      in wild Danish V. odorata, and it is the highest content of cyclotide in a plant
      reported hitherto. Candied violets contained 0.00-8.66 MUg/g (dry weight), while
      no cyclotides were detected in commercial violet tea.

PMID- 21944849
TI  - Peak clustering in two-dimensional gas chromatography with mass spectrometric
      detection based on theoretical calculation of two-dimensional peak shapes: the
      2DAid approach.
AB  - A method is presented to facilitate the non-target analysis of data obtained in
      temperature-programmed comprehensive two-dimensional (2D) gas chromatography
      coupled to time-of-flight mass spectrometry (GC*GC-ToF-MS). One main difficulty
      of GC*GC data analysis is that each peak is usually modulated several times and
      therefore appears as a series of peaks (or peaklets) in the one-dimensionally
      recorded data. The proposed method, 2DAid, uses basic chromatographic laws to
      calculate the theoretical shape of a 2D peak (a cluster of peaklets originating
      from the same analyte) in order to define the area in which the peaklets of each
      individual compound can be expected to show up. Based on analyte-identity
      information obtained by means of mass spectral library searching, the individual
      peaklets are then combined into a single 2D peak. The method is applied, amongst
      others, to a complex mixture containing 362 analytes. It is demonstrated that the
      2D peak shapes can be accurately predicted and that clustering and further
      processing can reduce the final peak list to a manageable size.

PMID- 21944850
TI  - A bone sample cleaning method using trypsin for the isolation of DNA.
AB  - Cleaning the surface of bone samples is a necessary step to remove contaminants
      prior to isolating DNA for forensic DNA analysis. In this study, a simple trypsin
      method for cleaning bone samples prior to DNA isolation was developed. Cleaning
      the surface of human bone samples was achieved by the application of trypsin
      solution. Light microscopy and scanning electron microscopy results indicated
      that trypsin treatment was effective in removing the outer surface of bone
      samples. The yield of DNA isolated from trypsin-treated bone samples was
      sufficient for subsequent short tandem repeat (STR) analysis. STR analysis
      revealed no adverse effect on the DNA profile after the trypsin treatment. The
      data suggest that this trypsin method can potentially be an alternative cleaning
      method to mechanical cleaning methods.

PMID- 21944851
TI  - Genetic variation of 15 autosomal microsatellite loci in a Nayarit population
      (Mexico).
AB  - Fifteen STRs are studied to determine the allele frequencies' distribution and to
      evaluate the homogeneity of Nayarit populations. This study allows the
      identification of forensic efficiency parameters to be used in forensic genetics
      and to explore the genetic similarities between Nayarit and the neighboring
      countries such as Mexico, Brazil, Puerto Rico, Guatemala, Honduras, Bolivia and
      Costa Rica. The Hardy-Weinberg equilibrium, expected heterozygosity, matching
      probability, and power of discrimination, were calculated in the Nayarit
      population. We found that with respect to the studied markers, Nayarit genetic
      structure is homogeneous. In this study, it is established that Nayarit is
      genetically similar to the South American Mestizo population. The distribution of
      a set of these 15 STRs was analyzed with other South American populations as well
      as in the extensive set of neighboring populations from the literature (USA,
      Europe and Africa). We found significant differences exist between the isolated
      populations (Huastecos, Otomi from Sierra Madre and from Ixmiquilpan Valley) and
      Mestizo populations. Statistical analysis supports that Americans actual
      inhabitants and Europeans are genetically similar, while Africans and isolated
      populations from South America have more genetic differences.

PMID- 21944852
TI  - Substituted indole-1-acetic acids as potent and selective CRTh2 antagonists
      discovery of AZD1981.
AB  - Novel indole-3-thio-, 3-sulfonyl- and 3-oxy-aryl-1-acetic acids are reported
      which are potent, selective antagonists of the chemoattractant receptor
      homologous expressed on Th2 lymphocytes receptor (CRTh2 or DP2). Optimization
      required maintenance of high CRTh2 potency whilst achieving a concomitant
      reduction in rates of metabolism, removal of cyp p450 inhibition and minimization
      of aldose reductase and aldehyde reductase activity. High quality compounds
      suitable for in vivo studies are highlighted, culminating in the discovery of
      AZD1981 (22).

PMID- 21944853
TI  - Mepyramine-JNJ7777120-hybrid compounds show high affinity to hH(1)R, but low
      affinity to hH(4)R.
AB  - In literature, a synergism between histamine H(1) and H(4) receptor is discussed.
      Furthermore, it was shown, that the combined application of mepyramine, a H(1)
      antagonist and JNJ7777120, a H(4) receptor ligand leads to a synergistic effect
      in the acute murine asthma model. Thus, the aim of this study was to develop new
      hybrid ligands, containing one H(1) and one H(4) pharmacophor, connected by an
      appropriate spacer, in order to address both, H(1)R and H(4)R. Within this study,
      we synthesized nine hybrid compounds, which were pharmacologically characterized
      at hH(1)R and hH(4)R. The new compounds revealed (high) affinity to hH(1)R, but
      showed only low affinity to hH(4)R. Additionally, we performed molecular dynamic
      studies for some selected compounds at hH(1)R, in order to obtain information
      about the binding mode of these compounds on molecular level.

PMID- 21944854
TI  - Design, synthesis, and structure-activity relationships of spirolactones bearing
      2-ureidobenzothiophene as acetyl-CoA carboxylases inhibitors.
AB  - The co-crystal structure of the human acetyl-coenzyme A 2 (ACC2) carboxyl
      transferase domain and the reported compound CP-640186 (1b) suggested that two
      carbonyl groups are essential for potent ACC2 inhibition. By focusing on
      enhancing the interactions between the two carbonyl groups and the amino acid
      residues Gly(2162) and Glu(2230), we used ligand- and structure-based drug design
      to discover spirolactones bearing a 2-ureidobenzothiophene moiety.

PMID- 21944855
TI  - Synthesis and evaluation of pyridazinone-phenethylamine derivatives as selective
      and orally bioavailable histamine H3 receptor antagonists with robust wake
      promoting activity.
AB  - A series of pyridazinone-phenethylamine derivatives with moderate to low
      nanomolar affinity for rat and human H(3)R are described. These analogs exhibited
      excellent selectivity and metabolic stability, with acceptable rat
      pharmacokinetic properties. In vivo, 7 and 11 demonstrated potent H(3)R
      functional antagonism in the rat dipsogenia model and robust wake-promoting
      activity in the rat electroencephalogram/electromyography (EEG/EMG) model.

PMID- 21944856
TI  - Tetrahydroquinolines as a novel series of nonsteroidal selective androgen
      receptor modulators: structural requirements for better physicochemical and
      biological properties.
AB  - A rationally designed tetrahydroquinoline (1) for nonsteroidal selective androgen
      receptor modulators was modified for the exploration of promising compounds by
      Grieco three-component condensation using various dienophiles. Based on the in
      vitro effects and physicochemical properties of the synthesized compounds,
      compound 4c was selected for further study. Compound 4c increased the femoral
      bone mineral density as much as DHT, but it reduced the uterus effect compared
      with DHT in ovariectomized rats. Thus, compound 4c has desirable osteoanabolic
      effects with weak undesirable effects on the uterus in a female osteoporosis
      model.

PMID- 21944858
TI  - Identification of novel plasmin inhibitors possessing nitrile moiety as warhead.
AB  - Lysine-nitrile derivatives having a trisubstituted benzene, which belongs to a
      new chemical class, were prepared and tested for inhibitory activities against
      plasmin and the highly homologous plasma kallikrein and urokinase. The use of the
      novel chemotype in the development of plasmin inhibitors has been demonstrated by
      derivatives of compound 9.

PMID- 21944857
TI  - Halogen substituents on the aromatic moiety of the tetracaine scaffold improve
      potency of cyclic nucleotide-gated channel block.
AB  - A series of new tetracaine derivatives with substituents on the aromatic ring was
      prepared and evaluated for block of retinal rod cyclic nucleotide-gated (CNG)
      channels. Aromatic substitutions had little effect starting with the basic
      tetracaine scaffold, but electron-withdrawing substituents significantly improved
      the blocking potency of an octyl-tail derivative of tetracaine. In particular,
      halogen substitutions at either the 2- or 3-position on the ring resulted in
      compounds that were up to eight-fold more potent than the parent octyl-tail
      derivative and up to 50-fold more potent than tetracaine.

PMID- 21944859
TI  - Synthesis and properties of novel 2'-O-alkoxymethyl-modified nucleic acids.
AB  - Novel 2'-O-modified oligoribonucleotides with alkoxymethyl skeletons were
      synthesized, and their ability to hybridize complementary nucleic acids and their
      nuclease resistance were analyzed. The hybridization ability was improved by
      introducing electron-withdrawing groups and the increases in melting temperature
      (T(m) value) was particularly high for chlorine-substituted compounds. Nuclease
      resistance of these 2'-O-alkoxymethylated oligomers was lower than expected, but
      cyano substitution resulted in a higher nuclease resistance than 2'-O
      methylation.

PMID- 21944860
TI  - Vitamin B6s inhibit oxidative stress caused by Alzheimer's disease-related Cu(II)
      beta-amyloid complexes-cooperative action of phospho-moiety.
AB  - Cu(II) complexes of Alzheimer's disease-related beta-amyloid (Abeta) peptides
      exhibit metal-centered oxidation chemistry. The metallo-Abeta complexes are the
      hallmark of the disease and have been attributed to the generation of reactive
      oxygen species (ROS), causing oxidative stress. In this communication, the
      inhibitions of the oxidative activity of Cu(II)-Abeta by vitamin B6 compounds
      pyridoxamine (PM), pyridoxine (PN), pyridoxal (PL), and pyridoxal-5'-phosphate
      (PLP) are presented. These B6's are competitive inhibitors toward dopamine
      oxidation by Cu(II)-Abeta(1-20), with K(i) values of 1.4, 8.3, 1.2, and 0.2mM,
      respectively. The phospho-moiety in PLP seems to exhibit cooperative inhibition,
      affording a clue for future design of inhibitors.

PMID- 21944861
TI  - Integrating food web diversity, structure and stability.
AB  - Given the unprecedented rate of species extinctions facing the planet,
      understanding the causes and consequences of species diversity in ecosystems is
      of paramount importance. Ecologists have investigated both the influence of
      environmental variables on species diversity and the influence of species
      diversity on ecosystem function and stability. These investigations have largely
      been carried out without taking into account the overarching stabilizing
      structures of food webs that arise from evolutionary and successional processes
      and that are maintained through species interactions. Here, we argue that the
      same large-scale structures that have been purported to convey stability to food
      webs can also help to understand both the distribution of species diversity in
      nature and the relationship between species diversity and food web stability.
      Specifically, the allocation of species diversity to slow energy channels within
      food webs results in the skewed distribution of interactions strengths that has
      been shown to confer stability to complex food webs. We end by discussing the
      processes that might generate and maintain the structured, stable and diverse
      food webs observed in nature.

PMID- 21944862
TI  - Remote processing of pancreas can restore normal glucose homeostasis in
      autologous islet transplantation after traumatic whipple pancreatectomy:
      technical considerations.
AB  - An emergency autologous islet transplant after a traumatic Whipple operation and
      subsequent total pancreatectomy was performed for a 21-year-old patient who was
      wounded with multiple abdominal gunshot wounds. After Whipple pancreatectomy, the
      remnant pancreas (63.5 g), along with other  damaged organs, was removed by the
      surgeons at Walter Reed Army Medical Center (WRAMC) and shipped to Diabetes
      Research Institute (DRI) for islet isolation. The pancreas was preserved in UW
      solution for 9.25 h prior to islet isolation. Upon arrival, the organ was
      visually inspected; the pancreatic  head was missing, the rest of the pancreas
      was damaged and full of blood; the tail looked normal. A 16-gauge catheter was
      inserted into the main duct and directed towards tail of the pancreas after the
      dissection of main duct in the midbody of the pancreas. The pancreas was
      distended with  collagenase solution (Roche MTF) through the catheter. During 10
      min of intraductal delivery of enzyme, the gland was distended uniformly. No
      leakage of the solution was observed. The pancreas was transferred to a Ricordi
      chamber for automated mechanical and enzymatic digestion. Islets were  purified
      using a COBE 2991 cell processor. Islet equivalents (IEQ; 221,250) of 40% purity
      and 90% viability were recovered during the isolation, which were shipped back to
      WRAMC and infused by intraportal injection into the patient. Immediate islet
      function was demonstrated by the rapid elevation  of serum C peptide followed by
      insulin independence with near normal oral glucose tolerance test (OGTT) 1 and 2
      months later. It is possible to restore near normal glucose tolerance with
      autologous islet transplantation after total pancreatectomy even with suboptimal
      number of islets while  confirming that islets processed at a remote site are
      suitable for transplantation.

PMID- 21944864
TI  - Crossover and maximal fat-oxidation points in sedentary healthy subjects:
      methodological issues.
AB  - AIM: Our study aimed to assess the influence of protocol on the crossover point
      and maximal fat-oxidation (LIPOX(max)) values in sedentary, but otherwise
      healthy, young men. METHODS: Maximal oxygen intake was assessed in 23 subjects,
      using a progressive maximal cycle ergometer test. Twelve sedentary males (aged
      20.5+/-1.0 years) whose directly measured maximal aerobic power (MAP) values were
      lower than their theoretical maximal values (tMAP) were selected from this group.
      These individuals performed, in random sequence, three submaximal graded exercise
      tests, separated by three-day intervals; work rates were based on the tMAP in one
      test and on MAP in the remaining two. The third test was used to assess the
      reliability of data. Heart rate, respiratory parameters, blood lactate, the
      crossover point and LIPOX(max) values were measured during each of these tests.
      RESULTS: The crossover point and LIPOX(max) values were significantly lower when
      the testing protocol was based on tMAP rather than on MAP (P<0.001). Respiratory
      exchange ratios were significantly lower with MAP than with tMAP at 30, 40, 50
      and 60% of maximal aerobic power (P<0.01). At the crossover point, lactate and 5
      min postexercise oxygen consumption (EPOC(5 min)) values were significantly
      higher using tMAP rather than MAP (P<0.001). During the first 5 min of recovery,
      EPOC(5 min) and blood lactate were significantly correlated (r=0.89; P<0.001).
      CONCLUSION: Our data show that, to assess the crossover point and LIPOX(max)
      values for research purposes, the protocol must be based on the measured MAP
      rather than on a theoretical value. Such a determination should improve
      individualization of training for initially sedentary subjects.

PMID- 21944863
TI  - Intrauterine infection and preterm labor.
AB  - Preterm labor is defined as labor that begins before 37 completed weeks of
      pregnancy. More than 12% of infants born in the USA are preterm. At least 40% of
      preterm births are associated with intrauterine infection. Toll-like receptors
      (TLRs) are members of a family of cell-surface proteins responsible for
      recognition of a diverse spectrum of bacterial, viral and fungal pathogens. TLRs
      initiate the host innate (i.e. non-adaptive) immune response, inducing a
      proinflammatory cascade involving cytokines, chemokines, prostaglandins, and
      other effector molecules that result in the characteristic phenomena of labor,
      such as uterine contractions and rupture of fetal membranes. These cascades may
      also be activated by mechanisms that are not primarily infectious but are
      accompanied by inflammatory responses. Now that the molecular mechanisms linking
      infection and labor have been, to a large extent, elucidated, the challenge is to
      identify points of overlap with non-infectious causes of labor and to find
      intervention strategies that can minimize the negative impact of preterm
      delivery.

PMID- 21944865
TI  - Chinese characters elicit face-like N170 inversion effects.
AB  - Recognition of both faces and Chinese characters is commonly believed to rely on
      configural information. While faces typically exhibit behavioral and N170
      inversion effects that differ from non-face stimuli (Rossion, Joyce, Cottrell, &
      Tarr, 2003), the current study examined whether a similar reliance on configural
      processing may result in similar inversion effects for faces and Chinese
      characters. Participants were engaged in an orientation judgment task (Experiment
      1) and a one-back identity matching task (Experiment 2). Across two experiments,
      the N170 was delayed and enhanced in magnitude for upside-down faces and compound
      Chinese characters, compared to upright stimuli. The inversion effects for these
      two stimulus categories were bilateral for latency and right-lateralized for
      amplitudes. For simple Chinese characters, only the latency inversion effects
      were significant. Moreover, the size of the right-hemisphere inversion effects in
      N170 amplitude was larger for faces than Chinese characters. These findings show
      the N170 inversion effects from non-face stimuli closely parallel effects seen
      with faces. Face-like N170 inversion effects elicited by Chinese compound
      characters were attributed to the difficulty of part-whole integration as well as
      the disrupted regularity in relational information due to inversion. Hemispheric
      difference in Chinese character processing is also discussed.

PMID- 21944866
TI  - Common polymorphisms in the GH/IGF-1 axis contribute to growth in extremely tall
      subjects.
AB  - CONTEXT/OBJECTIVE: The growth hormone (GH)/insulin-like growth factor-1(IGF-1)
      axis is the key regulator of somatic growth in humans and its genes are plausible
      candidates to study the genetics of height variation. Here, we studied
      polymorphic variation in the GH/IGF-1 axis in the extremely tall Dutch. METHODS:
      Case-control study of 166 tall cases with height >2 SDS and 206 controls with
      normally distributed height <2 SDS. Excluded were subjects with endocrine
      disorders or growth syndromes. We analyzed genomic DNA at 7 common polymorphisms
      in the GH-1, GH receptor (GHR), IGF-1 and IGFBP-3 genes. RESULTS: The association
      of the GH-1 1663 SNP with tall stature approached statistical significance, with
      the T-allele more present in the tall (allele frequency (AF): 0.44 vs. 0.36;
      p=0.084). Moreover, haplotype frequencies at this locus were significantly
      different between cases and controls, with the GGT haplotype most commonly seen
      in cases (p=0.01). Allele frequencies of GHR polymorphisms were not different.
      For the IGF-1 CA-repeat we observed a higher frequency of homozygous 192-bp
      carriers among tall males compared to control males (AF: 0.62 vs. 0.55; p=0.02).
      The IGFBP-3 -202 C-allele occurred more frequently in cases than in controls (AF:
      0.58 vs. 0.50; p=0.002). Within cases, those carrying one or two copies of the 
      202 C-allele were significantly taller than AA genotype carriers (AC, p=0.028 and
      CC, p=0.009). Serum IGFBP-3 levels were highest in AA genotype carriers, the -202
      SNP explained 5.8% of the variation. CONCLUSION: Polymorphic variation in the GH
      1, IGF-1 and IGFBP-3 genes is associated with extremely tall stature. In
      particular, the IGFBP-3 -202 SNP is associated not only with being very tall but
      also with height variation within the tall.

PMID- 21944867
TI  - Global hormone profiling of murine placenta reveals Secretin expression.
AB  - OBJECTIVE: To elucidate and categorize the murine placental hormones expressed
      across gestation, including the expression of hormones with previously
      undescribed roles. STUDY DESIGN: Expression levels of all genes with known or
      predicted hormone activity expressed in two separate tissues, the placenta and
      maternal decidua, were assessed across a timecourse spanning the full lifetime of
      the placenta. Novel expression patterns were confirmed by in situ hybridization
      and protein level measurements. RESULTS: A combination of temporal and spatial
      information defines five groups that can accurately predict the patterns of
      uncharacterized hormones. Our analysis identified Secretin, a novel placental
      hormone that is expressed specifically by the trophoblast at levels many times
      greater than in any other tissue. CONCLUSIONS: The characteristics of Secretin
      fit the paradigm of known placental hormones and suggest that it may play an
      important role during pregnancy.

PMID- 21944868
TI  - Linalool reduces the expression of 3-hydroxy-3-methylglutaryl CoA reductase via
      sterol regulatory element binding protein-2- and ubiquitin-dependent mechanisms.
AB  - We investigated hypocholesterolemic mechanisms of linalool, an aromatic anti
      oxidative monoterpene, which is abundant in teas and essential oils. Oral
      administration of linalool to mice for 6 weeks significantly lowered total and
      low-density lipoprotein cholesterol concentrations, and HMG-CoA reductase protein
      expression (-46%; P<0.05) by both transcriptional and posttranscriptional
      mechanisms. Linalool suppressed the gene expression of HMG-CoA reductase by
      reducing the binding of SREBP-2 to its promoter, as assessed by qPCR and
      chromatin immunoprecipitation, and by inducing ubiquitin-dependent proteolysis of
      the HMG-CoA reductase. These findings suggest that food molecules with a pleasant
      scent could exert beneficial metabolic effects through multiple mechanisms.

PMID- 21944869
TI  - Protein kinase C-theta in platelet activation.
AB  - Members of the protein kinase C (PKC) family of serine/threonine kinases have
      been implicated in several physiological processes regulating the activation
      response of platelets. They are involved in processes leading to granule
      secretion, integrin activation, platelet aggregation and spreading, and
      procoagulation. The protein kinase C theta (PKCtheta) isoform, which was
      originally identified in T lymphocytes, is also expressed at relatively high
      levels in platelets, wherein it is involved in the regulation of hemostasis and
      thrombosis. Recent studies suggest a role for PKCtheta in protease-activated
      receptor (PAR)-, glycoprotein VI (GPVI) receptor- and glycoprotein
      alpha(IIb)beta(3) integrin receptor-linked signal transduction pathways. The
      present review focuses on the latest observations relevant to the role of
      PKCtheta in platelet activation.

PMID- 21944870
TI  - [Medico-legal assessment in the sequelae of burns (2nd part): the lawyer's point
      of view].
AB  - Corporal prejudice rights have considerably progressed thanks to Dintilhac's
      nomenclature. The latter has created new headings of prejudice and has identified
      each of them. The aim is to harmonise experts' reports, claims for compensation,
      and court verdicts. This nomenclature has defined the notion of temporary
      aesthetic injury and indirect sexual harm, very useful in the expertise of burn
      sequelae, and thus permitting compensation of the professional prejudice.

PMID- 21944871
TI  - Cardiac tamponade as a life-threatening complication in hernia repair.
AB  - BACKGROUND: The placement of mesh in the repair of all types of hernia has been
      reported to decrease recurrence rates. There are several well known complications
      related to mesh repairs, including infection, erosion, seroma, and pain. Lesser
      reported are cardiac injuries secondary to anchoring of the mesh to the
      diaphragm. METHODS: We report 2 previously unreported, unpublished cases of
      cardiac tamponade after mesh fixation to the diaphragm and present a review of
      the literature and search of the US Food and Drug Administration's Manufacturer
      and User Device Experience (MAUDE) database. RESULTS: We reviewed a total of 10
      cases of cardiac tamponade in hiatal hernia repair, 6 resulting in patient
      mortality, 5 cases in ventral hernia repair, 4 being fatal. Ten cases were caused
      by the helical tacker, 2 by sutures, 1 by the straight stapler, and in 1 case the
      cause was not identified. CONCLUSION: When anchoring mesh to the diaphragm, it is
      necessary to consider the risk of injury to the heart and cardiac tamponade,
      especially if the helical tacker is used in this region. Only with appropriate
      awareness and recognition can this catastrophic complication be avoided.

PMID- 21944872
TI  - New treatment options for patients with metastatic castration-resistant prostate
      cancer.
AB  - Chemotherapy for men with metastatic castration-resistant prostate cancer (CRPC)
      conferred no survival advantage until 2004 when docetaxel was shown to improve
      survival when compared with mitoxantrone, which was approved for palliation of
      symptomatic disease in 1996. Since then, clinical trials have concentrated on
      three main populations of patients with metastatic CRPC: those who are
      chemotherapy naive and are asymptomatic or minimally symptomatic, those who need
      docetaxel therapy, and those who have received docetaxel previously and/or those
      with symptomatic disease. Over the last year, four Phase III therapeutic trials
      have met their primary endpoint of improved overall survival: sipuleucel-T in the
      pre-chemotherapy setting, cabazitaxel and abiraterone in the post-docetaxel
      setting, and radium-223 for those with symptomatic bone metastases who have
      received or are not suitable to receive docetaxel. In addition to these
      therapeutic trials, a Phase III head-to-head trial of denosumab compared to
      zoledronic acid showed that denosumab was superior to zoledronic acid in delaying
      or preventing skeletal related events. As a result, the treatment paradigm for
      metastatic CRPC is changing rapidly. This paper reviews the data from these five
      completed Phase III trials and places these new agents, as well as those in
      ongoing Phase III trials, in the context of the old treatment paradigm for
      metastatic CRPC and discusses some of the challenges ahead for determining
      optimal timing and sequencing of treatments for metastatic CRPC.

PMID- 21944873
TI  - Seasonal dynamics of biting midges (Diptera: Ceratopogonidae: Culicoides), the
      potential vectors of bluetongue virus, in Sweden.
AB  - The outbreak of bluetongue (BT) in northern Europe 2006 initiated the monitoring
      of vectors, biting midges of the genus Culicoides in Sweden. In order to
      determine the diversity, distribution and seasonal dynamics of Culicoides, weekly
      collections were made during 2008 and during March-December 2009 using the
      Ondestepoort Veterinary Institute black light trap. Twenty sampling sites were
      selected in 12 provinces. In total of 30,704 Culicoides were collected in 2008
      and 32,252 in 2009. The most abundant species were the potential vectors of BTV
      Culicoides obsoletus/C. scoticus that comprised of 77% of the total catches.
      Other biting midges collected were Culicoides impunctatus (9%), Culicoides
      grisescens (3%), Culicoides punctatus (2%), Culicoides chiopterus (2%) and
      Culicoides pulicaris (2%). Culicoides obsoletus/C. scoticus were most abundant
      during May-June and August-September. The majority of the species were active
      from March to November in 2008 and April to October in 2009. Species considered
      as potential vectors of bluetongue virus (BTV) occurred as far north as latitude
      65 degrees N (Kalix).

PMID- 21944874
TI  - Treatment of sludge containing nitro-aromatic compounds in reed-bed mesocosms -
      Water, BOD, carbon and nutrient removal.
AB  - Since the mid-1970s, Sweden has been depositing 1 million ton d.w sludge/year,
      produced at waste water treatment plants. Due to recent legislation this practice
      is no longer a viable method of waste management. It is necessary to improve
      existing and develop new sludge management techniques and one promising
      alternative is the dewatering and treatment of sludge in constructed wetlands.
      The aim of this study was to follow reduction of organic carbon, BOD and
      nutrients in an industrial sludge containing nitro-aromatic compounds passing
      through constructed small-scale wetlands, and to investigate any toxic effect
      such as growth inhibition of the common reed Phragmites australis. The result
      showed high reduction of all tested parameters in all the outgoing water samples,
      which shows that constructed wetlands are suitable for carbon and nutrient
      removal. The results also showed that P. australis is tolerant to xenobiotics and
      did not appear to be affected by the toxic compounds in the sludge. The sludge
      residual on the top of the beds contained low levels of organic carbon and is
      considered non-organic and could therefore be landfilled. Using this type of
      secondary treatment method, the amount of sludge could be reduced by 50-70%,
      mainly by dewatering and biodegradation of organic compounds.

PMID- 21944875
TI  - Use of thermal analysis techniques (TG-DSC) for the characterization of diverse
      organic municipal waste streams to predict biological stability prior to land
      application.
AB  - The use of organic municipal wastes as soil amendments is an increasing practice
      that can divert significant amounts of waste from landfill, and provides a
      potential source of nutrients and organic matter to ameliorate degraded soils.
      Due to the high heterogeneity of organic municipal waste streams, it is difficult
      to rapidly and cost-effectively establish their suitability as soil amendments
      using a single method. Thermal analysis has been proposed as an evolving
      technique to assess the stability and composition of the organic matter present
      in these wastes. In this study, three different organic municipal waste streams
      (i.e., a municipal waste compost (MC), a composted sewage sludge (CS) and a
      thermally dried sewage sludge (TS)) were characterized using conventional and
      thermal methods. The conventional methods used to test organic matter stability
      included laboratory incubation with measurement of respired C, and spectroscopic
      methods to characterize chemical composition. Carbon mineralization was measured
      during a 90-day incubation, and samples before and after incubation were analyzed
      by chemical (elemental analysis) and spectroscopic (infrared and nuclear magnetic
      resonance) methods. Results were compared with those obtained by thermogravimetry
      (TG) and differential scanning calorimetry (DSC) techniques. Total amounts of
      CO(2) respired indicated that the organic matter in the TS was the least stable,
      while that in the CS was the most stable. This was confirmed by changes detected
      with the spectroscopic methods in the composition of the organic wastes due to C
      mineralization. Differences were especially pronounced for TS, which showed a
      remarkable loss of aliphatic and proteinaceous compounds during the incubation
      process. TG, and especially DSC analysis, clearly reflected these differences
      between the three organic wastes before and after the incubation. Furthermore,
      the calculated energy density, which represents the energy available per unit of
      organic matter, showed a strong correlation with cumulative respiration. Results
      obtained support the hypothesis of a potential link between the thermal and
      biological stability of the studied organic materials, and consequently the
      ability of thermal analysis to characterize the maturity of municipal organic
      wastes and composts.

PMID- 21944876
TI  - Dynamic response of UV-absorbing compounds, quantum yield and the xanthophyll
      cycle to diel changes in UV-B and photosynthetic radiations in an aquatic
      liverwort.
AB  - We studied the diel responses of the liverwort Jungermannia exsertifolia subsp.
      cordifolia to radiation changes under laboratory conditions. The samples were
      exposed to three radiation regimes: P (only PAR), PA (PAR+UV-A), and PAB (PAR+UV
      A+UV-B). The day was divided in four periods: darkness, a first low-PAR period,
      the high-PAR plus UV period, and a second low-PAR period. After 15 days of
      culture, we measured photosynthetic pigments, chlorophyll fluorescence and UV
      absorbing compounds in the four periods of the day on two consecutive days. With
      respect to UV-absorbing compounds, we analyzed their global amount (as the bulk
      UV absorbance of methanolic extracts) and the concentration of seven
      hydroxycinnamic acid derivatives, both in the soluble (mainly vacuolar) and
      insoluble (cell wall-bound) fractions of the plant extracts. PAB samples
      increased the bulk UV absorbance of the soluble and insoluble fractions, and the
      concentrations of p-coumaroylmalic acid in the soluble fraction and p-coumaric
      acid in the cell wall. Most of these variables showed significant diel changes
      and responded within a few hours to radiation changes (more strongly to UV-B),
      increasing at the end of the period of high-PAR plus UV. F(v)/F(m), Phi(PSII),
      NPQ and the components of the xanthophyll cycle showed significant and quick diel
      changes in response to high PAR, UV-A and UV-B radiation, indicating dynamic
      photoinhibition and protection of PSII from excess radiation through the
      xanthophyll cycle. Thus, the liverwort showed a dynamic protection and
      acclimation capacity to the irradiance level and spectral characteristics of the
      radiation received.

PMID- 21944877
TI  - The interdependency of peak pressure and pressure-time integral in pressure
      studies on diabetic footwear: no need to report both parameters.
AB  - BACKGROUND: In plantar pressure studies on diabetic footwear, both the maximum
      peak pressure (MPP) and peak pressure-time integral (PTI) are often reported.
      However, specific conclusions for each parameter are not commonly reported,
      suggesting these parameters may be interchangeable. The aim was to explore the
      interdependency of MPP and PTI in diabetic patients wearing different types of
      footwear. METHODS: In-shoe plantar pressure was measured in 69 neuropathic
      diabetic patients who walked in custom made footwear, forefoot offloading shoes,
      cast shoes, and/or standard footwear. For each of six anatomical foot regions,
      correlation coefficients were calculated between MPP and PTI. To assess parameter
      congruency, the percentage of patients showing correlation coefficients >0.7 or
      coefficients of variation for both MPP and PTI <10%, was calculated. RESULTS:
      Across all footwear conditions, MPP and PTI were highly correlated in the
      forefoot and midfoot (r>0.78 in all but one foot region in one footwear
      condition). Lower correlations coefficients were found in the rearfoot (r=0.43
      0.45). Across regions, between 46% and 87% of patients (mean 72%) showed
      parameter congruency in the forefoot and midfoot. CONCLUSIONS: The results showed
      that the MPP and PTI are highly interdependent in those foot regions most at risk
      for plantar ulceration in patients wearing commonly prescribed footwear. Since
      MPP has been shown to date to be the clinically more relevant parameter of the
      two, these results suggest that the value of reporting PTI in addition to MPP in
      the same diabetic footwear study is small.

PMID- 21944878
TI  - S100-B protein as a screening tool for the early assessment of minor head injury.
AB  - STUDY OBJECTIVE: A computed tomography (CT) scan has high sensitivity in
      detecting intracranial injury in patients with minor head injury but is costly,
      exposes patients to high radiation doses, and reveals clinically relevant lesions
      in less than 10% of cases. We evaluate S100-B protein measurement as a screening
      tool in a large population of patients with minor head injury. METHODS: We
      conducted a prospective observational study in the emergency department of a
      teaching hospital (Bordeaux, France). Patients with minor head injury (2,128)
      were consecutively included from December 2007 to February 2009. CT scans and
      plasma S100-B levels were compared for 1,560 patients. The main outcome was to
      evaluate the diagnostic value of the S100-B test, focusing on the negative
      predictive value and the negative likelihood ratio. RESULTS: CT scan revealed
      intracranial lesions in 111 (7%) participants, and their median S100-B protein
      plasma level was 0.46 MUg/L (interquartile range [IQR] 0.27 to 0.72) versus 0.22
      MUg/L (IQR 0.14 to 0.36) in the other 1,449 patients. With a cutoff of 0.12
      MUg/L, traumatic brain injuries on CT were identified with a sensitivity of 99.1%
      (95% confidence interval [CI] 95.0% to 100%), a specificity of 19.7% (95% CI
      17.7% to 21.9%), a negative predictive value of 99.7% (95% CI 98.1% to 100%), a
      positive likelihood ratio of 1.24 (95% CI 1.20 to 1.28), and a negative
      likelihood ratio of 0.04 (95% CI 0.006 to 0.32). CONCLUSION: Measurement of
      plasma S100-B on admission of patients with minor head injury is a promising
      screening tool that may be of help to support the clinician's decision not to
      perform CT imaging in certain cases of low-risk head injury.

PMID- 21944879
TI  - Medical decisionmaking: let's not forget the physician.

PMID- 21944880
TI  - Feasibility and observed safety of interactive video games for physical
      rehabilitation in the intensive care unit: a case series.
AB  - BACKGROUND: Early rehabilitation in the intensive care unit (ICU) improves
      patients' physical function. Despite reports of using commercially available
      interactive video game systems for rehabilitation, there are few data evaluating
      feasibility and safety as part of routine in-patient rehabilitation, particularly
      in the ICU. METHODS: We conducted an observational study from September 1, 2009,
      to August 31, 2010, of adults admitted to a 16-bed medical ICU receiving video
      games as part of routine physical therapy (PT), evaluating use and indications
      and occurrence of 14 prospectively monitored safety events. RESULTS: Of 410
      patients receiving PT in the medical ICU, 22 (5% of all patients; male, 64%;
      median age, 52 years) had 42 PT treatments with video games (median
      [interquartile range] per patient, 1.0 [1.0-2.0]). Main indications for video
      game therapy included balance (52%) and endurance (45%), and the most common
      activities included boxing (38%), bowling (24%), and balance board (21%). Of 42
      treatments, 69% occurred while standing and 45% while mechanically ventilated.
      During 35 hours of PT treatment, 0 safety events occurred (95% upper confidence
      limit for safety event rate, 8.4%). CONCLUSIONS: Novel use of interactive video
      games as part of routine PT in critically ill patients is feasible and appears
      safe in our case series. Video game therapy may complement existing
      rehabilitation techniques for ICU patients.

PMID- 21944881
TI  - Nonspecific low back pain: assessment of available medications.
AB  - Many medications have been evaluated for the treatment of nonspecific low back
      pain. The only medications proven to be more effective than a placebo in chronic
      low back pain are nonsteroidal antiinflammatory drugs (NSAIDs), the acetaminophen
      tramadol combination, antidepressants other than selective serotonin reuptake
      inhibitors, and some types of spinal applications of glucocorticoids or local
      anesthetics. However, the efficacy of these drugs in inducing pain relief is
      limited, and NSAIDs are the only drugs that also improve function. Nevertheless,
      the outcome of nonspecific low back pain is favorable in most cases, even in
      placebo-treated patients. In addition, treatment effects vary dramatically across
      studies. One factor in this variability is the heterogeneity of patient
      populations. To improve the uniformity of patient populations enrolled in
      therapeutic trials, the selection criteria should take into account the
      nociceptive, dysfunctional, and possible neuropathic components of the pain
      syndrome.

PMID- 21944882
TI  - The Mini-Social Phobia Inventory: psychometric properties in an adolescent
      general population sample.
AB  - BACKGROUND: Onset of social phobia (SP) typically occurs in adolescence. Short
      screening instruments for its assessment are needed for use in primary health and
      school settings. The 3-item Mini-Social Phobia Inventory (SPIN) has demonstrated
      effectiveness in screening for generalized SP (GSP) in adults. This study
      examined the psychometrics of the Mini-SPIN in an adolescent general population
      sample. METHODS: Three hundred fifty adolescents aged 12 to 17 years were
      clinically interviewed using the Schedule for Affective Disorders and
      Schizophrenia for School-Age Children-Present and Lifetime Version for
      identification of SP and other Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition, Axis I disorders, blind to their Mini-SPIN status.
      Associations between SP; subclinical SP; other anxiety, depressive, and
      disruptive disorders; and Mini-SPIN scores were examined, and diagnostic
      efficiency statistics were calculated. The association between Mini-SPIN scores
      and the generalized subtype of SP was also examined. RESULTS: As in adults, the
      Mini-SPIN items differentiated subjects with SP from those without. A score of 6
      points or greater was found optimal in predicting SP with a sensitivity of 86%,
      specificity of 84%, and positive and negative predictive values of 26% and 99%.
      The Mini-SPIN also possessed discriminative validity, as scores were higher for
      adolescents with SP than they were for those with depressive, disruptive, and
      other anxiety disorders. The Mini-SPIN was also able to differentiate adolescents
      with GSP from the rest of the sample. CONCLUSIONS: The Mini-SPIN has good
      psychometrics for screening SP in adolescents from general population and may
      have value in screening for GSP.

PMID- 21944883
TI  - Adult phenylketonuria outcome and management.
AB  - The problem to evaluate treatment outcome in adult PKU (phenylketonuric) patients
      lies in the heterogeneity of the adult PKU population. This heterogeneity is not
      only based on the different treatment history of every individual patient but
      also on the different severity of the underlying defect of the enzyme
      phenylalanine hydroxylase. Recent, partly double blind studies in adult PKU
      patients further support recommendation for lifelong treatment. However, it has
      become evident that dietary treatment is suboptimal and continuation to adulthood
      often not accepted. Late detected PKU patients (up to 4-6 years of age) benefit
      from strict dietary treatment and are able to catch up in intellectual
      performance. Untreated, severely retarded patients with behavioral changes may
      benefit from introduction of dietary treatment. However, individual decision is
      necessary and based on the personal situation of the patient. In early and well
      treated patients a number of studies have demonstrated that cognitive and
      neurosychologic tests are different from controls. In addition there is evidence
      that patients with higher blood phenylalanine (phe) levels demonstrate more often
      psychiatric symptoms like depression and anxiety. Medical problems are more often
      observed: there are certain risks as impaired growth, decreased bone mineral
      density and nutrional deficits probably caused by dietary treatment with an
      artificial protein substitute and/or missing compliance with an unpleasant diet.
      The long term risk of a strict dietary treatment must be balanced with the risk
      of higher blood phe (mean blood phenylalanine >600-900 MUmol/L) on cognitive and
      neuropsychological functions and psychiatric symptoms. Further studies should
      consider the role of blood phe exposure for brain development in childhood and
      for brain function in all ages. Besides mean blood phe, fluctuation of blood phe
      over time is important. Fluctuation of blood phe is decreased by sapropterin
      treatment in responsive patients which would on the long term may have positive
      effects on cognitive outcome. Further studies also should include adult PKU
      patients.

PMID- 21944885
TI  - Elevated plasma pentraxin 3: a potential cardiovascular risk factor?
AB  - Cardiovascular disease (CVD) is still a primary cause of death in most countries.
      The pathogenesis of CVD can be influenced by multiple risk factors. Recent
      studies suggested that the innate immune system may be involved in the
      development of CVD. Pentraxins are critical components of the innate immune
      system. Recent researches have demonstrated that elevated plasma pentraxin 3
      (PTX3) is associated with cardiovascular events and cardiovascular risk factors.
      Thus, we hypothesized that elevated plasma PTX3 is a potential cardiovascular
      risk factor evidenced by the following aspects: (1) PTX3 inhibited angiogenesis
      and promoted restenosis, (2) the expression of PTX3 increased in advanced
      atherosclerotic lesions and the blood of patients with ischemic heart disorders,
      (3) elevated plasma PTX3 levels were associated with adverse cardiovascular
      outcomes. If the hypothesis is confirmed, PTX3 will be an effective target point
      to the prevention and treatment of CVD.

PMID- 21944884
TI  - Pathogenesis of aortic dilatation in mucopolysaccharidosis VII mice may involve
      complement activation.
AB  - Mucopolysaccharidosis VII (MPS VII) is due to mutations within the gene encoding
      the lysosomal enzyme beta-glucuronidase, and results in the accumulation of
      glycosaminoglycans. MPS VII causes aortic dilatation and elastin fragmentation,
      which is associated with upregulation of the elastases cathepsin S (CtsS) and
      matrix metalloproteinase 12 (MMP12). To test the role of these enzymes, MPS VII
      mice were crossed with mice deficient in CtsS or MMP12, and the effect upon
      aortic dilatation was determined. CtsS deficiency did not protect against aortic
      dilatation in MPS VII mice, but also failed to prevent an upregulation of
      cathepsin enzyme activity. Further analysis with substrates and inhibitors
      specific for particular cathepsins suggests that this enzyme activity was due to
      CtsB, which could contribute to elastin fragmentation. Similarly, MMP12
      deficiency and deficiency of both MMP12 and CtsS could not prevent aortic
      dilatation in MPS VII mice. Microarray and reverse-transcriptase real-time PCR
      were performed to look for upregulation of other elastases. This demonstrated
      that mRNA for complement component D was elevated in MPS VII mice, while
      immunostaining demonstrated high levels of complement component C3 on surfaces
      within the aortic media. Finally, we demonstrate that neonatal intravenous
      injection of a retroviral vector encoding beta-glucuronidase reduced aortic
      dilatation. We conclude that neither CtsS nor MMP12 are necessary for elastin
      fragmentation in MPS VII mouse aorta, and propose that CtsB and/or complement
      component D may be involved. Complement may be activated by the GAGs that
      accumulate, and may play a role in signal transduction pathways that upregulate
      elastases.

PMID- 21944886
TI  - Transfer of the amyloid beta and/or of beta-amyloid precursor protein of the
      fetus with trisomy 21 to the maternal blood stream and its possible contribution
      to the pathogenesis of the maternal Alzheimer's Disease.
AB  - Down Syndrome (DS) is the most frequent genetic pathology. It affects 1 out of
      every 800 newborn babies. Approximately between a 90% and a 95% of all the cases
      of DS are attributed to a trisomy in chromosome 21. One of the genes contained in
      this chromosome is the gene of beta-amyloid precursor protein (betaAPP). The
      metabolism of this protein yields, among others, the amyloid beta peptides made
      up of 40 amino acids (Abeta40) and 42 amino acids (Abeta42). The evidence that is
      derived from several sources--genetic, among them--suggests that the Abeta
      participates in the pathogenesis of Alzheimer's Disease (AD). It is worth
      pointing at the fact that the transfer of cells, extracellular chromosomal
      material and some proteins from the fetus to the mother and vice versa has been
      widely described. The transfer rate from the fetus to the mother is higher when
      the mother is carrying a baby with trisomy 21. This has led to the hypothesis
      that sets forth that during the gestation of a baby with DS there is a greater
      fetomaternal transfer of cells and of products of the genes of chromosome 21-
      among them, betaAPP and its metabolites Abeta40 and Abeta42. It is possible to
      speculate on the possible contribution of the fetal components--among them, Abeta
      -to the higher risk of suffering AD, which has been reported in a subpopulation
      of women who have given birth to children with DS. On the other hand, the
      detection of the betaAPP--mainly intracellular--and of the beta amyloid peptides
      in maternal blood and urine during the early stages of gestation could be taken
      as a potential non invasive biochemical prenatal marker of DS.

PMID- 21944887
TI  - Olfactory and tissue markers of fear in mammals including humans.
AB  - Pheromones are a mysterious world of chemical signals involved in conspecific
      communication. They play a number of key functions important for preservation of
      life of individual organisms, for their defence, survival of offspring and
      preservation of species. The best-known groups of pheromones include: trail
      pheromones, territorial pheromones, sex pheromones, aggregation pheromones,
      dispersion pheromones, repellent pheromones, social pheromones and alarm
      pheromones. Alarm pheromones are pheromones that are emitted by animals in
      threatening situations and inform members of the same species of danger. The
      identified alarm pheromones are synthesised by insects and aquatic organisms.
      Also humans are able to emit and perceive pheromones. Although alarm pheromones
      have not been isolated and identified in man so far, there is presumably evidence
      for their presence in humans. Pinpointing human alarm pheromones, determinants of
      experienced stress and inductors of provoked fear could have widespread
      consequences. Their identification could also be of significant importance for
      the practical utilisation of results by institutions responsible for safety and
      defence as well as law enforcement/crime detection and antiterrorist activities.

PMID- 21944888
TI  - Melatonin and zinc treatment: distinctive modulation of cytokine production in
      chronic experimental Trypanosoma cruzi infection.
AB  - Melatonin by exhibiting antioxidant, anti-aging, and immunomodulatory properties
      favorably modulate the immune function, protecting the hosts from several
      infectious diseases. Zinc is an essential trace element important for the
      efficiency of the immune system in reason of its widespread role in the activity
      of enzymes, transcription factors and cytokines. The etiology of Chagas' disease,
      caused by a protozoan parasite Trypanosoma cruzi, has been the focus of
      considerable discussion, although chronic phase still remains not fully
      understood. This study showed that zinc and melatonin treatment did not affect
      the percentage of both CD4+ and CD8+ T lymphocytes subsets in chronically
      infected animals. Increased levels of IL-2 and IL-10, as well as, enhanced
      thymocyte proliferation in T. cruzi infected groups under zinc and melatonin
      therapy was observed as compared to untreated group. Conversely, during the
      chronic phase of infection, macrophages counts were reduced in melatonin and zinc
      melatonin treated animals. The combined actions of zinc and melatonin have
      beneficial effects in counteracting parasite-induced immune dysregulation,
      protecting animals against the harmful actions of chronic T. cruzi infection.
      Furthermore, our results provide an experimental basis for further studies on the
      role of immunomodulatory therapies.

PMID- 21944889
TI  - Naive CD4+ T cells of Peyer's patches produce more IL-6 than those of spleen in
      response to antigenic stimulation.
AB  - Peyer's patches (PPs) are potential sites where specific mucosal immune responses
      and oral tolerance are induced. The unique features of these immune responses are
      thought to occur in micromilieu and are largely affected by antigen-presenting
      cells (APCs) such as dendritic cells. In this study, we investigated the cytokine
      profiles induced by the activation of CD4(+) T cells of PPs. PP cells from TCR
      transgenic mice secreted greater amounts of IL-5 and IL-6 than spleen cells after
      antigenic stimulation. IL-5 was mainly produced by PP non-T cells, whereas IL-6
      was secreted by PP CD4(+) cells. PPs contained two major populations including
      naive and memory/activated CD4(+) cells; both populations secreted IL-6 upon
      activation. We also found that CD4(+)/CD62L(hi) naive cells from PPs secreted a
      greater amount of IL-6 after stimulation than those from the spleen. Furthermore,
      subtraction and qPCR analyses revealed that PP CD4(+)/CD62L(hi) cells express a
      greater amount of transcripts of GA-binding protein beta subunit 1 than those of
      the spleen. These results suggest that naive T cells as well as non-T cells and
      activated/memory T cells from PPs are distinct from their splenic counterparts
      and thus cause unique immune responses the in intestine.

PMID- 21944890
TI  - miRNA-451: A putative predictor marker of Imatinib therapy response in chronic
      myeloid leukemia.

PMID- 21944891
TI  - The relative lung and systemic bioavailability of terbutaline following
      nebulisation in non-invasively ventilated patients.
AB  - Nebulising a bronchodilator during non-invasive ventilation (NIV) is effective
      but there is a lack of consensus on the system to use because comparator in vivo
      studies in these patients are difficult. Urinary pharmacokinetic methodology post
      inhalation could provide this information. Chronic obstructive pulmonary disease
      patients requiring NIV received randomised study doses of either 2mg terbutaline
      nebulised from an Aeroneb Pro (AERO) or 5mg from a Sidestream (SIDE) on days 1
      and 3 of admission. Urine samples were provided at 30 min then pooled up to 24h
      post inhalation and amounts of urinary terbutaline (UTER0.5 and UTER24; indices
      of relative lung and systemic bioavailability, respectively) were determined.
      Twelve consenting patients receiving NIV mean (SD) age and weight of 74.8 (8.2)
      years and 61.0 (10.7)kg completed the study. The mean (SD) UTER0.5 following AERO
      and SIDE was 9.4 (3.7) and 10.4 (4.1) MUg with a mean ratio (90% confidence
      interval) of 89.7 (87.8, 92.3)%. UTER24 was 192.3 (52.4) and 205.3 (58.0)mcg with
      a mean ratio (90% CI) of 93.7 (113.5, 77.3)%. This urinary pharmacokinetic method
      to identity relative lung and systemic bioavailability between two nebuliser
      systems was easy to perform and is a useful and simple in vivo method to compare
      different nebulisers in patients receiving non-invasive ventilation.

PMID- 21944892
TI  - Comparison of solid self-microemulsifying drug delivery system (solid SMEDDS)
      prepared with hydrophilic and hydrophobic solid carrier.
AB  - In order to compare the effects of hydrophilic and hydrophobic solid carrier on
      the formation of solid self-microemulsifying drug delivery system (SMEDDS), two
      solid SMEDDS formulations were prepared by spray-drying the solutions containing
      liquid SMEDDS and solid carriers. Colloidal silica and dextran were used as a
      hydrophobic and a hydrophilic carrier, respectively. The liquid SMEDDS, composed
      of Labrafil M 1944 CS/Labrasol/Trasncutol HP (12.5/80/7.5%) with 2% w/v
      flurbiprofen, gave a z-average diameter of about 100 nm. Colloidal silica
      produced an excellent conventional solid SMEDDS in which the liquid SMEDDS was
      absorbed onto its surfaces. It gave a microemulsion droplet size similar to that
      of the liquid SMEDDS (about 100 nm) which was smaller than the other solid SMEDDS
      formulation. In the solid SMEDDS prepared with dextran, liquid SMEDDS was not
      absorbed onto the surfaces of carrier but formed a kind of nano-sized
      microcapsule with carrier. However, the drug was in an amorphous state in two
      solid SMEDDS formulations. Similarly, they greatly improved the dissolution rate
      and oral bioavailability of flurbiprofen in rats due to the fast spontaneous
      emulsion formation and the decreased droplet size. Thus, except appearance,
      hydrophilic carrier (dextran) and hydrophobic carrier (colloidal silica) hardly
      affected the formation of solid SMEDDS such as crystalline properties,
      dissolution and oral bioavailability.

PMID- 21944893
TI  - Diffusion tensor imaging of subependymal heterotopia.
AB  - A magnetic resonance (MR) diffusion tensor imaging (DTI) study was performed in a
      newborn with bilateral subependymal heterotopia (SE). White matter fractional
      anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD) were compared
      to values obtained in four newborns with moderate perinatal asphyxia and normal
      MRI findings. The reduction of FA and increase of AD and RD in the newborn with
      SE were the in vivo late expression of alterations in the intermediate zone, with
      an underlying arrest of neuronal migration.

PMID- 21944894
TI  - Levetiracetam clinical pharmacokinetics in elderly and very elderly patients with
      epilepsy.
AB  - We aimed to compare apparent steady-state oral clearance (CL/F) of the
      antiepileptic drug levetiracetam (LEV) in elderly (66-80 years, n=105) and very
      elderly (81-96 years, n=70) vs nonelderly (30-65 years, n=97) patients with
      epilepsy. Median weight-normalized CL/F (mLmin(-1)kg(-1)) decreased from 1.23
      (nonelderly) to 0.83 (elderly) and 0.59 (very elderly) (p<0.001). LEV CL/F
      significantly declines with aging, elderly and very elderly patients requiring an
      about 30% and 50% lower dose, respectively, compared to nonelderly adults to
      achieve a given LEV plasma concentration.

PMID- 21944895
TI  - Interactions of pregabalin with gabapentin, levetiracetam, tiagabine and
      vigabatrin in the mouse maximal electroshock-induced seizure model: a type II
      isobolographic analysis.
AB  - The aim of this study was to characterize the anticonvulsant effects of
      pregabalin in combination with four second-generation antiepileptic drugs (i.e.,
      gabapentin, levetiracetam, tiagabine, and vigabatrin) in the mouse maximal
      electroshock (MES)-induced seizure model by using the type II isobolographic
      analysis. Tonic hind limb extension (seizure activity) was evoked in adult male
      albino Swiss mice by a current (sine-wave, 25 mA, 500 V, 50 Hz, 0.2 s stimulus
      duration) delivered via auricular electrodes. The combination of pregabalin with
      gabapentin at the fixed-ratio of 1:1 was supra-additive (synergistic) in terms of
      seizure suppression while the combinations at the fixed-ratios of 2:1 and 4:1
      were additive in the mouse MES model. Similarly, the combination of pregabalin
      with tiagabine at the fixed-ratio of 25:1 was supra-additive, whereas the
      combinations at the fixed-ratios of 100:1 and 50:1 were additive in the mouse MES
      model. Pregabalin with levetiracetam and vigabatrin at the fixed-ratios of 1:1,
      2:1 and 4:1 were additive in this seizure model. The combinations of pregabalin
      with gabapentin (1:1) and pregabalin with tiagabine (25:1) appear to be favorable
      combinations exerting supra-additive interaction in suppressing MES-induced
      seizures. Pregabalin in combination with levetiracetam and vigabatrin appears to
      be neutral producing only additivity in the mouse MES model.

PMID- 21944896
TI  - [A study of tuberculosis infection in workers at a university general hospital:
      associated factors and evolution in 20 years].
AB  - OBJECTIVE: To estimate the prevalence of tuberculous infection (TI) in the health
      care workers of a hospital over the course of a 20-year period and analyze the
      associated risk factors. SUBJECTS AND METHODS: A cross-sectional, descriptive
      study of the workers of a general hospital from 1988 until 2007, using a
      tuberculin test (TT) and questionnaire. RESULTS: 2,179 workers were studied (mean
      age 32.4 years (SD 8.4). 24.5% worked in areas at risk for tuberculosis (TB).
      8.1% (174) were vaccinated with BCG. The prevalence of positive baseline TT was
      25.7% (95% confidence interval: 23.8-27.4%). There was a greater percentage of
      positive TT in the 1988-1992 period (44.2%) and a smaller percentage (15.8%) in
      the 2003-2007 period (P<.0001). The prevalence of TI was 1.53 times greater in
      males and 1.89 in those vaccinated with BCG. When compared with resident
      physicians, the prevalence of TI was greater in the rest of the professional
      categories, while increasing 1.03 times per year that age increases and 1.05
      times per year of professional activity. CONCLUSIONS: The data provide relevant
      information about the evolution of TI in hospital professionals over the course
      of a 20-year period. The prevalence decreased during the study period, probably
      due to a decrease in the incidence of TB in the reference community and to
      improved prevention measures and nosocomial control.

PMID- 21944897
TI  - Process without progress: emergency medicine, patient safety, and the need for
      science.

PMID- 21944898
TI  - Emergency medicine simulation: a resident's perspective.

PMID- 21944899
TI  - How accurately do pneumonia severity scores predict mortality in patients with
      community-acquired pneumonia?

PMID- 21944900
TI  - Rapid isolation procedure for Delta9-tetrahydrocannabinolic acid A (THCA) from
      Cannabis sativa using two flash chromatography systems.
AB  - Two isolation procedures for Delta9-tetrahydrocannabinolic acid A (THCA), the
      biogenetic precursor in the biosynthesis of the psychoactive Delta9
      tetrahydrocannabinol (THC) in the cannabis plant, are presented. Two flash
      chromatography systems that can be used independently from each other were
      developed to separate THCA from other compounds of a crude cannabis extract. In
      both systems UV absorption at 209 and 270 nm was monitored. Purity was finally
      determined by HPLC-DAD, NMR and GC-MS analysis with a focus on the impurity THC.
      System 1 consisted of a normal phase silica column (120 g) as well as cyclohexane
      and acetone--both spiked with the modifier pyridine--as mobile phases. Gradient
      elution was performed over 15 min. After the chromatographic run the fractions
      containing THCA fractions were pooled, extracted with hydrochloric acid to
      eliminate pyridine and evaporated to dryness. Loading 1800 mg cannabis extract
      yielded 623 mg THCA with a purity of 99.8% and a THC concentration of 0.09%.
      System 2 was based on a reversed-phase C18 column (150 g) combined with 0.55%
      formic acid and methanol as mobile phases. A very flat gradient was set over 20
      minutes. After pooling the THCA-containing fractions methanol was removed in a
      rotary evaporator. THCA was re-extracted from the remaining aqueous phase with
      methyl tert-butyl ether. The organic phase was finally evaporated under high
      vacuum conditions. Loading 300 mg cannabis extract yielded 51 mg THCA with a
      purity of 98.8% and a THC concentration of 0.67%.

PMID- 21944901
TI  - Bimolane induces multiple types of chromosomal aberrations in human lymphocytes
      in vitro.
AB  - Bimolane has been commonly used in China for the treatment of psoriasis and
      various types of cancer. Patients treated with bimolane have been reported to
      have an increased risk of developing therapy-related leukemias. Although bimolane
      has been identified as a human leukemia-inducing agent, little is known about its
      genotoxic effects, and a systematic study of the types of chromosomal alterations
      induced by this compound has not been performed. In this study, a combination of
      immunochemical, molecular and conventional cytogenetic techniques has been used
      to study the chromosomal alterations induced by bimolane in cultured human
      lymphocytes. Immunochemical staining with the CREST antibody indicated that
      bimolane induces micronuclei (MN) originating primarily from chromosome breakage.
      Interestingly fluorescence in situ hybridization (FISH) with differentially
      labeled chromosomes 1 and 9 centromeric probes indicated that bimolane also
      caused non-disjunction and polyploidy. Consistent with this, an expedited
      analysis of Giemsa-stained metaphase chromosomes in bimolane-treated lymphocytes
      revealed a high frequency of polyploidy/hyperdiploidy as well as dicentric
      chromosomes, and premature centromeric division (PCD). In addition, bimolane was
      also found to produce binucleated cells, possibly through an interference with
      normal functioning of intermediate filaments. As a follow-up to these studies,
      three different types of commercially available bimolane formulations obtained
      from different Chinese manufacturers were also evaluated. The effects seen with
      the formulated bimolane were similar to those seen with the synthesized compound.
      Our studies indicate that bimolane effectively induces a variety of cellular and
      chromosomal changes in cultured lymphocytes and that similar alterations
      occurring in bone marrow stem cells could contribute to the development of the
      secondary cancers seen in bimolane-treated patients.

PMID- 21944902
TI  - Ganoderma lucidum total triterpenes prevent radiation-induced DNA damage and
      apoptosis in splenic lymphocytes in vitro.
AB  - The development of radioprotective agents has been the subject of intense
      research, especially in the field of radiotherapy. In this study, we examined the
      radioprotective activity of the total triterpenes isolated from Ganoderma lucidum
      (Fr.) P. Karst in mouse splenic lymphocytes in vitro. Using the MTT assay,
      Ganoderma triterpenes were found to have no effect on cell viability, indicating
      that they are non-toxic to splenic lymphocytes. The effect of the total
      triterpenes on DNA damage and apoptosis induced by radiation was analyzed using
      the comet assay, DNA ladder assay and flow cytometric analysis. Total triterpenes
      were found to be highly effective in preventing DNA laddering, even at low
      concentrations (25MUg/ml). The comet assay demonstrated that the G. triterpenes
      effectively prevented DNA damage, and flow cytometry revealed a reduction in
      apoptotic cells. The effect of the total triterpenes on intracellular reactive
      oxygen species (ROS) level and endogenous antioxidant enzyme activity in splenic
      lymphocytes were determined to elucidate possible radioprotective mechanisms.
      Total triterpenes successfully reduced the formation of intracellular ROS and
      enhanced endogenous antioxidant enzyme activity in splenic lymphocytes following
      irradiation. Thus, these findings indicate that the total triterpenes isolated
      from G. lucidum have a remarkable ability to protect normal cells from radiation
      induced damage, which suggests therapeutic potential.

PMID- 21944903
TI  - DNA damage in patients who underwent minimally invasive surgery under inhalation
      or intravenous anesthesia.
AB  - Recent studies have demonstrated the genotoxicity of anesthetics in patients who
      have undergone surgery and in personnel who are occupationally exposed to
      anesthetics. However, these findings are controversial. Herein, we used the comet
      assay (single-cell gel electrophoresis) to investigate the genotoxic effects of
      two volatile compounds [isoflurane (ISF) and sevoflurane (SVF)] that are used in
      inhalation anesthesia, and of one intravenous (iv) anesthetic compound [propofol
      (PF)]. The groups consisted of 45 patients who underwent minimally invasive
      surgery that lasted at least 2h. Patients were classified as physical status I
      using the criteria of the American Society of Anesthesiologists (ASA) and were
      randomly allocated to receive ISF, SVF or PF anesthesia. Venous blood samples
      were collected at three time points as follows: before the premedication and the
      induction of anesthesia (T(0)); 2h after the beginning of anesthesia (T(1)); and
      on the day following surgery (T(2)). DNA damage (strand breaks and alkali-labile
      sites) was evaluated in peripheral blood lymphocytes. For each patient, one
      hundred nucleoids were analyzed per time point using a semi-automated image
      system. Patients did not differ with respect to their demographic
      characteristics, the duration of surgery, or the total doses of intraoperative
      drugs. The amount of DNA damage was not different among the three groups before
      anesthesia (T(0)). No statistically significant (p>0.05) increase in DNA damage
      was detected during (T(1)) or after anesthesia (T(2)) using three different
      protocols (ISF, SVF or PF). In conclusion, general anesthesia with inhaled ISF
      and SVF or iv PF did not induce DNA strand breaks or alkali-labile sites in
      peripheral lymphocytes. Therefore, our results show that the genotoxic risk of
      these anesthetics, for healthy patients undergoing minimally invasive
      otorhinological surgery, is low or even absent.

PMID- 21944904
TI  - Use of the in vivo skin comet assay to evaluate the DNA-damaging potential of
      chemicals applied to the skin.
AB  - The aim of the present study was to evaluate both sensitivity and specificity of
      an in vivo skin comet assay using chemically treated, hairless mouse dorsal skin
      as a model. N-methyl-N'-nitro-N-nitrosoguanidine (MNNG, 0.0125-0.2%), 4
      nitroquinoline-1-oxide (4NQO, 0.01-0.25%), mitomycin C (MMC, 0.0125-0.05%),
      benzo[a]pyrene (B[a]P, 0.25-2%), and 7,12-dimethylbenz[a]anthracene (DMBA, 0.25
      1%) were each applied once to the dorsal skin of hairless male mice; after 3h,
      epidermal skin cells were isolated, and the alkaline comet assay was performed.
      The assay was performed after 24h for only the B[a]P and DMBA. Furthermore, B[a]P
      and DMBA were evaluated by alkaline comet assay using liver cells after both 3
      and 24h. The mean percent of DNA (%DNA) in tail in the 0.05-0.2% MNNG and 0.1
      0.25% 4NQO treatment groups was markedly higher than in the control group at 3h
      post-application. Although the mean %DNA values in the tail in the B[a]P and DMBA
      groups were the same as the controls at 3h post-application, the 2% B[a]P and 1%
      DMBA groups showed significantly higher values versus controls 24h after
      application. No significant increases in the mean %DNA in the tail were observed
      in the MMC group. No clear increases in %DNA in the tail were observed in the
      B[a]P and DMBA groups at 3 or 24h after application in the liver. These results
      suggest that the in vivo skin comet assay is able to accurately identify DNA
      damaging potential with a skin-specific response and is a useful method to detect
      the DNA-damaging potential of genotoxic chemicals on the skin.

PMID- 21944905
TI  - Genotoxicity assessment of ethylenediamine dinitrate (EDDN) and
      diethylenetriamine trinitrate (DETN).
AB  - Ethylenediamine dinitrate (EDDN) and diethylenetriamine trinitrate (DETN) are
      relatively insensitive explosive compounds that are being explored as safe
      alternatives to other more sensitive compounds. When used in combination with
      other high explosives they are an improvement and may provide additional safety
      during storage and use. The genetic toxicity of these compounds was evaluated to
      predict the potential adverse human health effects from exposure by using a
      standard genetic toxicity test battery which included: a gene mutation test in
      bacteria (Ames), an in vitro Chinese Hamster Ovary (CHO) cell chromosome
      aberration test and an in vivo mouse micronucleus test. The results of the Ames
      test showed that EDDN increased the mean number of revertants per plate with
      strain TA100, without activation, at 5000MUg/plate compared to the solvent
      control, which indicated a positive result. No positive results were observed
      with the other tester strains with or without activation in Salmonella
      typhimurium strains TA98, TA1535, TA1537, and Escherichia coli strain WP2 uvrA.
      DETN was negative for all Salmonella tester strains and E. coli up to
      5000MUg/plate both with and without metabolic activation. The CHO cell chromosome
      aberration assay was performed using EDDN and DETN at concentrations up to
      5000MUg/mL. The results indicate that these compounds did not induce structural
      chromosomal aberrations at all tested concentrations in CHO cells, with or
      without metabolic activation. EDDN and DETN, when tested in vivo in the CD-1
      mouse at doses up to 2000mg/kg, did not induce any significant increase in the
      number of micronuclei in bone marrow erythrocytes. These studies demonstrate that
      EDDN is mutagenic in one strain of Salmonella (TA100) but was negative in other
      strains, for in vitro induction of chromosomal aberrations in CHO cells, and for
      micronuclei in the in vivo mouse micronucleus assay. DETN was not genotoxic in
      all in vitro and in vivo tests. These results show the in vitro and in vivo
      genotoxicity potential of these chemicals.

PMID- 21944906
TI  - Porphyromonas gingivalis antigens differently participate in the proliferation
      and cell death of human PBMC.
AB  - OBJECTIVE: Modulation of cell-mediated immunity by microorganisms in periodontal
      diseases has been widely studied; however, the proliferative activity and/or
      programmed death of mononuclear cells under periodontopathogenic stimuli are not
      yet well understood. The aim of this study was to investigate in vitro
      proliferation and death of peripheral blood mononuclear cells (PBMC) upon
      stimulation with Porphyromonas gingivalis (Pg) antigens. DESIGN: In 19 patients
      with chronic periodontitis (CP) and 16 controls without periodontitis (NP) the
      following clinical parameters were evaluated: bleeding on probing, probing depth,
      and clinical attachment level. PBMC were cultured under Pg stimuli and
      apoptosis/necrosis and proliferation assays were carried out for 18 and 48 h,
      respectively. Fluorescence of labelled cells was determined using flow cytometry.
      RESULTS: PBMC of CP and NP subjects exhibited a lower proliferative response to
      Pg LPS (p<0.05) and HmuY protein (p<0.001) compared with non-stimulated cells.
      Early apoptosis was induced by Pg LPS (p<0.01) and Pg extract (p<0.05), whilst
      all antigens induced late apoptosis (Pg LPS: p<0.001; Pg extract: p<0.001; HmuY:
      p<0.01) and necrosis (Pg LPS: p<0.01; Pg extract: p<0.001; HmuY: p<0.001). Pg LPS
      induced higher late apoptosis than HmuY (p<0.05). Only Pg LPS-induced necrosis
      tended to be higher in CP compared with NP. CONCLUSIONS: The inhibitory effect of
      cell proliferation caused by Pg LPS and HmuY protein is not observed when these
      antigens comprise Pg extract. Despite induced apoptosis, some still unknown
      mechanism determines the inflammatory outcome in cell death stimulated by HmuY.

PMID- 21944907
TI  - Endovascular treatment of acute aortic syndrome.
AB  - BACKGROUND: The term acute aortic syndrome (AAS) encompasses a range of
      conditions that have a risk of imminent aortic rupture and where delays in
      treatment result in increased mortality. Endovascular treatment offers an
      attractive alternative to open surgery but little is known about the durability
      of the repair and the factors that predict mortality. METHODS: Prospective data
      were collected for a cohort of 110 consecutive patients with endovascular
      treatment for AAS. Patient and procedural characteristics were related to short-
      and midterm outcome using multivariate logistic regression analysis. RESULTS:
      There were 75 men and 35 women with a median age of 68 (range 57-76) years. The
      pathologies treated were acute dissection (35), symptomatic aneurysm (32),
      infected aneurysm (18), transection (12), chronic dissection (9), penetrating
      ulcer (3), and intramural hematoma (1). Thirty-day mortality was 12.7% and this
      was associated with hypotension (odds ratio [OR], 5.25), use of general
      anesthetic (OR, 5.23), long procedure duration (OR, 2.03), and increasing age
      (OR, 1.07). The causes of death were aortic rupture (4), myocardial infarction
      (4), stroke (3), and multisystem organ failure (3). The stroke and paraplegia
      rates were 7.3% and 6.4%, respectively. The 1-year survival was 81% and the 5
      year survival 63%. Secondary procedures were required in 13 (11.8%) patients.
      Factors associated with death at 1 year were presence of an aortic fistula (OR,
      9.78), perioperative stroke (OR, 5.87), and use of general anesthetic (OR, 3.76);
      and at 5 years were aortic fistula (OR, 12.31) and increasing age (OR, 1.06).
      CONCLUSIONS: Acute aortic syndrome carries significant early and late mortality.
      Emergency endovascular repair offers a minimally invasive treatment option
      associated with acceptable short and midterm results. Continued surveillance is
      important as secondary procedures and aortic-related deaths continue to occur
      throughout the follow-up period.

PMID- 21944909
TI  - Natural history of spontaneous isolated superior mesenteric artery dissection
      derived from follow-up after conservative treatment.
AB  - OBJECTIVES: Optimal treatment of spontaneous isolated superior mesenteric artery
      dissection (SISMAD) has not been established in part because the natural history
      of this rare vascular disease is not well established. We attempted to determine
      the natural history of SISMAD by observing patients who underwent conservative
      treatment. METHODS: Among 58 consecutive patients with SISMAD, 46 who underwent
      conservative treatment and periodic follow-up of computed tomography (CT)
      angiography (CTA) were included for this study. Our first-line treatment for
      SISMAD patients was conservative (n = 53), reserving interventional treatment,
      either endovascular (n = 1) or surgical (n = 4), for patients with persistent
      abdominal pain despite conservative treatment or signs of bowel ischemia. We
      retrospectively investigated changes of the length, type, or remodeling of the
      dissection and superior mesenteric artery patency on multidetector CT scan. To
      evaluate clinical course, presence of persistent or recurrent abdominal symptoms
      was queried on an outpatient base. RESULTS: After 23.0 (median, range 6.5-74.2)
      months, follow-up CT angiograms showed diminished extent of the false lumen size
      in 19 (41.3%), no change in 20 (43.5%), diminished length of dissection in 11
      (23.9%), and complete remodeling of dissection in seven (15.2%) patients. No
      patient showed dissection progression on follow-up angiogram. During the follow
      up period, 10 (26.3%) patients reported nonspecific, mild abdominal discomfort,
      however, no patient developed recurrent abdominal pain following conservative
      treatment. There was no mortality related with SISMAD. CONCLUSIONS: After
      conservative treatment of SISMAD, we have observed that the majority of patients
      showed improvement or no change on both angiogram and clinical examination. We
      believe this observation supports an approach of conservative treatment for
      patients with SISMAD.

PMID- 21944908
TI  - High mobility group box 1 promotes endothelial cell angiogenic behavior in vitro
      and improves muscle perfusion in vivo in response to ischemic injury.
AB  - OBJECTIVES: The angiogenic drive in skeletal muscle ischemia remains poorly
      understood. Innate inflammatory pathways are activated during tissue injury and
      repair, suggesting that this highly conserved pathway may be involved in ischemia
      induced angiogenesis. We hypothesize that one of the endogenous ligands for
      innate immune signaling, high mobility group box 1 (HMGB1), in combination with
      autophagic responses to hypoxia or nutrient deprivation, plays an important role
      in angiogenesis. METHODS: Human dermal microvascular endothelial cells (ECs) were
      cultured in normoxia or hypoxia (1% oxygen). Immunocytochemical analysis of HMGB1
      subcellular localization, evaluation of tube formation, and Western blot analysis
      of myotubule light-chain 3I (LC3I) conversion to LC3II, as a marker of autophagy,
      were conducted. 3-Methyladenine (3MA), chloroquine, or rapamycin were
      administered to inhibit or promote autophagy, respectively. In vivo, a murine
      hind limb ischemia model was performed. Muscle samples were collected at 4 hours
      to evaluate for nuclear HMGB1 and at 14 days to examine endothelial density.
      Perfusion recovery in the hind limbs was calculated by laser Doppler perfusion
      imaging (LDPI). RESULTS: Hypoxic ECs exhibited reduced nuclear HMGB1 staining
      compared with normoxic cells (mean fluorescence intensity, 186.9 +/- 17.1 vs
      236.0 +/- 1.6, P = .01) with a concomitant increase in cytosolic staining. HMGB1
      treatment of ECs enhanced tube formation, an angiogenic phenotype of ECs.
      Neutralization of endogenous HMGB1 markedly impaired tube formation and inhibited
      LC3II formation. Inhibition of autophagy with 3MA or chloroquine abrogated tube
      formation, whereas its induction with rapamycin enhanced tubing and promoted
      HMGB1 translocation. In vivo, ischemic skeletal muscle showed reduced numbers of
      HMGB1-positive myocyte nuclei compared with nonischemic muscle (34.9% +/- 1.9% vs
      51.7% +/- 2.0%, P < .001). Injection of HMGB1 into ischemic hind limbs increased
      perfusion recovery by 21% and increased EC density (49.2 +/- 4.1 vs 34.2 +/- 3.4
      ECs/high-powered field, respectively; P = .02) at 14 days compared with control
      hind limbs. CONCLUSIONS: Nuclear release of HMGB1 and autophagy occur in ECs in
      response to hypoxia or serum depletion. HMGB1 and autophagy are necessary and
      likely play an interdependent role in promoting the angiogenic behavior of ECs.
      In vivo, HMGB1 promotes perfusion recovery and increased EC density after
      ischemic injury. These findings suggest a possible mechanistic link between
      autophagy and HMGB1 in EC angiogenic behavior and support the importance of
      innate immune pathways in angiogenesis.

PMID- 21944910
TI  - Management and prognosis of nonpulmonary large arterial disease in patients with
      Behcet disease.
AB  - OBJECTIVE: The purpose of this study was to evaluate and report our treatment
      policies in the management of nonpulmonary arterial aneurysms in Behcet disease
      and to assess the prognosis in a cohort of 25 patients diagnosed between 1996 and
      2007 by formally reassessing their outcome at the present time. METHODS: We
      identified 25 patients (24 men/1 woman) with Behcet disease with nonpulmonary
      aneurysms (n = 23) or occlusions (n = 2) between 1996 and 2007. All patients
      fulfilled the International Study Group Criteria for Behcet disease. Aneurysms
      were demonstrated with contrast-enhanced computed tomography (CT) or magnetic
      resonance angiography (MRA) after first-line ultrasonography. Standard surgical
      procedures were carried out in 22 patients. One patient with a nonruptured
      saccular aortic aneurysm and 2 patients with carotid aneurysms were managed only
      medically. For the patients with aneurysms located in the aortic bifurcation, we
      preferred aorto-bi-iliac bypasses; for the six extremity aneurysms, we were able
      to ligate the arteries; and for the other 10 extremity aneurysms we used
      polytetrafluoroethylene (PTFE) grafts for bypass procedures. All patients
      received immunosuppression with cyclophosphamide and corticosteroids before the
      operation and were continued in the postoperative period. All patients were
      examined between January and December 2010 paying special attention for new and
      anastomotic aneurysms and graft patency. RESULTS: There was one death and 1
      patient was lost to follow-up. The remaining 23 patients (92%) were under follow
      up after a mean of 7.4 +/- 2.9 years after their operation. Four PTFE grafts
      (40%) inserted for extremity aneurysms occluded with no disabling consequences.
      Also, 6 patients who were treated with ligation postoperatively began to complain
      of mild to moderate claudication. In 2 patients, aneurysms recurred at the
      anastomotic site, whereas in 3 patients, new aneurysms developed at other sites.
      CONCLUSION: The surgical management of large, nonpulmonary arterial disease of
      Behcet disease is currently quite satisfactory. When the false aneurysm is in the
      infrarenal aorta, aorto-bi-iliac bypass is the preferred surgical intervention.
      Extremity aneurysms can be treated with synthetic graft insertion. In selected
      cases, ligation can give satisfactory results; however, postoperative
      claudication is common. In some patients with small intact saccular aneurysms,
      surgery may not be necessary. Patients must be prescribed immunosuppressive
      therapy with cyclophosphamide and corticosteroids before and after the surgical
      intervention in order to avoid Behcet disease activation.

PMID- 21944911
TI  - Prevention of neointimal hyperplasia associated with modified stretch expanded
      polytetrafluoroethylene hemodialysis grafts (Gore) in an experimental preclinical
      study in swine.
AB  - OBJECTIVE: Stenosis is the main cause of hemodialysis vascular graft failure and
      it is primarily caused by neointimal hyperplasia (NH) development at the vein
      graft anastomosis. Even though NH development factors are well known, their
      activation pathway still remains disputed and the real role of the mismatch
      compliance between the vein and the graft wall has not yet been resolved. The
      purpose of this experimental study in swine was to verify the possibility of
      preventing the development of NH at the vein-graft anastomosis using a modified
      commercially available longitudinal stretch expanded polytetrafluoroethylene
      (ePTFE) Gore (W. L. Gore & Associates, Flagstaff, Ariz) graft (either standard or
      heparin-bonded) with an added handmade ePTFE radial stretch cuff at one end to
      reduce the compliance between the graft and the vein wall. METHODS: Twelve ePTFE
      stretch grafts (6 modified and 6 unmodified) were surgically placed as
      arterovenous grafts (AVGs) between the carotid artery and the external jugular
      vein in 6 pigs. In each pig, one modified graft was placed on one side and one
      corresponding unmodified graft on the other side as a control. In 4 pigs,
      standard stretch ePTFE Gore grafts were used, and in 2 pigs, heparin-bonded
      stretch Gore grafts were used; 2 pigs were also treated with antiplatelet drugs.
      All the implanted grafts had a total length of 8 cm and a diameter of 6 mm. The
      modified graft was realized by cutting a short segment of the commercially
      available graft lengthwise which was then sewn crosswise (rotated 90 degrees )
      with the same diameter as the original graft and was then added to it. A Doppler
      ultrasound scan was used for monitoring the graft patency immediately, weekly,
      and before death. At death (21-28 days after implantation), artery, vein, and
      graft specimens were collected "en bloc" for histopathology. RESULTS: The
      modified grafts in the antiplatelet-treated animals were able to completely
      prevent NH development on vein wall (100% in 2 subjects) which was also reduced
      in antiplatelet untreated animals (66.5%, 96.4%, and 100% in 3 subjects,
      respectively). The modified standard stretch grafts and similarly modified
      heparin-bonded stretch grafts obtained the same good results in NH prevention.
      CONCLUSION: Data provide evidence of the efficacy of modified stretch ePTFE
      grafts with an added radial stretch cuff for the prevention of NH in swine models
      and support the hypothesis of the pivotal role of mismatch compliance between the
      graft and the vein wall in NH development.

PMID- 21944912
TI  - Compression therapy in mixed ulcers increases venous output and arterial
      perfusion.
AB  - OBJECTIVES: This study was conducted to define bandage pressures that are safe
      and effective in treating leg ulcers of mixed arterial-venous etiology. METHODS:
      In 25 patients with mixed-etiology leg ulcers who received inelastic bandages
      applied with pressures from 20 to 30, 31 to 40, and 41 to 50 mm Hg, the following
      measurements were performed before and after bandage application to ensure
      patient safety throughout the investigation: laser Doppler fluxmetry (LDF) close
      to the ulcer under the bandage and at the great toe, transcutaneous oxygen
      pressure (TcPo(2)) on the dorsum of the foot, and toe pressure. Ejection fraction
      (EF) of the venous pump was performed to assess efficacy on venous hemodynamics.
      RESULTS: LDF values under the bandages increased by 33% (95% confidence interval
      [CI], 17-48; P < .01), 28% (95% CI, 12-45; P < .05), and 10% (95% CI, -7 to 28),
      respectively, under the three pressure ranges applied. At toe level, a
      significant decrease in flux of -20% (95% CI, -48 to 9; P < .05) was seen when
      bandage pressure >41 mm Hg. Toe pressure values and TcPo(2) showed a moderate
      increase, excluding a restriction to arterial perfusion induced by the bandages.
      Inelastic bandages were highly efficient in improving venous pumping function,
      increasing the reduced ejection fraction by 72% (95% CI, 50%-95%; P < .001) under
      pressure of 21 to 30 mm Hg and by 103% (95% CI, 70%-128%; P < .001) at 31 to 40
      mm Hg. CONCLUSIONS: In patients with mixed ulceration, an ankle-brachial pressure
      index >0.5 and an absolute ankle pressure of >60 mm Hg, inelastic compression of
      up to 40 mm Hg does not impede arterial perfusion but may lead to a normalization
      of the highly reduced venous pumping function. Such bandages are therefore
      recommended in combination with walking exercises as the basic conservative
      management for patients with mixed leg ulcers.

PMID- 21944913
TI  - Nonoperative management of traumatic suprahepatic inferior vena cava
      pseudoaneurysms.
AB  - Inferior vena cava (IVC) pseudoaneurysms are rare clinical entities with an
      uncertain natural history due to limited follow-up information. This case report
      describes a 30-year-old woman with two IVC pseudoaneurysms and their associated
      anatomy. It also details our treatment plan, with follow-up through radiographic
      resolution of the pseudoaneurysms. To our knowledge, this is the first case
      report to document a patient with two pseudoaneurysms of the IVC and full
      resolution treated by nonoperative management.

PMID- 21944914
TI  - Surgical conversion for intragraft thrombosis following endovascular repair of
      traumatic aortic injury.
AB  - We report the case of a 32-year-old man with severe polytrauma, submitted to
      urgent endovascular exclusion of a posttraumatic thoracic aortic pseudoaneurysm.
      Two years later, computed tomography scan showed asymptomatic mural
      atherothrombosis of the aortic stent graft in its middle-distal portion, and the
      patient was placed on oral anticoagulants. As subsequent computed tomography scan
      showed progression of the thrombosis, the patient underwent surgical conversion,
      with stent graft explantation and in situ aortic replacement. Gross examination
      revealed mural organized thrombosis and a significant infolding of the distal end
      of the stent graft.

PMID- 21944915
TI  - Long-term outcomes after revascularization for advanced popliteal artery
      entrapment syndrome with segmental arterial occlusion.
AB  - OBJECTIVES: There are few long-term follow-up studies about the result of
      revascularization surgery for the treatment of popliteal artery entrapment
      syndrome (PAES). We performed this retrospective study to analyze the long-term
      result of revascularization surgery in patients with advanced PAES during the
      last 16 years. METHODS: Twenty-two limbs in 18 consecutive patients with PAES
      were treated surgically at Seoul National University Hospital between January
      1994 and December 2009. The preoperative diagnosis of PAES was made by duplex
      ultrasonography, three-dimensional computed tomography angiography, magnetic
      resonance imaging, or conventional angiography. The method of surgical approach
      was determined by the extent of arterial occlusion in preoperative images.
      RESULTS: The mean age was 31 years old and the majority of patients were men
      (94%). The chief complaints were claudication in 18 limbs, ischemic rest pain in
      three limbs, and toe necrosis in one limb. All 22 limbs underwent
      revascularization for advanced PAES with segmental arterial occlusion. Fourteen
      limbs underwent musculotendinous section and popliteo-popliteal interposition
      graft (13 posterior approaches, one medial approach), five femoropopliteal (below
      knee) bypasses, one femoro-posterior tibial bypass, and two popliteo-posterior
      tibial bypasses. All revascularization surgeries were performed with reversed
      saphenous veins. The overall primary graft patency rates at 1, 3, and 5 years
      were 80.9%, 74.6%, and 74.6%, respectively. Comparing 5-year graft patency
      according to the extent of arterial occlusion, patients with occlusion confined
      to the popliteal artery (n = 14) showed a better patency rate than patients with
      occlusion extended beyond the popliteal artery (n = 8) with no statistical
      significance (83.6% vs 53.6%; P = .053). Comparing 5-year graft patency according
      to the inflow artery, superficial femoral artery inflow (n = 6) showed a worse
      patency rate than popliteal artery inflow (n = 16) (30.0% vs 85.9%; P = .015).
      CONCLUSION: In advanced popliteal entrapment syndrome, longer bypass with
      superficial femoral artery inflow showed poor long-term graft patency rate. The
      graft patency rate was excellent in patients whose arterial occlusion was
      confined to the popliteal artery and treated by popliteal interposition graft
      with reversed saphenous vein. With these data, we suggest that longer bypass
      extending beyond the popliteal artery might only be indicated in patients with
      critical limb ischemia when the extent of disease does not allow short
      interposition graft.

PMID- 21944916
TI  - Circumferential heterogeneity in the abdominal aortic aneurysm wall composition
      suggests lateral sides to be more rupture prone.
AB  - OBJECTIVE: The purpose of this study was to identify local differences in
      inflammation and tissue degradation within the circumference of the abdominal
      aortic aneurysm (AAA). BACKGROUND: AAAs have the potential to rupture, and it is
      unknown why this predominantly occurs at the posterolateral wall. Blood flow
      dynamics likely influence rupture location but do not explain the whole picture,
      suggesting that other factors inside the AAA wall have a prominent role. METHODS:
      As part of the Aneurysm-Express study, full thickness circular biopsy specimens
      of AAAs from 25 patients were obtained during surgery according to a standardized
      protocol. Tissue from the dorsal, ventral, and lateral sides was processed for
      histology and protein extraction. Levels of matrix metalloproteinase (MMP)-2 and
      MMP-9 and various cytokines were measured. RESULTS: Lateral AAA sites, when
      compared with the ventral and dorsal segments, showed more microvessels (median
      [interquartile range] per mm(2), 91.8 [72.6-124.6] vs 73.9 [63.0-108.0] and 73.6
      [52.7-109.5]; P = .013 and P = .005, respectively) and more adventitial
      inflammation (16.1% [13.5%-24.7%] vs 5.8% [2.8%-18.6%] and 6.3% [4.3%-13.5%]; P =
      .001 and P < .001, respectively). We observed a higher active MMP-9 (0.139 [0.059
      0.339] ng/mL vs 0.060 [0.000-0.157] ng/mL and 0.045 [0.000-0.147] ng/mL; P = .001
      and P = .014, respectively) and higher interleukin-8 (28.644 [11.921-62.587]
      pg/mL vs 16.442 [4.300-34.130] pg/mL and 18.258 [8.273-44.989] pg/mL; P < .001
      and P = .010, respectively). CONCLUSION: Biopsy specimens of the ventral AAA wall
      do not optimally reflect the magnitude of inflammatory processes in the AAA. The
      lateral sides of the AAA contain more microvessels, more inflammatory cells, more
      active proteases, and higher cytokine levels. These results suggest that the
      lateral aortic regions are more rupture-prone and may better reflect the
      inflammatory status in histopathologic examinations.

PMID- 21944917
TI  - Gender-related outcomes in the endovascular treatment of infrainguinal arterial
      obstructive disease.
AB  - OBJECTIVE: The purpose of this study was to retrospectively analyze early and
      midterm results of endovascular infrainguinal peripheral revascularizations in
      female patients in our single-center experience, paying particular attention to
      clinical, anatomic, and technical factors affecting perioperative and follow-up
      outcomes. MATERIALS AND METHODS: From January 2000 to December 2010, 258
      endovascular interventions for femoropopliteal disease were performed.
      Interventions were retrospectively divided into two groups: interventions
      performed in women (80 interventions, group 1) and interventions performed in men
      (178 interventions, group 2). The two groups of patients were compared in terms
      of demographic data, common risk factors for atherosclerosis, and comorbidities.
      Early (intraoperative and <30-day) results were analyzed in terms of technical
      success, conversion to open surgery, primary patency, secondary patency, and, for
      patients with critical limb ischemia, limb salvage. The follow-up program
      consisted of clinical and duplex scanning examinations with ankle-brachial index
      (ABI) measurement within the third postoperative month, at 6 and 12 months, and
      yearly thereafter. Follow-up results were analyzed in terms of survival, primary
      and secondary patency, assisted primary patency, and, for patients with critical
      ischemia, limb salvage. RESULTS: There were no differences between the two groups
      in terms of risk factors for atherosclerosis, comorbidities, clinical, and
      anatomic status. Technical success was 96.9% and technical failure rates were
      1.2% in group 1 and 3.9% in group 2 (P = .2). Three in-hospital deaths were
      recorded, all in group 2, whereas in-hospital thromboses occurred in five
      patients, two in group 1 and three in group 2; with conversion to surgical bypass
      in all these cases, and in three of the cases, major amputation was necessary
      (two in group 1 and one in group 2). Cumulative 30-day mortality was 1.1%, with
      no difference between women (no deaths) and men (three deaths, 1.6%; P = .4).
      Overall amputation rate at 30 days was 1.2%, again with no differences between
      the two groups (2.5% and 0.6%, respectively; P = .4); also, the rate of
      perioperative thrombosis (overall 2.7%) was similar between the two groups (2.5%
      and 3.3%, respectively; P = .9). Mean duration of follow-up was 17 months (range,
      1-85 months). Estimated 36-month survival rates were 95% in group 1 and 84.5% in
      group 2 (P = .4; log-rank, 0.7). Cumulative primary patency rates at 36 months
      were 38% in group 1 and 42% in group 2 (P = .4; log-rank, 0.5). Assisted primary
      patency at 36 months was 45.1% in group 1 and 60.5% in group 2, whereas secondary
      patency rates were 63.5% and 76%, respectively (P = .8; log-rank, 0.03).
      CONCLUSION: Endovascular treatment of femoropopliteal occlusive disease provides
      similar results between men and women at an intermediate follow-up. There is,
      however, a trend toward poorer results in women requiring further analysis at a
      longer follow-up period.

PMID- 21944918
TI  - Impact of operative indication and surgical complexity on outcomes after thoracic
      endovascular aortic repair at National Surgical Quality Improvement Program
      Centers.
AB  - INTRODUCTION: Thoracic endovascular aortic repair (TEVAR) devices are
      increasingly being utilized to treat aortic pathologies outside of the original
      Food & Drug Administration (FDA) approval for nonruptured descending thoracic
      aorta aneurysms (DTAs). The objective of this study was to evaluate the outcomes
      of patients undergoing TEVAR, elucidating the role of surgical and pathologic
      variables on morbidity and mortality. METHODS: National Surgical Quality
      Improvement Program (NSQIP) data were reviewed for all patients undergoing
      endovascular thoracic aorta repair from 2005 to 2007. The patients' operative
      indication and surgical complexity were used to divide them into study and
      control populations. Comorbid profiles were assessed utilizing a modified
      Charlson Comorbidity Index (CCI). Thirty-day occurrences of mortality and serious
      adverse events (SAEs) were used as study endpoints. Univariate and multivariate
      models were created using demographic and clinical variables to assess for
      significant differences in endpoints (P <= .05). RESULTS: A total of 440 patients
      undergoing TEVAR were identified. When evaluating patients based on operative
      indication, the ruptured population had increased mortality and SAE rates
      compared to the nonruptured DTA population (22.6% vs 6.2%;P < .01 and 35.5% vs
      9.1%;P < .01, respectively). Further analysis by surgical complexity revealed
      increased mortality and SAE rates when comparing the brachiocephalic aortic
      debranching population to the noncovered left subclavian artery population (23.1%
      vs 6.5%; P = .02 and 30.8% vs 9.1%; P < .01, respectively). Multivariate analysis
      demonstrated that operative indication was not a correlate of mortality or SAEs
      (odds ratio [OR], 0.95; P = .92 and OR, 1.42; P = .39, respectively); however,
      brachiocephalic aortic debranching exhibited a deleterious effect on mortality
      (OR, 8.75; P < .01) and SAE rate (OR, 6.67; P = .01). CONCLUSION: The operative
      indication for a TEVAR procedure was not found to be a predictor of poor patient
      outcome. Surgical complexity, specifically the need for brachiocephalic aortic
      debranching and aortoiliac conduit, was shown to influence the occurrence of SAEs
      in a multivariate model. Comparative data, such as these, illustrate real-world
      outcomes of patients undergoing TEVAR outside of the original FDA-approved
      indications. This information is of paramount importance to various stakeholders,
      including third-party payers, the device industry, regulatory agencies, surgeons,
      and their patients.

PMID- 21944919
TI  - The durability of endovascular repair of para-anastomotic aneurysms after
      previous open aortic reconstruction.
AB  - INTRODUCTION: Anastomotic pseudoaneurysms and true para-anastomotic aneurysms
      after initial open abdominal aortic prosthetic reconstruction often need
      reintervention because they are at risk for rupture. However, open surgical
      reinterventions are technically challenging procedures with high mortality and
      morbidity rates. In the present multicenter study, we describe the long-term
      clinical course in an expanded number of patients who underwent endovascular
      repair of para-anastomotic aneurysms after previous open reconstruction. METHODS:
      The study included all patients who were treated with an endovascular stent graft
      between July 1999 and July 2009 for an aortoiliac anastomotic pseudoaneurysm or a
      true para-anastomotic aneurysm after previous aortic prosthetic reconstruction
      for aneurysmal or occlusive disease in one of the four participating centers.
      Main outcomes were long-term complications, reinterventions and conversion rate,
      mortality, and hospital length of stay. RESULTS: An endovascular stent graft was
      used to treat 58 patients (53 men; mean age, 71 +/- 9 years), with 80 aortic or
      iliac pseudoaneurysms or true para-anastomotic aneurysm, or both. Bifurcated
      stent grafts were used in 32 patients, endovascular tube grafts in eight,
      aortouniiliac stent grafts in seven, and iliac extension grafts in 11. Stent
      graft deployment was successful in 55 patients, for a technical success rate of
      95%. Median hospital admission was 3 days (range, 1-122 days). The 30-day and in
      hospital mortality rates were 3.4% (n = 2) and 6.9% (n = 4), respectively. The 30
      day clinical success rate was 91% (n = 53). Median follow-up was 41 months
      (range, 0-106 months). The cumulative and procedural-related mortality during
      follow-up was 19% (n = 11) and 10% (n = 6), respectively. Follow-up computed
      tomography angiography revealed nine endoleaks (three type I; six type II) in
      eight patients and endotension in two patients. The overall reintervention and
      conversion rate during follow-up was 26.9% (n = 15) and 6.9% (n = 4),
      respectively. Life-table analysis showed reduced freedom from reintervention for
      aortouniiliac and tube stent grafts. Type I endoleaks were observed in 25% of
      patients with endovascular aortic tube grafts for proximal anastomotic aneurysms.
      CONCLUSIONS: The present study demonstrates that endovascular repair of para
      anastomotic aortic and iliac aneurysms after initial prosthetic aortic surgery is
      safe and durable in patients with an appropriate anatomy. The long-term follow-up
      showed fewer complications occurred after procedures with bifurcated stent grafts
      compared with procedures with tube grafts, aortouniiliac, or iliac extension
      stent grafts.

PMID- 21944920
TI  - Pediatric venous thromboembolism in relation to adults.
AB  - OBJECTIVE: This review was performed to analyze the current knowledge and
      controversies in the pathophysiology, diagnosis, treatment, and outcomes of
      pediatric venous thromboembolism (VTE) compared with adults. METHODS: Searches of
      the MEDLINE database and manual searches of the references of selected articles
      were performed to select reports for their relevance and quality of information
      on the similarities and differences in pathophysiology, diagnosis, and treatment
      of VTE in children and adults. RESULTS: Symptomatic VTE incidence is reported at
      a rate of 0.07 in every 10,000 children, which is significantly lower than the
      rate in adults. Pulmonary emboli in adolescents are rarely fatal, unlike in
      adults. VTE recurrence is also much lower in children. Young age has been shown
      to be protective of VTE, whereas central venous catheters are very important in
      pediatric venous thrombosis. The incidence of postthrombotic syndrome varies from
      20% to 65%, with mild symptoms in most children. Cerebral and visceral vein
      thrombosis may lead to severe morbidity and death. Some factors of thrombophilia
      have a significant effect in the pediatric population; however, its overall
      significance is controversial. Most data on VTE treatment are extrapolated from
      studies in adults. Children with acute VTE should be treated with anticoagulation
      therapy. Treatment duration depends on the nature of the thrombosis and previous
      VTE events. CONCLUSIONS: There is a paucity of prospective randomized studies
      with data determining not only the effect of VTE but also the treatment options
      in children. Thrombophilia is a risk factor for pediatric VTE, but its
      significance has not been thoroughly investigated. Guidelines specific to
      children for antithrombotic therapy, prophylaxis, and optimal duration need re
      evaluation and support by strong evidence.

PMID- 21944921
TI  - The cardiovascular and prognostic significance of the infrarenal aortic diameter.
AB  - The normal aortic diameter in adults usually ranges from 16 to 18 mm in women and
      19 to 21 mm in men. Individuals with diameters outside this range seem to be at
      increased risk of other cardiovascular disease. There is a graded association
      between increasing aortic diameter and both cardiovascular mortality and
      peripheral arterial disease. The magnitude of increased risk of cardiovascular
      death seems to be about 4% to 6% per mm increase over a diameter of about 23 mm.
      To a lesser extent, these outcomes are also increased in individuals with aortic
      diameters below the normal range. While the threshold of 3 cm is useful in the
      diagnosis of abdominal aortic aneurysm (AAA), it is arbitrary in terms of the
      vascular biology and pathophysiology of the abdominal aorta. This review examines
      the risk factors for aortic enlargement and the cardiovascular implications of
      this enlargement in patients with and without AAAs. The mechanisms underlying the
      association between aortic diameter and cardiovascular risk and the relevance to
      screening are also discussed.

PMID- 21944922
TI  - New routing alternative for proximal anterior tibial artery bypass in patients
      with Buerger disease.
AB  - Femoral-anterior tibial artery bypasses with autogenous grafts are difficult to
      perform when sufficiently long saphenous veins are not available. We performed 12
      bypasses on patients with Buerger disease during a 20-year period using a new
      intermuscular tunneling technique. The graft is passed from the thigh between the
      muscle compartments without penetrating the muscle fibers, providing an
      anatomically superior and shorter path. The primary patency rates were 75% at 5
      years and 65% at 10 years. We believe that our tunneling technique is safe and
      durable and might be a viable alternative for proximal femoral-anterior tibial
      artery bypass in selected patients.

PMID- 21944923
TI  - Carbon nanotube-based ultrasensitive multiplexing electrochemical immunosensor
      for cancer biomarkers.
AB  - A multiplexing electrochemical immunosensor was developed for ultrasensitive
      detection of cancer related protein biomarkers. We employed disposable screen
      printed carbon electrode (SPCE) array as the detection platform. A universal
      multi-labeled nanoprobe was developed by loading HRP and goat-anti-rabbit IgG
      (secondary antibody, Ab(2)) onto multiwalled carbon nanotube (MWNT). This
      universal nanoprobe was available for virtually any sandwich-based antigen
      detection and showed superiority in several areas. By using the SPCE array and
      the universal nanoprobe, we could detect as low as 5 pg mL(-1) of prostate
      specific antigen (PSA) and 8 pg mL(-1) of Interleukin 8 (IL-8) with the
      electrochemical immunosensor. We also demonstrated simultaneous detection of two
      protein biomarkers with this platform. With these attracted features, our
      immunoassay system shows promising applications for in-field and point-of-care
      test in clinical diagnostics.

PMID- 21944924
TI  - Optical microchip array biosensor for multiplexed detection of bio-hazardous
      agents.
AB  - An optical waveguide array biosensor suitable for rapid detection of multiple bio
      hazardous agents is presented. SpectroSensTM optical microchip sensors contain
      multiple spatially-separated waveguide channels with integral high-precision
      Bragg gratings sensitive to changes in refractive-index; selective surface
      functionalisation of discrete sensing channels with different antibodies as bio
      recognition elements enables selective multi-analyte biological detection.
      Interactions between target antigens in the test sample and respective surface
      immobilised antibodies result in localised changes in refractive-index; the
      biosensor response manifests as increases in wavelength of light reflected from
      specific sensing channels. Multiplexed, label-free detection of 8 different
      biological agents, encompassing bacterial spores, vegetative cells, viruses and
      proteinaceous toxins has been demonstrated in real-time. Selective detection of
      Bacillus atrophaeus (BG) spores, Escherichia coli cells, MS2 viruses and
      ovalbumin (OVA) protein (simulant bio-hazardous agents) was first demonstrated as
      proof-of-concept; subsequently, detection of Bacillus anthracis (BA) spores
      (UM23CL2 strain), Franciscella tularensis (FT) cells (live vaccine strain),
      Vaccinia viruses (heat-killed) and ricin toxin (bio-hazardous agents) was proven.
      Two optical microchip sensors, each comprising 8 sensing channels were packaged
      into a single disposable cartridge allowing simultaneous 16-channel data
      acquisition. The specific antibody deposition sequence used in this study enabled
      detection of either 4 simulants or 4 bio-hazardous agents using a single
      consumable. The final device, a culmination of the multidisciplinary convergence
      of the fields of biology, chemistry, optoelectronics and microfluidics, is man
      portable and inherently robust. The performance characteristics of the
      SpectroSensTM technology platform highlight its potential for exploitation as a
      'detect to warn/treat' biodetector in security and defence operations.

PMID- 21944925
TI  - GL-V9, a newly synthetic flavonoid derivative, induces mitochondrial-mediated
      apoptosis and G2/M cell cycle arrest in human hepatocellular carcinoma HepG2
      cells.
AB  - We recently established that GL-V9, a newly synthetic flavonoid derivative, is an
      active cytotoxic component. In this study, we demonstrated that GL-V9 inhibited
      cells growth via inducing apoptosis and G2/M cell cycle arrest in human
      hepatocellular carcinoma HepG2 cells. Following the treatment of HepG2 cells with
      GL-V9, we observed poly (ADP-ribose) polymerase (PARP) cleavage and activation of
      caspase-3 and caspase-9, while caspase-8 remained unchanged. The expression ratio
      of Bcl-2/Bax was also decreased in GL-V9-treated cells. Meanwhile, the cell cycle
      related proteins, such as cyclin B1, CDK1 and cdc25 were down-regulated in GL-V9
      induced G2/M cell cycle arrest. Furthermore, we showed that GL-V9-induced
      apoptosis in HepG2 cells was achieved through mitochondrial pathway. It also
      regulated changes of mitochondrial membrane potential and increased the
      production of intracellular reactive oxygen species. Besides, the growth
      inhibitory effect of GL-V9 was examined in vivo using murine implanted tumor
      model. These studies indicate that GL-V9 shows promise as a therapeutic agent
      against human hepatoma.

PMID- 21944927
TI  - Perioperative results following open and minimally invasive single-level lumbar
      discectomy.
AB  - Lumbar discectomy is the most commonly performed spine surgery and in recent
      years, minimally invasive tubular discectomy has become increasingly popular
      among surgeons and patients. However, recent reports have raised the question of
      whether or not patients have shorter hospitalizations following minimally
      invasive discectomy. From 2005 to 2010, we analyzed 109 patients who underwent
      elective, single-level lumbar discectomy for central or paracentral disc
      herniations. A retrospective analysis of medical records was performed for
      perioperative complications. Tubular discectomy was not associated with increased
      rates of durotomy, nerve root injury, wound complications, or recurrent disc
      herniations requiring additional surgery. Minimally invasive tubular discectomy
      in the lumbar spine results in a small, but statistically significant, advantage
      in length of stay compared to conventional open microdiscectomy. While small on
      an individual basis, this difference may translate to substantial economic
      savings over time when one considers how many discectomies are performed in
      aggregate.

PMID- 21944926
TI  - The novel small molecule alpha9alpha10 nicotinic acetylcholine receptor
      antagonist ZZ-204G is analgesic.
AB  - Chronic pain is inadequately managed with currently available classes of
      analgesic drugs. Recently, peptide antagonists of the alpha9alpha10 nicotinic
      acetylcholine receptor were shown to be analgesic. The present study was
      conducted to characterize a novel small molecule, non-peptide antagonist at
      nicotinic receptors. The tetrakis-quaternary ammonium compound ZZ-204G was
      evaluated for functional activity on cloned nicotinic receptors expressed in
      Xenopus oocytes. In-vivo efficacy was assessed in rat models of tonic
      inflammatory pain (formalin test), neuropathic pain (chronic constriction nerve
      injury), and thermal nociception (tail flick test). ZZ-204G was an antagonist at
      nicotinic receptors inhibiting the alpha9alpha10 subtype with an IC50 of 0.51
      (0.35-0.72) nM. Antagonist activity at other nicotinic subtypes
      (alpha1beta1deltaepsilon, alpha2beta2, alpha2beta4, alpha3beta2, alpha3beta4,
      alpha4beta2, alpha4beta4, alpha6/alpha3beta2beta3, alpha6/alpha3beta4 and alpha7)
      was 10-1000-fold lower than at the alpha9alpha10 subtype. In competition binding
      assays, the k(i) of ZZ-204G at gamma-aminobutyric acid(A), serotonin(3), gamma
      aminobutyric acid(B), kappa- and MU-opioid receptors was 1000- to >10,000-fold
      lower than at alpha9alpha10 nicotinic receptors. Parenteral administration of ZZ
      204G dose-dependently decreased nociceptive behaviors (paw flinches) in the
      formalin test and mechanical hyperalgesia in the chronic constriction nerve
      injury model of neuropathic pain. ZZ-204G was not antinociceptive in the tail
      flick assay. Results from the rotarod assay indicated that lower doses of ZZ-204G
      that were analgesic did not alter motor function. In summary, ZZ-204G represents
      a prototype small molecule antagonist for alpha9alpha10 nicotinic receptors and
      provides a novel molecular scaffold for analgesic agents with the potential to
      treat chronic inflammatory or neuropathic pain.

PMID- 21944929
TI  - Number of CGG repeats in the FMR1 gene of Japanese patients with primary ovarian
      insufficiency.
AB  - OBJECTIVE: To define the number of CGG repeats in the FMR1 gene of Japanese
      patients with primary ovarian insufficiency (POI) and normal controls. DESIGN:
      Retrospective, controlled cohort study. SETTING: Outpatient department of an
      academic tertiary center. PATIENT(S): One hundred twenty-eight consecutive
      Japanese patients with sporadic, nonsyndromic POI and 98 controls with normal
      menstruation. INTERVENTION(S): Deoxyribonucleic acid was obtained from the plasma
      of each subject. MAIN OUTCOME MEASURE(S): Differences in the distribution of CGG
      repeat numbers between patients with POI and controls. RESULT(S): Six alleles in
      the intermediate range and two in the premutation range were found in five and
      two patients with POI, respectively, but none were identified in normal controls.
      The prevalence of FMR1 premutation among Japanese POI patients was 1.56% (2 of
      128). The prevalence of having >36 CGG repeats in the FMR1 gene was significantly
      higher in patients with POI than in controls, and age at the onset of amenorrhea
      was significantly lower in patients with >38 repeats. CONCLUSION(S): More than 36
      CGG repeats in the FMR1 might intensify the etiology of POI, at least up to the
      premutation range.

PMID- 21944930
TI  - Virtual hysterosalpingography in the diagnosis of bicornuate versus septate
      uterus.
AB  - OBJECTIVE: To study the value of virtual hysterosalpingography (VHSG) in the
      diagnosis of bicornuate vs. septate uterus. DESIGN: Retrospective study of all
      cases with bicornuate or septate uterus that had VHSG during the last 3 years at
      our center. SETTING: Private fertility center and radiology institute with
      university affiliations. PATIENT(S): A total of 47 patients (from more than 1,000
      studies) with bicornuate uterus (n = 15) or septate uterus (n = 32) were analyzed
      to determine the ability of VHSG to distinguish both entities. INTERVENTION(S):
      Virtual hysterosalpingography was performed in patients with bicornuate or
      septate uterus. MAIN OUTCOME MEASURE(S): Procedure length, discomfort, amount of
      radiation, and ability to outline the uterine fundus. RESULT(S): We were able to
      clearly distinguish bicornuate from septate uterus. In all patients who underwent
      septoplasty the VHSG diagnosis of septate uterus was confirmed. Virtual
      hysterosalpingography was well tolerated by all patients; scanning took 5 seconds
      per patient, and the average radiation was very low (0.9 +/- 0.7 mSv).
      CONCLUSION(S): Virtual hysterosalpingography seems to be a valuable tool in the
      diagnosis of common uterine anomalies.

PMID- 21944928
TI  - Smaller fetal size in singletons after infertility therapies: the influence of
      technology and the underlying infertility.
AB  - OBJECTIVE: To determine whether fetal size differences exist between matched
      fertile and infertile women and among women with infertility achieving pregnancy
      through various treatment modalities. DESIGN: Retrospective cohort study with
      propensity score analysis. SETTING: Tertiary care center and affiliated community
      hospitals. PATIENT(S): 1,246 fertile and 461 infertile healthy women with
      singleton livebirths over a 10-year period. INTERVENTION(S): Infertile women
      conceiving without medical assistance, with ovulation induction, or with in vitro
      fertilization. MAIN OUTCOME MEASURE(S): Birthweight; secondary outcomes included
      crown-rump length, second-trimester estimated fetal weight, and incidence of low
      birth weight and preterm delivery. RESULT(S): Compared with matched fertile
      women, infertile women had smaller neonates at birth (3,375 +/- 21 vs. 3,231 +/-
      21 g) and more low-birth-weight infants (relative risk = 1.68, 95% confidence
      interval, 1.06, 2.67). Neonates conceived via ovulation induction were the
      smallest among the infertility subgroups compared with the neonates of fertile
      women (3,092 +/- 46 vs. 3,397 +/- 44 g). First-trimester fetal size was smaller
      in infertile versus fertile women (crown-rump length 7.9 +/- 0.1 vs. 8.5 +/- 0.1
      mm). Within the infertility subgroups, no differences in fetal or neonatal size
      were found. CONCLUSION(S): The inherent pathologic processes associated with
      infertility may have a larger impact on fetal growth than infertility therapies.

PMID- 21944931
TI  - [Incidence and factors related to excessive intrapartum blood loss].
AB  - INTRODUCTION: Childbirth and postpartum carry a high potential risk to the woman,
      with bleeding being a major cause of morbidity and mortality. A drop in
      haemoglobin >= 3.5 g during the delivery process is considered as excessive
      bleeding, and is used as an indicator of quality of care in childbirth.
      OBJECTIVE: To determine the incidence and factors associated with excessive
      intrapartum blood loss. SUBJECTS AND METHODS: Hybrid design nested case-control
      study was performed in a cohort of 1488 pregnant women who gave birth at the
      Hospital La Mancha-Centro in 2008. We selected all the cases (84 subjects with a
      haemoglobin loss of >= 3.5 g) and twice the number of controls (164) matched by
      time of delivery. Multivariate analysis was performed using conditional logistic
      regression. RESULTS: The incidence of excessive intrapartum bleeding was 6.6%,
      with no significant differences regarding the mode of delivery (Vaginal and
      Caesarean=6.8%=5.6%). Antepartum anaemia was around 10% and postpartum anaemia
      41.4%. We found no factors associated with bleeding in Caesarean deliveries.
      However, in the vaginal primiparity, manual removal and particularly the practice
      of episiotomy [OR=4.82 (95% CI, 1.73 to 13.44] are presented as clear risk
      factors. CONCLUSION: The incidence of excessive bleeding is above recommended
      levels. Primiparity, manual removal and particularly episiotomy are risk factors
      for bleeding.

PMID- 21944932
TI  - [The hospital transfer of a patient with gastrointestinal bleeding from
      oesophageal varices].
AB  - The care of patients with gastrointestinal bleeding from oesophageal varices
      during inter-hospital transfer is a complex procedure to different causes. Some
      of these include, the high number of parameters to take into account, the
      monitoring of the electro-medical equipment, the instability of the patient and
      their needs or the short time available to know the patient and obtain the
      maximum information in order to plan a safe and proper transfer. The main role of
      the nurse in the transfer of critically ill patients focuses on the control and
      monitoring of all these aspects and the maintenance of the continuity of the
      caring initiated in the hospital. This requires a personalized care plan to be
      prepared for the patient who has to be transferred to avoid putting the
      individual at risk due to their high vulnerability. This should minimise the risk
      of possible complications or accidental incidents related to the high number of
      instruments used for monitoring the patients during their transfer. The case
      presented below describes the transfer of a patient by ambulance from a level 2
      hospital to a level 3 hospital of a person who had an urgent condition that
      reflected all this complexity. It highlights the indications and basic care that
      has to be taken into account in this type of transfer and the transfer of the
      patient once in the receiving hospital, especially in this case, where the
      condition of the patient is highly compromised.

PMID- 21944933
TI  - Stem cells in burn eschar.
AB  - This study compares mesenchymal cells isolated from excised burn wound eschar
      with adipose-derived stem cells (ASCs) and dermal fibroblasts in their ability to
      conform to the requirements for multipotent mesenchymal stem cells (MSCs). A
      population of multipotent stem cells in burn eschar  could be an interesting
      resource for tissue engineering approaches to heal burn wounds. Cells from burn
      eschar, dermis, and adipose tissue were assessed for relevant CD marker profiles
      using flow cytometry and for their trilineage differentiation ability in
      adipogenic, osteogenic, and chondrogenic  conditions. Although the different cell
      types did not differ significantly in their CD marker expression, the eschar
      derived cells and ASCs readily differentiated into adipocytes, osteoblasts, and
      chondrocytes, while dermal fibroblasts only exhibited some chondrogenic
      potential. We conclude  that the eschar-derived mesenchymal cells represent a
      population of multipotent stem cells. The origin of the cells from burn eschar
      remains unclear, but it is likely they represent a population of adult stem cells
      mobilized from other parts of the body in response to the burn injury. Their 
      resemblance to ASCs could also be cause for speculation that in deep burns the
      subcutaneous adipose tissue might be an important stem cell source for the
      healing wound.

PMID- 21944934
TI  - Sonochemical shape control of copper hydroxysulfates.
AB  - Shape control of inorganic nanoparticles generally requires the use of
      surfactants or ligands to passivate certain crystallographic planes. Additive
      free shape control methods utilize the differences in the growth rates of
      crystallographic planes. We combined this approach with the sonochemical method
      to synthesize copper hydroxysulfate (Brochantite) with morphologies ranging from
      flowers, to bricks, belts and needles. Sodium peroxydisulfate, which was used as
      the sulfate and hydroxide source, was decomposed thermally and/or sonically under
      various pH and temperature conditions. The relative release rates of the sulfate
      and hydroxide anions determined the final form of the crystals. This technique
      yielded products even at acidic pH, marking a distinction from the literature
      reactions, which start with stoichiometric amounts of sulfate and hydroxide
      anions and yield only a single crystal morphology.

PMID- 21944935
TI  - Surveillance of transfusion-transmissible infections comparison of systems in
      five developed countries.
AB  - Most industrialized countries maintain surveillance programs for monitoring
      transmissible infection in blood donations, revising approaches to methodology
      and risk assessment as new threats emerge. A comparison of programs in the United
      States, Canada, France, the UK, and Australia indicates that they have similar
      function, although the structure of blood programs vary as does the extent and
      nature of formal ties with public health. The emergence of HIV in the late 1970s
      and early 1980s was key in recognizing that surveillance systems specific to
      blood transfusion were essential. Hence, most industrialized countries monitor
      transfusion-transmissible infections in donors and evaluate the impact of new
      testing and of predonation screening strategies. Emerging infections since HIV
      have had different transmission pathways and challenged blood programs to draw
      upon resources for a rapid and effective response, with recognition that the
      original focus on sexual/drug-related risk of HIV and hepatitis was inadequate.
      The focus of surveillance programs on new and emerging pathogens fulfills a key
      role in risk assessment and policy formulation. The precise nature of such
      activities varies by country because of the structure of the blood programs and
      surveillance systems, the strategic focus of the blood programs, and the
      epidemiology of disease in each country.

PMID- 21944936
TI  - PCR amplification of repetitive sequences as a possible approach in relative
      species quantification.
AB  - Both relative and absolute quantifications are possible in species quantification
      when single copy genomic DNA is used. However, amplification of single copy
      genomic DNA does not allow a limit of detection as low as one obtained from
      amplification of repetitive sequences. Amplification of repetitive sequences is
      therefore frequently used in absolute quantification but problems occur in
      relative quantification as the number of repetitive sequences is unknown. A
      promising approach was developed where data from amplification of repetitive
      sequences were used in relative quantification of species in binary mixtures. PCR
      LUX primers were designed that amplify repetitive and single copy sequences to
      establish the species dependent number (constants) (SDC) of amplified repetitive
      sequences per genome. The SDCs and data from amplification of repetitive
      sequences were tested for their applicability to relatively quantify the amount
      of chicken DNA in a binary mixture of chicken DNA and pig DNA. However, the
      designed PCR primers lack the specificity required for regulatory species
      control.

PMID- 21944937
TI  - UK population data generated with the PowerPlex(r) ESI 16 system.

PMID- 21944938
TI  - B-lymphocyte commitment: identifying the point of no return.
AB  - Even though B-lymphocyte development is one of the best understood models for
      cell differentiation in the hematopoetic system, recent advances in cell sorting
      and functional genomics has increased this understanding further. This has
      suggested that already early lymphoid primed multipotent progenitor cells (LMPPs)
      express low levels of lymphoid restricted transcripts. The expression of these
      genes becomes more pronounced when cells enter the FLT-3/IL-7 receptor positive
      common lymphoid progenitor (CLP) stage. However, the expression of B-lineage
      specific genes is limited to a B-cell restricted Ly6D surface positive
      subpopulation of the CLP compartment. The gene expression patterns also reflect
      differences in lineage potential and while Ly6D negative FLT-3/IL-7 receptor
      positive cells represents true CLPs with an ability to generate B/T and NK cells,
      the Ly6D positive cells lack NK cell potential and display a reduced T-cell
      potential in vivo. These recent findings suggest that the CLP compartment is
      highly heterogenous and that the point of no return in B-cell development may
      occur already in B220(-)CD19(-) cells. These findings have allowed for a better
      understanding of the interplay between transcription factors like EBF-1, PAX-5
      and E47, all known as crucial for normal B-cell development. In this review, we
      aim to provide a comprehensive overview of B-cell fate specification and
      commitment based on the recent advances in the understanding of molecular
      networks as well as functional properties of early progenitor populations.

PMID- 21944939
TI  - Task-dependent effects of interhemispheric inhibition on motor control.
AB  - Interhemispheric communication consists of a complex balance of facilitation and
      inhibition that is modulated in a task-dependent manner. However, it remains
      unclear how individual differences in interhemispheric interactions relate to
      motor performance. To assess interhemispheric inhibition, we utilized the
      ipsilateral silent period technique (iSP; evoked by suprathreshold transcranial
      magnetic stimulation), which elicits inhibition of volitional motor activity.
      Participants performed three force production tasks: (1) unimanual (right hand)
      constant force, (2) bimanual constant force, (bimanual simultaneous) and (3)
      bimanual with right hand constant force and left hand sine wave tracking
      (bimanual independent). We found that individuals with greater IHI capacity
      demonstrated reduced mirror EMG activity in the left hand during unimanual right
      hand contraction. However, these same individuals demonstrated the poorest
      performance during the bimanual independent force production task. We suggest
      that a high capacity for IHI from one motor cortex to another can effectively
      prevent "motor overflow" during unimanual tasks, but it can also limit
      interhemispheric cooperation during independently controlled bimanual tasks.

PMID- 21944940
TI  - The neuroprotective effect of vitamin E on chronic sleep deprivation-induced
      memory impairment: the role of oxidative stress.
AB  - Sleep deprivation induces oxidative stress and impairs learning and memory
      processes. Vitamin E, on the other hand, is a strong antioxidant that has
      neuroprotective effect on the brain. In this study, we examined the potential
      protective effect of chronic administration of vitamin E on chronic sleep
      deprivation-induced cognitive impairment. In addition, possible molecular targets
      for vitamin E effects on chronic sleep deprivation-induced cognitive impairment
      were determined. Sleep deprivation was induced in rats using modified multiple
      platform model. Vitamin E (100mg/kg) was administered to animals by oral gavage.
      Behavioral study was conducted to test the spatial learning and memory using the
      radial arm water maze (RAWM). In addition, the hippocampus was dissected out and
      antioxidant markers including glutathione (GSH), oxidized glutathione (GSSG) and
      GSH/GSSG, glutathione peroxidase (GPx), catalase, and superoxide dismutase (SOD)
      were assessed. The results of this project revealed that chronic sleep
      deprivation impaired both (short- and long-term) memories (P<0.05), while vitamin
      E treatment prevented such effect. Additionally, vitamin E normalized chronic
      sleep deprivation-induced reduction in the hippocampus GSH/GSSG ratio, and
      activity of catalase, SOD, and GPx. In conclusion, sleep deprivation induces
      memory impairment, and treatment with vitamin E prevented this impairment
      probably through its antioxidant action in the hippocampus.

PMID- 21944941
TI  - Cognition in female transmembrane domain neuregulin 1 mutant mice.
AB  - Neuregulin 1 (Nrg1) has been implicated in the development of schizophrenia and
      influences key neurodevelopmental processes such as myelination and neuronal
      migration. The heterozygous transmembrane domain Nrg1 mutant mouse (Nrg1 TM HET)
      exhibits a sex-specific phenotype relevant for schizophrenia research, which is
      characterized by the development of locomotor hyperactivity, social withdrawal,
      and changes to the serotonergic system. Cognitive impairments are characteristic
      of schizophrenia patients and male Nrg1 TM HET mice exhibit cognitive deficits in
      novel object recognition and contextual fear conditioning. Thus, we investigated
      the cognitive performance of female Nrg1 mutants, using a cognitive test battery
      for a variety of paradigms, including fear conditioning, cheeseboard, Y maze,
      object exploration and passive avoidance. Female Nrg1 mutant mice displayed
      impairments in the fear conditioning tasks, including significantly reduced fear
      conditioning to a context and a strong trend towards a decreased ability for cue
      fear conditioning. These cognitive deficits were task-specific, as no differences
      were seen between mutant and control mice in spatial learning of the cheeseboard
      for reference memory measures, in the Y-maze for working memory measures, or in
      novel object recognition and passive avoidance paradigms. These findings indicate
      that neuregulin 1 plays only a minor role in cognition in female test mice. The
      current study provides a further behavioural validation of this genetic mouse
      model for the schizophrenia candidate gene neuregulin 1 and confirms the
      importance of considering female test animals in animal models for schizophrenia.

PMID- 21944942
TI  - Serological characterizations of tandem repeat proteins for detection of African
      trypanosome infection in cattle.
AB  - Serological diagnosis is a useful method to detect African trypanosome infection
      in livestock animals. Currently available serological tests utilize whole
      parasites or crude antigens, and recombinant antigens may improve
      reproducibility/standardization and reduce production costs. With a goal of
      identifying such recombinant proteins, we computationally identified proteins
      with tandem repeat (TR) domain from the parasite proteomes and evaluated their
      potential for serological diagnosis of African trypanosome infections in cattle.
      Among those tested, Tbg4 demonstrated the best performance with 92% sensitivity,
      followed by TbbGM6 (85%), TcoGM6 (85%), Tbg2 (65%) and Tbg5 (65%). Although
      further evaluations such as investigating cross-reactivity to other infections
      are needed, our data indicate the potential of these antigens for detection of
      African trypanosome infection in cattle.

PMID- 21944943
TI  - Monoclonal antibodies for the treatment of asthma.
AB  - Asthma is a chronic inflammatory disease of the airways which can have a
      detrimental effect on quality of life and in extreme cases cause death. Although
      the majority of patients can control their asthma symptoms with a combination of
      steroids and beta agonists there is still a group of patients whose asthma
      remains symptomatic despite the best available treatment. These severe asthmatic
      patients represent the unmet medical need in asthma and are the focus of those
      developing novel monoclonal antibody based drugs. The complex networks of
      cytokines and cells involved in the pathology of asthma provide plenty of scope
      for intervention with monoclonal antibody based drugs which are able to block
      cytokine or chemokine receptor interactions, deplete cells expressing a specific
      receptor or block cell/cell interactions. At present anti-IgE (Xolair(c)) is the
      only monoclonal antibody based drug approved for the treatment of asthma.
      However, a number of other antibody based drugs have been clinically tested in
      asthma including anti-IL-5, anti-IL-4, anti-IL-13, anti-TNFalpha, anti-CCR3, anti
      CCR4 and anti-OX40L. This review will examine the development of these monoclonal
      antibody based therapies. Since many of these therapies have targeted key
      pathways in asthma pathology these studies provide information on patient
      stratification and asthma pathology.

PMID- 21944944
TI  - On the differential diagnosis of Meniere's disease using low-frequency acoustic
      biasing of the 2f1-f2 DPOAE.
AB  - We have cyclically suppressed the 2f1-f2 distortion product otoacoustic emission
      (DPOAE) with low-frequency tones (17-97 Hz) as a way of differentially diagnosing
      the endolymphatic hydrops assumed to be associated with Meniere's syndrome. Round
      window electrocochleography (ECochG) was performed in subjects with sensorineural
      hearing loss (SNHL) on the day of DPOAE testing, and from which the amplitude of
      the summating potential (SP) was measured, to support the diagnosis of Meniere's
      syndrome based on symptoms. To summarize and compare the cyclic patterns of DPOAE
      modulation in these groups we have used the simplest model of DPOAE generation
      and modulation, by assuming that the DPOAEs were generated by a 1st-order
      Boltzmann nonlinearity so that the magnitude of the 2f1-f2 DPOAE resembled the
      3rd derivative of the Boltzmann function. We have also assumed that the
      modulation of the DPOAEs by the low-frequency tones was simply due to a
      sinusoidal change in the operating point on the Boltzmann nonlinearity. We have
      found the cyclic DPOAE modulation to be different in subjects with Meniere's
      syndrome (n = 16) when compared to the patterns in normal subjects (n = 16) and
      in other control subjects with non-Meniere's SNHL and/or vestibular disorders (n
      = 13). The DPOAEs of normal and non-Meniere's ears were suppressed more during
      negative ear canal pressure than during positive ear canal pressure. By contrast,
      DPOAE modulation in Meniere's ears with abnormal ECochG was greatest during
      positive ear canal pressures. This test may provide a tool for diagnosing
      Meniere's in the early stages, and might be used to investigate the pathological
      mechanism underlying the hearing symptoms of this syndrome.

PMID- 21944945
TI  - The effect of calf muscle stretching exercises on ankle joint dorsiflexion and
      dynamic foot pressures, force and related temporal parameters.
AB  - BACKGROUND: Previous research has found that ankle joint equinus can lead to foot
      pathologies. Calf stretching exercises are a common treatment prescription;
      however, no dynamic quantitative data on its effectiveness is available.
      OBJECTIVE: To investigate the effect of calf muscle stretching on ankle joint
      dorsiflexion and subsequent changes within dynamic forefoot peak plantar
      pressures (PPP), force and temporal parameters. METHOD: Thirteen runners with
      ankle joint equinus were required to perform calf muscle stretching twice a day
      (morning and evening) on a Flexeramp. Measurements were collected on day 1, week
      4 and week 8. A repeated measures ANOVA with Bonferroni-adjusted post hoc
      comparisons was used to assess differences across the three data collection
      sessions. RESULTS: Findings indicated that the calf stretching program increased
      ankle joint dorsiflexion significantly (from 5 degrees  to 16 degrees , p<=0.05).
      The adaptive kinetics brought about by the increased ankle joint range of motion
      included significantly increased forefoot PPP and maximum force during stance
      phase but decreased time between heel contact and heel lift and total stance
      phase time. CONCLUSION: The calf stretching programme used in this study was
      found to increase ankle joint dorsiflexion and hence can be used for first line
      conservative management of ankle equinus.

PMID- 21944946
TI  - Electrocommunication behaviour and non invasively-measured androgen changes
      following induced seasonal breeding in the weakly electric fish, Apteronotus
      leptorhynchus.
AB  - Androgens are known to be involved in reproductive behaviours including courtship
      and aggression. According to the Challenge Hypothesis, androgen activity
      upregulates male reproductive behaviour seasonally and also modulates short term
      adaptation of these behaviours in response to social context. In the weakly
      electric fish, Apteronotus leptorhynchus, 11-ketotestosterone (11-KT) has been
      previously implicated in the regulation of electrocommunication behaviours that
      are believed to have roles in both aggression and courtship. Changes in male 11
      KT levels were quantified using a non-invasive measurement technique alongside
      changes in electrocommunication behaviour following environmental cues that
      simulated the onset of the breeding season. Males showed an increase in mean
      electric organ discharge frequency (EODf), which is consistent with earlier
      results showing a female preference for high EODf. A subset of males with high
      initial EODfs showed increases in both 11-KT and EODf, which provides support for
      an EODf-based dominance hierarchy in this species. Males housed in social
      conditions and exposed to breeding conditioning also showed higher overall
      electric organ discharge frequencies and 11-KT compared to males housed in
      isolation. Evidence is presented that another type of electrocommunication signal
      previously implicated in courtship may also serve as an inter-male signal of
      submission. Our results are consistent with earlier observations that
      electrocommunication signals produced during inter-male aggression serve in
      deterring attacks, and their pattern of production further suggested the
      formation of a dominance hierarchy.

PMID- 21944947
TI  - Triple combinations of neuraminidase inhibitors, statins and fibrates benefit the
      survival of patients with lethal avian influenza pandemic.
AB  - The high mortality of highly pathogenic avian influenza A (H5N1) viruses
      infection in humans gives rise to considerable concern that it might someday
      cause another lethal pandemic. At present there is no other effective alternative
      besides the early and enough administration of neuraminidase inhibitors, which
      may be crucial for the patient management. However, its efficacy is sometimes
      limited because of the late administration in some patients especially the
      seriously ill ones and the continual occurrence of oseltamivir resistant A (H5N1)
      strains. The specific candidate vaccine are still under development and the
      practical value of passive immunization is hard to be widely applied because of
      the scarcity of convalescent human plasma, especially in the early stage of a
      serious and rapidly progressing pandemic. Statins and fibrates, both of which are
      used in clinical practice, have anti-inflammatory and immunomodulatory effects
      and other multiple biologic activities. So we hypothesized that the two
      immunomodulatory agents may exhibit synergistic effects when they were combined
      to neuraminidase inhibitors to treat the A (H5N1) viruses infections via
      inhibiting the production of either the early inflammatory mediators (e.g., many
      cytokine/chemokine) or the late mediator (e.g., High Mobility Group Box Protein
      1), even showing the anti-viral activities with the prevention of the development
      of antiviral resistance. Therefore, the novel triple combinations may be an
      optimal management to confront the next lethal influenza pandemic on its very
      beginning.

PMID- 21944948
TI  - Tuberculous peritonitis: analysis of 211 cases in Taiwan.
AB  - BACKGROUND: Tuberculosis infection caused by Mycobacterium tuberculosis or other
      Mycobacterium species is a major communicable disease worldwide. AIM: We
      evaluated the epidemiology of tuberculous peritonitis to determine diagnostic
      features and factors related to late diagnosis. METHODS: We retrospectively
      reviewed 211 tuberculous peritonitis cases diagnosed between January 1999 and
      December 2009. Clinical features, laboratory data, and diagnostic methods were
      analysed. RESULTS: Subjects included 115 males (54.5%) and 96 females (45.5%)
      with median age 61.0 years (range 43-72) and 29.2 days mean duration from
      symptoms to diagnosis. Disease histories included end-stage renal disease
      (20.9%), pulmonary tuberculosis (36.0%) and liver cirrhosis (23.7%). Most common
      symptoms were abdominal distension (80.1%), abdominal pain (68.7%) and weight
      loss (45.5%). Most common signs were ascites (62.6%) and fever (55.5%). One-year
      survival rate was 89.9%; 21 patients died during follow-up. Mortality risk was
      higher in patients with more concomitant diseases, including liver cirrhosis,
      AIDS, chronic steroid use, alcoholism, GI bleeding, haemoptysis, period from
      symptom presentation to treatment, secondary bacterial peritonitis requiring
      emergent operation. CONCLUSIONS: Increased duration between symptoms and
      definitive diagnosis increases mortality risk. Early diagnosis and prompt
      initiation of anti-tuberculosis therapy improve prognosis. Neutrophil-predominant
      ascites influences poor prognosis when correlated with secondary bacterial
      peritonitis.

PMID- 21944949
TI  - Is it possible to improve the histological yield of oesophageal endoscopic
      mucosectomies?

PMID- 21944950
TI  - Endoscopic ultrasound image of alpha-fetoprotein-producing pancreatic acinar cell
      carcinoma.

PMID- 21944952
TI  - Laparoscopic sleeve gastrectomy is a misnomer.

PMID- 21944951
TI  - Pre- to postoperative changes in physical activity: report from the longitudinal
      assessment of bariatric surgery-2 (LABS-2).
AB  - BACKGROUND: Numerous studies have reported that bariatric surgery patients report
      more physical activity (PA) after surgery than before; however, the quality of
      the PA assessment has been questionable. METHODS: The longitudinal assessment of
      bariatric surgery-2 is a 10-center longitudinal study of adults undergoing
      bariatric surgery. Of 2458 participants, 455 were given an activity monitor,
      which records the steps per minute, and an exercise diary before and 1 year after
      surgery. The mean number of steps/d, active min/d, and high-cadence min/wk were
      calculated for 310 participants who wore the monitor >=10 hr/d for >=3 days at
      both evaluations. Pre- and postoperative PA were compared for differences using
      the Wilcoxon signed-rank test. Generalized estimating equations were used to
      identify independent preoperative predictors of postoperative PA. RESULTS: PA
      increased significantly (P < .0001) from before to after surgery for all PA
      measures. The median values before and after surgery were 7563 and 8788 steps/d,
      309 and 340 active min/d, and 72 and 112 high-cadence min/wk, respectively.
      However, depending on the PA measure, 24-29% of participants were >=5% less
      active postoperatively than preoperatively. Controlling for surgical procedure,
      gender, age, and body mass index, more PA preoperatively independently predicted
      for more PA postoperatively (P < .0001, for all PA measures). Less pain, not
      having asthma, and the self-report of increasing PA as a weight loss strategy
      preoperatively also independently predicted for more high-cadence min/wk
      postoperatively (P < .05). CONCLUSIONS: The majority of adults increase their PA
      level after bariatric surgery. However, most remain insufficiently active, and
      some become less active. Increasing PA, addressing pain, and treating asthma
      before surgery might have a positive effect on postoperative PA.

PMID- 21944953
TI  - HPV and head and neck cancer.
AB  - Head and neck cancer is frequent worldwide and oropharyngeal locations are
      presently sharply on the increase, in relation with an increasing incidence of
      oropharyngeal infection by oncogenic type-16 human papillomavirus (HPV). The
      clinical and biologic profile of these patients is distinct from that of other
      oropharyngeal carcinoma patients, with earlier onset, cystic cervical nodes and
      basaloid carcinoma histopathology. Detection of intratumoral viral DNA is
      essential to confirm the role of HPV, and E6/E7 mRNA expression is the most
      relevant indicator for stratification. Several methods can reveal intratumoral
      oncogenic HPV DNA, but PCR with hybridization is the most sensitive and most
      widely used. According to several reports, prognosis in terms of survival and
      locoregional control is better in HPV-positive oropharyngeal carcinoma than in
      oropharyngeal carcinoma associated with smoking and alcohol consumption. The
      future lies in vaccination, but further studies will determine whether the rate
      of oropharyngeal carcinoma falls in women vaccinated against cervical cancer.

PMID- 21944954
TI  - Elevated hair cortisol concentrations in endurance athletes.
AB  - Engaging in intensive aerobic exercise, specifically endurance sports, is
      associated with HPA axis activation indicated by elevated cortisol levels.
      Whether the repeated short-term elevations in cortisol levels result in higher
      long-term cortisol exposure of endurance athletes has been difficult to examine
      since traditional methods of cortisol assessments (saliva, blood, urine) reflect
      only relatively short time periods. Hair segment analysis provides a new method
      to assess cumulative cortisol secretion over prolonged time periods in a
      retrospective fashion. The aim of this study was to investigate cumulative
      cortisol secretion over several months reflecting intensive training and
      competitive races by examining hair cortisol levels of endurance athletes. Hair
      samples were obtained from 304 amateur endurance athletes (long-distance runners,
      triathletes, cyclists) and 70 controls. Cortisol concentrations were determined
      in the first to third 3-cm hair segments most proximal to the scalp. In addition,
      self-report measures of training volume were obtained. Endurance athletes
      exhibited higher cortisol levels in all three hair segments compared to controls
      (p<.001). Positive correlations between the cortisol concentration in the first
      hair segment and each indicator of training volume were found (all p<.01). These
      data suggest that repeated physical stress of intensive training and competitive
      races among endurance athletes is associated with elevated cortisol exposure over
      prolonged periods of time. These findings may have important implications with
      regard to somatic and mental health of athletes which should be investigated in
      future research.

PMID- 21944955
TI  - Changes in cortisol secretion during antidepressive treatment and cognitive
      improvement in patients with major depression: a longitudinal study.
AB  - OBJECTIVES: We have previously reported that cognitive deficits are cross
      sectionally associated with elevated cortisol in depressed patients. Here, we
      longitudinally examined if changes in cortisol secretion during treatment are
      associated with improvement of cognition. METHODS: Cognitive function and
      salivary cortisol levels were longitudinally examined in 52 patients with major
      depression before and after 3 weeks of standardized selective serotonin reuptake
      inhibitor (SSRI) and an add-on treatment modulating the mineralocorticoid
      receptor and compared to a healthy control group (n=50) matched for age, gender
      and years of education. RESULTS: Across add-on treatment groups, SSRI treatment
      reduced salivary cortisol in patients to levels of healthy controls (time*group
      interaction p=.05). In patients, reduction of cortisol significantly correlated
      with improvement in depressive symptoms (r=.52, p<.01), speed of information
      processing (r=.50, p<.01), and cognitive set-shifting (r=.34, p=.03). Improved
      depressive symptoms were only associated with improved attention and working
      memory. CONCLUSIONS: Improvement of some cognitive domains during SSRI treatment
      was associated with decreasing cortisol secretion and was only to a lesser extent
      associated with improved depressive symptoms.

PMID- 21944956
TI  - Response of glutathione system and carotenoids to sublethal copper in the
      postlarvae of Penaeus indicus.
AB  - The objective of this study is to determine the effect of sublethal copper on the
      glutathione system and carotenoids of Penaeus indicus postlarvae (PL) when
      subjected to short- and long-term exposure in the laboratory. The PL were exposed
      to 0.1641ppm (sublethal) copper for a period of 30 days with sampling intervals
      of 24, 48, 96h and 10, 20, 30 days. Variations in the activity of Glutathione
      reductase (GR), Glutathione peroxidase (GPx) and Glutathione-S-transferase
      (GSTase) were measured as biomarkers of toxicity. A significant (P<0.05) increase
      in the GR and GPx activity of the exposed PL till 20 days of exposure and
      thereafter a significant decrease indicates susceptibility of the PL to oxidative
      stress upon chronic exposure. Similarly, a significant decrease in GSTase
      activity during long-term exposures in the exposed PL reflects possible failure
      of the detoxification system. A possible role of carotenoids to combat oxidative
      stress against copper toxicity is also discussed.

PMID- 21944957
TI  - Biochemical response of anthracene and benzo [a] pyrene in milkfish Chanos
      chanos.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are common toxic pollutants found in the
      aquatic environment, and the assessment of their impact on biota is of
      considerable concern. The aim of the present research was to study the acute
      toxicity, bioaccumulation and biochemical response of milkfish Chanos chanos
      (Forsskal) to two selected PAHs: anthracene and benzo [a] pyrene. Acute toxicity
      test results were evaluated by the Probit analysis method and 96h LC(50) values
      for C. chanos exposed to anthracene was 0.030mgl(-1) and 0.014mgl(-1) for benzo
      [a] pyrene. Bioaccumulation concentration of anthracene was high when compared to
      benzo [a] pyrene. Biomarkers indicative of neurotoxicity (acetylcholinesterase,
      AchE), oxidative stress (lipid peroxidation, LPO and catalase, CAT) and phase II
      biotransformation of xenobiotics (glutathione S transferase, GST and reduced
      glutathione, GSH) were measured to assess effects of selected PAHs. Anthracene
      and benzo [a] pyrene increase LPO and CAT level of C. chanos suggesting that
      these PAHs may induce oxidative stress. Both the PAHs inhibited AchE indicating
      that they have at least one mechanism of neurotoxicity in common: the disruption
      of cholinergic transmission by inhibition of AChE. An induction of C. chanos
      glutathione S-transferase (GST) activity was found in fish exposed to benzo [a]
      pyrene, while an inhibition was observed after exposure to anthracene. These
      results suggest that GST is involved in the detoxification of benzo [a] pyrene,
      but not of anthracene.

PMID- 21944958
TI  - Immunotoxicity of 1-methyl-3-octylimidazolium bromide on brocarded carp (Cyprinus
      carpio L.).
AB  - In the present study, the immunotoxicity of 1-methyl-3-octylimidazolium bromide
      ([C(8)mim]Br) on brocarded carp was evaluated by an acute exposure of 100-300mgL(
      1) of [C(8)mim]Br for 7 days. The results showed 300mgL(-1) of [C(8)mim]Br
      exposure caused activity inhibition of specific and non-specific immune systems,
      mainly including IgM level, lysozyme activity, and complement C3 content, while
      100mgL(-1) of [C(8)mim]Br activated fish immune system during the early periods
      of exposure (2-5 days). This result indicates that [C(8)mim]Br has immunotoxicity
      on brocarded carp. Additionally, histological observation revealed that 300mgL(
      1) of [C(8)mim]Br-exposure led to remarkable damages to the hepatopancreas,
      kidney, and spleen of brocarded carp after 7 days of [C(8)mim]Br treatment,
      although not only change in kidney and spleen somatic indexes was found, but also
      no swelling or hemorrhage of carp viscera occurred.

PMID- 21944959
TI  - Prognostic factors for patients treated for a recurrent FIGO stage III ovarian
      cancer: a retrospective study of 108 cases.
AB  - AIMS: To determine overall survival of patients treated for a first relapse of
      FIGO stage III ovarian cancer, outside of randomized trial, with a long term
      follow-up and to identify prognostic factors. MATERIALS AND METHODS: A
      consecutive series of 108 patients treated for a first relapse of a FIGO stage
      III ovarian cancer was retrospectively included from December 1999 to November
      2004. Each patient was treated with platinum-based chemotherapy in case of late
      (>6 months) relapse and with salvage chemotherapy without platinum in case of <6
      months relapse. For statistical analysis the studied parameters were age,
      histological subtype, the completeness of initial surgery, disease-free period,
      localization of the relapse, clinical response to second-line chemotherapy, the
      completeness of secondary cytoreductive surgery (SCS) when it was performed.
      RESULTS: Median follow-up from the first relapse was 40 months. From the 108
      patients, 35 underwent SCS. Median overall survival from the first relapse was 13
      months in case of no SCS or non-optimal SCS and 35 months for patient with an
      optimal SCS (p = 0.006). In a multivariate analysis age, disease-free period, the
      clinical presentation of the relapse, completeness of SCS and response to second
      line chemotherapy appeared to be independent prognostic factors. CONCLUSIONS:
      Prognostic factors of ovarian cancer relapse are directly or indirectly linked
      with the feasibility of a complete SCS. Thus in the case of an ovarian cancer
      relapse, the feasibility of SCS must be considered in order to give the patient
      the best chance to experience its complete removal.

PMID- 21944960
TI  - Impact of CKD on coronary artery calcifications.

PMID- 21944961
TI  - Air pollution and coronary risk in kidney transplant recipients.

PMID- 21944964
TI  - The influence of age on the clinical features and outcomes of anti-glomerular
      basement membrane disease.

PMID- 21944962
TI  - Renal crescentic alpha heavy chain deposition disease: a report of 3 cases and
      review of the literature.
AB  - Heavy chain deposition disease (HCDD) is a comparatively recently described
      entity characterized by glomerular and tubular basement membrane deposition of
      monoclonal heavy chains without associated light chains. To our knowledge, review
      of the literature shows only 24 previously reported cases of HCDD with
      unequivocal evidence of monoclonal heavy chain deposition in the kidney using
      immunofluorescence microscopic and electron microscopic studies. The predominant
      heavy chain subtype was gamma. There has been a single case of MU HCDD and 2
      previously reported cases of alpha HCDD. In this report, we describe 3 additional
      cases of alpha HCDD, all with a crescentic pattern of injury and one of which was
      associated with cutis laxa. We compare their clinicopathologic features with all
      previously reported cases of HCDD.

PMID- 21944965
TI  - Missing data and multiple imputation when predicting mortality in incident
      dialysis patients.

PMID- 21944967
TI  - Does high or low urinary connective tissue growth factor predict CKD?

PMID- 21944969
TI  - Between a rock and a hard place.

PMID- 21944971
TI  - Synthesis and antitumor activity of beta-carboline 3-(substituted-carbohydrazide)
      derivatives.
AB  - A series of beta-carboline derivatives bearing a substituted-carbohydrazide
      moiety at C-3 were synthesized and evaluated for their antitumor activity against
      eight human cancer cell lines. The beta-carboline N-(substituted
      benzylidene)carbohydrazides showed, in general, a greater antitumor activity than
      their N-(alkylidene)carbohydrazide analogues. The N(9)-methylation of beta
      carboline N-(substituted-benzylidene) carbohydrazides resulted in a decrease of
      antitumor activity. Among compounds tested, the benzylidene-carbohydrazides 3, 4,
      11, 13, 16, 21 and 22 were the most active, possessing IC(50) less than 10 MUM
      for six of the eight tumor cell lines assayed. The derivative 4 displayed the
      most significant activity toward all tested cell lines, with a remarkable
      cytotoxicity against renal (786-0) cell lines (IC(50)=0.04 MUM). Compound 4 was
      assayed for its in vivo antineoplastic activity in the Ehrlich solid carcinoma
      assay.

PMID- 21944970
TI  - Quiz Page October 2011: An under-recognized cause of CKD.

PMID- 21944972
TI  - The anti-malarial activity of bivalent imidazolium salts.
AB  - A series of compounds containing bivalent imidazolium rings and one triazolium
      analog were synthesized and evaluated for their ability to inhibit the
      replication of Plasmodium falciparum cultures. The activity and selectivity of
      the compounds for P. falciparum cultures were found to depend on the presence of
      electron-deficient rings that were spaced an appropriate distance apart. The
      activity of the compounds was not critically dependent on the nature of the
      linker between the electron-deficient rings, an observation that suggests that
      the rings were responsible for the primary interaction with the molecular target
      of the compounds in the parasite. The bivalent imidazolium and triazolium
      compounds disrupted the process whereby merozoites gain entry into erythrocytes,
      however, they did not appear to prevent merozoites from forming. The compounds
      were also found to be active in a murine Plasmodium berghei infection, a result
      consistent with the compounds specifically interacting with a parasite component
      that is required for replication and is conserved between two Plasmodium species.

PMID- 21944973
TI  - Design, structure-activity relationship, and highly efficient asymmetric
      synthesis of 3-phenyl-4-benzylaminopiperidine derivatives as novel neurokinin-1
      receptor antagonists.
AB  - We synthesized a series of novel 3-phenyl-4-benzylaminopiperidine derivatives
      that were identified as potent tachykinin NK(1) receptor antagonists by
      structural modification of the 3-benzhydrylpiperidone derivative through high
      throughput screening. N-{2-[(3R,4S)-4-({2-Methoxy-5-[5-(trifluoromethyl)-1H
      tetrazol-1-yl]benzyl}amino)-3-phenyl-1-piperidinyl]-2-oxoethyl}acetamide ((+)-39)
      was found to be one of the most potent tachykinin NK(1) receptor antagonists with
      high metabolic stability. Highly efficient asymmetric synthesis of (+)-39 was
      achieved via dynamic kinetic resolution.

PMID- 21944974
TI  - Molecular pathology of MELAS and L-arginine effects.
AB  - BACKGROUND: The pathogenic mechanism of stroke-like episodes seen in
      mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes
      (MELAS) has not been clarified yet. About 80% of MELAS patients have an A3243G
      mutation in the mitochondrial tRNA(Leu(UUR)) gene, which is the base change at
      position 14 in the consensus structure of tRNA(Leu(UUR)) gene. SCOPE OF REVIEW:
      This review aims to give an overview on the actual knowledge about the pathogenic
      mechanism of mitochondrial cytopathy at the molecular levels, the possible
      pathogenic mechanism of mitochondrial angiopathy to cause stroke-like episodes at
      the clinical and pathophysiological levels, and the proposed site of action of l
      arginine therapy on MELAS. MAJOR CONCLUSIONS: Molecular pathogenesis is mainly
      demonstrated using rho(0) cybrid system. The mutation creates the protein
      synthesis defects caused by 1) decreased life span of steady state amount of
      tRNA(Leu(UUR)) molecules; 2) decreased ratio of aminoacyl-tRNA(Leu(UUR)) versus
      uncharged tRNA(Leu(UUR)) molecules; 3) the accumulation of aminoacylation with
      leucine without any misacylation; 4) accumulation of processing intermediates
      such as RNA 19, 5) wobble modification defects. All of these loss of function
      abnormalities are created by the threshold effects of cell or organ to the
      mitochondrial energy requirement when they establish the phenotype. Mitochondrial
      angiopathy demonstrated by muscle or brain pathology, as SSV (SDH strongly
      stained vessels), and by vascular physiology using FMD (flow mediated dilation).
      MELAS patients show decreased capacity of NO dependent vasodilation because of
      the low plasma levels of l-arginine and/or of respiratory chain dysfunction.
      Although the underlying mechanisms are not completely understood in stroke-like
      episodes in MELAS, l-arginine therapy improved endothelial dysfunction. GENERAL
      SIGNIFICANCE: Though the molecular pathogenesis of an A3243G or T3271C mutation
      of mitochondrial tRNA(Leu(UUR)) gene has been clarified as a mitochondrial
      cytopathy, the underlying mechanisms of stroke-like episodes in MELAS are not
      completely understood. At this point, l-arginine therapy showed promise in
      treating of the stroke-like episodes in MELAS. This article is part of a Special
      Issue entitled Biochemistry of Mitochondria.

PMID- 21944976
TI  - Evans syndrome and systemic lupus erythematosus: clinical presentation and
      outcome.
AB  - OBJECTIVE: To review the clinical, laboratory and outcome features of Evans
      syndrome (ES) in systemic lupus erythematosus (SLE) patients. METHODS: We
      reviewed the charts of 953 SLE patients followed up regularly at our service. ES
      was defined as the presence of hemolytic anemia and thrombocytopenia
      concomitantly or sequentially. Clinical and laboratory manifestations occurring
      during the disease course, as well as concomitant diseases and survival was
      carefully reviewed. RESULTS: We identified ES in 26 of 953 (2.7%) SLE patients.
      Twenty-three were women with mean age at SLE diagnosis of 25.7 years. Four (15%)
      patients had disease onset before the age of 16. In the majority of patients
      (92%), immune thrombocytopenia and AIHA appeared simultaneously at the beginning
      of SLE. Active features of SLE were a frequent finding concomitant to ES,
      especially arthritis (77%), malar rash (61.5%), photosensitivity (57.6%), oral
      ulcers (34.6%), nephritis (73%), serositis (54%), neuropsychiatric (19%) and
      pulmonary (15%) manifestations. In addition to this multisystemic disease, 34.6%
      of our patients had an association with another autoimmune disease such as
      antiphospholipid syndrome. Recurrence of ES was observed in only four (15%)
      patients. After follow-up time of 8.72 years, 19 patients (73%) were in remission
      and seven (27%) patients died. DISCUSSION: ES is a rare manifestation in SLE,
      occurring in patients with severe multisystemic SLE manifestations. Treatment
      strategies frequently used in SLE contribute to longer disease remission and less
      frequent exacerbation than observed in the general population with ES.

PMID- 21944975
TI  - Obesity, metabolic dysregulation and oxidative stress in asthma.
AB  - BACKGROUND: Epidemiological data demonstrate an increased risk of developing
      incident asthma with increasing adiposity. While the vast majority of studies
      support the interaction between obesity and asthma, the causality is unclear.
      SCOPE OF REVIEW: This article will review the current literature supporting the
      presence of an obese asthma phenotype and the possible mechanisms mediating the
      effects of obesity on asthma. MAJOR CONCLUSIONS: Obesity is associated with poor
      asthma control, altered responsiveness to medications and increased morbidity.
      Obesity is characterized by systemic inflammation that may result in increased
      airway inflammation. However, this assertion is not supported by current studies
      that demonstrate a lack of significant airway inflammation in obese asthmatics.
      In spite this observation one must consider limitations of these studies
      including the fact that most subjects were treated with inhaled corticosteroids
      that would likely alter inflammation in the lung. Thus, it remains unclear if
      obesity is associated with alterations in inflammation in the airways of subjects
      with asthma. Hormones such as leptin and adiponectin are affected by obesity and
      may play a role in mediating innate immune responses and allergic responses,
      respectively. The role of oxidative stress remains controversial and the current
      evidence suggests that while oxidative stress is important in asthma, it does not
      fully explain the characteristics associated with this unique phenotype. GENERAL
      SIGNIFICANCE: Obesity related asthma is associated with increased morbidity and
      differential response to asthma therapies. Understanding the mechanisms mediating
      this phenotype would have significant implications for millions of people
      suffering with asthma. This article is part of a Special Issue entitled
      Biochemistry of Asthma.

PMID- 21944977
TI  - Lepromatous leprosy presenting as an acute polyarthritis in a Colombian immigrant
      in Spain.

PMID- 21944978
TI  - Chronic expanding hematoma of the thigh.
AB  - Hematomas following surgery or trauma usually resolve without complications. In
      some instances, for reasons that are not completely understood, hematoma
      formation is followed by slow expansion of the mass. The large fluid collection
      is surrounded by a pseudocapsule and fibrous tissue, and present months or years
      after the original insult, as chronic expanding hematoma. In this case study, we
      present a rare case of chronic expanding hematoma in an 84-year-old woman. The
      patient noted a painful swelling in the posteromedial aspect of the lower thigh,
      and recalled a bump to the left knee 64 years earlier. The lesion was
      successfully resected, with a preoperative presumptive diagnosis of organized
      hematoma, although the clinical findings were suggestive of malignancy. We
      describe the radiological findings, discuss the differential diagnosis.

PMID- 21944979
TI  - Reactivation of resolved hepatitis B during rituximab therapy for rheumatoid
      arthritis.

PMID- 21944980
TI  - Effectiveness of the end-range mobilization and scapular mobilization approach in
      a subgroup of subjects with frozen shoulder syndrome: a randomized control trial.
AB  - Treatment strategies targeting abnormal shoulder kinematics may prevent pathology
      or if the pathology develops, shorten its duration. We examined the effectiveness
      of the end-range mobilization/scapular mobilization treatment approach (EMSMTA)
      in a subgroup of subjects with frozen shoulder syndrome (FSS). Based on the
      kinematics criteria from a prediction method, 34 subjects with FSS were
      recruited. Eleven subjects were assigned to the control group, and 23 subjects
      who met the criteria were randomly assigned to the criteria-control group with a
      standardized physical therapy program or to the EMSMTA group. Subjects attended
      treatment sessions twice a week for 8 weeks. Range of motion (ROM), disability
      score, and shoulder complex kinematics were obtained at the beginning, 4 weeks,
      and 8 weeks. Subjects in the EMSMTA group experienced greater improvement in
      outcomes compared with the criteria-control group at 4 weeks (mean difference=0.2
      of normalized hand-behind-back reach) and 8 weeks (mean difference=22.4 degrees
      humeral external rotation, 0.31 of normalized hand-behind-back reach, 7.5
      disability, 5 degrees tipping and 0.32 rhythm ratio). Similar improvements were
      found between the EMSMTA group and control group. The EMSMTA was more effective
      than a standardized physical therapy program in a subgroup of subjects who fit
      the criteria from a prediction method.

PMID- 21944981
TI  - Atrophy of the prostate on needle biopsy and false-positive diagnosis of
      malignancy.

PMID- 21944982
TI  - Waldenstrom's macroglobulinemia presenting as a perinephric mass.

PMID- 21944983
TI  - The search for a better prostate cancer biomarker.

PMID- 21944984
TI  - Re: Administrative data sets are inaccurate for assessing functional outcomes
      after radical prostatectomy: M. K. Tollefson, M. T. Gettman, R. J. Karnes and I.
      Frank J Urol 2011; 185: 1686-1690.

PMID- 21944986
TI  - Editorial comment.

PMID- 21944987
TI  - Editorial comment.

PMID- 21944988
TI  - Editorial comment.

PMID- 21944989
TI  - External validation of the Leibovich prognosis score for nonmetastatic clear cell
      renal cell carcinoma at a single European center applying routine pathology.
AB  - PURPOSE: The Leibovich prognosis score was developed as a prognostic tool for
      metastatic disease after radical nephrectomy for clear cell renal cell carcinoma
      using pathology review. However, this scoring system has never been externally
      validated. We externally validated its prognostic accuracy using routine
      pathology reports. MATERIALS AND METHODS: We retrospectively evaluated data from
      the routine pathology records of 1,754 consecutive patients with nonmetastatic
      clear cell renal cell carcinoma operated on between 1984 and 2006 at a single
      tertiary academic center. Clear cell renal cell carcinoma cases were categorized
      as 0 to 11 by the Leibovich prognosis score and further stratified into low,
      intermediate and high risk groups. Metastasis-free survival was assessed using
      the Kaplan-Meier method. To evaluate the prognostic impact a multivariate Cox
      regression model was used and prognostic accuracy was determined using Harrell's
      concordance index. RESULTS: Median followup was 82 months (IQR 39-142).
      Metastasis developed in 375 of the 1,754 patients (21.4%). The 10-year metastasis
      free survival rate for Leibovich scores in our study ranged from 95% for scores
      of 0 and 1 to 12% for scores of 8 or greater. Pathological T stage, N stage, low
      tumor grade, large tumor diameter and histological tumor necrosis were
      independent predictors of metastasis-free survival (p <0.001). Harrell's
      concordance index was 0.778. CONCLUSIONS: Risk prediction by the Leibovich
      prognosis score using routine pathological results was comparable to that of the
      original data based on pathology review. Our data support using the Leibovich
      prognosis score in clinical practice for followup decisions and patient selection
      for adjuvant treatment trials.

PMID- 21944990
TI  - Comparison of outpatient narcotic prescribing patterns after minimally invasive
      versus retropubic and perineal radical prostatectomy.
AB  - PURPOSE: Studies comparing pain after minimally invasive vs retropubic and
      perineal radical prostatectomy are conflicting. We characterized population based
      outpatient narcotic prescribing patterns after minimally invasive, retropubic and
      perineal radical prostatectomy. MATERIALS AND METHODS: We evaluated outpatient
      prescription data after minimally invasive, retropubic and perineal radical
      prostatectomy from 2003 to 2006 using MarketScan(r). Baseline and postoperative
      narcotic prescriptions were identified using the National Drug Code. Total
      prescribed narcotic strength in morphine sulfate equivalents, the number of
      prescriptions filled and costs were compared. We performed multivariate analysis
      adjusted for surgical approach, age, comorbidity, baseline narcotic use, health
      plan and geographic region. RESULTS: We identified 2,206 minimally invasive,
      8,037 retropubic and 463 perineal radical prostatectomies with no differences in
      baseline narcotic prescription use. Perineal and retropubic operations were
      associated with greater total morphine sulfate equivalent use than the minimally
      invasive operation. Perineal prostatectomy was associated with more narcotic
      refills than minimally invasive and retropubic prostatectomy (42.3% vs 20.2% and
      28.9%, respectively, p <0.001). Median narcotic costs were lower for minimally
      invasive than for perineal and retropubic prostatectomy. On adjusted analysis
      perineal radical prostatectomy, younger age, baseline narcotic use and preferred
      provider organization health plan were associated with greater morphine sulfate
      equivalents and narcotic refills while minimally invasive surgery was associated
      with fewer refills and lower costs but not with total morphine sulfate
      equivalents. There was significant geographic variation in narcotic use and
      costs. CONCLUSIONS: Postoperatively minimally invasive radical prostatectomy
      required fewer narcotic refills and had lower narcotic costs while perineal
      radical prostatectomy required the greatest amount of narcotics. However,
      minimally invasive vs retropubic radical prostatectomy morphine sulfate
      equivalent requirements did not differ on adjusted analysis. While our findings
      support the purported advantage of minimally invasive radical prostatectomy of
      less postoperative pain, confirmatory prospective studies with objective outcomes
      are needed.

PMID- 21944991
TI  - Outpatient surgery for vesicoureteral reflux: endoscopic injection vs
      extravesical ureteral reimplantation.

PMID- 21944992
TI  - Reconstruction of the acoustic impedance profile in a plate using an inverse
      spectral procedure.
AB  - An inverse spectral procedure was applied to reconstruct the acoustic impedance
      profile along the thickness direction of a plate using its thickness resonance
      frequencies, density and thickness. For a successful reconstruction, the material
      property profile must be symmetric about the mid-plane of the plate. Several
      cases of numerical simulations, including plates with a few layers and with a
      high number of layers are described. The calculated resonance frequencies were
      used to reconstruct the acoustic impedance profile, a process that was successful
      for all cases. We assume that a plate with a high number of layers, each with a
      different but constant acoustic impedance, simulates a plate with a smoothly
      varying acoustic impedance profile. It can be concluded that such a plate, which
      generates small, virtually undetectable, internally reflected waves, can also be
      reconstructed. In the special case of a plate of unknown thickness and unknown
      but constant density, the method is still useful, because a relative variation of
      the material property can be reconstructed using only the resonance frequencies.
      An experiment using a resonance-mode electromagnetic acoustic transducer
      (resonance-mode EMAT) is also described. EMAT is a non-contact ultrasonic method
      that can measure thickness resonance frequencies, making it appropriate for this
      method. Some examples of applications are measurement of the temperature profile
      inside a rolled metal sheet, measurement of a clad metal plate, and monitoring of
      a metal casting.

PMID- 21944993
TI  - Noninvasive estimation of the ocular elastic modulus for age-related macular
      degeneration in the human eye using sequential ultrasound imaging.
AB  - INTRODUCTION: Elastic modulus estimation may be an important clinical criterion,
      as it seems to affect such eye parameters as intraocular pressure, ocular
      pulsation, blood flow, effect of topical medications, and post-refractive surgery
      complications. The purpose of this study was to examine the differences in
      elasticity in the ocular axial length, posterior wall thickness (posterior pole),
      and retina-choroid thickness under normal and aged-related macular degeneration
      (AMD) conditions in the human eye by directly estimating the elastic modulus with
      sequential and noninvasive ultrasound image processing. MATERIALS AND METHODS: In
      this study, 25 healthy subjects and 20 patients with non-neovascular AMD
      participated in the experiment. The deformation of the ocular axial length,
      posterior wall thickness and retina-choroid complex thickness was captured using
      high-resolution ultrasonography before and after loading. The B-mode (20MHz) and
      A-mode (8MHz) frames were obtained and processed with an echo tracking technique.
      The elastic modulus was estimated using changes in ocular axial length, posterior
      wall thickness and retina-choroid complex thickness and with applied stress
      measurements. RESULTS: There was a significant difference (p<0.05) in the ocular
      axial length elastic modulus between the AMD and healthy subjects (AMD patients:
      95.165+/-26.431kPa, vs. healthy subjects: 49.539+/-25.867kPa). Moreover, there
      was a statistically significant difference (p<0.05) in the posterior wall
      thickness elastic modulus between AMD patients and healthy subjects (AMD
      patients: 50.519+/-12.295kPa, vs. healthy subjects: 20.519+/-11.827kPa). However,
      no statistically significant difference (p-value>0.05) was found in the retina
      choroid complex elastic modulus between the two groups (AMD patients: 20.134+/
      3.898kPa, vs. healthy subjects: 15.630+/-4.250kPa). CONCLUSION: Although the
      results were obtained examining a relatively low number of patients, it would
      appear that noninvasive ultrasound estimation of the local elastic moduli of
      ocular axial length and posterior wall thickness is suited to aid in detection of
      the non-exudative AMD thus manifesting its potential as a screening tool in
      symptom-free individuals.

PMID- 21944994
TI  - A theoretical study of the propagation of Rayleigh waves in a functionally graded
      piezoelectric material (FGPM).
AB  - An exact approach is used to investigate Rayleigh waves in a functionally graded
      piezoelectric material (FGPM) layer bonded to a semi infinite homogenous solid.
      The piezoelectric material is polarized when the six fold symmetry axis is put
      along the propagation direction x(1). The FGPM character imposes that the
      material properties change gradually with the thickness of the layer. Contrary to
      the analytical approach, the adopted numerical methods, including the ordinary
      differential equation (ODE) and the stiffness matrix method (SMM), treat
      separately the electrical and mechanical gradients. The influences of graded
      variations applied to FGPM film coefficients on the dispersion curves of Rayleigh
      waves are discussed. The effects of gradient coefficients on electromechanical
      coupling factor, displacement fields, stress distributions and electrical
      potential, are reported. The obtained deviations in comparison with the ungraded
      homogenous film are plotted with respect to the dimensionless wavenumber.
      Opposite effects are observed on the coupling factor when graded variations are
      applied separately. A particular attention has been devoted to the maximum of the
      coupling factor and it dependence on the stratification rate and the gradient
      coefficient. This work provides with a theoretical foundation for the design and
      practical applications of SAW devices with high performance.

PMID- 21944995
TI  - Analysis of transcriptional regulation of tetracycline responsive genes in Brugia
      malayi.
AB  - The Wolbachia endosymbiont of the human filarial parasites is necessary for
      parasite reproduction, making it an attractive chemotherapeutic target. Previous
      studies have demonstrated that mRNA levels of several nuclearly encoded genes are
      altered as a result of exposure to antibiotics that eliminate the endosymbiont,
      suggesting that they may be involved in maintaining the parasite-endosymbiont
      relationship. Here, we tested the hypothesis that the increase in mRNA levels of
      certain nuclearly encoded genes of Brugia malayi in response to tetracycline
      treatment involved specific regulatory elements present in the promoters of these
      genes. The promoters of three such genes (BmRPL13, BmRPS4 and BmHSP70) were
      tested for tetracycline responsiveness utilizing a homologous transient
      transcription system. Reporter gene expression driven by all three promoters was
      up-regulated in transfected embryos exposed to tetracycline. Substitution
      mutagenesis was employed to map the cis-acting elements responsible for this
      response in the BmHSP70 promoter. Tetracycline responsiveness was found to be
      distinct from the cis-acting elements involved in regulating the stress response
      from the BmHSP70 promoter; rather, tetracycline responsiveness was mediated by a
      TATAA-box like element. This study represents the first demonstration of small
      molecule-mediated gene regulation of a native B. malayi promoter.

PMID- 21944996
TI  - CCSVI: is blinding the key?

PMID- 21944997
TI  - Effects of myeloablation, peripheral chimerism, and whole-body irradiation on the
      entry of bone marrow-derived cells into the brain.
AB  - Understanding how bone marrow-derived cells (BMDCs) enter the central nervous
      system (CNS) is critical for the development of therapies for brain-related
      disorders using hematopoietic stem cells. We investigated the brain damages and
      blood-brain barrier (BBB) modification following  either whole-body irradiation
      or a myeloablative chemotherapy regimen in mice, and the capacity for these
      treatments to induce the entry of BMDCs into the CNS. Neither treatment had a
      lasting effect on brain integrity and both were equally efficient at achieving
      myeloablation. Injection of  bone marrow cells from green fluorescent protein
      (GFP) transgenic mice was able to completely repopulate the hematopoietic niche
      in the circulation and in hematopoietic organs (thymus and spleen). However,
      GFP(+) cells only entered the brain following whole-body irradiation. We conclude
      that myeloablation, damages to the brain integrity, or the BBB and peripheral
      chimerism are not responsible for the entry of BMDCs into the CNS following
      irradiation.

PMID- 21944998
TI  - Dysfunctional HDL containing L159R ApoA-I leads to exacerbation of
      atherosclerosis in hyperlipidemic mice.
AB  - The mutation L159R apoA-I or apoA-I(L159R) (FIN) is a single amino acid
      substitution within the sixth helical repeat of apoA-I. It is associated with a
      dominant negative phenotype, displaying hypoalphaproteinemia and an increased
      risk for atherosclerosis in humans. Mice lacking both mouse apoA-I and LDL
      receptor (LDL(-/-), apoA-I(-/-)) (double knockout or DKO) were crossed>9
      generations with mice transgenic for human FIN to obtain L159R apoA-I, LDLr(-/-),
      ApoA-I(-/-) (FIN-DKO) mice. A similar cross was also performed with human wild
      type (WT) apoA-I (WT-DKO). In addition, FIN-DKO and WT-DKO were crossed to obtain
      WT/FIN-DKO mice. To determine the effects of the apoA-I mutations on
      atherosclerosis, groups of each genotype were fed either chow or an atherogenic
      diet for 12weeks. Interestingly, the production of dysfunctional HDL-like
      particles occurred in DKO and FIN-DKO mice. These particles were distinct with
      respect to size, and their enrichment in apoE and cholesterol esters. Two
      dimensional gel electrophoresis indicated that particles found in the plasma of
      FIN-DKO mice migrated as large alpha(3)-HDL. Atherosclerosis analysis showed that
      FIN-DKO mice developed the greatest extent of aortic cholesterol accumulation
      compared to all other genotypes, including DKO mice which lack any apoA-I. Taken
      together these data suggest that the presence of large apoE enriched HDL
      particles containing apoA-I L159R lack the normal cholesterol efflux promoting
      properties of HDL, rendering them dysfunctional and pro-atherogenic. In
      conclusion, large HDL-like particles containing apoE and apoA-I(L159R) contribute
      rather than protect against atherosclerosis, possibly through defective efflux
      properties and their potential for aggregation at their site of interaction in
      the aorta. This article is part of a Special Issue entitled Advances in High
      Density Lipoprotein Formation and Metabolism: A Tribute to John F. Oram (1945
      2010).

PMID- 21944999
TI  - Inference of Granger causal time-dependent influences in noisy multivariate time
      series.
AB  - Inferring Granger-causal interactions between processes promises deeper insights
      into mechanisms underlying network phenomena, e.g. in the neurosciences where the
      level of connectivity in neural networks is of particular interest. Renormalized
      partial directed coherence has been introduced as a means to investigate Granger
      causality in such multivariate systems. A major challenge in estimating
      respective coherences is a reliable parameter estimation of vector autoregressive
      processes. We discuss two shortcomings typical in relevant applications, i.e. non
      stationarity of the processes generating the time series and contamination with
      observational noise. To overcome both, we present a new approach by combining
      renormalized partial directed coherence with state space modeling. A numerical
      efficient way to perform both the estimation as well as the statistical inference
      will be presented.

PMID- 21945001
TI  - Two ways to use imaging: focusing directly on mechanism, or indirectly via
      behaviour?
AB  - Recent developments in mesoscopic imaging--imaging at the level of tissues and
      organs, rather than the subcellular or molecular scale--are proving to be
      powerful for developmental biology. At the same time, these developments are also
      helping to emphasize an important distinction between two quite different
      approaches of how imaging is used. In the more traditional approach, images
      provide a direct insight into how a systems works-suggesting a mechanism or part
      of a mechanism. However an alternative approach is gaining ground, in which
      imaging is used to quantify the behaviour of a system, rather than directly
      assessing the mechanism. In this case the causal relationships of a system are
      inferred in a more indirect way-by comparing quantitative measurements with
      mathematical models of the system in question. Although indirect, this approach
      is powerful for addressing more complex biological systems--especially multiscale
      problems. It is tempting to distinguish the latter approach with the label
      'quantitative biology', but this term only emphasizes the use of numbers, and
      therefore obscures the more fundamental difference, which is the powerful but
      indirect nature of the approach. Here I will discuss the distinction between the
      two imaging approaches, particularly in the context of recent improvements to
      tissue-level imaging techniques.

PMID- 21945000
TI  - Selective, quantitative measurement of releasable synaptic zinc in human autopsy
      hippocampal brain tissue from Alzheimer's disease patients.
AB  - Aberrant central nervous system zinc homeostasis has been reported in Alzheimer's
      disease (AD). However, there are conflicting reports describing zinc
      concentration either increased or decreased in the brain of AD patients. Such
      discrepancies may be due to differences in the brain area examined, zinc
      detection method, and/or tissue composition. Furthermore, detection and
      measurement of the releasable zinc pool in autopsy tissue is difficult and
      usually unreliable. Obtaining an adequate assessment of this releasable zinc pool
      is of particular significance in AD research in that zinc can coordinate with and
      stabilize toxic amyloid beta oligomers, which are believed to play a key role in
      AD neuropathology. In addition, zinc released into the synaptic cleft can
      interact with the postsynaptic neurons causing altered signaling and synaptic
      dysfunction, which is a well established event in AD. The method presented here
      combines two approaches, biochemical fractionation and atomic absorption
      spectrophotometry, to allow, in addition to extracellular zinc concentration, the
      reliable and quantitative measurement of zinc specifically localized in synaptic
      vesicles, which contain the majority of the neuronal releasable zinc. Using this
      methodology, we found that synaptic vesicle zinc concentrations were increased in
      AD hippocampi compared to age-matched controls and that this increase in
      releasable zinc matched increased concentration of zinc in the extracellular
      space.

PMID- 21945002
TI  - Label-free imaging of lipid dynamics using Coherent Anti-stokes Raman Scattering
      (CARS) and Stimulated Raman Scattering (SRS) microscopy.
AB  - The recently developed Coherent Anti-stokes Raman Scattering (CARS) microscopy
      and Stimulated Raman Scattering (SRS) microscopy have provided new methods to
      visualize the localization and regulation of biological molecules without the use
      of invasive and potentially perturbative labels. They allow rapid imaging of
      specific molecules with high resolution and sensitivity. These tools have been
      effectively applied to the study of lipid metabolism using Caenorhabditis elegans
      as a genetic model, unraveling new lipid storage phenotypes and their regulatory
      mechanisms. Here we review the underlying principle of CARS and SRS microscopy,
      as well as their recent applications in lipid biology research in C. elegans.

PMID- 21945003
TI  - Protective effects of ginsenoside Rd against okadaic acid-induced neurotoxicity
      in vivo and in vitro.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng, a traditional Chinese herbal
      medicine, has been widely used to restore the disease and enhance the healthy
      body in Asia for about 5000 years. The present study aimed to investigate the
      possible neuroprotective effects of ginsenoside Rd against OA-induced toxicity.
      MATERIALS AND METHODS: Ginsenoside Rd was used in tauopahy models of Alzheimer's
      disease (AD). To mimic the in vivo or in vitro tau hyperphosphorylation, okadaic
      acid (OA), a protein phosphatase inhibitor, was bilaterally micro-infused into
      the cerebral ventricle of adult male Sprague-Dawley (SD) rats, or added in media
      of cultured cortical neurons. The phosphorylation levels of tau and the
      activities of protein phosphatase 2A (PP-2A) were measured and compared with
      ginsenoside Rd pretreated groups. RESULTS: Pretreatment with ginsenoside Rd in SD
      rats (10mg/kg for 7 days) or in cultured cortical neurons (2.5 or 5MUmol/L for
      12h) reduced OA-induced neurotoxicity and tau hyperphosphorylation by enhancing
      the activities of PP-2A. CONCLUSIONS: The result of the present work implied that
      ginsenoside Rd protected SD rats and cultured cortical neurons against OA-induced
      toxicity. The possible neuroprotective mechanism may be that ginsenoside Rd
      decreases OA-induced the hyperphosphorylation of tau by the increase in
      activities of PP-2A. Thus, this study promises that ginsenoside Rd might be a
      potential preventive drug candidate for AD and other tau pathology-related
      neuronal degenerative diseases.

PMID- 21945004
TI  - Phospho-flow cytometry based analysis of differences in T cell receptor signaling
      between regulatory T cells and CD4+ T cells.
AB  - CD4+ T regulatory cells (Tregs) are activated during auto-immune, injury, and
      inflammatory responses, however, the molecular events that trigger Treg
      activation are poorly understood. The purpose of this study was to investigate
      whether Tregs (FoxP3+ CD4+ T cells) and non-Treg CD4+ T cells might display
      differences in T cell receptor (TCR) dependent signaling responses following in
      vitro or in vivo stimulation. This study used phospho-flow cytometry as a tool to
      profile the kinetics and extent of TCR signaling (ZAP-70 and PKC-theta
      phosphorylation and expression) in Tregs and non-Tregs. We found that in vitro
      stimulation with anti-CD3epsilon induces early and transient activation of ZAP-70
      and PKC-theta in both Tregs and non-Tregs. However, the response in Tregs was
      more rapid and higher in magnitude than responses seen in non-Tregs. In contrast,
      bacterial superantigen or antigen-specific TCR stimulation did not significantly
      activate these signaling pathways in Tregs or non-Tregs. Additional experiments
      tested the kinetics of in vivo TCR signaling in Tregs and non-Tregs in mice
      challenged with bacterial superantigen. The results of these experiments showed
      that superantigen rapidly activated ZAP-70 and PKC-theta in lymph node Tregs, but
      not in non-Tregs. In summary, we demonstrate the versatility of using phospho
      flow cytometry to measure cell signaling in CD4+ T cells. The results of these in
      vitro and in vivo studies demonstrate that Tregs and non-Treg CD4+ T cells show
      marked differences in their reactivity to TCR-dependent stimulation and
      contribute new insights into basic mechanisms that lead to Treg activation.

PMID- 21945006
TI  - Molecular network of microRNA targets in Alzheimer's disease brains.
AB  - MicroRNAs (miRNAs) are a group of small noncoding RNAs that regulate
      translational repression of target mRNAs. The vast majority of presently
      identified miRNAs are expressed in the brain where they fine-tune the expression
      of a wide range of target molecules essential for neuronal and glial development,
      differentiation, proliferation, apoptosis and metabolism. Aberrant expression and
      dysfunction of brain-enriched miRNAs induce development of neurodegenerative
      diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). Because
      a single miRNA concurrently downregulates hundreds of target mRNAs, the set of
      miRNA target genes coregulated by an individual miRNA generally constitutes the
      biologically integrated network of functionally associated molecules. Recent
      advances in systems biology enable us to characterize the global molecular
      network of experimentally validated targets for individual miRNAs by using
      pathway analysis tools of bioinformatics endowed with comprehensive
      knowledgebase. This review is conducted to summarize accumulating studies focused
      on aberrant miRNA expression in AD brains, and to propose the systems biological
      view that abnormal regulation of cell cycle progression as a result of
      deregulation of miRNA target networks plays a central role in the pathogenesis of
      AD.

PMID- 21945005
TI  - Prenatal nicotine exposure alters postnatal cardiorespiratory integration in
      young male but not female rats.
AB  - The present study tested the hypothesis that prenatal nicotine exposure (PNE)
      induces sex specific alternations in indices of cardiorespiratory coupling during
      early development. Rat pups exposed to either nicotine (6 mg/kg/day) or saline
      (control) in utero were chronically instrumented with ECG electrodes for
      measurement of heart rate (HR) and respiratory frequency (RF) was monitored by
      whole body plethysmography on postnatal days (P)13, P16 and P26. PNE had no
      identifiable effect on resting respiratory frequency (RF) in either sex. There
      was however a strong trend (p=0.057) for resting HR to be elevated by PNE in male
      offspring only. Alternatively, the HR response to hypoxia (10% O(2)), was
      significantly blunted at P13 but significantly elevated at P26 s in the absence
      of any significant change in RF in PNE males only. Indicators of respiratory
      sinus arrhythmia (RSA) were also significantly reduced in P26 PNE males. No
      significant effects of PNE on HR, RF or RSA were identified in female offspring
      at any age. Our results demonstrate that PNE induces very specific changes in
      cardiorespiratory integration at select postnatal ages and these changes are more
      prominent in males. Additionally, alternations in cardiorespiratory integration
      appear to persist into later development in males only, potentially increasing
      the risk for cardiovascular diseases such as hypertension later in life.

PMID- 21945007
TI  - Mesenchymal stem cells for peripheral nerve regeneration--a real hope or just an
      empty promise?

PMID- 21945008
TI  - Anti-inflammatory cytokines, TGF-beta1 and IL-10, exert anti-hypoxic action and
      abolish posthypoxic hyperexcitability in hippocampal slice neurons: comparative
      aspects.
AB  - The aim of this study was to investigate the comparative effects of transforming
      growth factor beta1 (TGF-beta1) and interleukin-10 (IL-10) on the repeated brief
      hypoxia-induced alterations in the activity of hippocampal slice CA1 pyramidal
      neurons. The method of field potentials measurement in CA1 region of hippocampal
      slices was used. The principal results of our work are summarized as follow. 1.
      TGF-beta1 reduces the depressive effect of brief hypoxia on the population spike
      amplitude more effectively than IL-10. 2. During TGF-beta1 exposure (in contrast
      to IL-10), three 3-min hypoxic episodes do not induce the rapid hypoxic
      preconditioning. 3. TGF-beta1 and IL-10 equally abolish posthypoxic
      hyperexcitability induced by repeated brief episodes of hypoxia in CA1 pyramidal
      neurons. These findings indicated that TGF-beta1 and IL-10 are able to evoke anti
      hypoxic effect and abolish the development of posthypoxic hyperexcitability
      induced by repeated brief hypoxic episodes in hippocampal CA1 pyramidal neurons.
      Our results also demonstrated that TGF-beta1 reduced the effectiveness of hypoxia
      to depress neuronal activity more effectively than IL-10. We suggest that the
      present findings allow to explain the certain neuroprotective mechanisms of IL-10
      and TGF-beta1 in the early phase of hypoxia and indicate that a therapeutic anti
      inflammatory approach using these substances can provide neuroprotection in the
      brain hypoxic conditions.

PMID- 21945009
TI  - [The 18th meeting of the Societe Francophone d'Informatique et de Monitorage en
      Anesthesie-Reanimation (Sfimar)].

PMID- 21945010
TI  - Predicting university undergraduates' binge-drinking behavior: a comparative test
      of the one- and two-component theories of planned behavior.
AB  - This study provides a comparative test of the one- and two-component theories of
      planned behavior (TPB) in the context of university undergraduates' binge
      drinking. Participants (N=120) self-completed questionnaire measures of all TPB
      constructs at time 1 and subsequent binge-drinking at time 2 (two-weeks later).
      The data were analyzed using a combination of path analyses and bootstrapping
      procedures. Both models accounted for a substantial proportion of the variation
      in behavior. However, the two-component TPB provided a significantly better fit
      to the data, with the total direct and indirect effects accounting for 90% of the
      variance. Intention was the only direct predictor of behavior. Instrumental
      attitude, affective attitude and self-efficacy had indirect effects. Although
      health interventions could usefully target these cognitive antecedents,
      simulation analyses, modeling the effects of cognition change on behavior, showed
      that only large-sized (0.8 SD) changes to affective attitude, or moderate-sized
      changes to all of these cognitions in combination were sufficient to reduce binge
      drinking.

PMID- 21945011
TI  - Social-environmental factors related to prenatal smoking.
AB  - INTRODUCTION: Cigarette smoking during pregnancy is a significant public health
      issue that has profound effects on maternal and fetal health. Although many women
      stop smoking upon pregnancy recognition, a large number continue. Given the
      higher burden of smoking among low-income women, the focus of this study is to
      examine the impact of pre-conception social-environmental influences on smoking
      cessation during the first trimester of pregnancy. METHODS: Pregnant women who
      presented for prenatal were asked to complete a screening form at their first
      prenatal appointment. Women who agreed to participate were scheduled for a total
      of four interviews; a prenatal interview at the end of each trimester and a
      postnatal interview at 2 months of infant age. The sample for the current report
      consisted of pregnant women (first trimester) with a partner (N=316). RESULTS:
      After controlling for pre-conception heaviness of smoking, a number of social
      environmental factors were associated with smoking during the first trimester.
      Women were more likely to smoke during the first trimester if their partner was a
      smoker; however, the presence of other household smokers was not associated with
      increased risk for smoking. Additionally, women with a greater proportion of
      friends (but not relatives) who smoked and more frequent exposure to
      environmental tobacco were more likely to smoke. CONCLUSIONS: This work found
      differential impacts of the social network on smoking suggesting that
      understanding relationship type, not simply number of smokers, may be important
      for smoking cessation efforts. Understanding differences in social network
      influences on smoking can help to inform interventions.

PMID- 21945012
TI  - [Falls and osteoporotic fractures prevention units: proposed Osteoporosis, Falls
      and Fractures Group of the Spanish Society of Geriatrics and Gerontology].
AB  - Since forming the Osteoporosis, Falls and Fractures Group of the Spanish Society
      (GOCF) of Geriatrics and Gerontology (SEGG) a review was performed of the
      epidemiology of falls, along with a description of measures that have shown a
      degree of effectiveness in prevention. We also present the proposal of a common
      basic model of action in fall prevention units, mainly addressed to the
      community. Finally, a consensus model falls register is presented, common to
      community level and institutional areas, with the objective of being useful and
      easy to fill in at any care level.

PMID- 21945013
TI  - SELDI-TOF MS analysis of alkylphenol exposed Atlantic cod with phenotypic
      variation in gonadosomatic index.
AB  - Proteomics is a new and promising approach to evaluate potential effects of
      pollution. In order to investigate if there is a direct link between the protein
      expression profiles obtained by the SELDI-TOF MS technology and effects observed
      at the organism level in fish, plasma samples from unexposed and 20 ppb
      alkylphenol exposed female Atlantic cod (Gadus morhua) with high phenotypic
      variation in gonadosomatic index (GSI) were analyzed by SELDI-TOF MS. Principle
      component analysis (PCA) showed that the major proteomic variation present in the
      dataset (i.e. 23.6%) could be significantly correlated to the individual
      variation in GSI, which indicates that SELDI-TOF MS data can reflect effects
      observed at higher levels of organization in fish. Further exploration of the
      other principal components revealed an additional proteomic pattern specific for
      the alkylphenol exposed females. Hence, this study supports the usefulness of
      SELDI-TOF MS as a proteomic tool in ecotoxicological research.

PMID- 21945014
TI  - Sorption behavior of nonylphenol on marine sediments: effect of temperature,
      medium, sediment organic carbon and surfactant.
AB  - The sorption behavior of nonylphenol (NP, a toxic endocrine disruptor) on marine
      sediments was studied in detail through a series of kinetic and thermodynamic
      sorption experiments. The results showed that the sorption reaction of NP on
      marine sediments reached equilibrium in 1.5 h and that it accorded well with the
      non-linear Ho-McKay pseudo-second-order model. The sorption isotherms of NP on
      H2O-treated sediments could be well described by the Linear isotherm model, while
      the sorption isotherm on H2O2-treated sediments could be well fitted with the
      Freundlich isotherm model. A positive correlation was found between the
      distribution coefficient (Kd) and the sediment organic carbon contents. The
      medium salinity showed a positive relation with the Kd and a negative relation
      with the dissolved organic carbon (DOC). Hexadecyl trimethyl ammonium bromide
      (CTAB) enhanced the sorption amount of NP the most, while sodium
      dodecylbenzenesulfonate (SDBS) enhanced it the least. The sorption reaction of NP
      on marine sediments was a spontaneous, physical, exothermic and entropy
      decreasing process.

PMID- 21945015
TI  - Pore water transport of enterococci out of beach sediments.
AB  - Enterococci are used to evaluate the safety of beach waters and studies have
      identified beach sands as a source of these bacteria. In order to study and
      quantify the release of microbes from beach sediments, flow column systems were
      built to evaluate flow of pore water out of beach sediments. Results show a peak
      in enterococci (average of 10% of the total microbes in core) released from the
      sand core within one pore water volume followed by a marked decline to below
      detection. These results indicate that few enterococci are easily removed and
      that factors other than simple pore water flow control the release of the
      majority of enterococci within beach sediments. A significantly larger quantity
      and release of enterococci were observed in cores collected after a significant
      rain event suggesting the influx of fresh water can alter the release pattern as
      compared to cores with no antecedent rainfall.

PMID- 21945016
TI  - C-(4-[18F]fluorophenyl)-N-phenyl nitrone: A novel 18F-labeled building block for
      metal free [3+2]cycloaddition.
AB  - Radiofluorination via [3+2]-nitrone-alkene cycloaddition was studied using the
      model reaction between (18)F-labeled C-(4-fluorophenyl)-N-phenyl nitrone
      ([(18)F]1) and substituted maleimides 2a-c. [(18)F]1 was prepared in RCY of
      73.6+/-5.8% and radiochemical purity of >95%. Cycloaddition of [(18)F]1 to 2a in
      toluene at 80 degrees C and in EtOH at 110 degrees C gave the respective
      isoxazolidine [(18)F]5a in >80% RCY at 10min reaction time. Reaction between
      [(18)F]1 and 2b, c also went smoothly to afford the respective cycloaddition
      products in high radiochemical yields.

PMID- 21945017
TI  - Application of digital image processing for the generation of voxels phantoms for
      Monte Carlo simulation.
AB  - This paper presents the application of a computational methodology for optimizing
      the conversion of medical tomographic images in voxel anthropomorphic models for
      simulation of radiation transport using the MCNP code. A computational system was
      developed for digital image processing that compresses the information from the
      DICOM medical image before it is converted to the Scan2MCNP software input file
      for optimization of the image data. In order to validate the computational
      methodology, a radiosurgery treatment simulation was performed using the Alderson
      Rando phantom and the acquisition of DICOM images was performed. The simulation
      results were compared with data obtained with the BrainLab planning system. The
      comparison showed good agreement for three orthogonal treatment beams of (60)Co
      gamma radiation. The percentage differences were 3.07%, 0.77% and 6.15% for
      axial, coronal and sagital projections, respectively.

PMID- 21945018
TI  - Rapid LC-MS screening for IgG Fc modifications and allelic variants in blood.
AB  - A new method for simultaneously screening allelic variants and certain Fc
      modifications on endogenous human IgG1 and IgG2 directly from blood samples is
      described. The IdeS endoproteinase was used to cleave IgG in serum to generate
      Fc, which, after denaturation, was analyzed directly as monomeric Fc (Fc/2) by LC
      MS to identify the haplotype(s) present in each individual. The relative levels
      of IgG isotype and haplotype ratios were generated along with the profile of the
      major Fc glycans and several other modifications associated with each IgG1 or
      IgG2 haplotype. Since only minute quantities (5 MUL) of blood are required and
      analysis can be highly automated, this approach lends itself to screening large
      populations. We demonstrate its utility in examining possible correlations
      between Fc properties and allelic variants. IgG1 core fucosylation, which
      significantly impacts antibody dependent cellular cytotoxicity (ADCC), showed an
      asymmetric distribution, with a small number of individuals showing unexpectedly
      high core afucosylation levels. In these individuals, IgG2 afucosylation levels
      were normal. Finally, a new IgG1 allotype, previously not characterized, was
      identified using this analytical methodology.

PMID- 21945020
TI  - Differences in endocytosis mediated by FcgammaRIIA and FcgammaRIIB2.
AB  - An important function of Fcgamma receptors is the removal of IgG-containing
      immune complexes from the circulation. The activating receptor FcgammaRIIA and
      inhibitory receptor FcgammaRIIB2 are both expressed on human myeloid cells, and
      are both capable of mediating endocytosis of immune complexes. We studied
      endocytosis of these two receptors expressed by transfection in ts20 Chinese
      hamster fibroblasts. We find that while FcgammaRIIA-mediated endocytosis requires
      the participation of the ubiquitin-conjugating system, the endocytosis of
      FcgammaRIIB2 does not. Little if any ubiquitylation of FcgammaRIIB2 was observed
      in response to immune complex binding. FcgammaRIIB2 mediates internalization of
      immune complexes at a faster rate than FcgammaRIIA, and facilitates the
      endocytosis of FcgammaRIIA upon co-engagement of both receptors. This may
      represent a novel mechanism by which the inhibitory receptor can reduce
      signalling from the activating Fcgamma receptor.

PMID- 21945019
TI  - Interaction between the immunoglobulin heavy chain 3' regulatory region and the
      IgH transcription unit during B cell differentiation.
AB  - The immunoglobulin heavy (Igh) chain locus is subject to precisely regulated
      processes, such as variable region gene formation through recombination of
      variable (V(H)), diversity (D(H)), and joining (J(H)) segments, class switching
      and somatic hypermutation. The 3' regulatory region (3' RR) is a key regulator of
      the Igh locus, and, as revealed by deletions in mouse plasma cell lines and mice,
      is required for IgH expression as well as class switching. One of the mechanisms
      by which the 3' RR regulates its targets is through long-range physical
      interactions. Such interactions between elements of the 3' RR and a target site
      in the IgH transcription unit have been detected in plasma cells, and in resting
      and switching B cells, where they have been associated with IgH expression and
      class switching, respectively. Here, we report that lentiviral shRNA knockdown of
      transcription factors, CTCF, Oct-2, or OBF-1/OCA-B, had no discernible defects in
      loop formation or H chain expression in plasma cells. J(H)-3' RR interactions in
      pre-B cell lines were specifically associated with IgH expression. J(H)-3' RR
      interactions were not detected in either Pax5-deficient or RAG-deficient pro-B
      cells, but were apparent in an Abelson-derived pro-B cell line. These
      observations imply that the 3' RR has different loop interactions with target Igh
      sequences at different stages of B cell development and Igh regulation.

PMID- 21945021
TI  - Anisotropic bone remodeling of a biomimetic metal-on-metal hip resurfacing
      implant.
AB  - Hip resurfacing (HR) is a highly attractive option for young and active patients.
      Some surgeons have advocated cementing the metaphyseal stem of the femoral
      component to improve fixation and survivorship of HR. However, extending
      component fixation to the metaphysis may promote femoral head strain shielding,
      which in turn may reduce survival of the femoral component. Replacing the
      metallic metaphyseal stem by a composite material with bone-matching properties
      could help to alleviate this phenomenon. This study uses finite element analysis
      to examine the strain state in the femoral head for three types of implant
      fixation: an unfixed metallic stem, an osseointegrated biomimetic stem and a
      cemented metallic stem. Bone remodeling is also simulated to evaluate long-term
      bone resorption due to strain shielding. Results show that the unfixed stem
      causes strain shielding in the femoral head, and that cementing the stem
      increases strain shielding. The biomimetic stem does not eliminate the strain
      shielding effect, but reduces it significantly versus the metallic cemented
      version. The current finite element study suggests that an osseointegrated
      metaphyseal stem made of biomimetic material in hip resurfacing implants could
      become an interesting alternative when fixation extension is desired.

PMID- 21945022
TI  - Levels of lipid peroxidation and antioxidant vitamins in plasma and erythrocytes
      of patients with ankylosing spondylitis.
AB  - OBJECTIVES: The aim of this study was to investigate plasma and erythrocytes
      antioxidant vitamins and lipid peroxidation (LP) levels in patients with
      ankylosing spondylitis (AS) and controls. METHODS: The study was performed on the
      blood of 13 AS patients and 13 controls. Plasma and erythrocyte samples were
      obtained from blood of the patients and controls. RESULTS: Erythrocyte
      sedimentation ratio, C-reactive protein level, Bath AS disease activity index and
      bath AS functional index were higher in patients with AS than in controls.
      Vitamins A, C, E and beta-carotene concentrations in plasma, reduced glutathione
      (GSH) and glutathione peroxidase values in erythrocyte were lower in patients
      with AS than in controls. LP concentrations were higher in the plasma and
      erythrocyte of the patients than in controls. CONCLUSION: These results provide
      some evidence for a potential role of increased lipid peroxidation and decreased
      antioxidant vitamins in ankylosing spondylitis.

PMID- 21945023
TI  - Correction of an unexpected increasing trend in glucose measurements during 7
      years recruitment to a cohort study.
AB  - OBJECTIVES: To study an unexpected, significant increase in glucose measurements
      during 7 year recruitment to a cohort study. DESIGN AND METHODS: Measurements of
      quality control solutions and blood glucose in pregnant women were done by Accu
      Chek Sensor glucometer. Time-trends were analysed by regression models and
      control charts. RESULTS: Cohort measurements were de-trended by weighted linear
      regressions based on independent control values. CONCLUSIONS: Biologically
      implausible trends in data can be corrected by using independent control values.

PMID- 21945024
TI  - Hypermethylated DNA as potential biomarkers for gastric cancer diagnosis.
AB  - OBJECTIVES: To demonstrate the diagnostic significance of methylation, an
      important molecular event in gastric carcinogenesis. DESIGN AND METHODS: We used
      methylation microarray to determine candidate genes, and performed MSP to
      evaluate the methylation status of them in tissues and sera. The effect of
      demethylation on mRNA expression was investigated by rt-PCR after gastric cancer
      cell lines were treated with 5-Aza-dC for 96 h. RESULTS: In tissues and sera of
      gastric cancer patients, a higher prevalence of methylation was observed for
      BX141696, WT1, CYP26B1, and KCNA4, compared to healthy people (p<0.05,
      respectively). Detection of the methylation prevalence of KCNA4 and CYP26B1
      together in serum demonstrated the good sensitivity (91.3%) and specificity
      (92.1%). After 5-Aza-dC treatment in gastric cancer cell lines, the mRNA
      expression level of these genes was restored. CONCLUSIONS: This study underscores
      the potential application of measurement of serum DNA methylation of these genes,
      as promising tool for gastric cancer detection.

PMID- 21945025
TI  - Interleukin-21 in hemodialyzed patients: association with the etiology of chronic
      kidney disease and the seropositivity against hepatitis C virus infection.
AB  - OBJECTIVES: IL-21 is a new pleiotropic cytokine involved in immune system
      regulation. DESIGN AND METHODS: We determined IL-21 in the plasma of hemodialyzed
      (HD) patients and healthy controls, and we tried to identify the factors which
      could affect its levels. RESULTS: Detectable levels of IL-21 were observed in the
      similar percent of HD patients and controls, but its concentration was twice
      lower in HD patients. The patients with detectable IL-21 had lower inflammatory
      state, reflected by IL-6 and TNF-alpha, compared to those with undetectable IL
      21. The association was between IL-21 and the presence of glomerulonephritis
      (p<0.05), anti-HCV seropositivity (p<0.001) and the markers of liver function.
      CONCLUSIONS: IL-21 is decreased in HD patients and is not affected by gender,
      age, inflammation, the vintage of HD, type of medication and type of used
      dialysis membrane. The etiology of chronic kidney disease and anti-HCV
      seropositivity independently affect its plasma levels in these patients.

PMID- 21945026
TI  - Study on the role of environmental parameters and HIF-1A gene polymorphism in
      coronary collateral formation among patients with ischemic heart disease.
AB  - OBJECTIVES: To evaluate the association between collateral formation and some
      environmental factors along with a polymorphism in HIF-1A gene in selected
      Iranian patients with CAD. DESIGN AND METHODS: Patients with >= 70% narrowing in
      at least one coronary vessel according to coronary angiography were enrolled. The
      patients' demographic, clinical and biochemical data were collected. The presence
      of C1772T polymorphisms within HIF-1A was analyzed using the polymerase chain
      reaction-based restriction fragment length polymorphism (PCR-RFLP). RESULTS:
      There is no significant difference between the patients with and without
      collaterals according to the frequency of T allele or HIF-1A variants. The higher
      severity of coronary vessel obstruction was positive predictor of collateral
      formation (OR=1.026, 95%, CI: 1.02-0.04, p<0.001), whereas aging and cigarette
      smoking were negative predictors (OR=0.95, 95% CI: 0.91-0.99, p<0.05; OR=0.30,
      95% CI: 0.11-0.79, p <0.05; respectively). CONCLUSIONS: The findings indicate not
      any significant association between collateral formation and polymorphic variants
      of HIF-1A and P582S substitution does not appear to influence the collateral
      formation in patients with myocardial ischemia.

PMID- 21945027
TI  - Biochemical and biomedical aspects of metabolic imidazoles.
AB  - The imidazole structure is involved in the formation of several compounds in the
      human metabolism including methyl imidazole, imidazole acetic acid, histidine,
      histamine, carnosine and homocarnosine. A number of these compounds are widely
      distributed metabolites such as histamine which is present in basophil and mast
      cells as well as being present in muscle and brain cells. This work advances
      detailed proposals on the metabolic chemical reactions which produce and
      decompose the compounds. The activity of these compounds in detrimental allergic
      medical conditions is discussed and the origin of the medical observations of the
      imidazole based medical compound known as cimetidine is discussed.

PMID- 21945028
TI  - Carbonyl group serum levels are associated with CD38 expression in patients with
      B chronic lymphocytic leukemia.
AB  - OBJECTIVES: To evaluate carbonyl groups (CG) serum levels in B-chronic
      lymphocytic leukemia (B-CLL) patients. DESIGN AND METHODS: CG serum levels were
      assessed in 48 B-CLL patients and in 30 control subjects. RESULTS: CG were
      increased in B-CLL patients. We found a positive correlation between CG with CD38
      expression and a negative correlation with ZAP 70 expression. CONCLUSIONS: B-CLL
      patients displayed an unbalance of the oxidative stress. CG serum levels could be
      considered as a prognostic factor in B-CLL.

PMID- 21945029
TI  - Which data should be used to define the role of the colonic stent in the
      management of acute, left-side, malignant colonic obstruction?

PMID- 21945030
TI  - Amplification of the G allele at SNP rs6983267 in 8q24 amplicons in myeloid
      malignancies as cause of the lack of MYC overexpression?

PMID- 21945031
TI  - Intercellular adhesion molecule, plasma adiponectin and albuminuria in type 2
      diabetic patients.
AB  - AIMS: Our study addressed the influence of early inflammatory stages of diabetic
      kidney disease: leukocyte adhesion and monocyte activation (as assessed by
      intercellular leukocyte adhesion molecule-ICAM-1 and monocyte chemoatractant
      protein-MCP-1) on the degree of albuminuria. Plasma levels of adiponectin, a
      possible anti-inflammatory counteracting mechanism, were also studied in
      correlation to the above-mentioned cytokines. METHODS: 79 consecutive type 2
      diabetic outpatients and 46 controls were included. Routine laboratory analysis,
      urinary albumin to creatinine ratio (uACR), plasma adiponectin, plasma ICAM-1 and
      urinary MPC-1 were assessed. RESULTS: In multiple regression ICAM-1 (p=0.004) and
      adiponectin (p=0.04) were the main determinants of uACR. Plasma adiponectin
      positively correlated to ICAM-1 (p=0.03, r=0.24). In albuminuric patients (uACR
      >=30 mg/g) plasma adiponectin was significantly higher compared to
      normoalbuminuric ones (uACR <30 mg/g). In albuminuric patients the main
      determinants of uACR were plasma ICAM-1 and adiponectin. In multiple regression
      ICAM-1 is the only one that retains statistical significance (p=0.02). Urinary
      MCP-1 did not correlate to uACR. CONCLUSIONS: In our type 2 diabetic patients,
      plasma levels of ICAM-1 and adiponectin are predictive for albuminuria. Urinary
      MCP-1 does not correlated to uACR. Plasma adiponectin positively correlates to
      adhesion molecule ICAM-1 in our cohort.

PMID- 21945032
TI  - Gait adaptation during obstacle crossing reveals impairments in the visual
      control of locomotion in Williams syndrome.
AB  - Recent evidence indicates that individuals with Williams syndrome (WS), a rare
      genetically based neurodevelopmental disorder, show abnormalities of parietal and
      cerebellar regions of the brain that may be involved in the visual control of
      locomotion. Here we examined whether parietal and cerebellar abnormalities
      contribute to deficits in spatiotemporal characteristics and foot placement
      variability during obstacle crossing in adults with WS, when compared with an IQ
      matched group of adults with Down syndrome (DS) and typically developing adult
      controls. We used the GAITRite walkway to examine the spatiotemporal
      characteristics and foot placement variability relative to a small ground-based
      obstacle in the travel path. We found that adults with WS showed late adjustments
      to spatiotemporal gait characteristics alongside an exaggerated and more
      spatially constrained visual guidance of foot positioning in the final steps
      prior to stepping over the obstacle. In contrast, the adults with DS showed
      longer step duration and more variable step length and step duration during the
      crossing and recovery steps after the obstacle, suggestive of cerebellar
      dysfunction. Although the controls were able to reduce the variability of foot
      placement across the obstacle crossing trials, both the WS and DS groups did not
      become more consistent with practice. These findings indicate a less flexible and
      overly constrained visuomotor system in WS, which is consistent with more
      widespread and diffuse abnormalities in parietal and cerebellar regions.

PMID- 21945034
TI  - Positive correlation between elevated plasma cholesterol levels and cognitive
      impairments in LDL receptor knockout mice: relevance of cortico-cerebral
      mitochondrial dysfunction and oxidative stress.
AB  - Convergent epidemiological, clinical, and experimental findings indicate that
      hypercholesterolemia contributes to the onset of Alzheimer's disease (AD)-like
      dementia, but the exact underlying mechanisms remains unknown. In this study, we
      evaluated the cognitive performance of mice submitted to a model of
      hypercholesterolemia, as well as its relationship with mitochondrial dysfunction
      and oxidative stress, two key events involved in AD pathogenesis. Wild-type
      C57bl/6 or low density lipoprotein receptor (LDLr)-deficient mice were fed with
      either standard or cholesterol-enriched diet for a 4-week period and tested for
      spatial learning and memory in the object location task. LDLr-/- mice displayed
      spatial learning and memory impairments regardless of diet. Moreover, LDLr-/-
      mice fed cholesterol-enriched diet presented a significant decrease in the
      mitochondrial complexes I and II activities in the cerebral cortex, which were
      negatively correlated with respective blood cholesterol levels. Additionally,
      hypercholesterolemic LDLr-/- mice presented a significant decrease in glutathione
      levels, about 40% increase in the thiobarbituric acid-reactive substances levels,
      as well as an imbalance between the peroxide-removing-related enzymes glutathione
      peroxidase/glutathione reductase activities in the cerebral cortex. These
      findings indicate a significant relationship between hypercholesterolemia,
      cognitive impairment, and cortico-cerebral mitochondrial dysfunctional/oxidative
      stress. Because of the involvement of such alterations in AD patients, our data
      render this mouse model of hypercholesterolemia a useful approach to comprehend
      the molecular events mediating AD pathogenesis.

PMID- 21945035
TI  - Sex-dimorphic effects of dehydroepiandrosterone in diabetic neuropathy.
AB  - Our recent observations have demonstrated that gonadectomy in female, but not in
      male diabetic animals, exert protection in the peripheral nervous system and that
      these effects were associated with an increase in the levels of
      dehydroepiandrosterone (DHEA) in the female sciatic nerve [Pesaresi M, Giatti S,
      Cavaletti G, Abbiati F, Calabrese D, Bianchi R, Caruso D, Garcia-Segura LM,
      Melcangi RC (2011) Exp Neurol 228:215-221]. That is interesting because the
      neuroprotective effects of this neuroactive steroid have so far only been
      analyzed in male diabetic animals. Using the experimental model of streptozotocin
      induced diabetic neuropathy, we have here compared the effect of DHEA treatment
      in male and in female animals. Data obtained indicate that DHEA treatment is able
      to counteract the decrease in nerve conduction velocity (NCV) induced by diabetes
      in both sexes. However, it was only in females that this neuroactive steroid was
      able to reestablish NCV to control levels. In addition, it was only in females
      that DHEA exerted neuroprotective actions on functional (i.e., thermal
      sensitivity) or molecular parameters, such as gene expression of myelin proteins.
      Sex-depending neuroprotective effects of DHEA were also confirmed by the finding
      that it was only in females that this neuroactive steroid fully restored the
      intra-epidermal nerve fiber density, which was decreased by diabetes.
      Interestingly, the metabolic fate of DHEA is also different in males and females.
      Thus, analysis of the neuroactive steroid levels after the treatment with DHEA
      indicates that in the sciatic nerve of male diabetic animals 17alpha-estradiol
      levels decrease in association with an increase of its isomer 17beta-estradiol
      and with a decrease in the levels of alpha-androstane-3alpha, 17beta-diol. These
      changes were not observed in the sciatic nerve of females. Altogether, these
      results suggest that DHEA could be considered as a candidate for a sex-specific
      therapy based on neuroactive steroids.

PMID- 21945033
TI  - The coumarin scopoletin potentiates acetylcholine release from synaptosomes,
      amplifies hippocampal long-term potentiation and ameliorates anticholinergic- and
      age-impaired memory.
AB  - In a previous study the simple, naturally derived coumarin scopoletin (SCT) was
      identified as an inhibitor of acetylcholinesterase (AChE), using a pharmacophore
      based virtual screening approach. In this study the potential of SCT as
      procholinergic and cognition-enhancing therapeutic was investigated in a more
      detailed way, using different experimental approaches like measuring newly
      synthesized acetylcholine (ACh) in synaptosomes, long-term potentiation (LTP)
      experiments in hippocampal slices, and behavior studies. SCT enhanced the K+
      stimulated release of ACh from rat frontal cortex synaptosomes, showing a bell
      shaped dose effect curve (E(max): 4 MUM). This effect was blocked by the
      nicotinic ACh receptor (nAChR) antagonists mecamylamine (MEC) and dihydro-beta
      erythroidine (DHE). The nAChR agonist (and AChE inhibitor) galantamine induced a
      similar increase in ACh release (E(max): 1 MUM). SCT potentiated LTP in
      hippocampal slices of rat brain. The high-frequency stimulation (HFS)-induced, N
      methyl-D-aspartate (NMDA) receptor dependent LTP of field excitatory postsynaptic
      potentials at CA3-CA1 synapses was greatly enhanced by pre-HFS application of SCT
      (4 MUM for 4 min). This effect was mimicked by nicotine (2 MUM) and abolished by
      MEC, suggesting an effect on nAChRs. SCT did not restore the total inhibition of
      LTP by NMDA receptor antagonist D, L-2-amino-5-phosphonopentanoic acid (AP-5).
      SCT (2 MUg, i.c.v.) increased T-maze alternation and ameliorated novel object
      recognition of mice with scopolamine-induced cholinergic deficit. It also reduced
      age-associated deficits in object memory of 15-18-month-old mice (2 mg/kg sc).
      Our findings suggest that SCT possesses memory-improving properties, which are
      based on its direct nAChR agonistic activity. Therefore, SCT might be able to
      rescue impaired cholinergic functions by enhancing nAChR-mediated release of
      neurotransmitters and promoting neural plasticity in hippocampus.

PMID- 21945036
TI  - Replication of Lettuce chlorosis virus (LCV), a crinivirus in the family
      Closteroviridae, is accompanied by the production of LCV RNA 1-derived novel
      RNAs.
AB  - Cloned infectious complementary DNAs of the bipartite genomic RNAs of Lettuce
      chlorosis virus (LCV) were constructed. Inoculation of tobacco protoplasts with
      the in vitro produced RNAs 1 and 2 transcripts, or with RNA 1 transcript alone,
      resulted in viral replication accompanied by the production of novel LCV RNA 1
      derived RNAs. They included the abundantly accumulating LM-LCVR1-1 (~0.38 kb) and
      LM-LCVR1-2 (~0.3 kb), and the lowly accumulating HM-LCVR1-1 (~8.0 kb) and HM
      LCVR1-2 (~6.6 kb), all of which reacted with riboprobes specific to the 5' end of
      RNA 1 in Northern blot analysis. LM-LCVR1-1 and HM-LCVR1-2 accumulated as
      positive-stranded RNAs that lacked complementary negative strands, while HM-LCVR1
      1 and LM-LCVR1-2 accumulated in both polarities. Additional Northern blot,
      reverse transcription-polymerase chain reaction, cloning, and sequence analyses
      revealed LM-LCVR1-2 to be an authentic RNA 1-derived defective (D)RNA, suggesting
      that its synthesis and maintenance are supported in trans by an RNA 1 encoded
      replication machinery.

PMID- 21945039
TI  - Glycobiology: the study of the sweet life.

PMID- 21945037
TI  - The interactive effect of change in perceived stress and trait anxiety on vagal
      recovery from cognitive challenge.
AB  - The present study tested the hypothesis that the change in state negative affect
      (measured as perceived stress) after cognitive challenge moderates the
      relationship of trait anxiety and anger to vagal recovery from that challenge.
      Cardiac vagal control (assessed using heart rate variability) and respiratory
      rate were measured in a sample of 905 participants from the Midlife in the United
      States Study. Cognitive challenges consisted of computerized mental arithmetic
      and Stroop color-word matching tasks. Multiple regression analyses controlling
      for the effects of the demographic, lifestyle, and medical factors influencing
      cardiac vagal control showed a significant moderating effect of change in
      perceived stress on the relationship of trait anxiety to vagal recovery from
      cognitive challenges (Beta=.253, p=.013). After adjustment for respiratory rate,
      this effect became marginally significant (Beta=.177, p=.037). In contrast, for
      the relationship of trait anger to vagal recovery, this effect was not
      significant either before (Beta=.141, p=.257) or after (Beta=.186, p=.072)
      adjusting for respiratory rate. Secondary analyses revealed that among the
      individuals with higher levels of trait anxiety, greater reductions in perceived
      stress were associated with greater increases in cardiac vagal control after the
      challenge. In contrast, among the individuals with lower levels of trait anxiety,
      changes in perceived stress had no impact on vagal recovery. Therefore, change in
      perceived stress moderates the relationship of trait anxiety, but not trait
      anger, to vagal recovery from cognitive challenge.

PMID- 21945038
TI  - Mammalian O-mannosylation: unsolved questions of structure/function.
AB  - Post-translational modification of polypeptides with glycans increases the
      diversity of the structures of proteins and imparts increased functional
      diversity. Here, we review the current literature on a relatively new O
      glycosylation pathway, the mammalian O-mannosylation pathway. The importance of O
      mannosylation is illustrated by the fact that O-mannose glycan structures play
      roles in a variety of processes including viral entry into cells, metastasis,
      cell adhesion, and neuronal development. Furthermore, mutations in the enzymes of
      this pathway are causal for a variety of congenital muscular dystrophies. Here we
      highlight the protein substrates, glycan structures, and enzymes involved in O
      mannosylation as well as our gaps in understanding structure/function
      relationships in this biosynthetic pathway.

PMID- 21945040
TI  - Achieving broad molecular insights into dynamic protein interactions by
      integrated structural-kinetic approaches.
AB  - A network of dynamic protein interactions with their protein partners,
      substrates, and ligands is known to be crucial for biological function. Revealing
      molecular and structural-based mechanisms at atomic resolution and in real-time
      is fundamental for achieving a basic understanding of cellular processes. These
      technically challenging goals may be achieved by combining time-resolved
      spectroscopic and structural-kinetic tools, thus providing broad insights into
      specific molecular events over a wide range of timescales. Here we review
      representative studies utilizing such an integrated real-time structural approach
      designed to reveal molecular mechanisms underlying protein interactions at atomic
      resolution.

PMID- 21945042
TI  - Camelpox: target for eradication?

PMID- 21945043
TI  - Learning slow features with reservoir computing for biologically-inspired robot
      localization.
AB  - This work proposes a hierarchical biologically-inspired architecture for learning
      sensor-based spatial representations of a robot environment in an unsupervised
      way. The first layer is comprised of a fixed randomly generated recurrent neural
      network, the reservoir, which projects the input into a high-dimensional, dynamic
      space. The second layer learns instantaneous slowly-varying signals from the
      reservoir states using Slow Feature Analysis (SFA), whereas the third layer
      learns a sparse coding on the SFA layer using Independent Component Analysis
      (ICA). While the SFA layer generates non-localized activations in space, the ICA
      layer presents high place selectivity, forming a localized spatial activation,
      characteristic of place cells found in the hippocampus area of the rodent's
      brain. We show that, using a limited number of noisy short-range distance sensors
      as input, the proposed system learns a spatial representation of the environment
      which can be used to predict the actual location of simulated and real robots,
      without the use of odometry. The results confirm that the reservoir layer is
      essential for learning spatial representations from low-dimensional input such as
      distance sensors. The main reason is that the reservoir state reflects the recent
      history of the input stream. Thus, this fading memory is essential for detecting
      locations, mainly when locations are ambiguous and characterized by similar
      sensor readings.

PMID- 21945041
TI  - FimH, a TLR4 ligand, induces innate antiviral responses in the lung leading to
      protection against lethal influenza infection in mice.
AB  - Fimbriae H protein (FimH) is a novel TLR4 ligand that has been shown to stimulate
      the innate immune system and elicits protective responses against bacterial and
      viral infections. Here, we evaluated the protective role of local delivery of
      FimH against influenza A infection in a mouse model. We show that intranasal
      delivery of FimH prior to lethal challenge with influenza A virus, resulted in
      decreased morbidity and mortality in wild-type, but not TLR4(-/-), mice.
      Importantly, FimH was able to reduce the early viral burden in the lung leading
      to minimal cell infiltration into the airway lumen and reduced pulmonary
      pathology following infection in wild type mice compared to TLR4(-/-) mice. Local
      delivery of FimH to C57BL/6, not TLR4(-/-), mice in a prophylactic manner
      increased the IL-12 and RANTES responses as well as neutrophil recruitment into
      the airway lumen. These effects correlate to the course of influenza infection.
      The FimH-mediated antiviral response against influenza virus appears to be
      partially dependent on alveolar macrophages. The antiviral effects are likely
      mediated by the innate mediators (TNF-alpha, IL-12 or RANTES) and/or by
      activation of a feedback inhibition loop to curtail the pulmonary inflammation
      possibly be the potential mechanisms involved in FimH-mediated protection. FimH
      thus holds promise to be a possible prophylactic mean of control against
      influenza viral infection.

PMID- 21945044
TI  - Scorpion venom (Odontobuthus doriae) induces apoptosis by depolarization of
      mitochondria and reduces S-phase population in human breast cancer cells (MCF-7).
AB  - Venom of some species of scorpions induces apoptosis and arrests proliferation in
      cancer cells. This is an important property that can be harnessed and can lead to
      isolation of compounds of therapeutic importance in cancer research. Cytotoxicity
      was investigated using MTT reduction and confirmed with lactate dehydrogenase
      release following venom exposure. Apoptosis was evaluated with determination of
      mitochondrial membrane potential, reactive nitrogen species assay, measurement of
      Caspase-3 activity and DNA fragmentation analysis. To confirm that venom can
      inhibit DNA synthesis in proliferating breast cancer cells, immunocytochemical
      detection of BrdU incorporation was done. Our results demonstrated that venom of
      Odontobuthus doriae not only induced apoptosis but lead to the inhibition of DNA
      synthesis in human breast cancer cells (MCF-7). Cell viability decreased with
      parallel increment of LDH release in dose dependent manner after treatment with
      varying concentrations of venom. Moreover, venom depleted cellular antioxidants
      evidenced by depression of GSH and Catalases and concomitantly increased reactive
      nitrogen intermediates (RNI). These events were related to the depolarization of
      mitochondria and associated Caspase-3 activation following venom treatment in a
      concentration dependent manner. Finally, fragmentation of nuclear DNA following
      venom treatment confirmed the apoptotic property of the said venom. These results
      suggest that venom of O. doriae can be potential source for the isolation of
      effective anti-proliferative and apoptotic molecules.

PMID- 21945045
TI  - Toxic effects following phosgene exposure of human epithelial lung cells in vitro
      using a CULTEX(r) system.
AB  - The aim of the present study was to investigate toxic effects following phosgene
      exposure of human epithelial lung cells (A549) in vitro using a CULTEX(r) system.
      In particular, toxic effects regarding early biomarkers emerging during the
      latency period following exposure might be of great value for medical treatment.
      Cells cultured on semi-permeable membranes were directly exposed at the liquid
      air interface to different concentrations of phosgene, or dry medical air. Cell
      membrane integrity (leakage of LDH), metabolic activity (reduction of Alamar
      Blue), oxidative damage (GSH, and HO-1, in cell lysates), and release of IL-8,
      were studied. For most of the above-mentioned biological end-point markers,
      significant changes could be assessed following a 20 min exposure to 1.0 ppm and
      2.0 ppm phosgene. Moreover, except for IL-8, all biological marker profiles
      showed to be in line with results obtained by others in animal studies. The C*t
      value of 40 ppm min appeared to be constant. The overall results suggest that at
      4 h post-exposure a maximal level of toxicity was achieved. Our results
      demonstrate the suitability of a CULTEX(r) system to detect toxic effects induced
      by phosgene on human epithelial lung cells, which may contribute to the discovery
      of early biomarkers for new medical countermeasures.

PMID- 21945046
TI  - Study of embryotoxicity of Fusarium mycotoxin butenolide using a whole rat embryo
      culture model.
AB  - Butenolide, a mycotoxin elaborated by several toxigenic Fusarium species, has
      been implicated as an etiological factor of Kashin-Beck disease and it is always
      detected in food from endemic Kashin-Beck disease areas. Although butenolide is
      considered as a potential health risk to humans and animals, its toxicity targets
      and mechanism of action have not been fully understood and the knowledge of its
      developmental toxicity is absent. The present study investigated butenolide
      embryotoxicity via an in vitro whole embryo culture system using rat embryos.
      Embryos exposed to butenolide at a concentration of 0.625 mg/L showed and
      differentiation similar to that of the control embryos (=no observed adverse
      effect concentration; NOAECwec). The embryonic growth and differentiation were
      affected, represented as reduced crown-rump length and head length, and decreased
      number of somites from 1.25 mg/L. Total morphological scores decreased
      significantly at the concentration of butenolide of 2.5 mg/L. All embryos were
      malformed at 3.75 mg/L and above (=ICMaxWEC), presenting growth retardation with
      flexion failure and irregular somite differentiation. The IC503T3 of butenolide
      as calculated from the balb/c 3T3 cytotoxicity test is 6.45 mg/L. Our study shows
      that butenolide exerts detrimental effects on embryo development in vitro by
      inducing growth retardation and differentiation inhibition, and the
      embryotoxicity effect of butenolide should be treated with caution.

PMID- 21945047
TI  - Paraptosis-like cell death induced by yessotoxin.
AB  - This study shows that BC3H1 myoblast cell lines exposed to 100 nM yessotoxin
      (YTX) undergo a form of programmed cell death distinct from apoptosis and with
      features resembling paraptosis. Morphologically, cells treated with YTX reveal
      extensive cytoplasmic vacuolation, mitochondrial and endoplasmic reticulum
      swelling, uncondensed chromatin and cytoskeletal alterations. DNA electrophoresis
      evidences lack of DNA fragmentation and Western blotting analysis demonstrates
      activation of the mitogen-activated protein kinase JNK/SAPK1. Further
      characterisation of this form of programmed cell death may have interest within
      medicine and cancer therapy.

PMID- 21945048
TI  - Historical control data of neoplastic lesions in the Wistar Hannover Rat among
      eight 2-year carcinogenicity studies.
AB  - Incidences of neoplastic lesions were evaluated in untreated Hannover Wistar Rats
      RjHan: WI (470 males and 470 females) used as control animals in eight
      carcinogenicity studies. All these studies were performed in a similar
      environment either for the in vivo and the postmortem evaluation. The major
      neoplastic lesions were found in the endocrine, integumentary and reproductive
      systems. Pituitary adenoma was the most frequent neoplasm and occurred in 33.9%
      of the males and 54.6% of the female rats. The other most frequent tumors in
      males were thyroid C-cell adenoma (8.6%), pancreatic islet cell adenoma (8.1%),
      subcutaneous fibrosarcoma (6.6%), subcutaneous fibroma (4.7%), benign
      pheochromocytoma (3.4%), and cutaneous keratoacanthoma (3.4%). In females, the
      other highest incidences were mammary fibroadenoma (29%), uterine endometrial
      stromal polyp (18.1%), mammary adenocarcinoma (14.2%), mammary fibroadenoma with
      atypia (13.7%), thyroid C-cell adenoma (7.5%), benign thymoma (3.7%), and
      subcutaneous fibrosarcoma (3.6%). All these data were compared to previously
      published historical control data. This retrospective analysis was undergone in
      order to illustrate the result of a stable organization which guarantees a robust
      historical data base for neoplastic and non neoplastic findings.

PMID- 21945049
TI  - Anesthetic management of ovarian teratoma excision associated with anti-N-methyl
      D-aspartate receptor encephalitis.

PMID- 21945050
TI  - Not every subseptate uterus requires surgical correction to reduce poor
      reproductive outcome.
AB  - OBJECTIVE: To evaluate whether hysteroscopic septoplasty should be performed in
      all women diagnosed with subseptate uterus. METHODS: In a prospective study, 138
      patients diagnosed with subseptate uterus at the First Affiliated Hospital of
      Guangxi Medical University, Nanning, China, were enrolled between January 1,
      2006, and March 1, 2011, and reproductive outcomes were compared among women who
      did and those who did not undergo hysteroscopic resection. Women were divided in
      2 groups: group A comprised women with a history of recurrent spontaneous
      abortion (RSA), and was subdivided into control (A1) and surgery (A2) groups;
      group B comprised women with no history of poor reproductive outcomes, and was
      subdivided into control (B1) and surgery (B2) groups. RESULTS: The rates of
      pregnancy and term delivery were higher in group A2 than in group A1 (P<0.05).
      The incidence of RSA and preterm delivery was higher in group A1 than in group A2
      (P<0.05). There was no difference in pregnancy rate, incidence of RSA, or preterm
      or term delivery between group B1 and group B2. CONCLUSION: Hysteroscopic
      septoplasty significantly improved pregnancy outcomes in women with a history of
      RSA, but did not influence reproductive outcomes in women with no history of poor
      pregnancy outcomes.

PMID- 21945051
TI  - Wolbachia pipientis is associated with different mitochondrial haplotypes in
      natural populations of Drosophila willistoni.
AB  - The prevalence of the endosymbiont Wolbachia pipientis and its effects on
      mitochondrial genetic diversity were analyzed in natural populations of
      Drosophila willistoni, a neotropical species recently infected. Total infection
      rate was 55% and no evidence was found that the Wolbachia infection decreased the
      diversity of mtDNA. Wolbachia was seen to be associated with different
      mitochondria, suggesting multiple horizontal transmission events and/or
      transmission paternal leakage of mitochondrial and/or Wolbachia. These hypotheses
      are evaluated in the context of the present study and other research.

PMID- 21945052
TI  - Directional movement of entomopathogenic nematodes in response to electrical
      field: effects of species, magnitude of voltage, and infective juvenile age.
AB  - Entomopathogenic nematodes respond to a variety of stimuli when foraging.
      Previously, we reported a directional response to electrical fields for two
      entomopathogenic nematode species; specifically, when electrical fields were
      generated on agar plates Steinernema glaseri (a nematode that utilizes a cruiser
      type foraging strategy) moved to a higher electric potential, whereas Steinernema
      carpocapsae, an ambush-type forager, moved to a lower potential. Thus, we
      hypothesized that entomopathogenic nematode directional response to electrical
      fields varies among species, and may be related to foraging strategy. In this
      study, we tested the hypothesis by comparing directional response among seven
      additional nematode species: Heterorhabditis bacteriophora, Heterorhabditis
      georgiana, Heterorhabditis indica, Heterorhabditis megidis, Steinernema feltiae,
      Steinernema riobrave, and Steinernema siamkayai. S. carpocapsae and S. glaseri
      were also included as positive controls. Heterorhabditids tend toward cruiser
      foraging approaches whereas S. siamkayai is an ambusher and S. feltiae and S.
      riobrave are intermediate. Additionally, we determined the lowest voltage that
      would elicit a directional response (tested in S. feltiae and S. carpocapsae),
      and we investigated the impact of nematode age on response to electrical field in
      S. carpocapsae. In the experiment measuring diversity of response among species,
      we did not detect any response to electrical fields among the heterorhabditids
      except for H. georgiana, which moved to a higher electrical potential; S. glaseri
      and S. riobrave also moved to a higher potential, whereas S. carpocapsae, S.
      feltiae, and S. siamkayai moved to a lower potential. Overall our hypothesis that
      foraging strategy can predict directional response was supported (in the
      nematodes that exhibited a response). The lowest electric potential that elicited
      a response was 0.1 V, which is comparable to electrical potential associated with
      some insects and plant roots. The level of response to electrical potential
      diminished with nematode age. These results expand our knowledge of electrical
      fields as cues that may be used by entomopathogenic nematodes for host-finding or
      other aspects of navigation in the soil.

PMID- 21945053
TI  - Chemical and physical characteristics of lamb meat related to crossbreeding of
      Romanov ewes with Suffolk and Charollais sires.
AB  - The aim was to evaluate the effects of crossbreeding Romanov (RO) ewes with
      Suffolk (SF) and Charollais (CH) sires on the chemicophysical characteristics and
      FA profile of the Quadriceps femoris muscle (QFM) in lambs fattened under organic
      conditions. The experimental animals were male lamb twins of two different
      crossbreds; CH 50 RO 50 and SF 50 RO 50. Lambs were slaughtered at an average
      live weight of 31kg. CH 50 RO 50 displayed higher contents of dry matter and
      intramuscular fat of the QFM. A lower pH value of CH 50 RO 50 was reflected in an
      increase of WHC. Meat of SF 50 RO 50 lambs had more lightness (L*) and yellowness
      (b*). The CH 50 RO 50 genotype showed a significantly higher proportion of C18:3n
      3cis and n-3 PUFA than the SF 50 RO 50 genotype. The genotype also affected the
      Delta(9)-desaturase (16) index.

PMID- 21945054
TI  - The structural studies of fullerenol C60(OH)24 and nitric oxide mixture in water
      solvent - MD simulation.
AB  - The potential nitric oxide scavenging activity of polyhydroxylated derivative of
      fullerene C(60)(OH)(24), called fullerenol, has been tested using the computer
      simulation (MD) method. The study is motivated by the expected diverse biological
      applications of water-soluble fullerenols. The static structure factor of the
      nitric oxide and fullerenol mixture in water solvent, related to the neutron
      scattering experiment, has been calculated and discussed. The distribution of
      nitric oxide NO molecules near fullerenol in water solution have been observed by
      calculating the partial radial distribution function at several temperatures,
      from 300 to 325K. The slight uptake of nitric oxide molecules by fullerenol has
      been detected at physiological temperature T=310K. The temperature dependence of
      the nitric oxide scavenging by fullerenol has been estimated.

PMID- 21945055
TI  - Monte Carlo simulation of near infrared autofluorescence measurements of in vivo
      skin.
AB  - The autofluorescence properties of normal human skin in the near-infrared (NIR)
      spectral range were studied using Monte Carlo simulation. The light-tissue
      interactions including scattering, absorption and anisotropy propagation of the
      regenerated autofluorescence photons in the skin tissue were taken into account
      in the theoretical modeling. Skin was represented as a turbid seven-layered
      medium. To facilitate the simulation, ex vivo NIR autofluorescence spectra and
      images from different skin layers were measured from frozen skin vertical
      sections to define the intrinsic fluorescence properties. Monte Carlo simulation
      was then used to study how the intrinsic fluorescence spectra were distorted by
      the tissue reabsorption and scattering during in vivo measurements. We found that
      the reconstructed model skin spectra were in good agreement with the measured in
      vivo skin spectra from the same anatomical site as the ex vivo tissue sections,
      demonstrating the usefulness of this modeling. We also found that difference
      exists over the melanin fluorescent wavelength range (880-910 nm) between the
      simulated spectrum and the measured in vivo skin spectrum from a different
      anatomical site. This difference suggests that melanin contents may affect in
      vivo skin autofluorescence properties, which deserves further investigation.

PMID- 21945056
TI  - De novo design of chiral organotin cancer drug candidates: validation of
      enantiopreferential binding to molecular target DNA and 5'-GMP by UV-visible,
      fluorescence, (1)H and (31)P NMR.
AB  - N,N-bis[(R-/S-)-1-benzyl-2-ethoxyethane] tin (IV) complexes were synthesized by
      applying de novo design strategy by the condensation reaction of (R-/S-)2-amino-2
      phenylethanol and dibromoethane in presence of dimethyltin dichloride and
      thoroughly characterized by elemental analysis, conductivity measurements, IR,
      ESI-MS, (1)H, (13)C and (119)Sn, multinuclear NMR spectroscopy and XRD study.
      Enantioselective and specific binding profile of R-enantiomer 1 in comparison to
      S-enantiomer 2 with ultimate molecular target CT-DNA was validated by UV-visible,
      fluorescence, circular dichroism, (1)H and (31)P NMR techniques. This was further
      corroborated well by interaction of 1 and 2 with 5'-GMP.

PMID- 21945057
TI  - Optimizing colorectal cancer screening by getting FIT right.

PMID- 21945058
TI  - Bugs, stool, and the irritable bowel syndrome: too much is as bad as too little?

PMID- 21945059
TI  - Molecular gastronomy: how to make the critical intestinal Foxp3+ Treg cell.

PMID- 21945060
TI  - Thiopurines for inflammatory bowel disease: time to engage with dermatologists?

PMID- 21945061
TI  - Inclusion of extra perforators--a single and efficient measure to prevent
      vascular insufficiency in unreliable thoracodorsal artery perforator flaps.
AB  - BACKGROUND: The purpose of the study is to establish a clearly defined principle
      to prevent the vascular insufficiency of thoracodorsal artery perforator flaps,
      including the criteria to identify unreliable flaps and the measure to improve
      their viability. METHODS: The whole project comprised the preliminary study and
      the major study. In the preliminary study of 42 patients, the intrinsic risk
      factors associated with the vascular insufficiency of flaps were identified.
      Using colour Doppler scanning, the linear correlation between colour signal width
      and external diameter of perforators was demonstrated. Based on the findings, the
      principle to prevent vascular insufficiency of flaps was established which
      involved two steps. First was introducing the inclusion criteria to identify the
      unreliable flaps. Second was including extra perforators as the single measure to
      improve the viability of unreliable flaps. The principle was applied in the major
      study of 50 patients to prove its efficacy. RESULTS: In the major study, flap
      viability was not compromised in the 35 patients without any of the inclusion
      criteria. At least one of the inclusion criteria was met in the other 15
      patients. Three of the 15 unreliable flaps sustained vascular insufficiency. In
      one patient, only single small-sized perforator was available to support the
      flap. The principle was disobeyed in the other two patients because of the
      intertwined relation, and their less dominant perforators were cut to spare the
      intertwined motor nerves. The rate of compromised flap viability was 2.1% in the
      48 patients with complete execution of the principle in comparison with the 16.7%
      rate in the preliminary study. CONCLUSIONS: The inclusion criteria are useful to
      identify unreliable thoracodorsal artery perforator flaps. Inclusion of extra
      perforators is a single and efficient measure to prevent vascular insufficiency
      of unreliable flaps.

PMID- 21945062
TI  - The commissure-based triangular flap for lip revision following reconstruction of
      a through-and-through defect.

PMID- 21945063
TI  - Multifocal necrotising fasciitis: an overlooked entity?
AB  - OBJECTIVE: The aim of the study is to report a case of multi-focal necrotising
      fasciitis, review research on this subject to identify common aetiological
      factors and highlight suggestions to improve management. CONTEXT: Necrotising
      fasciitis is a severe, life-threatening soft tissue infection that typically
      arises from a single area, usually secondary to a minor penetrating injury. Multi
      focal necrotising fasciitis, where there is more than one non-contiguous area of
      necrosis, is much less commonly reported. There are no guidelines specific to the
      management of multi-focal necrotising fasciitis, and its under-reporting may lead
      to missed management opportunities. DESIGN: A systematic literature review in
      accordance with the Preferred Reporting Items for Systematic Reviews and Meta
      Analyses (PRISMA) protocol. DATA SOURCES: A search of MEDLINE, OLD MEDLINE and
      the Cochrane Collaboration was performed from 1966 to March 2011 using 16 search
      terms. DATA EXTRACTION: All articles were screened for genuine non-contiguous
      multi-focal necrotising fasciitis. Of the papers that met this criterion, data on
      patient demographics, likely inciting injury, presentation time-line, microbial
      agents, sites affected, objective assessment scores, treatment and outcome were
      extracted. DATA SYNTHESIS: A total of 31 studies met our inclusion criteria and
      33 individual cases of multi-focal necrotising fasciitis were included in the
      quantitative analysis. About half (52%) of cases were type II necrotising
      fasciitis; 42% of cases had identifiable inciting injuries; 21% of cases
      developed multi-focal lesions non-synchronously, of which 86% were type II.
      Nearly all (94%) of cases had incomplete objective assessment scores. One case
      identified inflammatory imaging findings prior to clinical necrosis. CONCLUSIONS:
      Multifocality in necrotising fasciitis is likely to be associated with type II
      disease. We postulate that validated objective tools will aid necrotising
      fasciitis management pathways that will identify high-risk groups for
      multifocality and advise early pre-emptive imaging. We recommend the adoption of
      regional multi-focal necrotising fasciitis registers.

PMID- 21945064
TI  - Multiple rheumatoid bursal cysts that were finally effectively treated by
      combining surgical resection and sclerotherapy.
AB  - A 71-year-old male who had been diagnosed with rheumatoid arthritis 3 years
      previously developed multiple subcutaneous cysts on his buttock, elbow, knee,
      hand and back. The diameters of the cysts were 10-15 cm. The characteristic fluid
      and pathology of the cysts led to the diagnosis of multiple rheumatoid bursal
      cyst (MRBC). The patient was keen to treat the cyst on his buttock as it hampered
      his sitting position. However, it resisted several kinds of sclerotherapies,
      including absolute alcohol, OK-432, minocycline and dexamethasone. When the cyst
      grew further, it was resected surgically; however, the cyst recurred immediately.
      It was finally brought under control by injecting it with OK-432. The thick cyst
      wall, which resisted the various sclerotherapies, was removed surgically, and a
      new capsule developed inside the cavity; adding a sclerotant to newly made thin
      capsule made us possible to treat this resistant large bursal cyst.

PMID- 21945065
TI  - Risk factors for surgical site infection in children at the teaching hospital
      Gabriel Toure, Bamako.
AB  - A six-month prospective surveillance study of postoperative surgical site
      infections (SSIs) was undertaken between January and June 2010 in paediatric
      patients aged <15 years, in the University Hospital Gabriel Toure, Mali. SSI was
      documented in 43 out of 352 children (12.2%). SSIs were significantly more common
      after emergency operations, in patients with a National Nosocomial Infection
      Surveillance System (NNISS) score of 2 or 3, and in patients operated on by
      trainee rather than by experienced surgeons. Children with anaemia or
      malnutrition were significantly more likely to develop infection postoperatively.
      Patients' sex, duration of preoperative stay and the number of patients in the
      hospital room were not considered as risk factors for infection (P>0.05).

PMID- 21945066
TI  - Use of e-learning to enhance medical students' understanding and knowledge of
      healthcare-associated infection prevention and control.
AB  - An online infection prevention and control programme for medical students was
      developed and assessed. There was a statistically significant improvement
      (P<0.0001) in the knowledge base among 517 students after completing two modules.
      The majority of students who completed the evaluation were positive about the
      learning experience.

PMID- 21945067
TI  - Efficacy of intravascular catheter lock solutions containing preservatives in the
      prevention of microbial colonization.
AB  - There is little published evidence regarding whether heparin lock solutions
      containing preservatives prevent catheter-related infections. However, adverse
      effects from preservative-containing flushes have been documented in neonates,
      leading many hospitals to avoid their use altogether. Infection control records
      from 1982 to 2008 at St. Jude Children's Research Hospital (SJCRH) were reviewed
      regarding the incidence of catheter-related infections and the use of
      preservative-containing intravenous locks. In addition, the antimicrobial
      activities of heparin lock solution containing the preservatives parabens
      (0.165%) or benzyl alcohol (0.9%), and 70% ethanol were examined against
      Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, Bacillus
      cereus, Pseudomonas aeruginosa and Candida albicans, and compared with
      preservative-free saline with and without heparin. Growth was assessed after
      exposure to test solutions for 0, 2, 4 and 24h at 35  degrees C. The activities
      of preservatives were assessed against both planktonic (free-floating) and
      sessile (biofilm-embedded) micro-organisms using the MBEC Assay. Infection
      control records revealed two periods of increased catheter-related infections,
      corresponding with two intervals when preservative-free heparin was used at
      SJCRH. Heparin solution containing preservatives demonstrated significant
      antimicrobial activity against both planktonic and sessile forms of all six
      microbial species. Ethanol demonstrated the greatest antimicrobial activity,
      especially following short incubation periods. Heparin lock solutions containing
      the preservatives parabens or benzyl alcohol, and 70% ethanol demonstrated
      significant antimicrobial activity against both planktonic and sessile micro
      organisms commonly responsible for catheter-related infections. These findings,
      together with the authors' historical infection control experience, support the
      use of preservatives in intravenous lock solutions to reduce catheter related
      infections in patients beyond the neonatal period.

PMID- 21945068
TI  - [Validation of a short form of the function dimension of the WOMAC
      questionnaire].
AB  - OBJECTIVE: The aim of this prospective study was to evaluate the validity,
      reliability and responsiveness of the Spanish version of the 7-item short-form of
      the function dimension of the Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC). METHODS: We conducted a prospective 1-year cohort
      study that included 459 patients on the waiting list for total knee or hip
      replacement. The WOMAC and EQ-5D questionnaires were sent at four time points:
      baseline and at 3, 6 and 12 months post-surgery. Based on a previously shortened
      scale, we performed a validation process with Rasch analysis and agreement
      measured by Bland-Altman plots. RESULTS: The values of Spearman's rho and Lin
      concordance coefficients between the full and short-form ranged from 0.96 to
      0.98. Differences were statistically significant (p < 0.001) among the three
      groups of severity measured by a item in the EQ-5D. The two Bland-Altman plots
      showed no systematic differences and agreement was not dependent on the severity
      score. The short form fitted the Rasch model. Cronbach's alpha coefficients were
      higher than 0.85. Responsiveness was higher than 1.27 and 1.72 in knee and hip
      replacement, respectively. CONCLUSIONS: The Spanish 7-item short form of the
      WOMAC function dimension is valid, reliable and responsive for patients with
      total joint replacement. The use of this version will reduce the burden on
      patients in both clinical studies and clinical practice.

PMID- 21945069
TI  - [Impact of the 28/2005 Spanish smoking law on second-hand smoke exposure in
      Barcelona].
AB  - OBJECTIVE: To assess the impact of the 28/2005 Spanish smoking law on exposure to
      second-hand smoke (SHS) in Barcelona. METHODS: We performed a pre-post evaluation
      study. Two cross-sectional surveys were compared. Data were obtained from the
      Barcelona Health Surveys of 2000 and 2006. The prevalence of SHS exposure among
      non-smoking adults was analyzed by setting (home, workplace and leisure time) and
      sociodemographic variables. RESULTS: SHS exposure in non-smokers significantly
      decreased between 2000 and 2006 (p < 0.01). Odds ratios adjusted by sex, age and
      social class were 0.7 (95% CI: 0.6-0.8) for home and 0.2 (95% CI: 0.2-0.3) for
      workplace exposure in 2006 compared with 2000. In both settings, the decrease in
      exposure was greater in the higher social classes. After the implementation of
      the law, almost 50% of the population remained exposed to SHS during leisure
      time, younger people being the most exposed (83.5%). CONCLUSION: After the
      implementation of the law, the prevalence of SHS exposure in non-smokers in
      Barcelona decreased significantly in workplaces and in the home. Nevertheless,
      nearly half of the population remained exposed to SHS during leisure time.

PMID- 21945070
TI  - Type I and III collagen degradation products in serum predict patient survival in
      head and neck squamous cell carcinoma.
AB  - Cancer invasion induces extracellular matrix remodeling and collagen degradation.
      The aim of this study was to assess whether serum levels of type I and III
      collagen degradation products were associated with patient survival in head and
      neck squamous cell carcinoma (HNSCC). A novel enzyme immunoassay was developed
      for measuring type III collagen N-terminal telopeptide (IIINTP) in human serum
      samples. In addition, type I collagen C-terminal telopeptide (ICTP), matrix
      metalloprotease-8 (MMP-8) and tissue inhibitor of metalloproteases-1 (TIMP-1)
      were assessed in 205 blood samples from HNSCC patients. High levels of serum ICTP
      and IIINTP and plasma TIMP-1 were associated with poor survival. The
      concentration of ICTP was associated with levels of IIINTP and TIMP-1. The plasma
      concentration of MMP-8 was associated with tumor stage, but not with survival or
      levels of ICTP, IIINTP or TIMP-1 suggesting that other collagenases/proteases are
      responsible for the cleavage of type I and type III collagens. The rate of type I
      and type III collagen degradation is associated with patient survival and can be
      used as a prognostic marker in HNSCC.

PMID- 21945071
TI  - Sonic hedgehog signaling promotes growth of oral squamous cell carcinoma cells
      associated with bone destruction.
AB  - Sonic hedgehog (Shh) and its signaling have been identified in several human
      cancers, and increased levels of its expression appear to correlate with disease
      progression and metastasis. However, the role of Shh in bone destruction
      associated with oral squamous cell carcinomas, which frequently invade the
      maxilla or the mandible, is still unclear. In this study we show that the use of
      siRNA for Shh to block SHH secreted by SAS oral squamous cell carcinoma cells
      suppressed the tumor growth and tumor angiogenesis of subcutaneous SAS xenografts
      in vivo. Moreover, blockade of Shh in SAS cells decreased tumor growth and
      osteoclast number in a tibial metaphysis mouse model. Significantly, we clearly
      show that SHH stimulated osteoclast formation in a co-culture system consisting
      of murine bone stromal ST2 cells and murine CD11b(+) bone marrow cells. These
      findings suggest that Shh signaling is a potential target for the treatment of
      oral squamous cell carcinoma associated with bone destruction.

PMID- 21945072
TI  - Different genes influence toluene- and ethanol-induced locomotor impairment in C.
      elegans.
AB  - BACKGROUND: The abused volatile solvent toluene shares many behavioral effects
      with classic central nervous system depressants such as ethanol. Similarities
      between toluene and ethanol have also been demonstrated using in vitro
      electrophysiology. Together, these studies suggest that toluene and ethanol may
      be acting, at least in part, via common mechanisms. METHODS: We used the genetic
      model, Caenorhabditis elegans, to examine the behavioral effects of toluene in a
      simple system, and used mutant strains known to have altered responses to other
      CNS depressants to examine the involvement of those genes in the motor effects
      induced by toluene. RESULTS: Toluene vapor brings about an altered pattern of
      locomotion in wild-type worms that is visibly distinct from that generated by
      ethanol. Mutants of the slo-1, rab-3 and unc-64 genes that are resistant to
      ethanol or the volatile anesthetic halothane show no resistance to toluene. A
      mutation in the unc-79 gene results in hypersensitivity to ethanol, halothane and
      toluene indicating a possible convergence of mechanisms of the three compounds.
      We screened for, and isolated, two mutations that generate resistance to the
      locomotor depressing effects of toluene and do not alter sensitivity to ethanol.
      CONCLUSIONS: In C. elegans, ethanol and toluene have distinct behavioral effects
      and minimal overlap in terms of the genes responsible for these effects. These
      findings demonstrate that the C. elegans model system provides a unique and
      sensitive means of delineating both the commonalities as well as the differences
      in the neurochemical effects of classical CNS depressants and abused volatile
      inhalants.

PMID- 21945074
TI  - miRNAs control tracheal chondrocyte differentiation.
AB  - The specific program that enables the stereotypic differentiation of specialized
      cartilages, including the trachea, is intrinsically distinct from the program
      that gives rise to growth plate hypertrophic chondrocytes. For example, Snail1 is
      an effector of FGF signaling in growth plate pre-hypertrophic chondrocytes, but
      it derails the normal program of permanent chondrocytes, repressing the
      transcription of Aggrecan and Collagen type 2a1 (Col2a1). Here we show that miRNA
      activity is essential for normal trachea development and that miR-125b and miR
      30a/c keep Snail1 at low levels, thus enabling full functional differentiation of
      Col2a1 tracheal chondrocytes. Specific inhibition of miR-125b and miR-30a/c in
      chondrocytes or Dicer1 knockout in the trachea, de-repress Snail1. As a
      consequence, the transcription of Aggrecan and Col2a1 is hampered and
      extracellular matrix deposition is decreased. Our data reveals a new miRNA
      pathway that is safekeeping the specific genetic program of differentiated and
      matrix-producing tracheal chondrocytes from acquisition of unwanted signals. This
      pathway may improve understanding of human primary tracheomalacia and improve
      protocols for cartilage tissue engineering.

PMID- 21945073
TI  - Subnuclear development of the zebrafish habenular nuclei requires ER translocon
      function.
AB  - The dorsal habenular nuclei (Dh) of the zebrafish are characterized by
      significant left-right differences in gene expression, anatomy, and connectivity.
      Notably, the lateral subnucleus of the Dh (LsDh) is larger on the left side of
      the brain than on the right, while the medial subnucleus (MsDh) is larger on the
      right compared to the left. A screen for mutations that affect habenular
      laterality led to the identification of the sec61a-like 1(sec61al1) gene. In
      sec61al1(c163) mutants, more neurons in the LsDh and fewer in the MsDh develop on
      both sides of the brain. Generation of neurons in the LsDh occurs more rapidly
      and continues for a longer time period in mutants than in WT. Expression of Nodal
      pathway genes on the left side of the embryos is unaffected in mutants, as is the
      left sided placement of the parapineal organ, which promotes neurogenesis in the
      LsDh of WT embryos. Ultrastructural analysis of the epithalamus indicates that
      ventricular precursor cells, which form an epithelium in WT embryos, lose apical
      basal polarity in sec61al1(c163) mutants. Our results show that in the absence of
      sec61al1, an excess of precursor cells for the LsDh exit the ventricular region
      and differentiate, resulting in formation of bilaterally symmetric habenular
      nuclei.

PMID- 21945075
TI  - Rac1 GTPase-deficient mouse lens exhibits defects in shape, suture formation,
      fiber cell migration and survival.
AB  - Morphogenesis and shape of the ocular lens depend on epithelial cell elongation
      and differentiation into fiber cells, followed by the symmetric and compact
      organization of fiber cells within an enclosed extracellular matrix-enriched
      elastic capsule. The cellular mechanisms orchestrating these different events
      however, remain obscure. We investigated the role of the Rac1 GTPase in these
      processes by targeted deletion of expression using the conditional gene knockout
      (cKO) approach. Rac1 cKO mice were derived from two different Cre (Le-Cre and MLR
      10) transgenic mice in which lens-specific Cre expression starts at embryonic day
      8.75 and 10.5, respectively, in both the lens epithelium and fiber cells. The Le
      Cre/Rac1 cKO mice exhibited an early-onset (E12.5) and severe lens phenotype
      compared to the MLR-10/Rac1 cKO (E15.5) mice. While the Le-Cre/Rac1 cKO lenses
      displayed delayed primary fiber cell elongation, lenses from both Rac1 cKO
      strains were characterized by abnormal shape, impaired secondary fiber cell
      migration, sutural defects and thinning of the posterior capsule which often led
      to rupture. Lens fiber cell N-cadherin/beta-catenin/Rap1/Nectin-based cell-cell
      junction formation and WAVE-2/Abi-2/Nap1-regulated actin polymerization were
      impaired in the Rac1 deficient mice. Additionally, the Rac1 cKO lenses were
      characterized by a shortened epithelial sheet, reduced levels of extracellular
      matrix (ECM) proteins and increased apoptosis. Taken together, these data uncover
      the essential role of Rac1 GTPase activity in establishment and maintenance of
      lens shape, suture formation and capsule integrity, and in fiber cell migration,
      adhesion and survival, via regulation of actin cytoskeletal dynamics, cell
      adhesive interactions and ECM turnover.

PMID- 21945076
TI  - Mutations in Traf3ip1 reveal defects in ciliogenesis, embryonic development, and
      altered cell size regulation.
AB  - Tumor necrosis factor alpha receptor 3 interacting protein 1 (Traf3ip1), also
      known as MIPT3, was initially characterized through its interactions with
      tubulin, actin, TNFR-associated factor-3 (Traf3), IL-13R1, and DISC1. It
      functions as an inhibitor of IL-13-mediated phosphorylation of Stat6 and in
      sequestration of Traf3 and DISC1 to the cytoskeleton. Studies of the Traf3ip1
      homologs in C. elegans (DYF-11), Zebrafish (elipsa), and Chlamydomonas (IFT54)
      revealed that the protein localizes to the cilium and is required for
      ciliogenesis. Similar localization data has now been reported for mammalian
      Traf3ip1. This raises the possibility that Traf3ip1 has an evolutionarily
      conserved role in mammalian ciliogenesis in addition to its previously indicated
      functions. To evaluate this possibility, a Traf3ip1 mutant mouse line was
      generated. Traf3ip1 mutant cells are unable to form cilia. Homozygous Traf3ip1
      mutant mice are not viable and have both neural developmental defects and
      polydactyly, phenotypes typical of mouse mutants with ciliary assembly defects.
      Furthermore, in Traf3ip1 mutants the hedgehog pathway is disrupted, as evidenced
      by abnormal dorsal-ventral neural tube patterning and diminished expression of a
      hedgehog reporter. Analysis of the canonical Wnt pathway indicates that it was
      largely unaffected; however, specific domains in the pharyngeal arches have
      elevated levels of reporter activity. Interestingly, Traf3ip1 mutant embryos and
      cells failed to show alterations in IL-13 signaling, one of the pathways
      associated with its initial discovery. Novel phenotypes observed in Traf3ip1
      mutant cells include elevated cytosolic levels of acetylated microtubules and a
      marked increase in cell size in culture. The enlarged Traf3ip1 mutant cell size
      was associated with elevated basal mTor pathway activity. Taken together, these
      data demonstrate that Traf3ip1 function is highly conserved in ciliogenesis and
      is important for proper regulation of a number of essential developmental and
      cellular pathways. The Traf3ip1 mutant mouse and cell lines will provide valuable
      resources to assess cilia function in mammalian development and also serve as a
      tool to explore the potential connections between cilia and cytoskeletal
      dynamics, mTor regulation, and cell volume control.

PMID- 21945078
TI  - Clinical and patient-reported outcomes of patients with four major lower
      extremity arthroplasties.
AB  - Few studies report the outcomes of patients treated with total joint arthroplasty
      of both hips and both knees. We present the outcomes of 14 patients with total
      joint arthroplasty of both hips and both knees using validated outcome measures.
      Eleven patients (79%) were satisfied at final review. Ten patients (71%) required
      revision surgery of at least one joint. Clinical, functional, radiographic, and
      patient-reported outcomes were consistent with previously reported outcomes in
      the literature. Mean Timed Up and Go test was 32 seconds (6-158). Mean Berg
      Balance Scale was 38.5 (4-55). Good outcomes can be achieved in this group of
      patients with high levels of satisfaction despite the frequent need for revision
      surgery. Importantly, it was recognized that these patients have a high risk of
      falls and must be educated in measures for fall prevention.

PMID- 21945077
TI  - P190A RhoGAP is required for mammary gland development.
AB  - P190A and p190B Rho GTPase activating proteins (GAPs) are essential genes that
      have distinct, but overlapping roles in the developing nervous system. Previous
      studies from our laboratory demonstrated that p190B is required for mammary gland
      morphogenesis, and we hypothesized that p190A might have a distinct role in the
      developing mammary gland. To test this hypothesis, we examined mammary gland
      development in p190A-deficient mice. P190A expression was detected by in situ
      hybridization in the developing E14.5day embryonic mammary bud and within the
      ducts, terminal end buds (TEBs), and surrounding stroma of the developing virgin
      mammary gland. In contrast to previous results with p190B, examination of p190A
      heterozygous mammary glands demonstrated that p190A deficiency disrupted TEB
      morphology, but did not significantly delay ductal outgrowth indicating
      haploinsufficiency for TEB development. To examine the effects of homozygous
      deletion of p190A, embryonic mammary buds were rescued by transplantation into
      the cleared fat pads of SCID/Beige mice. Complete loss of p190A function
      inhibited ductal outgrowth in comparison to wildtype transplants (51% vs. 94% fat
      pad filled). In addition, the transplantation take rate of p190A deficient whole
      gland transplants from E18.5 embryos was significantly reduced compared to
      wildtype transplants (31% vs. 90%, respectively). These results suggest that
      p190A function in both the epithelium and stroma is required for mammary gland
      development. Immunostaining for p63 demonstrated that the myoepithelial cell
      layer is disrupted in the p190A deficient glands, which may result from the
      defective cell adhesion between the cap and body cell layers detected in the
      TEBs. The number of estrogen- and progesterone receptor-positive cells, as well
      as the expression levels of these receptors was increased in p190A deficient
      outgrowths. These data suggest that p190A is required in both the epithelial and
      stromal compartments for ductal outgrowth and that it may play a role in mammary
      epithelial cell differentiation.

PMID- 21945079
TI  - Properties of the patient administered questionnaires: new scales measuring
      physical and psychological symptoms of hip and knee disorders.
AB  - The Patient Administered Questionnaires (PAQ) incorporate physical and
      psychological symptoms into one scale and permit more comprehensive self-reports
      for hip and knee disorders. We tested the psychometric properties of the PAQ-Hip
      and PAQ-Knee. Correlations between baseline PAQ-Hip and Western Ontario and
      McMaster Universities Osteoarthritis Index (WOMAC) were .39 to .72 (n = 102), .39
      to .69 for score change (n = 68 post-total hip arthroplasty), and most kappa
      values > .60 (n = 50). Correlations between baseline PAQ-Knee and WOMAC were .35
      to .64 (n = 100), .62 to .79 for score change (n = 43 post-total knee
      arthroplasty), and most kappa values >.60 (n = 51). For both scales, effect sizes
      were higher than for the WOMAC, and there was modest correlation between physical
      and psychological questions, indicating these concepts are not completely
      interchangeable. Thus, the PAQ scales have strong psychometric properties and are
      unique compared with existing scales by including physical and psychological
      symptoms.

PMID- 21945080
TI  - High-flex rotating platform knee implants: two- to 6-year results of a
      prospective study.
AB  - We prospectively enrolled 48 patients (53 knees), scheduled for high-flex
      posterior-stabilized rotating platform knee implant arthroplasty (PFCSigmaRPF) to
      our study. Performance of this implant, introduced in 2005, has been reported
      upon only up to 2 years. We report its 2- to 6-year postoperative clinical and
      radiographic results in 47 patients (52 knees). Mean Knee Society score improved
      from 35.7 to 96. Mean function score improved from 55.2 to 90.6. Postoperative
      knee flexion averaged 130 degrees  (95 degrees -155 degrees ), 81% patients could
      sit cross legged, 53% could sit on floor, and 21% could squat. Kaplan-Meier
      survival rate was 100% at average 50.2 months (26-72 months). No patient had any
      spin-out of rotating bearing. Supervised radiographs were analyzed, which showed
      no osteolysis or component loosening.

PMID- 21945081
TI  - Three-in-one nerve block with different concentrations of bupivacaine in total
      knee arthroplasty: randomized, placebo-controlled, double-blind trial.
AB  - Pain after total knee arthroplasty may be severe and lead to adverse outcomes.
      Using 2 concentrations of bupivacaine, we investigated 3-in-1 nerve block's
      effect on pain control, narcotic use, sedation, and patient satisfaction. One
      hundred five patients undergoing unilateral total knee arthroplasty were
      randomized into 3 groups: low-dose or high-dose bupivacaine or placebo. Ninety
      nine patients completed the study. Three-in-1 nerve block reduced patient
      controlled opioid analgesia usage and improved pain relief in the early
      postoperative period but had little effect beyond postoperative day 1. There were
      no significant differences among groups with respect to nausea or sedation.
      Patients in each group exhibited high overall satisfaction. Low-dose bupivacaine
      was superior to high-dose bupivacaine for pain relief, narcotic consumption, and
      patient satisfaction in the early postoperative period.

PMID- 21945082
TI  - Effective detection of human noroviruses in Hawaiian waters using enhanced RT-PCR
      methods.
AB  - The current recreational water quality criteria using growth-based measurements
      of fecal indicator bacteria (FIB) concentration have their limitations for
      swimmer protection. To evaluate the possible use of enteric viruses as an
      improved indicator of human sewage contamination in recreational waters for
      enhanced health risk assessment, human norovirus (huNoV) was tested as a model in
      this study. To establish a highly sensitive protocol for effective huNoV
      detection in waters, 16 published and newly designed reverse transcription
      polymerase chain reaction (RT-PCR) primer pairs specific for huNoV genogroup I
      (GI) and genogroup II (GII) were comparatively evaluated side-by-side using
      single sources of huNoV RNA stock extracted from local clinical isolates. Under
      optimized conditions, these RT-PCR protocols shared a very different pattern of
      detection sensitivity for huNoV. The primer sets COG2F/COG2R and QNIF4/NV1LCR
      were determined to be the most sensitive ones for huNoV GII and GI, respectively,
      with up to 10(5)- and 10(6)-fold more sensitive as compared to other sets tested.
      These two sensitive protocols were validated by positive detection of huNoV in
      untreated and treated urban wastewater samples. In addition, these RT-PCR
      protocols enabled detection of the prevalence of huNoV in 5 (GI) and 10 (GII) of
      16 recreational water samples collected around the island of O'ahu, which was
      confirmed by DNA sequencing and sequence analysis. Findings from this study
      support the possible use of enteric viral pathogens for environmental monitoring
      and argue the importance and essentiality for such monitoring activity to ensure
      a safe use of recreational waters.

PMID- 21945083
TI  - Heparin-binding EGF-like growth factor is required for synaptic plasticity and
      memory formation.
AB  - Heparin-binding epidermal growth factor-like growth factor (HB-EGF), a member of
      epidermal growth factor (EGF) family, is a potent mitogenic peptide for various
      types of cells. HB-EGF is widely expressed in central nervous system, including
      hippocampus and cerebral cortex, and is considered to play pivotal roles in the
      developing and adult nervous system. In this study, we assessed the role of HB
      EGF in learning and memory by testing HB-EGF conditional knock-out mice (KO) in
      two different learning tasks, and evaluated the long-term potentiation (LTP) in
      hippocampus slices from these mice. The HB-EGF KO mice were impaired in spatial
      memory in the Morris water maze and in fear learning in a passive avoidance test.
      HB-EGF KO mice also showed an impaired LTP, and reduction in activity of
      Ca2+/calmodulin-dependent protein kinase II (CaMKII) and phosphorylated GluR1. We
      also found that the levels of neurotrophic factors, such as nerve growth factor
      (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), or glial
      cell line-derived neurotrophic factor (GDNF), were altered in several brain
      regions in the HB-EGF KO mice. These results confirm the importance of the HB-EGF
      in synaptic plasticity and memory formation.

PMID- 21945084
TI  - Effects of clozapine and N-desmethylclozapine on synaptic transmission at
      hippocampal inhibitory and excitatory synapses.
AB  - Clozapine is the first atypical antipsychotic, and improves positive and negative
      symptoms of many patients with schizophrenia resistant to treatment with other
      antipsychotic agents. Clozapine induces minimal extrapyramidal side effects, but
      is more often associated with seizures. A large number of studies have been
      conducted to elucidate pharmacological profiles of clozapine and its major active
      metabolite, N-desmethylclozapine (NDMC). However, there are only a limited number
      of electrophysiological studies examining their effects on synaptic transmission.
      In this study, we examined effects of clozapine and NDMC on synaptic transmission
      by measuring inhibitory and excitatory postsynaptic currents in rat cultured
      hippocampal neurons. We found that clozapine and NDMC have qualitatively similar
      actions. They depressed the inhibitory transmission at 1-30 MUM, and the
      excitatory transmission at 30 MUM, the former being much more sensitive. The
      depression of IPSCs by 30 MUM of these drugs was associated with an increase in
      the paired-pulse ratio. The GABA-induced currents were suppressed by these drugs,
      but less sensitive than IPSCs. The AMPA-induced currents were slightly
      potentiated by these drugs at 30 MUM. At 30 MUM, clozapine and NDMC slightly
      suppressed Ca(2+) and Na(+) channels. These results strongly suggest that
      clozapine and NMDC depress the inhibitory synaptic transmission mainly by
      antagonizing postsynaptic GABA(A) receptors, but at higher concentrations
      additionally by acting on presynaptic site, possibly in part through inhibition
      of presynaptic Ca(2+) and Na(+) channels. Preferential depression of inhibitory
      synaptic transmission by clozapine and NDMC might contribute to therapeutic
      actions and/or side-effects of clozapine.

PMID- 21945086
TI  - The effect of blood pressure (37 vs 45 mmHg) and carotid occlusion duration (8 vs
      10 min) on CA1-4 neuronal damage when using isoflurane in a global cerebral
      ischemia rat model.
AB  - This study presents our findings on the extent of neuronal damage in the
      hippocampal CA1-4 subfields following global (forebrain) cerebral ischemia in
      rats when using different blood pressure levels (37 vs 45 mmHg) and bilateral
      carotid occlusion durations (8 vs 10 min) under isoflurane anesthesia. We
      observed that global ischemia induced at a blood pressure of 37 mmHg resulted in
      high-grade CA1 neuron injury (>90%) at either duration of carotid occlusion. In
      contrast, global ischemia induced at a blood pressure of 45 mmHg resulted in
      either high-grade CA1 neuronal loss or a neuronal loss of ~50% or less. We also
      noted that a post-reperfusion EEG recovery time (return of burst suppression
      spikes) of >12 min was associated with an 85% rate of high-grade CA1 neuronal
      injury. Neuronal loss in the other hippocampal subfields did not differ
      significantly between any of the 4 different model parameters tested. In these
      subfields ~55% neuronal loss occurred in the CA2 subfield, and ~30% in the CA3
      and CA4 subfields. These findings highlight the need to assess different model
      parameters in order to achieve consistent high-grade CA1 neuronal damage, which,
      among other experimental outcomes, will improve the ability to uncover
      therapeutic effects using the least possible animals when assessing a
      neuroprotective treatment.

PMID- 21945085
TI  - Out and about: association of the built environment with physical activity
      behaviors of adolescent females.
AB  - Locational data, logged on portable GPS units and matched with accelerometer
      data, was used to examine associations of the built environment with physical
      activity and sedentary behaviors of adolescent females. In a sample of 293
      adolescent females aged 15 to 18 years old in Minneapolis and San Diego, the
      built environment around each GPS point and its corresponding sedentary, light,
      and moderate-to-vigorous intensity physical activity was examined using random
      intercept multinomial logistic regression models. The odds of higher physical
      activity intensity (3-level outcome: sedentary, light, MVPA) were higher in
      places with parks, schools, and high population density, during weekdays, and
      lower in places with more roads and food outlets. Understanding the places where
      physical activity and sedentary behaviors occur appears to be a promising
      strategy to clarify relationships and inform policy aimed at increasing physical
      activity and reducing sedentary behaviors.

PMID- 21945087
TI  - Circulating IL-6 contributes to peripheral LPS-induced mPGES-1 expression in the
      rat brain.
AB  - Interleukin-(IL)6 is the most prominent circulating cytokine induced by systemic
      infection and inflammation, and the main humoral mediator to the brain in fever.
      We have previously demonstrated that the PG-pathway, the ultimate step in fever
      generation, is activated by circulating IL-6 by triggering the expression of the
      rate limiting enzyme cyclooxygenase (COX)2 in the brain. Downstream of COX2,
      another enzyme, microsomal PG synthase (mPGES)-1 has also been implicated in the
      inflammatory response but relatively little is known about its role in cytokine
      mediated inflammation. Here, we investigated for the first time the direct role
      of circulating IL-6 in brain and peripheral mPGES-1-expression. Rats were either
      treated with LPS into a subcutaneous air pouch combined with intraperitoneal
      injection of a rat specific IL-6 antiserum (AS) or received a single
      intraperitoneal injection of IL-6. LPS increased the expression of mPGES-1 mRNA
      in the brain, liver and brown adipose tissue (BAT) but not epididymal white (eW)
      adipose tissue. This response was reversed by IL-6AS in LPS-injected animals for
      the brain and liver. IL-6-treatment only induced mPGES-1-expression in the brain
      and its immunoreactivity co-localized with phosphorylated signal transducer and
      activator of transcription (STAT)3 the main transcription factor activated by IL
      6. Moreover, circulating IL-6 levels and the suppressor of cytokine signaling
      (SOCS)-3, a broadly used marker of STAT3-activation, strongly correlated with
      mPGES-1 expression in the brain. In summary, we have clearly shown that
      circulating IL-6 can directly induce mPGES-1 linked to STAT3-activation in the
      brain but not peripheral tissues of rats during localised peripheral
      inflammation.

PMID- 21945088
TI  - A head-to-head comparison of 16 cataract surgery outcome questionnaires.
AB  - PURPOSE: To investigate the responsiveness of 16 questionnaires used in cataract
      surgery outcomes. DESIGN: Prospective, observational study. PARTICIPANTS:
      Patients at the Ophthalmology Eye Clinic, Flinders Medical Centre, Adelaide,
      Australia, and 1 matched eye clinic in Sweden. METHODS: Sixteen Rasch-scaled
      cataract surgery questionnaires were completed before and 6 months after surgery.
      These were: the Cataract Symptom Scale, 6 versions of the National Eye Institute
      Visual Function Questionnaire, the Quality of Life and Vision Function
      Questionnaire, the Cataract TyPE Specification, the Visual Activities
      Questionnaire, the Visual Disability Assessment (VDA), the Visual Function and
      Quality of Life questionnaire, the Visual Function Index, Catquest-9SF, the
      Visual Symptoms and Quality of Life questionnaire, and the Cataract Outcomes
      Questionnaire. Responsiveness was calculated with the effect size (ES) statistic
      (change in questionnaire score divided by pooled standard deviation of the
      preoperative and postoperative scores). MAIN OUTCOME MEASURES: Questionnaire
      responsiveness to cataract surgery (ability to detect clinically important
      change). RESULTS: All 16 questionnaires and their subscales were responsive to
      cataract surgery, with visual functioning scales being more responsive than
      socioemotional scales and some subscales being less responsive. The largest ES
      was for the Catquest-9SF (1.45; 95% confidence interval [CI], 1.22-1.67), which
      was the only instrument with a mean and 95% CI of more than 1.0 (very large ES).
      Three measures had very large ESs and 95% CIs of more than 0.80 (large ES): the
      VDA (activity limitations and subscale) and the Cataract Outcomes Questionnaire,
      although their 95% CIs overlapped with a number of other instruments.
      CONCLUSIONS: The Catquest-9SF is short and highly responsive to cataract surgery,
      and so is ideal for measuring visual functioning outcomes. Other instruments may
      be preferred to measure different constructs. FINANCIAL DISCLOSURE(S): The
      author(s) have no proprietary or commercial interest in any materials discussed
      in this article.

PMID- 21945089
TI  - Bioelectronic nose with high sensitivity and selectivity using chemically
      functionalized carbon nanotube combined with human olfactory receptor.
AB  - Single-walled carbon nanotubes (swCNTs) hold great promise for use as molecular
      wires because they exhibit high electrical conductivity and chemical stability.
      However, constructing swCNT-based transducer devices requires controlled
      strategies for assembling biomolecules on swCNTs. In this study, we proposed a
      chemically modified swCNT. The swCNT was functionalized with 1,5
      diaminonaphthalene via pi-stacking, for reliable attachment of the human
      olfactory receptor 2AG1 (hOR2AG1). The human olfactory receptor was then
      anchored. We investigated the use of this functionalized CNT in the fabrication
      of a highly sensitive and selective bioelectronic nose. For the bioelectronic
      nose, the swCNT-field effect transistor (FET) platform was composed of
      polyethylene glycol (PEG)-coated regions to prevent non-specific absorption and
      chemically modified swCNTs regions containing hOR2AG1, which can bind to the
      specific odorant. This approach allowed us to create well-defined micron-scale
      patterns of hOR2AG1 on the swCNTs. Our bioelectronic nose displayed ultrahigh
      sensitivity down to concentrations as low as 1fM due to the enhanced hOR2AG1
      odorant interaction through the tight binding of hOR2AG1 on the chemically
      modified swCNTs. In addition, the approach described here may provide an
      alternative route for multiplexed detection of diverse odorants and to improve
      the sensitivity of sensor devices.

PMID- 21945091
TI  - [Old drugs and late intervention - can we improve as the struggle for universal
      primary percutaneous coronary intervention continues?].

PMID- 21945092
TI  - [Trends in leisure time physical activity practice in the 1995-2005 period in
      Girona].
AB  - INTRODUCTION AND OBJECTIVES: The aims of the study were: to describe the
      distribution of physical activity practice; to determine the prevalence and
      trends of sedentary lifestyle in the population aged 35 to 74 years of Girona in
      the 1995-2005 period; and to identify the variables associated to sedentary
      lifestyle at the population level. METHODS: Data from three independent
      population-based cross-sectional studies undertaken in 1995 (n=1419), 2000
      (n=2499), and 2005 (n=5628) were analyzed. Physical activity was measured using
      the Minnesota Leisure Time Physical Activity questionnaire. Sedentary lifestyle
      was defined as an energy expenditure in moderate physical activity (4-5.5 METs)
      <675 kcal/week or <420 kcal/week in intense PA (>= 6 METs). Logistic regression
      was used to determine the variables associated with sedentary lifestyle. RESULTS:
      The age-standardized prevalence of sedentary lifestyle was 53.8%, 39.5%, and
      32.6% in 1995, 2000, and 2005 respectively. The prevalence of sedentary lifestyle
      has decreased especially in women older than 50 years living in the urban areas.
      An increase in light and moderate physical activity practice in men older than 50
      years and in light physical activity practice in women older than 50 years was
      observed. Female gender, age, smoking and lower educational level were associated
      with a higher prevalence of sedentary lifestyle. CONCLUSIONS: Prevalence of
      sedentary lifestyle has decreased in the 1995-2005 period in Girona, especially
      in women, but is still high. Health promotion programs should include physical
      activity practice as a key element and should take into account gender and social
      inequalities.

PMID- 21945093
TI  - Neurologic function during developmental and adult stages in Dab1(scm)
      (scrambler) mutant mice.
AB  - Homozygous Dab1(scm) mouse mutants with cell ectopias in cerebellar cortex,
      hippocampus, and neocortex were compared to non-ataxic controls on the SHIRPA
      primary screening battery on postnatal days 8, 15, and 22, as well as in the
      adult period. Dab1(scm) mutants were distinguished from non-ataxic controls as
      early as postnatal day 8 based on body tremor, gait anomalies, and body weight.
      On postnatal day 15, motor coordination deficits were evident on horizontal bar
      and inclined or vertical grid tests in association with a weaker grip strength.
      Likewise, mutants were distinguished from controls on drop righting and hindpaw
      clasping tests. Further differences were detected on postnatal day 22 in the form
      of fewer visual placing, touch escape, trunk curl, freezing, and vocalization
      responses, as well as squares traversed in the open-field. Evaluation at the
      adult age demonstrated similar impairments, indicative of permanent motor
      alterations. Neuronal metabolic activity was estimated by cytochrome oxidase
      histochemistry on cerebellar sections. Cerebellar cortical layers and efferent
      deep nuclei of Dab1(scm) mice appeared hypometabolic relative to non-ataxic mice
      despite normal metabolism in both regular and ectopic Purkinje cells.

PMID- 21945095
TI  - Mcm10 interacts with Rad4/Cut5(TopBP1) and its association with origins of DNA
      replication is dependent on Rad4/Cut5(TopBP1).
AB  - Initiation of DNA replication in eukaryotes is a highly conserved and ordered
      process involving the co-ordinated, stepwise association of distinct proteins at
      multiple origins of replication throughout the genome. Here, taking
      Schizosaccharomyces pombe as a model, the role of Rad4(TopBP1) in the assembly of
      the replication complex has been examined. Quantitative chromatin
      immunoprecipitation experiments confirm that Rad4(TopBP1) associates with origins
      of DNA replication and, in addition, demonstrate that the protein is not present
      within the active replisome. A direct interaction between Rad4(TopBP1) and Mcm10
      is shown and this is reflected in the Rad4(TopBP1)-dependent origin association
      of Mcm10. Rad4(TopBP1) is also shown to interact with Sld2 and Sld3 and to be
      required for the stable origin association of these two proteins. Rad4(TopBP1)
      chromatin association at stalled replication forks was found to be dependent upon
      the checkpoint protein Rad9, which was not required for Rad4(TopBP1) origin
      association. Comparison of the levels of chromatin association at origins of
      replication and stalled replication forks and the differential requirement for
      Rad9 suggest functional differences for Rad4(TopBP1) at these distinct sites.

PMID- 21945094
TI  - PIF1 disruption or NBS1 hypomorphism does not affect chromosome healing or fusion
      resulting from double-strand breaks near telomeres in murine embryonic stem
      cells.
AB  - Telomerase serves to maintain telomeric repeat sequences at the ends of
      chromosomes. However, telomerase can also add telomeric repeat sequences at DNA
      double-strand breaks (DSBs), a process called chromosome healing. Here, we
      employed a method of inducing DSBs near telomeres to query the role of two
      proteins, PIF1 and NBS1, in chromosome healing in mammalian cells. PIF1 was
      investigated because the PIF1 homolog in Saccharomyces cerevisiae inhibits
      chromosome healing, as shown by a 1000-fold increase in chromosome in PIF1
      deficient cells. NBS1 was investigated because the functional homolog of NBS1 in
      S. cerevisiae, Xrs2, is part of the Mre11/Rad50/Xrs2 complex that is required for
      chromosome healing due to its role in the processing of DSBs and recruitment of
      telomerase. We found that disruption of mPif1 had no detectable effect on the
      frequency of chromosome healing at DSBs near telomeres in murine embryonic stem
      cells. Moreover, the Nbs1(DeltaB) hypomorph, which is defective in the processing
      of DSBs, also had no detectable effect on the frequency of chromosome healing,
      DNA degradation, or gross chromosome rearrangements (GCRs) that result from
      telomeric DSBs. Although we cannot rule out small changes in chromosome healing
      using this system, it is clear from our results that knockout of PIF1 or the
      Nbs1(DeltaB) hypomorph does not result in large differences in chromosome healing
      in murine cells. These results represent the first genetic assessment of the role
      of these proteins in chromosome healing in mammals, and suggest that murine cells
      have evolved mechanisms to ensure the functional redundancy of Pif1 or Nbs1 in
      the regulation of chromosome healing.

PMID- 21945096
TI  - SOD2-mediated adaptive responses induced by low-dose ionizing radiation via TNF
      signaling and amifostine.
AB  - Manganese superoxide dismutase (SOD2)-mediated adaptive processes that protect
      against radiation-induced micronucleus formation can be induced in cells after a
      2-Gy exposure by previously exposing them to either low-dose ionizing radiation
      (10cGy) or WR1065 (40MUM), the active thiol form of amifostine. Although both
      adaptive processes culminate in elevated levels of SOD2 enzymatic activity, the
      underlying pathways differ in complexity, with the tumor necrosis factor alpha
      (TNFalpha) signaling pathway implicated in the low-dose radiation-induced
      response, but not in the thiol-induced pathway. The goal of this study was the
      characterization of the effects of TNFalpha receptors 1 and 2 (TNFR1, TNFR2) on
      the adaptive responses induced by low-dose irradiation or thiol exposure using
      micronucleus formation as an endpoint. BFS-1 wild-type cells with functional
      TNFR1 and 2 were exposed 24h before a 2-Gy dose of ionizing radiation to either
      10cGy or a 40MUM dose of WR1065. BFS2C-SH02 cells, defective in TNFR1, and BFS2C
      SH22 cells, defective in both TNFR1 and TNFR2 and generated from BFS2C-SH02 cells
      by transfection with a murine TNFR2-targeting vector and confirmed to be TNFR2
      defective by quantitative PCR, were also exposed under similar conditions for
      comparison. A 10-cGy dose of radiation induced a significant elevation in SOD2
      activity in BFS-1 (P<0.001) and BFS2C-SH02 (P=0.005) but not BFS2C-SH22 cells
      (P=0.433), compared to their respective untreated controls. In contrast, WR1065
      significantly induced elevations in SOD2 activity in all three cell lines
      (P=0.001, P=0.007, P=0.020, respectively). A significant reduction in the
      frequency of radiation-induced micronuclei was observed in each cell line when
      exposure to a 2-Gy challenge dose of radiation occurred during the period of
      maximal elevation in SOD2 activity. However, this adaptive effect was completely
      inhibited if the cells were transfected 24h before low-dose radiation or thiol
      exposure with SOD2 siRNA. Under the conditions tested, TNFR1 and 2 inhibition
      negatively affected the low-dose radiation-induced but not the thiol-induced
      adaptive responses observed to be mediated by elevations in SOD2 activity.

PMID- 21945097
TI  - Physical and chemical modulation of lipid rafts by a dietary n-3 polyunsaturated
      fatty acid increases ethanol-induced oxidative stress.
AB  - Dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) have been reported to
      modulate lipid raft-dependent signaling, but not yet lipid raft-dependent
      oxidative stress. Previously, we have shown that ethanol-induced membrane
      remodeling, i.e., an increase in membrane fluidity and alterations in physical
      and biochemical properties of lipid rafts, participated in the development of
      oxidative stress. Thus, we decided to study n-3 PUFA effects in this context, by
      pretreating hepatocytes with eicosapentaenoic acid (EPA), a long-chain n-3 PUFA,
      before addition of ethanol. EPA was found to increase ethanol-induced oxidative
      stress through membrane remodeling. Addition of EPA resulted in a marked increase
      in lipid raft aggregation compared to ethanol alone. In addition, membrane
      fluidity of lipid rafts was markedly enhanced. Interestingly, EPA was found to
      preferentially incorporate into nonraft membrane regions, leading to raft
      cholesterol increase. Lipid raft aggregation by EPA enhanced phospholipase Cgamma
      translocation into these microdomains. Finally, phospholipase Cgamma was shown to
      participate in the potentiation of oxidative stress by promoting lysosome
      accumulation, a major source of low-molecular-weight iron. To conclude, the
      ability of EPA to modify lipid raft physical and chemical properties plays a key
      role in the enhancement, by this dietary n-3 PUFA, of ethanol-induced oxidative
      stress.

PMID- 21945098
TI  - Differentiation of SH-SY5Y cells to a neuronal phenotype changes cellular
      bioenergetics and the response to oxidative stress.
AB  - Cell differentiation is associated with changes in metabolism and function.
      Understanding these changes during differentiation is important in the context of
      stem cell research, cancer, and neurodegenerative diseases. An early event in
      neurodegenerative diseases is the alteration of mitochondrial function and
      increased oxidative stress. Studies using both undifferentiated and
      differentiated SH-SY5Y neuroblastoma cells have shown distinct responses to
      cellular stressors; however, the mechanisms remain unclear. We hypothesized that
      because the regulation of glycolysis and oxidative phosphorylation is modulated
      during cellular differentiation, this would change bioenergetic function and the
      response to oxidative stress. To test this, we used retinoic acid (RA) to induce
      differentiation of SH-SY5Y cells and assessed changes in cellular bioenergetics
      using extracellular flux analysis. After exposure to RA, the SH-SY5Y cells had an
      increased mitochondrial membrane potential, without changing mitochondrial
      number. Differentiated cells exhibited greater stimulation of mitochondrial
      respiration with uncoupling and an increased bioenergetic reserve capacity. The
      increased reserve capacity in the differentiated cells was suppressed by the
      inhibitor of glycolysis 2-deoxy-d-glucose. Furthermore, we found that
      differentiated cells were substantially more resistant to cytotoxicity and
      mitochondrial dysfunction induced by the reactive lipid species 4-hydroxynonenal
      or the reactive oxygen species generator 2,3-dimethoxy-1,4-naphthoquinone. We
      then analyzed the levels of selected mitochondrial proteins and found an increase
      in complex IV subunits, which we propose contributes to the increase in reserve
      capacity in the differentiated cells. Furthermore, we found an increase in MnSOD
      that could, at least in part, account for the increased resistance to oxidative
      stress. Our findings suggest that profound changes in mitochondrial metabolism
      and antioxidant defenses occur upon differentiation of neuroblastoma cells to a
      neuron-like phenotype.

PMID- 21945101
TI  - Role of antigens and virulence factors of Salmonella enterica serovar Typhi in
      its pathogenesis.
AB  - Salmonella enterica serovar Typhi (S. Typhi), the aetiologic agent of typhoid
      fever, is a human restricted pathogen. The molecular mechanism of Salmonella
      pathogenicity is complex. The investigations of the molecular mechanisms of
      Salmonella virulence factors have shown that pathogenic Salmonella spp. are
      distinguished from their non-pathogenic relatives by the presence of specific
      pathogenicity genes, often organized in so-called pathogenicity islands (PIs).
      The type III secretion system (T3SS) proteins encoded by two Salmonella PIs
      (SPIs) are associated with the pathogenicity at molecular level. The
      identification of T3SS has provided new insight into the molecular factors and
      mechanisms underlying bacterial pathogenesis. The T3SS encoded by SPI-1 contains
      invasion genes; while SPI-2 is responsible for intracellular pathogenesis and has
      a crucial role for systemic S. enterica infections. These studies reveal a
      complex set of pathogenic interferences between intracellular Salmonella and its
      host cells. The understanding of the mechanisms by which Salmonella evade the
      host defense system and establish pathogenesis will be important for proper
      disease management.

PMID- 21945100
TI  - Choice of tumour markers in patients with neuroendocrine tumours is dependent on
      the histological grade. A marker study of Chromogranin A, Neuron specific
      enolase, Progastrin-releasing peptide and cytokeratin fragments.
AB  - BACKGROUND: Chromogranin A (CgA) is the most important tumour marker for well
      differentiated neuroendocrine tumours (NET) and neuron specific enolase (NSE) for
      poorly differentiated neuroendocrine carcinoma (NEC). This study investigated
      whether the markers progastrin-releasing peptide (proGRP) and cytokeratin
      fragments (CKfr) CK8, CK18 and CK19 (MonoTotal) can be of additional value to the
      histological classification and help predict survival in these patients. METHODS:
      CgA, NSE, proGRP and CKfr were measured in 242 patients with grade 1 NET (G1NET),
      38 with grade 2 NET (G2NET), 42 with large cell NEC (LCNEC), 251 with small cell
      NEC (SCNEC) and in 282 healthy persons. Results were compared with tumour
      characteristics and survival by means of Receiver Operating Characteristics (ROC)
      curves and Cox regression analyses. RESULTS: The largest area under the ROC curve
      was for CgA (0.86, 0.91 and 0.90, respectively) when comparing patients with
      G1NET, G2NET and LCNEC with healthy persons. ProGRP showed the highest
      sensitivity (73%) at 95% specificity in patients with SCNEC. In a multivariate
      survival analysis, only CKfr was associated with survival (P<0.0001) for patients
      with well-differentiated NET (G1NET and G2NET). For patients with poorly
      differentiated NEC, both CKfr and NSE were associated with survival (P<0.0001 and
      P=0.003, respectively). CONCLUSION: Within all histological groups a combination
      of tumour markers proved to be more informative as diagnostic and prognostic
      marker than each marker alone. In patients with well-differentiated NET and LCNEC
      we recommend the use of CgA and CKfr, whilst in patients with SCNEC, proGRP and
      CKfr are preferred.

PMID- 21945099
TI  - Can early implementation of salvage radiotherapy for prostate cancer improve the
      therapeutic ratio? A systematic review and regression meta-analysis with
      radiobiological modelling.
AB  - PURPOSE: For prostate cancer that is thought to be locally recurrent after
      prostatectomy, the optimal timing, dose and techniques for salvage radiotherapy
      (SRT) have not been established. Here we perform a systematic review of published
      reports including regression meta-analysis and radiobiologic modelling to
      identify predictors of biochemical disease control and late toxicity. METHODS: We
      performed a review of published series reporting treatment outcomes following
      SRT. Studies with at least 30 patients, median PSA before SRT of less than 2.0
      ng/mL, and median follow-up of greater than 36 months were identified. Univariate
      and multivariate analyses were performed to test Gleason Score, SRT dose, SRT
      timing, pre-SRT PSA, whole pelvic irradiation and androgen deprivation therapy as
      predictors of 5-year biochemical progression-free survival (bPFS) and severe
      (grade>=3) late GI and GU toxicity. bPFS and toxicity data were fit to tumour
      control probability and normal tissue complication probability models,
      respectively. RESULTS: Twenty-five articles met the inclusion criteria for this
      analysis. Five-year bPFS ranged from 25% to 70%. Severe late GI toxicity rates
      were 0% to 9%, and severe late GU toxicity rates were 1-11%. On multivariate
      analysis, bPFS increased with SRT dose by 2.5% per Gy and decreased with pre-SRT
      PSA by 18.3% per ng/mL (p<0.001). Late GI and GU toxicity increased with SRT dose
      by 1.2% per Gy (p=0.012) and 0.7% per Gy (p=0.010), respectively. Radiobiological
      models demonstrate the interaction between pre-SRT PSA, SRT dose and bPFS. For
      example, an increase in pre-SRT PSA from 0.4 to 1.0 ng/mL increases the SRT dose
      required to achieve a 50% bPFS rate from 60 to 70Gy. This could increase the rate
      of severe late toxicity by approximately 10%. CONCLUSION: Biochemical control
      rates following SRT increase with SRT dose and decrease with pre-SRT PSA. Severe
      late GI and GU toxicity rates also increase with SRT dose. Radiobiological models
      suggest that the therapeutic ratio of SRT may be improved by initiating treatment
      at low PSA levels.

PMID- 21945102
TI  - Polyhydroxyalkanoate production by antarctic soil bacteria isolated from Casey
      Station and Signy Island.
AB  - Polyhydroxyalkanoate (PHA) is a family of biopolymers produced by some bacteria
      and is accumulated intracellularly as carbon and energy storage material. Fifteen
      PHA-producing bacterial strains were identified from bacteria isolated from
      Antarctic soils collected around Casey Station (66 degrees 17'S, 110 degrees
      32'E) and Signy Island (60 degrees 45'S, 45 degrees 36'W). Screening for PHA
      production was carried out by incubating the isolates in PHA production medium
      supplemented with 0.5% (w/v) sodium octanoate or glucose. 16S rRNA gene sequence
      analysis revealed that the isolated PHA-producing strains were mainly Pseudomonas
      spp. and a few were Janthinobacterium spp. All the isolated Pseudomonas strains
      were able to produce medium-chain-length (mcl) PHA using fatty acids as carbon
      source, while some could also produce mcl-PHA by using glucose. The
      Janthinobacterium strains could only utilize glucose to produce
      polyhydroxybutyrate (PHB). A Pseudomonas isolate, UMAB-40, accumulated PHA up to
      48% cell dry mass when utilizing fatty acids as carbon source. This high
      accumulation occurred at between 5 degrees C and 20 degrees C, then decreased
      with increasing temperatures. Highly unsaturated mcl-PHA was produced by UMAB-40
      from glucose. Such characteristics may be associated with the ability of UMAB-40
      to survive in the cold.

PMID- 21945103
TI  - Relation between maternal thrombophilia and stillbirth according to
      causes/associated conditions of death.
AB  - OBJECTIVE: To investigate maternal thrombophilia in cases of Stillbirth (SB),
      also an uncertain topic because most case series were not characterised for
      cause/associated conditions of death. STUDY DESIGN: In a consecutive,
      prospective, multicentre design, maternal DNA was obtained in 171 cases of
      antenatal SB and 326 controls (uneventful pregnancy at term, 1:2 ratio).
      Diagnostic work-up of SB included obstetric history, neonatologist inspection,
      placenta histology, autopsy, microbiology/chromosome evaluations. Results audited
      in each centre were classified by two of us by using CoDAC. Cases were subdivided
      into explained SB where a cause of death was identified and although no defined
      cause was detected in the remnants, 64 cases found conditions associated with
      placenta-vascular disorders (including preeclampsia, growth restriction and
      placenta abruption - PVD). In the remnant 79 cases, no cause of death or
      associated condition was found. Antithrombin activity, Factor V Leiden, G20210A
      Prothrombin mutation (FII mutation) and acquired thrombophilia were analysed.
      RESULTS: Overall, the presence of a thrombophilic defect was significantly more
      prevalent in mothers with SBs compared to controls. In particular, SB mothers
      showed an increased risk of carrying Factor II mutation (OR=3.2, 95% CI: 1.3-8.3,
      p=0.01), namely in unexplained cases. Such mutation was significantly associated
      also with previous SB (OR=8.9, 95%CI 1.2-70.5). At multiple logistic regression,
      Factor II mutation was the only significantly associated variable with SB (adj
      OR=3.8, 95% CI: 1.3-13.5). CONCLUSION: These data suggest that Factor II mutation
      is the only condition specifically associated with unexplained SB and could
      represents a risk of recurrence. PVD-associated condition is unrelated to
      thrombophilia.

PMID- 21945104
TI  - Basal peroxisome proliferator activated receptor gamma coactivator 1alpha
      expression is independent of calcineurin in skeletal muscle.
AB  - Both calcineurin-A and peroxisome proliferator activated receptor gamma
      coactivator 1alpha (PGC-1alpha) are key players in the acquisition and
      maintenance of slow-oxidative skeletal muscle phenotype. Whether calcineurin can
      control PGC-1alpha expression has been proposed but is still controversial. Our
      aim was to examine the relationship between calcineurin activation and PGC-1alpha
      expression in nonexercising skeletal muscles of rats. We first examined PGC
      1alpha and modulatory calcineurin-interacting protein-1 messenger RNA (mRNA) (a
      marker of calcineurin activity) expression patterns within rat single myofibers,
      classified according to their phenotype (type I, IIa, IIx, and IIb). Secondly, we
      measured PGC-1alpha mRNA and protein in soleus and plantaris muscles of rats
      treated or not by cyclosporin A or FK506, 2 pharmacological inhibitors of
      calcineurin activity. In single myofibers, no differences were found in PGC
      1alpha mRNA levels, whereas modulatory calcineurin-interacting protein-1 mRNA was
      substantially higher in type I and IIa compared with type IIx and IIb fibers. In
      cyclosporin A- and FK506-treated animals, no decrease in PGC-1alpha mRNA and
      protein was found, despite an efficient blockade of calcineurin activity. Taken
      together, our results show that, in weight-bearing skeletal muscles, basal PGC
      1alpha expression, necessary to maintain slow-oxidative phenotype, is independent
      of calcineurin activity.

PMID- 21945105
TI  - Postprandial lipoprotein metabolism in familial hypercholesterolemia: thinking
      outside the box.
AB  - Familial hypercholesterolemia (FH) is a dominantly inherited disorder principally
      due to mutations in the low-density lipoprotein (LDL) receptor that classically
      cause markedly elevated plasma LDL cholesterol concentrations and premature
      coronary heart disease (CHD). However, elevated plasma LDL cholesterol alone does
      not fully account for the increase or variation in risk of CHD. We propose a
      hypothetical model for the role of postprandial dyslipoproteinemia based on the
      overproduction and decreased catabolism of triglyceride-rich lipoproteins, which
      may be a consequence of LDL receptor deficiency. Expression of postprandial
      dyslipoproteinemia in FH may also depend on the type of pathogenic gene variants
      and on coexistent conditions, particularly obesity and insulin resistance.
      Further research is required to investigate our model proposed and to test
      whether treating postprandial dyslipoproteinemia decreases CHD risk in FH
      incremental to standard therapy.

PMID- 21945106
TI  - Resveratrol improves insulin signaling in a tissue-specific manner under insulin
      resistant conditions only: in vitro and in vivo experiments in rodents.
AB  - Resveratrol (RSV) has various metabolic effects, especially with relatively high
      dose therapy. However, the ability of RSV to modulate insulin signaling has not
      been completely evaluated. Here, we determined whether RSV alters insulin
      signaling in insulin-responsive cells and tissues. The effects of RSV on insulin
      signaling in 3T3-L1 adipocytes under both insulin-sensitive and insulin-resistant
      states and in insulin-sensitive tissues of high fat-fed diet-induced obese (DIO)
      mice were investigated. Insulin-stimulated insulin receptor substrate-1 tyrosine
      phosphorylation (Y612) was suppressed in RSV-treated adipocytes compared with
      untreated adipocytes, as was the insulin-stimulated Akt phosphorylation (Ser473).
      However, under an insulin-resistant condition that was made by incubating 3T3-L1
      adipocytes in the conditioned medium from lipopolysaccharide-stimulated LAW264.7
      cells, RSV reduced inducible nitric oxide synthase expression and IkappaBalpha
      protein degradation and improved insulin-stimulated Akt phosphorylation (Ser473).
      In DIO mice, relatively low-dose RSV (30 mg/kg daily for 2 weeks) therapy lowered
      fasting blood glucose level and serum insulin, increased hepatic glycogen
      content, and ameliorated fatty liver without change in body weight. The insulin
      stimulated Akt phosphorylation was decreased in the liver and white adipose
      tissue of DIO mice, but it was completely normalized by RSV treatment. However,
      in the skeletal muscle of DIO mice, insulin signaling was not improved by RSV
      treatment, whereas the phosphorylation of adenosine monophosphate-activated
      protein kinase alpha (Thr172) was improved by it. Our results show that RSV
      enhances insulin action only under insulin-resistant conditions and suggest that
      the effect of RSV may depend on the type of tissue being targeted and its
      metabolic status.

PMID- 21945107
TI  - Whole-pelvis or bladder-only chemoradiation for lymph node-negative invasive
      bladder cancer: single-institution experience.
AB  - PURPOSE: Whole-pelvis (WP) concurrent chemoradiation (CCRT) is the standard
      bladder preserving option for patients with invasive bladder cancer. The standard
      practice is to treat elective pelvic lymph nodes, so our aim was to evaluate
      whether bladder-only (BO) CCRT leads to results similar to those obtained by
      standard WP-CCRT. METHODS AND MATERIALS: Patient eligibility included
      histopathologically proven muscle-invasive bladder cancer, lymph nodes negative
      (T2-T4, N-) by radiology, and maximal transurethral resection of bladder tumor
      with normal hematologic, renal, and liver functions. Between March 2005 and May
      2006, 230 patients were accrued. Patients were randomly assigned to WP-CCRT (120
      patients) and BO-CCRT (110 patients). Data regarding the toxicity profile,
      compliance, initial complete response rates at 3 months, and occurrence of
      locoregional or distant failure were recorded. RESULTS: With a median follow-up
      time of 5 years (range, 3-6), WP-CCRT was associated with a 5-year disease-free
      survival of 47.1% compared with 46.9% in patients treated with BO-CCRT (p = 0.5).
      The bladder preservation rates were 58.9% and 57.1% in WP-CCRT and BO-CCRT,
      respectively (p = 0.8), and the 5-year overall survival rates were 52.9% for WP
      CCRT and 51% for BO-CCRT (p = 0.8). CONCLUSION: BO-CCRT showed similar rates of
      bladder preservation, disease-free survival, and overall survival rates as those
      of WP-CCRT. Smaller field sizes including bladder with 2-cm margins can be used
      as bladder preservation protocol for patients with muscle-invasive lymph node
      negative bladder cancer to minimize the side effects of CCRT.

PMID- 21945108
TI  - Breast cancer-related arm lymphedema: incidence rates, diagnostic techniques,
      optimal management and risk reduction strategies.
AB  - As more women survive breast cancer, long-term toxicities affecting their quality
      of life, such as lymphedema (LE) of the arm, gain importance. Although numerous
      studies have attempted to determine incidence rates, identify optimal diagnostic
      tests, enumerate efficacious treatment strategies and outline risk reduction
      guidelines for breast cancer-related lymphedema (BCRL), few groups have
      consistently agreed on any of these issues. As a result, standardized
      recommendations are still lacking. This review will summarize the latest data
      addressing all of these concerns in order to provide patients and health care
      providers with optimal, contemporary recommendations. Published incidence rates
      for BCRL vary substantially with a range of 2-65% based on surgical technique,
      axillary sampling method, radiation therapy fields treated, and the use of
      chemotherapy. Newer clinical assessment tools can potentially identify BCRL in
      patients with subclinical disease with prospective data suggesting that early
      diagnosis and management with noninvasive therapy can lead to excellent outcomes.
      Multiple therapies exist with treatments defined by the severity of BCRL present.
      Currently, the standard of care for BCRL in patients with significant LE is
      complex decongestive physiotherapy (CDP). Contemporary data also suggest that a
      multidisciplinary approach to the management of BCRL should begin prior to
      definitive treatment for breast cancer employing patient-specific surgical,
      radiation therapy, and chemotherapy paradigms that limit risks. Further,
      prospective clinical assessments before and after treatment should be employed to
      diagnose subclinical disease. In those patients who require aggressive
      locoregional management, prophylactic therapies and the use of CDP can help
      reduce the long-term sequelae of BCRL.

PMID- 21945109
TI  - Radiogenic side effects after hypofractionated stereotactic photon radiotherapy
      of choroidal melanoma in 212 patients treated between 1997 and 2007.
AB  - PURPOSE: To evaluate side effects of hypofractionated stereotactic photon
      radiotherapy for patients with choroidal melanoma. PATIENTS AND METHODS: Two
      hundred and twelve patients with choroidal melanoma unsuitable for ruthenium-106
      brachytherapy or local resection were treated stereotactically at the Medical
      University of Vienna between 1997 and 2007 with a Linac with 6-MV photon beams in
      five fractions with 10, 12, or 14 Gy per fraction. Examinations for radiogenic
      side effects were performed at baseline and every 3 months in the first 2 years,
      then every 6 months until 5 years and then once a year thereafter until 10 years
      after radiotherapy. Adverse side effects were assessed using slit-lamp
      examination, funduscopy, gonioscopy, tonometry, and, if necessary, fundus
      photography and fluorescein angiography. Evaluations of incidence of side effects
      are based on an actuarial analysis. RESULTS: One hundred and eighty-nine (89.2%)
      and 168 (79.2%) of the tumors were within 3 mm of the macula and the optic disc,
      respectively. The five most common radiotherapy side effects were retinopathy and
      optic neuropathy (114 cases and 107 cases, respectively), cataract development
      (87 cases), neovascular glaucoma (46 cases), and corneal epithelium defects (41
      cases). In total, 33.6%, 38.5%, 51.2%, 75.5%, and 77.6% of the patients were free
      of any radiation retinopathy, optic neuropathy, cataract, neovascular glaucoma,
      or corneal epithelium defects 5 years after radiotherapy, respectively.
      CONCLUSION: In centrally located choroidal melanoma hypofractionated stereotactic
      photon radiotherapy shows a low to moderate rate of adverse long-term side
      effects comparable with those after proton beam radiotherapy. Future
      fractionation schemes should seek to further reduce adverse side effects rate
      while maintaining excellent local tumor control.

PMID- 21945110
TI  - Clinical evaluation of a robotic 6-degree of freedom treatment couch for
      frameless radiosurgery.
AB  - PURPOSE: To evaluate the added value of 6-degree of freedom (DOF) patient
      positioning with a robotic couch compared with 4DOF positioning for intracranial
      lesions and to estimate the immobilization characteristics of the BrainLAB
      frameless mask (BrainLAB AG, Feldkirchen, Germany), more specifically, the setup
      errors and intrafraction motion. METHODS AND MATERIALS: We enrolled 40 patients
      with 66 brain metastases treated with frameless stereotactic radiosurgery and a
      6DOF robotic couch. Patient positioning was performed with the BrainLAB ExacTrac
      stereoscopic X-ray system. Positioning results were collected before and after
      treatment to assess patient setup error and intrafraction motion. Existing
      treatment planning data were loaded and simulated for 4DOF positioning and
      compared with the 6DOF positioning. The clinical relevance was analyzed by means
      of the Paddick conformity index and the ratio of prescribed isodose volume
      covered with 4DOF to that obtained with the 6DOF positioning. RESULTS: The mean
      three-dimensional setup error before 6DOF correction was 1.91 mm (SD, 1.25 mm).
      The rotational errors were larger in the longitudinal (mean, 0.23 degrees ; SD,
      0.82 degrees ) direction compared with the lateral (mean, -0.09 degrees ; SD,
      0.72 degrees ) and vertical (mean, -0.10 degrees ; SD, 1.03 degrees ) directions
      (p < 0.05). The mean three-dimensional intrafraction shift was 0.58 mm (SD, 0.42
      mm). The mean intrafractional rotational errors were comparable for the vertical,
      longitudinal, and lateral directions: 0.01 degrees  (SD, 0.35 degrees ), 0.03
      degrees  (SD, 0.31 degrees ), and -0.03 degrees  (SD, 0.33 degrees ),
      respectively. The mean conformity index decreased from 0.68 (SD, 0.08) (6DOF) to
      0.59 (SD, 0.12) (4DOF) (p < 0.05). A loss of prescribed isodose coverage of 5%
      (SD, 0.08) was found with the 4DOF positioning (p < 0.05). Half a degree for
      longitudinal and lateral rotations can be identified as a threshold for coverage
      loss. CONCLUSIONS: With a mask immobilization, patient setup error and
      intrafraction motions need to be evaluated and corrected for. The 6DOF patient
      positioning with a 6DOF robotic couch to correct translational and rotational
      setup errors improves target positioning with respect to treatment isocenter,
      which is in direct relation with the clinical outcome, compared with the 4DOF
      positioning.

PMID- 21945111
TI  - [HIV prevention using pre-exposure prophylaxis].

PMID- 21945112
TI  - Metabolic changes associated with acid-base regulation during hypercarbia in the
      CO2-tolerant chondrostean, white sturgeon (Acipenser transmontanus).
AB  - CO(2) tolerance in white sturgeon is associated with the ability to tightly
      regulate intracellular pH (pHi) despite a large reduction in extracellular pH
      (pHe) termed preferential pHi regulation. How this regulatory response affects
      whole animal metabolic rate is unknown. Accordingly, we characterized oxygen
      consumption rate ( [Formula: see text] ) and metabolically-relevant organismal
      and cellular responses in white sturgeon during exposure to hypercarbia. White
      sturgeon were able to protect intracellular pH (pHi) in liver and white muscle as
      early as 6h (the earliest time period investigated) following exposure to severe
      (sub-lethal) hypercarbia (45 and 90 mm Hg PCO(2)). Sturgeon exposed to 15 and 30
      mm Hg PCO(2) exhibited pHe compensation and significant increases in [Formula:
      see text] (up to 80% greater than control values). In contrast, severe
      hypercarbia (>=45 mm Hg PCO(2)) elicited an uncompensated reduction in pHe (up to
      ~1.0 pH units) and red blood cells (as great as ~0.5 pH units), and was
      accompanied by 30 and 60% reductions in [Formula: see text] , respectively. While
      behavioral, respiratory and cellular responses to hypercarbia were observed, none
      corresponded well with the pattern or magnitude of changes in [Formula: see text]
      . The findings of this research provide empirical support for the hypothesis that
      preferential pHi regulation is not metabolically costly, and thus may have been a
      strategy strongly selected for in fishes encountering short-term hypercarbia.

PMID- 21945113
TI  - Vancomycin-resistant Enterococcus faecium outbreak caused by patient transfer in
      2 separate intensive care units.
AB  - This report describes an outbreak involving vancomycin-resistant Enterococcus
      faecium colonization in 2 separate intensive care units (ICUs). Outbreak
      investigation including pulsed-field gel electrophoresis demonstrated that
      transfer of a vancomycin-resistant Enterococcus faecium colonized patient between
      ICUs contributed to the outbreaks that occurred simultaneously in 2 separate
      ICUs.

PMID- 21945114
TI  - An alternative methodology for interpretation and reporting of hand hygiene
      compliance data.
AB  - BACKGROUND: Since 2009, all hospitals in Ontario have been mandated to publicly
      report health care provider compliance with hand hygiene opportunities
      (http://www.health.gov.on.ca/patient_safety/index.html). Hand hygiene compliance
      (HHC) is reported for 2 of the 4 moments during the health care provider-patient
      encounter. This study analyzes the HHC data by using an alternative methodology
      for interpretation and reporting. METHODS: Annualized HHC data were available for
      fiscal years 2009 and 2010 for each of the 5 hospital corporations (6 sites) in
      the North Simcoe Muskoka Local Health Integration Network. The weighted average
      for HHC was used to estimate the overall observed rate for HHC for each hospital
      and reporting period. Using Bayes' probability theorem, this estimate was used to
      predict the probability that any patient would experience HHC for at least 75% of
      hand hygiene moments. This probability was categorized as excellent (>=75%),
      above average (50%-74%), below average (25%-49%), or poor (<25%). The results
      were reported using a balanced scorecard display. RESULTS: The overall observed
      rates for HHC ranged from 50% to 87% (mean, 75% +/- 11%, P = .079). Using the
      alternative methodology for reporting, 6 of the 12 reporting periods would be
      categorized as excellent, 1 as above average, 2 as below average, and 3 as poor.
      CONCLUSION: Population-level HHC data can be converted to patient-level risk
      information. Reporting this information to the public may increase the value and
      understandability of this patient safety indicator.

PMID- 21945115
TI  - Caring behaviors perceived by elderly residents of long-term care facilities:
      scale development and psychometric assessment.
AB  - BACKGROUND: To meet the growing need for relationship-centered nursing practice
      and for nursing school accreditation in Taiwan, nursing school curricula must
      include training in care for elderly populations in institutional settings.
      However, educators lack tools for evaluating student performance in such
      settings. The few tools currently available for measuring the caring in nurses
      perceived by elderly residents of long-term care facilities (LTCFs) are either
      inappropriate for education purposes or are culturally inappropriate for elderly
      populations in Taiwan. OBJECTIVES: To develop a scale for measuring the caring
      behaviors of caregivers or student volunteers as perceived by a Taiwanese
      population of elderly residents of LTCFs and to establish the psychometric
      characteristics of the scale. METHODS: This study was conducted in two phases. In
      Phase 1, the researchers comprehensively reviewed the literature on caring. Based
      on the review, an Elderly Resident-Perceived Caring Scale (EPCS) was developed to
      measure the caring behaviors perceived by LTCF residents. To establish content
      and face validity, the items on the scale were reviewed by six experts in two
      rounds of Delphi study and by four elderly laypersons. In Phase 2, a convenience
      sample of 297 elderly residents from 18 representative elderly care facilities
      (i.e., skilled nursing facilities, independent living facilities, and assisted
      living facilities) in Taiwan were recruited to test the construct validity and
      reliability of the EPCS. RESULTS: The 14-item, 2-dimension questionnaire
      developed in this study explained 64.33% of the variance in caring perceived by
      the residents. Factor I, Comforting, included 11 items. Factor II, Encouraging,
      included 3 items. Cronbach's alpha values were .924 for the total scale and .930
      and .844 for the Comforting and Encouraging, respectively. CONCLUSION: The
      psychometric qualities of the EPCS were supported. However, further testing of
      the scale is needed to confirm its psychometric properties in a larger sample.

PMID- 21945116
TI  - Hotspot-centric de novo design of protein binders.
AB  - Protein-protein interactions play critical roles in biology, and computational
      design of interactions could be useful in a range of applications. We describe in
      detail a general approach to de novo design of protein interactions based on
      computed, energetically optimized interaction hotspots, which was recently used
      to produce high-affinity binders of influenza hemagglutinin. We present several
      alternative approaches to identify and build the key hotspot interactions within
      both core secondary structural elements and variable loop regions and evaluate
      the method's performance in natural-interface recapitulation. We show that the
      method generates binding surfaces that are more conformationally restricted than
      previous design methods, reducing opportunities for off-target interactions.

PMID- 21945117
TI  - Expression and immunolocalization of 20beta-hydroxysteroid dehydrogenase during
      testicular cycle and after hCG induction, in vivo in the catfish, Clarias
      gariepinus.
AB  - The maturation inducing hormone, 17alpha,20beta-dihydroxy-4-pregnen-3-one
      (17alpha,20beta-DP) is required for the meiotic maturation and is produced from
      the precursor 17alpha-hydroxyprogesterone by the enzyme 20beta-hydroxysteroid
      dehydrogenase (20beta-HSD) in several teleosts. Central role of 20beta-HSD in
      ovarian cycle and final oocyte maturation is well studied when compared to
      spermatogenesis. In the present study, we investigated the localization and
      expression of 20beta-HSD in testicular cycle and gonadotropin induced sperm
      maturation. During testicular ontogeny, 20beta-HSD expression was detectable at
      50 and 100 days post-hatch (dph), while the expression was high at 150 dph. In
      testicular cycle, highest levels of mRNA and protein of 20beta-HSD were observed
      during spawning phase. Intraperitoneal injection of human chorionic gonadotropin
      (hCG) to prespawning catfish elevated both 20beta-HSD transcripts and protein
      levels when compared to saline treated controls in a time-dependent manner. Serum
      17alpha,20beta-DP levels, measured during different phases of testicular cycle as
      well as following the treatment of hCG, showed a positive correlation with the
      expression of 20beta-HSD. Immunolocalization revealed the presence of 20beta-HSD
      protein predominantly in interstitial cells and spermatogonia/spermatocytes while
      20beta-HSD was undetectable in haploid cells (spermatids/sperm). These results
      together with high expression during spawning phase of testicular cycle and after
      hCG treatment in the prespawning catfish suggests a pivotal role for 20beta-HSD
      during testicular recrudescence leading to sperm maturation. Further studies
      using various fish models on testicular 20beta-HSD may provide interesting
      details to understand its importance in teleostean spermatogenesis.

PMID- 21945118
TI  - Urinary corticosterone responses to capture and toe-clipping in the cane toad
      (Rhinella marina) indicate that toe-clipping is a stressor for amphibians.
AB  - Toe-clipping, the removal of one or more toes, is a common method used to
      individually mark free-living animals. Whilst this method is widely used in
      studies of amphibians, the appropriateness of the method, and its potential
      detrimental effects have been the subject of debate. Here, we provide for the
      first time, evidence that toe-clipping is a stressor in a wild amphibian. We
      measured urinary corticosterone responses of male cane toads (Rhinella marina) to
      capture and handling only, and to toe-clipping under field conditions. Urinary
      testosterone concentrations and white blood cell proportions were also measured.
      Urinary corticosterone metabolite concentrations increased 6h after capture and
      handling only and remained high for 24h; corticosterone returned to baseline
      levels after 48 h and remained low at 72 h post capture and handling.
      Corticosterone concentrations in toads subjected to toe-clipping increased at 6h
      to significantly higher concentrations than after capture and handling only, then
      decreased more slowly than after capture and handling, and were still elevated
      (approximately double basal level) 72 h after toe-clipping. Testosterone did not
      change significantly after capture and handling only, whereas after toe-clipping
      testosterone decreased at 6h and remained low at 72 h. There were weak short-term
      effects of toe-clipping compared with capture and handling only on white blood
      cell proportions. We have clearly shown that toe-clipping is a distinctly
      stronger stressor than capture and handling alone. This indicates that there is
      an ethical cost of toe-clipping, and this should be considered when planning
      studies of amphibians.

PMID- 21945119
TI  - Effect of oxytocin, prolactin-releasing peptide, or corticotropin-releasing
      hormone on feeding behavior in steers.
AB  - As a preliminary step to elucidate the involvement of central neurotransmitters
      in the dip in voluntary feed intake during the perinatal period in cows, we
      investigated the effect of intracerebroventricular (ICV) administration of
      oxytocin, prolactin-releasing peptide (PrRP), or corticotropin-releasing hormone
      (CRH), the central functions of all of which undergo drastic changes during the
      perinatal period, on feed intake in steers. Thirty minutes before the onset of
      feeding, the treatment solution was injected into the third ventricle through an
      implanted cannula, and feeding-related behaviors were observed for 1 h after the
      onset of feeding. Neither ICV oxytocin (5 and 50 MUg) nor PrRP (2 and 20 nmol)
      reduced feed intake (n=6). Twenty nanomoles of bovine CRH noticeably inhibited
      feeding behavior compared with vehicle treatment (n=5, p<0.05). Fifty micrograms
      of oxytocin reduced latency to the first water access after feeding onset
      (p<0.1), which may be because of the stimulation of arginine vasopressin V1b
      receptor by the high dose of oxytocin. We conclude that CRH inhibits feeding
      behavior by its central action in this species, although this could also be an
      indirect effect due to the increased expression of abnormal behaviors caused by
      CRH. Central administration of neither oxytocin nor PrRP reduced feed intake in
      steers. Although the effects of sex steroids need to be examined, it appears that
      increased activity of oxytocin, and possibly PrRP, during the perinatal period
      does not contribute to the dip in voluntary feed intake in this species. On the
      other hand, it makes sense that suppressed central CRH activity during the
      perinatal period should act in the direction of maintaining or even increasing
      food intake to aid a steady supply of energy to the fetus or offspring. We thus
      speculate that CRH is not a prime candidate involved in the dip in voluntary feed
      intake during the perinatal period in cows.

PMID- 21945120
TI  - Caloric restriction promotes the reproductive capacity of female rats via
      modulating the level of insulin-like growth factor-1 (IGF-1).
AB  - The insulin-like growth factor-1 (IGF-1) plays an important role in the
      regulation of reproductive function. In the present study, we examined the
      effects of caloric restriction (CR) on the reproductive lifespan in rats and
      investigated the potential role of IGF-1. After 10 weeks of treatment, we
      determined the distribution of the ovarian follicles at various stages and
      measured the plasma level of IGF-1, luteinizing hormone (LH), follicle
      stimulating hormone (FSH), and estrogen (ESG). Our results show that IGF-1 level
      was decreased after CR and correlated with the decrease in the levels of LH, FSH
      and ESG. Moreover, a higher percentage of primordial follicles and surviving
      follicles was observed in CR rats than in control rats (P<0.05).
      Immunohistochemical analysis showed that IGF-1 was extensively expressed in the
      cytoplasm of granulosa cells in the surviving follicles at different stages but
      not in the atretic follicles. Taken together, these results suggest that caloric
      restriction promotes the reproductive capacity of female rats via modulating the
      level of IGF-1, which then regulate pituitary gonadotrope cells to reduce the
      release of LH, FSH and ESG, and modulate follicular development.

PMID- 21945121
TI  - TH1 and TH17 interactions in untreated inflamed mucosa of inflammatory bowel
      disease, and their potential to mediate the inflammation.
AB  - BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) have been associated
      with a T helper1 (TH1) and a TH2 cytokine profile, respectively. Recently, a TH17
      lineage has been introduced, but their role in the inflammation of CD and UC is
      not fully understood. AIM: To characterize the cytokines directing the TH17 cells
      and their interactions with TH1 cells in the mucosa of untreated patients with CD
      and UC. METHOD: Seventy-nine patients with untreated UC, 32 patients with
      untreated CD and 23 controls with no signs of colon disease were included in the
      study. Clinical indices for ulcerative colitis (UCDAI) and Crohn's disease (CDAI)
      were assessed. Biopsies for measurements of interleukin (IL)-17A, IL-23, IL-6,
      transforming growth factor-beta (TGF-beta), interferon-gamma (IFN-gamma), mRNA
      levels as well as immunohistochemical (IHC) analyses were performed. RESULTS: The
      gene expression for all cytokines in UC and for all cytokines except for TGF-beta
      in CD were significantly increased compared with the controls. The
      immunohistochemical analysis showed significantly increased number of IL-17A
      positive cells in lamina propria and epithelium of both UC and CD compared to
      controls. The levels of IL-17A and IL-23 mRNA were significantly higher in UC
      than in CD while the levels of IL-6 were significantly higher in CD compared with
      UC. The levels of IL-17A, IL-6 and IL-23 mRNA were associated with the disease
      activity score in both UC and CD. IFN-gamma was associated with the disease
      activity in UC, but did not reach significant level in CD. CONCLUSION: Increased
      levels of IL-17A and IL-23 were found in both UC and CD compared to controls.
      Association to the grade of inflammation and clinical activity was also observed.
      IL-17A and IL-23 were significantly higher in UC than in CD. TH1 and TH17
      cytokines seem to act synergistically in inflammatory bowel disease (IBD) with no
      apparent polarization between UC and CD.

PMID- 21945122
TI  - Macrophage colony stimulating factor and monocyte chemoattractant protein 2 are
      elevated in intrinsic asthmatics.
AB  - BACKGROUND: Intrinsic asthma, etiology unknown, occurs later in life, mostly in
      females. It is associated with nasal polyps and massive eosinopillic infiltration
      of the respiratory mucous membrane, aspirin intolerance and steroid dependence.
      The aim of the study was to determine the cytokine and chemokine profile in sera
      of intrinsic asthmatics and control subjects. METHODS: Blood was taken from 10
      intrinsic asthmatic female and 12 control female subjects. Expression profile of
      42 different cytokines and chemokines were measured using a microarray composed
      of antibodies against the cytokines and chemokines. Complete blood count and C
      reactive protein were measured, to assess the state of inflammation in both
      groups. RESULTS: We have identified Macrophage Colony Stimulating Factor, a
      proinflammatory cytokine and Monocyte Chemoattractant Protein 2, a CC chemokine
      as having significantly higher expression levels in intrinsic asthmatic subjects
      compared to controls (341.71+/-31.28 SEM Signal intensity) versus (247.97+/-28.09
      SEM Signal intensity), p=0.036 and (397.07+/-38.19 SEM Signal intensity) versus
      (311.33+/-28.76 SEM Signal intensity), p=0.036, respectively. There were no
      significant differences in the other cytokines and chemokines measured nor were
      there any differences in the inflammatory measurements between the two groups
      except for eosinophil counts, the hall mark of intrinsic asthma. CONCLUSION:
      Macrophage Colony Stimulating Factor and Monocyte Chemoattractant Protein are
      elevated in sera of intrinsic asthmatics compared to normal controls. These
      cytokines may have a critical role in the inflammatory pathology of intrinsic
      asthma.

PMID- 21945123
TI  - Inclusion interaction of chloramphenicol and heptakis (2,6-di-O-methyl)-beta
      cyclodextrin: phase solubility and spectroscopic methods.
AB  - The inclusion interaction between chloramphenicol and heptakis (2,6-di-O-methyl)
      beta-cyclodextrin (DMBCD) had been investigated by phase solubility and
      spectroscopic methods such as UV-vis spectroscopy, circular dichroism, Fourier
      transform infrared (FT-IR) spectroscopy, proton nuclear magnetic resonance
      spectroscopy ((1)H NMR) as well as 2D-ROESY spectra. Phase solubility analysis
      showed A(L)-type diagram with DMBCD, which suggested the formation of 1:1
      inclusion complex of DMBCD with chloramphenicol. The estimated stability constant
      (K(s)) of the inclusion complex of chloramphenicol with DMBCD is 493 M(-1) at 293
      K. The solubility enhancement of chloramphenicol in the presence of DMBCD is
      stronger than that in the presence of beta-CD, HP-beta-CD and M-beta-CD. The
      results obtained by spectroscopic methods showed that the nitrophenyl moiety of
      chloramphenicol is deeply inserted into inner cavity of DMBCD from the narrow rim
      of DMBCD, which the inclusion model of chloramphenicol with DMBCD differs from
      that with beta-CD.

PMID- 21945124
TI  - Complementary hydrogen bonding of a carboxylato-barbiturate with urea and
      acetamide: experimental and theoretical approach.
AB  - A barbiturate derivative, 4-(2,4,6-trioxo-tetrahydro-pyrimidine-5-ylidenemethyl)
      benzoic acid (L1) possessing functional complementarity to amides has been
      synthesized and characterized. Its binding separately with urea and acetamide was
      monitored using UV-vis, fluorescence and (1)H-NMR spectroscopic titrations.
      Experiments suggested stronger binding of L1 with urea as compared to acetamide.
      The solid adducts of L1 prepared separately with urea and acetamide were also
      characterized using IR, (1)H-NMR spectral and PXRD techniques. Theoretical
      studies on hydrogen bonded complexes of L1-urea and L1-acetamide in the gas
      phase, aqueous, and DMSO medium were carried out using density functional theory
      (DFT) at the B3LYP/6-31G** level. The theoretical calculations agreed to the
      experimental results.

PMID- 21945125
TI  - Copper and cobalt complexes of octadentate azamacrocycles: spectrophotometric
      titration, stopped-flow kinetics and crystallographic study.
AB  - Details of complex formation kinetics are reported for tetrakis(2-hydroxyethyl)
      substituted cyclen (L(1)) and cyclam (L(2)) with Cu(II) and Co(II). Stopped-flow
      kinetics and spectroscopic titration methods were employed for the activation
      parameters and stability constants, respectively. X-ray studies revealed that the
      pendant 2-hydroxyethyl groups are not equivalent: two are folded over the
      macrocycle and maintained by intramolecular hydrogen bonds while the others are
      extended and pointed away from the macrocyclic cavity. Complex formation kinetics
      and spectroscopic titration were performed in aqueous acidic buffer solutions.
      Thermodynamic and kinetic parameters revealed that the ring size of the
      macrocycles plays an extremely important role for each metal ion studied. Stopped
      flow kinetic measurements explained the mechanism of the complex formation
      process of both Cu(II) and Co(II) which proceed in outer-sphere interactions with
      ligands. There are two steps in the complex formation of the system studied. The
      initial step is a second order reaction between the metal ion and macrocycle with
      a second order rate constant.

PMID- 21945126
TI  - Spectroscopic analyses on interaction of Amantadine-Salicylaldehyde, Amantadine-5
      Chloro-Salicylaldehyde and Amantadine-o-Vanillin Schiff-Bases with bovine serum
      albumin (BSA).
AB  - In this work, three Tricyclo [3.3.1.1(3,7)] decane-1-amine (Amantadine) Schiff
      Bases, Amantadine-Salicylaldehyde (AS), Amantadine-5-Chloro-Salicylaldehyde (AS-5
      C) and Amantadine-o-Vanillin (AS-o-V), were synthesized by direct heating reflux
      method in ethanol solution and characterized by infrared spectrum and elementary
      analysis. Fluorescence quenching was used to study the interaction of these
      Amantadine Schiff-Bases (AS, AS-5-C and AS-o-V) with bovine serum albumin (BSA).
      According to fluorescence quenching calculations the bimolecular quenching
      constant (K(q)), apparent quenching constant (K(SV)), effective binding constant
      (K(A)) and corresponding dissociation constant (K(D)), binding site number (n)
      and binding distance (r) were obtained. The results show that these Amantadine
      Schiff-Bases can obviously bind to BSA molecules and the binding strength order
      is AS<AS-5-C=AS-o-V. Synchronous fluorescence spectroscopy reveals that these
      Amantadine Schiff-Bases adopt different way to bind with BSA molecules. That is,
      the AS and AS-5-C are accessibility to tryptophan (Trp) residues more than the
      tyrosine (Tyr) residues, while the AS-o-V is equally close to the Tyr and Trp
      residues.

PMID- 21945127
TI  - Analysis of binding interaction between pegylated puerarin and bovine serum
      albumin by spectroscopic methods and dynamic light scattering.
AB  - The interaction between bovine serum albumin (BSA) and pegylated puerarin (Pur)
      in aqueous solution was investigated by UV-Vis spectroscopy, fluorescence
      spectroscopy and circular dichroism spectra (CD), as well as dynamic light
      scattering (DLS). The fluorescence of BSA was strongly quenched by the binding of
      pegylated Pur to BSA. The binding constants and the number of binding sites of
      mPEG(5000)-Pur with BSA were 2.67+/-0.12 and 1.37+/-0.05 folds larger after
      pegylating, which were calculated from the data obtained from fluorescence
      quenching experiments. The enthalpy change (DeltaH) and entropy change (DeltaS)
      were calculated to be 4.09 kJ mol(-1) and 20.01 J mol(-1) K(-1), respectively,
      according to Van't Hoff equation, indicating that the hydrophobic force plays a
      main role in the binding interaction between pegylated Pur and BSA. In addition,
      the negative sign for Gibbs free energy change (DeltaG) implies that the
      interaction process is spontaneous. Moreover, the results of synchronous
      fluorescence and CD spectra demonstrated that the microenvironment and the
      secondary conformation of BSA were changed. Comparing with Pur, all our data
      collected indicated that pegylated Pur interacted with BSA in the same way as
      that of Pur, but docked into the hydrophobic pocket of BSA with more
      accessibility and stronger binding force. DLS measurements showed monomethoxy
      polyethylene glycol (mPEG) have an effect on BSA conformation, and revealed that
      changes in BSA size might be due to increases in binding constant and the
      absolute values of DeltaG after Pur pegylation.

PMID- 21945128
TI  - Antipsychotic medication and mortality: a clarification.

PMID- 21945129
TI  - HIV-mediated up-regulation of invariant chain (CD74) correlates with generalized
      immune activation in HIV+ subjects.
AB  - HIV Nef-mediated up-regulation of invariant chain (Ii chain, also CD74) is
      presumed to play an active role in HIV immunopathogenesis. However, this has not
      been definitely ascertained. In order to help elucidate this hypothesis, Ii
      chain, CD4, HLA-DR and HLA-ABC expression was analyzed ex vivo in monocyte
      derived macrophages (MDMs) from HIV(+) subjects. Viral load, CD4(+) T cell count
      and immune activation were also determined in enrolled subjects. Correlations
      between these parameters and the modulation of cell surface molecules in infected
      cells were studied. Ii chain expression was found to be up-regulated in infected
      MDMs derived from all patients but one (median fold up-regulation 2.47+/-1.82
      (range 0.87-7.36)). Moreover, the magnitude of Ii chain up-regulation
      significantly correlated with higher activation of B and CD4(+) T cells (studied
      by HLA-DR and CD38 expression). On the other hand, lower HLA-ABC (i.e. stronger
      down-regulation) in infected MDMs was associated with higher CD4 counts. No
      correlation was observed between the magnitude of Ii chain up-regulation and the
      other Nef functions studied here. This is the first study reporting that Ii chain
      up-regulation occurs on naturally infected antigen presenting cells obtained
      directly from HIV(+) subjects. Moreover, it is also shown that the magnitude of
      this up-regulation correlates with immune activation. This allows postulating an
      alternative hypothesis regarding the contribution of Ii chain up-regulation to
      HIV-mediated immune damage.

PMID- 21945130
TI  - Efficacy and safety of the seven-day buprenorphine transdermal system in opioid
      naive patients with moderate to severe chronic low back pain: an enriched,
      randomized, double-blind, placebo-controlled study.
AB  - CONTEXT: This article presents the results of a pivotal Phase 3 study that
      assesses a new treatment for the management of chronic low back pain: a
      transdermal patch containing the opioid buprenorphine. In this randomized,
      placebo-controlled study with an enriched enrollment design, the buprenorphine
      transdermal system (BTDS) was found to be efficacious and generally well
      tolerated. OBJECTIVES: This enriched, multicenter, randomized, double-blind study
      evaluated the efficacy, tolerability, and safety of BTDS in opioid-naive patients
      who had moderate to severe chronic low back pain. METHODS: Patients who tolerated
      and responded to BTDS (10 or 20 mcg/hour) during an open-label run-in period were
      randomized to continue BTDS 10 or 20 mcg/hour or receive matching placebo. The
      primary outcome was "average pain over the last 24 hours" at the end of the 12
      week double-blind phase, collected on an 11-point scale (0=no pain, 10=pain as
      bad as you can imagine). Sleep disturbance (Medical Outcomes Study subscale) and
      total number of supplemental analgesic tablets used were secondary efficacy
      variables. RESULTS: Fifty-three percent of patients receiving open-label BTDS
      (541 of 1024) were randomized to receive BTDS (n=257) or placebo (n=284).
      Patients receiving BTDS reported statistically significantly lower pain scores at
      Week 12 compared with placebo (least square mean treatment difference: -0.58,
      P=0.010). Sensitivity analyses of the primary efficacy variable and results of
      the analysis of secondary efficacy variables supported the efficacy of BTDS
      relative to placebo. During the double-blind phase, the incidence of treatment
      emergent adverse events was 55% for the BTDS treatment group and 52% for the
      placebo treatment group. Laboratory, vital sign, and electrocardiogram
      evaluations did not reveal unanticipated safety findings. CONCLUSION: BTDS was
      efficacious in the treatment of opioid-naive patients with moderate to severe
      chronic low back pain. Most treatment-emergent adverse events observed were
      consistent with those associated with the use of opioid agonists and transdermal
      patches.

PMID- 21945131
TI  - A scale for measuring feelings of support and security regarding cancer care in a
      region of Japan: a potential new endpoint of cancer care.
AB  - CONTEXT: Having a sense of security about the availability of care is important
      for cancer patients and their families. OBJECTIVES: To develop a scale for the
      general population to evaluate feelings of support and security regarding cancer
      care, and to identify factors associated with a sense of security. METHODS: A
      cross-sectional anonymous questionnaire was administered to 8000 subjects in four
      areas of Japan. Sense of security was measured using five statements and using a
      seven-point Likert scale: "If I get cancer 1) I would feel secure in receiving
      cancer treatment, 2) my pain would be well relieved, 3) medical staff will
      adequately respond to my concerns and pain, 4) I would feel secure as a variety
      of medical care services are available, and 5) I would feel secure in receiving
      care at home." We performed an exploratory factor analysis as well as uni- and
      multivariate analyses to examine factors associated with such a sense of
      security. RESULTS: The five items regarding sense of security were aggregated
      into one factor, and Cronbach's alpha was 0.91. In the Yamagata area where
      palliative care services were not available, the sense of security was
      significantly lower than in the other three regions. Female gender (P=0.035),
      older age (P<0.001), and having cancer (P<0.001) were significantly associated
      with a strong sense of security. CONCLUSION: A new scale that evaluates sense of
      security with regard to cancer care was developed. Future studies should examine
      whether establishing a regional health care system that provides quality
      palliative care could improve the sense of security of the general population.

PMID- 21945132
TI  - Heterozygous deletion of NR1 subunit of the NMDA receptor alters ethanol-related
      behaviors and regional expression of NR2 subunits in the brain.
AB  - NMDA receptors have been hypothesized to play a role in various aspects of
      ethanol-related phenotypes, notably in ethanol withdrawal. However, the role of
      each of the specific subunits remains unclear. To address this issue, mice that
      are heterozygous for the NR1 deletion, and thus have a reduction in functional
      NMDA receptors, were examined for ethanol consumption and acute ethanol
      withdrawal. Additionally, mice were examined for the level of vocalization
      following footshock, and behavior in an elevated plus maze, to determine their
      responses to stress. In these behavioral tests, NR1 heterozygous mice were shown
      to consume significantly higher levels of ethanol in the two bottle-choice test
      showing a possible role for this receptor in ethanol consumption. Analysis of
      acute withdrawal found that the heterozygous mice exhibit lower levels of
      handling-induced convulsions consistent with a role in ethanol sensitivity or
      withdrawal. In contrast, no effects on stress-related phenotypes were detected.
      Levels of NR2A-NR2D subunits of the NMDA receptor in specific brain regions were
      compared between NR1+/- mice and wild-type controls to assess whether the
      behavioral responses were specific to the diminution in NR1 expression or whether
      these changes could be due to secondary changes in expression of other NMDA
      subunits. Real-time quantitative PCR, Western blot and immunohistochemistry were
      used to examine expression levels in the hippocampus, neocortex, striatum and
      cerebellum. For the majority of the subunits, no differences were found between
      the wild-type and heterozygous mice in any of the brain regions. However, the
      NR2B subunit exhibited differences in expression of RNA in the hippocampus and
      protein levels in multiple brain regions, between wild-type and NR1+/- mice.
      These results show that NR1 plays a role, through mechanisms as yet unknown, in
      the expression of NR2 subunits in a region and subtype specific manner. This
      provides evidence of the effects of altered levels of NR1 expression on ethanol
      withdrawal and consumption, and suggests that concomitant changes in the levels
      of NR2B may contribute to that effect.

PMID- 21945134
TI  - Channel catfish leukocyte immune-type receptor mediated inhibition of cellular
      cytotoxicity is facilitated by SHP-1-dependent and -independent mechanisms.
AB  - Channel catfish (Ictalurus punctatus) leukocyte immune-type receptors (IpLITRs)
      are immunoregulatory proteins belonging to the immunoglobulin superfamily that
      likely play an important role in the regulation of teleost immune cell effector
      responses. IpLITRs are expressed by myeloid and lymphoid subsets and based on
      their structural features can be classified as either putative stimulatory or
      inhibitory forms. We have recently demonstrated at the biochemical and functional
      levels that stimulatory IpLITR-types induced intracellular signaling cascades
      resulting in immune cell activation. Alternatively, we have shown that putative
      inhibitory IpLITRs may abrogate immune cell responses by recruiting teleost Src
      homology 2 (SH2) domain-containing cytoplasmic phosphatases (SHP) to their
      tyrosine-containing cytoplasmic tails. In the present study, we used vaccinia
      virus to express recombinant chimeric proteins encoding the extracellular and
      transmembrane regions of human KIR2DL3 fused with the cytoplasmic tails of two
      putative inhibitory IpLITRs (i.e. IpLITR1.2a and IpLITR1.1b) in mouse spleen
      derived cytotoxic lymphocytes. This approach allowed us to study the specific
      effects of IpLITR-induced signaling on lymphocyte killing of B cell targets (e.g.
      721.221 cells) using a standard chromium release assay. Our results suggest that
      both IpLITR1.2a and IpLITR1.1b are potent inhibitors of lymphocyte-mediated
      cellular cytotoxicity. Furthermore, using a catalytically inactive SHP-1 mutant
      in combination with site-directed mutagenesis and co-immunoprecipitations, we
      also demonstrate that the IpLITR1.2a-mediated functional inhibitory response is
      SHP-1-dependent. Alternatively, IpLITR1.1b-mediated inhibition of cellular
      cytotoxicity is facilitated by both SHP-1-dependent and independent mechanisms,
      possibly involving the C-terminal Src kinase (Csk). The involvement of this
      inhibitory kinase requires binding to a tyrosine residue encoded in the unique
      membrane proximal cytoplasmic tail region of IpLITR1.1b. Overall, this represents
      the first functional information for inhibitory IpLITR-types and reveals that
      catfish LITRs engage SHP-dependent and -independent inhibitory signaling pathways
      to abrogate lymphocyte-mediated killing.

PMID- 21945135
TI  - Landscape distribution of Oldowan stone artifact assemblages across the fault
      compartments of the eastern Olduvai Lake Basin during early lowermost Bed II
      times.
AB  - The density and composition of Oldowan stone artifact assemblages deposited
      during the first ca. 20,000 years of lowermost Bed II times show a recurrent
      pattern of variation across recognized synsedimentary faults that
      compartmentalized landscapes of the eastern Olduvai Lake Basin. When active, the
      faults created minor topographic relief. The upthrown fault footwalls accumulated
      assemblages with relatively high densities of artifacts, including types
      retaining potential usefulness, particularly volcanic flaked pieces, manuports,
      pounded pieces, and split cobbles. Values for these assemblage characteristics
      decline toward the lower-lying hangingwall of the fault compartments, accompanied
      by an increase in the proportionate weight of artifact assemblages comprising
      quartzite, particularly flaking shatter and potentially useful detached pieces.
      Values reverse once again at faults, either on the downthrown, hangingwall side
      or on the upthrown side. The patterns are stronger for the volcanic components of
      the artifact assemblages than for the quartzite components, reflecting the
      additional influence of distance from the local source on quartzite assemblage
      characteristics reported previously. The landscape distributions of artifact
      assemblages are consistent with a landscape-fault model in which minor fault
      induced topographic relief at times created a mosaic of vegetation environments
      repeated within each of the three fault compartments of the lake margin and
      distal alluvial fan. The fault-compartmentalized landscape model is currently
      supported only by sediment thickness and facies changes across synsedimentary
      faults, but it provides predictions for spatial variation in the cover abundance
      of trees, freshwater reservoirs and associated distributions of resources and
      hazards associated with stone artifact use and discard that can be tested if
      sample sizes of key paleoenvironmental indicators are increased.

PMID- 21945133
TI  - Effects of multiple daily genistein treatments on delayed alternation and a
      differential reinforcement of low rates of responding task in middle-aged rats.
AB  - The use of extracts that are highly enriched in phytoestrogens, such as
      genistein, has become popular to promote various aspects of healthy aging,
      including maintenance of cognitive function. These compounds are promoted to
      menopausal women as safe, natural alternatives to traditional estrogen therapies,
      yet their safety and efficacy are poorly understood. Previous research in our lab
      found that once daily oral treatment of ovariectomized female Long-Evans (LE)
      rats with the soy phytoestrogen, genistein resulted in subtle deficits in
      performance on cognitive tasks assessing working memory and response
      inhibition/timing ability. The present study further modeled exposure of the
      menopausal woman to genistein by treating 14-month old ovariectomized female LE
      rats three times daily at a dose of genistein resulting in serum concentrations
      similar to those that could be achieved in humans consuming either a commercially
      available soy isoflavone supplement or a diet high in these phytoestrogens.
      Genistein (3.4 mg/kg) or sucrose control pellets were orally administered to
      animals daily, 30 min before behavioral testing, and again both 4 and 8 h after
      the first treatment. The test battery consisted of a delayed spatial alternation
      task (DSA) that tested working memory and a differential reinforcement of low
      rates of responding (DRL) task that tested inhibitory control/timing. Genistein
      treatment impaired DSA performance relative to sucrose controls. Performance on
      the DRL task was largely unaffected by genistein treatment. Although the
      impairment measured on DSA was less pronounced than that we have previously
      reported following chronic treatment with 17beta-estradiol, the pattern of the
      deficit was very similar to that observed with 17beta-estradiol.

PMID- 21945136
TI  - Allelic polymorphism in the second exon of Ovar-DRB1 in fat-tailed sheep.
AB  - Ovar-DRB1 is one of the most important response genes in the major
      histocompatibility complex (MHC) class II region of sheep. Gene polymorphism in
      the second exon of Ovar-DRB1 in three different Iranian fat-tailed sheep breeds
      (Lori-Bakhtiari, Shaul and Zandi) was analyzed by either restriction fragment
      length polymorphisms (RFLP) or direct sequencing. A total of 92 Lori-Bakhtiari,
      40 Shaul, and 47 Zandi sheep were examined. PCR-RFLP identified 17 genotypes in
      Lori-Bakhtiari sheep, 12 in Shaul sheep and 11 in Zandi sheep. Collectively, 24
      different genotypes could be found for Iranian fat-tailed sheep. Using direct
      sequencing, seven new sequences in exon 2 of the Ovar-DRB1 gene were identified.
      Generalized linear modeling with a multinomial error structure showed that the
      sheep populations had significantly different allele frequencies.

PMID- 21945137
TI  - Desmosome dynamics in migrating epithelial cells requires the actin cytoskeleton.
AB  - Re-modeling of epithelial tissues requires that the cells in the tissue rearrange
      their adhesive contacts in order to allow cells to migrate relative to
      neighboring cells. Desmosomes are prominent adhesive structures found in a
      variety of epithelial tissues that are believed to inhibit cell migration and
      invasion. Mechanisms regulating desmosome assembly and stability in migrating
      cells are largely unknown. In this study we established a cell culture model to
      examine the fate of desmosomal components during scratch wound migration.
      Desmosomes are rapidly assembled between epithelial cells at the lateral edges of
      migrating cells and structures are transported in a retrograde fashion while the
      structures become larger and mature. Desmosome assembly and dynamics in this
      system are dependent on the actin cytoskeleton prior to being associated with the
      keratin intermediate filament cytoskeleton. These studies extend our
      understanding of desmosome assembly and provide a system to examine desmosome
      assembly and dynamics during epithelial cell migration.

PMID- 21945138
TI  - Relation of ventricular premature complexes to heart failure (from the
      Atherosclerosis Risk In Communities [ARIC] Study).
AB  - Analogous to rapid ventricular pacing, frequent ventricular premature complexes
      (VPCs) can predispose over time to cardiomyopathy and subsequent heart failure
      (HF). We examined the association of frequent VPCs with HF incidence in a
      population-based cohort, free of HF and coronary heart disease at baseline. At
      study baseline (1987 to 1989), >=1 VPC on a 2-minute rhythm electrocardiographic
      strip was seen in 5.5% (739 of 13,486) of the middle-age (45 to 64 years old at
      baseline) white and black, men and women of the Atherosclerosis Risk In
      Communities cohort. Incident HF was defined as the first appearance of
      International Classification of Diseases code 428.x in the hospital discharge
      record or death certificate through 2005. During an average follow-up of 15.6
      years, incident HF was seen in 10% the participants (19.4% of those with VPCs vs
      9.4% of those without). The age-, race-, and gender-adjusted hazard ratio of HF
      for VPCs was 1.89 (95% confidence interval 1.59 to 2.24). After multivariable
      adjustment for potential confounders, the hazard ratio of HF for those with any
      VPC versus no VPC was 1.63 (95% confidence interval 1.36 to 1.96). After
      additional adjustment for incident coronary heart disease as a time-varying
      covariate, the hazard ratio was 1.71 (95% confidence interval 1.42 to 2.08).
      Those with a greater frequency of VPCs or complex VPCs had similar rates of HF
      compared to those with a single VPC and all had rates greater than those with no
      VPC. In conclusion, in this large population-based cohort, the presence of VPCs
      was associated with incident HF, independent of incident coronary heart disease.

PMID- 21945139
TI  - Effect of mild, asymptomatic obstructive sleep apnea on daytime heart rate
      variability and impedance cardiography measurements.
AB  - Dysregulation of autonomic nervous system dynamics is important in the
      pathophysiology of cardiovascular risk in obstructive sleep apnea (OSA). Heart
      rate variability (HRV) and impedance cardiography measures can estimate autonomic
      activity but have not gained traction clinically. The hypothesis of this study
      was that even in a cohort of patients with mild, asymptomatic OSA without overt
      cardiovascular disease, daytime HRV metrics and impedance cardiography
      measurements of preejection period would demonstrate increased sympathetic and
      decreased parasympathetic modulation compared to matched controls. Obese subjects
      (body mass index >=30 kg/m(2)) without any known cardiovascular or inflammatory
      co-morbidities were recruited from the community. Subjects underwent standard in
      laboratory polysomnography followed by simultaneous electrocardiographic and
      impedance cardiographic recordings while supine, supine with paced breathing, and
      after standing. Seventy-four subjects were studied, and 59% had OSA (apnea
      hypopnea index >=10 events/hour), with a median apnea-hypopnea index of 25.8
      events/hour. Subjects with OSA had significantly decreased daytime time- and
      frequency-domain HRV indexes, but not significantly different preejection
      periods, compared to controls. Apnea-hypopnea index was a significant independent
      predictor of time-domain HRV measures in all awake conditions, after controlling
      for age, gender, blood pressure, fasting cholesterol levels and glycosylated
      hemoglobin. In conclusion, these results demonstrate reductions in cardiac vagal
      modulation, as measured by multiple daytime time-domain markers of HRV, in
      patients with asymptomatic OSA compared to controls. Further prospective outcomes
      based studies are needed to evaluate the applicability of these metrics for
      noninvasive screening of obese patients with asymptomatic OSA, before the onset
      of overt cardiovascular disease.

PMID- 21945140
TI  - One step immobilization of peptides and proteins by using modified parylene with
      formyl groups.
AB  - One-step immobilization method for peptides and proteins is developed by using
      modified parylene film with formyl groups which is suitable for microplate-based
      immunoassay and SPR biosensor application. The immobilization of peptides and
      proteins is achieved through the covalent bonding of the formyl group with the
      primary amine groups of peptides and proteins, which no additional activation
      step is required. In this work, the immobilization efficiency of parylene-H is
      estimated in comparison with parylene-A and physical adsorption, using
      biotinylated-cyclic citrullinated peptide (biotinylated-CCP), human chorionic
      gonadotropin (hCG) and horseradish peroxidase (HRP) as model proteins. The
      applicability of parylene-H film to SPR biosensor is demonstrated by estimating
      the detection range and sensitivity of SPR biosensor at various thicknesses. The
      immobilization efficiency of parylene-H film for SPR biosensor was compared with
      physical adsorption by using HRP as a model protein.

PMID- 21945141
TI  - Bioelectricity enhancement via overexpression of quorum sensing system in
      Pseudomonas aeruginosa-inoculated microbial fuel cells.
AB  - Low electron transfer efficiency from bacteria to electrodes remains one of the
      major bottlenecks that limit industrial applications of microbial fuel cells
      (MFCs). Elucidating biological mechanism of the electron transfer processes is of
      great help in improving the efficiency of MFCs. Here, we reported that
      Pseudomonas aeruginosa could use different electron shuttles in a MFC under
      different quorum sensing (QS) expression patterns. An electron shuttle (rather
      than phenazines) with a high mid-point potential of 0.20 V (vs. Ag/AgCl-KCl
      saturated electrode) was found to be the dominating shuttle in a wild-type P.
      aeruginosa strain. Strikingly, upon genetic overexpression of rhl QS system in
      this wild-type strain, the electron shuttle was substituted by phenazines
      (pyocyanin and phenazine-1-carboxylate, with a low mid-point potential of -0.17 V
      and -0.28 V, respectively), which directly resulted in an increase of about 1.6
      times of the maximum current of the rhl overexpressed strain over the wild-type
      strain. Our result implied that manipulating electron transfer pathways to
      improve MFCs' efficiency could be achieved by rewiring gene regulatory circuits,
      thus synthetic biology strategies would be adopted.

PMID- 21945142
TI  - Candidate anthelmintic resistance-associated gene expression and sequence
      polymorphisms in a triple-resistant field isolate of Haemonchus contortus.
AB  - An isolate of Haemonchus contortus, UGA/2004, highly resistant to benzimidazoles,
      levamisole, and ivermectin was isolated from sheep at the University of Georgia,
      and passaged through experimentally infected goats. We measured the expression of
      twenty-nine mRNAs encoding drug targets and P-glycoproteins (P-gps), comparing
      the results to a fully susceptible laboratory passaged isolate. Expression levels
      of some nicotinic acetylcholine receptor mRNAs were markedly different in
      UGA/2004. Levels of the Hco-acr-8b mRNA, encoding a truncated subunit, were very
      high in resistant L3, but undetectable in susceptible larvae, with expression of
      the full-length Hco-acr-8a mRNA also significant increased. Expression of Hco-unc
      63 and Hco-unc-29.3 mRNAs was significantly reduced in the resistant larvae.
      Expression of the Hco-glc-3 and Hco-glc-5 mRNAs, encoding glutamate-gated
      chloride channel subunits, were slightly reduced in resistant larvae. We observed
      significant increases in the expression of the Hco-pgp-2 and Hco-pgp-9 mRNAs in
      the UGA/2004 larvae, consistent with previous reports; we also saw a decrease in
      the levels of Hco-pgp-1 mRNA. Treatment of the larvae with ivermectin and
      moxidectin in vitro produced variable and inconsistent changes in P-gp mRNA
      levels. The sequences of the beta-tubulin isotype 1 mRNAs showed that the
      resistant larvae had a resistance-associated allele frequency of >95% at codon
      200 and ~40% and codon 167. No changes at codon 198 were present. The presence of
      the truncated acr-8b mRNA may be a reliable indicator of levamisole resistance,
      but complex changes in gene expression associated with macrocyclic lactone
      resistance make the identification of a single genetic marker for this resistance
      difficult.

PMID- 21945143
TI  - Placental traits and maternal intrinsic factors affected by parity and breed in
      goats.
AB  - The relationship between placental traits and maternal intrinsic factors of
      Saanen, German Fawn and Damascus goats was investigated. Data was collected from
      93 goats. The results of the study demonstrated that there were positive
      correlations between placental weight (PW) and cotyledon number (CN) (r=0.498,
      P<0.01), cotyledon weight (CW) (r=0.880, P<0.01), cotyledon density (CD)
      (r=0.538, P<0.01), cotyledon width (CWI) (r=0.500, P<0.01) cotyledon length (CL)
      (r=0.414, P<0.01) and cotyledon density (CD) (r=0.278, P<0.05). CN was negatively
      correlated with placental efficiency (PE) (r=-0.421, P<0.01) and CD (r=-0.325,
      P<0.05). While expulsion of placenta, right teat length and cotyledon length were
      affected by parity of doe (P<0.05) birth weight (BW), CN, right teat diameter
      (RTD), left teat diameter (LTD), CD, and CL were affected by breed (P<0.01).
      Breed*parity was found significant both for expulsion time of placenta and left
      teat length (LTL) (P<0.05). Damascus goats had a significantly longer duration of
      licking and grooming events than others. Saanen was more likely to require birth
      assistance compared to the German Fawn.

PMID- 21945144
TI  - Context-dependent decisions among options varying in a single dimension.
AB  - Contrary to theories of rational choice, adding alternatives to a choice set can
      change the choices made by both humans and animals. This is usually done by
      adding an inferior decoy to a choice set of two favoured options that are
      characterized on two distinct dimensions. We presented wild, free-living rufous
      hummingbirds (Selasphorus rufus) with choices between two or three options that
      varied in a single dimension only. The options varied in concentration, in volume
      or in corolla length. When the options varied in concentration, the addition of a
      medium option to a choice set of a low and a high concentration caused birds to
      increase their preference for the high option. However, they decreased their
      preference for the high concentration option when a low option was added to a
      choice set of high and medium concentrations. When the options varied only in
      volume, the addition of a high volume option to a choice set of low and medium
      options decreased the birds' preference for the medium option. We saw no effects
      of adding a third option when the options varied in corolla length alone.
      Hummingbirds, then, make context-dependent decisions even when the options vary
      in only a single dimension although which effect occurs seems to depend on the
      dimension being manipulated. None of the current theories alone adequately
      explain these results.

PMID- 21945145
TI  - Performance comparison of peripherally inserted central venous catheters in
      gastrointestinal surgery: a randomized controlled trial.
AB  - BACKGROUND & AIMS: Peripherally inserted central venous catheters (PICC) are long
      term vascular access devices inserted through a peripheral vein of the arm and
      serve as an alternative to traditional central venous catheters. Currently
      different types of PICCs are available. No data, however, are available in regard
      to materials and tip designs. We designed a prospective, randomized trial
      comparing two major PICCs with different material and tip design: a silicone
      catheter with distal side slits (Groshong Catheter) and a polyurethane catheter
      with open-end tip (PI Catheter). METHODS: Twenty-six patients who underwent PICCs
      placement between August 2010 and December 2010 were enrolled in the study. The
      primary endpoint was the completion rate of PICC indication. Secondary endpoints
      were complications rate. RESULT: The completion rate of PICC indication was not
      different significantly (81.8% and 92.9%, p = 0.5648) and the total complication
      rate were also not different significantly (9.1% and 14.3%, P = 1.0000) between
      two catheters. In detail, PI Catheter were associated with a significantly higher
      incidence of catheter occlusion, and Groshong Catheter were associated with a
      significantly hemorrhages after removal. CONCLUSION: There was no difference in
      the durability and the complication between Groshong Catheter and PI Catheter.
      (UMIN Clinical Trial Registry UMIN000005451).

PMID- 21945146
TI  - Cloning and localization of MCdef, a defensin from Manila clams (Ruditapes
      philippinarum).
AB  - A defensin-like peptide was previously detected in hemocytes of Manila clams
      (Ruditapes philippinarum). In the current study, we cloned and characterized this
      defensin, designated MCdef. Cloning produced a full-length gene sequence of 201
      bp predicted to encode a 66-amino-acid precursor protein maturing to a 44-amino
      acid residue. Amino acid sequence analysis showed that MCdef is similar to
      defensins from marine mollusks and ticks. Phylogenetic analysis suggested that
      MCdef is closely related to defensins from Mytilus galloprovincialis
      (Mediterranean mussel) and Crassostrea gigas (Pacific cupped oyster). The three
      dimensional structure of MCdef was modeled using the solution structure of C.
      gigas defensin as a template. With the exception of three variable loop areas,
      the modeled structure of MCdef was identical to that of C. gigas defensin. MCdef
      antiserum was raised against a synthetic MCdef peptide and verified by Western
      blotting using recombinant MCdef. RT-PCR analysis demonstrated high levels of
      MCdef mRNA in hemocytes and adductor, foot, gill, mantle, palp, and siphon
      tissues of Vibrio tapetis-infected Manila clams, whereas in V. tapetis-uninfected
      Manila clams, the level of MCdef mRNA was low in adductor, palp, and siphon
      tissues and even lower in the other tested tissues. Immunohistochemical analysis
      revealed high MCdef expression was detected in the gill, the mantle, and the
      digestive tubules of the diverticulum of V. tapetis-infected Manila clams.
      Minimum inhibitory concentration (MIC) of the purified rMCdef was determined.
      MCdef showed highest activity against Streptococcus iniae and Staphylococcus
      aureus.

PMID- 21945147
TI  - The roles of spatial heterogeneity and adaptive movement in stabilizing (or
      destabilizing) simple metacommunities.
AB  - Adaptive consumer movement and between-patch heterogeneity have both been
      suggested to reduce population fluctuations in spatially subdivided systems.
      These conjectures are explored using models of two-patch consumer-resource
      systems with fitness dependent consumer movement and cyclic dynamics in at least
      one of the patches; neither conjecture applies generally to such systems. Under
      relatively low heterogeneity, highly accurate and rapid adaptive movement most
      often increases both the between-patch correlation of density and the variation
      in the total density of both species compared to a similar system having a low
      rate of random movement. However, such adaptive movement can decrease between
      patch correlation and global population variability when (1) the consumer's
      movement is moderately sensitive to fitness differences and heterogeneity is
      relatively low, or (2) one of the patches would be stable in isolation, and the
      stable patch supports a sufficiently large consumer population. In both cases,
      the dynamics are typically either a stable equilibrium or a simple anti-phase
      cycle with low variation in total population size. Under adaptive movement,
      population variability is often lowest for intermediate levels of heterogeneity,
      but monotonic increases or decreases with increasing spatial heterogeneity are
      possible, depending on the fitness sensitivity of movement and how the
      characteristic that differs between patches affects within-patch stability and
      population size. High rates of random movement can lead to greater stability than
      adaptive movement when consumers are very efficient.

PMID- 21945148
TI  - Seasonal spread and control of Bluetongue in cattle.
AB  - Bluetongue is a seasonal midge-borne disease of ruminants with economic
      consequences on herd productivity and animal trade. Recently, two new modes of
      transmission have been demonstrated in cattle for Bluetongue virus serotype 8
      (BTV8): vertical and pseudo-vertical transmission. Our objective was to model the
      seasonal spread of BTV8 over several years in a homogeneous population of cattle,
      and to evaluate the effectiveness of vaccination strategies. We built a
      deterministic mathematical model accounting for the seasonality in vector
      abundance and all the modes of transmission. We proposed a counterpart of the
      basic reproduction number (R(0)) in a seasonal context (R(S)). Set A(t) is the
      number of secondary cases produced by a primary case introduced at time t. R(S)
      is the average of A(t). It is a function of midge abundance and vaccination
      strategy. We also used A*, the maximum of A(t), as an indicator of the risk of an
      epidemic. Without vaccination, the model predicted a large first epidemic peak
      followed by smaller annual peaks if R(S)>1. When R(S)<1, small epidemics could
      occur if A* >1. Vaccination reduced R(S) and A* to less than one, but almost
      perfect vaccine efficacy and coverage were required to ensure no epidemics
      occurred. However, a lower coverage resulting in R(S)>1 could decrease infection
      prevalence. A further step would be to optimize vaccination strategies by
      targeting an appropriate period of the year to implement the vaccination.

PMID- 21945149
TI  - Electrodiffusion model simulation of the potassium channel.
AB  - The drift-diffusion (Poisson-Nernst-Planck) model is applied to the potassium
      channel in a biological membrane plus surrounding solution baths. Two-dimensional
      cylindrically symmetric simulations of the K channel in KCl solutions are
      presented which show significant boundary layers at the ends of the channel and
      display the spreading of charge into the bath regions. The computed current
      voltage curve shows excellent agreement with experimental measurements. In
      addition, the response of the K channel to time-dependent applied voltages is
      investigated.

PMID- 21945150
TI  - Involvement of orexin in the regulation of stress, depression and reward in
      alcohol dependence.
AB  - There is growing evidence from preclinical studies for an involvement of orexins
      (ORX) in the regulation of stress, affectivity and addictive behavior. The aim of
      our study was to gather corresponding clinical data and to elucidate the
      relationships between alcohol withdrawal stress, ORX plasma concentration and
      psychopathology. A consecutive sample of thirty-four alcohol-dependent inpatients
      was included in the study. Blood was drawn at onset of withdrawal and following 2
      weeks of controlled abstinence in order to assess ORX, ACTH and cortisol plasma
      concentrations. In parallel, we assessed clinically relevant psychological
      distress symptoms applying the Brief Symptom Inventory (BSI). We found a
      significant positive correlation between ORX and global distress indices of the
      BSI (p <= 0.05). In a regression model, ORX concentration during acute withdrawal
      explained 24% of the variance of symptom severity (p<0.01). No association with
      craving, ACTH or cortisol plasma concentration was detected. Our results suggest
      an involvement of ORX in the affective dysregulation seen commonly in alcohol
      dependent patients during alcohol withdrawal. Moreover, the effects on global
      distress indices as well as the earlier studied effects on reinstatement of drug
      seeking behaviors may point on an involvement of ORX in impaired brain stress
      systems.

PMID- 21945151
TI  - Exclusion of CTSB and FDFT1 as positional and functional candidate genes for
      keratolytic winter erythema (KWE).
AB  - BACKGROUND: Keratolytic winter erythema (KWE) or Oudtshoorn skin disease is a
      rare autosomal dominant monogenic disorder of epidermal keratinisation
      characterized clinically by cyclical peeling of the palms and soles. Due to a
      founder effect many KWE families have been identified in South Africa and the
      gene has been localized to 8p23.1-22, but the causal gene has yet to be
      identified. OBJECTIVE: To examine two compelling positional and functional
      candidate genes within the critical region on 8p: cathepsin B (CTSB), a lysosomal
      cysteine protease localized to pericellular spaces between keratinocytes,
      possibly playing a role in cell-cell adhesion; and farnesyl-diphosphate
      farnesyltransferase (FDFT1), a membrane-associated enzyme in cholesterol
      biosynthesis which, among its many functions, plays a role in barrier
      permeability and integrity. METHOD: Mutation screening of the coding regions,
      5'UTRs and intron/exon boundaries of CTSB and FDFT1 in genomic DNA and cDNA of
      patients affected with KWE. Relative gene expression profiles of CTSB and FDFT1
      in palmoplantar skin biopsies were assessed by real-time RT-PCR. RESULTS: No DNA
      variants that segregate exclusively with KWE were identified. There was no
      significant difference in the CTSB expression profiles but a trend towards
      increased expression of FDFT1 was observed in the skin of affected individuals
      (p=0.063). This observation prompted analysis of the FDFT1 promoter region;
      however, no genetic variants segregating with the KWE phenotype were observed and
      it is likely that the increased expression was triggered in response to skin
      inflammation and peeling. CONCLUSION: CTSB and FDFT1 are excluded as candidates
      for KWE.

PMID- 21945152
TI  - Effects of theta burst stimulation on motor cortex excitability in Parkinson's
      disease.
AB  - OBJECTIVE: Long-term potentiation (LTP)-like plasticity induced by paired
      associative stimulation (PAS) is impaired in Parkinson's disease (PD).
      Intermittent theta burst stimulation (iTBS) is another rTMS protocol that
      produces LTP-like effects and increases cortical excitability but its effects are
      independent of afferent input. The aim of the present study was to examine the
      effects of iTBS on cortical excitability in PD. METHODS: iTBS was applied to the
      motor cortex in 10 healthy subjects and 12 PD patients ON and OFF dopaminergic
      medications. Motor evoked potential (MEP) before and for 60 min after iTBS were
      used to examine the changes in cortical excitability induced by iTBS. Paired
      pulse TMS was used to test whether intracortical circuits, including short
      interval intracortical inhibition, intracortical facilitation, short and long
      latency afferent inhibition, were modulated by iTBS. RESULTS: After iTBS, the
      control, PD ON and OFF groups had similar increases in MEP amplitude compared to
      baseline over the course of 60 min. Changes in intracortical circuits induced by
      iTBS were also similar for the different groups. CONCLUSIONS: iTBS produced
      similar effects on cortical excitability for PD patients and controls.
      SIGNIFICANCE: Spike-timing dependent heterosynaptic LTP-like plasticity induced
      by PAS may be more impaired in PD than frequency dependent homosynaptic LTP-like
      plasticity induced by iTBS.

PMID- 21945153
TI  - Corticospinal excitability in patients with secondary dystonia due to focal
      lesions of the basal ganglia and thalamus.
AB  - OBJECTIVE: To investigate the possible correlations between clinico-radiological
      features and pathophysiological mechanisms in patients with dystonia secondary to
      focal brain lesions. METHODS: Single and paired-pulse transcranial magnetic
      stimulation was used to assess corticospinal excitability in 10 patients (4
      females; mean age 61) and a group of normal controls. Active threshold, latency
      and amplitude of motor evoked potentials (MEPs), silent period (SP) duration and
      short-interval intracortical inhibition (SICI) were evaluated. RESULTS: Patients
      with lesions involving the putamen and caudate presented with dystonic postures
      at rest. TMS assessment in these subjects showed increased MEP amplitude on the
      affected side and a bilateral decrease of SP duration and SICI. When the lesion
      spared the putamen and caudate, mainly involving the thalamus, the clinical
      picture was dominated by slow repetitive involuntary movements and tremor. In the
      affected side of these subjects the MEP amplitude was reduced and the MEP
      threshold was increased. CONCLUSIONS: When putamen and caudate were lesioned, the
      patients presented with dystonic postures at rest; furthermore the patients
      showed changes of corticospinal excitability in comparison to both healthy
      subjects and other dystonic patients. SIGNIFICANCE: There are correlations
      between type of dystonia, site of the lesion and neurophysiological findings.

PMID- 21945154
TI  - Inhibition of Abeta(25-35)-induced cell apoptosis by low-power-laser-irradiation
      (LPLI) through promoting Akt-dependent YAP cytoplasmic translocation.
AB  - Deposition of amyloid-beta-peptide (Abeta) in the brain is considered a
      pathological hallmark of Alzheimer's disease (AD). Our previous studies show that
      Yes-associated protein (YAP) is involved in the regulation of apoptosis induced
      by Abeta(25-35) through YAP nuclear translocation and its pro-apoptotic function
      is mediated by its interaction with p73. In the present study, we first found
      that Low-power laser irradiation (LPLI) promoted YAP cytoplasmic translocation
      and inhibited Abeta(25-35)-induced YAP nuclear translocation. Moreover, the
      cytoplasmic translocation was in an Akt-dependent manner. Activated Akt by LPLI
      phosphorylated YAP on ser127 (S127) and resulted in decreasing the interaction
      between YAP and p73, and in suppressing the proapoptotic gene bax expression
      following Abeta(25-35) treatment. Inhibition of Akt expression by siRNA
      significantly abolished the effect of LPLI. More importantly, LPLI could inhibit
      Abeta(25-35)-induced cell apoptosis through activation of Akt/YAP/p73 signaling
      pathway. Therefore, our findings first suggest that YAP may be a therapeutic
      target and these results directly point to a potential therapeutic strategy for
      the treatment of AD through Akt/YAP/p73 signaling pathway with LPLI.

PMID- 21945155
TI  - Thermo-sensitive transient receptor potential vanilloid channel-1 regulates
      intracellular calcium and triggers chromogranin A secretion in pancreatic
      neuroendocrine BON-1 tumor cells.
AB  - Transient receptor potential channels (TRPs) regulate tumor growth via calcium
      dependent mechanisms. The (thermosensitive) capsaicin receptor TRPV1 is
      overexpressed in numerous highly aggressive cancers. TRPV1 has potent
      antiproliferative activity and is therefore potentially applicable in targeted
      therapy of malignancies. Recently, we characterized TRPM8 functions in pancreatic
      neuroendocrine tumors (NETs), however, the role of TRPV1 is unknown. Here, we
      studied the expression and the role of TRPV1 in regulating intracellular Ca(2+)
      and chromogranin A (CgA) secretion in pancreatic NET BON-1 cell line and in
      primary NET cells (prNET). TRPV1 expression was detected by RT-PCR, Western blot
      and immunofluorescence. Intracellular free Ca(2+) ([Ca(2+)](i)) was measured by
      fura-2; TRPV1 channel currents by the planar patch-clamp technique. Nonselective
      cation currents were analyzed by a color-coded plot method and CgA secretion by
      ELISA. Pancreatic BON-1 cells and NETs express TRPV1. Pharmacological blockade of
      TRPs by La(3+) (100 MUM) or by ruthenium-red (RuR) or by capsazepine (CPZ) (both
      at 10 MUM) suppressed the capsaicin (CAP)- or heat-stimulated increase of
      [Ca(2+)](i) in NET cells. CAP (20 MUM) also increased nonselective cation channel
      currents in BON-1 cells. Furthermore, CAP (10 MUM) stimulated CgA secretion,
      which was inhibited by CPZ or by RuR (both 10 MUM). La(3+) potently reduced both
      stimulated and the basal CgA secretion. Our study shows for the first time that
      TRPV1 is expressed in pancreatic NETs. Activation of TRPV1 translates into
      changes of intracellular Ca(2+), a known mechanism triggering the secretion of
      CgA. The clinical relevance of TRPV1 activation in NETs requires further
      investigations.

PMID- 21945157
TI  - ABO research in the modern era of genomics.
AB  - Research on ABO has advanced significantly in recent years. A database was
      established to manage the sequence information of an increasing number of novel
      alleles. Genome sequencings have identified ABO orthologues and paralogues in
      various organisms and enhanced the knowledge on the evolution of the ABO and
      related genes. The most prominent advancements include clarification of the
      association between ABO and different disease processes. For instance, ABO status
      affects the infectivity of certain strains of Helicobacter pylori and Noroviruses
      as well as the sequestration and rosetting of red blood cells infected with
      Plasmodium falciparum. Genome-wide association studies have conclusively linked
      the ABO locus to pancreatic cancer, venous thromboembolism, and myocardial
      infarction in the presence of coronary atherosclerosis. These findings suggest
      ABO's important role in determining an individual's susceptibility to such
      diseases. Furthermore, our understanding of the structures of A and B
      transferases and their enzymology has been dramatically improved. ABO has also
      become a research subject in neurobiology and the preparation of
      artificial/universal blood and became a topic in the pseudoscience of "blood type
      diets." With such new progress, it has become evident that ABO is a critical
      player in the modern era of genomic medicine. This article provides the most up
      to-date information regarding ABO genomics.

PMID- 21945156
TI  - Endocardial cell epithelial-mesenchymal transformation requires Type III TGFbeta
      receptor interaction with GIPC.
AB  - An early event in heart valve formation is the epithelial-mesenchymal
      transformation (EMT) of a subpopulation of endothelial cells in specific regions
      of the heart tube, the endocardial cushions. The Type III TGFbeta receptor
      (TGFbetaR3) is required for TGFbeta2- or BMP-2-stimulated EMT in atrioventricular
      endocardial cushion (AVC) explants in vitro but the mediators downstream of
      TGFbetaR3 are not well described. Using AVC and ventricular explants as an in
      vitro assay, we found an absolute requirement for specific TGFbetaR3 cytoplasmic
      residues, GAIP-interacting protein, C terminus (GIPC), and specific Activin
      Receptor-Like Kinases (ALK)s for TGFbetaR3-mediated EMT when stimulated by
      TGFbeta2 or BMP-2. The introduction of TGFbetaR3 into nontransforming ventricular
      endocardial cells, followed by the addition of either TGFbeta2 or BMP-2, results
      in EMT. TGFbetaR3 lacking the entire cytoplasmic domain, or only the 3C-terminal
      amino acids that are required to bind GIPC, fails to support EMT in response to
      TGFbeta2 or BMP-2. Overexpression of GIPC in AVC endocardial cells enhanced EMT
      while siRNA-mediated silencing of GIPC in ventricular cells overexpressing
      TGFbetaR3 significantly inhibited EMT. Targeting of specific ALKs by siRNA
      revealed that TGFbetaR3-mediated EMT requires ALK2 and ALK3, in addition to ALK5,
      but not ALK4 or ALK6. Taken together, these data identify GIPC, ALK2, ALK3, and
      ALK5 as signaling components required for TGFbetaR3-mediated endothelial cell
      EMT.

PMID- 21945158
TI  - One pathway to academic success: autobiography of Dr Ronald G. Strauss.
AB  - Often, I have been asked by "junior faculty"-who are usually burdened by
      substantial responsibilities in service and teaching-how they can launch their
      career in research as a means to succeed in academic medicine. Obviously, the
      answers/solutions are as diverse as are the circumstances of each questioner. In
      the following article, I offer the approach that I applied to my career
      acknowledging that "one shoe doesn't fit all" and that others will advise
      differently. However, one truism exists whenever one seeks excellence in anything
      the opportunity must be present to commit uninterrupted time for
      thought/concentration, organization, training/mentoring/study, and effort/hard
      work. Without such an opportunity, success in research will be elusive.

PMID- 21945159
TI  - Angiographic and histologic comparison of injectable, expansile hydrogel embolic
      and pushable AZUR embolic devices in porcine arteries.
AB  - PURPOSE: To compare an injectable hydrogel embolic device with a pushable AZUR
      device procedurally, angiographically, and histologically in the embolization of
      porcine arteries. MATERIALS AND METHODS: In 12 pigs, embolization of renal,
      gluteal, and hepatic or thoracic arteries was performed with either injectable
      hydrogel embolic devices (two arteries per pig) or an AZUR device (one artery per
      pig). Follow-up angiography was performed before sacrifice in five pigs at 7 days
      after embolization and seven pigs at 90 days after embolization. The harvested
      tissues were evaluated histologically. Continuous and ordinal results were
      compared using analysis of variance and chi(2) tests. RESULTS: For the sites with
      embolization performed with injectable hydrogel, complete angiographic occlusion
      was obtained in 21 of 24 (88%) sites after treatment, 10 of 10 (100%) sites at 7
      days, and 10 of 14 (72%) sites at 90 days. For the sites with embolization
      performed with AZUR devices, complete angiographic occlusion was obtained in 10
      of 12 (83%) sites after treatment, 4 of 5 (80%) sites at 7 days, and 5 of 7 (72%)
      sites at 90 days. Statistically significant differences in angiographic occlusion
      were not observed at 7 days (P = .13) or 90 days (P = .35). The embolization time
      of the injectable hydrogel group (14 minutes +/- 8) was significantly reduced (P
      = .02) compared with the AZUR group (22 minutes +/- 12). Differences between the
      groups in arterial wall damage were not evident at either 7 days or 90 days,
      although greater damage was observed in both groups at 90 days. In both groups,
      inflammation was nonexistent to minimal at 7 days and minimal to mild at 90 days.
      CONCLUSIONS: Embolization of porcine arteries was as effective with injectable
      hydrogel embolic devices as pushable AZUR devices, as evidenced by the
      procedural, angiographic, and histologic results.

PMID- 21945160
TI  - Isolation of a gastroprotective arabinoxylan from sugarcane bagasse.
AB  - After industrial processing, one-third of sugarcane culms is converted into
      residual bagasse. The xylan-rich hemicellulose components of the bagasse were
      extracted with hot aqueous alkali (AX-CRUDE). Approximately 82% of the extracted
      hemicelluloses was precipitated with ethanol (AX-PET). Both AX-CRUDE and AX-PET
      contained an arabinoxylan as confirmed by 13C NMR and methylation analysis.
      Fraction AX-PET was fed to female Wistar rats with ethanol-induced gastric
      lesions. Oral administrations of 30, 100, and 300 mg/kg reduced the gastric
      lesion area by over 50%, and replenished ethanol-induced depletion of
      glutathione. The polysaccharide also increased mucus production by over 70%,
      indicating its cytoprotective action on experimentally induced gastric ulcers.
      These findings are significant, since a biologically active compound can be
      extracted in high yields from an abundant, readily available residue.

PMID- 21945161
TI  - Potential energy production from algae on marginal land in China.
AB  - This study is aimed to systematically estimate marginal land resources with
      different grades (total area; land with certain eco-environmental-economic
      feasibility; centralized reserve land) in China, and evaluate potential energy
      production from microalgae on marginal lands in the long-, mid- and near-term,
      based on a model. The annual potential energy production from algae in total
      marginal land of China (APEMC) was estimated to 4.19 billion standard coal
      equivalent (tce), far more than total annual energy consumption equivalent in
      China (TECCE) in 2007. For microalgae with 35% lipid content, the APEMC in the
      mid-term would be 37.6-65.8% of the TECCE in 2007. The corresponding annual CO(2)
      emission mitigation by replacement of fossil fuels by algal bioenergy would be
      4.27-7.44 billiont. Although Southwest China provides the highest potential algae
      production in the long-term, Northwest China provides the highest value in the
      near-term.

PMID- 21945162
TI  - Analysis of petroleum biodesulfurization in an airlift bioreactor using response
      surface methodology.
AB  - For the first time, growing cells of Gordonia alkanivorans RIPI90A were used for
      biodesulfurization (BDS) of diesel. This process was carried out in an internal
      airlift bioreactor. BDS parameters (oil/water phase ratio and initial sulfur
      concentration) were optimized in flasks using response surface methodology.
      Predicted results were found to be in good agreement with experimental results.
      Initial sulfur concentration had a remarkable effect on BDS process. Maximum
      removal of sulfur (21 mg/l) can be achieved at oil/water phase ratio of 25% (v/v)
      and initial sulfur concentration of 28 mg/l. Moreover, effect of superficial gas
      velocity (Ug) and working volume (v) on volumetric gas liquid mass transfer
      coefficient was studied in an airlift bioreactor for BDS of diesel. The best
      results were achieved at Ug and v of 2.5l/min and 6.6l, respectively.
      Subsequently, BDS of diesel was investigated in an airlift bioreactor under
      optimized conditions. Sulfur reduction after 30 h was 14 mg/l.

PMID- 21945163
TI  - Efficient and simple method for determination of suspendibility of bio-inoculant
      suspensions.
AB  - This study assessed the utilization of viscosity and zeta potential as a novel
      method to evaluate suspendibility of formulation of Sinorhizobium meliloti grown
      in starch industry wastewater for use as bio-inoculants. For this objective,
      sorbitol was used as a suspending agent at concentrations of 0 to 10% w/v. Model,
      based on multiple linear regression (with pH as dependant variable, and zeta
      potential, average particle size and sorbitol concentration as independent
      variables) demonstrated an important relation which was significant (p<0.001,
      R2=0.98). Sigmoid regression revealed a significant relation between zeta
      potential and suspendibility with p value=0.007 and R-squared=0.86, and between
      viscosity and suspendibility (p value<0.0001 and R squared=0.9823). Thus, these
      direct correlations established the lowering of measurement time from 12 h to 5
      min.

PMID- 21945164
TI  - Optimization of CO2 laser-based pretreatment of corn stover using response
      surface methodology.
AB  - CO2 laser pretreatment to improve the enzymatic hydrolysis of corn stover for
      production of monosaccharide, was investigated. Response surface methodology
      (RSM), at a three-variable, three-level experiment Box-Behnken design (BBD)
      established the following optimum pretreatment parameters: time, 67.53 min;
      power, 264.33 W; and liquid-to-solid ratio, 21.29:1 (mL/g). Under these
      conditions, the reducing sugars produced was 4.941 mg/mL for cellulase
      hydrolysis. This amount matched the predicted value and increased cellulase
      hydrolysis from 14.47% to 30.84%. Scanning electron microscopy (SEM) showed that
      CO2 laser pretreatment converted the smooth into a rough and porous surface,
      which promoted the enzyme access and resulted in a high specific reducing sugars
      production rate.

PMID- 21945165
TI  - Effect of fiber diameter on the behavior of biofilm and anodic performance of
      fiber electrodes in microbial fuel cells.
AB  - A series of fiber electrodes with fiber diameters ranging from about 10 to 0.1
      MUm were tested as anodes in microbial fuel cells to study the effect of fiber
      diameter on the behavior of biofilm and anodic performance of fiber electrodes. A
      simple method of biofilm fixation and dehydration was developed for biofilm
      morphology characterization. Results showed that the current density of fiber
      anodes increased until the fiber diameter approached 1 MUm which was about the
      length of the dominant microorganisms in biofilm. The highest current density was
      3.08 mA cm(-2), which was obtained from fiber anode with high porosity of over
      99% and fiber diameter of 0.87 MUm. It was believed that the high current density
      was attributed to the high porosity, as well as proper fiber diameter which
      ensured formation of thick and continuous solid biofilms.

PMID- 21945166
TI  - Hydroprocessing of sunflower oil-gas oil blends over sulfided Ni-Mo-Al-zeolite
      beta composites.
AB  - Mixtures of sunflower oil and a straight run gas oil in the diesel fuel range
      were hydroprocessed over sulfided NiO(3%)-MoO3(12%)-gamma-Al2O3 incorporating 0,
      15 or 30 wt.% zeolite beta (BEA). The studies were carried out at 320-350 
      degrees C; 30-60 bars, and weight hourly space velocities (WHSV), 1-4 h(-1).
      Catalyst containing 30% BEA achieved nearly 100 % conversion of the vegetable oil
      into hydrocarbons at 330  degrees C, 60 bars and a WHSV of 2 h(-1) compared to
      95.5% by the Ni-Mo-gamma-alumina catalyst without BEA. Hydroprocessing with
      blends containing oleic acid revealed that the catalysts were able to transform
      the acid into hydrocarbons. An analysis of the ratios of the n-C18 and n-C17
      paraffins formed from the vegetable oil at different process conditions revealed
      that the catalyst containing 15% BEA was most active for hydrodeoxygenation. The
      gas oil-hydrodesulfurization activity of the Ni-Mo-Al2O3 was enhanced by the
      addition of BEA by more than 10%.

PMID- 21945167
TI  - Dosimetric evaluation of a three-phase adaptive radiotherapy for nasopharyngeal
      carcinoma using helical tomotherapy.
AB  - Adaptive radiotherapy (ART) has been introduced to correct the radiation-induced
      anatomic changes in head and neck cases during a treatment course. This study
      evaluated the potential dosimetric benefits of applying a 3-phase adaptive
      radiotherapy protocol in nasopharyngeal carcinoma (NPC) patients compared with
      the nonadaptive single-phase treatment protocol. Ten NPC patients previously
      treated with this 3-phase radiation protocol using Hi-Art Tomotherapy were
      recruited. Two new plans, PII-ART and PIII-ART, were generated based on the up-to
      date computed tomography (CT) images and contours and were used for treatment in
      phase two (PII; after 25th fraction) and phase three (PIII; after 35th fraction),
      respectively. To simulate the situation of no replanning, 2 hybrid plans denoted
      as PII-NART and PIII-NART were generated using the original contours pasted on
      the PII- and PIII-CT sets by CT-CT fusion. Dosimetric comparisons were made
      between the NART plans and the corresponding ART plans. In both PII- and PIII
      NART plans, the doses to 95% of all the target volumes (D95) were increased with
      better dose uniformity, whereas the organs at risk (OARs) received higher doses
      compared with the corresponding ART plans. Without replanning, the total dose to
      1% of brainstem and spinal cord (D1) significantly increased 7.87 +/- 7.26% and
      10.69 +/- 6.72%, respectively (P = 0.011 and 0.001, respectively), in which 3
      patients would have these structures overdosed when compared with those with two
      replannings. The total maximum doses to the optic chiasm and pituitary gland and
      the mean doses to the left and right parotid glands were increased by 10.50 +/-
      10.51%, 8.59 +/- 6.10%, 3.03 +/- 4.48%, and 2.24 +/- 3.11%, respectively (P =
      0.014, 0.003, 0.053, and 0.046, respectively). The 3-phase radiotherapy protocol
      showed improved dosimetric results to the critical structures while keeping
      satisfactory target dose coverage, which demonstrated the advantages of ART in
      helical tomotherapy of NPC.

PMID- 21945168
TI  - Addition of a third field significantly increases dose to the brachial plexus for
      patients undergoing tangential whole-breast therapy after lumpectomy.
AB  - Our goal was to evaluate brachial plexus (BP) dose with and without the use of
      supraclavicular (SCL) irradiation in patients undergoing breast-conserving
      therapy with whole-breast radiation therapy (RT) after lumpectomy. Using the
      standardized Radiation Therapy Oncology Group (RTOG)-endorsed guidelines
      delineation, we contoured the BP for 10 postlumpectomy breast cancer patients.
      The radiation dose to the whole breast was 50.4 Gy using tangential fields in 1.8
      Gy fractions, followed by a conedown to the operative bed using electrons (10
      Gy). The prescription dose to the SCL field was 50.4 Gy, delivered to 3-cm depth.
      The mean BP volume was 14.5 +/- 1.5 cm(3). With tangential fields alone, the
      median mean dose to the BP was 0.57 Gy, the median maximum dose was 1.93 Gy, and
      the irradiated volume of the BP receiving 40, 45, and 50 Gy was 0%. When the
      third (SCL field) was added, the dose to the BP was significantly increased (P =
      .01): the median mean dose to the BP was 40.60 Gy, and the median maximum dose
      was 52.22 Gy. With 3-field RT, the median irradiated volume of the BP receiving
      40, 45, and 50 Gy was 83.5%, 68.5%, and 24.6%, respectively. The addition of the
      SCL field significantly increases dose to the BP. The possibility of increasing
      the risk of BP morbidity should be considered in the context of clinical decision
      making.

PMID- 21945169
TI  - Simplified field-in-field technique for a large-scale implementation in breast
      radiation treatment.
AB  - We wanted to evaluate a simplified "field-in-field" technique (SFF) that was
      implemented in our department of Radiation Oncology for breast treatment. This
      study evaluated 15 consecutive patients treated with a simplified field in field
      technique after breast-conserving surgery for early-stage breast cancer.
      Radiotherapy consisted of whole-breast irradiation to the total dose of 50 Gy in
      25 fractions, and a boost of 16 Gy in 8 fractions to the tumor bed. We compared
      dosimetric outcomes of SFF to state-of-the-art electronic surface compensation
      (ESC) with dynamic leaves. An analysis of early skin toxicity of a population of
      15 patients was performed. The median volume receiving at least 95% of the
      prescribed dose was 763 mL (range, 347-1472) for SFF vs. 779 mL (range, 349-1494)
      for ESC. The median residual 107% isodose was 0.1 mL (range, 0-63) for SFF and
      1.9 mL (range, 0-57) for ESC. Monitor units were on average 25% higher in ESC
      plans compared with SFF. No patient treated with SFF had acute side effects
      superior to grade 1-NCI scale. SFF created homogenous 3D dose distributions
      equivalent to electronic surface compensation with dynamic leaves. It allowed the
      integration of a forward planned concomitant tumor bed boost as an additional
      multileaf collimator subfield of the tangential fields. Compared with electronic
      surface compensation with dynamic leaves, shorter treatment times allowed better
      radiation protection to the patient. Low-grade acute toxicity evaluated weekly
      during treatment and 2 months after treatment completion justified the pursuit of
      this technique for all breast patients in our department.

PMID- 21945170
TI  - Bowel sparing in pediatric cranio-spinal radiotherapy: a comparison of combined
      electron and photon and helical TomoTherapy techniques to a standard photon
      method.
AB  - The aim of this study was to compare the dose to organs at risk (OARs) from
      different craniospinal radiotherapy treatment approaches available at the
      Northern Centre for Cancer Care (NCCC), with a particular emphasis on sparing the
      bowel. METHOD: Treatment plans were produced for a pediatric medulloblastoma
      patient with inflammatory bowel disease using 3D conformal 6-MV photons (3DCP),
      combined 3D 6-MV photons and 18-MeV electrons (3DPE), and helical photon
      TomoTherapy (HT). The 3DPE plan was a modification of the standard 3DCP
      technique, using electrons to treat the spine inferior to the level of the
      diaphragm. The plans were compared in terms of the dose-volume data to OARs and
      the nontumor integral dose. RESULTS: The 3DPE plan was found to give the lowest
      dose to the bowel and the lowest nontumor integral dose of the 3 techniques.
      However, the coverage of the spine planning target volume (PTV) was least
      homogeneous using this technique, with only 74.6% of the PTV covered by 95% of
      the prescribed dose. HT was able to achieve the best coverage of the PTVs (99.0%
      of the whole-brain PTV and 93.1% of the spine PTV received 95% of the prescribed
      dose), but delivered a significantly higher integral dose. HT was able to spare
      the heart, thyroid, and eyes better than the linac-based techniques, but other
      OARs received a higher dose. CONCLUSIONS: Use of electrons was the best method
      for reducing the dose to the bowel and the integral dose, at the expense of
      compromised spine PTV coverage. For some patients, HT may be a viable method of
      improving dose homogeneity and reducing selected OAR doses.

PMID- 21945171
TI  - Molecular genetic testing of uveal melanoma from routinely processed and stained
      cytology specimens.
AB  - In the following study we investigated the utility of molecular genetic testing
      of the DNA extracted from routinely stained and processed smears from uveal
      melanoma (UM). Smears from five uveal melanoma cell lines and 12 primary tumors
      were prepared and stained with Papanicolaou and Romanowsky stains. Genotyping was
      carried out utilizing 14 microsatellite markers on chromosomes 3, 6 and 8.
      Mutational screening for alterations in GNAQ and GNA11 genes was carried out by
      restriction fragment length polymorphism. The results were compared to those
      obtained through direct sequencing of frozen tumor tissues. High quality DNA was
      extracted from the stained slides with no difference in the efficiency of DNA
      extraction between the two staining techniques. The extracted DNA was of adequate
      quality for genotyping and mutational screening. DNA extracted from approximately
      200 tumor cells is sufficient for reproducible testing of allelic imbalances and
      for studying the common somatic mutations in GNAQ and GNA11 genes. In conclusion,
      we presented the feasibility of utilizing routinely stained cytology smears from
      UM for molecular genetic testing. The DNA obtained is of sufficient quality to
      carry out genotyping for markers on chromosome 3, 6 and 8, as well as screening
      for somatic mutations in GNAQ and GNA11 genes.

PMID- 21945173
TI  - Alternating hemiplegia of childhood: metabolic studies in the largest European
      series of patients.
AB  - Alternating hemiplegia of childhood (AHC) is a rare disorder with diagnosis based
      on clinical criteria, as no laboratory, neuroradiological or genetic markers are
      currently available. The pathogenic mechanisms are still an enigma. Some
      hypotheses have been proposed such as hemiplegic migraine variant, epileptic
      mechanism, channelopathy and mitochondrial disorder, but none of these has been
      confirmed. Our aim was to analyze the results of metabolic studies performed on a
      series of 157 European patients who fulfilled diagnostic criteria for AHC. We
      tried to find a common metabolic abnormality, related with AHC. We did not find
      significant abnormalities in basic metabolic screening, at different ages.
      Neurotransmitters in cerebrospinal fluid (n = 26) were normal in all of the
      patients. Mitochondrial respiratory chain enzyme activities were analyzed in 19
      muscle biopsies; in 4 cases, different MRC enzyme deficiencies were demonstrated,
      ranging from mild-unspecific deficiencies to more profound and probably primary
      defects. Although we did not find specific metabolic markers in our series, some
      metabolic disorders such as pyruvate dehydrogenase deficiency, MELAS, cerebral
      glucose transporter defect and neurotransmitter deficiency can exhibit symptoms
      similar to those of AHC and need to be ruled out before a diagnosis of AHC can be
      established. Further studies including high-throughput diagnostic technologies
      seem necessary to elucidate the etiology of this severe and enigmatic disorder.

PMID- 21945172
TI  - FGF signaling regulates rod photoreceptor cell maintenance and regeneration in
      zebrafish.
AB  - Fgf signaling is required for many biological processes involving the regulation
      of cell proliferation and maintenance, including embryonic patterning, tissue
      homeostasis, wound healing, and cancer progression. Although the function of Fgf
      signaling is suggested in several different regeneration models, including
      appendage regeneration in amphibians and fin and heart regeneration in zebrafish,
      it has not yet been studied during zebrafish photoreceptor cell regeneration.
      Here we demonstrate that intravitreal injections of FGF-2 induced rod precursor
      cell proliferation and photoreceptor cell neuroprotection during intense light
      damage. Using the dominant-negative Tg(hsp70:dn-fgfr1) transgenic line, we found
      that Fgf signaling was required for homeostasis of rod, but not cone,
      photoreceptors. Even though fgfr1 is expressed in both rod and cone
      photoreceptors, we found that Fgf signaling differentially affected the
      regeneration of cone and rod photoreceptors in the light-damaged retina, with the
      dominant-negative hsp70:dn-fgfr1 transgene significantly repressing rod
      photoreceptor regeneration without affecting cone photoreceptors. These data
      suggest that rod photoreceptor homeostasis and regeneration is Fgf-dependent and
      that rod and cone photoreceptors in adult zebrafish are regulated by different
      signaling pathways.

PMID- 21945174
TI  - Impact of maternal probiotic-supplemented dietary counseling during pregnancy on
      colostrum adiponectin concentration: a prospective, randomized, placebo
      controlled study.
AB  - BACKGROUND: The breast milk bioactive substances such as adiponectin, have a
      presumably long-term impact upon the health and well-being of a child. AIM: To
      determine the impact of probiotic-supplemented dietary counseling during
      pregnancy on colostrum adiponectin concentration. STUDY DESIGN AND SUBJECTS:
      Altogether 256 pregnant women were randomized into three study groups: dietary
      intervention with probiotics (diet/probiotics) or with placebo (diet/placebo) and
      a control group (control/placebo). The intervention group received dietary
      counseling provided by a nutritionist, the main focus being the amount and the
      type of dietary fat. The probiotics used were Lactobacillus rhamnosus GG and
      Bifidobacterium lactis in combination. Dietary intake was evaluated by food
      records at every trimester of pregnancy. Breast milk samples were collected after
      birth (colostrum) for adiponectin concentration analysis (n=181). RESULTS: The
      dietary intervention increased the colostrum adiponectin concentration (ng/mL,
      geometric mean [95% CI]), the difference being significant when comparing to the
      control group; 12.7 [10.6-29.7] vs. 10.2 [9.9-13.2], P=0.024. Maternal weight
      gain during pregnancy (kg) correlated inversely with colostrum adiponectin
      concentration; beta (SE)=-1.7 (0.1), P=0.020, and gestational diabetes mellitus
      was associated with the likelihood of adiponectin concentration falling into the
      lowest quartile; OR 2.36, 95% CI 1.1-3.2, P=0.028. CONCLUSIONS: In showing that
      the colostrum adiponectin concentration is markedly dependent on maternal diet
      and nutritional status during pregnancy, and considering that colostrum
      adiponectin has potential effects on metabolism, nutrition, and immune function
      in the neonates, the results of this study underscore the importance of the
      metabolic homeostasis of the mother for the child's initial nutritional
      environment.

PMID- 21945175
TI  - CCR4 dependent migration of Foxp3+ Treg cells to skin grafts and draining lymph
      nodes is implicated in enhanced graft survival in CD200tg recipients.
AB  - We have previously reported that transgenic overexpression of CD200 in either
      mouse skin graft donors or recipients significantly enhances skin allograft
      survival. By focused microarray analysis we showed this enhanced graft survival
      is associated with increased expression of Foxp3, GITR, CTLA-4 and CCR4 mRNA, all
      genes related to T(reg) cell induction/function, and of Gata3, IL-4, IL-5, IL-13,
      and somewhat surprisingly, of T-bet, INF-gamma and granzyme b. Gene-specific real
      time PCR and immunohistochemistry analysis confirmed an increase in Foxp3(+)
      T(reg) cells in both the skin grafts and draining lymph nodes (DLNs) of CD200(tg)
      recipient mice at both 7/14 days post engraftment, as well as providing evidence
      for increased expression of the ligands for CCR4, CCL17 and CCL22 in both
      locations. Following lentivirus-mediated shRNA treatment of Dox-treated CD200(tg)
      mice to attenuate expression of CCR4 mRNA, the increased localization of T(reg)
      cells in skin/DLN of CD200(tg) recipients was abolished, and the enhanced graft
      survival similarly reversed. We conclude that enhanced CCR4 dependent migration
      of Foxp3(+) T(reg) to grafted tissue and DLNs is an essential step in the graft
      prolongation afforded by overexpression of CD200.

PMID- 21945176
TI  - Immunization with rP22 induces protective immunity against Schistosoma mansoni:
      effects on granuloma down-modulation and cytokine production.
AB  - Schistosomiasis remains a significant public health problem in tropical countries
      and it is recognized as the most important human helminth infection in terms of
      morbidity and mortality. Although the existing antischistosomal drugs are highly
      effective, they do not prevent against reinfection or granuloma formation.
      Therefore, vaccine strategies are essential for the control of schistosomiasis.
      Our group recently identified the recombinant (r) P22 protein, a component of the
      adult worm protein fraction PIII that has been shown to engender protective and
      immunomodulatory effects on murine schistosomiasis. A cDNA clone encoding rP22
      was isolated from a Schistosoma mansoni adult worm cDNA library using anti-PIII
      rabbit serum; it exhibited complete identity with S. mansoni Sm21.7 EF-hand
      antigen. Confocal microscopy revealed that rP22 is a tegument protein localized
      on the surface of S. mansoni miracidia and adult worms. Mice immunized with rP22
      exhibited a 51% and 22.5% decrease in adult worm burden and in hepatic eggs,
      respectively. Additionally, rP22 vaccine produced a reduction in 60% of liver
      granuloma size and 71% of fibrosis in mice, suggesting that rP22 might contribute
      to down-modulate granulomatous hypersensitivity to S. mansoni eggs. Protective
      immunity in mice was associated with high titers of rP22-specific IgG antibodies;
      elevated production of IFN-gamma, TNF-alpha and IL-10; and a reduced level of IL
      4. In conclusion, these findings indicate that rP22-based vaccines could be
      useful to elicit protection and reduce pathology associated to schistosomiasis.

PMID- 21945177
TI  - Association between variation in faecal egg count for a mixed field-challenge of
      nematode parasites and ovine MHC-DQA2 polymorphism.
AB  - The selection of sheep that are resistant to gastrointestinal parasites and have
      lower faecal egg counts (FECs) has been the subject of extensive research. This
      has led to the speculation that the Major Histocompatibility Complex (MHC) genes
      could be used as markers to reduce FEC. In this study, associations between
      variation in ovine MHC-DQA2 and various measures of FEC recorded at two times
      (approximately 4 and 9 months of age) were investigated in a large group of New
      Zealand lambs (n=4676), derived from 185 different sire-lines, of a variety of
      breeds and raised on 25 separate farms. Pair-sample t-tests revealed that FEC for
      Nematodirus spp., Strongyle spp. and total FEC differed significantly between the
      two assessments. A total of twenty one DQA2 alleles or DQA2-DQA2-like haplotypes
      were identified, with allele/haplotype presence and frequency varying
      significantly between farms. For example, allele *0103 was observed on all farms,
      ranging in frequency from 0.2 to 60.9%, while haplotype *0101-*1601 was only
      present on one farm, in two lambs. A number of associations between the
      presence/absence of these alleles and egg counts were observed, but nearly all
      the allelic/haplotypic associations were age and parasite specific, suggesting
      that immune response is both age and challenge (parasite species mix) dependent.
      The exception was allele *1201 which was associated with increased total FECs at
      both 4 and 9 months of age; with it either being, or tending toward being,
      significantly associated with both increased Strongyle spp. and Nematodirus spp.
      counts as well. However, the observed increases in egg counts were small and
      ranged between 5 and 32 eggs per gram. In conclusion, we believe that the MHC
      plays an important role in parasite resistance, but that the MHC-nematode
      interaction is complex and thus the development of a single gene-marker based on
      the "MHC effect" is unlikely.

PMID- 21945178
TI  - Gene transcription analysis in lesional skin of canine epitheliotropic cutaneous
      lymphoma using quantitative real-time RT-PCR.
AB  - Canine epitheliotropic cutaneous lymphoma (cECL) is characterized by infiltration
      of neoplastic lymphocytes in the skin with a specific tropism for the epidermis.
      Migration of lymphocytes is strictly controlled by interactions between
      chemokines and chemokine receptors, which may be involved in the pathogenesis of
      cECL. In this study, we investigated mRNA transcription levels of several
      chemokines (CCL17, CCL19, CCL21, CCL22, CCL27, CCL28 and CXCL10) and chemokine
      receptors (CCR4, CCR7, CCR10 and CXCR3) in lesional skin of cECL by quantitative
      real-time RT-PCR. To examine the subsets of accumulating neoplastic lymphocytes,
      we also investigated transcription levels of type-1 (IFN-gamma, IL-12p35, IL
      12p40 and LT-alpha) and type-2 (IL-4 and IL-13) cytokines and cytotoxic markers
      (perforin and granzyme B). We found that the lesional skin had higher mRNA
      transcription of CCL19, CXCL10, CCR4, CCR7, CCR10 and CXCR3 and lower
      transcription of CCL27 than healthy dog skin (p<0.05). In addition, transcription
      levels of type-1 cytokine and cytotoxic markers in lesional skin were
      significantly higher than those in healthy dog skin. These results indicate that
      the transcription of some chemokines and chemokine receptors, which are necessary
      for skin-homing, epitheliotropism and peripheral segregation of T-cells, is
      upregulated in the lesional skin of cECL. In addition, our results also indicate
      that the subset of neoplastic lymphocytes in cECL is most likely type-1 cytotoxic
      T-cells.

PMID- 21945179
TI  - The Cdc48 machine in endoplasmic reticulum associated protein degradation.
AB  - The AAA-type ATPase Cdc48 (named p97/VCP in mammals) is a molecular machine in
      all eukaryotic cells that transforms ATP hydrolysis into mechanic power to unfold
      and pull proteins against physical forces, which make up a protein's structure
      and hold it in place. From the many cellular processes, Cdc48 is involved in, its
      function in endoplasmic reticulum associated protein degradation (ERAD) is
      understood best. This quality control process for proteins of the secretory
      pathway scans protein folding and discovers misfolded proteins in the endoplasmic
      reticulum (ER), the organelle, destined for folding of these proteins and their
      further delivery to their site of action. Misfolded lumenal and membrane proteins
      of the ER are detected by chaperones and lectins and retro-translocated out of
      the ER for degradation. Here the Cdc48 machinery, recruited to the ER membrane,
      takes over. After polyubiquitylation of the protein substrate, Cdc48 together
      with its dimeric co-factor complex Ufd1-Npl4 pulls the misfolded protein out and
      away from the ER membrane and delivers it to down-stream components for
      degradation by a cytosolic proteinase machine, the proteasome. The known details
      of the Cdc48-Ufd1-Npl4 motor complex triggered process are subject of this review
      article.

PMID- 21945180
TI  - The role of Hsp90 in protein complex assembly.
AB  - Hsp90 is a ubiquitous and essential molecular chaperone that plays central roles
      in many signaling and other cellular pathways. The in vivo and in vitro activity
      of Hsp90 depends on its association with a wide variety of cochaperones and
      cofactors, which form large multi-protein complexes involved in folding client
      proteins. Based on our proteomic work mapping the molecular chaperone interaction
      networks in yeast, especially that of Hsp90, as well as, on experiments and
      results presented in the published literature, one major role of Hsp90 appears to
      be the promotion and maintenance of proper assembly of protein complexes. To
      highlight this role of Hsp90, the effect of the chaperone on the assembly of the
      following seven complexes is discussed in this review: snoRNP, RNA polymerase II,
      phosphatidylinositol-3 kinase-related protein kinase (PIKK), telomere complex,
      kinetochore, RNA induced silencing complexes (RISC), and 26S proteasome. For some
      complexes, it is observed that Hsp90 mediates complex assembly by stabilizing an
      unstable protein subunit and facilitating its incorporation into the complex; for
      other complexes, Hsp90 promotes change in the composition of that complex. In all
      cases, Hsp90 does not appear to be part of the final assembled complex. This
      article is part of a Special Issue entitled:Heat Shock Protein 90 (HSP90).

PMID- 21945181
TI  - Clathrin-mediated endocytosis: the gateway into plant cells.
AB  - Endocytosis in plants has an essential role not only for basic cellular functions
      but also for growth and development, hormonal signaling and communication with
      the environment including nutrient delivery, toxin avoidance, and pathogen
      defense. The major endocytic mechanism in plants depends on the coat protein
      clathrin. It starts by clathrin-coated vesicle formation at the plasma membrane,
      where specific cargoes are recognized and packaged for internalization. Recently,
      genetic, biochemical and advanced microscopy studies provided initial insights
      into mechanisms and roles of clathrin-mediated endocytosis in plants. Here we
      summarize the present state of knowledge and compare mechanisms of clathrin
      mediated endocytosis in plants with animal and yeast paradigms as well as review
      plant-specific regulations and roles of this process.

PMID- 21945182
TI  - Validation of a predictive survival model in Italian patients with cystic
      fibrosis.
AB  - BACKGROUND: In 2001 Liou published a 5-year survival model using CFF Registry
      data. AIMS: To evaluate its validity in predicting survival in Italian CF
      patients. METHODS: In a retrospective study on 945 patients, the 9 variables
      selected by Liou were analyzed, vital status on December 2008 recorded and
      observed and expected deaths compared. To develop a new model, patients were
      randomly divided into a derivation (n=475) and a validation sample (n=470).
      RESULTS: A significant difference was found between observed and expected deaths
      based on Liou's model (62 vs 94), with a 34% reduction in mortality (p<0.05). A
      new model (based on FEV1, Staphylococcus aureus and Burkholderia cepacia complex
      infection, number of pulmonary exacerbations/year) was generated, that correctly
      predicted survival in the validation sample (31 observed vs 29 expected deaths,
      p=0.660). CONCLUSIONS: The Liou model did not adequately predict 5-year survival
      in our CF population that, compared to the one in which it was originally tested,
      could benefit from 10 years of improvement in treatments and practice patterns. A
      new generated model, based on only four variables, was more accurate in
      predicting 5-year survival in Italian CF patients.

PMID- 21945183
TI  - Dual targeting folate-conjugated hyaluronic acid polymeric micelles for
      paclitaxel delivery.
AB  - A series of novel self-assembled hyaluronic acid derivatives (HA-C(18)) grafted
      with hydrophobic octadecyl moiety and further dual targeting folic acid
      conjugated HA-C(18) (FA-HA-C(18)) were synthesized. With the increase in the
      degree of substitution of octadecyl group from 12.7% to 19.3%, the critical
      micellar concentration of HA-C(18) copolymers decreased from 37.3 to 10.0 MUg/mL.
      Paclitaxel (PTX) was successfully encapsulated into the hydrophobic cores of the
      HA-C(18) and FA-HA-C(18) micelles, with encapsulation efficiency as high as
      97.3%. The physicochemical properties of the polymeric micelles were measured by
      DLS, TEM and DSC. Moreover, in vitro release behavior of PTX was investigated by
      dialysis bag method and PTX was released from micelles in a near zero-order
      sustained manner. In vitro antitumor activity tests suggested PTX-loaded HA-C(18)
      and FA-HA-C(18) micelles exhibited significantly higher cytotoxic activity
      against MCF-7 and A549 cells compared to Taxol at a lower PTX concentration. The
      cellular uptake experiments were conducted by quantitative assay of PTX cellular
      accumulation and confocal laser scanning microscopy imaging of coumarin-6 labeled
      HA-C(18) and FA-HA-C(18) micelles in folate receptor overexpressing MCF-7 cells.
      Folate and CD44 receptor competitive inhibition studies performed by fluorescence
      microscopy imaging suggested intracellular delivery of HA-C(18) and FA-HA-C(18)
      micelles were efficiently taken up via CD44 receptor-mediated endocytosis. The
      folate receptor-mediated endocytosis further enhanced internalized amounts of FA
      HA-C(18) micelles in MCF-7 cells, as compared with HA-C(18) micelles. The
      internalization pathways of PTX-loaded HA-C(18) and FA-HA-C(18) micelles might
      include clathrin-mediated endocytosis, caveolae-mediated endocytosis and
      macropinocytosis. Therefore, the present study suggested that HA-C(18) and FA-HA
      C(18) copolymers as biodegradable, biocompatible and cell-specific targetable
      nanostructure carriers, are promising nanosystems for cellular and intracellular
      targeting delivery of hydrophobic anticancer drugs.

PMID- 21945184
TI  - Molecular mechanism study of chemosensitization of doxorubicin-resistant human
      myelogenous leukemia cells induced by a composite polymer micelle.
AB  - The present study was aimed to overcome the multidrug resistance (MDR) of tumor
      cells which accounts for the failure of clinical chemotherapy. A novel
      doxorubicin (DOX)-loaded composite micelle consisting of polyethylene glycol
      (PEG)-polycaprolactone (PCL)/Pluronic P105 has been developed and was proved to
      inhibit the drug resistance of human myelogenous leukemia (K562/ADR) cells. The
      modulation mechanism that DOX-loaded the composite micelle inhibited MDR was for
      the first time investigated at cell levels. Results indicated that the
      cytotoxicity in K562/ADR cells treated by DOX-loaded PEG-PCL/P105 composite
      micelle was about 4 times higher than DOX solution at 12 MUg/mL of DOX. Confocal
      images showed that the DOX-loaded composite micelles gradually entered into
      cytoplasm and nucleus, and stayed in intracellular much longer than DOX solution.
      All the micelles (PEG-PCL micelle, P105 micelle and PEG-PCL/P105 composite
      micelle) did not change Pgp expression on the surface of K562/ADR cells. However,
      further study revealed that micelle containing of P105 (P105 or PEG-PCL/P105
      composite micelle) significantly decreased ATP level, and consequently restricted
      the activity of Pgp by down-regulation of mitochondrial membrane potential. On
      the other hand, the PEG-PCL micelle had no effect on both mitochondrial membrane
      potential and ATP level of the K562/ADR cells, but its access to K562/ADR cells
      through endocytic pathway avoided the recognition of Pgp. The PEG-PCL/P105
      composite micelle was designed based on the combination of P105-mediated down
      regulation of mitochondrial membrane potential the malignant cells and PEG-PCL
      mediated internalization effect. Therefore, the novel composite micelle is a
      promising drug delivery system for anticancer drug to overcome MDR.

PMID- 21945185
TI  - Liposome formulated with TAT-modified cholesterol for improving brain delivery
      and therapeutic efficacy on brain glioma in animals.
AB  - The treatment of central nervous system diseases such as brain glioma is a major
      challenge due to the presence of the blood-brain barrier (BBB). A cell
      penetrating peptide TAT (AYGRKKRRQRRR), which appears to enter cells with
      alacrity, was employed to enhance the delivery efficiency of normal drug
      formulation to the brain. Targeting liposomal formulations often apply modified
      phospholipids as anchors. However, cholesterol, another liposomal component more
      stable and cheaper, has not been fully investigated as an alternative anchor. In
      our study, TAT was covalently conjugated with cholesterol for preparing
      doxorubicin-loaded liposome for brain glioma therapy. Cellular uptake by brain
      capillary endothelial cells (BCECs) and C6 glioma cells was explored. The anti
      proliferative activity against C6s confirmed strong inhibitory effect of the
      liposomes modified with doxorubicin-loaded TAT. The bio-distribution findings in
      brains and hearts were evident of higher efficiency of brain delivery and lower
      cardiotoxic risk. The results on survival of the brain glioma-bearing animals
      indicate that survival time of the glioma-bearing rats treated with TAT-modified
      liposome was much longer than in the other groups. In conclusion, the potency of
      the TAT-modified liposome to enter the BBB appears to be related with the TAT on
      the liposome's surface. The TAT-modified liposome may improve the therapeutic
      efficacy on brain glioma in vitro and in vivo.

PMID- 21945186
TI  - The biogeochemical reactivity of suspended particulate matter at nested sites in
      the Dee basin, NE Scotland.
AB  - Variation in the organic matter content associated with suspended particulate
      matter (SPM) is an often overlooked component of carbon cycling within freshwater
      riverine systems. The potential biogeochemical reactivity of particulate organic
      carbon (POC) that affect its interactions and fate, i.e. respired and lost to the
      atmosphere along river continua or ultimately exported to estuarine and oceanic
      pools was assessed. Eleven contrasting sites draining nested catchments (5-1837
      km(2)) in the River Dee basin, NE Scotland were sampled during summer 2008 to
      evaluate spatio-temporal variations in quantity and quality (biogeochemical
      reactivity) of SPM during relatively low flow conditions. Mean SPM concentrations
      increased from 0.21 to 1.22 mg L(-1) between the uppermost and lowest mainstem
      sites. Individually, POC concentrations ranged from 0.08 to 0.55 mg L(-1) and
      accounted for ca. 3-15% of total aqueous organic carbon transported. The POC
      content was partitioned into autotrophic (2.78-73.0 mg C g(-1) SPM) and detrital
      (119-388 mg C g(-1) SPM) biomass carbon content. The particulate respired CO(2)-C
      as a % of the total carbon associated with SPM, measured by MicroRespTM over 18
      h, varied in recalcitrance from 0.49% at peat-dominated sites to 3.20% at the
      lowermost mainstem site. Significant (p<0.05) relationships were observed between
      SPM biogeochemical reactivity measures (% respired CO(2)-C; chlorophyll alpha;
      bioavailable-phosphorus) and arable and improved grassland area, associated with
      increasing biological productivity downstream. Compositional characteristics and
      in-stream processing of SPM appear to be related to contributory land use
      pressures, that influence SPM characteristics and biogeochemistry (C:N:P
      stoichiometry) of its surrounding aqueous environment. As moorland influences
      declined, nutrient inputs from arable and improved grasslands increasingly
      affected the biogeochemical content and reactivity of both dissolved and
      particulate matter. This increases the potential for recycling of the organic
      matter that is either transported from upstream or entering further along the
      riverine continuum.

PMID- 21945187
TI  - Chemical and structural composition of Atlantic Canadian moose (Alces alces)
      incisors with patterns of high breakage.
AB  - Analysis of mammalian teeth can provide information regarding local environmental
      conditions. For example, a high incidence of breakage and wear within a
      population may indicate poor food quality. Individuals consuming a diet causing
      high mechanical stress on their teeth, and/or lacking the appropriate minerals
      for proper development, could experience degradation of tooth condition.
      Previously, we documented a high rate of incisor tooth breakage, with age, in two
      genetically distinct moose populations in Atlantic Canada. In this study, multi
      element (11B, 63Cu, 64Zn, 75As, 85Rb, 88Sr, 111Cd, 118Sn, 137Ba, 208Pb, 232Th,
      and 238U) analyses using laser ablation ICP-MS were performed on moose incisors
      from multiple North American regions. The purpose was to determine whether the
      elemental composition of moose incisors varies among regions, and whether that
      variation is related to tooth degradation among Atlantic Canadian populations. A
      principal components analysis revealed that nearly 50% of the elemental variation
      in the inner enamel matrix of moose teeth was explained by three groupings of
      elements. The element groupings revealed differences among geographic regions,
      but did not explain the variation between incisors that were broken and those
      that were not. Regression models indicate that the elemental group which includes
      Cu, Pb, and Zn is related to decreases in incisal integrity. It is likely that
      other environmental factors contribute to the occurrence of increased incisor
      breakage in affected populations. The relationship between food resource quantity
      and quality, as a function of moose density, is hypothesized to explain loss of
      tooth integrity.

PMID- 21945188
TI  - Competitive adsorptions of nitrile hydratase and amidase on polyacrylonitrile and
      its effect on surface modification.
AB  - In this study, enzymatic surface modification of polyacrylonitrile was studied
      using nitrile metabolizing enzyme of Amycolatopsis sp. IITR 215. During enzymatic
      treatment of polyacrylonitrile at pH of 5.8 and 7, it was observed that the
      conversion of cyano group to carboxylic acid at pH 5.8 was three times higher
      than at pH 7. This difference in enzymatic treatment efficiency was explained by
      studying the differences in adsorption profiles of nitrile hydratase and amidase
      on polyacrylonitrile at pH of 5.8 and 7. Adsorption profiles were determined by
      monitoring the unbound activities of these two enzymes in the supernatant. From
      the specific activity profiles of bound nitrile hydratase and amidase it was
      concluded that more specific binding of nitrile hydratase was observed at pH 5.8
      as compared to pH 7. In case of amidase, optimum adsorption was obtained at pH
      5.8 within 5h whereas in case of pH 7 it was obtained within 20 h. Thus at pH 7,
      sequential adsorption of nitrile hydratase and amidase was observed and this
      adsorption profile was similar to the Vroman effect reported during plasma
      protein adsorption at solid-liquid interface. Ideally, specific nitrile hydratase
      adsorption followed by sequential adsorption of amidase may enhance higher
      conversion of cyano group to carboxylic acid.

PMID- 21945189
TI  - A European survey relating to cancer therapy and neutropenic infections: nurse
      and patient viewpoints.
AB  - PURPOSE: Severe neutropenia and febrile neutropenia (FN) are the major causes of
      morbidity, treatment interruptions and dose reductions in patients undergoing
      chemotherapy. The European Oncology Nursing Society (EONS) conducted an European
      survey to evaluate nurse perspectives on prevention of infection and FN in this
      setting, and how much they educate their patients about this. A separate survey
      explored these issues in patients receiving chemotherapy. METHODS: 217 nurse
      participants were identified by EONS from the membership database and 473 cancer
      patients who were receiving/had received chemotherapy were identified through
      patient advocacy groups. Questionnaires were completed anonymously online for
      both surveys. RESULTS: More than 90% of the nurses agreed that preventing
      infections including FN is extremely/very important for a successful chemotherapy
      outcome and said that they, or other health professionals in their practice,
      advised patients about these issues. Most (90%) indicated that they favoured
      giving treatment to protect against FN and infections in chemotherapy patients at
      risk, rather than treating infection after it develops, but 82% expressed concern
      over patient concordance with measures employed. A substantial proportion of
      patients reported emergency room visits, hospitalization and/or chemotherapy
      delays or changes as a result of neutropenia, infection or FN. However, only 44%
      said that their infection risk was discussed with them before starting
      chemotherapy. CONCLUSIONS: Our findings indicate that nurses recognise the
      importance of reducing the risk of infection and FN in patients undergoing
      chemotherapy, as well as the need to educate patients. However, results of the
      patient survey suggest a need for better patient education.

PMID- 21945190
TI  - Quality of life in children and adolescents surviving cancer.
AB  - PURPOSE: To explore subjective and proxy reported QoL (Quality of Life) in
      children and adolescents surviving cancer three years after diagnosis compared
      with healthy controls. METHOD: Case-control study including 50 children and
      adolescents diagnosed with cancer between January 1, 1993 and January 1, 2003 and
      treated at the Paediatric Department of St. Olav's University Hospital in
      Trondheim, Norway. Data were collected using The Inventory of Life Quality in
      Children and Adolescents (ILC) and the KINDL QoL questionnaires (parent and self
      reports), as well as by collecting data for any somatic late effects and
      psychological problems from the medical records of children surviving cancer.
      RESULTS: Adolescents surviving cancer as a group assessed their QoL as similar to
      that of their peers. However, adolescents surviving brain tumours or those with
      late effects reported lower QoL and an increased number of QoL domains perceived
      as problematic, even many years after diagnosis and treatment. Parents generally
      report a poorer QoL for their children surviving cancer and a greater number of
      QoL domains experienced as problematic compared with parent controls. CONCLUSION:
      To improve the child's total functioning and well-being we conclude that when
      planning long-term follow-up care, rehabilitation of children and adolescents
      with cancer, especially for survivors with brain tumours, and with late effects
      should particularly take into account their subjectively perceived and proxy
      reported QoL, in addition to their psychological problems and psychosocial
      functioning.

PMID- 21945191
TI  - Expression profile of the sphingosine kinase signalling system in the lung of
      patients with chronic obstructive pulmonary disease.
AB  - AIMS: Chronic obstructive pulmonary disease (COPD) is a leading cause of death
      worldwide. Despite its importance, treatment methods are limited and restricted
      to symptomatic care, highlighting the urgent need for new treatment options.
      Tissue damage in COPD is thought to result from an inability of the normal repair
      processes with accumulation of apoptotic material and impaired clearance of this
      material by macrophages in the airways. Lung inflammation involves the bioactive
      sphingolipid sphingosine 1-phosphate (S1P). MAIN METHODS: We investigated lung
      tissue samples from 55 patients (25 with COPD) undergoing lobectomies for
      management of cancer. We analysed the sphingosine-kinase (SphK) mRNA expression
      profile, SphK enzyme activity as well as the localisation and expression of
      individual proteins related to the SphK-signalling system. KEY FINDINGS: We show
      in this study for the first time a comprehensive expression profile of all
      synthesising enzymes, receptors and degrading enzymes of the SphK-signalling
      system in the human lung. Multivariate ANOVA showed that the relative mRNA
      expression of S1P receptor (S1PR) subtype 5 was reduced in COPD. There were
      strong positive correlations between the mRNA expression of S1PR5 and S1PR1 and
      S1PR3, and between S1PR3 and S1PR2. A significant negative correlation was found
      between S1PR1 and SphK protein activity. SIGNIFICANCE: The correlations between
      expression levels of receptors and enzymes involved in the sphingosine kinase
      signalling system in the lung suggest common regulatory mechanisms. Our findings
      of reduced S1PR5 in COPD and the correlation with other S1P receptors in COPD
      identify S1PR5 as a possible novel target for pharmacotherapy.

PMID- 21945192
TI  - Oleuropein and hydroxytyrosol inhibit adipocyte differentiation in 3 T3-L1 cells.
AB  - AIMS: Oleuropein and hydroxytyrosol, which are antioxidant molecules found in
      olive leaves and oil, have been reported to exert several biochemical and
      pharmacological effects. These polyphenols are able to prevent low-density
      lipoprotein oxidation and protect cells against several diseases. Here, we
      studied the effect of these compounds on adipocyte differentiation in 3 T3-L1.
      MAIN METHODS: To perform this study, 3 T3-L1 preadipocytes viability was analysed
      via Trypan blue and MTT assays, and triglycerides were stained with Oil Red O.
      Adipogenesis related genes expression were checked by RT-PCR and qRT-PCR. Also,
      cells counting and flow cytometry were used to analyse the mitotic cell cycle
      during the adipogenesis clonal expansion phase. RESULTS: Oleuropein and
      hydroxytyrosol dose-dependently suppressed intracellular triglyceride
      accumulation during adipocyte differentiation without effect on cell viability.
      PPARgamma, C/EBPalpha and SREBP-1c transcription factors and their downstream
      targets genes (GLUT4, CD36 and FASN) were down-regulated after treatment by
      oleuropein and hydroxytyrosol. At 200 and 300 MUmol/L oleuropein or 100 and 150
      MUmol/L hydroxytyrosol, the greatest effect on the adipogenesis process was
      observed during the early stages of differentiation. Flow cytometry revealed both
      polyphenols to inhibit the division of 3T3-L1 preadipocytes during mitotic clonal
      expansion and cause cell cycle delay. Furthermore, oleuropein and its derivate
      hydroxytyrosol decreased the transcriptional activity of SREBP-1c in a stable
      transfected 3T3-L1 cell line. SIGNIFICANCE: These findings indicate that both
      compounds are able to prevent 3T3-L1 differentiation by inhibition of the mitotic
      clonal expansion and downregulation of the adipogenesis related genes.

PMID- 21945194
TI  - Thumb tip flexion test.

PMID- 21945195
TI  - No clock to rule them all.
AB  - This article introduces general concepts and definitions related to the notion of
      asynchronous computation in the framework of artificial neural networks. Using
      the dynamic field theory as an illustrative example, we explain why one may want
      to perform such asynchronous computation and how one can implement it since this
      computational scheme draws several consequences on both the trajectories and the
      stability of the whole system. After giving an unequivocal definition of
      asynchronous computation, we present a few practically usable methods and
      quantitative bounds that can guarantee most of the mesoscopic properties of the
      system.

PMID- 21945193
TI  - A survey of psychosis risk symptoms in Kenya.
AB  - Defining the prepsychotic state in an effort to prevent illness progression and
      the development of disorders such as schizophrenia is a rapidly growing area of
      psychiatry. The presentation of psychotic symptoms can be influenced by culture;
      however, there has not been any previous assessment of psychosis risk symptoms in
      the continent of Africa. Our study aimed to measure the prevalence of psychosis
      risk in a community sample in Nairobi, Kenya, and to evaluate the effects of key
      demographic variables. A culturally modified version of the 12-item PRIME-Screen
      (mPRIME) was self-administered by 2758 youth (aged 14-29 years) recruited through
      house-to-house visits in Nairobi, Kenya. The prevalence and severity of psychosis
      risk items from the mPRIME and the effects of sex and age on symptoms were
      evaluated. k-Means cluster analysis was used to identify symptom groups.
      Depending on the mPRIME item, 1.8% to 19.5% of participants reported certainty of
      having had a psychosis risk symptom. Overall, 45.5% reported having had any
      psychosis risk symptom. Females had a significantly higher mean severity score on
      items evaluating persecutory ideation and auditory hallucinations. Symptom
      severity on 5 items showed a modest (R = 0.09-0.13) but significant correlation
      with age. Cluster analysis identified 4 groups of participants: normative (55%),
      high symptom (11%), intermediate symptom (19%), and grandiose symptom (15%).
      Psychosis risk symptoms appear to be highly prevalent in Kenyan youth.
      Longitudinal studies are needed to determine the correlation of identified
      symptoms with transition to psychotic illness, as well as the associated
      functionality and distress, to develop appropriate intervention strategies.

PMID- 21945196
TI  - Evaluation of columns packed with shell particles with compounds of
      pharmaceutical interest.
AB  - The commercial C18 columns packed with sub-3 MUm shell particles were tested and
      compared to a reference UHPLC column, in terms of kinetic performance as well as
      selectivity, retention capability, peak shape and loading capacity. For this
      purpose, a set of pharmaceutically relevant molecules was selected, including
      acidic, neutral and basic drugs. Regarding kinetic performance, h(opt) values for
      the shell particles were found between 1.7 and 2, while the UHPLC column provided
      a value of approximately 2.5. However, this impressive performance should be
      considered with caution, particularly for the construction of kinetic plots since
      h(opt) values were sometimes related to the column dimensions, depending on the
      provider (h(opt) comprised between 1.8 and 2.6 for longer columns of 150 mm
      packed with shell particles). Despite the non-porous inner core of the shell
      particles representing between 25 and 36% of the particle, we demonstrated that
      the decrease in retention was on the maximum equal to 15% for Ascentis column
      while Acquity and Poroshell were strictly equivalent in terms of retention.
      Concerning loading capacity, it remains comparable to that of fully porous sub-2
      MUm particles and always more pronounced with 0.1% formic acid vs. phosphate
      buffer. The loading capacity of the different columns was found to be better
      correlated to the pore volume or surface coverage than the shell thickness.
      Experimentally, the most pronounced overloading was observed with the Poroshell.
      Finally, the selectivity and peak shape were evaluated using a mixture of basic
      and acidic drugs. It appears that results were very similar between sub-3 MUm
      shell particles and fully porous sub-2-MUm particles for our mixture of
      compounds, showing the ability to transfer existing methods to shell particles,
      with only limited adjustments. This study confirms the potential of columns
      packed with shell particles and demonstrates the interest of such column
      technology with pharmaceutical compounds.

PMID- 21945197
TI  - Silver-cemented frit formation for the stabilization of the packing structure in
      the microchannel of electrochromatographic microchips.
AB  - A simple but effective frit formation technique was developed to stabilize the
      packing structure inside the microchannel of capillary electrochromatographic
      microchips, utilizing the electroless plating technique. A Ag(NH(3))(2)(+)
      solution was allowed to diffuse through the colloidal silica packing in the
      microchannel from the reservoir of the microchip for a limited amount of time,
      and then it was reduced by an excess amount of formaldehyde solution. A frit
      structure of ~70 MUm in length was formed at the entrance of the microchannel
      without clogging when treated with 1mM Ag(NH(3))(2)(+) ion and formaldehyde for
      30s and 150 s, respectively. The formation of the frit structure was confirmed by
      a scanning electron microscopy. The stability of the packing structure was tested
      rigorously and then confirmed by applying alternating electroosmotic flows back
      and forth with pulsed potential steps on both sides of the frit structure. The
      effect of the treatment on the electrochromatograms was evaluated after the
      microchips were repeatedly used and stored for a long period of time. The results
      indicated that the silver-cemented frit structure extended the lifetime of the
      fully packed CEC microchips distinctly.

PMID- 21945199
TI  - Optimization of pacing after cardiopulmonary bypass.

PMID- 21945198
TI  - Analyzing histamine release by flow cytometry (HistaFlow): a novel instrument to
      study the degranulation patterns of basophils.
AB  - BACKGROUND: Stimulated human basophils exhibit different degranulation patterns
      with release of mediators and appearance of activation markers such as CD63 and
      CD203c. Traditionally, released mediators are quantified in the supernatant of
      activated cells, whereas the expression of activation markers by individual cells
      is analyzed by flow cytometry. Alternatively, intracellular histamine and its
      release by basophils and mast cells have been repeatedly studied applying an
      enzyme-affinity-gold method based on the affinity of the histaminase diamine
      oxidase for its substrate histamine. OBJECTIVE: To develop a flow cytometric
      technique enabling to study histamine release by individual basophils in
      combination with the expression of activation markers. To elucidate the
      principles of basophil degranulation on a single cell level. METHODS:
      Intracellular histamine and its release is analyzed flow cytometrically by an
      enzyme-affinity method using diamine oxidase conjugated to laser-excitable
      fluorochromes. Phenotyping of cells implied flow cytometric quantification of
      CD63 and CD203c. Stimuli such as allergen, anti-IgE, N-formyl-met-leu-phe (fMLP),
      phorbol 12-myristate 13-acetate (PMA), ionomycin and interleukin (IL-)3 are
      applied to obtain different degranulation profiles. RESULTS: Stimulation with
      anti-IgE, allergen, fMLP and PMA+/-ionomycin induces a rapid release of histamine
      that can be analyzed flow cytometrically. Analyses on a single cell level reveal
      that histamine release is not restricted to cells showing significant up
      regulation of CD63. Alternatively, up-regulation of CD203c does not per se
      indicate histamine release. In some patients, priming of cells with IL-3 not only
      facilitates basophil responsiveness but also implies an increased ability of DAO
      to label the cells. CONCLUSION: This study provides the proof-of-concept that
      histamine and its release can be studied by multicolor flow cytometry on a single
      cell level (HistaFlow). Coupling the data to simultaneous phenotyping of
      activated basophils confirms that histamine release principally results from
      anaphylactic degranulation and in a lesser extent from piecemeal degranulation.

PMID- 21945200
TI  - Inferior colliculus contributions to phase encoding of stop consonants in an
      animal model.
AB  - The human auditory brainstem is known to be exquisitely sensitive to fine-grained
      spectro-temporal differences between speech sound contrasts, and the ability of
      the brainstem to discriminate between these contrasts is important for speech
      perception. Recent work has described a novel method for translating brainstem
      timing differences in response to speech contrasts into frequency-specific phase
      differentials. Results from this method have shown that the human brainstem
      response is surprisingly sensitive to phase differences inherent to the stimuli
      across a wide extent of the spectrum. Here we use an animal model of the auditory
      brainstem to examine whether the stimulus-specific phase signatures measured in
      human brainstem responses represent an epiphenomenon associated with far-field
      (i.e., scalp-recorded) measurement of neural activity, or alternatively whether
      these specific activity patterns are also evident in auditory nuclei that
      contribute to the scalp-recorded response, thereby representing a more
      fundamental temporal processing phenomenon. Responses in anaesthetized guinea
      pigs to three minimally-contrasting consonant-vowel stimuli were collected
      simultaneously from the cortical surface vertex and directly from central nucleus
      of the inferior colliculus (ICc), measuring volume conducted neural activity and
      multiunit, near-field activity, respectively. Guinea pig surface responses were
      similar to human scalp-recorded responses to identical stimuli in gross
      morphology as well as phase characteristics. Moreover, surface-recorded
      potentials shared many phase characteristics with near-field ICc activity.
      Response phase differences were prominent during formant transition periods,
      reflecting spectro-temporal differences between syllables, and showed more subtle
      differences during the identical steady state periods. ICc encoded stimulus
      distinctions over a broader frequency range, with differences apparent in the
      highest frequency ranges analyzed, up to 3000 Hz. Based on the similarity of
      phase encoding across sites, and the consistency and sensitivity of response
      phase measured within ICc, results suggest that a general property of the
      auditory system is a high degree of sensitivity to fine-grained phase information
      inherent to complex acoustical stimuli. Furthermore, results suggest that
      temporal encoding in ICc contributes to temporal features measured in speech
      evoked scalp-recorded responses.

PMID- 21945201
TI  - Neuroimaging in acute liver failure.
AB  - Acute liver failure (ALF) is frequently complicated by the development of brain
      edema that can lead to intracranial hypertension and severe brain injury.
      Neuroimaging techniques allow a none-invasive assessment of brain tissue and
      cerebral hemodynamics by means of transcranial Doppler ultrasonography, magnetic
      resonance and nuclear imaging with radioligands. These methods have been very
      helpful to unravel the pathogenesis of this process and have been applied to
      patients and experimental models. They allow monitoring the outcome of patients
      with ALF and neurological manifestations. The increase in brain water can be
      detected by observing changes in brain volume and disturbances in diffusion
      weighted imaging. Neurometabolic changes are detected by magnetic resonance
      spectroscopy, which provides a pattern of abnormalities characterized by an
      increase in glutamine and a decrease in myo-inositol. Disturbances in cerebral
      blood flow are depicted by SPECT or PET and can be monitored and the bedside by
      assessing the characteristics of the waveform provided by transcranial Doppler
      ultrasonography. Neuroimaging methods, which are rapidly evolving, will
      undoubtedly lead to future diagnostic and therapeutic progress that could be very
      helpful for patients with ALF.

PMID- 21945202
TI  - Neuroprotective effect of naringin, a dietary flavonoid against 3-nitropropionic
      acid-induced neuronal apoptosis.
AB  - The aim of this study was to investigate the protective effect of naringin, a
      flavonoid on 3-Nitropropionic acid (3-NP)-induced neurodegeneration through the
      modulation of intrinsic apoptotic cascade in Wistar rats. 3-NP is an irreversible
      inhibitor of complex II in the mitochondria. 3-NP-induced neurodegeneration has
      been widely used as an animal model of Huntington's disease (HD). Increased
      oxidative stress is one of the major deleterious events in 3-NP-induced neuronal
      apoptosis. Rats administered with 3-NP showed increase in the levels of lipid
      peroxidation and protein carbonyl, which was significantly decreased upon
      naringin treatment (80 mg/kg body weight). 3-NP-induced rats showed decrease in
      the activities of enzymic antioxidants and reduced levels of non-enzymic
      antioxidants. Naringin treatment ameliorated the antioxidant status by increasing
      the activities of enzymic antioxidants and the levels of non-enzymatic
      antioxidants. 3-NP-induced rats showed decrease in the activities of ATPases in
      striatum, which was restored to normal level upon naringin treatment.
      Histopathological observation of the striatal tissue showed protective role of
      naringin in 3-NP-induced rats. Naringin also reduced the 3-NP-induced apoptosis
      via decrease in the cytochrome c release from mitochondria and caspase 3
      activation as revealed by Western blot. Naringin treatment also decreased the
      expressions of pro-apoptotic markers like Bad and Bax. Further, naringin
      antagonized 3-NP-induced decrease in Bcl-2 mRNA expression. The results of this
      study show evidence on the neuroprotective effect of naringin against 3-NP
      induced neuronal apoptosis through its antioxidant and anti-apoptotic effects.

PMID- 21945203
TI  - Design and synthesis of biotinylated DHMEQ for direct identification of its
      target NF-kappaB components.
AB  - The design and synthesis of dehydroxymethylepoxyquinomicin (DHMEQ) derivatives
      were carried out to investigate the intracellular targets. The synthetic biotin
      probe exhibited membrane permeability and combined selectively with the target
      protein p65.

PMID- 21945204
TI  - The behavior of kinetic parameters in production of pectinase and xylanase by
      solid-state fermentation.
AB  - Solid-state fermentation (SSF) is defined as the growth of microbes without a
      free-flowing aqueous phase. The feasibility of using a citrus peel for producing
      pectinase and xylanase via the SSF process by Aspergillus niger F3 was evaluated
      in a 2 kg bioreactor. Different aeration conditions were tested to optimize the
      pectinase and xylanase production. The best air flow intensity was 1 V kg M
      (volumetric air flow per kilogram of medium), which allowed a sufficient amount
      of O2 for the microorganism growth producing 265 U/g and 65 U/g pectinases and
      xylanases, respectively. A mathematical model was applied to determine the
      different kinetic parameters related to SSF. The specific growth rate and biomass
      oxygen yield decreased during fermentation, whereas an increase in the
      maintenance coefficient for the different employed carbon sources was
      concurrently observed.

PMID- 21945205
TI  - Overproduction of alkaline polygalacturonate lyase in recombinant Escherichia
      coli by a two-stage glycerol feeding approach.
AB  - This work aims to achieve the overproduction of alkaline polygalacturonate lyase
      (PGL) with recombinant Escherichia coli by a two-stage glycerol feeding approach.
      First, the PGL coding gene from Bacillus subtilis WSHB04-02 was expressed in E.
      coli BL21 (DE3) under the strong inducible T7 promoter of the pET20b (+) vector.
      And then the influence of media composition, induction temperature, and inducer
      isopropyl beta-D-1-thiogalactopyranoside (IPTG) concentration on cell growth and
      PGL production was investigated. Finally, a two-stage glycerol feeding strategy
      was proposed and applied in a 3-L fermenter, where cultivation was conducted at a
      controlled specific growth rate (MUset=0.2) during pre-induction phase, followed
      by a constant glycerol feeding rate of 12 ml h(-1) at post-induction phase. The
      total PGL yield reached 371.86 U mL(-1), which is the highest PGL production by
      recombinant E. coli expression system.

PMID- 21945206
TI  - Production of phytase under solid-state fermentation using Rhizopus oryzae: novel
      strain improvement approach and studies on purification and characterization.
AB  - Present study introduces linseed oil cake as a novel substrate for phytase
      production by Rhizopus oryzae. Statistical approach was employed to optimize
      various medium components under solid state fermentation (SSF). An overall 8.41
      fold increase in phytase production was achieved at the optimum concentrations
      (w/w, mannitol, 2.05%; ammonium sulfate, 2.84% and phosphate, 0.38%). Further
      enhancement by 59% was observed due to a novel strain improvement approach.
      Purified phytase (~34 kDa) showed optimal temperature of 45  degrees C, dual pH
      optima at 1.5 and 5.5 and possesses high catalytic efficiency (2.38*10(6) M(-1)
      s(-1)). Characterization study demonstrates the phytase as highly thermostable
      and resistant to proteolysis, heavy metal ions, etc. Furthermore, an improved
      HPLC method was introduced to confirm the ability of phytase to degrade phytic
      acid completely and was found to be an efficient method.

PMID- 21945207
TI  - Excess sludge reduction by biological way: from experimental experience to a real
      full scale application.
AB  - The aim of this study was to investigate the ability of a biological process
      applied in the sludge line and based on the alternation of oxic and anoxic
      phases, to minimize the waste sludge production. After some tests in pilot scale,
      the process was applied in a real municipal wastewater treatment plant of 35,000
      PE trying out one setting of working experimental conditions. A rate of the
      recycle flow was conditioned in a treatment basin, maintaining an HRT of 10 days.
      The control device operated for the 50% of time in the ORP range between -400 and
      -200 mV, and for the 50% in the ORP range between -200 and +50 mV. The mass
      balance defined an actual observed growth yield equal to 0.09 kgTVSkgCODr(-1),
      and the heterotrophic yield values, assessed by batch tests, seemed to be a
      suitable marker for the sludge reduction and for the energy uncoupling.

PMID- 21945208
TI  - Production of (2S,3S)-2,3-butanediol and (3S)-acetoin from glucose using resting
      cells of Klebsiella pneumonia and Bacillus subtilis.
AB  - Production of highly pure (2S,3S)-2,3-butanediol ((2S,3S)-2,3-BD) and (3S)
      acetoin ((3S)-AC) in high concentrations is desirable but difficult to achieve.
      In the present study, glucose was first transformed to a mixture of (2S,3S)-2,3
      BD and meso-2,3-BD by resting cells of Klebsiella pneumoniae CICC 10011, followed
      by biocatalytic resolution of the mixture by resting cells of Bacillus subtilis
      168. meso-2,3-BD was transformed to (3S)-AC, leaving (2S,3S)-2,3-BD in the
      reaction medium. Using this approach, 12.5 g l(-1) (2S,3S)-2,3-BD and 56.7 g l(
      1) (3S)-AC were produced. Stereoisomeric purity of (2S,3S)-2,3-BD and
      enantiomeric excess of (3S)-AC was 96.9 and 96.2%, respectively.

PMID- 21945209
TI  - H2S gas biological removal efficiency and bacterial community diversity in
      biofilter treating wastewater odor.
AB  - The objective of this study was to assess the feasibility of using a biofilter
      system to treat hydrogen sulfide (H2S) contaminated air and to characterize its
      microbial community. The biofilter system was packed with peat. During the
      experimental work, the peat was divided in three layers (down, middle, and up).
      Satisfactory removal efficiencies of H2S were proved and reached 99% for the
      majority of the run time at an empty bed retention time (EBRT) of 60 s. The
      polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP)
      method was used to uncover the changes in the microbial community between the
      different layers. Analysis of SSCP profiles demonstrated significant differences
      in community structure from a layer to another with a strong decrease in species
      diversity towards the up layer. It was found that the used support was suitable
      for microorganism growth, and may have a potential application in H2S
      biofiltration system.

PMID- 21945210
TI  - Microbial fuel cell based biosensor for in situ monitoring of anaerobic digestion
      process.
AB  - A wall-jet microbial fuel cell (MFC) was developed for the monitoring of
      anaerobic digestion (AD). This biofilm based MFC biosensor had a character of
      being portable, short hydraulic retention time (HRT) for sample flow through and
      convenient for continuous operation. The MFC was installed in the recirculation
      loop of an upflow anaerobic fixed-bed (UAFB) reactor in bench-scale where pH of
      the fermentation broth and biogas flow were monitored in real time. External
      disturbances to the AD were added on purpose by changing feedstock concentration,
      as well as process configuration. MFC signals had good correlations with online
      measurements (i.e. pH, gas flow rate) and offline analysis (i.e. COD) over 6
      month operation. These results suggest that the MFC signal can reflect the
      dynamic variation of AD and can potentially be a valuable tool for monitoring and
      control of bioprocess.

PMID- 21945211
TI  - Chromatographic methods for the determination of therapeutic oligonucleotides.
AB  - Both DNA and RNA are being explored for their therapeutic potential against a
      wide range of diseases. As these new drugs emerge, new demands arise for the
      analysis and quantitation of these biomolecules. Pharmacokinetic and
      pharmacodynamic analysis requirements for drug approval place enormous challenges
      on the methods for analyzing these therapeutics. This review will focus on
      bioanalytical methods for DNA antisense and aptamers as well as small-interfering
      RNA (siRNA) therapeutics. Chromatography methods employing ultraviolet (UV),
      fluorescence and mass spectrometric (MS) detection along with matrix-assisted
      laser desorption/ionization (MALDI) will be covered. Sample preparation from
      biological matrices will be reviewed as well as metabolite analysis and
      identification. All of these techniques are important contributions toward
      oligonucleotide therapeutic development. They will also be important in microRNA
      (miRNA) biomarker discovery and RNomics in general, as more non-coding RNAs are
      inevitably discovered.

PMID- 21945212
TI  - Adaptation of the Carrez procedure for the purification of ferulic and p-coumaric
      acids released from lignocellulosic biomass prior to LC/MS analysis.
AB  - The objective of this study was to adapt and improve an environmentally friendly
      and fast routine method for the analysis of ferulic and p-coumaric acids released
      from grass cell-walls by alkaline hydrolysis. This methodological development was
      performed on maize samples selected for their contrasted contents in ferulic and
      p-coumaric acids as a consequence of their different maturity stages (from stage
      of 7th leaf with visible ligule to stage of silage harvest). We demonstrate that
      the Carrez method is an efficient substitute to the common solvent-consuming
      extraction by ethyl acetate for the preparation of samples suitable for HPLC-ESI
      MS analysis. We prove that it is possible to replace methanol by ethanol in the
      Carrez step and at last we propose a scale reduction of this procedure that offer
      a first step towards high throughput determinations. The new method leads to a
      solvent consumption reduced by a factor 100 and only requires ethanol as organic
      solvent.

PMID- 21945213
TI  - Discovery and evolving history of two genetically related but phenotypically
      different viruses, porcine circoviruses 1 and 2.
AB  - Porcine circoviruses (PCVs) belong to the genus Circovirus, family Circoviridae,
      and are the smallest non-enveloped, single stranded, negative sense, circular DNA
      viruses that replicate autonomously in mammalian cells. Two types of PCV have
      been characterised, PCV1 and PCV2 and these two viruses show 83% sequence
      identity at open reading frame (ORF) 1 and 67% identity at ORF2. PCV1 is a non
      pathogenic virus of pigs. In contrast, PCV2 has emerged as a major pathogen of
      swine around the world. The discovery of PCV1 and how the subsequent studies on
      this virus eventually led to the recognition and characterisation of PCV2, and
      the disease scenarios associated with PCV2, serve as a model of how
      multidisciplinary collaboration among field veterinarians, diagnosticians and
      researchers can lead to the rapid characterisation and control of a globally
      important emerging disease.

PMID- 21945215
TI  - Hantavirus pulmonary syndrome.
AB  - Hantavirus pulmonary syndrome (HPS) is a severe disease characterized by a rapid
      onset of pulmonary edema followed by respiratory failure and cardiogenic shock.
      The HPS associated viruses are members of the genus Hantavirus, family
      Bunyaviridae. Hantaviruses have a worldwide distribution and are broadly split
      into the New World hantaviruses, which includes those causing HPS, and the Old
      World hantaviruses [including the prototype Hantaan virus (HTNV)], which are
      associated with a different disease, hemorrhagic fever with renal syndrome
      (HFRS). Sin Nombre virus (SNV) and Andes virus (ANDV) are the most common causes
      of HPS in North and South America, respectively. Case fatality of HPS is
      approximately 40%. Pathogenic New World hantaviruses infect the lung
      microvascular endothelium without causing any virus induced cytopathic effect.
      However, virus infection results in microvascular leakage, which is the hallmark
      of HPS. This article briefly reviews the knowledge on HPS-associated hantaviruses
      accumulated since their discovery, less than 20 years ago.

PMID- 21945216
TI  - Analytic treatment of nuclear spin-lattice relaxation for diffusion in a cone
      model.
AB  - We consider nuclear spin-lattice relaxation rate resulted from a diffusion
      equation for rotational wobbling in a cone. We show that the widespread point of
      view that there are no analytical expressions for correlation functions for
      wobbling in a cone model is invalid and prove that nuclear spin-lattice
      relaxation in this model is exactly tractable and amenable to full analytical
      description. The mechanism of relaxation is assumed to be due to dipole-dipole
      interaction of nuclear spins and is treated within the framework of the standard
      Bloemberger, Purcell, Pound-Solomon scheme. We consider the general case of
      arbitrary orientation of the cone axis relative the magnetic field. The BPP
      Solomon scheme is shown to remain valid for systems with the distribution of the
      cone axes depending only on the tilt relative the magnetic field but otherwise
      being isotropic. We consider the case of random isotropic orientation of cone
      axes relative the magnetic field taking place in powders. Also we consider the
      cases of their predominant orientation along or opposite the magnetic field and
      that of their predominant orientation transverse to the magnetic field which may
      be relevant for, e.g., liquid crystals. Besides we treat in details the model
      case of the cone axis directed along the magnetic field. The latter provides
      direct comparison of the limiting case of our formulas with the textbook formulas
      for free isotropic rotational diffusion. The dependence of the spin-lattice
      relaxation rate on the cone half-width yields results similar to those predicted
      by the model-free approach.

PMID- 21945218
TI  - Expanding and enhancing our antibacterial arsenal.

PMID- 21945217
TI  - New aspects of RNA processing in prokaryotes.
AB  - The pivotal role of posttranscriptional gene regulation is strongly underlined by
      genome-wide analyses showing strikingly low correlation between mRNA and protein
      levels in bacterial and archaeal cells. The stability of an mRNA and its
      availability for translation contribute to posttranscriptional gene regulation,
      and are determined by the following factors: i) the cell-specific set of
      ribonucleases and related proteins, ii) regulatory RNAs, and iii) the sequence
      and structural features of the RNA molecule itself. High-resolution analyses of
      whole prokaryotic transcriptomes allow comprehensive mapping of processed
      transcripts, detection of essentially all expressed regulatory RNAs, and
      monitoring of the global impact of ribonucleases and other processing factors.
      This opens new perspectives for the understanding of the molecular mechanisms
      responsible for mRNA decay in prokaryotes.

PMID- 21945214
TI  - An unconventional pathway of mRNA cap formation by vesiculoviruses.
AB  - mRNAs of vesicular stomatitis virus (VSV), a prototype of nonsegmented negative
      strand (NNS) RNA viruses (e.g., rabies, measles, mumps, Ebola, and Borna disease
      viruses), possess the 5'-terminal cap structure identical to that of eukaryotic
      mRNAs, but the mechanism of mRNA cap formation is distinctly different from the
      latter. The elucidation of the unconventional capping of VSV mRNA remained
      elusive for three decades since the discovery of the cap structure in some viral
      and eukaryotic mRNAs in 1975. Only recently our biochemical studies revealed an
      unexpected strategy employed by vesiculoviruses (VSV and Chandipura virus, an
      emerging arbovirus) to generate the cap structure. This article summarizes the
      historical and current research that led to the discovery of the novel
      vesiculoviral mRNA capping reaction.

PMID- 21945219
TI  - Rapid and sensitive detection of mud crab Scylla serrata reovirus by a reverse
      transcription loop-mediated isothermal amplification assay.
AB  - Scylla serrata reovirus (SsRV) is one of the most prevalent viral pathogens of
      the mud crab (S. serrata). This pathogen is widespread in east China and causes
      severe economic losses to the nation's mud crab industry. Early detection of this
      pathogen is necessary for disease control and reduction of economic loss. In the
      present study, a reverse transcriptase loop-mediated isothermal amplification (RT
      LAMP) assay for the rapid and sensitive detection of SsRV was developed and
      evaluated. The LAMP reaction mix was optimized, as were the reaction temperature
      (62 degrees C) and the duration of the assay (60min). The sensitivity of the RT
      LAMP assay was determined to be 0.8fg SsRV dsRNA, which was 1000-fold higher than
      that of a one-step reverse transcription polymerase chain reaction (RT-PCR). The
      RT-LAMP assay also had higher sensitivity than a one-step RT-PCR, as it
      identified nine more positive cases from 55 mud crabs suspected of having SsRV.
      No cross-reactivity was found with the DNA/RNA of other tested viruses and SsRV
      negative animals. Importantly, the assay can be completed within 60min and is
      faster than conventional RT-PCR. In summary, the RT-LAMP assay is a simple, cost
      effective, sensitive, and specific tool for the rapid detection of SsRV
      infection.

PMID- 21945220
TI  - Inhibitory effects of silver nanoparticles on H1N1 influenza A virus in vitro.
AB  - Silver nanoparticles have demonstrated efficient inhibitory activities against
      human immunodeficiency virus (HIV) and hepatitis B virus (HBV). However, the
      effects of silver nanoparticles against H1N1 influenza A virus remain unexplored.
      In this study, the interaction of silver nanoparticles with H1N1 influenza A
      virus was investigated. Silver nanoparticles with mean particle diameters of 10nm
      were prepared for the hemagglutination inhibition test, the embryo inoculation
      assay, and the Mosmann-based 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) assay, where these tests were used to determine the inhibitory
      activity of silver nanoparticles on H1N1 influenza A virus. MDCK cells were used
      as the infection model. Electron microscopy analysis and flow cytometry assay
      were used to determine whether silver nanoparticles could reduce H1N1 influenza A
      virus-induced apoptosis in MDCK cells. This study demonstrates that silver
      nanoparticles have anti-H1N1 influenza A virus activities. The inhibitory effects
      of silver nanoparticles on influenza A virus may be a novel clinical strategy for
      the prevention of influenza virus infection during the early dissemination stage
      of the virus.

PMID- 21945221
TI  - Simultaneous detection of antibodies to five simian viruses in nonhuman primates
      using recombinant viral protein based multiplex microbead immunoassays.
AB  - Routine screening for infectious agents is critical in establishing and
      maintaining specific pathogen free (SPF) nonhuman primate (NHP) colonies. More
      efficient, higher throughput, less costly reagent, and reduced sample consumption
      multiplex microbead immunoassays (MMIAs) using purified viral lysates have been
      developed previously to address some disadvantages of the traditional individual
      enzyme-linked immunosorbent assay (ELISA) methods. To overcome some of the
      technical and biosafety difficulties in preparing antigens from live viruses for
      viral lysate protein based MMIAs, novel MMIAs using recombinant glycoprotein D
      precursor (gD) protein of herpesvirus B and four viral gag proteins of simian
      immunodeficiency virus (SIV), simian T Cell lymphotropic virus (STLV), simian
      foamy virus (SFV), and simian betaretrovirus (SRV) as antigens have been
      developed in the current study. The data showed that the recombinant viral
      protein based MMIAs detected simultaneously antibodies to each of these five
      viruses with high sensitivity and specificity, and correlated well with viral
      lysate based MMIAs. Therefore, recombinant viral protein based MMIA is an
      effective and efficient routine screening method to determine the infection
      status of nonhuman primates.

PMID- 21945222
TI  - Moderate mitral regurgitation accelerates left ventricular remodeling after
      posterolateral myocardial infarction.
AB  - BACKGROUND: Chronic ischemic mitral regurgitation (MR) is associated with poor
      outcome. However, the effect of chronic ischemic MR on left ventricular (LV)
      remodeling after posterolateral myocardial infarction (MI) remains controversial.
      We tested the hypothesis that moderate MR accelerates LV remodeling after
      posterolateral MI. METHODS: Posterolateral MI was created in 10 sheep. Cardiac
      magnetic resonance imaging was performed 2 weeks before and 2, 8, and 16 weeks
      after MI. Left ventricular and right ventricular volumes were measured, and
      regurgitant volume was calculated as the difference between LV and right
      ventricle stroke volumes. RESULTS: Multivariate mixed effects regression showed
      that LV volumes at end diastole and end systole and LV sphericity were strongly
      correlated with both regurgitant volume (p < 0.0001, p = 0.0086, and p = 0.0007,
      respectively) and percent infarct area (p = 0.0156, p = 0.0307, and p < 0.0001,
      respectively). Conversely, whereas LV hypertrophy (LV wall volume) increased from
      2 weeks to 16 weeks after MI, there was no effect of either regurgitant volume or
      percent infarct. CONCLUSIONS: Moderate MR accelerates LV remodeling after
      posterolateral MI. Further studies are needed to determine whether mitral valve
      repair is able to slow or reverse MI remodeling after posterolateral MI.

PMID- 21945223
TI  - Morbidity and mortality after esophagectomy following neoadjuvant chemoradiation.
AB  - BACKGROUND: Neoadjuvant chemoradiation (CRT) is an accepted treatment for locally
      advanced esophageal carcinoma. A survival benefit has not been definitively
      established, and there is concern that chemoradiation may increase postoperative
      morbidity and mortality. METHODS: A retrospective review was made of 138 patients
      treated for esophageal carcinoma between January 1999 and December 2009. Fifty
      four patients who underwent CRT followed by esophagectomy were compared with 84
      patients who underwent esophagectomy alone. RESULTS: The chemoradiation and
      esophagectomy alone cohorts were well matched on all preoperative variables.
      There was a higher percentage of Ivor Lewis procedures in the esophagectomy alone
      cohort (82.0%) compared with the CRT cohort (59.3%; p = 0.006). Thirty-five
      percent of the CRT group underwent transhiatal esophagectomy. Thirty-day
      mortality was 6.0% (5 of 84) in the esophagectomy alone cohort compared with 1.9%
      (1 of 54) in the CRT cohort (p = 0.5). Similarly, mean intensive care unit stay
      (4.7 versus 6.5 days; p = 0.5), ventilator time (2.4 versus 4.2 days; p = 0.5),
      and length of stay (13.5 versus 17 days; p = 0.2) did not differ significantly
      between the groups. The overall major complication rates were similar in the CRT
      and esophagectomy alone cohorts: 57.4% versus 56% (p = 0.98). Multivariate
      analysis determined that coronary artery disease (p = 0.01; odds ratio 3.5) and
      transthoracic esophagectomy (p = 0.05; odds ratio 1.4) were predictive of
      development of postoperative complications. Only cervical anastomotic location (p
      = 0.04; odds ratio 3.0) was predictive of anastomotic leak on multivariate
      analysis. CONCLUSIONS: Neoadjuvant chemoradiation does not appear to increase
      postoperative morbidity or mortality after esophagectomy. Major postoperative
      complications are associated with the transthoracic approach and preoperative
      coronary artery disease.

PMID- 21945224
TI  - Biomarkers of the insulin-like growth factor pathway predict progression and
      outcome in lung cancer.
AB  - BACKGROUND: Insulin-like growth factor 1 (IGF-I), IGF binding proteins (IGFBP) 1
      to 7, and C-peptide have been postulated to predict survival in non-small cell
      lung cancer (NSCLC). Studying serum levels in NSCLC patients treated with
      surgical resection may provide information on the aggressiveness of tumors and be
      predictive of disease recurrence. METHODS: Immunobead assays were used to measure
      pretreatment serum levels of IGF-I, IGFBP1 to IGFBP7, and C-peptide in 100 NSCLC
      patients. Of these, 59 had no metastatic progression (T1 to T4 N0 M0), whereas 41
      had positive lymph nodes (T1 to T4 N1 to N3 M0). Data were analyzed using the
      Mann-Whitney two-sided rank sum test or Kaplan-Meier curves. RESULTS: Low serum
      IGFBP5 levels correlated strongly with a positive nodal status (p < 0.001) and
      any incidence of disease recurrence (p = 0.003). Low serum levels of IGFBP5 also
      predicted poor recurrence-free survivals in the overall cohort (p <= 0.001) and
      in patients with no nodal metastases (p = 0.027). Conversely, a high serum level
      of IGFBP7 correlated with positive nodal status (p = 0.008), but was not
      prognostic for recurrence-free survival. No significant correlations were found
      for IGFBP5 or IGFBP7 for sex, age, race, smoking history, tumor histology, or
      fasting state. CONCLUSIONS: IGFBP5 and IGFBP7 had value as biomarkers for
      identifying NSCLC progression and patient outcome.

PMID- 21945225
TI  - Impact of hospital volume of thoracoscopic lobectomy on primary lung cancer
      outcomes.
AB  - BACKGROUND: This study evaluated hospital operative volume of video-assisted
      thoracoscopic surgery (VATS) lobectomy in primary lung cancer as a predictor of
      short-term outcomes after pulmonary lobectomy on a national scale. Some previous
      analyses comparing VATS vs open lobectomy outcomes have been limited by
      inaccuracies in patient cohort identification. METHODS: The 2008 Healthcare
      Utilization Project-Nationwide Inpatient Sample database was culled using the
      International Classification of Diseases (9th Clinical Modification) procedure
      codes specifically distinguishing VATS vs open lobectomies (32.41 and 32.49,
      respectively) available only after October 2007. High hospital VATS volume was
      defined as 95th percentile or higher (>20 VATS/year). Univariable and
      multivariable analyses were used to identify independent predictors of the
      following outcome measures: 30-day in-hospital morbidity and mortality, hospital
      length of stay (LOS), and hospital costs. RESULTS: We identified 6,292 primary
      lung cancer patients undergoing pulmonary lobectomy, including 1,523 undergoing
      VATS (24%). Compared with open, VATS patients had fewer complications (38% vs
      44%, p<0.001) and median LOS (5 vs 7 days; p<0.001). In multivariable analysis,
      VATS was an independent predictor of fewer total complications (odds ratio, 0.83;
      p=0.004) and shorter LOS (2.3+/-0.3-day difference, p<0.001). Patients undergoing
      VATS at high-volume VATS hospitals had shorter median LOS (4 vs 6 days, p=0.001)
      compared with low-volume VATS hospitals. Multivariable analysis showed high
      hospital VATS volume independently predicted shorter LOS (0.9+/-0.4-day
      difference, p=0.001). CONCLUSIONS: In a national database, VATS lobectomy was
      associated with fewer complications and shorter LOS than open lobectomy in
      primary lung cancer patients. Among patients undergoing VATS, high hospital
      volume was also associated with shorter LOS.

PMID- 21945226
TI  - Brief pressure overload preconditions rabbit myocardium independent of adenosine
      receptor activation.
AB  - BACKGROUND: We previously reported brief pressure overload of the left ventricle
      reduced myocardial infarct size. The role of adenosine receptors was investigated
      in this study. METHODS: Pressure overload was achieved by two 10-minute partial
      snaring of the ascending aorta. Systolic left ventricular pressure was raised 50%
      above baseline value. Ischemic preconditioning was elicited by two 10-minute
      coronary artery occlusions. Ten minutes after different pretreatments, 60-minute
      occlusion of the left anterior descending coronary artery followed by 3-hour
      reperfusion was done to induce infarction. The area at risk and myocardial
      infarct size were determined by Evans blue dye injection and triphenyltetrazolium
      chloride staining. RESULTS: Myocardial infarct size (mean +/- standard
      deviation), expressed as percentage of area at risk, was significantly reduced in
      the pressure overload group (19.3 +/- 2.5 %, p < 0.001) and in the ischemic
      preconditioning group (18.3 +/- 1.8 %, p < 0.001) versus the control group (27.3
      +/- 3.3 %). Pretreatment with 8-(p-sulfophenyl)-theophylline, an adenosine
      receptor antagonist, limited the protection by ischemic preconditioning (26.8 +/-
      3.7%), but not that by pressure overload (19.2 +/- 2.5%, p < 0.001). The 8-(p
      sulfophenyl)-theophylline did not significantly affect the extent of infarct
      (26.4 +/- 5.4%). The hemodynamics prior to treatment, area at risk, and mortality
      were not significantly different among all groups of animals. CONCLUSIONS: Brief
      pressure overload of the left ventricle preconditioned rabbit myocardium against
      infarction. Because 8-(p-sulfophenyl)-theophylline had no significant effect on
      this response, the results are consistent with the hypothesis that the underlying
      mechanism does not depend on activation of adenosine receptors.

PMID- 21945227
TI  - Aortic regurgitation after valve-sparing aortic root replacement: modes of
      failure.
AB  - BACKGROUND: Despite the positive clinical results of valve-sparing aortic root
      replacement, little is known about the causes of reoperations and the modes of
      failure. METHODS: From October 1999 to June 2010, 101 patients underwent valve
      sparing aortic root replacement using the David reimplantation technique. The
      definition of aortic root repair failure included the following: (1)
      intraoperative conversion to the Bentall procedure; (2) reoperation performed
      because of aortic regurgitation; and (3) aortic regurgitation equal to or greater
      than a moderate degree at the follow-up. Sixteen patients were considered to have
      repair failure. Three patients required intraoperative conversion to valve
      replacement, 3 required reoperation within 3 months, and another 8 required
      reoperation during postoperative follow-up. At initial surgery 5 patients had
      moderate to severe aortic regurgitation, 6 patients had acute aortic dissections,
      3 had Marfan syndrome, 2 had status post Ross operations, 3 had bicuspid aortic
      valves, and 1 had aortitis. Five patients had undergone cusp repair, including
      Arantius plication in 3 and plication at the commissure in 2. RESULTS: The causes
      of early failure in 6 patients included cusp perforation (3), cusp prolapse (3),
      and severe hemolysis (1). The causes of late failure in 10 patients included cusp
      prolapse (4), commissure dehiscence (3), torn cusp (2), and cusp retraction (1).
      Patients had valve replacements at a mean of 23 +/- 20.9 months after
      reimplantation and survived. CONCLUSIONS: Causes of early failure after valve
      sparing root replacement included technical failure, cusp lesions, and steep
      learning curve. Late failure was caused by aortic root wall degeneration due to
      gelatin-resorcin-formalin glue, cusp degeneration, or progression of cusp
      prolapse.

PMID- 21945228
TI  - An early experience using the technique of transoral OrVil EEA stapler for
      minimally invasive transthoracic esophagectomy.
AB  - BACKGROUND: Minimally invasive esophagectomy (MIE) has been performed using a
      variety of techniques evolving during the past decade. We present our initial
      experience and outcomes of patients undergoing transthoracic MIE using a circular
      end-to-side anastomosis created with the transorally directed EEA circular
      stapler OrVil (Covidien, New Haven, CT). Complications, including anastomotic
      leak and stricture occurrence, are reviewed. METHODS: A retrospective review
      evaluated consecutive patients undergoing MIE for esophageal cancer or related
      disease with intrathoracic end-to-side anastomoses using the transorally directed
      EEA circular stapler from December 2007 to May 2010. Medical records were
      reviewed for demographics, staging, neoadjuvant chemoradiotherapy, comorbidities,
      adjuvant therapy, complications, and survival. RESULTS: During this period, 51
      consecutive patients (84% male; mean age, 65 years) underwent MIE. Neoadjuvant
      chemoradiotherapy was performed in 32 patients, and 4 had intraoperative
      radiotherapy. Mean operative time was 338 minutes (range, 211 to 565 minutes),
      including the 4 patients with intraoperative radiotherapy. Operative time
      improved with experience (excluding intraoperative radiotherapy) from a mean of
      378 minutes (patients 1 to 14) to 300 minutes (patients 37 to 51). Median
      hospital stay was 11 days (range, 6 to 48 days). Anastomotic leaks occurred in 5
      patients (9.8%). Postoperative deaths included 1 in-hospital (2.0%) and 2 (3.9%)
      after discharge. Stricture was diagnosed and treated in 7 patients (13.7%).
      Follow-up was a median of 12 months (range, 1 to 31 months). CONCLUSIONS:
      Transthoracic MIE using an end-to-side anastomosis with the transorally directed
      EEA circular stapler resulted in acceptable stricture and leak rates with good
      outcomes comparable to published outcomes for open surgical resections.

PMID- 21945229
TI  - Self-made pericardial tube graft: a new surgical concept for treatment of graft
      infections after thoracic and abdominal aortic procedures.
AB  - BACKGROUND: The aim of this study was to evaluate a new surgical concept for the
      treatment of graft infections after operation or endovascular treatment of
      thoracic, thoracoabdominal, and abdominal aortic diseases. METHODS: Between 2004
      and 2011, 15 patients (mean age 72 +/- 10 years, 87% men) with prosthetic graft
      or endovascular graft infection were treated with complete removal of the
      infected prosthetic material, extensive debridement of the surrounding tissues,
      and orthotopic vascular reconstruction with self-made xenopericardial tube grafts
      constructed from a patch. Perioperative and long-term outcomes were evaluated.
      RESULTS: Perioperative mortality was 27% (n = 4). All deaths were due to
      multiorgan failure resulting from uncontrolled septicemia from the local
      infectious process. Mean observational follow-up was 24 months (5 to 83 months).
      Control computed tomographic scans showed normal findings at the operative site
      in all patients. Antibiotic treatment was continued for a mean of 6 months.
      Freedom from reinfection was 100%. Freedom from reoperation was also 100%.
      CONCLUSIONS: Treatment of graft infections after operation or endovascular
      treatment of thoracic, thoracoabdominal, and abdominal aortic diseases by
      complete removal of the infected prosthetic material and extensive debridement as
      well as orthotopic vascular reconstruction using self-made xenopericardial tube
      grafts as neoaortic segments provides excellent results with regard to durability
      and freedom from reinfection and reoperation. This new concept is an additional
      alternative to cryopreserved homografts that extends the armamentarium for
      treating patients with these highly complex conditions.

PMID- 21945231
TI  - Impaired long-term depression in schizophrenia: a cathodal tDCS pilot study.
AB  - BACKGROUND: Neural plasticity involves the reorganization of synaptic connections
      and represents the ability of the brain to adjust its function in response to
      challenge. Disturbed cortical plasticity has been linked to the pathophysiology
      of schizophrenia, with indirect evidence for disturbed plasticity in the disease
      state having been provided by postmortem studies and various animal models.
      However, glutamate-dependent long-term depression (LTD)-like cortical plasticity
      has not yet been investigated. OBJECTIVE: To investigate LTD-like cortical
      plasticity after transcranial direct current stimulation (tDCS) in schizophrenia
      patients. METHODS: Using excitability-diminishing cathodal tDCS, we performed the
      first in vivo assessment of glutamate-dependent LTD-like cortical plasticity in
      21 schizophrenia patients and 21 matched healthy control subjects. To reveal the
      physiologic basis of the hypothesized plasticity deficits, we tested different
      inhibitory and excitatory neuronal circuits with transcranial magnetic
      stimulation (TMS). RESULTS: Cathodal tDCS failed to reduce motor-evoked potential
      amplitudes in schizophrenia patients, indicating abolished LTD-like plasticity.
      Furthermore, schizophrenia patients had a prolonged GABA(B)-dependent cortical
      silent period (CSP) at baseline and tDCS failed to modulate the duration of CSP
      in the patient group. Finally, schizophrenia patients presented an elevated
      resting-motor threshold at baseline in comparison to healthy controls.
      CONCLUSIONS: The pattern of our results provides evidence for a specific
      plasticity deficit in schizophrenia patients, which might be associated with a
      hyperglutamatergic state. These findings may reflect a reduced signal-to-noise
      ratio and a disturbed filter function in schizophrenia patients. An increase of
      GABA(B)-activity may be a compensatory mechanism to dysfunctional LTD-like
      plasticity in schizophrenia.

PMID- 21945230
TI  - Human nasal olfactory epithelium as a dynamic marker for CNS therapy development.
AB  - Discovery of new central nervous system (CNS) acting therapeutics has been slowed
      down by the lack of useful applicable biomarkers of disease or drug action often
      due to inaccessibility of relevant human CNS tissue and cell types. In recent
      years, non-neuronal cells, such as astrocytes, have been reported to play a
      highly significant role in neurodegenerative diseases, CNS trauma, as well as
      psychiatric disease and have become a target for small molecule and biologic
      therapies. We report the development of a method for measuring pharmacodynamic
      changes induced by potential CNS therapeutics using nasal olfactory neural tissue
      biopsy. We validated this approach using a potential astrocyte-targeted
      therapeutic, thiamphenicol, in a pre-clinical rodent study as well as a phase 1
      human trial. In both settings, analysis of the olfactory epithelial tissue
      revealed biological activity of thiamphenicol at the drug target, the excitatory
      amino acid transporter 2 (EAAT2). Therefore, this biomarker approach may provide
      a reliable evaluation of CNS glial-directed therapies and hopefully improve
      throughput for nervous system drug discovery.

PMID- 21945232
TI  - MP's and VTE's: Fact or fiction.

PMID- 21945233
TI  - Preparedness of newly qualified midwives to deliver clinical care: an evaluation
      of pre-registration midwifery education through an analysis of key events.
AB  - OBJECTIVE: this study was part of a larger project commissioned to ascertain
      whether midwife teachers bring a unique contribution to the preparation of
      midwives for practice. The aim of this phase was to determine whether the student
      midwives' educational programme had equipped them to practise competently after
      entry to the professional register. DESIGN: this was a prospective, longitudinal
      qualitative study, using participant diaries to collect data. SETTING: data were
      collected from newly qualified midwives during the initial six months after they
      commenced their first post as a qualified midwife. PARTICIPANTS: the potential
      participants were all student midwives who were completing their education at one
      of six Universities (three in England, one in Scotland, one in Wales and one in
      Northern Ireland). Diary data were submitted by 35 newly qualified midwives; 28
      were graduates of the three year programme and seven of the shortened programme.
      MEASUREMENTS AND FINDINGS: diary entries were analysed using thematic analysis
      (Braun and Clarke, 2006), with a focus on identification of key events in the
      working lives of the newly qualified midwives. A total of 263 key events were
      identified, under three main themes: (1) impact of the event on confidence, (2)
      gaps in knowledge or experience and (3) articulated frustration, conflict or
      distress. KEY CONCLUSIONS: essentially, pre-registration education, delivered
      largely by midwife teachers and supported by clinical mentors, has been shown to
      equip newly qualified midwives to work effectively as autonomous practitioners
      caring for mothers and babies. While newly qualified midwives are able to cope
      with a range of challenging clinical situations in a safe manner, they lack
      confidence in key areas. Positive reinforcement by supportive colleagues plays a
      significant role in enabling them to develop as practitioners. IMPLICATIONS FOR
      PRACTICE: whilst acknowledging the importance of normality in childbearing there
      is a need within the curriculum to enable midwives to recognise and respond to
      complex care situations by providing theory, simulations and practice experience.

PMID- 21945234
TI  - Molecular and functional analysis of Drosophila single-minded larval central
      brain expression.
AB  - Developmental regulatory proteins are commonly utilized in multiple cell types
      throughout development. The Drosophila single-minded (sim) gene acts as master
      regulator of embryonic CNS midline cell development and transcription. However,
      it is also expressed in the brain during larval development. In this paper, we
      demonstrate that sim is expressed in three clusters of anterior central brain
      neurons: DAMv1/2, BAmas1/2, and TRdm and in three clusters of posterior central
      brain neurons: a subset of DPM neurons, and two previously unidentified clusters,
      which we term PLSC and PSC. In addition, sim is expressed in the lamina and
      medulla of the optic lobes. MARCM studies confirm that sim is expressed at high
      levels in neurons but is low or absent in neuroblasts (NBs) and ganglion mother
      cell (GMC) precursors. In the anterior brain, sim(+) neurons are detected in 1st
      and 2nd instar larvae but rapidly increase in number during the 3rd instar stage.
      To understand the regulation of sim brain transcription, 12 fragments
      encompassing 5'-flanking, intronic, and 3'-flanking regions were tested for the
      presence of enhancers that drive brain expression of a reporter gene. Three of
      these fragments drove expression in sim(+) brain cells, including all sim(+)
      neuronal clusters in the central brain and optic lobes. One fragment upstream of
      sim is autoregulatory and is expressed in all sim(+) brain cells. One intronic
      fragment drives expression in only the PSC and laminar neurons. Another
      downstream intronic fragment drives expression in all sim(+) brain neurons,
      except the PSC and lamina. Thus, together these two enhancers drive expression in
      all sim(+) brain neurons. Sequence analysis of existing sim mutant alleles
      identified three likely null alleles to utilize in MARCM experiments to examine
      sim brain function. Mutant clones of DAMv1/2 neurons revealed a consistent axonal
      fasciculation defect. Thus, unlike the embryonic roles of sim that control CNS
      midline neuron and glial formation and differentiation, postembryonic sim,
      instead, controls aspects of axon guidance in the brain. This resembles the roles
      of vertebrate sim that have an early role in neuronal migration and a later role
      in axonogenesis.

PMID- 21945236
TI  - The diagnosis of hypovolemia using advanced statistical methods.
AB  - AIM: Diagnosing hypovolemia is not a trivial task. Hypovolemia itself has several
      physical signs, but their specificity and sensitivity is limited, even using
      sophisticated monitoring techniques. However, diagnosing hypovolemia is crucial
      in critically ill patients to avoid worse outcomes. The aim of this paper is to
      provide methods for better estimation of the degree of hypovolemia in ill
      patients. METHODS: The so-called hypovolemic index (HVI) is introduced which
      classifies the degree of hypovolemia with a number in the interval [0, 1]. Four
      new methods are presented for the more precise diagnosis of hypovolemia. All
      methods rely on fuzzy logic. In the first method, clinical thresholds are used in
      the fuzzy rule system. The second method uses an iterative ROC analysis to
      determine the thresholds. The third one determines the thresholds using one
      single ROC analysis ("One step" method). The fourth method uses a genetic
      algorithm (GA) for the determination of the thresholds. The HVI is calculated
      using the data of patients from a previous investigation. Each method (except the
      first one) is tuned on a so called training database. Afterwards, they are
      carried out on a test database in order to determine the potential of the method.
      RESULTS: All four methods are capable of differentiating between hypovolemic and
      normovolemic patients. However, using the first and the second methods, several
      patients get a HVI of around 0.5, therefore, their degree of hypovolemia is
      ambiguous. The third and fourth methods deliver a better classification,
      hypovolemic and normovolemic patients are clearly separated from each other.
      CONCLUSION: All four novel methods deliver powerful tools for the diagnosis of
      hypovolemic patients. The degree of the hypovolemic state of each patient can be
      estimated with a hitherto unattained degree of reliability. Using ROC analysis
      and GA the estimation can be improved further.

PMID- 21945235
TI  - Nicotine self-administration and reinstatement of nicotine-seeking in male and
      female rats.
AB  - BACKGROUND: Tobacco addiction is a relapsing disorder that constitutes a
      substantial worldwide health problem, with evidence suggesting that nicotine and
      nicotine-associated stimuli play divergent roles in maintaining smoking behavior
      in men and women. While animal models of tobacco addiction that utilize nicotine
      self-administration have become more widely established, systematic examination
      of the multiple factors that instigate relapse to nicotine-seeking have been
      limited. Here, we examined nicotine self-administration and subsequent nicotine
      seeking in male and female Sprague-Dawley rats using an animal model of self
      administration and relapse. METHODS: Rats lever pressed for nicotine (0.03 and
      0.05 mg/kg/infusion, IV) during 15 daily 2-h sessions, followed by extinction of
      lever responding. Once responding was extinguished, we examined the ability of
      previously nicotine-paired cues (tone+light), the anxiogenic drug yohimbine
      (2.5mg/kg, IP), a priming injection of nicotine (0.3mg/kg, SC), or combinations
      of drug+cues to reinstate nicotine-seeking. RESULTS: Both males and females
      readily acquired nicotine self-administration and displayed comparable levels of
      responding and intake at both nicotine doses. Following extinction, exposure to
      the previously nicotine-paired cues or yohimbine, but not the nicotine-prime
      alone, reinstated nicotine-seeking in males and females. Moreover, when combined
      with nicotine-paired cues, both yohimbine and nicotine enhanced reinstatement. No
      significant sex differences or estrous cycle dependent changes were noted across
      reinstatement tests. CONCLUSIONS: These results demonstrate the ability to
      reinstate nicotine-seeking with multiple modalities and that exposure to nicotine
      associated cues during periods of a stressful state or nicotine can increase
      nicotine-seeking.

PMID- 21945238
TI  - Liberal bias mediates emotion recognition deficits in frontal traumatic brain
      injury.
AB  - It is well-known that patients having sustained frontal-lobe traumatic brain
      injury (TBI) are severely impaired on tests of emotion recognition. Indeed, these
      patients have significant difficulty recognizing facial expressions of emotion,
      and such deficits are often associated with decreased social functioning and poor
      quality of life. As of yet, no studies have examined the response patterns which
      underlie facial emotion recognition impairment in TBI and which may lend clarity
      to the interpretation of deficits. Therefore, the present study aimed to
      characterize response patterns in facial emotion recognition in 14 patients with
      frontal TBI compared to 22 matched control subjects, using a task which required
      participants to rate the intensity of each emotion (happiness, sadness, anger,
      disgust, surprise and fear) of a series of photographs of emotional and neutral
      faces. Results first confirmed the presence of facial emotion recognition
      impairment in TBI, and further revealed that patients displayed a liberal bias
      when rating facial expressions, leading them to associate intense ratings of
      incorrect emotional labels to sad, disgusted, surprised and fearful facial
      expressions. These findings are generally in line with prior studies which also
      report important facial affect recognition deficits in TBI patients, particularly
      for negative emotions.

PMID- 21945237
TI  - Agrimonia pilosa ethanol extract induces apoptotic cell death in HepG2 cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Agrimonia pilosa (AP) has been used as a
      traditional herbal medicine for treating various cancers and diseases in Asian
      countries. MATERIALS AND METHODS: Cell viability along with caspase-3/-7, caspase
      8 and caspase-9 activity were measured to detect apoptosis. The activity of the
      apoptotic factors bcl-2, bcl-xl, mcl-1, XIAP, BID, BIK, caspase-3, caspase-9 and
      PARP were measured by Western blotting. FACS analysis was used to analyze the
      cell cycle. RESULTS: APE inhibited the proliferation of HepG2 cells. Growth
      inhibition was associated with increased caspase activity and sub-G1 apoptotic
      fractions. When we measured the affect of APE on intracellular signaling, APE
      stimulated the apoptotic factors bcl-2, bcl-xl, mcl-1, XIAP, BID, BIK, caspase-3,
      caspase-9 and PARP in HepG2 cells. CONCLUSIONS: The results indicate that APE
      induces programmed cell death (apoptosis) in HepG2 cells and demonstrates one of
      the mechanisms underlying the therapeutic effects of the extract reported in
      previous studies.

PMID- 21945239
TI  - Unified scaling behavior of physical properties of clays in alcohol solutions.
AB  - This paper reports observation of universal scaling of physical properties of
      clay particles, Laponite (aspect ratio=30) (L) and Na Montmorillonite (MMT,
      aspect ratio=200), in aqueous alcohol solutions (methanol, ethanol and 1
      propanol) with solvent polarity, defined through reaction field factor
      f(OH)(E(0),n)=[(E(0) - 1/E(0) + 2) - (n(2) - 1/n(2) + 2)], at room temperature
      (20 degrees C). Here, E(0) and n are the static dielectric constant and
      refractive index of the solvent concerned. Physical properties (Z) such as zeta
      potential, effective aggregate size, viscosity and surface tension scaled with
      the relative solvent polarity as Z~deltaf(alpha); deltaf=(f(w)(E(0),n) -
      f(OH)(E(0),n)), where f(w)(E(0),n) is the reaction field factor for water, Z is
      the normalized physical property, and alpha is its characteristic scaling
      exponent. The value of this exponent was found to be invariant of aspect ratio of
      the clay but dependent on the solvent polarity only.

PMID- 21945240
TI  - Associated risk of XRCC1 and XPD cross talk and life style factors in progression
      of head and neck cancer in north Indian population.
AB  - Effective DNA repair machinery ensures maintenance of genomic integrity.
      Environmental insults, ageing and replication errors necessitate the need for
      proper DNA repair systems. Any alteration in DNA repair efficacy would play a
      dominant role in progression of squamous cell carcinoma of head and neck (SCCHN).
      Genotypes of XRCC1 gene-Arg194Trp, Arg280His, Arg399Gln and XPD Lys751Gln, by PCR
      RFLP were studied in 278 SCCHN patients and an equal number of matched healthy
      controls residing in north India. In XRCC1 polymorphisms, Arg194Trp and Arg399Gln
      variants showed a reduced risk, whereas, XPD Lys751Gln variants exhibited ~2-fold
      increase in SCCHN risk. With XRCC1-Arg280His variants, there was no association
      with SCCHN risk. Arg399Gln of XRCC1 appears to have a protective role in people
      those consume alcohol, while XPD Lys751Gln variants indicated ~2-fold increased
      risk of SCCHN in all the co-variate groups. Comparison of gene-gene interaction
      among XRCC1 Arg280His and XPD Lys751Gln suggested enhanced risk of SCCHN by ~2.3
      fold in group one and ~6.1-fold in group two. In dichotomized groups of this
      combination, the risk was ~2.4 times. Haplotype analysis revealed the frequency
      of C-G-G-G and C-A-G-G to be significantly associated with an increased risk of
      SCCHN. On the contrary, T-G-A-A significantly diminished the risk. CART analysis
      results showed that the terminal node that contains homozygous mutants of XPD
      Lys751Gln and XRCC1 Arg194Trp, wild type of XRCC1 Arg399Gln and homozygous mutant
      of XRCC1 Arg280His, represent the highest risk group. Our results demonstrate
      high degree of gene-gene interaction involving DNA repair genes of NER and BER
      pathways, namely XRCC1 and XPD. This study amply demonstrates positive
      association of XPD Arg751Gln polymorphism with an increased risk of SCCHN.
      Further, XRCC1 Arg280His variant though dormant individually, may also contribute
      to the development of cancer in combination with XPD Arg751Gln.

PMID- 21945242
TI  - Nuclear envelope defects impede a proper response to micronuclear DNA lesions.
AB  - When damage is inflicted in nuclear DNA, cells activate a hierarchical plethora
      of proteins that constitute the DNA damage response machinery. In contrast to the
      cell nucleus, the ability of micronuclear DNA lesions to activate this complex
      network is controversial. In order to determine whether the DNA contained in
      micronuclei is protected by the cellular damage response system, we studied the
      recruitment of excision repair factors to photolesions inflicted in the DNA of
      radiation-induced micronuclei. To perform this analysis, primary human dermal
      fibroblasts were exposed to UV-C light to induce photolesions in nuclear and
      micronuclear DNA. By means of immunofluorescence techniques, we observed that
      most micronuclei were devoid of NER factors. We conclude that UV photoproducts in
      micronuclei are mostly unable to generate an effective DNA damage response. We
      observed that the micronuclear envelope structure is a determinant factor that
      influences the repair of the DNA lesions inside micronuclei. Therefore, our
      results allow us to conclude that photolesions in radiation-induced micronuclei
      are poorly processed because the repair factors are unable to reach the
      micronuclear chromatin when a micronucleus is formed or after a genotoxic insult.

PMID- 21945241
TI  - Maintaining the end: roles of telomere proteins in end-protection, telomere
      replication and length regulation.
AB  - Chromosome end protection is essential to protect genome integrity. Telomeres,
      tracts of repetitive DNA sequence and associated proteins located at the
      chromosomal terminus, serve to safeguard the ends from degradation and unwanted
      double strand break repair. Due to the essential nature of telomeres in
      protecting the genome, a number of unique proteins have evolved to ensure that
      telomere length and structure are preserved. The inability to properly maintain
      telomeres can lead to diseases such as dyskeratosis congenita, pulmonary fibrosis
      and cancer. In this review, we will discuss the known functions of mammalian
      telomere-associated proteins, their role in telomere replication and length
      regulation and how these processes relate to genome instability and human
      disease.

PMID- 21945243
TI  - An unusual headache: sphenoiditis in children and adolescents.
AB  - Sphenoid sinus infection is a rare cause of headaches in children and
      adolescents. Its symptoms are often non-specific and confusing. The diagnosis is
      made on the history, examination, nasendoscopy, cultures and CT or MRI. Prompt
      and aggressive medical treatment in the form of parenteral antibiotics and nasal
      decongestants is advised to reduce the risk of serious complications such as
      permanent cranial neuropathies or intracranial spread. Surgical intervention is
      advocated when symptoms persist or complications develop. Although sphenoiditis
      is potentially devastating, early collaboration between pediatric medical and ENT
      surgical teams generally leads to an excellent outcome. This article presents
      three cases of adolescent sphenoid sinus infection, and reviews the literature on
      this uncommon condition.

PMID- 21945244
TI  - Acute mastoiditis in children in Sweden 1993-2007--no increase after new
      guidelines.
AB  - OBJECTIVE: To study whether the incidence and characteristics of acute
      mastoiditis in children changed in Sweden following the introduction of new
      guidelines for diagnosis and treatment of acute otitis media advocating "watchful
      waiting" as an option in children 2-16 years of age with uncomplicated acute
      otitis media. METHODS: The records for all patients treated for mastoiditis
      during 1993-2007 at all Ear, Nose and Throat departments in Sweden were reviewed
      retrospectively according to defined criteria for acute mastoiditis. In this
      study the data from children aged 0-16 years were analyzed and compared 71/2
      years before and 71/2 years after the introduction of the new guidelines in 2000.
      RESULTS: A total of 577 cases aged 0-16 years fulfilled the inclusion criteria
      during the whole study period. Cases involving cholesteatoma were excluded. The
      number of children affected by acute mastoiditis did not increase after the
      introduction of new guidelines. Acute mastoiditis was most common in children
      younger than two years of age. The proportion of acute mastoiditis increased
      after 2000 in the group aged 2-23 months although they were not affected
      concerning treatment by the new guidelines. No decrease was found in the
      frequency of prehospital antibiotic treatment among the children admitted with
      acute mastoiditis, and no increase was seen in the duration of ear symptoms
      before hospital admission, duration of hospital stay, or in the frequency of
      complications or mastoidectomies, after the introduction of the new guidelines in
      either group of children. CONCLUSIONS: The incidence of acute mastoiditis in
      children in Sweden did not increase following the introduction of new guidelines
      in 2000 for the diagnosis and treatment of acute otitis media. This is despite
      the fact that a significant decrease in antibiotic prescriptions for otitis media
      has been reported during the same time period. The characteristics of acute
      mastoiditis reflecting severity of illness did not change over time. Acute
      mastoiditis was most common and increased after 2000 only in children younger
      than two years of age in which antibiotics were still recommended in all cases of
      acute otitis media.

PMID- 21945245
TI  - [Guillain-Barre syndrome: clinical presentation and prognosis in children under
      six years-old].
AB  - INTRODUCTION: Guillain-Barre syndrome (GBS) is an acute polyneuropathy that is
      difficult to diagnose in young children. OBJECTIVES: To review the form of
      presentation of GBS in children under six years-old at the time of onset and the
      symptoms they had until the diagnosis, the findings in the complementary tests,
      and the progression and prognosis. PATIENTS AND METHODS: All patients less than 6
      years-old who fulfilled the Asbury et al criteria for the diagnosis of GBS were
      reviewed. RESULTS: Eight patients with a mean age of 3.4 years were included. Of
      those 75% recorded a previous infection. The symptoms prior to the diagnosis were
      very heterogeneous which entailed a wide differential diagnosis with many
      complementary examinations. The mean time to diagnosis was 8.5 days. All of them
      (100%) had motor involvement in the lower limbs, 75% in the upper limbs and 12%
      in the respiratory muscles. Sensory and cranial nerve involvement was observed in
      62.5% and 25%, respectively. Admission to intensive care was required for 25% of
      the patients. Albumino-cytological dissociation was observed in the CSF in 83.3%
      and all the electrophysiological tests were positive with different patterns. The
      prognosis was excellent in all patients. CONCLUSIONS: GBS in children under 6
      years-old is difficult to diagnosis due to the signs of onset often being
      unspecific. This entails a wide differential diagnosis, with the subsequent
      diagnostic delay. There is a good prognosis in all the electrophysiological sub
      types in this age group.

PMID- 21945246
TI  - [Measles pneumonia].

PMID- 21945247
TI  - Novel insights into the distribution of cardiac HCN channels: an expression study
      in the mouse heart.
AB  - HCN pacemaker channels (I(f) channels) are believed to contribute to important
      functions in the heart; thus these channels became an attractive target for
      generating transgenic mouse mutants to elucidate their role in physiological and
      pathophysiological cardiac conditions. A full understanding of cardiac I(f) and
      the interpretation of studies using HCN mouse mutants require detailed
      information about the expression profile of the individual HCN subunits. Here we
      investigate the cardiac expression pattern of the HCN isoforms at the mRNA as
      well as at the protein level. The specificity of antibodies used was strictly
      confirmed by the use of HCN1, HCN2 and HCN4 knockout animals. We find a low, but
      highly differential HCN expression profile outside the cardiac conduction pathway
      including left and right atria and ventricles. Additionally HCN distribution was
      investigated in tissue slices of the sinoatrial node, the atrioventricular node,
      the bundle of His and the bundle branches. The conduction system was marked by
      acetylcholine esterase staining. HCN4 was confirmed as the predominant isoform of
      the primary pacemaker followed by a distinct expression of HCN1. In contrast HCN2
      shows only a confined expression to individual pacemaker cells. Immunolabeling of
      the AV-node reveals also a pronounced specificity for HCN1 and HCN4. Compared to
      the SN and AVN we found a low but selective expression of HCN4 as the only
      isoform in the atrioventricular bundle. However in the bundle branches HCN1, HCN4
      and also HCN2 show a prominent and selective expression pattern. Our results
      display a characteristic distribution of individual HCN isoforms in several
      cardiac compartments and reveal that beside HCN4, HCN1 represents the isoform
      which is selectively expressed in most parts of the conduction system suggesting
      a substantial contribution of HCN1 to pacemaking.

PMID- 21945248
TI  - Camelpox virus.
AB  - Camelpox virus (CMLV) causes a smallpox-like illness in a unique host, the camel.
      The disease is enzootic in almost all regions where camel husbandry is practiced,
      and is responsible for severe economic losses. Although it is genetically the
      closest known virus to variola virus, the etiologic agent of smallpox, CMLV
      remains poorly studied. It is characterized by a narrow host range, the capacity
      to induce giant cells in culture and to counteract host immune defenses; however,
      the genetic bases associated with these features are not understood. Also, it
      still needs to be demonstrated whether CMLV strains of variable virulence
      circulate and how arthropod vectors might be involved in virus transmission.
      Current evidence indicates that, under certain circumstances, CMLV can be mildly
      pathogenic in humans. A reservoir host other than camels is unlikely to exist. We
      review here current knowledge of CMLV, including clinical and laboratory aspects
      of the disease. We also discuss prevention and therapy by use of vaccines and
      antiviral treatments, as well as the possibility of camelpox eradication.

PMID- 21945249
TI  - Virological failure of intralesional cidofovir therapy in recurrent respiratory
      papillomatosis is not associated with genetic or epigenetic changes of HPV11:
      complete genome comparison of sequential isolates.
AB  - Five sequential human papillomavirus type 11 (HPV11) positive samples collected
      from an aggressive juvenile onset recurrent respiratory papillomatosis before,
      during and after intralesional cidofovir therapy leading to virological failure
      after initial response were analyzed. Sequencing of the complete genome as well
      as methylation analysis by bisulfate modification and sequencing of the long
      control region (LCR) were performed to seek for genetic and epigenetic changes as
      a possible background for therapy failure. Single-strand conformation
      polymorphism of E1, E2, E6, E7 and LCR was used to exclude the presence of
      multiple HPV11 infection. All five complete genomes were identical and all four
      E2 binding sites in the LCR were uniformly unmethylated in all five genomes. Thus
      the virological failure was not due to virological factors suggesting that
      cidofovir action may depend more heavily on the host.

PMID- 21945250
TI  - Synthesis and biological evaluation of novel 2-arylamino-3
      (arylsulfonyl)quinoxalines as PI3Kalpha inhibitors.
AB  - A series of novel 2-arylamino-3-(arylsulfonyl)quinoxalines was synthesized
      through a newly developed approach. All synthesized target compounds were
      screened for their cytotoxicities against cancer cell lines including PC3, A549,
      HCT116, HL60 and KB. Representative compounds with favorable cytotoxicities were
      tested for their PI3Kalpha inhibitory activities. Among the synthesized target
      compounds, 17 (PI3Kalpha IC(50): 0.07 MUM) displayed the most potent cellular
      activities (IC(50) values of 0.14 MUM, 0.07 MUM, 0.95 MUM and 0.05 MUM against
      PC3, A549, HCT116 and HL 60, respectively).

PMID- 21945251
TI  - Discovery of a new class of bicyclic substituted hydroxyphenylmethanones as
      17beta-hydroxysteroid dehydrogenase type 2 (17beta-HSD2) inhibitors for the
      treatment of osteoporosis.
AB  - E2 deficiency in elderly people has directly an effect on the skeleton and can
      lead to osteoporosis. As 17beta-hydroxysteroid dehydrogenase type 2 (17beta-HSD2)
      catalyses the conversion between active 17beta-hydroxysteroid estradiol (E2) and
      testosterone (T) into their less active 17-ketosteroid and has been found in
      bones, 17beta-HSD2 inhibitor may provide a new approach in the onset of
      osteoporosis. Bicyclic substituted hydroxyphenylmethanone derivatives were
      synthesised as steroidomimetics of the substrate E2 and were evaluated for their
      17beta-HSD2 inhibition and their selectivity toward 17beta-HSD1, catalysing the
      reverse reaction the conversion of estrone (E1) into E2. Highly selective
      compounds (11, 12, 14, 21 and 22) have been identified, the most promising one
      (12) showing an IC(50) value in the low nanomolar range (101 nM) and a
      selectivity factor of 13 toward 17beta-HSD1. These results make compound 12 an
      interesting candidate for further biological evaluation.

PMID- 21945252
TI  - Distinct immunoregulatory properties of macrophage migration inhibitory factors
      encoded by Eimeria parasites and their chicken host.
AB  - Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that
      plays an important role in host defense against a variety of microorganisms
      including protozoan parasites. Interestingly, some microbial pathogens also
      express a MIF-like protein, although its role in disease pathogenesis is not well
      understood. The aim of this study was to compare an Eimeria-encoded MIF (E.MIF)
      protein with chicken MIF (C.MIF) on the basis of their structural, immunological,
      and biological properties. E.MIF and C.MIF proteins, each with a glutathione S
      transferase epitope tag, were expressed in Escherichia coli or COS-7 cells and
      purified by glutathione affinity chromatography. Rabbit antisera against the
      purified proteins demonstrated their mutual immunological cross-reactivity on
      Western blots, and immunolocalized intracellular native E.MIF to the Eimeria
      schizont, merozoite, and oocyst life cycle stages. HD11 chicken macrophages
      treated in vitro with C.MIF recombinant protein expressed increased levels of
      transcripts encoding interleukin-6 (IL-6), IL-17, and tumor necrosis factor
      superfamily member 15 (TNFSF15), but decreased levels of IL-8 transcripts,
      compared with cells treated with the PBS control; similar treatment with E.MIF
      only down-regulated IL-8 transcripts. Unlike recombinant E.MIF, C.MIF exhibited
      in vitro chemotactic activity for HD11 cells. Conversely, E.MIF, but not C.MIF,
      enhanced protection against experimental Eimeria infection, compared with the PBS
      control. These studies provide evidence for overlapping structural and antigenic
      properties, but distinct immunoregulatory roles, of E.MIF and C.MIF.

PMID- 21945253
TI  - Preparation and immunological effectiveness of a swine influenza DNA vaccine
      encapsulated in chitosan nanoparticles.
AB  - Preparation conditions of a DNA vaccine against swine influenza encapsulated in
      chitosan nanoparticles were determined. The nanoparticles were prepared according
      to a complex coacervation method using chitosan as a biodegradable matrix forming
      polymer. Under the preparation conditions, chitosan nanoparticles containing the
      DNA vaccine were produced with good morphology, high encapsulation rate and high
      stability. Transfection test indicated that the vaccine could be expressed as an
      antigen in cells, and maintained good bioactivity. In addition, better immune
      responses of mice immunized with the chitosan nanoparticles containing the DNA
      vaccine were induced and prolonged release of the plasmid DNA was achieved
      compared to the DNA vaccine alone. These results laid a foundation for further
      development of DNA vaccines in nanoparticles before ultimate industrial
      application.

PMID- 21945254
TI  - Preparing for the next public debate: universal vaccination against hepatitis B.
AB  - WHO have long called for universal vaccination against hepatitis B worldwide.
      However, in north-western Europe low incidence of the disease has fueled debate
      whether targeted or universal vaccination strategies are the way to go for.
      Careful assessment has made it clear that the extensive targeted hepatitis B
      vaccination programmes in the Netherlands nevertheless fail to reach a
      significant part of the risk groups and have not succeeded in eliminating the
      disease. Modelling suggests that the public health benefits obtained through
      targeted programmes could be augmented considerably by universal vaccination.
      Therefore, the Minister of Health of the Netherlands has decided to implement
      universal vaccination by October 2011. We illustrate the case of the Netherlands
      and explore lessons, which can be learnt from the vaccination programmes against
      HPV and influenza A/H1N1 and how to prepare for a potential public debate that
      might arise when implementing universal vaccination against hepatitis B.

PMID- 21945255
TI  - Improved immune responses in mice using the novel chitosan adjuvant ViscoGel,
      with a Haemophilus influenzae type b glycoconjugate vaccine.
AB  - An immune response to an antigen is more efficiently induced in combination with
      an adjuvant. Chitosan has due to documented immunostimulatory characteristics
      been proposed as an adjuvant candidate. However, a disadvantage with chitosan is
      its poor solubility at physiological pH. We have circumvented this obstacle by
      using a soluble type of chitosan (Viscosan), with a degree of deacetylation (DD)
      of 50% and a random distribution of acetyl groups. A hydrogel, ViscoGel, was made
      from Viscosan which was further mechanically processed into gel particles of
      predefined size. The first cells to infiltrate ViscoGel in mice, were identified
      mainly as neutrophils, detected already after 4 h. ViscoGel's impact on the
      immune response in mice together with a commercial vaccine against Haemophilus
      influenzae type b (Act-HIB) was then studied. Mixing Act-HIB with ViscoGel,
      induced significantly enhanced IgG1 and IgG2a titers in serum (p<0.05). We could
      reduce the antigen dose ten-fold in combination with ViscoGel and still obtain
      antibody titers similar to 2 MUg Act-HIB administered alone. In addition, the Act
      HIB specific cellular response was stronger in mice vaccinated together with
      ViscoGel (p<0.05). The cytokine response after vaccination with Act-Hib together
      with ViscoGel was of a mixed type. We found elevated levels of the Th1 associated
      cytokine INF-gamma, the Th2-cytokine IL-4, the proinflammatory IL-6 and IL-17A,
      and the regulatory cytokine IL-10. Similar effects were seen when the adjuvant
      was administered either subcutaneously or intramuscularly. Taken together, using
      vaccination against H. influenzae type b as a model, we here show proof of
      concept for the novel vaccine adjuvant candidate, ViscoGel.

PMID- 21945256
TI  - Vaccine effectiveness for laboratory-confirmed influenza in children 6-59 months
      of age, 2005-2007.
AB  - To estimate the effectiveness of influenza vaccine against medical care visits
      for laboratory-confirmed influenza in young children we conducted a matched case
      control study in children with acute respiratory illness or fever from 2005-2007.
      Influenza vaccine effectiveness (VE) was calculated using cases with laboratory
      confirmed influenza and controls who tested negative for influenza. The
      effectiveness of influenza vaccine in fully vaccinated children 6-59 months of
      age was 56% (95% CI: 25%-74%); a significant VE was not found for partial
      vaccination.

PMID- 21945257
TI  - Multiple amino acid changes at the first glycosylation motif in NS1 protein of
      West Nile virus are necessary for complete attenuation for mouse
      neuroinvasiveness.
AB  - West Nile virus (WNV), like all members of the Japanese encephalitis (JE)
      serogroup except JE virus, contains three N-linked glycosylation (N-X-S/T) sites
      in the NS1 protein at asparagine residues NS1(130), NS1(175) and NS1(207).
      Previously we showed that the ablation of these glycosylation sites in WNV, by
      substitution of asparagine for alanine, attenuated mouse neuroinvasiveness;
      however, full attenuation was not achieved and the virus retained a
      neurovirulence phenotype. Sequence of viral RNA extracted from mouse brains
      revealed a reversion at the NS1(130) site in some mice that succumbed to the
      attenuated NS1(130A/175A/207A) strain. Here, we further attenuated WNV by
      mutating the asparagine to serine or glutamine in addition to mutating other
      residues in the NS1(130-132) glycosylation motif. These mutants proved to further
      attenuate WNV for both neuroinvasiveness and neurovirulence in mice. NS1(130
      132QQA/175A/207A), the most attenuated mutant virus, showed modest changes in
      infectivity titers versus the parental strain, was not temperature sensitive, and
      did not show reversion in mice. Mutant virus was completely attenuated for
      neuroinvasiveness after intraperitoneal inoculation with >1,000,000 PFU, and mice
      were protected against lethal challenge. Overall, we showed that changing the
      asparagine of the NS1(130) glycosylation motif to a serine or glutamine
      attenuated WNV further than the asparagine to alanine substitution. Further,
      mutating all three of the amino acids of the NS1(130-132) glycosylation motif
      (NTT-QQA) along with NS1(175) and NS1(207) asparagine to alanine mutations gave
      the most stable and attenuated strain.

PMID- 21945258
TI  - A phase I randomized, double-blind, controlled trial of 2009 influenza A (H1N1)
      inactivated monovalent vaccines with different adjuvant systems.
AB  - METHODS: We conducted a phase I, multicenter, randomized, double-blind, placebo
      controlled, multi-arm (10) parallel study involving healthy adults to evaluate
      the safety and immunogenicity of influenza A (H1N1) 2009 non-adjuvanted and
      adjuvanted candidate vaccines. Subjects received two intramuscular injections of
      one of the candidate vaccines administered 21 days apart. Antibody responses were
      measured by means of hemagglutination-inhibition assay before and 21 days after
      each vaccination. The three co-primary immunogenicity end points were the
      proportion of seroprotection >70%, seroconversion >40%, and the factor increase
      in the geometric mean titer >2.5. RESULTS: A total of 266 participants were
      enrolled into the study. No deaths or serious adverse events were reported. The
      most commonly solicited local and systemic adverse events were injection-site
      pain and headache, respectively. Only three subjects (1.1%) reported severe
      injection-site pain. Four 2009 influenza A (H1N1) inactivated monovalent
      candidate vaccines that met the three requirements to evaluate influenza
      protection, after a single dose, were identified: 15 MUg of hemagglutinin antigen
      without adjuvant; 7.5 MUg of hemagglutinin antigen with aluminum hydroxide, MPL
      and squalene; 3.75 MUg of hemagglutinin antigen with aluminum hydroxide and MPL;
      and 3.75 MUg of hemagglutinin antigen with aluminum hydroxide and squalene.
      CONCLUSIONS: Adjuvant systems can be safely used in influenza vaccines, including
      the adjuvant monophosphoryl lipid A (MPL) derived from Bordetella pertussis with
      squalene and aluminum hydroxide, MPL with aluminum hydroxide, and squalene and
      aluminum hydroxide.

PMID- 21945259
TI  - Construction and immunogenicity of recombinant adenovirus expressing ORF2 of PCV2
      and porcine IFN gamma.
AB  - The capsid structural protein encoded by the gene ORF2 of Porcine Circovirus Type
      2 is critical for eliciting the broad protective immunity. We constructed and
      characterized the recombinant adenovirus encoding the capsid and porcine IFN
      gamma, designated as rAd-ORF2-IFN-gamma. The construct was further confirmed by
      the enzyme digestion, PCR, sequencing and transfection. The humoural immunity to
      the capsid protein, induced by the recombinant in the mice, was tested by ELISA.
      Notably, this recombinant induced a much better ORF2-specific antibody response
      than that of rAd-ORF2 alone or the adenovirus itself. Clearly, the porcine IFN
      gamma could strongly enhance the immunogenicity of ORF2. The results showed that
      the recombinant adenovirus might be an attractive candidate vaccine for
      preventing the disease associated with PCV2 infection.

PMID- 21945260
TI  - Enhanced immune sera and vaccine: safe approach to treat scorpion envenoming.
AB  - Irradiation of Androctonus australis hector venom using a dose of 2 kGy has
      successfully abolished toxicity without reducing its antigenic or immunogenic
      properties. Toxicity of irradiated antigen was abolished until 20 times of LD(50)
      of native venom. Analysis of physiopathological effects induced by native and
      irradiated venoms was assessed by the analysis of tissue damage,
      immunohistochemistry and metabolical analysis in the organs (heart, lungs and
      liver). Immunological response of Aah venom using native or irradiated venom
      showed high titers of IgG1 in the plasma of immunized animals with native venom
      suggesting that Th2 cells were predominantly involved in the immune response. In
      the other hand, irradiated venom induced high titers of IgG2, indicating a
      predominantly Th1 type response. A protective effect of immunized mice with
      irradiated venom was evaluated. Immunized mice were protected from the toxic
      effects of native venom doses at one, three and six months after immunization.
      Mice were protected against a challenge of 4 LD(50) doses of native venom, one
      month after immunization. This protective effect was improved and effective at 3
      and 6 months, all immunized mice were protected respectively against 6 and 10
      LD(50) of native venom. At the one-month time point, the protective effect of
      mice was associated with high levels of antibodies in the plasma of immunized
      mice. However, despite the persistence of higher protection levels, the antibody
      titers decreased in a time-dependent manner. These results suggest that
      additional factors other than circulating antibodies provided the long-term
      protective activity produced by immunization with irradiated venom.

PMID- 21945261
TI  - Borrelia burgdorferi BBA52 is a potential target for transmission blocking Lyme
      disease vaccine.
AB  - The surface-exposed antigens of Borrelia burgdorferi represent important targets
      for induction of protective host immune responses. BBA52 is preferentially
      expressed by B. burgdorferi in the feeding tick, and a targeted deletion of bba52
      interferes with vector-host transitions in vivo. In this study, we demonstrate
      that BBA52 is an outer membrane surface-exposed protein and that disulfide
      bridges take part in the homo-oligomeric assembly of native protein. BBA52
      antibodies lack detectable borreliacidal activities in vitro. However, active
      immunization studies demonstrated that BBA52 vaccinated mice were significantly
      less susceptible to subsequent tick-borne challenge infection. Similarly, passive
      transfer of BBA52 antibodies in ticks completely blocked B. burgdorferi
      transmission from feeding ticks to naive mice. Taken together, these studies
      highlight the role of BBA52 in spirochete dissemination from ticks to mice and
      demonstrate the potential of BBA52 antibody-mediated strategy to complement the
      ongoing efforts to develop vaccines for blocking the transmission of B.
      burgdorferi.

PMID- 21945262
TI  - Safety and immunogenicity of long HSV-2 peptides complexed with rhHsc70 in HSV-2
      seropositive persons.
AB  - HSV-2, the primary causative agent of genital herpes, establishes latency in
      sensory ganglia and reactivates causing recurrent lesions and viral shedding.
      Induction or expansion of CD4(+) and CD8(+) T cell responses are expected to be
      important for a successful therapeutic vaccine against HSV-2. A candidate vaccine
      consisting of 32 synthetic 35mer HSV-2 peptides non-covalently complexed with
      recombinant human Hsc70 protein (named HerpV, formerly AG-707) was tested for
      safety and immunogenicity in a Phase I study. These peptides are derived from 22
      HSV-2 proteins representative of all phases of viral replication. Thirty-five HSV
      2 infected participants were randomized and treated in one of four groups:
      HerpV+QS-21 (saponin adjuvant), HerpV, QS-21, or vehicle. The vaccine was well
      tolerated and safe. All seven participants with evaluable samples who were
      administered HerpV with QS-21 demonstrated a statistically significant CD4(+) T
      cell response to HSV-2 antigens, and the majority of such participants
      demonstrated a statistically significant CD8(+) T cell response as well. To our
      knowledge, this is the first candidate vaccine against HSV-2 to demonstrate a
      broad CD4(+) and CD8(+) T cell response in HSV-2(+) participants, and the first
      HSP-based vaccine to show immune responses against viral antigens in humans.

PMID- 21945264
TI  - Economic evaluation of second generation pneumococcal conjugate vaccines in
      Norway.
AB  - BACKGROUND: A seven valent pneumococcal conjugate vaccine (PCV7) was introduced
      in the Norwegian childhood immunization programme in 2006, and since then the
      incidence of invasive pneumococcal disease has declined substantially. Recently,
      two new second generation pneumococcal conjugate vaccines have become available,
      and an update of the economic evidence is needed. The aim of this study was to
      estimate incremental costs, health effects and cost-effectiveness of the
      pneumococcal conjugate vaccines PCV7, PCV13 and PHiD-CV in Norway. METHODS: We
      used a Markov model to estimate costs and epidemiological burden of pneumococcal-
      and NTHi-related diseases (invasive pneumococcal disease (IPD), Community
      Acquired Pneumonia (CAP) and acute otitis media (AOM)) for a specific birth
      cohort. Using the most relevant evidence and assumptions for a Norwegian setting,
      we calculated incremental costs, health effects and cost-effectiveness for
      different vaccination strategies. In addition we performed sensitivity analyses
      for key parameters, tested key assumptions in scenario analyses and explored
      overall model uncertainty using probabilistic sensitivity analysis. RESULTS: The
      model predicts that both PCV13 and PHiD-CV provide more health gains at a lower
      cost than PCV7. Differences in health gains between the two second generation
      vaccines are small for invasive pneumococcal disease but larger for acute otitis
      media and myringotomy procedures. Consequently, PHiD-CV saves more disease
      treatment costs and indirect costs than PCV13. CONCLUSION: This study predicts
      that, compared to PVC13, PHiD-CV entails lower costs and greater benefits if the
      latter is measured in terms of quality adjusted life years. PVC13 entails more
      life years gained than PHiD-CV, but those come at a cost of NOK 3.1 million
      (~?0.4 million) per life year. The results indicate that PHiD-CV is cost
      effective compared to PCV13 in the Norwegian setting.

PMID- 21945263
TI  - Inflammatory responses to trivalent influenza virus vaccine among pregnant women.
AB  - OBJECTIVE: In the U.S., seasonal trivalent influenza virus vaccine (TIV) is
      currently universally recommended for all pregnant women. However, data on the
      maternal inflammatory response to vaccination is lacking and would better
      delineate the safety and clinical utility of immunization. In addition, for
      research purposes, vaccination has been used as a mild immune trigger to examine
      in vivo inflammatory responses in nonpregnant adults. The utility of such a model
      in pregnancy is unknown. Given the clinical and empirical justifications, the
      current study examined the magnitude, time course, and variance in inflammatory
      responses following seasonal influenza virus vaccination among pregnant women.
      METHODS: Women were assessed prior to and at one day (n=15), two days (n=10), or
      approximately one week (n=21) following TIV. Serum interleukin (IL)-6, tumor
      necrosis factor (TNF)-alpha, C-reactive protein (CRP), and macrophage migration
      inhibitory factor (MIF) were determined by high sensitivity immunoassay. RESULTS:
      Significant increases in CRP were seen at one and two days post-vaccination
      (ps<05). A similar effect was seen for TNF-alpha, for which an increase at two
      days post-vaccination approached statistical significance (p=.06). There was
      considerable variability in magnitude of response; coefficients of variation for
      change at two days post-vaccination ranged from 122% to 728%, with the greatest
      variability in IL-6 responses at this timepoint. CONCLUSIONS: Trivalent influenza
      virus vaccination elicits a measurable inflammatory response among pregnant
      women. There is sufficient variability in response for testing associations with
      clinical outcomes. As adverse perinatal health outcomes including preeclampsia
      and preterm birth have an inflammatory component, a tendency toward greater
      inflammatory responding to immune triggers may predict risk of adverse outcomes,
      providing insight into biological mechanisms underlying risk. The inflammatory
      response elicited by vaccination is substantially milder and more transient than
      seen in infectious illness, arguing for the clinical value of vaccination.
      However, further research is needed to confirm that the mild inflammatory
      response elicited by vaccination is benign in pregnancy.

PMID- 21945265
TI  - Considerations for clinics and practitioners treating foreign patients with
      assisted reproductive technology: lessons from experiences at Ghent University
      Hospital, Belgium.
AB  - Cross-border reproductive care (CBRC) is not a new concept, having been around
      since the beginning of assisted reproductive technology. Countries having taken
      the lead in developing new technologies have seen an influx of patients from
      other countries, because of legal limitations or the unavailability of good
      quality care in their home country. This paper describes the experience of the
      Ghent University Hospital fertility centre with Dutch and French patients and
      tries to set out standards of care for CBRC patients. Dutch patients usually have
      longer histories, more complex pathology and are better informed, more outspoken
      and more financially secure. Thus, the care for these patients is challenging.
      The standards of care should be the same for local patients and CBRC patients;
      however, the nature of the complexity of the problems they come with will
      necessitate more time investment. Experience shows that many patients who have no
      access to treatment in their own country obtain reasonably good results. Some of
      them, however, are beyond possible help and these patients need a high standard
      of psychological care. All should be done to avoid that cross-border patients
      compromise the local care system. Special arrangements should be taken to manage
      possible complications following treatment.

PMID- 21945266
TI  - Eggs-ploiting women: a critical feminist analysis of the different principles in
      transplant and fertility tourism.
AB  - Intergovernmental agencies have recognized that inconsistencies in the way that
      nation states regulate commerce in human kidneys lubricate transplant tourism,
      and have repeatedly exhorted recalcitrant governments of both organ-importing and
      organ-exporting nations to criminalize the exchange of cash for kidneys. Yet
      these same organizations have elected to remain silent on inconsistencies in the
      regulation of the trade in human eggs that lubricate fertility tourism. This
      article is a critical feminist analysis of this paradox. Sketches of the
      histories of regulation of the global markets in human kidneys and human eggs
      allow attribution of the different approaches to sales of kidneys and eggs to the
      triumph of neo-liberalism in the 1990s. Neo-liberalism supports the growth of the
      medical tourism industry and its niche market catering for infertility, and is
      responsible for exacerbating the relative disadvantage of poor and powerless
      women in destination countries, thereby creating the conditions for
      'bioavailability', that is, the willingness to exchange body parts for cash. The
      paper identifies a disturbing correlation between deeply engrained conservative
      attitudes to women and a plentiful supply of eggs, and concludes by suggesting
      that what women need to lift themselves out of poverty and discrimination is
      secure and dignified work.

PMID- 21945267
TI  - Reverse traffic: intersecting inequalities in human egg donation.
AB  - The paper examines a case of cross-border reproductive care that happens in
      reverse by looking at Israeli--Romanian transnational ova traffic. The state of
      Israel claims to have the most IVF clinics per capita in the world, some of the
      highest success rates in the use of assisted reproductive technology, very
      liberal regulation of these technologies and the most heavily subsidized IVF in
      the world. This support and the government's demographic policies are designed to
      encourage the growth of the Jewish population in its demographic race against
      Palestinians. Yet transnational egg donation is very costly and reimbursement to
      patients a slow and involved process. Hence, while transnational ova donation is
      increasing in Israel, only a few can afford to participate in this border
      crossing. Further, new laws are meant to forbid cross-religious donation in
      Israel, hardening the borders of the Jewish State. Romanian ova donors are part
      of the global majority, exploited by markets' incursions into new niches in
      bodies. The history of Romanian oppression of women's reproduction makes today's
      women willing to undergo invasive treatment for very little compensation, even
      when there is the possibility of injury. This paper documents reverse traffic
      reproduction, which maintains, rather than addresses, inequalities.

PMID- 21945268
TI  - Purification and characterization of Plasmodium yoelii adenosine deaminase.
AB  - Plasmodium lacks the de novo pathway for purine biosynthesis and relies
      exclusively on the salvage pathway. Adenosine deaminase (ADA), first enzyme of
      the pathway, was purified and characterized from Plasmodium yoelii, a rodent
      malarial species, using ion exchange and gel exclusion chromatography. The
      purified enzyme is a 41 kDa monomer. The enzyme showed K(m) values of 41 MUM and
      34 MUM for adenosine and 2'-deoxyadenosine, respectively. Erythro-9-(2-hydroxy-3
      nonyl) adenine competitively inhibited P. yoelii ADA with K(i) value of 0.5 MUM.
      The enzyme was inhibited by DEPC and protein denaturing agents, urea and GdmCl.
      Purine analogues significantly inhibited ADA activity. Inhibition by p
      chloromercuribenzoate (pCMB) and N-ethylmaleimide (NEM) indicated the presence of
      functional -SH groups. Tryptophan fluorescence maxima of ADA shifted from 339 nm
      to 357 nm in presence of GdmCl. Refolding studies showed that higher GdmCl
      concentration irreversibly denatured the purified ADA. Fluorescence quenchers (KI
      and acrylamide) quenched the ADA fluorescence intensity to the varied degree. The
      observed differences in kinetic properties of P. yoelii ADA as compared to the
      erythrocyte enzyme may facilitate in designing specific inhibitors against ADA.

PMID- 21945269
TI  - Isolation and detection of Leishmania species among naturally infected Rhombomis
      opimus, a reservoir host of zoonotic cutaneous leishmaniasis in Turkemen Sahara,
      North East of Iran.
AB  - In Iran, three species of Leishmania have been incriminated as the causative
      agents of human leishmaniasis, Leishmania (L.) major, Leishmania tropica, and
      Leishmania infantum.Rhombomis opimus have been incriminated as a principal
      reservoirs of the parasitic protozoan Leishmania major, the causative agent of
      rural zoonotic cutaneous leishmaniasis (ZCL) in Iran. Rodents captured and
      examined to find Leishmania species using conventional methods including direct
      impression smear and microscopic observation inoculation samples to Balb/c and
      culture in NNN medium. Also molecular method was employed to detect Leishmania in
      rodents by amplifying a region of the ribosomal RNA amplicon of Leishmania (ITS1
      5.8S rRNA-ITS2) using Nested PCR. Leshmania species were specified by DNA
      sequences. 36 (38.3%) of R. opimus were Leishmania positive using at least one
      conventional methods. Many more ITS-rDNA fragments were amplified from R. opimus
      but only 65 out of 74 PCR products contained enough DNA for direct sequencing or
      readable sequences. The PCR assays detected in Iranian R. opimus not only
      Leishmania major in 59 (79.7%) rodents but also Leishmania turanica in 6 (8.1%)
      rodents, another parasite of the great gerbil. These parasites were found in
      Turkemen Sahara, North East of Iran, in a focus of rural (ZCL). L. major and L.
      turanica in R. opimus firmly identified from Turkemen Sahara. Nine rodents with
      Leishmania infections unidentified which some were unreadable sequences, these
      could be mixed infections of L. major, L. turanica, Leishmania gerbillisensu lato
      and Leishmania close to L. gerbilli or a related species reported in sandflies
      previously from this location. The haplotypes of L. major and L. turanica were
      found to be identical to that of isolates of L. major and L. turanica from Iran
      and in GenBank elsewhere. R. opimus is probably the key reservoir in this ZCL
      focus because of its abundance and its infection rates with both L. major and L.
      turanica.

PMID- 21945270
TI  - Stability of polylactic acid particles and release of fluorochromes upon topical
      application on human skin explants.
AB  - Particle-based drug delivery systems allow the controlled and targeted release of
      incorporated active compounds to the skin and are promising tools to improve the
      efficacy of topical therapies. In this study we investigated the stability and
      release properties of biodegradable polylactic acid (PLA) particles upon topical
      application on human skin explants. PLA particles loaded with the hydrophilic
      fluorochrome 4-Di-2-Asp (DiAsp-PLA) were compared to PLA particles loaded with
      the lipophilic fluorochrome Bodipy 630/650 (BP-PLA). Changes of the particle
      morphology after their incubation on skin surface were investigated by means of
      electron microscopy while fluorescence microscopy and flow cytometry were used to
      evaluate particle penetration in hair follicles and fluorochrome release. We
      found that BP-PLA particles released rapidly the loaded fluorochrome and lost the
      particulate morphology within a few hours after application on skin surface. On
      the contrary, DiAsp-PLA particles maintained the particulate morphology,
      accumulated in hair follicles, and allowed a constant release of the incorporated
      fluorochrome for up to 16 h. These results show that, once applied to skin
      surface, PLA particles release the incorporated fluorochromes in a time-dependent
      manner and suggest the perspective to modulate particle stability and release
      properties by incorporating excipients with different degree of lipophilicity.

PMID- 21945271
TI  - Development of a novel model for comparative evaluation of intranasal
      pharmacokinetics and effects of anti-allergic nasal sprays.
AB  - For locally acting drugs, an extended residence time in the nasal cavity is
      desirable and related to a prolonged effect. We sought to develop a model for
      comparative determination of intranasal pharmacokinetics. We embedded human
      respiratory tissue into a solid matrix and coated the surface with artificial
      nasal fluid. Nasal spray suspensions of fluticasone propionate (FP) and
      budesonide (Bud) as well as a solution of azelastine hydrochloride (AZ) were
      applied onto the surface and removed after 30 min to simulate mucociliary
      clearance. As exemplary anti-inflammatory measure, we evaluated the inhibition of
      IL-8 release from epithelial cells. FP and Bud were initially bound to the same
      extent to the tissue gel while AZ displayed a more 4-fold higher binding than FP
      or Bud. After equilibrium with plasma, approximately 5-fold higher tissue
      concentrations of AZ compared to FP and 77-fold higher levels in relation to Bud
      were determined. This tissue retention revealed an excellent correlation with the
      volume of distribution of the respective drugs (r=0.9999, p <= 0.05). The
      inhibitory effect of FP on IL-8 release was approximately 5-fold more pronounced
      compared to AZ. The present model realistically mirrors conditions in vivo where
      solubility and tissue absorption of intranasally applied drugs compete with
      mucociliary clearance mechanisms.

PMID- 21945272
TI  - Awareness and knowledge of schistosomiasis infection and prevention in the "Three
      Gorges Dam" reservoir area: a cross-sectional study on local residents and health
      personnel.
AB  - BACKGROUND: Schistosomiasis is a severe public health problem in China. It has
      been predicted that the ecological changes caused by the "Three Gorges Dam", the
      world's largest hydropower project, could potentially aggravate the spread of
      schistosomiasis in the area. This study focused on investigating (a) local
      residents' knowledge on the potential risks of schistosomiasis and (b) the
      capability of local health personnel in preventing schistosomiasis. MATERIALS AND
      METHODS: A quantitative survey combined with qualitative interviews was conducted
      in three counties of the reservoir area during November and December 2008. A
      total of 1386 inhabitants and 180 local health personals participated in
      questionnaire survey; 18 inhabitants, 21 health professionals, and 8 local
      government officials were interviewed. RESULTS: Of the surveyed inhabitants,
      66.3% had no access to safe drinking water; 47.9% had water-contact regularly
      through farming or swimming; 58.7% did not have hygienic toilets; and only 13.7%
      used methane for energy. Besides, only 3.8% of the inhabitants had knowledge
      scores higher than 6 points within the range 0-10. Educational level, occupation
      and income were significant predictors of knowledge score (P<0.05). Only about 5%
      of the inhabitants had some knowledge on schistosomiasis. Among health
      professionals surveyed, 6.7% had college or higher education; 26.7% had prior
      schistosomiasis control experience; 75.6% did not receive any relevant training
      in the past year; and only 52.2% had basic knowledge of schistosomiasis. The
      logistic regression analysis identified occupation and time at work as
      significant factors to their knowledge level (P<0.05). Moreover, the surveillance
      work was often severely hindered by a shortage of funding, and challenged by
      monitoring of migrant population. There were very limited training opportunities
      for the health workers, and almost no health education for inhabitants, if any,
      neither efficient nor effective. CONCLUSION: Although there were multiple risks
      for potential Schistosoma japonicum infections in the study area, the knowledge
      level on schistosomiasis and surveillance was relatively low both in local
      residents and health personnel. Thus, more health education and professional
      training are urgently required to local residents and health personnel,
      respectively. By considering limited activities in surveillance and health
      education been implemented, a strategy plan on intervention to ensure a stronger
      inter-sectoral cooperation is recommended in order to reduce schistosomiasis
      transmission risks in this area.

PMID- 21945273
TI  - Hepatorenal findings in obligate heterozygotes for autosomal recessive polycystic
      kidney disease.
AB  - Autosomal recessive polycystic kidney disease (ARPKD), characterized by
      progressive cystic degeneration of the kidneys and congenital hepatic fibrosis
      (CHF), is the most common childhood onset ciliopathy, with an estimated frequency
      of 1 in 20,000 births. It is caused by mutations in PKHD1. The carrier frequency
      for ARPKD in the general population is estimated at 1 in 70. Given the recessive
      inheritance pattern, individuals who are heterozygous for PKHD1 mutations are not
      expected to have clinical findings. We performed ultrasound (USG) evaluations on
      110 parents from 64 independent ARPKD families and identified increased medullary
      echogenicity in 6 (5.5%) and multiple small liver cysts in 10 parents (9%). All
      ARPKD parents with these abnormal imaging findings were asymptomatic; kidney and
      liver function tests were unremarkable. Complete sequencing of PKHD1 in the 16
      ARPKD parents with abnormal imaging confirmed the mutation transmitted to the
      proband, but did not reveal any other pathogenic variants. Our data suggest that
      carrier status for ARPKD is a predisposition to polycystic liver disease and
      renal involvement associated with increased medullary echogenicity on USG.
      Whether some of these individuals become symptomatic as they age remains to be
      determined.

PMID- 21945274
TI  - In vivo optogenetic stimulation of neocortical excitatory neurons drives brain
      state-dependent inhibition.
AB  - BACKGROUND: Synaptic interactions between excitatory and inhibitory neocortical
      neurons are important for mammalian sensory perception. Synaptic transmission
      between identified neurons within neocortical microcircuits has mainly been
      studied in brain slice preparations in vitro. Here, we investigate brain-state
      dependent neocortical synaptic interactions in vivo by combining the specificity
      of optogenetic stimulation with the precision of whole-cell recordings from
      postsynaptic excitatory glutamatergic neurons and GFP-labeled inhibitory
      GABAergic neurons targeted through two-photon microscopy. RESULTS:
      Channelrhodopsin-2 (ChR2) stimulation of excitatory layer 2/3 barrel cortex
      neurons evoked larger and faster depolarizing postsynaptic potentials and more
      synaptically driven action potentials in fast-spiking (FS) GABAergic neurons
      compared to both non-fast-spiking (NFS) GABAergic neurons and postsynaptic
      excitatory pyramidal neurons located within the same neocortical microcircuit.
      The number of action potentials evoked in ChR2-expressing neurons showed low
      trial-to-trial variability, but postsynaptic responses varied strongly with near
      linear dependence upon spontaneously driven changes in prestimulus membrane
      potential. Postsynaptic responses in excitatory neurons had reversal potentials,
      which were hyperpolarized relative to action potential threshold and were
      therefore inhibitory. Reversal potentials measured in postsynaptic GABAergic
      neurons were close to action potential threshold. Postsynaptic inhibitory neurons
      preferentially fired synaptically driven action potentials from spontaneously
      depolarized network states, with stronger state-dependent modulation in NFS
      GABAergic neurons compared to FS GABAergic neurons. CONCLUSIONS: Inhibitory
      neurons appear to dominate neocortical microcircuit function, receiving stronger
      local excitatory synaptic input and firing more action potentials compared to
      excitatory neurons. In mouse layer 2/3 barrel cortex, we propose that strong
      state-dependent recruitment of inhibitory neurons drives competition among
      excitatory neurons enforcing sparse coding.

PMID- 21945275
TI  - Reconstructing visual experiences from brain activity evoked by natural movies.
AB  - Quantitative modeling of human brain activity can provide crucial insights about
      cortical representations [1, 2] and can form the basis for brain decoding devices
      [3-5]. Recent functional magnetic resonance imaging (fMRI) studies have modeled
      brain activity elicited by static visual patterns and have reconstructed these
      patterns from brain activity [6-8]. However, blood oxygen level-dependent (BOLD)
      signals measured via fMRI are very slow [9], so it has been difficult to model
      brain activity elicited by dynamic stimuli such as natural movies. Here we
      present a new motion-energy [10, 11] encoding model that largely overcomes this
      limitation. The model describes fast visual information and slow hemodynamics by
      separate components. We recorded BOLD signals in occipitotemporal visual cortex
      of human subjects who watched natural movies and fit the model separately to
      individual voxels. Visualization of the fit models reveals how early visual areas
      represent the information in movies. To demonstrate the power of our approach, we
      also constructed a Bayesian decoder [8] by combining estimated encoding models
      with a sampled natural movie prior. The decoder provides remarkable
      reconstructions of the viewed movies. These results demonstrate that dynamic
      brain activity measured under naturalistic conditions can be decoded using
      current fMRI technology.

PMID- 21945276
TI  - MRI magnetic field stimulates rotational sensors of the brain.
AB  - Vertigo in and around magnetic resonance imaging (MRI) machines has been noted
      for years [1, 2]. Several mechanisms have been suggested to explain these
      sensations [3, 4], yet without direct, objective measures, the cause is unknown.
      We found that all of our healthy human subjects developed a robust nystagmus
      while simply lying in the static magnetic field of an MRI machine. Patients
      lacking labyrinthine function did not. We use the pattern of eye movements as a
      measure of vestibular stimulation to show that the stimulation is static
      (continuous, proportional to static magnetic field strength, requiring neither
      head movement nor dynamic change in magnetic field strength) and directional
      (sensitive to magnetic field polarity and head orientation). Our calculations and
      geometric model suggest that magnetic vestibular stimulation (MVS) derives from a
      Lorentz force resulting from interaction between the magnetic field and naturally
      occurring ionic currents in the labyrinthine endolymph fluid. This force pushes
      on the semicircular canal cupula, leading to nystagmus. We emphasize that the
      unique, dual role of endolymph in the delivery of both ionic current and fluid
      pressure, coupled with the cupula's function as a pressure sensor, makes magnetic
      field-induced nystagmus and vertigo possible. Such effects could confound
      functional MRI studies of brain behavior, including resting-state brain activity.

PMID- 21945277
TI  - Cyclin-specific docking motifs promote phosphorylation of yeast signaling
      proteins by G1/S Cdk complexes.
AB  - BACKGROUND: The eukaryotic cell cycle begins with a burst of cyclin-dependent
      kinase (Cdk) phosphorylation. In budding yeast, several Cdk substrates are
      preferentially phosphorylated at the G1/S transition rather than later in the
      cell cycle when Cdk activity levels are high. These early Cdk substrates include
      signaling proteins in the pheromone response pathway. Two such proteins, Ste5 and
      Ste20, are phosphorylated only when Cdk is associated with the G1/S cyclins Cln1
      and Cln2 and not G1, S, or M cyclins. The basis of this cyclin specificity is
      unknown. RESULTS: Here we show that Ste5 and Ste20 have recognition sequences, or
      "docking" sites, for the G1/S cyclins. These docking sites, which are distinct
      from Clb5/cyclin A-binding "RXL" motifs, bind preferentially to Cln2. They
      strongly enhance Cln2-driven phosphorylation of each substrate in vivo and
      function largely independent of position and distance to the Cdk sites. We
      exploited this functional independence to rewire a Cdk regulatory circuit in a
      way that changes the target of Cdk inhibition in the pheromone response pathway.
      Furthermore, we uncover functionally active Cln2 docking motifs in several other
      Cdk substrates. The docking motifs drive cyclin-specific phosphorylation, and the
      cyclin preference can be switched by using a distinct motif. CONCLUSIONS: Our
      findings indicate that some Cdk substrates are intrinsically capable of being
      phosphorylated by several different cyclin-Cdk forms, but they are inefficiently
      phosphorylated in vivo without a cyclin-specific docking site. Docking
      interactions may play a prevalent but previously unappreciated role in driving
      phosphorylation of select Cdk substrates preferentially at the G1/S transition.

PMID- 21945278
TI  - Tyrosinase expression during black truffle development: from free living mycelium
      to ripe fruit body.
AB  - The present work studies the expression of tyrosinase (monophenol:diphenol oxygen
      oxidoreductase, EC 1.14.18.1) during the development of the black truffle Tuber
      melanosporum Vittad., an ectomycorrhizal fungus of great biological and economic
      interest. As widely reported in the literature, melanins and the enzymes that
      synthesize them, are of paramount importance in fungal development and sexual
      differentiation. Tyrosinase and laccase are the enzymes that produce melanins
      from monophenols and diphenols. We have detected tyrosinase expression from the
      stage of free living mycelium, through the mychorrizal stage and the six fruit
      body developmental stages by measuring the levels of tyrosinase mRNA by
      quantitative PCR (q-PCR), spectrophotometry, histochemistry, immunohistochemistry
      and electrophoresis. Tyrosinase is always expressed, from the free living
      mycelium to the ripe fruit body developmental stages, when it is very low. The
      switching off of the tyrosinase gene during T. melanosporum development when the
      fruit body is ripe and no more cell walls are to be built is discussed in
      relation of thioflavour production. Specific primers, prepared from the cloned T.
      melanosporum tyrosinase cDNA were used for the q-PCR and the deduced aminoacid
      sequences of the CuA and CuB binding sites were compared to those of various
      ascomycetes and basidiomycetes.

PMID- 21945279
TI  - Leiomyosarcoma of the corpus cavernosum mimicking a Peyronie's plaque.
AB  - Peyronie's disease is relatively frequent and can cause pain and penile
      induration. Penile soft tissue tumors, however, are exceptional, with fewer than
      45 cases reported since 1930. Some clinical and imagery elements could lead to
      earlier diagnosis through biopsy, enabling more extensive resections and,
      ultimately, better prognosis.

PMID- 21945280
TI  - An unusual cause of an enhancing retroperitoneal mass.
AB  - We report an important and unusual cause of an enhancing retroperitoneal
      paracaval mass. Ten years after vena cava filter (VCF) placement, a 3.5-cm mass
      was found juxtaposed to the right kidney and vena cava. Open exploration
      demonstrated a venous variceal mass with perforation of the VCF through the wall
      of the vena cava, requiring vena cava resection and graft replacement. This is an
      infrequently described, potentially misleading and dangerous complication of vena
      cava filters. Better guidelines for such filters would be useful. We recommend an
      open approach in settings that could require similarly complex reconstructions.

PMID- 21945281
TI  - Does a controversial topic affect the quality of urologic information on the
      Internet?
AB  - OBJECTIVE: Increasingly, patients seek medical information via the Internet,
      despite highly variable information quality. We sought to determine whether
      controversial urological topics are associated with decreased content quality or
      search characteristics. METHODS: We systematically searched the Internet for 5
      noncontroversial (cryptorchidism, testicular torsion, urethral stricture,
      testicular cancers, renal cancers) and 5 controversial (disorders of sexual
      differentiation, circumcision, penile elongation, interstitial cystitis,
      testosterone therapy) conditions. Number of total hits, sponsored links, page
      owner and author, accreditation, updates, advertising, readability, and content
      quality were assessed for each topic. Content quality was determined on a 5-point
      scale for accuracy and completeness of 3 domains: diagnosis, natural history, and
      treatment. RESULTS: In total, 100 websites were evaluated. Noncontroversial
      topics had more hits (1,610,000 vs 475,000) and more sponsored links (30% vs 10%)
      than controversial topics. Noncontroversial web pages were more likely to have
      government or medical owners (58% vs 30%, P = .009) than controversial web pages.
      Website quality was significantly different between noncontroversial and
      controversial topics. In regard to accuracy, noncontroversial topics had higher
      scores for diagnosis (4.6 vs 3.8, P <.0001), natural history (4.5 vs 3.2, P
      <.0001), and treatment (4.6 vs 3.3, P <.0001). Similarly, noncontroversial topics
      had higher completeness scores for diagnosis (3.8 vs 3.0, P = .001), natural
      history (3.7 vs 3.0, P = .003), and treatment (3.6 vs 3.0, P = .006). CONCLUSION:
      Web pages dedicated to controversial urological topics have lower quality content
      in regard to diagnosis, natural history, and treatment. Such quality issues may
      contribute to ongoing public confusion and misinformation regarding these
      challenging topics.

PMID- 21945282
TI  - Bicycle-related genitourinary injuries.
AB  - OBJECTIVE: To use the National Trauma Data Bank (NTDB) to evaluate bicycling
      related genitourinary (GU) injury. Bicycling is a popular recreational and
      competitive sport with recognized risks. GU injuries associated with bicycling is
      unknown. METHODS: Patient cases were extracted from the NTDB, version 9.1, using
      the mechanism of injury Ecode for pedal cyclist and ICD-9 codes for GU injuries.
      The type of GU injuries, patient demographics, Injury Severity Score, surgical
      management, outcomes, and disposition were analyzed. RESULTS: Of 635,013 trauma
      cases evaluated, 16,585 were identified as trauma because of bicycle injury. GU
      injuries were sustained in 358 (2%) patients; 86% were male, with a mean age of
      29 years. The most commonly injured GU organ was the kidney (75%), followed by
      bladder and urethra (15%), and penis and scrotum (10%). These injuries resulted
      in nephrectomy (0.4%), cystorrhaphy (11.3%), scrotorrhaphy (42.1%), testicular
      repair (3.1%), and penile repair (7.5%). Most common associated injuries included
      vertebral fracture (35%), pelvic fracture (25%), spleen (19%), and open head
      wound (15%). Patients who sustained a vertebral fracture commonly sustained a
      concomitant bladder and urethra (37.7%) or a renal injury (22.6%). CONCLUSION: GU
      injury is an infrequent occurrence with bicycle trauma, occurring in 2% of
      bicycle injuries, with kidneys being the most commonly injured GU organ.
      Physicians treating bicyclists who sustained a vertebral fracture should be aware
      of a possible concomitant renal or bladder injury. Young males appear to be
      principally at risk for GU injury.

PMID- 21945283
TI  - Combining symmetry elements results in potent naphthyridinone (NTD) HIV-1
      integrase inhibitors.
AB  - A series of naphthyridinone HIV-1 integrase strand-transfer inhibitors have been
      designed based on a psdeudo-C2 symmetry element present in the two-metal
      chelation pharmacophore. A combination of two distinct inhibitor binding modes
      resulted in potent inhibition of the integrase strand-transfer reaction in the
      low nM range. Effects of aryl and N1 substitutions are disclosed including the
      impact on protein binding adjusted antiviral activity.

PMID- 21945284
TI  - Discovery of novel 3,5-disubstituted indole derivatives as potent inhibitors of
      Pim-1, Pim-2, and Pim-3 protein kinases.
AB  - A series of novel 3,5-disubstituted indole derivatives as potent and selective
      inhibitors of all three members of the Pim kinase family is described. High
      throughput screen identified a pan-Pim kinase inhibitor with a promiscuous
      scaffold. Guided by structure-based drug design, SAR of the series afforded a
      highly selective indole chemotype that was further developed into a potent set of
      compounds against Pim-1, 2, and 3 (Pim-1 and Pim-3: IC(50)<=2nM and Pim-2:
      IC(50)<=100nM).

PMID- 21945285
TI  - Drug targeting to tumors: principles, pitfalls and (pre-) clinical progress.
AB  - Many different systems and strategies have been evaluated for drug targeting to
      tumors over the years. Routinely used systems include liposomes, polymers,
      micelles, nanoparticles and antibodies, and examples of strategies are passive
      drug targeting, active drug targeting to cancer cells, active drug targeting to
      endothelial cells and triggered drug delivery. Significant progress has been made
      in this area of research both at the preclinical and at the clinical level, and a
      number of (primarily passively tumor-targeted) nanomedicine formulations have
      been approved for clinical use. Significant progress has also been made with
      regard to better understanding the (patho-) physiological principles of drug
      targeting to tumors. This has led to the identification of several important
      pitfalls in tumor-targeted drug delivery, including I) overinterpretation of the
      EPR effect; II) poor tumor and tissue penetration of nanomedicines; III)
      misunderstanding of the potential usefulness of active drug targeting; IV)
      irrational formulation design, based on materials which are too complex and not
      broadly applicable; V) insufficient incorporation of nanomedicine formulations in
      clinically relevant combination regimens; VI) negligence of the notion that the
      highest medical need relates to metastasis, and not to solid tumor treatment;
      VII) insufficient integration of non-invasive imaging techniques and
      theranostics, which could be used to personalize nanomedicine-based therapeutic
      interventions; and VIII) lack of (efficacy analyses in) proper animal models,
      which are physiologically more relevant and more predictive for the clinical
      situation. These insights strongly suggest that besides making ever more
      nanomedicine formulations, future efforts should also address some of the
      conceptual drawbacks of drug targeting to tumors, and that strategies should be
      developed to overcome these shortcomings.

PMID- 21945286
TI  - European 2--a clonal complex of Mycobacterium bovis dominant in the Iberian
      Peninsula.
AB  - Mycobacterium bovis isolates from the Iberian Peninsula are dominated by strains
      with spoligotype patterns deleted for spacer 21. Whole-genome sequencing of three
      Spanish strains with spacer 21 missing in their spoligotype pattern revealed a
      series of SNPs and subsequent screening of a selection of these SNPs identified
      one in gene guaA that is specific to these strains. This group of strains from
      the Iberian Peninsula missing spoligotype spacer 21 represents a new clonal
      complex of M. bovis, defined by the SNP profile with a distinct spoligotype
      signature. We have named this clonal complex European 2 (Eu2) and found that it
      was present at low frequency in both France and Italy and absent from the British
      Isles.

PMID- 21945287
TI  - Increased expression of the Vesicular Glutamate Transporter-1 (VGLUT1) in the
      prefrontal cortex correlates with differential vulnerability to chronic stress in
      various mouse strains: effects of fluoxetine and MK-801.
AB  - Major depression is a chronic psychiatric illness that is highly prevalent and
      disabling. The available medications are ineffective for many patients suggesting
      that differents molecular pathways could be specifically altered in the
      unresponsive patients. Recently, the glutamatergic system has emerged as a target
      in the research on depression and acute NMDA receptor blockade has been shown to
      produce strong antidepressant effects. We have studied the adaptations of four
      mice strains (C57BL/6, DBA/2, C3H and BALB/c) to a chronic unpredictable stress
      protocol, a widely used model of depression in rodents. BALB/c mice displayed
      strikingly different behavioral and neurochemical adaptations compared to the
      other strains tested, suggesting that different molecular pathways are involved
      in their specific vulnerability. They became hyperactive during the dark period,
      anhedonic-like and displayed no alterations in the tail suspension test (TST).
      After chronic stress, only the BALB/c displayed an increased frontocortical
      VGLUT1 expression which is suggestive of a dysregulation of their prefrontal
      glutamatergic system, and no BDNF mRNA alteration, although the acute stress
      modulation of this mRNA is similar to the other strains. Chronic administration
      of an antagonist of NMDA receptors, MK-801, induced antidepressant-like effects
      in the TST for stressed BALB/c, but was ineffective for the hyperactivity and
      anhedonia-like behavior, in contrast to fluoxetine. Chronic MK-801 was totally
      inactive on the behavior of stressed C57BL/6 mice. MK-801, but not fluoxetine,
      inhibited the VGLUT1 prefrontal increase in BALB/c. Fluoxetine increased VGLUT1
      and BDNF mRNA expression in the hippocampus of the C57BL/6 but not in the BALB/c
      strain, suggesting a different reactivity in-between strain to both stress and
      antidepressant. Interestingly enough, the BDNF or VGLUT1 increase is not
      necessary to reverse the stress induced behavioral alterations in our
      experimental settings. This observation supports the conclusion that BDNF and
      VGLUT1 are depressive state markers, but not involved in its etiology. Finally,
      there is a substantial similarity between the phenotypes that are observed in the
      BALB/c mice and endogenous depression in humans, as well as between C57BL/6 mice
      and atypical depression. To have a better understanding of the variability of
      depression etiologies in human, and the implication of the glutamatergic system,
      it may be suggested that future animal studies in the mouse would systematically
      compare the two strains BALB/c and C57BL/6 for the identification of relevant
      biological mechanisms. This article is part of a special Issue entitled 'Anxiety
      and Depression'.

PMID- 21945288
TI  - Virogenetic and optogenetic mechanisms to define potential therapeutic targets in
      psychiatric disorders.
AB  - A continuously increasing body of knowledge shows that the brain is an extremely
      complex neural network and single neurons possess their own complicated
      interactive signaling pathways. Such complexity of the nervous system makes it
      increasingly difficult to investigate the functions of specific neural components
      such as genes, proteins, transcription factors, neurons and nuclei in the brain.
      Technically, it has been even more of a significant challenge to identify the
      molecular and cellular adaptations that are both sufficient and necessary to
      underlie behavioral functions in health and disease states. Defining such neural
      adaptations is a critical step to identify the potential therapeutic targets
      within the complex neural network that are beneficial to treat psychiatric
      disorders. Recently, the new development and extensive application of in vivo
      viral-mediated gene transfer (virogenetics) and optical manipulation of specific
      neurons or selective neural circuits in freely-moving animals (optogenetics) make
      it feasible, through loss- and gain-of-function approaches, to reliably define
      sufficient and necessary neuroadaptations in the behavioral models of psychiatric
      disorders, including drug addiction, depression, anxiety and bipolar disorders.
      In this article, we focus on recent studies that successfully employ these
      advanced virogenetic and optogenetic techniques as a powerful tool to identify
      potential targets in the brain, and to provide highly useful information in the
      development of novel therapeutic strategies for psychiatric disorders. This
      article is part of a Special Issue entitled 'Anxiety and Depression'.

PMID- 21945289
TI  - Hippocampal GR expression is increased in elderly depressed females.
AB  - Hyperactivity of the Hypthalamus-Pituitary-Adrenal (HPA)-axis is common in major
      depression and evident from e.g., a frequently exaggerated response to combined
      application of dexamethasone and CRH in this disorder. HPA-axis activity and
      hence the secretion of glucocorticoids (GC), the endpoint of the HPA-axis,
      depends to some extent on GC binding to glucocorticoid receptors (GR) that are
      abundantly expressed in the hippocampus. To assess whether differences in
      hippocampal GR expression occur in association with depression, we investigated
      GR-alpha protein immunoreactivity (ir) in postmortem hippocampal tissue of an
      elderly cohort of 9 well-characterized depressed patients and 9 control subjects
      that were pair-wise matched for age, sex, CSF-pH and postmortem delay. Abundant
      nuclear GR-ir was observed in neurons of the hippocampal Ammon's horn (CA) and
      dentate gyrus (DG) subregions. GR-ir in the DG correlated positively with age in
      the depressed but not the control group. Although no significant differences were
      found in GR-ir between the depressed and control groups, a significant increase
      in GR-ir was present in depressed females compared to depressed males. Whether
      this sex difference in hippocampal GR-ir in depression relates to the increased
      incidence of depression in females awaits further study. This article is part of
      a Special Issue entitled 'Anxiety and Depression'.

PMID- 21945291
TI  - Prophylactic lithium alleviates postoperative cognition impairment by
      phosphorylating hippocampal glycogen synthase kinase-3beta (Ser9) in aged rats.
AB  - Postoperative cognition impairment is a perishing complication in elderly
      patients undergone surgeries. Lithium is widely used in psychiatric patients for
      its role in neuronal protection, whereas whether or not it could attenuate
      surgery-associated postoperative cognition dysfunction used prophylactically is
      not well defined. After approval by the Institutional Animal Care and Use
      Committee, 48 male Sprague-Dawley rats aged 18months old were randomly divided
      into three groups with 16 each: i, no surgeries and drugs were given; ii,
      surgical procedures were performed only without drug delivery; iii, prophylactic
      2mM/kg lithium chloride was given intraperitoneally once a day for seven days
      before surgeries. The change in spatial memory was assessed with Morris Water
      Maze (MWM), and the activation of PI3K/AKT/mTOR pathway was detected, and the
      levels of hippocampal glycogen synthase kinase-3beta (p-GSK-3beta)
      phosphorylation at serine 9 and interleukin-1beta (IL-1beta) were measured. The
      MWM detection showed that both swimming latency and distance were considerably
      prolonged by the surgeries, but these changes could be markedly shortened by
      prophylactic lithium administration. Meanwhile, the changes in the hippocampal
      PI3K cascades and p-GSK-3beta and IL-1beta expression displayed corresponding
      changes that were parallel to the alterations of spatial memory, and inhibition
      of PI3K and GSK-3beta suggested upstream PI3K activation leads to downstream
      change in p-GSK-3beta and IL-1beta. These results indicate, at least in part,
      that prophylactic lithium can alleviate surgery-associated impairment of the
      spatial memory in aged rats which is strongly associated with the reduced levels
      of hippocampal p-GSK-3beta and IL-1beta resulted from the activation of
      PI3K/AKT/mTORC2 pathway.

PMID- 21945292
TI  - A modelling approach to predict the variation of repeatability and
      reproducibility of a RT-PCR assay for infectious salmon anaemia virus across
      infection prevalences and infection stages.
AB  - Conventional studies on the precision of diagnostic tests with binary outcomes
      report single descriptive estimates of agreement for a particular pool of
      samples. However, agreement for binary tests is intrinsically associated with the
      assay operating characteristics that are influenced by population and laboratory
      covariate factors. Therefore, reporting agreement estimates under various
      conditions may be more appropriate for diagnostic test comprehension. In this
      study, the influence of various submission factors (tissue sample homogenization,
      prevalence of infection and pathogen level) on agreement was further analyzed
      using test result information from a previous descriptive report of within and
      between laboratories agreement (repeatability and reproducibility, respectively)
      of a Reverse-Transcription Polymerase Chain Reaction (RT-PCR) assay for
      infectious salmon anaemia virus (ISAV). Multilevel logistic regression models
      were constructed separately for non-, low- or high-infected salmon (classified
      using a study pseudogold standard) to predict probabilities of testing positive
      under different testing conditions. For each of the 3 infection categories,
      agreement and kappa values within and between laboratories were computed from the
      models' predicted values using probability formulae. Thereafter, overall
      estimates were predicted using simple category weighting for various proportions
      of infection stages. Agreement varied substantially among infection categories
      and, consequently, overall repeatability and reproducibility varied greatly with
      prevalence. This confirmed that the report of a single descriptive estimate
      (corresponding to a set prevalence) may not be appropriate. Low-infected fish had
      the lowest agreement estimate which was improved by sample homogenization. This
      supported a heterogeneous distribution of ISAV in early infected salmon kidney.
      However, tissue homogenization increased the probability to obtain a false
      positive test result (cross-contamination suspected) and decreased agreement in
      non-infected fish. Compared to conventional report of test agreement estimation,
      the modelling approach identified influencing submission factors and provided
      predictive intervals of agreement that give a better expectation and
      understanding of assay repeatability and reproducibility under different
      circumstances of use.

PMID- 21945293
TI  - Influence of a marine algae supplementation on the oxidative status of plasma in
      dairy cows during the periparturient period.
AB  - This study was part of a larger study that addressed the effects of marine algae
      (ALG) supplementation in the ration of high yielding periparturient dairy cows.
      The objectives were to induce milk fat depression (MFD) in early lactation by
      feeding docosahexaenoic acid (DHA) from ALG and to determine the effects on milk
      production, milk components and metabolic status early post partum. This study
      focuses on the oxidative status in the plasma during the ALG supplementation.
      Plasma samples were collected from 16 Holstein Friesian cows at the day of
      parturition and at -1, 2, 4 and 6 weeks relative to calving with half of the cows
      receiving the ALG supplement (44gDHA/d) from 3 weeks pre partum on. The following
      parameters were measured in plasma: ferric reducing ability of plasma (FRAP),
      alpha-tocopherol level, glutathione peroxidase activity (GSH-Px) and
      thiobarbituric acid reactive substances (TBARS) concentration. There was a
      significant effect of time for FRAP and alpha-tocopherol indicating changes in
      the plasma oxidative status around parturition. The ALG supplementation was
      successful in creating a milk fat depression (MFD) but could not improve the
      energy balance. Feeding of ALG significantly increased lipid peroxidation as
      measured by TBARS, probably through their high content of n-3 polyunsaturated
      fatty acids.

PMID- 21945290
TI  - The neurogenesis hypothesis of affective and anxiety disorders: are we mistaking
      the scaffolding for the building?
AB  - Hypotheses are scaffoldings erected in front of a building and then dismantled
      when the building is finished. They are indispensable for the workman; but you
      mustn't mistake the scaffolding for the building. Johann Wolfgang von Goethe. The
      neurogenesis hypothesis of affective disorders - in its simplest form -
      postulates that the generation of neurons in the postnatal hippocampal dentate
      gyrus is involved in the etiology and treatment efficacy of major depressive
      disorder (MDD). The hypothesis was established in the 1990s but was built on a
      broad foundation of earlier research on the hippocampus, serotonin and MDD. It
      has gone through several growth phases fueled by discoveries both correlative and
      causative in nature. Recently, the hypothesis has also been broadened to also
      include potential relevance for anxiety disorders, like post-traumatic stress
      disorder (PTSD). As any hypothesis should be, it has been tested and challenged,
      sometimes vigorously. Here we review the current standing of the neurogenesis
      hypothesis of affective and anxiety disorders, noting in particular how a central
      postulate - that decreased neurogenesis results in depression or anxiety - has,
      in general, been rejected. We also review the controversies on whether treatments
      for these disorders, like antidepressants, rely on intact neurogenesis for their
      efficacy, and the existence of neurogenesis-dependent and -independent effects of
      antidepressants. In addition, we review the implications that the hypothesis has
      for the response to stress, PTSD, and the neurobiology of resilience, and
      highlight our own work showing that adult-generated neurons are functionally
      important for the behavioral response to social stress. We conclude by
      emphasizing how advancements in transgenic mouse technology, rodent behavioral
      analyses, and our understanding of the neurogenesis process will allow us to
      refine our conclusions and perform ever more specific experiments. Such scrutiny
      is critical, since if we "mistake the scaffolding for the building" we could
      overlook opportunities for translational impact in the clinic. This article is
      part of a special Issue entitled 'Anxiety and Depression'.

PMID- 21945295
TI  - Range of motion in the upper and lower cervical spine in people with chronic neck
      pain.
AB  - Reduced cervical range of motion (ROM) is a common finding in people with neck
      pain. With few exceptions, only the angle between head and thorax has been
      measured. Our aim was to use an extended model to compare active cervical flexion
      and extension, separate for upper and lower cervical levels, between people with
      chronic non-traumatic neck pain and controls. We also investigated associations
      between ROM measures, symptoms and self-rated functioning. In this cross
      sectional study, 102 subjects with neck pain and 33 healthy controls
      participated. An electromagnetic tracker system was used to measure the
      kinematics to construct a three-segment model including the thorax, cervical
      spine and head. Neutral flexion/extension were defined at subjects' self-selected
      seated posture. We found that in the neck pain group, extension in the upper
      cervical levels and predominately flexion for the lower levels were reduced. The
      ratio between ROM for the upper and lower levels was altered in the neck pain
      group so that the lower levels contributed to a lesser extent to the total
      sagittal ROM compared to controls. These findings could not be explained by a
      greater forward head posture but must have other origins. For the neck pain
      group, ROM measures were weakly associated to pain and self-rated functioning.
      Altogether, this implies that using a three-segment model for assessment of ROM
      can be a valuable improvement for characterisation of patients and treatment
      evaluation.

PMID- 21945294
TI  - Systematic chromosomal deletion of bacterial ribosomal protein genes.
AB  - Detailed studies of ribosomal proteins (RPs), essential components of the protein
      biosynthetic machinery, have been hampered by the lack of readily accessible
      chromosomal deletions of the corresponding genes. Here, we report the systematic
      genomic deletion of 41 individual RP genes in Escherichia coli, which are not
      included in the Keio collection. Chromosomal copies of these genes were replaced
      by an antibiotic resistance gene in the presence of an inducible, easy-to
      exchange plasmid-born allele. Using this knockout collection, we found nine RPs
      (L15, L21, L24, L27, L29, L30, L34, S9, and S17) nonessential for survival under
      induction conditions at various temperatures. Taken together with previous
      results, this analysis revealed that 22 of the 54 E. coli RP genes can be
      individually deleted from the genome. These strains also allow expression of
      truncated protein variants to probe the importance of RNA-protein interactions in
      functional sites of the ribosome. This set of strains should enhance in vivo
      studies of ribosome assembly/function and may ultimately allow systematic
      substitution of RPs with RNA.

PMID- 21945296
TI  - Manual palpation of lumbo-pelvic landmarks: a validity study.
AB  - Manual palpation (MP) is commonly used for the assessment of patients with
      neuromusculoskeletal dysfunction. During assessment of lumbo-pelvic disorders in
      particular, it may be used not only to explore pain and resistance in the region,
      but also to evaluate the symmetry and movement quality of the area. Whilst
      reliability of MP has been extensively investigated, its validity remains
      relatively under researched. The aim of this study was to explore the accuracy of
      MP of lumbo-pelvic bony points. Ultrasound images of three bony landmarks [4th
      lumbar spinous process (L4), left and right posterior superior iliac spines
      (PSIS)] were acquired from models (n = 3) in the prone position and the points
      marked with an ultra-violet (UV) pen. Nine musculoskeletal physiotherapists were
      asked to identify the bony landmarks using MP. Measurements (mms) were taken
      between the UV marks and the palpators' marks. The mean error (standard
      deviation) (mm) for MP of L4, LPSIS, RPSIS were 15.63 (3.89), 20.07 (4.60), 20.59
      (2.79) respectively. Bland and Altman analysis gave a mean value of 0.173, with
      95% limits of agreement ranging from -27.8 to 26.3. This study suggests that MP
      of specific lumbo-pelvic bony points has limited validity.

PMID- 21945298
TI  - Involvement of tissue plasminogen activator "tPA" in ethanol-induced locomotor
      sensitization and conditioned-place preference.
AB  - Ethanol is one of the most abused drugs in the western societies. It is well
      established that mesolimbic dopaminergic neurons mediate the rewarding properties
      of ethanol. In our previous studies we have shown that the serine protease tissue
      plasminogen activator (tPA) is involved in the rewarding properties of morphine
      and amphetamine. In the current study, we investigated the role of tPA in ethanol
      induced behavioral sensitization and conditioned-place preference (CPP). Ethanol
      treatment dose-dependently induced tPA enzymatic activity in the nucleus
      accumbens (NAc). In addition, ethanol-induced increase in tPA activity was
      completely inhibited by pre-treatment with the dopamine D1 and D2 receptor
      antagonists SCH23390 and raclopride respectively. Furthermore, ethanol-induced
      locomotor stimulation, behavioral sensitization and conditioned-place preference
      were enhanced following tPA over-expression in the NAc using a lentiviral vector.
      In contrast, tPA knock down in the NAc with specific shRNA blocked the rewarding
      properties of ethanol. The defect of locomotor stimulation in shRNA-injected mice
      was reversed by microinjections of exogenous recombinant tPA into the nucleus
      accumbens. Collectively, these results indicate, for the first time, that
      activation of tPA is effective in enhancing the rewarding effects of ethanol.
      Targeting the tissue plasminogen activator system would provide new therapeutic
      approaches to the treatment of alcoholism.

PMID- 21945297
TI  - Acetylcholine from the mesopontine tegmental nuclei differentially affects
      methamphetamine induced locomotor activity and neurotransmitter levels in the
      mesolimbic pathway.
AB  - Methamphetamine (MA) increases dopamine (DA) levels within the mesolimbic pathway
      and acetylcholine (ACh), a neurotransmitter known to increase DA cell firing and
      release and mediate reinforcement, within the ventral tegmental area (VTA). The
      laterodorsal tegmental (LDT) and pedunculopontine tegmental (PPT) nuclei provide
      cholinergic input to the VTA; however, the contribution of LDT- and PPT-derived
      ACh to MA-induced DA and ACh levels and locomotor activation remains unknown. The
      first experiment examined the role of LDT-derived ACh in MA locomotor activation
      by reversibly inhibiting these neurons with bilateral intra-LDT microinjections
      of the M2 receptor agonist oxotremorine (OXO). Male C57BL/6J mice were given a
      bilateral 0.1MUl OXO (0, 1, or 10nM/side) microinjection immediately prior to IP
      saline or MA (2mg/kg). The highest OXO concentration significantly inhibited both
      saline- and MA-primed locomotor activity. In a second set of experiments we
      characterized the individual contributions of ACh originating in the LDT or
      pedunculopontine tegmental nucleus (PPT) to MA-induced levels of ACh and DA by
      administering intra-LDT or PPT OXO and performing in vivo microdialysis in the
      VTA and NAc. Intra-LDT OXO dose-dependently attenuated the MA-induced increase in
      ACh within the VTA but had no effect on DA in NAc. Intra-PPT OXO had no effect on
      ACh or DA levels within the VTA or NAc, respectively. We conclude that LDT, but
      not PPT, ACh is important in locomotor behavior and the cholinergic, but not
      dopaminergic, response to systemic MA.

PMID- 21945299
TI  - Different pathophysiology underlying animal models of fibromyalgia and
      neuropathic pain: comparison of reserpine-induced myalgia and chronic
      constriction injury rats.
AB  - The reserpine-induced myalgia (RIM) rat manifests fibromyalgia-like chronic pain
      symptoms. The present study explored the pathophysiology underlying the pain
      symptoms in the RIM rat and the chronic constriction injury (CCI) rat, an animal
      model of neuropathic pain as a reference. Nerve tissue samples were collected
      from the nociception-tested animals for pathological examinations. Additionally,
      the therapeutic efficacy of a sodium channel blocker mexiletine was assessed in
      both rats. A slight vacuolization in the substantia nigra (SN) occurred in some
      of the RIM rats without any other histopathological changes in the brain or
      peripheral neurons. All the RIM rats, with or without vacuolization, showed
      hypersensitivity to tactile, muscle pressure, and cold stimuli. In the CCI rat,
      neurodegenerative changes were apparent in the sciatic nerve and the spinal cord
      only. CCI rats displayed muscle hyperalgesia in addition to tactile and cold
      allodynia. Pharmacotherapy with mexiletine did not attenuate the pain in the RIM
      rat, although it was effective in the CCI rat. Taken together, it is not likely
      that pain symptoms in RIM rats are caused by degenerative changes at the level of
      primary afferents and spinal cord, as is the case for CCI rats. The significance
      of the vacuolization in the SN is less clear at present because of the minor
      extent of the change and the lack of correlation with nociceptive sensitivity.
      The pain symptoms in RIM rats could be associated with dysfunction of biogenic
      amines-mediated CNS pain control even without apparent pathologies in the nervous
      system.

PMID- 21945301
TI  - Epidemiological indication for a role of sheep in the emergence of variant
      Creutzfeldt-Jakob disease.

PMID- 21945302
TI  - Expression of aquaporin-1, -2 and -4 in mice with a spontaneous mutation leading
      to hydronephrosis.
AB  - This study investigates the expression of aquaporin-1, -2 and -4 in mice with a
      spontaneously-arising mutation that leads to hydronephrosis (ICR/Mlac-hydro
      mice). The mutant mice developed bilateral non-obstructive hydronephrosis without
      evidence of interstitial fibrosis or glomerulosclerosis. The mice had no
      abnormality in blood urea nitrogen or creatinine concentrations or in urine
      specific gravity. Despite the severity of the renal damage the mice grew and
      reproduced normally. Kidneys from the mutant mice had reduced expression of all
      three aquaporins compared with wild type mice. The reduction in aquaporin was
      proportional to the degree of hydronephrosis, but this change did not appear to
      be associated with disturbance of urinary function.

PMID- 21945300
TI  - Environmental enrichment reduces attribution of incentive salience to a food
      associated stimulus.
AB  - Animals reared in an enriched environment are less vulnerable to abuse-like
      behavior and exhibit less persistent drug seeking, perhaps due to a decrease in
      the incentive value of stimuli associated with reward. The present study
      investigated the effects of environmental enrichment on Pavlovian conditioned
      approach (PCA) performance, a measure of incentive salience attribution. Rats
      were first reared from postnatal day 21 to postnatal day 51 in either an enriched
      environment with large cages, social cohorts and novel objects, or in an isolated
      environment with small, hanging cages, no social cohorts and no novel objects.
      Rats were then trained on a PCA task for 5 consecutive days, where a retractable
      lever was predictive of a food reward. Isolated rats predominantly exhibited sign
      tracking responses directed toward the reward-predicted lever (indicative of
      incentive salience attribution), while enriched rats predominantly exhibited goal
      tracking responses directed toward the location of food delivery. Both groups
      learned their respective response type at equal rates. The results indicate that
      environmental enrichment reduces the readiness to attribute incentive value to
      reward-associated cues, which may explain the enrichment-induced protection
      against addiction-like behaviors.

PMID- 21945303
TI  - Monitoring compliance to therapy during addiction treatments by means of hair
      analysis for drugs and drug metabolites using capillary zone electrophoresis
      coupled to time-of-flight mass spectrometry.
AB  - Capillary electrophoresis coupled to time-of-flight mass spectrometry was used in
      the present work for the determination of therapeutic and abused drugs and their
      metabolites in the hair of subjects undergoing addiction treatments, in order to
      monitor their compliance to therapy. For this purpose a rapid, qualitative drug
      screening method was adopted based on capillary electrophoresis hyphenated with
      time-of-flight mass spectrometry, which had earlier been developed and validated
      for the forensic-toxicological analysis of hair, limitedly to illicit/abused
      drugs [1]. Sampling of hair was carried out in order to refer to a time window of
      about two months from the date of sampling (i.e. 2cm ca. from cortex). A single
      extraction procedure was applied, allowing the determination in the hair matrix
      of "drugs of abuse" referred to the past abuses, and therapeutic drugs prescribed
      in the detoxification program as well as their metabolites. Analyte
      identification was based on accurate mass measurements and comparison of isotope
      patterns, providing the most likely matching between accurate mass value and
      elemental formula. Small molecules (<500Da) of forensic and toxicological
      interest could be identified unambiguously using mass spectrometric conditions
      tailored to meet a mass accuracy <=5ppm. In the present study, the proposed
      approach proved suitable for the rapid broad spectrum screening of hair samples,
      although needing further confirmation of results by using fragmentation mass
      spectrometry.

PMID- 21945304
TI  - Endogenous ethanol production in patients with diabetes mellitus as a medicolegal
      problem.
AB  - Ethanol which is not ingested but is produced within the body through metabolic
      processes is known as "endogenous ethanol" (EnEth). The aim of this study was to
      determine whether there is a significant increase in the blood value of EnEth
      (BAC) in patients with diabetes mellitus and whether BAC correlates with
      increased glucose blood levels. In our study the BAC in the group of patients
      with diabetes mellitus (n=130) was significantly higher (mean value 2.65mg/L)
      than in the control group (mean value 0.40mg/L) when blood samples were analyzed
      by headspace gas chromatography method (HS-GC). The BAC levels obtained by semi
      quantitative Widmark's method (n=60) were higher, and mean value in the patient
      group was 27.28mg/L. There was no correlation between the glucose blood levels
      and BAC, i.e. the auto-production of ethanol does not depend on blood glucose
      values. The mean value of ethanol in urine in patients with diabetes mellitus was
      6.13mg/L measured by HS-GC method and 54.27mg/L when measured using Widmark's
      method. Even though the BAC in patients with diabetes mellitus was statistically
      significantly higher (p<0.01) in comparison to the control group, these amounts
      of EnEth do not increase greatly enough to affect legal proceedings, especially
      considering the fact that EnEth is measured in mg/mL. Our experimental results as
      well as data reported in the literature suggest that the cut-off level for the
      EnEth in blood should be set at BAC<0.1mg/mL for the semi-quantitative method,
      i.e. the values that appear at the second decimal place cannot be with certainty
      claimed to arise form the exogenous ethanol. For the HS-GS method cut-off level
      should be set at BAC<0.01mg/mL for the analytical parameters that were used in
      our experiments.

PMID- 21945305
TI  - N-acetylcysteine normalizes neurochemical changes in the glutathione-deficient
      schizophrenia mouse model during development.
AB  - BACKGROUND: Glutathione (GSH) is the major cellular redox-regulator and
      antioxidant. Redox-imbalance due to genetically impaired GSH synthesis is among
      the risk factors for schizophrenia. Here we used a mouse model with chronic GSH
      deficit induced by knockout (KO) of the key GSH-synthesizing enzyme, glutamate
      cysteine ligase modulatory subunit (GCLM). METHODS: With high-resolution magnetic
      resonance spectroscopy at 14.1 T, we determined the neurochemical profile of GCLM
      KO, heterozygous, and wild-type mice in anterior cortex throughout development in
      a longitudinal study design. RESULTS: Chronic GSH deficit was accompanied by an
      elevation of glutamine (Gln), glutamate (Glu), Gln/Glu, N-acetylaspartate, myo
      Inositol, lactate, and alanine. Changes were predominantly present at prepubertal
      ages (postnatal days 20 and 30). Treatment with N-acetylcysteine from gestation
      on normalized most neurochemical alterations to wild-type level. CONCLUSIONS:
      Changes observed in GCLM-KO anterior cortex, notably the increase in Gln, Glu,
      and Gln/Glu, were similar to those reported in early schizophrenia, emphasizing
      the link between redox imbalance and the disease and validating the model. The
      data also highlight the prepubertal period as a sensitive time for redox-related
      neurochemical changes and demonstrate beneficial effects of early N
      acetylcysteine treatment. Moreover, the data demonstrate the translational value
      of magnetic resonance spectroscopy to study brain disease in preclinical models.

PMID- 21945306
TI  - Neurobiological elements of cognitive dysfunction in down syndrome: exploring the
      role of APP.
AB  - Down syndrome (DS) is the most common cause of cognitive dysfunction in children.
      Additionally, most adults with DS will eventually show both clinical and
      neuropathologic hallmarks of Alzheimer's disease (AD). The hippocampal formation
      constitutes the primary target for degeneration in both AD and DS. Over the past
      few years, we have studied the molecular mechanisms behind degeneration of this
      region and its major inputs in mouse models of DS. Our investigation has
      suggested that the loss of hippocampal inputs, particularly cholinergic and
      noradrenergic terminals, leads to de-afferentation of this region in the Ts65Dn
      mouse model of DS. Interestingly, we were able to link the overexpression of
      amyloid precursor protein (App) gene to degeneration of cholinergic and
      noradrenergic neurons in DS mouse models. We examined the underlying mechanisms
      of degeneration of multiple systems with extensive projections to the hippocampus
      in DS and its mouse models and the role of App overexpression in
      neurodegeneration. Understanding mechanisms behind hippocampal dysfunction has
      helped us to test several therapeutic strategies successfully in mouse models of
      DS. Here we review these strategies and mechanisms and discuss ways to translate
      our findings into possible interventions in humans.

PMID- 21945307
TI  - Three-dimensional classification of radical hysterectomy: new saddle for an old
      horse.

PMID- 21945308
TI  - Costunolide induces apoptosis in platinum-resistant human ovarian cancer cells by
      generating reactive oxygen species.
AB  - OBJECTIVE: The acquired resistance to platinum-based drugs has become an obstacle
      in the management of ovarian cancer. We investigated the apoptosis-inducing
      effect of costunolide, a natural sesquiterpene lactone, in platinum-resistant
      human ovarian cancer cells, along with the molecular mechanism of action.
      METHODS: Costunolide and cisplatin were examined in platinum-resistant human
      ovarian cancer cells. MTT assay for cell viability, PI staining for cell cycle
      profiling, and Annexin V assay for apoptosis analysis. ROS production and protein
      expression was assessed by H(2)DCFDA staining and Western blotting, respectively.
      Combination effect was determined using the Combination Index (CI) method.
      RESULTS: It was found that costunolide is more potent than cisplatin in
      inhibiting cell growth in three platinum-resistant ovarian cancer cell lines
      (MPSC1(PT), A2780(PT), and SKOV3(PT)). Costunolide induced apoptosis of platinum
      resistant cells in a time- and dose-dependent manner and suppressed tumor growth
      in SKOV3(PT)-bearing mouse model. In addition, costunolide triggered the
      activation of caspase-3, -8, and -9. Pretreatment with caspase inhibitors
      neutralized the pro-apoptotic activity of costunolide. We further demonstrated
      that costunolide induced a significant increase in intracellular reactive oxygen
      species (ROS). Additionally, the antioxidant N-acetyl-L-cysteine (NAC)
      significantly attenuated the costunolide-induced production of ROS, activation of
      caspases, down-regulation of Bcl-2, and apoptosis in platinum-resistant ovarian
      cancer cells. Moreover, costunolide synergized with cisplatin to induce cell
      death in platinum-resistant ovarian cancer cells. CONCLUSIONS: Taken together,
      these data suggest that costunolide, alone or in combination with cisplatin, may
      be of therapeutic potential in platinum-resistant ovarian cancer.

PMID- 21945309
TI  - Neoadjuvant chemotherapy in the Medicare cohort with advanced ovarian cancer.
AB  - OBJECTIVE: The value of neoadjuvant chemotherapy (NAC) for the treatment of
      advanced ovarian cancer has yet to be determined. While NAC may facilitate and
      simplify complete cytoreduction and reduce the risk of surgery, the delay of
      surgery related to NAC needs to be balanced against any potential benefit.
      METHODS: Surveillance, Epidemiology and End-Results (SEER) data linked to
      Medicare claims were used to identify 6844 women with treated stage III/IV
      epithelial ovarian cancer (1995-2005). Patients were classified by primary
      treatment (surgery (PDS) or chemotherapy), and the primary chemotherapy group was
      characterized as having NAC or palliative chemotherapy (PC) based on whether
      there was documentation that surgery was recommended. We compared surgical
      complications and survival between the groups. RESULTS: 4827 (71%) of women were
      treated with PDS, 958 received NAC (14%) and 1059 (15%) had PC. Only 577 (60%) of
      women with NAC underwent surgery and they had fewer ostomies (8.5% vs. 19.2%,
      p<0.001) and fewer infections, gastrointestinal and pulmonary complications than
      PDS (all p<0.01). Comparing NAC to PDS there was a 16% increase in the risk of
      death at 2years (RR 1.16, 95%CI 1.01-1.34) for women with stage III disease and a
      15% reduction in the risk for women with stage IV disease (RR 0.85, 95%CI 0.73
      0.99). CONCLUSIONS: NAC followed by surgery was associated with fewer surgical
      complications than PDS. The direction and magnitude of the difference in survival
      between women receiving NAC and those receiving PDS differed according to the
      stage of disease and follow up time.

PMID- 21945310
TI  - Health-related quality of life outcomes of docetaxel/carboplatin combination
      therapy vs. sequential therapy with docetaxel then carboplatin in patients with
      relapsed, platinum-sensitive ovarian cancer: results from a randomized clinical
      trial.
AB  - OBJECTIVES: A phase II clinical trial compared docetaxel in combination with
      carboplatin to sequential single agent docetaxel followed by carboplatin for
      treatment of recurrent platinum-sensitive ovarian, peritoneal, or tubal cancer.
      This manuscript reports prospectively collected health-related quality of life
      (HRQL). METHODS: Participants were randomized to either weekly docetaxel 30
      mg/m(2)/days 1 and 8 and carboplatin AUC 6/day 1 every 3 weeks (cDC) or docetaxel
      30 mg/m(2)/days 1 and 8, repeated every 3 weeks for 6 cycles followed by
      carboplatin AUC 6/day 1 every 3 weeks for 6 cycles or until disease progression
      (sDC). The primary HRQL endpoint was the trial outcome index (TOI) score of the
      Functional Assessment of Cancer Therapy-Ovarian (FACT-O) instrument, and was
      assessed as an intent-to-treat analysis. The secondary HRQL endpoints included
      the FACT-O total score, the FACT-General, and several domain scores of the FACT-O
      instrument (physical well-being (PWB), social/family well-being (SWB), emotional
      well-being (EWB), functional well-being (FWB), and the ovarian cancer specific
      (OCS) module). The FACT-O was administered at randomization, prior to each of 6
      cycles of treatment, and at study endpoint. RESULTS: One hundred forty-eight
      participants were randomized to each group. Sequential docetaxel followed by
      carboplatin (sDC) was associated with significant improvements in the FACT-O TOI
      (p=0.013), FACT-O total score (p=0.033), and OCS (p=0.029) compared to the
      combination docetaxel and carboplatin group (cDC). CONCLUSIONS: Sequential single
      agent docetaxel followed by carboplatin is associated with improved HRQL when
      compared to cDC. The improved progression-free survival observed with cDC should
      be weighed against lower quality of life during treatment.

PMID- 21945311
TI  - Prevalence of malnutrition and risk of under-nutrition in hospitalized children.
AB  - BACKGROUND & AIMS: Malnutrition can increase morbidity or mortality and
      hospitalization may further increase the risk of nutritional deterioration. This
      study aimed to assess the prevalence of malnutrition and nutritional risk in
      hospitalized children and to identify any associated factors. METHODS:
      Nutritional status and risk was defined in 157 hospitalized children using
      anthropometry and a nutritional risk score (NRS). RESULTS: The frequency of
      wasted, stunted, overweight and obese children was 4.5%, 8.9%, 15.1% and 10.4%
      respectively. Half (52.6%) of the undernourished children were aged less than 2
      years of age. Forty-eight percent of the overweight or obese children were aged
      between 10 and 18 years of age. Based on their NRSs, 47.8% of the children
      assessed were at high risk of nutritional deterioration whereas 28.7% were at no
      nutritional risk. Children with higher nutritional risk scores had lower weight
      for age (p=0.02), lower BMI percentiles (p=0.001) and longer hospitalization
      (p=0.001) than children at no risk. CONCLUSIONS: One quarter of these
      hospitalized children were overweight or obese. NRSs identified a group of
      children at increased risk of nutritional deterioration who subsequently had
      longer hospital stays. Use of NRSs at admission can identify children requiring
      focused nutritional assessment.

PMID- 21945312
TI  - Immunomodulatory therapy in recurrent acute necrotizing encephalopathy ANE1: is
      it useful?
AB  - Acute Necrotizing Encephalopathy (ANE) is a rare disorder characterized by fever,
      seizures and rapid progression to coma after the onset of a viral infection. Most
      cases are sporadic, however the observation of multiple cases in the same family
      with recurrent episodes of ANE led to the identification of a genetic form of the
      disorder, called ANE1, and to the discover of the causative mutation in RANBP2
      gene. We report the first Italian child with ANE1 carrying the common c.1880C>T
      mutation in the RANBP2 gene, who presented three episodes of acute encephalopathy
      in the first two years of life. The child showed a less severe clinical and
      neuroradiological course with respect to the previously reported patients. During
      the acute encephalopathy episodes he was treated with steroids and
      immunoglobulin. A very low steroid maintenance therapy was administered after the
      second episode until the onset of the third. Thirty days after the last episode
      he started monthly intravenous immunoglobulin that might be used for prevention
      of viral infections. At the moment he is still continuing a low steroid
      maintenance therapy and monthly IVIG. We could hypothesize that the less severe
      clinical presentation of the third episode might be correlated to the steroid
      treatment or that the patient grew older. Despite there is no evidence to support
      that ANE1 is an immune-mediated disease, immunomodulatory therapy might be
      considered in the management of ANE1 cases especially in early childhood, in
      which a fatal course has been frequently reported. Further studies will be
      necessary to define the clinical, immunological and genetic aspects, as well as
      the outcome of immunomodulatory therapy in patients with ANE1.

PMID- 21945313
TI  - Survival of patients with bilateral versus unilateral breast cancer and impact of
      guideline adherent adjuvant treatment: a multi-centre cohort study of 5292
      patients.
AB  - This retrospective multi-centre study is focussed on recurrence free and overall
      survival of bilateral breast cancer (BBC) versus unilateral breast cancer (UBC).
      The impact of BBC on survival is stratified to guideline adherence, according to
      the German national S3-guideline. Another aim of the study is to identify the
      influence of various guideline violations in adjuvant treatment on survival of
      BBC patients. 229 (4.3%) patients had BBC and 5063 (95.7%) had UBC. There is a
      significant association between BBC/UBC and recurrence free (RFS: p < 0.001) and
      overall survival (OAS: p = 0.003). Only 15.7% of patients with BBC are treated
      100% guideline adherent (index- + contralateral tumour). 31.0% (30.5%) were
      guideline adherent with respect to the index (contralateral) tumour. The outcome
      decreases significantly with the number of guideline violations. There was no
      significant difference in RFS and OAS between BBC and UBC after adjusting for
      tumour size, nodal status, grading and if guideline adherent treatment was
      applied. CONCLUSION: 1. Patients with BBC have primarily a worse prognosis in
      terms of RFS and OAS than patients with primarily UBC. 2. There is a strong
      association between guideline adherence and RFS/OAS of patients with BBC or UBC.
      The outcome decreases with the number of guideline violations. 3. If guideline
      adherent treatment was applied (for both tumours in case of BBC) there was no
      significant difference in RFS and OAS between BBC and UBC after adjusting for
      tumour size, nodal status, grading.

PMID- 21945314
TI  - MiR-143 enhances adipogenic differentiation of 3T3-L1 cells through targeting the
      coding region of mouse pleiotrophin.
AB  - Adipogenic differentiation of preadipocytes is a complex process regulated by
      various factors including miRNAs and cytokines. MiR-143 is a well known miRNA
      that enhances adipogenesis. Pleiotrophin (PTN), a heparin-binding growth factor,
      plays a negative role in adipogenesis. In this investigation, we demonstrate that
      PTN is a target gene of miR-143 during adipogenic differentiation in 3T3-L1
      preadipocytes. MiR-143 down regulates PTN expression through interaction with a
      target site of miR-143 in the coding region of mouse PTN. The rare codons
      upstream of the target site regulate miR143-induced translational knockdown of
      PTN, which provides more insight into the mechanism of adipogenic
      differentiation.

PMID- 21945315
TI  - The catalytic domain of MMP-1 studied through tagged lanthanides.
AB  - Pseudocontact shifts (pcs) and paramagnetic residual dipolar couplings (rdc)
      provide structural information that can be used to assess the adequacy of a
      crystallographic structure to represent the solution structure of a protein. This
      can be done by attaching a lanthanide binding tag to the protein. There are cases
      in which only local rearrangements are sufficient to match the NMR data and cases
      where significant secondary structure or domain rearrangements from the solid
      state to the solution state are needed. We show that the two cases are easily
      distinguishable. Whereas the use of solution restraints in the latter case is
      described in the literature, here we deal with how to obtain a better model of
      the solution structure in a case (the catalytic domain of the matrix
      metalloproteinase MMP-1) of the former class.

PMID- 21945316
TI  - Time-specific regulation of airway clearance by the Drosophila J-domain
      transmembrane protein Wurst.
AB  - At the end of embryogenesis, Drosophila and mammalian airways convert from liquid
      filled to air-filled tubes. This process is regulated by Clathrin-mediated
      endocytosis. However, these molecular mechanisms are poorly understood. In
      Drosophila, the DnaJ transmembrane protein Wurst interacts with Clathrin and
      Hsc70 to mediate early steps of endocytosis. Wurst is expressed in epithelial
      tissues from early stages onwards. Here we show time- and tissue-specific
      requirement of Wurst in airway liquid-clearance and air-filling. RNAi experiments
      demonstrate that Wurst activity is specifically required at the final stage 17 of
      embryogenesis. Furthermore, we show that the apical membrane organizer Crumbs
      regulates Wurst-mediated airway liquid-air-transition.

PMID- 21945317
TI  - siRNA-mediated knockdown of aryl hydrocarbon receptor nuclear translocator 2
      affects hypoxia-inducible factor-1 regulatory signaling and metabolism in human
      breast cancer cells.
AB  - Recent human studies found that the mRNA expression level of aryl-hydrocarbon
      receptor nuclear translocator 2 (ARNT2) was positively associated with the
      prognosis of breast cancer. In this study, we used small interfering RNA
      techniques to knockdown ARNT2 expression in MCF7 human breast cancer cells, and
      found that an almost 40% downregulation of ARNT2 mRNA expression increased the
      expression of sensitive to apoptosis gene (3.36-fold), and decreased the
      expression of von Hippel-Lindau (0.27-fold) and matrix metalloproteinase-1 (0.35
      fold). The metabolite analysis revealed the contents of glucose, glycine,
      betaine, phosphocholine, pyruvate and lactate involved in the hypoxia-inducible
      factor (HIF)-1-dependent glycolytic pathway were significantly lower in cells
      treated with siARNT2. Our results suggested that ARNT2 might play an important
      role in the modulation of HIF-1-regulated signaling and metabolism.

PMID- 21945318
TI  - The beta-isoform of neuronal nitric oxide synthase (nNOS) lacking the PDZ domain
      is localized at the sarcolemma.
AB  - In skeletal muscles, the expression of neuronal NO synthase (nNOS) isoforms is
      uncharacterized at the protein level. We therefore conducted epitope mapping with
      anti-peptide-antibodies. Antibodies specific for the nNOS N-terminus recognized
      the 160-kDa alpha-isoform. In contrast, antibodies against the middle portion or
      the C-terminus of nNOS bound additionally to the truncated 140-kDa beta-isoform
      which lacks the PDZ-domain present in the alpha-isoform. All nNOS
      immunohistochemical reactivity was confined to the sarcolemma. Consistently,
      immunoblotting disclosed both nNOS-isoforms to be co-enriched in the membrane
      associated fractions. The beta-isoform was co-immunoprecipitated with alpha
      isoform antibodies in muscle extracts indicating an association of both nNOS
      isoforms to direct the beta-variant to the sarcolemma.

PMID- 21945319
TI  - Respiratory chain complex I, a main regulatory target of the cAMP/PKA pathway is
      defective in different human diseases.
AB  - In mammals, complex I (NADH-ubiquinone oxidoreductase) of the mitochondrial
      respiratory chain has 31 supernumerary subunits in addition to the 14 conserved
      from prokaryotes to humans. Multiplicity of structural protein components, as
      well as of biogenesis factors, makes complex I a sensible pace-maker of
      mitochondrial respiration. The work reviewed here shows that the cAMP/PKA pathway
      regulates the biogenesis, assembly and catalytic activity of complex I and
      mitochondrial oxygen superoxide production. The structural, functional and
      regulatory complexity of complex I, renders it particularly vulnerable to genetic
      and sporadic pathological factors. Complex I dysfunction has, indeed, been found,
      to be associated with several human diseases. Knowledge of the pathogenetic
      mechanisms of these diseases can help to develop new therapeutic strategies.

PMID- 21945320
TI  - Biochemical engineering of the N-acyl side chain of sialic acids alters the
      kinetics of a glycosylated potassium channel Kv3.1.
AB  - The sialic acid of complex N-glycans can be biochemically engineered by
      substituting the physiological precursor N-acetylmannosamine with non-natural N
      acylmannosamines. The Kv3.1 glycoprotein, a neuronal voltage-gated potassium
      channel, contains sialic acid. Western blots of the Kv3.1 glycoprotein isolated
      from transfected B35 neuroblastoma cells incubated with N-acylmannosamines
      verified sialylated N-glycans attached to the Kv3.1 glycoprotein. Outward ionic
      currents of Kv3.1 transfected B35 cells treated with N-pentanoylmannosamine or N
      propanoylmannosamine had slower activation and inactivation rates than those of
      untreated cells. Therefore, the N-acyl side chain of sialic acid is intimately
      connected with the activation and inactivation rates of this glycosylated
      potassium channel.

PMID- 21945321
TI  - LMNA mutations induce a non-inflammatory fibrosis and a brown fat-like dystrophy
      of enlarged cervical adipose tissue.
AB  - Some LMNA mutations responsible for insulin-resistant lipodystrophic syndromes
      are associated with peripheral subcutaneous lipoatrophy and faciocervical fat
      accumulation. Their pathophysiologic characteristics are unknown. We compared
      histologic, immunohistologic, ultrastructural, and protein expression features of
      enlarged cervical subcutaneous adipose tissue (scAT) obtained during plastic
      surgery from four patients with LMNA p.R482W, p.R439C, or p.H506D mutations
      versus cervical fat from eight control subjects, buffalo humps from five patients
      with HIV infection treated or not with protease inhibitors, and dorsocervical
      lipomas from two patients with mitochondrial DNA mutations. LMNA-mutated cervical
      scAT and HIV-related buffalo humps were dystrophic, with an increased percentage
      of small adipocytes, increased fibrosis without inflammatory features, and
      decreased number of blood vessels, as compared with control samples. Samples from
      patients with LMNA mutations or protease inhibitor-based therapy demonstrated
      accumulation of prelamin A, altered expression of adipogenic proteins and brown
      fat-like features, with an increased number of mitochondria and overexpression of
      uncoupling protein 1 (UCP1). These features were absent in samples from control
      subjects and from patients with HIV not treated with protease inhibitors.
      Mitochondrial DNA-mutated cervical lipomas demonstrated inflammatory fibrosis
      with distinct mitochondrial abnormalities but neither UCP1 expression nor
      prelamin A accumulation. In conclusion, Enlarged cervical scAT from patients with
      lipodystrophy demonstrated small adipocytes, fibrosis, and decreased vessel
      numbers. However, only cervical fat from patients with LMNA mutations or who had
      received protease inhibitor therapy accumulated prelamin A and exhibited similar
      remodeling toward a brown-like phenotype with UCP1 overexpression and
      mitochondrial alterations.

PMID- 21945323
TI  - miR-375 is down-regulated in squamous cervical cancer and inhibits cell migration
      and invasion via targeting transcription factor SP1.
AB  - Pelvic lymph node metastases are regarded as the most important risk factor and a
      predictor of poor prognosis for patients with cervical cancer. Exploration of
      metastasis-related molecules is helpful toward improving the prognosis in
      cervical cancer. To identify the role of miR-375 in metastasis and progression of
      cervical cancer, we examined the expression of miR-375 in 170 cervical cancer
      tissues and 68 normal cervical tissues, using stem-loop quantitative PCR, and
      found that the expression of miR-375 in cervical cancer tissues was significantly
      decreased by 4.45-fold, compared with 68 normal tissues. A significant
      correlation existed between miR-375 expression and clinicopathologic parameters,
      including lymph node metastasis of cervical cancer. Overexpressed miR-375
      suppressed cell proliferation, blocked G1-to-S cell-cycle transition, and
      inhibited cell migration and invasion in human cervical SiHa and CaSki cells.
      SP1, a potential target gene of miR-375, was inversely correlated with miR-375
      expression in cervical cancer tissues. Moreover, SP1 was negatively regulated by
      miR-375, and knockdown of SP1 by siRNA inhibited cell malignant behaviors. Thus,
      our findings suggest that down-regulated miR-375 promotes cell malignant
      behaviors via the target gene SP1 and may consequently contribute to the
      progression of cervical cancer.

PMID- 21945322
TI  - Inflammation-induced endothelial-to-mesenchymal transition: a novel mechanism of
      intestinal fibrosis.
AB  - In addition to mesenchymal cells, endothelial cells may contribute to fibrosis
      through the process of endothelial-to-mesenchymal transition (EndoMT). We
      investigated whether human intestinal microvascular endothelial cells (HIMEC)
      undergo EndoMT and contribute to fibrosis in human and experimental inflammatory
      bowel disease (IBD). HIMEC were exposed to TGF-beta1, IL-1beta, and TNF-alpha or
      supernatants of lamina propria mononuclear cells (LPMC) and evaluated for
      morphological, phenotypic, and functional changes compatible with EndoMT. Genomic
      analysis was used to identify transcription factors involved in the
      transformation process. Evidence of in situ and in vivo EndoMT was sought in
      inflamed human and murine intestine. The combination of TGF-beta1, IL-1beta and
      TNF-alpha, or activated LPMC supernatants induced morphological and phenotypic
      changes consistent with EndoMT with a dominant effect by IL-1. These changes
      persisted after removal of the inducing agents and were accompanied by functional
      loss of acetylated LDL-uptake and migratory capacity, and acquisition of de novo
      collagen synthesis capacity. Sp1 appeared to be the main transcriptional
      regulator of EndoMT. EndoMT was detected in microvessels of inflammatory bowel
      disease (IBD) mucosa and experimental colonic fibrosis of Tie2-green fluorescent
      protein (GFP) reporter-expressing mice. In conclusion, chronic inflammation
      induces transdifferentiation of intestinal mucosal microvascular cells into
      mesenchymal cells, suggesting that the intestinal microvasculature contributes to
      IBD-associated fibrosis through the novel process of EndoMT.

PMID- 21945325
TI  - Effects of abamectin exposure on male fertility in rats: potential role of
      oxidative stress-mediated poly(ADP-ribose) polymerase (PARP) activation.
AB  - Despite the known adverse effects of abamectin pesticide, little is known about
      its action on male fertility. To explore the effects of exposure to abamectin on
      male fertility and its mechanism, low (1mg/kg/day) and high dose (4 mg/kg/day)
      abamectin were applied to male rats by oral gavage for 1week and for 6weeks.
      Weight of testes, serum reproductive hormone levels, sperm dynamics and
      histopathology of testes were used to evaluate the reproductive efficiency of
      abamectin-exposed rats. Abamectin level was determined at high concentrations in
      plasma and testicular tissues of male rats exposed to this pesticide. The testes
      weights of animals and serum testosterone concentrations did not show any
      significant changes after abamectin exposure. Abamectin administration was
      associated with decreased sperm count and motility and increased seminiferous
      tubule damage. In addition, significant elevations in the 4-hydroxy-2-nonenal (4
      HNE)-modified proteins and poly(ADP-ribose) (PAR) expression, as markers for
      oxidative stress and poly(ADP-ribose) polymerase (PARP) activation, were observed
      in testes of rats exposed to abamectin. These results showed that abamectin
      exposure induces testicular damage and affects sperm dynamics. Oxidative stress
      mediated PARP activation might be one of the possible mechanism(s) underlying
      testicular damage induced by abamectin.

PMID- 21945324
TI  - VEGFR-1 mediates endothelial differentiation and formation of blood vessels in a
      murine model of infantile hemangioma.
AB  - Vascular endothelial growth factor receptor-1 (VEGFR-1) is a member of the VEGFR
      family, and binds to VEGF-A, VEGF-B, and placental growth factor. VEGFR-1
      contributes to tumor growth and metastasis, but its role in the pathological
      formation of blood vessels is still poorly understood. Herein, we used infantile
      hemangioma (IH), the most common tumor of infancy, as a means to study VEGFR-1
      activation in pathological vasculogenesis. IH arises from stem cells (HemSCs)
      that can form the three most prominent cell types in the tumor: endothelial
      cells, pericytes, and adipocytes. HemSCs can recapitulate the IH life cycle when
      injected in immuncompromised mice, and are targeted by corticosteroids, the
      traditional treatment for IH. We report here that VEGF-A or VEGF-B induces VEGFR
      1-mediated ERK1/2 phosphorylation in HemSCs and promotes differentiation of
      HemSCs to endothelial cells. Studies of VEGFR-2 phosphorylation status and down
      regulation of neuropilin-1 in the HemSCs demonstrate that VEGFR-2 and NRP1 are
      not needed for VEGF-A- or VEGF-B-induced ERK1/2 activation. U0216-mediated
      blockade of ERK1/2 phosphorylation or shRNA-mediated suppression of VEGFR-1
      prevents HemSC-to-EC differentiation. Furthermore, the down-regulation of VEGFR-1
      in the HemSCs results in decreased formation of blood vessels in vivo and reduced
      ERK1/2 activation. Thus, our study reveals a critical role for VEGFR-1 in the
      HemSC-to-EC differentiation that underpins pathological vasculogenesis in IH.

PMID- 21945326
TI  - CYP-eicosanoids--a new link between omega-3 fatty acids and cardiac disease?
AB  - Fish oil omega-3 fatty acids such as eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA) protect against arrhythmia and sudden cardiac death by
      largely unknown mechanisms. Recent in vitro and in vivo studies demonstrate that
      arachidonic acid (AA) metabolizing cytochrome P450-(CYP) enzymes accept EPA and
      DHA as efficient alternative substrates. Dietary EPA/DHA supplementation causes a
      profound shift of the cardiac CYP-eicosanoid profile from AA- to EPA- and DHA
      derived epoxy- and hydroxy-metabolites. CYP2J2 and other CYP epoxygenases
      preferentially epoxidize the omega-3 double bond of EPA and DHA. The
      corresponding metabolites, 17,18-epoxy-EPA and 19,20-epoxy-DHA, dominate the CYP
      eicosanoid profile of the rat heart after EPA/DHA supplementation. The (omega-3)
      epoxyeicosanoids show highly potent antiarrhythmic properties in neonatal
      cardiomyocytes, suggesting that these metabolites may specifically contribute to
      the cardioprotective effects of omega-3 fatty acids. This hypothesis is discussed
      in the context of recent findings that revealed CYP-eicosanoid mediated
      mechanisms in cardiac ischemia-reperfusion injury and maladaptive cardiac
      hypertrophy.

PMID- 21945328
TI  - Virulence of an exotoxin A-deficient strain of Pseudomonas aeruginosa toward the
      silkworm, Bombyx mori.
AB  - We studied the contribution of exotoxin A to the virulence of Pseudomonas
      aeruginosa against the silkworm, Bombyx mori. First, an exotoxin A-deficient
      mutant strain (PAO1toxA) was created, and its virulence compared with that of the
      parental PAO1 strain. In a short-term mortality assay, the mutant harboring
      pBBR1MCS2 did not kill B. mori until 120 h after inoculation and complementation
      of the corresponding gene in trans restored the strain's virulence. Next, to
      ascertain whether or not it lost all virulence, PAO1toxA (pBBR1MCS2, pGFP) was
      used in a long-term mortality assay. B. mori inoculated with the mutant strain
      did not die until early in the 5th instar (240 h after inoculation). However, 50%
      of the inoculated B. mori died late in the 5th instar or in the early pupal stage
      (408 h after inoculation). All had died by the pupal stage (600 h after
      inoculation). The mutant strain was isolated from dead larvae and cocoons. The
      bacterial population of PAO1toxA in hemolymph reached 4.77 * 10(7) cfu/ml. These
      results indicated that exotoxin A acts as a virulence factor in B. mori and that
      other virulence factor(s) are involved during the late stages of infection.

PMID- 21945327
TI  - Asymptomatic infection of visceral leishmaniasis in hyperendemic areas of
      Vaishali district, Bihar, India: a challenge to kala-azar elimination programmes.
AB  - A cohort of 91 asymptomatic individuals with visceral leishmaniasis (VL) were
      identified during base line screening using recombinant 39-aminoacid antigen (rk
      39) and polymerase chain reaction (PCR) conducted from December 2005 to June 2006
      involving 997 individuals of two highly endemic villages of Vaishali district,
      Bihar. The point prevalence of asymptomatic infection was 98 per 1000 persons at
      baseline. There was no statistically significant difference between rk-39 and PCR
      positivity rate (P>0.05), even though PCR positivity alone was found
      significantly higher (4.2%) than rk-39 positivity alone (2.6%). The monthly
      follow-up of the asymptomatic cohort revealed a disease conversion rate of 23.1
      per 100 persons within a year. There was a statistically significant difference
      in conversion of disease when individuals were positive by both tests as compared
      to single tests by rk-39 and PCR (P<0.01). Disease conversion rate in the
      subjects residing in households with a history of VL (62%, 13/21) was higher than
      those residing in the households without a history of VL (38%, 8/21). Most of the
      identified asymptomatic individuals were from low socio-economic strata similar
      to that of VL cases in general. Apart from rk-39, PCR may be considered for
      screening of asymptomatic Leishmania donovani infection in large-scale
      epidemiological studies. Screening of asymptomatic cases and their close follow
      up to ascertain early detection and treatment of VL may be considered in addition
      to the existing VL control strategies.

PMID- 21945329
TI  - Areas of left perisylvian cortex mediate auditory-verbal short-term memory.
AB  - A contentious issue in memory research is whether verbal short-term memory (STM)
      depends on a neural system specifically dedicated to the temporary maintenance of
      information, or instead relies on the same brain areas subserving the
      comprehension and production of language. In this study, we examined a large
      sample of adults with acquired brain lesions to identify the critical neural
      substrates underlying verbal STM and the relationship between verbal STM and
      language processing abilities. We found that patients with damage to selective
      regions of left perisylvian cortex - specifically the inferior frontal and
      posterior temporal sectors - were impaired on auditory-verbal STM performance
      (digit span), as well as on tests requiring the production and/or comprehension
      of language. These results support the conclusion that verbal STM and language
      processing are mediated by the same areas of left perisylvian cortex.

PMID- 21945330
TI  - Endovascular procedures in patients with Ehlers-Danlos syndrome: a review of
      clinical outcomes and iatrogenic complications.
AB  - BACKGROUND: Ehlers-Danlos syndrome (EDS) is a hereditary connective tissue
      disorder caused by mutations in genes involved with collagen matrix formation
      that results in weakened blood vessels. Endovascular therapy on patients with EDS
      is fraught with concerns of vessel dissection and access site complications. We
      describe the technical and clinical outcomes of patients with EDS who have
      undergone a range of endovascular procedures. METHODS: Patients with EDS
      undergoing endovascular procedures at a single-institution academic center
      between 1994 and 2010 were retrospectively reviewed. Perioperative data,
      including details of the procedure, hospital course, complications, and in
      hospital mortality, were evaluated using nonparametric tests. RESULTS: In all, 26
      patients (8 with classic EDS, 15 with hypermobile EDS, and 3 with vascular EDS)
      who underwent 48 endovascular procedures (5 diagnostic, 43 interventional; 13
      arterial, 35 venous) were identified. The indications for endovascular therapy
      included pelvic venous varices, visceral aneurysms/pseudoaneurysms,
      visceral/peripheral occlusive disease, coronary artery disease, and others.
      Median length of hospital stay was 2 days (range: 0-21 days). The rate of
      perioperative vascular injury and access site complications was low (2%), and it
      was not found to be associated with the type of vascular access technique,
      arterial versus venous procedures, target vessel site, sheath size, or method of
      closure (all: p > 0.1). Median follow-up period was 7.5 years. There were no late
      complications from the initial endovascular procedure. CONCLUSIONS: Certain
      endovascular procedures for patients with EDS can be safely performed with a low
      rate of dissections and access site complications. However, some indications
      (particularly aortic interventions) still remain to be determined.

PMID- 21945331
TI  - Development and implementation of an introductory endovascular training course
      for medical students.
AB  - BACKGROUND: Endovascular simulation has been promoted as an educational tool for
      trainees to practice procedures in a safe environment and improve basic technical
      skills. We sought to determine whether an established endovascular training
      course for medical students could increase technical proficiency, enhance
      interest in vascular surgery, and be implemented at another academic institution.
      METHODS: At Center A, medical students participated in an eight-week elective
      course with a structured curriculum comprised of weekly mentored simulator
      sessions and didactic teachings. A similar course was developed at Center B to
      train a similar cohort of students using the same high-fidelity simulator.
      Demographics and survey data, including interest in vascular surgery, were
      obtained, and pre- and postcourse graded simulator sessions on renal stent or
      iliac/superficial femoral artery stent modules were conducted. Performance was
      assessed by expert observers using a standardized global endovascular rating
      scale and objective procedural metrics collected from the simulator. RESULTS:
      Seventy-seven medical students (41 at Center A and 36 at Center B; 56 men and 21
      women) completed the course from 2007 to 2009. Parameters measured on the
      standardized global endovascular rating scale, including angiography skills, wire
      handling, and interventional criteria as well as simulator-generated metrics,
      significantly improved from pre- to postcourse values for both groups of medical
      students at the two institutions (p < 0.05). More than 94% of the students agreed
      or strongly agreed that the simulation course increased their interest in
      vascular surgery. CONCLUSION: A simulation-based endovascular course provides an
      educational tool that improves basic technical performance and increases interest
      in vascular surgery among medical students. This simple educational module
      appears to be transferable and adaptable at another institution with minimal
      modification to produce similar results.

PMID- 21945332
TI  - Long-term quality of life and mobility after prosthetic above-the-knee bypass
      surgery.
AB  - BACKGROUND: Multiple studies have addressed above-the-knee femoral artery bypass
      grafting; however, information on late quality of life (QoL) and mobility is
      scarce. We studied long-term QoL and mobility after above-the-knee bypass
      surgery. METHODS: Consecutive patients presenting with claudication, ischemic
      rest pain, or gangrene who received above-the-knee prosthetic bypass grafting
      between December 1997 and January 2003 were included in this observational study.
      Data used were recorded in a prospectively collected database of patients
      receiving Dacron and polytetrafluoroethylene (PTFE) supragenicular bypasses for
      lower limb ischemia. Primary outcomes were QoL and mobility, and secondary
      outcomes were patency and patient survival. QoL was measured with the EuroQol
      questionnaire (EQ-5D/EQ-VAS). Mobility was assessed with the Walking Impairment
      Questionnaire (WIQ) and analyzed in univariate and multivariate models. Patency
      and survival were computed with Cox regression. RESULTS: One hundred forty
      patients were treated during the study period. Sixty-nine patients (50%) died
      during follow-up, leaving 71 survivors who were asked (63 [89%] complied) to
      complete the EQ-5D/EQ-VAS and WIQ questionnaires. None of the primary outcome
      parameters (WIQ, EQ-5D, EQ-VAS) were affected by primary bypass occlusion (p =
      0.34, p = 0.44, and p = 0.27, respectively) or long-term patency (p = 0.07, p =
      0.54, and p = 0.36, respectively). Male sex was significantly associated with a
      better outcome on all primary outcome parameters. Patients with Dacron versus
      PTFE grafts had WIQ scores of 0.49 and 0.26, respectively (p = 0.01). EQ-5D
      scores of patients with Dacron and PTFE were 0.576 and 0.409 (p = 0.08) and EQ
      VAS scores were 61 and 54, respectively (p = 0.24). Graft type was not
      independently associated with occlusion, but runoff was. The 5-year and 10-year
      patient survival rates were 58% and 51%, respectively. CONCLUSIONS: In this
      study, long-term QoL and mobility did not seem to be associated with bypass
      patency, as assessed in a single late follow-up. Revision of bypasses did not
      contribute to long-term QoL and walking ability. Therefore, the necessity of
      graft surveillance and subsequent revision and/or thrombectomy in case of
      synthetic bypass failure in absence of critical limb ischemia seems to be
      questionable.

PMID- 21945333
TI  - Analysis of exhaled volatile compounds following acute superior mesenteric artery
      occlusion in a pilot rat study.
AB  - BACKGROUND: Prompt diagnosis and treatment of acute mesenteric ischemia (AMI)
      requires a high index of suspicion for timely management. Poor clinical outcomes
      and delays in surgical treatment are demonstrated even in modern clinical series.
      Recognition of exhaled volatile organic compounds (VOCs) specific to AMI may
      facilitate early detection and diagnosis and improve patient outcomes. METHODS:
      Adult Wistar rats (n = 5) were intubated and anesthetized, and control
      tracheostomy breath samples were collected using Tedlar gas sample bags.
      Intestinal ischemia was induced by placing an occlusive clip across the superior
      mesenteric artery, and breath samples were collected after 1 hour of intestinal
      ischemia and after 15 minutes of intestinal reperfusion. Gas chromatography was
      used to identify and measure levels of VOCs obtained, and measured retention
      indices were compared with known values in the Kovats retention index database.
      RESULTS: Multiple retention indices (n = 41) were noted on gas chromatography,
      representing a variety of VOCs detected. Z,Z-farnesol (C15H26O), an isoprenoid,
      was the only compound detected that was undetectable during the control phase
      (median = 0 cts/sec) but which significantly elevated during the ischemic (median
      = 34 cts/sec, range = 25-37) and reperfusion (median = 148 cts/sec, range = 42
      246) phases. Three other isoprenoid compounds (E,E-alpha-farnesene, germacrene A,
      and Z,Z-4,6,8-megastigmatriene) were also detected in all five animals, but their
      levels did not differ significantly between control, ischemic, and reperfusion
      phases. CONCLUSIONS: This pilot study demonstrates the feasibility of analyzing
      exhaled VOCs using a novel rat model for AMI. These findings may be useful for
      the development and identification of similar assays for the rapid diagnosis of
      AMI.

PMID- 21945334
TI  - Utility of bilateral Bispectral index (BIS) monitoring in a comatose patient with
      focal nonconvulsive status epilepticus.
AB  - We report the case of a patient with an extensive right cerebral hematoma
      complicated by focal nonconvulsive status epilepticus (NCSE) in whom the use of
      the new bilateral BIS-VistaTM monitor was helpful in managing profound sedation
      and antiepileptic treatment in the absence of continuous EEG monitoring (CEEG).
      The analysis of color density spectral array (CDSA) showed stereotyped changes
      indicative of recurrent focal nonconvulsive seizures (NCSz) and NCSE. We noted a
      close correlation between NCSz and BIS value changes. EEGs during working hours
      always confirmed the persistence of focal NCSE. After several days of sedation,
      CDSA disclosed a gradual resolution of NCSE that was also confirmed by
      electroencephalography. The patient died of cardiorespiratory complications a few
      days later.

PMID- 21945335
TI  - The effect of antigen size on the immunogenicity of antigen presenting cell
      targeted DNA vaccine.
AB  - Directing antigens to antigen presenting cells (APCs) has been demonstrated to be
      an efficient strategy to enhance immune responses induced by DNA vaccination.
      Fusion of antigens to cytotoxic T-Lymphocyte antigen 4 (CTLA4), a ligand of B7
      molecules on the surfaces of APCs with strong binding affinity, enhanced the
      immunogenicities of antigens in various degrees. To investigate the relationship
      between antigen size and the immunogenicity of CTLA4 fusion DNA vaccine, we
      constructed CTLA4 targeted fusion anti-caries DNA vaccines containing different
      size of antigens. In vivo and in vitro experiments showed that CTLA4 fusion with
      smaller antigen induced stronger humoral immune responses and had higher affinity
      to B7-expressed cells than fusion with larger antigen. In conclusion, antigen
      size is one of the important factors regulating the potency of humoral immune
      response induced by CTLA4 targeted DNA vaccines.

PMID- 21945336
TI  - Normalized global alignment for protein sequences.
AB  - Global alignment is used to compare proteins in different fields, for example in
      phylogenetic research. In order to reduce the length and composition dependence
      of global alignment scores, Z-score is computed with a Monte-Carlo algorithm.
      This technique requires a great number of sequence alignments on shuffled
      sequences, leading to a high computational cost. In this work, a normalized
      global alignment score is introduced in order to correct the length dependence of
      global alignments. This score is defined as the best ratio between the score of
      an alignment and its length, and an algorithm to compute it based on fractional
      programming is implemented. The properties and effectiveness of normalized global
      alignment applied to protein comparison are analyzed. Experiments with proteins
      selected from the SCOP ASTRAL database were run to study relationship of
      normalized global alignment with Z-score and performance in homologous detection.
      Results show that normalized global alignment has a computational cost equivalent
      to 2.5 Needleman-Wunsch runs and a linear relationship with Z-score. This
      linearity allows us to use normalized global alignment as a cheap substitute to a
      computationally expensive Z-score. Experiments show that normalized global
      alignment improves the ability to identify homologous proteins. Software used to
      compute normalized global alignments is available from
      http://www3.uji.es/~peris/nga.

PMID- 21945338
TI  - Multicopy plasmid stability: revisiting the dimer catastrophe.
AB  - In this study, we have constructed a stochastic simulation of the replication and
      distribution of the bacterial multicopy plasmid ColE1 in a population of
      exponentially growing cells. It is assumed that ColE1 is randomly distributed
      between daughter cells at division such that copy number is a critical
      determinant of plasmid loss. High copy number is threatened by plasmid dimers,
      which arises initially by homologous recombination and accumulate by replication
      in a process known as the 'dimer catastrophe'. Summers et al. (1993) modelled
      this process and demonstrated that the accumulation of dimers is limited by the
      metabolic load that they exert on their hosts. ColE1 also encodes the cer site,
      at which host-encoded proteins act to convert dimers to monomers by site-specific
      recombination. The cer site also encodes a regulatory RNA, Rcd, whose synthesis
      from plasmid dimers triggers a checkpoint that delays cell division, presumably
      allowing sufficient time for dimer resolution. Here we have developed the
      original dimer catastrophe model by incorporating copy number variance with a
      stochastic model of plasmid replication. We demonstrate that the Rcd checkpoint
      is necessary when the rate of dimer resolution is slow. Our results indicate that
      dimers over-replicate compared to monomers, suggesting a mechanism for their
      increased metabolic load. We find that the effect of dimers on plasmid stability
      is significantly less severe than suggested by the original model. Consequently,
      we propose that the primary role of dimer resolution and the Rcd checkpoint is to
      reduce the metabolic burden imposed by the plasmid in a recombinogenic host,
      rather than to ensure plasmid stability.

PMID- 21945337
TI  - Optimality in DNA repair.
AB  - DNA within cells is subject to damage from various sources. Organisms have
      evolved a number of mechanisms to repair DNA damage. The activity of repair
      enzymes carries its own risk, however, because the repair of two nearby lesions
      may lead to the breakup of DNA and result in cell death. We propose a
      mathematical theory of the damage and repair process in the important scenario
      where lesions are caused in bursts. We use this model to show that there is an
      optimum level of repair enzymes within cells which optimises the cell's response
      to damage. This optimal level is explained as the best trade-off between fast
      repair and a low probability of causing double-stranded breaks. We derive our
      results analytically and test them using stochastic simulations, and compare our
      predictions with current biological knowledge.

PMID- 21945339
TI  - Pedicled (antegrade) SUPBRA flap - for wound cover on volar aspect of thumb.
AB  - A dictum of reconstruction is to replace like with like. Therefore, glabrous skin
      is best replaced with like tissue from the palm or the soles of the feet. We have
      previously presented our experience with free tissue from the palm based on the
      superficial palmer branch of the radial artery to reconstruct defects on the
      volar aspect of the digits following the original description of this flap by
      Kamei et al. There are situations where an antegrade pedicled flap from this area
      lends well as a choice for reconstruction. We describe the use of a pedicled flap
      from this axis for a defect on the radial aspect of the thumb and we believe it
      is the first report of its kind.

PMID- 21945340
TI  - Anthropometric evaluation of bilateral cleft lip nose with cone beam computed
      tomography in early childhood: Estimation of nasal tip collapse.
AB  - BACKGROUND: Nasal tip features of cleft lip nose cannot be defined well using
      conventional measurement methods. Therefore, we developed a new method in which
      vertical nasal tip (the pronasale) position is evaluated based on the Frankfurt
      Horizontal plane. This measurement was applied to bilateral cleft lip patients in
      early childhood. METHODS: Cone beam computed tomography (CT) records of bilateral
      cleft lip patients after primary rhinoplasty aged from 5 to 8 years (n = 13) were
      investigated retrospectively. As age-matched controls, data from a normal group
      (n = 17) and complete unilateral cleft lip group after primary rhinoplasty (n =
      19) were included. In each group, nasolabial angle (beta), nasal tip angle
      (alpha), nasal width (al-al), columellar length (sn-c' ), nasal tip protrusion
      (sn-prn), and vertical nasal tip position (sn'-prn'/sn'-n') were investigated.
      RESULTS: With the exception of vertical nasal tip position and nasal width, the
      measurement data of the bilateral cleft lip patients were acceptable. In the
      bilateral cleft lip group, however, vertical nasal tip position was significantly
      higher and nasal width was significantly larger than those in the normal and
      unilateral groups (P < 0.0001 and P = 0.0298; P = 0.0001 and P = 0.0002,
      respectively). CONCLUSIONS: In cleft lip nose, the lower lateral cartilage that
      normally composes the nasal tip domes is splayed out, causing cephalic
      positioning of the pronasale. Nasal tip collapse was more severe in bilateral
      cleft lip than in the unilateral group. These results were compatible with the
      fact that many bilateral cleft lip patients require augmentation rhinoplasty
      after adolescence even after primary rhinoplasty.

PMID- 21945341
TI  - Iterative design and testing of a hand-held, non-contact wound measurement
      device.
AB  - A variety of wound measurement techniques are available to clinicians. Options
      range from relatively simple and inexpensive to complex, expensive devices. An
      iterative design approach was used to evaluate and improve performance and
      clinical utility of a new wound measurement device (WMD). The design was based
      upon a commercially available Smartphone. Accuracy was assessed using bench
      testing and reliability of area measurements was determined using multiple
      evaluators. Clinical utility was investigated by deploying the WMD during wound
      rounds in a rehabilitation hospital. Accuracy testing revealed an average error
      <2% at 0 degrees  or skew and an average error of 4.28% at 10 degrees  of skew.
      The intra-rater reliability exceeded 0.975 for all raters and inter-rater
      reliability was 0.966. Clinical utility testing provided the opportunity to
      address several usability concerns including the software interface and
      computation times. The accuracy and reliability of a new, non-contact wound
      measurement device exceeded that of other manual techniques and were, at least,
      equivocal to other computer-based technologies. Some limitations of using a
      Smartphone were identified by the clinicians that can be addressed by the more
      advanced processing power of newer technology. Overall, the WMD was shown to have
      the potential as a useful clinical tool.

PMID- 21945342
TI  - Common genetic mutations in the start codon of the SDH subunit D gene among
      Chinese families with familial head and neck paragangliomas.
AB  - Head and neck paragangliomas (HNPGLs) are rare, and frequently associated with
      germline mutations of the succinate dehydrogenase (SDH) genes, especially for
      familial cases. The purpose of the study is to explore SDH mutations in Chinese
      families with familial HNPGLs in Taiwan. Four unrelated families with familial
      HNPGLs were screened for germline mutations in the SDHB, SDHC and SDHD genes by
      direct sequencing. One hundred healthy subjects without a diagnosis or family
      history of HNPGLs were screened as normal controls. Immunohistochemistry with
      SDHB antibody was performed for a carotid body tumor. Two allele variants were
      identified, including p.Met1Val (c.1A>G) in the SDHD gene in one family and
      p.Met1Ile (c.3G>C) in the SDHD gene in the other three families. Both variants
      are considered pathogenic because of the absence of these variants in 100 normal
      controls, 100% evolutionary conservation of the p.Met1 residue, co-segregation of
      the variants with the phenotype of HNPGL in pedigrees, and predicted abolishment
      of the translation start site. The tumor cells obtained from one proband
      harboring c.3G>C mis-sense mutation were weak diffuse staining in the cytoplasm
      of tumors cells. This study demonstrates that two mis-sense mutations at the
      start codon of the SDHD gene, including p.Met1Val (c.1A>G) and p.Met1Ile
      (c.3G>C), might be mutation hotspots in Chinese patients with familial HNPGLs.

PMID- 21945343
TI  - A high HIF-1alpha expression genotype is associated with poor prognosis of upper
      aerodigestive tract carcinoma patients.
AB  - The aim of the present study was to evaluate the role of HIF-1alpha genetic
      polymorphisms and protein expression in the development of metastasis in upper
      aerodigestive tract cancer (UADTC) patients. The expression of pro-angiogenic
      markers was also evaluated. Protein expression was analysed using
      immunohistochemistry, and RFLP analysis was used to investigate HIF-1alpha C1779T
      and G1790A polymorphisms in 52 patients with UADTC. Primary lesions were divided
      into 2 groups according to the absence or presence of metastasis. Lymph node
      samples were divided into 3 groups: metastatic lymph nodes, non-metastatic lymph
      nodes (both derived from patients with metastatic disease), and control lymph
      nodes, which were obtained from patients without any metastasis. The allele T was
      more frequently found in patients with metastatic disease. HIF-1alpha protein
      expression in the lymph nodes was increased in the presence of the T allele.
      Metastatic lymph nodes showed lower levels of HIF-1alpha, VEGFR1, and MMP-9
      proteins compared to lymph nodes without metastasis, while VEGFR2 protein levels
      were increased. In agreement, HIF-1alpha expression was correlated with MMP-9.
      Cox regression analysis demonstrated that higher HIF-1alpha and MMP-9 protein
      expression levels and GA and GG genotypes were associated with poor survival. Our
      findings show that the C1772T and G1790A polymorphisms of the HIF-1alpha gene are
      associated with increased expression of the HIF-1alpha protein in UADTC. The
      present data indicate that non-metastatic tissues express higher levels of HIF
      1alpha, VEGFR1, and MMP-9, while in metastatic lymph nodes, VEGFR2 protein
      expression is elevated. The present study also shows that the HIF-1alpha G1790A
      polymorphism and its protein expression have an impact on the prognosis of UADTC
      patients.

PMID- 21945344
TI  - Category label effects on Chinese children's inductive inferences: modulation by
      perceptual detail and category specificity.
AB  - Inductive generalization of novel properties to same-category or similar-looking
      objects was studied in Chinese preschool children. The effects of category labels
      on generalizations were investigated by comparing basic-level labels,
      superordinate-level labels, and a control phrase applied to three kinds of
      stimulus materials: colored photographs (Experiment 1), realistic line drawings
      (Experiment 2), and cartoon-like line drawings (Experiment 3). No significant
      labeling effects were found for photos and realistic drawings, but there were
      significant effects for cartoon-like drawings. Children made mostly (>70%)
      category-based inferences about photographs whether or not labels were provided
      (Experiment 1). Children showed a bias toward category-based inferences about
      realistic drawings (Experiment 2) but did so only when labels were provided.
      Finally, children made mostly appearance-based generalizations for cartoon-like
      drawings (Experiment 3). However, labels (basic or superordinate level) reduced
      appearance-based responses. Labeling effects did not depend on having identical
      labels; however, identical superordinate labels were more effective than
      different basic-level labels for the least informative stimuli (i.e., cartoons).
      Thus, labels sometimes confirm the identity of ambiguous items. This evidence of
      labeling effects in Mandarin-speaking Chinese children extends previous findings
      beyond English-speaking children and shows that the effects are not narrowly
      culture and language specific.

PMID- 21945345
TI  - Patterns of strengths and weaknesses in children's knowledge about fractions.
AB  - The purpose of this study was to explore individual patterns of strengths and
      weaknesses in children's mathematical knowledge about common fractions. Tasks
      that primarily measure either conceptual or procedural aspects of mathematical
      knowledge were assessed with the same children in their fourth- and fifth-grade
      years (N=181, 56% female and 44% male). Procedural knowledge was regressed on
      levels of conceptual knowledge, and vice versa, to obtain residual scores.
      Residual scores capture variability in each kind of math knowledge that is not
      shared with the other type of knowledge. Cluster analysis using residuals
      indicated four distinct knowledge profiles in fourth graders: (a) higher than
      expected conceptual knowledge and relatively lower procedural knowledge, (b)
      relatively lower conceptual knowledge and higher procedural knowledge, (c) lower
      concepts but expected levels of procedural knowledge, and (d) relatively higher
      than expected levels of both procedural and conceptual knowledge. In fifth grade,
      another cluster emerged that showed lower procedures but expected levels of
      conceptual knowledge. In general, students with relatively lower than expected
      conceptual knowledge showed poorer accuracy on measures used to form the clusters
      and also word problem setups and estimation of sums. Implications for explaining
      seemingly conflicting results from prior work across studies are discussed.

PMID- 21945346
TI  - Age-related changes in the three-way correlation between anterior hippocampus
      volume, whole-brain patterns of encoding activity and subsequent context
      retrieval.
AB  - Age-related declines in memory for context have been linked to volume loss in the
      hippocampal head (HH) with age. However, it remains unclear how this volumetric
      decline correlates with age-related changes in whole-brain activity during
      context encoding, and subsequent context retrieval. In the current study we
      examine this. We collected functional magnetic resonance imaging data in young
      and older adults during the encoding of item, spatial context and temporal
      context. HH volume and subsequent retrieval performance was measured in all
      participants. In young adults only there was a positive three-way correlation
      between larger HH volumes, better memory retrieval, and increased activity in
      right hippocampus, right ventrolateral prefrontal cortex (VLPFC) and midline
      brain regions during episodic encoding. In contrast, older adults exhibited a
      positive three-way association between HH volume, generalized activity in
      bilateral hippocampus and dorsolateral PFC across all encoding tasks, and
      subsequent spatial context retrieval. Young adults also engaged this network, but
      only during the most difficult temporal context encoding task and activity in
      this network correlated with subsequent temporal context retrieval. We conclude
      that age-related volumetric reductions in HH disrupted the structure-function
      association between the hippocampus and activity in the first general encoding
      network recruited by young adults. Instead, older adults recruited those brain
      regions young adults only engaged for the most difficult temporal task, at lower
      difficulty levels. This altered pattern of association correlated with spatial
      context retrieval in older adults, but was not sufficient to maintain context
      memory abilities overall.

PMID- 21945347
TI  - Biomedical events extraction using the hidden vector state model.
AB  - OBJECTIVE: Biomedical events extraction concerns about events describing changes
      on the state of bio-molecules from literature. Comparing to the protein-protein
      interactions (PPIs) extraction task which often only involves the extraction of
      binary relations between two proteins, biomedical events extraction is much
      harder since it needs to deal with complex events consisting of embedded or
      hierarchical relations among proteins, events, and their textual triggers. In
      this paper, we propose an information extraction system based on the hidden
      vector state (HVS) model, called HVS-BioEvent, for biomedical events extraction,
      and investigate its capability in extracting complex events. METHODS AND
      MATERIAL: HVS has been previously employed for extracting PPIs. In HVS-BioEvent,
      we propose an automated way to generate abstract annotations for HVS training and
      further propose novel machine learning approaches for event trigger words
      identification, and for biomedical events extraction from the HVS parse results.
      RESULTS: Our proposed system achieves an F-score of 49.57% on the corpus used in
      the BioNLP'09 shared task, which is only 2.38% lower than the best performing
      system by UTurku in the BioNLP'09 shared task. Nevertheless, HVS-BioEvent
      outperforms UTurku's system on complex events extraction with 36.57% vs. 30.52%
      being achieved for extracting regulation events, and 40.61% vs. 38.99% for
      negative regulation events. CONCLUSIONS: The results suggest that the HVS model
      with the hierarchical hidden state structure is indeed more suitable for complex
      event extraction since it could naturally model embedded structural context in
      sentences.

PMID- 21945348
TI  - Autophagy in cancer: having your cake and eating it.
AB  - Autophagy, one of two major intracellular degradation pathways, plays a critical
      role in energy homeostasis and the quality control of macromolecules and
      intracellular organelles. Previous work has demonstrated the importance of
      autophagy in maintaining cellular fitness, both in healthy and stressful
      conditions, revealing the complex interplay between autophagy and other stress
      responsive phenotypes. The complex outcomes of stress-responsive autophagy confer
      on it both pro- and anti-tumourigenic roles, depending on the cellular and
      environmental context. Furthermore, recent findings that functionally link
      autophagy to the tumour suppressor mechanism, cellular senescence, have revealed
      a new role of autophagy in cancer biology. In this review we summarise the
      current evidence on the relationship between autophagy and cancer, with a focus
      on its role in senescence.

PMID- 21945350
TI  - Raman spectroscopic study on archaeological glasses in Thailand: ancient Thai
      glass.
AB  - Glasses have been used as ornamental and decorative objects in Thailand for
      several hundred years as seen in archaeological artifacts, such as glass beads
      found throughout the regions. Decorative glasses can generally be seen as
      architectural components in Buddhist temples and old-styled palaces. They came in
      various colors ranging from transparent to amber, blue, green and red of
      different shades and tones. Fragments of archaeological glass samples were
      characterized for the first time using Raman spectrophotometer with the aim of
      obtaining information that would lead to the identification of the glass samples
      by means of laser scattering. The samples were also investigated using other
      techniques, such as proton induced X-ray emission spectroscopy, scanning electron
      microscopy cooperated with energy dispersive X-ray fluorescence spectrometer and
      synchrotron radiation to induced X-ray fluorescence. The results showed that they
      were mostly lead-silica based glasses whose colors were induced by metal ions.
      The differences in chemical compositions were confirmed by Raman signature
      spectra.

PMID- 21945349
TI  - Emerging importance of ALK in neuroblastoma.
AB  - Since the original descriptions of gain-of function mutations in anaplastic
      lymphoma kinase (ALK), interest in the role of this receptor tyrosine kinase in
      neuroblastoma development and as a potential therapeutic target has escalated. As
      a group, the activating point mutations in full-length ALK, found in
      approximately 8% of all neuroblastoma tumors, are distributed evenly across
      different clinical stages. However, the most frequent somatic mutation, F1174L,
      is associated with amplification of the MYCN oncogene. This combination of
      features appears to confer a worse prognosis than MYCN amplification alone,
      suggesting a cooperative effect on neuroblastoma formation by these two proteins.
      Indeed, F1174L has shown more potent transforming activity in vivo than the
      second most common activating mutation, R1275Q, and is responsible for innate and
      acquired resistance to crizotinib, a clinically relevant ALK inhibitor that will
      soon be commercially available. These advances cast ALK as a bona fide
      oncoprotein in neuroblastoma and emphasize the need to understand ALK-mediated
      signaling in this tumor. This review addresses many of the current issues
      surrounding the role of ALK in normal development and neuroblastoma pathogenesis,
      and discusses the prospects for clinically effective targeted treatments based on
      ALK inhibition.

PMID- 21945351
TI  - Vibrational spectroscopy and ionic conductivity of polyethylene oxide-NaClO4-CuO
      nanocomposite.
AB  - Structure, morphology and thermal properties of polyethylene oxide (PEO) with
      sodium perchlorate (NaClO(4)) as electrolytic salt have been investigated by
      incorporating cupric monoxide (CuO) nanoparticles. Monoclinic CuO affects melting
      and glass transition temperatures of PEO-NaClO(4). Crystallinity and free ion
      concentration change with the variation of CuO concentration. The maximum ionic
      conductivity is observed for 10 wt.% CuO. Ionic conductivity follows Arrhenius
      type behavior as a function of temperature.

PMID- 21945352
TI  - Pyrogallol red oxidation induced by superoxide radicals: application to evaluate
      redox cycling of nitro compounds.
AB  - The bleaching of the pyrogallol red (PGR) dye mediated by superoxide anion
      radicals (O(2)(-)) generated from the xanthine/xanthine oxidase system (X/XO) was
      studied by UV-visible spectrophotometry. The absorption band (at 540 nm) of PGR
      quickly decreased in the presence of X/XO, implying an efficient reaction of
      O(2)(-) with PGR. The process was unaffected by catalase (CAT), but completely
      abolished by superoxide dismutase (SOD). A mechanism of the reaction involving
      the consumption of one PGR molecule by two O(2)(-) to generate one molecule of
      H(2)O(2) is proposed. PGR was used as a probe to estimate the rate of O(2)(-)
      generation in redox cycling reactions of a series of nitro compounds mediated by
      rat liver microsomes. The consumption of PGR induced by the redox cycling of
      nitrofurantoin was totally eliminated by the addition of SOD but unaffected by
      CAT. The initial rate of consumption of PGR mediated by the redox cycling of
      others nitro derivatives follows the order: furazolidindione > nitrofurantoin >
      nifurtimox > benznidazole > chloramphenicol. We concluded that PGR can be used as
      a probe to estimate the release of O(2)(-) from enzymatic systems or from the
      redox cycling of nitro compounds.

PMID- 21945353
TI  - A general insert label for peptide display on chimeric filamentous
      bacteriophages.
AB  - The foreign insert intended to be displayed via recombinant phage proteins can
      have a negative effect on protein expression and phage assembly. A typical
      example is the case of display of peptides longer than 6 amino acid residues on
      the major coat protein, protein VIII of the filamentous bacteriophages M13 and
      fd. A solution to this problem has been the use of "two-gene systems" generating
      chimeric phages that concomitantly express wild-type protein VIII along with
      recombinant protein VIII. Although the two-gene systems are much more permissive
      in regard to insert length and composition, some cases can still adversely affect
      phage assembly. Although these phages genotypically contain the desired DNA of
      the insert, they appear to be phenotypically wild type. To avoid false-negative
      results when using chimeric phages in binding studies, it is necessary to confirm
      that the observed lack of phage recognition is not due to faulty assembly and
      display of the intended insert. Here we describe a strategy for generating
      antibodies that specifically recognize recombinant protein VIII regardless of the
      nature of its foreign insert. These antibodies can be used as a general monitor
      of the display of recombinant protein VIII into phage particles.

PMID- 21945354
TI  - A careful evaluation of scout CT lateral radiograph may prevent unreported
      vertebral fractures.
AB  - OBJECTIVES: Our purpose was to review scout CT lateral radiographs to reveal
      osteoporotic vertebral fractures unreported by radiologists and to explore scout
      CT as a potential diagnostic tool in the detection of vertebral fractures.
      METHODS: We considered 500 patients (303 males, 197 females, age 64.6+/-13.5 year
      old). Our investigation was firstly focused on scout CT lateral images to detect
      vertebral fractures with a combined semiquantitative and quantitative diagnostic
      approach. Findings addressed to vertebral fracture were subsequently confirmed by
      multiplanar sagittal CT reconstructions. Whenever a vertebral fracture was
      discovered the radiologist report was read and a collection of patient anamnesis
      followed to understand whether fractures were already known. RESULTS: In 44/500
      patients (8.8%) the evaluation on scout CT was incomplete or limited for
      patient/technical-based conditions, and 15 were excluded from the analysis. In
      67/485 patients (13.8%) 99 vertebral fractures were detected. Among 67 fractured
      patients only 18 (26.9%) were previously diagnosed by radiologists. However, in
      the clinical history of 32 patients vertebral fractures were already known.
      CONCLUSIONS: The perception and sensibility to vertebral fractures among
      radiologists are still poor when the assessment of the spine is not the aim of
      the examination. Short time spent for the evaluation of scout CT lateral
      radiographs could improve our accuracy.

PMID- 21945355
TI  - Hyperecho in ultrasound images during high-intensity focused ultrasound ablation
      for hepatocellular carcinomas.
AB  - High-intensity focused ultrasound (HIFU) is a noninvasive method that can cause
      complete coagulation necrosis without requiring the insertion of any instruments.
      The hyperechoic grayscale change (hyperechoic region) is used as a sign that the
      treated lesion has been completely coagulated. The purpose of this study was to
      evaluate the first hyperechoic region during treatment using HIFU ablation
      according to various conditions, such as the sonication power, the depth of the
      tumor from the surface of the skin, and the shield rate. HIFU treatment was
      performed in 20 patients. The HIFU system (Chongqing Haifu Tech, Chongqing,
      China) was used under ultrasound guidance. Complete coagulation was achieved in
      17 cases. Hyperechoic region were detected after HIFU ablation in 17 patients.
      The size of the hyperechoic region at a depth of >50 mm was significantly smaller
      than that at a depth of <=50 mm. The number and power of the sonications for
      areas at a depth of >50 mm were significantly larger than those for areas at a
      depth of <=50 mm. The number and power in cases with a shield rate of 31-60% were
      significantly larger than those in cases with a shield rate of 0-30%. When the
      shield rate was 0%, a hyperechoic region occurred, even when a maximum sonication
      power was not used. In all three cases with tumors located at a depth of greater
      than 70 mm and a shield rate of larger than 60%, a hyperechoic region was not
      seen. In conclusion, hyperechoic regions are easy to visualize in cases with
      tumors located at a depth of <=50 mm or shield rates of 0-30%.

PMID- 21945357
TI  - Medical or surgical therapy for gastroesophageal reflux disease?

PMID- 21945358
TI  - Armed conflict women and girls who are pregnant, infants and children; a
      neglected public health challenge. What can health professionals do?
AB  - Without security, adequate healthcare is not possible. Armed conflicts continue
      to be waged with pregnant women and girls, babies and children affected most.
      Most countries in conflict are poorly resourced and their mortality and morbidity
      statistics so much higher than rich countries that nothing short of a global
      revolution to create equity is going to solve the problem. When the arms trade is
      added in and analysed the maternal and child mortality rates for those countries
      exporting most of these killing machines is so much lower than the countries in
      which they are used that we have an ethical issue that must be addressed by
      health professionals. Armed conflict is probably the most serious global public
      health challenge and two solutions are proposed. Health professionals have a
      major voice and must support the currently progressing Arms Trade Treaty and call
      for more effective protection for healthcare in areas of conflict.

PMID- 21945359
TI  - Maternal diabetes and perinatal programming.
AB  - Alterations of the intrauterine and neonatal environment may predispose for
      disorders and diseases throughout later life (perinatal programming). Especially,
      hormones and nutrients are dose-dependent organizers of the developing organism.
      Studies in offspring of diabetic mothers (ODM) have paradigmatically contributed
      to the perception of this developmental principle and our understanding of causal
      mechanisms. Fetal and neonatal hyperinsulinism in consequence of materno-fetal
      hyperglycaemia is the pathognomic feature in ODM. Epidemiological, clinical, as
      well as experimental data indicate that both insulin and glucose, when occurring
      in elevated concentrations during perinatal life, may epigenetically program a
      predisposition for obesity and diabetes later on. Similar may occur due to pre-
      and neonatal overfeeding. From a clinical point of view, avoidance of materno
      fetal overnutrition, universal diabetes screening in all pregnant women and
      adequate therapy of all forms of diabetes during pregnancy, as well as avoidance
      of neonatal overfeeding are therefore recommended. These measures might serve as
      causal approaches of a genuine prevention to the benefit of long-term offspring
      health.

PMID- 21945360
TI  - Follow-up of the survivors of congenital diaphragmatic hernia.
AB  - INTRODUCTION: Survivors of congenital diaphragmatic hernia have increased with
      the introduction of new treatment modalities and have been reported to experience
      ongoing medical morbidity until adulthood. AIM: To describe the long-term
      functional impact of congenital diaphragmatic repair on the survivors of a single
      institution cohort of newborns over a 14-year period. METHODS: The follow up
      medical charts of 39 congenital diaphragmatic hernia survivors treated at a
      tertiary neonatal intensive care unit, from January 1997 to December 2010, were
      analyzed. RESULTS: The median age at follow up was 70 (4-162) months.
      Gastrointestinal sequelae were the most common with 12 (30.7%) patients affected
      by failure to thrive. Chronic lung disease occurred in 5 (12.8%) patients,
      neurodevelopmental delay in 5 (12.8%), musculoskeletal sequelae in 6 (15.3%),
      recurrence of hernia in 4 (10.2%) and 2 (7.6%) were deceased. CONCLUSION:
      Congenital diaphragmatic hernia survivors are a group of patients that requires
      long term periodic follow up in a multidisciplinary setting to provide adequate
      support and improve their quality of life.

PMID- 21945356
TI  - RNA therapeutics targeting osteoclast-mediated excessive bone resorption.
AB  - RNA interference (RNAi) is a sequence-specific post-transcriptional gene
      silencing technique developed with dramatically increasing utility for both
      scientific and therapeutic purposes. Short interfering RNA (siRNA) is currently
      exploited to regulate protein expression relevant to many therapeutic
      applications, and commonly used as a tool for elucidating disease-associated
      genes. Osteoporosis and their associated osteoporotic fragility fractures in both
      men and women are rapidly becoming a global healthcare crisis as average life
      expectancy increases worldwide. New therapeutics are needed for this increasing
      patient population. This review describes the diversity of molecular targets
      suitable for RNAi-based gene knock down in osteoclasts to control osteoclast
      mediated excessive bone resorption. We identify strategies for developing
      targeted siRNA delivery and efficient gene silencing, and describe opportunities
      and challenges of introducing siRNA as a therapeutic approach to hard and
      connective tissue disorders.

PMID- 21945361
TI  - Asynchrony of mother-infant hypothalamic-pituitary-adrenal axis activity
      following extinction of infant crying responses induced during the transition to
      sleep.
AB  - This study examines change in the synchrony between mothers' and infants'
      physiology as 25 infants (11 males; 4 to 10 months of age) participate in a 5-day
      inpatient sleep training program in which they learn to self-settle through
      extinction of crying responses during the transition to sleep. The mothers' and
      infants' experience during the extinction protocol was "yoked" by the infants'
      behavioral signaling during the sleep transition period. Saliva was sampled for
      mothers and infants at initiation of infants' nighttime sleep and following
      infants' falling to sleep on two program days and later assayed for cortisol. As
      expected on the first day of the program, mothers' and infants' cortisol levels
      were positively associated at initiation of nighttime sleep following a day of
      shared activities. Also, when infants expressed distress in response to the sleep
      transition, mother and infant cortisol responses were again positively
      associated. On the third day of the program, however, results showed that
      infants' physiological and behavioral responses were dissociated. They no longer
      expressed behavioral distress during the sleep transition but their cortisol
      levels were elevated. Without the infants' distress cue, mothers' cortisol levels
      decreased. The dissociation between infants' behavioral and physiological
      responses resulted in asynchrony in mothers' and infants' cortisol levels. The
      findings are discussed in relation to understanding the determinants and
      implications of maternal-infant physiological synchrony in early childhood.

PMID- 21945362
TI  - Melatonin treatment in children with therapy-resistant monosymptomatic nocturnal
      enuresis.
AB  - OBJECTIVE: To evaluate the effects of exogenous melatonin on the frequency of wet
      nights, on the sleep-wake cycle, and on the melatonin profile in children with
      therapy-resistant MNE. PATIENTS AND METHODS: 24 patients were included. Patients
      had to maintain a diary including time of sleep and arousal, and whether they had
      a dry or a wet bed in the morning. We measured baseline melatonin profiles in
      saliva. Hereafter, patients were randomized to synthetic melatonin or placebo.
      After 3 and 6 months we evaluated the frequency of enuresis and the melatonin
      profiles. RESULTS: 11 patients were randomized to melatonin, 13 to placebo. We
      evaluated melatonin profiles of 7 patients in the melatonin group and of 8 in the
      placebo group. We observed a change in profile in the melatonin group, but we did
      not observe a difference in the sleep-wake cycle or the frequency of wet nights
      in either group. CONCLUSION: This is the first time exogenous melatonin has been
      evaluated in the treatment of MNE. Although we observed a change in melatonin
      profile after the use of exogenous melatonin, we did not observe a change in
      enuresis frequency or in the sleep-wake cycle of this select group of patients.

PMID- 21945363
TI  - Is parental anxiety and coping associated with girls' distress during a VCUG?
      Preliminary findings.
AB  - PURPOSE: We investigated the relationship between parental anxiety/coping
      strategies and girls' distress during VCUGs. METHODS: Parents of 32 girls (age 4
      10, mean 5.8 years) completed a trait anxiety measure and a measure of parental
      reactions to children's distress. Post procedure, children, parents and radiology
      staff rated the level of anxiety, fear, pain and discomfort. RESULTS: Trends
      indicated that parents who reported increased anxiety rated their children as
      experiencing increased distress (r = 0.27, p = 0.071), similarly for medical
      staff ratings (r = 0.28, p = 0.061). Parents with lower trait anxiety scores
      reported using more emotion- and problem-focused coping strategies (r = -0.37 and
      r = -0.40, p < 0.05, respectively). These were related to children experiencing
      less procedural distress (r = -0.30, p = 0.054; r = -0.33, p = 0.037,
      respectively) and parents rated as less anxious by staff (r = -0.40, p = 0.014; r
      = -0.31, p = 0.047, respectively). CONCLUSIONS: There was a trend toward parental
      anxiety being related to their child's distress during VCUG. Parental coping
      strategies resulted in less distress among children and parents. Teaching coping
      techniques might obviate the need for sedation and help children deal with future
      stressors.

PMID- 21945364
TI  - Transpubic posterior urethroplasty via perineal approach in children: a new
      technique.
AB  - OBJECTIVE: To evaluate a new technique of transpubic urethroplasty via perineal
      approach for management of pelvic fracture urethral distraction defects (PFUDD)
      in children. METHODS: Of 78 children undergoing posterior urethroplasty for
      PFUDD, 12 (15.4%) had a short urethra that could not bridge the gap (>5 cm) for a
      tension-free anastomosis. Age ranged from 5.2 to 12 years (median = 8.5 years).
      The median distraction defect length was 4.8 cm (range 3.7-6.4 cm). For the
      latter group, the new technique of transpubic posterior urethroplasty via
      perineal approach was performed. The first follow-up visit was scheduled 1 month
      after suprapubic catheter removal. Radiological studies and uroflowmetry were
      repeated at 6-month intervals for 1 year and once yearly thereafter. RESULTS:
      Patients were followed up for a period of 6 months to 5 years with a mean of 2.7
      years. Mean operative time was 2.5 h (range 1.9-3.2 h) with a mean blood loss of
      200 ml (range 50-640 cc) and the mean hospital stay was 4 days. All 12 children
      had a good urinary stream over the follow-up period; 3/12 (25%) developed stress
      urinary incontinence that resolved within 6 months postoperatively; 9/12 (75%)
      complained of (retracted) short penis. CONCLUSIONS: Transpubic urethroplasty via
      perineal approach is a feasible technique for management of complex PFUDD in
      children, and presents many advantages over other routes.

PMID- 21945365
TI  - Patients with epilepsy and psychogenic non-epileptic seizures: an inpatient video
      EEG monitoring study.
AB  - Seizure and EEG characteristics of patients with epilepsy and concomitant
      psychogenic non-epileptic seizures (PNES) were compared to age and sex matched
      controls with epilepsy alone in a retrospective case control study. 39 patients
      with clearly documented epileptic and non-epileptic events were compared to 78
      age and sex matched controls, sequentially admitted for video-EEG monitoring with
      documentation of epilepsy alone. Frontal seizures were higher in prevalence in
      patients with PNES who had concomitant epilepsy (P<0.001), while temporal
      seizures were higher in prevalence in patients with epilepsy alone (P<0.04). On
      regression analysis, the odds of having a frontal seizure was found to be
      significantly lower in the epilepsy alone group compared to the epilepsy+PNES
      group (odds ratio 0.13, 95% CI, 0.033-0.51). This significant association between
      frontal lobe epilepsy and PNES may be related to misattribution of frontal
      seizures for PNES events, or may reflect frontal lobe cortical dysfunction in
      this subgroup.

PMID- 21945366
TI  - Surfactant and its role in the pathobiology of pulmonary infection.
AB  - Pulmonary surfactant is a complex surface-active substance comprised of key
      phospholipids and proteins that has many essential functions. Surfactant's unique
      composition is integrally related to its surface-active properties, its critical
      role in host defense, and emerging immunomodulatory activities ascribed to
      surfactant lipids. Together these effector functions provide for lung stability
      and protection from a barrage of potentially virulent infectious pathogens.

PMID- 21945367
TI  - alpha-Tocopherol injections in rats up-regulate hepatic ABC transporters, but not
      cytochrome P450 enzymes.
AB  - The role of hepatic xenobiotic regulatory mechanisms in modulating hepatic alpha
      tocopherol concentrations during excess vitamin E administration remains unclear.
      We hypothesized that increased hepatic alpha-tocopherol would cause a marked
      xenobiotic response. Thus, we assessed cytochrome P450 oxidation systems (phase
      I), conjugation systems (phase II), and transporters (phase III) after daily
      alpha-tocopherol injections (100mg/kg body wt) for up to 9days in rats. alpha
      Tocopherol injections increased hepatic alpha-tocopherol concentrations nearly 20
      fold, along with a 10-fold increase in the hepatic alpha-tocopherol metabolites
      alpha-CEHC and alpha-CMBHC. Expression of phase I (CYP3A2, CYP3A1, CYP2B2) and
      phase II (SULT2A1) proteins and/or mRNAs was variably affected by alpha
      tocopherol injections; however, expression of phase III transporter genes was
      consistently changed by alpha-tocopherol. Two liver efflux transporter genes,
      ABCB1b and ABCG2, were up-regulated after alpha-tocopherol injections, whereas
      OATP, a liver influx transporter, was down-regulated. Thus, an overload of
      hepatic alpha-tocopherol increases its own metabolism and increases expression of
      genes of transporters that are postulated to lead to increased excretion of both
      vitamin E and its metabolites.

PMID- 21945368
TI  - Hyperosmolality in the plasma modulates behavioral thermoregulation in mice: the
      quantitative and multilateral assessment using a new experimental system.
AB  - We evaluated the effect of plasma hyperosmolality on behavioral thermoregulation
      in mice, using a new experimental system. The system consisted of Plexiglas box
      (dimensions: 50*12*19 cm) with five computer-controlled Peltier boards
      (dimensions: 10*10 cm) at the bottom. Experiments were conducted in two different
      settings of the system. An operant behavior setting: each board was first set to
      39 degrees C, and the right-end board was changed to 20 degrees C for 1 min when
      a mouse moved to a specific position. A temperature mosaic setting: each board
      was randomly set to 15 degrees C, 22 degrees C, 28 degrees C, 35 degrees C, or 39
      degrees C with a 6-min interval, but each board temperature was different from
      the others at a given time point. Mice were injected subcutaneous (s.c.) isotonic
      or hypertonic saline (154 mM (IS group) or 2,500 mM (HS group), 10 ml/kg body
      wt), and exposed to either setting for 90 min. In the operant setting, the HS
      group showed fewer operant behavior counts than the IS group (11+/-5 and 25+/-4
      counts, respectively; P<0.05) with greater increase in body temperature (1.6+/
      0.4 degrees C vs. 0.0+/-0.2 degrees C, respectively; P<0.05). In the mosaic
      setting, the HS group selected the board temperature of 35 degrees C more
      frequently than the other temperatures (P<0.05) with the same increase in body
      temperature. These results may suggest that plasma hyperosmolality modulates
      behavioral thermoregulatory response to heat and induce regulated hyperthermia.

PMID- 21945369
TI  - Stress affects salivary alpha-Amylase activity in bonobos.
AB  - Salivary alpha-Amylase (sAA) is a starch digesting enzyme. In addition to its
      function in the context of nutrition, sAA has also turned out to be useful for
      monitoring sympathetic nervous system activity. Recent studies on humans have
      found a relationship between intra-individual changes in sAA activity and
      physical and psychological stress. In studies on primates and other vertebrates,
      non-invasive monitoring of short-term stress responses is usually based on
      measurements of cortisol levels, which are indicative of hypothalamic-pituitary
      adrenal activity. The few studies that have used both cortisol levels and sAA
      activity indicate that these two markers may respond differently and
      independently to different types of stress such that variation in the degree of
      the activation of different stress response systems might reflect alternative
      coping mechanisms or individual traits. Here, we present the first data on intra-
      and inter-individual variation of sAA activity in captive bonobos and compare the
      results with information from other ape species and humans. Our results indicate
      that sAA activity in the bonobo samples was significantly lower than in the human
      samples but within the range of other great ape species. In addition, sAA
      activity was significantly higher in samples collected at times when subjects had
      been exposed to stressors (judged by changes in behavioral patterns and cortisol
      levels) than in samples collected at other times. Our results indicate that
      bonobos possess functioning sAA and, as in other species, sAA activity is
      influenced by autonomic nervous system activity. Monitoring sAA activity could
      therefore be a useful tool for evaluating stress in bonobos.

PMID- 21945370
TI  - Simultaneous measurement of endogenous steroid hormones and their metabolites
      with LC-MS/MS in faeces of a New World primate species, Cebus capucinus.
AB  - We developed and validated a method to measure steroid hormones with liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) in faecal samples of white
      faced capuchins. The method includes the measurement of adrenal and gonadal
      hormones such as cortisol, testosterone, estrone, progesterone and a number of
      their faecal metabolites. This method can be used for simultaneous routine
      measurements of steroids in faecal samples and provides a reference method for
      the validation of new immunoassays in this matrix. The optimised method consists
      of an extraction of the dried faecal samples with 80% methanol followed by
      purification of the extracts by solid phase extraction, solvolytic cleavage of
      conjugates and liquid-liquid extraction. Extracts were measured by LC-MS/MS with
      an electrospray interface in positive ionisation mode. Out of 19 steroids spiked
      into methanol extracts, 14 showed a recovery of 79.8-118.5% with an intra-day
      precision of 2.5-13.0% and an inter-day precision of 7.2-15.1%. Detection limits
      for these steroids ranged from 0.3 to 27.0 ng/mL of extract. Five steroids did
      not fulfil our requirements concerning precision and accuracy and we therefore
      considered these to not be reliably measurable with this method. While there was
      no indication of considerable amounts of conjugated forms for most metabolites,
      87% of the testosterone was found in the solvolysis fraction, which indicates
      that the majority of testosterone was conjugated. Therefore, solvolysis turned
      out to be crucial, especially for the quantification of the total amount of
      testosterone. The physiological validation of this LC-MS/MS method confirmed
      known physiologically caused differences in faecal steroid concentrations. This
      indicates the usefulness of the method in investigating variation in the levels
      of major steroid hormones in faeces of white-faced capuchins. The possibility to
      simultaneously measure hormones of the hypothalamic-pituitary-adrenal (HPA) axis
      and the hypothalamic-pituitary-gonadal (HPG) axis makes this method suitable for
      dealing with questions concerning the cross talk between those axes.

PMID- 21945371
TI  - The effect of escapable versus inescapable social defeat on conditioned defeat
      and social recognition in Syrian hamsters.
AB  - Male Syrian hamsters are naturally aggressive animals that reliably defend their
      home territory against intruding conspecifics. Hamsters that lose agonistic
      encounters subsequently exhibit a striking change in their agonistic behavior,
      however, expressing no aggression and instead becoming highly submissive, a
      behavioral change that we have termed conditioned defeat. We have generally
      employed an inescapable defeat training protocol when studying conditioned
      defeat. The purpose of the present study was to determine if conditioned defeat
      is an epiphenomenon of the inescapable defeat experience by comparing the
      behavior of hamsters exposed to inescapable versus escapable defeat. In the
      conditioned defeat model, defeated hamsters subsequently generalize their
      submission and social avoidance to a novel, non-aggressive opponent, suggesting
      that hamsters subjected to inescapable defeat may not form a specific memory of
      their aggressive opponent. Thus, a secondary purpose of the present study was to
      determine whether hamsters subjected to our defeat protocol have the ability to
      recognize a familiar opponent following defeat. Our results provide evidence that
      conditioned defeat is not solely a by-product of inescapable defeat because all
      experimental animals, regardless of the type of defeat, expressed conditioned
      defeat during testing. We also found that animals experiencing an inescapable
      defeat avoided a familiar aggressor significantly more than they did an
      unfamiliar aggressor, demonstrating that these animals have the ability to
      recognize their previous attacker. Thus, we maintain that a variety of social
      defeat models, and conditioned defeat in particular, represent generalizable and
      ethologically valid models with which to study the effects of social stress on
      physiology and behavior.

PMID- 21945372
TI  - Post-fasting olfactory, transcriptional, and feeding responses in Drosophila.
AB  - The sensation of hunger after a period of fasting and of satiety after eating is
      crucial to behavioral regulation of food intake, but the biological mechanisms
      regulating these sensations are incompletely understood. We studied the
      behavioral and physiological adaptations to fasting in the vinegar fly
      (Drosophila melanogaster). Here we show that both male and female flies increased
      their rate of food intake transiently in the post-fasted state. Although the
      basal feeding rate was higher in females than males, the magnitude of the post
      fasting feeding response was the same in both sexes. Flies returned to a stable
      baseline feeding rate within 12 h after return to food for males and 24 h for
      females. This modulation in feeding was accompanied by a significant increase in
      the size of the crop organ of the digestive system, suggesting that fasted flies
      responded both by increasing their food intake and storing reserve food in their
      crop. Flies demonstrated increased behavioral attraction to an attractive odor
      when food-deprived. Expression profiling of head, body, and chemosensory tissues
      by microarray analysis revealed 415 genes regulated by fasting after 24 h and 723
      genes after 48 h, with downregulated genes outnumbering upregulated genes in each
      tissue and fasting time point. These transcriptional changes showed rich temporal
      dynamics and affected genes across multiple functional gene ontology categories.
      These observations suggest that a coordinated transcriptional response to
      internal physiological state may regulate both ingestive behaviors and
      chemosensory perception of food.

PMID- 21945374
TI  - Solubilization and folding of a fully active recombinant Gaussia luciferase with
      native disulfide bonds by using a SEP-Tag.
AB  - Gaussia luciferase (GLuc) is the smallest known bioluminescent protein and is
      attracting much attention as a potential reporter protein. However, its 10
      disulfide bond forming cysteines have hampered the efficient production of
      recombinant GLuc and thus limited its use in bio-imaging application. Here, we
      demonstrate that the addition of a short solubility enhancement peptide tag (SEP
      Tag) to the C-terminus of GLuc (GLuc-C9D) significantly increased the fraction of
      soluble protein at a standard expression temperature. The expression time was
      much shorter, and the final yield of GLuc-C9D was significantly higher than with
      our previous pCold expression system. Reversed phase HPLC indicated that the GLuc
      C9D variant folded with a single disulfide bond pattern after proper oxidization.
      Further, the thermal denaturation of GLuc-C9D was completely reversible, and its
      secondary structure content remained unchanged until 40 degrees C as assessed by
      CD spectroscopy. The (1)H-NMR spectrum of GLuc indicated sharp well dispersed
      peaks typical for natively folded proteins. GLuc-C9D bioluminescence activity was
      strong and fully retained even after incubation at high temperatures. These
      results suggest that solubilization using SEP-Tags can be useful for producing
      large quantities of proteins containing multiple disulfide bonds.

PMID- 21945375
TI  - Insight into the binding of the wild type and mutated alginate lyase (AlyVI) with
      its substrate: a computational and experimental study.
AB  - The homology model of the wild type alginate lyase (AlyVI) marine bacterium
      Vibrio sp. protein, was built using the crystal structure of the Family 7
      alginate lyase from Sphingomonas sp. A1. To rationalize the observed structure
      affinity relationships of aliginate lyase alyVI with its (GGG) substrate,
      molecular docking, MD imulations and binding free energy calculations followed by
      site-directed mutagenesis and alyVI activity assays were carried out. Per-residue
      decomposition of the (GGG) binding energy revealed that the most important
      contributions were from polar and charged residues, such as Asn138, Arg143,
      Asn217, and Lys308, while van der Waals interactions were responsible for binding
      with the catalytic His200 and Tyr312 residues. The mutants H200A, K308A, Y312A,
      Y312F, and W165A were found to be inactive or almost inactive. However, the
      catalytic efficiency (k(cat)/K(m)) of the double mutant L224V/D226G increased by
      two-fold compared to the wild type enzyme. This first structural model with its
      substrate binding mode and the agreement with experimental results provide a
      suitable base for the future rational design of new mutated alyVI structures with
      improved catalytic activity.

PMID- 21945373
TI  - Strain differences in sucrose- and fructose-conditioned flavor preferences in
      mice.
AB  - Genetic factors strongly influence the intake and preference for sugar and
      saccharin solutions in inbred mouse strains. The present study determined if
      genetic variance also influences the learned preferences for flavors added to
      sugar solutions. Conditioned flavor preferences (CFPs) are produced in rodents by
      adding a flavor (CS+) to a sugar solution and a different flavor (CS-) to a
      saccharin solution (CS-) in one-bottle training trials; the CS+ is subsequently
      preferred to the CS- when both are presented in saccharin solutions in two-bottle
      tests. With some sugars (e.g., sucrose), flavor preferences are reinforced by
      both sweet taste and post-oral nutrient effects, whereas with other sugars (e.g.,
      fructose), sweet taste is the primary reinforcer. Sucrose and fructose were used
      in three experiments to condition flavor preferences in one outbred (CD-1) and
      eight inbred strains which have "sensitive" (SWR/J, SJL/J, C57BL/10J, C57BL/6J)
      or "sub-sensitive" (DBA/2J, BALB/cJ, C3H/HeJ, 129P3/J) sweet taste receptors
      (T1R2/T1R3). Food-restricted mice of each strain were trained (1 h/day) to drink
      flavored 16% sucrose (CS+ 16S, Experiment 1), 16% fructose (CS+ 16F, Experiment
      2) or 8% fructose+0.2% saccharin (CS+ 8F, Experiment 3) solutions on five
      alternate days and a differently flavored saccharin solution (0.05% or 0.2%, CS-)
      on the other five alternating days. The CS+ and CS- flavors were presented in
      0.2% saccharin for two-bottle testing over six days. All strains preferred the
      CS+ 16S to CS- although there were significant strain differences in the
      magnitude and persistence of the sucrose preference. The strains also differed in
      the magnitude and persistence of preferences for the CS+ 16F and CS+ 8F flavors
      over the CS- with two strains failing to prefer the fructose-paired flavors.
      Sucrose conditioned stronger preferences than did fructose which is attributed to
      differences in the taste and post-oral actions of the sugars. These differential
      training intakes may not have influenced the sucrose-CFP because of the post-oral
      reinforcing actions of sucrose. Overall, sweet sensitive and sub-sensitive mice
      did not differ in sucrose-CFP, but unexpectedly, the sub-sensitive mice displayed
      stronger fructose-CFP. This may be related to differential training intakes of
      CS+ and CS- solutions: sweet sensitive mice consumed more CS- than CS+ during
      training while sub-sensitive mice consumed more CS+.

PMID- 21945376
TI  - In-situ confocal Raman observation of structural changes of insulin crystals in
      sequential dehydration process.
AB  - In-situ confocal Raman spectroscopy combined with relative humidity (RH) control
      technique was used to study the sequential dehydration process of insulin
      crystals. By gradually decreasing the ambient RH of the insulin crystal, the
      content of the hydration water in the crystal was quantitatively controlled.
      Tyrosine (Tyr) residues were very sensitive to the micro-environmental changes,
      and four Raman features 828cm(-1), 852cm(-1), 1174cm(-1) and 1206cm(-1) of Tyr
      were employed to monitor the dehydration process. Taking advantage of the ratios
      I(852)/I(828) at different RH values, the mole fractions of the 'exposed' and
      'buried' Tyr residues were estimated. Moreover, using the ratio I(1174)/I(1206)
      as an indicator of the dehydration process, three RH regions were discriminated.
      This is believed to imply that different types of the hydration water were lost
      step by step, i.e. firstly the 'second-layer' and 'first-layer' classes, then the
      'contact' class, and finally, the 'inside' class. In addition, the profile of the
      amide I band was observed to gradually change with RH. By band fitting of the
      amide I region, changes in secondary structure were quantitatively determined.
      And the results showed that nearly 17% of alpha-helix converted into beta-sheet
      with RH decreasing from 92% to 2%.

PMID- 21945377
TI  - Accruing the sample: strategies for recruiting older adult and African Americans
      caregivers for persons with Alzheimer's disease.
AB  - The challenges and barriers associated with recruiting a representative sample of
      community-residing older adult caregivers for persons with Alzheimer's disease
      (AD) may limit efficient accrual in a reasonable period. These limitations may
      inhibit study completion, result in underpowered samples, or overextend research
      budgets. With the use of both grassroots recruiting and local community
      resources, successful recruitment methods and experiences obtained during two
      studies, the first in older adults caring for a spouse with AD and the second in
      family caregivers for African Americans with AD, are described. Strategies used
      to accrue the samples are discussed within the framework of knowledge, planning,
      and creativity.

PMID- 21945378
TI  - Designing an intervention: therapeutic showering in labor.
AB  - Therapeutic showering is a nonpharmacologic comfort measure used during labor but
      is not tested empirically. The purpose of this article was to report the
      systematic development of therapeutic showering during labor using best available
      evidence so that nurses in practice and research can further test and refine this
      nursing intervention.

PMID- 21945379
TI  - Impaired functioning in euthymic patients with bipolar disorder--HSV-1 as a
      predictor.
AB  - There is a possible association between infectious agents and psychiatric
      disorders. Previous studies in the US provided evidence for cognitive impairment
      correlated with Herpes simplex virus type 1 (HSV-1) infection. For a replication
      study in Europe we chosed individuals diagnosed with bipolar disorder to analyse
      the correlation with HSV-1 infection. Antibody prevalence was analyzed by using
      solid phase immunoassay techniques. Cognitive functioning was tested with the
      Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Form
      A, the Trail Making Test A&B, and two subtests from the WAIS III: the Letter
      Number Sequencing Task and the subtest on information. History and
      psychopathology was assessed using structured interviews and validated rating
      scales (SCID, HRSD-21, YMRS, PANSS). Additionally, we investigated social
      functioning and quality of life using self-assessment-scales (SAS, LQLP).
      Prevalence rates of antibodies against diverse infectious agents did not differ
      significantly between patients and controls. We found a significant correlation
      between cognitive impairment in patients with bipolar disorder and the prevalence
      of antibodies directed against HSV-1. Cognitive functions were significantly
      impaired including language, attention, and immediate memory. The results of this
      study confirm previous findings suggesting that HSV-1 affects cognitive functions
      in patients with bipolar disorder. This may also result in more impaired
      functioning, less quality of life and difficulties in social adjustment.

PMID- 21945380
TI  - Time delay in physiological systems: analyzing and modeling its impact.
AB  - This article examines the functional and clinical impact of time delays that
      arise in human physiological systems, especially control systems. An overview of
      the mathematical and physiological contexts for considering time delays will be
      illustrated, from the system level to cell level, by examining models that
      incorporate time delays. This examination will highlight how such delays in
      combination with other system structures and parameters influence system
      dynamics. Model analysis that reveals the influence of delays can also reveal
      related physiological effects which may have medical consequences and clinical
      applications.

PMID- 21945381
TI  - Stochastic models for virus and immune system dynamics.
AB  - New stochastic models are developed for the dynamics of a viral infection and an
      immune response during the early stages of infection. The stochastic models are
      derived based on the dynamics of deterministic models. The simplest deterministic
      model is a well-known system of ordinary differential equations which consists of
      three populations: uninfected cells, actively infected cells, and virus
      particles. This basic model is extended to include some factors of the immune
      response related to Human Immunodeficiency Virus-1 (HIV-1) infection. For the
      deterministic models, the basic reproduction number, R0, is calculated and it is
      shown that if R0<1, the disease-free equilibrium is locally asymptotically stable
      and is globally asymptotically stable in some special cases. The new stochastic
      models are systems of stochastic differential equations (SDEs) and continuous
      time Markov chain (CTMC) models that account for the variability in cellular
      reproduction and death, the infection process, the immune system activation, and
      viral reproduction. Two viral release strategies are considered: budding and
      bursting. The CTMC model is used to estimate the probability of virus extinction
      during the early stages of infection. Numerical simulations are carried out using
      parameter values applicable to HIV-1 dynamics. The stochastic models provide new
      insights, distinct from the basic deterministic models. For the case R0>1, the
      deterministic models predict the viral infection persists in the host. But for
      the stochastic models, there is a positive probability of viral extinction. It is
      shown that the probability of a successful invasion depends on the initial viral
      dose, whether the immune system is activated, and whether the release strategy is
      bursting or budding.

PMID- 21945382
TI  - A dual-wavelength overlapping resonance Rayleigh scattering method for the
      determination of chondroitin sulfate with nile blue sulfate.
AB  - A dual-wavelength overlapping resonance Rayleigh scattering (DWO-RRS) method was
      developed to detect chondroitin sulfate (CS) with nile blue sulfate (NBS). At pH
      3.0-4.0 Britton-Robinson (BR) buffer medium, CS interacted with NBS to form an
      ion-association complex. As a result, the new spectra of resonance Rayleigh
      scattering (RRS), second order scattering (SOS) and frequence doubling scattering
      (FDS) appeared and their intensities were enhanced greatly. Their maximum
      wavelengths were located at 303 nm (RRS), 362 nm (RRS), 588 nm (SOS) and 350 nm
      (FDS), respectively. The scattering intensities of the three methods were
      proportional to the concentration of CS in certain ranges. The methods had high
      sensitivity and the detection limits were between 1.5 and 7.1 ng mL(-1). The DWO
      RRS method had the highest sensitivity with the detection limit being 1.5 ng mL(
      1). The characteristics of the spectra and optimal reaction conditions of RRS
      method were investigated. The effects of coexistent substances on the
      determination of CS were evaluated. Owing to the high sensitivity, RRS method had
      been applied to the determination of CS in eye drops with satisfactory results.
      The recovery range was between 99.4% and 104.6% and the relative standard
      deviation (RSD) was between 0.4% and 0.8%. In addition, the reasons for RRS
      enhancement were discussed and the shape of ion-association complex was
      characterized by atomic force microscopy (AFM).

PMID- 21945383
TI  - NMR and conformational studies of linear and cyclic oligo-(1->6)-beta-D
      glucosamines.
AB  - The conformational behavior of a series of linear and cyclic oligo-(1->6)-beta-D
      glucosamines and their N-acetylated derivatives, which are related to fragments
      of natural poly-N-acetylglucosamine, was studied by theoretical molecular
      modeling and experimental determination of transglycosidic vicinal coupling
      constants (3)J(C,H) and (3)J(H,H). Molecular dynamics simulations were performed
      under several types of conditions varying in the consideration of ionization of
      amino groups, solvent effect, and temperature. Neural network clustering and
      asphericity calculations were performed on the basis of molecular dynamics data.
      It was shown that disaccharide fragments in the studied linear oligosaccharides
      were not rigid, and tended to have several conformers, thus determining the
      overall twisted shape with helical elements. In addition, it was found that the
      behavior of C5-C6 bond depended significantly upon the simulation conditions. The
      cyclic di-, tri-, and tetrasaccharides mostly had symmetrical ring-shaped
      conformations. The larger cycles tended to adopt more complicated shapes, and the
      conformational behavior of their disaccharide fragments was close to that in the
      linear oligosaccharides.

PMID- 21945384
TI  - Regioselective allylation of cyclomaltoheptaose (beta-cyclodextrin) leading to
      per(2,6-di-O-hydroxypropyl-3-O-methyl)-beta-cyclodextrin.
AB  - The selective modification of cyclodextrins remains a real challenge to obtain
      well-defined structures. The targeted cycloheptakis-(1->4)-2,6-di-O-hydroxypropyl
      3-O-methyl-alpha-D-glucopyranosyl [per(2,6-di-O-hydroxypropyl-3-O-methyl)-beta
      CD] was obtained by a three-step procedure. The selective allylation of the
      hydroxyl functions at the positions 2 and 6 was used as a first step. This
      reaction was revisited then enlarged to alpha and gamma-CDs to determine new
      conditions for a one-step synthesis in high yield. The per(2,6-di-O-allyl)-beta
      CD derivative was then reacted with iodomethane to provide per(2,6-di-O-allyl-3-O
      methyl)-beta-CD. Oxidative hydroboration of the allyl functions was then carried
      out in order to obtain a new CD derivative with seven primary hydroxyl functions
      on each side of the truncated cone, having a similar reactivity.

PMID- 21945385
TI  - Fixed-bearing unicompartmental knee arthroplasty. Patients' selection and
      operative technique.
AB  - Unicompartmental knee arthroplasty (UKA) is designed for patients presenting
      arthritic wear limited to a single medial or lateral tibiofemoral compartment.
      The indication is based on strict criteria. Wear must stem from degenerative
      osteoarthritis or be secondary to aseptic necrosis of the medial condyle.
      Inflammatory rheumatism is a contraindication. Age and activity level should be
      compatible with an indication for arthroplasty. The body mass index should be
      less than 30 kg/m(2). The ligament system must be intact, particularly both
      cruciate ligaments. Any pre-existing axis deformity should be moderate and the
      residual axis deformity, after correction of wear with a unicompartmental tibial
      augmentation spacer, should not exceed 7-10 degrees  varus or valgus. These
      highly restrictive conditions result in the ideal indications for UKA suitable
      for no more than 15-20% of knee arthroplasty candidates for most surgeons
      experienced in this procedure. Although the results of certain early series
      worried potential users, today it can be asserted that recent series whose
      indications and technique correspond to modern use criteria, have shown results
      that are as reliable as those of total knee arthroplasty (TKA) at a 10 years'
      follow-up. Beyond this time frame, the risk of polyethylene wear related to the
      technical restrictions of the UKA is another consideration. Indeed, to prevent
      the risk of rapid extension of osteoarthritis to the opposite compartment, the
      procedure should be limited to restoring the patient's constitutional axis before
      wear phenomena had set in. This makes UKA a surgical procedure at risk of failure
      due to wear phenomena. Much of this paper will describe the precise rules for UKA
      positioning, which are critical to observe to warrant these implants outcome and
      longevity.

PMID- 21945386
TI  - Accuracy of the actibelt((r)) accelerometer for measuring walking speed in a
      controlled environment among persons with multiple sclerosis.
AB  - BACKGROUND: Advances in portable sensor technology have opened an era for
      objective, real-life monitoring of walking speed in persons with multiple
      sclerosis (MS). PURPOSE: The present study examined the accuracy of the
      actibelt((r)) accelerometer for measuring walking speed during a standard 6-min
      walk (6MW) and the possibility that disability status influenced the degree of
      accuracy among persons with MS. METHODS: On a single testing session, 51 persons
      with MS and Expanded Disability Status Scale scores between 2.0 and 6.5 performed
      a 6MW while wearing an actibelt((r)) in the body's sagittal symmetry plane and
      close to the body's centre of mass. RESULTS: All 51 participants completed the
      6MW without stopping, falling, or any adverse events, and the actibelt((r))
      provided walking speed data for each of the participants. The actibelt((r))
      significantly overestimated walking speed (actual minus actibelt((r))) by a
      mean+/-standard deviation of -0.12+/-0.17 m/s for the overall sample (p<0.0001).
      There was no significant overestimation in the sample with mild disability (
      0.02+/-0.11 m/s), but there was in the samples with moderate (-0.10+/-0.16 m/s)
      and severe (-0.26+/-0.12 m/s) disability. CONCLUSION: The actibelt((r)) is ready
      for real-life monitoring of walking speed in persons with mild MS, but caution is
      necessary when interpreting the accuracy of the walking speed data for those with
      MS who have moderate and severe disability.

PMID- 21945387
TI  - Early brain recurrences are potentially detectable in asymptomatic, early stage
      lung adenocarcinoma.

PMID- 21945388
TI  - Innovations in continuing professional development--countering the Dunning-Kruger
      effect.

PMID- 21945389
TI  - Brain-derived neurotrophic factor, food intake regulation, and obesity.
AB  - Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a
      fundamental role in development and plasticity of the central nervous system
      (CNS). It is currently recognized as a major participant in the regulation of
      food intake. Multiple studies have shown that different regulators of appetite
      such as leptin, insulin and pancreatic polypeptide (PP) potentially exert
      anorexigenic effects through BDNF. Low circulating levels of BDNF are associated
      with a higher risk of eating disorders such as anorexia nervosa (AN) and bulimia
      nervosa (BN). Strict food restriction reduces BDNF and may trigger binge-eating
      episodes and weight gain. The existence of mutations that cause
      haploinsufficiency of BDNF as well as some genetic variants, notably the BDNF
      p.Val66Met polymorphism, are also associated with the development of obese
      phenotypes and hyperphagia. However, association of the Met allele with AN and
      BN, which have different phenotypic characteristics, shows clearly the existence
      of other relevant factors that regulate eating behavior. This may, in part, be
      explained by the epigenetic regulation of BDNF through mechanisms like DNA
      methylation and histone acetylation. Environmental factors, primarily during
      early development, are crucial to the establishment of these stable but
      reversible changes that alter the transcriptional expression and are
      transgenerationally heritable, with potential concomitant effects on the
      development of eating disorders and body weight control.

PMID- 21945390
TI  - Mycobacterium wolinskyi: a case series and review of the literature.
AB  - Mycobacterium wolinskyi is an uncommonly encountered rapidly growing
      mycobacterium. To date, only 12 clinical cases have been reported in the
      literature. In this report, we describe 5 additional cases of M. wolinskyi
      infection seen at the Mayo Clinic in Rochester, MN, since 2009. The clinical
      manifestations were sternal wound infections (n = 2), a surgical site wound
      infection, a cardiac-device pocket site infection, and a vascular graft infection
      with bacteremia. The infections occurred in both immunocompetent and
      immunosuppressed patients, including a lung transplant recipient. Treatment of M.
      wolinskyi infections required a prolonged course of combination antimicrobial
      treatment and surgical debridement.

PMID- 21945391
TI  - Susceptibility testing of terbinafine alone and in combination with amphotericin
      B, itraconazole, or voriconazole against conidia and hyphae of dematiaceous
      molds.
AB  - Studies have demonstrated excellent in vivo efficacy of terbinafine combined with
      other antifungal agents against dematiaceous molds; however, there is a lack of
      in vitro studies. Most studies evaluated conidia inocula, but susceptibility
      testing of hyphae could mimic the fungal status in infected tissues and might
      reflect the therapeutic potential of the agent. We investigated the in vitro
      susceptibility of terbinafine alone and in combination with amphotericin B,
      itraconazole, or voriconazole against conidia by microdilution and dynamic
      measurement of hyphae growth of dematiaceous molds. The MIC values for hyphae
      were, until 3 dilutions, below the MIC obtained for conidia. The results
      indicated 100% synergistic interactions between terbinafine and azoles or
      amphotericin B in all tests, but lower MICs for hyphae. In conclusion, our
      findings allow us to say that the hyphal form of tested dematiaceous molds showed
      high susceptibility to all antifungal agents evaluated, alone and in combination
      with terbinafine.

PMID- 21945392
TI  - A neurally plausible parallel distributed processing model of event-related
      potential word reading data.
AB  - The Parallel Distributed Processing (PDP) framework has significant potential for
      producing models of cognitive tasks that approximate how the brain performs the
      same tasks. To date, however, there has been relatively little contact between
      PDP modeling and data from cognitive neuroscience. In an attempt to advance the
      relationship between explicit, computational models and physiological data
      collected during the performance of cognitive tasks, we developed a PDP model of
      visual word recognition which simulates key results from the ERP reading
      literature, while simultaneously being able to successfully perform lexical
      decision-a benchmark task for reading models. Simulations reveal that the model's
      success depends on the implementation of several neurally plausible features in
      its architecture which are sufficiently domain-general to be relevant to
      cognitive modeling more generally.

PMID- 21945393
TI  - Wild type and P301L mutant Tau promote neuro-inflammation and alpha-Synuclein
      accumulation in lentiviral gene delivery models.
AB  - Neurodegeneration involves multiple pathogenic proteins, including Tau, Abeta,
      TDP-43 and alpha-Synuclein, but there is little information how these pathogenic
      proteins interact. We cloned human wild type 4 repeat Tau (Tau(wt)) and mutant
      Tau(P301L) into a lentivirus and performed stereotaxic injection into the rat
      motor cortex to examine Tau modification, neuro-inflammation and changes of other
      proteins associated with neurodegeneration. Tau(P301L) was associated with more
      phosphorylation of Tau, including Thr 181 and Ser 262 residues and resulted in
      more aggregation. Both forms of Tau expression increased glycogen synthase kinase
      3 (GSK-3) activity, polo-like kinase-2 (PLK2) levels and decreased protein
      phosphatase activity, but had no effects on casein kinase-1 (CK1). No changes
      were observed in glial fibrillary acidic protein (GFAP) staining with either
      Tau(wt) or Tau(P301L), but both caused microglial changes and higher interleukin
      6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) levels. Tau(wt) and
      Tau(P301L) increased the levels of endogenous alpha-Synuclein, but not beta
      amyloid precursor protein (betaAPP) or Tar-DNA binding protein (TDP-43). The
      levels of phosphorylated Ser-129 alpha-Synuclein (p-Ser129) were also increased
      with Tau(wt) and Tau(P301L) expressing animals. These data suggest that Tau(wt)
      and Tau(P301L) alter kinase activities, but they differentially induce
      inflammation, Tau modification and alpha-Synuclein phosphorylation. This change
      of alpha-Synuclein in Tau gene transfer models suggests that Tau pathology may
      lead to alpha-Synuclein modification in neurodegenerative diseases.

PMID- 21945394
TI  - A quantitative proteomic approach for detecting protein profiles of activated
      human myeloid dendritic cells.
AB  - Dendritic cells (DC) direct the magnitude, polarity and effector function of the
      adaptive immune response. DC express toll-like receptors (TLR), antigen capturing
      and processing machinery, and costimulatory molecules, which facilitate innate
      sensing and T cell activation. Once activated, DC can efficiently migrate to
      lymphoid tissue and prime T cell responses. Therefore, DC play an integral role
      as mediators of the immune response to multiple pathogens. Elucidating the
      molecular mechanisms involved in DC activation is therefore central in gaining an
      understanding of host response to infection. Unfortunately, technical constraints
      have limited system-wide 'omic' analysis of human DC subsets collected ex vivo.
      Here we have applied novel proteomic approaches to human myeloid dendritic cells
      (mDCs) purified from 100 mL of peripheral blood to characterize specific
      molecular networks of cell activation at the individual patient level, and have
      successfully quantified over 700 proteins from individual samples containing as
      little as 200,000 mDCs. The proteomic and network readouts after ex vivo
      stimulation of mDCs with TLR3 agonists are measured and verified using flow
      cytometry.

PMID- 21945395
TI  - Ultra-sensitive detection of rare T cell clones.
AB  - Advances in high-throughput sequencing have enabled technologies that probe the
      adaptive immune system with unprecedented depth. We have developed a multiplex
      PCR method to sequence tens of millions of T cell receptors (TCRs) from a single
      sample in a few days. A method is presented to test the precision, accuracy, and
      sensitivity of this assay. T cell clones, each with one fixed productive TCR
      rearrangement, are doped into complex blood cell samples. TCRs from a total of
      eleven samples are sequenced, with the doped T cell clones ranging from 10% of
      the total sample to 0.001% (one cell in 100,000). The assay is able to detect
      even the rarest clones. The precision of the assay is demonstrated across five
      orders of magnitude. The accuracy for each clone is within an overall factor of
      three across the 100,000 fold dynamic range. Additionally, the assay is shown to
      be highly repeatable.

PMID- 21945396
TI  - Effect of IL-15 on IgG versus IgE antibody-secreting cells in vitro.
AB  - Immunoglobulin E (IgE) antibodies are major contributors to the pathology of
      atopic and allergic diseases as well as to immune response to helminth
      infections. Development of an adequate immunoglobulin G (IgG) immune response
      against infectious agents and vaccine antigens is considered in most cases as
      crucial for protection from disease. In vivo and in vitro production of IgE and
      IgG depends on cytokines and other soluble factors. Recently it has been shown
      that IgG antibody secreting cells (ASCs) can be generated by in vitro maturation
      of blood cells with Interleukin- (IL-)15 and CpG DNA or other stimulation
      cocktails, while IgE-ASCs develop upon cultivation with anti-CD40 and IL-4. In
      the present study we employed an enzyme linked immunospot assay (ELISPOT) to
      assess the capacity of individuals to develop into either IgE-ASCs or IgG-ASCs
      upon stimulation with different combinations of stimulation cocktails in order to
      investigate the influence of cytokines that are dysregulated in IgE-mediated
      immune reactions on ASC generation. Furthermore, we modified the method to assess
      IgG- and IgE-ASCs specific for two model antigens causing allergic rhinitis in
      humans. We demonstrate that IL-15, which is important for development of IgG
      ASCs, decreases the number of IgE-ASCs when added to media commonly used for in
      vitro development of IgE-ASCs. We show that our method is suitable for the
      detection of specific and non-specific IgE-ASCs and IgG-ASCs and allows the
      investigation of the interplay between IgG-ASCs and IgE-ASCs in different
      populations.

PMID- 21945397
TI  - Alternative mechanism for anti-obesity effect of dehydroepiandrosterone: possible
      contribution of 11beta-hydroxysteroid dehydrogenase type 1 inhibition in rodent
      adipose tissue.
AB  - Dehydroepiandrosterone (DHEA) has been suggested to have an anti-obesity effect;
      however, the mechanism underlying this effect remains unclear. The effect of DHEA
      on adipocytes opposes that of glucocorticoids, which potentiate adipogenesis. The
      key to the intracellular activation of glucocorticoids in adipocytes is 11beta
      hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which catalyses the production
      of active glucocorticoids (cortisol in humans and corticosterone in rodents) from
      an inactive 11-keto form (cortisone in humans and 11-dehydrocorticosterone in
      rodents). In humans and rodents, intracellular glucocorticoid reactivation is
      exaggerated in obese adipose tissue. Using differentiated 3T3-L1 adipocytes, we
      demonstrated that DHEA inhibited about 15.6% of 11beta-HSD1 activity at a
      concentration of 1 MUM within 10min. Inhibition was also observed in a cell-free
      system composed of microsomes prepared from rat adipose tissue and NADPH, a
      coenzyme of 11beta-HSD1. A kinetic study revealed that DHEA acted as a non
      competitive inhibitor of 11beta-HSD1. Moreover, conversion from DHEA to estrogens
      was not observed by sensitive semi-micro HPLC equipped with electrochemical
      detector. These results indicate that the inhibition of 11beta-HSD1 by DHEA
      depends on neither the transcriptional pathway nor the nonspecific manner. This
      is the first demonstration that the anti-obesity effect of DHEA is exerted by non
      transcriptional inhibition of 11beta-HSD1 in rodent adipocytes.

PMID- 21945398
TI  - Diverse immunostaining patterns of mineralocorticoid receptor monoclonal
      antibodies.
AB  - The mineralocorticoid receptor (MR) is a widely distributed ligand activated
      nuclear transcription factor that is bound by various chaperone proteins that
      alter its conformation depending upon its location in the cell and whether it is
      ligand-bound. We describe the development and characterization of new monoclonal
      antibodies produced against a rat recombinant protein corresponding to aminoacids
      5-550 of the MR to produce antibodies that recognize the receptor in specific
      conformations. Most of the resulting monoclonal antibodies studied were similar
      to those we produced by immunization with peptide isotopes, however two detected
      a single band at the appropriate molecular mass as the MR and had distinct
      immunostaining characteristics in neurons. One labeled cytosolic MR, the other
      labeled membranes and cytosol, including axons. These antibodies will permit
      study of the subcellular localization of the MR under various physiological and
      pathological conditions. We have also confirmed that the MR is highly unstable
      and requires special handling.

PMID- 21945399
TI  - Tibiotalocalcaneal arthrodesis using a femoral locking plate.
AB  - The goal of a tibiotalocalcaneal arthrodesis is to create a pain-free, stable
      hindfoot and ankle. Although a reserved procedure, it is useful when simultaneous
      ankle and subtalar joint pathology exists. Numerous complications have been
      reported after tibiotalocalcaneal arthrodesis, most importantly nonunion. Locking
      plates have proved to be a more stable construct than alternative forms of
      arthrodesis. In the inverted positions, the hybrid plating of the femoral locking
      plate structurally aligns with the anatomy of the hindfoot. This provides an
      anatomically sound construct, while allowing for both locking and lag screw
      insertion. We describe a new technique using a 4.5-mm condylar plate for
      tibiotalocalcaneal arthrodesis.

PMID- 21945400
TI  - Reconstruction of large defect of foot with extensive bone loss exclusively using
      a latissimus dorsi muscle free flap: a potential new indication for this flap.
AB  - In cases of extensive damage to the foot, with significant bone loss, it is
      generally accepted that reconstruction must include bone flaps or grafts either
      in the emergency setting or subsequently. In this report, we describe the case of
      an 18-year-old student with an avulsion injury of the dorsum of his right foot.
      Consequently, he lost most of the soft tissue over the dorsum of the foot and the
      cuboid, navicular, and cuneiform bones. A latissimus dorsi free flap was used to
      reconstruct the defect. A functional pseudoarthrosis developed between the
      remaining bones of the foot, and the patient experienced satisfactory foot
      function after rehabilitation. For this reason, no additional reconstructive
      procedure was undertaken. This case suggests that it might be adequate to use the
      latissimus dorsi muscle flap more liberally than previously reported in the
      reconstruction of extensive defects of the dorsum of the foot, including cases
      with significant bone loss. This option could avoid the morbidity and
      inconvenience of a second surgery and the need to harvest a bone flap or graft.

PMID- 21945401
TI  - Volumetric MRI and 1H MRS study of hippocampus in unilateral MCAO patients:
      relationship between hippocampal secondary damage and cognitive disorder
      following stroke.
AB  - OBJECTIVE: To determine whether hippocampi alter in patients at the recovery
      stage of middle cerebral artery occlusion (MCAO) and whether the changes of
      hippocampi involve in the cognitive impairment in such patients. MATERIALS AND
      METHODS: [corrected] Forty-four patients with unilateral infarction solely in
      MCAO territory and 44 age-, sex- and education background-matched healthy
      volunteers were enrolled in this study. All subjects underwent 3-dimensional fast
      spoiled gradient-echo (3D FSPGR) and sing-voxel proton magnetic resonance
      spectroscopy ((1)H MRS) protocols at a 1.5 T MR scanner. The ratios of n
      acetylaspartate/creatine (NAA/Cr) and myo-inositol/creatine (mI/Cr) were obtained
      by using software integrated in the MR scanner. The hippocampal volumes were
      estimated by manually measurement. RESULTS: The volume and NAA/Cr ratio were
      found significantly decreased and mI/Cr ratio significantly increased in the
      hippocampus ipsilateral to occluded middle cerebral artery (MCA) as compared with
      values in the contralateral hippocampus or healthy control. A reduced NAA/Cr
      ratio was also observed in contralateral hippocampus compared to controls. The
      shrinkage ratio of hippocampus ipsilateral to MCAO was found related to the Mini
      Mental State Examination (MMSE) score. CONCLUSION: Our study identified that the
      hippocampal secondary damage occurred in patients after MCAO, and it could be
      evaluated noninvasively by volumetric magnetic resonance imaging (MRI) and (1)H
      MRS. Moreover, the hippocampal secondary damage in MCAO patients indeed
      contributed to their cognitive impairment.

PMID- 21945402
TI  - Efficacy of diphenhydramine in the prevention of vertigo and nausea at 7 T MRI.
AB  - PURPOSE: In this study the potential of diphenhydramine in reducing respectively
      preventing vertigo and nausea induced by the ultra-high static magnetic field at
      7 T was evaluated. MATERIALS AND METHODS: In a prospective, double blinded,
      placebo controlled, cross-over randomized study the sensations of 34 volunteers
      before, during and after exposure to the static magnetic field with and without
      drug respectively placebo administration were quantified. Fast table motion was
      applied to increase the incidence of otherwise sparse reports of field related
      sensations. RESULTS: The strength of vertigo can be reduced by the application of
      diphenhydramine. CONCLUSION: Diphenhydramine, even at a low dose, reduces the
      strength of vertigo at ultra-high static magnetic fields, may be used
      preventively, and could pave the way to even higher field strength.

PMID- 21945403
TI  - Patterns of pulmonary tuberculosis on FDG-PET/CT.
AB  - OBJECTIVE: This study aims to describe patterns of pulmonary tuberculosis (TB) on
      FDG-PET/CT. METHODS: All patients with a diagnosis of TB and who underwent FDG
      PET/CT between January 2009 and June 2010 were included. Clinical, biological and
      imaging data were reviewed. TB was proven either on bacteriological or
      histopathological studies (n=13) or on a clinical and imaging basis (n=3).
      RESULTS: Sixteen patients (11 men; median age 56, range 22-84 years) were
      included. Two distinct patterns were identified. In the lung pattern (9/16),
      patients had predominantly pulmonary symptoms (6/9 patients, 67%) with a
      parenchymal involvement: uptakes on lung consolidation +/- cavitation surrounded
      by micronodules. Mediastino-hilar lymph nodes were slightly enlarged (15 mm, 10
      27) with moderate uptake (3.9, 2.5-13.4). In the lymphatic pattern (7/16),
      patients had predominantly systemic symptoms (5/7 cases, 71%) and all had extra
      thoracic involvement. Mediastino-hilar lymph nodes were more enlarged (30 mm, 18
      35, p=0.03) and with higher uptake (6.8, 5.7-16.8, p=0.034) than in the lung
      pattern. CONCLUSION: We identified two distinct patterns of pulmonary TB on FDG
      PET/CT. The lung pattern related to a restricted and slight hypermetabolic
      infection and the lymphatic pattern related to a systemic and intense infection.
      Combined interpretation of PET and CT findings improves the specificity of
      images, especially for the lung pattern.

PMID- 21945404
TI  - Bi-stability, hysteresis, and memory of voltage-gated lysenin channels.
AB  - Lysenin, a 297 amino acid pore-forming protein extracted from the coelomic fluid
      of the earthworm E. foetida, inserts constitutively open large conductance
      channels in natural and artificial lipid membranes containing sphingomyelin. The
      inserted channels show voltage regulation and slowly close at positive applied
      voltages. We report on the consequences of slow voltage-induced gating of lysenin
      channels inserted into a planar Bilayer Lipid Membrane (BLM), and demonstrate
      that these pore-forming proteins constitute memory elements that manifest gating
      bi-stability in response to variable external voltages. The hysteresis in
      macroscopic currents dynamically changes when the time scale of the voltage
      variation is smaller or comparable to the characteristic conformational
      equilibration time, and unexpectedly persists for extremely slow-changing
      external voltage stimuli. The assay performed on a single lysenin channel reveals
      that hysteresis is a fundamental feature of the individual channel unit and an
      intrinsic component of the gating mechanism. The investigation conducted at
      different temperatures reveals a thermally stable reopening process, suggesting
      that major changes in the energy landscape and kinetics diagram accompany the
      conformational transitions of the channels. Our work offers new insights on the
      dynamics of pore-forming proteins and provides an understanding of how channel
      proteins may form an immediate record of the molecular history which then
      determines their future response to various stimuli. Such new functionalities may
      uncover a link between molecular events and macroscopic processing and
      transmission of information in cells, and may lead to applications such as high
      density biologically-compatible memories and learning networks.

PMID- 21945405
TI  - Subdural spinal haematoma after spinal anaesthesia in a patient taking aspirin.
AB  - Haematoma in the spinal canal may be catastrophic if the condition is not
      detected and treated early. In the enclosed spinal canal, even a small space
      occupying lesion may be rapidly symptomatic. Clinical presentation ranges from
      benign back pain to severe neurological deficits, the nature of which depends on
      the level of compression (cauda equina or spinal cord). Despite surgical
      decompression and extended rehabilitation, many patients suffer permanent
      disability. Aspirin use prior to neuraxial block is not generally contraindicated
      in the literature but we would recommend withholding the anticoagulant, if safe,
      or considering an alternative form of anaesthesia.

PMID- 21945406
TI  - Evaluation of the QIAsymphonyTM SP and ArtusTM RealTime extraction-quantification
      systems for measuring HIV-1 virus load.
AB  - BACKGROUND: Automated HIV-1 RNA extraction and its quantification by real-time
      PCR assays provide improved sample processing and better analytical performances.
      The new Artus HIV-1 RealTime assay can be performed after automated extraction
      with the Qiagen Qiasymphony robot. OBJECTIVES AND STUDY DESIGN: To evaluate the
      sensitivity, reproducibility, linearity, ability to detect HIV-1 subtypes of the
      Qiagen Qiasymphony and RealTime Artus HIV-1 assay system and to compare with the
      Roche Cobas Ampliprep Cobas TaqMan assay, vs 2.0 (CAP/CTM; Roche Molecular
      Systems). RESULTS: The detection limit calculated by probit analysis was 65 c/ml
      using dilutions of a NIBSC. Assays of serially diluted clinical samples gave very
      good inter-assay and intra-assay reproducibilities (<10% CV) and linearity (2.2
      6.5 log copies/ml). The results ArtusTM HIV-1 and CAP/CTM assays provided very
      similar results: average difference=0.11 log copies/ml. The ArtusTM titers for 18
      (22%) of the 114 HIV-1 group M samples tested differed by over 0.5 log copies/ml
      from the CAP/CTM titers. The ArtusTM values were lower than the CAP/CTM values in
      83% of cases. Discrepant results were not associated with particular subtypes.
      CONCLUSION: The ArtusTM HIV-1 assay reliably quantified the HIV RNA in clinical
      specimens. Analytical performances were good and it integrated well with the
      Qiasymphony automated RNA extraction procedure. It appears to be appropriate for
      monitoring therapy and the routine management of HIV-1 infections.

PMID- 21945407
TI  - The peroxynitrite donor 3-morpholinosydnonimine activates Nrf2 and the UPR
      leading to a cytoprotective response in endothelial cells.
AB  - Endothelial dysfunction is associated with the formation of peroxynitrite,
      described to be toxic. Recent data also suggests that peroxynitrite is able to
      activate the protective Nrf2 pathway and/or the unfolded protein response (UPR).
      The aim of our work was to study the response of human endothelial cells to 3
      morpholinosydnonimine (SIN-1), a peroxynitrite donor, and to highlight the
      possible protective roles of Nrf2 or the UPR pathway in this response. Immortal
      and primary human umbilical vein endothelial cells were exposed to SIN-1. SIN-1
      incubation led to Nrf2 activation and to the overexpression of Nrf2-regulated
      genes, heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1. We also
      demonstrated that this defensive response protected cells against cell death
      induced by serum starvation, by reducing apoptosis (monitored by caspase-3
      activity and DNA fragmentation) and favoring autophagosome formation, as
      evidenced by LC3-II accumulation. Interestingly, we observed an activation of the
      UPR, with a rapid and significant overexpression of CHOP in serum starved cells
      stimulated with SIN-1. While siRNA mediated knockdown of CHOP had no effect on
      DNA fragmentation, the invalidation of Nrf2 or HO-1 by siRNA strongly increased
      DNA fragmentation, but also reinforced the SIN-1-induced LC3-II accumulation.
      This study shows that peroxynitrite, at least at sublethal concentrations and
      within a narrow concentration range, could exert protective effects on
      endothelial cells by modulating the balance between autophagy and apoptosis,
      through Nrf2-dependent pathways.

PMID- 21945408
TI  - Healing the diabetic heart: does myocardial preconditioning work?
AB  - Diabetes mellitus-associated ischemic heart disease is a major public burden in
      industrialized countries. Reperfusion to a previously ischemic myocardium is
      obligatory to reinstate its function prior to irreversible damage. However,
      reperfusion is considered 'a double-edged sword' as reperfusion per se could
      augment myocardial ischemic damage, known as myocardial ischemia-reperfusion
      (I/R) injury. The brief and repeated cycles of I/R given before a sustained
      ischemia and reperfusion are represented as ischemic preconditioning, which
      protects the heart from lethal I/R injury. Few studies have demonstrated
      preconditioning-mediated cardioprotection in the diabetic heart. In contrast,
      considerable number of studies suggests that myocardial defensive effects of
      preconditioning are abolished in the presence of chronic diabetes mellitus that
      raised questions over preconditioning effects in the diabetic heart. It is
      evidenced that chronic diabetes mellitus-associated deficit in survival pathways,
      impaired function of mito-K(ATP) channels, MPTP opening and high oxidative stress
      play key roles in paradoxically suppressed cardioprotective effects of
      preconditioning in the diabetic heart. These controversial results open up a new
      area of research to identify potential mechanisms influencing disparities on
      preconditioning effects in diabetic hearts. In this review, we discussed first
      the discrepancies on the modulatory role of diabetes mellitus in I/R-induced
      myocardial injury. Following this, we addressed whether preconditioning could
      protect the diabetic heart against I/R-induced myocardial injury. Moreover,
      potential mechanisms pertaining to the attenuated cardioprotective effects of
      preconditioning in the diabetic heart have been delineated. These are important
      to be understood for better exploitation of preconditioning strategies in
      limiting I/R-induced myocardial injury in the diabetic heart.

PMID- 21945409
TI  - Distinct bone morphogenetic proteins activate indistinguishable transcriptional
      responses in nephron epithelia including Notch target genes.
AB  - Endogenous Bone Morphogenetic Protein (BMP) signaling plays a significant role in
      the kidney's recovery from acute injury and exogenous administration of BMP7 has
      therapeutic potential in numerous rodent models of renal injury and disease.
      However, in the healthy kidney endogenous BMP7 ligand is vigorously counteracted
      by extracellular antagonists such as USAG1 and CHRDL1. Little is known about the
      degree of BMP signaling and the ligands driving it in the healthy adult kidney.
      In this study we characterize basal BMP signaling in the healthy tubular nephron,
      and show that BMP2 is expressed in proximal nephron epithelial cells. Comparative
      gene profiling of proximal tubule cell responses to BMP2 and BMP7 does not reveal
      any qualitative difference, suggesting that identical BMP gene targets may be
      activated in healthy and injured organs. Interestingly, our gene profiling
      analysis shows that BMP signaling activates a number of Notch regulated
      transcription factors, including HEY1. As in other biological systems, HEY1
      functions as a negative feedback regulator of BMP2 expression in the proximal
      tubule. In summary, this work reveals endogenous BMP signaling patterns in the
      healthy human and mouse kidneys, and identifies novel gene targets, some of which
      are involved in the complex regulation of BMP signaling in the adult kidney.

PMID- 21945410
TI  - Photocatalytic oxidation of DBP precursors using UV with suspended and fixed
      TiO2.
AB  - French River water (Nova Scotia, Canada) was separated into six different natural
      organic matter (NOM) fractions, including hydrophobic acids, bases and neutrals
      and hydrophilic acids, bases and neutrals. The raw water, as well as each of the
      NOM fractions were analysed for disinfection by-product (DBP) formation potential
      before and after advanced oxidation with UV/TiO(2) to determine the efficacy of
      this treatment for the removal of DBP precursors. The UV/TiO(2) treatment was
      carried out with a nanostructured thin film (NSTF), coated with TiO(2) which is
      compared with the use of a TiO(2) suspension. For the raw river water, removals
      of total trihalomethane formation potential (TTHMFP) and total haloacetic acid
      formation potential (THAA(9)FP) were found to be approximately 20% and 90%,
      respectively, with 50 mJ/cm(2) UV exposure and 1mg/L TiO(2). For the fractionated
      samples, approximately 75% of both trihalomethane (THM) and haloacetic acid (HAA)
      precursors were found to be associated with the hydrophobic acid fraction. For
      this individual fraction the same UV/TiO(2) treatments exhibited approximately 20
      25% removal of both TTHMFP and THAA(9)FP, suggesting that the fractionation
      process may have affected the treatability of HAA precursors or may have altered
      the results of the oxidation processes.

PMID- 21945411
TI  - Impact of fibroblast growth factor-binding protein-1 expression on angiogenesis
      and wound healing.
AB  - Fibroblast growth factors (FGFs) participate in embryonic development, in
      maintenance of tissue homeostasis in the adult, and in various diseases. FGF
      binding proteins (FGFBP) are secreted proteins that chaperone FGFs stored in the
      extracellular matrix to their receptor, and can thus modulate FGF signaling.
      FGFBP1 (alias BP1, FGF-BP1, or HBp17) expression is required for embryonic
      survival, can modulate FGF-dependent vascular permeability in embryos, and is an
      angiogenic switch in human cancers. To determine the function of BP1 in vivo, we
      generated tetracycline-regulated conditional BP1 transgenic mice. BP1-expressing
      adult mice are viable, fertile, and phenotypically indistinguishable from their
      littermates. Induction of BP1 expression increased mouse primary fibroblast
      motility in vitro, increased angiogenic sprouting into subcutaneous matrigel
      plugs in animals and accelerated the healing of excisional skin wounds. FGF
      receptor kinase inhibitors blocked these effects. Healing skin wounds showed
      increased macrophage invasion as well as cell proliferation after BP1 expression.
      Also, BP1 expression increased angiogenesis during the healing of skin wounds as
      well as after ischemic injury to hindlimb skeletal muscles. We conclude that BP1
      can enhance FGF effects that are required for the healing and repair of injured
      tissues in adult animals.

PMID- 21945412
TI  - Off-label gabapentin masking ictal triphasic waves: case analysis of
      neuropsychiatric and electrographic correlates.
AB  - Antiepileptic drugs (AEDs) are frequently used off-label for the treatment of
      psychiatric, pain, and other neurological disorders. Off-label AED use may
      confound the diagnosis for acute neuropsychiatric changes associated with
      delirium by fortuitously treating, or partially treating, underlying seizure
      disorders while masking ictal electrographic patterns on EEGs. Standard video/EEG
      monitoring includes weaning from AEDs to maximize ictal activity and better
      determine seizure focus. We report a case of off-label gabapentin use masking
      ictal electrographic activity, the neuropsychiatric and electrographic
      consequences of discontinuing gabapentin, and the therapeutic response when
      gabapentin was re-initiated and titrated to a total daily dose greater than that
      at time of admission. Weaning from AEDs with concurrent video/EEG monitoring is
      an important diagnostic tool in these complex cases.

PMID- 21945413
TI  - Stress during development alters anxiety-like behavior and hippocampal
      neurotransmission in male and female rats.
AB  - Epidemiological data indicate that early stress increases vulnerability to
      psychiatric disorders, including anxiety and depression. In the present study we
      sought to investigate the long-term behavioral and neurochemical consequences of
      increased and sustained corticosterone levels induced by a 24 h bout of maternal
      deprivation (DEP) imposed on postnatal day 11 (DEP11). As adults, animals were
      exposed to the elevated plus maze for assessment of anxiety-like behavior and
      corticosterone response to this challenge, or decapitated for determination of
      monoamines and amino acid neurotransmitters content in the hippocampus by HPLC
      method. The results showed that DEP11 male and female rats displayed increased
      time in the central hub of the maze and more risk assessment behavior, reflecting
      increased anxiety-like behavior; in addition, these animals continuously secreted
      corticosterone in response to the behavioral test until the latest time-point,
      e.g., 60 min post-stress. In males, maternal deprivation increased aspartate and
      glutamate levels and reduced taurine levels compared to non-deprived (NDEP) rats.
      DEP11 females displayed reduced noradrenaline, aspartate and GABA levels compared
      to NDEP counterparts. These results indicate that maternal deprivation at 11 days
      of age produced changes in hippocampal neurotransmission that may mediate the
      increased anxiety-like behavior observed in male and female deprived rats. This
      article is part of a Special Issue entitled 'Anxiety and Depression'.

PMID- 21945414
TI  - Genotoxic effects of silver nanoparticles stimulated by oxidative stress in human
      normal bronchial epithelial (BEAS-2B) cells.
AB  - Many classes of silver nanoparticles (Ag-NPs) have been synthesized and widely
      applied, but the genotoxicity of Ag-NPs and the factors leading to genotoxicity
      remain unknown. Therefore, the purpose of this study is to elucidate the
      genotoxic effects of Ag-NPs in lung and the role of oxidative stress on the
      genotoxic effects of Ag-NPs. For this, Ag-NPs were completely dispersed in medium
      by sonication and filtration. The Ag-NPs dispersed in medium were 43-260nm in
      size. We observed distinct uptake of Ag-NPs into BEAS-2B cells. The Ag-NPs
      aggregates were wrapped with an endocytic vesicle within the cytoplasm and
      nucleus of BEAS-2B cells. In the comet assay and micronucleus (MN) assay for BEAS
      2B cells, Ag-NPs stimulated DNA breakage and MN formation in a dose-dependent
      manner. The genotoxic effect of Ag-NPs was partially blocked by scavengers. In
      particular, of the scavengers tested, superoxide dismutase most significantly
      blocked the genotoxic effects in both the cytokinesis-block MN assay and the
      comet assay. In the modified comet assay, Ag-NPs induced a significant increase
      in oxidative DNA damage. Furthermore, in the oxidative stress assay, Ag-NPs
      significantly increased the reactive oxygen radicals. These results suggest that
      Ag-NPs have genotoxic effects in BEAS-2B cells and that oxidative stress
      stimulated by Ag-NPs may be an important factor in their genotoxic effects.

PMID- 21945415
TI  - Identification and characterization of a chitinase of Stenotrophomonas
      maltophilia, a bacterium that is antagonistic towards fungal phytopathogens.
AB  - A rhizosphere strain of Stenotrophomonas maltophilia strain MUJ that is strongly
      antagonistic towards fungal phytopathogens secretes to the culture medium a
      single form of active chitinolytic enzyme belonging to family 18 of glycosyl
      hydrolases. The chitinase was purified by a two-stage procedure embracing
      fractionation with ammonium sulfate and affinity chromatography. The molecular
      mass of the purified enzyme determined by SDS-PAGE was approximately 52 kDa. The
      enzyme demonstrated highest activity at 45 degrees C and pH 6.8. The enzymatic
      protein showed considerable thermal stability during 2 h incubation at 45 degrees
      C. The activity of the enzyme was strongly inhibited in the presence of Hg2+ and
      Cu2+. By applying mass spectrometry analysis, the peptides derived from the
      purified chitinase were assigned to amino acid sequences of the type ChiA
      chitinases synthesized by Stenotrophomonas bacteria. The purified enzyme
      inhibited the growth of fungal phytopathogens belonging to the genera Fusarium,
      Rhizoctonia and Alternaria.

PMID- 21945416
TI  - Major furocoumarins in grapefruit juice I: levels and urinary metabolite(s).
AB  - Furocoumarins are phototoxic and photogenotoxic natural plant constituents
      occurring in cosmetics, food and drugs. Grapefruit juice is considered as a major
      dietary source of furocoumarins although few is known about the variability of
      furocoumarins in grapefruit juice. We analyzed the major furocoumarins in eight
      commercial grapefruit juices and in freshly prepared juices made from pink
      grapefruit obtained from German retailers. Bergaptol was the major furocoumarin
      in commercial juices, followed by bergamottin and 6',7'-dihydroxy-bergamottin
      (DHB), whereas an inverse picture (DHB>bergamottin>bergaptol) was obtained in
      freshly prepared juices. Results from different batches of a single brand of
      commercial juice, purchased over a period of 7 months, revealed a variability of
      about 50% for the individual furocoumarins and the sum. In a study with healthy
      volunteers, consumption of 900 ml commercial grapefruit juice (containing 12.5mg
      bergaptol, 6.9 mg bergamottin, and 0.6 mg DHB) resulted in an average urinary
      excretion of 0.36 mg free plus 13.23 mg conjugated bergaptol within 6h. Other
      furocoumarins were not found in urine. Thus, other grapefruit furocoumarins were
      obviously converted in the human body, at least in part, into bergaptol excreted
      in urine, since the excreted amount of bergaptol exceeded the consumed one.

PMID- 21945417
TI  - Urinary tract infection after colon and rectal resections: more common than
      predicted by risk-adjustment models.
AB  - BACKGROUND: Urinary tract infections (UTIs) are the most common hospital-acquired
      infections in the United States. We hypothesized that the risk of UTI after
      colorectal surgery exceeds the risk after other gastrointestinal operations.
      STUDY DESIGN: We used National Surgical Quality Improvement Program (NSQIP) data
      from 2005 to 2008 to compute rates of UTI after colorectal resections and other
      gastrointestinal and general surgery. We used a validated multivariate UTI
      prediction model to compare risk-adjusted rates of UTI by type of procedure. Then
      we identified predictors of UTI after colorectal resection using stepwise
      logistic regression models. RESULTS: Crude UTI rates were significantly greater
      after colorectal resection (4.1%) than after other gastrointestinal (1.8%) or
      nongastrointestinal procedures (1.2%; all p < 0.001). Even using standard risk
      adjustment from the NSQIP, rates of UTI were significantly higher after segmental
      colectomy (2.8%; 95% CI 2.5% to 3.2%), total colectomy (3.5%; 95% CI 2.9% to
      4.3%), proctectomy (3.5%, 95% CI 3.1% to 4.2%), proctocolectomy (4.6%, 95% CI
      3.8% to 5.7%), and abdominoperineal resection (5.6%, 95% CI 4.6% to 6.8%) than
      after noncolorectal gastrointestinal surgery (2.6%, 95% CI 2.2% to 2.9%). Factors
      associated with UTI after colorectal resections include age, sex, functional
      status, American Society of Anesthesiologists class, and resection type.
      CONCLUSIONS: Colorectal resections incur substantial risk of postoperative UTI,
      exceeding rates predicted by the NSQIP model. Because of their patients'
      unanticipated high incidence of UTI, surgeons with a specialty interest in
      colorectal surgery risk being flagged as "high outliers," particularly if they
      perform many rectal resections. A simple set of risk factors discriminates 10
      fold differences in the rate of UTI after colorectal resection.

PMID- 21945419
TI  - Gallbladder carcinoma with anomalous pancreaticobiliary junction.

PMID- 21945418
TI  - Overexpression of megsin induces mesangial cell proliferation and excretion of
      type IV collagen in vitro.
AB  - Over-expression of megsin is associated with mesangial cell (MC) proliferation
      and extracellular matrix (ECM) accumulation. The underlying pathogenesis is
      unknown. This study demonstrate that over-expression of megsin induced
      incorporation of [(3)H]thymidine in MCs and PDGF-BB, TGF-beta1 upregulation.
      Concentrations of PDGF-BB, TGF-beta1 and type IV collagen in the culture medium
      of MCs transfected with megsin were higher than controls. Anti-PDGF-BB suppressed
      incorporation of [(3)H]thymidine in MCs transfected with megsin and mRNA
      expression of TGF-beta1 in stable transformant MCs, suggesting that over
      expression of megsin induces cell proliferation and ECM accumulation in MCs,
      upregulation of PDGF-BB and TGF-beta1 is probably the main route involved in
      pathogenesis.

PMID- 21945420
TI  - Archaeal CRISPR-based immune systems: exchangeable functional modules.
AB  - CRISPR (clustered regularly interspaced short palindromic repeats)-based immune
      systems are essentially modular with three primary functions: the excision and
      integration of new spacers, the processing of CRISPR transcripts to yield mature
      CRISPR RNAs (crRNAs), and the targeting and cleavage of foreign nucleic acid. The
      primary target appears to be the DNA of foreign genetic elements, but the
      CRISPR/Cmr system that is widespread amongst archaea also specifically targets
      and cleaves RNA in vitro. The archaeal CRISPR systems tend to be both diverse and
      complex. Here we examine evidence for exchange of functional modules between
      archaeal systems that is likely to contribute to their diversity, particularly of
      their nucleic acid targeting and cleavage functions. The molecular constraints
      that limit such exchange are considered. We also summarize mechanisms underlying
      the dynamic nature of CRISPR loci and the evidence for intergenomic exchange of
      CRISPR systems.

PMID- 21945421
TI  - Effects of alcohol consumption on biomarkers of oxidative damage to DNA and
      lipids in ethanol-fed pigs.
AB  - Chronic alcohol consumption is known to result in tissue injury, particularly in
      the liver, and is considered a major risk factor for cancers of the upper
      respiratory tract. Here we assessed the oxidative effects of subchronic ethanol
      consumption on DNA and lipids by measuring biomarkers 8-oxo-7,8-dihydro-2'
      deoxyguanosine (8-oxodG) and malondialdehyde (MDA), respectively. Physiological
      responses of pigs (n = 4) administered ethanol in drinking water for 39 days were
      compared with those of water-fed pigs (n = 4). Alcoholisation resulted in serum
      ethanol concentration of 1.90 g L(-1) and in a moderate but significant increase
      in alanine aminotransferase activity, an index of liver injury. However, between
      the alcoholised and control groups there were no significant differences in the
      levels of 8-oxodG (8-oxodG per 10(6) 2'deoxyguanosine) from leucocytes (2.52 +/-
      0.42 Vs 2.39 +/- 0.34) or from target organs, liver, cardia and oesophagus. Serum
      MDA levels were also similar in ethanol-fed pigs (0.33 +/- 0.04 MUM) and controls
      (0.28 +/- 0.03 MUM). Interestingly, levels of 8-oxodG in cardia were positively
      correlated with those in oesophagus (Spearman correlation coefficient R = 1, P <
      0.0001). Our results suggest that alcohol consumption may not cause oxidative
      damage to DNA and lipids as measured by 8-oxodG and MDA, respectively. The
      duration of alcoholisation and the potential alcohol-induced nutritional
      deficiency may be critical determinants of ethanol toxicity. Relevant biomarkers,
      such as factors involved in sensitization to ethanol-induced oxidative stress are
      required to better elucidate the relationship between alcohol consumption,
      oxidative stress and carcinogenesis.

PMID- 21945422
TI  - Functional characterization of codCath, the mature cathelicidin antimicrobial
      peptide from Atlantic cod (Gadus morhua).
AB  - Cathelicidins are among the best characterized antimicrobial peptides and have
      been shown to have an important role in mammalian innate immunity. We recently
      isolated a novel mature cathelicidin peptide (codCath) from Atlantic cod and in
      the present study we functionally characterized codCath. The peptide demonstrated
      salt sensitivity with abrogation of activity at physiological salt
      concentrations. In low ionic strength medium we found activity against marine and
      non-marine Gram-negative bacteria with an average MIC of 10 MUM, weak activity
      against a Gram-positive bacterium (MIC 80 MUM), and pronounced antifungal
      activity (MIC 2.5 MUM). The results suggest the kinetics and mode of action of
      codCath to be fast killing accompanied by pronounced cell lysis. Extracellular
      products (ECPs) of three marine bacteria caused breakdown of the peptide into
      smaller fragments and the cleaved peptide lost its antibacterial activity.
      Proteolysis of the peptide on the other hand was abolished by prior heat
      treatment of the ECPs, suggesting a protease involvement. We observed no
      cytotoxicity of the peptide in fish cells up to a concentration of 40 MUM and the
      selectivity of activity was confirmed with bacterial and mammalian membrane
      mimetics. We conclude that the potent broad-spectrum activity of codCath hints at
      a role of the peptide in cod immune defense.

PMID- 21945423
TI  - Vascular mechanisms involved in angiotensin II-induced venoconstriction in
      hypertensive rats.
AB  - To investigate the venoconstrictor effect of angiotensin II (Ang II) in
      spontaneously hypertensive rats (SHR), we used preparations of mesenteric venular
      beds and the circular muscle of the portal veins. Vessels were tested with Ang II
      in the presence or absence of losartan, PD 123319, HOE 140, L-NAME, indomethacin,
      or celecoxib. In the mesenteric venular bed of SHR, the effect of Ang II (0.1
      nmol) was nearly abolished by losartan and enhanced by HOE 140, indomethacin, and
      celecoxib, while PD123319 and L-NAME had no effect. In portal vein preparations,
      cumulative-concentration response curves (CCRC) to Ang II (0.1-100 nmol/L)
      exhibited a lower maximal response (E(max)) in SHR compared to Wistar rats. AT(1)
      receptor expression was similar in the two strains, while AT(2) receptor levels
      were lower in SHR portal veins when compared to Wistar. In SHR portal veins,
      losartan shifted the CCRC to Ang II to the right, while indomethacin and HOE 140
      increased the E(max) to Ang II. PD 123319, celecoxib, and L-NAME had no effect.
      Taken together, our results suggest that Ang II-induced venoconstriction in SHR
      is mediated by activation of AT(1) receptors and this effect may be
      counterbalanced by kinin B(2) receptor and COX metabolites. Furthermore, our data
      indicate that there are different cellular and molecular mechanisms involved in
      the regulation of venous tonus of normotensive and hypertensive rats. These
      differences probably reflect distinct factors that influence arterial and venous
      bed in hypertension.

PMID- 21945424
TI  - The quality of the maternal health system in Eritrea.
AB  - OBJECTIVE: To examine the quality of the maternal health system in Eritrea to
      understand system deficiencies and its relevance to maternal mortality within the
      context of Millennium Development Goal (MDG) 5. METHODS: A sample of 118 health
      facilities was surveyed. Data were collected on 5 dimensions of health system
      quality: availability; accessibility; management; infrastructure; and process
      indicators. Data on the causes of hospital admissions for obstetric patients and
      maternal deaths were extracted from medical records. RESULTS: Eritrea has only 11
      comprehensive emergency obstetric care (CEmOC) facilities, all of which are
      grossly understaffed. There is considerable pressure on the infrastructure and
      health providers at hospitals. Compliance with clinical care standards and
      availability of supplies were optimal. As a result, the case fatality rate of
      0.65% was low. In total, 45.6% of obstetric admissions and 19.5% of maternal
      deaths were attributed to abortion complications. CONCLUSION: In Eritrea,
      critical gaps in the health system-especially those related to human resources
      will impede progress toward MDG 5, and it will not be possible to reduce maternal
      mortality without addressing the high burden of abortion.

PMID- 21945425
TI  - Oxygen binding properties of backswimmer (Notonectidae, Anisops) haemoglobin,
      determined in vivo.
AB  - Aquatic backswimmers (Anisops spp.) collect oxygen from the atmosphere in order
      to breathe underwater, carrying it within a bubble of air on the ventral surface
      of their body and bound within haemoglobin-filled cells inside their abdomen.
      These oxygen stores are interconnected via the abdominal spiracles and the
      tracheal system. Fibre optic oxygen probes were used to measure PO(2) changes
      within the air bubbles of submerged backswimmers (Anisops deanei) and these
      measurements were transformed into in vivo haemoglobin-oxygen equilibrium curves
      (OECs) using a biotonometric approach. The haemoglobin displayed a triphasic,
      highly sigmoid OEC with a P(50) of 3.90 kPa. Comparisons made with a previous in
      vitro analysis of Anisops haemoglobin demonstrate that while the apparent
      cooperativity and oxygen affinity are considerably higher in vivo, both
      measurements share unusual Hb-O(2) binding characteristics. The affinity and
      cooperativity of the backswimmers' haemoglobin appears adaptive as it lengthens
      dives and promotes neutral buoyancy. While there are limitations associated with
      biotonometry, the in vivo OEC accurately represents the loading and unloading of
      biologically available oxygen within the backswimmers' haemoglobin cells.
      Potential errors associated with determining the OEC are small, as evaluated with
      sensitivity analyses in numerical models.

PMID- 21945426
TI  - A fuzzy-genetic model for estimating forces from electromyographical activity of
      antagonistic muscles due to planar lower arm movements: the effect of nonlinear
      muscle properties.
AB  - The aim of this paper is to create a model for mapping the surface electromyogram
      (EMG) signals to the force that generated by human arm muscles. Because the
      parameters of each person's muscle are individual, the model of the muscle must
      have two characteristics: (1) The model must be adjustable for each subject. (2)
      The relationship between the input and output of model must be affected by the
      force-length and the force-velocity behaviors are proven through Hill's
      experiments. Hill's model is a kinematic mechanistic model with three elements,
      i.e. one contractile component and two nonlinear spring elements. In this
      research, fuzzy systems are applied to improve the muscle model. The advantages
      of using fuzzy system are as follows: they are robust to noise, they prove an
      adjustable nonlinear mapping, and are able to model the uncertainties of the
      muscle. Three fuzzy coefficients have been added to the relationships of force
      length (active and passive) and force-velocity existing in Hill's model. Then, a
      genetic algorithm (GA) has been used as a biological search method that can
      adjust the parameters of the model in order to achieve the optimal possible fit.
      Finally, the accuracy of the fuzzy genetic implementation Hill-based muscle model
      (FGIHM) is invested as following: the FGIHM results have 12.4% RMS error (in
      worse case) in comparison to the experimental data recorded from three healthy
      male subjects. Moreover, the FGIHM active force-length relationship which is the
      key characteristics of muscles has been compared to virtual muscle (VM) and Zajac
      muscle model. The sensitivity of the FGIHM has been evaluated by adding a white
      noise with zero mean to the input and FGIHM has proved to have lower sensitivity
      to input noise than the traditional Hill's muscle model.

PMID- 21945427
TI  - Optimizing the baculovirus expression vector system.
AB  - Baculoviruses have a unique bi-phasic life cycle and powerful promoters, which
      greatly facilitates their use for recombinant protein expression in insect cells.
      We have developed an expression system that utilizes homologous recombination in
      insect cells between a transfer plasmid containing a gene to be expressed and a
      replication-deficient virus (bacmid). Only recombinant virus can replicate
      facilitating the rapid production of multiple recombinant viruses using robotic
      liquid handlers. The bacmid has also been genetically optimized for improved
      protein expression and stability. We describe the application of this system for
      high level production of recombinant proteins.

PMID- 21945429
TI  - Prevalence and proposal for cost-effective management of the ciguatera risk in
      the Noumea fish market, New Caledonia (South Pacific).
AB  - Ciguatera fish poisoning (CFP) is a common intoxication associated with the
      consumption of reef fish, which constitutes a critical issue for public health in
      many countries. The complexity of its epidemiology is responsible for the poor
      management of the risk in tropical fish markets. We used the example of the
      Noumea fish market in New Caledonia to develop a cost-effective methodology of
      assessing the CFP risk. We first used published reports and the knowledge of
      local experts to define a list of potentially poisonous local species, ranked by
      their ciguatoxic potential. Based on two 1-month surveys in the market, conducted
      in winters 2008 and 2009, we then calculated the consolidated ratio of biomass of
      potentially poisonous species vs. total biomass of fish sold on the market. The
      prevalence of high CFP-risk species in the market was 16.1% and 18.9% in 2008 and
      2009, respectively. The most common high CFP risk species were groupers
      (serranids), king mackerels (scombrids), snappers (lutjanids), barracudas
      (sphyaraenids), emperors (lethrinids) and wrasses (labrids). The size (age) of
      the fish also plays a critical role in the potential ciguatoxic risk. According
      to proposals of average size thresholds provided by experts for high-risk
      species, we were also able to assess the additional risk induced by the sale of
      some large fish on the market. The data collected both from experts and from the
      market allowed us to develop a cost-effective proposal for improving the
      management of the CFP risk in this market. However, the successful implementation
      of any regulation aiming to ban some specific species and sizes from the market,
      with an acceptable economical impact, will require the improvement of the
      expertise in fish identification by public health officers and, ideally, the
      commitment of retailers.

PMID- 21945428
TI  - Oral colonization by Streptococcus mutans and caries development is reduced upon
      deletion of carbonic anhydrase VI expression in saliva.
AB  - Carbonic anhydrase VI (CA VI), encoded by type A transcripts of the gene Car6, is
      a secretory product of salivary glands and is found in the enamel pellicle.
      Because higher caries prevalence is associated with lower salivary concentrations
      of CA VI in humans, we tested whether CA VI protects enamel surfaces from caries
      induced by Streptococcus mutans, using Car6(-/-) mice, in which salivary CA VI
      expression is absent. We detected aberrant Car6 type A transcripts in Car6(-/-)
      mice, likely targets for nonsense-mediated mRNA decay. Expression of the
      intracellular stress-induced isoform of CA VI encoded by type B transcripts was
      restricted to parotid and submandibular glands of wild type mice. The salivary
      function of Car6(-/-) mice was normal as assessed by the histology and
      protein/glycoprotein profiles of glands, salivary flow rates and
      protein/glycoprotein compositions of saliva. Surprisingly, total smooth surface
      caries and sulcal caries in Car6(-/-) mice were more than 6-fold and 2-fold lower
      than in wild type mice after infection with S. mutans strain UA159. Recoveries of
      S. mutans and total microbiota from molars were also lower in Car6(-/-) mice. To
      explore possible mechanisms for increased caries susceptibility, we found no
      differences in S. mutans adherence to salivary pellicles, in vitro.
      Interestingly, higher levels of Lactobacillus murinus and an unidentified
      Streptococcus species were cultivated from the oral microbiota of Car6(-/-) mice.
      Collective results suggest salivary CA VI may promote caries by modulating the
      oral microbiota to favor S. mutans colonization and/or by the enzymatic
      production of acid within plaque.

PMID- 21945430
TI  - Treatment outcomes between concurrent chemoradiotherapy and combination of
      surgery, radiotherapy, and/or chemotherapy in stage III and IV maxillary sinus
      cancer: multi-institutional retrospective analysis.
AB  - PURPOSE: The incidence of maxillary sinus cancer (MSC) is extremely rare,
      representing less than 1% of all cancers. Because of its rarity, the management
      of locally advanced MSC is a challenging issue. The objective of the present
      study was to retrospectively compare the efficacy of 2 traditional treatment
      strategies, concurrent chemoradiotherapy (CCRT) versus combination of surgery and
      radiotherapy and/or chemotherapy (SRCT) in MSC. PATIENTS AND METHODS: From 1989
      to 2010, 65 patients with histologically confirmed stage III or IVA/IVB were
      retrospectively analyzed. RESULTS: The median age of our subjects was 60 years
      (range 36 to 81). The present study involved 18 women (27.7%) and 47 men (72.3%).
      Of the 65 patients, 52 (80.0%) had squamous cell carcinoma. The TNM stage was
      stage III, as determined by the American Joint Committee on Cancer, 6th edition,
      in 27 patients (41.5%). Stage IVA or IVB was observed in 38 patients (58.5%). Of
      the 65 patients, 41 underwent treatment. Of these 41 patients, 26 and 15 patients
      underwent SRCT and CCRT, respectively. During the 75.6 months (range 6.4 to
      249.4) of median follow-up, the median progression-free survival duration was
      45.1 months (95% confidence interval 0.0 to 142.7). The 5-year overall survival
      rate was 64.8%. However, the patients who had undergone surgery had better
      progression-free survival (hazard ratio 2.363, 95% confidence interval 1.098 to
      5.085, P = .028) and overall survival (hazard ratio 4.989, 95% confidence
      interval 1.646 to 15.118, P = .004). The SRCT group had a better progression-free
      survival (P = .043) and overall survival (P = .029) duration than did the CCRT
      group. CONCLUSION: SRCT might be superior to CCRT for locally advanced MSC.
      Additional studies comparing the treatment outcomes of CCRT with SRCT are
      warranted.

PMID- 21945431
TI  - Delayed translocation of NGFI-B/RXR in glutamate stimulated neurons allows late
      protection by 9-cis retinoic acid.
AB  - Nuclear receptor and apoptosis inducer NGFI-B translocates out of the nucleus as
      a heterodimer with RXR in response to different apoptosis stimuli, and therefore
      represents a potential pharmacological target. We found that the cytosolic levels
      of NGFI-B and RXRalpha were increased in cultures of cerebellar granule neurons
      2h after treatment with glutamate (excitatory neurotransmitter in the brain,
      involved in stroke). To find a time-window for potential intervention the neurons
      were transfected with gfp-tagged expressor plasmids for NGFI-B and RXR. The
      default localization of NGFI-Bgfp and RXRgfp was nuclear, however, translocation
      out of the nucleus was observed 2-3h after glutamate treatment. We therefore
      hypothesized that the time-window between treatment and translocation would allow
      late protection against neuronal death. The RXR ligand 9-cis retinoic acid was
      used to arrest NGFI-B and RXR in the nucleus. Addition of 9-cis retinoic acid 1h
      after treatment with glutamate reduced the cytosolic translocation of NGFI-B and
      RXRalpha, the cytosolic translocation of NGFI-Bgfp observed in live neurons, as
      well as the neuronal death. However, the reduced translocation and the reduced
      cell death were not observed when 9-cis retinoic acid was added after 3h. Thus,
      late protection from glutamate induced death by addition of 9-cis retinoic acid
      is possible in a time-window after apoptosis induction.

PMID- 21945432
TI  - Ultraviolet enhances the sensitivity of pancreatic cancer cells to gemcitabine by
      activation of 5' AMP-activated protein kinase.
AB  - Although gemcitabine is recognized as the standard drug for the treatment of
      advanced pancreatic cancer, the clinical outcome is not satisfactory. We recently
      reported that relatively high dose ultraviolet-C (UV-C; 200J) inhibits cell
      growth by desensitization of epidermal growth factor receptor (EGFR) in human
      pancreatic cancer cells. In the present study, we investigated the combination
      effects of low dose UV-C (10J) and gemcitabine on apoptosis and cell growth in
      these cells. UV-C enhanced gemcitabine-induced suppression of cell viability. In
      addition, the combination use clearly induced apoptosis, while neither UV-C nor
      gemcitabine alone did. Concurrently, combination use caused the decrease in the
      EGFR protein level and reduced EGF-induced activation of Akt pathway,
      subsequently resulting in accumulation of beta-catenin. The order of the
      treatment with UV-C and gemcitabine did not affect their synergistic effects on
      apoptosis and cell growth. Interestingly, combination use synergistically induced
      phosphorylation of 5' AMP-activated protein kinase (AMPK) alpha at Thr172 and
      acetyl-CoA carboxylase at Ser79 as a downstream molecular target of AMPK. AMPK
      activator, 5-aminoimidazole-4-carboxamide-1-beta-riboside, induced apoptosis and
      suppressed cell growth in these cells, thus suggesting that combination effects
      of UV-C and gemcitabine is due to the activation of AMPK. Together, our findings
      could provide a new aspect of pancreatic cancer therapy.

PMID- 21945433
TI  - Noxa induces apoptosis in oncogene-expressing cells through catch-and-release
      mechanism operating between Puma and Mcl-1.
AB  - Tumor suppressor p53 induces apoptosis by transcriptional induction of Noxa and
      Puma, which encode the proapoptotic BH3-only member of the Bcl-2 family proteins.
      In the p53-mediated tumor surveillance system, p53 induces apoptosis or
      replicative senescence in oncogene-expressing cells, resulting in elimination of
      such cells. In this context, we previously found that Noxa and Puma
      synergistically induce apoptosis. Here, we found the adenovirus oncogene E1A to
      induce p53-dependently expression of Puma, but not Noxa. The induced Puma
      associates with antiapoptotic Bcl-2 protein Mcl-1, accompanied by accumulated Mcl
      1 protein on mitochondria. Moreover, E1A also reduces expression of the
      antiapoptotic Bcl-2 protein Bcl-X(L). In contrast, the DNA-damaging agent
      adriamycin induces Noxa expression in E1A-expressing cells. Interestingly, Mcl-1
      knockdown itself induced apoptosis in E1A-expressing MEFs. Furthermore, Noxa
      displaced Puma's association with Mcl-1, accompanied by Mcl-1 degradation and
      apoptosis induction by activating mitochondrial apoptotic executers Bax and Bak.
      These results suggest that p53-induced apoptosis in oncogene-expressing cells is
      regulated by differential induction and sequential activation of Noxa and Puma.
      Accumulated Puma by oncogene enhances susceptibility to apoptosis through "catch"
      in mitochondria by Mcl-1. Subsequently, in response to DNA-damage, Noxa
      efficiently induces apoptosis by "release" of Puma from Mcl-1.

PMID- 21945434
TI  - Crocetin inhibits beta-amyloid fibrillization and stabilizes beta-amyloid
      oligomers.
AB  - Aggregation of a peptide, beta-amyloid (Abeta), is a hallmark molecular process
      found in Alzheimer's disease (AD). During Abeta aggregation, oligomeric and
      fibrillar Abeta are formed, and these molecular self-assembly steps are
      implicated in generation of toxic effects in AD. Crocetin is a natural carotenoid
      dicarboxyl acid displaying various pharmaceutical effects and may be co-localized
      with Abeta mediated by human serum albumin. In the study presented here, we
      examined the effects of crocetin on Abeta aggregation in three different
      molecular pathways. Our results demonstrate that crocetin inhibited Abeta fibril
      formation and destabilized pre-formed Abeta fibrils. Moreover, crocetin caused
      stabilization of Abeta oligomers and prevented their conversion into Abeta
      fibrils. Our study reveals potential pathological and pharmaceutical implication
      of crocetin in AD and suggests possible application of crocetin for currently
      limited structural studies on unstable Abeta oligomers.

PMID- 21945435
TI  - Thyroid hormone differentially modulates Warburg phenotype in breast cancer
      cells.
AB  - Sustenance of cancer cells in vivo critically depends on a variety of genetic and
      metabolic adaptations. Aerobic glycolysis or Warburg effect has been a defining
      biochemical hallmark of transformed cells for more than five decades although a
      clear molecular basis of this observation is emerging only in recent years. In
      this study, we present our findings that thyroid hormone exerts its non-genomic
      and genomic actions in two model human breast cancer cell lines differentially.
      By laying a clear foundation for experimentally monitoring the Warburg phenotype
      in living cancer cells, we demonstrate that thyroid hormone-induced modulation of
      bioenergetic profiles in these two model cell lines depends on the degree of
      Warburg phenotype that they display. Further we also show that thyroid hormone
      can sensitize mitochondria in aggressive, triple-negative breast cancer cells
      favorably to increase the chemotherapeutic efficacy in these cells. Even though
      the role of thyroid hormone in modulating mitochondrial metabolism has been
      known, the current study accentuates the critical role it plays in modulating
      Warburg phenotype in breast cancer cells. The clinical significance of this
      finding is the possibility to devise strategies for metabolically modulating
      aggressive triple-negative tumors so as to enhance their chemosensitivity in
      vivo.

PMID- 21945436
TI  - Protective potential of resveratrol against oxidative stress and apoptosis in
      Batten disease lymphoblast cells.
AB  - Batten disease (BD) is the most common form of a group of disorders called
      neuronal ceroid lipofuscinosis, which are caused by a CLN3 gene mutation. A
      variety of pathogenic lysosomal storage disorder mechanisms have been suggested
      such as oxidative stress, endoplasmic reticulum (ER) stress, and altered protein
      trafficking. Resveratrol, a stilbenoid found in red grape skin, is a potent
      antioxidant chemical. Recent studies have suggested that resveratrol may have a
      curative effect in many neurodegenerative diseases. Therefore, we investigated
      the activities of resveratrol at the levels of oxidative and ER stress and
      apoptosis factors using normal and BD lymphoblast cells. We report that the BD
      lymphoblast cells contained low-levels of superoxide dismutase-1 (SOD-1) due to
      the long-term stress of reactive oxygen species. However, when we treated the
      cells with resveratrol, SOD-1 increased to levels observed in normal cells.
      Furthermore, we investigated the expression of glucose-regulated protein 78 as an
      ER stress marker. BD cells underwent ER stress, but resveratrol treatment
      resolved the ER stress in a dose-dependent manner. We further demonstrated that
      the levels of apoptosis markers such as apoptosis induce factor, cytochrome c,
      and cleavage of poly (ADP)-ribose polymerase decreased following resveratrol
      treatment. Thus, we propose that resveratrol may have beneficial effects in
      patients with BD.

PMID- 21945437
TI  - NKX3.1 contributes to S phase entry and regulates DNA damage response (DDR) in
      prostate cancer cell lines.
AB  - NKX3.1 is an androgen-regulated homeobox gene that encodes a tissue-restricted
      transcription factor, which plays an important role in the differentiation of the
      prostate epithelium. Thus, the role of NKX3.1 as a functional topoisomerase I
      activity enhancer in cell cycle regulation and the DNA damage response (DDR) was
      explored in prostate cancer cell lines. As an early response to DNA damage
      following CPT-11 treatment, we found that there was an increase in the
      gammaH2AX(S139) foci number and that total phosphorylation levels were reduced in
      PC-3 cells following ectopic NKX3.1 expression as well as in LNCaP cells
      following androgen administration. Furthermore, upon drug treatment, the increase
      in ATM(S1981) phosphorylation was reduced in the presence of NKX3.1 expression,
      whereas DNA-PKcs expression was increased. Additionally, phosphorylation of
      CHK2(T68) and NBS1(S343) was abrogated by ectopic NKX3.1 expression, compared
      with the increasing levels in control PC-3 cells in a time-course experiment.
      Finally, NKX3.1 expression maintained a high cyclin D1 expression level
      regardless of drug treatment, while total gammaH2AX(S139) phosphorylation
      remained depleted in PC-3, as well as in LNCaP, cells. Thus, we suggest that
      androgen regulated NKX3.1 maintains an active DDR at the intra S progression and
      contributes to the chemotherapeutic resistance of prostate cancer cells to DNA
      damaging compounds.

PMID- 21945438
TI  - Lectin activity of the nucleocytoplasmic EUL protein from Arabidopsis thaliana.
AB  - The Euonymus lectin (EUL) domain was recognized as the structural motif for a
      novel class of putative carbohydrate binding proteins. Confocal microscopy
      demonstrated that the lectin from Euonymus europaeus (EEA) as well as the EUL
      protein from Arabidopsis thaliana (ArathEULS3) are located in the
      nucleocytoplasmic compartment of the plant cell. ArathEULS3 as well as its EUL
      domain were successfully expressed in Pichia pastoris and purified. The EUL
      domain from Arabidopsis interacts with glycan structures containing Lewis Y,
      Lewis X and lactosamine, indicating that it can be considered a true lectin
      domain. Despite the high sequence identity between the EUL domains in EEA and
      ArathEULS3, both domains recognize different carbohydrate structures.

PMID- 21945440
TI  - Isoliquiritigenin, a chalcone compound, is a positive allosteric modulator of
      GABAA receptors and shows hypnotic effects.
AB  - Isoliquiritigenin (ILTG) is a chalcone compound and has valuable pharmacological
      properties such as antioxidant, anti-inflammatory, anticancer, and antiallergic
      activities. Recently, the anxiolytic effect of ILTG has been reported; however,
      its action mechanism and hypnotic activity have not yet been demonstrated.
      Therefore, we investigated the hypnotic effect and action mechanism of ILTG. ILTG
      significantly potentiated the pentobarbital-induced sleep in mice at doses of 25
      and 50mg/kg. The hypnotic activity of ILTG was fully inhibited by flumazenil
      (FLU), a specific gamma-aminobutyric acid type A (GABA(A))-benzodiazepine (BZD)
      receptor antagonist. The binding affinity of ILTG was 0.453 MUM and was found to
      be higher than that of the reference compound, diazepam (DZP, 0.012 MUM). ILTG
      (10(-5)M) potentiated GABA-evoked currents to 151% of the control level on
      isolated dorsal raphe neurons. ILTG has 65 times higher affinity for GABA(A)-BZD
      receptors than DZP, and the dissociation constant for ILTG was 4.0 * 10(-10)M.
      The effect of ILTG on GABA currents was blocked by 10(-7)M FLU and ZK-93426.
      These results suggest that ILTG produces hypnotic effects by positive allosteric
      modulation of GABA(A)-BZD receptors.

PMID- 21945439
TI  - Development of recombinant Aleuria aurantia lectins with altered binding
      specificities to fucosylated glycans.
AB  - Changes in glycosylation have long been associated with disease. While there are
      many methods to detect changes in glycosylation, plant derived lectins are often
      used to determine changes on specific proteins or molecules of interest. One
      change in glycosylation that has been observed by us and by others is a disease
      or antigen associated increase in fucosylation on N-linked glycans. To measure
      this change, the fucose binding Aleuria aurantia lectin (AAL) is often utilized
      in plate and solution based assays. AAL is a mushroom derived lectin that
      contains five fucose binding sites that preferentially bind fucose linked (alpha
      1,3, alpha-1,2, alpha-,4, and alpha-1,6) to N-acetyllactosamine related
      structures. Recently, several reports by us and by others have indicated that
      specific fucose linkages found on certain serum biomarker glycoprotein's are more
      associated with disease than others. Taking a site-directed mutagenesis approach,
      we have created a set of recombinant AAL proteins that display altered binding
      affinities to different analytes containing various fucose linkages.

PMID- 21945441
TI  - Functional relationship between Claspin and Rad17.
AB  - Claspin was originally identified as a Check1 (Chk1)-interacting protein. Claspin
      and Rad17 are reportedly involved in the DNA damage-induced phosphorylation of
      Chk1, a hallmark of checkpoint activation. To understand the cellular functions
      of Claspin and the functional relationship between Claspin and Rad17, we
      generated Claspin(-/-) and Claspin(-/-)/RAD17(-) cells using chicken DT40 cells,
      which contain an exogenously introduced Claspin that can be suppressed by the
      addition of doxycycline (Dox). In the presence of Dox, Claspin(-/-) cells ceased
      growth within 2 days, leading to cell death. In addition, a remarkable reduction
      in the rate of DNA elongation was observed in Claspin-depleted cells, suggesting
      that Claspin plays a critical role in DNA replication in the absence of exogenous
      stress. When cells were exposed to methyl methanesulfonate (MMS), a DNA damaging
      agent, RAD17(-) cells showed a greater defect in checkpoint activation than
      Claspin(-/-) cells as monitored by progression of cell cycle and phosphorylation
      of Chk1. Knocking out RAD17 gene showed almost no additive effects on cell death
      and DNA elongation rates in Claspin-depleted cells.

PMID- 21945442
TI  - Neurotensin-induced Erk1/2 phosphorylation and growth of human colonic cancer
      cells are independent from growth factors receptors activation.
AB  - Neurotensin (NT) promotes the proliferation of human colonic cancer cells by
      undefined mechanisms. We already demonstrated that, in the human colon
      adenocarcinoma cell line HT29, the effects of NT were mediated by a complex
      formed between the NT receptor-1 (NTSR1) and-3 (NTSR3). Here we examined cellular
      mechanisms that led to NT-induced MAP kinase phosphorylation and growth factors
      receptors transactivation in colonic cancer cells and proliferation in HT29
      cells. With the aim to identify upstream signaling involved in NT-elicited MAP
      kinase activation, we found that the stimulatory effects of the peptide were
      totally independent from the activation of the epidermal growth factor receptor
      (EGFR) both in the HT29 and the HCT116 cells. NT was unable to promote
      phosphorylation of EGFR and to compete with EGF for its binding to the receptor.
      Pharmacological approaches allowed us to differentiate EGF and NT signaling in
      HT29 cells since only NT activation of Erk1/2 was shown to be sensitive to PKC
      inhibitors and since only NT increased the intracellular level of calcium. We
      also observed that NT was not able to transactivate Insulin-like growth factor
      receptor. Our findings indicate that, in the HT29 and HCT116 cell lines, NT
      stimulates MAP kinase phosphorylation and cell growth by a pathway which does not
      involve EGF system but rather NT receptors which transduce their own
      intracellular effectors. These results indicate that depending on the cell line
      used, blocking EGFR is not the general rule to inhibit NT-induced cancer cell
      proliferation.

PMID- 21945443
TI  - Characterization of an AtCCX5 gene from Arabidopsis thaliana that involves in
      high-affinity K+ uptake and Na+ transport in yeast.
AB  - The gene for a putative cation calcium exchanger (CCX) from Arabidopsis thaliana,
      AtCCX5, was cloned and its function was analyzed in yeast. Green fluorescent
      protein-tagged AtCCX5 expressed in yeast was localized in the plasma membrane and
      nuclear periphery. The yeast transformants expressing AtCCX5 were created and
      their growth in the presence of various cations (K(+), Na(+), Ca(2+), Mg(2+),
      Fe(2+), Cu(2+), Co(2+), Cd(2+), Mn(2+), Ba(2+), Ni(2+), Zn(2+), and Li(+)) were
      analyzed. AtCCX5 expression was found to affect the response to K(+) and Na(+) in
      yeast. The AtCCX5 transformant also showed a little better growth to Zn(2+). The
      yeast mutant 9.3 expressing AtCCX5 restored growth of the mutant on medium with
      low K(+) (0.5mM), and also suppressed its Na(+) sensitivity. Ion uptake
      experiments showed that AtCCX5 mediated relatively high-affinity K(+) uptake and
      was also involved in Na(+) transport in yeast. Taken together, these findings
      suggest that the AtCCX5 is a novel transport protein involves in mediating high
      affinity K(+) uptake and Na(+) transport in yeast.

PMID- 21945444
TI  - Semaphorin 3A lytic hybrid peptide binding to neuropilin-1 as a novel anti-cancer
      agent in pancreatic cancer.
AB  - We previously reported that novel targeted "hybrid peptide" in which epidermal
      growth factor receptor (EGFR) binding peptide was conjugated with lytic-type
      peptide had selective cytotoxic activity to EGFR expressing cancer cells. In this
      study, we have generated a novel type hybrid peptide, semaphorin 3A lytic (Sema3A
      lytic), which is composed of two functional amino acid domains: a sequence
      derived from Sema3A that binds to neuropilin-1 (NRP1) and a cytotoxic lytic
      peptide. We found that this hybrid peptide had cytotoxic activity against NRP1
      positive pancreatic cancer cell lines such as BxPC-3 and Panc-1, whereas the
      peptide did not affect the viability of normal cells in vitro. It was also found
      by affinity analysis that Sema3A peptide binds to NRP1, and two arginines (372R
      and 377R) in Sema3A peptide are involved in the interaction with NRP1 protein. In
      addition, confocal microscopy analysis revealed that Sema3A-lytic peptide could
      not penetrate normal cells regardless of the presence of NRP1 mRNA, suggesting
      that the ability of Sema3A-lytic peptide to concentrate adjacent to the cell
      membrane by binding to NRP1 with the target-binding moiety contributes to its
      selective cytotoxic activity. These results indicate that Sema3A-lytic hybrid
      peptide would be a possible anti-cancer agent for treatment of human pancreatic
      cancer.

PMID- 21945446
TI  - Critical role of type 1 plasminogen activator inhibitor (PAI-1) in early host
      defense against nontypeable Haemophilus influenzae (NTHi) infection.
AB  - Respiratory systems are constantly being challenged by pathogens. Lung epithelial
      cells serve as a first line of defense against microbial pathogens by detecting
      pathogen-associated molecular patterns (PAMPs) and activating downstream
      signaling pathways, leading to a plethora of biological responses required for
      shaping both the innate and adaptive arms of the immune response. Acute-phase
      proteins (APPs), such as type 1 plasminogen activator inhibitor (PAI-1), play
      important roles in immune/inflammatory responses. PAI-1, a key regulator for
      fibrinolysis and coagulation, acts as an APP during acute phase response (APR)
      such as acute lung injury (ALI), inflammation, and sepsis. However, the role of
      PAI-1 in the pathogenesis of these diseases still remains unclear, especially in
      bacterial pneumonia. In this study, we showed that PAI-1 expression is
      upregulated following nontypeable Haemophilus influenzae (NTHi) infection. PAI-1
      knockout (KO) mice failed to generate early immune responses against NTHi.
      Failure of generating early immune responses in PAI-1 KO mice resulted in reduced
      bacterial clearance and prolonged disease process, which in turn led to enhanced
      inflammation at late stage of infection. Moreover, we also found that NTHi
      induces PAI-1 via activation of TLR2-MyD88-MKK3-p38 MAPK signaling pathway. These
      data suggest that PAI-1 plays critical role in earl host defense response against
      NTHi infection. Our study thus reveals a novel role of PAI-1 in infection caused
      by NTHi, one of the most common gram-negative bacterial pathogens in respiratory
      systems.

PMID- 21945447
TI  - Arsenic-contaminated cold-spring water in mountainous areas of Hui County,
      Northwest China: a new source of arsenic exposure.
AB  - Although pump-well is the primary drinking water source in rural areas of China,
      there are still 8.4% of villages reliant on cold-spring. In this study, a survey
      of arsenic concentration in cold-springs and pump-wells was carried out in Hui
      County, Northwest China. A total of 352 drinking water samples, including 177
      cold-springs and 175 pump-wells, were collected. The maximum arsenic
      concentrations in cold-springs and pump-wells were 0.482 mg/L and 0.067 mg/L,
      respectively. We found that 15.8% (28) of total cold-springs and 1.1% (2) of
      total pump-wells had arsenic concentrations exceeding the maximum allowable
      concentration of arsenic in drinking water of rural China (0.05 mg/L). Our
      findings show that 5 cold spring-contaminated villages are located in the
      mountainous areas of Hui County and 2224 inhabitants may be at risk of high
      arsenic exposure. This paper indicates that arsenic contamination of cold-springs
      may be more serious than expected in mountainous areas of Northwest China and
      extensive surveys and epidemiological studies should be carried out to
      investigate the potential contaminated areas and affected population.

PMID- 21945445
TI  - HIV-1 envelope protein gp120 up regulates CCL5 production in astrocytes which can
      be circumvented by inhibitors of NF-kappaB pathway.
AB  - HIV associated neurological disorders (HAND) is a common neurological
      complication in patients infected with HIV. The proinflammatory cytokines and
      chemokines produced by astrocytes play a pivotal role in neuroinflammatory
      processes in the brain and viral envelope gp120 has been implicated in this
      process. In view of increased levels of CCL5 observed in the CSF of HIV-1
      infected patients, we studied the effects of gp120 on CCL5 expression in
      astrocytes and the possible mechanisms responsible for those effects.
      Transfection of the SVGA astrocyte cell line with a plasmid encoding gp120
      resulted in a time-dependent increase in expression levels of CCL5 in terms of
      mRNA and protein by 24.6 +/- 2.67- and 35.2 +/- 6.1-fold, respectively. The
      fluorescent images showed localization of CCL5 in the processes of the
      astrocytes. The gp120-specific siRNA abrogated the gp120-mediated increase in
      CCL5 expression. We also explored a possible mechanism for the effects of gp120
      on CCL5 expression. Using a specific inhibitor for the NF-kappaB pathway, we
      demonstrated that levels of gp120 induction of CCL5 expression can be abrogated
      by 44.6 +/- 4.2% at the level of mRNA and 51.8 +/- 5.0% at the protein level.
      This was further confirmed by knocking down NF-kappaB through the use of siRNA.

PMID- 21945448
TI  - In vitro evaluation of the erosive potential of orange juice modified by food
      additives in enamel and dentine.
AB  - OBJECTIVES: To evaluate the erosive potential of orange juice modified by food
      additives in enamel and dentine. METHODS: Calcium lactate pentahydrate (CLP),
      xanthan gum (XG), sodium linear polyphosphate (LPP), sodium pyrophosphate
      tetrabasic (PP), sodium tripolyphosphate (STP) and some of their combinations
      were added to an orange juice. Pure orange juice and a calcium-modified juice
      were used as negative (C-) and positive (C+) controls, respectively. In phase 1,
      15 modified orange juices were tested for erosive potential using pH-stat
      analysis. In phase 2, the additives alone and the combination with good results
      in phase 1 and in previous studies (CLP+LPP) were tested in an erosion
      remineralization cycling model. In phase 3, the erosion and remineralization
      episodes were studied independently. Enamel was analysed by surface microhardness
      (SMH) and profilometry, whilst dentine by profilometry. RESULTS: In phase 1,
      reduction of the erosive potential was observed for all additives and their
      combinations, except XG alone. In phase 2, no detectable enamel loss was observed
      when CLP, LPP and CLP+LPP were added to the juice. XG, STP and PP had enamel loss
      similar to C- (p>0.05). Amongst additives, the combination CLP+LPP showed the
      highest SMH values followed by CLP (p<0.05). All the other groups presented SMH
      values similar to C- (p>0.05). For dentine, only CLP+LPP lead to surface loss
      values lower than C- (p<0.05). In phase 3, CLP, LPP and CLP+LPP seemed to protect
      against erosion; whilst none of the tested compounds seemed to interfere with the
      remineralization process. CONCLUSIONS: CLP and LPP reduced erosion on enamel and
      this effect was enhanced by their combination. For dentine, only the combination
      CLP+LPP reduced erosion.

PMID- 21945449
TI  - Microhardness and chemical analysis of high-viscous glass-ionomer cement after 10
      years of clinical service as ART restorations.
AB  - OBJECTIVES: The aim of this study was to evaluate the Knoop microhardness (KHN)
      and chemical composition of high-viscous glass-ionomer cement (HVGIC) after 10
      years of clinical service. METHODS: Six HVGIC samples were cut from 10-year ART
      restorations. The sections were embedded in acrylic moulds with their
      longitudinal profile exposed. KHN was determined by performing three sequences of
      five indentations at 10, 30, 50, 70 and 90 MUm of HVGIC outer surface. For the
      control group (n=6), HVGIC specimens were stored in distilled water for 24
      months. Hardness measurements were taken at days 7, 30, 60, 120, 180, 360, and
      720. For chemical analysis using SEM-EDX, 10-year and control specimens were
      dehydrated and coated with carbon. Data were analysed using T-test and
      ANOVA/Tukey's test (p<0.05). RESULTS: A significant KHN increase was observed in
      the control group up to the 180-day period. From this point the values stabilized
      and no more significant differences were found between the 10-year and the
      control KHN values. No statistical differences were observed amongst the KHN from
      inner distances compared to the outer surface of the 10-year HVGIC specimens. In
      one 10-year specimen, SEM-images identified the transformation of HVGIC in an
      altered layer with no glass filler particles detectable, and raised Ca, K and P
      contents. CONCLUSIONS: KHN values of ten-year HVGIC specimens were similar to the
      control group values at 180-day storage period. Except for one 10-year specimen
      in that an altered layer could be seen, chemical composition was similar amongst
      the depths evaluated.

PMID- 21945450
TI  - The organization of honeybee ocelli: Regional specializations and rhabdom
      arrangements.
AB  - We have re-investigated the organization of ocelli in honeybee workers and
      drones. Ocellar lenses are divided into a dorsal and a ventral part by a cusp
      shaped indentation. The retina is also divided, with a ventral retina looking
      skywards and a dorsal retina looking at the horizon. The focal plane of lenses
      lies behind the retina in lateral ocelli, but within the dorsal retina in the
      median ocellus of both workers and drones. Ventral retinula cells are ca. 25MUm
      long with dense screening pigments. Dorsal retinula cells are ca. 60MUm long with
      sparse pigmentation mainly restricted to their proximal parts. Pairs of retinula
      cells form flat, non-twisting rhabdom sheets with elongated, straight,
      rectangular cross-sections, on average 8.7MUm long and 1MUm wide. Honeybee
      ocellar rhabdoms have shorter and straighter cross-sections than those recently
      described in the night-active bee Megalopta genalis. Across the retina, rhabdoms
      form a fan-shaped pattern of orientations. In each ocellus, ventral and dorsal
      retinula cell axons project into two separate neuropils, converging on few large
      neurons in the dorsal, and on many small neurons in the ventral neuropil. The
      divided nature of the ocelli, together with the particular construction and
      arrangement of rhabdoms, suggest that ocelli are not only involved in attitude
      control, but might also provide skylight polarization compass information.

PMID- 21945452
TI  - Quantitative determination of rhein in human plasma by liquid chromatography
      negative electrospray ionization tandem mass/mass spectrometry and the
      application in a pharmacokinetic study.
AB  - To investigate the pharmacokinetics of rhein in human, a liquid chromatography
      electrospray ionization tandem mass/mass spectrometry (HPLC-ESI-MS/MS) method for
      the determination of rhein in human plasma is established in this study.
      Indomethacin is used as the internal standard (I.S.). The plasma samples are
      analyzed after protein precipitation with methanol, and the LC separation is
      performed on an Agilent Eclipse XDB-C18 column with a mobile phase of
      acetonitrile-0.2% formic acid water (70:30, v/v). The electrospray-ion source is
      performed in the negative mode. The multi-reaction monitoring mode is selected
      and the ion selected channels are set at m/z: 283.1->238.9 for rhein ([M-H](-)
      >[M-CO(2)-H](-)) and m/z: 356.2->312.0 for indomethacin ([M-H](-)->[M-CO(2)-H](
      )), respectively. Calibration curve is linear over the range of 1.0-8000.0ng/ml.
      The chromatographic separation is achieved within 12min. The lower limits of
      quantification (LLOQ) is 1.0ng/ml. The intra- and inter-run precisions are less
      than 4.65% and 8.28%, respectively. The method is successfully applied to
      determine the plasma concentrations of rhein in Chinese volunteers.

PMID- 21945451
TI  - Depressive phenotypes evoked by experimental diabetes are reversed by insulin.
AB  - Clinical studies suggest a bidirectional relationship between diabetes and
      depression, where diabetes may increase risk for depressive symptoms and
      depression may increase risk for diabetes. Preclinical models examining the
      effects of diabetes on brain and behavior can provide insights to the
      pathophysiology underlying this relationship. The current study comprehensively
      examined, in C57BL/6 mice, the development of depressive phenotypes evoked by
      diabetes induced by streptozotocin (STZ) and determined if insulin treatment was
      able to reverse the diabetes-related changes on brain and affective behavior.
      Since anxiety is often comorbid with mood disturbances, behavioral tests for both
      anxiety and depression were administered. Possible physiological correlates of
      behavioral changes, including hippocampal cell proliferation, brain derived
      neurotrophic factor, and plasma corticosterone, were also measured. STZ-induced
      diabetes resulted in increased immobility in the tail suspension test, increased
      intracranial self-stimulation thresholds, decreased hippocampal cell
      proliferation, and increased corticosterone levels. Insulin treatment, on the
      other hand, reduced hyperglycemia, reversed the behavioral effects, and returned
      hippocampal cell proliferation and corticosterone to levels comparable to the
      control group. Anxiety-related behaviors were unaffected. This study showed that
      experimental diabetes in the mouse produced depressive phenotypes that were
      reversed by insulin therapy. Changes in reward-related behaviors and hippocampal
      cell proliferation may be useful markers to identify therapeutic interventions
      for comorbid diabetes and depression.

PMID- 21945453
TI  - Estimation of the lipophilic character of flavonoids from the retention behavior
      in reversed phase liquid chromatography on different stationary phases: A
      comparative study.
AB  - The retention behavior of some flavonoids in reversed phase liquid chromatography
      (RPLC) was investigated using different chemistries of the modified silicagel
      based stationary phases. Highly end-capped octadecyl silicagel (ODS), polar
      embedded linker octadecyl silicagel (SB-18 Aqua), phenyl silicagel and
      pentafluorophenyl modified silicagel (PFP) were used as stationary phases. The
      mobile phase consisted in acetonitrile/acidified water mixtures, at different
      fractions of volume. The lipophilicity was estimated through different
      chromatographic descriptors, as it follows: log k(w), m log k, S, phi(0) and
      PC1/log k. The chromatographic behavior observed on the mentioned stationary
      phases was evaluated by means of various graphical profiles and correlation
      matrices. Additionally, new information about the characteristics of the
      stationary phases and their (dis)-similarities were provided through
      lipophilicity charts and by scatterplots of loadings obtained by applying
      principal component analysis (PCA) to retention data. Furthermore, the
      experimental lipophilicity indices estimated from retention data were correlated
      with the computed descriptors, at a high level of statistical significance.

PMID- 21945454
TI  - Re "Nutritional risk factors for development of postpartum prediabetes and
      diabetes in women with gestational diabetes mellitus" by Kim et al.

PMID- 21945455
TI  - Glutathione metabolism is modulated by postmortem interval, gender difference and
      agonal state in postmortem human brains.
AB  - The equilibrium between antioxidant function and oxidative stress is implicated
      in brain pathology. However, human studies on oxidant and antioxidant markers
      rely on postmortem tissue that might be affected by pre and postmortem factors.
      To evaluate the effect of these variables, we tested whether antioxidant enzymes
      [superoxide dismutase (SOD), catalase] glutathione (GSH) and related enzymes
      [gamma glutamylcysteine ligase (GCL), GSH peroxidase (GPx), GSH reductase (GR),
      GSH-S-transferase (GST)] and malondialdehyde (MDA, marker of lipid peroxidation)
      are affected in postmortem human brains (n=50) by increase in postmortem interval
      (2.5-26 h), gender difference and agonal state [based on Glasgow coma scale
      (GCS): range: 3-15] in different anatomical regions-frontal cortex (FC),
      cerebellum (CB) medulla oblongata (MO), substantia nigra (SN) and hippocampus
      (HC). While SOD and catalase activities were relatively unaltered, GR and GPx
      activities were affected by agonal state (GR in CB, p<0.05; GPx in MO, p<0.05)
      indicating altered GSH dynamics during the secondary events following neuronal
      injury. MO, SN and HC displayed low GSH compared to FC and CB. Total GSH level
      was decreased with PMI (MO, p=0.02) which could be partly attributed to increase
      in MDA levels with increasing PMI in MO (p<0.05). Total GSH level was higher in
      CB (p<0.017) and MO (p<0.04) in female brains compared to males. Interestingly,
      HC and SN regions showed significant stability in most of the markers tested. We
      suggest that while SOD and catalase were relatively unaffected by the pre and
      postmortem factors, GSH and its metabolic enzymes were significantly altered and
      this was more pronounced in MO of postmortem human brains. These data highlight
      the influence of pre and postmortem factors on GSH dynamics and the inherent
      differences in brain regions, with implications for studies on brain
      pathophysiology employing human samples.

PMID- 21945456
TI  - Persistence of locomotor-related interlimb reflex networks during walking after
      stroke.
AB  - OBJECTIVE: Cutaneous nerve stimulation evokes coordinated and phase-modulated
      reflex output widely distributed to muscles of all four limbs during walking.
      Accessibility to this distributed network after stroke offers insight into the
      pathological changes and suggests utility for therapeutic applications. Here we
      examined muscles in both the more (MA) and less affected (LA) legs evoked by
      stimulation at the ankle and wrist during walking in chronic (>6 months post CVA)
      stroke. METHODS: Stroke and control participants walked on a treadmill with a
      harness support system. Reflexes were evoked with trains of electrical stimuli
      delivered separately to the cutaneous superficial peroneal (SP; at the ankle) and
      superficial radial (SR; at the wrist) nerves. Background locomotor and reflex EMG
      were phase-averaged across the gait cycle and analyzed off line. RESULTS:
      Locomotor background muscle activation patterns were altered bilaterally in
      stroke, as compared with control. Phase-dependent modulation of interlimb
      cutaneous reflexes was found in both stroke and control subjects with stimulation
      of each nerve, but responses were blunted in stroke. Reflex reversal in tibialis
      anterior (TA) at heel strike with SP nerve stimulation was present in both
      groups. Notably, SR nerve stimulation produced facilitation during the swing-to
      stance transition in the TA and suppression of MG in the MA leg during stance.
      CONCLUSIONS: Interlimb cutaneous inputs may access coordinated reflex pathways in
      the MA limb during walking after stroke. Importantly activation in these pathways
      could provoke responses to counter foot drop during swing phase of walking.
      Additionally, our data support the perspective that there is no "unaffected" side
      after stroke and that caution should be used when interpreting the LA side as
      "control" after stroke. SIGNIFICANCE: The presence of functionally-relevant
      interlimb cutaneous reflexes in the MA leg presents a substrate that may be
      strengthened by rehabilitation.

PMID- 21945457
TI  - Early, severe and bilateral loss of LTP and LTD-like plasticity in motor cortex
      (M1) in de novo Parkinson's disease.
AB  - OBJECTIVE: To test the plasticity of bilateral motor cortices (M1) in treatment
      naive (de novo) Parkinson's disease (PD) patients and its response to single dose
      of L-DOPA. METHODS: Twenty-one de novo PD patients with only unilateral motor
      symptoms were recruited to eliminate the effects of advanced disease and chronic
      treatment and were tested with intermittent (n=10) and continuous theta burst
      stimulation (iTBS and cTBS) (n=11) protocols to induce LTP and LTD-like
      plasticity on both M1 cortices. They were compared with two groups of 10 each,
      age-matched, healthy volunteers (HV). Severity of motor signs and effectiveness
      of TBS were measured bilaterally in the untreated state and after a uniform dose
      of L-DOPA in all patients. RESULTS: iTBS and cTBS induced significant LTP and LTD
      like plasticity in M1 of HV. In de novo patients, there was no plasticity in
      both M1. Acute L-DOPA challenge did not improve plasticity in either M1 cortices,
      though motor signs of PD improved. There was no correlation of motor signs with
      M1 plasticity. CONCLUSION: The early, severe and bilateral loss of plasticity in
      M1 in de novo PD patients is a primary disease-related cortical dysfunction. The
      contrasting L-DOPA response of motor signs and M1 plasticity could arise from
      differences in neural circuits mediating them or differing effects of acute
      dopamine replacement on circuits recruited by specific plasticity-induction
      techniques, particularly in treatment naive PD. SIGNIFICANCE: M1 plasticity
      defect occurs early in PD and might affect motor learning. Acute vs. chronic
      dopamine replacement could have different effects on plasticity in PD or in the
      networks recruited by a specific plasticity induction technique.

PMID- 21945458
TI  - Sodium dl-alpha-tocopheryl-6-O-phosphate inhibits PGE2 production in
      keratinocytes induced by UVB, IL-1beta and peroxidants.
AB  - The water-soluble vitamin E derivative, sodium dl-alpha-tocopheryl-6-O-phosphate
      (1), exhibits protective effects against skin damage. As reported herein, we
      investigated the actions of 1 on the formation of the inflammatory mediator,
      prostaglandin E(2) (PGE(2)), as compared to dl-alpha-tocopheryl acetate (2) and
      dipotassium glycyrrhizin acid (3). In a three-dimensional (3D) human skin model 1
      was converted to alpha-tocopherol (Toc) to a greater extent than 2. Post
      treatment using 2% 1 following ultraviolet B (UVB) irradiation for 2h
      significantly reduced photodamage as indicated by UVB-damaged cell formation and
      PGE(2) synthesis. In normal human epidermal keratinocytes stimulated with UVB
      irradiation, or exposed to interleukin-1 beta, tert-butylhydroperoxide or
      hydrogen peroxide, pre-treatment with 1 (0-2 MUM) inhibited PGE(2) production in
      dose-dependent manner to a greater extent than 2 and 3. Increases in stimulator
      induced cyclooxygenase 2 mRNA expression and p38 MAPK phosphorylation were
      suppressed by pre-treatment with 1. The vitamin C derivative, magnesium L
      ascorbyl-2-phosphate, significantly and synergistically, enhanced the inhibitory
      effects of 1 on PGE(2) production. These results suggest that 1 is a highly
      potent protective when compared among the examined commercial human skin care
      products, and that it might be useful for therapeutic and preventive medicine.

PMID- 21945459
TI  - Is your nursing home a battlefield?

PMID- 21945460
TI  - The omega-6/omega-3 ratio is of importance!

PMID- 21945461
TI  - Spectroscopic characterization of Coomassie blue and its binding to amyloid
      fibrils.
AB  - Coomassie brilliant blue G-250 (CB) is the dye used frequently in the Bradford
      assay for protein concentration determination. In this study, we investigated how
      the solvent polarity and viscosity affect the CB absorption and fluorescence
      spectra and apply this understanding to investigate the binding of CB to lysozyme
      and insulin in the native and amyloid fibril states. Coomassie blue binds both to
      the native protein and to amyloid fibrils but gives distinctly different spectral
      responses. The absorption and fluorescence spectra of CB indicate that binding
      sites in the fibrils are less polar and hold the CB dye more rigidly than in the
      native forms. The spectral comparison of CB bound to the two different fibrils
      showed that the binding sites are different, and this was most likely due to
      differences in secondary structure as monitored by circular dichroism. Finally,
      linear dichroism was used to show that the fibril-bound CB is oriented
      preferentially parallel to the insulin amyloid fibril axis.

PMID- 21945462
TI  - Blood-brain barrier permeability derangements in posterior circulation ischemic
      stroke: frequency and relation to hemorrhagic transformation.
AB  - BACKGROUND: Early disruption of the blood-brain barrier (BBB) due to severe
      ischemia can be detected by MRI T2* permeability imaging. In middle cerebral
      artery (MCA) infarction, pretreatment T2* permeability derangements have been
      found in 22% of patients and are powerful predictors of hemorrhagic
      transformation after revascularization therapy. The frequency, clinical
      correlates, and relation to hemorrhagic transformation of permeability
      derangements in posterior circulation have not been previously explored, and may
      differ as ischemia volume and collateral status are different between
      vertebrobasilar and MCA infarcts. METHODS: We analyzed clinical and pretreatment
      MRI data on consecutive patients undergoing recanalization therapy for acute
      vertebrobasilar ischemia at a medical center November 2001 through September
      2009. Pretreatment MRI permeability images were derived from perfusion source
      imaging acquisitions. Permeability abnormality was detected as persisting
      increased signal intensity at later time points in perfusion MRI acquisition,
      indicating local accumulation of contrast caused by BBB leakage. RESULTS: Among
      the 14 patients meeting study entry criteria, mean age was 71.1 years and median
      pretreatment NIHSS was 20.5. Permeability imaging abnormality was present in 1 of
      the 14 patients (7%). Among 14 patients, post-treatment parenchymal hematoma
      occurred in one and more minor degrees of hemorrhagic transformation in four. The
      one patient with pretreatment permeability abnormality was the patient to develop
      post-treatment parenchymal hematoma (Fisher's exact test, P=0.07). CONCLUSION:
      Pretreatment permeability abnormality, an indicator of BBB derangements, is an
      infrequent finding in acute posterior circulation ischemic stroke and may be
      associated with an increased risk of parenchymal hematoma development undergoing
      recanalization therapy.

PMID- 21945463
TI  - Synthesis and anticancer activity of 5'-chloromethylphosphonates of 3'-azido-3'
      deoxythymidine (AZT).
AB  - A series of novel N-alkyl 5'-chloromethylphosphonates of 3'-azido-3'
      deoxythymidine (6-15) was synthesized by means of phosphonylation of 3'-azido-3'
      deoxythymidine (4) with P-chloromethylphosphonic ditriazolide (3) followed by a
      reaction with the appropriate amine. The synthesized phosphonamidates 6-15 were
      evaluated for their cytotoxic activity in two human cancer cell lines: oral (KB)
      and breast (MCF-7) using the sulforhodamine B (SRB) assay. The highest activity
      in KB human cancer cells was displayed by phosphonamidate 8 (IC(50)=5.8 MUg/mL),
      however, this compound was less potent than the parent AZT (IC(50)=3.1 MUg/mL).
      Phosphonamidate 10 showed only moderate activity (IC(50)=12.1 MUg/mL) whereas the
      other phosphonamidates proved inactive. Similarly, the highest activity in MCF-7
      human cancer cells was displayed by phosphonamidate 8 (IC(50)=3.7 MUg/mL) but it
      proved somewhat less active than AZT (IC(50)=2.6 MUg/mL). Some activity was also
      displayed by phosphonamidate 10 (IC(50)=12.8 MUg/mL) but the other
      phosphonamidates were found inactive. Hydrolysis studies indicate that the
      synthesized phosphonamidates are likely to act as prodrugs of the parent
      nucleoside (AZT). Transport measurements showed that the most active
      phosphonamidates (8 and 10) were able to permeate across the intestinal
      epithelium in vitro. The apparent permeability coefficients determined in Caco-2
      cell monolayers indicated that these compounds could be moderately absorbed in
      humans.

PMID- 21945464
TI  - Sub-cellular targeting of constitutive NOS in health and disease.
AB  - Constitutive nitric oxide synthases (NOSs) are ubiquitous enzymes that play a
      pivotal role in the regulation of myocardial function in health and disease. The
      discovery of both a neuronal NOS (nNOS) and an endothelial NOS (eNOS) isoform in
      the myocardium and the availability of genetically modified mice with selective
      eNOS or nNOS gene deletion have been of crucial importance for understanding the
      role of constitutive nitric oxide (NO) production in the myocardium. eNOS and
      nNOS are homologous in structure and utilize the same co-factors and substrates;
      however, they differ in their subcellular localization, regulation, and
      downstream signaling, all of which may account for their distinct effects on
      excitation-contraction coupling. In particular, eNOS-derived NO has been reported
      to increase left ventricular (LV) compliance, attenuate beta-adrenergic inotropy
      and enhance parasympathetic/muscarinic responses, and mediate the negative
      inotropic response to beta3 adrenoreceptor stimulation via cGMP-dependent
      signaling. Conversely, nNOS-derived NO regulates basal myocardial inotropy and
      relaxation by inhibiting the sarcolemmal Ca(2+) current (I(Ca)) and promoting
      protein kinase A-dependent phospholamban (PLN) phosphorylation, independent of
      cGMP. By inhibiting the activity of myocardial oxidase systems, nNOS regulates
      the redox state of the myocardium and contributes to maintain eNOS "coupled"
      activity. After myocardial infarction, up-regulation of myocardial nNOS
      attenuates adverse remodeling and prevents arrhythmias whereas uncoupled eNOS
      activity in murine models of left ventricular pressure overload accelerates the
      progress towards heart failure. Here we review the evidence in support of the
      idea that NOS subcellular localization, mode of activation, and downstream
      signaling account for the diverse and highly specialized actions of NO in the
      heart. This article is part of a Special Issue entitled "Local Signaling in
      Myocytes".

PMID- 21945465
TI  - Self-organised transients in a neural mass model of epileptogenic tissue
      dynamics.
AB  - Stimulation of human epileptic tissue can induce rhythmic, self-terminating
      responses on the EEG or ECoG. These responses play a potentially important role
      in localising tissue involved in the generation of seizure activity, yet the
      underlying mechanisms are unknown. However, in vitro evidence suggests that self
      terminating oscillations in nervous tissue are underpinned by non-trivial spatio
      temporal dynamics in an excitable medium. In this study, we investigate this
      hypothesis in spatial extensions to a neural mass model for epileptiform
      dynamics. We demonstrate that spatial extensions to this model in one and two
      dimensions display propagating travelling waves but also more complex transient
      dynamics in response to local perturbations. The neural mass formulation with
      local excitatory and inhibitory circuits, allows the direct incorporation of
      spatially distributed, functional heterogeneities into the model. We show that
      such heterogeneities can lead to prolonged reverberating responses to a single
      pulse perturbation, depending upon the location at which the stimulus is
      delivered. This leads to the hypothesis that prolonged rhythmic responses to
      local stimulation in epileptogenic tissue result from repeated self-excitation of
      regions of tissue with diminished inhibitory capabilities. Combined with previous
      models of the dynamics of focal seizures this macroscopic framework is a first
      step towards an explicit spatial formulation of the concept of the epileptogenic
      zone. Ultimately, an improved understanding of the pathophysiologic mechanisms of
      the epileptogenic zone will help to improve diagnostic and therapeutic measures
      for treating epilepsy.

PMID- 21945466
TI  - MRI signature in a novel mouse model of genetically induced adult oligodendrocyte
      cell death.
AB  - Two general pathological processes contribute to multiple sclerosis (MS): acute
      inflammation and degeneration. While magnetic resonance imaging (MRI) is highly
      sensitive in detecting abnormalities related to acute inflammation both
      clinically and in animal models of experimental autoimmune encephalomyelitis
      (EAE), the correlation of these readouts with acute and future disabilities has
      been found rather weak. This illustrates the need for imaging techniques
      addressing neurodegenerative processes associated with MS. In the present work we
      evaluated the sensitivity of different MRI techniques (T(2) mapping, macrophage
      tracking based on labeling cells in vivo by ultrasmall particles of iron oxide
      (USPIO), diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI))
      to detect histopathological changes in a novel animal model making use of
      intrinsic, temporally and spatially controlled triggering of oligodendrocyte cell
      death. This mouse model allows studying the MRI signature associated to
      neurodegenerative processes of MS in the absence of adaptive inflammatory
      components that appear to be foremost in the EAE models. Our results revealed
      pronounced T(2) hyperintensities in brain stem and cerebellar structures, which
      we attribute to structural alteration of white matter by pronounced vacuolation.
      Brain areas were found devoid of significant macrophage infiltration in line with
      the absence of a peripheral inflammatory response. The significant decrease in
      diffusion anisotropy derived from DTI measures in these structures is mainly
      caused by a pronounced decrease in diffusivity parallel to the fiber indicative
      of axonal damage. Triggering of oligodendrocyte ablation did not translate into a
      significant increase in radial diffusivity. Only minor decreases in MT ratio have
      been observed, which is attributed to inefficient removal of myelin debris.

PMID- 21945467
TI  - Contralateral white noise attenuates 40-Hz auditory steady-state fields but not
      N100m in auditory evoked fields.
AB  - The different response characteristics of the different auditory cortical
      responses under conventional central masking conditions were examined by
      comparing the effects of contralateral white noise on the cortical component of
      40-Hz auditory steady state fields (ASSFs) and the N100 m component in auditory
      evoked fields (AEFs) for tone bursts using a helmet-shaped magnetoencephalography
      system in 8 healthy volunteers (7 males, mean age 32.6 years). The ASSFs were
      elicited by monaural 1000 Hz amplitude modulation tones at 80 dB SPL, with the
      amplitude modulated at 39 Hz. The AEFs were elicited by monaural 1000 Hz tone
      bursts of 60 ms duration (rise and fall times of 10 ms, plateau time of 40 ms) at
      80 dB SPL. The results indicated that continuous white noise at 70 dB SPL
      presented to the contralateral ear did not suppress the N100 m response in either
      hemisphere, but significantly reduced the amplitude of the 40-Hz ASSF in both
      hemispheres with asymmetry in that suppression of the 40-Hz ASSF was greater in
      the right hemisphere. Different effects of contralateral white noise on these two
      responses may reflect different functional auditory processes in the cortices.

PMID- 21945468
TI  - Analysis of a simulation algorithm for direct brain drug delivery.
AB  - Convection enhanced delivery (CED) achieves targeted delivery of drugs with a
      pressure-driven infusion through a cannula placed stereotactically in the brain.
      This technique bypasses the blood brain barrier and gives precise distributions
      of drugs, minimizing off-target effects of compounds such as viral vectors for
      gene therapy or toxic chemotherapy agents. The exact distribution is affected by
      the cannula positioning, flow rate and underlying tissue structure. This study
      presents an analysis of a simulation algorithm for predicting the distribution
      using baseline MRI images acquired prior to inserting the cannula. The MRI images
      included diffusion tensor imaging (DTI) to estimate the tissue properties. The
      algorithm was adapted for the devices and protocols identified for upcoming
      trials and validated with direct MRI visualization of gadoinium in 20 infusions
      in non-human primates. We found strong agreement between the size and location of
      the simulated and gadolinium volumes, demonstrating the clinical utility of this
      surgical planning algorithm.

PMID- 21945469
TI  - In vivo quantification of dopamine transporters in mice with unilateral 6-OHDA
      lesions using [11C]methylphenidate and PET.
AB  - Quantification of the binding of [11C]methylphenidate to the dopamine transporter
      (DAT) using positron emission tomography (PET) is often used to evaluate the
      integrity of dopaminergic neurons in the striatal regions of the brain. Over the
      past decade, many genetically engineered mouse models of human disease have been
      developed and have become particularly useful for the study of disease onset and
      progression over time. Quantitative imaging of small structures such as the mouse
      brain is especially challenging. Thus, the aims of this study were (1) to
      evaluate the accuracy of quantifying DAT binding using in vivo PET and (2) to
      examine the impact of different methodologies. METHODS: Eight mice were scanned
      with [11C]methylphenidate under true or transient equilibrium conditions using a
      bolus and constant infusion protocol or a bolus injection protocol to evaluate
      the accuracy of the Logan graphical approach for [11C]methylphenidate imaging in
      mice. Displacement with unlabeled methylphenidate (0.1, 3 and 10 mg/kg) was used
      to verify specific binding. In a second experiment, 30 mice were lesioned by
      injection of 6-hydroxydopamine (6-OHDA) at doses of 0, 2 or 4 MUg (n=10) into the
      right striatum to assess the dose-dependent correlation between the PET signal
      and dopaminergic degeneration. In addition, we performed test-retest experiments
      and used ex vivo autoradiography (AR) to validate the effect of partial volume on
      the accuracy of the [11C]methylphenidate PET quantification in the mouse
      striatum. RESULTS: The binding potentials (BPND) calculated from the Logan
      graphical analysis under transient equilibrium conditions (1.03+/-0.1) were in
      excellent agreement with those calculated at true equilibrium (1.07+/-0.1).
      Displacement of specific binding with 0.1, 3 and 10mg/kg methylphenidate resulted
      in 38%, 77% and 81% transporter occupancy in the striatum. Intra-striatal
      injections of 6-OHDA caused a dose-dependent decrease in the specific binding of
      [11C]methylphenidate to the DAT in the striatum. The BPND was reduced by 49% and
      61% after injection with 2 and 4 MUg of 6-OHDA, respectively. The test-retest
      reproducibility was 6% in the healthy striatum and 27% in the lesioned striatum.
      In addition, only a small (15%) difference was found between the
      [11C]methylphenidate DVR-1 values determined by PET and AR on the healthy side,
      and no differences were observed on the lesioned side. CONCLUSION: The present
      work demonstrates for the first time that [11C]methylphenidate PET is useful for
      the quantification of striatal dopamine transporters at the dopaminergic nerve
      terminals in the mouse striatum; therefore, this marker may be used as a
      biomarker in genetically engineered mouse models of neurodegenerative disorders.
      However, only changes resulting in greater than 10% differences in BPND values
      can reliably be detected in vivo.

PMID- 21945470
TI  - Establishing the reproducibility of two approaches to quantify white matter tract
      integrity in stroke.
AB  - Diffusion tensor imaging can provide unique and detailed information about white
      matter anatomy following stroke. Fiber tract reconstruction using tract-based
      techniques and cross-sectional region of interest delineation are two common
      approaches to quantify white matter integrity. After stroke, white matter tract
      integrity can be affected both locally and distally to the primary lesion
      location. It has been shown that tract disruption is associated with degree of
      functional impairment and response to skill training in participants with stroke.
      However, the reliability and validity of these approaches has not been
      systematically evaluated nor have the two approaches been directly compared in
      individuals with chronic stroke. Ten well-recovered individuals with chronic,
      right-sided, ischemic stroke in the sub-cortex and ten age-, gender- and
      handedness-matched healthy participants were studied. Semi-automated tractography
      of the ipsi- and contralesional corticospinal tract and cross-sectional region of
      interest drawing of the posterior limb of the internal capsule were performed
      bilaterally. Fractional anisotropy (FA) values and the hemispheric asymmetry in
      FA were the primary measures of tract integrity. Two raters performed each
      analysis method twice to evaluate inter- and intra-rater reliability.
      Participants with stroke were compared to healthy individuals to determine
      validity of each analysis approach. Correlational analyses were conducted to
      examine the relationships between the two approaches and the association between
      approaches and upper extremity motor impairment. Both analyses methods generally
      demonstrated good to excellent intra- and inter-rater reliability in each group
      (p<0.05). Stroke participants demonstrated lower mean FA values in both ipsi- and
      contralesional tract integrity, and larger FA hemispheric asymmetry as compared
      with healthy individuals (p<0.05). Comparison between the analysis approaches
      revealed significant associations between approaches across both groups and
      within each group (p<0.05). In stroke, individual tract integrity was not
      correlated between approaches for ipsilesional (r=0.26) or contralesional (0.15)
      tracts, nor was FA hemispheric asymmetry (r=0.18). Additionally, contralesional
      mean FA quantified with the cross-sectional approach correlated with upper
      extremity motor impairment (r=0.69). Importantly, this study is the first to
      systematically characterize the reliability of tract-based and cross-sectional
      DTI analysis approaches in well-recovered individuals with chronic stroke and
      matched healthy participants. Results suggest both tract-based and cross
      sectional approaches to evaluate white matter tract integrity are reliable, can
      differentiate between groups of stroke and healthy participants, and are
      associated with one another. However, only mean FA values for the contralesional
      side derived using the cross-sectional approach were related to upper extremity
      impairment. Our findings suggest that each approach provides complimentary rather
      than redundant information regarding integrity and support the use of both
      approaches in combination in future investigations in well-recovered individuals
      with stroke.

PMID- 21945471
TI  - Characterising the dynamics of EEG waveforms as the path through parameter space
      of a neural mass model: application to epilepsy seizure evolution.
AB  - In this paper we propose that the dynamic evolution of EEG activity during
      epileptic seizures may be characterised as a path through parameter space of a
      neural mass model, reflecting gradual changes in underlying physiological
      mechanisms. Previous theoretical studies have shown how boundaries in parameter
      space of the model (so-called bifurcations) correspond to transitions in EEG
      waveforms between apparently normal, spike and wave and subsequently poly-spike
      and wave activity. In the present manuscript, we develop a multi-objective
      genetic algorithm that can estimate parameters of an underlying model from
      clinical data recordings. A standard approach to this problem is to transform
      both clinical data and model output into the frequency domain and then choose
      parameters that minimise the difference in their respective power spectra.
      Instead in the present manuscript, we estimate parameters in the time domain,
      their choice being determined according to the best fit obtained between the
      model output and specific features of the observed EEG waveform. This results in
      an approximate path through the bifurcation plane of the model obtained from
      clinical data. We present comparisons of such paths through parameter space from
      separate seizures from an individual subject, as well as between different
      subjects. Differences in the path reflect subtleties of variation in the dynamics
      of EEG, which at present appear indistinguishable using standard clinical
      techniques.

PMID- 21945472
TI  - Role of phosphorylation in progesterone receptor signaling and specificity.
AB  - Progesterone receptors (PR), in concert with peptide growth factor-initiated
      signaling pathways, initiate massive expansion of the epithelial cell compartment
      associated with the process of alveologenesis in the developing mammary gland. PR
      dependent signaling events also contribute to inappropriate proliferation
      observed in breast cancer. Notably, PR-B isoform-specific cross talk with growth
      factor-driven pathways is required for the proliferative actions of progesterone.
      Indeed, PRs act as heavily phosphorylated transcription factor "sensors" for
      mitogenic protein kinases that are often elevated and/or constitutively activated
      in invasive breast cancers. In addition, phospho-PR-target genes frequently
      include the components of mitogenic signaling pathways, revealing a mechanism for
      feed-forward signaling that confers increased responsiveness of, PR +mammary
      epithelial cells to these same mitogenic stimuli. Understanding the mechanisms
      and isoform selectivity of PR/kinase interactions may yield further insight into
      targeting altered signaling networks in breast and other hormonally responsive
      cancers (i.e. lung, uterine and ovarian) in the clinic. This review focuses on PR
      phosphorylation by mitogenic protein kinases and mechanisms of PR-target gene
      selection that lead to increased cell proliferation.

PMID- 21945473
TI  - Progesterone regulation of stem and progenitor cells in normal and malignant
      breast.
AB  - Progesterone plays an important, if not controversial, role in mammary epithelial
      cell proliferation and differentiation. Evidence supports that progesterone
      promotes rodent mammary carcinogenesis under some conditions, progesterone
      receptors (PR) are necessary for murine mammary gland tumorigenesis, and
      exogenous progestin use in post-menopausal women increases breast cancer risk.
      Thus, the progesterone/PR signaling axis can promote mammary tumorigenesis,
      albeit in a context-dependent manner. A mechanistic basis for the tumor promoting
      actions of progesterone has thus far remained unknown. Recent studies, however,
      have identified a novel role for progesterone in controlling the number and
      function of stem and progenitor cell populations in the normal human and mouse
      mammary glands, and in human breast cancers. These discoveries promise to reshape
      our perception of progesterone function in the mammary gland, and have spawned
      new hypotheses for how progestins may increase the risk of breast cancer. Here we
      review studies on progesterone regulation of mammary stem cells in normal and
      malignant tissue, and their implications for breast cancer risk, tumorigenesis,
      and tumor behavior.

PMID- 21945474
TI  - Multiple nuclear receptor signaling pathways mediate the actions of synthetic
      progestins in target cells.
AB  - Synthetic progestins are used clinically to treat a variety of women's health
      issues. Although progestins are designed to signal through the progesterone
      receptor (PR) to elicit specific pharmacological effects, they can also variably
      bind to and influence the activity of other nuclear receptors within target
      tissues, particularly the androgen and glucocorticoid receptors and, in some
      cases, they regulate mineralocorticoid and estrogen receptors. This article
      reviews current knowledge on progestin cross-talk to nuclear receptors other than
      PR, their resultant effect on receptor function in different in vitro models and
      the potential consequences of this activity for breast, ovarian and endometrial
      cancer. The impact of cell and tissue context, assay type, steroid metabolism and
      hormonal milieu in determining progestin-mediated activity are also presented.
      Collectively this review highlights the complexity of progestin action and the
      need for consideration of multiple mechanisms that act in concert to influence
      their ultimate biological activity.

PMID- 21945475
TI  - Interplay between progesterone and prolactin in mammary development and
      implications for breast cancer.
AB  - Progesterone and prolactin remodel mammary morphology during pregnancy by acting
      on the mammary epithelial cell hierarchy. The roles of each hormone in mammary
      development have been well studied, but evidence of signalling cross-talk between
      progesterone and prolactin is still emerging. Factors such as receptor activator
      of NFkB ligand (RANKL) may integrate signals from both hormones to orchestrate
      their joint actions on the epithelial cell hierarchy. Common targets of
      progesterone and prolactin signalling are also likely to integrate their pro
      proliferative actions in breast cancer. Therefore, a thorough understanding of
      the interplay between progesterone and prolactin in mammary development may
      reveal therapeutic targets for breast cancer. This review summarises our
      understanding of Pg and PRL action in mammary gland development before focusing
      on molecular mechanisms of signalling cross-talk and the implications for breast
      cancer.

PMID- 21945476
TI  - Nuclear receptor HR4 plays an essential role in the ecdysteroid-triggered gene
      cascade in the development of the hemimetabolous insect Blattella germanica.
AB  - Despite the differences in the developmental strategies between hemimetabolous
      and holometabolous insects, a common feature between both types of development is
      that periodic pulses of the steroid hormone 20-hydroxyecdysone (20E) dictate each
      developmental transition. Although the molecular action of 20E has been
      extensively studied in holometabolous insects, data on hemimetabolous is scarce.
      To address this, we have used the German cockroach Blattella germanica to show
      that 20E signals through a transcriptional cascade of the nuclear hormone
      receptor-encoding genes BgE75, BgHR3 and BgFTZ-F1. Here, we report the isolation
      and functional characterization of BgHR4, another nuclear receptor involved in
      this cascade. Expression studies along with tissue incubations and RNAi
      experiments show that cross-regulation between BgE75 and BgHR3 directs the
      expression of BgHR4. Finally, we have also shown that BgHR4 is an essential gene
      required for successfully completing nymphal-nymphal and nymphal-adult
      transitions, by allowing the appropriate delay in the induction of BgFTZ-F1.

PMID- 21945477
TI  - Paracrine signaling by progesterone.
AB  - Steroid hormones coordinate and control the development and function of many
      organs and are implicated in many pathological processes. Progesterone signaling,
      in particular, is essential for several important female reproductive functions.
      Physiological effects of progesterone are mediated by its cognate receptor,
      expressed in a subset of cells in target tissues. Experimental evidence has
      accumulated that progesterone acts through both cell intrinsic as well as
      paracrine signaling mechanisms. By relegating the hormonal stimulus to paracrine
      signaling cascades the systemic signal gets amplified locally and signaling
      reaches different cell types that are devoid of hormone receptors. Interestingly,
      distinct biological responses to progesterone in different target tissues rely on
      several tissue-specific and some common paracrine factors that coordinate
      biological responses in different cell types. Evidence is forthcoming that the
      intercellular signaling pathways that control development and physiological
      functions are important in tumorigenesis.

PMID- 21945478
TI  - Intra-hemispheric functional coupling of alpha rhythms is related to golfer's
      performance: a coherence EEG study.
AB  - It has been shown that frontocentral electroencephalographic (EEG) alpha rhythms
      (about 10-12 Hz) were higher in amplitude in expert golfers in successful than
      unsuccessful putts, possibly reflecting the idea that amplitude regulation of
      frontocentral alpha rhythms is a physiological mechanism implied in motor control
      and golfer's performance (Babiloni et al., 2008). Here, we tested the ancillary
      hypothesis that golfer's performance is also associated to an improved
      coordination of cortical activity, as reflected by functional coupling of alpha
      rhythms across cortical regions. To this aim, between-electrodes spectral
      coherence was computed from spatially enhanced EEG data of the mentioned study
      (i.e. right handed 12 expert golfers; augmented 10-20 system; surface Laplacian
      estimation). Low- (about 8-10 Hz) and high-frequency (about 10-12 Hz) alpha sub
      bands were considered with reference to individual alpha frequency peak.
      Statistical results showed that intra-hemispheric low-frequency alpha coherence
      in bilateral parietal-frontal (P3-F3 and P4-F4 electrodes) and parietal-central
      (P3-C3 and P4-C4 electrodes) was higher in amplitude in successful than
      unsuccessful putts (p<0.004). The same was true for intra-hemispheric high
      frequency alpha coherence in bilateral parietal-frontal regions (p<0.004). These
      findings suggest that intra-hemispheric functional coupling of cortical alpha
      rhythms between "visuo-spatial" parietal area and other cortical areas is
      implicated in fine motor control of golfer's performance.

PMID- 21945479
TI  - Reactivity of alpha rhythms to eyes opening is lower in athletes than non
      athletes: a high-resolution EEG study.
AB  - In the present study, we tested the hypothesis that compared with non-athletes,
      elite athletes are characterized by a reduction of reactivity of
      electroencephalographic (EEG) alpha rhythms (about 8-12 Hz) to eyes opening in
      the condition of resting state, as a possible index of spatially selective
      cortical activation (i.e. "neural efficiency"). EEG data (56 channels; Eb
      Neuro(c)) were recorded in 18 elite karate athletes and 28 non-athletes during
      resting state eyes-closed and eyes-open conditions. The EEG data were spatially
      enhanced by surface Laplacian estimation. Cortical activity was indexed by task
      related power decrease (TRPD), namely the alpha power during the eyes-open
      referenced to the eyes-closed resting condition. Low-frequency alpha TRPD (about
      8-10 Hz) was lower in the elite karate athletes than in the non-athletes in
      frontal (p<0.00002), central (p<0.008) and right occipital (p<0.02) areas.
      Similarly, high-frequency alpha TRPD (about 10-12 Hz) was lower in the elite
      karate athletes than in the non-athletes in frontal (p<0.00009) and central
      (p<0.01) areas. These results suggest that athletes' brain is characterized by
      reduced cortical reactivity to eyes opening in the condition of resting state, in
      line with the "neural efficiency" hypothesis. The present study motivates future
      research evaluating the extent to which this general functional brain feature is
      related to heritable trait or intensive visuo-motor training of elite athletes.

PMID- 21945480
TI  - Music perception and imagery in EEG: alpha band effects of task and stimulus.
AB  - Previous work has shown that mental imagination of sound generally elicits an
      increase of alpha band activity (8-12 Hz) in the electroencephalogram (EEG). In
      addition, alpha activity has been shown to be related to aspects of music
      processing. In the current study, EEG signatures were investigated for perception
      and imagery of two different natural musical phrases. The responses are compared
      between tasks and between stimuli. For all tasks and stimuli, posterior alpha
      band activity was seen, but differences are shown in the power of this response.
      As expected, imagery resulted in a significantly stronger alpha activation than
      perception. The comparison of the averaged responses to the stimuli also showed a
      difference in alpha power, although this effect is seen in different directions.
      These results are interpreted to indicate that both the tasks and the stimuli
      modulate an attentional network, which may relate to the inhibition of non-task
      relevant cortical areas, as well as engagement with the music.

PMID- 21945481
TI  - Motor cortex excitability in vascular depression.
AB  - The aim of this study was to evaluate excitatory/inhibitory intracortical circuit
      changes in patients with vascular depression, and whether there are any
      interhemispheric differences of motor cortical excitability. Fifteen vascular
      depressed elderly (VD), ten nondepressed subcortical vascular disease patients
      (SVD) and ten age-matched controls underwent bilateral motor threshold and paired
      pulse studies. They were also assessed for their brain vascular burden at MRI and
      neuropsychological profile. Executive dysfunction and apathy were significantly
      higher in VD; we were unable to find significant differences in resting motor
      threshold, cortical silent period and paired-pulse curves between VD, SVD and
      controls, and between the two hemispheres in the VD group. Our findings might
      suggest that neurophysiological mechanisms underlying VD differ from those
      previously reported in Major Depression (reduced excitability in the left
      hemisphere) and seem to be similar to those of patients with SVD. Our findings
      also, support the "vascular depression" hypothesis, suggesting that in VD
      patients the depressive syndrome is not the primary disease but can be considered
      as one of the clinical manifestations in the wide symptom spectrum of the
      cerebral small vessel disease.

PMID- 21945482
TI  - Effects of ocular transverse chromatic aberration on peripheral word
      identification.
AB  - Transverse chromatic aberration (TCA) smears the retinal image of peripheral
      stimuli. We previously found that TCA significantly reduces the ability to
      recognize letters presented in the near fovea by degrading image quality and
      exacerbating crowding effect from adjacent letters. The present study examined
      whether TCA has a significant effect on near foveal and peripheral word
      identification, and whether within-word orthographic facilitation interacts with
      TCA effect to affect word identification. Subjects were briefly presented a 6- to
      7-letter word of high or low frequency in each trial. Target words were generated
      with weak or strong horizontal color fringe to attenuate the TCA in the right
      periphery and exacerbate it in the left. The center of the target word was 1
      degrees , 2 degrees , 4 degrees , and 6 degrees  to the left or right of a
      fixation point. Subject's eye position was monitored with an eye-tracker to
      ensure proper fixation before target presentation. They were required to report
      the identity of the target word as soon and accurately as possible. Results show
      significant effect of color fringe on the latency and accuracy of word
      recognition, indicating existing TCA effect. Observed TCA effect was more salient
      in the right periphery, and was affected by word frequency more there.
      Individuals' subjective preference of color-fringed text was correlated to the
      TCA effect in the near periphery. Our results suggest that TCA significantly
      affects peripheral word identification, especially when it is located in the
      right periphery. Contextual facilitation such as word frequency interacts with
      TCA to influence the accuracy and latency of word recognition.

PMID- 21945483
TI  - Targeting of mouse guanylate cyclase 1 (Gucy2e) to Xenopus laevis rod outer
      segments.
AB  - Photoreceptor guanylate cyclase (GC1) is a transmembrane protein and responsible
      for synthesis of cGMP, the secondary messenger of phototransduction. It consists
      of an extracellular domain, a single transmembrane domain, and an intracellular
      domain. It is unknown how GC1 targets to the outer segments where it resides. To
      identify a putative GC1 targeting signal, we generated a series of peripheral
      membrane and transmembrane constructs encoding extracellular and intracellular
      mouse GC1 fragments fused to EGFP. The constructs were expressed in Xenopus
      laevis rod photoreceptors under the control of the rhodopsin promoter. We
      examined the localization of GFP-GC1 fusion proteins containing the complete GC1
      sequence, or partial GC1 sequences, which were membrane-associated via either the
      GC1 transmembrane domain or the rhodopsin C-terminal palmitoyl chains. Full
      length GFP-GC1 targeted to the rod outer segment disk rims. As a group, fusion
      proteins containing the entire cytoplasmic domain of GC1 targeted to the OS,
      whereas other fusion proteins containing portions of the cytoplasmic or the
      extracellular domains did not. We conclude that GC1 likely has no single linear
      peptide-based OS targeting signal. Our results suggest targeting is due to either
      multiple weak signals in the cytoplasmic domain of GC1, or co-transport to the OS
      with an accessory protein.

PMID- 21945484
TI  - Imaging the high-affinity state of the dopamine D2 receptor in vivo: fact or
      fiction?
AB  - Positron Emission Tomography (PET) has been used for more than three decades to
      image and quantify dopamine D2 receptors (D2R) in vivo with antagonist
      radioligands but in the recent years agonist radioligands have also been
      employed. In vitro competition studies have demonstrated that agonists bind to
      both a high and a low-affinity state of the D2Rs, of which the high affinity
      state reflects receptors that are coupled to G-proteins and the low-affinity
      state reflects receptors uncoupled from G-proteins. In contrast, antagonists bind
      with uniform affinity to the total pool of receptors. Results of these studies
      led to the proposal that D2Rs exist in high and low-affinity states for agonists
      in vivo and sparked the development and use of agonist radioligands for PET
      imaging with the primary purpose of measuring the proportion of receptors in the
      high-affinity (activating) state. Although several lines of research support the
      presence of high and low-affinity states of D2Rs and their detection by in vivo
      imaging paradigms, a growing body of controversial data has now called this into
      question. These include both in vivo and ex vivo studies of anesthesia effects,
      rodent models with increased proportions of high-affinity state D2Rs as well as
      the molecular evidence for stable receptor-G-protein complexes. In this
      commentary we review these data and discuss the evidence for the in vivo
      existence of D2Rs configured in high and low-affinity states and whether or not
      the high-affinity state of the D2R can, in fact, be imaged in vivo with agonist
      radioligands.

PMID- 21945486
TI  - Comparison of local and systemic alendronate on distraction osteogenesis.
AB  - This study compared the effect of systemic and local administration of
      alendronate on distraction osteogenesis in rabbit mandibles. Thirty New Zealand
      white rabbits were allocated to 3 groups: 10 rabbits for systemic alendronate; 9
      for local alendronate; and 11 as controls. After a 5 day latency period,
      distraction was performed at a rate of 0.8mm/day for 9 days via a custom-made
      distractor. Animals were killed at the end of the consolidation period of 28
      days. The distracted mandibles were harvested and evaluated by plain radiography,
      computed tomography (CT), dual energy X-ray absorptiometry (DEXA), and
      histomorphometry. Histologically, comparing the systemic and local alendronate
      groups, there were no statistically significant differences in the bone healing
      parameters, but each group showed a statistically superior effect over the
      control group (p<0.05). Quantitative CT evaluation showed a significant
      difference mean in the density of the regeneration between experimental and
      control groups. There was a significant increase in mean bone mineral density in
      the experimental groups compared with the control group. Histologic, CT, and DEXA
      analysis demonstrated that using systemic and local alendronate may be effective
      in accelerating new bone formation in the distraction gap in rabbit mandibles.

PMID- 21945485
TI  - Molecular and functional heterogeneity of T regulatory cells.
AB  - Naturally occurring CD4+ T regulatory (Treg) cells are produced during maturation
      in the thymus and have a mandatory role in maintaining homeostasis and immune
      quiescence. Development and function of Treg cells depends on the transcription
      factor forkhead box P3 (Foxp3), which is necessary and sufficient for Treg cell
      function. Currently emerging evidence indicates Treg cells display molecular and
      functional heterogeneity and can be categorized into naive and effector- or
      memory-like cells, which can produce effector cytokines supporting the idea that
      Treg cells retain plasticity. The role of Treg cells that acquire these
      properties remains unclear and is currently under intense investigation. In this
      review, we summarize recent advances on the differentiation of effector- or
      memory-like Treg cells, the impact of the cytokine milieu on the molecular and
      functional heterogeneity of Treg cells, and the clinical implications of the
      heterogeneity and specialization of Treg cells.

PMID- 21945487
TI  - On the leveling-off properties of the new bioequivalence limits for highly
      variable drugs of the EMA guideline.
AB  - Recently, the European Medicines Agency (EMA) issued a new guideline on the
      investigation of bioequivalence (BE). In case of highly variable drugs, this
      guideline proposes that the acceptance limits for C(max) can gradually be
      expanded as a function of within-subject variability (CV(wR)). Actually, these BE
      limits exhibit leveling-off properties since they are not allowed to scale
      continuously, but only up to CV(wR)=50%. To avoid the risk of accepting two drug
      products which may differ significantly, this EMA guideline also proposes the use
      of a secondary constraint criterion on the geometric mean ratio (GMR) of the two
      products under comparison. Aim of this study was to explore the leveling-off
      properties of the new EMA limits in comparison to other approaches, as well as to
      assess the impact of the complementary GMR criterion on the ability to declare
      bioequivalence. Simulated bioequivalence studies and extreme GMR plots were used
      to assess the performance of the EMA limits. Three sequence, three period (3*3)
      crossover studies with two treatments (T and R) were simulated. The R product was
      considered to be administered twice, while the T only once (i.e., TRR/RTR/RRT).
      Among others, this study revealed the leveling-off properties of the new EMA
      limits. It was also shown that the complementary GMR-constraint is only effective
      when a large sample size is used and at regions of CV(wR) close to 50%. This GMR
      criterion begins to be effective at sample sizes around 60 and becomes more
      prominent as the number of subjects participating in the BE study increases. For
      CV(wR) values lower than 50%, the GMR-constraint has no role. In case of within
      subject variabilities greater than 50%, the impact of the GMR-constraint
      diminishes due to the leveling-off properties of the EMA limits. Compared to the
      classic 0.80-1.25 or the extended 0.75-1.33 criteria, the new EMA limits are more
      liberal at high CV(wR) values and allow greater differences between the two drug
      products to be declared bioequivalent. Finally, this study showed that the use of
      an approximate value (0.760) on the scaling factor proposed by EMA, has no impact
      on the performance of the new BE limits compared to other more accurate
      approaches.

PMID- 21945488
TI  - Interaction of fluvastatin with the liver-specific Na+ -dependent taurocholate
      cotransporting polypeptide (NTCP).
AB  - It has been reported that polymorphisms in the organic anion transporting
      polypeptide 1B1 (OATP1B1, SLCO1B1) result in decreased hepatic uptake of
      simvastatin carboxy acid, the active metabolite of simvastatin. This is not the
      case for fluvastatin and it has been hypothesized that for this drug other
      hepatic uptake pathways exist. Here, we studied whether Na(+)-dependent
      taurocholate co-transporting polypeptide (NTCP, SLC10A1) can be an alternative
      hepatic uptake route for fluvastatin. Chinese Hamster Ovary cells transfected
      with human NTCP (CHO-NTCP) were used to investigate the inhibitory effect of
      fluvastatin and other statins on [(3)H]-taurocholic acid uptake ([(3)H]-TCA).
      Statin uptake by CHO-NTCP and cryopreserved human hepatocytes was assessed via LC
      MS/MS. Fluvastatin appeared to be a potent and competitive inhibitor of [(3)H]
      TCA uptake (IC(50) of 40MUM), pointing to an interaction at the level of the bile
      acid binding pocket of NTCP. The inhibitory action of other statins was also
      studied, which revealed that statin inhibitory potency increased with molecular
      descriptors of lipophilicity: calculated logP (r(2)=0.82, p=0.034), logD(7.4)
      (r(2)=0.77, p=0.0001). Studies in CHO-NTCP cells showed that fluvastatin was
      indeed an NTCP substrate (K(m) 250+/-30MUM, V(max) 1340+/-50ng/mg total cell
      protein/min). However, subsequent studies revealed that at clinically relevant
      plasma concentrations, NTCP contributed minimally to overall accumulation in
      human hepatocytes. In conclusion, fluvastatin interacts with NTCP at the level of
      the bile acid binding pocket and is an NTCP substrate. However, under normal
      conditions, NTCP-mediated uptake of this drug seems not to be a significant
      hepatocellular uptake pathway.

PMID- 21945489
TI  - Why is particulate matter produced by wildfires toxic to lung macrophages?
AB  - The mechanistic basis of the high toxicity to lung macrophages of coarse PM from
      the California wildfires of 2008 was examined in cell culture experiments with
      mouse macrophages. Wildfire PM directly killed macrophages very rapidly in cell
      culture at relatively low doses. The wildfire coarse PM is about four times more
      toxic to macrophages on an equal weight basis than the same sized PM collected
      from normal ambient air (no wildfires) from the same region and season. There was
      a good correlation between the extent of cytotoxicity and the amount of oxidative
      stress observed at a given dose of wildfire PM in vitro. Our data implicate NF
      kappaB signaling in the response of macrophages to wildfire PM, and suggest that
      most, if not all, of the cytotoxicity of wildfire PM to lung macrophages is the
      result of oxidative stress. The relative ratio of toxicity and of expression of
      biomarkers of oxidant stress between wildfire PM and "normal" PM collected from
      ambient air is consistent with our previous results in mice in vivo, also
      suggesting that most, if not all, of the cytotoxicity of wildfire PM to lung
      macrophages is the result of oxidative stress. Our findings from this and earlier
      studies suggest that the active components of coarse PM from the wildfire are
      heat-labile organic compounds. While we cannot rule out a minor role for
      endotoxin in coarse PM preparations from the collected wildfire PM in our
      observed results both in vitro and in vivo, based on experiments using the
      inhibitor Polymyxin B most of the oxidant stress and pro-inflammatory activity
      observed was not due to endotoxin.

PMID- 21945490
TI  - Actions of juglone on energy metabolism in the rat liver.
AB  - Juglone is a phenolic compound used in popular medicine as a phytotherapic to
      treat inflammatory and infectious diseases. However, it also acts as an uncoupler
      of oxidative phosphorylation in isolated liver mitochondria and, thus, may
      interfere with the hepatic energy metabolism. The purpose of this work was to
      evaluate the effect of juglone on several metabolic parameters in the isolated
      perfused rat liver. Juglone, in the concentration range of 5 to 50MUM, stimulated
      glycogenolysis, glycolysis and oxygen uptake. Gluconeogenesis from both lactate
      and alanine was inhibited with half-maximal effects at the concentrations of 14.9
      and 15.7MUM, respectively. The overall alanine transformation was increased by
      juglone, as indicated by the stimulated release of ammonia, urea, l-glutamate,
      lactate and pyruvate. A great increase (9-fold) in the tissue content of alpha
      ketoglutarate was found, without a similar change in the l-glutamate content. The
      tissue contents of ATP were decreased, but those of ADP and AMP were increased.
      Experiments with isolated mitochondria fully confirmed previous notions about the
      uncoupling action of juglone. It can be concluded that juglone is active on
      metabolism at relatively low concentrations. In this particular it resembles more
      closely the classical uncoupler 2,4-dinitrophenol. Ingestion of high doses of
      juglone, thus, presents the same risks as the ingestion of 2,4-dinitrophenol
      which comprise excessive compromising of ATP production, hyperthermia and even
      death. Low doses, i.e., moderate consumption of natural products containing
      juglone, however, could be beneficial to health if one considers recent reports
      about the consequences of chronic mild uncoupling.

PMID- 21945491
TI  - Contribution of aquaporin 9 and multidrug resistance-associated protein 2 to
      differential sensitivity to arsenite between primary cultured chorion and amnion
      cells prepared from human fetal membranes.
AB  - Arsenic trioxide (arsenite, As(III)) has shown a remarkable clinical efficacy,
      whereas its side effects are still a serious concern. Therefore, it is critical
      to understand the effects of As(III) on human-derived normal cells for revealing
      the mechanisms underlying these side effects. We examined the effects of As(III)
      on primary cultured chorion (C) and amnion (A) cells prepared from human fetal
      membranes. A significant dose-dependent As(III)-mediated cytotoxicity was
      observed in the C-cells accompanied with an increase of lactate dehydrogenase
      (LDH) release. Higher concentrations of As(III) were required for the A-cells to
      show cytotoxicity and LDH release, suggesting that the C-cells were more
      sensitive to As(III) than the A-cells. The expression levels of aquaporin 9
      (AQP9) were approximately 2 times higher in the C-cells than those in the A
      cells. Both intracellular arsenic accumulation and its cytotoxicity in the C
      cells were significantly abrogated by sorbitol, a competitive AQP9 inhibitor, in
      a dose-dependent manner. The protein expression levels of multidrug resistance
      associated protein (MRP) 2 were downregulated by As(III) in the C-cells, but not
      in the A-cells. No significant differences in the expression levels of MRP1 were
      observed between C- and A-cells. The protein expression of P-glycoprotein (P-gp)
      was hardly detected in both cells, although a detectable amount of its mRNA was
      observed. Cyclosporine A, a broad-spectrum inhibitor for ABC transporters, and
      MK571, a MRP inhibitor, but not PGP-4008, a P-gp specific inhibitor, potently
      sensitized both cells to As(III)-mediated cytotoxicity. These results suggest
      that AQP9 and MRP2 are involved in controlling arsenic accumulation in these
      normal cells, which then contribute to differential sensitivity to As(III)
      cytotoxicity between these cells.

PMID- 21945492
TI  - Suppression of dendritic cells' maturation and functions by daidzein, a
      phytoestrogen.
AB  - Isoflavones are ubiquitous compounds in foods and in the environment in general.
      Daidzein and genistein, the best known of isoflavones, are structurally similar
      to 17beta-estradiol and known to exert estrogenic effects. They also evidence a
      broad variety of biological properties, including antioxidant, anti-carcinogenic,
      anti-atherogenic and anti-osteoporotic activities. Previously, daidzein was
      reported to increase the phagocytic activity of peritoneal macrophages and
      splenocyte proliferation, and to inhibit nitric oxide (NO) production in
      macrophages. However, its potential impacts on immune response in dendritic cells
      (DCs), antigen-presenting cells that link innate and adaptive immunity, have yet
      to be clearly elucidated. In this study, we evaluated the effects of isoflavones
      on the maturation and activation of DCs. Isoflavones (formononetin, daidzein,
      equol, biochanin A, genistein) were found to differentially affect the expression
      of CD86, a costimulatory molecule, on lipopolysaccharide (LPS)-stimulated DCs. In
      particular, daidzein significantly and dose-dependently inhibited the expression
      levels of maturation-associated cell surface markers including CD40,
      costimulatory molecules (CD80, CD86), and major histocompatibility complex class
      II (I-A(b)) molecule on LPS-stimulated DCs. Daidzein also suppressed pro
      inflammatory cytokine production such as IL-12p40, IL-6 and TNF-alpha, whereas it
      didn't affect IL-10 and IL-1beta expression. Furthermore, daidzein enhanced
      endocytosis and inhibited the allo-stimulatory ability of LPS-stimulated DCs on T
      cells, indicating that daidzein treatment can inhibit the functional maturation
      of DCs. These results demonstrate that daidzein may exhibit immunosuppressive
      activity by inhibiting the maturation and activation of DCs.

PMID- 21945494
TI  - Exploiting mucosal surfaces for the development of mucosal vaccines.
AB  - Mucosal immunity covers a variety of mucosal surfaces susceptible to different
      pathogens. This review highlights the diversity of mucosal tissues and the unique
      microenvironments in which an immune response is generated. It argues that tissue
      specific factors present throughout mucosal tissues and lymph nodes determine the
      differentiation into IgA-producing B cells, which in turn determines their
      migration patterns. Mucosal immunity can therefore be induced when antigen is
      delivered at any mucosal tissue without the need for specific 'mucosal adjuvants'
      or targeting to specialised lymphoid structures. Non-oral vaccination strategies
      directed at alternative and more accessible mucosal tissue sites, may provide new
      avenues for both mucosal and systemic immunization, and will be greatly
      facilitated by the use of large animal models.

PMID- 21945493
TI  - Increased CCL24/eotaxin-2 with postnatal ozone exposure in allergen-sensitized
      infant monkeys is not associated with recruitment of eosinophils to airway
      mucosa.
AB  - Epidemiology supports a causal link between air pollutant exposure and childhood
      asthma, but the mechanisms are unknown. We have previously reported that ozone
      exposure can alter the anatomic distribution of CD25+ lymphocytes in airways of
      allergen-sensitized infant rhesus monkeys. Here, we hypothesized that ozone may
      also affect eosinophil trafficking to allergen-sensitized infant airways. To test
      this hypothesis, we measured blood, lavage, and airway mucosa eosinophils in 3
      month old monkeys following cyclical ozone and house dust mite (HDM) aerosol
      exposures. We also determined if eotaxin family members (CCL11, CCL24, CCL26) are
      associated with eosinophil location in response to exposures. In lavage,
      eosinophil numbers increased in animals exposed to ozone and/or HDM. Ozone+HDM
      animals showed significantly increased CCL24 and CCL26 protein in lavage, but the
      concentration of CCL11, CCL24, and CCL26 was independent of eosinophil number for
      all exposure groups. In airway mucosa, eosinophils increased with exposure to HDM
      alone; comparatively, ozone and ozone+HDM resulted in reduced eosinophils. CCL26
      mRNA and immunofluorescence staining increased in airway mucosa of HDM alone
      animals and correlated with eosinophil volume. In ozone+HDM animal groups, CCL24
      mRNA and immunofluorescence increased along with CCR3 mRNA, but did not correlate
      with airway mucosa eosinophils. Cumulatively, our data indicate that ozone
      exposure results in a profile of airway eosinophil migration that is distinct
      from HDM mediated pathways. CCL24 was found to be induced only by combined ozone
      and HDM exposure, however expression was not associated with the presence of
      eosinophils within the airway mucosa.

PMID- 21945495
TI  - Increases in vaccination coverage of healthcare personnel following institutional
      requirements for influenza vaccination: a national survey of U.S. hospitals.
AB  - BACKGROUND: Institutional requirements for influenza vaccination, ranging from
      policies that mandate declinations to those terminating unvaccinated healthcare
      personnel (HCP), are increasingly common in the U.S. Our objective was to
      determine HCP vaccine uptake following requirements for influenza vaccination at
      U.S. hospitals. METHODS: Survey mailed in 2011 to a nationally representative
      sample of 998 acute care hospitals. An institutional requirement was defined as
      an institutional policy that requires receipt or declination of influenza
      vaccination, with or without consequences for vaccine refusal. Respondents
      reported institutional-level, seasonal influenza vaccination coverage, if known,
      during two consecutive influenza seasons: the season prior to (i.e., pre
      requirement), and the first season of requirement (i.e., post-requirement).
      Weighted univariate and multivariate analyses accounted for sampling design and
      non-response. RESULTS: 808 (81.0%) hospitals responded. Of hospitals with
      institutional requirements for influenza vaccination (n=440), 228 hospitals met
      analytic inclusion criteria. Overall, mean reported institutional-level influenza
      vaccination coverage among HCP rose from 62.0% in the pre-requirement season to
      76.6% in the post-requirement season, representing a single-season increase of
      14.7 (95% CI: 12.6-16.7) percentage points. After adjusting for potential
      confounders, single-season increases in influenza vaccination uptake remained
      greater among hospitals that imposed consequences for vaccine refusal, and among
      hospitals with lower pre-requirement vaccination coverage. Institutional
      characteristics were not associated with vaccination increases of differential
      magnitude. CONCLUSION: Hospitals that are unable to improve suboptimal influenza
      vaccination coverage through multi-faceted, voluntary vaccination campaigns may
      consider institutional requirements for influenza vaccination. Rapid and
      measurable increases in vaccination coverage followed institutional requirements
      at hospitals of varying demographic characteristics.

PMID- 21945496
TI  - Look beyond one's own nose: combination of information from publicly available
      sources reveals an association of GATA4 polymorphisms with plasma triglycerides.
AB  - OBJECTIVE: GATA4iKO mice exhibit impeded triglyceride absorption from intestine
      and decreased plasma triglyceride levels. Data in humans are lacking. We
      hypothesized that triglyceride levels might also be regulated by polymorphisms in
      the GATA4 gene in humans. We used publicly available data from different sources
      to evaluate this hypothesis. Our approach is a more often applicable advance to
      uncover associations and their functional implications which would have been
      otherwise missed by standard genome-wide association studies (GWAS). METHODS: We
      used the publicly available GWAS results from 137 SNPs in the GATA4 region for
      triglyceride levels. We embedded these results into the comprehensive functional
      genomics data provided in the UCSC Genome Browser including among others
      information on regulatory elements and interspecies conservation. A concise
      graphical presentation is proposed together with an R function for automatic data
      preparation. This process is presented in an educational manner using a
      screencast to become most useful for other researchers. RESULTS: We observed
      several polymorphisms in and around the GATA4 gene which have a significant
      influence on plasma triglyceride levels with the lowest p-value at SNP rs1466785
      (Bonferroni-corrected p-value = 1.76e-5). The bioinformatic evaluation of this
      locus in publicly available functional genomics data provided converging evidence
      for the presence of a transcriptional regulator downstream of GATA4. CONCLUSION:
      The combination of different sources of data has revealed an association of GATA4
      with triglyceride levels in humans. Our evaluation exemplifies how an integrative
      analysis including both statistical and biological perspectives can shed new
      light on available association data and reveals novel candidate genes, which are
      otherwise hidden in the noisy region below genome-wide significance.

PMID- 21945497
TI  - Effect of local and remote ischemic preconditioning on endothelial function in
      young people and healthy or hypertensive elderly people.
AB  - To verify whether age affects remote preconditioning, we compared healthy young
      people (mean age = 28.0 years, SD: 7.2), healthy elderly people (age = 69.2
      years, SD: 5.0), and hypertensive elderly people (group 3, age = 72.8 years, SD:
      3.9). Each group included 10 participants. The flow-mediated-dilation (FMD) was
      measured after local (same arm) and remote (leg) ischemic preconditioning.
      Healthy elderly people had the greatest increase of FMD after ischemic
      preconditioning compared to baseline (173% after local and 181% after remote
      preconditioning) and young participants the smallest increase (77% after local
      and 69% after remote preconditioning) while hypertensive elderly had an
      intermediate increase (P for comparison across groups: 0.347 for local and 0.064
      for remote preconditioning). However, absolute values of FMD after
      preconditioning were much lower in elderly hypertensive than in healthy young
      adults. Remote preconditioning increases endothelial reactivity in healthy and
      hypertensive elderly. The potential clinical relevance of this finding deserves
      consideration.

PMID- 21945498
TI  - Association of heme oxygenase-1 GT-repeat polymorphism with blood pressure
      phenotypes and its relevance to future cardiovascular mortality risk: an
      observation based on arsenic-exposed individuals.
AB  - OBJECTIVE: Heme oxygenase (HO)-1 is up-regulated as a cellular defense responding
      to stressful stimuli in experimental studies. A GT-repeat length polymorphism in
      the HO-1 gene promoter was inversely correlated to HO-1 induction. Here, we
      reported the association of GT-repeat polymorphism with blood pressure (BP)
      phenotypes, and their interaction on cardiovascular (CV) mortality risk in
      arsenic-exposed cohorts. METHODS: Associations of GT-repeat polymorphism with BP
      phenotypes were investigated at baseline in a cross-sectional design. Effect of
      GT-repeat polymorphism on CV mortality was investigated in a longitudinal design
      stratified by hypertension. GT-repeat variants were grouped by S (<27 repeats) or
      L (>= 27 repeats) alleles. Multivariate analyses were used to estimate the effect
      size after accounting for CV covariates. RESULTS: Totally, 894 participants were
      recruited and analyzed. At baseline, carriers with HO-1 S alleles had lower
      diastolic BP (L/S genotypes, P = 0.014) and a lower possibility of being
      hypertensive (L/S genotypes, P = 0.048). After follow-up, HO-1 S allele was
      significantly associated with a reduced CV risk in hypertensive participants
      [relative mortality ratio (RMR) 0.27 (CI 0.11, 0.69), P = 0.007] but not in
      normotensive. Hypertensive participants without carrying the S allele had a 5.23
      fold increased risk [RMR 5.23 (CI 1.99, 13.69), P = 0.0008] of CV mortality
      compared with normotensive carrying the S alleles. CONCLUSIONS: HO-1 short GT
      repeat polymorphism may play a protective role in BP regulation and CV mortality
      risk in hypertensive individuals against environmental stressors.

PMID- 21945500
TI  - Acute and chronic effects of marathon running on the retinal microcirculation.
AB  - OBJECTIVE: Previous studies indicate an association between marathon running and
      premature atherosclerosis. Retinal vessel diameter alterations, in particular
      narrower arterioles and wider venules, reflect early stages of atherosclerosis,
      but the influence of marathon on the retinal microcirculation is unknown.
      METHODS: Retinal vessel diameters were measured in 85 male runners (age 31-60
      years; previous marathons 0-56) and in 45 age-matched healthy controls using a
      static vessel analyzer. In runners, diameters were also measured immediately and
      24h after a marathon. Cardiovascular risk profiles, clinical chemistry and, in a
      subgroup of 46 runners, peripheral arterial wave reflections were also assessed.
      RESULTS: Runners had larger arterioles (median 196 MUm (IQR 25) vs. 190(25); p =
      0.068) and smaller venules (222(25) vs. 224(18); p = 0.063) than controls,
      resulting in a significantly increased arteriolar-to-venular ratio (AVR;
      0.89(0.08) vs. 0.85(0.07); p < 0.001). In runners, retinal vessel diameters were
      not associated with body mass index, blood pressure, smoking, lipids or training
      history, and no differences were observed between the lowest (0.71-0.84) and
      highest (0.95-1.06) AVR quintiles. The marathon run induced a significant
      increase of AVR (0.91 (0.09); p = 0.007) due to larger arteriolar than venular
      dilatations, correlating weakly to race duration (r = 0.32; p = 0.003) and to a
      lower increase in leucocytes (r = -0.35; p = 0.001). Vessel diameters normalized
      24h after the race. Augmentation index and pulse pressure decreased significantly
      after the race, but no associations with retinal vessel diameters were observed.
      CONCLUSION: Marathon running is not associated with an impairment of the retinal
      microcirculation. These findings contrast previous reports on atherosclerotic
      alterations of peripheral vessels.

PMID- 21945499
TI  - The role of microRNA-145 in human embryonic stem cell differentiation into
      vascular cells.
AB  - BACKGROUND: Recent studies have reported that microRNA-145 (miR-145) is a
      critical mediator in the regulation of proliferation, differentiation, and
      phenotype expression of smooth muscle cells (SMCs). Previously, we established a
      system for differentiating human ESCs into vascular cells including endothelial
      cells (ECs) and vascular smooth muscle cells (SMCs). In the present study, we
      investigated the role of miR-145 in the differentiation process from human ESCs
      into ECs and SMCs. METHODS AND RESULTS: Undifferentiated human ESCs were induced
      to differentiate into vascular lineage according to our established method.
      Quantitative RT-PCR analysis revealed that human ESC-derived precursor of SMCs
      (ES-pre-SMCs), similar to human aortic SMCs, expressed a significant amount of
      miR-145 as well as smooth muscle-specific proteins, compared to undifferentiated
      human ESCs, adult ECs, or ESC-derived ECs (ES-ECs). However, morphological
      analysis revealed that human ES-pre-SMCs appeared round and flattened in shape,
      though human aortic SMCs exhibited the typical spindle-like morphology of SMCs.
      In addition, Kruppel-like factor 4 and 5 (KLF4 and 5), direct targets of miR-145
      and suppressors of smooth muscle differentiation, were upregulated in ES-pre-SMCs
      compared to aortic SMCs, indicating ES-pre-SMCs were not fully differentiated
      SMCs. Overexpression of miR-145 in ES-pre-SMCs upregulated the expression of
      smooth muscle markers, repressed KLF4 and 5 expressions, and changed their
      morphology into a differentiated spindle-like shape. Furthermore, by introduction
      of miR-145, ES-pre-SMC proliferation was significantly inhibited and carbachol
      stimulated contraction of ES-pre-SMCs was significantly increased. In contrast,
      downregulation of miR-145 in ES-pre-SMCs upregulated KLF4 and 5 expressions,
      suppressed the expression of smooth muscle markers, and left unchanged their
      proliferation and contractility. In ES-ECs, miR-145 overexpression did not induce
      the synthesis of smooth muscle-related proteins nor suppress the expression of
      endothelial nitric oxide synthase. CONCLUSION: We showed that miR-145 can
      regulate the fate and phenotype of human ES-pre-SMCs as they become fully
      differentiated SMCs. Overexpression of miR-145 on human ES-pre-SMCs is a
      promising method to obtain functional mature SMCs from human ESCs, which are
      required for reliable experimental research in the fields of atherosclerosis,
      hypertension and other vascular diseases.

PMID- 21945501
TI  - Derived morphology in a basal moth: The uniquely specialized sternum V glands of
      Agathiphaga (Lepidoptera: Agathiphagidae).
AB  - The sternum V gland is a notable specialization shared by basal Lepidoptera and
      most Trichoptera; it is generally present in both sexes or in females only. In
      both orders the secretory cells usually discharge into a sac-like reservoir from
      which a duct leads to the opening on sternum V. In contrast, the gland in
      agathiphagid moths is only present in males and it exhibits several unique
      specialisations: the glandular portion being the apical (morphologically
      anterior) part of a long tubular cuticular invagination covered with contiguous
      'type-3' glandular units; together with the following part of the efferent duct
      it is coiled like a ball of yarn; the duct expands into a fusiform reservoir, and
      a separate small sac surrounded by a complex muscular coat is present just inside
      the gland opening. The principal opener muscle of each gland originates on the
      contralateral side of sternum VI, hence crossing its counterpart in the midline.
      Characters of the agathiphagid sternum V gland, the function of which remains
      unclear (though sex pheromone production may appear most likely), add
      significantly to the suite of autapomorphies exhibited by this otherwise overall
      remarkably generalized moth taxon.

PMID- 21945502
TI  - Regulatory design in a simple system integrating membrane potential generation
      and metabolic ATP consumption. Robustness and the role of energy dissipating
      processes.
AB  - Bacterial physiological responses integrate energy-coupling processes at the
      membrane level with metabolic energy demand. The regulatory design behind these
      responses remains largely unexplored. Propionigenium modestum is an adequate
      organism to study these responses because it presents the simplest scheme known
      integrating membrane potential generation and metabolic ATP consumption. A
      hypothetical sodium leak is added to the scheme as the sole regulatory site.
      Allosteric regulation is assumed to be absent. Information of the rate equations
      is not available. However, relevant features of the patterns of responses may be
      obtained using Metabolic Control Analysis (MCA) and Metabolic Control Design
      (MCD). With these tools, we show that membrane potential disturbances can be
      compensated by adjusting the leak flux, without significant perturbations of ATP
      consumption. Perturbations of membrane potential by ATP demand are inevitable and
      also require compensatory changes in the leak. Numerical simulations were
      performed with a kinetic model exhibiting the responses for small changes
      obtained with MCA and MCD. A modest leak (10% of input) was assumed for the
      reference state. We found that disturbances in membrane potential and ATP
      consumption, produced by environmental perturbations of the cation concentration,
      may be reverted to the reference state adjusting the leak. Leak changes can also
      compensate for undesirable effects on membrane potential produced by changes in
      nutrient availability or ATP demand, in a wide range of values. The system is
      highly robust to parameter fluctuations. The regulatory role of energy
      dissipating processes and the trade-off between energetic efficiency and
      regulatory capacity are discussed.

PMID- 21945503
TI  - Magnetic resonance angiography demonstrating active spontaneous intercostal
      bleeding.

PMID- 21945504
TI  - The combined vaginal contraceptive ring, nuvaring, and cerebral venous sinus
      thrombosis: a case report and review of the literature.
AB  - BACKGROUND: Combined oral contraceptives are known to confer a risk of venous
      thromboembolism, including cerebral venous sinus thrombosis (CVST), to otherwise
      healthy women. NuvaRing (Organon USA, Inc., Roseland, NJ) is a contraceptive
      vaginal ring that delivers 120 MUg of etonogestrel and 15 MUg of ethinyl
      estradiol per day. Its use has been associated with rare venous thromboembolic
      events, but few cases of CVST associated with NuvaRing have been reported.
      OBJECTIVE: To describe a case that illustrates the increased risk of CVST
      associated with use of NuvaRing. We describe the case of a NuvaRing user who
      presented to our emergency department with a headache, who was diagnosed with
      CVST. CONCLUSION: Evidence suggests that NuvaRing has at least as much
      prothrombotic potential as combined oral contraceptives. Thus, emergency
      physicians should suspect serious venous thromboembolic events, including CVST,
      deep venous thrombosis, and pulmonary embolism, in NuvaRing users in the proper
      clinical setting.

PMID- 21945505
TI  - Emergency medicine Joint Fellowship Curriculum.
AB  - BACKGROUND: The authors describe a Joint Fellowship Curriculum instituted for
      emergency medicine fellows in diverse fellowships. The curriculum is based on
      commonalities established among the varying fellowships offered within their
      Department of Emergency Medicine. Fellowships included in the curriculum
      development include Disaster/Emergency Medical Services, International Emergency
      Medicine, Health Policy, Ultrasonography, and Medical Toxicology. OBJECTIVES: The
      focus of this educational activity is to promote the development of the fellow
      into an expert within their field of specialization. DISCUSSION: Recognizing that
      topics such as scholarly activities, career development, clinical practice of
      medicine, business of medicine, and personal development are universally
      applicable to a variety of emergency medicine fellowships, the curriculum
      attempts to provide uniform instruction. The quality and applicability of this
      instruction was assessed and found to have been very well received by the
      participating fellows. CONCLUSION: The authors encourage academic emergency
      medicine departments with a number of fellowship training opportunities to
      consider providing such a uniform curriculum of instruction as well.

PMID- 21945506
TI  - Pneumatosis intestinalis on plain film.

PMID- 21945507
TI  - TASER((r)) injury to the forehead.

PMID- 21945508
TI  - Reporter-Interpreter-Manager-Educator (RIME) descriptive ratings as an evaluation
      tool in an emergency medicine clerkship.
AB  - BACKGROUND: Emergency Medicine (EM) clerkships traditionally assess students
      using numerical ratings of clinical performance. The descriptive ratings of the
      Reporter, Interpreter, Manager, and Educator (RIME) method have been shown to be
      valuable in other specialties. OBJECTIVES: We hypothesized that the RIME
      descriptive ratings would correlate with clinical performance and examination
      scores in an EM clerkship, indicating that the RIME ratings are a valid measure
      of performance. METHODS: This was a prospective cohort study of an evaluation
      instrument for 4(th)-year medical students completing an EM rotation. This study
      received exempt Institutional Review Board status. EM faculty and residents
      completed shift evaluation forms including both numerical and RIME ratings.
      Students completed a final examination. Mean scores for RIME and clinical
      evaluations were calculated. Linear regression models were used to determine
      whether RIME ratings predicted clinical evaluation scores or final examination
      scores. RESULTS: Four hundred thirty-nine students who completed the EM clerkship
      were enrolled in the study. After excluding items with missing data, there were
      2086 evaluation forms (based on 289 students) available for analysis. There was a
      clear positive relationship between RIME category and clinical evaluation score
      (r(2)=0.40, p<0.01). RIME ratings correlated most strongly with patient
      management skills and least strongly with humanistic qualities. A very weak
      correlation was seen with RIME and final examination. CONCLUSION: We found a
      positive association between RIME and clinical evaluation scores, suggesting that
      RIME is a valid clinical evaluation instrument. RIME descriptive ratings can be
      incorporated into EM evaluation instruments and provides useful data related to
      patient management skills.

PMID- 21945509
TI  - Aborted myocardial infarction in a patient with rapid progression of Wellens
      syndrome.
AB  - BACKGROUND: Wellens syndrome refers to a distinct electrocardiographic pattern of
      deeply inverted or biphasic T waves in the anterior precordial leads, in the
      presence of critical proximal stenosis of the left anterior descending coronary
      artery (LAD). The natural history of the syndrome is an extensive myocardial
      infarction within weeks of hospital admission. CASE REPORT: This report describes
      a 63-year-old man in whom typical electrocardiographic signs of Wellens syndrome
      advanced to persistent ST-segment elevation within 7min of presentation.
      Extensive anterior myocardial infarction (AMI) was aborted by primary
      percutaneous coronary intervention of a sub-occluded proximal LAD. CONCLUSION:
      Given the large area of the left ventricle supplied by a sub-occluded LAD,
      devastating AMI could have been expected and may have resulted in serious
      ventricular dysfunction and death. Therefore, early recognition of Wellens
      syndrome is essential and can be lifesaving.

PMID- 21945510
TI  - [Laparoscopy coupled with classical abdominoplasty in 10 cases of large rectus
      diastasis].
AB  - In 10 cases of abdominoplasty where an important rectus diastasis had to be
      corrected, we completed the plication of the rectus sheath included in a
      classical abdominoplasty with the laparoscopic positioning of an intraperitoneal
      prosthesis. PURPOSE: To assess the middle-term results of this technique and
      present its advantages and drawbacks. PATIENTS AND METHOD: Fifteen patients have
      been operated from 2007 to 2011 by two surgeon teams. Ten of them have accepted
      to be included in our survey. RESULTS: All the patients said they were satisfied
      with their surgery. Four of them reported mild pain during the first
      postoperative weeks, and two of them mentioned very moderate pain at the time of
      the survey. The surgeons were not satisfied with the results obtained in two
      cases. Only one of these two patients accepted revision abdominoplasty with a
      good result. CONCLUSION: Laparoscopic positioning of an intraperitoneal
      prosthesis, coupled with a classical plication of the rectus sheath, gives
      excellent results in difficult cases of rectus diastasis.

PMID- 21945511
TI  - The efficacy and tolerability of MK-0633, a 5-lipoxygenase inhibitor, in chronic
      asthma.
AB  - Leukotriene B4 (LTB(4)) is a potent inflammatory mediator in asthma, and is
      increased in more severe asthma. Targeting LTB(4), in addition to cysteinyl
      leukotrienes, could be beneficial in asthma. This was a randomized, double-blind
      trial of once-daily MK-0633, a potent 5-lypoxygenase inhibitor, 10 mg, 50 mg, and
      100 mg, and placebo in patients 18-70 years with a history of chronic asthma, and
      FEV(1) >=45 and <=85% predicted. There was a 6-week main period and optional 18
      week and 34-week periods (52 weeks total), the latter two comparing only MK-0633
      100 mg and placebo. The primary endpoint was the change from baseline in FEV(1)
      over the last 4 weeks of the 6-week primary treatment period. Secondary endpoints
      included symptom scores, beta-agonist use, peak expiratory flow (PEF), asthma
      quality of life questionnaire (AQLQ), asthma control questionnaire (ACQ), asthma
      attacks, exacerbations, days with asthma control, post-beta-agonist FEV(1), and
      blood eosinophils. MK-0633 100 mg was significantly more effective than placebo
      for the change from baseline in FEV(1) (0.20 L vs. 0.13 L; p = 0.004). The other
      MK-0633 doses were not significantly more effective than placebo. MK-0633 (at
      various doses) was also more effective than placebo for beta-agonist use, AQLQ,
      AM and PM PEFR, ACQ, and post-beta-agonist FEV(1) (p < 0.05 for all). MK-0633 was
      associated with a dose-dependent increase in elevated aspartate aminotransferase
      and alanine aminotransferase. Because of the relative benefit-risk ratio, the
      optional study periods were terminated after unblinding for the main study
      period. Overall, the benefit-risk ratio did not support the clinical utility of
      MK-0633 in asthma.

PMID- 21945512
TI  - Case-matched comparison of early and long-term outcomes of everted cervical vein
      and saphenous vein carotid patch angioplasty.
AB  - OBJECTIVES: To compare outcomes after carotid endarterectomy (CEA) with saphenous
      vein patch closure (SV), with cervical vein (external jugular and common facial)
      patch closure (CV). DESIGN: A total of 322 cases of CEA was achieved
      consecutively by using venous patch angioplasty. Propensity scores were
      calculated followed by a one-to-one basis case-matching. MATERIALS: This resulted
      into 90 SV and 90 CV matched cases. METHODS: The primary endpoint was the
      incidence of ipsilateral stroke and transient ischaemic attack at any time during
      follow-up. RESULTS: Ten-year freedom from stroke was 94.1% +/- 3.5% for the SV
      group and 90.5% +/- 4.2% for the CV group (log rank P = 0.230). Ten-year freedom
      from ipsilateral neurological events (stroke and transient ischaemic attack) was
      93.5% +/- 3.3% for SV group and 92.4% +/- 3.0% for the CV group (log rank P =
      0.403). Ten-year freedom from >=75% stenosis/occlusion was 93.1 +/- 4.8% for the
      SV group and 89.9 +/- 6.0% for the CV group (log rank P = 0.481). CONCLUSIONS: CV
      is a good alternative to SV patching, particularly when the SV needs to be
      preserved for further use or is unsuitable.

PMID- 21945513
TI  - Re: Prospective evaluation of operating characteristics of prostate cancer
      detection biomarkers: Y. Liang, D. P. Ankerst, N. S. Ketchum, B. Ercole, G. Shah,
      J. D. Shaughnessy, Jr., R. J. Leach and I. M. Thompson J Urol 2011; 185: 104-110.

PMID- 21945515
TI  - The complex landscape of genetic alterations in mantle cell lymphoma.
AB  - Mantle cell lymphoma (MCL) is genetically characterized by the t(11;14)(q13;q32)
      which deregulates cyclin D1. Small subsets of cases have been identified with
      variant CCND1 translocations with the immunoglobulin light chain genes or with
      alternative translocations involving CCND2 and CCND3. Additionally, double-hit
      MCL with MYC rearrangements with a highly aggressive clinical course have been
      reported, but no other frequent recurrent translocations have been identified. In
      recent years, genome-wide screening of copy number alterations by comparative
      genomic hybridization and genomic microarray platforms have revealed a
      characteristic MCL profile of multiple secondary gains and losses as well as
      regions of copy number neutral loss of heterozygosity that target mainly genes
      involved in cell cycle regulation, DNA damage response, and cell survival
      pathways. Several aberrations have been found to be associated with worse
      prognosis, 3q gains and losses of 8p, 9p, and 17p. An increased number of
      secondary alterations and blastoid morphology have also been shown to be
      associated with cases with short survival. On the contrary, indolent MCL cases
      carry only the primary t(11;14) and few or no other additional genomic
      alterations. Altogether these observations suggest that the genetic background of
      MCL is an important factor that dictates their different clinical behavior. This
      review will focus on MCL from a genetic perspective and will present next
      generation sequencing technology as a new potential tool to complement the study
      of complex genomes. The better understanding of genetic alterations of MCL may
      offer new approaches for more patient-tailored, risk-adapted treatment options.

PMID- 21945516
TI  - The microenvironment in mantle cell lymphoma: cellular and molecular pathways and
      emerging targeted therapies.
AB  - There is growing evidence suggesting that cross talk between mantle cell lymphoma
      (MCL) cells and stromal cells in tissue microenvironments, such as the bone
      marrow and secondary lymphoid organs, causes disease progression by promoting
      lymphoma cell survival, growth, and drug resistance. Conceivably, while
      conventional treatment eliminates the bulk of MCL cells, residual lymphoma cells
      may lurk in protective tissue niches, where they receive signals from accessory
      cells that promote survival and drug-resistance, thereby paving the way for
      residual disease and relapses. Based on this concept, the lymphoma
      microenvironment has become a growing area of current research, and initial
      clinical trials targeting cross talk between MCL cells and their microenvironment
      are showing promising early results. In this review, we summarize key cellular
      and molecular interactions between MCL cells and their microenvironment, and
      update new clinical developments in this area.

PMID- 21945518
TI  - Epidemiology and etiology of mantle cell lymphoma and other non-Hodgkin lymphoma
      subtypes.
AB  - We aimed to give an overview of the descriptive epidemiology and etiology of
      mantle cell lymphoma (MCL) in the context of all non-Hodgkin lymphoma (NHL) and
      major NHL subtypes, based on available published reports. In retrospective case
      series, MCL cases represent between 2 and 10% of all NHL. Population-based
      studies of MCL incidence by basic demographic characteristics are limited to the
      past 15-20 years and to Europe and the US. In both regions, average incidence
      rates of approximately 0.5 cases per 100,000 person-years were reported, with a
      male-to-female ratio of 2.3-2.5:1, and a median age at diagnosis of close to 70
      years. Some data suggest a possible increase in MCL incidence over the last two
      decades, but the observation may also reflect improved diagnostics. The causes of
      MCL are not known. Studies of potential risk factors of MCL are few and conducted
      primarily within the framework of all NHL. Moderate associations with MCL risk
      have been reported for Borrelia burgdorferi infection, family history of
      hematopoietic malignancies, and genetic variation in the interleukin-10 and tumor
      necrosis factor genes, but findings remain unconfirmed. Large multicenter studies
      are needed to address these and other factors in risk of MCL with sufficient
      statistical power in the future.

PMID- 21945517
TI  - New molecular targets in mantle cell lymphoma.
AB  - Mantle cell lymphoma (MCL) is a malignancy of mature B cells characterized by
      aberrant expression of cyclin D1 due to the translocation t(11;14). Epigenomic
      and genomic lesions in pathways regulating B-cell activation, cell cycle
      progression, protein homeostasis, DNA damage response, cell proliferation and
      apoptosis contribute to its pathogenesis. While patients typically respond to
      first-line chemotherapy, relapse is the rule resulting in a median survival of 5
      7 years. The PI3K/AKT/mTOR appears as a key pathway in the pathogenesis and can
      be targeted with small molecules. Most experience is with mTOR inhibitors of the
      rapamycin class. Second-generation mTOR inhibitors and the PI3K inhibitor CAL-101
      are novel options to more effectively target this pathway. Bruton's tyrosine
      kinase inhibition by PCI-32765 has promising activity and indicates
      immunoreceptor signaling as a novel therapeutic target. Up to 50% of relapsed
      patients respond to the proteasome inhibitor bortezomib suggesting that MCL may
      be particularly sensitive to disruption of protein homeostasis and/or induction
      of oxidative stress. Recent work has focused on elucidating the mechanism of
      bortezomib-induced cytotoxicity and the development of second-generation
      proteasome inhibitors. DNA hypomethylating agents and histone deacetylase
      inhibitors effect epigenetic de-repression of aberrantly silenced genes. These
      epigenetic pharmaceuticals and HSP90 inhibitors can synergize with proteasome
      inhibitors. Finally, BH3 mimetics are emerging as tools to sensitize tumor cells
      to chemotherapy. Participation in clinical trials offers patients a chance to
      benefit from these advances and is essential to maintain the momentum of
      progress. Innovative trial designs may be needed to expedite the clinical
      development of these targeted agents.

PMID- 21945519
TI  - Ontogenic changes in placental transthyretin.
AB  - OBJECTIVES: Before secretion of fetal thyroid hormone at around 16 weeks
      gestation normal fetal development depends on a constant supply of maternal
      thyroid hormone (TH), particularly thyroxine (T(4)). The detailed mechanisms of
      transplacental delivery of TH are still uncertain. The TH binding protein,
      transthyretin (TTR), is produced and secreted by placenta and may play a role in
      this process. The ontogeny of placental TTR is unknown. Our aim was to study
      changes in placental TTR in early and late pregnancy. STUDY DESIGN: We collected
      placentas from surgically terminated pregnancies between 6 and 17 weeks gestation
      (n = 44) and from normal term (38-39 weeks) pregnancies following caesarean
      section (n = 5). Real time-PCR, western blotting and immunohistochemistry were
      used to determine TTR mRNA and protein levels. RESULTS: There were highly
      significant correlations between gestational age and TTR mRNA (r = 0.974; p <
      0.0001) and between gestational age and TTR protein (r = 0.901; p < 0.001) levels
      between weeks 6 and 13 of gestation. TTR expression did not increase between 13
      and 17 weeks and was not different at term. Good correlation was observed between
      TTR mRNA and TTR protein between individual placental samples (r = 0.916; p <
      0.0001). A similar trend was observed using immunohistochemical staining of
      placental paraffin sections. CONCLUSIONS: Our results demonstrate that TTR is
      expressed in the human placenta from at least 6 weeks gestation. Levels rise
      during the first trimester at a time when placental oxygen tensions are also
      rising. We hypothesise that TTR production and secretion by the placenta may
      facilitate transplacental delivery of TH to the fetus.

PMID- 21945520
TI  - Mitochondrial adenine nucleotide transport and cardioprotection.
AB  - Mitochondria are highly metabolically active cell organelles that not only act as
      the powerhouse of the cell by supplying energy through ATP production, but also
      play a destructive role by initiating cell death pathways. Growing evidence
      recognizes that mitochondrial dysfunction is one of the major causes of
      cardiovascular disease. Under de-energized conditions, slowing of adenine
      nucleotide transport in and out of the mitochondria significantly attenuates
      myocardial ischemia-reperfusion injury. The purpose of this review is to
      elaborate on and update the mechanistic pathways which may explain how altered
      adenine nucleotide transport can influence cardiovascular function. This article
      is part of a Special Issue entitled "Local Signaling in Myocytes".

PMID- 21945522
TI  - A direct neuronal connection between the telencephalic nucleus robustus
      arcopallialis and the nucleus nervi hypoglossi, pars tracheosyringealis in
      Bengalese finches (Lonchura striata var. domestica).
AB  - Bird species with vocal learning possess a projection from the telencephalic
      nucleus to the nucleus nervi hypoglossi, pars tracheosyringealis (XIIts) in the
      medulla, where a final common pathway that controls the vocal organ, i.e., the
      synrinx, originates. The anatomical basis of this projection has not been well
      investigated in one species of songbird, the Bengalese finch (Lonchura striata
      var. domestica). The present study used anterograde and retrograde tracing
      experiments to examine and describe this projection in Bengalese finches.
      Following iontophoretic injections of biotinylated dextran amine into the
      telencephalic nucleus robustus arcopallialis (RA), we detected anterograde
      labeled terminations in the XIIts. In addition, labeled terminals were seen in
      other vocal-respiratory-related nuclei, such as the dorsomedial nucleus of the
      nucleus intercollicularis, nucleus infraolivaris superior, nucleus of the rostral
      ventrolateral medulla, nucleus parambigualis, nucleus ambiguous, and nucleus
      retroambigualis. Furthermore, following injections into the XIIts, we detected
      retrograde-labeled cell bodies scattered throughout the ipsilateral RA. The
      present results revealed that the direct projections of the RA to the XIIts in
      male Bengalese finches are similar to those in other songbirds with vocal
      learning abilities.

PMID- 21945523
TI  - Regulation and functions of the lipid kinase PIP5K g661 at synapses.

PMID- 21945521
TI  - Redox modification of cell signaling in the cardiovascular system.
AB  - Oxidative stress is presumed to be involved in the pathogenesis of many diseases,
      including cardiovascular disease. However, oxidants are also generated in healthy
      cells, and increasing evidence suggests that they can act as signaling molecules.
      The intracellular reduction-oxidation (redox) status is tightly regulated by
      oxidant and antioxidant systems. Imbalance between them causes oxidative or
      reductive stress which triggers cellular damage or aberrant signaling, leading to
      dysregulation. In this review, we will briefly summarize the aspects of ROS
      generation and neutralization mechanisms in the cardiovascular system. ROS can
      regulate cell signaling through oxidation and reduction of specific amino acids
      within proteins. Structural changes during post-translational modification allow
      modification of protein activity which can result in altered cellular function.
      We will focus on the molecular basis of redox protein modification and how this
      regulatory mechanism affects signal transduction in the cardiovascular system.
      Finally, we will discuss some techniques applied to monitoring redox status and
      identifying redox-sensitive proteins in the heart. This article is part of a
      Special Section entitled "Post-translational Modification."

PMID- 21945524
TI  - The activity, evolution and association of phosphatidylinositol 5-phosphate 4
      kinases.

PMID- 21945525
TI  - Anthraquinone compounds from Morinda officinalis inhibit osteoclastic bone
      resorption in vitro.
AB  - The root of Morinda officinalis has been claimed to have a protective effect
      against bone loss in sciatic neurectomized and ovariectomized osteoporotic rats,
      and this protective effect is supposed to be attributed to anthraquinone
      compounds in the plant. In the present study, we investigated the effects of
      three anthraquinones isolated from M. officinalis, including 1, 3, 8-trihydroxy-2
      methoxy-anthraquinone (1), 2-hydroxy-1-methoxy-anthraquinone (2) and rubiadin (3)
      on bone resorption activity in vitro and the mechanism on osteoclasts derived
      from rat bone marrow cells. Compound 1, 2 and 3 decreased the formation of bone
      resorption pits, the number of multinucleated osteoclasts, and the activity of
      tartrate resistant acid phosphates (TRAP) and cathepsin K in the coculture system
      of osteoblasts and bone marrow cells in the presence of 1, 25-dihydroxyvitamine
      D(3) and dexamethasone. They also enhanced the apoptosis of osteoclasts induced
      from bone marrow cells with M-CSF and RANKL. In addition, Compound 1, 2 and 3
      improved the ratio of mRNA and protein expression of OPG and RANKL in
      osteoblasts, interfered with the JNK and NF-kappaB signal pathway, and reduced
      the expression of calcitonin receptor (CTR) and carbonic anhydrase/II (CA II) in
      osteoclasts induced from bone marrow cells with M-CSF and RANKL. These findings
      indicate that the anthraquinone compounds from M. officinalis are potential
      inhibitors of bone resorption, and may also serve as evidence to explain the
      mechanism of the inhibitory effects of some other reported anthraquinones on bone
      loss.

PMID- 21945526
TI  - Structural change in beta-sheet A of Z alpha(1)-antitrypsin is responsible for
      accelerated polymerization and disease.
AB  - The presence of the Z mutation (Glu342Lys) is responsible for more than 95% of
      alpha(1)-antitrypsin (alpha(1)AT) deficiency cases. It leads to increased
      polymerization of the serpin alpha(1)AT during its synthesis and in circulation.
      It has been proposed that the Z mutation results in a conformational change
      within the folded state of antitrypsin that enhances its polymerization. In order
      to localize the conformational change, we have created two single tryptophan
      mutants of Z alpha(1)AT and analyzed their fluorescence properties. alpha(1)AT
      contains two tryptophan residues that are located in distinct regions of the
      molecule: Trp194 at the top of beta-sheet A and Trp238 on beta-sheet B. We have
      replaced each tryptophan residue individually with a phenylalanine in order to
      study the local environment of the remaining tryptophan residue in both M and Z
      alpha(1)AT. A detailed fluorescence spectroscopic analysis of each mutant was
      carried out, and we detected differences in the emission spectrum, the Stern
      Volmer constant for potassium iodide quenching and the anisotropy of only Trp194
      in Z alpha(1)AT compared to M alpha(1)AT. Our data reveal that the Z mutation
      results in a conformational change at the top of beta-sheet A but does not affect
      the structural integrity of beta-sheet B.

PMID- 21945527
TI  - Reengineering Cro protein functional specificity with an evolutionary code.
AB  - Cro proteins from different lambdoid bacteriophages are extremely variable in
      their target consensus DNA sequences and constitute an excellent model for
      evolution of transcription factor specificity. We experimentally tested a
      bioinformatically derived evolutionary code relating switches between pairs of
      amino acids at three recognition helix sites in Cro proteins to switches between
      pairs of nucleotide bases in the cognate consensus DNA half-sites. We generated
      all eight possible code variants of bacteriophage lambda Cro and used
      electrophoretic mobility shift assays to compare binding of each variant to its
      own putative cognate site and to the wild-type cognate site; we also tested the
      wild-type protein against all eight DNA sites. Each code variant showed stronger
      binding to its putative cognate site than to the wild-type site, except some
      variants containing proline at position 27; each also bound its cognate site
      better than wild-type Cro bound the same site. Most code variants, however,
      displayed poorer affinity and specificity than wild-type lambda Cro. Fluorescence
      anisotropy assays on lambda Cro and the triple code variant (PSQ) against the two
      cognate sites confirmed the switch in specificity and showed larger apparent
      effects on binding affinity and specificity. Bacterial one-hybrid assays of
      lambda Cro and PSQ against libraries of sequences with a single randomized half
      site showed the expected switches in specificity at two of three coded positions
      and no clear switches in specificity at noncoded positions. With a few caveats,
      these results confirm that the proposed Cro evolutionary code can be used to
      reengineer Cro specificity.

PMID- 21945528
TI  - Functional characterization of Fdx1: evidence for an evolutionary relationship
      between P450-type and ISC-type ferredoxins.
AB  - Ferredoxins are ubiquitous proteins with electron transfer activity involved in a
      variety of biological processes. In this work, we investigated the
      characteristics and function of Fdx1 from Sorangium cellulosum So ce56 by using a
      combination of bioinformatics and of biochemical/biophysical approaches. We were
      able to experimentally confirm a role of Fdx1 in the iron-sulfur cluster
      biosynthesis by in vitro reduction studies with cluster-loaded So ce56 IscU and
      by transfer studies of the cluster from the latter protein to apo-aconitase A.
      Moreover, we found that Fdx1 can replace mammalian adrenodoxin in supporting the
      activity of bovine CYP11A1. This makes S. cellulosum Fdx1 the first prokaryotic
      ferredoxin reported to functionally interact with this mammalian enzyme. Although
      the interaction with CYP11A1 is non-physiological, this is-to the best of our
      knowledge-the first study to experimentally prove the activity of a postulated
      ISC-type ferredoxin in both the ISC assembly and a cytochrome P450 system. This
      proves that a single ferredoxin can be structurally able to provide electrons to
      both cytochromes P450 and IscU and thus support different biochemical processes.
      Combining this finding with phylogenetic and evolutionary trace analyses led us
      to propose the evolution of eukaryotic mitochondrial P450-type ferredoxins and
      ISC-type ferredoxins from a common prokaryotic ISC-type ancestor.

PMID- 21945529
TI  - Analysis of binding site hot spots on the surface of Ras GTPase.
AB  - We have recently discovered an allosteric switch in Ras, bringing an additional
      level of complexity to this GTPase whose mutants are involved in nearly 30% of
      cancers. Upon activation of the allosteric switch, there is a shift in helix
      3/loop 7 associated with a disorder to order transition in the active site. Here,
      we use a combination of multiple solvent crystal structures and computational
      solvent mapping (FTMap) to determine binding site hot spots in the "off" and "on"
      allosteric states of the GTP-bound form of H-Ras. Thirteen sites are revealed,
      expanding possible target sites for ligand binding well beyond the active site.
      Comparison of FTMaps for the H and K isoforms reveals essentially identical hot
      spots. Furthermore, using NMR measurements of spin relaxation, we determined that
      K-Ras exhibits global conformational dynamics very similar to those we previously
      reported for H-Ras. We thus hypothesize that the global conformational
      rearrangement serves as a mechanism for allosteric coupling between the effector
      interface and remote hot spots in all Ras isoforms. At least with respect to the
      binding sites involving the G domain, H-Ras is an excellent model for K-Ras and
      probably N-Ras as well. Ras has so far been elusive as a target for drug design.
      The present work identifies various unexplored hot spots throughout the entire
      surface of Ras, extending the focus from the disordered active site to well
      ordered locations that should be easier to target.

PMID- 21945530
TI  - The rate of polyQ-mediated aggregation is dramatically affected by the number and
      location of surrounding domains.
AB  - The nine polyglutamine (polyQ) neurodegenerative diseases are caused in part by a
      gain-of-function mechanism involving protein misfolding, the deposition of beta
      sheet-rich aggregates and neuronal toxicity. While previous experimental evidence
      suggests that the polyQ-induced misfolding mechanism is context dependent, the
      properties of the host protein, including the domain architecture and location of
      the polyQ tract, have not been investigated. Here, we use variants of a model
      polyQ-containing protein to systematically determine the effect of the location
      and number of flanking folded domains on polyQ-mediated aggregation. Our data
      indicate that when a pathological-length polyQ tract is present between two
      domains, it aggregates more slowly than the same-length tract in a terminal
      location within the protein. We also demonstrate that increasing the number of
      flanking domains decreases the polyQ protein's aggregation rate. Our experimental
      data, together with a bioinformatic analysis of all human proteins possessing
      polyQ tracts, suggest that repeat location and protein domain architecture affect
      the disease susceptibility of human polyQ proteins.

PMID- 21945531
TI  - Composition and topology of the endoplasmic reticulum-mitochondria encounter
      structure.
AB  - Eukaryotic cells contain multiple organelles, which are functionally and
      structurally interconnected. The endoplasmic reticulum-mitochondria encounter
      structure (ERMES) forms a junction between mitochondria and the endoplasmic
      reticulum (ER). Four ERMES proteins are known in yeast, the ER-anchored protein
      Mmm1 and three mitochondria-associated proteins, Mdm10, Mdm12 and Mdm34, with
      functions related to mitochondrial morphology and protein biogenesis. We mapped
      the glycosylation sites of ERMES and demonstrate that three asparagine residues
      in the N-terminal domain of Mmm1 are glycosylated. While the glycosylation is
      dispensable, the cytosolic C-terminal domain of Mmm1 that connects to the Mdm
      proteins is required for Mmm1 function. To analyze the composition of ERMES, we
      determined the subunits by quantitative mass spectrometry. We identified the
      calcium-binding GTPase Gem1 as a new ERMES subunit, revealing that ERMES is
      composed of five genuine subunits. Taken together, ERMES represents a platform
      that integrates components with functions in formation of ER-mitochondria
      junctions, maintenance of mitochondrial morphology, protein biogenesis and
      calcium binding.

PMID- 21945533
TI  - Resolving phylogenetic signal from noise when divergence is rapid: a new look at
      the old problem of echinoderm class relationships.
AB  - Resolving evolutionary relationships in groups that underwent fast radiation in
      deep time is a problem for molecular phylogeny, as the scant phylogenetic signal
      that characterises short internal branches is generally swamped by more recent
      substitutions. We implement an approach, that maps how the support for rival
      phylogenies changes when analysing subsets of sites with either faster and more
      heterogeneous rates or slower and more homogeneous rates, to address a long
      standing problem in deuterostome phylogeny - the interrelationships of the
      eleutherozoan echinoderm classes. We show that miRNA genes are phylogenetically
      uninformative as to the relationships of asteroids, echinoids and ophiuroids,
      consistent with a rapid radiation of these groups as suggested by their fossil
      record. Using three nuclear rRNAs and seven nuclear housekeeping genes, we map
      the support for the three possible phylogenetic arrangements of asteroids,
      ophiuroids and echinoids when moving between subsets of the data with very
      similar or very different rates of evolution. Only one of the three possible
      topologies (asteroids (ophiuroids+echinoids)) strengthens when the most rate
      homogeneous subset of data are analysed. The other two possible pairings become
      stronger in a less reliable data subset, which includes the fastest and thus
      homoplasy-rich data in our alignment. Thus, while superficial analysis of our
      concatenated alignment identifies asteroids and ophiuroids as sister taxa, more
      thorough analyses suggest that ophiuroids may be more closely related to
      echinoids. Divergence of these echinoderm groups, using a relaxed molecular
      clock, is estimated to have occurred within ~ 5 million years. Our results
      illustrate that the analytic approach of phylogenetic signal dissection can be a
      powerful tool to investigate rapid radiations in deep geologic time.

PMID- 21945532
TI  - High-throughput genetic identification of functionally important regions of the
      yeast DEAD-box protein Mss116p.
AB  - The Saccharomyces cerevisiae DEAD-box protein Mss116p is a general RNA chaperone
      that functions in splicing mitochondrial group I and group II introns. Recent X
      ray crystal structures of Mss116p in complex with ATP analogs and single-stranded
      RNA show that the helicase core induces a bend in the bound RNA, as in other DEAD
      box proteins, while a C-terminal extension (CTE) induces a second bend, resulting
      in RNA crimping. Here, we illuminate these structures by using high-throughput
      genetic selections, unigenic evolution, and analyses of in vivo splicing activity
      to comprehensively identify functionally important regions and permissible amino
      acid substitutions throughout Mss116p. The functionally important regions include
      those containing conserved sequence motifs involved in ATP and RNA binding or
      interdomain interactions, as well as previously unidentified regions, including
      surface loops that may function in protein-protein interactions. The genetic
      selections recapitulate major features of the conserved helicase motifs seen in
      other DEAD-box proteins but also show surprising variations, including multiple
      novel variants of motif III (SAT). Patterns of amino acid substitutions indicate
      that the RNA bend induced by the helicase core depends on ionic and hydrogen
      bonding interactions with the bound RNA; identify a subset of critically
      interacting residues; and indicate that the bend induced by the CTE results
      primarily from a steric block. Finally, we identified two conserved regions-one
      the previously noted post II region in the helicase core and the other in the CTE
      that may help displace or sequester the opposite RNA strand during RNA unwinding.

PMID- 21945534
TI  - Phylogenetic relationships elucidate colonization patterns in the intertidal
      grazers Osilinus Philippi, 1847 and Phorcus Risso, 1826 (Gastropoda: Trochidae)
      in the northeastern Atlantic Ocean and Mediterranean Sea.
AB  - Snails in the closely related trochid genera Phorcus Risso, 1826 and Osilinus
      Philippi, 1847 are ecologically important algal grazers in the intertidal zone of
      the northeastern Atlantic Ocean and Mediterranean Sea. Here we present the first
      complete molecular phylogeny for these genera, based on the nuclear 28S rRNA gene
      and the mitochondrial 16S rRNA and COI genes, and show that the current
      classification is erroneous. We recognize nine species in a single genus,
      Phorcus: estimated by BEAST analysis, this arose 30 (+/- 10) Ma; it consists of
      two subgenera, Phorcus and Osilinus, which we estimate diverged 14 (+/- 4.5) Ma.
      Osilinus kotschyi, from the Arabian and Red Seas, is not closely related and is
      tentatively referred to Priotrochus Fischer, 1879. Our phylogeny allows us to
      address biogeographical questions concerning the origins of the Mediterranean and
      Macaronesian species of this group. The former appear to have evolved from
      Atlantic ancestors that invaded the Mediterranean on several occasions after the
      Zanclean Flood, which ended the Messinian Salinity Crisis 5.3 Ma; whereas the
      latter arose from several colonizations of mainland Atlantic ancestors within the
      last 3 (+/- 1.5) Ma.

PMID- 21945535
TI  - Activation of cell-mediated immunity in depression: association with
      inflammation, melancholia, clinical staging and the fatigue and somatic symptom
      cluster of depression.
AB  - BACKGROUND: Depression is characterized by activation of cell-mediated immunity
      (CMI), including increased neopterin levels, and increased pro-inflammatory
      cytokines (PICs), such as interleukin-1 (IL-1) and tumor necrosis factor-alpha
      (TNFalpha). These PICs may induce depressive, melancholic and chronic fatigue
      (CF) symptoms. METHODS: We examined serum neopterin and plasma PIC levels in
      depressive subgroups in relation to the depressive subtypes and the melancholic
      and CF symptoms of depression. Participants were 85 patients with depression and
      in 26 normal controls. Severity of depression was assessed with the Hamilton
      Depression Rating Scale (HDRS) and severity of CF with the Fibromyalgia and
      Chronic Fatigue Syndrome (FF) Rating Scale. RESULTS: Serum neopterin was
      significantly higher in depressed patients and in particular in those with
      melancholia. There were positive correlations between serum neopterin, the plasma
      PICs and the number of previous depressive episodes. Neopterin and TNFalpha were
      associated with melancholia, while both PICs were associated with CF. Melancholia
      group membership was predicted by the HDRS and neopterin, and CF group membership
      by age, the FF score and serum TNFalpha. DISCUSSION: Depression and melancholia
      are accompanied by CMI activation, suggesting that neopterin plays a role in
      their pathophysiology, e.g. through activation of oxidative and nitrosative
      stress and apoptosis pathways. The intertwined CMI and inflammatory responses are
      potentially associated with the onset of depression and with the melancholic and
      CF symptoms of depression. Exposure to previous depressive episodes may magnify
      the size of CMI and PIC responses, possibly increasing the likelihood of new
      depressive episodes. CMI activation and inflammation may contribute to the
      staging or recurrence of depression.

PMID- 21945536
TI  - Site of death among veterans living in Veterans Affairs nursing homes.
AB  - OBJECTIVES: To determine predictors of dying in VA nursing homes, community
      living centers (CLCs), compared with dying in a hospital. DESIGN: Retrospective
      cohort study. SETTING: VA CLCs. PARTICIPANTS: Included were 7408 CLC decedents
      from FY2005 to FY2007. MEASUREMENTS:  OUTCOME: Site of death obtained from VA
      Vital Statistics files. Predictors of Death Site: VA-MDS variables defining
      patient demographics, functional status, cognitive status, major diagnostic
      categories, and care planning documentation. ANALYSIS: Logistic regression was
      used to estimate the odds ratio of death in the CLC relative to the hospital for
      patient and facility characteristics. RESULTS: Among decedents, 87% died in the
      CLC and 13% in a hospital. More than half of all decedents were neither enrolled
      in hospice nor designated as having end-stage disease. The strongest predictor of
      site of death in a CLC relative to a hospital was being enrolled in hospice (OR =
      20.94; 95% CI: 12.38, 35.44). A designation of end-stage disease increased the
      odds of death in a CLC by 3.9 times (95% CI: 2.78, 5.47) compared with death in a
      hospital. Advance directive rates in CLCs were high (73.4%); having any advance
      directive increased the odds of death in a CLC by 1.57 times (95% CI: 1.35,
      1.82). CONCLUSION: Recognition of end-stage disease and documentation of advance
      directives are powerful determinants of site of death for CLC residents. Receipt
      of hospice care in a CLC is a strong predictor of site of death in a CLC even in
      the absence of collaboration with community-based hospice and financial
      incentives to avoid hospitalization.

PMID- 21945537
TI  - Differential regulation of HCN channel isoform expression in thalamic neurons of
      epileptic and non-epileptic rat strains.
AB  - Hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels
      represent the molecular substrate of the hyperpolarization-activated inward
      current (I(h)). Although these channels act as pacemakers for the generation of
      rhythmic activity in the thalamocortical network during sleep and epilepsy, their
      developmental profile in the thalamus is not yet fully understood. Here we
      combined electrophysiological, immunohistochemical, and mathematical modeling
      techniques to examine HCN gene expression and I(h) properties in thalamocortical
      relay (TC) neurons of the dorsal part of the lateral geniculate nucleus (dLGN) in
      an epileptic (WAG/Rij) compared to a non-epileptic (ACI) rat strain. Recordings
      of TC neurons between postnatal day (P) 7 and P90 in both rat strains revealed
      that I(h) was characterized by higher current density, more hyperpolarized
      voltage dependence, faster activation kinetics, and reduced cAMP-sensitivity in
      epileptic animals. All four HCN channel isoforms (HCN1-4) were detected in dLGN,
      and quantitative analyses revealed a developmental increase of protein expression
      of HCN1, HCN2, and HCN4 but a decrease of HCN3. HCN1 was expressed at higher
      levels in WAG/Rij rats, a finding that was correlated with increased expression
      of the interacting proteins filamin A (FilA) and tetratricopeptide repeat
      containing Rab8b-interacting protein (TRIP8b). Analysis of a simplified computer
      model of the thalamic network revealed that the alterations of I(h) found in
      WAG/Rij rats compensate each other in a way that leaves I(h) availability
      constant, an effect that ensures unaltered cellular burst activity and thalamic
      oscillations. These data indicate that during postnatal developmental the
      hyperpolarizing shift in voltage dependency (resulting in less current
      availability) is compensated by an increase in current density in WAG/Rij thereby
      possibly limiting the impact of I(h) on epileptogenesis. Because HCN3 is
      expressed higher in young versus older animals, HCN3 likely does not contribute
      to alterations in I(h) in older animals.

PMID- 21945538
TI  - Effects of aromatase inhibition versus gonadectomy on hippocampal complex amyloid
      pathology in triple transgenic mice.
AB  - Alzheimer's disease (AD) is the most common form of dementia among the elderly
      with women exhibiting a higher risk than men for the disease. Due to these gender
      differences, there is great interest in the role that estrogens play in cognitive
      impairment and the onset of the classic amyloid and tau lesions in AD. Human and
      rodent studies indicate a strong association between low brain aromatase, sex
      hormone levels, and beta amyloid deposition. Therefore, the effects of depleting
      both circulating and brain estrogen levels, through gonadectomy and/or treatment
      with the aromatase inhibitor, anastrozole, upon hippocampal AD-like pathology in
      male and female 3xTgAD mice were evaluated. Liquid chromatography-mass
      spectrometry revealed anastrozole serum levels of 10.19 ng/mL and for the first
      time brain levels were detected at 4.7 pg/mL. Densitometric analysis of the
      hippocampus revealed that anastrozole significantly increased Abeta- but not
      APP/Abeta-immunoreactivity in intact 3xTgAD females compared to controls
      (p<0.001). Moreover, anastrozole significantly increased the number of Abeta-
      compared to APP/Abeta-positive hippocampal CA1 neurons in intact and
      gonadectomized female mice. Concurrently, anastrozole significantly reduced the
      APP/Abeta plaque load in 9 month old female 3xTgAD mice. These data suggest that
      anastrozole treatment differentially affects select amyloid species which in turn
      may play a role in the extraneuronal to intraneuronal deposition of this peptide.

PMID- 21945539
TI  - PINK1 enhances insulin-like growth factor-1-dependent Akt signaling and
      protection against apoptosis.
AB  - Mutations in the PARK6 gene coding for PTEN-induced kinase 1 (PINK1) cause
      recessive early-onset Parkinsonism. Although PINK1 and Parkin promote the
      degradation of depolarized mitochondria in cultured cells, little is known about
      changes in signaling pathways that may additionally contribute to dopamine neuron
      loss in recessive Parkinsonism. Accumulating evidence implicates impaired Akt
      cell survival signaling in sporadic and familial PD (PD). IGF-1/Akt signaling
      inhibits dopamine neuron loss in several animal models of PD and both IGF-1 and
      insulin are neuroprotective in various settings. Here, we tested whether PINK1 is
      required for insulin-like growth factor 1 (IGF-1) and insulin dependent
      phosphorylation of Akt and the regulation of downstream Akt target proteins. Our
      results show that embryonic fibroblasts from PINK1-deficient mice display
      significantly reduced Akt phosphorylation in response to both IGF-1 and insulin.
      Moreover, phosphorylation of glycogen synthase kinase-3beta (GSK-3beta) and
      nuclear exclusion of FoxO1 are decreased in IGF-1 treated PINK1-deficient cells.
      In addition, phosphorylation of ribosomal protein S6 is reduced indicating
      decreased activity of mitochondrial target of rapamycin (mTOR) in IGF-1 treated
      PINK1(-/-) cells. Importantly, the protection afforded by IGF-1 against
      staurosporine-induced metabolic dysfunction and apoptosis is abrogated in PINK1
      deficient cells. Moreover, IGF-1-induced Akt phosphorylation is impaired in
      primary cortical neurons from PINK1-deficient mice. Inhibition of cellular
      Ser/Thr phosphatases did not increase the amount of phosphorylated Akt in PINK1(
      /-) cells, suggesting that components upstream of Akt phosphorylation are
      compromised in PINK1-deficient cells. Our studies show that PINK1 is required for
      optimal IGF-1 and insulin dependent Akt signal transduction, and raise the
      possibility that impaired IGF-1/Akt signaling is involved in PINK1-related
      Parkinsonism by increasing the vulnerability of dopaminergic neurons to stress
      induced cell death.

PMID- 21945541
TI  - Dendrodendritic connections between the cochlear efferent neurons in guinea pig.
AB  - The outer hair cells of organ of Corti are innervated by the efferent neurons of
      medial olivocochlear neurons (MOC) of the brainstem which modify the cochlear
      auditory processing and sensitivity. Most of the MOC neurons are excited by a
      dominant ear and only a small portion of them is excited by both ears resulting
      in a binaural facilitation. The functional role of the feedback system between
      the organ of Corti and the cochlear efferent neurons is the protection of the ear
      from acoustic injury. The rapid impulse propagation in the bilateral
      olivocochlear system is suggestive of an electrotonic interaction between the
      bilateral olivocochlear neurons. The morphological background of the MOC pathway
      is not yet completely characterized. Therefore, we have labeled the bilateral
      cochlear nerves with different neuronal tracers in guinea pigs. In the
      anesthetized animals the cochlear nerves were exposed in the basal part of the
      modiolus and labeled simultaneously with different retrograde fluorescent
      tracers. By using confocal laser scanning microscope we could detect close
      appositions between the dendrites of the neurons of bilateral MOC. The distance
      between the neighboring profiles suggested close membrane appositions without
      interposing glial elements. These connections might serve as one of the
      underlying mechanisms of the binaural facilitation mediated by the olivocochlear
      system.

PMID- 21945540
TI  - Activation of glycogen synthase kinase-3 beta mediates beta-amyloid induced
      neuritic damage in Alzheimer's disease.
AB  - beta-Amyloid (Abeta) plaques in Alzheimer (AD) brains are surrounded by severe
      dendritic and axonal changes, including local spine loss, axonal swellings and
      distorted neurite trajectories. Whether and how plaques induce these neuropil
      abnormalities remains unknown. We tested the hypothesis that oligomeric
      assemblies of Abeta, seen in the periphery of plaques, mediate the
      neurodegenerative phenotype of AD by triggering activation of the enzyme GSK
      3beta, which in turn appears to inhibit a transcriptional program mediated by
      CREB. We detect increased activity of GSK-3beta after exposure to oligomeric
      Abeta in neurons in culture, in the brain of double transgenic APP/tau mice and
      in AD brains. Activation of GSK-3beta, even in the absence of Abeta, is
      sufficient to produce a phenocopy of Abeta-induced dendritic spine loss in
      neurons in culture, while pharmacological inhibition of GSK-3beta prevents spine
      loss and increases expression of CREB-target genes like BDNF. Of note, in
      transgenic mice GSK-3beta inhibition ameliorated plaque-related neuritic changes
      and increased CREB-mediated gene expression. Moreover, GSK-3beta inhibition
      robustly decreased the oligomeric Abeta load in the mouse brain. All these
      findings support the idea that GSK3beta is aberrantly activated by the presence
      of Abeta, and contributes, at least in part, to the neuronal anatomical
      derangement associated with Abeta plaques in AD brains and to Abeta pathology
      itself.

PMID- 21945542
TI  - The tropism of neurally differentiated bone marrow stromal cells towards C6
      glioma.
AB  - Recent studies have indicated that bone marrow stromal cells (BMSCs) have
      significant tropism towards glioma which makes them play an important role in
      carrying genes/drugs to inhibit the growth of glioma as cell vehicles. But BMSCs
      may differentiate into neural cells under entocranial environment and few
      researches support the idea that neurally differentiated bone marrow stromal
      cells (N-D-BMSCs) still hold the capacity of migrating to the tumor sites. The
      aim of our study was to investigate the tropism of N-D-BMSCs towards C6 glioma.
      In vitro migration assay was employed by transwell co-culture system and
      Student's t-test analysis indicated that N-D-BMSCs had the significant tropism
      towards C6 glioma-conditioned medium (GCM) (P<0.01). Furthermore, the vascular
      endothelial growth factor (VEGF) bioactivity of the C6 GCM was neutralized by the
      anti-rat VEGF antibody and our data suggested that the VEGF from C6 GCM hold
      chemoattraction for N-D-BMSCs and some other cytokines from the C6 GCM may be
      responsible for the chemoattraction for N-D-BMSCs. In vivo migration assay was
      carried out with cells transplantation and one way ANOVA analysis indicated that
      the tropism of N-D-BMSCs towards C6 glioma sites presented time variation (P
      value=2.9E-20). Moreover, multiple comparisons for the time variables with the
      Student's t-test and the results suggested that the migration capacity of N-D
      BMSCs towards C6 glioma sites reach the peak on the 7th day after
      transplantation. These results demonstrate that N-D-BMSCs as well as BMSCs have
      significant tropism towards C6 glioma.

PMID- 21945543
TI  - Visfatin induces neurite outgrowth in PC12 cells via ERK1/2 signaling pathway.
AB  - The angiogenic and inflammatory functions of visfatin and its effect on vascular
      cells, are fairly well known. However, its role within the nervous system remains
      largely unclear. To gain insight into this area, we studied the neuritogenic
      effect of visfatin on PC12 rat pheochromocytoma cells. We investigated whether
      visfatin gene expression, which is upregulated by hypoxia in cancer cells, is
      associated with neuritogenesis in PC12 cells. Using RT-PCR, Western blot
      analysis, ELISA, morphological observations, and immunostaining, we initially
      showed that CoCl(2), a hypoxic mimetic agent, upregulated visfatin gene
      expression along with neurite outgrowth in PC12 cells. We also showed that
      visfatin stimulated neurite outgrowth in PC12 cells. Moreover, in PC12 cells,
      visfatin evoked the activation of the extracellular signal-regulated kinase 1/2
      (ERK1/2), which is closely linked to neuritogenesis. Visfatin-induced outgrowth
      of neurites was prevented by inhibition of the ERK1/2 pathway. Taken together,
      our results demonstrate for the first time that visfatin induces neurite
      outgrowth in PC12 cells via the activation of an ERK-dependent pathway, and
      suggest that visfatin may exert various biological, physiological, and
      pathological functions in not only the vascular system but also the nervous
      system.

PMID- 21945544
TI  - Lamotrigine blocks repeated high-dose methamphetamine-induced behavioral
      sensitization to dizocilpine (MK-801), but not methamphetamine in rats.
AB  - We recently proposed a new psychostimulant animal model of the progressive
      pathophysiological changes of schizophrenia. Studies using that model produced a
      treatment strategy for preventing progression. Lamotrigine (LTG) blocks repeated
      high-dosage methamphetamine (METH)-induced initiation and expression of prepulse
      inhibition deficit and development of apoptosis in the medial prefrontal cortex
      (mPFC). Moreover, it inhibits METH-induced increases in extracellular glutamate
      levels in the mPFC (Nakato et al., 2011, Neurosci. Lett.). Abnormal behavior
      induced by METH or NMDA receptor antagonists is regarded as an animal model of
      schizophrenia. This study examined the effects of LTG on the development of
      behavioral sensitization to METH and cross-sensitization to dizocilpine (MK-801)
      by repeated administration of high-dose METH (2.5mg/kg, 10 times s.c.). Rats were
      injected repeatedly with LTG (30mg/kg) after 120min METH administration
      (2.5mg/kg). Repeated co-administration of LTG blocked the development of
      behavioral cross-sensitization to MK-801 (0.15mg/kg), but it did not prevent
      behavioral sensitization to METH (0.2mg/kg). The LTG-induced prevention of
      increased glutamate by high-dose METH might be related to the former finding.
      Combined results of our previous studies and this study suggest that LTG is
      useful to treat schizophrenia, especially at a critical point in its progression.

PMID- 21945545
TI  - Increase of galectin-3 expression in microglia by hyperthermia in delayed
      neuronal death of hippocampal CA1 following transient forebrain ischemia.
AB  - The ischemic damage in the hippocampal CA1 region following transient forebrain
      ischemia, delayed neuronal death, is a typical apoptotic response, but the
      underlying mechanisms are not fully understood. We have reported that mild
      hyperthermia (38  degrees C) accelerates DNA fragmentation of the gerbil CA1
      pyramidal neurons following transient forebrain ischemia. Recently, we reported
      that galectin-3, a beta-galactosidase-binding lectin, is spatio-temporally
      expressed only by activated microglial cells located within CA1 region following
      transient forebrain ischemia in gerbils. Furthermore, expression of galectin-3
      and Iba-1 (a specific microglial cell marker) are strongly reduced by hypothermia
      during ischemic insult. To further elucidate the effect of hyperthermia on the
      expression of galectin-3 by micloglia in delayed neuronal death, we examined
      immunohistochemical expression of galectin-3 and Iba-1, in situ terminal dUTP
      biotin nick end labeling of DNA fragmentation (for determination of cell death)
      and hematoxylin and eosin staining (for morphological observation). We observed
      that between 37  degrees C and 39  degrees C, there was a temperature-dependent
      enhancement of galectin-3 expression in microglial cells in the CA1 region
      following transient ischemia. Apoptotic DNA fragmentation, detected by TUNEL
      staining, was observed in CA1 region in normothermia. This TUNEL staining was
      enhanced by hyperthermia at 37.5  degrees C and 38  degrees C, but not at 39 
      degrees C. Ischemia-induced neuronal degeneration in CA1 region in gerbil
      hippocampus subjected to hyperthermia (37.5  degrees C, 38  degrees C and 39 
      degrees C) observed by HE staining is similar to that in normothermic gerbils.
      These findings imply that galectin-3 expression in microglia may influence the
      survival of CA1 pyramidal neurons in cases such as hyperthermia-related neuronal
      injury.

PMID- 21945546
TI  - Effects of RU486 in the expression of progesterone receptor isoforms in the
      hypothalamus and the preoptic area of the rat during postpartum estrus.
AB  - In several mammalian species females undergo postpartum estrus, a brief period of
      ovulation and sexual receptivity that in rats usually occurs during the first 24h
      following parturition. The maximal lordotic expression occurs at 12h after the
      initiation of parturition and depends on intracellular progesterone receptor
      (PR). We studied the regulation of PR expression by its antagonist, RU486 in the
      hypothalamus and the preoptic area of the rat during postpartum estrus by Western
      blot. Adult female rats were treated with RU486 (1.25 and 5mg) 3h after
      parturition, and Western blot was performed to assess the expression of PR-A and
      PR-B at 12h postpartum. RU486 (1.25 and 5mg) reduced the expression of PR-A (63%
      and 95%) and that of PR-B (75% and 99%), respectively in the preoptic area
      whereas it had no effects in the hypothalamus. These results suggest a
      differential regulation of PR expression in the rat brain during postpartum
      estrus.

PMID- 21945547
TI  - Recognition of stimulus-evoked neuronal optical response by identifying chaos
      levels of near-infrared spectroscopy time series.
AB  - Near-infrared spectroscopy (NIRS) can detect two different kinds of signals from
      the human brain: the hemodynamic response (slow) and the neuronal response
      (fast). This paper explores a nonlinear aspect in the tactile-stimulus-evoked
      neuronal optical response over a NIRS time series (light intensity variation).
      The existence of the fast optical responses (FORs) over the time series recorded
      in stimulus sessions is confirmed by event-related averaging. The chaos levels of
      the NIRS time series recorded both in stimulus and in rest sessions are then
      identified according to the estimated largest Lyapunov exponent. The obtained
      results ascertain that stimulus-evoked neuronal optical responses can be detected
      in the somatosensory cortex using continuous-wave NIRS equipment. Further, the
      results strongly suggest that the chaos level can be used to recognize the FORs
      in NIRS time series and, thereby, the state of the pertinent brain activity.

PMID- 21945548
TI  - Awareness of cognitive impairment in schizophrenia and its relationship to
      insight into illness.
AB  - BACKGROUND: Patients with schizophrenia have been found to show unawareness of
      cognitive impairment. However, its frequency and its relationship to lack of
      insight into illness are uncertain. METHOD: Forty-two patients with chronic
      schizophrenia were given tests of executive function and memory. Awareness of
      cognitive impairment was measured by means of discrepancy scores--differences
      between patient and psychologist ratings of memory and frontal/executive failures
      in daily life. Insight into illness was assessed using the Scale to Assess
      Unawareness of Mental Disorder (SUMD). RESULTS: A majority of the patients were
      found to underestimate their cognitive impairment; however, some overestimated
      it. Unawareness of cognitive impairment and lack of clinical insight loaded on
      different factors in a factor analysis, but these two factors were themselves
      correlated. CONCLUSIONS: The findings suggest that both unawareness and
      overestimation of cognitive impairment characterise patients with schizophrenia,
      although the former is more common. Awareness of cognitive impairment occurs
      independently of insight into illness at the clinical level, although the two
      phenomena may be linked at a deeper level.

PMID- 21945550
TI  - Anaerobic digestion of organic fraction of municipal solid waste combining two
      pretreatment modalities, high temperature microwave and hydrogen peroxide.
AB  - In order to enhance anaerobic digestion (AD) of the organic fraction of municipal
      solid waste (OFMSW), pretreatment combining two modalities, microwave (MW)
      heating in presence or absence of hydrogen peroxide (H(2)O(2)) were investigated.
      The main pretreatment variables affecting the characteristics of the OFMSW were
      temperature (T) via MW irradiation and supplemental water additions of 20% and
      30% (SWA20 and SW30). Subsequently, the focus of this study was to evaluate
      mesophilic batch AD performance in terms of biogas production, as well as changes
      in the characteristics of the OFMSW post digestion. A high MW induced temperature
      range (115-175 degrees C) was applied, using sealed vessels and a bench scale MW
      unit equipped with temperature and pressure controls. Biochemical methane
      potential (BMP) tests were conducted on the whole OFMSW as well as the liquid
      fractions. The whole OFMSW pretreated at 115 degrees C and 145 degrees C showed 4
      7% improvement in biogas production over untreated OFMSW (control). When
      pretreated at 175 degrees C, biogas production decreased due to formation of
      refractory compounds, inhibiting the digestion. For the liquid fraction of OFMSW,
      the effect of pretreatment on the cumulative biogas production (CBP) was more
      pronounced for SWA20 at 145 degrees C, with a 26% increase in biogas production
      after 8days of digestion, compared to the control. When considering the increased
      substrate availability in the liquid fraction after MW pretreatment, a 78%
      improvement in biogas production vs. the control was achieved. Combining MW and
      H(2)O(2) modalities did not have a positive impact on OFMSW stabilization and
      enhanced biogas production. In general, all samples pretreated with H(2)O(2)
      displayed a long lag phase and the CBP was usually lower than MW irradiated only
      samples. First order rate constant was calculated.

PMID- 21945549
TI  - The heritability of the skin conductance orienting response: a longitudinal twin
      study.
AB  - The orienting response is a widely used experimental paradigm that reflects the
      association between electrodermal activity and psychological processes. The
      present study examined the genetic and environmental etiology of skin conductance
      orienting response (SCOR) magnitude in a sample of twins assessed at ages 9-10,
      11-13 and 14-16 years. Structural equation modeling at each visit showed that
      genetic influences explained 56%, 83%, and 48% of the total variance in SCOR at
      visits 1, 2, and 3, respectively, with the remaining variance explained by non
      shared environmental factors. SCOR was moderately stable across ages, with
      phenotypic correlations between time points ranging from .35 to .45. A common
      genetic factor explained 36%, 45% and 49% of the variance in SCOR magnitude
      across development. Additional age-specific genetic effects were found at ages 9
      10 and 11-13 years, explaining 18% and 35% of the variance, respectively. The
      genetic correlations among the three time points were high, ranging from .55 to
      .73, indicating a substantial continuity in genetic influences from ages 9 to 16.
      These findings suggest that genetic factors are important influences in SCOR
      magnitude during late childhood and adolescence.

PMID- 21945551
TI  - The role of cytoreductive surgery for newly diagnosed advanced-stage uterine
      carcinosarcoma.
AB  - OBJECTIVES: Uterine carcinosarcoma (CS) is a rare but aggressive malignancy
      frequently associated with extrauterine metastasis at the time of diagnosis. The
      objective of this study was to assess the role of cytoreductive surgery in
      patients with stage IIIC-IVB uterine CS. METHODS: We conducted a retrospective
      review of all patients with uterine CS treated at our institution from 1990 to
      2009. Clinicopathologic factors, surgical procedures, adjuvant therapy, and
      survival outcomes were collected for all patients. Progression-free survival
      (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method.
      Factors predictive of survival outcomes were compared using the log-rank test and
      Cox regression analysis. RESULTS: An analysis of 44 patients was performed (stage
      IIIC, n=14; stage IVB, n=30). Complete gross resection was achieved in 57% of
      patients. PFS and OS for the entire cohort were 8.6 months and 18.5 months,
      respectively. Complete gross resection was associated with a median OS of 52.3
      months versus 8.6 months in patients with gross residual disease (P<0.0001).
      Stage IIIC disease was associated with a median OS of 52.3 months versus 17.5
      months for patients with stage IVB disease. In patients who received adjuvant
      therapy, OS was 30.1 months versus 4.7 months in patients who did not receive
      adjuvant therapy (P<0.001). On multivariate analysis, only complete gross
      resection and the ability to receive adjuvant therapy were independently
      associated with OS. CONCLUSIONS: Cytoreductive surgery, with a goal of achieving
      a complete gross resection, is associated with an improvement in OS among
      patients with advanced uterine CS.

PMID- 21945552
TI  - A high response rate to liposomal doxorubicin is seen among women with BRCA
      mutations treated for recurrent epithelial ovarian cancer.
AB  - OBJECTIVE: Ten percent of ovarian cancer is attributed to hereditary syndromes,
      most commonly to mutations in the BRCA1 or BRCA2 genes. These cancers are
      characterized by a prolonged sensitivity to platinum agents in spite of
      presentation at advanced stages. We hypothesized that women with BRCA-associated
      ovarian cancer would also show a high response rate to pegylated liposomal
      doxorubicin (Doxil). METHODS: A retrospective cohort study was conducted to
      compare the response rate, progression-free, and overall survival among women
      with BRCA-associated or sporadic ovarian cancer who were treated with Doxil.
      RESULTS: A response to Doxil was seen in 13 of 23 patients with BRCA mutations
      (56.5%; 3 by RECIST criteria and 10 by CA125 levels) compared with only 8 of 41
      women with non-hereditary cancers (19.5%; 2 by RECIST criteria and 6 by CA125
      levels; p=0.004). This was associated with an improved progression-free and
      overall survival as measured from the time of Doxil administration. Notably,
      platinum sensitivity did not directly correlate with a response to Doxil.
      CONCLUSIONS: Women with BRCA-associated ovarian tumors demonstrate a greater
      sensitivity to cytotoxic therapy with Doxil than has previously been reported in
      unselected cases.

PMID- 21945553
TI  - Sentinel lymph node biopsy in endometrial cancer: meta-analysis of 26 studies.
AB  - OBJECTIVE: The validity of the sentinel lymph node (SLN) procedure for the
      assessment of nodal status in patients with endometrial cancer is unclear. We
      aimed to assess the diagnostic performance of this procedure. METHODS: We
      searched the PubMed and Embase databases for studies published before June 1,
      2011. Eligible studies had a sample size of at least 10 patients, and reported
      the detection rate and/or sensitivity of the SLN biopsy. RESULTS: We identified
      26 eligible studies, which included 1101 SLN procedures. The overall weighted
      mean number of harvested SLNs was 2.6. The detection rate and the sensitivity
      were 78% (95% confidence interval [CI]=73%-84%) and 93% (95% CI=87%-100%),
      respectively. Significant between-study heterogeneity was observed in the
      analysis of the detection rate (I-squared statistic, 80%). The use of
      pericervical injection was correlated with the increase of the detection rate
      (P=0.031). The hysteroscopic injection technique was associated with the decrease
      of the detection rate (P=0.045) and the subserosal injection technique was
      associated with the decrease of the sensitivity (P=0.049), if they were not
      combined with other injection techniques. For the detection rate, significant
      small-study effects were noted (P<0.001). CONCLUSIONS: Although SLN biopsy has
      shown good diagnostic performance in endometrial cancer, such performance should
      be interpreted with caution because of significant small study effects. Current
      evidence is not yet sufficient to establish the true performance of SLN biopsy in
      endometrial cancer.

PMID- 21945554
TI  - Changing trend in the patterns of pretreatment diagnostic assessment for patients
      with cervical cancer in Japan.
AB  - OBJECTIVE: Cancer staging systems should be responsive to the development of
      diagnostic tools. The International Federation of Gynecology and Obstetrics
      (FIGO) cervical cancer guidelines were modified in 2009 regarding the
      pretreatment assessment. We report the recent Japanese patterns of pretreatment
      workup for cervical cancer. METHODS: The Japanese Patterns of Care Study (PCS)
      working group analyzed the pretreatment diagnostic assessment data of 609
      patients with cervical cancer treated with definitive radiotherapy in the two
      survey periods (1999-2001, 324; 2003-2005, 285) in Japan. Sixty-one of 640
      institutions were selected for this survey using a stratified two-staged cluster
      sampling method. RESULTS: The use of optional examinations in the latest FIGO
      guidelines such as intravenous urography, cystoscopy, and proctoscopy was
      gradually decreasing. Surgical staging was rarely performed in either survey
      period. Computed tomography (CT) and magnetic resonance imaging (MRI) were widely
      used, and MRI has become increasingly prevalent even between the two survey
      periods. Primary lesion size and pelvic lymph node status was evaluated by CT/MRI
      for most patients in both surveys. CONCLUSIONS: The use of CT/MRI that is
      encouraged in the latest FIGO staging guidelines already replaced intravenous
      urography, cystoscopy, and proctoscopy in Japan. Japanese patients received the
      potential benefit of CT/MRI because prognostic factors such as primary lesion
      size and pelvic lymph node status were evaluated by these modalities. The use of
      cystoscopy and proctoscopy should be continuously monitored in the future PCS
      survey because only CT/MRI could lead to the stage migration for patients on
      suspicion of bladder/rectum involvement on CT/MRI.

PMID- 21945556
TI  - Are we loving 'em to death?

PMID- 21945555
TI  - Novel structural insights into rotavirus recognition of ganglioside glycan
      receptors.
AB  - Rotaviruses ubiquitously infect children under the age of 5, being responsible
      for more than half a million diarrhoeal deaths each year worldwide. Host cell
      oligosaccharides containing sialic acid(s) are critical for attachment by
      rotaviruses. However, to date, no detailed three-dimensional atomic model showing
      the exact rotavirus interactions with these glycoconjugate receptors has been
      reported. Here, we present the first crystallographic structures of the rotavirus
      carbohydrate-recognizing protein VP8* in complex with ganglioside G(M3) glycans.
      In combination with assessment of the inhibition of rotavirus infectivity by N
      acetyl and N-glycolyl forms of this ganglioside, our results reveal key details
      of rotavirus-ganglioside G(M3) glycan recognition. In addition, they show a
      direct correlation between the carbohydrate specificities exhibited by VP8* from
      porcine and by monkey rotaviruses and the respective infectious virus particles.
      These novel results also indicate the potential binding interactions of rotavirus
      VP8* with other sialic acid-containing gangliosides.

PMID- 21945557
TI  - Antibiotic resistance of bacteria isolated from shrimp hatcheries and cultural
      ponds on Donghai Island, China.
AB  - The resistance of bacteria to 12 different antibiotics was investigated in shrimp
      farms on Donghai Island, China. Antibiotic-resistant bacteria were found to be
      widespread in shrimp farms, indicating a high environmental risk. Further,
      significant differences were found in bacterial strains among farms (ANOVA,
      p<0.05), showing resistance to antibiotics such as ampicillin, trimethoprim,
      compound sinomi, tetracycline, chloramphenicol and cefazolin. No significant
      differences in antibiotic resistance were found among 6 hatcheries evaluated in
      this study (ANOVA, p>0.05), between exalted and traditional shrimp ponds (ANOVA,
      p>0.05), and between cultural ponds and corresponding control water source sites
      (T-test, p>0.05). In cultural ponds, no significant difference in bacterial
      resistance to antibiotics was found between water and sediment (T-test, p>0.05),
      and antibiotic resistance of bacteria from water showed a significant positive
      correlation with that from sediment (p<0.05). Therefore, our study indicates that
      bacterial multiple antibiotic resistance (MAR) is more widespread in shrimp
      hatcheries than ponds.

PMID- 21945558
TI  - Tributyltin in blood of marine fish collected from a coastal area of northern
      Kyushu, Japan.
AB  - We investigated levels of the pollutant tributyltin (TBT) in blood of
      pufferfishes (six species), Japanese sea perch, red sea bream, Japanese common
      goby, Japanese flounder, rockfish, conger eel, and sea mullet collected off the
      coast of northern Kyushu, Japan. We found considerable levels of TBT (1.4-190
      ng/mL) accumulated in the blood of these fish. Blood TBT concentrations were 1.3
      22.5 times liver concentrations and 4.9-78 times muscle concentrations, except in
      conger eel and mullet. We detected TBT (16-111 ng/mL-blood) in the plasma of the
      fine-patterned puffer (Takifugupoecilonotus) year-round, without any apparent
      seasonal trend. These results suggest that fish inhabiting coastal areas of
      Kyushu, Japan, continue to be contaminated with TBT.

PMID- 21945559
TI  - Long-term coexistence of non-indigenous species in aquaculture facilities.
AB  - Non-indigenous species (NIS) are a growing problem globally and, in the sea,
      aquaculture activities are critical vectors for their introduction. Aquaculture
      introduces NIS, intentionally or unintentionally, and can provide substratum for
      the establishment of other NIS. Little is known about the co-occurrence of NIS
      over long periods and we document the coexistence over decades of a farmed NIS (a
      mussel) with an accidently introduced species (an ascidian). Both are widespread
      and cause serious fouling problems worldwide. We found partial habitat
      segregation across depth and the position of rafts within the studied farm, which
      suggests competitive exclusion of the mussel in dark, sheltered areas and
      physiological exclusion of the ascidian elsewhere. Both species exhibit massive
      self-recruitment, with negative effects on the industry, but critically the
      introduction of NIS through aquaculture facilities also has strong detrimental
      effects on the natural environment.

PMID- 21945560
TI  - Phytoplankton distribution and productivity in a highly turbid, tropical coastal
      system (Bach Dang Estuary, Vietnam).
AB  - Phytoplankton diversity, primary and bacterial production, nutrients and metallic
      contaminants were measured during the wet season (July) and dry season (March) in
      the Bach Dang Estuary, a sub-estuary of the Red River system, Northern Vietnam.
      Using canonical correspondence analysis we show that phytoplankton community
      structure is potentially influenced by both organometallic species (Hg and Sn)
      and inorganic metal (Hg) concentrations. During March, dissolved methylmercury
      and inorganic mercury were important factors for determining phytoplankton
      community composition at most of the stations. In contrast, during July, low
      salinity phytoplankton community composition was associated with particulate
      methylmercury concentrations, whereas phytoplankton community composition in the
      higher salinity stations was more related to dissolved inorganic mercury and
      dissolved mono and tributyltin concentrations. These results highlight the
      importance of taking into account factors other than light and nutrients, such as
      eco-toxic heavy metals, in understanding phytoplankton diversity and activity in
      estuarine ecosystems.

PMID- 21945561
TI  - Intracerebroventricular administration of inosine is anticonvulsant against
      quinolinic acid-induced seizures in mice: an effect independent of benzodiazepine
      and adenosine receptors.
AB  - Inosine (INO) has an anticonvulsant effect against seizures induced by
      antagonists of GABAergic system. Quinolinic acid (QA) is an agonist NMDA
      receptors implicated in the neurobiology of seizures. In the present study, we
      investigated the anticonvulsant effect of intracerebroventricular (i.c.v.) INO
      administration against QA-induced seizures in adult mice. We also investigated
      whether the benzodiazepines (BZ) or adenosine (ADO) receptors were involved in
      the INO effects. Animals were pretreated with an i.c.v. injection of either
      vehicle or INO before an i.c.v. administration of 4 MUl QA (36.8 nmol). All
      animals pretreated with vehicle followed by QA presented seizures. INO protected
      against QA-induced seizures in a time and dose dependent manner (up to 60% at 400
      nmol, 5 min before QA injection). Diazepam (DZ) and ADO (i.c.v.) also exhibited
      anticonvulsant effect against QA induced seizures. Additionally, i.p.
      administration of either flumazenil, a BZ receptor antagonist, or caffeine, an
      ADO receptor antagonist, did not change the anticonvulsant potency of INO i.c.v.
      injection, but completely abolished the DZ and ADO anticonvulsant effects,
      respectively. In conclusion, this study demonstrated that INO exert
      anticonvulsant effect against hyperactivity of the glutamatergic system
      independently of BZ or ADO receptors activation.

PMID- 21945562
TI  - Reproducibility of multiple repeated oral glucose tolerance tests.
AB  - We assessed the oral glucose tolerance test's (OGTT) ability to produce
      consistent results for estimating insulin sensitivity over four consecutive days.
      Individual coefficients of variation for OGIS and Stumvoll-ISI were 7.8% and
      14.4% with no statistically significant difference between days. Thereby,
      indicating repeated OGTT's are reliable for estimating insulin sensitivity.

PMID- 21945563
TI  - Fluorescent probe partitioning in GUVs of binary phospholipid mixtures:
      implications for interpreting phase behavior.
AB  - The phase behavior of membrane lipids is known to influence the organization and
      function of many integral proteins. Giant unilamellar vesicles (GUVs) provide a
      very useful model system in which to examine the details of lipid phase
      separation using fluorescence imaging. The visualization of domains in GUVs of
      binary and ternary lipid mixtures requires fluorescent probes with partitioning
      preference for one of the phases present. To avoid possible pitfalls when
      interpreting the phase behavior of these lipid mixtures, sufficiently thorough
      characterization of the fluorescent probes used in these studies is needed. It is
      now evident that fluorescent probes display different partitioning preferences
      between lipid phases, depending on the specific lipid host system. Here, we
      demonstrate the benefit of using a panel of fluorescent probes and confocal
      fluorescence microscopy to examine phase separation in GUVs of binary mixtures of
      1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)/1,2-dipalmitoyl-sn-glycero-3
      phosphocholine (DPPC). Patch and fibril gel phase domains were found to co-exist
      with liquid disordered (l(d)) domains on the surface of GUVs composed of 40:60
      mol% DOPC/DPPC, over a wide range of temperatures (14-25 degrees C). The
      fluorescent lipid, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-(7-nitro-2
      1,3-benzoxadiazol-4-yl (NBD-DPPE), proved to be the most effective probe for
      visualization of fibril domains. In the presence of Lissamine(TM) rhodamine B 1,2
      dihexadecanoyl-sn-glycero-3-phosphoethanolamine (Rh-DPPE) we were unable to
      detect fibril domains. This fluorophore also affected the partitioning behavior
      of other fluorescent probes. Overall, we show that the selection of different
      fluorescent probes as lipid phase reporters can result in very different
      interpretation of the phase behavior of DOPC/DPPC mixtures.

PMID- 21945564
TI  - First insights on the validity of the concept of Cancer Literacy: a test in a
      sample of Ticino (Switzerland) residents.
AB  - OBJECTIVE: To develop a measure of Cancer Literacy and have a first insight into
      the validity of the concept. METHODS: A measure of Cancer Literacy was developed
      and administered to a sample of Ticino (Switzerland) residents (N=639). Internal
      consistency, test-retest reliability and construct validity of the measure were
      assessed. RESULTS: The Cancer Literacy Score (CLS) showed acceptable internal
      consistency and 4-week test-retest reliability. Independent-samples t-tests and
      one-way ANOVAs confirmed that women, Swiss citizens, people with higher
      educational levels, people with a medical qualification, and people who had
      played an active role in the cancer experience of a family member or a friend
      presented significantly higher CLS. Correlational analyses indicated a more
      positive attitude towards screening participation and engagement in health
      promoting behaviours in people with higher levels of Cancer Literacy. CONCLUSIONS
      AND PRACTICE IMPLICATIONS: The Cancer Literacy scale provides us with evidence of
      the validity of our conceptual attempt to go in the direction of a context- and
      content-specific concept of health literacy. Despite some limitations and the
      need for further refinement before it can be applied on a larger scale, the scale
      already offers Ticino researchers and public health workers a comprehensive
      measure of cancer knowledge.

PMID- 21945566
TI  - Determining the effect of the incorporation of unnatural amino acids into
      antimicrobial peptides on the interactions with zwitterionic and anionic membrane
      model systems.
AB  - Circular Dichroism (CD), isothermal calorimetry (ITC) and calcein fluorescence
      leakage experiments were conducted to provide insight into the mechanisms of
      binding of a series of antimicrobial peptides containing unnatural amino acids
      (Ac-XF-Tic-Oic-XK-Tic-Oic-XF-Tic-Oic-XK-Tic-KKKK-CONH(2)) to zwitterionic and
      anionic micelles, SUVs and LUVs; where X (Spacer# 1) is either Gly, beta-Ala,
      Gaba or 6-aminohexanoic acid. It is the intent of this investigation to correlate
      these interactions with the observed potency and selectivity against several
      different strains of bacteria. The CD spectra of these compounds in the presence
      of zwitterionic DPC micelles and anionic SDS micelles are very different
      indicating that these compounds adopt different conformations on binding to the
      surface of anionic and zwitterionic membrane models. These compounds also
      exhibited very different CD spectra in the presence of zwitterionic POPC and
      anionic mixed 4:1 POPC/POPG SUVs and LUVs, indicating the formation of different
      conformations on interaction with the two membrane types. This observation is
      also supported by ITC and calcein leakage data. ITC data suggested these peptides
      interact primarily with the surface of zwitterionic LUVs and was further
      supported by fluorescence experiments where the interactions do not appear to be
      concentration dependent. In the presence of anionic membranes, the interactions
      appear more complex and the calorimetric and fluorescence data both imply pore
      formation is dependent on peptide concentration. Furthermore, evidence suggests
      that as the length of Spacer# 1 increases the mechanism of pore formation also
      changes. Based on the observed differences in the mechanisms of interactions with
      zwitterionic and anionic LUVs these AMPs are potential candidates for further
      drug development.

PMID- 21945567
TI  - Fluid movement and joint capsule strains due to flexion in rabbit knees.
AB  - Diarthrodial joints are freely moveable joints containing synovial fluid (SF)
      within a connective tissue joint capsule that allows for low-friction and low
      wear articulation of the cartilaginous ends of long bones. Biomechanical cues
      from joint articulation regulate synoviocyte and cartilage biology via joint
      capsule strain, in turn altering the composition of SF. Joint flexion is
      clinically associated with pain in knees with arthritis and effusion, with the
      nociception possibly originating from joint capsule strain. The hypothesis of
      this study was that knee fluid volume distribution and joint capsule strain are
      altered with passive flexion in the rabbit model. The aims were to (a) determine
      the volume distribution of fluid in the joint at different total volumes and with
      flexion of rabbit knees ex vivo, (b) correlate the volume distribution for the ex
      vivo model to in vivo data, and (c) determine the strains at different locations
      in the joint capsule with flexion. During knee flexion, ~20% of anteriorly
      located joint fluid moved posteriorly, correlating well with the fluid motion
      observed in in vivo joints. Planar joint capsule principal strains were ~100%
      (tension) in the proximal-distal direction and ~-40% (shortening) in the
      circumferential direction, relative to the femur axis and 30 degrees  strain
      state. The joint capsule strains with flexion are consistent with the mechanics
      of the tendons and ligaments from which the capsule tissue is derived. The
      movement and mixing of SF volume with flexion determine the mechanical and
      biological fluid environment within the knee joint. Joint fluid movement and
      capsular strains affect synovial cell biology and likely modulate trans-synovial
      transport.

PMID- 21945565
TI  - Membrane-active host defense peptides--challenges and perspectives for the
      development of novel anticancer drugs.
AB  - Although much progress has been achieved in the development of cancer therapies
      in recent decades, problems continue to arise particularly with respect to
      chemotherapy due to resistance to and low specificity of currently available
      drugs. Host defense peptides as effector molecules of innate immunity represent a
      novel strategy for the development of alternative anticancer drug molecules.
      These cationic amphipathic peptides are able to discriminate between neoplastic
      and non-neoplastic cells interacting specifically with negatively charged
      membrane components such as phosphatidylserine (PS), sialic acid or heparan
      sulfate, which differ between cancer and non-cancer cells. Furthermore, an
      increased number of microvilli has been found on cancer cells leading to an
      increase in cell surface area, which may in turn enhance their susceptibility to
      anticancer peptides. Thus, part of this review will be devoted to the differences
      in membrane composition of non-cancer and cancer cells with a focus on the
      exposure of PS on the outer membrane. Normally, surface exposed PS triggers
      apoptosis, which can however be circumvented by cancer cells by various means.
      Host defense peptides, which selectively target differences between cancer and
      non-cancer cell membranes, have excellent tumor tissue penetration and can thus
      reach the site of both primary tumor and distant metastasis. Since these
      molecules kill their target cells rapidly and mainly by perturbing the integrity
      of the plasma membrane, resistance is less likely to occur. Hence, a chapter will
      also describe studies related to the molecular mechanisms of membrane damage as
      well as alternative non-membrane related mechanisms. In vivo studies have
      demonstrated that host defense peptides display anticancer activity against a
      number of cancers such as e.g. leukemia, prostate, ascite and ovarian tumors, yet
      so far none of these peptides has made it on the market. Nevertheless,
      optimization of host defense peptides using various strategies to enhance further
      selectivity and serum stability is expected to yield novel anticancer drugs with
      improved properties in respect of cancer cell toxicity as well as reduced
      development of drug resistance.

PMID- 21945568
TI  - Paretic muscle atrophy and non-contractile tissue content in individual muscles
      of the post-stroke lower extremity.
AB  - Muscle atrophy is one of many factors contributing to post-stroke hemiparetic
      weakness. Since muscle force is a function of muscle size, the amount of muscle
      atrophy an individual muscle undergoes has implications for its overall force
      generating capability post-stroke. In this study, post-stroke atrophy was
      determined bilaterally in fifteen leg muscles with volumes quantified using
      magnetic resonance imaging (MRI). All muscle volumes were adjusted to exclude non
      contractile tissue content, and muscle atrophy was quantified by comparing the
      volumes between paretic and non-paretic sides. Non-contractile tissue or
      intramuscular fat was calculated by determining the amount of tissue excluded
      from the muscle volume measurement. With the exception of the gracilis, all
      individual paretic muscles examined had smaller volumes in the non-paretic side.
      The average decrease in volume for these paretic muscles was 23%. The gracilis
      volume, on the other hand, was approximately 11% larger on the paretic side. The
      amount of non-contractile tissue was higher in all paretic muscles except the
      gracilis, where no difference was observed between sides. To compensate for
      paretic plantar flexor weakness, one idea might be that use of the paretic
      gracilis actually causes the muscle to increase in size and not develop
      intramuscular fat. By eliminating non-contractile tissue from our volume
      calculations, we have presented volume data that more appropriately represents
      force-generating muscle tissue. Non-uniform muscle atrophy was observed across
      muscles and may provide important clues when assessing the effect of muscle
      atrophy on post-stroke gait.

PMID- 21945569
TI  - Strains at the myotendinous junction predicted by a micromechanical model.
AB  - The goal of this work was to create a finite element micromechanical model of the
      myotendinous junction (MTJ) to examine how the structure and mechanics of the MTJ
      affect the local micro-scale strains experienced by muscle fibers. We validated
      the model through comparisons with histological longitudinal sections of muscles
      fixed in slack and stretched positions. The model predicted deformations of the A
      bands within the fiber near the MTJ that were similar to those measured from the
      histological sections. We then used the model to predict the dependence of local
      fiber strains on activation and the mechanical properties of the endomysium. The
      model predicted that peak micro-scale strains increase with activation and as the
      compliance of the endomysium decreases. Analysis of the models revealed that, in
      passive stretch, local fiber strains are governed by the difference of the
      mechanical properties between the fibers and the endomysium. In active stretch,
      strain distributions are governed by the difference in cross-sectional area along
      the length of the tapered region of the fiber near the MTJ. The endomysium
      provides passive resistance that balances the active forces and prevents the
      tapered region of the fiber from undergoing excessive strain. These model
      predictions lead to the following hypotheses: (i) the increased likelihood of
      injury during active lengthening of muscle fibers may be due to the increase in
      peak strain with activation and (ii) endomysium may play a role in protecting
      fibers from injury by reducing the strains within the fiber at the MTJ.

PMID- 21945570
TI  - Shear strength and toughness of trabecular bone are more sensitive to density
      than damage.
AB  - Microdamage occurs in trabecular bone under normal loading, which impairs the
      mechanical properties. Architectural degradation associated with osteoporosis
      increases damage susceptibility, resulting in a cumulative negative effect on the
      mechanical properties. Treatments for osteoporosis could be targeted toward
      increased bone mineral density, improved architecture, or repair and prevention
      of microdamage. Delineating the relative roles of damage and architectural
      degradation on trabecular bone strength will provide insight into the most
      beneficial targets. In this study, damage was induced in bovine trabecular bone
      samples by axial compression, and the effects on the mechanical properties in
      shear were assessed. The damaged shear modulus, shear yield stress, ultimate
      shear stress, and energy to failure all depended on induced damage and decreased
      as the architecture became more rod-like. The changes in ultimate shear strength
      and toughness were proportional to the decrease in shear modulus, consistent with
      an effective decrease in the cross-section of trabeculae based on cellular solid
      analysis. For typical ranges of bone volume fraction in human bone, the strength
      and toughness were much more sensitive to decreased volume fraction than to
      induced mechanical damage. While ultimately repairing or avoiding damage to the
      bone structure and increasing bone density both improve mechanical properties,
      increasing bone density is the more important contributor to bone strength.

PMID- 21945572
TI  - Efficacy of auto-crosslinked hyaluronan gel for adhesion prevention in
      laparoscopy and hysteroscopy: a systematic review and meta-analysis of randomized
      controlled trials.
AB  - Prevention of postoperative adhesions is a clinical need. We undertook a
      systematic review to explore the available clinical evidence of the efficacy of
      auto-crosslinked hyaluronan gel for postoperative adhesion prevention following
      endoscopic gynecological surgery. An electronic database search of MEDLINE,
      Cochrane Database of Systematic Reviews and EMBASE, and a comprehensive hand
      search of reference lists of published and review articles were performed. No
      language restrictions were applied. Randomized controlled trials (RCTs) on the
      use of auto-crosslinked hyaluronan gel for the prevention of postoperative
      adhesions in gynecological surgery were included in the meta-analysis if they
      reported outcomes as evaluated at a blind second-look assessment. Three authors
      independently selected studies and extracted data on study characteristics,
      quality and accuracy. The Jadad scoring system was used for validity assessment.
      Meta-analysis was performed following the Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The outcome was the
      incidence of postoperative adhesions based on a binary response (present or not
      present). Only five RCTs were eligible for inclusion in the meta-analysis. The
      incidence of postoperative adhesions in patients who received auto-crosslinked
      hyaluronan gel was significantly lower than in patients who underwent standard
      surgery only. The gel prevented both intraperitoneal adhesions after laparoscopic
      myomectomy (OR 0.248, 95% CI 0.098, 0.628) and intrauterine adhesions after
      hysteroscopic surgery (OR 0.408, 95% CI 0.217, 0.766). Further RCTs are needed to
      assess the efficacy of auto-crosslinked hyaluronan gel in women undergoing
      different laparoscopic intra-abdominal surgical procedures.

PMID- 21945573
TI  - Tinzaparin use in pregnancy: an international, retrospective study of the safety
      and efficacy profile.
AB  - OBJECTIVES: This study audited pregnancies where the mother received tinzaparin
      (at any stage before delivery), with a primary objective of determining the
      maternal safety of this low molecular weight heparin when administered as
      treatment and/or prophylaxis; the secondary objective was to audit fetal and
      neonatal safety in this cohort. Efficacy outcomes were also recorded. STUDY
      DESIGN: The audit period was 1996-2009; consecutive, retrospective pregnancy
      records at participating hospitals were reviewed. For those records documenting
      tinzaparin use and pregnancy outcome, information was extracted into a
      standardised case report form; these were reviewed for adverse events, which were
      submitted for adjudication by independent experts in obstetric medicine and
      haematology. Endpoints were presented using descriptive statistics for all
      pregnancies, and by reason for tinzaparin use (treatment of venous
      thromboembolism [VTE] and prophylaxis). RESULTS: There were 28 participating
      hospital centres in eight countries (Belgium, Canada, Denmark, Ireland,
      Netherlands, Sweden, Spain and the UK). Data were collected from 1267 pregnancies
      (1120 women; 1303 fetuses); in 254 pregnancies the women received tinzaparin as
      treatment (median dose 13,000 international units [IU]/day, range 3500
      23,100IU/day; median duration 72 days; 94.1% once-daily), and in 1013 pregnancies
      the women received tinzaparin for prophylaxis (median dose 4500IU/day, range 2500
      21,811IU/day, median duration 183 days, 94.6% once-daily). There were 871 (70.2%)
      vaginal deliveries (78 assisted) and 369 (29.8%) caesarean sections (27 delivery
      data missing). Overall, 495 (39.3%) women had neuraxial anaesthesia; however,
      there were no reported associated haematomas. There were no maternal deaths. Of
      pregnancies with available data (1060), 86.9% had blood loss <=500mL, 11.0% of
      >500 to <=1000mL, 0.9% >1000 to <=1500mL and 1.1% >1500mL. There were 1245
      (95.5%) live births, 15 (1.2%) stillbirths, 40 (3.1%) miscarriages and 3 (0.2%)
      terminations. Six (0.5%) neonatal deaths occurred (five at <27 weeks, one
      Ebstein's anomaly). No neonatal haemorrhages occurred. Adjudicated safety
      outcomes included 125 (9.9%) 'any bleeding' cases considered related to
      tinzaparin; 16 (1.3%) of these required medical intervention. In the treatment
      group, five (2%) recurrent VTEs were reported and 10 (1%) occurred in the
      prophylaxis group. CONCLUSIONS: These data provide reassuring maternal and fetal
      outcome information in pregnancies exposed to tinzaparin.

PMID- 21945574
TI  - Acute ischemia in upper limb secondary to myxoma.

PMID- 21945571
TI  - The proinflammatory cytokine GM-CSF downregulates fetal hemoglobin expression by
      attenuating the cAMP-dependent pathway in sickle cell disease.
AB  - Although reduction in leukocyte counts following hydroxyurea therapy in sickle
      cell disease (SCD) predicts fetal hemoglobin (HbF) response, the underlying
      mechanism remains unknown. We previously reported that leukocyte counts are
      regulated by granulocyte-macrophage colony-stimulating factor (GM-CSF) in SCD
      patients. Here we examined the roles of GM-CSF in the regulation of HbF
      expression in SCD. Upon the analysis of retrospective data in 372 patients, HbF
      levels were inversely correlated with leukocyte counts and GM-CSF levels in SCD
      patients without hydroxyurea therapy, while HbF increments after hydroxyurea
      therapy correlated with a reduction in leukocyte counts, suggesting a negative
      effect of GM-CSF on HbF expression. Consistently, in vitro studies using primary
      erythroblasts showed that the addition of GM-CSF to erythroid cells decreased HbF
      expression. We next examined the intracellular signaling pathway through which GM
      CSF reduced HbF expression. Treatment of erythroid cells with GM-CSF resulted in
      the reduction of intracellular cAMP levels and abrogated phosphorylation of cAMP
      response-element-binding-protein, suggesting attenuation of the cAMP-dependent
      pathway, while the phosphorylation levels of mitogen-activated protein kinases
      were not affected. This is compatible with our studies showing a role for the
      cAMP-dependent pathway in HbF expression. Together, these results demonstrate
      that GM-CSF plays a role in regulating both leukocyte count and HbF expression in
      SCD. Reduction in GM-CSF levels upon hydroxyurea therapy may be critical for
      efficient HbF induction. The results showing the involvement of GM-CSF in HbF
      expression may suggest possible mechanisms for hydroxyurea resistance in SCD.

PMID- 21945575
TI  - Serum TIMP-1 predicts survival outcomes of invasive breast carcinoma patients: a
      meta-analysis.
AB  - BACKGROUND AND AIMS: Tissue inhibitor of metalloproteinase-1 (TIMP-1) is a small
      secretory glycoprotein with multifunctional activity including anti-apoptosis and
      the inhibition of matrix metalloproteinase in invasive breast carcinomas. There
      have been contradictory results as to whether TIMP-1 is a poor or good prognostic
      factor in breast cancer patients. To address this controversy, we conducted a
      meta-analysis for the relationship between TIMP-1 levels and prognostic
      parameters in the breast cancer. METHODS: The relevant published studies were
      pooled according to the defined selection criteria. The effect sizes of overall
      survival and prognostic parameters were calculated by a hazard ratio (HR) or an
      odds ratio (OR). HRs or ORs were combined using a random-effects model. RESULTS:
      Survival outcomes between high or elevated and low or normal serum TIMP-1 levels
      were compared by uni- and multivariate analyses involving 886 and 844 breast
      cancer patients, respectively. Patients with high or elevated serum TIMP-1 levels
      had unfavorable survival outcomes compared to patients with low or normal serum
      TIMP-1 levels in the uni- and multivariate analyses (HR, 1.7 and 2.4; p <0.001
      and p = 0.033, respectively). However, no survival difference was evident in the
      data from tissue TIMP-1 levels by enzyme-linked immunosorbent assay and the
      expression of tissue TIMP-1 mRNA. The high or positive immunohistochemical
      expression of tissue TIMP-1 protein was not related to adjusted and unadjusted
      HRs, lymph node metastasis, and clinical stages. CONCLUSIONS: This meta-analysis
      indicates that serum TIMP-1 levels may be useful for predicting survival outcomes
      of invasive breast cancer patients.

PMID- 21945577
TI  - Development of an immuno-affinity column for ochratoxin analysis using an organic
      solvent-tolerant monoclonal antibody.
AB  - Two kinds of monoclonal antibodies (MoAbs), OCA-10A and OCA-1B, were prepared
      based on their specificity to ochratoxin A (OTA) and ochratoxin B (OTB) and on
      their tolerance to 40% methanol. In an indirect competitive enzyme-linked
      immunosorbent assay, the half maximal inhibitory concentration (IC(50)) value of
      OCA-10A was 27ng/mL for OTA and 17ng/mL for OTB, and that of OCA-1B was 28ng/mL
      for OTA and 13ng/mL for OTB. Immuno-affinity columns (IACs) using these MoAbs
      were prepared with agarose gel beads. The IAC with OCA-1B showed a NaCl-dependent
      binding ability to OTA and OTB, while interestingly, the IAC with OCA-10A bound
      to them without NaCl. The IAC with OCA-10A showed a high methanol tolerance when
      compared with existing IACs, as expected from the high methanol tolerance of OCA
      10A itself. Such tolerance was maintained for the application of the cocoa
      extract with 70% methanol and the wheat extract with 60% acetonitrile, while the
      tolerance was slightly altered by interference from the cocoa extract.
      Examinations with organic solvents at higher concentrations than the allowable
      level in existing IACs showed that OTA and OTB spiked with wheat, cocoa and red
      wine could be purified with high recovery. The newly developed IAC is expected to
      show sufficient clean-up ability for food analyses.

PMID- 21945576
TI  - Biochemical and cell biological analysis of actin in the nematode Caenorhabditis
      elegans.
AB  - The nematode Caenorhabditis elegans has long been a useful model organism for
      muscle research. Its body wall muscle is obliquely striated muscle and exhibits
      structural similarities with vertebrate striated muscle. Actin is the core
      component of the muscle thin filaments, which are highly ordered in sarcomeric
      structures in striated muscle. Genetic studies have identified genes that
      regulate proper organization and function of actin filaments in C. elegans
      muscle, and sequence of the worm genome has revealed a number of conserved
      candidate genes that may regulate actin. To precisely understand the functions of
      actin-binding proteins, such genetic and genomic studies need to be complemented
      by biochemical characterization of these actin-binding proteins in vitro. This
      article describes methods for purification and biochemical characterization of
      actin from C. elegans. Although rabbit muscle actin is commonly used to
      characterize actin-binding proteins from many eukaryotic organisms, we detect
      several quantitative differences between C. elegans actin and rabbit muscle
      actin, highlighting that use of actin from an appropriate source is important in
      some cases. Additionally, we describe probes for cell biological analysis of
      actin in C. elegans.

PMID- 21945578
TI  - Courtship song analysis of Drosophila muscle mutants.
AB  - As part of the mating ritual, males of Drosophila species produce species
      specific courtship songs through wing vibrations generated by the thoracic
      musculature. While previous studies have shown that indirect flight muscles (IFM)
      are neurally activated during courtship song production, the precise role of
      these muscles in song production has not been investigated. Fortunately, IFM
      mutants abound in Drosophila melanogaster and studies spanning several decades
      have shed light on the role of muscle proteins in IFM-powered flight. Analysis of
      courtship songs in these mutants offers the opportunity to uncover the role of
      the IFM in a behavior distinct than flight and subject to different evolutionary
      selection regimes. Here, we describe protocols for the recording and analysis of
      courtship behavior and mating song of D. melanogaster muscle transgenic and
      mutant strains. To record faint acoustic signal of courtship songs, an insulated
      mating compartment was used inside a recording device (INSECTAVOX) equipped with
      a modified electret microphone, a low-noise power supply, and noise filters.
      Songs recorded in the INSECTAVOX are digitized using Goldwave, whose several
      features enable extraction of critical song parameters, including carrier
      frequencies for pulse song and sine song. We demonstrate the utility of this
      approach by showing that deletion of the N-terminal region of the myosin
      regulatory light chain, a mutation known to decrease wing beat frequency and
      flight power, affects courtship song parameters.

PMID- 21945579
TI  - Targeted analysis of tyrosine phosphorylation by immuno-affinity enrichment of
      tyrosine phosphorylated peptides prior to mass spectrometric analysis.
AB  - Tyrosine phosphorylation is a key process that regulates seminal biological
      functions, hence, deregulation of this mechanism is an underlying cause of
      several diseases including cancer and immunological disorders. Due to its low
      abundance, tyrosine phosphorylation is typically under-represented in most of the
      global MS-based phosphoproteomic studies. Here, we describe a selective approach
      based on immuno-affinity purification using specific antibodies to enrich
      tyrosine phosphorylated peptides from a complex proteolytic digest. LC-MS/MS
      analysis is subsequently used for peptide identification allowing the exact
      localization of the phosphorylated residue within the sequence. Using this
      approach more than 1000 non-redundant phosphotyrosine peptides can be identified
      in less than 6h of MS analysis, reflecting the high sensitivity and specificity
      of the technique. The identified tyrosine phosphorylated peptides can be used to
      study different biological aspects of tyrosine signaling and disease.

PMID- 21945580
TI  - Treatment of high-grade glioma with radiolabeled peptides.
AB  - The management of high-grade glioma (HGG) patients in clinical routine represents
      a challenging task. HGG has a poor prognosis because of early recurrence or
      therapy-refractory disease following first-line standard therapy, which includes
      a multidisciplinary approach involving radical surgical resection followed by
      external beam radiation therapy in combination with chemotherapy. Glioma cells
      are known to express specific receptors or glycoproteins on their surface which
      can be used as biological targets for treatment. The application of
      radiopharmaceuticals consisting of a targeting and an effector domain has led to
      the introduction of new treatment approaches, aiming at a tumor-specific
      treatment sparing normal brain tissue. One of these new modalities is the peptide
      receptor radionuclide therapy (PRRT). Peptides labeled with radioactive nuclides
      can bind directly to the tumor cells and deliver high doses of radioactivity
      directly to the tumor tissue. This article reviews the literature for PRRT in
      HGG.

PMID- 21945582
TI  - Dynamics of a multigroup epidemiological model with group-targeted vaccination
      strategies.
AB  - A multigroup SIR epidemiological model is used to study the effects of group
      targeted vaccination strategies on disease control and prevention. The model
      takes into consideration both proportionate and preferential mixing patterns
      between groups. We show that the dynamical behaviors of the model are determined
      by the control reproduction number R(v) and, under certain conditions, by the
      type-reproduction number T(1v). These reproduction numbers provide criteria for
      evaluating control strategies including targeted vaccination programs and
      reduction of interactions between groups. We also illustrate how these
      reproduction numbers can be used to examine the influence of population
      heterogeneities such as group preferences, activity levels, and mixing patterns.
      Criteria are also established for disease eradication from the entire network of
      populations by applying vaccination strategies in one or some sub-populations.

PMID- 21945581
TI  - Multiplex IP-FCM (immunoprecipitation-flow cytometry): Principles and guidelines
      for assessing physiologic protein-protein interactions in multiprotein complexes.
AB  - There is significant interest in the development of methods with the potential to
      increase access to 'the interactome' for both experimental and clinical
      applications. Immunoprecipitation detected by flow cytometry (IP-FCM) is a
      robust, biochemical method that can be used for measuring physiologic protein
      protein interactions (PPI) in multiprotein complexes (MPC) with high sensitivity.
      Because it is based on antibody-mediated capture of protein complexes onto
      microspheres, IP-FCM is potentially compatible with a multiplex platform that
      could allow simultaneous assessment of many physiologic PPI. Here, we consider
      the principles of ambient analyte conditions (AAC) and inter-bead independence,
      and provide a template set of experiments showing how to convert singleplex IP
      FCM to multiplex IP-FCM, including assays to confirm the validity of the
      experimental conditions for data acquisition. We conclude that singleplex IP-FCM
      can be successfully upgraded to multiplex format, and propose that the unique
      strengths of multiplex IP-FCM make it a method that is likely to facilitate the
      acquisition of new PPI data from primary cell sources.

PMID- 21945583
TI  - A mathematical model for the Andean Tiwanaku civilization collapse: climate
      variations.
AB  - We propose a mathematical nonlinear model for the Tiwanaku civilization collapse
      based on the assumption, supported by archeological data, that a drought caused a
      lack of the main resource, water. We evaluate the parameter of our model using
      archaeological data. According to our numerical simulation the population core
      should have decreased from 45,000 to 2000 inhabitants due to lake surface
      contraction.

PMID- 21945584
TI  - Mathematical analysis of the navigational process in homing pigeons.
AB  - In a novel approach based on the principles of dynamic systems theory, we
      analyzed the tracks of pigeons recorded with the help of miniaturized GPS
      recorders. Using the method of time lag embedding, we calculated the largest
      Lyapunov exponent to determine the system's predictability and the correlation
      dimension to estimate the number of factors involved. A low Lyapunov exponent
      around 0.02, which proved to be rather constant over all calculations, indicates
      that the navigational process is almost deterministic. In the distribution of the
      correlation dimension estimates we found three distinctive peaks, at 3.3, 3.7 and
      4.2, indicating that avian navigation is a complex multi-dimensional process,
      involving at least four or five independent factors. Additional factors, as
      indicated by an increase in the correlation dimension, seem to be included as the
      pigeons approach their home loft. This increase in correlation dimension and its
      fractal nature suggest that the various navigational factors can be included as
      required and weighted independently. Neither the correlation dimension nor the
      Lyapunov exponent is affected by increasing familiarity of the pigeons with the
      terrain. This suggests that the navigational strategy is stable with the same
      process controlling the flight across familiar as well as unfamiliar terrain.

PMID- 21945585
TI  - Unraveling the Chinese hamster ovary cell line transcriptome by next-generation
      sequencing.
AB  - The pyrosequencing technology from 454 Life Sciences and a novel assembly
      approach for cDNA sequences with the Newbler Assembler were used to achieve a
      major step forward to unravel the transcriptome of Chinese hamster ovary (CHO)
      cells. Normalized cDNA libraries originating from several cell lines and diverse
      culture conditions were sequenced and the resulting 1.84 million reads were
      assembled into 32,801 contiguous sequences, 29,184 isotigs, and 24,576 isogroups.
      A taxonomic classification of the isotigs showed that more than 70% of the
      assembled data is most similar to the transcriptome of Mus musculus, with most of
      the remaining isotigs being homologous to DNA sequences from Rattus norvegicus.
      Mapping of the CHO cell line contigs to the mouse transcriptome demonstrated that
      9124 mouse transcripts, representing 6701 genes, are covered by more than 95% of
      their sequence length. Metabolic pathways of the central carbohydrate metabolism
      and biosynthesis routes of sugars used for protein N-glycosylation were
      reconstructed from the transcriptome data. All relevant genes representing major
      steps in the N-glycosylation pathway of CHO cells were detected. The present
      manuscript represents a data set of assembled and annotated genes for CHO cells
      that can now be used for a detailed analysis of the molecular functioning of CHO
      cell lines.

PMID- 21945586
TI  - A bioremediation case of an ex-quarry area restored by paper sludge.
AB  - Most paper industry waste is in the form of sludge from paper production and
      recycle process paper. There has been an increasing use of paper sludge in
      environmental restoration, a practice that requires particular attention. This
      issue presents a case which demonstrates how the biogas production related to
      this kind of recovery system can represent a problem for environmental protection
      and public health. The case history relates to a former quarry area restored by
      means of paper sludge. After the filling, a substantial quantity of biogas was
      produced, with an external diffusion to sensible target as well. Initial
      investigations showed that the area was characterized by a large amount of paper
      mill sludge made unstable by anaerobic conditions. To date there are no proven
      technologies for this kind of treatment. In this case, for safety and
      naturalization as agricultural area, new methods of bioremediation were used and,
      in particular, an innovative physical, mechanical and biological intervention,
      based on bio-stabilization of paper mill sludge. The treatment is site-specific,
      based on the in-site paper sludge biostabilisation. To complete the intervention
      and in order to demonstrate its validity an important monitoring activity was
      performed, testing all the phases affected by the biological transformation.

PMID- 21945587
TI  - Using Vaccinia's innate ability to introduce DNA into mammalian cells for
      production of recombinant proteins.
AB  - Production of recombinant protein in mammalian cells is time-consuming, labor
      intensive and costly. While seeking to overcome these limitations, we discovered
      that Vaccinia virus has the innate ability to transfer exogenous plasmid DNA into
      mammalian cells during the infection process. Parameters influencing the
      efficiency of this event were characterized and a quick, simple and inexpensive
      way to produce eukaryotic proteins was established.

PMID- 21945588
TI  - The global distribution and phylogeography of Mycobacterium bovis clonal
      complexes.
AB  - The consequences of the clonality of the Mycobacterium tuberculosis complex are
      described and, in particular, the identification of clonal complexes. Clonal
      complexes are groups of strains all descended from a single cell that was the
      most recent common ancestor (MRCA) of the clonal complex and all bearing
      characteristics derived from the MRCA. Three clonal complexes of Mycobacterium
      bovis have been identified and called African 1, African 2 and European 1.
      Members of each clonal complex have a distinct spoligotype signature and are
      identified by a unique deletion present in each member of the clonal complex. The
      African 1 and African 2 clonal complexes are geographically localised to Central
      West Africa and East Africa, respectively and have not been found in cattle
      outside of these regions. However, the European 1 clonal complex is globally
      distributed and has been identified in the British Isles, former British
      colonies, The Americas as well as Kazakhstan and Korea. It is suggested that
      modern cattle breeds, such as Herefords, bred in the UK in the 18th Century,
      would provide a good vehicle for the global distribution of this closely related
      group of strains. The phylogeography of M. bovis and M. tuberculosis are compared
      and in particular the diversity of M. tuberculosis in Africa, compared with the
      localised dominance of M. bovis clonal complexes, is highlighted. Finally, the
      practical use of M. bovis clonal complexes is reviewed, however, a more
      significant use of M. bovis clonal complexes is to generate testable hypotheses
      to understand the pathogenicity and spread of this important veterinary pathogen.
      This first look at the phylogeography of M. bovis clonal complexes has shown
      surprising geographical localisation of molecular types but also hints strongly
      that much of the worldwide distribution of bovine pathogen resulted from human
      trade in cattle within the last 200 years.

PMID- 21945589
TI  - pknE, a serine/threonine kinase of Mycobacterium tuberculosis modulates multiple
      apoptotic paradigms.
AB  - Mycobacterium tuberculosis, an intracellular pathogen that causes tuberculosis
      has developed multifactorial mechanisms to evade host signaling responses.
      Apoptosis, an important innate host immune response that clears the invading
      pathogen is suppressed by M. tuberculosis to gain persistence. Here, we examined
      the various apoptotic events suppressed by Protein Kinase E, (pknE) a Serine
      Threonine Protein Kinase (STPK) of M. tuberculosis in macrophages infected with
      DeltapknE, a deletion mutant of pknE vs. the wild type strain H(37)Rv using
      microarray. The data showed increased expression of genes involved in apoptosis
      and chemokines with suppressed pro-inflammatory cytokines, co-stimulatory
      molecules, arginase1 and iNOS. The microarray data was validated using qRT-PCR,
      PCR array, oligoGE array, arginase assay and/or ELISA. Furthermore, we analyzed
      the phosphorylation of Akt that promotes cell survival using western blotting.
      DeltapknE infected macrophages reduced the phosphorylation of Akt that correlates
      with the observed apoptotic responses. Experiments performed using exogenous
      nitrate donor, sodium nitro prusside to demonstrate the role of pknE during
      nitrate stress showed similar apoptotic responses to that of endogenous nitrate
      stress in DeltapknE infected macrophages. Our data confirms the role of pknE in
      the intra cellular survival of M. tuberculosis by suppressing apoptosis during
      nitrate stress.

PMID- 21945590
TI  - Phylogenetic analysis of the full genome of rabbit hepatitis E virus (rbHEV) and
      molecular biologic study on the possibility of cross species transmission of
      rbHEV.
AB  - Rabbit HEV strains were isolated in China from farmed rabbits, which may be a
      reservoir of a novel genotype of HEV. However, there is little information
      regarding host range and zoonotic potential of rabbit HEV. A previous study from
      this group identified 25 specific nucleotide positions as possibly being involved
      in specifying the host range of HEV and/or in determining the severity of
      hepatitis E disease, whereas this previous analysis did not extend to the new
      rabbit HEVs. Consequently the complete genome of the rabbit HEV strain ch-bj-n1
      was amplified as overlapping fragments using a combination of reverse
      transcription-nested polymerase chain reaction and rapid amplification of cDNA
      ends. The resulting sequence together with two other rabbit HEVs were compared
      with 91 other HEV isolates representative of genotypes 1-4. Phylogenetic analysis
      showed that the novel rabbit HEV strain should be classified into a new HEV
      genotype which has a closer evolutionary relationship with genotype 3 than
      genotypes 1, 2 and 4, with 20 of the 25 specific nucleotide positions identified
      as being present in rabbit HEV genome. Alpha-helix, hydrophilicity, and surface
      probability plots together with antigenic index analysis of the ORF2 protein were
      all undertaken to investigate the antigenicity of rabbit HEV. The alpha-helix
      plot and antigenicity index of the rabbit ORF2 protein was nearly identical to
      that of genotype 1 HEV isolates from human. Furthermore, 20 possible host range
      determinants in rabbit HEV were identical to those isolates from zoonotic groups,
      which may suggest a potential possibility of cross species transmission of rabbit
      HEV.

PMID- 21945591
TI  - Neuroblastoma aggressiveness in relation to sympathetic neuronal differentiation
      stage.
AB  - Neuroblastoma is a childhood malignancy of the sympathetic neuronal lineage. It
      is a rare disease, but since it is frequently diagnosed during infancy,
      neuroblastoma causes life-long medical follow up of those children that survive
      the disease. It was early recognized that a high tumor cell differentiation stage
      correlates to favorable clinical stage and positive clinical outcome. Today,
      highly differentiated tumors are surgically removed and not further treated.
      Cells of many established human neuroblastoma cell lines have the capacity to
      differentiate when stimulated properly, and these cell lines have been used as
      models for studying and understanding central concepts of tumor cell
      differentiation. One recent aspect of this issue is the observation that tumor
      cells can dedifferentiate and gain a stem cell-like phenotype during hypoxic
      conditions, which was first shown in neuroblastoma. Aberrant or blocked
      differentiation is a central aspect of neuroblastoma genesis. In this review we
      summarize known genetic and non-genetic events in neuroblastoma that might be
      coupled to an aberrant sympathetic neuronal differentiation and thereby
      indirectly influencing tumorigenesis and/or aggressive neuroblastoma behavior.

PMID- 21945592
TI  - Amatoxin and phallotoxin composition in species of the genus Amanita in Colombia:
      a taxonomic perspective.
AB  - Some species in the genus Amanita have a great variety of toxic secondary
      metabolites. They are characterized macroscopically by having a white spore print
      and free gills, and microscopically by the presence of a divergent hymenophoral
      trama. Some species of Amanita present in Colombia were chemically characterized
      by analyzing their toxin composition using HPLC. Samples were collected in oak
      (Quercus humboldtii) and pine (Pinus radiata) forests. Twelve species were
      recovered, Amanita fuligineodisca, Amanita xylinivolva, Amanita flavoconia,
      Amanita rubescens, Amanita bisporigera, Amanita muscaria, Amanita humboldtii,
      Amanita sororcula, Amanita brunneolocularis, Amanita colombiana, Amanita citrina,
      Amanita porphyria as well as two unreported species. Results showed that most of
      the analyzed species have alpha -amanitin in concentrations ranging from 50 ppm
      to 6000 ppm. Concentrations of alpha-amanitin in the pileus were significantly
      greater than in the stipe. Phalloidin and phallacidin were only present in A.
      bisporigera. Chromatographic profiles are proposed as an additional taxonomic
      tool since specific peaks with similar retention times were conserved at the
      species level.

PMID- 21945593
TI  - Executive function in chronic pain patients and healthy controls: different
      cortical activation during response inhibition in fibromyalgia.
AB  - The primary symptom of fibromyalgia (FM) is chronic, widespread pain; however,
      patients report additional symptoms including decreased concentration and memory.
      Performance-based deficits are seen mainly in tests of working memory and
      executive function. Neural correlates of executive function were investigated in
      18 FM patients and 14 age-matched healthy controls during a simple Go/No-Go task
      (response inhibition) while they underwent functional magnetic resonance imaging
      (fMRI). Performance was not different between FM and healthy control, in either
      reaction time or accuracy. However, fMRI revealed that FM patients had lower
      activation in the right premotor cortex, supplementary motor area, midcingulate
      cortex, putamen and, after controlling for anxiety, in the right insular cortex
      and right inferior frontal gyrus. A hyperactivation in FM patients was seen in
      the right inferior temporal gyrus/fusiform gyrus. Despite the same reaction times
      and accuracy, FM patients show less brain activation in cortical structures in
      the inhibition network (specifically in areas involved in response
      selection/motor preparation) and the attention network along with increased
      activation in brain areas not normally part of the inhibition network. We
      hypothesize that response inhibition and pain perception may rely on partially
      overlapping networks, and that in chronic pain patients, resources taken up by
      pain processing may not be available for executive functioning tasks such as
      response inhibition. Compensatory cortical plasticity may be required to achieve
      performance on a par with control groups. PERSPECTIVE: Neural activation (fMRI)
      during response inhibition was measured in fibromyalgia patients and controls. FM
      patients show lower activation in the inhibition and attention networks and
      increased activation in other areas. Inhibition and pain perception may use
      overlapping networks: resources taken up by pain processing may be unavailable
      for other processes.

PMID- 21945594
TI  - Pain education in North American medical schools.
AB  - Knowledgeable and compassionate care regarding pain is a core responsibility of
      health professionals associated with better medical outcomes, improved quality of
      life, and lower healthcare costs. Education is an essential part of training
      healthcare providers to deliver conscientious pain care but little is known about
      whether medical school curricula meet educational needs. Using a novel systematic
      approach to assess educational content, we examined the curricula of Liaison
      Committee on Medical Education-accredited medical schools between August 2009 and
      February 2010. Our intent was to establish important benchmark values regarding
      pain education of future physicians during primary professional training.
      External validation was performed. Inclusion criteria required evidence of
      substantive participation in the curriculum management database of the
      Association of American Medical Colleges. A total of 117 U.S. and Canadian
      medical schools were included in the study. Approximately 80% of U.S. medical
      schools require 1 or more pain sessions. Among Canadian medical schools, 92%
      require pain sessions. Pain sessions are typically presented as part of general
      required courses. Median hours of instruction on pain topics for Canadian schools
      was twice the U.S. median. Many topics included in the International Association
      for the Study of Pain core curriculum received little or no coverage. There were
      no correlations between the types of pain education offered and school
      characteristics (eg, private versus public). We conclude that pain education for
      North American medical students is limited, variable, and often fragmentary.
      There is a need for innovative approaches and better integration of pain topics
      into medical school curricula. PERSPECTIVE: This study assessed the scope and
      scale of pain education programs in U.S. and Canadian medical schools.
      Significant gaps between recommended pain curricula and documented educational
      content were identified. In short, pain education was limited and fragmentary.
      Innovative and integrated pain education in primary medical education is needed.

PMID- 21945596
TI  - A model for Ca2+ oscillations stimulated by the type 5 metabotropic glutamate
      receptor: an unusual mechanism based on repetitive, reversible phosphorylation of
      the receptor.
AB  - In parallel with experimental investigations, the molecular mechanisms
      responsible for Ca(2+) oscillations have been much investigated with
      computational models. In the vast majority of cell-types, these oscillations rely
      on the biphasic regulation of the inositol 1,4,5-trisphosphate (InsP(3)) receptor
      by cytosolic Ca(2+). However, when Ca(2+) oscillations are initiated by agonist
      stimulation of the type 5 metabotropic glutamate (mGlu5) receptor, oscillatory
      behaviour is tightly controlled by repetitive cycles of receptor
      phosphorylation/dephosphorylation leading to the periodic activation/deactivation
      of the G protein-activated signalling cascade downstream of this G protein
      coupled receptor. We present a minimal model for mGlu5 receptor-induced Ca(2+)
      oscillations, taking into account receptor phosphorylation by a protein kinase C
      isoenzyme sensitive to diacylglycerol but not to Ca(2+). Depending on the density
      of receptors and the level of stimulation, the model reproduces Ca(2+)
      oscillations based on either a 'dynamic uncoupling' mechanism or InsP(3) receptor
      dynamics. When based on the former mechanism, Ca(2+) oscillation frequency is
      insensitive to the level of stimulation, while the level of receptor expression
      is a determinant of oscillation frequency. When investigating the conditions for
      the occurrence of oscillations, the model predicts that dynamic uncoupling likely
      relies on a steep relationship between the activity of PKC and the amount of
      phosphorylated mGlu5 receptor. Finally, we use the model to simulate the
      adaptation of the signalling pathway during periods of prolonged stimulation
      associated with receptor desensitization/internalization. The model suggests that
      the existence of both oscillatory mechanisms could allow for a significant
      lengthening of the repetitive Ca(2+) responses under these conditions.

PMID- 21945595
TI  - Design, synthesis and biological evaluation of 2-(substituted phenyl)thiazolidine
      4-carboxylic acid derivatives as novel tyrosinase inhibitors.
AB  - Herein we describe the design, synthesis and biological activities of 2
      (substituted phenyl)thiazolidine-4-carboxylic acid derivatives as novel
      tyrosinase inhibitors. The target compounds 2a-2j were designed and synthesized
      from the structural characteristics of N-phenylthiourea, tyrosinase inhibitor and
      tyrosine, and l-DOPA, the natural substrates of tyrosinase. Among them, (2R/S,4R)
      2-(2,4-dimethoxyphenyl)thiazolidine-4-carboxylic acid (2g) caused the greatest
      inhibition 66.47% at 20 MUM of l-DOPA oxidase activity of mushroom tyrosinase.
      Kinetic analysis of tyrosinase inhibition revealed that 2g is a competitive
      inhibitor. We predicted the tertiary structure of tyrosinase, and simulated the
      docking of mushroom tyrosinase with 2g. These results suggest that the binding
      affinity of 2g with tyrosinase is high. Also, 2g effectively inhibited tyrosinase
      activity and reduced melanin levels in B16 cells treated with alpha-MSH. These
      data strongly suggest that 2g can suppress the production of melanin via the
      inhibition of tyrosinase activity.

PMID- 21945597
TI  - Distribution of glutathione transferases in Gram-positive bacteria and Archaea.
AB  - Glutathione transferases (GSTs) have been widely studied in Gram-negative
      bacteria and the structure and function of several representatives have been
      elucidated. Conversely, limited information is available about the occurrence,
      classification and functional features of GSTs both in Gram-positive bacteria and
      in Archaea. An analysis of 305 fully-sequenced Gram-positive genomes highlights
      the presence of 49 putative GST genes in the genera of both Firmicutes and
      Actinobacteria phyla. We also performed an analysis on 81 complete genomes of the
      Archaea domain. Eleven hits were found in the Halobacteriaceae family of the
      Euryarchaeota phylum and only one in the Crenarchaeota phylum. A comparison of
      the identified sequences with well-characterized GSTs belonging to both Gram
      negative and eukaryotic GSTs sheds light on their putative function and the
      evolutionary relationships within the large GST superfamily. This analysis
      suggests that the identified sequences mainly cluster in the new Xi class, while
      Beta class GSTs, widely distributed in Gram-negative bacteria, are under
      represented in Gram-positive bacteria and absent in Archaea.

PMID- 21945598
TI  - Multimedia support in preoperative patient education for radical prostatectomy:
      the physicians' point of view.
AB  - OBJECTIVE: To systematically assess the physicians' point of view of multimedia
      support in preoperative patient education for radical prostatectomy. METHODS: We
      evaluated the view of physicians performing multimedia supported preoperative
      educations within a randomized controlled trial. Therein 8 physicians educated
      203 patients for radical prostatectomy. RESULTS: All physicians rated multimedia
      supported education better than the standard procedure. Main reasons were better
      comprehensibility, the visual presentation, and greater ease in explaining
      complex issues. Objective time measurement showed no difference between both
      educations. The major disadvantage was the impression, that multimedia supported
      education lasted longer. Moreover, they had the impression that some details
      could be further improved. Given the choice, every physician would decide for
      multimedia support. CONCLUSION: Physicians appreciate multimedia support in
      preoperative education and contrary to their impression, multimedia support does
      not prolong patient education. Therefore, patients and physicians likewise profit
      from multimedia support for education and counseling. PRACTICE IMPLICATIONS: The
      readiness of physicians is a possible obstacle to this improvement, as their view
      is a key factor for the transition to everyday routine. Therefore, our results
      could alleviate this possible barrier for establishing multimedia supported
      education in clinical routine.

PMID- 21945599
TI  - Rescue of synaptic plasticity and spatial learning deficits in the hippocampus of
      Homer1 knockout mice by recombinant Adeno-associated viral gene delivery of
      Homer1c.
AB  - Homer1 belongs to a family of scaffolding proteins that interact with various
      post-synaptic density proteins including group I metabotropic glutamate receptors
      (mGluR1/5). Previous research in our laboratory implicates the Homer1c isoform in
      spatial learning. Homer1 knockout mice (H1-KO) display cognitive impairments, but
      their synaptic plasticity properties have not been described. Here, we
      investigated the role of Homer1 in long-term potentiation (LTP) in the
      hippocampal CA1 region of H1-KO mice in vitro. We found that late-phase LTP
      elicited by high frequency stimulation (HFS) was impaired, and that the induction
      and maintenance of theta burst stimulation (TBS) LTP were reduced in H1-KO. To
      test the hypothesis that Homer1c was sufficient to rescue these LTP deficits, we
      delivered Homer1c to the hippocampus of H1-KO using recombinant adeno-associated
      virus (rAAV). We found that rAAV-Homer1c rescued HFS and TBS-LTP in H1-KO
      animals. Next, we tested whether the LTP rescue by Homer1c was occurring via
      mGluR1/5. A selective mGluR5 antagonist, but not an mGluR1 antagonist, blocked
      the Homer1c-induced recovery of late-LTP, suggesting that Homer1c mediates
      functional effects on plasticity via mGluR5. To investigate the role of Homer1c
      in spatial learning, we injected rAAV-Homer1c to the hippocampus of H1-KO. We
      found that rAAV-Homer1c significantly improved H1-KO performance in the Radial
      Arm Water Maze. These results point to a significant role for Homer1c in synaptic
      plasticity and learning.

PMID- 21945600
TI  - Interscapular brown adipose tissue metabolic reprogramming during cold
      acclimation: Interplay of HIF-1alpha and AMPKalpha.
AB  - BACKGROUND: Brown adipose tissue thermogenic program includes complex molecular
      and structural changes. However, energetic aspects of this process are poorly
      depicted. METHODS: We investigated time-dependent reprogramming of interscapular
      brown adipose tissue (IBAT) energy metabolism during cold-acclimation, as well as
      the effects of nitric oxide (()NO) on those changes. Rats were exposed to cold
      (4+/-1 degrees C) for periods of 1, 3, 7, 12, 21, and 45days, and divided into
      three groups: control, treated with L-arginine, and treated with N(omega)-nitro-L
      arginine methyl ester (L-NAME). RESULTS: In the early phase of cold-acclimation
      (up to 7days), the protein levels of all metabolic parameters and oxidative
      phosphorylation components were below the control. However, metabolic parameters
      and respiratory chain components entered a new homeostatic level in the late
      phase of cold-acclimation. These changes were accompanied with increased protein
      levels of phospho-AMP-dependent protein kinase-alpha (phospho-AMPKalpha) on the
      first day of cold-acclimation, and hypoxia-inducible factor-1alpha (HIF-1alpha)
      throughout early cold-acclimation. L-arginine positively affected protein
      expression of enzymes involved in glucose metabolism and beta-oxidation of fatty
      acids in the early phase of cold-acclimation, and oxidative phosphorylation
      components throughout cold-acclimation. In contrast, L-NAME had the opposite
      effects. CONCLUSION: Results suggest that IBAT structural remodeling is followed
      by energy metabolism reprogramming, which control might be orchestrated by the
      action of AMPKalpha and HIF-1alpha. Data also indicated the involvement of L
      arginine-()NO in the regulation of IBAT metabolism. GENERAL SIGNIFICANCE: Results
      obtained in this study might be of great importance for elucidating regulatory
      pathways governing energy metabolism in both physiological and pathophysiological
      states.

PMID- 21945601
TI  - Exacerbation of X-linked ichthyosis phenotype in a female by inheritance of
      filaggrin and steroid sulfatase mutations.
AB  - BACKGROUND: X-linked ichthyosis (XLI) is a relatively common, recessive condition
      caused by mutations in the steroid sulfatase (STS) gene. Common loss-of-function
      mutations in the filaggrin gene (FLG) cause ichthyosis vulgaris and predispose
      individuals to atopic eczema. OBJECTIVE: To test the hypothesis that co
      inheritance of FLG mutations can act as a genetic modifier in XLI. METHODS: An
      unusually severe XLI phenotype in addition to eczema and mild childhood asthma
      was investigated in a female Indian patient by fluorescent in situ hybridization
      (FISH) for the common STS gene deletion. Direct sequencing of the entire FLG gene
      was also performed. RESULTS: FISH analysis revealed that the proband was
      homozygous for the common STS genomic deletion mutation. Further investigation
      revealed a frame-shift mutation 3672del4 in the gene encoding filaggrin (FLG),
      leading to premature termination of profilaggrin translation. Interestingly, her
      father, who had a very typical mild presentation of XLI, did not carry this FLG
      mutation in addition to his STS deletion. Her mother was a heterozygous carrier
      of the FLG mutation and consistent with this, had mild symptoms of ichthyosis
      vulgaris; she was also a heterozygous carrier of the STS deletion. CONCLUSION:
      This is the second reported case of the modifying effects of FLG null alleles on
      XLI and strengthens the hypothesis that filaggrin defects can synergize with STS
      deficiency to exacerbate the ichthyosis phenotype.

PMID- 21945602
TI  - Calcium signalling in astroglia.
AB  - Astroglia possess excitability based on movements of Ca(2+) ions between
      intracellular compartments and plasmalemmal Ca(2+) fluxes. This "Ca(2+)
      excitability" is controlled by several families of proteins located in the plasma
      membrane, within the cytosol and in the intracellular organelles, most notably in
      the endoplasmic reticulum (ER) and mitochondria. Accumulation of cytosolic Ca(2+)
      can be caused by the entry of Ca(2+) from the extracellular space through
      ionotropic receptors and store-operated channels expressed in astrocytes.
      Plasmalemmal Ca(2+) ATP-ase and sodium-calcium exchanger extrude cytosolic Ca(2+)
      to the extracellular space; the exchanger can also operate in reverse, depending
      of the intercellular Na(+) concentration, to deliver Ca(2+) to the cytosol. The
      ER internal store possesses inositol 1,4,5-trisphosphate receptors which can be
      activated upon stimulation of astrocytes through a multiple plasma membrane
      metabotropic G-protein coupled receptors. This leads to release of Ca(2+) from
      the ER and its elevation in the cytosol, the level of which can be modulated by
      mitochondria. The mitochondrial uniporter takes up Ca(2+) into the matrix, while
      free Ca(2+) exits the matrix through the mitochondrial Na(+)/Ca(2+) exchanger as
      well as via transient openings of the mitochondrial permeability transition pore.
      One of the prominent consequences of astroglial Ca(2+) excitability is
      gliotransmission, a release of transmitters from astroglia which can lead to
      signalling to adjacent neurones.

PMID- 21945604
TI  - Calcium signaling in pluripotent stem cells.
AB  - Pluripotent stem cells represent a new source of biological material allowing the
      exploration of signaling phenomena during normal cell development and
      differentiation. Still, the calcium signaling pathways and intracellular calcium
      responses to various ligands or stress conditions have not been sufficiently
      explored as yet in embryonic or induced pluripotent stem cells and in their
      differentiated offspring. This is partly due to the special culturing conditions
      of these cell types, the rapid morphological and functional changes in
      heterogeneous cell populations during early differentiation, and methodological
      problems in cellular calcium measurements. In this paper, we review the currently
      available data in the literature on calcium signaling in pluripotent stem cells
      and discuss the potential shortcomings of these studies. Various assay methods
      are surveyed for obtaining reliable data both in undifferentiated embryonic stem
      cells and in specific, stem cell-derived human tissues. In this paper, we present
      the modulation of calcium signaling in human embryonic stem cells (hESC) and in
      their derivates; mesenchymal stem cell like (MSCl) cells and cardiac tissues
      using the fluorescent calcium indicator Fluo-4 and confocal microscopy. LPA,
      trypsin and angiotensin II were effective in inducing calcium signals both in
      HUES9 and MSCl cells. Histamine and thrombin induced calcium signal exclusively
      in the MSCl cells, while ATP was effective only in HUES9 cells. There was no
      calcium signal evoked by GABA, even at relatively high concentrations. In stem
      cell-derived cardiomyocytes a rapid increase in the beating rate and an increase
      of the calcium signal peaks could be observed after the addition of adrenaline,
      while verapamil led to a strong decrease in cellular calcium and stopped
      spontaneous contractions in a relaxed state.

PMID- 21945603
TI  - The role of the mineralocorticoid receptor in adipocyte biology and fat
      metabolism.
AB  - Aldosterone controls blood pressure by binding to the mineralocorticoid receptor
      (MR), a ligand-activated transcription factor which regulates critical genes
      controlling salt and water homeostasis in the kidney. In recent years,
      inappropriate MR activation has been shown to trigger deleterious responses in
      various tissues, including vessels, heart and brain, hence promoting vascular
      inflammation, cardiovascular remodeling, endothelial dysfunction, and oxidative
      stress. Moreover, epidemiological studies have shown a clear association between
      aldosterone levels and the incidence of metabolic syndrome. In particular, recent
      work has revealed functional MRs in adipose tissue, where they mediate the
      effects of aldosterone and glucocorticoids, displaying important and specific
      functions involving adipose differentiation, expansion and proinflammatory
      capacity. This recent evidence finally moved MR out of the shadow of the
      glucocorticoid receptor (GR), which had previously been considered the only
      player mediating corticosteroid action in adipose tissue. This has opened a new
      era of research focusing on the complexity and selectivity of MR function in
      adipocyte biology. The aim of this review is to summarize the latest concepts on
      the role of MR in white and brown adipocytes, and to discuss the potential
      benefits of tissue-selective MR blockade in the treatment of obesity and
      metabolic syndrome.

PMID- 21945605
TI  - Impact of chromatin structure and dynamics on PR signaling. The initial steps in
      hormonal gene regulation.
AB  - Gene regulation requires access of transcription factors to DNA sequences of
      target genes, which is limited by the compaction of DNA in chromatin. Based on
      our studies on the Progesterone receptor (PR)-dependent hormonal induction of
      mouse mammary tumor virus (MMTV) promoter we found that remodeling of the various
      levels of chromatin organization is a complex and necessary prerequisite for
      regulation. Two consecutive cycles are essential for transcriptional activation,
      both involving the collaboration between activated protein kinases, histone
      modifying enzymes and ATP-dependent chromatin remodelers. The first cycle ends
      with the displacement of histone H1 and decompaction of higher order chromatin
      structure. The second cycle leads to the displacement of dimers of histones H2A
      and H2B resulting in opening of nucleosomes. In both cases the hormone receptor
      recruits an ATP-dependent chromatin remodeler, whose binding to chromatin is
      stabilized by distinct histone modifications. The final result is to facilitate
      full occupancy of the cis regulatory sites and access for the basal transcription
      machinery. Thus, activation of PR-target genes involves a very rapid coordination
      of enzymatic activities via crosstalk with various kinase-signaling pathways.

PMID- 21945606
TI  - General solutions to poroviscoelastic model of hydrocephalic human brain tissue.
AB  - Hydrocephalus is a well-known disorder of brain fluidic system. It is commonly
      associated with complexities in cerebrospinal fluid (CSF) circulation in brain.
      In this paper, hydrocephalus and shunting surgery which is used in its treatment
      are modeled. Brain tissues are considered to follow a poroviscoelastic
      constitutive model in order to address the effects of time dependence of
      mechanical properties of soft tissues and fluid flow hydraulics. Our solution
      draws from Biot's theory of poroelasticity, generalized to account for
      viscoelastic effects through the correspondence principle. Geometrically, the
      brain is conceived to be spherically symmetric, where the ventricles are assumed
      to be a hollow concentric space filled with cerebrospinal fluid. A generalized
      Kelvin model is considered for the rheological properties of brain tissues. The
      solution presented is useful in the analysis of the disorder of hydrocephalus as
      well as the treatment associated with it, namely, ventriclostomy surgery. The
      sensitivity of the solution to various factors such as aqueduct blockage level
      and trabeculae stiffness is thoroughly analyzed using numerical examples. Results
      indicate that partial aqueduct stenosis may be a cause of hydrocephalus. However,
      only severe occlusion of the aqueduct can cause a significant increase in the
      ventricle and brain's extracellular fluid pressure. Ventriculostomy shunts are
      commonly used as a remedy to hydrocephalus. They serve to reduce the ventricular
      pressure to the normal level. However, sensitivity analysis on the shunt's fluid
      deliverability parameter has shown that inappropriate design or selection of
      design shunt may cause under-drainage or over-drainage of the ventricles.
      Excessive drainage of CSF may increase the normal tensile stress on trabeculae.
      It can cause rupture of superior cerebral veins or damage to trabeculae or even
      brain tissues which in turn may lead to subdural hematoma, a common side-effect
      of the surgery. These Post-Surgery Reaction (PSR) patterns might occur on much
      larger time scales than those of the surgery itself, depending on the flow
      conductivity parameters of the brain. The viscoelastic effects can be significant
      contingent on the long term tissue moduli and their contrast with the initial
      ones.

PMID- 21945607
TI  - Evaluation of red blood cell labelling methods based on a statistical model for
      red blood cell survival.
AB  - The aim of this work is to compare different labelling methods that are commonly
      used to estimate the lifespan of red blood cells (RBCs), e.g. in anaemia of renal
      failure, where the effect of treatment with erythropoietin depends on the
      lifespan of RBCs. A previously developed model for the survival time of RBCs that
      accounts for plausible physiological processes of RBC destruction was used to
      simulate ideal random and cohort labelling methods for RBCs, as well as the flaws
      associated with these methods (e.g. reuse of label and loss of the label from the
      surviving RBCs). Random labelling with radioactive chromium and cohort labelling
      using heavy nitrogen were considered. Blood sampling times were determined for
      RBC survival studies using both labelling methods by applying the theory of
      optimal design. It was assessed whether the underlying parameter values of the
      model are estimable from these studies, and the precision of the parameter
      estimates were calculated. In theory, parameter estimation would be possible for
      both types of ideal labelling methods without flaws. However, flaws associated
      with random labelling are significant and not all parameters controlling RBC
      survival in the model can be estimated with good precision. In contrast, cohort
      labelling shows good precision in the parameter estimates even in the presence of
      reuse and prolonged incorporation of the label. A model based analysis of RBC
      survival studies is recommended in future to account for limitations in
      methodology as well as likely causes of RBC destruction.

PMID- 21945608
TI  - Comparison of cetirizine and diphenhydramine in the treatment of acute food
      induced allergic reactions.

PMID- 21945609
TI  - Development of a prototype wound dressing technology which can detect and report
      colonization by pathogenic bacteria.
AB  - A new methodology for detecting the microbiological state of a wound dressing in
      terms of its colonization with pathogenic bacteria such as Staphylococcus aureus
      or Pseudomonas aeruginosa has been developed. Here we report how stabilized lipid
      vesicles containing self-quenched carboxyfluorescein dye are sensitive to lysis
      only by toxins/virulence factors from P. aeruginosa and S. aureus but not by a
      non-toxic Escherichia coli species. The development of the stabilized vesicles is
      discussed and their response to detergent (triton), bacterial toxin (alpha
      hemolysin) and lipases (phospholipase A(2)). Finally, fabrics with stabilized
      vesicles attached via plasma deposited maleic anhydride coupling are shown
      visibly responding to S. aureus (MSSA 476) and P. aeruginosa (PAO1) but not E.
      coli DH5alpha in a prototype dressing.

PMID- 21945610
TI  - A rapid, sensitive, and selective bioluminescence resonance energy transfer
      (BRET)-based nucleic acid sensing system.
AB  - Here we report the design of a bioluminescence resonance energy transfer (BRET)
      based sensing system that could detect nucleic acid target in 5 min with high
      sensitivity and selectivity. The sensing system is based on adjacent binding of
      oligonucleotide probes labeled with Renilla luciferase (Rluc) and quantum dot
      (Qd) on the nucleic acid target. Here Rluc, a bioluminescent protein that
      generates light by a chemical reaction, is employed as an energy donor, and a
      quantum dot is used as an energy acceptor. Bioluminescence emission of Rluc
      overlaps with the Qd absorption whereas the emission of Qd is shifted from the
      emission of Rluc allowing for monitoring of BRET. In the presence of target, the
      labeled probes bind adjacently in a head-to-head fashion leading to BRET from
      Rluc to Qd upon addition of a substrate coelenterazine. The sensing system could
      detect target nucleic acid in buffer as well as in Escherichia coli cellular
      matrix in 5 min with a detection limit of 0.54 pmol. The ability to detect target
      nucleic acid rapidly in a cellular matrix with high sensitivity will prove highly
      beneficial in biomedical and environmental applications.

PMID- 21945611
TI  - Minimising retinal vessel artefacts in optical coherence tomography images.
AB  - Optical coherence tomography (OCT) is commonly used to investigate the layers of
      the retina including retinal nerve fiber layer (RNFL) and retinal pigment
      epithelium (RPE). OCT images are altered by vessels on the retinal surface
      producing artefacts. We propose a new approach to compensate for these artefacts
      and enhance quality of OCT images. A total of 28 (20 normal and 8 glaucoma
      subjects) OCT images were obtained using Spectralis (Heidelberg, Germany).
      Shadows were detected along the image and compensated by the A-Scan intensity
      difference from surrounding non-affected areas. Images were then segmented and
      the area and thickness of RNFL and RPE were measured and compared. 10 subjects
      were tested twice to determine the effect of this on reproducibility of
      measurements. Shadow-suppressed images reflected the profile of the retinal
      layers more closely when assessed qualitatively, minimising distortion. The
      segmentation of RNFL and RPE thickness demonstrated a mean change of 2.4% +/- 1
      and 6% +/- 1 from the original images. Much larger changes were observed in areas
      with vessels. Reproducibility of RNFL thickness was improved, specifically in the
      higher density vessel location, i.e. inferior and superior. Therefore, OCT images
      can be enhanced by an image processing procedure. Vessel artefacts may cause
      errors in assessment of RNFL thickness and are a source of variability, which has
      clinical implications for diseases such as glaucoma where subtle changes in RNFL
      need to be monitored accurately over time.

PMID- 21945612
TI  - Conceptual and methodological issues in epidemiology: An overview.
AB  - In 2010 a series of workshops on philosophical and methodological issues in
      epidemiology was held at the University of Cambridge. The papers in this volume
      arise from those workshops. This paper represents an effort to identify, in broad
      brush, some of the major conceptual and methodological issues in epidemiology,
      which form the basis of an emerging focus on the philosophy of epidemiology.

PMID- 21945613
TI  - Molecules from apoptotic pathways modulate HIV-1 replication in Jurkat cells.
AB  - The replication of viruses involves control of some aspects of host cell
      homeostasis by modification of target cell metabolism and regulation of the
      apoptotic machinery. It is not well known whether molecules involved in apoptotic
      pathways affect human immunodeficiency virus type 1 (HIV-1) replication and
      regulate viral yields. Using the susceptible Jurkat cell line, we studied the
      relationship of apoptosis-associated molecules with HIV-1 virus production using
      a sensitive real-time RT-PCR assay. Here, we found that expression of
      proapoptotic proteins, including Fas ligand (FasL), FADD, or p53 significantly
      increased HIV-1 virus production. In contrast, the expression of antiapoptotic
      molecules, such as FLIP, Bcl-X(L), and XIAP, decreased HIV-1 virus production.
      Knockdown of Bax with siRNA and FADD with expression of its antisense mRNA also
      inhibited viral replication and the caspase-3 inhibitor, Z-DEVD, and decreased
      virus production. These data indicate that HIV-1 infection regulates the
      apoptosis process to facilitate viral replication and inhibition of apoptosis may
      inhibit HIV-1 replication and cytopathogenesis. We also discuss the effects of
      MAPK signaling pathways and apoptosis on HIV-1 replication.

PMID- 21945614
TI  - Divergent quasispecies evolution in de novo hepatitis C virus infection
      associated with bone marrow transplantation.
AB  - Quasispecies is a remarkable characteristic of hepatitis C virus (HCV) and has
      profound roles in HCV biology and clinical practice. The understanding of HCV
      quasispecies behavior, in particular in acute HCV infection, is valuable for
      vaccine development and therapeutic interference. However, acute HCV infection is
      seldom encountered in clinic practice due to its silent onset. In the present
      study, we reported a unique case of de novo HCV infection associated with the
      transplantation of bone marrow from a HCV-positive donor. HCV quasispecies
      diversity was determined in both the donor and the recipient over a 4-year follow
      up, accompanied with simultaneous measurement of HCV neutralizing antibody.
      Detailed genetic and phylogenetic analyses revealed a divergent quasispecies
      evolution, which was not related to dynamic changes of HCV neutralizing antibody.
      Instead, our data suggested an essential role of the fitness adaptation of
      founder viral population in driving such an evolutionary pattern.

PMID- 21945615
TI  - Transcriptional activation of pig Galbeta1,3GalNAc alpha2,3-sialyltransferase
      (pST3Gal I) gene by TGF-beta1 in porcine kidney PK-15 cells.
AB  - In this study we investigated for the first time the transcriptional regulation
      of pig Galbeta1,3GalNAc alpha2,3-sialyltransferase (pST3Gal I) in response to TGF
      beta1 in porcine kidney PK-15 cells. The pST3Gal I gene was found to span about
      90kb and to be composed of 8 exons including 2 exons in the 5'-untranslated
      region. RT-PCR analysis indicated that the induction of pST3Gal I by TGF-beta1 is
      regulated at the transcriptional level. Functional analysis of the 5'-flanking
      region of the pST3Gal I gene revealed the -1257 to -976 region functions as the
      TGF-beta1-inducible promoter and that the Smad-binding site at -1020 is crucial
      for TGF-beta1-induced expression of pST3Gal I in PK-15 cells. In addition, the
      transcriptional activity of pST3Gal I induced by TGF-beta1 in PK-15 cells was
      strongly inhibited by SIS3, which is a specific Smad-3 inhibitor. In summary, our
      results identified the core promoter region in the pST3Gal I promoter and
      demonstrated that Smad-3 binding to the Samd-3 binding site at -1020 is essential
      for transcriptional activation of pST3Gal I in TGF-beta1-induced PK-15 cells.

PMID- 21945616
TI  - Thyroid-specific gene expression in chondrocytes.
AB  - Previously, we demonstrated that Runx2 (Cbfa1/AML3), a chondrocyte-specific
      transcription factor, is expressed in thyroid glands of mice, where it stimulates
      expression of the thyroglobulin (Tg) gene. Here, we reverse transcribed thyroid
      transcription factor-1 (TTF-1), Pax-8, Tg, thyroid peroxidase (TPO) and Na(+)/I(
      ) symporter (NIS) cDNAs from mouse trachea and bronchus RNA samples, but were
      unable to recover these cDNAs from mouse liver RNA samples. Tg mRNA levels in
      trachea and bronchus were about 5.1% and 2.1% of those in thyroid glands. ATDC-5
      cells, cultured chondrocytes, expressed about 30-fold more Tg mRNA than
      undifferentiated cells. Gel shift and Tg gene reporter assay revealed that TTF-1
      stimulated Tg gene expression in these cells. These results indicate that
      chondrocytes turn on some aspects of the thyroid gene expression program and that
      TTF-1 plays important roles in Tg gene expression in chondrocyte.

PMID- 21945617
TI  - Inhibition of eEF-2 kinase sensitizes human glioma cells to TRAIL and down
      regulates Bcl-xL expression.
AB  - Elongation factor-2 kinase (eEF-2 kinase, also known as calmodulin-dependent
      protein kinase III), is a unique calcium/calmodulin-dependent enzyme that
      inhibits protein synthesis by phosphorylating and inactivating elongation factor
      2 (eEF-2). We previously reported that expression/activity of eEF-2 kinase was up
      regulated in several types of malignancies including Gliomas, and was associated
      with response of tumor cells to certain therapeutic stress. In the current study,
      we sought to determine whether eEF-2 kinase expression affected sensitivity of
      glioma cells to treatment with tumor the necrosis factor-related apoptosis
      inducing ligand (TRAIL), a targeted therapy able to induce apoptosis in cancer
      cells but causes no toxicity in most normal cells. We found that inhibition of
      eEF-2 kinase by RNA interference (RNAi) or by a pharmacological inhibitor (NH125)
      enhanced TRAIL-induced apoptosis in the human glioma cells, as evidenced by an
      increase in apoptosis in the tumor cells treated with eEF-2 kinase siRNA or the
      eEF-2 kinase inhibitor. We further demonstrated that sensitization of tumor cells
      to TRAIL was accompanied by a down-regulation of the anti-apoptotic protein, Bcl
      xL, and that overexpression of Bcl-xL could abrogate the sensitizing effect of
      inhibiting eEF-2 kinase on TRAIL. The results of this study may help devise a new
      therapeutic strategy for enhancing the efficacy of TRAIL against malignant glioma
      by targeting eEF-2 kinase.

PMID- 21945618
TI  - Impairment of the Staufen1-NS1 interaction reduces influenza viral replication.
AB  - Staufen1 (Stau1), a host cellular protein, along with non-structural protein 1
      (NS1), an influenza viral protein, associate with each other during influenza
      viral infection and down-regulation of Stau1 by RNA interference reduces the
      yield of influenza A virus, suggesting a role for Stau1 in viral replication. In
      order to develop a new tool to control influenza A virus, we determined the
      specific regions of Staufen1 protein involved in the interaction with NS1. The
      linker between RBD3 and 4 was isolated as the binding regions. Expression of
      RBD3L, the linker including RBD3, inhibited the interaction between Stau1 and
      NS1, reducing the colocalization of the two proteins in the cytosol and nucleus
      regions. In addition, yield of influenza A virus in RBD3L-expressing cells was
      significantly reduced 36 h after infection. These results suggest that disruption
      of the Stau1-NS1 interaction can be used to control replication of influenza A
      virus, thereby providing a target for the development of antiviral drugs.

PMID- 21945619
TI  - Alternative splicing, a new target to block cellular gene expression by
      poliovirus 2A protease.
AB  - Viruses have developed multiple strategies to interfere with the gene expression
      of host cells at different stages to ensure their own survival. Here we report a
      new role for poliovirus 2A(pro) modulating the alternative splicing of pre-mRNAs.
      Expression of 2A(pro) potently inhibits splicing of reporter genes in HeLa cells.
      Low amounts of 2A(pro) abrogate Fas exon 6 skipping, whereas higher levels of
      protease fully abolish Fas and FGFR2 splicing. In vitro splicing of MINX mRNA
      using nuclear extracts is also strongly inhibited by 2A(pro), leading to
      accumulation of the first exon and the lariat product containing the unspliced
      second exon. These findings reveal that the mechanism of action of 2A(pro) on
      splicing is to selectively block the second catalytic step.

PMID- 21945620
TI  - Multipesticide residue analysis in maize combining acetonitrile-based extraction
      with dispersive liquid-liquid microextraction followed by gas chromatography-mass
      spectrometry.
AB  - A fast and simple gas chromatography-mass spectrometry (GC-MS) method for
      determination of forty-one pesticide residues in maize is introduced. The sample
      preparation involves liquid-liquid partitioning with acetonitrile in presence of
      anhydrous MgSO(4) and NaCl (QuEChERS) followed by dispersive liquid-liquid
      microextraction (DLLME) using carbon tetrachloride as extractive solvent and the
      extract obtained by QuEChERS as dispersive solvent. The main factors influencing
      DLLME efficiency including extractive solvent type and volume as well as the
      volume of dispersive solvent were evaluated in this study. The DLLME procedure
      effectively provides an enrichment of the extract and a cleanup of certain polar
      matrix components, which can maximize the sensitivity when a single quadrupole MS
      is used. For validation purposes, recoveries studies were carried out at two
      concentration levels, yielding recovery rates in the range 70-120% for 82% of the
      analytes. A good linearity and precision, with relative standard deviations
      generally below 20% were obtained for all forty-one pesticides. The limits of
      detection obtained were lower than 19 MUg kg(-1) for more than 63% of the
      analytes. In two of a total of ten samples of maize, residues of lindane,
      tefluthrin, pirimicarb, folpet and bifenthrin were found, although at levels
      below the maximum limit established for this kind of samples.

PMID- 21945621
TI  - Determination of beta-blockers and beta-agonists using gas chromatography and gas
      chromatography-mass spectrometry--a comparative study of the derivatization step.
AB  - There is a growing demand for the rapid screening of multiple beta-blockers and
      beta-agonists in a single analytical run in clinical toxicology, antidoping
      control, forensic and environmental science. Although GC-MS is very often used to
      determine pharmaceuticals from these groups of drugs, the literature data on the
      derivatization and MS analysis of mixtures of these compounds is limited. This
      paper compares and evaluates derivatization procedures for the determination of
      six beta-blockers (acebutolol, atenolol, metoprolol, nadolol, propranolol,
      pindolol) and two beta-agonists (salbutamol, terbutaline) using GC techniques.
      Nineteen different derivatizing reagents (nine of them used for the first time
      with almost all the drugs) were employed in order to obtain a single derivative
      for each target compound with the greatest effectiveness of this reaction.
      Trimethylsilylation, tert-butyldimethylsilylation, acylation (e.g.
      trifluoroacetylation), combined trimethylsilylation and acylation, and the
      formation of cyclized silyl derivatives were carried out and the mass spectra
      (EI, 70 eV) recorded. The influence of the reaction time and temperature on these
      procedures was investigated. Additionally, the effects of the type of solvent and
      the amount of added trimethylchlorosilane (TMCS) on the silylation of the target
      compounds using N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) were tested.
      Among of the five mentioned above derivatization procedures applied -
      trimethylsilylation was found to be the most effective for derivatizing the
      analytes. The best results were obtained with a 1:1 (v/v) mixture of 99% BSTFA+1%
      TMCS and ethyl acetate at 60  degrees C for 30 min. The MS data for different
      types of beta-blocker and beta-agonist derivatives is presented. The information
      in this paper is valuable for scientists working on the determination of beta
      blockers and beta-agonists in biological and environmental matrices.

PMID- 21945622
TI  - Collaborative validation of the quantification method for suspected allergens and
      test of an automated data treatment.
AB  - Previous publications investigated different data treatment strategies for
      quantification of volatile suspected allergens by GC/MS. This publication
      presents the validation results obtained on "ready to inject" samples under
      reproducibility conditions following inter-laboratory ring-testing. The approach
      is based on the monitoring of three selected ions per analyte using two different
      GC capillary columns. To aid the analysts a decisional tree is used for guidance
      during the interpretation of the analytical results. The method is evaluated
      using a fragrance oil concentrate spiked with all suspected allergens to mimic
      the difficulty of a real sample extract or perfume oil. At the concentrations of
      10 and 100mg/kg, imposed by Directive 76/768/EEC for labeling of leave-on and
      rinse-off cosmetics, the mean bias is +14% and -4%, respectively. The method is
      linear for all analytes, and the prediction intervals for each analyte have been
      determined. To speed up the analyst's task, an automated data treatment is also
      proposed. The method mean bias is slightly shifted towards negative values, but
      the method prediction intervals are close to that resulting from the decisional
      tree.

PMID- 21945623
TI  - Dicationic ion-pairing of phosphoric acid diesters post-liquid chromatography and
      subsequent determination by electrospray positive ionization-tandem mass
      spectrometry.
AB  - Several organophosphate triesters are widely used as flame retardants and can be
      metabolized to dibutyl (DBP), diphenyl (DPhP), di(2-ethylhexyl) (DEHP) and di(1,3
      dichloro-2-propyl) (or bis(1,3-dichloro-2-propyl); DDCPP) phosphoric acid,
      respectively. A highly sensitive liquid chromatography-electrospray ionization(+)
      triple quadrupole mass spectrometry (LC-ESI(+)-QQQ-MS/MS) based analysis method
      was presently developed. In this method the target compounds were separated with
      a C(18)-based reversed phase LC column, and decamethonium hydroxide (dicatonic
      reagent) was introduced post-LC to form ion-pairs, which were subsequently
      detected by ESI(+). For the phosphate acid diester ion-pairs, the mass spectra
      showed the most abundant ion to be [(CH(3))(2)N(CH(2))(10)N(CH(3))(3)](+), with
      lesser abundances of [[M-H](-)[(CH(3))(3)N(CH(2))(9)CH(2)](2+)](+) and
      [CH(2)CH(CH(2))(8)N(CH(3))(3)](+). For DDCPP, the fragment ions of [[Cl](
      )[(CH(3))(3)N(CH(2))(10)N(CH(3))(3)](2+)](+) and [[Cl](
      )[(CH(3))(3)N(CH(2))(9)CH(2)](2+)](+) could also be observed. The limits of
      quantitation (LOQs) by LC-ESI(+)-MS/MS (based on multiple reaction monitoring)
      were 0.14, 0.03, 0.14 and 0.02 ng/mL for DPhP, DBP, DDCPP and DEHP, respectively.
      The response was highly linearly correlated (r>0.995) with concentration over the
      range of the LOD to 1000 ng/mL. The matrix effect on ESI+ was negligible for the
      samples in experiment of in vitro metabolism using rat liver microsomes.

PMID- 21945624
TI  - Region- and cell type-selective expression of the evolutionarily conserved Nolz
      1/zfp503 gene in the developing mouse hindbrain.
AB  - Nolz-1/Zfp503, a zinc finger-containing gene, is a mammalian member of the SP1
      related nocA/elb/tlp-1 gene family. Previous studies have shown that Nolz-1
      homologs are important for patterning the rhombomeres in zebrafish hindbrain. We
      therefore studied the expression pattern of Nolz-1 in the developing mouse
      hindbrain. Nolz-1 mRNA expression was detected in the prospective rhombomere 3, 5
      and caudal regions as early as E8.75. After E11.5, Nolz-1-positive cells were
      organized as distinct cell clusters, and they were largely non-overlapped with
      either Pax2-positive or Phox2b-positive domains. Most interestingly, we found
      that Nolz-1 was specifically expressed by Phox2b-negative/Isl1/2-positive somatic
      motor neurons, but not by Phox2b-positive/Isl1/2-positive branchial and visceral
      motor neurons, suggesting that Nolz-1 may regulate development of somatic motor
      neurons in the hindbrain. In addition to be expressed in differentiating post
      mitotic neurons, Nolz-1 was also expressed by progenitor cells in the ventricular
      zone located in the dorsal part of aqueduct and the alar plates of hindbrain,
      which suggests a regulatory role of Nolz-1 in the germinal zone. Taken together,
      based on its domain- and cell type-selective pattern, Nolz-1 may involve in
      regulation of various developmental processes, including regional patterning and
      cell-type specification and differentiation in the developing mouse hindbrain.

PMID- 21945625
TI  - Comparison of surgical performance and short-term clinical outcomes between
      laparoscopic and robotic surgery in distal gastric cancer.
AB  - AIMS: The authors aimed to compare the surgical performance and the short-term
      clinical outcomes of robotic assisted laparoscopic distal gastrectomy (RADG) with
      laparoscopy-assisted distal gastrectomy (LADG) in distal gastric cancer patients.
      METHOD: From April 2009 to August 2010, 62 patients underwent LADG and 30
      patients underwent RADG for preoperative stage I distal gastric cancer by one
      surgeon at the National Cancer Center, Korea. Surgical performance was measured
      using lymph node (LN) dissection time and number of retrieved LNs, which were
      viewed as surrogates of technical ease and oncologic quality. RESULTS: In
      clinicopathologic characteristics, mean age, depth of invasion and stage were
      significantly different between the LADG and RADG group. Mean dissection time at
      each LN station was greater in the RADG group, but no significant intergroup
      difference was found for numbers of retrieved LNs. Furthermore, proximal
      resection margins were smaller, and hospital costs were higher in the RADG group.
      In terms of the RADG learning curve, mean LN dissection time was smaller in the
      late RADG group (n = 15) than in the early RADG group (n = 15) for 4sb/4d, 5, 7
      12a stations, but numbers of retrieved LNs per station were similar. CONCLUSION:
      With the exception of operating time and cost, the numbers of retrieved LNs and
      the short-term clinical outcomes of RADG were found to be comparable to those of
      LADG, despite the surgeon's familiarity with LADG and lack of RADG experience.
      Further studies are needed to evaluate objectively ergonomic comfort and to
      quantify the patient benefits conferred by robotic surgery.

PMID- 21945627
TI  - Gestational weight gain in adolescents: a comparison to the new Institute of
      Medicine recommendations.
AB  - STUDY OBJECTIVE: To examine the gestational weight gain distributions of healthy
      adolescents with optimal birth outcomes and compare them to the current 2009
      Institute of Medicine (IOM) recommendations. DESIGN: Secondary data analysis to
      conduct a population-based, cross-sectional study. SETTING: The Central and
      Finger Lakes regions of New York state (Perinatal Database System). PARTICIPANTS:
      6995 adolescents with healthy singleton pregnancies (1996 to 2002). MAIN OUTCOME
      MEASURES: Percentiles of the gestational weight gain distributions were compared
      within body mass index (BMI) groups categorized using 2 different classification
      schemes: adolescent BMI percentiles and adult BMI cut-points. We compared these
      distributions overall and within racial and age groups. RESULTS: The gestational
      weight gain distribution does not differ considerably when BMI is classified
      using adolescent or adult cutoffs. Adolescents have good birth outcomes across a
      wider gestational weight gain range than recommended by the Institute of Medicine
      regardless of how pre-pregnancy weight status is categorized. For example,
      overweight adolescents by adult cutoffs have a range of gestational weight gain
      from 5.0 kg to 30.0 kg, and overweight adolescents by percentile cutoffs have a
      range from 5.4 kg to 29.5 kg, whereas the IOM range is 7.5-11.5 kg. Black and
      young adolescents have a similar distribution to their white and older
      counterparts. CONCLUSION: Practitioners can safely use the new IOM gestational
      weight gain ranges to monitor weight gain in pregnant adolescent patients using
      adult BMI classifications. Future research should examine the range of
      gestational weight gain in adolescents considering a broader scope of birth and
      maternal outcomes.

PMID- 21945626
TI  - PARP-1 enhances the mismatch-dependence of 5'-directed excision in human mismatch
      repair in vitro.
AB  - End-directed mismatch-provoked excision has been reconstituted in several
      purified systems. While 3'-directed excision displays a mismatch dependence
      similar to that observed in nuclear extracts (~20-fold), the mismatch dependence
      of 5'-directed excision is only 3-4-fold, significantly less than that in
      extracts (8-10-fold). Utilizing a fractionation-based approach, we have isolated
      a single polypeptide that enhances mismatch dependence of reconstituted 5'
      directed excision and have shown it to be identical to poly[ADP-ribose]
      polymerase 1 (PARP-1). Titration of reconstituted excision reactions or PARP-1
      depleted HeLa nuclear extract with purified PARP-1 showed that the protein
      specifically enhances mismatch dependence of 5'-directed excision. Analysis of a
      set of PARP-1 mutants revealed that the DNA binding domain and BRCT fold
      contribute to the regulation of excision specificity. Involvement of the
      catalytic domain is restricted to its ability to poly(ADP-ribosyl)ate PARP-1 in
      the presence of NAD(+), likely through interference with DNA binding. Analysis of
      protein-protein interactions demonstrated that PARP-1 interacts with mismatch
      repair proteins MutSalpha, exonuclease 1, replication protein A (RPA), and as
      previously shown by others, replication factor C (RFC) and proliferating cell
      nuclear antigen (PCNA) as well. The BRCT fold plays an important role in the
      interaction of PARP-1 with the former three proteins.

PMID- 21945628
TI  - How should we treat prepubertal labial adhesions? Retrospective comparison of
      topical treatments: estrogen only, betamethasone only, and combination estrogen
      and betamethasone.
AB  - Labial adhesion is a common finding in prepubertal girls. Traditionally, topical
      estrogen cream application has been the choice of conservative treatment,
      however, topical betamethasone treatment has also recently been employed with
      some success. In this retrospective study, we analysed 131 children with labial
      adhesions. Eleven of 71 (15.4%) patients were treated successfully with topical
      estrogen cream only, and 5 of 32 (15.6%) patients were treated successfully with
      betamethasone cream only. We successfully treated 5 of 28 (28.5%) patients with a
      combination of estrogen and betamethasone creams. The mean time of treatment for
      each regimen of therapy was 4 weeks. There was no significance between the single
      therapy estrogen and single-therapy betamethasone groups (P = 1.00), between
      single-therapy estrogen and the combination therapy (P = .16), and the single
      therapy betamethasone to combination therapy (P = .35) groups. There was also no
      significant difference between combination estrogen and betamethasone therapy and
      the combined data of the single therapies (relative risk 1.85; 95% confidence
      interval 0.89-3.89; P =.11). For the treatment of prepubertal labial adhesions,
      topical estrogen and betamethasone creams were found to have similar success
      rates, with limited satisfactory results. The combination therapy was mildly more
      efficacious than each of the single therapies but was not found to be
      statistically significant. Surgical separation is recommended if conservative
      treatment fails.

PMID- 21945629
TI  - Bloody nipple discharge in infancy: a case report and recommendations for
      management.
AB  - We report a 5-month-old male infant with benign unilateral bloody nipple
      discharge, and we present a brief review of 20 previously described cases of
      bloody nipple discharge in infancy. On the basis of our case and previous
      reports, we offer recommendations for the management of the bloody nipple
      discharge in the first year of life: (1) diagnosis should be based on noninvasive
      diagnostic procedures, in the absence of dubious ultrasound or cytological
      diagnostic findings; (2) the condition resolves spontaneously, and surgical
      intervention should be avoided; (3) manipulation of the nipple can prolong the
      bleeding; (4) antibiotics should be given only in the presence of clear clinical
      and cytological signs of infection; and (5) parent reassurance is an important
      part of infantile bloody nipple discharge management.

PMID- 21945630
TI  - Epithelial ovarian tumors in adolescents: a retrospective pathologic study and a
      critical review of the literature.
AB  - OBJECTIVES: The aim of this study was to further evaluate the pathologic features
      of epithelial ovarian neoplasms and their relative frequency among all ovarian
      tumors in the adolescent population. DESIGN: We conducted a retrospective
      pathologic study of all cases of epithelial ovarian neoplasms in adolescents
      (aged 11-19 years) diagnosed in the pathology laboratory of our hospital over the
      past 25 years. RESULTS: A total of 86 ovarian tumors were identified, including
      23 epithelium-derived ovarian neoplasms (26.7%), 53 germ cell tumors (61.6%), 9
      sex-cord stromal tumors (10.5%) and 1 benign Brenner tumor (1.2%). Most cases of
      epithelial tumors were found in patients 17 years of age or older (14/23 cases,
      60.9%). All tumors were unilateral, and their size ranged from 2.5-21 cm (mean
      11.7 cm). Epithelial tumors were further histologically subtyped into 21 benign
      cystadenomas (14 serous and 7 mucinous) and 2 mucinous borderline tumors.
      CONCLUSIONS: A relatively high frequency of epithelial ovarian neoplasms among
      all ovarian tumors in a purely adolescent population was found in our study. Age
      related selection bias may account at least in part for the discrepancy between
      our data and most previous reports. The most common subtype of epithelial ovarian
      tumor in our series was the benign serous cystadenoma.

PMID- 21945631
TI  - Human ovarian cancer cell morphology, motility, and proliferation are
      differentially influenced by autocrine TGFbeta superfamily signalling.
AB  - TGFbeta superfamily signalling participates in normal and pathophysiologic
      cellular processes. Despite several reports demonstrating active TGFbeta
      superfamily signalling pathways in OvCa cell lines and primary cultures, few
      studies examine their functional outcome. Herein we show that primary human
      ovarian cancer cells possess intact autocrine BMP, TGFbeta and activin
      signalling. Blocking autocrine signalling resulted in differential cellular
      responses affecting cellular morphology, motility and proliferation.
      Additionally, BMP4-induced alterations in morphology and motility are dependent
      on Smad signalling. These results suggest that a balance between BMP and
      TGFbeta/activin signalling may be altered to favour BMP signalling during ovarian
      cancer metastatic progression.

PMID- 21945632
TI  - Influence of separator gel in Sarstedt S-Monovette(r) serum tubes on various
      therapeutic drugs, hormones, and proteins.
AB  - BACKGROUND: A separator or barrier gel is a common component of serum and plasma
      collection tubes. Despite their advantages, the use of these tubes is not
      universally accepted, especially for therapeutic drug monitoring (TDM). The aim
      of this study was to evaluate whether the polyacrylester separator gel in
      Sarstedt S-Monovette?(r) tubes influences the concentration of 10 selected
      parameters (amikacin, vancomycin, valproic acid, acetaminophen, cortisol, free
      thyroxine, thyroid-stimulating hormone, transferrin, prealbumin and
      carcinoembryonic antigen) in a clinically significant way. METHODS: Results from
      patient samples collected in plastic Sarstedt S-Monovette(r) tubes with separator
      gel were compared with those from plain serum sample tubes. Analytes were
      measured in both tubes on 4 consecutive days to study the influence of prolonged
      contact with the separator gel. Between analyses tubes were stored at 4 degrees
      C. Stability was also evaluated over 72 h for each collection tube. When
      statistical differences were detected, the clinical significance was evaluated
      based on the total allowable error (TEa). RESULTS: On day 1 no statistically
      significant differences were observed between samples collected in Sarstedt S
      Monovette(r) tubes with and without separator gel. Statistical differences were
      present from day 2 on, but were not clinically significant. All evaluated
      parameters were clinically stable over 72 h at 4 degrees C based on TEa, except
      for transferrin en fT4. CONCLUSION: The separator gel in Sarstedt S-Monovette(r)
      tubes did not show statistically significant differences on the day of
      phlebotomy. Later on statistically significant differences appeared but except
      for the stability of fT4 and transferrin they all remained clinically
      insignificant.

PMID- 21945633
TI  - A solution for distinguishing Le(a-b-) sera in CA19-9 assays using SphereLight
      180 and Architect i2000 assays.
AB  - BACKGROUND: Measurement of carbohydrate antigen (CA) 19-9 is not applicable in
      patients with Lewis (Le) blood type, Le(a-b-). It is important to distinguish
      cases with Le(a-b-) before CA19-9 measurement. Therefore, we prepared a cut-off
      solution that gives a clear index to distinguish Le(a-b-) sera. METHOD: The
      frequencies of Le blood types and the distribution of the CA19-9 values in each
      Le blood type were examined in 188 healthy subjects. The CA19-9 values for all
      Le(a-b-) sera and for a portion of Le(a-b+) sera exist below the limit of
      quantitation as measured by the SphereLight 180 kit. The cut-off solution, which
      gives a clear cut-off index (COI), was prepared to differentiate Le(a-b-) from
      Le(a-b+), and was evaluated using the SphereLight 180, Architect i2000, UniCel
      DxI 800, Elecsys 2010, and Lumipuls f kits. RESULTS: The COI was calculated as
      the mean +3 SD of the CA19-9 values of a cut-off solution that is adjusted to the
      limit of detection. Both the sensitivities and specificities of the COIs were
      100% using the SphereLight 180 kit and 100% and 91.7%, respectively, using the
      Architect i2000 kit, but these values were not satisfactory using the other CA19
      9 assay kits. CONCLUSION: The COIs, determined by the cut-off solution, correctly
      identified all Le(a-b-) sera as Le(a-b-) and differentiated Le(a-b-) sera from
      other types of sera in CA19-9 assays using only the SphereLight 180 and Architect
      i2000 kits.

PMID- 21945634
TI  - Prediction of the appropriate size of drug molecules that could be released by a
      pulsatile mechanism from pH/thermoresponsive microspheres obtained from preformed
      polymers.
AB  - Preparation of cross-linked pH/thermoresponsive microspheres from preformed
      polymers is still lacking in literature since copolymers possessing both
      temperature- and pH-sensitive units together with a cross-linkable moiety in
      appropriate ratios are required. Moreover, choosing of the appropriate drugs able
      to be loaded and then released in a pulsatile manner is randomly performed. Here,
      we report the synthesis of pH/thermoresponsive cross-linked microspheres based on
      N-isopropylacrylamide and N-alloc-ethylenediamine. A chromatographic method was
      developed to predict the appropriate size of drug molecules that could be loaded
      and then released in a pulsatile manner. Accordingly, it was established that
      common drugs (salicylic acid, benzoic acid, nicotinic acid, lidocaine and
      diclofenac), with molecular weights ranging between 100 and 1000 g mol(-1), could
      be loaded and released in a pulsatile manner. Biologic molecules with higher
      molecular weights (heparin, lysozyme and bovine serum albumin) are completely
      excluded from the pores of cross-linked pH/thermoresponsive microspheres both
      below and above the volume phase transition temperature.

PMID- 21945635
TI  - Seasonal effects on hematological and innate immune parameters in sea bass
      Dicentrarchus labrax.
AB  - The temperate aquatic environment is affected by two primary components of
      season, temperature and photoperiod, during the annual cycle. Many organisms
      respond to seasonal change physiologically, behaviorally or both. The aim of this
      study was to investigate the effect of seasonality on cortisol, hematological and
      innate immune parameters in European sea bass reared under traditional semi
      intensive aquaculture. Sea bass (Dicentrarchus labrax) were reared in an outdoor
      pond and serum cortisol, hematocrit, leucocrit, serum lysozyme activity and total
      glutathione were bimonthly monitored over a 14-months period. The effect of
      seasonality was observed for all parameters carried out, with generally higher
      values in summer and lower in winter. These results could improve the
      understanding of the influence of seasonal cues on the immune system and
      hematological parameters in fish in order to optimize the husbandry practices.

PMID- 21945636
TI  - Antigenic mimicking with cysteine-based cyclized peptides reveals a previously
      unknown antigenic determinant on E2 glycoprotein of classical swine fever virus.
AB  - Envelope glycoprotein E2 of classical swine fever virus (CSFV) is the major
      antigen that induces neutralizing antibodies in infected pigs. The conformational
      epitope(s) on B/C domains were mapped to the N-terminal 90 residues of E2 between
      amino acids 690 and 779 (Chang et al., 2010a). To mimic the conformational
      epitopes, a set of synthetic cyclized peptides spanning the B/C domains of E2
      were used to react with monoclonal antibodies (mAbs) against E2 and with swine
      anti-CSFV polyclonal sera. All antibodies recognized a highest common element,
      (753)RYLASLHKKALPTSV(767), on the double-looped peptides. This epitope region has
      not been revealed previously in the literature. Both substitution-scanning of
      residues (753)RYLASLHKKALPTSV(767) on a double-looped peptide and site-directed
      mutagenesis of expressed E2 demonstrated that residues (761)K, (763)L and (764)P
      were critical for the reactivity with mAbs. In addition, the up- and downstream
      residues (753)R, (754)Y, (755)L and (765)T were also crucial. Alignment showed
      that this stretch of amino acids was relatively conserved among various CSFVs.
      Thus, we identified a motif (753)RYLASLHKKALPT(765), which may be part of group
      specific antigen and important for the structural integrity of conformational
      epitope recognition.

PMID- 21945637
TI  - Small interfering RNA against the 2C genomic region of coxsackievirus B3 exerts
      potential antiviral effects in permissive HeLa cells.
AB  - Coxsackievirus B3 (CVB3) is the most important causal agent of viral heart muscle
      disease, but no specific antiviral drug is currently available. Small interfering
      RNA (siRNA) has been used as an antiviral therapeutic strategy via
      posttranscriptional gene silencing. In this study, eleven siRNAs were designed to
      target seven distinct regions of the CVB3 genome including VP1, VP2, VP3, 2A, 2C,
      3C, and 3D. All of the siRNAs were individually transfected into HeLa cells,
      which were subsequently infected with CVB3. The impacts of RNA interference
      (RNAi) on viral replication were evaluated using five measures: cytopathic effect
      (CPE), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay,
      50% tissue culture infectious dose (TCID(50)), real-time RT-PCR, and Western
      blot. Five of the eleven siRNAs were highly efficient at inhibiting viral
      replication. This was especially true for siRNA-5, which targeted the ATPase 2C.
      However, antiviral activity varied significantly among siRNA-9, -10, and -11 even
      though that they all targeted the 3D region. Our results revealed several
      effective targets for CVB3 silencing, and provided evidence that sequences except
      CRE within the 2C region may also be potential targets for CVB3-specific siRNAs
      design. These data supported a potential role of RNA interference in future
      antiviral intervention therapies.

PMID- 21945638
TI  - Quasispecies as a matter of fact: viruses and beyond.
AB  - We review the origins of the quasispecies concept and its relevance for RNA virus
      evolution, viral pathogenesis and antiviral treatment strategies. We emphasize a
      critical point of quasispecies that refers to genome collectivities as the unit
      of selection, and establish parallels between RNA viruses and some cellular
      systems such as bacteria and tumor cells. We refer also to tantalizing new
      observations that suggest quasispecies behavior in prions, perhaps as a result of
      the same quantum-mechanical indeterminations that underlie protein conformation
      and error-prone replication in genetic systems. If substantiated, these
      observations with prions could lead to new research on the structure-function
      relationship of non-nucleic acid biological molecules.

PMID- 21945639
TI  - Monocular enucleation profoundly reduces secretogranin II expression in adult
      mouse visual cortex.
AB  - Secretogranin II (ScgII), a member of the chromogranin family, is almost
      exclusively found in large dense core vesicles of a wide variety of endocrine and
      neuronal tissues, being stored together with many different neurotransmitters,
      peptide hormones and neuropeptides. In the brain ScgII is almost completely
      processed to secretoneurin, a peptide involved in neurite outgrowth,
      neuroprotection and neuronal plasticity. Furthermore, correlations with
      neurotransmitter release and a variety of neurological diseases were reported. In
      this study we examined possible changes in ScgII mRNA expression in the visual
      system of adult mice after removal of one eye. Mice were monocularly deprived of
      vision and sacrificed 1 day or 1, 3, 5 and 7 weeks after enucleation. Starting 1
      day after the deprivation, a marked decrease of ScgII was visible in the
      contralateral visual cortex. Recovery initiated in the lateral supragranular
      visual cortex after 5 weeks of enucleation, but was far from complete in the 7
      week animals, especially in the monocularly driven medial cortex. By comparison
      with the immediate early gene zif268, it was proven that ScgII cannot be
      categorized as an activity marker, but more likely plays a role in visual system
      plasticity by modulating a range of neurotransmitters and neuropeptides.

PMID- 21945640
TI  - Douglas peritonectomy compared to recto-sigmoid resection in optimally
      cytoreduced advanced ovarian cancer patients: analysis of morbidity and
      oncological outcome.
AB  - BACKGROUND: Rectosigmoidectomy (RR) with primary anastomosis or pelvic
      peritonectomy (PP) are often part of an optimal en bloc tumor resection in
      advanced ovarian cancer (AOC) patients with contiguous extension to or encasement
      of the reproductive organs, peritoneum of the cul-de-sac and sigmoid colon. We
      report our experience with two different surgical approaches in optimally
      cytoreduced AOC patients evaluating oncologic outcome and surgically associated
      morbidities METHODS: Data from all consecutive AOC patients undergoing PP or RR
      as part of the surgical procedure during primary cytoreduction from 2004 through
      2009 were extrapolated and analyzed using the chi-squared test, Cox proportional
      hazard model and Kaplan-Meier method including log-rank test. RESULTS: During the
      study period, we identified 187 AOC patients, fitting the inclusion criteria: 71
      (38%) were submitted to RR and 116 (62%) were managed with PP. The estimated mean
      disease-free survival (DFS) was 30.7 months (95% CI 24.6-36.8) in the RR arm vs.
      25.9 months in the PP arm (95% CI 21.9-29.9) (p 0.299); similarly, the estimated
      mean overall survival (OS) was 38.8 months (95% CI 33.4-44.2) in the RR arm and
      48.2 months in the PP arm (95% CI 43.1-53.3) (p = 0.122). No statistically
      significant differences were found in terms of DFS and OS according to the
      mesocolic lymphnode status (p = 0.65 and p = 0.81, respectively). CONCLUSIONS: In
      conclusion, the current study clearly supports evidence that survival rates are
      similar for patients who achieved optimal residual tumor (RT), independent to
      whether they had RR or PP.

PMID- 21945641
TI  - Immune-mediated myelitis associated with hepatitis virus infections.
AB  - Virus-induced spinal cord damage results from a cytolytic effect on anterior horn
      cells or from predominantly cellular immune-mediated damage of long white matter
      tracts. Infection with the hepatitis virus group, most notably hepatitis C virus,
      has infrequently been associated with the occurrence of myelitis. The
      pathogenesis of hepatitis virus-associated myelitis has not been clarified: virus
      induced autoimmunity (humoral or cell-mediated, possibly vasculitic) seems the
      most likely disease mechanism. Limited available information offers no evidence
      of direct hepatitis virus infection of the spinal cord. Virus neuropenetration
      may occur after virus-infected mononuclear cells penetrate the blood-brain
      barrier, but a true neurolytic effect has not been demonstrated. Attacks of acute
      myelitis usually respond favorably to immunomodulatory therapy. Antiviral therapy
      plays no confirmed role in the treatment of acute bouts of myelitis, but may
      limit the relapsing course of HCV-associated myelitis.

PMID- 21945642
TI  - Biomarkers in clinical trials for neurodegenerative diseases: regulatory
      perspectives and requirements.
AB  - Biomarkers might play comprehensive roles in drug development for
      neurodegenerative diseases and particularly Alzheimer's disease (AD) and other
      dementias. Biomarkers can already be used to better define homogeneous study
      populations (e.g. enriched population at risk for AD) and to select the most
      promising drug candidates in their effective dosages for phase III clinical
      trials, so some biomarkers are currently in the process of implementation as
      primary, co-primary or secondary outcome variables into regulatory guideline
      documents, e.g. regarding phase II in drug development programs as outcome
      measures in proof of concept or dose finding studies. There are specific
      biomarkers available depending on the hypothesized mechanism of action of a
      medicinal product, e.g. impact on the amyloidogenic cascade or on tau
      hyperphosphorylation. However, further validation of specific biomarkers in large
      scale international controlled multicenter studies is necessary before they can
      be accepted as primary outcome measures in pivotal phase III clinical trials.
      There is an even stronger need for rigorous co-development of biological trait-
      and state marker candidates to provide evidence that a medicinal product affects
      the underlying disease process, which, together with clinical improvement, will
      be a precondition for a label of disease modification. Until now no biomarker has
      been sufficiently validated to be acceptable as a surrogate endpoint.
      Establishing of surrogate endpoints is an important goal in neurodegenerative
      diseases, particularly in their early (preclinical, presymptomatic) stages, as
      traditional clinical outcome measures might be too insensitive to change or need
      unfeasible treatment durations for clinical trial conditions. Improvements can
      only be accomplished by active synergistic collaboration between academic,
      industrial and regulatory partners.

PMID- 21945643
TI  - Expression of Semaphorin 4F in neurons and brain oligodendrocytes and the
      regulation of oligodendrocyte precursor migration in the optic nerve.
AB  - Semaphorins are secreted or membrane-anchored proteins that play critical roles
      in neural development and adult brain plasticity. Sema4F is a transmembrane
      semaphorin found on glutamatergic synapses, in which it is attached to the PSD-95
      scaffolding protein. Here we further examined the expression of Sema4F by raising
      specific antibodies. We show that Sema4F protein is widely expressed by neurons
      during neural development and in the adult brain. We also demonstrate a
      preferential localization of this protein in postsynaptic dendrites. Moreover,
      Sema4F is expressed not only by neurons but also by oligodendrocyte precursors in
      the optic nerve and along the migratory pathways of oligodendroglial cells, and
      also by subsets of postnatal oligodendroglial cells in the brain. Finally, in
      vitro experiments demonstrate that endogenous Sema4F expressed by brain cells of
      oligodendroglial lineage regulates the outgrowth migration of oligodendrocyte
      precursors and promotes their differentiation. The present data extend our
      knowledge about the expression of Sema4F and uncover a novel function in the
      control of oligodendrocyte precursor migration in the developing brain.

PMID- 21945644
TI  - Pazopanib, a multitargeted tyrosine kinase inhibitor, reduces diabetic retinal
      vascular leukostasis and leakage.
AB  - OBJECTIVE: To determine the efficacy of pazopanib eye drops in the streptozotocin
      induced diabetic retinopathy rat model. METHODS: A 0.5% w/v pazopanib suspension
      was prepared in phosphate buffered saline (PBS, pH 7.4) in the presence of 0.5%
      w/v sodium carboxymethyl cellulose. Brown Norway rats were divided into three
      groups (n=4) - (1) healthy, (2) diabetic, and (3) diabetic with treatment. The
      drug suspension was administered twice daily as eye drops to group 3 for 30 days.
      Efficacy parameters including the number of adherent leukocytes in the retinal
      vasculature (leukostasis), blood-retinal FITC-dextran leakage, and vitreous-to
      plasma protein ratio were measured. RESULTS: Pazopanib suspension in the form of
      eye drops significantly reduced leukostasis (32%), FITC-dextran leakage (39%),
      and the vitreous-to-plasma protein ratio (64%) in diabetic animals compared to
      untreated diabetic group. CONCLUSION: Pazopanib eye drops can alleviate retinal
      complications of diabetic retinopathy.

PMID- 21945645
TI  - Sun and sky: Does human vision assume a mixture of point and diffuse illumination
      when interpreting shape-from-shading?
AB  - People readily perceive smooth luminance variations as being due to the shading
      produced by undulations of a 3-D surface (shape-from-shading). In doing so, the
      visual system must simultaneously estimate the shape of the surface and the
      nature of the illumination. Remarkably, shape-from-shading operates even when
      both these properties are unknown and neither can be estimated directly from the
      image. In such circumstances humans are thought to adopt a default illumination
      model. A widely held view is that the default illuminant is a point source
      located above the observer's head. However, some have argued instead that the
      default illuminant is a diffuse source. We now present evidence that humans may
      adopt a flexible illumination model that includes both diffuse and point source
      elements. Our model estimates a direction for the point source and then weights
      the contribution of this source according to a bias function. For most people the
      preferred illuminant direction is overhead with a strong diffuse component.

PMID- 21945646
TI  - Swim stress activates serotonergic and nonserotonergic neurons in specific
      subdivisions of the rat dorsal raphe nucleus in a temperature-dependent manner.
AB  - Physical (exteroceptive) stimuli and emotional (interoceptive) stimuli are
      thought to influence stress-related physiologic and behavioral responses through
      different neural mechanisms. Previous studies have demonstrated that stress
      induced activation of brainstem serotonergic systems is influenced by
      environmental factors such as temperature. In order to further investigate the
      effects of environmental influences on stress-induced activation of serotonergic
      systems, we exposed adult male Wistar rats to either home cage control conditions
      or a 15-min swim in water maintained at 19  degrees C, 25  degrees C, or 35 
      degrees C and conducted dual immunohistochemical staining for c-Fos, a marker of
      immediate-early nuclear activation, and tryptophan hydroxylase (TPH), a marker of
      serotonergic neurons. Changes in core body temperature were documented using
      biotelemetry. As expected, exposure to cold (19  degrees C) swim, relative to
      warm (35  degrees C) swim, increased c-Fos expression in the external lateral
      part of the parabrachial nucleus (LPBel), an important part of the
      spinoparabrachial pathway involved in sensation of cold, cutaneous stimuli, and
      in serotonergic neurons in the raphe pallidus nucleus (RPa), an important part of
      the efferent mechanisms controlling thermoregulatory warming responses. In
      addition, exposure to cold (19  degrees C) swim, relative to 35  degrees C swim,
      increased c-Fos expression in the dorsal raphe nucleus, ventrolateral
      part/periaqueductal gray (DRVL/VLPAG) and dorsal raphe nucleus, interfascicular
      part (DRI). Both of these subregions of the dorsal raphe nucleus (DR) have
      previously been implicated in thermoregulatory responses. Altogether, the data
      are consistent with the hypothesis that midbrain serotonergic neurons, possibly
      via activation of afferents to the DR by thermosensitive spinoparabrachial
      pathways, play a role in integration of physiologic and behavioral responses to
      interoceptive stress-related cues involved in forced swimming and exteroceptive
      cues related to cold ambient temperature.

PMID- 21945647
TI  - A food restriction protocol that increases drug reward decreases tropomyosin
      receptor kinase B in the ventral tegmental area, with no effect on brain-derived
      neurotrophic factor or tropomyosin receptor kinase B protein levels in
      dopaminergic forebrain regions.
AB  - Food restriction (FR) decreases brain-derived neurotrophic factor (BDNF)
      expression in hypothalamic and hindbrain regions that regulate feeding and
      metabolic efficiency, while increasing expression in hippocampal and neocortical
      regions. Drugs of abuse alter BDNF expression within the mesocorticolimbic
      dopamine (DA) pathway, and modifications of BDNF expression within this pathway
      alter drug-directed behavior. Although FR produces a variety of striatal
      neuroadaptations and potentiates the rewarding effects of abused drugs, the
      effects of FR on BDNF expression and function within the DA pathway are unknown.
      The primary purpose of the present study was to examine the effect of FR on
      protein levels of BDNF and its tropomyosin receptor kinase B (TrkB) receptor in
      component structures of the mesocorticolimbic pathway. Three to four weeks of FR,
      with stabilization of rats at 80% of initial body weight, did not alter BDNF or
      TrkB levels in nucleus accumbens, caudate-putamen, or medial prefrontal cortex.
      However, FR decreased TrkB levels in the ventral tegmental area (VTA), without
      change in levels of BDNF protein or mRNA. The finding that FR also decreased TrkB
      levels in substantia nigra, with elevation of BDNF protein, suggests that
      decreased TrkB in VTA could be a residual effect of increased BDNF during an
      earlier phase of FR. Voltage-clamp recordings in VTA DA neurons indicated
      decreased glutamate receptor transmission. These data might predict lower average
      firing rates in FR relative to ad libitum fed subjects, which would be consistent
      with previous evidence of decreased striatal DA transmission and upregulation of
      postsynaptic DA receptor signaling. However, FR subjects also displayed elevated
      VTA levels of phospho-ERK1/2, which is an established mediator of synaptic
      plasticity. Because VTA neurons are heterogeneous with regard to neurochemistry,
      function, and target projections, the relationship(s) between the three changes
      observed in VTA, and their involvement in the augmented striatal and behavioral
      responsiveness of FR subjects to drugs of abuse, remains speculative.

PMID- 21945649
TI  - Rubber hands do not cross the midline.
AB  - The rubber hand illusion (RHI) occurs when a person misattributes a fake hand as
      his or her own hand. Previously, the RHI has been examined with both the rubber
      hand and the participant's real hand uncrossed with regards to the participant's
      midline. The present study examined the strength of the illusion when the real
      hand, the fake hand or both hands are placed across the body midline. The
      illusion was induced by stroking the rubber hand and the real hand
      simultaneously. Asynchronous brushing served as a comparable condition since the
      RHI is not seen under these circumstances. Participants indicated where they felt
      their real hand was located by marking a sheet of paper under the table on which
      their unseen hand was placed. A significant RHI was observed with both the hands
      uncrossed. In contrast, no RHI was present when either hand was crossed over the
      midline. Additionally, a shift in hand judgment towards the midline was observed
      when participants crossed their real hand. These results indicate the importance
      of the midline in understanding representations of the body.

PMID- 21945650
TI  - The effect of operant-conditioning balance training on the down-regulation of
      spinal H-reflexes in a spastic patient.
AB  - Spasticity in chronic hemiparetic stroke patients has primarily been treated
      pharmacologically. However, there is increasing evidence that physical
      rehabilitation can help manage hyper-excitability of reflexes (hyperreflexia),
      which is a primary contributor to spasticity. In the present study, one chronic
      hemiparetic stroke patient operantly conditioned the soleus H-reflex while
      training on a balance board for two weeks. The results showed a minimal decrease
      in the Hmax-Mmax ratio for both the affected and unaffected limb, indicating that
      the H-reflex was not significantly altered with training. Alternatively, paired
      reflex depression (PRD), a measure of history-dependent changes in reflex
      excitability, could be conditioned. This was evident by the rightward shift and
      decreased slope of reflex excitability in the affected limb. The non-affected
      limb decreased as well, although the non-affected limb was very sensitive to PRD
      initially, whereas the affected limb was not. Based on these results, it was
      concluded that PRD is a better index of hyperreflexia, and this measurement could
      be more informative of synapse function than simple H-reflexes. This study
      presents a novel and non-pharmacological means of managing spasticity that
      warrants further investigation with the potential of being translated to the
      clinic.

PMID- 21945648
TI  - 14-3-3 proteins as signaling integration points for cell cycle control and
      apoptosis.
AB  - 14-3-3 proteins play critical roles in the regulation of cell fate through
      phospho-dependent binding to a large number of intracellular proteins that are
      targeted by various classes of protein kinases. 14-3-3 proteins play particularly
      important roles in coordinating progression of cells through the cell cycle,
      regulating their response to DNA damage, and influencing life-death decisions
      following internal injury or external cytokine-mediated cues. This review focuses
      on 14-3-3-dependent pathways that control cell cycle arrest and recovery, and the
      influence of 14-3-3 on the apoptotic machinery at multiple levels of regulation.
      Recognition of 14-3-3 proteins as signaling integrators that connect protein
      kinase signaling pathways to resulting cellular phenotypes, and their exquisite
      control through feedforward and feedback loops, identifies new drug targets for
      human disease, and highlights the emerging importance of using systems-based
      approaches to understand signal transduction events at the network biology level.

PMID- 21945651
TI  - Recombinant human erythropoietin reduces aggregation of mutant Cu/Zn-binding
      superoxide dismutase (SOD1) in NSC-34 cells.
AB  - Human erythropoietin (hEPO) has multiple actions in non-hematopoietic tissues,
      including neurotrophic, anti-oxidant, anti-apoptotic, and anti-inflammatory
      effects. To examine the effect of EPO in an vitro model of amyotrophic lateral
      sclerosis (ALS), we stably overexpressed wild SOD1 and a mutant form, SOD1/G93A,
      in NSC-34 motoneuron-like cells. Transformants harboring the wild and mutant
      forms of SOD1 were selected by G418 selection and immunoblot analysis. RT-PCR
      analysis showed that cox-2 expression was increased in the NSC-34/mSOD1s, and MTT
      assays and BrdU-ELISAs revealed reduced cell growth and proliferation in the NSC
      34/mSOD1 cell line. Incubation with 5 or 10IU/mL rhEPO increased the viability
      and decreased the cox-2 expression in the dNSC-34/mSOD1s cells.
      Immunocytochemical staining with anti-SOD1 antibody revealed the presence of
      aggregates of mSOD1 protein in dNSC-34/mSOD1 cells. Incubation with10IU/mL rhEPO
      reduced the proportion of cells containing such aggregates. Our findings suggest
      that the anti-oxidant and anti-inflammatory effects of EPO increase the survival
      of NSC-34/mSOD1 cells and reduce aggregation of the mutant SOD1 protein.

PMID- 21945652
TI  - Activation of group II metabotropic glutamate receptors induces long-term
      depression of excitatory synaptic transmission in the substantia nigra pars
      reticulata.
AB  - Activation of group II metabotropic glutamate receptors (mGlu2 and mGlu3) has
      been implicated as a potential therapeutic strategy for treating both motor
      symptoms and progressive neurodegeneration in Parkinson's disease (PD).
      Modulation of excitatory transmission in the basal ganglia represents a possible
      mechanism by which group II mGlu agonists could exert antiparkinsonian effects.
      Previous studies have identified reversible effects of mGlu2/3 activation on
      excitatory transmission at various synapses in the basal ganglia, including the
      excitatory synapse between the subthalamic nucleus (STN) and the substantia nigra
      pars reticulata (SNr). Using whole-cell patch clamp studies of GABAergic SNr
      neurons in rat midbrain slices, we have found that a prolonged activation of
      group II mGlus by the selective agonist LY379268 induces a long-term depression
      (LTD) of evoked excitatory postsynaptic current (EPSC) amplitude. Bath
      application of LY379268 (100nM, 10min) induced a marked reduction in EPSC
      amplitude, and excitatory transmission remained depressed for at least 40min
      after agonist washout. The effect of LY379268 was concentration-dependent and was
      completely blocked by the group II mGlu-preferring antagonist LY341495 (500nM).
      To determine the relative contributions of mGlu2 and mGlu3 to the LTD induced by
      LY379268, we tested the ability of LY379268 (100nM) to induce LTD in wild type
      mice and mice lacking mGlu2 or mGlu3. LY379268 induced similar LTD in wild type
      mice and mGlu3 knockout mice, whereas LTD was absent in mGlu2 knockout mice,
      indicating that mGlu2 activation is necessary for the induction of LTD in the
      SNr. These studies suggest a novel role for mGlu2 in the long-term regulation of
      excitatory transmission in the SNr and invite further exploration of mGlu2 as a
      therapeutic target for treating the motor symptoms of PD.

PMID- 21945654
TI  - Endurance exercise training enhances cutaneous microvascular reactivity in post
      menopausal women.
AB  - OBJECTIVE: To compare cutaneous microvascular reactivity between untrained young
      and post-menopausal women, and assess the effects of 48 weeks of endurance
      exercise training on cutaneous microvascular reactivity in post-menopausal women.
      METHODS: Twenty post-menopausal and 12 young women completed this study. Using
      laser-Doppler flowmetry, an index of skin blood flow was measured on the forearm
      at rest, during post-occlusive reactive hyperaemia (PORH), and during localised
      heating to 42 degrees C. Cutaneous vascular conductance (CVC) was calculated as
      the ratio of laser-Doppler flow to mean arterial pressure (in AU mm Hg(-1)). For
      the post-menopausal women, this assessment was also performed after 6, 12, 24,
      36, and 48 weeks of endurance exercise training. RESULTS: PORH and maximum CVC
      responses were depressed in untrained post-menopausal women compared with young
      controls (P <= 0.011 for all methods of data expression). PORH was increased
      (P<0.05) in the post-menopausal women after 24 weeks of exercise training (0.51
      +/- 0.16 vs. 0.65 +/- 0.23 AU mm Hg(-1)), with further increases after 36 and 48
      weeks (0.76 +/- 0.27 and 0.88 +/- 0.32 AU mm Hg(-1), respectively). Similarly,
      maximum CVC was increased (P<0.05) after 24 weeks (2.20 +/- 0.31 vs. 2.66 +/-
      0.27 AU mm Hg(-1)), and at the 36-week assessment (2.90 +/- 0.30 AU mm Hg(-1)).
      Cardiopulmonary fitness (VO(2)max) increased after 12 weeks (23.5 +/- 4.4 vs.
      25.4 +/- 5.1 mL kg(-1)min(-1); P<0.05), and improved further throughout the
      intervention (31.6 +/- 5.9 mL kg(-1)min(-1) at week 48). There was a moderate
      positive relationship between the change in PORH (in AU mm Hg(-1)) between weeks
      0 and 48 and the concomitant change in VO(2)max (r=0.65, P=0.002). After 24-36
      weeks of exercise training, the PORH and maximum CVC responses of the post
      menopausal women did not differ to those of the young untrained women (P>0.05).
      CONCLUSION: Cutaneous microvascular reactivity is reduced in post-menopausal
      women compared to young controls and increased to similar levels after 24-36
      weeks of mild-to-moderate endurance exercise.

PMID- 21945655
TI  - Influence of salinity on fertilization and larval development toxicity tests with
      two species of sea urchin.
AB  - Sea urchin embryo-larval development (ELD) and fertilization tests have been
      widely used in ecotoxicity studies and are included in regulatory frameworks.
      Biological processes occur naturally within a range of salinity that depends on
      the species considered. In an attempt to determine the optimum range of salinity,
      ELD and fertilization bioassays were performed at different salinities (15
      40.50/00) with two species of Atlantic sea urchin: Arbacia lixula and
      Paracentrotus lividus. In the ELD assay, the optimum range of salinity was wider
      for A. lixula (29-35.50/00) than for P. lividus (29-330/00). In the fertilization
      assay with P. lividus as a bioindicator species, the highest percentage of
      fertilization (90%) was obtained at salinities of between 29 and 330/00. More
      research on A. lixula is required, since the fertilization success was below 60%.
      The results of the present study demonstrate that salinity may be a confounding
      factor in interpreting ELD test results.

PMID- 21945653
TI  - Soft X-ray microscopy analysis of cell volume and hemoglobin content in
      erythrocytes infected with asexual and sexual stages of Plasmodium falciparum.
AB  - Plasmodium falciparum, the most virulent agent of human malaria, undergoes both
      asexual cycling and sexual differentiation inside erythrocytes. As the
      intraerythrocytic parasite develops it increases in size and alters the
      permeability of the host cell plasma membrane. An intriguing question is: how is
      the integrity of the host erythrocyte maintained during the intraerythrocytic
      cycle? We have used water window cryo X-ray tomography to determine cell
      morphology and hemoglobin content at different stages of asexual and sexual
      differentiation. The cryo stabilization preserves native structure permitting
      accurate analyses of parasite and host cell volumes. Absorption of soft X-rays by
      protein adheres to Beer-Lambert's law permitting quantitation of the
      concentration of hemoglobin in the host cell compartment. During asexual
      development the volume of the parasite reaches about 50% of the uninfected
      erythrocyte volume but the infected erythrocyte volume remains relatively
      constant. The total hemoglobin content gradually decreases during the 48h cycle
      but its concentration remains constant until early trophozoite stage, decreases
      by 25%, then remains constant again until just prior to rupture. During early
      sexual development the gametocyte has a similar morphology to a trophozoite but
      then undergoes a dramatic shape change. Our cryo X-ray tomography analysis
      reveals that about 70% of the host cell hemoglobin is taken up and digested
      during gametocyte development and the parasite eventually occupies about 50% of
      the uninfected erythrocyte volume. The total volume of the infected erythrocyte
      remains constant, apart from some reversible shrinkage at stage IV, while the
      concentration of hemoglobin decreases to about 70% of that in an uninfected
      erythrocyte.

PMID- 21945656
TI  - Activity of upper limb muscles during human walking.
AB  - The EMG activity of upper limb muscles during human gait has rarely been studied
      previously. It was examined in 20 normal volunteers in four conditions: walking
      on a treadmill (1) with unrestrained natural arm swing (Normal), (2) while
      volitionally holding the arms still (Held), (3) with the arms immobilized
      (Bound), and (4) with the arms swinging in phase with the ipsilateral legs, i.e.
      opposite-to-normal phasing (Anti-Normal). Normal arm swing involved weak
      rhythmical lengthening and shortening contractions of arm and shoulder muscles.
      Phasic muscle activity was needed to keep the unrestricted arms still during
      walking (Held), indicating a passive component of arm swing. An active component,
      possibly programmed centrally, existed as well, because some EMG signals
      persisted when the arms were immobilized during walking (Bound). Anti-Normal gait
      involved stronger EMG activity than Normal walking and was uneconomical. The
      present results indicate that normal arm swing has both passive and active
      components.

PMID- 21945657
TI  - Lung cancer histologies associated with emphysema on computed tomography.
AB  - BACKGROUND: Multiple studies have demonstrated an increased risk of lung cancer
      in the presence of emphysema detected visually on computed tomography (CT)
      independent of smoking history and airflow obstruction. The relationship between
      emphysema and specific histologic subtypes of lung cancer remains uncertain.
      OBJECTIVE: To determine the extent to which emphysema on chest CT is associated
      with lung cancer histology. METHODS: Cross-sectional analysis of consecutive lung
      cancer patients referred to the Jewish General Hospital was performed (2001
      2009). All those with demographic data, smoking history (pack-years), documented
      histology and chest CT were included. Emphysema was graded on CT by three
      readers, using a standardized rubric. Odds of each lung cancer subtype were
      compared between patients with and without emphysema, and adjusted for age, sex,
      physician diagnosed COPD and smoking history by multiple logistic regression.
      RESULTS: Complete data were available for 498 lung cancer patients (mean age 68
      years; 44% female; 16% never smokers; 53% without emphysema on CT). The most
      common histologies were adenocarcinoma (242 [49%]), squamous (71 [14%]),
      undifferentiated (48 [10%]) and small cell carcinoma (42 [8%]). The presence of
      emphysema was associated with increased odds of squamous (OR 3.1; 95% CI 1.8-5.3)
      and small cell (OR 2.1; 95% CI 1.1-4.1) carcinoma. After adjustment for age, sex,
      COPD and smoking history, emphysema was associated with squamous (adjusted OR
      2.6; 95% CI 1.4-4.8) but not small cell (adjusted OR 1.5; 95% CI 0.76-3.1)
      carcinoma. Sensitivity analysis was performed by sequential censoring of each
      histologic subtype yielding similar results. Adenocarcinoma was less common in
      the presence of emphysema relative to squamous and small cell carcinoma (adjusted
      OR 0.62; 95% CI 0.41-0.92). When these latter histologies were censored, no
      significant association between adenocarcinoma and emphysema was observed
      (adjusted OR 1.0; 95% CI 0.49-2.1). CONCLUSIONS: Relative to other histologic
      subtypes, the odds of squamous carcinoma were significantly increased among lung
      cancer patients with emphysema after adjustment for age, sex, COPD and smoking
      history. Other common subtypes were not independently associated with emphysema.

PMID- 21945658
TI  - Are EUS-FNA and EBUS-TBNA specimens reliable for subtyping non-small cell lung
      cancer?
AB  - With endosonography, the diagnosis and staging of non-small cell lung cancer
      (NSCLC) increasingly relies on small samples. The discrimination between squamous
      and non-squamous subtypes is now important for therapy tailoring. We analyzed the
      agreement between fine needle aspirates obtained by endosonography and matched
      biopsy samples for subtyping NSCLC. Patients with a positive endoscopic fine
      needle aspirate and a matched biopsy were identified. The level of diagnostic
      agreement was estimated with biopsy samples as golden standard. In 951 patients
      investigated with endosonography, we identified 92 with NSCLC on the positive
      fine needle aspirate and on the matched biopsy. Squamous cell carcinoma was
      diagnosed in 34 (37%) and 44 (48%) of fine needle aspirate and biopsy samples;
      while non-squamous carcinoma was diagnosed in 58 (63%) and 48 (52%) respectively.
      The agreement between needle aspirate and biopsy for the subtyping of NSCLC was
      76% (kappa=0.52). In cases with cell block preparation, the agreement for
      subtyping was 96% (kappa=0.91) vs 69% (kappa=0.39) in cases without cell blocks.
      Therefore, the diagnostic agreement between endosonographic fine needle aspirates
      and biopsy specimens for subtyping NSCLC is moderate with a disagreement in 1 out
      of 4 patients. However, cell block preparation increased the agreement and thus
      the reliability of the fine needle specimens obtained during endosonography, for
      subtyping NSCLC considerably. In conclusion, for patients with NSCLC in whom
      subtyping is relevant, a diagnostic technique yielding larger samples (FNA with
      cell block preparation or biopsies) should be preferred.

PMID- 21945659
TI  - Ground-glass opacity lesions on computed tomography during postoperative
      surveillance for primary non-small cell lung cancer.
AB  - Improvement in chest high-resolution computed tomography (CT) has increased the
      detection of ground-glass opacity (GGO) lesions. However, there is no clear
      therapeutic consensus about concurrent GGO lesions detected during postoperative
      follow-up chest CT after treatment for primary lung cancer. This study
      retrospectively and prospectively investigated 21 patients in whom 53 GGO lesions
      were detected during postoperative follow-up CT of non-small cell lung cancer at
      Kyushu University Hospital from April 2009 to February 2010. We investigated
      clinicopathological factors, such as age, gender, lesion number, size,
      laterality, time of identification, and enlargement or emergence of the inner
      solid component. The malignancy rate of the concurrent GGO lesions was assessed
      by log-rank test in the Kaplan-Meier curves. Twenty percent of the 53 GGO lesions
      had malignant radiological findings during the 5-year follow-up after they were
      first identified by CT. The newly emerging GGO lesions at postoperative CT had
      significantly more malignant radiological findings (39.5%) than other GGO lesions
      (9.5%). Three potentially malignant GGO lesions were treated by surgical
      resection and three were treated by stereotactic radiotherapy. These six treated
      GGO lesions showed a good clinical course without recurrence after treatment.
      Special attention should be paid to newly emerging GGO lesions after resection of
      primary non-small cell lung cancer. It is necessary to select an appropriate
      treatment, taking account of various factors such as the laterality and number of
      GGO lesions or the pathological stage of the postoperative lung cancer.

PMID- 21945660
TI  - Enhancement on biodegradation and anaerobic digestion efficiency of activated
      sludge using a dual irradiation process.
AB  - A dual irradiation process involving aerobic thermophilic irradiation
      pretreatment (ATIP) and intermittent irradiation anaerobic digestion was
      developed to improve the digestion of waste-activated sludge. First, the effect
      of ATIP on further anaerobic digestion of activated sludge in batch mode was
      investigated. When exposed to ATIP for 24 h, the digestion reactor gave the
      highest methane yield, removed the most dissolved organic carbon (DOC) and showed
      the most effective reduction of VS compared to other irradiation times. This
      process was further enhanced by using an anaerobic fluidised-bed reactor packed
      with carbon felt in semi-continuous mode for digesting the pretreated activated
      sludge under intermittent irradiation conditions. Dual irradiation for 24 h
      followed by 60 min of anaerobic irradiation processing per day turned out to be
      optimal. This resulted in 65.3% of VS reduction, 83.9% of DOC removal ratio and
      538 ml/g-VS of methane yield.

PMID- 21945661
TI  - Biofuel production from palm oil with supercritical alcohols: effects of the
      alcohol to oil molar ratios on the biofuel chemical composition and properties.
AB  - Biofuel production from palm oil with supercritical methanol (SCM) and
      supercritical ethanol (SCE) at 400  degrees C and 15 MPa were evaluated. At the
      optimal alcohol to oil molar ratios of 12:1 and 18:1 for the SCM and SCE
      processes, respectively, the biofuel samples were synthesized in a 1.2-L reactor
      and the resulting biofuel was analyzed for the key properties including those for
      the diesel and biodiesel standard specifications. Biofuel samples derived from
      both the SCM and SCE processes could be used as an alternative fuel after slight
      improvement in their acid value and free glycerol content. The remarkable
      advantages of this novel process were: the additional fuel yield of approximately
      of 5% and 10% for SCM and SCE, respectively; the lower energy consumption for
      alcohol preheating, pumping and recovering than the biodiesel production with
      supercritical alcohols that use a high alcohol to oil molar ratio of 42:1.

PMID- 21945662
TI  - Enhanced denitrifying phosphorous removal in a novel anaerobic/aerobic/anoxic
      (AOA) process with the diversion of internal carbon source.
AB  - A novel anaerobic/aerobic/anoxic (AOA) process is proposed to realize
      denitrifying phosphorous removal in this study, and the characteristic of the AOA
      process is transferring part of the anaerobic mixed liquor to the post-anoxic
      zone for providing the carbon source needed for denitrification. The AOA process
      was operated for 3 months, and the average removal efficiencies of NH4+-N, TN and
      PO4(3-)-P were 93.0+/-3.1%, 70.3+/-2.9% and 87.3+/-11.8%, respectively. A mass
      balance analysis indicated that 0.49+/-0.02 g VSS(-1) d(-1) of PO4(3-)-P and
      0.23+/-0.04 g VSS(-1) d(-1) of NO3--N were simultaneously removed in the anoxic
      zone, and it is speculated that denitrifying phosphorous removal occurred in the
      AOA process. Furthermore, 0.24+/-0.06 g VSS(-1) d(-1) of TN was removed in the
      aerobic zone via simultaneous nitrification and denitrification (SND). The
      results demonstrate that the multi-zone structure of the AOA process favors the
      enhancement of denitrifying phosphorous removal and SND for municipal wastewater
      treatment.

PMID- 21945663
TI  - Optimization of medium compositions favoring butanol and 1,3-propanediol
      production from glycerol by Clostridium pasteurianum.
AB  - Medium compositions favoring butanol and 1,3-propanediol (1,3-PDO) production
      from glycerol by Clostridium pasteurianum DSM525 were investigated using
      statistical experimental designs. Medium components affecting butanol and 1,3-PDO
      production were screened using a fractional factorial experimental design. Among
      the six tested variables (phosphate buffer, MnSO4.H2O, MgSO4.7H2O, FeSO4.7H2O,
      (NH4)2SO4, and yeast extract), FeSO4.7H2O, (NH4)2SO4, and yeast extract were
      found to be significant variables for further optimization of medium using a Box
      Behnken design. Optimal butanol (0.98 g/L/h) and 1,3-PDO (1.19 g/L/h)
      productivities were predicted by the corresponding quadratic model for each
      product and the models were validated experimentally under optimized conditions.
      The optimal medium composition for butanol production was significantly different
      from that for 1,3-PDO production (0.06 vs. 0 g/L for FeSO4.7H2O, 7.35 vs. 0 g/L
      for (NH4)2SO4, and 5.08 vs. 8.0 g/L for yeast extract), suggesting that the
      product formation from glycerol by C. pasteurianum DSM525 can be controlled by
      changing medium compositions.

PMID- 21945665
TI  - Structure-function relationship of the saponins from the roots of Platycodon
      grandiflorum for hemolytic and adjuvant activity.
AB  - To assess the contribution of the aglycone and sugar chain to the biological
      activity of saponins from Platycodon grandiflorum, seven structurally consecutive
      saponins, platycodin D (PD), D2 (PD2), D3 (PD3), platycoside A (PA), E (PE),
      deapioplatycoside E (DPE), and polygalacin D2 (PGD) were compared for their
      hemolytic activities and adjuvant potentials on the immune responses to Newcastle
      disease virus-based recombinant avian influenza vaccine (rL-H5) in mice. Among
      seven compounds, the order of the hemolytic activity was PGD ~ PD > PD2 > PA >
      PD3 > PE > DPE. PD, PD2, PA, and PGD significantly not only promoted concanavalin
      A (Con A)-, lipopolysaccharide (LPS)- and antigen-induced splenocyte
      proliferation, but enhanced the NK cell activity in mice immunized with rL-H5. PD
      and PD2 increased the antigen specific IgG, IgG1, IgG2a, and IgG2b antibody
      titers, while PA and PGD only induce the IgG and IgG1 antibody responses in the
      immunized mice. However, the other three saponins were not observed for adjuvant
      activity. The results suggested that the sugar chains attached to C-3, the
      glycidic moiety at C-28 of aglycone, as well as aglycone affect their biological
      activities. Interestingly, their hemolytic and adjuvant activities increased with
      the retention time by reverse phase HPLC analysis. The retention time may be
      useful for primary estimation of fundamental adjuvanticity of saponin with the
      same aglycone.

PMID- 21945664
TI  - Probing the efficacy of peptide-based inhibitors against acid- and zinc-promoted
      oligomerization of amyloid-beta peptide via single-oligomer spectroscopy.
AB  - One avenue for prevention and treatment of Alzheimer's disease involves
      inhibiting the aggregation of amyloid-beta peptide (Abeta). Given the deleterious
      effects reported for Abeta dimers and trimers, it is important to investigate
      inhibition of the earliest association steps. We have employed quantized
      photobleaching of dye-labeled Abeta peptides to characterize four peptide-based
      inhibitors of fibrillogenesis and/or cytotoxicity, assessing their ability to
      inhibit association in the smallest oligomers (n=2-5). Inhibitors were tested at
      acidic pH and in the presence of zinc, conditions that may promote
      oligomerization in vivo. Distributions of peptide species were constructed by
      examining dozens of surface-tethered monomers and oligomers, one at a time.
      Results show that all four inhibitors shift the distribution of Abeta species
      toward monomers; however, efficacies vary for each compound and sample
      environment. Collectively, these studies highlight promising design strategies
      for future oligomerization inhibitors, affording insight into oligomer structures
      and inhibition mechanisms in two physiologically significant environments.

PMID- 21945666
TI  - 3'-Chloro-5,7-dimethoxyisoflavone inhibits TNFalpha-induced CXCL10 gene
      transcription by suppressing the NF-kappaB pathway in HCT116 human colon cancer
      cells.
AB  - Tumor necrosis factor alpha (TNFalpha) is a major inflammatory cytokine that
      plays important roles in progression of tumorigenesis in the tumor
      microenvironment. CXC chemokine ligand 10 (CXCL10), expression of which is
      stimulated by TNFalpha, is involved in tumor migration, invasion, and metastasis.
      3'-Chloro-5,7-dimethoxyisoflavone (CDMF) is a synthetic isoflavone derivative.
      Here, we found that CDMF inhibits TNFalpha-induced invasive motility of human
      colon cancer cells. We tested whether CDMF would inhibit TNFalpha-induced CXCL10
      expression using reverse transcription-PCR, quantitative real-time PCR, and
      enzyme-linked immunosorbent assay in HCT116 cells. CXCL10 expression, stimulated
      by TNFalpha, was suppressed by CDMF. The transcription factor nuclear factor
      kappaB (NF-kappaB) is involved in TNFalpha-induced transcriptional activation of
      the CXCL10 gene promoter. Point mutation of the NF-kappaB binding site abolished
      TNFalpha-induced CXCL10 promoter activity. We next examined the effect of CDMF on
      TNFalpha-induced NF-kappaB activity. CDMF strongly inhibited both TNFalpha
      induced IkappaB phosphorylation on Ser-32 and p65/RelA phosphorylation on Ser
      536. Additionally, CDMF almost blocked TNFalpha-induced NF-kappaB-dependent
      transcriptional activity, as demonstrated by a NF-kappaB cis-acting reporter
      assay. Overall, our results indicate that CDMF suppresses production of CXCL10,
      by TNFalpha, through inhibition of NF-kappaB in HCT116 cells. We propose that
      CDMF may have beneficial effects in reducing TNFalpha-induced inflammatory
      responses, which are essential for tumor development in the colorectal tumor
      microenvironment.

PMID- 21945667
TI  - Heme oxygenase-1 ameliorates LPS-induced acute lung injury correlated with
      downregulation of interleukin-33.
AB  - Although studies have shown that heme oxygenase-1 (HO-1) can abrogate leukocyte
      recruitment and tissue injury after LPS stimulation, the underlying mechanisms
      remain incompletely understood. Interleukin (IL)-33, a new member of the IL-1
      family, is found to play a crucial immunoregulatory effect on the MD2/TLR4
      complex expression. Moreover, TLR4 further promotes the activation of NF-kappaB
      and the production of proinflammatory mediators, which exacerbate neutrophil
      infiltration and organ damage. The present study was designed to determine
      whether the protection of HO-1 against LPS-induced acute lung injury (ALI) is
      involved in downregulation of IL-33. We observed that the levels of IL-33 mRNA
      and protein in LPS-stimulated macrophages were strongly suppressed by a potent HO
      1 inducer, CoPP, treatment. Meanwhile, CoPP significantly reduced the expression
      of TLR4 and TNF-alpha in IL-33-pretreated macrophages followed LPS challenge. In
      the murine model of LPS-induced ALI, CoPP treatment resulted in a remarkable
      decrease in LPS-mediated leukocyte exudation, Evans blue dye albumin (EBA)
      leakage as well as histopathologic disruption. Notably, CoPP treatment markedly
      inhibited the expression of IL-33 and TLR4 in lung tissues under LPS stimulation.
      Therefore, these data suggest that the cytoprotection of HO-1 in LPS-induced
      pulmonary injury is associated with negative regulation of IL-33 and TLR4
      mediated inflammatory response.

PMID- 21945668
TI  - Latent membrane protein 1 of Epstein-Barr virus sensitizes cancer cells to
      cisplatin by enhancing NF-kappaB p50 homodimer formation and downregulating NAPA
      expression.
AB  - Expression of the oncogenic latent membrane protein 1 (LMP1) of Epstein-Barr
      virus is involved in the pathogenesis of nasopharyngeal carcinoma (NPC) and
      lymphoma. In previous studies, we found that expression of LMP1 was sufficient to
      transform BALB/c-3T3 cells. In contrast, other studies have shown that LMP1
      induces apoptosis in a NF-kappaB-dependent manner and also inhibits the growth of
      tumors in mice, thereby indicating that LMP1 may produce various biological
      effects depending on the biological and cellular context. Still, the mechanism
      underlying the pro-apoptotic activity of LMP1 remains unclear. In the present
      study, we found that LMP1 inhibits the expression of NAPA, an endoplasmic
      reticulum SNARE protein that possesses anti-apoptotic properties against the DNA
      damaging drug cisplatin. Accordingly, LMP1-transformed BALB/c-3T3 cells were
      sensitized to cisplatin-induced apoptosis, whereas no sensitization effect was
      noted following treatment with the mitotic spindle-damaging drugs vincristine and
      taxol. Knockdown of LMP1 with antisense oligonucleotides restored NAPA protein
      level and rendered the cells resistant to cisplatin. Similarly, overexpression of
      NAPA reduced the effect of LMP1 and induced resistance to cisplatin. LMP1 was
      shown to upregulate the NF-kappaB subunit p50, leading to formation of p50
      homodimers on the NAPA promoter. These findings suggest that the viral protein
      LMP1 may sensitize cancer cells to cisplatin chemotherapy by downregulating NAPA
      and by enhancing the formation of p50 homodimers which in turn inhibit the
      expression of NF-kappaB regulated anti-apoptotic genes. These findings provide an
      explanatory mechanism for the pro-apoptotic activity of LMP1 as well as new
      therapeutic targets to control tumor growth.

PMID- 21945669
TI  - Change in microstructure and surface properties of electrospray-synthesized
      silica layers.
AB  - Silica layers with different microstructures were prepared by electrospraying.
      The microstructure of the layers was changed by controlling the viscosity of the
      precursor solutions in the electrospray deposition. Precursor solutions of low
      viscosity produced particulated silica layers, exhibiting superhydrophobicity. In
      contrast, fibrous silica layers exhibiting superhydrophilicity were attained with
      viscous precursor solutions. In particular, the particulated silica layers showed
      a good durability and resistance to ultraviolet illumination. The dramatic change
      in the wettability of silica layers without any chemical treatment is promising
      in speeding up their use in many fields.

PMID- 21945670
TI  - Surface and friction forces between grafted polysaccharide layers in the absence
      and presence of surfactant.
AB  - We analyzed the interaction between chemically grafted polysaccharide layers in
      aqueous solutions. To fabricate such layers, an end-terminated dextran silane
      coupling agent was synthesized and the polydextran was grafted to oxidized
      silicon wafers and to silica particles. This resulted in the formation of a 28 nm
      thick layer (in air) and a grafted amount of 40 mg/m(2) as determined by
      ellipsometry. The physical properties of the grafted layer were investigated in
      aqueous solutions by atomic force microscope imaging and colloidal probe force
      measurements. Surface and friction forces were measured between one bare and one
      polydextran coated silica surface. A notable feature was a bridging attraction
      due to affinity between dextran and the silica surface. Surface interactions and
      friction forces were also investigated between two surfaces coated with grafted
      polydextran. Repulsive forces were predominant, but nevertheless a high friction
      force was observed. The repulsive forces were enhanced by addition of sodium
      dodecyl sulfate (SDS) that associates with the tethered polydextran layers. SDS
      also decreased the friction force. Our data suggests that energy dissipation due
      to shear-induced structural changes within the grafted layer is of prime
      importance for the high friction forces observed, in particular deformation of
      protrusions in the surface layer.

PMID- 21945671
TI  - Efficient fabrication of ZrO2-doped TiO2 hollow nanospheres with enhanced
      photocatalytic activity of rhodamine B degradation.
AB  - ZrO(2)-doped TiO(2) hollow nanospheres with anatase phase are efficiently
      fabricated via functionalized negatively charged polystyrene (PS) spheres without
      any surfactant or polyelectrolyte. The resulting Ti(1-)(x)Zr(x)O(2) (hereafter
      denoted as TZ) hollow nanospheres are characterized by scanning electron
      microscopy (SEM), transmission electron microscopy (TEM), powder X-ray
      diffraction (XRD), Laser Raman spectroscopy (LRS), X-ray photoelectron
      spectroscopy (XPS), X-ray fluorescence spectroscopy (XRF), nitrogen sorption, and
      UV-vis diffuse reflectance spectroscopy (UV-vis). The Zr(4+) incorporation
      decreases the anatase crystallite size, increases the specific surface area, and
      changes the pore size distribution. Furthermore, it induces enrichment of
      electron charge density around Ti(4+) ions and blueshift of absorption edges. The
      TZ hollow nanospheres doped with moderate ZrO(2) (molar ratio, Ti:Zr=10:1)
      exhibit better photocatalytic activity than the other samples for the degradation
      of rhodamine B in aqueous solution, which is correlated with the effect of Zr(4+)
      doping on the physicochemical properties in terms of surface structures, phase
      structures, and the electronic structures.

PMID- 21945672
TI  - Sub-minute formation of supported nanoporous mesoscale patterns programmed by
      surface energy.
AB  - We demonstrate an original and powerful concept for elaborating spontaneous, high
      fidelity patterns of nanoporosity from nanoscale building blocks using patterned
      surface chemistry (i.e., "surface energy gating") to corral the growth of
      colloidal structures at a solid surface. Composite films consisting of
      polymethylsilsesquioxane nanoparticles uniformly dispersed in polypropylene
      glycol polymer were examined at temperatures beyond the decomposition of the
      polymer as a function of the substrate surface energy to clarify nanoparticulate
      ensemble behavior. The principle behind this colloidal assembly can be understood
      by taking into consideration the entropy and enthalpy dictating the mutual
      interactions between substrate surface, polymeric solvent, and dispersed colloids
      in the decomposition regime. The relevance of this research is shown by
      demonstrating how the principle of surface energy gating can be utilized to
      achieve spontaneous and controllable spatial patterns of nanoporous, high surface
      area thin films in a cost-effective and energy-efficient manner via brief thermal
      exposure. The simplicity and general nature of this methodology are further
      exemplified by showing the facility with which high-contrast fluorescent
      bioconjugate arrays can be prepared from nanoporous organosilicate patterns.

PMID- 21945673
TI  - Effect of intestinal pressure on fistula closure during vacuum assisted
      treatment: a computational approach.
AB  - BACKGROUND: Enterocutaneous fistulae, pathological communications between the
      intestinal lumen and the abdominal skin, can arise as serious complication of
      gastrointestinal surgery. A current non-surgical treatment for this pathology
      involves topical application of sub-atmospheric pressure, also known as vacuum
      assisted closure (VAC). While this technique appears to be promising, surgeons
      report a number of cases in which its application fails to achieve fistula
      closure. Here, we evaluate the fistula's physical properties during the vacuum
      assisted closure process in a computational approach exploring the relevance of
      intraluminal intestinal pressure. METHODS: A mathematical model formulated by
      differential equations based on tissue elasticity properties and principles of
      fluid mechanics was created and forcing functions were integrated to mimic
      intestinal pressure dynamics. A software to solve equations and to fit the model
      to experimentally obtained data was developed. This enabled simulations of vacuum
      assisted fistula closure under different intestinal pressure. RESULTS: The
      simulation output indicates conditions, in which fistula closure can or cannot be
      expected suggesting favoured or impeded healing, respectively. When modifications
      of intestinal pressure, as observed in fistula accompanying pathologies, are
      integrated, the outcome of fistula closure changes considerably. Rise of
      intestinal pressure is associated with delay of fistula closure and temporary
      fistula radius augmentation, while reduction of intestinal pressure during sub
      atmospheric pressure treatment contributes to a faster and direct fistula
      closure. CONCLUSION: From the model predictions, we conclude that administration
      of intestinal pressure decreasing compounds (e.g. butylscopolamine, glucagon) may
      improve VAC treatment, while intestinal pressure increasing drugs should be
      avoided.

PMID- 21945674
TI  - Swenson's pull-through in older children and adults: peculiar peri-operative
      challenges of surgery.
AB  - INTRODUCTION: The definitive treatment of Hirschsprung's disease is removal of
      the aganglionic bowel by a pull-through surgery. In most cases this surgery is
      performed in infancy or the neonatal period as presentation in older children and
      adulthood is rare. Nevertheless, pull-through in this age group may be necessary
      and present peculiar challenges. MATERIALS/METHODS: A prospective study of
      patients above 5 years with Hirschsprung's disease who presented at LUTH, Lagos
      between January 2007 and July 2010. RESULTS: There were fourteen patients (10
      males and 4 females). The median age was 9 years (range 5-31 years). All the
      patients presented with constipation and abdominal distension. Seven patients
      presented with intestinal obstruction necessitating colostomy. Thirteen patients
      had short segment Hirschsprung's disease limited to the rectosigmoid. The only
      exception had long segment disease with the transition zone located at the
      transverse colon. Ten patients (71.4%) had colostomy before definitive pull
      through while four patients (28.6%) had primary pull-through procedure without a
      colostomy. The definitive pull-through procedure done in all the patients was
      Swenson's abdomino-perineal pull-through and all the patients had a 2-layered
      colo-anal anastomoses. Due to the rigid pelvis in these patients, as well as
      possible scarring, simple blunt dissection was difficult in these cases. The
      median length of follow up was 11 months (range 6-28 months). There was one case
      (7.1%) of mortality. CONCLUSION: Older patients with Hirschsprung's disease
      present with intestinal obstruction and poor nutritional status that may
      necessitate preoperative colostomy. Swenson's pull-through in them poses peculiar
      challenges of mobilization of bowel and achieving a reliable colo-anal
      anastomosis, however, outcome is comparable with surgery in younger children if
      these challenges are overcome.

PMID- 21945675
TI  - Influence of testing conditions on primary stability of arthroscopic knot tying
      for rotator cuff repair: slippery when wet?
AB  - PURPOSE: The purpose was to evaluate whether the knot security of sliding and
      nonsliding knots with different sutures is influenced by dry or wet conditions.
      METHODS: We tested 5 suture materials, all of them US Pharmacopeia No. 2: PDS
      (polydioxanone) II (Ethicon, Somerville, NJ), Ethibond (Ethicon), and 3 ultrahigh
      molecular weight polyethylene (UHMWPE) sutures-FiberWire (Arthrex, Naples, FL),
      Orthocord (DePuy Mitek, Raynham, MA), and Herculine (Linvatec, Largo, FL).
      Testing was performed under dry and wet conditions with sutures soaked in a
      saline solution. Cyclic loading was performed to simulate physiologic conditions.
      We started with a tensile load of 25 N. After 100 cycles, the load was increased
      to 50 N for another 100 cycles. The tensile load was gradually increased by 25 N
      per 100 cycles until suture rupture or knot slippage, defined as lengthening over
      3 mm. RESULTS: Under dry conditions, 170 suture ruptures and 30 knot slippages
      were reported; and under wet testing conditions, 186 suture ruptures and 14 knot
      slippages were reported, with P < .044 and P < .027, respectively. Failure by
      knot slippage (n = 44) was seen under dry and saline solution conditions mainly
      with UHMWPE sutures, in particular with the Herculine suture using a Roeder knot
      showing comparable maximum failure loads in dry (274.5 +/- 58.2 N) and saline
      solution (312.5 +/- 14.2 N) conditions (P > .056). Knot slippage occurred only
      with sliding knots. With the Ethibond suture, no knot slippage was found
      regardless of the testing conditions and knot type. Across all knot types, the
      UHMWPE sutures were significantly stronger with respect to clinical and maximum
      failure loads in ultimate load to failure than Ethibond and PDS II under dry and
      wet testing conditions (P < .001 for both). CONCLUSIONS: We conclude that testing
      of different suture materials and knot types is different in wet versus dry
      conditions and believe that biomechanical testing might be more realistic in a
      wet environment. CLINICAL RELEVANCE: Suture knots behave differently in a wet
      versus dry environment, and testing of knot mechanics might better be carried out
      in wet environments.

PMID- 21945676
TI  - Blocking of sodium and potassium ion-dependent adenosine triphosphatase-alpha1
      with ouabain and vanadate suppresses cell-cell fusion during RANKL-mediated
      osteoclastogenesis.
AB  - To examine the possible enrolment of Na(+)/K(+)-ATPase during osteoclast
      differentiation, Na(+)/K(+)-ATPase inhibitors, including ouabain and vanadate,
      were used in this study. These inhibitors significantly inhibited cell-cell
      fusion of RAW264.7 cells and bone marrow cells induced by RANKL. Interestingly,
      in response to RANKL-stimulation, ouabain and vanadate decreased the number of
      large TRAP+ osteoclasts in the culture of RAW264.7 cells, as well as bone marrow
      cells. In contrast, the number of small TRAP+ osteoclasts either increased in
      RAW264.7 cells or were otherwise less affected in bone marrow cells than large
      TRAP+ osteoclasts. Large TRAP+ osteoclasts are defined as having >= 10
      nuclei/cell and having more potency in bone resorption than small multinuclear
      osteoclasts with <9 nuclei/cell. Na(+)/K(+)-ATPase alpha1 and beta2 mRNAs were
      detected in sRANKL-stimulated RAW264.7 cells. Moreover, real-time quantitative
      PCR showed that ouabain and vanadate suppressed the RANKL-dependent induction of
      the osteoclast fusion-promotion molecule DC-STAMP at the mRNA level. Finally, and
      importantly, RNAi-mediated suppression of Na(+)/K(+)-ATPase alpha1 resulted in a
      diminished number of large TRAP+ osteoclasts in the sRANKL-stimulated RAW264.7
      cells, along with the decreased level of DC-STAMP mRNA expression. These findings
      strongly suggest that blockage of the Na(+)/K(+)-ATPase alpha1 subunit by ouabain
      or vanadate caused the inhibition of RANKL-induced cell-cell fusion, resulting in
      the generation of large osteoclasts through suppression of DC-STAMP expression.
      Thus, in addition to its known function of sodium and potassium ion exchange
      during bone resorption by mature osteoclasts, this study has revealed a novel
      molecular role of the Na(+)/K(+)-ATPase alpha1 subunit in osteoclastogenesis.

PMID- 21945677
TI  - Free radical scavenging and angiotensin-I converting enzyme inhibitory peptides
      from Pacific cod (Gadus macrocephalus) skin gelatin.
AB  - Potent antioxidative peptides were purified from Pacific cod (Gadus
      macrocephalus) skin gelatin using alcalase, neutrase, papain, trypsin, pepsin,
      and alpha-chymotrypsin. Among them, the papain hydrolysate exhibited the highest
      antioxidant activity. Therefore, it was further purified and obtained two
      peptides with amino acid sequences of Thr-Cys-Ser-Pro (388 Da) and Thr-Gly-Gly
      Gly-Asn-Val (485.5 Da). The antioxidant activity of the purified peptides was
      performed by electron spin resonance technique. Moreover, their intracellular
      free radical scavenging activity using 2',7'-dichlorofluorescin diacetate and the
      protective effect against oxidation-induced DNA damage were evaluated in mouse
      macrophages (RAW 264.7 cells). Furthermore, both peptides have shown potential
      angiotensin-I converting enzyme inhibitory effect. The present study demonstrated
      that the peptides derived from Pacific cod (G. macrocephalus) skin gelatin could
      be used in the food industry as functional ingredients with potent antioxidative
      and antihypertensive benefits.

PMID- 21945679
TI  - Facilitated intracellular delivery of peptide-guided nanoparticles in tumor
      tissues.
AB  - Macromolecular nanoparticles can extravasate and accumulate within tumor tissues
      via the passive targeting system, reflecting enhanced permeability and the
      retention effect. However, the unsatisfactory tumor therapeutic efficacy of the
      passive-targeting system, attributable to the retention of extravasated
      nanoparticles in the vicinity of tumor vessels, argues that a new system that
      facilitates intracellular delivery of nanoparticles within tumors is needed.
      Here, we developed hydrophobically modified glycol chitosan (HGC) nanoparticles
      conjugated with interleukin-4 receptor (IL-4R) binding peptides, termed I4R, and
      tested them in mice bearing IL-4R-positive tumors. These HGC-I4R nanoparticles
      exhibited enhanced IL-4R-dependent cellular uptake in tumors compared to
      nonconjugated nanoparticles, leading to better therapeutic and imaging efficacy.
      We conclude that I4R facilitates and enhances cellular uptake of nanoparticles in
      tumor tissues. This study suggests that the intracelluar uptake of nanoparticles
      in tumors is an essential factor to consider in designing nanoparticles for tumor
      targeted drug delivery and imaging.

PMID- 21945678
TI  - Carboxymethylation of polysaccharides from Auricularia auricula and their
      antioxidant activities in vitro.
AB  - The chemical carboxymethylated polysaccharide (CMAAP), which is derived from the
      poorly water-soluble, crude polysaccharide from Auricularia auricula (AAP), was
      prepared. The degree of substitution of CMAAP was 0.857, and its solubility in
      water reached 0.6 mg/mL, much higher than that of AAP (0.1 mg/mL). One fraction,
      CMAAP22, was purified. Chemical analysis indicated that CMAAP22 was composed of
      mannose and glucose in a ratio of 1.06:1 with a molecular weight of 3.4 *
      10(6)Da. IR spectra and (13)C NMR spectra indicated that the C2, C4 and C6
      positions were partially substituted by -CH(2)COOH. AFM revealed that CMAAP22 was
      spherical particle structure with a diameter of 80-300 nm. Moreover, the
      antioxidant activity of CMAAP22 was improved, nearly twice as much as that of the
      AAP, especially in the scavenging of DPPH and ABTS+.

PMID- 21945681
TI  - Efficient GLP-1 gene delivery using two-step transcription amplification plasmid
      system with a secretion signal peptide and arginine-grafted bioreducible polymer.
AB  - Glucagon-like peptide (GLP-1) encoding dual plasmid (pDNA) system (TSTA (SP-GLP
      1)) which is composed of pbeta-Gal4-p65 and pUAS-SP-GLP-1 was constructed to
      improve the production and secretion of expressed GLP-1 by combining the
      advantages of signal peptide (SP) and two-step transcription amplification (TSTA)
      system. Its potential for GLP-1 gene delivery system was investigated with
      employment of arginine-grafted bioreducible polymer (ABP) as a gene carrier.
      Their polyplexes have about 140nm-sizes and 20mV Zeta-potential values. ABP
      showed no cytotoxicity contrary to PEI25k. It was found in RT-PCR experiments
      that TSTA-SP pDNA systems showed increased GLP-1 gene transcription level in
      comparison with mono pDNA system (pbeta-GLP-1). It was also observed in GLP-1
      ELISA that GLP-1 secretion level of TSTA (SP-GLP-1) pDNA system was 2.7-3.4 times
      higher than those of pbeta-GLP-1 and 1.5-1.7 times than TSTA (GLP-1).
      Additionally, 2.5-3.5 folds increased level of GLP-1 secretion was found in ABP
      gene carrier system in comparison with PEI25k. When transfection medium
      containing secreted GLP-1 was transferred to NIT-1 insulinoma cells, the highest
      secretion level of insulin was induced in ABP/TSTA (SP-GLP-1) polyplex medium
      treated cells. Therefore, this novel system could be utilized as a safe and
      efficient GLP-1 gene delivery system for type 2 diabetes therapy.

PMID- 21945680
TI  - Polyplex-microbubble hybrids for ultrasound-guided plasmid DNA delivery to solid
      tumors.
AB  - Microbubble ultrasound contrast agents are being developed as image-guided gene
      carriers for targeted delivery in vivo. In this study, novel polyplex
      microbubbles were synthesized, characterized and evaluated for systemic
      circulation and tumor transfection. Branched polyethylenimine (PEI; 25 kDa) was
      modified with polyethylene glycol (PEG; 5 kDa), thiolated and covalently attached
      to maleimide groups on lipid-coated microbubbles. The PEI-microbubbles
      demonstrated increasingly positive surface charge and DNA loading capacity with
      increasing maleimide content. The in vivo ultrasound contrast persistence of PEI
      microbubbles was measured in the healthy mouse kidney, and a two-compartment
      pharmacokinetic model accounting for free and adherent microbubbles was developed
      to describe the anomalous time-intensity curves. The model suggested that PEI
      loading dramatically reduced free circulation and increased nonspecific adhesion
      to the vasculature. However, DNA loading to form polyplex-microbubbles increased
      circulation in the bloodstream and decreased nonspecific adhesion. PEI
      microbubbles coupled to a luciferase bioluminescence reporter plasmid DNA were
      shown to transfect tumors implanted in the mouse kidney. Site-specific delivery
      was achieved using ultrasound applied over the tumor area following bolus
      injection of the DNA/PEI-microbubbles. In vivo imaging showed over 10-fold higher
      bioluminescence from the tumor region compared to untreated tissue. Ex vivo
      analysis of excised tumors showed greater than 40-fold higher expression in tumor
      tissue than non-sonicated control (heart) tissue. These results suggest that the
      polyplex-microbubble platform offers improved control of DNA loading and
      packaging suitable for ultrasound-guided tissue transfection.

PMID- 21945682
TI  - Controlled permeation of cell membrane by single bubble acoustic cavitation.
AB  - Sonoporation is the membrane disruption generated by ultrasound and has been
      exploited as a non-viral strategy for drug and gene delivery. Acoustic cavitation
      of microbubbles has been recognized to play an important role in sonoporation.
      However, due to the lack of adequate techniques for precise control of cavitation
      activities and real-time assessment of the resulting sub-micron process of
      sonoporation, limited knowledge has been available regarding the detail processes
      and correlation of cavitation with membrane disruption at the single cell level.
      In the current study, we developed a combined approach including optical,
      acoustical, and electrophysiological techniques to enable synchronized
      manipulation, imaging, and measurement of cavitation of single bubbles and the
      resulting cell membrane disruption in real-time. Using a self-focused femtosecond
      laser and high frequency ultrasound (7.44MHz) pulses, a single microbubble was
      generated and positioned at a desired distance from the membrane of a Xenopus
      oocyte. Cavitation of the bubble was achieved by applying a low frequency
      (1.5MHz) ultrasound pulse (duration 13.3 or 40MUs) to induce bubble collapse.
      Disruption of the cell membrane was assessed by the increase in the transmembrane
      current (TMC) of the cell under voltage clamp. Simultaneous high-speed bright
      field imaging of cavitation and measurements of the TMC were obtained to
      correlate the ultrasound-generated bubble activities with the cell membrane
      poration. The change in membrane permeability was directly associated with the
      formation of a sub-micrometer pore from a local membrane rupture generated by
      bubble collapse or bubble compression depending on ultrasound amplitude and
      duration. The impact of the bubble collapse on membrane permeation decreased
      rapidly with increasing distance (D) between the bubble (diameter d) and the cell
      membrane. The effective range of cavitation impact on membrane poration was
      determined to be D/d=0.75. The maximum mean radius of the pores was estimated
      from the measured TMC to be 0.106+/-0.032MUm (n=70) for acoustic pressure of
      1.5MPa (duration 13.3MUs), and increased to 0.171+/-0.030MUm (n=125) for acoustic
      pressure of 1.7MPa and to 0.182+/-0.052MUm (n=112) for a pulse duration of 40MUs
      (1.5MPa). These results from controlled cell membrane permeation by cavitation of
      single bubbles revealed insights and key factors affecting sonoporation at the
      single cell level.

PMID- 21945683
TI  - Synthesis of poly(aminopropyl/methyl)silsesquioxane particles as effective Cu(II)
      and Pb(II) adsorbents.
AB  - Poly(aminopropyl/methyl)silsesquioxane (PAMSQ) particles have been synthesized by
      a one-step hydrolytic co-condensation process using 3-aminopropyltriethoxysilane
      (APTES) and methyltrimethoxysilane (MTMS) as precursors in the presence of base
      catalyst in aqueous medium. The amino functionalities of the particles could be
      controlled by adjusting the organosilanes feed ratio. The compositions of the
      amino-functionalized polysilsesquioxanes were confirmed by FT-IR spectroscopy,
      solid-state (29)Si NMR spectroscopy, and elemental analysis. The strong
      adsorbability of Cu(II) and Pb(II) ions onto PAMSQ particles was systematically
      examined. The effect of adsorption time, initial metal ions concentration and pH
      of solutions was studied to optimize the metal ions adsorbability of PAMSQ
      particles. The kinetic studies indicated that the adsorption process well fits
      the pseudo-second-order kinetics. Adsorption phenomena appeared to follow
      Langmuir isotherm. The PAMSQ particles demonstrate the highest Cu(II) and Pb(II)
      adsorption capacity of 2.29 mmol/g and 1.31 mmol/g at an initial metal ions
      concentration of 20mM, respectively. The PAMSQ particles demonstrate a promising
      application in the removal of Cu(II) and Pb(II) ions from aqueous solutions.

PMID- 21945684
TI  - Pre-irradiation of anatase TiO2 particles with UV enhances their cytotoxic and
      genotoxic potential in human hepatoma HepG2 cells.
AB  - Titanium dioxide (TiO(2)) is active in the UV region of the light spectra and is
      used as a photocatalyst in numerous applications. Photo-activated anatase TiO(2)
      particles promote increased production of free radicals. This is a desirable
      property, although the potential toxicity of such photo-activated TiO(2)
      particles on exposure of humans and the environment remains unknown. Therefore,
      we studied whether pre-irradiation of TiO(2) particles with UV influences their
      cytotoxic and genotoxic potential. The TiO(2) particles, as TiO(2)-A (<25 nm) and
      TiO(2)-B (>100 nm), were UV pre-irradiated (24h) and tested for cytotoxic and
      genotoxic activities in human hepatoma HepG2 cells. Non-irradiated TiO(2)-A/B at
      1.0-250 MUg/ml did not reduce viability of HepG2 cells, nor induce significant
      increases in DNA strand breaks; only TiO(2)-A induced significant increases in
      oxidative DNA damage. After UV pre-irradiation, both TiO(2)-A and TiO(2)-B
      reduced cell viability and induced significant increases in DNA strand breaks and
      oxidative DNA damage. This is the first study that shows that UV pre-irradiation
      of anatase TiO(2) particles results in increased cytotoxic and genotoxic
      potential. This warrants further studies as it has important implications for
      environmental and human health risk assessment and preventive actions to limit
      human exposure.

PMID- 21945685
TI  - Magnetic loading of TiO2/SiO2/Fe3O4 nanoparticles on electrode surface for
      photoelectrocatalytic degradation of diclofenac.
AB  - A novel magnetic nanomaterials-loaded electrode developed for
      photoelectrocatalytic (PEC) treatment of pollutants was described. Prior to
      electrode fabrication, magnetic TiO(2)/SiO(2)/Fe(3)O(4) (TSF) nanoparticles were
      synthesized and characterized by X-ray diffraction (XRD), transmission electron
      microscopy (TEM) and FT-IR measurements. The nanoparticles were dispersed in
      ethanol and then immobilized on a graphite electrode surface with aid of magnet
      to obtain a TSF-loaded electrode with high photoelectrochemical activity. The
      performance of the TSF-loaded electrode was tested by comparing the PEC
      degradation of methylene blue in the presence and absence of magnet. The
      magnetically attached TSF electrode showed higher PEC degradation efficiency with
      desirable stability. Such a TSF-loaded electrode was applied to PEC degradation
      of diclofenac. After 45 min PEC treatment, 95.3% of diclofenac was degraded on
      the magnetically attached TSF electrode.

PMID- 21945686
TI  - Occurrence of metolachlor and trifluralin losses in the Save river agricultural
      catchment during floods.
AB  - Rising pesticide levels in streams draining intensively managed agricultural land
      have a detrimental effect on aquatic ecosystems and render water unfit for human
      consumption. The Soil and Water Assessment Tool (SWAT) was applied to simulate
      daily pesticide transfer at the outlet from an agriculturally intensive catchment
      of 1110 km(2) (Save river, south-western France). SWAT reliably simulated both
      dissolved and sorbed metolachlor and trifluralin loads and concentrations at the
      catchment outlet from 1998 to 2009. On average, 17 kg of metolachlor and 1 kg of
      trifluralin were exported at outlet each year, with annual rainfall variations
      considered. Surface runoff was identified as the preferred pathway for pesticide
      transfer, related to the good correlation between suspended sediment exportation
      and pesticide, in both soluble and sorbed phases. Pesticide exportation rates at
      catchment outlet were less than 0.1% of the applied amount. At outlet, SWAT
      hindcasted that (i) 61% of metolachlor and 52% of trifluralin were exported
      during high flows and (ii) metolachlor and trifluralin concentrations exceeded
      European drinking water standards of 0.1 MUg L(-1) for individual pesticides
      during 149 (3.6%) and 17 (0.4%) days of the 1998-2009 period respectively. SWAT
      was shown to be a promising tool for assessing large catchment river network
      pesticide contamination in the event of floods but further useful developments of
      pesticide transfers and partition coefficient processes would need to be
      investigated.

PMID- 21945687
TI  - A nanofiber functionalized with dithizone by co-electrospinning for lead (II)
      adsorption from aqueous media.
AB  - An electrospun nanofiber was utilized as a sorbent in packed fiber solid phase
      extraction (PFSPE) for selective separation and preconcentration of lead (II).
      The nanofiber had a polystyrene (PS) backbone, which was functionalized with
      dithizone (DZ) by co-electrospinning of a PS solution containing DZ. The
      nanofiber exhibited its performance in a cartridge prepared by packing 5mg of
      nanofiber. The nanofiber was characterized by a scanning electron microscope and
      IR spectra. The diameter of the nanofiber was less than 400 nm. After being
      activated by 2.0 mol L(-1) NaOH aqueous solution, the nanofiber quantitatively
      sorbed lead (II) at pH 8.5, and the metal ion could be desorbed from it by three
      times of elution with a small volume of 0.1 mol L(-1) HNO(3) aqueous solution.
      The breakthrough capacity was 16 MUg mg(-1). The nanofiber could be used for
      concentration of lead (II) from water and other aqueous media, such as plasma
      with stable recovery in a simple and convenient manner.

PMID- 21945688
TI  - Identification of porcine polycystic kidney disease 1 (PKD1) gene: molecular
      cloning, expression profile, and implication in disease model.
AB  - The polycystic kidney disease 1 (PKD1) gene, which accounts for ~85% of human
      autosomal dominant polycystic kidney disease (ADPKD) cases, has been extensively
      studied in human and mouse. Much information about the pathogenesis of and
      treatments for ADPKD has been gained from the use of mouse models. However,
      because mouse models pose some limitations, further studies in other model
      systems are needed to investigate the biological basis of ADPKD. The pig is
      regarded as an important biomedical model. Thus, we isolated a pig PKD1 homolog
      and characterized its cDNA sequence, genomic structure, expression profile,
      alternative splicing, methylation status, protein characteristics, and
      immunohistochemical features in both neonatal and adult pigs. The pig PKD1 cDNA
      is 14,209bp long and encodes a 4305-residue polypeptide. The genomic sequence of
      PKD1 is ~50kb with 46 exons. An alternative splice acceptor site was identified
      in intron 9. PKD1 is expressed in all tissues tested in both neonatal and adult
      pigs and exhibits a developmentally regulated expression pattern. Western
      blotting revealed that the molecular mass of polycystin-1 is ~460kDa, but its
      expression level is relatively low. Immunohistochemical study of the kidneys
      shows that polycystin-1 is mainly expressed in the tubular epithelia. Bisulfite
      methylation analysis of CpG islands in the promoter region does not show a direct
      correlation between methylation status and expression level among different
      tissues/cells. The cloning and characterization of pig PKD1 indicates that the
      pig and human genes are highly similar in length of genomic and cDNA sequences,
      genomic structure and context, expression patterns, conserved transcription
      factor binding sites, and the molecular mass of the encoded polycystin-1. These
      data support our current understanding of PKD1, and suggest that the pig is an
      ideal candidate for development of an ADPKD disease model.

PMID- 21945689
TI  - Molecular characterization of relatedness among colour variants of Asian Arowana
      (Scleropages formosus).
AB  - Morphological identification of fish taxa can sometimes prove difficult because
      phenotypic variation is either being affected by environmental factors,
      phenotypic characters are highly conserved or marker selection has been
      inappropriate. DNA based markers especially neutral mitochondrial DNA (mtDNA)
      have been used widely in recent times to provide better resolution of systematic
      relationships among vertebrate taxa. The Asian Arowana (Scleropages formosus) is
      a high value ornamental fish belonging to the family Osteoglossidae with a number
      of different colour variants distributed geographically across different
      locations around Southeast Asia. Systematic relationships among colour variants
      still remain unresolved. Partial sequences of the Cytochrome B (Cyt B) and DNA
      barcoding gene, Cytochrome C Oxidase I (COI) were used here to assess genetic
      relationships among colour variants and as a tool for molecular identification
      for differentiating among colour variants in this species. Results of the study
      show that in general, colour pattern shows no relationship with extent of COI or
      Cyt B mtDNA differentiation and so cannot be used to identify taxa. Partial
      sequences of the mtDNA genes were sufficient however, to identify S. formosus
      from a closely related species within the order Osteoglossidae.

PMID- 21945690
TI  - Sequence variations and two levels of MCT1 and CD147 expression in red blood
      cells and gluteus muscle of horses.
AB  - MCT1-CD147 complex is the prime lactate transporter in mammalian plasma
      membranes. In equine red blood cells (RBCs), activity of the complex and
      expression of MCT1 and CD147 is bimodal; high in 70% and low in 30%. We studied
      whether sequence variations contribute to the bimodal expression of MCT1 and
      CD147. Samples of blood and cremaster muscle were collected in connection of
      castration from 24 horses. Additional gluteus muscle samples were collected from
      15 Standardbreds of which seven were known to express low amounts of CD147 in
      RBCs. The cDNA of MCT1 and CD147 together with a promoter region of CD147 was
      sequenced. The amounts of MCT1 and CD147 expressed in RBC and muscle membranes
      were measured by Western blot and mRNA levels in muscles by qPCR. MCT1 and CD147
      were expressed in 20 castrates, and in four only were traces found. Sequence
      variations found in MCT1 were not linked to MCT1 expression. In CD147 linked
      heterozygous single nucleotide polymorphisms (SNPs) 389A>G (Met(125)Val) and
      990C>T (3'-UTR) were associated to low expression of CD147. Also a mutation
      168A>G (Ile(51)Val) in CD147 was associated to low MCT1 and CD147 expression. Low
      MCT1 and CD147 mRNA levels in gluteus were found in Standardbreds with low CD147
      expression in RBCs. The results suggest that sequence variations affect the
      expression level of CD147, but do not explain its bimodality. The levels of MCT1
      and CD147 mRNA correlated with the expression of CD147 and suggest that
      bimodality of their expression is regulated at transcriptional level.

PMID- 21945691
TI  - Reconstruction of flexor and extensor muscle activities from
      electroencephalography cortical currents.
AB  - The ability to reconstruct muscle activity time series from
      electroencephalography (EEG) may lead to drastic improvements in brain-machine
      interfaces (BMIs) by providing a means for realistic continuous reproduction of
      dexterous movements in human beings. However, it is considered difficult to
      isolate signals related to individual muscle activities from EEG because EEG
      sensors record a mixture of signals originating from many cortical regions. Here,
      we challenge this assumption by reconstructing agonist and antagonist muscle
      activities (i.e. filtered electromyography (EMG) signals) from EEG cortical
      currents estimated using a hierarchical Bayesian EEG inverse method. Results of 5
      volunteer subjects performing isometric right wrist flexion and extension tasks
      showed that individual muscle activity time series, as well as muscle activities
      at different force levels, were well reconstructed using EEG cortical currents
      and with significantly higher accuracy than when directly reconstructing from EEG
      sensor signals. Moreover, spatial distribution of weight values for
      reconstruction models revealed that highly contributing cortical sources to
      flexion and extension tasks were mutually exclusive, even though they were mapped
      onto the same cortical region. These results suggest that EEG sensor signals were
      reasonably isolated into cortical currents using the applied method and provide
      the first evidence that agonist and antagonist muscle activity time series can be
      reconstructed using EEG cortical currents.

PMID- 21945692
TI  - SUMA.
AB  - Surface-based brain imaging analysis offers the advantages of preserving the
      topology of cortical activation, increasing statistical power of group-level
      statistics, estimating cortical thickness, and visualizing with ease the pattern
      of activation across the whole cortex. SUMA is an open-source suite of programs
      for performing surface-based analysis and visualization. It was designed since
      its inception to allow for a fine control over the mapping between volume and
      surface domains, and for very fast and simultaneous display of multiple surface
      models and corresponding multitudes of datasets, all while maintaining a direct
      two-way link to volumetric data from which surface models and data originated.
      SUMA provides tools for performing spatial operations such as controlled
      smoothing, clustering, and interactive ROI drawing on folded surfaces in 3D, in
      addition to the various level-1 and level-2 FMRI statistics including FDR and FWE
      correction for multiple comparisons. In our contribution to this commemorative
      issue of Neuroimage we touch on the importance of surface-based analysis and
      provide a historic backdrop that motivated the creation of SUMA. We also
      highlight features that are particular to SUMA, notably the standardization
      procedure of meshes to greatly facilitate group-level analyses, and the ability
      to control SUMA's graphical interface from external programs making it possible
      to handle large collections of data with relative ease.

PMID- 21945693
TI  - Brain regions associated with moment-to-moment adjustments in control and stable
      task-set maintenance.
AB  - While there is some consensus that cognitive control involves both a capacity to
      rapidly adjust to unexpected challenges and a capacity to prospectively maintain
      task-sets over longer timescales, there is disagreement concerning the neural
      implementation of these capacities. Some accounts, for example, associate rapid
      adjustments in control with a network of lateral prefrontal and parietal cortices
      and task-set maintenance with a network of anterior cingulate and insular
      cortices. Other accounts propose almost the opposite associations. The present
      study compared these accounts by means of a hybrid fMRI design. Twenty-three
      right-handed adults were administered a conflict-adaptation paradigm in which the
      frequency of compatible trials, and therefore, demands on rapid adjustments and
      stable task-set maintenance, varied parametrically across conditions. Increased
      demands on moment-to-moment adjustments were associated with a profile of phasic
      activity in anterior cingulate cortex, anterior insula, and inferior parietal
      cortex. By contrast, increased demands on stable task-set maintenance were
      associated with increased sustained activity in medial superior frontal gyrus.
      Theoretical implications are discussed.

PMID- 21945695
TI  - Stability of resting fMRI interregional correlations analyzed in subject-native
      space: a one-year longitudinal study in healthy adults and premanifest
      Huntington's disease.
AB  - The pattern of interregional functional MRI correlations at rest is being
      actively considered as a potential noninvasive biomarker in multiple diseases.
      Before such methods can be used in clinical studies it is important to establish
      their usefulness in three ways. First, the long-term stability of resting
      correlation patterns should be characterized, but there have been very few such
      studies. Second, analysis of resting correlations should account for the unique
      neuroanatomy of each subject by taking measurements in native space and avoiding
      transformation of functional data to a standard volume space (e.g., Talairach
      Tournox or Montreal Neurological Institute atlases). Transformation to a standard
      volume space has been shown to variably influence the measurement of functional
      correlations, and this is a particular concern in diseases which may cause
      structural changes in the brain. Third, comparisons within the patient population
      of interest and comparisons between patients and age-matched controls, should
      demonstrate sensitivity to any disease-related disruption of resting functional
      correlations. Here we examine the test-retest stability of resting fMRI
      correlations over a period of one year in a group of healthy adults and in a
      group of cognitively intact individuals who are gene-positive for Huntington's
      disease. A recently-developed method is used to measure functional correlations
      in the native space of individual subjects. The utility of resting functional
      correlations as a biomarker in premanifest Huntington's disease is also
      investigated. Results in control and premanifest Huntington's populations were
      both highly consistent at the group level over one year. We thus show that when
      resting fMRI analysis is performed in native space (to reduce confounds in
      registration between subjects and groups) it has good long-term stability at the
      group level. Individual-subject level results were less consistent between visit
      1 and visit 2, suggesting further work is required before resting fMRI
      correlations can be useful diagnostically for individual patients. No significant
      effect of premanifest Huntington's disease on prespecified interregional fMRI
      correlations was observed relative to the control group using either baseline or
      longitudinal measures. Within the premanifest Huntington's group, though, there
      was evidence that decreased striatal functional correlations might be associated
      with disease severity, as gauged by estimated years to symptom onset or by
      striatal volume.

PMID- 21945696
TI  - Independent predictors of neuronal adaptation in human primary visual cortex
      measured with high-gamma activity.
AB  - Neuronal adaptation is defined as a reduced neural response to a repeated
      stimulus and can be demonstrated by reduced augmentation of event-related gamma
      activity. Several studies reported that variance in the degree of gamma
      augmentation could be explained by pre-stimulus low-frequency oscillations. Here,
      we measured the spatio-temporal characteristics of visually-driven amplitude
      modulations in human primary visual cortex using intracranial
      electrocorticography. We determined if inter-stimulus intervals or pre-stimulus
      oscillations independently predicted local neuronal adaptation measured with
      amplitude changes of high-gamma activity at 80-150 Hz. Participants were given
      repetitive photic stimuli with a flash duration of 20 MUs in each block; the
      inter-stimulus interval was set constant within each block but different (0.2,
      0.5, 1.0 or 2.0s) across blocks. Stimuli elicited augmentation of high-gamma
      activity in the occipital cortex at about 30 to 90 ms, and high-gamma
      augmentation was most prominent in the medial occipital region. High-gamma
      augmentation was subsequently followed by lingering beta augmentation at 20-30 Hz
      and high-gamma attenuation. Neuronal adaptation was demonstrated as a gradual
      reduction of high-gamma augmentation over trials. Multivariate analysis
      demonstrated that a larger number of prior stimuli, shorter inter-stimulus
      interval, and pre-stimulus high-gamma attenuation independently predicted a
      reduced high-gamma augmentation in a given trial, while pre-stimulus beta
      amplitude or delta phase had no significant predictive value. Association between
      pre-stimulus high-gamma attenuation and a reduced neural response suggests that
      high-gamma attenuation represents a refractory period. The local effects of pre
      stimulus beta augmentation and delta phase on neuronal adaptation may be modest
      in primary visual cortex.

PMID- 21945697
TI  - To wake or not to wake? The two-sided nature of the human K-complex.
AB  - Sleep fosters performance but likewise renders creatures insensitive to
      environmental threat. The brain balances between sleep promotion and protection
      during light sleep. One associated electrophysiological hallmark is the K-complex
      (KC), the sleep promoting versus arousal inducing role of which is under debate.
      We examined 37 subjects using EEG-combined fMRI and found KC-associated positive
      BOLD signal changes in subcortical (brainstem, thalamus), sensory and motor,
      midline and regions which form part of the default mode network, and negative
      changes in the anterior insula. Connectivity analysis revealed the primary
      auditory cortex as the first region to be influenced during the KC and that
      midline regions activated successively from front to back in association with the
      sleep protecting part of the KC. Our findings support thalamic involvement in KC
      mediation and an association of KCs with subcortical arousal mechanisms:
      activations in sensory areas suggest the existence of low level information
      processing during KC limited by anterior insula disengagement suggesting a two
      sided nature of the KC: it embodies an arousal with subsequent sleep-guarding
      counteraction that might on the one hand serve periodical monitoring of the
      environment with basic information processing and on the other hand protect the
      continuity of sleep and thus its restoring effect.

PMID- 21945698
TI  - Persistence of antibodies 3 years after booster vaccination of adults with
      combined acellular pertussis, diphtheria and tetanus toxoids vaccine.
AB  - The duration of protection after vaccination with reduced antigen content
      diphtheria, tetanus and acellular pertussis vaccines (Tdap) is not known. Long
      term post-vaccination serological data will help to improve understanding of the
      duration of humoral immunity and guide vaccination policy for the timing of
      repeat dose administration. The persistence of antibodies to Tdap antigens was
      measured 3 years after vaccination of adults 19-64 years of age with one of 2
      Tdap vaccines (Boostrix((r)), GlaxoSmithKline Biologicals; Tdap-B: or
      Adacel((r)), Sanofi Pasteur; Tdap-A). In both groups, geometric mean
      concentrations for antibodies to diphtheria, tetanus, and pertussis vaccine
      antigens were decreased at year 3 relative to levels observed 1 month and 1 year
      following vaccination, but remained higher than pre-vaccination levels.
      Seroprotection rates for diphtheria and tetanus remained high for both Tdap
      vaccines (for diphtheria, 96.9% and 97.8% for the Tdap-B and Tdap-A groups,
      respectively; for tetanus, 98.1% and 99.6%, respectively).

PMID- 21945699
TI  - Third International Summit: Current status of sleeve gastrectomy.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has been performed for morbid
      obesity in the past 10 years. LSG was originally intended as a first-stage
      procedure in high-risk patients but has become a stand-alone operation for many
      bariatric surgeons. Ongoing review is necessary regarding the durability of the
      weight loss, complications, and need for second-stage operations. METHODS: The
      first International Summit for LSG was held in October 2007, the second in March
      2009, and this third in December 2010. There were presentations by experts, and,
      to provide a consensus, a questionnaire was completed by 88 attendees who had >1
      year (mean 3.6 +/- 1.5, range 1-8) of experience with LSG. RESULTS: The results
      of the questionnaire were based on 19,605 LSGs performed within 3.6 +/- 1.5 years
      (228.8 +/- 275.0 LSGs/surgeon). LSG had been intended as the sole operation in
      86.4% of the cases; in these, a second-second stage became necessary in 2.2%. LSG
      was completed laparoscopically in 99.7% of the cases. The mean percentage of
      excess weight loss at 1, 2, 3, 4, and 5 years was 62.7%, 64.7%, 64.0%, 57.3%, and
      60.0%, respectively. The bougie size was 28-60F (mean 36F, 70% blunt tip).
      Resection began 1.5-7.0 cm (mean 4.8) proximal to the pylorus. Of the surgeons,
      67.1% reinforced the staple line, 57% with buttress material and 43% with
      oversewing. The respondents excised an estimated 92.9% +/- 8.0% (median 95.0%) of
      fundus (i.e., a tiny portion is maintained lateral to the angle of His). A drain
      is left by 57.6%, usually closed suction. High leaks occurred in 1.3% of cases
      (range 0-10%); lower leaks occurred in .5%. Intraluminal bleeding occurred in
      2.0% of cases. The mortality rate was .1% +/- .3%. CONCLUSION: According to the
      questionnaire, presentations, and debates, the weight loss and improvement in
      diabetes appear to be better than with laparoscopic adjustable gastric banding
      and on par with Roux-en-Y gastric bypass. High leaks are infrequent but
      problematic.

PMID- 21945700
TI  - Overexpression of (His)6-tagged human arginase I in Saccharomyces cerevisiae and
      enzyme purification using metal affinity chromatography.
AB  - Arginase (EC 3.5.3.1; L-arginine amidinohydrolase) is a key enzyme of the urea
      cycle that catalyses the conversion of arginine to ornithine and urea, which is
      the final cytosolic reaction of urea formation in the mammalian liver. The
      recombinant strain of the yeast Saccharomyces cerevisiae that is capable of
      overproducing arginase I (rhARG1) from human liver under the control of the
      efficient copper-inducible promoter CUP1, was constructed. The (His)(6)-tagged
      rhARG1 was purified in one step from the cell-free extract of the recombinant
      strain by metal-affinity chromatography with Ni-NTA agarose. The maximal specific
      activity of the 40-fold purified enzyme was 1600 MUmol min(-1) mg(-1) protein.

PMID- 21945702
TI  - Expression of active recombinant human gastric lipase in Nicotiana benthamiana
      using the CPMV-HT transient expression system.
AB  - Recombinant human gastric lipase (hGL) was transiently expressed in Nicotiana
      benthamiana leaves using the CPMV-HT expression system. Expression levels of up
      to 0.5mg recombinant hGL per gram of infiltrated leaf tissue were obtained.
      Proteins expressed from two hGL constructs, wild type (wt-hGL) and with a
      Histidine tag at its C terminal (hGL-His), were purified from leaf tissue using
      Immobilized Lectin Affinity chromatography and Immobilized Metal Affinity
      chromatography. Both variants were glycosylated, enzymatically active, and had an
      apparent molecular weight similar to native hGL (approx. 50kDa). The recombinant
      hGLs were stable under acidic conditions and in the presence of gastric pepsin.
      Moreover, as found with the naturally occurring enzyme, the activity of
      recombinant hGL on the short chain lipid, tributyrin, was higher than on long
      chain Intralipid 30% emulsion. The maximum specific activity measured on
      tributyrin was 310 U/mg of protein and the maximum yield was 193 U/g of
      infiltrated leaf tissue. These results show that transient expression in plants
      can be used to produce active hGL that could be efficiently purified using
      established techniques. The approach provides a means of generating large
      quantities of hGL that could be of use for a number of applications both in vitro
      and in vivo.

PMID- 21945701
TI  - Cloning, Escherichia coli expression, purification, characterization, and enzyme
      assay of the ribosomal protein S4 from wheat seedlings (Triticum vulgare).
AB  - S4 is a paradigm of ribosomal proteins involved in multifarious activities both
      within and outside the ribosome. For a detailed biochemical and structural
      investigations of eukaryotic S4, the wheat S4 gene has been cloned and expressed
      in Escherichia coli, and the protein purified to a high degree of homogeneity.
      The 285-residue recombinant protein containing an N-terminal His(6) tag along
      with fourteen additional residues derived from the cloning vector is
      characterized by a molecular mass of 31981.24 Da. The actual sequence of 265
      amino acids having a molecular mass of 29931 Da completely defines the primary
      structure of wheat S4. Homology modeling shows a bi-lobed protein topology
      arising from folding of the polypeptide into two domains, consistent with the
      fold topology of prokaryotic S4. The purified protein is stable and folded since
      it can be reversibly unfolded in guanidinium hydrochloride, and is capable of
      hydrolyzing cysteine protease-specific peptide-based fluorescence substrates,
      including Ac-DEVD-AFC (N-acetyl-Asp-Glu-Val-Asp-7-amino-4
      trifluoromethylcoumarin) and Z-FR-AMC (N-CBZ-Phe-Arg-aminomethylcoumarin).

PMID- 21945703
TI  - [Post-traumatic dysautonomic crises in intensive care unit: a French national
      assessment].
AB  - INTRODUCTION: The dysautonomic crises (DC) after traumatic brain injury are an
      unknown syndrome whereas the first case was described more than 50 years ago.
      This work aimed to collect their support modalities in French neuro-intensive
      cares units. MATERIAL AND METHODS: French medical doctors, working in neuro
      intensive care unit, were questioned by mail. The questionnaire developed point
      of prevalence, physiopathology, diagnosis, treatment, prognostic of DC and the
      existence of a support protocol in the department. RESULTS: There were 52 replies
      (40%) of 25 different hospitals. The DC were common or frequent for 77% of
      intensivists. The large majority (94%) reported a lack of knowledge about the
      physiopathology of the DC. The DC presented more often a therapeutic problem
      (28%) than a diagnostic problem (10%). The intensivists didn't know if the DC
      impacted on the prognostic of the patients (33%). The preferred treatment for the
      DC was an association of alpha/beta blockers and neuroleptics (38%). The more
      used preventive treatment was alpha/beta blockers (33%). Only two departments had
      a support protocol. CONCLUSION: Although DC were a common complication in neuro
      intensive care unit, their support seems mainly empirical.

PMID- 21945704
TI  - [Preoperative management to reduce morbidity and mortality of hip fracture].
AB  - Hip femur is extremely common in the elderly and is one of the most common
      reasons for admission in trauma care. The main reported causes of death after hip
      fracture were cardiovascular (29%), neurological (20%) and pulmonary. Large
      epidemiological studies have shown a relatively small decrease in mortality for
      20 years despite an active approach to medical and surgical management. Yet 57%
      of deaths occurring within 30 days post-surgery are preventable because they are
      not related to a pre-existing disease. Preoperative management to optimize these
      patients could help to reduce morbidity and mortality and is thus a crucial
      issue. The anesthesia consultation is used to evaluate the perioperative risk,
      treat pain, manage treatment and stabilize the patient. An operative delay of
      more than 48hours after admission increases mortality. This period should not be
      prolonged by unnecessary investigations that will not change the perioperative
      management. The preoperative period is a key moment because it allows to choose
      the anesthetic technique. Even if this choice is controversial, continuous spinal
      anesthesia (titrated) do not modify the cardiovascular and neurological
      physiological balance of these precarious patients.

PMID- 21945705
TI  - [Postoperative cognitive dysfunction (POCD): strategy of prevention, assessment
      and management].
AB  - The femoral neck fracture is a major cause of morbidity and mortality in the
      elderly. The etiology of cognitive impairment observed in this population of aged
      patient seems to be multifactorial. In the strategy of prevention, elderly
      patient must have the clearer information dealing with the postoperative
      cognitive dysfunction. This would reduce the incidence of POCD and some cognitive
      complaints, which often reflect the anxiety of the elderly patient facing the
      possibility of cognitive impairment. During the anaesthesia consultation, it
      seems important to assess the cognitive function of this elderly patient (like
      using neuropsycholgical scale as the MMSE) and to identify associated risk
      factors of cognitive dysfunction. The management of cognitive disorders should be
      multidisciplinary, the anesthesiologist being the main referent, in collaboration
      with the geriatrician and the surgeon. In the clinical setting of femoral neck
      fracture in the elderly, this multimodal management (pain, nutrition, functional
      rehabilitation to make these patients autonomous as quickly as possible), seems
      to improve the functional prognosis and to have the observed POCD decreased.

PMID- 21945706
TI  - College student reactions to health warning labels: sociodemographic and
      psychosocial factors related to perceived effectiveness of different approaches.
AB  - OBJECTIVE: To examine factors associated with perceiving different types of
      pictorial cigarette health warning labels as most effective in motivating smokers
      to quit or preventing smoking initiation among college students. METHOD: We
      administered an online survey to 24,055 students attending six Southeast colleges
      in Fall, 2010. We obtained complete data for the current analyses from 2600.
      RESULTS: Current smoking prevalence was 23.5%. The largest majority (78.6%)
      consistently rated gruesome images as most effective, 19.5% rated testimonial
      images as most effective, and only a small proportion rated either standard
      (1.6%) or human suffering images (0.3%) as most effective. Subsequent analyses
      focused on differences between those endorsing gruesome images or testimonials as
      most effective. Factors related to ranking testimonials versus gruesome images as
      most effective included being female (p<0.01), White (p<0.01), and nonsmokers
      (p=0.04), lower perceived smoking prevalence (p<0.01), and greater receptivity to
      laws/restrictions around smoking (p<0.01) and tobacco marketing (p=0.01). Among
      smokers, factors related to ranking testimonials as most effective versus
      gruesome images included being female (p=0.03), being White (p=0.03), higher
      autonomous motivation (p=0.03), and greater extrinsic self-efficacy (p=0.02).
      CONCLUSIONS: Understanding factors related to perceived effectiveness of
      different pictorial warnings among subpopulations should inform health warning
      labels released by the FDA.

PMID- 21945707
TI  - Bioinformatic characterization and gene expression pattern of apoptosis inhibitor
      from Macrobrachium rosenbergii challenged with infectious hypodermal and
      hematopoietic necrosis virus.
AB  - Apoptosis is genetically programmed cellular killing processes that execute
      unnecessary or infected cells. It plays an important role in embryogenesis,
      homeostasis, insect metamorphosis and immunity. Apoptosis inhibitor (MrIAP) was
      sequenced from the freshwater giant prawn Macrobrachium rosenbergii using
      Illumina Solexa Genome Analyzer Technique. MrIAP consisted of 1753 base pair
      nucleotides encoded 535 polypeptide with an estimated molecular mass of 60 kDa.
      MrIAP amino acid sequence contains IAP superfamily domain between 5 and 490. The
      deduced amino acid sequences of the MrIAP were aligned with the other IAP family
      members. The highest sequence similarity was observed in IAP-5 from ant
      Camponotus floridanus (67%) followed by IAP from body louse Pediculus humanus
      corporis (66%) and the lowest (62%) in IAP-5 isoform-5 from common chimpanzee Pan
      troglodytes and IAP-5 from Aedes aegypti. The IAP phylogenetic tree showed that
      MrIAP closely related to other arthropod blacklegged tick Ixodes scapularis,
      formed a sister group with IAP from a hemichordate acorn worm Saccoglossus
      kowalevskii and finally clustered together with IAPs from fish groups. The
      quantitative real time PCR analysis revealed that significantly (P < 0.05)
      highest expression was noticed in hepatopancreas and significantly (P < 0.05)
      lowest expression in pleopods. Based on the results of gene expression analysis,
      MrIAP mRNA transcription in M. rosenbergii challenged to infectious hypodermal
      and hematopoietic necrosis virus (IHHNV) was highly induced in hepatopancreas.
      The collective results of this study indicate that the MrIAP is an essential
      immune gene and influences the immune response against IHHNV infection in M.
      rosenbergii.

PMID- 21945708
TI  - Expression of FGF23/KLOTHO system in human vascular tissue.
AB  - BACKGROUND: Fibroblast growth factor (FGF)-23 levels have been associated with
      impaired vasoreactivity, increased arterial stiffness, and cardiovascular morbi
      mortality, whereas a protective function of KLOTHO against endothelial
      dysfunction has been reported. Since expression of the FGF23-KLOTHO system in
      human vascular tissue remains unproved, we aimed to study the expression of
      FGF23, FGF receptors (FGFR) and KLOTHO in human aorta. In addition, we analyzed
      the FGF23-KLOTHO expression in occlusive coronary thrombi. METHODS: Thoracic
      aorta specimens from 44 patients underwent elective cardiac surgery, and thrombus
      material from 2 patients with acute coronary syndrome (ACS), were tested for
      FGF23-KLOTHO system expression. RESULTS: Expression of KLOTHO (mean expression
      level 4.85 +/- 5.43, arbitrary units) and two of the three cognate FGFR (FGFR-1
      and -3) were detected and confirmed by RT-PCR, sequencing and qRT-PCR. KLOTHO
      expression was confirmed within occlusive coronary thrombi from patients with
      ACS. However, expression of FGF23 and FGFR4 was not observed. We also detected
      the aortic expression of membrane-anchored A Desintegrin and Metalloproteinases
      (ADAM)-17, the enzyme responsible for the shedding of KLOTHO from the cell
      surface, and the anti-inflammatory cytokine interleukin (IL)-10. Interestingly,
      in aortic samples there was a direct association between KLOTHO mRNA levels and
      those of ADAM-17 and IL-10 (r = 0.54, P<0.001; r = 0.51, P<0.01, respectively).
      CONCLUSIONS: Human vascular tissue expresses members of the FGF23-KLOTHO system,
      indicating that it can be a direct target organ for FGF23. In addition, KLOTHO
      expression is also detected in occlusive coronary thrombi. These findings suggest
      a putative role of FGF23-KLOTHO axis in human vascular pathophysiology and
      cardiovascular disease.

PMID- 21945709
TI  - The appropriate number of endpoints to keep validity for Cox proportional hazard
      analysis.

PMID- 21945711
TI  - Towards a unifying hypothesis for the pathogenesis of peripartum cardiomyopathy.

PMID- 21945710
TI  - Cardiac fibrosis and vascular remodeling are attenuated by metformin in obese
      rats.
AB  - BACKGROUND: Human obesity has been associated with alterations of vascular
      structure, especially in large and medium arteries, but the effects of insulin
      sensitizers are not well known. METHODS: Twenty-five male Wistar rats received
      subcutaneous injections of monosodium glutamate (MSG) or an equivalent volume of
      vehicle from the second to the sixth day after birth, At 16 weeks of age, five
      MSG rats started receiving an oral treatment with metformin (300 mg/kg) which was
      maintained for six weeks, composing five groups: control 16 weeks (CON-16), MSG
      16 weeks (MSG-16), control 22 weeks (CON-22), MSG 22 weeks (MSG-22), and MSG plus
      metformin 22 weeks (MET-22). Systolic blood pressure (BP) was verified weekly.
      The lumen diameter and media thickness, media cross-sectional area (CSA) and
      growth index of the intramyocardial arterioles were measured. Cardiac
      interstitial and perivascular collagen density were also evaluated. RESULTS:
      Systolic BP was significantly increased in the MSG-22 comparing to MSG-16 group.
      Insulin resistance was confirmed by HOMA-IR index and metformin-treated group
      presented reduction of insulin levels at week 22. The morphology analysis showed
      greater media-to-lumen ratio and CSA in the obese groups, which were reduced by
      the metformin treatment. Connective tissue deposition in the perivascular region
      of the left ventricle was significantly higher in the obese groups which was
      attenuated by metformin. CONCLUSIONS: Hypertrophic vascular remodeling and
      cardiac collagen deposition were significantly evident in MSG-induced obese rats.
      Metformin treatment was able to reduce insulin resistance and attenuated this
      adverse cardiac and vascular remodeling.

PMID- 21945712
TI  - Tricky mitral insufficiency during heart beating surgery.

PMID- 21945713
TI  - Selection for early surgery in asymptomatic mitral regurgitation: a Markov model.
AB  - BACKGROUND: Current guidelines propose mitral valve repair in asymptomatic
      chronic mitral regurgitation (MR) when the likelihood of repair is 90% or more.
      As this figure is not evidence-based, we sought whether the results of a decision
      analytic model could facilitate the selection between early surgery (ES) and
      watchful waiting (WW) based on current guidelines. METHODS: A Markov model was
      developed to reflect the anticipated health states in MR (pre-operative, post
      operative, post-complication and death). Risks and transitions were informed by
      the literature. Implications of the strategies for survival, quality-adjusted
      life years (QALYs), cost and cost-effectiveness were calculated from a US
      healthcare provider perspective. RESULTS: In the reference case (90% repair),
      QALY with ES was superior to WW (11.2 [0.4-21.3] vs 10.7 [95%CI: 1.0-21.3]) at an
      incremental cost-effectiveness of $54,659 ($45,030-$64,288) per QALY. Sensitivity
      analyses of health benefit showed the main variables influencing outcome were
      repair rate, operative mortality and risks of heart failure and death with
      medical management. At the registry repair rate (50%), outcomes of ES were worse
      than WW, and threshold analysis showed that a repair rate of 84% was required for
      ES to be superior. High medical risk (yearly heart failure risk 5.6 +/- 6.6% and
      mortality 2.5 +/- 4%) was the most favorable scenario for surgery; ES was more
      effective when mortality in the WW group was >3.5%/year. CONCLUSION: A Markov
      model might be used to guide the selection of asymptomatic patients for mitral
      repair, based on local variations in risk and complications as well as repair
      rate.

PMID- 21945714
TI  - Histological confirmation of hypersensitivity as a contributor to very-late
      coronary stent thrombosis.

PMID- 21945715
TI  - Effects of neuropeptide FF system on CB1 and CB2 receptors mediated
      antinociception in mice.
AB  - It has been demonstrated that opioid and cannabinoid receptor systems can produce
      similar signal transduction and behavioural effects. Neuropeptide FF (NPFF)
      belongs to an opioid-modulating peptide family. NPFF has been reported to play
      important roles in control of pain and analgesia through interactions with the
      opioid system. We were interested in whether the central and peripheral
      antinociception of cannabinoids could be influenced by supraspinal NPFF system.
      The present study examined the effects of NPFF and related peptides on the
      antinociceptive activities induced by the non-selective cannabinoid receptors
      agonist WIN55,212-2, given by supraspinal and intraplantar routes. In mice, the
      central and peripheral antinociception of WIN55,212-2 are mediated by cannabinoid
      CB(1) and CB(2) receptors, respectively. Interestingly, central administration of
      NPFF significantly reduced central and peripheral analgesia of cannabinoids in
      dose-dependent manners. In contrast, dNPA and NPVF (i.c.v.), two highly selective
      agonists for NPFF(2) and NPFF(1) receptors, dose-dependently augmented the
      antinociception caused by intracerebroventricular and intraplantar injection of
      WIN55,212-2. Additionally, pretreatment with the NPFF receptors selective
      antagonist RF9 (i.c.v.) markedly reduced the cannabinoid-modulating activities of
      NPFF and related peptides in nociceptive assays. These data provide the first
      evidence for a functional interaction between NPFF and cannabinoid systems,
      indicating that activation of central NPFF receptors interferes with cannabinoid
      mediated central and peripheral antinociception. Intriguingly, the present work
      may pave the way for a new strategy of using combination treatment of cannabinoid
      and NPFF agonists for pain management. This article is part of a Special Issue
      entitled 'Post-Traumatic Stress Disorder'.

PMID- 21945716
TI  - Curcumin exerts antinociceptive effects in a mouse model of neuropathic pain:
      descending monoamine system and opioid receptors are differentially involved.
AB  - Curcumin, a phenolic compound present in Curcuma longa, has been reported to
      exert antinociceptive effects in some animal models, but the mechanisms remain to
      be elucidated. This work aimed to investigate the antinociceptive action of
      curcumin on neuropathic pain and the underlying mechanism(s). Chronic
      constriction injury (CCI), a canonical animal model of neuropathic pain, was
      produced by loosely ligating the sciatic nerve in mice and von Frey hair or hot
      plate test was used to assess mechanical allodynia or thermal hyperalgesia (to
      heat), respectively. Chronic, but not acute, curcumin treatment (5, 15 or 45
      mg/kg, p.o., twice per day for three weeks) alleviated mechanical allodynia and
      thermal hyperalgesia in CCI mice, accompanied by increasing spinal monoamine (or
      metabolite) contents. Chemical ablation of descending noradrenaline (NA) by 6
      hydroxydopamine (6-OHDA), or depletion of descending serotonin by p
      chlorophenylalanine (PCPA), abolished curcumin's antinociceptive effect on
      mechanical allodynia or thermal hyperalgesia, respectively. The anti-allodynic
      action of curcumin on mechanical stimuli was totally blocked by chronic co
      treatment with the beta(2)-adrenoceptor antagonist ICI 118,551, or by acute co
      treatment with the delta-opioid receptor antagonist naltrindole. Meanwhile, co
      treatment with the 5-HT(1A) receptor antagonist WAY-100635 chronically, or with
      the irreversible mu-opioid receptor antangonist beta-funaltrexamine acutely,
      completely abrogated the anti-hyperalgesic action of curcumin on thermal stimuli.
      Collectively, these findings indicate that the descending monoamine system
      (coupled with spinal beta(2)-adrenoceptor and 5-HT(1A) receptor) is critical for
      the modality-specific antinociceptive effect of curcumin in neuropathic pain.
      Delta- and mu-opioid receptors are likely rendered as downstream targets,
      accordingly. This article is part of a Special Issue entitled 'Post-Traumatic
      Stress Disorder'.

PMID- 21945717
TI  - Modulatory effects of two novel agonists for serotonin receptor 7 on emotion,
      motivation and circadian rhythm profiles in mice.
AB  - Serotonin receptor 7, i.e. 5-HT(7) protein coded by Htr7 gene, was discovered in
      supra-chiasmatic nucleus (SCN) of the hypothalamus but is widespread in the
      forebrain. Studies have shown that this receptor is involved in learning/memory,
      regulation of mood and circadian rhythms. The modulatory effects of two novel
      agonists, LP-211 and LP-378, were assessed in male adult CD-1 mice with a battery
      of behavioral tests. Exp. 1 (Black/White Boxes, BWB: Adriani et al., 2009) and
      Exp. 2 (Dark/Light, D/L; Novelty-seeking, N-S) show: a) that LP-211
      administration (acutely, at a 0.25 mg/kg dose i.p.) increases locomotion and BWB
      exploration; b) that the time spent away from an aversive, lit chamber (i.e.,
      stress-induced anxiety) and in a new environment (i.e., novelty-induced
      curiosity) are both reduced. Sub-chronic LP-211 (at a 2.5 mg/kg dose i.p.)
      reveals a sensitization of locomotor-stimulant properties over 4-5 days. In Exp.
      3 (BWB), a three- to four-fold dosage (acutely, at 0.83 mg/kg i.p.) is needed
      with LP-378 to increase locomotion and BWB exploration. In Exp. 4, mice under
      constant-light conditions reveal the expected spontaneous lengthening (1.5 h per
      day) of circadian rhythms. A significant phase advance is induced by LP-211 (at a
      0.25 mg/kg dose i.p., administered around activity offset), with onset of
      activity taking place 6 h earlier than in controls. In summary, LP-211 is able to
      act consistently onto exploratory motivation, anxiety-related profiles, and
      spontaneous circadian rhythm. In the next future, agonist modulation of 5-HT(7)
      receptors might turn out to be beneficial for sleep and/or anxiety disorders.
      This article is part of a Special Issue entitled 'Post-Traumatic Stress
      Disorder'.

PMID- 21945718
TI  - Nocturia and quality of life: results from the Boston area community health
      survey.
AB  - BACKGROUND: Nocturia, a common complaint in aging men and women, is frequently
      cited as the cause of nocturnal awakenings leading to sleep loss, daytime
      fatigue, and reduced quality of life (QOL). OBJECTIVE: Investigate the
      association of nocturia with QOL and depressive symptoms among men and women.
      DESIGN, SETTING, AND PARTICIPANTS: A population-based epidemiologic survey of
      urologic symptoms among persons aged 30-79 yr. A multistage stratified cluster
      sample design was used to randomly sample 5503 residents of Boston, MA, USA.
      MEASUREMENTS: Nocturia was defined as a self-report of two or more voiding
      episodes nightly or having to get up to urinate more than once nightly "fairly
      often," "usually," or "almost always." QOL was assessed using the physical and
      mental health component scores of the 12-Item Short-Form Survey (SF-12).
      Depression was assessed using the Center for Epidemiological Studies Depression
      Scale. Multiple linear and logistic regression methods were used to model the
      nocturia and QOL association and to control for confounders. RESULTS AND
      LIMITATIONS: Nocturia was associated with decreased SF-12 scores for both the
      physical and mental health components after multivariate adjustment. Nocturia was
      also associated with increased odds of depressive symptoms (men: adjusted odds
      ratio [OR]: 2.79; 95% confidence interval [CI], 1.81-4.31; women: adjusted OR:
      1.80; 95% CI, 1.29-2.51). Among women who reported sleep interference due to
      urologic symptoms, nocturia was associated with a threefold increase in odds of
      depression. In this cross-sectional analysis, the temporal sequence of causality
      of the nocturia and depression association could not be assessed. CONCLUSIONS:
      Nocturia is associated with decreased QOL and with an increased prevalence of
      depressive symptoms in both men and women.

PMID- 21945720
TI  - alpha,beta-Unsaturated monoterpene acid glucose esters: structural diversity,
      bioactivities and functional roles.
AB  - The glycosylation of lipophilic small molecules produces many important plant
      secondary metabolites. The majority of these are O-glycosides with relatively
      fewer occurring as glucose esters of aromatic or aliphatic acids. In particular,
      monoterpene acid glucose esters have much lower structural diversity and
      distribution compared to monoterpene glycosides. Nevertheless, there have been
      over 20 monoterpene acid glucose esters described from trees in the genus
      Eucalyptus (Myrtaceae) in recent years, all based on oleuropeic acid,
      menthiafolic acid or both. Here we review all of the glucose esters containing
      these monoterpenoids identified in plants to date. Many of the compounds contain
      phenolic aglycones and all contain at least one alpha,beta-unsaturated carbonyl,
      affording a number of important potential therapeutic reactivities such as anti
      tumor promotion, carcinogenesis suppression, and anti-oxidant and anti
      inflammatory activities. Additional properties such as cytotoxicity, bitterness,
      and repellency are suggestive of a role in plant defence, but we also discuss
      their localization to the exterior of foliar secretory cavity lumina, and suggest
      they may also protect secretory cells from toxic terpenes housed within these
      structures. Finally we discuss how the use of a recently developed protocol to
      isolate secretory cavities in a functional state could be used in conjunction
      with systems biology approaches to help characterize their biosynthesis and roles
      in plants.

PMID- 21945719
TI  - Multiple events of fractures and cardiovascular and thromboembolic disease
      following prostate cancer diagnosis: results from the population-based PCBaSe
      Sweden.
AB  - BACKGROUND: To date, adverse events of prostate cancer (PCa) treatment have only
      been studied as a single event, and little is known about the risk of subsequent
      adverse events. OBJECTIVE: We assessed the frequency of multiple events
      (fractures, stroke, heart disease [HD], and thromboembolic disease [TED])
      following PCa diagnosis. DESIGN, SETTING, AND PARTICIPANTS: PCBaSe Sweden is
      based on the National Prostate Cancer Register (NPCR) that covers >96% of
      incident PCa cases in Sweden. MEASUREMENTS: We evaluated the number of events
      (fractures, stroke, HD, and TED) leading to hospitalisation recorded in the
      National Hospital Discharge Registry after PCa diagnosis and conducted
      multivariate age-adjusted Cox proportional hazards regression to estimate the
      risk of developing multiple events. RESULTS AND LIMITATIONS: Between 1997 and
      2007, 30 642 men received primary endocrine treatment, 26 432 curative treatment,
      and 19 526 surveillance: 75% had no event during follow-up, 17% had one event,
      and 9% had more than one event. The incidence of any event was 102 in 1000 person
      years. Men who already had experienced an event, particularly HD, before or after
      the date of PCa diagnosis were more likely to have multiple events afterwards.
      For example, the hazard ratio of developing a third event for those with two or
      more events of HD before PCa diagnosis was 1.40 (95% confidence interval, 1.28
      1.52) compared with those with no events of HD before PCa diagnosis. Events
      treated without hospitalisation were not included, so the number of adverse
      events is possibly underestimated. CONCLUSIONS: A third of PCa patients with an
      adverse event after treatment subsequently experienced another adverse event, but
      apart from history of HD or stroke before PCa diagnosis, no specific
      characteristics were found for these men. Thus PCa management needs to take into
      account the risk of adverse events in all PCa patients, especially those with a
      history of adverse events before PCa diagnosis.

PMID- 21945721
TI  - Phenylalanine derived cyanogenic diglucosides from Eucalyptus camphora and their
      abundances in relation to ontogeny and tissue type.
AB  - The cyanogenic glucoside profile of Eucalyptus camphora was investigated in the
      course of plant ontogeny. In addition to amygdalin, three phenylalanine-derived
      cyanogenic diglucosides characterized by unique linkage positions between the two
      glucose moieties were identified in E. camphora tissues. This is the first time
      that multiple cyanogenic diglucosides have been shown to co-occur in any plant
      species. Two of these cyanogenic glucosides have not previously been reported and
      are named eucalyptosin B and eucalyptosin C. Quantitative and qualitative
      differences in total cyanogenic glucoside content were observed across different
      stages of whole plant and tissue ontogeny, as well as within different tissue
      types. Seedlings of E. camphora produce only the cyanogenic monoglucoside
      prunasin, and genetically based variation was observed in the age at which
      seedlings initiate prunasin biosynthesis. Once initiated, total cyanogenic
      glucoside concentration increased throughout plant ontogeny with cyanogenic
      diglucoside production initiated in saplings and reaching a maximum in flower
      buds of adult trees. The role of multiple cyanogenic glucosides in E. camphora is
      unknown, but may include enhanced plant defense and/or a primary role in nitrogen
      storage and transport.

PMID- 21945722
TI  - Eggplant polyphenol oxidase multigene family: cloning, phylogeny, expression
      analyses and immunolocalization in response to wounding.
AB  - Though polyphenol oxidase (PPO) genes from tomato and potato have been
      extensively studied, information about PPO genes in eggplant (Solanum melongena)
      is lacking. The main objective of this study is to understand the structural and
      functional aspects of eggplant PPO genes. Six eggplant PPO genes (SmePPO1-6)
      cloned by RACE and genome walking were found to be intronless and correspond to
      eight eggplant unigenes. Comprehensive sequence analyses indicated that the
      eggplant PPO genes exhibit considerable variation in the transit peptide regions,
      copper-binding domains and UTRs, and fall into two distinct structural classes.
      Further, PPO gene members appear to exist in clusters on eggplant chromosome 8 as
      seen in the case of tomato and potato PPOs. During normal growth and development,
      SmePPO1 and 2 are expressed in roots, whereas the transcript levels of all the
      eggplant PPO genes vary considerably in leaves, flowers and fruits. SmePPO1 was
      expressed in Escherichia coli as a GST fusion protein, and immunoblot using
      rabbit polyclonal antiserum to GST-SmePPO1 detected a major protein band (~70
      kDa) and a minor band (~67 kDa) in eggplant fruit extract. Tissue printing
      indicated the predominant presence of PPO in the exocarp and the areas
      surrounding the seeds in the mesocarp of eggplant fruits. Immunolocalization of
      PPOs in eggplant infested with shoot-and-fruit borer revealed localization of the
      PPO at the site of infection in tender shoots and fruits, and further inside the
      mature tissues. The upregulation of eggplant PPO gene transcripts following
      mechanical injury shows that all the genes except SmePPO2 are induced in the
      fruit over 6h. On the contrary, the transcripts of SmePPO2 and PPO3 are not
      detectable in the stem, and expression seems to be prominent over a 2h period for
      SmePPO1 and SmePPO4-6. Our results show that eggplant PPO genes are structurally
      different, and are differentially expressed in various tissues of eggplant
      indicating their functional diversity.

PMID- 21945723
TI  - Mechanisms of cadmium induced genomic instability.
AB  - Cadmium is an ubiquitous environmental contaminant that represents hazard to
      humans and wildlife. It is found in the air, soil and water and, due to its
      extremely long half-life, accumulates in plants and animals. The main source of
      cadmium exposure for non-smoking human population is food. Cadmium is primarily
      toxic to the kidney, but has been also classified as carcinogenic to humans by
      several regulatory agencies. Current evidence suggests that exposure to cadmium
      induces genomic instability through complex and multifactorial mechanisms.
      Cadmium dose not induce direct DNA damage, however it induces increase in
      reactive oxygen species (ROS) formation, which in turn induce DNA damage and can
      also interfere with cell signalling. More important seems to be cadmium
      interaction with DNA repair mechanisms, cell cycle checkpoints and apoptosis as
      well as with epigenetic mechanisms of gene expression control. Cadmium mediated
      inhibition of DNA repair mechanisms and apoptosis leads to accumulation of cells
      with unrepaired DNA damage, which in turn increases the mutation rate and thus
      genomic instability. This increases the probability of developing not only cancer
      but also other diseases associated with genomic instability. In the in vitro
      experiments cadmium induced effects leading to genomic instability have been
      observed at low concentrations that were comparable to those observed in target
      organs and tissues of humans that were non-occupationally exposed to cadmium.
      Therefore, further studies aiming to clarify the relevance of these observations
      for human health risks due to cadmium exposure are needed.

PMID- 21945694
TI  - BEaST: brain extraction based on nonlocal segmentation technique.
AB  - Brain extraction is an important step in the analysis of brain images. The
      variability in brain morphology and the difference in intensity characteristics
      due to imaging sequences make the development of a general purpose brain
      extraction algorithm challenging. To address this issue, we propose a new robust
      method (BEaST) dedicated to produce consistent and accurate brain extraction.
      This method is based on nonlocal segmentation embedded in a multi-resolution
      framework. A library of 80 priors is semi-automatically constructed from the NIH
      sponsored MRI study of normal brain development, the International Consortium for
      Brain Mapping, and the Alzheimer's Disease Neuroimaging Initiative databases. In
      testing, a mean Dice similarity coefficient of 0.9834+/-0.0053 was obtained when
      performing leave-one-out cross validation selecting only 20 priors from the
      library. Validation using the online Segmentation Validation Engine resulted in a
      top ranking position with a mean Dice coefficient of 0.9781+/-0.0047. Robustness
      of BEaST is demonstrated on all baseline ADNI data, resulting in a very low
      failure rate. The segmentation accuracy of the method is better than two widely
      used publicly available methods and recent state-of-the-art hybrid approaches.
      BEaST provides results comparable to a recent label fusion approach, while being
      40 times faster and requiring a much smaller library of priors.

PMID- 21945725
TI  - Histopathology of renal failure after heart transplantation: a diverse spectrum.
AB  - BACKGROUND: Chronic kidney disease occurs frequently after heart transplantation
      and is associated with significant morbidity and mortality. Herein we describe
      the histopathology associated with renal failure in a cohort of heart transplant
      recipients. METHODS: Over a 4-year period all patients with an estimated GFR <30
      ml/min/1.73 m(2) or significant proteinuria were referred to the kidney
      transplant clinic for clinical evaluation. A percutaneous renal biopsy was
      performed as part of a standardized evaluation. RESULTS: Eighteen patients
      underwent renal biopsy 5.8 +/- 4.1 years after transplantation. Hypertension
      (88.9%), Type 2 diabetes (55.6%) and allograft vasculopathy (38.9%) were
      prevalent. All patients were receiving calcineurin inhibitors. Mean creatinine
      was 2.9 +/- 1.2 mg/dl with an estimated GFR 27.9 +/- 9.1 ml/min/1.73 m(2). Eight
      patients (44%) had proteinuria >1 g per 24 hours. The major histologic findings
      were nephrosclerosis plus diabetic glomerulopathy (50%), nephrosclerosis and
      focal segmental glomerulosclerosis (22.2%) and nephrosclerosis alone (22.2%). One
      patient had direct CNI toxicity consisting of nodular sub-adventitial hyalinosis.
      Eleven patients (61.1%) had glomerular disease and 11 patients (61.1%) had
      moderate or severe tubular atrophy. During follow-up, 5 patients (27.8%) started
      hemodialysis, 4 (22.2%) died, and 2 (11.1%) received a renal transplant.
      CONCLUSIONS: We observed diverse histologic patterns in this series of renal
      biopsies suggesting that chronic kidney disease after heart transplantation has a
      complex and varied pathologic basis. Further defining the renal injuries that
      precede heart transplantation and predispose to the progression of kidney disease
      after transplant may assist in treating this population.

PMID- 21945726
TI  - Centriolar satellites: busy orbits around the centrosome.
AB  - Since its first description by Theodor Boveri in 1888, the centrosome has been
      studied intensely, and it revealed detailed information about its structure,
      molecular composition and its various functions. The centrosome consists of two
      centrioles, which generally appear in electron microscopy as barrel-shaped
      structures usually composed of nine microtubule triplets. An amorphous mass of
      pericentriolar material surrounds the centrioles and accumulates many proteins
      important for the integrity and function of centrosomes, such as the gamma
      tubulin ring complex (gamma-TuRC) that mediates microtubule nucleation and
      capping. In animal somatic cells, the centrosome generally accounts for the major
      microtubule organizing center, and the duplicated pair of centrosomes determines
      the poles of the microtubule-based mitotic spindle. Despite detailed insights
      into the centrosome's structure and function, it has been a complete mystery
      until a few years ago how centrosomes duplicate and assemble. Moreover, it is
      still largely unclear if and how centrosomal proteins or protein complexes are
      exchanged, replaced or qualitatively altered. Previously identified cytoplasmic
      granules, named "pericentriolar" or "centriolar satellites", might fulfil such
      functions in protein targeting and exchange, and communication between the
      centrosomes and the cytoplasm. In this review, we summarize current knowledge
      about the structure, molecular composition and possible roles of the satellites
      that seem to surround the core of the centrosome in most animal cells.

PMID- 21945724
TI  - A food predictive cue must be attributed with incentive salience for it to induce
      c-fos mRNA expression in cortico-striatal-thalamic brain regions.
AB  - Cues associated with rewards acquire the ability to engage the same brain systems
      as rewards themselves. However, reward cues have multiple properties. For
      example, they not only act as predictors of reward capable of evoking conditional
      responses (CRs), but they may also acquire incentive motivational properties. As
      incentive stimuli they can evoke complex emotional and motivational states. Here
      we sought to determine whether the predictive value of a reward cue is sufficient
      to engage brain reward systems, or whether the cue must also be attributed with
      incentive salience. We took advantage of the fact that there are large individual
      differences in the extent to which reward cues are attributed with incentive
      salience. When a cue (conditional stimulus, CS) is paired with delivery of food
      (unconditional stimulus, US), the cue acquires the ability to evoke a CR in all
      rats; that is, it is equally predictive and supports learning the CS-US
      association in all. However, only in a subset of rats is the cue attributed with
      incentive salience, becoming an attractive and desirable incentive stimulus. We
      used in situ hybridization histochemistry to quantify the ability of a food cue
      to induce c-fos mRNA expression in rats that varied in the extent to which they
      attributed incentive salience to the cue. We found that a food cue induced c-fos
      mRNA in the orbitofrontal cortex, striatum (caudate and nucleus accumbens),
      thalamus (paraventricular, intermediodorsal and central medial nuclei), and
      lateral habenula, only in rats that attributed incentive salience to the cue.
      Furthermore, patterns of "connectivity" between these brain regions differed
      markedly between rats that did or did not attribute incentive salience to the
      food cue. These data suggest that the predictive value of a reward cue is not
      sufficient to engage brain reward systems-the cue must also be attributed with
      incentive salience.

PMID- 21945727
TI  - Restoration of complex V deficiency caused by a novel deletion in the human
      TMEM70 gene normalizes mitochondrial morphology.
AB  - We report a fragmented mitochondrial network and swollen and irregularly shaped
      mitochondria with partial to complete loss of the cristae in fibroblasts of a
      patient with a novel TMEM70 gene deletion, which could be completely restored by
      complementation of the TMEM70 genetic defect. Comparative genomics analysis
      predicted the topology of TMEM70 in the inner mitochondrial membrane, which could
      be confirmed by immunogold labeling experiments, and showed that the TMEM70 gene
      is not restricted to higher multi-cellular eukaryotes. This study demonstrates
      that the role of complex V in mitochondrial cristae morphology applies to human
      mitochondrial disease pathology.

PMID- 21945729
TI  - Comparative proteomics of spinal cords of rat fetuses with spina bifida aperta.
AB  - Neural tube defects (NTDs) are complex congenital anomalies of the central
      nervous system, with a prevalence of 5 per 10,000 worldwide. However, current
      therapeutics for NTDs are unsatisfactory. The neurological complications remain
      the main problem for therapy. Neurological dysfunction could result from the
      primary defect or injuries to the uncovered neural tissue in the uterus. However,
      the pathological changes in the uncovered neural tissue have not been described.
      Here, we present our comparative proteomics study of the spinal cord from rat
      fetuses with all-trans retinoic-acid-induced spina bifida aperta. Proteins from
      spinal cords were subjected to 2-D gel electrophoresis, then protein
      identification by mass spectrometry. We identified 13 proteins with differential
      expression between normal spinal cords and those with spina bifida aperta. These
      identified proteins were reported to be involved in signal transduction, cell
      adhesion and migration, protein folding and apoptosis. We confirmed 4 identified
      proteins by immunoblot analysis and assessed their mRNA levels by quantitative
      real-time PCR. This is the first comparative proteomics of spinal cords from rat
      fetuses with spina bifida aperta. We demonstrate protein alterations that reflect
      the pathological situation of the uncovered neural tissue, which may help improve
      the treatment of NTDs.

PMID- 21945728
TI  - iTRAQ-based quantitative secretome analysis of Phanerochaete chrysosporium.
AB  - The basidiomycete fungi such as Phanerochaete chrysosporium secrete large amount
      of hydrolytic and oxidative enzymes and degrade lignocellulosic biomass. The
      lignin depolymerizing proteins were extensively studied, but cellulose,
      hemicellulose and pectin hydrolyzing enzymes were poorly explored. In this study
      P. chrysosporium was grown in cellulose, lignin and mixture of cellulose and
      lignin, and secretory proteins were quantified by isobaric tag for relative and
      absolute quantitation (iTRAQ)-based quantitative proteomics using liquid
      chromatography tandem mass spectrometry (LC-MS/MS). An iTRAQ quantified 117
      enzymes comprising cellulose hydrolyzing endoglucanases, exoglucanases, beta
      glucosidases; hemicelluloses hydrolyzing xylanases, acetylxylan esterases,
      mannosidases, mannanases; pectin-degrading enzymes polygalacturonase,
      rhamnogalacturonase, arabinose and lignin degrading protein belonging to
      oxidoreductase family. Under cellulose and cellulose with lignin culture
      conditions, enzymes such as endoglucanases, exoglucanases, beta-glucosidases and
      cellobiose dehydrogenase were significantly upregulated and iTRAQ data suggested
      hydrolytic and oxidative cellulose degradation. When lignin was used as a major
      carbon source, enzymes such as copper radical oxidase, isoamyl oxidase,
      glutathione S-transferase, thioredoxin peroxidase, quinone oxidoreductase, aryl
      alcohol oxidase, pyranose 2-oxidase, aldehyde dehydrogenase, and alcohol
      dehydrogenase were expressed and significantly regulated. This study explored
      cellulose, hemicellulose, pectin and lignin degrading enzymes of P. chrysosporium
      that are valuable for lignocellulosic bioenergy.

PMID- 21945730
TI  - Differential immune response of rainbow trout (Oncorhynchus mykiss) at early
      developmental stages (larvae and fry) against the bacterial pathogen Yersinia
      ruckeri.
AB  - Innate immune factors play a crucial role in survival of young fish especially
      during early stages of life when adaptive immunity is not fully developed. In the
      present study, we investigated the immune response of rainbow trout (Oncorhynchus
      mykiss) larvae and fry at an early stage of development. We exposed 17 and 87
      degrees  days post hatch larvae and fry (152 and 1118 degree days post hatch;
      avg. wt. 70 and 770 mg, respectively) to the bacterial pathogen, Yersinia ruckeri
      for 4h by bath challenge. Samples were taken at 4, 24, 72 and 96 h post exposure
      for qPCR and immunohistochemical analyses to elucidate the immune response
      mounted by these young fish. Larvae showed no mortality although infected larvae
      at 48 h post exposure showed hyperaemia in the mouth region and inflammation on
      the dorsal side of the body. Gene expression studies showed an up-regulation of
      iNOS and IL-22 in infected larvae 24h post exposure but most of the investigated
      genes did not show any difference between infected and uninfected larvae.
      Immunohistochemical studies demonstrated a high expression of IgT molecules in
      gills and CD8 positive cells in thymus of both infected and uninfected larvae.
      Infection of rainbow trout fry with Y. ruckeri, in contrast, induced a cumulative
      mortality of 74%. A high expression of cytokines (IL-1beta, TNF-alpha, IL-22, IL
      8 and IL-10), acute phase proteins (SAA, hepcidin, transferrin and
      precerebellin), complement factors (C3, C5 and factor B), antimicrobial peptide
      (cathelicidin-2) and iNOS was found in infected fry when compared to the
      uninfected control. IgT molecules and mannose binding lectins in gills of both
      infected and uninfected fry were detected by immunohistochemistry. The study
      indicated that early life stages (yolk-sac larvae), merely up-regulate a few
      genes and suggests a limited capacity of larvae to mount an immune response by
      gene regulation at the transcriptional level. Based on the observed clearance of
      bacteria and lack of mortality it could be speculated that larvae may be covered
      by protective shield of different immune factors providing protection against
      broad range of pathogens. However, the increased susceptibility of older fry
      suggests that Y. ruckeri may utilize some of the immune elements to enter the
      naive fish. The up-regulation of iNOS and IL-22 in the infected larvae implicates
      an important role of these molecules in immune response at early developmental
      stages. A dense covering of surfaces of gill filaments by IgT antibody in the
      young fish suggest a role of this antibody as innate immune factor at early
      developmental stages.

PMID- 21945731
TI  - Measurement of 1- and 3-methylhistidine in human urine by ultra performance
      liquid chromatography-tandem mass spectrometry.
AB  - BACKGROUND: Determination of 1-methylhistidine (1-MH) and 3-methylhistidine (3
      MH) is important to monitor muscle protein catabolism. Here, an ultra performance
      liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for
      quantification of 1-MH and 3-MH in human urine is described. METHODS: Urine
      samples were prepared by dilution with water after addition of isotopic internal
      standard. The samples were chromatographed on a SB-aq (2.1*50 mm, 1.8 MUm) column
      with acetonitrile -0.1% formic acid in water (2:98, v/v) as mobile phase. Mass
      spectrometric detection was performed on a triple quadrupole mass spectrometer
      using positive electrospray ionization (ESI). 1-MH and 3-MH were monitored by the
      following transitions: 1-MH, m/z 170.1-> m/z 126.1; 3-MH, m/z 170.1-> m/z 124.1.
      RESULTS: For 1-MH and 3-MH, calibration curves were linear over the concentration
      range of 5-500 nmol/ml. The lower limit of quantification was 5 nmol/ml. The
      accuracy was within 85%-115% and precision was <15%. 1-MH and 3-MH were proved to
      be stable under different storage and processing conditions. In addition, the
      detection was independent of matrix effect. CONCLUSION: This rapid and specific
      UPLC/MS-MS method is suitable for the determination of urinary 1-MH and 3-MH.

PMID- 21945732
TI  - Development and clinical application of a LC-MS/MS method for simultaneous
      determination of various tyrosine kinase inhibitors in human plasma.
AB  - BACKGROUND: Increasing numbers of tyrosine kinase inhibitors (TKIs) were studied
      and approved for therapy of malignancies and other diseases. The aim of this
      study was to develop and validate a specific, simple and rapid quantification
      method for various TKIs in human plasma. METHODS: A simultaneous test for six
      TKIs (erlotinib, imatinib, lapatinib, nilotinib, sorafenib, sunitinib) was
      developed using liquid chromatography tandem mass spectrometry in a multiple
      reaction monitoring mode. After protein precipitation the specimens were applied
      to the HPLC system and separated using a gradient of acetonitrile containing 1%
      formic acid with 10 mM ammoniumformiate on an analytic RP-C18 column. RESULTS:
      The calibration range was 10-1000 ng/mL for sunitinib and 50-5000 ng/mL for the
      other TKIs with coefficients of determination >=0.99 for all analytes. The intra-
      and inter day coefficients of variation were <=15% and the chromatographic run
      time was 12 min. Plasma specimens were stable for measurement for at least 1 week
      at 4 degrees C. Clinical applications of the assay are exemplarily discussed.
      CONCLUSIONS: This novel high-throughput method is suitable for specific
      simultaneous determination of different TKIs in routine clinical practice.

PMID- 21945733
TI  - Matrix metalloproteinase-26, a novel MMP, is constitutively expressed in the
      human intervertebral disc in vivo and in vitro.
AB  - Matrix metalloproteinase (MMP) regulation and expression is important in the
      aging/degenerating human intervertebral disc. MMP-26 (also known as matrilysin-2
      or endometase) is a newly discovered MMP which degrades type IV collagen,
      fibronectin, fibrinogen, vitronectin, denatured collagen types I-IV, insulin-like
      growth factor binding protein 1, and activated pro-MMP-9. Our objective here was
      to determine if it is present in human disc tissue and cultured disc cells.
      Immunohistochemistry and microarray gene expression analyses were used to
      evaluate the presence of MMP-26 in human disc tissue from healthy and degenerated
      discs. Immunohistochemistry was also applied to human annulus cells cultured in a
      collagen sponge. Cellular and matrix localization of MMP-26 was identified in the
      outer and inner annulus and in the nucleus pulposus. Fewer cells showed
      localization in the inner vs. outer annulus, and localization was sparse in the
      nucleus. During in vitro culture of annulus cells, MMP-26 was also expressed.
      Molecular analyses showed significant downregulation of expression of MMP-26
      (p=0.03), and significant 9.8-fold upregulation of TGF-beta (p=0.01) in more
      degenerated discs vs. healthier discs. Findings document the first identification
      of MMP-26 in the disc at the molecular and protein levels. Results point to the
      potentially important role of MMP-26 in matrix modulation during disc health and
      degeneration.

PMID- 21945734
TI  - Calcium entry via ORAI1 regulates glioblastoma cell proliferation and apoptosis.
AB  - INTRODUCTION: Calcium entry plays a critical role in the proliferation and
      survival of certain tumors. Ca(2+) release activated Ca(2+) (CRAC) channels
      constitute one of the most important pathways for calcium entry especially that
      of store-operated calcium entry (SOCE). ORAI1 and stromal interaction molecule1
      (STIM1) are essential protein components of CRAC channels. In this study we
      tested the effect of inhibiting CRAC through ORAI1 and STIM1 on glioblastoma
      multiforme (GBM) tumor cell proliferation and survival. METHODS: Two glioblastoma
      cell lines, C6 (rat) and U251 (human), were used in the study. ORAI1 and STIM1
      expressions were examined using Western blot and immunohistochemistry. CRAC
      channel activity and its components were inhibited with ion channel blockers and
      using siRNA knockdown. Changes in intracellular calcium concentration were
      recorded using Fura-2 fluorescent calcium imaging. Cell proliferation and
      apoptosis were examined using MTS and TUNEL assays, respectively. RESULTS: CRAC
      blockers, such as SKF-96365 (1-[2-(4-methoxyphenyl)-2-[3-(4-methoxyphenyl)
      propoxy]ethyl-1H-imidazole), 2-aminoethoxydiphenyl borate (2-APB) and
      Diethylstilbestrol (DES), inhibited cell proliferations and SOCE in GBM cells.
      Knockdown of ORAI1 and STIM1 proteins using siRNA significantly inhibited C6 cell
      proliferation and SOCE compared with those in control cells, and a more
      significant effect was observed in cells with ORAI1 siRNA knockdown than that of
      STIM1-treated cells. Both CRAC blockers and siRNA treatments increased apoptosis
      in C-6 cells compared with control. CONCLUSION: Calcium entry via ORAI1 and CRAC
      channels are important for GBM proliferation and survival.

PMID- 21945735
TI  - A comparative evaluation of microarray slides as substrates for the development
      of protease assay biosensors.
AB  - The application of commercially available microarray slides as substrates for
      fluorogenic protease assays has been explored in terms of binding efficiency,
      stability, and activity. A fluorescent, biotinylated substrate for botulinum
      neurotoxin A (BoNTA) was attached via self-assembled monolayer of Streptavidin to
      amine-reactive aldehyde, epoxy, hydrogel, and polymer slides. Nexterion Slide
      P(r) was found to have optimal protein binding efficiency and stability of the
      slides examined. Addition of glycerol to the printing buffer improved spot
      morphology significantly and polyvinylpyrrolidone provided long-term stability,
      allowing chips to be stored for up to 1 month with good viability. Detection of a
      recombinant BoNTA light chain was then carried out at 37 degrees C and a sub
      lethal dose was detected in 2 hours.

PMID- 21945737
TI  - Effects of intravenous ibandronate injection on renal function in women with
      postmenopausal osteoporosis at high risk for renal disease--the DIVINE study.
AB  - The Designed for intravenous (IV) Ibandronate reNal safety Evaluation (DIVINE)
      study was a 1-year prospective, randomized, open label, multi-center study that
      evaluated the renal safety of quarterly (every 3 months) ibandronate IV injection
      given over 15-30s compared with infusion given over 15 min, and weekly oral
      alendronate, in women with postmenopausal osteoporosis (PMO) at increased risk
      for renal disease. Both injection and infusion of IV ibandronate showed
      comparable safety to alendronate, with only small changes in serum creatinine
      (sCr) for each treatment group, and AEs were generally comparable between groups.
      All three treatments had similar effects on renal function, measured by change in
      baseline of the glomerular filtration rate; the ibandronate IV injection group
      was noninferior to the ibandronate IV infusion and weekly oral alendronate groups
      at 9 months, with similar results at 1 year. The results of this study
      demonstrate the profile of IV ibandronate, which allows it to be dosed as an IV
      injection in the primary care setting without the need for an infusion, even in
      patients with pre-existing hypertension or diabetes mellitus.

PMID- 21945736
TI  - The effect of CTLA-4Ig, a CD28/B7 antagonist, on the lung inflammation and T cell
      subset profile during murine hypersensitivity pneumonitis.
AB  - Hypersensitivity pneumonitis (HP) is an inflammatory lung disease characterized
      by an influx of activated T cells to the lung, in which the CD28/B7 costimulatory
      signals are essential for the T cell activation and the outcome of the
      inflammatory response. In this study, we investigated the effect of the CD28/B7
      antagonist, CTLA-4Ig, on the lung inflammation and the T cell subset profile in
      experimental Saccharopolyspora recivirgula (SR)-induced HP. C57BL/6 mice were
      treated with SR or saline during two and three weeks and in addition of CTLA-4Ig
      was administrated after either the second or third week and mice were sacrificed
      seven days later. The extent of the lung inflammation was quantified by
      histopathology and the lung T cell subsets (Treg, Th17, gammadeltaT and NKT) were
      analyzed by flow cytometry. Mice treated with CTLA-4Ig showed a significant
      decrease in the extent of lung damage (p<0.05), and exhibited a decreased number
      of inflammatory cells in the bronchoalveolar lavage (BAL) with diminished CD4/CD8
      T cell ratio. Also, a significant increase in the percentage of lung gammadeltaT
      (p<0.01) and NKT (p<0.05) cells was observed in two weeks SR-treated mice with
      the administration of CTLA-4Ig/SR. At 3 weeks, SR-treated mice showed an
      increased percentage of regulatory T cells but no significantly differences were
      found in the percentage of Th17 cells when compared with CTLA-4Ig/SR-treated
      mice. Our findings suggest that the treatment with CTLA-4Ig affects the HP
      progression and the lung T cell subset kinetics in mice.

PMID- 21945738
TI  - Normalized volume of interest selection and measurement of bone volume in microCT
      scans.
AB  - Quantification of osteolytic lesions in bone is pivotal in the research of
      metastatic bone disease in small animal models. Osteolytic lesions are quantified
      using 2D X-ray photographs, which often neglects to take into account any changes
      in 3D structure. Furthermore, measurement errors are inadvertently introduced
      when a region of interest with predefined dimensions is used during MicroCT
      analysis. To study osteolytic processes, a normalized method of selecting a
      region of interest is required. Here we describe a new method to select volumes
      of interest in a normalized way regardless of curvature, fractures or
      dislocations within the bone. In addition, this method enables the user to
      visualize normalized cross sections in an exact 90 degrees  angle or along the
      longitudinal axis of bone, at any given point. As a result, the user can compare
      measurements of diameter, volume and structure between different bones in a
      normalized manner.

PMID- 21945739
TI  - Effect of carrier particle shape on dry powder inhaler performance.
AB  - The aim of this study was to characterise the aerosolisation properties of
      salbutamol sulphate (SS) from dry powder inhaler (DPI) formulations containing
      different carrier products. The difference in the elongation ratio (ER) of the
      different carriers was highlighted. Different set of carriers, namely commercial
      mannitol (CM), commercial lactose (CL), cooling crystallised mannitol (CCM),
      acetone crystallised mannitol (ACM) and ethanol crystallised mannitol (ECM) were
      used and inspected in terms of size, shape, density, crystal form, flowability,
      and in vitro aerosolisation performance using Multi Stage Liquid Impinger (MSLI)
      and Aerolizer inhaler device. Solid-state and morphological characterization
      showed that CM product was in pure beta-form having particles with smaller ER
      (CM: ER=1.62 +/- 0.04) whereas ACM and ECM mannitol particles were in pure alpha
      form with higher ER (ACM: ER=4.83 +/- 0.18, ECM: ER=5.89 +/- 0.19). CCM product
      crystallised as mixtures of beta-form and delta-form and showed the largest
      variability in terms of particle shape, size, and DPI performance. Linear
      relationships were established showing that carrier products with higher ER have
      smaller bulk density (D(b)), smaller tap density (D(t)), higher porosity (P), and
      poorer flow properties. In vitro aerosolisation assessments showed that the
      higher the ER of the carrier particles the greater the amounts of SS delivered to
      lower airway regions indicating enhanced DPI performance. Yet, DPI performance
      enhancement by increasing carrier ER reached a "limit" as increasing carrier ER
      from 4.83+/-0.18 (ACM) to 5.89+/-0.19 (ECM) did not significantly alter fine
      particle fraction (FPF) of SS. Also, carrier particles with higher ER were
      disadvantageous in terms of higher amounts of SS remained in inhaler device (drug
      loss) and deposited on throat. Linear relationship was established (r(2)=0.87)
      showing that the higher the carrier ER the lower the drug emission (EM) upon
      inhalation. Moreover, poorer flowability for carrier products with higher ER is
      disadvantageous in terms of DPI formulation dose metering and processing on
      handling scale. In conclusion, despite that using carrier particles with higher
      ER can considerably increase the amounts of drug delivered to lower airway
      regions; this enhancement is restricted to certain point. Also, other limitations
      should be taken into account including higher drug loss and poorer flowability.

PMID- 21945740
TI  - Characterisation and stability studies of a hydrophilic decapeptide in different
      adjuvant drug delivery systems: a comparative study of PLGA nanoparticles versus
      chitosan-dextran sulphate microparticles versus DOTAP-liposomes.
AB  - Poly[lactic-co-glycolide] (PLGA) nanoparticles, chitosan-dextran sulphate
      microparticles, and DOTAP-liposomes were prepared as vaccine adjuvants and drug
      carriers for a small hydrophilic model peptide, and their different physico
      chemical properties (size, PDI, zeta-potential, pH-value and peptide loading)
      were investigated. The model peptide's encapsulation efficiency (EE) in PLGA
      particles amounted to 15%, for DOTAP-liposomes to 20% and for chitosan particles
      up to 90%. The structural appearance of the particles was visualized by SEM and
      TEM. The stability of the aqueous formulations and the corresponding
      lyophilisates was monitored for 12 weeks (stored at T=2-8 degrees C). The freeze
      drying process and the addition of an appropriate cryoprotective agent (sucrose)
      proved to be essential for all carrier systems. As a result of this study, three
      different peptide-loaded drug delivery systems with different properties were
      successfully manufactured and showed sufficient product stability of their freeze
      dried formulations over 12 weeks of storage.

PMID- 21945741
TI  - In vitro-in vivo correlation and bioavailability studies of captopril from novel
      controlled release donut shaped tablet.
AB  - A controlled release formulation of captopril which was coated and fabricated
      into a donut shaped tablet formulation, was investigated in rabbit for
      pharmacokinetic and in vitro-in vivo correlation studies. Coated donut shaped
      tablets were prepared and in vitro release was studied in simulated gastric fluid
      at three different RPMs. New Zealand albino male rabbits have been used as animal
      model for in vivo study. A sensitive and simple HPLC method was developed for the
      determination of captopril content in rabbit plasma. In vitro release studies
      showed that release patterns followed zero order for around 4h. Single oral
      administration of coated donut shaped tablets in rabbit illustrated retained
      availability of captopril to the injected drug. Captopril content could pursue
      the same release pattern over the same time course in in vivo study. The in vivo
      in vitro correlation coefficients obtained from point-to-point analysis were
      greater than 99% between concentrations at certain time points obtained from
      release study in simulated gastric fluid at different RPMs and HPLC analysis of
      rabbit's plasma. From the in vitro-in vivo correlation prediction it was evident
      that the coated donut shaped tablet is a good device for controlled delivery of
      captopril.

PMID- 21945743
TI  - Reassessing the evidence relating smoking bans to heart disease.
AB  - Recent studies have compared rates of acute myocardial infarction before and
      after introducing smoking bans. Some meta-analyses report post-ban reductions up
      to 19%, implausibly large considering likely changes in smoking habits and
      passive smoke exposure. Our literature reassessment demonstrates major weaknesses
      in many studies and meta-analyses, including failure to consider data from
      control areas or existing trends in acute myocardial infarction rates, incorrect
      estimation of variability, and use in some meta-analyses of results for
      population subsets or estimates apparently unrelated to the data reported. We
      report meta-analyses using a consistent approach to derive estimates of the ban
      effect, taking account of time trends and control data, which indicate a much
      smaller reduction. Preferring national to regional estimates where available, we
      estimate a 5% reduction (95% CI 3-8%). Omitting estimates where trend adjustment
      was impossible, this becomes 2.7% (2.1-3.4%), consistent with reported declines
      of 2-3% in large national populations (England, France, Italy, USA). We discuss
      some limitations of these estimates. Further evidence is needed, possibly by
      analyzing national mortality data. Our findings highlight the need for a valid
      approach when estimating the effect of bans, and demonstrate major weaknesses in
      many previous publications.

PMID- 21945742
TI  - Effective reduction of the interleukin-1beta transcript in osteoarthritis-prone
      guinea pig chondrocytes via short hairpin RNA mediated RNA interference
      influences gene expression of mediators implicated in disease pathogenesis.
AB  - OBJECTIVE: To ascertain a viral vector-based short hairpin RNA (shRNA) capable of
      reducing the interleukin-1beta (IL-1beta) transcript in osteoarthritis (OA)-prone
      chondrocytes and detect corresponding changes in the expression patterns of
      several critical disease mediators. METHODS: Cultured chondrocytes from 2-month
      old Hartley guinea pigs were screened for reduction of the IL-1beta transcript
      following plasmid-based delivery of U6-driven shRNA sequences. A successful
      plasmid/shRNA knockdown combination was identified and used to construct an adeno
      associated virus serotype 5 (AAV5) vector for further evaluation. Relative real
      time reverse transcription polymerase chain reaction (RT-PCR) was used to
      quantify in vitro transcript changes of IL-1beta and an additional nine genes
      following transduction with this targeting knockdown vector. To validate in vitro
      findings, this AAV5 vector was injected into one knee, while either an equivalent
      volume of saline vehicle (three animals) or non-targeting control vector (three
      animals) were injected into opposite knees. Fold differences and subsequent
      percent gene expression levels relative to control groups were calculated using
      the comparative CT (2(-DeltaDeltaCT)) method. RESULTS: Statistically significant
      decreases in IL-1beta expression were achieved by the targeting knockdown vector
      relative to both the mock-transduced control and non-targeting vector control
      groups in vitro. Transcript levels of anabolic transforming growth factor-beta
      (TGF-beta) were significantly increased by use of this targeting knockdown
      vector. Transduction with this targeting AAV5 vector also significantly decreased
      the transcript levels of key inflammatory cytokines [tumor necrosis factor-alpha
      (TNF-alpha), IL-2, IL-8, and IL-12] and catabolic agents [matrix
      metalloproteinase (MMP)13, MMP2, interferon-gamma (IFN-gamma), and inducible
      nitrous oxide synthase (iNOS)] relative to both mock-transduced and non-targeting
      vector control groups. In vivo application of this targeting knockdown vector
      resulted in a >50% reduction (P=0.0045) or >90% (P=0.0001) of the IL-1beta
      transcript relative to vehicle-only or non-targeting vector control exposed
      cartilage, respectively. CONCLUSIONS: Successful reduction of the IL-1beta
      transcript was achieved via RNA interference (RNAi) techniques. Importantly, this
      alteration significantly influenced the transcript levels of several major
      players involved in OA pathogenesis in the direction of disease modification.
      Investigations to characterize additional gene expression changes influenced by
      targeting knockdown AAV5 vector-based diminution of the IL-1beta transcript in
      vivo are warranted.

PMID- 21945744
TI  - Nucleotide correlation based measure for identifying origin of replication in
      genomic sequences.
AB  - Computational prediction of the origin of replication is a challenging problem
      and of immense interest to biologists. Several methods have been proposed for
      identifying the replicon site for various classes of organisms. However, these
      methods have limited applicability since the replication mechanism is different
      in different organisms. We propose a correlation measure and show that it is
      correctly able to predict the origin of replication in most of the bacterial
      genomes. When applied to Methanocaldococcus jannaschii, Plasmodium falciparum
      apicoplast and Nicotiana tabacum plastid, this correlation based method is able
      to correctly predict the origin of replication whereas the generally used GC skew
      measure fails. Thus, this correlation based measure is a novel and promising tool
      for predicting the origin of replication in a wide class of organisms. This could
      have important implications in not only gaining a deeper understanding of the
      replication machinery in higher organisms, but also for drug discovery.

PMID- 21945745
TI  - Treatment of cornual heterotopic pregnancy via selective reduction without
      feticide drug.
AB  - STUDY OBJECTIVE: To treat heterotopic pregnancy with a minimally invasive
      procedure, absent a feticide drug. DESIGN: Retrospective study (Canadian
      Classification III). SETTING: University-affiliated hospital, center of
      reproductive medicine, department of obstetrics and gynecology, central south
      university, Changsha Hunan China. PATIENTS: A total of nine patients' diagnosed
      cornual heterotopic pregnancy resulted from assisted reproduction technology.
      Among nine, five patients selected the cornual embryo reduction. INTERVENTIONS:
      Cornual embryo reduction and preservation of intrauterine embryo were done under
      guidance of transvaginal ultrasonography at 4-6 weeks after embryo transfer. No
      drug was given. MEASUREMENTS: Safety of operative procedure and pregnancy
      outcome. MAIN RESULTS: All five patients who underwent selective embryo reduction
      has no intraoperative or postoperative complication, however 3 of them delivered
      healthy babies while two aborted. CONCLUSION: An early intervention should be
      carried in vital stable patients by means of puncturing and aspirating cornual
      heterotopic pregnancy under transvaginal ultrasound guidance.

PMID- 21945746
TI  - [Clinicopathological characteristics of male breast cancer: analysis of 25 cases
      at a single institution].
AB  - OBJECTIVE: To investigate general and clinicopathological characteristics of male
      breast cancer and analyzed the factors affecting the outcomes of the patients
      based on the data from a single institution. METHODS: Twenty-five male breast
      cancer patients treated at Sun Yet-sen University Cancer Center between January
      1, 2000 and April 30, 2011 were included into the study. The patients were
      followed up for 1 to 90 months with a median follow-up of 51 months. The general
      and clinicopathological characteristics including family history, age, smoking,
      alcohol drinking, site of tumor, location of tumor, histological type, estrogen
      receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor
      2 (HER-2), Ki-67, vascular endothelial growth factor (VEGF), P53 expression,
      neoadjuvant chemotherapy, surgery, adjuvant chemotherapy, adjuvant radiotherapy,
      adjuvant endocrine therapy, tumor size, lymph node status, distant metastasis and
      TNM stage were investigated by univariate analysis to evaluate the impact of
      these factors on patient survival. RESULTS: The 5-year survival rate was 66.5% in
      these patients. Neoadjuvant chemotherapy, tumor size, lymph node status, distant
      metastasis and TNM stage were significant predictors for the overall survival.
      Patients receiving adjuvant endocrine therapy tended to have a better overall
      survival, though this was not supported statistically (P=0.086). However,
      patients with neoadjuvant chemotherapy had a poorer overall survival than those
      without it (P=0.000). Patients in stages I and II had better overall survival
      than those in stages III and IV (P=0.000). CONCLUSION: The 5-year survival rate
      was 66.5% in these male breast cancer patients. Neoadjuvant chemotherapy, tumor
      size, lymph node status, distant metastasis and TNM stage are significant
      predictors of the overall patient survival.

PMID- 21945747
TI  - [PEG-mediated covalent binding of VEGF to decellularized aortic valves promotes
      adhesion and proliferation of endothelial progenitor cells].
AB  - OBJECTIVE: To improve the biological properties of decellularized aortic valves
      by polyethylene glycol (PEG)-mediated covalent incorporation of vascular
      endothelial growth factor (VEGF). METHODS: PEG crosslinking of decellularized
      aortic valves were completed via a Michael-type addition reaction, followed by
      covalent incorporation of VEGF through another Michael-type addition reaction
      between the unsaturated propylene acyl of PEG and the thiol groups on cysteine
      residues of VEGF. The effect of VEGF incorporation was evaluated by enzyme-linked
      immunosorbent assay (ELISA) and immune fluorescence assay. The endothelial
      progenitor cells (EPCs) were seeded on decellularized aortic valves with or
      without these modifications, and after 10 days of culture, the valves were
      examined for DNA content and by hematoxylin-eosin staining and scanning electron
      microscopy. RESULTS: Immune fluorescence and ELISA showed that the maximal VEGF
      incorporation on the decellularized aortic valve reached 908.94?0.27 pg. Compared
      with the unmodified valves and the valves with PEG crosslinking, decellularized
      aortic valves with covalent incorporation of VEGF significantly promoted the
      adhesion and proliferation of EPCs, which formed a confluent cell monolayer on
      the valve surface. CONCLUSIONS: PEG-mediated covalent incorporation of VEGF in
      the decellularized aortic valves improves the adhesion and proliferation of the
      seeded EPCs to facilitate the construction of tissue-engineered heart valves.

PMID- 21945749
TI  - [Stem cell characteristics and islet differentiation potential of human amniotic
      epithelial cells].
AB  - OBJECTIVE: To establish a method for isolating and culturing human amniotic
      epithelial cells (hAECs) in a serum-free medium and investigate their
      transdifferentiation ability into islet-like cells. METHODS: The culture
      condition of hAECs was optimized using DMEM with different supplements. The
      genetic stability of the tenth-passage cells was assessed by chromosome analysis
      and G-banding method. The stem cell characteristics of the cells were identified
      by examination of the surface markers using immunofluorescence methods. The
      endocrine-related genes and hormones of the cells were tested after induced
      differentiation into islet-like cells. RESULTS: The hAECs allow stable passaging
      in the presence of 10 ng epidermal growth factor (EGF) in the culture medium.
      After 10 passages, the cells maintained a normal karyotype and G-banding profile.
      The hAECs expressed many multi-potent stem cell markers, including SSEA4, TRA-1
      60, and TRA-1-81. After induced differentiation, the endocrine-related genes were
      expressed in the islet-like cells, including PDX1, ngn3, insulin and glucagon.
      Insulin secretion increased in the differentiated islet-like cells in response to
      high glucose exposure. CONCLUSION: We established a method for isolating and
      expanding the hAECs in a serum-free medium. hAECs possess stem cell
      characteristics and can be induced to differentiate into islet-like cells in
      vitro.

PMID- 21945748
TI  - [Tacrolimus alleviates acute liver graft rejection by inhibiting glucocorticoid
      induced tumor necrosis factor-related protein ligand in rats].
AB  - OBJECTIVE: To investigate the mechanism underlying the inhibitory effect of
      tacrolimus (FK506) against acute liver graft rejection. METHODS: Rat models of
      orthotopic liver transplantation were divided into 3 groups, namely the tolerance
      group with Brown Norway (BN) rats as the donors and Lewis rats as the recipients,
      rejection group with Lewis rats as donors and BN rats as recipients, and FK506
      group with the same donor-recipient pair as in the rejection group and FK506
      treatment. The recipients were sacrificed 7 days after the transplantation, and
      the hepatic histology, cytokine levels, and glucocorticoid-induced tumor necrosis
      factor-related protein ligand (GITRL) expression in the liver and Kupffer cells
      were observed and detected. RESULTS: Compared with the tolerance group, the
      rejection group showed increased GITRL expressions in the liver and Kupffer cells
      (P<0.05), which was significantly lowered by FK506 treatment (P<0.05). Acute
      liver graft rejection caused significantly elevated interferon-gamma (IFN-gamma)
      levels and decreased interleukin-10 (IL-10) levels in the plasma and Kupffer
      cells (P<0.05), and these changes were obviously attenuated by FK506 treatment
      (P<0.05). CONCLUSION: The effect of FK506 in suppressing acute liver graft
      rejection is probably associated with down-regulated GITRL expression in the
      liver and Kupffer cells.

PMID- 21945750
TI  - [Induced differentiation of endometrial stromal stem cells into osteoblast and
      chondroblasts].
AB  - OBJECTIVE: To investigate the capacity of human endometrial stromal stem cells
      for differentiation into osteoblasts and chondroblasts and their potential as
      seeding cells in bone tissue engineering. METHODS: Human endometrial stromal stem
      cells were obtained from hysterectomy tissues from 15 women during normal
      menstrual cycles and induced to differentiate into osteoblasts and chondroblasts.
      The differentiated cells were examined with cytochemistry. RESULTS: A population
      of endometrial stromal stem cells was successfully isolated from human
      endometrial tissue and showed stable proliferation in vitro. After treatment with
      osteoblast and chondroblast revulsant, the endometrial stromal stem cells
      differentiated towards osteoblasts were verified by positive staining with
      alizarin red and towards chondroblasts by positive staining with Alcian blue.
      CONCLUSION: Endometrial stromal stem cells obtained from human endometrial tissue
      with multilineage potential can differentiate into osteoblasts and chondroblasts
      in vitro, and may serve as candidate autogenous seeding cells for bone tissue
      engineering.

PMID- 21945752
TI  - [Prevalence of hypertension and glucose/lipid metabolism disorders in 4960
      inpatients with chronic obstructive pulmonary disease during 2000-2010].
AB  - OBJECTIVE: To study the prevalence of hypertension and glucose/lipid metabolism
      induced by chronic obstructive pulmonary disease (COPD) in hospitalized patients
      and their correlations to age and gender. METHODS: A retrospectively prevalence
      survey was conducted among the in-patients with COPD treated in General Hospital
      of PLA, Peking Union Medical College Hospital and Beijing Hospital between
      January 1st, 2000 and March 20th, 2010. RESULTS: A total of 4960 COPD patients
      were selected, including 3570 male and 1390 female patients with a mean age of
      72.2?10.4 years. Among these patients, hypertension had the highest prevalence
      (40.3%), followed by diabetes/impaired glucose tolerance (18.8%) and then by
      hyperlipidemia/fat protein metabolism (6.9%). The prevalence of
      hyperlipidemia/lipoprotein metabolism in the COPD patients over 80 years old
      decreased significantly with age. The prevalence of hypertension increased with
      age. In patients over 50 years old, the prevalence of hypertension was
      significantly higher in female than in male patients (P<0.05). The prevalence of
      diabetes/impaired glucose tolerance increased with age in male patients but
      decreased in female patients aged :80 years (P<0.05). Female patients in 60-69.9
      and 70-79.9 years groups had significantly higher incidence of diabetes/impaired
      glucose tolerance than male patients (P<0.05), but not at older ages. The
      incidence of hyperlipidemia/lipoprotein metabolism disorder increased with age in
      both male and female patients aged below 80 years (P<0.05), but in 60-69.9 and 70
      79.9 year groups, female patients had a significantly higher incidence than male
      patients (P<0.05); at the ages :80 years, the incidences was lowered in both
      women and men without a gender-specific differences (P>0.05). CONCLUSIONS: The
      data we obtained concerning the prevalence of hypertension and glucose/lipid
      metabolism disorder, age distribution, and gender characteristics of the COPD
      patients provide a clear target for secondary prevention of COPD.

PMID- 21945751
TI  - [SUMO-2/3 can covalently bind to progesterone receptor B to regulate its
      transcriptional activity].
AB  - OBJECTIVE: To investigate whether progesterone receptor B (PRB) can be sumoylated
      by SUMO-2/3 and the effect of sumoylation on PRB transcriptional activity.
      METHODS: SUMO-2/3 cDNA was amplified from MCF-7 cDNA and cloned into the
      eukaryotic expression vector pcDNA3-FLAG. The plasmid pXJ40-myc-PRB was
      cotransfected with pcDNA3FLAG-SUMO2, pcDNA3FLAG-SUMO3 or the mock control into
      293T cells, and PRB sumoylation was detected by immunoprecipitation and Western
      blotting. The effect of PRB sumoylation on its transcriptional activity was
      determined using reporter luciferase assay. RESULTS: pcDNA3FLAG-SUMO2 and
      pcDNA3FLAG-SUMO3 vectors were successfully constructed. SUMO-2/3 could bind
      covalently to PRB and increase its transcriptional dependent on the presence of
      progesterone. CONCLUSION: PRB can be sumoylated by SUMO-2/3 and its function is
      regulated by this modification.

PMID- 21945753
TI  - [Effect of metformin on apoptosis of renal cell carcinoma cells in vitro and its
      mechanisms].
AB  - OBJECTIVE: To evaluate the effect of metformin on the apoptosis of renal cell
      carcinoma (RCC) cells in vitro and its mechanisms. METHODS: Fluorescent
      microscopy and flow cytometry were used to examine the changes in the apoptosis
      of 786-O cells after metformin treatment. The possible signaling molecules
      involved in this process were analyzed by immunoblot analysis of AMP-activated
      protein kinase (AMPK) signaling and caspase 9. RESULTS: Metformin induced
      apoptosis and caspase 9 activation in 786-O cells in low-serum medium but not in
      normal-serum medium. Metformin also induced AMPK activation in 786-O cells, but
      this activation was not associated with the cell proliferation inhibition or
      apoptosis-inducing effect of metformin. CONCLUSION: Metformin can induce
      apoptosis of RCC cells in vitro, suggesting its potential as a therapeutic agent
      for RCC.

PMID- 21945754
TI  - [Development of a time-resolved fluoroimmunoassay for detecting S1 subunit of
      pertussis toxin and its application].
AB  - OBJECTIVE: To develop a time-resolved fluoroimmunoassay (TRFIA) for detection of
      pertussis toxin (PT) S1 subunit for quality control of human PT vaccine. METHODS:
      A double antibody sandwich one-step method was used to establish the TRFIA for
      detecting PT S1 subunit in the vaccine. RESULTS: The sensitivity of c peptide
      analysis reached 2.5 ng/ml without cross-reactions with other antigens. This
      assay could be used in detecting S1 subunit in the vaccine. CONCLUSION: The TRFIA
      for detecting PT S1 subunit is simple, sensitive and rapid for quality control of
      the PT vaccine.

PMID- 21945755
TI  - [Touchdown PCR and overlap extension PCR for generating CD133(+) cancer stem cell
      selective adenovirus vector].
AB  - OBJECTIVE: To construct a replication-incompetent adenovirus vector targeting
      cancer stem cells by modified touchdown PCR and overlap extension PCR and
      investigate its infection efficiency in CD133(+) SW480 cells in vitro. METHODS:
      The two portions of the fiber gene encoding the Ad5 fiber knob domain with the HI
      loop deleted were amplified using two pairs of designed primers and then linked
      by overlap extension PCR. The product obtained was identified by sequencing and
      inserted into prokaryotic expression vector pEGFP-N1. The product, pEGFP-N1
      KNOBdeltaHI, contained a unique EcoRV restriction site in the deleted portion of
      the sequence encoding the HI loop. The gene sequences of the adenovirus fiber
      were amplified using both common PCR and overlap extension PCR, then identified
      by sequencing and inserted into pNEB193, resulting in pNEB-F5. CD133(+) SW480
      cells were infected with the generated adenovirus vectors Ad5-GFP and Ad5FHI-GFP
      to investigate the infection efficiency using fluorescent microscope. RESULTS:
      The target fragments of expected sizes were amplified by touchdown PCR and
      overlap extension PCR, but not by common PCR. Ad5FHI-GFP showed a higher
      infection efficiency than Ad5-GFP in CD133(+) SW480 cells. CONCLUSION: Compared
      with common PCR, touchdown PCR and overlap extension PCR can significantly
      improve the specificity and efficiency of the PCR products for constructing
      CD133(+) cancer stem cell-selective adenovirus type 5 vector, which provides
      carriers for tumor-targeted gene therapy.

PMID- 21945756
TI  - [Role of oxidative stress and thioredoxin in gastric cancer].
AB  - OBJECTIVE: To explore the role of oxidative stress and the antioxidant protein
      thioredoxin in the tumorigenesis and progression of gastric cancer. METHODS: The
      plasma levels of adenosine deaminase (ADA), glutathione peroxidase (GPX),
      superoxide dismutase (SOD), and advanced oxidation protein products (AOPP) were
      determined by colorimetry, and the plasma levels of thioredoxin were determined
      by enzyme-linked immunosorbent assay (ELISA) in 48 gastric cancer patients and 30
      healthy subjects. RT-PCR assay was employed to examine the expression levels of
      thioredoxin mRNA in the tissue samples of the patients. RESULTS: Compared with
      the healthy controls, patients with gastric cancer had significantly increased
      plasma levels of ADA and AOPP (P<0.05), decreased plasma GPX level (P<0.05), and
      similar plasma SOD levels. The plasma levels of thioredoxin were significantly
      higher in patients with gastric cancer than in the healthy controls (P<0.05).
      Thioredoxin levels was not associated with gender, age, degree of tumor cell
      differentiation, invasion depth, or lymph node metastasis (P>0.05), but was
      correlated to distant tumor metastasis (P<0.05). The expression of Trx mRNA was
      significantly higher in gastric carcinoma than in normal gastric tissue (P<0.05).
      CONCLUSION: Gastric cancer patients have high levels of oxidative stress and
      thioredoxin expression, and the latter is related to distant metastasis of the
      tumor.

PMID- 21945757
TI  - [Development of a hydrophilic anti-fogging agent for nasal endoscopy].
AB  - OBJECTIVE: To develop a transparent, non-toxic, non-irritating anti-fogging agent
      with long-lasting effect for nasal endoscopy. METHODS: The anti-fogging agent was
      prepared by mixing ethanol, propylene glycol, polyoxyethylene lauryl ether,
      sodium dodecyl sulfate, polyethylene glycol 400 and deionized water at different
      proportions based on an orthogonal test design. Twenty-seven test samples of the
      anti-fogging agents were obtained, which were colorless, transparent, and non
      irritating, with a pH value of 7-8. Storz00 nasal endoscopy and its imaging
      system were used to test the anti-fogging time of the 27 samples, and each agent
      was tested for 3 times with medical Seoul iodine and 95% ethanol as control.
      RESULTS: The optimal composition of the anti-fogging agent was 20% ethanol, 10%
      propylene glycol, 20% polyoxyethylene lauryl ether, 4% sodium dodecyl sulfate, 4%
      polyethylene glycol, 42% deionized water. The anti-fogging time of this agent
      reached 15 min, significantly longer than that of medical Seoul iodine (4 min)
      and 95% ethanol (18 s). CONCLUSION: This anti-fogging agent for nasal endoscopes
      is colorless and safe and has a long anti-fogging time by forming a homogenous
      transparent membrane over the endoscopic lens.

PMID- 21945758
TI  - [Effect of early intervention with rhein on islet function in db/db mice].
AB  - OBJECTIVE: To investigate the hypoglycemic action of rhein (4,5
      dihydroxyanthraquinone-2-carboxylic acid), one of the anthraquinone derivatives
      isolated from rhubarb, and study its effects on pancreatic beta-cells in db/db
      mice. METHODS: Thirty 4-week-old db/db mice were randomized for an 8-week
      treatment with intragastric administration of rhein (120 mg/kg, n=15) or placebo
      (1% natrium cellulose solution, n=15). After the treatment, intraperitoneal
      glucose tolerance test (IPGTT) was performed and the area under curve (AUC) of
      insulin levels in IPGTT was calculated to evaluate insulin secretory function.
      The AUC(INS0-30) was calculated to evaluate the early-phase insulin secretion.
      Immunohistochemical staining for insulin was performed to estimate the beta-cell
      mass, and beta-cell apoptosis was detected using TUNEL assay. RESULTS: Compared
      with the control group, rhein-treated group showed significantly reduced blood
      glucose concentrations at 0, 30, 60 and 120 min after glucose load with
      significantly higher insulin levels at 30, 60 and 120 min. The early-phase
      insulin secretion was also obviously increased. The beta-cell mass was obviously
      rescued by the 8-week treatment with rhein, which also notably improved the
      staining intensity of insulin and suppressed beta-cell apoptosis compared with
      the control. CONCLUSIONS: Early rhein treatment significantly improves glucose
      tolerance by restoring the early-phase insulin secretion in db/db mice and
      inhibiting the apoptosis of the beta-cells, suggesting the potential of rhein as
      a novel therapeutic agent for type 2 diabetes.

PMID- 21945759
TI  - [Protective effect of limited fluid resuscitation against intestinal ischemia
      reperfusion injury in postpartum rabbits with uncontrolled hemorrhagic shock].
AB  - OBJECTIVE: To investigate the protective effect of limited fluid resuscitation
      against intestinal ischemia- reperfusion injury in postpartum rabbits with severe
      uncontrolled obstetrical hemorrhagic shock. METHODS: Twenty- four postpartum
      rabbits were randomly assigned into sham shock group (group P), shock group
      without interventions (group P0), conventional fluid resuscitation group (group
      PNL), and limited fluid resuscitation group (group PLH), and the model of severe
      uncontrolled hemorrhagic shock was established in the latter 3 groups. The
      rabbits were sacrificed 4 h later, and SOD activity and MDA content in the
      intestinal mucosa and the degree of injury to the intestinal mucosa were
      observed. RESULTS: Ischemia-reperfusion injury of the intestine due to
      uncontrolled hemorrhagic shock resulted in decreased SOD activity and increased
      MDA content. The MDA content was significantly lower and SOD activity was
      significantly higher in group PLH than in group PNL (P<0.05), and the intestinal
      mucosal tissue morphology and intestinal mucosa barrier lesion increased in group
      PLH. CONCLUSION: Initial limited fluid  resuscitation can relieve intestinal
      ischemia-reperfusion injury in postpartum rabbits with severe uncontrolled
      obstetrical hemorrhagic shock.

PMID- 21945760
TI  - [Therapeutic effects of bone marrow transplantation on ovarian injury in mice].
AB  - OBJECTIVE: To evaluate the therapeutic effects of bone marrow transplantation
      (BMT) on ovarian injury induced by chemotherapy in mice. METHODS: Forty-eight
      mice were randomized equally into normal control group (A), cyclophosphamide and
      BMT group (B), and cyclophosphamide group (C). The mice in groups B and C were
      treated with intraperitoneal injection of cyclophosphamide at the daily dose of
      150 mg/kg for 3 consecutive days, and allogeneic bone marrow cell transplantation
      was performed in group B. The ovary coefficient and the amount of follicles were
      compared to evaluate the function of ovaries. For cell tracking, the bone marrow
      cells were labeled with Hoechst 33342 and detected through fluorescence
      microscope after transplantation. RESULTS: On days 21 and 50 after
      cyclophosphamide treatment, the ovary coefficient and the amount of follicles
      were significantly lowered in groups B and C (P<0.05), but the reduction was
      obviously ameliorated in group B (P<0.05). Cell tracking showed the presence of
      the donor bone marrow cells in the ovaries of the recipients mice after BMT.
      CONCLUSION: BMT can improve the ovarian function impaired by chemotherapy in
      mice.

PMID- 21945761
TI  - [Expressions of RANK, RANKL, and osteoprotegerin in male rats at different ages].
AB  - OBJECTIVE: To investigate the expression of receptor activator of nuclear factor
      kappaB (RANK), its ligand RANKL, and osteoprotegerin, and observe the effects of
      alphaD3 on their expressions in male rats at different ages. METHODS: Wistar rats
      at 6 weeks, 6 months, and 24 months (n=15) were examined for mRNA expressions of
      RANK/RANKL and osteoprotegerin in the left proximal femur using RT-PCR and for
      their protein expressions in the right femur using immunohistochemistry.
      RANK/RANKL and osteoprotegerin expressions were also detected in another 15 rats
      aged 24 months following intragastric administration of 0.05 ug/kg alphaD3 (3
      times a week for 10 weeks). RESULTS: Compared with 6-week-old rats, 6-month- and
      24-month-old rats showed a 6.2-fold and 7.3-fold increase of RANKL mRNA
      expression, respectively (P<0.05), and osteoprotegerin mRNA levels increased
      slightly with age. alphaD3 treatment resulted in significantly increased
      expression of RANK in 24-month-old rats with a lowered RANKL/osteoprotegerin
      ratio. RANKL and osteoprotegerin were co-localized in the osteoblasts and
      chondrocytes. alphaD3 treatment also caused an increased expression of
      osteoprotegerin mRNA in 24-month-old rats. CONCLUSION: The age-related increase
      of the ratio of RANKL/osteoprotegerin mRNA promotes osteoclast activity and bone
      turnover. alphaD3 has favorable effect on osteogenesis and suppress bone
      absorption in the femur possibly by reducing RANK expression and lowering
      RANKL/osteoprotegerin ratio.

PMID- 21945762
TI  - [Effect of willed movement therapy on GFAP and SYP expression in rats with
      cerebral ischemia-reperfusion].
AB  - OBJECTIVE: To determine the effect of willed movement on the expression of glial
      fibrillary acidic protein (GFAP) and synaptophysin (SYP) in adult rats with
      cerebral ischemia-reperfusion, and explore the mechanism of willed movement in
      promoting nerve repair and regeneration. METHODS: Adult rat models of cerebral
      ischemia-reperfusion injury were established by middle cerebral artery occlusion
      (MCAO) for 2 h followed by a 24-h reperfusion. The models were then divided
      randomly into 3 groups, namely the model group, environmental modification (EM)
      group, and willed movement (WM) group. In each group, neurological deficits were
      evaluated at 3, 7 and 15 days after reperfusion. Immunohistochemistry and
      immunofluorescence assay were employed to examine the expression of GFAP and SYP
      in the brain tissue near the ischemic foci. RESULTS: The rats in WM group showed
      lessened neurological deficits at 15 days and lowered expression of GFAP and SYP
      at 7 and 15 days after reperfusion compared with the model and EM groups
      (P<0.05). No significant difference was found in the expression of GFAP or SYP
      between the model group and EM group at any time points. CONCLUSION: Willed
      movement can promote the functional recovery of neurological deficits following
      cerebral ischemia-reperfusion probably in relation to enhanced GFAP and SYP
      expressions in the ischemic brain tissues.

PMID- 21945763
TI  - [Metabolic footprint in conditioned culture medium of placental explants: a
      comparison between early-onset and late-onset severe preeclampsia].
AB  - OBJECTIVE: To explore the differences of metabolic footprint in the conditioned
      culture medium of placental explants between early-onset and late-onset severe
      preeclampsia. METHODS: In 13 cases of early-onset severe preeclampsia and 14
      cases of late-onset severe preeclampsia, the placentas were sampled at the
      surface of the maternal placenta. High performance liquid chromatography-mass
      spectrometry (HPLC-MS) was used to determine the differences in the metabolites
      in the conditioned culture medium of the placental villous explants cultured in
      6% atmospheric O(2) for 96 h. Standard samples were used to establish the
      tryptophan and kynurenine chromatography library by HPLC-MS to analyze the
      concentration of tryptophan and kynurenine in the conditioned culture medium.
      RESULTS: Thirty-six metabolites showed statistically significant differences
      between early-onset and late-onset severe preeclampsia (P<0.05). The
      concentration of kynurenine was significantly higher in early-onset severe
      preeclampsia than in late-onset severe preeclampsia (P<0.05). CONCLUSION: Early
      onset and late-onset severe preeclampsia may have different pathogeneses. By
      detecting the concentration of metabolites, metabolomic strategies provide a new
      means for predicting the onset time of severe preeclampsia.

PMID- 21945764
TI  - [Expressions of MACC1, HGF, and C-met protein in epithelial ovarian cancer and
      their significance].
AB  - OBJECTIVE: To investigate the expressions of metastasis-associated in colon
      cancer-1 (MACC1), hepatocyte growth factor (HGF), and C-met proteins in
      epithelial ovarian cancer and their significance. METHODS: The expressions of
      MACC1, HGF and C-met in 20 specimens of normal ovarian tissues, 19 specimens of
      benign epithelial ovarian tumor and 52 specimens of epithelial ovarian cancer
      were measured  by immunohistochemistry and Western blotting. The correlations of
      the expressions of MACC1, HGF and C-met protein to the clinicopathologic
      characteristics of epithelial ovarian cancer were analyzed, and the correlations
      between the expressions of the 3 proteins were also evaluated. RESULTS: The
      positivity rates of MACC1, HGF and C-met proteins were 73.1%, 63.5% and 78.8% in
      epithelial ovarian cancer with relative expressions of 0.72?0.05, 0.64?0.04 and
      0.79?0.04, respectively, showing significant differences from those in normal
      ovarian tissues and benign ovarian tumors (P<0.05). In epithelial ovarian cancer,
      the up-regulation of MACC1, HGF and C-met expressions were associated with
      advanced FIGO stage, poor differentiation and lymph node metastasis (P<0.05).
      MACC1 expression was positively correlated to HGF (r=0.350, P=0.011) and C-met
      expressions (r=0.429, P=0.002), and the latter two was also positively correlated
      (r=0.487, P=0.000). CONCLUSIONS: MACC1 may serve as a potential biomarker for
      advanced ovarian cancer. Deregulation of MACC1, HGF and C-met proteins may
      synergistically participate in the malignant progression of epithelial ovarian
      cancer.

PMID- 21945765
TI  - [Cochlear implantation and rehabilitation in prelingually deafened adolescents
      and young adults].
AB  - OBJECTIVE: To investigate the outcomes of prelingually deafened adolescents and
      young adults receiving cochlear implantation (CI). METHODS: Thirty-three patients
      with prelingual deafness aged 7-33 years at the time of CI were followed up for 4
      years. The Speech Discrimination Score (SDS) was tested using disyllabic words
      and short sentences with close-set and open-set, respectively. RESULTS: After
      appropriate mapping, sound field audiometry with warble tone showed that the
      warble tone threshold average (WTA) of the patients reached 25-41 dBHL, with a
      mean threshold of 28.62?2.37 dBHL. At 1 year after the operation, the mean value
      of SDS was 70.03% in close-set word list with lip-reading and 61.18% without lip
      reading, and was improved to 82.12% and 72.67% at 4 years, respectively. In open
      set word list, the mean value of SDS was 77.94% with lip-reading and 67.85%
      without lip-reading. The safety and the benefits-cost evaluation of CI for
      prelingually deafened school age children and adolescents had been recognized by
      90.9% of the families involved. CONCLUSION: These patients can obtain appropriate
      speech discrimination scores with improved quality of life after CI.

PMID- 21945767
TI  - [Prostaglandin E2 promotes hepatocellular carcinoma cell proliferation through
      EP2 prostanoid receptor].
AB  - OBJECTIVE: To investigate the effect of prostaglandin E2 (PGE(2)) on the
      proliferation of cultured hepatocellular carcinoma cells and explore which
      subtypes of EP prostanoid receptor mediate the action. METHODS: RT-PCR was used
      to determine COX-2 and EP receptor mRNA expression levels in human hepatocellular
      carcinoma cell line Hep3B and human normal hepatocyte line QSG7701. Cell counting
      kit-8 (CCK-8) assay was employed to investigate the effect of PGE(2), selective
      EP2 receptor agonist butaprost and EP3/EP4 receptor agonist PGE1 alcohol on the
      proliferation of the cells. RESULTS: COX-2 mRNA was highly expressed in Hep3B
      cells but scarcely in QSG7701 cells. Hep3B cells expressed the mRNAs for all the
      EP receptor subtypes, but EP2 and EP4 receptors were much more strongly expressed
      than EP1 and EP3 receptors. PGE(2) significantly promoted Hep3B cell
      proliferation in a time- and dose-dependent manner, and 10 umol/L PGE(2)
      increased the cell proliferation by 22.57% (P<0.001) after a 48-h incubation;
      treatment with 0.1, 1.0, and 10 umol/L PGE(2) for 72 h resulted in significantly
      increased cell proliferation by 12.13% (P<0.01), 17.58% (P<0.01) and 33.07%
      (P<0.001), respectively. EP2 receptor agonist butaprost (20 umol/L) increased
      Hep3B cell proliferation by 21.96% (P<0.001), but the EP3/EP4 receptor agonist
      PGE(1) alcohol (2-20 umol/L) exhibited no significant mitogenic effect in Hep3B
      cells, and 200 umol/L PGE(1) alcohol decreased the cell viability. CONCLUSION:
      Selective activation of EP2 receptor promotes Hep3B cell proliferation,
      indicating the predominant role of EP2 receptor in mediating the mitogenic effect
      of PGE2.

PMID- 21945766
TI  - [Expression of translationally controlled tumor protein in human breast cancer
      and its clinical significance].
AB  - OBJECTIVE: To investigate the expression of translationally controlled tumor
      protein (TCTP) in human breast cancer tissues and its clinical significances.
      METHODS: The expression of TCTP in 94 human breast cancer and the corresponding
      adjacent normal mammary tissues were detected using immunohistochemistry.
      RESULTS: The expression rate of TCTP was 64.89% in human breast cancer tissues,
      significantly higher than that in normal benign mammary tissues (39.36%,
      P<0.001). TCTP overexpression was positively correlated to the tumor size,
      clinical stage, lymph node metastasis and histological grade of breast cancer
      (P<0.05). Patients with positive TCTP expression had a significantly shorter mean
      survival time than those with negative expression (P<0.001). CONCLUSION: TCTP may
      play an important role in the tumorigenesis and development of breast cancer, and
      can be an important prognostic factor for this malignancy.

PMID- 21945768
TI  - [Evaluation of chemomechanical and traditional mechanical caries removal in
      indirect pulp capping of symmetric primary molars].
AB  - OBJECTIVE: To evaluate the difference between chemomechanical and traditional
      mechanical caries removal in indirect pulp capping of the symmetric primary
      molars. METHODS: A total of 192 children with deep caries in the two symmetric
      primary molars were studied. The two symmetric primary molars were divided into
      two groups for treatment with chemomechanical method with Carisolv(TM) system or
      traditional mechanical method. After caries removal, calcium hydroxide agent was
      placed as the protective base, and glass ionomer cement was used to restore the
      teeth. The patients were followed up every 1 month within one year after the
      operation. RESULTS: The percentage of healthy primary molar pulp was 95.3% with
      chemomechanical method and 87.0% with traditional method, showing a significant
      difference between the two methods. CONCLUSION: Chemomechanical caries removal is
      more effective in preserving the healthy pulp than the traditional method.

PMID- 21945770
TI  - [CpG array analysis of histone H3 lysine 4 trimethylation in patients with IgA
      nephropathy].
AB  - OBJECTIVE: To investigate the aberrance of histone H3 lysine 4 trimethylation
      (H3K4me3) in patients with IgA nephropathy (IgAN). METHODS: In 15 patients with
      IgAN and 15 healthy volunteers, H3K4me3 variations in peripheral blood
      mononuclear cells (PBMCs) were analyzed using chromatin immunoprecipitation and
      microarray analysis (ChIP-chip). ChIP real-time PCR was used to validate the
      microarray results. Quantitative real-time PCR (qRT-PCR) was carried out to
      examine the correlations between the mRNA expression profiles and H3K4me3 levels.
      RESULTS: We identified 83 genes that displayed significant H3K4me3 differences in
      IgAN patients compared with healthy subjects. Among them, 39 genes showed
      increased H3K4me3 and 44 genes had decreased H3K4me3 levels. The results of ChIP
      real-time PCR were well consistent with the microarray data. Quantitative RT-PCR
      revealed the correlations between the mRNA expressions and the methylation levels
      of H3K4me3. CONCLUSION: IgAN patients have significant alterations in H3K4me3,
      and the genes with aberrant H3K4me3 may provide insights into the pathogenesis of
      IgAN.

PMID- 21945769
TI  - [Value of (18)F-FDG dual head coincidence imaging in predicting the efficacy of
      radioiodine therapy for papillary thyroid carcinoma with cervical lymph node
      metastasis].
AB  - OBJECTIVE: To assess the value of (18)F-FDG dual head coincidence imaging in the
      prediction of the efficacy of radioiodine therapy in patients with cervical lymph
      node (LN) metastasis of papillary thyroid carcinoma (PTC). METHODS: Thirty-six
      patients undergoing thyroidectomy and radioiodine ablation of the residual normal
      thyroid tissue received (18)F-FDG dual head coincidence imaging and then
      therapeutic (131)I-whole body imaging ((131)I-WBI) in the same week. According to
      those imaging results, the patients were divided into group I with positive
      results of both imaging examinations and group II with positive results by (131)I
      WBI but negative results by(18)F-FDG dual head coincidence imaging. All the
      patients were followed up for 6 months. RESULTS: In group I (14 patients), a
      total of 49 lesions were diagnosed as cervical LN metastases, and the total
      sensitivity differed significantly between (18)F-FDG dual head coincidence
      imaging and (131)I- WBI (67.3% vs 89.8%, P=0.027). In both groups, the total
      sensitivity of (18)F-FDG dual head coincidence imaging and (131)I-WBI showed a
      significant difference (26.0% vs 94.5%, P<0.001). The target and non-target ratio
      (T/NT) was identified as one of the factors affecting the radioiodine efficacy
      (P<0.001). In group II (22 patients), 76 lesions were diagnosed as cervical LN
      metastases. The effective rates of groups I and II were 35.7% and 81.8%, 
      respectively, showing a significant difference between them (P=0.011).
      CONCLUSION: (131)I-WBI is more sensitive than (18)F-FDG dual head coincidence
      imaging in detecting cervical LN metastasis in patients with PTC. Patients with
      cervical LN metastases who have positive results in both (131)I-WBI and (18)F-FDG
      dual head coincidence imaging tend to have a poorer response to the therapy than
      the patients with negative results in (18)F-FDG dual head coincidence imaging.
      The T/NT of the cervical LN metastases in (18)F-FDG dual head coincidence imaging
      is associated with the efficacy of radioiodine therapy.

PMID- 21945771
TI  - [Development of a visualization system for minimally invasive surgical abortion].
AB  - This article introduces the principle, structure and components of a
      visualization system for carrying out minimally invasive surgical abortion.
      Without altering the current surgical approach or increasing the surgical
      difficulty, the surgical system integrated a mini-CMOS image sensor and LED light
      and a visual device to allow fixed-point removal of the fetus or embryo in the
      minimally invasive surgery.

PMID- 21945772
TI  - [Clinical application of low-molecular-weight heparin (Fraxiparine) in rescuing
      venous crisis of island skin flap].
AB  - OBJECTIVE: To evaluate the clinical efficacy of low molecular weight heparin
      (Fraxiparine) in rescuing venous crisis of island skin flap. METHODS: Of the 73
      patients with venous crisis of island skin flap, 47 received subcutaneous
      injection of low-molecular-weight heparin (group I) and 26 were treated with
      phlebotomy, local compression and topical application of unfractionated heparin
      solution gauze (group II). RESULTS: The flap survival ratio was (88.46?8.64)% in
      group I and (38.37?6.53)% in group II (P<0.001). At 0, 2, and 4 h after injection
      of low-molecular-weight heparin, the activated partial thromboplastin time (APTT)
      was obviously delayed (24.28?6.71, 41.35?7.64 and 32.34?6.35, respectively,
      P<0.01), FXa:C level was significantly decreased (152.4?30.7, 65.8?24.4 and
      83.4?18.4, respectively, P<0.01), while FIIa:C level underwent no obvious
      alterations (155.70?31.61, 143.20?24.75, and 143.4?23.35, respectively, P=NS).
      CONCLUSION: Fraxiparine has good antithrombotic efficacy in rescuing venous
      crisis of island skin flap without adverse effect on systemic coagulation.

PMID- 21945773
TI  - [Clinical application of 64-slice computed tomographic angiography-based virtual
      colonoscopy in the diagnosis of colonic tumors].
AB  - OBJECTIVE: To investigate the clinical value of 64-slice computed tomographic
      angiography (CTA)-based virtual colonoscopy in the diagnosis of colonic tumors.
      METHODS: Philips/Brilliance 64 CT volumetric scanning was performed in 8 patients
      with colonic cancer and 2 with colonic polypi identified by postoperative
      pathological examination. Mimics software was used for surface rendering of the
      intestine with the Marching Cubes algorithm for 3-dimensional (3D) virtual
      endoscope (VE) reconstruction and CTA-based 3D reconstruction of the large
      intestine and the surrounding structures. The location, volume and appearance of
      the lesions displayed by the virtual techniques were compared with the
      pathological results. RESULTS: The 3D reconstruction was successfully completed
      in all the 10 cases, and the imaging diagnoses showed a total match with the
      pathological diagnoses. No significant differences were found between virtual
      endoscopy and CT virtual endoscopy. Virtual colonoscopy combined with digital
      model reconstruction provided valuable information for accurate identification of
      the position of the lesions and the complex adjacent anatomical structures.
      CONCLUSION: Virtual colonoscopy based on 64-slice CTA, when combined with 3D
      reconstruction technique, allows accurate display of the colonic lesions and
      potential metastasis, which can be crucial for clinical staging and surgical
      planning of colonic cancer.

PMID- 21945774
TI  - [Correlation of cardiac troponin T gene mutations to hypertrophic cardiomyopathy
      in Chinese patients].
AB  - OBJECTIVE: To study cardiac troponin T (TNNT2) gene mutations in Chinese patients
      with hypertrophic cardiomyopathy (HCM) and analyze the correlation between the
      genotype and phenotype. METHODS: Ninety-five unrelated Chinese patients with HCM
      and 120 control individuals were screened for TNNT2 gene mutations. Seven exons
      (8, 9, 10, 11, 14, 15, and 16) in the functional regions of TNNT2 gene were
      amplified using PCR and the products were sequenced. The patients with positive
      results underwent further family screening. RESULTS AND CONCLUSION: This study
      did not find any HCM-caused mutations in TNNT2 gene, a result different from the
      reported rates of TNNT2 gene mutation ranging from 10% to 20% in other nations,
      suggesting that TNNT2 gene is not a susceptible gene for HCM in Chinese
      population.

PMID- 21945775
TI  - [Variation of serum thyroid transcription factor-1 protein and its value in the
      diagnosis of lung carcinoma].
AB  - OBJECTIVE: To investigate the variation of serum thyroid transcription factor-1
      (TTF-1) in different patients and explore its significance in the diagnosis of
      lung carcinoma. METHODS: Dot-enzyme linked immunosorbent assay (dot-ELISA) and
      Leica Q500 MC image analysis system were used to quantitatively detect TTF-1
      protein in the serum samples from normal healthy adults and from patients with
      benign lung disease, lung cancer, thyroid carcinoma and non-thyroid carcinoma.
      RESULTS: The sensitivity, specificity, standardized positive predicative value,
      standardized negative predicative value, standardized accuracy and standardized
      wrong diagnostic rate of the method were 90.91%, 82.22%, 83.64%, 90.04%, 86.57%
      and 13.43%, respectively. The cutoff value of serum TTF-1 in healthy normal
      adults was 36.39, with a ROC value of 0.95. Serum TTF-1 PU was significantly
      higher in patients with lung adenocarcinoma, squamous cell lung carcinoma and
      thyroid carcinoma than in healthy adults and patients with benign lung diseases
      and non-thyroid carcinoma (P=0.000). Serum TTF-1 PU was similar in lung
      adenocarcinoma, squamous cell lung carcinoma, small cell lung carcinoma, large
      cell lung carcinoma and thyroid carcinoma (P=0.744, 0.677, and 0.333,
      respectively). Serum TTF-1 PU was greater than the PU in the corresponding
      homogenate of lung adenocarcinoma, squamous cell lung carcinoma, small cell lung
      carcinoma, large cell lung carcinoma and thyroid carcinoma (P=0.000). Serum and
      homogenate TTF-1 PU was correlated to TNM stage of lung cancer patients (P=0.000)
      but not to gender, tumor types, differentiation or lymph node metastasis.
      CONCLUSIONS: Lung adenocarcinoma, squamous cell lung carcinoma and thyroid
      carcinoma are suspected when serum TTF-1 PU is higher than 36.39. Serum TTF-1 is
      not helpful in differentiating the types of lung carcinomas and thyroid
      carcinoma. After exclusion of thyroid carcinoma, detection of serum TTF-1 can be
      helpful in the diagnosis of lung cancer. In different lung carcinomas and thyroid
      carcinomas, the serum TTF-1 is higher than the corresponding homogenate TTF-1
      level. Serum TTF-1 increases with the progression of TNM stage of lung carcinoma.

PMID- 21945776
TI  - [Six degree-of-freedom acquisition and analysis of jaw opening and closing with
      motion capture system].
AB  - OBJECTIVE: To explore the six degrees of freedom of jaw opening and closing
      movement with motion capture and analysis system to establish a quantitative
      method for studying mandibular movement and a digital basis for virtual reality
      study of mandibular movement. METHODS: In a male adult with normal dentition
      without temporomandibular joint disorders, 3 fluorescent markers were pasted in
      the upper dentition and 4 in the lower dentition. Six cameras of the motion
      capture system were arranged in a semi-circular fashion. The subject sat in front
      of the camera at an 80-cm distance with the Frankfort plane kept parallel to the
      horizontal plane. The degree-of-freedom (3 linear displacement and 3 angular
      displacement) of jaw opening and closing movement was obtained by collecting the
      marker motion. RESULTS: Six degrees of freedom of jaw opening and closing were
      obtained using the motion capture system. The maximum linear displacements of X,
      Y and Z axes were 5.888 089 cm, 0.782 269 cm, and 0.138 931 cm, and the minimum
      linear displacements were -3.649 83 cm, -35.961 2 cm, -5.818 63 cm, respectively.
      The maximum angular displacements of X, Y and Z axes were 0.760 088 degrees ,
      2.803 753 degrees , and 0.786 493 degrees , with the minimum angular
      displacements of -2.526 18 degrees , -0.625 94 degrees , and -25.429 8 degrees ,
      respectively. Variations of linear displacements during jaw opening and closing
      occurred mainly in the Y axis, and those of angular displacement occurred mainly
      in the Z axis. CONCLUSION: The six degree-of-freedom of mandibular movement can
      be accurately obtained with the motion capture system to allow quantitative
      examination of the mandibular movement.

PMID- 21945777
TI  - [Lentivirus-mediated RNA interference suppresses APRIL expression and enhances
      chemosensitivity in colorectal cancer cells].
AB  - OBJECTIVE: To investigate the effects of lentivirus-mediated RNA interference
      (RNAi) targeting a proliferation-inducing ligand (APRIL) on the chemosensitivity
      to 5-FU of colorectal cancer cell line LoVo. METHODS: The lentiviral vector siRNA
      APRIL was constructed and verified by PCR and DNA sequencing. LoVo cells were
      transfected with siRNA-APRIL plasmid, non-targeting siRNA plasmid, or empty
      plasmid. Forty-eight hours after the transfection, the cells were examined for
      APRIL expression using Western blot. Seventy-two hours after treatment with 10
      ug/ml 5-FU, flow cytometry was used to detect the cell apoptosis and cell cycle
      changes. The cell growth inhibition rate following 5-FU exposure was detected by
      MTT assay. RESULTS: PCR analysis and DNA sequencing demonstrated that the RNAi
      sequence targeting APRIL gene was successfully inserted into the lentiviral
      vector. siRNA-APRIL transfection resulted in obviously reduced expression of
      APRIL in LoVo cells. After 5-FU exposure, the apoptosis rate of siRNA-APRIL
      transfected cells were increased to (21.12?3.35)%, significantly higher than that
      in cells transfected with the non-targeting plasmid or the empty plasmid
      [(13.06?1.92)% and (12.28?1.79)%, respectively, P<0.01]; the cell number in G0/G1
      phase increased while that in G2/M phase decreased in siRNA-APRIL-transfected
      cells. The growth inhibition rate in siRNA-APRIL group was (59.67?5.03)%,
      significantly higher than that in the other two groups [(42.33?4.16)% and
      (39.67?4.73)%, respectively, P<0.01]. CONCLUSION: Lentivirus-mediated RNAi
      targeting APRIL can effectively suppress the expression of APRIL in LoVo cells
      and enhance the chemosensitivity of the cells to 5-FU.

PMID- 21945778
TI  - [Rapid detection of chromosome number aberration in spontaneously aborted fetuses
      using fluorescence in situ hybridization].
AB  - OBJECTIVE: To assess the value of fluorescence in situ hybridization (FISH) in
      the diagnosis of common chromosome number aberration in spontaneously aborted
      fetuses. METHOD: A total of 100 spontaneously aborted fetuses were analyzed by G
      banding and by FISH to test chromosome number aberration mainly for chromosomes
      13, 18, 21, X and Y, and the results of FISH test was assessed according to those
      by G-banding test. RESULTS: FISH results were well consistent with those by G
      banding test. FISH test identified trisomy in 32 samples and polyploidy in 7
      samples. Two samples with cell culture failure were found to have trisomy 16 by
      FISH. Discrepancies in the results between the two tests occurred in 3 samples,
      but the results of FISH were verified by other methods. Kappa test between FISH
      technology and G-banding showed a good consistency between FISH and karyotyping
      (P<0.05). CONCLUSION: FISH is an effective and rapid method for detecting
      chromosome number aberration in spontaneously aborted fetuses, and the
      combination of FISH and karyotyping provides more reliable diagnostic evidence.

PMID- 21945779
TI  - [Safety and efficacy of Sorafenib in treatment of tumor recurrence in liver
      transplantation recipients].
AB  - OBJECTIVE: To investigate the therapeutic effect and safety of Sorafenib in the
      treatment of tumor recurrence after orthotopic liver transplantation (OLT).
      METHODS: Between January, 2009 and June, 2011, 10 patients with tumor recurrence
      after OLT were treated with Sorafenib (group A) and another 8 recipients received
      no Sorafenib treatment (group B); 25 patients with hepatocellular carcinoma (HCC)
      also received Sorafenib treatment (group C). The tumor-bearing survival time,
      adverse effect and toxicity associated with sorafenib were compared between the 3
      groups. RESULTS: In group A, the median tumor-bearing survival time was 10 months
      (5-22 months), as compared to 4 months (1-8 months) in group B and 4 months (2-21
      months) in group C, showing a significant difference in the survival time among
      the 3 groups (Kaplan-Meier, log-rank test, P=0.045). No recipient experienced
      acute graft rejection, but one recipient in group A died due to gastrointestinal
      bleeding. No significant difference was found in adverse effects associated with
      Sorafenib between groups A and C (P<0.05). CONCLUSION: Sorafenib can prolong the
      survival time of patients with tumor recurrence after OLT without increasing the
      risk of acute graft rejection.

PMID- 21945780
TI  - [Influence of serum prolactin on interleukin-6 secretion by peripheral blood
      mononuclear cells in patients with systemic lupus erythematosus].
AB  - OBJECTIVE: To detect serum prolactin (PRL) level in patients with systemic lupus
      erythematosus (SLE) and its correlations to SLE activity and interleukin-6 (IL-6)
      by peripheral blood mononuclear cells (PBMCs). METHODS: An
      electrochemiluminescence assay was employed to examine the serum content of PRL
      in 40 SLE patients and 20 healthy subjects, and the levels of IL-6 secretion by
      the PBMCs were detected using enzyme-linked immunosorbent assay. RESULTS: SLE
      patients showed a significantly higher serum level of PRL than healthy subjects,
      which was especially obvious in the active stage of the disease (P=0.000. Serum
      PRL in SLE patients was found to positively correlate to SLE Disease Activity
      Index (SLEDAI) (r=0.568, P=0.000). SLE patients with hyperprolactinemia showed a
      significantly higher level of IL-6 secretion by the PBMCs than those with normal
      serum PRL level (P=0.000). IL-6 secretion by the PBMCs isolated from SLE patients
      with normal PRL level and from healthy controls, especially the latter, increased
      significantly after stimulation of the cells with recombinant human PRL in vitro
      (P=0.000). CONCLUSION: Serum PRL may play a role in the pathogenesis of SLE. An
      elevated PRL level is closely related to SLE activity and can be used to assess
      SLE activity. Increased serum PRL level can up-regulate the secretion of IL-6 by
      the PBMCs.

PMID- 21945781
TI  - [ANGPTL4 gene silencing by short-hairpin RNA inhibits the migration of human
      colorectal cancer cell line HT29].
AB  - OBJECTIVE: To investigate the effect of ANGPTL4 gene silencing on the migration
      of human colon cancer cells in vitro. METHODS: The expression of ANGPTL4 in human
      colorectal cancer cell lines was detected by semi-quantitative RT-PCR. Following
      stable transfection with a short-hairpin RNA (shRNA) targeting ANGPTL4 gene in
      HT29 cells, ANGPTL4 mRNA and protein expressions were detected by semi
      quantitative RT-PCR and direct ELISA, respectively, and the changes in cell
      migration ability and cell morphology were observed with transwell and
      immunofluorescence assays. RESULTS: ANGPTL4 was expressed in most of the
      colorectal cancer cell lines. Compared with the control groups, HT29 cells with
      shRNA-mediated ANGPTL4 gene silencing showed significantly decreased expression
      of ANGPTL4 mRNA and protein (P<0.05) and lowered cell migration ability possibly
      due to decreased pseudopodia formation. CONCLUSION: ANGPTL4 was expressed in most
      colorectal cancer cell lines. Decreased ANGPTL4 gene expression can inhibit the
      cell migration and pseudopodia formation in HT29 cells.

PMID- 21945782
TI  - [Laparoendoscopic single-site surgery for gynecologic malignancy: the first
      report in China].
AB  - OBJECTIVE: To report the first case of laparoendoscopic single-site surgery
      (LESS) for gynecologic malignancy in China and discuss the application of LESS in
      minimally invasive gynecologic surgery. METHODS: A 57-year-old postmenopausal
      woman presented with vaginal bleeding for 5 years and diagnostic curettage
      revealed endometrial cancer. Staged LESS for endometrial cancer was performed
      using a single multiple-channel port (Tri-port) inserted through a solitary 2.5
      cm upper umbilicus incision. RESULTS: The operation was completed successfully.
      The total operative time was 4.5 h, the duration of the LESS procedure was 4.0 h,
      and the establishment of the operative access took 1.0 h. No other port incision
      or transfer to open procedure was needed. The intraoperative blood loss was 100
      ml. Bowel peristalsis and micturition recovered 2 days after the operation, and
      the peritoneal drainage tube was removed 4 days after the operation without
      vaginal bleeding. No obvious scar was left on the surface of umbilicus.
      CONCLUSION: LESS can be a promising minimally invasive approach to effective
      management of benign and malignant gynecological diseases.

PMID- 21945783
TI  - [Value of contrast-enhanced ultrasound imaging in monitoring malignant tumor
      during argon-helium cryosurgery].
AB  - OBJECTIVE: To assess the value of contrast-enhanced ultrasound imaging in
      monitoring the therapeutic effect of argon-helium cryosurgical treatment of
      malignant tumors. METHODS: Before and after argon-helium cryosurgical treatment,
      42 patients underwent contrast-enhanced ultrasound imaging, conventional
      ultrasound imaging and enhanced CT or magnetic resonance imaging (MRI) for
      examining the number of tumor foci and the size of necrotic areas. RESULTS: A
      total of 80 tumor lesions were detected by contrast-enhanced ultrasound imaging.
      Compared with conventional ultrasound imaging, contrast-enhanced ultrasound
      imaging detected a significantly greater number of tumors and the intratumoral
      necrotic areas (96 vs 19) as well as a significantly increased mean size of
      necrotic areas (5.7?3.6 cm vs 2.8?1.7 cm), showing no significant differences
      from the results by enhanced CT and MRI (94 and 5.5?3.3 cm, P=0.872 and 0.978,
      respectively). The short-term therapeutic effect of argon-helium cryosurgery
      evaluated by contrast-enhanced ultrasound imaging were also similar to that
      assessed by enhanced CT or MRI (P=0.906). CONCLUSION: Contrast-enhanced
      ultrasound imaging has important values in monitoring malignant tumors during
      argon-helium cryosurgical treatment and in evaluating the short-term therapeutic
      effect of the treatment.

PMID- 21945784
TI  - [Establishment and evaluation of a modified plasma protamine paracoagulation
      test].
AB  - OBJECTIVE: To establish a modified plasma protamine paracoagulation test.
      METHODS: Plasma protamine paracoagulation, modified plasma protamine
      paracoagulation and D-dimer (D-D) tests were performed for the plasma samples
      collected from 98 cases of disseminated intravascular coagulation (DIC) and 156
      normal subjects. The sensitivity and specificity of the 3 tests were analyzed.
      The plasma samples from 8 cases of suspected myocardial infarction were detected
      using modified plasma protamine paracoagulation for diagnostic purpose. RESULTS:
      The sensitivity of plasma protamine paracoagulation, modified plasma protamine
      paracoagulation and D-D tests was 16.33%, 88.76% and 77.56%, and the specificity
      was 100%, 88.46% and 97.44%, respectively. Positive results occurred earlier in
      modified plasma protamine paracoagulation test than in plasma protamine
      paracoagulation and D-D tests in 5 cases of myocardial infarction. CONCLUSION:
      The modified plasma protamine paracoagulation test has a higher sensitivity than
      plasma protamine paracoagulation test and a higher specificity than D-D test, and
      can be helpful in early diagnosis of thrombosis and fibrinolysis.

PMID- 21945785
TI  - [Perioperative management of HIV infection/AIDS in gynecological and obstetric
      patients].
AB  - OBJECTIVE: To investigate the optimal perioperative management of HIV
      infection/AIDS in surgical patients in the department of gynecology and
      obstetrics. METHODS: Fifty-seven surgical patients with HIV infection or AIDS
      were studies. Before the operations, the patients were treated with highly active
      anti-retroviral therapy (HAART), and the surgical approach was determined
      according to the level of CD4(+) T lymphocytes. The operations were performed
      strictly following the standard procedures with careful operation to reduce
      surgical injuries. Routine antibiotics were administered to prevent postoperative
      infections. The white blood cell count, hemoglobin and CD4(+) T lymphocytes
      recorded pre- and postoperatively were analyzed for evaluation of the
      perioperative management and therapeutic effects. RESULTS: With these
      perioperative managements, the white blood cells and CD4(+) T lymphocytes showed
      no significant changes after the operation (P>0.05) and no wound infections or
      opportunistic infections were found in these cases. CONCLUSIONS: Appropriate
      perioperative management can ensure surgical success in patients with HIV
      infection or AIDS in the department of gynecology and obstetrics.

PMID- 21945786
TI  - [Clinical and pathological analysis of 25 cases of microscopic polyangiitis].
AB  - OBJECTIVE: To analyze the clinical and pathological features of microscopic
      polyangiitis (MPA) to improve the diagnosis and treatment of the disease.
      METHODS: Twenty-five cases of MPA were retrospectively analyzed. RESULTS: The
      onset symptoms of MPA, often nonspecific, included fever, muscle and joint pain,
      fatigue, loss of weight, etc, with varying degrees of proteinuria, hematuria and
      renal insufficiency. The pathological types revealed by renal biopsy were mainly
      focal segmental necrotizing glomerulonephritis or pauci-immune crescentic
      glomerulonephritis. Timely immunosuppressive therapy could improve the outcome.
      CONCLUSION: The early symptoms of MPA are often nonspecific to easily result in
      misdiagnosis. Examination of ANCA titers and timely renal biopsy are helpful to
      establish an early diagnosis. Immune suppression therapy and plasma exchange when
      necessary should be initiated after the establishment of the diagnosis. The
      disease activity and drug toxicity should be carefully monitored to improve the
      prognosis.

PMID- 21945787
TI  - Cytotoxicity and mechanical behavior of chitin-bentonite clay based polyurethane
      bio-nanocomposites.
AB  - Chitin based polyurethane bio-nanocomposites (PUBNC) were prepared using chitin,
      Delite HPS bentonite nanoclay enriched in montmorillonite (MMT), 4,4'
      diphenylmethane diisocyanate (MDI) and polycaprolactone polyol CAPA 231 (3000
      g/mol(-1)). The prepolymers having different concentration of Delite HPS
      bentonite nanoclay were extended with 2 moles of chitin. The structures of the
      resulted polymers were determined by FT-IR technique. The effect of nanoclay
      contents on mechanical properties and in vitro biocompatibility was investigated.
      The mechanical properties of the synthesized materials were improved with
      increase in the Delite HPS bentonite nanoclay contents. Optimum mechanical
      properties were obtained from the PU bio-nanocomposite samples having 4% Delite
      HPS bentonite nanoclay. The results revealed that the final PU bio-nanocomposite
      having 2% Delite HPS bentonite nanoclay contents is ideal contenders for surgical
      threads with on going investigations into their in vitro biocompatibility, non
      toxicity, and mechanical properties.

PMID- 21945788
TI  - Dating the arthropod tree based on large-scale transcriptome data.
AB  - Molecular sequences do not only allow the reconstruction of phylogenetic
      relationships among species, but also provide information on the approximate
      divergence times. Whereas the fossil record dates the origin of most
      multicellular animal phyla during the Cambrian explosion less than 540 million
      years ago(mya), molecular clock calculations usually suggest much older dates.
      Here we used a large multiple sequence alignment derived from Expressed Sequence
      Tags and genomes comprising 129genes (37,476 amino acid positions) and 117 taxa,
      including 101 arthropods. We obtained consistent divergence time estimates
      applying relaxed Bayesian clock models with different priors and multiple
      calibration points. While the influence of substitution rates, missing data, and
      model priors were negligible, the clock model had significant effect. A log
      normal autocorrelated model was selected on basis of cross-validation. We
      calculated that arthropods emerged ~600 mya. Onychophorans (velvet worms) and
      euarthropods split ~590 mya, Pancrustacea and Myriochelata ~560 mya, Myriapoda
      and Chelicerata ~555 mya, and 'Crustacea' and Hexapoda ~510 mya. Endopterygote
      insects appeared ~390 mya. These dates are considerably younger than most
      previous molecular clock estimates and in better agreement with the fossil
      record. Nevertheless, a Precambrian origin of arthropods and other metazoan phyla
      is still supported. Our results also demonstrate the applicability of large
      datasets of random nuclear sequences for approximating the timing of
      multicellular animal evolution.

PMID- 21945789
TI  - Cortical responses to changes in acoustic regularity are differentially modulated
      by attentional load.
AB  - This study investigates how acoustic change-events are represented in a
      listener's brain when attention is strongly focused elsewhere. Using magneto
      encephalography (MEG) we examine whether cortical responses to different kinds of
      changes in stimulus statistics are similarly influenced by attentional load, and
      whether the processing of such acoustic changes in auditory cortex depends on
      modality-specific or general processing resources. We investigated these issues
      by examining cortical responses to two basic forms of acoustic transitions: (1)
      Violations of a simple acoustic pattern and (2) the emergence of a regular
      pattern from a random one. To simulate a complex sensory environment, these
      patterns were presented concurrently with streams of auditory and visual decoys.
      Listeners were required to perform tasks of high- and low-attentional-load in
      these domains. Results demonstrate that while auditory attentional-load does not
      influence the cortical representation of simple violations of regularity, it
      significantly reduces the magnitude of responses to the emergence of a regular
      acoustic pattern, suggesting a fundamentally skewed representation of the
      unattended auditory scene. In contrast, visual attentional-load had no effect on
      either transition response, consistent with the hypothesis that processing
      resources necessary for change detection are modality-specific.

PMID- 21945791
TI  - Expectancy and surprise predict neural and behavioral measures of attention to
      threatening stimuli.
AB  - Attention is preferentially deployed toward those stimuli which are threatening
      and those which are surprising. The current paper examines the intersection of
      these phenomena; how do expectations about the threatening nature of stimuli
      influence the deployment of attention? The predictions tested were that
      individuals would direct attention toward stimuli which were expected to be
      threatening (regardless of whether they were or not) and toward stimuli which
      were surprising. As anxiety has been associated with deficient control of
      attention to threat, it was additionally predicted that high levels of trait
      anxiety would be associated with deficits in the use of threat-expectation to
      guide attention. During fMRI scanning, 29 healthy volunteers completed a simple
      task in which threat-expectation was manipulated by altering the frequency with
      which fearful or neutral faces were presented. Individual estimates of threat
      expectation and surprise were created using a Bayesian computational model. The
      degree to which the model derived estimates of threat-expectation and surprise
      were able to explain both a behavioral measure of attention to the faces and
      activity in the visual cortex and anterior attentional control areas was then
      tested. As predicted, increased threat-expectation and surprise were associated
      with increases in both the behavioral and neuroimaging measures of attention to
      the faces. Additionally, regions of the orbitofrontal cortex and left amygdala
      were found to covary with threat-expectation whereas anterior cingulate and
      lateral prefrontal cortices covaried with surprise. Individuals with higher
      levels of trait anxiety were less able to modify neuroimaging measures of
      attention in response to threat-expectation. These results suggest that
      continuously calculated estimates of the probability of threat may plausibly be
      used to influence the deployment of visual attention and that use of this
      information is perturbed in anxious individuals.

PMID- 21945792
TI  - Vascular component analysis of hyperoxic and hypercapnic BOLD contrast.
AB  - Hyperoxia or hypercapnia provides a useful experimental tool to systematically
      alter the blood oxygenation level dependent (BOLD) contrast. Typical applications
      include calibrated functional magnetic resonance imaging (fMRI), BOLD sensitivity
      mapping, vessel size imaging or cerebrovascular reactivity mapping. This article
      describes a novel biophysical model of hyperoxic and hypercapnic BOLD contrast,
      which accounts for the magnetic susceptibility effects of molecular oxygen that
      is dissolved in blood and tissue, in addition to the well-established effects
      caused by the paramagnetic properties of deoxyhaemoglobin. Furthermore, the
      concept of vascular component analysis (VCA) is introduced and is shown to
      provide a computationally efficient tool for investigating the vascular
      specificity of hyperoxic and hypercapnic BOLD contrast. A theoretical
      investigation of gradient and spin echo BOLD contrast based on computer
      simulations was performed to compare three different conditions (hypercapnia
      induced by breathing 6% CO2, hyperoxia induced by breathing 100% O2, and
      simultaneous hypercapnia and hyperoxia induced by breathing carbogen, i.e. 5% CO2
      in 95% CO2) with baseline (breathing air). Simulations were carried out for
      different levels of metabolic oxygen extraction fraction (OEF) ranging from 0 to
      0.5. The key findings can be summarised as follows: (i) for hyperoxia the
      susceptibility of dissolved O2 may lead to a significant arterial BOLD contrast;
      (ii) under normoxic conditions the susceptibility of dissolved O2 is negligible;
      (iii) an almost complete loss of BOLD sensitivity may occur at lower OEF values
      in all parts of the vascular tree, whereas hyperoxic BOLD sensitivity is largely
      maintained; (iv) under hyperoxic conditions, a transition from positive to
      negative BOLD contrast occurs with decreasing OEF values. These findings have
      important implications for experimental applications of hyperoxic and hypercapnic
      BOLD contrast and may enable new clinical applications in ischemic stroke and
      other forms of acquired brain injury.

PMID- 21945790
TI  - Complex relationships between cerebral blood flow and brain atrophy in early
      Huntington's disease.
AB  - Alterations in cerebral blood flow (CBF) may play an important role in the
      pathophysiology of neurodegenerative disorders such as Huntington's disease (HD).
      While a few reports have suggested reductions in CBF in HD, little is known about
      their extent and whether, or how, they might be related to atrophy and to
      clinical symptoms. We used pulsed arterial-spin labeling MRI in conjunction with
      high-resolution anatomical MRI to non-invasively measure regional CBF in 17 early
      stage HD subjects and 41 age- and gender-matched healthy controls. We found
      profound yet heterogeneous CBF reductions in the cortex, extending to the
      sensorimotor, paracentral, inferior temporal and lateral occipital regions, with
      sparing of the neighboring postcentral gyrus, insula and medial occipital areas.
      As expected, CBF in subcortical regions was also profoundly reduced, and to a
      similar degree. Unexpectedly, however, the association between CBF reductions and
      regional atrophy was complex, the two being directly associated in certain areas
      but not with others. In contrast, CBF was associated with performance on the
      Stroop, suggesting a potentially important role for alterations in CBF in
      cognitive deficits in HD. The work described here may have broad-reaching
      implications for our understanding of HD pathogenesis, progression and emerging
      therapies.

PMID- 21945793
TI  - Short separation channel location impacts the performance of short channel
      regression in NIRS.
AB  - Near-Infrared Spectroscopy (NIRS) allows the recovery of cortical oxy- and
      deoxyhemoglobin changes associated with evoked brain activity. NIRS is a back
      reflection measurement making it very sensitive to the superficial layers of the
      head, i.e. the skin and the skull, where systemic interference occurs. As a
      result, the NIRS signal is strongly contaminated with systemic interference of
      superficial origin. A recent approach to overcome this problem has been the use
      of additional short source-detector separation optodes as regressors. Since these
      additional measurements are mainly sensitive to superficial layers in adult
      humans, they can be used to remove the systemic interference present in longer
      separation measurements, improving the recovery of the cortical hemodynamic
      response function (HRF). One question that remains to answer is whether or not a
      short separation measurement is required in close proximity to each long
      separation NIRS channel. Here, we show that the systemic interference occurring
      in the superficial layers of the human head is inhomogeneous across the surface
      of the scalp. As a result, the improvement obtained by using a short separation
      optode decreases as the relative distance between the short and the long
      measurement is increased. NIRS data was acquired on 6 human subjects both at rest
      and during a motor task consisting of finger tapping. The effect of distance
      between the short and the long channel was first quantified by recovering a
      synthetic hemodynamic response added over the resting-state data. The effect was
      also observed in the functional data collected during the finger tapping task.
      Together, these results suggest that the short separation measurement must be
      located as close as 1.5 cm from the standard NIRS channel in order to provide an
      improvement which is of practical use. In this case, the improvement in Contrast
      to-Noise Ratio (CNR) compared to a standard General Linear Model (GLM) procedure
      without using any small separation optode reached 50% for HbO and 100% for HbR.
      Using small separations located farther than 2 cm away resulted in mild or
      negligible improvements only.

PMID- 21945794
TI  - Turning on the alarm: the neural mechanisms of the transition from innocuous to
      painful sensation.
AB  - The experience of pain occurs when the level of a stimulus is sufficient to
      elicit a marked affective response, putatively to warn the organism of potential
      danger and motivate appropriate behavioral responses. Understanding the
      biological mechanisms of the transition from innocuous to painful levels of
      sensation is essential to understanding pain perception as well as clinical
      conditions characterized by abnormal relationships between stimulation and pain
      response. Thus, the primary objective of this study was to characterize the
      neural response associated with this transition and the correspondence between
      that response and subjective reports of pain. Towards this goal, this study
      examined BOLD response profiles across a range of temperatures spanning the pain
      threshold. 14 healthy adults underwent functional magnetic resonance imaging
      (fMRI) while a range of thermal stimuli (44-49 degrees C) were applied. BOLD
      responses showed a sigmoidal profile along the range of temperatures in a network
      of brain regions including insula and mid-cingulate, as well as a number of
      regions associated with motor responses including ventral lateral nuclei of the
      thalamus, globus pallidus and premotor cortex. A sigmoid function fit to the BOLD
      responses in these regions explained up to 85% of the variance in individual pain
      ratings, and yielded an estimate of the temperature of steepest transition from
      non-painful to painful heat that was nearly identical to that generated by
      subjective ratings. These results demonstrate a precise characterization of the
      relationship between objective levels of stimulation, resulting neural
      activation, and subjective experience of pain and provide direct evidence for a
      neural mechanism supporting the nonlinear transition from innocuous to painful
      levels along the sensory continuum.

PMID- 21945795
TI  - Correction of geometric distortion in fMRI data.
AB  - The early functional MRI research programme at the National Institutes of Health,
      described by Robert Turner in an accompanying article in this volume, was the
      first to combine echo planar imaging (EPI) and high field in the pursuit of fMRI.
      As such, it soon became apparent that one of the obstacles to interpreting fMRI
      data using EPI was the presence of geometric distortions caused by static field
      inhomogeneities. This meant that EPI data did not properly align spatially with
      conventionally acquired MRI scans that showed structural information. This
      article describes some of the approaches that have been adopted to ensure that
      spatial warping caused by field inhomogeneities can be corrected so that
      functional and structural information can be co-aligned.

PMID- 21945796
TI  - The effect of different physiotherapy interventions in post-BTX-A treatment of
      children with cerebral palsy.
AB  - AIM: To distinguish the effects of different physiotherapeutic programs in a post
      BTX-A regime for children with Cerebral Palsy (CP). DESIGN: Retrospective,
      controlled intervention study. PARTICIPANTS AND INTERVENTIONS: A group of 38
      children (X- = 7y7m, GMFCS I-III, 27 bilateral, 11 unilateral CP) receiving an
      individually defined Neurodevelopment Treatment (NDT) program, was matched and
      compared to a group of children with the same age, GMFCS and diagnosis, receiving
      more conventional physiotherapy treatment. All patients received selective tone
      reduction by means of multilevel BTX-A injections and adequate follow-up
      treatment, including physiotherapy. OUTCOME MEASURES: Three-dimensional gait
      analyses and clinical examination was performed pre and two months post
      injection. Treatment success was defined using the Goal Attainment Scale (GAS).
      RESULTS: Both groups' mean converted GAS scores were above 50. The average
      converted GAS score was higher in the group of children receiving NDT than in the
      group receiving conventional physiotherapy (p < 0.05). In the NDT group, overall
      treatment success was achieved in 76% of the goals, compared to 67% of the goals
      defined for the conventional physiotherapy group. Especially for the goals based
      on gait analyses (p < 0.05) and in the group of children with bilateral CP (p <
      0.05), treatment success was higher in the NDT group. CONCLUSION: In a post-BTX-A
      regime, the short-term effects of an NDT approach are more pronouncedthan these
      from a conventional physiotherapy approach.

PMID- 21945797
TI  - Ethosuximide modifies network excitability in the rat entorhinal cortex via an
      increase in GABA release.
AB  - Ethosuximide is the drug of choice for treating generalized absence seizures, but
      its mechanism of action is still a matter of debate. It has long been thought to
      act by disrupting a thalamic focus via blockade of T-type channels and, thus,
      generation of spike-wave activity in thalamocortical pathways. However, there is
      now good evidence that generalized absence seizures may be initiated at a
      cortical focus and that ethosuximide may target this focus. In the present study
      we have looked at the effect ethosuximide on glutamate and GABA release at
      synapses in the rat entorhinal cortex in vitro, using two experimental
      approaches. Whole-cell patch-clamp studies revealed an increase in spontaneous
      GABA release by ethosuximide concurrent with no change in glutamate release. This
      was reflected in studies that estimated global background inhibition and
      excitation from intracellularly recorded membrane potential fluctuations, where
      there was a substantial rise in the ratio of network inhibition to excitation,
      and a concurrent decrease in excitability of neurones embedded in this network.
      These studies suggest that, in addition to well-characterised effects on ion
      channels, ethosuximide may directly elevate synaptic inhibition in the cortex and
      that this could contribute to its anti-absence effects. This article is part of a
      Special Issue entitled 'Post-Traumatic Stress Disorder'.

PMID- 21945798
TI  - Investigating anxiety and depressive-like phenotypes in genetic mouse models of
      serotonin depletion.
AB  - Emotional disorders such as depression, panic attacks, generalized anxiety,
      phobias and post-traumatic stress have been associated to decreased serotonin (5
      HT) function, based on the positive effects of treatments that enhance 5-HT
      neurotransmission. However, it has been difficult to establish a primary role for
      5-HT deficiency in these diseases, making preclinical models particularly useful.
      Over the last ten years a variety of genetic mouse models of 5-HT depletion have
      been produced, complementing previous pharmacologically-based models. Initial
      models hindered the differentiation of the raphe 5-HT neurons, while more
      recently produced models suppressed 5-HT production or incapacitated 5-HT
      vesicular packaging and release in normally developed raphe neurons. Here, we
      provide an overview of 11 genetic mouse models with lowered 5-HT transmission and
      summarize the available behavioural investigations concerning their anxiety and
      depression phenotypes. Although these studies are still ongoing, some common
      anxiety-related traits and behavioural phenotypes have emerged. Most studies have
      reported decreased innate anxiety to novelty but heightened fear responses to
      conditioned aversive cues. This complex phenotype is in general agreement with
      the proposed dual function of 5-HT in modulating different defensive behaviours.
      Surprisingly, the depressive-like behaviours have been less studied and, so far,
      did not yield a consistent phenotype in standard tests. Future studies should be
      conducted using more ethological relevant models to conclude on the causal role
      of 5-HT depletion in depression. This review also describes the differences in
      level and regional distribution of 5-HT depletion among the available mouse
      models, which could contribute to the diverse phenotypes observed. This article
      is part of a Special Issue entitled 'Anxiety and Depression'.

PMID- 21945799
TI  - The antidepressant-like effects of the 3beta-hydroxysteroid dehydrogenase
      inhibitor trilostane in mice is related to changes in neuroactive steroid and
      monoamine levels.
AB  - In the present study, we analyzed the effects of a systemic treatment with the
      competitive 3beta-hydroxysteroid dehydrogenase (3beta-HSD) inhibitor trilostane
      on: (i) neurosteroid and monoamine levels in the brain, and (ii) the
      antidepressant activity of steroids and antidepressants in the forced swimming
      test (FST). 3beta-HSD converts pregnenolone (PREG) into progesterone (PROG) or
      dehydroepiandrosterone (DHEA) into androstenedione. These neuroactive steroids
      are known to regulate neurotransmitters effects in the brain, particularly
      glutamate, gamma-aminobutyric acid (GABA) and serotonin (5-HT), with consequences
      on mood and depression. We previously reported that trilostane showed
      antidepressant-like properties in the FST and concomitantly regulated plasma
      adrenocorticotropin (ACTH) and corticosterone levels, markers of the stress
      induced hypothalamus-pituitary-adrenal (HPA) axis activation. We here observed
      that adrenalectomy/castration blocked the trilostane effect, outlining the
      importance of peripheral steroid levels. Trilostane (25 mg/kg) decreased
      hippocampus PROG contents and paradoxically increased circulating PROG levels. It
      also increased PREG levels in the hippocampus and frontal cortex. In the FST, a
      co-treatment with trilostane facilitated DHEAS (5-20 mg/kg) antidepressant
      activity, but showed only an additive, not facilitative, effect with PREGS (10-40
      mg/kg), PROG (10-40 mg/kg) or allopregnanolone (ALLO, 1-8 mg/kg). Trilostane (25
      mg/kg) treatment significantly increased 5-HT and (-)-norepinephrine (NE)
      turnovers in the hippocampus, an effect likely related to its antidepressant
      action. In co-administration studies, trilostane further decreased immobility
      following fluoxetine (30-60 mg/kg), sertraline (20-40 mg/kg) and imipramine (20
      40 mg/kg), but not desipramine (20-40 mg/kg), treatments. A significant additive
      effect was observed for the selective 5-HT reuptake inhibitors (SSRI) at their
      highest dose. This study confirmed that a systemic administration of trilostane
      directly affected peripheral and brain levels in neuroactive steroids and
      monoamine turnover, resulting in antidepressant activity. The drug could be
      proposed as a co-treatment with SSRI. This article is part of a Special Issue
      entitled 'Anxiety and Depression'.

PMID- 21945800
TI  - Molecular cloning, sequencing, and expression of the outer membrane protein P2
      gene of Haemophilus parasuis.
AB  - Haemophilus parasuis is the etiological agent of Glasser's disease characterized
      by fibrinous polyserositis, polyarthritis, and meningitis in young pigs. But it
      is difficult to develop universal serological diagnostic tools and effective
      vaccines against this disease because of the serovar diversity of the isolates.
      In this study, enterobacterial repetitive intergenic consensus-polymerase chain
      reaction, were performed to investigate the gene profile of 111 isolates of H.
      parasuis from China. And a specific common gene of H. parasuis was cloned and
      identified as the outer-membrane protein (OMP) P2 gene. Sequencing results of OMP
      P2 genes of 22 isolates showed that they had high homology and could be divided
      into 2 genetic types. Moreover, the OMPP2 protein was expressed in Escherichia
      coli expressing system. And the purified recombinant protein provided partial
      protection against H. parasuis infection in mice. It suggested the OMP P2 was an
      immunogenic protein and had great potential to serve as a vaccine and diagnostic
      antigen.

PMID- 21945801
TI  - Risk factors for local spread of foot-and-mouth disease, 2010 epidemic in Japan.
AB  - To provide a basis for effective foot-and-mouth disease (FMD) prevention
      measures, factors associated with local spread were investigated in this study
      using data of the 2010 FMD epidemic in Japan. Thirty-eight local clusters within
      a 500-m radius from source farms were selected. In the clusters with pig source
      farms, more neighboring farms were infected in a short time compared with the
      clusters with cattle source farms. The influence of distance and wind upon local
      spread did not show a significant difference between infected and noninfected
      neighboring farms. Large-size pig farms posed a greater risk of inducing local
      spread; the odds ratio with reference to small-size cattle farms was 16.73.
      Middle-size and large-size cattle farms had a greater risk of infection; odds
      ratios with reference to small-size cattle farms were 15.65 and 25.52,
      respectively. The present results are useful for understanding features of local
      spread and prioritizing farms for control measures.

PMID- 21945802
TI  - Isolation, expansion, and differentiation of goat adipose-derived stem cells.
AB  - A goat adipose-derived stem cell (ADSC) line was established and compared to a
      rat line. Goat ADSC cells had normal diploidy after subculture. Proliferation of
      goat ADSCs was faster than rat cells in the same conditions. Both rat and goat
      ADSCs stained positively for vimentin, CD49d, CD44 and CD13, but stained
      negatively for CD34 and CD106. Bone nodules were apparent, and alizarin staining
      was positive after osteogenic induction. Cells expressing osteocalcin were
      positive by alkaline phosphatase (ALP) staining. After osteogenic induction,
      ossification nodules of goat ADSCs were larger than in rats, with dense ALP
      staining. Adipogenic induction resulting in lipid droplets and peroxisome
      proliferator-activated receptor (PPARgamma2) expression were observed. Cartilage
      lacunae were formed and COL2A1 was expressed. More cartilage lacunae with better
      morphology were seen following differentiation of goat ADSC's using the hang-drop
      method. For goat ADSCs, results with both adherent-induced and hanging-drop
      induced cultures were better than for three-dimensional cultures.

PMID- 21945803
TI  - Substance P induces CCN1 expression via histone deacetylase activity in human
      colonic epithelial cells.
AB  - We have shown that substance P (SP) and its neurokinin-1 receptor (NK-1R)
      regulate intestinal angiogenesis by increasing expression of protein CYR61 (the
      cysteine-rich angiogenic inducer 61, or CCN1) in colonic epithelial cells.
      However, the mechanism involved in SP-induced CCN1 expression has not been
      studied, and the outcome of increased CCN1 expression in the development of
      colitis is not fully understood. Because histone deacetylase (HDAC) modulates
      transcription of several genes involved in inflammation, we investigated
      participation of HDAC in SP-induced CCN1 expression in human colonic epithelial
      NCM460 cells overexpressing NK-1R (NCM460-NK-1R) and in primary colonocytes. SP
      increased HDAC activity with deacetylation and dephosphorylation of nucleosome
      protein histone H3 in NCM460-NK-1R and/or primary colonocytes. Histone
      deacetylation and dephosphorylation was observed in colonic mucosa from irritable
      bowel disease patients. Similarly, colonic mucosal tissues from mice exposed to
      dextran sulfate sodium showed histone H3 deacetylation and dephosphorylation and
      increased HDAC activity that was reversed by the NK-1R antagonist CJ-12255. SP
      induced increased CCN1 expression in NCM460-NK-1R cells was abolished by
      pharmacological HDAC inhibition. HDAC overexpression activated basal and SP
      induced CCN1 promoter activity. Intracolonic CCN1 overexpression significantly
      ameliorated dextran sulfate sodium-induced colitis, with reduction of
      proinflammatory cytokine expression in mice. Thus, SP-mediated CCN1 expression in
      the inflamed human and mouse colon involves increased HDAC activity. Our results
      strongly suggest that increased CCN1 expression may be involved in mucosal
      healing during colitis.

PMID- 21945804
TI  - miRNA Expression profile after status epilepticus and hippocampal neuroprotection
      by targeting miR-132.
AB  - When an otherwise harmful insult to the brain is preceded by a brief,
      noninjurious stimulus, the brain becomes tolerant, and the resulting damage is
      reduced. Epileptic tolerance develops when brief seizures precede an episode of
      prolonged seizures (status epilepticus). MicroRNAs (miRNAs) are small, noncoding
      RNAs that function as post-transcriptional regulators of gene expression. We
      investigated how prior seizure preconditioning affects the miRNA response to
      status epilepticus evoked by intra-amygdalar kainic acid in mice. The miRNA was
      extracted from the ipsilateral CA3 subfield 24 hours after focal-onset status
      epilepticus in animals that had previously received either seizure
      preconditioning (tolerance) or no preconditioning (injury), and mature miRNA
      levels were measured using TaqMan low-density arrays. Expression of 21 miRNAs was
      increased, relative to control, after status epilepticus alone, and expression of
      12 miRNAs was decreased. Increased miR-132 levels were matched with increased
      binding to Argonaute-2, a constituent of the RNA-induced silencing complex. In
      tolerant animals, expression responses of >40% of the injury-group-detected
      miRNAs differed, being either unchanged relative to control or down-regulated,
      and this included miR-132. In vivo microinjection of locked nucleic acid-modified
      oligonucleotides (antagomirs) against miR-132 depleted hippocampal miR-132 levels
      and reduced seizure-induced neuronal death. Thus, our data strongly suggest that
      miRNAs are important regulators of seizure-induced neuronal death.

PMID- 21945805
TI  - Phosphorylation of podocalyxin (Ser415) Prevents RhoA and ezrin activation and
      disrupts its interaction with the actin cytoskeleton.
AB  - Podocalyxin (PC) is a polysialylated, anti-adhesin that is essential for
      maintaining foot process architecture and the integrity of the glomerular
      filtration barrier. We showed previously that PC is firmly attached to the actin
      cytoskeleton through ezrin, that in puromycin aminonucleoside (PAN)-mediated
      nephrosis the PC-ezrin-actin complex is disrupted, and that PC is uncoupled from
      actin. However, the precise mechanisms involved remained unknown. Here we show
      that detachment of PC from actin is regulated by phosphorylation of PC. PC is
      hyperphosphorylated at serines in PAN- and protamine sulfate (PS)-treated rat
      glomeruli. We determined that PC is a substrate of PKC and that the site of
      phosphorylation is Ser415, located within the juxtamembrane, ezrin-binding domain
      of the cytoplasmic tail of PC. Mutation of Ser415 to the phosphomimetic residues
      Glu (S415E) or Asp (S415D) interfered with direct binding of the PC cytoplasmic
      tail to ezrin in vitro. Moreover, stable expression of a phosphomimetic (S415E)
      PC mutant but not the WT or the phosphorylation-deficient (S415A) PC mutant,
      disrupted PC-ezrin-actin interaction, failed to activate RhoA, and the
      cytoskeletal linker, ezrin, remained inactive. Our data indicate that
      phosphorylation of PC at Ser415 prevents attachment of PC and ezrin to actin and
      highlights the strategic position of Ser415 and direct binding of PC to ezrin in
      regulating podocyte foot process architecture.

PMID- 21945806
TI  - Direction-selective patterns of activity in human visual cortex suggest common
      neural substrates for different types of motion.
AB  - A sense of motion can be elicited by the movement of both luminance- and texture
      defined patterns, what is commonly referred to as first- and second-order,
      respectively. Although there are differences in the perception of these two
      classes of motion stimuli, including differences in temporal and spatial
      sensitivity, it is debated whether common or separate direction-selective
      mechanisms are responsible for processing these two types of motion. Here, we
      measured direction-selective responses to luminance- and texture-defined motion
      in the human visual cortex by using functional MRI (fMRI) in conjunction with
      multivariate pattern analysis (MVPA). We found evidence of direction selectivity
      for both types of motion in all early visual areas (V1, V2, V3, V3A, V4, and
      MT+), implying that none of these early visual areas is specialized for
      processing a specific type of motion. More importantly, linear classifiers
      trained with cortical activity patterns to one type of motion (e.g., first-order
      motion) could reliably classify the direction of motion defined by the other type
      (e.g., second-order motion). Our results suggest that the direction-selective
      mechanisms that respond to these two types of motion share similar spatial
      distributions in the early visual cortex, consistent with the possibility that
      common mechanisms are responsible for processing both types of motion.

PMID- 21945807
TI  - On the dependency of division on multiplication: selective loss for conceptual
      knowledge of multiplication.
AB  - This study reports the case of a patient (AG) whose main calculation problem was
      with multiplication that was severely affected at all levels including that of
      conceptual knowledge. In contrast AG's problems with addition, subtraction and
      division were much less conspicuous and just involved the use of procedures. For
      all these latter operations, and for division in particular, conceptual knowledge
      was spared. Despite his procedural problems, AG in fact was fully aware that
      division consists of finding out how many times a given quantity is contained in
      another quantity. Thus while he was able to reach the correct results for
      division by subtracting the divisor from the dividend, he never used the reverse
      strategy to complete multiplication operations, i.e. add the number for as many
      times as the multiplier to complete the operation, and showed no awareness that
      this was what multiplying means, even when explicit suggestions were made by the
      examiner. The existence of AG's case could not be expected on the basis of
      theories holding that division depends on multiplication and that is not
      separately represented in semantic memory. It follows, therefore, that the extent
      to which division depends on multiplication needs to be reconsidered.

PMID- 21945809
TI  - Linoleic acid induces an EMT-like process in mammary epithelial cells MCF10A.
AB  - Epidemiological studies and animal models suggest an association between high
      levels of dietary fat intake and an increased risk of developing breast cancer.
      Epithelial-mesenchymal-transition (EMT) is a process, by which epithelial cells
      are transdifferentiated to a mesenchymal state, and it has been implicated in
      cancer progression, including invasion and metastasis. Linoleic acid (LA) induces
      proliferation and invasion in breast cancer cells. However, the role of LA on the
      EMT process in human mammary epithelial cells remains to be studied. In the
      present study, we demonstrate that LA induces a transient down-regulation of E
      cadherin expression, accompanied with an increase of Snail1, Snail2, Twist1,
      Twist2 and Sip1 expressions. Furthermore, LA induces FAK and NFkappaB activation,
      MMP-2 and -9 secretions, migration and invasion. In summary, our findings
      demonstrate, for the first time, that LA promotes an EMT-like process in MCF10A
      human mammary epithelial cells.

PMID- 21945808
TI  - Age-related neural changes in autobiographical remembering and imagining.
AB  - Numerous neuroimaging studies have revealed that in young adults, remembering the
      past and imagining the future engage a common core network. Although it has been
      observed that older adults engage a similar network during these tasks, it is
      unclear whether or not they activate this network in a similar manner to young
      adults. Young and older participants completed two autobiographical tasks
      (imagining future events and recalling past events) in addition to a semantic
      visuospatial control task. Spatiotemporal Partial Least Squares analyses examined
      whole brain patterns of activity across both the construction and elaboration of
      autobiographical events. These analyses revealed that that both age groups
      activated a similar network during the autobiographical tasks. However, some key
      age-related differences in the activation of this network emerged. During the
      construction of autobiographical events, older adults showed less activation
      relative to younger adults, in regions supporting episodic detail such as the
      medial temporal lobes and the precuneus. Later in the trial, older adults showed
      differential recruitment of medial and lateral temporal regions supporting the
      elaboration of autobiographical events, and possibly reflecting an increased role
      of conceptual information when older adults describe their pasts and their
      futures.

PMID- 21945810
TI  - Inhibitors of specific ceramide synthases.
AB  - Ceramide synthases (CerSs) are key enzymes in the biosynthesis of ceramides and
      display a group of at least six different isoenzymes (CerS1-6). Ceramides itself
      are bioactive molecules. Ceramides with different N-acyl side chains (C(14:0)-Cer
      - C(26:0)-Cer) possess distinct roles in cell signaling. Therefore, the selective
      inhibition of specific CerSs which are responsible for the formation of a
      specific ceramide holds promise for a number of new clinical treatment
      strategies, e.g., cancer. Here, we identified four of hitherto unknown functional
      inhibitors of CerSs derived from the FTY720 (Fingolimod) lead structure and
      showed their inhibitory effectiveness by two in vitro CerS activity assays.
      Additionally, we tested the substances in two cell lines (HCT-116 and HeLa) with
      different ceramide patterns. In summary, the in vitro activity assays revealed
      out that ST1058 and ST1074 preferentially inhibit CerS2 and CerS4, while ST1072
      inhibits most potently CerS4 and CerS6. Importantly, ST1060 inhibits
      predominately CerS2. First structure-activity relationships and the potential
      biological impact of these compounds are discussed.

PMID- 21945811
TI  - Ceramide 1-phosphate stimulates proliferation of C2C12 myoblasts.
AB  - Recent studies have established specific cellular functions for different
      bioactive sphingolipids in skeletal muscle cells. Ceramide 1-phosphate (C1P) is
      an important bioactive sphingolipid that has been involved in cell growth and
      survival. However its possible role in the regulation of muscle cell homeostasis
      has not been so far investigated. In this study, we show that C1P stimulates
      myoblast proliferation, as determined by measuring the incorporation of tritiated
      thymidine into DNA, and progression of the myoblasts through the cell cycle. C1P
      induced phosphorylation of glycogen synthase kinase-3beta and the product of
      retinoblastoma gene, and enhanced cyclin D1 protein levels. The mitogenic action
      of C1P also involved activation of phosphatidylinositol 3-kinase/Akt, ERK1/2 and
      the mammalian target of rapamycin. These effects of C1P were independent of
      interaction with a putative G(i)-coupled C1P receptor as pertussis toxin, which
      maintains G(i) protein in the inactive form, did not affect C1P-stimulated
      myoblast proliferation. By contrast, C1P was unable to inhibit serum starvation-
      or staurosporine-induced apoptosis in the myoblasts, and did not affect myogenic
      differentiation. Collectively, these results add up to the current knowledge on
      cell types targeted by C1P, which so far has been mainly confined to fibroblasts
      and macrophages, and extend on the mechanisms by which C1P exerts its mitogenic
      effects. Moreover, the biological activities of C1P described in this report
      establish that this phosphosphingolipid may be a relevant cue in the regulation
      of skeletal muscle regeneration, and that C1P-metabolizing enzymes might be
      important targets for developing cellular therapies for treatment of skeletal
      muscle degenerative diseases, or tissue injury.

PMID- 21945812
TI  - Monitoring of wild birds for Newcastle disease virus in north Queensland,
      Australia.
AB  - Wild aquatic birds (WABs) are considered as reservoir hosts for Newcastle disease
      viruses (NDVs) and may act as vectors for transferring these viruses to poultry,
      causing outbreaks of disease. A 3-year epidemiological study was conducted on
      WABs of north Queensland from April 2007 to March 2010. Swab and fresh moist
      faecal samples of WABs were screened to detect Newcastle disease viral (NDV) RNA
      by one-step real time reverse transcriptase polymerase chain reaction (rRT-PCR)
      in multiplex primers, targeting the matrix gene. The potential reactor samples in
      rRT-PCR were processed for sequencing of the different NDV genes using
      conventional PCR. The overall NDV RNA prevalence was 3.5% for live bird samples
      (N=1461) and 0.4% for faecal samples (N=1157). Plumed whistling ducks (PWDs) had
      a higher prevalence (4.2%) than Pacific black ducks (PBDs) (0.9%) (chi(2) test,
      p=0.001). Univariate and multivariate logistic regression analyses were used to
      estimate the association between the proportion of reactor and non-reactor NDV
      RNA samples of PWDs and potential risk factors. The odds of reactor samples were
      2.7 (95% Confidence Interval 1.5-4.9) times more likely in younger than older
      ducks (p=0.001) (data set B, multivariate analysis). Both NDV RNA class-one and
      class-two types were identified in samples of WABs (12 and 59, respectively)
      (Supplementary Table 1). Phylogenetic analysis of the matrix gene identified two
      reactor sequences of class-one type NDV RNA (PWD-48 and 55) which were closely
      related to the sequences of Australian Ibis and duck isolates (Fig. 2). Another
      reactor sample sequence was determined as class-two type NDV RNA (PWD-46,
      avirulent) based on analysis of the matrix and fusion genes which was more
      similar to the sequences of Australian I-2 progenitor virus and vaccine strain
      virus (Figs. 3 and 4). Our findings of higher prevalence in PWDs along with
      confirmation of class-one and class-two type NDV RNAs will significantly
      contribute to the design of surveillance programs for NDVs in northern Australia.

PMID- 21945813
TI  - Bovine respiratory disease: efficacy of different prophylactic treatments in veal
      calves and antimicrobial resistance of isolated Pasteurellaceae.
AB  - The present study was conducted to evaluate the efficacy of two prophylactic
      antibiotic treatments against bovine respiratory disease (BRD) in veal calves. In
      addition, the antibiotic susceptibilities of isolated Pasteurellaceae were
      tested. The calves were treated either on the day of arrival by a single
      administration of tulathromycin (group A, n=20), by a peroral administration of
      chlortetracycline, sulphadimidine, and tylosin (group B, n=20) for seven
      consecutive days, or were not prophylactically treated (group C, n=19). On the
      first day of clinically diagnosed BRD, transtracheal lavage samples were obtained
      prior to therapeutic treatment and were subsequently cultured. Pasteurellaceae
      isolates were tested for their susceptibility to 12 antimicrobial agents by the
      determination of the minimal inhibitory concentrations. During the first 56 d
      after arrival, different calves in group A and B suffered from one episode of
      clinically diagnosed BRD while calves of group C experienced two episodes. The
      average daily weight gain during the same period was significantly lower in group
      C (0.89 +/- 0.04kg/d) than in the two prophylactically treated groups (1.14 +/-
      0.05 and 1.15 +/- 0.04 kg/d for group A and B, respectively). The improved
      performance of groups A and B in comparison to group C could be related to a
      lower incidence of respiratory disorders during the first days after arrival in
      the prophylactically treated animals. No differences in the clinical efficacy
      were seen between the two tested prophylactic treatments. The most prevalent
      bacterial pathogens isolated (n=79) were Pasteurella multocida (23% of isolated
      pathogens), Mycoplasma bovis (18%), and Mannheimia varigena (16%). For the
      isolated Pasteurellaceae, a high resistance pattern was observed to tylosin (83%
      of the tested P. multocida and 88% of the Mannheimia spp. isolates resistant) and
      tilmicosin (56% of the tested P. multocida isolates non-sensitive).

PMID- 21945814
TI  - A measure of my agency?

PMID- 21945815
TI  - Suppression of FoxO1/cell death-inducing DNA fragmentation factor alpha-like
      effector A (Cidea) axis protects mouse beta-cells against palmitic acid-induced
      apoptosis.
AB  - Chronic exposure to free fatty acid (FFA) induces pancreatic beta-cell apoptosis,
      which may contribute to the development of type 2 diabetes. The cell death
      inducing DNA fragmentation factor alpha-like effector (CIDE) family is involved
      in type 2 diabetes with obesity. In the present study, we found that only
      apoptosis-inducing FFA upregulated Cidea, and both apoptosis and Cidea were
      upregulated most strongly by palmitic acid, suggesting that the expression of
      Cidea is positively correlated with apoptosis. In contrast, there were weak
      correlations between Cideb and Cidec expression, and apoptosis. Furthermore,
      suppression of Cidea inhibited palmitic acid-induced apoptosis. Finally,
      suppression of FoxO1 inhibited palmitic acid-induced Cidea upregulation and
      apoptosis. These results indicate that Cidea is a critical regulator of FFA
      induced apoptosis as a novel downstream target for FoxO1 in beta-cells,
      suggesting that suppression of Cidea is a potentially useful therapeutic approach
      for protecting against beta-cell loss in type 2 diabetes.

PMID- 21945816
TI  - A preliminary investigation of the role of melanin-concentrating hormone (MCH)
      and its receptors in appetite regulation of winter flounder (Pseudopleuronectes
      americanus).
AB  - In order to better understand the role of melanin-concentrating hormone (MCH) in
      the regulation of appetite in fish, the mRNAs of two forms of MCH, prepro-MCH and
      MCH2, and two forms of MCH receptors, MCH-R1 and MCH-R2, were isolated from
      winter flounder (Pseudopleuronectes americanus). In addition, the mRNA
      expressions of these peptides and their receptors were determined under fed and
      fasted conditions. Both MCHs are expressed in forebrain and midbrain, as well as
      peripheral tissues including gut and gonads. Both MCH-Rs are ubiquitously
      expressed in the brain and periphery. Fasting induced an increase in the
      expression levels of MCH and MCH-R1 mRNAs in optic tectum/thalamus and
      hypothalamus but had no effect on either MCH2 or MCH-R2 mRNA expressions. Our
      results suggest that MCH and MCH-R1, but not MCH2 and MCH-R2 might have a role in
      the regulation of appetite in flounder.

PMID- 21945817
TI  - Optimal developmental stage for vitrification of parthenogenetically activated
      porcine embryos.
AB  - The objective of this experiment was to determine the optimal developmental stage
      to vitrify in vitro cultured porcine parthenogenetically activated (PA) embryos.
      Embryos were vitrified by Cryotop on Day 4, 5 or 6 after oocyte activation (Day
      0), and immediately after warming they were either time-lapse monitored for 24h
      or analyzed by differential staining. After warming, the embryos had to be
      cultured for at least 8h before their survival rates were stabilized. Both the
      survival rate at 8h and the hatching rate at 24h of Day 4 embryos were
      significant higher than those vitrified on Day 5 or 6 (P<0.05), no matter if they
      were morulae or blastocysts. These results demonstrate that porcine PA embryos
      can survive successfully after vitrification/warming, that the optimal time for
      vitrification was Day 4 for both morulae and blastocysts, and that 8h after
      warming was the time needed to make an early evaluation of porcine PA embryo
      survival.

PMID- 21945818
TI  - Effects of dithioerythritol on ram semen after the freeze-thawing process.
AB  - The aim of this study was to evaluate the effects of dithioerythritol added to
      cryopreservation extender on the post-thawed sperm parameters, lipid peroxidation
      and antioxidant activities of Merino ram sperm. Semen samples from 5 mature
      Merino rams (1 and 2 years of age) were used in the study. Semen samples, which
      were diluted with a Tris-based extender containing 0.5, 1, and 2mM dithiothreitol
      and no antioxidant (control), were cooled to 5 degrees C and frozen in 0.25 ml
      French straws. Frozen straws were then thawed individually at 37 degrees C for
      20s in a water bath for evaluation. The addition of dithioerythritol at 0.5 and
      2mM doses led to higher percentages of subjective motility (62.9+/-4.2% and
      63.6+/-1.8%) compared to control (52.0+/-4.9%, P<0.05). As regards CASA motility,
      dithioerythritol 0.25 and 2 mM (60.2+/-4.5% and 59.6+/-1.2%) groups were higher
      from that of control (44.2+/-8.7%, P<0.05). For the CASA progressive motility,
      0.25, 0.5 and 2 mM doses of dithioerythritol (22.0+/-2.1%, 21.7+/-2.5% and 24.0+/
      1.2%) had increasing effect in comparison to control (15.0+/-2.5%).
      Dithioerythritol at 1 and 2 mM doses for ALH provided higher values compared to
      the control (P<0.001) following the freeze-thawing process. Supplementation with
      dithiothreitol did not significantly affect the integrities of sperm membrane and
      acrosome, and mitochondrial activities. No significant differences were observed
      in biochemical parameters among the groups (P>0.05). Findings of this study
      showed that dithioerythritol supplementation in semen extenders, was of greater
      benefit to sperm motility of frozen-thawed ram sperm.

PMID- 21945820
TI  - Associations between household income, height, and BMI in contemporary US
      schoolchildren.
AB  - This paper evaluates the association between income and physical development in a
      nationally representative sample of contemporary US schoolchildren followed from
      kindergarten to eighth grade (average ages of 6-14). A generalized linear mixed
      modeling framework is used to evaluate height and body mass index (BMI) as both
      levels and annualized growth in a pooled sample. Contemporary US schoolchildren
      show income variation in height that is significant but modest at around .1cm (in
      kindergarten) to .4cm (eighth grade) increases per doubling of income. An
      exception is found for Hispanic children who show faster height velocity
      associated with higher income through childhood yielding a 1.0cm increase per
      doubling of income by the eighth grade. All groups except black males show a
      negative relationship between income and BMI that becomes stronger with age with
      an average .8kg/m(2) lower BMI per doubling of income by the eighth grade. These
      results are robust to the inclusion of baseline anthropometric controls. The
      analysis suggests that higher-income US schoolchildren enter mid-adolescence as
      taller but with lower proportional body mass relative to their lower-income
      counterparts.

PMID- 21945819
TI  - Loading solution prevents activation damage of human platelets before
      lyophilization.
AB  - The current study aims to optimize the compositions of platelet activation
      inhibitors for a loading solution of lyophilizing protectants and to establish a
      series of perfect pretreatment methods for platelet lyophilization. The optimal
      combination of six kinds of inhibitors and loading solutions of lyophilizing
      protectants, including prostaglandin E1 (PGE1), adenosine, L-arginine,
      phyticacid, bivalirudin, and cilostazol, was analyzed using the orthogonal
      experimental design. The values of the expression rates of p-selectin (CD62p) and
      platelet membrane glycoprotein (PAC-1), as well as of platelet and mean platelet
      volume (MPV), were selected as indices of platelet activation. The values of
      CD62p and Pac-1 induced by thrombin were determined as indices of platelet
      reactivity. The maximal aggregation and slide platelet aggregation test (SPAT)
      induced by the inducer were calculated as indices of the aggregation function of
      platelets. Level I of the loading condition factor had no adverse action on MPV,
      CD62p, PAC-1, SPAT, and the maximum platelet aggregation rate. Level II of
      factors PGE1, L-arginine, phycicacid sodium, and Bivalirudin could inhibit the
      activation of platelets and enable them to retain their function. The results
      show that the optimal solution compounding was the third group. The loading
      solution, which includes plasma, 1 MUM prostaglandin E1, 5 mM L-arginine, 0.5 mM
      phyticacid, and 0.5 MUM bivalirudin, could prevent the activation damage of
      platelets before lyophilization.

PMID- 21945821
TI  - Complex transcriptional regulation of citrate metabolism in Clostridium
      perfringens.
AB  - A Gram-positive, spore-forming bacterium, Clostridium perfringens, possesses
      genes for citrate metabolism, which might play an important role in the
      utilization of citrate as a sole carbon source. In this study, we identified a
      chromosomal citCDEFX-mae-citS operon in C. perfringens strain 13, which is
      transcribed on three mRNAs of different sizes. Expression of the cit operon was
      significantly induced when 5 mM extracellular citrate was added to the growth
      medium. Most interestingly, three regulatory systems were found to be involved in
      the regulation of the expression of cit genes: 1) the two upstream divergent
      genes citG and citI; 2) two different two-component regulatory systems, CitA/CitB
      (TCS6 consisted of CPE0531/CPE0532) and TCS5 (CPE0518/CPE0519); and 3) the global
      two-component VirR/VirS-VR-RNA regulatory system known to regulate various genes
      for toxins and degradative enzymes. Our results suggest that in C. perfringens
      the citrate metabolism might be strictly controlled by a complex regulatory
      system.

PMID- 21945822
TI  - Effect of unknown relationships on linearity, steepness and rank ordering of
      dominance hierarchies: simulation studies based on data from wild monkeys.
AB  - The presence of unknown dyadic relationships is a common problem in constructing
      dominance hierarchies for groups of social animals. Although previously
      acknowledged, the influence of unknown relationships on hierarchy measures like
      linearity and steepness has not been studied in detail. Using real data-sets from
      four groups of wild monkeys, we illustrate how unknown relationships affect
      linearity and steepness of hierarchies and the consistency of rank ordering based
      on de Vries' I&SI method. Monte Carlo simulations revealed significant negative
      linear relationships between the proportion of unknown relationships and both
      linearity and steepness. These simulations over-estimated steepness and linearity
      indices relative to additional real-data input matrices. Rank orders became
      inconsistent at 26-38% unknown relationships, depending on the group. Group size
      and the specific input matrix substantially affected how much unknown
      relationships influenced steepness and linearity, the values of these indices and
      the point at which rank order became inconsistent. We recommend caution in
      characterizing the dominance structure of a group with many unknown
      relationships, and in drawing conclusions about hierarchy linearity and steepness
      based on few input matrices, especially if they contain many unknown
      relationships. Quantitative characterizations of hierarchies are perhaps best
      viewed as a somewhat fluid range rather than fixed values.

PMID- 21945823
TI  - The role of the in situ local inflammatory response in predicting recurrence and
      survival in patients with primary operable colorectal cancer.
AB  - Colorectal cancer progression and survival is dependent on complex interactions
      between the tumour and the host. The pronounced local inflammatory response in
      and around the tumour is thought to represent the in situ host anti-tumour immune
      response. Since early reports, 40 years ago, there has been a continuing interest
      in establishing the cellular composition of immune cell infiltrates and their
      relationship with survival in colorectal cancer. In this review, we
      comprehensively examine the evidence for the local inflammatory cell reaction/in
      situ immune response in predicting outcome in primary operable colorectal cancer
      and make recommendations as to how such information may be incorporated into
      routine clinical assessment. Generally, an increasing number/density of immune
      cells in and around the tumour is associated with improved outcome in over 100
      studies. Whilst the prognostic value of a generalized lymphocytic infiltrate or
      non-specific peritumoural inflammatory response is strongly related to survival
      based on 40 different studies, it is also apparent that most individual immune
      cell types relate to recurrence and cancer specific survival. The evidence is
      particularly robust for tumour infiltrating T lymphocytes and their subsets
      (CD3+, CD8+, CD45RO+, FOXP3+) in addition to tumour associated macrophages,
      dendritic cells and neutrophils. Taken together, the evidence suggests both
      adaptive and innate anti-tumour immune responses play key roles in determining
      cancer progression. In order to establish routine clinical utility there is a
      need to rationalise this prognostic information, published over a 40 years
      period, into a standardized assessment of tumour inflammatory cell infiltrate.
      Such standardization may also guide development of novel therapeutic
      interventions.

PMID- 21945824
TI  - Hepatoprotective activity of the edible snail (Bellamia bengalensis) flesh
      extract in carbon tetrachloride induced hepatotoxicity in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: In the folk-traditional medicine, snails were
      used to purify blood, boost immune system, prevent conjunctivitis and to treat
      liver problems. OBJECTIVES: To evaluate the hepatoprotective activity of the
      edible snail (Bellamia bengalensis) flesh extract in male Wistar rats treated
      with carbon tetrachloride as an hepatotoxicant. MATERIALS AND METHODS: Live adult
      Bellamia bengalensis was collected commercially from the Kolkata market. Aqueous
      flesh extract (BBE) was prepared in 0.9% saline and expressed in terms of wet
      weight basis. The aqueous flesh extract was administered orally (1, 2 g kg(
      1)day(-1)) to male rats for 12 days. Liv52 was used as positive control. 24h
      after administration of extract, the rats were given a single oral dose of CCl(4)
      (1.25 ml kg(-1)), except vehicle control rats. After 24h of CCl(4)
      administration, all the animals were sacrificed to collect the blood and liver
      tissue. RESULTS: BBE (1 and 2 g kg(-1)day(-1), p.o.*12 days) significantly
      prevented CCl(4) induced elevation of SGOT, SGPT, gammaGT, ACP, ALP, bilirubin,
      LDH and CCl(4) induced decrease in total protein, triglyceride level in male
      Wistar rats. BBE treated rat liver anti-oxidant parameters (LPO, SOD, GSH, CAT,
      GPx) were significantly antagonized for the pro-oxidant effect of CCl(4).
      Histopathological studies also supported the protective effect of BBE.
      CONCLUSION: This study validated the folk and traditional use of snail in liver
      disorder through CCl(4)-induced rat experimental model.

PMID- 21945825
TI  - A novel and simple microcontact printing technique for tacky, soft substrates
      and/or complex surfaces in soft tissue engineering.
AB  - Microcontact printing (MUCP) has attracted much interest due to its simplicity
      and wide range of applications. However, when conventional MUCP is applied to
      soft and/or tacky substrates, substrate sagging and difficulty in stamp removal
      cause non-conformance in the patterns. Moreover, it is almost impossible to apply
      conventional MUCP on complex or wavy surfaces. In this study, we developed a
      novel yet simple trans-print method to create efficient micropatterning on soft
      and/or tacky substrates such as polydimethylsiloxane and polyacrylamide gel, and
      also on curved surfaces, by introducing polyvinyl alcohol film as a trans-print
      media. This technique is simple as it only involves one trans-print step and is
      also cost-effective. Most importantly, this technique is also versatile and we
      have proven this by printing various designs on more complex non-flat surfaces
      using various proteins as inks. The quality of the trans-printed pattern was
      excellent with high reproducibility and resolution as verified by immunostaining.
      Human mesenchymal stem cells cultured on these patterns displayed good
      conformance on the soft and tacky substrates printed using this technique. These
      results suggest that this novel trans-print technique can be extended to a
      potentially generic methodology for MUCP of other proteins and biomolecules,
      other shapes and sizes, and cells, and will also be useful in three-dimensional
      micropatterning for soft tissue engineering.

PMID- 21945826
TI  - Biphasic, triphasic and multiphasic calcium orthophosphates.
AB  - Biphasic, triphasic and multiphasic (polyphasic) calcium orthophosphates have
      been sought as biomaterials for reconstruction of bone defects in maxillofacial,
      dental and orthopedic applications. In general, this concept is determined by
      advantageous balances of more stable (frequently hydroxyapatite) and more
      resorbable (typically tricalcium orthophosphates) phases of calcium
      orthophosphates, while the optimum ratios depend on the particular applications.
      Therefore, all currently known biphasic, triphasic and multiphasic formulations
      of calcium orthophosphate bioceramics are sparingly soluble in water and, thus,
      after being implanted they are gradually resorbed inside the body, releasing
      calcium and orthophosphate ions into the biological medium and, hence, seeding
      new bone formation. The available formulations have already demonstrated proven
      biocompatibility, osteoconductivity, safety and predictability in vitro, in vivo,
      as well as in clinical models. More recently, in vitro and in vivo studies have
      shown that some of them might possess osteoinductive properties. Hence, in the
      field of tissue engineering biphasic, triphasic and multiphasic calcium
      orthophosphates represent promising biomaterials to construct various scaffolds
      capable of carrying and/or modulating the behavior of cells. Furthermore, such
      scaffolds are also suitable for drug delivery applications. This review
      summarizes the available information on biphasic, triphasic and multiphasic
      calcium orthophosphates, including their biomedical applications. New
      formulations are also proposed.

PMID- 21945827
TI  - Solid-state capture and real-time analysis of individual T cell activation via
      self-assembly of binding multimeric proteins on functionalized materials
      surfaces.
AB  - Polyfunctional T cell responses are increasingly underpinning new and improved
      vaccination regimens. Studies of the nature and extent of these T cell responses
      may be facilitated if specific T cell populations can be assessed from mixed
      populations by ligand-mediated capture in a solid-state assay format.
      Accordingly, we report here the development of a novel strategy for the solid
      state capture and real-time activation analyses of individual cognate T cells
      which utilizes a spontaneous self-assembly process for generating multimers of
      biotinylated class I major histocompatibility-peptide complex (MHCp) directly on
      the solid-state assay surface while also ensuring stability by covalent
      interfacial binding. The capture surface was constructed by the fabrication of
      multilayer coatings onto standard slides. The first layer was a thin polymer
      coating with surface aldehyde groups, onto which streptavidin was covalently
      immobilized, followed by the docking of multimers of biotinylated MHCp or
      biotinylated anti-CD45.1 monoclonal antibody. The high binding strength at each
      step of this immobilization sequence aims to ensure that artefacts such as
      (partial) detachment, or displacement by proteins from solution, would not
      interfere with the intended biological assays. The multilayer coating steps were
      monitored by X-ray photoelectron spectroscopy; data indicated that the MHCp
      proteins self-assembled in a multimeric form onto the streptavidin surface.
      Immobilized multimeric MHCp demonstrated the capacity to bind and retain antigen
      specific T cells from mixed populations of cells onto the solid carrier.
      Furthermore, real-time confocal microscopic detection and quantification of
      subsequent calcium flux using paired fluorescent ratiometric probes facilitated
      the analysis of individual T cell response profiles, as well as population
      analyses using a combination of individual T cell events.

PMID- 21945829
TI  - Submicron bioactive glass tubes for bone tissue engineering.
AB  - Herein we describe a method to fabricate submicron bioactive glass tubes using
      sol-gel and coaxial electrospinning techniques for applications in bone tissue
      engineering. Heavy mineral oil and gel solution were delivered by two independent
      syringe pumps during the coaxial electrospinning process. Subsequently, submicron
      bioactive glass tubes were obtained by removal of poly(vinyl pyrrolidone) and
      heavy mineral oil via calcination at 600  degrees C for 5 h. Tubular structure
      was confirmed by scanning electron microscopy and transmission electron
      microscopy imaging. We examined the bioactivity of submicron bioactive glass
      tubes and fibers and evaluated their biocompatibility, using electrospun
      poly(epsilon-caprolactone) fibers--a bioinactive material--for comparison. The
      bioactivity of the glass tubes was examined in a simulated body fluid and they
      demonstrated the formation of hydroxyapatite-like minerals on both the outer and
      inner surfaces. In contrast, mineralization only occurred on their surface for
      bioactive glass solid fibers. Energy-dispersive X-ray data suggested that the
      bioactive glass tubes had a faster induction of mineral formation than the solid
      fibers. We demonstrate that the proliferation rate of mouse preosteoblastic MC3T3
      E1 cells on bioactive glass tubes was comparable to that on solid fibers. We also
      show that bioactive glass tubes can be loaded with a model protein drug, bovine
      serum albumin, and that these structures exhibit delayed release properties. The
      bioactivity of released lysozyme can be as high as 90.9%. Taken together, these
      data suggest that submicron bioactive glass tubes could hold great potential for
      use in bone tissue engineering as well as topical drug or gene delivery.

PMID- 21945828
TI  - Patient-derived endothelial progenitor cells improve vascular graft patency in a
      rodent model.
AB  - Late outgrowth endothelial progenitor cells (EPCs) derived from the peripheral
      blood of patients with significant coronary artery disease were sodded into the
      lumens of small diameter expanded polytetrafluoroethylene (ePTFE) vascular
      grafts. Grafts (1mm inner diameter) were denucleated and sodded either with
      native EPCs or with EPCs transfected with an adenoviral vector containing the
      gene for human thrombomodulin (EPC+AdTM). EPC+AdTM was shown to increase the in
      vitro rate of graft activated protein C (APC) production 4-fold over grafts
      sodded with untransfected EPCs (p<0.05). Unsodded control and EPC-sodded and
      EPC+AdTM-sodded grafts were implanted bilaterally into the femoral arteries of
      athymic rats for 7 or 28 days. Unsodded control grafts, both with and without
      denucleation treatment, each exhibited 7 day patency rates of 25%. Unsodded
      grafts showed extensive thrombosis and were not tested for patency over 28 days.
      In contrast, grafts sodded with untransfected EPCs or EPC+AdTM both had 7 day
      patency rates of 88-89% and 28 day patency rates of 75-88%. Intimal hyperplasia
      was observed near both the proximal and distal anastomoses in all sodded graft
      conditions but did not appear to be the primary occlusive failure event. This in
      vivo study suggests autologous EPCs derived from the peripheral blood of patients
      with coronary artery disease may improve the performance of synthetic vascular
      grafts, although no differences were observed between untransfected EPCs and TM
      transfected EPCs.

PMID- 21945830
TI  - Engineering membrane scaffolds with both physical and biomolecular signaling.
AB  - We report on the combination of a top-down and bottom-up approach to develop thin
      bioactive membrane scaffolds based on functional elastin-like polymers (ELPs).
      Our strategy combines ELP cross-linking and assembly, and a variety of standard
      and novel micro/nanofabrication techniques to create self-supporting membranes
      down to ~500 nm thick that incorporate both physical and biomolecular signals,
      which can be easily tailored for a specific application. In this study we used an
      ELP that included the cell-binding motif arginine-glycine-aspartic acid-serine
      (RGDS). Furthermore, fabrication processes were developed to create membranes
      that exhibited topographical patterns with features down to 200 nm in lateral
      dimensions and up to 10 MUm in height on either one or both sides, uniform and
      well-defined pores, or multiple ELP layers. A variety of processing parameters
      were tested in order to optimize membrane fabrication, including ELP and cross
      linker concentration, temperature, reaction time and ambient humidity. Membrane
      micro/nanopatterning, swelling and stiffness were characterized by atomic force
      microscopy, nanoindentation tests and scanning electron microscopy. Upon
      immersion in phosphate-buffered saline and an increase in temperature from 25 to
      40 degrees C, membranes exhibited a significant increase in surface stiffness,
      with the reduced Young's modulus increasing with temperature. Finally, rat
      mesenchymal stem cells were cultured on thin RGDS-containing membranes, which
      allowed cell adhesion, qualitatively enhanced spreading compared to membranes
      without RGDS epitopes and permitted proliferation. Furthermore, cell morphology
      was drastically affected by topographical patterns on the surface of the
      membranes.

PMID- 21945831
TI  - Liver fibrosis protects mice from acute hepatocellular injury.
AB  - BACKGROUND & AIMS: Development of fibrosis is part of the pathophysiologic
      process of chronic liver disease. Although it is considered deleterious, it also
      represents a form of tissue repair. Deposition of extracellular matrix changes
      the cellular environment of the liver; we investigated whether it increases
      resistance to noxious stimuli and the role of changes in intracellular signaling
      to hepatocytes in mediating this effect. METHODS: Primary cultures of mouse
      hepatocytes were exposed to type I collagen (COL1); cell injury was assessed by
      morphologic and biochemical criteria. The expression of Bcl-2 family members was
      evaluated by immunoblot analyses. Activation of extracellular signal-regulated
      kinase (ERK) was assessed using phospho-specific antibodies. Liver fibrosis was
      induced by repeated administration of thioacetamide or carbon tetrachloride to
      mice; mice were then exposed to Fas antibodies. RESULTS: Hepatocytes exposed to
      COL1 were more resistant to a variety of hepatotoxins, in a dose-dependent
      manner, and had lower levels of Bad, Bid, and Bax proapoptotic proteins compared
      with control hepatocytes. Activation of ERK1/2 was stronger and quicker in
      hepatocytes exposed to COL1. The MEK1/2 inhibitors U0126 and PD98059 reversed the
      protective effects of COL1 and the decrease in proapoptotic proteins. Hepatocytes
      isolated from ERK1(-/-) mice were insensitive to the protective effect of COL1.
      Fibrotic livers from wild-type mice had high levels of phospho-ERK1 and were
      resistant to Fas-induced cell death. ERK1(-/-) mice lost this effect.
      CONCLUSIONS: Production of COL1 during liver fibrosis induces a hepatoprotective
      response that is mediated by activation of ERK1 signaling.

PMID- 21945833
TI  - Cloning and characterisation of the SpToll gene from green mud crab, Scylla
      paramamosain.
AB  - Toll/Toll-like receptors (TLRs), one of the most important pattern recognition
      receptors (PRRs), play a crucial role in innate immune responses in both
      invertebrates and vertebrates. In this study, we cloned and characterised a Toll
      gene from Scylla paramamosain (SpToll). Bioinformatic analysis predicted that
      SpToll contained one open reading frame of 3018bp and encoded a single-pass
      transmembrane domain protein of 1005 amino acids. Further, SpToll could be
      clustered into one branch along with other arthropod Tolls in a phylogenetic
      tree. SpToll transcripts could be detected by RT-PCR from all tissues examined
      including the heart, gill, hepatopancreas, stomach, intestine, muscle, eyestalk
      and hemocytes. Infection by Vibrio parahemolyticus up-regulated SpToll mRNA
      expression in hemocytes after 48h. The profile of single nucleotide polymorphisms
      (SNPs) in the leucine-rich repeats (LRRs) domain of SpToll in three healthy crabs
      was then evaluated. Two hundred and twenty SNPs with a frequency of about 1.0
      4.0% were identified in hemocyte DNA/cDNA. Surprisingly, the adenine to guanine
      transition at position 1372 (c.1372A>G) had a frequency of about 50%. Finally,
      the results showed that challenge with V. parahemolyticus stimulated the
      appearance of two sets of SNPs in crabs. More importantly, the c.1372A>G mutation
      could contribute to a low mortality after V. parahemolyticus infection and
      introduce variation of charge and secondary structure into the SpToll
      polypeptide. In summary, these studies suggested a novel Toll homologue in crab
      and identified a SNP with potential pathogen-resistant activities. The result
      will be important for the investigation of crab immune defense mechanisms.

PMID- 21945832
TI  - Compatibility polymorphism in snail/schistosome interactions: From field to
      theory to molecular mechanisms.
AB  - Coevolutionary dynamics in host-parasite interactions potentially lead to an arms
      race that results in compatibility polymorphism. The mechanisms underlying
      compatibility have remained largely unknown in the interactions between the snail
      Biomphalaria glabrata and Schistosoma mansoni, one of the agents of human
      schistosomiasis. This review presents a combination of data obtained from field
      and laboratory studies arguing in favor of a matching phenotype model to explain
      compatibility polymorphism. Investigations focused on the molecular determinants
      of compatibility have revealed two repertoires of polymorphic and/or diversified
      molecules that have been shown to interact: the parasite antigens S. mansoni
      polymorphic mucins and the B. glabrata fibrinogen-related proteins immune
      receptors. We hypothesize their interactions define the compatible/incompatible
      status of a specific snail/schistosome combination. This line of thought suggests
      concrete approaches amenable to testing in field-oriented studies attempting to
      control schistosomiasis by disrupting schistosome-snail compatibility.

PMID- 21945834
TI  - Activation of the Caenorhabditis elegans FOXO family transcription factor DAF-16
      by pathogenic Bacillus thuringiensis.
AB  - The FOXO family of transcription factors have recently been implicated in innate
      immunity, especially in case of DAF-16 from the nematode Caenorhabditis elegans.
      However, previous studies with this nematode proposed that DAF-16 is not directly
      activated by pathogens. Rather, DAF-16 mediates resistance if activated by some
      other cue as part of a general stress response. We specifically tested this
      notion by analysis of DAF-16 nuclear translocation and thus regulatory activity
      upon exposure to pathogenic Bacillus thuringiensis. Our results demonstrate that
      DAF-16 nuclear translocation is indeed particularly induced in response to
      bacterial pathogenicity, whereas infection load alone has little effect.
      Translocation is strongest at an early time point, suggesting a role during the
      immediate immune response. The increased DAF-16 availability is associated with
      higher resistance and a reduction in feeding behaviour. Taken together, our data
      highlight that a FOXO transcription factor directly responds to pathogens and
      thus contributes to immune defence.

PMID- 21945836
TI  - Remodeling of the neuronal circuits underlying opiate-withdrawal memories
      following remote retrieval.
AB  - Several types of memory display time-dependent reorganization of their underlying
      neural substrates, but it remains unclear whether affective memories associated
      with drug effects also follow similar reorganization. Here, we analyzed the
      neural circuits reactivated by the re-exposure of former dependent rats to the
      withdrawal-paired environment 1month after conditioning (remote memory) as
      compared with recent memory (Frenois, F., Stinus, L., Di Blasi, F., Cador, M., &
      Le Moine, C. (2005) A specific limbic circuit underlies opiate withdrawal
      memories The Journal of Neuroscience, 25, 1366-1374). C-fos expression showed
      that the circuits involved in the retrieval of withdrawal memories are partly
      different when comparing recent and remote reactivation, showing that, like other
      type of memories, affective memories linked to opiate withdrawal undergo
      anatomical reorganization, with a shift from extended amygdala regions toward
      cortical areas.

PMID- 21945838
TI  - Early adolescence and suicidal ideations in Croatia: sociodemographic,
      behavioral, and psychometric correlates.
AB  - BACKGROUND/AIMS: Suicidal ideations (SI) indicate and predict psychological
      distress. We examined the prevalence of SI among early adolescents and its
      association with parental war participation, personal, behavioral, and
      sociodemographic characteristics. METHODS: We performed a cross-sectional
      questionnaire study on 803 12-year-old adolescents. Data were collected using a
      sociodemographic questionnaire, the Junior Eysenck Personality Questionnaire and
      Children Depression Inventory. Unintentional injuries, physical fighting, and
      involvement in bullying behavior were assessed using questions from the World
      Health Organization (WHO) survey Health Behavior in School-aged Children.
      Suicidal ideations were assessed with three dichotomous items. RESULTS: There
      were no gender differences in SI prevalence. SI in males were associated with
      lower maternal education, crowded families, birth order, parental war
      participation, physical fighting, being bullied, and substance use. In females,
      we found associations with lower parental educational level, number of brothers,
      lower perception of the relationship with parents, parental relationship, family
      cohesion and parental control, negative attitude toward school, rare church
      attendance, fighting, and being bully or bullied. Depressive symptoms and SI were
      associated in both genders. CONCLUSIONS: SI showed gender-specific associations
      that may partially be explained with parental war involvement. These findings may
      have potentially important clinical and preventive implications.

PMID- 21945835
TI  - The role of the basal ganglia in learning and memory: insight from Parkinson's
      disease.
AB  - It has long been known that memory is not a single process. Rather, there are
      different kinds of memory that are supported by distinct neural systems. This
      idea stemmed from early findings of dissociable patterns of memory impairments in
      patients with selective damage to different brain regions. These studies
      highlighted the role of the basal ganglia in non-declarative memory, such as
      procedural or habit learning, contrasting it with the known role of the medial
      temporal lobes in declarative memory. In recent years, major advances across
      multiple areas of neuroscience have revealed an important role for the basal
      ganglia in motivation and decision making. These findings have led to new
      discoveries about the role of the basal ganglia in learning and highlighted the
      essential role of dopamine in specific forms of learning. Here we review these
      recent advances with an emphasis on novel discoveries from studies of learning in
      patients with Parkinson's disease. We discuss how these findings promote the
      development of current theories away from accounts that emphasize the
      verbalizability of the contents of memory and towards a focus on the specific
      computations carried out by distinct brain regions. Finally, we discuss new
      challenges that arise in the face of accumulating evidence for dynamic and
      interconnected memory systems that jointly contribute to learning.

PMID- 21945841
TI  - The integrated motivational-volitional model of suicidal behavior.

PMID- 21945840
TI  - Best practice elements of multilevel suicide prevention strategies: a review of
      systematic reviews.
AB  - BACKGROUND: Evidence-based best practices for incorporation into an optimal
      multilevel intervention for suicide prevention should be identifiable in the
      literature. AIMS: To identify effective interventions for the prevention of
      suicidal behavior. METHODS: Review of systematic reviews found in the Pubmed,
      Cochrane, and DARE databases. Steps include risk-of-bias assessment, data
      extraction, summarization of best practices, and identification of synergistic
      potentials of such practices in multilevel approaches. RESULTS: Six relevant
      systematic reviews were found. Best practices identified as effective were as
      follows: training general practitioners (GPs) to recognize and treat depression
      and suicidality, improving accessibility of care for at-risk people, and
      restricting access to means of suicide. Although no outcomes were reported for
      multilevel interventions or for synergistic effects of multiple interventions
      applied together, indirect support was found for possible synergies in particular
      combinations of interventions within multilevel strategies. CONCLUSIONS: A number
      of evidence-based best practices for the prevention of suicide and suicide
      attempts were identified. Research is needed on the nature and extent of
      potential synergistic effects of various preventive activities within multilevel
      interventions.

PMID- 21945843
TI  - Indepth interviews with 244 female suicide attempters and their associates in
      northern China: understanding the process and causes of the attempt.
AB  - BACKGROUND: Attempted suicide, a deliberate self-directed behavior situated
      within the unique social world of an individual, is a major risk factor for
      suicide. Efforts aimed at addressing female suicide must be based on
      understanding their perceived causes and the meaning of this behavior. AIMS: This
      study describes the perceived causes of suicidal behaviors to determine
      preventive measures of female suicide in China. METHODS: An in-depth interview
      about the process and causes of suicidal behavior as well as a detailed
      structured and a standardized diagnostic interview were administered to 244
      female attempters treated at general hospitals and, separately, to their
      relatives. RESULTS: The perceived three most frequent causes of the attempts were
      interpersonal conflict (87%), psychological problems (33%), and conflict between
      others that affected the subject (27%). On average 2.2 causes were identified for
      each case. The identification in the in-depth interviews of psychological
      problems as a cause of the attempt was concordant with the results of the
      independent psychiatric exam identifying a current DSM-IV mental disorder in 38%
      of cases (Kappa=0.64). CONCLUSIONS: Preventive measures of improving
      interpersonal and problem-solving skills should be developed and assessed for
      addressing female suicide in China besides expansion of psychiatric services.

PMID- 21945842
TI  - Perception of health, suicidal ideation, and suicide attempt among adults in the
      community.
AB  - BACKGROUND: There is a well-known association between perception of poor physical
      health and higher rates of physical and psychological morbidity. However, little
      is known about the possible link between perception of health and suicidality.
      AIMS: The study examines the relationship between perception of poor health and
      suicidal ideation and suicide attempt among adults in the community. METHODS:
      Data were drawn from the National Comorbidity Survey (n = 5,877), a
      representative sample of individuals 15-54 years of age in the United States.
      Multiple logistic regression analyses were used to determine the relationship
      between perception of poor health and the likelihood of suicidal ideation and
      suicide attempt. Sociodemographic characteristics, comorbid mental disorders, and
      physical illnesses were adjusted for in the final model. RESULTS: Perception of
      poor health was associated with a significantly increased likelihood of suicidal
      ideation (OR = 2.14 (1.36, 3.35) and suicide attempt (OR = 2.03 (1.06, 3.91)),
      which persisted after adjusting for differences in sociodemographic
      characteristics, mental disorders, and self-reported physical illnesses.
      CONCLUSIONS: Our findings provide initial evidence that perception of poor health
      is associated with a significantly increased likelihood of suicidal ideation and
      suicide attempt among adults in the community.

PMID- 21945844
TI  - Ethical issues relevant to the assessment of suicide risk in nonclinical research
      settings.
AB  - BACKGROUND: Our laboratory recently confronted this issue while conducting
      research with undergraduate students at the University of Waterloo (UW). Although
      our main objective was to examine cognitive and genetic features of individuals
      with schizotypal personality disorder (SPD), the study protocol also entailed the
      completion of various self-report measures to identify participants deemed at
      increased risk for suicide. AIMS AND METHODS: This paper seeks to review and
      discuss the relevant ethical guidelines and legislation that bear upon a
      psychologist's obligation to further assess and intervene when research
      participants reveal that they are at increased risk for suicide. RESULTS AND
      CONCLUSIONS: In the current paper we argue that psychologists are ethically
      impelled to assess and appropriately intervene in cases of suicide risk, even
      when such risk is revealed within a research context. We also discuss how any
      such obligation may potentially be modulated by the research participant's
      expectations of the role of a psychologist, within such a context. Although the
      focus of the current paper is on the ethical obligations of psychologists,
      specifically those practicing within Canada, the relevance of this paper extends
      to all regulated health professionals conducting research in nonclinical
      settings.

PMID- 21945845
TI  - Railway suicide in Belgium 1998-2009: incidence and prevention.
AB  - BACKGROUND: Belgium is a country with a high suicide rate (19.1/100,000 in 2004),
      and railway suicide poses a substantial safety and public health problem. This
      problem was addressed by the Suicide Prevention Unit of Infrabel (Manager of the
      Belgian Railway Infrastructure), which collects relevant data and implements a
      prevention program. AIMS: To present data on fatal and nonfatal suicidal behavior
      on the Belgian railway network, including monthly and regional distribution and
      identification of hotspots; and to present the Infrabel suicide prevention
      program. METHODS: Analysis of Infrabel data on railway suicide (1998-2009) and
      comparison with data on suicide in Belgium. RESULTS: A total of 1,092 railway
      suicides (1998-2009) and 557 suicide attempts (2003-2009) in Belgium (fatality
      rate of 54%) were studied. Monthly fluctuations were observed, with the majority
      of suicides occurring in Flanders, followed by Wallonia and Brussels. We
      identified 34 hotspots accounting for 35% of cases, mostly in Flanders.
      CONCLUSIONS: In 2004 railway suicide accounted for 5.3% of all suicides in
      Belgium (railway suicide rate of 1.03/100,000). Such a major human and economic
      loss warrants implementation of prevention measures. Infrabel has initiated a
      comprehensive suicide prevention program which focuses mainly on safeguarding the
      suicide hotspots.

PMID- 21945846
TI  - Using drug-excipient interactions for siRNA delivery.
AB  - SiRNA is the trigger of RNA interference, a mechanism discovered in the late
      1990s. To release the therapeutic potential of this versatile but large and
      fragile molecule, excipients are used which either interact by electrostatic
      interaction, passively encapsulate siRNA or are covalently attached to enable
      specific and safe delivery of the drug substance. Controlling the delicate
      balance between protective complexation and release of siRNA at the right point
      and time is done by understanding excipients-siRNA interactions. These can be
      lipids, polymers such as PEI, PLGA, Chitosans, Cyclodextrins, as well as aptamers
      and peptides. This review describes the mechanisms of interaction of the most
      commonly used siRNA delivery vehicles, and looks at the results of their clinical
      and preclinical studies.

PMID- 21945847
TI  - Cutaneous hypersensitivity test to evaluate phage display anti-tick borne vaccine
      antigen candidates.
AB  - Early experiments performed by our group with the phage display technique
      revealed the potential for using epitope-displaying phages (mimotopes) as a tool
      for tick antigen discovery. Thus, as a preliminary study, inflammatory reactions
      induced by phage display tick-borne candidates were investigated by using the
      cutaneous hypersensitivity test. The profile of selected Rhipicephalus microplus
      mimotopes was assessed on tick field-exposed cattle and our data indicated a
      pattern similar to immediate hypersensitivity reaction and not a delayed immune
      response as expected. However, the wild-type phage inoculation surprisingly
      induced a strong immediate response on its own. Such reactions indicate that the
      wild-type phage may have hidden many of the potential reactions raised by the
      mimotopes. The study of the inflammatory reactions to these phage mimotopes in
      tick-infested hosts may provide basic information about the immune reaction.
      Finally, this work is of relevance for when considering research alternatives for
      finding and characterization of antigens by the phage display technique.

PMID- 21945848
TI  - The revival of fosfomycin.
AB  - Fosfomycin, originally named phosphonomycin, was discovered in Spain in 1969.
      There are three forms of fosfomycin: fosfomycin tromethamine (a soluble salt) and
      fosfomycin calcium for oral use, and fosfomycin disodium for intravenous use.
      Fosfomycin is a bactericidal antibiotic that interferes with cell wall synthesis
      in both Gram-positive and Gram-negative bacteria by inhibiting the initial step
      involving phosphoenolpyruvate synthetase. It has a broad spectrum of activity
      against a wide range of Gram-positive and Gram-negative bacteria. It is highly
      active against Gram-positive pathogens such as Staphylococcus aureus and
      Enterococcus, and against Gram-negative bacteria such as Pseudomonas aeruginosa
      and Klebsiella pneumoniae. Its unique mechanism of action may provide a
      synergistic effect to other classes of antibiotics including beta-lactams,
      aminoglycosides, and fluoroquinolones. Oral fosfomycin is mainly used in the
      treatment of urinary tract infections, particularly those caused by Escherichia
      coli and Enterococcus faecalis. Intravenous fosfomycin has been administered in
      combination with other antibiotics for the treatment of nosocomial infections due
      to multidrug-resistant (MDR) Gram-positive and Gram-negative bacteria. Fosfomycin
      has good distribution into tissues, achieving clinically relevant concentrations
      in serum, kidneys, bladder wall, prostate, lungs, inflamed tissues, bone,
      cerebrospinal fluid, abscess fluid, and heart valves. Fosfomycin is well
      tolerated, with a low incidence of adverse events. Further randomized controlled
      trials are needed in order to evaluate the efficacy of intravenous fosfomycin for
      the management of nosocomial infections due to MDR pathogens.

PMID- 21945849
TI  - Abeta Deposition in aging is associated with increases in brain activation during
      successful memory encoding.
AB  - To investigate early effects of beta-amyloid (Abeta) on neuronal function,
      elderly normal controls (NCs, age range 58-97) were scanned with Pittsburgh
      Compound-B (PIB) positron emission tomography (a measure of Abeta) as well as
      functional magnetic resonance imaging (a measure of brain activation) while
      performing an episodic memory-encoding task of natural scenes (also performed by
      young NCs; age range 18-30). Relationships between Abeta and activation were
      assessed across task-positive (regions that activate for subsequently remembered
      vs. forgotten scenes) and task-negative regions (regions that deactivate for
      subsequently remembered vs. forgotten scenes). Significant task-related
      activation was present in a distributed network spanning ventrolateral
      prefrontal, lateral occipital, lateral parietal, posterior inferior temporal
      cortices, and the right parahippocampal/hippocampus, whereas deactivation was
      present in many default mode network regions (posteromedial, medial prefrontal,
      and lateral temporoparietal cortices). Task-positive activation was higher in
      PIB+ compared with PIB- subjects, and this activation was positively correlated
      with memory measures in PIB+ subjects. Although task deactivation was not
      impaired in PIB+ NCs, deactivation was reduced in old versus young subjects and
      was correlated with worse task memory performance among old subjects. Overall,
      these results suggest that heightened activation during episodic memory encoding
      is present in NC elderly subjects with high Abeta.

PMID- 21945850
TI  - Lexical and syntactic representations in the brain: an fMRI investigation with
      multi-voxel pattern analyses.
AB  - Work in theoretical linguistics and psycholinguistics suggests that human
      linguistic knowledge forms a continuum between individual lexical items and
      abstract syntactic representations, with most linguistic representations falling
      between the two extremes and taking the form of lexical items stored together
      with the syntactic/semantic contexts in which they frequently occur. Neuroimaging
      evidence further suggests that no brain region is selectively sensitive to only
      lexical information or only syntactic information. Instead, all the key brain
      regions that support high-level linguistic processing have been implicated in
      both lexical and syntactic processing, suggesting that our linguistic knowledge
      is plausibly represented in a distributed fashion in these brain regions. Given
      this distributed nature of linguistic representations, multi-voxel pattern
      analyses (MVPAs) can help uncover important functional properties of the language
      system. In the current study we use MVPAs to ask two questions: (1) Do language
      brain regions differ in how robustly they represent lexical vs. syntactic
      information? and (2) Do any of the language bran regions distinguish between
      "pure" lexical information (lists of words) and "pure" abstract syntactic
      information (jabberwocky sentences) in the pattern of activity? We show that
      lexical information is represented more robustly than syntactic information
      across many language regions (with no language region showing the opposite
      pattern), as evidenced by a better discrimination between conditions that differ
      along the lexical dimension (sentences vs. jabberwocky, and word lists vs.
      nonword lists) than between conditions that differ along the syntactic dimension
      (sentences vs. word lists, and jabberwocky vs. nonword lists). This result
      suggests that lexical information may play a more critical role than syntax in
      the representation of linguistic meaning. We also show that several language
      regions reliably discriminate between "pure" lexical information and "pure"
      abstract syntactic information in their patterns of neural activity.

PMID- 21945851
TI  - The association of magnetic resonance imaging (MRI)-detected structural pathology
      of the knee with crepitus in a population-based cohort with knee pain: the MoDEKO
      study.
AB  - Osteoarthritis (OA) is the most common arthropathy of the knee joint(1). Symptoms
      reported by patients and signs noted during physical examination guide clinicians
      in identifying subjects with knee OA(2-4). Pain is one of the most important
      symptoms reported by subjects with knee OA(2,3). Although very common, pain is a
      non-specific symptom, related to pathology in several structures within the knee
      joint, and includes synovitis(5), subchondral bone marrow lesions(6), and joint
      effusion(7). Further, pain is a subjective symptom that cannot be directly
      measured or assessed during physical examination. Crepitus or crepitation in
      association with arthritis is defined as a crackling or grinding sound on joint
      movement with a sensation in the joint. Crepitus may occur with or without pain
      and is a common finding during physical examination in subjects with knee OA(2
      4,8,9). It is not known whether crepitus is related to pathology in various
      structures within the knee. The aim of our study was to determine the cross
      sectional associations of structural pathologies within the knee with crepitus in
      a population-based cohort with knee pain, using magnetic resonance imaging (MRI).
      Subjects with knee pain were recruited as a random population sample, with
      crepitus assessed in each compartment of the knee using a validated and
      standardized approach during physical examination(10). MRI of the knee was
      performed to assess cartilage morphology, meniscal morphology, osteophytes,
      cruciate ligaments, and collateral ligaments. For both compartment-specific and
      whole-knee analyses, a multiple logistic regression analysis was performed to
      assess the associations of MRI-detected structural pathology with crepitus,
      adjusting for potential confounders. Variables were selected by backwards
      elimination within each compartment and in the overall knee models, and only
      statistically significant variables remained in the "selected" models; remaining
      variables in these models are adjusted for each other. An increased risk for
      compartment-specific crepitus was associated with osteophytes at the
      patellofemoral (PF) and lateral tibiofemoral (LTF) joints. Crepitus was
      associated with osteophytes and medial collateral ligament (MCL) pathology at the
      medial tibiofemoral (MTF) compartment, but cartilage damage was negatively
      associated with crepitus at this compartment. In the selected whole-knee model,
      only meniscal tears were associated with an increased risk for general crepitus.
      Thus, it seems that crepitus may be associated with pathology in several internal
      structures.

PMID- 21945853
TI  - Knockdown of RAGE expression inhibits colorectal cancer cell invasion and
      suppresses angiogenesis in vitro and in vivo.
AB  - The receptor for advanced glycation end-products (RAGE) is a transmembrane
      receptor in cells, and the interaction of RAGE with ligands results in pro
      inflammatory gene activation. Aberrant RAGE activation was reported to promote
      the pathogenesis of colorectal cancer. This study aimed to investigate the
      effects of RAGE on the regulation of cell viability, invasion, and angiogenesis,
      as well as the underlying molecular mechanisms regulating these interactions in
      colorectal cancer cells. The RAGE mRNA and protein were evaluated in five
      colorectal cancer cell lines and in 45 cases of colorectal cancer tissue
      specimens (using immuohistochemistry). RAGE expression was then knockdown using
      RAGE shRNA for assessing cell viability and invasion assays as well as for tube
      formation and CAM assays in human umbilical vein endothelial cells and chick
      embryos, respectively. RAGE was highly expressed in colorectal cancer tissues,
      and was associated with increased microvessel density. Two of the four RAGE shRNA
      constructs were able to significantly knockdown RAGE expression in SW480 cells.
      RAGE knockdown inhibited invasion capacity of SW480 cells, but did not
      significantly affect cell viability. Furthermore, the conditioned growth medium
      from stable RAGE shRNA-transfected cells suppressed tube formation of human
      umbilical vein endothelial cells and angiogenesis of chicken embryos. Knockdown
      of RAGE inhibited expression of VEGF and SP1 protein in colorectal cancer cells.
      In summary, these data suggest that silence of RAGE expression could effectively
      inhibit colorectal cancer angiogenesis in vitro and in vivo.

PMID- 21945852
TI  - Chk2-mediated G2/M cell cycle arrest maintains radiation resistance in malignant
      meningioma cells.
AB  - In continuation to our studies on radioresistance in meningioma, here we show
      that radiation treatment (7Gy) induces G2/M cell cycle arrest in meningioma
      cells. Phosphorylation of Chk2, Cdc25c and Cdc2 were found to be key events since
      interference with Chk2 activation and cyclin B1/Cdc2 interaction led to permanent
      arrest followed by apoptosis. Irradiated cells showed recovery and formed
      aggressive intracranial tumors with rapid spread and morbidity. Nevertheless,
      knock down of uPAR with or without radiation induced permanent arrest in G2/M
      phase and subsequent apoptosis in vitro and in vivo. In conclusion, our data
      suggest that combination treatment with radiation and uPAR knock down or other
      inhibitors resulting in non-reversible G2/M arrest may be beneficial in the
      management of meningiomas.

PMID- 21945854
TI  - Differential affinity of BsSCO for Cu(II) and Cu(I) suggests a redox role in
      copper transfer to the Cu(A) center of cytochrome c oxidase.
AB  - SCO (synthesis of cytochrome c oxidase) proteins are involved in the assembly of
      the respiratory chain enzyme cytochrome c oxidase acting to assist in the
      assembly of the Cu(A) center contained within subunit II of the oxidase complex.
      The Cu(A) center receives electrons from the reductive substrate ferrocytochrome
      c, and passes them on to the cytochrome a center. Cytochrome a feeds electrons to
      the oxygen reaction site composed of cytochrome a(3) and Cu(B). Cu(A) consists of
      two copper ions positioned within bonding distance and ligated by two histidine
      side chains, one methionine, a backbone carbonyl and two bridging cysteine
      residues. The complex structure and redox capacity of Cu(A) present a potential
      assembly challenge. SCO proteins are members of the thioredoxin family which led
      to the early suggestion of a disulfide exchange function for SCO in Cu(A)
      assembly, whereas the copper binding capacity of the Bacillus subtilis version of
      SCO (i.e., BsSCO) suggests a direct role for SCO proteins in copper transfer. We
      have characterized redox and copper exchange properties of apo- and metalated
      BsSCO. The release of copper (II) from its complex with BsSCO is best achieved by
      reducing it to Cu(I). We propose a mechanism involving both disulfide and copper
      exchange between BsSCO and the apo-Cu(A) site. This article is part of a Special
      Issue entitled: Biogenesis/Assembly of Respiratory Enzyme Complexes.

PMID- 21945857
TI  - Radiation therapy with unflattened photon beams: dosimetric accuracy of advanced
      dose calculation algorithms.
AB  - PURPOSE: To compare the dosimetric accuracy of advanced dose calculation
      algorithms for flattened (FF) and unflattened (FFF) photon beams. MATERIAL AND
      METHODS: We compared the enhanced collapsed cone (eCC) algorithm implemented in
      OncentraMasterplan and the XVMC (MC) code in Monaco. Test plans were created for
      10MV FF and FFF beams. Single beam tests were delivered to radiochromic films
      positioned within a solid water phantom and evaluated with 1D gamma-index
      analysis. Conformal plans were verified with ion chambers in an anthropomorphic
      thorax phantom. IMRT plans were applied to the Delta4 system and evaluated with
      gamma-criteria of 3% and 3mm. RESULTS: 1D gamma-index evaluation revealed
      significantly lower (p<0.05) average gamma(mean)-values of 0.46+/-0.22 for MC
      calculated FFF profiles compared to average values of 0.53+/-0.27 detected for FF
      beams. Respective values for eCC were 0.42+/-0.27/0.38+/-0.26 (FF/FFF). When
      considering off-axis profiles separately, we found significantly reduced average
      gamma(mean)-values for FFF and both algorithms (MC: 0.55+/-24 vs. 0.45+/-0.21,
      eCC: 0.41+/-0.24 vs. 0.35+/-0.22). No significant differences were detected on
      axis. Absolute dosimetry in the anthropomorphic phantom revealed superior results
      for MC based dose calculation, with mean deviations of 0.8+/-0.8/0.0+/-1.0%
      compared to -0.1+/-1.7/-0.5+/-0.1.7% (FF/FFF) for the eCC algorithm. IMRT plans
      showed similar results for both linac modes. CONCLUSIONS: The dose calculation
      accuracy for unflattened beams was found to be at least as high as for flattened
      beams. The slightly improved dose calculation accuracy observed for off-axis
      profiles for single FFF beams did not directly translate into better verification
      results for composite IMRT plans.

PMID- 21945855
TI  - Thiol redox requirements and substrate specificities of recombinant cytochrome c
      assembly systems II and III.
AB  - The reconstitution of biosynthetic pathways from heterologous hosts can help
      define the minimal genetic requirements for pathway function and facilitate
      detailed mechanistic studies. Each of the three pathways for the assembly of
      cytochrome c in nature (called systems I, II, and III) has been shown to function
      recombinantly in Escherichia coli, covalently attaching heme to the cysteine
      residues of a CXXCH motif of a c-type cytochrome. However, recombinant systems I
      (CcmABCDEFGH) and II (CcsBA) function in the E. coli periplasm, while recombinant
      system III (CCHL) attaches heme to its cognate receptor in the cytoplasm of E.
      coli, which makes direct comparisons between the three systems difficult. Here we
      show that the human CCHL (with a secretion signal) attaches heme to the human
      cytochrome c (with a signal sequence) in the E. coli periplasm, which is
      bioenergetically (p-side) analogous to the mitochondrial intermembrane space. The
      human CCHL is specific for the human cytochrome c, whereas recombinant system II
      can attach heme to multiple non-cognate c-type cytochromes (possessing the CXXCH
      motif.) We also show that the recombinant periplasmic systems II and III use
      components of the natural E. coli periplasmic DsbC/DsbD thiol-reduction pathway.
      This article is part of a Special Issue entitled: Biogenesis/Assembly of
      Respiratory Enzyme Complexes.

PMID- 21945856
TI  - Role of Surf1 in heme recruitment for bacterial COX biogenesis.
AB  - Biogenesis of the mitochondrial cytochrome c oxidase (COX) is a highly complex
      process involving subunits encoded both in the nuclear and the organellar genome;
      in addition, a large number of assembly factors participate in this process. The
      soil bacterium Paracoccus denitrificans is an interesting alternative model for
      the study of COX biogenesis events because the number of chaperones involved is
      restricted to an essential set acting in the metal centre formation of oxidase,
      and the high degree of sequence homology suggests the same basic mechanisms
      during early COX assembly. Over the last years, studies on the P. denitrificans
      Surf1 protein shed some light on this important assembly factor as a heme a
      binding protein associated with Leigh syndrome in humans. Here, we summarise our
      current knowledge about Surf1 and its role in heme a incorporation events during
      bacterial COX biogenesis. This article is part of a Special Issue entitled:
      Biogenesis/Assembly of Respiratory Enzyme Complexes.

PMID- 21945858
TI  - Experimental small field 6 MV output ratio analysis for various diode detector
      and accelerator combinations.
AB  - BACKGROUND AND PURPOSE: The goal of this work was to measure 6MV small field,
      detector specific, output ratios (OR(det)) using the IBA stereotactic field diode
      (SFD) and the PTW T60008, T60012, T60016 and T60017 field diodes on both Varian
      iX and Elekta Synergy accelerators, to establish estimates for the experimental
      uncertainty and characterize the measurement precision under various conditions.
      MATERIALS AND METHODS: Data were acquired at depths of 1.5, 5.0 and 10.0 cm for
      square field sizes of 3.0, 1.0, 0.9, 0.8, 0.7, 0.6 and 0.5 cm. Three isocentric
      measurements comprised of five readings were made to calculate an experimental
      output ratio OR(det) with respect to a field size of 5.0 cm. The coefficient of
      variation (CV) was calculated to characterize the precision associated with each
      detector-linac combination. Another measurement set was made to investigate the
      influence of jaw position accuracy. RESULTS: As expected for field sizes smaller
      than 3.0 cm, the measured OR(det) were not consistent across all detectors. The
      standard percent uncertainty in measured OR(det) was found to be nearly
      consistent across all detector-linac combinations: less than +/-0.25% for the 3.0
      cm field size, increasing to approximately +/-1.25% for the smallest field sizes.
      As the field size was reduced to 0.5 cm the CV increased to 0.10% and 0.15% on
      the Varian and Elekta linacs, respectively. CONCLUSION: Experimental small field
      OR(det) measured with the diode detectors used in this study are reproducible to
      within +/-1.25% (standard uncertainty), with the precision of any one set of
      measurements can be characterized with a CV between 0.10% and 0.15%.

PMID- 21945860
TI  - A challenging drug development process in the era of personalized medicine.
AB  - After years of hesitation a larger number of pharmaceutical and biotech companies
      are now supporting the idea of a more individualized pharmacotherapy. The
      companies that are now involved in this research-demanding area will have to face
      several challenges. The key factor for success will be an in-depth molecular
      understanding of the pathophysiology and the mechanism of the drug under
      development. The one-disease-one-drug-one-target paradigm that has been
      prevailing for decades is history. Most diseases are heterogeneous and based on
      molecular profiling they can be divided into biological subgroups that each
      requires a specific pharmacological intervention.

PMID- 21945859
TI  - Epigenetic mechanisms in developmental programming of adult disease.
AB  - Adverse insults during intrauterine life can result in permanent changes in the
      physiology and metabolism of the offspring, which in turn leads to an increased
      risk of disease in adulthood. This is an adaptational response by the fetus to
      changes in the environmental signals that it receives during early life to ensure
      its survival and prepare itself for postnatal life. Increasing evidence suggests
      that the epigenetic regulation of gene expression patterns has a crucial role in
      the developmental programming of adult disease. This review summarizes recent
      studies of epigenetic mechanisms and focuses particularly on studies that explore
      identifiable epigenetic biomarkers in the promoters of specific disease
      associated genes. Such biomarkers would enable early recognition of children who
      might be at risk of developing adult disease with fetal origins.

PMID- 21945861
TI  - What makes a good drug target?
AB  - Novel therapeutics in areas with a high unmet medical need are based on
      innovative drug targets. Although 'biologicals' have enlarged the space of
      druggable molecules, the number of appropriate drug targets is still limited.
      Discovering and assessing the potential therapeutic benefit of a drug target is
      based not only on experimental, mechanistic and pharmacological studies but also
      on a theoretical molecular druggability assessment, an early evaluation of
      potential side effects and considerations regarding opportunities for
      commercialization. This article defines key properties of a good drug target from
      the perspective of a pharmaceutical company.

PMID- 21945862
TI  - The vascular origin of hematopoietic cells.
AB  - More than a century ago, several embryologists described sites of hematopoietic
      activity in the vascular wall of mid-gestation vertebrate embryos, and postulated
      the transient existence of a blood generating endothelium during ontogeny. This
      hypothesis gained significant attention in the 1970s when orthotopic
      transplantation experiments between quail and chick embryos revealed specific
      vascular areas as the site of the origin of definitive hematopoiesis. However,
      the vascular origin of hematopoietic precursors remained elusive and
      controversial for decades. Only recently, multiple experimental approaches have
      clearly documented that during vertebrate development definitive hematopoietic
      precursors arise from a subset of vascular endothelial cells. Interestingly, this
      differentiation is promoted by the intravascular fluid mechanical forces
      generated by the establishment of blood flow upon the initiation of heartbeat,
      and it is therefore connected with cardiovascular development in several critical
      aspects. In this review we present our current understanding of the relationship
      between vascular and definitive hematopoietic development through an historical
      analysis of the scientific evidence produced in this area of investigation.

PMID- 21945863
TI  - The transcription factor Cux2 marks development of an A-delta sublineage of TrkA
      sensory neurons.
AB  - The developmental process and unique molecular identity between the many
      different types of dorsal root ganglion (DRG) sensory neurons generated during
      embryogenesis provide the cellular basis for the distinct perceptual modalities
      of somatosensation. The mechanisms leading to the generation of different types
      of nociceptive sensory neurons remain only partly understood. Here, we show that
      the transcription factor Cux2 is a novel marker of sensory neuron subpopulations
      of three main sublineages as defined by the expression of neurotrophic factor
      receptors TrkA, TrkB and TrkC. In particular, it is expressed in a subpopulation
      of early TrkA(+) neurons that arise during the early, Ngn1-independent initiated
      neurogenesis in the DRG. Postnatally, Cux2 marks a specific subtype of A-delta
      nociceptors as seen by expression of TrkA and NF200 but absence of TrpV1.
      Analysis of Cux2 mutant mice shows that Cux2 is not required for specification of
      Trk(+) neuronal subpopulations. However, Cux2 mutant mice are hypersensitive to
      mechanical, but not to heat or cold stimuli, consistent with a requirement in the
      process of specification of the mechanoreceptive neuron circuit. Hence, our
      results show that Cux2 is expressed and may participate in development of a
      specific subtype of myelinated TrkA(+) nociceptors.

PMID- 21945864
TI  - Cardiotoxicity induced in mice by long term ketamine and ketamine plus alcohol
      treatment.
AB  - Increased use of ketamine as a recreational drug in rave party has raised lots of
      social concerns. Although its toxicity on the central nervous system (CNS) and
      urinary system had been reported, its potential adverse effects on the heart is
      still not addressed. Using our long term ketamine addiction model in which, 1
      month-old ICR mice were given ketamine intraperitoneally (i.p. 30 mg/kg) for
      different study periods (6 weeks, 16 weeks and 28 weeks). The electrocardiogram
      (ECG) and the level of troponin as well as the presence of lactate dehydrogenase
      were used together to determine the cardiac function of mice. ST elevations were
      observed in 30% of mice from 6 weeks onwards. Concomitant increase in troponin in
      serum and presence of lactate dehydrogenase positive cardiac cells were taken
      together to indicate cardiac damages. The potential interactive effects of
      alcohol (ethanol) and ketamine were also addressed and 0.5 ml of 10% ethanol was
      administrated additionally to the mice daily and orally for the last 4 weeks in
      the 28-week long-term ketamine treated animals. The cardiac functions of these
      mice deteriorated more severely as indicated by further rise in troponin levels.
      In addition, high number of lactate dehydrogenase positive cardiac cells and
      abnormal ECGs in both ketamine and ketamine plus alcohol treated models also gave
      coherent conclusions.

PMID- 21945865
TI  - Disruption of urinary odor preference and lordosis behavior in female mice given
      lesions of the medial amygdala.
AB  - Previous research showed that axonal inputs to both anterior and posterior
      subdivisions of the medial amygdala from the main and accessory olfactory bulbs
      of female mice, respectively, process volatile and non-volatile pheromonal
      signals from male conspecifics. In the present study we found that bilateral
      electrolytic lesions that included posterior portions, but not the anterior
      subdivision alone of the medial amygdala (Me) blocked the preference of estrous
      female mice to investigate volatile urinary odors from testes-intact vs.
      castrated males. Similar results were obtained in separate tests in which nasal
      contact with urinary stimuli was permitted. In addition, total time investigating
      volatile urinary stimuli was reduced in subjects with posterior Me lesions.
      Subjects were able to discriminate volatile urinary odors from testes-intact vs.
      castrated male mice, suggesting that this disruption of odor preference did not
      result from the inability of females given amygdaloid lesions to discriminate
      these male urinary odors. Bilateral lesions of the Me that were either restricted
      to the anterior or posterior subdivisions, or included areas of both regions,
      caused significant reductions in the display of lordosis behavior in estrous
      female mice. Our results suggest that the Me is a critical segment of the
      olfactory circuit that controls both mate recognition and mating behavior in the
      female mouse.

PMID- 21945866
TI  - The emulsified lipid Fabuless (Olibra) does not decrease food intake but
      suppresses appetite when consumed with yoghurt but not alone or with solid foods:
      a food effect study.
AB  - The lipid emulsion Fabuless (Olibra) has been shown in some studies to decrease
      short/medium term energy intake (EI) and prevent weight regain. The purported
      mechanism is the ileal brake. Whether Fabuless is efficacious under a range of
      dietary conditions is unknown since studies have administered the emulsion within
      a fermented, semi-liquid dairy yoghurt, and outcomes have been inconsistent. To
      determine whether Fabuless suppresses post-ingestive satiety and short-term food
      intake under a range of dietary conditions and forms we administered the emulsion
      co-presented with 185 mL water, stirred into a semi-liquid dairy yoghurt, and co
      presented with a solid food breakfast muffin. This was a cross-over study in 18
      lean men randomised to 6 treatments: (i) lipid emulsion, LE (15 g Fabuless,
      containing 4.2g lipid, 0.2 MJ)+water, (ii) lipid control, LC (15 g non-emulsified
      lipid/water, containing 4.2g lipid, 0.2 MJ)+water, (iii) lipid emulsion+yoghurt,
      LE+Y (1.2 MJ), (iv) lipid control+yoghurt, LC+Y (1.2 MJ), (v) lipid
      emulsion+muffin, LE+M (1.2 MJ), (vi) lipid control+muffin, LC+M (1.2 MJ), each
      given as a test breakfast at 8.30 am. Participants rated postprandial appetite
      sensations using visual analogue scales (VAS), and ad libitum energy intake was
      measured at a lunch meal 3.5h later. The lipid emulsion increased fullness
      compared with an energy-matched lipid control but only when administered within
      the semi-liquid fermented yoghurt (P<0.05). There were no effects on satiety
      ratings when co-presented with water or with the solid food muffin. Energy and
      macronutrient intake were not significantly decreased by any of the emulsion
      treatments. We conclude that effects are small, the format in which lipid
      emulsions are consumed influences postprandial satiety, and there is no evidence
      that this emulsion alters eating behaviour at the subsequent meal.

PMID- 21945868
TI  - Consenting practice for laparoscopic cholecystectomy - are we doing enough to
      warn patients about their operation?
AB  - INTRODUCTION: Provision of informed consent prior to surgery is fundamental in
      allowing patients to make balanced choices about their care. This study compares
      consenting practice amongst different grade of surgeons for Laparoscopic
      Cholecystectomy (LC) with specific reference to the documentation of the
      complications of surgery. Timing and delivery of source of information is also
      evaluated. METHODS: Retrospective review of medical notes of all patients
      undergoing LC at London district general hospital between September 2006 to April
      2009. RESULTS: Records were successfully retrieved for 163 patients. The five
      most commonly mentioned complications were bleeding (99%), infection (95%),
      conversion to open (93%), bile duct injury (82%) and visceral injury (65%). There
      were 27 documented complications in 23 patients and in 9 of these patients (39%)
      the specific complication was not discussed during the written consent process.
      Consultant surgeons tended to focus on important operation-specific risks such as
      bile duct injury whereas junior surgeons tend to focus on a broad range of
      general complications. CONCLUSION: Consenting practice for LC remains variable
      and is resulting in failure to warn patients of significant complications. This
      can lead to potential medico-legal implications. Having a structured consent form
      detailing all significant and common risk is one way of improving the consent
      process.

PMID- 21945867
TI  - Acquired differences in brain responses among monozygotic twins discordant for
      restrained eating.
AB  - We studied whether self-reported intent to exert cognitive control over eating
      was associated with differences in brain response to food cues, independent of
      genetic background. Subjects were ten pairs of identical twins in which one twin
      was a restrained eater and the co-twin was unrestrained, as classified by the
      Herman and Polivy Restraint Scale. Before and after ingestion of a milkshake, we
      used functional magnetic resonance imaging to measure brain response to
      photographs of objects, "fattening" food, and "non-fattening" food. At baseline,
      restrained eaters had greater activation in the left amygdala and the right
      thalamus in response to fattening food cues than did their unrestrained co-twins.
      When restrained eaters drank a milkshake, activation in response to fattening
      food photographs decreased across multiple brain areas, whereas activation
      induced by non-fattening food photographs increased. As compared to their
      unrestrained co-twins, restrained eaters who drank a milkshake had greater
      decreases in activation by fattening food images in the left amygdala and
      occipital lobe, and greater increases in activation by non-fattening food images
      in the medial orbitofrontal cortex. Because of the discordant monozygotic twin
      study design, the findings provide a rigorous level of support for the hypothesis
      that adopting an intention to restrain eating alters brain response to food cues.

PMID- 21945869
TI  - [Management of hereditary ovarian cancer].
AB  - Mutations in BRCA1 and BRCA2 genes account for the majority of hereditary breast
      and ovarian cancers. Approximately 10% of cases of ovarian cancer are due to
      germline mutations in BRCA1 and BRCA2. Ovarian cancer associated with BRCA1 and
      BRCA2 mutations has a distinct histological phenotype. This type of cancer is
      predominantly of serous or endometrioid histology and is high grade. Patients
      with BRCA1 or BRCA2 mutations should be offered risk-reducing salpingo
      oophorectomy by age 40 years, or when childbearing is complete. Nowadays there
      are no differences between the treatments provided for sporadic and hereditary
      ovarian cancer, although there are indications that targeted therapy is effective
      in women with BRCA1/BRCA2-associated tumors. Retrospective studies reveal a high
      level of sensitivity to platinum agents in BRCA-associated tumors and initial
      trials show good efficacy and tolerability for polyADP-ribose polymerase
      inhibitors in mutation carriers with advanced ovarian cancers. These agents might
      also potentially be used in chemoprevention. Authors review the current
      management of hereditary ovarian cancer.

PMID- 21945870
TI  - [Pharmacokinetic analysis of high-dose methotrexate treatments in children with
      hematologic malignancies].
AB  - Monitoring the pharmacokinetic parameters of different anticancer drugs is
      necessary because they might have several side effects. AIM: Pharmacokinetic and
      toxicity evaluation of high-dose methotrexate treatments in children with acute
      lymphoblastic leukemia. PATIENTS AND METHODS: 43 children (28 boys, 15 girls,
      mean age: 7.03 years) in 147 cases were treated with 5 g/m2/24h MTX according to
      ALL-BFM 1995 and 2002 protocols. Methotrexate and 7-hydroxi-methotrexate levels
      were measured with high pressure liquid chromatography at 24, 36, 48 hours.
      Authors registered the development of hepatotoxicity, nephrotoxicity, grade
      III/IV oral mucositis. RESULTS: Therapeutic methotrexate serum concentrations (30
      100umol/l) were achieved in 72.5% of the cases. Repeated treatments resulted
      similar serum levels. Hepatotoxicity and hypoproteinemia occurred in 17% and in
      48.9% of the cases. There was significant correlation between serum 7-hydroxi
      methotrexate and creatinine levels (p<0.05). CONCLUSION: 5 g/m2 methotrexate
      resulted reliable therapeutic serum levels with mild and reversible toxicity. 7
      hydroxi-methotexate measurements might be more useful than methotrexate levels to
      detect toxicity.

PMID- 21945871
TI  - [Surgical repair of postintubation esophago-tracheal fistulas: report of two
      cases surgically repaired].
AB  - Persistence of postintubation esophago-tracheal fistulas is a difficult
      therapeutic problem. Authors present and discuss two successfully operated cases.
      Surgical reconstruction was done via left lateral cervical approach, including
      dissection of the fistulous tract, closure of the defect on both sides by suture,
      exclusion of the esophagus with a linear stapler beyond a loop esophagostomy,
      separation the suture lines with interposing of omohioid muscle flap, and making
      a Pezzer-catheter splinted esophagostomy. In the first case the spontaneous
      recanalization of the occluded esophagus was prolonged and the fistula recurred.
      Reoperation was done by the same procedure without exclusion of the esophagus.
      The second patient needed intervention because of the prolonged closure of
      esophagostomy. Recovery of both patients was successful. In conclusion, it can be
      stated that adaptation of surgical techniques for the individual pathologic
      situation helped the authors to find the way to the successful outcome.

PMID- 21945872
TI  - [Bright's disease is mentioned in an official Hungarian medical document in the
      19th century].
AB  - The World Kidney Day was announced for the fifth time in 2011, that calls
      attention to chronic renal failure as it attains the title of endemic. Richard
      Bright (1789-1858), a British doctor was the first to recognize and describe the
      uremic state and the kidney diseases leading to it. There are many aspects that
      the readers should remember him about especially in connection with the World
      Kidney Day. During his European study tour's stage in Hungary, he was not so much
      interested in the country's medical and health conditions, rather in its economic
      and cultural life, natural history and geography. He travelled to Hungary on two
      occasions and recorded his experiences in a personal travel documentation
      illustrated with his own drawings. He finally established himself in London in
      1820 and together with Thomas Addison and Thomas Hodgkin they formed the Guy's
      Hospital's world-famous "scientist trio". Bright described the nephritis's
      classical image, nowadays known as Bright's disease for the first time at the age
      of 38 years in 1827. A presently turned up Hungarian medical certificate from
      1870 contains the Bright's disease described by Richard Bright as a written
      diagnosis. This 140-year-old document also confirms that we can be proud of our
      predecessors concerning our knowledge of kidney diseases and their application in
      daily use in Hungary, because in the past they were the ones who used the most
      advanced knowledge in their practices. One of today's greatest challenges for us
      is to be able to inform healthy and ill people alike properly about kidney
      diseases and their prevention or management. Place this in order to stem the
      epidemic of chronic renal failure and still pay homage to this disease's greatest
      scientist, Richard Bright.

PMID- 21945873
TI  - [The role of the publication "School and Health" (1933-1939) in medical history].

PMID- 21945875
TI  - Analysis of DNA mismatch repair proteins expression and BRAF V600E mutation in a
      subset of early- and late-onset colorectal carcinoma patients in Mexico.
AB  - BACKGROUND AND AIMS: A third of colorectal carcinomas (CRC) affect patients <50
      years of age. Fifteen percent of CRC cases with microsatellite instability are
      due to inherited germ-line mutations in DNA mismatch repair genes. The rest have
      an epigenetic hypermethylation of the MLH1 promoter in whom the BRAF V600E
      mutation is a common hallmark. Immunohistochemistry helps to classify colorectal
      cancers with 100% specificity and 92% sensitivity. We undertook this study to
      determine if age is a risk factor for defective MMR protein expression and BRAF
      mutations in our population and to compare these results with the
      histopathological tumor features. METHODS: Immunohistochemistry for MLH1 and MSH2
      and RT-PCR BRAF V600E mutation was performed on tissue specimens from 57 patients
      <50 years of age. Data on age, gender, tumor location, histology, depth of
      infiltration, and the presence of metastatic lymph nodes were collected. Forty
      eight patients >50 years of age were used as a control group. A statistical
      analysis using ANOVA, chi(2), and Spearman's rho test were performed. RESULTS:
      Absent MMR protein expression was more prevalent in patients <50 years of age. No
      BRAF V600E mutations were detected in either group. Medullary and mucinous types
      were more prevalent among young patients, whereas intestinal type was more
      frequent in older patients (p = 0.0008). No differences were found regarding
      clinicopathological stages between groups. CONCLUSIONS: We found an association
      between young age and defective MMR expression. No V600E BRAF mutations were
      detected in either group.

PMID- 21945876
TI  - C-reactive protein is directly associated with urinary albumin-to-creatinine
      ratio.
AB  - BACKGROUND AND AIMS: There are no studies that elucidate whether the role of
      inflammation in the increase of urinary albumin is independent, mediated by
      family history or by risk factors acquired during life in the offspring of
      subjects with type 2 diabetes. We undertook this study to evaluate whether
      elevated C-reactive protein (CRP) levels are independently associated with
      urinary albumin-to-creatinine ratio (UACR) in the offspring of subjects with
      diabetic nephropathy. METHODS: A total of 64 healthy males and healthy
      nonpregnant females, offspring of subjects with diabetic nephropathy, aged 18-69
      years, and with body mass index <=35 kg/m(2) were enrolled in a cross-sectional
      study. Hypertension, glucose metabolic disorders, metabolic syndrome, smoking,
      alcohol intake, chronic or acute infections, renal disease, neoplasm,
      cardiovascular disease, degenerative disease, intake of anti-inflammatory drugs,
      exercise, or sexual intercourse in the previous 72 h were exclusion criteria.
      Subjects with high-sensitivity CRP (hsCRP) levels >=3.0 mg/dL were compared with
      a gender- and age-matched control group of subjects with hsCRP levels <3.0 mg/dL.
      RESULTS: The multivariate linear regression analysis showed that hsCRP (B = 0.50,
      beta = 0.583, p = 0.02), total body fat (B = -2.80, beta = 0.473, p = 0.03), BMI
      (B = -1.45, beta = 0.390, p = 0.04) and waist circumference (B = 0.89, beta =
      0.407, p = 0.04) are predictors for elevation of UACR (Table 2). However, in the
      stepwise model only hsCRP (B = 0.674; beta = 0.314; p = 0.04) remained
      significantly associated with UACR. CONCLUSIONS: Our results show that
      independent of the primary risk factors, elevated hsCRP levels are associated
      with UACR.

PMID- 21945877
TI  - Association of mtDNA haplogroup F with healthy longevity in the female Chuang
      population, China.
AB  - Human longevity is a complex heritable genetic trait. Based on substantial
      evidence from model organisms, it is clear that mitochondria play a pivotal role
      in aging and lifespan. However, the effects that mitochondrial genome variations
      have upon longevity and longevity-related phenotypes in Chuang people in China
      have yet to be established. By genotyping 15 variants for 10 haplogroups in 738
      Chuang subjects, including 367 long-lived individuals and 371 controls, we found
      that haplogroup F was significantly associated with longevity in females of
      Zhuang population of China (p=0.003, OR: 2.01, 95%CI: 1.263-3.197). Additionally,
      haplogroup F was related to higher HDL levels (p<0.05) in long-lived individuals.
      Further analysis suggests that the non-synonymous variant m.13928G>C in
      haplogroup F was also associated with longevity in female Zhuang Chinese which
      might account for the beneficial effect of F.

PMID- 21945879
TI  - Synergy in biofilm formation between Fusobacterium nucleatum and Prevotella
      species.
AB  - The formation of biofilm by anaerobic, Gram-negative bacteria in the subgingival
      crevice plays an important role in the development of chronic periodontitis. The
      aim of this study was to characterize the role of coaggregation between
      Fusobacterium nucleatum and Prevotella species in biofilm formation.
      Coaggregation between F. nucleatum and Prevotella species was determined by
      visual assay. Effect of co-culture of the species on biofilm formation was
      assessed by crystal violet staining. Effect of soluble factor on biofilm
      formation was also examined using culture supernatant and two-compartment co
      culture separated by a porous membrane. Production of autoinducer-2 (AI-2) by the
      organisms was evaluated using Vibrio harveyi BB170. Cells of all F. nucleatum
      strains coaggregated with Prevotella intermedia or Prevotella nigrescens with a
      score of 1-4. Addition of ethylenediamine tetraacetic acid or l-lysine inhibited
      coaggregation. Coaggregation disappeared after heating of P. intermedia or P.
      nigrescens cells, or Proteinase K treatment of P. nigrescens cells. Co-culture of
      F. nucleatum ATCC 25586 with P. intermedia or P. nigrescens strains increased
      biofilm formation compared with single culture (p < 0.01); co-culture with
      culture supernatant of these strains, however, did not enhance biofilm formation
      by F. nucleatum. Production of AI-2 in Prevotella species was not related to
      enhancement of biofilm formation by F. nucleatum. These findings indicate that
      physical contact by coaggregation of F. nucleatum strains with P. intermedia or
      P. nigrescens plays a key role in the formation of biofilm by these strains.

PMID- 21945880
TI  - Lethal human neutropenic entercolitis caused by Clostridium chauvoei in the
      United States: tip of the iceberg?
AB  - The patient is a 44-year-old woman with metastatic grade 3 intra-ductal carcinoma
      of the breast who was started on palliative chemotherapy (docetaxel) 10 days
      prior to admission and presented to the emergency center complaining of diffuse
      abdominal pain and generalized weakness. CT abdomen showed diffuse bowel wall
      thickening from the cecum to the transverse colon with free fluid in the pelvis.
      The patient was neutropenic on admission (absolute neutrophil count of 600
      cells/MUl). She received antibiotics for 21 days for neutropenic enterocolitis.
      Blood culture isolate from admission was sent for 16s rRNA gene sequencing, which
      identified Clostridium chauvoei. While C. chauvoei has a long history of
      veterinary importance, this is the first documented case of infection caused by
      C. chauvoei in a human in the United States. C. chauvoei has a close phylogenetic
      relationship with C. septicum making the two species difficult to differentiate
      using conventional microbiologic methods. With increased use of more reliable
      detection methods the actual prevalence of C. chauvoei causing human disease may
      be higher than currently recognized.

PMID- 21945881
TI  - Introduction to the special issue of Neurobiology of Learning and Memory on
      memory impairment and disease.

PMID- 21945882
TI  - Molecular genetic and biochemical approaches for defining lipid-dependent
      membrane protein folding.
AB  - We provide an overview of lipid-dependent polytopic membrane protein folding and
      topogenesis. Lipid dependence of this process was determined by employing
      Escherichia coli cells in which specific lipids can be eliminated, substituted,
      tightly titrated or controlled temporally during membrane protein synthesis and
      assembly. The secondary transport protein lactose permease (LacY) was used to
      establish general principles underlying the molecular basis of lipid-dependent
      effects on protein domain folding, protein transmembrane domain (TM) orientation,
      and function. These principles were then extended to several other secondary
      transport proteins of E. coli. The methods used to follow proper conformational
      organization of protein domains and the topological organization of protein TMs
      in whole cells and membranes are described. The proper folding of an
      extramembrane domain of LacY that is crucial for energy dependent uphill
      transport function depends on specific lipids acting as non-protein molecular
      chaperones. Correct TM topogenesis is dependent on charge interactions between
      the cytoplasmic surface of membrane proteins and a proper balance of the membrane
      surface net charge defined by the lipid head groups. Short-range interactions
      between the nascent protein chain and the translocon are necessary but not
      sufficient for establishment of final topology. After release from the translocon
      short-range interactions between lipid head groups and the nascent protein chain,
      partitioning of protein hydrophobic domains into the membrane bilayer, and long
      range interactions within the protein thermodynamically drive final membrane
      protein organization. Given the diversity of membrane lipid compositions
      throughout nature, it is tempting to speculate that during the course of
      evolution the physical and chemical properties of proteins and lipids have co
      evolved in the context of the lipid environment of membrane systems in which both
      are mutually dependent on each other for functional organization of proteins.
      This article is part of a Special Issue entitled: Protein Folding in Membranes.

PMID- 21945883
TI  - Folding of diphtheria toxin T-domain in the presence of amphipols and fluorinated
      surfactants: Toward thermodynamic measurements of membrane protein folding.
AB  - Solubilizing membrane proteins for functional, structural and thermodynamic
      studies is usually achieved with the help of detergents, which, however, tend to
      destabilize them. Several classes of non-detergent surfactants have been designed
      as milder substitutes for detergents, most prominently amphipathic polymers
      called 'amphipols' and fluorinated surfactants. Here we test the potential
      usefulness of these compounds for thermodynamic studies by examining their effect
      on conformational transitions of the diphtheria toxin T-domain. The advantage of
      the T-domain as a model system is that it exists as a soluble globular protein at
      neutral pH yet is converted into a membrane-competent form by acidification and
      inserts into the lipid bilayer as part of its physiological action. We have
      examined the effects of various surfactants on two conformational transitions of
      the T-domain, thermal unfolding and pH-induced transition to a membrane-competent
      form. All tested detergent and non-detergent surfactants lowered the
      cooperativity of the thermal unfolding of the T-domain. The dependence of
      enthalpy of unfolding on surfactant concentration was found to be least for
      fluorinated surfactants, thus making them useful candidates for thermodynamic
      studies. Circular dichroism measurements demonstrate that non-ionic homopolymeric
      amphipols (NAhPols), unlike any other surfactants, can actively cause a
      conformational change of the T-domain. NAhPol-induced structural rearrangements
      are different from those observed during thermal denaturation and are suggested
      to be related to the formation of the membrane-competent form of the T-domain.
      Measurements of leakage of vesicle content indicate that interaction with NAhPols
      not only does not prevent the T-domain from inserting into the bilayer, but it
      can make bilayer permeabilization even more efficient, whereas the pH-dependence
      of membrane permeabilization becomes more cooperative. This article is part of a
      Special Issue entitled: Protein Folding in Membranes.

PMID- 21945884
TI  - Folding and misfolding of alpha-synuclein on membranes.
AB  - The protein alpha-synuclein is considered to play a major role in the etiology of
      Parkinson's disease. Because it is found in a classic amyloid fibril form within
      the characteristic intra-neuronal Lewy body deposits of the disease, aggregation
      of the protein is thought to be of critical importance, but the context in which
      the protein undergoes aggregation within cells remains unknown. The normal
      function of synucleins is poorly understood, but appears to involve membrane
      interactions, and in particular reversible binding to synaptic vesicle membranes.
      Structural studies of different states of alpha-synuclein, in the absence and
      presence of membranes or membrane mimetics, have led to models of how membrane
      bound forms of the protein may contribute both to functional properties of the
      protein, as well as to membrane-induced self-assembly and aggregation. This
      article reviews this area, with a focus on a particular model that has emerged in
      the past few years. This article is part of a Special Issue entitled: Protein
      Folding in Membranes.

PMID- 21945885
TI  - What are the determinants of gene expression levels and breadths in the human
      genome?
AB  - In complex organisms, different tissues express different genes, which ultimately
      shape the function and phenotype of each tissue. An important goal of modern
      biology is to understand how some genes are turned on and off in specific tissues
      and how the numbers of different gene expression products are determined. These
      aspects are named 'expression breadth' (or 'tissue specificity') and 'expression
      level', respectively. Here, we show that we can predict substantial amount of
      variation in levels and breadths of gene expression using genomic information of
      each gene. Interestingly, many genomic traits are correlated with both aspects of
      gene expression in similar directions, suggesting shared molecular pathways.
      However, to elucidate distinctive molecular mechanisms governing gene expression
      levels and breadths, we need to identify the relative significance of each
      genomic trait on these two aspects of gene expression. To this end, we developed
      a novel multivariate multiple regression method. Using this new method, we show
      that gene compactness (in particular, the mean size of exons), codon usage bias
      and non-synonymous rates have a stronger influence on expression levels compared
      with their effects on expression breadths. In contrast, the propensity of
      promoter DNA methylation is a stronger indicator of expression breadths than of
      expression levels. Interestingly, intron DNA methylation exhibits an opposite
      pattern to the promoter DNA methylation in the human genome, suggesting that DNA
      methylation may play multiple roles depending upon its genomic targets.
      Furthermore, synonymous rates have stronger associations with expression breadths
      than with expression levels in the human genome. These findings provide clues
      toward distinctive molecular mechanisms regulating different aspects of gene
      expression.

PMID- 21945886
TI  - Isoleucyl-tRNA synthetase levels modulate the penetrance of a homoplasmic
      m.4277T>C mitochondrial tRNA(Ile) mutation causing hypertrophic cardiomyopathy.
AB  - The genetic and epigenetic factors underlying the variable penetrance of
      homoplasmic mitochondrial DNA mutations are poorly understood. We investigated a
      16-year-old patient with hypertrophic cardiomyopathy harboring a homoplasmic
      m.4277T>C mutation in the mt-tRNA(Ile) (MTTI) gene. Skeletal muscle showed
      multiple respiratory chain enzyme abnormalities and a decreased steady-state
      level of the mutated mt-tRNA(Ile). Transmitochondrial cybrids grown on galactose
      medium demonstrated a functional effect of this mutation on cell viability,
      confirming pathogenicity. These findings were reproduced in transmitochondrial
      cybrids, harboring a previously described homoplasmic m.4300A>G MTTI mutation.
      The pathogenic role of the m.4277T>C mutation may be ascribed to misfolding of
      the mt-tRNA molecule, as demonstrated by the altered electrophoretic migration of
      the mutated mt-tRNA. Indeed, structure and sequence analyses suggest that
      thymidine at position 4277 of mt-tRNA(Ile) is involved in a conserved tertiary
      interaction with thymidine at position 4306. Interestingly, the mutation showed
      variable penetrance within family members, with skeletal muscle from the
      patient's clinically unaffected mother demonstrating normal muscle respiratory
      chain activities and steady-state levels of mt-tRNA(Ile), while homoplasmic for
      the m.4277T>C mutation. Analysis of mitochondrial isoleucyl-tRNA synthetase
      revealed significantly higher expression levels in skeletal muscle and
      fibroblasts of the unaffected mother when compared with the proband, while the
      transient over-expression of the IARS2 gene in patient transmitochondrial cybrids
      improved cell viability. This is the first observation that constitutively high
      levels of aminoacyl-tRNA synthetases (aaRSs) in human tissues prevent the
      phenotypic expression of a homoplasmic mt-tRNA point mutation. These findings
      extend previous observations on aaRSs therapeutic effects in yeast and human.

PMID- 21945887
TI  - Recombination and the evolution of coordinated phenotypic expression in a
      frequency-dependent game.
AB  - A long standing question in evolutionary biology concerns the maintenance of
      adaptive combinations of traits in the presence of recombination. This problem
      may be solved if positive epistasis selects for reducing the rate of
      recombination between such traits, but this requires sufficiently strong
      epistasis. Here we use a model that we developed previously to analyze a
      frequency-dependent strategy game in asexual populations, to study how adaptive
      combinations of traits may be maintained in the presence of recombination when
      epistasis is too weak to select for genetic linkage. Previously, in the asexual
      case, our model demonstrated the evolution of adaptive associations between
      social foraging strategies and learning rules. We verify that these adaptive
      associations, which are represented by different two-locus haplotypes, can easily
      be broken by genetic recombination. We also confirm that a modifier allele that
      reduces the rate of recombination fails to evolve (due to weak epistasis).
      However, we find that under the same conditions of weak epistasis, there is an
      alternative mechanism that allows an association between traits to evolve. This
      is based on a genetic switch that responds to the presence of one social foraging
      allele by activating one of the two alternative learning alleles that are carried
      by all individuals. We suggest that such coordinated phenotypic expression by
      genetic switches offers a general and robust mechanism for the evolution of
      adaptive combinations of traits in the presence of recombination.

PMID- 21945890
TI  - A frustrated three-dimensional antiferromagnet: stacked J1-J2 layers.
AB  - We study a frustrated 3D antiferromagnet of stacked J(1)-J(2) layers. The
      intermediate 'quantum spin liquid' phase, present in the 2D case, narrows with
      increasing interlayer coupling and vanishes at a triple point. Beyond this, there
      is a direct first-order transition from Neel to columnar order. Possible
      applications to real materials are discussed.

PMID- 21945889
TI  - Perceived facilitators, barriers, and changes in a randomized exercise trial for
      obese youth: a qualitative inquiry.
AB  - BACKGROUND: Purpose was to examine experiences of obese youth aged 14 to 18 years
      during their participation in the Healthy Eating, Aerobic, and Resistance
      Exercise in Youth (HEARTY) randomized controlled exercise trial. METHODS: A
      longitudinal qualitative approach was used to investigate youths' experiences
      across time points in the trial: 3-weeks (run-in phase; n = 44, 52% males), 3
      months (midpoint; n = 25), and 6-months (end of intervention; n = 24).
      Participants completed telephone interviews on perceived exercise facilitators,
      barriers, outcomes, and program preferences. Responses were subject to content
      analyses and are reported as frequencies. RESULTS: Participants joined the trial
      initially to lose weight, but focused more on fitness over time. Exercise
      behavior was influenced by a sense of achieving results, and by family and peers
      (ie, supportive comments, transportation). At 6-months, the most commonly
      perceived changes were improved fitness (50%) and appearance (46%). Suggested
      changes to the HEARTY trial included initial guidance by a trainer, and more
      varied and group-based activity. CONCLUSIONS: Exercise facilitators, barriers and
      perceived changes in an exercise trial are reported. Access to a gym, initial
      direction by a trainer, variety, and group-based activities were reported as
      desired components of an exercise intervention. Findings also point to the
      importance of involving family and peer supports.

PMID- 21945888
TI  - Visual acuity's association with levels of leisure-time physical activity in
      community-dwelling older adults.
AB  - Little is known about the effect of reduced vision on physical activity in older
      adults. This study evaluates the association of visual acuity level, self
      reported vision, and ocular disease conditions with leisure-time physical
      activity and calculated caloric expenditure. A cross-sectional study of 911
      subjects 65 yr and older from the University of Alabama at Birmingham Study of
      Aging (SOA) cohort was conducted evaluating the association of vision-related
      variables to weekly kilocalorie expenditure calculated from the 17-item Leisure
      Time Physical Activity Questionnaire. Ordinal logistic regression was used to
      evaluate possible associations while controlling for potential confounders. In
      multivariate analyses, each lower step in visual acuity below 20/50 was
      significantly associated with reduced odds of having a higher level of physical
      activity, OR 0.81, 95% CI 0.67, 0.97. Reduced visual acuity appears to be
      independently associated with lower levels of physical activity among community
      dwelling adults.

PMID- 21945891
TI  - Olfactory hallucinations in primary headache disorders: case series and
      literature review.
AB  - BACKGROUND: Olfactory hallucinations (phantosmias) have rarely been reported in
      migraine patients. Unlike visual, sensory, language, brainstem, and motor
      symptoms, they are not recognized as a form of aura by the International
      Classification of Headache Disorders. METHODS: We examined the clinical features
      of 39 patients (14 new cases and 25 from the literature) with olfactory
      hallucinations in conjunction with their primary headache disorders. RESULTS: In
      a 30-month period, the prevalence of phantosmias among all patients seen at our
      headache center was 0.66%. Phantosmias occurred most commonly in women with
      migraine, although they were also seen in several patients with other primary
      headache diagnoses. The typical hallucination lasted 5-60 minutes, occurred
      shortly before or simultaneous with the onset of head pain, and was of a highly
      specific and unpleasant odor, most commonly a burning smell. In the majority of
      patients, phantosmias diminished or disappeared with initiation of prophylactic
      therapy for headaches. CONCLUSIONS: We propose that olfactory hallucinations are
      probably an uncommon but distinctive form of migraine aura, based on their
      semiology, timing and response to headache prophylaxis.

PMID- 21945892
TI  - The influence of downward gaze and accommodation on ocular aberrations over time.
AB  - A Shack-Hartmann wavefront sensor was modified to allow measurement of ocular
      aberrations in downward gaze with binocular fixation. Subjects first performed a
      control task prior to four different trials involving a distance task or a near
      task (accommodative demand of 2.5 D) performed in primary and downward gaze (25
      degrees ). Immediately after beginning and then again 5 and 10 min after the
      commencement of each trial, ocular aberrations were measured. To observe the
      recovery in ocular aberrations following each test condition, subjects again
      viewed a distance target in primary gaze and aberration measurements were taken
      at 0, 5, and 10 min. During the distance task, small but significant changes in
      refractive power and higher order aberrations were observed in downward gaze
      compared to primary gaze. The changes in ocular aberrations that occurred in
      downward gaze recovered almost immediately after shifting gaze from downward back
      to primary gaze. During the accommodation tasks, there was a significant
      influence of gaze for changes in primary spherical aberration C(4, 0) [p=0.004]
      and secondary spherical aberration C(6, 0) [p=0.02]. There was also a significant
      gaze by time interaction (p=0.04) for changes in C(6, 0). These findings show
      that ocular aberrations change from primary to downward gaze, particularly during
      accommodation.

PMID- 21945893
TI  - Irinotecan as the key chemotherapeutic agent in second-line treatment of
      metastatic gastric cancer after failure of first-line S-1 or S-1/CDDP therapy.
AB  - BACKGROUND: S-1, an oral fluoropyrimidine, is one of the standard
      chemotherapeutic agents for the treatment of metastatic gastric cancer(MGC).
      However, the most effective second-line regimen after failure of treatment with
      first-line agents such as S-1 is yet to be determined. The aim of this study was
      to investigate the various second-line chemotherapy regimens in MGC patients.
      METHODS: We retrospectively studied patients with MGC who received second-line
      treatment after failure of the first-line S-1 or S-1/cisplatin treatment. The
      overall survival times with each second-line regimen were determined using the
      Kaplan-Meier method, and the effect on overall survival was analyzed using Cox
      regression analysis. RESULTS: The median survival time for all patients was 14. 2
      months(95% confidence interval(CI): 12. 88-15. 43 months)with a 1-year survival
      rate of 60. 4%. Kaplan-Meier analysis revealed that the second-line regimens
      containing irinotecan significantly improved the median survival time as compared
      to regimens without irinotecan(median survival time: 16. 5 and 13. 8 months,
      respectively). Cox regression analysis showed that irinotecan-containing regimens
      were associated with improved overall survival(hazard ratio: 0. 165; 95% CI: 0.
      041-0. 665). CONCLUSION: The use of irinotecan-containing regimens as second-line
      chemotherapy after failure of first-line S-1 therapy may be beneficial for MGC
      patients.

PMID- 21945895
TI  - Profiling of urinary steroids by gas chromatography-mass spectrometry detection
      and confirmation of androstenedione administration using isotope ratio mass
      spectrometry.
AB  - Androstenedione (4-androstene-3,17-dione) is banned by the World Anti-Doping
      Agency (WADA) as an endogenous steroid. The official method to confirm
      androstenedione abuse is isotope ratio mass spectrometry (IRMS). According to the
      guidance published by WADA, atypical steroid profiles are required to trigger
      IRMS analysis. However, in some situations, steroid profile parameters are not
      effective enough to suspect the misuse of endogenous steroids. The aim of this
      study was to investigate the atypical steroid profile induced by androstenedione
      administration and the detection of androstenedione doping using IRMS. Ingestion
      of androstenedione resulted in changes in urinary steroid profile, including
      increased concentrations of androsterone (An), etiocholanolone (Etio), 5alpha
      androstane-3alpha,17beta-diol (5alpha-diol), and 5beta-androstane-3alpha,17beta
      diol (5beta-diol) in all of the subjects. Nevertheless, the
      testosterone/epitestosterone (T/E) ratio was elevated only in some of the
      subjects. The rapid increases in the concentrations of An and Etio, as well as in
      T/E ratio for some subjects could provide indicators for initiating IRMS analysis
      only for a short time period, 2-22h post-administration. However, IRMS could
      provide positive determinations for up to 55h post-administration. This study
      demonstrated that, 5beta-diol concentration or Etio/An ratio could be utilized as
      useful indicators for initiating IRMS analysis during 2-36h post-administration.
      Lastly, Etio, with slower clearance, could be more effectively used than An for
      the confirmation of androstenedione doping using IRMS.

PMID- 21945896
TI  - Factorial analysis of adaptable properties of self-assembling peptide matrix on
      cellular proliferation and neuronal differentiation of pluripotent embryonic
      carcinoma.
AB  - An integrative and quantitative approach for systematically studying the effects
      of changing the matrix environment on pluripotent cell viability and neuronal
      differentiation was demonstrated. This approach, based on factorial analysis and
      a self-assembling peptide (SAP) matrix, was exemplified using P19 as a
      pluripotent cell model. In a two-level, three-factor factorial design of
      experiments, three niche factors, namely, culture dimensionality, fixed
      biochemical signal and mechanical stiffness, were simultaneously investigated. We
      found that cell growth was slowed in matrices containing IKVAV epitopes on the
      SAP constructs, and neuronal differentiation was promoted synergistically by
      culturing in a three-dimensional matrix and in the presence of IKVAV. Variation
      of the storage modulus from around 262 Pa to 672 Pa had no significant effect on
      either viability or differentiation. This approach should be applicable to
      studying how niche properties that are tunable using SAPs affect the behavior of
      pluripotent cells in general, thus generating guidelines for constructing
      artificial matrices. FROM THE CLINICAL EDITOR: In this basic science study, an
      integrative and quantitative approach to study the effects of matrix environment
      on pluripotent cell viability and neuronal differentiation is demonstrated.
      Approaches, like the one described in this paper, are applicable to studying how
      self assembling peptides affect the behavior of pluripotent cells in general.

PMID- 21945894
TI  - Regulation of endothelial cell development by ETS transcription factors.
AB  - The ETS family of transcription factors plays an essential role in controlling
      endothelial gene expression. Multiple members of the ETS family are expressed in
      the developing endothelium and evidence suggests that the proteins function, to
      some extent, redundantly. However, recent studies have demonstrated a crucial non
      redundant role for ETV2, as a primary player in specification and differentiation
      of the endothelial lineage. Here, we review the contribution of ETS factors, and
      their partner proteins, to the regulation of embryonic vascular development.

PMID- 21945897
TI  - Self-folding immunoprotective cell encapsulation devices.
AB  - Cell encapsulation therapy (CET) provides an attractive means to transplant cells
      without the need for immunosuppression. The cells are immunoisolated by
      surrounding them with a synthetic, semipermeable nanoporous membrane that allows
      selective permeation of nutrients and therapeutics while isolating the cells from
      hostile immune components. This communication describes the fabrication and in
      vitro characterization of lithographically structured and self-folded containers
      for immunoprotective cell encapsulation. Lithographic patterning ensured
      identical shapes, sizes, tunable porosity, and precise volumetric control,
      whereas self-folding enabled transformation of two-dimensional porous membranes
      into cubes, ensuring that pores were present in all three dimensions for adequate
      diffusion of O(2) and other nutrients to encapsulated cells. We fabricated
      containers with varying pore sizes and observed that pores sizes of approximately
      78 nm were sufficient to significantly inhibit diffusion of IgG (the smallest
      antibody) and permit adequate diffusion of insulin, highlighting the possibility
      to utilize these containers to develop a lithographically structured
      bioartificial pancreas. FROM THE CLINICAL EDITOR: In this paper, a novel
      immunoisolation technique is presented to enable cell transplant survival by
      surrounding them with a synthetic, semipermeable nanoporous membrane that allows
      selective permeation of nutrients and therapeutics while isolating the cells from
      hostile immune components. This method may pave the way to effective pancreatic
      islet cell transplantation.

PMID- 21945898
TI  - Nanostructure of healthy and caries-affected human teeth.
AB  - Spatially resolved small-angle x-ray scattering based on synchrotron radiation
      combines the quantitative assessment of nanometer-sized components using
      scattering with the real-space imaging by means of scanning. The method enables
      us to study the effect of caries-induced damages on the inorganic and organic
      nanoscopic components in human teeth. We demonstrate for several 200- to 500-MUm
      thin tooth slices that the bacterial processes dissolve the ceramic components in
      enamel and dentin, but the dentinal collagen network remains practically
      unaffected with respect to its abundance and orientation in early stages of
      caries and in parts of extended carious lesions. Consequently, we speculate that
      future caries treatments can be developed reversing the effect of bacterial
      attacks by means of suitable remineralization of the dentin. FROM THE CLINICAL
      EDITOR: In this groundbreaking study of caries pathology using synchrotron-based
      X-ray scattering, the authors demonstrated that while bacterial processes do
      dissolve the ceramic components in enamel and dentin; however, the dentinal
      collagen network remains unaffected, enabling the development of future caries
      treatments that re-mineralize the dentin.

PMID- 21945899
TI  - Improved antibacterial and antibiofilm activity of magnesium fluoride
      nanoparticles obtained by water-based ultrasound chemistry.
AB  - Antibiotic resistance has prompted the search for new agents that can inhibit
      bacterial growth. We recently reported on the antimicrobial and antibiofilm
      activities of nanosized magnesium fluoride (MgF(2)) nanoparticles (NPs)
      synthesized in ionic liquid using microwave chemistry. In this article, we
      describe a novel water-based synthesis of MgF(2) NPs using sonochemistry. The
      sonochemical irradiation of an aqueous solution of [Mg(OAc)(2)?(H(2)O)(4)]
      containing acidic HF as the fluorine ion source afforded crystalline well-shaped
      spherical MgF(2) NPs that showed much improved antibacterial properties against
      two common bacterial pathogens (Escherichia coli and Staphylococcus aureus). We
      were also able to demonstrate that the antimicrobial activity was dependent on
      the size of the NPs. In addition, using the described sonochemical process, we
      coated glass surfaces and demonstrated inhibition of bacterial colonization for 7
      days. Finally, the antimicrobial activity of MgF(2) NPs against established
      biofilms was also examined. Taken together our results highlight the potential to
      further develop the concept of utilizing these metal fluoride NPs as novel
      antimicrobial and antibiofilm agents. FROM THE CLINICAL EDITOR: In this article,
      the authors describe a novel aqueous synthesis of magnesium fluoride NPs using
      sonochemistry. These nanoparticles have improved antibacterial and antibiofilm
      activity compared to their counterparts with traditional synthesis methods.

PMID- 21945900
TI  - Antiangiogenic effect of silicate nanoparticle on retinal neovascularization
      induced by vascular endothelial growth factor.
AB  - Angiogenesis-related blindness indicates the spectrum of retinal diseases that
      are caused by pathological angiogenesis, resulting in catastrophic vision loss.
      We aimed to demonstrate the antiangiogenic effect of silicate nanoparticles
      (SiNPs) on the retinal neovascularization. No direct toxicity of SiNPs was
      observed on retinal neuronal or endothelial cells, nor on the retinal tissue.
      Furthermore, intravitreal injection of SiNPs effectively reduced anomalous
      retinal angiogenesis in oxygen-induced retinopathy mice. SiNPs also effectively
      inhibited in vitro vascular endothelial growth factor (VEGF)-induced
      angiogenesis. Via suppression of VEGF receptor-2 phosphorylation induced by VEGF,
      SiNPs blocked ERK 1/2 activation. SiNPs could be an inhibitor of the potency and
      safety of retinal neovascularization that is mediated by VEGF and utilized in the
      treatment of angiogenesis-related blindness. FROM THE CLINICAL EDITOR: In this
      important preclinical study, silicate NP-s are studied to address retinal
      neovascularization, an important pathomechanism of different retinal diseases
      that could lead to catastrophic vision loss. The authors conclude that SiNP-s
      could be utilized as inhibitors of retinal neovascularization mediated by VEGF
      and propose future applications in the treatment of angiogenesis-related
      blindness.

PMID- 21945901
TI  - Magnetic-plasmonic nanoparticles for the life sciences: calculated optical
      properties of hybrid structures.
AB  - Magnetic-plasmonic nanoparticles, combining magnetic and plasmonic components,
      are promising structures for use in life sciences. Optical properties of core
      shell magnetite-gold nanostructures, such as the wavelength of the plasmon
      resonance, the extinction cross-section, and the ratio of scattering to
      absorption at the plasmon wavelength are critical parameters in the search for
      the most suitable particles for envisioned applications. Using Mie theory and the
      discrete dipole approximation (DDA), optical spectra as a function of
      composition, size, and shape of core-shell nanospheres and nanorods were
      calculated. Calculations were done using simulated aqueous media, used throughout
      the life sciences. Our results indicate that in the advantageous near-infrared
      region (NIR), although magnetic-plasmonic nanospheres produced by available
      chemical methods lack the desirable tunability of optical characteristics,
      magnetic-plasmonic nanorods can achieve the desired optical properties at
      chemically attainable dimensions. The presented results can aid in the selection
      of suitable magnetic-plasmonic structures for applications in life sciences. FROM
      THE CLINICAL EDITOR: In this basic science study, magnetic-plasmonic
      nanoparticles are studied for future applications in life sciences. Optical
      properties of core-shell magnetite-gold nanostructures, such as the wavelength of
      the plasmon resonance, the extinction cross-section, and the ratio of scattering
      to absorption at the plasmon wavelength are critical parameters in the search for
      the most suitable particles for proposed future applications.

PMID- 21945902
TI  - Progression of tau pathology in cholinergic Basal forebrain neurons in mild
      cognitive impairment and Alzheimer's disease.
AB  - Tau is a microtubule-associated protein that forms neurofibrillary tangles (NFTs)
      in the selective vulnerable long projection neurons of the cholinergic basal
      forebrain (CBF) in Alzheimer's disease (AD). Although CBF neurodegeneration
      correlates with cognitive decline during AD progression, little is known about
      the temporal changes of tau accumulation in this region. We investigated tau
      posttranslational modifications during NFT evolution within the CBF neurons of
      the nucleus basalis (NB) using tissue from subjects with no cognitive impairment,
      mild cognitive impairment, and AD. The pS422 antibody was used as an early tau
      pathology marker that labels tau phosphorylated at Ser422; the TauC3 antibody was
      used to detect later stage tau pathology. Stereologic evaluation of NB tissue
      immunostained for pS422 and TauC3 revealed an increase in neurons expressing
      these tau epitopes during disease progression. We also investigated the
      occurrence of pretangle tau events within cholinergic NB neurons by dual staining
      for the cholinergic cell marker, p75(NTR), which displays a phenotypic down
      regulation within CBF perikarya in AD. As pS422+ neurons increased in number,
      p75(NTR)+ neurons decreased, and these changes correlated with both AD
      neuropathology and cognitive decline. Also, NFTs developed slower in the CBF
      compared with previously examined cortical regions. Taken together, these results
      suggest that changes in cognition are associated with pretangle events within NB
      cholinergic neurons before frank NFT deposition.

PMID- 21945904
TI  - Unintentional temporal context-based prediction of emotional faces: an
      electrophysiological study.
AB  - The ability to extract sequential regularities embedded in the temporal context
      or temporal structure of sensory events and to predict upcoming events based on
      the extracted sequential regularities plays a central role in human cognition. In
      the present study, we demonstrate that, without any intention, upcoming emotional
      faces can be predicted based on sequential regularities, by showing that
      prediction error responses as reflected by visual mismatch negativity (MMN), an
      event-related brain potential (ERP) component, were evoked in response to
      emotional faces that violated a regular alternation pattern of 2 emotional faces
      (fearful and happy faces) under a situation where the emotional faces themselves
      were unrelated to the participant's task. Face-inversion and negative-bias
      effects in the visual MMN further indicated the involvement of holistic face
      representations. In addition, through successive source analyses of the visual
      MMN, it was revealed that the prediction error responses were composed of
      activations mainly in the face-responsible visual extrastriate areas and the
      prefrontal areas. The present results provide primary evidence for the existence
      of the unintentional temporal context-based prediction of biologically relevant
      visual stimuli as well as empirical support for the major engagement of the
      visual and prefrontal areas in unintentional temporal context-based prediction in
      vision.

PMID- 21945905
TI  - Development and evaluation of xanthan gum-facilitated ethyl cellulose
      microsponges for controlled percutaneous delivery of diclofenac sodium.
AB  - In this study, xanthan gum-facilitated ethyl cellulose microsponges were prepared
      by the double emulsification technique and subsequently dispersed in a carbopol
      gel base for controlled delivery of diclofenac sodium to the skin. Scanning
      electron microscopy revealed the porous, spherical nature of the microsponges.
      Increase in the drug/polymer ratio (0.4:1, 0.6:1, 0.8:1, m/m) increased their
      yield (79.1-88.5%), drug entrapment efficiency (50.0-64.1%), and mean particle
      diameter (181-255 MUm). Compared to the microsponges with high drug/polymer ratio
      (0.8:1, m/m), the flux of entrapped drug through excised rat skin decreased by
      19.9% and 17.0%, respectively, for the microsponges prepared at low and
      intermediate drug/polymer ratios. When an equivalent amount of pure drug (not
      entrapped into microsponges) was dispersed into the gel base and the flux was
      compared, the microsponges (drug/polymer ratio 0.8:1, m/m) were found to reduce
      the flux by 33.3%. Whether the drug was dispersed either in un-entrapped or
      entrapped form into the gel base, the drug permeation through rat skin followed
      Higuchi's diffusion kinetic model. The microsponges prepared at the lowest
      drug/polymer ratio exhibited a comparatively slower drug permeation profile and
      were hence considered most suitable for controlled drug delivery application.
      FTIR spectroscopy and DSC analyses indicated the chemically stable, amorphous
      nature of the drug in these microsponges. The gel containing these optimized
      microsponges was comparable to that of a commercial gel formulation and did not
      show serious dermal reactions. Hence, the microsponge system obtained at the
      lowest drug/polymer ratio could be useful for controlled release of diclofenac
      sodium to the skin.

PMID- 21945903
TI  - CCR3 Blockade Attenuates Eosinophilic Ileitis and Associated Remodeling.
AB  - Intestinal remodeling and stricture formation is a complication of inflammatory
      bowel disease (IBD) that often requires surgical intervention. Although
      eosinophils are associated with mucosal remodeling in other organs and are
      increased in IBD tissues, their role in IBD-associated remodeling is unclear.
      Histological and molecular features of ileitis and remodeling were assessed using
      immunohistochemical, histomorphometric, flow cytometric, and molecular analysis
      (real-time RT-PCR) techniques in a murine model of chronic eosinophilic ileitis.
      Collagen protein was assessed by Sircol assay. Using a spontaneous eosinophilic
      Crohn's-like mouse model SAMP1/SkuSlc, we demonstrate an association between
      ileitis progression and remodeling over the course of 40 weeks. Mucosal and
      submucosal eosinophilia increased over the time course and correlated with
      increased histological inflammatory indices. Ileitis and remodeling increased
      over the 40 weeks, as did expression of fibronectin. CCR3-specific antibody
      mediated reduction of eosinophils resulted in significant decrease in goblet cell
      hyperplasia, muscularis propria hypertrophy, villus blunting, and expression of
      inflammatory and remodeling genes, including fibronectin. Cellularity of local
      mesenteric lymph nodes, including T- and B-lymphocytes, was also significantly
      reduced. Thus, eosinophils participate in intestinal remodeling, supporting
      eosinophils as a novel therapeutic target.

PMID- 21945906
TI  - Design and evaluation of a bioadhesive film for transdermal delivery of
      propranolol hydrochloride.
AB  - The objective of the study was to develop a suitable trans-dermal delivery system
      for propranolol hydrochloride (PPL) via employing chitosan as a film former. Drug
      concentration uniformity, thickness, moisture uptake capacity and skin
      bioadhesion of the films were characterized. The effects of chitosan and PPL
      concentration and different penetration enhancers on the release and permeation
      profiles from the films were investigated. Skin irritation of the candidate film
      was evaluated. Chitosan film (PPL 2 mg cm(-2), chitosan 2%, m/m, cineol 10%, m/m)
      was found nonirritant and achieved 88.2% release after 8 hours in phosphate
      buffer. Significant high (p < 0.001) permeation of PPL through rat skin was
      obtained using this film compared to the film without enhancer (about 8 times
      enhancement factor), making it a promising trans-dermal delivery system for PPL.

PMID- 21945908
TI  - Tigecycline attenuates polymorphonuclear leukocyte (PMN) receptors but not
      functions.
AB  - Tigecycline achieves high intracellular concentrations in polymorphonuclear
      leukocytes (PMNs). To evaluate the effects of tigecycline on human PMNs, PMNs
      were incubated with tigecycline dilutions (0.1 to 100 mg L-1). Phagocytosis
      associated PMN Fcgamma- and complement receptors as well as phagocytosis and
      oxidative burst induced by Staphylococcus aureus were measured by flow cytometry.
      Incubation with tigecycline caused small but significant decreases in the density
      of complement receptors CD11b and CD35 (all concentrations) and Fcgamma receptors
      CD16 and CD32 (high concentrations), but not in the percentages of receptor
      bearing cells, except for small reductions in the proportions of CD16 positive
      cells at high concentrations. Tigecycline had no effect on phagocytosis or
      oxidative burst induced by S. aureus. Tigecycline was thus associated with
      decreased density of PMN complement and (at high concentrations) Fcgamma
      receptors. Although statistically significant, the differences were small and did
      not influence the PMN function as measured by phagocytosis and oxidative burst.

PMID- 21945907
TI  - Simultaneous estimation of ramipril, acetylsalicylic acid and atorvastatin
      calcium by chemometrics assisted UV-spectrophotometric method in capsules.
AB  - In the present work, three different spectrophotometric methods for simultaneous
      estimation of ramipril, aspirin and atorvastatin calcium in raw materials and in
      formulations are described. Overlapped data was quantitatively resolved by using
      chemometric methods, viz. inverse least squares (ILS), principal component
      regression (PCR) and partial least squares (PLS). Calibrations were constructed
      using the absorption data matrix corresponding to the concentration data matrix.
      The linearity range was found to be 1-5, 10-50 and 2-10 MUg mL-1 for ramipril,
      aspirin and atorvastatin calcium, respectively. The absorbance matrix was
      obtained by measuring the zero-order absorbance in the wavelength range between
      210 and 320 nm. A training set design of the concentration data corresponding to
      the ramipril, aspirin and atorvastatin calcium mixtures was organized
      statistically to maximize the information content from the spectra and to
      minimize the error of multivariate calibrations. By applying the respective
      algorithms for PLS 1, PCR and ILS to the measured spectra of the calibration set,
      a suitable model was obtained. This model was selected on the basis of RMSECV and
      RMSEP values. The same was applied to the prediction set and capsule formulation.
      Mean recoveries of the commercial formulation set together with the figures of
      merit (calibration sensitivity, selectivity, limit of detection, limit of
      quantification and analytical sensitivity) were estimated. Validity of the
      proposed approaches was successfully assessed for analyses of drugs in the
      various prepared physical mixtures and formulations.

PMID- 21945909
TI  - Effect of formulation parameters on the drug release and floating properties of
      gastric floating two-layer tablets with acetylsalicylic acid.
AB  - Floating dosage forms of acetylsalicylic acid, used for its antithrombotic
      effect, were developed to prolong gastric residence time and increase
      bioavailability. In the two-layer tablet formulation, hydroxypropyl
      methylcellulose (HPMC) of high viscosity and an effervescent mixture of citric
      acid and sodium bicarbonate formed the floating layer. The release layer
      contained the drug, direct tableting agent and different types of matrix-forming
      polymers such as HPMC of low viscosity, sodium carboxymethylcellulose and
      chitosan. Tablets were prepared using a direct compression technique. The effect
      of formulation variables on physicochemical and floating properties and the drug
      release from tablets were investigated. Floating ability was dependent on the
      amount of effervescent agent and gel-forming polymer of the floating layer. Drug
      release was prolonged to 8 hours by changing the type and viscosity of the matrix
      forming polymer in the drug-loading layer and all formulations showed a diffusion
      release mechanisms.

PMID- 21945910
TI  - A two pulse drug delivery system for amoxicillin: an attempt to counter the
      scourge of bacterial resistance against antibiotics.
AB  - Bearing in mind the present scenario of the increasing biological tolerance of
      bacteria against antibiotics, a time controlled two pulse dosage form of
      amoxicillin was developed. The compression coating inlay tablet approach was used
      to deliver the drug in two pulses to different parts of the GIT after a well
      defined lag time between the two releases. This was made possible by formulating
      a core containing one of the two drug fractions (intended to be delivered as the
      second pulse), which was spray coated with a suspension of ethyl cellulose and a
      hydrophilic but water insoluble agent as a pore former (microcrystalline
      cellulose). Coating of up to 5% (m/m) was applied over the core tablet, giving a
      corresponding lag of 3, 5, 7 and 12 h. Increasing the level of coating led to
      retardation of the water uptake capacity of the core, leading to prolongation of
      the lag time. Microcrystalline cellulose was used as a hydrophilic but water
      insoluble porosity modifier in the barrier layer, varying the concentration of
      which had a significant effect on shortening or prolongation of the lag time.
      This coated system was further partially compression coated with the remaining
      drug fraction (to be released as the first immediate release pulse) with a
      disintegrant, giving a final tablet. The core tablet and the final two pulse
      inlay tablet were further investigated for their in vitro performance.

PMID- 21945911
TI  - Dissolution rate enhancement of gliclazide by ordered mixing.
AB  - The poorly water soluble antidiabetic drug gliclazide was selected to study the
      effect of excipients on dissolution rate enhancement. Ordered mixtures of
      micronized gliclazide with lactose, mannitol, sorbitol, maltitol and sodium
      chloride were prepared by manual shaking of glass vials containing the drug and
      excipient(s). Different water soluble excipients, addition of surfactant and
      superdisintegrant, drug concentration and carrier particle size influenced the
      dissolution rate of the drug. Dissolution rate studies of the prepared ordered
      mixtures revealed an increase in drug dissolution with all water soluble
      excipients. The order of dissolution rate improvement for gliclazide was mannitol
      > lactose > maltitol > sorbitol > sodium chloride. Composite granules of the
      particle size range 355-710 MUm were superior in increasing the drug dissolution
      rate from ordered mixtures. Reducing the carrier particle size decreased the
      dissolution rate of the drug as well as the increase in drug concentration.
      Kinetic modeling of drug release data fitted best the Hixson-Crowell model, which
      indicates that all the ordered mixture formulations followed the cube root law
      fairly well.

PMID- 21945912
TI  - Antitumor and anti-inflammatory activities of polysaccharides isolated from
      Ganoderma lucidum.
AB  - In this study, polysaccharides were isolated from Ganoderma lucidum
      (Polyporaceae) and their antitumor and anti-inflammatory activities were
      investigated using in vivo models. Potential antitumor activity was shown by G.
      lucidum polysaccharides (GLP) against solid tumor induced by Ehrlich's ascites
      carcinoma cells. GLP at 100 mg kg(-1) body mass showed 80.8 and 77.6% reduction
      in tumour volume and tumour mass, respectively, when administered 24 h after
      tumour implantation. Again, GLP at the same dose but when administered prior to
      tumour inoculation, showed 79.5 and 81.2% inhibition of tumour volume and tumour
      mass, respectively. GLP showed significant dose-dependent activity in
      carrageenean-induced (acute) and formalin-induced (chronic) inflammation assays.
      At 100 mg kg(-1), GLP exhibited 57.6 and 58.2% inhibition in carrageenean-induced
      and formalin-induced assays, respectively.

PMID- 21945913
TI  - Tailoring of drug delivery of 5-fluorouracil to the colon via a mixed film coated
      unit system.
AB  - The study was carried out to establish the effectiveness of a mixed film composed
      of ethylcellulose/Eudragit S100 for colonic delivery of 5-flourouracil (5-FU).
      Tablets cores containing 5-FU were prepared by direct compression method by
      coating at different levels (2-9%, m/m) with a non-aqueous solution containing
      ethylcellulose/Eudragit S100. Coated tablets were studied for the in vitro
      release of 5-FU and the samples were analyzed spectrophotometrically at 266 nm.
      Drug release from coated systems depended on the thickness of the mixed film and
      the composition of the core. Channel formation was initiated in the coat by
      dissolution of the Eudragit S100 fraction at higher pH in the colonic region. The
      release was found to be higher in tablets containing Avicel as filler owing to
      its wicking action compared to that from lactose containing cores. Furthermore,
      batches containing superdisintegrant (1%, m/m Cross-PVP) along with Avicel in the
      core released approximately 81.1% drug during the colonic transit time. Kinetic
      studies indicated that all the formulations followed first-order release
      kinetics. The developed delivery system will expectedly deliver the drug to the
      colon.

PMID- 21945914
TI  - Synthesis and biological evaluation of some novel 2-phenyl benzimidazole-1
      acetamide derivatives as potential anthelmintic agents.
AB  - The present study describes synthesis of a series of 2-phenyl benzimidazole-1
      acetamide derivatives and their evaluation for anthelmintic activity using Indian
      adult earthworms, Pheretima posthuma. The structure of the title compounds was
      elucidated by elemental analysis and spectral data. The compounds 4-({[2-(4
      nitrophenyl)-1H-benzimidazol-1-yl]acetyl}amino) benzoic acid (3a), N-ethyl-2-[2
      (4-nitrophenyl)-1H-benzimidazol-1-yl] acetamide (3c), N-benzyl-2-[2-(4
      nitrophenyl)-1H-benzimidazol-1-yl] acetamide (3d), N-(4-hydroxyphenyl)-2-[2-(4
      nitrophenyl)-1H-benzimidazol-1-yl] acetamide (3f), 2-[2-(4-nitrophenyl)-1H
      benzimidazol-1-yl]-N-phenyl acetamide (3h), 2-[2-(4-chlorophenyl)-1H-benzimidazol
      1-yl]-N'-phenylacetohydrazide (3k), 2-[2-(4-chlorophenyl)-1H-benzimidazol-1-yl]-N
      (4-nitrophenyl) acetamide (3n) and 2-[2-(4-chlorophenyl)-1H-benzimidazol-1-yl]-N
      phenyl acetamide (3q) were found better to paralyze worms whereas N-ethyl-2-[2-(4
      nitrophenyl)-1H-benzimidazol-1-yl] acetamide (3c), N-(4-nitrophenyl)-2-[2-(4
      nitrophenyl)-1H-benzimidazol-1-yl] acetamide (3e), 4-({[2-(4-chlorophenyl)-1H
      benzimidazol-1-yl] acetyl}amino) benzoic acid (3j), 2-[2-(4-chlorophenyl)-1H
      benzimidazol-1-yl]-N-ethyl acetamide (31) and 2-[2-(4-chlorophenyl)-1H
      benzimidazol-1-yl]-N-phenyl acetamide (3q) were better to cause death of worms
      compared to the anthelmintic drug albendazole.

PMID- 21945915
TI  - Ghrelin potentiates TSH-induced expression of the thyroid tissue-specific genes
      thyroglobulin, thyroperoxidase and sodium-iodine symporter, in rat PC-Cl3 Cells.
AB  - Ghrelin is a 28-amino-acid peptide that stimulates pituitary growth-hormone
      secretion and modulates food-intake and energy metabolism in mammals. It is
      mainly secreted by the stomach, but it is also expressed in many other tissues
      such as cartilage or the thyroid gland. In the present study we have analyzed by
      RT-PCR and using immunohistochemistry and immunofluorescence the expression and
      tissue distribution of ghrelin and its functional receptor (GHS-R type 1alpha) in
      thyroid cell-lines and in normal and pathological rat thyroid tissue.
      Additionally, by measuring the incorporation of BrdU, we have investigated if, as
      previously noted for FRTL-5 cells, ghrelin enhances the proliferation rate in the
      PC-Cl3 rat-thyrocyte cell-line. Finally, we have determined the stimulatory
      effect of ghrelin on TSH-induced expression of the tissue-specific key genes
      involved in the synthesis of thyroid hormone: thyroglobulin, thyroperoxidase and
      sodium-iodine symporter. Our data provide direct evidence that C-cell secreted
      ghrelin may be involved in the paracrine regulation of the thyroid follicular
      cell function.

PMID- 21945916
TI  - A new look at the renin-angiotensin system--focusing on the vascular system.
AB  - The renin-angiotensin system (RAS), critically involved in the control of blood
      pressure and volume homeostasis, is a dual system comprising a circulating
      component and a local tissue component. The rate limiting enzyme is renin, which
      in the circulating RAS derives from the kidney to generate Ang II, which in turn
      regulates cardiovascular function by binding to AT(1) and AT(2) receptors on
      cardiac, renal and vascular cells. The tissue RAS can operate independently of
      the circulating RAS and may be activated even when the circulating RAS is
      suppressed or normal. A functional tissue RAS has been identified in brain,
      kidney, heart, adipose tissue, hematopoietic tissue, gastrointestinal tract,
      liver, endocrine system and blood vessels. Whereas angiotensinsinogen,
      angiotensin converting enzyme (ACE), Ang I and Ang II are synthesized within
      these tissues, there is still controversy as to whether renin is produced locally
      or whether it is taken up from the circulation, possibly by the (pro)renin
      receptor. This is particularly true in the vascular wall, where expression of
      renin is very low. The exact function of the vascular RAS remains elusive, but
      may contribute to fine-tuning of vascular tone and arterial structure and may
      amplify vascular effects of the circulating RAS, particularly in pathological
      conditions, such as in hypertension, atherosclerosis and diabetes. New concepts
      relating to the vascular RAS have recently been elucidated including: (1) the
      presence of functionally active Ang-(1-7)-Mas axis in the vascular system, (2)
      the importance of the RAS in perivascular adipose tissue and cross talk with
      vessels, and (3) the contribution to vascular RAS of Ang II derived from immune
      and inflammatory cells within the vascular wall. The present review highlights
      recent progress in the RAS field, focusing on the tissue system and particularly
      on the vascular RAS.

PMID- 21945917
TI  - New ESC/EAS Guidelines for the management of dyslipidaemias - any controversies
      behind the consensus?

PMID- 21945918
TI  - 'I'm just short for my weight, doctor': body weight and risk.

PMID- 21945919
TI  - Cardiologists' educational needs for preventive cardiology in Europe.

PMID- 21945920
TI  - The anesthesia team of the future.
AB  - PURPOSE OF REVIEW: This review is aimed at highlighting the recent developments
      and opportunities that are likely to impact the anesthesia team of the future.
      RECENT FINDINGS: The anesthesia team of the future aims to provide well
      tolerated, efficient, and cost-effective perioperative care. Certified and
      subspecialty trained anesthesiologists lead a diverse team of care providers in
      increasingly dissimilar environments. The spread of electronic health record
      systems has been the basis for the development of clinical decision support
      applications that promise to integrate quality control, enhanced efficiency,
      research opportunities, and improved patient care in the perioperative period.
      Perioperative epidemiology is a likely area of growth within the field of
      anesthesiology ultimately enabling the anesthesia team to translate precise real
      time information into improved outcome. SUMMARY: The anesthesia team of the
      future will require the anesthesiologist to provide expertise across the entire
      domain of perioperative medicine. Meaningful decision support systems rely on
      accurate data analysis and incorporation of current clinical guidelines and
      recommendations.

PMID- 21945921
TI  - Assessing recovery after ambulatory anaesthesia, measures of resumption of
      activities of daily living.
AB  - PURPOSE OF REVIEW: There are several aspects that should be considered when
      measuring the outcome of ambulatory anaesthesia. Major complications and
      admission/readmission rate are classical measures. Fast-track eligible, pain, and
      postoperative nausea and vomiting during the early recovery and time to discharge
      are commonly reported. There is, however, an increasing interest in quality of
      recovery in a more protracted perspective taking various aspects of resumption of
      activities of daily living into account. The aim of the present review is to
      provide an update around postoperative quality of recovery assessment tools.
      Resumption of activities of daily living or defined functional capacities back at
      baseline are measures that provide further insight to the quality of recovery.
      RECENT FINDINGS: There is an increased interest in recovery in a more protracted
      perspective. The Functional Recovery Index is one simple assessment tool
      explicitly developed for measuring recovery after ambulatory anaesthesia. The
      Postoperative Quality of Recovery Scale is a more extensive test developed for
      measuring the recovery after anaesthesia over time in the postoperative period.
      SUMMARY: The quality of recovery in a more protracted perspective, resumption of
      activity of daily living is a measure that needs to be considered in studies of
      perioperative interventions in ambulatory anaesthesia.

PMID- 21945922
TI  - Adherence to exercise programs and determinants of maintenance in older adults
      with mild cognitive impairment.
AB  - After a randomized controlled trial showing that improvement on some aspects of
      cognitive function was related to adherence to an exercise program, determinants
      of adherence and maintenance were further studied. Older adults with mild
      cognitive impairment were contacted 6 mo after the end of exercise programs for a
      telephone interview addressing patterns of adherence and determinants of
      maintenance. Mean adherence during the trial was 53%. About one third of
      participants had lapses during the trial but completed, one third had no lapses,
      and one third dropped out or never started. Practical barriers (time, location)
      were related to not starting and functional limitations to dropout. After the
      trial 25% of participants continued the programs, 14% reported intention to
      continue, and 61% quit. Maintenance was determined by fewer health complaints,
      higher satisfaction with the programs, and better adherence during the programs.
      Although maintenance was low, this study identified several reasons and barriers
      to adherence and maintenance that could be addressed.

PMID- 21945923
TI  - EGFR and KRAS mutations detection on lung cancer liquid-based cytology: a pilot
      study.
AB  - In advanced non-small-cell lung carcinomas epidermal growth factor receptor
      (EGFR) and KRAS testing is often performed on cytology. Liquid-based cytology
      (LBC), which eliminates the need for slide preparation by clinicians, may be very
      useful. In 42 LBC DNA was extracted twice. One sample was obtained directly from
      CytoLyt solution, whereas the other DNA sample was derived after smear
      preparation and laser capture microdissection (LCM) of Papanicolaou-stained
      cells. EGFR and KRAS mutational analyses were performed by direct sequencing. On
      CytoLyt-derived DNA four EGFR (9%) and five KRAS (12%) gene mutations were found.
      When direct sequencing was performed after LCM, the rate of cases that displayed
      either EGFR or KRAS mutations increased from 21% to 40%. Although time-consuming,
      LCM makes direct sequencing highly sensitive even on LBC preparations containing
      only a few cells.

PMID- 21945924
TI  - Infliximab therapy downregulation of basic fibroblast growth factor/syndecan 1
      link: a possible molecular pathway of mucosal healing in ulcerative colitis.
AB  - BACKGROUND: It is known that syndecan 1 in inflammatory bowel diseases is able to
      migrate from epithelial basolateral site to the stromal area and apical surface
      of epithelium with a consequent activation and modulation of basic fibroblast
      growth factor (bFGF), and this process sustains mucosal healing of ulcers. On the
      other hand, tumour necrosis factor (TNF) alpha mucosal levels are directly
      related to the entity of the damage in these disorders. Aim of the study A 'post
      hoc' retrospective study was performed to estimate mucosal TNF alpha in rectal
      biopsies of subjects with ulcerative colitis (UC) before and after effective
      infliximab therapy and its relationship with syndecan 1, bFGF and endoscopic
      mucosal healing. MATERIAL AND METHODS: Paraffin-embedded rectal samples from 12
      patients with UC responders to infliximab were analysed for TNF alpha, syndecan 1
      and bFGF before and 6 months after therapy using a real-time reverse
      transcriptase polymersase chain reaction. Additionally, syndecan 1 location was
      evaluated by immunohistochemistry. Samples from 12 subjects with irritable bowel
      symptoms without endoscopic/histological abnormalities represented the control
      group. Mucosal healing induced by the treatment was defined by an endoscopic Mayo
      subscore changing from 2-3 to 0. ANOVA plus Student-Newman-Keuls was used for
      statistical analysis. RESULTS: The authors found that in the active disease, an
      increase in TNF alpha (p<0.001) is accompanied by raised levels of both syndecan
      1 (p<0.005) and bFGF (p<0.005) compared with the control group. Infliximab
      induced TNF alpha decrease to levels similar to controls is associated with both
      endoscopic mucosal healing and adhesion molecule/growth factor significant
      reduction. Additionally, syndecan 1 location, which is predominant in the stromal
      cells and apical epithelium in the active disorder, is quite exclusively located
      at the basolateral epithelial area in both healed mucosa and controls.
      CONCLUSIONS: Balanced interaction among TNF alpha inhibition by infliximab,
      syndecan 1 migration, bFGF repair modulation and final adhesion molecule reversal
      to its normal location might represent a suitable molecular pathway of endoscopic
      mucosal healing in UC.

PMID- 21945925
TI  - Epidural hematoma associated with occult fracture in ankylosing spondylitis
      patient: a case report and review of the literature.
AB  - STUDY DESIGN: A case report and review of the literature. OBJECTIVE: To highlight
      the risk of occult fracture associated with symptomatic epidural hematoma in
      patient with ankylosing spondylitis. SUMMARY OF BACKGROUND DATA: Hyperextension
      injuries are common in patients with ankylosed spine. Failure of standard imaging
      to detect these fractures may result in delayed diagnosis. Ossification of the
      ligaments in these patients makes even subtle fractures grossly unstable owing to
      the increased lever arm. Delayed diagnosis of fractures may result in further
      displacement and increased risk of neurological injury. METHODS: The clinical
      findings, roentgenographic appearance, and treatment were presented. RESULTS: A
      69-year-old patient with a history of ankylosing spondylitis fell 9 feet from a
      ladder. The patient developed pain in his neck and numbness in his hands. Initial
      computed tomography (CT) scan of spine showed a subtle fracture in the vertebral
      body of C7. A magnetic resonance imaging scan showed an epidural hematoma
      extending from C5 to T3. The patient was taken to the operating room urgently for
      decompression. Laminectomy was performed from C5 to T3 and a large epidural
      hematoma was evacuated. After decompression the patient had some improvement in
      his neurological status. A postdecompression repeat CT scan revealed obvious
      fracture at C6-C7 with anterior distraction indicating a hyperextension injury.
      The patient was taken back to the operating room within 16 hours of his
      decompression for C4 to T3 posterior segment instrumentation and fusion.
      CONCLUSIONS: Patients with ankylosing spondylitis who sustain low-energy injuries
      should be considered to have a fracture especially if they develop epidural
      hematoma. A high index of suspicion is necessary in such a case. Imaging studies
      including magnetic resonance imaging and CT scans should be reviewed carefully to
      rule out any occult fracture.

PMID- 21945926
TI  - Cyclic sciatica in a patient with deep monolateral endometriosis infiltrating the
      right sciatic nerve.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To show by case presentation, the potential
      for endometriosis to infiltrate the somatic nerves causing lower extremity
      neuropathic pain and to discuss possible surgical remedy and the effectiveness of
      laparoscopic neurolysis. SUMMARY OF BACKGROUND DATA: Pelvic endometriosis may
      infiltrate the pelvic wall and somatic nerves causing severe neuropathic
      symptoms. METHODS: We report a case of a 41-year-old woman with a history of
      severe dysmenorrhea, dyspareunia, and chronic pelvic pain with concomitant
      monolateral right sciatica because of deep infiltrating pelvic endometriosis
      involving the sciatic nerve and pelvic wall. RESULTS: The patient was treated by
      laparoscopic neurolysis of the involved somatic nerves according to the Possover
      operation. CONCLUSIONS: Endometriosis is a chronic inflammatory disease,
      potentially infiltrating the somatic nerves. Laparoscopic neurolysis is a
      therapeutic aetiological therapy, which can relieve neurological symptoms
      deriving from nerve infiltration/compression.

PMID- 21945927
TI  - Maternal-child nutrition practices and pediatric overweight/obesity in the United
      States and Chile: a comparative study.
AB  - Childhood overweight/obesity is now epidemic in both developed countries and
      those undergoing economic transition. This study compared maternal and school-age
      child nutrition practices and body mass index in the United States and in Chile.
      Children (125 in the United States, 121 in Chile) and their mothers (116 in the
      United States, 101 in Chile) participated. Findings indicated that child
      nutrition practices were comparable, but mothers in the U.S. group demonstrated
      fewer healthy nutrition practices on behalf of their children. Significant
      associations were found between maternal and child nutrition practices.
      Substantially more children in the U.S. sample were overweight/obese.
      Implications for practice are presented.

PMID- 21945928
TI  - Arsenic bioaccumulation in a marine juvenile fish Terapon jarbua.
AB  - Arsenic (As) is a ubiquitous toxic metalloid that is causing widespread public
      concern. Recent measurements have indicated that some marine fish in China might
      be seriously contaminated with As. Yet the biokinetics and bioaccumulation
      pathway of As in fish remain little understood. In this study, we employed a
      radiotracer technique to quantify the dissolved uptake, dietary assimilation and
      subsequent efflux of As(V) in a marine predatory fish, Terapon jarbua. The
      dissolved uptake of As showed a linear pattern over a range of dissolved
      concentrations from 0.5 to 50 MUg L(-1), with a corresponding uptake rate
      constant of 0.0015 L g(-1)d(-1). The assimilation efficiencies (AEs) of dietary
      As were only 3.1-7.4% for fish fed with copepods, clams, prey fish, or artificial
      diets, and were much lower than the As that entered the trophically available
      metal fraction in the prey. The dietary AEs were independent of the As(V)
      concentrations in the artificial diets. The efflux rate constant of As in fish
      following the dietary exposure was 0.03 d(-1). Modeling calculations showed that
      dietary uptake could be the primary route for As bioaccumulation in fish, and the
      corresponding contributions of waterborne and dietary uptakes were related to the
      bioconcentration factor (BCF) of the prey and the ingestion rate of fish. This
      study demonstrates that As(V) has a low bioavailability to T. jarbua.

PMID- 21945929
TI  - Glucose exposure pattern determines glucagon-like peptide 1 receptor expression
      and signaling through endoplasmic reticulum stress in rat insulinoma cells.
AB  - Repeated fluctuation in plasma glucose levels, as well as chronic hyperglycemia,
      is an important phenomenon frequently observed in diabetic patients. Recently,
      several studies have reported that glucose fluctuation, compared to chronic
      hyperglycemia, mediates more adverse effects due to induced oxidative and/or
      endoplasmic reticulum (ER) stress. In type 2 diabetes, stimulation of insulin
      secretion by glucagon-like peptide-1 (GLP-1) has been found to be reduced, and
      the results of recent studies have shown that the expression of the GLP-1
      receptor (GLP-1R) is reduced by chronic hyperglycemia. However, GLP-1R signaling
      in glucose fluctuation has not been elucidated clearly. In this study, we
      hypothesized that intermittent high glucose (IHG) conditions also reduced GLP-1
      mediated cellular signaling via reduction in GLP-1R expression. To evaluate this
      hypothesis, rat insulinoma cells (INS-1) were exposed for 72 h to either
      sustained high glucose (SHG) conditions (30 mM glucose) or IHG conditions (11 and
      30 mM glucose, alternating every 12h). In comparison to both the SHG and control
      groups, IHG conditions induced a more significant impairment of insulin release
      and calcium influx in response to 1nM GLP-1 treatment. In addition, the activity
      of caspase 3/7 as well as the gene expression of binding protein (Bip) and C/EBP
      homologous protein (CHOP), molecular markers of ER stress, was significantly
      higher in IHG-treated cells than in SHG-treated cells. Interestingly, the
      expression level of GLP-1R was significantly lower under IHG conditions than
      under SHG conditions. Collectively, these findings indicated that glucose
      fluctuation reduces GLP-1R expression through ER stress more profoundly than
      sustained hyperglycemia, which may contribute to the diminished response of GLP
      1.

PMID- 21945930
TI  - Effect of the tyrosine kinase inhibitor lapatinib on CUB-domain containing
      protein (CDCP1)-mediated breast cancer cell survival and migration.
AB  - The surface receptor CUB domain-containing protein 1 (CDCP1) is highly expressed
      in several adenocarcinomas and speculated to participate in anchorage-independent
      cell survival and cell motility. Tyrosine kinase phosphorylation seems to be
      crucial for intracellular signaling of CDCP1. Lapatinib, a tyrosine kinase
      inhibitor (TKI), is approved for treatment of HER-2/neu overexpressing metastatic
      breast cancer and functions by preventing autophosphorylation following HER-2/neu
      receptor activation. This study aimed to investigate the effect of CDCP1
      expression on anchorage-independent growth and cell motility of breast cancer
      cells. Moreover, studies were performed to examine if lapatinib provided any
      beneficial effect on HER-2/neu((+)/-)/CDCP1(+) breast cancer cell lines. In our
      studies, we affirmed that CDCP1 prevents cells from undergoing apoptosis when
      cultured in the absence of cell-substratum anchorage and that migratory and
      invasive properties of these cells were decreased when CDCP1 was down-regulated.
      However, only HER-2/neu(+), but not HER-2/neu((+)/-) cells showed decreased
      proliferation and invasion and an enhanced level of apoptosis towards loss of
      anchorage when treated with lapatinib. Therefore, we conclude that CDCP1 might be
      involved in regulating adhesion and motility of breast cancer cells but that
      lapatinib has no effect on tyrosine kinases regulating CDCP1. Nonetheless, other
      TKIs might offer therapeutic approaches for CDCP1-targeted breast cancer therapy
      and should be studied considering this aspect.

PMID- 21945931
TI  - On photoprotective mechanisms of carotenoids in light harvesting complex.
AB  - Carotenoids in light harvesting complex (LHC) play an important role in
      preventing plants photodamage caused by excess light. Non-photochemical quenching
      (NPQ) is an important mechanism adopted by plants to deal with high light
      intensity and the major component is referred to as energy dependent quenching
      (qE). Despite numerous studies have been devoted to investigating the site and
      mechanism of qE, there are still much debate on these topics. In this article, we
      discussed the possible site and underlying mechanism of qE based on the
      structural similarity of carotenoids. Moreover, being as good antioxidants,
      carotenoids' potential protective effects against LHC photo-oxidation by
      quenching active oxygen species or triplet excited state chlorophyll are also
      discussed.

PMID- 21945932
TI  - Nandrolone reduces activation of Notch signaling in denervated muscle associated
      with increased Numb expression.
AB  - Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The
      molecular mechanisms responsible for this effect are not well understood.
      Androgens and anabolic steroids activate Notch signaling in animal models of
      aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by
      which nandrolone prevents denervation-atrophy, we investigated the effects of
      nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation
      significantly increased Notch activity reflected by elevated levels of nuclear
      Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene).
      Activation was greatest at 7 and 35 days after denervation but remained present
      at 56 days after denervation. Activation of Notch in denervated muscle was
      prevented by nandrolone associated with upregulated expression of Numb mRNA and
      protein. These data demonstrate that denervation activates Notch signaling, and
      that nandrolone abrogates this response associated with increased expression of
      Numb, suggesting a potential mechanism by which nandrolone reduces denervation
      atrophy.

PMID- 21945933
TI  - RLIM interacts with Smurf2 and promotes TGF-beta induced U2OS cell migration.
AB  - TGF-beta (transforming growth factor-beta), a pleiotropic cytokine that regulates
      diverse cellular processes, has been suggested to play critical roles in cell
      proliferation, migration, and carcinogenesis. Here we found a novel E3 ubiquitin
      ligase RLIM which can directly bind to Smurf2, enhancing TGF-beta responsiveness
      in osteosarcoma U2OS cells. We constructed a U2OS cell line stably over
      expressing RLIM and demonstrated that RLIM promoted TGF-beta-driven migration of
      U2OS cells as tested by wound healing assay. Our results indicated that RLIM is
      an important positive regulator in TGF-beta signaling pathway and cell migration.

PMID- 21945935
TI  - Molecular design of new sodium channel blockers.
AB  - Animal toxins targeting voltage-gated sodium channels (VGSCs) have been
      considered as valuable tools for studying pharmacological functions of VGSCs.
      Recently we have reported that Drosotoxin (DrTx), an evolution-guided chimeric
      peptide, exhibits highly selective blocking activity to tetrodotoxin-resistant
      (TTX-R) Na(+) channels in rat dorsal root ganglion (DRG) neurons. In this study,
      we constructed five new analogues of DrTx designed by altering amino-terminal
      sequences of DrTx, two of which have significant inhibitory effects on both TTX-R
      and tetrodotoxin-sensitive (TTX-S) Na(+) channels. Structure-activity
      relationship studies allow us to recognize key functional roles of a positive
      charge at site seven and a negative charge at site eight in evolving new blocking
      activity to TTX-S sodium channels. This work will enhance our understanding of
      the molecular determinants of toxins affecting VGSCs and aid the rational design
      of subtype-specific blockers of the channels.

PMID- 21945934
TI  - Leptin boosts cellular metabolism by activating AMPK and the sirtuins to reduce
      tau phosphorylation and beta-amyloid in neurons.
AB  - Leptin is a pleiotropic hormone primarily secreted by adipocytes. A high density
      of functional Leptin receptors has been reported to be expressed in the
      hippocampus and other cortical regions of the brain, the physiological
      significance of which has not been explored extensively. Alzheimer's disease (AD)
      is marked by impaired brain metabolism with decreased glucose utilization in
      those regions which often precede pathological changes. Recent epidemiological
      studies suggest that plasma Leptin is protective against AD. Specifically,
      elderly with plasma Leptin levels in the lowest quartile were found to be four
      times more likely to develop AD than those in the highest quartile. We have
      previously reported that Leptin modulates AD pathological pathways in vitro
      through a mechanism involving the energy sensor, AMP-activated protein kinase
      (AMPK). To this end, we investigated the extent to which activation of AMPK as
      well as another class of sensors linking energy availability to cellular
      metabolism, the sirtuins (SIRT), mediate Leptin's biological activity. Leptin
      directly activated neuronal AMPK and SIRT in cell lines. Additionally, the
      ability of Leptin to reduce tau phosphorylation and beta-amyloid production was
      sensitive to the AMPK and sirtuin inhibitors, compound C and nicotinamide,
      respectively. These findings implicate that Leptin normally acts as a signal for
      energy homeostasis in neurons. Perhaps Leptin deficiency in AD contributes to a
      neuronal imbalance in handling energy requirements, leading to higher Abeta and
      phospho-tau, which can be restored by replenishing low Leptin levels. This may
      also be a legitimate strategy for therapy.

PMID- 21945936
TI  - Differential adenosine uptake in mixed neuronal/glial or purified glial cultures
      of avian retinal cells: modulation by adenosine metabolism and the ERK cascade.
AB  - Adenosine is an important modulator of neuronal survival and differentiation in
      the CNS. Our previous work showed that nucleoside transporters (NTs) are present
      in cultures of chick retinal cells, but little is known about the mechanisms
      regulating adenosine transport in these cultures. Our aim in the present work was
      to study the participation of the adenosine metabolism as well as the ERK pathway
      on adenosine uptake in different types of retinal cultures (mixed and purified
      glial cultures). Kinetic analysis in both cultures revealed that the uptake
      reached equilibrium after 30 min and presented two components. Incubation of
      cultures with S-(p-nitrobenzyl)-6-thioinosine (NBTI) or dipyridamole, different
      inhibitors of equilibrative nucleoside transporters (ENTs), produced a
      significant and concentration-dependent uptake reduction in both cultures.
      However, while dipyridamole presented similar maximal inhibitory effects in both
      cultures (although in different concentrations), the inhibition by NBTI was
      smaller in glial cultures than in mixed cultures, suggesting the presence of
      different transporters. Moreover, pre-incubation of [(3)H]-adenosine with
      adenosine deaminase (ADA) or adenosine kinase (ADK) inhibition with
      iodotubercidin promoted significant uptake inhibition in both cultures,
      indicating that the uptake is predominantly for adenosine and not inosine, and
      that taken up adenosine is preferentially directed to the synthesis of adenine
      nucleotides. In both cultures, the MEK inhibitors PD98059 or UO126, but not the
      inactive analog U0124, induced a significant and concentration-dependent uptake
      decrease. We have not observed any change in adenosine metabolism induced by MEK
      inhibitors, suggesting that this pathway is mediating a direct effect on NTs. Our
      results show the expression of different NTs in retinal cells in culture and that
      the activity of these transporters can be regulated by the ERK pathway or
      metabolic enzymes such as ADK which are then potential targets for regulation of
      Ado levels in normal or pathological conditions.

PMID- 21945938
TI  - Rhomboid-7 over-expression results in Opa1-like processing and malfunctioning
      mitochondria.
AB  - Rhomboid-7 (rho-7) is a mitochondrial-specific intramembranous protease. The loss
      of-function mutation rho-7 results in semi-lethality, while escapers have a
      reduced lifespan with several neurological disorders [1]. Here we show that
      general, or CNS-specific expression of rho-7 can rescue the lethality of rho-7.
      General, or CNS-specific over-expression of rho-7 in otherwise wild-type animals
      caused semi-lethality, with approximately 50% of the animals escaping this
      lethality, developing into adults displaying a shortened life span with larval
      locomotory problem. On a cellular level, over-expression resulted in severe
      depression of ATP levels and cytochrome c oxidase subunit II mRNA levels, a
      lowered number of mitochondria in neurons and aggregation of mitochondria in the
      brain indicating mitochondrial malfunction. Over-expression of rho-7 in
      developing eye discs resulted in an elevated apoptotic index. In the CNS,
      elevated levels of rho-7 were accompanied by both isoforms of Opa1-like, a
      dynamin-like GTPase, a mitochondrial component involved in regulating
      mitochondrial dynamics and function, including apoptosis. Most, but not all, of
      rho-7 over-expression phenotypes were suppressed by introducing a heterozygous
      mutation for Opa1-like. Our results suggest that rho-7 and Opa1-like function in
      a common molecular pathway affecting mitochondrial function and apoptosis in
      Drosophila melanogaster.

PMID- 21945937
TI  - Loss-of-function of ACVR1 in osteoblasts increases bone mass and activates
      canonical Wnt signaling through suppression of Wnt inhibitors SOST and DKK1.
AB  - BMPs (Bone morphogenetic proteins) such as BMP2 and BMP7 have been used about one
      decade as bone anabolic agents in orthopaedics. The BMP receptor ACVR1, which is
      a key receptor of BMP7, is expressed in bone. The pathological role of ACVR1 in
      humans has been reported: a point mutation in ACVR1 can cause fibrodysplasia
      ossificans progressiva (FOP) in which ectopic ossification occurs in skeletal
      muscles and deep connective tissues. The physiological function of ACVR1 in bone,
      however, is totally unknown. The purpose of this study is to investigate the
      endogenous role of ACVR1 in osteoblasts, one of the most dominant cell-types in
      bone. We generated Acvr1-null mice in an osteoblast-specific manner using an
      inducible Cre-loxP system. Surprisingly, we found that bone mass was increased in
      the Acvr1-null mice. Interestingly, canonical Wnt signaling was increased and
      expression levels of Wnt inhibitors Sost and Dkk1 were both suppressed in the
      null bones during the developmental stages. In addition, we confirmed that
      expression levels of both Sost and Dkk1 were upregulated by BMP7 dose-dependently
      in vitro. These results suggest that the Acvr1-deficiency can increase bone mass
      by activating Wnt signaling in which both Sost and Dkk1 expression levels are
      diminished. This study leads to a new concept of the BMP7-ACVR1-SOST/DKK1 axis in
      osteoblasts, in which BMP7 signaling through ACVR1 can reduce Wnt signaling via
      SOST/DKK1 and then inhibits osteogenesis. Although this concept is beyond the
      current known function of BMP7, it can explain the varied outcomes of BMP7
      treatment. We believe BMP signaling can exhibit multifaceted effects by context
      and cell type.

PMID- 21945939
TI  - Evaluation of human LOX-12 as a serum marker for breast cancer.
AB  - The high concentration of prostaglandins has been associated with chronic
      inflammatory diseases and several types of human cancers. This is due to the over
      expression of inflammatory enzymes like Cyclooxygenase (COX), Lipoxygenase (LOX)
      etc. The aim of this study was to quantify the LOX-12 with clinicopathological
      parameter of breast cancer patients and its response after chemotherapy to
      establish serum LOX-12 as a prognostic marker. This case-controlled study was
      performed on 86 biopsy proven breast cancer patients. Blood and tissue samples
      were collected from the patients. Serum LOX-12 of the study group was quantified
      by Surface Plasmon Resonance (SPR) and ELISA techniques by antibody-antigen
      interaction strategy. A significant increase in LOX-12 levels was observed in
      breast cancer patients (Mean +/- SD=40.54+/-13.61 ng/ml) as compared to healthy
      controls (Mean +/- SD=13.42+/-2.4 ng/ml) (p<0.0001). Serum LOX-12 levels were
      significantly higher (p<0.002) in patients with lymph node involvement. More than
      75% patients had shown significant (p<0.0001) reduction of LOX-12 levels after
      chemotherapy. This was also confirmed by ELISA. This study for the first time had
      co-related the quantity of serum LOX-12 with breast cancer and also with the
      effect of chemotherapy.

PMID- 21945940
TI  - Phosphorylation of VASP by AMPK alters actin binding and occurs at a novel site.
AB  - Vasodilator-stimulated phosphoprotein (VASP) is an actin regulatory protein that
      functions in adhesion and migration. In epithelial cells, VASP participates in
      cell-cell adhesion. At the molecular level, VASP drives actin bundling and
      polymerization. VASP activity is primarily regulated by phosphorylation. Three
      physiologically relevant phosphorylation sites significantly reduce actin
      regulatory activity and are targeted by several kinases, most notable Abl and
      protein kinases A and G (PKA and PKG). AMP-dependent kinase (AMPK) is best
      characterized as a cellular sensor of ATP depletion, but also alters actin
      dynamics in epithelial cells and participates in cell polarity pathways
      downstream of LKB1. While little is known about how AMPK direct changes in actin
      dynamics, AMPK has been shown to phosphorylate VASP at one of these three well
      characterized PKA/PKG phosphorylation sites. Here we show that phosphorylation of
      VASP by AMPK occurs at a novel site, serine 322, and that phosphorylation at this
      site alters actin filament binding. We also show that inhibition of AMPK activity
      results in the accumulation of VASP at cell-cell adhesions and a concomitant
      increase in cell-cell adhesion.

PMID- 21945941
TI  - The suitability of concentration addition for predicting the effects of multi
      component mixtures of up to 17 anti-androgens with varied structural features in
      an in vitro AR antagonist assay.
AB  - The risks associated with human exposures to chemicals capable of antagonising
      the effects of endogenous androgens have attracted considerable recent interest.
      Exposure is typically to large numbers of chemicals with androgen receptor (AR)
      antagonist activity, yet there is limited evidence of the combined effects of
      multi-component mixtures of these chemicals. A few in vitro studies with mixtures
      of up to six AR antagonists suggest that the concept of concentration addition
      (CA) provides good approximations of experimentally observed mixture effects, but
      studies with larger numbers of anti-androgens, and with more varied structural
      features, are missing. Here we show that the mixture effects of up to 17 AR
      antagonists, comprising compounds as diverse as UV-filter substances, parabens,
      perfluorinated compounds, bisphenol-A, benzo(alpha)pyrene, synthetic musks,
      antioxidants and polybrominated biphenyls, can be predicted well on the basis of
      the anti-androgenicity of the single components using the concept of CA. We
      tested these mixtures in an in vitro AR-dependent luciferase reporter gene assay,
      based on MDA-kb2 cells. The effects of further mixtures, composed of four and six
      anti-androgens, could be predicted accurately by CA. However, there was a
      shortfall from expected additivity with a ten-component mixture at two different
      mixture ratios, but attempts to attribute these deviations to differential
      expression of hormone-metabolising CYP isoforms did not produce conclusive
      results. CA provides good approximations of in vitro mixture effects of anti
      androgens with varying structural features.

PMID- 21945942
TI  - The association of natural elements with physical activity intensity during trail
      use by older adults.
AB  - BACKGROUND: Public health efforts to promote trail use among older adults could
      be an effective strategy for increasing physical activity among older adults.
      However, research is needed to better understand factors that influence older
      adults' use of trails. PURPOSE: To examine the association between variations in
      natural elements (ie, season, weather, temperature) and older adults' overall
      trail use and physical activity intensity during trail use. METHODS: A rail-trail
      in South Carolina was systematically evaluated (2006-2009) using The System for
      Observing Play and Recreation in Communities. RESULTS: The majority (74.2%) of
      the 1053 older trail users observed were walking; 25.9% were observed in vigorous
      activity. Older adults were most often observed using the trail in the spring
      (40.1%), sunny weather (76.8%), and moderate temperatures (56.2%). Significant
      differences in activity type by natural element variables were identified.
      CONCLUSIONS: When promoting trail use among older adults, natural elements should
      be considered.

PMID- 21945943
TI  - Effects of handling regime and sex on changes in cortisol, thyroid hormones and
      body mass in fasting grey seal pups.
AB  - Survival of seal pups may be affected by their ability to respond appropriately
      to stress. Chronic stress can adversely affect secretion of cortisol and thyroid
      hormones, which contribute to the control of fuel utilisation. Repeated handling
      could disrupt the endocrine response to stress and/or negatively impact upon mass
      changes during fasting. Here we investigated the effects of handling regime on
      cortisol and thyroid hormone levels, and body mass changes, in fasting male and
      female grey seal pups (Halichoerus grypus). Females had higher thyroid hormone
      levels than males throughout fasting and showed a reduction in cortisol midway
      through the fast that was not seen in males. This may reflect sex-specific fuel
      allocation or development. Neither handling frequency nor cumulative contact time
      affected plasma cortisol or thyroid hormone levels, the rate of increase in
      cortisol over the first five minutes of physical contact or the pattern of mass
      loss during fasting in either sex. The endocrine response to stress and the
      control of energy balance in grey seal pups appear to be robust to repeated,
      short periods of handling. Our results suggest that routine handling should have
      no additional impact on these animals than general disturbance caused by
      researchers moving around the colony.

PMID- 21945944
TI  - Urinary organic anion transporter protein profiles in AKI.
AB  - BACKGROUND: Organic anion transporters (OATs) are located on either the
      basolateral or the apical membrane of the proximal tubule cell and mediate the
      absorption and secretion of various drugs and endogenous metabolites. It has been
      shown that cellular damage in acute kidney injury (AKI) involves three forms of
      injury: sublethal damage resulting in loss of cell polarity, cell death through
      apoptosis and necrosis. We hypothesize that cellular mistargeting of OAT proteins
      in AKI will change the profile of OAT proteins in urine. METHODS: Thirty AKI
      patients were included in the study. AKI was defined by clinical course, daily
      urine output, response to fluid repletion, urinary sediment, fractional excretion
      of sodium (FeNa) and urine osmolality. Urinary OAT1, OAT3 and OAT4 protein
      abundance was measured from semiquantitative immunoblots of urine membrane
      fraction samples (exosome) collected from patients with AKI and from control
      subjects. RESULTS: Although all patients studied reached a similar severity of
      renal failure measured by serum creatinine, some of them recovered from AKI with
      supportive care only, while others required renal replacement therapy (RRT). OAT1
      and OAT3, which are normally localized in the basolateral membrane of the
      proximal tubule cell, were detected at low levels in urine from control subjects
      and were increased significantly in all patients with AKI. OAT4 protein, which is
      normally localized in the luminal membrane of proximal tubule cells, was present
      in abundance in urine of control subjects. Interestingly, in patients with AKI
      who eventually recovered, urinary OAT4 was found to be significantly lower than
      in controls, while in patients who needed RRT, it was higher than in controls.
      CONCLUSIONS: We have shown that OATs are mistargeted in AKI. The urinary OAT
      protein profile can help us to learn about the pathophysiology of the disease and
      might be a marker of AKI severity. AKI patients with early reversible proximal
      tubular damage will have high urine OAT1 and OAT3 and low OAT4, while patients
      with severe AKI will have high urine OAT1, OAT3 and OAT4.

PMID- 21945945
TI  - Relativity and the kidney: observations regarding glomerular density.

PMID- 21945946
TI  - Place conditioning and neurochemical responses elicited by the aftereffect of
      acute stressor exposure involving an elevated stand.
AB  - Acute exposure to an elevated stand has been used as an inescapable mild stressor
      for rats. The present study examined the effects of this stressor using a place
      conditioning behavioral test and neurochemical assays of dopamine and its
      metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), in the medial prefrontal
      cortex and nucleus accumbens. The behavioral data showed that a conditioned place
      preference was formed as an aftereffect of the elevated stand stressor. In a
      separate experiment, neurochemical assay showed an immediate increase of dopamine
      in the nucleus accumbens after 30min exposure to the elevated stand stressor. In
      addition, the DOPAC content in the nucleus accumbens was significantly increased
      at 30min after this stressor. No significant change in dopamine or DOPAC levels
      in the medial prefrontal cortex was detected for up to 60min after stressor
      manipulation. These results suggest that an increase in dopamine activity in the
      nucleus accumbens is involved in the development of conditioned place preference
      elicited by the aftereffects of the elevated stand stressor.

PMID- 21945947
TI  - Neuroprotective effects of Kv7 channel agonist, retigabine, for cisplatin-induced
      peripheral neuropathy.
AB  - Chemotherapy-induced peripheral neuropathy is a major dose-limiting side effect
      of many commonly used chemotherapeutic agents. One mechanism underlying this
      neuronal damage is via drug-induced membrane depolarization. Accordingly, one
      potential approach for preventing chemotherapy-induced neuropathy is via the
      forced maintenance of normal membrane potential during exposure to the toxic
      drug. More specifically, intentional elevation of the slow K(+) current, via
      activation of Kv7 channels with a resultant hyperpolarizing shift, could be
      theoretically neuroprotective. In this study, in vivo nerve excitability testing
      in sensory nerves in mice was used to evaluate the potential therapeutic role of
      retigabine, a Kv7 channel activator, in the prevention of cisplatin-induced
      neurodegeneration. It was found that cisplatin caused membrane depolarization and
      peripheral axon loss that were partially prevented by retigabine pretreatment.
      These results support the general concept that chemotherapy-induced neuropathy
      can be partially inhibited via Kv7 channel activation.

PMID- 21945948
TI  - Feedback from area 21a influences orientation but not direction maps in the
      primary visual cortex of the cat.
AB  - In the monkey's visual cortex, there are two well-documented information
      processing streams: the dorsal motion and ventral form/color pathways. Similarly,
      two corresponding information streams were also found in the cat's visual
      cortices, and PMLS and area 21a are the gateways for distinct motion and form
      information processing. It has been shown that the feedback from PMLS solely
      modulates motion direction, but not orientation response, while the feedback from
      area 21a modulates form related features, such as spatial frequency dependency
      and neuronal oblique effect. Here, we postulate that feedback signals from higher
      cortical areas in the form or the motion information pathway may solely modulate
      the corresponding properties in neurons in the lower areas of the visual system.
      To examine the above hypothesis, the impact of feedback from higher area 21a on
      both orientation and direction maps was investigated in area 17 of the cat using
      intrinsic signal optical imaging. The results showed that the feedback from area
      21a did not affect the amplitude and preference of direction, but did modulate
      orientation response in area 17, supporting the above hypothesis.

PMID- 21945949
TI  - Neuroprotective and anti-stress effect of A68930 in acute and chronic
      unpredictable stress model in rats.
AB  - The neurorescuing effect of A68930 (a potent selective D(1) agonist) and its role
      on the regulation of hypothalamus-pituitary-adrenal (HPA)-axis have been
      investigated. Acute (AS) and chronic unpredictable (CUS) stress models were used
      to evaluate the effect of A68930 on HPA-axis regulation in relation to the change
      in the fiber density and number of immunoreactive (ir) neurons of tyrosine
      hydroxylase (TH) and glucocorticoid receptor (GR) in the dopamine (DA) and GR
      rich brain regions in rats. CUS caused a significant decrease in the number of TH
      ir neurons in the striatum, medial forebrain bundle, ventral tegmental area and
      substansia nigra and GR in the cortex, striatum and hippocampus as compared to
      the non-stress controls (NS). Administration of A68930 (0.25mg/kg i.p.)
      significantly normalized these CUS-induced alterations. We also examined the role
      of A68930 on stress-induced brain oxidative status. AS enhanced the activities of
      superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the cortex and
      striatum, while CUS reduced the activities of SOD and catalase (CAT) in the
      cortex, striatum and hippocampus, when compared with NS. Increased GSH-Px
      activity, with reduced glutathione and increased lipid peroxidation was observed
      in both AS and CUS in selected brain regions as compared to NS. Administration of
      A68930 normalized the antioxidant enzyme activities, replenished GSH and
      decreased the extent of lipid peroxidation. In conclusion, present findings
      suggest that the stress-induced immunoreactivity of TH and GR in distinct brain
      regions are modulated by A68930 leading to the normalization of HPA-axis
      response. Ours results show the therapeutic importance of DA D(1) agonist in
      stress-induced dopaminergic-related neurological disorders. A68930 also
      influenced the brain antioxidant machinery probably through the restoration of
      stress-induced changes in the dopaminergic system and its crosstalk with GR.

PMID- 21945950
TI  - Effect of recombinant human growth hormone on peripheral nerve regeneration:
      experimental work on the ulnar nerve of the rat.
AB  - Neurotrophic factors may be used to improve the growth and repair of injured
      peripheral nerves. In this study we determined the effectiveness of recombinant
      human growth hormone on peripheral nerve injury in the Wistar rat. The ulnar
      nerve of the rat was sectioned and its proximal and distal ends were sutured to
      either end of a silastic tube, with the aim of encouraging regeneration through
      the tube. 32 ulnar nerve specimens were randomized into two groups: 18 nerves
      regenerating under the influence of recombinant growth hormone, and 14 nerves
      regenerating in its absence. The study was performed over a period of 8 weeks and
      progression of regeneration was assessed with regular surface electroneurography
      every 1-2 weeks after surgery. In the group receiving recombinant growth hormone,
      it comprised a significant improvement in the recovery of conduction velocity,
      and a more gradual increase in the amplitude of motor potential from the fifth
      week onwards was observed. Histological analysis of study specimens in the
      recombinant hormone group revealed an improved architecture of the regenerating
      nerve, a greater density of nerve fibers, and increased myelination with a lesser
      degree of endoneural fibrosis. Our work demonstrates the positive effect of the
      administration of recombinant human growth hormone in obtaining significantly
      improved conduction velocities, and a greater improvement in nerve regeneration
      from the fifth week of monitoring when compared to the control group.
      Histological analysis in the group receiving hormone showed acceptable degree of
      myelination with little granulation tissue and fibrosis.

PMID- 21945951
TI  - The activation of the p53 pathway by the AMP mimetic AICAR is reduced by
      inhibitors of the ATM or mTOR kinases.
AB  - A balanced diet reduces the risk of life-threatening diseases such as diabetes
      and cancer. A reduced supply of energy at the cellular level leads to an
      increased concentration of AMP, which, in turn, results in LKB1-mediated
      activation of the AMPK kinase. The activation of the p53 tumor suppressor protein
      by metabolic stress has been shown to be mediated by AMPK. Increased
      intracellular AMP can be mimicked by 5-aminoimidazole-4-carboxamide
      ribonucleoside (AICAR). We showed that AICAR activated the p53 pathway in LKB1
      deficient cells. This activation was strongly attenuated by two inhibitors of the
      ATM kinase (caffeine and Ku-55933), which is dysfunctional in ataxia
      telanagiectasia patients. In cells with ATM expression silenced by shRNA, AICAR
      induced p53 phosphorylation at Ser(15) and Ser(37) was attenuated. Furthermore,
      p53 activation by AICAR was blocked by rapamycin, a specific inhibitor of the
      mTOR kinase, which is a crucial regulator of cell growth. Rapamycin did not block
      p53 activation by resveratrol, which, in contrast to AICAR, induced the DNA
      damage response, senescence-like growth inhibition, a high level of post
      translational modification of p53, and weak upregulation of MDM2 (the negative
      regulator of p53). Thus, ATM and mTOR participate in the activation of p53 in
      response to a compound mimicking metabolic stress.

PMID- 21945952
TI  - Effects of islet neogenesis-associated protein pentadecapeptide on cell mass and
      insulin secretion of pancreatic beta-cells.
AB  - OBJECTIVE: To explore the effects of islet neogenesis- associated protein
      pentadecapeptide (INGAP-PP) on proliferation and secretion function of beta
      cells. METHODS: Islets of adult Sprague Dawley rats were isolated by collagenase
      digestion and treated with 10 MUg/ml INGAP-PP, after 12, 24, 48 h, glucose
      stimulated insulin secretion (GSIS) and acridine orange/pro pidium iodide (AO/PI)
      staining were used to detect the secretion function and cell viability. The INS-1
      cells were treated with 0, 1, 10, 25, 50, 100, 250, and 500 MUg/ml INGAP-PP for
      24 or 48 h, MTT cell proliferation assay was adopted to survey the dose-response
      relationship between INGAP-PP and cell proliferation. The mRNA expression of
      roliferating cell nuclear antigen (PCNA), Cyclin D1, Cdk4, P27, p38MAPK, and JNK
      in INS-1 cells were examined by RT-PCR, and the protein expression of PCNA was
      examined by Western blot. The statistical significance was determined by
      Student's t-test or one-way analysis of variance. RESULTS: The insulin secreted
      by islets and the cell viability were increased by INGAP-PP. MTT indicated a dose
      response relationship between INGAP-PP and quantity of INS-1 cells, and treatment
      for 48 h had a stronger effect on cell proliferation than the 24 h. INGAP-PP up
      regulated the mRNA expression of PCNA, Cyclin D1, Cdk4 and downregulated P27,
      p38MAPK, and JNK. Moreover, the protein expression of PCNA was up-regulated by
      45% after INGAPPP exposure for 48 h. CONCLUSIONS: INGAP-PP increased the insulin
      secretion, enhanced the proliferation and might reduce apop tosis of beta-cells.
      The mechanism may contribute to the changed expression of some genes related to
      cell cycle.

PMID- 21945953
TI  - Maintenance of remission among patients with Crohn's disease on antimetabolite
      therapy after infliximab therapy is stopped.
AB  - BACKGROUND & AIMS: It is important to determine whether infliximab therapy can be
      safely interrupted in patients with Crohn's disease who have undergone a period
      of prolonged remission. We assessed the risk of relapse after infliximab therapy
      was discontinued in patients on combined maintenance therapy with antimetabolites
      and identified factors associated with relapse. METHODS: We performed a
      prospective study of 115 patients with Crohn's disease who were treated for at
      least 1 year with scheduled infliximab and an antimetabolite and had been in
      corticosteroid-free remission for at least 6 months. Infliximab was stopped, and
      patients were followed up for at least 1 year. We associated demographic,
      clinical, and biologic factors with time to relapse using a Cox model. RESULTS:
      After a median follow-up period of 28 months, 52 of the 115 patients experienced
      a relapse; the 1-year relapse rate was 43.9% +/- 5.0%. Based on multivariable
      analysis, risk factors for relapse included male sex, the absence of surgical
      resection, leukocyte counts >6.0 * 10(9)/L, and levels of hemoglobin <=145 g/L, C
      reactive protein >=5.0 mg/L, and fecal calprotectin >=300 MUg/g. Patients with no
      more than 2 of these risk factors (approximately 29% of the study population) had
      a 15% risk of relapse within 1 year. Re-treatment with infliximab was effective
      and well tolerated in 88% of patients who experienced a relapse. CONCLUSIONS:
      Approximately 50% of patients with Crohn's disease who were treated for at least
      1 year with infliximab and an antimetabolite agent experienced a relapse within 1
      year after discontinuation of infliximab. However, patients with a low risk of
      relapse can be identified using a combination of clinical and biologic markers.

PMID- 21945954
TI  - Strong transthyretin immunostaining:  potential pitfall in cardiac amyloid
      typing.
AB  - Although systemic amyloidosis commonly presents with renal disease, cardiac
      involvement usually determines the patient's prognosis. Cardiac involvement is
      seen in light chain amyloid and transthyretin amyloidosis. Distinguishing between
      these two is critical because prognosis and treatment differ. Our study
      demonstrates the unreliability of transthyretin immunostaining in subtyping
      cardiac amyloid. Between January 2003 and August 2010, we retrieved 229 native
      endomyocardial biopsies, of which 24 had amyloid. Immunohistochemistry for kappa,
      lambda, transthyretin, and serum amyloid A protein was performed on formalin
      fixed, paraffin-embedded sections. Staining was graded as weak (trace to 1+) or
      strong (2 to 3+). Mass spectrometry (MS)-based proteomic typing of microdissected
      amyloid material was performed on selected cases. Fifteen patients had monoclonal
      gammopathy/plasma cell dyscrasia with cardiac amyloid. Eight of them (53%) showed
      strong transthyretin staining in the cardiac amyloid deposits. MS was performed
      in 5 of these 8 biopsies, and all 5 biopsies revealed light chain amyloid-type
      amyloid. Two of these 5 light chain amyloid biopsies did not even have
      concomitant strong staining for the appropriate light chain. Among the 15 cases
      with plasma cell dyscrasia, only 7 biopsies showed strong staining for the
      corresponding monoclonal light chain. Strong, false-positive immunostaining for
      transthyretin in cardiac amyloid is a potential pitfall, augmented by the
      frequent lack of staining for immunoglobulin light chains. Therefore, the
      presence of amyloid in the cardiac biopsy should prompt a search for plasma cell
      dyscrasia irrespective of transthyretin staining. Confirmation with MS should be
      sought, particularly if there is any discrepancy between kappa/lambda staining
      and serum immunofixation results.

PMID- 21945955
TI  - Somatic mutations in PIK3CA and activation of AKT in intraductal tubulopapillary
      neoplasms of the pancreas.
AB  - Intraductal tubulopapillary neoplasm (ITPN) is a recently recognized rare variant
      of intraductal neoplasms of the pancreas. Molecular aberrations underlying the
      neoplasm remain unknown. We investigated somatic mutations in PIK3CA, PTEN, AKT1,
      KRAS, and BRAF. We also investigated aberrant expressions of phosphorylated AKT,
      phosphatase and tensin homolog (PTEN), tumor protein 53 (TP53), SMAD4, and CTNNB1
      in 11 cases of ITPNs and compared these data with those of 50 cases of
      intraductal papillary mucinous neoplasm (IPMN), another distinct variant of
      pancreatic intraductal neoplasms. Mutations in PIK3CA were found in 3 of 11 ITPNs
      but not in IPMNs (P = 0.005; Fisher exact test). In contrast, mutations in KRAS
      were found in none of the ITPNs but were found in 26 of the 50 IPMNs (P = 0.001;
      Fisher exact test). PIK3CA mutations were associated with strong expression of
      phosphorylated AKT (P < 0.001; the Mann-Whitney U test). Moreover, the expression
      of phosphorylated AKT was apparent in most ITPNs but only in a few IPMNs (P <
      0.001; the Mann-Whitney U test). Aberrant expressions of TP53, SMAD4, and CTNNB1
      were not statistically different between these neoplasms. Mutations in PIK3CA and
      the expression of phosphorylated AKT were not associated with age, sex, tissue
      invasion, and patients' prognosis in ITPNs. These results indicate that
      activation of the phosphatidylinositol 3-kinase pathway may play a crucial role
      in ITPNs but not in IPMNs. In contrast, the mutation in KRAS seems to play a
      major role in IPMNs but not in ITPNs. The activated phosphatidylinositol 3-kinase
      pathway may be a potential target for molecular diagnosis and therapy of ITPNs.

PMID- 21945957
TI  - Acute pancreatitis due to hypercalcemia related to bone metastasis from breast
      cancer.

PMID- 21945959
TI  - The cost-effectiveness of rotavirus vaccination in Armenia.
AB  - The cost-effectiveness of introducing infant rotavirus vaccination in Armenia in
      2012 using Rotarix(R) was evaluated using a multiple birth cohort model. The
      model considered the cost and health implications of hospitalisations, primary
      health care consultations and episodes not leading to medical care in children
      under five years old. Rotavirus vaccination is expected to cost the Ministry of
      Health $220,000 in 2012, rising to $830,000 in 2016 following termination of GAVI
      co-financing, then declining to $260,000 in 2025 due to vaccine price maturity.
      It may reduce health care costs by $34,000 in the first year, rising to $180,000
      by 2019. By 2025, vaccination may be close to cost saving to the Ministry of
      Health if the vaccine purchase price declines as expected. Once coverage has
      reached high levels, vaccination may prevent 25,000 cases, 3000 primary care
      consultations, 1000 hospitalisations and 8 deaths per birth cohort vaccinated.
      The cost per disability-adjusted life year (DALY) saved is estimated to be about
      $650 from the perspective of the Ministry of Health, $850 including costs accrued
      to both the Ministry and to GAVI, $820 from a societal perspective excluding
      indirect costs and $44 from a societal perspective including indirect costs.
      Since the gross domestic product per capita of Armenia in 2008 was $3800,
      rotavirus vaccination is likely to be regarded as "very cost-effective" from a
      WHO standpoint. Vaccination may still be "very cost-effective" if less favourable
      assumptions are used regarding vaccine price and disease incidence, as long as
      DALYs are not age-weighted.

PMID- 21945958
TI  - Improving immunogenicity of HIV-1 envelope gp120 by glycan removal and immune
      complex formation.
AB  - HIV-1 envelope (Env) gp120 is an important target for neutralizing antibody (Ab)
      responses against the virus; however, developing gp120 vaccines that elicit
      potent and broad neutralizing Abs has proven to be a formidable challenge.
      Previously, removal of an N-linked glycan at residue 448 by an N to Q mutation
      (N448Q) has been found to enhance the in vitro antigenicity of neutralizing
      epitopes in the V3 loop. In this study the mutated gp120 was first compared with
      wild type gp120 for immunogenicity in mice using a DNA prime and protein boost
      immunization regimen. The N448Q mutant did not elicit higher titers of anti-gp120
      serum Abs and failed to generate anti-V3 Abs. The sera also had no virus
      neutralizing activity, even though the mutant induced higher levels of
      lymphoproliferation and cytokine production. Subsequently, the N448Q mutant was
      used to construct an immune complex vaccine with the anti-CD4 binding site
      monoclonal antibody (mAb) 654. The N448Q/654 complex stimulated comparably high
      levels of serum Abs to gp120 and V3 as the wild type complex. However, Abs
      against the C1 and C2 regions in the gp120 core were more elevated. Importantly,
      the mutant complex also elicited higher titers of neutralizing Abs activity than
      the wild type counterpart. Similar results were achieved with a complex made with
      gp120 bearing an N448E mutation, confirming the importance of the N448-linked
      glycan in modulating gp120 immunogenicity. Neutralizing activity was directed to
      V3 and other undefined neutralizing epitopes. Improved immunogenicity of the
      immune complexes correlated with alterations in exposure of V3 and other Ab
      epitopes and their stability against proteases. These data demonstrate the
      advantage of combining site-specific N-glycan removal and immune complex
      formation as a novel vaccine strategy to improve immunogenicity of targeted Ab
      epitopes on critical regions of HIV-1 gp120.

PMID- 21945960
TI  - Changes in serotype distribution of Haemophilus influenzae meningitis isolates
      identified through laboratory-based surveillance following routine childhood
      vaccination against H. influenzae type b in Brazil.
AB  - Following routine childhood vaccination against Haemophilus influenzae type b
      (Hib) disease in Brazil in 1999, passive laboratory surveillance reported
      increasing numbers of non-b serotypes and nontypeable H. influenzae (NTHi) from
      meningitis cases. To characterize this increase, we analyzed data on 3910 H.
      influenzae isolated from cerebrospinal fluid or blood from meningitis cases that
      were sent to the national reference laboratory for serotyping from 1990 to 2008.
      Hib accounted for 98% of H. influenzae meningitis isolates received during 1990
      1999 versus 59% during 2000-2008, while non-b serotypes increased from 1% to 19%
      and NTHi increased from 2% to 22% of H. influenzae isolates received during the
      two periods. Higher proportions of non-b serotypes and NTHi than Hib were
      isolated from blood rather than cerebrospinal fluid. Estimated incidence rates
      for H. influenzae meningitis for Sao Paulo state remained below 1 case per
      million population during 2000-2008, although annual incidence of NTHi meningitis
      (mean, 0.03 cases per 100,000 population) increased in several age groups.
      Changes in surveillance for H. influenzae following introduction of Hib conjugate
      vaccine likely contributed to increased numbers of non-b and nontypeable H.
      influenzae meningitis isolates received at the national reference laboratory.

PMID- 21945961
TI  - The clinical benefit and cost-effectiveness of human papillomavirus vaccination
      for adult women in the Netherlands.
AB  - BACKGROUND: The use of human papillomavirus (HPV) vaccines has been universally
      approved for women from age 12 to 25 years, but those older than 16 years receive
      no reimbursement for the cost of the vaccine in the Netherlands. Reductions in
      the vaccine price as well as new insights in the efficacy of HPV vaccines offer
      renewed arguments to consider HPV vaccination in adult women. We calculated the
      clinical benefit and cost-effectiveness of vaccinating women aged 17-25 years in
      2010. METHODS: The calculations were based on an individual-based simulation
      model for cervical carcinogenesis, with HPV infection risks obtained from a type
      specific HPV transmission model. The indirect protective effect from vaccinating
      12 to 16 year-old girls was adjusted for. Cervical screening in the model was
      incorporated according Dutch screening guidelines, i.e. 7 cytology-based rounds
      at 5-year intervals from the age of 30. As base-case, we assumed the vaccine to
      offer full protection against HPV16/18 only if no prior exposure to that type had
      occurred before vaccination. In sensitivity analyses, we considered partial cross
      protection against types 31/33/45/58 and efficacy against all future infections,
      irrespective of previous or current infection status. RESULTS: In base-case
      analyses, vaccinating 17 year-olds reduced their lifetime risk of treatment for
      precancerous lesions from 7.77% to 3.48% and their lifetime cervical cancer risk
      from 0.52% to 0.24%. These risks were 6.12% and 0.45%, respectively, for a 25
      year-old vaccinee. The incremental cost-effectiveness ratio (ICER) for
      vaccinating 17-25 year-olds was ?22,526 per quality-adjusted life-year (QALY) at
      a vaccine price of ?65 per dose, a 50% reduction of the 2010 pharmacy price in
      the Netherlands. If cross-protection against types 31/33/45/58 was included, the
      ICER decreased to ?14,734 per QALY. Results were robust to efficacy assumptions
      with respect to previous or current infection status. CONCLUSION: The clinical
      benefit of HPV vaccination of women up to 25 years moderately depends on cross
      protection to non-vaccine types. Refunding the cost of the vaccine to 17-25 year
      old women in the Netherlands can be considered cost-effective at anticipated
      price reductions.

PMID- 21945962
TI  - Quantitative analysis of neutralizing antibody response to human cytomegalovirus
      in natural infection.
AB  - Naturally acquired immunity significantly reduces the risk of congenital
      cytomegalovirus (CMV) infection in future pregnancies. An immune response
      comparable to that of natural infection has been used as a benchmark for CMV
      vaccine efficacy; however, the magnitude and persistence of the neutralizing
      antibody responses in naturally infected women are not completely understood. In
      this study, we quantitatively analyzed a panel of 375 female CMV convalescent
      sera ranging in age from 18 to 84 years, for its ability to block virus entry
      into epithelial cells and fibroblasts, as well as its binding potential to CMV
      particles. The geometric mean titer of the sera in this panel to neutralize 50%
      of the virus entry into epithelial cells was 7491, compared to 802 for entry into
      fibroblasts. The epithelial neutralizing titers were statistically
      indistinguishable among different age groups, and conformed to a normal
      distribution. There was a weak correlation between the levels of neutralization
      and the binding activities to viral particles. Our data confirmed that natural
      CMV infection in healthy women induces potent neutralizing antibodies against
      infection of both fibroblasts and epithelial cells. The serum neutralizing
      activities were maintained at high levels throughout the child bearing age. The
      corresponding titers may serve as a biomarker for CMV vaccine efficacy.

PMID- 21945963
TI  - Efficient induction of anti-tumor immunity by a TAT-CEA fusion protein vaccine
      with poly(I:C) in a murine colorectal tumor model.
AB  - Protein vaccines may be a useful strategy for cancer immunotherapy because
      recombinant tumor antigen proteins can be produced on a large scale at relatively
      low cost and have been shown to be safe for clinical application. However,
      protein vaccines have historically exhibited poor immunogenicity; thus, an
      improved strategy is needed for successful induction of immune responses. TAT
      peptide is a protein transduction domain composed of an 11-amino acid peptide
      (TAT(47-57): YGRKKRRQRRR). The positive charge of this peptide allows protein
      antigen fused with it to improve cell penetration. Poly(I:C) is a synthetic
      double-stranded RNA that is negatively charged and favors interaction with the
      cationic TAT peptide. Poly(I:C) has been reported on adjuvant role in tumor
      vaccine through promotion of immune responses. Therefore, we demonstrated that
      vaccine with a mixture of TAT-CEA fusion protein and poly(I:C) can induce anti
      tumor immunity in a murine colorectal tumor model. Splenocytes from mice
      vaccinated with a mixture of TAT-CEA fusion protein and poly(I:C) effectively
      induced CEA-specific IFN-gamma-producing T cells and showed cytotoxic activity
      specific for MC-38-cea2 tumor cells expressing CEA. Vaccine with a mixture of TAT
      CEA fusion protein and poly(I:C) delayed tumor growth in MC-38-cea-2 tumor
      bearing mice. Depletion of CD8(+) T cells and NK cells reversed the inhibition of
      tumor growth in an MC-38-cea2-bearing mice, indicating that CD8(+) T cells and NK
      cells are responsible for anti-tumor immunity by vaccine with a mixture of TAT
      CEA fusion protein and poly(I:C). Taken together, these results suggest that
      poly(I:C) could be used as a potent adjuvant to induce the anti-tumor immunity of
      a TAT-CEA fusion protein vaccine in a murine colorectal tumor model.

PMID- 21945964
TI  - Efficacy of live attenuated vaccines against 2009 pandemic H1N1 influenza in
      ferrets.
AB  - The advent of the H1N1 influenza pandemic (pH1N1) in 2009 triggered the rapid
      production of pandemic influenza vaccines, since seasonal influenza vaccines were
      expected and demonstrated not to provide significant cross-protection against the
      newly emerged pandemic virus. To increase vaccine production capacity and further
      evaluate the effectiveness of different candidate pandemic influenza vaccines,
      the World Health Organization stimulated the evaluation of different vaccination
      concepts including the use of live attenuated influenza vaccines (LAIVs).
      Therefore, we have immunized ferrets intranasally with a single dose of pH1N1
      LAIV from different manufacturers. They all induced adequate serum HI antibody
      titers in the ferrets and protected them against intratracheal wild-type pH1N1
      virus challenge: pH1N1 virus replication in the upper respiratory tract and lungs
      was reduced and no disease signs or severe broncho-interstitial pneumonia were
      observed in any of the vaccinated ferrets. These data together with the
      relatively efficient production process emphasize the potential of the LAIV
      concept for pandemic preparedness.

PMID- 21945965
TI  - Estimation of analyte concentration by surface plasmon resonance-based biosensing
      using parameter identification techniques.
AB  - Surface plasmon resonance-based biosensors have been applied to the determination
      of macromolecule concentration. Up to now, the proposed experimental approaches
      have relied either on the generation of a calibration curve that exploits only a
      few data points from each sensorgram or on multiple injections of the unknown
      sample at various flow rates. In this article, we show that prior knowledge of
      the kinetic parameters related to the interaction of the species with a given
      partner could advantageously reduce the number of injections required by both
      aforementioned methods, thereby reducing experimental time while maintaining a
      good level of confidence on the determined concentrations.

PMID- 21945966
TI  - Detection and quantification of alpha-keto-delta-(N(G),N(G)
      dimethylguanidino)valeric acid: a metabolite of asymmetric dimethylarginine.
AB  - Nitric oxide is an ubiquitary cell signaling substance. Its enzymatic production
      rate by nitric oxide synthase is regulated by the concentrations of the substrate
      L-arginine and the competitive inhibitor asymmetric dimethylarginine (ADMA). A
      newly recognized elimination pathway for ADMA is the transamination to alpha-keto
      delta-(N(G),N(G)-dimethylguanidino)valeric acid (DMGV) by the enzyme alanine
      glyoxylate aminotransferase 2 (AGXT2). This pathway has been proven to be
      relevant for nitric oxide regulation, but up to now no method exists for the
      determination of DMGV in biological fluids. We have developed a liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification
      of DMGV. D(6)-DMGV was used as internal standard. Samples were purified online by
      column switching, and separation was achieved on a porous graphitic carbon
      column. The calibration was linear over ranges of 10 to 200 nmol/L for plasma and
      0.1 to 20 MUmol/L for urine. The intra- and interday accuracies and precisions in
      plasma and urine were better than 10%. In plasma samples, DMGV was present in
      concentrations between 19.1 and 77.5 nmol/L. In urine samples, concentrations
      between 0.0114 and 1.03 MUmol/mmol creatinine were found. This method can be used
      as a tool for the scientific investigation of the ADMA conversion to DMGV via the
      enzyme AGXT2.

PMID- 21945968
TI  - Agreement between axillary, tympanic, and mid-forehead body temperature
      measurements in adult emergency department patients.
AB  - OBJECTIVE: To assess the agreement between noncontact infrared thermometer
      (noncontact) with infrared tympanic thermometer (tympanic) and electronic
      axillary thermometer (axillary) in an adult emergency department population.
      MATERIALS AND METHODS: This is a single-center, cross-sectional, prospective
      trial carried out in a Joint Commission accredited private hospital in Turkiye.
      All consecutive patients above 16 years were included in the study. The
      agreements between three methods were analyzed by Bland-Altman analysis with
      MedCalc 11.0.4 statistical software. RESULTS: Body temperatures were measured on
      400 patients (48% were men, mean 35.9+/-17.3 degrees C). Mean noncontact,
      tympanic, and axillary measurements (+/-SD) were 37.22+/-1.03, 36.72+/-0.95, and
      36.91+/-0.96 degrees C, respectively, whereas Intraclass Correlation Coefficient
      of all measurements was 0.892 (95% confidence interval 0.821-0.929). Binary
      comparisons between body temperature measurements produced mean differences Delta
      axillary-tympanic, Delta axillary-noncontact, and Delta tympanic-noncontact as
      0.5+/-0.63, 0.2+/-0.71, and 0.31+/-0.61 degrees C, respectively. However, the
      agreement limits for axillary and noncontact was between -1.2 and 1.6 degrees C; 
      1.74 and 0.74 degrees C for tympanic and noncontact, and -1.52 and 0.9 degrees C
      for tympanic and noncontact. CONCLUSION: There is a lack of agreement between
      body temperature measurements by noncontact, tympanic, and axillary in the adult
      emergency department population. The easy application may lead noncontact to be
      the preferable method for healthcare providers but large agreement limits should
      be considered.

PMID- 21945967
TI  - Three-dimensional motion aftereffects reveal distinct direction-selective
      mechanisms for binocular processing of motion through depth.
AB  - Motion aftereffects are historically considered evidence for neuronal populations
      tuned to specific directions of motion. Despite a wealth of motion aftereffect
      studies investigating 2D (frontoparallel) motion mechanisms, there is a
      remarkable dearth of psychophysical evidence for neuronal populations selective
      for the direction of motion through depth (i.e., tuned to 3D motion). We compared
      the effects of prolonged viewing of unidirectional motion under dichoptic and
      monocular conditions and found large 3D motion aftereffects that could not be
      explained by simple inheritance of 2D monocular aftereffects. These results (1)
      demonstrate the existence of neurons tuned to 3D motion as distinct from
      monocular 2D mechanisms, (2) show that distinct 3D direction selectivity arises
      from both interocular velocity differences and changing disparities over time,
      and (3) provide a straightforward psychophysical tool for further probing 3D
      motion mechanisms.

PMID- 21945969
TI  - Pitfalls in differential diagnosis of the limping child.

PMID- 21945970
TI  - Extreme hypothermia associated with profound metabolic disturbances.

PMID- 21945971
TI  - Health characteristics associated with gaining and losing private and public
      health insurance: a national study.
AB  - BACKGROUND: Millions of Americans lack or lose health insurance annually, yet how
      health characteristics predict insurance acquisition and loss remains unclear.
      OBJECTIVE: To examine associations of health characteristics with acquisition and
      loss of private and public health insurance. RESEARCH DESIGN AND PARTICIPANTS:
      Prospective observational analysis of 2000 to 2007 Medical Expenditure Panel
      Survey data for persons aged 18 to 63 on entry, enrolled for 2 years. We modeled
      year 2 private and public insurance gain and loss. MEASURES:  DEPENDENT
      VARIABLES: year 2 insurance status [none (reference), any private insurance, or
      public insurance] among those uninsured in year 1 (N=13,022), and retaining or
      losing coverage in year 2 among those privately or publicly insured in year 1
      (N=47,239). INDEPENDENT VARIABLES: age, sex, race/ethnicity, education, income,
      region, urbanity, health status, health conditions, year 1 health expenditures,
      year 1 and 2 employment status, and (in secondary analyses) skepticism toward
      medical care and insurance. RESULTS: In adjusted analyses, lower income and
      education were associated with not gaining and with losing private insurance.
      Poorer health status was associated with public insurance gain. Smoking and being
      overweight were associated with not gaining private insurance, and smoking with
      losing private coverage. Secondary analyses adjusting for medical skepticism
      yielded similar findings. CONCLUSIONS: Social disadvantage and poorer health
      status are associated with gaining public insurance, whereas social advantage,
      not smoking, and not being overweight are associated with gaining private
      insurance, even when adjusting for attitudes toward medical care. Private
      insurers seem to benefit from relatively low health risk selection.

PMID- 21945972
TI  - Comparing VA and private sector healthcare costs for end-stage renal disease.
AB  - BACKGROUND: Healthcare for end-stage renal disease (ESRD) is intensive,
      expensive, and provided in both the public and private sector. Using a societal
      perspective, we examined healthcare costs and health outcomes for Department of
      Veterans Affairs (VA) ESRD patients comparing those who received hemodialysis
      care at VA versus private sector facilities. METHODS: Dialysis patients were
      recruited from 8 VA medical centers from 2001 through 2003 and followed for 12
      months in a prospective cohort study. Patient demographics, clinical
      characteristics, quality of life, healthcare use, and cost data were collected.
      Healthcare data included utilization (VA), claims (Medicare), and patient self
      report. Costs included VA calculated costs, Medicare dialysis facility reports
      and reimbursement rates, and patient self-report. Multivariable regression was
      used to compare costs between patients receiving dialysis at VA versus private
      sector facilities. RESULTS: The cohort comprised 334 patients: 170 patients in
      the VA dialysis group and 164 patients in the private sector group. The VA
      dialysis group had more comorbidities at baseline, outpatient and emergency
      visits, prescriptions, and longer hospital stays; they also had more conservative
      anemia management and lower baseline urea reduction ratio (67% vs. 72%; P<0.001),
      although levels were consistent with guidelines (Kt/V>=1.2). In adjusted
      analysis, the VA dialysis group had $36,431 higher costs than those in the
      private sector dialysis group (P<0.001). CONCLUSIONS: Continued research
      addressing costs and effectiveness of care across public and private sector
      settings is critical in informing health policy options for patients with complex
      chronic illnesses such as ESRD.

PMID- 21945973
TI  - Predicting healthcare utilization using a pharmacy-based metric with the WHO's
      Anatomic Therapeutic Chemical algorithm.
AB  - BACKGROUND: Automated pharmacy claim data have been used for risk adjustment on
      health care utilization. However, most published pharmacy-based morbidity
      measures incorporate a coding algorithm that requires the medication data to be
      coded using the US National Drug Codes or the American Hospital Formulary Service
      drug codes, making studies conducted outside the US operationally cumbersome.
      OBJECTIVE: This study aimed to verify that the pharmacy-based metric with the
      World Health Organization (WHO) Anatomical Therapeutic Chemical (ATC) algorithm
      can be used to explain the variations in health care utilization. RESEARCH
      DESIGN: The Longitudinal Health Insurance Database of Taiwan's National Health
      Insurance enrollees was used in this study. We chose 2006 as the baseline year to
      predict the total cost, medication cost, and the number of outpatient visits in
      2007. The pharmacy-based metric with 32 classes of chronic conditions was
      modified from a revised version of the Chronic Disease Score. RESULTS: The
      ordinary least squares (OLS) model and log-transformed OLS model adjusted for the
      pharmacy-based metric had a better R in concurrently predicting total cost
      compared with the model adjusted for Deyo's Charlson Comorbidity Index and
      Elixhauser's Index. The pharmacy-based metric models also provided a superior
      performance in predicting medication cost and number of outpatient visits. For
      prospectively predicting health care utilization, the pharmacy-based metric
      models also performed better than the models adjusted by the diagnosis-based
      indices. CONCLUSIONS: The pharmacy-based metric with the WHO ATC algorithm and
      the matching ATC codes were tested and found to be valid for explaining the
      variation in health care utilization.

PMID- 21945974
TI  - Gender differences in multiple underlying dimensions of health-related quality of
      life are associated with sociodemographic and socioeconomic status.
AB  - PURPOSE: The purpose of the study was to examine whether gender differences in
      summary health-related quality of life (HRQoL) are due to differences in specific
      dimensions of health, and whether they are explained by sociodemographic and
      socioeconomic (SES) variation. METHODS: The National Health Measurement Study
      collected cross-sectional data on a national sample of 3648 black and white
      noninstitutionalized adults ages 35 to 89 years. Data included the Short Form 36
      Item survey, which yielded separate Mental and Physical Component Summary scores
      (MCS and PCS, respectively), and five HRQoL indexes: Short Form 6 dimension,
      EuroQol 5 dimension, the Health Utilities Indexes Mark 2 and 3, and the Quality
      of Well-Being Scale Self-Administered form. Structural equation models were used
      to explore gender differences in physical, psychosocial, and pain latent
      dimensions of the 5 indexes, adjusting for sociodemographic and SES indicators.
      Observed MCS and PCS scores were examined in regression models to judge
      robustness of latent results. RESULTS: Men had better estimated physical and
      psychosocial health and less pain than women with similar trends on the MCS and
      PCS scores. Adjustments for marital status or income reduced gender differences
      more than did other indicators. Adjusting results for partial factorial
      invariance of HRQoL attributes supported the presence of gender differentials,
      but also indicated that these differences are impacted by dimensions being
      related to some HRQoL attributes differently by gender. CONCLUSIONS: Men have
      better estimated health on 3 latent dimensions of HRQoL-physical, psychosocial,
      and pain-comparable to gender differences on the observed MCS and PCS scores.
      Gender differences are partly explained by sociodemographic and SES factors,
      highlighting the role of socioeconomic inequalities in perpetuating gender
      differences in health outcomes across multiple domains. These results also
      emphasize the importance of accounting for measurement invariance for meaningful
      comparison of group differences in estimated means of self-reported measures of
      health.

PMID- 21945975
TI  - Improving risk equalization using multiple-year high cost as a health indicator.
AB  - BACKGROUND: More and more competitive health insurance markets use risk
      equalization to compensate health plans for the predictable high costs of
      chronically ill enrollees. In the presence of premium rate restrictions, an
      important goal of risk equalization is to reduce incentives for selection, while
      maintaining incentives for efficiency. The literature shows, however, that even
      the most sophisticated risk equalization models--which include both diagnoses
      based and pharmacy-based indicators of health status--do not reduce incentives
      for selection sufficiently. OBJECTIVES: The goal of this study is to examine the
      extent to which a sophisticated risk-equalization model can be improved by using
      multiple-year high cost as a health indicator. The idea is that health plans
      receive an additional compensation for enrollees whose costs were in the top-15%
      in each of the 3 preceding years, assuming that this group contains a substantial
      overrepresentation of people with a chronic condition. RESEARCH DESIGN: We
      examine 3 types of additional compensation: (1) retrospective compensation, (2)
      fixed prospective compensation, and (3) continuous prospective compensation.
      SUBJECTS: We use individual-level information on medical costs and risk
      characteristics from the period 2004 to 2007 for almost the entire Dutch
      population. MEASURES: The effect on selection incentives is measured by
      predictive ratios for subgroups of enrollees who were undercompensated in
      previous years. The effect on efficiency incentives is quantified by the
      relationship between cost and compensation. RESULTS AND CONCLUSIONS: All 3
      modalities substantially reduce incentives for selection, but--to some extent-
      also reduce incentives for efficiency. With respect to these criteria, the
      continuous prospective compensation outperforms the other 2 modalities.

PMID- 21945976
TI  - How dangerous is a day in hospital? A model of adverse events and length of stay
      for medical inpatients.
AB  - BACKGROUND: Despite extensive research into adverse events, there is no
      quantitative estimate for the risk of experiencing adverse events per day spent
      in hospital. This is important information for hospital managers, because they
      may consider discharging patients earlier to alternative care providers if this
      is associated with lower risk, but other costs and benefits are similar. METHODS:
      We model adverse events as a function of patient risk factors, hospital fixed
      effects, and length of stay. Potential endogeneity of length of stay is addressed
      with instrumental variable methods, using days and months of discharge as
      instruments. We use administrative hospital episode data for 206,489 medical
      inpatients in all public hospitals in the state of Victoria, Australia, for the
      year 2005/2006. RESULTS: A hospital stay carries a 5.5% risk of an adverse drug
      reaction, 17.6% risk of infection, and 3.1% risk of ulcer for an average episode,
      and each additional night in hospital increases the risk by 0.5% for adverse drug
      reactions, 1.6% for infections, and 0.5% for ulcers. Length of stay is endogenous
      in models of adverse events, and risks would be underestimated if length of stay
      was treated as exogenous. CONCLUSIONS: The results of our research contribute to
      assessing the benefits and costs of hospital stays-and their alternatives-in a
      quantitative manner. Instead of discharging patients early to alternative care,
      it would be more desirable to address underlying causes of adverse events.
      However, this may prove costly, difficult, or impossible, at least in the short
      run. In such situations, our research supports hospital managers in making
      informed treatment and discharge decisions.

PMID- 21945977
TI  - Physician-patient language concordance and malpractice concerns.
AB  - OBJECTIVE: To study the association between physician-patient language
      concordance and physicians' malpractice concerns. METHOD: We use a nationally
      representative physician data set, the 2008 Health Tracking Physician Survey
      maintained by the Center for Studying Health System Change. The Health Tracking
      Physician Survey includes 5 assessments of physicians' concerns about malpractice
      risk. Physicians are also asked the percentage of patients they have difficulty
      in understanding owing to language barriers. We estimate multivariate logistic
      regressions to investigate the association between physician-patient language
      concordance and physicians' malpractice concerns. RESULTS: Physicians who have
      difficulty understanding patients owing to language barriers are 27% to 74% more
      likely to order extra tests or ask for consultant opinions to avoid the risk of
      malpractice suits. They are also 30% to 90% more likely to worry or feel pressure
      about malpractice risk, compared with those without difficulty understanding
      patients owing to language barriers. CONCLUSIONS: It is important to understand
      the incentives associated with malpractice concerns to move physicians toward
      cost-effective healthcare delivery. Our results show that physicians having
      difficulty understanding patients owing to language barriers are more likely to
      have malpractice concerns. Understanding this association may have important
      implications for reducing physicians' malpractice concerns.

PMID- 21945978
TI  - Effects of nurse staffing and nurse education on patient deaths in hospitals with
      different nurse work environments.
AB  - CONTEXT: Better hospital nurse staffing, more educated nurses, and improved nurse
      work environments have been shown to be associated with lower hospital mortality.
      Little is known about whether and under what conditions each type of investment
      works better to improve outcomes. OBJECTIVE: To determine the conditions under
      which the impact of hospital nurse staffing, nurse education, and work
      environment are associated with patient outcomes. DESIGN, SETTING, AND
      PARTICIPANTS: Outcomes of 665 hospitals in 4 large states were studied through
      linked data from hospital discharge abstracts for 1,262,120 general, orthopedic,
      and vascular surgery patients, a random sample of 39,038 hospital staff nurses,
      and American Hospital Association data. MAIN OUTCOME MEASURES: A 30-day inpatient
      mortality and failure-to-rescue. RESULTS: The effect of decreasing workloads by 1
      patient/nurse on deaths and failure-to-rescue is virtually nil in hospitals with
      poor work environments, but decreases the odds on both deaths and failures in
      hospitals with average environments by 4%, and in hospitals with the best
      environments by 9% and 10%, respectively. The effect of 10% more Bachelors of
      Science in Nursing Degree nurses decreases the odds on both outcomes in all
      hospitals, regardless of their work environment, by roughly 4%. CONCLUSIONS:
      Although the positive effect of increasing percentages of Bachelors of Science in
      Nursing Degree nurses is consistent across all hospitals, lowering the patient-to
      nurse ratios markedly improves patient outcomes in hospitals with good work
      environments, slightly improves them in hospitals with average environments, and
      has no effect in hospitals with poor environments.

PMID- 21945980
TI  - A school-based, peer leadership physical activity intervention for 6th graders:
      feasibility and results of a pilot study.
AB  - BACKGROUND: The aim of this study was to promote physical activity in 6th graders
      by developing and testing the feasibility of an enhanced Presidential Active
      Lifestyle Award (PALA) program comprised of a peer leadership component and
      innovative exercise resource toolkit including DVDs. METHODS: A
      racially/ethnically diverse sample of students received the standard PALA program
      (2 control schools, n = 61) or enhanced PALA+Peers program (2 intervention
      schools, n = 87) during 2006-2007 academic year. RESULTS: Compared with the
      control condition, the intervention was successful in increasing moderate
      physical activity in all students (P = .02) and moderate and hard physical
      activity among girls (P = .03 and P = .04, respectively). Teachers and students
      reported a high level of satisfaction and receptivity with the intervention. All
      teachers thought the DVDs were well-received, and 87% of students reported that
      they would recommend the enhanced program to peers. CONCLUSION: Coupling peer
      leadership and DVDs that promote physical activity may be an effective way to
      increase youth physical activity.

PMID- 21945981
TI  - Dietary flavanols exert different effects on antioxidant defenses and
      apoptosis/proliferation in Caco-2 and SW480 colon cancer cells.
AB  - Flavanols intake has been associated with reduced risk of cancer. In this study,
      the anticarcinogenic effects of the flavanols epicatechin (EC), epicatechin
      gallate (ECG) and procyanidin B2 (PB2) on Caco-2 and SW480 colon cancer cells
      were investigated. Catechins showed different cytotoxicity depending on the cell
      line. ECG displayed strong growth inhibitory effects against SW480 cells, but was
      ineffective on Caco-2 cells. In contrast, PB2 did not affect Caco-2 cells,
      whereas promoted cell growth in SW480 cells and EC had no obvious effects on any
      cell line. Exposure of SW480 cells to ECG led to apoptosis as determined by
      caspase-3 activity, imbalance among Bcl-2 anti- and pro-apoptotic protein levels,
      ERK activation and AKT inhibition, whereas PB2 treatment enhanced phospho-AKT and
      phospho-ERK levels. Incubation of Caco-2 cells with ECG increased glutathione
      levels without affecting the expression of pro- and anti-apoptotic Bcl-2
      proteins, AKT or ERK. The results suggest that the different cytotoxicity of
      flavanols is caused by their different activity and the degree of differentiation
      of the colon cancer cell line. Thus, ECG induced apoptosis in SW480 cells and
      contributed to the cytotoxic effect, whereas ECG enhanced the antioxidant
      potential in Caco-2 cells. PB2 activated cell proliferation and
      survival/proliferation pathways in SW480 cells.

PMID- 21945982
TI  - Neuropsychological assessment:  a valuable tool in the diagnosis and management
      of neurological, neurodevelopmental, medical, and psychiatric disorders.
AB  - For both children and adults with neurological, neurodevelopmental, medical, or
      psychiatric disorders, neuropsychological assessment can be a valuable tool in
      determining diagnosis, prognosis, and functional abilities as well as informing
      clinical management. This review summarizes the contributions of
      neuropsychological assessment to clinical care across diagnostic categories, with
      the goal of helping clinicians determine its utility for individual patients.

PMID- 21945983
TI  - Ideational apraxia in Parkinson disease.
AB  - OBJECTIVE: : The objective of the study was to determine whether ideational
      apraxia (IA), a loss of ability to plan the sequence of actions needed to achieve
      a goal, is associated with Parkinson disease (PD). BACKGROUND: : The frontal
      lobes play an important role in planning and sequencing, and many patients with
      PD have frontal lobe dysfunction. METHODS: : Ten right-handed patients with PD
      and 10 right-handed neurologically and psychiatrically healthy people
      participated. To assess for IA, participants were given sets of pictures that
      showed the steps in completing a task, but the steps were shown out of order. The
      participants were required to point to the pictures in the correct sequence to
      complete each task. The participants also performed a control task of sequencing
      randomly arranged printed single words to create a sentence that described an
      accompanying picture. RESULTS: : The patients with PD performed more poorly than
      the controls on the action-sequencing tasks (P<0.05). Errors were predominantly
      in sequencing rather than repetition or omission, indicating that the poor
      performance was not caused by perseveration. There were no group differences in
      the task of sequencing words to make a sentence. CONCLUSIONS: : These results
      indicate that patients with PD do have IA, an action-sequence planning deficit.
      Further research is needed to better understand mechanisms, ecological
      implications, and potential treatments.

PMID- 21945984
TI  - APOE epsilon4 is associated with exacerbation of cognitive decline in patients
      with multiple sclerosis.
AB  - BACKGROUND: : In previous studies we and others have demonstrated an association
      with apolipoprotein (APOE) epsilon4 genotype and the presence of cognitive
      deficits in multiple sclerosis (MS). In this follow-up study, we have assessed
      whether APOE epsilon4 status exacerbates progression of cognitive deficits in MS.
      METHODS: : A total of 197 patients with MS were assessed for APOE genotype, and
      baseline cognitive performance was measured using a standardized battery of
      tests. One hundred seventy patients (86.3%) were clinically followed up for 1
      year and were assessed for progression of cognitive deficits. RESULTS: : The APOE
      epsilon4 allele was present in 24.7% of patients. During 1-year follow-up,
      significant progression of cognitive deficits was found in APOE epsilon4 carriers
      (P=0.001) after logistic regression analysis controlling for sex, ethnicity, age,
      education, disease duration, severity, and subtype. CONCLUSIONS: : APOE epsilon4
      carriers with MS have worsening progression of cognitive deficits than
      noncarriers. APOE epsilon4 carrier status predicts cognitive decline in verbal
      learning and memory.

PMID- 21945985
TI  - Is knowledge of famous people compromised in mild cognitive impairment?
AB  - OBJECTIVE: : This study addressed the issue of whether person naming deficits in
      mild cognitive impairment (MCI) occurred with deficits in person semantic
      knowledge and whether person knowledge was more impaired than general semantics.
      BACKGROUND: : Recent definitions of MCI are beginning to encompass cognitive
      impairments outside the domain of episodic memory. Increasing evidence suggests
      that semantic memory may also be compromised in this patient group, including
      tasks of person naming and identification. METHODS: : Thirteen MCI patients and
      14 control subjects matched for age and education performed parallel semantic
      batteries designed to probe person and general semantic knowledge. RESULTS: : On
      the person battery, the MCI patients demonstrated impairment relative to
      controls, on tasks of category fluency, naming, identification, verbal and
      nonverbal associative and sorting tasks, as well as matching names to faces. By
      contrast, on the general semantic battery impairments, they were impaired only on
      category fluency and the nonverbal sorting and associative tasks. A composite
      measure of person knowledge tasks was also sensitive to disease severity as
      measured by Mini-Mental State Examination. CONCLUSIONS: : These results support
      the existence of deficits in MCI across various domains of person knowledge, and
      the suggestion that deterioration of unique semantic exemplars may be sensitive
      to incipient Alzheimer disease.

PMID- 21945986
TI  - Cognitive performance in asymptomatic patients with advanced carotid disease.
AB  - OBJECTIVE: : In the absence of stroke or transient ischemic attack, patients with
      advanced carotid stenosis or occlusion (ICAs/o) are considered asymptomatic, yet
      they are prone to mostly subtle cognitive impairment. BACKGROUND: : The Mini
      Mental State Examination (MMSE) often fails to detect mild cognitive impairment.
      The Montreal Cognitive Assessment (MoCA) is more sensitive in recognizing such
      changes. METHODS: : Scores on the MoCA and MMSE were compared in 70 asymptomatic
      patients with ICAs/o and 70 controls matched for demographic variables and
      vascular risk factors. RESULTS: : MMSE scores fell mostly within the normal range
      in both patients and controls. Differences were significant for total MoCA scores
      (P<0.001). Patients with ICAs/o performed worse on visuospatial and executive
      function (P=0.018), abstraction (P<0.001), and delayed recall (P<0.001). Lower
      MoCA scores were associated with diabetes (odds ratio=6.41; 95% confidence
      interval, 1.277-32.220; P=0.024) and older age (odds ratio=0.86; 95% confidence
      interval, 0.780-0.956; P=0.004). Patients with diabetes performed worse on
      delayed recall (P<0.001), and patients with hypertension were worse on the MoCA
      naming subtest (P=0.04). CONCLUSIONS: : The MoCA successfully identified reduced
      cognitive status in patients with ICAs/o. The MoCA subtest scores revealed a
      pattern of cognitive impairment similar to that documented in other studies using
      more extensive neuropsychological tests. MoCA could be used as part of the
      clinical evaluation of patients with ICAs/o.

PMID- 21945987
TI  - St Theresa's dart and a case of religious ecstatic epilepsy.
AB  - OBJECTIVE: : We report a case of ecstatic seizures with religious overtones in a
      patient whose semiology resembles that of Saint Theresa of Avila (1515 to 1582),
      and review the anatomical basis of this phenomenon. BACKGROUND: : Seizures with
      an emotional component are typically associated with negative sensations.
      Ecstatic seizures, particularly those with a religious character, are rarely
      reported, although they hold an important place in history, as a number of
      religious figures have been posited to be epileptic. Here, we present a patient
      with ecstatic seizures whose semiology and religious overtones resemble those of
      Saint Theresa of Avila (1515 to 1582), and discuss the anatomical basis of this
      phenomenon. METHOD: : Case report. RESULTS: : Evaluation of the patient
      demonstrated right temporal encephalomalacia on magnetic resonance imaging of the
      brain. Electroencephalogram showed focal slowing and poorly defined sharp waves
      in the right frontotemporal region. This area of pathology concurs with prior
      studies that localize ecstatic seizures to the anterior insula or temporal lobes.
      CONCLUSIONS: : Ecstatic seizures may involve the right temporal region. Although
      interpretation of ecstatic seizures is subject to individual variation, a similar
      localization and our patient's religious background may explain the resemblance
      between the semiology of his seizures, and that of Saint Theresa's visions as
      described almost 5 centuries ago.

PMID- 21945988
TI  - "Language construction in an autistic child:  thoughts regarding language
      acquisition and language therapy":  translation, update, and commentary on a 1977
      case report.
AB  - A 1977 Swiss case study is presented in English translation: a mute child with
      infantile autism is taught to speak starting at the relatively late age of 6. The
      author, who is the primary therapist and the child's father, details the
      conditioning procedure, discusses theoretical considerations in speech
      acquisition, and outlines the limits of the training. The author and translator
      update the child's status and add commentary.

PMID- 21945989
TI  - Epigallocatechin-3-gallate induces cytokine production in mast cells by
      stimulating an extracellular superoxide-mediated calcium influx.
AB  - The green tea polyphenol (-)-epigallocatechin-3-O-gallate (EGCG) has various
      biological activities, including anti-inflammatory, anti-neoplastic, anti- and
      pro-apoptotic, and neuroprotective effects. Although these are often associated
      with increased intracellular reactive oxygen species (ROS) and Ca(2+) levels,
      their involvement in biological effects is poorly understood. Here we report that
      EGCG induces cytokine production in mast cells via Ca(2+) influx and ROS
      generation. EGCG at concentrations of >=50 MUM induced interleukin-13 and tumor
      necrosis factor-alpha production in RBL-2H3 and bone marrow-derived mast cells.
      The effects were dependent on extracellular Ca(2+), and EGCG induced Ca(2+)
      release from intracellular stores and Ca(2+) influx. Ca(2+) influx was suppressed
      by 2-aminoethoxydiphenyl borate, an inhibitor of store-operated Ca(2+) (SOC)
      channels, including Ca(2+) release-activated Ca(2+) channels and transient
      receptor potential canonical channels. EGCG failed to induce Ca(2+) influx
      through SOC channels. EGCG-activated Ca(2+) channels were genetically and
      pharmacologically distinct from Ca(v)1.2 L-type Ca(2+) channels, another route of
      Ca(2+) influx into mast cells. EGCG evoked release of superoxide (O(2)(.-)) into
      the extracellular space. Exogenous superoxide dismutase, but not catalase,
      inhibited EGCG-evoked Ca(2+) influx and cytokine production, indicating that
      extracellular O(2)(.-) regulates these events. EGCG can serve as a powerful tool
      for studying O(2)(.-)-regulated Ca(2+) channels, which may be selectively
      involved in the regulation of cytokine production but have yet to be elucidated.

PMID- 21945990
TI  - Basic diagnosis of solid waste generated at Agua Blanca State Park to propose
      waste management strategies.
AB  - State parks are highly sensitive areas of great natural importance and tourism
      value. Herein a case study involving a basic survey of solid waste which was
      carried out in 2006 in Agua Blanca State Park, Macuspana, Tabasco, Mexico with
      two sampling periods representing the high and low tourist season is presented.
      The survey had five objectives: to find out the number of visitors in the
      different seasons, to consider the daily generation of solid waste from tourist
      activities, to determine bulk density, to select and quantify sub-products; and
      to suggest a possible treatment. A daily average of 368 people visited the park:
      18,862 people in 14 days during the high season holiday (in just one day, Easter
      Sunday, up to 4425 visitors) and 2092 visitors in 43 days during the low season.
      The average weight of the generated solid waste was 61.267 kg day(-1) and the
      generated solid waste average per person was 0.155 kg person(-1 ) day(-1). During
      the high season, the average increased to 0.188 kg person(-1 ) day(-1) and during
      the low season, the average decreased to 0.144 kg person(-1 ) day(-1). The bulk
      density average was 75.014 kg m(-3), the maximum value was 92.472 kg m(-3) and
      the minimum was 68.274 kg m(-3). The sub-products comprised 54.52% inorganic
      matter; 32.03% organic matter, 10.60% non-recyclable and 2.85% others. Based on
      these results, waste management strategies such as reuse/recycling, aerobic and
      anaerobic digestion, the construction of a manual landfill and the employment of
      a specialist firm were suggested.

PMID- 21945991
TI  - E-waste management challenges in Iran: presenting some strategies for improvement
      of current conditions.
AB  - E-waste is one of the fastest-growing waste streams in Iran, owing to an increase
      in consumption of electrical and electronic equipment. Nevertheless, as is the
      case in some other countries, E-waste management has not received sufficient
      attention. For the successful implementation of any waste management plan
      (including an E-waste management plan), the availability of sufficient and
      accurate information on the quantities and composition of the waste generated and
      on current management conditions is a fundamental prerequisite. At present, in
      Iran, there is no available and accurate information that describes the
      characteristics and generation rate of E-waste or the actual practice of
      management and handling of the waste. For this initial study, eight electronic
      products were selected for the determination of their E-waste generation rate in
      the country, and two cities, Tehran and Tabriz, were selected for assessment of
      the current condition of E-waste management. The study found that the amount of E
      waste generation in the country for the eight selected electronic items alone was
      115,286, 112,914 and 115,151 metric tons in 2008, 2009 and 2010, respectively. Of
      the types of electronic items included in the study, televisions, with an average
      of 42.42%, and PCs, with an average of 32.66% accounted for the greatest
      proportions of the total mass of E-waste generated during 2008-2010. Currently,
      despite the fact that primary legislation for E-waste management (as part of
      general waste legislation) exists in Iran, this primary legislation has not yet
      been implemented. In practical terms, there is no definite policy or plan for the
      allocation of funds to prepare suitable equipment and facilities for the
      management and recycling of E-waste at the end of the products' useful life.
      Proposed improvements in current conditions are identified, first by considering
      other countries' experiences and then suggesting specific practical policies,
      rules, and regulations that should be established and applied to all levels of E
      waste management. One of the most attractive E-waste management policies is an
      extended producer responsibility (EPR) programme in combination with a training
      programme at different levels of society. An approach consisting of a mandated
      product take back is proposed for implementing EPR in Iran. Meanwhile, the Health
      Ministry and the Environmental Protection Agency should strictly supervise E
      waste collection, storage, and recycling and/or disposal, and the Trade and
      Industry Ministries must have more control over the import and production of
      electronic goods.

PMID- 21945992
TI  - Upgrading of a co-digestion plant by implementation of a hydrolysis stage.
AB  - An existing co-digestion plant needed to be rehabilitated after a 20 year
      operational period. This was planned to be done in sequence by halving the
      digester volume for a period of 1.5 years. The aim of the present study was to
      improve the performance of the halved co-digestion capacity by implementing an
      upstream thermal hydrolysis reactor or an ultrasonic pre-treatment of the
      substrates. The results of the ultrasonic bench-scale batch experiments showed
      that an ultrasonic pre-treatment of the co-substrates 'municipal bio-waste
      suspension and excess activated sludge led to disintegration efficiencies of up
      to 51%. However, treating kitchen-waste and primary sludge in the same manner was
      not promising as the disintegration yields were rather low. The results of the
      hydrolysis bench-scale batch experiments showed that the optimal boundary
      conditions for the hydrolysis reactor were a hydrolysis temperature of about 42 
      degrees C at a retention time of 24 h. The results of the continuous two-stage
      experiments showed that it was possible to reduce the retention time in the
      second stage to about 24% and to increase the biogas yield to about 12.8 %, and
      the methane yield to about 28% as a result of the implementation of the
      hydrolysis reactor in the existing system. After the rehabilitation of the
      existing digesters it was possible to raise the daily substrate input to the two
      existing digesters from 312 to 495 m3 day(-1) with an upstream hydrolysis reactor
      volume of only 474 m3.

PMID- 21945993
TI  - Optimization of nanowire DNA sensor sensitivity using self-consistent simulation.
AB  - In order to facilitate the rational design and the characterization of nanowire
      field-effect sensors, we have developed a model based on self-consistent charge
      transport equations combined with interface conditions for the description of the
      biofunctionalized surface layer at the semiconductor/electrolyte interface.
      Crucial processes at the interface, such as the screening of the partial charges
      of the DNA strands and the influence of the angle of the DNA strands with respect
      to the nanowire, are computed by a Metropolis Monte Carlo algorithm for charged
      molecules at interfaces. In order to investigate the sensing mechanism of the
      device, we have computed the current-voltage characteristics, the electrostatic
      potential and the concentrations of electrons and holes. Very good agreement with
      measurements has been found and optimal device parameters have been identified.
      Our approach provides the capability to study the device sensitivity, which is of
      fundamental importance for reliable sensing.

PMID- 21945994
TI  - Secondary (micro-)saccades: the influence of primary saccade end point and target
      eccentricity on the process of postsaccadic fixation.
AB  - We examine how the size of saccadic under-/overshoot and target eccentricity
      influence the latency, amplitude and orientation of secondary (micro-)saccades.
      In our experiment, a target appeared at an eccentricity of either 6 degrees  or
      14 degrees  of visual angle. Subjects were instructed to direct their gaze as
      quickly as possible to the target and hold fixation at the new location until the
      end of the trial. Typically, increasing saccadic error is associated with faster
      and larger secondary saccades. We show that secondary saccades at distant in
      contrast to close targets have in a specific error range a shorter latency,
      larger amplitude, and follow more often the direction of the primary saccade.
      Finally, we demonstrate that an undershooting primary saccade is followed almost
      exclusively by secondary saccades into the same direction while overshooting
      primary saccades are followed by secondary saccades into both directions. This
      supports the notion that under- and overshooting imply different consequences for
      postsaccadic oculomotor processing. Results are discussed using a model,
      introduced by Rolfs, Kliegl, and Engbert (2008), to account for the generation of
      microsaccades. We argue that the dynamic interplay of target eccentricity and the
      magnitude of the saccadic under-/overshoot can be explained by a different
      strength of activation in the two hemispheres of the saccadic motor map in this
      model.

PMID- 21945995
TI  - Evidence for a subtractive component in motion adaptation.
AB  - Adaptation to a moving stimulus changes the perception of a stationary grating
      and also reduces contrast sensitivity to the adaptor. We determined whether the
      first effect could be predicted from the second. The contrast discrimination (T
      vs. C) function for a drifting 7.5 Hz grating test stimulus was determined when
      observers were adapted to a low contrast (0.075) grating of the same spatial and
      temporal frequency, moving in either the same or the opposite direction as the
      test. The effect of an adaptor moving in the same direction was to move the T vs.
      C function upwards and to the right, in a manner consistent with an increase in
      divisive inhibition. We also measured the effect of adaptation on the motion-null
      point for a counterphasing grating containing two components, one moving in the
      same direction as the adaptor and the other in the opposite direction. Adaptation
      increased the amount of contrast of the adapted component required to achieve the
      motion-null point. However, this shift could not be predicted from the effects of
      adaptation on contrast sensitivity. In particular, the balance point was shifted
      in gratings of high contrast where there was no effect of adaptation on contrast
      discrimination. We suggest that adaptation has a subtractive (recalibration)
      effect in addition to its effects on the contrast transduction function, and that
      this subtractive effect may explain the movement after-effect seen with
      stationary tests.

PMID- 21945996
TI  - Differential PbP27 expression in the yeast and mycelial forms of the
      Paracoccidioides brasiliensis species complex.
AB  - p27 is an antigenic protein produced by Paracoccidioides brasiliensis, the
      etiologic agent of paracoccidioidomycosis (PCM). Despite its unknown function, it
      has been suggested as a putative virulence factor, proposed as a suitable target
      for the design of diagnostic tools and vaccines, and considered as an enhancer in
      antifungal treatment of PCM. We evaluated sequence polymorphisms of PbP27 gene
      sequence among isolates, finding some polymorphisms associated with the isolates'
      phylogenetic origin. In order to determine if there was a differential expression
      pattern between morphological states and among isolates, we also evaluated PbP27
      expression, at transcriptional and translational levels, in mycelia and yeast
      cultures in 14 isolates belonging to the P. brasiliensis species complex (S1,
      PS2, PS3, and "Pb01-like", proposed to be named Paracoccidioides lutzii) by two
      techniques, real time RT-PCR (RT-qPCR) and protein dot blot. For the latter, four
      protein extracts from different cell localizations (SDS or beta-mercaptoethanol,
      cytoplasmic and extracellular proteins) were analyzed for each isolate. p27 was
      present in the four extracts evaluated, mainly in the SDS extract, corresponding
      to an extract containing proteins loosely attached to the cell wall. This
      information correlates with immunohistochemical analysis, where positive staining
      of the yeasts' cell wall was observed. We found that p27 was present in all
      isolates, mainly in the yeast form. This pattern was corroborated by RT-qPCR
      results, with higher expression levels found in the yeast form for most of the
      isolates. The results provide new insights into the expression patterns of this
      protein, and further characterize it in view of potential uses as a diagnostic
      and/or therapeutic tool.

PMID- 21945997
TI  - KSpaceNavigator as a tool for computer-assisted sample tilting in high-resolution
      imaging, tomography and defect analysis.
AB  - This article describes a novel software tool, the KSpaceNavigator, which combines
      sample stage and crystallographic coordinates in a control sphere. It also
      provides simulated kinematic diffraction spot patterns, Kikuchi line patterns and
      a unit cell view in real time, thus allowing intuitive and transparent navigation
      in reciprocal space. By the overlay of experimental data with the simulations and
      some interactive alignment algorithms, zone axis orientations of the sample can
      be accessed quickly and with great ease. The software can be configured to work
      with any double-tilt or tilt-rotation stage and overcomes nonlinearities in
      existing goniometers by lookup tables. A subroutine for matching the polyhedral
      shape of a nanoparticle assists with 3D analysis and modeling. The new
      possibilities are demonstrated with the case of a faceted BaTiO(3) nanoparticle,
      which is tilted into three low-index zone axes using the piezo-controlled TEAM
      stage, and with a multiply twinned tetrahedral Ge precipitate in Al, which is
      tilted into four equivalent zone axes using a conventional double-tilt stage.
      Applications to other experimental scenarios are also outlined.

PMID- 21945998
TI  - Introducing measure-by-wire, the systematic use of systems and control theory in
      transmission electron microscopy.
AB  - Transmission electron microscopes (TEMs) are the tools of choice for academic and
      industrial research at the nano-scale. Due to their increasing use for routine,
      repetitive measurement tasks (e.g., quality control in production lines) there is
      a clear need for a new generation of high-throughput microscopes designed to
      autonomously extract information from specimens (e.g., particle size
      distribution, chemical composition, structural information, etc.). To aid in
      their development, a new engineering perspective on TEM design, based on
      principles from systems and control theory, is proposed here: measure-by-wire
      (not to be confused with remote microscopy). Under this perspective, the TEM
      operator yields the direct control of the microscope's internal processes to a
      hierarchy of feedback controllers and high-level supervisors. These make use of
      dynamical models of the main TEM components together with currently available
      measurement techniques to automate processes such as defocus correction or
      specimen displacement. Measure-by-wire is discussed in depth, and its methodology
      is illustrated through a detailed example: the design of a defocus regulator, a
      type of feedback controller that is akin to existing autofocus procedures.

PMID- 21945999
TI  - Defocus estimation from stroboscopic cryo-electron microscopy data.
AB  - Defocus estimation is an important step for improving the resolution of single
      particle reconstructions. It can be troublesome to estimate the defocus from low
      dose cryo-electron microscopy (cryo-EM) data, particularly if there is not
      sufficient contrast present in the Fourier transform of the micrograph. Most
      existing approaches estimate the defocus from the presence of Thon rings within
      the power spectrum, employing image enhancement techniques to highlight these
      rings. In this paper, an approach to estimating the defocus from a stroboscopic
      image series is described. The image series is used to obtain two statistical
      metrics: figure of merit (FOM) and Q-factor. These metrics have been used to
      estimate the defoci from low-dose stroboscopic cryo-EM data consisting of a
      variable number of images.

PMID- 21946000
TI  - Are electron tweezers possible?
AB  - Positively answering the question in the title, we demonstrate in this work
      single electron beam trapping and steering of 20-300nm solid Al nanoparticles
      generated inside opaque submicron-sized molten Al-Si eutectic alloy spheres.
      Imaging of solid nanoparticles and liquid alloy in real time was performed using
      energy filtering in an analytical transmission electron microscope (TEM). Energy
      filtering TEM combined with valence electron energy-loss spectroscopy enabled us
      to investigate in situ nanoscale transformations of the internal structure,
      temperature dependence of plasmon losses, and local electronic and optical
      properties under melting and crystallization of individual binary alloy
      particles. For particles below 20nm in size, enhanced vibrations of the dynamic
      solid-liquid interface due to instabilities near the critical threshold were
      observed just before melting. The obtained results indicate that focused electron
      beams can act as a tool for manipulation of metal nanoparticles by transferring
      linear and angular mechanical momenta. Such thermally assisted electron tweezers
      can be utilized for touchless manipulation and processing of individual nano
      objects and potentially for fabrication of assembled nanodevices with atomic
      level sensitivity and lateral resolution provided by modern electron optical
      systems. This is by three orders of magnitude better than for light microscopy
      utilized in conventional optical tweezers. New research directions and potential
      applications of trapping and tracking of nano-objects by focused electron beams
      are outlined.

PMID- 21946001
TI  - Coherent Bremsstrahlung effect observed during STEM analysis of dopant
      distribution in silicon devices using large area silicon drift EDX detectors and
      high brightness electron source.
AB  - In this paper, during dopant analysis of silicon devices, we have observed a
      phenomenon generally neglected in EDX analysis: the coherent Bremsstrahlung (CB).
      We discussed the reason why and came to the conclusion that the analytical TEM
      used for these experiments presents a configuration and performances, which makes
      this equipment very sensitive to the CB effect. This is due to large collection
      solid angle and high counting rate of the four silicon drift EDX detectors (SDD),
      a high brightness electron source providing large probe current and moreover a
      geometry favorable to on axis crystal observations. We analyzed silicon devices
      containing Si [110] and Si [100] crystal areas at different energies (80-120
      200keV). We also observed relaxed SiGe (27 and 40at% of Ge). The CB effect, whose
      intensity is maximum near zone axis beam alignment, manifests as characteristic
      broad peaks present in the X-ray spectrum background. The peak energies are
      predicted by a simple formula deduced for the CB models found in the literature
      and that we present simply. We evaluate also the CB peak intensities and discuss
      the importance of this effect on the detection and quantification traces of
      impurities. The CB peaks also give information on the analyzed crystal structure
      (measurement of the periodicity along the zone axis) and allow, in every
      particular experiment or system, to determine the median take off angle of the
      EDX detectors.

PMID- 21946002
TI  - Dynamic reconstruction for atom probe tomography.
AB  - Progress in the reconstruction for atom probe tomography has been limited since
      the first implementation of the protocol proposed by Bas et al. in 1995. This
      approach and those subsequently developed assume that the geometric parameters
      used to build the three-dimensional atom map are constant over the course of an
      analysis. Here, we test this assumption within the analyses of low-alloyed
      materials. By building upon methods recently proposed to measure the tomographic
      reconstruction parameters, we demonstrate that this assumption can introduce
      significant limitations in the accuracy of the analysis. Moreover, we propose a
      strategy to alleviate this problem through the implementation of a new
      reconstruction algorithm that dynamically accommodates variations in the
      tomographic reconstruction parameters.

PMID- 21946003
TI  - Tissue-specific distribution patterns of retinoids and didehydroretinoids in
      rainbow trout Oncorhynchus mykiss.
AB  - Retinoids (vitamin A) are known to be involved in many key biological functions
      in mammals, such as embryonic development, reproduction or vision. Besides
      standard vitamin A forms, freshwater fish tissues contain high levels of
      didehydroretinoids or vitamin A(2) forms. However, the tissue distribution,
      metabolism and function of both standard and particularly the didehydroretinoids
      are still poorly known in fish. In this study, we have quantified the levels of
      retinoids, including retinol, retinaldehyde, retinyl palmitate and their
      corresponding didehydro forms, as well as the levels of the active polar
      retinoids all-trans-, 9-cis- and 13-cis-retinoic acid in distinct tissues of
      juvenile rainbow trout. Our results indicate that the liver is clearly the main
      retinoid storage tissue in juvenile rainbow trout. Didehydroretinoids were
      dominant over retinoids in all analyzed tissues with the exception of plasma.
      Additionally, significant differences among tissues were observed between
      retinoids and didehydroretinoids, such as differences in the ester profiles and
      the proportions between free and esterified forms, suggesting that mechanisms
      that favor the utilization or storage of one of the other groups of compounds
      might exist in fish. Our data also show the presence of polar retinoids in
      different tissues of fish at the fmol/g scale. Overall, this study clearly
      demonstrates the presence of tissue-specific patterns of accumulation of both
      polar and nonpolar retinoids in fish tissues. The biological relevance of these
      findings should be the focus of future studies.

PMID- 21946004
TI  - Development of a web-based survey for monitoring daily health and its application
      in an epidemiological survey.
AB  - BACKGROUND: Early detection of symptoms arising from exposure to pathogens,
      harmful substances, or environmental changes is required for timely intervention.
      The administration of Web-based questionnaires is a potential method for
      collecting information from a sample population. OBJECTIVE: The objective of our
      study was to develop a Web-based daily questionnaire for health (WDQH) for
      symptomatic surveillance. METHODS: We adopted two different survey methods to
      develop the WDQH: an Internet panel survey, which included participants already
      registered with an Internet survey company, and the Tokyo Consumers' Co-operative
      Union (TCCU) Internet survey, in cooperation with the Japanese Consumers' Co
      operative Union, which recruited participants by website advertising. The
      Internet panel survey participants were given a fee every day for providing
      answers, and the survey was repeated twice with modified surveys and collection
      methods: Internet Panel Survey I was conducted every day, and Internet Panel
      Survey II was conducted every 3 days to reduce costs. We examined whether the
      survey remained valid by reporting health conditions on day 1 over a 3-day
      period, and whether the response rate would vary among groups with different
      incentives. In the TCCU survey, participants were given a fee only for initially
      registering, and health information was provided in return for survey completion.
      The WDQH included the demographic details of participants and prompted them to
      answer questions about the presence of various symptoms by email. Health
      information collected by the WDQH was then used for the syndromic surveillance of
      infection. RESULTS: Response rates averaged 47.3% for Internet Panel Survey I,
      42.7% for Internet Panel Survey II, and 40.1% for the TCCU survey. During a
      seasonal influenza epidemic, the WDQH detected a rapid increase in the number of
      participants with fever through the early aberration reporting system.
      CONCLUSIONS: We developed a health observation method based on self-reporting by
      participants via the Internet. We validated the usefulness of the WDQH by its
      practical use in syndromic surveillance.

PMID- 21946006
TI  - No change in progenitor cell proliferation in the hippocampus in Huntington's
      disease.
AB  - Increases in cell proliferation in the hippocampus have been robustly
      demonstrated in animal models of neurodegenerative diseases like Huntington's
      disease (HD). However, in the subventricular zone, animal models of HD have
      demonstrated no change in cell proliferation compared to wild types, while in
      humans there is a distinct increase in cell proliferation in HD cases.
      Interestingly, there have been no reports on cell proliferation in the human
      subgranular zone (SGZ) of the hippocampus in HD, despite numerous transgenic
      mouse models of HD showing decreased proliferation in the SGZ. Furthermore, HD
      can be divided into those with mainly mood and mainly motor symptomatology. We
      hypothesized that HD cases with mainly mood symptomatology would show a greater
      change in hippocampal proliferation, which has previously been implicated in mood
      disorders such as depression. Therefore, in the current study we examined and
      compared proliferation in the SGZ in normal vs. HD, HD mood, and HD motor
      affected cases. However, our results revealed no significant differences in SGZ
      proliferation between normal and HD cases, and no differences when divided into
      groups based on mood and motor symptomatology. Our results were confirmed using a
      range of cell-cycle protein markers and, overall, were comparable with previous
      studies of the human hippocampus, where very little proliferation was detected in
      the adult SGZ. These results demonstrate that in humans the SGZ is far less
      proliferative than the SVZ, and suggests that hippocampal plasticity in humans
      does not primarily involve cell proliferation.

PMID- 21946005
TI  - Truth and consequences of sphingosine-1-phosphate lyase.

PMID- 21946007
TI  - Moving faster while preserving accuracy.
AB  - Achieving movements with accuracy despite the inevitable variability of the
      neuromuscular mechanisms is an important everyday life problem, which has to be
      solved for the production of any adapted motor act, such as walking, writing,
      catching, or pointing. To solve this problem when we have to make goal-directed
      movements as fast as possible, we systematically increase movement time when
      accuracy requirements increase, a ubiquitous phenomenon qualified as speed
      accuracy trade-off. It has been proposed that this speed-accuracy trade-off
      reflects an optimal compromise between speed and accuracy in the presence of
      biological noise and that increasing movement speed inevitably leads to decreased
      motor accuracy. However, the recent finding that muscle cocontraction improves
      movement accuracy may challenge this view and begs the question of how movement
      speed control and cocontraction control coexist. Here, we show that humans are in
      fact able to move faster while preserving movement accuracy, by using a strategy
      where muscles are cocontracted around the joint. As this energetically costly
      cocontraction strategy was not naturally used, this result has two important
      implications. It first demonstrates that a speed modulation strategy is preferred
      to a cocontraction strategy for fast, accurate movements, and it also suggests
      that energy economy prevents us to execute accurate movements as fast as we could
      do. Consequently, we propose that the mechanisms underlying the speed-accuracy
      trade-off are more complex than previously thought, and suggest the existence of
      a previously unknown speed-energy-accuracy trade-off for goal-directed movements.

PMID- 21946008
TI  - Cortical ionotropic glutamate receptor antagonism protects against
      methamphetamine-induced striatal neurotoxicity.
AB  - Binge administration of the psychostimulant drug, methamphetamine (mAMPH),
      produces long-lasting structural and functional abnormalities in the striatum.
      mAMPH binges produce nonexocytotic release of dopamine (DA), and mAMPH-induced
      activation of excitatory afferent inputs to cortex and striatum is evidenced by
      elevated extracellular glutamate (GLU) in both regions. The mAMPH-induced
      increases in DA and GLU neurotransmission are thought to combine to injure
      striatal DA nerve terminals of mAMPH-exposed brains. Systemic pretreatment with
      either competitive or noncompetitive N-methyl-D-aspartic acid (NMDA) antagonists
      protects against mAMPH-induced striatal DA terminal damage, but the locus of
      these antagonists' effects has not been determined. Here, we applied either the
      NMDA receptor antagonist, (dl)-amino-5-phosphonovaleric acid (AP5), or the alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist,
      dinitroquinoxaline-2,3-dione (DNQX), directly to the dura mater over
      frontoparietal cortex to assess their effects on mAMPH-induced cortical and
      striatal immediate-early gene (c-fos) expression. In a separate experiment we
      applied AP5 or DNQX epidurally in the same cortical location of rats during a
      binge regimen of mAMPH and assessed mAMPH-induced striatal dopamine transporter
      (DAT) depletions 1 week later. Our results indicate that both ionotropic
      glutamate receptor antagonists reduced the mAMPH-induced Fos expression in
      cerebral cortex regions near the site of epidural application and reduced Fos
      immunoreactivity in striatal regions innervated by the affected cortical regions.
      Also, epidural application of the same concentration of either antagonist during
      a binge mAMPH regimen blunted the mAMPH-induced striatal DAT depletions with a
      topography similar to its effects on Fos expression. These findings demonstrate
      that mAMPH-induced dopaminergic injury depends upon cortical NMDA and AMPA
      receptor activation and suggest the involvement of the corticostriatal
      projections in mAMPH neurotoxicity.

PMID- 21946009
TI  - Epicatechin inhibits radiation-induced auditory cell death by suppression of
      reactive oxygen species generation.
AB  - Radiation-induced toxicity limits the delivery of high-dose radiation to head and
      neck lesions. The aim of this study was to investigate the effectiveness of
      epicatechin (EC), a minor component of green tea extract, on radiation-induced
      ototoxicity in vitro and in vivo. The effect of EC on radiation-induced
      cytotoxicity was analyzed in the organ of Corti-derived cell lines, HEI-OC1 and
      UB-OC1. The cell viability, apoptosis, reactive oxygen species generation, and
      mitochondrial membrane potential as well as changes in the signal pathway related
      to apoptosis were investigated. Then, the therapeutic effects of hearing
      protection and drug toxicity of EC were explored in a zebrafish and rat model.
      Radiation-induced apoptosis and altered mitochondrial membrane potential in HEI
      OC1 and UB-OC1 were observed. EC inhibited radiation-induced apoptosis and
      intracellular reactive oxygen species generation. EC markedly attenuated the
      radiation-induced embryotoxicity and protected against radiation-induced loss and
      changes of auditory neuromast in the zebrafish. In addition, intratympanic
      administration of EC was protective against radiation-induced hearing loss in the
      rat model, as determined by click-evoked auditory brainstem (P<0.01). EC
      significantly reduced the expression of p-JNK, p-ERK cleaved caspase-3, and
      cleaved PARP compared to their significant increase after radiation treatment.
      The results of this study suggest that EC significantly inhibited radiation
      induced apoptosis in auditory hair cells and may be a safe and effective
      candidate treatment for the prevention of radiation-induced ototoxicity.

PMID- 21946011
TI  - Cardiovascular risk factors cause cortical thinning in cognitively impaired
      patients: relationships among cardiovascular risk factors, white matter
      hyperintensities, and cortical atrophy.
AB  - Cardiovascular risk factors are associated with cognitive impairments. However,
      the effects of cardiovascular risk factors on the topography of cortical thinning
      have not yet been studied in patients with mild cognitive impairment (MCI) or
      dementia. Thus, we aimed to evaluate the topography of cortical thinning related
      to cardiovascular risk factors and the relationships among cardiovascular risk
      factors, white matter hyperintensities (WMH), and cortical atrophy. Participants
      included 226 patients with Alzheimer disease or subcortical vascular dementia and
      135 patients with amnestic MCI or subcortical vascular MCI. We automatically
      measured the volume of WMH and cortical thickness. Hypertension was associated
      with cortical thinning in the frontal and perisylvian regions, and cortical
      thinning related to diabetes mellitus (DM) occurred in the frontal region. In
      path analyses, hypertension accounted for 0.04 of the frontal thinning with the
      mediation of WMH and 0.16 without the mediation of WMH. In case of DM, it
      accounted for 0.02 of the frontal thinning with the mediation of WMH and 0.13
      without the mediation of WMH. Hypertension and DM predominantly affected frontal
      thinning both with and without the mediation of WMH, where the effects without
      the mediation of WMH were greater than those with the mediation of WMH.

PMID- 21946010
TI  - Migration and fate of therapeutic stem cells in different brain disease models.
AB  - Stem cells have a number of properties, which make them excellent candidates for
      the treatment of various neurologic disorders, the most important of which being
      their ability to migrate to and differentiate predictably at sites of pathology
      in the brain. The disease-directed migration and well-characterized
      differentiation patterns of stem cells may eventually provide a powerful tool for
      the treatment of both localized and diffuse disease processes within the human
      brain. A thorough understanding of the molecular mechanisms governing their
      migratory properties and their choice between different differentiation programs
      is essential if these cells are to be used therapeutically in humans. This review
      focuses on summarizing the migration and differentiation of therapeutic neural
      and mesenchymal stem cells in different disease models in the brain and also
      discusses the promise of these cells to eventually treat various forms of
      neurologic disease.

PMID- 21946013
TI  - Anticipatory grief in new family caregivers of persons with mild cognitive
      impairment and dementia.
AB  - Anticipatory grief is the process of experiencing normal phases of bereavement in
      advance of the loss of a significant person. To date, anticipatory grief has been
      examined in family caregivers to individuals who have had Alzheimer disease (AD)
      an average of 3 to 6 years. Whether such grief is manifested early in the disease
      trajectory (at diagnosis) is unknown. Using a cross-sectional design, we examined
      differences in the nature and extent of anticipatory grief between family
      caregivers of persons with a new diagnosis of mild cognitive impairment (MCI,
      n=43) or AD (n=30). We also determined whether anticipatory grief levels were
      associated with caregiver demographics, caregiving burden, depressive symptoms,
      and marital quality. The mean anticipatory grief levels were high in the total
      sample, with AD caregivers endorsing significantly more anticipatory grief than
      MCI caregivers. In general, AD caregivers endorsed difficulty in functioning,
      whereas MCI caregivers focused on themes of "missing the person" they once knew.
      Being a female caregiver, reporting higher levels of objective caregiving burden,
      and higher depression levels each had independent, statistically significant
      relationships with anticipatory grief. Given these findings, family caregivers of
      individuals with mild cognitive deficits or a new AD diagnosis may benefit from
      interventions specifically addressing anticipatory grief.

PMID- 21946012
TI  - Using mental imagery to improve memory in patients with Alzheimer disease:
      trouble generating or remembering the mind's eye?
AB  - This study was conducted to understand whether patients with mild Alzheimer
      disease (AD) could use general or self-referential mental imagery to improve
      their recognition of visually presented words. Experiment 1 showed that, unlike
      healthy controls, patients generally did not benefit from either type of imagery.
      To help determine whether the patients' inability to benefit from mental imagery
      at encoding was due to poor memory or due to an impairment in mental imagery,
      participants performed 4 imagery tasks with varying imagery and cognitive
      demands. Experiment 2 showed that patients successfully performed basic visual
      imagery, but degraded semantic memory, coupled with visuospatial and executive
      functioning deficits, impaired their ability to perform more complex types of
      imagery. Given that patients with AD can perform basic mental imagery, our
      results suggest that episodic memory deficits likely prevent AD patients from
      storing or retrieving general mental images generated during encoding. Overall,
      the results of both experiments suggest that neurocognitive deficits do not allow
      patients with AD to perform complex mental imagery, which may be most beneficial
      to improving memory. However, our data also suggest that intact basic mental
      imagery and rehearsal could possibly be helpful if used in a rehabilitation
      multisession intervention approach.

PMID- 21946014
TI  - Neuropathological profile of mild cognitive impairment from a population
      perspective.
AB  - Whether the neuropathological profile of mild cognitive impairment (MCI) reflects
      an intermediate state between normal aging and dementia is not clear. Identifying
      which phenomena initiate disease and which occur secondary to the
      neuropathological process is important for targeted disease prevention. Current
      definitions of MCI include amnestic (aMCI), nonamnestic (nMCI), and multidomain
      (mMCI) subtypes. In an unbiased population-based cohort of brain donors, we have
      determined how many individuals fulfill these criteria in the period leading up
      to death [n=10 (5 multidomain MCI, 4 amnestic MCI, 1 nonamnestic MCI)]. All MCI
      cases were collapsed into 1 group and we tested whether their pathologic profile,
      including markers of Alzheimer disease (AD) and vascular disease (VD), is
      intermediate to individuals (matched for age, sex, and education) without
      cognitive impairment (n=20) or dementia (n=20). The main findings are of a
      significant linear trend in the odds of neuritic plaques
      (entorhinal/hippocampus), atrophy (hippocampal and cortical), infarcts, and small
      vessel disease (SVD) with increased cognitive impairment. Neuropathologically,
      MCI is complex, with 10% of MCI brains classified as normal, 10% as VD, 10% as
      AD, and 40% as mixed AD/VD, with the remaining showing other pathologies. Rather
      than pure pathologic changes, several different factors seem to contribute to the
      impairment of MCI. In MCI, both AD and non-AD pathology should be considered as
      possible intervention targets.

PMID- 21946016
TI  - Prodromal dementia with lewy bodies manifesting as sertraline-induced
      parkinsonism: a case report.
AB  - OBJECTIVE: To describe a patient with prodromal dementia with Lewy bodies (DLB)
      manifesting as sertraline-induced parkinsonism. DESIGN: Case report. SETTING:
      Tertiary referral center. PATIENT: A 75-year-old man who initially presented with
      anxiety and depression along with mild cognitive impairment, later developed drug
      induced parkinsonism because of sertraline treatment, and eventually showed
      symptoms and signs of probable DLB. INTERVENTIONS: Sertraline treatment for
      depression. MAIN OUTCOME MEASURES: : Clinical examination, magnetic resonance
      imaging, neuropsychologic test, and cardiac I-metaiodobenzylguanidine
      scintigraphy. RESULTS: His parkinsonian symptoms, which became apparent after
      sertraline therapy, improved markedly after the discontinuation of the drug. When
      he started taking sertraline, he had no dementia but had mild cognitive
      impairment. However, he eventually showed most of the symptoms and signs to
      indicate probable DLB. CONCLUSIONS: To our knowledge, there has been no report of
      sertraline-induced or aggravated parkinsonian motor symptoms in DLB patients. Our
      patient had a short period with neither dementia nor parkinsonism during the
      early stage of his illness, and this period might have been regarded as the
      preclinical stage of DLB in the natural course of his illness.

PMID- 21946015
TI  - Total daily activity measured with actigraphy and motor function in community
      dwelling older persons with and without dementia.
AB  - Actigraphic measures of physical activity do not rely on participants' self
      report and may be of particular importance for examining the health benefits of
      physical activity across the full spectrum of older individuals, especially those
      with dementia, a group in which loss of motor function is particularly salient.
      We tested whether actigraphy could be used to examine the relationship between
      total daily physical activity and motor function in community-dwelling older
      persons both with (n = 70) and without (n = 624) clinical dementia. Total daily
      activity was measured using actigraphy for a median of 9 (range: 2-16) days. All
      participants also underwent a structured examination, including 9 muscle strength
      and 9 motor performance measures summarized as a composite measure. In linear
      regression models controlling for age, sex, and education, total daily activity
      was associated with global motor scores (beta = 0.13, SD = 0.01, P < 0.001). This
      association remained significant after adjusting for body composition, cognition,
      depressive symptoms, disability, vascular risk factors, and diseases (beta =
      0.07, SD = 0.01, P < 0.001). The association did not vary by dementia status
      (interaction P = 0.53). In persons without dementia, the association was
      independent of self-reported physical activity. Total daily activity was
      associated with both muscle strength (beta = 0.10, SD = 0.02, P < 0.001) and
      motor performance (beta = 0.16, SD = 0.02, P < 0.001). Actigraphy can be used in
      the community setting to provide objective measures of total daily activity that
      are associated with a broad range of motor performances. These associations did
      not vary by dementia status. Actigraphy may provide a means to more fully
      explicate the nature and course of motor impairment in old age.

PMID- 21946018
TI  - Tumor and inflammation markers in melanoma using tissue microarrays:  a
      validation study.
AB  - The importance of tumor immune response is ever more evident in melanoma
      carcinogenesis. One approach to explore the pathological mechanisms involved in
      such immune responses, and to analyze other tumor prognostic markers in melanoma,
      is to use tissue microarrays (TMAs). However, TMA technology remains to be
      adequately validated in this setting. Protein expression patterns in whole slides
      and TMA sections from 34 melanoma patients were compared for a number of
      inflammation and tumor cell markers using immunohistochemical stains against CD8
      (lymphocytes), CD163 (macrophages), micropthalmia transcription factor, N
      cadherin, melanoma cell-adhesion molecule, and c-kit protein (CD117). Using
      simplified versions of previously published grading systems, the agreement
      between TMA and whole slide sections ranged between 83 and 96%, and between 81
      and 97% for inflammation and tumor cell markers, respectively. We conclude that
      TMA technology combined with simplified grading systems are appropriate for
      analyzing both inflammation and tumor cell markers in melanoma.

PMID- 21946017
TI  - NALP1/NLRP1 genetic variants are associated with Alzheimer disease.
AB  - Alzheimer disease (AD) is a complex neurodegenerative disease. Genetic and
      molecular studies have confirmed that in the human brain, amyloid-beta fibrils
      can induce, through the activation of NALP1 inflammosome, inflammatory and
      apoptotic responses involved in the pathogenesis of AD. Considering that AD
      pathogenesis is multifactorial, we hypothesized that NALP1/NLRP1 could be a
      susceptibility gene involved in the devolvement of the disease. The possible
      association between 9 selected polymorphisms in the NALP1/NLRP1 gene and AD was
      evaluated by comparing their frequency distribution in an Italian cohort of AD
      patients (AD, n = 276) and in a group of Italian sex-matched and age-matched
      healthy controls without dementia (HC, n = 266). Our study, evidences the
      association of 4 nonsynonymous polymorphisms in the NLRP1 gene (rs2137722,
      rs34733791, rs11657747, rs11651595) with AD. The major alleles of all 4 single
      nucleotide polymorphisms and the corresponding homozygote genotypes were more
      frequent in AD patients than in healthy controls, suggesting an association of
      these variants in the predisposition versus the development of the disease. These
      findings seem to support the previously reported role of NALP1 in neuronal
      damage, and provide evidence of an association between single nucleotide
      variations in the NLRP1 gene and AD.

PMID- 21946019
TI  - Insulin resistance in relation to melanoma risk.
AB  - Obesity, deregulation of adipocytokines, and insulin resistance are interrelated
      and have been implicated in carcinogenesis. In search of novel risk factors for
      melanoma, we explored the association of this disease with insulin resistance in
      a small size, case-control study. Homeostasis Model Assessment for Insulin
      Resistance (HOMA-IR), serum leptin, and adiponectin levels were determined in 55
      patients with incident melanoma and 165 age-matched and sex-matched controls.
      Odds ratios were derived after adjusting for skin type, medical history,
      sociodemographic, lifestyle, and anthropometric parameters. Among the controls,
      HOMA-IR correlated positively with BMI (r=0.34; P=0.0001), waist-to-hip ratio
      (r=0.20; P=0.01) and negatively with serum adiponectin (r=-0.21; P=0.006),
      whereas the correlation with leptin was essentially null (r=0.09; P=0.27). The
      mean HOMA-IR was approximately 1.5 times higher in cases than in controls
      (P=0.05). The established positive association of melanoma with skin type was
      evident in multiple logistic regression models and so was the association with
      increasing HOMA-IR quintile (odds ratio for the fifth quintile=3.68; 95%
      confidence intervals 1.15-11.79, P=0.02). The latter persisted after adjustment
      for anthropometric variables and adiponectin but was attenuated when leptin was
      introduced in the model. These findings point to insulin resistance as a
      potentially independent risk factor for melanoma and need to be confirmed by
      future larger studies, ideally allowing the control of the directionality of the
      association.

PMID- 21946021
TI  - The use of acoustic radiation force-based shear stiffness in non-alcoholic fatty
      liver disease.

PMID- 21946020
TI  - Proton-pumping mechanism of cytochrome c oxidase: a kinetic master-equation
      approach.
AB  - Cytochrome c oxidase is an efficient energy transducer that reduces oxygen to
      water and converts the released chemical energy into an electrochemical membrane
      potential. As a true proton pump, cytochrome c oxidase translocates protons
      across the membrane against this potential. Based on a wealth of experiments and
      calculations, an increasingly detailed picture of the reaction intermediates in
      the redox cycle has emerged. However, the fundamental mechanism of proton pumping
      coupled to redox chemistry remains largely unresolved. Here we examine and extend
      a kinetic master-equation approach to gain insight into redox-coupled proton
      pumping in cytochrome c oxidase. Basic principles of the cytochrome c oxidase
      proton pump emerge from an analysis of the simplest kinetic models that retain
      essential elements of the experimentally determined structure, energetics, and
      kinetics, and that satisfy fundamental physical principles. The master-equation
      models allow us to address the question of how pumping can be achieved in a
      system in which all reaction steps are reversible. Whereas proton pumping does
      not require the direct modulation of microscopic reaction barriers, such kinetic
      gating greatly increases the pumping efficiency. Further efficiency gains can be
      achieved by partially decoupling the proton uptake pathway from the active-site
      region. Such a mechanism is consistent with the proposed Glu valve, in which the
      side chain of a key glutamic acid shuttles between the D channel and the active
      site region. We also show that the models predict only small proton leaks even in
      the absence of turnover. The design principles identified here for cytochrome c
      oxidase provide a blueprint for novel biology-inspired fuel cells, and the master
      equation formulation should prove useful also for other molecular machines. .

PMID- 21946022
TI  - Gangliosides and the multiscale modulation of membrane structure.
AB  - Cellular membranes are highly organized structures with multiple and multi
      dimensional levels of order where lipid components are active players. The lipid
      role is especially evident in rafts, where lipid-driven collective interaction
      dictates the local structure of a membrane. However, lipids play as well other
      roles in many aspects of membrane mechanics and function. In this review, we
      would like to re-focus the attention of the readers on the importance of
      gangliosides in organizing the fine structure of cellular membranes, in lateral
      and transverse directions. Important biological events are likely to be affected
      such as the dynamic control of the shape of specialized plasma membrane areas and
      of the intracellular organelles, the in- and outward budding and fusion of
      membrane vesicles, the physical and functional coupling of the outer and the
      inner plasma membrane leaflet, involved in the transduction of signals across the
      membrane.

PMID- 21946023
TI  - Is there a valid app for that? Validity of a free pedometer iPhone application.
AB  - BACKGROUND: This study examined the validity of a selected free pedometer
      application (iPedometer; IP) for the iPhone that could be used to assess physical
      activity. METHODS: Twenty college students (10 men, 10 women; mean age: 21.85 +/-
      1.57 yrs) wore an iPhone at 3 locations (pocket, waist, arm) and a StepWatch 3
      Step Activity Monitor (SW) on their right ankle while walking on a treadmill at 5
      different speeds (54, 67, 80, 94, 107 m.min(-1)). A research assistant counted
      steps with a tally counter (TC). RESULTS: Statistical significance between the
      TC, SW, and IP was found during every condition except IP in the pocket at 107
      m.min(-1) (F(2,38) = .64, P = .54). Correlations involving the IP revealed only 1
      positive correlation (IP on arm at 54 m.min(-1)) for any of the conditions (r =
      .46, P = .05). CONCLUSION: The IP application was not accurate in counting steps
      and recorded significantly lower step counts than the SW and TC. Thus, the free
      pedometer application used is not a valid instrument for monitoring activity
      during treadmill walking.

PMID- 21946024
TI  - Beneficial effects of chlorogenic acid on methotrexate-induced cerebellar
      Purkinje cell damage in rats.
AB  - Several studies have well confirmed the contribution of oxidative stress in the
      pathogenesis of methotrexate (MTX)-induced damage in the various organs. Many
      agents have been tested experimentally to reduce or inhibit the oxidative stress.
      The aim of this study was to determine the possible protective effect of
      chlorogenic acid (CLG) on MTX-induced cerebellar damage in rats. The rats were
      randomly divided into three groups as follows: I: control group; II: MTX group;
      III: CLG+MTX group. In the MTX group; malondialdehyde (MDA) content was found to
      be increased, whereas superoxide dismutase (SOD), catalase (CAT) activities, and
      glutathione (GSH) content were decreased. On the other hand, CLG markedly
      attenuated the elevated MDA content and prevented the deleterious effects of MTX
      on oxidative stress markers. MTX caused severe loss of Purkinje cells and
      apoptotic cell death in the cerebellum. The CLG administration before MTX
      treatment significantly reduced Purkinje cell damage and the expression of
      apoptotic cells. In conclusion, our results demonstrate that chlorogenic acid
      treatment may protect the impairment of oxidative stress and ameliorate MTX
      induced cerebellar damage at biochemical and histological levels.

PMID- 21946025
TI  - Alterations of brain circuits in Down syndrome murine models.
AB  - Trisomy 21, also referred to Down syndrome (DS), is the most common genetic cause
      of mental retardation, affecting 1 each 800-1000 newborn children all over the
      world. DS is a complex disease, determined by an extra copy of human chromosome
      21 that causes an imbalanced gene dose effect. The syntenies that exist between
      mouse chromosomes 10, 16, and 17 and human chromosome 21 offer the opportunity
      for a genotype-phenotype correlation and several mouse models of DS have been
      developed to improve our knowledge about cognitive disabilities and brain
      alterations. We present here the different murine models available up to now and
      we discuss the neural alterations that have been described in these strains. The
      largest amount of studies involved the so called Ts65Dn mouse showing early
      alterations of nitrergic, noradrenergic and cholinergic systems at the level of
      the basal forebrain. Neurogenesis and spine formations are decreased in the
      hippocampus, as well as the whole size of the cerebellum and the number of
      granule cells.

PMID- 21946026
TI  - Physical activity, sedentary lifestyle, and obesity among Indian dental
      professionals.
AB  - BACKGROUND: Regular physical activity is well recognized as an important
      lifestyle behavior for the development and maintenance of individual and
      population health and well-being. This study was conducted to evaluate physical
      activity, sedentary lifestyle, and obesity among Indian dental health
      professionals. METHODS: Global Physical Activity Questionnaire was used to assess
      physical activity among 324 dental health care professionals. Metabolic
      equivalents (MET) were used to express the intensity of physical activities.
      Obesity was recorded corresponding to Body Mass Index. Individuals were
      considered in high risk group to develop obesity if energy expenditure was < 600
      MET min/week. RESULTS: Total physical activity measured in mean MET minutes per
      week was 625.6, 786.3, 296.5, and 296.5 for third year, final year, interns, and
      faculty, respectively (P <= .05). Obesity was observed in 22.4% of third-year
      students, 16.3% of final-year students, 20.4% of interns, and 40.8% of faculty
      members (P <= .001). CONCLUSION: The sedentary lifestyle of dental health care
      professionals is a major threat to the present and future health of the
      professionals by which the entire community could be prone to an epidemic of
      chronic disease.

PMID- 21946028
TI  - An update in endoscopic management of gastric cancer.
AB  - PURPOSE OF REVIEW: Gastric cancer remains a prevalent disease with a 5-year
      mortality rate of less than 25%. This review focuses on the endoscopic detection,
      staging, and management of gastric adenocarcinoma. RECENT FINDINGS: Confocal
      laser endomicroscopy and narrow band imaging have a 77-99.4% sensitivity for
      early cancer detection, a significant improvement when compared with white light
      endoscopy. Proper staging can be accomplished through endoscopic ultrasound and
      multidetector row-computed tomography, with accuracy as high as 90.1%. Endoscopic
      management of early gastric cancer is minimally invasive and can be preferable to
      surgery. In properly selected patients, endoscopic submucosal dissection has been
      found to have 100% 5-year survival. SUMMARY: The recent advances in gastric
      cancer have greatly improved the care we can offer our patients in gastric
      oncology. The emerging technologies will hopefully continue to promote this
      trend.

PMID- 21946027
TI  - The usefulness of high pre-operative levels of serum type I collagen bone markers
      for the prediction of changes in bone mineral density after parathyroidectomy.
AB  - BACKGROUND: Amino-terminal procollagen propeptide of type I collagen (P1NP) and
      cross-linked C-terminal telopeptide of type I collagen (betaCTX) are two of the
      more sensitive bone markers for reflecting and monitoring patients with an
      increased bone turnover as observed in primary hyperparathyroidism (PHPT)
      patients. AIM: The present study was performed to evaluate the trend of type I
      collagen markers one year after parathyroidectomy (PTX) and to examine the
      relationships between serum P1NP and betaCTX levels and bone mineral density
      (BMD) change after PTX in PHPT Spanish patients. MATERIALS AND METHODS: Fifty
      three PHPT patients were enroled and were followed for one year by measuring
      lumbar BMD, lumbar t-score, lumbar z-score, PTH, calcium, phosphorus, P1NP and
      betaCTX. RESULTS: Pre-surgery concentrations of both markers were elevated (P1NP:
      90.71+/-5.03; betaCTX: 1.52+/-0.44). A significant decrease was observed in mean
      post-operative betaCTX and P1NP concentrations (p<0.0001). Levels of BMD, t-score
      and z-score at lumbar spine were relatively low (BMD: 0.75+/-0.16; z-score 
      0.90+/-0.23; t-score -2.51+/-0.32); after PTX a significant increase was observed
      in the levels of these three parameters. P1NP and betaCTX were correlated with
      lumbar BMD change one year after PTX (P1NP: r=0.79, p=0.016; betaCTX: r=0.89,
      p=0.003). CONCLUSIONS: Pre-surgery concentrations of both bone markers were
      elevated and a significant decrease after PTX was found. Serum betaCTX and P1NP
      levels were potently related to lumbar BMD changes over one year after PTX. The
      measurement of betaCTX and P1NP would be useful to predict long-term changes in
      lumbar BMD after PTX.

PMID- 21946029
TI  - Treatment of Helicobacter pylori.
AB  - PURPOSE OF REVIEW: The article will give an overview on reasons for treatment
      failure and tries to show new concepts for Helicobacter pylori treatment. RECENT
      FINDINGS: Several new treatment options or modifications of already established
      regimens have been introduced to overcome treatment failure. Antibiotic
      resistance to H. pylori is the key factor for treatment failure. At the moment,
      standard triple therapy remains the primary choice in regions with proven low
      clarithromycin resistance rates. In areas with high clarithromycin resistance,
      four drug treatment regimens, including quadruple and sequential therapy, have
      proven the best results as first-line regimens. The options for second-line
      treatment regimens are manifold. Second-line treatment regimens need to be
      adapted accurately to local resistance rates. SUMMARY: Treatment of H. pylori
      infection is challenged by a dramatic fall in eradication rates all over the
      world. Newer regimens have been introduced including sequential, quadruple
      therapies and those regimens provide promising results, but the knowledge about
      local resistance rates remains the key to an effective therapy.

PMID- 21946030
TI  - Role of microbiota in postnatal maturation of intestinal T-cell responses.
AB  - PURPOSE OF REVIEW: Taking advantage of their rapid growth and capacity for
      continuous genetic adaptation, prokaryotes have colonized all possible ecological
      environments on earth, including the body surfaces of eukaryotes and their
      gastrointestinal tract. The mammalian gut contains a complex community of 10
      bacteria with a meta-genome containing 1500-fold more genes than the human
      genome. The forces that control the relationships between eukaryotic hosts and
      their intestinal bacterial symbionts have, thus, become a major focus of
      interest. RECENT FINDINGS: Recent data have highlighted how the dialogue between
      mammalian hosts and their microbiota stimulates the postnatal maturation of an
      efficient intestinal barrier that promotes niche colonization by symbiotic
      bacteria and opposes colonization by pathogens. Herein, we review microbiota
      induced T-cell responses and discuss how individual bacteria may shape the
      balance between regulatory and inflammatory responses. We will also show how host
      factors might influence the outcome of gut immune responses and affect the
      structure of the microbiota. SUMMARY: Deciphering host-microbiota reciprocal
      influence may not only help in understanding the recent outburst of intestinal
      inflammatory diseases but also point to strategies able to maintain or restore
      intestinal homeostasis.

PMID- 21946031
TI  - Hopelessness, a potential endophenotpye for suicidal behavior, is influenced by
      TPH2 gene variants.
AB  - OBJECTIVES: Hopelessness is one of the strongest risk factors for suicidal
      behavior but relevant genetic studies are poorly available. Tryptophan
      hydroxylase (TPH) is widely considered to be a good candidate for genetic
      association studies on depression and suicide, however, investigations on these
      complex, multifactorial phenotypes have resulted in conflicting data. We
      hypothesized that hopelessness could be a mediating phenotype between TPH2 gene,
      depression and suicidal behavior. METHODS: Depressive phenotype and suicidal risk
      were investigated of 760 individuals from general population by Zung Self Rating
      Depression Scale (ZDS), Beck's Hopelessness Scale (BHS) and a detailed background
      questionnaire. All participants' DNA samples were genotyped for 7 tag SNPs in
      TPH2 gene. Generalized linear models were performed for single marker association
      studies and p-values were corrected by Bonferroni criteria. In haplotype analyses
      score tests were used and permutated p-values were computed. RESULTS: Four SNPs
      of TPH2 gene showed association with hopelessness but only rs6582078 had a
      significant effect on the BHS scores after Bonferroni's correction; GG
      individuals had significantly higher BHS scores, while GT and TT had intermediate
      and lower BHS scores respectively (p=0.0047). Compared with other genotypes,
      homozygous GG individuals also had almost three times greater estimated suicidal
      risk, as did carriers of the AA genotype of rs6582078 (OR=2.87; p=0.005) and also
      of rs1352250 (OR=2.86; p=0.006). A risk and a protective haplotype of TPH2 gene
      were also identified in association with hopelessness. ZDS scores have not shown
      any association with TPH2 gene. CONCLUSIONS: We found that hopelessness, with its
      allied increased suicidal risk was strongly associated with TPH2 gene variants in
      multiple tests. These findings suggest that TPH2 gene confers risk for suicidal
      behavior while hopelessness can be a potential endophenotype for suicidal
      vulnerability.

PMID- 21946032
TI  - Improved antimicrobial efficacy with nitric oxide releasing nanoparticle
      generated S-nitrosoglutathione.
AB  - Nitric oxide (NO) plays a vital role in mammalian host defense through a variety
      of mechanisms. In particular, NO can oxidize to form reactive nitrogen species or
      interact with protein thiols and metal centers, blocking essential microbial
      processes. S-nitrosoglutathione (GSNO), a potent NO donor formed by the
      interaction of NO with intracellular glutathione (GSH), is a major factor in this
      pathway and is considered one of the strongest naturally occurring nitrosating
      agent. We previously described the broad-spectrum antimicrobial activity of a
      nanoparticulate platform capable of controlled and sustained release of NO (NO
      np). Interestingly, in vivo efficacy of the NO-np surpassed in vitro data
      generated. We hypothesized that the enhanced activity was in part achieved via
      the interaction between the generated NO and available GSH, forming GSNO. In the
      current study, we investigated the efficiency of NO-np to form GSNO in the
      presence of GSH was evaluated, and assessed the antimicrobial activity of the
      formed GSNO against methicillin resistant Staphylococcus aureus (MRSA),
      Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. When GSH was
      combined with NO-np, GSNO was rapidly produced and significant concentrations of
      GSNO were maintained for >24h. The GSNO generated was more effective compared to
      NO-np alone against all bacterial strains examined, with P. aeruginosa being the
      most sensitive and K. pneumoniae the most resistant. We conclude that the
      combination of NO-np with GSH is an effective means of generating GSNO, and
      presents a novel approach to potent antimicrobial therapy.

PMID- 21946034
TI  - The mystery of two red ears: a bilateral simultaneous case.

PMID- 21946033
TI  - Understanding glaucomatous damage: anatomical and functional data from ocular
      hypertensive rodent retinas.
AB  - Glaucoma, the second most common cause of blindness, is characterized by a
      progressive loss of retinal ganglion cells and their axons, with a concomitant
      loss of the visual field. Although the exact pathogenesis of glaucoma is not
      completely understood, a critical risk factor is the elevation, above normal
      values, of the intraocular pressure. Consequently, deciphering the anatomical and
      functional changes occurring in the rodent retina as a result of ocular
      hypertension has potential value, as it may help elucidate the pathology of
      retinal ganglion cell degeneration induced by glaucoma in humans. This paper
      predominantly reviews the cumulative information from our laboratory's previous,
      recent and ongoing studies, and discusses the deleterious anatomical and
      functional effects of ocular hypertension on retinal ganglion cells (RGCs) in
      adult rodents. In adult rats and mice, perilimbar and episcleral vein
      photocauterization induces ocular hypertension, which in turn results in
      devastating damage of the RGC population. In wide triangular sectors,
      preferentially located in the dorsal retina, RGCs lose their retrograde axonal
      transport, first by a functional impairment and after by mechanical causes. This
      axonal damage affects up to 80% of the RGC population, and eventually causes
      their death, with somal and intra-retinal axonal degeneration that resembles that
      observed after optic nerve crush. Importantly, while ocular hypertension affects
      the RGC population, it spares non-RGC neurons located in the ganglion cell layer
      of the retina. In addition, functional and morphological studies show permanent
      alterations of the inner and outer retinal layers, indicating that further to a
      crush-like injury of axon bundles in the optic nerve head there may by additional
      insults to the retina, perhaps of ischemic nature.

PMID- 21946035
TI  - Treatment of idiopathic intracranial hypertension: Is there a place for
      octreotide?

PMID- 21946036
TI  - Synergistic effects of SPR and FRET on the photoluminescence of ZnO nanorod
      heterostructures.
AB  - Solution-grown ZnO nanorods (NRs) were successfully conjugated with CdSe/ZnS
      quantum dots (QDs) and Ag nanoparticles (NPs) to suppress intrinsic defect
      emission and to enhance band-edge emission at the same time. First, high-density
      and high-crystallinity ZnO NRs of diameter 80-90 nm and length 1.2-1.5 MUm were
      grown on glass substrates using a low-temperature seed-assisted solution method.
      The as-synthesized ZnO NRs showed sharp photoluminescence (PL) band-edge emission
      centered at ~377 nm together with broad defect emission in the range of ~450-800
      nm. The ZnO NRs were decorated with CdSe/ZnS QDs and Ag NPs, respectively, by
      sequential drop-coating. The PL of CdSe/ZnS QD||ZnO NR conjugates showed that ZnO
      band-edge emission decreased by 73.8% due to fluorescence resonance energy
      transfer (FRET) and charge separation between ZnO and CdSe/ZnS by type II energy
      band structure formation. On the other hand, Ag NP||CdSe/ZnS QD||ZnO NR
      conjugates showed increased band-edge emission (by 25.8%) and suppressed defect
      emission compared to bare ZnO NRs. A possible energy transfer mechanism to
      explain the improved PL properties of ZnO NRs was proposed based upon the
      combined effects of FRET and surface plasmon resonance (SPR).

PMID- 21946037
TI  - Diagnostic value of leukopenia in young febrile infants.
AB  - We performed a 7-year registry-based retrospective study. We included 1365
      infants younger than 3 months of age with fever without a source; 81 (5.9%) had
      <5000 leukocytes/mm(3). Among the 1021 well-appearing 29- to 90-day-old infants,
      prevalence of serious bacterial infection (SBI) was 13.8% for those with a normal
      white blood cell count, 6.8% for those with leukopenia (odds ratio, 0.45), and
      36.6% for those with leukocytosis (odds ratio, 3.59). None of the 9 well
      appearing febrile neonates with leukopenia developed an SBI. Leukopenia, in well
      appearing young febrile infants, should not be considered as an SBI risk factor.

PMID- 21946038
TI  - Peer relationships of bereaved siblings and comparison classmates after a child's
      death from cancer.
AB  - OBJECTIVES: To compare peer relationships among bereaved siblings and matched
      classmates, and to examine gender, grade level, and time since death as
      moderators. METHODS: Families were recruited from cancer registries at four
      hospitals 3-12 months after a child's death. Measures of social behavior and peer
      acceptance were completed by children in the classrooms of 105 bereaved siblings
      (ages 8-17 years). Teachers also reported on children's social behavior. Three
      classmates were matched for gender, race, and age to each bereaved sibling to
      form a comparison group (n = 311). RESULTS: Teachers reported bereaved siblings
      were more prosocial than comparison classmates. Peers perceived bereaved boys as
      more sensitive-isolated and victimized, while bereaved siblings in elementary
      grades were perceived by peers as less prosocial, more sensitive-isolated, less
      accepted, and as having fewer friends. Peers and teachers viewed bereaved
      siblings in middle/high school grades as higher on leadership-popularity.
      CONCLUSIONS: Bereaved siblings who were male and in elementary grades were more
      vulnerable to social difficulties, while those in middle/high school may exhibit
      some strengths. Ongoing research to inform the development of interventions for
      bereaved siblings is warranted.

PMID- 21946039
TI  - Perception of other people's mental states affects humor in social anxiety.
AB  - BACKGROUND AND OBJECTIVES: The present study examined the relationship between
      social anxiety and the appreciation of specific types of humor. It was expected
      that social anxiety would hinder the enjoyment of jokes particularly if the
      resolution of incongruity involves processing social cues and assessing the
      (false) mental states of others. Fifty-six participants rated three types of
      cartoons and a control condition for comprehensibility and funniness. RESULTS:
      High degrees of social anxiety were associated with less enjoyment of cartoons
      that involved the interpretation of others' mental states (Theory of Mind), but
      not of semantic cartoons or visual puns. Furthermore, high social anxiety was
      related to longer response latencies of the funniness ratings, especially in the
      case of Theory of Mind cartoons. LIMITATIONS: A possible limitation is that the
      present study was conducted in individuals with social anxiety in the non
      clinical range. CONCLUSIONS: The findings suggest that highly socially anxious
      people do not have a general humor processing deficit, but may feel threatened by
      tasks involving the mental states of others. The negative affect evoked by TOM
      humor may hinder the experience of funniness in highly socially anxious
      individuals, and it may also make it more difficult for them to rate their own
      amusement.

PMID- 21946040
TI  - The relationship between contamination cognitions, anxiety, and disgust in two
      ethnic groups.
AB  - BACKGROUND AND OBJECTIVES: Obsessive-compulsive disorder (OCD) is understudied in
      African Americans, thus little is known about factors that might predispose this
      group to obsessive-compulsive anxiety. Prior research has shown that African
      Americans endorse more concerns about contamination, but it is not known how
      these differences relate to variables, such as beliefs or cognitions about
      contamination, the emotion of disgust, and anxiety sensitivity. The current study
      examined Black-White differences in contamination cognitions in a non-clinical
      sample (N = 245). METHODS: European American and African American participants
      completed measures of contamination cognitions, anxiety, OCD, and disgust.
      RESULTS: African Americans exhibited significantly stronger contamination
      cognitions, as measured by the Contamination Concerns Scale. Multiple regression
      analysis showed that contamination concerns were predicted by disgust
      sensitivity, ethnicity/race, and gender. Neither anxiety sensitivity nor
      pathological washing behaviors were significant factors in the model.
      LIMITATIONS: Study should be replicated in additional populations as
      generalizability beyond a college student population is not known. CONCLUSIONS:
      African Americans are no more sensitive to disgust or anxiety than European
      Americans, but nonetheless have greater concerns about the severity of
      contamination surrounding certain items. This may predispose African Americans
      with OCD to symptoms involving contamination.

PMID- 21946041
TI  - Implicit and explicit self-esteem as concurrent predictors of suicidal ideation,
      depressive symptoms, and loneliness.
AB  - The aim of the present study was to examine whether explicit and implicit self
      esteem, the interaction between these two constructs, and their discrepancy are
      associated with depressive symptoms, suicidal ideation, and loneliness.
      Participants were 95 young female adults (M = 21.2 years, SD = 1.88) enrolled in
      higher education. We administered the Name Letter Task to measure implicit self
      esteem, and the Rosenberg self-esteem scale to assess explicit self-esteem. The
      results indicated that explicit but not implicit self-esteem was negatively
      associated with depressive symptoms, suicidal ideation, and loneliness. The
      interaction of implicit and explicit self-esteem was associated with suicidal
      ideation, indicating that participants with high implicit self-esteem combined
      with a low explicit self-esteem showed more suicidal ideation. Furthermore, the
      size of the discrepancy between implicit and explicit self-esteem was positively
      associated with depressive symptoms, suicidal ideation, and loneliness. In
      addition, results showed that the direction of the discrepancy is an important:
      damaged self-esteem (high implicit self-esteem combined with low explicit self
      esteem) was consistently associated with increased levels of depressive symptoms,
      suicidal ideation, and loneliness, while defensive or fragile self-esteem (high
      explicit and low implicit self-esteem) was not. Together, these findings provide
      new insights into the relationship of implicit and explicit self-esteem with
      depressive symptoms, suicidal ideation, and loneliness.

PMID- 21946042
TI  - Optical radiation and the eyes with special emphasis on children.
AB  - The Sun is the most abundant source of optical radiation for the child eye. New
      hand-held visible lasers are a threat to the child eye. Some scientific data
      suggest that near infrared radiation may cause cumulative damage in the ocular
      lens. The child eye usually is exposed to ambient solar radiation, gazing at the
      horizon. Ambient Sun ultraviolet radiation (UVR) exposure to the child is complex
      due to atmospheric scattering and strong dependence on background reflection.
      Solar exposure causes biological damage, only by photochemical mechanisms. UVR
      exposure to a child eye is mainly a threat to the anterior segment of the eye,
      but also age dependently to the retina. Above threshold exposure to UVR, for
      short delay onset of damage, causes a toxic reaction on the surface of the eye,
      snow blindness, and cataract. Sub-threshold daily exposure to UVR over decades is
      associated with several ocular surface pathologies and eye lid cancer. Visible
      radiation is a threat to the retina. A single above threshold exposure, for short
      delay onset of damage to the retina causes immediate photochemical Type II
      retinal damage, Sun blindness. A single exposure of the retina to a very high
      intensity laser beam may cause thermal or thermo-mechanical damage in the retina.
      In environments with high irradiance of optical radiation, the child eye should
      be protected. Legislation and public information is required for avoidance of
      damage from high intensity laser systems. More research is urgently needed to
      exclude the potential hazard of near infrared radiation.

PMID- 21946043
TI  - Exposure to extremely low-frequency magnetic fields and the risk of childhood
      cancer: update of the epidemiological evidence.
AB  - There is an ongoing scientific controversy whether the observed association
      between exposure to residential extremely low-frequency magnetic fields (ELF-MF)
      and the risk of childhood leukaemia observed in epidemiological studies is causal
      or due to methodological shortcomings of those studies. Recent pooled analysis
      confirm results from previous studies, namely an approximately two-fold risk
      increase at ELF-MF exposures >=0.4 MUT, and demonstrate consistency of studies
      across countries, with different design, different methods of exposure
      assessment, and different systems of power transmission and distribution. On the
      other hand, recent pooled analyses for childhood brain tumour show little
      evidence for an association with ELF-MF, also at exposures >=0.4 MUT. Overall,
      the assessment that ELF-MF are a possible carcinogen and may cause childhood
      leukaemia remains valid. Ongoing research activities, mainly experimental and few
      new epidemiological studies, hopefully provide additional insight to bring
      clarity to a research area that has remained inconclusive.

PMID- 21946045
TI  - Adaptation of Acidithiobacillus bacteria to metallurgical wastes and its
      potential environmental risks.
AB  - Metallurgical wastes--oxygen converter sludge, dust from cast iron production,
      lead matte, and slag from recycling of used lead batteries--were treated with
      Acidithiobacillus bacteria. Bacterial activity and adaptability on waste and some
      waste mixtures were investigated. Acidithiobacillus bacteria may easily attack
      oxygen converter sludge, lead matte and slag and affect the mobility of metals.
      Cast iron dust is not a suitable substrate for applied bacteria due to the
      absence of reduced sulfur and reduced iron in its mineralogical composition.
      Nevertheless, the pure culture was able to adapt to the mixture of this waste
      with slag. Disposal of these metallurgical wastes deserves special attention due
      to potential attack by microorganisms and consequent pH changes. According to
      subsequent release of hazardous substances to the environment, this phenomenon
      can lead to evident environmental risks.

PMID- 21946044
TI  - High expression of BMP pathway genes distinguishes a subset of atypical
      teratoid/rhabdoid tumors associated with shorter survival.
AB  - Molecular profiling of tumors has proven to be a valuable tool for identification
      of prognostic and diagnostic subgroups in medulloblastomas, glioblastomas, and
      other cancers. However, the molecular landscape of atypical teratoid/rhabdoid
      tumors (AT/RTs) remains largely unexplored. To address this issue, we used
      microarrays to measure the gene expression profiles of 18 AT/RTs and performed
      unsupervised hierarchical clustering to determine molecularly similar subgroups.
      Four major subgroups (clusters) were identified. These did not conform to sex,
      tumor location, or presence of monosomy 22. Clusters showed distinct gene
      signatures and differences in enriched biological processes, including elevated
      expression of some genes associated with choroid plexus lineage in cluster 4. In
      addition, survival differed significantly by cluster, with shortest survival
      (mean, 4.7 months) in both clusters 3 and 4, compared with clusters 1 and 2
      (mean, 28.1 months). Analysis showed that multiple bone morphogenetic protein
      (BMP) pathway genes were upregulated in the short survival clusters, with BMP4
      showing the most significant upregulation (270-fold). Thus, high expression of
      BMP pathway genes was negatively associated with survival in this dataset. Our
      study indicates that molecular subgroups exist in AT/RTs and that molecular
      profiling of these comparatively rare tumors may be of diagnostic, prognostic,
      and therapeutic value.

PMID- 21946046
TI  - Cardiorespiratory fitness and fatness are associated with health complaints and
      health risk behaviors in youth.
AB  - BACKGROUND: We examined the association of cardiorespiratory fitness and fatness
      with health complaints and health risk behaviors in 691 (323 girls) Spanish
      children aged 6 to 17.9. METHODS: Health complaints and health risk behaviors
      were self-reported using items of the Health Behavior in School-aged Children
      questionnaire. Weight and height were measured and body mass index was computed.
      Cardiorespiratory fitness was measured by the 20-m shuttle-run test, and youth
      categorized as fit/unfit. RESULTS: Unfit youth were more likely to report health
      complaints sometime (OR: 2.556, 95% CI: 1.299-5.031; and OR: 1.997, 95% CI: 1.162
      3.433, respectively) and health risk behaviors such as drinking alcohol sometime
      (OR: 5.142, 95% CI: 1.214-21.783; and OR: 2.413, 95% CI: 1.484-3.923) than their
      fit counterparts. Overweight-obese youth were more likely to report health
      complaints (OR: 1.732, 95% CI: 1.019-2.945; and OR: 1.983, 95% CI: 1.083-3.629,
      respectively). The analysis of the combined influence of fitness and fatness
      revealed that fit youth had lower health complaints index than the fat-unfit and
      unfat-unfit groups (all P < .05). CONCLUSIONS: Low fitness and overweight-obesity
      increased the risk of having health complaints in youth, yet high levels of
      cardiorespiratory fitness might overcome deleterious effects of overweight
      obesity on health complaints.

PMID- 21946047
TI  - Semen alterations and flow-citometry evaluation in patients with male accessory
      gland infections.
AB  - Male accessory gland infections (MAGI) represent a major cause of male
      infertility mainly through the secretory dysfunction of the prostate, seminal
      vesicles, and epididymis. This study was undertaken to evaluate conventional and
      nonconventional sperm parameters in these patients, therefore 150 patients with
      MAGI were selected. Each of them underwent to two sperm analyses and evaluation
      of DNA fragmentation mitochondrial membrane potential (MMP), phosphatidylserine
      (PS) externalization, chromatin compactness, by flow cytometry. Results showed
      that patients with MAGI had a lower sperm progressive motility (11.4 +/- 5.0 vs
      34.0 +/- 7.0%), and percentage of normal forms (9.0 +/- 3.7 vs 33.0 +/- 13.0%)
      compared to controls, instead, these patients showed higher number of seminal
      white blood cells (2.2 +/- 1.0 vs 0.4 +/- 0.6 106/ml). Patients with MAGI showed
      a higher number of spermatozoa with DNA fragmentation compared to controls (8.2
      +/- 3.0 vs 1.0 +/- 1.0%). In addition, they have also a higher percentage of
      spermatozoa with low MMP (28.0 +/- 4.0 vs 2.0 +/- 2.0%). Patients with MAGI,
      showed a higher percentage of spermatozoa with PS externalization (8.0 +/- 4.0 vs
      3.0 +/- 3.0%), an early sign of apoptosis, and lower percentage of viable
      spermatozoa (64.5 +/- 12.0 vs 88.0 +/- 10.0%). An increased percentage of
      spermatozoa with abnormal chromatin compactness (18.0 +/- 4.0 vs 5.0 +/- 3.0%)
      was found in patients with MAGI. In conclusion, patients with MAGI show
      alterations of conventional and biofunctional sperm parameters compared to
      controls. These results suggest to consider the flow cytometry evaluation among
      the diagnostic tools for male infertility.

PMID- 21946048
TI  - A comparison of a postal survey and mixed-mode survey using a questionnaire on
      patients' experiences with breast care.
AB  - BACKGROUND: The Internet is increasingly considered to be an efficient medium for
      assessing the quality of health care seen from the patients' perspective.
      Potential benefits of Internet surveys such as time efficiency, reduced effort,
      and lower costs should be balanced against potential weaknesses such as low
      response rates and accessibility for only a subset of potential participants.
      Combining an Internet questionnaire with a traditional paper follow-up
      questionnaire (mixed-mode survey) can possibly compensate for these weaknesses
      and provide an alternative to a postal survey. OBJECTIVE: To examine whether
      there are differences between a mixed-mode survey and a postal survey in terms of
      respondent characteristics, response rate and time, quality of data, costs, and
      global ratings of health care or health care providers (general practitioner,
      hospital care in the diagnostic phase, surgeon, nurses, radiotherapy,
      chemotherapy, and hospital care in general). METHODS: Differences between the two
      surveys were examined in a sample of breast care patients using the Consumer
      Quality Index Breast Care questionnaire. We selected 800 breast care patients
      from the reimbursement files of Dutch health insurance companies. We asked 400
      patients to fill out the questionnaire online followed by a paper reminder (mixed
      mode survey) and 400 patients, matched by age and gender, received the
      questionnaire by mail only (postal survey). Both groups received three reminders.
      RESULTS: The respondents to the two surveys did not differ in age, gender, level
      of education, or self-reported physical and psychological health (all Ps > .05).
      In the postal survey, the questionnaires were returned 20 days earlier than in
      the mixed-mode survey (median 12 and 32 days, respectively; P < .001), whereas
      the response rate did not differ significantly (256/400, 64.0% versus 242/400,
      60.5%, respectively; P = .30). The costs were lower for the mixed-mode survey (?2
      per questionnaire). Moreover, there were fewer missing items (3.4% versus 4.4%, P
      = .002) and fewer invalid answers (3.2% versus 6.2%, P < .001) in the mixed-mode
      survey than in the postal survey. The answers of the two respondent groups on the
      global ratings did not differ. Within the mixed-mode survey, 52.9% (128/242) of
      the respondents filled out the questionnaire online. Respondents who filled out
      the questionnaire online were significantly younger (P < .001), were more often
      highly educated (P = .002), and reported better psychological health (P = .02)
      than respondents who filled out the paper questionnaire. Respondents to the paper
      questionnaire rated the nurses significantly more positively than respondents to
      the online questionnaire (score 9.2 versus 8.4, respectively; chi21 = 5.6).
      CONCLUSIONS: Mixed-mode surveys are an alternative method to postal surveys that
      yield comparable response rates and groups of respondents, at lower costs.
      Moreover, quality of health care was not rated differently by respondents to the
      mixed-mode or postal survey. Researchers should consider using mixed-mode surveys
      instead of postal surveys, especially when investigating younger or more highly
      educated populations.

PMID- 21946049
TI  - Replication of simulated prebiotic amphiphile vesicles controlled by experimental
      lipid physicochemical properties.
AB  - We present a new embodiment of the graded autocatalysis replication domain (GARD)
      for the growth, replication and evolution of lipid vesicles based on a semi
      empirical foundation using experimentally measured kinetic values of selected
      extant lipid species. Extensive simulations using this formalism elucidated the
      details of the dependence of the replication and properties of the vesicles on
      the physicochemical properties and concentrations of the lipids, both in the
      environment and in the vesicle. As expected, the overall concentration and number
      of amphiphilic components strongly affect average replication time. Furthermore,
      variations in acyl chain length and unsaturation of vesicles also influence
      replication rate, as do the relative concentrations of individual lipid types.
      Understanding of the dependence of replication rates on physicochemical
      parameters opens a new direction in the study of prebiotic vesicles and lays the
      groundwork for future studies involving the competition between lipid vesicles
      for available amphiphilic monomers.

PMID- 21946050
TI  - Further evidence for promoting transdermal estrogens in the management of
      postmenopausal symptoms.

PMID- 21946052
TI  - High resolution melting curve analysis of DNA samples isolated by different DNA
      extraction methods.
AB  - BACKGROUND: High resolution melting is a post-PCR-based method for detecting DNA
      sequence variation by measuring changes in the melting of a DNA duplex. Melting
      of double-stranded DNA molecules is influenced by several factors. We evaluated
      the influence of the DNA isolation method in the melting curve analysis to detect
      genetic variations. METHODS: We isolated DNA from whole blood of 547 subjects by
      two different methods: Maxwell 16 Instrument and DNA FlexiGene Kit. A fragment of
      159 bp was amplified and analyzed by high resolution melting. Those samples that
      showed a different melting curve pattern were sequenced. RESULTS: Of the samples
      extracted with the Maxwell 16 Instrument, 42% showed variation compared with
      0.18% of the samples extracted with DNA FlexiGene Kit. After sequencing, we
      showed that all samples extracted with the Maxwell 16 Instrument were false
      positive except one, which coincided with the only sample that showed variation
      in those extracted with the DNA FlexiGene Kit. CONCLUSION: The method used to
      extract DNA is an important factor to consider in the analysis of melting curves
      obtained by high resolution melting, as it may influence the melting behaviour of
      the samples, giving false positive results in the detection of genetic variants.

PMID- 21946051
TI  - Evaluation of revisited fucosylated alpha-fetoprotein (AFP-L3) with an
      autoanalyzer MUTAS in a clinical laboratory.
AB  - BACKGROUND: We assessed clinical and analytical performances of AFP and
      fucosylated AFP (AFP-L3) assays by a newly developed automated analyzer based on
      liquid-phase binding (micro-total analysis systems, MUTAS). METHODS: A total of
      239 serum samples were obtained from 120 patients with hepatocellular carcinoma
      (HCC) and 119 without HCC. Precision of assays by the MUTAS was evaluated, and
      the correlation between AFP-L3 and AFP levels was analyzed. Receiver operating
      characteristics curve-area under the curve (ROC-AUC) value was calculated to
      measure the diagnostic performance. RESULTS: Imprecision for AFP (ng/ml), AFP-L3
      (ng/ml), and AFP-L3 (%) with 2 levels of QC materials was all within 5%
      coefficient of variation. AFP levels measured by the MUTAS were correlated well
      with those by the UniCel DxI 800 Access (r=0.83). AFP-L3 concentrations in HCC
      patients were higher than those in control group (median 379.2 ng/ml in HCC, 1.0
      ng/ml in non-HCC, P<0.05). AUC of AFP-L3 was 0.91 which was significantly higher
      than that of AFP (0.88 by MUTAS; 0.84 by UniCel DxI 800, P<0.05 for both).
      CONCLUSION: AFP-L3 in HCC was significantly higher than that of control group.
      The MUTAS showed good performances for routine uses in clinical laboratories for
      measuring AFP and AFP-L3.

PMID- 21946053
TI  - Association between prescribing patterns of anti-asthmatic drugs and clinically
      uncontrolled asthma: a cross-sectional study.
AB  - OBJECTIVE: Studies based on prescription data have shown that many asthmatics
      tend to use large quantities of inhaled beta-2-agonists, suggesting poorly
      controlled disease. The aim of the present study was to investigate the
      association between clinically uncontrolled asthma and prescribing patterns of
      anti-asthmatic drugs with a primary focus on short-acting beta-2-agonists (SABA).
      METHODS: In a cross-sectional study 357 subjects, selected by their prescriptions
      of inhaled beta-2-agonists in Odense Pharmaco-Epidemiological Database, underwent
      individual clinical assessment including the Asthma Control Questionnaire (ACQ)
      and spirometry. The associations between uncontrolled asthma (ACQ score >= 1.50)
      and individual anti-asthmatic prescribing were analysed by means of logistic
      regression. RESULTS: Clinically uncontrolled asthma was positively associated
      with SABA use, the association becoming stronger with higher annual quantity of
      SABA use, odds ratio (OR) 11.1 (95% CI 4.4-28.0) for >=400 DDD/year. This trend
      persisted after stratifying for gender, age, and controller treatment. Although
      subjects using >=450 DDD/year were all uncontrolled, there was substantial
      overlap in SABA use between controlled and uncontrolled subjects below this
      limit. We found no effect modification by age and gender. Use of inhaled
      corticosteroids protected against uncontrolled asthma, OR 0.51 (95% CI 0.27
      0.95). CONCLUSION: Asthmatics with a high use of SABA frequently have problems
      with uncontrolled asthma, and users of ICS are protected against uncontrolled
      asthma. The associations we found were, however, to weak too allow firm
      conclusions about asthma control for most individual asthma patients.

PMID- 21946054
TI  - Small lung cancers: improved detection by use of bone suppression imaging-
      comparison with dual-energy subtraction chest radiography.
AB  - PURPOSE: To determine whether use of bone suppression (BS) imaging, used together
      with a standard radiograph, could improve radiologists' performance for detection
      of small lung cancers compared with use of standard chest radiographs alone and
      whether BS imaging would provide accuracy equivalent to that of dual-energy
      subtraction (DES) radiography. MATERIALS AND METHODS: Institutional review board
      approval was obtained. The requirement for informed consent was waived. The study
      was HIPAA compliant. Standard and DES chest radiographs of 50 patients with 55
      confirmed primary nodular cancers (mean diameter, 20 mm) as well as 30 patients
      without cancers were included in the observer study. A new BS imaging processing
      system that can suppress the conspicuity of bones was applied to the standard
      radiographs to create corresponding BS images. Ten observers, including six
      experienced radiologists and four radiology residents, indicated their confidence
      levels regarding the presence or absence of a lung cancer for each lung, first by
      using a standard image, then a BS image, and finally DES soft-tissue and bone
      images. Receiver operating characteristic (ROC) analysis was used to evaluate
      observer performance. RESULTS: The average area under the ROC curve (AUC) for all
      observers was significantly improved from 0.807 to 0.867 with BS imaging and to
      0.916 with DES (both P < .001). The average AUC for the six experienced
      radiologists was significantly improved from 0.846 with standard images to 0.894
      with BS images (P < .001) and from 0.894 to 0.945 with DES images (P = .001).
      CONCLUSION: Use of BS imaging together with a standard radiograph can improve
      radiologists' accuracy for detection of small lung cancers on chest radiographs.
      Further improvements can be achieved by use of DES radiography but with the
      requirement for special equipment and a potential small increase in radiation
      dose.

PMID- 21946055
TI  - Basic life support equipped with automated external defibrillator may not be
      categorized the same as traditional basic life support in meta-analysis.

PMID- 21946056
TI  - Two new polyols and a new phenylpropanoid glycoside from the basidiomycete
      Lactarius deliciosus.
AB  - Two new polyols, 3-hydroxymethyl-2-methylenepentane-1,4-diol and 1
      methylcyclohexane-1,2,4-triol, and a new phenylpropanoid glycoside, eugenyl 4"-O
      acetyl-beta-rutinoside, together with seven known steroids (5-11) were isolated
      from the fruiting bodies of the basidiomycete Lactarius deliciosus. The
      structures of these compounds were elucidated by the analysis of spectroscopic
      data.

PMID- 21946057
TI  - Microbial transformation of ginsenoside-Rg1 by Absidia coerulea and the reversal
      activity of the metabolites towards multi-drug resistant tumor cells.
AB  - Biotransformation of ginsenoside-Rg1 (1) by the fungus Absidia coerulea AS 3.2462
      yielded five metabolites (2-6). On the basis of spectroscopic data analyses, the
      metabolites were identified as ginsenoside-F1 (2), 6alpha,12beta-dihydroxydammar
      3-one-20(S)-O-beta-D-glucopyranoside (3), 3-oxo-20(S)-protopanaxatriol (4), 3-oxo
      7beta-hydroxy-20(S)-protopanaxatriol (5), and 3-oxo-7beta,15alpha-dihydroxy-20(S)
      protopanaxatriol (6), respectively. Among them, 5 and 6 are new compounds. These
      results indicated that Absidia coerulea AS 3.2462 could catalyze the specific C-3
      dehydrogenation of derivatives of ginsenoside-Rg1, as well as hydroxylation at
      the 7beta and 15alpha positions. Metabolites 2, 4 and 5 exhibited moderate
      reversal activity towards A549/taxol MDR tumor cells in vitro.

PMID- 21946058
TI  - Arsenic trioxide inhibits Ewing's sarcoma cell invasiveness by targeting
      p38(MAPK) and c-Jun N-terminal kinase.
AB  - Ewing's sarcoma is the second most frequent primary malignant bone tumor, mainly
      affecting children and young adults. The notorious metastatic capability of this
      tumor aggravates patient mortality and remains a problem to be overcome. We
      investigated the effect of arsenic trioxide (As2O3) on the metastasis capability
      of Ewing's sarcoma cells. We performed 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl
      2H-tetrazolium bromide assays to choose appropriate concentrations of As2O3 for
      the experiments. Migration, invasion, and adhesion assays were performed to
      assess the effect of As2O3 on the metastasis of Ewing's sarcoma.
      Immunofluorescent staining was used to observe cytoskeleton reorganization in
      Ewing's sarcoma cells treated with As2O3. Changes in matrix metalloproteinase-9
      expression and the mitogen-activated protein kinase (MAPK) pathway were
      investigated using western blot. Inhibitors of p38(MAPK) (sb202190) and c-Jun NH2
      terminal kinase (JNK, sp600125) were used in invasion assays to determine the
      effect of p38(MAPK) and JNK. We found that As2O3 may markedly inhibit the
      migration and invasion capacity of Ewing's sarcoma cells with structural
      rearrangements of the actin cytoskeleton. The expressions of matrix
      metalloproteinase-9, phosphor-p38(MAPK), and phosphor-JNK were suppressed by
      As2O3 treatment in a dose-dependent manner. The inhibitors of p38(MAPK)
      (sb202190) and JNK (sp600125) enhanced the inhibition induced by As2O3, which was
      counteracted by anisomycin, an activating agent of p38(MAPK) and JNK. Taken
      together, our results demonstrate that As2O3 can inhibit the metastasis
      capability of RD-ES and A-673 cells and may have new therapeutic value for
      Ewing's sarcoma.

PMID- 21946059
TI  - Promoting physical activity and fruit and vegetable consumption through a
      community-school partnership: the effects of Marathon Kids(r) on low-income
      elementary school children in Texas.
AB  - BACKGROUND: Marathon Kids(r) (MK) is a community and school-based program that
      promotes running, walking, and healthy eating in elementary school children. This
      study assessed the impact of MK on self-reported physical activity (PA), fruit
      and vegetable consumption (FVC), and related psycho-social factors in a sample of
      low-income, 4th- and 5th-grade students in Texas (n = 511). Intervention
      strategies included structured school running time, behavioral tracking,
      celebratory events, and rewards. METHODS: A quasi-experimental design with 5
      intervention (MK) and 3 comparison schools was employed. Students were assessed
      at baseline in the fall and at 3 time points during 2008 to 09. Mixed-effect
      regression methods were used to model pooled means, adjusting for baseline and
      sociodemographic variables. RESULTS: MK students reported a higher mean time of
      running in past 7 days compared with non-MK students (mean = 4.38 vs. 3.83,
      respectively. P = .002), with a standardized effect size of 0.16. Mean times of
      FVC (P = .008), athletic identity self-concept (P < .001), PA outcome
      expectations (P = .007), and PA and FVC self-efficacy (P < .001 and P = .02,
      respectively) were also higher in MK students. Fewer differences in social
      support were observed. CONCLUSION: Findings provide further evidence on the
      importance of community and school partnerships for promoting PA and healthy
      eating in children.

PMID- 21946061
TI  - Molecular ruler of tripeptidylpeptidase II: mechanistic principle of exopeptidase
      selectivity.
AB  - The structure of tripeptidylpeptidase II (TPPII) has shown that it belongs to the
      group of exopeptidases which use a double-Glu motif to convey aminopeptidase
      activity. TPPII has been implicated in vital biological processes. At least one
      of these, antigen processing, requires the involvement of its endopeptidase
      activity. In order to understand the extent and molecular basis of this unusual
      functional promiscuity we have performed a systematic kinetic analysis of wild
      type Drosophila melanogaster TPPII and five point mutants of the double-Glu-motif
      (E312/E343) involving natural substrates. Unlike the known double-Glu motives of
      other exopeptidases, the double-Glu motif of TPPII is distinctly asymmetrical:
      E312 is the crucial determinant of the aminotripeptidolytic ruler mechanism. It
      both blocks the active-site cleft at substrate position P4 and forms a salt
      bridge with the N-terminus of the substrate. In contrast, E343 forms a much
      weaker salt bridge than E312 and it does not have a blocking role. An
      endopeptidase substrate can bind at relatively high affinity if the length of the
      substrate permits binding to several S' sites. However, the lacking alignment of
      the substrate by the double-Glu motif causes the endopeptidolytic K(cat)/K(M) of
      TPPII to be very low.

PMID- 21946062
TI  - DNA intercalator korkormicin A preferentially kills tumor cells expressing wild
      type p53.
AB  - Korkormicin A belongs to a family of nature-produced cyclic depsipeptides. It has
      potent antitumor activity against both leukemia cell P388 and carcinoma cell
      M109. To further explore its potential as a cancer therapeutic, the mechanism of
      its antitumor activity was investigated. We found that korkormicin A can bind to
      DNA through intercalation. It also induces p53 phosphorylation, which leads to
      inhibition of p53 degradation and activation of p53-dependent transcription.
      Furthermore, korkormicin A preferentially induces apoptosis in transformed cells
      retaining wild type p53. As it has been shown that p53 usually induces apoptosis
      in transformed cells, but only growth arrest in untransformed cells, these
      results indicate that korkormicin A is a potential antitumor agent for cancers
      with wild type p53.

PMID- 21946063
TI  - Comprehensive trapping of polyubiquitinated proteins using the UIM peptide of
      ASB2a.
AB  - An alternative splicing variant of E3 ubiquitin ligase ASB2, termed ASB2a, has a
      distinct N-terminal sequence containing a ubiquitin-interacting motif (UIM)
      consensus sequence. Examination of the minimal essential region for binding to
      polyubiquitinated proteins indicated that the UIM consensus sequence (residues 26
      41) alone is not enough, and that amino acids 12-41 from the N-terminus of ASB2a
      is essential for binding. ASB2a(12-41) peptide was chemically synthesized and
      coupled to Sepharose 4B via disulfide bonds. This ASB2a(12-41) peptide-coupled
      affinity resin bound both K48- and K63-linked polyubiquitinated proteins in cell
      lysates and comprehensively captured polyubiquitinated proteins, including
      polyubiquitinated beta-catenin, I-kappaB, and EGF receptor, which were eluted
      with 2-mercaptoethanol under non-denaturing conditions. These results indicate
      that this UIM affinity purification (designated as ubiquitin-trapping) is a
      useful method to discover polyubiquitinated proteins and their associated
      proteins.

PMID- 21946060
TI  - Fetal hypoxia and programming of matrix metalloproteinases.
AB  - Fetal hypoxia adversely affects the brain and heart development, yet the
      mechanisms responsible remain elusive. Recent studies indicate an important role
      of the extracellular matrix in fetal development and tissue remodeling. The
      matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue
      inhibitors of metalloproteinases (TIMPs) have been implicated in a variety of
      physiological and pathological processes in the cardiovascular and central
      nervous systems. This review summarizes current knowledge of the mechanisms by
      which fetal hypoxia induces the imbalance of MMPs, TIMPs and collagen expression
      patterns, resulting in growth restriction and aberrant tissue remodeling in the
      developing heart and brain. Collectively, this information could lead to the
      development of preventive diagnoses and therapeutic strategies in the fetal
      programming of cardiovascular and neurological disorders.

PMID- 21946064
TI  - AtERF71/HRE2 transcription factor mediates osmotic stress response as well as
      hypoxia response in Arabidopsis.
AB  - Various transcription factors are involved in the response to environmental
      stresses in plants. In this study, we characterized AtERF71/HRE2, a member of the
      Arabidopsis AP2/ERF family, as an important regulator of the osmotic and hypoxic
      stress responses in plants. Transcript level of AtERF71/HRE2 was highly increased
      by anoxia, NaCl, mannitol, ABA, and MV treatments. aterf71/hre2 loss-of-function
      mutants displayed higher sensitivity to osmotic stress such as high salt and
      mannitol, accumulating higher levels of ROS under high salt treatment. In
      contrast, AtERF71/HRE2-overexpressing transgenic plants showed tolerance to salt
      and mannitol as well as flooding and MV stresses, exhibiting lower levels of ROS
      under high salt treatment. AtERF71/HRE2 protein was localized in the nucleus, and
      the C-terminal region of AtERF71/HRE2 was required for transcription activation
      activity. Taken together, our results suggest that AtERF71/HRE2 might function as
      a transcription factor involved in the response to osmotic stress as well as
      hypoxia.

PMID- 21946065
TI  - Triclabendazole protects yeast and mammalian cells from oxidative stress:
      identification of a potential neuroprotective compound.
AB  - The Prestwick and NIH chemical libraries were screened for drugs that protect
      baker's yeast from sugar-induced cell death (SICD). SICD is triggered when
      stationary-phase yeast cells are transferred from spent rich medium into water
      with 2% glucose and no other nutrients. The rapid, apoptotic cell death occurs
      because reactive oxygen species (ROS) accumulate. We found that triclabendazole,
      which is used to treat liver flukes in cattle and man, partially protects against
      SICD. Characterization of triclabendazole revealed that it also protects yeast
      cells from death induced by the Parkinson's disease-related protein alpha
      synuclein (alpha-syn), which is known to induce the accumulation of ROS.

PMID- 21946066
TI  - Label-free THz sensing of living body-related molecular binding using a metallic
      mesh.
AB  - We have demonstrated label-free THz sensing of living body-related molecular
      binding using a thin metallic mesh and a polyvinylidene difluoride (PVDF)
      membrane. Metallic meshes in the THz region are designed for anomalous
      transmission phenomena derived from a resonant excitation of surface waves.
      Additionally, they are designed to have a sharp dip in transmittance. The
      metallic mesh is very sensitive to a change of the refractive index of materials
      attached to the metallic mesh. In this paper, we report sensing of interactions
      between lectin and sugar using this technique. We found that the dip frequency
      shift, transmittance attenuation of the dip frequency, and peak shift of the
      derivative spectrum of the phase shift depend on the bonding amount of lectin
      sugar interactions. We also applied this technique to detect avidin-biotin
      interactions, leading to the detection of a small amount of biotin (0.17
      pg/mm(2)).

PMID- 21946067
TI  - The role of 14-3-3beta in transcriptional activation of estrogen receptor alpha
      and its involvement in proliferation of breast cancer cells.
AB  - The estrogen receptor (ER) functions as a transcription factor that mediates the
      effects of estrogen. ERalpha, which plays a crucial role in the development and
      progression of breast cancer, is activated by estrogen binding, leading to
      receptor phosphorylation, dimerization, and recruitment of co-activators and
      chaperons to the estrogen-bound receptor complex. The 14-3-3 proteins bind to
      target proteins via phosphorylation and influence many cellular events by
      altering their subcellular localization or acting as a chaperone. However,
      regulation of ERalpha expression and transactivation by the 14-3-3 proteins has
      not been reported. We demonstrate that 14-3-3beta functions as a positive
      regulator of ERalpha through a direct protein-protein interaction in an estrogen
      dependent manner. Ectopic expression of 14-3-3beta stimulated ERalpha-mediated
      transcriptional activity in MCF-7 breast cancer cells. Enhanced ERalpha
      transcriptional activity due to 14-3-3beta increased the expressions of the
      endogenous ERalpha target genes, leading to proliferation of breast cancer cells.
      We suggest that 14-3-3beta has oncogenic potential in breast cancer via binding
      to ERalpha and activation of the transcriptional activity of ERalpha.

PMID- 21946068
TI  - Aldosterone increases kidney tubule cell oxidants through calcium-mediated
      activation of NADPH oxidase and nitric oxide synthase.
AB  - Chronic hyperaldosteronism has been associated with an increased cancer risk. We
      recently showed that aldosterone causes an increase in cell oxidants, DNA damage,
      and NF-kappaB activation. This study investigated the mechanisms underlying
      aldosterone-induced increase in cell oxidants in kidney tubule cells. Aldosterone
      caused an increase in both reactive oxygen and reactive nitrogen (RNS) species.
      The involvement of the activation of NADPH oxidase in the increase in cellular
      oxidants was demonstrated by the inhibitory action of the NADPH oxidase
      inhibitors DPI, apocynin, and VAS2870 and by the migration of the p47 subunit to
      the membrane. NADPH oxidase activation occurred as a consequence of an increase
      in cellular calcium levels and was mediated by protein kinase C. The prevention
      of RNS increase by BAPTA-AM, W-7, and L-NAME indicates a calcium-calmodulin
      activation of NOS. A similar pattern of effects of the NADPH oxidase and NOS
      inhibitors was observed for aldosterone-induced DNA damage and NF-kappaB
      activation, both central to the pathogenesis of chronic aldosteronism. In
      summary, this paper demonstrates that aldosterone, via the mineralocorticoid
      receptor, causes an increase in kidney cell oxidants, DNA damage, and NF-kappaB
      activation through a calcium-mediated activation of NADPH oxidase and NOS.
      Therapies targeting calcium, NOS, and NADPH oxidase could prevent the adverse
      effects of hyperaldosteronism on kidney function as well as its potential
      oncogenic action.

PMID- 21946069
TI  - Inhibitory effect of mulberroside A and its derivatives on melanogenesis induced
      by ultraviolet B irradiation.
AB  - Mulberroside A was isolated from the ethanol extract of Morus alba roots. The
      enzymatic hydrolysis of mulberroside A with Pectinex produced oxyresveratrol and
      oxyresveratrol-3-O-glucoside. We tested oxyresveratrol, oxyresveratrol-3-O
      glucoside, and mulberroside A to determine whether they could inhibit ultraviolet
      B (UVB) irradiation-induced melanogenesis in brown guinea pig skin. Topical
      application of mulberroside A, oxyresveratrol, and oxyresveratrol-3-O-glucoside
      reduced the pigmentation in guinea pig skin. These compounds suppressed the
      expression of melanogenic enzymes tyrosinase, tyrosinase-related protein-1, and
      microphthalmia transcription factor. The anti-melanogenesis effect was highest
      with oxyresveratrol, intermediate with oxyresveratrol-3-O-glucoside, and lowest
      with mulberroside A. Mulberroside A is a glycosylated stilbene of oxyresveratrol;
      thus, the deglycosylation of mulberroside A resulted in enhanced inhibition of
      melanogenesis. Histological analysis with Fontana-Masson staining confirmed that
      these compounds significantly reduced the melanin content in the epidermis of UVB
      irradiated guinea pig skin compared to the vehicle control. Thus, these compounds
      effectively reduced pigmentation and may be suitable cosmetic agents for skin
      whitening.

PMID- 21946070
TI  - Apocynin may limit total cell death following cerebral ischemia and reperfusion
      by enhancing apoptosis.
AB  - The present study was designed to determine a dose-response relationship between
      apocynin and infarct volume as well as to provide a possible molecular mechanism
      mediating this effect. We tested the hypothesis that apocynin protects against
      cell death following stroke and reperfusion injury. Apocynin was administered 30
      min prior to, or immediately following removal of sutures used to occlude the
      middle cerebral artery (MCA) in male Sprague-Dawley rats. Following removal of
      the sutures, the MCA was allowed to undergo 5.5h of reperfusion. Pretreatment
      with apocynin 30 min prior to occlusion resulted in a dose-dependent reduction in
      infarct volume by ~50 %. Analysis of tissue from the ischemic cortex of apocynin
      treated rats showed an increase in the level of glutathione (GSH), protein
      adducts (HNE-His), hydrogen peroxide (H(2)O(2)) and DNA fragmentation (apoptotic
      cell death) was also observed. This suggests that apocynin may increase
      antioxidant defense systems (GSH) to limit the degree of ischemia-induced
      cellular stress. In addition, this moderate cell stress results in more apoptotic
      vs necrotic cell death, and thus may limit the spreading depression and total
      cell death that occurs following ischemia/reperfusion. These effects may serve as
      a potential novel mechanism of action contributing to the apocynin-induced
      neuroprotection observed.

PMID- 21946071
TI  - Toxicological impact of technical imidacloprid on ovarian morphology, hormones
      and antioxidant enzymes in female rats.
AB  - Technical imidacloprid was evaluated for its effect on ovarian morphology,
      hormones and antioxidant enzymes in female rats after 90 days oral exposure.
      Luteinizing hormone (LH), follicle stimulating hormone (FSH) and progesterone
      levels were estimated in serum of rats and activity of superoxide dismutase
      (SOD), catalase (CAT), glutathione peroxidase (GPx) and level of reduced
      glutathione (GSH) and lipid peroxidation (LPO) were estimated in ovary after oral
      administration of imidacloprid (5, 10, and 20mg/kg/day) for 90 days. Decreased
      ovarian weight together with significant patho-morphological changes in
      follicles, antral follicles and atretic follicles were observed at 20mg/kg/day.
      Imidacloprid at 5 and 10mg/kg/day has not produced any significant changes in
      ovarian morphology, hormones and antioxidant status of ovary. However 20mg/kg/day
      dose has produced significant alterations in the levels of LH, FSH and
      progesterone. Similarly significant changes in SOD, CAT, GPx, GSH, and LPO were
      observed at 20mg/kg/day dose level. Therefore, it is concluded that imidacloprid
      at 20mg/kg/day dose level has produced significant toxicological impact on ovary
      of female rats as evident by pathomorphological changes, hormonal imbalance and
      generating oxidative stress and can be considered primarily as Lowest Observed
      Effect Level (LOEL) for chronic study.

PMID- 21946072
TI  - Algorithm for donor selection in 2011.
AB  - PURPOSE OF REVIEW: The timing represents a relevant prognostic factor of outcome
      for patients with hematological malignancies undergoing an allogeneic
      hematopoietic stem cell transplant (ASCT). In this review, the most recent
      studies and own transplant center policy on the donor search will be summarized
      in order to design an algorithm of donor identification driving towards a timely
      ASCT. RECENT FINDINGS: Nowadays, volunteer-unrelated, umbilical cord blood and
      haploidentical-related donors represent the three alternative sources of
      hematopoietic stem cells for patients who lack a human leukocyte antigen
      identical sibling, so that an alternative donor can potentially be found for
      about all patients eligible for an ASCT. To date, all retrospective studies
      comparing transplants from these alternative donors have shown no substantial
      differences in terms of final outcome of patients grafted for hematological
      malignancies. The policy of a widespread search for an alternative donor has been
      progressively increasing in the past years. SUMMARY: All patients with
      hematological malignancy for whom the intention to treatment includes an
      allogeneic transplant should proceed with a well timed ASCT, whatever the stem
      cell source. The therapeutic policy following the concept of 'donor versus no
      donor' should presently be changed according to the concept of 'transplant versus
      no transplant'.

PMID- 21946073
TI  - New thoughts on the correct dosing of prophylactic platelet transfusions to
      prevent bleeding.
AB  - PURPOSE OF REVIEW: Recent studies have evaluated the effects of platelet dose on
      hemostasis. RECENT FINDINGS: As long as a critical level of 5000  platelets/MUl
      is maintained, platelet counts do not affect bleeding. The risk of WHO grade 2 or
      greater bleeding was 25% on days with morning platelet counts of less than
      5000/MUl and was 17% at platelet counts between 6000 and 80 000/MUl (P < 0.001).
      Therefore, it is not surprising that platelet doses of half to twice the usual
      dose of 2.2 * 10(11)  platelets/transfusion/body surface area (BSA) do not affect
      any bleeding grade. However, the risk of grade 2 or greater bleeding is higher in
      patients receiving an allogeneic hematopoietic stem cell transplant (HSCT, 79%)
      versus those receiving chemotherapy for hematologic malignancies (73%) or those
      receiving an autologous HSCT (57%) (P < 0.001 for the latter versus the first two
      groups). In contrast, in children under 18, the risk of bleeding was higher in
      all treatment groups than in adults, particularly for children receiving
      autologous HSCT (93 to 83% based on increasing patient age). However, for none of
      these treatment categories did platelet dose affect bleeding risk. SUMMARY:
      Platelet doses in ranges between half to twice the usual dose of 2.2 * 10(11) 
      platelets/transfusion/BSA have no affect on WHO bleeding grades.

PMID- 21946074
TI  - Eosinophilic oesophagitis:  an Irish experience.
AB  - INTRODUCTION: Eosinophilic oesophagitis is a recently recognized oesophageal
      disorder characterized by a combination of clinical and endoscopic features as
      well as the histological finding on oesophageal biopsy of greater than 15
      eosinophils per high powered field. Recent reports suggest eosinophilic
      oesophagitis is increasing in incidence and this increase cannot be fully
      explained by increased recognition of the disorder. The aim of this retrospective
      study was to assess the incidence of eosinophilic oesophagitis within the
      catchment area of a tertiary referral hospital in southwest Dublin, Ireland.
      METHODS: The histopathology database at the Adelaide and Meath Hospital was used
      to identify all oesophageal biopsies obtained between January 2000 and July 2008
      reported to show evidence of oesophagitis. Biopsy samples with greater than 15
      eosinophils per high powered field in at least two fields were highlighted as
      possible eosinophilic oesophagitis. The oesophageal biopsies of patients
      identified in this way were reviewed by a histopathologist with a special
      expertise in gastroenterology for features suggestive of eosinophilic
      oesophagitis. RESULTS: Twenty-five thousand three hundred and sixty-five upper
      gastrointestinal endoscopies were performed between January 2000 and July 2008. A
      total of 11 072 sets of oesophageal biopsies were taken and 1364 (12.3%) of these
      revealed evidence of oesophagitis. Only 13 (0.1%) patients had oesophageal
      biopsies showing greater than 15 eosinophils per high powered field. The median
      age of this patient group was 23 years (interquartile range 10.5-50.5 years),
      with 46% of patients under 18 years at the time of diagnosis. The male to female
      ratio was 5.5 : 1 compared with 1.1 : 1 in the oesophagitis group as a whole,
      (P=0.002). There was no significant association between endoscopic findings or
      presenting complaints and the average number of eosinophils per high powered
      field. The average number of biopsies taken in patients with endoscopic findings
      suggestive of eosinophilic oesophagitis was 3.75 compared with 1 in patients
      without those features, (P=0.01). CONCLUSION: Our findings suggest that
      eosinophilic oesophagitis is a rare disorder predominantly affecting young men.

PMID- 21946075
TI  - Intestinal microvascular malformations and congenital asplenia in an adolescent
      possibly expanding the phenotype of Ivemark syndrome.
AB  - Intestinal vascular malformations in children and adolescents are rare but must
      be considered in the differential diagnosis of gastrointestinal bleeding and
      chronic anemia. We report a 16-year-old girl who developed chronic iron
      deficiency anemia due to recurrent bleeding from multiple angiodysplastic lesions
      of the stomach, duodenum, and jejunum. The cause of blood loss remained unclear
      for several years while the girl received numerous blood transfusions. Diagnosis
      was finally established by capsule endoscopy and double-balloon enteroscopy.
      Treatment was effectively carried out by argon plasma coagulation. Many systemic
      vascular malformation syndromes are associated with gastrointestinal lesions.
      However, as no extraintestinal vascular lesions were present in our patient,
      diagnosis of a known vascular malformation syndrome seemed unlikely. In addition
      to the microvascular intestinal malformations, we found a familial congenital
      asplenia without apparent infectious complications. Thus, the reported case
      possibly constitutes a so far unpublished variant of the Ivemark syndrome without
      macrovascular malformations but instead with microvascular malformations. We
      therefore envison that in times of refined diagnostic techniques the phenotype of
      the Ivemark syndrome might be expanded by including microvascular malformations.

PMID- 21946076
TI  - Cross-link immunoprecipitation data to detect polymorphisms lying in splicing
      regulatory motifs:  a method to refine single nucleotide polymorphism selection
      in association studies.
AB  - In a previous study we showed that prediction tools are useful to select single
      nucleotide polymorphisms (SNPs) which potentially affect phenotype and therefore
      guide genotyping in association studies, thus saving time and money. Here we use
      the recently available RNA cross-link immunoprecipitation data to analyze several
      genes involved in psychiatric disorders and show which disease-associated SNPs
      can affect the splicing process by altering splicing factor binding sites. We
      point out the importance of using cross-link immunoprecipitation data in
      psychiatry to refine the SNP selection methods, to explain the association found
      and to plan molecular investigations.

PMID- 21946077
TI  - Chemical compositions and bioactivities of crude polysaccharides from tea leaves
      beyond their useful date.
AB  - The chemical compositions and bioactivities of crude tea polysaccharides (TPS)
      from the out-of-date tea leaves (beyond their useful date), namely Xihu Longjing
      (XTPS), Anxi Tieguanyin (TTPS), Chawentianxia (CTPS) and Huizhoulvcha (HTPS), in
      market were investigated. These TPS showed similar neutral sugar content and
      different distribution of molecular weight (1-800 kD). These crude TPS were
      mainly composed of rhamnose, arabinose, galactose, glucose, xylose, mannose, and
      galacturonic acid. IR spectra confirmed that these crude TPS were composed of
      polysaccharide, protein and uronic acids. These TPS showed similar DPPH
      scavenging activity and exhibited lower DPPH scavenging activities than Vc within
      25-200 MUg/mL. However, these TPS with higher concentrations (200-400 MUg/mL)
      showed similar DPPH scavenging activity with Vc. HTPS exhibited significant
      higher superoxide anion scavenging activity than others TPS and gallic acid. XTPS
      showed significant higher inhibitory effects on alpha-glucosidase and alpha
      amylase with inhibitory percentages of 64.35% and 82.24% than others TPS. TTPS,
      XTPS, and HTPS exhibited similar inhibition ability on alpha-d-glucosidase and
      alpha-amylase. The overdue tea leaves can be a resource of tea polysaccharides as
      function food.

PMID- 21946078
TI  - In-situ silica incorporated carboxymethyl tamarind: development and application
      of a novel hybrid nanocomposite.
AB  - A novel hybrid nanocomposite has been prepared using in situ incorporation of
      nano-sized filler (silica) onto carboxymethyl tamarind kernel polysaccharide
      (CMT). Various characterizations were employed to confirm that silica nano
      particles have been incorporated onto the polymer matrix. Rheological
      characteristics reveal stronger CMT-Si interaction at 0.5 and 1 wt% level. Beyond
      1 wt% Si concentration, the interaction is less and so there is little drop in
      shear viscosity. Flocculation efficiency increases with incorporation of nano
      filler, maximum efficacy being observed at 1 wt% silica concentration. All the
      nanocomposites exhibited better flocculation characteristics in comparison to
      pure CMT.

PMID- 21946079
TI  - Glucose and pH dual-responsive concanavalin A based microhydrogels for insulin
      delivery.
AB  - Glucose and pH dual-responsive microhydrogels based on concanavalin A (Con A)
      were prepared and used for insulin delivery. The combination of the specific
      saccharide-binding affinity of Con A and the cationic groups of N-(2
      (dimethylamino) ethyl)-methacrylamide (DMAEMA) led to dual-responsive systems.
      SEM, fluorescence microscopy and particle size analysis showed that the obtained
      microhydrogels had a dense surface morphology and an average size of 38 MUm. The
      in vitro insulin release study revealed that the microhydrogels could quickly
      respond to the changes of glucose concentrations in the medium and small change
      in pH value of the environment. The kinetics of insulin release was analyzed by
      using empirical equation and the apparent diffusion coefficient was calculated
      according to a solution of Fick's second law. The released insulin was proved to
      remain active. The result suggested that this microhydrogel might find potential
      applications for self-regulated insulin delivery, actuators and separation
      systems with sensitivity to glucose.

PMID- 21946080
TI  - Estimation of physical activity levels using cell phone questionnaires: a
      comparison with accelerometry for evaluation of between-subject and within
      subject variations.
AB  - BACKGROUND: Physical activity promotes health and longevity. Further elaboration
      of the role of physical activity for human health in epidemiological studies on
      large samples requires accurate methods that are easy to use, cheap, and possible
      to repeat. The use of telecommunication technologies such as cell phones is
      highly interesting in this respect. In an earlier report, we showed that physical
      activity level (PAL) assessed using a cell phone procedure agreed well with
      corresponding estimates obtained using the doubly labeled water method. However,
      our earlier study indicated high within-subject variation in relation to between
      subject variations in PAL using cell phones, but we could not assess if this was
      a true variation of PAL or an artifact of the cell phone technique. OBJECTIVE:
      Our objective was to compare within- and between-subject variations in PAL by
      means of cell phones with corresponding estimates using an accelerometer. In
      addition, we compared the agreement of daily PAL values obtained using the cell
      phone questionnaire with corresponding data obtained using an accelerometer.
      METHODS: PAL was measured both with the cell phone questionnaire and with a
      triaxial accelerometer daily during a 2-week study period in 21 healthy Swedish
      women (20 to 45 years of age and BMI from 17.7 kg/m2 to 33.6 kg/m2). The results
      were evaluated by fitting linear mixed effect models and descriptive statistics
      and graphs. RESULTS: With the accelerometer, 57% (95% confidence interval [CI]
      40%-66%) of the variation was within subjects, while with the cell phone, within
      subject variation was 76% (95% CI 59%-83%). The day-to-day variations in PAL
      observed using the cell phone questions agreed well with the corresponding
      accelerometer results. CONCLUSIONS: Both the cell phone questionnaire and the
      accelerometer showed high within-subject variations. Furthermore, day-to-day
      variations in PAL within subjects assessed using the cell phone agreed well with
      corresponding accelerometer values. Consequently, our cell phone questionnaire is
      a promising tool for assessing levels of physical activity. The tool may be
      useful for large-scale prospective studies.

PMID- 21946082
TI  - Evidence for extended YFP-EGFR dimers in the absence of ligand on the surface of
      living cells.
AB  - The epidermal growth factor receptor (EGFR) is a member of the erbB tyrosine
      kinase family of receptors. Structural studies have revealed two distinct
      conformations of the ectodomain of the EGFR: a compact, tethered, conformation
      and an untethered extended conformation. In the context of a monomer-dimer
      transition model, ligand binding is thought to untether the monomeric receptor
      leading to exposure of a dimerization arm which then facilitates receptor
      dimerization, kinase activation and signaling. For receptors directed orthogonal
      to the local plane of the membrane surface, this would lead to a large change in
      the distance of the receptor N-terminus from the membrane surface. To investigate
      this experimentally, we produced stable BaF/3 cell lines expressing a
      biochemically functional yellow fluorescent protein (YFP)-EGFR chimera and
      determined the vertical separation of the N-terminal YFP tag from the membrane
      using fluorescence resonance energy transfer (FRET) techniques. Homo-FRET/rFLIM
      was employed to determine the presence of unliganded dimers and to measure the
      average distance between the N-terminal tags in those dimers. The results suggest
      that EGF-induced activation occurs within or between pre-formed and extended
      dimers with very little change in the extension of the N-terminii from the
      membrane surface. These results provide constraints on possible models for EGFR
      activation.

PMID- 21946083
TI  - Gambogic acid inhibits tumor cell adhesion by suppressing integrin beta1 and
      membrane lipid rafts-associated integrin signaling pathway.
AB  - Cell adhesion plays an important role in the steps of cancer metastasis.
      Regulation of cell-cell (intercellular) and cell-matrix adhesion is a promising
      strategy for cancer progression. Gambogic acid is a xanthone derived from the
      resin of the Chinese plant Garciania hanburyi, with potent anti-metastasis
      activity on highly metastatic cells. The aim of this study was to investigate the
      function and mechanism of gambogic acid on tumor adhesion. We found that gambogic
      acid strongly inhibited the adhesion of human cancer cells to fibronectin. This
      inhibition was associated with the deformation of focal adhesion complex, which
      was mediated by suppressing the expression of integrin beta1 and integrin
      signaling pathway. In vitro, cell lipid rafts clustering was inhibited following
      treatment of gambogic acid, which induced the suppression of integrin beta1 and
      focal adhesion complex proteins colocalization within rafts. Moreover, gambogic
      acid significantly decreased cellular cholesterol content, whereas cholesterol
      replenishment lessened the inhibitory effect of gambogic acid on cell adhesion.
      Real-time PCR analysis showed that gambogic acid reduced mRNA levels of
      hydroxymethylglutaryl-CoA reductase and sterol regulatory element binding protein
      2, while increased acetyl-CoA acetyltransferase-1/2. Taken together, these
      results demonstrate that gambogic acid inhibits cell adhesion via suppressing
      integrin beta1 abundance and cholesterol content as well as the membrane lipid
      raft-associated integrin function, which provide new evidence for the anti-cancer
      activity of gambogic acid.

PMID- 21946081
TI  - Catabolic and anabolic actions of parathyroid hormone on the skeleton.
AB  - PTH, an 84-amino acid peptide hormone synthesized by the parathyroid glands, is
      essential for the maintenance of calcium homeostasis.While in its traditional
      metabolic role, PTH helps to maintain the serum calcium concentration within
      narrow, normal limits and participates as a determinant of bone remodeling, more
      specific actions, described as catabolic and anabolic are also well known.
      Clinically, the catabolic effect of PTH is best represented by primary
      hyperparathyroidism (PHPT), while the osteoanabolic effect of PTH is best seen
      when PTH or its biological amino-terminal fragment [PTH(1-34)] is used as a
      therapy for osteoporosis. These dual functions of PTH are unmasked under very
      specific pathological (PHPT) or therapeutic conditions. At the cellular level,
      PTH favors bone resorption, mostly by affecting the receptor activator of nuclear
      factor kappa-B (RANK) ligand (RANKL)-osteoprotegerin- RANK system, leading to an
      increase in osteoclast formation and activity. Increased bone formation due to
      PTH therapy is explained best by its ability to enhance osteoblastogenesis and/or
      osteoblast survival. The PTH-induced bone formation is mediated, in part, by a
      decrease in SOST/sclerostin expression in osteocytes. This review focuses on the
      dual anabolic and catabolic actions of PTH on bone, situations where one is
      enhanced over the other, and the cellular and molecular mechanisms by which these
      actions are mediated.

PMID- 21946084
TI  - Insulin deficiency induces abnormal increase in intestinal disaccharidase
      activities and expression under diabetic states, evidences from in vivo and in
      vitro study.
AB  - Structural and functional alterations in the gastrointestinal tract of diabetic
      patients are often accompanied by increase in absorption of intestinal glucose
      and activities of brush-border disaccharidases. The purpose of this study was to
      investigate the role of insulin in regulating intestinal disaccharidases using in
      vivo and in vitro experiments. Streptozotocin-induced diabetic rats and normal
      rats received protamine zinc insulin (10 IU/kg) subcutaneously twice daily for 5
      weeks. Disaccharidase activities and sucrase-isomaltase (SI) complex protein and
      mRNA expression in intestinal regions were assessed. In addition, Caco-2 cells
      were cultured in medium containing glucose, insulin or insulin plus some
      pharmacological inhibitors for 7 days, disaccharidase activities, sucrase
      isomaltase (SI) complex and Cdx2 mRNA levels were measured. The animal
      experiments showed that diabetes increased intestinal disaccharidase activities,
      accompanied by high mRNA and protein expression of SI complex. Insulin treatment
      reversed the increases induced by diabetes. The cellular results showed that
      insulin suppressed disaccharidase activities and down-regulated SI complex and
      Cdx2 mRNA expression in a concentration-dependent manner. The inhibitor of MAPK
      signal pathway PD-98059 blocked the suppression of disaccharidase activities and
      expression of SI complex and Cdx2 mRNA induced by insulin. In conclusion, insulin
      deficiency induces abnormal increase in intestinal disaccharidase activities and
      expression under diabetic states. Insulin plays an essential role in regulation
      disaccharidase activities and expression, at least in part, via the MAPK
      dependent pathway.

PMID- 21946085
TI  - Emerging insights into the molecular biology of brain metastases.
AB  - One of the foremost challenges in oncology is developing improved therapies for
      preventing and treating metastases to the brain. Recent research in this area is
      bringing about a shift in the understanding of brain metastases. Previously, the
      occurrence and poor outcomes associated with brain metastases have been largely
      attributed to the exclusion of anticancer drugs from the brain by the blood-brain
      barrier (BBB). However, studies in multiple tumor types have also demonstrated
      that brain metastases have significant molecular differences from primary tumors
      and extracranial metastases. These molecular differences may not only promote the
      formation of brain metastases, but they may also contribute to these tumors' poor
      responsiveness to therapies. Such changes may be intrinsic to the cancer cells or
      driven by unique interactions with the brain microenvironment. An improved
      understanding of the molecular characteristics of brain metastases that
      contribute to their aggressive behaviors will facilitate the development of
      rational, more effective treatments for these tumors.

PMID- 21946087
TI  - Validity of two self-report measures of sitting time.
AB  - BACKGROUND: In light of evidence linking sedentary behaviors to health outcomes,
      there have been calls for the measurement of sedentary behavior in surveillance
      studies. This study examined the convergent validity of 2 self-report measures of
      sitting time and accelerometer-determined sedentary time (minutes/day of <100
      counts/minute). METHODS: 44 adults wore an ActiGraph accelerometer for 7 days,
      during which they also recorded daily sitting time in a diary, in response to a
      single-item question. After 7 days, participants completed a new domain-specific
      questionnaire to assess usual weekday and weekend-day sitting time. Total sitting
      times recorded from the self-report measures were compared with accelerometer
      determined sedentary time. RESULTS: Total sitting time calculated from the domain
      specific questionnaire did not differ significantly from accelerometer-determined
      sedentary time on weekdays (mean difference [+/-SE] = -14 +/- 28 mins/day) and
      weekend days (-4 +/- 45 mins/day, both P > .05). Sitting time was significantly
      underestimated using the single-item specific-day question on weekdays (-173 +/-
      18 mins/day) and weekend days (-219 +/- 23 mins/day, both P < .001). CONCLUSIONS:
      When assessed via self-report, the estimation of total sitting time is improved
      by summing sitting times reported across different domains. The continued
      improvement of self-report measures of sitting time will be important if we are
      to further our understanding of the links between sedentary behavior and health.

PMID- 21946086
TI  - High density micromass cultures of a human chondrocyte cell line: a reliable
      assay system to reveal the modulatory functions of pharmacological agents.
AB  - Osteoarthritis is a highly prevalent and disabling disease for which we do not
      have a cure. The identification of suitable molecular targets is hindered by the
      lack of standardized, reproducible and convenient screening assays. Following
      extensive comparisons of a number of chondrocytic cell lines, culture conditions,
      and readouts, we have optimized an assay utilizing C-28/I2, a chondrocytic cell
      line cultured in high-density micromasses. Utilizing molecules with known effects
      on cartilage (e.g. IL-1beta, TGFbeta1, BMP-2), we have exploited this improved
      protocol to (i) evoke responses characteristic of primary chondrocytes; (ii)
      assess the pharmacodynamics of gene over-expression using non-viral expression
      vectors; (iii) establish the response profiles of known pharmacological
      treatments; and (iv) investigate their mechanisms of action. These data indicate
      that we have established a medium-throughput methodology for studying chondrocyte
      specific cellular and molecular responses (from gene expression to rapid
      quantitative measurement of sulfated glycosaminoglycans by Alcian blue staining)
      that may enable the discovery of novel therapeutics for pharmacological
      modulation of chondrocyte activation in osteoarthritis.

PMID- 21946088
TI  - Characterization of the Cullin7 E3 ubiquitin ligase--heterodimerization of cullin
      substrate receptors as a novel mechanism to regulate cullin E3 ligase activity.
AB  - Cul1 and Cul7 are cullin E3 ubiquitin ligase scaffold proteins. Cul1 is known to
      form a complex with the RING domain protein Rbx1 and one of approximately 70
      different F-box proteins. F-box proteins function as substrate receptor subunits
      and recruit numerous substrates for poly-ubiquitination. Similarly to Cul1, Cul7
      interacts with Rbx1, however, only one F-box protein, Fbxw8, has been shown to
      bind to Cul7. To date only few Cul7 E3 ubiquitin ligase substrates, including
      cyclin D1, IRS-1 and GRASP65, have been reported, and using Fbxw8 affinity
      purification, we were unable to identify additional substrate proteins. Here we
      provide evidence for a model in which Cul7-Rbx1 can promote the ubiquitination of
      Cul1 substrates by forming high order complexes with Cul1-Rbx1. Binding of Cul1
      Rbx1 to Cul7-Rbx1 is mediated via heterodimerization of Fbxw8 with other F-box
      proteins which function to recruit substrates into the E3 ligase complex. The
      formation of this high order complex is likely to increase polyubiquitination
      efficiency.

PMID- 21946089
TI  - The "muffin test"--an alternative to the oral glucose tolerance test for
      detecting impaired glucose tolerance.
AB  - OBJECTIVE: The aim of this study was to compare the effectiveness of the "muffin
      test" (MT) with that of the oral glucose tolerance test (OGTT) in diagnosing
      impaired glucose tolerance (IGT). METHODS: This is a cross-sectional study in a
      single academic institution. The participants were 73 women aged 42 to 58 years,
      less than 36 months after menopause, recruited for the Kronos Early Estrogen
      Prevention Study Trial. After a 10-hour fasting blood draw, the participants were
      provided a muffin and a beverage. Two-hour glucose levels were assessed. A subset
      underwent metabolic testing consisting of an OGTT (n = 12) and a mixed-meal
      tolerance test (n = 10). The main outcome measures were the prevalence of IGT and
      2-hour glucose measurements after each testing method. RESULTS: Two-hour glucose
      levels were linearly related to fasting values by multivariable linear
      regression. This association was exaggerated in overweight (body mass index, 25
      kg/m2) women (coefficient, 1.43; P < 0.001). Two-hour OGTT and MT glucose levels
      were comparable (P > 0.05); 2-hour glucose levels after OGTT were slightly lower
      than after the mixed-meal tolerance test (P < 0.05). CONCLUSIONS: The prevalence
      of IGT was 11% (8 of 73). Fasting plasma glucose alone would have missed 63% of
      cases (five of eight cases). The MT demonstrated 100% sensitivity and specificity
      for diagnosing IGT compared with the gold standard OGTT. This small pilot study
      should be confirmed in a larger prospective group of participants.

PMID- 21946090
TI  - Meta-analysis suggests that smoking is associated with an increased risk of early
      natural menopause.
AB  - OBJECTIVE: Age at natural menopause (ANM) is usually defined as the age at the
      last menstrual bleeding followed by the absence of menses for 12 consecutive
      months. Although many studies have suggested an association between smoking and
      early age at natural menopause, evidence remains conflicting because some studies
      reported inconsistent or contrasting results. To resolve this ambiguity and to
      quantitatively evaluate the effect of smoking on ANM, we conducted a meta
      analysis of the available data about smoking and ANM. METHODS: After extensive
      searching of public literature databases, a total of 11 studies were selected for
      this meta-analysis. Among them, the phenotype of the participants in five studies
      (dichotomous studies) was classified as early or late ANM, and odds ratio (OR)
      was used to evaluate the effect of smoking on early ANM. For the other six
      studies (continuous studies), mean and SD were provided for smoking and
      nonsmoking samples, and weighted mean difference (WMD) was used as the effect
      size. RESULTS: We found that smoking was significantly associated with early ANM
      in both dichotomous and continuous studies. The pooled effect was OR = 0.74 (95%
      CI, 0.60-0.91, P < 0.01) in the dichotomous studies. For the continuous studies,
      the pooled effect estimated by WMD was -1.12 (95% CI, -1.80 to -0.44, P = 0.04).
      After adjustment of the original data for heterogeneity, the pooled results
      changed only a little: OR = 0.67 (95% CI, 0.61-0.73, P < 0.01) for dichotomous
      studies and WMD = -0.90 (95% CI, -1.58 to -0.21, P = 0.01) for the continuous
      studies. CONCLUSIONS: The results of our study suggest that smoking is a
      significant independent factor for early ANM.

PMID- 21946091
TI  - Ventilator-induced lung injury in healthy and diseased lungs: better to prevent
      than cure!

PMID- 21946093
TI  - What we know: precise measurement leads to patient comfort and safety.

PMID- 21946094
TI  - Intraoperative acceleromyography monitoring reduces symptoms of muscle weakness
      and improves quality of recovery in the early postoperative period.
AB  - BACKGROUND: The subjective experience of residual neuromuscular blockade after
      emergence from anesthesia has not been examined systematically during
      postanesthesia care unit (PACU) stays. The authors hypothesized that
      acceleromyography monitoring would diminish unpleasant symptoms of residual
      paresis during recovery from anesthesia by reducing the percentage of patients
      with train-of-four ratios less than 0.9. METHODS: One hundred fifty-five patients
      were randomized to receive intraoperative acceleromyography monitoring
      (acceleromyography group) or conventional qualitative train-of-four monitoring
      (control group). Neuromuscular management was standardized, and extubation was
      performed when defined criteria were achieved. Immediately upon a patient's
      arrival to the PACU, the patient's train-of-four ratios were measured using
      acceleromyography, and a standardized examination was used to assess 16 symptoms
      and 11 signs of residual paresis. This examination was repeated 20, 40, and 60
      min after PACU admission. RESULTS: The incidence of residual blockade (train-of
      four ratios less than 0.9) was reduced in the acceleromyography group (14.5% vs.
      50.0% control group, with the 99% confidence interval for this 35.5% difference
      being 16.4-52.6%, P < 0.0001). Generalized linear models revealed the
      acceleromyography group had less overall weakness (graded on a 0-10 scale) and
      fewer symptoms of muscle weakness across all time points (P < 0.0001 for both
      analyses), but the number of signs of muscle weakness was small from the time of
      arrival in the PACU and did not differ between the groups at any time.
      CONCLUSION: Acceleromyography monitoring reduces the incidence of residual
      blockade and associated unpleasant symptoms of muscle weakness in the PACU and
      improves the overall quality of recovery.

PMID- 21946095
TI  - Seasonal variation of vocal behaviour in a temperate songbird: assessing the
      effects of laboratory housing on wild-caught, seasonally breeding birds.
AB  - Many laboratories are conducting research using songbirds as their animal model.
      In particular, songbirds are widely used for studying the behavioural and neural
      mechanisms underlying vocal learning. Many researchers use wild-caught birds to
      conduct this research, although few studies of behaviour have been conducted to
      determine the effects of captive housing on these species. We investigated the
      vocal production pattern of wild-caught black-capped chickadees (Poecile
      atricapillus) over an entire season in laboratory housing. We documented the
      frequency of production of four vocalizations (fee-bee song, chick-a-dee calls,
      dee calls, and gargle calls) across seasons and diurnal pattern and compared the
      observed pattern of laboratory vocalizations to those previously observed and
      reported in the wild. Laboratory-housed chickadees had seasonal and diurnal vocal
      production shifts that were related to both photoperiodic changes (season) and
      diurnal pattern. For instance, there was significantly more fee-bee song in the
      spring than summer, autumn, and winter with the most fee-bee song occurring at
      spring dawn as seen in the wild. Our results also confirmed that the general
      pattern of vocalizations was consistent between wild and laboratory populations,
      with no significant differences for either the seasonal or diurnal pattern of fee
      bee song production between populations. Differences between settings were
      observed in the pattern of chick-a-dee calls at dawn and sunset between field and
      laboratory populations. However, differences in the quantity of vocalization
      types between laboratory and wild populations suggest that housing conditions are
      influencing the normal vocal behavioural patterns.

PMID- 21946096
TI  - Relations between delay discounting and low to moderate gambling, cannabis, and
      alcohol problems among university students.
AB  - Research has generally demonstrated that the discounting of delayed rewards is
      associated with severity of addictive behaviour. Less clear, however, is the
      relative strength of the relation for specific addictive behaviours. University
      students (N=218) completed a computerized delay discounting task for hypothetical
      monetary rewards, and gambling, cannabis, and alcohol problem severity was
      assessed. A multiple regression analysis revealed that while the overall model
      was significant, only gambling problem severity accounted for delay discounting
      scores above and beyond cannabis and alcohol problem severity. The results
      support the hypothesis that delay discounting of hypothetical monetary rewards is
      more associated with gambling than other addictive behaviour problems, including
      substance use problems.

PMID- 21946097
TI  - Cathepsin B from the white shrimp Litopenaeus vannamei: cDNA sequence analysis,
      tissues-specific expression and biological activity.
AB  - Cathepsin B is a cystein proteinase scarcely studied in crustaceans. Its function
      has not been clearly described in shrimp species belonging to the sub-order
      Dendrobranchiata, which includes the white shrimp Litopenaeus vannamei and other
      species from the Penaeidae family. Studies on vertebrates suggest that these
      lysosomal enzymes intracellularly hydrolize protein, as other cystein
      proteinases. However, the expression of the gene encoding the shrimp cathepsin B
      in the midgut gland was affected by starvation in a similar way as other
      digestive proteinases which extracellularly hydrolyze food protein. In this study
      the white shrimp L. vannamei cathepsin B (LvCathB) cDNA was sequenced, and
      characterized. Its gene expression was evaluated in various shrimp tissues, and
      changes in the mRNA amounts were compared with those observed on other digestive
      proteinases from the midgut gland during starvation. By using qRT-PCR it was
      found that LvCathB is expressed in most shrimp tissues except in pleopods and eye
      stalk. Changes on LvCathB mRNA during starvation suggest that the enzyme
      participates during intracellular protein hydrolysis but also, after food
      ingestion, it participates in hydrolyzing food proteins extracellularly as
      confirmed by the high activity levels we found in the gastric juice and midgut
      gland of the white shrimp.

PMID- 21946098
TI  - Cloning and differential expression pattern of pituitary adenylyl cyclase
      activating polypeptide and the PACAP-specific receptor in darkbarbel catfish
      Pelteobagrus vachelli.
AB  - Pituitary adenylyl cyclase-activating polypeptide (PACAP) can mediate growth
      hormone and gonadotropin release in teleost pituitary via PACAP receptors. In
      this study, the full-length cDNAs encoding PACAP and PACAP-related peptide (PRP)
      and the PACAP-specific receptor (PAC1-R) were cloned from the brain of darkbarbel
      catfish Pelteobagrus vachelli. The PRP-PACAP cDNA had two variants expressed by
      alternative splicing: a long form encoding both PRP and PACAP and a short form
      encoding PACAP only. Our data showed that the exon skipping on the PACAP
      transcripts was a possible mechanism regulating the expression ratio of PACAP to
      PRP in non-mammalian vertebrates. Based on multi-sequence alignments and
      phylogenetic analysis, the catfish PACAP and PAC1-R were highly conserved during
      evolution. Real-time quantitative PCR revealed that the PACAP-short and PAC1-R
      tanscripts were mainly expressed in the brain and gonad of darkbarbel catfish,
      though a small amount of mRNAs was also found in other tissues. Immunofluorescent
      staining studies showed wide distribution and high levels of PAC1-R in the
      catfish brain, suggesting that the PAC1-R form may play a central role in growth
      hormone release. The expressions of PACAP and PAC1-R in gonads and the occurrence
      of PACAP-immunoreactive material in testis suggest that PACAP may act as a
      paracrine/autocrine factor for gonad development.

PMID- 21946099
TI  - Genetic characterization of the Psilotrema (Digenea: Psilostomatidae) genus by
      partial 28S ribosomal DNA sequences.
AB  - In the present study, we successfully amplified the 28S ribosomal DNA of 3
      species of the Psilotrema genus (Psilotrema oschmarini Besprozvannykh, 2007, P.
      acutirostris Oschmarin, 1963 and P. simillimum Muhling, 1989) from the Russian
      Far East. The genetic divergence between these species was estimated, and the
      phylogenetic relationships of the Psilotrema genus and the Psilostomatidae family
      were inferred. The resulting data support the independent taxonomical status of
      P. oschmarini as a valid species in the Russian Far East. In spite of the
      considerable morphological differences between P. simillimum and P. acutirostris,
      these species are genetically very close to each other. Genetic distances,
      calculated from the pairwise comparison of two obtained clusters using
      transversions, show that Psilostomatidae is the most divergent family.
      Phylogenetic analysis revealed two clusters, which corresponds to family
      Psilostomatidae (basal cluster) and other Echinostomatoidea species.

PMID- 21946100
TI  - Modulation of the expression of ABC transporters in murine (J774) macrophages
      exposed to large concentrations of the fluoroquinolone antibiotic moxifloxacin.
AB  - Long-term exposure to pharmacological agents can select for cells that
      overexpress efflux transporters. We previously showed that mouse J774 macrophages
      cultivated for a prolonged period of time with toxic concentrations of the
      fluoroquinolone ciprofloxacin overexpress the efflux transporter Mrp4 and display
      a reduced accumulation of this antibiotic, but no change in the accumulation of
      moxifloxacin, a closely related molecule (Antimicrob. Agents Chemother. [2006]
      50, 1689-1695 and [2009] 53, 2410-2416). Because of this striking difference
      between the two fluoroquinolones, we have now examined the modifications in the
      expression of ABC efflux transporters induced by the prolonged exposure of J774
      macrophages to high concentrations of moxifloxacin. The resulting cell line
      showed (i) no difference in the accumulation of moxifloxacin but an increased
      accumulation and decreased efflux of ciprofloxacin; (ii) an overexpression of the
      multidrug transporters Abcb1a (P-gp), Abcc2 (Mrp2) and Abcg2 (Bcrp1), and a
      decreased expression of Abcc4 (Mrp4). While P-gp and Bcrp1 were functional, they
      did not modify the cellular accumulation of fluoroquinolones. The data show that
      exposing cells to high concentrations of a drug that is not affected by active
      efflux can trigger a pleiotropic response leading to a modulation in the
      expression of several transporters. These changes, however, are not sufficient to
      protect cells against the toxicity that fluoroquinolones may exert at large
      concentrations. They could also cause unanticipated drug interactions in vivo,
      should the drug exposure grossly exceed what is anticipated from its current
      registered use.

PMID- 21946101
TI  - SCH23390, a dopamine D1 receptor antagonist, suppressed scratching behavior
      induced by compound 48/80 in mice.
AB  - To clarify the mechanisms by which compound 48/80 (C48/80) induces scratching
      behavior, the involvement of dopamine D(1) receptors was investigated. The
      intracisternal (i.t.) administration of SCH23390 (1.0 MUg), a selective dopamine
      D(1) receptor antagonist, significantly decreased C48/80-induced scratching
      behavior in mice. These results suggest that dopamine D(1) receptors contribute
      to scratching behavior or the itch sensation induced by subcutaneous injection of
      C48/80 in mice. Co-administration of SCH23390 and C48/80 enhanced c-fos
      immunoreactivities in the peduncular part of the lateral hypothalamus (PLH),
      whereas the immunoreactivities in the other groups were unchanged. The
      dopaminergic system may be playing an important role in the suppression of C48/80
      induced scratching behavior by SCH23390.

PMID- 21946102
TI  - Effects of pentoxifylline and H-89 on epileptogenic activity of bucladesine in
      pentylenetetrazol-treated mice.
AB  - The present study shows interactive effects of pentoxifylline (PTX) as a
      phosphodiesterase (PDE) inhibitor, H-89 as a protein kinase A (PKA) inhibitor and
      bucladesine (db-cAMP) as a cAMP agonist on pentylenetetrazol (PTZ)-induced
      seizure in mice. Different doses of pentoxifylline (25, 50, 100 mg/kg),
      bucladesine (50, 100, 300 nM/mouse), and H-89 (0.05, 0.1, 0.2 mg/100g) were
      administered intraperitoneally (i.p.), 30 min before intravenous (i.v.) infusion
      of PTZ (0.5% w/v). In combination groups, the first and second components were
      injected 45 and 30 min before PTZ infusion. In all groups, the control animals
      received an appropriate volume of vehicle. Single administration of PTX had no
      significant effect on both seizure latency and threshold. Bucladesine
      significantly decreased seizure latency and threshold only at a high
      concentration (300 nM/mouse). Intraperitoneal administration of H-89 (0.2
      mg/100g) significantly increased seizure latency and threshold in PTZ-treated
      animals. All applied doses of bucladesine in combination with PTX (50 mg/kg)
      caused a significant reduction in seizure latency. Pretreatment of animals with
      PTX (50 and 100 mg/kg) attenuated the anticonvulsant effect of H-89 (0.2 mg/100g)
      in PTZ-exposed animals. H-89 (0.05, 0.2 mg/100g) prevented the epileptogenic
      activity of bucladesine (300 nM) with significant increase of seizure latency and
      seizure threshold. In conclusion, we showed that seizure activities were affected
      by pentoxifylline, H-89 and bucladesine via interactions with intracellular cAMP
      and cGMP signaling pathways, cyclic nucleotide-dependent protein kinases, and
      related neurotransmitters.

PMID- 21946103
TI  - Desensitization of adenosine A(1) receptors in rat immature cortical neurons.
AB  - Adenosine plays an important neuroprotective role in brain, usually mediated by
      the activation of adenosine A1 receptors. Prolonged activation of a G-protein
      coupled receptor generally leads to the partial loss of the responsiveness of
      receptor-mediated transduction pathways (desensitization). Rat immature cortical
      neurons were treated with 100 nM-N6-phenylisopropyladenosine (R-PIA), a selective
      A1 receptor agonist, and the effect on adenosine A1 receptor/adenylyl cyclase
      pathway was studied. Incubation with R-PIA for 6, 12, 24 and 48 h elicited a time
      dependent decrease in adenosine A1 receptors in plasma membranes (92, 58, 43 and
      26% of control, respectively), which was associated with variations in microsomal
      fraction (21, 56, 124 and 233% of control, respectively), suggesting the
      internalization and down-regulation of adenosine A1 receptors. Moreover, real
      time PCR assays showed a significant increase in mRNA levels coding adenosine A1
      receptor after the longest treatment period (48 h). In addition, alphaGi1-2
      protein levels detected in microsomes and mRNA levels coding alphaGi1 protein
      were increased after 48 h of treatment with R-PIA, suggesting the synthesis of
      new alphaGi1 proteins. Finally, adenylyl cyclase inhibition elicited by 2-Chloro
      N6-cyclopentyladenosine (CPA), a selective adenosine A1 receptor agonist, was
      significantly reduced after 12, 24 and 48h of treatment (37, 24 and 23%,
      respectively) as compared to controls (54%), suggesting the desensitization of
      adenosine A1 receptor/adenylyl cyclase pathway. These results suggest that
      adenosine A1 receptors desensitize slowly after prolonged receptor activation in
      immature cortical neurons, showing mechanisms of desensitization similar to those
      described not only in fetal but also in adult rat brain.

PMID- 21946104
TI  - The neuroprotective effects of phytoestrogen alpha-zearalanol on beta-amyloid
      induced toxicity in differentiated PC-12 cells.
AB  - Although favorable effects of estrogen replacement therapy on Alzheimer's disease
      on postmenopausal women have been recognized, an associated increased incidence
      of uterine and breast tumors has jeopardized the clinical use of estrogen.
      Phytoestrogen alpha-zearalanol (alpha-ZAL) is a reductive product of the
      Gibberella zeae metabolite and abundant in plants and vegetables, which has been
      shown to protect cell injury with low side-effects on uterine and breast. This
      study was designed to evaluate the neuroprotective effects of alpha-ZAL, on the
      cultured differentiated PC-12 cells, while 17beta-estradiol (17beta-E2) has been
      used as an estrogen positive control. Following a 24 h exposure of the cells to
      amyloid beta-peptide fragment 25-35 (Abeta25-35), a significant reduction in cell
      survival and activities of total superoxide dismutase (SOD) and glutathione
      peroxidase (GSH-Px), as well as increased of malondialdehyde (MDA) were observed.
      However, preincubation of the cells with alpha-ZAL or 17beta-E2 prior to Abeta25
      35 exposure elevated the cell survival and SOD and GSH-Px activities, and
      decreased the level of MDA. In addition, Abeta25-35 caused a significant cell
      apoptosis and increased apoptotic rate, accompanied by decreasing of bcl-2
      expression and increasing bax, caspase-3 expression, pretreatment of the cells
      with alpha-ZAL or 17beta-E2 ameliorated these changes induced by Abeta25-35.
      Taken together, these data indicated that the phytoestrogen alpha-ZAL may
      effectively antagonize Abeta25-35-induced cell toxicity by attenuating oxidative
      stress and apoptotic cell death, in a manner similar to 17beta-E2. Our results
      suggested that alpha-ZAL can be used as a potential substitute of 17beta-E2 in
      postmenopausal women for Alzheimer's disease prevention.

PMID- 21946105
TI  - Calpain-mediated dystrophin disruption may be a potential structural culprit
      behind chronic doxorubicin-induced cardiomyopathy.
AB  - The critical importance of dystrophin to cardiomyocyte contraction and
      sarcolemmal and myofibers integrity, led us to test the hypothesis that
      dystrophin reduction/loss could be involved in the pathogenesis of doxorubicin
      induced cardiomyopathy, in order to determine a possible specific structural
      culprit behind heart failure. Rats received total cumulative doses of doxorubicin
      during 2 weeks: 3.75, 7.5, and 15 mg/kg. Controls rats received saline. Fourteen
      days after the last injection, hearts were collected for light and electron
      microscopy, immunofluorescence and western blot. The cardiac function was
      evaluated 7 and 14 days after drug or saline. Additionally, dantrolene (5 mg/kg),
      a calcium-blocking agent that binds to cardiac ryanodine receptors, was
      administered to controls and doxorubicin-treated rats (15 mg/kg). This study
      offers novel and mechanistic data to clarify molecular events that occur in the
      myocardium in doxorubicin-induced chronic cardiomyopathy. Doxorubicin led to a
      marked reduction/loss in dystrophin membrane localization in cardiomyocytes and
      left ventricular dysfunction, which might constitute, in association with
      sarcomeric actin/myosin proteins disruption, the structural basis of doxorubicin
      induced cardiac depression. Moreover, increased sarcolemmal permeability suggests
      functional impairment of the dystrophin-glycoprotein complex in cardiac myofibers
      and/or oxidative damage. Increased expression of calpain, a calcium-dependent
      protease, was markedly increased in cardiomyocytes of doxorubicin-treated rats.
      Dantrolene improved survival rate and preserved myocardial dystrophin, calpain
      levels and cardiac function, which supports the opinion that calpain mediates
      dystrophin loss and myofibrils degradation in doxorubicin-treated rats. Studies
      are needed to further elucidate this mechanism, mainly regarding specific calpain
      inhibitors, which may provide new interventional pathways to prevent doxorubicin
      induced cardiomyopathy.

PMID- 21946106
TI  - New synthetic anti-inflammatory chrysin analog, 5,7-dihydroxy-8-(pyridine
      4yl)flavone.
AB  - To identify anti-inflammatory flavonoid derivatives with optimal chemical
      structures, various 8-heterocyclic-substituted chrysin derivatives were
      previously synthesized and their effects on prostaglandin E2 (PGE2) production
      from the lipopolysaccharide (LPS)-treated mouse macrophage cell line, RAW 264.7,
      were evaluated. Through this screening procedure, 5,7-dihydroxy-8-(pyridine
      4yl)flavone (C-721) among the derivatives was selected for further
      pharmacological study. Contrary to the parent molecule, chrysin, C-721 was found
      to potently inhibit PGE2 and NO production by LPS-treated RAW cells. The IC50
      values of C-721 were 6.2 and 22.6MUM, respectively, for cyclooxygenase-2 (COX-2)
      mediated PGE2 and inducible nitric oxide (iNOS)-mediated NO production. Western
      blotting and reverse transcriptase-polymerase chain reaction analysis
      demonstrated that this compound inhibited PGE2 production, at least in part, via
      COX-2 down-regulation and COX-2 inhibition, while C-721 primarily inhibited NO
      via down-regulation of iNOS expression. In addition, C-721 inhibited TNF-alpha
      and IL-6 production at 10-50 MUM. An in vivo study revealed that oral and
      intraperitoneal administration of C-721 showed 25.2%-44.3% inhibition against
      lambda-carrageenan-induced paw edema in mice at 10-100mg/kg. Furthermore, this
      compound significantly inhibited collagen-induced arthritis in mice when
      administered by intraperitoneal injection at 50mg/kg three times/week. Taken
      together, these results suggest that C-721 has the potential for use as a
      synthetic lead compound for development of a new anti-inflammatory agent.

PMID- 21946107
TI  - Sildenafil improves the beneficial hemodynamic effects exerted by atorvastatin
      during acute pulmonary thromboembolism.
AB  - We investigated whether atorvastatin has beneficial hemodynamic effects during
      acute pulmonary thromboembolism (APT) and whether sildenafil improves these
      effects. We studied the involvement of oxidative stress, matrix
      metalloproteinases (MMPs), and neutrophil activation. APT was induced with
      autologous blood clots (500 mg/kg) in anesthetized male lambs pretreated with
      atorvastatin (10 mg/kg/day, subcutaneously; 1 week) or vehicle (dimethyl
      sulfoxide 10% subcutaneously). Sildenafil (0.7 mg/kg intravenously) or saline
      infusions were performed 60 min after APT induction. Non-embolized control
      animals received saline. APT significantly increased pulmonary vascular
      resistance index (PVRI) and mean pulmonary artery pressure (MPAP) by
      approximately 310% and 258% respectively. While atorvastatin pretreatment
      attenuated these increases (~150% and 153%, respectively; P < 0.05), its
      combination with sildenafil was associated with lower increases in PVRI and MPAP
      (~32% and 36%, respectively). Gelatin zymography showed increased MMP-9 and MMP-2
      levels in the bronchoalveolar lavage, and increased MMP-9 levels in plasma from
      embolized animals. Atorvastatin pretreatment attenuated bronchoalveolar lavage
      MMP-2 increases. The combination of drugs blunted the MMPs increases in
      bronchoalveolar lavage and plasma (P < 0.05). Neutrophils accumulated in
      bronchoalveolar lavage after APT, and atorvastatin pretreatment combined with
      sildenafil (but not atorvastatin alone) attenuated this effect (P < 0.05). APT
      increased lung lipid peroxidation and total protein concentrations in
      bronchoalveolar lavage, thus indicating oxidative stress and alveolar-capillary
      barrier damage, respectively. Both increases were attenuated by atorvastatin
      pretreatment alone or combined with sildenafil (P < 0.05). We conclude that
      pretreatment with atorvastatin protects against the pulmonary hypertension
      associated with APT and that sildenafil improves this response. These findings
      may reflect antioxidant effects and inhibited neutrophils/MMPs activation.

PMID- 21946108
TI  - Direct formation of thienopyridine-derived nitrosothiols--just add nitrite!
AB  - Thienopyridines (ticlopidine, clopidogrel and prasugrel) are pro-drugs that
      require metabolism to exhibit a critical thiol group in the active form that
      binds to the P2Y12 receptor to inhibit platelet activation and prevent thrombus
      formation in vivo. We investigated whether these thienopyridines participate in S
      nitrosation (SNO) reactions that might exhibit direct anti-platelet behaviour.
      Optimum conditions for in vitro formation of thienopyridine-SNO formation were
      studied by crushing ticlopidine, clopidogrel or prasugrel into aqueous solution
      and adding sodium nitrite, or albumin-SNO. Ozone-based chemiluminescence
      techniques were utilised to specifically detect NO release from the SNO produced.
      Effect on agonist-induced platelet aggregation was monitored using light
      transmittance in a 96 well microplate assay. Pharmaceutical grade preparations of
      ticlopidine, clopidogrel and prasugrel were found to exhibit significant free
      thiol and formed SNO derivatives directly from anionic nitrite in water under
      laboratory conditions without the need for prior metabolism. Thienopyridine-SNO
      formation was dependent on pH, duration of mixing and nitrite concentration, with
      prasugrel-SNO being more favourably formed. The SNO moiety readily participated
      in trans-nitrosation reactions with albumin and plasma. Prasugrel-SNO showed
      significantly better inhibition of platelet aggregation compared with clopidogrel
      SNO, however when compared on the basis of SNO concentration these were equally
      effective (IC50=7.91 +/- 1.03 v/s 10.56 +/- 1.43 MUM, ns). Thienopyridine-derived
      SNO is formed directly from the respective base drug without the need for prior
      in vivo metabolism and therefore may be an important additional contributor to
      the pharmacological effectiveness of thienopyridines not previously considered.

PMID- 21946109
TI  - In vitro characterisation of the duration of action of the histamine-1 receptor
      antagonist azelastine.
AB  - Azelastine is a selective antagonist at the human histamine-1 receptor and is
      used clinically in the treatment of allergic rhinitis. In this study we have
      investigated its duration of action in vitro in an effort to characterise the
      receptor and tissue components involved. Chinese hamster ovary cell membrane
      fragments were used to determine the kinetics of azelastine at the H1 receptor in
      a radioligand binding assay. Further duration of action studies were completed in
      tissue preparations using guinea-pig trachea and human bronchus. In radioligand
      binding studies, azelastine reached steady state at the H1 receptor after
      approximately 41 min and exhibited a significantly slower dissociation rate
      constant from the receptor than the first generation antihistamine,
      diphenhydramine. In washout studies completed in guinea-pig and human airway in
      vitro tissue preparations, azelastine continued to antagonise the effects of
      histamine at the H1 receptor for at least 18 h post-washout of the antagonist.
      This outcome was reversed following removal of the epithelium from guinea-pig
      isolated tracheal strips. These studies indicate there is a tissue component
      contributing to azelastine's duration of action, in addition to its direct H1
      receptor binding, with evidence suggesting a role for the epithelial layer.

PMID- 21946110
TI  - Umbelliferone modulates gamma-radiation induced reactive oxygen species
      generation and subsequent oxidative damage in human blood lymphocytes.
AB  - The purpose of this study was to investigate the antioxidant potential of
      umbelliferone, 7-hydroxy coumarin, and its role in the protection against
      radiation-induced oxidative damage in cultured human blood lymphocytes. It was
      found that the antioxidant effect of umbelliferone was dose dependent in hydroxyl
      (OH(*)), superoxide anion (O(2)(*-)), 2,2-azino-bis-3-ethylbenzothiazoline-6
      sulphonic acid radical cation (ABTS(*+)) and 1,1-diphenyl-2-picrylhydrazyl
      (DPPH(*)) radical scavenging assays. To explore the radioprotective effect of
      umbelliferone, freshly isolated human blood lymphocytes were treated with 124 MUM
      umbelliferone (optimum dose-fixed by MTT assay) 30 min before 3Gy irradiation. It
      was found that umbelliferone pretreatment inhibited radiation-induced reactive
      oxygen species generation in 3Gy exposed lymphocytes. Microscopic observations
      showed that there was a significant apoptotic cells (ethidium bromide/acridine
      orange staining) and decreased mitochondrial membrane potential (Rhodamine 123
      staining) in irradiated lymphocytes. On the other hand, 124 MUM umbelliferone
      treatment significantly decreased % of apoptotic cells and prevented radiation
      induced mitochondrial depolarization in lymphocytes. Further, it was noticed that
      there was an increased DNA damage (comet assay), lipid peroxidation with
      decreased antioxidant enzymatic i.e., superoxide dismutase, catalase and,
      glutathione peroxidase activities in 3Gy irradiated lymphocytes. Conversely,
      umbelliferone (124 MUM) treatment before irradiation decreased comet attributes
      and lipid peroxidative markers with improved antioxidant enzyme activities in
      irradiated lymphocytes. Taken together, the results of this study clearly suggest
      the radioprotective effect of umbelliferone in human lymphocytes by inhibiting
      reactive oxygen species generation and its subsequent toxicity.

PMID- 21946111
TI  - Aliskiren prevents hypertension and reduces asymmetric dimethylarginine in young
      spontaneously hypertensive rats.
AB  - Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NOS, decreases NO
      synthesis. Plasma ADMA concentrations increase markedly in hypertension. We
      tested whether the development of hypertension and the increases in ADMA in
      spontaneously hypertensive rats (SHR) are prevented by aliskiren, a renin
      inhibitor. Male SHRs and normotensive Wistar Kyoto (WKY) control rats, aged 4
      weeks (pre-hypertensive stage), were assigned to 4 groups: untreated SHRs and WKY
      rats, and SHRs that received oral aliskiren 10 and 30 mg/kg/day for 6 weeks. All
      rats were sacrificed at age 10 weeks. Blood pressure decreased at age 6, 8, and
      10 weeks in SHRs that received high-dose aliskiren. Aliskiren mitigated the
      increases in plasma ADMA in SHRs. Renal ADMA levels were lower in SHRs that
      received high-dose aliskiren versus SHRs. SHRs experienced decreased plasma and
      kidney l-Arg-to-ADMA ratios versus control rats, which were reverted by 30 mg/kg
      aliskiren. Renal cortical neuronal NOS-alpha and -beta levels increased in SHRs
      fed with high-dose aliskiren. Early aliskiren treatment mitigates increases in
      ADMA, restores l-Arg-to-ADMA ratios, enhances neuronal NOS-alpha, prevents
      decreased nNOS-beta levels in the kidney-which might restore NO bioavailability
      and contribute to the decrease of blood pressure in young SHRs. Our findings
      suggest that aliskiren is a therapeutic agent for prehypertension that regulates
      the ADMA/NO pathway.

PMID- 21946112
TI  - The role of group I mGlu receptors in the expression of ethanol-induced
      conditioned place preference and ethanol withdrawal seizures in rats.
AB  - In animal models, N-methyl-D-aspartate (NMDA) receptors antagonists inhibit
      physical dependence and the reinforcing effects of ethanol. The group I
      metabotropic glutamate (mGlu) receptors antagonists (mGlu1 and mGlu5) attenuate
      excitatory effect of glutamate by functional modulation of the glutamate/NMDA
      receptors. The objective of the present study was to evaluate the effects of a
      selective mGlu5 receptors antagonist--MTEP, and mGlu1 receptors antagonist-
      EMQMCM, on two processes relevant to alcohol addiction: the expression of ethanol
      induced conditioned place preference (CPP) paradigm, and ethanol withdrawal
      audiogenic seizures in rats. Our experiments indicated that EMQMCM at the doses
      of 5 and 10mg/kg, and MTEP at the doses of 2.5 and 5mg/kg, significantly
      attenuated the expression of ethanol CPP. Furthermore, both group I mGlu receptor
      antagonists, i.e. EMQMCM at the dose of 10mg/kg and MTEP at the dose of 5mg/kg,
      attenuated audiogenic seizures induced by the sound stimulus 12h after withdrawal
      of ethanol in dependent rats. Our study shows the importance of mGlu5 and mGlu1
      receptors for the expression of ethanol-induced CPP and withdrawal seizures,
      although mGlu5 receptors antagonist (MTEP) was more potent than the antagonist of
      mGlu1 receptors (EMQMCM).

PMID- 21946113
TI  - Effect of rasagiline on the molecular composition of the excitatory postsynaptic
      density.
AB  - In the last decade, several neuroprotective therapies have been proposed for
      Parkinson's disease and rasagiline was indicated as one of the most promising
      candidates by preclinical studies. The drug has already been tested in phase III
      clinical studies (the ADAGIO study). The mechanism underlying rasagiline
      dependent neuroprotection is complex and almost unknown. Here, we show that
      rasagiline is involved in the regulation of the molecular composition of the
      postsynaptic density of glutamatergic synapses. In hippocampus as well as in
      striatum, rasagiline induces a significant reduction of synaptic levels of NR2A
      containing NMDA receptors and in hippocampal slices it also significantly
      decreases synaptic levels of GluR1-containing AMPA receptors. This capability of
      rasagiline to modulate ionotropic glutamate receptors composition at synaptic
      sites strengthens the rationale for its clinical use to slow the progression of
      Parkinson's disease.

PMID- 21946114
TI  - Protocatechuic acid promotes the neuronal differentiation and facilitates
      survival of phenotypes differentiated from cultured neural stem and progenitor
      cells.
AB  - Protocatechuic acid (PCA), a phenolic compound isolated from the kernels of
      Alpinia (A.) oxyphylla, plays crucial roles in the proliferation and
      neuroprotection of cultured neural stem and progenitor cells (NS/PCs) in our
      previous study. However, whether PCA modulates the differentiation of NS/PCs has
      remained to be elucidated. In this study, we show that PCA can promote the
      neuronal differentiation combined with fetal bovine serum (FBS) in vitro,
      although it cannot initiate the differentiation of NS/PCs by itself. Moreover,
      PCA is able to induce neuronal maturation and efficiently promote neurite
      outgrowth. On the other hand, PCA facilitates survival of phenotypes
      differentiated from cultured NS/PCs, which was associated with an increased
      percentage of the cellular viability and a decreased percentage of cells
      undergoing apoptosis under differentiation conditions. In addition, PCA-induced
      survival is also mediated with the activating of endogenous antioxidant enzymes.
      These results suggest that PCA may serve as a useful reference for future studies
      in designing stem cell strategies to promote brain recovery and repair in
      neurodegenerative diseases.

PMID- 21946115
TI  - Melanocortin MC4 receptor agonists counteract late inflammatory and apoptotic
      responses and improve neuronal functionality after cerebral ischemia.
AB  - Indirect evidence indicates that, in cerebral ischemia, melanocortins have
      neuroprotective effects likely mediated by MC4 receptors. To gain direct insight
      into the role of melanocortin MC4 receptors in ischemic stroke, we investigated
      the effects of a highly selective MC4 receptor agonist. Gerbils were subjected to
      transient global cerebral ischemia by occluding both common carotid arteries for
      10 min. In saline-treated stroke animals, an impairment in learning and memory
      occurred that, at day 11 after stroke, was associated with hippocampus up
      regulation of tumor necrosis factor-alpha (TNF-alpha), BAX, activated
      extracellular signal-regulated kinases (ERK1/2), c-jun N-terminal kinases
      (JNK1/2) and caspase-3, down-regulation of Bcl-2, and neuronal loss. Treatment
      for 11days with the selective melanocortin MC4 receptor agonist RO27-3225, as
      well as with the well known non-selective [Nle4,D-Phe7]alpha-melanocyte
      stimulating hormone (NDP-alpha-MSH) as a reference non-selective melanocortin,
      counteracted the inflammatory and apoptotic responses, as indicated by the
      changes in TNF-alpha, BAX, ERK1/2, JNK1/2, caspase-3 and Bcl-2 protein
      expression. Furthermore, melanocortin treatment reduced neuronal loss and dose
      dependently improved learning and memory. These positive effects were associated
      with overexpression of Zif268, an immediate early gene involved in injury repair,
      synaptic plasticity and memory formation. Pharmacological blockade of MC4
      receptors with the selective MC4 receptor antagonist HS024 prevented all effects
      of RO27-3225 and NDP-alpha-MSH. These data give direct evidence that stimulation
      of MC4 receptors affords neuroprotection and promotes functional recovery from
      stroke, by counteracting prolonged and/or recurrent inflammatory and apoptotic
      responses, and likely by triggering brain repair pathways.

PMID- 21946116
TI  - In vivo sodium salicylate causes tolerance to acute morphine exposure and alters
      the ability of high frequency stimulation to induce long-term potentiation in
      hippocampus area CA1.
AB  - Effects of morphine on synaptic transmission and plasticity in the hippocampus
      area CA1 following in vivo sodium salicylate and the potential molecular
      mechanism were investigated. Population spikes (PS) were recorded from stratum
      pylamidale of area CA1 following stimulation of Schaffer collaterals in slices
      taken from control and sodium salicylate injected rats. To induce long term
      potentiation (LTP), a 100Hz tetanic stimulation was used. Acute in vitro morphine
      increased baseline PS amplitude in control slices but not in slices taken from
      sodium salicylate treated rats. In vivo chronic salicylate did slightly decrease
      and/or destabilize LTP of CA1 synaptic transmission. We also found that mRNA of
      NR2A subunit of NMDA receptor was reduced in the hippocampus of sodium salicylate
      treated rats as compared to control ones. Following LTP induction, the mRNA of
      NR2A and PP1 (protein phosphatase 1) in slices taken from salicylate-treated rats
      were more than those of control ones. After long-term exposure to in vitro
      morphine, high frequency stimulation (HFS) decreased NR2A mRNA level
      significantly in sodium salicylate treated slices. It is concluded that in vivo
      sodium salicylate causes tolerance to excitatory effect of morphine and changes
      the ability of HFS to induce PS LTP in the hippocampus area CA1 in vitro. These
      changes in synaptic response may be due to alterations in NR2A and PP1
      expression.

PMID- 21946117
TI  - Physical activity and risk of type 2 diabetes among Native Hawaiians, Japanese
      Americans, and Caucasians: the Multiethnic Cohort.
AB  - BACKGROUND: Physical inactivity is an established risk factor for diabetes;
      however, little is known about this association across ethnic groups with
      different diabetes risk. Therefore, we evaluated the association between physical
      activity and diabetes and potential effect modification by ethnicity in the
      Hawaii component of the Multiethnic Cohort. METHODS: Participants, aged 45 to 75
      years, were enrolled by completing a questionnaire on demographics, diet, and
      self-reported weekly hours of strenuous sports, vigorous work, and moderate
      activity. Among the 74,913 participants (39% Caucasian, 14% Native Hawaiian, 47%
      Japanese American), 8561 incident diabetes cases were identified by self-report,
      a medication questionnaire, and through health plan linkages. Cox regression was
      applied to estimate hazard ratios (HR) and 95% confidence intervals (95%CI) while
      adjusting for known confounders. RESULTS: Engaging in strenuous sports was
      inversely related to diabetes risk with HRs (4+ hours/week vs. never) of 0.67
      (95%CI: 0.57-0.79) in women and 0.80 (95%CI: 0.72-0.88) in men. In stratified
      analyses, the inverse association was consistent across ethnic groups. The
      inverse association of vigorous work with diabetes was limited to men, while
      beneficial effects of moderate activity were observed only in Caucasians.
      CONCLUSIONS: These findings support a role of high-intensity physical activity
      and ethnic-specific guidelines in diabetes prevention.

PMID- 21946118
TI  - An interleukin 13 receptor alpha 2-specific peptide homes to human Glioblastoma
      multiforme xenografts.
AB  - Interleukin 13 receptor alpha 2 (IL-13Ralpha2) is a glioblastoma multiforme (GBM)
      associated plasma membrane receptor, a brain tumor of dismal prognosis. Here, we
      isolated peptide ligands for IL-13Ralpha2 with use of a cyclic disulphide
      constrained heptapeptide phages display library and 2 in vitro biopanning schemes
      with GBM cells that do (G26-H2 and SnB19-pcDNA cells) or do not (G26-V2 and SnB19
      asIL-13Ralpha2 cells) over-express IL-13Ralpha2. We identified 3 peptide phages
      that bind to IL-13Ralpha2 in cellular and protein assays. One of the 3 peptide
      phages, termed Pep-1, bound to IL-13Ralpha2 with the highest specificity,
      surprisingly, also in a reducing environment. Pep-1 was thus synthesized and
      further analyzed in both linear and disulphide-constrained forms. The linear
      peptide bound to IL-13Ralpha2 more avidly than did the disulphide-constrained
      form and was efficiently internalized by IL-13Ralpha2-expressing GBM cells. The
      native ligand, IL-13, did not compete for the Pep-1 binding to the receptor and
      vice versa in any of the assays, indicating that the peptide might be binding to
      a site on the receptor different from the native ligand. Furthermore, we
      demonstrated by noninvasive near infrared fluorescence imaging in nude mice that
      Pep-1 binds and homes to both subcutaneous and orthotopic human GBM xenografts
      expressing IL-13Ralpha2 when injected by an intravenous route. Thus, we
      identified a linear heptapeptide specific for the IL-13Ralpha2 that is capable of
      crossing the blood-brain tumor barrier and homing to tumors. Pep-1 can be further
      developed for various applications in cancer and/or inflammatory diseases.

PMID- 21946119
TI  - Heme oxygenase-1 alleviates mouse hepatic failure through suppression of adaptive
      immune responses.
AB  - Heme oxygenase-1 (HO-1) has protective effects on liver damage induced by noxious
      stimuli. The mechanism of action of HO-1 is not well understood. In the present
      study, we investigate the effect of HO-1 in a model of fulminant hepatic failure
      induced by Propionibacterium acnes and lipopolysaccharide (LPS). The expression
      of HO-1 mRNA and protein in the liver was increased after repeated administration
      of the HO-1 inducer cobalt protoporphyrin IX. We found that HO-1 protected mice
      from acute liver damage induced by P. acnes/LPS and prolonged survival. On the
      contrary, administration of the HO-1 inhibitor zinc protoporphyrin IX increased
      liver damage induced by P. acnes/LPS. Subsequently, to investigate the underlying
      mechanisms of HO-1 in the acute liver injury model, we primed mice with P. acnes
      only. We found that the expression of HO-1 mRNA and protein in dendritic cells
      (DCs) was increased after the administration of cobalt protoporphyrin IX. HO-1
      decreased the mature markers major histocompatibility complex II and CD80 on
      liver DCs. The expression of CCR7, CCL2, and CCL22 mRNA, which are expressed by
      mature DCs, was also reduced. These liver DCs could not efficiently stimulate
      CD4+ T cell activation and proliferation. Consequently, HO-1 inhibited the
      activation, proliferation, and T helper 1 polarization of liver-infiltrating CD4+
      T cells and reduced the production of serum alanine aminotransferase and
      proinflammatory cytokines such as interferon-gamma and tumor necrosis factor
      alpha. Taken together, our data suggest that HO-1 alleviates P. acnes/LPS-induced
      fulminant hepatic failure, probably by inhibiting DC-induced adaptive responses.

PMID- 21946120
TI  - Water exchange may be superior to water immersion for colonoscopy.

PMID- 21946121
TI  - Adding triamcinolone to endoscopic ultrasound-guided celiac plexus blockade does
      not reduce pain in patients with chronic pancreatitis.
AB  - BACKGROUND & AIMS: The efficacy of endoscopic ultrasound-guided celiac plexus
      blockade (EUS-CPB) for painful chronic pancreatitis (CP) is uncertain.
      Triamcinolone is often mixed with bupivacaine to lengthen the analgesic effect.
      We investigated whether addition of triamcinolone increases and lengthens pain
      relief compared with EUS-CPB with only bupivacaine. METHODS: We performed a
      single-center, blinded, randomized, controlled trial of 40 adult patients
      referred for EUS-CPB for treatment of painful CP. Patients were assigned randomly
      to groups that received EUS-CPB with triamcinolone and bupivacaine or EUS-CPB
      with only bupivacaine (control). Questionnaires were collected when the study
      began (baseline) and 1 month later. The primary end point was a decrease in the
      pain disability index of 10 or more points at 1 month after the procedure.
      Secondary end points included change in visual analogue scale, narcotic
      requirements, and quality of life at 1 month. RESULTS: There were no significant
      differences in primary outcomes between groups (14.3% for patients who received
      triamcinolone vs 15.8% for controls; P = .64). The trial was stopped for
      futility. There was no significant difference between groups in immediate
      response rates (85.7% for patients who received triamcinolone vs 68.4% for
      control; P = .10), or other secondary end points, including change in pain visual
      analogue scale (0.4 vs 1.0; P = .83), treatment with morphine equivalents at 1
      month (-7.8 vs 0.0; P = .35), change in quality of life at 1 month (SF-12 mental
      component: 1.3 vs -2.1; P = .44; and physical component: -0.2 vs 1.7; P = .54),
      or adverse events. The duration of response was shorter in the triamcinolone
      group (mean, 5.3 vs 0.6 mo; P = .01). CONCLUSIONS: Triamcinolone does not
      increase pain relief or lengthen the effects of EUS-CPB.

PMID- 21946122
TI  - Use of abdominopelvic computed tomography in emergency departments and rates of
      urgent diagnoses in Crohn's disease.
AB  - BACKGROUND & AIMS: In the United States, the use of abdominopelvic computed
      tomography (APCT) by emergency departments for patients with abdominal pain has
      increased, despite stable admission rates and diagnosis requiring urgent
      intervention. We proposed that trends would be similar for patients with Crohn's
      disease (CD). METHODS: We conducted a retrospective study of data from 648 adults
      with CD who presented at 2 emergency departments (2001-2009; 1572 visits). Trends
      in APCT use were assessed with Spearman correlation coefficient. We compared
      patient characteristics and APCT findings during 2001-2003 and 2007-2009.
      RESULTS: APCT use increased from 2001 (used for 47% of encounters) to 2009 (used
      for 78% of encounters; P = .005), whereas admission rates were relatively stable
      at 68% in 2001 and 71% in 2009 (P = .06). The overall proportion of APCTs with
      findings of intestinal perforation, obstruction, or abscess was 29.0%; 34.9% of
      APCTs were associated with urgent diagnoses, including those unrelated to CD.
      Between 2001-2003 and 2007-2009, the proportions of APCTs that detected
      intestinal perforation, obstruction, or abscess were similar (30% vs 29%, P =
      .92), as were the proportions used to detect any diagnosis requiring urgent
      intervention, including those unrelated to CD (36% vs 34%, P = .91). CONCLUSIONS:
      Despite the increased use of APCT by emergency departments for patients with CD,
      there were no significant changes in admission rates between the periods of 2001
      2003 and 2007-2009. The proportion of APCTs that detected intestinal perforation,
      obstruction, abscess, or other urgent conditions not related to CD remained high.

PMID- 21946123
TI  - Immunoglobulin G4 immunostaining of gastric, duodenal, or colonic biopsies is not
      helpful for the diagnosis of autoimmune pancreatitis.
AB  - BACKGROUND & AIMS: The aim of this study was to evaluate the specificity of the
      infiltration of digestive tract mucosa by immunoglobulin (Ig) G4-positive plasma
      cells in patients with autoimmune pancreatitis (AIP), as compared with normal or
      inflammatory mucosa. METHODS: Plasma cell infiltration, CD138 and IgG4
      immunostaining of digestive biopsies were compared in 4 groups of patients: AIP
      type 1 (n = 19); AIP type 2 (n = 4) with inflammatory bowel disease (IBD); IBD
      without pancreatic disorders (n = 20); and controls (n = 26). RESULTS: With AIP
      type 1 versus controls, more plasma cells were present in the gastric mucosa of
      AIP (P = .02) without difference concerning IgG4+ plasma cells at any biopsy
      site. With AIP type 1 versus IBD, colonic mucosa was more often abnormal (P =
      .004), and more CD138 (P = .02) and IgG4 plasma cells (P = .0002) were counted in
      the colon biopsies of IBD. With AIP type 2 versus IBD, no difference for plasma
      cell and IgG4 infiltration was found. CONCLUSIONS: IgG4-positive plasma cells are
      not more numerous in the digestive mucosa of AIP patients than in controls, but
      they are more abundant in the colon of IBD patients than in AIP patients.

PMID- 21946124
TI  - Acute kidney injury is an early predictor of mortality for patients with
      alcoholic hepatitis.
AB  - BACKGROUND & AIMS: Alcoholic hepatitis (AH) is a severe condition with high
      mortality. To improve therapeutic strategies, it is important to identify factors
      that affect survival times. The age, bilirubin, international normalized ratio,
      and creatinine scoring system (also known as the ABIC scoring system) was
      developed previously to determine the prognosis of patients with AH. We studied
      effects of acute kidney injury (AKI) on survival of patients with AH. METHODS: We
      retrospectively analyzed data from 103 patients with biopsy-proven AH. AKI was
      defined as an abrupt reduction (within 48 h) in kidney function that resulted in
      an absolute increase of at least 0.3 mg/dL (or a 50% increase) in serum levels of
      creatinine from baseline (the AKI network [AKIN] criteria). RESULTS: Twenty-nine
      patients (28%) developed AKI during hospitalization, with a median time to
      diagnosis of 3 days. Overall 90-day mortality was 23%, which was significantly
      higher among patients with AKI than those without (65% vs 7%; P < .0001). The
      age, bilirubin, international normalized ratio, and creatinine score (P < .0001)
      and development of AKI (P < .0001) were the most accurate independent predictors
      of 90-day mortality. The presence of systemic inflammatory response syndrome (P <
      .0001), serum bilirubin (P = .01), and international normalized ratio at
      admission (P = .03) were the most accurate predictors of AKI. Importantly, the
      AKIN criteria were more accurate than traditional criteria for renal failure
      (serum creatinine >1.5 mg/dL) in predicting 90-day mortality (area under the
      receiver operating characteristic, 0.83 vs 0.70, respectively; P = .02).
      CONCLUSIONS: Development of AKI reduces survival of patients with AH, in the
      short term. The AKIN criteria are useful and more accurate than traditional
      criteria in predicting mortality. Strategies to prevent AKI therefore should be
      considered in the management of patients with AH.

PMID- 21946125
TI  - A SEER snapshot of anesthesiologist-assisted procedural sedation: in or out of
      focus?

PMID- 21946126
TI  - Construction of a plasmid vector based on the pMV158 replicon for cloning and
      inducible gene expression in Streptococcus pneumoniae.
AB  - We report the construction of a plasmid vector designed for regulated gene
      expression in Streptococcus pneumoniae. The new vector, pLS1ROM, is based on the
      replicon of the streptococcal promiscuous rolling circle replication (RCR)
      plasmid pMV158. We inserted the controllable promoter P(M) of the S.
      pneumoniaemalMP operon, followed by a multi-cloning site sequence aimed to
      facilitate the insertion of target genes. The expression from P(M) is negatively
      regulated by the transcriptional repressor MalR, which is released from the DNA
      operator sequence by growing the cells in maltose-containing media. To get a
      highly regulated expression of the target gene, MalR was provided in cis by
      inserting the malR gene under control of the constitutive P(tet) promoter, which
      in pMV158 directs expression of the tetL gene. To test the functionality of the
      system, we cloned the reporter gene gfp from Aequorea victoria, encoding the
      green fluorescent protein (GFP). Pneumococcal cells harboring the recombinant
      plasmid rendered GFP fluorescence in a maltose-dependent mode with undetectable
      background levels in the absence of the inducer. The new vector, pLS1ROM,
      exhibits full structural and segregational stability and constitutes a valuable
      tool for genetic manipulation and regulated gene expression in S. pneumoniae.

PMID- 21946127
TI  - Celiac disease and autoimmune pancreatitis:  an uncommon association. A case
      report.
AB  - We present the clinical scenario of acute abdominal pain in a 27-year-old man
      with recent-onset type 1 diabetes mellitus. Evaluation of the patient revealed
      elevated levels of serum amylase, lipase, and transaminase without any biliary
      obstruction. He had elevated serum IgG4 levels, and his computed tomography scan
      showed features consistent with autoimmune pancreatitis. Further evaluation
      revealed celiac disease. He was treated as a patient with autoimmune pancreatitis
      and was started on steroids in addition to a gluten-free diet. His liver function
      improved in 6 weeks. He gained weight and his glycemic control also improved.
      Magnetic resonance cholangiopancreatography after 3 months revealed complete
      resolution of pancreatic enlargement. The patient is being followed up in our
      clinic since the past 3 years. To the best of our knowledge and according to the
      Medline search, this is the first case report of celiac disease as an association
      of autoimmune pancreatitis.

PMID- 21946128
TI  - Bringing loyalty to e-Health: theory validation using three internet-delivered
      interventions.
AB  - BACKGROUND: Internet-delivered interventions can effectively change health risk
      behaviors, but the actual use of these interventions by the target group once
      they access the website is often very low (high attrition, low adherence).
      Therefore, it is relevant and necessary to focus on factors related to use of an
      intervention once people arrive at the intervention website. We focused on user
      perceptions resulting in e-loyalty (ie, intention to visit an intervention again
      and to recommend it to others). A background theory for e-loyalty, however, is
      still lacking for Internet-delivered interventions. OBJECTIVE: The objective of
      our study was to propose and validate a conceptual model regarding user
      perceptions and e-loyalty within the field of eHealth. METHODS: We presented at
      random 3 primary prevention interventions aimed at the general public and,
      subsequently, participants completed validated measures regarding user
      perceptions and e-loyalty. Time on each intervention website was assessed by
      means of server registrations. RESULTS: Of the 592 people who were invited to
      participate, 397 initiated the study (response rate: 67%) and 351 (48% female,
      mean age 43 years, varying in educational level) finished the study (retention
      rate: 88%). Internal consistency of all measures was high (Cronbach alpha > .87).
      The findings demonstrate that the user perceptions regarding effectiveness
      (beta(range) .21-.41) and enjoyment (beta(range) .14-.24) both had a positive
      effect on e-loyalty, which was mediated by active trust (beta(range) .27-.60).
      User perceptions and e-loyalty had low correlations with time on the website
      (r(range) .04-.18). CONCLUSIONS: The consistent pattern of findings speaks in
      favor of their robustness and contributes to theory validation regarding e
      loyalty. The importance of a theory-driven solution to a practice-based problem
      (ie, low actual use) needs to be stressed in view of the importance of the
      Internet in terms of intervention development. Longitudinal studies are needed to
      investigate whether people will actually revisit intervention websites and
      whether this leads to changes in health risk behaviors.

PMID- 21946129
TI  - Automatic detection of stent struts with thick neointimal growth in intravascular
      optical coherence tomography image sequences.
AB  - To assist cardiologists investigating neointimal tissue growth on stents during
      follow-up with optical coherence tomography (OCT), we developed an automatic
      algorithm to locate deeply buried stent struts and to quantify the restenosis
      burden. The technique is based on an improved steerable filter for computing the
      local ridge strength and orientation. It also uses an ellipsoid fitting algorithm
      and continuity criteria to obtain globally optimal stent localization. The
      restenosis burden calculations were compared to manual assessment of OCT coronary
      artery image data obtained from in vivo human clinical studies. Compared to
      manual assessment by expert readers, the algorithm operated with > 97% accuracy
      in the measurement of mean and maximum restenosis burden. The results indicated
      that the technique yielded comparable accuracy in measuring restenosis burden,
      and significantly reduced user interaction time.

PMID- 21946130
TI  - Resveratrol and its impact on aging and thyroid function.
AB  - Resveratrol, the naturally occurring polyphenolic compound characterized by anti
      oxidative, anti-inflammatory and apoptotic properties, appears to contribute
      substantially to cardioprotection and cancer-prevention. In addition, resveratrol
      is believed to regulate several biological processes, mainly metabolism and
      aging, by modulating the mammalian silent information regulator 1 (SIRT1) of the
      sirtuin family. Resveratrol may arrest, among various tumors, cell growth in both
      papillary and follicular thyroid cancer by activation of the mitogen-activated
      protein kinase (MAPK) signal transduction pathway as well as increase of p53 and
      its phosphorylation. Finally, resveratrol also influences thyroid function by
      enhancing iodide trapping and, by increasing TSH secretion via activation of
      sirtuins and the phosphatidylinositol- 4-phosphate 5 kinase gamma (PIP5Kgamma)
      pathway, positively affects metabolism.

PMID- 21946131
TI  - [Algorithm identification of differential diagnostic clinical syndromes in
      patients with neuroepithelial tumors of the III ventricle].
AB  - An algorithm for identifying differential diagnostic clinical syndromes in
      neurooncologic patients was suggested. This technique involves: creating a
      database of cases - lists of symptoms, requests for selection of thematic cases
      with their subsequent division into the main and control groups; generation of
      single-symptom applicants; selection and verification of clinical differential
      diagnostic syndromes appropriate to sensitivity and specificity using a 4-dipole
      table and selection of the best of them. Based on the database of 368 patients
      with tumors of basal-diencephalic localization, we tried to perform the algorithm
      of identification of differential diagnostic clinical syndromes in patients with
      different anatomical and topographical variations of neuroepithelial tumors of
      the III ventricle. The identified syndromes are reasonable to use for selecting
      the optimal treatment strategy.

PMID- 21946132
TI  - [The effect of abnormal interests on social ability of mentally ill children and
      adolescents].
AB  - Authors have studied 62 patients, aged 4-16 years old, who were admitted to the
      Moscow Children's Psychiatric Hospital No6. Patients had the following types of
      pathological interests depending on their context: intellectual interests,
      creative modeling, passionate, animalistic and cult. Three clinical variants of
      pathological interests depending on their structure have been singled out:
      "narrow", "overvalued" and "overvalued-delusional". These variants differed by
      the frequency and severity of basic components: affective, ideatory, specific
      activity drive. The distinct social-maladaptation effect of abnormal interests in
      children and adolescents was found. Its intensity depended on above-mentioned
      variants. Narrow abnormal interests defined moderate social disability which was
      revealed in the family circle. Overvalued interests were characterized by a
      considerable disability which included disorders of both family and school life.
      Overvalued-delusional interests predetermined severe disability of children and
      adolescent.

PMID- 21946133
TI  - [Modern aspects of the rehabilitation of patients with epilepsy].
AB  - A conception of rehabilitation of epileptic patients, which corresponds to the
      realities of their life, has been elaborated on the basis of clinical data on
      4348 epileptic patients with long-time follow-up period. An algorithm of
      treatment and rehabilitation programs based on medical-biopsychosocial approaches
      and studying of QOL was proposed and scientifically substantiated. The system of
      rehabilitation was tested in practice and its high efficacy was shown.

PMID- 21946134
TI  - [Reflexotherapy combined with cortexin in the complex treatment of speech
      disorders in patients with cerebral palsy].
AB  - Authors studied 78 outpatients with children cerebral palsy, aged from 2 to 7
      years, in the children department of neurology and reflexotherapy. All children
      had speech disorders of different severity: from a severe mental-speech deficit
      to muscle asinergia of the speech apparatus. Combined microcurrent reflexotherapy
      (MCRT) in the author's technique and the neuroprotector cortexin were used for
      treatment. The main group included 40 patients who received the treatment of MCRT
      in the combination with cortexin, the comparison group consisted of 38 patients
      who received only MCRT. MCRT consisted of 15 sessions with one month interval
      after the first treatment and two months after the second one. The treatment with
      cortexin included sessions of 10 injections each after the end of the first and
      the third MCRT sessions. Patient state was measured at baseline and at the end of
      6 month treatment program. An analysis of results of the complex treatment
      demonstrated its high efficacy in the recovery of speech functions in children
      with cerebral palsy compared to patients of the comparison group.

PMID- 21946135
TI  - [The profile of adult patients with upper limb muscle spasticity treated with
      botulinum toxin type A (an international survey)].

PMID- 21946136
TI  - [Evoked potentials and brainstem reflex activity in patients of young and middle
      age with chronic headache].
AB  - Neurophysiological peculiarities of functional state of afferent systems,
      including brain evoked potentials of different modalities and brainstem reflex
      activity, in patients of young and middle age with chronic headaches have been
      studied. In young patients, there was the increased reflex activity of visual and
      trigeminal systems, somatosensory cortex and brainstem structures that indicated
      the main role of the generator of pathologically increased excitation (GPIE) of
      different levels in the pathogenesis of chronic pain. In patients of middle age,
      we observed the predominant role of conduction delay on the supraspinal level.
      The revealed age-related neurophysiological peculiarities determine the
      pathogenetic therapy of chronic headaches.

PMID- 21946137
TI  - [Diurnal changes of alpha-rhythm in endogenous depressions].
AB  - The aim of the study was to find the diurnal changes in the EEG alpha-activity in
      patients with endogenous depressions. Both morning and evening EEG records were
      characterized by the transition of modal value of leading rhythm into the lower
      frequency band (9-10 Hz versus 10-11 Hz in healthy people). The spectral power of
      alpha-rhythm was higher, especially in the occipital cortical areas, in the
      morning hours than in the evening. In the morning, the intrahemispheric
      differences in the alpha-rhythm power in occipital areas were leveled out while
      in the evening hours, the normalization of intrahemispheric balance with higher
      power of alpha-rhythm in the right occipital area was seen. A comparative
      analysis of mean values of coherence (COH) in cortical areas in patients revealed
      higher COH values in parietal-central areas of both hemispheres, as well as in
      frontal- and right middle temporal areas, in the morning compared to those in the
      evening. COH values were lower in the morning than in the evening in occipital
      and posterior temporal areas. The mean COH value of alpha-rhythm in the right
      hemisphere was higher compared to the left hemisphere both in the morning and in
      the evening.

PMID- 21946138
TI  - [Clinical significance of humoral compensatory reactions in the acute period of
      ischemic stroke].
AB  - To determine the clinical significance of humoral nonspecific reactions in the
      acute period of ischemic hemispheric stroke (IS), some biochemical and
      biophysical parameters have been studied in 30 patients (mean age 67+/-10 years).
      Platelet monoaminooxidase (MAO) activity, levels of middle-sized molecules (MM),
      malonic dialdehyde (MDA) and parameters of the functional state of serum albumin
      (the effective concentration and binding reserve of albumin) have been measured.
      Severity of neurological deficit and functional recovery of patients with IS was
      assessed with the NIHSS and the Barthel index. The control group included 17 age-
      and sex-matched healthy people (p<0,1). The significant changes in all
      biochemical and biophysical parameters were seen in patients compared to the
      control group (p<0,01). The increase in MAO activity in patients was associated
      with the enhancement of free-radical reactions MDA/MAO: rs=+0,62, p=0,0001. The
      elevation of acceptor capacity of albumin related to the enhancement of its
      detoxicating function was found in patients with the regression of neurological
      deficit. It has been assumed that some nonspecific humoral reactions play a
      pathogenetic role in the acute period of ischemic stroke.

PMID- 21946140
TI  - [Age as a risk factor for cognitive impairment after coronary artery by-pass
      surgery].

PMID- 21946139
TI  - [Innate and adaptive immunity in children with psychotic forms of autism-spectrum
      disorders].
AB  - Leukocyte elastase (LE) activity, functional activity of alpha1-proteinase
      inhibitor, C-reactive protein, autoantibodies to nerve growth factor and to basic
      myelin protein have been studied in the blood serum of children with psychotic
      forms of autistic disorders - children psychosis (F84.02) and atypical children
      psychosis (F84.11). The activation of innate immunity (the increase in LE
      activity and acute phase proteins) was seen in children psychosis. The more
      severe mental disturbances, that are characteristic of endogenous atypical
      children psychosis, were accompanied by the activation of both innate and
      adaptive immunity ( the increase of the level of autoantibodies to neuroantigenes
      in the peripheral blood). Correlations between immunological and clinical
      parameters suggest the involvement of innate and adaptive immunity in the
      formation of autistic and cognitive disorders in children.

PMID- 21946141
TI  - [Correlations of quality of life with anxiety and depression in patients with
      vertigo].

PMID- 21946142
TI  - [Clinical-immunological aspects of multiple sclerosis treatment with
      ethylmethylhydroxypyridine succinate].

PMID- 21946143
TI  - [The efficiency of aceclofenac in acute vertebrogenic compression-ischemic
      syndrome].

PMID- 21946144
TI  - [Pharmacotherapy of basic clinical presentations of chronic brain ischemia].

PMID- 21946145
TI  - [Quality of life of patients with ischemic stroke during non-pharmacological
      rehabilitation].

PMID- 21946146
TI  - [Multifocal motor neuropathy without conduction blocks and antibodies to GM1
      gangliosides].

PMID- 21946147
TI  - Developing scales to assess parental instrumental social support and influence on
      provision of social support for physical activity in children.
AB  - BACKGROUND: An important influence on youth physical activity (PA) is the
      provision of instrumental social support (ISS) by parents and other adults.
      Limited research exists about factors that influence parental provision of ISS
      for youth PA. Following a theory-based conceptual model, a measure for assessing
      ISS for PA was developed from elicitation survey results. The purpose of this
      paper is to describe elicitation methodology and ISS instrument development.
      METHODS: Parents (N = 37) of children (5-14 years) responded to open-ended
      questions assessing modal beliefs about their provision of ISS for PA regarding
      a) positive/negative beliefs, b) normative beliefs, c) self-efficacy (SE), and d)
      ISS for PA. Data were analyzed qualitatively. RESULTS: ISS behaviors reported by
      parents include enroll/sign-up youth for structured PA, paying expenses for
      participation in structured/unstructured PA, and providing transportation for
      unstructured/structured PA. Child health and fitness (benefits), and
      time/scheduling conflicts (barriers) were most frequently reported behavioral
      beliefs. Family members were most frequently identified as specific referents for
      normative beliefs. Final instrument scales yielded moderately high internal
      consistency reliability scores. CONCLUSIONS: When developing scales not
      previously assessed in a population, eliciting modal beliefs about a behavior is
      an important formative step in instrument development.

PMID- 21946149
TI  - Adiponectin reduces connective tissue growth factor in human hepatocytes which is
      already induced in non-fibrotic non-alcoholic steatohepatitis.
AB  - Connective tissue growth factor (CTGF) is induced in liver fibrosis and enhances
      the activity of transforming growth factor beta (TGFbeta). Recently we have shown
      that the hepatoprotective adipokine adiponectin downregulates CTGF in primary
      human hepatocytes (PHH). In the current study, the mechanisms mediating
      suppression of CTGF by adiponectin and the well described downstream effector of
      adiponectin receptor 2 (AdipoR2), peroxisome proliferator activated receptor
      alpha (PPARalpha), were analyzed in more detail. Adiponectin downregulated CTGF
      mRNA and protein in primary human hepatocytes (PHH) and suppression was blocked
      by a PPARalpha antagonist indicating that AdipoR2 is involved. The PPARalpha
      agonists fenofibrate and WY14643 also reduced CTGF protein in these cells.
      Adiponectin further impaired TGFbeta-mediated upregulation of CTGF.
      Phosphorylation of the TGFbeta downstream effectors SMAD2 and -3 was reduced in
      PHH incubated with adiponectin or PPARalpha agonists suggesting that early steps
      in TGFbeta signal transduction are impaired. CTGF and TGFbeta mRNA levels were
      increased in human non-fibrotic non-alcoholic steatohepatitis (NASH), and here
      AdipoR2 expression was significantly reduced. Current data show that CTGF and
      TGFbeta are already induced in non-fibrotic NASH and this may be partly explained
      by low adiponectin bioactivity which interferes with TGFbeta signaling by
      reducing phosphorylation of SMAD2/3 and by downregulating CTGF.

PMID- 21946148
TI  - Characterization of specificity of bacterial community structure within the
      burrow environment of the marine polychaete Hediste (Nereis) diversicolor.
AB  - Bioturbation is known to stimulate microbial communities, especially in
      macrofaunal burrows where the abundance and activities of bacteria are increased.
      Until now, these microbial communities have been poorly characterized and an
      important ecological question remains: do burrow walls harbor similar or specific
      communities compared with anoxic and surface sediments? The bacterial community
      structure of coastal sediments inhabited by the polychaete worm Hediste
      diversicolor was investigated. Surface, burrow wall and anoxic sediments were
      collected at the Carteau beach (Gulf of Fos, Mediterranean Sea). Bacterial
      diversity was determined by analyzing small subunit ribosomal RNA (16S rRNA)
      sequences from three clone libraries (168, 179 and 129 sequences for the surface,
      burrow wall and anoxic sediments, respectively). Libraries revealed 306 different
      operational taxonomic units (OTUs) belonging to at least 15 bacterial phyla.
      Bioinformatic analyses and comparisons between the three clone libraries showed
      that the burrow walls harbored a specific bacterial community structure which
      differed from the surface and anoxic environments. More similarities were
      nevertheless found with the surface assemblage. Inside the burrow walls, the
      bacterial community was characterized by high biodiversity, which probably
      results from the biogeochemical heterogeneity of the burrow system.

PMID- 21946150
TI  - Rewarding electrical brain stimulation in rats after peripheral nerve injury:
      decreased facilitation by commonly abused prescription opioids.
AB  - BACKGROUND: Prescription opioid abuse is a significant concern in treating
      chronic pain, yet few studies examine how neuropathic pain alters the abuse
      liability of commonly abused prescription opioids. METHODS: Normal and spinal
      nerve ligated (SNL) rats were implanted with electrodes into the left ventral
      tegmental area (VTA). Rats were trained to lever press for intracranial
      electrical stimulation (VTA ICSS), and the effects of methadone, fentanyl,
      hydromorphone, and oxycodone on facilitation of VTA ICSS were assessed. A second
      group of neuropathic rats were implanted with intrathecal catheters, and the
      effects of intrathecal clonidine, adenosine, and gabapentin on facilitation of
      VTA ICSS were assessed. The effects of electrical stimulation of the VTA on
      mechanical allodynia were assessed in SNL rats. RESULTS: Responding for VTA ICSS
      was similar in control and SNL rats. Methadone, fentanyl, and hydromorphone were
      less potent in facilitating VTA ICSS in SNL rats. Oxycodone produced a
      significant facilitation of VTA ICSS in control (maximum shift 24.10 +/- 6.19 Hz)
      but not SNL rats (maximum shift 16.32 +/- 7.49 Hz), but also reduced maximal
      response rates in SNL rats. Intrathecal administration of clonidine, adenosine,
      and gabapentin failed to facilitate VTA ICSS in SNL rats, and electrical
      stimulation of the VTA did not alter mechanical allodynia following nerve injury.
      CONCLUSIONS: The present data suggests that the positive reinforcing effects of
      commonly abused prescription opioids are diminished following nerve injury. In
      addition, alleviation of mechanical allodynia with nonopioid analgesics does not
      appear to stimulate limbic dopamine pathways originating from the VTA in SNL
      rats.

PMID- 21946152
TI  - The need and benefit of augmented feedback on service speed in tennis.
AB  - PURPOSE: Accurate knowledge of results (KR), in the form of service speed, is
      important in learning to serve faster. The aim was to determine whether players
      could accurately judge if their serve was faster or slower than their preceding
      serve (experiment 1) and if providing them with accurate augmented KR feedback on
      service speed using a speed gun could enhance learning after training (experiment
      2). METHODS: In experiment 1, 11 high-level national junior players served 10
      serves to a target area and were asked to judge whether the serve was
      faster/slower that the preceding serve. In experiment 2, 12 high-level national
      junior players, divided into two groups, trained to improve their service speed
      for 12 wk (three sessions per week). During the first 6 wk (90 maximum-effort
      serves/session), they received either augmented (group 1) or no augmented (group
      2) KR feedback. During the following 6 wk, participants did not complete the 90
      serves per session and received no augmented KR feedback (retention test).
      RESULTS: In experiment 1, players could not correctly determine whether serves
      were faster/slower than the preceding serve. In experiment 2, both groups
      significantly enhanced their service speed after the initial 6 wk of service
      training, but the enhancement was significantly greater (P = 0.01) in the
      augmented versus no augmented KR feedback group (0.84 +/- 0.38 vs 0.22 +/- 0.04
      m.s-1 ). These enhancements were still evident during the retention test (P =
      0.01). CONCLUSIONS: Players cannot accurately judge service speed, and by
      providing this information in the form of augmented feedback, a player can
      enhance the process of learning to serve faster with training. Players should
      therefore use augmented feedback on service speed when training to serve faster.

PMID- 21946151
TI  - TASK Channel Deletion Reduces Sensitivity to Local Anesthetic-induced Seizures.
AB  - BACKGROUND: Local anesthetics (LAs) are typically used for regional anesthesia
      but can be given systemically to mitigate postoperative pain, supplement general
      anesthesia, or prevent cardiac arrhythmias. However, systemic application or
      inadvertent intravenous injection can be associated with substantial toxicity,
      including seizure induction. The molecular basis for this toxic action remains
      unclear. METHODS: We characterized inhibition by different LAs of homomeric and
      heteromeric K channels containing TASK-1 (K2P3.1, KCNK3) and TASK-3 (K2P9.1,
      KCNK9) subunits in a mammalian expression system. In addition, we used TASK
      1/TASK-3 knockout mice to test the possibility that TASK channels contribute to
      LA-evoked seizures. RESULTS: LAs inhibited homomeric and heteromeric TASK
      channels in a range relevant for seizure induction; channels containing TASK-1
      subunits were most sensitive and IC50 values indicated a rank order potency of
      bupivacaine > ropivacaine >> lidocaine. LAs induced tonic-clonic seizures in mice
      with the same rank order potency, but higher LA doses were required to evoke
      seizures in TASK knockout mice. For bupivacaine, which produced the longest
      seizure times, seizure duration was significantly shorter in TASK knockout mice;
      bupivacaine-induced seizures were associated with an increase in
      electroencephalogram power at frequencies less than 5 Hz in both wild-type and
      TASK knockout mice. CONCLUSIONS: These data suggest that increased neuronal
      excitability associated with TASK channel inhibition by LAs contributes to
      seizure induction. Because all LAs were capable of evoking seizures in TASK
      channel deleted mice, albeit at higher doses, the results imply that other
      molecular targets must also be involved in this toxic action.

PMID- 21946153
TI  - Androgens affect myogenesis in vitro and increase local IGF-1 expression.
AB  - PURPOSE: The mechanism whereby anabolic androgens are associated with hypertrophy
      of skeletal muscle is incompletely understood but may involve an interaction with
      locally generated insulin-like growth factor (IGF) 1. The present investigation
      utilized a cell culture model of human skeletal muscle-derived cell maturation to
      test the hypothesis that androgens increase differentiation of human muscle
      precursor cells in vitro and to assess effects of androgen with or without IGF-1
      on IGF-1 messenger RNA (mRNA) expression in human muscle precursor cells.
      METHODS: Differentiation of muscle-derived cells was induced under standard low
      serum conditions. Cultures were then exposed to androgen (testosterone (T)) at
      50, 100, and 500 nM or IGF-1 (10-50 ng.mL-1). Immunocytochemistry and real-time
      polymerase chain reaction (RT-PCR) were used to assess effects of androgens and
      IGF-1 after 3- (early) or 7-d (late) muscle differentiation, respectively; RT-PCR
      was used to quantify the effects on androgen receptor expression. RESULTS: Under
      low-serum conditions, 3-d exposure to androgens or IGF-1 or both resulted in no
      significant increase in cellular myogenic commitment. After 7-d exposure,
      however, T and IGF-1 were both found to increase fusion index with no observable
      synergistic effect. T also increased IGF-1 mRNA generation (P < 0.0001), whereas
      exogenous IGF-1 (P < 0.001) reduced IGF-1 mRNA transcription relative to control.
      The T effect was reversible after treatment with flutamide, an androgen receptor
      antagonist. CONCLUSIONS: Both T and IGF-1 increase myogenic commitment after 7-d
      exposure to a differentiation medium. With T causing a concomitant increase in
      IGF-1 mRNA underpinning IGF-1 as a central mediator in the cellular pathways
      associated with muscle hypertrophy, including those affected by androgens. The
      novel system described has the potential for elucidating the pattern of growth
      factor effects associated with androgens in skeletal muscle.

PMID- 21946154
TI  - No effect of protein coingestion on exogenous glucose oxidation during exercise.
AB  - PURPOSE: We examined the hypothesis that protein coingestion with glucose during
      endurance exercise increases exogenous glucose oxidation rate and gut comfort and
      lowers perceived exertion. METHODS: In a randomized crossover design, eight male
      cyclists rode 150 min at 50% of peak power on three occasions while ingesting
      solutions containing the following: 8% 13C-enriched glucose and 2% milk protein
      concentrate (protein-glucose), glucose only (glucose), or noncaloric placebo
      (water). All solutions contained sodium citrate ([+Na] 60 mmol.L-1) and flavor
      and were ingested at 150 mL.15 min-1. The exogenous carbohydrate oxidation rate
      was determined using stable isotope method and indirect calorimetry. RESULTS:
      Protein coingestion had no effect on the exogenous glucose oxidation rate but
      increased endogenous carbohydrate oxidation rate (16%; 90% confidence limits +/
      7%), relative to glucose. Total carbohydrate and fat oxidation rates were
      increased (25%; +/-6%) and decreased (17%; +/-4%), respectively, by protein
      coingestion relative to water, but the effect relative to glucose was trivial.
      The plasma glucose concentration relative to glucose (mean +/- SD; 6.1 +/- 0.8
      mmol.L-1) was 5.8% (+/-3%) lower with protein coingestion; there were no clear
      differences in glucose concentration for the remaining comparisons or for lactate
      concentration. Perceived exertion was not altered by protein coingestion;
      however, there was a small decrease in nausea with the protein-glucose solution
      relative to water (-0.14 +/- 0.08 U); other protein-affected comparisons were
      without note. CONCLUSIONS: Adding protein to a glucose-sodium solution ingested
      during exercise had neutral effect on exogenous carbohydrate oxidation and
      perception and little effect on metabolic measures associated with endurance
      performance. We conclude that previously reported effects of protein coingestion
      on endurance capacity were unlikely due to increased exogenous carbohydrate
      provision.

PMID- 21946155
TI  - A simplified approach for the estimation of the ventilatory compensation point.
AB  - Incremental cardiopulmonary exercise test with gas exchange measurement is the
      gold standard for the identification of the ventilatory compensation point (VCP).
      It has previously been demonstrated that the change in the slope of increment of
      minute ventilation over HR (DeltaVE/DeltaHR) can be used alternatively to the
      ventilatory equivalent for CO2 (VE/VCO2) method for detection of VCP in healthy
      subjects undergoing cycle ergometer (C) incremental exercise. The same evaluation
      during treadmill (T) incremental exercise and comparison between C and T have not
      yet been performed. PURPOSE: We analyzed, during both C and T incremental
      exercises, the VE/HR and the respiratory rate (RR)/HR relationships, expressed
      either as slope or as an absolute value. We hypothesized that changes in the
      slope of increment of the two relationships could represent a reliable method for
      VCP detection, regardless of exercise mode and protocol. METHODS: Fourteen
      healthy male subjects (age = 31 +/- 7 yr (mean +/- SD)) underwent two T
      incremental exercises--fast (FT) and slow (ST) protocols (8 km.h-1, 2% (F(T)) and
      1% (S(T)) grade per minute)--and one C incremental exercise (30 W.min-1). O2
      uptake (VO2), VCO2, VE, HR, and RR were measured breath by breath. RESULTS: A
      good between-method agreement in the detection of VCP by the DeltaV(E)/DeltaVCO2,
      DeltaV(E)/DeltaHR, and the DeltaRR/DeltaHR slope changes was found in both T
      protocols and C. No differences (C vs T and F(T) vs S(T)) were found in the slope
      of the DeltaV(E)/DeltaHR and DeltaRR/DeltaHR relationships after the VCP and in
      the V(E)/HR and RR/HR absolute values at VCP. CONCLUSIONS: In healthy young
      males, the DeltaVE/DeltaHR and DeltaRR/DeltaHR relationships during T and C
      incremental exercises can be reliably used to detect the VCP as an alternative to
      the ventilatory equivalent method.

PMID- 21946156
TI  - Neighborhood environment and psychosocial correlates of adults' physical
      activity.
AB  - BACKGROUND: There is growing interest in identifying neighborhood environment
      factors related to physical activity. PURPOSE: This study aimed to examine
      whether objective built (e.g., residential density) and perceived (e.g.,
      aesthetics) environment factors around adults' residence are correlates of their
      physical activity and reported walking behavior after accounting for known
      psychosocial (e.g., self-efficacy, barriers to physical activity) and demographic
      correlates of physical activity. METHODS: Objective built environment
      characteristics were created through network buffers around individual
      participants (n = 2199) selected from neighborhoods differing on walkability
      characteristics and household income. Participants wore accelerometers to obtain
      a more objective measure of overall physical activity and self-reported on
      leisure and transportation-related walking, perceptions of neighborhood
      environment, psychosocial factors related to physical activity, and demographic
      factors. Census-level demographic factors were also considered. RESULTS: Retail
      floor area ratio, a metric combining land use mix and pedestrian design factors,
      was the environmental factor most related to accelerometry-measured physical
      activity and self-reported transportation-related walking after accounting for
      psychosocial and demographic factors. Street connectivity was also related to
      transportation-related walking, whereas perceived aesthetics was positively
      related to leisure walking. CONCLUSIONS: Environmental factors, particularly the
      availability of proximal nonresidential destinations designed for pedestrian
      access, were related to adults' physical activity and walking after accounting
      for psychosocial and demographic correlates, including reasons for residential
      selection.

PMID- 21946157
TI  - Development of the Rural Active Living Perceived Environmental Support Scale
      (RALPESS).
AB  - BACKGROUND: Evidence supports the role of physical and social environments in
      active living, including perception of environment. However, measurement of
      perceived environments in rural settings is lacking. This study describes the
      development of the Rural Active Living Perceived Environmental Support Scale
      (RALPESS). METHODS: Premised on social ecological and cognitive perspectives, 85
      initial items were generated through a literature review and a mixed-methods
      investigation of "activity-friendly" environments. Items were organized by
      resource areas--town center, indoor and outdoor physical activity areas, schools,
      churches, and areas around the home/neighborhood--and submitted for expert panel
      review. In 2009, a revised questionnaire was disseminated to adolescents,
      parents, public school staff, and older adults in 2 rural southeastern United
      States counties. Principal component analysis with varimax rotation was used to
      explore factor structure (n = 542). RESULTS: The final analysis yielded 33 items
      with 7 factors: 1) church facilities, 2) town center connectivity, 3) indoor
      areas, 4) around the home/neighborhood, 5) town center physical activity
      resources, 6) school grounds, and 7) outdoor areas. CONCLUSIONS: The RALPESS is a
      valid, internally consistent, and practically useful instrument to measure
      perceptions of rural environments in the context of physical activity across the
      lifespan. Confirmatory factor analysis is recommended to validate factor
      structure.

PMID- 21946158
TI  - Periodontal disease is associated with higher levels of C-reactive protein in non
      diabetic, non-smoking acute myocardial infarction patients.
AB  - OBJECTIVES: A link between periodontal disease (PD) and cardiovascular events has
      been proposed, but confounding by shared risk factors such as smoking and
      diabetes remains a concern. We examined the prevalence of PD and its contribution
      to C-reactive protein (CRP) levels in acute myocardial infarction (AMI) patients
      and in subjects without AMI and with angiographically nonobstructive coronary
      disease in the absence of these confounding risk factors. METHODS: Periodontal
      status and admission CRP levels were evaluated in 87 non-diabetic and non-smoking
      subjects undergoing cardiac catheterization. The study group comprised of 47
      patients with documented AMI, and 40 subjects without AMI and with
      angiographically nonobstructive coronary disease (ANCD group). RESULTS: Both the
      prevalence of PD and CRP levels were significantly higher in AMI patients
      compared with ANCD subjects (38.3% vs. 17.5%, p=0.03 and 44.3 vs. 8.5 mg/L,
      p<0.001 respectively). PD was associated with higher CRP levels in AMI patients
      (52.5 vs. 36.1 mg/L, p=0.04) as well as in ANCD subjects, however, in this group
      this was not significant (12.6 vs. 7.6 mg/L, p=0.5). Multivariable regression
      analysis confirmed two separate measures of PD as strong and independent
      contributors to elevated CRP levels in AMI patients (R2 = 0.28, R2 = 0.30,
      p=0.001). CONCLUSIONS: PD contributes to elevated CRP levels in non-diabetic, non
      smoking AMI patients, independently of other confounding factors. These findings
      imply that periodontitis may emerge as a novel target for reducing future risk in
      AMI survivors.

PMID- 21946159
TI  - Applications of genetically-encoded biosensors for the construction and control
      of biosynthetic pathways.
AB  - Cells are filled with biosensors, molecular systems that measure the state of the
      cell and respond by regulating host processes. In much the same way that an
      engineer would monitor a chemical reactor, the cell uses these sensors to monitor
      changing intracellular environments and produce consistent behavior despite the
      variable environment. While natural systems derive a clear benefit from pathway
      regulation, past research efforts in engineering cellular metabolism have focused
      on introducing new pathways and removing existing pathway regulation. Synthetic
      biology is a rapidly growing field that focuses on the development of new tools
      that support the design, construction, and optimization of biological systems.
      Recent advances have been made in the design of genetically-encoded biosensors
      and the application of this class of molecular tools for optimizing and
      regulating heterologous pathways. Biosensors to cellular metabolites can be taken
      directly from natural systems, engineered from natural sensors, or constructed
      entirely in vitro. When linked to reporters, such as antibiotic resistance
      markers, these metabolite sensors can be used to report on pathway productivity,
      allowing high-throughput screening for pathway optimization. Future directions
      will focus on the application of biosensors to introduce feedback control into
      metabolic pathways, providing dynamic control strategies to increase the
      efficient use of cellular resources and pathway reliability.

PMID- 21946160
TI  - Spatial organization of enzymes for metabolic engineering.
AB  - As synthetic pathways built from exogenous enzymes become more complicated, the
      probability of encountering undesired interactions with host organisms increases,
      thereby lowering product titer. An emerging strategy to combat this problem is to
      spatially organize pathway enzymes into multi-protein complexes, where high local
      concentrations of enzymes and metabolites may enhance flux and limit problematic
      interactions with the cellular milieu. Co-localizing enzymes using synthetic
      scaffolds has improved titers for multiple pathways. While lacking physical
      diffusion barriers, scaffolded systems could concentrate intermediates locally
      through a mechanism analogous to naturally occurring microdomains. A more direct
      strategy for compartmentalizing pathway components would be to encapsulate them
      within protein shells. Several classes of shells have been loaded with exogenous
      proteins and expressed successfully in industrial hosts. A critical challenge for
      achieving ideal pathway compartmentalization with protein shells will likely be
      evolving pores to selectively limit intermediate diffusion. Eventually, these
      tools should enhance our ability to rationally design metabolic pathways.

PMID- 21946162
TI  - Should we be using kidneys from hepatitis C virus-infected donors?
AB  - PURPOSE OF REVIEW: Transplantation of kidneys from donors with a positive
      serology for hepatitis C virus (HCVD positive) remains controversial. RECENT
      FINDINGS: Registry studies reported that the use of HCVD positive kidneys into
      HCV positive recipients is associated with shorter time awaiting transplantation
      but with a small increase in hazard for death and graft loss compared with HCVD
      negative. Notably, patients who received kidneys from HCVD positive have better
      survival than those who remain in the waitlist. A collaborative study using HCVD
      positive kidneys into HCVRNA positive recipients showed that HCV serology was not
      an independent risk factor for liver disease, graft survival, and patient
      survival in the long term. The safety of this approach can be improved by
      matching donors and recipients according to HCV genotypes. Because the incidence
      and prevalence of HCV infection in dialysis patients are decreasing, kidneys from
      HCVD positive are becoming surplus organs due to the lack of appropriate
      recipients in the waitlist. To improve the underutilization of these kidneys,
      organizational measures, including the offer of these kidneys for preemptive
      transplantation, are suggested. SUMMARY: The use of kidneys from HCVD positive
      into HCVR positive seems to be a safe approach in the long term, showing a better
      patient survival than that of HCV positive patients on the waitlist.

PMID- 21946161
TI  - Cell-free synthetic biology: thinking outside the cell.
AB  - Cell-free synthetic biology is emerging as a powerful approach aimed to
      understand, harness, and expand the capabilities of natural biological systems
      without using intact cells. Cell-free systems bypass cell walls and remove
      genetic regulation to enable direct access to the inner workings of the cell. The
      unprecedented level of control and freedom of design, relative to in vivo
      systems, has inspired the rapid development of engineering foundations for cell
      free systems in recent years. These efforts have led to programmed circuits,
      spatially organized pathways, co-activated catalytic ensembles, rational
      optimization of synthetic multi-enzyme pathways, and linear scalability from the
      micro-liter to the 100-liter scale. It is now clear that cell-free systems offer
      a versatile test-bed for understanding why nature's designs work the way they do
      and also for enabling biosynthetic routes to novel chemicals, sustainable fuels,
      and new classes of tunable materials. While challenges remain, the emergence of
      cell-free systems is poised to open the way to novel products that until now have
      been impractical, if not impossible, to produce by other means.

PMID- 21946163
TI  - Managing patients with a failed kidney transplant:  how can we do better?
AB  - PURPOSE OF REVIEW: Patients with a failed kidney transplant represent a unique
      chronic kidney disease (CKD) population that is increasing in number, and that is
      at high risk of morbidity and mortality because of a prolonged history of CKD
      that may be sub-optimally managed, and exposure to immunosuppressant medications
      that are often continued after transplant failure. RECENT FINDINGS: There is no
      consensus on the optimal use of immunosuppressant medications after transplant
      failure. Recent observational studies have demonstrated that surgical removal of
      the failed allograft and discontinuation of immunosuppressant medications may be
      associated with a decreased long-term risk of mortality. However, the indications
      for elective transplant nephrectomy remain poorly defined. Removal of the failed
      allograft may limit opportunities for repeat transplantation by increasing
      cytotoxic antibody levels, and may be associated with an increased risk of repeat
      transplant failure. SUMMARY: In the absence of controlled studies, judicious use
      of immunosuppressant medications based on the patient's suitability for repeat
      transplantation, anticipated time to repeat transplantation, risk of
      sensitization, and drug tolerance, together with a cohesive plan for CKD
      management and appropriate preparation for dialysis, may improve outcomes in this
      unique patient population.

PMID- 21946164
TI  - Long-term outcomes of kidney donors.
AB  - PURPOSE OF REVIEW: Living kidney donors face a unique decision of self-sacrifice
      that is not without potential risk. The purpose of this review is to highlight
      existing research regarding the perioperative morbidity, mortality and long-term
      outcomes of living kidney donors. RECENT FINDINGS: Recent studies of long-term
      donor survival have affirmed that the life expectancy for living kidney donors is
      excellent and their risk of end-stage renal disease (ESRD) is not increased. Long
      term health outcomes for living donors representing minority groups, however, may
      not be as favorable. Recent studies conclude that African-American and Hispanic
      donors, similarly to nondonors of the same race, are at higher risk of developing
      chronic kidney disease (CKD), hypertension, and diabetes mellitus. Outcomes in
      medically complex donors have also generated considerable attention, and the
      evidence on outcomes among otherwise healthy obese and older donors appears to be
      reassuring. SUMMARY: Living kidney donation is a superior transplantation option
      for many individuals with ESRD. The survival and health consequences of living
      donation have proven to be excellent. These favorable outcomes stem from careful
      screening measures, and further research endeavors are needed to ensure long-term
      living donor safety in high-risk donors.

PMID- 21946165
TI  - Effects of the anti-malarial compound cryptolepine and its analogues in human
      lymphocytes and sperm in the Comet assay.
AB  - Malaria is a mosquito-borne infectious disease caused by the genus Plasmodium. It
      causes one million deaths per year in African children under the age of 5 years.
      There is an increasing development of resistance of malarial parasites to
      chloroquine and other currently used anti-malarial drugs. Some plant products
      such as the indoloquinoline alkaloid cryptolepine have been shown to have potent
      activity against P. falciparum in vitro. On account of its toxicity, cryptolepine
      is not suitable for use as an antimalarial drug but a number of analogues of
      cryptolepine have been synthesised in an attempt to find compounds that have
      reduced cytotoxicity and these have been investigated in the present study in
      human sperm and lymphocytes using the Comet assay. The results suggest that
      cryptolepine and the analogues cause DNA damage in lymphocytes, but appear to
      have no effect on human sperm at the assessed doses. In the context of
      antimalarial drug development, the data suggest that all cryptolepine compounds
      and in particular 2,7-dibromocryptolepine cause DNA damage and therefore may not
      be suitable for pre clinical development as antimalarial agents.

PMID- 21946166
TI  - Time-series analysis of gene expression profiles induced by nitrosamides and
      nitrosamines elucidates modes of action underlying their genotoxicity in human
      colon cells.
AB  - N-nitroso compounds (NOCs) may represent a carcinogenic risk to humans following
      endogenous colonic nitrosation processes. We used the colon adenocarcinoma cell
      line Caco-2 to investigate transcriptomic changes at three time points (1, 6, 24
      h) following exposure to genotoxic concentrations of six different NOCs (two
      nitrosamides, four nitrosamines) with the purpose of identifying biological
      processes that may play a part in the carcinogenicity of these compounds. This is
      especially important for nitrosamide exposure where, in light of their high
      reactivity, important gene expression modifications may take place early in the
      exposure. We also analyzed NOC-induced O(6)-methylguanine adducts in relation to
      transcriptomics since these adducts may influence the expression of genes pivotal
      in NOC-associated carcinogenicity. Many modified pathways appeared related to DNA
      damage, cell cycle, apoptosis, growth factor signaling and differentiation, which
      are linked with carcinogenicity. Nitrosamides showed the strongest response at 1h
      of exposure, while nitrosamines had the strongest effect at 6 and 24 h.
      Additionally, methylation was strongly associated with processes that may
      contribute to the carcinogenic risk. In summary, we have found that NOC-induced
      gene expression changes vary over time and that many of the modified pathways and
      processes indicate a carcinogenic risk associated with NOC exposure.

PMID- 21946167
TI  - Uptake, excretion and toxicity of nano-sized latex particles on medaka (Oryzias
      latipes) embryos and larvae.
AB  - Nanoparticles are particles with diameters of 100 nm or less. As the applications
      of these particles have increased in recent years, their potential impact on the
      physiology of humans and animals has also increased. However, little is known
      regarding the effect of nanoparticles on the physiology of aquatic organisms. In
      this study, we investigated the effect of nano-sized, fluorescent, latex
      particles on the freshwater fish, medaka (Oryzias latipes). Medakas were exposed
      to four different types of fluorescent latex particles and the uptake, excretion,
      and the effect of nanoparticle accumulation on survival rate in medaka larvae
      were examined. These are fluorescent latex particles, which are non
      functionalized 50 and 500 nm in diameter and carboxyl-group functionalized 50 and
      500 nm in diameter. Fluorescence intensity in fish embryos exposed to non
      functionalized and carboxyl-group functionalized particles measuring 50 nm in
      diameter (Particle 50 nm and Particle c50 nm) was markedly higher compared to
      when embryos were exposed to particles measuring 500 nm in diameter (Particle 500
      nm and Particle c500 nm). Moreover, the excretion of nano-sized particles
      (Particle 50 and Particle c50 nm) from embryos was considerably slow, compared to
      larger particles (Particle 500 and Particle c500 nm). In addition, the survival
      rate of larvae exposed to nano-sized particles in small cups was significantly
      lower than the survival rates of fish maintained in larger containers. The
      findings suggested that although the nano-sized fluorescent latex particles were
      not intrinsically toxic, a synergistic toxic effect arose in combination with
      other factors, which is not favorable for fish larvae.

PMID- 21946168
TI  - Size-dependent effects of low level cadmium and zinc exposure on the metabolome
      of the Asian clam, Corbicula fluminea.
AB  - The toxic effects of low level metal contamination in sediments are currently
      poorly understood. We exposed different sized Asian clams, Corbicula fluminea, to
      sediment spiked with environmentally relevant concentrations of either zinc,
      cadmium or a zinc-cadmium mixture for one week. This freshwater bivalve is well
      suited for sediment toxicity tests as it lives partly buried in the sediment and
      utilises sediment particles as a food resource. After one week, the whole tissue
      composition of low molecular weight metabolites was analysed by nuclear magnetic
      resonance spectroscopy (NMR) and gas chromatography-mass spectrometry (GC-MS).
      The condition index (ratio of tissue dry weight to volume inside the shell
      valves) was also measured. Small and large clams were clearly differentiated by
      their metabolic composition and the two size classes showed opposite responses to
      the mixture spiked sediment. No effects of zinc alone on the metabolome were
      found and cadmium only influenced the smaller size class. The main perturbations
      were seen in amino acid and energy metabolism, with small clams using amino acids
      as an energy resource and larger clams primarily drawing on their larger storage
      reserves of carbohydrates. Our study demonstrates that metabolomics is a useful
      technique to test for low level toxicity which does not manifest in mortality or
      condition index changes. The differing effects between the two size classes
      stress that it is important to consider age/size when conducting metabolomic and
      ecotoxicology assessments, since testing for the effects on only one size class
      makes it more difficult to extrapolate laboratory results to the natural
      environment.

PMID- 21946169
TI  - Digestive toxicity in grass shrimp collected along an impact gradient.
AB  - Ingested pollutants may elicit digestive toxicity following incorporation into
      consumer tissues. This post-assimilatory toxicity may include tissue damage
      influencing synthesis of digestive enzymes, gut transit time and absorption of
      nutrients as well as pollutants by the gut epithelium. This study investigated
      impacts of chronic field exposure on gut residence time (GRT), feces elimination
      rate (FER), extracellular digestive protease activities and gut pH in grass
      shrimp Palaemonetes pugio. Adult shrimp were collected from differentially
      impacted sites within the New York/New Jersey Harbor Estuary and fed prepared
      meals containing fluorescent or near-infrared markers and analyzed for digestive
      toxicity. Relationships between digestive parameters and assimilation
      efficiencies (AE) for Cd, Hg and organic carbon reported previously were also
      analyzed. Minimum GRT did not vary significantly for field-collected shrimp, but
      was positively correlated with Cd, but not Hg or carbon, AE. FER was not impacted
      by field exposure. Digestive protease activities exhibited a marked decrease in
      grass shrimp from impacted field sites relative to reference shrimp.
      Relationships between the assimilation of elements and digestive physiology in
      field-collected shrimp suggest that digestive plasticity (increasing GRT) may be
      important in compensating for post-assimilatory digestive toxicity (reduced
      protease activities) in order to maintain nutrient assimilation. Stress-induced
      variability in digestive function among grass shrimp populations may, in turn,
      enhance the assimilation of non-essential elements, such as Cd.

PMID- 21946170
TI  - "Please implant a defibrillator in my patient": it's deja vu all over again.

PMID- 21946171
TI  - Human herpes virus 8 in solid organ transplantation.
AB  - Human herpes virus 8 (HHV-8) is a geographically limited virus that causes
      neoplastic and nonneoplastic diseases predominantly in endemic regions. Primary
      HHV-8 infection, which is usually asymptomatic in immunocompetent individuals,
      result in lifelong latency. When the equilibrium between virus and host immunity
      is disturbed, such as after organ transplantation, HHV-8 may activate molecular
      pathways that drive oncogenesis. Kaposi's sarcoma, primary effusion lymphoma, and
      Castleman's disease are the major malignancies associated with HHV-8. The
      incidences of these neoplastic pathologies mirror the geographic HHV-8
      seroprevalence, and certain groups of patients are at higher risk. In this
      context, the risk of HHV-8 and its clinical disease is highest in
      immunocompromised patients, including transplant recipients. Solid organ
      transplant recipients from HHV-8 endemic regions may develop HHV-8 reactivation
      or primary infection and manifest with Kaposi's sarcoma or less commonly primary
      effusion lymphoma and Castleman's disease; these neoplastic diseases are reported
      much less commonly in low-prevalent areas. There is currently no standard method
      of screening for HHV-8 infection in the transplant setting, although HHV-8
      polymerase chain reaction is available to confirm clinical suspicion of
      infection. Management of HHV-8-associated diseases entails primarily a reduction
      in the degree of pharmacologic immunosuppression and, in some cases, chemotherapy
      may be required. The mammalian target of rapamycin inhibitor sirolimus may have
      the potential for management because of its antiproliferative properties. The
      role of antiviral drugs for HHV-8 prevention and treatment is yet to be defined.

PMID- 21946173
TI  - Is it time to extend liver acceptance criteria for controlled donors after
      cardiac death?
AB  - BACKGROUND: Donation after cardiac death (DCD) has reemerged as potential way to
      increase donor liver availability. Earlier, programs with DCD liver
      transplantation used conservative donor criteria to allow safe results.
      Successful initial outcomes allowed extended DCD criteria to address transplant
      demand. METHODS: A total of 63 DCD liver grafts were used during the study period
      in carefully selected recipients. These were divided into two groups: "Standard"
      DCD within conservative criteria (n=33; age <=60 years, body mass index <30
      kg/m(2), donor warm ischemia time <=30 min, and cold ischemia time <=8 hr) and
      "Extended" DCD beyond these criteria (n=30). We compared donor and recipient
      characteristics and postoperative outcomes, including patient and graft survival.
      RESULTS: Both groups had satisfactory initial function; liver graft function at
      1, 7, and 30 days after liver transplantation were similar. Median follow-up
      period was 25 and 18.5 months for Standard and Extended criteria DCD grafts,
      respectively, with 1-year patient and graft survival of 88% and 82% for the
      Standard group vs. 90% and 90% for the Extended. Overall, 8 of 63 (13%) patients
      developed biliary complications; however, the incidence was not different between
      the Standard and Extended groups. Seven early deaths occurred, four and three in
      the Standard and Extended groups, respectively. CONCLUSIONS: Recipients of DCDs
      beyond conventional acceptance criteria have equivalent early outcomes to
      standard DCD grafts. With careful selection of donors and recipients, these
      grafts can be safely used to expand the donor pool.

PMID- 21946172
TI  - Detection of polyomavirus BK reactivation after renal transplantation using an
      intensive decoy cell surveillance program is cost-effective.
AB  - BACKGROUND: Reactivation of polyomavirus BK (BKV) after renal transplantation can
      lead to allograft dysfunction or loss with early detection improving outcomes.
      Current guidelines recommend quantitative polymerase chain reaction for
      surveillance; however, urinary decoy cell detection is a potentially cost
      effective alternative. We present the outcomes from an early intensive BKV
      surveillance program using decoy cell detection for initial screening starting 2
      weeks after transplantation. METHODS: Records for all recipients of kidney
      (n=211) or simultaneous kidney and pancreas (n=102) transplants performed over 2
      years in a single center were reviewed. Follow-up was for a minimum of 1 year.
      Urine cytology screening was performed fortnightly from 0 to 3 months after
      transplantation, monthly from 3 to 6 months then every 2 months from 6 to 12
      months. RESULTS: Decoy cell positivity occurred in 56 of 313 patients (17.9%)
      with sustained decoy cell positivity (>=2 positive urine samples >2 weeks apart)
      present in 32 patients (10.2%). Twenty-four patients (7.6%) became viremic and
      three patients (1%) developed polyoma virus nephropathy. The median time after
      transplantation until decoy cell positivity was 78 days, decreasing to 67 days
      for patients with sustained positivity and 57 days for patients who developed
      polyoma virus nephropathy. No grafts were lost due to BKV during the study
      period. Decoy cell screening resulted in savings of approximately L135,000 over 2
      years, when compared with routine surveillance by quantitative polymerase chain
      reaction. CONCLUSIONS: Clinically significant BKV reactivation occurs early after
      transplantation and can be reliably detected by decoy cell screening. A
      surveillance strategy for detecting BKV reactivation based on urine cytology is
      cost-effective.

PMID- 21946174
TI  - Kinetics of anti-blood type isoagglutinin titers and B lymphocytes in ABO
      incompatible living donor liver transplantation with rituximab and plasma
      exchange.
AB  - BACKGROUND: A novel immunosuppression protocol using rituximab and plasma
      exchange treatment was developed for ABO-incompatible living donor liver
      transplantation (ABO-I LDLT). The aim of this study was to investigate the
      kinetics of anti-blood type isoagglutinin titers and the number of blood B
      lymphocytes in ABO-I LDLT with the new protocol and their impact on the outcomes
      after ABO-I LDLT. METHODS: Fifteen patients underwent ABO-I LDLT plus splenectomy
      with the new protocol between November 2005 and December 2010, and their data
      were retrospectively analyzed. RESULTS: CD19-positive lymphocytes in the blood
      rapidly disappeared after rituximab treatment and began to recover approximately
      6 months later. Anti-blood type isoagglutinin titers were lowered by
      pretransplant plasma exchange (2(3)~2(12)->2(1)~2(8)). Although the anti-donor
      blood type isoagglutinin titers remained consistently low after transplantation
      in comparison to the pretreatment levels, they persisted long after LDLT, whereas
      posttransplant biopsy specimens showed sustained A/B antigens on the graft
      livers. ABO-I hepatitis C virus-positive patients were prone to acceleration of
      hepatitis C viremia and cytomegalovirus antigenemia in comparison to the control
      patients. CONCLUSIONS: Although the new protocol for ABO-I LDLT yielded great
      success with 100% graft survival, the acceptable anti-blood type isoagglutinin
      titers just before LDLT, and its application to hepatitis C-positive patients
      must be determined.

PMID- 21946175
TI  - Genome wide association studies (GWAS) and copy number variation (CNV) studies of
      the major psychoses: what have we learnt?
AB  - Schizophrenia (SZ) and bipolar disorder (BPD) have high heritabilities and are
      clinically and genetically complex. Genome wide association studies (GWAS) and
      studies of copy number variations (CNV) in SZ and BPD have allowed probing of
      their underlying genetic risks. In this systematic review, we assess extant
      genetic signals from published GWAS and CNV studies of SZ and BPD up till March
      2011. Risk genes associated with SZ at genome wide significance level (p
      value<7.2 * 10(-8)) include zinc finger binding protein 804A (ZNF804A), major
      histocompatibility (MHC) region on chromosome 6, neurogranin (NRGN) and
      transcription factor 4 (TCF4). Risk genes associated with BPD include ankyrin 3,
      node of Ranvier (ANK3), calcium channel, voltage dependent, L type, alpha 1C
      subunit (CACNA1C), diacylglycerol kinase eta (DGKH), gene locus on chromosome
      16p12, and polybromo-1 (PBRM1) and very recently neurocan gene (NCAN). Possible
      common genes underlying psychosis include ZNF804A, CACNA1C, NRGN and PBRM1. The
      CNV studies suggest that whilst CNVs are found in both SZ and BPD, the large
      deletions and duplications are more likely found in SZ rather than BPD. The
      validation of any genetic signal is likely confounded by genetic and phenotypic
      heterogeneities which are influenced by epistatic, epigenetic and gene
      environment interactions. There is a pressing need to better integrate the
      multiple research platforms including systems biology computational models,
      genomics, cross disorder phenotyping studies, transcriptomics, proteomics,
      metabolomics, neuroimaging and clinical correlations in order to get us closer to
      a more enlightened understanding of the genetic and biological basis underlying
      these potentially crippling conditions.

PMID- 21946176
TI  - Immediate surge in female visits to the cardiac emergency department following
      the economic collapse in Iceland: an observational study.
AB  - OBJECTIVE: To study potential changes in attendance at emergency departments (ED)
      in Reykjavik immediately following the swift economic meltdown in Iceland in
      October 2008. METHODS: Using electronic medical records of the National
      University Hospital in Reykjavik, a population-based register study was conducted
      contrasting weekly attendance rates at Reykjavik ED (cardiac and general ED)
      during 10-week periods in 2006, 2007 and 2008. The weekly number of all ED visits
      (major track), with discharge diagnoses, per total population at risk were used
      to estimate RR and 95% CI of ED attendance in weeks 41-46 (after the 2008
      economic collapse) with the weekly average number of visits during weeks 37-40
      (before the collapse) as reference. RESULTS: Compared with the preceding weeks
      (37-40), the economic collapse in week 41 2008 was associated with a distinct
      increase in the total number of visits to the cardiac ED (RR 1.26; 95% CI 1.07 to
      1.49), particularly among women (RR 1.41; 95% CI 1.17 to 1.69) and marginally
      among men (RR 1.15; 95% CI 0.96 to 1.37). A similar increase was not observed in
      week 41 at the general ED in 2008 or in either ED in 2007 or 2006. In week 41
      2008, visits with ischaemic heart disease as discharge diagnoses (ICD-10: I20-25)
      were increased among women (RR 1.79; 95% CI 1.01 to 3.17) but not among men (RR
      1.07; 95% CI 0.71 to 1.62). CONCLUSION: The dramatic economic collapse in Iceland
      in October 2008 was associated with an immediate short-term increase in female
      attendance at the cardiac ED.

PMID- 21946177
TI  - Paediatric arrhythmias in the emergency department.
AB  - OBJECTIVE: Emergency department (ED) staff need to rapidly establish accurate
      diagnosis and management for children with arrhythmias. Limited data are
      available on the presenting features, epidemiology and management of arrhythmias
      encountered in the ED. The aim of this study was to characterise the incidence,
      presenting features, management and outcomes of arrhythmias at a large tertiary
      children's hospital ED. PATIENTS AND METHODS: Retrospective review of medical
      records identified via the ED electronic database using ICD-10 codes for
      arrhythmias including cardiac arrests over a 6-year period (2002-2008). Patients
      <18 years were analysed using predefined criteria. RESULTS: There were a total of
      444 non-arrest arrhythmias with an incidence of 11.5:10 000 presentations. Median
      age of patients at presentation was 10.4 years; 45% were male. Supraventricular
      arrhythmias (SVTs) represented the largest subgroup (n=250, 56%). Conduction
      disorders (n=18), ventricular tachycardia (n=17) and atrial flutter/fibrillation
      (n=7) were rare. There were 19 cardiac arrests. Fifty-seven (13%) patients had
      underlying congenital heart disease. For ongoing SVT (n=135), vagal manoeuvres
      were used in 74%, and antiarrhythmic drugs in 64%. In five patients with SVT,
      drugs other than adenosine were used. Defibrillators were used only on 2
      occasions for arrthymias and 6 times for cardiac arrests. 18 of 19 children in
      cardiac arrest died. CONCLUSION: In this largest paediatric series outside the
      intensive care and postoperative setting, arrhythmias were uncommon,
      defibrillator use was very rare, and observed mortality was low.

PMID- 21946178
TI  - Use of healthcare information and advice among non-urgent patients visiting
      emergency department or primary care.
AB  - BACKGROUND: Healthcare information provided by telephone service and internet
      sources is growing but has not been shown to reduce inappropriate emergency
      department (ED) visits. OBJECTIVE: To describe the use of advice or healthcare
      information among patients with non-urgent illnesses seeking care before
      attendance at an ED, or primary care (PC) centres in an urban region in Sweden.
      DESIGN: Patients with non-urgent illnesses seeking care at an ED or patients
      attending the PC were followed up with a combination of patient interviews, a
      questionnaire to the treating physician and a prospective follow-up of healthcare
      use through a population-based registry. RESULTS: Half of the non-urgent patients
      attending the ED had used healthcare information or advice before the visit,
      mainly from a healthcare professional source. In PC, men were more likely to have
      used information or advice compared with women (OR 2.5 95% CI 1.3 to 5.0),
      whereas the situation was reversed among ED patients (OR=0.4 95% CI 0.2 to 0.9).
      Men with no previous healthcare experience attending the ED had the lowest use of
      healthcare information (p<0.01). Very few in both groups had utilised healthcare
      information on the internet in a case of perceived emergency. CONCLUSION: ED
      patients rated as non-urgent by the triage nurse used more advice and healthcare
      information than PC patients, irrespective of the physician-rated urgency of the
      symptoms. The problem seems not to be lack of information about appropriate ED
      use, but to find ways to direct the information to the right target group.

PMID- 21946179
TI  - The prognostic value of tissue oxygen saturation in emergency department patients
      with severe sepsis or septic shock.
AB  - OBJECTIVES: To determine the derangement of muscle tissue oxygen saturation
      (StO(2)) in the early phase of emergency department (ED) sepsis management and
      its relationship to 30-day mortality in patients with severe sepsis or septic
      shock. METHODS: A prospective cohort study conducted in the ED of a university
      hospital. Patients were included if they had a clinical diagnosis of severe
      sepsis or septic shock. Thenar muscle tissue StO(2) on arrival in the ED and its
      change with usual ED sepsis management was measured using near-infrared
      spectroscopy. A follow-up measurement was obtained after 24 h of treatment. All
      patients were followed for 30 days. RESULTS: 49 patients were included, of which
      24 (49%) died. There was no difference in mean StO(2) on arrival in the ED
      between survivors and non-survivors (72% vs 72%; p=0.97). Following ED treatment
      the mean StO(2) of survivors improved significantly to 78% (p<0.05) while StO(2)
      remained persistently low in non-survivors (p=0.94). Persistently low StO(2)
      (<75%) despite initial resuscitative treatment was associated with a twofold
      increase in mortality (RR of death 2.1%; 95% CI 1.2% to 3.5%). CONCLUSION:
      Patients with severe sepsis/septic shock have abnormal muscle tissue StO(2) upon
      arrival in the ED. Inability to normalise StO(2) with ED sepsis management is
      associated with a poor outcome. The role of StO(2) as an early prognostic and
      potential therapeutic biomarker in severe sepsis or septic shock warrants further
      exploration.

PMID- 21946180
TI  - An analysis of outcomes of emergency physician/department-based thrombolysis for
      stroke.
AB  - BACKGROUND: Stroke thrombolysis is strongly supported as an effective therapy for
      selected cases of early stroke. The absence of 24 h stroke specialists in
      district general hospitals (DGHs) has led to the suggestion that regional hyper
      acute stroke centres should be developed. This paper describes a cooperative
      model that uses the skills already present in a DGH to deliver a thrombolysis
      service initiated in the emergency department by the emergency physicians, and
      describes the outcomes of that service in comparison with the SITS-MOST trial.
      METHOD: The outcomes of all stroke patients thrombolysed at Scarborough DGH from
      2004 to January 2009 were reviewed. Outcome was defined using a three-part scale.
      Data at Scarborough DGH were compared with data from the SITS-MOST European-wide
      study of stroke thrombolysis. RESULTS: Data were available for 98 of 110 patients
      thrombolysed during the study period. Fifty (51%) had a good outcome, seven (8%)
      had partial resolution of their symptoms, and 41 (42%) showed no improvement or
      deterioration. These outcomes were comparable to those in the European database.
      CONCLUSION: Stroke thrombolysis can be effectively delivered in a non-specialist
      (a non-hyper-acute stroke centre) DGH in the UK. An audit of cases completed
      describes complications seen.

PMID- 21946181
TI  - Upper extremity deep venous thrombosis....can you spot the culprit?

PMID- 21946182
TI  - Homemade ultrasound phantom for teaching identification of superficial soft
      tissue abscess.
AB  - BACKGROUND: Point-of-care ultrasonography (POCUS) is often used to distinguish
      abscess from cellulitis in superficial soft tissue infections. With the increased
      use of POCUS in emergency medicine, it is important that training to use POCUS is
      enhanced by practice using phantom models. OBJECTIVE: To create an easily made,
      inexpensive, homemade phantom capable of simulating an abscess in superficial
      soft tissue infection. METHODS: Increasing amounts of Jell-O (Northfield,
      Illinois, USA) brand gelatin and sugar-free Metamucil (Cincinnati, Ohio, USA)
      brand psyllium hydrophilic mucilloid fibre were experimented with until a
      satisfactory model was achieved. Various liquids were injected into it to
      simulate superficial abscess formation. The desired goal was for the phantom to
      appear similar to superficial human soft tissue under ultrasound scan and to be
      firm enough to withstand pressure from an ultrasound probe scan. The goal for the
      simulated abscess was to appear as a hypoechoic space under ultrasound scan. A
      Sonosite M-Turbo (Bothell, Washington, USA) bedside ultrasound machine with
      linear array transducer probe was used for the ultrasound scans. RESULTS: The
      optimal homemade phantom incorporated 12 tablespoons of Jell-O and four
      tablespoons of Metamucil in one liter of water. CONCLUSION: An easily made,
      inexpensive phantom model for instruction on identification of superficial skin
      abscess was achieved.

PMID- 21946183
TI  - A pilot study of motivational interviewing training in a virtual world.
AB  - BACKGROUND: Motivational interviewing (MI) is an evidence-based, patient-centered
      counseling strategy proven to support patients seeking health behavior change.
      Yet the time and travel commitment for MI training is often a barrier to the
      adoption of MI by health care professionals. Virtual worlds such as Second Life
      (SL) are rapidly becoming part of the educational technology landscape and offer
      not only the potential to improve access to MI training but also to deepen the MI
      training experience through the use of immersive online environments. Despite
      SL's potential for medical education applications, little work is published
      studying its use for this purpose and still less is known of educational outcomes
      for physician training in MI using a virtual-world platform. OBJECTIVE: Our aims
      were to (1) explore the feasibility, acceptability, and effectiveness of a
      virtual-world platform for delivering MI training designed for physicians and (2)
      pilot test instructional designs using SL for MI training. METHODS: We designed
      and pilot tested an MI training program in the SL virtual world. We trained and
      enrolled 13 primary care physicians in a two-session, interactive program in SL
      on the use of MI for counseling patients about colorectal cancer screening. We
      measured self-reported changes in confidence and clinical practice patterns for
      counseling on colorectal cancer screening, and acceptability of the virtual-world
      learning environment and the MI instructional design. Effectiveness of the MI
      training was assessed by coding and scoring tape-recorded interviews with a
      blinded mock patient conducted pre- and post-training. RESULTS: A total of 13
      physicians completed the training. Acceptability ratings for the MI training
      ranged from 4.1 to 4.7 on a 5-point scale. The SL learning environment was also
      highly rated, with 77% (n = 10) of the doctors reporting SL to be an effective
      educational medium. Learners' confidence and clinical practice patterns for
      colorectal cancer screening improved after training. Pre- to post-training mean
      confidence scores for the ability to elicit and address barriers to colorectal
      cancer screening (4.5 to 6.2, P = .004) and knowledge of decision-making
      psychology (4.5 to 5.7, P = .02) and behavior change psychology (4.9 to 6.2, P =
      .02) increased significantly. Global MI skills scores increased significantly and
      component scores for the MI skills also increased, with statistically significant
      improvements in 4 of the 5 component skills: empathy (3.12 to 3.85, P = .001),
      autonomy (3.07 to 3.85, P < .001), collaboration (2.88 to 3.46, P = .02), and
      evocative response (2.80 to 3.61, P = .008). CONCLUSIONS: The results of this
      pilot study suggest that virtual worlds offer the potential for a new medical
      education pedagogy that will enhance learning outcomes for patient-centered
      communication skills training.

PMID- 21946184
TI  - Modulation of microRNAs during exercise and disease in human skeletal muscle.

PMID- 21946188
TI  - Infant pertussis: is cocooning the answer?

PMID- 21946189
TI  - An optimal body mass index range associated with improved immune reconstitution
      among HIV-infected adults initiating antiretroviral therapy.
AB  - BACKGROUND: Higher body mass index (BMI) was associated with slower human
      immunodeficiency virus (HIV) disease progression before the availability of
      effective antiretroviral therapy (ART), but the relationship between pretreatment
      BMI and CD4(+) lymphocyte recovery on ART is not well described. METHODS: We
      conducted an observational cohort study of HIV-infected, ART-naive adults
      starting treatment at a clinic affiliated with Vanderbilt University in
      Nashville, Tennessee. We assessed the relationship between pretreatment BMI and
      CD4(+) lymphocyte count change from baseline to 12 months in all subjects, among
      those with plasma HIV-1 RNA levels <400 copies/mL for >= 6 months and those with
      <10% change in weight during follow-up. Linear regression models were adjusted
      for age, sex, race, protease inhibitor usage, year of ART initiation, and
      baseline CD4(+) lymphocyte count and HIV-1 RNA level. RESULTS: A total of 915
      patients met inclusion criteria; 78% were male, and their median age, BMI, and
      CD4(+) lymphocyte count were 39 years, 24 kg/m2, and 171 cells/MUL, respectively.
      The CD4(+) lymphocyte increase at 12 months was greatest among patients with a
      pretreatment BMI of ~25-30 kg/m2 and diminished above and below this range (P =
      .03). Similar patterns were observed in the subgroup analyses. Among patients
      with a pretreatment CD4(+) lymphocyte count < 200 cells/MUL, a BMI of ~25 kg/m2
      was associated with the highest odds of reaching a CD4(+) lymphocyte count > 350
      cells/MUL at 12 months (P = .05). CONCLUSIONS: 12-month immune reconstitution on
      ART was highest among patients commonly classified as overweight, suggesting
      there may be an optimal BMI range for immune recovery on ART.

PMID- 21946190
TI  - Kinetics of the antibody response to tetanus-diphtheria-acellular pertussis
      vaccine in women of childbearing age and postpartum women.
AB  - BACKGROUND: Because adolescents and adults act as a primary source of pertussis
      infection for infants, vaccination of mothers immediately postpartum is a
      potential strategy to reduce transmission (cocoon strategy). For this to be
      effective, high levels of antibodies must be achieved rapidly after vaccination.
      We sought to determine whether the antibody response to tetanus-diphtheria
      acellular pertussis vaccine (Tdap) is sufficiently rapid to support the cocoon
      strategy. METHODS: Two sequential studies were performed. The first was a
      nonrandomized, open study of a 5-pertussis-component Tdap vaccine (tetanus
      toxoid, diphtheria toxoid, pertussis toxoid [PT], filamentous hemagglutinin
      [FHA], fimbriae types 2 and 3 [FIM], and pertactin [PRN]) given to women of
      childbearing age; the second was a randomized, open study of Tdap or no vaccine
      in postpartum women. Serum levels of immunoglobin (Ig) G and IgA against
      pertussis antigens, serum levels of IgG against diphtheria and tetanus, and
      breast milk levels of IgA against pertussis antigens were measured at various
      times after vaccination. RESULTS: In both studies, the antibody response was
      relatively rapid, with serum IgG and IgA levels beginning to increase noticeably
      by days 5-7 and approaching peak levels by day 14. Greater than 68% and 84.4% of
      IgG and IgA responders, respectively, achieved >= 90% of their maximum titer by
      day 14. The diphtheria and tetanus antibody kinetics followed a similar time
      course. Breast milk levels of IgA against PT, FHA, and FIM were first detectable
      at day 7, peaked by day 10, and then slowly decreased through day 28. Antibodies
      against PRN showed a similar response, although the peak occurred at day 14.
      There were no significant antibody responses in the control group. CONCLUSIONS:
      Although the antibody response to a dose of Tdap in healthy nonpregnant women of
      child-bearing age and postpartum women occurs by day 14 and is suggestive of an
      anamnestic immune response, it may not be sufficiently rapid to protect infants
      in the first weeks of life.

PMID- 21946191
TI  - Comparative long-term adverse effects elicited by invasive group B and C
      meningococcal infections.
AB  - BACKGROUND: Given the identity between Neisseria meningitidis serogroup B (MenB)
      capsular polysaccharide (polysialic acid; PSA) and PSA found on neural cell
      adhesion molecules, it has been proposed that infection with MenB or vaccination
      with PSA may be associated with subsequent autoimmune or neurological disease.
      METHODS: We conducted 2 studies. The first was a retrospective nationwide study
      of invasive meningococcal disease (IMD) in Iceland (with 541 subjects) during the
      period 1975-2004, and we cross referenced this cohort with databases with respect
      to subsequent diagnosis of autoimmune disorders. A follow-up study involving 120
      survivors of IMD was performed. The study included 70 patients with a history of
      MenB and 50 patients with N. meningitidis serogroup C (MenC) infection, who
      served as control subjects. Participants answered standardized questionnaires
      (Beck's Depression Inventory [BDI] II, Depression Anxiety Stress Scales [DASS],
      and Patient Health Questionnaire [PHQ]), and serum levels of immunoglobulin (Ig)
      G against MenB and MenC capsular polysaccharides were measured. RESULTS: The
      nationwide cohort had 9166 patient-years of follow up. No evidence of increased
      autoimmunity was found to be associated with MenB, compared with MenC. In the
      follow-up study, patients were evaluated 16.6 years after the infection,
      representing 2022 patient-years of observation. Comparable rates of most
      complications were recorded, but MenC infections were associated with arthritis
      (P = .008) and migraine headaches (P = .01) more frequently than were MenB
      infections. No difference was observed with respect to scores on BDI-II, DASS, or
      PHQ. IgG anti-MenB and anti-MenC capsular polysaccharide levels were not related
      to patient complaints. CONCLUSIONS: This study does not support the hypothesis
      that MenB infection may predispose to autoimmunity. MenC infections are
      associated with a higher prevalence of arthritis and migraine headaches. No
      evidence of antibody-associated pathology was detected at long-term follow-up.

PMID- 21946192
TI  - Differential modulation of brainstem phosphatidylinositol 3-kinase/Akt and
      extracellular signal-regulated kinase 1/2 signaling underlies WIN55,212-2
      centrally mediated pressor response in conscious rats.
AB  - Our recent study demonstrated that central cannabinoid receptor 1 (CB1R)
      activation caused dose-related pressor response in conscious rats, and reported
      studies implicated the brainstem phosphatidylinositol 3-kinase (PI3K)/Akt
      extracellular signal-regulated kinase 1/2 (ERK1/2) pathway in blood pressure
      control. Therefore, in this study, we tested the hypothesis that the modulation
      of brainstem PI3K/Akt-ERK1/2 signaling plays a critical role in the central
      CB(1)R-mediated pressor response. In conscious freely moving rats, the pressor
      response elicited by intracisternal (i.c.) (R)-(+)-[2,3-dihydro-5-methyl-3[(4
      morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl) methanone
      mesylate salt (WIN55,212-2) (15 MUg) was associated with significant increases in
      ERK1/2 phosphorylation in the rostral ventrolateral medulla (RVLM) and the
      nucleus tractus solitarius (NTS). In contrast, Akt phosphorylation was
      significantly reduced in the same neuronal pools. Pretreatment with the selective
      CB1R antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4
      methyl-1H-pyrazole-3-carboxamide (AM251) (30 MUg i.c.) attenuated the
      neurochemical responses elicited by central CB1R activation. Furthermore,
      pretreatment with the ERK/mitogen-activated protein kinase kinase inhibitor 2'
      amino-3'-methoxyflavone (PD98059) (5 MUg i.c.) abrogated WIN55,212-2-evoked
      increases in blood pressure and neuronal ERK1/2 phosphorylation but not the
      reduction in Akt phosphorylation. On the other hand, prior PI3K inhibition with
      wortmannin (0.4 MUg i.c.) exacerbated the WIN55,212-2 (7.5 and 15 MUg i.c.) dose
      related increases in blood pressure and ERK1/2 phosphorylation in the RVLM. The
      present neurochemical and integrative studies yield new insight into the critical
      role of two brainstem kinases, PI3K and ERK1/2, in the pressor response elicited
      by central CB1R activation in conscious rats.

PMID- 21946193
TI  - Sickness behavior clustering in children with cancer.
AB  - Despite knowing that pediatric cancer patients experience multiple concurrent
      symptoms, most research focuses on individual symptoms. This study is a secondary
      data analysis from previous research evaluating symptom clusters and carnitine
      plasma levels in 67 children and adolescents aged between 7 and 18 years, before
      and after receiving ifosfamide, doxorubicin, or cisplatin chemotherapy. In
      preparation for cluster analysis, fatigue, nausea and vomiting, depression, and
      performance status symptoms were rated in categories of none, mild, moderate, or
      severe. A conceptual approach was used to evaluate the identification of unique
      patterns of symptoms that cluster as well as what subgroup members of pediatric
      oncology patients assemble together. Comparison of symptoms is made with the
      recent literature on sickness behavior symptoms. The hierarchical agglomerative
      cluster analysis was used to identify and classify variables into groups based on
      similarities they possess. This cluster analysis increases awareness of sickness
      behavior symptoms, patterns, interaction, and synergy. Increasing knowledge of
      the complex symptom experiences of pediatric oncology patients provides the
      scientific basis for new directions in symptom intervention.

PMID- 21946194
TI  - Comparing administration of nutrition support with prescribed dose.
AB  - The aim of this study was to evaluate whether pediatric bone marrow transplant
      (BMT) patients receive the prescribed dose of nutrition support (NS). Data were
      obtained from electronic and paper charts at St. Jude Children's Research
      Hospital. The amount of NS received was compared with the amount prescribed. Data
      were collected on 32 patients for 63 hospital stays in which NS was administered.
      The mean percentage of nutrition prescription met and percentage of total
      estimated energy met were 69% and 72%, respectively. Allogeneic BMT patients
      received significantly more of their nutrition prescription (92%) than autologous
      BMT patients did (54%, P < .01). Malnourished patients were significantly more
      likely to receive the full dose of NS than patients who were considered nourished
      or obese (P < .05). This study showed that patients who were most in need of NS
      were more likely to receive the full dose.

PMID- 21946195
TI  - Education given to parents of children newly diagnosed with acute lymphoblastic
      leukemia: a narrative review.
AB  - Over the past 30 years, diagnosis and treatment of childhood cancers has
      developed significantly due to medical research and advancements in technology.
      As a result, prognosis has improved, and approximately 80% of children diagnosed
      with cancer survive into adulthood. Care has also shifted from a sole inpatient
      setting to include outpatient treatment where possible, and both these trends
      have resulted in a shift in the focus of research to the psychosocial and
      psychological effects of treatment on children and their families. Increasingly,
      parents are taking on the role of providing "nursing" care for their children,
      for example, managing medications and emergency situations as well as everyday
      treatment needs. This article critically reviews the current literature
      surrounding the approaches and methods used by nursing staff to educate families
      to perform this care within the context of a planned first discharge from
      hospital. Twenty-two relevant articles were identified covering different aspects
      of education and discharge planning, including the following: facilitation of
      education and discharge planning, collaboration between professional disciplines
      and family, responsibilities and contractual agreements, timing and approach,
      care planning, and the information needs of families. Only 4 articles discussed
      what the family felt they needed to know and be prepared for prior to discharge.
      This review indicates that further research is required to establish the needs of
      parents and caregivers with regard to education prior to their child's first
      discharge from hospital in the pediatric hematology and oncology setting.

PMID- 21946196
TI  - [High fat diet induces obesity and alters the expression  of MCHR1 and OB-Rb in
      the adipose tissue].
AB  - OBJECTIVE: To investigate the effect of high-fat (HF) diet on the body weight and
      the mRNA expression of melanin concentrating hormone receptor 1 (MCHR1) and
      leptin receptor (OB-Rb) in the adipose tissue in rats, the two important and
      opposite factors in regulating the body weight. METHODS: Post-weaning rats were
      divided into 3 groups: the NC group were fed a normal-chow diet (NC) (13%
      calories from fat), the HF group with a HF-diet (47% calories from fat) and the
      PHF group pair-fed a HF-diet (47% calories from fat). At the end of 8th week, the
      gained bodyweight, the plasma melanin concentrating hormone (MCH) and leptin, and
      the expression levels of MCHR1 and OB-Rb in the adipose tissue were measured.
      RESULTS: Both the HF-diet and pair-fed HF-diet enhanced the body weight (P<0.01),
      plasma MCH (P<0.01) and leptin concentrations (P<0.05). In the adipose tissue, HF
      diet resulted in significant increase in MCHR1 (PHF group,P<0.05) and decrease in
      OB-Rb mRNA levels (HF group,P<0.01; PHF group,P<0.05). No statistical difference
      was found between the HF group and the PHF group in terms of the aforementioned
      data (P>0.05). CONCLUSION: Chronic intake of iso-caloric HF-diet and ad libitum
      HF-diet obviously results in increase in the body weight, serum leptin, and MCH
      concentration. Diet-induced obesity and related metabolic disorders are possibly
      correlated with up-regulated expression of MCHR1 and down-regulated expression of
      OB-Rb in the adipose tissue.

PMID- 21946197
TI  - [Impact of heparin on coagulation index during the  therapy of molecular
      adsorbent recirculating system  in patients with liver failure].
AB  - OBJECTIVE: To investigate the impact of coagulative parameters on different
      anticoagulation systems in molecular adsorbent recirculating system (MARS) in
      subjects with liver failure, and to evaluate the safety of different
      anticoagulation methods . METHODS: A prospective experimental observation was
      designed. According to anticoagulation Methods , 174 MARS treatment sessions for
      146 patients with liver failure and prothrombin time activity percentage (PTA) <=
      40% were randomly divided into 2 groups: 92 MARS treatment sessions in the
      heparin-free group and 82 in the low-dose heparin group. Time points of 0, 0.5,
      1, 2, 3, 4, 5 and 6 h were selected to observe the coagulation changes of
      prothrombin time (PT), PTA, thrombin time (TT), activated partial thromboplastin
      time (APTT) and international normalized ratio (INR) dynamically. Adverse events
      such as line / filter coagulation, rupture and bleeding were also investigated
      and compared due to frequency and severity between the 2 groups. RESULTS: There
      was no difference in PT, PTA, INR between the 2 groups, but significant
      differences were observed in APTT and TT and fibrinogen (Fbg). APTT and TT levels
      in the low-dose heparin group was increased rapidly after the first given dose of
      anticoagulant heparin and reached the peak within 30 min.The levels at each time
      point was statistically different between the 2 groups (P<0.05). A significant
      difference in the Fbg level was obtained between the 2 groups. In the low-dose
      heparin group it was stabilized and increased slightly at the end of the
      treatment. While in the heparin-free group it was decreased gradually and reached
      a ravine at the end of the treatment. A curve was observed after 2.5 h treatment
      between the 2 groups (P=0.001). There were 2 cases of severe bleeding after MARS
      was finished in the heparin group, and 1 was terminated because of degree III
      clotting in the heparin-free group. CONCLUSION: Fibrinogen should be adsorbed
      while the blood touches the MARS circuit path and anticoagulants can prevent it.
      Comprehensive analysis of blood platelet count (BPC), fibrin degradation products
      (FDP), D-dimer and clinical symptoms is critical and required to determine the
      coagulation status to select an anticoagulation system before MARS. The use of
      low dose heparin in MARS improves the disorder of hypercoagulable state during
      the high coaguation period, while heparin-free during low coagulation period can
      effectively prevent the occurrence of bleeding and improve the mechanism of blood
      coagulation by reducing heparin-like substance in the blood.

PMID- 21946198
TI  - [DNA  damage caused by suicide gene therapy system  under Tet-On regulation in
      breast cancer cells].
AB  - OBJECTIVE: To determine the effect and molecular mechanism of DNA damage caused
      by suicide gene therapy system HSV-TK/GCV under Tet-On regulation in human breast
      cancer cell line MCF-7 infected by recombinant adeno-associated virus (rAAV).
      METHODS: We used comet assay to detect the effect of HSV-TK/GCV suicide gene
      regulation system on MCF-7 DNA damage, and analyzed the expression change of
      relative DNA damage response active genes and proteins with RT-PCR and Western
      blot. RESULTS: Compared with other control groups, the comet assay showed that
      MCF-7 cells with HSV-TK/GCV treatment had obvious comet tails, and the expression
      level of DNA damage response active genes and proteins changed obviously in the
      HSV-TK/GCV treatment group,such as ATM, p53 and p27,but CyclinE and CDK2 did not
      change. CONCLUSION: DNA damage on MCF-7 cells is resulted from HSV-TK/GCV in
      suicide gene therapy system through a p53-dependent signal pathway, causing cell
      cycle arrest and cell death.

PMID- 21946199
TI  - [Effect of anti-Helicobacter pylori on the prognosis  in patients with acute
      cerebral infarction].
AB  - OBJECTIVE: To investigate the effect of anti-Helicobacter pylori on the
      inflammation mediators and prognosis in patients with acute cerebral infarction.
      METHODS: Routine urease test was carried out in patients with acute cerebral
      infarction in our hospital. The acute cerebral infarction patients with positive
      urease test were randomly divided into a treatment group (conventional
      therapy+anti-Helicobacter pylori therapy) and a control group (conventional
      therapy). C-reactive protein, triglycerides, and fibrinogen changes were examined
      before and after the treatment, symptoms of acute cerebral infarction conditions
      were observed,and 6-months and 1- year cerebral infarction readmission rates were
      measured in the 2 groups. RESULTS: Compared with before the treatment,the C
      reactive protein, triglycerides, and plasma fibrinogen decreased significantly in
      the treatment group, while there was no significant change in the control group.
      The 6-months and 1-year cerebral infarction readmission rates were significantly
      lower than those in the control group. CONCLUSION: H. pylori infection may be a
      risk factor for cerebral infarction. A positive anti-Helicobacter pylori
      infection treatment can significantly improve the efficiency of cerebral
      infarction and reduce the short-term readmission rate.

PMID- 21946200
TI  - [MicroRNA-29 and fibrosis diseases].
AB  - MicroRNAs (miRNAs,miR) are small, noncoding RNAs with 21-23 nucleotides. MicroRNA
      29 (miR-29), a newly discovered miRNAs, is closely related with fibrosis
      diseases. MiR-29 directly suppresses the expression of a variety of extracellular
      matrix components and regulates signaling pathways associated with fibrosis. The
      serum level of miR-29 in patients with liver disease is consistent with the
      degree of liver cirrhosis.

PMID- 21946201
TI  - [Proteomics of the colonic mucosa in sub-healthy  people with shapeless stool].
AB  - OBJECTIVE: To establish the 2-dimensional electrophoresis (2-DE) map in colonic
      mucosa in sub-healthy people with shapeless stool and healthy people, to identify
      the differential proteins by matrix-assisted laser desorption/ionization time of
      flight mass spectrometry (MALDI-TOF-MS), and to provide theoretical basis for the
      pathogenesis of intestinal mucosa in sub-healthy people with shapeless stool.
      METHODS: Two-DE was used to separate the total proteins from the intestinal
      mucosa in sub-healthy people (the sub-health group) with the shapeless stool and
      healthy volunteers (the control group). ImageMaster 2D Elite soft was applied to
      analyze the 2-DE images, and the differentially expressed protein spots between
      the 2 groups were identified by MALDI-TOF-MS, protein bank and information
      technique. RESULTS: We analyzed the average maps and obtained 517 protein spots
      in the sub-healthy group and 535 protein spots in the control group. Between the
      sub-healthy group and the control group, the mean of 366 protein spots was
      matched, and the matching rate was 70.79%. Ten differential protein spots were
      screened by MALDI-TOF-MS, and 8 were identified. Five out of the 8 spots were
      significantly decreased, while 3 out of the 8 were significantly increased.
      CONCLUSION: The proteomic expression in colonic mucosa of people with shapeless
      stool is significantly different from that of healthy people. Eight differential
      proteins such as aldehyde dehydrogenase 1A1 isoform 1, 3-hydroxy-3-methylglutaryl
      coenzyme A synthase 2 (mitochondrial), gamma-actin, annexin A5 possibly involve
      in the pathogenesis of sub-healthy people with shapeless stool.

PMID- 21946202
TI  - [Association between cancer related fatigue  and social support in patients after
      breast cancer  chemotherapy in Changsha].
AB  - OBJECTIVE: To explore the association between the cancer related fatigue and
      social support in breast cancer patients after chemotherapy. METHODS: According
      to the uniform inclusive and exclusive criteria, 396 breast cancer patients after
      chemotherapy were sampled randomly from 4 hospitals in Changsha and investigated
      on the spot by cancer fatigue scale and social support scale. RESULTS: The levels
      of social support, subjective support, Objective support, and utilization of
      support of the breast cancer patients after chemotherapy were 36.63+/-7.80,
      21.05+/-4.67, 8.45+/-3.06, and 7.13+/-2.10, respectively, which were lower than
      the normal level, with significant difference(P<0.001). There was a negative
      correlation between each fatigue dimension and social support, subjective
      support, Objective support, and utilization of support (P<0.05 or P<0.001).
      CONCLUSION: The social support system in patients with breast cancer after
      chemotherapy is poor. There is a negative correlation between the social support
      system and cancer related fatigue.

PMID- 21946204
TI  - [Correlation between expression of HIF-2alpha and  OCT-4 and  prognosis of
      NSCLC].
AB  - OBJECTIVE: To investigate the expression and significance of hypoxia inducible
      factor-2alpha (HIF-2alpha) and transcription factor OCT-4 in non-small cell lung
      cancer (NSCLC), and evaluate their roles in the prognosis of NSCLC. METHODS:
      Tissues from 51 cases of NSCLC were collected and immunohistochemistry (SP
      method) was used to detect the expression of HIF-2alpha and OCT-4 proteins. The
      correlation between the protein expression and the prognosis of NSCLC was
      analyzed. RESULTS: The positive rates of HIF-2alpha and OCT-4 expression in the
      NSCLC were 52.9% and 72.5%, respectively. There was significant relation between
      the expression of HIF-2alpha and OCT-4 (r=0.514,P<0.01). High expression of them
      revealed poor prognosis for NSCLC patients characterized with a bad overall
      survival(P<0.05). CONCLUSION: There is a negative corelation between the
      expression of HIF-2alpha and OCT-4 and the prognosis of NSCLC. Combined
      examination of HIF-2alpha and OCT-4 expression might be an important biomarker
      for NSCLC prognosis.

PMID- 21946203
TI  - [Improvement of lower urinary tract symptoms  in patients with prostate cancer
      treated  with maximal androgen blockade].
AB  - OBJECTIVE: To investigate the timing of reaching maximum improvement of the lower
      urinary tract symptoms (LUTS) in patients with advanced prostate cancer treated
      with maximal androgen blockade(MAB), and to provide guidelines for the treatment
      program. METHODS: We collected the data of 45 advanced prostate cancer patients
      complicated with lower urinary tract symptoms who were treated by MAB. The
      international prostate symptom score (IPSS) and maximum urinary flow rate (Qmax)
      were selected as indicators reflecting the degree of lower urinary tract symptoms
      and were observed before the MAB, 3, 6, and 9 months after the patients received
      MAB. We also observed the changes of prostate volume and analyzed the role of MAB
      in improving LUTS in patients with prostate cancer. RESULTS: The IPSS and Qmax
      had significant difference between the 3rd month after the patients received MAB
      and before the MAB (P<0.05). No significant difference was found between the 3rd
      month and the 6th month after the patients received MAB (P>0.05). The prostate
      volume had significant difference in the 3rd month and the 6th month (P<0.05),
      but no significant difference in the 6th month and the 9th month (P>0.05).
      CONCLUSION: MAB for patients with advanced prostate cancer can improve their
      lower urinary tract symptoms, whose main effect is presented in the 3rd months
      after the androgen deprivation therapy.

PMID- 21946205
TI  - [Clinical analysis of 104 patients with hematological  malignancy after
      allogeneic hemotopoietic  stem cell transplantation].
AB  - OBJECTIVE: To study the efficacy of allogeneic hemotopoietic stem cell
      transplantation (allo-HSCT) for hematological malignancy. METHODS: A total of 104
      patients with hematological malignancy, who underwent allo-HSCT in Xiangya
      Hospital from December 1999 to January 2010, were retrospectively analyzed. Of
      the patients, the transplantation related mortality (TRM), relapse rate (RR), 5
      year overall survival (OS) and disease free survival (DFS) were estimated by
      Kaplan-Meier analysis. The unfavorable prognostic factors were also statistically
      examined. RESULTS: Hematopoietic reconstitution was achieved in 101 patients. At
      the last data of follow-up, the incidences of severe acute graft versus host
      disease (aGVHD) and extensive chronic GVHD were 15.38% and 25.53%, and the TRM
      and RR were 15.66% and 21.76%, respectively. The estimated 5-year OS and DFS for
      all patients were (73.49+/-4.59)% and (63.10+/-5.32)%, respectively. Those for
      acute myeloid leukemia (AML) patients were (63.00+/-9.51)% and (49.30+/-9.96)%,
      and those for chronic myeloid leukemia (CML) patients were (83.87+/-5.06)% and
      (74.55+/-6.79)%, respectively. The survival analysis suggested the poor
      prognostic factors for allo-HSCT recipients including female sex, severe aGVHD
      and refractory hematological malignancy. Further multivariate analyses revealed
      that severe aGVHD and refractory hematological malignancy were the independent
      risk factors of poor prognosis for the recipients (P<0.05). The 5-year DFS of
      severe aGVHD and refractory hematological malignancy patients was (48.22+/
      12.69)% and (42.09+/-12.31)%, respectively. The TRM of severe aGVHD, HLA
      mismatched graft and unrelated donor transplant was significantly higher than
      that of the corresponding control groups (57.14% vs. 4.81%, 33.33% vs. 10.41%,
      26.09% vs. 9.28%; P<0.05). The RR of refractory hematological malignancy was
      significantly higher than that of the control group (41.09% vs. 15.63%, P<0.05).
      CONCLUSION: The treatment of allo-HSCT can improve the disease free survival of
      patients with hematological malignany and is an important therapeutic method for
      hematological malignancy. Severe aGVHD and refractory hematological malignancy
      are the independent risk factors of poor prognosis for the allo-HSCT recipients
      with hematological malignancy.

PMID- 21946206
TI  - [Follow-up study on refractory schizophrenia  with brain stereotaxis therapy].
AB  - OBJECTIVE: To determine the long-term effect and security of refractory
      schizophrenia with brain stereotaxis multi-target therapy technique. METHODS: A
      total of 87 patients with refractory schizophrenia were treated with brain
      stereotaxis multi-target therapy and were followed up over 2 years. The scores of
      Clinical Global Impression, Brief Psychiatric Rating Scale, Positive and Negative
      Symptom Scale, Wechsler Adult Intelligence Scale, Wechsler Memory Scale, Actives
      of Daily Living, and Social Disability Screening Schedule were compared before
      and after the operation. RESULTS: Of the 87 patients, 40 obviously improved, 24
      improved, 12 improved little, 7 did not change. None grew worse, 1 died, and 3
      shed. There was a significant difference in the scales before and after the
      operation (P<0.01). No severe complications and sequelae occurred. CONCLUSION:
      Stereotaxic multi-target therapy is effective and safe for refractory
      schizophrenia. After the operation, drug therapy should be maintained and
      recovery of social function is helpful.

PMID- 21946207
TI  - [Expression and mechanism of osteoactivin in the kidney  of SD rats after acute
      cyclosporine A toxicity].
AB  - OBJECTIVE: To determine the expression and mechanism of osteoactivin (OA) in the
      kidney by establishing SD rat model of acute cyclosporine A (CsA) toxicity.
      METHODS: SD rats were fed with normal diet for a week, which they were then
      randomly divided into 3 groups: an experimental group (gavage with cycloporin A
      and olive oil), a vector group (gavage with olive oil), and a control group
      (gavage with normal saline). SD rats were killed 2 days, 1 week, or 2 weeks after
      the gavage to examine the serum creatinine (SCr) and body weight. HE staining was
      used to detect the kidney histopathological change. Immunohistochemistry was used
      to observe the staining degree and area of OA. Western blot was used to detect
      the OA protein.The mRNA expressions of the OA, matrix metalloproteinase-13(MMP
      13), and collagen type III(Col III) were examined by RT-PCR. RESULTS: The body
      weight and SCr of the rats in the experimental group 1 week and 2 days after the
      gavage had no significant difference compared with the vector group or the
      control group (P>0.05).On the end of 2nd week, the rats' body weight was
      significantly reduced, and SCr significantly increased compared with the vector
      group or the control group (P<0.001).The main histopathological changes in the
      experimental group were inflammatory cell infiltration, vacuolar degeneration of
      interstitial cells, or tubular epithelial cell necrosis. Intense OA expression
      located in the tubular epithelium and interstitial fibroblasts in the kidney of
      the experimental group was observed by immunohistochemistry. After CsA gavage,
      the relative mRNA expressions of OA, MMP-13, and Col III significantly increased
      with time. Western blot did not find the expression of OA protein in the control
      and the vector group, which increased with time in the experimental group.
      CONCLUSION: OA expresses in the kidney of SD rats after acute CsA toxicity and
      mainly expresses in the tubular epithelial cells and renal interstitium. OA is
      more sensitive to the damage of kidney tissue caused by CsA than by SCr. The
      early-phase up-regulation of OA expression in the tubular epithelium in response
      to renal injury caused by acute CsA toxicity might play a key role in triggering
      the renal interstitial fibrosis via activating expression of MMPs and collagen
      remodeling in SD rats.

PMID- 21946208
TI  - [Surgical management of vertebral sarcoidosis].
AB  - OBJECTIVE: To investigate the clinical characteristics, diagnostic foundation and
      treatment of vertebral sarcoidosis. METHODS: The clinical data of 13 patients
      with vertebral sarcoidosis who received anterior debridement and instrumentation
      were retrospectively analyzed. RESULTS: The onset of progressive pain in the
      pathological region was common in the 13 patients. Neurologic deficit existed in
      4 cases. Radiographic study showed multiple vertebral bone destructions, and no
      other systemic lesions were found. Surgical indications were progressive
      vertebral destruction, spinal instability or neurological deficit. Anterior
      vertebra resection, and autologous bone grafts fusion with internal fixation were
      done. No operative mortality and major complications occurred. Diagnosis was
      confirmed in all patients by pathological exam. After the surgery,
      metacortandracin treatment was given routinely for 1 year. Patients were followed
      up for 12-52 (median 26) months, and pain and neurological symptoms were
      alleviated. Visual analog scale (VAS) score was 7-10 (median 8) points
      preoperatively, which dropped to 0-4 (median 2) points postoperatively. All
      patients showed successful bone fusion with no recurrence. CONCLUSION: For
      vertebral sarcoidosis associated with progressive instability and/or neurological
      symptoms, surgical intervention combined with steroid therapy is safe and
      effective.

PMID- 21946209
TI  - [Photodynamic therapy for polypoidal  choroidal vasculopathy].
AB  - OBJECTIVE: To determine the effect of photodynamic therapy (PDT) for polypoidal
      choroidal vasculopathy (PCV). METHODS: Eleven patients (11 eyes) with PCV who
      were diagnosed by fundus fluorescein angiography (FFA), indocyanine green
      angiography (ICGA) and optic coherence tomography (OCT) were given PDT. The
      changes of best corrected visual acuity (BCVA), fundus photography, FFA and ICGA
      before and after the PDT were compared. Follow-up time varied from 6 to 30
      months. RESULTS: One month after the PDT, the BCVA was stable in 3 eyes,
      increased in 1 line in 3 eyes, increased in 2 lines in 2 eyes, and decreased in 2
      lines in 3 eyes. FFA and ICGA showed no leakage in 5 eyes, leakage reduced in 3
      eyes, and slight leakage in 3 eyes. At the last follow-up, the BCVA was stable in
      5 eyes, increased in 1 line in 2 eyes, increased in 2 lines in 2 eyes, and
      decreased in 2 lines in 2 eyes. FFA and ICGA showed no leakage in 6 eyes, leakage
      reduced in 3 eyes, and slight leakage in 2 eyes. No severe systemic or local
      adverse effect was found during or after the PDT, except that 1 eye had vitreous
      hemorrhage 2 months after the PDT. CONCLUSION: PDT may stop or reduce leakage of
      the lesion, facilitate the absorption of hemorrhage, edema and exudates, and
      stabilize or increase the patients' visual acuity. It could be a choice for PCV.

PMID- 21946210
TI  - [A attitude toward psychiatry among medical students].
AB  - OBJECTIVE: To explore the attitudes of medical students toward psychiatry.
      METHODS: A total of 254 fourth-year medical students were investigated with a 29
      item questionnaire. RESULTS: Although in general, medical school students showed
      a positive attitude towards psychiatry, opinions about certain aspects like the
      reputation of psychiatry and the attitude toward psychiatric therapy were not
      positive. CONCLUSION: There are still some misunderstandings for psychiatry among
      medical school students, some of which are based on false beliefs that should be
      actively targeted for remediation.

PMID- 21946211
TI  - [Chronic Helicobacter pylori infection induces the  proliferation and apoptosis
      in gastric epithelial cells  and gastric precancerosis in Mongolian gerbils].
AB  - OBJECTIVE: To explore the effect of different Helicobacter pylori (H.pylori)
      clinical strains on the proliferation and apoptosis of gastric epithelial cells,
      and to observe the effect of H.pylori on gastric mucosa by Mongolian gerbil model
      infected H.pylori. METHODS: H.pylori isolates harvested from pathologically
      documented gastric carcinoma (GC, n=10) or chronic gastritis specimens (CG, n=10)
      were co-cultured with GES-1 cells individually. MTT assay and flow cytometry were
      used to determine the proliferation and apoptosis of GES-1 cells induced by
      H.pylori isolates. Mongolian gerbils were infected by the most (A strain) and the
      least (B strain) significantly proliferated H.pylori strains. Results When co
      cultured with the cell/bacteria concentration ratio 1:1 and 1:50 for 12 h and the
      cell/bacteria concentration ratio 1:50 for 24 h, H.pylori clinical strains
      isolated from patients with gastric cancer promoted the proliferation of GES-1
      cells, and there was significant difference in the absorbance compared with the
      group of gastritis strains(P<0.05). The apoptosis rate of the GC and CG groups
      increased significantly (P<0.05) compared with the control group when co-cultured
      with the cell/bacteria concentration ratio 1:50 and 1:200, and there was no
      significant difference between the GC group and the CG group (P>0.05). The
      incidences of intestinal metaplasia and dysplasia in the A strain group were
      significantly higher than those in the B strain group (P<0.05). CONCLUSION:
      H.pylori strains from different disease sources have different effects on the
      proliferation of GES-1 cells. H.pylori isolated from gastric cancer can promote
      the proliferation of cells to different degrees and directly induce gastric
      precancerosis and gastric cancer.

PMID- 21946212
TI  - [Signaling of biglycan and cytokines in  bovine intervertebral disc cells].
AB  - OBJECTIVE: To evaluate the effect of biglycan on the signaling of cytokines
      (epidermal growth factor, osteogenic protein-1, and interleukin-1) in bovine
      intervertebral disc cells. METHODS: Nucleoplasty (NP) and annulus fibrosus (AF)
      cells of the intervertebral disc tissues were isolated from the tails of young
      adult bovine. First, the cells were treated in 3 ways: Biglycan alone, cytokines
      alone (epidermal growth factor, osteogenic protein-1, or interleukin-1), and
      biglycan combined with cytonkines. Western blot was used to observe the singling
      of biglycan and cytokines in bovine intervertebral disc cells, and to identify
      the effect of biglycan on cytokines mentioned above. RESULTS: Biglycan
      upregulated the signaling (3- 4 folds) with the optimal effect at 10 min and 20
      MUmol/L both in the AF cells and NP cells. Epidermal growth factor, osteogenic
      protein-1, or interleukin-1 also upregulated the protein expression in the
      extracellular matrix of intervertebral disc cells. When combined different
      biglycan concentrations with epidermal growth factor, osteogenic protein-1, or
      interleukin-1 to treat the intervertebral disc cells, the concentration of
      biglycan rose, whereas the cytokine signal decreased both in the bovine AF and NP
      cells (P<0.01). There was no significant difference between the AF and NP cells.
      CONCLUSION: Biglycan can adhere to the intervertebral disc cells to activate the
      extracellular signal-regulated kinase (ERK) pathway and this effect is time and
      concentration dependent. Byglycan can decrease not only the anabolism effect of
      epidermal growth factor and osteogenic protein-1, but also the catabolism effect
      of interleukin-1. This regulatory role of biglycan may be very important to
      maintain the metabolism balance. Biglycan may be good for the repair of
      intervertebral disc.

PMID- 21946213
TI  - Autophagy is involved in the early step of Japanese encephalitis virus infection.
AB  - Japanese encephalitis virus (JEV), an enveloped Flavivirus with a positive-sense
      RNA genome, causes acute encephalitis with high mortality in humans. We used a
      virulent (RP-9) and an attenuated (RP-2ms) JEV strain to assess the role of
      autophagy in JEV infection. By monitoring the levels of lipidated LC3, we found
      that autophagy was induced in human NT-2 cells infected with RP-2ms, especially
      at the late stage, and to a lesser extent with RP-9. The induction of autophagy
      by rapamycin increased viral production, whereas the inhibition of autophagy by 3
      methyladenine reduced viral yields for both RP-9 and RP-2ms. The viral
      replication of RP-9 and RP-2ms was also reduced in cells with downregulated ATG5
      or Beclin 1 expression, suggesting a proviral role of autophagy in JEV
      replication. To determine the step of JEV life cycle affected by autophagy, we
      used an mCherry-LC3 fusion protein as the autophagosome marker. Little of no
      colocalization of LC3 puncta with dsRNA was noted, whereas the input JEV
      particles were targeted to autophagosomes stained positive for early endosome
      marker. Overall, we show for the first time that the cellular autophagy process
      is involved in JEV infection and the inoculated viral particles traffic to
      autophagosomes for subsequent steps of viral infection.

PMID- 21946214
TI  - Low molecular weight heparin downregulates tissue factor expression and activity
      by modulating growth factor receptor-mediated induction of nuclear factor-kappaB.
AB  - Treatment of cancer patients with low molecular weight heparin (LMWH) appears to
      have beneficial effects. In this study, the influence of low molecular weight
      heparin (LMWH) on tissue factor (TF) expression and activity in five cell lines
      from various tissues was analysed and explored. Incubation of cells with LMWH (0
      2000MUg/ml) resulted in the downregulation of TF mRNA expression which was both
      LMWH concentration-dependent and time-dependent. Downregulation of TF was also
      measured as decreased cellular TF antigen and activity. Consistently, incubation
      of cells with LMWH suppressed the nuclear localisation and the transcriptional
      activity of NFkappaB. Decreased TF mRNA was largely achievable by incubating the
      cells with an NFkappaB inhibitor alone whilst incubation with betulinic acid to
      activate NFkappaB reversed the inhibitory influence of LMWH. Cells were also
      incubated with a range of concentrations of EGF (0-10ng/ml), bFGF (0-20ng/ml) or
      VEGF (0-4ng/ml) in the presence or absence of LMWH (200MUg/ml) for 24h and TF
      antigen measured. Inclusion of LMWH reduced TF expression in response to EGF,
      bFGF or VEGF but TF expression was partially restored by increasing
      concentrations of the growth factors. We conclude that LMWH downregulates TF
      expression in vitro through a mechanism that involves interference with the
      function of growth factors which in turn is mediated through the downregulation
      of the transcriptional activity of NFkappaB. This mechanism may also explain some
      of the beneficial influences attributed to LMWH therapy in the treatment of
      cancer patients.

PMID- 21946216
TI  - Comparative effectiveness research: relative and efficient outcomes in surgery
      patients.

PMID- 21946215
TI  - Molecular properties of TAR DNA binding protein-43 fragments are dependent upon
      its cleavage site.
AB  - Aggregation of TAR DNA binding protein-43 (TDP-43) is a hallmark feature of
      amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Under
      pathogenic conditions, abnormal cleavage of TDP-43 produces the phosphorylated C
      terminal fragments (CTFs), which are enriched in neuronal inclusions; however,
      molecular properties of those TDP-43 fragments remain to be characterized. Here
      we show distinct degrees of solubility and phosphorylation among fragments
      truncated at different sites of TDP-43. Truncations were tested mainly within a
      second RNA recognition motif (RRM2) of TDP-43; when the truncation site was more
      C-terminal in an RRM2 domain, a TDP-43 CTF basically became less soluble and more
      phosphorylated in differentiated Neuro2a cells. We also found that cleavage at
      the third beta-strand in RRM2 leads to the formation of SDS-resistant soluble
      oligomers. Molecular properties of TDP-43 fragments thus significantly depend
      upon its cleavage site, which might reflect distinct molecular pathologies among
      sub-types of TDP-43 proteinopathies.

PMID- 21946217
TI  - Distress and career satisfaction among 14 surgical specialties, comparing
      academic and private practice settings.
AB  - OBJECTIVE(S): We compared distress parameters and career satisfaction from survey
      results of surgeons from 14 specialties practicing in an academic versus private
      practice environment. METHODS: The 2008 American College of Surgeons survey
      evaluated demographic variables, practice characteristics, career satisfaction,
      and distress parameters using validated instruments. RESULTS: The practice
      setting (academic vs. private practice) was independently associated with burnout
      in a multivariate (MV) analysis (odds ratio [OR] 1.172, P = 0.02). Academic
      surgeons were less likely to experience burnout compared to those in private
      practice (37.7% vs. 43.1%), less likely to screen positive for depression (27.6%
      vs. 33%) or to have suicide ideation (4.7% vs. 7.4%; all P < 0.0001). They were
      also more likely to have career satisfaction (77.4% of academic surgeons would
      become a surgeon again vs. 64.9% for those in private practice; P < 0.0001)) and
      to recommend a medical career to their children (61.3% vs. 43.7%, P < 0.0001).
      For academic surgeons, the most significant positive associations with burnout
      were: (1) trauma surgery (OR 1.513, P = 0.0059), (2) nights on call (OR 1.062, P
      = 0.0123), and (3) hours worked (OR 1.019, P < 0.0001), whereas the negative
      associations were: (1) having older children (>22 years; OR 0.529, P < 0.0001),
      (2) pediatric surgery (OR 0.583, P = 0.0053), (3) cardiothoracic surgery (OR
      0.626, P = 0.0117), and (4) being male (OR 0.787, P = 0.0491). In a private
      practice setting, the most significant positive associations with burnout were:
      (1) urologic surgery (OR 1.497, P = 0.0086), (2) having 31% to 50% time for
      nonclinical activities (OR 1.404, P = 0.0409), (3) incentive based pay (OR 1.344,
      P < 0.0001), (4) nights on call (OR 1.045, P = 0.0029), and (5) hours worked (OR
      1.015, P < 0.0001), whereas the negative associations were: (1) older children
      (OR 0.677, P = 0.0001), (2) physician spouse (OR 0.753, P = 0.0093), and (3)
      older age (OR 0.989, P = 0.0158). The independent factors relating to career
      satisfaction for surgeons in private practice and academic practice were also
      different. CONCLUSIONS: Factors associated with burnout were distinct for
      academic and private practice surgeons. Distress parameters were lower and career
      satisfaction higher for academic surgeons.

PMID- 21946218
TI  - Single incision versus standard 3-port laparoscopic appendectomy: a prospective
      randomized trial.
AB  - BACKGROUND: Laparoscopic appendectomy through a single umbilical incision is an
      emerging approach supported by several case series. However, to date, prospective
      comparative data are lacking. Therefore, we conducted a prospective, randomized
      trial comparing single site umbilical laparoscopic appendectomy to 3-port
      laparoscopic appendectomy. METHODS: After Internal Review Board approval,
      patients were randomized to laparoscopic appendectomy via a single umbilical
      incision or standard 3-port access. The primary outcome variable was
      postoperative wound infection. Using a power of 0.9 and an alpha of 0.05, 180
      patients were calculated for each arm. Patients with perforated appendicitis were
      excluded. The technique of ligation/division of the appendix and mesoappendix was
      left to the surgeon's discretion. There were 7 participating surgeons dictated by
      the call schedule. All patients received the same preoperative antibiotics and
      postoperative management was controlled. RESULTS: There were 360 patients were
      enrolled between August 2009 and November 2010. There were no differences in
      patient characteristics at presentation. There was no difference in wound
      infection rate, time to regular diet, length of hospitalization, or time to
      return to full activity. Operative time, doses of narcotics, surgical difficultly
      and hospital charges were greater with the single site approach. Also, the mean
      operative time was 5 minutes longer for the single site group. CONCLUSION: The
      single site umbilical laparoscopic approach to appendectomy produces longer
      operative times resulting in greater charges. However, these small differences
      are likely of marginal clinical relevance. The study was registered with
      clinicaltrials.gov at the inception of enrollment (NCT00981136).

PMID- 21946219
TI  - Minimally invasive mitral valve surgery expands the surgical options for high
      risks patients.
AB  - BACKGROUND: A simplified minimally invasive mitral valve surgery (MIMVS) approach
      avoiding cross-clamping and cardioplegic myocardial arrest using a small (5 cm)
      right antero-lateral incision was developed. We hypothesized that, in high-risk
      patients and in patients with prior sternotomy, this approach would yield
      superior results compared to those predicted by the Society of Thoracic Surgeons
      (STS) algorithm for standard median sternotomy mitral valve surgery. METHODS:
      Five hundred and four consecutive patients (249 males/255 females), median age 65
      years (range 20-92 years) underwent MIMVS between 1/06 and 8/09. Median
      preoperative New York Heart Association function class was 3 (range 1-4). Eighty
      two (16%) patients had an ejection fraction <=35%. Forty-seven (9%) had a STS
      predicted mortality >=10%. Under cold fibrillatory arrest (median temperature 28
      degrees C) without aortic cross-clamp, mitral valve repair (224/504, 44%) or
      replacement (280/504, 56%) was performed. RESULTS: Thirty-day mortality for the
      entire cohort was 2.2% (11/504). In patients with a STS predicted mortality >=
      10% (range 10%-67%), the observed 30-day mortality was 4% (2/47), lower than the
      mean STS predicted mortality of 20%. Morbidity in this high-risk group was
      equally low: 1 of 47 (2%) patients underwent reexploration for bleeding, 1 of 47
      (2%) patients suffered a permanent neurologic deficit, none had wound infection.
      The median length of stay was 8 days (range 1-68 days). CONCLUSIONS: This study
      demonstrates that MIMVS without aortic cross-clamp is reproducible with low
      mortality and morbidity rates. This approach expands the surgical options for
      high-risk patients and yields to superior results than the conventional median
      sternotomy approach.

PMID- 21946221
TI  - Albumin as a marker of nutrition:  a common pitfall.

PMID- 21946223
TI  - What is the optimal blood glucose range to improve morbidity and mortality in
      surgical patients?

PMID- 21946226
TI  - Study of cerebral gene expression densities using Voronoi analysis.
AB  - As the available public cerebral gene expression image data increasingly grows,
      the demand for automated methods to analyze such large amount of data also
      increases. An important study that can be carried out on these data is related to
      the spatial relationship between gene expressions. Similar spatial density
      distribution of expression between genes may indicate they are functionally
      correlated, thus the identification of these similarities is useful in suggesting
      directions of investigation to discover gene interactions and their correlated
      functions. In this paper, we describe the use of a high-throughput methodology
      based on Voronoi diagrams to automatically analyze and search for possible local
      spatial density relationships between gene expression images. We tested this
      method using mouse brain section images from the Allen Mouse Brain Atlas public
      database. This methodology provided measurements able to characterize the
      similarity of the density distribution between gene expressions and allowed the
      visualization of the results through networks and Principal Component Analysis
      (PCA). These visualizations are useful to analyze the similarity level between
      gene expression patterns, as well as to compare connection patterns between
      region networks. Some genes were found to have the same type of function and to
      be near each other in the PCA visualizations. These results suggest cerebral
      density correlations between gene expressions that could be further explored.

PMID- 21946229
TI  - Effects of body mass index on step count accuracy of physical activity monitors.
AB  - BACKGROUND: Activity monitors are widely used in research, and are currently
      being used to study physical activity (PA) trends in the US and Canada. The
      purpose of this study was to determine if body mass index (BMI) affects the step
      count accuracy of commonly used accelerometer-based activity monitors during
      treadmill walking. METHODS: Participants were classified into BMI categories and
      instructed to walk on a treadmill at 3 different speeds (40, 67, and 94 m.min(
      1)) while wearing 4 accelerometer-based activity monitors (ActiGraph GT1M,
      ActiCal, NL-2000, and StepWatch). RESULTS: There was no significant main effect
      of BMI on pedometer accuracy. At the slowest speed, all waist-mounted devices
      significantly underestimated actual steps (P < .001), with the NL-2000 recording
      the greatest percentage (72%). At the intermediate speed, the ActiGraph was the
      least accurate, recording only 80% of actual steps. At the fastest speed, all of
      the activity monitors demonstrated a high level of accuracy. CONCLUSION: Our data
      suggest that BMI does not greatly affect the step-counting accuracy of
      accelerometer-based activity monitors. However, the accuracy of the ActiGraph,
      ActiCal, and NL-2000 decreases at slower speeds. The ankle-mounted StepWatch was
      the most accurate device across a wide range of walking speeds.

PMID- 21946227
TI  - High-resolution detection of 13C multiplets from the conscious mouse brain by ex
      vivo NMR spectroscopy.
AB  - Glucose readily supplies the brain with the majority of carbon needed to sustain
      neurotransmitter production and utilization. The rate of brain glucose metabolism
      can be computed using (13)C nuclear magnetic resonance (NMR) spectroscopy by
      detecting changes in (13)C contents of products generated by cerebral metabolism.
      As previously observed, scalar coupling between adjacent (13)C carbons
      (multiplets) can provide additional information to (13)C contents for the
      computation of metabolic rates. Most NMR studies have been conducted in large
      animals (often under anesthesia) because the mass of the target organ is a
      limiting factor for NMR. Yet, despite the challengingly small size of the mouse
      brain, NMR studies are highly desirable because the mouse constitutes a common
      animal model for human neurological disorders. We have developed a method for the
      ex vivo resolution of NMR multiplets arising from the brain of an awake mouse
      after the infusion of [1,6-(13)C(2)]glucose. NMR spectra obtained by this method
      display favorable signal-to-noise ratios. With this infusion protocol, the (13)C
      multiplets of glutamate, glutamine, GABA and aspartate achieved steady state
      after 150 min. The method enables the accurate resolution of multiplets over time
      in the awake mouse brain. We anticipate that this method can be broadly
      applicable to compute brain fluxes in normal and transgenic mouse models of
      neurological disorders.

PMID- 21946230
TI  - The prognostic significance of percentage of tumour involvement according to
      disease risk group in men treated with radical prostatectomy.
AB  - We investigated the prognostic significance of percentage of tumour involvement
      (PTI) according to the clinicopathological features of prostate cancer among
      patients who underwent radical prostatectomy (RP). A retrospective study of 534
      patients who underwent RP between September 2003 and March 2008 without any
      neoadjuvant or adjuvant therapy was performed. The associations of PTI with
      various clinicopathological features and biochemical recurrence-free survival
      were examined via uni- and multivariate analyses. The predictive accuracy of the
      multivariate model was assessed with a receiver operating characteristics-derived
      area under the curve. PTI was demonstrated to be significantly associated with
      preoperative prostate-specific antigen (PSA) level (P=0.001), pathological
      Gleason score (P<0.001), extraprostatic tumour extension (P<0.001), seminal
      vesicle invasion (P<0.001) and positive surgical margin (P<0.001) in univariate
      analyses. When patients were stratified into disease risk groups, PTI was an
      independent predictor of biochemical recurrence-free survival in multivariate
      analysis only among the low-risk group (P=0.033) but not the intermediate-
      (P=0.287) or the high-risk groups (P=0.828). The addition of the PTI did not
      significantly increase the accuracy of the multivariate model devised for the
      prediction of biochemical recurrence-free survival among both total patients
      (P=0.459) and the low-risk group (P=0.268), respectively. In conclusion, although
      PTI appeared to be a more significant prognostic factor among patients with low
      risk disease than among those with higher risk diseases, overall, the PTI may not
      provide additional prognostic information beyond what can already be obtained via
      established prognostic factors.

PMID- 21946231
TI  - What controls PTEN and what it controls (in prostate cancer).

PMID- 21946232
TI  - Binding properties of ferrocene-glutathione conjugates as inhibitors and sensors
      for glutathione S-transferases.
AB  - The binding properties of two electroactive glutathione-ferrocene conjugates that
      consist in glutathione attached to one or both of the cyclopentadienyl rings of
      ferrocene (GSFc and GSFcSG), to Schistosoma japonica glutathione S-transferase
      (SjGST) were studied by spectroscopy fluorescence, isothermal titration
      calorimetry (ITC) and differential pulse voltammetry (DPV). Such ferrocene
      conjugates resulted to be competitive inhibitors of glutathione S-transferase
      with an increased binding affinity relative to the natural substrate glutathione
      (GSH). We found that the conjugate having two glutathione units (GSFcSG) exhibits
      an affinity for SjGST approximately two orders of magnitude higher than GSH.
      Furthermore, it shows negative cooperativity with the affinity for the second
      binding site two orders of magnitude lower than that for the first one. We
      propose that the reason for such negative cooperativity is steric since, i) the
      obtained thermodynamic parameters do not indicate profound conformational changes
      upon GSFcSG binding and ii) docking studies have shown that, when bound, part of
      the first bound ligand invades the second site due to its large size. In
      addition, voltammetric measurements show a strong decrease of the peak current
      upon binding of ferrocene-glutathione conjugates to SjGST and provide very
      similar K values than those obtained by ITC. Moreover, the sensing ability,
      expressed by the sensitivity parameter shows that GSFcSG is much more sensitive
      than GSFc, for the detection of SjGST.

PMID- 21946233
TI  - Catalogue of alleles of gliadin-coding loci in durum wheat (Triticum durum
      Desf.).
AB  - Gliadins are seed storage proteins which are characterized by high intervarietal
      polymorphism and can be used as genetic markers. As a result of our work, a
      considerably extended catalogue of allelic variants of gliadin component blocks
      was compiled for durum wheat; 74 allelic variants for four gliadin-coding loci
      were identified for the first time. The extended catalogue includes a total of
      131 allelic variants: 16 for locus Gli-A1(d), 19 for locus Gli-B1(d), 41 for
      locus Gli-A2(d), and 55 for locus Gli-B2(d). The electrophoretic pattern of the
      standard cultivar and a diagram are provided for every block identified. The
      number of alleles per family is quite small for loci Gli-A1(d) and Gli-B1(d) of
      durum wheat, as contrasted to loci Gli-A2(d) and Gli-B2(d) that are characterized
      by large families including many alleles. The presence of large block families
      determines a higher diversity of durum wheat for loci Gli-A2(d) and Gli-B2(d) as
      compared to Gli-A1(d) and Gli-B1(d). The catalogue of allelic variants of gliadin
      component blocks can be used by seed farmers to identify durum wheat cultivars
      and evaluate their purity; by breeders, to obtain homogenous cultivars and
      control the initial stages of selection; by gene bank experts, to preserve native
      varieties and the original biotypic composition of cultivars.

PMID- 21946234
TI  - RhoA-ROCK-Myosin pathway regulates morphological plasticity of cultured olfactory
      ensheathing cells.
AB  - Olfactory ensheathing cells (OECs) are glial cells in the olfactory system with
      morphological and functional plasticity. Cultured OECs have the flattened and
      process-bearing shape. Reversible changes have been found between these two
      morphological phenotypes. However, the molecular mechanism underlying the
      regulation of their morphological plasticity remains elusive. Using RhoA FRET
      biosensor, we found that the active RhoA signal mainly distributed in the
      lamellipodia and/or filopodia of OECs. Local disruption of these active RhoA
      distributions led to the morphological change from the flattened into process
      bearing shape and promoted process outgrowth. Furthermore, RhoA pathway
      inhibitors, Toxin-B, C3, Y-27632 or over-expression of DN-RhoA blocked serum
      induced morphological change of OECs from the process-bearing into flattened
      shape, whereas the activation of RhoA pathway by lysophosphatidic acid (LPA)
      promoted the morphological change from the process-bearing into flattened shape.
      Finally, ROCK-Myosin-F-actin as a downstream of RhoA pathway was involved in
      morphological plasticity of OECs. Taken together, these results suggest that RhoA
      ROCK-Myosin pathway mediates the morphological plasticity of cultured OECs in
      response to extracellular cues.

PMID- 21946235
TI  - Search filters to identify geriatric medicine in Medline.
AB  - OBJECTIVES: To create user-friendly search filters with high sensitivity,
      specificity, and precision to identify articles on geriatric medicine in Medline.
      DESIGN: A diagnostic test assessment framework was used. A reference set of 2255
      articles was created by hand-searching 22 biomedical journals in Medline, and
      each article was labeled as 'relevant', 'not relevant', or 'possibly relevant'
      for geriatric medicine. From the relevant articles, search terms were identified
      to compile different search strategies. The articles retrieved by the various
      search strategies were compared with articles from the reference set as the index
      test to create the search filters. MEASURES: Sensitivity, specificity, precision,
      accuracy, and number-needed-to-read (NNR) were calculated by comparing the
      results retrieved by the different search strategies with the reference set.
      RESULTS: The most sensitive search filter had a sensitivity of 94.8%, a
      specificity of 88.7%, a precision of 73.0%, and an accuracy of 90.2%. It had an
      NNR of 1.37. The most specific search filter had a specificity of 96.6%, a
      sensitivity of 69.1%, a precision of 86.6%, and an accuracy of 89.9%. It had an
      NNR of 1.15. CONCLUSION: These geriatric search filters simplify searching for
      relevant literature and therefore contribute to better evidence-based practice.
      The filters are useful to both the clinician who wants to find a quick answer to
      a clinical question and the researcher who wants to find as many relevant
      articles as possible without retrieving too many irrelevant articles.

PMID- 21946236
TI  - A systematic review of the psychological literature on interruption and its
      patient safety implications.
AB  - OBJECTIVE: To understand the complex effects of interruption in healthcare.
      MATERIALS AND METHODS: As interruptions have been well studied in other domains,
      the authors undertook a systematic review of experimental studies in psychology
      and human-computer interaction to identify the task types and variables
      influencing interruption effects. RESULTS: 63 studies were identified from 812
      articles retrieved by systematic searches. On the basis of interruption profiles
      for generic tasks, it was found that clinical tasks can be distinguished into
      three broad types: procedural, problem-solving, and decision-making. Twelve
      experimental variables that influence interruption effects were identified. Of
      these, six are the most important, based on the number of studies and because of
      their centrality to interruption effects, including working memory load,
      interruption position, similarity, modality, handling strategies, and practice
      effect. The variables are explained by three main theoretical frameworks: the
      activation-based goal memory model, prospective memory, and multiple resource
      theory. DISCUSSION: This review provides a useful starting point for a more
      comprehensive examination of interruptions potentially leading to an improved
      understanding about the impact of this phenomenon on patient safety and task
      efficiency. The authors provide some recommendations to counter interruption
      effects. CONCLUSION: The effects of interruption are the outcome of a complex set
      of variables and should not be considered as uniformly predictable or bad. The
      task types, variables, and theories should help us better to identify which
      clinical tasks and contexts are most susceptible and assist in the design of
      information systems and processes that are resilient to interruption.

PMID- 21946237
TI  - The design and implementation of an open-source, data-driven cohort recruitment
      system: the Duke Integrated Subject Cohort and Enrollment Research Network
      (DISCERN).
AB  - OBJECTIVE: Failure to reach research subject recruitment goals is a significant
      impediment to the success of many clinical trials. Implementation of health
      information technology has allowed retrospective analysis of data for cohort
      identification and recruitment, but few institutions have also leveraged real
      time streams to support such activities. DESIGN: Duke Medicine has deployed a
      hybrid solution, The Duke Integrated Subject Cohort and Enrollment Research
      Network (DISCERN), that combines both retrospective warehouse data and clinical
      events contained in prospective Health Level 7 (HL7) messages to immediately
      alert study personnel of potential recruits as they become eligible. RESULTS:
      DISCERN analyzes more than 500000 messages daily in service of 12 projects. Users
      may receive results via email, text pages, or on-demand reports. Preliminary
      results suggest DISCERN's unique ability to reason over both retrospective and
      real-time data increases study enrollment rates while reducing the time required
      to complete recruitment-related tasks. The authors have introduced a
      preconfigured DISCERN function as a self-service feature for users. LIMITATIONS:
      The DISCERN framework is adoptable primarily by organizations using both HL7
      message streams and a data warehouse. More efficient recruitment may exacerbate
      competition for research subjects, and investigators uncomfortable with new
      technology may find themselves at a competitive disadvantage in recruitment.
      CONCLUSION: DISCERN's hybrid framework for identifying real-time clinical events
      housed in HL7 messages complements the traditional approach of using
      retrospective warehoused data. DISCERN is helpful in instances when the required
      clinical data may not be loaded into the warehouse and thus must be captured
      contemporaneously during patient care. Use of an open-source tool supports
      generalizability to other institutions at minimal cost.

PMID- 21946238
TI  - Facilitating adverse drug event detection in pharmacovigilance databases using
      molecular structure similarity: application to rhabdomyolysis.
AB  - BACKGROUND: Adverse drug events (ADE) cause considerable harm to patients, and
      consequently their detection is critical for patient safety. The US Food and Drug
      Administration maintains an adverse event reporting system (AERS) to facilitate
      the detection of ADE in drugs. Various data mining approaches have been developed
      that use AERS to detect signals identifying associations between drugs and ADE.
      The signals must then be monitored further by domain experts, which is a time
      consuming task. OBJECTIVE: To develop a new methodology that combines existing
      data mining algorithms with chemical information by analysis of molecular
      fingerprints to enhance initial ADE signals generated from AERS, and to provide a
      decision support mechanism to facilitate the identification of novel adverse
      events. RESULTS: The method achieved a significant improvement in precision in
      identifying known ADE, and a more than twofold signal enhancement when applied to
      the ADE rhabdomyolysis. The simplicity of the method assists in highlighting the
      etiology of the ADE by identifying structurally similar drugs. A set of drugs
      with strong evidence from both AERS and molecular fingerprint-based modeling is
      constructed for further analysis. CONCLUSION: The results demonstrate that the
      proposed methodology could be used as a pharmacovigilance decision support tool
      to facilitate ADE detection.

PMID- 21946239
TI  - Prescribers' expectations and barriers to electronic prescribing of controlled
      substances.
AB  - OBJECTIVE: To better understand barriers associated with the adoption and use of
      electronic prescribing of controlled substances (EPCS), a practice recently
      established by US Drug Enforcement Administration regulation. MATERIALS AND
      METHODS: Prescribers of controlled substances affiliated with a regional health
      system were surveyed regarding current electronic prescribing (e-prescribing)
      activities, current prescribing of controlled substances, and expectations and
      barriers to the adoption of EPCS. RESULTS: 246 prescribers (response rate of 64%)
      represented a range of medical specialties, with 43.1% of these prescribers
      current users of e-prescribing for non-controlled substances. Reported issues
      with controlled substances included errors, pharmacy call-backs, and diversion;
      most prescribers expected EPCS to address many of these problems, specifically
      reduce medical errors, improve work flow and efficiency of practice, help
      identify prescription diversion or misuse, and improve patient treatment
      management. Prescribers expected, however, that it would be disruptive to
      practice, and over one-third of respondents reported that carrying a security
      authentication token at all times would be so burdensome as to discourage
      adoption. DISCUSSION: Although adoption of e-prescribing has been shown to
      dramatically reduce medication errors, challenges to efficient processes and
      errors still persist from the perspective of the prescriber, that may interfere
      with the adoption of EPCS. Most prescribers regarded EPCS security measures as a
      small or moderate inconvenience (other than carrying a security token), with
      advantages outweighing the burden. CONCLUSION: Prescribers are optimistic about
      the potential for EPCS to improve practice, but view certain security measures as
      a burden and potential barrier.

PMID- 21946240
TI  - Developing a natural language processing application for measuring the quality of
      colonoscopy procedures.
AB  - OBJECTIVE: The quality of colonoscopy procedures for colorectal cancer screening
      is often inadequate and varies widely among physicians. Routine measurement of
      quality is limited by the costs of manual review of free-text patient charts. Our
      goal was to develop a natural language processing (NLP) application to measure
      colonoscopy quality. MATERIALS AND METHODS: Using a set of quality measures
      published by physician specialty societies, we implemented an NLP engine that
      extracts 21 variables for 19 quality measures from free-text colonoscopy and
      pathology reports. We evaluated the performance of the NLP engine on a test set
      of 453 colonoscopy reports and 226 pathology reports, considering accuracy in
      extracting the values of the target variables from text, and the reliability of
      the outcomes of the quality measures as computed from the NLP-extracted
      information. RESULTS: The average accuracy of the NLP engine over all variables
      was 0.89 (range: 0.62-1.0) and the average F measure over all variables was 0.74
      (range: 0.49-0.89). The average agreement score, measured as Cohen's kappa,
      between the manually established and NLP-derived outcomes of the quality measures
      was 0.62 (range: 0.09-0.86). DISCUSSION: For nine of the 19 colonoscopy quality
      measures, the agreement score was 0.70 or above, which we consider a sufficient
      score for the NLP-derived outcomes of these measures to be practically useful for
      quality measurement. CONCLUSION: The use of NLP for information extraction from
      free-text colonoscopy and pathology reports creates opportunities for large
      scale, routine quality measurement, which can support quality improvement in
      colonoscopy care.

PMID- 21946241
TI  - Development and preliminary evidence for the validity of an instrument assessing
      implementation of human-factors principles in medication-related decision-support
      systems--I-MeDeSA.
AB  - BACKGROUND: Medication-related decision support can reduce the frequency of
      preventable adverse drug events. However, the design of current medication alerts
      often results in alert fatigue and high over-ride rates, thus reducing any
      potential benefits. METHODS: The authors previously reviewed human-factors
      principles for relevance to medication-related decision support alerts. In this
      study, instrument items were developed for assessing the appropriate
      implementation of these human-factors principles in drug-drug interaction (DDI)
      alerts. User feedback regarding nine electronic medical records was considered
      during the development process. Content validity, construct validity through
      correlation analysis, and inter-rater reliability were assessed. RESULTS: The
      final version of the instrument included 26 items associated with nine human
      factors principles. Content validation on three systems resulted in the addition
      of one principle (Corrective Actions) to the instrument and the elimination of
      eight items. Additionally, the wording of eight items was altered. Correlation
      analysis suggests a direct relationship between system age and performance of DDI
      alerts (p=0.0016). Inter-rater reliability indicated substantial agreement
      between raters (kappa=0.764). CONCLUSION: The authors developed and gathered
      preliminary evidence for the validity of an instrument that measures the
      appropriate use of human-factors principles in the design and display of DDI
      alerts. Designers of DDI alerts may use the instrument to improve usability and
      increase user acceptance of medication alerts, and organizations selecting an
      electronic medical record may find the instrument helpful in meeting their
      clinicians' usability needs.

PMID- 21946242
TI  - Drug side effect extraction from clinical narratives of psychiatry and psychology
      patients.
AB  - OBJECTIVE: To extract physician-asserted drug side effects from electronic
      medical record clinical narratives. MATERIALS AND METHODS: Pattern matching rules
      were manually developed through examining keywords and expression patterns of
      side effects to discover an individual side effect and causative drug
      relationship. A combination of machine learning (C4.5) using side effect keyword
      features and pattern matching rules was used to extract sentences that contain
      side effect and causative drug pairs, enabling the system to discover most side
      effect occurrences. Our system was implemented as a module within the clinical
      Text Analysis and Knowledge Extraction System. RESULTS: The system was tested in
      the domain of psychiatry and psychology. The rule-based system extracting side
      effects and causative drugs produced an F score of 0.80 (0.55 excluding allergy
      section). The hybrid system identifying side effect sentences had an F score of
      0.75 (0.56 excluding allergy section) but covered more side effect and causative
      drug pairs than individual side effect extraction. DISCUSSION: The rule-based
      system was able to identify most side effects expressed by clear indication
      words. More sophisticated semantic processing is required to handle complex side
      effect descriptions in the narrative. We demonstrated that our system can be
      trained to identify sentences with complex side effect descriptions that can be
      submitted to a human expert for further abstraction. CONCLUSION: Our system was
      able to extract most physician-asserted drug side effects. It can be used in
      either an automated mode for side effect extraction or semi-automated mode to
      identify side effect sentences that can significantly simplify abstraction by a
      human expert.

PMID- 21946244
TI  - Reconceptualizing in a dual-system model the effects of prenatal cocaine exposure
      on adolescent development: a short review.
AB  - The mechanisms of long-term effects of prenatal cocaine exposure (PCE) and
      consequent elevated impulsivity during adolescence are poorly understood. In this
      review, the development-programmed neural maturation is summarized to highlight
      adolescence as another critical period of brain development. We further
      synthesize maladaptation of the dopamine (DA) system, hypothalamic-pituitary
      adrenal-axis (HPA-axis) and pathological interactions between these two systems
      originating from previous fetal programming into a dual-system model to explain
      insufficient behavioral inhibition in affected adolescents.

PMID- 21946245
TI  - The management of primary central nervous system lymphoma related to AIDS in the
      HAART era.
AB  - PURPOSE OF REVIEW: The review highlights the recent advances in the pathogenesis,
      diagnosis and treatment of AIDS-related primary CNS lymphoma (AIDS-PCNSL). RECENT
      FINDINGS: The incidence of AIDS-PCNSL has decreased in the era of highly active
      antiretroviral therapy (HAART). The prognosis has improved and this most probably
      in relation both with the HAART-induced immunologic status recovery and
      subsequently the possibility to use more aggressive treatment strategies.
      Immunomodulatory effect of HAART seems also to have an indirect antitumor
      activity on the disease. SUMMARY: The treatment strategy for AIDS-PCNSL in the
      HAART era tends to become similar to that of the immunocompetent population. In
      the absence of randomized trials devoted to AIDS-PCNSL, most current national
      comprehensive cancer network guidelines recommend the use of high-dose
      methotrexate-based chemotherapy combined or not with whole-brain radiotherapy as
      initial treatment in addition to HAART. The objective for the future would be
      that prognosis of AIDS-PCNSL catch up with that of the immunocompetent patients
      with special attention to systemic and neurocognitive tolerance of the
      treatments.

PMID- 21946247
TI  - Unravelling the epigenomic dimension of breast cancers.
AB  - PURPOSE OF REVIEW: Breast cancer remains the first cause of cancer-related
      mortality in women. This can be explained by the high histological and molecular
      heterogeneity of the disease, making it hard to choose a therapy adapted to each
      patient. Over this last year, several groups have evaluated the epigenetic
      component of breast cancer, as epigenetics appears to be important in
      carcinogenesis. Results suggest that assessing the epigenetic aspects of breast
      tumours could strongly improve our understanding of the biology and heterogeneity
      of breast cancers. RECENT FINDINGS: The heterogeneity of breast tumours described
      at the histological and transcriptional levels exists also at the epigenetic
      level. DNA methylation profiles both confirm previous observations based on
      histological and transcriptomic analyses and add new levels of complexity to the
      picture. Several methylation signatures have been evidenced, that can stratify
      patients in terms of prognosis. DNA methylation profiles could also be a marker
      of lineage restriction, reflecting the cell type from which a tumour originates.
      SUMMARY: While focusing mainly on gene promoters and CpG islands, the genome
      scale DNA methylation profiling studies, conducted last year, highlighted the
      need to evaluate the epigenetic component in order to gain better knowledge of
      breast cancer biology, thereby, to improve patient management. Clearly, however,
      the epigenomic exploration of breast cancers has only just begun, recent studies
      having revealed the importance of DNA methylation in regions such as gene bodies
      and intergenic regions that still need to be explored.

PMID- 21946248
TI  - Expression of zona pellucida B proteins in juvenile rare minnow (Gobiocypris
      rarus) exposed to 17alpha-ethinylestradiol, 4-nonylphenol and bisphenol A.
AB  - Zona pellucida (ZP) containing proteins are glycoproteins in teleost chorion and
      are encoded by several gene subfamilies, mainly including ZPA, ZPB, ZPC and ZPX
      genes. In teleost species, ZP genes are expressed either in liver under
      regulation of estrogen or in ovary. In the present study, five ZP gene isoforms
      were isolated and characterized in Gobiocypris rarus. The putative amino acid
      sequences of these ZP gene isoforms contain the typical trefoil motif and a ZP
      domain. These five G. rarus ZP gene isoforms were named as grZPB.1, grZPB.2,
      grZPB.3, grZPB.4 and grZPB.5. Real-time quantitative reverse transcription PCR
      (RT-qPCR) analysis indicated that all these ZP mRNA isoforms were exclusively
      expressed in ovary. G. rarus juveniles at the age of 21 days postfertilization
      were exposed to 17alpha-ethinylestradiol (EE2; 0.01, 0.1 and 1 nM), 4-nonylphenol
      (4-NP; 10, 100 and 1000 nM) or bisphenol A (BPA; 0.1, 1 and 10nM) for 3 days.
      mRNA expressions of ZPB isoforms following the exposure to xenoestrogen were
      detected by RT-qPCR. Data were analyzed by the 2(-??Cq) method. The results
      indicate that induction by 0.1-1nM EE2 on mRNA expression of the grZPB isoforms
      is weaker than for vitellogenin. 4-NP exposures at three concentrations had
      differential effects on the grZPBs. BPA at three concentrations weakly induced
      mRNA expression of the grZPB isoforms.

PMID- 21946246
TI  - Current status of allogeneic transplantation for aggressive non-Hodgkin lymphoma.
AB  - PURPOSE OF REVIEW: To provide a succinct update on the role of allogeneic stem
      cell transplantation (allo-SCT) in the management of patients with aggressive
      lymphomas. To clarify the indications for allogeneic transplantation vis-a-vis
      autologous transplant and to discuss the rationale and potential benefits of
      reduced intensity conditioning (RIC), nonmyeloablative (NMA) transplant, T-cell
      depletion and variations in graft vs. host disease (GVHD) prophylaxis. RECENT
      FINDINGS: Considerable effort has been spent in developing transplant regimens
      with reduced toxicity and reduced GVHD. The role of allogeneic transplantation
      has also been redefined in light of advances in lymphoma classification,
      diagnostic methods, particularly PET scan and advances in transplant technology.
      Haplo and umbilical cord blood SCT allow identification of a donor for nearly all
      patients. SUMMARY: In diffuse large B-cell lymphoma, the outcome of allo-SCT
      depends on patient characteristics and chemosensitivity. It is useful after
      failure of auto-SCT and in partial responses to salvage therapy. Allo-SCT may be
      the treatment of choice for advanced T-cell and natural killer cell lymphoma and
      for adult T-cell leukemia-lymphoma. Prophylactic or preemptive donor lymphocyte
      infusion may be useful, but requires controlled studies. RIC and NMA conditioning
      have reduced early toxicity but are associated with increased risk for disease
      recurrence. Promising data have been reported from a novel conditioning regimen
      combining NMA with ibritumomab tiuxetan. T-cell depletion reduces chronic GVHD
      but has some increase in rate of recurrence. Rapamycin may be associated with
      reduction in risk for disease recurrence.

PMID- 21946250
TI  - Google walkability: a new tool for local planning and public health research?
AB  - BACKGROUND: We investigate the association of different composite walkability
      measures with individual walking behaviors to determine if multicomponent metrics
      of walkability are more useful for assessing the health impacts of the built
      environment than single component measures. METHODS: We use a previously
      published composite walkability measure as well as a new measure that was
      designed to represent easier methods of combination and which includes 2 metrics
      obtained using Google data sources. Logistic regression was used to assess the
      relationship between walking behavior and walkability metrics. RESULTS: Our
      results suggest that composite measures of walkability are more consistent
      predictors of walking behavior than single component measures. Furthermore, a
      walkability measure developed using free, publicly available data from Google was
      found to be nearly as effective in predicting walking outcomes as a walkability
      measure derived without such publicly and nationally available measures.
      CONCLUSIONS: Our findings demonstrate the effectiveness of free and locally
      relevant data for assessing walkable environments. This facilitates the use of
      locally derived and adaptive tools for evaluating the health impacts of the built
      environment.

PMID- 21946249
TI  - Persistent adult zebrafish behavioral deficits results from acute embryonic
      exposure to gold nanoparticles.
AB  - As the number of products containing nanomaterials increase, human exposure to
      nanoparticles (NPs) is unavoidable. Presently, few studies focus on the potential
      long-term consequences of developmental NP exposure. In this study, zebrafish
      embryos were acutely exposed to three gold NPs that possess functional groups
      with differing surface charge. Embryos were exposed to 50 MUg/mL of 1.5 nm gold
      nanoparticles (AuNPs) possessing negatively charged 2-mercaptoethanesulfonic acid
      (MES) or neutral 2-(2-(2-mercaptoethoxy)ethoxy)ethanol (MEEE) ligands or 10
      MUg/mL of the AuNPs possessing positively charged trimethylammoniumethanethiol
      (TMAT). Both MES- and TMAT-AuNP exposed embryos exhibited hypo-locomotor
      activity, while those exposed to MEEE-AuNPs did not. A subset of embryos that
      were exposed to 1.5 nm MES- and TMAT-AuNPs during development from 6 to 120 h
      post fertilization was raised to adulthood. Behavioral abnormalities and the
      number of survivors into adulthood were evaluated at 122 days post fertilization.
      We found that both treatments induced abnormal startle behavior following a tap
      stimulus. However, the MES-AuNPs exposed group also exhibited abnormal adult
      behavior in the light and had a lower survivorship into adulthood. This study
      demonstrates that acute, developmental exposure to 1.5 nm MES- and TMAT-AuNPs,
      two NPs differing only in the functional group, affects larval behavior, with
      behavioral effects persisting into adulthood.

PMID- 21946251
TI  - Pertussis-related hyperleukocytosis: role of hyperhydration and exchange
      transfusion.

PMID- 21946252
TI  - The hybrid hospitalist teaching service: an innovative model for individualized
      learning, patient case-mix, and medical student and resident education.
AB  - BACKGROUND: Alternative inpatient teams are increasing, but little is known about
      their impact on patient care and trainee education. PURPOSE: To evaluate whether
      a hybrid hospitalist teaching service meets trainee and attending educational,
      clinical, support, patient-mix, autonomy, and efficiency needs. METHODS: Post
      pediatric rotations, team members anonymously completed surveys with Likert-scale
      and open-ended questions. RESULTS: In total, 78 of 80 surveys were completed.
      Trainees rated educational, clinical, support, and case-mix domains highly.
      Senior residents responded positively for autonomy, education, and opinions of
      hospitalists, but neutrally on leadership. Attending scores varied for
      efficiency, teaching, and clinical duties; the service resulted in direct
      observation and teaching outside of rounds, but poor delineation of roles and
      expectations impeded clinical task completion, teaching on rounds, and attending
      meetings. CONCLUSIONS: This model is a satisfying, well-accepted means of
      enhancing trainee education and patient care, but roles and expectations must be
      clearly defined to maximize efficiency and satisfaction.

PMID- 21946253
TI  - Supporting children after single- incident trauma: parents' views.
AB  - OBJECTIVE: To strengthen trauma-informed health care by exploring parents'
      experiences of assisting their child after single-incident trauma (eg, violence,
      accidents, and sudden loss). METHOD: Semistructured interviews with parents (N =
      33) of 25 exposed children (8-12 years). RESULTS: Responsive parenting after
      trauma emerged as a core theme, consisting of (a) being aware of a child's needs
      and (b) acting on these needs. The authors identified 14 strategies, such as
      comparing behavior with siblings' behavior and providing opportunities to talk.
      Parents felt that their capacity to be responsive was influenced by their own
      level of distress. CONCLUSION: The authors propose a model of Relational PTSD
      (posttraumatic stress disorder) and Recovery to assist health care professionals
      working with children exposed to trauma. The results also point to the need to
      recognize the challenge that parents face when supporting a child after traumatic
      exposure and to align more with parents about procedures that may cause the child
      to be reminded of the event.

PMID- 21946254
TI  - A review of sexual health web sites for adolescents.
AB  - BACKGROUND: The popularity of the Internet for health information and the growing
      availability of online access make the Internet a compelling medium for health
      promotion and HIV/STI prevention efforts for adolescents. Many private and
      federally funded programs have incorporated Web-based approaches and online
      technologies into their sexual education and HIV/STI prevention efforts for
      adolescents. These efforts have resulted in numerous Web sites and varied online
      content. This content is currently understudied and underevaluated. In this
      study, current sexual health Web sites targeted at adolescents were catalogued
      and coded. METHODS: Web sites targeted at adolescents were coded for educational
      content, credibility, usability, as well as interactivity. RESULTS: A significant
      amount of sexual health information geared toward teens is available online. All
      the Web sites reviewed showed deficiencies in educational content, as well as
      deficiencies in usability, authority, and interactivity. Planned Parenthood's Web
      site was the most well rounded of the sites assessed.

PMID- 21946255
TI  - Roles of young serine-endopeptidase genes in survival and reproduction revealed
      rapid evolution of phenotypic effects at adult stages.
AB  - Our recent study found that 30% of young genes were essential for viability that
      determines development through stages from embryo to pupae in Drosophila
      melanogaster, revealing rapidly evolving genetic components involved in the
      evolution of development. Meanwhile, many young genes did not produce complete
      lethal phenotype upon constitutive knockdown, suggesting that they may not be
      essential for viability. These genes, nevertheless, were fixed by natural
      selection, and might play an important functional role in their adult stage. Here
      we present a detailed demonstration that a newly duplicated serine-type
      endopeptidase gene that originated in the common ancestor in the D. melanogaster
      subgroup 6~11 million years ago, named Slfc, revealing a strong effect in post
      eclosion. Although animals survived constitutive knockdown of Slfc to adult
      stage, however, their life span reduced significantly by two-thirds compared to
      wildtype. Furthermore, the Slfc-RNAi males dropped their fertility to less than
      10% of the wildtype level, with over 80% of these males being sterile. The Slfc
      RNAi females, on the other hand, showed a slight reduction in fertility. This
      case study demonstrates that a young gene can contribute to fitness on the three
      important traits of life history in adults, including the life expectancy, male
      fertility and female fertility, suggesting that new genes can quickly evolve and
      impact multiple phenotypes.

PMID- 21946256
TI  - Gene expression profiling of CD8+ T cells predicts prognosis in patients with
      Crohn disease and ulcerative colitis.
AB  - Crohn disease (CD) and ulcerative colitis (UC) are increasingly common, chronic
      forms of inflammatory bowel disease. The behavior of these diseases varies
      unpredictably among patients. Identification of reliable prognostic biomarkers
      would enable treatment to be personalized so that patients destined to experience
      aggressive disease could receive appropriately potent therapies from diagnosis,
      while those who will experience more indolent disease are not exposed to the
      risks and side effects of unnecessary immunosuppression. Using transcriptional
      profiling of circulating T cells isolated from patients with CD and UC, we
      identified analogous CD8+ T cell transcriptional signatures that divided patients
      into 2 otherwise indistinguishable subgroups. In both UC and CD, patients in
      these subgroups subsequently experienced very different disease courses. A
      substantially higher incidence of frequently relapsing disease was experienced by
      those patients in the subgroup defined by elevated expression of genes involved
      in antigen-dependent T cell responses, including signaling initiated by both IL-7
      and TCR ligation - pathways previously associated with prognosis in unrelated
      autoimmune diseases. No equivalent correlation was observed with CD4+ T cell gene
      expression. This suggests that the course of otherwise distinct autoimmune and
      inflammatory conditions may be influenced by common pathways and identifies what
      we believe to be the first biomarker that can predict prognosis in both UC and CD
      from diagnosis, a major step toward personalized therapy.

PMID- 21946258
TI  - Phospholipase A(2)-susceptible liposomes of anticancer double lipid-prodrugs.
AB  - A novel approach to anticancer drug delivery is presented based on lipid-like
      liposome-forming anticancer prodrugs that are susceptible to secretory
      phospholipase A(2) (sPLA(2)) that is overexpressed in several cancer types. The
      approach provides a selective unloading of anticancer drugs at the target
      tissues, as well as circumvents the necessity for "conventional" drug loading. In
      our attempts to improve the performance of the liposomes in vivo, several
      PEGylated and non-PEGylated liposomal formulations composed of a retinoid prodrug
      premixed with the sPLA(2)-hydrolyzable DPPC (1,2-dipalmitoyl-sn-glycero-3
      phosphocholine) were prepared. Besides favorably modifying the physicochemical
      properties of the liposomes, the incorporation of DPPC and PEG-lipids in the
      liposomes should substantially enhance the enzymatic activity, as concluded from
      literature. In addition, one can reap benefits from the presumed permeability
      enhancing effect of the liberated fatty acids and lysolipids. The size
      distribution of the prepared liposomes as well as their phase behavior, enzymatic
      hydrolysis, and cytotoxicity, in the presence and absence of sPLA(2), were
      determined. The liposomes were around 100nm in diameter and in the gel/fluid
      coexistence region at 37 degrees C. The enzymatic hydrolysis of the prodrug was
      pronouncedly accelerated upon the premixing with DPPC, and the hydrolysis was
      further enhanced by PEGylation. Interestingly, the faster hydrolysis of the
      prodrug and the released fatty acids and lysolipids from DPPC did not improve the
      cytotoxicity of the mixture; the effect of combining the prodrug with DPPC was
      additive and not synergistic. The data presented here question the significance
      of the permeability enhancing effects claimed for fatty acids and lysolipids at
      the target cell membrane, and whether these effects can be achieved using
      physiologically achievable concentrations of fatty acids and lysolipids.

PMID- 21946259
TI  - Harmonization of regulatory approaches for evaluating therapeutic equivalence and
      interchangeability of multisource drug products: workshop summary report.
AB  - Regulatory approaches for evaluating therapeutic equivalence of multisource (or
      generic) drug products vary among different countries and/or regions.
      Harmonization of these approaches may decrease the number of in vivo
      bioequivalence studies and avoid unnecessary drug exposure to humans. Global
      harmonization for regulatory requirements may be promoted by a better
      understanding of factors underlying product performance and expectations from
      different regulatory authorities. This workshop provided an opportunity for
      pharmaceutical scientists from academia, industry and regulatory agencies to have
      open discussions on current regulatory issues and industry practices,
      facilitating harmonization of regulatory approaches for establishing therapeutic
      equivalence and interchangeability of multisource drug products.

PMID- 21946257
TI  - Detection of human cytomegalovirus in medulloblastomas reveals a potential
      therapeutic target.
AB  - Medulloblastomas are the most common malignant brain tumors in children. They
      express high levels of COX-2 and produce PGE2, which stimulates tumor cell
      proliferation. Human cytomegalovirus (HCMV) is prevalent in the human population
      and encodes proteins that provide immune evasion strategies and promote oncogenic
      transformation and oncomodulation. In particular, HCMV induces COX-2 expression;
      STAT3 phosphorylation; production of PGE2, vascular endothelial growth factor,
      and IL-6; and tumor formation in vivo. Here, we show that a large proportion of
      primary medulloblastomas and medulloblastoma cell lines are infected with HCMV
      and that COX-2 expression, along with PGE2 levels, in tumors is directly
      modulated by the virus. Our analysis indicated that both HCMV immediate-early
      proteins and late proteins are expressed in the majority of primary
      medulloblastomas. Remarkably, all of the human medulloblastoma cell lines that we
      analyzed contained HCMV DNA and RNA and expressed HCMV proteins at various levels
      in vitro. When engrafted into immunocompromised mice, human medulloblastoma cells
      induced expression of HCMV proteins. HCMV and COX-2 expression correlated in
      primary tumors, cell lines, and medulloblastoma xenografts. The antiviral drug
      valganciclovir and the specific COX-2 inhibitor celecoxib prevented HCMV
      replication in vitro and inhibited PGE2 production and reduced medulloblastoma
      tumor cell growth both in vitro and in vivo. Ganciclovir did not affect the
      growth of HCMV-negative tumor cell lines. These findings imply an important role
      for HCMV in medulloblastoma and suggest HCMV as a novel therapeutic target for
      this tumor.

PMID- 21946260
TI  - Formulation and evaluation of an in situ gel forming system for controlled
      delivery of triptorelin acetate.
AB  - The novel physical hydrogels composed of chitosan or its water soluble
      derivatives such as carboxymethyl chitosan (CMCh) and sodium carboxymethyl
      chitosan (NaCMCh) and opened ring polyvinyl pyrrolidone (OP-PVP) were used as a
      controlled delivery system for triptorelin acetate, a luteinizing-releasing
      hormone agonist. The in situ gel forming system designed according to physical
      interactions such as chains entanglements and hydrophilic attractions especially
      h-bonds of chitosan and/or NaCMCh and OR-PVP. In order to increase in situ gel
      forming rate the chitosan microspheres prepared through spray drying technique.
      The chitosan or NaCMCh/OR-PVP blends prepared at different ratios (0.05, 0.10,
      0.12, 0.16, 0.20 and 0.24) and suspended in sesame oil as non-aqueous vehicle at
      different solid content (10-30%). The suitable ratio of polymers with faster in
      situ gel forming rate was selected for in vivo studies. The gel formation and
      drug release from the system was evaluated both in vitro and in vivo. In vitro
      and in vivo results were compared with Diphereline SR 3.75mg, a commercially
      available controlled delivery system of triptorelin. In vitro release studies
      showed a sustained release profile for about 192h with first order kinetics. In
      vivo studies on male rats by determination of serum testosterone were confirmed
      the acceptable performance of in situ gel forming system compared with
      Diphereline SR in decreasing the serum testosterone level for 35days,
      demonstrating the potential of the novel in situ gel forming system for
      controlled delivery of peptides.

PMID- 21946261
TI  - Kinetic efficiency: the missing metric for enhancing compound quality?
AB  - The kinetics of ligand-target interactions have been recognised as being
      instrumental in dictating the efficacy of drug action. Increased focus on kinetic
      signatures in drug discovery has concincided with improvements in label free
      methodology for measuring kinetic parameters. Simultaneously, focus has also been
      applied to increasing the quality of compounds, in terms of their physicochemical
      properties. To facilitate this drive towards higher compound quality, metrics
      such as ligand efficiency and enthalpic efficiency have been employed. We propose
      another metric, kinetic efficiency, that may be used pragmatically to help
      identify those compounds displaying differentiated kinetic behaviour. The
      combination of these metrics has the potential to improve decision-making in drug
      discovery leading to higher quality compounds and series.

PMID- 21946262
TI  - Recognizing, responding to and reporting patient deterioration: transferring
      simulation learning to patient care settings.
AB  - BACKGROUND: A simulation program was implemented in a pre-registration nursing
      curriculum for developing nursing students' performances in assessing, managing
      and reporting in relation to patients with physiological deterioration. AIM: To
      explore nursing students' experiences of how a simulation programme has prepared
      them to transfer their performance to clinical practice, in their encounters with
      deteriorating patients in ward. METHOD: A qualitative study using a critical
      incident technique was conducted. After they had undertaken a simulation program,
      fifteen undergraduate nursing students, who had encountered deteriorating
      patients in their clinical practicum in wards were interviewed using semi
      structured questionnaires. Content analysis was used to analyse the data.
      RESULTS: Four main themes emerged describing key factors influencing the transfer
      of simulation learning to clinical practice; memory, involving simulation
      learning enhanced storage and retrieval of knowledge; mnemonics as transfer tools
      for performing systematic physical assessment and reporting a patient's
      deterioration to a doctor; recognizing similar situations, where students used
      experiences from similar simulation situation to identify problems and initiate
      nursing interventions for their patients; and finally, emotional responses, that
      have both negative and positive impacts on transferring their simulation
      learning. Two other main themes emerged regarding strategies to facilitate
      transfer; self-directed learning for promoting the retention of simulation
      learning; and, realism, where simulated patients could be used to provide real
      life clinical experiences. CONCLUSION: The findings provide an understanding of
      how a simulation program may impact on the nursing students' performances in
      clinical practice, which is useful information for future improvement of
      programmes to optimize learning and transfer effective care to patient care
      settings.

PMID- 21946263
TI  - Characteristics of parents receiving counseling from child's doctor to limit
      child's sugar drink consumption.
AB  - BACKGROUND: Due to limited information on sugar drink counseling, characteristics
      of parents who reported ever receiving counseling from a child's doctor to limit
      a child's sugar drink intake were examined. METHODS: This cross-sectional
      analysis was conducted on a convenient sample of 1570 US parents (aged >= 18
      years) using the 2009 HealthStyles Survey. The outcome measure was parents with
      children aged <= 18 years who reported being told by a child's doctor to limit a
      child's sugar drink intake. Data were weighted to provide national estimates.
      Multivariable logistic regression was used to examine factors associated with
      ever receiving sugar-drink counseling from a child's doctor. RESULTS: Only 23% of
      parents reported receiving counseling from a child's doctor to limit a child's
      sugar drink intake. Parental factors significantly associated with receiving this
      counseling were: being male (adjusted odds ratio (OR) = 1.38; 95% confidence
      interval (CI) = 1.02, 1.86), having an annual household income of <$25 000
      (versus >=$60 000, OR = 2.12; 95% CI = 1.33, 3.38) and parents who agreed with
      'enjoying learning about health issues' (versus disagree, OR = 2.43; 95% CI =
      1.36, 4.36). Age, race/ethnicity, education and marital status were not
      significantly associated with receiving counseling. CONCLUSIONS: Few parents
      reported ever receiving counseling from a child's doctor, and we found a few
      differences among those reporting sugar drink counseling.

PMID- 21946265
TI  - Stress precipitates functional deficits following striatal silent stroke: a
      synergistic effect.
AB  - Stress has been linked to structural and functional outcomes after stroke.
      Moreover, the striatum, both dorsal and ventral, is a vital regulator of stress
      perception and associated physiological responses. This study investigates
      potential synergistic effects of focal stroke in the ventrolateral striatum and
      restraint stress on motor and spatial performance. Adult male Long-Evans rats
      were pre-trained in a skilled reaching task and randomly assigned to sham, stroke
      only, stress-only and stroke+stress conditions. Ventrolateral striatal focal
      ischemia was induced by endothelin-1 (ET-1) infusion. Rats in stress-only and
      stroke+stress groups received 21 days of mild restraint stress after stroke. All
      rats were tested in the skilled reaching task and the ziggurat task (ZT) for post
      stroke motor and spatial performance. There was no effect of ventrolateral
      striatal ischemia or stress alone on motor and spatial performance. Notably,
      stroke and stress interacted synergistically to reduce reaching success and to
      disrupt qualitative aspects of movement performance in the absence of
      histological differences in lesion size. Thus, stress can precipitate behavioural
      deficits after focal ischemia even in the absence of significant functional
      deficits on its own. These results emphasize the importance of prevention
      programmes to control post-stroke levels of stress in clinical populations.

PMID- 21946266
TI  - Higher free D-aspartate and N-methyl-D-aspartate levels prevent striatal
      depotentiation and anticipate L-DOPA-induced dyskinesia.
AB  - In Parkinson's disease (PD) progressive alteration of striatal N-methyl-D
      aspartate receptors (NMDARs) signaling has emerged as a considerable factor for
      the onset of the adverse motor effects of long-term levodopa (l-DOPA) treatment.
      In this regard, the NMDAR channel blocker amantadine is so far the only drug
      available for clinical use that attenuates L-DOPA-induced dyskinesia (LID). In
      this study, we examined the influence of a basal corticostriatal hyper
      glutamatergic transmission in the appearance of dyskinesia, using a genetic mouse
      model lacking D-Aspartate Oxidase (DDO) enzyme (Ddo(-/-) mice). We found that, in
      Ddo(-/-) mice, non-physiological, high levels of the endogenous free D-amino
      acids D-aspartate (D-Asp) and NMDA, known to stimulate NMDAR transmission,
      resulted in the loss of corticostriatal synaptic depotentiation and precocious
      expression of LID. Interestingly, the block of depotentiation precedes any change
      in dopaminergic transmission associated to 6-OHDA lesion and l-DOPA treatment.
      Indeed, lesioned mutant mice display physiological L-DOPA-dependent enhancement
      of striatal D1 receptor/PKA/protein phosphatase-1 and ERK signaling. Moreover, in
      line with synaptic rearrangements of NMDAR subunits occurring in dyskinetic
      animal models, a short L-DOPA treatment produces a dramatic and selective
      reduction of the NR2B subunit in the striatal post-synaptic fraction of Ddo(-/-)
      lesioned mutants but not in controls. These data indicate that a preexisting
      hyper-glutamatergic tone at NMDARs in Ddo(-/-) mice produce abnormal striatal
      synaptic changes that, in turn, facilitate the onset of LID.

PMID- 21946267
TI  - A re-assessment of the effects of intracortical delivery of inosine on
      transmidline growth of corticospinal tract axons after unilateral lesions of the
      medullary pyramid.
AB  - This study was undertaken as part of the NIH "Facilities of Research Excellence
      Spinal Cord Injury", which supports independent replication of published studies.
      Here, we repeat an experiment reporting that intracortical delivery of inosine
      promoted trans-midline growth of corticospinal tract (CST) axons in the spinal
      cord after unilateral injury to the medullary pyramid. Rats received unilateral
      transections of the medullary pyramid and 1 day later, a cannula assembly was
      implanted into the sensorimotor cortex contralateral to the pyramidotomy to
      deliver either inosine or vehicle. The cannula assembly was attached to an
      osmotic minipump that was implanted sub-cutaneously. Seventeen or 18 days post
      injury, the CST was traced by making multiple injections of miniruby-BDA into the
      sensorimotor cortex. Rats were killed for tract tracing 14 days after the BDA
      injections. Sections through the cervical spinal cord were stained for BDA and
      immunostained for GAP43 and GFAP. Our results revealed no evidence for enhanced
      growth of CST axons across the midline of the dorsal column in rats that received
      intracortical infusion of inosine. Possible reasons for the failure to replicate
      are discussed.

PMID- 21946268
TI  - Microglial signalling mechanisms: Cathepsin S and Fractalkine.
AB  - A recent major conceptual advance has been the recognition of the importance of
      immune system-neuron interactions in the modulation of spinal pain processing. In
      particular, pro-inflammatory mediators secreted by immune competent cells such as
      microglia modulate nociceptive function in the injured CNS and following
      peripheral nerve damage. Chemokines play a pivotal role in mediating neuronal
      microglial communication which leads to increased nociception. Here we examine
      the evidence that one such microglial mediator, the lysosomal cysteine protease
      Cathepsin S (CatS), is critical for the maintenance of neuropathic pain via
      cleavage of the transmembrane chemokine Fractalkine (FKN). Both CatS and FKN
      mediate critical physiological functions necessary for immune regulation. As key
      mediators of homeostatic functions it is not surprising that imbalance in these
      immune processes has been implicated in autoimmune disorders including Multiple
      Sclerosis and Rheumatoid Arthritis, both of which are associated with chronic
      pain. Thus, impairment of the CatS/FKN signalling pair constitutes a novel
      therapeutic approach for the treatment of chronic pain.

PMID- 21946270
TI  - Extent of pre-operative L-DOPA-induced dyskinesia predicts the severity of graft
      induced dyskinesia after fetal dopamine cell transplantation.
AB  - Graft-induced dyskinesia has emerged as a problematic side effect after
      transplantation of fetal dopamine cells into the striatum of patients with
      Parkinson's disease. These adverse effects of dystonic and choreatiform
      hyperkinesias that persisted even after withdrawal of L-DOPA medication are not
      yet fully understood, which poses a main obstacle for the re-initiation of neural
      transplantation in Parkinson's disease. The severity of pre-operative L-DOPA
      induced dyskinesia has been proposed as one of several parameters influencing the
      development of graft-induced dyskinesia. We have therefore characterized graft
      induced dyskinesia in the rat model of Parkinson's disease in animals with either
      mild or severe pre-operative L-DOPA-induced dyskinesia. We show that animals with
      intrastriatal grafts of fetal dopamine cells and severe pre-operative L-DOPA
      induced dyskinesia will reduce their L-DOPA-induced dyskinesia scores by more
      than 75% but at the same time develop graft-induced dyskinesia of intermediate to
      strong severity. In contrast, animals with dopamine grafts of similar size but
      only mild pre-operative L-DOPA-induced dyskinesia also developed graft-induced
      dyskinesia but this was very mild and of intermediate severity only in a single
      animal. Severity of pre-operative L-DOPA-induced dyskinesia was correlated with
      the severity of graft-induced dyskinesia. Our data suggest that patients with no
      or only mild L-DOPA-induced dyskinesia may carry a lower risk for the development
      of graft-induced dyskinesia and therefore are better candidates to receive
      intracerebral grafts of fetal dopamine cells as compared to patients with more
      pronounced L-DOPA-induced dyskinesia.

PMID- 21946269
TI  - A mouse model of blast-induced mild traumatic brain injury.
AB  - Improvised explosive devices (IEDs) are one of the main causes for casualties
      among civilians and military personnel in the present war against terror. Mild
      traumatic brain injury from IEDs induces various degrees of cognitive, emotional
      and behavioral disturbances but knowledge of the exact brain pathophysiology
      following exposure to blast is poorly understood. The study was aimed at
      establishing a murine model for a mild BI-TBI that isolates low-level blast
      pressure effects to the brain without systemic injuries. An open-field explosives
      detonation was used to replicate, as closely as possible, low-level blast trauma
      in the battlefield or at a terror-attack site. No alterations in basic
      neurological assessment or brain gross pathology were found acutely in the blast
      exposed mice. At 7 days post blast, cognitive and behavioral tests revealed
      significantly decreased performance at both 4 and 7 m distance from the blast
      (5.5 and 2.5 PSI, respectively). At 30 days post-blast, clear differences were
      found in animals at both distances in the object recognition test, and in the 7 m
      group in the Y maze test. Using MRI, T1 weighted images showed an increased BBB
      permeability 1 month post-blast. DTI analysis showed an increase in fractional
      anisotropy (FA) and a decrease in radial diffusivity. These changes correlated
      with sites of up-regulation of manganese superoxide dismutase 2 in neurons and
      CXC-motif chemokine receptor 3 around blood vessels in fiber tracts. These
      results may represent brain axonal and myelin abnormalities. Cellular and
      biochemical studies are underway in order to further correlate the blast-induced
      cognitive and behavioral changes and to identify possible underlying mechanisms
      that may help develop treatment- and neuroprotective modalities.

PMID- 21946272
TI  - Training and anti-CSPG combination therapy for spinal cord injury.
AB  - Combining different therapies is a promising strategy to promote spinal cord
      repair, by targeting axon plasticity and functional circuit reconnectivity. In
      particular, digestion of chondroitin sulphate proteoglycans at the site of the
      injury by the activity of the bacterial enzyme chondrotinase ABC, together with
      the development of intensive task specific motor rehabilitation has shown
      synergistic effects to promote behavioural recovery. This review describes the
      mechanisms by which chondroitinase ABC and motor rehabilitation promote neural
      plasticity and we discuss their additive and independent effects on promoting
      behavioural recovery.

PMID- 21946271
TI  - Purinergic systems, neuropathic pain and the role of microglia.
AB  - We have learned various data on the role of purinoceptors (P2X4, P2X7, P2Y6 and
      P2Y12) expressed in spinal microglia and several factors that presumably activate
      microglia in neuropathic pain after peripheral nerve injury. Purinergic receptor
      mediated spinal microglial functions make a critical contribution to
      pathologically enhanced pain processing in the dorsal horn. Microglial
      purinoceptors might be promising targets for treating neuropathic pain. A
      predicted therapeutic benefit of interfering with microglial purinergic receptors
      may be that normal pain sensitivity would be unaffected since expression or
      activity of most of these receptors are upregulated or enhanced predominantly in
      activated microglia in the spinal cord where damaged sensory fibers project.

PMID- 21946273
TI  - Prehospital assessment and management of chest pain needs improving.

PMID- 21946274
TI  - A chemical-genetic screen reveals a mechanism of resistance to PI3K inhibitors in
      cancer.
AB  - Linking the molecular aberrations of cancer to drug responses could guide
      treatment choice and identify new therapeutic applications. However, there has
      been no systematic approach for analyzing gene-drug interactions in human cells.
      Here we establish a multiplexed assay to study the cellular fitness of a panel of
      engineered isogenic cancer cells in response to a collection of drugs, enabling
      the systematic analysis of thousands of gene-drug interactions. Applying this
      approach to breast cancer revealed various synthetic-lethal interactions and drug
      resistance mechanisms, some of which were known, thereby validating the method.
      NOTCH pathway activation, which occurs frequently in breast cancer, unexpectedly
      conferred resistance to phosphoinositide 3-kinase (PI3K) inhibitors, which are
      currently undergoing clinical trials in breast cancer patients. NOTCH1 and
      downstream induction of c-MYC over-rode the dependency of cells on the PI3K-mTOR
      pathway for proliferation. These data reveal a new mechanism of resistance to
      PI3K inhibitors with direct clinical implications.

PMID- 21946275
TI  - Chemical inhibitors of monogalactosyldiacylglycerol synthases in Arabidopsis
      thaliana.
AB  - Monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG) are the
      main lipids in photosynthetic membranes in plant cells. They are synthesized in
      the envelope surrounding plastids by MGD and DGD galactosyltransferases. These
      galactolipids are critical for the biogenesis of photosynthetic membranes, and
      they act as a source of polyunsaturated fatty acids for the whole cell and as
      phospholipid surrogates in phosphate shortage. Based on a high-throughput
      chemical screen, we have characterized a new compound, galvestine-1, that
      inhibits MGDs in vitro by competing with diacylglycerol binding. Consistent
      effects of galvestine-1 on Arabidopsis thaliana include root uptake, circulation
      in the xylem and mesophyll, inhibition of MGDs in vivo causing a reduction of
      MGDG content and impairment of chloroplast development. The effects on pollen
      germination shed light on the contribution of galactolipids to pollen-tube
      elongation. The whole-genome transcriptional response of Arabidopsis points to
      the potential benefits of galvestine-1 as a unique tool to study lipid
      homeostasis in plants.

PMID- 21946276
TI  - On-resin N-methylation of cyclic peptides for discovery of orally bioavailable
      scaffolds.
AB  - Backbone N-methylation is common among peptide natural products and has a
      substantial impact on both the physical properties and the conformational states
      of cyclic peptides. However, the specific impact of N-methylation on passive
      membrane diffusion in cyclic peptides has not been investigated systematically.
      Here we report a method for the selective, on-resin N-methylation of cyclic
      peptides to generate compounds with drug-like membrane permeability and oral
      bioavailability. The selectivity and degree of N-methylation of the cyclic
      peptide was dependent on backbone stereochemistry, suggesting that conformation
      dictates the regiochemistry of the N-methylation reaction. The permeabilities of
      the N-methyl variants were corroborated by computational studies on a 1,024
      member virtual library of N-methyl cyclic peptides. One of the most permeable
      compounds, a cyclic hexapeptide (molecular mass = 755 Da) with three N-methyl
      groups, showed an oral bioavailability of 28% in rat.

PMID- 21946278
TI  - Protection against Acinetobacter baumannii infection via its functional
      deprivation of biofilm associated protein (Bap).
AB  - Acinetobacter baumannii, a major nosocomial pathogen, has remarkable capacity to
      acquire antimicrobial resistance attributable to its biofilm formation ability.
      Biofilm associated protein (Bap), a specific cell surface protein, is directly
      involved in biofilm formation by A. baumannii and plays a major role in bacterial
      infectious processes. In the present study we cloned, expressed and purified a
      371 amino acid subunit of Bap. Mice were immunized using recombinant Bap subunit.
      They were then challenged with A. baumannii to evaluate the immunogenicity and
      protectivity of Bap subunit. Humoral immune response to Bap was determined by
      ELISA. Injection of Bap subunit resulted in high antibody titers. Decrease in
      bacterial cell counts of the immunized mice was evident 18 h after challenge.
      Reaction of antibodies against Bap with several strains suggests that not only
      immunodominant regions of Bap in A. baumannii strains are conserved but also have
      the same epitope presenting pattern in different strains. Immunodominant region
      of Bap possesses target sites for a protective humoral immune response to A.
      baumannii. This seems to be a conserved region erecting efficacy of Bap as an
      appropriate vaccine candidate.

PMID- 21946277
TI  - Affinity-based proteomics reveal cancer-specific networks coordinated by Hsp90.
AB  - Most cancers are characterized by multiple molecular alterations, but
      identification of the key proteins involved in these signaling pathways is
      currently beyond reach. We show that the inhibitor PU-H71 preferentially targets
      tumor-enriched Hsp90 complexes and affinity captures Hsp90-dependent oncogenic
      client proteins. We have used PU-H71 affinity capture to design a proteomic
      approach that, when combined with bioinformatic pathway analysis, identifies
      dysregulated signaling networks and key oncoproteins in chronic myeloid leukemia.
      The identified interactome overlaps with the well-characterized altered proteome
      in this cancer, indicating that this method can provide global insights into the
      biology of individual tumors, including primary patient specimens. In addition,
      we show that this approach can be used to identify previously uncharacterized
      oncoproteins and mechanisms, potentially leading to new targeted therapies. We
      further show that the abundance of the PU-H71-enriched Hsp90 species, which is
      not dictated by Hsp90 expression alone, is predictive of the cell's sensitivity
      to Hsp90 inhibition.

PMID- 21946279
TI  - In vitro gliadin challenge: diagnostic accuracy and utility for the difficult
      diagnosis of celiac disease.
AB  - OBJECTIVES: Diagnosis of celiac disease is difficult when treatment with gluten
      free diet (GFD) is started before diagnosis and/or when the results of tests are
      inconsistent. The objective of this study was to evaluate the in vitro gliadin
      challenge. METHODS: The study cohort included patients without celiac disease
      (negative controls, n=57), patients with celiac disease (positive controls, n=166
      untreated and n=55 on GFD), and patients with difficult diagnosis (n=59). All
      patients underwent endoscopy for collection of duodenal samples, which served for
      the diagnosis of celiac disease and for the in vitro evaluation of the gliadin
      induced mucosal expression of seven inflammatory markers: PY99, ICAM-1
      (intercellular cell adhesion molecule), HLA-DR, CD3, CD25, CD69, and
      transglutaminase 2 IgA. Diagnostic work-up for celiac disease included the search
      of specific serum antibodies. Patients of the difficult diagnosis group were
      asked to stop GFD for repeated search of these antibodies under untreated
      conditions. The area under the receptor-operated curve (ROC) was used for
      statistical analyses on accuracy. RESULTS: HLA-DR had the highest accuracy for
      celiac disease diagnosis in analyses on negative controls and positive controls
      also excluding patients on GFD (area under ROC=0.99). Accuracy of test did not
      increase combining data of HLA-DR with data of other markers. Findings were
      similar in the 39 patients of the difficult diagnosis group undergoing the search
      celiac disease-specific antibodies under untreated conditions. CONCLUSIONS: The
      in vitro response of mucosal HLA-DR to gliadin is an accurate tool for the
      diagnosis of celiac disease also in patients with difficult diagnosis.

PMID- 21946280
TI  - Incidence, prevalence, and survival of chronic pancreatitis: a population-based
      study.
AB  - OBJECTIVES: Population-based data on chronic pancreatitis (CP) in the United
      States are scarce. We determined incidence, prevalence, and survival of CP in
      Olmsted County, MN. METHODS: Using Mayo Clinic Rochester's Medical Diagnostic
      Index followed by a detailed chart review, we identified 106 incident CP cases
      from 1977 to 2006 (89 clinical cases, 17 diagnosed only at autopsy); CP was
      defined by previously published Mayo Clinic criteria. We calculated age- and sex
      adjusted incidence (for each decade) and prevalence rate (1 January 2006) per
      100,000 population (adjusted to 2000 US White population). We compared the
      observed survival rate for patients with expected survival for age- and sex
      matched Minnesota White population. RESULTS: Median age at diagnosis of CP was 58
      years, 56% were male, and 51% had alcoholic CP. The overall (clinical cases or
      diagnosed only at autopsy) age- and sex-adjusted incidence was 4.05/100,000
      person-years (95% confidence interval (CI) 3.27-4.83). The incidence rate for
      clinical cases increased significantly from 2.94/100,000 during 1977-1986 to
      4.35/100,000 person-years during 1997-2006 (P<0.05) because of an increase in the
      incidence of alcoholic CP. There were 51 prevalent CP cases on 1 January 2006
      (57% male, 53% alcoholic). The age- and sex-adjusted prevalence rate per 100,000
      population was 41.76 (95% CI 30.21-53.32). At last follow-up, 50 patients were
      alive. Survival among CP patients was significantly lower than age- and sex
      specific expected survival in Minnesota White population (P<0.001). CONCLUSIONS:
      Incidence and prevalence of CP are low, and ~50% are alcohol related. The
      incidence of CP cases diagnosed during life is increasing. Survival of CP
      patients is lower than in the Minnesota White population.

PMID- 21946281
TI  - Long-term outcome of patients treated with double balloon enteroscopy for small
      bowel vascular lesions.
AB  - OBJECTIVES: Early rebleeding rate after endoscopic therapy with double balloon
      enteroscopy (DBE) of hemorrhagic small bowel vascular lesions (SBVL) varies
      between 10 and 50%. In recent reports, long-term follow-up of patients have been
      described but rebleeding risk factors are still not well established. The aim of
      the current study was to identify long-term treatment success rate and rebleeding
      risk factors after DBE therapy in a large cohort. METHODS: We conducted a single
      center, retrospective cohort study in a large French tertiary-referral center
      between January 2004 and December 2007. RESULTS: Among 261 patients presenting
      with obscure gastrointestinal bleeding (OGIB), SBVL was present in 133 patients
      and was treated successfully in 129 (97%) using mainly argon plasma coagulation.
      Ninety-eight patients were followed up for a mean period of 22.6+/-13.9 months
      (range 1-52). Rebleeding rate was 46% (45/98 patients) at 36 months. On
      multivariate analysis, the total number of observed lesions (hazard ratio (HR):
      1.15, 95% confidence interval (CI): 1.06-1.25, P=0.001) and the presence of a
      valvular and/or arrhythmic cardiac disease (HR: 2.50, 95% CI: 1.29-4.87, P=0.007)
      were significantly associated with the risk of rebleeding. Complication rate of
      therapeutic DBE was 2.3% with no mortality. CONCLUSIONS: Endoscopic therapy using
      DBE for SBVL in patients with recurrent OGIB allows a long-term remission in more
      than half of the patients. Independent rebleeding risk factors after a first
      endoscopic therapy are an increased number of SBVL and an associated
      valvular/arrhythmic heart disease.

PMID- 21946282
TI  - Clinicopathologic features of intraductal papillary neoplasm of the bile duct
      according to histologic subtype.
AB  - OBJECTIVES: Despite an increase in the reports of intraductal papillary neoplasm
      of the bile duct (IPN-B), the clinical characteristics and long-term prognosis of
      this disease are not well known compared with those of intraductal papillary
      mucinous neoplasms of the pancreas. The objective of our study was to compare the
      clinical features, radiologic findings, and clinical outcomes of IPN-B according
      to histologic subtype. METHODS: A retrospective analysis was performed on the
      medical records of 97 patients diagnosed with IPN-B by pathologic analysis of
      their surgical specimens between May 1995 and May 2010. We compared the clinical
      manifestations, radiological findings, pathologic grade, curative resection rate,
      recurrence, and overall survival according to four histologic subtypes: gastric
      (n=15), intestinal (n=46), pancreaticobiliary (n=33), and oncocytic (n=3), which
      were classified on the basis of hematoxylin and eosin staining and the
      immunohistochemical profile of mucin core proteins. RESULTS: Mucin hypersecretion
      was significantly more frequent in patients with gastric and intestinal types
      than it was in those with oncocytic and pancreaticobiliary types (P=0.014). There
      were no significant differences between groups regarding the presence of bile
      duct stones or tumor location. The frequency of invasive carcinoma in the
      pancreaticobiliary type was significantly higher than those in the gastric and
      intestinal types (72.7 vs. 26.7 and 32.6%, P<0.001 and P<0.001). When comparing
      the survival curves according to histologic subtype, patients with
      pancreaticobiliary type demonstrated significantly worse survival compared to
      those with gastric and intestinal types (P=0.035). CONCLUSIONS: Gastric and
      intestinal types of IPN-B have similar clinical characteristics compared with the
      pancreaticobiliary type, which has a worse prognosis.

PMID- 21946283
TI  - Novel probe-based confocal laser endomicroscopy criteria and interobserver
      agreement for the detection of dysplasia in Barrett's esophagus.
AB  - OBJECTIVES: Probe-based confocal laser endomicroscopy (pCLE) is an imaging
      technique that allows real-time in vivo histological assessment of Barrett's
      esophagus (BE). The objectives of this study were to create and test novel pCLE
      criteria for dysplastic BE (phase I), and to evaluate accuracy, interobserver
      variability, and learning curve in dysplasia prediction (phase II) using these
      criteria. METHODS: In phase I, using 50 pCLE videos, a pCLE expert and
      gastrointestinal pathologist formulated new BE criteria by consensus. These
      criteria were tested and refined in an independent set of 30 pCLE videos. In
      phase II, a formal training session for all assessors (three each
      experts/trainees) was conducted. Finally, using 75 testing videos, each video was
      interpreted as dysplasia (high-grade dysplasia (HGD)/cancer) vs. no dysplasia and
      the assessors' confidence in interpretation was noted. Interobserver agreement
      and accuracy (95% confidence interval (CI)) were determined for BE histology
      prediction. RESULTS: Of multiple pCLE criteria tested (phase I), only those with
      >=70% sensitivity or specificity were included in the final set: epithelial
      surface: saw-toothed; cells: enlarged; cells: pleomorphic; glands: not
      equidistant; glands: unequal in size and shape; goblet cells: not easily
      identified. Overall accuracy in diagnosing dysplasia was 81.5% (95% CI: 77.5-81),
      with no difference between experts vs. non-experts. Accuracy of prediction was
      significantly higher when endoscopists were "confident" about their diagnosis
      (98% (95-99) vs. 62% (54-70), P<0.001). Accuracy of dysplasia prediction for the
      first 30 videos was not different from the last 45 (93 vs. 81%, P=0.51). Overall
      agreement of the criteria was substantial, kappa=0.61 (0.53-0.69), with no
      difference between experts and non-experts. CONCLUSIONS: We demonstrate the
      development and validation of new pCLE criteria for the prediction of HGD/cancer
      in BE patients. Using these criteria, this study demonstrated that overall
      accuracy in predicting dysplasia was high with substantial interobserver
      agreement. After a structured teaching session, accuracy and agreement between
      experienced and non-experienced observers was not different, suggesting a short
      learning curve.

PMID- 21946284
TI  - Erosive esophagitis is a risk factor for Barrett's esophagus: a community-based
      endoscopic follow-up study.
AB  - OBJECTIVES: Symptomatic gastroesophageal reflux disease (GERD) is associated with
      a significantly increased risk of esophageal adenocarcinoma, but its natural
      history in the general population is poorly understood. Whether nonerosive reflux
      disease (NERD) is a risk factor for Barrett's esophagus (BE), the precursor of
      esophageal adenocarcinoma, is unknown. Furthermore, quantifying the risk of
      incident BE in those with untreated reflux esophagitis has not been possible. We
      aimed, in a prospective follow-up study with endoscopy, to evaluate the risk of
      BE in a cohort from the Swedish general population (the Kalixanda Study).
      METHODS: Those with endoscopic or histological findings suggestive of GERD and
      randomly half of those with NERD (n=481) were invited for follow-up investigation
      including endoscopy and a validated symptom questionnaire 5 years after the
      initial study. Multinomial logistic regression was used to estimate relative risk
      ratios (RRRs) and 95% confidence intervals (CIs) for change in presentation of
      GERD. RESULTS: Of the 405 subjects available for inclusion, endoscopy was
      performed in 284 (response rate 70.1%). The incidence of BE was 9.9/1,000 person
      years. Of those with NERD at baseline (n=113), progression to erosive esophagitis
      was found in 11; 2 developed BE. Erosive esophagitis (n=90) progressed to a more
      severe grade in 12 and to BE in 8 cases. Erosive esophagitis at baseline was
      independently associated with BE at follow-up (RRR 5.2; 95% CI 1.2-22.9).
      CONCLUSIONS: Compared with being free of GERD at follow-up, erosive esophagitis
      is a major risk factor for BE (with a fivefold increased risk) after 5 years in
      the general population.

PMID- 21946285
TI  - Development and inter-laboratory validation study of an improved new real-time
      PCR assay with internal control for detection and laboratory diagnosis of African
      swine fever virus.
AB  - A real-time polymerase chain reaction (PCR) assay for the rapid detection of
      African swine fever virus (ASFV), multiplexed for simultaneous detection of swine
      beta-actin as an endogenous control, has been developed and validated by four
      National Reference Laboratories of the European Union for African swine fever
      (ASF) including the European Union Reference Laboratory. Primers and a
      TaqMan((r)) probe specific for ASFV were selected from conserved regions of the
      p72 gene. The limit of detection of the new real-time PCR assay is 5.7-57 copies
      of the ASFV genome. High accuracy, reproducibility and robustness of the PCR
      assay (CV ranging from 0.7 to 5.4%) were demonstrated both within and between
      laboratories using different real-time PCR equipments. The specificity of virus
      detection was validated using a panel of 44 isolates collected over many years in
      various geographical locations in Europe, Africa and America, including recent
      isolates from the Caucasus region, Sardinia, East and West Africa. Compared to
      the OIE-prescribed conventional and real-time PCR assays, the sensitivity of the
      new assay with internal control was improved, as demonstrated by testing 281
      field samples collected in recent outbreaks and surveillance areas in Europe and
      Africa (170 samples) together with samples obtained through experimental
      infections (111 samples). This is particularly evident in the early days
      following experimental infection and during the course of the disease in pigs sub
      clinically infected with strains of low virulence (from 35 up to 70dpi). The
      specificity of the assay was also confirmed on 150 samples from uninfected pigs
      and wild boar from ASF-free areas. Measured on the total of 431 tested samples,
      the positive deviation of the new assay reaches 21% or 26% compared to PCR and
      real-time PCR methods recommended by OIE. This improved and rigorously validated
      real-time PCR assay with internal control will provide a rapid, sensitive and
      reliable molecular tool for ASFV detection in pigs in newly infected areas,
      control in endemic areas and surveillance in ASF-free areas.

PMID- 21946286
TI  - Development of highly sensitive assays for detection of genetic variation in key
      Helicoverpa armigera nucleopolyhedrovirus genes.
AB  - Information on the degree of genetic variation in key Helicoverpa armigera
      nucleopolyhedrovirus (HearNPV) genes is limited as the currently used techniques
      lack the detection sensitivity required to identify multiple genetic variants
      within a baculovirus population. To facilitate the detection and study of genetic
      variation within HearNPV populations, denaturing gradient gel electrophoresis
      (DGGE) assays were designed for a core baculovirus gene (DNA polymerase) and two
      core lepidopteran-specific baculovirus genes (dbp1 and me53). The gene-specific
      DGGE assays were capable of producing unique, sensitive and rapid genetic
      fingerprints of the genetic variants within a HearNPV population and were
      sensitive enough to detect as many as 26 genetic variants within a single portion
      (<500bp) of a HearNPV gene. In addition to enabling the detection of the genetic
      variation in key HearNPV genes, the DGGE assays allowed seven geographically
      distinct HearNPV populations to be differentiated on the basis of their DGGE
      profiles. The developed DGGE assays will be useful in studies that aim to
      elucidate the generation and maintenance of genetic diversity in HearNPV.

PMID- 21946287
TI  - A simple method for the parallel deep sequencing of full influenza A genomes.
AB  - Given the major threat of influenza A to human and animal health, and its ability
      to evolve rapidly through mutation and reassortment, tools that enable its timely
      characterization are necessary to help monitor its evolution and spread. For this
      purpose, deep sequencing can be a very valuable tool. This study reports a
      comprehensive method that enables deep sequencing of the complete genomes of
      influenza A subtypes using the Illumina Genome Analyzer IIx (GAIIx). By using
      this method, the complete genomes of nine viruses were sequenced in parallel,
      representing the 2009 pandemic H1N1 virus, H5N1 virus from human and H1N1 virus
      from swine, on a single lane of a GAIIx flow cell to an average depth of 122
      fold. This technique can be applied to cultivated and uncultivated virus.

PMID- 21946288
TI  - Detection of Puumala and Rift Valley Fever virus by quantitative RT-PCR and virus
      viability tests in samples of blood dried and stored on filter paper.
AB  - Haemorrhagic fever viruses cause emerging infections worldwide, and blood or
      serum is the main sample used for diagnosis. However, storage and transportation
      of such samples from remote areas to regional laboratories may be complicated and
      expensive. In this study, a novel approach was evaluated for the detection of
      Puumala hantavirus (PUUV) RNA and Rift Valley fever virus (RVFV) RNA. Whole-blood
      samples spiked with viable virus particles were tested in parallel with clinical
      samples from patients with acute haemorrhagic fever with renal syndrome
      (nephropathia epidemica). Individual blood samples were spotted on filter paper,
      dried, and used for RNA extraction at later time points. PUUV RNA was detected by
      RT-PCR after storage at room temperature for up to six weeks. In contrast, only
      low copy numbers of RVFV RNA were detected after 1-2 days even though viable RVFV
      was eluted from the dried filter papers after the same time. The use of filter
      paper to collect and store blood samples for PUUV RNA detection is therefore a
      simple and reliable procedure. This approach might facilitate sampling and
      analysis of other RNA viruses from human or animal sources and could be used for
      field studies in remote areas or in developing countries.

PMID- 21946289
TI  - TaqMan real-time PCR assay based on DNA polymerase gene for rapid detection of
      Orf infection.
AB  - Both conventional and real time PCR (rt-PCR) assays based on the amplification of
      a 103bp fragment from the DNA polymerase (DNA pol) gene (conserved, non
      structural) of Orf virus (ORFV) were developed for detection and semi
      quantitation of ORFV DNA from infected cell culture and clinical samples. The
      latter technique was based on TaqMan chemistry. The rt-PCR assay was specific and
      sensitive as it could detect as low as 3.5fg or 15 copies of ORFV genomic DNA.
      Both intra- (0.38-1.0%) and inter-assay (0.53-2.87%) variabilities of rt-PCR were
      within the acceptable range meaning the high efficiency and reproducibility of
      the assay. The rt-PCR was applied successfully to detect ORFV DNA from suspected
      clinical samples. Further, the assay has shown a relative diagnostic sensitivity
      and specificity of 100% and 93.5%, respectively, when compared to B2L gene based
      semi-nested PCR implying a wide potential of this rt-PCR for rapid field
      diagnosis of Orf in sheep and goats.

PMID- 21946291
TI  - Development of a community-based fall prevention program: Stay In Balance.
AB  - BACKGROUND: Falls and fall-related injuries are critical issues for older adults;
      evidence indicates that multidimensional interventions that address modifiable
      risk factors can be successful in reducing falls. Few evidence-based fall
      prevention interventions exist due, in part, to complex issues associated with
      development and implementation. There is a need for a variety of such programs
      from which older adults may choose. We describe steps, outcomes, and issues
      involved in developing/implementing an evidenced-based fall prevention program in
      community settings. METHODS: The Stay In Balance program (SIB), developed by a
      team of professionals, local service providers and active older adults, was
      carried out with total of 135 older adults in several steps: developing
      objectives and program content, laboratory-based randomized controlled trial
      (RCT), pilot program in the community, community-based RCT, and implementation at
      2 community sites. RESULTS: Each step in development provided useful and
      different insights into needed changes in program content, equipment, support
      materials, training, and appropriate outcome measures. CONCLUSION: Development of
      an evidenced-based fall prevention program requires a long term commitment on the
      part of all partners, University personnel, local service providers, and older
      adult participants; funding is also critical.

PMID- 21946290
TI  - Validation of an r3AB1-FMDV-NSP ELISA to distinguish between cattle infected and
      vaccinated with foot-and-mouth disease virus.
AB  - Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed
      livestock which has a drastic economic impact for affected countries. Although
      FMDV is distributed worldwide, many regional programs have been effective
      eradicating this agent. In Argentina, as in many other regions of South America,
      the combination of a systematic vaccination plan, together with an effective
      detection system capable of differentiating infection from vaccination, has been
      successful for eradicating this agent from the country. The properties of
      recombinant 3AB1 FMDV non-structural protein (r3AB1 FMDV-NSP), as a marker for
      the detection of antibodies to differentiate between cattle infected and
      vaccinated with FMDV, have been described previously. The goal of the present
      study was to validate the 3AB1 ELISA using a well characterized serum panel from
      Argentina (n=559) including eight national and one international reference sera.
      Overall, the 3AB1 ELISA demonstrated good feasibility, repeatability,
      reproducibility, analytical sensitivity and specificity, and accuracy. The
      results from the 3AB1 ELISA when compared with those obtained from the OIE index
      test (NCPanaftosa screening) showed a similar performance of both tests
      [diagnostic sensitivity=84% (C.I.=79-88%) and 80% (C.I.=75-85%), respectively;
      and diagnostic specificity=98.6% (C.I.=97-100%) and 95% (C.I.=91-98%),
      respectively]. The present work proposes the 3AB1 ELISA as an alternative to
      imported kits for FMD internal screening and transboundary sero-surveillance.

PMID- 21946293
TI  - Cytokine profiles in cyst fluids from ovarian tumors reflect immunosuppressive
      state of the tumor.
AB  - OBJECTIVE: Ovarian tumors, both benign and malignant, often contain cystic
      lesions. Analysis of cytokine levels of this enclosed fluid may be a pure way to
      study cytokine expression to gain more insight in tumor-host interaction.
      METHODS: We analyzed the expression of cytokines in 45 cyst fluids from benign
      and malignant ovarian tumors and mapped the cytokine profiles for the different
      histological subgroups. The concentration of interleukin (IL)-1beta, IL-2, IL-4,
      IL-5, IL-6, IL-8, IL-10, IL-12p70, interferon gamma, tumor necrosis factor alpha,
      tumor necrosis factor beta, transforming growth factor beta, and C-C motif
      chemokine 22 was measured. RESULTS: The presence of IL-6 in cyst fluid is
      correlated with malignancy. IL-8 was also expressed in benign samples, but the
      levels were significantly higher in malignant cyst fluids. Transforming growth
      factor beta was only present in latent form in both benign and malignant cyst
      fluids. C-C motif chemokine 22 was detectable in higher levels in mucinous
      samples than in serous samples. IL-10 was not expressed in cyst fluid. T helper 1
      subtype (TH1: IL-12 and IFN-gamma) and TH2 (IL-4, IL-5) cytokines were similarly
      expressed in malignant and benign mucinous tumors. However, in the serous group,
      TH1 and TH2 cytokines were expressed in the benign samples but not in the
      malignant samples. In the high-grade malignant serous group, we found an inverse
      relationship between IL-8 levels and overall survival. CONCLUSIONS: Our results
      suggest that the immunosuppressive state created by ovarian cancer is reflected
      in the cystic fluid within the tumor. Furthermore, our findings suggest that type
      1 and type 2 tumors have a distinct immunological profile and support the
      dualistic model for ovarian tumorigenesis.

PMID- 21946294
TI  - Why southeastern Nigerian women who are aware of cervical cancer screening do not
      go for cervical cancer screening.
AB  - OBJECTIVE: This study aimed to evaluate reasons behind nonuptake of cervical
      cancer screening by women who are aware of cervical cancer screening in southeast
      Nigeria. METHOD: Women attending gynecologic clinics of 3 health institutions in
      Enugu, Nigeria, were interviewed by means of a questionnaire to determine those
      who were aware of cervical cancer screening. The biodemographic characteristics
      and level of knowledge of cervical cancer screening of women who underwent a
      previous screen were compared with those of women who did not undergo a previous
      screen. Reasons for nonuptake of cervical cancer screening as well as potential
      reasons for undertaking cervical cancer screening were also extracted. RESULTS: A
      total of 3712 women were interviewed. Of these respondents, 2048 (55.2%) were
      aware of cervical cancer screening.Only 19.0% of those who were aware of cervical
      cancer screening underwent a previous screen. Level of knowledge of cervical
      cancer prevention, university education, and age had a significant impact on the
      uptake of cervical cancer screening. Poor health-seeking behavior and fear of
      violation of privacy are the major reasons for nonuptake of cervical cancer
      screening. Potential reasons for uptake of cervical cancer screening include
      development of symptoms, adequate educative information, and physician's
      recommendation. CONCLUSIONS: Women in southern Nigeria do not go for cervical
      cancer screening because of poor understanding of cervical cancer prevention,
      feeling of violation of the privacy of their genitals, and poor health-seeking
      behavior. There is a need to modify current policy approaches to cervical cancer
      prevention in Nigeria. Policies that will address the privacy violation fears and
      poor health-seeking behavior of the Nigerian woman as well improve the level of
      educative information on cervical cancer prevention need to be evolved.

PMID- 21946295
TI  - Is differentiated vulval intraepithelial neoplasia the precursor lesion of human
      papillomavirus-negative vulval squamous cell carcinoma?
AB  - Vulval squamous cell carcinoma appears to arise via 2 distinct pathways. A
      significant minority are associated with oncogenic human papillomavirus (HPV)
      infection and undifferentiated vulval intraepithelial neoplasia (VIN). However,
      the majority arises in the absence of HPV, on a background of chronic
      inflammation. Until recently, it was assumed that lichen sclerosus was the
      underlying inflammatory condition in the majority of HPV-negative cancers. This
      pathway of carcinogenesis has been less well studied than the HPV pathway.
      Emerging evidence implicates differentiated VIN (DVIN), rather than lichen
      sclerosus, as the most likely precursor lesion in HPV-negative vulval squamous
      cell carcinoma. Here we discuss the clinical and molecular evidence that
      implicates DVIN as a lesion with a high malignant potential. This lesion is
      probably underdiagnosed and may be undertreated. Better recognition of DVIN by
      gynecologists and pathologists may therefore offer an opportunity to prevent some
      vulval cancers.

PMID- 21946296
TI  - Immediate antecedents of marijuana use: an analysis from ecological momentary
      assessment.
AB  - BACKGROUND AND OBJECTIVES: Marijuana remains the most commonly used illicit
      substance. Marijuana craving, anxiety, and peer marijuana use are thought to play
      important roles in the etiology and maintenance of marijuana use. The present
      study aimed to identify patterns between marijuana use and these affective and
      situational risk factors in the natural environment. METHODS: The sample
      consisted of 49 current marijuana users (38.8% female), 63.2% of whom evinced a
      current cannabis use disorder. Ecological momentary assessment was used to
      collect multiple daily ratings of marijuana craving, state anxiety, and peer
      marijuana use over two weeks. Mixed effects linear models were used to examine
      within- and between-day antecedents, correlates, and consequences of marijuana
      use. RESULTS: Between-day analyses indicated that marijuana use days were
      associated with higher marijuana craving but lower state anxiety. Within-day
      analyses confirmed that marijuana craving was higher prior to marijuana use and
      lower following use. Anxiety was related to marijuana craving. Although anxiety
      was somewhat higher prior to marijuana use, it did not decrease significantly
      following use. The vast majority of marijuana use occurred when others were also
      using marijuana. LIMITATIONS: The sample was comprised of college students, a
      group at particular risk for marijuana use and use-related problems. Future work
      is necessary to determine whether results generalize to other populations.
      CONCLUSIONS: These data support the contention that marijuana craving, anxiety,
      and peer use play important roles in the maintenance of marijuana use.

PMID- 21946297
TI  - Disgust propensity in obsessive-compulsive disorder: cross-sectional and
      prospective relationships.
AB  - BACKGROUND AND OBJECTIVES: Findings from non-clinical samples suggest that
      disgust propensity is associated with contamination concerns in obsessive
      compulsive disorder (OCD). However, studies of clinical samples have yielded
      conflicting results. We investigated the relationship between disgust propensity
      and OCD symptoms in a clinical sample and examined whether changes in disgust
      propensity are associated with changes in OCD symptoms. METHODS: One hundred and
      nine OCD participants completed measures of disgust propensity and OCD symptoms.
      Sixty of these underwent a six-month follow-up assessment. RESULTS: At the
      baseline assessment, disgust propensity was associated with all OCD symptom
      dimensions except hoarding. Changes in overall disgust propensity between
      baseline and the six-month follow-up assessment were associated with changes in
      overall self-reported OCD symptoms but not with changes in contamination-based
      OCD symptoms or changes in interviewer-assessed OCD symptoms. LIMITATIONS: There
      was substantial participant attrition between the baseline and follow-up
      assessments. CONCLUSIONS: Our study is the first to investigate prospective
      relationships between disgust propensity and OCD across a six-month interval. Our
      findings suggest that if there is an association between changes in disgust
      propensity and changes in contamination-based OCD symptoms its magnitude is
      likely to be small.

PMID- 21946298
TI  - Role of microRNAs in endothelial cell pathophysiology.
AB  - MicroRNAs (miRNAs) are a family of small, noncoding RNAs that repress gene
      expression at the post-transcriptional level. Over 700 miRNAs have been
      identified in the human genome, of which 20% to 30% regulate human protein-coding
      genes. Functional in vitro studies have shown that miRNAs are critical for
      endothelial cell gene expression and function. miRNAs were found in
      atherosclerosis, cardiac hypertrophy, arterial hypertension, coronary artery
      disease, diabetes, and inflammatory diseases. We review the current knowledge
      about the role of miRNAs in endothelial cells with emphasis on the regulation of
      cellular senescence, angiogenesis, and vascular inflammation. It has been shown
      that miR-34a, miR-217, miR-200, miR-146c, and miR-181a are responsible for the
      regulation of cell stress and proliferation processes. Proangiogenic factors
      include miR-130a, miR-210, miR-424, miR-17-92, miR-27-b, let-7f, and miR-217,
      while miR-221 and miR-222 have antiangiogenic properties. Other known miRNAs,
      including miR-31, miR17-3p, miR-155, miR-221, miR-222, and miR-126, are important
      factors in the regulation of vascular inflammation. Studies show that miRNA
      expression analysis can be used in the diagnosis and treatment of various
      diseases; however, additional research is needed before it is used in routine
      clinical setting.

PMID- 21946299
TI  - Incorporating personalized gene sequence variants, molecular genetics knowledge,
      and health knowledge into an EHR prototype based on the Continuity of Care Record
      standard.
AB  - OBJECTIVES: The current volume and complexity of genetic tests, and the molecular
      genetics knowledge and health knowledge related to interpretation of the results
      of those tests, are rapidly outstripping the ability of individual clinicians to
      recall, understand and convey to their patients information relevant to their
      care. The tailoring of molecular genetics knowledge and health knowledge in
      clinical settings is important both for the provision of personalized medicine
      and to reduce clinician information overload. In this paper we describe the
      incorporation, customization and demonstration of molecular genetic data (mainly
      sequence variants), molecular genetics knowledge and health knowledge into a
      standards-based electronic health record (EHR) prototype developed specifically
      for this study. METHODS: We extended the CCR (Continuity of Care Record), an
      existing EHR standard for representing clinical data, to include molecular
      genetic data. An EHR prototype was built based on the extended CCR and designed
      to display relevant molecular genetics knowledge and health knowledge from an
      existing knowledge base for cystic fibrosis (OntoKBCF). We reconstructed test
      records from published case reports and represented them in the CCR schema. We
      then used the EHR to dynamically filter molecular genetics knowledge and health
      knowledge from OntoKBCF using molecular genetic data and clinical data from the
      test cases. RESULTS: The molecular genetic data were successfully incorporated in
      the CCR by creating a category of laboratory results called "Molecular Genetics"
      and specifying a particular class of test ("Gene Mutation Test") in this
      category. Unlike other laboratory tests reported in the CCR, results of tests in
      this class required additional attributes ("Molecular Structure" and "Molecular
      Position") to support interpretation by clinicians. These results, along with
      clinical data (age, sex, ethnicity, diagnostic procedures, and therapies) were
      used by the EHR to filter and present molecular genetics knowledge and health
      knowledge from OntoKBCF. CONCLUSIONS: This research shows a feasible model for
      delivering patient sequence variants and presenting tailored molecular genetics
      knowledge and health knowledge via a standards-based EHR system prototype. EHR
      standards can be extended to include the necessary patient data (as we have
      demonstrated in the case of the CCR), while knowledge can be obtained from
      external knowledge bases that are created and maintained independently from the
      EHR. This approach can form the basis for a personalized medicine framework, a
      more comprehensive standards-based EHR system and a potential platform for
      advancing translational research by both disseminating results and providing
      opportunities for new insights into phenotype-genotype relationships.

PMID- 21946300
TI  - Human cytochrome-P450 enzymes metabolize N-(2-methoxyphenyl)hydroxylamine, a
      metabolite of the carcinogens o-anisidine and o-nitroanisole, thereby dictating
      its genotoxicity.
AB  - N-(2-Methoxyphenyl)hydroxylamine is a component in the human metabolism of two
      industrial and environmental pollutants and bladder carcinogens, viz. 2
      methoxyaniline (o-anisidine) and 2-methoxynitrobenzene (o-nitroanisole), and it
      is responsible for their genotoxicity. Besides its capability to form three
      deoxyguanosine adducts in DNA, N-(2-methoxyphenyl)-hydroxylamine is also further
      metabolized by hepatic microsomal enzymes. To investigate its metabolism by human
      hepatic microsomes and to identify the major microsomal enzymes involved in this
      process are the aims of this study. N-(2-Methoxyphenyl)hydroxylamine is
      metabolized by human hepatic microsomes predominantly to o-anisidine, one of the
      parent carcinogens from which N-(2-methoxyphenyl)hydroxylamine is formed, while o
      aminophenol and two N-(2-methoxyphenyl)hydroxylamine metabolites, whose exact
      structures have not been identified as yet, are minor products. Selective
      inhibitors of microsomal CYPs, NADPH:CYP reductase and NADH:cytochrome-b(5)
      reductase were used to characterize human liver microsomal enzymes reducing N-(2
      methoxyphenyl)hydroxylamine to o-anisidine. Based on these studies, we attribute
      the main activity for this metabolic step in human liver to CYP3A4, 2E1 and 2C
      (more than 90%). The enzymes CYP2D6 and 2A6 also partake in this N-(2
      methoxyphenyl)hydroxylamine metabolism in human liver, but only to ~6%. Among the
      human recombinant CYP enzymes tested in this study, human CYP2E1, followed by
      CYP3A4, 1A2, 2B6 and 2D6, were the most efficient enzymes metabolizing N-(2
      methoxyphenyl)hydroxylamine to o-anisidine. The results found in this study
      indicate that genotoxicity of N-(2-methoxyphenyl)hydroxylamine is dictated by its
      spontaneous decomposition to nitrenium/carbenium ions generating DNA adducts, and
      by its susceptibility to metabolism by CYP enzymes.

PMID- 21946301
TI  - Effect of surface coating on the biodistribution profile of gold nanoparticles in
      the rat.
AB  - Successful application of gold nanoparticles (AuNPs) in biomedicine requires
      extensive safety assessment for which biokinetic studies are crucial. We
      evaluated the biodistribution of AuNPs (~20 nm) with different surface coatings:
      citrate, 11-MUA and 3 pentapeptides, CALNN, CALND and CALNS, after i.v.
      administration to rats (0.6-1 mg Au/kg). Biodistribution was evaluated based on
      Au tissue content measured by GFAAS. Citrate-AuNPs were rapidly removed from
      circulation with 60% of the injected dose depositing in the liver. Thirty minutes
      post-injection, the lungs presented about 6% of the injected dose with levels
      decreasing to 0.7% at 24 h. Gold levels in the spleen were of 2.6%. After 24 h,
      liver presented the highest Au level, followed by spleen and blood. A similar
      biodistribution profile was observed for MUA-coated AuNPs compared to Cit-AuNPs
      at 24h post-injection, while significantly higher levels of peptide-capped AuNPs
      were found in the liver (74-86%) accompanied by a corresponding decrease in blood
      levels. TEM analysis of liver slices showed AuNPs in Kupffer cells and
      hepatocytes, trapped inside endosomes. Our data demonstrate that AuNPs are
      rapidly distributed and that the liver is the preferential accumulation organ.
      Peptide capping significantly increased hepatic uptake, showing the influence of
      AuNPs functionalization in biodistribution.

PMID- 21946303
TI  - Hypercoagulability in patients with chronic noncirrhotic portal vein thrombosis.
AB  - BACKGROUND & AIMS: Although they have normal liver histology and function,
      patients with chronic noncirrhotic nontumoral portal vein thrombosis (NC-PVT)
      frequently have abnormal results from coagulation tests. We investigated the
      significance of these results. METHODS: We analyzed blood samples collected from
      50 stable patients with NC-PVT secondary to a thrombophilic disorder (32%) or
      local factor (32%), or that was idiopathic (36%). We measured endogenous thrombin
      potential (ETP) with and without thrombomodulin, prothrombin time, activated
      partial thromboplastin time, coagulation factors (I, II, V, VII, VIII, IX, X, XI,
      and XII), antithrombin, proteins C and S, von Willebrand factor (vWF) antigen,
      vWF ristocetin cofactor, a disintegrin and metalloprotease with thrombospondin
      type 1 motifs 13 antigen, D-dimer, plasmin-antiplasmin complex, prothrombin
      fragment F1+2, activated factor VII, and clot lysis time. Samples from 50 age-
      and sex-matched healthy individuals were evaluated as controls. RESULTS: Compared
      with controls, patients with NC-PVT had significant increases in prothrombin time
      and activated partial thromboplastin time; they had significant reductions in
      levels of procoagulant factors II, V, VII, IX, X, XI, and XII, and the
      anticoagulants antithrombin, protein C, and protein S. The patients had increased
      levels of factor VIII and vWF antigen. Irrespective of etiology, patients with NC
      PVT had a significant increase in ETP with thrombomodulin and higher levels of
      factor VIIa, prothrombin fragment F1+2, D-dimer, and plasmin-antiplasmin complex
      than controls, indicating in vivo activation of coagulation and fibrinolysis.
      CONCLUSIONS: Patients with NC-PVT have hypercoagulability that is independent of
      the underlying etiology, based on in vitro analyses of thrombin-generation
      capacity and increased levels of biomarkers in blood samples. Further studies are
      required to determine if activation of hemostasis increases the risk for
      thrombotic events.

PMID- 21946304
TI  - Health-related physical fitness is associated with selected sociodemographic and
      behavioral factors in Brazilian school children.
AB  - BACKGROUND: This study investigated the association between sociodemographic and
      behavioral factors and health standards based on physical fitness component
      scores in a sample of Brazilian schoolchildren. METHODS: A sample of 1457 girls
      and 1392 boys aged 6 to 18 years performed a test battery of 5 items: 1) sit-and
      reach, 2) curl-up, 3) trunk-lift, 4) push-up, and 5) progressive endurance run
      (PACER). The cut-off scores for gender and age suggested by the FitnessGram were
      adopted. RESULTS: The findings showed that the sociodemographic and behavioral
      factors significantly associated with the ability of schoolchildren of meeting
      the health standards varied according to the fitness test. In the 5 tests used
      girls presented lower chance of meeting the health standards. Age and
      socioeconomic class were negatively associated with the performance in all
      physical tests. Schoolchildren aged <= 9 years or from families of lowest
      socioeconomic class presented approximately twice the chance of meeting the
      health standards than those aged >= 15 years and from more privileged families,
      specifically in the push-up (OR = 2.40; 95% CI 2.01-2.82) and PACER (OR = 2.18;
      95% CI 1.84-2.54) tests. CONCLUSIONS: Interventions to promote health-related
      physical fitness should not only consider gender and age of schoolchildren, but
      also selected sociodemographic and behavioral factors, especially socioeconomic
      class and leisure activities.

PMID- 21946305
TI  - Background and rationale for mechanism of action, efficacy, and safety of
      fingolimod (Gilenya), the first oral therapy for remitting-relapsing multiple
      sclerosis:  with special emphasis upon visual safety.

PMID- 21946306
TI  - Radiology update in neuro-ophthalmology.
AB  - PURPOSE OF REVIEW: Radiologic imaging is indispensible for the diagnosis and
      management of many neuro-ophthalmologic conditions. Advances in the radioimaging
      of neuro-ophthalmologic disorders may evolve from the clinical or the
      radiological side, meaning there is a constant stream of new information for the
      clinician. RECENT FINDINGS: Functional MRI, diffusion tensor MRI, magnetization
      transfer imaging, and magnetic resonance spectroscopy are examples of nonstandard
      radiographic techniques, which have expanded the knowledge of neuro
      ophthalmologic conditions. Studies using conventional MRI have also led to
      advances in understanding optic neuropathies, the ocular motor system,
      pseudotumor cerebri, posterior reversible encephalopathy syndrome and migraine.
      SUMMARY: This article discusses recent radiologic advances relevant to neuro
      ophthalmology.

PMID- 21946307
TI  - The role of neurotensin in passive avoidance learning in the rat central nucleus
      of amygdala.
AB  - Tridecapeptide neurotensin (NT) acts as a neurotransmitter and/or neuromodulator
      and plays a role in learning and reinforcement. The central nucleus of amygdala
      (CeA), which is relatively rich in NT and neurotensin-1 receptors (NTS1),
      participates in the regulation of memory and learning mechanisms. The aim of this
      study was to examine the possible effect of NT and NTS1 antagonist (ANT) on
      passive avoidance learning after their microinjection into the CeA of male wistar
      rats. NT significantly increased the latency time. Effect of NT was blocked by
      ANT pretreatment. ANT in itself had no effect. Our results show that in the rat
      CeA NT facilitates passive avoidance learning via NTS1.

PMID- 21946308
TI  - Significance of serum glucocorticoid and chelatable zinc in depression and
      cognition in zinc deficiency.
AB  - Dietary zinc deficiency elicits neuropsychological symptoms and cognitive
      dysfunction. To pursue the mechanisms of these symptoms, in the present study,
      the relationship among serum glucocorticoid, chelatable zinc in the synaptic
      cleft and brain function based on behavior was examined in young rats fed a zinc
      deficient diet for 4 weeks. Serum glucocorticoid level was significantly
      increased in zinc-deficient rats. However, the induction of in vivo dentate gyrus
      LTP and object recognition memory were not affected in zinc-deficient rats.
      Chelatable zinc levels were decreased in the stratum lucidum of the hippocampal
      CA3, but not in the molecular layer of the dentate gyrus. It is reported that
      dentate gyrus LTP and object recognition memory are affected in clioquinol
      (30mg/kg)-administered rats, in which chelatable zinc is significantly decreased
      in the molecular layer of the dentate gyrus. Thus, the significant decrease in
      chelatable zinc in the molecular layer of the dentate gyrus may be required for
      object recognition memory deficit in zinc deficiency. On the other hand, the time
      of grooming in the open-field test was decreased in zinc-deficient rats.
      Immobility time in the forced swim test was increased in zinc-deficient rats, but
      not in clioquinol-administered rats, in which chelatable zinc was more markedly
      decreased than in zinc-deficient rats, suggesting that the lack of chelatable
      zinc does not increase depression-like behavior. These results suggest that the
      chronic increase in serum glucocorticoid level is involved in the increase in
      depression-like behavior rather than the decrease in chelatable zinc after 4-week
      zinc deficiency.

PMID- 21946310
TI  - Unilateral nigrostriatal 6-hydroxydopamine lesions in mice II: predicting l-DOPA
      induced dyskinesia.
AB  - In the 6-hydroxydopamine (6-OHDA) lesioned rodent the location of the lesion
      produces significantly different behavioural phenotypes, responses to the
      dopamine precursor l-3,4-dihydroxyphenylalanine (l-DOPA) and neuropathology.
      Lesion extent is commonly determined by a series of motor tests, but whether any
      of these tests have a relationship to the development and predictability of
      dyskinesia is unknown. We used mice with 6-OHDA lesions of the striatum, medial
      forebrain bundle and substantia nigra to examine the relationship between a range
      of tests used to determine motor function in the absence of l-DOPA: rotarod,
      cylinder, corridor, the balance beam, locomotor activity, psycho-stimulant and
      spontaneous rotational behaviour. The mice were subsequently treated with l-DOPA
      in progressively increasing doses and the development of l-DOPA-induced
      dyskinesia assessed. Most of these tests predict dopamine depletion but only
      rotarod, spontaneous rotations, apomorphine-induced rotations and locomotor
      activities were significantly correlated with the development of dyskinesia at
      6mg/kg and 25mg/kg l-DOPA. The losses of dopaminergic neurons and serotonergic
      density in the ventral and dorsal striatum were dependent upon lesion type and
      were also correlated with l-DOPA-induced dyskinesia. The expression of
      FosB/DeltaFosB was differentially affected in the striatum and nucleus accumbens
      regions in dyskinetic mice according to lesion type.

PMID- 21946309
TI  - Type 1 5alpha-reductase may be required for estrous cycle changes in affective
      behaviors of female mice.
AB  - There are estrous cycle differences in affective behaviors of rodents that are
      generally attributed to cyclic variations in estradiol, progesterone (P) and its
      metabolites. A question is the role of the steroid metabolism enzyme, 5alpha
      reductase, for these estrous cycle differences. To address the requirement of
      5alpha-reductase, estrous cycle variations in the behavior of wildtype mice and
      their littermates that are deficient in the 5alpha-reductase type 1 enzyme
      (5alphaRKO mice) were examined. The hypothesis was that if some of the estrous
      cycle differences in exploratory (open field) and anxiety (elevated plus maze)
      are due to P's 5alpha-reduction to 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha
      THP), then wildtype mice will have estrous cycle differences in the expression of
      these behaviors, but 5alphaRKO mice will not. Mice were tested in these tasks and
      then had plasma and brains collected so that steroid levels (estradiol, P,
      3alpha,5alpha-THP, corticosterone) could be measured in these tissues. Results
      supported this hypothesis. There were estrous cycle differences among wildtype,
      but not 5alphaRKO, mice. Proestrous wildtype mice made more central entries in
      the open field and spent more time on the open arms of the plus maze, coincident
      with higher 3alpha,5alpha-THP levels in plasma and brain regions important for
      these behaviors, such as the hippocampus and cortex, compared to their diestrous
      counterparts. Variability in the open field and elevated plus maze could be
      explained by circulating and hippocampus levels of 3alpha,5alpha-THP,
      respectively. Thus, 5alpha-reductase may be required for the estrous cycle
      variations in affective behavior and 3alpha,5alpha-THP levels of female mice.

PMID- 21946311
TI  - FOCUS ON...metastasis suppressors.

PMID- 21946312
TI  - Glucocorticoid suppresses BDNF-stimulated MAPK/ERK pathway via inhibiting
      interaction of Shp2 with TrkB.
AB  - Increased glucocorticoids (GCs) have been implicated in the pathophysiology of
      depressive disorder. We previously found that dexamethasone (DEX, a synthetic GC)
      repressed brain-derived neurotrophic factor (BDNF)-induced synaptic proteins via
      suppressing extracellular signal-regulated protein kinase (ERK) signaling. Here,
      we investigated the possible involvement of Src homology-2 domain-containing
      phosphatase2 (Shp2), an ERK signaling mediator. We found that DEX suppressed Shp2
      interaction with TrkB, a receptor for BDNF, in cultured cortical neurons.
      NSC87877, a Shp2 inhibitor, mimicked DEX, and Shp2 overexpression reversed the
      effect of DEX, suggesting that GCs suppress ERK signaling through inhibiting the
      interaction of Shp2 with TrkB.

PMID- 21946313
TI  - Subtherapeutic serum vancomycin concentrations during on-line hemodiafiltration.
AB  - The aim of the study is to study vancomycin serum concentration changes during on
      line hemodiafiltration (OL-HDF) and determine whether administration of
      vancomycin during the last hour of OL-HDF provides therapeutic serum
      concentrations. Vancomycin was administered intravenously at a dose of 15 mg/kg
      to 17 chronic hemodialysis patients who were enrolled into two study groups (A
      and B). In group A patients (n = 11), vancomycin was administered immediately
      postdialysis. Forty-three hours later, a 4-hour OL-HDF session was performed.
      Blood samples (S) for vancomycin measurement were drawn before, during, and after
      the session. In group B patients (n = 6), vancomycin was administered during the
      last hour of a 4-hour OL-HDF session on Monday. Vancomycin serum concentrations
      were measured postdialysis, as well as before and after the next two dialysis
      sessions of the week. In group A patients, mean vancomycin concentrations were
      reduced by 50% (S(pre): 10.2 +/- 1.4 MUg/ml, S(post): 5.0 +/- 0.9 MUg/ml).
      Vancomycin dialysance was 74.6 +/- 29.3 ml/min, while the volume of distribution
      was 0.42 L/kg. In group B patients, mean vancomycin concentrations before the
      beginning of Wednesday and Friday dialysis sessions were 3.1 +/- 0.7 and 1.4 +/-
      0.4 MUg/ml, respectively. Postdialysis administration of vancomycin followed by
      OL-HDF resulted in a 50% reduction of vancomycin serum concentrations.
      Administration during the last treatment hour of OL-HDF results in subtherapeutic
      vancomycin serum concentrations over the course of the subsequent inter- and
      intradialytic intervals.

PMID- 21946314
TI  - Successful liver transplantation after 21 days of hepatic coma.
AB  - A 52-year-old women was treated after ingestion of different wild mushrooms. The
      case demonstrates that successful liver transplantation with full recovery of
      brain functions is possible even after 3 weeks of persisting severe hepatic
      encephalopathy.

PMID- 21946315
TI  - Radiofrequency catheter ablation and antiarrhythmic drug therapy: a prospective,
      randomized, 4-year follow-up trial: the APAF study.
AB  - BACKGROUND: Information on comparative outcome between radiofrequency catheter
      ablation (RFA) and antiarrhythmic drugs (AADs) >1 year after randomization is
      important for clinical decision-making. METHODS AND RESULTS: A total of 198
      patients (age, 56 +/- 10 years) with paroxysmal atrial fibrillation were randomly
      assigned to RFA (99 patients) or to AADs (99 patients). We evaluated efficacy of
      RFA or AADs in a comparable 48-month follow-up period according to intention-to
      treat analysis. Cardiac rhythm was assessed with daily transtelephonic
      transmissions. Quality of life was also analyzed. At 4 years, among the 99
      patients first assigned to RFA, the procedure was repeated because of recurrent
      atrial fibrillation/atrial tachycardia in 27 patients (27.3%). Among the 99
      patients randomly assigned to AADs, 87 (87.9%) crossed over to undergo RFA and 4
      years after random assignment only 12 (12.1%) were in sinus rhythm with AAD alone
      without ablation. Despite the high level of crossovers, at 4 years the intention
      to-treat analysis showed that 72.7% of patients in the ablation arm and 56.5% of
      those initially randomly assigned to AADs were free of recurrent atrial
      fibrillation/atrial tachycardia (P=0.017). During the follow-up, 19.2% of AAD
      patients progressed to persistent atrial fibrillation before switching to RFA.
      RFA significantly improved quality of life (P<0.001), whereas before crossing
      over to RFA, patients receiving AADs showed poorer quality of life. Except for
      new left atrial tachycardia, there were no serious complications caused by RFA.
      CONCLUSIONS: With follow-up extended to 4 years after randomly assigned, ablation
      remains superior to antiarrhythmic drug in these patients with paroxysmal atrial
      fibrillation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov.
      Unique identifier: NCT00340314.

PMID- 21946316
TI  - Efficacy of low interatrial septum and right atrial appendage pacing for
      prevention of permanent atrial fibrillation in patients with sinus node disease:
      results from the electrophysiology-guided pacing site selection (EPASS) study.
AB  - BACKGROUND: The role of pacing sites and atrial electrophysiology on the
      progression of atrial fibrillation (AF) to the permanent form in patients with
      sinus node dysfunction (SND) has never been investigated. The aim of the study
      was to investigate the relationship between atrial electrophysiology and the
      efficacy of atrial pacing at the low interatrial septum (IAS) or at the right
      atrial appendage (RAA) to prevent persistent/permanent AF in patients with SND.
      METHODS AND RESULTS: The Electrophysiology-Guided Pacing Site Selection (EPASS)
      Study was a prospective, controlled, randomized study. Atrial refractoriness,
      basal and incremental conduction times from the RAA to the coronary sinus ostium
      were measured before implantation, and the difference (DeltaCTos) was calculated.
      Patients with DeltaCTos >= 50 ms (study group) and those with DeltaCTos <50 ms
      (control group) were randomly assigned to RAA or IAS with algorithms for
      continuous atrial stimulation "on." The primary end point was time to development
      of permanent or persistent AF within a 2-year follow-up in the study group, IAS
      versus RAA. Data were analyzed by intention to treat. One hundred two patients
      (77 +/- 7 years, 44 mol/L) were enrolled, 69 (68%) in the study group and 33
      (32%) in the control group. Of these, 97 ended the study, respectively, randomly
      assigned: 29 IAS versus 36 RAA and 18 IAS versus 14 RAA. After a mean follow-up
      of 15 +/- 7 (median, 17) months, 11 (16.6%) patients in the study group met the
      primary end point: 2 IAS versus 9 RAA (log rank=3.93, P=0.047). CONCLUSIONS: In
      patients with SND and intra-atrial conduction delay, low IAS pacing was superior
      to RAA pacing in preventing progression to persistent or permanent AF. CLINICAL
      TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier:
      NCT00239226.

PMID- 21946317
TI  - Quality of life in patients with multiple sclerosis:  the impact of depression,
      fatigue, and disability.
AB  - AIM: The aim of this study was to assess the quality of life (QoL) in patients
      with multiple sclerosis (MS), and to evaluate its association with disability and
      psychosocial factors especially depression and fatigue. METHODS: Demographic
      characteristics, education level, disease severity, and disease duration were
      documented for each patient. QoL, fatigue level, cognitive status, and depression
      level of patients were assessed by Multiple Sclerosis Quality of Life-54, Fatigue
      Severity Scale, Mini Mental State Scale, and Beck Depression Inventory,
      respectively. RESULTS: Seventy-nine patients with MS were included in the study.
      There was a moderate degree of impairment in the QoL scores of MS patients. The
      most affected parts of QoL were included: role limitation-related physical and
      emotional problems and physical and social functions. Both physical and mental
      health components of QoL showed a positive correlation with the educational level
      and employment status; a negative correlation with the level of disability,
      fatigue, and depression. Depression, disability level, and fatigue were the
      strongest variables associated with QoL, and the most important predictor of QoL
      was depression. CONCLUSION: Our results have shown that both physical and mental
      health components of QoL were negatively affected by MS. The most important
      predictor of QoL was depression followed by disability and fatigue. To improve
      the QoL for MS patients, in addition to physical disability, the influences of
      depression and fatigue on QoL should be taken into consideration.

PMID- 21946318
TI  - Validation of sterilization procedures and usage of biological indicators in the
      manufacture of healthcare products.
AB  - Healthcare product manufacturers strive to provide safe, sterile products by
      validating and controlling manufacturing procedures. Validation study is the
      result of a multidisciplinary team effort. This successful effort relies on each
      discipline understanding the fundamentals of each technical disciplines and
      applying those fundamentals in terms of their own technical background. This
      paper is to introduce the basic concepts of sterilization methodology which are
      involved in validating various technical methods of sterilization and biological
      indicators (BIs). These will mainly address sterilization procedures in general
      terms and highlight on their microbiological aspects. The proper starting point
      is defining what sterility is and how it can be achieved through the validation
      studies by using BI.

PMID- 21946319
TI  - Antimicrobial characteristics of heated scallop shell powder and its application.
AB  - Scallop shells are used to make food additives and plastering and paving
      materials. However, most of the shell is considered commercial waste. In scallop
      harvesting districts, large numbers of shells are heaped near the seaside, which
      creates problems such as offensive odors and soil pollution from heavy metals
      that leach out of the viscera. Therefore, new applications for scallop shells
      need to be developed. The main component of scallop shells is calcium carbonate
      (CaCO(3)), which is converted to calcium oxide (CaO) when heated. Heated scallop
      shell powder (HSSP) possesses broad antimicrobial action against the vegetative
      cells of bacteria, spores, and fungi. HSSP applied to fresh vegetables and
      processed foods reduces the number of viable bacterial cells. The use of HSSP in
      food processing provides a source of minerals and prolongs the shelf life of
      foodstuffs. Moreover, reducing the amount of scallop shell waste would reduce the
      related pollution problem. This report is a review of the antibacterial activity
      of HSSP and its application for the control of microbes.

PMID- 21946320
TI  - Genotyping and chlorine-resistance of Methylobacterium aquaticum isolated from
      water samples in Japan.
AB  - For microbial ecological analysis, 14 strains of Methylobacterium aquaticum
      isolated from water samples were subjected to clustering analysis on the basis of
      ribotyping and RAPD-PCR tests. The ribopatterns after digestion with EcoRI
      obtained from 14 strains of M. aquaticum were used to divide the strains into two
      groups (Groups I and II) with a similarity of 55%. From the analysis of RAPD
      patterns using primer 208, the 14 strains were divided into 3 groups (A-C) based
      on a homology of 45% or greater, and from that using primer 272, there were 4
      groups (A-D) based on a homology of 50% or greater. The chlorine resistance
      (99.9% CT values) of these isolates was also experimentally confirmed, and we
      attempted to define the connection between chlorine resistance and the geno
      cluster. The average CT value of group I was 0.89 mg*min/l and the average of
      group II was 0.69 mg*min/l. No remarkable differences in the CT values for the
      groups were found.

PMID- 21946321
TI  - Removal of viable bacteria and endotoxins by Electro Deionization (EDI).
AB  - Viable bacteria and endotoxins in water sometimes cause problems for human
      health. Endotoxins are major components of the outer cell wall of gram-negative
      bacteria (lipopolysaccharides). In  medical procedures, especially haemodialysis
      (HD) and related therapies (haemodiafiltration (HDF), haemofiltration (HF)),
      endotoxins in the water for haemodialysis can permeate through the haemodialysis
      membrane and cause microinflammation or various haemodialysis-related illnesses.
      To decrease such a biological risk, RO and UF membranes are generally used. Also,
      hot water disinfection or the chemical disinfection is regularly executed to kill
      bacteria which produce endotoxins. However, simple treatment methods and
      equipment may be able to decrease the biological risk more efficiently. In our
      experiments, we confirmed that viable bacteria and endotoxins were removed by
      Electro Deionization (EDI) technology and also clarified the desorption
      mechanisms.

PMID- 21946322
TI  - Cell viability of four corneoconjunctival cell lines exposed to five
      preservatives and a surfactant used for infection control in eyedrops.
AB  - The aim of this study was to evaluate the cytotoxicity of six ingredients used in
      eyedrops with regard to four corneoconjunctival cell lines. Cells were treated
      with the undiluted solution, and 2-fold, and 10-fold dilutions of each solution
      for 10, 30, and 60 min and cell viability was measured with the neutral red assay
      and the MTT assay. The degree of toxicity was based on the cell viability score
      (CVS). The CVS50 was determined by the number of measurements with a viability >=
      50% of control. The CVS40/80 was calculated as follows: CVS40/80 = (number of
      measurements with a viability value >80%) - (number of measurements with a
      viability value <40%). Results were expressed as % of total measurements (%CVS).
      The results of each ingredient for %CVS50, and %CVS40/80 were 0.01% benzalkonium
      chloride (51, -13), 1% boric acid (100, 99), 0.4% methyl paraoxybenzoate (100,
      100), 0.4% propyl paraoxybenzoate (100, 100), 1.0% polysorbate 80 (68, 18), and
      0.5% chlorobutanol (100, 100). The use of benzalkonium chloride led to apparently
      low cell viability compared to the other five solutions.

PMID- 21946323
TI  - The mode of action of sodium hypochlorite in the decolorization of azo dye orange
      II in aqueous solution.
AB  - The effect of sodium hypochlorite (NaOCl) on the decolorization of azo dye orange
      II (4-[(2-hydroxy-1-naphthalenyl) azo]-benzenesulfonic acid, monosodium salt) in
      aqueous solution was studied as a function of pH. The first-order rate constant
      of color reduction (k) was evaluated from the curve of color reduction in the
      initial stage of decolorization. The k values increased with increasing the pH
      from 5.4 to 9.3 and the NaOCl concentration from 2.82 * 10(-4) M to 1.13 * 10(-3)
      M. It was found that k depended on the concentration of OCl(-), but not on HOCl.
      On the other hand, k decreased markedly at pHs more than 10, depending on pH.
      This suggested that the reactivity of the orange II molecule with OCl(-)
      decreased probably due to the competitive action of the hydroxide ion under
      alkaline conditions. It could be concluded that controlling the solution pH and
      the OCl(-) concentration was indeed a key factor determining the rate of
      decolorization of orange II in aqueous solution.

PMID- 21946324
TI  - Anti-tumor activity of CrTX in human lung adenocarcinoma cell line A549.
AB  - AIM: To assess the cytotoxic effect of crotoxin (CrTX), a potent neurotoxin
      extracted from the venom of the pit viper Crotalus durissus terrificus, in human
      lung adenocarcinoma A549 cells and investigated the underlying mechanisms.
      METHODS: A549 cells were treated with gradient concentrations of CrTX, and the
      cell cycle and apoptosis were analyzed using a flow cytometric assay. The changes
      of cellular effectors p53, caspase-3 and cleaved caspase-3, total P38MAPK and
      pP38MAPK were investigated using Western blot assays. A549 xenograft model was
      used to examine the inhibition of CrTX on tumor growth in vivo. RESULTS:
      Treatment of A549 cells with CrTX (25-200 MUg/mL) for 48 h significantly
      inhibited the cell growth in a dose-dependent manner (IC(50)=78 MUg/mL).
      Treatment with CrTX (25 MUg/mL) for 24 h caused G1 arrest and induced cell
      apoptosis. CrTX (25 MUg/mL) significantly increased the expression of wt p53,
      cleaved caspase-3 and phospho-P38MAPK. Pretreatment with the specific P38MAPK
      inhibitor SB203580 (5 MUmol/L) significantly reduced CrTX-induced apoptosis and
      cleaved caspase-3 level, but G(1) arrest remained unchanged and highly expressed
      p53 sustained. Intraperitoneal injection of CrTX (10 MUg/kg, twice a week for 4
      weeks) significantly inhibited A549 tumor xenograft growth, and decreased MVD and
      VEGF levels. CONCLUSION: CrTX produced significant anti-tumor effects by inducing
      cell apoptosis probably due to activation of P38MAPK and caspase-3, and by cell
      cycle arrest mediated by increased wt p53 expression. In addition, CrTX displayed
      anti-angiogenic effects in vivo.

PMID- 21946325
TI  - Subthalamic nucleus stimulation reverses mediofrontal influence over decision
      threshold.
AB  - It takes effort and time to tame one's impulses. Although medial prefrontal
      cortex (mPFC) is broadly implicated in effortful control over behavior, the
      subthalamic nucleus (STN) is specifically thought to contribute by acting as a
      brake on cortico-striatal function during decision conflict, buying time until
      the right decision can be made. Using the drift diffusion model of decision
      making, we found that trial-to-trial increases in mPFC activity (EEG theta power,
      4-8 Hz) were related to an increased threshold for evidence accumulation
      (decision threshold) as a function of conflict. Deep brain stimulation of the STN
      in individuals with Parkinson's disease reversed this relationship, resulting in
      impulsive choice. In addition, intracranial recordings of the STN area revealed
      increased activity (2.5-5 Hz) during these same high-conflict decisions. Activity
      in these slow frequency bands may reflect a neural substrate for cortico-basal
      ganglia communication regulating decision processes.

PMID- 21946326
TI  - Neural activity at the human olfactory epithelium reflects olfactory perception.
AB  - Organization of receptive surfaces reflects primary axes of perception. In
      vision, retinal coordinates reflect spatial coordinates. In audition, cochlear
      coordinates reflect tonal coordinates. However, the rules underlying the
      organization of the olfactory receptive surface are unknown. To test the
      hypothesis that organization of the olfactory epithelium reflects olfactory
      perception, we inserted an electrode into the human olfactory epithelium to
      directly measure odorant-induced evoked responses. We found that pairwise
      differences in odorant pleasantness predicted pairwise differences in response
      magnitude; that is, a location that responded maximally to a pleasant odorant was
      likely to respond strongly to other pleasant odorants, and a location that
      responded maximally to an unpleasant odorant was likely to respond strongly to
      other unpleasant odorants. Moreover, the extent of an individual's perceptual
      span predicted their span in evoked response. This suggests that, similarly to
      receptor surfaces for vision and audition, organization of the olfactory receptor
      surface reflects key axes of perception.

PMID- 21946327
TI  - Amygdala lesions selectively impair familiarity in recognition memory.
AB  - A major controversy in the study of memory concerns whether there are distinct
      medial temporal lobe (MTL) substrates of recollection and familiarity. Studies
      using receiver operating characteristics analyses of recognition memory indicate
      that the hippocampus is essential for recollection, but not for familiarity. We
      found the converse pattern in the amygdala, wherein damage impaired familiarity
      while sparing recollection. Combined with previous findings, these results
      dissociate recollection and familiarity by selective MTL damage.

PMID- 21946328
TI  - Hemisphere-specific optogenetic stimulation reveals left-right asymmetry of
      hippocampal plasticity.
AB  - Postsynaptic spines at CA3-CA1 synapses differ in glutamate receptor composition
      according to the hemispheric origin of CA3 afferents. To study the functional
      consequences of this asymmetry, we used optogenetic tools to selectively
      stimulate axons of CA3 pyramidal cells originating in either left or right mouse
      hippocampus. We found that left CA3 input produced more long-term potentiation at
      CA1 synapses than right CA3 input as a result of differential expression of
      GluN2B subunit-containing NMDA receptors.

PMID- 21946329
TI  - A DNA methylation microarray-based study identifies ERG as a gene commonly
      methylated in prostate cancer.
AB  - DNA methylation of promoter regions is a common event in prostate cancer, one of
      the most common cancers in men worldwide. Because prior reports demonstrating
      that DNA methylation is important in prostate cancer studied a limited number of
      genes, we systematically quantified the DNA methylation status of 1505 CpG
      dinucleotides for 807 genes in 78 paraffin-embedded prostate cancer samples and
      three normal prostate samples. The ERG gene, commonly repressed in prostate cells
      in the absence of an oncogenic fusion to the TMPRSS2 gene, was one of the most
      commonly methylated genes, occurring in 74% of prostate cancer specimens. In an
      independent group of patient samples, we confirmed that ERG DNA methylation was
      common, occurring in 57% of specimens, and cancer-specific. The ERG promoter is
      marked by repressive chromatin marks mediated by polycomb proteins in both normal
      prostate cells and prostate cancer cells, which may explain ERG's predisposition
      to DNA methylation and the fact that tumors with ERG DNA methylation were more
      methylated, in general. These results demonstrate that bead arrays offer a high
      throughput method to discover novel genes with promoter DNA methylation such as
      ERG, whose measurement may improve our ability to more accurately detect prostate
      cancer.

PMID- 21946330
TI  - Identification of a DNA methylome signature of esophageal squamous cell carcinoma
      and potential epigenetic biomarkers.
AB  - Esophageal squamous cell carcinoma (ESCC) is believed to arise from esophageal
      mucosa through accumulation of both genetic and epigenetic changes. DNA
      methylation is a critical epigenetic mechanism involved in key cellular processes
      and its deregulation has been linked to many human cancers, including ESCC. The
      aim of this study is to examine the global deregulation of methylation states in
      ESCC and identify potential early biomarkers. With this purpose, we performed a
      bead array analysis of more than 800 cancer-related genes in ten ESCC samples,
      ten matched surrounding tissues and four esophageal mucosa from healthy
      individuals. Pyrosequencing was used for validation of DNA methylation changes in
      up to 106 cases and 27 controls. A total of 37 CpG sites were found to be
      differentially methylated between tumors and surrounding tissues. These CpG sites
      were significantly enriched in genes related to several pathways including IL-10
      anti-inflammatory signaling pathway and cell communication pathway. In addition,
      by comparing with healthy esophageal mucosa, we identified TFF1 gene as a
      potential early marker of ESCC. This is the first study to address methylation
      changes in ESCC in a large set of genes. Methylome analysis is shown as a
      sensitive and powerful tool to identify molecular players in ESCC. These data
      should prove to be the reference for future studies identifying potential
      biomarkers and molecular targets in ESCC.

PMID- 21946331
TI  - In-vitro acetylcholine release is not a straightforward model to study
      hippocampal 5-HT4 receptors.
AB  - 5-HT4 receptor (5-HT4R) activation induces procognitive effects. This might be
      related to stimulation of hippocampal acetylcholine release, which has been shown
      for 5-HT4R agonists in in-vivo models. We investigated the influence of the 5
      HT4R agonists, prucalopride and BIMU-8, on acetylcholine release in rat
      hippocampal brain slices. In contrast to the report by Siniscalchi et al., no
      facilitating effect of 5-HT4R agonists on electrically evoked acetylcholine could
      be shown. The in our hands absence of an effect by 5-HT4R agonists illustrates
      that an in-vitro evaluation of 5-HT4R agonists on hippocampal acetylcholine
      release is not a straightforward model to study the relationship between
      hippocampal 5-HT4Rs and hippocampal acetylcholine release.

PMID- 21946332
TI  - Real-life experience modifies early electrophysiological responses in the visual
      system.
AB  - To examine whether experience can alter the sensitivity of the visual system to
      particular aspects of visual processing, 17 earthquake survivors and 17 controls
      were exposed to pictures of objects, and were required to identify the unbroken
      ones by checking for flaws on the surface. The electrophysiological results
      indicated that approximately 150 ms after presentation of a visual stimulus, the
      earthquake survivors showed an enhanced negativity (N1) as compared with the
      controls. This finding supports the claim that the pattern of neural activity
      associated with the early stages of object perception can be modified by real
      world experiences.

PMID- 21946333
TI  - Tactile interactions activate mirror system regions in the human brain.
AB  - Communicating with others is essential for the development of a society. Although
      types of communications, such as language and visual gestures, were thoroughly
      investigated in the past, little research has been done to investigate
      interactions through touch. To study this we used functional magnetic resonance
      imaging. Twelve participants were scanned with their eyes covered while stroking
      four kinds of items, representing different somatosensory stimuli: a human hand,
      a realistic rubber hand, an object, and a simple texture. Although the human and
      the rubber hands had the same overall shape, in three regions there was
      significantly more blood oxygen level dependent activation when touching the real
      hand: the anterior medial prefrontal cortex, the ventral premotor cortex, and the
      posterior superior temporal cortex. The last two regions are part of the mirror
      network and are known to be activated through visual interactions such as
      gestures. Interestingly, in this study, these areas were activated through a
      somatosensory interaction. A control experiment was performed to eliminate
      confounds of temperature, texture, and imagery, suggesting that the activation in
      these areas was correlated with the touch of a human hand. These results reveal
      the neuronal network working behind human tactile interactions, and highlight the
      participation of the mirror system in such functions.

PMID- 21946334
TI  - Microarray expression analysis in idiopathic and LRRK2-associated Parkinson's
      disease.
AB  - LRRK2 mutations are the most common genetic cause of Parkinson's disease (PD). We
      performed a whole-genome RNA profiling of putamen tissue from idiopathic PD
      (IPD), LRRK2-associated PD (G2019S mutation), neurologically healthy controls and
      one asymptomatic LRRK2 mutation carrier, by using the Genechip Human Exon 1.0-ST
      Array. The differentially expressed genes found in IPD revealed an alteration of
      biological pathways related to long-term potentiation (LTP), GABA receptor
      signalling, and calcium signalling pathways, among others. These pathways are
      mainly related with cell signalling cascades and synaptic plasticity processes.
      They were also altered in the asymptomatic LRRK2 mutation carrier but not in the
      LRRK2-associated PD group. The expression changes seen in IPD might be attributed
      to an adaptive consequence of a dysfunction in the dopamine transmission. The
      lack of these altered molecular pathways in LRRK2-associated PD patients suggests
      that these cases could show a different molecular response to dopamine
      transmission impairment.

PMID- 21946335
TI  - Age-dependent neurovascular abnormalities and altered microglial morphology in
      the YAC128 mouse model of Huntington disease.
AB  - Central nervous system (CNS) inflammatory processes including microglial
      activation have been implicated in the pathogenesis of neurodegenerative diseases
      such as Huntington Disease (HD). We report age-dependent changes in striatal
      microglial morphology and vasculature in the YAC128 mouse model of HD. Decreases
      in microglial ramification along with a decrease in vessel diameter and increased
      vessel density and length suggest the presence of microgliosis and proangiogenic
      activity in YAC128 mice. Our hypothesis for this study was that the changes in
      microglial morphology and perturbations in vasculature may be involved in the
      pathogenesis of HD and that peripheral challenge with the bacterial endotoxin,
      lipopolysaccharide (LPS), will exacerbate these microglial and vascular changes
      as well as the HD phenotype in YAC128 mice at 12 months. Chronic peripheral LPS
      (1mg/kg) potentiated microglial activation indicated by an increase in microglial
      cell body size and retraction of processes. This potentiation in microglial
      activation with chronic peripheral LPS challenge was paralleled with vascular
      remodeling including dilatation, increased vessel wall thickness, increased BBB
      permeability and fibrinogen deposition in YAC128 striatum. Although peripheral
      LPS caused an increase in microglial activation and degenerative changes in
      cerebrovasculature, the phenotypic hallmarks of HD in YAC128 mice such as motor
      coordination deficits and decreased striatal volume were not exacerbated by
      chronic peripheral LPS exposure. This study identifies age-dependent increases in
      microglial activation and angiogenesis in YAC128 at 12 months. Peripheral
      inflammation induced by chronic LPS causes similar changes but does not influence
      the HD phenotype in YAC128 mice.

PMID- 21946336
TI  - Rapid and simple identification of human pathogenic heterophyid intestinal fluke
      metacercariae by PCR-RFLP.
AB  - Six species of heterophyid intestinal flukes (HIFs) constitute the major endemic
      zoonotic fish-borne pathogens in Asia: Haplorchis taichui, H. pumilio, H.
      yokogawai, Procerovum varium, Stellantchasmus falcatus, and Centrocestus
      formosanus. Several different species of these parasites are often found co
      infecting the same second intermediate fish host. Because of their morphological
      similarities, differentiating between species of HIF metacercariae is difficult,
      time-consuming, and frequently results in misidentification. In this study, we
      aimed to develop an efficient and accurate method of identifying metacercariae of
      these 6 HIFs. Metacercariae were roughly grouped together, based on morphological
      characteristics seen under a stereomicroscope. Then, PCR-restriction fragment
      length polymorphism (PCR-RFLP) was used to identify the exact species of each
      metacercaria, using the 28S ribosomal RNA gene as the genetic marker and MboII as
      the restriction enzyme. Using a combination of morphological and molecular
      methods eliminates the need for DNA sequencing and infecting animal subjects to
      obtain adult worms, increases accuracy, and decreases the need for laborious
      morphological identification. Because the method is simple, rapid, and relatively
      cheap compared with PCR-sequencing, it may be an effective tool for
      epidemiological studies of HIFs in endemic areas.

PMID- 21946337
TI  - Human paragonimiasis in Viet Nam: epidemiological survey and identification of
      the responsible species by DNA sequencing of eggs in patients' sputum.
AB  - Parasitological and sero-epidemiological surveys for human paragonimiasis were
      conducted in three provinces of Viet Nam. A total of 590 participants from two
      known endemic areas of human paragonimiasis (Sinho district of Laichau province
      and Lucyen district of Yenbai province) and from Dakrong district of Quangtri
      province where we recently found crab hosts heavily infected with Paragonimus
      westermani metacercariae. By multiple dot-ELISA screening, 28 (12.7%) out of 220
      participants in Sinho district of Laichau province and 4 (3.3%) out of 120
      participants in Lucyen district of Yenbai province were proven to be antibody
      positive against the Paragonimus antigen. None of the 250 sera of the residents
      in Dakrong, Quangtri province, gave sero-positivity. Among a total of 32 sero
      positive patients Paragonimus eggs were found in 6 cases. ITS2 sequences were
      successfully determined from a single Paragonimus egg from each patient. The
      results of homology search by BLAST and alignment clearly confirmed that
      Paragonimus eggs collected from 6 patients were all of Paragonimus heterotremus.
      The pathogenicity of P. westermani for human paragonimiasis in Viet Nam is still
      questionable and needs to be explored in the future.

PMID- 21946338
TI  - Syncope triggered by a premature ventricular complex: a case of atrial
      fibrillation and paroxysmal atrioventricular block.

PMID- 21946339
TI  - Long-RP supraventricular tachycardia with 1:1 AV relationship: what is the
      mechanism?

PMID- 21946340
TI  - Orbits and implants: trends in indications, utilization, and complications in
      pediatric device therapy.

PMID- 21946341
TI  - Is there a relationship between complex fractionated atrial electrograms recorded
      during atrial fibrillation and sinus rhythm fractionation?
AB  - BACKGROUND: Ablation of persistent atrial fibrillation (AF) may require
      adjunctive methods of substrate modification. Both ablation-targeting complex
      fractionated atrial electrograms (CFAEs) recorded during AF and fractionated
      electrograms recorded during sinus rhythm (sinus rhythm fractionation [SRF]) have
      been described. However, the relationship of CFAEs with SRF is unclear. METHODS:
      Twenty patients (age 62 +/- 9 years, 13 males) with persistent AF and 9 control
      subjects without organic heart disease or AF (age 36 +/- 6 years, 4 males)
      underwent detailed CFAE and SRF left atrial electroanatomic maps. The overlap in
      left atrial regions with CFAEs and SRF was compared in the AF population, and the
      distribution of SRF was compared among patients with AF and normal controls.
      Propagation maps were analyzed to identify the activation patterns associated
      with SR fractionation. RESULTS: SRF (338 +/- 150 points) and CFAE (418 +/- 135
      points) regions comprised 29% +/- 14% and 25% +/- 15% of the left atrial surface
      area, respectively. There was no significant correlation between SRF and CFAE
      maps (r = .2; P = NS). On comparing patients with AF and controls, no significant
      difference was found in the distribution of SRF between groups (P = .74). Regions
      of SRF overlapped areas of wave-front collision 75% +/- 13% of the time.
      CONCLUSIONS: (1) There is little overlap between regions of CFAEs during AF and
      regions of SRF measured in the time domain or the frequency domain, (2) the
      majority of SRF appears to occur in regions with wave-front collision, (3) the
      distribution of SRF is similar in patients with AF and normal controls,
      suggesting that this may not have an important role in AF maintenance and may not
      be a suitable ablation target.

PMID- 21946342
TI  - Parental influence on child change in physical activity during a family-based
      intervention for child weight gain prevention.
AB  - BACKGROUND: This study examined the association between parent and child change
      in physical activity during a family-based intervention for child weight gain
      prevention. METHODS: Daily step counts were recorded for parents and children in
      83 families given a goal to increase activity by 2000 steps per day above
      baseline. Linear mixed effects models were used to predict child change in daily
      step counts from parental change in step counts. RESULTS: Both maternal (P <
      .0001) and paternal (P < .0001) change in step counts for the current day
      strongly predicted child change in step counts for that day. On average, a child
      took an additional 2117.6 steps above baseline on days his or her mother met her
      goal versus 1175.2 additional steps when the mother did not meet her goal. The
      respective values were 1598.0 versus 1123.1 steps for fathers. Day of week
      moderated the maternal effect (P = .0019), with a larger impact on Saturday and
      Sunday compared with weekdays. A similar but nonsignificant pattern was observed
      for fathers. CONCLUSIONS: Encouraging parents to increase physical activity,
      particularly on weekends, may be a highly effective way to leverage parental
      involvement in interventions to increase children's physical activity.

PMID- 21946344
TI  - The spatiotemporal characteristics of elementary audiovisual speech and music
      processing in musically untrained subjects.
AB  - Previously, the EEG technique has been used to investigate the spatiotemporal
      properties of audiovisual (AV) processing by taking advantage of the violation of
      the "additive model", which is considered to be a very conservative approach. In
      the present work, we used a less conservative and novel approach than the
      criterion of superadditivity for estimating AV interactions. Hence, we estimated
      AV interaction patterns by comparing the responses to AV stimuli with the
      averaged responses to the unimodal visual and auditory stimuli in musically
      untrained subjects and by presenting syllables and piano tones coupled with
      flashlights. Our results suggest that the two AV objects elicited consistent
      interaction patterns within the time course of unisensory processing in the time
      range between 80 and 250ms post stimulus onset. The scalp topographies, as well
      as the source estimation approach we adopted, indicate that the first interaction
      pattern at around 100ms was partially driven by auditory-related cortical
      regions. Additionally, we found evidence for a second interaction pattern at
      around 200ms that was mainly associated with the responsiveness of extra-sensory
      brain regions. During this later processing stage, only the music condition was
      associated with putative responses that originated from auditory-related cortical
      fields. This study provides a novel approach to investigate the basic principles
      underlying elementary AV speech and music processing in subjects without formal
      musical education.

PMID- 21946343
TI  - Does antiepileptogenesis affect sleep in genetic epileptic rats?
AB  - Recently it was established that early long lasting treatment with the anti
      absence drug ethosuximide (ETX) delays the occurrence of absences and reduces
      depressive-like symptoms in a genetic model for absence epilepsy, rats of the
      WAG/Rij strain. Here it is investigated whether anti-epileptogenesis (chronic
      treatments with ETX for 2 and 4 months) affects REM sleep in this model. Four
      groups of weaned male WAG/Rij rats were treated with ETX for 4 months, two groups
      for 2 months (at 2-3 and 4-5 months of age), the fourth group was untreated.
      Next, the rats were recorded 6 days after the last day of the treatment for 22.5
      h. Non-REM sleep and REM sleep parameters and delta power were analyzed in four
      characteristic and representative hours of the recoding period. Four months
      treatment with ETX reduced the amount of REM sleep and REM sleep as percentage of
      total sleep time. Other sleep parameters were not affected by the treatment.
      Clear differences between the various hours of the light-dark phase in amounts of
      non-REM and REM sleep and delta power were found, in line with commonly reported
      circadian sleep patterns. It can be concluded that the reduction of REM sleep is
      unique for the early and long lasting chronic treatment. The outcomes may explain
      our earlier finding that a reduction of REM sleep might alleviate depressive like
      symptoms.

PMID- 21946345
TI  - Dysmorphology in the era of whole exome sequencing.

PMID- 21946346
TI  - Enzyme replacement therapy for lysosomal storage diseases.
AB  - PURPOSE OF REVIEW: Enzyme replacement therapy (ERT) for type 1 Gaucher has been
      highly successful. ERT is now available for other lysosomal storage disorders
      (LSDs) but none of these highly expensive treatments has had the same efficacy.
      This review explores why these newer treatments have failed to live up to
      expectations and how future products might be made more effective. RECENT
      FINDINGS: In Gaucher, the target cells for ERT are macrophages, which are
      efficiently accessed by intravenously injected recombinant enzyme. The target
      tissues in other LSDs receive much lower doses of enzyme and intravenous ERT does
      not enter the brain at all. Uptake of recombinant enzyme is via the mannose-6
      phosphate receptor (M6PR). Recent work has looked at improving the efficiency of
      enzyme delivery to tissues by altering both the ligand on the infused enzyme and
      the expression of the M6PR on cells. For delivery to the central nervous system,
      intrathecal routes of administration have been explored. SUMMARY: Work in tissue
      culture and in animal models has shown increased efficiency of enzyme delivery
      and clinical trials of second-generation products and novel delivery systems are
      now underway.

PMID- 21946347
TI  - An unorthodox pancreatic lesion in a young man presenting with jaundice.

PMID- 21946348
TI  - Effect of neonatal nutrition on long-term barrier function and gut inflammation.

PMID- 21946349
TI  - A rare complication of endoscopic cystgastrostomy.

PMID- 21946352
TI  - Exon capture analysis of G protein-coupled receptors identifies activating
      mutations in GRM3 in melanoma.
AB  - G protein-coupled receptors (GPCRs), the largest human gene family, are important
      regulators of signaling pathways. However, knowledge of their genetic alterations
      is limited. In this study, we used exon capture and massively parallel sequencing
      methods to analyze the mutational status of 734 GPCRs in melanoma. This
      investigation revealed that one family member, GRM3, was frequently mutated and
      that one of its mutations clustered within one position. Biochemical analysis of
      GRM3 alterations revealed that mutant GRM3 selectively regulated the
      phosphorylation of MEK, leading to increased anchorage-independent growth and
      migration. Melanoma cells expressing mutant GRM3 had reduced cell growth and
      cellular migration after short hairpin RNA-mediated knockdown of GRM3 or
      treatment with a selective MEK inhibitor, AZD-6244, which is currently being used
      in phase 2 clinical trials. Our study yields the most comprehensive map of
      genetic alterations in the GPCR gene family.

PMID- 21946351
TI  - A germline variant in the TP53 polyadenylation signal confers cancer
      susceptibility.
AB  - To identify new risk variants for cutaneous basal cell carcinoma, we performed a
      genome-wide association study of 16 million SNPs identified through whole-genome
      sequencing of 457 Icelanders. We imputed genotypes for 41,675 Illumina SNP chip
      typed Icelanders and their relatives. In the discovery phase, the strongest
      signal came from rs78378222[C] (odds ratio (OR) = 2.36, P = 5.2 * 10(-17)), which
      has a frequency of 0.0192 in the Icelandic population. We then confirmed this
      association in non-Icelandic samples (OR = 1.75, P = 0.0060; overall OR = 2.16, P
      = 2.2 * 10(-20)). rs78378222 is in the 3' untranslated region of TP53 and changes
      the AATAAA polyadenylation signal to AATACA, resulting in impaired 3'-end
      processing of TP53 mRNA. Investigation of other tumor types identified
      associations of this SNP with prostate cancer (OR = 1.44, P = 2.4 * 10(-6)),
      glioma (OR = 2.35, P = 1.0 * 10(-5)) and colorectal adenoma (OR = 1.39, P = 1.6 *
      10(-4)). However, we observed no effect for breast cancer, a common Li-Fraumeni
      syndrome tumor (OR = 1.06, P = 0.57, 95% confidence interval 0.88-1.27).

PMID- 21946354
TI  - Identification of a functional transposon insertion in the maize domestication
      gene tb1.
AB  - Genetic diversity created by transposable elements is an important source of
      functional variation upon which selection acts during evolution. Transposable
      elements are associated with adaptation to temperate climates in Drosophila, a
      SINE element is associated with the domestication of small dog breeds from the
      gray wolf and there is evidence that transposable elements were targets of
      selection during human evolution. Although the list of examples of transposable
      elements associated with host gene function continues to grow, proof that
      transposable elements are causative and not just correlated with functional
      variation is limited. Here we show that a transposable element (Hopscotch)
      inserted in a regulatory region of the maize domestication gene, teosinte
      branched1 (tb1), acts as an enhancer of gene expression and partially explains
      the increased apical dominance in maize compared to its progenitor, teosinte.
      Molecular dating indicates that the Hopscotch insertion predates maize
      domestication by at least 10,000 years, indicating that selection acted on
      standing variation rather than new mutation.

PMID- 21946353
TI  - Transposon-mediated rewiring of gene regulatory networks contributed to the
      evolution of pregnancy in mammals.
AB  - A fundamental challenge in biology is explaining the origin of novel phenotypic
      characters such as new cell types; the molecular mechanisms that give rise to
      novelties are unclear. We explored the gene regulatory landscape of mammalian
      endometrial cells using comparative RNA-Seq and found that 1,532 genes were
      recruited into endometrial expression in placental mammals, indicating that the
      evolution of pregnancy was associated with a large-scale rewiring of the gene
      regulatory network. About 13% of recruited genes are within 200 kb of a Eutherian
      specific transposable element (MER20). These transposons have the epigenetic
      signatures of enhancers, insulators and repressors, directly bind transcription
      factors essential for pregnancy and coordinately regulate gene expression in
      response to progesterone and cAMP. We conclude that the transposable element,
      MER20, contributed to the origin of a novel gene regulatory network dedicated to
      pregnancy in placental mammals, particularly by recruiting the cAMP signaling
      pathway into endometrial stromal cells.

PMID- 21946355
TI  - Gender differences in age-related changes in left and right ventricular
      geometries and functions. Echocardiography of a healthy subject group.
AB  - BACKGROUND: The purpose of the present study was to investigate gender
      differences in age-related changes of left ventricular (LV) and right ventricular
      (RV) geometries and functions throughout the entire adult age range using the
      Japanese Normal Values for Echocardiographic Measurements Project (JAMP) study
      database. METHODS AND RESULTS: Seven hundred healthy volunteers (aged 20-79
      years) underwent 2-dimensional and Doppler echocardiography. The subjects were
      stratified into 6 different age groups and then stratified by gender in each age
      group. LV diastolic function was assessed from pulsed wave Doppler measurements
      of mitral early (E) and late (A) inflow velocities and tissue Doppler
      measurements of mitral early (e') and late (a') annular velocities. LV volume
      decreased and LV mass increased with age to a similar extent in both men and
      women. Furthermore, for subjects <50 years, women had significantly greater E,
      E/A ratio and e' than men, but these parameters were similar between genders in
      subjects >50 years. In addition, there was a significant interaction between age
      and gender that affected the differences in E, e' and E/e' among the groups
      (P<0.03, P<0.01, and P<0.03, respectively; ANOVA). There were no gender
      differences in age-related changes in RV parameters. CONCLUSIONS: Gender
      differences were found in age-related changes in LV diastolic function in a
      healthy population. Gender differences should be considered for optimal diagnosis
      and management of cardiovascular disease.

PMID- 21946356
TI  - Breakdown of the intermediate-term fractal scaling exponent in sinus node
      dysfunction. New method for non-invasive evaluation of sinus node function.
AB  - BACKGROUND: The aim of the present study was to characterize the heart rate
      dynamics of sinus bradycardia (SB) from sinus node dysfunction (SND) using non
      linear dynamical system analysis. No data are yet available on how the dynamics
      change in the presence of SND. METHODS AND RESULTS: Conventional time and
      frequency domain analysis, the short- (DFAalpha(1)) and intermediate-term fractal
      scaling exponent (DFAalpha(2)), approximate entropy (ApEn) and sample entropy
      (SampEn) were calculated in 60-min sinus RR interval data of SB from 24-h
      ambulatory electrocardiograms of 110 patients: 44 SND patients, 44 age-matched
      controls, and 22 younger controls. All of the time and frequency domain
      parameters, ApEn and SampEn, were significantly reduced in the age-matched
      control group, compared with the young control group. DFAalpha(1) and DFAalpha(2)
      increased with aging. Both the DFAalpha(1) and DFAalpha(2) of SND patients were
      paradoxically reduced, which was not appropriate for their age. Only the
      percentage of consecutive RR intervals with absolute differences >50ms (pNN(50)),
      low-frequency power, and DFAalpha(2) made a significant contribution to
      prediction of SND on logistic regression analysis. Among them, DFAalpha(2) was
      the most significant variable for prediction of SND (odds ratio, 0.927; 95%
      confidence interval: 0.888-0.969, P=0.001). DFAalpha(2) remained as a significant
      variable for prediction of SND, when compared with overall control patients,
      combining the 2 control groups. CONCLUSIONS: Inappropriate reduction of
      DFAalpha(2) is a robust measure and could be an adjunctive tool for improvement
      of diagnostic performance in detection of SND.

PMID- 21946350
TI  - Genome-wide association and large-scale follow up identifies 16 new loci
      influencing lung function.
AB  - Pulmonary function measures reflect respiratory health and are used in the
      diagnosis of chronic obstructive pulmonary disease. We tested genome-wide
      association with forced expiratory volume in 1 second and the ratio of forced
      expiratory volume in 1 second to forced vital capacity in 48,201 individuals of
      European ancestry with follow up of the top associations in up to an additional
      46,411 individuals. We identified new regions showing association (combined P < 5
      * 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM
      (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1,
      CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide
      insight into the molecular mechanisms regulating pulmonary function and into
      molecular targets for future therapy to alleviate reduced lung function.

PMID- 21946357
TI  - Relationship between microalbuminuria and vulnerable plaque components in
      patients with acute coronary syndrome and with diabetes mellitus. Virtual
      histology-intravascular ultrasound.
AB  - BACKGROUND: The purpose of the present study was to use virtual histology
      intravascular ultrasound (VH-IVUS) to evaluate the relationship between
      microalbuminuria and plaque components in 920 patients. METHODS AND RESULTS:
      Patients with albumin levels <30mg/g creatinine were defined as having
      normoalbuminuria (n=824), and those with albumin levels 30-300mg/g as having
      microalbuminuria (n=96). The microalbuminuria group contained more patients with
      acute coronary syndrome (ACS; 72% vs. 61%, P=0.018) and more patients with
      diabetes (53% vs. 26%, P<0.001). In ACS patients, %necrotic core (NC) volume was
      significantly greater in the microalbuminuria group compared with the
      normoalbuminuria group (19+/-10% vs. 15+/-9%, P=0.019), but not in patients with
      stable angina. In ACS patients, thin-cap fibroatheroma (TCFA) was observed more
      frequently in the microalbuminuria group (36% vs. 18%, P=0.008), and
      microalbuminuria was the independent predictor of TCFA (odds ratio [OR], 1.106;
      95% confidence interval [CI]: 1.025-1.144, P=0.018). In diabetic patients, %NC
      volume was significantly greater in the microalbuminuria group compared with the
      normoalbuminuria group (20+/-9% vs. 16+/-10%, P=0.017), but not in non-diabetic
      patients. In diabetic patients, TCFA was observed more frequently in the
      microalbuminuria group (38% vs. 17%, P=0.002) and microalbuminuria was the
      independent predictor of TCFA (OR, 1.120; 95%CI: 1.038-1.204, P=0.012).
      CONCLUSIONS: Microalbuminuria was associated with a higher number of vulnerable
      plaque components in ACS and diabetic patients. More intensive medical therapy is
      needed to stabilize the vulnerable plaque if microalbuminuria is observed in
      diabetic ACS patients.

PMID- 21946358
TI  - Progression of isolated tricuspid regurgitation late after left-sided valve
      surgery. Clinical features and mechanisms.
AB  - BACKGROUND: Severe tricuspid regurgitation (TR) sometimes develops late after
      left-sided valve surgery without left heart failure, pulmonary hypertension or
      rheumatic tricuspid valve. The purpose of the present study was to investigate
      clinical characteristics and mechanisms of severe isolated TR late after left
      sided valve surgery. METHODS AND RESULTS: A total of 372 consecutive patients who
      underwent left-sided valve surgery between 1990 and 2003 and who were followed up
      with echocardiography for at least 5 years, were retrospectively investigated.
      The mean follow-up period was 9.4 years. Clinical background, preoperative and
      postoperative echocardiographic parameters were evaluated. Among the 372
      patients, severe isolated TR was detected in 23 patients, which developed at a
      mean of 8.6 years after surgery. Twenty-two of 23 patients had undergone mitral
      valve surgery. Multivariate logistic regression analysis identified the presence
      of preoperative atrial fibrillation and preoperative ejection fraction as
      independent determinants for the development of severe isolated TR. In patients
      with severe isolated TR, the tricuspid annular diameter and the right atrial area
      were already enlarged early after surgery and both of these increased prior to TR
      progression. CONCLUSIONS: Severe isolated TR developing late after mitral valve
      surgery is not uncommon, thus it is important to recognize this disease entity.
      Annular dilatation was the main cause of isolated TR and serial echocardiographic
      data are important to detect progression of isolated TR and to assess its
      mechanisms.

PMID- 21946359
TI  - Functional communication within a perceptual network processing letters and
      pseudoletters.
AB  - Many studies have identified regions within human ventral visual stream to be
      important for object identification and categorization; however, knowledge of how
      perceptual information is communicated within the visual network is still
      limited. Current theories posit that if a high correspondence between incoming
      sensory information and internal representations exists, then the object is
      rapidly identified, and if there is not, then the object requires extra detailed
      processing. Event-related responses from the present magnetoencephalography study
      showed two main effects. The N1m peak latencies were approximately 15
      milliseconds earlier to familiar letters than to unfamiliar pseudoletters, and
      the N2m was more negative to pseudoletters than to letters. Event-related
      beamforming analyses identified these effects to be within bilateral visual
      cortices with a right lateralization for the N2m effect. Furthermore, functional
      connectivity analyses revealed that gamma-band (50-80 Hz) oscillatory phase
      synchronizations among occipital regions were greater to letters than to
      pseudoletters (around 85 milliseconds). However, during a later time interval
      between 245 and 375 milliseconds, pseudoletters elicited greater gamma-band phase
      synchronizations among a more distributed occipital network than did letters.
      These findings indicate that familiar object processing begins by at least 85
      milliseconds, which could represent an initial match to an internal template. In
      addition, unfamiliar object processing persisted longer than that for familiar
      objects, which could reflect greater attention to inexperienced objects to
      determine their identity and/or to consolidate a new template to aid in future
      identification.

PMID- 21946360
TI  - Clinical and EEG features of seizures in adults with down syndrome.
AB  - In this study, the authors characterized the clinical and EEG features of adult
      patients with Down syndrome who were referred, for more than a 10-year period, to
      the Epilepsy Clinic in the Cork University Hospital. A retrospective audit of the
      charts of 28 patients with Down syndrome who had an EEG performed in the Cork
      University Hospital between January 1, 2000, and September 30, 2009, including
      clinical follow-up, was carried out. Demographics, age at first seizure, seizure
      types, EEG findings, antiepileptic drugs, psychoactive medications, and seizure
      control were documented. Seizures most commonly began in the fourth decade of
      life. Generalized tonic-clonic seizures were the most common type of seizures (15
      patients, 54%), followed by complex partial seizures (5 patients, 18%) and
      generalized myoclonus (4 patients, 15%). A number of patients had more than one
      type of seizure. Diffuse background slowing was the dominant EEG abnormality seen
      in 17 patients (60%). Epileptiform activity was present in 5 patients (18%): 2
      had focal epileptiform discharges in the frontal regions, 1 in the central
      region, 1 in the central posterior region bilaterally, and 1 in the temporal
      regions. The six patients who had poor seizure control were those who had seizure
      onset from the fourth decade onward and clinically had complex partial seizures
      in combination with either generalized tonic-clonic or generalized myoclonus;
      four of them had epileptiform activity on EEG, with two having focal frontal
      epileptiform discharges: one in the central posterior areas bilaterally and one
      in the temporal regions. Five of the 28 patients had a normal EEG and 3 of these
      had a seizure disorder. There was no correlation found between use of
      psychoactive drugs and increased frequency/poor seizure control in patients in
      our study. This study documents the variability of clinical and
      electrophysiologic features in a well-characterized cohort of patients with Down
      syndrome with adult-onset epilepsy.

PMID- 21946361
TI  - The antidepressant treatment response index and treatment outcomes in a placebo
      controlled trial of fluoxetine.
AB  - Recent research aims at developing a biomarker to predict antidepressant
      treatment outcomes in major depressive disorder. The Antidepressant Treatment
      Response (ATR) index has been correlated with response to antidepressant
      medication (, ) but has not been assessed in a placebo-controlled trial. EEGs
      recorded at pretreatment baseline and after 1 week of randomized treatment were
      used to calculate ATR index for 23 subjects with major depressive disorder who
      were treated for 8 weeks with fluoxetine (FLX) 20 mg (n = 12) or placebo (n =
      11). The 17-item Hamilton Depression Rating Scale (HamD17) assessed symptom
      severity; ATR index was assessed as a predictor of percent change in HamD17
      score, endpoint response (>= 50% improvement) and remission (HamD17 score <= 7).
      The ATR index was significantly associated with improvement on FLX (r = 0.64, P =
      0.01), with a higher mean ATR index for FLX responders than for nonresponders
      (t(10) = -2.07, P = 0.03). Receiver operating characteristic analysis found a
      0.83 area under the curve (P = 0.03), for ATR index as a predictor for FLX, while
      an optimized ATR index cutoff of 47.3 yielded 100% sensitivity, 66.7%
      specificity, 75% positive predictive value, and 100% negative predictive value.
      Importantly, ATR index did not correlate significantly with placebo outcomes.
      Results extend ATR index findings to include predictive validity with fluoxetine,
      suggesting that this biomarker has specificity for drug effects.

PMID- 21946362
TI  - Outcome from therapeutic hypothermia and EEG.
AB  - PURPOSE: The aim of this study is to characterize the significance of EEG
      findings during therapeutic hypothermia. METHODS: The authors retrospectively
      reviewed continuous EEG monitoring data of every patient treated with therapeutic
      hypothermia after cardiac arrest from January 2008 to December 2009. EEG data
      were correlated with a functional outcome at the time of discharge. RESULTS: Data
      from 26 patients (14 men and 12 women) were reviewed. All the patients were
      treated with therapeutic hypothermia. The mean age was 60.3 years. The initial
      EEG background was severely depressed in 13 patients, suppression-burst pattern
      was present in 4 patients, alpha or theta coma pattern was present in 2 patients,
      generalized slow-wave activity was present in 3 patients, and generalized
      periodic epileptiform discharges were present in 4 patients. Epileptiform
      activity was present in 10 patients (38.5%). Initial background activity with
      generalized slow-wave activity correlated with better prognosis compared with
      other types of background activity (P = 0.017). CONCLUSIONS: The majority of
      patients (20 of 26) had poor outcomes despite therapeutic hypothermia. Continuous
      EEG background with generalized slow-wave activity correlated with survival and
      better prognosis in this study.

PMID- 21946363
TI  - SPECT-negative SIRPIDs argues against treatment as seizures.
AB  - Stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs) are a recently
      described form of epileptiform periodic discharges evoked by arousal. Similar to
      other periodic discharges (e.g., pseudoperiodic lateralized epileptiform
      discharges, generalized periodic epileptiform discharges, bilaterally independent
      epileptiform discharges), SIRPIDs lie somewhere along an ictal-interictal
      continuum. To determine whether SIRPIDs represent an ictal phenomenon reflected
      by increased focal cerebral perfusion on single-photon emission computerized
      tomography, or conversely an interictal pattern, the authors tested a patient
      with nonconvulsive status confirmed on EEG, which evolved to SIRPIDs with a
      concomittant contralateral hemiparesis. To test the ictal-increased flow
      hypothesis, a single-photon emission computerized tomography scan was obtained
      during a stimulus-induced train of rhythmic discharges on EEG, but it revealed no
      increase in tracer uptake. The authors conclude that SIRPIDs did not increase
      regional cerebral blood flow as would seizures. Thus, the evidence indicates
      little if any metabolic/blood flow activation with SIRPIDs, thus tempering the
      intensity with which SIRPIDs might be managed. This provides a testable paradigm
      for future patterns of uncertain epileptic significance.

PMID- 21946364
TI  - Asymmetric scalp electromyogram:  a common and accurate lateralizing sign in
      motor seizures.
AB  - PURPOSE: The early phase of motor seizures in focal epilepsy produces asymmetry
      of scalp electromyogram (ASEMG), observable as right-left inequality in muscle
      artifact on EEG. ASEMG is concordant with clinical lateralization when the
      seizure has clearly unilateral motor features (tonic, clonic, or versive
      movements), with higher electromyogram contralateral to the hemisphere of seizure
      onset. The authors explored whether ASEMG was also present in motor seizures
      without visible lateralizing signs. METHODS: Seizure classification by video
      telemetry data in a group of 106 focal epilepsy patients by semiology and ictal
      EEG. Assessment of ASEMG laterality by two reviewers. Computation of the kappa
      index of interobserver reliability. Calculation of the sensitivity and positive
      predictive value of ASEMG in motor seizures with regard to the laterality of the
      epileptogenic zone. RESULTS: Forty-eight of 106 patients had at least 1 motor
      seizure recorded. Of the total of 257 seizures recorded in the former, 174 (~68%)
      had a motor component. Forty such seizures had no clinical or EEG lateralization;
      ASEMG was, however, identified and accurate in 39 (97.5%). Generally, ASEMG was
      identified in 158 (90.8%) of all motor seizures, correctly lateralizing 156
      (89.6%). The next most common lateralizing sign was unilateral tonic, clonic, or
      dystonic posturing (44.8%). CONCLUSIONS: ASEMG is an accurate lateralizing sign,
      useful in seizures that have no alternative clinical lateralizing signs or ictal
      EEG lateralization. ASEMG was present in >90% of all motor seizures in this
      series, with a positive predictive value of 156 (>98%) of 158.

PMID- 21946365
TI  - Time-frequency analysis of somatosensory evoked potentials for intraoperative
      spinal cord monitoring.
AB  - PURPOSE: To evaluate the potential use of time-frequency analysis and its
      reliability in intraoperative somatosensory evoked potential (SEP) monitoring.
      METHODS: One hundred ninety-one patients undergoing thoracic and/or lumbar spinal
      surgery were studied retrospectively. The SEP signals were recorded during
      different stages of surgery. Averaged SEP was analyzed by short-time Fourier
      transform. The main peak in the time-frequency interpretation of SEP was measured
      in peak power, peak time, and peak frequency. The variability of these parameters
      was compared with that of amplitude and latency during different stages of
      surgery. The reliability of these parameters was also compared in true-positive
      and false-positive cases. RESULTS: During different surgical stages for the
      posterior tibial nerve SEP, the intrasubject variability of peak power was found
      to be more stable than that of amplitude, while the intrasubject variability of
      peak time did not show any difference compared with that of latency. The peak
      frequency presented stable during surgery. Moreover, the true-positive SEP case
      showed that peak power may detect the potential injury earlier than amplitude
      does. The false-positive outcomes could be reduced by the proposed method.
      CONCLUSIONS: The SEP peak component was found stable and reliable during the
      different stages of surgery. For clinical application purpose, time-frequency
      analysis was suggested to be an additional monitoring method besides the
      conventional amplitude/latency measurement since it provided a more reproducible
      and prompt response to the potential injury in intraoperative SEP monitoring.

PMID- 21946366
TI  - Carpal tunnel syndrome and ulnar neuropathy at the wrist:  comorbid disease or
      not?
AB  - The aim of this study was to elucidate the possible association between carpal
      tunnel syndrome (CTS) and ulnar neuropathy at the wrist because of the
      contradictory results of previous studies. Thus, a retrospective case-control
      study was arranged with an electromyographic database including patients between
      2003 and 2009. Patients were selected according to initial diagnosis and the
      examiner's criteria, and data were plotted by computer. One thousand nine hundred
      twenty-four patients were evaluated for CTS and 1,024 patients for diabetic CTS
      or diabetic polyneuropathy. CTS and ulnar neuropathy co-occurrence and CTS alone
      at the wrist was found in 54/404, 19/50, 20/27 patients, respectively. Logistic
      regression analysis revealed that having CTS was associated with a doubled risk
      of ulnar neuropathy at the wrist in both idiopathic CTS and diabetic CTS groups
      but not in diabetic polyneuropathy. Being male and of advanced age were other
      risk factors for ulnar neuropathy at the wrist. Correlation analysis (age and sex
      were controlled) revealed decreased but significant correlations between median
      and ulnar sensory amplitudes in CTS cases in all groups.

PMID- 21946367
TI  - Spectral power of 1-4 Hz frequency in the ictal phase of childhood absence
      epilepsy.
AB  - The ictal EEG of childhood absence epilepsy is characterized by short duration
      bursts of generalized 3-Hz spike-wave discharges, which are widely considered to
      be symmetric and synchronous. The purpose of this study was to investigate this
      assertion by studying the topography and spectral power of these discharges. The
      sample consisted of 7 subjects aged 4 to 9 years who had been diagnosed with
      childhood absence epilepsy by video-EEG monitoring. Computational EEG analysis
      was performed focusing on the slow-wave (1-4 Hz) component of the ictal EEG. We
      compared the spectral power of this slow-wave component in three brain regions
      (frontocentral, centroparietal, and parieto-occipital) and contrasted the
      spectral power of left and right fronto-central areas. Although five of seven
      subjects showed marked frontal dominance of spectral slow-wave power, two
      subjects had a different pattern characterized by a more diffuse anterior
      posterior distribution. Three patterns of spectral power laterality in the
      frontocentral region were observed: left dominant, equivocal, and right dominant.
      Each subject demonstrated the same pattern throughout his or her seizures (three
      to five ictal events) during video-EEG monitoring. These findings suggest that
      computational EEG may be useful for discerning subtle differences in the
      distribution of ictal waveforms. These observations also bolster the new ILAE
      definition of generalized seizures, suggesting that some so-called generalized
      seizures are not truly generalized but that they instead rapidly engage
      bilaterally distributed networks with clear asymmetries of scalp electrical
      discharges.

PMID- 21946368
TI  - Application of electrophysiologic techniques in poor outcome prediction among
      patients with severe focal and diffuse ischemic brain injury.
AB  - OBJECTIVE: To explore various electrophysiologic examinations as predictors for
      poor outcome in patients with severe ischemic brain injury, by comparing the
      prognostic ability of EEG, short-latency somatosensory evoked potentials (SLSEP),
      and brain stem auditory evoked potentials (BAEP). METHODS: EEG, SLSEP, and BAEP
      were recorded in 161 patients with severe ischemic brain injuries (Glasgow Coma
      Scale <= 8), 77 with anoxic-ischemic encephalopathy after cardiopulmonary
      resuscitation, while 84 experienced massive hemispheric infarction at between 1
      and 7 days after the onset. Outcomes were reviewed after 6 months using the
      Glasgow Outcome Scale. RESULTS: Six months after the onset, poor outcomes
      (Glasgow Outcome Scale, 1-2) were identified in 66 and 54 patients among the
      anoxic-ischemic encephalopathy and the massive hemispheric infarction group,
      respectively. By using the prognostic authenticity analysis of predictors,
      unfavorable EEG patterns, lack of EEG reactivity, pathologic N20 of SLSEP, and
      pathologic wave V of BAEP showed the high sensitivity (92.4%-97.0%, 95%
      confidence interval [CI]: 82.5%-99.5%), while bilateral absence of SLSEP N20
      showed the highest specificity (100%, 95% CI: 67.9%-100%) and positive predictive
      value (100%, 95% CI: 90.4%-100%) in the anoxic-ischemic encephalopathy group. In
      the massive hemispheric infarction group, unfavorable EEG patterns showed the
      highest sensitivity (96.3%, 95% CI: 86.2%-99.4%) while bilateral absence of SLSEP
      N20 and BAEP wave V showed the highest specificity (100%, 95% CI: 85.9%-100%) and
      positive predictive value (100%, 95% CI: 80.8%-100%). CONCLUSIONS: The predictive
      power of electrophysiologic examinations is different according to the etiology
      of ischemic brain injury. Short-latency somatosensory evoked potentials (N20) can
      be considered the most powerful method to predict poor outcome in anoxic-ischemic
      encephalopathy. Combination of EEG (unfavorable EEG patterns) and SLSEP
      (N20)/BAEP (wave V) is best suited in massive hemispheric infarction to predict
      poor outcome.

PMID- 21946370
TI  - Evolution of genuine cross-correlation strength of focal onset seizures.
AB  - To quantify the evolution of genuine zero-lag cross-correlations of focal onset
      seizures, we apply a recently introduced multivariate measure to broad band and
      to narrow-band EEG data. For frequency components below 12.5 Hz, the strength of
      genuine cross-correlations decreases significantly during the seizure and the
      immediate postseizure period, while higher frequency bands show a tendency of
      elevated cross-correlations during the same period. We conclude that in terms of
      genuine zero-lag cross-correlations, the electrical brain activity as assessed by
      scalp electrodes shows a significant spatial fragmentation, which might promote
      seizure offset.

PMID- 21946369
TI  - Comparison of three methods for localizing interictal epileptiform discharges
      with magnetoencephalography.
AB  - PURPOSE: To compare three methods of localizing the source of epileptiform
      activity recorded with magnetoencephalography: equivalent current dipole, minimum
      current estimate, and dynamic statistical parametric mapping (dSPM), and to
      evaluate the solutions by comparison with clinical symptoms and other
      electrophysiological and neuroradiological findings. METHODS: Fourteen children
      of 3 to 15 years were studied. Magnetoencephalography was collected with a whole
      head 204-channel helmet-shaped sensor array. We calculated equivalent current
      dipoles and made minimum current estimate and dSPM movies to estimate the
      cortical distribution of interictal epileptiform discharges in these patients.
      RESULTS: The results for four patients with localization-related epilepsy and one
      patient with Landau-Kleffner Syndrome were consistent among all the three
      analysis methods. In the rest of the patients, minimum current estimate and dSPM
      suggested multifocal or widespread activity; in these patients, the equivalent
      current dipole results were so scattered that interpretation of the results was
      not possible. For 9 patients with localization-related epilepsy and generalized
      epilepsy, the epileptiform discharges were wide spread or only slow waves, but
      dSPM suggested a possible propagation path of the interictal epileptiform
      discharges. CONCLUSION: Minimum current estimate and dSPM could identify the
      propagation of epileptiform activity with high temporal resolution. The results
      of dSPM were more stable because the solutions were less sensitive to background
      brain activity.

PMID- 21946371
TI  - Shoulder pain and an isolated teres minor nerve lesion.
AB  - The finding of isolated teres minor denervation during examination of the
      shoulders using MRI occurs in 3% to 5.5% of examinations. We describe eight
      patients with shoulder pain, in whom electromyography revealed an isolated lesion
      in the motor branch of the axillary nerve to the teres minor muscle. This nerve
      lesion is clinically impossible to diagnose, the lack of a clear diagnosis often
      resulting in inappropriate treatment and therefore potentially prolonged
      disability. Hence, when encountering shoulder problems, neurophysiologists should
      examine the teres minor muscle as a matter of routine. In the MRI and ultrasound
      examinations of patients with shoulder problems, therefore, not only routine
      tendon and joint structure but also muscles should be evaluated.

PMID- 21946372
TI  - Usefulness of standard EEG in predicting the outcome of patients with disorders
      of consciousness after anoxic coma.
AB  - Although standard EEG is performed routinely in patients with disorders of
      consciousness after coma, its prognostic value is still debated. The aim of the
      present study was to evaluate the role of standard EEG in predicting the recovery
      of cognitive functioning in patients affected by severe disturbances of
      consciousness after coma caused by cerebral anoxia. A standard EEG was recorded
      at admission to our Rehabilitation Department in 15 patients experiencing
      impaired consciousness because of cerebral anoxia. We quantified EEG
      abnormalities using the Synek scale (1988). Cognitive functioning was measured
      with the levels of cognitive functioning scale at the time of admission and after
      3 months of recovery. EEG scores were significantly correlated with both levels
      of cognitive functioning scores at admission (P = 0.004) and change in levels of
      cognitive functioning score after 3 months (P < 0.001). The first correlation
      confirms the relationship between EEG and cognitive functioning, while the second
      correlation indicates the prognostic value of EEG in cognitive outcome. In
      conclusion, standard EEG is a simple and readily available tool with significant
      prognostic value in patients with disorders of consciousness after coma caused by
      cerebral anoxia.

PMID- 21946373
TI  - Generalized paroxysmal fast activity and tonic seizures in older adults.
AB  - Generalized paroxysmal fast activity is an uncommon ictal EEG pattern usually
      associated with tonic seizures. Patients with generalized paroxysmal fast
      activity typically have multiple seizure types beginning in childhood and are
      refractory to antiepileptic drug therapy. We describe 3 hospitalized adult
      patients (age, older than 55 years) with new-onset tonic movements, noted during
      an acute illness, associated with generalized paroxysmal fast activity on EEG.
      These seizures were characterized by subtle stiffening of the arms, trunk, and
      face for up to 3 seconds. All patients had multiple medical problems and
      polypharmacy. None had a history of static encephalopathy, other epileptiform
      abnormalities on EEG, other seizure types, or significant neuroimaging
      abnormalities. In contrast to previously described reports in children, all three
      adults responded to antiepileptic drug monotherapy. EEG played a critical role in
      differentiating tonic seizures from nonepileptic movements in these three cases.

PMID- 21946374
TI  - Asymmetry of motor unit number estimate and its rate of decline in patients with
      amyotrophic lateral sclerosis.
AB  - This study was performed to investigate the asymmetry of motor unit number
      estimate (MUNE) and its longitudinal course in patients with amyotrophic lateral
      sclerosis. A modified statistical MUNE was performed at the hypothenar muscles
      bilaterally in a total of 135 patients, and 18 of these patients underwent a
      follow-up study. The degree of asymmetry varied considerably among those patients
      whose average MUNE of both sides was moderately reduced, whereas it tended to be
      low in those whose average MUNE was either severely reduced or close to normal.
      The rate of motor unit loss was also asymmetric, and two distinct patterns were
      identified. In patients whose MUNE was greater than 30 in both sides (n = 7), the
      rate of motor unit loss tended to be greater in the initially more affected side
      compared with the contralateral one, yielding the so-called lead phenomenon. In
      contrast, the other patients (n = 11) tended to show the opposite pattern of
      "catch-up," that is, MUNE declined faster in the initially less affected side
      compared with the contralateral one. This study shows that not only the MUNE but
      also the rate of motor unit loss are frequently asymmetric in amyotrophic lateral
      sclerosis patients.

PMID- 21946375
TI  - Aberrant EEG rhythms and epilepsy.

PMID- 21946377
TI  - Physiologic pseudoseizure:  misreading the EEG.

PMID- 21946379
TI  - Bone marrow may be the preferable graft source in recipients homozygous for HLA-C
      group 2 ligands for inhibitory killer Ig-like receptors.
AB  - HLA class I molecules participate in natural killer cell regulation by acting as
      ligands for inhibitory killer cell Ig-like receptors (KIRs). One individual may
      express one or more inhibitory KIR lacking the corresponding HLA ligand. The role
      of this 'missing KIR ligand' constellation in hematopoietic SCT (HSCT) remains
      controversial and depends on incompletely defined transplant variables. We have
      retrospectively analyzed the effects of missing HLA-C group 1/2 and Bw4 KIR
      ligands in the recipients on the outcome in 382 HSCT, comparing 118 BMT to 264
      PBSC transplants (PBSCT). In the multivariate Cox analysis of PBSCT, poor PFS was
      observed in homozygous HLA-C group 2 (C2/2) recipients (risk ratio (RR), 1.59;
      P=0.026). In contrast, C2 homozygosity was not unfavorable after BMT (RR, 0.68;
      P=0.16). C2 homozygous recipients (n=68) had better PFS after BMT than after
      PBSCT (RR, 0.17; P=0.001), due to fewer relapses (RR, 0.27; P=0.018). Missing Bw4
      favorably influenced PFS after BMT (RR, 0.56; P=0.04), but not after PBSCT. These
      data suggest opposite effects of missing KIR ligands in BMT vs PBSCT. Larger
      studies are required to reassess whether BMT should be preferred to PBSCT as an
      option for C2/C2 recipients.

PMID- 21946380
TI  - Experience (1 year) of G-CSF biosimilars in PBSCT for lymphoma and myeloma
      patients.

PMID- 21946381
TI  - Effect of acute and chronic GVHD on relapse and survival after reduced-intensity
      conditioning allogeneic transplantation for myeloma.
AB  - We evaluated the effect of acute and chronic GVHD on relapse and survival after
      allogeneic hematopoietic SCT (HSCT) for multiple myeloma using non-myeloablative
      conditioning (NMA) and reduced-intensity conditioning (RIC). The outcomes of 177
      HLA-identical sibling HSCT recipients between 1997 and 2005, following NMA (n=98)
      or RIC (n=79) were analyzed. In 105 patients, autografting was followed by
      planned NMA/RIC allogeneic transplantation. The impact of GVHD was assessed as a
      time-dependent covariate using Cox models. The incidence of acute GVHD (aGVHD;
      grades I-IV) was 42% (95% confidence interval (CI), 35-49%) and of chronic GVHD
      (cGVHD) at 5 years was 59% (95% CI, 49-69%), with 70% developing extensive cGVHD.
      In multivariate analysis, aGVHD (>= grade I) was associated with an increased
      risk of TRM (relative risk (RR)=2.42, P=0.016), whereas limited cGVHD
      significantly decreased the risk of myeloma relapse (RR=0.35, P=0.035) and was
      associated with superior EFS (RR=0.40, P=0.027). aGVHD had a detrimental effect
      on survival, especially in those receiving autologous followed by allogeneic HSCT
      (RR=3.52, P=0.001). The reduction in relapse risk associated with cGVHD is
      consistent with a beneficial graft-vs-myeloma effect, but this did not translate
      into a survival advantage.

PMID- 21946382
TI  - Differences in mothers' and fathers' health-related quality of life after
      pediatric SCT: a longitudinal study.
AB  - The purpose of this study was to examine longitudinally health-related quality of
      life (HRQOL) and related factors in mothers and fathers of children who undergo
      SCT, before, and 1 and 2 years after SCT. A total of 84 parents (49 mothers/35
      fathers) of patients diagnosed mainly with leukemia completed a HRQOL measure
      before SCT, 46 at 1 year (26 mothers/20 fathers) and 50 parents (31 mothers/19
      fathers) at 2 years post SCT. Physical and psychosocial HRQOL summary scores are
      reported. Parents' age and gender, child's diagnosis, radiation history, age,
      behavior and physical health were examined. Linear mixed models for repeated
      measures with a covariate structure were used for analysis. Physical HRQOL did
      not differ between mothers and fathers or over time. Maternal and paternal
      psychosocial HRQOL scores improved by 2 years post SCT. Child's behavior problems
      and poor health, and maternal age (younger) predicted poor maternal psychosocial
      HRQOL 2 years post SCT. Child's behavior problems, diagnosis and treatment
      severity predicted poor paternal psychosocial HRQOL. These findings identify
      similar (child's poor behavior) and differential risk factors (parental young
      age, disease and treatment severity, and child's poor health status) for poor
      HRQOL for mothers and fathers. These findings can guide comprehensive family-care
      interventions before, during and after pediatric SCT.

PMID- 21946384
TI  - Successful treatment with tandem consolidation using 90yttrium-ibritumomab
      tiuxetan (Zevalin) and high-dose therapy with autologous PBSCT in a patient with
      relapsed mantle cell lymphoma presenting as multiple lymphomatous polyposis.

PMID- 21946383
TI  - Factors predicting single-unit predominance after double umbilical cord blood
      transplantation.
AB  - Double umbilical cord blood transplantation (dUCBT), developed as a strategy to
      treat large number of patients with hematologic malignancies, frequently leads to
      the long-term establishment of a new hematopoietic system maintained by cells
      derived from a single umbilical cord blood unit. However, predicting which unit
      will predominate has remained elusive. This retrospective study examined the risk
      factor associated with unit predominance in 262 patients with hematologic
      malignancies who underwent dUCBT with subsequent hematopoietic recovery and
      complete chimerism between 2001 and 2009. Dual chimerism was detected at day 21
      28, with subsequent single chimerism in 97% of the cases by day +100 and beyond.
      Risk factors included nucleated cell dose, CD34+ and CD3+ cell dose, colony
      forming units-granulocyte macrophage dose, donor-recipient HLA match, sex and ABO
      match, order of infusion and cell viability. In the myeloablative setting, CD3+
      cell dose was the only factor associated with unit predominance (odds ratio (OR)
      4.4, 95% confidence interval (CI) 1.8-10.6; P<0.01), but in the non-myeloablative
      setting, CD3+ cell dose (OR 2.1, 95%CI 1.0-4.2; P=0.05) and HLA match (OR 3.4,
      95%CI 1.0-11.4; P=0.05) were independent factors associated with unit
      predominance. Taken together, these findings suggest that immune reactivity has a
      role in unit predominance, and should be considered during graft selection and
      graft manipulation.

PMID- 21946385
TI  - Coffee and amyotrophic lateral sclerosis: a possible preventive role.
AB  - The relation between coffee intake and risk of amyotrophic lateral sclerosis
      (ALS) was investigated in 377 newly diagnosed ALS patients from 4 Italian
      population-based registries in the European ALS Consortium (EURALS Group) (2007
      2010). For each patient, 2 age- and sex-matched hospital controls were selected,
      one from a neurology department and one from a nonneurologic department. Two
      additional healthy control groups were identified from local general
      practitioners' (GPs') lists (n = 99) and residents of the same area as a cancer
      cohort (n = 7,057). Coffee intake was defined in terms of status (ever consuming
      coffee daily for >=6 months vs. never), duration, and history (never, former, or
      current). Ever coffee drinkers comprised 74.7% of ALS patients, 80.4% of
      neurologic controls, 85.6% of nonneurologic controls (P = 0.0004), 88.9% of GP
      controls (P = 0.0038), and 86.0% of cancer cohort controls (P < 0.0001). Current
      coffee drinkers comprised 60.2% of ALS patients, 70.2% of neurologic controls (P
      = 0.0294), 76.4% of nonneurologic controls (P < 0.0001), and 82.3% of GP controls
      (P = 0.0002); duration of intake was >=30 years for 62.3%, 67.7%, 74.7%, and
      72.6%. ALS patients had lower lifetime coffee exposure: Odds ratios were 0.7 (95%
      confidence interval (CI): 0.5, 1.1), 0.6 (95% CI: 0.4, 0.8), and 0.4 (95% CI:
      0.2, 0.9) in comparison with neurologic, nonneurologic, and GP controls,
      respectively. In current (vs. never) coffee drinkers, odds ratios were 0.7 (95%
      CI: 0.5, 1.0), 0.5 (95% CI: 0.3, 0.7), and 0.4 (95% CI: 0.2, 0.8), respectively.
      These findings provide epidemiologic evidence of an inverse correlation between
      coffee intake and ALS risk.

PMID- 21946386
TI  - On the pitfalls of adjusting for gestational age at birth.
AB  - Preterm delivery is a powerful predictor of newborn morbidity and mortality. Such
      problems are due to not only immaturity but also the pathologic factors (such as
      infection) that cause early delivery. The understanding of these underlying
      pathologic factors is incomplete at best. To the extent that unmeasured
      pathologies triggering preterm delivery also directly harm the fetus, they will
      confound the association of early delivery with neonatal outcomes. This, in turn,
      complicates studies of newborn outcomes more generally. When investigators
      analyze the association of risk factors with neonatal outcomes, adjustment for
      gestational age as a mediating variable will lead to bias. In the language of
      directed acyclic graphs, gestational age is a collider. The theoretical basis for
      colliders has been well described, and gestational age has recently been
      acknowledged as a possible collider. However, the impact of this problem, as well
      as its implications for perinatal research, has not been fully appreciated. The
      authors discuss the evidence for confounding and present simulations to explore
      how much bias is produced by adjustments for gestational age when estimating
      direct effects. Under plausible conditions, frank reversal of exposure-outcome
      associations can occur. When the purpose is causal inference, there are few
      settings in which adjustment for gestational age can be justified.

PMID- 21946387
TI  - Integration of genome-wide transcriptional and genetic profiles provides insights
      into disease development and clinical heterogeneity in alopecia areata.
AB  - Alopecia areata (AA), a non-scarring inflammatory hair loss disorder, is a
      complex disease determined by genetic and environmental factors that remain
      largely unknown. Re-analysis of genome-wide microarray data in 9 patient blood
      and 10 skin samples revealed transcriptional "hot spots" at chromosomes 1q21-q32,
      11q12-q14, and 16p13-p13.3 (blood) and 6p21.3, 12q12-q13, and 17q12-q24 (skin)
      harboring high densities of dysregulated genes. We then integrated AA associated
      gene expression profiles with previous genome-wide genetic analyses to identify a
      subset of 112 dysregulated genes that map to putative susceptibility loci.
      Finally, we analyzed AA patients stratified by defined clinical characteristics,
      including a history of atopy, autoimmune disease, and nail disease, thus
      deconstructing the clinical heterogeneity observed among AA patients. Integrated
      chromosomal and transcriptional profiling identified several dysregulated
      chromosomal regions and genes representing an enriched set of biomarkers relevant
      to AA pathogenesis and clinical heterogeneity.

PMID- 21946388
TI  - Catheter ablation of atrial fibrillation in patients with chronic lung disease.
AB  - BACKGROUND: Chronic lung disease (CLD) is one of the important underlying
      diseases of atrial fibrillation (AF). The outcomes after radiofrequency catheter
      ablation of AF in patients with CLD have not yet been reported. We investigated
      the electroanatomic alterations in pulmonary veins (PVs) in CLD patients with AF
      and assessed their effect on the outcomes of radiofrequency catheter ablation of
      AF. METHOD AND RESULTS: We assessed 15 patients who had CLD and underwent
      radiofrequency catheter ablation of AF. CLD included chronic obstructive
      pulmonary disease, a tuberculosis-destroyed lung, and interstitial lung disease.
      For controls, we selected 60 sex-, age-, and procedure era-matched non-CLD
      patients who received radiofrequency catheter ablation for AF (4 controls for
      each CLD patient). Eight patients had chronic obstructive pulmonary disease, 6
      had a tuberculosis-destroyed lung, and 1 had interstitial lung disease. PV
      morphology in the affected lung was altered significantly, ie, obliteration,
      pulling of the PVs toward the destroyed lung, or compensatory bulging of the PV
      antrum. These alterations were related to arrhythmogenicity in 6 (40%) of 15
      patients with CLD. Non-PV foci were more common in the CLD group (4/15, 26.7%)
      than in the control group (3/60, 5.0%; P=0.025). All non-PV foci were located in
      the right atrium. The AF recurrence rate in the CLD group (26.7%, 4/15) was
      similar to that in the control group (18.3%, 11/60; P=0.45). CONCLUSIONS:
      Significant alteration of PV anatomy was related to arrhythmogenicity, and non-PV
      foci from the right atrium were commonly observed in the CLD group.
      Radiofrequency catheter ablation can be performed safely for AF in CLD patients
      with a comparable success rate to that in patients with normal lungs.

PMID- 21946389
TI  - New insights into HCV replication: potential antiviral targets.
AB  - The ultimate goal of hepatitis C virus (HCV) treatment is the eradication of the
      virus. Ongoing research continues to add to knowledge of the HCV life cycle,
      revealing new potential viral and host targets for the development of therapy.
      Understanding of HCV was initially hampered by the inability to achieve viral
      replication in cell culture. Advances such as the HCV replicon and complete cell
      culture systems, however, have permitted rapid growth in knowledge and
      accelerated testing of candidate antiviral agents. Among potential targets are
      viral entry factors, including scavenger receptor type B1 (SR-B1) and CD81, as
      well as neutralizing antibodies against the viral glycoproteins. Popular targets
      related to translation and replication are the NS3/4A protease (inhibited by
      telaprevir and boceprevir) and the NS5B polymerase, as well as the NS2/3
      autoprotease, the NS3 helicase, and nonenzymatic targets such as NS4B and NS5A
      proteins. Host targets are also available, including microRNAs and cyclophilins.
      This article summarizes a presentation by Charles M. Rice, PhD, at the IAS-USA
      live continuing medical education course, Management of Hepatitis C Virus in the
      New Era: Small Molecules Bring Big Changes, held in New York City in April 2011.

PMID- 21946390
TI  - Advanced liver disease: what every hepatitis C virus treater should know.
AB  - Identification and treatment of advanced hepatitis C virus (HCV) infection is
      often challenging. Accurate fibrosis staging can be performed only by liver
      biopsy. For patients with advanced fibrosis (Metavir score, F3 or F4),
      progression to decompensated liver disease occurs at a rate of approximately 5%
      per year and progression to hepatocellular carcinoma occurs at a rate of 1% to 2%
      per year. Liver decompensation primarily results from altered hepatic blood flow
      caused by liver scarring and is characterized by ascites and its complications
      (hepatorenal syndrome, hepatic hydrothorax, and spontaneous bacterial
      peritonitis), hepatic encephalopathy, bleeding varices, and coagulopathy.
      Patients with advanced fibrosis need to be regularly monitored for evidence of
      decompensated disease, and complications need to be aggressively managed. This
      article summarizes a presentation by Kenneth E. Sherman, MD, at the IAS-USA live
      continuing medical education course, Management of Hepatitis C Virus in the New
      Era, held in New York City in April 2011.

PMID- 21946392
TI  - Addition of aliskiren to olmesartan ameliorates tubular injury in chronic kidney
      disease patients partly by reducing proteinuria.
AB  - INTRODUCTION: Tubular injury is more important than glomerulopathy for renal
      prognosis in chronic kidney disease (CKD) patients. Numerous studies have
      demonstrated the active participation of the renin-angiotensin system (RAS) in
      CKD. However, whether addition of aliskiren, a direct renin inhibitor, to
      olmesartan improves renal tubular injury in CKD patients is unknown. METHODS:
      This study compared the effects of aliskiren (300 mg daily), olmesartan (40 mg
      daily), and its combination therapy on urinary L-fatty acid binding protein (L
      FABP), a marker of tubular injury in stage I or II CKD patients. It also examined
      which clinical variables were independently correlated with tubular damage.
      RESULTS: Olmesartan or aliskiren monotherapy for 6 months comparably decreased
      blood pressure (BP) and proteinuria. BP and proteinuria levels were reduced more
      by combination therapy than by either monotherapy. Olmesartan or aliskiren
      decreased urinary L-FABP level, and combination therapy produced more incremental
      reduction in L-FABP level relative to each monotherapy. Multiple stepwise
      regression analysis revealed that BMI, low-density lipoprotein (LDL)-cholesterol
      and proteinuria were independently related to urinary L-FABP level. CONCLUSIONS:
      The present study demonstrated that addition of aliskiren to olmesartan decreased
      urinary L-FABP level partly via reduction of proteinuria in stage I or II CKD
      patients.

PMID- 21946391
TI  - When patients cannot take pills: antiretroviral drug formulations for managing
      adult HIV infection.
AB  - Providing antiretroviral therapy for the HIV-infected population is a complex and
      challenging task. Treatment is often complicated by the shifting demographic of
      HIV-infected patients that now includes a large aging population in which
      patients often have multiple comorbidities. HIV clinicans are challenged with
      choosing the optimal combination of antiretrovirals based on potency,
      tolerability, bioavailability, and ease of administration. The issue of
      bioavailability is of paramount importance for those patients who can't swallow
      tablets, are unable to take anything by mouth before a procedure, or who need
      medication through a nasogastric tube or percutaneous endoscopic gastrostomy
      tube. A thorough search of several drug databases, a literature search of MEDLINE
      through Ovid, and a review of full prescribing information for each currently
      available antiretroviral drug, was performed to obtain insight into the
      bioavailability of antiretrovirals. Implications for the findings are discussed
      as they relate to adherence, resistance, alternative methods of administration,
      and the sometimes conflicting information on bioavailability that exists for
      various antiretroviral agents.

PMID- 21946393
TI  - A meta-analysis of the association between angiotensin-converting enzyme
      insertion/deletion gene polymorphism and steroid-sensitive nephrotic syndrome in
      children.
AB  - BACKGROUND AND OBJECTIVE: Angiotensin-converting enzyme (ACE) insertion/deletion
      (I/D) gene polymorphism correlates with circulating and cellular ACE
      concentration. Association between ACE I/D gene polymorphism and steroid
      sensitive nephrotic syndrome (SSNS) risk in children is still controversial. This
      meta-analysis was performed to evaluate the relation between ACE I/D gene
      polymorphism and SSNS susceptibility in children. METHODS: The relevant
      investigations were screened from the search engines of PubMed, Cochrane Library
      and CBM-disc (China Biological Medicine Database) as of 1 March 2011, and
      eligible studies were synthesized using meta-analysis methods. RESULTS: Ten
      studies were identified for the analysis of association between ACE I/D gene
      polymorphism and SSNS risk in children, including seven in Asians, one for
      Caucasians and two in Africans. There was no markedly positive association
      between D allele or DD genotype and SSNS susceptibility in Asians, Caucasians and
      Africans (D: Asians OR = 1.24, p = 0.28; Caucasians OR = 1.61, p = 0.15; Africans
      OR = 1.61, p = 0.53; DD: Asians OR = 1.72, p = 0.15; Caucasians OR = 1.39, p =
      0.48; Africans OR = 1.80, p = 0.56). Furthermore, II homozygous seemed not to
      play a protective role against SSNS onset for Asians, Caucasians and Africans
      (Asians OR = 0.95, p = 0.85; Caucasians OR = 0.30, p = 0.11; Africans OR = 0.60,
      p = 0.65). CONCLUSIONS: There was no association between ACE I/D gene
      polymorphism and SSNS susceptibility in Asians, Caucasians and Africans. However,
      the conclusions for Caucasians and Africans were less powerful.

PMID- 21946394
TI  - Association of angiotensin converting enzyme insertion/deletion gene polymorphism
      with idiopathic nephrotic syndrome susceptibility in children: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: Angiotensin converting enzyme (ACE) gene contains
      either an insertion (I) allele or a deletion (D) allele forming three potential
      genotypes: II, ID and DD. The D allele or DD genotype has been reported to be
      associated with higher plasma ACE level. An assessment of the association between
      ACE I/D gene polymorphism and idiopathic nephrotic syndrome (INS) susceptibility
      in children is still controversial. This meta-analysis was performed to evaluate
      the association between ACE I/D gene polymorphism and the onset of INS. METHOD: A
      predefined literature search and selection of eligible relevant studies were
      performed to collect data from electronic databases, and eligible investigations
      were synthesized using the meta-analysis method. RESULTS: Nine investigations
      were identified for the analysis of association between ACE I/D gene polymorphism
      and INS risk in children, including six in Asians, one study for Caucasians and
      two for Africans. There was positive association between D allele or DD genotype
      and INS susceptibility in Asians (OR = 1.75, p = 0.01; OR = 2.01, p = 0.02), but
      not for Caucasian children and Africans (for Caucasians, D: OR=1.35, p = 0.27,
      DD: OR = 0.95, p = 0.91; for Africans, D: OR = 1.70, p = 0.56, DD: OR = 1.60, p =
      0.73). Furthermore, II homozygous seemed to play a positive role against INS
      onset for Asians (OR = 0.59, p = 0.02), but the link between II genotype and INS
      risk was not observed in Caucasian children and Africans (Caucasians: OR = 0.31,
      p = 0.06; Africans: OR = 0.50, p = 0.59). CONCLUSIONS: D allele and DD homozygous
      might become significant genetic molecular markers for INS susceptibility in
      Asian children, but the association was not observed in Caucasians or Africans.
      However, the conclusion from our study cannot be sustained and more
      investigations on larger sample in different populations are required to further
      clarify the role of D allele or DD homozygous in the onset of INS in difference
      races.

PMID- 21946396
TI  - Microcystin-LR acute exposure increases AChE activity via transcriptional ache
      activation in zebrafish (Danio rerio) brain.
AB  - Microcystins (MCs) constitute a family of cyanobacterial toxins, with more than
      80 variants. These toxins are able to induce hepatotoxicity in several organisms
      mainly through the inhibition of protein phosphatases PP1 and PP2A and oxidative
      stress generation. Since recent evidence shows that MCs can either accumulate in
      brain or alter behavior patterns of fish species, in this study we tested the in
      vitro and in vivo effects of MC-LR at different concentrations on
      acetylcholinesterase (AChE) activity in zebrafish brain. In vivo studies showed
      that 100 MUg/L MC-LR led to a significant increase in the AChE activity (27%)
      when zebrafish were exposed to the toxin dissolved in water, but did not cause
      any significant changes when injected intraperitoneally. In addition,
      semiquantitative RT-PCR analysis demonstrated that 100 MUg/L MC-LR exposure also
      increased ache mRNA levels in zebrafish brain. The in vitro assays did not reveal
      any significant changes in AChE activity. These findings provide the first
      evidence that brain AChE is another potential target for MCs and suggest that the
      observed increases in AChE enzymatic activity and in ache transcript levels after
      MC-LR exposure depend, at least partially, on branchial uptake or ingestion.

PMID- 21946397
TI  - Chromatin specialization in bivalve molluscs: a leap forward for the evaluation
      of Okadaic Acid genotoxicity in the marine environment.
AB  - Marine biotoxins synthesized by Harmful Algal Blooms (HABs) represent one of the
      most important sources of contamination in marine environments as well as a
      serious threat to fisheries and aquaculture-based industries in coastal areas.
      Among these biotoxins Okadaic Acid (OA) is of critical interest as it represents
      the most predominant Diarrhetic Shellfish Poisoning biotoxin in the European
      coasts. Furthermore, OA is a potent tumor promoter with aneugenic and clastogenic
      effects on the hereditary material, most notably DNA breaks and alterations in
      DNA repair mechanisms. Therefore, a great effort has been devoted to the
      biomonitoring of OA in the marine environment during the last two decades, mainly
      based on physicochemical and physiological parameters using mussels as sentinel
      organisms. However, the molecular genotoxic effects of this biotoxin make
      chromatin structure a good candidate for an alternative strategy for toxicity
      assessment with faster and more sensitive evaluation. To date, the development of
      chromatin-based studies to this purpose has been hampered by the complete lack of
      information on chromatin of invertebrate marine organisms, especially in bivalve
      molluscs. Our preliminary results have revealed the presence of histone variants
      involved in DNA repair and chromatin specialization in mussels and clams. In this
      work we use this information to put forward a proposal focused on the development
      of chromatin-based tests for OA genotoxicity in the marine environment. The
      implementation of such tests in natural populations has the potential to provide
      an important leap in the biomonitoring of this biotoxin. The outcome of such
      monitoring may have critical implications for the evaluation of DNA damage in
      these marine organisms. They will provide as well important tools for the
      optimization of their harvesting and for the elaboration of additional tests
      designed to evaluate the safety of their consumption and potential implications
      for consumer's health.

PMID- 21946398
TI  - An outstanding first Impact Factor of 2.246 for the European Journal of Physical
      and Rehabilitation Medicine, Official Journal of SIMFER, ESPRM, and MFPMR, and
      now also published "in association with" ISPRM.

PMID- 21946399
TI  - Are ultrasound, laser and exercise superior to each other in the treatment of
      subacromial impingement syndrome? A randomized clinical trial.
AB  - BACKGROUND: Subacromial impingement syndrome (SIS) is the most common reason for
      shoulder pain. Ultrasound and laser are the physical therapy modalities, in
      conservative treatment of SIS. AIM: The aim of this study was to define and
      compare the efficacy of ultrasound, laser and exercise in the treatment of SIS.
      DESIGN: This was a randomized controlled trial with-pre and post-treatment
      evaluations SETTING: Out-patients referred to physical medicine and
      rehabilitation unit. POPULATION: This study was performed on 52 patients with
      SIS. The patients were randomly allocated into three groups METHODS: The patients
      were treated five days a week for three weeks with hotpack+ultrasound+exercise
      (the first group); hotpack+laser+exercise (the second group), or hotpack+exercise
      (the third group). The pre and post treatment ranges of motion were measured in
      the patients. The visual analogue scale (VAS) was used to evaluate the severity
      of pain. Constant scoring was used to evaluate the shoulder functions and the
      results were compared after the treatment. RESULTS: When the post-treatment
      results of the groups were compared with the pretreatment results, there was a
      statistically significant improvement in each of the three groups, in the pain,
      the range of motion and the functional improvement at the shoulder (P<0.05).
      However, the inter-group comparison did not reveal any statistically significant
      difference in the parameters indicating improvement (P>0.05). CONCLUSION: The
      results of this study demonstrated that ultrasound and laser treatments were not
      superior to each other in the treatment of SIS. CLINICAL REHABILITATION IMPACT: .
      Exercise treatment forms the base for the conservative treatment.

PMID- 21946400
TI  - Comparison of the effects of low energy laser and ultrasound in treatment of
      shoulder myofascial pain syndrome: a randomized single-blinded clinical trial.
AB  - BACKGROUND: Myofascial pain syndrome (MPS) is one of the most prevalent
      musculoskeletal diseases. MPS impaired quality of life in the patients. There is
      a lot of controversy about different treatment options which include medical
      treatments, physical therapy, injections, ultrasound and laser. The effects of
      laser in MPS are challenging. AIM: To assess the effects of laser and ultrasound
      in treatment of MPS. DESIGN: Randomized single blinded clinical trial SETTING:
      Outpatient physical therapy clinic at university hospital POPULATION: Sixty three
      subjects (females: 46, males: 17), (age range: 17-55 year old) who had a
      diagnosis of definite MPS were entered in the study. METHODS: We measured the
      pain intensity at rest, during activity and at night using Visual Analogue Scale
      (VAS) questionnaire. The patients also filled the Neck Disability Index (NDI)
      form and the pain threshold provoked by pressure was determined using algometric
      assessment. Then, the patients were categorized randomly in groups A, B and C
      (receiving laser therapy, ultrasound and sham laser therapy, respectively). Six
      weeks after the initial visit, they were visited again and filled the forms
      again. RESULTS: Ultrasound was effective in VAS improvement during activity
      (46%), at rest (39%) and at night (35%). It also improved NDI scores (34%) and
      algometric assessment (37%). Laser was effective in VAS improving during activity
      (54%), at night (51%) and at rest (51%) and also improved NDI scores (73%). It
      was also found effective in algometric assessment improvement (105%). Laser
      resulted in more NDI score and algometric assessment improvements comparing to
      ultrasound (p<0.05). CONCLUSION: This study introduces laser as one of the
      preferred treatments of myofascial pain syndrome in shoulder.

PMID- 21946401
TI  - A prospective observational study of the clinical efficacy and safety of intra
      articular sodium hyaluronate in synovial joints with osteoarthritis.
AB  - BACKGROUND: Clinical trials have demonstrated the safety and efficacy of
      hyaluronic acid-based products for the treatment of synovial joints affected by
      osteoarthritis (OA), but data from observational studies of normal medical
      practice are sparse. AIM: This study investigated the safety and efficacy of
      intra-articular (IA) sodium hyaluronate (MW 1500-2000 KDa; Hyalubrix(r)) in the
      treatment of synovial joint OA. DESIGN: This is prospective, and observational
      study. SETTING: This study was carried out at 47 specialist centers for
      physiatrists, orthopedics and rheumatology in Italy; the enrolled population,
      1266 outpatient, was predominantly female (66%, 840/1266), with a mean age of 66
      years, and a mean weight of 74 kg. POPULATION: The Participants with OA received
      IA injections of the study treatment (2 mL) once per week for 3 weeks. The knee
      was the joint most commonly affected by OA (right knee 802/1266 [63%]; left knee
      598/1266 [47%]), and the longest median duration of disease occurred in the
      carpal joint (right carpal joint 40 months; left carpal joint 60 months).
      METHODS: The primary endpoints were tolerability and details of usage of the IA
      sodium hyaluronate syringe device. Efficacy parameters included assessment of
      self-reported pain via the Visual Analogue Scale (VAS), and evaluation of motor
      function via the Health Assessment Questionnaire (HAQ). Quality of life (QoL) was
      assessed using the Euro QoL questionnaire (Clinical Trial Registration Number:
      ISRCTN 42690497). RESULTS: Data from 1266 participants were collected. The
      adverse event (AE) rate was 0.8% (95% CI, 0.4 to 1.5). Thirteen AEs were
      reported, 12 of which were mild or moderate in severity. Only one participant
      discontinued study treatment following an AE. No serious adverse events occurred.
      Coadministration of local anesthetic was required by up to 10% of patients.
      Statistically significant improvements in VAS, HAQ and EuroQoL were recorded in
      multiple joints (P<0.0001 for each). CONCLUSION: The study treatment was safe and
      well tolerated. CLINICAL REHABILITATION IMPACT: . The study treatment reduced
      pain, improved mobility, and increased QoL in participants with OA.

PMID- 21946402
TI  - Bibliometric indicators: a snapshot of the scientific productivity of leading
      European PRM researchers.
AB  - AIM: The aim of this paper was to explore the validity and practical usefulness
      of a set of bibliometric indicators with a focus on the scientific production of
      influential European researchers in Physical and Rehabilitation Medicine (PRM).
      METHODS: We randomly selected 24 European PRM specialists from the list of
      invited lecturers or chairpersons at the 17th ESPRM Congress in 2010. Using the
      time window 1996-2010, we recorded the number of papers published, total number
      of citations, and h-index from Web of Science (WoS) and Publish or Perish (PoP)
      databases. We also noted the journals in which the papers were published. Ranking
      the 24 authors into two groups according to higher vs. lower research
      productivity, we compared the frequency of Editorial Board membership of at least
      one of the 5 most influential journals in PRM. RESULTS: Median values (WoS, PoP)
      for papers, citations, and h-index were respectively: (31, 46); (171, 317); and
      (6.5, 8.5). High correlations were found among different indicators, and also
      between the same indicators calculated in the two different databases. However,
      the Bland-Altman plot indicated that the two databases could not be considered
      interchangeable. Twelve PRM specialists were Editorial Board members: 11 of them
      were in the first 10 ranking positions for at least one of the 6 indicators
      analysed. CONCLUSION: There is need to better understand the characteristics of
      bibliometric indicators and we retain that the information they provide is
      insufficiently valid to justify their use as the sole objective criterion for
      career assessment.

PMID- 21946403
TI  - Pulmonary rehabilitation.

PMID- 21946404
TI  - Scope, background and definition of pulmonary rehabilitation.
AB  - The optimal therapy of an individual with chronic respiratory disease usually
      requires a combination of pharmacologic and non-pharmacologic therapies. A case
      of a 68-year-old man with advanced chronic obstructive pulmonary disease is given
      to illustrate this point. He is a recent ex-smoker with severe chronic
      obstructive pulmonary disease by spirometric criteria, frequent exacerbations of
      this disease, considerable recent health care utilization, dyspnea with minimal
      activities, severe functional status limitation, prominent systemic effects of
      the disease (e.g., weight loss) and substantial comorbidities. The primary
      respiratory disease cannot be isolated from and treated independently of these
      important factors. Pulmonary rehabilitation is an important therapeutic option in
      situations like this, providing a mode of integrating care, complementing
      otherwise standard medical therapy, and producing significant gains across
      multiple outcome areas of importance to the patient. Pulmonary rehabilitation has
      been defined by the American Thoracic Society and European Respiratory Society
      as: "an evidence-based, multidisciplinary, and comprehensive intervention for
      patients with chronic respiratory diseases who are symptomatic and often have
      decreased daily life activities. Integrated into the individualized treatment of
      the patient, pulmonary rehabilitation is designed to reduce symptoms, optimize
      functional status, increase participation, and reduce health care costs through
      stabilizing or reversing systemic manifestations of the disease". Its components
      include comprehensive assessment, education, exercise training, and psychosocial
      intervention. Outcomes assessment is usually performed for quality assessment.
      Pulmonary rehabilitation produces the greatest improvements of any available
      therapy in dyspnea, exercise capacity, and health-related quality of life. These
      gains are realized despite the fact that pulmonary rehabilitation has no direct
      effect on lung function. It works primarily through reducing the impact of the
      systemic manifestations of the disease and frequent comorbidity. Pulmonary
      rehabilitation also leads to substantial reductions in subsequent health care
      utilization, possibly through collaborative self-management strategies emphasized
      in the program. Although pulmonary rehabilitation has been utilized by astute
      clinicians for many years, its science has been developed over the past two
      decades.

PMID- 21946405
TI  - Process of pulmonary rehabilitation and program organization.
AB  - Pulmonary rehabilitation programs are highly directed to return patients
      suffering from chronic lung diseases to a state of self-help. These programs are
      largely organized as temporary interventions in a highly fragmented delivery care
      system for patients with chronic respiratory conditions. In an optimal health
      care organizational structure, pulmonary rehabilitation needs to be considered as
      an essential part of an individualized, integrated care process, organized from
      the vantage point of the patient and the patients'health continuum. Pulmonary
      rehabilitation programs need to become organized as patient-centered care,
      respectful of and responsive to individual patient preferences, needs and values.
      Partnering and communication skills are considered as drivers for successful
      rehabilitation. Assessment is considered as the cornerstone to evaluate the
      individual needs and problems in order to develop an individualized intervention.
      Pulmonary rehabilitation programs need to move away from a supply-driven
      functional organizational structure towards integrated structures, including the
      full range of medical expertise, technical skills and specialized facilities
      needed to compete on added value in the management of patients with chronic
      respiratory diseases.

PMID- 21946406
TI  - Exercise assessment and training in pulmonary rehabilitation for patients with
      COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is a common condition with a growing
      impact on global health services. Patients with COPD frequently complain of
      dyspnoea and leg fatigue on exertion. Pulmonary rehabilitation (PR) is an
      established intervention for the management of patients with COPD. There is clear
      evidence for the benefit in this population. The purpose of this article is to
      describe the assessment process, exercise intervention and its anticipated
      benefits, in the context of a rehabilitation programme for individuals with COPD.
      This has been sub-divided into aerobic, skeletal muscle resistance and
      inspiratory muscle rationale, assessment and training. The evidence supporting
      the incorporation of aerobic and skeletal muscle resistance training in PR is
      well established. The benefit of including inspiratory muscle training (IMT) as
      an adjunct to PR is less clear.

PMID- 21946407
TI  - EJPRM systematic continuous Update on Cochrane reviews in rehabilitation: news
      from April 2011 to July 2011.
AB  - BACKGROUND: Since the number of publications about rehabilitation has been
      increasing over the years, there is necessity for reviews to have a more complete
      overlook of the evidence. The Cochrane Collaboration provides high quality
      reviews from which we can draw the most reliable clinical indications. Since 2007
      EJPRM lists and presents systematically all these reviews. AIM: The aim of the
      present paper was to systematically review all the new rehabilitation papers
      published from April 2011 up to July 2011 by the Cochrane Library in order to
      provide physicians involved in the field a summary with the best evidence
      nowadays available. METHODS: The authors systematically searched all the new
      papers of rehabilitative interest published from February 2, 2011 to April 22,
      2011 in the Cochrane Library. The retrieved papers have been then divided in
      subgroups according to their topic and the Cochrane Groups. RESULTS: The number
      of included papers was 8 (7 new reviews and 1 update review). A synthesis of
      abstracts is presented. CONCLUSION: The increased number of publication created a
      new need, the need of synthesising results to overcome conflicting evidence. The
      Cochrane Collaboration has been working on this aspect for many years, and its
      reviews, being systematic, are really relevant for professional update and to
      improve clinical practice. This article provides an overview of the most recent
      papers published in the Cochrane Library to help physiatrists and rehabilitation
      experts to be up to date.

PMID- 21946409
TI  - PubMed in progress: latest changes in MeSH and MyNCBI.
AB  - PubMed interface re-engineering has moved further steps with the latest changes
      in the MeSH - Medical Subject Headings database and in the MyNCBI homepage. Aim
      of this contribution is to present the most relevant added feature in order to
      improve your query efficiency.

PMID- 21946410
TI  - IGF1/insulin receptor kinase inhibition by BMS-536924 is better tolerated than
      alloxan-induced hypoinsulinemia and more effective than metformin in the
      treatment of experimental insulin-responsive breast cancer.
AB  - Epidemiologic and experimental evidence suggest that a subset of breast cancer is
      insulin responsive, but it is unclear whether safe and effective therapies that
      target the insulin receptor (IR), which is homologous to oncogenes of the
      tyrosine kinase class, can be developed. We demonstrate that both pharmacologic
      inhibition of IR family tyrosine kinase activity and insulin deficiency have anti
      neoplastic activity in a model of insulin-responsive breast cancer. Unexpectedly,
      in contrast to insulin deficiency, pharmacologic IR family inhibition does not
      lead to significant hyperglycemia and is well tolerated. We show that
      pharmacokinetic factors explain the tolerability of receptor inhibition relative
      to insulin deficiency, as the small molecule receptor kinase inhibitor BMS-536924
      does not accumulate in muscle at levels sufficient to block insulin-stimulated
      glucose uptake. Metformin, which lowers insulin levels only in settings of
      hyperinsulinemia, had minimal activity in this normoinsulinemic model. These
      findings highlight the importance of tissue-specific drug accumulation as a
      determinant of efficacy and toxicity of tyrosine kinase inhibitors and suggest
      that therapeutic targeting of the IR family for cancer treatment is practical.

PMID- 21946411
TI  - MiR-129-5p is required for histone deacetylase inhibitor-induced cell death in
      thyroid cancer cells.
AB  - The molecular mechanism responsible for the antitumor activity of histone
      deacetylase inhibitors (HDACi) remains elusive. As HDACi have been described to
      alter miRNA expression, the aim of this study was to characterize HDACi-induced
      miRNAs and to determine their functional importance in the induction of cell
      death alone or in combination with other cancer drugs. Two HDACi, trichostatin A
      and vorinostat, induced miR-129-5p overexpression, histone acetylation and cell
      death in BCPAP, TPC-1, 8505C, and CAL62 cell lines and in primary cultures of
      papillary thyroid cancer (PTC) cells. In addition, miR-129-5p alone was
      sufficient to induce cell death and knockdown experiments showed that expression
      of this miRNA was required for HDACi-induced cell death. Moreover, miR-129-5p
      accentuated the anti-proliferative effects of other cancer drugs such as
      etoposide or human alpha-lactalbumin made lethal for tumor cells (HAMLET). Taken
      together, our data show that miR-129-5p is involved in the antitumor activity of
      HDACi and highlight a miRNA-driven cell death mechanism.

PMID- 21946412
TI  - The profiles of red fluorescent proteins with antinucleopolyhedrovirus activity
      in races of the silkworm Bombyx mori.
AB  - Partially purified red fluorescent proteins (RFPs) secured from the gut juice of
      5th-instar multivoltine and bivoltine silkworm races were observed as several
      bands in electrophoretograms and chromatographic eluates. Interestingly,
      different races of silkworms had varying numbers of fluorescent protein bands: 11
      in Pure Mysore (resistant), 11 in Nistari (resistant), 4 in CSR(2) (moderately
      susceptible) and 1 in NB(4)D(2) (highly susceptible). Bioassay experiments
      indicated that the fluorescent bands had antinucleopolyhedrovirus (antiNPV)
      activity. The molar extinction coefficients and fluorescence quantum yields of
      all RFPs were estimated. The purified tetrapyrroles were characterized by UV
      visible absorption and fluorescence spectral analyses. All tetrapyrrole moieties
      associated with RFPs were found to be different and characteristic of the
      fluorescent bands. The resulting qualitative and quantitative differences among
      the individual RFPs from various races of silkworm were related to the
      susceptibilities of the silkworms to the viral disease. Moreover, light was found
      to be essential for the synthesis of RFPs, and, therefore, the role of light in
      the synthesis of RFPs was evaluated. Thus, this work may elucidate the process of
      RFP synthesis in silkworm, which may be used as a biomarker to measure the degree
      of susceptibility of silkworm races to NPV. Therefore, the characteristic band
      pattern may be used as an indicator to define the relative resistance of a race
      towards the specific virus.

PMID- 21946413
TI  - Inorganic polyphosphates are stored in spherites within the midgut of Anticarsia
      gemmatalis and play a role in copper detoxification.
AB  - Inorganic polyphosphates (PolyP) are widespread molecules that have been shown to
      play a role in metal detoxification and heavy-metal tolerance. In the present
      report, we investigated the functional role of spherites as PolyP-metal binding
      stores in epithelial cells of the midgut of Anticarsia gemmatalis, a lepidopteran
      pest of soybean. PolyP stores were detected by DAPI staining and indirect
      immunohistochemistry as vesicles distributed in columnar cells and around goblet
      cell cavities. These PolyP vesicles were identified as spherites by their
      elemental profile in cell lysates that were partially modulated by P- or V
      ATPases. PolyP levels along the midgut were detected using a recombinant
      exopolyphosphatase assay. When copper was added in the diet of larva, copper
      detection in spherites by X-ray microanalysis correlated with an increase in the
      relative phosphorous X-ray signal and with an increase in PolyP levels in
      epithelia cell lysate. Transmission electron microscopy of chemically fixed or
      cryofixed and freeze substituted tissues confirmed a preferential localization of
      spherites around the goblet cell cavity. Taken together, these results suggest
      that spherites store high levels of PolyP that are modulated during metal uptake
      and detoxification. The similarity between PolyP granules and spherites herein
      described also suggest that PolyP is one of the main phosphorous source of
      spherites found in different biological models. This suggests physiological roles
      played by spherites in the midgut of arthropods and mechanisms involved in heavy
      metal resistance among different insect genera.

PMID- 21946416
TI  - Pigment epithelium-derived factor (PEDF) protects cortical neurons in vitro from
      oxidant injury by activation of extracellular signal-regulated kinase (ERK) 1/2
      and induction of Bcl-2.
AB  - Mitigating oxidative stress-induced damage is critical to preserve neuronal
      function in diseased or injured brains. This study explores the mechanisms
      contributing to the neuroprotective effects of pigment epithelium-derived factor
      (PEDF) in cortical neurons. Cultured primary neurons are exposed to PEDF and H2O2
      as well as inhibitors of phosphoinositide-3 kinase (PI3K) or extracellular signal
      regulated kinase 1/2 (ERK1/2). Neuronal survival, cell death and levels of
      caspase 3, PEDF, phosphorylated ERK1/2, and Bcl-2 are measured. The data show
      cortical cultures release PEDF and that H2O2 treatment causes cell death,
      increases activated caspase 3 levels and decreases release of PEDF. Exogenous
      PEDF induces a dose-dependent increase in Bcl-2 expression and neuronal survival.
      Blocking Bcl-2 expression by siRNA reduced PEDF-induced increases in neuronal
      survival. Treating cortical cultures with PEDF 24 h before H2O2 exposure
      mitigates oxidant-induced decreases in neuronal survival, Bcl-2 expression, and
      phosphorylation of ERK1/2 and also reduces elevated caspase 3 level and activity.
      PEDF pretreatment effect on survival is blocked by inhibiting ERK or PI3K.
      However, only inhibition of ERK reduced the ability of PEDF to protect neurons
      from H2O2-induced Bcl-2 decrease and neuronal death. These data demonstrate PEDF
      mediated neuroprotection against oxidant injury is largely mediated via ERK1/2
      and Bcl-2 and suggest the utility of PEDF in preserving the viability of
      oxidatively challenged neurons.

PMID- 21946417
TI  - Innate lymphoid cells promote lung-tissue homeostasis after infection  with
      influenza virus.
AB  - Innate lymphoid cells (ILCs), a heterogeneous cell population, are critical in
      orchestrating immunity and inflammation in the intestine, but whether ILCs
      influence immune responses or tissue homeostasis at other mucosal sites remains
      poorly characterized. Here we identify a population of lung-resident ILCs in mice
      and humans that expressed the alloantigen Thy-1 (CD90), interleukin 2 (IL-2)
      receptor a-chain (CD25), IL-7 receptor a-chain (CD127) and the IL-33 receptor
      subunit T1-ST2. Notably, mouse ILCs accumulated in the lung after infection with
      influenza virus, and depletion of ILCs resulted in loss of airway epithelial
      integrity, diminished lung function and impaired airway remodeling. These defects
      were restored by administration of the lung ILC product amphiregulin.
      Collectively, our results demonstrate a critical role for lung ILCs in restoring
      airway epithelial integrity and tissue homeostasis after infection with influenza
      virus.

PMID- 21946418
TI  - Clinical research in cardiac rehabilitation and secondary prevention: looking
      back and moving forward.
AB  - Cardiac rehabilitation/secondary prevention (CR/SP) programs are considered
      standard of care and provide critically important resources for optimizing the
      care of cardiac patients. The objective of this article is to briefly review the
      evolution of CR/SP programs from a singular exercise intervention to its current,
      more comprehensive multifaceted approach. In addition, we offer perspective on
      critical concerns and suggest future research considerations to optimize the
      effectiveness and utilization of CR/SP program interventions.

PMID- 21946419
TI  - Effect of aerobic interval training on exercise capacity and metabolic risk
      factors in people with cardiometabolic disorders: a meta-analysis.
AB  - PURPOSE: To compare the effectiveness of high-intensity aerobic interval training
      (AIT) with active recovery and continuous moderate-intensity exercise (CME) on
      exercise capacity and metabolic risk factors in adults with cardiometabolic
      disorders through a systematic review and meta-analysis. METHODS: Studies were
      selected from 5 electronic databases (PubMed, MEDLINE, CINAHL, Physiotherapy
      Evidence Database [PEDro] and Cochrane Library Register of Controlled Trials).
      Randomized controlled trials (RCTs), published in English, that compared the
      effects of AIT with CME on exercise capacity and metabolic risk factors in adults
      with cardiometabolic disorders were included. Aerobic interval training was
      defined as high-intensity training separated by active recovery periods; CME
      incurred identical energy expenditure as AIT. Each trial was evaluated using the
      PEDro scale. Weighted mean difference (WMD) and 95% CIs were used to determine
      the effect size for each outcome. RESULTS: Six RCTs with 153 participants (40
      overweight/obesity, 19 with metabolic syndrome, and 94 with heart disease) were
      included. The mean value on the PEDro scale for these studies was 5.0. Aerobic
      interval training significantly increased peak oxygen consumption (WMD, 3.6
      mL.kg.min; 95% CI, 2.3-4.9) with a trend of decreasing fasting glucose (WMD, -0.4
      mmol/L; 95% CI, -0.9 to 0.2, P = .18) compared with CME. The effects on other
      metabolic risk factors were similar between AIT and CME. CONCLUSION: Analysis of
      a limited number of studies with small sample sizes indicates that AIT is
      superior to CME in terms of improving exercise capacity. Further high quality
      studies with larger sample size are required to confirm this finding in adults
      with cardiometabolic disorders.

PMID- 21946420
TI  - Cardiac rehabilitation outcomes: impact of comorbidities and age.
AB  - PURPOSE: Medical comorbidities (CM) contribute to cardiac rehabilitation (CR)
      underutilization. Whether individuals with coronary heart disease and an
      increased CM burden achieve similar benefits from CR as those with a low CM
      burden is unknown. METHODS: We analyzed 794 patients with coronary heart disease
      completing CR from 1/96 to 4/08. Medical CM burden was assessed using a
      comorbidity index (CMI) previously validated in a CR population. Distance
      achieved on a 6-minute walk test, body mass index, and the physical and mental
      component scores on the Medical Outcomes Short Form 36 were measured at baseline
      and at CR completion. We performed multivariable linear regression to compare
      changes in these parameters between individuals with a low CM burden (CMI = 0)
      and those with a moderate (CMI = 1-2) or high (CMI > 2) CM burden by age group
      (<56, 56-65, and >65 years of age). RESULTS: Mean age was 61.6 +/- 10.6 years,
      29% were women, 31% nonwhite; 305 individuals had a CMI = 0, 305 had a CMI = 1 to
      2, and 184 had a CMI > 2. All subgroups, regardless of age or CMI, demonstrated
      improvements with CR on virtually all parameters measured. Among individuals
      younger than 56 years, those with a CMI = 0 had greater improvements in these
      parameters after multivariable adjustment than those with a CMI of 1 to 2 or more
      than 2. In contrast, in older age groups, the degree of improvement was similar
      regardless of CMI. CONCLUSION: All patient groups, regardless of CM burden,
      benefited from CR. Medical CM burden, especially among older patients, should not
      discourage referral to CR.

PMID- 21946421
TI  - Aspirin for primary prevention of myocardial infarction: what is the evidence?
AB  - BACKGROUND: Aspirin has been advocated as a primary prevention measure for
      myocardial infarction (MI) for more than 2 decades. While several meta-analyses
      have supported this view, others have differed. All these analyses have focused
      on data from 6 major clinical trials. METHODS: We have provided a detailed
      analysis of the methods used in the individual trials (n = 6) included in the
      published meta-analyses. RESULTS: The major limitations of the meta-analyses
      relate to inclusion of heterogeneous trials characterized by widely differing
      study cohorts, absence of true control groups, lack of identification of silent
      MIs, failure to specify type of stroke, and inadequate information on management
      of conventional cardiac risk factors such as hypertension and hyperlipidemia.
      These issues preclude meaningful conclusions on the effects of aspirin in primary
      prevention of MI. CONCLUSIONS: This analysis does not support a general
      recommendation for the use of aspirin for primary prevention of MI and also
      suggests that effective management of risk factors in accordance with current
      guidelines may attenuate any potential benefit from aspirin with respect to MI.
      However, there may be a modest benefit in postmenopausal women with respect to
      stroke.

PMID- 21946422
TI  - [Epilepsy practice for neurologists].
AB  - Epilepsy is a common disease with a high incidence of about one percent.
      Knowledge of seizure semiology and correct reading of EEG findings are important
      for diagnosis of epilepsy. Because the primary therapy for epilepsy is
      antiepileptic drugs (AEDs), including several ones that are newly permitted in
      Japan, we need to prescribe them based on an understanding of their actions and
      interaction mechanisms. However, we also need to consider early surgical
      treatment for temporal lobe epilepsy with hippocampal sclerosis. In the
      therapeutic decision for adult epilepsy patients many factors such as employment,
      marriage, child bearing, and co-existent disease need to be considered. The
      present review provides an overview of the basis of epilepsy practice for
      neurologists treating adults with epilepsy, including a discussion of new AEDs,
      epilepsy surgery, women with epilepsy, and epilepsy in the elderly.

PMID- 21946423
TI  - [ABC in muscle pathology].
AB  - Muscle pathology plays a central role in the diagnosis of muscle diseases. Proper
      handling, fixation and transportation of muscle biopsy specimens are necessary to
      avoid artifacts. Hematoxylin and eosin provides information on basic
      morphological abnormalities, including general structural changes, fiber size
      variation, necrosis and regeneration, endomysial fibrosis and lymphocyte
      infiltration. Modified Gomori trichrome is useful to detect abnormal structures
      including protein aggregates. NADH-tetrazolium reductase highlights
      intermyofibrillar network, thus serving to detect myofibrillar disorganization.
      Myosin ATPase is used for evaluating fiber types. Selective type 1 fiber atrophy
      reflects myopathic process while fiber type grouping reinnervating process. The
      final interpretation whether the biopsy demonstrates myopathic or neuropathic
      changes is based upon all these findings.

PMID- 21946424
TI  - [A survey of cardiologists, diabetologists, gynecologists and ophthalmologists
      practicing in Osaka on the medical consultation behaviors of myotonic dystrophy
      patients].
AB  - An anonymous postal survey of cardiologists, diabetologists, gynecologists, and
      ophthalmologists in Osaka was performed to assess the medical care-seeking
      behaviors of and problems associated with the medical management of patients with
      myotonic dystrophy (DM). The questionnaires were sent to 927 cardiologists, 357
      diabetologists, 882 gynecologists, and 915 ophthalmologists. Of these, 172
      cardiologists, 85 diabetologists, 220 gynecologists, and 154 ophthalmologists
      responded. More than 30% of responders had provided care to DM patients, and
      approximately 10% had experience diagnosing DM patients. These facts suggest that
      DM patients receive medical care from various specialists due to complications
      involving multiple systems and some of them visit other specialists prior to
      neurologists. Some patients were diagnosed after perinatal or perioperative
      difficulties. Therefore, it seems important to improve the ability of physicians
      to identify DM patients. Because specialists with experience diagnosing DM paid
      more attention to the characteristic features of DM, such as grip myotonia and
      hatchet face, a simple screening test may be useful for detecting DM. Some
      responders pointed out the negative attitude of DM patients toward medical care
      and the lack of neurologists for consultation as problems in the medical
      management of DM patients. Cooperation among neurologists and other specialists
      and education of DM patients are important to improve the medical management of
      DM patients.

PMID- 21946425
TI  - [Dramatic improvement in two cases of anti-NMDA receptor encephalitis after
      immunomodulating therapy].
AB  - We report two patients with encephalitis associated with antibodies against NR1
      NR2 heteromers of the NMDA receptor that showed dramatic improvement after
      immunomodulating therapies. A 38-year old woman (case 1) suddenly developed
      seizures and short term memory loss. Brain MRI appeared almost normal except for
      a small number of high intensity spots of white matter on T(2) weighted images.
      Cerebrospinal fluid examination (CFS) disclosed lymphocytic pleocytosis (61/ul)
      and Qualitative analysis of NR1-NR2 antibodies in both CFS and serum were
      positive. Although an initial treatment with high-dose methylprednisolone was not
      beneficial for clinical improvement, intravenous immunoglobulin (IVIg) therapy
      led to complete recovery from her neurological problems. Repeated general surveys
      showed no evidence of tumors including ovarian teratoma. A 71-year old man (case
      2) suddenly developed seizures and short-term memory loss three days after
      receiving an influenza vaccination. Brain MRI appeared normal. CSF analysis
      revealed no pleocytosis and a slight elevation of protein value accompanying
      oligoclonal IgG band. Qualitative analysis of NR1-NR2 antibodies in both CFS and
      serum were positive. Intravenous high-dose methylprednisolone caused dramatic
      improvement and his neurological problems immediately disappeared. Repeated
      general surveys showed no evidence of tumors, as in case 1. These two cases
      showed relatively benign clinical courses with no evidence of tumors and were
      quite different from the well-known encephalitis associated with antibodies
      against NR1-NR2 heteromers of the NMDA receptor. Our clinical experience in these
      two cases suggests that the disease spectrum of anti-NMDA-receptor associated
      encephalitis might be broader than was once considered.

PMID- 21946426
TI  - [Diagnosis of pediatric multiple sclerosis initially presenting with tumefactive
      demyelinating lesion using 1H-magnetic resonance spectroscopy].
AB  - We report a case of tumefactive demyelinating lesion (TDL) diagnosed using (1)H
      magnetic resonance spectroscopy (1H-MRS) and conventional magnetic resonance
      imaging (MRI). A 7-year-old girl was admitted to our hospital with complaints of
      sleepiness and clumsiness of the right limbs. Neurological examination showed
      somnolence, right-sided apraxia, and hemiparesis with enhanced tendon reflexes
      and Babinski sign. Conventional brain MRI revealed extensive hyperintensity in
      the subcortical white matter of the left frontal lobe in both T2 weighted and
      fluid attenuated inversion recovery images. Gadolinium-enhanced T1 weighted
      images showed a tumor-like lesion in this area with interrupted rim enhancement,
      termed open ring sign, and a periventricular lesion along the inferior horn of
      the right lateral ventricle and a juxtacortical lesion under the right motor
      cortex. In 1H-MRS, both single voxel spectroscopy (SVS) and chemical shift
      imaging showed elevation of choline and reduction of N-acetylaspartate in the
      left frontal lobe lesion. Furthermore, SVS with a short echo time revealed
      elevated peaks for glutamate/glutamine complex in this lesion. These results
      suggested the demyelinating nature of this tumor-like lesion, in accordance with
      the concept of TDL. Based on this diagnosis, we treated the patient with three
      sets of methylprednisolone pulse therapy, which resulted in the reduction of TDL
      and neurological improvement. A follow-up study using MRI also demonstrated two
      more lesions in the corona radiata and internal capsule of the left hemisphere,
      supporting a diagnosis of multiple sclerosis based on the revised McDonald's
      criteria (2010). We concluded that 1H-MRS may be beneficial in the differential
      diagnosis of TDL.

PMID- 21946427
TI  - [A case of fasciitis localized in the calf muscles associated with Edwardsiella
      tarda sepsis].
AB  - A 49-year-old man presented with fever and pain, redness, swelling, and
      difficulty in walking. The serum C-reactive protein (CRP), creatin kinase (CK),
      and endotoxin levels were elevated. A blood culture revealed Edwardsiella
      tarda(E. tarda). Computed tomography (CT) showed subfascial and subcutaneous low
      density areas in the lower legs, suggesting focal abscesses and edema. The
      patient was likely to have necrotizing fasciitis or cellulitis. He was
      successfully treated with several antibiotics and discharged after 43 days.
      Because E. tarda causes sepsis and fulminating necrotizing fasciitis with a high
      mortality rate in patients with an underlying illness, it should be considered a
      potentially important pathogen. The lack of an underlying illness may be a factor
      for a good outcome in this case.

PMID- 21946428
TI  - [Two cases of posterior spinal artery syndrome (PSAS)].
AB  - We have reported two patients with posterior spinal artery syndrome. Both of them
      had sudden onset back pain, paraparesis, loss of deep sensation and bladder-bowel
      disturbances. MRI disclosed spinal cord lesions positioned at its posterior part
      including the posterior column or posterior horn at thoracic levels. Spinal
      artery syndrome is a rare disorder, especially the posterior spinal artery
      syndrome (PSAS). In our department, only ten patients had spinal artery syndrome
      out of 2,064 patients admitted to our hospital these 20 years. All the other 8
      patients had anterior spinal artery syndrome. It supports the notion that PSAS is
      rare. The detection rate of PSAS may increase after the routine use of spinal MRI
      in clinical practice. Our two patients had bilateral, symmetric symptoms. These
      symmetric signs and symptoms are usually seen in PSAS. The bilateral posterior
      spinal arteries connect with each other through many complex anastomoses.
      Moderate blood flow insufficiency may produce no clinical symptoms because of
      compensation by these anastomoses. When symptoms appear, these anastomoses do not
      compensate blood flow deficit and may produce bilateral symptoms.

PMID- 21946429
TI  - [A case of neuromyelitis optica with varicella zoster virus meningitis during
      mitoxantrone treatment].
AB  - A 36-year-old woman with neuromyelitis optica had been treated with steroids for
      the prevention of relapse. However, her treatment was not effective and she
      showed adverse effects such as diabetes mellitus, osteoporosis, compression
      fractures, and Pneumocystis carinii pneumonia. Therefore, we started her on
      mitoxantrone treatment. After five courses of mitoxantrone injection, she
      developed a herpes zoster infection in her thigh followed by aseptic meningitis.
      PCR for varicella zoster virus (VZV)-DNA was positive in the cerebrospinal fluid.
      The mechanisms that caused VZV reactivation by mitoxantrone are not known.
      Opportunistic herpes virus reactivation may occur easily with increasing use of
      immunosuppressive drugs for both neuromyelitis optica and multiple sclerosis.
      These drugs must be used under careful supervision.

PMID- 21946430
TI  - [Successful thrombectomy for basilar artery occlusion with Merci((r)) retrieval
      system: a case report].
AB  - A 66-year old hypertensive man having a prostate cancer was admitted to our
      hospital with sudden onset right hemiparesis. On admission, he showed left
      hemiplegia, hypesthesia, right limb ataxia, and dysarthria. The NIHSS score was
      16. Diffusion weighted magnetic resonance imaging showed an acute infarct in the
      middle pons and magnetic resonance angiography (MRA) revealed basilar artery (BA)
      occlusion. Carotid Doppler ultrasonography showed distal occlusion pattern of the
      bilateral vertebral artery. He was treated with intravenous rt-PA at 116 minutes
      after symptom onset. One hour later, his symptom was not improved and BA was
      still occluded on follow-up MRA. Therefore, we performed mechanical thrombectomy
      with Merci((r)) Retrieval System. At 323 minutes after onset, BA was successfully
      recanalized and NIHSS score decreased to 4 without hemorrhagic complication.
      Medication of oral warfarin was started on day 19 because paroxysmal atrial
      fibrillation was detected by electrocardiogram. The retrieved thrombus was
      pathologically diagnosed as a organizing mixed thrombus probable cardiac origin.
      On day 27, he was discharged home without any neurological deficit. Additional
      thrombectomy with Merci((r)) Retrieval System is a promising treatment strategy
      for BA occlusion which is resistant to intravenous rt-PA thrombolysis.

PMID- 21946432
TI  - Integrin alpha9beta1-mediated cell migration in glioblastoma via SSAT and Kir4.2
      potassium channel pathway.
AB  - The alpha9beta1 integrin accelerates cell migration through binding of the alpha9
      cytoplasmic domain to SSAT, which catalyzes the catabolism of higher order
      polyamines, spermidine and spermine, to the lower order polyamine, putrescine.
      SSAT levels were downregulated at both the mRNA and protein levels by shRNA
      mediated simultaneous knockdown of MMP-9 and uPAR/cathepsin B. In addition, we
      noted a prominent reduction in the expression of SSAT with MMP-9 and
      uPAR/cathepsin B knockdown in the tumor regions of 5310 injected nude mice
      brains. Further, SSAT knockdown in glioma xenograft cells significantly reduced
      their migration potential. Interestingly, MMP-9, uPAR and cathepsin B
      overexpression in these xenograft cells significantly elevated SSAT mRNA and
      protein levels. The migratory potential of MMP-9/uPAR/cathepsin B-overexpressed
      4910 and 5310 cells was not affected by either glybenclamide (Kir 6.x inhibitor)
      or tertiapin-Q (Kir 1.1 and 3.x inhibitor) but instead was significantly
      inhibited by either barium or Kir4.2 siRNA treatments. Co-localization of alpha9
      integrin with Kir4.2 was observed in both 4910 and 5310 xenograft cells. However,
      MMP-9 and uPAR/cathepsin B knockdown in these cells prominently reduced the co
      localization of alpha9 with Kir4.2. Taken together, our results clearly
      demonstrate that alpha9beta1 integrin-mediated cell migration utilizes SSAT and
      the Kir4.2 potassium channel pathway, and inhibition of the migratory potential
      of these glioma xenograft cells by simultaneous knockdown of MMP-9 and
      uPAR/cathepsin B could be attributed to the reduced SSAT levels and co
      localization of alpha9 integrin with Kir4.2 inward rectifier potassium channels.

PMID- 21946431
TI  - Functional significance of glycogen synthase kinase-3 regulation by serotonin.
AB  - Serotonin modulates brain physiology and behavior and has major roles in brain
      diseases involving abnormal mood and cognition. Enhancing brain serotonin has
      been found to regulate glycogen synthase Kinase-3 (GSK3), but the signaling
      mechanism and functional significance of this regulation remain to be determined.
      In this study, we tested the signaling mechanism mediating 5-HT1A receptor
      regulated GSK3 in the hippocampus. Using mutant GSK3 knock-in mice, we also
      tested the role of GSK3 in the behavioral effects of 5-HT1A receptors and the
      serotonin reuptake inhibitor fluoxetine. The results showed that activation of 5
      HT1A receptors by 8-hydroxy-N,N-dipropyl-2-aminotetralin (8-OH-DPAT) increased
      phosphorylation of the N-terminal serine of both GSK3alpha and GSK3beta in
      several areas of the hippocampus. The effect of 8-OH-DPAT was accompanied by an
      increase in the active phosphorylation of Akt, and was blocked by LY294002, an
      inhibitor of phosphoinositide 3-kinases (PI3K). Phosphorylation of GSK3beta, but
      not GSK3alpha, was necessary for 5-HT1A receptors to suppress the hippocampus
      associated contextual fear learning. Furthermore, acute fluoxetine treatment up
      regulated both phospho-Ser21-GSK3alpha and phospho-Ser9-GSK3beta in the
      hippocampus. Blocking phosphorylation of GSK3alpha and GSK3beta diminished the
      anti-immobility effect of fluoxetine treatment in the forced swim test, wherein
      the effect of GSK3beta was more prominent. These results together suggest that
      PI3K/Akt is a signaling mechanism mediating the GSK3-regulating effect of 5-HT1A
      receptors in the hippocampus, and regulation of GSK3 is an important intermediate
      signaling process in the behavioral functions of 5-HT1A receptors and fluoxetine.

PMID- 21946433
TI  - Activation of human fibroblast-like synoviocytes by uric acid crystals in
      rheumatoid arthritis.
AB  - Hyperuricemia-mediated uric acid crystal formation may cause joint inflammation
      and provoke the destruction of joints through the activation of inflammasome
      mediated innate immune responses. However, the immunopathological effects and
      underlying intracellular regulatory mechanisms of uric acid crystal-mediated
      activation of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA)
      have not been elucidated. Therefore, we investigated the in vitro effects of
      monosodium urate crystals, alone or in combination with the inflammatory
      cytokines tumor-necrosis factor (TNF)-alpha or interleukin (IL)-1beta, on the
      activation of human FLS from RA patients and normal control subjects and the
      underlying intracellular signaling mechanisms of treatment with these crystals.
      Monosodium urate crystals were able to significantly increase the release of the
      inflammatory cytokine IL-6, the chemokine CXCL8 and the matrix metalloproteinase
      (MMP)-1 from both normal and RA-FLS (all P<0.05). Moreover, the additive or
      synergistic effect on the release of IL-6, CXCL8 and MMP-1 from both normal and
      RA-FLS was observed following the combined treatment with monosodium urate
      crystals and TNF-alpha or IL-1beta. Further experiments showed that the release
      of the measured inflammatory cytokine, chemokine and MMP-1 stimulated by
      monosodium urate crystals were differentially regulated by the intracellular
      activation of extracellular signal-regulated kinase and c-Jun N-terminal kinase
      pathways but not the p38 mitogen-activated protein kinase pathway. Our results
      therefore provide a new insight into the uric acid crystal-activated
      immunopathological mechanisms mediated by distinct intracellular signal
      transduction pathways leading to joint inflammation in RA.

PMID- 21946434
TI  - A critical role of IL-17 in modulating the B-cell response during H5N1 influenza
      virus infection.
AB  - Interleukin-17 (IL-17), a member of the IL-17 cytokine family, plays a crucial
      role in mediating the immune response against extracellular bacteria and fungi in
      the lung. Although there is increasing evidence that IL-17 is involved in
      protective immunity against H1 and H3 influenza virus infections, little is known
      about the role of IL-17 in the highly pathogenic H5N1 influenza virus infection.
      In this study, we show that H5N1-infected IL-17 knockout (KO) mice exhibit
      markedly increased weight loss, more pronounced lung immunopathology and
      significantly reduced survival rates as compared with infected wild-type
      controls. Moreover, the frequency of B cells in the lung were substantially
      decreased in IL-17 KO mice after virus infection, which correlated with reduced
      CXCR5 expression in B cells and decreased CXCL13 production in the lung tissue of
      IL-17 KO mice. Consistent with this observation, B cells from IL-17 KO mice
      exhibited a significant reduction in chemokine-mediated migration in culture.
      Taken together, these findings demonstrate a critical role for IL-17 in mediating
      the recruitment of B cells to the site of pulmonary influenza virus infection in
      mice.

PMID- 21946436
TI  - The effects of ATP and sodium chloride on the cytochrome c-cardiolipin
      interaction: the contrasting behavior of the horse heart and yeast proteins.
AB  - In cells a portion of cytochrome c (cyt c) (15-20%) is tightly bound to
      cardiolipin (CL), one of the phospholipids constituting the mitochondrial
      membrane. The CL-bound protein, which has nonnative tertiary structure, altered
      heme pocket, and disrupted Fe(III)-M80 axial bond, is thought to play a role in
      the apoptotic process. This has attracted considerable interest in order to
      clarify the mechanisms governing the cyt c-CL interaction. Herein we have
      investigated the binding reaction of CL with the c-type cytochromes from horse
      heart and yeast. Although the two proteins possess a similar tertiary
      architecture, yeast cyt c displays lower stability and, contrary to the equine
      protein, it does not bind ATP and lacks pro-apoptotic activity. The study has
      been performed in the absence and in the presence of ATP and NaCl, two compounds
      that influence the (horse cyt c)-CL binding process and, thus, the pro-apoptotic
      activity of the protein. The two proteins behave differently: while CL
      interaction with horse cyt c is strongly influenced by the two effectors, no
      effect is observed for yeast cyt c. It is noteworthy that NaCl induces
      dissociation of the (horse cyt c)-CL complex but has no influence on that of
      yeast cyt c. The differences found for the two proteins highlight that specific
      structural factors, such as the different local structure conformation of the
      regions involved in the interactions with either CL or ATP, can significantly
      affect the behavior of cyt c in its reaction with liposomes and the subsequent
      pro-apoptotic action of the protein.

PMID- 21946435
TI  - Regulation of antiviral innate immunity by deubiquitinase CYLD.
AB  - An antiviral innate immune response involves induction of type I interferons
      (IFNs) and their subsequent autocrine and paracrine actions, but the underlying
      regulatory mechanisms are incompletely understood. Here we report that CYLD, a
      deubiquitinase that specifically digests lysine 63-linked ubiquitin chains, is
      required for antiviral host defense. Loss of CYLD renders mice considerably more
      susceptible to infection by vesicular stomatitis virus (VSV). Consistently, CYLD
      deficient dendritic cells are more sensitive to VSV infection. This functional
      defect was not due to lack of type I IFN production but rather because of
      attenuated IFN receptor signaling. In the absence of CYLD, IFN-beta is
      ineffective in the induction of antiviral genes and protection of cells from
      viral infection. These findings establish CYLD as a novel regulator of antiviral
      innate immunity and suggest a role for CYLD in regulating IFN receptor signaling.

PMID- 21946437
TI  - Conjugates of ferrocene with biological compounds. Coordination to gold complexes
      and antitumoral properties.
AB  - Several bioconjugates of ferrocene with biological compounds such as aminoacid
      esters and related species have been prepared by reaction of chlorocarbonyl
      ferrocene with the corresponding amino acid ester (histidine methyl ester,
      tryptophan methyl ester, methionine methyl ester and lysine ethyl ester) or
      histamine or prolinamide in the presence of NEt(3). The reaction of the
      tryptophan or prolinamide ferrocene conjugates with [Au(acac)(PR(3))]
      (acac=acetylacetonate) results in the substitution of the proton of the cyclic NH
      groups by the fragment AuPR(3)(+) affording the complexes [Au(FcCO-tryptophan
      OMe)(PR(3))] or [Au(FcCO-prolinamide)(PR(3))] (Fc=ferrocenyl group). The reaction
      of FcCO-Met-OMe with [Au(OTf)(PR(3))] (OTF=trifluoromethysulfonate) or
      [Au(C(6)F(5))(3)(OEt(2))] yields the gold(I) or gold(III) derivatives [Au(FcCO
      Met-OMe)(PR(3))]OTf or [Au(C(6)F(5))(3)(FcCO-Met-OMe)], respectively.
      Cytotoxicity studies towards several cancer lines such as MCF-7, HeLa or NIE-115
      have been performed. The ferrocene bioconjugates show no activity whereas the
      gold complexes exhibit antiproliferative effect. Preliminary studies of
      interaction of compounds with cells were carried out with the goal of increasing
      our knowledge on the mechanism of action of these potential drugs.

PMID- 21946438
TI  - Impact of functionalized coligands on the pharmacokinetics of 99mTcIII '4+1'
      mixed-ligand complexes conjugated to bombesin.
AB  - Bombesins (BN) containing (99m)Tc '4+1' complexes may be useful to detect tumors
      expressing the gastrin-releasing peptide receptor (GRPR). Derivatives of the
      formula [(99m)Tc(NS(3)R)(L2-BN(st))] were synthesized, in which Tc(III) is
      coordinated by an isocyanide L2-BN(st) bearing the peptide (BN(st)=betaAla
      betaAla-Gln-Trp-Ala-Val-Gly-His-Cha-Nle-NH(2)) and a tetradentate chelator
      NS(3)R. NS(3)R consists of 2,2',2"-nitrilotriethanethiol (NS(3)) bearing a crown
      ether (NS(3)crown), an aliphatic amine (NS(3)en) and a tricarboxylic acid
      (NS(3)(COOH)(3)). Non-radioactive Re compounds were prepared and analysed by
      electrospray ionization mass spectrometry. The structural similarity to the
      (99m)Tc conjugates was demonstrated by their identical HPLC elution profiles. The
      lipophilicity of [(99m)Tc(NS(3)R)(L2-BN(st))] decreased depending on the
      coligands NS(3)crown (log D(O/W), pH=7.4, 0.98 +/- 0.11), NS(3)en (-0.49 +/-
      0.07) and NS(3)(COOH)(3) (-2.01 +/- 0.09). Biodistribution in normal rats was
      characterized by an increasing kidney uptake and a decreasing uptake into the
      liver corresponding to the reduced lipophilicity of the conjugates. The
      pancreatic uptake expressed by the organ/blood ratio of standardized uptake
      values at 60 min p.i. in rats was 8.6 +/- 1.2 for [(99m)Tc(NS(3)en)(L2-BN(st))]
      and higher compared to the other conjugates. The pancreas/liver ratio of the SUV
      at 60 min p.i. in rats was highest for [(99m)Tc(NS(3)(COOH)(3))(L2-BN(st))] at
      8.4 +/- 1.3. [(99m)Tc(NS(3)en)(L2-BN(st))] was further studied in tumor-bearing
      mice and its pancreas/blood and pancreas/liver ratios were lower, however the
      pancreas/kidney ratios were higher in mice compared to rats. The activity uptake
      of [(99m)Tc(NS(3)en)(L2-BN(st))] into the PC-3 tumor xenografts was low (%ID/g:
      0.83 +/- 0.18 at 60 min; SUV: 0.21 +/- 0.05 at 60 min) but specific.

PMID- 21946439
TI  - Characterization and catechole oxidase activity of a family of copper complexes
      coordinated by tripodal pyrazole-based ligands.
AB  - A family of tripodal pyrazole-based ligands has been synthesized by a
      condensation reaction between 1-hydroxypyrazoles and aminoalcohols. The diversity
      was introduced both on the substituents of the pyrazole ring and on the side
      chain. The corresponding copper(II) complexes have been prepared by reaction with
      CuCl(2) in tetrahydrofuran. They have been characterized by EPR, UV spectroscopy
      and cyclic voltammetry. The absence of the half-field splitting signals in EPR
      suggests that the complex exists in solution as mononuclear species. The
      influence of substituents and side chain of the tripodal ligand on the
      catecholase activity of the complexes was studied. The reaction rate depends on
      two factors. First, the presence of an oxygen atom in the third position of the
      side chain should be avoided to keep the effectiveness of the reaction. Second,
      the electronic and steric effects of substituents on the pyrazole ring strongly
      affect the catalytic activity of the complex. Thus, best results were obtained
      with complexes containing unsubstituted pyrazole based-ligands. Kinetic
      investigations with the best catalyst based on the Michaelis-Menten model show
      that the catalytic activity of the mononuclear complex is close to that of some
      dicopper complexes described in literature.

PMID- 21946441
TI  - Return-to-sport outcomes at 2 to 7 years after anterior cruciate ligament
      reconstruction surgery.
AB  - BACKGROUND: Most people have not returned to their preinjury level of sports
      participation at 12 months after anterior cruciate ligament (ACL) reconstruction
      surgery. Twelve months' follow-up may be too early to assess return-to-sport
      outcomes accurately. PURPOSE: This study was undertaken to evaluate the medium
      term return-to-sport outcomes after ACL reconstruction surgery. STUDY DESIGN:
      Case series; Level of evidence, 3. METHODS: A self-report questionnaire was used
      to collect data at 2 to 7 years after ACL reconstruction surgery regarding
      preinjury sports participation, postoperative sports participation, and
      subjective knee function. The main inclusion criteria were participation in
      regular sports activity before injury and the attendance at routine surgical
      follow-up appointments. RESULTS: A total of 314 participants (mean age, 32.5 +/-
      10.2 years) were included at a mean 39.6 +/- 13.8 months after ACL reconstruction
      surgery. At follow-up, 45% were playing sport at their preinjury level and 29%
      were playing competitive sport. Ninety-three percent of the study sample had
      attempted sport at some time after their ACL reconstruction surgery. Those who
      had not attempted their preinjury level of sport by 12 months after surgery were
      just as likely to have returned to preinjury level by 39 months after surgery as
      those who had played sport by 12 months (risk ratio, 1.1; 95% confidence
      interval, 0.76-1.6). CONCLUSION: Less than 50% of the study sample had returned
      to playing sport at their preinjury level or returned to participating in
      competitive sport when surveyed at 2 to 7 years after ACL reconstruction surgery.
      Return to the preinjury level of sport at 12 months after surgery was not
      predictive of participation at the preinjury level in the medium term, which
      suggests that people who return to sport within 12 months may not maintain their
      sports participation.

PMID- 21946442
TI  - Epidemiology of traumatic spinal cord injuries in Iceland from 1975 to 2009.
AB  - STUDY DESIGN: Retrospective population-based epidemiological study. OBJECTIVES:
      To assess the nationwide, population-based incidence, causes, age, gender, extent
      and prevalence of spinal cord injuries (SCIs) in Iceland from 1975 to 2009.
      SETTING: Landspitali University Hospital in Iceland, the single referral center
      for SCIs in Iceland. METHODS: A retrospective review of hospital records on all
      admissions due to SCIs. Analysis of incidence, causes, age, gender, extent of
      injury and prevalence. RESULTS: A total of 207 patients with traumatic spinal
      cord injury (TSCI) were admitted: males 72%, females 28%. The percentage of
      females with TSCI increased to 37% in 2000-2004. Mean age at injury was 38 years.
      Average incidence per million population per year was 30 in 1975-1979, 12.5 in
      1995-1999 and 33.5 in 2005-2009. Thirty-day mortality was 6.3%. Causes of injury
      were road traffic accidents (RTA) in 42.5% of the cases; the majority did not use
      seatbelts. Falls amounted to 30.9%, with an increase of low falls among the
      elderly causing incomplete cervical lesions. Sport/leisure activities were the
      cause in 18.8%, of which 54% occurred after 2000. The main single cause of TSCI
      in sport/leisure were horse-riding accidents, followed by winter sport accidents,
      especially among women. Other causes constituted 7.7%. The injury was complete in
      39%; cervical lesions were 57% and thoracic/lumbar lesions were 43%. In December
      2009, the crude prevalence rate was 526 per million population. CONCLUSIONS: The
      findings showed a significant increase of TSCI in 2005-2009, especially in
      sport/leisure accidents and incomplete cervical lesions due to falls among
      elderly. Prevention strategies need to focus on these risk groups and on seatbelt
      use.

PMID- 21946443
TI  - Does spinal cord injury influence the mortality rate in patients with necrotizing
      fasciitis?
AB  - STUDY DESIGN: Retrospective chart review. OBJECTIVES: This study was performed to
      compare the outcome, especially the mortality rate, in patients with and without
      spinal cord injury (SCI) and necrotizing fasciitis (NF). SETTING: Division of
      Spinal Cord Injury and Department of Plastic and Hand Surgery, BG-University
      Hospital Bergmannsheil Bochum, Ruhr-University Bochum, Germany. METHODS: Twenty
      five patients with SCI and thirty patients without SCI treated with NF were
      included in the study. Mean length of hospital stay, mean age, mean laboratory
      risk indicator for necrotizing fasciitis (LRINEC) score, mean number of surgical
      debridements, co-morbidity factors and mortality rate were compared between both
      groups. RESULTS: There were no differences for the mean LRINEC score (P=0.07),
      mean number of surgical debridements (P=0.18) and co-morbidities (odds
      ratio=2.32; 95% confidence interval =0.78-6.92) between both groups. Patients
      with SCI were significantly younger than patients without SCI (P=0.02). Patients
      without SCI had a higher mortality risk rate (n=9) than patients with SCI (n=2)
      (relative risk=1.71; 95% confidence interval =1.13-2.6). CONCLUSIONS: In
      conclusion, SCI patients have a lower mortality rate than patients without SCI.
      Age may influence the mortality rate. Nevertheless, we believe that further
      unknown risk factors might influence the mortality, especially in patients with
      SCI.

PMID- 21946444
TI  - Natural course of life changes after spinal cord injury: a 35-year longitudinal
      study.
AB  - OBJECTIVES: To identify the natural course of changes in participation,
      employment, health and subjective quality of life over a 35-year interval among
      participants with spinal cord injury (SCI). METHODS: Participants were enrolled
      in 1973 from a specialty hospital in the Midwestern United States and assessed
      again approximately 35 years later. The inclusion criteria were the following:
      having traumatic SCI; being 18 years of age or older; and a minimum of 2 years
      having elapsed post injury. There were 64 participants who responded on both
      occasions. Average age at follow-up was 61.5 years, with 41.1 years having passed
      since SCI onset. The Life Situation Questionnaire was used to measure outcomes.
      RESULTS: Attrition analyses indicated that those who participated at follow-up
      were younger and had better overall outcomes at baseline (1973) when compared
      with those who dropped out of the study. Longitudinal analyses indicated a mixed
      pattern of favorable and unfavorable changes over the 35 years. The overall
      social participation decreased over time, although the sitting tolerance and
      hours spent in gainful employment increased. Non-routine physician visits
      increased. Satisfaction with employment improved over time, whereas satisfaction
      with social life, sex life and health declined. Self-reported adjustment
      improved, but the prediction of future adjustment in 5 years declined.
      CONCLUSION: Our study suggests that the natural course of SCI is marked by a
      survivor effect, whereby those with better outcomes are more likely to survive to
      follow-up, and a mixed pattern of favorable and unfavorable changes.
      Rehabilitation professionals should work to promote favorable outcomes in areas
      of strength, as well as minimize the likelihood of adverse outcomes.

PMID- 21946445
TI  - Efficacy of a new medical device based on colloidal silver and carbossimetyl beta
      glucan in treatment of upper airways disease in children.
AB  - AIM: Nasal congestion is the main symptom in common upper respiratory diseases in
      childhood. Intranasal administration of sympatheticomimetics decongestants is
      commonly adopted for this symptom. The Italian Drug Agency stated a warning
      against the use of these drugs in children under 12 years of age. The aim of this
      study is to evaluate the efficacy on nasal symptoms and the safety of a new
      medical device based on colloidal silver and carbossimetyl beta glucan compared
      with saline solution treatment in a group of children (0-12 years) affected by
      viral rhinitis. METHODS: Hundred consecutive outpatient children (0-12 year old),
      affected by common cold syndrome with evident nasal obstruction were randomly
      assigned to two type of intervention: group 1. receiving colloidal silver and
      carbossimetyl beta glucan; group 2. receiving saline solution. Each subject
      underwent clinical history and objective examination of rhinosinusal district at
      enrollment. Upper respiratory pathologie-related symptoms were specifically
      evaluated by using the Canadian Acute Respiratory Illness and Flu Scale (CARIFS).
      RESULTS: A significant improvement of CARIFS score was observed into the two
      groups. The score improvement of these two treatment was confirmed in all the age
      sub-group. We observed a statistically significant difference in mean post
      treatment CARIFS score and CARIFS globas VAS (Visual Analogic Scale) in children
      of group 1 compared with children in group 2 (2.28 +/- 1.58 vs. 5.08 +/- 3.39;
      P<0.001 and VAS: 1.87 +/- 1.38 vs. VAS: 3.34 +/- 2.19; P=0.012, respectively). At
      the end of treatment, 90% of subjects in group 1 resulted completely recovered,
      whereas 10% experienced some degree of complications (otitis, tracheitis,
      bronchitis). In group 2 a complete recovering was achieved in 66 % of subjects,
      the remaining 34 % developed complications. Tolerability profiles were similar in
      the two groups with no statistical differences in side effects in all age
      subgroups. CONCLUSION: Despite both treatments reached significative improvements
      in CARIFS global score and VAS and in physical examination of nasal mucosa and
      secretion at the end of the therapy, colloidal silver and carbossimetyl beta
      glucan showed a better performance with a significant difference in mean post
      treatment CARIFS global score and CARIFS VAS compared to treatment with saline
      solution.

PMID- 21946446
TI  - A comparative study on the effectiveness of two different devices in the
      management of developmental dysplasia of the hip in infants.
AB  - AIM: The aim of this paper was to compare the results of treatment of
      developmental dysplasia of the hip (DDH) with two different devices. METHODS: In
      118 DDH, authors employed, in a blinded randomized study, Teuffel-Mignon (TF) and
      Coxa-Flex (CF) devices. In this study checked 51 hips type IIC; 43 type IID; 15
      type IIIA; 9 type IIIB, by Graf classification. RESULTS: Hips Graf's type C were
      recovered in median 60.09 days, with TM in 50, with CF in 63,45; hips type D in
      100 days, with TM in 58,50, with CF in 89.00; hips type IIIA in 103.60 days, with
      TM in 122, with CF in 94.50; hips type IIIB in 108.66 days, with TM in 121, with
      CF in 102.50. CONCLUSION: The linear multiple regression model shows a
      statistically significant associations between outcome and pathological type (P
      value<0.001), age at diagnosis (P<0.001) and device (P<0.02). The statistical
      model shows that on average for each day of delay in the diagnosis is needed more
      than half a day for the patient to recover. The model confirmed that patients
      with more serious pathologies need more time to recover. Authors think that
      importance of the treatment of DDH isn't only the type of device employed, but a
      precise and correct sonographic diagnosis. Very important is starting the
      treatment as soon as possible, when the infant's bone of hip is more plastic and
      easy to treat. The authors' opinion is that employing a device instead of another
      isn't important, fundamental is the choice of the right device derived to a long
      time clinical experience.

PMID- 21946447
TI  - [Vaccination and celiac disease: results of a retrospective study].
AB  - AIM: Human leucocyte antigen (HLA) system plays an essential role in the human
      immune system activity and the expression of some specific HLA antigens could
      modify the immune response to vaccinations. Celiac disease is included among the
      diseases associated to specific HLA profiles, principally characterized by the
      expression of the HLA DQ2 antigen. METHODS: Our study was a retrospective study,
      leaded on a group of celiac children, with the object to evaluate their
      immunological response to both obligatory and recommended vaccinations in
      childhood. It was a retrospective study, including 66 patients affected by celiac
      disease, between 3 and 15 years of age, and a control group of 50 children of the
      same age. All patients performed both obligatory and recommended vaccinations as
      indicated in the Italian standard regimen for vaccinations. The immunologic
      response to each vaccine was analysed and compared in the two groups. Moreover,
      authors also studied the immunologic response to vaccines in celiac children
      comparing patients whose diagnosis was made before 18 months of age with those
      whose disease was diagnosed after 18 months of age. RESULTS: Our results showed
      that in celiac patients the immunological response to vaccine is similar to that
      one found in general population, except for HBV vaccine. CONCLUSION: The
      evaluation of immunological response to HBV vaccine should be regularly
      effectuated in celiac children and revaccination should be recommended.

PMID- 21946448
TI  - Incidence of urinary tract infection in neonates with septicemia: a prospective
      study.
AB  - AIM: The aim of this study was to investigate the incidence and clinical course
      of urinary tract infection (UTI) in neonates with septicemia and also determine
      the most common UTI manifestations in hospitalized neonates. METHODS: A cross
      sectional study was carried out on consecutive febrile infants aged 1 to 56 days
      that were hospitalized in the neonatal intensive care unit. In all neonates with
      positive urine culture, scintigraphy with technetium-99m-labeled
      dimercaptosuccinic acid (DMSA) and ultrasonography (US) were performed. Voiding
      cystourethrography was performed in the course of the illness, generally within 5
      7 days of hospitalization. RESULTS: Positive blood culture was detected only in
      9% of patients. However, 5% of them had positive urine culture. Positive abnormal
      US findings were present in two of five (40%) and vesicoureteral reflux (VUR) was
      present in one of five (20%) of infants with positive urine culture. CONCLUSION:
      DMSA scan revealed renal parenchymal abnormalities in 3 of 5 (60%) neonates with
      urosepsis. The incidence of UTI in neonates with septicemia is low. All neonates
      with sepsis and positive urine culture should undergo a screening renal
      scintigraphy and cystogram for identifying renal parenchymal involvement and
      urinary tract abnormalities.

PMID- 21946449
TI  - Outcomes and cardiac response of overweight prepubescent to the 6 minutes walk
      test.
AB  - The six-minute walk test (6-MWT) has proved to be clinically relevant to assess
      the ability to perform daily activities. This study aimed at examining the
      performance and the heart rate (HR) response of overweight/obese children to the
      6-MWT as compared their leaner pairs. Seventeen overweight children, aged 10.1+/
      0.8 yrs, were matched to 34 normal-weight children according to age, height, and
      gender. All children underwent anthropometry and performed a 6-MWT. Heart rate
      (HR) and blood pressure (BP) were recorded at rest, during, and after the test.
      Overweight children walked the same distance (623+/-107 m) when compared to their
      normal-weight pairs (611+/-67 m) (P=0.881). Nonetheless, the work granted in the
      6-MWT (i.e., 6 MWWk) was more important among overweight children (P<0.0001).
      Furthermore, only the 6 MWWk was correlated to the usual physical activity of
      children (r=-0.306 to -0.337, P<0.05). There was no difference in HR or its
      course during the test and in BP between overweight and normal-weight children.
      The 6-MWT elicits the HR of children at the same level and following an identical
      course regardless the weight status. Because of its relationships with the usual
      physical activity of children, the 6 MWWk needs to be considered as an important
      clinical outcome when the functional capacity of children is to be evaluated.
      There seems to be no contraindication to the 6-MWT among overweight/obese
      children free from any visible or declared orthopedic or musculoskeletal
      complications.

PMID- 21946450
TI  - Systolic and diastolic dysfunction in the intensive care unit.
AB  - Both systolic and diastolic dysfunction in the pediatric population can be
      identified by bedside echocardiography and can guide therapy and evaluate
      response to therapy. Isolated diastolic dysfunction is rare in children; however
      many conditions can lead to systolic dysfunction. In this review various
      echocardiographic techniques to evaluate both systolic and diastolic function as
      well as etiologies of systolic and diastolic dysfunction seen in the intensive
      care setting are discussed.

PMID- 21946451
TI  - Fluid management in critically ill pediatric patients with congenital heart
      disease.
AB  - Fluid balance management in pediatric critically ill patients is a challenging
      task, since fluid overload (FO) in the pediatric ICU is considered a trigger of
      multiple organ dysfunction. Pediatric patients with congenital heart disease
      (CHD) have several pre, intra and postoperative risk factors of derangements in
      fluid management. In particular, the smallest patients with acute kidney injury
      are at highest risk of developing severe interstitial edema, capillary leak
      syndrome and FO. Several studies previously showed a significantly higher
      percentage of FO among children with severe renal dysfunction requiring RRT,
      strongly associated with poor outcomes. For this reason, in children, priority
      indication is currently given to the correction of water overload. The present
      review will discuss recent literature addressing the issue of fluid balance in
      critically ill children with CHD, dosages, benefits and drawbacks of diuretic
      therapy, alternative diuretic/nephroprotective drugs currently proposed in the
      pediatric cardiac surgery setting. Monitoring of fluid balance will be reviewed.
      Specific modalities of pediatric extracorporeal fluid removal will be presented.

PMID- 21946452
TI  - Pediatric mechanical ventilation.
AB  - Mechanical ventilation has become a cornerstone of management of critically ill
      children in the intensive care unit. Indications for mechanical ventilation are
      numerous and strategies to effectively support patients yet minimize iatrogenic
      injury are imperative. This review aims to provide a broad overview of pediatric
      mechanical ventilation. A discussion of core principles of respiratory physiology
      integral to mechanical ventilation and an overview of commonly used ventilators
      and ventilator modes will be provided. Focus will then turn to general goals of
      mechanical ventilation with emphasis on pathophysiology. The latter half of the
      review will examine general indications for mechanical ventilation and mechanical
      ventilation in different disease states, including restrictive lung disease,
      obstructive lung disease, congenital heart disease, and shock. Finally,
      indications for and methods of weaning from mechanical ventilation will be
      discussed.

PMID- 21946453
TI  - [Early diagnosis of Fabry disease in children].
AB  - Fabry disease, a rare X-linked lysosomal storage disorder, is caused by
      deficiency of the enzyme alpha-galactosidase A. The incidence, ranging from one
      over 40 000 to one over 11 7000 worldwide is probably underestimated due to its
      unspecific pattern of presentation. The symptoms, including neurological,
      gastrointestinal, renal, ophthalmological and dermatologic manifestations, start
      in childhood and adolescence, cause a significant morbidity and are likely to
      affect the patient's quality of life. Furthermore, Anderson-Fabry disease always
      progress leading to a multiorgan dysfunction and life-threatening complications
      with end-stage renal disease, cardiomyopathy and high incidence of stroke. The
      estimated life in untreated patients is reduced by 15-20 years respectively in
      men and women. The enzyme replacement therapy, available in Europe from 2001,
      results in a reduction of major organs failure, morbidity and mortality. We
      present the case of an 8-year-old male admitted to our Division for overweight
      with a previous history of acroparesthesias, severe acute pain in hands and feet,
      abdominal pain, diarrhoea, constipation, bitemporal headache, dyshidrosis,
      recurrent fever, exercise intolerance and reduced quality of life. The physical
      examination was within normal limits. The alpha-galactosidase A activity was
      deficient in plasma and normal in peripheral leukocytes; the GLA gene showed a
      nucleotide substitution c.352C>T (p.Arg 118 Cys) in the eson 2 with a residual
      enzyme activity of the 29% suggesting the diagnosis of Fabry disease. Blood and
      urine chemistry, the slit-lamp examination and MRI of kidneys, heart and brain
      excluded any major organ involvement. The enzyme replacement therapy was then
      started almost three months ago using agasidase alfa at a dose of 0.2 mg/kg
      infused intravenously every two weeks but, unfortunately, no relief in the
      symptoms have been reported so far without any severe adverse reactions. This
      case report aims to point out the importance of an early diagnosis in order to
      prevent the progression of the disease, the multiorgan failure and to improve the
      long-term prognosis.

PMID- 21946454
TI  - [Craniofrontonasal syndrome: genetic aspects and description of a clinical case].
AB  - The authors describe the case of a child with craniofrontonasal syndrome (CFNS)
      (MIM 304110), the diagnostic process performed, the identification of the main
      clinical features in the proband (hypertelorism, facial asimmetry, bifid nasal
      tip, corpus callosum hypoplasia, broad thumb, curly and wiry hair), and the
      comparison with known data in literature. They also describe the detection,
      through gene sequencing of EFNB1, of responsible mutation and its correlation
      with the phenotypic variants. They explain the etiophatogenetic basis of the
      "unusual" inheritance pattern of CFNS: X-linked disease that occurs with greater
      severity in heterozygous females than hemizygous males. Finally, attention is
      placed on the need for careful genetic counseling for patients with CFNS, with
      special care in familial anamnesis taking. In the studied case, the presence of
      abnormalities of thumbs in the proband's mother and in two of her cousins,
      orientates principally toward a mutation of maternal origin or to a suspected
      somatic and germline mosaicism by creating a recurrence risk greater than general
      population. Because patients with CFNS reported in the literature are few, the AA
      consider that the observed case may help to improve understanding of the
      mechanisms of gene expression responsible for the syndrome, of its peculiar
      phenotypic manifestations and of its frequency in the population with known and
      easy to assign phenotypes, and possible mosaicisms that are difficult to detect.

PMID- 21946455
TI  - Extended starvation reduced and eliminated Wolbachia, but not Cardinium, from
      Metaseiulus occidentalis females (Acari: Phytoseiidae): a need to reassess
      Wolbachia's status in this predatory mite?
AB  - The presence of Wolbachia and Cardinium bacteria has been documented in many
      arthropod species, including the predatory mite Metaseiulus (=Typhlodromus or
      Galendomus) occidentalis (Nesbitt) (Acari: Phytoseiidae). We show that
      Tetranychus urticae, the prey of Metaseiulus occidentalis, contains Wolbachia and
      no detectable Cardinium using quantitative PCR (qPCR). Starvation for 72 h at 22
      degrees C eliminated most, if not all, Wolbachia in M. occidentalis adult females
      from 7 laboratory colonies. Refeeding of M. occidentalis with T. urticae after
      starvation for 72 h restored the amounts of Wolbachia in M. occidentalis to those
      of prestarvation levels, suggesting that Wolbachia detected in M. occidentalis
      starved for shorter periods of time in current, and some previous, studies likely
      came from T. urticae. Furthermore, eggs from all M. occidentalis colonies
      examined were free of Wolbachia if they were surface-decontaminated with 0.3%
      sodium hypochlorite before DNA extraction. Cardinium was present in 6 of 14
      laboratory colonies of M. occidentalis. Starvation for 3, 24, 48, and 72 h had no
      effect on the amounts of Cardinium in adult females from the Cardinium-positive
      colonies. Eggs from these colonies were positive for Cardinium but contained less
      than 1% of the titers found in adult females. The data suggest that Cardinium,
      but not Wolbachia, is an endosymbiont in certain populations of M. occidentalis.
      In light of our current findings, we recommend specific practices for the
      identification of potential symbionts in predatory arthropod species using the
      PCR.

PMID- 21946457
TI  - An audit of the variability of diagnosis and management of gout in the
      rheumatology setting: the gout evaluation and management study.
AB  - OBJECTIVE: The objectives of the study were to evaluate the rate of variability
      in diagnosis and treatment of the patients with gout in the rheumatology setting
      and to estimate the rate of adjustment to the European League Against Rheumatism
      recommendations as a key step to improve the quality of care in gout. METHODS:
      The GEMA (Gout Evaluation and MAnagement) study is a cross-sectional audit in
      which 803 files of patients with an International Classification of Diseases code
      of gout were randomly chosen from 41 rheumatology units. The data collected
      regarded the clinical management of gout. Indicators based on the European League
      Against Rheumatism recommendations were created, and information on the
      fulfillment of the recommendations was retrieved. The mean adjustment and 95%
      confidence interval (CI) were estimated for each recommendation. RESULTS:
      Patients from whose files information was retrieved were very representative of
      gout (94% were men, with a mean age of 60 years, 43% obese, 62% hypertensive,
      more than 25% with tophaceous gout, 61% hyperlipidemic). A diagnosis based on the
      observation of monosodium urate crystals on the microscope had been made in only
      26%; thus, the adjustment to diagnostic recommendations was low, 26.0% (95% CI,
      18.9%-33.1%). The adjustment to the recommendations on evaluating comorbidity was
      50.6% (95% CI, 46.6%-54.5%). Mean adjustment to recommendations on management, in
      general, was better, especially those regarding acute flares (100%), and
      lifestyle changes, with 71.4% (95% CI, 63.7%-79.1%) with treatment using urate
      lowering drugs could be improved (mean adjustment, 52.1% [95% CI, 43.1-61.1]).
      CONCLUSIONS: Overall, implementation of clinical care in gout should be put on
      further attention to diagnosis, time-consuming evaluation of comorbidities, and
      long-term control of serum urate levels.

PMID- 21946456
TI  - Fine structure analysis of black band disease (BBD) infected coral and coral
      exposed to the BBD toxins microcystin and sulfide.
AB  - Black band disease (BBD) of corals is a complex pathogenic polymicrobial mat
      community that lyses coral tissue as it migrates over an infected colony. Two
      known toxins are produced by BBD microorganisms - sulfide, produced by sulfate
      reducing bacteria, and microcystin, produced by cyanobacteria. Experiments were
      carried out to determine the effects of exposing healthy coral fragments to
      variable concentrations of purified microcystin, sulfide at a concentration known
      to exist in BBD, and a combination of the two. Healthy fragments of the coral
      Montastraea annularis were placed into experimental chambers with known toxin/s
      for 18-22.5 h. Fine structural analysis using scanning electron microscopy (SEM)
      showed that toxin exposure resulted in thinning or removal of the coral epidermal
      layer coupled with degradation of the gastrodermis. These effects were
      exacerbated when both toxins were used in combination. Exposure to sulfide and
      the highest concentration of microcystin caused zooxanthellae to dissociate from
      the coral tissue and to form clusters on the coral surface. Examination of coral
      fragments infected with BBD was carried out for comparison. It was determined
      that the effects of exposure to sulfide and microcystin on coral fine structure
      were consistent, both quantitatively and qualitatively, with the effects of
      artificially induced and naturally occurring BBD on M. annularis.

PMID- 21946458
TI  - Methotrexate pneumonitis in rheumatoid arthritis: increased prevalence with
      increasing latitude: an epidemiological study of trends in new zealand.
AB  - BACKGROUND: There is an association between increasing prevalence and increasing
      latitude for some autoimmune diseases, including rheumatoid arthritis (RA).
      Furthermore, in RA patients, a geographical variation in methotrexate pneumonitis
      has been suggested at a regional level in New Zealand. OBJECTIVE: The objective
      of the study was to determine if there is an increased incidence of methotrexate
      pneumonitis with increasing latitude in New Zealand. METHODS: A search was
      conducted using the NZ Ministry of Health's National Minimum Data Set for
      patients with discharge codes for RA (M05, M06) or history of RA and drug-induced
      lung disease (J702, J703, J704) or other (J189, J680, J90, J984) and methotrexate
      (Y431), for the period July 1, 1999, to June 30, 2008. Anonymous data were
      provided by the Ministry of Health for the 43 patients fulfilling these coding
      criteria and also the latitude and population of each domicile code. A Poisson
      regression analysis was undertaken with latitude as a continuous variable,
      adjusting for the total population at different latitudes. RESULTS: The incidence
      rate ratio for methotrexate pneumonitis shows a 16% increase per 1 degree of
      latitude (95% confidence interval, 7%-27%; P = 0.02). CONCLUSIONS: There was a
      latitudinal gradient seen in the rate of patient discharges for methotrexate
      pneumonitis, in the defined period. This supports the hypothesis that there is a
      latitude-dependent risk factor for this disorder and raises questions regarding
      possible environmental cofactors. It also supports the growing pool of evidence
      that certain immune-mediated conditions are more common at higher latitudes.

PMID- 21946459
TI  - Effects of anti-tumor necrosis factor agents for familial mediterranean fever
      patients with chronic arthritis and/or sacroiliitis who were resistant to
      colchicine treatment.
AB  - BACKGROUND: Effectiveness of anti-tumor necrosis factor (anti-TNF) agents in
      colchicine-resistant familial Mediterranean fever (FMF) patients has attracted
      attention in recent years. OBJECTIVE: We analyzed the effect of anti-TNF agents
      on clinical findings of colchicine-resistant FMF patients with chronic arthritis
      and/or sacroiliitis. METHODS: Data from 10 FMF patients (5 male and 5 female
      patients: mean age, 30.1 [SD, 8.5] years) with chronic arthritis and/or
      sacroiliitis who were on anti-TNF agents are reviewed. Frequency of FMF attacks
      before and after treatment with anti-TNF agents was recorded from hospital files.
      The effects of the anti-TNF treatment were determined by using the number of
      tender and/or swollen joints, serum acute phase reactant levels, and Bath
      Ankylosing Spondylitis Disease Activity Index scores. Change in urine protein
      loss was also evaluated in patients with amyloidosis. In 6 patients, FMF attacks
      had been considered to be unresponsive to colchicine, and 4 patients were partial
      responders before treatment with anti-TNF agents. RESULTS: Mean attack frequency
      of the patients in the 3 months' period before anti-TNF agent treatment was 3.8
      (SD, 3.1). After anti-TNF treatment, in 3 patients, FMF attack frequency
      decreased, and in the remaining 7 patients, no attack occurred. Serum acute phase
      reactant levels were decreased significantly at 3 and 6 months after anti-TNF
      treatment (P < 0.05 for all). After anti-TNF treatment Bath Ankylosing
      Spondylitis Disease Activity Index scores were also decreased significantly (6.2
      [SD], 1.7 vs. 2.1 [SD], 1.7; P = 0.012). In all 3 patients with amyloidosis,
      urine protein loss decreased without any increase in serum creatinine levels.
      CONCLUSION: Anti-TNF treatment can have beneficial effects for controlling FMF
      attacks in FMF patients with chronic arthritis and/or sacroiliitis.

PMID- 21946460
TI  - Tenosynovitis caused by a pseudallescheria boydii infection and symptoms of
      reflex sympathetic dystrophy after a dog bite.
AB  - Tenosynovitis caused by a Pseudallescheria boydii infection is an extremely rare
      complication after a dog bite and is easily misdiagnosed, leading to a delay in
      treatment. Careful history taking and adequate cultures can lead to a timely
      diagnosis, and longstanding antimycotic treatment can successfully eradicate the
      fungus.

PMID- 21946461
TI  - Acute symptomatic intervertebral disk calcification in a child with
      retropharyngeal edema: computed tomography and magnetic resonance findings.
AB  - Intervertebral disk calcification in children is an uncommon self-limiting
      disease, which can cause symptoms like neck pain or torticollis, and can be
      treated with conservative management. The calcified disk material can herniate
      anteriorly, inducing dysphagia, or herniate posteriorly, causing neurologic
      symptoms secondary to spinal cord compression. We report computed tomography and
      magnetic resonance findings of a symptomatic intervertebral disk calcification at
      the C2-3 level with retropharyngeal edema caused by anterior herniation of
      calcified material in a 7-year-old boy.

PMID- 21946462
TI  - Primary sjogren syndrome manifested as localized cutaneous nodular amyloidosis.
AB  - Localized cutaneous nodular amyloidosis (LCNA) is the rarest type of cutaneous
      amyloidosis. Typically presenting as waxy nodules on the lower extremities, it
      demonstrates localized deposition of AL-type amyloid in immunohistologic study
      and is often associated with focal plasma cell proliferation. Sjogren syndrome,
      an autoimmune lymphoproliferative disorder, is characterized by
      keratoconjunctivitis sicca and xerostomia with lymphocytic infiltration of
      exocrine glands. As shown in case reports, the association of LCNA with Sjogren
      syndrome is considerable. Herein, we report a 78-year-old woman with LCNA, who
      was further surveyed and diagnosed with Sjogren syndrome. In light of the
      significant relation between these 2 diseases, further examination for
      coexistence of Sjogren syndrome in addition to systemic amyloidosis is well
      warranted. Prompt identification of an underlying Sjogren syndrome in LCNA with
      polyclonal immunoglobulin amyloid may have important therapeutic consequences.

PMID- 21946463
TI  - Raynaud phenomenon of the nipple: a rare finding in rheumatology clinic.
AB  - Many clinicians are familiar with the common presentation of Raynaud phenomenon
      affecting the hands and feet. Patients with Raynaud phenomenon, even in the
      absence of systemic disease, are frequently treated by rheumatologists. Raynaud
      phenomenon of the nipple is an important entity to recognize as a cause of severe
      nipple pain with breast-feeding and is perhaps underrecognized by patients and
      physicians. We describe a patient with Raynaud phenomenon of the nipple to
      improve identification of this clinical entity so that appropriate treatment may
      be instituted, thus allowing mothers to continue nursing.

PMID- 21946464
TI  - Clarithromycin in adult-onset still's disease: a potentially useful therapeutic.
AB  - Adult-onset Still's disease (AOSD), an autoinflammatory syndrome of unknown
      etiology, typically manifests with spiking fevers, polyarthritis, and
      characteristic evanescent rash. We describe a young woman with AOSD complicated
      by calf fasciitis that serendipitously responded to clarithromycin administered
      for another indication. Remarkable improvement followed rechallenges with
      clarithromycin for subsequent AOSD flares. In addition to their antibacterial
      actions, macrolides demonstrate immunomodulatory effects, including suppression
      of proinflammatory cytokine production and neutrophil action. Previous clinical
      trials provide promising preliminary evidence of a therapeutic effect of
      macrolides in chronic inflammatory diseases. Although AOSD pathogenesis remains
      unclear, a role for dysregulation of innate immunity is supported by recent
      literature. Based on this possible innate immune mechanism, we suspect that
      macrolides may have induced a therapeutic response in this patient with AOSD. A
      clinical trial is warranted to establish or refute their therapeutic efficacy.

PMID- 21946465
TI  - Successful use of tocilizumab in a patient with rheumatoid arthritis following
      severe pancytopenia during etanercept therapy.
AB  - Severe cytopenia, including neutropenia and anemia, may occasionally occur during
      anti-tumor necrosis factor alpha (TNF-alpha) therapy. However, its mechanism is
      poorly understood, and little is known concerning the rationale of the choice of
      biologic therapy after a severe episode of cytopenia. The authors present the
      case of a 68-year-old rheumatoid arthritis patient in whom severe pancytopenia
      developed soon after the initiation of etanercept therapy. After resolution, the
      interleukin 6 receptor-blocking agent tocilizumab was introduced, which resulted
      in long-lasting complete remission of the rheumatoid arthritis without any
      adverse effects. The apoptosis-inducing effects of 3 TNF-alpha blockers and
      tocilizumab on peripheral blood mononuclear cells of the patient were compared by
      means of annexin V and propidium iodide labeling and flow cytometry. In concert
      with the clinical events, the anti-TNF-alpha agents demonstrated significantly
      higher apoptotic activities than that of tocilizumab. Tocilizumab appeared safe
      after anti-TNF-alpha-induced cytopenia possibly caused by apoptosis induction.

PMID- 21946466
TI  - Invasive polyarticular septic arthritis caused by nontypeable haemophilus
      influenzae in a young adult: a case report and literature review.
AB  - Nontypeable Haemophilus influenzae is a rare cause of septic arthritis in adults
      and has been reported to be associated with underlying medical conditions. We
      present a case of nontypeable H. influenzae-infected severe invasive
      polyarticular septic arthritis in a young adult without any underlying
      predisposing medical conditions. Diagnosis was made from both positive blood
      culture and joint aspiration culture. The patient was successfully treated with
      employment of aggressive surgical debridement of multiple affected septic joints
      as well as prolonged antibiotic treatment. Further laboratory testing did not
      reveal significant underlying medical conditions including negative HIV, normal
      levels of complement and IgG subclasses, and normal-appearing spleen on computed
      tomography. This case illustrates that nontypeable H. influenzae can cause
      serious invasive septic arthritis infection in both patients with and without
      predisposing underlying medical conditions and that prompt diagnosis with
      aggressive treatment of combined surgical and medical treatment can result in
      optimal recovery.

PMID- 21946467
TI  - Hemorrhagic bullae of the oral mucosa as an early manifestation of vascular-type
      ehlers-danlos syndrome.

PMID- 21946468
TI  - Exacerbation of infliximab-induced palmoplantar psoriasis under ustekinumab
      therapy in a patient with ankylosing spondylitis.

PMID- 21946469
TI  - Catastrophic axial gout causing paraplegia in a patient with glycogen storage
      disease.

PMID- 21946470
TI  - Impact of deficits in gout care on hospitalizations.

PMID- 21946471
TI  - Risk factors for the recurrence of IgG4-related Sclerosing disease without
      autoimmune pancreatitis.

PMID- 21946472
TI  - Physical activity and screen time: trends in U.S. children aged 9-13 years, 2002
      2006.
AB  - BACKGROUND: We examined trends of physical activity and screen time among
      nationally representative samples of children aged 9-13 years to explore whether
      children overall are becoming less physically active and less likely to be in
      compliance with screen time recommendations. METHODS: We analyzed Youth Media
      Campaign Longitudinal Survey data for trends and demographic patterns of free
      time and organized physical activity, and hours and minutes of watching
      television and playing video or computer games. Child-parent dyads for 2002 (N =
      3114), 2004 (N = 5177), and 2006 (N = 1200) were analyzed. RESULTS: On the day
      before the interview, and for free time physical activity in the past week,
      children reported a significant increase in physical activity from 2002-2006.
      Screen time levels were stable overall; 76.4% of children met the recommendations
      of 2 hours or less of daily screen time. CONCLUSION: Levels of physical activity
      among U.S. children aged 9-13 years were stable, or levels slightly improved from
      2002-2006. Except for some subgroup differences, trends for compliance with
      screen time recommendations were also stable from 2002-2006 for U.S. children
      aged 9-13 years.

PMID- 21946473
TI  - Study of the critical points and the role of the pores and viscosity in
      carbamazepine hydrophilic matrix tablets.
AB  - Percolation theory has been applied to estimate the Hypromellose (HPMC)
      percolation thresholds and the influence of the polymer viscosity and the initial
      porosity on these thresholds in carbamazepine multicomponent matrix formulations.
      Different batches containing two viscosity grades of HPMC as hydrophilic matrix
      forming polymer, MCC and lactose as fillers, and a lubricant mixture have been
      manufactured varying the compression pressure in order to obtain matrices with
      three levels of initial porosity. The results suggested the existence of an
      excipient percolation threshold between 13 and 15% v/v of HPMC for the different
      batches prepared. It has been found that the percolation threshold for this
      polymer is independent on the formulation factors studied in this paper: polymer
      viscosity and initial porosity of the matrices.

PMID- 21946475
TI  - Knowledge and practice outcomes after home blood pressure measurement education
      programs.
AB  - OBJECTIVES: We investigated the outcomes of three home blood pressure measurement
      (HBPM) education programs on adult knowledge and practice. METHODS: We chose a
      pretest/post-test design and randomly divided 95 adults into three groups:
      individual training (group A), group training (group B), and self-learning (group
      C), for education regarding HBPM in accordance with the Canadian Hypertension
      Education Program. Participants involved in groups A and B received interactive
      education led by a nurse. Participants in group C learned by themselves using an
      instruction booklet and a HBPM device lent to them for 7 days. Knowledge was
      assessed pretest and post-test by questionnaire. Skills were evaluated
      postintervention by direct observation. RESULTS: Analysis of the 60 participants
      indicated significant knowledge improvement. Pretest scores of 38 (group A), 54
      (group B), and 45% (group C) rose significantly to 97, 99, and 90%, respectively
      (pretest vs. post-test; P<0.0001). Individual and group training sessions were
      significantly more effective compared with the self-learning program, which was
      confirmed by differences between groups in post-test practice. Assessment scores:
      74 (group A), 79 (group B), and 53% (group C; group A vs. group C; P=0.001, group
      B vs. group C; P=0.001). CONCLUSION: Our findings indicate that adults attending
      an individual or group training program for HBPM retained its theoretical and
      practical principles better than those engaged in self-learning. Their success
      may be attributed to interaction with the nurse.

PMID- 21946474
TI  - A protocol for the classification of powder compression characteristics.
AB  - In this paper, a structured protocol for powder compression analysis as a test to
      assess the mechanical properties of particles in a formulation development
      programme is presented. First, the sequence of classification steps of the
      protocol is described, and secondly, the protocol is illustrated using
      compression data of six powders of two model substances, sodium chloride and
      mannitol. From powder compression data, a set of compression variables are
      derived, and by using critical values of these variables, the stages expressed
      during the compression of the powders are identified and the powders are
      classified into groups with respect to the expression of particle rearrangement,
      particle fragmentation and particle plastic deformation during compression. It is
      concluded that the proposed protocol could, in a satisfactorily way, describe and
      distinguish between the powders regarding their compression behaviour. Hence, the
      protocol could be a valuable tool for the formulation scientist to
      comprehensively assess important functionality-related characteristics of drugs
      and excipients.

PMID- 21946476
TI  - The sealing ability of a new silicone-based root canal filling material
      (GuttaFlow): an in vitro study using the percentage of gutta-percha-filled area.
AB  - Percentage of gutta-percha-filled area (PGFA) was used to investigate the sealing
      ability of GuttaFlow. A total of 80 mandibular first premolars with single canal
      were randomly divided into 4 Groups (n=20) according to root canal filling
      technique and/or material - Group1: cold lateral condensation technique; Group 2:
      continuous wave condensation technique; Group 3: GuttaFlow; Group 4: GuttaFlow
      and accessory gutta-percha cones without lateral condensation. The PGFA values of
      Groups 3 and 4 were significantly higher than those of Groups 1 and 2 (p<0.05),
      but there were no significant differences between Group 3 and Group 4 (p>0.05).
      It was concluded that GuttaFlow provided superior sealing ability, such that
      accessory gutta-percha cones became unnecessary when filling root canals with
      GuttaFlow.

PMID- 21946477
TI  - Effect of functional monomers in all-in-one adhesive systems on formation of
      enamel/dentin acid-base resistant zone.
AB  - This study aimed at evaluating the effect of functional monomers in all-in-one
      adhesive systems on formation of acid-base resistant zone (ABRZ) in enamel and
      dentin. Experimental adhesive systems containing one of three functional
      monomers; MDP, 3D-SR and 4-META were applied to enamel or dentin surface and
      light-cured. A universal resin composite was then placed. The specimens were
      subjected to a demineralizing solution (pH 4.5) and 5% NaClO for acid-base
      challenge and then observed by SEM. The ABRZ was clearly observed in both enamel
      and dentin interfaces. However, enamel ABRZ was thinner than dentin ABRZ in all
      adhesives. Morphology of the ABRZ was different between enamel and dentin, and
      also among the adhesives. Funnel-shaped erosion was observed only in the enamel
      specimen with the 4-META adhesive. The formation of enamel/dentin ABRZ was
      confirmed in all adhesives, but the morphology was influenced by the functional
      monomers.

PMID- 21946478
TI  - Histopathological and immunohistochemical study on the effects of a direct pulp
      capping experimentally developed adhesive resin system containing reparative
      dentin-promoting agents.
AB  - The studies so far conducted by our colleagues in relation to dental pulp capping
      using adhesive resins revealed that the adhesive resins are useful for capping
      exposed pulps but are a little slower to take effect on the injured pulp tissue
      during the initial stage: up to 90-days after pulp exposure, compared with
      calcium hydroxide and its preparations. In the present study, an experimentally
      developed adhesive resin system was applied in direct pulp capping and
      restoration and the healing process was examined histopathologically and
      immunohistochemically. The resin system was manufactured with calcium phosphate
      added into the bonding material for the purpose of accelerating the healing
      process. The largest amount of reparative dentin was formed by SE5 (whitlockite 5
      wt%), followed by SE9 (hydroxyapatite 5 wt%, whitlockite 5 wt%), SE1
      (hydroxyapatite 5 wt%), and SE2 (hydroxyapatite 10 wt%). Generally, it could be
      said that the experimental groups using whitlockite and hydroxyapatite had the
      tendency to produce a larger amount of reparative dentin.

PMID- 21946479
TI  - Ion release from metal-ceramic alloys in three different media.
AB  - The aim of this in vitro study was to assess the effect of pH changes on ion
      release of metal-ceramic dental casting alloys. Samples from four commercially
      available alloys (Wirobond C, Wiron 99, Rematitan CP-Ti grade 1, and PontoStar)
      were prepared and polished. Ion release of alloys subjected to three different pH
      media (artificial saliva of pH 2.3, pH 6.5 and 0.9% saline solution of pH 7.3)
      for periods of 7, 15, 30, and 60 days were assessed by means of atomic absorption
      spectroscopy. Microscopic changes on surfaces of metallic samples before and
      after immersion were compared by scanning electron microscopy. ANOVA was used for
      statistical analysis of results. For all ions, pH and period interactions were
      statistically significant: highest amount of ion release occurred after 60 days
      of immersion regardless of pH value. For every alloy, ion release results were
      highest in artificial saliva of pH 2.3 and lowest in 0.9% saline solution. It was
      concluded that ion release from alloys was pH-dependent.

PMID- 21946480
TI  - Soda-lime glass as a binder in reusable experimental investment for dental
      castings.
AB  - In this study, different glasses were investigated to improve reusable
      investments. Borosilicate glass (BSG) powder and soda-lime glass (SLG) powder
      were prepared by milling broken beakers and microscope slides, respectively, and
      used in experimental investments (I-BSG, I-SLG) by blending glass powder (10 wt%)
      with cristobalite (90 wt%). Some properties and casting fits were evaluated with
      commercial gypsum-bonded investment as the control. Both BSG and SLG were mainly
      composed of Si, but SLG had a large Ca content. The glass transition temperatures
      were approximately 800 degrees C (BSG) and 700 degrees C (SLG). Experimental
      investments with heating showed the significantly (p<0.05) higher expansion than
      that of the control. The compressive strength of I-SLG was higher than that of I
      BSG, and increased with temperature. The MOD inlay obtained from I-SLG had a
      significantly smaller gap than that from I-BSG, and was comparable to the
      control. These results suggest SLG could be applied clinically as a reusable
      dental investment.

PMID- 21946481
TI  - Effects of a newly designed HEMA-free, multi-purpose, single-bottle, self-etching
      adhesive on bonding to dental hard tissues, zirconia-based ceramics, and gold
      alloy.
AB  - This study investigated the bonding effectiveness of newly designed self-etching
      adhesives to four types of adherends--enamel, dentin, zirconia, and gold (Au)
      alloy. Five experimental adhesives were prepared, which contained 3.0-5.0 wt% 6
      methacryloyloxyhexyl phosphonoacetate (6-MHPA) or 6-methacryloyloxyhexyl 3
      phosphonopropionate (6-MHPP), 3.0 wt% 4-acryloyloxyethoxycarbonylphthalic acid (4
      AET) or 17.0 wt% 4-methacryloyloxyethoxycarbonylphthalic acid (4-MET), 0-0.5 wt%
      6-methacryloyloxyhexyl 6,8-dithiooctanoate (6-MHDT) or 10-methacryloyloxydecyl
      6,8-dithiooctanoate (10-MDDT), and varying contents of Bis-GMA, dimethacrylate
      monomers, water, acetone, and a photoinitiator system. After 2,000 times of
      thermal cycling, shear bond strengths (SBSs) between a resin composite (Beautifil
      II, Shofu Inc., Japan) and the four adherends, bonded using the experimental
      adhesives, were measured at 1.0 mm/min. No statistically significant differences
      in SBS for bonding to ground enamel, dentin, sandblasted zirconia and Au alloy
      (p>0.05) were found between experimental adhesives which contained 6-MHPA and/or
      6-MHPP, 4-MET or 4-AET, 6-MHDT and/or 10-MDDT, Bis-GMA, and dimethacrylates. An
      adhesive layer of less than 5.0 um thickness, by scanning electron microscopy
      observation, revealed strong adhesion to the four adherends. Therefore, the newly
      designed multi-purpose, self-etching adhesive strongly adhered to all the four
      adherend materials tested.

PMID- 21946482
TI  - Optimum design for glass fiber-reinforced composite clasps using nonlinear finite
      element analysis.
AB  - The purpose of this study was to design an optimum glass fiber-reinforced
      composite (FRC) clasp. Three-dimensional finite element models were constructed
      of FRC circumferential clasp arms and an abutment tooth. The basic clasp arm was
      half-oval, without a taper, 2.60 mm wide and 1.30 mm thick. Four modified clasp
      arms were prepared by changing the width or thickness of the basic clasp
      (width/thickness: 2.60 mm/0.65 mm, 2.60 mm/1.95 mm, 1.30 mm/1.30 mm, and 3.90
      mm/1.30 mm). Forced displacements of 5 mm in the removal direction were applied
      to the nodes at the base of the clasp arm. The retentive forces and maximum
      tensile stresses of the five FRC clasp arms ranged from 1.00-16.30 N and from
      58.9-151 MPa, respectively. Results showed that an optimum FRC clasp was a
      circumferential clasp with 2.60 mm width and 1.30 mm thickness, which had
      sufficient retentive force and low risk of tensile failure.

PMID- 21946483
TI  - Effects of surface roughness and tapered angle of cone crown telescopic system on
      retentive force.
AB  - This study evaluated the effect of surface roughness and tapered angle of cone
      crowns on retentive force (RF). Cone crowns from Ti-6Al-7Nb alloy with a tapered
      angle of 4, 5, or 6 degrees  were fabricated using a milling machine and a
      finishing machine to produce a smooth surface. Cone crowns of 6 degrees  with a
      rough surface were also prepared. The RF during 1,000 cycles of
      insertion/separation was recorded. The first RF of the 6 degrees  cone crowns was
      24.2-27.7 N, and the surface roughness was not significant. The RF of all
      specimens decreased at 100 cycles, then those of inner and outer crowns with the
      same roughness remained unchanged, but those of different roughnesses increased
      with number of cycles. The RF of cone crowns with a smaller tapered angle was
      significantly greater than with a larger angle at any measured cycles.

PMID- 21946484
TI  - The use of easily debondable orthodontic adhesives with ceramic brackets.
AB  - We experimentally produced an easily debondable orthodontic adhesive (EDA)
      containing heat-expandable microcapsules. The purpose of this in vitro study was
      to evaluate the best debondable condition when EDA was used for ceramic brackets.
      Shear bond strengths were measured before and after heating and were compared
      statistically. Temperatures of the bracket base and pulp wall were also examined
      during heating. Bond strengths of EDA containing 30 wt% and 40 wt% heat
      expandable microcapsules were 13.4 and 12.9 MPa, respectively and decreased
      significantly to 3.8 and 3.7 MPa, respectively, after heating. The temperature of
      the pulp wall increased 1.8-3.6 degrees C after heating, less than that required
      to induce pulp damage. Based on the results, we conclude that heating for 8 s
      during debonding of ceramic brackets bonded using EDA containing 40 wt% heat
      expandable microcapsules is the most effective and safest method for the enamel
      and pulp.

PMID- 21946485
TI  - Geometric design method for occlusal outlines of complex class I and class II
      inlay cavities.
AB  - The purpose of this study was to establish a geometric design method for the
      occlusal outlines of complex inlay cavities as a continuation study of a previous
      design method for simple class I inlay cavity. A method for extending the
      occlusal outline to the buccal or lingual groove and to three preparation types
      of the proximal portions of class II inlay cavities -namely, straight line
      preparation, sweeping curve preparation, and reverse curve preparation- was
      investigated. To ensure the smoothness of the occlusal outline, a Bezier curve
      was introduced in the design. A minimal number of control points for the curve
      was applied to define each preparation type. The design method was experimentally
      applied to mandibular and maxillary first molars. Smooth outlines of the complex
      inlay cavities in the molars with tool accessibility throughout the cavities were
      achievable by using the present method.

PMID- 21946486
TI  - Long-term regional bond strength of three MMA-based adhesive resins in simulated
      vertical root fracture.
AB  - The purpose of this study was to investigate bond durability of MMA-based
      adhesives to root dentin in a simulated complete vertical root fracture (CVRF).
      The fractured fragments of human premolar root were reattached using Super-Bond
      C&B (SB; Sun Medical), M-Bond or M-Bond II (MB or MB II; Tokuyama Dental). After
      storage for 1 day, 1 month, 6 months and 1 year, the reattached specimens were
      subjected to microtensile bond strength (uTBS) test at cervical and apical
      regions. Results showed that uTBS was significantly higher to cervical dentin
      than to apical dentin in MB and MB II, but not SB (p<0.05). Significant decrease
      in uTBS was found for MB and MB II after 1 year, whereas no significant
      difference was found for SB (p<0.05). Analysis of failure mode by SEM indicated
      differences over time. In conclusion, significant differences were found in the
      regional bond durability among MMA-based adhesives used to restore CVRF, that may
      lead to different clinical performances.

PMID- 21946487
TI  - Development of an orthodontic elastic material using EMA-based resin combined
      with 1-butanol.
AB  - For the development of new orthodontic elastic material, 1-butanol was added to
      PEMA-TA/HX resin. In the present study, basic experiments to reveal the
      mechanical properties of the materials were conducted. FT-IR spectroscopy showed
      that addition of 1-butanol did not cause any chemical changes to the PEMA-TA/HX
      resin. After addition of 1-butanol to PEMA-TA/HX resin, the modulus of
      elasticity, instantaneous modulus elasticity, retarded elasticity and viscosity
      were lowered in a concentration-dependent manner, whereas the elastic strain was
      increased in a concentration-dependent manner. Moreover, on the application of
      heat a shape-memory effect was observed. These results suggest that the modulus
      of elasticity of this material can be adjusted. Additionally, this material has
      the ability to restore force as a function of its shape-memory effect in cases of
      plastic deformation at the insertion of appliances. This new orthodontic elastic
      material has the potential to be clinically effective in orthodontic treatment.

PMID- 21946488
TI  - Hydroxyapatite particle characteristics influence the enhancement of the
      mechanical and chemical properties of conventional restorative glass ionomer
      cement.
AB  - The aims of this study were to improve the mechanical and chemical properties of
      conventional restorative glass ionomer cement (GIC) by adding hydroxyapatite
      (HAp) preparations with different characteristics, and to investigate the
      underlying reaction mechanisms. Fuji IX GP(r) was used as the control GIC. The
      experimental GICs consisted of four HAp-particles with different characteristics
      added at 8 mass% to Fuji IX-powder. All cements were prepared by mixing with Fuji
      IX-liquid (P/L=3.6). Four HAp-particles were analyzed, and then the mechanical
      strengths and the fluoride-ion- release-recharge-behaviors of five GIC groups
      were evaluated. The results of this study demonstrate that the addition of HAp
      particles with highly reactive properties such as high specific surface area can
      enhance the flexural strength and fluoride ion release properties of conventional
      restorative GIC. Our results further indicate that HAp functions as an adsorbent
      and an ion exchangeable agent, resulting in improved mechanical and chemical
      properties of GIC.

PMID- 21946489
TI  - Photoelastic stress analysis of different prefabricated post-and-core materials.
AB  - The purpose of this study was to investigate stress developed by a combination of
      a stainless steel post or a fiber-reinforced resin post with a silver amalgam
      core or a composite resin core. Two-dimensional photoelastic models were used to
      simulate root dentin.  Posts (ParaPost XT and ParaPost-FiberWhite) were cemented
      with a luting agent (RelyX Unicem).  Silver amalgam cores and composite resin
      cores were fabricated on the posts. Complete crowns were fabricated and cemented
      on the cores. Each model was analyzed with 2 force magnitudes and in 2
      directions.  Fringe orders were recorded and compared using ANOVA (p=0.05) and
      the Scheffe's test. With vertical force, no stress differences occurred among the
      4 groups (p=0.159). With a 30-degree force, there was stress differences among
      the 4 groups (p<0.001). The combination of a fiber-reinforced post and composite
      resin core could potentially reduce stresses within the radicular dentin when
      angled loads are applied.

PMID- 21946490
TI  - Antimicrobial and antifungal effects of tissue conditioners containing a
      photocatalyst.
AB  - This study examined the antimicrobial/antifungal ability of a tissue conditioner
      containing a photocatalyst for Escherichia coli, Streptococcus mutans,
      Staphylococcus aureus and Candida albicans. The photocatalyst was mixed with
      tissue conditioners powders at concentrations of 0, 10, 15, and 20 wt%. Tissue
      conditioners powders containing a photocatalyst were mixed with liquid to make
      test specimens. Test specimens inoculated by each microorganism were irradiated
      by ultraviolet light for 0-, 2- and 4 hours. The antimicrobial/antifungal effects
      were evaluated by the CFU technique. The CFU values of each microorganism for
      tissue conditioners containing a photocatalyst showed significant decrease
      following UV-irradiation. The improvement in antimicrobial/antifungal effects was
      concomitant with the increase of the mixing ratio and the irradiation time.
      Therefore, the results indicated that tissue conditioners containing a
      photocatalyst might have photocatalytic ability.

PMID- 21946491
TI  - Characterization of different water/powder ratios of dental gypsum using fiber
      Bragg grating sensors.
AB  - The impact of five different water/powder (w/p) ratios in the characterization of
      high strength dental stone was evaluated, since the recommendations of the
      gypsum' manufacturers are not always correctly followed by the dental prosthesis
      technicians. Fiber Bragg grating (FBG) sensors were used to measure the setting
      expansion and temperature variation which occurred during the setting reaction
      for each w/p ratio, as well as the thermal expansion coefficient. Thick mixtures
      with low w/p ratios had more crystals impinging upon each other during crystal
      growth, resulting in more expansion and more heat released. This thermal behavior
      was only achieved to w/p ratios within the manufacturer-recommended mixing ratio
      range. The results also revealed the existence of boundary condition; this
      corresponding to the limit of the mixing ratio recommended by the gypsum'
      manufacturer. Data provided in this study are particularly important for dental
      technicians with a view to attaining the best results in accuracy of fit for
      their prosthetic works.

PMID- 21946492
TI  - Osteoanagenesis after transplantation of bone marrow-derived mesenchymal stem
      cells using polyvinylidene chloride film as a scaffold.
AB  - The aim of this study was to develop a new cell transplantation technique for
      osteoanagenesis at bone defect sites. Polyvinylidene chloride (PVDC) film was
      evaluated because of its good biocompatibility and flexibility. We used this film
      as both a cell scaffold and a barrier membrane. Initially, the cell compatibility
      of the PVDC film for fibroblast-like cells and osteoblast-like cells was
      confirmed. Subsequently, bone marrow cells were obtained from rats and cultured
      on PVDC films in two kinds of medium. The PVDC films with bone marrow-derived
      mesenchymal stem cells (MSCs) were then applied to critical-sized bone defects in
      the calvarial bone of rats. After the transplantation, the surgical sites were
      dissected out and evaluated by soft X-ray radiography, micro-CT analysis and
      histological examinations. The bone marrow-derived MSC-transplanted rats showed
      greater bone regeneration than the control rats. Therefore, PVDC film is
      considered to be useful as a scaffold for bone regeneration.

PMID- 21946493
TI  - Effect of EDTA treatment on the hybrid layer durability in total-etch dentin
      adhesives.
AB  - The effect of the ethylenediaminetetraacetic acid (EDTA) treatment on the hybrid
      layer durability of total-etch dentin adhesives was investigated. A flat dentin
      surface was exposed and treated with 37% phosphoric acid or 0.1 M EDTA. Dentin
      adhesive was applied and a 4 mm thick composite resin was built-up. Twenty
      0.9*0.9 mm(2) resin-dentin beams were fabricated in each experimental group.
      Artificial aging with 10% NaClO was performed in half of the experimental groups
      for 1 hour. A micro-tensile bond strength (uTBS) test was performed and the
      bonded interface was analyzed with transmission electron microscopy (TEM). The
      37% phosphoric acid-treated group showed a lower uTBS after artificial aging,
      whereas the 0.1 M EDTA-treated group did not. TEM analysis revealed collagen
      fibrils dissolved in the 37% phosphoric acid-treated group but not in the 0.1M
      EDTA-treated group. Undissolved minerals were observed in the 0.1 M EDTA-treated
      group. In conclusion, a dentin treatment with 0.1M EDTA is effective in improving
      the hybrid layer durability.

PMID- 21946494
TI  - Effect of light units on tooth bleaching with visible-light activating titanium
      dioxide photocatalyst.
AB  - This study evaluated the influence of different light sources on the efficiency
      of an office bleaching agent containing visible-light activating titanium dioxide
      photocatalyst (VL-TiO(2)) using an artificial discoloration tooth model.
      Extracted bovine teeth were stained by black tea. The CIE L*a*b* values were
      measured before and after nine consecutive treatments by the VL-TiO(2)-containing
      bleaching agent (TiON in Office, GC, Tokyo, Japan). A halogen light unit (CB;
      CoBee, GC) or an LED unit (G-light, GC) with two modes (blue and violet: GL-BV,
      blue: GL-B) were used to activate the bleaching agent in three groups (n=8).
      Brightness (DeltaL) and color difference (DeltaE) increased as bleaching repeated
      in all groups. Two-way ANOVA showed that both number of treatments and light
      sources significantly affected DeltaE (p<0.05). GL-BV showed better bleaching
      effect than GL-B. In measurement of irradiation spectra, CB showed a wide
      spectrum (380-530 nm), GL-B had a sharp peak at 470 nm and GL-BV showed an
      additional peak at 405 nm. It was concluded that the light source influenced the
      efficiency of the tooth bleaching with VL-TiO(2).

PMID- 21946495
TI  - Cellular compatibility of a gamma-irradiated modified siloxane-poly(lactic acid)
      calcium carbonate hybrid membrane for guided bone regeneration.
AB  - A bi-layered silicon-releasable membrane consisting of a siloxane-poly(lactic
      acid) (PLA)-vaterite hybrid material (Si-PVH) microfiber mesh and a PLA
      microfiber mesh has been developed by an electrospinning method for guided bone
      regeneration (GBR) application. The bi-layered membrane was modified to a three
      laminar structure by sandwiching an additional PLA microfiber mesh between the Si
      PVH and PLA microfiber meshes (Si-PVH/PLA membrane). In this study, the influence
      of gamma irradiation, used for sterilization, on biological properties of the Si
      PVH/PLA membrane was evaluated with osteoblasts and fibroblasts. After gamma
      irradiation, while the average molecular weight of the Si-PVH/PLA membrane
      decreased, the Si-PVH/PLA membrane promoted cell proliferation and
      differentiation (alkaline phosphatase activity and calcification) of osteoblasts,
      compared with the poly(lactide-co-glycolide) membrane. These results suggest that
      the gamma-irradiated Si-PVH/PLA membrane is biocompatible with both fibroblasts
      and osteoblasts, and may have an application for GBR.

PMID- 21946496
TI  - Wear model simulating clinical abrasion on composite filling materials.
AB  - The aim of this study was to establish a wear model for testing composite filling
      materials with abrasion properties closer to a clinical situation. In addition,
      the model was used to evaluate the effect of filler volume and particle size on
      surface roughness and wear resistance. Each incisor tooth was prepared with nine
      identical standardized cavities with respect to depth, diameter, and angle.
      Generic composite of 3 different filler volumes and 3 different particle sizes
      held together with the same resin were randomly filled in respective cavities. A
      multidirectional wet-grinder with molar cusps as antagonist wore the surface of
      the incisors containing the composite fillings in a bath of human saliva at a
      constant temperature of 37 degrees C. The present study suggests that the most
      wear resistant filling materials should consist of medium filling content (75%)
      and that particles size is not as critical as earlier reported.

PMID- 21946497
TI  - Hydrothermal calcium modification of 316L stainless steel and its apatite forming
      ability in simulated body fluid.
AB  - To understand the feasibility of calcium (Ca) modification of type 316L stainless
      steel (316L SS) surface using hydrothermal treatment, 316L SS plates were treated
      hydrothermally in calcium chloride (CaCl(2)) solution. X-ray photoelectron
      spectroscopic analysis revealed that the surface of 316L SS plate was modified
      with Ca after hydrothermal treatment at 200 degrees C. And the immobilized Ca
      increased with CaCl(2) concentration. However no Ca-modification was occurred for
      316L SS plates treated at 100 degrees C. When Ca-modified 316L SS plate was
      immersed in simulated body fluid (SBF) with ion concentrations nearly equal to
      those of human blood plasma, low crystalline apatite was precipitated on its
      surface whereas no precipitate was observed on non Ca-modified 316L SS. The
      results obtained in the present study indicated that hydrothermal treatment at
      200 degrees C in CaCl(2) solution is useful for Ca-modification of 316L SS, and
      Ca-modification plays important role for apatite precipitation in SBF.

PMID- 21946498
TI  - Synthesis of novel oxide layers on titanium by combination of sputter deposition
      and micro-arc oxidation techniques.
AB  - A novel coating technique of thin ceramic layer resembling teeth color on
      titanium (Ti) surface was developed by combination of sputter deposition of metal
      zirconium (Zr) and subsequent micro-arc oxidation (MAO) treatment. The oxide
      layer grown by MAO treatment had a porous structure with a thickness of
      approximately 6 micrometers and was mainly composed of zirconium dioxide (ZrO(2))
      with both tetragonal and monoclinic crystal structures. The surface of the
      specimen was hardened by this technique, and the hardness of the specimen was
      significantly larger than that of untreated Ti and MAO-treated Ti without Zr
      layer. The bonding strength test revealed that fracture occurred inside the oxide
      layer, indicating that adhesion between the oxide layer and the Ti substrate was
      sufficiently strong. From these results, this technique has an advantage for the
      development of novel dental materials with excellent mechanical and aesthetic
      properties.

PMID- 21946499
TI  - K-Ras and mitochondria: dangerous liaisons.

PMID- 21946501
TI  - Tranexamic acid could really be recommended in case of subarachnoid hemorrhage?

PMID- 21946502
TI  - The awesome power of a $30 seat belt: an early recollection of M. Gazi Yasargil.

PMID- 21946500
TI  - p38alpha controls erythroblast enucleation and Rb signaling in stress
      erythropoiesis.
AB  - Enucleation of erythroblasts during terminal differentiation is unique to
      mammals. Although erythroid enucleation has been extensively studied, only a few
      genes, including retinoblastoma protein (Rb), have been identified to regulate
      nuclear extrusion. It remains largely undefined by which signaling molecules, the
      extrinsic stimuli, such as erythropoietin (Epo), are transduced to induce
      enucleation. Here, we show that p38alpha, a mitogen-activated protein kinase
      (MAPK), is required for erythroid enucleation. In an ex vivo differentiation
      system that contains high Epo levels and mimics stress erythropoiesis, p38alpha
      is activated during erythroid differentiation. Loss of p38alpha completely blocks
      enucleation of primary erythroblasts. Moreover, p38alpha regulates erythroblast
      enucleation in a cell-autonomous manner in vivo during fetal and anemic stress
      erythropoiesis. Markedly, loss of p38alpha leads to downregulation of p21, and
      decreased activation of the p21 target Rb, both of which are important regulators
      of erythroblast enucleation. This study demonstrates that p38alpha is a key
      signaling molecule for erythroblast enucleation during stress erythropoiesis.

PMID- 21946505
TI  - Device innovation in neurosurgery:  controversy, learning, and future directions.
AB  - Innovation in medicine has led to advances directly benefitting patients. Yet
      recent legislation has created intense scrutiny of the relationship between
      surgeons and industry. Critics argue that surgeon-held patents and royalties
      incentivize surgeon loyalty, influencing decision making as to which devices are
      used intraoperatively. We explored the potential for inventor-related conflicts
      of interest. We searched patent records from the United States Patent and
      Trademark Office for every diplomate recognized by the American Board of
      Neurological Surgeons (4868 neurosurgeons). We also searched physician payment
      registries of the 5 largest device makers; of these, Medtronic, DePuy, and Zimmer
      were the only companies with available registries. A total of 147 neurosurgeons
      (3.0%) hold a total of 582 patents; the number of patents held per neurosurgeon
      ranges from 1 to 53. The fields in which patents are held include tumor (125),
      spine (98), vascular (54), trauma (27), stereotaxy/image guidance (88), pain
      (19), peripheral nerve (2), electrical stimulation (63), and pediatrics (9);
      surgical instruments (59), drug delivery (17), and other (21) account for the
      remainder. The total amount of royalties received by neurosurgeons in 2010 is
      expected to be $13,223,000 (minimum: $7K, maximum: $8.261M). Despite public and
      legislative perceptions of widespread conflicts of interest, there are relatively
      few neurosurgeons who hold patents and receive significant royalties.

PMID- 21946503
TI  - In-training factors predictive of choosing and sustaining a productive academic
      career path in neurological surgery.
AB  - BACKGROUND: Factors during neurosurgical residency that are predictive of an
      academic career path and promotion have not been defined. OBJECTIVE: To determine
      factors associated with selecting and sustaining an academic career in
      neurosurgery by analyzing in-training factors for all graduates of American
      College of Graduate Medical Education (ACGME)-accredited programs between 1985
      and 1990. METHODS: Neurological surgery residency graduates (between 1985 and
      1990) from ACGME-approved training programs were analyzed to determine factors
      associated with choosing an academic career path and having academic success.
      RESULTS: Information was available for 717 of the 720 (99%) neurological surgery
      resident training graduates (678 male, 39 female). One hundred thirty-eight
      graduates (19.3%) held full-time academic positions. One hundred seven (14.9%)
      were professors and 35 (4.9%) were department chairs/chiefs. An academic career
      path/success was associated with more total (5.1 vs 1.9; P < .001) and first
      author publications (3.0 vs 1.0; P < .001) during residency. Promotion to
      professor or chair/chief was associated with more publications during residency
      (P < .001). Total publications and first-author publications were independent
      predictors of holding a current academic position and becoming professor or
      chair/chief. Although male trainees published more than female trainees (2.6 vs
      0.9 publications; P < .004) during training, no significant sex difference was
      observed regarding current academic position. Program size (>= 2 graduates a
      year; P = .02) was predictive of an academic career but not predictive of
      becoming professor or chair/chief (P > .05). CONCLUSION: Defined in-training
      factors including number of total publications, number of first-author
      publications, and program size are predictive of residents choosing and
      succeeding in an academic career path.

PMID- 21946506
TI  - Decompressive craniectomy in children:  single-center series and systematic
      review.
AB  - BACKGROUND: Decompressive craniectomy (DC) is performed as a life-saving
      procedure in patients with intractably increased intracranial pressure after
      traumatic brain injury, bleeding, cerebral infarction, or brain swelling of other
      causes. However, the application of DC is as controversial in the pediatric
      population as it is in adults. OBJECTIVE: To find factors influencing the outcome
      in pediatric patients who underwent DC because of sustained high intracranial
      pressure. METHODS: Between April 2000 and December 2009, 34 pediatric patients
      (age 0-18 years) underwent DC. Patients were stratified according to the
      indication for DC. Outcome was assessed according to the modified Rankin Scale
      score at 6 months. MEDLINE was searched for published studies or reports of DC in
      pediatric patients to gain a larger population. Two reviewers independently
      extracted data. RESULTS: Literature data, including the current series, revealed
      a total of 172 pediatric patients. Overall, a favorable outcome was achieved in
      106 of 172 patients (62%). A favorable outcome was achieved in 25 of 36 patients
      without traumatic brain injury vs 81 of 136 patients with traumatic brain injury
      (69% vs 60%). Patients without signs of cerebral herniation had a better outcome
      than patients with unilateral or bilateral dilated pupils (73% vs 60% vs 45%,
      respectively). CONCLUSION: The current data indicate that DC in children with
      traumatic or nontraumatic brain swelling might be warranted, regardless of the
      underlying cause. Despite mydriasis, a favorable outcome might be achieved in a
      significant number of pediatric patients. Nevertheless, careful individual
      decision making is needed for each patient, especially when signs of cerebral
      herniation have persisted for a long time.

PMID- 21946507
TI  - Is there a causal relationship between open spinal dysraphism and Chiari II
      deformity? A study using in utero magnetic resonance imaging of the fetus.
AB  - BACKGROUND: Chiari II deformity is associated with open spinal dysraphism. A
      causal relationship has been proposed by McLone and Knepper. This article
      evaluates that hypothesis. OBJECTIVE: To establish the frequency of Chiari II
      deformity in fetuses with open spinal dysraphism, assess whether meningocele sac
      neck area and volume influence the severity of posterior fossa changes, and
      assess whether the severity of associated findings (ventriculomegaly, amount of
      extracerebral CSF) are associated with Chiari II deformity. METHODS: Sixty-five
      fetuses with open spinal dysraphism were compared with gestationally aged matched
      "normal" fetuses on ultrafast MR images. Cerebellar vermis and bony posterior
      fossa surface area were measured on midline sagittal images. Hindbrain herniation
      was noted if present. In the open spinal dysraphic group, sac neck area and
      volume were measured. Ventriculomegaly was assessed by linear measurement of the
      trigone of the lateral ventricle and extracerebral CSF depth was measured
      maximally over the lateral surface of the cerebral hemispheres. RESULTS: Fifteen
      of 65 fetuses with open spinal dysraphism did not have Chiari II deformity. Neck
      area and volume of the sac did not correlate with the presence of Chiari II
      deformity or reduction in bony posterior fossa size. CONCLUSION: A relatively
      high proportion of fetuses with open spinal dysraphism do not have Chiari II
      deformity in utero. There is a lack of correlation between indicators of spinal
      dysraphism severity and the extent of the posterior fossa abnormality. This
      raises some interesting questions about the causality of the Chiari II deformity.

PMID- 21946509
TI  - Clinical assessment of percutaneous lumbar pedicle screw placement using theO-arm
      multidimensional surgical imaging system.
AB  - BACKGROUND: Increasing popularity of minimally invasive surgery for lumbar fusion
      has led to dependence upon intraoperative fluoroscopy for pedicle screw
      placement, because limited muscle dissection does not expose the bony anatomy
      necessary for traditional, freehand techniques nor for registration steps in
      image-guidance techniques. This has raised concerns about cumulative radiation
      exposure for both surgeon and operating room staff. The recent introduction of
      the O-arm Multidimensional Surgical Imaging System allows for percutaneous
      placement of pedicle screws, but there is limited clinical experience with the
      technique and data examining its accuracy. OBJECTIVE: We present the first large
      clinical series of percutaneous screw placement using navigation of O-arm imaging
      and compare the results with the fluoroscopy-guided method. METHODS: A
      retrospective review of a 24-month period identified patients undergoing
      minimally invasive lumbar interbody fusion. The O-arm was introduced in the
      middle of this period and was used for all subsequent patients. Accuracy of screw
      placement was assessed by examination of axial computed tomography or O-arm
      scans. RESULTS: The fluoroscopy group included 141 screws in 42 patients, and the
      O-arm group included 205 screws in 52 patients. The perforation rate was 12.8% in
      the fluoroscopy group and 3% in the O-arm group (P < .001). Single-level O-arm
      procedures took a mean 200 (153-241) minutes, whereas fluoroscopy took 221 (178
      302) minutes (P < .03). CONCLUSION: Percutaneous pedicle screw placement with the
      O-arm Multidimensional Intraoperative Imaging System is a safe and effective
      technique and provided improved overall accuracy and reduced operative time
      compared with conventional fluoroscopic techniques.

PMID- 21946508
TI  - Intraoperative visualization of fiber tracking based reconstruction of language
      pathways in glioma surgery.
AB  - BACKGROUND: For neuroepithelial tumors, the surgical goal is maximum resection
      with preservation of neurological function. This is contributed to by
      intraoperative magnetic resonance imaging (iMRI) combined with multimodal
      navigation. OBJECTIVE: We evaluated the contribution of diffusion tensor imaging
      (DTI)-based fiber tracking of language pathways with 2 different algorithms
      (tensor deflection, connectivity analysis [CA]) integrated in the navigation on
      the surgical outcome. METHODS: We evaluated 32 patients with neuroepithelial
      tumors who underwent surgery with DTI-based fiber tracking of language pathways
      integrated in neuronavigation. The tensor deflection algorithm was routinely used
      and its results intraoperatively displayed in all cases. The CA algorithm was
      furthermore evaluated in 23 cases. Volumetric assessment was performed in pre-
      and intraoperative MR images. To evaluate the benefit of fiber tractography,
      language deficits were evaluated pre- and postoperatively and compared with the
      volumetric analysis. RESULTS: Final gross-total resection was performed in 40.6%
      of patients. Absolute tumor volume was reduced from 55.33 +/- 63.77 cm(3) to
      20.61 +/- 21.67 cm(3) in first iMRI resection control, to finally 11.56 +/- 21.92
      cm(3) (P < .01). Fiber tracking of the 2 algorithms showed a deviation of the
      displayed 3D objects by <5 mm. In long-term follow-up only 1 patient (3.1%) had a
      persistent language deficit. CONCLUSION: Intraoperative visualization of language
      related cortical areas and the connecting pathways with DTI-based fiber tracking
      can be successfully performed and integrated in the navigation system. In a
      setting of intraoperative high-field MRI this contributes to maximum tumor
      resection with low postoperative morbidity.

PMID- 21946510
TI  - Epilepsy surgery of the cingulate gyrus and the frontomesial cortex.
AB  - BACKGROUND: Epilepsy surgery involving the cingulate gyrus has been mostly
      presented as case reports, and larger series with long-term follow-up are not
      published yet. OBJECTIVE: To report our experience with focal epilepsy arising
      from the cingulate gyrus and surrounding structures and its surgical treatment.
      METHODS: Twenty-two patients (mean age, 36; range, 12-63) with a mean seizure
      history of 23 years (range, 2-52) were retrospectively analyzed. We report
      presurgical diagnostics, surgical strategy, and postoperative follow-up
      concerning functional morbidity and seizures (mean follow-up, 86 months; range,
      25-174). RESULTS: Nineteen patients showed potential epileptogenic lesions on
      preoperative magnetic resonance imaging (MRI). All patients had noninvasive
      presurgical workup; 15 (68%) underwent invasive Video-electroencephalogram (EEG)
      Monitoring. In 12 patients we performed extended lesionectomy according to MRI;
      an extension with regard to EEG results was done in 6 patients. In 4 patients,
      the resection was incomplete because of the involvement of eloquent areas
      according to functional mapping results. Eight pure cingulate resections (36%, 3
      in the posterior cingulate gyrus) and 14 extended supracingular frontal
      resections were performed. Nine patients experienced temporary postoperative
      supplementary motor area syndrome after resection in the superior frontal gyrus.
      Two patients retained a persistent mild hand or leg paresis, respectively.
      Postoperatively, 62% of patients were seizure-free (International League Against
      Epilepsy [ILAE] 1), and 76% had a satisfactory seizure outcome (ILAE 1-3).
      CONCLUSION: Epilepsy surgery for lesions involving the cingulate gyrus represents
      a small fraction of all epilepsy surgery cases, with good seizure outcome and low
      rates of postoperative permanent deficits. In case of extended supracingular
      resection, supplementary motor area syndrome should be considered.

PMID- 21946511
TI  - Safe resection of arteriovenous malformations in eloquent motor areas aided by
      functional imaging and intraoperative monitoring.
AB  - BACKGROUND: Arteriovenous malformations (AVMs) proximal to motor cortical areas
      or motor projection systems are challenging to manage because of the risk of
      severe sensory and motor impairment. Surgical indication in these cases therefore
      remains controversial. OBJECTIVE: To propose a standardized approach for
      centrally situated AVMs based on functional imaging and intraoperative
      electrophysiological evaluation. METHODS: We conducted a retrospective analysis
      of 15 patients who underwent surgical treatment for AVMs in motor cortical areas
      or proximal to motor projections. Preoperative assessment included functional
      magnetic resonance and 3-dimensional tractography. Operations were performed
      under continuous electrophysiological monitoring aided by direct brain
      stimulation. We identified critical bloody supply to the motor areas by temporary
      occluding the feeding vessels under electrophysiological monitoring. Clinical
      outcome was evaluated with the modified Rankin Scale. RESULTS: Total resection
      was achieved in 12 cases, whereas electrophysiology limited total extirpation in
      3 cases. A significant reduction of motor evoked potentials by up to 15% of the
      initial values was associated with good recovery of motor function; in contrast,
      the disappearance of potentials correlated with long-term impairment. The mean
      follow-up time was 13 months, and clinical assessments revealed overall
      functional improvement (P < .05). After surgery, 11 patients were asymptomatic or
      presented with only minor neurological deficits. CONCLUSION: Surgical resection
      of AVMs in eloquent motor areas can be considered a safe option for selected
      cases when performed in conjunction with a detailed functional assessment.
      Possible selection criteria for surgical treatment are discussed in light of the
      presented clinical data.

PMID- 21946513
TI  - Repeated brain conventional MRI and SPECT evaluation in systemic lupus
      erythematosus patients with and without neuropsychiatric involvement: a follow up
      study.
AB  - OBJECTIVES: To assess the utility of a combined neuroimaging approach in the
      follow up of patients affected by systemic lupus erythematosus (SLE) with and
      without neuropsychiatric (NP) involvement. METHODS: Patients who underwent a
      first combined brain conventional magnetic resonance imaging (cMRI) and single
      photon emission computed tomography (SPECT) and later repeated the same
      examinations between 2001 and 2008 were retrieved from a large database. Clinical
      and neuroimaging data were analysed and their relationships evaluated at baseline
      and at follow up. RESULTS: Fifty SLE patients (38 with and 12 without NP
      involvement, mean age 36.8 yrs and mean disease duration at first instrumental
      evaluation 5.5 yrs) were enrolled. At baseline, the majority of them had a
      diffuse pattern of NP involvement. After a mean follow up period of 4 years all
      patients repeated neuroimaging and clinical evaluation. In 23 patients (22 with
      and 1 without NP manifestations at baseline) a new NP event occurred. Overall,
      neuroimaging remained unchanged or improved, but in some cases it worsened. No
      correlations were found between instrumental findings and clinical picture.
      CONCLUSIONS: In this study, the clinical features at baseline appeared to be a
      better predictor of future NP events than morphological and functional
      neuroimaging. Therefore the utility of repeating a combined instrumental
      evaluation (cMRI and SPECT) may be debatable especially for patients with diffuse
      NP involvement where the decision to perform serial combined neuroimaging
      examinations should be carefully assessed and based mainly on clinical judgement.

PMID- 21946514
TI  - Antinucleosome antibodies as a potential biomarker for the evaluation of renal
      pathological activity in patients with proliferative lupus nephritis.
AB  - The objective of this study is to evaluate the correlation between antinucleosome
      antibodies and renal pathological activity in patients with proliferative lupus
      nephritis (LN). We evaluated 36 patients with proliferative LN, 14 non-renal
      lupus patients and 10 healthy volunteers. Lupus activity was assessed using the
      British Isles Lupus Assessment Group 2004 (BILAG 2004) index, serum anti-double
      stranded DNA (anti-dsDNA) levels, serum complement levels and daily urinary
      protein levels. All 36 lupus nephritis patients received renal biopsy.
      Antinucleosome antibodies were detected by enzyme-linked immunosorbent assay
      (ELISA). Our results showed that levels of serum antinucleosome antibodies were
      significantly higher in LN patients (median 90.35 units/ml, interquartile range
      [IQR] 37.38-135.23) than in non-renal SLE patients (median 5.45 units/ml, IQR 2.6
      28.93, p <0.05) and in healthy volunteers (median 3.35 units/ml, IQR 2.95-5.23, p
      <0.001). Serum levels of antinucleosome antibodies were positively correlated
      with BILAG index (Spearman's r = 0.645, p <0.001) and serum anti-dsDNA antibody
      levels (r(s) = 0.644, p <0.01), while serum levels of antinucleosome antibodies
      were negatively correlated with serum levels of C3 (r(s) = -0.400, p <0.01) and
      C4 (r(s) = -0.300, p <0.05). Serum levels of antinucleosome antibodies were
      positively correlated with the histological activity index of LN (r(s) = 0.368, p
      <0.05). However, there was no significant correlation between serum levels of
      antinucleosome antibodies and the histological chronicity index. In conclusion,
      the serum level of antinucleosome antibodies is a potential biomarker for early
      recognition of renal involvement and evaluation of disease activity in SLE. Our
      preliminary results suggested that serum levels of antinucleosome antibodies
      might be a potential biomarker in evaluating pathological activity of LN.

PMID- 21946515
TI  - Rationale and methods for site selection for a trial using a novel intervention
      to treat stimulant abuse.
AB  - Although the selection of appropriate clinical sites has a significant impact on
      the successful conduct of clinical trials, no generally accepted model is
      available for site selection. Use of an appropriate site selection process is
      even more pertinent when conducting large scale, practical clinical trials in
      practice settings. This report provides a rationale for selecting sites by
      identifying both a set of basic site selection criteria important to most trials
      as well as criteria specific to the features of a particular study's design. In
      this two-tier system, although all these criteria must be met, some criteria are
      firm and viewed as essential for a site to conduct the trial. Other criteria,
      such as those that support study recruitment or participant retention, are
      flexible. These flexible criteria may be addressed through several alternative
      solutions that meet the original intent of the criterion. We illustrate how the
      study specific features and requirements of Stimulant Reduction Intervention
      using Dosed Exercise (STRIDE), a multisite clinical trial evaluating the efficacy
      of exercise or health education, added to treatment as usual for stimulant abuse
      are linked to firm and flexible site selection criteria. We also present an
      iterative, multi-step approach to site selection including building awareness
      about the study and screening and evaluating sites using these criteria. This
      simple model could maximize the chance that selected sites will implement a study
      successfully and achieve trial aims. It may be helpful to researchers who are
      developing criteria and methods for site selection for specific clinical trials.

PMID- 21946516
TI  - TAp73 is downregulated in oocytes from women of advanced reproductive age.
AB  - Studies on oocyte transcriptome are important to understand the biological
      pathways involved in oogenesis, totipotence and early embryonic development.
      Moreover, genes regulating physiological pathways in gametes could represent
      potential candidates for reproductive disorders. In addition to oocyte specific
      transcription factors, also the members of the p53 family could be etiologically
      involved due to their biological functions. In fact, their role in the control of
      cell cycle, apoptosis, and germ-line genome stability is well known. Female
      reproductive aging is one of the causes of fertility reduction and it is often
      associated with egg aneuploidy increase. In order to verify the potential
      involvement of p73 in reproductive aging, we determined its expression in single
      mature MII oocytes from two groups of women, younger than 35 or older than 38
      years, respectively. We found that TAp73 isoforms are down regulated in oocytes
      from women older than 38 years. We confirmed these data in pools of mouse
      oocytes. TAp73 down regulation in oocytes from women of advanced reproductive age
      could explain both the reduction of fertility and the increase of newborns with
      chromosomal abnormalities.

PMID- 21946517
TI  - "Micromanaging" metabolic syndrome.
AB  - Metabolic diseases are characterized by the failure of regulatory genes or
      enzymes to effectively orchestrate specific pathways involved in the control of
      many biological processes. In addition to the classical regulators of metabolic
      homeostasis, recent discoveries have shown the remarkable role of small non
      coding RNAs (microRNAs) in the post-transcriptional regulation of a number of
      genes, and their involvement in many pathological states, such as diabetes,
      atherosclerosis and cancer. Of note is microRNA-33 (miR-33), an intronic microRNA
      (miRNA) located within the sterol regulatory element-binding protein (SREBP)
      genes, one of the master regulators of cholesterol and fatty acid metabolism. We
      have recently shown that miR-33 regulates cholesterol efflux and high-density
      lipoprotein (HDL) formation, as well as fatty acid oxidation and insulin
      signaling. These results describe a model in which miR-33 works in concert with
      its host genes to ensure that the cell's metabolic state is balanced, thus
      highlighting the clinical potential of miRNAs as novel therapeutic targets for
      treating cardiometabolic diseases.

PMID- 21946518
TI  - Lamins, guardians of the soma and the genome.

PMID- 21946519
TI  - Novel role of Wip1 in p53-mediated cell homeostasis under non-stress conditions.

PMID- 21946520
TI  - Checking before changing: cell cycle checkpoints inhibit muscle differentiation.

PMID- 21946521
TI  - Taccalonolides: a microtubule stabilizer poses a new puzzle with old pieces.

PMID- 21946522
TI  - miR-27a regulation of SCF(Fbw7) in cell division control and cancer.

PMID- 21946523
TI  - Autophagic tumor stroma: a biofuel for cancer growth.

PMID- 21946524
TI  - DNA double-strand breaks make bedfellows of ATM and AKT.

PMID- 21946525
TI  - Preparing undercut model of posttraumatic epileptogenesis in rodents.
AB  - Partially isolated cortex ("undercut") is an animal model of posttraumatic
      epileptogenesis. The surgical procedure involves cutting through the sensorimotor
      cortex and the underneath white matter (undercut) so that a specific region of
      the cerebral cortex is largely isolated from the neighboring cortex and
      subcortical regions(1-3). After a latency of two or more weeks following the
      surgery, epileptiform discharges can be recorded in brain slices from rodents(1);
      and electrical or behavior seizures can be observed in vivo from other species
      such as cat and monkey(4-6). This well established animal model is efficient to
      generate and mimics several important characteristics of traumatic brain injury.
      However, it is technically challenging attempting to make precise cortical
      lesions in the small rodent brain with a free hand. Based on the procedure
      initially established in Dr. David Prince's lab at the Stanford University(1),
      here we present an improved technique to perform a surgery for the preparation of
      this model in mice and rats. We demonstrate how to make a simple surgical device
      and use it to gain a better control of cutting depth and angle to generate more
      precise and consistent results. The device is easy to make, and the procedure is
      quick to learn. The generation of this animal model provides an efficient system
      for study on the mechanisms of posttraumatic epileptogenesis.

PMID- 21946526
TI  - Distribution of culprit lesions in patients with ST-segment elevation acute
      myocardial infarction treated with primary percutaneous coronary intervention.
AB  - OBJECTIVES: Data regarding the distribution of vulnerable lesions in the coronary
      arteries are scarce. The aim was to evaluate the frequency and distribution of
      culprit lesions in patients with ST-segment elevation acute myocardial
      infarction. In addition, the location of culprit lesions was related to infarct
      size. METHODS: Consecutive patients (N=1533, mean age 61+/-12 years) were
      evaluated. All patients were treated with primary percutaneous coronary
      intervention and underwent two-dimensional echocardiography less than 48 h after
      admission. RESULTS: The majority of the culprit lesions were located in the left
      anterior descending coronary artery (LAD, 45%), followed by the right coronary
      artery (RCA, 38%), and left circumflex coronary artery (LCX, 14%). Subanalysis
      demonstrated that patients with a culprit lesion in the LAD and LCX had
      significantly higher-peak cardiac enzymes compared with patients with culprit
      lesions in the RCA. In addition, patients with proximal LAD and LCX lesions had
      significantly worse left ventricular function compared with patients with mid or
      distal lesions. CONCLUSION: Plaque rupture resulting in acute myocardial
      infarction is more likely to occur in the proximal parts of the LAD and RCA. In
      addition, the location of culprit lesions was related to infarct size. Therefore,
      knowledge of the distribution of vulnerable lesions is important for identifying
      patients at risk for acute coronary events.

PMID- 21946527
TI  - Outcomes of patients with left main coronary artery disease undergoing medical or
      surgical treatment:  a propensity-matched analysis.
AB  - OBJECTIVE: To evaluate the outcomes of patients with significant (>= 50%) left
      main coronary artery disease (LMCAD) undergoing medical treatment (MT) or
      coronary artery bypass grafting surgery (CABG). METHODS: A total of 181 patients
      with significant LMCAD were followed for 4 +/- 2 years. MT was done when patients
      refused CABG or because of either thin native vessels or high clinical risk.
      Events were defined as all-cause death, myocardial infarction, percutaneous
      coronary intervention, or subsequent CABG. Logistic regression analysis was used
      to identify independent predictors of death. A propensity score was created to
      compare outcomes of patients from the two treatment groups. RESULTS: CABG was
      performed in 78.5% of the patients. Overall, there were no significant
      differences in the incidences of death or other events between treatment groups.
      In patients with normal left ventricular (LV) function (ejection fraction, >=
      45%), there were no significant differences in event rates with MT or CABG
      (death, 7.7 vs. 12.1%; myocardial infarction, 0 vs. 1.9%; percutaneous coronary
      intervention, 3.8 vs. 5.6%). For patients with LV dysfunction, death was more
      frequent with MT than with CABG (53.8 vs. 22.9%, P<0.001), whereas the incidence
      of other events was not statistically different. Age and LV dysfunction, but not
      treatment type, were independent predictors of death. When comparing propensity
      matched patients from both treatment groups, there was also no difference in
      survival. CONCLUSION: Patients with 50% or more LMCAD and LV dysfunction had
      increased survival with CABG. However, outcomes of patients with 50% or more
      LMCAD and normal LV function were not significantly different with either MT or
      CABG.

PMID- 21946528
TI  - Relationship between coronary artery plaque composition by virtual histology
      intravascular ultrasound analysis and brachial-ankle pulse wave velocity in
      patients with coronary artery disease.
AB  - OBJECTIVE: Brachial-ankle pulse wave velocity (baPWV) is an indicator of
      atherosclerotic cardiovascular risks. To identify patients with coronary
      atherosclerosis before the onset of angina pectoris or myocardial infarction will
      be desirable. METHODS: We measured the ankle-brachial index and baPWV in 150
      consecutive patients with coronary artery disease (CAD). Virtual histology
      intravascular ultrasound (VH-IVUS) imaging was available in target lesions of 130
      patients with symptomatic CAD before percutaneous intervention. Patients were
      divided into two groups: baPWV of greater than or equal to 1600 cm/s (74
      patients) and baPWV of less than 1600 cm/s (56 patients). RESULTS: Patient age
      was 66+/-8.33 years in baPWV of greater than or equal to 1600 cm/s group versus
      56+/-10.27 years in baPWV of less than 1600 cm/s group (P<0.0001). Although
      plaque burden and remodeling index were similar, minimal lumen area was smaller
      in baPWV of greater than or equal to 1600 cm/s group (P=0.039); and lesion length
      was longer in the baPWV of greater than or equal to 1600 cm/s group (P=0.033). VH
      IVUS analysis of coronary artery plaque composition showed that percent mean and
      percent maximum dense calcium were higher in the baPWV of greater than or equal
      to 1600 cm/s group (P=0.0037), and percent maximal calcium correlated with baPWV
      (r=0.278, P=0.001). CONCLUSION: We concluded that there is a significant
      relationship between baPWV and the VH-IVUS assessment of CAD. A high baPWV
      indicates more severe CAD (smaller minimal lumen area and longer lesion length)
      and greater atherosclerosis disease complexity (more calcified coronary plaque).

PMID- 21946529
TI  - Prognostic significance of baseline ST-T-wave abnormalities in diagnostic stress
      echocardiography.
AB  - OBJECTIVE: The aim of this study was to determine whether resting ST-T wave
      abnormalities (ST-Ta) provide incremental prognostic information in patients with
      no history of coronary artery disease undergoing dobutamine stress
      echocardiography (DSE). METHODS: We evaluated 1308 consecutive patients without
      previous myocardial infarction (MI) or revascularization who underwent DSE.
      Ischemia was defined as new or worsening wall motion abnormalities. End points
      during follow-up were all-cause death and cardiac death/nonfatal MI. RESULTS: ST
      Ta were detected in 162 (12%) patients. The incidence of ischemia was higher in
      patients with baseline ST-Ta than patients without [74 (46%) vs. 327 (28%),
      P=0.00001]. During a follow-up of 4.6 +/- 3 years, cardiac death/nonfatal MI
      occurred in 42 (26%) patients with resting ST-Ta and in 157 (14%) patients
      without resting ST-Ta (P<0.001). Patients with ST-Ta had a higher annual cardiac
      death/nonfatal MI rate compared with patients without, both in the presence of
      normal DSE (3.2 vs. 1.4%, P=0.01) as well as abnormal DSE (5.3 vs. 3%, P<0.001).
      In a Cox proportional modeling, resting ST-Ta added incremental value over
      clinical and stress echocardiographic data for the prediction of death (global
      chi 125, 140, 150, respectively; P<0.05) and cardiac death/nonfatal MI (global
      chi 79, 100, 111, respectively; P<0.05). CONCLUSION: Baseline ST-Ta are
      associated with an increased risk of cardiac death/nonfatal MI and all-cause
      mortality, incremental to clinical data and DSE results. The associated risk is
      persistent among patients with normal DSE.

PMID- 21946530
TI  - Long-term effects of the rhapontic rhubarb extract ERr 731(r) on estrogen
      regulated targets in the uterus and on the bone in ovariectomized rats.
AB  - The efficacy of ERr 731((r)), a commercially available extract isolated from
      Rheum rhaponticum, in terms of menopausal complaints like hot flushes,
      depression, anxiety and vaginal dryness has been proven in a two-year clinical
      study. Further a recent preclinical study excluded unwanted side effects on the
      endometrium by showing a lack of stimulation of proliferation marker genes by ERr
      731((r)) or its constituents in the 3-day uterotrophic assay. The present study
      aimed at further substantiating the safety of ERr 731((r)) in terms of
      endometrial hyperplasia and at the same time test for potential estrogenic
      effects in the bone. Therefore, ovariectomized (ovx) rats were treated in a
      dietary long-term administration for 90 days. Hence, the modulation of
      proliferation in the uterus was investigated by examining the effects on the mRNA
      expression of proliferation marker genes (Mki67, Pcna), on the estrogen
      responsive gene C3 and on the estrogen receptors ERalpha and ERbeta. We
      additionally performed densitometry analysis of the proximal tibia metaphysis
      using peripheral computed tomography (pQCT) and quantified bone homeostasis
      markers in the serum to examine potential effects on the bone. In this study
      design, neither an uterotrophic response nor a modulation of proliferation marker
      genes on mRNA level has been observed as response to the long-term application of
      the rhapontic extract. Furthermore, no impact of the two administered ERr
      731((r)) doses on the E2 deprivation-induced bone loss has been evident at the
      end of the study. In conclusion, the observations from previous trials regarding
      the endometrial safety of ERr 731((r)) have been supported by our experimental
      findings that exclude a stimulatory activity on proliferation in the uterus in a
      long-term administration in the young adult rat but no effect on the bone mineral
      density could be observed.

PMID- 21946531
TI  - Steroid-transforming enzymes in fungi.
AB  - Fungal species are a very important source of many different enzymes, and the
      ability of fungi to transform steroids has been used for several decades in the
      production of compounds with a sterane skeleton. Here, we review the
      characterised and/or purified enzymes for steroid transformations, dividing them
      into two groups: (i) enzymes of the ergosterol biosynthetic pathway, including
      data for, e.g. ERG11 (14alpha-demethylase), ERG6 (C-24 methyltransferase), ERG5
      (C-22 desaturase) and ERG4 (C-24 reductase); and (ii) the other steroid
      transforming enzymes, including different hydroxylases (7alpha-, 11alpha-, 11beta
      , 14alpha-hydroxylase), oxidoreductases (5alpha-reductase, 3beta-hydroxysteroid
      dehydrogenase/isomerase, 17beta-hydroxysteroid dehydrogenase, C-1/C-2
      dehydrogenase) and C-17-C-20 lyase. The substrate specificities of these enzymes,
      their cellular localisation, their association with protein super-families, and
      their potential applications are discussed. Article from a special issue on
      steroids and microorganisms.

PMID- 21946533
TI  - Fasting serum apolipoprotein B-48 can be a marker of postprandial hyperlipidemia.
AB  - AIM: Postprandial hyperlipidemia (PH) is thought to be caused by the impaired
      postprandial metabolism of triglycerides (TG)-rich lipoproteins in both
      endogenous and exogenous pathways; however, there is no consensus. It is
      difficult to estimate the presence of PH without performing a time-consuming oral
      fat loading (OFL) test, so postprandial lipoprotein metabolism was analyzed by
      measuring the postprandial levels of apolipoprotein (apo) B-48 and apo B-100, and
      the correlation between postprandial TG increase and fasting apoB-48 levels was
      assessed to establish a good marker of PH without performing an OFL test.
      METHODS: Ten male normolipidemic subjects were loaded with a high-fat (HF, 1045
      kcal) or standard (ST, 566 kcal) meal, and the lipids, apolipoproteins and
      lipoprotein profiles were analyzed after each meal. RESULTS: TG, apo B-48,
      remnant-like particles (RLP)-cholesterol and RLP-TG levels were increased and
      their levels were significantly higher after intake of the HF meal than the ST
      meal; however, there was no postprandial increase in apo B-100 and LDL-C levels.
      Postprandial increases in TG levels of CM, VLDL, LDL and HDL were significantly
      higher after intake of the HF meal than the ST meal. Fasting apo B-48 levels were
      strongly correlated with the incremental area under the curve of TG after intake
      of the HF meal, but not the ST meal. CONCLUSION: Postprandial TG increase was
      mainly due to increased CM and CM-R, but not VLDL. Measurement of fasting serum
      apo B-48 may be a simple and useful method for assessment of the existence of PH.

PMID- 21946534
TI  - Physical activity in the Japan population: association with blood lipid levels
      and effects in reducing cardiovascular and all-cause mortality.
AB  - According to many prospective cohort studies and meta-analyses of those studies,
      physical inactivity and/or low levels of physical fitness are associated with an
      elevated risk for the development of metabolic syndrome, type 2 diabetes,
      hypertension, coronary artery disease (CAD), and stroke, and with an increased
      risk of cardiovascular disease (CVD) mortality and all-cause mortality. Most of
      these analyses, however, were conducted on non-Japanese populations in the West.
      This report summarizes prospective observational and clinical studies in Japan.
      The annual national nutrition survey has shown a gradual decline in the number of
      walking steps in both genders and in all age groups over the last 10 years. While
      exercise habits have been gradually increasing in the elderly, only one-fifth of
      young and middle-aged people undertake leisure-time physical activity.
      Prospective cohort studies have shown that increased physical fitness and greater
      physical activity in either daily life or leisure time are of benefit in
      preventing all-cause mortality and CVD mortality. The daily number of walking
      steps is positively associated with HDL cholesterol levels and negatively
      associated with triglyceride levels. According to a random-effects model meta
      analysis of 4 randomized controlled trials comparing supervised aerobic exercise
      training with non-exercise control in subjects without CAD, exercise resulted in
      a significant increase in HDL-cholesterol (10.01 mg/dL, 95% CI 5.38 to 14.65, p<
      0.0001). While this confirms the importance of physical activity in preventing
      CVD mortality and all-cause mortality, the levels of physical activity are on a
      declining trend in Japan, particularly among the young.

PMID- 21946535
TI  - Deficiency of CuZn superoxide dismutase promotes inflammation and alters medial
      structure following vascular injury.
AB  - AIM: The anti-oxidant enzyme copper/zinc superoxide dismutase (CuZnSOD)
      metabolizes superoxide anion (O(2)(-)) in vascular cells. However, the role of
      CuZnSOD in vascular injury remains poorly understood. METHODS: Using CuZnSOD
      deficient (CuZnSOD(-/-)) mice and wild-type (WT) mice, we investigated
      morphometric changes and the role of O(2)(-) in vascular remodeling after femoral
      artery injury induced by an external vascular cuff model. RESULTS: Three days
      post-injury, inflammatory cell infiltration increased significantly. Moreover,
      the percent positive area of tumor necrosis factor-alpha (TNF-alpha),
      intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1
      (VCAM-1) in media were higher in CuZnSOD(-/-) mice than in WT mice (TNF-alpha:
      34.8+/-8.4% versus 18.8+/-5.6%, p < 0.05, ICAM-1: 29.6+/-6.5% versus 11.0+/-2.8%,
      p < 0.05, VCAM-1: 23.5+/-7.5% versus 3.7+/-1.1%, p < 0.05). mRNA expression of
      iNOS was markedly increased in CuZnSOD(-/-) mice with cuff injury.
      Dihydroethidine staining revealed increased levels of vascular O(2)(-) in media
      from CuZnSOD(-/-) mice. Although neointimal formation remained unchanged, 14 days
      postinjury, we observed degeneration of the media, and the media/vessel wall
      ratio increased in CuZnSOD(-/-) mice (40.4+/-2.1% versus 26.8+/-1.4%, p < 0.05).
      Furthermore, SMemb/MHC-B-stained lesions increased markedly in CuZnSOD(-/-) mice.
      CONCLUSIONS: CuZnSOD-deficiency promoted inflammation, expressed adhesion
      molecules, and altered the structure of the media post-injury. Our results
      suggest that O(2)(-) participates importantly in the progression of early stage
      vascular inflammation, resulting in vascular remodeling in media but not
      neointimal formation, post-injury.

PMID- 21946536
TI  - Tumor suppressor BRCA1 epigenetically controls oncogenic microRNA-155.
AB  - BRCA1, a well-known tumor suppressor with multiple interacting partners, is
      predicted to have diverse biological functions. However, so far its only well
      established role is in the repair of damaged DNA and cell cycle regulation. In
      this regard, the etiopathological study of low-penetrant variants of BRCA1
      provides an opportunity to uncover its other physiologically important functions.
      Using this rationale, we studied the R1699Q variant of BRCA1, a potentially
      moderate-risk variant, and found that it does not impair DNA damage repair but
      abrogates the repression of microRNA-155 (miR-155), a bona fide oncomir.
      Mechanistically, we found that BRCA1 epigenetically represses miR-155 expression
      via its association with HDAC2, which deacetylates histones H2A and H3 on the miR
      155 promoter. We show that overexpression of miR-155 accelerates but the
      knockdown of miR-155 attenuates the growth of tumor cell lines in vivo. Our
      findings demonstrate a new mode of tumor suppression by BRCA1 and suggest that
      miR-155 is a potential therapeutic target for BRCA1-deficient tumors.

PMID- 21946537
TI  - Somatic deletions of genes regulating MSH2 protein stability cause DNA mismatch
      repair deficiency and drug resistance in human leukemia cells.
AB  - DNA mismatch repair enzymes (for example, MSH2) maintain genomic integrity, and
      their deficiency predisposes to several human cancers and to drug resistance. We
      found that leukemia cells from a substantial proportion of children (~11%) with
      newly diagnosed acute lymphoblastic leukemia have low or undetectable MSH2
      protein levels, despite abundant wild-type MSH2 mRNA. Leukemia cells with low
      levels of MSH2 contained partial or complete somatic deletions of one to four
      genes that regulate MSH2 degradation (FRAP1 (also known as MTOR), HERC1, PRKCZ
      and PIK3C2B); we also found these deletions in individuals with adult acute
      lymphoblastic leukemia (16%) and sporadic colorectal cancer (13.5%). Knockdown of
      these genes in human leukemia cells recapitulated the MSH2 protein deficiency by
      enhancing MSH2 degradation, leading to substantial reduction in DNA mismatch
      repair and increased resistance to thiopurines. These findings reveal a
      previously unrecognized mechanism whereby somatic deletions of genes regulating
      MSH2 degradation result in undetectable levels of MSH2 protein in leukemia cells,
      DNA mismatch repair deficiency and drug resistance.

PMID- 21946539
TI  - Expression of a mutant HSP110 sensitizes colorectal cancer cells to chemotherapy
      and improves disease prognosis.
AB  - Heat shock proteins (HSPs) are necessary for cancer cell survival. We identified
      a mutant of HSP110 (HSP110DeltaE9) in colorectal cancer showing microsatellite
      instability (MSI CRC), generated from an aberrantly spliced mRNA and lacking the
      HSP110 substrate-binding domain. This mutant was expressed at variable levels in
      almost all MSI CRC cell lines and primary tumors tested. HSP110DeltaE9 impaired
      both the normal cellular localization of HSP110 and its interaction with other
      HSPs, thus abrogating the chaperone activity and antiapoptotic function of HSP110
      in a dominant-negative manner. HSP110DeltaE9 overexpression caused the
      sensitization of cells to anticancer agents such as oxaliplatin and 5
      fluorouracil, which are routinely prescribed in the adjuvant treatment of people
      with CRC. The survival and response to chemotherapy of subjects with MSI CRCs was
      associated with the tumor expression level of HSP110DeltaE9. HSP110 may thus
      constitute a major determinant for both prognosis and treatment response in CRC.

PMID- 21946540
TI  - Characteristics of peripapillary retinal nerve fiber layer thickness in eyes with
      myopic optic disc tilt and rotation.
AB  - PURPOSE: The purpose of the study was to investigate the effects of myopic optic
      disc tilt and rotation on peripapillary retinal nerve fiber layer (RNFL)
      thickness characteristics measured by Cirrus HD spectral-domain optical coherence
      tomography (Cirrus HD OCT). METHODS: A total of 93 right eyes from 93 healthy
      young male individuals with myopia underwent ophthalmic examinations, including
      refractive error, axial length, and optic disc area measurements. The
      superior/inferior peak locations, RNFL thickness, and horizontal/vertical optic
      disc tilt were evaluated using the Cirrus HD OCT. The optic disc rotation was
      assessed by the angle between the long axis of the optic disc and the vertical
      meridian. The patients were divided into the tilted group and the non-tilted
      group; the tilted group was further divided into the rotated group and the
      nonrotated group. RESULTS: The eyes in the tilted group (n=47) had a greater
      axial length and thicker temporal RNFL and more temporally positioned
      superior/inferior peak locations than the non-tilted group (n=46) (all P <0.05).
      Among the eyes in the tilted group, the eyes in the rotated group (n=23) had a
      thicker temporal RNFL and a more temporally positioned superior peak location
      than the eyes in the nonrotated group (n=24) (all P <0.05). CONCLUSIONS: The eyes
      with a myopic temporal optic disc tilt and counterclockwise rotation had a
      thicker temporal RNFL and more temporally positioned superior peak location. The
      characteristics of the RNFL thickness in eyes with myopic optic disc tilt and
      rotation should be considered when interpreting the RNFL thickness measured by
      the Cirrus HD OCT.

PMID- 21946538
TI  - Epidermal growth factor receptor promotes glomerular injury and renal failure in
      rapidly progressive crescentic glomerulonephritis.
AB  - Rapidly progressive glomerulonephritis (RPGN) is a life-threatening clinical
      syndrome and a morphological manifestation of severe glomerular injury that is
      marked by a proliferative histological pattern ('crescents') with accumulation of
      T cells and macrophages and proliferation of intrinsic glomerular cells. We show
      de novo induction of heparin-binding epidermal growth factor-like growth factor
      (HB-EGF) in intrinsic glomerular epithelial cells (podocytes) from both mice and
      humans with RPGN. HB-EGF induction increases phosphorylation of the epidermal
      growth factor receptor (EGFR, also known as ErbB1) in mice with RPGN. In HB-EGF
      deficient mice, EGFR activation in glomeruli is absent and the course of RPGN is
      improved. Autocrine HB-EGF induces a phenotypic switch in podocytes in vitro.
      Conditional deletion of the Egfr gene from podocytes of mice alleviates the
      severity of RPGN. Likewise, pharmacological blockade of EGFR also improves the
      course of RPGN, even when started 4 d after the induction of experimental RPGN.
      This suggests that targeting the HB-EGF-EGFR pathway could also be beneficial in
      treatment of human RPGN.

PMID- 21946541
TI  - Morning dosing of once-daily glaucoma medication is more convenient and may lead
      to greater adherence than evening dosing.
AB  - PURPOSE: To determine if adherence and convenience of once-daily glaucoma
      medication is greater in the morning or the evening. DESIGN: Prospective,
      randomized crossover treatment trial. PATIENTS AND METHODS: Thirty patients newly
      diagnosed with glaucoma or ocular hypertension requiring intraocular pressure
      (IOP) reduction were started on travoprost eye drops and randomized to either
      morning or evening administration for 1 month. They were then crossed over to the
      opposite dosing schedule for the following month. Adherence was monitored using
      an automated dosing aid. MAIN OUTCOME MEASURES: Adherence was compared between
      morning versus evening dosing and first versus second month dosing. Demographic
      characteristics were obtained, treatment effect was measured, and patients
      completed a post-study questionnaire regarding the convenience of the 2 dosing
      regimens. RESULTS: Patient adherence overall was good (89.3%). There was no
      statistically significant difference (P=0.07) in adherence between morning dosing
      (90.9%) and evening dosing (87.3%). Adherence in the first month (91.7%) was
      superior to the second month (86.5%). There was no significant difference in IOP
      response between morning and evening dosing. Patients found morning dosing more
      convenient than evening dosing. CONCLUSIONS: Early adherence to treatment with a
      prostaglandin analogue is good, but patients prefer morning administration to
      evening administration. This may lead to greater adherence with morning
      administration, particularly among men. Adherence decreases from the first to
      second month after initiation of treatment. IOP response to this treatment is not
      significantly affected by morning versus evening administration.

PMID- 21946542
TI  - Inter-examiner reproducibility of Ocular Response Analyzer using the waveform
      score quality index in healthy subjects.
AB  - PURPOSE: To evaluate the inter-examiner reproducibility of Ocular Response
      Analyzer (ORA) parameters in healthy subjects using the waveform score (WS) for
      quality control of acquisition. PATIENTS AND METHODS: Fifteen healthy subjects
      had their intraocular pressure (IOP) measured with ORA by 2 masked examiners. An
      acquisition protocol that aimed at obtaining 4 reliable measurements in each eye
      with WS>=6 and with as few repeated measurements as possible was employed,
      whereas a maximum of 8 measurements per eye was allowed. Additional good quality
      criteria included symmetrical force-in and force-out applanation signal peaks on
      the ORA waveform and few or no distortions of the applanation signal curve. Only
      the right eyes were included in the analysis. Examiners were trained but not
      experienced. The inter-examiner reproducibility of ORA parameters was assessed
      using the intraclass correlation coefficient (ICC). Mean values of the best 4
      measurements were considered in analysis. RESULTS: ICC including the best 4
      measurements per eye was high for all ORA parameters. Specifically, ICC for
      Goldmann-correlated IOP was 0.961, for corneal-compensated IOP was 0.962, for
      corneal resistance factor was 0.987, and for corneal hysteresis was 0.988.
      Similar reproducibility was found when only the 3 best measurements per eye were
      included in the analysis. CONCLUSIONS: The protocol for IOP measurement with ORA
      using the WS >=6 as quality index achieved high inter-examiner reproducibility
      for all ORA parameters. High reproducibility was obtained even by inexperienced
      examiners when considering the mean of the best 3 measurements per eye.

PMID- 21946543
TI  - Comparison of optic disc topography in the cases with graves disease and healthy
      controls.
AB  - PURPOSE: To compare the optic nerve head topographic parameters of the cases with
      Graves disease (GD), and the age and sex-matched control group, by using
      Heidelberg retinal tomography III. MATERIALS AND METHODS: We evaluated both eyes
      of 65 patients with GD and 54 age and sex-matched controls. For statistical
      analysis, Mann-Whitney U test and independent sample t test were used.
      Statistical significance was set as P < 0.05. RESULTS: The study group consisted
      of 22 male (33.8%) and 43 female (66.2%) GD cases with a mean age of 40.3 +/-
      11.9 years and the control group consisted of 26 male (48.1%) and 28 female
      (51.9%) healthy controls with a mean age of 36.9 +/- 7.6 years. The differences
      between the age and sexes of the groups were not statistically significant (P =
      0.07 and P = 0.11, respectively). The mean intraocular pressure of the study
      group was 14.6 +/- 2.9 mm Hg (range, 8 to 20 mm Hg), whereas in the control
      group, it was 13.4 +/- 2.1 mm Hg (range, 10 to 19 mm Hg). The difference between
      the intraocular pressures was statistically significant (P = 0.01). The mean
      retinal nerve fiber layer (RNFL) thickness (0.31 +/- 0.08 mm) and the mean RNFL
      cross-sectional area (1.5 +/- 0.43 mm) of the control group were greater than the
      mean RNFL thickness (0.25 +/- 0.06 mm) and the mean RNFL cross-sectional area
      (1.30 +/- 0.32 mm) of the study group (P = 0.02, P = 0.03 respectively).
      CONCLUSIONS: This result suggests that patients with GD may have thinner RNFL
      than healthy controls.

PMID- 21946544
TI  - Association between plasma endothelin-1 and severity of different types of
      glaucoma.
AB  - PURPOSE: Endothelin-1 (ET-1) has been suggested to play an important role in the
      pathogenesis of glaucoma. Herein, we studied whether increased levels of plasma
      ET-1 are associated with changes in the visual field and changes in optical
      coherence tomography (OCT)-measured retinal nerve fiber layer (RNFL) thickness in
      patients with different types of glaucoma. PATIENTS AND METHODS: : Plasma
      concentration of ET-1 was determined in 31 patients with primary open-angle
      glaucoma, 18 patients with normal tension glaucoma, 16 patients with primary
      angle-closure glaucoma, and in 37 normal controls. In all participants, visual
      field testing was performed and OCT was used to measure RNFL thickness. The
      correlation between mean ET-1 level and changes in the visual field (mean
      deviation, dB) and changes in OCT-measured RNFL thickness in 1 randomly selected
      eye from each patient in each group was then evaluated. RESULTS: The ET-1 level
      was 3.27+/-1.25 pg/mL in the primary open-angle glaucoma group (-14.09+/-8.76
      dB), 3.12+/-1.46 pg/mL in the normal tension glaucoma group (-8.87+/-6.15 dB),
      2.58+/-.22pg/mL in the primary angle-closure glaucoma group (-14.55+/-10.2 dB),
      and 1.53+/-1.49 pg/mL in the control group. Although mean ET-1 levels were
      significantly higher in all 3 of the glaucoma groups than in the control group,
      there was no significant difference in ET-1 level among the 3 glaucoma groups. In
      addition, no significant correlation was found between levels of plasma ET-1 and
      structural or functional changes in patients with different types of glaucoma.
      CONCLUSIONS: : There was no correlation between plasma levels of ET-1 and
      severity of glaucoma. The role ET-1 plays in the pathogenesis of glaucoma remains
      to be determined.

PMID- 21946545
TI  - Intraocular pressure: Goldmann tonometry, computational model, and calibration
      equation.
AB  - PURPOSE: There exists a concern about the general accuracy of intraocular
      pressure (IOP) measurements using tonometry, and especially Goldmann applanation
      tonometer (GAT) because it considers the cornea as an infinite thin shell. In
      this study, the relationship between the true IOP and tonometric IOP, external
      curvature radius (ECR), and central corneal thickness (CCT) is explored. METHODS:
      In this study, the calibration of the IOP measurements through GAT for different
      values of CCT, ECR, and E (Young modulus), is done through computational
      simulations of the mechanical behavior of the cornea subjected to the applanation
      process using the finite element method (FEM). Previous to this simulations,
      experimentations on rabbits were performed to confirm that inaccurate readings
      are obtained with GAT in certain conditions. This methodology is also followed to
      establish the range of corneal parameters of patients for which the GAT measure
      of pressure is reliable. The calibration equation for GAT measurements is
      developed from a statistical multiple linear regression analysis. RESULTS: Based
      on a statistical variable analysis of the computational modeling results, a
      calibration equation is established for the GAT that relates the true IOP with
      the ECR, CCT, and GAT measurements. CONCLUSIONS: Our results show that GAT
      measures are linearly dependent on the modulus of elasticity of the cornea;
      nevertheless, if we consider a healthy cornea with a specific modulus of
      elasticity, it is possible to correct the measure with a linear equation
      involving CCT and ECR.

PMID- 21946546
TI  - Ibopamine: D1-dopaminergic agonist in the diagnosis of glaucoma.
AB  - PURPOSE: The purpose of the study was to assess the effect of ibopamine (3,4 di
      isobutyrrylester of N-methyldopamine), a D1-dopamine agonist, on intraocular
      pressure (IOP) in offspring of parents with primary openangle glaucoma as a
      consequence of outflow structures impairment. MATERIALS AND METHODS: We included
      participants aged between 8 and 40 years: group 1, 163 offspring of at least 1
      parent with primary openangle glaucoma with normal IOP and without glaucomatous
      damages; group 2, 108 offspring of healthy parents (without history or existing
      glaucoma). Ibopamine test was performed by instilling 2 drops, 5 minutes apart,
      in both eyes followed by repeated IOP measurements over a 45-minute period. The
      test is considered positive if there is an IOP increase of >=3 mm Hg 45 minutes
      after instillation. RESULTS: Baseline IOP before the test was 15.73+/-2.31 and
      15.31+/-1.86 mm Hg in groups 1 and 2, respectively. Test was positive in 44.33%
      of cases in group 1 with a mean increase in IOP of 5.57 mm Hg (P<0.001), whereas
      in all participants of group 2 the test was negative with even 1 to 2 mm Hg IOP
      reduction. CONCLUSIONS: D1-dopaminergic stimulation due to ibopamine increases
      IOP as a result of increased production of the aqueous humor in participants with
      an impaired outflow. The study showed that offspring of at least 1 parent with
      primary openangle glaucoma--offspring without glaucomatous damages--show an
      increase of IOP after ibopamine administration, which signifies an impaired
      function of outflow structures and, therefore, a predisposition to intraocular
      hypertension and possible glaucoma.

PMID- 21946547
TI  - Fixation behavior in primary open angle glaucoma at early and moderate stage
      assessed by the MicroPerimeter MP-1.
AB  - PURPOSE: Using MicroPerimetry MP-1 to assess the fixation behavior in early and
      moderate primary open angle glaucoma (POAG). METHODS: Thirty-nine early and
      moderate POAG eyes and 22 normal eyes were enrolled prospectively. The stability
      and location of the fixation in each subject eye were recorded by the macula 10
      degree program of the microperimeter (MP-1). Retinal sensitivity was examined
      using the G2 program phase 1 of an Octopus 101 perimeter and the macula 10-degree
      program of the MP-1. The fixation behavior and the retinal sensitivity were
      compared between POAG and control groups. The correlation between the fixation
      behavior and the retinal sensitivity was analyzed in POAG patients. RESULTS: :
      Fixation instability was detected in POAG (P=0.016). It correlated with the mean
      defect on Octopus perimeter and all the mean macular sensitivity parameters of MP
      1, which includes the central 10 degrees (r=0.416, P=0.008), 6 degrees (r=0.401,
      P=0.011), 2 degrees (r=0.376, P=0.018), inferotemporal (r=0.399, P=0.012) and
      inferonasal (r=0.387, P=0.015) quadrants of the central 6 degrees. All the POAG
      patients had a predominantly central fixation. CONCLUSION: Fixation instability
      manifested in early and moderate POAG eyes, which may be an early sign of POAG.

PMID- 21946548
TI  - A short-term randomized clinical trial of daily versus alternate day use of
      travoprost 0.004% in the treatment of ocular hypertension.
AB  - PURPOSE: To compare the daily versus the alternate day use of travoprost 0.004%
      in lowering the intraocular pressure (IOP) in patients with ocular hypertension.
      METHODS: Fourteen patients with ocular hypertension in both eyes have been
      randomly assigned to receive travoprost 0.004% once a day in 1 eye and once every
      other day in the other eye. The main outcome measure was change in the mean of
      the IOPs measured at 9:00 AM, and 4:00 PM between baseline (before treatment) and
      measurement of IOPs at 1, 2, 4, 8, and 12 weeks after treatment. RESULTS: After 3
      months of treatment, daily use of travoprost 0.004% significantly reduced IOP
      (mean+/-standard error of mean) by 6.1+/-0.5 mmHg (P<0.001) and alternate day use
      by 5.9+/-0.3 mmHg (P< 0.001) adjusted from an overall baseline of 24.3+/-0.5 mm
      Hg. The difference in the IOP-lowering effect was not statistically significant
      (P<0.05). CONCLUSIONS: Alternate day use of travoprost 0.004% was as safe and
      effective as its daily use in lowering the IOP in patients with ocular
      hypertension.

PMID- 21946549
TI  - Correction factors for Goldmann Tonometry.
AB  - PURPOSE: The purpose of the study was to evaluate the in vitro accuracy of
      correction factors in decreasing the error in the intraocular pressure (IOP)
      measurements obtained using the Goldmann Applanation Tonometer (GAT). METHODS:
      Nineteen donor corneas, from individuals aged between 57 and 99 years (mean 75.7
      years, standard deviation+/-11.4 years) were subjected to posterior pressure
      simulating in vivo true IOP (IOPT) using an inflation test rig. Central corneal
      thickness and corneal curvature were measured. The posterior pressure was set at
      25 different pressure levels between 5 and 45 mm Hg and IOP was measured using
      the GAT. Five different correction equations were applied to the IOP measurements
      obtained using the GAT to determine corrected IOP. The multiparameter correction
      equations applied were derived by Elsheikh, Ehlers, Chihara, Shimmyo et al, and
      Orssengo and Pye. The differences between IOPT and the IOP measured using the GAT
      were recorded as uncorrected errors, whereas the differences between IOPT and
      each of the corrected IOP were the tonometry errors after correction. RESULTS:
      The mean and standard deviation of error in tonometry before correction was
      +2.25+/-0.62 mm Hg. The mean errors in tonometry after correction using the
      Elsheikh and Chihara equations were +0.78+/-0.62 and +1.08+/-0.61 mm Hg,
      respectively. The mean errors in tonometry for the Ehlers, Shimmyo et al, and
      Orssengo and Pye equations were negative, indicating an overcorrection; the
      values were -0.75+/-2.28, -1.27+/-1.85, and -0.77+/-1.83 mm Hg, respectively.
      CONCLUSIONS: The Elsheikh and the Chihara et al's equations considerably
      decreased error in IOP measurements obtained by the GAT when compared with IOPT
      and were more consistent than other correction equations. The 2 equations may be
      of clinical utility in obtaining estimates of IOPT.

PMID- 21946550
TI  - Aqueous vascular endothelial growth factor and endothelin-1 levels in branch
      retinal vein occlusion associated with normal tension glaucoma.
AB  - PURPOSE: To evaluate aqueous levels of vascular endothelial growth factor (VEGF)
      and endothelin-1 (ET-1) in patients with branch retinal vein occlusion (BRVO)
      with and without normal tension glaucoma (NTG), and to assess the therapeutic
      efficacy of intravitreal bevacizumab (IVB) in these patients. METHODS: Sixteen
      eyes with NTG of 48 age and sex-matched eyes without NTG that had previously
      received IVB for BRVO were followed for 6 months. Aqueous VEGF and ET-1 levels
      were measured by enzyme-linked immunosorbent assay at the time of baseline IVB.
      Logarithm of the minimum angle of resolution best corrected visual acuity (BCVA)
      and central macular thickness (CMT) were measured at baseline and then at 1, 3,
      and 6 months postinjection. RESULTS: The obstruction site of BRVO was closer to
      the optic disk in eyes with NTG compared with controls (P=0.001). Baseline BCVA,
      CMT, and VEGF levels were similar between the 2 groups. Baseline ET-1 levels were
      significantly higher in eyes with NTG than those without NTG (P=0.009). After
      IVB, there was a significant improvement in both BCVA and CMT at 6 months,
      irrespective of the presence of NTG. However, BCVA in the presence of NTG was
      significantly worse at 6 months compared with eyes without NTG even though CMT
      was similarly reduced in both groups (P=0.04). CONCLUSIONS: Aqueous VEGF levels
      are similar in patients with BRVO with or without NTG, whereas aqueous ET-1
      levels are elevated in the presence of NTG. Although IVB may be effective in the
      treatment of BRVO, the presence of NTG may limit visual recovery despite anatomic
      recovery of CMT.

PMID- 21946551
TI  - Digital versus film stereo-photography for assessment of the optic nerve head in
      glaucoma and glaucoma suspect patients.
AB  - PURPOSE: One of the leading methods for optic nerve head assessment in glaucoma
      remains stereoscopic photography. This study compared conventional film and
      digital stereoscopy in the quantitative and qualitative assessment of the optic
      nerve head in glaucoma and glaucoma suspect patients. METHODS: Fifty patients
      with glaucoma or suspected glaucoma underwent stereoscopic photography of the
      optic nerve head with a 35-mm color slide film and a digital camera.
      Photographs/images were presented in random order to 3 glaucoma specialists for
      independent analysis using a standardized assessment form. Findings for the
      following parameters were compared among assessors and between techniques:
      cup/disc (C/D) ratio, state of the optic rim, presence of peripapillary atrophy
      and appearance of the retinal nerve fiber layer, blood vessels, and lamina
      cribrosa. The film-based and image-based diagnoses (glaucoma yes/no) were
      compared as well. RESULTS: Despite high level of agreement across graders using
      the same method for the horizontal and vertical C/D ratio, (intraclass
      correlations 0.80 to 0.83), the agreement across graders was much lower for the
      other parameters using the same method. Similarly the agreement between the
      findings of the same grader using either method was high for horizontal and
      vertical C/D ratio, but low for the other parameters. The latter differences were
      reflected in the disagreement regarding the final diagnosis: The diagnoses
      differed by technique for each grader in 18% to 46% of eyes, resulting in 38.5%
      of eyes diagnosed with glaucoma by film photography that "lost" their diagnosis
      on the digital images, whereas 18.7% of eyes diagnosed as nonglaucomatous by film
      photography were considered to have glaucoma on the digital images. CONCLUSIONS:
      Although there is consistency between 35-mm film stereoscopy and digital
      stereoscopy in determining the cup/disc (C/D) ratio, in all other parameters
      large differences exist, leading to differences in diagnosis. Differences in
      capturing images between digital and film photography may lead to loss of
      information and misdiagnosis. Further studies are needed to determine the
      reliability of the new digital techniques.

PMID- 21946552
TI  - Effect of cataract extraction on Visual Field Index in glaucoma.
AB  - PURPOSE: : To determine the effect of cataract on the Visual Field Index (VFI) in
      glaucoma patients. METHODS: : Reliable visual fields (VFs) of 53 patients (53
      eyes) with primary glaucoma who underwent phacoemulsification either alone or
      combined with trabeculectomy were analyzed before and after surgery. All patients
      had VFs within a period of 15 months before and after surgery. VFI, mean
      deviation (MD), and pattern standard deviation (PSD) before surgery were compared
      with those after surgery. RESULTS: : Median (25th and 75th percentiles) MD after
      cataract surgery [-10.52 dB (range, -19.25 to -4.86 dB)] was significantly better
      (P=0.003) than that before surgery [-11.74 dB (range, -20.61 to -7.15 dB)].
      Median PSD after surgery [4.76 dB (range, 2.48 to 9.83)] was worse (P=0.01) than
      that before surgery [3.50 dB (range, 1.93 to 8.20 dB)] when eyes with MD better
      than -20 dB were considered (41 eyes). VFI after surgery [80% (range, 44% to
      94%)] was similar (P=0.92) to that before surgery [77% (range, 37% to 92%)]. MD
      improved while VFI remained unchanged in both nuclear sclerotic (n=41) and
      posterior subcapsular cataracts (n=12). CONCLUSIONS: : MD and PSD were
      significantly affected, whereas VFI was not affected by cataract. VFI may be a
      more robust measure of VF damage than MD or PSD in glaucomatous eyes with
      coexisting cataracts.

PMID- 21946554
TI  - American Glaucoma Society Position Statement: electronic data standards for
      clinical practice.

PMID- 21946553
TI  - Prevention of ocular scarring after glaucoma filtering surgery using the
      monoclonal antibody LT1009 (Sonepcizumab) in a rabbit model.
AB  - PURPOSE: Excessive scarring leading to failure of the filtering bleb continues to
      be a major problem after glaucoma filtration surgery. This study examines the
      antifibrotic effects of the anti-S1P monoclonal antibody LT1009 (Sonepcizumab) in
      prolonging bleb survival in a rabbit model of glaucoma filtering surgery.
      METHODS: The frequency of LT1009 dosage was determined initially using an enzyme
      linked immunosorbent assay assay measuring LT1009 eye tissue retention in 6 New
      Zealand White rabbits. A further 21 New Zealand White rabbits underwent glaucoma
      filtering surgery. Bleb tissues were observed and compared clinically and
      histologically. The duration of bleb elevation was compared among LT1009,
      balanced saline solution (BSS) negative control, and mitomycin-C (MMC)-positive
      control. RESULTS: The mean duration of bleb survival was 28.5+/-8.5 days for
      rabbits receiving injections of LT1009, 21.0+/-5.6 days for those receiving
      injections of BSS, and 33.8+/-5.6 days for rabbits receiving MMC. Analysis of
      variance with post hoc testing suggests a statistically significant trend of
      improvement in bleb duration for LT1009 when compared with BSS controls.
      Nonpainful, upper eyelid edema was noted after 5 injections of LT1009, which
      resolved over a 10-day period. MMC eyes developed avascular conjunctivas with
      areas of thinning and sparse cellularity, whereas the conjunctiva of LT1009 and
      BSS eyes remained relatively normal. CONCLUSIONS: The monoclonal antibody LT1009
      demonstrated a longer duration of bleb elevation than BSS control without adverse
      conjunctival effects associated with MMC. However, after multiple doses LT1009
      use was associated with short-term upper eyelid edema.

PMID- 21946555
TI  - Optic disc cupping associated with neurosyphilis.

PMID- 21946556
TI  - Quantification of retinal nerve fiber layer thickness after unilateral acute
      primary angle closure in Asian Indian eyes.
AB  - PURPOSE: To determine retinal nerve fiber layer thickness (RNFLT) using Spectral
      optical coherence tomography/scanning laser ophthalmoscope (Spectral OCT/SLO) in
      Asian Indian eyes after single, unilateral attack of acute primary angle closure
      (APAC). METHODS: Thirty-two patients with unilateral attack of APAC with normal
      optic disc and normal visual field, unaffected fellow eyes, and 35 age-matched
      normal control eyes were enrolled for the study. Six weeks after the remission of
      acute attack, peripapillary average, quadrant, and clock-hour RNFLT were compared
      between 3 groups using Spectral OCT/SLO. RESULTS: APAC patients had mean IOP of
      51.3+/-13.3 mm Hg (range, 40-74) at the time of presentation with acute attack in
      the affected eye and 14.9+/-2.9 mm Hg at 6 weeks after resolution of APAC.
      Duration of symptoms of acute attack was 35.9+/-23.8 hours. Significant
      differences were found between RNFLT in APAC and fellow eyes for most the
      parameters except for 1, 4, 6, and 7-o'clock-hour sector. Most of the RNFLT
      parameters showed statistically significant difference between APAC and normal
      control eyes except for temporal quadrant, 6, 7-o'clock-hour sectors.
      Statistically significant differences were found between RNFLT in unaffected
      fellow and normal control eyes for most of the parameters except for 6, 7, 11
      o'clock-hour sectors. CONCLUSIONS: RNFLT was found to be significantly thinner in
      APAC and unaffected fellow eyes when compared with normal age-matched controls.
      Hence, patients with APAC should be monitored carefully to determine its long
      term effects on optic disc, RNFLT, and visual fields. Longitudinal studies can
      determine whether the RNFLT measurements remained stable or showed progression in
      these patients.

PMID- 21946557
TI  - Circumferential trabeculotomy with an illuminated microcatheter in congenital
      glaucomas.
AB  - PURPOSE: To determine the safety and efficacy of circumferential trabeculotomy
      for congenital glaucomas using an illuminated microcatheter. METHODS: This was a
      retrospective chart study involving 11 eyes from 7 patients with primary or
      secondary congenital or juvenile glaucoma who underwent circumferential
      trabeculotomy performed with an illuminated microcatheter over a 2-year period.
      Data from eyes with 6 or more months of follow-up intraocular pressure (IOP) data
      were included in the analysis. Mean IOP was determined along with a survival
      analysis. Unqualified success was defined as an IOP<21 mm Hg and at least a 30%
      reduction in IOP without the use of IOP-lowering agents and a qualified success
      when medications were needed to reach this goal. RESULTS: Mean IOP (mm Hg) was
      reduced from 33.8+/-6.3 preoperatively to 18.3+/-3.5 at the final postoperative
      visit (P-value<0.001). Length of follow-up was 8 to 12 months (mean of 11 mo). A
      qualified success was seen in 90.1% of eyes and an unqualified success in 81.8%.
      If eyes with previous angle surgery were excluded, the unqualified success was
      87.5% and the qualified success was 100%. Transient hyphema was seen in all
      cases. No long-term surgical complications were seen. CONCLUSIONS:
      Circumferential trabeculotomy performed with an illuminated microcatheter
      provided significant IOP lowering in all patients with unqualified success in the
      majority of eyes and no significant complications. Further study with even longer
      follow-up is needed.

PMID- 21946558
TI  - Iron and ROS control of the DownSTream mRNA decay pathway is essential for plant
      fitness.
AB  - A new regulatory pathway involved in plant response to oxidative stress was
      revealed using the iron-induced Arabidopsis ferritin AtFER1 as a model. Using
      pharmacological and genetic approaches, the DownSTream (DST) cis-acting element
      in the 3'-untranslated region of the AtFER1 mRNA was shown to be involved in the
      degradation of this transcript, and oxidative stress triggers this
      destabilization. In the two previously identified trans-acting mutants (dst1 and
      dst2), AtFER1 mRNA stability is indeed impaired. Other iron-regulated genes
      containing putative DST sequences also displayed altered expression. Further
      physiological characterization identified this oxidative stress-induced DST
      dependent degradation pathway as an essential regulatory mechanism to modulate
      mRNA accumulation patterns. Alteration of this control dramatically impacts plant
      oxidative physiology and growth. In conclusion, the DST-dependent mRNA stability
      control appears to be an essential mechanism that allows plants to cope with
      adverse environmental conditions.

PMID- 21946559
TI  - Structural basis for cell surface patterning through NetrinG-NGL interactions.
AB  - Brain wiring depends on cells making highly localized and selective connections
      through surface protein-protein interactions, including those between NetrinGs
      and NetrinG ligands (NGLs). The NetrinGs are members of the structurally
      uncharacterized netrin family. We present a comprehensive crystallographic
      analysis comprising NetrinG1-NGL1 and NetrinG2-NGL2 complexes, unliganded
      NetrinG2 and NGL3. Cognate NetrinG-NGL interactions depend on three specificity
      conferring NetrinG loops, clasped tightly by matching NGL surfaces. We engineered
      these NGL surfaces to implant custom-made affinities for NetrinG1 and NetrinG2.
      In a cellular patterning assay, we demonstrate that NetrinG-binding selectivity
      can direct the sorting of a mixed population of NGLs into discrete cell surface
      subdomains. These results provide a molecular model for selectivity-based
      patterning in a neuronal recognition system, dysregulation of which is associated
      with severe neuropsychological disorders.

PMID- 21946560
TI  - Dpb11 coordinates Mec1 kinase activation with cell cycle-regulated Rad9
      recruitment.
AB  - Eukaryotic cells respond to DNA damage by activating checkpoint signalling
      pathways. Checkpoint signals are transduced by a protein kinase cascade that also
      requires non-kinase mediator proteins. One such mediator is the Saccharomyces
      cerevisiae Dpb11 protein, which binds to and activates the apical checkpoint
      kinase, Mec1. Here, we show that a ternary complex of Dpb11, Mec1 and another key
      mediator protein Rad9 is required for efficient Rad9 phosphorylation by Mec1 in
      vitro, and for checkpoint activation in vivo. Phosphorylation of Rad9 by cyclin
      dependent kinase (CDK) on two key residues generates a binding site for tandem
      BRCT repeats of Dpb11, and is thereby required for Rad9 recruitment into the
      ternary complex. Checkpoint signalling via Dpb11, therefore, does not efficiently
      occur during G1 phase when CDK is inactive. Thus, Dpb11 coordinates checkpoint
      signal transduction both temporally and spatially, ensuring the initiator kinase
      is specifically activated in proximity of one of its critical substrates.

PMID- 21946561
TI  - NYAP: a phosphoprotein family that links PI3K to WAVE1 signalling in neurons.
AB  - The phosphoinositide 3-kinase (PI3K) pathway has been extensively studied in
      neuronal function and morphogenesis. However, the precise molecular mechanisms of
      PI3K activation and its downstream signalling in neurons remain elusive. Here, we
      report the identification of the Neuronal tYrosine-phosphorylated Adaptor for the
      PI 3-kinase (NYAP) family of phosphoproteins, which is composed of NYAP1, NYAP2,
      and Myosin16/NYAP3. The NYAPs are expressed predominantly in developing neurons.
      Upon stimulation with Contactin5, the NYAPs are tyrosine phosphorylated by Fyn.
      Phosphorylated NYAPs interact with PI3K p85 and activate PI3K, Akt, and Rac1.
      Moreover, the NYAPs interact with the WAVE1 complex which mediates remodelling of
      the actin cytoskeleton after activation by PI3K-produced PIP(3) and Rac1. By
      simultaneously interacting with PI3K and the WAVE1 complex, the NYAPs bridge a
      PI3K-WAVE1 association. Disruption of the NYAP genes in mice affects brain size
      and neurite elongation. In conclusion, the NYAPs activate PI3K and concomitantly
      recruit the downstream effector WAVE complex to the close vicinity of PI3K and
      regulate neuronal morphogenesis.

PMID- 21946562
TI  - microRNA-34c is a novel target to treat dementias.
AB  - MicroRNAs are key regulators of transcriptome plasticity and have been implicated
      with the pathogenesis of brain diseases. Here, we employed massive parallel
      sequencing and provide, at an unprecedented depth, the complete and quantitative
      miRNAome of the mouse hippocampus, the prime target of neurodegenerative diseases
      such as Alzheimer's disease (AD). Using integrative genetics, we identify miR-34c
      as a negative constraint of memory consolidation and show that miR-34c levels are
      elevated in the hippocampus of AD patients and corresponding mouse models. In
      line with this, targeting miR-34 seed rescues learning ability in these mouse
      models. Our data suggest that miR-34c could be a marker for the onset of
      cognitive disturbances linked to AD and indicate that targeting miR-34c could be
      a suitable therapy.

PMID- 21946564
TI  - Adaptive kernel independent component analysis and UV spectrometry applied to
      characterize the procedure for processing prepared rhubarb roots.
AB  - By determination of the number of absorptive chemical components (ACCs) in
      mixtures using median absolute deviation (MAD) analysis and extraction of
      spectral profiles of ACCs using kernel independent component analysis (KICA), an
      adaptive KICA (AKICA) algorithm was proposed. The proposed AKICA algorithm was
      used to characterize the procedure for processing prepared rhubarb roots by
      resolution of the measured mixed raw UV spectra of the rhubarb samples that were
      collected at different steaming intervals. The results show that the spectral
      features of ACCs in the mixtures can be directly estimated without chemical and
      physical pre-separation and other prior information. The estimated three
      independent components (ICs) represent different chemical components in the
      mixtures, which are mainly polysaccharides (IC1), tannin (IC2), and anthraquinone
      glycosides (IC3). The variations of the relative concentrations of the ICs can
      account for the chemical and physical changes during the processing procedure:
      IC1 increases significantly before the first 5 h, and is nearly invariant after 6
      h; IC2 has no significant changes or is slightly decreased during the processing
      procedure; IC3 decreases significantly before the first 5 h and decreases
      slightly after 6 h. The changes of IC1 can explain why the colour became black
      and darkened during the processing procedure, and the changes of IC3 can explain
      why the processing procedure can reduce the bitter and dry taste of the rhubarb
      roots. The endpoint of the processing procedure can be determined as 5-6 h, when
      the increasing or decreasing trends of the estimated ICs are insignificant. The
      AKICA-UV method provides an alternative approach for the characterization of the
      processing procedure of rhubarb roots preparation, and provides a novel way for
      determination of the endpoint of the traditional Chinese medicine (TCM)
      processing procedure by inspection of the change trends of the ICs.

PMID- 21946563
TI  - Regulation of integrin affinity on cell surfaces.
AB  - Lymphocyte activation triggers adhesiveness of lymphocyte function-associated
      antigen-1 (LFA-1; integrin alpha(L)beta(2)) for intercellular adhesion molecules
      (ICAMs) on endothelia or antigen-presenting cells. Whether the activation signal,
      after transmission through multiple domains to the ligand-binding alphaI domain,
      results in affinity changes for ligand has been hotly debated. Here, we present
      the first comprehensive measurements of LFA-1 affinities on T lymphocytes for
      ICAM-1 under a broad array of activating conditions. Only a modest increase in
      affinity for soluble ligand was detected after activation by chemokine or T-cell
      receptor ligation, conditions that primed LFA-1 and robustly induced lymphocyte
      adhesion to ICAM-1 substrates. By stabilizing well-defined LFA-1 conformations by
      Fab, we demonstrate the absolute requirement of the open LFA-1 headpiece for
      adhesiveness and high affinity. Interaction of primed LFA-1 with immobilized but
      not soluble ICAM-1 triggers energy-dependent affinity maturation of LFA-1 to an
      adhesive, high affinity state. Our results lend support to the traction or
      translational motion dependence of integrin activation.

PMID- 21946565
TI  - Mitochondrial dysfunction resulting from the absence of mitochondrial porin in
      Neurospora crassa.
AB  - Porin, the voltage-dependent anion-selective channel (VDAC) in the mitochondrial
      outer membrane, contributes to metabolism and apoptosis. VDAC function was
      investigated in Neurospora, an obligate aerobe with a single porin. Porinless
      strains are viable, with cold-sensitive growth, cytochrome deficiencies and
      overexpression of alternative oxidase. iTRAQ labeling of mitochondria from a
      porinless strain and its progenitor revealed a small group of proteins with
      altered expression levels in the mutant organelles. Porinless Neurospora appears
      to compensate not by inducing alternative pores, but by altering electron flow
      and nucleotide metabolism. Transcriptional and post-transcriptional mechanisms
      contribute to the response, reflecting the extent of porin influence.

PMID- 21946566
TI  - Large scale mtDNA sequencing reveals sequence and functional conservation as
      major determinants of homoplasmic mtDNA variant distribution.
AB  - The mitochondrial DNA (mtDNA) is highly variable, containing large numbers of
      pathogenic mutations and neutral polymorphisms. The spectrum of homoplasmic mtDNA
      variation was characterized in 730 subjects and compared with known pathogenic
      sites. The frequency and distribution of variants in protein coding genes were
      inversely correlated with conservation at the amino acid level. Analysis of tRNA
      secondary structures indicated a preference of variants for the loops and some
      acceptor stem positions. This comprehensive overview of mtDNA variants
      distinguishes between regions and positions which are likely not critical, mainly
      conserved regions with pathogenic mutations and essential regions containing no
      mutations at all.

PMID- 21946567
TI  - Agreement in the classification and treatment of the superior labrum.
AB  - BACKGROUND: The Snyder classification scheme is the most commonly used system for
      classifying superior labral injuries. Although this scheme is intended to be used
      for arthroscopic visual classification only, it is thought that other
      nonarthroscopic historical variables also influence the classification. PURPOSE:
      This study was conducted to evaluate the intrasurgeon and intersurgeon agreement
      in classifying variable presentations of the superior labrum and to evaluate the
      influence of clinical variables on the classification and treatment choices of
      surgeons. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 3. METHODS:
      A group of arthroscopic shoulder surgeons were asked to rank in order of
      importance clinical variables considered in diagnosing and treating the superior
      labrum. The surgeons then watched 50 arthroscopic videos of the superior labrum,
      ranging from normal to pathologic, on 3 different occasions. The first and third
      viewings were accompanied by no clinical information. The second viewing was
      accompanied by a detailed clinical vignette for each video. The surgeons selected
      a classification and treatment for each video. RESULTS: A patient's job/sport,
      age, and physical examination findings were considered the most important
      clinical variables surgeons consider during management of the superior labrum.
      Comparing the 2 viewings without clinical information, surgeons selected a
      different classification 28.5% of the time from the first to the second time. A
      different classification was chosen 71.5% of the time when the surgeon was
      supplied a clinical vignette at the subsequent viewing. Similarly, the treatment
      selected changed in 36% and 69.1% of cases when viewed again without vignettes
      and with vignettes, respectively. Intersurgeon agreement was moderate without
      clinical vignettes and fair with vignettes. Historical, physical examination, and
      surgical observations were found to influence the odds of change of
      classification. CONCLUSION: There is significant intrasurgeon and intersurgeon
      variability in classification and treatment of the superior labrum. Clinical
      historical, examination, and surgical findings influence classification and
      treatment choices.

PMID- 21946568
TI  - Oxidation as "the stress of life".
AB  - Multiple biological consequences of oxidative stress are known to contribute to
      aging and aging-related pathologies. It was recently shown that
      (carboxyalkyl)pyrroles (CAPs), the end products of phospholipid oxidation serve
      as a novel class of endogenous ligands for Toll-like receptors (TLRs) and promote
      the process of angiogenesis. In this review, we discuss implications of these
      findings in the context of age-related pathologies, including tumorigenesis.
      Accumulation of oxidation products in tissues of aging organisms might create
      conditions for uncontrolled pathological angiogenesis as seen in patients with
      age related macular degeneration. CAPs and their receptors, TLRs might also
      promote the progression of atherosclerotic lesions. Importantly, besides their
      role in a number of pathologies, oxidative products of phospholipids contribute
      to tissue repair processes thereby antagonizing the destructive effects of
      oxidation.

PMID- 21946570
TI  - Reflections.

PMID- 21946569
TI  - MRE11 and ATM AKTivate pro-survival signaling.

PMID- 21946571
TI  - Postoperative pain--underestimated and undertreated.

PMID- 21946572
TI  - [What knowledge about knowledge?].

PMID- 21946573
TI  - [System errors in Norwegian health care].

PMID- 21946574
TI  - [Stroke units and mortality].

PMID- 21946576
TI  - [Child psychiatric disorders and "kiss-kid"].

PMID- 21946577
TI  - [Norwegian doctors and humanitarian work].

PMID- 21946578
TI  - [Stroke incidence and contradictions].

PMID- 21946579
TI  - [How to meet the unthinkable--Utoya 22 July 2011].

PMID- 21946580
TI  - Endure the pain of others.

PMID- 21946581
TI  - When worst comes to worst--the long road home.

PMID- 21946582
TI  - [Psychosocial interventions after a terrorist incident].

PMID- 21946583
TI  - Lean forward and be there.

PMID- 21946584
TI  - [When emergency services were put on test].

PMID- 21946585
TI  - [Utoya and Oslo].

PMID- 21946586
TI  - [Thank you to Norwegian physicians].

PMID- 21946587
TI  - Evidence-based  practice for Norwegian physicians?

PMID- 21946588
TI  - [COPD--not only in smokers].

PMID- 21946589
TI  - [Medical thermography--alternative diagnostics?].

PMID- 21946591
TI  - Can we trust  doping tests?

PMID- 21946592
TI  - [What's wrong with the difficult patient?].

PMID- 21946594
TI  - [Attitudes of medical students towards abortion].
AB  - BACKGROUND: It is not known whether the attitudes of Norwegian medical students
      towards abortion change in the course of their studies, or whether the attitudes
      differ among the four Norwegian medical schools. We have investigated attitudes
      towards abortion and the right to conscientious objection among medical students
      early and late in their studies at the four medical schools. Student satisfaction
      with the teaching on abortion was also surveyed. MATERIAL AND METHODS: A
      questionnaire survey was carried out among medical students at the four Norwegian
      medical schools, first year and fourth/fifth year students respectively. RESULTS:
      514 students (58.3 % of the students in the chosen classes) responded. 87.5 %
      approved of abortion on demand. The students at NTNU were the most liberal (93.5
      %). Fourth/fifth year students were more liberal than first year students (91.3 %
      vs. 84.7 %, p = 0.027). 27.3 % would want to exercise their right to
      conscientious objection. 41.5 % had been present at a surgical abortion. Of those
      who had not been present at a surgical abortion, 84.1 % would want to see an
      abortion being carried out if given the opportunity. 29 % agreed that the
      teaching did not adequately cover the ethical aspects of abortion.
      INTERPRETATION: Abortion on demand has wide approval among Norwegian medical
      students. However, many students would consider exercising their right to
      conscientious objection. More fourth/fifth year students than first year students
      approved of abortion.

PMID- 21946593
TI  - [Postoperative pain in patients admitted  to Norwegian hospitals].
AB  - BACKGROUND: Postoperative pain management is important for patients' well-being
      and mobility. It also reduces the length of hospital stays and prevents
      complications. Based on our own clinical experience, data on pain in cancer
      patients from Norway and on postoperative pain from other countries, we expected
      that a substantial proportion of patients staying in Norwegian hospitals would
      report postoperative pain of high intensity. MATERIAL AND METHODS: 215 in
      patients from 14 Norwegian hospitals participated in a study of pain during the
      first 24 hours after operations. The study was based on medical records and data
      reported by the patients themselves. RESULTS: On an 11-point numerical scale, the
      mean intensity of pain was 3.0 (SD 2.1) during the first 24 hours. 8 % of
      patients reported that the intensity of even the weakest pain during rest had
      been >= 4, 38 % reported a mean intensity >= 4 and 11 % reported a mean >= 6. The
      medical records contained information about the intensity of postoperative pain
      for only 22 % of the patients. Reports from patients indicated that 52 % had been
      asked to report the intensity of pain on a scale as part of the hospital routine,
      while 78 % and 74 % had been asked about the need for additional pain alleviation
      and whether the medication was effective. INTERPRETATION: Many patients reported
      pain of strong intensity during the first 24 hours after operations. There is a
      great potential for improved documentation and treatment of pain.

PMID- 21946595
TI  - [Post-operative pain management in hospitals].
AB  - BACKGROUND: Relief of post-operative pain has a bearing on the patient's well
      being, mobilisation and time confined to bed. The article discusses indications,
      contraindications and the efficacy of the various treatment modalities. MATERIAL
      AND METHOD: We have examined review articles, meta-analyses and randomised
      controlled trials, identified through literature searches in PubMed. RESULTS: The
      use of several medicines and techniques (multimodal pain treatment) is necessary
      to achieve a good balance between pain relief, side effects and risk. Systemic
      administration of paracetamol, NSAIDs, opioids and glucocorticoids is effective
      for post-operative pain. The same applies to epidural analgesia, peripheral nerve
      blocks and local anaesthetic wound infiltration. Subanaesthetic doses of ketamine
      have an opioid-sparing effect, but the optimal dosing regimen is uncertain.
      Gabapentinoids have an effect on post-operative pain, but the effect appears to
      vary depending on the type of operation and analgesic regimen. The effect of one
      analgesic will depend on which other drugs are used in multimodal pain treatment.
      Epidural analgesia, peripheral nerve blocks or extensive local infiltration
      analgesia is often necessary to relieve movement-related pain. INTERPRETATION:
      Many treatment modalities are effective for post-operative pain. It is crucial
      that the treatment is well organised and that it includes routines for systematic
      pain assessment, efficacy and side effects of the pain management.

PMID- 21946596
TI  - [Interactions between metoprolol and antidepressants].
AB  - BACKGROUND: Metoprolol, the most commonly used beta-receptor antagonist in
      Norway, is eliminated mainly via the enzyme cytochrome P450 (CYP) 2D6. This
      enzyme is inhibited to a varying extent by antidepressants. The aim of this
      article is to provide an overview of the interactions between metoprolol and
      antidepressants with an emphasis on CYP2D6 inhibition. MATERIAL AND METHODS:
      Relevant literature was identified by a PubMed search using the word "metoprolol"
      combined with generic names of antidepressant drugs. RESULTS: The potent CYP2D6
      inhibitor paroxetine has been shown to increase the biologically available dose
      of metoprolol about 4- to 6-fold. The same degree of increase is expected for the
      two other potent CYP2D6 inhibitors in the class, fluoxetine and bupropion. Severe
      bradycardia and atroventricular block has been reported in patients who have
      taken metoprolol in combination with these three drugs. Escitalopram, citalopram
      and duloxetine are less potent CYP2D6 inhibitors, and have been shown to cause 2-
      to 3-fold increases in biologically available dose of metoprolol. Other
      antidepressants, such as sertraline, venlafaxine, mianserin and mirtazapine,
      inhibit CYP2D6 to little or no extent, and are not expected to cause clinically
      relevant interactions with metoprolol. CONCLUSION: Metoprolol should not be used
      concomitantly with paroxetine, fluoxetine or bupropion due to extensive
      interactions and the risk of serious adverse effects. Dose reductions of
      metoprolol should be considered for combined treatment with citalopram,
      escitalopram or duloxetine, while concurrent use with sertraline, venlafaxine,
      mianserin and mirtazapine should be safe.

PMID- 21946597
TI  - [Vertebral osteomyelitis].

PMID- 21946598
TI  - Health as foreign policy.

PMID- 21946599
TI  - The idea of a convention for global health.

PMID- 21946600
TI  - Global health--from chaos to coherence.

PMID- 21946601
TI  - The World Health Organization and global health.

PMID- 21946602
TI  - International efforts for better health--Norway's role.

PMID- 21946603
TI  - [Fish and flatworms in Vietnam].

PMID- 21946608
TI  - Association of serum a disintegrin and metalloproteinase with thrombospodin motif
      4 levels with the presence and severity of coronary artery disease.
AB  - OBJECTIVE: A disintegrin and metalloproteinase with thrombospodin motif 4
      (ADAMTS4) has been shown to be an important player in atherosclerosis. However,
      the clinical significance of measuring serum ADAMTS4 levels has not been fully
      elucidated. We therefore investigate whether serum ADAMTS4 levels are associated
      with the presence and severity of coronary artery disease (CAD). METHODS: Serum
      levels of ADAMTS4 were measured in 192 patients undergoing elective coronary
      angiography for suspected CAD, the severity of CAD was determined by the number
      of diseased vessels and the severity score of coronary stenosis. RESULTS:
      Patients with CAD showed significantly higher levels of ADAMTS4 than did patients
      with normal coronary arteries [57.82 (48.96-70.32) vs. 46.55 (41.16-51.72) ng/ml,
      P<0.001]. ADAMTS4 levels increased with the number of diseased vessels (P<0.05)
      and significantly associated with severity score of stenosis (rs=0.601, P<0.001).
      In the multivariate analysis, ADAMTS4 levels were found to be independently
      correlated with the presence and severity of CAD. Receiver-operating
      characteristic analysis revealed that a cut-off of serum ADAMTS4 levels of 51.63
      ng/ml could predict CAD with a 76% sensitivity and a 69% specificity. ADAMTS4
      levels were significantly lower in patients with statin treatment than in those
      without it [47.49 (42.30, 57.09) vs. 56.39 (47.05, 68.94) ng/ml, P<0.05].
      CONCLUSION: In conclusion, serum ADAMTS4 levels are associated with the presence
      and the severity of CAD, ADAMTS4 might serve as an independent factor for
      predicting CAD. Statin therapy reduces the serum levels of ADAMTS4.

PMID- 21946609
TI  - Intraspinal cell transplantation for targeting cervical ventral horn in
      amyotrophic lateral sclerosis and traumatic spinal cord injury.
AB  - Respiratory compromise due to phrenic motor neuron loss is a debilitating
      consequence of a large proportion of human traumatic spinal cord injury (SCI)
      cases (1) and is the ultimate cause of death in patients with the motor neuron
      disorder, amyotrophic laterals sclerosis (ALS) (2). ALS is a devastating
      neurological disorder that is characterized by relatively rapid degeneration of
      upper and lower motor neurons. Patients ultimately succumb to the disease on
      average 2-5 years following diagnosis because of respiratory paralysis due to
      loss of phrenic motor neuron innnervation of the diaphragm (3). The vast majority
      of cases are sporadic, while 10% are of the familial form. Approximately twenty
      percent of familial cases are linked to various point mutations in the Cu/Zn
      superoxide dismutase 1 (SOD1) gene on chromosome 21 (4). Transgenic mice (4,5)
      and rats (6) carrying mutant human SOD1 genes ((G93A, G37R, G86R, G85R)) have
      been generated, and, despite the existence of other animal models of motor neuron
      loss, are currently the most highly used models of the disease. Spinal cord
      injury (SCI) is a heterogeneous set of conditions resulting from physical trauma
      to the spinal cord, with functional outcome varying according to the type,
      location and severity of the injury (7). Nevertheless, approximately half of
      human SCI cases affect cervical regions, resulting in debilitating respiratory
      dysfunction due to phrenic motor neuron loss and injury to descending bulbospinal
      respiratory axons (1). A number of animal models of SCI have been developed, with
      the most commonly used and clinically-relevant being the contusion (8).
      Transplantation of various classes of neural precursor cells (NPCs) is a
      promising therapeutic strategy for treatment of traumatic CNS injuries and
      neurodegeneration, including ALS and SCI, because of the ability to replace lost
      or dysfunctional CNS cell types, provide neuroprotection, and deliver gene
      factors of interest (9). Animal models of both ALS and SCI can model many
      clinically-relevant aspects of these diseases, including phrenic motor neuron
      loss and consequent respiratory compromise (10,11). In order to evaluate the
      efficacy of NPC-based strategies on respiratory function in these animal models
      of ALS and SCI, cellular interventions must be specifically directed to regions
      containing therapeutically relevant targets such as phrenic motor neurons. We
      provide a detailed protocol for multi-segmental, intraspinal transplantation of
      NPCs into the cervical spinal cord ventral gray matter of neurodegenerative
      models such as SOD1(G93A) mice and rats, as well as spinal cord injured rats and
      mice (11).

PMID- 21946610
TI  - Turning aluminium into a noble-metal-like catalyst for low-temperature activation
      of molecular hydrogen.
AB  - Activation of molecular hydrogen is the first step in producing many important
      industrial chemicals that have so far required expensive noble-metal catalysts
      and thermal activation. We demonstrate here that aluminium doped with very small
      amounts of titanium can activate molecular hydrogen at temperatures as low as 90
      K. Using an approach that uses CO as a probe molecule, we identify the atomistic
      arrangement of the catalytically active sites containing Ti on Al(111) surfaces,
      combining infrared reflection-absorption spectroscopy and first-principles
      modelling. CO molecules, selectively adsorbed on catalytically active sites, form
      a complex with activated hydrogen that is removed at remarkably low temperatures
      (115 K; possibly as a molecule). These results provide the first direct evidence
      that Ti-doped Al can carry out the essential first step of molecular hydrogen
      activation under nearly barrierless conditions, thereby challenging the monopoly
      of noble metals in hydrogen activation.

PMID- 21946611
TI  - A micromechanical model to predict the flow of soft particle glasses.
AB  - Soft particle glasses form a broad family of materials made of deformable
      particles, as diverse as microgels, emulsion droplets, star polymers, block
      copolymer micelles and proteins, which are jammed at volume fractions where they
      are in contact and interact via soft elastic repulsions. Despite a great variety
      of particle elasticity, soft glasses have many generic features in common. They
      behave like weak elastic solids at rest but flow very much like liquids above the
      yield stress. This unique feature is exploited to process high-performance
      coatings, solid inks, ceramic pastes, textured food and personal care products.
      Much of the understanding of these materials at volume fractions relevant in
      applications is empirical, and a theory connecting macroscopic flow behaviour to
      microstructure and particle properties remains a formidable challenge. Here we
      propose a micromechanical three-dimensional model that quantitatively predicts
      the nonlinear rheology of soft particle glasses. The shear stress and the normal
      stress differences depend on both the dynamic pair distribution function and the
      solvent-mediated EHD interactions among the deformed particles. The predictions,
      which have no adjustable parameters, are successfully validated with experiments
      on concentrated emulsions and polyelectrolyte microgel pastes, highlighting the
      universality of the flow properties of soft glasses. These results provide a
      framework for designing new soft additives with a desired rheological response.

PMID- 21946612
TI  - Differential stress induced by thiol adsorption on facetted nanocrystals.
AB  - Polycrystalline gold films coated with thiol-based self-assembled monolayers
      (SAM) form the basis of a wide range of nanomechanical sensor platforms. The
      detection of adsorbates with such devices relies on the transmission of
      mechanical forces, which is mediated by chemically derived stress at the organic
      inorganic interface. Here, we show that the structure of a single 300-nm-diameter
      facetted gold nanocrystal, measured with coherent X-ray diffraction, changes
      profoundly after the adsorption of one of the simplest SAM-forming organic
      molecules. On self-assembly of propane thiol, the crystal's flat facets contract
      radially inwards relative to its spherical regions. Finite-element modelling
      indicates that this geometry change requires large stresses that are comparable
      to those observed in cantilever measurements. The large magnitude and slow
      kinetics of the contraction can be explained by an intermixed gold-sulphur layer
      that has recently been identified crystallographically. Our results illustrate
      the importance of crystal edges and grain boundaries in interface chemistry and
      have broad implications for the application of thiol-based SAMs, ranging from
      nanomechanical sensors to coating technologies.

PMID- 21946613
TI  - Hierarchical self-assembly of suspended branched colloidal nanocrystals into
      superlattice structures.
AB  - Self-assembly of molecular units into complex and functional superstructures is
      ubiquitous in biology. The number of superstructures realized by self-assembly of
      man-made nanoscale units is also growing. However, assemblies of colloidal
      inorganic nanocrystals are still at an elementary level, not only because of the
      simplicity of the shape of the nanocrystal building blocks and their
      interactions, but also because of the poor control over these parameters in the
      fabrication of more elaborate nanocrystals. Here, we show how monodisperse
      colloidal octapod-shaped nanocrystals self-assemble, in a suitable solution
      environment, on two sequential levels. First, linear chains of interlocked
      octapods are formed, and subsequently the chains spontaneously self-assemble into
      three-dimensional superstructures. Remarkably, all the instructions for the
      hierarchical self-assembly are encoded in the octapod shape. The mechanical
      strength of these superstructures is improved by welding the constituent
      nanocrystals together.

PMID- 21946614
TI  - The use of technetium-99m hexamethylpropylene amine oxime lung scintigraphy in
      the detection of subclinical lung injury in patients with noninsulin-dependent
      diabetes mellitus.
AB  - PURPOSE: The aims of this study were to evaluate subclinical pulmonary injury in
      patients with noninsulin-dependent diabetes mellitus (NIDDM) who showed normal
      chest radiograph and pulmonary function test results by using technetium-99
      hexamethylpropylene amine oxime (Tc-99m-HMPAO) scintigraphy and to investigate
      the relationship between Tc-99m-HMPAO lung uptake and duration of diabetes,
      glycemic control, and the presence of diabetes-related microvascular
      complications. MATERIALS AND METHODS: A total of 40 patients with NIDDM (19 men,
      21 women; age 56.5 +/- 6.8 years; duration of diabetes: 13.1 +/- 6.7 years) were
      included in this study. The pulmonary vascular damage was represented as
      lung/liver uptake ratios (L/L ratios) calculated by Tc-99m-HMPAO lung
      scintigraphy. Results were compared with those of age-matched controls. RESULTS:
      The L/L ratio was 0.36 +/- 0.07 in normal controls and 0.51 +/- 0.16 in patients
      with NIDDM. The L/L ratio was significantly higher in NIDDM patients than in the
      control group (P=0.002). No correlation was observed between L/L ratio and the
      presence of diabetic complications, glycemic control, and diabetes duration.
      CONCLUSION: Tc-99m-HMPAO lung scintigraphy is a sensitive and an objective method
      for the detection of subclinical lung injury in NIDDM patients. Tc-99m-HMPAO lung
      uptake serves as an indicator of pulmonary injury due to diabetes, regardless of
      diabetes age, glycemic control, and the presence of other diabetes-related
      microvascular complications.

PMID- 21946615
TI  - Clinical significance of scintigraphic rapid gastric emptying.
AB  - OBJECTIVES: To analyse our results of gastric-emptying scintigraphy in relation
      to presenting symptoms, and examine in detail the clinical significance of rapid
      gastric emptying (RGE). MATERIALS AND METHODS: Results of 642 consecutive
      patients who underwent a solid gastric-emptying scintigraphy in our department
      over an 11-year period were retrospectively reviewed with particular emphasis to
      the presenting symptoms and the clinical profile of patients, especially of those
      who showed an accelerated pattern of emptying. RESULTS: Seventy (11%) patients
      were clinically suspected to have a RGE and 572 (89%) patients had presumed
      gastroparesis. Gastric emptying was found to be normal in 290 (45%), rapid in 182
      (28%) and delayed in 170 (27%) patients. Normal, rapid and delayed gastric
      emptying were seen, respectively, in 17 (24%), 48 (69%) and five (7%) patients
      with the clinical suspicion of dumping and 273 (48%), 134 (23%) and 165 (29%)
      patients with suspected gastroparesis. The positive predictive value of clinical
      suspicion for RGE was 62%, whereas the positive predictive value of delayed
      gastric emptying was 29%. Of the 182 patients with RGE, 144 (79%) were found to
      have no obvious explanation for this result; reactive hypoglycaemia was present
      in a quarter of these patients, but diarrhoea was seen only in 3%. CONCLUSION:
      Upper gastrointestinal symptoms have a poor clinical specificity to the actual
      rate of gastric emptying on scintigraphy. Diarrhoea as a symptom does not appear
      to be associated frequently with RGE, but our results confirm its relationship
      with hypoglycaemia. The majority of patients with a rapid emptying on gastric
      emptying scintigraphy have no identifiable cause for an accelerated motility.
      Scintigraphic gastric-emptying studies provide a reliable and noninvasive method
      of investigation in patients where conventional investigations have failed to
      establish the cause of upper gastrointestinal dysfunction.

PMID- 21946616
TI  - Association of vascular fluoride uptake with vascular calcification and coronary
      artery disease.
AB  - OBJECTIVE: The feasibility of a fluoride positron emission tomography/computed
      tomography (PET/CT) scan for imaging atherosclerosis has not been well
      documented. The purpose of this study was to assess fluoride uptake of vascular
      calcification in various major arteries, including coronary arteries. METHODS: We
      retrospectively reviewed the imaging data and cardiovascular history of 61
      patients who received whole-body sodium [18F]fluoride PET/CT studies at our
      institution from 2009 to 2010. Fluoride uptake and calcification in major
      arteries, including coronary arteries, were analyzed by both visual assessment
      and standardized uptake value measurement. RESULTS: Fluoride uptake in vascular
      walls was demonstrated in 361 sites of 54 (96%) patients, whereas calcification
      was observed in 317 sites of 49 (88%) patients. Significant correlation between
      fluoride uptake and calcification was observed in most of the arterial walls,
      except in those of the abdominal aorta. Fluoride uptake in coronary arteries was
      demonstrated in 28 (46%) patients and coronary calcifications were observed in 34
      (56%) patients. There was significant correlation between history of
      cardiovascular events and presence of fluoride uptake in coronary arteries. The
      coronary fluoride uptake value in patients with cardiovascular events was
      significantly higher than in patients without cardiovascular events. CONCLUSION:
      sodium [18F]fluoride PET/CT might be useful in the evaluation of the
      atherosclerotic process in major arteries, including coronary arteries. An
      increased fluoride uptake in coronary arteries may be associated with an
      increased cardiovascular risk.

PMID- 21946617
TI  - Impact of 18F-FDG PET/CT for detecting recurrence of medullary thyroid carcinoma.
AB  - OBJECTIVE: The aim of this study was to evaluate the value of fluorine-18 (18F)
      fluorodeoxyglucose (FDG) positron emission tomography/computed tomography
      (PET/CT) in the detection of recurrent medullary thyroid carcinoma (MTC) in
      patients with elevated calcitonin levels. METHODS: Thirty-three patients (nine
      men, 24 women; mean age: 50.3 +/- 12 years) who were referred to undergo 18F-FDG
      PET/CT for restaging of MTC in patients with high calcitonin levels were included
      in this study. Five patients also had suspected lymph nodes detected by neck
      ultrasonography. The results of 18F-FDG PET/CT and clinical follow-up data were
      reviewed retrospectively. Histological analysis has been accepted as the gold
      standard in the confirmation of 18F-FDG PET/CT results. Patients were followed up
      for 45.6 +/- 4.2 months. RESULTS: There were 14 negative and 19 positive scans
      for possible recurrence of MTC. In the positive scans, the possible recurrence
      sites were neck lymph nodes, thyroid bed, mediastinal lymph nodes, and the lung
      in 14, two, two, and one patient, respectively. Disease recurrence in 13 patients
      was confirmed histologically by surgical excision or fine-needle aspiration
      biopsy. In the remaining six patients, recurrence was excluded as it was reactive
      as a result of pathological examination. However, one patient had a negative
      scan, underwent neck lymph node excision after 18F-FDG PET/CT examination, and
      lymph node recurrence was detected histologically. According to these results,
      the sensitivity and specificity of PET/CT were calculated as 93 and 68%,
      respectively. According to the recommended calcitonin level by the American
      Thyroid Association (calcitonin levels higher than 150 pg/ml), sensitivity was
      calculated as 90%. Although the mean maximum standardized uptake values of the
      true-positive and false-positive groups were calculated as 4.72 +/- 2.17 and 4.22
      +/- 1.02, respectively, the difference between the two groups was not
      statistically significant (P>0.05). CONCLUSION: PET/CT is a sensitive imaging
      tool in the detection of MTC recurrence, especially in patients with high
      calcitonin levels, and it gives additional information in one third of all
      patients on an average by detecting an occult disease or confirming findings of
      other imaging tools.

PMID- 21946618
TI  - Building PET research collaborations.
AB  - Collaborations help to stimulate scientific research by sharing of expertise,
      knowledge, equipment, and research products. Cooperation benefits multicentre
      positron emission tomography (PET) trials by speeding up recruitment, allowing
      larger studies to be performed and making it feasible to recruit sufficient
      patients to study atypical tumour types. Mechanisms are being developed to
      encourage UK PET centres to collaborate with other UK centres, industrial
      partners, and PET centres in other countries. This editorial explores these
      different types of collaboration, highlighting interesting opportunities,
      potential issues that may be encountered, and three areas where the NCRI PET
      Research Network are trying to promote group effort.

PMID- 21946619
TI  - A method of generating image-derived input function in a quantitative 18F-FDG PET
      study based on the shape of the input function curve.
AB  - PURPOSE: A method for defining image-derived input function (IDIF) has been
      introduced and evaluated for the quantification of the regional cerebral
      metabolic rate of glucose in positron emission tomography studies. MATERIALS AND
      METHODS: First, a cubic region of interest containing the carotid artery was
      defined. The useful voxels in this cubic region, whose time-activity curves
      (TACs) decrease as assessed by linear regression after the initial rapid rise
      (about 2 min after injection), were selected, and their TACs were averaged to
      obtain the raw TAC of the IDIF. The IDIF was obtained from the raw TAC after
      correcting for partial volume and spillover effects using two blood samples. Data
      from 16 human subjects were used to test the proposed method. The Patlak approach
      was used to calculate the net 18F-fluoro-2-deoxyglucose (FDG) clearance with
      plasma-derived input function and our generated IDIF. RESULTS: The net FDG
      clearances calculated with the image-derived input function generated by our
      approach are consistent with those calculated with plasma-derived input function.
      The relative error percentages of the net FDG clearances calculated with the
      image-derived input function and the plasma derived input function are about 5%.
      CONCLUSION: This study proposed a method to obtain the input function from the
      dynamic positron emission tomography images. The method was accurate and
      convenient to use.

PMID- 21946620
TI  - A new method for the radiochemical purity measurement of 111In-pentetreotide.
AB  - OBJECTIVES AND METHODS: The recommended method for the measurement of
      radiochemical purity (RCP) of 111In-labelled pentetreotide is thin-layer
      chromatography with a silica gel as the stationary phase and a 0.1 N sodium
      citrate solution (pH 5) as the mobile phase. According to the supplier's
      instructions, the mobile phase must be prepared before the test is carried out,
      and the recommended stationary phase is off-market. We propose a new method for
      RCP measurement in which the mobile phase is acid citrate dextrose, solution A,
      which does not need to be prepared beforehand, and thin-layer chromatography is
      performed with a silica gel-impregnated glass fibre sheet as the stationary
      phase. We used both methods to measure the percentages of radiopharmaceutical and
      impurities. RESULTS: The range of RCP values obtained was 98.0-99.9% (mean=99.3%)
      by the standard method and 98.1-99.9% (mean=99.2%) by the new method. We observed
      no differences between the RCP values of both methods (P=0.070). CONCLUSION: The
      proposed method is suitable for RCP testing because it yields results that are in
      good agreement with those of the standard method and because it is easier to
      perform as the mobile-phase solution need not be prepared in advance.

PMID- 21946621
TI  - Unlocking the secrets of immunoglobulin receptors in mantle cell lymphoma:
      implications for the origin and selection of the malignant cells.
AB  - Immunogenetic analysis of mantle cell lymphoma (MCL) has offered important
      evidence helping to decipher the immune pathways leading to its development and
      also prompting a reappraisal of the views about its ontogeny. In particular,
      older and more recent studies have demonstrated that MCL is characterized by a
      highly distinctive immunoglobulin gene repertoire with remarkable predominance of
      the IGHV3-21 and IGHV4-34 genes; restricted associations of IGHV, IGHD and IGHJ
      genes, culminating in the creation of quasi-identical ("stereotyped") heavy
      complementarity-determining region 3 sequences in roughly 10% of cases; and, very
      precisely targeted and, probably, functionally driven somatic hypermutation,
      ranging from minimal (in most cases) to pronounced. Furthermore, comparison to
      other entities, in particular CLL, revealed that several of these immunogenetic
      features are "MCL-biased". On these grounds, an antigen-driven origin of MCL
      could be envisaged, at least for subsets of cases.

PMID- 21946622
TI  - Epigenetic alterations associated with cellular senescence: a barrier against
      tumorigenesis or a red carpet for cancer?
AB  - Cellular senescence is eminently characterized by a permanent cell cycle arrest
      and the acquisition of morphological, physiological and epigenetic changes. The
      establishment of cellular senescence can occur in response to telomere attrition
      associated with cell turnover and ageing or following oncogene activation.
      Although seemingly two distinct phenomena, cellular senescence and cancer share
      similarly altered global epigenetic profiles comprising changes in DNA
      methylation, involving global hypomethylation of repetitive DNA sequences and
      regional hypermethylation of some gene promoters, and in histone post
      translational modifications. As epigenetic and genetic alterations are likely to
      act synergistically in cancer, anomalous epigenetic marks acquired during ageing
      or in response to oncogene activation might play important roles in tumorigenesis
      and cancer progression. These potentially tumor-promoting epigenetic alterations
      include transcriptional repression of genes encoding tumor suppressors or
      developmentally regulated proteins, expression of non-coding repetitive RNAs and
      acquisition of distinct heterochromatin marks that may contribute to suppress
      cell death by reducing DNA damage response. Cellular senescence may thus be
      viewed as a double-edged sword that, although acting as a potent anti
      proliferative barrier, may pave the way to tumorigenesis in senescence-escaping
      cells by altering their epigenetic make up.

PMID- 21946625
TI  - Reliability and validity of the International Physical Activity Questionnaire
      (IPAQ) in elderly adults: the Fujiwara-kyo Study.
AB  - BACKGROUND: The International Physical Activity Questionnaire (IPAQ) is a self
      reported questionnaire for assessing physical activity and has been tested in 12
      countries among adults aged 18 to 65 years. The present study evaluated the
      reliability and validity of the IPAQ among adults aged 65 years and older.
      METHODS: The study included 164 men and 161 women selected from participants of
      the Fujiwara-kyo Study, a prospective cohort of elderly Japanese adults. To
      examine test-retest reliability, the participants were asked to complete the IPAQ
      twice, 2 weeks apart. The criterion validity of the IPAQ was tested by using an
      accelerometer. RESULTS: Based on intraclass correlation coefficients, the
      reliability of the total IPAQ was 0.65 and 0.57 for men and women, respectively,
      aged 65 to 74 years and 0.50 and 0.56 for those aged 75 to 89 years. The Spearman
      correlation coefficients between total IPAQ score and total physical activity
      measured by accelerometer (TPA-AC) were 0.42 and 0.49 for men and women,
      respectively, aged 65 to 74 and 0.53 and 0.49 for those aged 75 to 89. Weighted
      kappa coefficients between total IPAQ score and TPA-AC were 0.49 and 0.39 for men
      and women, respectively, aged 65 to 74 and 0.46 and 0.47 for those aged 75 to 89.
      CONCLUSIONS: The reliability of the IPAQ was not sufficient, but the validity was
      adequate. Although there were some limitations with regard to repeatability and
      agreement in classification, the IPAQ was a useful tool for assessing physical
      activity among elderly adults.

PMID- 21946623
TI  - Repairing split ends: SIRT6, mono-ADP ribosylation and DNA repair.
AB  - The sirtuin gene family comprises an evolutionarily ancient set of NAD+ dependent
      protein deacetylase and mono-ADP ribosyltransferase enzymes. Found in all domains
      of life, sirtuins regulate a diverse array of biological processes, including DNA
      repair, gene silencing, apoptosis and metabolism. Studies in multiple model
      organisms have indicated that sirtuins may also function to extend lifespan and
      attenuate age-related pathologies. To date, most of these studies have focused on
      the deacetylase activity of sirtuins, and relatively little is known about the
      other biochemical activity of sirtuins, mono-ADP ribosylation. We recently
      reported that the mammalian sirtuin, SIRT6, mono-ADP ribosylates PARP1 to promote
      DNA repair in response to oxidative stress. In this research perspective we
      review the role of SIRT6 in DNA repair and discuss the emerging implications for
      sirtuin directed mono-ADP ribosylation in aging and age-related diseases.

PMID- 21946626
TI  - Change in causes of injury-related deaths in South Korea, 1996-2006.
AB  - BACKGROUND: The aims of this study were to describe temporal patterns of injury
      related mortality by sex, age group, and mechanism, and to identify changes in
      the leading causes of injury-related deaths in South Korea from 1996 through
      2006. METHODS: This retrospective, descriptive study analyzed national data on
      all injury-related deaths reported in official death certificates from 1996-2006.
      Incidence rates of fatal injuries are presented as crude and age-standardized
      rates per 100 000 population, and percentage changes in injury-related
      mortalities over the 11-year period were calculated with respect to intention,
      sex, and age. The 4 most common mechanisms (fall, poisoning, suffocation, and
      drowning) were then classified as unintentional injuries or suicides. RESULTS:
      Overall injury-related mortality decreased 31.7% during the study period (1996
      2006). Despite this overall decreasing trend, injury-related mortality increased
      among adults aged 65 years or older. In particular, injury-related mortality
      among women older than 80 years doubled since 1996. Suicide replaced transport as
      the leading cause of injury-related deaths between 2003 and 2006. With regard to
      intention, sex, and age, the most noticeable changes during the study period were
      increases in unintentional fall among elderly adults and suicidal fall among
      adolescents. CONCLUSIONS: The incidence rate for all injuries generally decreased
      from 1996-2006. However, the incidence rate of fall injuries increased among
      elderly adults, and suicide increased among adolescents. These findings suggest
      that further investigation of the characteristics and trends of injuries is
      necessary to develop and implement effective interventions.

PMID- 21946627
TI  - Prehypertension and clustering of cardiovascular risk factors among adults in
      suburban Beijing, China.
AB  - BACKGROUND: Prehypertension is common in China and is associated with an
      increased risk of cardiovascular disease. The present study estimated the current
      prevalence of prehypertension and its association with clustering of other
      modifiable cardiovascular risk factors (CRFs) among adults in suburban Beijing.
      METHODS: A cross-sectional survey of a representative sample of 19 003 suburban
      adults aged 18 to 76 years was carried out in 2007. Questionnaire data and
      information on blood pressure, anthropometric characteristics, and laboratory
      measurements were collected. RESULTS: The age-standardized prevalence of
      prehypertension was 35.7% (38.2% in men and 31.8% in women) among adults in
      suburban Beijing. The prevalence of overweight/obesity, diabetes, dyslipidemia,
      and physical inactivity was higher in participants with prehypertension (26.7%,
      4.8%, 34.3%, and 60.4%, respectively) as compared with normotensive participants
      (15.9%, 2.7%, 20.5%, and 29.1%, respectively), and in participants with
      hypertension as compared with those with prehypertension. Overall, 85.3%, 49.8%,
      and 17.8% of prehypertensive men had 1 or more, 2 or more, and 3 or more CRFs
      (overweight/obesity, diabetes, dyslipidemia, current smoking, and physical
      inactivity). These proportions were higher than those in normotensive men (81.5%,
      45.1%, and 13.4%) and lower than those in men with hypertension (91.7%, 56.4%,
      19.2%). Similar results were found when women with prehypertension were compared
      with women who were normotensive or hypertensive. CONCLUSIONS: A high prevalence
      of prehypertension and clustering of other modifiable CRFs are common among
      prehypertensive adults in suburban Beijing. More-effective population-based
      lifestyle modifications are required to prevent progression to hypertension and
      reduce the increasing burden of cardiovascular disease in China.

PMID- 21946629
TI  - Health inequities are rising unseen in New Zealand.

PMID- 21946630
TI  - The challenge of reducing socioeconomic and ethnic differences in cardiovascular
      disease.

PMID- 21946631
TI  - Leveraging information from New Zealand statistical data: a first step to wisdom
      in transforming unmet need for general practice services.

PMID- 21946632
TI  - Reducing a striking health inequality.

PMID- 21946633
TI  - Sociodemographic differences in prevalence of diagnosed coronary heart disease in
      New Zealand estimated from linked national health records.
AB  - AIM: To estimate sociodemographic differences in the prevalence of coronary heart
      disease (CHD) in New Zealand from linked health records. METHODS: We combined
      records of hospital treatment for CHD, dispensing of selected anti-anginal drugs
      and mortality to estimate the national point prevalence of coronary heart disease
      in New Zealand in December 2008. Stratified estimates are presented by gender;
      age; Maori, Pacific, Indian and 'Other' (mainly New Zealand European) ethnic
      groups; and socioeconomic status. RESULTS: Among a "health contact" population of
      adults (greater than and equal to 15 years), about one in twenty (6.5% of men and
      4.1% of women) had indicators of a past diagnosis or treatment for CHD or both.
      Substantial differences in prevalence occurred by gender, ethnic group and
      socioeconomic status. For example, among New Zealanders aged 35 to 74 years,
      Indian men had the highest age-adjusted prevalence (7.78%; 95%CI 7.43 to 8.15),
      almost double the prevalence of 'Other' males. Among women, Maori had the highest
      adjusted prevalence (4.03%; 95% CI 3.89 to 4.17), just over twice that of
      'Others.' CONCLUSION: Major sociodemographic disparities in the national burden
      of CHD persist. Our results are similar to previous studies of ethnic disparities
      in CHD incidence, but also confirm concerns about the emerging CHD burden among
      South Asians. Indian males have the highest CHD prevalence of any gender-specific
      ethnic group. Of equal concern, Maori women have a similar prevalence to European
      males.

PMID- 21946634
TI  - Unmet need of GP services in Pacific people and other New Zealanders.
AB  - AIM: To compare the unmet need of GP services for Pacific peoples (mostly of
      Samoan, Tongan, Niuean, or Cook Islands origin) and Other New Zealanders
      (predominantly European New Zealanders, Maori, and Asian New Zealanders).
      METHODS: The New Zealand Health Survey 2006/2007 sampled 12,488 people, aged 15+
      years, living in private dwellings in New Zealand. Of these 1033 were Pacific
      peoples and 11,455 were Other New Zealanders. Self-reported unmet GP need in the
      previous 12 months was modelled using logistic regression with sociodemographic,
      health status and risk variables as covariates. RESULTS: Age, sex, educational
      level, New Zealand individual Deprivation Index, self-rated health, spinal
      disorders and daily smoking were associated with unmet GP need. Ethnicity has two
      interactions in the model, one with asthma and the other with body mass index
      (BMI). The difference in unmet need between Pacific peoples and Other New
      Zealanders was explained in part by Pacific peoples being more likely to be in
      categories with more deprivation characteristics but countered by Other New
      Zealanders having a higher probability of having higher educational
      qualifications where there was also higher unmet need. Those with unmet GP need
      in the higher educational levels were more likely to say "they couldn't spare the
      time". CONCLUSION: Unmet GP need is associated with ethnicity, health need and
      financial and time constraints.

PMID- 21946635
TI  - Throat swabbing for the primary prevention of rheumatic fever following health
      information.
AB  - AIM: To determine whether health promotion activities in March-August 2009
      increased sore throat swabbing rates among Flaxmere (Hawke's Bay, New Zealand)
      children aged 5-14 years, and in particular among Maori and Pacific children.
      METHOD: Monthly totals of Hawke's Bay bacterial throat swabs for the period March
      October 2008 and March-October 2009 were obtained. Using Poisson regression, the
      2008 and 2009 test rates for Flaxmere children residing in the target area during
      the intervention were compared with non-Flaxmere children. Flaxmere test rates
      were determined for Maori or Pacific children and non-Maori non-Pacific children
      separately. RESULTS: Flaxmere children had a higher pre-intervention bacterial
      throat swab rate, compared to non-Flaxmere children (6.0% vs 3.2%; p<0.001). The
      throat swab rate increased significantly for Flaxmere children during the
      intervention period, compared to both the previous year (1.6; 1.3-2.0) and
      compared to the increase observed among non-Flaxmere children (1.4; 1.1-1.8).
      Subanalysis among Flaxmere children found a significant increase in the throat
      swab rate of Maori and Pacific children (1.8; 1.4-2.4). CONCLUSIONS: A
      demonstrable increase in throat swabbing rates among high-risk Flaxmere children
      was observed following a combination of health promotion interventions. The
      increase in throat swabbing rates observed among Maori and Pacific children
      suggest that the intervention was effective for children with the highest risk.

PMID- 21946636
TI  - Achieving equitable outcomes for Maori women with cervical cancer in New Zealand:
      health provider views.
AB  - AIM: This study explored health provider views on changing survival disparities
      between Maori and non-Maori women, the management of cervical cancer in New
      Zealand, and achieving equitable outcomes from cervical cancer for Maori women.
      METHODS: This research followed on from a cohort study of cervical cancer
      treatment and survival in New Zealand. Focus groups were undertaken with three
      provider groups in different regions working across the range of cervical cancer
      services. Focus group transcripts were analysed to identify key themes. RESULTS:
      Providers were encouraged by the reported improvement in survival disparities
      between Maori and non-Maori women over time. The themes of discussion relating to
      cervical cancer management included: communication and education; screening;
      access to treatment; pathways through care; patient factors; and, system
      standards. Providers also suggested options for further improvements in the
      management of cervical cancer. CONCLUSIONS: The focus groups identified that
      despite improvements over time in cervical cancer disparities between Maori and
      non-Maori and in the management of cervical cancer, further effort is required to
      achieve equitable outcomes for Maori, particularly in the areas of prevention and
      early detection.

PMID- 21946637
TI  - Students' and teachers' perceptions of the clinical learning environment in years
      4 and 5 at the University of Auckland.
AB  - AIM: As the undergraduate medical curriculum is developed in response to an
      increasing number of students across multiple teaching sites, it is timely to
      review the clinical learning environment of medical students in the first two
      clinical years. METHOD: University of Auckland students in year 4 and 5 completed
      the Dundee Ready Educational Environment Measure (DREEM). Clinical Teachers
      completed a shorter questionnaire on their perceptions of the clinical learning
      environment. RESULTS: The students perceive their clinical learning environment
      positively and their perceptions compare favourably with similar studies
      internationally. The DREEM is reliable for and practical to use in the New
      Zealand undergraduate clinical learning environment. Learning site, year of
      study, clinical team, gender, age, or ethnicity did not influence students'
      perceptions of their learning environment. Clinical teachers view their teaching
      positively but there seem to be concerns over the amount of time they have
      available for teaching. CONCLUSION: Students are concerned about the amount of
      knowledge they need to acquire and the availability of support for students under
      stress as they enter and during the clinical years. Clinical teachers are
      concerned about the amount of time they have available for teaching.

PMID- 21946638
TI  - Leave provision for Canterbury District Health Board's resident medical officers
      with sick leave analyses.
AB  - This study reports an analysis of the leave taken, over a 12-month period by
      Canterbury District Health Board Registrars and House Officers.

PMID- 21946639
TI  - What risk do consumers face when seeking medical advice from health food stores?
AB  - AIM: There is currently no specific legislation to regulate either complementary
      and alternative medicine (CAM) products or the majority of those promoting them.
      This study sought to highlight the general risk a consumer may face when they
      seek help/advice from a pharmacy or health food store (HFS). METHODS: 21 HFS,
      matched with pharmacies, were visited by a researcher complaining of tiredness,
      who stated he had been taking warfarin over the previous 2 months. The name,
      manufacturer and retail price of any products recommended were recorded
      immediately after leaving the premises. Paired contingency table analysis was
      used. RESULTS: A pharmacy was significantly more likely to advise the consumer to
      consult a doctor (13/21) than a HFS (3/21) with a difference in marginal
      proportions of 47.6% (95% CI 22.5-72.7), p=0.006. A HFS was more likely to
      recommend more products, and only about one-quarter gave appropriate advice
      regarding possible interactions with warfarin and management of anticoagulation
      compared with two-thirds of pharmacies. CONCLUSION: To provide safe and quality
      advice to consumers, those promoting CAM products need to obtain relevant history
      and give accurate information regarding possible dug interactions and be prepared
      to refer back to mainstream medical services. Better regulation of CAM products
      and those promoting them is called for.

PMID- 21946640
TI  - Mind the Gap: ethical issues of private treatment in the public health system.
AB  - The funding of expensive new cancer treatments is a difficult health policy issue
      in New Zealand and around the world. Since the public health system cannot afford
      to fund every new treatment, complex decisions must be made about which
      treatments to fund publicly, and whether and how to make unfunded treatments
      available to people who may wish to fund them themselves. One recent proposal is
      that unfunded treatments be made available to patients privately through the
      local public hospital. Although ultimately declined by the health minister, this
      proposal merits serious debate, since it is likely to continue to attract
      attention as a policy option. While the integration of public and private
      delivery systems has clear benefits for patients with the means to purchase
      additional treatments, its overall effect may be to exacerbate existing
      inequities in the New Zealand health sector. This paper briefly explores the
      wider ramifications of such schemes as part of the ongoing public discussion that
      should inform the development of health policy on this issue.

PMID- 21946641
TI  - Managing obstructive sleep apnoea and achieving equity: implications for health
      services.
AB  - Sleep occupies a third of life, and poor sleep has wide-ranging consequences for
      health, safety, and well-being. Recent research suggests significant inequalities
      in sleep health between Maori and non-Maori adults in New Zealand including self
      reported sleeping problems and obstructive sleep apnoea syndrome (OSAS). This
      paper will outline a series of studies that were designed to assess how many
      people were affected by OSAS in Aotearoa/New Zealand and specifically sought to
      prioritise the needs of Maori. It will discuss a number of issues related to the
      diagnosis and treatment of OSAS in New Zealand and present strategies for
      reducing inequalities in sleep health.

PMID- 21946642
TI  - Medical image. A left atrial myxoma presenting as angina.

PMID- 21946643
TI  - Medical image. Pathognomonic rash.

PMID- 21946644
TI  - Does health evidence support or undermine our regulatory approach to air quality?

PMID- 21946645
TI  - Hand hygiene practices at a hospital entrance after the 2009 influenza pandemic:
      observational study over one year.

PMID- 21946646
TI  - Against anterior cruciate ligament reconstructions--and response by orthopaedic
      surgeon.

PMID- 21946647
TI  - Why so many stillbirths?

PMID- 21946648
TI  - Response to letter from Prof Shaun Holt calling for doctors not to practice
      homeopathy.

PMID- 21946649
TI  - Melanoma Summit highlights best practice and priorities for action.

PMID- 21946650
TI  - Contribution of hepatitis B vaccination programmes initiated by Alexander Milne
      and Dr Christopher Moyes to the decline in prevalence of hepatitis B infection in
      pregnant women in the Midlands region of the North Is, New Zealand.

PMID- 21946651
TI  - The limited role of MRI in long-term follow-up of patients with Takayasu's
      arteritis.
AB  - INTRODUCTION: MRI and MRA are used for diagnosis and activity determination of
      patients with Takayasu's arteritis (TA). However, there is a limited experience
      regarding the role of MRI in long-term follow-up of those patients. The aim of
      the present study was to evaluate the clinical usefulness of MRI in the long-term
      follow-up of patients with Takayasu's disease. MATERIALS AND METHODS: The
      clinical data of 11 TA patients, who obtained two or more follow-up MRI scans,
      was matched with the imaging results. MRI examinations were considered positive
      for disease activity when one of the following findings was noted: new arterial
      wall enhancement or interval appearance of anatomical changes (interval
      dilatation, stenosis or occlusion or new arterial wall irregularity). Conversely,
      MRI examinations were considered to show signs of improvement when local
      enhancement disappeared, or when a stenosis was relieved. Disease activity was
      determined by the combination of worsening localizing ischemic signs and
      symptoms, systemic signs and symptoms (malaise, fever, etc.), and elevated blood
      markers (CRP and ESR). RESULTS: A total of 47 MRI examinations were performed in
      11 patients (1 male, mean age 28, range 14-53 years) with a total follow-up time
      ranging between 12 and 56 months (average 36 months). MRI was positive for active
      disease at least once in nine out of the 11 patients (82%). The most commonly
      affected arteries were the aortic arch, the left subclavian artery and the left
      common carotid artery. No statistically significant correlation was found between
      clinical activity and MRI signs of activity. CONCLUSION: Although MRI is a well
      established modality for primary diagnosis of TA, the present study suggests that
      it has a limited clinical role in the long-term follow-up of those patients when
      reactivation of disease is suspected.

PMID- 21946652
TI  - In situ synthesis of gold nanoparticles on porous polyacrylonitrile nanofibers
      for sensing applications.
AB  - A simple and cost-effective method was reported to synthesize small size (6 nm)
      gold nanoparticles (AuNPs) on polyacrylonitrile (PAN) electrospun nanofibers
      (AuNPs/PAN). The formation of AuNPs is attributed to the in situ reduction of
      Au(III) to Au(0) by 4-(dimethylamino)benzaldehyde doped in the PAN nanofibers.
      Electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV)
      confirmed that the AuNPs/PAN nanofibers showed good conductivity. The AuNPs/PAN
      nanofibers were used to immobilize tris(2,2'-bipyridyl)ruthenium(II) ions
      (Ru(bpy)(3)(2+)) to form an electrochemiluminescence (ECL) sensor. The AuNPs on
      the PAN nanofibers exhibited an excellent catalytic effect on the ECL of
      Ru(bpy)(3)(2+) which could be employed to detect low concentrations of phenolic
      compounds. The linear response range of the ECL sensor to hydroquinone is 0.55-37
      MUM with limit of detection of 80 nM (S/N = 3). This sensor has been successfully
      applied to determine the hydroquinone content in photographic developer samples.
      Our work provides a very simple and cost-effective method to synthesize AuNPs on
      polymer nanofibers which shows great potential in the field of electrocatalysis
      and chemo/biosensors.

PMID- 21946653
TI  - Survey of the current status of teaching intensive care medicine in Australia and
      New Zealand medical schools.
AB  - INTRODUCTION: The place of Intensive Care Medicine education within Medical
      Schools in Australia and New Zealand was investigated by survey in 2009.
      MATERIALS AND METHODS: All intensive care units in Australia and New Zealand were
      invited to take part in the survey. The survey included commitment to intensive
      care medicine training, teaching methods, curriculum content, assessment, and
      hours of student contact. All university teaching hospitals were identified and
      results analyzed. INTERVENTIONS: None. RESULTS: From recognized tertiary referral
      teaching hospitals, the response was 60%. A mandatory teaching program was
      offered by 56%, with a further 22% offering an optional program. The medical
      school curricula were primarily a mix of problem-based learning and traditional,
      lecture-based courses. Intensive care experience was usually undertaken in the
      latter years of the course. Contact hours allocated under the curriculum was less
      than 1 wk in the great majority. Assessment of students, where it existed, was
      undemanding. Intensive care medicine, although growing in stature within medical
      schools, still appears to occupy only a small place in the overall curriculum.
      CONCLUSION: A survey was undertaken to determine the extent of intensive care
      medicine training undertaken in medical student courses in Australia and New
      Zealand. A small majority of university hospitals had mandatory programs, with
      nearly a quarter having neither a mandatory or optional program. This is a higher
      proportion than identified in previous international surveys, but the results
      indicate considerable deficits requiring ongoing development within the
      undergraduate program.

PMID- 21946654
TI  - Cooling the crisis: therapeutic hypothermia after sickle cardiac arrest.
AB  - OBJECTIVE: The management of patients with sickle-cell disease and cardiac arrest
      presents special challenges. Mild therapeutic hypothermia may improve survival
      and neurologic outcome after cardiac arrest, however, it may also precipitate
      sickling in patients with sickle-cell disease. Rigorous exchange transfusion may
      enable mild therapeutic hypothermia after cardiac arrest in patients with sickle
      cell disease. DESIGN: Case report. SETTING: A 28-bed closed format intensive care
      unit in a university hospital. PATIENT: A 41-yr-old man with a double
      heterozygous sickle-cell beta-0 thalassemia was admitted to the internal ward for
      acute chest syndrome. On the third day he developed cardiac arrest. Return of
      spontaneous circulation was achieved after 45 mins of full cardiopulmonary
      resuscitation. INTERVENTIONS: Postcardiac arrest rigorous exchange transfusion
      and mild therapeutic hypothermia were applied. MEASUREMENT AND MAIN RESULT:
      Erythrocytapheresis lowered the content of hemoglobin S to 5.6%, and therapeutic
      hypothermia was successfully maintained for 24 hrs without adverse events. After
      2 critical weeks, the patient regained full consciousness. CONCLUSION:
      Therapeutic hypothermia after cardiac arrest is feasible following rigorous
      exchange transfusion in patients with sickle-cell disease.

PMID- 21946655
TI  - Acute lung injury in critical neurological illness.
AB  - OBJECTIVE: Acute lung injury and acute respiratory distress syndrome have been
      reported in a significant proportion of patients with critical neurologic
      illness. Our aim was to identify risk factors for acute lung injury/acute
      respiratory distress syndrome in this population. DESIGN: Prospective,
      observational study. SETTING: A 22-bed, adult neurosciences critical care unit at
      a tertiary care hospital. PATIENTS: Primary neurologic disorder, mechanical
      ventilation >48 hrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total
      of 192 patients were enrolled with a range of neurologic disorders. Among these,
      68 (35%) were diagnosed with acute lung injury/acute respiratory distress
      syndrome. In a multivariate logistic regression analysis, independent risk
      factors for acute lung injury/acute respiratory distress syndrome were pneumonia
      (odds ratio [95% confidence interval] 3.12 [1.5-6.0], p = .002), circulatory
      shock (2.2 [1.07-4.57], p = .03), and absence of a gag or cough reflex (3.41
      [1.34-8.68], p = .01). Neither neurologic diagnosis nor neurologic severity,
      assessed with the Glasgow Coma Scale, was significantly associated with the
      development of acute lung injury/acute respiratory distress syndrome. CONCLUSION:
      Acute lung injury/acute respiratory distress syndrome occurred in more than one
      third of mechanically ventilated neurosciences critical care unit patients. Loss
      of the cough or gag reflex is strongly predictive of acute lung injury/acute
      respiratory distress syndrome, while neurologic diagnosis and Glasgow Coma Scale
      are not. Lower brainstem dysfunction, a clinical marker of neurologic injury not
      captured by the Glasgow Coma Scale, is a risk factor for acute lung injury/acute
      respiratory distress syndrome and could inform decisions regarding airway
      protection and mechanical ventilation.

PMID- 21946656
TI  - Determinants of renal potassium excretion in critically ill patients: the role of
      insulin therapy.
AB  - OBJECTIVES: Insulin administration lowers plasma potassium concentration by
      augmenting intracellular uptake of potassium. The effect of insulin
      administration on renal potassium excretion is unclear. Some studies suggest that
      insulin has an antikaliuretic effect although plasma potassium levels were poorly
      controlled. Since the introduction of glycemic control in the intensive care
      unit, insulin use has increased. We examined the relation between administered
      insulin and renal potassium excretion in critically ill patients under computer
      assisted glucose and potassium regulation. DESIGN: Prospective observational
      study. SETTING: Twelve-bed surgical intensive care unit of a university teaching
      hospital. PATIENTS: Consecutive intensive care unit patients. INTERVENTIONS:
      Potassium and glucose levels were regulated by a computer-assisted decision
      support system. Both potassium and insulin were continuously administered by
      syringe pump. MEASUREMENTS AND MAIN RESULTS: Renal potassium excretion was
      measured daily in the 24-hr urine collections. The 24-hr urinary samples of
      patients with kidney failure or on renal replacement therapy were excluded.
      Multivariate analysis with potassium excretion as the dependent variable was
      performed. In 178 consecutive patients, 1,456 24-hr urinary samples, were
      analyzed. Mean +/- SD plasma potassium was 4.2 +/- 0.3 mmol/L, with 79 +/- 46
      mmol/d of potassium administered and a mean insulin dose of 53 +/- 38 U/day.
      Renal potassium excretion was 126 +/- 51 mmol/day. After multivariate analysis
      correcting for relevant variables (including diuretics, pH, potassium levels and
      renal sodium excretion), insulin administration was independently and positively
      associated with renal potassium excretion. Other significant variables were
      potassium levels, potassium administration, renal sodium and chloride excretion,
      creatinine clearance, diuretic therapy, pH, known diabetes and intensive care
      unit admission day (R = .52; p <. 001). CONCLUSION: Insulin administration is
      associated with an increase in the renal potassium excretion in critically ill
      patients.

PMID- 21946657
TI  - Hypercapnic acidosis attenuates reperfusion injury in isolated and perfused rat
      lungs.
AB  - OBJECTIVE: Although ischemia-reperfusion injury is a major determinant of primary
      graft dysfunction after lung transplantation, an approach to extend preoperative
      lung preservation to postoperative protection has not yet been defined. The
      purpose of this study was to determine the protective effects of and the signal
      pathway regulated by hypercapnic acidosis in ischemia-reperfusion-induced lung
      injury. DESIGN: Animal study. SETTING: Animal care facility procedure room in a
      medical center. SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: Lung
      injury was induced in a clinically relevant ex vivo animal model. Animals were
      divided into a control group (FICO(2), 5%; n = 6), ischemia-reperfusion group
      (FICO(2), 5%; n = 6), and hypercapnic acidosis (ischemia-reperfusion +
      hypercapnic acidosis) group (FICO(2), 10%; n = 6). MEASUREMENTS AND MAIN RESULTS:
      Ischemia-reperfusion caused significant increases in alveolar lavage and
      perfusate tumor necrosis factor-alpha, inflammatory cell infiltration, lung
      tissue malondialdehyde, bronchoalveolar lavage fluid protein concentration and
      lactate dehydrogenase activity, lung weight gain, and infiltration coefficient.
      Ventilation with 10% CO(2) significantly suppressed the inflammatory response and
      attenuated lung ischemia-reperfusion injury. Our results also showed that
      hypercapnic acidosis significantly inhibited the ischemia-reperfusion-induced
      phosphorylation and nuclear translocation of nuclear factor-kappaB. This was
      associated with elevation of inhibitor of nuclear factor-kappaB-alpha level and
      reduced IkappaB kinase-beta phosphorylation, suggesting a suppression of IkappaB
      kinase and thus IkappaB-alpha activation. CONCLUSIONS: Hypercapnic acidosis may
      attenuate lung ischemia-reperfusion injury by suppressing the activation of the
      IkappaB kinase-nuclear factor-kappaB pathway.

PMID- 21946658
TI  - Cardiac function in Vietnamese patients with different dengue severity grades.
AB  - OBJECTIVE: Dengue continues to cause significant global morbidity and mortality.
      Severe disease is characterized by cardiovascular compromise from capillary
      leakage. Cardiac involvement in dengue has also been reported but has not been
      adequately studied. SETTING: Hospital for Tropical Diseases, Ho Chi Minh City,
      Vietnam. SUBJECTS AND DESIGN: Seventy-nine patients aged 8-6 yrs with different
      dengue severity grades were studied using echocardiography including tissue
      Doppler imaging. The patients were split into severity grades: dengue, dengue
      with warning signs, and severe dengue. Changes in cardiac functional parameters
      and hemodynamic indices were monitored over the hospital stay. INTERVENTION:
      None. MEASUREMENTS AND MAIN RESULTS: Patients with severe dengue had worse
      cardiac function compared with dengue in the form of left ventricular systolic
      dysfunction with increased left myocardial performance index (0.58 [0.26-0.80]
      vs. 0.38 [0.22-0.70], p = .006). Septal myocardial systolic velocities were
      reduced (6.4 [4.8-10] vs. 8.1 [6-13] cm/s, p = .01) as well as right ventricular
      systolic (11.4 [7.5-17] vs. 13.5 [10-17] cm/s, p = .016) and diastolic velocities
      (13 [8-23] vs. 17 [12-25] cm/s, p = .0026). In the severe group, these parameters
      improved from hospital admission to discharge; septal myocardial systolic
      velocities to 8.8 (7-11) cm/s (p = .002), right ventricular myocardial systolic
      velocities to 15.0 (11.8-23) cm/s, (p = .003), and diastolic velocity to 21 (11
      25) cm/s (p = .002). Patients with cardiac impairment were more likely to have
      significant pleural effusions. CONCLUSIONS: Patients with severe dengue have
      evidence of systolic and diastolic cardiac impairment with septal and right
      ventricular wall being predominantly affected.

PMID- 21946659
TI  - Prevention of ventilator-associated pneumonia or ventilator-associated
      complications: a worthy, yet challenging, goal.
AB  - Ventilator-associated pneumonia is a difficult diagnosis to establish in the
      critically ill patient because of the presence of underlying cardiopulmonary
      disorders (e.g., pulmonary contusion, acute respiratory distress syndrome,
      atelectasis) and the nonspecific radiographic and clinical signs associated with
      this infection. However, the escalating antimicrobial resistance of the bacterial
      pathogens associated with ventilator-associated pneumonia, as well as with other
      nosocomial infections, has created an imperative to reduce their occurrence and
      the unnecessary use of antibiotics. Hospital-based process improvement
      initiatives aimed at the prevention of ventilator-associated pneumonia, and other
      ventilator-associated complications, have been successfully used despite the
      limitations of clinical criteria for establishing the diagnosis of ventilator
      associated pneumonia. Given current restrictions in hospital resources, absence
      of available new antimicrobial agents, and potential lack of reimbursement for
      patients with development of ventilator-associated pneumonia, hospitals need to
      develop and successfully implement programs aimed at reducing ventilator
      associated pneumonia. The use of evidence-based bundles targeting ventilator
      associated pneumonia seems to be a reasonable first step in addressing this
      important clinical problem.

PMID- 21946660
TI  - Improving long-term outcomes after discharge from intensive care unit: report
      from a stakeholders' conference.
AB  - BACKGROUND: Millions of patients are discharged from intensive care units
      annually. These intensive care survivors and their families frequently report a
      wide range of impairments in their health status which may last for months and
      years after hospital discharge. OBJECTIVES: To report on a 2-day Society of
      Critical Care Medicine conference aimed at improving the long-term outcomes after
      critical illness for patients and their families. PARTICIPANTS: Thirty-one
      invited stakeholders participated in the conference. Stakeholders represented key
      professional organizations and groups, predominantly from North America, which
      are involved in the care of intensive care survivors after hospital discharge.
      DESIGN: Invited experts and Society of Critical Care Medicine members presented a
      summary of existing data regarding the potential long-term physical, cognitive
      and mental health problems after intensive care and the results from studies of
      postintensive care unit interventions to address these problems. Stakeholders
      provided reactions, perspectives, concerns and strategies aimed at improving care
      and mitigating these long-term health problems. MEASUREMENTS AND MAIN RESULTS:
      Three major themes emerged from the conference regarding: (1) raising awareness
      and education, (2) understanding and addressing barriers to practice, and (3)
      identifying research gaps and resources. Postintensive care syndrome was agreed
      upon as the recommended term to describe new or worsening problems in physical,
      cognitive, or mental health status arising after a critical illness and
      persisting beyond acute care hospitalization. The term could be applied to either
      a survivor or family member. CONCLUSIONS: Improving care for intensive care
      survivors and their families requires collaboration between practitioners and
      researchers in both the inpatient and outpatient settings. Strategies were
      developed to address the major themes arising from the conference to improve
      outcomes for survivors and families.

PMID- 21946661
TI  - IL-17 in liver injury: an inflammatory issue?

PMID- 21946662
TI  - In vivo accumulation of T cells in response to IL-2/anti-IL-2 mAb complexes is
      dependent in part on the TNF family ligand 4-1BBL.
AB  - Immune complexes combining IL-2 with particular anti-IL-2 antibodies can be used
      to selectively expand regulatory T cells or memory T cells. Combining IL-2 with
      anti-IL-2 (Clone S4B6) greatly enhances the biological potency of IL-2 in vivo
      leading to selective expansion of CD8 memory T cells and NK cells compared with
      regulatory T cells. Here we show that in vivo administration of IL-2/anti-IL-2
      mAb (IL-2/mAb) complexes induces 4-1BB expression on both adoptively transferred
      antigen-specific memory CD8 T cells as well as on endogenous memory phenotype
      cells. Remarkably, the accumulation of adoptively transferred memory CD8 T cells
      following in vivo IL-2/mAb-complex treatment was found to be dependent in part on
      the presence of 4-1BBL in the host. These effects were independent of IL-2
      induced cell division, suggesting that 4-1BBL-induced survival signals contribute
      to IL-2/mAb-complex-induced T-cell accumulation in vivo.

PMID- 21946663
TI  - Prostaglandin E2 and T cells: friends or foes?
AB  - Our understanding of the key players involved in the differential regulation of T
      cell responses during inflammation, infection and auto-immunity is fundamental
      for designing efficient therapeutic strategies against immune diseases. With
      respect to this, the inhibitory role of the lipid mediator prostaglandin E(2)
      (PGE(2)) in T-cell immunity has been documented since the 1970s. Studies that
      ensued investigating the underlying mechanisms substantiated the suppressive
      function of micromolar concentrations of PGE(2) in T-cell activation,
      proliferation, differentiation and migration. However, the past decade has seen a
      revolution in this perspective, since nanomolar concentrations of PGE(2) have
      been shown to potentiate Th1 and Th17 responses and aid in T-cell proliferation.
      The understanding of concentration-specific effects of PGE(2) in other cell
      types, the development of mice deficient in each subtype of the PGE(2) receptors
      (EP receptors) and the delineation of signalling pathways mediated by the EP
      receptors have enhanced our understanding of PGE(2) as an immune-stimulator.
      PGE(2) regulates a multitude of functions in T-cell activation and
      differentiation and these effects vary depending on the micro-environment of the
      cell, maturation and activation state of the cell, type of EP receptor involved,
      local concentration of PGE(2) and whether it is a homeostatic or inflammatory
      scenario. In this review, we compartmentalize the various aspects of this complex
      relationship of PGE(2) with T lymphocytes. Given the importance of this molecule
      in T-cell activation, we also address the possibility of using EP receptor
      antagonism as a potential therapeutic approach for some immune disorders.

PMID- 21946664
TI  - IL-22 and non-ELR-CXC chemokine expression in chronic hepatitis B virus-infected
      liver.
AB  - Hepatitis B virus infection is still a major global health problem, despite
      decades of research. Interleukin (IL)-22 induces acute phase reactants and
      chemokines, favors anti-microbial defence and protects tissues from damage. IL-22
      is important in chronic skin inflammation, but its role in chronic hepatitis B
      (CHB) is unclear. This study explores the association between intra-hepatic IL-22
      expression, its relevant associated cytokines and the severity of liver
      inflammation/fibrosis in CHB patients. IL-22, IL-17, IL-10, IL-6, non-ELR-CXC
      chemokines (CXCL-9, CXCL-10, CXCL-11), fibroblast growth factors and Kupffer cell
      (KC) numbers were measured in patients with CHB (n=65), acute hepatitis B (AHB;
      n=4), chronic hepatitis C (CHC; n=14) and non-viral hepatitis (n=23), using
      immunohistochemistry. Expression of IL-22, IL-17, IL-10, IL-6, non-ELR-CXC
      chemokines and number of KCs in liver tissues were substantially higher in AHB
      patients than others. In CHB patients, the expression of IL-22, IL-6, CXCL-9 and
      CXCL-10 were significantly higher with alanine aminotransferase (ALT) levels <=
      twice the upper limit of normal (ULN), compared with those with ALT levels >twice
      the ULN, whereas IL-10 and IL-17 showed a reverse pattern. IL-22 was inversely
      (P<0.01), but IL-17 was positively (P<0.05), correlated with the histological
      activity index) in these patients, and a significant negative correlation between
      the fibrosis stage and IL-22 or non-ELR-CXC chemokines was observed. Furthermore,
      immunofluorescent labeling demonstrated a close spatial association of IL-22,
      CXCL-9, -10 or -11 in the CHB liver. We speculate that IL-22 and non-ELR-CXC
      chemokines synergistically may provide protection in liver inflammation/fibrosis
      during CHB infection.

PMID- 21946666
TI  - Reflections on the back forty.

PMID- 21946665
TI  - Chronic myeloid leukemia stem cells in the era of targeted therapies: resistance,
      persistence and long-term dormancy.
AB  - Targeted therapies of chronic myeloid leukemia (CML) using tyrosine kinase
      inhibitors (TKI) have profoundly changed the natural history of the disease with
      a major impact on survival.  Molecular monitoring with BCR-ABL quantification
      shows that a status of undetectable molecular residual disease (UMRD) is obtained
      in a significant minority of patients. However, it remains unclear whether these
      patients are definitively cured of their leukemia. Imatinib mesylate withdrawal
      trials have demonstrated the rapid appearance of the malignant clone in the
      majority of the patients whereas some patients remain in a state of UMRD. It has
      clearly been demonstrated that the most primitive stem cells are refractory to
      all TKIs used in clinical practice. In addition, long-term dormancy is one of the
      most fundamental characteristics of hematopoietic stem cells. In this context, we
      have recently undertaken a systematic analysis of the bone marrow stem cell
      compartment in several patients in durable UMRD. We have demonstrated the long
      term persistence of a considerable amount of BCR-ABL-expressing stem cells, even
      in the absence of relapse. The phenomenon of long-term leukemic stem cell
      dormancy is of major importance in CML and one of the key questions in cancer
      biology in general. We discuss, here, the potential mechanisms, including
      intrinsic and microenvironmental factors, that control the response of leukemic
      stem cells (LSCs) to targeted therapies and potential novel strategies currently
      in progress with a curative intent. Moreover, we propose a molecular evaluation
      of the residual LSC compartment in selected patients in order to develop rational
      TKI-cessation strategies in CML.

PMID- 21946667
TI  - The proteomes of transcription factories containing RNA polymerases I, II or III.
AB  - Human nuclei contain three RNA polymerases (I, II and III) that transcribe
      different groups of genes; the active forms of all three are difficult to isolate
      because they are bound to the substructure. Here we describe a purification
      approach for isolating active RNA polymerase complexes from mammalian cells.
      After isolation, we analyzed their protein content by mass spectrometry. Each
      complex represents part of the core of a transcription factory. For example, the
      RNA polymerase II complex contains subunits unique to RNA polymerase II plus
      various transcription factors but shares a number of ribonucleoproteins with the
      other polymerase complexes; it is also rich in polymerase II transcripts. We also
      describe a native chromosome conformation capture method to confirm that the
      complexes remain attached to the same pairs of DNA templates found in vivo.

PMID- 21946668
TI  - Rapid and robust generation of functional oligodendrocyte progenitor cells from
      epiblast stem cells.
AB  - Myelin-related disorders such as multiple sclerosis and leukodystrophies, for
      which restoration of oligodendrocyte function would be an effective treatment,
      are poised to benefit greatly from stem cell biology. Progress in myelin repair
      has been constrained by difficulties in generating pure populations of
      oligodendrocyte progenitor cells (OPCs) in sufficient quantities. Pluripotent
      stem cells theoretically provide an unlimited source of OPCs, but current
      differentiation strategies are poorly reproducible and generate heterogenous
      populations of cells. Here we provide a platform for the directed differentiation
      of pluripotent mouse epiblast stem cells (EpiSCs) through defined developmental
      transitions into a pure population of highly expandable OPCs in 10 d. These OPCs
      robustly differentiate into myelinating oligodendrocytes in vitro and in vivo.
      Our results demonstrate that mouse pluripotent stem cells provide a pure
      population of myelinogenic oligodendrocytes and offer a tractable platform for
      defining the molecular regulation of oligodendrocyte development and drug
      screening.

PMID- 21946669
TI  - Effect of substituents and hydrogen bonding on barrier heights in dehydration
      reactions of carbon and silicon geminal diols.
AB  - Activation barrier heights for the dehydration reaction of geminal carbinols and
      silanediols R'R"X(OH)(2) (X = C, Si) were estimated at the B3LYP and MP2 levels
      of theory employing Dunning's correlation-consistent triple-zeta basis sets. It
      was shown that the barrier height for carbon derivatives steadily decreases upon
      substitution by R groups, usually termed as electron-donating, such as alkyl and
      amino groups. Substitution by electron-withdrawing groups leads, however, only to
      small changes in barrier heights compared to that of methanediol. A similar
      tendency was also found for silicon derivatives, but high activation barriers of
      this reaction remain even for amino group substituted silanediols. Introduction
      of additional water molecules into the reactive space of carbinol dehydration
      drastically reduces barrier heights and brings the transition state energy for
      methanediol close to the experimental value. The difference between dehydration
      barrier heights for both methanediol and carbinols with electron-rich
      substituents becomes well-defined for dimeric species. The higher acidity of the
      hydroxyl group protons in molecules containing halogens and C==O groups brings
      about a noticeable growth in the dehydration barrier heights of these compounds.
      This difference in barrier heights for oligomeric species may be the reason for
      the stability of carbinols with electron-rich substituents.

PMID- 21946671
TI  - Biophysical assays to probe the mechanical properties of the interphase cell
      nucleus: substrate strain application and microneedle manipulation.
AB  - In most eukaryotic cells, the nucleus is the largest organelle and is typically 2
      to 10 times stiffer than the surrounding cytoskeleton; consequently, the physical
      properties of the nucleus contribute significantly to the overall biomechanical
      behavior of cells under physiological and pathological conditions. For example,
      in migrating neutrophils and invading cancer cells, nuclear stiffness can pose a
      major obstacle during extravasation or passage through narrow spaces within
      tissues.(1) On the other hand, the nucleus of cells in mechanically active tissue
      such as muscle requires sufficient structural support to withstand repetitive
      mechanical stress. Importantly, the nucleus is tightly integrated into the
      cellular architecture; it is physically connected to the surrounding
      cytoskeleton, which is a critical requirement for the intracellular movement and
      positioning of the nucleus, for example, in polarized cells, synaptic nuclei at
      neuromuscular junctions, or in migrating cells.(2) Not surprisingly, mutations in
      nuclear envelope proteins such as lamins and nesprins, which play a critical role
      in determining nuclear stiffness and nucleo-cytoskeletal coupling, have been
      shown recently to result in a number of human diseases, including Emery-Dreifuss
      muscular dystrophy, limb-girdle muscular dystrophy, and dilated
      cardiomyopathy.(3) To investigate the biophysical function of diverse nuclear
      envelope proteins and the effect of specific mutations, we have developed
      experimental methods to study the physical properties of the nucleus in single,
      living cells subjected to global or localized mechanical perturbation. Measuring
      induced nuclear deformations in response to precisely applied substrate strain
      application yields important information on the deformability of the nucleus and
      allows quantitative comparison between different mutations or cell lines
      deficient for specific nuclear envelope proteins. Localized cytoskeletal strain
      application with a microneedle is used to complement this assay and can yield
      additional information on intracellular force transmission between the nucleus
      and the cytoskeleton. Studying nuclear mechanics in intact living cells preserves
      the normal intracellular architecture and avoids potential artifacts that can
      arise when working with isolated nuclei. Furthermore, substrate strain
      application presents a good model for the physiological stress experienced by
      cells in muscle or other tissues (e.g., vascular smooth muscle cells exposed to
      vessel strain). Lastly, while these tools have been developed primarily to study
      nuclear mechanics, they can also be applied to investigate the function of
      cytoskeletal proteins and mechanotransduction signaling.

PMID- 21946672
TI  - Bidirectional regulation of human colonic smooth muscle contractility by
      tachykinin NK(2) receptors.
AB  - In this study, we attempted to clarify the mechanism of tachykinin-induced motor
      response in isolated smooth muscle preparations of the human colon. Fresh
      specimens of normal colon were obtained from patients suffering from colonic
      cancer. Using mucosa-free smooth muscle strips, smooth muscle tension with
      circular direction was monitored isometrically. Substance P (SP), neurokinin A
      (NKA), and neurokinin B (NKB) produced marked contraction. All of these
      contractions were inhibited by saredutant, a selective NK(2)-R antagonist, but
      not by CP122721, a selective NK(1)-R antagonist or talnetant, a selective NK(3)-R
      antagonist. betaAla(8)-NKA(4-10) induced concentration-dependent contraction
      similar to NKA, but Sar(9)-Met(11)-SP and Met-Phe(7)-NKB did not cause marked
      contraction. Colonic contraction induced by betaAla(8)-NKA(4-10) was completely
      blocked by saredutant, but not by atropine. Tetrodotoxin or N(G)-nitro-L-arginine
      methyl ester pretreatment significantly enhanced betaAla(8)-NKA(4-10)-induced
      contraction. Immunohistochemical analysis showed that the NK(2)-R was expressed
      on the smooth muscle layers and myenteric plexus where it was also co-expressed
      with neuronal nitric oxide synthase in the myenteric plexus. These results
      suggest that the NK(2)-R is a major contributor to tachykinin-induced smooth
      muscle contraction in human colon and that the NK(2)-R-mediated response consists
      of an excitatory component via direct action on the smooth muscle and an
      inhibitory component possibly via nitric oxide neurons.

PMID- 21946673
TI  - ACR Appropriateness Criteria(r) postoperative adjuvant therapy in non-small cell
      lung cancer.
AB  - Therapeutic options for postoperative adjuvant treatment for patients with non
      small cell lung cancer (NSCLC) continue to evolve, and may include postoperative
      radiotherapy (PORT) and chemotherapy, alone or in combination. The use of
      platinum-based adjuvant chemotherapy has been demonstrated to confer an
      improvement in overall survival in patients with completely resected, stage N1 or
      N2 NSCLC, in several randomized trials and 2 meta-analyses. Consideration may
      also be given to adjuvant chemotherapy in patients with node-negative NSCLC, when
      the primary tumor is >4 cm, based on subset analyses of recent prospective
      studies. The precise role of PORT is less well defined. Older randomized studies
      indicated that the toxicity of PORT outweighed the potential improvement in local
      control, but studies using more modern radiation techniques show significantly
      reduced toxicity, inferring that select patients may benefit. Relative
      indications for PORT include the presence of mediastinal lymph nodes, positive
      surgical margins, and considerations with regard to the extent and type of
      resection. This study by the lung cancer expert panel of the American College of
      Radiology summarizes the recent evidence-based literature that addresses the use
      of postoperative adjuvant radiotherapy and chemotherapy in patients with NSCLC,
      illustrated with clinical scenarios. The sequencing of radiotherapy and
      chemotherapy is discussed, along with issues regarding radiotherapy dose and
      fractionation, and the appropriate use of intensity modulated radiation therapy
      and particle therapy.

PMID- 21946674
TI  - Wide local excision or mohs micrographic surgery for primary dermatofibrosarcoma
      protuberans.

PMID- 21946676
TI  - Improving cardiovascular risk assessment.

PMID- 21946677
TI  - Musculoskeletal undergraduate curriculum: what is required?

PMID- 21946678
TI  - High calcium scores in patients with a low Framingham risk of cardiovascular
      (CVS) disease: implications for more accurate CVS risk assessment in New Zealand.
AB  - AIMS: New Zealand (NZ) patients are recommended to undergo an 'adjusted'
      Framingham score to assess their cardiovascular (CVS) risk. The current (2009) NZ
      CVS Risk Guideline does not recommend the use of a 'calcium score' as an
      additional risk tool, although it has been shown to be powerfully predictive of
      CVS events above the predictive power of traditional Framingham risk factors.
      Calcium scores of >400 are very strongly predictive of a future CVS event and
      give direct evidence of atheromatous disease in the coronary circulation.
      Identification of people with advanced, premature coronary atheroma would allow
      early treatment of those who may benefit from more vigorous preventative
      strategies, including statin therapy. METHODS: Using a prospectively acquired,
      comprehensive database we audited the first 1000 patients (7 August 2006 to 28
      November 2008) to undergo a 64-slice computed tomographic (CT) cardiac angiogram
      (GE Light Speed), which included a scan for a 'calcium score', at the Mercy
      Hospital, Auckland. We excluded 58 patients who had experienced one or more of a
      previous myocardial infarction (MI) (n=21), coronary artery bypass graft (CABG)
      surgery (n=15), percutaneous coronary intervention (PCI) (n=13) or stroke (n=21)
      and who therefore already had definite evidence of vascular disease and would be
      automatically placed in a high risk strata. We calculated each patient's
      Framingham risk from the original 'Anderson' equation, used by the 1996 NZ CVS
      risk Guideline, and the 'adjusted' Framingham 5-year CVS risk using the NZ
      Guidelines Group 2003/2009 recommendations, and then compared this with the
      observed calcium scores. RESULTS: The mean patient age was 56 (SD 9) years; 364
      (39%) patients were female, 82% patients were Caucasian. 41% were current (4.6%)
      or previous (36%) cigarette smokers, 35% had a history of hypertension, 44%
      hyperlipidaemia and 5.6% had diabetes mellitus. The percentage of patients at
      'low' 5-Year CVS risk (0-10% 5-year risk), using the 1996 and 2003/2009 guideline
      methods, was 78% and 58% respectively. Of patients in these Framingham 'low-risk'
      groups, 10% and 8.8% had a calcium score of >400 Agatston units, indicating that
      they were actually at very high CVS risk, and 203 (28%) and 147 (27%)
      respectively had a calcium score of >100 Agatston units, indicating that they
      were actually at 'high risk' and not 'low risk'. CONCLUSION: Approximately 10% to
      27% of patients with a low CVS risk as assessed by the established Framingham
      equation have a markedly increased calcium score and hence a significantly
      increased risk of a CVS event. Currently promoted methods of risk assessment may
      be inadvertently, falsely re-assuring these patients. Clinicians managing
      patients may consider a calcium score as an additional tool to the standard risk
      assessment strategies.

PMID- 21946679
TI  - Basing musculoskeletal curriculum changes on the opinions of practicing
      physicians.
AB  - AIM: To establish which musculoskeletal conditions are deemed to be the most
      important in clinical practice. To use this information to inform the development
      of a new musculoskeletal curriculum, with emphasis on common and relevant
      conditions. METHODS: A survey listing 29 musculoskeletal conditions was sent to
      150 doctors in Auckland, New Zealand. Doctors from 5 specialties, including
      general practice, were asked to score each condition on a rating scale from 0 to
      7, to determine which conditions were perceived to be the most important as
      encountered in day-to-day clinical practice. RESULTS: The overall response rate
      to the survey was 36% and this was predominantly due to the low response rate
      from general practitioners. Fifteen conditions were given average ratings of
      4.5/7 or greater and the top 5 of these were as follows: prolapsed intervertebral
      disc, hip fracture, mechanical back pain, gout at the great toe and
      osteoarthritis of the hip. CONCLUSION: This study has used a consensus approach
      to identify specific musculoskeletal conditions deemed to be the most important
      in clinical practice. The information obtained can be used for designing a
      contemporary and relevant musculoskeletal medical curriculum.

PMID- 21946680
TI  - Needlestick injuries in a healthcare setting in New Zealand.
AB  - AIM: The aim of this study was to quantify the extent of needlestick
      underreporting, to examine factors which may contribute to underreporting, and to
      optimise the relevant risk management strategy. METHOD: An 11-item structured
      postal questionnaire was adapted from an existing CDC design. RESULTS: The survey
      results showed that 9% of respondents had experienced at least one needlestick
      injury in the past year, and three practitioners had five or more injuries in the
      same period. The overall underreporting rate for needlestick injuries was 33%,
      which is consistent with internationally-reported figures. More than one in six
      respondent doctors (17.8%) had sustained one or more needlestick injuries in the
      past year, compared with nurses (7.6%) or midwives (6.7%). CONCLUSION: The survey
      identified the level of underreporting and the factors that influence needlestick
      reporting. This has resulted in a series of recommendations that will help our
      DHB to formulate an appropriate strategy to manage needlestick incidence and
      impact.

PMID- 21946681
TI  - Healthcare services funded by Counties Manukau District Health Board for people
      in the last year of life.
AB  - INTRODUCTION: The last year of life is often associated with a high level of
      healthcare utilisation and cost. To date, little information is available
      regarding the healthcare utilisation patterns in the last year of life in New
      Zealand. AIM: To describe the healthcare utilisation patterns and costs of the
      residents of Counties Manukau District Health Board (CMDHB) region in the 1-year
      period prior to death in 2008. METHOD: CMDHB residents who died in 2008 were
      identified from the National Mortality Dataset. The health services utilisation
      patterns and costs in the last year of life were derived from National Minimum
      Dataset (NMDS), Pharmaceutical Collection, Laboratory Claims Collection, and
      National Non-Admitted Patient Collection via encrypted NHI linkage. RESULTS:
      Forty percent of all deaths in 2008 in CMDHB occurred in a publicly funded
      hospital. Just over 80% of people had at least one inpatient hospital stay in the
      last year of life. More than 75% of the healthcare costs funded by CMDHB in the
      last year of life were related to inpatient hospitalisations. The average
      cumulative length of inpatient stay over the year in the people who had an
      inpatient event was 20.6 days. Outpatient, pharmaceutical, and laboratory
      services were received by 84%, 91%, and 86% of people respectively in their last
      year of life. CONCLUSION: Consistent with the international literature, this
      study found that CMDHB residents in the last year of life have a high level of
      health service utilisation. Decisions about the appropriate use of high cost
      health services in people towards the end of life can be extremely challenging.
      These decisions are resource allocation decisions as well as clinical decisions
      and should be based on clinical factors, cost utilities, and patient, family, and
      society's expectations.

PMID- 21946683
TI  - Citizenship, work, welfare, education and health in New Zealand.
AB  - Access to excellent, unconstrained and timely health care is considered a
      birthright by most New Zealanders. However, there are shortcomings in some health
      services, especially in mental health and rehabilitation, and these not only have
      an adverse personal impact but also challenge the sustainability of the national
      welfare system. There are insufficient well-trained people who can manage 'care'
      in line with either generic best practice or Whanau Ora ideology. An important
      and core reform is for a coordination of relevant programmes in education,
      health, justice and welfare, and for both shared accountabilities and linked
      governance.

PMID- 21946682
TI  - Neuro-ophthalmic manifestations and outcomes of pituitary apoplexy--a life and
      sight-threatening emergency.
AB  - OBJECTIVE: To report the neuro-ophthalmic manifestations and outcomes in patients
      with pituitary apoplexy. METHOD: Retrospective chart review. RESULTS: 23 patients
      were identified (17 men, mean age 54.1 years (range 23-86 years). The onset was
      abrupt in 22 patients; one patient had a subclinical presentation. Headache was
      the commonest presenting symptom (82.6%, 19/23). Neuro-ophthalmic manifestations
      were present in more than three-quarters of the patients (82.6%, 19/23). At
      presentation, 55 % (11/20), 47.6 % (10/21) and 60.9 % (14/23) of the patients had
      reduced visual acuity, field defects and cranial nerve palsies respectively.
      Management was conservative in 4 patients and surgical in 18 patients; one
      patient died shortly after presentation. The median follow up period was 10.5
      months (22 patients, range 0.2-168 months).  At final follow up, improvement was
      present in 100% of the patients with reduced acuity (8/8) and ocular palsy
      (13/13) and 81.8% of patients with field deficits (9/11). Age, sex, presence of
      precipitating factors and timing of surgery did not have an impact on neuro
      ophthalmic recovery. CONCLUSION: Pituitary apoplexy should be considered in any
      patient with abrupt onset of neuro-ophthalmic deficits. Prompt medical and
      surgical management is lifesaving and can lead to significant improvement in
      visual and cranial nerve deficits.

PMID- 21946684
TI  - ACC and back injuries: the relevance of pre-existing asymptomatic conditions
      revisited.
AB  - The application of the New Zealand Accident Compensation Corporation (ACC)
      legislation in the management of patients who sustain back injuries requires a
      detailed knowledge of the pathogenesis of tissue injury, and the natural history
      of ageing and related conditions, so that the application of the ACC Act(s) is
      appropriate. We have reviewed the new information published in the last decade,
      and updated the previous knowledge basis in these fields, so as to assist the
      interpretation of the Act(s).

PMID- 21946685
TI  - What does degeneration mean? The use and abuse of an ambiguous word.
AB  - The use of the word degeneration, particularly in the compensation arena, is not
      recommended. It is imprecise and is interpreted in different ways by
      radiologists, clinicians and insurers. Insurers use the word to conclude that any
      so called degenerative changes mean that there is age causation so that
      compensation can be denied. These changes can be caused by single or multiple
      injuries continuing heavy work and other causes. Each risk factor should be
      carefully assessed in each case.

PMID- 21946686
TI  - Ulnar artery ischaemia following corticosteroid injection for carpal tunnel
      syndrome.
AB  - A 36-year-old female with known bilateral carpal tunnel syndrome was admitted to
      hospital and given a steroid injection on the ulnar side in her right hand. She
      suffered immediate ischaemia of the 3rd, 4th, and 5th fingers. Imaging showed
      decreased flow in the 4th and 5th phalageal arteries. Treatment with iloprost
      infusion commenced 7 days after the injury, with moderate improvement and further
      managed with a carpal tunnel release. This case report sheds light on an unusual
      yet very important complication of carpal tunnel management.

PMID- 21946688
TI  - Deliverance from exophthalmic goitre deaths.

PMID- 21946687
TI  - Medical image. Takayasu's arteritis.

PMID- 21946689
TI  - Pathognomonic rash.

PMID- 21946690
TI  - Anterior cruciate ligament reconstructions, the debate continues--with another
      response by Assoc Prof Hooper.

PMID- 21946691
TI  - Is the quality of evidence for air quality standards adequate?

PMID- 21946692
TI  - Government response to air pollution articles in NZMJ.

PMID- 21946693
TI  - Angiotensin II-dependent hypertension causes reversible changes in the platelet
      proteome.
AB  - OBJECTIVE: Hypertension is a risk factor for arterial thrombosis. We investigated
      the effects of angiotensin II (ANG II)-dependent hypertension on the platelet
      proteome. METHODS AND RESULTS: Hypertension was induced in cyp1a1ren-2 transgenic
      rats by feeding indole-3-carbinol (n = 10) and in Fischer 344 rats by
      subcutaneously infusing ANG II (n = 7). After 14 days of hypertension (SBP 180
      mmHg) and 10 days after normalization of blood pressure, changes in the platelet
      proteome were assessed by two-dimensional differential in-gel electrophoresis. In
      a subset of animals (n = 4), repeated blood withdrawals were performed. Of 1040
      protein spots, 45 displayed hypertension-associated changes (>1.5-fold, P < 0.01)
      in both models (34 increased, 11 decreased). All were reversible within 10 days.
      Thirty-eight spots were identified by mass spectrometry and assigned to 20
      distinct proteins. The majority of spots with increased intensity constituted
      protein fragments. Repeated blood withdrawals and stimulation of
      megakaryocytopoiesis by a thrombopoietin receptor agonist induced changes in the
      same protein spots but in the opposite direction to those induced by ANG II
      dependent hypertension. CONCLUSION: ANG II-dependent hypertension is associated
      with enhanced protein degradation in platelets. As these changes are reversible,
      the proteins identified might be used to develop a biomarker for monitoring
      recent blood pressure history.

PMID- 21946694
TI  - Influence of the recommendations on the implementation of home blood pressure
      measurement by French general practitioners:  a 2004-2009 longitudinal survey.
AB  - OBJECTIVES: To assess the implementation of home blood pressure measurement
      (HBPM) by French general practitioners (GPs) in current practice in 2009 and to
      assess the evolution of practices between 2004 and 2009; the perceived benefits
      and limitations of the method; and the adherence to methodological European
      [European Society of Hypertension (ESH) 2007] or French [La Haute Autorite de
      Sante (HAS) 2005] recommendations. METHOD: Two phone surveys on a representative
      random sample of French GPs in 2004 and then in 2009. RESULTS: Five hundred and
      forty and 801 GPs were contacted in 2004 and 2009, respectively, in which 511 and
      500 participated, including the same 214 in both surveys. The proportion of HBPM
      users increased between 2004 (70%) and 2009 (92%) (P < 0.0001). The majority
      still remained occasional users (71%), whereas a minority (21%) used this method
      nearly systematically in 2009. In 2009, both users and nonusers highlighted the
      lack of reliability of devices (19 and 47%) and lack of patient reliability (27
      and 24%) and patient anxiety (47 and 29%). The expected benefit was primarily the
      detection of white-coat effect (70%), therapeutic adaptation (36%), diagnostic
      aid (25%), and better compliance with treatment (14%). Masked hypertension
      detection (2%) and prognostic interest (0.7%) were marginal. The GPs declared
      rarely adopting ESH methodology (3% of users), but more often HAS methodology
      (33%). Adherence to the complete methodology was rare (absolute adherence <1%),
      but more often 'minimal' (three morning and evening measurements, at least 3 days
      with an upper arm cuff: 17%). Contraindications of HBPM use were not known.
      CONCLUSION: Despite greater use of HBPM after enactment of the recommendations,
      the methodology is not strictly implemented, making its diagnostic and prognostic
      value uncertain.

PMID- 21946695
TI  - Role of angiotensin-converting enzyme 2 in cardiac hypertrophy induced by nitric
      oxide synthase inhibition.
AB  - OBJECTIVE: Angiotensin-converting enzyme 2 (ACE2) generates angiotensin-(1-7)
      [Ang-(1-7)], a peptide highlighted as exerting a pivotal role in cardiovascular
      remodeling. Moreover, the ACE2/Ang-(1-7)/Mas axis directly activates endothelial
      nitric oxide (NO) synthase and NO generation in the heart. However, the role of
      ACE2 in cardiovascular remodeling induced by persistent inhibition of NO under
      chronic activation of the renin-angiotensin system (RAS) remains poorly
      understood. METHODS AND RESULTS: Chimeric hypertensive mice that exhibit
      activation of the human RAS were produced by mating human renin (hRN) and human
      angiotensinogen (hANG) transgenic mice. Persistent NO inhibition with NG-nitro-L
      arginine methyl ester (L-NAME) was started at 8 weeks of age for 4 weeks. After
      administration of L-NAME, blood pressure (BP) markedly increased in the chimeric
      mice (hRN/hANG-Tg), whereas wild-type mice (C57BL/6J) showed little increase in
      BP. Cardiovascular remodeling with enhanced oxidative stress in hRN/hANG-Tg was
      markedly accelerated by NO inhibition compared with that in wild-type mice.
      Moreover, ACE2 mRNA expression and activity in cardiac tissue were markedly
      reduced in L-NAME-treated hRN/hANG-Tg. Co-administration of an angiotensin II
      type 1 (AT1) receptor blocker (ARB), olmesartan, inhibited L-NAME-induced
      cardiovascular remodeling and improved the reduction in cardiac ACE2. The
      preventive effect of olmesartan on cardiac hypertrophy was blunted by co
      administration of a selective Ang-(1-7) antagonist, [D-Ala7]-Ang-(1-7).
      CONCLUSION: Our findings demonstrate that cardiovascular remodeling induced by
      persistent NO inhibition was enhanced in hRN/hANG-Tg. An ARB, olmesartan, blunted
      cardiac remodeling induced by NO inhibition with RAS activation partially through
      the ACE2/Ang-(1-7)/Mas axis in addition to directly through its classical ACE/Ang
      II/AT1 receptor axis-blocking action.

PMID- 21946696
TI  - Health-related quality of life and awareness of hypertension.
AB  - BACKGROUND: It has been shown that individuals with hypertension have poorer
      health-related quality of life (HRQoL) than normotensive individuals. However,
      little is known about the impact of high blood pressure and the awareness to have
      hypertension on HRQoL. METHODS: In this cross-sectional population-based study,
      we evaluated 901 cardiovascular risk patients aged 45 to 70 years without serious
      comorbidities. Hypertension was detected in 497 (55%) of the patients, in whom
      137 (28%) had previously undiagnosed hypertension confirmed with home blood
      pressure measurement. Before the diagnosis of hypertension was made, the patients
      filled Short-Form Health Survey (SF-36) to assess their HRQoL. Glucose
      homeostasis was assessed with 2  h oral glucose tolerance test. RESULTS: Patients
      who were aware of their hypertension had lower scores in physical functioning and
      general health than patients without hypertension and patients who were unaware
      of hypertension. There were no differences for mental components of SF-36 between
      these study groups. The prevalence of obesity and newly diagnosed type 2 diabetes
      was higher in patients with known hypertension than among other study groups.
      CONCLUSION: Impaired HRQoL in hypertensive patients might be secondary to the
      awareness of hypertension, adverse drug effects, newly diagnosed type 2 diabetes
      or obesity, not high blood pressure per se.

PMID- 21946697
TI  - Detection of irregular patterns of myocardial contraction in patients with
      hypertensive heart disease:  a two-dimensional ultrasound speckle tracking study.
AB  - OBJECTIVE: To evaluate the effect of myocardial hypertrophy in patients with
      arterial hypertension on regional myocardial function and left ventricular twist.
      METHODS: Eighty patients with normal coronary angiograms and ejection fraction
      higher than 55% were divided according to left ventricular mass indexed to body
      height (LVMH) into a group with and without left ventricular hypertrophy (LVH).
      The absolute values and time-to-peak values of overall strain (S), systolic (SRS)
      and early diastolic strain rate (SRE) were measured in longitudinal,
      circumferential and radial directions using two-dimensional speckle tracking
      echocardiography. Left ventricular twist and twist rate curves were calculated
      from rotation curves obtained from apical and basal parasternal short-axis
      planes. RESULTS: In the patient group with LVH, SRS and SRE, quantified in
      longitudinal and circumferential direction, were lower compared with the group
      without LVH. In addition, systolic twist rate and diastolic untwist rate were
      significantly lower in this patient group, too. No differences between patients
      groups were found for peak overall S measured in any direction or left
      ventricular twist. LVMH correlated significantly with longitudinal SRS (r = 0.48,
      P < 0.001), longitudinal SRE (r =  -0.48, P < 0.001), systolic twist rate (r =
      0.37, P = 0.006) and diastolic untwist rate (r =  -0.27, P = 0.046). CONCLUSION:
      In conclusion, LVH in patients with arterial hypertension predominantly affected
      longitudinal and circumferential deformation rate. Moreover, LVH resulted in a
      significant reduction of systolic twist rate and diastolic untwist rate, whereas
      overall left ventricular twist angle was not influenced by LVMH.

PMID- 21946699
TI  - Oligomeric Group 13 hydroxide compounds--a rare but varied class of molecules.
AB  - This tutorial review surveys the wide variety of oligomeric hydroxide structures
      formed from aluminum, gallium, and indium. Both inorganic and ligand-supported
      structures are reviewed, providing a leading introduction to this research area.
      In addition to homometallic clusters comprising only one metal type, a series of
      heterometallic structures are described. This review highlights the synthesis and
      characterization of these nanoscale cluster compounds that have implications in a
      variety of fields, including catalysis, mineral mimicry, environmental chemistry,
      geochemistry, materials science, and semiconductors.

PMID- 21946698
TI  - Characterization of hotspots in a highly enhancing SERS substrate.
AB  - Vapor deposition of silver and gold onto a porous anodized aluminum oxide
      template is shown to produce a SERS substrate with an average surface enhancement
      factor of 10(7)-10(8). The high level of enhancement is explored using a
      combination of dark-field Rayleigh scattering and Raman spectroscopy and imaging.
      The scattering spectrum of the surface indicates a Plasmon resonance at 633 nm
      and dark-field imaging shows a relatively uniform scattering intensity at this
      wavelength. These measurements are consistent with the uniform enhanced Raman
      intensity observed in Raman maps of the substrate. Scanning electron microscopy
      shows the surface exhibits heterogeneous nanostructures with diameters of
      approximately 100 nm, the size of the pores in the template. Our measurements
      indicate that interactions between adjacent structures forming junctions and
      crevices likely give rise to a high density of hotspots, which provide the
      extraordinary SERS enhancement. The advantage of substrates prepared in this way
      is the reproducibly dense distribution of hotspots across the surface, increasing
      the likelihood that an analyte will experience the largest enhancement.

PMID- 21946700
TI  - Thin-cap fibroatheroma as high-risk plaque for microvascular obstruction in
      patients with acute coronary syndrome.
AB  - BACKGROUND: Plaque contents can cause microvascular impairment, which is an
      important determinant of clinical outcomes in patients with acute coronary
      syndrome (ACS). We hypothesized that percutaneous coronary intervention (PCI) for
      thin-cap fibroatheroma (TCFA) could easily disrupt the fibrous cap and expose the
      contents of plaque to coronary flow, possibly resulting in microvascular
      obstruction (MVO). The purpose of this study was to investigate whether TCFA was
      associated with MVO after PCI in patients with ACS. METHODS AND RESULTS: We
      enrolled 115 patients with ACS who were successfully recanalized with PCI. The
      patients were divided into a ruptured plaque group (n=59), a nonrupture with TCFA
      group (n=21), and a nonrupture and non-TCFA group (n=35), according to optical
      coherence tomography findings of the culprit lesion. Using contrast-enhanced MRI,
      we assessed MVO. There were no statistically significant differences in patient
      characteristics. The nonrupture with TCFA group more frequently presented MVO
      (ruptured plaque, 27%; versus nonrupture with TCFA, 43%; versus non-TCFA and
      nonrupture, 9%; P=0.012). The prevalence of MVO increases as cap thickness
      decreases. CONCLUSIONS: TCFA is more frequently associated with MVO after PCI.
      TCFA is a high-risk plaque for MVO after PCI in patients with ACS.

PMID- 21946701
TI  - Quantitative assessment of artifacts on cardiac magnetic resonance imaging of
      patients with pacemakers and implantable cardioverter-defibrillators.
AB  - BACKGROUND: The safety and clinical utility of MRI at 1.5 T in patients with
      cardiac implantable devices such as pacemakers (PM) and implantable cardioverter
      defibrillators (ICD) have been reported. This study aims to evaluate the extent
      of artifacts on cardiac magnetic resonance (CMR) in patients with PM and ICD
      (PM/ICD). METHODS AND RESULTS: A total of 71 CMR studies were performed with an
      established safety protocol in patients with prepectoral PM/ICD. The artifact
      area around the PM/ICD generator was measured in all short-axis (SA), horizontal
      (HLA), and vertical long-axis (VLA) SSFP cine planes. The location and extent of
      artifacts were also assessed in all SA (20 sectors per plane), HLA, and VLA (6
      sectors per plane) late gadolinium-enhanced CMR (LGE-CMR) planes. The artifact
      area on cine CMR was significantly larger with ICD versus PM generators in each
      plane (P<0.001, respectively). In patients with left-sided ICD or biventricular
      ICD systems, the percentages of sectors with any artifacts on LGE-CMR were 53.7%,
      48.0%, and 49.2% in SA, HLA, and VLA planes, respectively. Patients with left
      sided PM or right-sided PM/ICD had fewer artifacts. Anterior and apical regions
      were severely affected by artifact caused by left-sided PM/ICD generators.
      CONCLUSIONS: In contrast to patients with right-sided PM/ICD and left-sided PM,
      the anterior and apical left ventricle can be affected by susceptibility
      artifacts in patients with left-sided ICD. Artifact reduction methodologies will
      be necessary to improve the performance of CMR in patients with left sided ICD
      systems.

PMID- 21946702
TI  - Rapid detection of coronary artery stenoses with real-time perfusion
      echocardiography during regadenoson stress.
AB  - BACKGROUND: Real-time myocardial contrast echocardiography permits the detection
      of myocardial perfusion abnormalities during stress echocardiography, which may
      improve the accuracy of the test in detecting coronary artery stenoses. We
      hypothesized that this technique could be used after a bolus injection of the
      selective A2A receptor agonist regadenoson to rapidly and safely detect coronary
      artery stenoses. METHODS AND RESULTS: In 100 patients referred for quantitative
      coronary angiography, real-time myocardial contrast echocardiography was
      performed during a continuous intravenous infusion of 3% Definity at baseline and
      at 2-minute intervals for up to 6 minutes after a regadenoson bolus injection
      (400 MUg). Myocardial perfusion was assessed by examination of myocardial
      contrast replenishment after brief high mechanical index impulses. A perfusion
      defect was defined as a delay (>2 seconds) in myocardial contrast replenishment
      in 2 contiguous segments. Wall motion was also analyzed. The overall
      sensitivity/specificity/accuracy for myocardial perfusion analysis in detecting a
      >50% diameter stenosis was 80%/74%/78%, whereas for wall motion analysis it was
      60%/72%/66% (P<0.001 for differences in sensitivity). Sensitivity for myocardial
      perfusion analysis was highest on images obtained during the first 2 minutes
      after regadenoson bolus (P<0.001 compared with wall motion), whereas wall motion
      sensitivity was highest at the 4-to-6-minute period after the bolus. No
      significant side effects occurred after regadenoson bolus injection. CONCLUSIONS:
      Regadenoson real-time myocardial contrast echocardiography appears to be a
      feasible, safe, and rapid noninvasive method for the detection of significant
      coronary artery stenoses.

PMID- 21946703
TI  - Association of imaging markers of myocardial fibrosis with metabolic and
      functional disturbances in early diabetic cardiomyopathy.
AB  - BACKGROUND: Metabolic and vascular disturbances contribute to diabetic
      cardiomyopathy, but the role of interstitial fibrosis in early disease is
      unproven. We sought to assess the relationship between imaging markers of diffuse
      fibrosis and myocardial dysfunction and to link this to possible causes of early
      diabetic cardiomyopathy. METHODS AND RESULTS: Hemodynamic and metabolic data were
      measured in 67 subjects with type 2 diabetes mellitus (age 60+/-10 years) with no
      cardiac symptoms. Myocardial function was evaluated with standard
      echocardiography and myocardial deformation; ischemia was excluded by exercise
      echocardiography. Calibrated integrated backscatter was calculated from
      parasternal long-axis views. T1 mapping was performed after contrast with a
      modified Look-Locker technique using saturation recovery images. Amino-terminal
      propeptides of procollagens type I and III, as well as the carboxy-terminal
      propeptide of procollagen type I, were assayed to determine collagen turnover.
      Subjects with abnormal early diastolic tissue velocity (E(m)) had shorter
      postcontrast T1 values (P=0.042) and higher calibrated integrated backscatter
      (P=0.007). They were heavier (P=0.003) and had worse exercise capacity (P<0.001),
      lower insulin sensitivity (P=0.003), and blunted systolic tissue velocity
      (P=0.05). Postcontrast T1 was associated with diastolic dysfunction (E(m) r=0.28,
      P=0.020; E/E(m) r=-0.24, P=0.049), impaired exercise capacity (r=0.30, P=0.016),
      central adiposity (r=-0.26, P=0.046), blood pressure (systolic r=-0.30, P=0.012;
      diastolic r=-0.49, P<0.001), and insulin sensitivity (r=0.30, P=0.037). The
      association of T1 with E/E(m) (beta=-0.31, P=0.017) was independent of blood
      pressure and metabolic disturbance. Amino-terminal propeptide of procollagens
      type III was linked to diastolic dysfunction (E(m) r=-0.32, P=0.008) and
      calibrated integrated backscatter (r=0.30, P=0.015) but not T1 values.
      CONCLUSIONS: The association between myocardial diastolic dysfunction,
      postcontrast T1 values, and metabolic disturbance supports that diffuse
      myocardial fibrosis is an underlying contributor to early diabetic
      cardiomyopathy.

PMID- 21946705
TI  - Can body fat distribution, adiponectin levels and inflammation explain
      differences in insulin resistance between ethnic Chinese, Malays and Asian
      Indians?
AB  - OBJECTIVE: Diabetes in Asia constitutes approximately half of the global burden.
      Although insulin resistance and incidence of type 2 diabetes differ substantially
      between ethnic groups within Asia, the reasons for these differences are poorly
      understood. We evaluated to what extent body fatness, adiponectin levels and
      inflammation mediate the relationship between ethnicity and insulin resistance in
      an Asian setting. DESIGN: Cross-sectional population-based study. SUBJECTS: In
      total, 4136 adult Chinese, Malays and Asian Indians residing in Singapore.
      MEASUREMENTS: Insulin resistance was assessed using homeostasis model assessment
      (HOMA-IR) and systemic inflammation by C-reactive protein (CRP). Data were
      analyzed using path analysis. RESULTS: HOMA-IR was highest in Asian Indians,
      intermediate in Malays and lowest in Chinese (P<0.001). The difference in HOMA-IR
      between Malays and Chinese disappeared after adjusting for body mass index (BMI).
      For the comparison of Asian Indians with Chinese, the association between
      ethnicity and HOMA-IR was mediated by BMI (men: 32.9%; women: 48.5%), BMI
      adjusted waist circumference (men: 6.1%; women: 3.5%), and CRP (men: 5.1%; women:
      5.6%), and unidentified factors (men: 47.2%; women: 26.5%). Part of the mediating
      effects of body fatness was indirect through effects of body fatness on CRP and
      adiponectin concentrations. CONCLUSION: Mediators of ethnic differences in
      insulin resistance differed markedly depending on the ethnic groups compared.
      General adiposity explained the difference in insulin resistance between Chinese
      and Malays, whereas abdominal fat distribution, inflammation and unexplained
      factors contributed to excess insulin resistance in Asian Indians as compared
      with Chinese and Malays. These findings suggest that interventions targeting
      excess weight gain can reduce ethnic disparities in insulin resistance among
      Asian Indians, Chinese and Malays.

PMID- 21946706
TI  - The association between obesity and mortality in the elderly differs by serum
      concentrations of persistent organic pollutants: a possible explanation for the
      obesity paradox.
AB  - OBJECTIVE: Numerous studies have documented an obesity paradox in which the
      overweight and obese elderly have a better prognosis than those with ideal body
      weight. Good prognosis among the overweight or obese elderly may reflect the
      relative safety of storing the harmful lipophilic chemicals, known as persistent
      organic pollutants (POPs), in adipose tissue rather than in other critical
      organs. Therefore, we hypothesized lower mortality among the obese elderly with a
      higher body burden of POPs, but this pattern may not exist among the obese
      elderly with a lower body burden of POPs. PARTICIPANTS: Using the National Health
      and Nutrition Examination Survey (NHANES) 1999-2004 study with a mean 4.2-year
      follow-up, we tested whether the association between fat mass and total mortality
      in 635 (652 for organochlorine pesticides) elderly participants aged >=70 years
      differed depending on serum concentrations of 23 POPs. RESULTS: There were
      statistically significant interactions between fat mass and POPs in predicting
      total mortality. In those with low POP concentrations, there was no obesity
      paradox; mortality increased with fat mass (hazard ratios about 2-3 in the
      highest vs. lowest quintile of fat mass). However, consistent with an obesity
      paradox, these patterns completely disappeared in those with high POP
      concentrations. Compared with the lowest quintile of fat mass, statistically
      significantly lower mortality was observed in the elderly in the third to fifth
      quintiles of fat mass. In the case of polychlorinated biphenyls, the mortality in
      the highest quintile of fat mass was only one-fifth of that in the lowest
      quintile. CONCLUSION: These findings are consistent with our hypothesis that
      adipose tissue provides relatively safe storage of toxic lipophilic chemicals, a
      phenomenon that could explain the obesity paradox. Although weight loss may be
      beneficial among the obese elderly with low POP concentrations, weight loss in
      the obese elderly with higher serum concentrations of POPs may carry some risk.

PMID- 21946707
TI  - Effect of diet composition on energy expenditure during weight loss: the POUNDS
      LOST Study.
AB  - BACKGROUND: Weight loss reduces energy expenditure, but the contribution of
      different macronutrients to this change is unclear. HYPOTHESIS: We tested the
      hypothesis that macronutrient composition of the diet might affect the
      partitioning of energy expenditure during weight loss. DESIGN: A substudy of 99
      participants from the Preventing Overweight Using Novel Dietary Strategies
      (POUNDS LOST) trial had total energy expenditure (TEE) measured by doubly labeled
      water, and resting energy expenditure (REE) measured by indirect calorimetry at
      baseline and repeated at 6 months in 89 participants. Participants were randomly
      assigned to one of four diets with either 15 or 25% protein and 20 or 40% fat.
      RESULTS: TEE and REE were positively correlated with each other and with fat-free
      mass and body fat, at baseline and 6 months. The average weight loss of 8.1 +/-
      0.65 kg (least-square mean +/- s.e.) reduced TEE by 120 +/- 56  kcal per day and
      REE by 136 +/- 18 kcal per day. A greater weight loss at 6 months was associated
      with a greater decrease in TEE and REE. Participants eating the high-fat diet
      (HF) lost significantly more fat-free mass (1.52 +/- 0.55 kg) than the low-fat
      (LF) diet group (P<0.05). Participants eating the LF diet had significantly
      higher measures of physical activity than the HF group. CONCLUSION: A greater
      weight loss was associated with a larger decrease in both TEE and REE. The LF
      diet was associated with significant changes in fat-free body mass and energy
      expenditure from physical activity compared with the HF diet.

PMID- 21946708
TI  - Nanowired three-dimensional cardiac patches.
AB  - Engineered cardiac patches for treating damaged heart tissues after a heart
      attack are normally produced by seeding heart cells within three-dimensional
      porous biomaterial scaffolds. These biomaterials, which are usually made of
      either biological polymers such as alginate or synthetic polymers such as
      poly(lactic acid) (PLA), help cells organize into functioning tissues, but poor
      conductivity of these materials limits the ability of the patch to contract
      strongly as a unit. Here, we show that incorporating gold nanowires within
      alginate scaffolds can bridge the electrically resistant pore walls of alginate
      and improve electrical communication between adjacent cardiac cells. Tissues
      grown on these composite matrices were thicker and better aligned than those
      grown on pristine alginate and when electrically stimulated, the cells in these
      tissues contracted synchronously. Furthermore, higher levels of the proteins
      involved in muscle contraction and electrical coupling are detected in the
      composite matrices. It is expected that the integration of conducting nanowires
      within three-dimensional scaffolds may improve the therapeutic value of current
      cardiac patches.

PMID- 21946710
TI  - Gene flow in a Yersinia pestis vector, Oropsylla hirsuta, during a plague
      epizootic.
AB  - BACKGROUND & OBJECTIVES: Appreciating how Yersinia pestis, the etiological agent
      of plague, spreads among black - tailed prairie dog (Cynomys ludovicianus)
      colonies (BTPD), is vital to wildlife conservation programs in North American
      grasslands. A little - studied aspect of the system is the role of Y. pestis
      vectors, i.e. fleas, play in the spreading of plague in natural settings. We
      investigated the genetic structure and variability of a common prairie dog flea
      (Oropsylla hirsuta) in BTPD colonies in order to examine dispersal patterns.
      Given that this research took place during a widespread plague epizootic, there
      was the added advantage of gaining information on the dynamics of sylvatic
      plague. METHODS & RESULTS: Oropsylla hirsuta were collected from BTPD burrows in
      nine colonies from May 2005 to July 2005, and eight polymorphic microsatellite
      markers were used to generate genotypic data from them. Gene flow estimates
      revealed low genetic differentiation among fleas sampled from different colonies.
      NestedPCR plague assays confirmed the presence of Y. pestis with the average Y.
      pestis prevalence across all nine colonies at 12%. No significant correlations
      were found between the genetic variability and gene flow of O. hirsuta and Y.
      pestis prevalence on a per -colony basis. CONCLUSION: Oropsylla hirsuta dispersal
      among BTPD colonies was high, potentially explaining the rapid spread of Y.
      pestis in our study area in 2005 and 2006.

PMID- 21946709
TI  - Unity quantum yield of photogenerated charges and band-like transport in quantum
      dot solids.
AB  - Solid films of colloidal quantum dots show promise in the manufacture of
      photodetectors and solar cells. These devices require high yields of
      photogenerated charges and high carrier mobilities, which are difficult to
      achieve in quantum-dot films owing to a strong electron-hole interaction and
      quantum confinement. Here, we show that the quantum yield of photogenerated
      charges in strongly coupled PbSe quantum-dot films is unity over a large
      temperature range. At high photoexcitation density, a transition takes place from
      hopping between localized states to band-like transport. These strongly coupled
      quantum-dot films have electrical properties that approach those of crystalline
      bulk semiconductors, while retaining the size tunability and cheap processing
      properties of colloidal quantum dots.

PMID- 21946711
TI  - Insecticide - treated bednet ownership and utilization in Rivers State, Nigeria
      before a state-wide net distribution campaign.
AB  - BACKGROUND & OBJECTIVES: Malaria presents a huge health and economic burden to
      families living in malaria endemic areas. The use of insecticide-treated nets
      (ITNs) is one of the global strategies in decreasing the malaria burden on
      vulnerable populations. The use of ITNs reduces clinical malaria by over 50% and
      all cause mortality in children by 15-30% when the overall population coverage is
      >70%. This study was aimed at establishing the level of household insecticide 
      treated bednet ownership and utilization in Rivers State, Nigeria before a
      statewide scale -up distribution campaign. STUDY DESIGN: A descriptive, cross -
      sectional study was carried out in the Rivers State in November 2008 among
      household heads or their proxies to serve as a pre -intervention baseline for the
      scale -up distribution of insecticide treated bednets in the state. The
      households were selected by a multi -staged sampling technique: first stage being
      the selection of Local Government Areas (LGAs) from Senatorial districts, second
      stage the selection of communities from LGAs and final stage the selection of
      households. Data were collected using a questionnaire adapted from the WHO/FMoH
      and analyzed using the Epi -Info version 6.04d statistical software package.
      Hypothesis tests were conducted to compare summary statistics at 95% significance
      level. RESULTS: A total of 811 household heads or their proxies were interviewed.
      Their age ranged between 20 and 70 yr, with a mean of 47.96 +/- 4.39 yr. The
      study showed that although 552 (68.1%) of the households owned bednets, only 245
      (30.2%, 95% CI=27.1-33.5) of them owned long -lasting insecticidal nets (LLINs).
      Similarly, only 37.2% of those who owned ITNs slept under them the night
      preceding the survey. CONCLUSION: Household ITN ownership and utilization were
      low in the state. Incorporating behavour change communication package as part of
      the ITN distribution intervention is advocated to increase ITNs utilization in
      the state.

PMID- 21946712
TI  - Evaluation of the impact of ZeroFly(r), an insecticide incorporated plastic
      sheeting  on malaria incidence in two temporary labour shelters in  India.
AB  - BACKGROUND & OBJECTIVES: Prevention of malaria is a major technical and
      operational problem in displaced and mobile populations such as refugee camps and
      temporary labour settlements. Insecticide incorporated plastic sheeting is a new
      technology to control mosquitoes in emergency shelters and also temporary
      habitations at different locations. In view of this, efficacy of ZeroFly(r) , an
      insecticide incorporated plastic sheeting (factory treated with deltamethrin 2.0
      g/kg or 265 mg/m2 ) was evaluated for its efficacy against malaria vectors and
      its impact on malaria incidence in temporary labour settlements in two urban
      areas in India. METHODS: This trial was conducted in two labour settlements in
      two urban areas, Delhi and Noida (U.P.), India with ~ 250 populations. In an
      area, two localities were selected for intervention with ZeroFly and untreated
      plastic sheets (control). Entomological and epidemiological data were collected
      using standard methods for one year. RESULTS: Baseline studies on the
      susceptibility of mosquitoes in Delhi and Noida areas revealed 100%
      susceptibility of the malaria vector species Anopheles culicifacies and An.
      stephensi to deltamethrin. Cone bioassay tests performed against An. culicifacies
      and An. stephensi to determine the efficacy of ZeroFly sheets showed 100%
      mortality against An. culicifacies and An. stephensi with 3 min exposure and
      after 24 h recovery period. Against Culex quinquefasciatus and housefly 100%
      mortality was obtained after 30 min of exposure period. Intervention with the
      ZeroFly plastic sheets resulted in almost complete reduction in the resting
      density of An. culicifacies and An. stephensi, the two major malaria vectors and
      also in the reduction of malaria cases in ZeroFly camps as compared to control
      camps. The ZeroFly plastic sheeting was found to be safe for human. Barring some
      complaints of skin irritation and itching, which were temporary in nature, no
      adverse health effects were reported by the users. The community acceptance was
      high. CONCLUSION: Results of the present study revealed that ZeroFly(r) plastic
      sheeting is highly effective in reducing the indoor resting density of
      mosquitoes, man -vector contact and malaria incidences in labour populations
      living in temporary shelters.

PMID- 21946713
TI  - Habitat heterogeneity and prey selection of Aplocheilus panchax: an indigenous
      larvivorous  fish.
AB  - OBJECTIVE: The ability of the native larvivorous fish Aplocheilus panchax
      (Hamilton, 1822) (Cyprinodontiformes: Aplocheilidae) as predator of mosquito
      larvae was assessed under laboratory conditions using multiple prey and habitat
      conditions. METHODS: The consumption of larvae of the mosquito Culex
      quinquefasciatus Say 1823 (Diptera: Culicidae) by A. panchax was evaluated in the
      presence of tubificid worms and chironomid larvae under complex and simple
      habitat conditions. The number of mosquito larvae consumed in comparison to other
      prey types was noted and an index of prey selectivity was used to evaluate the
      preference for mosquito larvae. RESULTS: Aphlocheilus panchax consumed 53 to 65
      mosquito larvae in a three hour feeding bout contrast to 29- 38 tubificid worms
      and 43-62 chironomid larvae depending on the habitat conditions. The prey
      consumption differed significantly between the habitats and the prey type. The
      index of prey selectivity was positive for Cx. quinquefasciatus larvae over other
      alternative prey in all the habitat conditions. CONCLUSION: It is apparent from
      the study that the larvivorous fish A. panchax can be employed for biological
      regulation of mosquitoes in rice -fields and similar wetlands where the multiple
      prey choices are available under complex habitat conditions. However, field
      studies including other prey species will be required to substantiate this
      finding.

PMID- 21946714
TI  - Does electrocardiography at admission predict outcome in Crimean -Congo
      hemorrhagic fever?
AB  - BACKGROUND & OBJECTIVES: Crimean - Congo hemorrhagic fever is an acute viral
      hemorrhagic fever with considerable mortality. Despite increasing knowledge about
      hemorrhagic fever viruses, the pathogenesis of Crimean -Congo hemorrhagic fever
      and causes of death were not well described. We aimed to evaluate whether there
      were electrocardiographic parameters designating mortality among these patients.
      STUDY DESIGN: This retrospective study was performed among confirmed Crimean 
      Congo hemorrhagic fever cases in Turkey. Electrocardiography was available in 49
      patients within 24 h of hospitalization. All electrocardiograms were evaluated by
      two expert cardiologists according to Minnesota coding system. RESULTS: Among
      patients with available electrocardiograms, there were 31 patients who survived,
      and 18 patients who died of Crimean - Congo hemorrhagic fever. Both groups were
      similar in terms of age, sex, body temperature, heart rate, and blood parameters.
      T-wave changes and bundle branch block were more frequently encountered among
      those who died. Presence of T-wave negativity or bundle branch block in this
      cohort of patients with Crimean -Congo hemorrhagic fever predicted death with a
      sensitivity of 72.7%, specificity of 92.6%, positive predictive value of 88.9%,
      negative predictive value of 80.6%. CONCLUSIONS: We think within the light of our
      findings that simple electrocardiography at admission may help risk
      stratification among Crimean-Congo hemorrhagic fever cases.

PMID- 21946715
TI  - HIV and malaria co-infection in Mumbai, western India.
AB  - BACKGROUND & OBJECTIVES: Conflicting reports exist regarding the HIV-1 infection
      on the risk of malaria. A transient almost one-log elevation in HIV viral load
      occurs during febrile malaria episodes. We prospectively studied malaria patients
      for HIV infection from Mumbai. METHODS: A total of 171 malaria patients and
      28,749 normal voluntary blood donors were studied for their HIV status. Diagnosis
      of malaria was done by microscopical examination of blood. HIV screening was done
      by detection of HIV-1 & 2 antibodies by micro well ELISA using Enzaids & J Mitra
      kits followed by confirmation using western blot (Innogenetics, Belgium)
      analysis. RESULTS: Out of 171 malaria patients 13 (7.6%; Odds ratio= 4.45; p
      <0.0001) and 521 blood bank donors were found to be HIV reactive. Among 13 HIV
      reactive patients, eight patients were Elisa borderline reactive and western blot
      positive (p24), which may be due to cross-reactive antibodies. Five of 13 malaria
      patients found to be HIV-1 positive by ELISA and by western blot confirming HIV
      and malaria co-infection. CONCLUSION: Our findings suggest that HIV-1 and malaria
      co-infection can't be ruled out in malaria endemic countries like India.

PMID- 21946716
TI  - Species composition of Phlebotomine sandflies (Diptera: Psychodidae) in Nikshahr
      county, south -eastern Iran.
AB  - BACKGROUND & OBJECTIVES: Sandflies are reported as the vectors of different kinds
      of leishmaniasis to human. There are foci of the disease in Iran. The aim of this
      study was to determine the fauna and species composition of sandflies to find the
      probable vectors of leishmaniasis in Nikshahr county, south-east of Iran, where
      cutaneous leishmaniasis is endemic. METHODS: Sandflies were collected by sticky
      paper traps from 20 collection stations located in plain and mountainous area of
      Nikshahr county. The sex ratio and relative abundance of different species were
      also determined. RESULTS: A total of 11,455 sandflies revealed 23 species
      collected and identified. Phlebotomus alexandri, P. sergenti, P. papatasi, P.
      salehi, and P. keshishiani were the most important vector species found in this
      study. INTERPRETATION & CONCLUSION: During this survey 13 species are identified
      for the first time from Nikshahr county-P. bergeroti, P. eleanorae, P.
      keshishiani, P. halepensis, S. hodgsoni, S. christophersi, S. mervynae, S.
      dentata, S. dreyfussi, S. iranica, S. africana, S. grekovi and S. palestinensis,
      while P. keshishiani is an important vector of visceral leishmaniasis in south of
      Iran. These data demonstrate five vectors of leishmaniasis are active in the
      study area.

PMID- 21946717
TI  - A bibliometric analysis of malaria research in India during 1998-2009.
AB  - OBJECTIVE: This study analyses the research output of India in malaria research
      in national and global context, as reflected in its publications output during
      1998-2009. METHODS: SCOPUS Citation database has been used to retrieve the
      publication data, which has been further analysed on several parameters including
      its growth, rank and global publications share, citation impact, overall share of
      international collaborative papers and share of major collaborative partners and
      patterns of research communication in most productive journals. The publications
      output, impact and collaborative publication share of India is also compared with
      South Africa, Brazil and China. RESULTS: Indian scientists together have
      published 2786 papers in malaria research during 1998-2009 and registered an
      average citation per paper of 3.49. The country ranks 4th among the top 20 most
      productive countries in malaria research with its global publications share of
      6.47% during 1998-2009. CONCLUSION: Quantum of Indian research output in malaria
      research is high but its citations per paper is low compared to select developing
      countries, which can be improved by investing more funds in international and
      national collaborative research projects, as well as increasing the participation
      of researchers in such projects.

PMID- 21946718
TI  - Vector abundance and species composition of Anopheles mosquito in Calabar,
      Nigeria.

PMID- 21946719
TI  - Environmental endocrine disruptors and their effects on Biomphalaria glabrata
      oviposition.

PMID- 21946720
TI  - Falciparum malaria complicated with acute pancreatitis: a report of case series.

PMID- 21946721
TI  - Dengue encephalopathy.

PMID- 21946722
TI  - Mass drug administration for elimination of lymphatic filariasis: a discussion.

PMID- 21946723
TI  - Subarachnoid hemorrhage causing cardiopulmonary arrest: resuscitation profiles
      and outcomes.
AB  - Aneurysmal subarachnoid hemorrhage (SAH) is a common cause of cardiopulmonary
      arrest (CPA). The outcomes of SAH patients presenting with CPA are extremely
      poor, and long-term survivors have occasionally been reported, but the
      circumstances under which SAH-CPA patients achieve long-term survival are
      unclear. Neurosurgeons will have to determine whether a SAH-CPA patient is brain
      dead or not more often after enactment of the revised Organ Transplantation Act.
      Prediction of survival length may be important not only to neurosurgeons, but
      also to the transplantation team. A retrospective study was conducted to
      elucidate how often brainstem function was recovered in resuscitated SAH-CPA
      patients and whether the recovery was associated with longer survival. Among 315
      patients with non-traumatic SAH admitted to our institution during 6 years, 35
      (11%) presented with CPA. Ventricular fibrillation (VF) as initial cardiac rhythm
      was rare, observed only in 1 patient. The survival length ranged from 1 to 15
      days (mean 3.5 +/- 0.7 days), and none achieved long-term survival. Return of
      brainstem function, represented by spontaneous respiration and/or reactive
      pupils, was observed in 6 patients (17%), but was only partial and transient.
      Cardiac arrest to return of spontaneous circulation interval tended to be shorter
      in patients with transient recovery of the brainstem function than in those
      without recovery. However, the survival length was not significantly different
      between the two groups. In addition to the 35 SAH-CPA patients, another 44 SAH
      patients lost both brainstem reflexes and spontaneous respiration within 72 hours
      of admission. As a result, 79 (25%) of the 315 SAH patients were considered to
      have sustained fatal, irreversible brain damage. Review of previous experience
      suggests that SAH-CPA patients may survive only if the cause of cardiac arrest is
      VF and not brainstem damage/respiratory arrest. Approximately one-third of
      resuscitated SAH-CPA patients may die within 24 hours of arrival, for whom the
      declaration of brain death may be difficult.

PMID- 21946724
TI  - Long-term outcome of proton beam radiosurgery for arteriovenous malformations
      larger than 30 mm in diameter.
AB  - The effectiveness of proton beam (PB) radiosurgery for large lesions is greater
      than for other treatment modalities. At our institute, PB radiosurgery is used to
      treat arteriovenous malformations (AVMs). We report the outcome of PB
      radiosurgery for AVMs over a period of 15 years, focusing on the efficacy of PB
      radiosurgery combined with embolization for AVMs >=30 mm in diameter. We
      retrospectively analyzed 11 patients with AVMs >=30 mm in diameter who were
      treated with PB radiosurgery between June 1990 and September 2005 at the Proton
      Medical Research Center of the University of Tsukuba. The mean irradiation dose
      was 25.3 gray-equivalent, and the mean duration of clinical follow up was 134.2
      months (median 138 months). Pre-radiosurgical embolization was performed in all
      cases. Complete obliteration was achieved in 9 of the 11 patients. One patient
      experienced post-radiosurgical hemorrhage, and 1 patient experienced radiation
      related aggravation of clinical symptoms due to radiation necrosis. Eight
      patients had excellent outcomes. The multimodal therapy approach of combining pre
      radiosurgical embolization and PB radiosurgery for AVMs yielded a favorable
      outcome for AVMs >=30 mm in diameter. Thus, PB radiosurgery is a viable treatment
      option for AVMs >=30 mm in diameter.

PMID- 21946725
TI  - Preoperative diagnosis of intramedullary spinal schwannomas.
AB  - Intramedullary spinal schwannomas are rare benign spinal cord tumors and are
      easily misdiagnosed because of the imaging characteristics shared with
      intramedullary glioma. Correct preoperative definitive diagnosis is essential for
      treatment and prognosis. To improve the preoperative diagnostic strategy,
      clinical and imaging data of seven patients with intramedullary spinal schwannoma
      (6 men, mean age 44 years, mean duration of illness 4.2 years) treated in our
      department between 2003 and 2010 were collected and retrospectively evaluated.
      The cervical cord was affected in five patients, followed by the thoracic cord in
      two. All seven cases were misdiagnosed as intramedullary glioma based on the
      imaging characteristics. Comparison of the clinical features of these 7 patients
      with those of patients with intramedullary tumors (173 ependymomas and 70
      astrocytomas) admitted during the same period revealed significant differences in
      somatic pain and root pain as the initial symptoms between intramedullary spinal
      schwannomas and ependymomas (p = 0.005) and between intramedullary spinal
      schwannomas and astrocytomas (p = 0.019), but not between ependymomas and
      astrocytomas (p = 0.175). Root or somatic pain as an initial symptom is important
      for the preoperative diagnosis of intramedullary spinal schwannoma, especially if
      the imaging characteristics are not entirely specific.

PMID- 21946726
TI  - Programmable shunt valves: in vitro assessment of safety of the magnetic field
      generated by a portable game machine.
AB  - Cerebrospinal fluid (CSF) shunts are frequently used to treat hydrocephalus. The
      use of a programmable shunt valve allows physicians to easily change the opening
      pressure. Since patients with adjustable CSF shunt valves may use portable game
      machines, the permanent magnets in these machines may alter the shunt valve
      programmed settings or permanently damage the device. This study investigated the
      risk of unintentional valve adjustment associated with the use of game machines
      in patients with programmable CSF shunt valves. Four adjustable valves from 4
      different manufacturers, Sophysa Polaris model SPV (Polaris valve), Miethke
      proGAV (proGAV), Codman Hakim programmable valve (CHPV), and Strata II small
      valve (Strata valve), were evaluated. Magnetic field interactions were determined
      using the portable game machine, Nintendo DS Lite (DS). The maximum distance
      between the valve and the DS that affected the valve pressure setting was
      measured by x-ray cinematography. The Polaris valve and proGAV were immune to
      unintentional reprogramming by the DS. However, the settings of the CHPV and
      Strata valves were randomly altered by the DS. Patients with an implanted shunt
      valve should be made aware of the risks posed by the magnetic fields associated
      with portable game machines and commonly used home electronics.

PMID- 21946727
TI  - Intrinsic arteriovenous malformation embedded in the trigeminal nerve of a
      patient with trigeminal neuralgia.
AB  - A 66-year-old man presented with typical right trigeminal neuralgia. Neuroimaging
      showed a small arteriovenous malformation (AVM) in the right cerebellopontine
      angle. Suboccipital craniotomy verified that the AVM was almost completely
      embedded in the root entry zone of the trigeminal nerve and the nerve axis was
      tilted infero-posteriorly. The patient obtained complete pain relief without
      sequelae after surgery by transposition of the superior cerebellar artery and
      correction of the tilted nerve axis. The nidus of the unresected AVM was
      obliterated by gamma knife radiosurgery.

PMID- 21946728
TI  - Dural arteriovenous fistula between inferolateral trunk of the internal carotid
      artery and superficial sylvian vein.
AB  - A 40-year-old Brazilian man presented with headache followed by consciousness
      disturbance. Computed tomography showed subarachnoid hemorrhage with right
      frontal hematoma. Angiography revealed a dural arteriovenous fistula (dAVF) fed
      by the inferolateral trunk of the internal carotid artery and draining into the
      superficial sylvian vein with varix formation. The shunting point was directly
      obliterated through a pterional approach. Postoperative angiography showed
      complete disappearance of the fistula. A ventriculoperitoneal shunt was needed
      for normal pressure hydrocephalus during his hospitalization. The modified Rankin
      scale at discharge was grade 2 with mild cognitive dysfunction. This case of dAVF
      may represent congenital dAVF.

PMID- 21946729
TI  - Ruptured anterior cerebral artery aneurysm at the origin of the accessory middle
      cerebral artery.
AB  - A 36-year-old female patient was admitted to our hospital with a rare case of
      aneurysm at the origin of the accessory middle cerebral artery (MCA) manifesting
      as severe headache and vomiting. Neurological examination did not detect any
      abnormalities or consciousness disturbance. Computed tomography demonstrated
      diffuse subarachnoid hemorrhage. Magnetic resonance angiography showed an
      aneurysm in the horizontal portion of the left anterior cerebral artery (A(1)).
      Digital subtraction angiography and three-dimensional digital subtraction
      angiography demonstrated a saccular aneurysm originating at the junction of the
      left A(1) and accessory MCA. Another accessory MCA originated at the proximal
      portion of the left A(2) without an aneurysm. Two accessory MCAs were found on
      the left. Neck clipping was performed via a left pterional approach. One month
      after admission, she was discharged without neurological deficits.

PMID- 21946730
TI  - Dissection aneurysm of the radiculomedullary branch of the artery of Adamkiewicz
      with subarachnoid hemorrhage.
AB  - A 60-year-old female presented with sudden onset of severe headache and back
      pain, followed by nausea. The initial head computed tomography (CT) scan revealed
      posterior fossa subarachnoid hemorrhage (SAH). Spinal T(2)-weighted magnetic
      resonance imaging demonstrated SAH, and a homogeneous and slightly low signal
      intensity mass at T11. Spinal angiography in the early arterial phase revealed a
      small pearl and string-like aneurysm of the proximal radiculomedullary artery on
      the left side at the T12 level. Forty days after the onset of SAH, CT angiography
      demonstrated complete occlusion of the dissecting aneurysm and the preserved
      anterior spinal artery. The present case of ruptured dissecting aneurysm of the
      radiculomedullary branch of the artery of Adamkiewicz with SAH underwent
      subsequent spontaneous occlusion, indicating that the wait-and-see strategy may
      be justified and will provide adequate treatment.

PMID- 21946731
TI  - "Kissing" aneurysms of the internal carotid artery treated by coil embolization.
AB  - A 62-year-old female complaining of sudden severe headache was referred to our
      stroke center in consultation. Computed tomography showed diffuse spread of thick
      subarachnoid hemorrhage to the basal cistern and both sylvian fissures, and
      digital subtraction angiography showed kissing aneurysms arising in the left
      lateral and occipital directions in the C(1) portion of the internal carotid
      artery (ICA). The anterior choroidal artery was situated between the two
      aneurysms, and another small branch originating from the dome of the distal
      aneurysm was confirmed as a duplicated middle cerebral artery (MCA). Endovascular
      treatment was successfully performed to spare the two vessels involved. This case
      of kissing aneurysms and ICA-duplicated MCA is very rare, and presents
      difficulties for both surgical and endovascular treatments.

PMID- 21946732
TI  - Coil embolization for a ruptured posterior cerebral artery aneurysm with
      vertebrobasilar dolichoectasia.
AB  - A 74-year-old man suffered sudden loss of consciousness at home. Computed
      tomography revealed severe subarachnoid hemorrhage and an unusual posterior
      cerebral artery (PCA) aneurysm with vertebrobasilar dolichoectasia (VBD). The
      aneurysm was located in the right hypothalamus. VBD associated with a distal
      lesion makes endovascular treatment difficult because of the elongation and
      tortuosity of the access route. However, endovascular coil embolization was
      successful for the present ruptured PCA aneurysm with VBD.

PMID- 21946733
TI  - Middle cerebral-anterior cerebral-radial artery interposition graft bypass for
      proximal anterior cerebral artery aneurysm.
AB  - A 74-year-old man underwent pterional craniotomy to treat a left proximal
      anterior cerebral artery (ACA) aneurysm. The orifice of the aneurysm was located
      at the origin of the proximal segment of the ACA, and the right A(1) segment of
      ACA was hypoplastic. After failed attempts at neck plasty with fenestrated clips,
      trapping and bypass were performed. Superficial temporal to left frontopolar
      artery bypass was performed to secure minimal blood supply. The radial artery
      (RA) was then harvested, and middle cerebral artery (MCA) to A(1) segment of the
      ACA bypass was performed using the RA interposition graft. Trapping of the
      aneurysm was successfully achieved without ischemic event. Intracranial
      intracranial bypass has been employed in the treatment of complex cerebral
      aneurysm in an increasing number of selected patients. The present case shows
      that MCA-ACA-RA interposition graft bypass is an effective procedure to provide
      blood supply to the ACA territory if a proximal A(1) lesion requires trapping
      with incompetent contralateral A(1).

PMID- 21946734
TI  - Development of cervical subarachnoid hematoma following coronal artery stenting
      for angina pectoris.
AB  - A 78-year-old man presented with a rare massive subarachnoid hematoma (SAH) in
      the cervical spine after coronary stenting for angina pectoris. Chest pain and
      electrocardiographic changes were resolved after administration of coronary
      dilator and coronary stenting, but shoulder pain persisted. At 6 hours after
      stenting, left hemiparesis was found with deteriorated shoulder pain. Computed
      tomography and magnetic resonance imaging revealed massive SAH in the cervical
      spine. Emergent hematoma evacuation with laminoplasty was performed because of
      rapid progression of the hemiparesis and pain. The hemiparesis was ameliorated
      after surgery. Spinal hematoma should be considered in the differential diagnosis
      in patients receiving anti-platelet or anti-coagulant drugs with rapid
      progression of pain.

PMID- 21946735
TI  - Granulomatous amoebic encephalitis caused by Balamuthia mandrillaris.
AB  - A 51-year-old immunocompetent Japanese woman presented with a rare case of
      granulomatous amoebic encephalitis (GAE) caused by Balamuthia mandrillaris. She
      was brought to our hospital with epilepsy. Magnetic resonance imaging of the
      brain revealed a homogeneously enhanced solitary mass in the left frontal lobe.
      Histological diagnosis was made by a biopsy, which suggested lymphomatoid
      granulomatosis. After that, her neurological condition got worse. New masses were
      found and had spread across the whole brain. She died 2 months later of cerebral
      hernia. Autopsy revealed that the patient had GAE caused by Balamuthia
      mandrillaris. GAE is usually fatal, and is difficult to diagnose except at
      autopsy. Therefore, awareness of this disease is important, and earlier diagnosis
      and the development of a better therapeutic strategy will improve clinical
      outcome.

PMID- 21946736
TI  - Dural cyst at the foramen magnum.
AB  - A 69-year-old male presented with a rare dural cyst manifesting as numbness and
      pain in the limbs. Magnetic resonance imaging revealed a mass anterior to the
      medulla oblongata appearing as low intensity on T(1)-weighted and high intensity
      on T(2)-weighted imaging, with no enhancement. A cystic lesion ventral to the
      medulla oblongata was removed via the lateral suboccipital transcondylar
      approach. Histological examination showed the wall of the cyst consisted of
      fibrous connective tissue with a dense zone and a loose zone, similar to the
      structure found in the dura mater. The lesion was diagnosed as dural cyst. Dural
      cysts can be defined as cyst with the wall consisting of dura mater-like fibrous
      tissue, and attached to the dura mater. The origin of the present dural cyst was
      considered to be congenital.

PMID- 21946738
TI  - The impact of alcohol-related presentations in the emergency department and the
      wider policy debate.

PMID- 21946737
TI  - Cervical unilateral open-door laminoplasty with titanium miniplates through newly
      designed hydroxyapatite spacers.
AB  - A newly designed hydroxyapatite (HA) spacer for cervical laminoplasty is provided
      with a hole through which the titanium miniplate is passed. A new method of
      unilateral open-door laminoplasty with titanium miniscrew and miniplate through
      this HA spacer is described. Twenty-two patients with cervical stenotic disorders
      were treated by this procedure. Only the predominantly affected side of the
      laminae is exposed. The supraspinous and interspinous ligaments and the deep
      muscle layer in the contralateral side are left intact. A 4-mm wide gutter near
      the intervertebral joint is made and contralateral hinges are made under the deep
      muscle layer with minimum detachment of these muscles. The opened lamina is fixed
      with the titanium miniplate passed through the hole in the newly designed HA
      spacer. Mean operative time for the 22 operations was 193.5 minutes. Mean
      enlargement of the minimum spinal canal diameter was 50.9%. Neurological outcomes
      after 3 months were evaluated according to the Japanese Orthopaedic Association
      (JOA) scoring. Mean recovery rate of JOA score by Hirabayashi's method was 49.5%.
      Only 2 patients reported postoperative axial neck pain. Our method for unilateral
      open-door laminoplasty provides adequate decompression and tight fixation of
      laminae, and is less invasive to the posterior supporting elements of cervical
      spine.

PMID- 21946739
TI  - Off-label use of quetiapine in New Zealand--a cause for concern?

PMID- 21946740
TI  - How do intoxicated patients impact staff in the emergency department? An
      exploratory study.
AB  - AIM: To investigate staff perceptions of the burden of alcohol-related
      presentations on emergency departments (ED) in New Zealand and the impact on
      staff of alcohol-related ED presentations. METHODS: A survey of Wellington
      Regional Hospital ED staff was conducted using a written questionnaire to measure
      the impact of alcohol on: staff assault rates, perceived workload, quality of
      care, and staff mood. In addition, semi-structured interviews were conducted with
      six ED staff to further explore impacts of alcohol on ED, analysed using thematic
      analysis. RESULTS: Forty-seven staff members responded to the questionnaire.
      Assault rates from alcohol-affected patients were high, particularly amongst
      nurses. These were mostly verbal assaults. Staff mood was negatively affected and
      perceptions of workload increased by alcohol-related presentations. Views on
      whether quality of care of intoxicated patients was affected were mixed although
      most reported a negative impact on other patients. Interviews confirmed the
      survey results, confirming the negative impacts of alcohol-related presentations
      on staff and on the treatment of both intoxicated and non-intoxicated patients.
      CONCLUSION: This small exploratory study found that alcohol-related presentations
      have a negative impact on ED staff workload and safety, and may compromise
      treatment of all patients. More research is needed to corroborate these findings
      and to investigate policies to reduce the impacts of alcohol-related
      presentations in the ED.

PMID- 21946741
TI  - Off-label use of atypical antipsychotic medications in Canterbury, New Zealand.
AB  - AIM: To estimate the frequency and characteristics of "off-label" use of atypical
      antipsychotic medications (AAPs) by psychiatrists in Canterbury, New Zealand.
      METHODS: Data on "off-label" prescribing of AAPs including the choice of
      medication, frequency of prescribing, and the indications for its use was
      collected using a postal survey of psychiatrists registered with the NZ Medical
      Council in the Canterbury region. RESULTS: 48 psychiatrists (71%) completed the
      survey. Forty-six (96%) prescribed AAPs "off-label". By far the most common agent
      was quetiapine (94%). Twenty-eight respondents (58%) prescribed "off-label" at
      least once a week. The most common reasons for the use of these agents was:
      anxiety (89%), sedation (79%), post-traumatic stress disorder (57%), treatment
      augmentation of another antipsychotic agent (48%) and behavioural and
      psychological symptoms of dementia (33%). CONCLUSION: "Off-label" prescribing,
      particularly of quetiapine is very common in the Canterbury region, despite
      little scientific evidence for this kind of use, increasing evidence of abuse and
      potential for significant side-effects.

PMID- 21946742
TI  - Five-year follow-up of an acute psychiatric admission cohort in Auckland, New
      Zealand.
AB  - AIM: This paper describes a follow-up of acute psychiatric hospital contact in
      Auckland, New Zealand for an admission cohort in the 5-years past an index
      admission (published in the NZMJ in 2005). METHODS: A 5-year follow-up study of
      hospital psychiatric service utilisation by 924 patients admitted (index
      admission) in Auckland during 2000. Hospital admissions within New Zealand for
      this population were extracted from electronic records. Relevant demographic
      information (gender, age and ethnicity) and clinical data (primary diagnosis at
      index admission and admission history) were included for each person. Descriptive
      analysis of inpatient data and negative binomial regression models were
      conducted. RESULTS: Of 924 patients, 38.5% had no readmissions anywhere in New
      Zealand in the 5-years following index discharge. 41.0% were readmitted within 12
      months and 61.4% were readmitted within 5 years of index discharge. Only 5.6%
      experienced an admission every year for the 5-years post index admission.
      Readmission was least likely for those with index discharge diagnosis of
      depression. A history of admissions prior to index admission and Maori ethnicity
      were characteristics associated with higher numbers of readmission. Those who
      were younger, or a diagnosis of schizophrenia/schizoaffective disorder or
      previous admissions tended to have longer total length of stay over the 5-years.
      CONCLUSIONS: More than a third of patients had no further hospital contact and
      the two factors associated with readmission were a history of previous admissions
      and Maori ethnicity. Reliable community-based data needs to be a priority to
      enable exploration of community service utilisation and impact of service
      alternatives to hospital for acute care.

PMID- 21946743
TI  - Quetiapine for the treatment of behavioural and psychological symptoms of
      dementia (BPSD): a meta-analysis of randomised placebo-controlled trials.
AB  - AIM: This meta-analysis is aimed to determine the efficacy of quetiapine for the
      treatment of behavioural and psychological symptoms of dementia (BPSD). METHOD:
      Our electronic search included MEDLINE (1950-2009), Cochrane Central Register of
      Controlled Trials and PsychINFO. We also did a hand search of the International
      Psychogeriatric Association poster presentations and checked the National trial
      registry data bases from USA, UK, RSA, Holland, Australia and New Zealand. We
      included double-blinded randomised placebo-controlled trials studies that
      measured BPSD with the Neuropsychiatric Inventory (NPI). The Clinical Global
      Impression of Change scale (CGI-C) was our secondary outcome. RESULTS: Six sets
      of data were included in this meta-analysis. Patients receiving quetiapine
      improved when compared to placebo with a weighted mean difference of - 3.05 (95%
      CI: -6.10, -0.01) and -0.31 (95% CI: -0.54, -0.08) respectively on the NPI score
      and CGI-C score. CONCLUSION: This meta-analysis found that quetiapine is
      statistically more efficacious than placebo in the treatment of BPSD as measured
      by the NPI and CGI-C. However, improvement is of a small magnitude and observable
      clinical significance is questionable.

PMID- 21946744
TI  - Narcolepsy in New Zealand: pathway to diagnosis and effect on quality of life.
AB  - AIMS: There has been no attempt to survey New Zealanders with narcolepsy to
      determine their pathway to diagnosis, symptoms, treatment, or quality of life. We
      therefore aimed to develop a comprehensive questionnaire, and compare responses
      on measures of daytime sleepiness and quality of life between individuals with
      narcolepsy and the general New Zealand population. METHODS: A questionnaire was
      developed encompassing descriptive information, daytime sleepiness and sleep
      habits, general health and wellbeing, diagnosis and treatment of narcolepsy,
      symptoms, and quality of life. Ninety-two individuals were identified through
      medical specialists and a local support group. RESULTS: Complete responses were
      obtained from 54 individuals (63% female, mean age 54.7 +/- 18.3 years). The mean
      Epworth Sleepiness Scale score was 16.4 +/- 5.4 (/24). Symptoms first appeared at
      20.7 +/- 9.7 years of age on average, although diagnosis did not take place until
      33.4 +/- 13.8 years of age. Individuals with narcolepsy reported substantially
      lower health-related quality of life than the general New Zealand population.
      Less than half of those diagnosed with narcolepsy had undergone an objective
      evaluation including a sleep study. CONCLUSIONS: New Zealanders with narcolepsy
      suffer from an excessive level of daytime sleepiness, and have significantly
      poorer health-related quality of life than the general population. There are a
      number of inconsistencies between the diagnostic pathway in New Zealand and best
      practice guidelines for diagnosis and treatment.

PMID- 21946746
TI  - Controlled intoxication: the self-monitoring of excessive alcohol use within a
      New Zealand tertiary student sample.
AB  - AIMS: Drawn from a study aimed at exploring students' drinking behaviour and
      attitudes, this article focuses upon findings that revealed how heavy-drinking
      students monitored and managed their experiences of alcohol intoxication.
      METHODS: 819 students residing within three university student residences were
      invited to participate in three phases of data collection. Utilising a
      combination of qualitative and quantitative research methods, a total of 15 focus
      group interviews and 18 indepth interviews were undertaken, and 501 students
      (61%) completed a written survey questionnaire. RESULTS: Sixty percent of
      students agreed with the statement "I usually know beforehand if I am going to
      get drunk". One-half of male drinkers and one-third of female drinkers reported
      they were intoxicated on a weekly basis. When drinking to intoxication, the
      majority of students monitored a range of drinking effects (a total of 14 were
      identified) which they considered were signals for the need to either slow down
      or stop drinking. CONCLUSIONS: The majority of drinkers in this study who consume
      alcohol with the intention of getting intoxicated, typically drink to a
      predetermined level of intoxication, and maintain that level by monitoring a
      range of drinking effects--this behaviour has been termed controlled
      intoxication. Future harm-minimisation strategies could be developed that
      encourage heavy-drinkers to adopt 'safer' drinking-effect signals as indicators
      to slow down or stop drinking.

PMID- 21946745
TI  - Patterns of prescription drug misuse presenting to provincial drug clinics.
AB  - AIM: To survey new patients, presenting to three drug clinics, on the patterns,
      usage and costs of prescription pharmaceuticals. METHOD: Consecutive patients
      seen by the medical staff for assessment had a 7-day history recorded for
      prescription drug (PD) usage, and the associated costs of these from street
      sources. RESULTS: There were 37 patients (26 males) with a mean age of 34 years
      (21-51). Ten reported using only intravenous (IV) morphine, at a median dose of
      105 mg/day (40-600), at a mean cost of 56 cents/mg. Another 12 reported methadone
      as their sole opioid at a median dose of 50 mg/day (27-70), at a mean cost of 81
      cents/mg. A further 11 used a mixture of opioids, predominantly morphine and
      methadone but also dihydrocodeine (3), oxycodone (1), tramadol (1) and codeine
      (2). Seventeen reported also using hypnosedatives, but did not report high doses
      of these. The overall weekly expenditure on PDs was $367/week (0-2100).
      CONCLUSIONS: Morphine and methadone remain the predominant street opioid PDs in
      this region. Street prices have reduced, perhaps reflecting greater drug
      availability in accordance with increased national prescribing of opioids. There
      is continuing diversion of PDs to the street which is an ongoing Public Health
      issue requiring coordinated responses, including improved prescribing training,
      pain guidelines, drug clinic policy and actions by Medsafe, Police and regulatory
      bodies to contain this problem.

PMID- 21946747
TI  - Alcohol's harm to others: self-reports from a representative sample of New
      Zealanders.
AB  - AIM: There is a lack of research, internationally and in New Zealand, on the
      harms experienced as a result of drinking by others. Such effects have often been
      neglected in policy development and in estimates of the economic burden
      associated with alcohol consumption. This study describes the broad range of
      harms reported by New Zealanders due to the drinking of someone else. METHOD: A
      representative national survey was conducted using Computer Assisted Telephone
      Interviewing with New Zealanders aged 12 to 80 years (N=3068) in 2008/2009
      (response rate - 64%). Harms experienced due to the drinking of others were
      reported along with demographic variables. RESULTS: One in four respondents
      indicated that they had at least one heavy drinker in their life. Most of these
      respondents indicated they had experienced a range of harms because of this
      person's drinking. Further, 17% of respondents with children reported that their
      children experienced harm because of the drinking of someone else. Seventy-one
      percent of those sampled reported experiencing at least one harm because of the
      drinking of a stranger. CONCLUSION: A large proportion of New Zealanders report
      the experience of physical, social, economic, and psychological harms because of
      the drinking of others. These harms should be considered in the discussion of
      alcohol policy.

PMID- 21946748
TI  - The benefits and harms of alcohol use in New Zealand: what politicians might
      consider.
AB  - The New Zealand Government is currently considering ways to reduce alcohol
      related harm, following on from a detailed report by the Law Commission. To
      inform discussions we briefly summarise the benefits and harms of alcohol use in
      this country. The most substantive benefits to society are probably pleasure to
      users and economic benefits (largely to industry). The most substantive harms are
      probably those to mental and physical health, harm to society (e.g. from crime)
      and adverse net economic impacts. Overall the picture is suggestive that New
      Zealand society would be likely to achieve a large net benefit from reducing
      heavy and binge drinking, and shifting alcohol consumption towards a pattern of
      smaller amounts. The substantial harm to non-users is a key argument for
      democratic governments to use regulations and taxes to minimise harm from
      alcohol.

PMID- 21946749
TI  - Medical image. Stenosis of bilateral main bronchus secondary to lung cancer.

PMID- 21946750
TI  - Medical image. Bilateral diffuse cystic, cavitary lung metastasis of
      adenocarcinoma.

PMID- 21946751
TI  - Lifetime cardiovascular risk.

PMID- 21946752
TI  - Important questions about healthcare expenditure and the allocation of resources
      in the last year of life.

PMID- 21946753
TI  - Use of Asthma Control Test (ACT) affects New Zealand primary care doctors'
      perception of asthma control.

PMID- 21946754
TI  - Advocacy for general practice.

PMID- 21946755
TI  - Can many anterior cruciate ligament (ACL) ruptures heal without surgery?

PMID- 21946756
TI  - Revenge of the ACL.

PMID- 21946757
TI  - Consequences of a flawed epidemiological approach to air quality regulation.

PMID- 21946758
TI  - Nicotine replacement therapy in grocery stores; but wait, there's more.

PMID- 21946759
TI  - On the mechanism of enhanced oxygen reduction reaction in nitrogen-doped graphene
      nanoribbons.
AB  - Nitrogen (N)-doped carbon materials were shown in recent studies to have
      promising catalytic activity for oxygen reduction reaction (ORR) as a metal-free
      alternative to platinum, but the underlying molecular mechanism or even the
      active sites for high catalytic efficiency are still missing or controversial
      both experimentally and theoretically. We report here the results of periodic
      density functional theory (DFT) calculations about the ORR at the edge of a
      graphene nanoribbon (GNR). The edge structure and doped-N near the edge are shown
      to enhance the oxygen adsorption, the first electron transfer, and also the
      selectivity toward the four-electron, rather than the two-electron, reduction
      pathway. We find that the outermost graphitic nitrogen site in particular gives
      the most desirable characteristics for improved ORR activity, and hence the
      active site. However, the latter graphitic nitrogen becomes pyridinic-like in the
      next electron and proton transfer reaction via the ring-opening of a cyclic C-N
      bond. This inter-conversion between the graphitic and pyridinic sites within a
      catalytic cycle may reconcile the controversy whether the pyridinic, graphitic,
      or both nitrogens are active sites.

PMID- 21946760
TI  - Granulomatous reaction after injection of a new resorbable filler Novabel.
AB  - A new resorbable filler, Novabel, became commercially available in January 2010
      in France. A 52-year-old general practitioner injected 0.1 cm3 of a 1 cm3
      alginate solution (Novabel) into the deep dermis of her left arm to test it
      before using it on her patients. Ten days later, she observed a small pink nodule
      at the injection site forming secondary a bluish papule. A biopsy was performed 2
      months after the injection. Histopathology showed a granulomatous reaction
      involving the deep dermis and the subcutaneous fat. The inflammatory reaction
      surrounded a nonpolarizing exogenous material consisting of slightly bluish
      deposits of variable size and shape, some of which were well delineated, others
      with a blurred or spiky perimeter, frequently showing retraction in a clear
      vacuole. The papule regressed, resolving completely 5 months after the injection.
      Novabel is a totally new type of aesthetic injectable resorbable filler
      consisting of a purified polysaccharide, alginate, which is extracted from
      crusted brown algae. No side effects have been reported to date and we describe
      here a first granulomatous reaction after filler injection which has a
      distinctive appearance in keeping with the histopathological findings.

PMID- 21946761
TI  - Cutaneous manifestations of B-cell chronic lymphocytic leukemia associated with
      Borrelia burgdorferi infection showing a marginal zone B-cell lymphoma-like
      infiltrate.
AB  - We report on a 69-year-old female patient with specific cutaneous manifestations
      of B-cell chronic lymphocytic leukemia that arose at the site of erythema
      chronicum migrans due to Borrelia burgdorferi infection. Histological examination
      revealed the presence of dense infiltrates of small hyperchromatic lymphocytes
      admixed with clusters of plasma cells. Immunohistology showed a CD5+/CD20+
      phenotype of the lymphocytes and monoclonal expression of kappa immunoglobulin
      light chain by the plasma cells. Presence of Borrelia DNA was confirmed by
      polymerase chain reaction studies. The unusual histopathological and phenotypic
      findings described in this case of cutaneous manifestations of B-cell chronic
      lymphocytic leukemia associated with Borrelia burgdorferi infection may lead to
      the misdiagnosis of cutaneous marginal zone B-cell lymphoma.

PMID- 21946762
TI  - Primary cutaneous, composite, Epstein-Barr virus-associated, diffuse large B-cell
      lymphoma and peripheral T-cell lymphoma.
AB  - T-cell lymphomas have a broad spectrum of cutaneous involvement. Several subtypes
      of T-cell lymphomas are associated with Epstein-Barr virus (EBV)-driven
      lymphoproliferative processes. We present a case of a composite, primary,
      cutaneous, EBV-associated, diffuse, large B-cell lymphoma and mature T-cell
      lymphoma occurring in a patient with Klinefelter karyotype (47, XXY). The patient
      had a characteristic clinical course of a systemic mature T-cell lymphoma before
      the presentation of the composite, primary, EBV-associated, diffuse, large B-cell
      lymphoma. Although similar cases have been described in extracutaneous locations,
      we believe that this is the first description with a primary cutaneous
      presentation.

PMID- 21946763
TI  - Spontaneous cutaneous cholesterol crystal embolism with focal clinical
      symptomatology: report of a case in an unusual location with secondary
      histological changes reminiscent of atypical decubital fibroplasia.
AB  - Cholesterol crystal embolization (CCE) is one of the many complications of
      atherosclerosis. CCE is usually an iatrogenic event occurring either after
      vascular surgery, usually aortic surgery, or invasive angiographic investigations
      or in the course of anticoagulant or thrombolytic therapy. More rarely, it occurs
      after trauma or even in the absence of any inciting cause. CCE may manifest with
      single or multiorgan involvement. Skin involvement is usually seen in the context
      of a systemic disease, especially affecting the lower extremities and lower
      trunk. We report on a rare case of isolated spontaneous focal cutaneous
      involvement of the upper limb, with peculiar mesenchymal and reactive
      histological changes. A 65-year-old man with a clinical history of
      atherosclerosis was admitted complaining of a nonhealing painful skin ulceration
      on his left elbow for 5-month duration. A skin biopsy was taken, and
      histopathological examination documented an intrarteriolar cholesterol embolus in
      the dermis along with a peculiar adjacent bizarre fibroblastic reaction, of the
      type usually seen in atypical decubital fibroplasia of debilitated patients. The
      ulceration was surgically excised, and the wound was sutured and repaired. At 18
      month follow-up, the patient has no evidence of local disease.

PMID- 21946764
TI  - Dendritic cell neurofibroma sine pseudorosettes: report of a case with a
      granulomatous appearance.
AB  - An unusual variant of dendritic cell neurofibroma is reported. In contrast to
      previous cases, the formation of pseudorosettes was lacking. The tumor was
      located on the anterior aspect of the thigh in a previously healthy 71-year-old
      woman with no evidence of neurofibromatosis. The tumor was composed of type-1 and
      type-2 cells, which were immunoreactive for S-100 protein and CD57. The
      granulomatous appearance was due to the zonal accumulation of CD34-positive
      dendritic cells and type-1 cells in a serpiginous fashion surrounding large areas
      with lesser cellularity featuring type-2 cells with scattered type-1 cells
      arranged in a haphazard fashion. Intralesional small neurites positive for
      neurofilament and perilesional perineural cells positive for epithelial membrane
      antigen were documented immunohistochemically.

PMID- 21946765
TI  - Local lymph node micrometastasis in a patient with negative sentinel lymph node
      biopsies after lymphatic mapping with wide local excision of primary melanoma on
      the head/neck area.
AB  - Sentinel lymph node biopsy is widely accepted as a staging procedure for patients
      with cutaneous melanoma who are at risk for metastases. The complex lymphatic
      drainage pattern on the head and neck makes sentinel lymph node mapping more
      challenging compared with other sites. Here, we report a patient who underwent
      reexcision of the primary tumor site with lymphatic mapping on the right
      posterior auricular area. Four sentinel nodes were negative for melanoma
      metastasis; however, step sectioning of the wide local excision of the primary
      tumor site revealed a small lymph node with histopathologic detection of
      micrometastasis. Our findings highlight the importance of a careful
      histopathologic approach that may have prognostic impact on outcome and survival.

PMID- 21946766
TI  - Performance of the bispectral index during electrocautery.
AB  - BACKGROUND: The electroencephalogram contains small electrical signals that are
      vulnerable to contamination from high-frequency noise during electrocautery. The
      bispectral index (BIS) monitor incorporated hardware and software changes to
      eliminate artifacts, thus allowing BIS monitoring even in the presence of
      electrocautery. We evaluated the accuracy of BIS to measure anesthetic effect
      during electrocautery interference. METHODS: Anesthesia was induced and
      maintained with target-controlled infusions of propofol (3 MUg/mL) and
      remifentanil (4 ng/mL). After baseline BIS recordings, "simulated" electrocautery
      interference was induced continuously for 20 minutes. Five minutes after the
      start of electrocautery, propofol infusion was increased to achieve an effect
      site concentration of 6 MUg/mL. Patients remained undisturbed during the study.
      BIS values and signal quality index were recorded continuously. RESULTS: During
      electrocautery, there was a significant decrease in signal quality index (mean
      difference: 16.9; 95% confidence intervals: 15.9-17.9; P<0.001). There was,
      however, no change in BIS value even after a step increase in propofol infusion
      from 3 to 6 MUg/mL (P=0.93). In 22% of the patients there was a paradoxical
      increase in BIS values after doubling of propofol concentration. Following
      cessation of electrocautery, there was a prompt decrease in BIS (P<0.001),
      indicating a lack of response to the change in anesthetic depth during
      electrocautery. CONCLUSIONS: Rejecting and filtering artifacts from
      electrocautery interference reduced the ability of BIS to respond to a change in
      anesthetic depth. BIS values during electrocautery should be interpreted with
      caution.

PMID- 21946767
TI  - Multiparametric optical mapping of the Langendorff-perfused rabbit heart.
AB  - Optical imaging and fluorescent probes have significantly advanced research
      methodology in the field of cardiac electrophysiology in ways that could not have
      been accomplished by other approaches(1). With the use of the calcium- and
      voltage-sensitive dyes, optical mapping allows measurement of transmembrane
      action potentials and calcium transients with high spatial resolution without the
      physical contact with the tissue. This makes measurements of the cardiac
      electrical activity possible under many conditions where the use of electrodes is
      inconvenient or impossible(1). For example, optical recordings provide accurate
      morphological changes of membrane potential during and immediately after
      stimulation and defibrillation, while conventional electrode techniques suffer
      from stimulus-induced artifacts during and after stimuli due to electrode
      polarization(1).  The Langendorff-perfused rabbit heart is one of the most
      studied models of human heart physiology and pathophysiology. Many types of
      arrhythmias observed clinically could be recapitulated in the rabbit heart model.
      It was shown that wave patterns in the rabbit heart during ventricular
      arrhythmias, determined by effective size of the heart and the wavelength of
      reentry, are very similar to that in the human heart(2). It was also shown that
      critical aspects of excitation-contraction (EC) coupling in rabbit myocardium,
      such as the relative contribution of sarcoplasmic reticulum (SR), is very similar
      to human EC coupling(3). Here we present the basic procedures of optical mapping
      experiments in Langendorff-perfused rabbit hearts, including the Langendorff
      perfusion system setup, the optical mapping systems setup, the isolation and
      cannulation of the heart, perfusion and dye-staining of the heart, excitation
      contraction uncoupling, and collection of optical signals. These methods could be
      also applied to the heart from species other than rabbit with adjustments to flow
      rates, optics, solutions, etc. Two optical mapping systems are described. The
      panoramic mapping system is used to map the entire epicardium of the rabbit
      heart(4-7). This system provides a global view of the evolution of reentrant
      circuits during arrhythmogenesis and defibrillation, and has been used to study
      the mechanisms of arrhythmias and antiarrhythmia therapy(8,9). The dual mapping
      system is used to map the action potential (AP) and calcium transient (CaT)
      simultaneously from the same field of view(10-13). This approach has enhanced our
      understanding of the important role of calcium in the electrical alternans and
      the induction of arrhythmia(14-16).

PMID- 21946768
TI  - Colorimetric assay for sulfate using positively-charged gold nanoparticles and
      its application for real-time monitoring of redox process.
AB  - A flexible nanoparticle-based sulfate assay is demonstrated in which the
      positively-charged gold nanoparticles (cysteamine-AuNPs) act as indicator. The
      aggregation of cysteamine-AuNPs is selectively induced by sulfate, which allows
      the rapid colorimetric sensing of sulfate without any precipitant, sample
      preparation and specific instruments. In this work, the cysteamine-AuNPs probe
      has been successfully applied to the colorimetric detection of sulfate and
      demonstrates superior sensitivity with a detection limit of sulfate of ~50 ppb. A
      surprise finding is that the proposed probe can achieve the goal of real-time
      monitoring and translating a redox process into an appreciable color change via
      the aggregation of nanoparticles. This is a novel application of a positively
      charged AuNPs-based nanoprobe for sulfate detection, kinetic study of the redox
      process, and opens up new opportunities for design of more novel colorimetric
      strategies and expansion of AuNPs-based application in different fields.

PMID- 21946769
TI  - Association of physical activity and atrial fibrillation.
AB  - BACKGROUND: There is controversy regarding the association of physical activity
      (PA) and atrial fibrillation (AF). This systematic review aims to summarize the
      evidence regarding the association of PA at different levels and AF. METHODS: A
      structured search of databases was performed until December 2009. Studies that
      investigated the association between PA and AF were included and assessed by 2
      researchers according to selection criteria and methodological quality. The
      overall quality of evidence was rated according to the Grade system. RESULTS: Of
      855 publications, 10 met the inclusion criteria. The risk of uncontrolled bias
      and confounding was profound and there was substantial heterogeneity regarding
      observed associations. One methodologically rigorous study reported substantial
      risk reductions associated with moderate intensity PA. Another indicated modest
      increases in risk with high levels of vigorous PA. Five methodologically less
      reliable studies reported large increases in risk due to regular sport practice.
      CONCLUSION: The overall quality of evidence indicating increases in risk of AF is
      low. Most reports of large increases in risk appear to be overestimated
      substantially. In light of the public health importance of regular PA,
      contradictory recommendations concerning the participation in PA should be
      considered cautiously before more rigorous studies have investigated this issue.

PMID- 21946770
TI  - Radiographic predictors of visual outcome in orbital compartment syndrome.
AB  - PURPOSE: The goal of this study is to evaluate parameters on orbital CT as
      predictors of visual outcome in orbital compartment syndrome from retrobulbar
      hematoma or orbital cellulitis. The study will assess the assertion that certain
      patients are anatomically predisposed to vision loss in these conditions.
      METHODS: A retrospective chart review of consecutive patients with the diagnosis
      of either orbital cellulitis or orbital hematoma from the clinic of a single
      provider in an academic practice from 2006 to 2009 was performed. Exclusion
      criteria included preexisting vision loss, lack of CT scan for analysis, or lack
      of 1-month follow up for final visual acuity. Measurements of final visual
      acuity, medial wall length, lateral wall length, distance from the globe to the
      apex, and a novel measurement of posterior globe tenting (stretch angle) were
      obtained. Patients were divided into 2 groups: normal visual acuity and vision
      loss. Statistical analysis was performed to identify significant differences
      between the 2 groups. RESULTS: The normal vision group consisted of 11 patients,
      all with vision of 20/30 or better. The average length of the medial and lateral
      wall was 43.9 and 41.6 mm, respectively. The average distance from the globe to
      the apex was 26.3 mm in the uninvolved eye and 30.3 mm in the involved eye,
      resulting in an average difference of 4.18 mm. The average stretch angle
      measurement was 28.9 degrees  in the uninvolved eye and 28.5 degrees  in the
      involved eye, resulting in an average difference of 0.41 degrees . The vision
      loss group consisted of 4 patients, all with vision of count fingers or worse.
      The average length of the medial and lateral wall was 46.9 and 45.7 mm,
      respectively. The average distance from the globe to the apex was 32.2 mm in the
      uninvolved eye and 36.7 mm in the involved eye, resulting in an average
      difference of 4.50 mm. The average stretch angle measurement was 32.3 degrees  in
      the uninvolved eye and 21.1 degrees  in the involved eye, resulting in an average
      difference of 11.2 degrees . The difference in stretch angle between eyes in the
      vision loss and normal vision groups were found to be highly significant with a p
      value of less than 0.001. The difference between the 2 orbits for globe to apex
      is a rough measurement of proptosis and was not statistically different in the 2
      groups (p = 0.71), whereas the length from the globe to the apex in the
      uninvolved eye was statistically different between the vision loss group and
      normal vision group (p = < 0.001). CONCLUSIONS: Orbital compartment syndrome is a
      potentially vision-threatening condition. Minimal objective data are currently
      available in the literature to guide physicians in making clinical judgments
      regarding these patients. The results of this study indicate that comparing the
      novel stretch angle between the patient's 2 eyes and measuring the length from
      the globe to the orbital apex can help identify patients at risk for poor visual
      outcome. This study provides objective measurements that can aid ophthalmologists
      and radiologists in determining the relative threat to vision in patients
      presenting with orbital compartment syndrome from orbital cellulitis or
      retrobulbar hematoma. Hopefully, the data can help select patients that may
      benefit from more aggressive intervention and will ultimately result in superior
      visual outcomes.

PMID- 21946771
TI  - Composite septo-retractor recession; a surgical technique for lower-eyelid
      retraction and review of the literature.
AB  - PURPOSE: To report the outcomes of a technique for correcting lower-eyelid
      retraction with composite recession of the inferior retractor and orbital septum
      complex, release of the lateral horn of the lower-eyelid retractors, and the
      orbito-malar ligament (OML) followed by skin, orbicularis, and conjunctival
      advancement. METHODS: We performed a retrospective, noncomparative review of
      consecutive procedures performed on patients with lower-eyelid retraction
      undergoing composite septo-retractor recession for lower-eyelid retraction over a
      4-year period, performed or supervised by a single surgeon (RM). Outcomes are
      based on postoperative standard photographs, including central pupil to lower
      eyelid distance, inferior scleral show, and subjective improvement in lower
      eyelid lateral flare. RESULTS: We reviewed 26 eyes of 16 patients (12 men, 4
      women; mean age, 61.0 +/- 14.3 years). Causes of lower-eyelid retraction included
      involutional (n = 6), thyroid orbitopathy (n = 4), previous lower-eyelid surgery
      (n = 3), mechanical secondary to proptosis (n = 1), Crouzon syndrome (n = 1), and
      longstanding facial nerve palsy (n = 1). Mean lower-eyelid elevation achieved was
      1.4 mm +/- 1.3 mm (range, 0.2 to 6.6 mm; p = 0.001). Scleral show improved by 1.0
      +/- 0.7 mm (range, 0.0 to 2.9; p = <0.001). Preoperatively, all patients had an
      altered lower-eyelid contour with lateral flare, 89% cases being graded
      "significant." Lower-eyelid contour improved postoperatively, with only 19%
      graded "significant" lateral flare (p = <0.0001). No significant complications
      occurred, although one patient required excision of a secondary lateral canthal
      cyst. CONCLUSION: Composite recession of the inferior retractor and orbital
      septum complex combined with release of the inferior retractor lateral horn and
      the OML significantly improves lower-eyelid height and contour in cases of lower
      eyelid retraction and should be considered a useful option for this condition.

PMID- 21946772
TI  - A unique case of IgG4 sclerosing dacryocystitis.
AB  - IgG4-related ocular adnexal disease, a relatively recently described clinical
      entity, is important to diagnose because during the acute phase, it responds
      favorably to corticosteroid treatment. The diagnosis can be confirmed by simple
      blood tests and histology. IgG4-related dacryoadenitis and generalized orbital
      disease have been reported; however, this is the first report of IgG4-related
      disease of the lacrimal sac. We describe an 80-year-old female who presented with
      a painless erythematous indurated swelling in the right lacrimal sac area with
      complete obstruction of the right nasolacrimal system. A 9-mm lacrimal sac mass
      was noted on CT dacryocystogram. Blood tests revealed an elevated serum IgG4
      level, and the lacrimal sac histology was characteristic of IgG4-related disease.
      Corticosteroid treatment was declined by the patient. She was kept under close
      observation for signs of progression, systemic involvement, and potential
      malignant transformation.

PMID- 21946773
TI  - Doxycycline for treatment of blepharochalasis via inhibition of matrix
      metalloproteinases.
AB  - Two cases of blepharochalasis were studied. In Case 1, a 16-year-old male
      presented with the history and clinical features of blepharochalasis. A positive
      tissue biopsy for matrix metalloproteinases suggested a benefit from treatment
      with doxycycline. The patient remained disease-free for 18 months following
      commencement of doxycycline. In Case 2, a 21-year-old male with a 5-month history
      of swelling affecting his upper eyelids was diagnosed with blepharochalasis. He
      received an 8-month course of doxycycline and remained symptom-free on review 2
      months after treatment cessation. While the pathogenesis of blepharochalasis has
      remained uncertain, an immune mechanism has been suspected. The presence of
      matrix metalloproteinases in the tissue biopsy of our first patient supports such
      an immune mechanism. As doxycycline inhibits matrix metalloproteinase activity,
      it may provide an effective and well-tolerated treatment alternative for cases of
      blepharochalasis for which surgery has previously been the only treatment option.

PMID- 21946774
TI  - First investigation on charge-discharge reaction mechanism of aqueous lithium ion
      batteries: a new anode material of Ag2V4O11 nanobelts.
AB  - Aqueous lithium ion batteries have been widely considered as promising "green"
      batteries due to several advantages, such as low toxicity, low cost, high safety,
      as well as high ion conductivity. But unlike the great effort devoted to
      understanding the lithium insertion/extraction process in non-aqueous lithium ion
      batteries, the knowledge about this in aqueous electrolytes is still lacking
      research at present. In this work, taking a new anode material of single
      crystalline Ag(2)V(4)O(11) nanobelts as an example, we investigated the charge
      discharge reaction mechanism of aqueous lithium ion batteries for the first time.
      A two-step reaction mechanism was proposed and it was also deduced that
      crystallinity loss of the electrode materials and partial irreversibility of
      silver oxidation are the key reasons for rapid capacity fading. We expect this
      work to provide a scientific platform that could help to investigate and evaluate
      other electrode materials in this research area.

PMID- 21946775
TI  - Biomarkers: Coronary artery calcium is a better risk marker than hsCRP.

PMID- 21946777
TI  - Coronary artery disease: Dalcetrapib safely raises HDL-cholesterol level in the
      phase IIb dal-PLAQUE trial.

PMID- 21946780
TI  - Density functional for ternary non-additive hard sphere mixtures.
AB  - Based on fundamental measure theory, a Helmholtz free energy density functional
      for three-component mixtures of hard spheres with general, non-additive
      interaction distances is constructed. The functional constitutes a generalization
      of the previously given theory for binary non-additive mixtures. The diagrammatic
      structure of the spatial integrals in both functionals is of star-like (or tree
      like) topology. The ternary diagrams possess a higher degree of complexity than
      the binary diagrams. Results for partial pair correlation functions, obtained via
      the Ornstein-Zernike route from the second functional derivatives of the excess
      free energy functional, agree well with Monte Carlo simulation data.

PMID- 21946776
TI  - Neural mechanisms of atrial arrhythmias.
AB  - The past 5 years have seen great advances in the knowledge of neural mechanisms
      of atrial arrhythmogenesis. Direct autonomic nerve recordings demonstrate that
      simultaneous sympathovagal discharges and intrinsic cardiac nerve activities are
      common triggers of paroxysmal atrial tachycardia and atrial fibrillation. While
      activity of the autonomous nervous system (ANS) is crucial in triggering
      paroxysmal atrial fibrillation, a high incidence of sympathovagal co-activation
      at baseline is associated with a high vulnerability to pacing-induced sustained
      atrial fibrillation, suggesting that ANS has a role in the development of
      persistent atrial fibrillation. Modulation of ANS activity may constitute an
      important therapeutic strategy for the management of atrial tachyarrhythmias.
      Specifically, continuous, low-level stimulation of the left cervical vagus nerve
      effectively suppresses atrial tachyarrhythmias by reducing the nerve activity of
      the stellate ganglion. Clinically, compared with pulmonary vein isolation alone,
      the addition of ablation of intrinsic cardiac ganglia may confer better outcomes
      for patients with paroxysmal atrial fibrillation. These findings suggest that
      further investigation of the neural mechanisms of atrial arrhythmias might lead
      to better management of patients with atrial arrhythmias. In this article, we
      review the role of the ANS in the induction and maintenance of atrial arrhythmias
      and the role of neural modulation as a treatment strategy for atrial arrhythmias.

PMID- 21946778
TI  - Acute coronary syndromes: Antithrombotics in ACS--moving beyond unfractionated
      heparin.

PMID- 21946781
TI  - Preparation of synaptoneurosomes from mouse cortex using a discontinuous percoll
      sucrose density gradient.
AB  - Synaptoneurosomes (SNs) are obtained after homogenization and fractionation of
      mouse brain cortex. They are resealed vesicles or isolated terminals that break
      away from axon terminals when the cortical tissue is homogenized. The SNs retain
      pre- and postsynaptic characteristics, which makes them useful in the study of
      synaptic transmission. They retain the molecular machinery used in neuronal
      signaling and are capable of uptake, storage, and release of neurotransmitters.
      The production and isolation of active SNs can be problematic using medias like
      Ficoll, which can be cytotoxic and require extended centrifugation due to high
      density, and filtration and centrifugation methods, which can result in low
      activity due to mechanical damage of the SNs. However, the use of discontinuous
      Percoll-sucrose density gradients to isolate SNs provides a rapid method to
      produce good yields of translationally active SNs. The Percoll-sucrose gradient
      method is quick and gentle as it employs isotonic conditions, has fewer and
      shorter centrifugation spins and avoids centrifugation steps that pellet SNs and
      cause mechanical damage.

PMID- 21946782
TI  - The polymorphism of ice: five unresolved questions.
AB  - Our recent discovery of three new phases of ice has increased the total number of
      known distinct polymorphs of ice to fifteen. In this Perspective article, we give
      a brief account of previous work in the field, and discuss some of the
      particularly interesting open questions that have emerged from recent studies.
      These include (i) the effectiveness of acid and base dopants to enable hydrogen
      ordering processes in the ices, (ii) the comparison of the calorimetric data of
      some of the crystalline phases of ice and low-density amorphous ice, (iii) the
      disagreement between the experimental ice XV structure and computational
      predictions, (iv) the incompleteness of some of the hydrogen order/disorder pairs
      and (v) the new frontiers at the high and negative pressure ends of the phase
      diagram.

PMID- 21946784
TI  - Meta-analysis of wavefront-guided vs. wavefront-optimized LASIK for myopia.
AB  - PURPOSE: To detect possible differences in clinical outcomes between wavefront
      guided laser in situ keratomileusis (LASIK) and wavefront-optimized LASIK for the
      treatment of myopia. METHODS: A comprehensive literature search of Cochrane
      Library, MEDLINE, and EMBASE to identify relevant trials comparing LASIK with
      wavefront-guided and wavefront-optimized. A meta-analysis was performed on the
      results of the reports. Statistical analysis was performed using RevMan 5.0
      software. RESULTS: Seven articles describing a total of 930 eyes were identified.
      There were no statistically significant differences in the final proportion of
      eyes achieving uncorrected distance visual acuity of 20/20 or better [odds ratio,
      1.04; 95% confidence interval (CI), 0.66 to 1.65; p = 0.86], manifest refractive
      spherical equivalent within +/- 0.50 D of the target (odds ratio, 0.96; 95% CI,
      0.53 to 1.75; p = 0.90). No patient lost >= 2 lines of distance-corrected visual
      acuity at posttreatment. The changes in higher order aberrations were not
      statistically significant different between the two groups with preoperative root
      mean-square (RMS) higher order aberrations <0.3 MUm (weighted mean difference,
      0.01; 95% CI, -0.02 to 0.04; p = 0.57). However, wavefront-guided had a
      significant better postoperative aberration profile than wavefront-optimized with
      preoperative RMS higher order aberrations >0.3 MUm (weighted mean difference, 
      0.10; 95% CI, -0.15 to -0.06; p < 0.00001). CONCLUSIONS: Both wavefront-guided
      and wavefront-optimized LASIK have shown excellent efficacy, safety, and
      predictability. The wavefront-guided technology may be a more appropriate choice
      for patients who have preoperative RMS higher order aberrations >0.3 MUm.

PMID- 21946783
TI  - Intraocular pressure, ethnicity, and refractive error.
AB  - PURPOSE: The ethnically diverse Collaborative Longitudinal Evaluation of
      Ethnicity and Refractive Error (CLEERE) Study cohort provides a unique
      opportunity to explore associations among intraocular pressure (IOP), ethnicity,
      and refractive error while adjusting for potential confounding variables.
      METHODS: Mixed linear models were used to examine the effect of age, refractive
      error (cycloplegic auto-refraction), ethnicity, sex, and measurement protocol on
      IOP (Tono-pen) in 3777 children, aged 6 to 14 years at their first CLEERE visit
      (1995-2009). Children who became myopic during follow-up were used to examine the
      relationship between time since myopia onset and IOP. Clinically meaningful
      differences in IOP were preset at >2 mm Hg. RESULTS: IOP differed among
      refractive error categories with higher IOP in children with low/moderate myopia
      than those with high hyperopia (differences <1 mm Hg). There was a statistically
      significant relationship between age and IOP that depended on ethnicity
      (interaction p < 0.0001) and measurement protocol (interaction p < 0.0001). The
      relationship between sex and IOP depended on measurement protocol (interaction p
      = 0.0004). For children who became myopic during follow-up, the adjusted mean IOP
      showed a significant decline for only Asian (p = 0.024) and white children (p =
      0.004). As with other statistically significant results, these changes in mean
      adjusted IOPs from 2 years before to 2 years after myopia onset were <2 mm Hg.
      CONCLUSIONS: Small but significant differences in IOP by refractive error
      category were found in this ethnically diverse cohort of children. Relationships
      between IOP and age, ethnicity, sex, and measurement protocol were complicated by
      significant interactions between these parameters. Longitudinal analysis of
      children before and after myopia onset showed changes in IOP over time that
      varied by ethnicity. Higher IOPs before and at myopia onset were not present in
      all ethnic groups, with differences before and after onset too small to suggest a
      role for IOP in the onset of myopia.

PMID- 21946785
TI  - Non-compliance with contact lens wear and care practices: a comparative analysis.
AB  - PURPOSE: To compare the effects of existing patient awareness of lens-related
      complications and underlying risk factors on actual patient behavior during
      contact lens wear and care practices in two different clinical study populations.
      METHODS: Established contact lens wearers (n = 281) completed an anonymous
      written questionnaire on presenting to their habitual eye care practitioner in
      the Dallas-Fort Worth metroplex. Data were analyzed and compared against a second
      study population, which comprised established contact lens wearers (n = 152) who
      were sequentially evaluated after their routine contact lens examination at the
      University of Texas Southwestern Medical Center at Dallas, TX (UTSW). All
      patients were questioned regarding his or her lens care practices and knowledge
      of complications and risk factors associated with contact lens wear. RESULTS:
      Fifty-eight percent of patients in the general community could identify by name a
      complication associated with lens wear compared with 91% within the medical
      center. The most frequent complications reported were related to comfort and
      handling (72%, Dallas-Fort Worth) and infection (47%, UTSW). The majority of
      patients could correctly identify risk factors associated with lens-related
      complications; awareness for topping-off solutions, tap water exposure, and
      hygiene varied between groups. Overall, 85% of patients perceived themselves as
      compliant with their lens wear and care practices. Using a standard scoring model
      to determine actual compliance, 2% of patients demonstrated good compliance;
      however, only 0.4% of patients were fully compliant with contact lens wear and
      care practices. CONCLUSIONS: The data reveal some study bias in complication and
      risk awareness between populations; however, despite this limitation, a
      significant proportion of patients exhibited actual non-compliant behavior
      despite acknowledged awareness of risk. Although most patients consider
      themselves to be complying with standard practitioner guidelines for lens wear
      and care practices, essentially all contact lens wearing patients exhibit
      behavioral non-compliance with resulting increased risk for significant
      complications.

PMID- 21946787
TI  - It doesn't get any better than this...

PMID- 21946788
TI  - Is emotional competence a viable component in today's work environment?
AB  - This descriptive study explores the concept of emotional competence in practicing
      registered nurses. Registered nurses were asked to identify interactions of
      emotional competence that they experienced on the nursing unit. Content analysis
      revealed deficits in emotional competence in the following themes: self
      awareness, mood management, self-motivation, empathy, and managing relationships.
      Results identified emotionally competent behaviors as being desirable and vital
      to building strong teams and interdisciplinary networks.

PMID- 21946786
TI  - Vision test variability in retinitis pigmentosa and psychosocial factors.
AB  - PURPOSE: We explored whether greater amounts of short-term variability in visual
      acuity (VA), contrast sensitivity (CS), or visual field (VF) in retinitis
      pigmentosa (RP) was related to disease severity or psychosocial factors. METHODS:
      We obtained spectral domain-optical coherence tomography in 27 RP subjects and
      determined variability (SD) of VA, CS, and VF during a mean of 16 tests self
      administered at home on a personal computer twice a week. Subjects completed the
      Positive and Negative Affect Schedules at each personal computer-test session,
      and SF-36 general health and Beck Depression Inventory questionnaires on one
      occasion. RESULTS: There was a 0.10 log unit increase in VA variability for every
      0.58 logMAR increase (worse mean VA) (p = 0.001). For subjects with reduced
      foveal thickness, mean VA explained more of the total VA variability than foveal
      thickness (R2 = 0.72 and 0.46, respectively, in simple linear regressions). There
      was a statistically significant 4.3% increased log VF area variability for every
      50% mean log VF area decrease (p < 0.001); explaining most of the total
      variability in log VF area variability (R2 = 0.44). When controlling for mean log
      VF area, there was a statistically significant increase in log VF area
      variability for subjects with greater than minimal depressive symptoms (p =
      0.015), with increased mean irritability scores (p = 0.02), decreased SF-36
      physical functioning subscale scores (p = 0.03), or decreased mean score for
      feeling active, strong, and proud (p = 0.008) (adjusted R2 = 0.62). CS
      variability was low and not statistically significantly related to mean CS,
      macular thickness, or psychosocial factors. CONCLUSIONS: Increased VA and VF
      variability was predicted largely by increased RP severity. Greater VF
      variability occurred in subjects with reduced VF who reported less physical
      activity or increased negative psychosocial states. These associations should be
      considered during clinical examinations and trials for RP.

PMID- 21946789
TI  - From student to emergency nurse: a qualitative study of an educational support
      seminar.
AB  - The purpose of this qualitative study was to document the transition experience
      of new nursing graduates who participated in an educational support seminar
      during their first year of emergency room (ER) practice. Study participants
      reported that the seminar provided learning and nurturing that facilitated their
      integration into the ER team, influenced their decision to stay in the ER, and
      grounded the process of their professionalization. Important considerations
      regarding education, professionalization, and leadership emerged.

PMID- 21946790
TI  - The socialization process of newly graduated nurses into a clinical setting: role
      of the clinical nurse educator.
AB  - This article is a review and synthesis of the literature related to the
      socialization of newly graduated nurses. Personal experience and standards frame
      the clinical nurse educator role in facilitating learner development and
      socialization. Successful strategies to improve the socialization process of
      newly graduated nurses from the literature and recommendations for the future are
      presented.

PMID- 21946791
TI  - Pilot testing an educational intervention to improve communication with patients
      with dementia.
AB  - Approximately one quarter of all hospitalized patients over age 75 years have a
      secondary diagnosis of dementia. A unique hospital-wide program to encourage
      appropriate communication techniques with patients who have dementia was provided
      to all departments of a hospital. Evaluation indicated improvement in some
      communication techniques. Additional education is needed to disperse the
      information to as many staff as possible and to sustain the change.

PMID- 21946792
TI  - Evidence-based practice and a nursing journal club: an equation for positive
      patient outcomes and nursing empowerment.
AB  - Healthcare organizations are interested in promoting best patient outcomes and a
      shared-governance, professional development environment for nurses. A nursing
      journal club achieves the goal of patients receiving evidence-based care by
      empowered staff leading the journey. This article will demonstrate the successful
      process for implementing a hospital-wide nursing journal club.

PMID- 21946793
TI  - Clinical expert facilitators of evidence-based practice: a community hospital
      program.
AB  - A 1-year program for select clinical nurse experts led to increased comfort in
      using evidence-based practice strategies. Nurses identified specific barriers and
      facilitators for evidence-based practice efforts, accomplished individual goals,
      and saw changes in their practice roles. Results from the program and its
      evaluation are that staff can benefit from such an effort (4-day course with
      specific follow-up activities).

PMID- 21946794
TI  - The successful redesign of a student nurse extern program.
AB  - In this article, the authors emphasize the importance of a student nurse extern
      program in creating a pipeline for qualified bedside nurses. Through
      collaboration with the human resources department and the nurse management group,
      professional development educators in one hospital redesigned and reenergized the
      student nurse extern program to meet the needs of the externs and the healthcare
      system.

PMID- 21946796
TI  - Code blue: chaos or control, an educational initiative.
AB  - Participation in a cardiopulmonary resuscitation team can create pandemonium
      among novice as well as experienced healthcare providers. Staff development
      educators, faced with the challenge of providing continuous education to improve
      efficiency in code organization and management, may benefit from lessons learned
      in the field. This author describes an institution's initiative to address
      multidisciplinary code blue education using a creative acronym coupled with
      multilevel didactic and simulation exercises.

PMID- 21946797
TI  - NNSDO update.

PMID- 21946798
TI  - Nursing professional development: stories, tips, and techniques.

PMID- 21946799
TI  - Physical activity differences by birthplace and sex in youth of Mexican heritage.
AB  - BACKGROUND: One of the goals of Healthy People 2020 is to increase physical
      activity (PA) and reduce health disparities among different racial and ethnic
      segments of the U.S. population. Few studies have been conducted to examine PA
      differences by birthplace and sex in youth of Mexican heritage. METHODS:
      Participants were 101 youth (43 boys, 58 girls, 59% U.S.-born, 41% Mexico-born)
      who wore a sealed New Lifestyles NL-1000 pedometer for 7 consecutive days.
      RESULTS: Mexico-born youth took more steps, on average, than their U.S.-born
      counterparts (P = .038). However, moderate-to-vigorous intensity (MVI) time did
      not differ between Mexico- and U.S.-born youth (P = .146). By contrast to
      birthplace, sex-related differences were more consistent, as boys took more steps
      (P = .005) and accumulated more MVI time (P = .043) than girls. Only 4% of our
      sample met either one or both of the PA recommendations. CONCLUSIONS: We conclude
      that PA may differ by birthplace and by sex in youth of Mexican heritage, as U.S.
      born girls were the least active segment of our sample. Culturally sensitive
      interventions to increase daily PA must become a higher public health priority
      for youth of Mexican heritage, in particular, for U.S.-born girls of Mexican
      heritage.

PMID- 21946800
TI  - Fluorescence light-up recognition of DNA nucleotide based on selective abasic
      site binding of an excited-state intramolecular proton transfer probe.
AB  - DNA single-nucleotide polymorphism (SNP) detection has attracted much attention
      due to mutation-related diseases. Various fluorescence methods for SNP detection
      have been proposed and many are already in use. However, fluorescence enhancement
      for signal-on SNP identification without label modification still remains a
      challenge. Here, we find that the abasic site (AP site) in a DNA duplex can be
      developed as a binding pocket favorable for the occurrence of the excited-state
      intramolecular proton transfer (ESIPT) of a 3-hydroxyflavone, fisetin, which is
      used as a proof of concept for effective SNP identification. Fisetin binding at
      the AP site is highly selective for target thymine or cytosine facing the AP site
      by observation of a drastic increase in the ESIPT emission band. In addition, the
      target recognition selectivity based on this ESIPT process is not affected by
      flanking bases of the AP site. The binding selectivity of fisetin at the AP site
      is also confirmed by measurements of fluorescence resonance energy transfer,
      emission lifetime and DNA melting. The fluorescent signal-on sensing for SNP
      based on this fluorophore is substantially advantageous over the previously used
      fluorophores such as the AP site-specific signal-off organic ligands with a
      similar fluorescing mechanism before and after binding to DNA with hydrogen
      bonding interaction. We expect that this approach will be employed to develop a
      practical SNP detection method by locating an AP site toward a target and
      employing an ESIPT probe as readout.

PMID- 21946801
TI  - Telephone-based behavioral health assessment for older adults starting a new
      psychiatric medication.
AB  - OBJECTIVES: The purpose of this study is to explore behavioral health symptoms
      and characteristics of noninstitutionalized older adults newly started on an
      antidepressant, anxiolytic, or antipsychotic agent by nonpsychiatrist physicians.
      DESIGN: Naturalistic cohort study of older adults participating in the
      Pharmaceutical Assistance Contract for the Elderly (PACE) of the state of
      Pennsylvania. SETTING/PARTICIPANTS: Noninstitutionalized adults in Pennsylvania.
      MEASUREMENTS: Standardized scales including the Blessed Orientation-Memory
      Concentration (BOMC) test, Mini International Neuropsychiatric Interview
      (including Psychosis, Mania, Generalized Anxiety Disorder [GAD], Panic Disorder,
      and Alcohol Abuse/Dependence modules), Patient Health Questionnaire-9 (PHQ-9),
      Paykel Scale for suicide ideation, and Medical Outcomes Survey (SF-12). RESULTS:
      Participants were mostly women (83.7%) with a mean age of 79.2 years (SD 7.1).
      The average PHQ-9 score for those on antidepressants was 5.8 (5.2), with no
      statistically significant difference between medication groups (F[2, 409] = 1.48,
      p = 0.23); just seven (4.9%) of those receiving anxiolytics met criteria for an
      anxiety disorder, which was not significantly different than other medication
      classes (chi (2) = 0.83, p = 0.66). Overall, 197 (47.8%) of the sample did not
      meet criteria for a mental health disorder. Just 69 (28.8%) of those on
      antidepressants reported depression as the self-reported reason for taking the
      medication, while 91 (22.8%) of the total reported poor sleep or stressful life
      events as the reason. CONCLUSIONS: In this sample, many older persons received
      psychotropic medications despite low symptomatology, increasing the costs of care
      and possible exposure to unnecessary side effects. It is important to understand
      perceived benefit to both patient and provider of such prescribing patterns and
      work towards minimizing unnecessary use.

PMID- 21946802
TI  - The comprehensive process model of engagement.
AB  - BACKGROUND: Engagement refers to the act of being occupied or involved with an
      external stimulus. In dementia, engagement is the antithesis of apathy.
      OBJECTIVE: The Comprehensive Process Model of Engagement was examined, in which
      environmental, personal, and stimulus characteristics impact the level of
      engagement. METHODS: : Participants were 193 residents of 7 Maryland nursing with
      a diagnosis of dementia. Stimulus engagement was assessed via the Observational
      Measure of Engagement, measuring duration, attention, and attitude to the
      stimulus. Twenty-five stimuli were presented, which were categorized as live
      human social stimuli, simulated social stimuli, inanimate social stimuli, a
      reading stimulus, manipulative stimuli, a music stimulus, task and work-related
      stimuli, and two different self-identity stimuli. RESULTS: All stimuli elicited
      significantly greater engagement in comparison to the control stimulus. In the
      multivariate model, music significantly increased engagement duration, whereas
      all other stimuli significantly increased duration, attention, and attitude.
      Significant environmental variables in the multivariate model that increased
      engagement were: use of the long introduction with modeling (relative to minimal
      introduction), any level of sound (especially moderate sound), and the presence
      of between 2 and 24 people in the room. Significant personal attributes included
      Mini-Mental State Examination scores, activities of daily living performance and
      clarity of speech, which were positively associated with higher engagement
      scores. CONCLUSIONS: Results are consistent with the Comprehensive Process Model
      of Engagement. Personal attributes, environmental factors, and stimulus
      characteristics all contribute to the level and nature of engagement, with a
      secondary finding being that exposure to any stimulus elicits engagement in
      persons with dementia.

PMID- 21946803
TI  - Treating post-CABG depression with telephone-delivered collaborative care: does
      patient age affect treatment and outcome?
AB  - OBJECTIVE: To determine the nature of telephone-delivered collaborative care
      intervention provided to patients younger than and older than 60 years
      experiencing clinically significant depressive symptoms after coronary artery
      bypass graft (CABG) surgery and whether patient age is related to response and
      remission rates and delivery of care at 8-month follow-up. DESIGN: : Exploratory
      post-hoc analysis of data collected in a randomized controlled trial (RCT).
      SETTING: Seven Pittsburgh-area general hospitals. PARTICIPANTS: Fifty-eight
      depressed post-CABG patients younger than 60 and 92 comparable patients age 60
      years and older randomized to the RCT's intervention arm. MEASUREMENTS: :
      Components of collaborative care provided to patients over the 8-month study
      period and Hamilton Rating Scale for Depression scores at 8-month follow-up to
      determine response and remission status. RESULTS: There were no differences in
      the cumulative 8-month rates at which the components of collaborative care were
      delivered to the two age groups. Similar response and remission rates were also
      achieved by these groups. CONCLUSION: Older and younger patients experiencing
      clinical depression after CABG surgery can be treated with comparable components
      of collaborative care, and both age groups will achieve clinical outcomes that do
      not differ significantly from each other.

PMID- 21946804
TI  - Predictors of patient self-ratings of quality of life in Alzheimer disease: cross
      sectional results from the Canadian Alzheimer's Disease Quality of Life Study.
AB  - OBJECTIVES: To assess whether the core symptoms of Alzheimer disease (AD)
      consistently predict patient self-rated quality of life (QOL) as assessed by a
      variety of QOL measures in a large national sample of AD patients. DESIGN: Cross
      sectional. SETTING: Fifteen dementia and geriatric clinics across Canada.
      PARTICIPANTS: Community-living patients with AD (n = 370) with Mini-Mental State
      Exam (MMSE) scores greater than 10. MEASUREMENTS: Patients rated their QOL by
      using two utility indexes, the European QOL-5 Dimensions and the Quality of Well
      Being Scale, a global QOL Visual Analog Scale, and the disease-specific QOL-AD
      instrument. Cognition was assessed with the AD Assessment Scale-Cognitive
      subscale and MMSE, function with the Disability Assessment for Dementia, and
      behavioral and psychological symptoms with the Neuropsychiatric Inventory and the
      Geriatric Depression Scale (GDS). One-way analysis of variance and fully adjusted
      multiple linear regression were used to assess the relationship between core
      dementia symptoms and QOL ratings. RESULTS: The QOL measures had only small-to
      moderate correlations with each other. For all QOL measures, patient ratings were
      significantly lower among patients with more depressive symptoms. In
      multivariable analyses, the GDS score was the only significant independent
      predictor of patient self-ratings for all four QOL measures. CONCLUSIONS: Self
      rated symptoms of depression were a consistent independent predictor of patient
      rated QOL across diverse QOL measures, while performance-based measures of
      cognition and informant-based functional status were not. These findings confirm
      the importance of identifying and treating depression in patients with AD and
      endorse the use of measures of self-rated depressive symptoms and QOL as outcomes
      in AD clinical trials.

PMID- 21946806
TI  - Synthesis and characterization of cyano-substituted carborane-based compounds.
      Molecular structure of [1-(4-C7H7)-12-(C5H3-3-(CN)-3,4-(CH3)2)-C2B10H10].
AB  - The reaction of cyanogen chloride with [1-(4-C(7)H(7))-12-(C(5)H(3)-3,4
      (CH(3))(2))-C(2)B(10)H(10)] (7) was found to yield two new C(5)-substituted
      carborane cluster-based compounds, [1-(4-C(7)H(7))-12-(C(5)H(2)-3-(CN)-3,4
      (CH(3))(2))-C(2)B(10)H(10)] (8) and [1-(4-C(7)H(7))-12-(C(5)H-2,4-(CN)(2)-3,4
      (CH(3))(2))-C(2)B(10)H(10)] (9). This cyano-substitution pattern is in contrast
      to the known substitution for the analogous organic quinarene[5.6.7] system. The
      observed unique cluster-based products may be understood by a combination of
      steric and electronic effects. Compounds 8 and 9 were characterized by complete
      multinuclear NMR, (1)H-(1)H COSY NMR, (1)H-(13)C HMQC NMR, FTIR, UV-Vis, IR, MS
      data and a single crystal analysis for 8 [X-ray data for 8: C(17)H(25)B(10)N,
      monoclinic, space group P2(1)/n with cell constants a = 8.6794(17) A, b =
      11.021(2) A, c = 43.175(9) A, beta = 91.00(3) degrees , V = 4129.2(14) A(3), Z =
      8, R(1) = 0.0729, wR(2) = 0.1464].

PMID- 21946805
TI  - Predictors of family caregiver ratings of patient quality of life in Alzheimer
      disease: cross-sectional results from the Canadian Alzheimer's Disease Quality of
      Life Study.
AB  - OBJECTIVES: To assess whether the core symptoms of Alzheimer disease (AD) and
      caregiver factors consistently predict family caregiver ratings of patient
      quality of life (QOL) as assessed by a variety of QOL measures in a large
      national sample. DESIGN: : Cross-sectional. SETTING: Fifteen dementia and
      geriatric clinics across Canada. PARTICIPANTS: : Family caregivers (n = 412) of
      community-living patients with AD of all severities. MEASUREMENTS: Caregiver
      ratings of patient QOL using three utility indexes, the European Quality of Life
      5 Dimensions, Quality of Well-Being Scale and Health Utilities Index; a global
      QOL visual analogue scale; a disease-specific measure, the Quality of Life
      Alzheimer's Disease; and a generic health status measure, the Short Form-36.
      Patient cognition was assessed with the cognitive subscale of the Alzheimer's
      Disease Assessment Scale and Mini-Mental State Examination, function with the
      Disability Assessment for Dementia, and behavioral and psychological symptoms
      with the Neuropsychiatric Inventory and the Geriatric Depression Scale. Caregiver
      burden was assessed with the Zarit Burden Interview and caregiver depression with
      the Center for Epidemiologic Studies Depression scale. One-way analysis of
      variance and fully adjusted multiple linear regression were used to assess the
      relationship between patient dementia symptom and caregiver variables with QOL
      ratings. RESULTS: In multivariable analyses, caregiver ratings of patient
      function and depressive symptoms were the only consistent independent predictors
      of caregiver-rated QOL across the QOL measures. CONCLUSIONS: Caregiver ratings of
      patient function and depression were consistent independent predictors of
      caregiver-rated QOL, using a spectrum of QOL measures, while measures of patient
      cognition and caregiver burden and depression were not. These findings support
      the continued use of caregiver ratings as an important source of information
      about patient QOL and endorse the inclusion in AD clinical trials of caregiver
      rated measures of patient function, depression, and QOL.

PMID- 21946807
TI  - A newly described mutation of the CLCN7 gene causes neuropathic autosomal
      recessive osteopetrosis in an Arab family.
AB  - Neurologic manifestations in osteopetrosis are usually secondary to sclerosis of
      the skull bones. However, a rare neuropathic subtype of osteopetrosis exists that
      resembles neurodegenerative storage disorders. Unlike other forms of
      osteopetrosis, this latter form does not respond to hematopoietic stem cell
      transplantation. Preliminary studies suggest that this neuropathic form is more
      likely to be caused by mutations in the CLCN7 gene in an autosomal recessive
      manner. This study provides further evidence for this phenotype-genotype
      correlation by presenting a previously unreported mutation in the CLCN7 gene in a
      Yemeni family with the neuropathic form. This is also the first study of any
      mutation in patients with osteopetrosis of Arabic ethnicity. As literature review
      suggests that this type may be more common in Arabs, cascade genetic screening of
      early onset of autosomal recessive-osteopetrosis in patients of Arabic ancestry
      may preferably start with the CLCN7 gene rather than the TCIRG gene as is
      routinely done in clinical laboratories. Identifying a mutation in the CLCN7 gene
      in a patient with early onset of autosomal recessive-osteopetrosis may also guide
      therapeutic decisions including the option of hematopoietic stem cell
      transplantation.

PMID- 21946808
TI  - Synthesis and biological activity of optimized belactosin C congeners.
AB  - Successful biochemical studies of the natural products belactosin A and C as well
      as their more stable acylated derivatives have proved them to be powerful
      proteasome inhibitors and thereby potential candidates as pharmacologically
      relevant active compounds. In order to understand their structure-biological
      activity relations in detail and to find ways of improving their biological
      activity, four new modified belactosin congeners have been synthesized and
      tested. One of them (compound 6) turned out to be a more potent inhibitor against
      HeLa cells than the known proteasome inhibitor MG132.

PMID- 21946809
TI  - Optical and magnetic characterisation of Co3+ and Ni3+ in LaAlO3: interplay
      between the spin state and Jahn-Teller effect.
AB  - The coordination, the electronic structures and the spin of the ground state of
      Ni(3+) (3d(7)) and Co(3+) (3d(6)) introduced as impurities in LaAlO(3) are
      investigated through optical spectroscopy and magnetic measurements. The unusual
      trivalent valence state in both transition-metal ions was stabilised via a sol
      gel process followed by high oxygen pressure treatments. We show that the crystal
      field strength at the nearly O(h) transition-metal site in LaAlO(3) locates
      Ni(3+) and Co(3+) near the spin state crossover, yielding a low-spin ground state
      in both cases. We analyse how the interplay between the Jahn-Teller (JT) effect
      and the spin state affects the magnetic moment of the ion and its temperature
      dependence. The optical spectra reveal a JT effect associated with a low-spin
      ground state in Ni(3+) and with a thermally populated high-spin low-lying first
      excited state in Co(3+). The corresponding JT distortions are derived from
      structural correlations. We conclude that the JT effect is unable to stabilise
      the intermediate spin state in Co(3+). A low-spin ground state in thermal
      equilibrium with a high-spin low-lying first excited state is detected in diluted
      Co(3+)-doped LaAlO(3). These results are compared with those obtained in the
      parent pure compounds LaNiO(3) and LaCoO(3).

PMID- 21946810
TI  - Rapid urinary trypsinogen-2 test strip in the diagnosis of pancreatitis after
      endoscopic retrograde cholangiopancreatography.
AB  - OBJECTIVES: The aim of this prospective study was to evaluate the diagnostic
      value of the rapid urinary trypsinogen-2 test strip in post-endoscopic retrograde
      cholangiopancreatography (ERCP) pancreatitis. METHODS: A total of 150 patients
      were tested with the urinary trypsinogen-2 test strip and serum levels of amylase
      and lipase before ERCP and 3 hours after ERCP. The diagnostic value of urinary
      trypsinogen-2 strip test compared with that of serum amylase and lipase was
      analyzed. RESULTS: Post-ERCP pancreatitis was diagnosed in 13 (8.7%) of 150
      patients. The sensitivity, specificity, positive predictive value, negative
      predictive value, and accuracy of urinary trypsinogen-2 dipstick test at 3 hours
      after ERCP are 84.6%, 97.1%, 73.3%, 98.5%, and 96%, respectively. At the cutoff
      level of 3 times the upper reference limit, the negative predictive values of
      amylase and lipase were comparable to that urinary trypsinogen-2 strip test;
      however, their positive predictive values (42.9% and 36.4%, respectively) were
      markedly lower than that of urinary trypsinogen-2 test (73.3%). CONCLUSIONS: The
      urinary trypsinogen-2 dipstick test is a useful test for early diagnosis of post
      ERCP pancreatitis. A negative urinary dipstick test at 3 hours after the
      procedure rules out post-ERCP pancreatitis with a high probability and allows of
      early discharge plan.

PMID- 21946811
TI  - More than 9-times increased risk for pancreatic cancer among patients with acute
      pancreatitis in Chinese population.
AB  - OBJECTIVE: This study aimed to assess the risk of pancreatic cancer after acute
      pancreatitis using a nationwide population-based data set in Taiwan. METHODS: We
      conducted a retrospective cohort study of 747 patients hospitalized between 2000
      and 2003 with a principal diagnosis of acute pancreatitis (the study cohort) and
      5976 comparison patients. Stratified Cox proportional hazard regression adjusted
      for monthly income, urbanization, and geographic location of residence was used
      to calculate the 5-year hazard ratio (HR) of pancreatic cancer for the study
      versus comparison cohort. RESULTS: Of the total sample, 21 patients (0.31%)
      developed pancreatic cancer in the 5 years after index hospitalization: 11
      (1.47%) of the study group patients and 10 (0.17%) of the comparison group
      patients. After adjusting for confounders, acute pancreatitis patients were 9
      times as likely as the comparison group to develop pancreatic cancer in the
      following 5 years (HR = 9.10; 95% confidence interval, 3.81-21.76). Among
      patients with acute pancreatitis, the adjusted HR of pancreatic cancer was 40.03
      and 3.72 times greater, respectively, for those with chronic pancreatitis and for
      those without than comparison patients. CONCLUSIONS: Patients with acute
      pancreatitis have more than 9 times the risk of comparison patients to develop
      pancreatic cancer in the subsequent 5 years among the Hun Chinese ethnic
      population in Taiwan.

PMID- 21946812
TI  - Improving the diagnostic yield from staging laparoscopy for periampullary
      malignancies: the value of preoperative inflammatory markers and radiological
      tumor size.
AB  - OBJECTIVES: The role of laparoscopy in staging periampullary malignancies is to
      detect small-volume metastatic disease not visible on preoperative imaging. Owing
      to improvements in preoperative imaging, some centers no longer undertake routine
      laparoscopic staging, whereas others still find it a useful pre-exploration tool.
      METHODS: This study investigated the diagnostic yield of staging laparoscopies in
      137 consecutive potentially resectable patients with periampullary malignancies.
      Serology on presentation, tumor size on computed tomography and proinflammatory
      markers such as C-reactive protein, neutrophil-lymphocyte ratio, platelet
      lymphocyte ratio, and Glasgow Prognostic Score were also examined to see if they
      were able to identify patients more likely to benefit from staging laparoscopy.
      RESULTS: Laparoscopy identified occult disease in 16.1% of the patients. Only
      tumor diameter on cross-sectional imaging was related to an increase in
      diagnostic yield on staging laparoscopy. Area-under-curve values for tumor size
      and occult disease at laparoscopy were 0.8, with P = 0.0001. CONCLUSION: Staging
      laparoscopy is a useful adjunct to computed tomography in staging periampullary
      cancers. Tumor size (especially >45 mm) is the only preoperative marker
      predictive of unexpected occult disease and may be used to select high-risk
      patients for laparoscopic staging.

PMID- 21946813
TI  - MicroRNA miR-548d is a superior regulator in pancreatic cancer.
AB  - OBJECTIVES: This study aimed to identify microRNAs as novel biomarkers for
      improved diagnosis, prognosis prediction, and as a therapeutic target for
      pancreatic cancer. microRNAs may have a general role by acting as superordinated
      key regulators of tumorigenesis. METHODS: Individual cellular molecules of
      multiple pathways associated with pancreatic cancer were analyzed for common
      microRNA binding sites, thereby enabling the identification of key regulating
      microRNAs. The potential of the identified microRNAs was subsequently determined
      in cell culture experiments. RESULTS: Using bioinformatic pathway analyses, miR
      548d was identified to target multiple components of pancreatic cancer-related
      pathways. The effect of microRNA on pancreatic cells was determined by
      overexpression studies using PANC-1 cells, resulting in impaired cell
      proliferation because of increased apoptosis and cell cycle arrest. In addition,
      miR-548d overexpression led to a sensitization to gemcitabine. CONCLUSIONS:
      MicroRNA miR-548d was identified as a potential superior regulator for the
      development and progression of pancreatic cancer by targeting multiple factors of
      crucial pathways. Therapeutically, microRNAs with superordinate function, such as
      miR-548d, may be promising diagnostic and therapeutic tools for the future
      treatment of pancreatic cancer.

PMID- 21946814
TI  - Long-term clinical and imaging follow-up of nonoperated branch duct form of
      intraductal papillary mucinous neoplasms of the pancreas.
AB  - OBJECTIVES: The aim of our study was to perform a 10-year imaging and clinical
      prospective follow-up of patients with nonoperated branch duct (BD) intraductal
      papillary mucinous neoplasms (IPMNs) of the pancreas. METHODS: Forty-nine
      patients with BD-IPMN who displayed a low probability for malignancy were
      followed up including a clinical component and a series of imaging techniques
      such as computed tomography, magnetic resonance cholangiopancreatography, and
      endoscopic ultrasonography. RESULTS: After a mean follow-up period of 77 months,
      77.5% of patients remained free of symptoms. An increase in the size and number
      of BD cysts without mural nodules and with no significant increase of main duct
      size occurred in 18 patients at an average interval of 47 months. Five patients
      were operated on owing to recurrent pancreatitis and/or an increase in the size
      of either cysts or the main duct (mean time delay after diagnosis: 20 months).
      Pathologically, they were diagnosed as benign adenoma (n = 1) or borderline (n =
      4). CONCLUSIONS: Our long-term clinical and imaging follow-up indicated that none
      of the patients with BD-IPMNs developed malignancy. Therefore, BD-IPMNs with no
      signs of malignancy should be managed conservatively. We propose that following a
      2-year patient follow-up, biannual imaging follow-ups could be sufficient.

PMID- 21946815
TI  - Experimental and theoretical study on the absorption and fluorescence properties
      of substituted aryl hydrazones of 1,8-naphthalimide.
AB  - Absorption and fluorescence spectra in acetonitrile for a series of substituted
      aryl hydrazones of N-hexyl-1,8-naphthalimide are studied with the aim of
      potential application of the compounds for enzyme activity localization. The
      influence of the substituents on the spectral characteristics has been evaluated.
      The absorption and fluorescence energies of substituted aryl-1,8-naphthalimide
      hydrazones have been calculated with the PCM TDDFT formalism. The M06 and PBE0
      functionals, combined with the 6-31+G(d) atomic basis set, have been found to
      accurately model the excited state properties of the present set of solvated
      fluorophores. Absorption and fluorescence spectral characteristics have been
      rationalized in terms of experimental and theoretical electronic indices in order
      to assess their predictive abilities for application in designing analogues with
      good emitting properties. An excellent linear dependence is established between
      the experimental fluorescence and Hammett sigma(p)(+) substituent constants and
      on the other hand sigma(p)(+) constants correlate with the theoretically
      calculated values for the electrostatic potential at nuclei (EPN). A model for
      predicting the fluorescence properties of substituted hydrazones by means of EPN
      is drawn, including the polysubstituted derivatives, where Hammett constants are
      not applicable.

PMID- 21946817
TI  - Ventricular remodelling is a prerequisite for the induction of dofetilide-induced
      torsade de pointes arrhythmias in the anaesthetized, complete atrio-ventricular
      block dog.
AB  - INTRODUCTION: A number of predisposing factors have been suggested to be
      contributing to drug-induced torsade de pointes (TdP) arrhythmias: short-long
      short (SLS) sequence, bradycardia, timing of drug administration, anaesthesia,
      ventricular remodelling, and altered ventricular activation due to ventricular
      ectopic beats (SLS) or idioventricular rhythm (IVR). Chronic atrio-ventricular
      (AV)-block (CAVB) dogs are susceptible to dofetilide-induced TdP. METHODS AND
      RESULTS: In 32 anaesthetized animals, the relevance of ventricular remodelling
      for TdP susceptibility was studied by dofetilide [0.025 mg/kg/5 min intravenously
      (iv)] during bradycardia in the presence (CAVB, n= 18) or absence [acute atrio
      ventricular block (AVB), n= 32] of ventricular remodelling. In sub-protocols, the
      possible pro-arrhythmic effects of timing of dofetilide administration: prior to
      (n= 11), or after creation of AVB (n= 9) and relevance of SLS pacing (n= 17) was
      investigated during IVR. Dofetilide was also given after AVB when the activation
      of the ventricles was normal: pacing (1000 ms) from the high septum (n= 7) or
      abnormal but fixed from the left ventricular apex (n= 5). Torsade de pointes
      inducibility was defined as reproducible (>= 3 times) occurrence. In acute AV
      block (AAVB), dofetilide did not induce TdP spontaneously (0 of 32), whereas TdP
      was seen in 10 out of 18 serially tested dogs in CAVB (P< 0.001). The other
      factors: timing of dofetilide (0 of 11 vs. 0 of 9), SLS pacing (0 of 17 vs. 1 of
      17), or ventricular activation (0 of 7 vs. 0 of 5) did not increase TdP
      susceptibility. Beat-to-beat variability of repolarization increased after
      ventricular remodelling and was highest prior to TdP induction. CONCLUSION: In
      AAVB dogs, TdP is not spontaneously seen, whereas it is present in CAVB. This
      implies that ventricular remodelling is a prerequisite for TdP induction in this
      model.

PMID- 21946816
TI  - Lectin-based isolation and culture of mouse embryonic motoneurons.
AB  - Spinal motoneurons develop towards postmitotic stages through early embryonic
      nervous system development and subsequently grow out dendrites and axons.
      Neuroepithelial cells of the neural tube that express Nkx6.1 are the unique
      precursor cells for spinal motoneurons(1). Though postmitotic motoneurons move
      towards their final position and organize themselves into columns along the
      spinal tract(2,3). More than 90% of all these differentiated and positioned
      motoneurons express the transcription factors Islet 1/2. They innervate the
      muscles of the limbs as well as those of the body and the inner organs. Among
      others, motoneurons typically express the high affinity receptors for brain
      derived neurotrophic factor (BDNF) and Neurotrophin-3 (NT-3), the tropomyosin
      related kinase B and C (TrkB, TrkC). They do not express the tropomyosin-related
      kinase A (TrkA)(4). Beside the two high affinity receptors, motoneurons do
      express the low affinity neurotrophin receptor p75(NTR). The p75(NTR) can bind
      all neurotrophins with similar but lower affinity to all neurotrophins than the
      high affinity receptors would bind the mature neurotrophins. Within the embryonic
      spinal cord, the p75(NTR) is exclusively expressed by the spinal motoneurons(5).
      This has been used to develop motoneuron isolation techniques to purify the cells
      from the vast majority of surrounding cells(6). Isolating motoneurons with the
      help of specific antibodies (panning) against the extracellular domains of
      p75(NTR) has turned out to be an expensive method as the amount of antibody used
      for a single experiment is high due to the size of the plate used for panning. A
      much more economical alternative is the use of lectin. Lectin has been shown to
      specifically bind to p75(NTR) as well(7). The following method describes an
      alternative technique using wheat germ agglutinin for a preplating procedure
      instead of the p75(NTR) antibody. The lectin is an extremely inexpensive
      alternative to the p75(NTR) antibody and the purification grades using lectin are
      comparable to that of the p75(NTR) antibody. Motoneurons from the embryonic
      spinal cord can be isolated by this method, survive and grow out neurites.

PMID- 21946818
TI  - Coupled pacing controls rapid heart rates better than paired pacing during atrial
      fibrillation.
AB  - AIMS: Delivery of a ventricular extrastimulus shortly after the effective
      refractory period (ERP) of a sensed (coupled pacing; CP) or a paced (paired
      pacing; PP) ventricular event can instantly decrease the mechanical pulse rate
      (MPR) during rapidly conducting atrial fibrillation (AF). We compared the short
      term rate-controlling effects of CP and PP during AF with rapid ventricular
      rates. METHODS AND RESULTS: Sixteen patients with ongoing, spontaneous AF were
      examined. Mechanical pulse rate was registered via arterial pressure tracings.
      During CP a coupling interval (CI) of ERP+20 ms was used to reach an optimal
      haemodynamic effect. Paired pacing was started at a basic cycle length (CL) of
      500 ms followed by an extrastimulus with an CI of ERP+20 ms. Drive train was
      changed at 50 ms increments until the lowest MPR was reached. Proarrhythmic
      effects were characterized by the number of premature ventricular complexes
      (PVCs). Mechanical pulse rate significantly decreased in all patients during CP
      (113 +/- 9 vs. 58 +/- 4/min). Using CP the controlled rhythm remained irregular
      (CL range: 896 +/- 24-1452 +/- 67 ms) while no PVCs were observed. With different
      drive trains PP resulted in different regular MPRs (range 62 +/- 6-80 +/- 4/min),
      but the lowest MPR achieved was significantly higher in the PP group than in the
      CP. Paired pacing caused premature beats in nine patients (56%) resulting in loss
      of continuous MPR control. CONCLUSIONS: Both CP and PP can reduce the MPR during
      rapidly conducting AF. Coupled pacing is more applicable, but PP has the
      advantage to achieve different target heart rates. Paired pacing has more
      proarrhythmic effects as compared with CP.

PMID- 21946819
TI  - Right ventricular outflow pacing induces less regional wall motion abnormalities
      in the left ventricle compared with apical pacing.
AB  - AIMS: This study aimed to explore if the right ventricular outflow tract (RVOT)
      pacing is superior to right ventricular apical (RVA) pacing on the overall left
      ventricular (LV) function and regional wall motion. METHODS AND RESULTS: Sixty
      patients with atrio-ventricular (AV) block and normal ejection fraction
      undergoing dual-chamber pacemaker implantation were randomized to permanent
      ventricular stimulation either in the RVOT or the RVA. Left ventricular volume,
      ejection fraction, and LV regional wall motion were assessed by echocardiography.
      Right ventricular apical pacing had prolonged QRS duration, compared with RVOT
      pacing (154.1 +/- 26.5 vs. 120.9 +/- 22.3, P< 0.05). There were also significant
      differences in LV pre-ejection interval and interventricular mechanical delay
      (IVMD) at 12-month follow-up between the two groups, but none in the LV volume,
      left ventricular ejection fraction, and index of systolic synchrony (Ts-SD).
      During RVA pacing, the average peak systolic velocity (Sm) of 12 LV segments
      [3.5, 95% confidence interval (CI) 3.2-3.8 cm/s] had a trend of being lower
      compared with RVOT pacing (3.9, 95% CI 3.5-4.1 cm/s) (P= 0.09). Further analysis
      showed that the Sm at the inferior wall and posterior-septum wall was
      significantly decreased during RVA pacing compared with RVOT pacing. There were
      no significant differences for other LV segments. CONCLUSION: The RVOT pacing in
      AV block patients over 1 year may be superior to RVA pacing in terms of regional
      LV performance, LV global electromechanical delay, and IVMD, although
      intraventricular dyssynchrony and LV volumes do not differ. Larger trials with
      clinical endpoints are warranted to conclusively define the advantages of RVOT or
      RV septal pacing.

PMID- 21946820
TI  - Ventricular tachycardia or ventricular fibrillation occurs less often in patients
      with left bundle branch block and combined resynchronization and defibrillators
      than in patients with narrow QRS and conventional defibrillators.
AB  - AIMS: Mortality in chronic heart failure (CHF) patients with left bundle branch
      block (LBBB) is high. Cardiac resynchronization therapy (CRT) reduces symptoms
      and mortality in CHF patients with LBBB. Whether CRT promotes or prevents
      ventricular tachycardia (VT)/ventricular fibrillation (VF) remains controversial,
      however. Therefore, we aimed to analyse arrhythmia-related CRT effects and
      characterized the VT/VF incidence in CRT-defibrillator patients and matched
      controls with conventional implantable cardioverter-defibrillators (ICDs) for
      primary prevention of sudden cardiac death. METHODS AND RESULTS: We enrolled 134
      patients [110 men, left ventricular ejection fraction (LVEF) 24 +/- 8%, 71
      coronary artery disease, CRT-ICD 67, conventional ICD matched controls 67, follow
      up 31 +/- 17 months] and monitored overall survival and the time to a first VT/VF
      episode. Controls did not have LBBB. They were otherwise matched for age, LVEF,
      and follow-up duration. Gender and underlying disease did not differ between the
      groups. Kaplan-Meier analysis revealed more favourable arrhythmia-free survival
      in CRT-ICD vs. conventional ICD patients [hazard ratio (HR) 2.26, confidence
      interval (CI) 1.09-4.67, log rank P = 0.023]. The difference persisted in the
      multivariate Cox regression analysis (HR 3.25, CI 1.18-8.93, P= 0.022). Overall
      survival was similar in both groups (HR 1.45, CI 0.55-3.82, P = 0.45).
      CONCLUSIONS: Chronic heart failure patients with LBBB treated with CRT-ICD,
      experience less and delayed VT/VF episodes compared with matched controls without
      LBBB receiving conventional ICD. In the long-term, CRT appears to exert
      antiarrhythmic effects and to attenuate the particularly high arrhythmia-related
      risk of CHF patients with LBBB. The incremental benefit of adding the ICD option
      to CRT pacing in LBBB patients appears questionable.

PMID- 21946821
TI  - Atrial electromechanical function.

PMID- 21946822
TI  - Prediction of fluid responsiveness in septic shock patients:  comparing stroke
      volume variation by FloTrac/Vigileo and automated pulse pressure variation.
AB  - OBJECTIVES: The aim of this study was to assess and compare the ability of the
      automatically and continuously measured stroke volume variation (SVV) obtained by
      FloTrac/Vigileo, and pulse pressure variation (PPV) measured by an IntelliVue MP
      monitor, to predict fluid responsiveness in mechanically ventilated septic shock
      patients. METHOD: We conducted a prospective study on 42 septic shock patients.
      SVV, PPV and other haemodynamic data were recorded before and after fluid
      administration of 500 ml of 6% hydroxyethyl starch. Responders were defined as
      patients with an increase in stroke volume index of at least 15% after fluid
      loading. RESULTS: Twenty-four (57.1%) patients were classified as fluid
      responders. The baseline SVV correlated with the baseline PPV (r=0.96, P<0.001).
      SVV and PPV were significantly higher in responders than in nonresponders (15.5+/
      4.5 vs. 8.2+/-3.3% and 16.4+/-5.2 vs. 8.3+/-3.5, respectively, P<0.001 for both).
      There was no difference between the area under the receiver operating
      characteristic curves of SVV [0.92, 95% confidence interval 0.832-1.00] and PPV
      (0.916, 95% confidence interval 0.829-1.00). The optimal threshold values in
      predicting fluid responsiveness were 10% for SVV (sensitivity 91.7% and
      specificity 83.3%) and 12% for PPV (sensitivity 83.3% and specificity 83.3%). Our
      results were independent of the site of arterial catheterisation. CONCLUSION: The
      SVV, obtained by FloTrac/Vigileo, and the automated PPV, obtained by the
      IntelliVue MP monitor, showed comparable performance in terms of predicting fluid
      responsiveness in passively ventilated septic shock patients, with a regular
      cardiac rhythm and a tidal volume not less than 8 ml kg(-1).

PMID- 21946823
TI  - Do intraoperative analgesics influence oncological outcomes after radical
      prostatectomy for prostate cancer?
AB  - BACKGROUND: The potential impact of intraoperative analgesics on oncological
      outcome after radical prostatectomy is debated. Some investigators have suggested
      that use of opioids favour relapse, whereas regional analgesia and NSAIDs improve
      oncological outcomes. OBJECTIVE: To evaluate the impact of intraoperative
      analgesia (epidural and intravenous) on the incidence of biochemical recurrence
      free (BRF) survival. DESIGN, SETTING AND PARTICIPANTS: This retrospective study
      includes 1111 consecutive retropubic radical prostatectomies (RRPs) for localised
      prostate cancer, performed between 1993 and 2006. Median follow-up was 38 months
      (interquartile range 16-69). BRF survival probabilities were compared with log
      rank tests and the Cox regression model. MAIN OUTCOME MEASURES AND RESULTS:
      Epidural analgesia was used in 52% of patients, intravenous ketorolac in 25%,
      sufentanil in 97%, clonidine in 25% and ketamine in 16%. Univariate and
      multivariate analyses showed that intravenous sufentanil significantly reduced
      BRF survival rate, hazard ratio 7.78 [95% confidence interval (CI) 5.79, 9.78),
      for extracapsular extension stage pT 2 or less, hazard ratio 0.44 (95% CI 0.12,
      0.75), Gleason score at least 7, hazard ratio 1.96 (95% CI 1.65, 2.26), positive
      margin, hazard ratio 1.87 (95% CI 1.58, 2.02) and lymph node involvement, hazard
      ratio 1.77 (95% CI 1.27, 2.27, P > 0.05). In contrast, neither epidural analgesia
      nor other analgesics were associated with a statistically significant effect (P >
      0.05). CONCLUSION: This retrospective analysis suggests that intraoperative
      sufentanil administration is associated with an increased risk of cancer relapse
      after RRP, whereas epidural analgesia, with local anaesthetic and opioid, was not
      associated with a significant effect.

PMID- 21946824
TI  - Myocardial oxidative stress protection by sevoflurane vs. propofol:  a randomised
      controlled study in patients undergoing off-pump coronary artery bypass graft
      surgery.
AB  - CONTEXT: Myocardial oxidative stress plays an essential role in the pathogenesis
      of ischaemia-reperfusion injury associated with coronary artery bypass grafting
      (CABG). Both propofol and volatile anaesthetics have been shown to reduce
      reactive oxygen species in experimental and clinical studies. MAIN OBJECTIVE: To
      compare the influence of sevoflurane and propofol on myocardial oxidative stress
      markers (F2-isoprostanes and nitrates/nitrites) in coronary sinus blood samples
      from patients undergoing off-pump CABG. DESIGN AND SETTING: Randomised controlled
      clinical study of patients scheduled for off-pump CABG in a tertiary academic
      university hospital from June 2007 to August 2009. Forty patients consented to
      enrolment and were assigned to receive either propofol or sevoflurane.
      INTERVENTIONS: Upon completion of the proximal anastomosis, a retroplegia cannula
      was inserted in the coronary sinus to obtain blood samples, according to the
      study protocol. MAIN OUTCOME MEASURES: Markers of lipoperoxidation (F2
      isoprostanes) and nitrosative stress (nitrates/nitrites) were measured in
      coronary sinus blood samples at three time points: after the end of the proximal
      anastomosis (T1), after completion of all grafts (T2) and 15 min after
      revascularisation (T3). RESULTS: Of the 40 recruited patients, 38 fully completed
      the study. In the sevoflurane group (n = 20), concentrations of oxidative stress
      markers in the coronary sinus remained almost constant and were significantly
      lower than those in the propofol group (n = 18) at all time points. F2
      isoprostanes concentrations were as follows at T1: sevoflurane group 37.2 +/-
      27.5 pg ml vs. propofol group 170.7 +/- 30.9 pg ml [95% confidence interval (CI)
      112.16-155.08, P < 0.0001); at T2: sevoflurane group 31.94 +/- 24.6 pg ml vs.
      propofol group 171.6 +/- 29.7 pg ml (95% CI 119.78-159.63, P < 0.0001); and at
      T3: sevoflurane group 23.8 +/- 13.0 pg ml vs. propofol group 43.6 +/- 31 pg ml
      (95% CI 2.87-36.63, P = 0.023). CONCLUSION: In patients undergoing off-pump CABG,
      sevoflurane showed better antioxidative properties than propofol.

PMID- 21946825
TI  - Delayed recovery following laparoscopic partial hepatectomy.
AB  - We present a 42-year-old woman with unexpected coma after laparoscopic partial
      hepatectomy. MRI demonstrated ischaemic cerebral lesions. Further investigation
      revealed a patent foramen ovale. Cryptogenic stroke arising from a paradoxical
      carbon dioxide embolism was diagnosed. After 5 days of intensive care, she made a
      near complete recovery. Perioperative stroke, paradoxical emboli during surgery,
      patent foramen ovale, carbon dioxide cerebral embolism and therapeutic strategies
      are discussed.

PMID- 21946826
TI  - Xenon administration immediately after but not before or during cardiopulmonary
      bypass with cerebral air embolism impairs cerebral outcome in rats.
AB  - CONTEXT: The neuroprotective properties of xenon might improve cerebral outcome
      after cardiac surgery using cardiopulmonary bypass. However, in the presence of
      cerebral air emboli, xenon impaired cognitive and histological outcome in a rat
      cardiopulmonary bypass model, a result which is due to the property of xenon to
      expand air bubbles. OBJECTIVE: The current study was designed to assess whether
      cerebral outcome in the setting of cardiopulmonary bypass with cerebral air
      embolism could be altered by administration of xenon restricted to periods when
      the occurrence of cerebral air embolism is unlikely. DESIGN: With institutional
      review board approval, 40 rats were allocated randomly to one of four groups (n =
      10) which determined the period of xenon inhalation: 'before', 'during' or
      'after' cardiopulmonary bypass or 'none'. SETTING: Rats were subjected to 90  min
      of normothermic cardiopulmonary bypass combined with 10 small cerebral air
      emboli. Xenon was administered according to group assignment: the 'none' group
      received no xenon; in the other groups, the lungs were ventilated with 56% xenon
      before, during or after cardiopulmonary bypass and cerebral air embolism. MAIN
      OUTCOME MEASURES: Motor and cognitive outcomes were tested using the modified
      hole-board test. Cerebral infarction volumes were determined on postoperative day
      21. RESULTS: Animals that received xenon after cardiopulmonary bypass and
      cerebral air embolism had impaired motor function scores [after: median 6.6
      (range 0.25-8), before: 0.5 (0-3), during: 1.5 (0.25-2.75), none: 1 (0-1.75)] and
      cognitive performance [after: 9 (6.5-9), before: 0 (0-5.5), during: 1 (0-5.5),
      none: 1 (0-4)] compared with all other groups (P < 0.05). Administration of xenon
      after cardiopulmonary bypass and cerebral air embolism also led to larger
      cerebral infarction volumes [after: 74 MUl (54-157), before: 45 MUl (20-82),
      during: 33 MUl (23-54), none: 22 MUl (17-78)] compared with the groups that
      received xenon during cardiopulmonary bypass and cerebral air embolism or no
      xenon at all (P < 0.05). CONCLUSION: Xenon administered immediately after
      cardiopulmonary bypass and cerebral air embolism impaired motor, cognitive and
      histological outcome in rats. At no time did inhalation of xenon lead to any
      beneficial effects on cerebral outcome when compared with inhalation of nitrogen.

PMID- 21946827
TI  - Hyperglycemia in nondiabetic patients presenting with acute myocardial
      infarction.
AB  - Hyperglycemia is common in nondiabetic patients with acute myocardial infarction
      (AMI). Elevated blood glucose level may reflect a response to stress, an
      underlying abnormal glucometabolic state or both. Regardless of mechanism,
      hyperglycemia complicating AMI is associated with an inflammatory and
      prothrombotic state, depressed myocardial contractility and increased short- and
      long-term mortality. Studies are needed to define optimal monitoring and
      management of hyperglycemia in nondiabetic patients with AMI.

PMID- 21946828
TI  - Howell-Jolly bodies: a brief historical review.
AB  - Understanding the process by which red cell precursors lose their nuclei
      developed in the late 19th and early 20th centuries led to the identification of
      nuclear remnants in circulating red cells in certain pathological states,
      particularly absence or decreased function of the spleen. William Howell, an
      American, and Justin Jolly, a Frenchman, were among a number of early
      contributors to this field. Early on, their names were applied, singly or in
      tandem, to these red cell inclusions, and the eponym, Howell-Jolly bodies, has
      stuck. It was, however, not until after the mid-20th century that Howell-Jolly
      bodies were clearly differentiated from basophilic stippling and that the
      mechanisms of their formation and removal from red cells were understood.

PMID- 21946829
TI  - Frequency, determinants and outcome of pulmonary hypertension in patients with
      aortic valve stenosis.
AB  - INTRODUCTION: The frequency, causes and prognostic implications of pulmonary
      hypertension (PHT) in patients with severe aortic stenosis (AS) are not well
      defined. The objectives of this study were to determine the frequency of PHT
      [pulmonary artery systolic pressure (PASP) >50 mm Hg] in patients with severe AS,
      identify the factors associated with PHT and assess the relationship between PHT
      and clinical outcome. METHODS: Patients with severe AS (aortic valve area <=1.0
      cm) and an echocardiographic estimate of PASP were identified by using the
      institutional echocardiography laboratory database. Patients with atrial
      fibrillation, mitral valve stenosis or a mitral prosthesis were excluded from
      analysis. The associations between clinical and echocardiographic parameters and
      PHT and the relationship between PHT and outcome were examined. RESULTS: During
      the study period, 216 patients fulfilled the inclusion criteria (age: 75 +/- 11
      years; 43% men), and PHT was present in 64 patients (29.6%). By multivariate
      analysis, reduced left ventricular (LV) systolic function (LV ejection fraction
      <=45% and lower stroke volume) and impaired LV diastolic function (mitral inflow
      E/A ratio >=1.5 and greater left atrium size) were independent predictors of PHT.
      Mortality was higher among patients with PHT managed medically (adjusted hazard
      ratio, 1.87; 95% confidence interval, 1.06-3.30; P = 0.011), whereas patients
      with PHT who underwent aortic valve replacement had an excellent outcome.
      CONCLUSIONS: PHT is common in patients with AS and is related to the severity of
      LV systolic and diastolic dysfunction. PHT is associated with poorer outcome in
      medically treated patients.

PMID- 21946830
TI  - Phosphonate-functionalized large pore 3-D cubic mesoporous (KIT-6) hybrid as
      highly efficient actinide extracting agent.
AB  - A new type of radionuclide extraction material is reported based on phosphonate
      functionalities covalently anchored on the mesopore surface of 3-D cubic
      mesoporous silica (KIT-6). The easily prepared nanoporous hybrid shows largely
      superior performance in selective sorption of uranium and thorium as compared to
      the U/TEVA commercial resin and 2-D hexagonal SBA-15 equivalent.

PMID- 21946832
TI  - Proton pump inhibitor use in infants:  FDA reviewer experience.
AB  - The Food and Drug Administration has completed its review of 4 clinical trials
      evaluating the use of proton pump inhibitors (PPIs) in infants (ages 1 month to
      <12 months) for the treatment of gastroesophageal reflux disease (GERD). An
      Advisory Committee meeting was held in November 2010 to discuss the potential
      reasons why PPI use in these trials failed to show a benefit in infants with
      GERD, and directions for future study. The present review summarizes the findings
      from the clinical trials. Potential mechanisms for the failed clinical trials are
      discussed. The safety of long-term use is also discussed. As a result of our
      analysis and review, the authors agree with the Advisory Committee members that
      PPIs should not be administered to treat the symptoms of GERD in the otherwise
      healthy infant without the evidence of acid-induced disease.

PMID- 21946833
TI  - Changes in inflammation and QoL after a single dose of infliximab during ongoing
      IBD treatment.
AB  - BACKGROUND AND OBJECTIVES: Infliximab is used increasingly as maintenance therapy
      for inflammatory bowel disease (IBD); however, the effects of a single
      maintenance dose of infliximab are unclear with respect to the quality of life
      and hormones related to growth and puberty. The aim of the present study was to
      determine the time course of inflammatory, hormonal, and quality-of-life changes
      following a single dose of infliximab in the context of ongoing therapy, as
      related to presence of IBD symptoms at time of administration. METHODS: Children
      and adolescents with IBD receiving ongoing therapy with infliximab for clinical
      indications were recruited. The Pediatric Crohn's Disease Activity Index was
      determined at baseline and laboratory measures of high-sensitivity C-reactive
      protein (hsCRP) and hormones of growth and puberty were determined on days 0, 2,
      and 14. IBD-related quality of life (IMPACT III questionnaire) was tested on days
      0 and 14. Subjects who had symptoms of IBD were compared with asymptomatic
      subjects. RESULTS: Subjects overall and in the symptomatic group exhibited
      improved hsCRP by day 2 following treatment. Symptomatic subjects had higher
      Pediatric Crohn's Disease Activity Index scores and lower quality-of-life scores
      than asymptomatic subjects on day 0, whereas at day 14 there were no significant
      differences in quality-of-life scores between the 2 groups. CONCLUSIONS: Even in
      the context of ongoing treatment, a single dose of infliximab results in
      decreased hsCRP, an improvement that is particularly noted among subjects who are
      symptomatic at the time of treatment. Although randomized trials are needed,
      these observational data may assist clinicians, patients, and families regarding
      expectations about timing and extent of these changes following a single
      treatment dose.

PMID- 21946834
TI  - Observational research:  the pitfall of drawing firm conclusions about efficacy.

PMID- 21946835
TI  - Serum and tissue CD23, IL-15, and FasL in cow's-milk protein-sensitive
      enteropathy and in coeliac disease.
AB  - OBJECTIVES: The aim of the study was to explore pathogenesis and find new serum
      markers for cow's-milk-sensitive enteropathy (CMSE) and coeliac disease (CD). We
      assessed the intestinal expression and serum concentration of CD23, IL-15, and
      FasL. We hypothesised that the serum levels of CD23, a protein expressed in the
      lymphoid follicles, would be associated with lymphonodular hyperplasia (LNH), a
      feature characteristic of CMSE. We also presumed that interleukin (IL)-15 and
      FasL, functionally connected with proliferation and apoptosis of the
      intraepithelial lymphocytes (IELs), would relate with the increased numbers of
      IELs present in both CMSE and CD. METHODS: Twenty-three children with CMSE, 20
      with untreated CD, and 14 controls were studied for CD3, alpha/beta- and
      gamma/delta-expressing IELs, and for duodenal and ileal expression of CD23, FasL,
      and IL-15 by immunohistochemistry, and for serum concentration of sCD23, sFasL,
      and sIL-15 by enzyme-linked immunosorbent assay. RESULTS: There was a trend for
      increase in sCD23 serum levels in untreated CMSE and in CD (P = 0.074; P =
      0.077). CD23 was expressed in the mucosal germinal centres, but sCD23 was not
      related to presence of LNH. In CMSE, there was a trend for increase in serum
      sFasL (P = 0.07) and high levels associated with LNH (P = 0.025) and correlated
      with the IEL numbers (P < 0.05). Mucosal high endothelial venules adjacent to
      lymphoid follicles showed an intensive FasL expression. CONCLUSIONS: Serum sCD23
      shows a trend of increment in CMSE and CD, and in the latter, sCD23 level may
      provide information about the severity of villous atrophy. In CMSE, high serum
      sFasL indicates both LNH and an increase of IELs, suggesting importance of FasL
      mediated mechanisms in the pathogenesis of these features characteristic of CMSE.
      Further studies are necessary to evaluate whether intensive FasL expression in
      mucosal high endothelial venules presents a regulatory element in mucosal
      immunity.

PMID- 21946836
TI  - New prebiotic blend of polydextrose and galacto-oligosaccharides has a
      bifidogenic effect in young infants.
AB  - OBJECTIVE: The aim of the study was to evaluate the effect of infant formula with
      polydextrose (PDX) and galacto-oligosaccharides (GOS) on fecal microbiota and
      secretory IgA (sIgA). MATERIALS AND METHODS: In the present double-blind,
      randomized study, term infants received control (Enfamil Lipil) or the same
      formula with PDX/GOS (4 g/L, 1:1 ratio; PDX/GOS) for 60 days; a reference breast
      fed group was included. Formula intake, tolerance, and stool characteristics were
      collected via electronic diary and analyzed by repeated measures analysis of
      variance. Anthropometric measurements and stool samples were obtained at baseline
      and after 30 and 60 days of feeding. Fecal sIgA was measured by enzyme-linked
      immunosorbent assay and fecal bacteria by fluorescent in situ hybridization and
      quantitative real-time polymerase chain reaction (qPCR); both were analyzed by
      Wilcoxon rank sum test. RESULTS: Two hundred thirty infants completed the study.
      Infants consuming PDX/GOS had softer stools than control at all times (P <
      0.001). Using qPCR, counts in PDX/GOS were closer to the breast-fed group, tended
      to be higher than control for total bifidobacteria (P = 0.069) and
      Bifidobacterium longum (P = 0.057) at 30 days, and were significantly higher for
      total bifidobacteria and B longum at 60 days and B infantis at 30 days (P =
      0.002). No significant differences were detected between PDX/GOS and control in
      changes from baseline to 30 or 60 days for sIgA or total bifidobacteria by
      fluorescent in situ hybridization or qPCR; however, significantly higher changes
      from baseline were detected between PDX/GOS and control for B infantis at 30 days
      and B longum at 60 days (P <= 0.035). CONCLUSIONS: Infant formula with PDX/GOS
      produces soft stools and a bifidogenic effect closer to breast milk than formula
      without PDX/GOS.

PMID- 21946837
TI  - Lactose malabsorption, calcium intake, and bone mass in children and adolescents.
AB  - OBJECTIVES: The objective of the present study was to evaluate the calcium intake
      and bone mass in children and early adolescents in accordance with their
      absorption capacity to lactose. PATIENTS AND METHODS: A transversal study was
      conducted on a sample composed of 76 individuals. Lactose malabsorption status
      was determined with hydrogen breath test. The hydrogen breath test was applied
      using 2  g of lactose per kilogram of weight up to a maximum of 50  g. A hydrogen
      increment >=20  pm in relation to fasting was used to characterize lactose
      malabsorption. Two 24-hour recalls were applied for the evaluation of food
      consumption. Bone mineral content and bone mineral density were evaluated in the
      lumbar spine by dual-energy x-ray absorptiometry. RESULTS: The prevalence of
      lactose malabsorption was 61.8%. The participants were divided into 2 groups:
      lactose malabsorbers (n = 47) and lactose absorbers (n = 29). There was no
      statistically significant difference (P > 0.05) between the groups with respect
      to the intake of total calcium, milk calcium, milk, cheese, yogurt, ice cream,
      and calcium density of the diet. Additionally, there was no difference with
      respect to the bone mineral content and the bone mineral density of the lumbar
      spine. Independent from lactose absorption capacity, it was observed that the
      majority of the children and early adolescents showed calcium intake lower than
      the recommended value. CONCLUSIONS: There was no relation among lactose
      malabsorption and bone densities, bone mineral content, or calcium intake within
      the present study.

PMID- 21946838
TI  - Emerging evidence of the physical activity transition in Kenya.
AB  - BACKGROUND: Comparable data to examine the physical activity (PA) transition in
      African countries such as Kenya are lacking. METHODS: We assessed PA levels from
      urban (UKEN) and rural (RKEN) environments to examine any evidence of a PA
      transition. Nine- to twelve-year-old children participated in the study: n = 96
      and n = 73 children from UKEN and RKEN, respectively. Pedometers were used to
      estimate children's daily step count. Parental perception regarding their child's
      PA patterns was collected via questionnaire (n = 172). RESULTS: RKEN children
      were more physically active than their UKEN counterparts with a mean average
      steps per day (+/- SE) of 14,700 +/- 521 vs. 11,717 +/- 561 (P < .0001) for RKEN
      vs. UKEN children respectively. 62.5% of the UKEN children spent 0 hours per week
      playing screen games compared with 13.1% of UKEN children who spent more than 11
      hours per week playing screen games. Seventy percent of UKEN and 34% of RKEN
      parents reported being more active during childhood than their children
      respectively. CONCLUSIONS: Results of this study are indicative of a PA
      transition in Kenya. Further research is needed to gather national data on the PA
      patterns of Kenyan children to minimize the likelihood of a public health problem
      due to physical inactivity.

PMID- 21946839
TI  - Liquid electrolytes for dye-sensitized solar cells.
AB  - The present review offers a survey of liquid electrolytes used in dye-sensitized
      solar cells from the beginning of photoelectrochemical cell research. It handles
      both the solvents employed, and the prerequisites identified for an ideal liquid
      solvent, as well as the various effects of electrolyte solutes in terms of redox
      systems and additives. The conclusions of the present review call for more
      detailed molecular insight into the electrolyte-electrode interface reactions and
      structures.

PMID- 21946840
TI  - Associations between hospital and patient characteristics and breast cancer
      patients' satisfaction with nursing staff.
AB  - BACKGROUND: Only a few studies have investigated the association between hospital
      characteristics and breast cancer patients' satisfaction with nursing staff.
      OBJECTIVE: The aim of this study was to determine whether the satisfaction of
      newly diagnosed breast cancer patients with nursing staff correlates with
      hospital characteristics after taking the relevant patient characteristics into
      account. METHODS: Multilevel regression analysis was applied, combining survey
      data from newly diagnosed breast cancer patients regarding their characteristics
      and satisfaction with nursing staff with data on the characteristics of the
      hospitals in which the patients were treated. RESULTS: Data from 2945 patients
      from 81 hospitals were analyzed in multilevel logistic regression models. The
      patients were significantly more likely to be satisfied with the nursing staff in
      hospitals that employed breast care nurses (BCNs) at the time of the survey. At
      the patient level, patients were significantly more likely to be satisfied with
      nursing staff if the patients were native speakers and rated their own health
      more highly. Cross-level interaction analysis suggested that the increased
      patient satisfaction with nursing staff that resulted from employing BCNs was
      largely limited to native German-speaking patients. CONCLUSIONS: The results
      demonstrate that patient satisfaction with nursing staff is higher if BCNs are
      employed in the treatment hospital. However, only the satisfaction of native
      speakers was significantly higher when BCNs were employed. IMPLICATIONS FOR
      PRACTICE: These findings suggest that hospitals should invest in employing
      specialist nurses. Special attention should be paid to the care of non-native
      speaking patients.

PMID- 21946841
TI  - Combination therapy: Can less really be more in melanoma?

PMID- 21946843
TI  - Resistance: Cetuximab's tip to become irresistible.

PMID- 21946844
TI  - Imaging: Lighten up tumors.

PMID- 21946842
TI  - Noninvasive cell-tracking methods.
AB  - Cell-based therapies, such as adoptive immunotherapy and stem-cell therapy, have
      received considerable attention as novel therapeutics in oncological research and
      clinical practice. The development of effective therapeutic strategies using
      tumor-targeted cells requires the ability to determine in vivo the location,
      distribution, and long-term viability of the therapeutic cell populations as well
      as their biological fate with respect to cell activation and differentiation. In
      conjunction with various noninvasive imaging modalities, cell-labeling methods,
      such as exogenous labeling or transfection with a reporter gene, allow
      visualization of labeled cells in vivo in real time, as well as monitoring and
      quantifying cell accumulation and function. Such cell-tracking methods also have
      an important role in basic cancer research, where they serve to elucidate novel
      biological mechanisms. In this Review, we describe the basic principles of cell
      tracking methods, explain various approaches to cell tracking, and highlight
      recent examples for the application of such methods in animals and humans.

PMID- 21946845
TI  - Chemotherapy: advanced NSCLC--should we use doublets in elderly patients?

PMID- 21946846
TI  - Slowed relaxation and preserved maximal force in soleus muscles of mice with
      targeted disruption of the Serca2 gene in skeletal muscle.
AB  - Sarcoplasmic reticulum Ca(2+) ATPases (SERCAs) play a major role in muscle
      contractility by pumping Ca(2+) from the cytosol into the sarcoplasmic reticulum
      (SR) Ca(2+) store, allowing muscle relaxation and refilling of the SR with
      releasable Ca(2+). Decreased SERCA function has been shown to result in impaired
      muscle function and disease in human and animal models. In this study, we present
      a new mouse model with targeted disruption of the Serca2 gene in skeletal muscle
      (skKO) to investigate the functional consequences of reduced SERCA2 expression in
      skeletal muscle. SkKO mice were viable and basic muscle structure was intact.
      SERCA2 abundance was reduced in multiple muscles, and by as much as 95% in soleus
      muscle, having the highest content of slow-twitch fibres (40%). The Ca(2+) uptake
      rate was significantly reduced in SR vesicles in total homogenates. We did not
      find any compensatory increase in SERCA1 or SERCA3 abundance, or altered
      expression of several other Ca(2+)-handling proteins. Ultrastructural analysis
      revealed generally well-preserved muscle morphology, but a reduced volume of the
      longitudinal SR. In contracting soleus muscle in vitro preparations, skKO muscles
      were able to fully relax, but with a significantly slowed relaxation time
      compared to controls. Surprisingly, the maximal force and contraction rate were
      preserved, suggesting that skKO slow-twitch fibres may be able to contribute to
      the total muscle force despite loss of SERCA2 protein. Thus it is possible that
      SERCA-independent mechanisms can contribute to muscle contractile function.

PMID- 21946847
TI  - Defined criteria for auxiliary subunits of glutamate receptors.
AB  - Pore-forming subunits of ion channels show channel activity in heterologous
      cells. However, recombinant and native channels often differ in their channel
      properties. These discrepancies are resolved by the identification of channel
      auxiliary subunits. In this review article, an auxiliary subunit of ligand-gated
      ion channels is defined using four criteria: (1) as a Non-pore-forming subunit,
      (2) direct and stable interaction with a pore-forming subunit, (3) modulation of
      channel properties and/or trafficking in heterologous cells, (4) necessity in
      vivo. We focus particularly on three classes of ionotropic glutamate receptors
      and their transmembrane interactors. Precise identification of auxiliary subunits
      and reconstruction of native glutamate receptors will open new directions to
      understanding the brain and its functions.

PMID- 21946848
TI  - Strength training increases the size of the satellite cell pool in type I and II
      fibres of chronically painful trapezius muscle in females.
AB  - While strength training has been shown to be effective in mediating hypertrophy
      and reducing pain in trapezius myalgia, responses at the cellular level have not
      previously been studied. This study investigated the potential of strength
      training targeting the affected muscles (SST, n = 18) and general fitness
      training (GFT, n = 16) to augment the satellite cell (SC) and macrophage pools in
      the trapezius muscles of women diagnosed with trapezius myalgia. A group
      receiving general health information (REF, n = 8) served as a control. Muscle
      biopsies were collected from the trapezius muscles of the 42 women (age 44 +/- 8
      years; mean +/- SD) before and after the 10 week intervention period and were
      analysed by immunohistochemistry for SCs, macrophages and myonuclei. The SC
      content of type I and II fibres was observed to increase significantly from
      baseline by 65% and 164%, respectively, with SST (P < 0.0001), together with a
      significant correlation between the baseline number of SCs and the extent of
      hypertrophy (r = -0.669, P = 0.005). SST also resulted in a 74% enhancement of
      the trapezius macrophage content (P < 0.01), accompanied by evidence for the
      presence of an increased number of actively dividing cells (Ki67(+)) post-SST (P
      < 0.001). GFT resulted in a significant 23% increase in the SC content of type II
      fibres, when expressed relative to myonuclear number only (P < 0.05). No changes
      in the number of myonuclei per fibre or myonuclear domain were detected in any
      group. These findings provide strong support at the cellular level for the
      potential of SST to induce a strong myogenic response in this population.

PMID- 21946849
TI  - The role of skeletal muscle mTOR in the regulation of mechanical load-induced
      growth.
AB  - Chronic mechanical loading (CML) of skeletal muscle induces compensatory growth
      and the drug rapamycin has been reported to block this effect. Since rapamycin is
      considered to be a highly specific inhibitor of the mammalian target of rapamycin
      (mTOR), many have concluded that mTOR plays a key role in CML-induced growth
      regulatory events. However, rapamycin can exert mTOR-independent actions and
      systemic administration of rapamycin will inhibit mTOR signalling in all cells
      throughout the body. Thus, it is not clear if the growth inhibitory effects of
      rapamycin are actually due to the inhibition of mTOR signalling, and more
      specifically, the inhibition of mTOR signalling in skeletal muscle cells. To
      address this issue, transgenic mice with muscle specific expression of various
      rapamycin-resistant mutants of mTOR were employed. These mice enabled us to
      demonstrate that mTOR, within skeletal muscle cells, is the rapamycin-sensitive
      element that confers CML-induced hypertrophy, and mTOR kinase activity is
      necessary for this event. Surprisingly, CML also induced hyperplasia, but this
      occurred through a rapamycin-insensitive mechanism. Furthermore, CML was found to
      induce an increase in FoxO1 expression and PKB phosphorylation through a
      mechanism that was at least partially regulated by an mTOR kinase-dependent
      mechanism. Finally, CML stimulated ribosomal RNA accumulation and rapamycin
      partially inhibited this effect; however, the effect of rapamycin was exerted
      through a mechanism that was independent of mTOR in skeletal muscle cells.
      Overall, these results demonstrate that CML activates several growth regulatory
      events, but only a few (e.g. hypertrophy) are fully dependent on mTOR signalling
      within the skeletal muscle cells.

PMID- 21946850
TI  - The role of sensory experience in presynaptic development is cortical area
      specific.
AB  - The postsynaptic response to a stimulus is dependent on the history of previous
      activity at that synapse. This short-term plasticity (STP) is a key determinant
      of neural network function. During postnatal development, many excitatory
      intracortical synapses switch from strong depression during early postnatal life,
      to weaker depression and in some cases facilitation in adulthood. However, it is
      not known whether this developmental switch is an innate feature of synaptic
      maturation, or whether it requires activity. We investigated this question in the
      barrel and visual cortex, two widely studied models of experience-dependent
      plasticity. We have previously defined the time course over which presynaptic
      development occurs in these two cortical areas, enabling us to make the first
      direct comparison of the role of sensory experience during synaptic development.
      We found that maturation of STP in visual cortex was unaffected by dark rearing
      from before eye opening. In marked contrast, total whisker deprivation completely
      blocked the developmental decrease in presynaptic release probability (Pr), and
      the concomitant increase in paired pulse ratio (PPR), which occur in barrel
      cortex during the third and fourth postnatal weeks. However, the developmental
      increase in the steady state response to a train of stimuli was unaffected by
      whisker deprivation. This supports a mechanistic link between Pr and the PPR, but
      dissociates Pr from the steady state amplitude during repetitive stimulation. Our
      findings indicate that sensory experience plays a greater role in presynaptic
      development at L4 to L2/3 excitatory synapses in the barrel cortex than in the
      visual cortex.

PMID- 21946851
TI  - Visual motion integration by neurons in the middle temporal area of a New World
      monkey, the marmoset.
AB  - The middle temporal area (MT/V5) is an anatomically distinct region of primate
      visual cortex that is specialized for the processing of image motion. It is
      generally thought that some neurons in area MT are capable of signalling the
      motion of complex patterns, but this has only been established in the macaque
      monkey. We made extracellular recordings from single units in area MT of
      anaesthetized marmosets, a New World monkey. We show through quantitative
      analyses that some neurons (35 of 185; 19%) are capable of signalling pattern
      motion ('pattern cells'). Across several dimensions, the visual response of
      pattern cells in marmosets is indistinguishable from that of pattern cells in
      macaques. Other neurons respond to the motion of oriented contours in a pattern
      ('component cells') or show intermediate properties. In addition, we encountered
      a subset of neurons (22 of 185; 12%) insensitive to sinusoidal gratings but very
      responsive to plaids and other two-dimensional patterns and otherwise
      indistinguishable from pattern cells. We compared the response of each cell class
      to drifting gratings and dot fields. In pattern cells, directional selectivity
      was similar for gratings and dot fields; in component cells, directional
      selectivity was weaker for dot fields than gratings. Pattern cells were more
      likely to have stronger suppressive surrounds, prefer lower spatial frequencies
      and prefer higher speeds than component cells. We conclude that pattern motion
      sensitivity is a feature of some neurons in area MT of both New and Old World
      monkeys, suggesting that this functional property is an important stage in motion
      analysis and is likely to be conserved in humans.

PMID- 21946852
TI  - Paying the piper: the cost of Ca2+ pumping during the mating call of toadfish.
AB  - Superfast fibres of toadfish swimbladder muscle generate a series of superfast
      Ca(2+) transients, a necessity for high-frequency calling. How is this
      accomplished with a relatively low rate of Ca(2+) pumping by the sarcoplasmic
      reticulum (SR)? We hypothesized that there may not be complete Ca(2+) saturation
      and desaturation of the troponin Ca(2+) regulatory sites with each twitch during
      calling. To test this, we determined the number of regulatory sites by measuring
      the concentration of troponin C (TNC) molecules, 33.8 MUmol per kg wet weight. We
      then estimated how much SR Ca(2+) is released per twitch by measuring the
      recovery oxygen consumption in the presence of a crossbridge blocker, N-benzyl-p
      toluene sulphonamide (BTS). The results agreed closely with SR release estimates
      obtained with a kinetic model used to analyse Ca(2+) transient measurements. We
      found that 235 MUmol of Ca(2+) per kg muscle is released with the first twitch of
      an 80 Hz stimulus (15(o)C). Release per twitch declines dramatically thereafter
      such that by the 10th twitch release is only 48 MUmol kg(-1) (well below the
      concentration of TNC Ca(2+) regulatory sites, 67.6 MUmol kg(-1)). The ATP usage
      per twitch by the myosin crossbridges remains essentially constant at ~25 MUmol
      kg(-1) throughout the stimulus period. Hence, for the first twitch, ~80% of the
      energy goes into pumping Ca(2+) (which uses 1 ATP per 2 Ca(2+) ions pumped), but
      by the 10th and subsequent twitches the proportion is ~50%. Even though by the
      10th stimulus the Ca(2+) release per twitch has dropped 5-fold, the Ca(2+)
      remaining in the SR has declined by only ~18%; hence dwindling SR Ca(2+) content
      is not responsible for the drop. Rather, inactivation of the Ca(2+) release
      channel by myoplasmic Ca(2+) likely explains this reduction. If inactivation did
      not occur, the SR would run out of Ca(2+) well before the end of even a 40-twitch
      call. Hence, inactivation of the Ca(2+) release channel plays a critical role in
      swimbladder muscle during normal in vivo function.

PMID- 21946853
TI  - Dynamic changes in the perceived posture of the hand during ischaemic anaesthesia
      of the arm.
AB  - Contorted 'phantom' limbs often form when sensory inputs are removed, but the
      neural mechanisms underlying their formation are poorly understood. We tracked
      the evolution of an experimental phantom hand during ischaemic anaesthesia of the
      arm. In the first study subjects showed the perceived posture of their hand and
      fingers using a model hand. Surprisingly, if the wrist and fingers were held
      straight before and during anaesthesia, the final phantom hand was bent at the
      wrist and fingers, but if the wrist and fingers were flexed before and during
      anaesthesia, the final phantom was extended at wrist and fingers. Hence, no
      'default' posture existed for the phantom hand. The final perceived posture may
      depend on the initial and evolving sensory input during the block rather than the
      final sensory input (which should not differ for the two postures). In the second
      study subjects selected templates to indicate the perceived size of their hand.
      Perceived hand size increased by 34 +/- 4% (mean +/- 95% CI) during the block.
      Sensory changes were monitored. In all subjects, impairment of large-fibre
      cutaneous sensation began distally with von Frey thresholds increasing before
      cold detection thresholds (Adelta fibres) increased. Some C fibres subserving
      heat pain still conducted at the end of cuff inflation. These data suggest that
      changes in both perceived hand size and perceived position of the finger joints
      develop early when large-fibre cutaneous sensation is beginning to degrade. Hence
      it is unlikely that block of small-fibre afferents is critical for phantom
      formation in an ischaemic block.

PMID- 21946854
TI  - Comparison of seven infant continuous positive airway pressure systems using
      simulated neonatal breathing.
AB  - OBJECTIVE: Continuous positive airway pressure is an established treatment for
      respiratory distress in neonates. Continuous positive airway pressure has been
      applied to infants using an array of devices. The aim of this experimental study
      was to investigate the characteristics of seven continuous positive airway
      pressure systems using simulated breath profiles from newborns. DESIGN:
      Experimental in vitro study. SETTING: Research laboratory in Sweden.
      INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: In vitro simulation of
      spontaneous neonatal breathing was achieved with a mechanical lung model.
      Simulation included two breath profiles, three levels of continuous positive
      airway pressure with and without short binasal prongs and different levels of
      constant leak. Pressure stability and imposed work of breathing were determined.
      Seven continuous positive airway pressure systems were tested. There were large
      differences in pressure stability and imposed work of breathing between tested
      continuous positive airway pressure systems. Neopuff and Medijet had the highest
      pressure instability and imposed work of breathing. Benveniste, Hamilton
      Universal (Arabella), and Bubble continuous positive airway pressure showed
      intermediate results. AirLife and Infant Flow had the lowest pressure instability
      and imposed work of breathing. AirLife and Infant Flow showed the least decrease
      in delivered pressure when challenged with constant leak. CONCLUSION: The seven
      tested continuous positive airway pressure systems showed large variations in
      pressure stability and imposed work of breathing. They also showed large
      differences in how well they maintain continuous positive airway pressure when
      exposed to leak. For most systems, imposed work of breathing increased with
      increasing continuous positive airway pressure level. The clinical importance of
      the difference in pressure stability is uncertain. Our results may facilitate the
      design of clinical studies examining the effect of pressure stability on outcome.

PMID- 21946855
TI  - Loss of Arnt (Hif1beta) in mouse epidermis triggers dermal angiogenesis, blood
      vessel dilation and clotting defects.
AB  - Targeted ablation of Aryl hydrocarbon receptor nuclear translocator (Arnt) in the
      mouse epidermis results in severe abnormalities in dermal vasculature reminiscent
      of petechia induced in human skin by anticoagulants or certain genetic disorders.
      Lack of Arnt leads to downregulation of Egln3/Phd3 hydroxylase and concomitant
      hypoxia-independent stabilization of hypoxia-induced factor 1alpha (Hif1alpha)
      along with compensatory induction of Arnt2. Ectopic induction of Arnt2 results in
      its heterodimerization with stabilized Hif1alpha and is associated with
      activation of genes coding for secreted proteins implicated in control of
      angiogenesis, coagulation, vasodilation and blood vessel permeability such as
      S100a8/S100a9, S100a10, Serpine1, Defb3, Socs3, Cxcl1 and Thbd. Since ARNT and
      ARNT2 heterodimers with HIF1alpha are known to have different (yet overlapping)
      downstream targets our findings suggest that loss of Arnt in the epidermis
      activates an aberrant paracrine regulatory pathway responsible for dermal
      vascular phenotype in K14-Arnt KO mice. This assumption is supported by a
      significant decline of von Willebrand factor in dermal vasculature of these mice
      where Arnt level remains normal. Given the essential role of ARNT in the adaptive
      response to environmental stress and striking similarity between skin vascular
      phenotype in K14-Arnt KO mice and specific vascular features of tumour stroma and
      psoriatic skin, we believe that further characterization of Arnt-dependent
      epidermal-dermal signalling may provide insight into the role of macro- and micro
      environmental factors in control of skin vasculature and in pathogenesis of
      environmentally modulated skin disorders.

PMID- 21946856
TI  - Therapeutic potential of fibroblast growth factor-2 for hypertrophic scars:
      upregulation of MMP-1 and HGF expression.
AB  - Although hypertrophic scars (HTSs) and keloids are challenging problems, their
      pathogenesis is not well understood, making therapy difficult. We showed that
      matrix metalloproteinase (MMP)-1 expression was downregulated in HTS compared
      with normal skin from the same patients, whereas type 1 and 3 collagen and
      transforming growth factor-beta (TGF-beta) were upregulated. These differences,
      however, were not seen in cultured fibroblasts, suggesting the involvement of
      microenvironmental factors in the pathogenesis of HTS. Fibroblast growth factor-2
      (FGF-2) highly upregulated the expression of MMP-1 and hepatocyte growth factor
      (HGF) in both HTS-derived and control fibroblasts; the upregulation was reversed
      by extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK)
      inhibitors. An animal study using human HTS tissue implanted into nude mice
      indicated that controlled-release FGF-2 resulted in significantly less weight and
      decreased hydroxyproline content in HTS. Degradation of collagen fibers in FGF-2
      treated HTS was also confirmed histologically. Western blotting showed that FGF-2
      treated HTS expressed significantly higher MMP-1 protein than control. Decreased
      MMP-1 expression may be an important transcriptional change in HTS, and its
      reversal as well as upregulation of HGF by FGF-2 could be a new therapeutic
      approach for HTS.

PMID- 21946857
TI  - Liver precursor cells increase hepatic fibrosis induced by chronic carbon
      tetrachloride intoxication in rats.
AB  - Hepatic fibrosis, the major complication of virtually all types of chronic liver
      damage, usually begins in portal areas, and its severity has been correlated to
      liver progenitor cells (LPC) expansion from periportal areas, even if the primary
      targets of injury are intralobular hepatocytes. The aim of this study was to
      determine the potential fibrogenic role of LPC, using a new experimental model in
      which rat liver fibrosis was induced by chronic carbon tetrachloride (CCl(4))
      administration for 6 weeks, in combination with chronic acetylaminofluorene
      treatment (AAF), which promotes activation of LPC compartment. Treatment with
      CCl(4) alone caused a significant increase in serum transaminase activity as well
      as liver fibrosis initiating around central veins and leading to formation of
      incomplete centro-central septa with sparse fibrogenic cells expressing alpha
      smooth muscle actin (alphaSMA). In AAF/CCl(4)-treated animals, the fibrogenic
      response was profoundly worsened, with formation of multiple porto-central
      bridging septa leading to cirrhosis, whereas hepatocellular necrosis and
      inflammation were similar to those observed in CCl(4)-treated animals. Enhanced
      fibrosis in AAF/CCl(4) group was accompanied by ductule forming LPC expanding
      from portal areas, alphaSMA-positive cells accumulation in the fibrotic areas and
      increased expression of hepatic collagen type 1, 3 and 4 mRNA. Moreover, CK19
      positive LPC expressed the most potent fibrogenic cytokine transforming growth
      factor-beta (TGFbeta) without any expression of alphaSMA, desmin or fibroblast
      specific protein-1, demonstrating that LPC did not undergo an epithelial
      mesenchymal transition. In this new experimental model, LPC, by expressing
      TGFbeta, contributed to the accumulation of alphaSMA-positive myofibroblasts in
      the ductular reaction leading to enhanced fibrosis but also to disease
      progression and to a fibrotic pattern similar to that observed in humans.

PMID- 21946858
TI  - Basophil activation test for investigation of IgE-mediated mechanisms in drug
      hypersensitivity.
AB  - Hypersensitivity reactions against non-steroidal anti-inflammatory drugs (NSAIDs)
      like propyphenazone (PP) and diclofenac (DF) can manifest as Type I-like allergic
      reactions (1). In clinical practice, diagnosis of drug hypersensitivity is mainly
      performed by patient history, as skin testing is not reliable and oral
      provocation testing bears life-threatening risks for the patient (2). Hence,
      evidence for an underlying IgE-mediated pathomechanism is hard to obtain.  Here,
      we present an in vitro method based on the use of human basophils derived from
      drug-hypersensitive patients that mimics the allergic effector reaction in vivo.
      As basophils of drug-allergic patients carry IgE molecules specific for the
      culprit drug, they become activated upon IgE receptor crosslinking and release
      allergic effector molecules. The activation of basophils can be monitored by the
      determination of the upregulation of CD63 surface expression using flow cytometry
      (3).  In the case of low molecular weight drugs, conjugates are designed to
      enable IgE receptor crosslinking on basophils. As depicted in Figure 1, two
      representatives of NSAIDs, PP and DF, are covalently bound to human serum albumin
      (HSA) via a carboxyl group reacting with the primary amino group of lysine
      residues. DF carries an intrinsic carboxyl group and, thus, can be used directly
      (4), whereas a carboxyl group-containing derivative of PP had to be
      organochemically synthesized prior to the study (1). The coupling degree of the
      low molecular weight compounds on the protein carrier molecule and their spatial
      distribution is important to guarantee crosslinking of two IgE receptor
      molecules. The here described protocol applies high performance-size exclusion
      chromatography (HPSEC) equipped with a sequential refractive index (RI) and ultra
      violet (UV) detection system for determination of the coupling degree. As the
      described methodology may be applied for other drugs, the basophil activation
      test (BAT) bears the potential to be used for the determination of IgE-mediated
      mechanisms in drug hypersensitivity.  Here, we determine PP hypersensitivity as
      IgE-mediated and DF hypersensitivity as non-IgE-mediated by BAT.

PMID- 21946859
TI  - Octahedral tilting, monoclinic phase and the phase diagram of PZT.
AB  - Anelastic and dielectric spectroscopy measurements on PbZr(1-x)Ti(x)O(3) (PZT)
      close to the morphotropic (MPB) and antiferroelectric boundaries provide new
      insight into some controversial aspects of its phase diagram. No evidence is
      found of a border separating monoclinic (M) from rhombohedral (R) phases, in
      agreement with recent structural studies supporting a coexistence of the two
      phases over a broad composition range x<0.5, with the fraction of M increasing
      toward the MPB. It is also discussed why the observed maximum of elastic
      compliance appears to be due to a rotational instability of the polarization
      linearly coupled to shear strain. Therefore it cannot be explained by extrinsic
      softening from finely twinned R phase alone, but indicates the presence also of M
      phase, not necessarily homogeneous.A new diffuse transition is found within the
      ferroelectric phase near x ~ 0.1, at a temperature T(IT) higher than the well
      established boundary T(T) to the phase with tilted octahedra. It is proposed that
      around T(IT) the octahedra start rotating in a disordered manner and finally
      become ordered below T(T). In this interpretation, the onset temperature for
      octahedral tilting monotonically increases up to the antiferroelectric transition
      of PbZrO(3), and the depression of T(T)(x) below x=0.18 would be a consequence of
      the partial relief of the mismatch between the average cation radii with the
      initial stage of tilting below T(IT).

PMID- 21946860
TI  - Concerning the deprotonation of the trimethylsulfonium ion by the
      dimethylsulfinyl anion.
AB  - As shown by deuterium labelling experiments, the deprotonation of the
      trimethylsulfonium ion (1) by the dimsyl anion (8) is accompanied by extensive
      hydrogen exchange. This cannot be explained by an acid-base equilibrium between
      the trimethylsulfonium ion (1) and the dimsyl anion (8) on one side and
      dimethylsulfonium methylide (2) and DMSO on the other side, because for
      thermodynamic reasons this process is irreversible due to the limited life-time
      of 2. Therefore, the isotopic exchange that accompanies the deprotonation is an
      indicator of a more complex deprotonation process. It is suggested that in a
      kinetically controlled reaction, a proton of 1 is transferred to the O-atom of 8
      rather than to the carbanionic centre. This means that instead of DMSO, its
      tautomer, hydroxy-methylsulfonium methylide (10), is obtained in the
      deprotonation process. Similarly, in the acid-base interaction between DMSO and
      its conjugate base 8, the formation of the DMSO tautomer 10 is kinetically
      favoured. The intermediate 10 produced in this way transfers a DMSO-derived
      proton to 1 when it intervenes in the back reaction 10 + 2->8 + 1. An alternative
      mechanism based on methyl group exchange between 1 and 8 could be excluded by a
      (13)C-labelling experiment. The hydrogen exchange according to the suggested
      scenario is taking place in competition with the reaction of dimethylsulfonium
      methylide (2) with electrophilic substrates. This explains the different degrees
      of isotopic exchange when compounds of different electrophilicities are used to
      scavenge 2 from the deprotonation-hydrogen distribution equilibria.

PMID- 21946861
TI  - A large perturbation on geometry structures, excited state properties, charge
      injection and -transporting abilities of Ir(III) complexes by different
      substituents on ligands: a DFT/TDDFT study.
AB  - The molecular geometries, electronic structures, photophysical properties, charge
      injection and -transporting abilities of a series of Ir(III) complexes with
      different carrier-transporting substituents, such as carbazole, oxadiazole and
      dimesitylboryl groups, are investigated theoretically using density functional
      theory (DFT) and time-dependent DFT (TDDFT) calculations to understand the
      influence of these substituents on the optical and electronic properties of
      Ir(III) complexes and to explore how to improve the optoelectronic properties of
      the complexes. It is found that the introduction of substituents can stabilize
      both HOMOs and LUMOs and induce variations in the energy gap between HOMO and
      LUMO. The introduction of hole-transporting carbazole substituent induces the
      blue-shift of absorption spectrum and improves the hole-injection and 
      transporting performances of complex. The introduction of electron-transporting
      oxadiazole substituent and electron-accepting dimesitylboryl substituent induces
      the red-shift in absorption spectra of complexes, improves their charge transfer
      abilities and leads to the better balance between the hole- and electron
      transporting abilities. Through Lewis acid/base interactions between B atom and
      F(-), the electronic properties of 4 show dramatic changes in the presence of F(
      ) and thus 4 can also be used as selective phosphorescent F(-) probe.

PMID- 21946862
TI  - Chemopreventive effect of different ratios of fish oil and corn oil on prognostic
      markers, DNA damage and cell cycle in colon carcinogenesis.
AB  - Fish oil (FO) rich in n-3 polyunsaturated fatty acids (PUFAs) have a protective
      role in autoimmune disorders, type 2 diabetes, rheumatoid arthritis, and cancer,
      whereas corn oil (CO) rich in n-6 PUFAs has a proinflammatory and procarcinogenic
      effect. A balanced n-3/n-6 PUFA ratio in diet rather than absolute intake of
      either may be responsible for decreasing cancer incidence. This study was
      designed to evaluate the chemopreventive effect of different ratios of FO and CO
      on prognostic markers, DNA damage, and cell cycle distribution in colon
      carcinogenesis. Male Wistar rats were divided into control, N,N'
      dimethylhydrazine dihydrochloride (DMH) treated, FO+CO(1 : 1)+DMH, and FO+CO(2.5
      : 1)+DMH. All the groups, except control, received a weekly injection of DMH for
      4 weeks. The animals were given modified AIN-76A diets and killed either 48 h
      later (initiation phase) or kept for 16 weeks (postinitiation phase). The animals
      treated with DMH in both the phases showed an increase in multiple plaque
      lesions, total sialic acid, lipid associated sialic acid, DNA damage and cell
      proliferation. However, levels of p53 in the postinitiation and cyclin D1 in both
      the phases were significantly elevated. FO+CO(2.5 : 1)+DMH treatment in both the
      phases led to a decrease in multiple plaque lesions, DNA damage, total sialic
      acid, lipid associated sialic acid as compared with the DMH treated group. There
      was a G1 arrest with a decrease in p53 and cyclin D1 levels in FO+CO(2.5 : 1) in
      both the phases whereas treatment with FO+CO(1 : 1)+DMH led to same results in
      the postinitiation phase only. This study suggests that FO+CO(2.5 : 1) is more
      effective in chemoprevention of experimental colon carcinogenesis.

PMID- 21946864
TI  - Dietary patterns and colorectal cancer:  systematic review and meta-analysis.
AB  - Studies on the association between single foods or nutrients and colorectal
      cancer have provided inconsistent results. Previous reviews did not conduct a
      quantitative synthesis of the relation with dietary patterns. We conducted a
      systematic review and meta-analysis of studies addressing the association between
      dietary patterns and colorectal cancer. Studies quantifying the association
      between dietary patterns (defined a posteriori) and colorectal cancer were
      identified in PubMed (until 01.08.2010) and through backward and forward citation
      tracking (ISI Web of Science and Scopus). Summary relative risk (RR) estimates
      and 95% confidence intervals (95% CI) were computed for highest versus lowest
      levels of exposure, for colon cancer (CC) and rectal cancer (RC), and for
      proximal and distal CC, by random effects meta-analysis. Heterogeneity was
      quantified using the I(2) statistic. Eight cohort and eight case-control studies
      defining patterns through principal components and factor analyses were included
      in the systematic review. Meta-analyses were conducted for three patterns: (i)
      'drinker,' characterized by high alcohol consumption (CC: RR(combined)=0.96, 95%
      CI: 0.82-1.12, I(2)=0.6%; RC: RR(combined)=0.83, 95% CI: 0.47-1.45, I(2)=65.1%);
      (ii) 'healthy,' characterized by high fruit/vegetables consumption (CC:
      RR(combined)=0.80, 95% CI: 0.70-0.90, I(2)=55.1%; RC: RR(combined)=1.02, 95% CI:
      0.89-1.17, I(2)=10.8%); (iii) 'western,' characterized by high red/processed meat
      consumption (CC: RR(combined)=1.29, 95% CI: 1.13-1.48, I(2)=31.7%; RC:
      RR(combined)=1.13, 95% CI: 0.92-1.39, I(2)=40.6%). Summary estimates for proximal
      and distal CC were similar. The risk of CC was increased with patterns
      characterized by high intake of red and processed meat and decreased with those
      labelled as 'healthy.' No significant associations were observed for RC.

PMID- 21946863
TI  - Influence of prediagnostic recreational physical activity on survival from breast
      cancer.
AB  - Recreational physical activity (RPA) is associated with a reduced risk of
      developing breast cancer, but there is limited research on whether prediagnostic
      RPA influences survival after breast cancer diagnosis or not. We evaluated the
      association between prediagnostic RPA and risk of death in 1508 women with a
      first breast cancer diagnosis during 1996 and 1997 in the population-based Long
      Island Breast Cancer Study Project. A 5-year mortality, through the end of 2002,
      was assessed using the National Death Index (N=196). An in-person interview was
      completed shortly after diagnosis to obtain information on lifetime RPA, which
      was expressed as metabolic equivalent task hours per week (MET-h/week). A lower
      risk of all-cause death was observed for women who engaged in an average of 9 or
      more MET-h/week of RPA from menarche to diagnosis compared with women who did not
      exercise [age-adjusted and BMI adjusted hazard ratio (HR)=0.57; 95% confidence
      interval (CI)=0.39-0.83], an association that was similar when evaluated
      according to menopausal status. Compared with women who did not engage in
      moderate RPA, those who engaged in any moderate intensity lifetime RPA (>0 MET
      h/week) were found to have lower all-cause mortality (HR=0.62; 95% CI=0.46-0.84)
      and breast cancer-specific mortality (HR=0.64; 95% CI=0.43-0.93). Among
      postmenopausal women, RPA that took place after menopause resulted in a decrease
      in overall mortality, whereas no association was observed for RPA which took
      place prior to menopause (for >0 MET-h/week of RPA vs. no RPA, the HR=0.61; 95%
      CI=0.39-0.94 and HR=1.00; 95% CI=0.65-1.54, respectively). This study provides
      support that RPA prior to breast cancer diagnosis improves survival.

PMID- 21946865
TI  - Allyl complexes of scandium: synthesis and structure of neutral, cationic and
      anionic derivatives.
AB  - Neutral, cationic and anionic allyl compounds of scandium contain highly
      fluxional allyl ligands in solution, whilst in the solid state both eta(1)- and
      eta(3)-binding modes are detected.

PMID- 21946866
TI  - Natural killer T cells in lipoprotein metabolism and atherosclerosis.
AB  - Cells of both the innate and adaptive immune system participate in the
      development of atherosclerosis, a chronic inflammatory disorder of medium and
      large arteries. Natural killer T (NKT) cells express surface markers
      characteristic of natural killer cells and conventional T cells and bridge the
      innate and adaptive immune systems. The development and activation of NKT cells
      is dependent upon CD1d, a MHC-class I-type molecule that presents lipids,
      especially glycolipids to the T cell receptors on NKT cells. There are two
      classes of NKT cells; invariant NKT cells that express a semi-invariant T cell
      receptor and variant NKT cells. This review summarises studies in murine models
      in which the effect of the activation, overexpression or deletion of NKT cells or
      only invariant NKT cells on atherosclerosis has been examined.

PMID- 21946867
TI  - Clubfoot in the twentieth century:  where we were and where we may be going in
      the twenty-first century.
AB  - In the twentieth century clubfoot was one of the commonest congenital deformities
      of the musculoskeletal system with an incidence in some races as low as 0.6 and
      in others as high as 6.8 per thousand live births (Polynesia). Males have the
      deformity twice as often as females. In the early 1900s forceful correction of
      the deformity as espoused by Hugh Owen Thomas was in vogue. In the 1930s Joseph
      Hiram Kite, like Hippocrates (400 BC), recommended repeated gentle manipulations
      to achieve a correction. Instead of bandages Kite used serial plaster casts to
      maintain the correction. During the late 1940s Ignatio Ponseti developed his
      technique of correction through the normal arc of the subtalar joint. In a
      clubfoot the soft tissues are more resistant to pressure than the bones. With
      this concept in mind soft tissue procedures were developed in which the capsules
      and ligaments were released surgically. With safer pediatric anesthesia the
      1960s, 1970s, and 1980s saw surgical approaches that were more and more
      aggressive even including a complete subtalar release. The improved imaging
      modalities and computer graphics of the 1980s led to a better understanding of
      the pathoanatomy. Long-term follow-up studies demonstrating malcorrection,
      overcorrection, pain, and stiffness dampened the enthusiasm for very aggressive
      surgery. The main problem with surgery is that clubfoot wounds heal by a patching
      up process called repair. The losses are made good not with the original tissue
      but with a material that is biologically simple, cheap, and handy - connective
      tissue scar! As the century drew to a close there was a major swing of the
      pendulum to the Ponseti method. Surgeons are now learning the limitations of this
      method. Finally, the author tries to imagine what may happen in the future
      prevention, classification, and treatment of clubfoot with all the advances in
      cell biology, molecular biology, biomechanics, biomaterials, surgery, orthotics,
      and evidence-based medicine.

PMID- 21946868
TI  - Adequacy of treatment, bone remodeling, and clinical outcome in pediatric
      supracondylar humeral fractures.
AB  - The aim of this study was to evaluate and compare, both clinically and
      roentgenographically, 62 extension-type supracondylar fractures on the basis of
      the synthesis method and severity of the fracture, with a mean follow-up of 4
      years and 3 months. Range of motion, axial alignment of the elbow, muscle
      strength, and joint stability were estimated and the Mayo Elbow Performance Index
      and the Pediatric Orthopaedic Society of North America Pediatric Outcomes Data
      Collection Instrument questionnaire were used. Furthermore, we took radiographic
      measurements (Baumann's angle, humero-capitellar angle, and lateral rotational
      percentage). According to Flynn criteria, the clinical outcome of all our
      patients was satisfactory. According to the results of the questionnaires, no
      patients has reported any disabling limitation of the elbow function.
      Radiographic study proved a greater capacity of remodeling in the sagittal plane
      compared with the frontal one, irrespective of severity of fracture assessed by
      the Gartland classification. Statistical analysis stressed the validity of
      postoperative Baumann's angle as a predictor of final carrying angle. With regard
      to the synthesis method, the best way to approach Gartland II fractures proved to
      be by closed reduction and percutaneous pinning; the use of a third Kirschner
      wire in the treatment of Gartland III fractures did not lead to a better result.
      To conclude, remodeling positively influenced the clinical outcome, however,
      irrespective of synthesis method and severity of the fracture, we should pay more
      attention to the adequacy of reduction in frontal plane than in the sagittal one,
      for which a greater capacity of remodeling was proved.

PMID- 21946869
TI  - Total hip arthroplasty to treat congenital musculoskeletal abnormalities in the
      juvenile Down Syndrome hip:  review of literature with case.
AB  - Down Syndrome can result in musculoskeletal abnormalities of the hip at an early
      age. Avascular necrosis of the femoral head can occur as a result of slipped
      capital femoral epiphysis causing the patient a great deal of pain, limiting the
      ability to ambulate. Despite the benefits that this patient group can receive
      from the surgery, surgeons may be apprehensive to operate. It is our experience
      that these patients benefit greatly from arthroplasty without complication. In
      this report, we present a total hip replacement to treat avascular necrosis in an
      adolescent and address the concerns that surgeons may have in treating this
      patient population.

PMID- 21946871
TI  - The importance of promoting physical activity for cancer survivorship.

PMID- 21946872
TI  - Peritonsillar abscess.

PMID- 21946873
TI  - Can New Zealand do better in colorectal cancer?

PMID- 21946874
TI  - Peritonsillar infection in Christchurch 2006-2008: epidemiology and microbiology.
AB  - AIM: Peritonsillar infection is a complication of acute tonsillitis. It is common
      and complications can be life-threatening. This study audits all cases of
      peritonsillar infection presenting to our unit between 2006 and 2008 in order to
      determine if the epidemiology, bacteriology and antibiotic sensitivity has
      changed since previous audits in our unit in 1981-1984 and 1990-1992. METHODS:
      Retrospective chart review. RESULTS: 213 patients were admitted acutely with
      peritonsillar infection between January 2006 and December 2008. The average age
      was 29 years with 30.5% patients in the modal age group of 15-19 years. Male to
      female ratio was 1.5:1. 54% presented with their first episode. 39% received
      antibiotics prior to presentation. In two-thirds of cases, the duration of
      admission was less than 24 hours. Culture results were obtained from 69% of
      specimens. Cultures mostly contained mixed anaerobic and aerobic bacteria. The
      most common aerobes were streptococcal species. Organisms were almost uniformly
      sensitive to penicillin. 21% of patients subsequently underwent tonsillectomy,
      usually as a delayed procedure. CONCLUSION: Peritonsillar infection is a common
      complication of tonsillitis and can be life-threatening. The number of cases
      presenting at Christchurch Hospital has increased disproportionate to the
      population increase since the previous audits. Culture results demonstrate a
      preponderance of mixed organisms, which may be pathological. Organisms and their
      sensitivities have not changed since the previous audits. Infection usually
      responds favourably to drainage in combination with penicillin as the first-line
      antimicrobial agent.

PMID- 21946875
TI  - Acute medical admissions for older people from residential care facilities: are
      they appropriate?
AB  - AIM: Acute medical admissions are increasing and potentially avoidable admissions
      (PAA) from residential care facilities (RCF) have been blamed. Estimates for the
      proportion of PAA from RCFs vary enormously in the literature. This study aimed
      to prospectively determine the level of PAA to a New Zealand hospital. METHODS:
      Two cohorts of consecutive acute medical admissions of older (65 years and older)
      people from RCFs were reviewed (one retrospective and one prospective). Discharge
      domicile and survival at 6 months were determined for all patients. PAAs were
      determined by the treating general physician/geriatrician in the prospective
      cohort. RESULTS: Admissions from RCF are a very heterogeneous group with a wide
      range of diagnoses, levels of dependency and outcomes. Most admissions (88%) from
      lower level care (LLC) were appropriate and most returned to their usual RCF on
      discharge. Patients from higher level care (HLC) patients had poorer outcomes
      (5/8 died in the acute hospital and only 1/8 alive at 6 months). Twenty percent
      of all RCF admissions were potentially avoidable and could have been managed in a
      different setting CONCLUSIONS: Most admissions from RCF were appropriate. However
      for a minority of admissions, other models of care within RCFs and community care
      are needed to provide alternative options of care. These may reduce some acute
      hospital admissions.

PMID- 21946876
TI  - Campylobacteriosis rates show age-related static bimodal and seasonality trends.
AB  - AIM: Campylobacteriosis is highly characterised by a strongly seasonal rate of
      incidence. Age is also known to be a risk factor for sporadic campylobacteriosis,
      but little has been done to quantify age-related rates of campylobacteriosis.
      This study investigates age-related incidence across countries and up to 12 years
      of data, as well as differences in seasonality within age groups. METHODS:
      Graphical and statistical analysis of officially collected campylobacteriosis
      reports from three countries available from official websites. RESULTS: For
      Australia, New Zealand and Canada, rates of campylobacteriosis show marked peaks
      at <4 years and 20-29 year age bands. These peaks indicate that stable age
      related factors impact on campylobacteriosis epidemiology in all three countries.
      Seasonality is expressed differently across these age bands, and in years of
      extremes of incidence. CONCLUSION: Campylobacteriosis is highly seasonal, but
      overlying this is a stable age-related pattern of incidence, with two peaks
      approximately 20 years apart. Highest seasonal differences occur with ages
      between the two peaks.

PMID- 21946877
TI  - Auckland City Hospital's ortho-geriatric service: an audit of patients aged over
      65 with fractured neck of femur.
AB  - BACKGROUND: The process of care of older patients with fractured neck of femur at
      Auckland City Hospital has recently changed with selected patients "fast-tracked"
      as soon as possible postoperatively to a specialised Older People's Health (OPH)
      ward. AIMS: The aims of this study were: to evaluate patient characteristics; to
      analyse process of care; to compare outcomes in those "fast-tracked" patients
      with those receiving usual care; and to compare this information with previous
      data from Auckland City Hospital and other centres in New Zealand. METHOD:
      Prospective case record audit of patients with fractured neck of femur aged 65
      years and over admitted under Orthopaedics over a 4-month period. RESULTS: 115
      patients were audited; mean age was 84 years, 77% were female. Inpatient
      mortality was 5%.  Twenty-four percent of patients had surgery within 24 hours of
      admission. Of those who did not have surgery within 24 hours, 39% were awaiting
      operating theatre availability. Median overall length of stay (LOS) was 27 days.
      Eighty-four percent of patients were transferred to Older Peoples Health.
      Considering all patients, 70% of those living at home pre-fracture returned home
      on discharge. However, only 26% of those in Rest Home returned to Rest Home.
      Overall, 35% of patients were discharged to a higher level of care. Forty-four
      percent of the group were able to walk unaided prior to hip fracture, but only 1%
      on discharge. Forty-three patients were "fast-tracked" to Older Peoples Health.
      Their median overall LOS was 23 days compared to 28 days for those receiving
      usual care. This was due to the shorter time in Orthopaedics. Thirty-three
      percent of this group went to a higher level of care on discharge compared to 35%
      in the group that received usual care. CONCLUSIONS: Many patients experience a
      delay to surgery for non-medical reasons. The percentage transferred to Older
      Peoples Health is high. Fast-tracking to Older Peoples Health shortens overall
      length of stay due to fewer days in Orthopaedics. Many patients require a higher
      level of care after hip fracture, particularly if already resident in Rest Home.
      Demographics and inpatient mortality are comparable, but total length of stay is
      longer than similar New Zealand studies due to a longer length of stay in Older
      Peoples Health. Review of previous data from Auckland City Hospital and from
      other New Zealand centres shows significant variability in process of care for
      older patients with hip fracture.

PMID- 21946878
TI  - Prevalent dietary supplement use in older New Zealand men.
AB  - AIMS: Because of a lack of recent data from New Zealand older men, we examined
      dietary supplement use in this demographic. METHODS: We surveyed men aged $gt;40
      years who were participating in a trial of calcium supplementation on bone and
      cardiovascular outcomes. RESULTS: Forty-seven percent reported using at least one
      supplement and 30% of users took more than two different supplements. Amongst
      users, median monthly expenditure on these products was NZ$20 (interquartile
      range: $10-$45). The most common supplements used were vitamins or minerals
      (49%), followed by nutritional oils (22%) (including fish oils, 13%) and
      glucosamine/chondroitin preparations (13%). Supplements were mainly taken for
      reasons of non-specific prophylaxis or health maintenance (58% of reasons),
      although 21% of reasons cited treatment or symptom alleviation for a medical
      condition. Daily requirements for vitamins A, D and E were exceeded, from
      supplement intake alone, by 12%, 10% and 40% of supplement users respectively.
      CONCLUSIONS: Many older New Zealand men spend substantial amounts of money on
      dietary supplements despite uncertain health benefits. Health professionals
      should remain alert to supplement use by their patients, including males.

PMID- 21946879
TI  - Patterns of chronic pain in the New Zealand population.
AB  - AIM: This study describes the prevalence and impact of chronic and recent pain in
      the New Zealand population and the groups most likely to report and use treatment
      for their chronic pain. Results are compared with international estimates.
      METHODS: Data from the 2006/07 New Zealand Health Survey were analysed covering
      chronic pain, sociodemographic characteristics, chronic pain treatment use and
      health related quality of life. Prevalence estimates are presented. Chi-squared
      and logistic regression analyses were used to identify factors most strongly
      associated with chronic pain. RESULTS: One in six (16.9%) New Zealanders reported
      chronic pain. Prevalence increased with age from 8.6% to 28.1%. People in the
      lowest two levels of three economic living standards categories had much higher
      adjusted odds (3.5 and 1.9) of reporting chronic pain than those with high
      economic living standards. Pacific and Asian peoples had much lower odds of
      reporting chronic pain compared with European/Other. Over a third (36%) did not
      use any treatment for their chronic pain while nearly half (48%) used some form
      of medical treatment. People with greater severity of recent pain, women and
      older age groups had much higher odds of using medical treatment for their
      chronic pain. A substantial minority did not report any treatment for their
      chronic pain. Higher numbers of chronic pain sites and greater severity of recent
      pain were associated with much lower scores across all the SF-36 physical and
      mental health domains. CONCLUSIONS: Patterns of chronic pain in the New Zealand
      are similar to those found internationally and indicate that chronic pain
      represents a major health issue in New Zealand.

PMID- 21946880
TI  - Physical activity among cancer survivors: a literature review.
AB  - AIM: Physical activity offers a variety of health benefits to cancer survivors,
      both during and post-treatment. The aim here is to review: the preferences of
      cancer survivors regarding exercise counselling and participation in a physical
      activity programme; adherence rates among cancer survivors to physical activity
      programmes; and predictors of adherence to exercise training. METHODS: Two
      electronic databases, Ovid MEDLINE(R) 1950 to Present with Daily Update and
      SCOPUS, were used to undertake literature searches for studies examining exercise
      preferences of adult cancer survivors, and physical activity programmes for
      adults at any point of the cancer trajectory. RESULTS: Studies suggest that,
      while physical activity levels are low among cancer survivors, most are
      interested in increasing their participation. Preferences and adherence to
      physical activity programmes differ across a range of demographic, medical, and
      behavioural variables, suggesting the importance of tailoring exercise programmes
      to patient-specific and disease-specific needs. CONCLUSIONS: Current evidence
      supports the benefits of physical activity for improving risk factors associated
      with cancer prognosis. Physical activity programmes developed for oncology
      patients and cancer survivors need to take into account the needs of the target
      population in order to optimise adherence, outcomes, and long-term behavioural
      changes in this population.

PMID- 21946881
TI  - Summary of guidance for the management of early bowel cancer.
AB  - Colorectal cancer is an important public health problem and one of the most
      common cancers registered in New Zealand. In 2009 the New Zealand Guidelines
      Group were commissioned to produce and evidence-based summary of current New
      Zealand and international data to inform best practice in the management of
      people with early bowel cancer. A guideline development team was convened,
      representing a range of stakeholder groups who met to discuss and agree on the
      recommendations for a clinical practice guideline. This article summarises the
      guideline methods and reports the recommendations from the Management of Early
      Bowel Cancer guideline, published in 2011.

PMID- 21946882
TI  - Global polio eradication: progress, but determination and vigilance still needed.
AB  - AIM: To review recent events in the international effort to eradicate polio from
      earth and inform readers of recent changes in strategy that have implications for
      New Zealand METHOD: Review of recent literature and publications from World
      Health Organization (WHO). RESULTS: After initial success in eradicating polio
      from Europe, the Western Pacific and the Americas, transmission of wild type
      polio in Nigeria, India, Pakistan and Afghanistan was never interrupted. These
      foci were the source of importations of polio into more than 40 countries,
      including Australia, that were previously polio-free. This has lead to a change
      in strategy by WHO and there are promising indications that polio is coming under
      control in these places. CONCLUSION: Importation of wild-type polio into New
      Zealand are still possible and it essential to maintain awareness amongst
      clinicians that this can happen, high immunisation levels, an effective National
      Poliomyelitis Response Plan for New Zealand, and ongoing surveillance of acute
      flaccid paralysis.

PMID- 21946883
TI  - Quetiapine-associated cardiomyopathy.

PMID- 21946884
TI  - In-situ and lobular, but not as we know it.

PMID- 21946885
TI  - Boutonniere.

PMID- 21946886
TI  - Do senior medical students know enough clinical anatomy?

PMID- 21946887
TI  - Spiriva (Respimat) increases mortality by 52% in patients with COPD: time to take
      action.

PMID- 21946888
TI  - Response to 'lifetime cardiovascular risk' letter.

PMID- 21946889
TI  - Computational investigation of the speciation of uranyl gluconate complexes in
      aqueous solution.
AB  - The geometries, relative energies and spectroscopic properties of a range of D
      gluconate complexes of uranyl(VI) are studied computationally using density
      functional theory. The effect of pH is accommodated by varying the number of
      water and hydroxide ligands accompanying gluconate in the equatorial plane of the
      uranyl unit. For 1 : 1 complexes, the calculated uranyl nu(asym) stretching
      frequency decreases as pH increases, in agreement with previous experimental
      data. Three different gluconate chelating modes are studied. Their relative
      energies are found to be pH dependent, although the energetic differences between
      them are not sufficient to exclude the possibility of multiple speciation. (13)C
      NMR chemical shifts are calculated for the coordinated gluconate in the high pH
      mimics, and show good agreement with experimental data, supporting the
      experimental conclusion that the six-membered chelate ring is favoured at high
      pH. Attempts to improve the description of the aqueous environment via the
      addition of second solvation shell water molecules resulted in significantly
      worse agreement with experiment for nu(asym). The effect of increasing the
      gluconate concentration is modelled by calculating 1 : 2 and 1 : 3 uranyl : D
      gluconate complexes.

PMID- 21946890
TI  - Epidermal growth factor-stimulated human cervical cancer cell growth is
      associated with EGFR and cyclin D1 activation, independent of COX-2 expression
      levels.
AB  - Cervical cancer constitutes the second most common cancer in women. It is evident
      from earlier studies that epidermal growth factor (EGF) is a mitogen, in that it
      mimics the function of estrogen by mediating cross-talk with other oncoproteins.
      Although epidermal growth factor receptor (EGFR) is highly expressed in breast
      and ovarian tumor tissues, its regulation by the exogenous source of its ligand
      EGF in human papillomavirus (HPV)-associated cervical cancer remains unclear. In
      this study, we addressed the question of whether EGF is required for the
      proliferation of HPV-positive cervical cancer cells and what mechanisms are
      involved. To determine this, we conducted a series of studies using HPV-positive
      human cervical cancer cells, CaSki and HeLa, and stimulated the cells with EGF.
      Our findings suggest that 6 h of stimulation with 10 ng/ml of EGF is sufficient
      to induce cell cycle progression associated with a significant increase in DNA
      synthesis, EGFR, COX-2 and cyclin D1 levels. Consistently, cellular localization
      and Western blot analysis for p-EGFR (Try-1045) protein showed an increase after
      EGF stimulation. Using siRNA gene knockdown assays we have shown that cyclin D1
      siRNA has a significant negative effect on EGFR and inhibit cell growth
      independent of COX-2 levels. In summary, our findings reveal that an exogenous
      EGF stimulation may enhance HPV-related cervical cancer cell proliferation by
      activating EGFR and cyclin D1 that is independent of COX-2 levels, suggesting
      that the inhibitors of EGFR and cyclin D1 may be effective against cervical
      cancer cell proliferation.

PMID- 21946891
TI  - The bibliosphere of ancient science (outside of Alexandria) : a preliminary
      survey.

PMID- 21946892
TI  - Diabetes: T2DM-PPARgamma ligands without the adverse effects?

PMID- 21946894
TI  - Bone: fracture risk prediction--beyond BMD assessment.

PMID- 21946893
TI  - Hypothalamic-pituitary-adrenal axis dysfunction in chronic fatigue syndrome.
AB  - The weight of current evidence supports the presence of the following factors
      related to hypothalamic-pituitary-adrenal (HPA) axis dysfunction in patients with
      chronic fatigue syndrome (CFS): mild hypocortisolism; attenuated diurnal
      variation of cortisol; enhanced negative feedback to the HPA axis; and blunted
      HPA axis responsiveness. Furthermore, HPA axis changes seem clinically relevant,
      as they are associated with worse symptoms and/or disability and with poorer
      outcomes to standard treatments for CFS. Regarding etiology, women with CFS are
      more likely to have reduced cortisol levels. Studies published in the past 8
      years provide further support for a multifactorial model in which several factors
      interact to moderate HPA axis changes. In particular, low activity levels,
      depression and early-life stress appear to reduce cortisol levels, whereas the
      use of psychotropic medication can increase cortisol. Addressing these factors
      for example, with cognitive behavioral therapy-can increase cortisol levels and
      is probably the first-line approach for correcting HPA axis dysfunction at
      present, as steroid replacement is not recommended. Given what is now a fairly
      consistent pattern of findings for the type of HPA axis changes found in CFS, we
      recommend that future work focuses on improving our understanding of the cause
      and relevance of these observed changes.

PMID- 21946895
TI  - OPRM1 A118G genotype fails to predict the effectiveness of naltrexone treatment
      for alcohol dependence.
AB  - Given the evidence from retrospective studies indicating that alcohol-dependent
      patients with homozygous or heterozygous A118G variant of the MU-opioid receptor,
      OPRM1, gene have significantly better outcomes when treated with naltrexone; this
      study examined this prospectively in 100 alcohol-dependent participants
      prescribed naltrexone for 12 weeks and offered six sessions of cognitive
      behavioral therapy or intervention. Comparisons were made among OPRM1 genotypic
      groups on several outcome measures. Naltrexone treatment produced significant
      decreases in self-reported and objective indicators of alcohol use and craving
      from baseline (P<0.0001 and 0.017, respectively), particularly during the first 2
      months of treatment, with 68% completing the study. However, there was no
      evidence of a significant association between OPRM1 A118G genotype and treatment
      success on any of the outcome measures. Therefore, while naltrexone was an
      effective treatment for alcohol dependence, the OPRM1 A118G genotype was not a
      predictor of success.

PMID- 21946896
TI  - Two minor NQO1 and NQO2 alleles predict poor response of breast cancer patients
      to adjuvant doxorubicin and cyclophosphamide therapy.
AB  - OBJECTIVE: A SNP in the NQO1 gene has been implicated in the response of patients
      with breast cancer to anthracycline containing regimens. NQO1, and its homologue
      NQO2, share many substrates yet retain distinct functional differences, with NQO2
      being a more permissive molecule for electron accepting substrates. We aimed to
      determine whether functional NQO2 variants are associated with altered response
      to adjuvant doxorubicin and cyclophosphamide therapy, with or without tamoxifen,
      in the treatment of breast cancer. METHODS: Genomic DNA samples from 227 women
      with early breast cancer were genotyped for NQO1 and NQO2 polymorphisms. All
      participants were treated with an AC adjuvant therapy regimen. The functional
      implications of NQO2 polymorphisms were validated in in-vitro ectopic expression
      models. RESULTS: The NQO1 SNP (rs1800566) was associated with a poorer outcome
      and a lower likelihood of having a treatment delay. Patients who had ER and PR
      negative disease and were wild type for both the NQO1 and an NQO2 SNP (rs1143684)
      had 100% 5-year overall survival compared with 88% for carriers of one minor
      allele and 70% for carriers of two or more minor alleles (P=0.018, log rank).
      Carriers of minor alleles of a triallelic NQO2 promoter polymorphism were more
      likely to be withdrawn from tamoxifen therapy prematurely due to intolerance
      (P=0.009, log rank). MCF-7 cells were sensitized to growth inhibition by
      doxorubicin and 4OH tamoxifen, but not cyclophosphamide, by ectopic expression of
      NQO2. CONCLUSION: This study suggests that both NQO1 and NQO2 modulate the
      efficacy of AC therapy and that NQO2 is associated with tamoxifen toxicity.

PMID- 21946898
TI  - Novel CYP3A4 intron 6 single nucleotide polymorphism is associated with
      simvastatin-mediated cholesterol reduction in the Rotterdam Study.
AB  - OBJECTIVES: CYP3A4 is involved in the oxidative metabolism of many drugs and
      xenobiotics including the HMG-CoA reductase inhibitor simvastatin. The objective
      of this study was to investigate whether a new CYP3A4 functional single
      nucleotide polymorphism (SNP) in intron 6 (CYP3A4*22) modifies the effect of
      simvastatin on total cholesterol (TOTc) or LDL cholesterol (LDLc) reduction in a
      population-based cohort study. METHODS: In a total of 80 incident simvastatin
      users, the association between the CYP3A4 intron 6 C>T SNP (rs35599367) and
      reduction in cholesterol levels was analyzed using linear regression analysis and
      adjusting for potential confounding factors. RESULTS: The CYP3A4*22 allele was
      associated with a trend towards a stronger simvastatin lipid-lowering response,
      as reflected by the greater reduction in both TOTc and LDLc levels when compared
      with homozygous wild type. We observed that the CYP3A4*22 allele carriers had an
      increased reduction in TOTc and LDLc: -0.25 mmol/l (95% confidence interval
      [CI(95%)]=[-0.52; 0.01], P=0.058) and -0.29 mmol/l (CI(95%)=[-0.58; 0.01],
      P=0.054) when compared with homozygous CC. When we adjusted the model for
      potential confounding factors, the corresponding reduction in TOTc was -0.31
      mmol/l (CI(95%)=[-0.59;-0.04], P=0.028) and for LDLc -0.34 mmol/l (CI(95%)=[
      0.66; -0.02], P=0.034) greater for CYP3A4*22 allele carriers when compared with
      homozygotes wild type. CONCLUSION: The CYP3A4*22 intron 6 SNP T-variant allele
      was associated with reduced CYP3A4 activity, resulting in a better lipid lowering
      response to simvastatin, when data were adjusted for confounding factors. This
      observation is a step towards the clarification of the reasons of interindividual
      variability in statins response and may potentially lead to improved tailoring of
      simvastatin therapy.

PMID- 21946899
TI  - Acetylator status and N-acetyltransferase 2 gene polymorphisms; phenotype
      genotype correlation with the sulfamethazine test.
AB  - N-acetyltransferase 2 (NAT2) catalyzes the bioactivation and/or detoxification of
      drugs and carcinogens. The aim of this study was to establish the correlation
      between the NAT2 genotype and the acetylating phenotype in a Mexican population
      using sulfamethazine as a probe. From a total of 122 individuals, 73 (59.8%) were
      slow and 49 (40.2%) were fast acetylators. Eleven individuals (9%) had the wild
      type genotype (NAT2*4/NAT2*4). The most frequent genotype was NAT2*4/NAT2*5B
      observed in 20.66% of individuals. In conclusion, our results show that an
      accurate prediction of the acetylation phenotype by genotyping can be achieved in
      around half of the population. Further studies with a larger number of
      individuals are required to establish correlations between phenotype and genotype
      in half of that patients having a genotype combined with slow/rapid alleles.

PMID- 21946897
TI  - Predicting cirrhosis and clinical outcomes in patients with advanced chronic
      hepatitis C with a panel of genetic markers (CRS7).
AB  - OBJECTIVES: Genetic factors may play a role in fibrosis progression in patients
      with chronic hepatitis C (CHC). A cirrhosis risk score (CRS7) with seven single
      nucleotide polymorphisms was previously shown to correlate with cirrhosis in
      patients with CHC. This study aimed to assess the validity of CRS7 as a marker of
      fibrosis progression and cirrhosis and as a predictor of clinical outcomes in
      patients with CHC. METHODS: A total of 938 patients (677 Caucasians, 165 African
      Americans, and 96 Hispanic/Other) in the Hepatitis C Antiviral Long-term
      Treatment against Cirrhosis Trial were studied. CRS7 was categorized a priori as
      high risk (n=440), medium risk (n=310), or low risk (n=188). Patients were
      assessed for four possible outcomes: fibrosis progression, cirrhosis, clinical
      outcomes [decompensation or hepatocellular carcinoma (HCC)], or HCC alone.
      RESULTS: Twenty-nine percent (142/493) developed an increase in fibrosis score by
      greater than or equal to 2 points on follow-up biopsies, 58% had cirrhosis on one
      or more biopsies, 35% developed at least one clinical outcome, and 13% developed
      HCC. CRS7 (trend test) was associated with risk for fibrosis progression (P=0.04)
      with adjusted hazard ratio of 1.27 (95% confidence interval: 1.01-1.58) and with
      cirrhosis (P=0.05) with adjusted odds ratio of 1.19 (1.00-1.41). Rates of HCC and
      clinical outcomes were increased in patients with higher CRS7 scores, but were
      not statistically significant (P=0.12 clinical outcomes, and P=0.07 HCC). A
      single nucleotide polymorphism in AZIN1 was significantly associated with
      fibrosis progression. CONCLUSION: CRS7 was validated as a predictor of fibrosis
      progression and cirrhosis among Hepatitis C Antiviral Long-term Treatment against
      Cirrhosis patients, who all had advanced fibrosis. CRS7 was not predictive of
      clinical outcome.

PMID- 21946900
TI  - Cancer in nursing homes: characteristics and health-related quality of life among
      cognitively intact residents with and without cancer.
AB  - BACKGROUND: Studies are lacking on how cancer influences physical, mental, and
      social functioning beyond comorbidity among older people without cognitive
      impairment in nursing homes (NHs). OBJECTIVE: The objective was to study the
      sociodemographic characteristics and health-related quality of life (HRQOL) among
      NH residents with and without a cancer diagnosis, adjusting for comorbidity.
      METHODS: This was a cross-sectional observation study: 30 NHs; 227 residents 65
      to 102 years old: 60 with cancer and 167 without, at least 6 months' residence.
      All had Clinical Dementia Rating of 0.5 or less and could converse. Health
      related quality of life was measured using the 36-item Short-Form Health Survey
      in face-to-face interviews. Sociodemographic variables and medical diagnoses were
      obtained from records. Possible differences in HRQOL, controlled for age, gender,
      marital status, education, length of stay, and comorbidity, were examined by
      multiple linear regression analyses. RESULTS: The most common cancer diagnoses
      were breast cancer among women (20%) and prostate cancer among men (12%). More
      residents with cancer were married (P = .007), reported more bodily pain (P =
      .17) and scored lower on all other HRQOL subscales, except for role-emotional.
      General health was worse than that of the residents without cancer (P = .04)
      after adjusting for sociodemographic variables but not for comorbidity (P = .06).
      CONCLUSION: Cognitively intact NH residents with cancer reported more pain and
      worse general health but better role limitation related to emotional problems
      compared with residents without cancer. The difference in general health was
      partly due to comorbidity. IMPLICATIONS FOR PRACTICE: Nurses should pay attention
      to HRQOL among NH residents with cancer and especially observe and ensure pain
      treatment.

PMID- 21946901
TI  - Mammography self-efficacy scale and breast cancer fear scale: psychometric
      testing of the Turkish versions.
AB  - BACKGROUND: Self-efficacy for mammography and breast cancer fear are important
      determinants to mammography use. No tools to measure these beliefs of Turkish
      women have been validated. OBJECTIVE: The purpose of this study was to assess the
      psychometric characteristics of the Turkish versions of the Mammography Self
      Efficacy Scale (MSS-T) and the Champion Breast Cancer Fear Scale (CBCFS-T).
      METHODS: Mammography Self-Efficacy Scale and Champion Breast Cancer Fear Scale
      were translated to Turkish language, validated by an expert panel, back
      translated, and tested. Cronbach alpha coefficients and item-total correlations
      were measured to evaluate the reliability of the scales. Exploratory factor
      analysis was used to estimate construct validity of the scales. Independent t
      tests, chi(2) tests, and logistic regression analyses were used to test
      theoretical relationships. RESULTS: Factor analysis yielded 1 factor for MSS-T
      and 2 factors for CBCFS-T with eigenvalues greater than 1. Internal consistency
      values presented acceptable Cronbach alpha levels of .90 for MSS-T and .90 for
      CBCFS-T, and test-retest reliability correlations were 0.56 for MSS-T and 0.60
      for CBCFS-T. CONCLUSIONS: The MSS-T and CBCFS-T demonstrated acceptable
      preliminary values of reliability and validity. Further psychometric testing is
      recommended with women living in different regions of Turkey. IMPLICATIONS FOR
      PRACTICE: The scales can offer insights to nurses and other healthcare
      professionals about mammography self-efficacy beliefs, emotional needs, and
      concerns of Turkish women related to breast cancer fear. The scales may be useful
      as process measures to assess the efficacy of interventions designed to alter
      self-efficacy and fear and subsequently improve the mammography rates.

PMID- 21946902
TI  - The relationship between social support and the level of anxiety, depression, and
      quality of life of Turkish women with gynecologic cancer.
AB  - BACKGROUND: Anxiety and depression are among the most common psychosocial
      problems with gynecologic cancer patients. In this respect, "social support" has
      become a key tool in the patients' coping with the aforementioned risk factors as
      an important contributor to their well-being. OBJECTIVE: The purpose of this
      study was to assess the relationship between social support and the level of
      anxiety, depression, and quality of life of Turkish women with gynecologic
      cancer. METHODS: In a hospital in Turkey, 187 women with a diagnosis of
      gynecologic cancer comprised a convenience sample and completed 4 study
      instruments in a cross-sectional design. RESULTS: Statistically significant
      correlations among type of perceived social support, quality of life, anxiety,
      and depression (P < .001) were found. While high social support was associated
      with increased quality of life, it was also associated with reduced anxiety and
      depression rates. CONCLUSION: Our study showed that the type of perceived social
      support by the patients with cancer had significant effect on depression,
      anxiety, and quality of life. IMPLICATIONS FOR PRACTICE: Social support is a
      powerful tool that can mediate the effects of difficult life stressors and
      decrease the incidence of mood disorders, and, therefore, greater importance
      should be attached to it in the realm of cancer treatment. Supported by the
      collaborative efforts of family members and healthcare professionals, cancer
      patients will more easily cope with the drawbacks of their state.

PMID- 21946904
TI  - Physical activity promotion among oncology nurses.
AB  - BACKGROUND: Oncology nurses may be influential for providing physical activity
      guidance to cancer patients. OBJECTIVE: The purposes of this study were to
      examine physical activity promotion practices of oncology nurses and to explore
      nurses' perceived benefits of physical activity for cancer patients and barriers
      to physical activity promotion. METHODS: Two thousand e-mails were sent by a data
      service company to a random selection of oncology nurses throughout the United
      States with a link to a Web-based survey. To be eligible, nurses had to be
      currently seeing patients. RESULTS: Completed surveys were received from 274
      oncology nurses. Most participants inquired about physical activity on at least
      some office visits (74.9%) and gave physical activity recommendations to 65.7%
      and 66.9% of on-treatment and posttreatment patients. "Lack of time" and that
      "patients are not interested" were the most prominent barriers identified by
      nurses, whereas perceived benefits for patients were rated favorably, with the
      exception of "reducing risk of recurrence." Almost all perceived benefits and
      barriers were correlated with physical activity promotion, with the strongest
      correlates being "unsure what to recommend" and "unsure that physical activity is
      safe." CONCLUSIONS: Although most oncology nurses frequently inquire about
      patient physical activity, they may be less apt to provide recommendations. A
      number of barriers and perceived benefits may influence physical activity
      promotion, especially concerning what to recommend and patient safety.
      IMPLICATIONS FOR PRACTICE: Oncology nurses would benefit from education
      opportunities about the benefits of physical activity for survival outcomes and
      types of physical activity to recommend.

PMID- 21946903
TI  - Perceived control and hot flashes in treatment-seeking breast cancer survivors
      and menopausal women.
AB  - BACKGROUND: Lower perceived control over hot flashes has been linked to fewer
      coping strategies, more catastrophizing, and greater hot flash severity and
      distress in midlife women, yet this important concept has not yet been studied in
      breast cancer survivors. OBJECTIVE: The aim of this study was to explore
      perceived control over hot flashes and hot flashes in breast cancer survivors
      compared with midlife women without cancer. METHODS: Ninety-nine survivors and
      138 midlife women completed questionnaires and a prospective, electronic hot
      flash diary. All data were collected at a baseline assessment before
      randomization in a behavioral intervention study. RESULTS: Both groups had
      moderate perceived control over hot flashes. Control was not significantly
      related to hot flash frequency but was significantly related to hot flash
      severity, bother, and interference in both groups. A significantly stronger
      association between control and hot flash interference was found for survivors
      than for midlife women. Survivors using hot flash treatments perceived less
      control than did survivors not using hot flash treatments, whereas the opposite
      was true in midlife women. CONCLUSIONS: Findings extend our knowledge of
      perceived control over hot flashes in both survivors and midlife women.
      IMPLICATIONS FOR PRACTICE: Findings emphasize the importance of continued
      menopausal symptom assessment and management, support the importance of
      continuing nursing care even for survivors who are already using hot flash
      treatment, and suggest that nursing interventions aimed at improving perceived
      control over hot flashes may be more helpful for survivors than for midlife
      women.

PMID- 21946905
TI  - Relationship between colorectal cancer screening adherence and knowledge among
      vulnerable rural residents of Appalachian Kentucky.
AB  - BACKGROUND: Colorectal cancer (CRC) is 1 of the leading causes of cancer-related
      deaths among residents of rural Appalachia. Rates of guideline-consistent CRC
      screening in Appalachian Kentucky are suboptimal. OBJECTIVE: This study sought to
      determine the relationship between CRC screening knowledge, specifically
      regarding recommended screening intervals, and receipt of screening among
      residents of rural Appalachian Kentucky. METHODS: Residents of Appalachian
      Kentucky (n = 1096) between the ages of 50 and 76 years completed a telephone
      survey including questions on demographics, health history, and knowledge about
      CRC screening between November 20, 2009, and April 22, 2010. RESULTS: Although
      67% of respondents indicated receiving screenings according to guidelines,
      respondents also demonstrated significant knowledge deficiencies about screening
      recommendations. Nearly half of respondents were unable to identify the
      recommended screening frequency for any of the CRC screening modalities. Accuracy
      about the recommended frequency of screening was positively associated with
      screening adherence. CONCLUSIONS: Enhanced educational approaches have the
      potential to increase CRC screening adherence in this population and reduce
      cancer mortality in this underserved region. IMPLICATIONS FOR PRACTICE: Nurses
      play a critical role in patient education, which ultimately may increase
      screening rates. To fulfill this role, nurses should incorporate current
      recommendation about CRC screening into educational sessions. Advanced practices
      nurses in rural settings should also be aware of the increased vulnerability of
      their patient population and develop strategies to enhance awareness about CRC
      and the accompanying screening tests.

PMID- 21946906
TI  - A literature review of suicide in cancer patients.
AB  - BACKGROUND: Cancer survivors have a higher suicide rate than the general
      population. Oncology nurses need to have knowledge and skills in assessing risk
      for suicide in this population. OBJECTIVE: This study aimed to conduct a
      literature review on risk factors for and incidence of suicide in patients with
      cancer and to identify potential screening tools. METHODS: PubMed, CINAHL, and
      PsycINFO databases were searched to identify research articles in peer-reviewed
      journals from 1999 to 2009. The variables under study included suicide rate,
      cancer type, demographic characteristics, and signs and symptoms associated with
      suicide. In addition, articles focused on suicide risk assessment tools were also
      included. RESULTS: Twenty-four articles met the inclusion criteria. As in the
      general population, suicide risk was higher among men with cancer as compared
      with women with cancer. Patients aged 65 years or older with cancer have a higher
      rate of suicide compared with those younger than 65 years, with rates highest
      among men 80 years or older. Specific diagnoses associated with higher suicide
      rates include prostate, lung, pancreatic, and head and neck cancers. The first
      year after diagnosis carries a higher risk for completed suicide. Multiple risk
      assessment tools have been developed and are effective in identifying patients
      with depression or hopelessness, factors associated with higher risk for suicide.
      However, no tools exist that sensitively and specifically predict suicide.
      CONCLUSION: The incidence of suicide in someone with a cancer diagnosis is
      approximately double the incidence of suicide in the general population. Early
      detection of depression in special cancer populations, such as older male
      patients, may help identify those at greatest suicide risk. IMPLICATIONS FOR
      PRACTICE: Oncology nurses should be aware of cancer patients considered at higher
      risk for suicide. Systematic screening for suicidal ideation and behavior may
      identify cancer patients at high risk and facilitate appropriate mental health
      evaluation and treatment.

PMID- 21946907
TI  - Optical mapping of action potentials and calcium transients in the mouse heart.
AB  - The mouse heart is a popular model for cardiovascular studies due to the
      existence of low cost technology for genetic engineering in this species.
      Cardiovascular physiological phenotyping of the mouse heart can be easily done
      using fluorescence imaging employing various probes for transmembrane potential
      (V(m;)), calcium transients (CaT), and other parameters. Excitation-contraction
      coupling is characterized by action potential and intracellular calcium dynamics;
      therefore, it is critically important to map both V(m;) and CaT simultaneously
      from the same location on the heart(1-4).  Simultaneous optical mapping from
      Langendorff perfused mouse hearts has the potential to elucidate mechanisms
      underlying heart failure, arrhythmias, metabolic disease, and other heart
      diseases. Visualization of activation, conduction velocity, action potential
      duration, and other parameters at a myriad of sites cannot be achieved from
      cellular level investigation but is well solved by optical mapping(1,5,6).  In
      this paper we present the instrumentation setup and experimental conditions for
      simultaneous optical mapping of V(m;) and CaT in mouse hearts with high spatio
      temporal resolution using state-of-the-art CMOS imaging technology. Consistent
      optical recordings obtained with this method illustrate that simultaneous optical
      mapping of Langendorff perfused mouse hearts is both feasible and reliable.

PMID- 21946908
TI  - Notch is an essential upstream regulator of NF-kappaB and is relevant for
      survival of Hodgkin and Reed-Sternberg cells.
AB  - A major pathogenetic mechanism in classical Hodgkin lymphoma (cHL) is
      constitutive activation of canonical nuclear factor-kappaB (NF-kappaB) p50/p65
      signaling, controlling lymphoma cell proliferation and survival. Recently, we
      demonstrated that aberrant Notch1 activity is a negative regulator of the B cell
      program in B cell-derived Hodgkin and Reed-Sternberg (HRS) cells. Despite
      abundant evidence for a complex context-dependent cross talk between Notch and NF
      kappaB signaling in hematopoietic cells, it is unknown whether these pathways
      interact in HRS cells. Here, we show that Notch-signaling inhibition in HRS cells
      by the gamma-secretase inhibitor (GSI) XII results in decreased alternative
      p52/RelB NF-kappaB signaling, interfering with processing of the NF-kappaB2 gene
      product p100 into its active form p52. As a result, expression of Notch and NF
      kappaB target genes is reduced, and survival of HRS cells is impaired.
      Stimulation of alternative NF-kappaB signaling in the Hodgkin cell line L540cy by
      activation of the CD30 receptor rescued GSI-mediated loss of cell viability and
      apoptosis induction. Our data reveal that Notch is an essential upstream
      regulator of alternative NF-kappaB signaling and indicate cross talk between both
      the pathways in HRS cells. Therefore, we suggest that targeting the Notch pathway
      is a promising therapeutic option in cHL.

PMID- 21946909
TI  - Correlation of the EPR properties of perchlorotriphenylmethyl radicals and their
      efficiency as DNP polarizers.
AB  - Water soluble perchlorinated trityl (PTM) radicals were found to be effective 95
      GHz DNP (dynamic nuclear polarization) polarizers in ex situ (dissolution) (13)C
      DNP (Gabellieri et al., Angew Chem., Int. Ed. 2010, 49, 3360). The degree of the
      nuclear polarization obtained was reported to be dependent on the position of the
      chlorine substituents on the trityl skeleton. In addition, on the basis of the
      DNP frequency sweeps it was suggested that the (13)C NMR signal enhancement is
      mediated by the Cl nuclei. To understand the DNP mechanism of the PTM radicals we
      have explored the 95 GHz EPR characteristics of these radicals that are relevant
      to their performance as DNP polarizers. The EPR spectra of the radicals revealed
      axially symmetric g-tensors. A comparison of the spectra with the (13)C DNP
      frequency sweeps showed that although the solid effect mechanism is operational
      the DNP frequency sweeps reveal some extra width suggesting that contributions
      from EPR forbidden transitions involving (35,37)Cl nuclear flips are likely. This
      was substantiated experimentally by ELDOR (electron-electron double resonance)
      detected NMR measurements, which map the EPR forbidden transitions, and ELDOR
      experiments that follow the depolarization of the electron spin upon irradiation
      of the forbidden EPR transitions. DFT (density functional theory) calculations
      helped to assign the observed transitions and provided the relevant spin
      Hamiltonian parameters. These results show that the (35,37)Cl hyperfine and
      nuclear quadrupolar interactions cause a considerable nuclear state mixing at 95
      GHz thus facilitating the polarization of the Cl nuclei upon microwave
      irradiation. Overlap of Cl nuclear frequencies and the (13)C Larmor frequency
      further facilitates the polarization of the (13)C nuclei by spin diffusion.
      Calculation of the (13)C DNP frequency sweep based on the Cl nuclear polarization
      showed that it does lead to an increase in the width of the spectra, improving
      the agreement with the experimental sweeps, thus supporting the existence of a
      new heteronuclear assisted DNP mechanism.

PMID- 21946910
TI  - Motivation, goal orientation, coaching, and training habits of women
      ultrarunners.
AB  - Ultrarunners participate in running events that exceed the 26.2-mile marathon
      distance (e.g., 50k, 50-100 miles). Very little research exists on ultrarunners,
      especially women. This study is a descriptive study detailing the motivation,
      goal orientation, demographic characteristics (e.g., age, job demands, family
      structure), training habits (e.g., hours per week of training), and coach
      utilization of women ultrarunners. Participants (N = 344) were recruited via the
      Ultra List serve and 4 popular ultrarunning websites, and they completed a
      questionnaire on motivation, goal orientation, training, and coaching using
      Survey Monkey. General health orientation (mean +/- SD) (4.71 +/- 1.06) and
      psychological coping (4.71 +/- 1.03) were the 2 strongest motivational factors.
      Participants were higher in task orientation (1.38 +/- 0.68) (e.g., finishing the
      race or accomplishing various goals) than ego orientation (3.38 +/- 1.01) (e.g.,
      placing in the top 3 overall or beating an opponent). Women trained an average of
      12.49 h.wk(-1) and spent 64% of their time training alone. Training information
      came from their own experience, blogs, websites, and the Ultra List Serve. Over
      three-fourths of the participants (80%) did not use a coach because of cost and a
      perceived lack of necessity. Women ultrarunners in this study were task oriented,
      internally motivated, health, and financially conscious individuals. With
      additional information about women ultrarunners, coaches will be better prepared
      to work with this population and ultrarunners can improve their performance by
      learning about current participants' practices.

PMID- 21946911
TI  - Benzothiazines in organic synthesis. Synthesis of fluorescent 7-amino-2,1
      benzothiazines.
AB  - Fluorescent 7-amino-2,1-benzothiazines were prepared in high yields using the
      palladium-catalyzed reaction of 4-amino-2-chlorobenzaldehydes with a sulfoximine
      or the reaction of 7-fluoro-2,1-benzothiazines with amines.

PMID- 21946912
TI  - Folate, alcohol, and aldehyde dehydrogenase 2 polymorphism and the risk of oral
      and pharyngeal cancer in Japanese.
AB  - Folate consumption is inversely associated with the risk of oral and pharyngeal
      cancer (OPC) and potentially interacts with alcohol drinking in the risk of OPC.
      Aldehyde dehydrogenase 2 (ALDH2) gene polymorphism is known to interact with
      alcohol consumption. The aim of this study was to investigate potential
      interaction between folate, alcohol drinking, and ALDH2 polymorphism in the risk
      of OPC in a Japanese population. The study group comprised 409 head and neck
      cancer cases and 1227 age-matched and sex-matched noncancer controls; of these,
      251 cases and 759 controls were evaluated for ALDH rs671 polymorphism.
      Associations were assessed by odds ratios and 95% confidence intervals in
      multiple logistic regression models. We observed an inverse association between
      folate consumption and OPC risk. The odds ratio for high folate intake was 0.53
      (95% confidence interval: 0.36-0.77) relative to low intake (P trend=0.003). This
      association was consistent across strata of sex, age, smoking, and ALDH2
      genotypes. Interaction between folate consumption, drinking, and ALDH2 genotype
      was remarkable (three-way interaction, P<0.001). We observed significant
      interaction among folate, drinking, and ALDH2 genotype in the Japanese
      population.

PMID- 21946913
TI  - Neurally triggered breaths reduce trigger delay and improve ventilator response
      times in ventilated infants with bronchiolitis.
AB  - PURPOSE: Neurally adjusted ventilatory assist (NAVA) is a mode of ventilation
      designed to improve patient-ventilator interaction by interpreting a neural
      signal from the diaphragm to trigger a supported breath. We hypothesized that
      neurally triggered breaths would reduce trigger delay, ventilator response times,
      and work of breathing in pediatric patients with bronchiolitis. METHODS: Subjects
      with a clinical diagnosis of bronchiolitis were studied in volume support
      (pneumatic trigger) and NAVA (pneumatic and neural trigger) in a crossover
      design. Airway flow and pressure waveforms were obtained with a pneumotachograph
      and computerized digital recorder and were recorded for 120 s for each
      experiment. RESULTS: Neurally triggered breaths had less trigger delay (ms) (40
      +/- 27 vs. 98 +/- 34; p < 0.001) and reduced ventilator response times (ms) (15
      +/- 7 vs. 36 +/- 25; p < 0.001) compared with pneumatically triggered breaths.
      Neurally triggered breaths had reduced pressure-time product (PTP) area A
      (cmH(2)O * s), the area of the pressure curve from initiation of breath to start
      of ventilator pressurization (0.013 +/- 0.010; p < 0.001), and reduced PTP area B
      (cmH(2)O * s), the area of the pressure curve from start of ventilator
      pressurization to return of baseline pressure (0.008 +/- 0.006 vs. 0.023 +/-
      0.009; p = 0.003). Reduced PTP may indicate decreased work of breathing.
      CONCLUSION: Neurally triggered breaths reduce trigger delay, improve ventilator
      response times, and may decrease work of breathing in children with
      bronchiolitis. Further analysis is required to determine if neurally triggered
      breaths will improve patient-ventilator synchrony.

PMID- 21946915
TI  - Addition of enoxaparin to aspirin for the secondary prevention of placental
      vascular complications in women with severe pre-eclampsia. The pilot randomised
      controlled NOH-PE trial.
AB  - Administration of heparin in the secondary prevention of placental vascular
      complications is still experimental. In women with a previous severe pre
      eclampsia, we investigated the effectiveness of enoxaparin, a low-molecular
      weight heparin, in preventing these complications. Between January 2000 and
      January 2010, 224 women from the NOHA First cohort, with previous severe pre
      eclampsia but no foetal loss during their first pregnancy and negative for
      antiphospholipid antibodies, were randomised to either a prophylactic daily dose
      of enoxaparin starting from the positive pregnancy test (n=112), or no enoxaparin
      (n=112). The primary outcome was a composite of at least one of the following:
      pre-eclampsia, abruptio placentae, birthweight <= 5th percentile, or foetal loss
      after 20 weeks. Enoxaparin was associated with a lower frequency of primary
      outcome: 8.9% (n=10/112) vs. 25 % (28/112), p=0.004, hazard ratio = 0.32, 95%
      confidence interval (0.16-0.66), p=0.002. Enoxaparin was safe, with no obvious
      side-effect, no thrombocytopenia nor major bleeding event excess. This pilot
      study shows that enoxaparin given early during the second pregnancy decreases the
      occurrence of placental vascular complications in women with a previous severe
      pre-eclampsia during their first pregnancy.

PMID- 21946914
TI  - Recombinant human milk fat globule-EGF factor 8 produces dose-dependent benefits
      in sepsis.
AB  - PURPOSE: Animal milk fat globule-EGF factor 8 (MFG-E8) has been shown to be
      beneficial in attenuating the inflammatory response in sepsis. In this study, we
      examined the effect of recombinant human MFG-E8 (rhMFG-E8) in an animal model of
      sepsis in an effort to develop it as a potential therapy against sepsis in
      humans. METHODS: Rats were subjected to sepsis by cecal ligation and puncture
      (CLP), and at 5 h post-CLP, they were given different doses of rhMFG-E8 (20, 40,
      80, 160 MUg/kg BW) in normal saline. At 20 h post-CLP, samples were collected for
      further analysis. A 10-day survival study was also performed. RESULTS: At 20 h
      after CLP, organ injury indicators, serum IL-6 and TNF-alpha, and plasma HMGB-1
      levels were significantly increased as compared to sham-operated animals.
      Treatment with 20 MUg/kg rhMFG-E8 significantly reduced these levels. With higher
      doses, further reductions in AST and ALT (59-62%), creatinine (65-68%), and
      lactate (46-57%), and serum IL-6 and TNF-alpha were obtained. The 160 MUg/kg dose
      produced the greatest reduction in serum TNF-alpha. With treatment with 20 MUg/kg
      rhMFG-E8, HMGB-1 levels decreased by 80%, returning back to sham values. In a 10
      day survival study, vehicle-treated animals produced a 36% survival rate, while
      rhMFG-E8 significantly improved the survival rate to 68-72%. Treatment with
      increasing doses of rhMFG-E8 significantly reduced the number of apoptotic cells
      detected and markedly attenuated the tissue damages observed in the lungs.
      CONCLUSIONS: These data suggest that recombinant human MFG-E8 is beneficial in
      ameliorating sepsis in an animal model of sepsis.

PMID- 21946916
TI  - Electrolyte tuning of electrode potentials: the one electron vs. two electron
      reduction of anthraquinone-2-sulfonate in aqueous media.
AB  - The electrode potentials of quinone redox centres in aqueous solutions can be
      tuned by varying the electrolyte cation identity. The phenomenon is due to the
      ion pairing effect of the tetra-n-butylammonium cation with the semiquinone
      intermediate species.

PMID- 21946917
TI  - CRF2 receptor-deficiency eliminates opiate withdrawal distress without impairing
      stress coping.
AB  - The opiate withdrawal syndrome is a severe stressor that powerfully triggers
      addictive drug intake. However, no treatment yet exists that effectively relieves
      opiate withdrawal distress and spares stress-coping abilities. The corticotropin
      releasing factor (CRF) system mediates the stress response, but its role in
      opiate withdrawal distress and bodily strategies aimed to cope with is unknown.
      CRF-like signaling is transmitted by two receptor pathways, termed CRF(1) and
      CRF(2). Here, we report that CRF(2) receptor-deficient (CRF(2)(-/-)) mice lack
      the dysphoria-like and the anhedonia-like states of opiate withdrawal. Moreover,
      in CRF(2)(-/-) mice opiate withdrawal does not increase the activity of brain
      dynorphin, CRF and periaqueductal gray circuitry, which are major substrates of
      opiate withdrawal distress. Nevertheless, CRF(2) receptor-deficiency does not
      impair brain, neuroendocrine and autonomic stress-coping responses to opiate
      withdrawal. The present findings point to the CRF(2) receptor pathway as a unique
      target to relieve opiate withdrawal distress without impairing stress-coping
      abilities.

PMID- 21946918
TI  - Nifedipine prevents hepatic fibrosis in a non-alcoholic steatohepatitis model
      induced by an L-methionine-and choline-deficient diet.
AB  - Recent reports have shown that nifedipine, a calcium channel blocker, increases
      peroxisome proliferator-activated receptor-gamma (PPARgamma) activity. Since
      PPARgamma agonists, such as pioglitazone and rosiglitazone, are effective in
      reducing non-alcoholic steatohepatitis (NASH) and cirrhosis in animal models, we
      examined the protective effects of nifedipine, as compared with bezafibrate, a
      PPARalpha agonist, in a NASH model induced by an L-methionine- and choline
      deficient (MCD) diet. An MCD diet for 20 weeks changed the color of the rat liver
      to yellow with an irregular surface, whereas the color of the liver in both the
      bezafibrate and nifedipine treatment groups was markedly changed to yellow-brown
      with a smooth surface. Furthermore, nifedipine, as well as bezafibrate,
      significantly prevented liver fibrosis induced by an MCD diet, as assessed by
      Masson's trichrome staining, accompanied by a significant decrease in serum AST.
      Overall, nifedipine treatment resulted in an improvement in NASH, similar to
      bezafibrate, in a rat model. In hypertensive patients with metabolic syndrome,
      nifedipine may provide additional benefits, beyond its blood pressure-lowering
      effects, to prevent NASH and fatty liver disease.

PMID- 21946920
TI  - Chromatin: a haul of new histone modifications.

PMID- 21946921
TI  - Human disease: Huge boost for genetics of cognitive disorders.

PMID- 21946919
TI  - Exome sequencing as a tool for Mendelian disease gene discovery.
AB  - Exome sequencing - the targeted sequencing of the subset of the human genome that
      is protein coding - is a powerful and cost-effective new tool for dissecting the
      genetic basis of diseases and traits that have proved to be intractable to
      conventional gene-discovery strategies. Over the past 2 years, experimental and
      analytical approaches relating to exome sequencing have established a rich
      framework for discovering the genes underlying unsolved Mendelian disorders.
      Additionally, exome sequencing is being adapted to explore the extent to which
      rare alleles explain the heritability of complex diseases and health-related
      traits. These advances also set the stage for applying exome and whole-genome
      sequencing to facilitate clinical diagnosis and personalized disease-risk
      profiling.

PMID- 21946922
TI  - A functional whole blood assay to measure viability of mycobacteria, using
      reporter-gene tagged BCG or M.Tb (BCGlux/M.Tb lux).
AB  - Functional assays have long played a key role in measuring of immunogenicity of a
      given vaccine. This is conventionally expressed as serum bactericidal titers.
      Studies of serum bactericidal titers in response to childhood vaccines have
      enabled us to develop and validate cut-off levels for protective immune responses
      and such cut-offs are in routine use. No such assays have been taken forward into
      the routine assessment of vaccines that induce primarily cell-mediated immunity
      in the form of effector T cell responses, such as TB vaccines. In the animal
      model, the performance of a given vaccine candidate is routinely evaluated in
      standardized bactericidal assays, and all current novel TB-vaccine candidates
      have been subjected to this step in their evaluation prior to phase 1 human
      trials. The assessment of immunogenicity and therefore likelihood of protective
      efficacy of novel anti-TB vaccines should ideally undergo a similar step-wise
      evaluation in the human models now, including measurements in bactericidal
      assays. Bactericidal assays in the context of tuberculosis vaccine research are
      already well established in the animal models, where they are applied to screen
      potentially promising vaccine candidates. Reduction of bacterial load in various
      organs functions as the main read-out of immunogenicity. However, no such assays
      have been incorporated into clinical trials for novel anti-TB vaccines to date.
      Although there is still uncertainty about the exact mechanisms that lead to
      killing of mycobacteria inside human macrophages, the interaction of macrophages
      and T cells with mycobacteria is clearly required. The assay described in this
      paper represents a novel generation of bactericidal assays that enables studies
      of such key cellular components with all other cellular and humoral factors
      present in whole blood without making assumptions about their relative individual
      contribution. The assay described by our group uses small volumes of whole blood
      and has already been employed in studies of adults and children in TB-endemic
      settings. We have shown immunogenicity of the BCG vaccine, increased growth of
      mycobacteria in HIV-positive patients, as well as the effect of anti-retroviral
      therapy and Vitamin D on mycobacterial survival in vitro.  Here we summarise the
      methodology, and present our reproducibility data using this relatively simple,
      low-cost and field-friendly model. Note: Definitions/Abbreviations BCG lux = M.
      bovis BCG, Montreal strain, transformed with shuttle plasmid pSMT1 carrying the
      luxAB genes from Vibrio harveyi, under the control of the mycobacterial GroEL
      (hsp60) promoter. CFU = Colony Forming Unit (a measure of mycobacterial
      viability).

PMID- 21946923
TI  - Environmental effects on vibrational properties of carotenoids: experiments and
      calculations on peridinin.
AB  - Carotenoids are employed in light-harvesting complexes of dinoflagellates with
      the two-fold aim to extend the spectral range of the antenna and to protect it
      from radiation damage. We have studied the effect of the environment on the
      vibrational properties of the carotenoid peridinin in different solvents by means
      of vibrational spectroscopies and QM/MM molecular dynamics simulations. Three
      prototypical solvents were considered: cyclohexane (an apolar/aprotic solvent),
      deuterated acetonitrile (a polar/aprotic solvent) and methanol (a polar/protic
      solvent). Thanks to effective normal mode analysis, we were able to assign the
      experimental Raman and IR bands and to clarify the effect of the solvent on band
      shifts. In the 1500-1650 cm(-1) region, seven vibrational modes of the polyene
      chain were identified and assigned to specific molecular vibrations. In the 1700
      1800 cm(-1) region a strong progressive down-shift of the lactonic carbonyl
      frequency is observed passing from cyclohexane to methanol solutions. This has
      been rationalized here in terms of solvent polarity and solute-solvent hydrogen
      bond interactions. On the basis of our data we propose a classification of non
      equivalent peridinins in the Peridinin-Chlorophyll-Proteins, light-harvesting
      complexes of dinoflagellates.

PMID- 21946924
TI  - Comparison of the effects of two humidifier systems on endotracheal tube
      resistance.
AB  - PURPOSE: To compare the effects of two humidifier systems on endotracheal tube
      (ETT) resistance during mechanical ventilation, either an active heated
      humidifier (HH) or a passive heat and moisture exchanger (HME) was selected using
      current clinical recommendations. METHODS: This was a prospective clinical cohort
      study performed in an intensive care unit. Gas conditioning was performed using
      the HH in 22 patients and the HME in another 22. Patients were matched for
      endotracheal tube diameter, days of mechanical ventilation, simplified acute
      physiology score II (SAPS II), and fluid balance. RESULTS: Used-ETT resistance
      was measured immediately after extubation. Unused-ETT resistance was calculated
      with an identical, clean ETT. No differences were found between the HH and HME
      groups in ETT diameter (7.9 +/- 0.4 vs. 7.9 +/- 0.3 mm; p = 0.98), days of
      mechanical ventilation (11.3 +/- 7.7 vs. 9.5 +/- 4.5; p = 0.34), SAPS II (41.0 +/
      13.6 vs. 42.0 +/- 11.7; p = 0.79), or fluid balance (-2,552 +/- 6,268 vs. -2,579
      +/- 5,422 mL; p = 0.98). ETT resistance increased from intubation to extubation:
      from 6.8 +/- 1.1 to 10.6 +/- 4.3 cmH(2)O L(-1) s(-1) in the HH group, (p < 0.001)
      and from 6.8 +/- 1.1 to 10.2 +/- 3.8 cmH(2)O L(-1) s(-1) in the HME group (p <
      0.001), which is a 53% average increase in resistive load. CONCLUSIONS: We did
      not find differences between the two types of humidifiers in terms of airflow
      resistance during prolonged mechanical ventilation when the devices were selected
      on the basis of individual clinical needs. The increase in resistive load is
      physiologically relevant.

PMID- 21946925
TI  - Beneficial effects of humidified high flow nasal oxygen in critical care
      patients: a prospective pilot study.
AB  - PURPOSE: To evaluate the efficiency, safety and outcome of high flow nasal
      cannula oxygen (HFNC) in ICU patients with acute respiratory failure. METHODS:
      Pilot prospective monocentric study. Thirty-eight patients were included.
      Baseline demographic and clinical data, as well as respiratory variables at
      baseline and various times after HFNC initiation during 48 h, were recorded.
      Arterial blood gases were measured before and after the use of HFNC. Noise and
      discomfort were monitored along with outcome and need for invasive mechanical
      ventilation. RESULTS: HFNC significantly reduced the respiratory rate, heart
      rate, dyspnea score, supraclavicular retraction and thoracoabdominal asynchrony,
      and increased pulse oxymetry. These improvements were observed as early as 15 min
      after the beginning of HFNC for respiratory rate and pulse oxymetry. PaO(2) and
      PaO(2)/FiO(2) increased significantly after 1 h HFNC in comparison with baseline
      (141 +/- 106 vs. 95 +/- 40 mmHg, p = 0.009 and 169 +/- 108 vs. 102 +/- 23, p =
      0.036; respectively). These improvements lasted throughout the study period. HFNC
      was used for a mean duration of 2.8 days and a maximum of 7 days. It was never
      interrupted for intolerance. No nosocomial pneumonia occurred during HFNC. Nine
      patients required secondary invasive mechanical ventilation. Absence of a
      significant decrease in the respiratory rate, lower oxygenation and persistence
      of thoracoabdominal asynchrony after HFNC initiation were early indicators of
      HFNC failure. CONCLUSIONS: HFNC has a beneficial effect on clinical signs and
      oxygenation in ICU patients with acute respiratory failure. These favorable
      results constitute a prerequisite to launching a randomized controlled study to
      investigate whether HFNC reduces intubation in these patients.

PMID- 21946926
TI  - Stability of sildenafil (Revatio(r)) dilutions in dextrose 5%.

PMID- 21946927
TI  - Noninvasive ventilation or continuous positive airway pressure in pulmonary edema
      patients with respiratory acidosis? Look at the bicarbonates.

PMID- 21946928
TI  - Suction catheter tip as an endobronchial foreign body.

PMID- 21946929
TI  - Mobile extracorporeal membrane oxygenation after traumatic freshwater submersion
      using bi-caval dual lumen catheter.

PMID- 21946930
TI  - Exogenous pyruvate accelerates glycolysis and promotes capacitation in human
      spermatozoa.
AB  - BACKGROUND: There has been an ongoing debate in the reproductive field about
      whether mammalian spermatozoa rely on glycolysis, oxidative phosphorylation or
      both for their energy production. Recent studies have proposed that human
      spermatozoa depend mainly on glucose for motility and fertilization but the
      mechanism behind an efficient glycolysis in human spermatozoa is not well
      understood. Here, we demonstrate how human spermatozoa utilize exogenous pyruvate
      to enhance glycolytic ATP production, motility, hyperactivation and capacitation,
      events that are crucial for male fertility. METHODS: Purified human spermatozoa
      from healthy donors were incubated under capacitating conditions (including
      albumin, bicarbonate and glucose) and tested for changes in ATP levels, motility,
      hyperactivation and tyrosine phosphorylation after treatment with pyruvate. The
      experiments were repeated in the presence of sodium cyanide in order to assess
      the contribution from mitochondrial respiration. The metabolism of (13)C labeled
      glucose and pyruvate was traced by a combination of liquid chromatography and
      mass spectrometry. RESULTS: The treatment of human spermatozoa with exogenous
      pyruvate increased intracellular ATP levels, progressive motility and
      hyperactivation by 56, 21 and 130%, respectively. In addition, added pyruvate
      induced a significant increase in tyrosine phosphorylation levels. Blocking of
      the electron transport chain did not markedly affect the results, indicating that
      the mechanism is independent of oxidative phosphorylation. However, the observed
      effects could be counteracted by oxamate, an inhibitor of lactate dehydrogenase
      (LDH). Metabolic tracing experiments revealed that the observed rise in ATP
      concentration resulted from an enhanced glycolytic flux, which was increased by
      more than 50% in the presence of exogenous pyruvate. Moreover, all consumed (13)C
      labeled pyruvate added was converted to lactate rather than oxidized in the
      tricarboxylic acid cycle. CONCLUSIONS: Human spermatozoa seem to rely mainly, if
      not entirely, on glycolysis as the source of ATP fueling the energy-demanding
      processes of motility and capacitation. The efficient glycolysis is dependent on
      exogenous pyruvate, which indirectly feeds the accelerated glycolysis with NAD(+)
      through the LDH-mediated conversion of pyruvate to lactate. Pyruvate is present
      in the human female reproductive tract at concentrations in accordance with our
      results. As seen in other mammals, the motility and fertility of human
      spermatozoa seem to be dictated by the available energy substrates present in the
      conspecific female.

PMID- 21946931
TI  - Molecular recognition probes of solvation thermodynamics in solvent mixtures.
AB  - High-throughput UV-Vis experiments using four molecular recognition-based probes,
      made by the combination of two hydrogen bond acceptors, tri-n-butylphosphine
      oxide and N,N'-bis(2-ethylhexyl)acetamide, and two hydrogen bond donors, 4
      phenylazophenol and 4-nitrophenol, were performed. The association constants for
      the 1 : 1 H-bond interaction involved in each probe system were measured in
      mixtures of a polar and non-polar solvent, di-n-hexyl ether and n-octane,
      respectively. Similar behaviour was observed for all four systems. When the
      concentration of the polar solvent was low, the association constant was
      identical to that observed in pure n-octane. However, once the concentration of
      the polar solvent exceeded a threshold, the association constant decreased
      linearly with the concentration of di-n-hexyl ether. Selective solvation in
      mixtures can be understood based on the competition between the multiple
      competing equilibria in the system. In this case, solvation thermodynamics are
      dominated by competition of the ether for solvation of H-bond donors. For the
      more polar solute, 4-nitrophenol, the selective solvation starts at lower
      concentrations of the polar solvent compared with the less polar solute, 4
      phenylazophenol. Thus the speciation and hence the properties of systems
      containing multiple solutes and multiple solvents can be estimated from the H
      bond properties and the concentrations of the individual functional groups.

PMID- 21946933
TI  - Radiographically undetected coracoid fractures diagnosed by sonography. Report of
      seven cases.
AB  - Coracoid process fractures are rare and can be overlooked on routine radiographs
      due to the anatomical orientation of the CP and superimposition of adjacent bone
      structures. Early fracture detection reduces morbidity and allows for proper
      treatment. Sonography of the shoulder is usually performed for evaluation of peri
      articular soft tissues. To the best of our knowledge, sonographic diagnosis of CP
      fracture has not been reported in the literature. We present a retrospective
      review of seven cases of sonographically detected coracoid fractures which were
      undiagnosed at previous standard radiographs. The US diagnosis was confirmed in
      three subjects, two with CT and in one patient with axillary view radiograph.

PMID- 21946934
TI  - Obtain osteoarthritis related molecular signature genes through regulation
      network.
AB  - Osteoarthritis (OA), also known as degenerative joint disease or osteoarthrosis,
      is the most common form of arthritis. OA occurs when cartilage in the joints
      wears down over time. We used the GSE1919 series to identify potential genes that
      correlated to OA. The aim of our study was to obtain a molecular signature of OA
      through the regulation network based on differentially expressed genes. From the
      result of regulation network construction in OA, a number of transcription
      factors (TFs) and pathways closely related to OA were linked by our method.
      Peroxisome proliferator-activated receptor gamma also arises as hub nodes in our
      transcriptome network and certain TFs containing CEBPD, EGR2 and ETS2 were shown
      to be related to OA by a previous study.

PMID- 21946932
TI  - Current views on the functions of interleukin-17A-producing cells in
      atherosclerosis.
AB  - Multiple components of the immune response are involved in the initiation,
      progression and persistence of atherosclerosis. Interleukin (IL)-17A is produced
      by a broad variety of leukocytes and plays an important role in host defense. IL
      17A is also involved in the pathology of several autoimmune diseases mainly via
      the regulation of chemokine expression and leukocyte migration to the site of
      inflammation. There is an increasing body of evidence indicating an association
      between elevated levels of IL-17A and cardiovascular diseases. Interestingly,
      this IL-17A-dependent response occurs in parallel with the Th1-dominant immune
      response during atherogenesis. To date, the precise role of IL-17A+ cells in
      atherosclerosis is controversial. Several studies have suggested a pro
      atherogenic role of IL-17A via the regulation of aortic macrophage numbers, Th1
      related cytokines and aortic chemokine expression. However, two studies recently
      described anti-inflammatory effects of IL-17A on mouse plaque burden via possible
      regulation of aortic VCAM-1 expression and T cell content. Furthermore, an
      initial study using IL-17A-deficient mice demonstrated that IL-17A affects the
      immune composition and inflammatory phenotype of the aortic wall; however, no
      effects were observed on atherosclerosis. Further studies are necessary to fully
      address the role of IL-17A and other IL-17 family members in atherosclerosis.

PMID- 21946935
TI  - Osteoporosis increases chondrocyte proliferation without a change in apoptosis
      during fracture healing in an ovariectomized rat model.
AB  - Osteoporotic fractures commonly occur in the elderly. Current studies regarding
      cell proliferation and apoptosis during osteoporotic fracture healing are
      limited. In this study, we established an osteoporotic fracture healing model.
      Bone loss and callus formation were monitored with DXA, cell proliferation was
      examined using immunohistochemistry with BrdU monoclonal antibody and apoptotic
      cells were detected using the TUNEL method. Both cell proliferation and apoptosis
      occurred during the entire period of the study. BrdU immunostaining showed a
      decreasing tendency in the process of fracture healing. On days 20 and 30 post
      fracture, the percentage of BrdU-positive cells in ovariectomized rats was
      significantly higher compared to sham-operated rats. TUNEL-positive chondrocytes
      reached a peak on day 20 post-fracture. There was no significant difference
      between the two groups. Our results indicate that osteoporosis markedly delays
      the fracture healing process, mostly due to increased chondrocyte proliferation
      without a change in chondrocyte apoptosis.

PMID- 21946936
TI  - A heterogeneous Pd-Bi/C catalyst in the synthesis of L-lyxose and L-ribose from
      naturally occurring D-sugars.
AB  - A critical step in the synthesis of the rare sugars, L-lyxose and L-ribose, from
      the corresponding D-sugars is the oxidation to the lactone. Instead of
      conventional oxidizing agents like bromine or pyridinium dichromate, it was found
      that a heterogeneous catalyst, Pd-Bi/C, could be used for the direct oxidation
      with molecular oxygen. The composition of the catalyst was optimized and the best
      results were obtained with 5 : 1 atomic ratio of Pd : Bi. The overall yields of
      the five-step procedure to L-ribose and L-lyxose were 47% and 50%, respectively.
      The synthetic procedure is advantageous from the viewpoint of overall yield,
      reduced number of steps, and mild reaction conditions. Furthermore, the
      heterogeneous oxidation catalyst can be easily separated from the reaction
      mixture and reused with no loss of activity.

PMID- 21946937
TI  - The "sliver sign": a specific radiographic sign of acute lateral patellar
      dislocation.
AB  - OBJECTIVE: The objective of this work is to assess the prevalence of the sliver
      sign, defined as an intraarticular linear or curvilinear ossific density, in
      association with knee effusion in patients with acute knee trauma, as a predictor
      of recent lateral patellar dislocation (LPD). MATERIALS AND METHODS: A
      retrospective radiology database search for the term 'patellar dislocation' on
      MRI knee exams performed at our institution over a 7-year period identified 216
      studies. Of these, 142 exams met true positive gold standard diagnostic criteria
      for LPD. Imaging findings of both the retrospectively identified radiographs and
      subsequent MRI were recorded. Accuracy of radiographic interpretation was also
      analyzed. RESULTS: After review by an experienced musculoskeletal radiologist, 27
      patients (19%) with LPD had knee radiographs demonstrating intraarticular osseous
      fragments. The majority of these patients had fragments (22/27, 81%) that were
      linear or curvilinear in configuration. A smaller subset of patients had
      fragments (5/27, 19%) that were rounded or oblong, felt to most likely represent
      sequelae of chronic dislocation. The fragments were identified on the patellar
      view only in eight of 27 patients (30%). These fragments were often initially
      misinterpreted, with the diagnosis explicitly stated in the report in 2/27 cases
      (7%). More often, the fractures were described vaguely (13/27, 48%), interpreted
      incorrectly (6/27, 22%), or missed (6/27, 22%). All 27 patients had moderate or
      large knee joint effusions. CONCLUSIONS: In the setting of acute knee trauma,
      knee radiographs demonstrating a joint effusion and an intraarticular sliver-like
      osseous fragment correlate with recent lateral patellar dislocation. The routine
      trauma knee radiographic series does not include a patellar view but probably
      should, especially in young patients.

PMID- 21946938
TI  - Soft-tissue inflammatory myofibroblastic tumors (IMTs) of the limbs: potential
      and limits of diagnostic imaging.
AB  - OBJECTIVE: The objective of this work was to evaluate the potential of diagnostic
      imaging in the identification, localization, and characterization of soft-tissue
      inflammatory myofibroblastic tumors (IMTs) of limbs with correlation to
      differential diagnosis and therapy. MATERIALS AND METHODS: From a retrospective
      analysis of 324 histologically verified soft-tissue lesions of limbs and
      extremities diagnosed in our institute from January 2002 to July 2010, we
      selected seven cases of histologically proven IMT. These included six males and
      one female, aged between 28 and 81 years (mean age, 57 years). Lesions were
      localized in three cases to the thigh, in two cases to the popliteal space, and
      in the remaining two cases, to the shoulder girdle. All patients were evaluated
      on the basis of US, CT, and MRI. RESULTS: Ultrasound detected the presence of a
      non-homogeneous solid formation in all cases and calcifications in three cases.
      CT showed the presence and type of calcification/ossification and bone reaction.
      On MRI, all cases had low signal intensity on SE T1-weighted sequences and an
      intermediate-low signal intensity on SE and FSE T2-weighted sequences in six of
      them; only one case had an intermediate-high signal intensity on SE and FSE T2
      weighted sequences. Both contrast-enhanced CT and MRI showed precocious
      enhancement in association with multiple peripheral hypertrophic blood vessels.
      CONCLUSIONS: On the basis of integrated imaging data obtained by US, CT, and MRI,
      it is possible to evaluate the lesion extension to provide a loco-regional
      staging, to characterize IMTs, and to allow an optimal therapeutical planning.

PMID- 21946939
TI  - Questions and answers on the use of dabigatran and perspectives on the use of
      other new oral anticoagulants in patients with atrial fibrillation. A consensus
      document of the Italian Federation of Thrombosis Centers (FCSA).
AB  - Dabigatran and other new oral anticoagulants (OAC) represent a step forward in
      stroke prevention in patients with atrial fibrillation (AF). They indeed have
      been shown to be an alternative to vitamin K antagonists (VKAs) without the
      burden of laboratory control. However, these new drugs compete with an effective
      and well-established therapy, thus bringing about a series of questions and
      doubts. In this report members of the board of the Italian Federation of
      Thrombosis Centers (FCSA) answer some questions every clinician might be
      confronted with.

PMID- 21946940
TI  - Fatherhood and the risk of cardiovascular mortality in the NIH-AARP Diet and
      Health Study.
AB  - BACKGROUND: Fertility potential and reproductive fitness may reflect a man's
      future health, given that over one-third of the male human genome is involved in
      reproduction. We sought to determine if offspring number predicts cardiovascular
      death in the US men. METHODS: Using data from the NIH-AARP Diet and Health Study,
      137,903 men (aged 50-71) without prior cardiovascular disease were followed-up
      for an average of 10.2 years. International Classification of Diseases, ninth
      edition, codes were used to establish the cause of death, and multivariable Cox
      proportional hazards modeling was used to estimate the association between
      offspring number and cardiovascular death while accounting for sociodemographic
      and lifestyle characteristics. RESULTS: Almost all (92%) participants had
      fathered at least one child and 50% had three or more offspring. A total of 3082
      men died of cardiovascular causes during follow-up for an age-adjusted incidence
      rate of 2.70 per 1000 person-years. Compared with fathers, after adjusting for
      sociodemographic and lifestyle factors, childless men had a 17% [hazard ratio
      (HR): 1.17; 95% confidence interval (CI): 1.03-1.32] increased risk of death from
      cardiovascular disease contracted in the study period, and this elevated risk
      appeared to extend also to men with only one child. In comparison with fathers of
      five or more children, adjusted relative hazards for cardiovascular mortality of
      this sort were 1.06 (95% CI: 0.92-1.22) for four children, 1.02 (0.90-1.16) for
      three children, 1.02 (0.90-1.16) for two children, 1.11 (0.95-1.30) for one child
      and 1.21 (1.03-1.41) for no children. CONCLUSIONS: Married men who have no
      children have a higher risk of dying from cardiovascular disease contracted after
      the age of 50 than men with two or more children.

PMID- 21946941
TI  - Expression levels of matrix metalloproteinase (MMP)-9 and its specific inhibitor
      TIMP-1, in septic and aseptic arthritis of the knee.
AB  - PURPOSE: In cases of septic knee arthritis, there is excess of matrix
      metalloproteinases (MMPs) over tissue inhibitors of metalloproteinases (TIMPs),
      due to enhanced expression and activation that are induced by bacteria in
      comparison with rheumatic or degenerative arthritis. The aim of this study was to
      explore the expression levels of synovial gelatinase MMP-9 and its specific
      inhibitor TIMP-1 in septic and aseptic arthritis and their potential use as
      additional aids to clinical investigation. METHODS: Gelatin zymography and
      western blot analysis were applied in effusions from knees of the patients with
      septic (SA-10 patients), rheumatic (RA-10 patients) and osteoarthritis (OA-10
      patients). RESULTS: Zymographic analysis revealed that all samples contained
      latent MMP-2 activity, albeit activated MMP-2 appeared in more of the septic than
      aseptic effusions. MMP-9 was not detected in osteoarthritic synovial fluid
      samples. Only trace amounts of MMP-9 activity were detected in 4 of 10 patients
      with RA, whereas higher MMP-9 levels were evident in all samples from SA (P =
      0.0241). In immunoblotting assays, samples from SA showed significantly higher
      levels of MMP-9 compared with samples from RA (P = 0.0052), confirming
      zymographic results. Although no significant difference in TIMP-1 levels was
      observed, the estimated MMP-9/TIMP-1 ratio of septic effusions was significantly
      higher compared with aseptic ones (P = 0.0029). CONCLUSIONS: The data presented
      suggest enhanced expression and activation of MMP-9 in septic native knee
      arthritis compared with aseptic. The presence of high levels of MMP-9 with
      concomitantly increased MMP-9/TIMP-1 ratio and activated gelatinases in
      effusions, independent of neutrophilic counts, may be indicative for infection.

PMID- 21946942
TI  - The 3D analysis of the sagittal curvature of the femoral trochlea in the Chinese
      population.
AB  - PURPOSE: An unnatural design of the sagittal geometry of the femoral trochlea may
      cause abnormal patellofemoral kinematics and complications after knee
      arthroplasty. Most previous studies examined the sagittal curvature of the
      femoral trochlea on 2D parasagittal planes, which may not represent the true
      sagittal curvature of the complex 3D femoral trochlea. METHODS: The current study
      evaluated the sagittal geometry of the femoral trochlea of 100 healthy Chinese
      subjects (50 women and 50 men) with 3D analysis. A close-fit sphere was generated
      on the surface of the medial and lateral trochlear articular surface,
      respectively. The radii of the spheres represented the sagittal radii of the
      femoral trochlear sagittal curvature. A cylinder was then established and its
      radius was adjusted to allow the deepest points of the curved trochlear groove
      touching the cylindrical surface. The radius of the cylinder represented the
      sagittal radius of the trochlear groove. RESULTS: In the men, the average radii
      of the curvature of the femoral trochlea were 18.8 +/- 2.5 mm and 25.5 +/- 2.8 mm
      for the medial and lateral femoral trochleas, respectively. In the women, the
      average radii of the curvature of the femoral trochlea were 20.2 +/- 3.0 mm and
      26.6 +/- 2.7 mm for the medial and lateral femoral trochleas, respectively. The
      average radius of the cylinder of the trochlea groove was 19.6 +/- 2.0 mm with a
      circular arc of 123.2 degrees  +/- 13.0 degrees  in the men. In the women, the
      radius was 20.2 +/- 1.7 mm with a circular arc of 127.9 degrees  +/- 11.7 degrees
      . CONCLUSION: The present study provided a reliable and consistent assessment of
      the sagittal geometry of the femoral trochlea in the Chinese population. The
      results of the current study may be helpful to improve the understanding of the
      knee kinematics and develop the physiological knee prostheses.

PMID- 21946943
TI  - Patellofemoral and tibiofemoral articular cartilage and subchondral bone health
      following arthroscopic partial medial meniscectomy.
AB  - PURPOSE: To examine articular cartilage and subchondral bone changes in
      tibiofemoral and patellofemoral joints following partial medial meniscectomy.
      METHODS: For this cross-sectional study, 158 patients aged 30-55 years, without
      evidence of knee osteoarthritis at arthroscopic partial medial meniscectomy
      (APMM), and 38 controls were recruited. MRI was performed once on the operated
      knee for each subcohort of 3 months, 2 or 4 years post-surgery, and the randomly
      assigned knee of the controls. Cartilage volume, cartilage defects, and bone size
      were assessed using validated methods. RESULTS: Compared with controls, APMM
      patients had more prevalent cartilage defects in medial tibiofemoral (OR = 3.17,
      95%CI 1.24-8.11) and patellofemoral (OR = 13.76, 95%CI 1.52-124.80) compartments,
      and increased medial tibial plateau bone area (B = 143.8, 95%CI 57.4-230.2). Time
      from APMM was positively associated with cartilage defect prevalence in medial
      tibiofemoral (OR = 1.02, 95%CI 1.00-1.03) and patellofemoral (OR = 1.04, 95%CI
      1.01-1.07) compartments, and medial tibial plateau area (B = 2.5, 95%CI 0.8-4.3),
      but negatively associated with lateral tibial cartilage volume (B = -4.9, 95%CI 
      8.4 to -1.5). The association of APMM and time from APMM with patellar cartilage
      defects was independent of tibial cartilage volume. CONCLUSIONS: Partial medial
      meniscectomy is associated with adverse effects on articular cartilage and
      subchondral bone, which are associated with subsequent osteoarthritis, in both
      tibiofemoral and patellofemoral compartments. LEVEL OF EVIDENCE: III.

PMID- 21946944
TI  - Infrasound increases intracellular calcium concentration and induces apoptosis in
      hippocampi of adult rats.
AB  - In the present study, we determined the effect of infrasonic exposure on
      apoptosis and intracellular free Ca2+ ([Ca2+]i) levels in the hippocampus of
      adult rats. Adult rats were randomly divided into the control and infrasound
      exposure groups. For infrasound treatment, animals received infrasonic exposure
      at 90 (8 Hz) or 130 dB (8 Hz) for 2 h per day. Hippocampi were dissected, and
      isolated hippocampal neurons were cultured. The [Ca2+]i levels in hippocampal
      neurons from adult rat brains were determined by Fluo-3/AM staining with a
      confocal microscope system on days 1, 7, 14, 21 and 28 following infrasonic
      exposure. Apoptosis was evaluated by Annexin V-FITC and propidium iodide double
      staining. Positive cells were sorted and analyzed by flow cytometry. Elevated
      [Ca2+]i levels were observed on days 14 and 21 after rats received daily
      treatment with 90 or 130 dB sound pressure level (SPL) infrasonic exposure
      (p<0.01 vs. control). The highest levels of [Ca2+]i were detected in the 130 dB
      SPL infrasonic exposure group. Meanwhile, apoptosis in hippocampal neurons was
      found to increase on day 7 following 90 dB SPL infrasound exposure, and
      significantly increased on day 14. Upon 130 dB infrasound treatment, apoptosis
      was first observed on day 14, whereas the number of apoptotic cells gradually
      decreased thereafter. Additionally, a marked correlation between cell apoptosis
      and [Ca2+]i levels was found on day 14 and 21 following daily treatment with 90
      and 130 dB SPL, respectively. These results demonstrate that a period of
      infrasonic exposure induced apoptosis and upregulated [Ca2+]i levels in
      hippocampal neurons, suggesting that infrasound may cause damage to the central
      nervous system (CNS) through the Ca2+-mediated apoptotic pathway in hippocampal
      neurons.

PMID- 21946946
TI  - Supramolecular chemistry of monochiral naphthalenediimides.
AB  - Three new N-desymmetrised naphthalenediimides (NDIs) are described, each
      containing one chiral and one achiral centre. The ability of such 'monochiral'
      NDIs to self-assemble into hydrogen-bonded helical nanotubes, to act as a
      sergeant in a 'sergeants-and-soldiers' system and to form a hexameric receptor
      for C(70) was examined. Small differences at the achiral centre were found to
      have significant effects on the supramolecular properties of the NDI. All three
      new NDIs form nanotubes that bind C(60), but with different efficiencies, and one
      is a better sergeant than any of the dichiral NDIs investigated to date.

PMID- 21946945
TI  - Radiological findings for hip dysplasia at skeletal maturity. Validation of
      digital and manual measurement techniques.
AB  - OBJECTIVE: To report on intra-observer, inter-observer, and inter-method
      reliability and agreement for radiological measurements used in the diagnosis of
      hip dysplasia at skeletal maturity, as obtained by a manual and a digital
      measurement technique. MATERIALS AND METHODS: Pelvic radiographs from 95
      participants (56 females) in a follow-up hip study of 18- to 19-year-old patients
      were included. Eleven radiological measurements relevant for hip dysplasia
      (Sharp's, Wiberg's, and Ogata's angles; acetabular roof angle of Tonnis; articulo
      trochanteric distance; acetabular depth-width ratio; femoral head extrusion
      index; maximum teardrop width; and the joint space width in three different
      locations) were validated. Three observers measured the radiographs using both a
      digital measurement program and manually in AgfaWeb1000. Inter-method and inter-
      and intra-observer agreement were analyzed using the mean differences between the
      readings/readers, establishing the 95% limits of agreement. We also calculated
      the minimum detectable change and the intra-class correlation coefficient.
      RESULTS: Large variations among different radiological measurements were
      demonstrated. However, the variation was not related to the use of either the
      manual or digital measurement technique. For measurements with greater absolute
      values (Sharp's angle, femoral head extrusion index, and acetabular depth-width
      ratio) the inter- and intra-observer and inter-method agreements were better as
      compared to measurements with lower absolute values (acetabular roof angle,
      teardrop and joint space width). CONCLUSION: The inter- and intra-observer
      variation differs notably across different radiological measurements relevant for
      hip dysplasia at skeletal maturity, a fact that should be taken into account in
      clinical practice. The agreement between the manual and digital methods is good.

PMID- 21946947
TI  - BF061, a novel antiplatelet and antithrombotic agent targeting P2Y12 receptor and
      phosphodiesterase.
AB  - The addition of phosphodiesterase (PDE) inhibitors has been reported to
      potentiate the antithrombotic effects of P2Y12 antagonists without increasing
      bleeding risk. In this study, we report that a potent antiplatelet agent, 2
      ethylthio-6-phenethylaminoadenosine (BF061), inhibits platelet activation and
      thrombosis via P2Y12 antagonism and PDE inhibition. We explored the antiplatelet
      mechanism of BF061 by measuring cAMP, cGMP levels, PDE activity, and the
      interaction between ADP and P2Y12 using atomic force microscopy. The
      antithrombotic effect of BF061 was evaluated in mice using intravital microscopy
      in FeCl3-induced mesenteric and laser-induced cremasteric arterial thrombosis
      models. BF061 robustly inhibited platelet aggregation and ATP release induced by
      multiple platelet agonists via P2Y12 antagonism and PDE inhibition.
      Interestingly, despite being structurally similar to BF061, P2Y12 receptor
      antagonist AR-C69931MX had no effect on human platelet PDE. In FeCl3-induced
      mesenteric arterial thrombosis model, BF061 effectively prevented thrombus
      formation similarly to clopidogrel; it also reduced thrombus volume in laser
      injured cremaster arteriole model. In contrast, BF061 induced dramatically less
      bleeding at an antithrombotic dose compared to clopidogrel. In summary, we
      developed a novel antiplatelet and antithrombotic agent targeting both P2Y12 and
      PDE. Given the prevalence of combined antiplatelet therapy in clinical practice,
      an antiplatelet agent bearing dual activities may have therapeutic advantage as a
      potential antithrombotic drug.

PMID- 21946948
TI  - The sonic hedgehog pathway as a treatment target for extrahepatic biliary tract
      cancer.
AB  - Sonic hedgehog (SHh) signaling is essential for normal development of the human
      gastrointestinal (GI) tract and is reported to be aberrantly activated in GI
      cancers. However, the association between SHh signaling and extrahepatic biliary
      tract cancer is not clearly understood. In this study, we evaluated the
      activities of SHh family proteins and their downstream signals in extrahepatic
      biliary tract cancer. The activity of the SHh pathway was analyzed in established
      human extrahepatic biliary tract cell lines and human cancer tissues using RT-PCR
      and immunohistochemistry. We also evaluated the effects of suppressing the SHh
      pathway with cyclopamine and siRNA. The SHh, Smo and Gli-1 genes were
      overexpressed in extrahepatic biliary tract cancer cell lines and six
      extrahepatic biliary tract cancer tissues compared to the levels in normal
      biliary tract tissues. The degrees of SHh and Gli-1 expression were independent
      of tumor stage and cancer cell differentiation. SHh pathway suppression with
      cyclopamine or siRNA inhibited proliferation of extrahepatic biliary tract cancer
      cell lines. In conclusion, the SHh pathway is highly activated in extrahepatic
      biliary tract cancer and is a potential anticancer drug target.

PMID- 21946949
TI  - Mid-portion Achilles tendinopathy: why painful? An evidence-based philosophy.

PMID- 21946951
TI  - A concise stereoselective synthesis of (-)-erycibelline.
AB  - (-)-Erycibelline, the dihydroxynortropane alkaloid isolated from Erycibe
      elliptilimba Merr. et Chun., was synthesized using a cyclic nitrone as advanced
      intermediate, wherein the key step was the SmI(2)-induced intramolecular
      reductive coupling of cyclic nitrone with aldehyde which resulted in good yield
      and stereoselectivity.

PMID- 21946950
TI  - Expression of chondro-osteogenic BMPs in clinical samples of patellar
      tendinopathy.
AB  - PURPOSE: The pathogenesis of patellar tendinopathy remains unclear. Expression of
      BMP-2/-4/-7 was reported in an ossified failed tendon healing animal model of
      patellar tendinopathy. This study aimed to investigate the expression of these
      chondro-osteogenic BMPs in clinical samples of patellar tendinopathy. METHODS:
      Patellar tendon samples were collected from 16 consecutive patients with patellar
      tendinopathy and 16 consecutive controls undergoing anterior cruciate ligament
      reconstruction with bone-patellar tendon-bone autograft in the authors' hospital
      after getting their consent. The expression of BMP-2/-4/-7 was examined in all
      samples using immunohistochemistry. Ossification observed in two tendinopathy
      samples was characterized by histology, alizarin red S staining, alcian blue
      staining, TRAP staining and immunohistochemical staining of Sox9, osteopontin
      (OPN) and osteocalcin (OCN). RESULTS: Regions of hypo- and hyper-cellularity and
      vascularity, with loss of crimp structure of collagen matrix, were observed in
      patellar tendinopathy samples. Round cells and in some cases, cells with typical
      chondrocyte phenotype were observed. For the ossified tendinopathy samples with
      positive alizarin red S staining, OPN-positive and Sox9-positive chondrocyte-like
      cells in alcian blue-stained extracellular matrix, OCN-positive osteoblast-like
      cells and TRAP-positive multi-nucleated cells were observed around the ossified
      deposits. No expression of BMP-2/-4/-7 was observed in healthy patellar tendons.
      However, the expression of BMP-2/-4/-7 was observed in all patellar tendinopathy
      samples with or without ossification. CONCLUSIONS: Clinical samples of patellar
      tendinopathy showed ectopic expression of BMP-2/-4/-7. This was not evident in
      control samples from healthy patellar tendons. LEVEL OF EVIDENCE: Prognostic
      studies, Level III.

PMID- 21946952
TI  - Comparison of antithrombotic efficacy between edoxaban, a direct factor Xa
      inhibitor, and fondaparinux, an indirect factor Xa inhibitor under low and high
      shear rates.
AB  - Edoxaban is an oral, direct factor Xa (FXa) inhibitor under late-phase clinical
      development. This study compared the antithrombotic efficacy of edoxaban with
      that of an indirect FXa inhibitor, fondaparinux, in in vivo venous and arterial
      thrombosis models and in ex vivo perfusion chamber thrombosis model under low and
      high shear rates in rats. Venous and arterial thrombi were induced by platinum
      wire insertion into the inferior vena cava and by application of FeCl3 to the
      carotid artery, respectively. The perfusion chamber thrombus was formed by blood
      perfusion into a collagen-coated capillary at 150 s-1 (low shear rate) and 1,600
      s-1 (high shear rate). Effective doses of edoxaban that reduced thrombus
      formation by 50% (ED50) in venous and arterial thrombosis models were 0.076 and
      0.093 mg/kg/h, respectively. In contrast, ED50 of fondaparinux in the arterial
      thrombosis model (>10 mg/kg/h) was markedly higher compared to ED50 in the venous
      thrombosis model (0.021 mg/kg/h). In the perfusion chamber thrombosis model, the
      ratio of ED50 under high shear rate (1.13 mg/kg/h) to that under low shear rate
      (0.63 mg/kg/h) for edoxaban was 1.9, whereas that for fondaparinux was more than
      66. While the efficacy of fondaparinux markedly decreased in arterial thrombosis
      and in a high-shear state, edoxaban exerted consistent antithrombotic effects
      regardless of flow conditions. These results suggest that shear rate is a key
      factor in different antithrombotic effects between edoxaban and fondaparinux.

PMID- 21946953
TI  - The posterolateral fluoroscopy-guided injection technique into the posterior
      subtalar joint: description of the procedure and pilot study on patient outcomes.
AB  - OBJECTIVE: To describe a posterolateral fluoroscopy-guided injection technique
      into the posterior subtalar joint and to report patient outcomes 1 month post
      injection. MATERIALS AND METHODS: Twenty-three consecutive adult patients who
      underwent fluoroscopy-guided injection into the posterior subtalar joint using a
      direct posterolateral approach and who returned an outcomes-based postal
      questionnaire after receiving this injection were included. Numerical pain rating
      scale (NRS) data were collected prior to injection. NRS and Patient's Global
      Impression of Change (PGIC) scales were completed 1 day, 1 week, and 1 month
      after injection. The proportion of patients who improved was calculated for each
      time period. Baseline NRS data were compared to each time point using the
      Wilcoxon test to assess differences. Spearman's correlation coefficient was used
      to compare the 20 min NRS score with all follow-up NRS scores. All available
      images were reviewed for the presence of subtalar osteoarthritis (OA). Patient
      charts were reviewed to identify characteristics of patients referred for
      subtalar injections. Risk ratios were calculated comparing presence of OA or
      other abnormalities with improvement. RESULTS: A posterolateral approach for
      fluoroscopy-guided injections into the subtalar joint is described. There was a
      significant reduction in the mean NRS score at all time periods compared to
      baseline (p <= 0.004). One-third of patients (7/21) reported clinically relevant
      improvement at 1 month. CONCLUSIONS: Fluoroscopy-guided puncture of the posterior
      subtalar joint using a posterolateral approach is possible. Clinically
      significant improvement is reported in 33% of patients after 1 month.

PMID- 21946954
TI  - Paraarticular osteochondroma of a cervico-thoracic facet joint presenting as
      myelopathy.

PMID- 21946955
TI  - Biochanin A ameliorates the cytokine secretion profile of lipopolysaccharide
      stimulated macrophages by a PPARgamma-dependent pathway.
AB  - The role of peroxisome proliferator-activated receptors (PPARs) as anti
      inflammatory mediators has been established, and the fact that some isoflavones
      are dual agonists of PPARalpha/gamma indicates the involvement of PPARalpha
      and/or PPARgamma in the anti-inflammatory action of certain isoflavones. However,
      the dependency of isoflavones on PPARs in their anti-inflammatory action has not
      been demonstrated. Here, we report the dependency of an isoflavone biochanin A
      and the independency of another isoflavone genistein in relation to PPARgamma to
      ameliorate the cytokine secretion profile of lipopolysaccharide (LPS)-stimulated
      mouse RAW264.7 macrophages. A total amount of 10 umol/l of biochanin A or
      genistein significantly suppressed the secretion of tumor necrosis factor alpha
      (TNFalpha) and interleukin-6 (IL-6) in LPS-induced RAW264.7 cells, whereas
      another two isoflavones, formononectin and daidzein, only significantly
      suppressed the secretion of IL-6. Their anti-inflammatory efficiencies were not
      in correspondence with their PPARalpha/gamma agonist activities. Inhibition of
      PPARgamma activity by its antagonist GW9662 significantly reversed the anti
      inflammatory effect of biochanin A but not genistein, which demonstrated the
      dependency of biochanin A and the independency of genistein on PPARgamma in their
      anti-inflammatory actions. Meanwhile, the PPARgamma-dependency of biochanin A was
      further confirmed by the result that the suppression of LPS-induced NF-kappaB
      activation by biochanin A was reversed following GW9662 co-treatment. Moreover,
      inhibition of PPARalpha activity by its antagonist MK886 did not significantly
      reverse the anti-inflammatory effects of biochanin A and genistein, indicating
      that their anti-inflammatory properties were PPARalpha-independent.

PMID- 21946957
TI  - Inequities in health and the Marmot Symposia: time for a stocktake.

PMID- 21946956
TI  - A behavior-based circuit model of how outcome expectations organize learned
      behavior in larval Drosophila.
AB  - Drosophila larvae combine a numerically simple brain, a correspondingly moderate
      behavioral complexity, and the availability of a rich toolbox for transgenic
      manipulation. This makes them attractive as a study case when trying to achieve a
      circuit-level understanding of behavior organization. From a series of behavioral
      experiments, we suggest a circuitry of chemosensory processing, odor-tastant
      memory trace formation, and the "decision" process to behaviorally express these
      memory traces--or not. The model incorporates statements about the neuronal
      organization of innate vs. conditioned chemosensory behavior, and the types of
      interaction between olfactory and gustatory pathways during the establishment as
      well as the behavioral expression of odor-tastant memory traces. It in particular
      suggests that innate olfactory behavior is responsive in nature, whereas
      conditioned olfactory behavior is captured better when seen as an action in
      pursuit of its outcome. It incorporates the available neuroanatomical and
      behavioral data and thus should be useful as scaffold for the ongoing
      investigations of the chemo-behavioral system in larval Drosophila.

PMID- 21946958
TI  - Medically assessing refugees who may have been victims of torture.

PMID- 21946959
TI  - Prevalence of victims of torture in the health screening of quota refugees in New
      Zealand during 2007-2008 and implications for follow-up care.
AB  - New Zealand annually accepts approximately 750 quota refugees from around the
      world for resettlement in New Zealand. The humanitarian nature of the quota
      composition consists of those who are determined by the United Nations refugee
      agency to be in high need of immediate protection, a large proportion of medical
      and disability cases, and women and children at risk. Quota refugees arrive in
      group intakes and participate in assessment and orientation for the first 6 weeks
      at the national Mangere Refugee Resettlement Centre in South Auckland. This paper
      describes the findings of screening for refugees with a history of torture during
      2007-2008. There were 144 refugees or 19.2% of the new arrivals found to have
      histories of torture during this period. The implications for future research,
      and follow-up care of people who have survived torture are discussed.

PMID- 21946961
TI  - A cross-sectional study of opinions related to the tobacco industry and their
      association with smoking status amongst 14-15 year old teenagers in New Zealand.
AB  - BACKGROUND: New Zealand has been at the forefront of tobacco control and can
      boast an impressive range of tobacco control intervention. To date, tobacco
      control policy and interventions have directed very little attention to the
      tobacco industry because they concentrate on reducing demand for tobacco. In
      addition, the tobacco industry does not have a bold profile in the mass media.
      Given this low profile of the tobacco industry and the predominance of measures
      to reduce demand we were interested in teenage perceptions of the tobacco
      industry in New Zealand. METHODS: A cross-sectional sample of 31,459 Year 10
      students was obtained in 2006. Attitudes towards the tobacco industry and smoking
      outcomes were analysed using multivariate logistic regression. RESULTS: Thirty
      six percent of students disagreed that tobacco companies are responsible for
      people starting to smoke and 34% agreed that tobacco companies have equal right
      to sell cigarettes as other companies to sell their products. Female, Maori and
      students from low decile schools, who are all more likely to be smoking or have
      tried smoking, were more likely to show greater acceptance of the tobacco
      industry. Intention to smoke was associated with the belief that tobacco industry
      is not responsible for smoking initiation (odds ratio 1.7, p<0.001), and that the
      tobacco industry is legitimate and credible (odds ratio 2.9, p<0.001). Tolerant
      attitudes towards the tobacco industry were strongly associated with intentions
      to smoke and current smoking amongst teenagers.

PMID- 21946960
TI  - The use of the 'rollie' in New Zealand: preference for loose tobacco among an
      ethnically diverse low socioeconomic urban population.
AB  - AIM: To examine the prevalence of and reasons for smoking roll-your-own (RYO)
      cigarettes in a population of South Auckland adults. METHOD: Cross-sectional
      survey of the parents of 2,973 children at four South Auckland Intermediate
      Schools in 2007-2009. RESULT: Just over a quarter (813; 27%) of parents were
      smokers. Most (82%) were Maori or Pacific peoples (47% and 34% respectively) of
      whom 47% smoked only factory-made (FM) and 38% smoked only RYO cigarettes.
      Exclusive RYO smoking was more common among European (53%) than Maori (40%),
      Pacific (38%) and Asian ethnic groups (23%). The most common reasons for
      preferring RYO over FM cigarettes were lower cost (50%), lasting longer (42%),
      and taste (8%). A few chose RYO because they perceived them to be less harmful
      (5%). CONCLUSION: Reducing the cost benefit of RYO should lessen the potential
      use of RYOs as an alternative to quitting. Health education campaigns are needed
      to counter incorrect beliefs surrounding RYO. Such programmes should include
      awareness in schools, churches and Pacific communities.

PMID- 21946962
TI  - Comparison of two modes of delivery of an exercise prescription scheme.
AB  - AIM: Green Prescription (GRx) referrals from health professionals have been shown
      to be effective for increasing the physical activity levels of patients. Little
      is known about which methods of delivering the programme represents the best
      value for money. The purpose of this paper was to compare the cost and outcomes
      of two modes of delivery of a GRx programme. One mode offered phone support
      involving monthly telephone calls over a 3-4 month period to encourage physical
      activity participation. A second mode offered community support via weekly face
      to-face support group meetings in which physical activities were offered.
      METHODS: The evaluation involved staff interviews, patient interviews and
      analysis of GRx records for the 2007 calendar year. RESULTS: There was a large
      rate of drop-out (68%) from GRx referral to registration. For those who
      registered, there was a clear preference for community support, and engagement of
      Maori and Pacific peoples was higher in this mode of delivery. The proportion
      (but not absolute number) of people who successfully completed their mode of
      delivery was higher with phone support. However, participants in community
      support self-reported a significantly greater number of days of exercise per week
      than those in phone support. The total expected cost per person for phone support
      was $102.07 and $108.15 for community support. A greater proportion of
      participants in community support were very satisfied overall with their mode of
      delivery. CONCLUSION: The two modes were comparable in cost and outcomes, though
      there was greater penetration of target ethnic populations in community support.
      Providing a choice of GRx mode of delivery allows participants to choose based on
      their personal and cultural needs.

PMID- 21946963
TI  - Voices of students in competition: Health Science First Year at the University of
      Otago, Dunedin.
AB  - AIM: The experiences and adjustments of students enrolled in Health Science First
      Year (HSFY) at the University of Otago (Dunedin, New Zealand) were explored to
      understand students' response to competition. The paper highlights the
      expressions of past and present HSFY students' impressions of the programme,
      their experiences, coping strategies and the lessons they learned from the
      programme. METHODS: Qualitative data were collected from past (n=15) and present
      (n=20) HSFY students who wanted to pursue medicine. Eight semi-structured
      interview questions were used to answer four research questions that aimed to
      answer the following: students' impressions of HSFY, students' experiences of
      HSFY; students' adjustments to HSFY, and lessons learned from HSFY. The
      interviews were analysed using narrative analysis to gain a greater understanding
      of their experiences and adjustment. RESULTS: The results indicate students
      perceive the programme as demanding and stressful. The highly competitive nature
      of the programme inhibited their engagement and involvement in other aspects of
      university life. Students identified their experiences as successes and
      challenges. In terms of adjustment, students used cognitive restructuring, self
      regulation and social support. Students learned that they need to balance
      academic and social life because spending too much time almost exclusively on
      academics didn't enrich their first year at university. CONCLUSION: The nature of
      the learning environment impacts on students' holistic development. The
      competitive nature of the programme elicited undue stress on students. However,
      they had to employ strategies to help minimise the impact of stress on their
      functioning.

PMID- 21946964
TI  - An investigation into the health benefits of mindfulness-based stress reduction
      (MBSR) for people living with a range of chronic physical illnesses in New
      Zealand.
AB  - AIM: To establish the efficacy of Mindfulness-based Stress Reduction (MBSR) for
      people with chronic health problems in managing symptoms and coping with their
      illness in an Aotearoa/New Zealand context. METHOD: Twenty-nine participants
      completed a wait-list control study. Physical and psychological health and well
      being were measured before, after and 6 months after the 8-week training
      programme using a variety of internationally recognised screening tools. RESULTS:
      Statistically significant improvements were demonstrated in almost all categories
      measured. CONCLUSION: MBSR demonstrated health benefits for chronic illness
      sufferers. An economical and effective adjunctive therapy for decreasing
      morbidity associated with chronic illness in New Zealand, MBSR provides both
      clinicians and patients with an additional option for the better management of
      chronic illness.

PMID- 21946965
TI  - Comorbidity among patients with colon cancer in New Zealand.
AB  - AIMS: To identify patient factors that are associated with a higher risk of
      comorbidity, and to assess the impact of comorbidity on risk of in-hospital
      death, length of stay and 5-year all-cause survival among a large cohort of
      patients with colon cancer in New Zealand. METHODS: Comorbidity data were
      collected from patients who were diagnosed with colon cancer and admitted to
      public hospitals during 1996-2003. The comorbidity measures included all
      conditions listed in the Charlson Comorbidity Index, as well as a predetermined
      list of additional conditions. We examined predictors of higher comorbidity
      scores. We also measured the impact of comorbidity on in-hospital death, length
      of stay and 5-year all-cause survival using logistic, linear and Cox proportional
      hazard regression models to adjust for confounding by sex, age, ethnicity, extent
      of disease and area level deprivation. RESULTS: There were 11,524 patients
      included in the study. 7.5% of females and 10.3% of men had Charlson scores of
      three or more. Higher comorbidity scores were associated with increasing age, and
      were more common among males, Maori and Pacific people, those with unknown extent
      of disease and those living in the most deprived quintile of New Zealand. Those
      with Charlson scores >= 3 had a higher risk of in-hospital death (OR=4.8; 95% CI
      3.5-6.6), longer lengths of hospital stay (0.14 days 95% CI 0.08-0.2) and lower 5
      year survival HR=2.0; 95%CI=1.8-2.3) compared with those with a score of 0.
      CONCLUSION: This study confirms that comorbidity is common among colon cancer
      patients in New Zealand, and has an adverse and independent effect on outcomes
      related to mortality and length of hospital stay.

PMID- 21946966
TI  - What do specialists and GPs think about the introduction of colorectal cancer
      screening? A qualitative study.
AB  - AIM: To explore the views of GPs and specialists on colorectal cancer (CRC)
      screening. METHODS: Qualitative study using semi-structured interviews of 15 GPs
      and 11 specialists investigating views on the proposed introduction of CRC
      screening in New Zealand. RESULTS: Both GPs and specialists in this study, whilst
      agreeing on the overall merit of a population screening programme for CRC in New
      Zealand, argued that there were not sufficient resources to warrant the
      implementation of such a programme. There was also little support, especially by
      the GPs, for the faecal occult blood test, which is likely to be the screening
      test if implemented. CONCLUSIONS: The concerns of GPs and specialists need to be
      addressed if a screening programme for CRC is introduced in New Zealand. GPs
      undoubtedly would have to be the advocates of this programme to their patients
      and therefore they will have to be convinced of the value of this exercise.

PMID- 21946967
TI  - Herpes rugbiorum: a review on scrum pox and rugby player guidelines.
AB  - Sports, especially contact ones, have long been associated with an increased risk
      of contracting a communicable disease. Viral infections, in particular, have had
      an increased attention, due to their adverse effects on athletes' performance. As
      world sport events have now become more organised and diverse, athletes are now
      exposed to a wider range of pathogens. With the upcoming Rugby World Cup in 2011
      taking place in New Zealand, team-doctors should keep a 'careful' eye on
      potential infectious outbreaks and make sure to adhere to guidelines accessed
      through fact sheets.

PMID- 21946968
TI  - Smokefree prisons in New Zealand: maximising the health gain.
AB  - A total smoking ban in prisons comes into effect from July 2011. The ban,
      introduced by the Corrections Minister, Judith Collins, aims to provide a
      healthier environment for prison staff and inmates through the elimination of
      secondhand smoke. Overseas experience has shown that simply banning smoking will
      not necessarily result in prisoners giving up, nor will it result in the
      maintenance of abstinence by those who do stop smoking during incarceration. In
      order to reap maximum health gains from the total smoking ban in prison policy,
      comprehensive cessation support for all inmates needs to be provided to ensure
      that they quit during incarceration and continue to abstain from smoking upon
      release.

PMID- 21946970
TI  - Constriction "Band-Aid" syndrome causing digital ischaemia.
AB  - A case report is presented in which the use of a "Band-Aid" adhesive dressing in
      a child for a trivial finger wound led to the development of full thickness
      necrosis requiring terminalisation of a digit.

PMID- 21946971
TI  - Left main stem stenosis in the unstable patient--forewarned is forearmed.
AB  - Recognition of clinical and electrocardiographic features suggestive of
      significant left main coronary artery disease is important, particularly in
      patients presenting with an acute coronary syndrome. These include hemodynamic
      instability and widespread ST segment depression, which are well known. In
      addition, ST segment elevation in lead aVr, a less recognised finding associated
      with severe left main disease, may be present.

PMID- 21946972
TI  - Medical image. A rare case of brachial artery fibromuscular dysplasia (FMD).

PMID- 21946973
TI  - Once-daily amoxicillin for Group A Streptococcal (GAS) sore throat as the other
      first-line option: a clarification of the NZ sore throat guidelines.

PMID- 21946974
TI  - Plain packaging for tobacco in New Zealand: local evidence and arguments.

PMID- 21946975
TI  - Antipyretic therapy for influenza infection--benefit or harm?

PMID- 21946976
TI  - Comment on Government response to air pollution articles.

PMID- 21946977
TI  - Off-label treatment.

PMID- 21946978
TI  - Teaching of musculoskeletal medicine in New Zealand.

PMID- 21946979
TI  - Keep the focus on contaminated poultry to further curtail New Zealand's
      campylobacteriosis epidemic.

PMID- 21946980
TI  - Functional performance of mobile versus fixed bearing total knee prostheses: a
      randomised controlled trial.
AB  - PURPOSE: The primary goal of this study was to assess the difference in active
      flexion between patients with a mobile versus a fixed bearing, cruciate
      retaining, and total knee arthroplasty. The study was designed as a randomised
      controlled multi-centre trial. METHODS: Participants were assigned to
      interventions by using block-stratified, random allocation. Outcome parameters
      were active flexion, passive flexion, and Knee Society Score (KSS). Outcome
      parameters were assessed preoperatively and at 3, 6, and 12 months
      postoperatively by an independent nurse. RESULTS: Ninety-two patients from one
      centre were included, 46 in each group. Active flexion was comparable for the two
      groups, 99.9 degrees  for the mobile bearing group and 101 degrees  for the fixed
      bearing group with a baseline controlled difference of 1.0 (95% CI -3.9 to 5.8,
      n.s.). The Clinical KSS was comparable between the two bearing groups (Mobile
      90.0 vs. fixed 92.4, n.s.). The functional KSS showed a difference that was
      attributable to the stair climbing subscore, which showed a difference in favour
      of the fixed bearing design between preoperative and 3 months (7.3 point
      difference; 95% CI 2.3-12.5; P = 0.005) as well as 12 months (4.8 point
      difference; 95% CI 0.1-9.6; P = 0.045). CONCLUSIONS: There were no short-term
      differences in active flexion between fixed bearing and mobile bearing total knee
      arthroplasty. LEVEL OF EVIDENCE: I.

PMID- 21946981
TI  - New trends in ACL research.

PMID- 21946982
TI  - Silver-catalysed intramolecular cyclisation of 2-alkynylacetophenones and 3
      acetyl-2-alkynylpyridines in the presence of ammonia.
AB  - Silver-catalysed/microwave-assisted domino reactions of 2-alkynyl-acetophenones
      and 3-acetyl-2-alkynylpyridines in the presence of ammonia are widely described.
      In most cases the reaction give a mixture of the imino- and carbo-cyclisation
      products, with a general preference for the former. A plausible mechanism is
      proposed and the dual activity of silver salts is supported by NMR experiments.

PMID- 21946983
TI  - Prognostic value of metabolic tumor burden on 18F-FDG PET in nonsurgical patients
      with non-small cell lung cancer.
AB  - PURPOSE: The objective of this study was to assess the prognostic value of
      metabolic tumor burden on 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) positron
      emission tomography (PET)/CT measured with metabolic tumor volume (MTV) and total
      lesion glycolysis (TLG), independent of Union Internationale Contra la Cancrum
      (UICC)/American Joint Committee on Cancer (AJCC) tumor, node, and metastasis
      (TNM) stage, in comparison with that of standardized uptake value (SUV) in
      nonsurgical patients with non-small cell lung cancer (NSCLC). METHODS: This study
      retrospectively reviewed 169 consecutive nonsurgical patients (78 men, 91 women,
      median age of 68 years) with newly diagnosed NSCLC who had pretreatment (18)F-FDG
      PET/CT scans. The (18)F-FDG PET/CT scans were performed in accordance with
      National Cancer Institute guidelines. The MTV of whole-body tumor (MTV(WB)), of
      primary tumor (MTV(T)), of nodal metastases (MTV(N)), and of distant metastases
      (MTV(M)); the TLG of whole-body tumor (TLG(WB)), of primary tumor (TLG(T)), of
      nodal metastases (TLG(N)), and of distant metastases (TLG(M)); the SUV(max) of
      whole-body tumor (SUV(maxWB)), of primary tumor (SUV(maxT)), of nodal metastases
      (SUV(maxN)), and of distant metastases (SUV(maxM)) as well as the SUV(mean) of
      whole-body tumor (SUV(meanWB)), of primary tumor (SUV(meanT)), of nodal
      metastases (SUV(meanN)), and of distant metastases (SUV(meanM)) were measured
      with the PETedge tool on a MIMvista workstation with manual adjustment. The
      median follow-up among survivors was 35 months from the PET/CT (range 2-82
      months). Statistical methods included Kaplan-Meier curves, Cox regression, and C
      statistics. RESULTS: There were a total of 139 deaths during follow-up. Median
      overall survival (OS) was 10.9 months [95% confidence interval (CI) 9.0-13.2
      months]. The MTV was statistically associated with OS. The hazard ratios (HR) for
      1 unit increase of ln(MTV(WB)), ?(MTV(T)), ?(MTV(N)), and ?(MTV(M)) before/after
      adjusting for stage were: 1.47/1.43 (p < 0.001/<0.001), 1.06/1.05 (p <
      0.001/<0.001), 1.11/1.10 (p < 0.001/<0.001), and 1.04/1.03 (p = 0.007/0.043),
      respectively. TLG had statistically significant associations with OS with the HRs
      for 1 unit increase in ln(TLG(WB)), ?(TLG(T)), ?(TLG(N)), and ?(TLG(M))
      before/after adjusting for stage being 1.36/1.33 (p < 0.001/<0.001), 1.02/1.02 (p
      = 0.001/0.002), 1.05/1.04 (p < 0.001/<0.001), and 1.02/1.02 (p = 0.003/0.024),
      respectively. The ln(SUV(maxWB)) and ?(SUV(maxN)) were statistically associated
      with OS with the corresponding HRs for a 1 unit increase before/after adjusting
      for stage being 1.46/1.43 (p = 0.013/0.024) and 1.22/1.16 (p = 0.002/0.040). The
      ?(SUV(meanN)) was statistically associated with OS before and after adjusting for
      stage with HRs for a 1 unit increase of 1.32 (p < 0.001) and 1.24 (p = 0.015),
      respectively. The ?(SUV(meanM)) and ?(SUV(maxM)) were statistically associated
      with OS before adjusting for stage with HRs for a 1 unit increase of 1.26 (p =
      0.017) and 1.18 (p = 0.007), respectively, but not after adjusting for stage (p =
      0.127 and 0.056). There was no statistically significant association between OS
      and ?(SUV(maxT)), ln(SUV(meanWB)), or ?(SUV(meanT)). There was low interobserver
      variability among three radiologists with intraclass correlation coefficients
      (ICC) greater than 0.94 for SUV(maxWB), ln(MTV(WB)), and ln(TLG(WB)).
      Interobserver variability was higher for SUV(meanWB) with an ICC of 0.806.
      CONCLUSION: Baseline metabolic tumor burdens at the level of whole-body tumor,
      primary tumor, nodal metastasis, and distant metastasis as measured with MTV and
      TLG on FDG PET are prognostic measures independent of clinical stage with low
      inter-observer variability and may be used to further stratify nonsurgical
      patients with NSCLC. This study also suggests MTV and TLG are better prognostic
      measures than SUV(max) and SUV(mean). These results will need to be validated in
      larger cohorts in a prospective study.

PMID- 21946984
TI  - Fibrin-related markers in patients with septic shock: individual comparison of D
      dimers and fibrin monomers impacts on prognosis.

PMID- 21946985
TI  - Composite cavity fiber laser sensors based on weak feedback.
AB  - A novel composite cavity optical fiber laser (CCFL) sensor, based on weak
      feedback of the optical fiber end face, is proved theoretically and
      experimentally. The application of the vibration measurement based on the CCFL
      sensor is demonstrated to prove its feasibility.

PMID- 21946986
TI  - Improving the measurement performance for a self-mixing interferometry-based
      displacement sensing system.
AB  - Approaches that are, to our knowledge, novel, are proposed in this paper to
      improve the accuracy performance of self-mixing interferometry (SMI) for
      displacement measurement. First, the characteristics associated with signals
      observed in SMI systems are studied, based on which a new procedure is proposed
      for achieving accurate estimation of the laser phase. The studies also revealed
      the reasons for the inherent errors associated with the existing SMI-based
      techniques for displacement measurement. Then, this paper presents a new method
      for estimating the optical feedback level factor (denoted by C) in real time.
      Combining the new algorithms for estimating the laser phase and updating C value,
      the paper finally presents a novel technique for displacement measurement with
      improved accuracy performance in contrast to existing techniques. The proposed
      technique is verified by both simulation and experimental data.

PMID- 21946987
TI  - Polarizability, volume expansion, and stress contributions to the refractive
      index change of Cu+-Na+ ion exchanged waveguides in glass.
AB  - The refractive index of optical waveguides formed by electric field assisted
      Cu(+)-Na(+) ion exchange in two types of glass is measured. Assuming, as in a
      previously published work, that the observed refractive index increase is solely
      due to polarizability changes, the difference in electronic polarizability
      between Cu(+) and Na(+) ions is determined by applying the Lorentz-Lorenz
      equation to the data. In our work, the concentration of exchanged ions, which is
      a necessary input to the Lorentz-Lorenz equation, is determined by combining
      optical data and electrical data obtained during the exchange. Values for the
      electronic polarizability difference are in agreement with that in the
      literature. However, when a correction is made, taking into consideration the
      measured volume expansion and stress in the glass, the calculated electronic
      polarizability difference is shown to increase by 19%.

PMID- 21946988
TI  - Quasi synchronous tuning for grating feedback lasers.
AB  - A general analytical form of the round trip phase shift in grating feedback diode
      lasers is proposed. Using the new form, it is obvious that the round trip phase
      shift can be independent of rotation angle in first order approximation when only
      one restriction condition is met. We call this the quasi synchronous tuning (QST)
      condition. In the QST region, a considerably large mode hopping free tuning range
      can be obtained. An adjustment structure with only one freedom is needed to
      accurately find and locate the quasi synchronous pivot, which is not strictly
      confined on the grating surface and its extension. It means that the external
      cavity diode lasers design can be easier and the laser can be more stable and
      reliable.

PMID- 21946989
TI  - Measurements of laser phase fluctuations induced by atmospheric turbulence over 2
      km and 17.5 km distances.
AB  - A laser heterodyne system was used to measure the phase fluctuations imposed on a
      1.5 MUm wavelength laser beam when double-passed over long atmospheric paths. Two
      distances were used: 2 and 17.5 km. Results are given for intensity
      scintillation, phase fluctuation time series and spectra, and phase structure
      function. The results are found to agree well with theory: the spectrum of phase
      fluctuations follows the 8/3 power law predicted for Kolmogorov turbulence over 3
      orders of magnitude in frequency. The methods reported here could be used to
      investigate large-scale temperature variations in the atmosphere.

PMID- 21946990
TI  - Application of miniature spectrometer in liquid signature analysis technology.
AB  - A spectral liquid signature analyzer system including a miniature fiber-optic
      spectrometer is described in this paper. Through the combination of the spectral
      method and liquid signature analysis technology, the analytical function of the
      liquid signature analyzer will be improved obviously. With this spectral liquid
      signature analyzer system, the physical, chemical, and mechanical characteristics
      of the tested sample can be obtained at the same time. In detail, that is the
      light intensity signal, the equivalent drop volume signal, and the spectroscopic
      data from the miniature spectrometer. And after merging the information data, the
      three-dimensional fingerprint that is unique to the liquid sample is attainable.
      This three-dimensional fingerprint includes the full information we gain from the
      experiment, and it provides visualized differences in various samples. The
      application of spectral analysis makes it possible for further research into the
      chemical compositions of liquid samples and supplies discrimination evidence to
      different liquids. Therefore, the liquid signature analyzer can be used in more
      fields related to liquid.

PMID- 21946991
TI  - Experimental and theoretical study of a laser-diode-pumped passively Q-switched
      intracavity-frequency-doubled Nd:GdVO4/KTP red laser with V:YAG saturable
      absorber.
AB  - A laser-diode-pumped passively Q-switched intracavity-frequency-doubled
      Nd:GdVO4/KTP red laser with V:YAG saturable absorber is realized in a V-type
      resonator. The dependences of the pulse repetition rate, pulse width, single
      pulse energy, and peak power on the incident pump power are measured and
      contrasted. By assuming the intracavity photon density and the initial population
      inversion density to be Gaussian spatial distributions, the space-dependent rate
      equations of this laser are given. The numerical solutions of the rate equations
      are consistent with the experimental results. In order to optimize the described
      system, the variations of the pulse width, peak power, single-pulse energy, and
      laser efficiency with the initial transmission of the saturable absorber and the
      ratio of the laser beam radius to the pump beam radius are also calculated,
      respectively.

PMID- 21946992
TI  - Ultra-high-precision alignment of the elastomerically mounted elements of the
      science camera lenses for the Mars Science Laboratory (MSL) rover.
AB  - Cameras built for space exploration are required to meet stringent environmental
      conditions, such as thermal and dynamic loads for both the optics (camera lens)
      and imaging electronics. On a multitude of spaceborne imaging instruments,
      optical elements are supported in their mounts via an elastomeric bonding
      approach using a room temperature vulcanizing silicone as the bonding agent.
      Employing this integration method, we achieved element-to-element alignment,
      measured as the total indicated runout, using a high-precision contact probe to
      be on the order of half a wavelength of He-Ne laser light, or 0.3 MUm, on the
      Malin Space Science Systems lenses for the Mars Science Laboratory (MSL) cameras.
      This is a higher precision than the current industry state-of-the-art, and it was
      achieved for the very challenging small diameter lens elements. This paper
      describes the design philosophy, implementation, and integration method that
      resulted in achieving this level of precision for interelement alignment. The
      results are based on actual measurements that were made during the process of
      building the MSL rover's science camera lenses, namely Mastcams, the Mars Hand
      Lens Imager, and the Mars Descent Imager. The optical designs of these cameras
      lenses are described in detail in [Opt. Eng.48, 103002 (2009)], while further
      information on the four science cameras can be found at http://www.msss.com.

PMID- 21946993
TI  - Application of generalized grating imaging to pattern projection in three
      dimensional profilometry.
AB  - The theory of generalized grating imaging for a one-dimensional grating is
      applied to a pattern projection system in pattern projection profilometry.
      Contrast of the projected grating image is calculated under various conditions.
      The results help to determine the conditions suitable for obtaining high contrast
      grating images in a large space. Although the gratings required for the
      profilometry are hexagonal, the theory for two-dimensional gratings is
      prohibitively complex. Therefore, the projection system was designed using the
      one-dimensional theory. The projection system using two-dimensional hexagonal
      gratings was constructed and experiments were done with it. The result agrees
      approximately with the theoretical calculations for one-dimensional gratings.
      This suggests that the one-dimensional theory may be used for estimating the
      approximated behavior for hexagonal gratings for use in pattern projection
      profilometry. Some discussions are given for the application of the projection
      system for profiling the mannequin or human body.

PMID- 21946994
TI  - Pinhole detection in steel slab images using Gabor filter and morphological
      features.
AB  - Presently, product inspection for quality control is becoming an important part
      in the steel manufacturing industry. In this paper, we propose a vision-based
      method for detection of pinholes in the surface of scarfed slabs. The pinhole is
      a very tiny defect that is 1-5 mm in diameter. Because the brightness in the
      surface of a scarfed slab is not uniform and the size of a pinhole is small, it
      is difficult to detect pinholes. To overcome the above-mentioned difficulties, we
      propose a new defect detection algorithm using a Gabor filter and morphological
      features. The Gabor filter was used to extract defective candidates. The
      morphological features are used to identify the pinholes among the defective
      candidates. Finally, the experimental results show that the proposed algorithm is
      effective to detect pinholes in the surface of the scarfed slab.

PMID- 21946995
TI  - Stray light correction for diode-array-based spectrometers using a monochromator.
AB  - Photodiode-array-based spectrometers are increasingly being used in a wide
      variety of applications. However, the signal measured by this type of instrument
      often is not what is anticipated by the user and is often subject to
      contamination from stray light. This paper describes an efficient and low-cost
      stray light correction approach based on a relatively simple system using a
      monochromator-based source. The paper further discusses the limitations of using
      a monochromator instead of a laser, as used by previous researchers, and its
      impact on the quality of the stray light correction. The reliability and
      robustness of the stray light correction matrix generated have been studied and
      are also reported.

PMID- 21946996
TI  - Ultrasensitive guided-mode resonance biosensors superimposed with vertical
      sidewall roughness.
AB  - In this paper, we present our investigations of the effects of vertical-sidewall
      roughness (VSR) on guided-mode resonance (GMR) filters made of subwavelength
      grating for applications to ultrasensitive biosensors operated under IR
      illumination. We designed the spectral FWHM of the grating filter to be as narrow
      as possible in order to emphasize the sensitivity and VSR effects. Three types of
      VSR morphologies on the grating-in terms of the correlation length xi and the rms
      of the maximum roughness deviation sigma-were considered and evaluated. Rigorous
      coupled-wave analysis was then implemented to quantify the shifts in the
      reflective resonance peak wavelength value (PWV) of the grating filter. Our
      simulations show that for specific xi values, the PWVs remain constant even if
      sigma becomes as large as 10 nm; this indicates dramatic bandgaplike stripes,
      which are similar to the bandgaps observed in the band diagrams of photonic
      crystals in the xi-sigma diagram that we have proposed in this study. In other
      words, the effects of VSR on the GMR biosensor performance are insignificant when
      xi is located at certain bands; therefore, this type of roughness is highly
      tolerable even if the linewidth of the filter is decreased to only a few tens of
      nanometers.

PMID- 21946997
TI  - Mueller matrix measurements of algae with different shape and size distributions.
AB  - The full Mueller matrix was measured to obtain the polarization state of the
      scattered light for a variety of algae with different shapes, wall compositions,
      sizes, and refractive indices. The experimental setup was a multiple laser
      Mueller matrix ellipsometer, by which measurements were performed for scattering
      angles from 16 degrees  to 160 degrees  sampled at every second degree for
      wavelengths of 473 nm and 532 nm. Previously, the polarization of light scattered
      from microalgae was investigated only for a few species, and the Mueller matrix
      was found to have little variation between the species. In our work a total of 11
      algal species were investigated, representing diatoms, dinoflagellates,
      coccolithophorids, green algae, and a cryptophyte. The selection of species was
      made to obtain high variability in shape, size, cell wall, and refractive index.
      As in previous investigations, very small variations were found between species
      for most of the Mueller matrix elements, but noticeable variations were found for
      M(11), (M(12)+M(21))/2 and (M(33)+M(44))/2.

PMID- 21946998
TI  - Femtosecond laser electronic excitation tagging for quantitative velocity imaging
      in air.
AB  - Time-accurate velocity measurements in unseeded air are made by tagging nitrogen
      with a femtosecond-duration laser pulse and monitoring the displacement of the
      molecules with a time-delayed, fast-gated camera. Centimeter-long lines are
      written through the focal region of a ~1 mJ, 810 nm laser and are produced by
      nonlinear excitation and dissociation of nitrogen. Negligible heating is
      associated with this interaction. The emission arises from recombining nitrogen
      atoms and lasts for tens of microseconds in natural air. It falls into the 560 to
      660 nm spectral region and consists of multiple spectral lines associated with
      first positive nitrogen transitions. The feasibility of this concept is
      demonstrated with lines written across a free jet, yielding instantaneous and
      averaged velocity profiles. The use of high-intensity femtosecond pulses for flow
      tagging allows the accurate determination of velocity profiles with a single
      laser system and camera.

PMID- 21946999
TI  - Alternative method for measuring effective focal length of lenses using the front
      and back surface reflections from a reference plate.
AB  - We present a simple method for measuring the effective focal length without
      determining the location of principle plane of the lens. The method is based on
      the measurement of confocal backreflection axial responses from the front and
      back surfaces of a reference plate with known refractive index and thickness. We
      proved the concept by measuring the effective focal lengths of thin singlet
      lenses and complex microscope objectives. The theoretical limit of measurement
      precision varies depending on the numerical aperture of the lens. This method can
      provide an alternative focal length measurement method for complex lenses or
      lenses that are permanently attached to other structures. Measurement errors were
      analyzed theoretically and improvements in measurement accuracy were discussed.

PMID- 21947000
TI  - Diffractive incremental and absolute coding principle for optical rotary sensors.
AB  - Rotary sensors are an essential component in numerous applications where a
      rotation movement has to be detected. With optical encoders, a high angular
      resolution can be achieved. As a disadvantage, the resolution enhancement is
      associated with increasing cost. To overcome this issue, a coding principle is
      presented that uses a diffractive solid measure on a microstructured plastic
      disc. Like a DVD, this encoder disc can be manufactured in a cost effective
      injection molding process. For this approach, a differential incremental code, as
      well as an absolute code, has been developed.

PMID- 21947001
TI  - Projection-aided videometric method for shape measurement of large-scale bulk
      material stockpile.
AB  - Large-scale stockpiles are a common means for the storage of bulk material and
      their shape measurement is a prerequisite for effective transportation and
      logistics management. This paper proposes a projection-aided videometric method
      that is based on stereo vision and makes use of projections and epipolar geometry
      constraints to solve the correspondence problem. A prototype measuring system was
      developed that can work in real time and achieve measuring accuracy of 0.71 mm in
      terms of the flatness deviation and 0.54 mm in terms of the depth error, as
      proven by the experimental results.

PMID- 21947003
TI  - Ray-tracing method for isotropic inhomogeneous refractive-index media from
      arbitrary discrete input.
AB  - We have developed a ray-tracing simulation procedure for optically isotropic
      gradient refractive-index media. The procedure can take discrete points of
      arbitrary distribution for the definition of refractive-index distributions and
      lens surfaces. It is useful for simulating ray trajectories in real lens systems.
      The procedure is applied to a ray-tracing simulation of the Luneburg lens and a
      radial gradient optical fiber. The simulation results are compared with the
      analytical solutions, and it is shown that they are in precise agreement.

PMID- 21947002
TI  - Blood oxygenation measurements by multichannel reflectometry on the venous and
      arterial structures of the retina.
AB  - The aim of the present study was to propose a model and a method to derive the
      oxyhemoglobin blood content in the retinal veins and arteries by full spectrum
      reflectometry measurements in the spectral zone from 430 to 680 nm. We proposed a
      mathematical equation expressed as a linear combination of two terms
      S(OHb)(lambda) and S(Hb)(lambda) representing the normalized spectral absorption
      functions of the hemoglobin and the oxyhemoglobin, one term lambda(-n)
      representing the ocular media absorption with scattering, and a family of multi
      Gaussian functions, which usefully compensate for the noncompatibility of the
      model and the experimental data in the red spectral zone. The present paper
      suggests that the spectral reflection function in the area from 520 to 580 nm is
      optimal in calculating the oxyhemoglobin concentration of the blood contained in
      the endothelial structures of retinal vessels. The model calculation needs a
      function (1/lambda)(-n) that corrects for the ocular media absorption and light
      scattering on the vessels' structures. For the spectral area of lights with
      wavelength larger than 580 nm, the reflected light represents mainly the light
      scattering on the red blood cells.

PMID- 21947004
TI  - Pointing efficiency in Gaussian beam coherent ladar.
AB  - Random pointing errors in coherent ladar tend to cause a reduction in measured
      signal power due to misalignment among the transmitter, receiver, and (hard)
      target. A simple model for the size of this impact, in terms of the size of the
      pointing error, would be useful in the design and evaluation of coherent ladar
      systems. To be most applicable to monostatic systems, the model should also
      include correlation between transmitter and receiver pointing errors. We derive
      an analytic expression for the reduction in average signal power, which we call
      pointing efficiency, based on Gaussian beam coherent ladar with Gaussian pointing
      errors that includes arbitrary correlation between transmitter and receiver
      pointing errors.

PMID- 21947005
TI  - Dynamics of human adipose lipid turnover in health and metabolic disease.
AB  - Adipose tissue mass is determined by the storage and removal of triglycerides in
      adipocytes. Little is known, however, about adipose lipid turnover in humans in
      health and pathology. To study this in vivo, here we determined lipid age by
      measuring (14)C derived from above ground nuclear bomb tests in adipocyte lipids.
      We report that during the average ten-year lifespan of human adipocytes,
      triglycerides are renewed six times. Lipid age is independent of adipocyte size,
      is very stable across a wide range of adult ages and does not differ between
      genders. Adipocyte lipid turnover, however, is strongly related to conditions
      with disturbed lipid metabolism. In obesity, triglyceride removal rate (lipolysis
      followed by oxidation) is decreased and the amount of triglycerides stored each
      year is increased. In contrast, both lipid removal and storage rates are
      decreased in non-obese patients diagnosed with the most common hereditary form of
      dyslipidaemia, familial combined hyperlipidaemia. Lipid removal rate is
      positively correlated with the capacity of adipocytes to break down
      triglycerides, as assessed through lipolysis, and is inversely related to insulin
      resistance. Our data support a mechanism in which adipocyte lipid storage and
      removal have different roles in health and pathology. High storage but low
      triglyceride removal promotes fat tissue accumulation and obesity. Reduction of
      both triglyceride storage and removal decreases lipid shunting through adipose
      tissue and thus promotes dyslipidaemia. We identify adipocyte lipid turnover as a
      novel target for prevention and treatment of metabolic disease.

PMID- 21947006
TI  - STING is a direct innate immune sensor of cyclic di-GMP.
AB  - The innate immune system detects infection by using germline-encoded receptors
      that are specific for conserved microbial molecules. The recognition of microbial
      ligands leads to the production of cytokines, such as type I interferons (IFNs),
      that are essential for successful pathogen elimination. Cytosolic detection of
      pathogen-derived DNA is one major mechanism of inducing IFN production, and this
      process requires signalling through TANK binding kinase 1 (TBK1) and its
      downstream transcription factor, IFN-regulatory factor 3 (IRF3). In addition, a
      transmembrane protein called STING (stimulator of IFN genes; also known as MITA,
      ERIS, MPYS and TMEM173) functions as an essential signalling adaptor, linking the
      cytosolic detection of DNA to the TBK1-IRF3 signalling axis. Recently, unique
      nucleic acids called cyclic dinucleotides, which function as conserved signalling
      molecules in bacteria, have also been shown to induce a STING-dependent type I
      IFN response. However, a mammalian sensor of cyclic dinucleotides has not been
      identified. Here we report evidence that STING itself is an innate immune sensor
      of cyclic dinucleotides. We demonstrate that STING binds directly to
      radiolabelled cyclic diguanylate monophosphate (c-di-GMP), and we show that
      unlabelled cyclic dinucleotides, but not other nucleotides or nucleic acids,
      compete with c-di-GMP for binding to STING. Furthermore, we identify mutations in
      STING that selectively affect the response to cyclic dinucleotides without
      affecting the response to DNA. Thus, STING seems to function as a direct sensor
      of cyclic dinucleotides, in addition to its established role as a signalling
      adaptor in the IFN response to cytosolic DNA. Cyclic dinucleotides have shown
      promise as novel vaccine adjuvants and immunotherapeutics, and our results
      provide insight into the mechanism by which cyclic dinucleotides are sensed by
      the innate immune system.

PMID- 21947007
TI  - Control of flowering and storage organ formation in potato by FLOWERING LOCUS T.
AB  - Seasonal fluctuations in day length regulate important aspects of plant
      development such as the flowering transition or, in potato (Solanum tuberosum),
      the formation of tubers. Day length is sensed by the leaves, which produce a
      mobile signal transported to the shoot apex or underground stems to induce a
      flowering transition or, respectively, a tuberization transition. Work in
      Arabidopsis, tomato and rice (Oryza sativa) identified the mobile FLOWERING LOCUS
      T (FT) protein as a main component of the long-range 'florigen', or flowering
      hormone, signal. Here we show that expression of the Hd3a gene, the FT orthologue
      in rice, induces strict short-day potato types to tuberize in long days. Tuber
      induction is graft transmissible and the Hd3a-GFP protein is detected in the
      stolons of grafted plants, transport of the fusion protein thus correlating with
      tuber formation. We provide evidence showing that the potato floral and
      tuberization transitions are controlled by two different FT-like paralogues
      (StSP3D and StSP6A) that respond to independent environmental cues, and show that
      an autorelay mechanism involving CONSTANS modulates expression of the
      tuberization-control StSP6A gene.

PMID- 21947008
TI  - Structural basis of RNA recognition and activation by innate immune receptor RIG
      I.
AB  - Retinoic-acid-inducible gene-I (RIG-I; also known as DDX58) is a cytoplasmic
      pathogen recognition receptor that recognizes pathogen-associated molecular
      pattern (PAMP) motifs to differentiate between viral and cellular RNAs. RIG-I is
      activated by blunt-ended double-stranded (ds)RNA with or without a 5'
      triphosphate (ppp), by single-stranded RNA marked by a 5'-ppp and by polyuridine
      sequences. Upon binding to such PAMP motifs, RIG-I initiates a signalling cascade
      that induces innate immune defences and inflammatory cytokines to establish an
      antiviral state. The RIG-I pathway is highly regulated and aberrant signalling
      leads to apoptosis, altered cell differentiation, inflammation, autoimmune
      diseases and cancer. The helicase and repressor domains (RD) of RIG-I recognize
      dsRNA and 5'-ppp RNA to activate the two amino-terminal caspase recruitment
      domains (CARDs) for signalling. Here, to understand the synergy between the
      helicase and the RD for RNA binding, and the contribution of ATP hydrolysis to
      RIG-I activation, we determined the structure of human RIG-I helicase-RD in
      complex with dsRNA and an ATP analogue. The helicase-RD organizes into a ring
      around dsRNA, capping one end, while contacting both strands using previously
      uncharacterized motifs to recognize dsRNA. Small-angle X-ray scattering, limited
      proteolysis and differential scanning fluorimetry indicate that RIG-I is in an
      extended and flexible conformation that compacts upon binding RNA. These results
      provide a detailed view of the role of helicase in dsRNA recognition, the synergy
      between the RD and the helicase for RNA binding and the organization of full
      length RIG-I bound to dsRNA, and provide evidence of a conformational change upon
      RNA binding. The RIG-I helicase-RD structure is consistent with dsRNA
      translocation without unwinding and cooperative binding to RNA. The structure
      yields unprecedented insight into innate immunity and has a broader impact on
      other areas of biology, including RNA interference and DNA repair, which utilize
      homologous helicase domains within DICER and FANCM.

PMID- 21947009
TI  - Structure of human mitochondrial RNA polymerase.
AB  - Transcription of the mitochondrial genome is performed by a single-subunit RNA
      polymerase (mtRNAP) that is distantly related to the RNAP of bacteriophage T7,
      the pol I family of DNA polymerases, and single-subunit RNAPs from chloroplasts.
      Whereas T7 RNAP can initiate transcription by itself, mtRNAP requires the factors
      TFAM and TFB2M for binding and melting promoter DNA. TFAM is an abundant protein
      that binds and bends promoter DNA 15-40 base pairs upstream of the transcription
      start site, and stimulates the recruitment of mtRNAP and TFB2M to the promoter.
      TFB2M assists mtRNAP in promoter melting and reaches the active site of mtRNAP to
      interact with the first base pair of the RNA-DNA hybrid. Here we report the X-ray
      structure of human mtRNAP at 2.5 A resolution, which reveals a T7-like catalytic
      carboxy-terminal domain, an amino-terminal domain that remotely resembles the T7
      promoter-binding domain, a novel pentatricopeptide repeat domain, and a flexible
      N-terminal extension. The pentatricopeptide repeat domain sequesters an AT-rich
      recognition loop, which binds promoter DNA in T7 RNAP, probably explaining the
      need for TFAM during promoter binding. Consistent with this, substitution of a
      conserved arginine residue in the AT-rich recognition loop, or release of this
      loop by deletion of the N-terminal part of mtRNAP, had no effect on
      transcription. The fingers domain and the intercalating hairpin, which melts DNA
      in phage RNAPs, are repositioned, explaining the need for TFB2M during promoter
      melting. Our results provide a new venue for the mechanistic analysis of
      mitochondrial transcription. They also indicate how an early phage-like mtRNAP
      lost functions in promoter binding and melting, which were provided by initiation
      factors in trans during evolution, to enable mitochondrial gene regulation and
      the adaptation of mitochondrial function to changes in the environment.

PMID- 21947010
TI  - Electrochemical plasmonic sensors.
AB  - The enormous progress of nanotechnology during the last decade has made it
      possible to fabricate a great variety of nanostructures. On the nanoscale, metals
      exhibit special electrical and optical properties, which can be utilized for
      novel applications. In particular, plasmonic sensors including both the
      established technique of surface plasmon resonance and more recent nanoplasmonic
      sensors, have recently attracted much attention. However, some of the simplest
      and most successful sensors, such as the glucose biosensor, are based on
      electrical readout. In this review we describe the implementation of
      electrochemistry with plasmonic nanostructures for combined electrical and
      optical signal transduction. We highlight results from different types of
      metallic nanostructures such as nanoparticles, nanowires, nanoholes or simply
      films of nanoscale thickness. We briefly give an overview of their optical
      properties and discuss implementation of electrochemical methods. In particular,
      we review studies on how electrochemical potentials influence the plasmon
      resonances in different nanostructures, as this type of fundamental understanding
      is necessary for successful combination of the methods. Although several combined
      platforms exist, many are not yet in use as sensors partly because of the
      complicated effects from electrochemical potentials on plasmon resonances. Yet,
      there are clearly promising aspects of these sensor combinations and we conclude
      this review by discussing the advantages of synchronized electrical and optical
      readout, illustrating the versatility of these technologies.

PMID- 21947011
TI  - New insights on proteomics of transgenic soybean seeds: evaluation of
      differential expressions of enzymes and proteins.
AB  - This work reports the evaluation of differentially expressed enzymes and proteins
      from transgenic and nontransgenic soybean seeds. Analysis of malondialdehyde,
      ascorbate peroxidase (EC 1.11.1.11), glutathione reductase (EC 1.6.4.2), and
      catalase (EC 1.11.1.6) revealed higher levels (29.8, 30.6, 71.4, and 35.3%,
      respectively) in transgenic seeds than in nontransgenic seeds. Separation of
      soybean seed proteins was done by two-dimensional polyacrylamide gel
      electrophoresis, and 192 proteins were identified by matrix-assisted laser
      desorption/ionization (MALDI) quadrupole time-of-flight (QTOF) mass spectrometry
      (MS) and electrospray ionization (ESI) QTOF MS. Additionally, the enzyme CP4
      EPSPS, involved in the genetic modification, was identified by enzymatic
      digestions using either trypsin or chymotrypsin and ESI-QTOF MS/MS for
      identification. From the proteins identified, actin fragment, cytosolic glutamine
      synthetase, glycinin subunit G1, and glycine-rich RNA-binding protein were shown
      to be differentially expressed after analysis using the two-dimensional
      difference gel electrophoresis technique, and applying a regulator factor of 1.5
      or greater.

PMID- 21947013
TI  - Analysis of multi-class preservatives in leave-on and rinse-off cosmetics by
      matrix solid-phase dispersion.
AB  - Matrix solid-phase extraction has been successfully applied for the determination
      of multi-class preservatives in a wide variety of cosmetic samples including
      rinse-off and leave-on products. After extraction, derivatization with acetic
      anhydride, and gas chromatography-mass spectrometry analysis were performed.
      Optimization studies were done on real non-spiked and spiked leave-on and rinse
      off cosmetic samples. The selection of the most suitable extraction conditions
      was made using statistical tools such as ANOVA, as well as factorial experimental
      designs. The final optimized conditions were common for both groups of cosmetics
      and included the dispersion of the sample with Florisil (1:4), and the elution of
      the MSPD column with 5 mL of hexane/acetone (1:1). After derivatization, the
      extract was analyzed without any further clean-up or concentration step.
      Accuracy, precision, linearity and detection limits were evaluated to assess the
      performance of the proposed method. The recovery studies on leave-on and rinse
      off cosmetics gave satisfactory values (>78% for all analytes in all the samples)
      with an average relative standard deviation value of 4.2%. The quantification
      limits were well below those set by the international cosmetic regulations,
      making this multi-component analytical method suitable for routine control. The
      analysis of a broad range of cosmetics including body milk, moisturizing creams,
      anti-stretch marks creams, hand creams, deodorant, shampoos, liquid soaps,
      makeup, sun milk, hand soaps, among others, demonstrated the high use of most of
      the target preservatives, especially butylated hydroxytoluene, methylparaben,
      propylparaben, and butylparaben.

PMID- 21947012
TI  - An efficient design strategy for a whole-cell biosensor based on engineered
      ribosome binding sequences.
AB  - In prokaryotes, the ribosome binding sequence (RBS), located in the 5'
      untranslated region (5' UTR) of an mRNA, plays a critical role in enhancing mRNA
      translation and stability. To evaluate the effect of the RBS on the sensitivity
      and signal intensity of an environmental whole-cell biosensor, three Escherichia
      coli-based biosensors that respond to benzene, toluene, ethylbenzene, and the
      xylenes (BTEX) were constructed; the three biosensors have the same Pu promoter
      and xylR regulator from the Pseudomonas putida TOL plasmid but differ in the
      engineered RBS in their reporter genes. The results from time and dose-dependent
      induction of luminescence activity by 2-chlorotoluene showed that the BTEX-SE and
      BTEX-SD biosensors with engineered RBS had signal intensities approximately 10-35
      times higher than the primary BTEX-W biosensor. The limits of detection (LOD) of
      the BTEX-SE and BTEX-SD biosensors were also significantly lower than the LOD of
      the BTEX-W biosensor (20 +/- 5 MUmol L(-1) and 25 +/- 5 MUmol L(-1) vs. 120 +/-
      10 MUmol L(-1)). Moreover, the BTEX-SE and BTEX-SD biosensors responded three
      times more rapidly to the analytes. These results suggest that rationally
      designed RBS in the 5' UTR of a reporter gene may be a promising strategy for
      increasing the sensitivity, signal intensity, and response speed of whole-cell
      biosensors.

PMID- 21947014
TI  - Outlining of the detailed structures in sectioned images from Visible Korean.
AB  - PURPOSE: Sectioned images of cadavers enable creation of realistic three
      dimensional (3D) models. In order to build a 3D model of a structure, the
      structure has to be outlined in the sectioned images. The outlining process is
      time consuming; therefore, users want to be provided with outlined images. The
      more detailed structures are outlined, the greater potential for wider
      application of the outlined images. METHODS: In the Visible Korean, sectioned
      images (intervals 0.2 mm) of the entire body of a male cadaver were prepared. In
      the available 1,702 sectioned images (intervals 1 mm), 937 structures were
      outlined over a period of 8 years. The outlined images were altered to black
      filled images for each structure; black-filled images were selected for
      distribution in order to maintain small file sizes. RESULTS: We attempted to
      determine whether black-filled images could be used in various situations. The
      outlines of these images were interpolated for production of new images at 0.2 mm
      intervals. The outlines were then filled with different colors for construction
      of color-filled images of all structures. Volume and surface reconstructions of
      the black-filled images were executed in order to build volume and surface
      models. CONCLUSION: The black-filled images with corresponding sectioned images
      presented here are the source of realistic 3D models for use in medical
      simulation systems.

PMID- 21947015
TI  - Investigation of the mechanical properties of the plantar aponeurosis.
AB  - INTRODUCTION: The aim of this work was to obtain a preliminary investigation of
      the mechanical properties of the human plantar aponeurosis based on regional
      observation, in order to rationally plan a subsequent larger experimental
      campaign and develop suited constitutive models to characterize the mechanical
      response of this tissue. MATERIALS AND METHODS: Different in vitro mechanical
      tests were developed on eleven samples taken from the plantar aponeurosis of
      human cadaver (man, age 78 years). The samples were tested along the distal
      proximal direction. Range of elasticity of the tissue, development of damage
      phenomena and stress relaxation at different levels of strain were evaluated.
      RESULTS: The strength of the tissue was found in the order of that proposed in
      previous works, with peak stress of about 12.5 MPa. The compliance of the plantar
      aponeurosis was in line with in vivo evaluation. A softening behaviour appeared
      for tensile strain larger than 12%. In relaxation tests, the stress was reduced
      of 35-40% in 120 s. The percentage stress relaxation was found independent on the
      level of the applied strain. DISCUSSION: The evaluation of the mechanical
      characteristics is fundamental for a subsequent development of numerical models
      of the plantar aponeurosis. Such approach is helpful to understand its response
      to overuse, but also to understand the clinical results of different manual and
      physical therapies that use warm, pressure or stretch to modify this tissue.

PMID- 21947016
TI  - Reflections on my career as a urogynecologist.

PMID- 21947017
TI  - Urogynaecology: my view.

PMID- 21947018
TI  - Perfluoroalkylation in flow microreactors: generation of perfluoroalkyllithiums
      in the presence and absence of electrophiles.
AB  - Perfluoroalkyllithiums were effectively generated from perfluoroalkyl halides in
      the presence and absence of electrophiles using flow microreactor systems. The in
      situ trapping with electrophile is conducted at much higher temperatures than
      those required for batch macro reactors. The subsequent trapping method is quite
      effective for highly reactive electrophiles that are not compatible with the
      lithiation process.

PMID- 21947020
TI  - On the unprecedented level of dinitrogen activation in the calix[4]arene complex
      of Nb(III).
AB  - The calix[4]arene niobium(III) complex ([L]Nb-N=N-Nb[L] where [L] = p-tert
      butylcalix[4]arene), reported to bind N(2) in a MU(2)-linear dimeric capacity and
      to activate the N(2) triple bond to 1.39 A, corresponding to the longest N(2)
      bond known in the end-on coordination mode, was subjected to a computational
      investigation involving both density functional and wavefunction based methods to
      establish the basis for the unprecedented level of activation. Replacement of the
      calix[4]arene ligand with hydroxide or methoxide ligands reveals that the organic
      backbone structure of the calix[4]arene ligand exerts negligible electronic
      influence over the metal centre, serving only to geometrically constrain the
      coordinating phenoxide groups. A fragment bonding analysis shows that metal-to
      dinitrogen pi* backbonding is the principal Nb-N interaction, providing a strong
      electronic basis for analogy with other well-characterised three- and four
      coordinate complexes which bind N(2) end-on. While the calculated structure of
      the metallacalix[4]arene unit is reproduced with high accuracy, as is also the Nb
      Nb separation, the calculated equilibrium geometry of the complex under a variety
      of conditions consistently indicates against a 1.39 A activation of the N(2)
      bond. Instead, the calculated N-N distances fall within the range 1.26-1.30 A, a
      result concordant with closely related three- and four-coordinate MU(2)-N(2)
      complexes as well as predictions derived from trends in N-N stretching frequency
      for a number of crystallographically characterized linear N(2) activators. A
      number of potential causes for this bond length discrepancy are explored.

PMID- 21947019
TI  - Stridor at birth predicts poor outcome in neonates with myelomeningocele.
AB  - BACKGROUND: Stridor, associated with vocal cord paralysis, in neonates with
      myelomeningocele (MMC) is a recognized symptom related to Chiari II malformation
      (CM). In most children, stridor appears after birth. Control of hydrocephalus, if
      present, and urgent decompression of the CM are recommended for treatment of
      these patients. Such management typically improves symptoms. Occasionally,
      stridor is present at birth and may be secondary, in part, to maldevelopment or
      prenatal ischemia of the brain stem, rather than treatable compression. There is
      minimal literature describing the outcome after Chiari decompression in this
      population. The purpose of this study was to review the outcomes of neonates with
      MMC and stridor at birth and compare it to MMC patients who develop stridor
      later. We hypothesized that unlike stridor which develops after birth, stridor at
      birth predicts a dismal outcome, despite aggressive surgical treatment. METHODS:
      Retrospective review of newborns with MMC and CM was performed in our institution
      from 1975 to 2010. Patients with stridor at birth and those who developed stridor
      later in infancy were identified. Outcomes were analyzed. Autopsy findings were
      reviewed when available. RESULTS: Six patients with MMC who presented with
      stridor at birth were identified. Five of these patients had decompression of CM
      and treatment of hydrocephalus, if present, within the first 2 weeks of life. All
      patients died: three within 1 month and the oldest at 62 months. In the three
      patients with autopsies, vernix caseosa meningitis was present. Eight patients
      presented with stridor later in infancy. CM decompression was performed in seven
      of them. One patient out of the seven with late onset of stridor died at 13
      months after CM surgery. The mortality rate after CM decompression was worse in
      patients with stridor at birth than those presenting later with stridor (chi
      square p = 0.015). CONCLUSIONS: In newborns with MMC, stridor at birth may
      predict dismal outcome despite CM decompression. Unlike the situation in neonates
      who develop stridor after birth, the outcome in those presenting with stridor at
      birth does not seem to be impacted by decompression of the CM. Nonoperative
      management may be an option to offer in this population. Additionally, vernix
      caseosa meningitis may contribute to the severe irreversible brain stem
      dysfunction in these newborns.

PMID- 21947021
TI  - Intrinsically fluorescent nanoparticles with excellent stability based on a
      highly crosslinked organic-inorganic hybrid polyphosphazene material.
AB  - A series of intrinsically fluorescent particles were synthesized, including
      nanoparticles with independently tunable diameters, nanotubes and microspheres,
      based on a highly crosslinked organic-inorganic hybrid polyphosphazene material.
      The nanoparticles exhibit high fluorescent intensity and excellent thermal and
      photobleaching stability, and can be well dispersed in both aqueous and organic
      media.

PMID- 21947022
TI  - 18F-FDG PET/CT for diagnosing infectious complications in patients with severe
      neutropenia after intensive chemotherapy for haematological malignancy or stem
      cell transplantation.
AB  - PURPOSE: Between 30 and 50% of febrile neutropenic episodes are accounted for by
      infection. C-reactive protein (CRP) is a nonspecific parameter for infection and
      inflammation but might be employed as a trigger for diagnosis. The aim of the
      study was to evaluate whether (18)F-fluorodeoxyglucose (FDG) positron emission
      tomography (PET)/CT can be used to detect inflammatory foci in neutropenic
      patients with elevated CRP and whether it helps to direct treatment. METHODS:
      Twenty-eight consecutive patients with neutropenia as a result of intensive
      chemotherapy for haematological malignancies or myeloablative therapy for
      haematopoietic stem cell transplantation were prospectively included. (18)F-FDG
      PET/CT was added to the regular diagnostic workup once the CRP level rose above
      50 mg/l. RESULTS: Pathological FDG uptake was found in 26 of 28 cases despite
      peripheral neutrophil counts less than 0.1 * 10(-9)/l in 26 patients: in the
      digestive tract in 18 cases, around the tract of the central venous catheter
      (CVC) in 9 and in the lungs in 7 cases. FDG uptake in the CVC tract was
      associated with coagulase-negative staphylococcal bacteraemia (p < 0.001) and
      deep venous thrombosis (p = 0.002). The number of patients having Streptococcus
      mitis bacteraemia appeared to be higher in patients with grade 3 oesophageal FDG
      uptake (p = 0.08). Pulmonary FDG uptake was associated with the presence of
      invasive fungal disease (p = 0.04). CONCLUSION: (18)F-FDG PET/CT scanning during
      chemotherapy-induced febrile neutropenia and increased CRP is able to detect
      localized foci of infection and inflammation despite the absence of circulating
      neutrophils. Besides its potential role in detecting CVC-related infection during
      febrile neutropenia, the high negative predictive value of (18)F-FDG PET/CT is
      important for avoiding unnecessary diagnostic tests and therapy.

PMID- 21947023
TI  - Complex coronary artery anatomy in a patient with prolapsing left atrial myxoma.
AB  - The case of an asymptomatic patient with prolapsing left atrial myxoma, in whom
      preoperative coronary angiography revealed a rare coronary artery anatomy in the
      absence of atherosclerotic obstructive disease, is presented. There was a type IV
      dual left anterior descending (LAD) artery with intraseptal course of the right
      aortic sinus-connected (long) LAD artery and an ectopic left circumflex artery
      originating from the right aortic sinus and having a retroaortic course. The
      patient underwent successful surgical excision of the mass which was confirmed by
      histology to be cardiac myxoma. This particular coronary artery anatomy has only
      been described once, and this is the first reported case of its combination with
      cardiac myxoma. This report highlights the importance of differentiating between
      the possible courses of such ectopic coronary arteries. The angiographic signs
      which enabled differentiation of the intraseptal course of the long LAD artery
      from the malignant interarterial course with which it is frequently confused are
      presented.

PMID- 21947024
TI  - Stroke prevention in non-valvular atrial fibrillation: can warfarin do better?

PMID- 21947025
TI  - Endoscopy: High-definition imaging and NBI-improving colonic imaging?

PMID- 21947026
TI  - Detection of protein interactions in plant using a gateway compatible bimolecular
      fluorescence complementation (BiFC) system.
AB  - We have developed a BiFC technique to test the interaction between two proteins
      in vivo. This is accomplished by splitting a yellow fluorescent protein (YFP)
      into two non-overlapping fragments. Each fragment is cloned in-frame to a gene of
      interest. These constructs can then be co-transformed into Nicotiana benthamiana
      via Agrobacterium mediated transformation, allowing the transit expression of
      fusion proteins. The reconstitution of YFP signal only occurs when the inquest
      proteins interact (1-7). To test and validate the protein-protein interactions,
      BiFC can be used together with yeast two hybrid (Y2H) assay. This may detect
      indirect interactions which can be overlooked in the Y2H. Gateway technology is a
      universal platform that enables researchers to shuttle the gene of interest (GOI)
      into as many expression and functional analysis systems as possible(8,9). Both
      the orientation and reading frame can be maintained without using restriction
      enzymes or ligation to make expression-ready clones.  As a result, one can
      eliminate all the re-sequencing steps to ensure consistent results throughout the
      experiments. We have created a series of Gateway compatible BiFC and Y2H vectors
      which provide researchers with easy-to-use tools to perform both BiFC and Y2H
      assays(10). Here, we demonstrate the ease of using our BiFC system to test
      protein-protein interactions in N. benthamiana plants.

PMID- 21947027
TI  - Time-resolved photoelectron spectroscopy: from wavepackets to observables.
AB  - Time-resolved photoelectron spectroscopy (TRPES) is a powerful tool for the study
      of intramolecular dynamics, particularly excited state non-adiabatic dynamics in
      polyatomic molecules. Depending on the problem at hand, different levels of TRPES
      measurements can be performed: time-resolved photoelectron yield; time- and
      energy-resolved photoelectron yield; time-, energy-, and angle-resolved
      photoelectron yield. In this pedagogical overview, a conceptual framework for
      time-resolved photoionization measurements is presented, together with discussion
      of relevant theory for the different aspects of TRPES. Simple models are used to
      illustrate the theory, and key concepts are further amplified by experimental
      examples. These examples are chosen to show the application of TRPES to the
      investigation of a range of problems in the excited state dynamics of molecules:
      from the simplest vibrational wavepacket on a single potential energy surface; to
      disentangling intrinsically coupled electronic and nuclear motions; to
      identifying the electronic character of the intermediate states involved in non
      adiabatic dynamics by angle-resolved measurements in the molecular frame, the
      most complete measurement.

PMID- 21947028
TI  - Performance comparison of exome DNA sequencing technologies.
AB  - Whole exome sequencing by high-throughput sequencing of target-enriched genomic
      DNA (exome-seq) has become common in basic and translational research as a means
      of interrogating the interpretable part of the human genome at relatively low
      cost. We present a comparison of three major commercial exome sequencing
      platforms from Agilent, Illumina and Nimblegen applied to the same human blood
      sample. Our results suggest that the Nimblegen platform, which is the only one to
      use high-density overlapping baits, covers fewer genomic regions than the other
      platforms but requires the least amount of sequencing to sensitively detect small
      variants. Agilent and Illumina are able to detect a greater total number of
      variants with additional sequencing. Illumina captures untranslated regions,
      which are not targeted by the Nimblegen and Agilent platforms. We also compare
      exome sequencing and whole genome sequencing (WGS) of the same sample,
      demonstrating that exome sequencing can detect additional small variants missed
      by WGS.

PMID- 21947030
TI  - Multi-wall carbon nanotube aqueous dispersion monitoring by using A4F-UV-MALS.
AB  - In this work, the potentiality of asymmetrical flow field-flow fractionation
      (A4F) hyphenated to UV detector and multi-angle light scattering (MALS) was
      investigated for accurately determining multi-walled carbon nanotube (MWCNT)
      length and its corresponding dispersion state in aqueous medium. Fractionation
      key parameters were studied to obtain a method robust enough for heterogeneous
      sample characterization. The main A4F conditions were 10(-5) mL min(-1)
      NH(4)NO(3), elution flow of 1 mL min(-1), and cross flow of 2 mL min(-1). The
      recovery was found to be (94 +/- 2)%. Online MALS analysis of eluted MWCNT
      suspension was performed to obtain length distribution. The length measurements
      were performed with a 4% relative standard deviation, and the length values were
      shown to be in accordance with expected ones. The capabilities of A4F-UV-MALS to
      size characterize various MWCNT samples and differentiate them according to their
      manufacturing process were evaluated by monitoring ball-milled MWCNT and MWCNT
      dispersions. The corresponding length distributions were found to be over 150-650
      and 150-1,156 nm, respectively. A4F-UV-MALS was also used to evaluate MWCNT
      dispersion state in aqueous medium according to the surfactant concentration and
      sonication energy involved in the preparation of the dispersions. More
      especially, the presence or absence of aggregates, number and size of different
      populations, as well as size distributions were determined. A sodium dodecyl
      sulfate concentration of 15 to 30 mmol L(-1) and a sonication energy ranged over
      20-30 kJ allow obtaining an optimal MWCNT dispersion. It is especially valuable
      for studying nanomaterials and checking their manufacturing processes, size
      characterization being always of high importance.

PMID- 21947029
TI  - CD140a identifies a population of highly myelinogenic, migration-competent and
      efficiently engrafting human oligodendrocyte progenitor cells.
AB  - Experimental animals with myelin disorders can be treated by transplanting
      oligodendrocyte progenitor cells (OPCs) into the affected brain or spinal cord.
      OPCs have been isolated by their expression of gangliosides recognized by mAb
      A2B5, but this marker also identifies lineage-restricted astrocytes and immature
      neurons. To establish a more efficient means of isolating myelinogenic OPCs, we
      sorted fetal human forebrain cells for CD140a, an epitope of platelet derived
      growth factor receptor (PDGFR)alpha, which is differentially expressed by OPCs.
      CD140a(+) cells were isolated as mitotic bipotential progenitors that initially
      expressed neither mature neuronal nor astrocytic phenotypic markers, yet could be
      instructed to either oligodendrocyte or astrocyte fate in vitro. Transplanted
      CD140a(+) cells were highly migratory and robustly myelinated the hypomyelinated
      shiverer mouse brain more rapidly and efficiently than did A2B5(+)cells.
      Microarray analysis of CD140a(+) cells revealed overexpression of the
      oligodendroglial marker CD9, suggesting that CD9(+)/CD140a(+) cells may
      constitute an even more highly enriched population of myelinogenic progenitor
      cells.

PMID- 21947031
TI  - Z-formamidoximes in molecular folding and macrocycles.
AB  - The formamidoxime configurational Z isomer coupled with the pyridylbiscarboxamide
      conformational codon were used to fold planar, curved structures. When embedded
      into macrocycles, this folded motif promotes dimerization through pi-pi stacking
      and hydrogen-bonding and the formation of tubules akin to molecular channels in
      the solid state.

PMID- 21947032
TI  - High hyperdiploid acute lymphoblastic leukemia in adults shows clonal
      heterogeneity and chromosomal instability at diagnosis and during the course of
      the disease.

PMID- 21947033
TI  - Phalangeal quantitative ultrasound in 1,719 children and adolescents with bone
      disorders.
AB  - SUMMARY: We measured bone properties by phalangeal quantitative ultrasound in
      1,719 pediatric patients with bone disorders, classifying them according to
      fracture status. Quantitative ultrasound discriminated fractured and nonfractured
      pediatric patients and enabled us to stratify fractured patients into classes
      according to the severity of the causative trauma (spontaneous, minimal trauma,
      appropriate trauma fractures). INTRODUCTION: The correlation between quantitative
      bone measurements and fractures is poorly established in pediatric patients with
      bone disorders. We correlated phalangeal quantitative ultrasound (QUS) and
      fracture history in children and adolescents with bone disorders and evaluated
      the ability of QUS to recognize fractured patients. METHODS: Amplitude-dependent
      speed of sound (AD-SoS) and bone transmission time (BTT) were measured in 1,719
      pediatric patients with bone disorders and related to fracture history. The
      patients were classified as (1) spontaneously (77), (2) minimal trauma (101), or
      (3) appropriate trauma fractured (206), and (4) nonfractured (1,335). The
      likelihood of fracture according to QUS was calculated as odds ratio per SD
      decrease (OR/SD), and the effectiveness in discriminating fractured patients was
      evaluated by receiver operating characteristic (ROC) analysis. The influence of
      age, sex, puberty, height, and BMI was explored by respective adjustments and
      multiple logistic regression. RESULTS: Fractured patients showed significantly
      reduced AD-SoS and BTT standard deviation score (-0.32 +/- 1.54 and -0.78 +/-
      1.49) compared to nonfractured subjects (0.43 +/- 1.63 and -0.11 +/- 1.34). QUS
      measurements paralleled the causative trauma severity, ranging from the lowest
      values in spontaneously fractured patients to normal values in appropriate trauma
      fractured subjects. The OR/SD were increasingly higher in appropriate trauma
      fractured, minimal trauma fractured, and spontaneously fractured patients. At ROC
      analysis, both parameters proved to have significant discrimination power in
      recognizing spontaneously and minimal trauma-fractured patients. CONCLUSIONS: QUS
      identifies fractured pediatric patients with bone disorders, reflecting the
      severity of the causative trauma with a high discrimination power for fragility
      fractures.

PMID- 21947034
TI  - Spinal meningioma in childhood: clinical features and treatment.
AB  - OBJECT: The purpose of this retrospective study is to determine the clinical
      characteristics and the prognosis of the spinal meningioma in childhood (under 18
      years of age) based on the treatment at our institution. METHODS: Ten spinal
      meningioma cases in children were treated during the last 9 years. The clinical
      data was retrospectively analyzed and the results were compared with those in the
      literature. RESULTS: The series included eight males and two females and the mean
      age was 13.2 years. The most common initial symptoms were pain (6/10) and the
      common signs were limb weakness (4/10) and gait disturbance (2/10) and distal
      paresthesia (1/10) and bladder disturbance (1/10). Four patients had other
      clinical signs of neurofibromatosis type II (NF-2) such as tumors elsewhere. All
      the tumors were located in cervical and thoracic vertebrae. Resection according
      to Simpson Grade I (6/10), II (2/10), III (1/10), and IV (1/10) were performed.
      Grade II meningiomas accounted for 3/10 in this series. All patients were
      followed up with mean follow-up period of 43 months. Seven patients had
      recurrence of the tumor in that period and one had died. CONCLUSIONS: Spinal
      meningioma is an uncommon pediatric neoplasm and has a poor prognosis. It has a
      male predominance and is inclined to be associated with NF-2, and those that are
      associated with higher pathologic subtypes and NF-2 have more unfavorable
      outcome. Every effort should be made to achieve total removal which may decrease
      the incidence of recurrence.

PMID- 21947035
TI  - Desmoplastic infantile astrocytoma: recurrence with malignant transformation into
      glioblastoma: a case report.
AB  - Desmoplastic infantile astrocytoma (DIA) is an uncommon brain tumor of early
      infancy. The tumor is characterized by a lobar location, glial histology, and
      excellent prognosis after surgical removal. DIA and a similar tumor, desmoplastic
      infantile ganglioglioma (DIG) have been considered to be benign neoplasms, but
      the prognosis of DIA and DIG is currently under question as atypical and
      aggressive clinical features of the tumors have been reported. We encountered a
      patient who was diagnosed with DIA at the age of 22 months and exhibited tumor
      recurrence 8 years later. Surgical removal of the recurred tumor revealed that
      the tumor had transformed to overt glioblastoma. This case demonstrates that DIA
      is not an absolutely benign tumor and that careful clinical surveillance is
      needed during the follow-up period.

PMID- 21947036
TI  - The presence of three repeats in the 5' UTR region of thymidylate synthase (TS)
      is associated with increased TS mRNA expression in cultured human cancer cell
      lines in vitro.
AB  - Thymidylate synthase (TS) gene contains 28-bp polymorphic sequence and 6-bp
      insert at the 5'- and 3'-untranslated region, respectively. We investigated the
      role of these two polymorphic traits on TS mRNA expression in nine different
      cultured human cancer cell lines in vitro. Three cell lines each were 2R/2R,
      2R/3R and 3R/3R genotypes. Six of the nine cell lines tested homozygous for the
      presence of 6-bp insert (+6/+6) and the rest three lacked this insert (-6/-6). TS
      expression analyses associated homozygous three repeats (3R/3R) to higher TS
      expression.

PMID- 21947037
TI  - Comprehensive two-dimensional gas chromatography, a valuable technique for
      screening and semiquantitation of different chemical compounds in ultrafine 30 nm
      and 50 nm aerosol particles.
AB  - Comprehensive two dimensional gas chromatography-time-of-flight mass spectrometry
      (GC*GC-TOF-MS) was used for screening and semiquantitation of semivolatile
      organic compounds in aerosol particles. As the volatility was a prerequisite
      parameter for the analysis, some compounds were transformed via derivatization
      such as silylation into more volatile ones. The identification of the analytes
      was made by comparing the GC retention indices and the TOF mass spectra with the
      NIST and the Golm metabolome database reference libraries. The data treatment was
      simplified by exploiting an additional classification of the identified
      compounds, namely the main functional group or specific element present in the
      molecule leading to different groups of compounds. This methodology was applied
      to identify compounds in 30 +/- 4 nm, 50 +/- 5 nm and total suspended particles
      (TSP) collected during spring and autumn of 2009 and summer of 2010 at the
      Station for Measuring Forest Ecosystem Atmosphere Relations (SMEAR II) at
      Hyytiala (Finland). The number of identified compounds was higher than 400, which
      were the most relevant compounds present in the samples, in terms of
      concentrations. The analysis of aerosol particles of different sizes, collected
      simultaneously, revealed that the number of compounds increased with the particle
      size whereas the normalized response factor decreased in most of the cases,
      aldehydes being an exception. This decrease could be associated with the
      formation or aggregation of new compounds onto the particles when they grow in
      the atmosphere.

PMID- 21947038
TI  - Uniform irradiation of adjustable target spots in high-power laser driver.
AB  - For smoothing and shaping the on-target laser patterns flexibly in high-power
      laser drivers, a scheme has been developed that includes a zoom lens array and
      two-dimensional smoothing by spectral dispersion (SSD). The size of the target
      pattern can be controlled handily by adjusting the focal length of the zoom lens
      array, while the profile of the pattern can be shaped by fine tuning the distance
      between the target and the focal plane of the principal focusing lens. High
      frequency stripes inside the pattern caused by beamlet interference are wiped off
      by spectral dispersion. Detailed simulations indicate that SSD works somewhat
      differently for spots of different sizes. For small spots, SSD mainly smooths the
      intensity modulation of low-to-middle spatial frequency, while for large spots,
      SSD sweeps the fine speckle structure to reduce nonuniformity of middle-to-high
      frequency. Spatial spectra of the target patterns are given and their uniformity
      is evaluated.

PMID- 21947039
TI  - Ion beam machining error control and correction for small scale optics.
AB  - Ion beam figuring (IBF) technology for small scale optical components is
      discussed. Since the small removal function can be obtained in IBF, it makes
      computer-controlled optical surfacing technology possible to machine precision
      centimeter- or millimeter-scale optical components deterministically. Using a
      small ion beam to machine small optical components, there are some key problems,
      such as small ion beam positioning on the optical surface, material removal rate,
      ion beam scanning pitch control on the optical surface, and so on, that must be
      seriously considered. The main reasons for the problems are that it is more
      sensitive to the above problems than a big ion beam because of its small beam
      diameter and lower material ratio. In this paper, we discuss these problems and
      their influences in machining small optical components in detail. Based on the
      identification-compensation principle, an iterative machining compensation method
      is deduced for correcting the positioning error of an ion beam with the material
      removal rate estimated by a selected optimal scanning pitch. Experiments on phi10
      mm Zerodur planar and spherical samples are made, and the final surface errors
      are both smaller than lambda/100 measured by a Zygo GPI interferometer.

PMID- 21947040
TI  - Effect of different epitaxial structures on GaAs photoemission.
AB  - The quantum efficiency equations of two different structure reflection-mode GaAs
      photocathodes with back interface recombination velocity have been solved from
      the diffusion equations. One structure consists of GaAs substrate and an
      epitaxial GaAs active layer (GaAs-GaAs) and another structure consists of GaAs
      substrate, an epitaxial AlGaAs buffer layer, and a GaAs active layer (AlGaAs
      GaAs). The experimental results show that the quantum efficiency of long
      wavelength photons and the integral sensitivities for GaAs-GaAs cathodes both
      increase with the increase in the active layer thickness, which is due to the
      increase of electron diffusion length. The quantum efficiency of long-wavelength
      photons and the integral sensitivity of AlGaAs-GaAs cathodes are greater than
      those of GaAs-GaAs cathodes with an identical active layer thickness, which is
      attributed to the AlGaAs buffer layer. The buffer layer can reflect electrons and
      improve the quality of the GaAs active layer. Through the theoretical simulation,
      we found the active layer thickness for AlGaAs-GaAs cathodes has an optimum value
      at which the cathodes achieve the maximum sensitivity.

PMID- 21947041
TI  - Image rotation and translation measurement based on double phase-encoded joint
      transform correlator.
AB  - An image rotation and translation measurement technology based on a double phase
      encoded joint transform correlator (DPEJTC) is proposed. The reference and the
      target images are Fourier transformed. Then the magnitude of the Fourier
      transformed reference (MFR) and target (MFT) images are multiplied with a high
      pass emphasis filter and transformed from Cartesian space into polar space.
      Rotation between the reference and the target image is obtained by measuring the
      emphasized MFR and MFT in polar coordinates by the DPEJTC. The target image is
      rotated by the rotation angle in the inverse orientation to get the rotation
      correction target image. Finally, translation between the reference and the
      target image is obtained through measuring the reference and the rotation
      correction target image by the DPEJTC. Results based on digital computation are
      given to verify our proposal. A possible optical setup is suggested.

PMID- 21947042
TI  - Performance analysis of a fiber Bragg grating filter-based strain/temperature
      sensing system based on a modified Gaussian function approximation method.
AB  - This paper analyzes the performance of a fiber Bragg grating (FBG) filter-based
      strain and/or temperature sensing system based on a modified Gaussian function
      (MGF) approximation method. Instead of using a conventional Gaussian function, we
      propose the MGF, which can capture the characteristics of the sidelobes of the
      reflected spectrum, to model the FBG sensor and filter. We experimentally
      demonstrate that, by considering the contributions of the sidelobes with the MGF
      approximation method, behaviors of the FBG filter-based FBG displacement and/or
      temperature sensing system can be predicted more accurately. The predicted
      behaviors include the saturation, the sensitivity, the sensing range, and the
      optimal initial Bragg wavelengths of the FBG sensing system.

PMID- 21947043
TI  - Manipulating wavelength-selective emission with heterogeneous photonic crystals.
AB  - The usual near-field radiation profile of a light beam emanating from a photonic
      crystal waveguide (PCW) has a main lobe at the center line of the waveguide.
      However, a centrally symmetric profile for the emission pattern with two
      sidelobes can be required in some applications, e.g., Y-type power dividers,
      wavelength multiplexers, and semiconductor lasers. With such motivations in mind,
      we present the design of a compact structure that deflects the beam propagation
      direction in this manner. The idea utilizes the manipulation of the dispersion
      diagram of cascaded photonic crystals by exploiting the bandgap and self
      collimation properties. The waveguide mode in the PCW can be transformed from a
      propagating mode into a diffusive one by altering the filling factor, which, in
      turn, leads to off-axis light emission. By using the finite-difference time
      domain method, we show that the emission takes place into free space at the
      inclined output surfaces of the PCW with deviation angles of +/-45 degrees .

PMID- 21947044
TI  - Improvement of digital photoelasticity based on camera response function.
AB  - Studies on photoelasticity have been conducted by many researchers in recent
      years, and many equations for photoelastic analysis based on digital images were
      proposed. While these equations were all presented by the light intensity emitted
      from the analyzer, pixel values of the digital image were actually used in the
      real calculations. In this paper, a proposal of using relative light intensity
      obtained by the camera response function to replace the pixel value for
      photoelastic analysis was investigated. Generation of isochromatic images based
      on relative light intensity and pixel value were compared to evaluate the
      effectiveness of the new approach. The results showed that when relative light
      intensity was used, the quality of an isochromatic image can be greatly improved
      both visually and quantitatively. We believe that the technique proposed in this
      paper can also be used to improve the performance for the other types of
      photoelastic analysis using digital images.

PMID- 21947045
TI  - Analysis of the colorimetric properties of goniochromatic colors using the
      MacAdam limits under different light sources.
AB  - Technological innovation in all areas has led to the appearance in recent years
      of new metallic and pearlescent materials, yet no exhaustive studies have been
      conducted to assess their colorimetric capabilities. The chromatic variability of
      these special-effect pigments may largely be due to the three-dimensional effect
      of their curved shapes and orientations when they are directionally or diffusely
      illuminated. Our study examines goniochromatic colors using the optimal colors
      (MacAdam limits) associated with normal colors (photometric scale of relative
      spectral reflectance from 0 to 1) under certain conventional illuminants and
      other light sources. From a database of 91 metallic and interference samples and
      using a multi-gonio-spectrophotometer, we analyzed samples with lightness values
      of more than 100 and others with lightness values of less than 100, but with
      higher chromaticities than optimal colors, which places them beyond the MacAdam
      limits. Our study thus demonstrates the existence of chromatic perceptions beyond
      the normal solid color associated with these materials and independent of the
      light source. The challenge for future research, therefore, is to replicate and
      render these color appearances in current and future color reproduction
      technologies for computer graphics.

PMID- 21947046
TI  - Selective edge enhancement using anisotropic vortex filter.
AB  - In optical image processing, selective edge enhancement is important when it is
      preferable to emphasize some edges of an object more than others. We propose a
      new method for selective edge enhancement of amplitude objects using the
      anisotropic vortex phase mask by introducing anisotropy in a conventional vortex
      mask with the help of the sine function. The anisotropy is capable of edge
      enhancement in the selective region and in the required direction by changing the
      power and offset angle, respectively, of the sine function.

PMID- 21947047
TI  - Optical bistability in metal-insulator-metal plasmonic waveguide with nanodisk
      resonator containing Kerr nonlinear medium.
AB  - We numerically investigate the optical bistability effect in the metal-insulator
      metal waveguide with a nanodisk resonator containing a Kerr nonlinear medium. It
      is found that the increase of the refractive index, which is induced by enhancing
      the incident intensity, can cause a redshift for the resonance wavelength. The
      local resonant field excited in the nanodisk cavity can significantly increase
      the Kerr nonlinear effect. In addition, an obvious bistability loop is observed
      in the proposed structure. This nonlinear structure can find important
      applications for all-optical switching in highly integrated optical circuits.

PMID- 21947048
TI  - Angular diagram of broadband emission of millimeter-sized water droplets exposed
      to gigawatt femtosecond laser pulses.
AB  - We report on the experiments on the interaction of gigawatt femtosecond laser
      pulses with suspended millimeter-sized water droplets. The transparent droplets
      experienced laser-induced breakdown and explosive boiling up and emitted a
      broadband radiation. This radiation covers the spectral range from 450 to 1100 nm
      and consists of the spectrum of laser pulse scattered and transformed by the
      droplet due to self-phase modulation and plasma emission produced in water during
      photoionization. The droplet emission spectrum showed remarkable broadening at
      all viewing angles and is maximal in the direction of the laser exit from the
      droplet. The enlargement of the droplet results in additional spectral spreading
      of the emitted radiation. The depth and amount of laser pulse spectral self
      transformations upon propagation through the water droplet are simulated by means
      of numerical calculations.

PMID- 21947049
TI  - Evaluation of Kerr constant of blue-phase liquid crystals by measuring off-axis
      retardation in vertical electric field cells.
AB  - Because of the nonuniform electric field of the in-plane-switching cell in the
      thickness direction, an accurate and efficient way for evaluating the Kerr
      constant of blue-phase liquid crystal (BPLC) needs to be developed. This study
      demonstrates a method for evaluating the Kerr constant by measuring the off-axis
      induced retardation (R(th)) change in normal vertical field cells using a
      commercial polarimeter. The angle-dependent behavior of the R(th) change is
      observed as an electric-tunable positive C retarder. In this paper, a sigmoid
      fitting model has been chosen for calculating the Kerr constant for considering
      the very small intrinsic birefringence of the BPLC.

PMID- 21947050
TI  - Long-exposure filtering of turbulence-degraded wavefronts.
AB  - The quasi-static aberrations of optical telescopes are often determined using
      light from a star as the reference wavefront. We calculate the exposure time
      necessary to determine the amplitude of the phase aberrations for a given
      telescope to a given accuracy in the presence of atmospheric seeing. We implement
      a computational simulation of the atmosphere and present the root mean square of
      the generated wavefront Zernike amplitudes for a given exposure time. We find the
      exposure time tau required to reach a desired precision is strongly dependent on
      telescope diameter (tau?D(8/3)) and can be many tens of minutes in extreme cases.
      We present the results so tau can be calculated for a range of telescopes and
      atmospheric parameters.

PMID- 21947051
TI  - Zinc oxide nanoparticle based optical fiber humidity sensor having linear
      response throughout a large dynamic range.
AB  - The main objective of the present work is to develop an optical fiber relative
      humidity (RH) sensor having a linear response throughout over the widest possible
      dynamic range. We report an optical fiber RH sensor based on the evanescent wave
      absorption spectroscopy that fulfills this objective. The fiber sensor employs a
      specific nanoparticle (zinc oxide) doped sol-gel nanostructured sensing film of
      optimum thickness, synthesized over a short length of a centrally decladded
      straight and uniform optical fiber. A detailed experimental investigation is
      carried out to analyze the sensor response/characteristics. Fiber sensor response
      is observed to be linear throughout the dynamic range as wide as 4% to 96% RH.
      The observed linear sensitivity for the fiber sensor is 0.0012 RH(-1). The
      average response time of the reported sensor is observed to be as short as 0.06 s
      during the humidification. In addition, the sensor exhibited a very good degree
      of reversibility and extremely high reliability as well as repeatability.

PMID- 21947052
TI  - Optical stress sensor based on electro-optic compensation for photoelastic
      birefringence in a single crystal.
AB  - An optical stress sensor is proposed by using a single crystal with both electro
      optic and photoelastic effects. Different from previous crystal-based stress
      sensors, the proposed sensor is based on electro-optic compensation for stress
      induced birefringence and does not need an additional quarter-wave plate or
      modulator, because the stress-sensing element is simultaneously used as an
      electro-optic compensator. Candidate sensing materials include electro-optic
      crystals of the 3 m symmetry group and all glass with large Kerr coefficients. A
      primary experiment has demonstrated that the stress-induced birefringence in
      lithium niobate crystal can be compensated by its electro-optic birefringence.
      The proposed stress sensor is compact and low cost, and it is possible to achieve
      closed-loop stress measurement.

PMID- 21947053
TI  - Fabrication of a high-precision spherical micromirror by bending a silicon plate
      with a metal pad.
AB  - We demonstrate here the fabrication of a smooth mirror surface by bending a thin
      silicon plate. A spherical surface is achieved by the bending moment generated in
      the circumference of the micromirror. Both convex and concave spherical
      micromirrors are realized through the anodic bonding of silicon and Pyrex glass.
      Since the mirror surface is originated from the polished silicon surface and no
      additional etching is introduced for manufacturing, the surface roughness is thus
      limited to the polishing error. This novel approach opens possibilities for
      fabricating a smooth surface for micromirror and microlens applications.

PMID- 21947054
TI  - Diffusion dynamics of small molecules from mesoporous silicon films by real-time
      optical interferometry.
AB  - Time-dependent laser reflectometry measurements are presented as a means to
      rigorously characterize analyte diffusion dynamics of small molecules from
      mesoporous silicon (PSi) films for drug delivery and membrane physics
      applications. Calculations based on inclusion of a spatially and temporally
      dependent solute concentration profile in a one-dimensional Fickian diffusion
      flow model are performed to determine the diffusion coefficients for the selected
      prototypical polar species, sucrose (340 Da), exiting from PSi films. The
      diffusion properties of the molecules depend on both PSi pore size and film
      thickness. For films with average pore diameters between 10-30 nm and film
      thicknesses between 300-900 nm, the sucrose diffusion coefficient can be tuned
      between approximately 100 and 550 MUm2/s. Extensions of the real-time measurement
      and modeling approach for determining the diffusivity of small molecules that
      strongly interact with and corrode the internal surfaces of PSi films are also
      discussed.

PMID- 21947055
TI  - High-power picosecond terahertz-wave generation in photonic crystal fiber via
      four-wave mixing.
AB  - We demonstrate picosecond terahertz (THz)-wave generation via four-wave mixing in
      an octagonal photonic crystal fiber (O-PCF). Perfect phase-matching is obtained
      at the pump wavelength of 1.55 MUm and a generation scheme is proposed. Using
      this method, THz waves can be generated in the frequency range of 7.07-7.74 THz.
      Moreover, peak power of 2.55 W, average power of 1.53 mW, and peak conversion
      efficiency of more than -66.65 dB at 7.42 THz in a 6.25 cm long fiber are
      realized with a pump peak power of 2 kW.

PMID- 21947056
TI  - Modulation transfer function for infrared reflectarrays.
AB  - The quality of the image produced by optical reflectarrays as a function of the
      F/#, polarization, and wavelength is analyzed in this paper. The results are
      expressed as monochromatic and polychromatic modulation transfer functions. They
      show that large aperture multilevel reflectarrays perform quite close to the
      diffraction-limited case. The chromatic aberrations make these elements highly
      wavelength-selective.

PMID- 21947057
TI  - Field-of-view analysis of a polarization interference Fourier transform imaging
      spectrometer.
AB  - The Fourier transform imaging spectrometer (FTIS) is an important tool for the
      measurement of spectral information in a scene. Advances in electro-optic crystal
      systems have led to the advent of the FTIS based on polarization interference
      filters. The operation of these devices as spectrometers has been well
      characterized, but the imaging capabilities have yet to be thoroughly explored.
      We explore the field-of-view limitations that occur when using this particular
      type of FTIS.

PMID- 21947058
TI  - Myo-Myo: Yes, papa. Eating sugar? No, papa! Modulating the myocardial menu for
      imaging coronary inflammation...

PMID- 21947059
TI  - Pentacoordinate iron complexes as functional models of the distal iron in [FeFe]
      hydrogenases.
AB  - Mononuclear pentacoordinate iron complexes with a free coordination site were
      prepared as mimics of the distal Fe (Fe(d)) in the active site of [FeFe]
      hydrogenases. The complexes catalyze the electrochemical reduction of protons at
      mild overpotential.

PMID- 21947060
TI  - Amputation of a lower extremity after severe trauma.
AB  - OBJECTIVE: Serious lower extremity injuries sometimes warrant emergency
      amputation. The goal of amputation in polytrauma patients is to increase chances
      of survival, while the goal of amputation in a single limb injury is to prevent
      further complications, e.g., infection, septic shock. INDICATIONS: Rescue from
      life-threatening lower extremity bleeding in a critically injured patient. Severe
      injury of a lower extremity: crushed, burned, frozen, advanced infection.
      CONTRAINDICATIONS: Patient refusal. SURGICAL TECHNIQUE: Supine position,
      determination of resection border, skin incision, identification of nerves and
      blood vessels, osteotomy, vessel ligation, separation of blood vessels and
      nerves, final removal of tissue with amputation knife, disposal of amputated
      extremity, skin closure. POSTOPERATIVE MANAGEMENT: Wound care, careful
      compression wraps beginning on postoperative day 7, early prosthesis fitting,
      mental health care consultation. RESULTS: From January 2008 until October 2010,
      115 lower extremities were amputated at the BG Trauma Clinic in Ludwigshafen,
      Germany. A total of 42 amputations were posttraumatic and were performed in the
      clinic for trauma surgery and orthopedics. There were a total of 18 foot and toe
      amputations, 16 lower leg amputations, 5 knee amputations, and 3 above knee
      amputations. Comparison of the groups is difficult due to the varying mechanisms
      of injury and locations of amputation. Therapeutic decisions regarding emergency
      amputation are made with careful consideration of the patient.

PMID- 21947061
TI  - A prospective cohort study of light transmission platelet aggregometry for
      bleeding disorders: is testing native platelet-rich plasma non-inferior to
      testing platelet count adjusted samples?
AB  - Light transmission platelet aggregometry (LTA) is important to diagnose bleeding
      disorders. Experts recommend testing LTA with native (N) rather than platelet
      count adjusted (A) platelet-rich plasma (PRP), although it is unclear if this
      provides non-inferior, or superior, detection of bleeding disorders. Our goal was
      to determine if LTA with NPRP is non-inferior to LTA with APRP for bleeding
      disorder assessments. A prospective cohort of patients, referred for bleeding
      disorder testing, and healthy controls, were evaluated by LTA using common
      agonists, NPRP and APRP (adjusted to 250 x 109 platelets/l). Recruitment
      continued until 40 controls and 40 patients with definite bleeding disorders were
      tested. Maximal aggregation (MA) data were assessed for the detection of
      abnormalities from bleeding disorders (all causes combined to limit bias), using
      sample-type specific reference intervals. Areas under receiver-operator curves
      (AUROC) were evaluated using pre-defined criteria (area differences: < 0.15 for
      non-inferiority, > 0 for superiority). Forty-four controls and 209 patients were
      evaluated. Chart reviews for 169 patients indicated 67 had bleeding disorders, 28
      from inherited platelet secretion defects. Mean MA differences between NPRP and
      APRP were small for most agonists (ranges, controls: -3.3 to 5.8; patients: -3.0
      to 13.7). With both samples, reduced MA with two or more agonists was associated
      with a bleeding disorder. AUROC differences between NPRP and APRP were small and
      indicated that NPRP were non-inferior to APRP for detecting bleeding disorders by
      LTA, whereas APRP met superiority criteria. Our study validates using either NPRP
      or APRP for LTA assessments of bleeding disorders.

PMID- 21947063
TI  - How ion properties determine the stability of a lipase enzyme in ionic liquids: a
      molecular dynamics study.
AB  - The influence of eight different ionic liquid (IL) solvents on the stability of
      the lipase Candida antarctica lipase B (CAL-B) is investigated with molecular
      dynamics (MD) simulations. Considered ILs contain cations that are based either
      on imidazolium or guanidinium as well as nitrate, tetrafluoroborate or
      hexafluorophosphate anions. Partial unfolding of CAL-B is observed during high
      temperature MD simulations and related changes of CAL-B regarding its radius of
      gyration, surface area, secondary structure, amount of solvent close to the
      backbone and interaction strength with the ILs are evaluated. CAL-B stability is
      influenced primarily by anions in the order NO(3)(-)? BF(4)(-) < PF(6)(-) of
      increasing stability, which agrees with experiments. Cations influence protein
      stability less than anions but still substantially. Long decyl side chains, polar
      methoxy groups and guanidinium-based cations destabilize CAL-B more than short
      methyl groups, other non-polar groups and imidazolium-based cations,
      respectively. Two distinct causes for CAL-B destabilization are identified: a
      destabilization of the protein surface is facilitated mostly by strong Coulomb
      interactions of CAL-B with anions that exhibit a localized charge and strong
      polarization as well as with polar cation groups. Surface instability is
      characterized by an unraveling of alpha-helices and an increase of surface area,
      radius of gyration and protein-IL total interaction strength of CAL-B, all of
      which describe a destabilization of the folded protein state. On the other hand,
      a destabilization of the protein core is facilitated when direct core-IL
      interactions are feasible. This is the case when long alkyl chains are involved
      or when particularly hydrophobic ILs induce major conformational changes that
      enable ILs direct access to the protein core. This core instability is
      characterized by a disintegration of beta-sheets, diffusion of ions into CAL-B
      and increasing protein-IL van der Waals interactions. This process describes a
      stabilization of the unfolded protein state. Both of these processes reduce the
      folding free energy and thus destabilize CAL-B. The results of this work clarify
      the impact of ions on CAL-B stabilization. An extrapolation of the observed
      trends enables proposing novel ILs in which protein stability could be enhanced
      further.

PMID- 21947064
TI  - [Epilepsy in elderly].
AB  - Seventy-two elderly patients with a possible diagnosis of epilepsy were studied.
      A study included the evaluation of anamnesis, clinical and neurological
      examination, EEG and/or video-EEG-monitoring, MRI of the brain. The follow-up
      period was 1-5 years (on average 3 years). Epilepsy was confirmed in 58 cases.
      Symptomatic partial epilepsy was diagnosed in 43,1% patients, cryptogenic - in
      55,2%. Cerebrovascular accidents were the most frequent cause of symptomatic
      epilepsy. The distinct feature of the cohort studied was the non-compliance
      recorded in a half of all patients. In the end of the study, 46,6% patients
      received carbamazepine, 34,5% - valproate, 24,1% - phenobarbital, 13,8% -
      topiramate, 3,4% - phenytoin, 1,7% - lamotrigine and 12,1% of patients did not
      use antiepileptic drugs. Clinical features, efficacy of diagnosis and treatment
      as well as reasons of non-compliance in elderly epileptic patients were described
      and analyzed.

PMID- 21947062
TI  - De novo generation of prion strains.
AB  - Prions are self-replicating proteins that can cause neurodegenerative disorders
      such as bovine spongiform encephalopathy (also known as mad cow disease).
      Aberrant conformations of prion proteins accumulate in the central nervous
      system, causing spongiform changes in the brain and eventually death. Since the
      inception of the prion hypothesis - which states that misfolded proteins are the
      infectious agents that cause these diseases - researchers have sought to generate
      infectious proteins from defined components in the laboratory with varying
      degrees of success. Here, we discuss several recent studies that have produced an
      array of novel prion strains in vitro that exhibit increasingly high titres of
      infectivity. These advances promise unprecedented insight into the structure of
      prions and the mechanisms by which they originate and propagate.

PMID- 21947065
TI  - [Differential aspects of multiple sclerosis and chronic borrelial
      encephalomyelitis].
AB  - The Yaroslavl region is an endemic area for Lyme disease (LD) with one of the
      highest levels of morbidity in Russia. Chronic neuroborreliosis can mimic
      multiple sclerosis and cause considerable difficulties in differential diagnosis.
      A comparative clinical-instrumental analysis of patients with definite multiple
      sclerosis (n=65) and chronic borrelial encephalomyelitis (n=11) was carried out.
      The key differential-diagnostic features of multiple sclerosis and borrelial
      encephalomyelitis were specified. Migrating erythema and tick's bite in the
      anamnesis, combined with lesions of the central and peripheral nervous systems,
      the absence of retrobulbar neuritis in the anamnesis, artralgia and myalgia, the
      high blood sedimentation rate were not characteristic of multiple sclerosis. A
      patient with abovementioned findings should be tested for the presence of
      antibodies to Borrelia burgdorferi in the blood serum and, if necessary, in the
      cerebrospinal fluid to exclude the diagnosis of Lime disease.

PMID- 21947066
TI  - [Clinical features of epilepsy in patients with a cerebral ischemic lesions].
AB  - The integral medical supervision of 320 patients with epileptic seizures
      developed in the cases of cerebral ischemic lesion revealed the predominance of
      focal epileptic seizures and cortical ischemic pathology, and the correlation
      between the time of the clinical manifestation of seizures and the stroke
      subtype. The critical significance of stenoses and occlusions and the reduction
      of cerebrovascular reactivity in the vertebro-basilar basin were observed in
      patients with epileptic seizures due to the brain ischemic lesion compared with
      patients of the control group.

PMID- 21947067
TI  - [Somatic-autonomic disturbances in different types of depression].
AB  - To reveal correlations between the structure of somatic-autonomic disorders and
      types of depression - melancholic, anxious, apathic authors studied 102 patients,
      aged from 20 to 50 years, with depression of mild (23 patients) or moderate (79)
      severity; 12 patients with bipolar affective disorder, 24 - with depressive
      episode, 66 - with recurrent depressive disorder. Hamilton depression scale,
      methods for study of somatic-autonomic disturbances and predominance of
      sympathicotonia or parasympathicotonia were used. Somatic-autoniomic disorders
      were presented in all types of depression, mostly in anxious depressions, lastly 
      in apathic depresions, melancholic depressions were in intermediate position.
      For each depression, common and specific somatic-autonomic disorders were found
      which correlated with type of leading affect and structure of depressive
      syndrome.

PMID- 21947068
TI  - [Psychiatric disorders in temporal lobe gliomas].
AB  - The rate of temporal lobe gliomas among all hemispheric gliomas is up to 1/3
      cases. Psychiatric disorders are typical for temporal lesions and could be a
      single manifestation of the disease. There is a rich variety of different
      psychopathologic and epileptic signs exactly in cases of temporal gliomas in
      comparison to tumors with other localizations. Authors studied psychiatric
      disorders in a statistically significant group of patients (140 cases) with
      temporal lobe tumors. Side, localization, histology of lesion and functional
      asymmetry of patients (right- or left-handers) were taken into account.
      Psychiatric disorders were found in 74% of patients, mainly in cases of
      glioblastoma. Psychopathologic symptoms were more typical for left-sided lesions.
      The frequency of  psychiatric disorders was significantly higher (p<0,05) in left
      handers compared to right-handers. After surgical removal of tumor, the frequency
      of psychiatric disorders didn't differ significantly (p<0,05) by 2 years follow
      up.

PMID- 21947069
TI  - [The role of the MAO-B inhibitor razagiline in the treatment of Parkinson's
      disease].
AB  - The features of the new selective MAO-B inhibitor razagiline (azilect) are
      reviewed against the background of latest advances in the field of treatment of
      Parkinson's disease (PD). The authors present the results of treatment of 20
      patients in the full-blown stage of disease (mean age of patients 61.4+/-7.0
      years). One of the objectives was to study the effect of razagiline on speech
      disorders in PD. A battery of scales was used to assess the global efficacy of
      treatment and the effect of the drug on the groups of symptoms. The high
      symptomatic effect of the drug used as monotherapy in early stages and in the
      combination with levodopa drugs in the full-blown stages of disease was revealed.
      It has been concluded that razagiline has a neuroprotective effect and modifies
      the course of PD. It exerts an effect on axial symptoms of PD: reduces speech
      disorders, postural instability, frequency of freezing episodes, severity of
      pharmacological dyskinesias.

PMID- 21947070
TI  - [Effect of reflex therapy on the dynamics of cognitive impairment in patients
      with chronic vertebrobasilar insufficiency].
AB  - Effectiveness of reflex therapy on the dynamics of cognitive impairment was
      assessed during the observation and treatment of 77 patients with chronic
      vertebrobasilar insufficiency. The inclusion of acupuncture and biodynamic
      correction in the complex therapy of patients with chronic vertebrobasilar
      insufficiency increases the effectiveness of integrated treatment compared with
      conventional therapy that was confirmed by neuropsychological studies of patients
      with discirculatory encephalopathy caused by vertebral pathology.

PMID- 21947071
TI  - [A comparative analysis on the efficacy of sumamigren in treatment menstrual and
      non-menstrual migraine attacks].
AB  - Based on the headache diaries, authors compared clinical presentations, degree of
      disability and efficacy of sumamigren (sumatriptan) in treatment menstrual and
      non-menstrual migraine attacks in 27 women (mean age 35 +/- 1.7 years). The
      diagnosis of menstrual-associated migraine was made in accordance with a
      supplement to the International Classification of Headache Disorders. 2nd
      edition. The clinical characteristics and degree of reduction of disability in
      menstrual and non-menstrual migraine attacks did not differ during the treatment.
      Efficacy of sumamigren was comparable in both types of attacks.

PMID- 21947072
TI  - [Changes in EEG and reaction time in the treatment of apathic depression].
AB  - The aim of the study was to reveal changes in the brain's functional state of
      patients with apathic depression, aged 20-51 years, during the treatment.
      Spectral parameters of background EEG as well as latencies of simple sensorimotor
      reaction and of two-alternative choice reaction to auditory stimuli have been
      analyzed. The complex reorganization of EEG spatial-frequency structure at the
      stage of pronounced clinical improvement was noticed. It included the EEG signs
      of the facilitation of inhibitory processes (seen as the increase of slow wave
      delta, theta-1 and theta-2 spectral power) mainly in frontal, central and
      temporal areas of the right hemisphere; the EEG signs of decreased activation of
      temporal areas (seen as the decrease of beta spectral power mainly in the right
      hemisphere), as well as the EEG signs of increased activation of anterior
      cortical areas by excitatory brain stem reticular structures (seen as the
      increase of beta spectral power in left frontal and central zones). The mean
      values of latencies of both simple sensorimotor reaction and of two-alternative
      choice reaction have been decreased as well. The data obtained are in line with
      contemporary views on the predominant role of the right hemisphere in the
      regulation of negative emotions and in the pathogenesis of depression.

PMID- 21947073
TI  - [Ultrastructural changes of skin arteries in patients with spontaneous cerebral
      artery dissection].
AB  - Spontaneous cerebral artery dissection is a common cause of ischemic stroke in
      young adults and children. Dissection is often related to arterial wall weakness
      the cause of which is unknown. An aim of the present paper was to carry out an
      electron microscopic study of skin arteries and arterioles in patients with
      ischemic stroke caused by cerebral artery dissection. Skin biopsy samples from 3
      patients (2 men and one women, 15, 25 and 43 years of age, respectively) were
      studied. Electron microscopy revealed changes of endothelial, smooth muscle cells
      and fibroblasts in the skin microvessels. These changes included the decrease in
      the number of mitochondria and their alterations (vacuolization, destruction of
      the cristae, the presence of the needle-shaped crystals and crystal-like
      inclusions) and swelling of the endoplasmic reticulum. Some of these changes were
      characteristic of mitochondrial diseases. The changes in the extracellular matrix
      (thickening of the subendothelial layer and deposition of microcalcificats) were
      also detected. It is assumed that the mitochondrial cytopathy found in the skin
      microvessels may be also present in large cerebral arteries. This could underlie
      dysplastic changes in the cerebral artery wall and predispose to its dissection.

PMID- 21947074
TI  - [Immunological markers of severity and outcome of traumatic brain injury].
AB  - A microscopic immunological study of cerebral spinal fluid (CSF) of 100 patients
      with traumatic brain injury (TBI) of different severity was carried out in the
      1st, 10th and 21st days after trauma. The content of antibodies to basic myelin
      protein (BMP) and phospholipids (PL) significantly differed from that in the
      control group (patients with soft tissue head injuries without TBI) and was
      significantly higher in patients with severe TBI. The level of antibodies to BMP
      in the CSF was strongly correlated with scores on the Glasgow Coma Scale in the
      1st day after TBI and the degree of recovery of neurological status in the 21st
      day. The level of antibodies to PL was strongly correlated with the severity of
      cytosis, content of CSF erythrocytes and proteins. The correlation between
      antibodies to BMP and antibodies to PL was weak. The different diagnostic value
      of antibodies to BMP and to PL in the most acute period of TBI was found. In
      conclusion, content of antibodies to BMP may be used as a marker of TBI severity
      and outcome while the significant elevation of antibodies to PL indicates the
      severity of vascular complications of trauma.

PMID- 21947075
TI  - [Meningoencephalitis associated with cytomegalovirus, Herpes simplex and
      Varicella-zoster virus infections].

PMID- 21947076
TI  - [Niemann-Pick disease, type C: an adult form with the prevalence of psychiatric
      presentations].

PMID- 21947077
TI  - [Effect of cytoflavin on the recovery of cognitive function after the cardias
      surgery with artificial blood circulation].

PMID- 21947078
TI  - [Antioxidant therapy in the treatment of minor and mild (predemential) cognitive
      impairments of different genesis].

PMID- 21947079
TI  - BAP31 and BiP are essential for dislocation of SV40 from the endoplasmic
      reticulum to the cytosol.
AB  - How non-enveloped viruses overcome host cell membranes is poorly understood.
      Here, we show that after endocytosis and transport to the endoplasmic reticulum
      (ER), but before crossing the ER membrane to the cytosol, incoming simian virus
      40 particles are structurally remodelled leading to exposure of the amino
      terminal sequence of the minor viral protein VP2. These hydrophobic sequences
      anchor the virus to membranes. A negatively charged residue, Glu 17, in the alpha
      helical, membrane-embedded peptide is essential for infection, most likely by
      introducing an 'irregularity' recognized by the ER-associated degradation (ERAD)
      system for membrane proteins. Using a siRNA-mediated screen, the lumenal
      chaperone BiP and the ER-membrane protein BAP31 (both involved in ERAD) were
      identified as being essential for infection. They co-localized with the virus in
      discrete foci and promoted its ER-to-cytosol dislocation. Virus-like particles
      devoid of VP2 failed to cross the membrane. The results demonstrated that ERAD
      factors assist virus transport across the ER membrane.

PMID- 21947080
TI  - SHARPIN is an endogenous inhibitor of beta1-integrin activation.
AB  - Regulated activation of integrins is critical for cell adhesion, motility and
      tissue homeostasis. Talin and kindlins activate beta1-integrins, but the
      counteracting inhibiting mechanisms are poorly defined. We identified SHARPIN as
      an important inactivator of beta1-integrins in an RNAi screen. SHARPIN inhibited
      beta1-integrin functions in human cancer cells and primary leukocytes.
      Fibroblasts, leukocytes and keratinocytes from SHARPIN-deficient mice exhibited
      increased beta1-integrin activity, which was fully rescued by re-expression of
      SHARPIN. We found that SHARPIN directly binds to a conserved cytoplasmic region
      of integrin alpha-subunits and inhibits recruitment of talin and kindlin to the
      integrin. Therefore, SHARPIN inhibits the critical switching of beta1-integrins
      from inactive to active conformations.

PMID- 21947081
TI  - MCPH1 regulates the neuroprogenitor division mode by coupling the centrosomal
      cycle with mitotic entry through the Chk1-Cdc25 pathway.
AB  - Primary microcephaly 1 is a neurodevelopmental disorder caused by mutations in
      the MCPH1 gene, whose product MCPH1 (also known as microcephalin and BRIT1)
      regulates DNA-damage response. Here we show that Mcph1 disruption in mice results
      in primary microcephaly, mimicking human MCPH1 symptoms, owing to a premature
      switching of neuroprogenitors from symmetric to asymmetric division. MCPH1
      deficiency abrogates the localization of Chk1 to centrosomes, causing premature
      Cdk1 activation and early mitotic entry, which uncouples mitosis and the
      centrosome cycle. This misorients the mitotic spindle alignment and shifts the
      division plane of neuroprogenitors, to bias neurogenic cell fate. Silencing
      Cdc25b, a centrosome substrate of Chk1, corrects MCPH1-deficiency-induced spindle
      misalignment and rescues the premature neurogenic production in Mcph1-knockout
      neocortex. Thus, MCPH1, through its function in the Chk1-Cdc25-Cdk1 pathway to
      couple the centrosome cycle with mitosis, is required for precise mitotic spindle
      orientation and thereby regulates the progenitor division mode to maintain brain
      size.

PMID- 21947083
TI  - Chromo-fluorogenic detection of aldehydes with a rhodamine based sensor featuring
      an intramolecular deoxylactam.
AB  - A chromogenic and fluorogenic detection of aldehydes was achieved via analyte
      triggered opening of the deoxylactam of N-(rhodamine B)-deoxylactam
      ethylenediamine (dRB-EDA). The utility of the sensor was demonstrated by
      fluorescent labeling of aldehyde-displaying sialoproteins on cell surfaces.

PMID- 21947082
TI  - USP15 is a deubiquitylating enzyme for receptor-activated SMADs.
AB  - The TGFbeta pathway is critical for embryonic development and adult tissue
      homeostasis. On ligand stimulation, TGFbeta and BMP receptors phosphorylate
      receptor-activated SMADs (R-SMADs), which then associate with SMAD4 to form a
      transcriptional complex that regulates gene expression through specific DNA
      recognition. Several ubiquitin ligases serve as inhibitors of R-SMADs, yet no
      deubiquitylating enzyme (DUB) for these molecules has so far been identified.
      This has left unexplored the possibility that ubiquitylation of R-SMADs is
      reversible and engaged in regulating SMAD function, in addition to degradation.
      Here we identify USP15 as a DUB for R-SMADs. USP15 is required for TGFbeta and
      BMP responses in mammalian cells and Xenopus embryos. At the biochemical level,
      USP15 primarily opposes R-SMAD monoubiquitylation, which targets the DNA-binding
      domains of R-SMADs and prevents promoter recognition. As such, USP15 is critical
      for the occupancy of endogenous target promoters by the SMAD complex. These data
      identify an additional layer of control by which the ubiquitin system regulates
      TGFbeta biology.

PMID- 21947085
TI  - Pilot study on combination of azacitidine and low-dose cytarabine for patients
      with refractory anemia with excess blast.
AB  - This study analyzed the outcomes of the combination of azacitidine and low-dose
      cytarabine in patients newly diagnosed with refractory anemia with excess blast
      (RAEB). Patients were treated with azacitidine 75 mg/m(2) for 7 days
      subcutaneously and cytarabine 20 mg/m(2) intravenously for 7 days every 28 days.
      The assigned regimen was repeated for two cycles, then the patients treated with
      azacytidine alone until progression or allogeneic stem cell transplantation (allo
      SCT). Eighteen patients with 5 RAEB-1 and 13 RAEB-2 were enrolled in the current
      study. After two cycles of the combination therapy, responses were achieved in
      nine patients (50.0%): four complete response (CR) (22.2%), one partial response
      (5.6%), two marrow-CR (11.1%), and two hematologic improvement (11.1%). Four
      patients (22.2%) progressed to acute leukemia during two cycles of the
      combination therapy. The 1-year overall survival (OS) was 87.5% for the early
      response group (responses at two cycles) and 0% for the late response group
      (responses at four cycles, p = 0.042). Plus, the median survival time was 476
      days (range, 37-718 days) for the early response group and 221 days (range, 193
      249 days) for the late response group. The 1-year OS was 100% for the patients
      who underwent allo-SCT and 73.4% for those without allo-SCT. In summary, the
      combination therapy showed promising response rate when compared to treatment
      with azacitidine alone. However, it was limited in terms of preventing leukemic
      transformation. Allo-SCT would seem to be the only available treatment that can
      alter disease progression.

PMID- 21947084
TI  - The role of lipoprotein receptors on the physiological function of APP.
AB  - In this review, we will primarily focus on the role of members of the low-density
      lipoprotein receptor (LDL-R) family that are involved in trafficking and
      processing of the amyloid precursor protein (APP). We will discuss the role of
      the LDL-receptor family members, low-density lipoprotein receptor-related protein
      1 (LRP1), LRP1b, apolipoprotein E receptor 2, sortilin-related receptor
      (SorLA/LR11) and megalin/LRP2 on the physiological function of APP and its
      cellular localization. Additionally, we will focus on adaptor proteins that have
      been shown to influence the physiological function of LDL-R family members in
      combination with APP processing. The results in this review emphasize that the
      physiological function of APP cannot be explained by the focus on the APP protein
      alone but rather in combination with various direct or indirect interaction
      partners within the cellular environment.

PMID- 21947086
TI  - Prevalence of C282Y, H63D, and S65C mutations in hereditary HFE-hemochromatosis
      gene in Lithuanian population.
AB  - HFE-hemochromatosis is a common autosomal recessive disease caused by HFE gene
      mutations and characterized as iron overload and failure of different organs. The
      aim of this study was to determine the prevalence of C282Y (c.845 G>A), H63D
      (c.187 C>G), and S65C (c.193A>T) alleles of HFE gene in the Lithuanian
      population. One thousand and eleven healthy blood donors of Lithuanian
      nationality were examined in four different ethnic Lithuanian regions to
      determine HFE gene alleles and genotype frequencies. The samples of DNA were
      analyzed for the presence of restriction fragment length polymorphism and
      validated by DNA sequencing. Among 1,011 blood donors tested, the frequency of
      C282Y, H63D, and S65C alleles were 2.6%, 15.9%, and 1.9%, respectively. One third
      of the tested subjects (n = 336) had at least one of the C282Y or H63D HFE gene
      mutations. The screening of Lithuanian blood donors has detected 13 (1.3%)
      subjects with a genotype C282Y/C282Y or C282Y/H63D responsible for the
      development of HFE-hemochromatosis. The prevalence of C282Y mutation was
      significantly higher among the inhabitants of Zemaitija (Somogitia) at the Baltic
      Sea area (5.9%) in comparison to the regions of continental part of Lithuania
      (2.4% in Dzukija, 2.3% in Aukstaitija, and 2% in Suvalkija, p < 0.05). These data
      support the hypothesis that the p.C282Y mutation originated from Scandinavia and
      spread with the Vikings along the Baltic Sea coast. The first epidemiological
      investigation of HFE gene mutations in ethnic Lithuanians showed that the
      frequencies of H63D, C282Y, and S65C of HFE gene alleles are similar to the other
      North-Eastern Europeans, especially in the Baltic region (Estonia, Latvia),
      Poland, and part of Russia (Moscow region).

PMID- 21947087
TI  - Oxidative stress and antioxidant capacity in sickle cell anaemia patients
      receiving different treatments and medications for different periods of time.
AB  - To evaluate, in a longitudinal study, the profile of lipid peroxidation and
      antioxidant capacity markers in sickle cell anaemia patients receiving different
      treatments and medication over different time periods. The three groups were:
      patients undergoing transfusion therapy and receiving iron chelator deferasirox
      (DFX group, n = 20); patients receiving deferasirox and hydroxyurea (DFX + HU
      group, n = 10), and patients receiving only folic acid (FA group, n = 15).
      Thiobarbituric acid-reactive substance (TBARS) assays and trolox-equivalent
      antioxidant capacity (TEAC) assays were evaluated during two different periods of
      analysis, T0 and T1 (after ~388 days). Higher FA group TBARS values were observed
      compared with the DFX + HU group (p = 0.016) at T0; and at T1, higher FA group
      TBARS values were also observed compared with both the DFX group (p = 0.003) and
      the DFX + HU group (p = 0.0002). No variation in TEAC values was seen between
      groups, at either T0 or T1. The mean values of TBARS and TEAC for both the DFX
      and DFX + HU groups decreased at T1. The antioxidant effects of HU and DFX were
      observed by through an increase in TEAC levels in DFX and DFX + HU groups when
      compared with those of normal subjects. Increased TEAC values were not recorded
      in the FA group, and lipid peroxidation was seen to decrease after DFX and HU
      use.

PMID- 21947088
TI  - Non-covalent interaction of dietary polyphenols with total plasma proteins of
      type II diabetes: molecular structure/property-affinity relationships.
AB  - The molecular structure/property-affinity relationships of dietary polyphenols
      non-covalently binding to total plasma proteins of type II diabetes (IIDTPP) were
      investigated by comparing the binding constants obtained from the fluorescence
      titration method. An additional methoxy group in flavonoids increased their
      binding affinities for IIDTPP by 1.38 to 15.85 times. The hydroxylation at the 4'
      position (Ring B) of flavonols and the 5 position (Ring A) of isoflavones
      weakened the binding affinities; however, hydroxylation at other positions on
      flavonoids slightly enhanced or little affected the binding affinities for
      IIDTPP. The glycosylation of flavonoids slightly decreased or little affected the
      affinities for IIDTPP by less than 1 order of magnitude. The hydrogenation of the
      C2[double bond, length as m-dash]C3 double bond of flavone, 6-hydroxyflavone, 6
      methoxyflavone and myricetin decreased the binding affinities. The galloylation
      of catechins significantly improved the binding affinities with IIDTPP
      approximately 10 to 1000 times. The esterification of gallic acid increased its
      binding affinity. The hydrophobic force played an important role in the binding
      interaction between polyphenols and IIDTPP.

PMID- 21947089
TI  - Palladium-catalyzed desulfitative C-arylation of a benzo[d]oxazole C-H bond with
      arene sulfonyl chlorides.
AB  - A palladium-catalyzed direct desulfitative C-arylation of a benzo[d]oxazole C-H
      bond with arene sulfonyl chlorides is described. The procedure tolerates halo,
      cyano, nitro, trifluoromethyl, acetyl and acetylamino groups on the phenyl ring
      of sulfonyl chlorides, providing the arylation products in moderate to good
      yields. It represents a practical and attractive alternative for the synthesis of
      2-aryl benzoxazoles.

PMID- 21947090
TI  - Hemispherectomy in pediatric patients with epilepsy: a study of 45 cases with
      special emphasis on epileptic syndromes.
AB  - OBJECTIVE: In this study we report the clinical outcomes of hemispherectomy for
      epilepsy in pediatric patients with special emphasis on the epileptic syndromes
      and their etiologies. MATERIAL AND METHODS: We retrospectively studied 45
      patients with medically refractory epilepsy with hemispheric lesions who
      underwent hemispherectomy at the "Hospital de Pediatria Prof. Dr. Juan P.
      Garrahan", Buenos Aires, Argentina between February 1990 and February 2010.
      Patients had been assessed using a standard protocol involving clinical,
      neuroradiological, neurophysiological, and neuropsychological teams. RESULTS:
      Twenty-seven males and 18 females with a mean age of 8.5 years (range, 2 months
      to 18 years) who underwent epilepsy surgery for refractory epilepsy were
      assessed. The mean time of follow-up was 9.5 years (range, 1 to 16 years). The
      following epileptic syndromes were recognized: West syndrome in 15 patients
      (33.5%), Rasmussen syndrome in 13 (29%), focal symptomatic epilepsy in 8 (17.5%),
      startle epilepsy in 6 (13.5%), Lennox-Gastaut syndrome in 2 (5%), and continuous
      spikes and waves during slow sleep in 1 (2%). The surgical specimens revealed
      malformations of cortical development in 18 patients (40%), Rasmussen
      encephalitis in 13 (29%), porencephalic lesions in 10 (22%), gliosis in 2 (4.4%),
      tumor in 1 (2.2%), and Sturge-Weber syndrome in 1 (2.2%). CONCLUSION: The outcome
      of hemispherectomy in pediatric patients is good for those with refractory
      epilepsies, such as West syndrome, Lennox-Gastaut syndrome, epileptic
      encephalopathy with continuous spikes and waves during slow sleep, and startle
      epilepsy arising from a hemispheric lesion associated with hemiplegia.

PMID- 21947091
TI  - Growth of human prostate cancer cells is significantly suppressed in vitro with
      sodium butyrate through apoptosis.
AB  - Histone deacetylase inhibitors (HDACis) have shown significant antiproliferative
      and apoptotic properties in various types of cancer cells, including prostate
      cancer cells, and are therefore being evaluated as a treatment modality. However,
      the mechanism by which sodium butyrate (SB) induces apoptosis is not completely
      understood. We focused on SB which exists in the intestine and is therefore
      expected to have less adverse effects. In this study, three prostate cancer cell
      lines (LNCaP, DU145 and PC-3) were treated in vitro with different concentrations
      of SB. Cell proliferation was studied by the XTT assay; cell cycle analysis and
      induction of apoptosis were studied by laser scanning cytometry. Western blot
      analysis was used to study p21, p27, CDK2, CDK4, CDK6, caspase-3, caspase-7, Fas,
      FADD, TRADD, Bcl-2 and Bax protein expression. SB inhibited cell growth and
      induced apoptosis in a concentration-dependent manner in human prostate cancer
      cells (LNCaP, DU145 and PC-3). Western blot analysis showed dose-dependent
      increases of p21 levels in DU145 and PC-3 cells, and dose-dependent decreases of
      CDK2, CDK4, CDK6 and procaspase-3 protein levels in all three prostate cancer
      cell lines. Bcl-xL was significantly down-regulated in DU145 cells, and Bcl-2 was
      significantly down-regulated in PC-3 and LNCaP cells. No significant changes were
      observed in procaspase-7, TRADD and Bax expression, although slight decreases in
      Fas and FADD expression were seen in all three prostate cancer cell lines.
      Analysis of cell morphology using laser scanning microscopy detected condensed
      and fragmented nuclei. In conclusion, SB induces G1 and G2 arrest by increasing
      p21 expression resulting in CDK2, CDK4 and CDK6 down-regulation. SB potently
      induced apoptosis, which was accompanied by DNA fragmentation, down-regulated Bcl
      2 in LNCaP and PC-3 cells, Bcl-xL in DU145 cells, and down-regulated procaspase
      3, but not procaspase-7, in these human prostate cancer cell lines. These results
      suggest that SB may serve as a new modality for the treatment of hormone
      refractory prostate cancer.

PMID- 21947092
TI  - Empirical antifungal treatment: a valid alternative for invasive fungal
      infection.
AB  - Empirical antifungal therapy refers to initiation of an antifungal agent at the
      first possible clinical evidence of fungal infection. It is frequently
      recommended in neutropenic high-risk hematological patients of invasive fungal
      infection in order to guarantee an early approach. An extensive review is made of
      therapeutic advances and scientific evidence in this setting. Specific
      recommendations for use and criteria for selection of antifungal agents are
      discussed.

PMID- 21947093
TI  - Side effects of benznidazole treatment in a cohort of patients with Chagas
      disease in non-endemic country.
AB  - Chagas disease is a disease endemic in Latin America, caused by the parasite
      Trypanosoma cruzi. Benznidazole is the most commonly used drug for the
      etiological treatment of the disease although its effectiveness varies according
      to the phase of the same and toxic side effects are frequent. This prospective
      study describes the side effects of benznidazole treatment of a cohort of 373
      chronic patients. Of these 40.2% presented adverse reactions. The most frequent
      side effect were dermatological reactions 32.4% (121 of 373) followed by
      digestive intolerance 9.1% (34 of 373). Surprisingly, three cases of migratory
      arthritis were observed. Patients treated with benznidazole must be followed up
      so that the long term incidence of side effects can be studied.

PMID- 21947094
TI  - In vitro activity of retapamulin against linezolid and methicillin-resistant
      Staphylococcus aureus isolates.
AB  - OBJECTIVES: To determine the in vitro activity of retapamulin and other topical
      antibiotics (mupirocin, bacitracin, and fusidic acid) usually employed for nasal
      decolonization, against methicillin-susceptible Staphylococcus aureus (MSSA),
      methicillin-resistant S. aureus (MRSA), and linezolid and methicillin-resistant
      S. aureus. METHODS: The minimum inhibitory concentrations (MICs) were determined
      on Mueller-Hinton agar according to the guidelines of the Clinical and Laboratory
      Standards Institute and of the European Committee for Antimicrobial
      Susceptibility Testing. Presence of the cfr gene in linezolid and methicillin
      resistant S. aureus isolates was detected using polymerase chain reaction.
      RESULTS: Retapamulin inhibited all the isolates of MSSA and MRSA at 0.125 mg/L,
      but the 18 linezolid-resistant-MRSA strains proved resistant, with MICs over 32
      mg/L. Most MSSA isolates (9/10) were susceptible to mupirocin with MICs under
      0.19 mg/L, although this value decreased to half against MRSA, and almost all
      linezolid-resistant MRSA (17/18) strains were resistant to mupirocin with an MIC
      range of between 8 mg/L and 28 mg/L. The MIC of fusidic acid increased
      substantially against linezolid-resistant MRSA, whereas that of bacitracin showed
      no differences. CONCLUSIONS: Retapamulin demonstrated excellent in vitro activity
      against MSSA and MRSA strains, but not against MRSA isolates harbouring the cfr
      gene. The results of this in vitro study support cut-off values for retapamulin
      of <= 0.5, 1, and >= 2 mg/L for susceptible, intermediate, and resistant strains,
      respectively.

PMID- 21947095
TI  - [Rapid identification and susceptibility testing of Gram-positive cocci in
      BacT/ALERT blood cultures by direct inoculation into the Vitek 2 system].
AB  - INTRODUCTION: To provide the clinician with early information about blood culture
      results allows a better prognosis and a reduced mortality rate of the patient
      with sepsis. In order to contribute to this aim, we performed a study for the
      identification and susceptibility profiling of positive blood cultures by direct
      inoculation into the automated Vitek 2 system. MATERIALS AND METHODS: Blood
      cultures of 57 patients with monomicrobial bacteriaemia due to gram-positive
      cocci were evaluated. Addition of saponin to the fluid from blood culture bottles
      was performed prior to the inoculation of Vitek 2 system cards. The same samples
      were also examined with the standard method starting from agar plate grown
      subcultures. RESULTS: Comparison between the results obtained with the standard
      method and the direct method revealed that 82% of the samples were correctly
      identified and that 97% of the isolates showed a concordant antimicrobial
      susceptibility profile for all drugs tested. Compared to the standard method, the
      very major error rate of the direct method was just 0.5%, the major error rate
      was 0.5%, and the minor error rate was 2%. CONCLUSION: These data suggest that
      addition of saponin to the fluid from blood culture bottles of the
      BacT/ALERT((r)) 3D before inoculation of the appropriate Vitek 2 cards leads to
      the rapid and reliable identification and susceptibility profiling of gram
      positive cocci in blood samples. Compared to the standard method, the direct
      method would reduce turnaround time by at least 24 hours.

PMID- 21947096
TI  - [Which is the best empirical treatment in patients with urethritis?].
AB  - OBJECTIVE: To know the best empirical treatment of urethritis in patients at the
      City Center of Madrid. METHODS: 2.021 urethral exudates were analyzed in men
      between January 2003-December 2007. In addition to the traditional cultures, it
      was determined the presence of Chlamydia trachomatis, Ureaplasma urealyticum,
      Mycoplasma hominis, Trichomonas vaginalis and Herpes simplex. The susceptibility
      of N.gonorrhoeae and Haemophilus spp was performed by disk diffusion method and
      U. urealyticum by Mycoplasma IST. RESULTS: The percentage of positive samples
      was: 30.6%. The most frequently isolated microorganisms were: U. urealyticum
      9.9%, N. gonorrhoeae 7.4%, C. trachomatis 5.1% and Haemophilus spp 3.8%. The
      resistance of N. gonorrhoeae in the first period was: penicillin 11.8%,
      tetracycline 5.9%, ciprofloxacin 8.8% and presence of betalactamase 11.8%. In the
      second period: penicillin 9.7%, amoxicillin/clavulanic acid 1.4%, tetracycline
      8.3%, ciprofloxacin 23.6% and presence of betalactamase 10.5%. Resistance to
      ciprofloxacin in non-MSM (men having sex with men) was 20% and in MSM 56.2%.
      Resistance of Haemophilus spp in the first period was: 38.2% ampicillin,
      amoxicillin/clavulanic acid 8.8%, clarithromycin 35.3%, cotrimoxazole 64.7%,
      cefuroxime 5.9%, ciprofloxacin 8.8%, tetracycline 12.1% and presence of
      betalactamase 26.5%. In the second period:presence of betalactamase 41.9%,
      ampicillin 53.1%, amoxicillin/clavulanic acid 9.4%, cefuroxime 9.4%,
      clarithromycin 18.7%, tetracycline 34.4%, ciprofloxacin 15.6%, and cotrimoxazole
      68.7%. Resistance of U. urealyticum was: ciprofloxacin 80.7%, ofloxacin 32.4%,
      erythromycin 17.5%, azithromycin 9.6%, tetracycline 3.5% and doxycycline 0.8%.
      CONCLUSIONS: N. gonorrhoeae showed a level of resistance to tetracycline and
      ciprofloxacin higher in the second period, being significant for ciprofloxacin.
      Quinolone resistance was higher in MSM. Haemophilus spp showed a level of
      resistance to ampicillin, ciprofloxacin and tetracycline higher in the second
      period, being significant for tetracycline. U.urealyticum showed high level of
      resistance to ciprofloxacin (80.7%)and ofloxacin (32.4%) and low level of
      resistance to doxycycline (0.8%) and tetracycline (3.5%).

PMID- 21947097
TI  - [Economic evaluation of interventions for infectious diseases in Spain:
      systematic review and comparative analysis].
AB  - BACKGROUND: There exists the need to evaluate interventions addressed to prevent,
      control and reduce the burden of the infectious diseases; being economic
      evaluation an instrument can help to allocate healthcare resources efficiently.
      In this context, we assessed the evolution of economic evaluation of
      interventions for infectious diseases published in Spain, as well as we compared
      their main methodological characteristics with those of the studies directed to
      other diseases. METHODS: Systematic review and comparative analysis calculating
      odds ratios (OR). Electronic searches for literature beetwen 1983 and 2008 were
      conducted in PubMed/MEDLINE, SCOPUS, ISI Web of Knowledge, CRD, IME e IBECS, and
      manually in specialized journals and technical reports. The following variables
      were identified to analyze the characteristics of the reports: journal and year
      of publication, intervention, type of study, design, perspective, type of costs,
      financing source, and decision-making recommendations. RESULTS: One-hundred and
      one studies were included in the review. The main characteristics of the reports
      were: cost-effectiveness analysis (n=56; 55.4%), treatments evaluations (n=60;
      59.4%) and the use of decision analysis and mathematical simulation models (n=63;
      62.4%). Economic evaluation studies of infectious diseases showed the following
      associations (compared to a cohort of studies of other disease conditions
      [n=376]): cost-benefit analysis (OR, 3.55; 95% confidence interval [CI], 1.63 to
      7.74), prevention (OR, 4.14; 95% CI, 2.49 to 6.90), and societal perspective (OR,
      2.55; 95% CI, 1.43 to 4.56). CONCLUSION: Although there is an increase in the
      number of economic evaluations of infectious diseases published during last
      decades, the studies showed heterogeneity in the quality of the information
      regarding methods of analysis and data sources.

PMID- 21947098
TI  - Usefulness of monitoring linezolid trough serum concentration in prolonged
      treatments.
AB  - Linezolid has proven valuable in musculoskeletal infections, however, failure and
      resistance have been described and toxicity is worrisome when more than 28 days
      are necessary. We describe the first 5 cases in whom linezolid trough serum
      concentrations were weekly measured and its relationship with clinical outcome
      and toxicity.

PMID- 21947099
TI  - [Pharmacoeconomic assessment of daptomycin as first-line therapy for bacteraemia
      and complicated skin and skin structure infections caused by gram-positive
      pathogens in Spain].
AB  - OBJECTIVE: To assess the efficiency of daptomycin as firstline therapy (D) versus
      daptomycin as salvage therapy after vancomycin (V->D ) or linezolid (L->D)
      failure in gram-positive bacteraemia and complicated skin and skin-structure
      infections (cSSTIs). METHODS: Cost-effectiveness analysis of 161 bacteraemia and
      84 cSSTIs patients comparing the above mentioned therapeutic alternatives was
      performed using the data from 27 Spanish hospitals involved in the EUCORE study.
      Direct medical costs were considered. Patients were observed from the first
      antibiotic dose for infection until either the end of daptomycin therapy or
      exitus. A multivariate Monte Carlo probabilistic sensitivity analysis was applied
      for costs (lognormal distribution) and effectiveness (normal distribution).
      RESULTS: In terms of effectiveness there were no statistical differences between
      groups but referring total costs per patient, there were significant differences.
      Sensitivity analysis confirmed that D dominates over L->D between 44.2%-62.1% of
      simulations in bacteraemia and between 48.2%-67.5% in cSSTIs. In comparison to V
      >D, D dominance was detected in 29.2%-33.2% of simulations in bacteraemia and
      between 48.2%-59.3% in cSSTIs. CONCLUSIONS: Daptomycin as first-line therapy
      dominates over daptomycin as salvage therapy after linezolid failure both in
      bacteraemia and cSSTIs. Comparing daptomycin as first-line therapy with its use
      after vancomycin failure, in cSSTIs the former is dominant. In bacteremia
      daptomycin as first line therapy is as effective as daptomycin as salvage therapy
      after vancomycin failure and implies lower costs.

PMID- 21947100
TI  - [Evaluation of a rapid test info immunochomatographic for detection of hepatitis
      B surface].

PMID- 21947101
TI  - [Fatal bacteremia caused by Campylobacter fetus and Campylobacter jejuni in
      patients with alcoholic liver disease].

PMID- 21947102
TI  - Invasive fungal infections in onco-haematology: a Spanish perspective.

PMID- 21947104
TI  - [The BASKET-PROVE study].

PMID- 21947103
TI  - Comparative high-resolution pQCT analysis of femoral neck indicates different
      bone mass distribution in osteoporosis and osteoarthritis.
AB  - SUMMARY: Osteoarthritis is linked to a reduced risk of femoral fracture despite
      osteoporosis. Different bone distribution in the femoral neck in osteoarthritis
      and fracture was revealed using a peripheral quantitative computed tomography
      (pQCT) comparative analysis. Our findings sustain the presence of an adaptive
      mechanism of bone structure providing fracture protection in osteoarthritis.
      INTRODUCTION: Although osteoarthritis is associated with reduced femoral fracture
      risk, it does not protect from bone loss. We investigated whether adaptive
      mechanisms are present at the arthritic joint, leading to reduced fracture risk,
      despite the presence of low bone mass density. METHODS: We performed pQCT
      comparative analyses of human femoral neck specimens derived from 32
      postmenopausal women who received hip prostheses for osteoarthritis (n = 19) or
      femoral fracture (n = 13) by applying an in-house automated software to extract
      bone structure descriptors, characterize trabecular and cortical bone
      distribution, and evaluate their mutual relationships. RESULTS: The cortical bone
      volume and trabecular thickness were significantly (p < 0.05) higher in the
      osteoarthritis group than in the fracture group. Trabecular bone volume was also
      significantly (p < 0.05) higher in the osteoarthritis group than the fracture
      group at the inferior and anterior quadrants. Significance was maintained after
      adjusting for age, cortical bone volume, and cortical porosity thickness.
      Multiple linear regression analysis showed that thickness, volume, and apparent
      density of the trabecular region significantly (p < 0.05) correlated with the
      same cortical descriptors in osteoarthritis, but no significant relationship was
      found in the fracture group. Age differentially affected the mutual relationships
      in the two groups, showing a significant correlation with trabecular thickness in
      both groups and with apparent trabecular density only in femoral fracture group.
      CONCLUSIONS: Starting from these differences in the structural descriptors, our
      study sustains the presence of a compensatory mechanism in osteoarthritis to
      preserve the mechanical competence of bone structure, despite the loss of
      trabecular bone, underlying lower fracture risk.

PMID- 21947105
TI  - [The RIVAL study].

PMID- 21947106
TI  - [Clinical value of inflammatory biomarkers after stent implantation].
AB  - The introduction of coronary stents into clinical practice has revolutionized the
      treatment of coronary artery disease. However, in-stent restenosis (ISR) and
      stent thrombosis represent the main adverse reactions following stent
      implantation. Along with procedural and technical factors, individual
      susceptibility, in particular the inflammatory response, play an important role
      in the development of these complications. C-reactive protein, one of the most
      extensively studied inflammatory biomarkers, was found to predict the risk of ISR
      but not of stent thrombosis in bare-metal stent (BMS)-treated patients. On the
      contrary, C-reactive protein failed to predict the occurrence of ISR in drug
      eluting stent (DES)-treated patients, but it appeared to predict the risk of
      stent thrombosis. Important differences in the pathophysiological mechanisms of
      adverse reactions to BMS and DES account for the differences in the prognostic
      value of inflammatory biomarkers. Moreover, DES polymers are responsible for late
      hypersensitivity allergic reactions that may lead to late ISR and stent
      thrombosis. Notably, a correct employment of inflammatory biomarkers may become a
      useful tool for identification and management of high-risk patients. In this
      review, the evolving role of inflammatory biomarkers in predicting adverse
      reactions after stent implantation is discussed, underlying therapeutic and
      clinical consequences for the management of patients receiving a BMS or a DES.

PMID- 21947107
TI  - [Role of pharmacologic or exercise stress echocardiography for the assessment of
      hemodynamics in valvular heart disease].
AB  - Stress echocardiography is emerging as an important component of stress testing
      in patients with valvular heart disease. Its role is not established in the
      routine assessment of patients, but its use is appealing for the possibility of
      objectively evaluating symptoms, hemodynamic changes, left ventricular function.
      Stress echocardiography has the advantages of being widely available, low cost
      and versatile for the assessment of disease severity. Nevertheless, there is a
      lack of convincing evidence that stress echocardiography may lead to clinical
      decisions and better outcomes. Therefore, large-scale prospective randomized
      studies focusing on patient outcomes are needed in the future.

PMID- 21947108
TI  - [Multimodality imaging in transcatheter aortic valve implantation procedures: the
      pivotal role of echocardiography].
AB  - Alternative percutaneous approaches to the management of symptomatic aortic
      stenosis in elderly and high-risk patients have become more attractive and raised
      profound interest in recent years. The superiority of transcatheter aortic valve
      implantation (TAVI) compared with medical therapy for patients deemed unsuitable
      for surgery has recently been established by the PARTNER trial, and preliminary
      randomized data in high-risk patients have confirmed that TAVI is non-inferior to
      surgical valve replacement in terms of safety and effectiveness. This finding
      will probably lead to an exponential increase in TAVI procedures over the next
      decade. In the clinical setting of the percutaneous approach, the choice of a
      specific valve is crucial to optimize the success rate and minimize the procedure
      related complications and requires accurate preprocedural diagnostic assessment.
      According to the high comorbidities of candidates currently undergoing a TAVI
      procedure, a tailored diagnostic framework in the elderly population is highly
      recommended. The present review discusses the role of echocardiography in the
      setting of multimodality imaging before the TAVI procedure and throughout the
      entire process, from patient selection to procedural guidance and post-procedural
      follow-up, suggesting a practical algorithm necessary for the best clinical
      outcome.

PMID- 21947109
TI  - [Feasibility and safety of same-day discharge after percutaneous coronary
      intervention with femoral access and AngioSeal closure device: a single-center
      experience].
AB  - BACKGROUND: Same-day discharge after coronary angiography or percutaneous
      coronary interventions (PCI) is safe. It allows a decrease in length of hospital
      stay, waiting list and operating expenses with increased patient satisfaction.
      The aim of this study was to evaluate the feasibility and safety of this approach
      in our center. METHODS: 798 selected patients considered suitable for same-day
      discharge were enrolled in our study and underwent coronary angiography and/or
      PCI procedures over a period of 5 years. All procedures were performed by femoral
      approach using the 6-8F AngioSeal closure device. A follow-up telephone interview
      was carried out in all patients after 7-10 days from discharge with particular
      regard to bleeding/vascular complications. RESULTS: After PCI procedures, 738
      patients (92.4%) were discharged as day cases. The remaining 60 patients (7.6%)
      were kept in hospital for longer observation. Procedural success was achieved in
      100% of patients. Hemostasis with the AngioSeal closure device was successfully
      obtained in 98.4% of cases. At follow-up, 6 patients developed mild size hematoma
      on femoral access site, without any other vascular complications or major
      bleeding needing blood transfusion. CONCLUSIONS: In our experience same-day
      discharge after coronary angiography or PCI was found to be feasible and safe in
      selected patients undergoing uncomplicated procedures performed by femoral
      approach using a closure device.

PMID- 21947110
TI  - [Transcatheter aortic valve implantation: are we ready? If so, for which
      patients? Is it sustainable? The clinical cardiologist's point of view].

PMID- 21947111
TI  - [Transcatheter aortic valve implantation: are we ready? If so, for which
      patients? Is it sustainable? The interventional cardiologist's point of view].

PMID- 21947112
TI  - [Transcatheter aortic valve implantation: are we ready? If so, for which
      patients? Is it sustainable? The cardiac surgeon's point of view].

PMID- 21947113
TI  - [Transradial coronary procedures in patients with high origin of the radial
      artery (axillary origin): two case reports and anatomical and technical
      considerations].
AB  - Background. Anatomical abnormalities (caliber and course) of radial artery are a
      potential limiting factor for diagnostic and interventional coronary procedures
      performed through the transradial approach. In these circumstances, prompt and
      careful angiographic assessment of the radial anatomy is crucial after sheath
      insertion in order to minimize the risk of vascular complications or access
      failure. Two case reports of a high origin of the radial artery (from the
      axillary artery) are described. After brief review of the anatomical
      classification of this abnormality, the different catheterization techniques to
      achieve procedural success and avoid switching to an alternative vascular access
      are discussed.

PMID- 21947114
TI  - [Stent thrombosis and clopidogrel response variability: is the genetic test
      useful in clinical practice?].
AB  - The antiplatelet agent clopidogrel is an effective drug for the prevention of
      thrombotic events in patients with acute coronary syndrome and in those
      undergoing percutaneous coronary intervention with the deployment of a coronary
      stent. However, it has been reported that, despite adequate treatment, about 30%
      of patients continue to show the high degree of platelet reactivity that is
      central to the development of atherothrombotic complications and poorer clinical
      outcomes. Up to 13% of those taking clopidogrel experience a recurrent ischemic
      event during the first year after acute coronary syndrome, 1-3% experience
      subacute stent thrombosis after percutaneous coronary intervention probably due
      to a poor drug response, and about 1.5% experience major bleeding mainly due to
      an enhanced response. Recent research findings have highlighted the role of
      genetic variations in determining antiplatelet response variability, and this has
      aroused interest in genotyping all thienopyridine-eligible patients in order to
      identify those who would be at increased risk of harm if treated with
      clopidogrel. However, it remains to be determined whether this information is
      necessary or sufficient for risk stratification. Only when there are clinical
      data to support the hypothesis that genotype-guided therapy reduces the rate of
      ischemic and bleeding events will it be possible to justify the use of genetic
      testing in all potential patients. When that happens, genotype-guided
      antiplatelet therapy will also be available in the field of cardiovascular
      medicine.

PMID- 21947115
TI  - [Goya's cardiac asthma].

PMID- 21947117
TI  - Hyperreninemic hypertension following presumed abdominal trauma.
AB  - BACKGROUND: An 18-year-old previously normotensive man was referred to a
      hypertension unit with blood pressure readings of 140-150/100-110 mmHg. Renal
      ultrasound had shown a right renal subcapsular fluid collection and an abdominal
      computed tomography scan had revealed a large cystic lesion surrounding the right
      kidney with a thick wall and irregular peripheral calcification consistent with a
      long-standing traumatic perinephric hematoma. INVESTIGATIONS: Physical
      examination, renal artery duplex ultrasonography, magnetic resonance imaging of
      the abdomen, isotopic renography with technetium-99m diethylenetriamine
      pentaacetic acid, and a renal venous renin ratio study. DIAGNOSIS: Hyperreninemic
      hypertension as a result of presumed abdominal trauma. MANAGEMENT: Removal of the
      affected kidney.

PMID- 21947116
TI  - Nutrition and growth in children with chronic kidney disease.
AB  - Poor growth in chronic kidney disease (CKD) is a marker of disease severity and
      of quality of care. Causes are multifactorial, and include malnutrition,
      cachexia, hematological factors, endocrine problems and metabolic abnormalities.
      In this Review, we focus on the impact of inadequate nutrition on growth
      disturbances in children with CKD, and discuss all aspects of the epidemiology,
      causes and potential treatments. Regional variations in resources may be a factor
      that contributes to the observed differences. Successful nutritional management
      requires a multidisciplinary team that includes not only doctors but also skilled
      nurses and dieticians. Extremes of body mass index, representing undernutrition
      and overnutrition, are associated with poor outcomes and should be avoided when
      designing therapeutic strategies for optimizing nutrition and growth in children
      with CKD. Improved understanding of the pathophysiology of cachexia and wasting
      in patients with CKD could lead to the development of novel therapeutic
      strategies.

PMID- 21947118
TI  - Peritoneal dialysis in children with end-stage renal disease.
AB  - Peritoneal dialysis is the preferred chronic dialysis modality for most children
      owing to its almost universal applicability and superior compatibility with
      lifestyle over other modalities. Although technological advances and increasing
      clinical experience have impacted favorably on patient and technique survival,
      clinical research in pediatric peritoneal dialysis has been hampered by the low
      incidence of end-stage renal disease (ESRD) in the pediatric population. To
      overcome this limitation, several international registries have emerged in the
      past few years to complement other long-standing registries, which together have
      provided useful information regarding technique-specific complications and
      comorbidities associated with ESRD in children undergoing chronic peritoneal
      dialysis. In this Review, we summarize the most relevant findings from these
      studies, highlighting the substantial variation in patient conditions, peritoneal
      dialysis practices and management of comorbidities encountered in different parts
      of the world.

PMID- 21947119
TI  - Dialysis: Dialysis modality and survival in ESRD--is the debate over?

PMID- 21947121
TI  - Therapy: Early plasma exchange may be beneficial in diarrhea-associated hemolytic
      uremic syndrome.

PMID- 21947120
TI  - Mineral and bone disorders in children with chronic kidney disease.
AB  - As children with chronic kidney disease (CKD) have a long lifespan, optimal
      control of bone and mineral homeostasis is essential not only for the prevention
      of debilitating skeletal complications and for achieving adequate growth but also
      for preserving long-term cardiovascular health. As the growing skeleton is highly
      dynamic and at particular risk of deterioration, close control of bone and
      mineral homeostasis is required in children with CKD. However, assessment of bone
      disease is hampered by the limited validity of biochemical parameters-major
      controversy exists on key issues such as parathyroid hormone target ranges and
      the lack of useful imaging techniques. The role of newly discovered factors in
      bone and mineral homeostasis, such as fibroblast growth factor 23, is not yet
      established. Even though scientific evidence is limited in children with CKD,
      ergocalciferol or cholecalciferol supplementation and the use of calcium-free
      phosphate binders is recommended. The new drug cinacalcet is highly promising;
      however, pediatric experience is still limited to observational data and the
      effect of cinacalcet on longitudinal growth and pubertal development is unknown.
      Randomized, controlled trials are underway, including studies of cinacalcet
      pharmacokinetics and pharmacodynamics in infants.

PMID- 21947122
TI  - The mechanism of hypocalciuria with NaCl cotransporter inhibition.
AB  - Thiazide diuretics are used to prevent the recurrence of calcium-containing
      kidney stones. The ability of these drugs to reduce urinary calcium excretion has
      a key role in this process. Although studies have shown a reduction in the
      recurrence rate of calcium-containing stones in patients treated with thiazides,
      whether hypocalciuria results from increased calcium reabsorption in the proximal
      or distal nephron is still unclear. When extracellular fluid volume is
      considerably reduced, the proximal tubule is likely to have a major role in
      thiazide-induced hypocalciuria. This process frequently occurs when high doses of
      thiazides and sodium restriction are prescribed for the treatment of kidney stone
      disease. The distal tubule is predominantly involved in NaCl cotransporter
      inhibition-induced hypocalciuria when the extracellular fluid volume is not
      reduced, a clinical scenario observed in patients with Gitelman syndrome. In this
      Perspectives article, we discuss the evidence supporting the hypocalciuric
      effects of NaCl cotransporter inhibition in the proximal and distal nephron.

PMID- 21947123
TI  - Definitive radiochemotherapy of advanced head and neck cancer with carboplatin
      and paclitaxel : a phase II study.
AB  - PURPOSE: To report outcome and toxicity of concurrent radiochemotherapy with
      carboplatin and paclitaxel in advanced squamous cell carcinomas of the oropharynx
      and hypopharynx. PATIENTS AND METHODS: Advanced inoperable carcinomas of the
      oropharynx and hypopharynx were treated with either hyper-fractionated,
      accelerated radiotherapy (50.0 Gy/2.0 with concomitant boost to 69.2 Gy/1.6) or
      conventional fractionated radiotherapy (70.2-72 Gy/1.8) concurrent with
      paclitaxel 40 mg/m2 and carboplatin AUC 1 weekly for 6 weeks. Acute and long-term
      toxicity was measured according to WHO- and CTC-criteria. RESULTS: A total of 84
      patients were included between 2000 and 2008. Median follow-up time of patients
      alive was 36 months. Conventionally fractionated radiotherapy was given to 16
      patients, while 68 patients were treated with concomitant boost. Finally, 88.1%
      of patients received full dose paclitaxel. Acute mucositis >= grade 3 was present
      in 51.2% of patients, while 6% of patients experienced >= grade 3 leucopenia and
      thrombopenia. A supportive gastric feeding tube was implanted in 89.1% of
      patients. Overall survival after 2 years was 46.3%, progression-free survival
      after 2 years was 41.0%. There was no significant survival difference between the
      different radiotherapy protocols. CONCLUSION: Concomitant carboplatin and
      paclitaxel is feasible and effective in advanced carcinomas of the head and neck.

PMID- 21947124
TI  - Accelerated radiotherapy with concomitant boost technique (69.5 Gy/5 weeks) : an
      alternative in the treatment of locally advanced head and neck cancer.
AB  - BACKGROUND AND PURPOSE: To present the feasibility and results of accelerated
      radiotherapy with concomitant boost technique (69.5 Gy/5 weeks) in the treatment
      of locally advanced head and neck cancer. PATIENTS AND METHODS: A total of 65
      patients were treated between June 2006 and August 2009. The distribution of
      clinical stages was as follows: II 11%, III 23%, IV 61%, and not defined 5%.
      RESULTS: The median follow-up was 30.5 months. The treatment plan was completed
      in 94% of patients. Patients were treated using the conformal or intensity
      modulated radiotherapy (IMRT) technique. The median overall treatment time was 37
      days (13-45 days). The mean radiotherapy dose was 68.4 Gy (16-74 Gy). Overall
      survival was 69% after 2 years. Disease-free survival was 62% after 2 years.
      Acute toxicity >= grade 3(RTOG scale) included mucositis (grade 3: 42.6%),
      pharynx (grade 3: 42.3%), skin (grade 3: 9.5%), larynx (grade 3: 4%), while late
      toxicity affected skin (grade 3: 6.25%) and salivary glands (grade 3: 3.7%).
      CONCLUSION: Accelerated radiotherapy with concomitant boost technique is feasible
      in patients with locally advanced head and neck cancer, has an acceptable
      toxicity profile, and yields promising treatment results.

PMID- 21947125
TI  - Practically acquired and modified cone-beam computed tomography images for
      accurate dose calculation in head and neck cancer.
AB  - BACKGROUND: On-line cone-beam computed tomography (CBCT) may be used to
      reconstruct the dose for geometric changes of patients and tumors during
      radiotherapy course. This study is to establish a practical method to modify the
      CBCT for accurate dose calculation in head and neck cancer. PATIENTS AND METHODS:
      Fan-beam CT (FBCT) and Elekta's CBCT were used to acquire images. The CT numbers
      for different materials on CBCT were mathematically modified to match them with
      FBCT. Three phantoms were scanned by FBCT and CBCT for image uniformity, spatial
      resolution, and CT numbers, and to compare the dose distribution from orthogonal
      beams. A Rando phantom was scanned and planned with intensity-modulated radiation
      therapy (IMRT). Finally, two nasopharyngeal cancer patients treated with IMRT had
      their CBCT image sets calculated for dose comparison. RESULTS: With 360 degrees 
      acquisition of CBCT and high-resolution reconstruction, the uniformity of CT
      number distribution was improved and the otherwise large variations for
      background and high-density materials were reduced significantly. The dose
      difference between FBCT and CBCT was < 2% in phantoms. In the Rando phantom and
      the patients, the dose-volume histograms were similar. The corresponding isodose
      curves covering >= 90% of prescribed dose on FBCT and CBCT were close to each
      other (within 2 mm). Most dosimetric differences were from the setup errors
      related to the interval changes in body shape and tumor response. CONCLUSION: The
      specific CBCT acquisition, reconstruction, and CT number modification can
      generate accurate dose calculation for the potential use in adaptive
      radiotherapy.

PMID- 21947127
TI  - Time-resolved predissociation of the vibrationless level of the B state of CH3I.
AB  - The predissociation dynamics of the vibrationless level of the first Rydberg 6s
      (B (1)E) state of CH(3)I has been studied by femtosecond-resolved velocity map
      imaging of both the CH(3) and I photofragments. The kinetic energy distributions
      of the two fragments have been recorded as a function of the pump-probe delay,
      and as a function of excitation within the umbrella and stretching vibrational
      modes of the CH(3) fragment. These observations are made by using (2 + 1)
      Resonant Enhanced MultiPhoton Ionization (REMPI) via the state of CH(3) to detect
      specific vibrational levels of CH(3). The vibrational branching fractions of the
      CH(3) are recovered by using the individual vibrationally state-selected CH(3)
      distributions to fit the kinetic energy distribution obtained by using
      nonresonant multiphoton ionization of either the I or the CH(3) fragment. The
      angular distributions and rise times of the two fragments differ significantly.
      These observations can be rationalized through a consideration of the alignment
      of the CH(3) fragment and the effect of this alignment on its detection
      efficiency. Two additional dissociation channels are detected: one associated
      with Rydberg states near 9.2 eV that were observed previously in photoelectron
      studies, and one associated with photodissociation of the parent cation around 15
      eV.

PMID- 21947126
TI  - Imaging of female pelvic malignancies regarding MRI, CT, and PET/CT : part 1.
AB  - AIM: The goal of this article is to provide an overview of diagnostic standard
      operating procedures for both clinical and imaging assessment of cervical and
      endometrial carcinoma, sarcoma of the uterus, and primary pelvic non-Hodgkin's
      lymphoma. METHODS: The literature was reviewed for methods used to diagnose
      malignancies in the female pelvis with a special focus on the role of MRI as the
      imaging method of choice. Furthermore, CT findings and staging criteria for the
      mentioned malignancies are also provided. CONCLUSION: Whereas ultrasound still
      remains the imaging modality of choice in clinical practice for the early
      diagnosis of female pelvic malignancies, MRI is more frequently recognized as a
      diagnostic tool for its accuracy in tumor identification. MRI also plays a
      crucial role in the 3D pretreatment planning for brachytherapy especially in
      cervical cancer. In the future, PET/CT might achieve an important role for
      staging lymph nodes or distant metastases as well as tumor recurrence.

PMID- 21947128
TI  - Stable radicals during photodecarbonylations of trityl-alkyl ketones enable solid
      state reactions through primary and secondary radical centers.
AB  - The solid state photoexcitation of several triphenylmethyl-alkyl ketones resulted
      in the loss of CO and the exclusive formation of radical-radical combination
      products. Differences in reactivity suggest a stepwise mechanism with the
      unprecedented formation of primary and secondary radicals in some of the radical
      pair intermediates in the solid state.

PMID- 21947129
TI  - Exploring High-D Spaces with Multiform Matrices and Small Multiples.
AB  - We introduce an approach to visual analysis of multivariate data that integrates
      several methods from information visualization, exploratory data analysis (EDA),
      and geovisualization. The approach leverages the component-based architecture
      implemented in GeoVISTA Studio to construct a flexible, multiview, tightly (but
      generically) coordinated, EDA toolkit. This toolkit builds upon traditional ideas
      behind both small multiples and scatterplot matrices in three fundamental ways.
      First, we develop a general, MultiForm, Bivariate Matrix and a complementary
      MultiForm, Bivariate Small Multiple plot in which different bivariate
      representation forms can be used in combination. We demonstrate the flexibility
      of this approach with matrices and small multiples that depict multivariate data
      through combinations of: scatterplots, bivariate maps, and space-filling
      displays. Second, we apply a measure of conditional entropy to (a) identify
      variables from a high-dimensional data set that are likely to display interesting
      relationships and (b) generate a default order of these variables in the matrix
      or small multiple display. Third, we add conditioning, a kind of dynamic
      query/filtering in which supplementary (undisplayed) variables are used to
      constrain the view onto variables that are displayed. Conditioning allows the
      effects of one or more well understood variables to be removed from the analysis,
      making relationships among remaining variables easier to explore. We illustrate
      the individual and combined functionality enabled by this approach through
      application to analysis of cancer diagnosis and mortality data and their
      associated covariates and risk factors.

PMID- 21947131
TI  - Selective particle trapping using an oscillating microbubble.
AB  - The ability to isolate and sort analytes within complex microfluidic volumes is
      essential to the success of lab-on-a-chip (LOC) devices. In this study,
      acoustically-excited oscillating bubbles are used to selectively trap particles,
      with the selectivity being a function of both particle size and density. The
      operating principle is based on the interplay between the strong microstreaming
      induced drag force and the attractive secondary Bjerknes force. Depending upon
      the size of the bubble, and thus its resonant frequency, it is possible to cause
      one force to dominate over the other, resulting in either particle attraction or
      repulsion. A theoretical analysis reveals the extent of the contribution of each
      force for a given particle size; in close agreement with experimental findings.
      Density-based trapping is also demonstrated, highlighting that denser particles
      experience a larger secondary Bjerknes force resulting in their attraction. This
      study showcases the excellent applicability and versatility of using oscillating
      bubbles as a trapping and sorting mechanism within LOC devices.

PMID- 21947130
TI  - Translational research of a novel humanized epidermal growth factor receptor
      related protein: a putative inhibitor of pan-ErbB.
AB  - PURPOSE: The ErbB family members are protein tyrosine kinases, which play a
      crucial role in the signal transduction pathways that regulate key cellular
      functions. Overexpression of the ErbB family members is associated with
      oncogenicity, metastatic potential, cell proliferation, apoptosis, angiogenesis,
      and prognosis in cancer. Molecular-targeted therapies centered on the ErbB
      signaling pathway are the currently promising anti-cancer therapies. METHODS: We
      reviewed the literature to summarize the current knowledge of epidermal growth
      factor receptor (EGFR)-related protein (ERRP) and determine the potential of this
      protein to be translated into a molecular-targeting treatment for cancer.
      RESULTS: ERRP isolated from rat gastroduodenal mucosa is a pan-ErbB inhibitor
      that targets multiple members of the ErbB family both in vitro and in vivo.
      Sequestration of ErbB ligands by ERRP results in the formation of inactive ErbB
      heterodimers and subsequent attenuation of signaling pathways activated by ErbB.
      We suggest a strategy to develop a humanized ERRP protein based on activity of
      rat EERP in vitro. CONCLUSIONS: As rat ERRP protein is expected to generate an
      immune response in humans, we propose a hypothesis that a humanized version of
      ERRP has potential therapeutic value for cancer patients.

PMID- 21947132
TI  - Preceding movement effects on sequential aiming.
AB  - In this study, two experiments were devised to examine the control strategy used
      by individuals when performing sequential aiming movements. Of particular
      interest was the aiming behavior displayed when task difficulty was changed
      midway through a sequence of movements. In Experiment 1, target size was
      manipulated, as the targets were made either larger or smaller, between the 8th
      and 12th movement of the sequence. In Experiment 2, the amplitude between the two
      targets was similarly changed while the target size remained constant. Results
      revealed that in Experiment 1, individuals took two movements following the
      perturbation to target size, to re-tune their movement times in order to
      correspond with the new task difficulty. Conversely for Experiment 2, movement
      time changed immediately and in correspondence with the new target amplitude.
      These findings demonstrate that participants can use information from the
      preceding movement to prepare and guide subsequent movements--but only when
      target size is changed. When response amplitude changes mid-sequence, it seems
      individuals rely more on immediate, target-derived information. Therefore,
      counter to some current accounts of visual movement control, it appears that
      memory representations of the preceding movement can guide subsequent movements;
      however, this information appears selectively accessed in a context-dependent
      fashion.

PMID- 21947133
TI  - Dynamic clicked surfaces based on functionalised pillar[5]arene.
AB  - A dynamic smart surface which was constructed by the self-assembly of an
      azobenzene-functionalised pillar[5]arene exhibits reversibly responsive
      morphologies towards UV and visible light as observed by TEM, SEM and AFM.

PMID- 21947134
TI  - [The late sodium current: pathophysiology and pharmacology of a new therapeutic
      target].
AB  - The sodium current (INa) plays a pivotal role in the propagation of electrical
      activity in the heart. However, a large body of evidence indicates that the
      "late" component of INa (INaL) may be enhanced in diseased myocardium. INaL
      enhancement has consequences on the electrical stability, contractile function
      and metabolism of cardiac myocytes, which may significantly contribute to disease
      progression. The possibility of blocking INaL selectively, that is to say without
      affecting the INa component involved in electrical propagation, has recently
      emerged. INaL has hence become a "therapeutic target", thus far clinically
      validated in the treatment of angina and arrhythmias but, as suggested by bench
      evidence, potentially relevant to a wider range of cardiac disorders. Such
      multiplicity of effects originates from the complex network of cell functions
      affected by INaL enhancement; acquaintance with such a network is useful in fully
      exploiting the therapeutic potential of selective INaL inhibition. This review
      deals with the pathophysiology of INaL enhancement and with the basic principles
      underlying its selective inhibition. Clinical evidence of antianginal and
      antiarrhythmic efficacy of INaL inhibition is available, but its discussion goes
      beyond the scope of this review.

PMID- 21947136
TI  - Modified laparoendoscopic gastrostomy tube (LEGT) placement.
AB  - PURPOSE: The purpose of this study was to report the outcomes of our modified
      LEGT technique. METHODS: Charts of 26 children who underwent modified LEGT
      technique between May 2008 and February 2010 were retrospectively reviewed. Their
      age ranged from 7 days to 16 years. Under general anesthesia, a gastroscope was
      placed in the stomach and laparoscopic visualization was obtained through a 5 mm
      umbilical port. Using laparoscopic and gastroscopic visualization, four 2'0' PDS
      'T'-Fasteners were placed around a proposed gastrostomy site in the stomach.
      These sutures were pulled externally and tied subcutaneously so that nothing was
      visible outside. The gastrostomy button was then placed in the center of these
      four sutures at the proposed gastrostomy button site. Once the gastrostomy
      balloon was inflated, the four sutures were pulled taut and tied subcutaneously
      to pexy the stomach to the abdominal wall. Visualization with the gastroscope and
      laparoscope ensured proper gastrostomy button placement. RESULTS: At a median
      follow-up of 9 months (range 10 days-2 years), none of the patients had major
      complications and only five had minor gastrostomy site infection which completely
      resolved after antibiotic therapy. CONCLUSIONS: LEGT is a safe and effective
      technique for placement of primary G buttons/tubes in children. The laparoscopic
      visualization of the LEGT avoids accidental gastro-enteric fistula formation and
      allows primary placement of the gastrostomy button without need for subsequent
      procedures. LEGT ensures that the G-button is placed within the gastric lumen.
      Additionally, the four 'T'-Fastener technique gives optimal fixation of the
      stomach to the abdominal wall, avoids accidental disruption of sutures as they
      are placed subcutaneously and has no need for suture removal at a post-operative
      visit as in other techniques. Since there are no other ports used except the
      umbilicus this technique provides excellent cosmetic results.

PMID- 21947135
TI  - How can we improve clinical trials in amyotrophic lateral sclerosis?
AB  - Since the approval of riluzole for the treatment of amyotrophic lateral sclerosis
      (ALS) 17 years ago, more than 30 large clinical trials have been conducted, but
      none has proved successful. The failure to translate positive preclinical results
      into the clinical setting raises questions about the validity of the rodent model
      that is used to study ALS, and about the quality of both preclinical and clinical
      studies. However, the greatest challenge is the disease itself as, with rare
      exceptions, the causes are unknown. In this Perspectives article, we highlight
      key issues related to the pathophysiology, preclinical studies and clinical
      trials that should be addressed in the future. These areas include the
      relationships between different disease mechanisms, the challenges presented by
      the heterogeneity of the disease, and the need for early intervention, optimal
      dose selection and effective biomarkers.

PMID- 21947138
TI  - Anticancer effects of a specific mixture of nutrients in the multidrug-resistant
      human uterine sarcoma MES-SA/Dx5 and the drug-sensitive MES-SA cell lines.
AB  - A specific nutrient mixture (NM) containing lysine, proline, ascorbic acid and
      green tea extract has demonstrated a broad spectrum of antitumor activity against
      a number of cancer cell lines. In this study, our main objective was to
      investigate the comparative effects of NM on anticancer parameters, such as
      cytotoxicity, matrix metalloproteinase (MMP) secretion and Matrigel invasion in
      the human uterine sarcoma drug-resistant MES-SA/Dx5 and the drug-sensitive MES-SA
      cell lines. In addition we studied the effects of NM on P-glycoprotein (Pgp) on
      these cell lines. Cell proliferation was evaluated by MTT assay, MMPs by
      gelatinase zymography, invasion through Matrigel, morphology by H&E and Pgp
      expression by Western blot analysis and immunodetection using FITC-conjugated
      antibody and rhodamine 123 (Rh123) accumulation and efflux assays. NM exhibited
      antiproliferative effects on MES-SA/Dx5, by 20% at 50 and 100 ug/ml and by 36, 40
      and 48% at 250, 500 and 1,000 ug/ml, respectively. By contrast, NM treatment of
      MES-SA cells resulted in significantly increased cytotoxicity: 40, 46, 65 and 72%
      at 50, 100, 500 and 1,000 ug/ml, respectively. In both cell lines, zymography
      demonstrated a band corresponding to MMP-2 in normal cells and MMP-9 with phorbol
      12-myristate 13-acetate treatment. The two MMPs showed dose-response inhibition
      by NM. As shown by Western blot analysis and immunodetection, NM treatment
      resulted in a dose-dependent decrease in Pgp expression in the MES-SA/Dx5 cell
      line. The MES-SA cell line does not exhibit Pgp. NM enhanced the accumulation and
      efflux of the Pgp substrate, Rh123, in the MES-SA/Dx5 uterine sarcoma cell line
      but not in the drug-sensitive cell line, MES-SA. Therefore, it can be concluded
      that NM demonstrates potent anticancer effects in both the drug-resistant and
      sensitive cell lines and modulates Pgp, suggesting its potential therapeutic
      effects in drug-resistant as well as sensitive cancers.

PMID- 21947137
TI  - Efficacy and safety of a novel delayed-release risedronate 35 mg once-a-week
      tablet.
AB  - Dosing regimens of oral bisphosphonates are inconvenient and contribute to poor
      compliance. The bone mineral density response to a once weekly delayed-release
      formulation of risedronate given before or following breakfast was non-inferior
      to traditional immediate-release risedronate given daily before breakfast.
      Delayed-release risedronate is a convenient regimen for oral bisphosphonate
      therapy. INTRODUCTION: We report the results of a randomized, controlled,
      clinical study assessing the efficacy and safety of a delayed-release (DR) 35 mg
      weekly oral formulation of risedronate that allows patients to take their weekly
      risedronate dose before or immediately after breakfast. METHODS: Women with
      postmenopausal osteoporosis were randomly assigned to receive risedronate 5 mg
      immediate-release (IR) daily (n = 307) at least 30 min before breakfast, or
      risedronate 35 mg DR weekly, either at least 30 min before breakfast (BB, n =
      308) or immediately following breakfast (FB, n = 307). Bone mineral density
      (BMD), bone turnover markers (BTMs), fractures, and adverse events were
      evaluated. The primary efficacy variable was percent change from baseline in
      lumbar spine BMD at Endpoint. RESULTS: Two hundred fifty-seven subjects (83.7%)
      in the IR daily group, 252 subjects (82.1%) in the DR FB weekly group, and 258
      subjects (83.8%) in the DR BB weekly group completed 1 year. Both DR weekly
      groups were determined to be non-inferior to the IR daily regimen. Mean percent
      changes in hip BMD were similar across groups. The magnitude of BTM response was
      similar across groups; some statistical differences were seen that were small and
      deemed by investigators to have no major clinical importance. The incidence of
      adverse events leading to withdrawal and serious adverse events were similar
      across treatment groups. All three regimens were well tolerated. CONCLUSIONS:
      Risedronate 35 mg DR weekly is similar in efficacy and safety to risedronate 5 mg
      IR daily, and will allow patients to take their weekly risedronate dose
      immediately after breakfast.

PMID- 21947139
TI  - Brugada pattern masking anterior myocardial infarction.
AB  - A middle-aged male smoker presented with atypical chest pain. Initial
      electrocardiogram (ECG) showed Brugada Type 1 pattern. Subsequent ECGs
      demonstrated evolving anterior ST elevation myocardial infarction (STEMI),
      consistent with the elevated cardiac enzymes. Coronary angiogram showed
      significant stenoses in the left anterior descending artery, which were stented
      emergently. In retrospect, subtle changes were noted in the initial ECG, which
      could have alerted one to the STEMI. However, the presence of a Brugada Type 1
      pattern masked the ECG changes of anterior STEMI and made the diagnosis
      difficult. A discussion of the literature surrounding Brugada syndrome is
      undertaken, including its clinical features, risk stratification and management.

PMID- 21947140
TI  - Medicine in stamps. Christiaan Eijkman (1858-1930): the vicar of vitamins.

PMID- 21947141
TI  - Guideline on training and credentialing in endoscopic retrograde
      cholangiopancreatography.
AB  - The aim of the Endoscopic Retrograde Cholangiopancreatography (ERCP) Working
      Group was to examine the issues of training, credentialing and quality control in
      ERCP in Singapore. Published guidelines and clinical trials concerning issues of
      training, complications and quality control in ERCP have been reviewed. The
      Working Group recommended that a trainee reach a minimum threshold of 200 cases
      before the assessment of competency. The target for achievement of competency was
      set at an 85 percent successful cannulation rate for native papilla. To perform
      advanced ERCP, endoscopists should have undergone dedicated training either in a
      recognised training centre or in conjunction with and under the guidance of a
      more experienced colleague, until technical competency is achieved. Precut should
      only be performed by endoscopists with experience and expertise in performing
      Levels II and III ERCP, who have been formally proctored. An audit of ERCP should
      examine parameters such as appropriate indication, success rates of selective
      cannulation, technical success rate of commonly performed procedures and
      procedure-related complications. To maintain technical competency, an individual
      should be performing ERCP on a regular basis. In conclusion, the innate risks of
      ERCP necessitate that all ERCP practitioners should be appropriately trained,
      practise within their expertise level and maintain regular practice in order to
      minimise risks and improve patient outcome.

PMID- 21947142
TI  - Treatment of scaphoid non-union with 1,2 intercompartmental supraretinacular
      artery (1,2 ICSRA) vascularised graft.
AB  - INTRODUCTION: The purpose of this paper is to share the outcome of cases of
      scaphoid non-union treated with 1,2 intercompartmental supraretinacular artery
      (1,2 ICSRA) vascularised graft at our institution, as well as to identify the
      possible factors for the failure of the procedure. METHODS: This was a
      retrospective review of 13 cases of scaphoid fracture non-union treated with 1,2
      ICSRA vascularised bone grafting from October 2000 to March 2003. A clinical and
      radiological review was conducted. Linear regression was performed in order to
      identify the factors associated with a negative outcome. RESULTS: Out of the 13
      patients with scaphoid non-union, ten (77 percent) had avascular necrosis of the
      proximal pole. The patients were followed up for a mean duration of 13 (range 3
      28) months. Ten out of the 13 (77 percent) patients achieved union. CONCLUSION:
      Our results are comparable to those reported by other studies and indicate that
      avascular necrosis was associated with failure to achieve union.

PMID- 21947143
TI  - Lower extremity amputation prevention in Singapore: economic analysis of results.
AB  - INTRODUCTION: The aim of the study was to determine the cost-effectiveness of the
      Lower Extremity Amputation Prevention (LEAP) strategy in comparison to standard
      clinical practice for treating patients with critical limb ischaemia (CLI).
      METHODS: A retrospective cost-effectiveness analysis of the LEAP programme
      relative to pre-LEAP practice was performed from the perspective of Singapore
      hospitals. The cost incorporated in the analysis included direct medical costs
      incurred during the admission. Outcomes included the number of amputations,
      number of deaths and length of hospital stay after the initial treatment.
      RESULTS: During the study period, the LEAP group had a lower amputation rate (29
      percent versus 76 percent, p-value is 0.00001), lower related death rate (one
      percent versus 19 percent, p-value is 0.00001) and fewer in-hospital days per
      patient (17.8 days versus 23.16 days, p-value is 0.048) as compared to the
      standard clinical practice group. The implementation of the LEAP strategy
      generated cost savings of S$2,566 per patient during admission when compared with
      the pre-LEAP approach. The results were robust to variations in input parameters.
      CONCLUSION: The LEAP strategy dominated standard practice in the management of
      patients with diabetes mellitus and CLI. The implementation of the LEAP strategy
      significantly improved patient outcomes and reduced hospital costs.

PMID- 21947144
TI  - Effects of monochromatic infrared energy therapy on diabetic feet with peripheral
      sensory neuropathy: a randomised controlled trial.
AB  - INTRODUCTION: Peripheral diabetic neuropathy, which is a cause of increasing
      morbidity and mortality following foot ulcers and amputations, is a burden to
      health and the economy. Various adjunct treatments to improve neuropathy have
      been introduced into the market; one such treatment is monochromatic infrared
      energy (MIRE) therapy, which claimed to produce promising results. This study
      aimed to evaluate the effects of MIRE on diabetic feet with peripheral
      neuropathy. METHODS: A randomised controlled, single-blinded study was conducted
      at Hospital Universiti Sains Malaysia from February 2008 to October 2008. A total
      of 30 feet from 24 patients were studied. Neuropathy was screened using the
      Michigan neuropathy scoring instrument, followed by an assessment of the current
      perception threshold using a neurometer at frequencies of 2,000 Hz, 250 Hz and 5
      Hz. The feet were randomised to receive either daily MIRE or sham treatment for a
      total of 12 treatments. Each foot was then reassessed using the neurometer at six
      weeks and three months following treatment. RESULTS: The data obtained was
      analysed using a non-parametric test to compare the pre- and post-treatment
      groups. No significant difference was found between the neuropathic foot of
      diabetic patients in both the MIRE and sham groups. CONCLUSION: No improvement of
      neuropathy was observed following MIRE treatment in the neuropathic feet of
      diabetic patients.

PMID- 21947145
TI  - Anatomical study of the distal end of cadaveric human ulnae: a clinical
      consideration for the management of distal radioulnar joint injuries.
AB  - INTRODUCTION: Detailed anatomical knowledge of the distal end of the ulna plays a
      pivotal role in understanding post-injury instability and painful conditions at
      the distal radioulnar joint (DRUJ), which can be due to avulsion of the ulnar
      styloid process or ulnar styloid triquetral impaction syndrome. With this in
      mind, data on the morphological features of distal ulnae in the Indian population
      was collected. METHODS: The distal end of 100 human ulnae (50 right-sided and 50
      left sided) of unknown gender from the anatomy department's bone bank were
      studied with regard to the seat (articular circumference of the head of ulna),
      ulnar styloid process, fovea and pole (articular surface for articulation of
      triangular fibrocartilaginous complex of the wrist on the head of ulna). RESULTS:
      The average length of the styloid process was 5.2 mm in the right-sided ulnae and
      5 mm in the left. The mean maximum height of the seat was noted to be 5.9 mm and
      6.9 mm on the right- and left-sided ulnae, respectively. The maximum width of the
      pole was calculated to be 5.4 mm (right-sided ulnae) and 6.1 mm (left-sided
      ulnae). The shapes of the pole and styloid process were also noted. Extensor
      carpi ulnaris groove was more commonly found on the left-sided ulnae. CONCLUSION:
      The study provides an anatomical database of the morphometry of parts of the
      distal end of the ulna in the Indian context, which will aid in the early
      management of DRUJ injuries.

PMID- 21947146
TI  - Densitometry trends in postmenopausal Asian women undergoing bisphosphonate
      treatment.
AB  - INTRODUCTION: Bisphosphonates have been shown to be effective in reducing the
      risk of fragility fractures in several landmark clinical trials conducted in
      Western populations. However, limited studies on bone mineral densitometry (BMD)
      trends have been conducted in Asian women. We conducted a retrospective review of
      electronic records to determine the actual BMD trends in a local population of
      postmenopausal women on bisphosphonate treatment. METHODS: The electronic records
      of all women over 50 years of age who had undergone BMD at Singapore General
      Hospital in 2004 were examined. Patients who were later started on
      bisphosphonates and continued the treatment for at least two years were selected
      for the study. Their subsequent BMD results were recorded, and longitudinal
      analysis was applied to determine the BMD trends as a cohort. RESULTS: A total of
      254 postmenopausal women were included for analysis. Their mean BMD T-score was 
      2.70 before treatment, and improved to -2.56 and -2.27 one and two years after
      treatment, respectively. However, the score deteriorated to -2.50 and -2.62 three
      and four years after treatment, respectively. The difference between each year's
      results and those of the baseline was statistically significant. CONCLUSION: In
      our study, the BMD scores in our local population showed improvement in the first
      two years of bisphosphonate treatment but declined subsequently. Our findings
      contrasted with those of studies conducted in Western populations. Further
      prospective studies are suggested so as to elucidate the actual BMD trends and
      fracture risk reduction in Asian women on bisphosphonate treatment.

PMID- 21947147
TI  - Reliability and accuracy of the tape measurement method with a nearest reading of
      5 mm in the assessment of leg length discrepancy.
AB  - INTRODUCTION: The aim of this study was to determine the reliability and accuracy
      of the tape measurement method (TMM) with a nearest reading of 5 mm in assessing
      leg length discrepancy (LLD). METHODS: This was a cross-sectional study conducted
      on 35 patients with LLD and 13 patients without LLD. Two blinded surgeons
      measured the lower limbs from the anterior superior iliac spine to the medial
      malleolus using TMM with a nearest reading of 5 mm. Computed tomography (CT)
      scanograms of the lower limbs of 22 patients were conducted by two blinded
      radiologists. Intraclass correlation coefficient (ICC) with 95 percent confidence
      interval was calculated to assess the interobserver reliability of TMM. The
      accuracy of TMM was assessed by comparison with CT as the gold standard. RESULTS:
      The interobserver reliability of LLD measurement using both TMM and CT scanogram
      was high, with ICCs of 0.924 and 0.971, respectively. No significant mean
      difference on paired sample t-test was observed for both TMM and CT scanogram.
      Compared to CT scanogram, TMM had good accuracy, with an ICC of 0.805. When the
      mean TMM readings by two observers were compared to those derived from CT
      scanogram, the ICC was found to be 0.847, with a mean difference of 1.95 (range 
      3.17 to 7.07) mm. CONCLUSION: There was excellent agreement in the LLD
      measurements between the two surgeons using TMM, between the two radiologists
      using CT sonogram, and between the TMM and CT measurements. This study showed
      that one TMM with the nearest reading of 5 mm was reliable and accurate in
      measuring LLD.

PMID- 21947148
TI  - Retinal changes in various altitude illnesses.
AB  - INTRODUCTION: This study aimed to evaluate the retinal changes associated with
      altitude illness in young soldiers. METHODS: A total of 50 young soldiers with
      altitude illness, who were referred to a tertiary care hospital between October
      2003 and January 2006, were included in the study. RESULTS: All the soldiers were
      male. The mean age of the subjects was 30.3 (range 20-44) years. Nine (18
      percent) soldiers had acute mountain sickness (AMS), nine (18 percent) had high
      altitude pulmonary oedema (HAPE) and 20 (40 percent) had high-altitude cerebral
      oedema (HACE). Retinal haemorrhages were observed in 29 soldiers (58 percent).
      Among these 29 cases, two also had symptoms of AMS, five had symptoms of HAPE and
      twelve had symptoms of HACE. High-altitude retinal haemorrhage alone as a sign of
      altitude illness was seen in ten cases. Severe grades of high-altitude
      retinopathy were found mostly in soldiers who suffered from HAPE and HACE. Visual
      recovery was complete in 22 (76 percent) soldiers. High-altitude retinal
      haemorrhage was associated with partial visual impairment in five (17 percent)
      soldiers and permanent visual loss in two (seven percent) soldiers. CONCLUSION:
      Retinal haemorrhages were noticed in 58 percent of soldiers with altitude
      illness. The association of severe grades of high-altitude retinopathy with HAPE
      and HACE was statistically significant. Branch retinal vein occlusion with
      macular oedema is an additional finding in our study, which has not been
      previously reported.

PMID- 21947149
TI  - A pilot study on domiciliary pulmonary rehabilitation programme in the management
      of severe chronic obstructive pulmonary disease.
AB  - INTRODUCTION: Pulmonary rehabilitation is now an accepted modality of care in the
      management of chronic obstructive pulmonary disease (COPD) patients. However, in
      resource-limited settings, conventional pulmonary rehabilitation may not be
      feasible due to the high cost involved and the extensive infrastructure
      requirement. In view of these constraints, we designed a domiciliary pulmonary
      rehabilitation programme and evaluated its usefulness in the management of severe
      COPD. METHODS: A total of 20 patients suffering from severe COPD (ten patients
      each in the experimental and control groups) were enrolled in the study. The
      experimental group was subjected to domiciliary pulmonary rehabilitation along
      with medical management, while the control group underwent only conventional
      medical management. During the six-month study period, both groups were assessed
      for quality of life (clinical COPD questionnaire), exercise capacity (six-minute
      walk distance) and spirometry values (forced expiratory volume in one second and
      forced vital capacity). RESULTS: Statistically significant differences were
      observed in clinical COPD questionnaire scores in both groups from the fourth
      month (p-value is 0.002 and 0.001 at the end of four and six months,
      respectively). The results of the six-minute walk distance showed a similar trend
      (p-value is 0.009 and 0.001 at the end of four and six months, respectively). No
      significant difference was observed in either of the spirometry values.
      CONCLUSION: The domiciliary pulmonary rehabilitation programme improves the
      quality of life and exercise endurance of patients with severe COPD, and thereby
      acts as a substitute for conventional pulmonary rehabilitation programmes in
      resource-limited situations.

PMID- 21947150
TI  - Clinics in diagnostic imaging (136). Chronic Schistosoma japonica infection of
      the liver.
AB  - A 37-year-old man from China was initially seen at the urology clinic for
      symptoms of urinary colic. Plain computed tomography (CT) imaging of the kidneys,
      ureters and bladder was performed, which (in addition to demonstrating renal
      calculi) revealed incidental findings of 'turtleback' septal and capsular
      calcifications, features pathognomonic for schistosomiasis japonica. Other
      classical features were demonstrated on the triphasic hepatic CT imaging that was
      subsequently performed. The clinical course, radiological features and
      complications of schistosomiasis japonica are discussed.

PMID- 21947151
TI  - Malaysia-ACCORD study: tip of the cardiovascular iceberg--we must do better.

PMID- 21947156
TI  - Mediastinal mass diagnosed as a benign schwannoma.
AB  - Neurogenic tumours of the mediastinum are most commonly present in the posterior
      mediastinal compartment. Schwannomas, being the most frequently encountered type,
      can be either benign or malignant, although the former is more common. They
      typically appear as an asymptomatic mass on radiographic imaging. These tumours
      with spindle-shaped cells are often asymptomatic, and are routinely detected on
      standard pulmonary radiography. However, computed tomography and magnetic
      resonance imaging, especially for posterior mediastinal tumours, provide
      additional information and help to determine its possible extension to adjacent
      structures. Therefore, radiographic and histopathological examinations are vital
      diagnostic tools in the detection of these silent tumours. Complete surgical
      resection using video-assisted thoracic surgical technique is the mainstay of
      treatment, and offers an excellent prognosis.

PMID- 21947157
TI  - Cytomegalovirus colitis in immunocompetent patients.
AB  - Cytomegalovirus (CMV) infection can present with severe manifestations that are
      associated with significant morbidity and mortality, especially in
      immunocompromised patients. CMV infections in immunocompetent patients are
      usually transient and do not exhibit many symptoms. However, in some patients,
      the manifestations can be severe. We report CMV colitis in two immunocompetent
      patients; one in a young man who was critically ill with septicaemia and
      significant non-bloody diarrhoea that responded to specific CMV treatment, and
      another in an elderly woman who presented with nonspecific abdominal pain and
      fever that resolved without specific CMV treatment.

PMID- 21947158
TI  - Primary thyroid lymphoma with elevated free thyroxine level.
AB  - Primary thyroid lymphoma (PTL) is a rare form of thyroid cancer that is known to
      be associated with Hashimoto thyroiditis. This association is supported by the
      presence of elevated titres of both antithyroglobulin and antimicrosomal
      antibodies in up to 95 percent of patients with PTL. Most patients with PTL
      present with a rapidly enlarging neck mass and compressive symptoms. The majority
      of thyroid cancer patients have normal levels of thyroid hormones; they are
      rarely hyperthyroid, with no obvious clinical features of thyrotoxicosis. We
      describe a patient who presented with minimal clinical features of thyrotoxicosis
      despite having markedly elevated serum free thyroxine and suppressed serum
      thyroid-stimulating hormone levels.

PMID- 21947159
TI  - Intestinal lymphangiectasia associated with recurrence of histiocytosis X.
AB  - Intestinal lymphangiectasia may occur as a primary congenital disorder or a
      secondary disorder. Secondary lymphangiectasia could be associated with diseases
      such as abdominal carcinoma, retroperitoneal fibrosis or chronic pancreatitis.
      This is the first reported case of intestinal lymphangiectasia associated with
      recurrent histiocytosis X. This case report illustrates the need for more
      prospective, well-designed studies to determine the natural history and outcome
      of intestinal lymphangiectasia in the duodenum. Hopefully, these studies will
      also help clinicians identify which group of patients with intestinal
      lymphangiectasia in the duodenum is more likely to have a secondary cause.

PMID- 21947160
TI  - Intracranial involvement in a patient with Hodgkin's lymphoma.
AB  - Intracranial and intraspinal involvement is a rare complication of Hodgkin's
      lymphoma. Intracranial involvement is observed in 0.2 to 0.5 percent of patients
      with Hodgkin's lymphoma. No specific risk factors associated with intracranial
      involvement have been found. We report intracranial involvement of Hodgkin's
      lymphoma in a patient who had previously undergone thyroidectomy due to thyroid
      papillary carcinoma.

PMID- 21947161
TI  - Use of radiosynovectomy in recurrent warfarin-related haemarthrosis in
      degenerative arthritis.
AB  - Radiosynovectomy is a local and minimally invasive radiotherapy for treating
      various chronic inflammatory arthritis such as rheumatoid arthritis,
      osteoarthritis and haemophilic arthropathy. In haemophilic arthropathy, it
      reduces the frequency of haemarthrosis and delays the development of severe joint
      destruction, which ultimately requires surgical intervention. Its role in
      warfarin-related haemarthrosis is less clear. Haemarthrosis is an uncommon
      complication of warfarin use, and anticoagulation may need to be discontinued. We
      describe yttrium-90 radiosynovectomy use in a 74-year-old man with underlying
      ischaemic heart disease, atrial fibrillation, previous embolic stroke and
      recurrent haemarthrosis of an osteoarthritic right knee. Anticoagulation was
      vital and could not be permanently stopped. Due to continuing anticoagulation, he
      had multiple hospitalisations with recurrent right knee haemarthrosis.
      Intraarticular right knee yttrium-90 citrate colloid injection led to a cessation
      of haemarthrosis for eight months. We examined the available literature for the
      role of radiosynovectomy in such circumstances.

PMID- 21947162
TI  - Constrictive pericarditis presenting as chylothorax.
AB  - Chylothorax is a rare clinical condition that can be attributed to a damaged
      thoracic duct. The condition is suggested by aspiration of milky white fluid from
      the pleural cavity and is commonly associated with either malignant diseases or
      trauma (e.g. cardiothoracic surgery). We present the case of a 15-year-old boy
      with chylothorax, whose effusion was due to constrictive pericarditis. The
      definitive treatment of chylothorax involves identification and management of the
      underlying pathology. We suggest that when dealing with cases of chylothorax,
      constrictive pericarditis should be considered among the causes.

PMID- 21947163
TI  - Chronic osteomyelitis in the lower extremity predisposing to the unusual
      formation of keloids.
AB  - Keloids commonly occur in black and pigmented races as well as in young adults,
      but rarely affect Caucasians and albinos. While they have a predilection for the
      upper trunk as well as the head and neck regions, they seldom occur in the lower
      limbs. A six-year-old boy presented with multiple fibrous nodular swellings of
      the right leg and a discharging sinus over the ankle. Closer evaluation revealed
      underlying chronic osteomyelitis complicated by multiple huge keloids over the
      leg and ankle. Associated chronic inflammation had resulted in the huge keloids.
      Our patient's age, site of occurrence and presentation were not typical. In the
      event that a keloid is presented in isolation, chronic osteomyelitis should be
      considered as a differential diagnosis, and a high index of suspicion is required
      in order to establish the diagnosis.

PMID- 21947164
TI  - Scrutinizing the effects of polarization in QM/MM excited state calculations.
AB  - In this paper we demonstrate the importance of including polarization-especially
      in a fully self-consistent-field manner-when calculating excited states within
      linear response QM/MM methods based on correlated electronic structure methods.
      We perform a systematic investigation of solvent polarization effects by
      identifying lower order polarization reaction fields as compared to the full
      treatment. In the process we highlight the different nature of static and dynamic
      reaction fields and demonstrate-by method of example on both solvated systems as
      well as on biomolecules-that inclusion of both of these is mandatory for an
      accurate description of excited states. Ultimately, these findings reflect the
      importance of the change in the solvent reaction field upon electronic
      excitations. In light of the recent increasing interest in excited state QM/MM
      methods incorporating mutual polarization between subsystems as a method for
      treating large molecular systems, the reported investigation constitutes an
      important step towards dissecting the accuracy of such calculations.

PMID- 21947166
TI  - Evaluation of the content coverage of SNOMED CT representing ICNP seven-axis
      version 1 concepts.
AB  - OBJECTIVES: The purpose of this study is to evaluate the ability of SNOMED CT
      (Systematized Nomenclature of Medicine Clinical Terms) to represent the concepts
      of the ICNP version 1--the seven-axis model. METHODS: The first author mapped
      1658 concepts of the ICNP version 1 to SNOMED CT using CLUE browser 5.0. The
      second author from SNOMED Terminology Solutions--with a team of SNOMED CT experts
      -and the third author from the ICN with a team of ICNP experts validated the
      mapping result. If there was any disagreement during the validation process, the
      three of us convened online meetings to reach a consensus. RESULTS: In total,
      SNOMED CT covered 1331 out of 1658 (80%) ICNP seven-axis model concepts ranging
      from a 61% coverage rate of the Actions Axis concepts to a 94% coverage rate of
      the Judgment axis concepts. CONCLUSIONS: SNOMED CT can represent most (80%) of
      the ICNP version 1 concepts. However, improvements in the ICNP version 1 in terms
      of concept naming and definition, and the addition of missing concepts to SNOMED
      CT, would lead to a greater harmonization of the ICNP seven-axis model version 1
      concepts with SNOMED CT.

PMID- 21947165
TI  - Differentially expressed genes in human peripheral blood as potential markers for
      statin response.
AB  - There is a considerable inter-individual variation in response to statin therapy
      and one third of patients do not meet their treatment goals. We aimed to identify
      differentially expressed genes that might be involved in the effects of statin
      treatment and to suggest potential markers to guide statin therapy. Forty-six
      healthy Korean subjects received atorvastatin; their whole-genome expression
      profiles in peripheral blood were analyzed before and after atorvastatin
      administration in relation with changes in lipid profiles. The expression
      patterns of the differentially expressed genes were also compared with the data
      of familial hypercholesterolemia (FH) patients and controls. Pairwise comparison
      analyses revealed differentially expressed genes involved in diverse biological
      processes and molecular functions related with immune responses. Atorvastain
      mainly affected antigen binding, immune or inflammatory response including
      interleukin pathways. Similar expression patterns of the genes were observed in
      patients with FH and controls. The Charcol-Leyden crystal (CLC), CCR2, CX3CR1,
      LRRN3, FOS, LDLR, HLA-DRB1, ERMN, and TCN1 genes were significantly associated
      with cholesterol levels or statin response. Interestingly, the CLC gene, which
      was significantly altered by atorvastatin administration and differentially
      expressed between FH patients and controls, showed much bigger change in high
      responsive group than in low-responsive group. We identified differentially
      expressed genes that might be involved in mechanisms underlying the known
      pleiotropic effects of atorvastatin, baseline cholesterol levels, and drug
      response. Our findings suggest CLC as a new candidate marker for statin response,
      and further validation is needed.

PMID- 21947167
TI  - Human yeast-specific CD8 T lymphocytes show a nonclassical effector molecule
      profile.
AB  - Pathogenic yeast and fungi represent a major group of human pathogens. The
      consequences of infections are diverse and range from local, clinically
      uncomplicated mycosis of the skin to systemic, life-threatening sepsis. Despite
      extensive MHC class I-restricted frequencies of yeast-specific CD8 T lymphocytes
      in healthy individuals and the essential role of the cell-mediated immunity in
      controlling infections, the characteristics and defense mechanisms of antifungal
      effector cells are still unclear. Here, we describe the direct analysis of yeast
      specific CD8 T lymphocytes in whole blood from healthy individuals. They show a
      unique, nonclassical phenotype expressing granulysin and granzyme K in lytic
      granules instead of the major effector molecules perforin and granzyme B. After
      stimulation in whole blood, yeast-specific CD8 T cells degranulated and, upon
      cultivation in the presence of IL-2, their granula were refilled with granulysin
      rather than with perforin and granzyme B. Moreover, yeast-specific stimulation
      through dendritic cells but not by yeast cells alone led to degranulation of the
      effector cells. As granulysin is the only effector molecule in lytic granules
      known to have antifungal properties, our data suggest yeast-specific CD8 T cells
      to be a nonclassical effector population whose antimicrobial effector machinery
      seems to be tailor-made for the efficient elimination of fungi as pathogens.

PMID- 21947168
TI  - Adjuvant therapy for resectable high-risk soft tissue sarcoma: feasibility and
      efficacy of a sandwich chemoradiotherapy strategy.
AB  - PURPOSE: Radical definitive surgery is the only curative treatment approach in
      resectable soft tissue sarcoma. Despite complete resection, patients with grade 2
      and 3 soft tissue sarcoma are at high risk of local or distant recurrence. Local
      and systemic adjuvant treatment includes radiotherapy and chemotherapy, but the
      optimal scheduling is not known. METHODS: In this phase II clinical trial, we
      combined surgery with adjuvant chemotherapy and radiotherapy in a novel
      trimodality treatment sequence. Two to 6 weeks after surgery, patients received 2
      cycles of chemotherapy containing doxorubicin and ifosfamide, then 50.4 Gy of
      percutaneous radiotherapy followed by additional 2 cycles of chemotherapy.
      RESULTS: Chemotherapy and radiotherapy-related toxicity was generally mild,
      without treatment delays in the majority of patients. After a median follow-up of
      57 months, 81.5% of patients are alive in complete remission. CONCLUSIONS: The
      sandwich chemoradiation protocol proved to be feasible with manageable toxicity.
      The patient outcome compared favorably with other adjuvant trials in preventing
      relapse, particularly distant relapse which is predictive of poor outcome. This
      multidisciplinary approach warrants further investigation in a larger randomized
      trial.

PMID- 21947169
TI  - Isolation of DNA aptamers using micro free flow electrophoresis.
AB  - A micro free flow electrophoresis (MUFFE) device was used to select DNA aptamers
      for human immunoglobulin E (IgE). The continuous nature of MUFFE allowed 1.8 *
      10(14) sequences to be introduced over a period of 30 min, a 300-fold improvement
      in library size over capillary electrophoresis based selections (CE-SELEX). Four
      rounds of selection were performed within four days. Aptamers with low nM
      dissociation constants for IgE were identified after a single round of MUFFE
      selection.

PMID- 21947171
TI  - Arousal, valence and their relative effects on postural control.
AB  - There is mounting evidence to suggest that emotional state can influence postural
      control. Emotions are often qualified using dimensions such as valence
      (pleasantness) and arousal. While affective pictures have been used to detail the
      effects of valence on postural control, the influence of arousal independently,
      or in combination with valence, has yet to be investigated. This is an important
      oversight because there are multiple sensory and neuromuscular mechanisms that
      are known to be sensitive to arousal and to contribute to postural control. As
      such, the current study is the first to independently manipulate valence and
      arousal through affective pictures and to examine their independent effects on
      postural control. Subjects stood quietly for 90 s long blocks while watching
      affective pictures, grouped by normative ratings of arousal (high and low) and
      valence (pleasant and unpleasant), and during which centre of pressure (COP) and
      electrodermal activity (EDA) were collected. EDA and anterior-posterior COP
      frequency were both increased with arousal, but not by valence. The postural
      effects observed in this study parallel those typically seen in other highly
      arousing situations, such as standing at the edge of an elevated platform or
      during performance evaluation. Therefore, we argue that arousal is a mediator of
      postural control and should be considered as a potential confound when testing or
      diagnosing subjects in clinical or experimental settings.

PMID- 21947170
TI  - N-acetylglucosamine-6-phosphate deacetylase (NagA) of Listeria monocytogenes EGD,
      an essential enzyme for the metabolism and recycling of amino sugars.
AB  - The main aim of our study was to determine the physiological function of NagA
      enzyme in the Listeria monocytogenes cell. The primary structure of the murein of
      L. monocytogenes is very similar to that of Escherichia coli, the main
      differences being amidation of diaminopimelic acid and partial de-N-acetylation
      of glucosamine residues. NagA is needed for the deacetylation of N-acetyl
      glucosamine-6 phosphate to glucosamine-6 phosphate and acetate. Analysis of the
      L. monocytogenes genome reveals the presence of two proteins with NagA domain,
      Lmo0956 and Lmo2108, which are cytoplasmic putative proteins. We introduced
      independent mutations into the structural genes for the two proteins. In-depth
      characterization of one of these mutants, MN1, deficient in protein Lmo0956
      revealed strikingly altered cell morphology, strongly reduced cell wall murein
      content and decreased sensitivity to cell wall hydrolase, mutanolysin and peptide
      antibiotic, colistin. The gene products of operon 150, consisting of three genes:
      lmo0956, lmo0957, and lmo0958, are necessary for the cytosolic steps of the amino
      sugar-recycling pathway. The cytoplasmic de-N-acetylase Lmo0956 of L.
      monocytogenes is required for cell wall peptidoglycan and teichoic acid
      biosynthesis and is also essential for bacterial cell growth, cell division, and
      sensitivity to cell wall hydrolases and peptide antibiotics.

PMID- 21947172
TI  - Observing human movements helps decoding environmental forces.
AB  - Vision of human actions can affect several features of visual motion processing,
      as well as the motor responses of the observer. Here, we tested the hypothesis
      that action observation helps decoding environmental forces during the
      interception of a decelerating target within a brief time window, a task
      intrinsically very difficult. We employed a factorial design to evaluate the
      effects of scene orientation (normal or inverted) and target gravity (normal or
      inverted). Button-press triggered the motion of a bullet, a piston, or a human
      arm. We found that the timing errors were smaller for upright scenes irrespective
      of gravity direction in the Bullet group, while the errors were smaller for the
      standard condition of normal scene and gravity in the Piston group. In the Arm
      group, instead, performance was better when the directions of scene and target
      gravity were concordant, irrespective of whether both were upright or inverted.
      These results suggest that the default viewer-centered reference frame is used
      with inanimate scenes, such as those of the Bullet and Piston protocols. Instead,
      the presence of biological movements in animate scenes (as in the Arm protocol)
      may help processing target kinematics under the ecological conditions of
      coherence between scene and target gravity directions.

PMID- 21947174
TI  - Self-touch affects motor imagery: a study on posture interference effect.
AB  - Several studies showed that mental rotation of body parts is interfered with by
      manipulation of the subjects' posture. However, the experimental manipulations in
      such studies, e.g., to hold one arm flexed on one's own chest, activated not only
      proprioceptive but also self-tactile information. Here, we tested the hypothesis
      that the combination of self-touch and proprioception is more effective than
      proprioception alone in interfering with motor imagery. In Experiment 1 right-
      and left-handers were required to perform the hand laterality task, while holding
      one arm (right or left) flexed with the hand in direct contact with their chest
      (self-touch condition, STC) or with the hand placed on a wooden smooth surface in
      correspondence with their chest (no self-touch condition, NoSTC); in a third
      neutral condition, subjects kept both arms extended (neutral posture condition,
      NPC). Right-handers were slower when judging hand laterality in STC with respect
      to NoSTC and NPC, particularly when the sensory manipulation involved their
      dominant arm. No posture-related effect was observed in left-handers. In
      Experiment 2, by applying the same sensory manipulations as above to both arms,
      we verified that previous results were not due to a conflict between perceived
      position of the two hands. These data highlighted a complex interaction between
      body schema and motor imagery, and underlined the role of hand dominance in
      shaping such interaction.

PMID- 21947173
TI  - Does orbital proprioception contribute to gaze stability during translation?
AB  - Translational motion induces retinal image slip which varies with object
      distance. The brain must know binocular eye position in real time in order to
      scale eye movements so as to minimize retinal slip. Two potential sources of eye
      position information are orbital proprioception and an internal representation of
      eye position derived from central ocular motor signals. To examine the role of
      orbital proprioceptive information, the position of the left eye was perturbed by
      microstimulation of the left abducens nerve during translational motion to the
      right or left along the interaural axis in two rhesus macaques. Microstimulation
      rotated the eye laterally, activating eye muscle proprioceptors, while keeping
      central motor commands undisturbed. We found that microstimulation-induced eye
      position changes did not affect the translational VOR in the abductive (lateral
      rectus) direction, but it did influence the responses in the adductive (medial
      rectus) direction. Our findings demonstrate that proprioceptive inputs appear to
      be involved in the TVOR responses at least during ipsilateral head movements and
      proprioceptive influences on the TVOR may involve vergence-related signals to the
      oculomotor nucleus. However, internal representation of eye position, derived
      from central ocular motor signals, likely plays the dominant role in providing
      eye position information for scaling eye movements during translational motion,
      particularly in the abducent direction.

PMID- 21947175
TI  - Benzimidazolyl functionalized ionic liquids as an additive for high performance
      dye-sensitized solar cells.
AB  - Benzimidazolyl functionalized ionic liquids were synthesized and applied as
      additives for dye-sensitized solar cells. The fabricated devices show an overall
      power conversion efficiency of ~7.79% under AM 1.5 radiation (50 mW cm(-2)), and
      an excellent long-term stability.

PMID- 21947176
TI  - Neutrophils in the pathogenesis and manifestations of SLE.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease of unclear etiology
      that affects mostly women of childbearing age. Profound abnormalities in both
      innate and adaptive immunity triggered by genetic and environmental factors are
      well documented to play an important part in the pathogenesis of SLE.
      Nonetheless, the role of neutrophils--the most abundant immune cell type--in the
      pathology of this disease has been unclear. Over the past decade, compelling
      evidence has emerged that implicates neutrophils in the initiation and
      perpetuation of SLE and also in the resultant organ damage frequently observed in
      patients with this disease. SLE-derived low-density granulocytes (LDGs) induce
      vascular damage and synthesize increased amounts of type I interferons and, as
      such, could play a prominent part in the pathogenesis of SLE. Furthermore,
      increased cell death and enhanced extracellular trap formation observed in SLE
      derived neutrophils might have key roles in the induction of autoimmunity and the
      development of organ damage in patients with SLE. Together, these events could
      have significant deleterious effects and promote aberrant immune responses in
      this disease. This Review highlights the role of neutrophils in the pathogenesis
      of SLE, with a particular focus on the putative deleterious effects of LDGs and
      neutrophil extracellular trap formation.

PMID- 21947179
TI  - Prediction of falling among stroke patients in rehabilitation.
AB  - OBJECTIVE: To identify risk factors and predict falling in stroke patients. To
      determine the strength of general vs mobility screening for this prediction.
      DESIGN: Prospective study. SUBJECTS: Patients in the first 6 months after stroke.
      METHODS: The following assessments were carried out: an interview concerning
      civil state and fall history, Mini-Mental State Examination, Geriatric Depression
      Scale, Falls Efficacy Scale (FES), Star Cancellation Task (SCT), Stroop test,
      Berg Balance Scale, Functional Ambulation Categories (FAC), Motricity Index, grip
      and quadriceps strength, Modified Ashworth Scale, Katz scale, and a 6-month fall
      follow-up. RESULTS: Sixty-five patients were included for analysis. Thirty -eight
      (58.5%) reported falling. Risk factors were: being single (odds ratio (OR) 4.7;
      95% confidence interval (95% CI) 1.2-18.3), SCT-time (OR 1.2; 95% CI 1.0-1.3),
      grip strength on unaffected side (US) (OR 0.1; 95% CI 0.0-0.8), FAC 3 vs FAC 4-5
      (OR 8.1; 95% CI 1.5-43.2), and walking aid vs none (OR 5.1; 95% CI 1.4-17.8).
      These parameters were included in predictive models, which finally implied a
      general model (I) with inclusion of SCT-time, FAC category and use of walking
      aid. A mobility model (II) included: FAC category and strength (US). These models
      showed a sensitivity of 94.1% and 76.3%, respectively. CONCLUSION: Several
      assessments and both prediction models showed acceptable accuracy in identifying
      fall-prone patients. A purely physical model can be used; however, looking beyond
      mobility aspects adds value. Further validation of these results is required.

PMID- 21947180
TI  - Past and present issues in Rasch analysis: the functional independence measure
      (FIMTM) revisited.
AB  - OBJECTIVE: To review the development of Rasch analysis by examining the history
      of its application to the Functional Independence Measure (FIMTM), and
      highlighting current issues in the approach. METHODS: All Rasch-based papers
      concerning the FIMTM were reviewed for their analytical strategy and results.
      Four analytical pathways were identified that accommodated the majority of these
      strategies. Data derived from secondary analysis of 340 in-patients undergoing
      rehabilitation following stroke, measured on the FIMTM Motor Scale, were fitted
      to the Rasch measurement model according to these 4 pathways, with 2 additional
      pathways to accommodate recent developments. RESULTS: In the analytical pathway,
      where items are not re-scored, the fit to the Partial Credit parameterization was
      better than the Rating Scale version. Fit improved following re-scoring of
      disordered thresholds. When local dependency was accommodated by 4 testlets, the
      Partial Credit, re-scored testlet version achieved adequate summary fit with no
      misfit among items, and unidimensionality. All other pathways required item
      deletion. CONCLUSION: The current study has shown that the FIMTM Motor Scale, as
      applied to a stroke rehabilitation sample, satisfies Rasch model expectations and
      the unidimensionality assumptions, having accommodated local dependency issues,
      and by using the partial credit parameterization with re-scored categories. Other
      analytical pathways gave less ideal solutions, and are consistent with the wide
      range of solutions found for the scale over the years. Consequently, the
      development of the Rasch approach in health outcomes can be traced in the history
      of analysis of the FIMTM, and that development continues to this day.

PMID- 21947181
TI  - Impaired postural control is associated with worse scores of the Health
      Assessment Questionnaire disability index among women with rheumatoid arthritis.
AB  - OBJECTIVE: To explore the relationship between functional status and different
      domains of postural control, and to make recommendations about the use of
      postural control tests in clinical practice among women with rheumatoid
      arthritis. SUBJECTS: A total of 91 women with rheumatoid arthritis and 110
      controls. The patients were grouped according to the total score of the Health
      Assessment Questionnaire (HAQ):HAQ1 = 0 (good, n = 21); HAQ2 = 0.1 to < 1
      (impaired, n = 44);HAQ3 = 1-3 (severely impaired, n = 26). METHODS: Postural
      control tests: timed one-leg stance test(OLST), timed up and go test (TUG), and
      posturography tests on a force-plate. RESULTS: A poorer performance in the OLST
      and TUG tests was associated with higher, i.e. worse, HAQ scores. The results of
      the force-plate measurements were more complex.The results for healthy controls
      provided some clarifying information,but did not alter the main results.
      CONCLUSION: It is recommended that both OLST and TUG tests are included in the
      postural control assessment design for patients with arthritis. It seems that the
      force-plate measurements are not as good for screening postural control
      impairments associated with functional disability, but they may still have their
      use in, for example, monitoring the effect of intervention or rehabilitation.

PMID- 21947177
TI  - Clinical features, pathogenesis and treatment of juvenile and adult
      dermatomyositis.
AB  - Juvenile and adult dermatomyositis (DM) have multiple commonalities, yet display
      differing prevalence of features, outcomes and comorbidities. In general,
      compared with the disease in adults, children with DM have more vasculopathy and
      a greater likelihood of calcinosis, periungual and gingival telangiectasias, and
      ulceration, but have a better long-term prognosis with improved survival. Adults
      with DM are more likely to have myositis-specific antibodies, develop
      interstitial lung disease, have amyopathic disease, and have a marked association
      with malignancy and other comorbidities. Both diseases have similar features on
      muscle biopsy and interferon gene signature, although subtle differences can
      exist in pathogenesis and pathology, such as more capillary loss and a greater
      degree of C5b-9 complement deposition in affected muscle of juvenile patients.
      Initiatives are underway to improve classification, markers of disease activity
      and ability to predict outcome of juvenile and adult DM. The purpose of this
      Review is to compare and contrast the unique features between juvenile and adult
      disease and to outline new initiatives in the field.

PMID- 21947178
TI  - Cartilage biology in osteoarthritis--lessons from developmental biology.
AB  - The cellular and molecular mechanisms responsible for the initiation and
      progression of osteoarthritis (OA), and in particular cartilage degeneration in
      OA, are not completely understood. Increasing evidence implicates developmental
      processes in OA etiology and pathogenesis. Herein, we review this evidence. We
      first examine subtle changes in cartilage development and the specification and
      formation of joints, which predispose to OA development, and second, we review
      the switch from an articular to a hypertrophic chondrocyte phenotype that is
      thought to be part of the OA pathological process ultimately resulting in
      cartilage degeneration. The latest studies are summarized and we discuss the
      concepts emerging from these findings in cartilage biology, in the light of our
      understanding of the developmental processes involved.

PMID- 21947182
TI  - Functional added value of microprocessor-controlled knee joints in daily life
      performance of Medicare Functional Classification Level-2 amputees.
AB  - OBJECTIVE: To assess the effects of using a microprocessor-controlled prosthetic
      knee joint on the functional performance of activities of daily living in persons
      with an above-knee leg amputation. OBJECTIVE: To assess the effects of using a
      microprocessor-controlled prosthetic knee joint on the functional performance of
      activities of daily living in persons with an above-knee leg amputation. DESIGN:
      Randomised cross-over trial. SUBJECTS: Forty-one persons with unilateral above
      knee or knee disarticulation limb loss, classified as Medicare Functional
      Classification Level-2 (MFCL-2). METHODS: Participants were measured in 3
      conditions, i.e. using a mechanically controlled knee joint and two types of
      microprocessor-controlled prosthetic knee joints. Functional performance level
      was assessed using a test in which participants performed 17 simulated activities
      of daily living (Assessment of Daily Activity Performance in Transfemoral
      amputees test). Performance time was measured and self-perceived level of
      difficulty was scored on a visual analogue scale for each activity. RESULTS: High
      levels of within-group variability in functional performance obscured detection
      of any effects of using a microprocessor-controlled prosthetic knee joint. Data
      analysis after stratification of the participants into 3 subgroups, i.e.
      participants with a "low", "intermediate" and "high" functional mobility level,
      showed that the two higher functional subgroups performed significantly faster
      using microprocessor-controlled prosthetic knee joints. CONCLUSION: MFCL-2
      amputees constitute a heterogeneous patient group with large variation in
      functional performance levels. A substantial part of this group seems to benefit
      from using a microprocessor-controlled prosthetic knee joint when performing
      activities of daily living.

PMID- 21947183
TI  - Coping with spinal cord injury: tenacious goal pursuit and flexible goal
      adjustment.
AB  - OBJECTIVE: To investigate the correlation of higher-order coping strategies of
      tenacious goal pursuit and flexible goal adjustment with adjustment after
      rehabilitation in spinal cord injury. DESIGN: Cross-sectional correlational
      study. SUBJECTS/PATIENTS: All 397 eligible patients entered for spinal cord
      rehabilitation between 1999 and 2009 were contacted and 130 (33%) agreed to
      complete a self-report questionnaire. METHODS: Partial correlations were computed
      between tenacious goal pursuit and flexible goal adjustment and affective and
      cognitive psychological adjustment. Demographics, spinal cord injury related
      variables, social support and coping were used as control variables. RESULTS:
      After controlling for relevant demographic, medical and social support indices,
      partial correlations between tenacious goal pursuit and indices of adaptation
      were not significant. Significant partial correlations were observed between
      flexible goal adjustment and each of the indices of adjustment (r = -0.33, -0.42,
      0.51, -0.38, respectively, for depression, anxiety, acceptance, and helplessness)
      after controlling for all relevant variables in the model. Flexible goal
      adjustment explained significant additional proportions of variance for each of
      the adjustment indices (7%, 11%, 18%, and 7%, respectively). CONCLUSION: Flexible
      goal adjustment, but not tenacious goal pursuit, is associated with psychological
      adjustment in spinal cord injury. Further research is needed to understand the
      mechanisms of flexible goal adjustment. Interventions targeting flexible goal
      adjustment might be of benefit for the patient.

PMID- 21947184
TI  - Effects of neurofeedback training with an electroencephalogram-based brain
      computer interface for hand paralysis in patients with chronic stroke: a
      preliminary case series study.
AB  - OBJECTIVE: To explore the effectiveness of neurorehabilitative training using an
      electroencephalogram-based brain- computer interface for hand paralysis following
      stroke. DESIGN: A case series study. SUBJECTS: Eight outpatients with chronic
      stroke demonstrating moderate to severe hemiparesis. METHODS: Based on analysis
      of volitionally decreased amplitudes of sensory motor rhythm during motor imagery
      involving extending the affected fingers, real-time visual feedback was provided.
      After successful motor imagery, a mechanical orthosis partially extended the
      fingers. Brain-computer interface interventions were carried out once or twice a
      week for a period of 4-7 months, and clinical and neurophysiological examinations
      pre- and post-intervention were compared. RESULTS: New voluntary
      electromyographic activity was measured in the affected finger extensors in 4
      cases who had little or no muscle activity before the training, and the other
      participants exhibited improvement in finger function. Significantly greater
      suppression of the sensory motor rhythm over both hemispheres was observed during
      motor imagery. Transcranial magnetic stimulation showed increased cortical
      excitability in the damaged hemisphere. Success rates of brain-computer interface
      training tended to increase as the session progressed in 4 cases. CONCLUSION:
      Brain-computer interface training appears to have yielded some improvement in
      motor function and brain plasticity. Further controlled research is needed to
      clarify the role of the brain-computer interface system.

PMID- 21947185
TI  - Shoulder measurements in the early period of ultrasound learning: chasing the
      butterfly?

PMID- 21947186
TI  - Down-regulation of HLA-A mRNA in peripheral blood mononuclear cell of colorectal
      cancer.
AB  - PURPOSE: It has been demonstrated that the alteration of human leukocyte antigen
      (HLA) class I expression frequently occurs in colorectal tumor. Previous studies
      mainly focused on the expression of HLA-A in tumor cells. The expression of HLA-A
      in peripheral blood mononuclear cells (PBMC) was unknown. To develop a non
      invasive diagnostic method for colorectal cancer (CRC), this work investigated
      the expression of HLA-A mRNA in PBMC in patients with CRC. METHODS: Real-time
      quantitative RT-PCR was used to study the expression of HLA-A mRNA in PBMC from
      48 patients with colorectal cancer, 38 patients with benign colorectal lesions,
      20 patients with rheumatoid arthritis, 20 patients with esophageal cancer and 40
      healthy individuals. Protein chip was utilized to detect the levels of serum CEA,
      CA 19-9, and CA 242 in all the cases. Overall results from the two methods were
      compared. RESULTS: The relative expression of HLA-A mRNA in PBMC was 1.11 +/-
      0.45 in healthy group, 0.81 +/- 0.42 in benign colorectal lesion group, and 0.39
      +/- 0.34 in cancer group, respectively. The diagnostic sensitivity of HLA-A mRNA,
      CEA, CA19-9, and CA242 was 81%, 59%, 61%, and 63%, and their diagnostic
      specificity was 75%, 64%, 52%, and 67%, respectively. CONCLUSIONS: The expression
      of HLA-A mRNA in PBMC from colorectal cancer group was significantly lower than
      those in both benign group and healthy group (P < 0.001). It could be potentially
      developed as a tumor assistant marker in future.

PMID- 21947187
TI  - [Coronary microvascular dysfunction. An update].
AB  - Several studies in the last years have shown that a dysfunction of coronary
      microcirculation may be responsible for abnormalities in coronary blood flow and
      some clinical pictures. Coronary microvascular dysfunction, in absence of other
      coronary artery abnormalities,  can cause anginal symptoms, resulting in a
      condition named microvascular angina (MVA). MVA can occur in a chronic form,
      predominantly related to effort (stable MVA), more frequently referred as cardiac
      syndrome X, or in an acute form, most frequently ensuing at rest, which simulates
      an acute coronary syndrome (unstable MVA).  The main abnormalities characterizing
      these two forms of MVA consist of an impaired vasodilation and an increased
      vasoconstriction of small resistive coronary arteries, respectively. The
      mechanisms responsible for stable MVA are still unclear, but seem to include,
      together with the known traditional cardiovascular risk factors, an abnormally
      increased cardiac adrenergic activity. The prognosis of stable MVA is good, but
      some patients have progressive worsening of symptoms. Clinical outcome of
      patients with unstable MVA is substantially unknown, as there are no specific
      studies about this population. Treatment of stable MVA includes traditional anti
      ischemic drugs as first step; in case of persisting symptoms several other drugs
      have been proposed, including xanthine derivatives, ACE-inhibitors, statins and,
      in women, estrogens. Severe forms of  intense constriction (or spasm) of small
      coronary arteries may cause transmural myocardial ischemia, as the microvascular
      form of variant angina and the tako-tsubo syndrome.

PMID- 21947188
TI  - [Non-traumatic chest pain. Work at the Chest Pain Unit of Umberto I Polyclinic in
      Rome].
AB  - The aim of the Chest Pain Unit at Policlinico Umberto I in Rome was to implement
      simple diagnostic flow-charts in subjects with non-traumatic chest pain for an
      early identification of patients at high, intermediate and low risk of acute
      coronary syndrome (ACS). A total of 4.74% of all patients admitted to the
      Emergency Department were hospitalized in the Chest Pain Unit. 15.72% of them
      received a diagnosis of atypical chest pain with low risk of ACS; 26,42% were
      diagnosed of stable angina pectoris; 11.37% were affected by chronic coronary
      heart disease with medium risk of ACS and 12.83% were at high risk of acute
      coronary syndrome.

PMID- 21947189
TI  - [Venous graft in-stent restanosis: diagnostic and treatment evolution].
AB  - This is the case of a 77 year-old man with previous coronary by-pass grafting.
      After the occlusion of the saphenous vein graft to marginal branch, corrected by
      angioplasty and stenting with a bare metal stent (BMS), during the next 4 years
      he experienced multiple further episodes of in-stent restenosis of the first BMS.
      Angioplasty was performed each time. After 4 months since the last procedure, he
      had new episode of unstable angina. An EKG-gated, 64-row multislice CT (MSCT)
      examination was performed to evaluate the venous graft lumen, showing high-grade
      in-stent restenosis. Angiography confirmed the MSCT diagnosis, thus he underwent
      angioplasty and stenting with a drug eluting stent (DES). Thereafter, he remained
      stable for 4 years, when new anginal episodes led to a further coronary
      angiogram, showing progression of the atherosclerosic disease at the proximal and
      distal anastomosis of the venous graft; however, the previous implanted DES was
      patent. In the complex management of venous grafts restenosis, MSCT can be useful
      to help in detecting obstructive bypass graft disease. When revascularization is
      needed, DES have shown to be superior compared to BMS.

PMID- 21947190
TI  - [A rare case of obstructive jaundice secondary to common hepatic artery
      aneurysm].
AB  - The common hepatic artery aneurysms (HAA) are uncommon atherosclerotic lesions
      and often they are clinically silent. Their diagnosis is often difficult prior to
      rupture, due to nonspecific clinical presentation. We report a case of a giant
      aneurysm of the common hepatic artery causing obstructive jaundice through
      compression of the biliary tract. The presence of the lesion was confirmed with
      the use of spiral computed tomographic angiography. Hepatic artery aneurysm is a
      lesion that should be considered in cases of unexplained obstructive jaundice.

PMID- 21947191
TI  - [A journey with Euterpe. Sinfonia concertante for music, heart and brain].
AB  - Unlike the Overlords, the highly cerebral alien beings of the Arthur Clarke's
      novel "Childhood's End", humans are strongly oriented toward music. Since the
      ancient cultures, the impact of music in eliciting physical and emotional
      reactions has been acknowledged, but its relationship with organic reactions has
      been mostly attributed to the domain of magic. Consistent experimental evidence
      shows that certain types of melody and rhythm might truly influence
      cardiovascular and neurophysiologic behaviours, while producing biochemical
      effects (e.g., reduction of stress), depending on the personal musical background
      of the listeners. As such, although the physiological basis is still poorly
      recognized, listening to the music has been proposed as a therapeutic for the
      treatment of a variety of disorders (the "Mozart effect"). This article, written
      in a "musical-like" form, provides a comprehensive analysis of reliable evidence
      supporting the influence of music on biochemistry and physiology, and concluding
      that the influence of music on human behaviours should be no longer confined to
      the realms of anecdote.

PMID- 21947192
TI  - [Osteoporosis associated with chronic obstructive pulmonary disease and other
      respiratory diseases].
AB  - Chronic obstructive pulmonary disease (COPD) and osteoporosis are associated
      because of common risk factors. In addition, COPD enhance systemic inflammation,
      vitamin D deficiency, and above all the use of systemic steroids induce bone
      destruction. Early prevention and treatment of osteoporosis is useful in COPD and
      in other chronic lung diseases.

PMID- 21947193
TI  - An International Survey-based Algorithm for the Pharmacologic Treatment of
      Obsessive-Compulsive Behaviors in Huntington's Disease.
AB  - It is generally believed that treatments are available to manage obsessive
      compulsive behaviors (OCB's) in Huntington's disease (HD). However, lack of an
      evidence base prevents guideline development. The research literature fails to
      address the indications for behavioral interventions, drug selection, drug
      dosing, management of inadequate response to a single drug, and preferred drugs
      when additional behavioral symptoms comorbid to OCBs are present. In an effort to
      inform clinical decision-making, we surveyed an international group of experts to
      address these points. Survey results showed that experts utilized behavioral
      therapy only for patients with mild cognitive impairment. There was expert
      agreement that a selective serotonin reuptake inhibitor (SSRI) was the first
      choice drug, although clomipramine (CMI) was cited as a monotherapy choice by the
      smaller number of experts familiar with its use. Perceived efficacy for control
      of OCBs was similar for both SSRIs and CMI. Though less favored choices overall,
      antipsychotics (APDs) and antiepileptic mood stabilizers (AEDs) were most often
      used as augmentation strategies. In addition to survey results, this report
      reviews available studies, and lastly presents an algorithm for the treatment of
      OCBs in HD based on practice-based preferences obtained from this survey.

PMID- 21947194
TI  - Effect of barley chromosome addition on the susceptibility of wheat to feeding by
      a gall-inducing leafhopper.
AB  - The maize orange leafhopper Cicadulina bipunctata is distributed widely in
      tropical and subtropical regions of the Old World and feeds on various Poaceae.
      The leafhopper is recognized as an important pest of maize in several countries.
      Adults as well as nymphs of C. bipunctata induce growth stunting and galls
      characterized by the severe swelling of leaf veins on many cereal crops including
      wheat, rice, and maize, but do not on barley. To clarify the mechanism of growth
      stunting and gall induction by C. bipunctata, we used six barley chromosome
      disomic addition lines of wheat (2H-7H) and investigated the effect of barley
      (cv. Betzes) chromosome addition on the susceptibility of wheat (cv. Chinese
      Spring) to feeding by the leafhopper. Feeding by C. bipunctata significantly
      stunted the growth in 2H, 3H, 4H, and 5H, but did not in 6H and 7H. The degree of
      gall induction was significantly weaker and severer in 3H and 5H than in Chinese
      Spring, respectively. These results suggest that barley genes resistant to growth
      stunting and gall induction exist in 6H and 7H, and 3H, respectively. 5H is
      considered to be useful for future assays investigating the mechanism of gall
      induction by this leafhopper because of the high susceptibility to the feeding by
      C. bipunctata. Significant correlation between the degrees of growth stunting and
      gall induction was not detected in the six chromosome addition lines and Chinese
      spring. This implies that these two symptoms are independent phenomena although
      both are initiated by the feeding of C. bipunctata.

PMID- 21947195
TI  - Serotonin-induced mate rejection in the female cabbage butterfly, Pieris rapae
      crucivora.
AB  - Virgin female cabbage butterflies, Pieris rapae crucivora, accept and mate with
      courting males, whereas mated females reject them and assume the "mate refusal
      posture". This study tested whether the biogenic amines, serotonin (5HT),
      dopamine (DA), and octopamine (OA), were responsible for this change in behavior.
      The results showed that 2-3-day-old virgin females fed with 5HT rejected courting
      males significantly more frequently compared with controls fed on sucrose. In
      contrast, the proportions of courting males rejected by virgin females fed with
      either DA or OA did not differ from sucrose-fed controls. Oral application of
      each amine resulted in significantly increased levels of the amine applied (or
      its metabolite) in the brain. The results strongly suggest that 5HT or a 5HT
      metabolite may be responsible for the post-mating change in behavioral response
      of 2-3-day-old virgin females to courting males. Similar effects of 5HT treatment
      were observed in 6-8-day-old virgin females, but in this case the results were
      only marginally different from the controls, suggesting that the effect may
      decline with increasing female age.

PMID- 21947196
TI  - Association of soluble apoptotic markers with impaired left ventricular
      deformation in patients with rheumatoid arthritis. Effects of inhibition of
      interleukin-1 activity by anakinra.
AB  - Myocardial function is impaired in rheumatoid arthritis (RA). Inhibition of
      interleukin (IL)-1 activity reduces experimental myocardial infarction by
      limiting apoptosis. We investigated whether a) soluble apoptotic markers are
      related with impaired left ventricular (LV) performance and b) treatment with
      anakinra, an IL-1 receptor antagonist, reduces apoptotic markers leading to
      improved LV performance in RA. We studied 46 RA patients. In an acute, double
      blind cross-over trial, 23 patients were randomised to a single injection of
      anakinra or placebo and after 48 hours (h) to the alternative treatment. In a
      chronic trial, 23 patients who received anakinra for 30 days were compared with
      23 patients who received prednisolone. At baseline, 3 h and 30 days after
      treatment, we measured circulating IL-1beta, tumour necrosis factor (TNF)-alpha,
      Fas, Fas-ligand and caspase-9 to assess apoptosis. At baseline and 30 days after
      treatment, we assessed LV longitudinal strain, strain rate and E/Em ratio using
      2D-speckle tracking and tissue Doppler echocardiography. At baseline, increased
      apoptotic markers were related with reduced LongSRS and increased E/Em (p<0.05).
      After 3 h and 30 days of anakinra, there was a reduction in Fas (median 481 vs.
      364 vs. 301 pg/ml), Fas-ligand (median 289 vs. 221 vs. 190 pg/ml), caspase-9
      (median 1.90 vs. 1.40 vs. 1.07 ng/ml), TNF-alpha and IL-1beta (p<0.05 for all
      comparisons). E/Em, LongS and LongSRS were improved after anakinra (p<0.01) and
      their percent changes were related with the corresponding changes of Fas and
      caspase-9 (p<0.05). No changes of the examined parameters were observed after
      prednisolone. In conclusion, inhibition of IL-1 activity by anakinra reduces
      apoptotic markers leading to improved LV performance in RA.

PMID- 21947197
TI  - Volvulus as a complication of chronic intestinal pseudo-obstruction syndrome.
AB  - Chronic intestinal pseudo-obstruction syndrome (CIPS) is a severe motility
      disorder of the gastrointestinal tract that presents with continuous or recurrent
      symptoms and signs of intestinal obstruction without evidence of a structural
      lesion occluding the intestinal lumen. Mechanical obstruction might occur in
      these patients as well but is typically difficult to distinguish from an
      exacerbation of CIPS. We report two pediatric cases in which mechanical
      obstruction by volvulus mimicked an exacerbation of CIPS, requiring surgical
      intervention. CONCLUSION: Awareness of the possibility of true mechanical
      obstruction in CIPS patients during an exacerbation episode is needed, as this is
      a severe condition and usually requires surgical intervention.

PMID- 21947198
TI  - Eponym: Barth syndrome.
AB  - Barth syndrome (OMIM #302060) (BTHS) is an X-linked disorder of lipid metabolism
      characterized by skeletal myopathy, neutropenia, growth delay, and
      cardiomyopathy. It is caused by mutations in the tafazzin gene (TAZ), which lead
      to decreased production of an enzyme required to produce cardiolipin, a component
      of the inner mitochondrial membrane necessary for proper functioning of the
      electron transport chain. The most common initial presentation of BTHS is
      significant heart failure due to cardiomyopathy, which is the main cause of death
      in infancy or childhood. On the other hand, some patients have limited clinical
      features of BTHS. These patients may be overlooked or misdiagnosed with
      unclassified congenital myopathy, especially when heart failure is not clinically
      significant. However, these patients could also develop significant heart failure
      or life-threatening arrhythmias during or even after childhood. Heart failure in
      BTHS is often responsive to standard medical therapy, indicating early diagnosis
      is critical. Diagnostic clues of BTHS in the subclinical stage of heart failure
      include family histories, findings of lipid storage myopathy in the skeletal
      muscle biopsy, and elevated plasma brain natriuretic peptide levels. The genetic
      analysis of TAZ is the only confirmatory method for the diagnosis of BTHS.
      CONCLUSION: physicians should be aware of the possibility of this disease and
      carry out genetic studies when it is considered.

PMID- 21947199
TI  - Using Clar sextets for two- and three-dimensional aromatic systems.
AB  - After a brief history of the aromaticity concept, the use of Clar sextet circles
      is reviewed for explaining various aspects of planar aromatic systems
      (benzenoids, heterocycles) and of tridimensional carbon aggregates. When folding
      a graphene sheet for obtaining nanotubes, nanotori, or nanocones, the congruence
      of Clar sextet circles allows the classification of all such aggregates into two
      classes (congruent or incongruent) with marked differences in properties; this is
      in agreement with the well-known condition h - k = 0 (mod 3), equivalent to
      congruence, in terms of the chiral vectors h and k for graphene sheets.

PMID- 21947200
TI  - RNAspace.org: An integrated environment for the prediction, annotation, and
      analysis of ncRNA.
AB  - The annotation of noncoding RNA genes remains a major bottleneck in genome
      sequencing projects. Most genome sequences released today still come with sets of
      tRNAs and rRNAs as the only annotated RNA elements, ignoring hundreds of other
      RNA families. We have developed a web environment that is dedicated to noncoding
      RNA (ncRNA) prediction, annotation, and analysis and allows users to run a
      variety of tools in an integrated and flexible manner. This environment offers
      complementary ncRNA gene finders and a set of tools for the comparison,
      visualization, editing, and export of ncRNA candidates. Predictions can be
      filtered according to a large set of characteristics. Based on this environment,
      we created a public website located at http://RNAspace.org. It accepts genomic
      sequences up to 5 Mb, which permits for an online annotation of a complete
      bacterial genome or a small eukaryotic chromosome. The project is hosted as a
      Source Forge project (http://rnaspace.sourceforge.net/).

PMID- 21947202
TI  - Ultra-sensitive microfibre absorption detection in a microfluidic chip.
AB  - We report a microfibre absorption sensor by using a 900 nm diameter silica
      microfibre embedded in a 125 MUm wide microchannel with a detection length of 2.5
      cm. Investigated by measuring the absorbance of methylene blue (MB), the sensor
      shows a detection limit down to 50 pM with excellent reversibility in a
      concentration range of 0-5 nM. The sensor has also been applied to bovine serum
      albumin (BSA) measurement, with a detection limit of 10 fg mL(-1). In addition,
      the sample volume requirement is merely 500 nL with a probing light power of
      about 150 nW, which is very promising for safe detection of single or a few
      molecules of biological specimens.

PMID- 21947201
TI  - A Drosophila genetic screen yields allelic series of core microRNA biogenesis
      factors and reveals post-developmental roles for microRNAs.
AB  - Canonical animal microRNAs (miRNAs) are ~22-nt regulatory RNAs generated by
      stepwise cleavage of primary hairpin transcripts by the Drosha and Dicer RNase
      III enzymes. We performed a genetic screen using an miRNA-repressed reporter in
      the Drosophila eye and recovered the first reported alleles of fly drosha, an
      allelic series of its dsRBD partner pasha, and novel alleles of dicer-1. Analysis
      of drosha mutants provided direct confirmation that mirtrons are independent of
      this nuclease, as inferred earlier from pasha knockouts. We further used these
      mutants to demonstrate in vivo cross-regulation of Drosha and Pasha in the intact
      animal, confirming remarkable conservation of a homeostatic mechanism that aligns
      their respective levels. Although the loss of core miRNA pathway components is
      universally lethal in animals, we unexpectedly recovered hypomorphic alleles that
      gave adult escapers with overtly normal development. However, the mutant
      photoreceptor neurons exhibited reduced synaptic transmission, without
      accompanying defects in neuronal development or maintenance. These findings
      indicate that synaptic function is especially sensitive to optimal miRNA pathway
      function. These allelic series of miRNA pathway mutants should find broad usage
      in studies of miRNA biogenesis and biology in the Drosophila system.

PMID- 21947203
TI  - Targeting autophagy enhances BO-1051-induced apoptosis in human malignant glioma
      cells.
AB  - PURPOSE: BO-1051 is an N-mustard derivative that is conjugated with DNA-affinic 9
      anilinoacridine. Since BO-1051 was reported to have strong anticancer activity,
      we investigated the effect and underlying mechanism of BO-1051 in human glioma
      cell lines. METHODS: Human glioma cell lines U251MG and U87MG were studied with
      BO-1051 or the combination of BO-1051 and autophagic inhibitors. Growth
      inhibition was assessed by MTT assay. Apoptosis was measured by annexin V
      staining followed by flow cytometry and immunoblotting for apoptosis-related
      molecules. Induction of autophagy was detected by acridine orange labeling,
      electron microscopy, LC3 localization and its conversion. Transfection of shRNA
      was used to determine the involvement of Beclin1 in apoptotic cell death.
      RESULTS: MTT assay showed that BO-1051 suppressed the viability of four glioma
      cell lines (U251MG, U87MG, GBM-3 and DBTRG-05MG) in a dose-dependent manner. The
      IC(50) values of BO-1051 for the glioma cells were significantly lower than the
      values for primary neurons cultures and normal fibroblast cells. Moreover, BO
      1051 not only induced apoptotic cell death, but also enhanced autophagic flux via
      inhibition of Akt/mTOR and activation of Erk1/2. Importantly, suppression of
      autophagy by 3-methyladenine or bafilomycin A1 significantly increased BO-1051
      induced apoptotic cell death in U251MG and U87MG cells. In addition, the
      proportion of apoptotic cells after BO-1051 treatment was enhanced by co
      treatment with shRNA against Beclin1. CONCLUSIONS: BO-1051 induced both apoptosis
      and autophagy, and inhibition of autophagy significantly augmented the cytotoxic
      effect of BO-1051. Thus, a combination of BO-1051 and autophagic inhibitors
      offers a potentially new therapeutic modality for the treatment of malignant
      glioma.

PMID- 21947204
TI  - Graphene as membrane for encapsulation of yeast cells: protective and
      electrically conducting.
AB  - Graphene sheets (chemically reduced), a high modulus and high thermal and
      electrically conductive material are coupled with yeast cells to form an
      encapsulating inorganic functional layer. The coupling of the high modulus sheets
      with the cells increases their stability to osmotic stresses. The sheets also
      allow the direct visualization of the cells in an electron microscope.

PMID- 21947205
TI  - Structure of collagenase G reveals a chew-and-digest mechanism of bacterial
      collagenolysis.
AB  - Collagen constitutes one-third of body protein in humans, reflecting its
      extensive role in health and disease. Of similar importance, therefore, are the
      idiosyncratic proteases that have evolved for collagen remodeling. The most
      efficient collagenases are those that enable clostridial bacteria to colonize
      their host tissues; but despite intense study, the structural and mechanistic
      basis of these enzymes has remained elusive. Here we present the crystal
      structure of collagenase G from Clostridium histolyticum at 2.55-A resolution. By
      combining the structural data with enzymatic and mutagenesis studies, we derive a
      conformational two-state model of bacterial collagenolysis, in which recognition
      and unraveling of collagen microfibrils into triple helices, as well as unwinding
      of the triple helices, are driven by collagenase opening and closing.

PMID- 21947207
TI  - Serum and lipoprotein sitostanol and non-cholesterol sterols after an acute dose
      of plant stanol ester on its long-term consumption.
AB  - PURPOSE: Chronic inhibition of cholesterol absorption with large doses of plant
      stanol esters (staest) alters profoundly cholesterol metabolism, but it is
      unknown how an acute inhibition with a large staest dose alters the postprandial
      serum and lipoprotein cholesterol precursor, plant sterol, and sitostanol
      contents. METHODS: Hypercholesterolemic subjects, randomly and double-blind
      divided into control (n = 18) and intervention groups (n = 20), consumed
      experimental diet without and with staest (plant stanols 8.8 g/day) for 10 weeks.
      Next morning after a fasting blood sample (0 h), the subjects had a breakfast
      without or with staest (4.5 g of plant stanols). Blood sampling was repeated 4 h
      later. Lipoproteins were separated with ultracentrifugation, and sterols were
      measured with gas-liquid chromatography. RESULTS: In 0-h chylomicrons and VLDL,
      plant sterols were lower in staest than in controls. Postprandially, cholestenol
      (cholesterol synthesis marker) was reduced in chylomicrons in staest compared
      with controls (-0.13 +/- 0.04 MUg/dL vs. 0.01 +/- 0.08 MUg/dL, P < 0.05). Staest
      decreased postprandially avenasterol in chylomicrons (P < 0.05 from 0 h).
      Sitostanol was high at 0 h by chronic staest in serum and VLDL but not in
      chylomicrons. Postprandial sitostanol was increased by staest in VLDL only.
      CONCLUSIONS: Chronic cholesterol absorption inhibition with large amount of plant
      stanol esters decreases plant sterols in triglyceride-rich lipoproteins. Acute
      plant stanol ester consumption increases sitostanol content in triglyceride-rich
      lipoproteins but suggests to decrease the risk of plant sterol and plant stanol
      accumulation into vascular wall by chylomicrons.

PMID- 21947206
TI  - The export factor Yra1 modulates mRNA 3' end processing.
AB  - The Saccharomyces cerevisiae mRNA export adaptor Yra1 binds the Pcf11 subunit of
      cleavage-polyadenylation factor CF1A that links export to 3' end formation. We
      found that an unexpected consequence of this interaction is that Yra1 influences
      cleavage-polyadenylation. Yra1 competes with the CF1A subunit Clp1 for binding to
      Pcf11, and excess Yra1 inhibits 3' processing in vitro. Release of Yra1 at the 3'
      ends of genes coincides with recruitment of Clp1, and depletion of Yra1 enhances
      Clp1 recruitment within some genes. These results suggest that CF1A is not
      necessarily recruited as a complete unit; instead, Clp1 can be incorporated co
      transcriptionally in a process regulated by Yra1. Yra1 depletion causes
      widespread changes in poly(A) site choice, particularly at sites where the
      efficiency element is divergently positioned. We propose that one way Yra1
      modulates cleavage-polyadenylation is by influencing co-transcriptional assembly
      of the CF1A 3' processing factor.

PMID- 21947217
TI  - Fluorescence excitation and excited state intramolecular proton transfer of jet
      cooled naphthol derivatives: part 2. 2-Hydroxy-1-naphthaldehyde.
AB  - The S(1)<- S(0) fluorescence excitation spectrum of jet-cooled 2-hydroxy-1
      naphthaldehyde (2H1N) with origin at 26,668 cm(-1) has been measured. Nine
      totally symmetric modes and three non-totally symmetric modes have been assigned
      in the excitation spectrum. Ab initio calculations indicate that 2H1N undergoes a
      planarity change upon excitation, which may account for the unusual intensity of
      non totally symmetric vibrational modes in the excitation spectrum. A number of
      low intensity features were observed on the low energy side of the origin which
      have been assigned to the 2H1N dimer rather than different ground state confomers
      of 2H1N. The origin of the S(1)<- S(0) electronic transition of the dimer lies at
      ~26,401 cm(-1); combinations of two low frequency intermolecular modes of the
      dimer (59 cm(-1) and 17 cm(-1)) were also observed. The occurrence of excited
      state intramolecular proton transfer (ESIPT) in 2H1N cannot be proven on the
      basis of this work. A comparison of the (photo)physical properties of 2H1N with 1
      hydroxy-2-naphthaldehyde (1H2N) [A. McCarthy and A.A. Ruth, PCCP, 2011, 13, 7485
      7499 (Part 1)], however, indicate the plausibility of an ESIPT process in 2H1N.
      The strength of the intramolecular hydrogen bond (IMHB) in 2H1N was computed as
      ~10.6 kcal/mol, a value comparable to the IMHB strength of 1H2N. The
      establishment of a lower limit on the state lifetimes of 2H1N, of ~1.8 ps,
      indicates that any proposed ESIPT reaction in 2H1N may not proceed barrierlessly.
      Above an excess energy of ~1000 cm(-1), the intensity of the fluorescence
      excitation spectrum reduces significantly, indicating the onset of a non
      radiative decay mechanism.

PMID- 21947219
TI  - Lane-Hamilton syndrome: case report and review of the literature.
AB  - We report a case of a three-and-a-half-year-old boy, who presented with poor
      general condition, stunted growth, had the presence of nail clubbing, persistent
      cough and frequent diarrhoea. Persistent iron deficiency anaemia without signs of
      haemolysis suggested Lane-Hamilton syndrome (LHS) which is or/is an extremely
      rare combination of idiopathic pulmonary haemosiderosis (IPH) and celiac disease
      (CD), although both diseases are immunologically mediated and the pathogenetic
      link between them is not clear. We have now 3 years of follow-up on gluten-free
      diet (GFD), resulting in a gradual recovery of the abnormal laboratory results in
      combination with an improving growth. Clinically, he is asymptomatic without any
      additional treatment. Our case illustrates that CD should be specifically looked
      for in patients with IPH, especially those in whom the severity of anaemia is
      disproportionate to the IPH symptoms. Both diseases may benefit from a GFD.

PMID- 21947218
TI  - [The development of depression: the role of brain-derived neurotrophic factor].
AB  - An association between the presence of psychosocial stress, its pathological
      processing and the development of depression is well documented. This review
      reports and discusses studies suggesting a reduced release of brain-derived
      neurotrophic factor (BDNF) under stress as a possible mechanism. The studies show
      a reduction of BDNF secretion in stressful situations, a decreased blood
      concentration in depression and a normalization of BDNF by successful
      antidepressant therapy. As a possible mechanism of BDNF action, a reactivation of
      neuroplasticity is being discussed, especially in hippocampal and cortical
      networks. On the other hand, methodological limitations, such as the
      impossibility of determining the cerebral BDNF concentration in vivo and ruling
      out a variety of possible confounders, may restrict the significance of the
      studies. The question of whether the ascertained changes of BDNF levels are
      causally involved in the pathophysiology of depression or whether they are just
      an epiphenomenal result of depression-induced stress is still under debate.

PMID- 21947220
TI  - Vitamin B12 deficiency in a 9-month-old boy.
AB  - We present a 9-month-old boy with megaloblastic anaemia, neutropenia and
      hypogammaglobulinaemia due to vitamin B12 deficiency. The deficiency was
      secondary to prolonged exclusive breastfeeding with inadequate nutritional
      amounts of vitamin B12 from the mother. There were no clinical or biological
      signs of maternal anaemia or macrocytosis. Treatment with oral vitamin B12
      rapidly improved the biological findings of the child. Vitamin B12 deficiency
      should be considered in infants older than 2 months presenting with failure to
      thrive, neurocognitive retardation or even pancytopenia and
      hypogammaglobulinaemia, even in the absence of any signs of maternal anaemia or
      macrocytosis. Therefore, evaluation of vitamin B12 status during pregnancy and
      lactation is necessary in order to prevent B12 deficiency and its possible long
      term effects in infants. CONCLUSION: Further studies should be conducted to
      evaluate the optimal oral dosage of vitamin B12 in children since limited data on
      the use of oral B12 substitution are available.

PMID- 21947221
TI  - Gynaecological and obstetric bleeding in moderate and severe von Willebrand
      disease.
AB  - A nation-wide cross-sectional study was initiated to assess gynaecological and
      obstetrical symptoms in an unselected cohort of women with moderate and severe
      von Willebrand disease (VWD) in the Netherlands. A total of 423 women aged >=16
      years were included. Bleeding severity was measured using the Tosetto Bleeding
      Score (BS). Menorrhagia, defined as occurrence of >=2 menorrhagia symptoms, was
      reported by 81%. Of all VWD women, 78% received any kind of treatment for
      menorrhagia and 20% underwent a hysterectomy predominantly because of severe
      menstrual bleeding. Over half of the women reported more blood loss than can be
      expected with a normal delivery. In 52% of reported pregnancy losses curettage
      was needed because of bleeding. Mean number of live births was 1.9, which is
      comparable with the general Dutch population. In conclusion, women with moderate
      or severe VWD frequently have menorrhagia in need of treatment, and 20% of the
      VWD women underwent a hysterectomy. Bleeding complications occurred in over 50%
      of the women after childbirth or pregnancy loss. Progeny seems not to be affected
      in women with moderate or severe VWD.

PMID- 21947222
TI  - Wildervanck's syndrome and mirror movements: a congenital disorder of axon
      migration?
AB  - Cell outgrowth and migration in the developing nervous system result from
      guidance cues, whose molecular bases and clinical correlates are only partly
      known. We describe a patient with brain stem malformation, paroxysmal left sided
      lacrimation when eating ("crocodile tears") and mirror movements in addition to
      Wildervanck's cervico-oculo-acusticus (COA) syndrome, which encompasses Klippel
      Feil anomaly, congenital hearing loss and Duane's syndrome. The unique symptom
      constellation has not been reported in that combination before and can be
      discussed in the context of congenital disordered axonal migration based on
      dysfunction of signalling pathways. However, mutations in some recently
      discovered genes, associated with single findings also present in our patient,
      were not found. Therefore, we suppose that the disturbance of an as yet unknown
      regulatory factor may explain the congenital malformation syndrome of our
      patient. In general, only a few human disorders have yet been found to result
      from defects in axon guidance. Nevertheless, disorders of axon guidance can
      certainly be regarded as a new category of neurodevelopmental disorders.

PMID- 21947223
TI  - A Multidimensional Prognostic Index (MPI) based on a comprehensive geriatric
      assessment predicts short- and long-term all-cause mortality in older
      hospitalized patients with transient ischemic attack.
AB  - A multidimensional impairment may influence the clinical outcome of acute
      diseases in older patients. The aim of the current study was to evaluate whether
      a Multidimensional Prognostic Index (MPI) based on a comprehensive geriatric
      assessment (CGA) predicts short- and long-term all-cause mortality in older
      patients hospitalized for transient ischemic attack (TIA). In this prospective
      study with 1-year follow-up, 654 patients aged 65 and older with a diagnosis of
      TIA according to the International Classification of Diseases, Ninth Revision,
      Clinical Modification (ICD-9-CM 435.x) were enrolled. A standardized CGA that
      included information on functional (activities of daily living, ADL, and
      Instrumental ADL), cognitive status (Short Portable Mental Status Questionnaire),
      nutrition (Mini Nutritional Assessment), risk of pressure sores (Exton-Smith
      Scale), comorbidities (Cumulative Illness Rating Scale), medications and co
      habitation status was used to calculate the MPI for mortality using a previously
      validated algorithm. Higher MPI values were significantly associated with higher
      1-month all-cause mortality (incidence rates: MPI-1 low risk = 0.32%, MPI-2
      moderate risk = 5.36%, MPI-3 high risk = 10.42%; p < 0.001), 6-month all-cause
      mortality (MPI-1 = 1.95%, MPI-2 = 9.77%, MPI-3 = 27.22%; p < 0.001) and 12-month
      all-cause mortality (MPI-1 = 5.19%, MPI-2 = 16.47%, MPI-3 = 44.32%; p < 0.001).
      Age- and gender-adjusted Cox regression analyses demonstrated that MPI was a
      significant predictor of all-cause mortality. MPI showed a significant high
      discriminatory power with an area under the receiver operating characteristics
      (ROC) curve of 0.819, 95% CI = 0.749-0.888 for 1-month mortality, 0.799, 95% CI =
      0.738-0.861 for 6-month mortality and 0.770, 95% CI = 0.716-0.824 for 12-month
      mortality. The MPI, calculated from information collected in a standardized CGA,
      appeared to be effective in estimating short- and long-term all-cause mortality
      in older patients hospitalized for TIA.

PMID- 21947224
TI  - Migration and multiple sclerosis in United Kingdom and Ireland immigrants to
      Australia: a reassessment. II. Characteristics of early (pre-1947) compared to
      later migrants.
AB  - In our recent reassessment we explored the risk of MS by age at immigration in
      258 migrants from United Kingdom and Ireland (UKI) to four states of Australia
      (New South Wales, Queensland, South Australia, and Western Australia) in the
      period 1947-1981 (Group II). In the present report we have compared their
      characteristics with 44 cases who migrated before 1947 (Group I), divided into
      two subsets: Group Ia (15 cases) was rather similar to Group II in age at
      immigration (means of 20 and 23 years), age at onset (39 and 33 years), and
      duration from immigration to onset (19 and 10 years). Group Ib (29 cases) was
      significantly different from Group II, with mean ages of 4 years at immigration
      and 40 years at onset, for a mean interval of some 35 years between immigration
      and onset. All onsets in Group Ib occurred after 1947. We concluded that the
      Group Ib cases had most probably acquired their MS in Australia. Immigrants from
      high MS risk countries, including UKI, were modest in number before 1947, but
      some 770,000 entered from 1947-1981. They may have been the source of MS for the
      Group Ib migrants.

PMID- 21947225
TI  - The Munich Diagnostic and Predictor Study of Dizziness: objectives, design, and
      methods.
AB  - This report describes the objectives, design, and methods of the Munich
      Diagnostic and Predictor Study of Dizziness, a prospective study investigating
      diagnostic subgroups, correlates, and predictors of dizziness that is not
      sufficiently explained medically but clearly related to a psychiatric disorder.
      All patients presenting at the Integrated Centre for Research and Treatment of
      Vertigo, Balance and Ocular Motor Disorders at the University Hospital
      Grobetahadern in Munich, Germany, are investigated during their first-time visit.
      The study consists of a baseline and two follow-up assessment points at 6 and 12
      months. At the baseline assessment point, all participants complete self-rated
      questionnaires concerning dizziness, depression, anxiety, dissociative and
      traumatic experiences, somatization, body sensations and perception, cognitions,
      attachment, personality, quality of life and experiences with the health care
      system. Additionally, a structured clinical interview is conducted to assess
      mental disorders. Then, the neurologists complete questionnaires regarding the
      subjective doctor-patient relationship and to document the somatic diagnoses and
      results. The follow-up measurements consist of self-rated questionnaires. This
      study aims to improve the diagnosis and treatment of patients who suffer from
      dizziness related to a psychiatric disorder and who are often severely impaired
      in their working and daily lives.

PMID- 21947226
TI  - Passive droplet trafficking at microfluidic junctions under geometric and flow
      asymmetries.
AB  - When droplets enter a junction they sort to the channel with the highest flow
      rate at that instant. Transport is regulated by a discrete time-delayed feedback
      that results in a highly periodic behavior where specific patterns can continue
      to cycle indefinitely. Between these highly ordered regimes are chaotic
      structures where no pattern is evident. Here we develop a model that describes
      droplet sorting under various asymmetries: branch geometry (length, cross
      section), droplet resistance and pressures. First, a model is developed based on
      the continuum assumption and then, with the assistance of numerical simulations,
      a discrete model is derived to predict the length and composition of the sorting
      pattern. Furthermore we derive all unique sequences that are possible for a given
      distribution and develop a preliminary estimation of why chaotic regimes form.
      The model is validated by comparing it to numerical simulations and results from
      microfluidic experiments in PDMS chips with good agreement.

PMID- 21947227
TI  - Decrease of guanylyl cyclase beta1 subunit and nitric oxide (NO)-induced
      relaxation in mouse rectum with colitis and its reproduction on long-term NO
      treatment.
AB  - Nitric oxide (NO) influences motility in the colon in patients with ulcerative
      colitis, but the exact mechanism involved remains unknown. Colitis was induced in
      mice by the oral administration of 2.5% dextran sodium sulfate (DSS), and the
      motility in longitudinal preparations from rectum and distal colon and expression
      of beta1 subunit of soluble guanylyl cyclase (sGCbeta1) were analyzed. Electrical
      stimulation (ES) caused a transient relaxation via the NO pathway in both rectum
      and colon from control mice. Stimulation with sodium nitroprusside (SNP) caused
      relaxation in the two regions, and the half-time (T (1/2)) of the maximal
      relaxation induced by 100 MUM SNP was 8.1 +/- 1.0 s in rectum. DSS treatment (1)
      abolished the ES-induced relaxation, but not dibutyryl cyclic GMP-induced
      response, in both regions, (2) decreased the maximal response to SNP accompanied
      by a loss of immunoreactive sGCbeta1 protein in rectum, but did not affect the
      amplitude of the relaxant response or the protein in distal colon, and (3) caused
      an increase in the T (1/2) value in response to SNP in both regions. Pretreatment
      of both preparations from control mice with 600 MUM SNP for 30 min decreased both
      ES- and SNP-induced relaxation, SNP-induced cyclic GMP formation, and
      immunoreactive sGCbeta1 levels. NO-mediated relaxation was impaired by a
      dysfunctional sGC with and without a loss of immunoreactivity to sGCbeta1 in
      rectum and colon from DSS-treated mice, respectively. Long-term exposure of the
      tissues with an excess amount of NO changes the sGC-mediated relaxation.

PMID- 21947228
TI  - Chitooligosaccharides attenuate UVB-induced damages in human dermal fibroblasts.
AB  - As a continuation of our research on chitooligosaccharides (COS), this study
      focused on the protective effect of COS of various molecular weights (1-3, 3-5,
      and 5-10 kDa) on cellular damage caused by ultraviolet B (UVB)-induced oxidative
      stress in human dermal fibroblast cells. The results show that the protective
      effect of COS on UVB-stressed human fibroblasts was dependent on molecular
      weight. COS suppressed UVB irradiation-induced reactive oxygen species generation
      and DNA damage, accompanied by the downregulation of matrix metalloproteinase
      (MMP)-1 and MMP-13. In a comparative analysis, COS (3-5 kDa) exhibited the most
      potent protective effect on UVB-stressed fibroblasts. The presence of COS (3-5
      kDa) attenuated UVB-induced collagenolytic MMP production and collagen
      degradation. The photoprotective activity of COS (3-5 kDa) was confirmed by
      transcriptional phosphorylation of mitogen-activated protein kinase-responsive
      signaling pathways.

PMID- 21947229
TI  - Protective effect of andrographolide against concanavalin A-induced liver injury.
AB  - This study was designed to investigate the hepatic protective effect and the
      molecular mechanisms of andrographolide in concanavalin A-induced liver injury
      model. Results showed that andrographolide (Ag) attenuated concanavalin A (Con-A)
      induced liver injury and inhibited hepatocyte apoptosis. Further results showed
      that oxidative stress response genes were significantly elevated during the
      pathogenesis induced by Con-A. Meanwhile, gadolinium chloride and N-acetyl-L
      cysteine (NAC) treatment, which inactivates Kupffer cells or reduces reactive
      oxygen species, respectively, prevented the liver injury. So the messenger RNA
      levels of the oxidative response genes mentioned above were detected, and the
      following results showed that Ag treatment reduced their expression. Besides,
      serum lactate dehydrogenase and myeloperoxidase activity was significantly
      reduced by Ag. Finally, Ag treatment did not further reduce serum tumor necrosis
      factor-alpha production compared with NAC treatment alone. Thus, our results
      indicate that Ag prevents Con-A-induced liver injury and reduced the hepatic
      oxidative stress response. The hepatic protective effect of Ag indicates that Ag
      supplementation may be beneficial in the treatment of immune-mediated liver
      injury.

PMID- 21947230
TI  - Inhibition of the adenylyl cyclase toxin, edema factor, from Bacillus anthracis
      by a series of 18 mono- and bis-(M)ANT-substituted nucleoside 5'-triphosphates.
AB  - Bacillus anthracis causes anthrax disease and exerts its deleterious effects by
      the release of three exotoxins, i.e. lethal factor, protective antigen and edema
      factor (EF), a highly active calmodulin-dependent adenylyl cyclase (AC).
      Conventional antibiotic treatment is ineffective against either toxaemia or
      antibiotic-resistant strains. Thus, more effective drugs for anthrax treatment
      are needed. Our previous studies showed that EF is differentially inhibited by
      various purine and pyrimidine nucleotides modified with N-methylanthraniloyl
      (MANT)- or anthraniloyl (ANT) groups at the 2'(3')-O-ribosyl position, with the
      unique preference for the base cytosine (Taha et al., Mol Pharmacol 75:693
      (2009)). MANT-CTP was the most potent EF inhibitor (K (i), 100 nM) among 16
      compounds studied. Here, we examined the interaction of EF with a series of 18
      2',3'-O-mono- and bis-(M)ANT-substituted nucleotides, recently shown to be very
      potent inhibitors of the AC toxin from Bordetella pertussis, CyaA (Geduhn et al.,
      J Pharmacol Exp Ther 336:104 (2011)). We analysed purified EF and EF mutants in
      radiometric AC assays and in fluorescence spectroscopy studies and conducted
      molecular modelling studies. Bis-MANT nucleotides inhibited EF competitively.
      Propyl-ANT-ATP was the most potent EF inhibitor (K (i), 80 nM). In contrast to
      the observations made for CyaA, introduction of a second (M)ANT-group decreased
      rather than increased inhibitor potency at EF. Activation of EF by calmodulin
      resulted in effective fluorescence resonance energy transfer (FRET) from
      tryptophan and tyrosine residues located in the vicinity of the catalytic site to
      bis-MANT-ATP, but FRET to bis-MANT-CTP was only small. Mutations N583Q, K353A and
      K353R differentially altered the inhibitory potencies of bis-MANT-ATP and bis
      MANT-CTP. The nucleotide binding site of EF accommodates bulky bis-(M)ANT
      substituted purine and pyrimidine nucleotides, but the fit is suboptimal compared
      to CyaA. These data provide a basis for future studies aiming at the development
      of potent EF inhibitors with high selectivity relative to mammalian ACs.

PMID- 21947231
TI  - Muscarinic receptor subtypes and signalling involved in the attenuation of
      isoprenaline-induced rat urinary bladder relaxation.
AB  - beta-Adrenoceptors are important mediators of smooth muscle relaxation in the
      urinary bladder, but the concomitant presence of a muscarinic agonist, e.g.,
      carbachol, can attenuate relaxation responses by reducing potency and/or efficacy
      of beta-adrenoceptor agonists such as isoprenaline. Therefore, the present study
      was designed to explore the subtypes and signalling pathways of muscarinic
      receptors involved in the attenuation of isoprenaline-induced isolated rat
      detrusor preparations using novel subtype-selective receptor ligands. In
      radioligand binding studies, we characterized BZI to be a M(3)-sparing muscarinic
      agonist, providing selective M(2) stimulation in rat bladder, and THRX-182087 as
      a highly M(2)-selective antagonist. The use of BZI and of THRX-182087 in the
      presence of carbachol enabled experimental conditions with a selective
      stimulation of only M(2) or M(3) receptors, respectively. Confirming previous
      findings, carbachol attenuated isoprenaline-induced detrusor relaxation. M(2)
      selective stimulation partly mimicked this attenuation, indicating that both M(2)
      and M(3) receptors are involved. During M(3)-selective stimulation, the
      attenuation of isoprenaline responses was reduced by the phospholipase C
      inhibitor U 73,122 but not by the protein kinase C inhibitor chelerythrine. We
      conclude that both M(2) and M(3) receptors contribute to attenuation of beta
      adrenoceptor-mediated relaxation of rat urinary bladder; the signal transduction
      pathway involved in the M(3) component of this attenuation differs from that
      mediating direct contractile effects of M(3) receptors.

PMID- 21947232
TI  - Remarkable extension of PAI-1 half-life surprisingly brings no changes to its
      structure.
AB  - Plasminogen activator inhibitor type 1 (PAI-1) is a serpin protein, a natural
      inhibitor of urokinase (uPA) and tissue plasminogen activators (tPA). By
      inhibiting uPA it can block growth of the cancer tumors by suppressing
      angiogenesis, while when acting on tPA in the blood it can avert conversion of
      plasminogen to plasmin preventing lysis of the clot. Furthermore, blocking PAI-1
      activity can protect against thrombosis. Thus PAI-1 makes great impact on human
      homeostasis and is desirable for clinical application. Wild-type PAI-1 (wt-PAI-1)
      has a short span of activity with a t1/2 of ~2 h, being spontaneously converted
      into a latent form. An enormous effort has been made to create a more stable
      molecule with >600 PAI-1 variants constructed to study its structure-function
      relationship. In the present study, we evaluate the structure of the active
      recombinant VLHL-PAI-1 (very long half life, active >700 h) which is glycosylated
      similarly to wt-PAI-1 at N232 and N288, with the extended reactive center loop,
      intact engineered -S-S-bridge (Q174C, G323C) that precludes latency without
      affecting structure, and can be controlled by a reducing agent to terminate
      activity at will. We have already proven its usefulness to control cancer in
      human cancer cells, as well as preventing clot lysis in human whole blood and
      plasma and in a mouse model. Our results demonstrate the potential therapeutic
      applications (topical or systemic) of this protein in the treatment of cancer,
      for the trauma patients to ward off an excessive blood loss, or for people with
      the PAI-1 deficiency, especially during surgery.

PMID- 21947233
TI  - Vitamin D receptor gene polymorphism in children with urinary tract infection.
AB  - It is known that small alterations leading to different vitamin D receptor (VDR)
      alleles affect resistance or susceptibility to infections. In this study, we
      examined VDR gene polymorphisms in urinary tract infections (UTI), which are
      common and an important cause of morbidity in children and subsequently of renal
      scar formation. We evaluated 92 patients diagnosed with UTI and 105 children
      without prior history of UTI as a control group. The VDR gene polymorphisms BsmI,
      FokI, ApaI, and TaqI were evaluated in patients and controls. BsmI polymorphism
      genotype distribution was similar between groups. There was a significant
      difference between groups for FokI (p =0 < 001); for the ff genotype, the risk of
      UTI was significantly increased (p < 0.01) ,at 3.94 times higher (odds ratio =
      3.94; 95% confidence interval 1.71-9.09). ApaI polymorphism was significantly
      increased in the control group (p < 0.01) and evaluated as a protective factor.
      Comparing the TaqI genotype between groups, there was no statistically
      significant difference, but in both Tt and tt genotypes, there was minimal
      increased risk of UTI. The results of this study suggest that VDR gene
      polymorphisms can be important for susceptibility to UTI and renal scar
      formation. Association between VDR polymorphisms and UTI is in accordance with
      the understanding of how vitamin D modulates the immune response against
      infections.

PMID- 21947234
TI  - Characterizing cytochrome c states--TERS studies of whole mitochondria.
AB  - Protein structures (cytochrome c) were visualized by TERS measurements on whole
      mitochondria referring to specific spectral features describing the electronic
      state of the heme moiety.

PMID- 21947235
TI  - Intramesosigmoid hernia: preoperative diagnostic MDCT findings.
AB  - Internal hernias, protrusion of abdominal viscera into an intraperitoneal fossa,
      are uncommon causes of bowel obstruction, and preoperative diagnoses are
      difficult. We report a rare case of a 47-year-old female with strangulated small
      bowel obstruction secondary to an intramesosigmoid hernia preoperative diagnosis
      by multi-detector row computed tomography. We highlight the preoperatively
      diagnosed value and findings of MDCT in intramesosigmoid hernia.

PMID- 21947236
TI  - Acid-base thermochemistry of gaseous oxygen and sulfur substituted amino acids
      (Ser, Thr, Cys, Met).
AB  - Acid-base thermochemistry of isolated amino acids containing oxygen or sulfur in
      their side chain (serine, threonine, cysteine and methionine) have been examined
      by quantum chemical computations. Density functional theory (DFT) was used, with
      B3LYP, B97-D and M06-2X functionals using the 6-31+G(d,p) basis set for geometry
      optimizations and the larger 6-311++G(3df,2p) basis set for energy computations.
      Composite methods CBS-QB3, G3B3, G4MP2 and G4 were applied to large sets of
      neutral, protonated and deprotonated conformers. Conformational analysis of these
      species, based on chemical approach and AMOEBA force field calculations, has been
      used to identify the lowest energy conformers and to estimate the population of
      conformers expected to be present at thermal equilibrium at 298 K. It is observed
      that G4, G4MP2, G3B3, CBS-QB3 composite methods and M06-2X DFT lead to similar
      conformer energies. Thermochemical parameters have been computed using either the
      most stable conformers or equilibrium populations of conformers. Comparison of
      experimental and theoretical proton affinities and Delta(acid)H shows that the G4
      method provides the better agreement with deviations of less than 1.5 kJ mol(-1).
      From this point of view, a set of evaluated thermochemical quantities for serine,
      threonine, cysteine and methionine may be proposed: PA = 912, 919, 903, 938; GB =
      878, 886, 870, 899; Delta(acid)H = 1393, 1391, 1396, 1411; Delta(acid)G = 1363,
      1362, 1367, 1382 kJ mol(-1). This study also confirms that a non-negligible
      DeltapS degrees  is associated with protonation of methionine and that the most
      acidic hydrogen of cysteine in the gas phase is that of the SH group. In several
      instances new conformers were identified thus suggesting a re-examination of
      several IRMPD spectra.

PMID- 21947237
TI  - LysGH15B, the SH3b domain of staphylococcal phage endolysin LysGH15, retains high
      affinity to staphylococci.
AB  - LysGH15, a phage endolysin, exhibits a particularly broad lytic spectrum against
      Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA).
      Sequence analysis reveals that this endolysin contains a C-terminal cell wall
      binding domain (SH3b), which causes the endolysin to bind to host strains. In
      this study, the substrate binding affinity of the SH3b domain (LysGH15B) was
      evaluated. A fusion protein of LysGH15B and green fluorescent protein (LysGH15B
      GFP) were cloned and expressed in Escherichia coli. Laser scanning confocal
      microscopy was used to detect the fluorescence of the treated cells irradiated at
      different excitation wavelengths and to determine the binding activity of
      LysGH15B-GFP and GFP. We found that LysGH15B-GFP not only generated green
      fluorescence, but, more importantly, also displayed specific affinity to
      staphylococcal isolates, especially MRSA. In contrast, the single GFP did not
      display any binding activity. The high affinity was attributed to the portion of
      LysGH15B and the binding activity of the fusion protein was specific to
      staphylococci. This study provides an insight into the SH3b domain of LysGH15.
      The specific binding activity may cause LysGH15B to serve as an anchoring device,
      and offer an alternative approach for cell surface attachment onto staphylococci.

PMID- 21947238
TI  - [Quality management and certification - what for?].

PMID- 21947239
TI  - [Certification of breast centers].
AB  - The primary focus of the establishment and certification of specialized cancer
      centers in the context of the National Cancer Plan is to improve the quality of
      care for patients with various carcinoma entities. The era of organ center
      certification started with the establishment of specialized breast cancer centers
      in line with the high incidence of breast cancer, the high mortality rate and the
      high level of interdisciplinary cooperation in the diagnosis and therapy of
      breast cancer. The introduction of quality management and external monitoring
      aims to provide high quality care in the diagnosis and therapy of breast cancer
      and is expected to improve long-term quality data (disease-free survival and
      overall survival) and to reduce mortality rates by about 25-30%. Certification
      requires the implementation of a quality management system and care provision
      structures assuring diagnosis and therapy according to the quality guidelines and
      recommendations of the specialist societies. Basic requirements for improving the
      quality of breast cancer patient care are centralization, specialization and
      interdisciplinarity. It has been demonstrated that the improvement of overall
      survival is associated with an increasing annual case load of a center, an
      increasing case load per surgeon per year, study participation and
      interdisciplinarity. Tumor documentation will be harmonized in the future by the
      establishment of local clinical cancer registries and cross-linking them with the
      National Cancer Registry. The data collection and analysis of several quality
      markers and current follow-up and survival data for each breast cancer patient
      will allow direct comparison of participating institutions. Individual breast
      cancer centers may demonstrate quality improvement longitudinally. Both
      certification and specialization require additional services which are associated
      with a substantial increase in costs. Preliminary data suggest that certified
      breast cancer centers are dependent on cross-financing by the participating
      departments of a hospital. Up to now cost-effective analyses for certified breast
      cancer centers are not available due to a substantial lack of data defining the
      additional financial burden.

PMID- 21947240
TI  - [Nephrogenic systemic fibrosis (NSF): Effects of stricter guidelines on the use
      of contrast media containing gadolinium].

PMID- 21947241
TI  - Interactions between residues 2228-2240 within factor VIIIa C2 domain and factor
      IXa Gla domain contribute to propagation of clot formation.
AB  - Factor (F)VIII functions as a cofactor in the tenase complex responsible for
      phospholipid (PL)-dependent FXa generation by FIXa. We have recently reported
      that the FVIIIa C2 domain (residues 2228-2240) interacts with the FIXa Gla domain
      in this complex. We examined the role of this interaction in the generation of
      tenase activity during the process of clot formation, using a synthetic peptide
      corresponding to residues 2228-2240. The peptide 2228-2240 inhibited FVIIIa/FIXa
      mediated FX activation dose-dependently in the presence of PL by >95% (IC50; ~10
      MUM). This effect was significantly greater than that obtained by peptide 1804
      1818 (IC50; ~180 MUM) which corresponds to another FIXa-interactive site in the
      light chain that provides the majority of binding energy for FIXa interaction.
      Peptide 2228-2240 had little effect on the prothrombin time and did not inhibit
      FIX activation in the coagulation process mediated by FVIIa/tissue factor or
      FXIa, suggesting specific inhibition of the intrinsic tenase complex. Clot
      waveform analysis, a plasma based-assay used to evaluate the process of intrinsic
      coagulation, demonstrated that peptide 2228-2240 significantly depressed both
      maximum coagulation velocity (|min1|) and acceleration (|min2|), reflecting the
      propagation of clot formation, although the clotting time was only marginally
      prolonged. Thromboelastography, an alternative whole blood based-assay,
      demonstrated that the peptide inhibited clot formation time, alpha-angle and
      maximal clot firmness, but had little effect on the clotting time. Interactions
      of the FVIIIa C2 domain (residues 2228-2240) with the FIXa Gla domain in the
      tenase complex appeared to contribute essentially to the propagation of clot
      formation.

PMID- 21947242
TI  - Calcium-binding protein S100P and cancer: mechanisms and clinical relevance.
AB  - S100P is a 95-amino-acid protein and a member of the S100 family. It was first
      purified from placenta. The promoter area of S100P has binding sites for SMAD,
      STAT/CREB and SP/KLF, key regulatory elements participating in transcriptional
      activation of the S100P gene. Increased levels of S100P have been observed in
      multiple tumor cell lines and breast, pancreas, lung and ovary carcinomas. S100P
      has been shown to mediate tumor growth, metastasis and invasion through the
      binding of Ca(2+) ions, receptor for advanced glycation end products,
      cytoskeletal protein ezrin, calcyclin-binding protein/Siah-1-interacting protein
      and cathepsin D. S100P could potentially serve as diagnostic marker,
      prognostic/predictive indicator and therapy target for different carcinomas.

PMID- 21947244
TI  - Occurrence and impact of delayed cerebral ischemia after coiling and after
      clipping in the International Subarachnoid Aneurysm Trial (ISAT).
AB  - Delayed cerebral ischemia (DCI) is an important cause of poor outcome after
      aneurysmal subarachnoid hemorrhage (SAH). We studied differences in incidence and
      impact of DCI as defined clinically after coiling and after clipping in the
      International Subarachnoid Aneurysm Trial. We calculated odds ratios (OR) for DCI
      for clipping versus coiling with logistic regression analysis. With coiled
      patients without DCI as the reference group, we calculated ORs for poor outcome
      at 2 months and 1 year for coiled patients with DCI and for clipped patients
      without, and with DCI. With these ORs, we calculated relative excess risk due to
      Interaction (RERI). Clipping increased the risk of DCI compared to coiling in the
      2,143 patients OR 1.24, 95% confidence interval (95% CI 1.01-1.51). Coiled
      patients with DCI, clipped patients without DCI, and clipped patients with DCI
      all had higher risks of poor outcome than coiled patients without DCI. Clipping
      and DCI showed no interaction for poor outcome at 2 months: RERI 0.12 (95% CI 
      1.16 to 1.40) or 1 year: RERI -0.48 (95% CI -1.69 to 0.74). Only for patients
      treated within 4 days, coiling and DCI was associated with a poorer outcome at 1
      year than clipping and DCI (RERI -2.02, 95% CI -3.97 to -0.08). DCI was more
      common after clipping than after coiling in SAH patients in ISAT. Impact of DCI
      on poor outcome did not differ between clipped and coiled patients, except for
      patients treated within 4 days, in whom DCI resulted more often in poor outcome
      after coiling than after clipping.

PMID- 21947243
TI  - Receptor for advanced glycation end products (RAGE) partially mediates HMGB1-ERKs
      activation in clear cell renal cell carcinoma.
AB  - PURPOSE: To explore the expression of receptor for advanced glycation end
      products (RAGE) and high-mobility group box-1 (HMGB1) and their role in clear
      cell renal cell carcinoma (CCRCC) development and progression. METHODS:
      Expression of RAGE and HMGB1 was examined in RCC using tissue microarrays. In
      vitro, quiescent or RAGE-reduced RCC cells were subjected to treatment with HMGB1
      and harvested for detecting ERK1/2 phosphorylation via Western blot. Further cell
      proliferation, migration and invasion were evaluated by Ki-67 immunostaining,
      wound healing and matrigel invasion assay, respectively. RESULTS: 1Elevated co
      expression of RAGE and HMGB1 in CCRCC was correlated positively with patients'
      clinical parameters including tumor size, nuclear Fuhrman grade and clinical
      stage. 2HMGB1 incubation induced ERK1/2 activation in a time- and dose-dependent
      manner, which could be completely blocked by U0126 (MEK1/2 inhibitor) and
      partially reversed by RAGE knockdown. 3RAGE knockdown partially reversed the
      promoted effect of cell proliferation, migration and invasion induced by HMGB1.
      CONCLUSION: HMGB1 promotes the development and progression of CCRCC via ERK1/2
      activation, which is partially mediated by RAGE.

PMID- 21947245
TI  - William Henry Battle (1855-1936).

PMID- 21947246
TI  - The role of protein disorder in the 14-3-3 interaction network.
AB  - Disordered regions are segments of a protein that do not fold completely and thus
      remain flexible. These regions have key physiological roles, particularly in
      phospho-proteins, which are enriched in disorder-promoting residues surrounding
      their phosphorylation sites. 14-3-3 proteins are ordered hubs that interact with
      multiple and diverse intrinsically disordered phosphorylated targets. This
      provides 14-3-3 with the ability to participate in and to regulate multiple
      signalling networks. Here, I review the effect of structural disorder on the
      mechanism involved in 14-3-3 protein-protein interactions and how 14-3-3 impacts
      cell biology through disordered ligands. How 14-3-3 proteins constitute an
      advantageous system to identify novel classes of biological tools is discussed
      with a special emphasis on a particular-and innovative-use of small molecules to
      stabilize 14-3-3 protein complexes, useful to study gene expression, cancer
      signalling and neurodegenerative diseases.

PMID- 21947247
TI  - c-Myc down-regulation is involved in proteasome inhibitor-mediated enhancement of
      radiotherapeutic efficacy in non-small cell lung cancer.
AB  - In this study, the effect of MG132 (carbobenzoxyl-leucinyl-leucinyl-leucinal-H)
      at a low dose on radiotherapeutic efficacy and its accurate mechanism of
      radiosensitization were investigated in human non-small cell lung cancer. The
      effect of MG132 on ionizing radiation (IR)-induced cytotoxicity, cell
      proliferation and survival of A549 cells was evaluated. The protein expression
      modulated by MG132 and IR were inspected by Western blot analysis. To determine
      in vivo radiotherapeutic efficacy, tumor growth delay was analyzed in a A549
      tumor-bearing xenograft mouse model after single or repeated treatment of MG132
      and/or IR. Induction of apoptosis and change of c-Myc expression in the tumor
      tissue was explored by histological analysis. MG132 at a non-toxic dose enhanced
      the radiation-induced cytotoxicity of A549 cells, accompanying a significant
      decrease of c-Myc expression. Suppression of c-Myc expression by small
      interfering RNA (siRNA) displayed enhancement of radiosensitivity similarly to
      MG132 treatment. Tumor growth in the xenograft mice was markedly delayed by
      systemic administration of MG132 combined with IR. In vivo down-regulation of c
      Myc and increased induction of apoptosis were simultaneously observed in the
      tumor tissues followed by combinational treatment of MG132 and IR. The results
      reveal a novel mechanism for proteasome inhibitor-mediated radiosensitization in
      which c-Myc down-regulation is involved.

PMID- 21947248
TI  - Radiation dose optimization in pediatric temporal bone computed tomography:
      influence of tube tension on image contrast and image quality.
AB  - INTRODUCTION: The purpose of this experimental study was to investigate the
      effect of tube tension reduction on image contrast and image quality in pediatric
      temporal bone computed tomography (CT). METHODS: Seven lamb heads with infant
      equivalent sizes were scanned repeatedly, using four tube tensions from 140 to 80
      kV while the CT-Dose Index (CTDI) was held constant. Scanning was repeated with
      four CTDI values from 30 to 3 mGy. Image contrast was calculated for the middle
      ear as the Hounsfield unit (HU) difference between bone and air and for the inner
      ear as the HU difference between bone and fluid. The influence of tube tension on
      high-contrast detail delineation was evaluated using a phantom. The subjective
      image quality of eight middle and inner ear structures was assessed using a 4
      point scale (scores 1-2 = insufficient; scores 3-4 = sufficient). RESULTS: Middle
      and inner ear contrast showed a near linear increase with tube tension reduction
      (r = -0.94/-0.88) and was highest at 80 kV. Tube tension had no influence on
      spatial resolution. Subjective image quality analysis showed significantly better
      scoring at lower tube tensions, with highest image quality at 80 kV. However,
      image quality improvement was most relevant for low-dose scans. CONCLUSIONS:
      Image contrast in the temporal bone is significantly higher at low tube tensions,
      leading to a better subjective image quality. Highest contrast and best quality
      were found at 80 kV. This image quality improvement might be utilized to further
      reduce the radiation dose in pediatric low-dose CT protocols.

PMID- 21947249
TI  - Reliability of MRI findings in candidates for lumbar disc prosthesis.
AB  - INTRODUCTION: Limited reliability data exist for localised magnetic resonance
      imaging (MRI) findings relevant to planning of treatment with lumbar disc
      prosthesis and later outcomes. We assessed the reliability of such findings in
      chronic low back pain patients who were accepted candidates for disc prosthesis.
      METHODS: On pretreatment MRI of 170 patients (mean age 41 years; 88 women), three
      experienced radiologists independently rated Modic changes, disc findings and
      facet arthropathy at L3/L4, L4/L5 and L5/S1. Two radiologists rerated 126
      examinations. For each MRI finding at each disc level, agreement was analysed
      using the kappa statistic and differences in prevalence across observers using a
      fixed effects model. RESULTS: All findings at L3/L4 and facet arthropathy at
      L5/S1 had a mean prevalence <10% across observers and were not further analysed,
      ensuring interpretable kappa values. Overall interobserver agreement was
      generally moderate or good (kappa 0.40-0.77) at L4-S1 for Modic changes, nucleus
      pulposus signal, disc height (subjective and measured), posterior high-intensity
      zone (HIZ) and disc contour, and fair (kappa 0.24) at L4/L5 for facet
      arthropathy. Posterior HIZ at L5/S1 and severely reduced subjective disc height
      at L4/L5 differed up to threefold in prevalence between observers (p < 0.0001).
      Intraobserver agreement was mostly good or very good (kappa 0.60-1.00).
      CONCLUSION: In candidates for disc prosthesis, mostly moderate interobserver
      agreement is expected for localised MRI findings.

PMID- 21947250
TI  - delta-Aminolevulinic acid and its methyl ester induce the formation of
      Protoporphyrin IX in cultured sensory neurones.
AB  - Application of delta-aminolevulinic acid (ALA) or its methyl ester (MAL) onto
      cutaneous tumours increases intracellular Protoporphyrin IX (PpIX), serving as
      photosensitizer in photodynamic therapy (PDT). While PDT is highly effective as
      treatment of neoplastic skin lesions, it may induce severe pain in some patients.
      Here, we investigated ALA and MAL uptake and PpIX formation in sensory neurones
      as potential contributor to the pain. PpIX formation was induced in cultured
      sensory neurones from rat dorsal root ganglion by incubation with ALA or MAL.
      Using inhibitors of GABA transporters (GAT), a pharmacological profile of ALA and
      MAL uptake was assessed. GAT mRNA expression in the cultures was determined by RT
      PCR. Cultured sensory neurones synthesised Protoporphyrin IX (PpIX) from
      extracellularly administered ALA and MAL. PpIX formation was dose- and time
      dependent with considerably different kinetics for both compounds. While partial
      inhibition occurred using L-arginine, PpIX formation from both ALA and MAL could
      be fully blocked by the GABA-Transporter (GAT)-2/3 inhibitor (S)-SNAP 5114 with
      similar K (i) (ALA: 195 +/- 6 MUM; MAL: 129 +/- 13 MUM). GAT-1 and GAT-3 could be
      detected in sensory neurons using RT-PCR on mRNA level and using [3H]-GABA uptake
      on protein level. Cultured sensory neurones take up ALA and MAL and synthesize
      PpIX from both, enabling a direct impact of photodynamic therapy on cutaneous
      free nerve endings. The pharmacological profile of ALA and MAL uptake in our test
      system was very similar and suggests uptake via GABA and amino acid transporters.

PMID- 21947251
TI  - Characterization of a novel, brain-penetrating CB1 receptor inverse agonist:
      metabolic profile in diet-induced obese models and aspects of central activity.
AB  - Pharmacologic antagonism of cannabinoid 1 receptors (CB1 receptors) in the
      central nervous system (CNS) suppresses food intake, promotes weight loss, and
      improves the metabolic profile. Since the CB1 receptor is expressed both in the
      CNS and in peripheral tissues, therapeutic value may be gained with CB1 receptor
      inverse agonists acting on receptors in both domains. The present report examines
      the metabolic and CNS actions of a novel CB1 receptor inverse agonist, compound
      64, a 1,5,6-trisubstituted pyrazolopyrimidinone. Compound 64 showed similar or
      superior binding affinity, in vitro potency, and pharmacokinetic profile compared
      to rimonabant. Both compounds improved the metabolic profile in diet-induced
      obese (DIO) rats and obese cynomolgus monkeys. Weight loss tended to be greater
      in compound 64-treated DIO rats compared to pair-fed counterparts, suggesting
      that compound 64 may have metabolic effects beyond those elicited by weight loss
      alone. In the CNS, reversal of agonist-induced hypothermia and hypolocomotion
      indicated that compound 64 possessed an antagonist activity in vivo. Dosed alone,
      compound 64 suppressed extinction of conditioned freezing (10 mg/kg) and rapid
      eye movement (REM) sleep (30 mg/kg), consistent with previous reports for
      rimonabant, although for REM sleep, compound 64 was greater than threefold less
      potent than for metabolic effects. Together, these data suggested that (1)
      impairment of extinction learning and REM sleep suppression are classic,
      centrally mediated responses to CB1 receptor inverse agonists, and (2) some
      separation may be achievable between central and peripheral effects with brain
      penetrating CB1 receptor inverse agonists while maintaining metabolic efficacy.
      Furthermore, chronic treatment with compound 64 contributes to evidence that
      peripheral CB1 receptor blockade may yield beneficial outcomes that exceed those
      elicited by weight loss alone.

PMID- 21947252
TI  - Bp5250 inhibits vascular endothelial growth factor-induced angiogenesis and HIF
      1alpha expression on endothelial cells.
AB  - Angiogenesis plays a critical role in many physiological and pathological
      phenomena. A number of anti-angiogenesis drugs have been used in the clinical
      treatment of diseases such as malignant tumors and macular degeneration. Vascular
      endothelial growth factor (VEGF), the major pro-angiogenesis factor, is known to
      stimulate various steps of endothelial angiogenic activity, such as
      proliferation, migration, and differentiation into vessel-like tubes. In this
      study, we tested the effects of bp5250 on the angiogenesis of human umbilical
      endothelial cells (HUVECs). Bp5250 suppressed VEGF-induced endothelial cell
      proliferation by triggering apoptosis, and reduced endothelial cell migration
      toward VEGF. Bp5250 also decreased VEGF-stimulated tube formation and rat aortic
      ring sprouting on Matrigel in a concentration-dependent manner. In the VEGF
      activated signaling pathways, bp5250 decreased the phosphorylation of ERK, p38,
      PI3K-AKT, Src, and FAK and also reduced the activation of the cytoskeleton
      associated Rho family, all in a concentration-dependent manner. Bp5250 also
      attenuated the hypoxia-inducible factor-1alpha (HIF-1alpha) and VEGF-stimulated
      mRNA expression of HUVECs under the hypoxic condition. In vivo, angiogenesis was
      restrained by a daily intraperitoneal administration of bp5250 in a dose
      dependent manner (1-3 mg/kg/d) in the Matrigel plug implantation assay. These
      results indicate that bp5250 is a potential candidate for developing anti
      angiogenic agents.

PMID- 21947253
TI  - Rilmenidine improves hepatic steatosis through p38-dependent pathway to higher
      the expression of farnesoid X receptor.
AB  - The nuclear receptor farnesoid X receptor (FXR) regulates pathways in lipid,
      glucose, and energy metabolism. Activation of FXR in mice significantly improved
      high-fat diet-induced hepatic steatosis. It has been reported that activation of
      imidazoline I-1 receptor by rilmenidine increases the expression of FXR in human
      hepatoma cell line, Hep G2 cell, to regulate the target genes relating to lipid
      metabolism; activation of FXR by rilmenidine exerts an antihyperlipidemic action.
      However, signals for this action of rilmenidine are still unknown. In the present
      study, hepatic steatosis induced in mice by high-fat diet was improved by
      rilmenidine after intraperitoneal injection at 1 mg/kg daily for 12 weeks. Also,
      mediation of I-1 receptors was identified using the specific antagonist efaroxan.
      Moreover, rilmenidine decreased the oleic acid-induced lipid accumulation in Hep
      G2 cells. Otherwise, rilmenidine increased the phosphorylation of p38 to increase
      the expression of FXR. Deletion of calcium ions by BAPTA-AM reversed the
      rilmenidine-induced p38 phosphorylation. In conclusion, we suggest that
      rilmenidine activates I-1 receptor to increase intracellular calcium ions that
      may enhance the phosphorylation of p38 to higher the expression of FXR for
      improvement of hepatic steatosis in both animals and cells.

PMID- 21947254
TI  - The effects of modulating eNOS activity and coupling in ischemia/reperfusion
      (I/R).
AB  - The in vivo role of endothelial nitric oxide synthase (eNOS) uncoupling mediating
      oxidative stress in ischemia/reperfusion (I/R) injury has not been well
      established. In vitro, eNOS coupling refers to the reduction of molecular oxygen
      to L-arginine oxidation and generation of L-citrulline and nitric oxide NO
      synthesis in the presence of an essential cofactor, tetrahydrobiopterin (BH(4)).
      Whereas uncoupled eNOS refers to that the electron transfer becomes uncoupled to
      L-arginine oxidation and superoxide is generated when the dihydrobiopterin
      (BH(2)) to BH(4) ratio is increased. Superoxide is subsequently converted to
      hydrogen peroxide (H(2)O(2)). We tested the hypothesis that promoting eNOS
      coupling or attenuating uncoupling after I/R would decrease H(2)O(2)/increase NO
      release in blood and restore postreperfused cardiac function. We combined BH(4)
      or BH(2) with eNOS activity enhancer, protein kinase C epsilon (PKC epsilon)
      activator, or eNOS activity reducer, PKC epsilon inhibitor, in isolated rat
      hearts (ex vivo) and femoral arteries/veins (in vivo) subjected to I(20 min)/R(45
      min). When given during reperfusion, PKC epsilon activator combined with BH(4),
      not BH(2), significantly restored postreperfused cardiac function and decreased
      leukocyte infiltration (p < 0.01) while increasing NO (p < 0.05) and reducing
      H(2)O(2) (p < 0.01) release in femoral I/R veins. These results provide indirect
      evidence suggesting that PKC epsilon activator combined with BH(4) enhances
      coupled eNOS activity, whereas it enhanced uncoupled eNOS activity when combined
      with BH(2). By contrast, the cardioprotective and anti-oxidative effects of the
      PKC epsilon inhibitor were unaffected by BH(4) or BH(2) suggesting that
      inhibition of eNOS uncoupling during reperfusion following sustained ischemia may
      be an important mechanism.

PMID- 21947255
TI  - Iron oxyhydroxide nanoparticles formed by forced hydrolysis: dependence of phase
      composition on solution concentration.
AB  - Nanoparticles of single-phase lepidocrocite (gamma-FeOOH) and goethite (alpha
      FeOOH) have been synthesized by forced hydrolysis of ferric nitrate with no other
      additives, and the particles have been characterized by XRD, FT-IR and TEM. At
      low Fe(NO(3))(3) concentrations the hydrolysis product is predominantly gamma
      FeOOH, while at high concentrations it is alpha-FeOOH. These particles are
      nanometers in size and fall within narrow particle size distributions. The
      dependence of the oxyhydoxide phase on ferric nitrate concentration is attributed
      to two thermodynamic factors, the enthalpy of formation and the surface enthalpy
      of hydration at the oxide-water interface (which is a function of surface area).
      Two potential mechanisms for the phase-specific growth are proposed that explain
      the solution concentration dependence of the phase formed. Three other common
      nanoscale particles (alpha-Fe(2)O(3), Fe(3)O(4) and gamma-Fe(2)O(3)) have also
      been prepared by relatively simple thermal/chemical treatment of the gamma-FeOOH
      nanoparticles.

PMID- 21947257
TI  - The "Shaken Baby" syndrome: pathology and mechanisms.
AB  - The "Shaken Baby" syndrome (SBS) is the subject of intense controversy; the
      diagnosis has in the past depended on the triad of subdural haemorrhage (SDH),
      retinal haemorrhage and encephalopathy. While there is no doubt that infants do
      suffer abusive injury at the hands of their carers and that impact can cause
      catastrophic intracranial damage, research has repeatedly undermined the
      hypothesis that shaking per se can cause this triad. The term non-accidental head
      injury has therefore been widely adopted. This review will focus on the pathology
      and mechanisms of the three physiologically associated findings which constitute
      the "triad" and are seen in infants suffering from a wide range of non-traumatic
      as well as traumatic conditions. "Sub" dural bleeding in fact originates within
      the deep layers of the dura. The potential sources of SDH include: the bridging
      veins, small vessels within the dura itself, a granulating haemorrhagic membrane
      and ruptured intracranial aneurysm. Most neuropathologists do not routinely
      examine eyes, but the significance of this second arm of the triad in the
      diagnosis of Shaken Baby syndrome is such that it merits consideration in the
      context of this review. While retinal haemorrhage can be seen clinically, dural
      and subarachnoid optic nerve sheath haemorrhage is usually seen exclusively by
      the pathologist and only rarely described by the neuroradiologist. The term
      encephalopathy is used loosely in the context of SBS. It may encompass anything
      from vomiting, irritability, feeding difficulties or floppiness to seizures,
      apnoea and fulminant brain swelling. The spectrum of brain pathology associated
      with retinal and subdural bleeding from a variety of causes is described. The
      most important cerebral pathology is swelling and hypoxic-ischaemic injury.
      Mechanical shearing injury is rare and contusions, the hallmark of adult
      traumatic brain damage, are vanishingly rare in infants under 1 year of age.
      Clefts and haemorrhages in the immediate subcortical white matter have been
      assumed to be due to trauma but factors specific to this age group offer other
      explanations. Finally, examples of the most common causes of the triad
      encountered in clinical diagnostic and forensic practice are briefly annotated.

PMID- 21947258
TI  - Removal of the potent greenhouse gas NF3 by reactions with the atmospheric
      oxidants O(1D), OH and O3.
AB  - Nitrogen trifluoride, NF(3), a trace gas of purely anthropogenic origin with a
      large global warming potential is accumulating in the Earth's atmosphere. Large
      uncertainties are however associated with its atmospheric removal rate. In this
      work, experimental and theoretical kinetic tools were used to study the reactions
      of NF(3) with three of the principal gas-phase atmospheric oxidants: O((1)D), OH
      and O(3). For reaction (R2) with O((1)D), rate coefficients of k(2)(212-356 K) =
      (2.0 +/- 0.3) * 10(-11) cm(3) molecule(-1) s(-1) were obtained in direct
      competitive kinetics experiments, and experimental and theoretical evidence was
      obtained for F-atom product formation. These results indicate that whilst
      photolysis in the stratosphere remains the principal fate of NF(3), reaction with
      O((1)D) is significant and was previously underestimated in atmospheric lifetime
      calculations. Experimental evidence of F-atom production from 248 nm photolysis
      of NF(3) was also obtained, indicating that quantum yields for NF(3) destruction
      remain significant throughout the UV. No evidence was found for reaction (R3) of
      NF(3) with OH indicating that this process makes little or no contribution to
      NF(3) removal from the atmosphere. An upper-limit of k(3)(298 K) < 4 * 10(-16)
      cm(3) molecule(-1) s(-1) was obtained experimentally; theoretical analysis
      suggests that the true rate coefficient is more than ten orders of magnitude
      smaller. An upper-limit of k(4)(296 K) < 3 * 10(-25) cm(3) molecule(-1) s(-1) was
      obtained in experiments to investigate O(3) + NF(3) (R4). Altogether these
      results underpin calculations of a long (several hundred year) lifetime for
      NF(3). In the course of this work rate coefficients (in units of 10(-11) cm(3)
      molecule(-1) s(-1)) for removal of O((1)D) by n-C(5)H(12), k(6) = (50 +/- 5) and
      by N(2), k(7) = (3.1 +/- 0.2) were obtained. Uncertainties quoted throughout are
      2sigma precision only.

PMID- 21947256
TI  - Newborn screening and renal disease: where we have been; where we are now; where
      we are going.
AB  - Newborn screening (NBS) has rapidly changed since its origins in the 1960s.
      Beginning with a single condition, then a handful in the 1990 s, NBS has expanded
      in the past decade to allow the detection of many disorders of amino-acid,
      organic-acid, and fatty-acid metabolism. These conditions often present with
      recurrent acute attacks of metabolic acidosis, hypoglycemia, liver failure, and
      hyperammonemia that may be prevented with initiation of early treatment. Renal
      disease is an important component of these disorders and is a frequent source of
      morbidity. Hemodialysis is often required for hyperammonemia in the organic
      acidemias and urea-cycle disorders. Rhabdomyolysis with renal failure is a
      frequent complication in fatty-acid oxidation disorders. Newer screening methods
      are under investigation to detect lysosomal storage diseases, primary
      immunodeficiencies, and primary renal disorders. These advances will present many
      challenges to nephrologists and pediatricians with respect to closely monitoring
      and caring for children with such disorders.

PMID- 21947259
TI  - The aggressiveness of murine lymphomas selected in vivo by growth rate correlates
      with galectin-1 expression and response to cyclophosphamide.
AB  - Although lymphomas account for almost half of blood-derived cancers that are
      diagnosed each year, the causes of new cases are poorly understood, as reflected
      by the relatively few risk factors established. Galectin-1, an immunoregulatory
      beta-galactoside-binding protein, has been widely associated with tumor-immune
      escape. The aim of the present work was to study the relationship between tumor
      growth rate, aggressiveness, and response to cyclophosphamide (Cy) therapy with
      regard to Gal-1 expression in murine T-cell lymphoma models. By means of a
      disruptive selection process for tumor growth rate, we generated two lymphoma
      variants from a parental T-cell lymphoma, which have unique characteristics in
      terms of tumor growth rate, spontaneous regression, metastatic capacity, Gal-1
      expression and sensitivity to Cy therapy. Here, we show that Gal-1 expression
      strongly correlates with tumor growth rate, metastatic capacity and response to
      single-dose Cy therapy in T-cell lymphoma models; this association might have
      important consequences for evaluating prognosis and treatments of this type of
      tumors.

PMID- 21947260
TI  - Rhesus monkey TRIM5alpha has distinct HIV-1 restriction activity among different
      mammalian cell lines.
AB  - Rhesus monkey TRIM5alpha (TRIM5alpha(rh)), a member of the tripartite motif
      (TRIM) family, was identified as the main restriction factor responsible for
      resistance of old world monkey cells to HIV-1 infection. However, the precise
      mechanism of HIV-1 infection inhibition by TRIM5alpha remains elusive and appears
      to be related to some cellular cofactors. Here we reported that TRIM5alpha(rh)
      can significantly reduce the infection efficiency of VSV-G pseudotyped HIV-1/MA
      YFP virus in human epithelial carcinoma (HeLa) cells, moderately reduce in
      porcine kidney (PK-15) cells and have no effect on the pseudotyped virus
      infection in Madin-Darby canine kidney (MDCK) cells. Furthermore, we found that
      the different HIV-1 restriction activities have no relation with the
      intracellular localization of TRIM5alpha(rh). These results indicate that the
      cellular environment is very important for the efficient anti-HIV-1 activity of
      TRIM5alpha(rh). We speculate that some unknown factors required for HIV-1
      infection inhibition activity are adequately expressed in HeLa cells,
      inadequately expressed in PK-15 cells and absent in MDCK cells.

PMID- 21947261
TI  - [Recurrence prevention of kidney stone disease].
AB  - In each urolithiasis patient the individual risk for recurrence determines the
      need for specific medical treatment. Therefore, a brief evaluation of the risk
      status after stone passage is mandatory to define patients at high risk for
      recurrence. Only one quarter of all urolithiasis patients are at high risk or
      suffer from severe metabolic disorders, which both demand further metabolic work
      up prior to medical therapy. However, the other three quarters benefit
      sufficiently from general preventive measures, such as high fluid intake, well
      balanced mixed diet and lifestyle changes. This article summarizes the recent
      recommendations for stone-specific recurrence prevention, discusses the different
      pharmacological treatment options and sketches the follow-up concept for high
      risk patients with ongoing medication.

PMID- 21947262
TI  - [Secondary and tertiary prevention of urological tumors].
AB  - The amount and quality of available data on secondary and tertiary prevention of
      urological tumors are to a large extent unsatisfactory. In the areas of nutrition
      and supplementary diet the consumption of tomatoes and especially tomato products
      could have a beneficial effect on the course of the disease for patients with
      prostate cancer, whereas there is evidence that the consumption of foodstuffs
      containing calcium (milk and milk products) and linolenic acid as well as a fat
      rich diet accelerate tumor progression. Despite as yet unsatisfactory data, men
      with urothelial tumors or prostate cancer should abstain from smoking and
      undertake sports activities. For medicinal measures the administration of 5-alpha
      reductase inhibitors and bone-promoting substances for patients with prostate
      cancer are under discussion. The effectiveness of the substances zoledronate and
      denosumab has been demonstrated in prospective randomized studies. The authors
      recommend that the scientifically neglected field of tertiary prevention of
      urological tumors should in future be included as a core factor of scientific
      investigations.

PMID- 21947263
TI  - The Xist RNA A-repeat comprises a novel AUCG tetraloop fold and a platform for
      multimerization.
AB  - X-chromosome inactivation (XCI) in female mammals depends on the noncoding RNA X
      inactivation specific transcript (Xist). The mechanism of chromosome-wide
      silencing by Xist is poorly understood. While it is established that the 5'
      region of Xist RNA, comprising the A-repeats and holding 7.5-8.5 copies of a
      conserved 26-mer sequence, is essential for Xist-mediated silencing, high
      resolution structural information for the A-repeats is not available. Here, we
      report the three-dimensional solution structure of a 14-mer hairpin in the 5'
      region of a human A-repeat. This hairpin is remarkably stable and adopts a novel
      AUCG tetraloop fold, the integrity of which is required for silencing. We show
      that, contrary to previous predictions, the 3' region of single or tandem A
      repeats mediates duplex formation in vitro. Significantly, mutations in this
      region disrupt the inter-repeat duplex formation in vitro and abrogate the
      silencing function of Xist A-repeats in vivo. Our data suggest that the complete
      A-repeat region may be stabilized by inter-repeat duplex formation and, as such,
      may provide a platform for multimerization and specific recognition of the AUCG
      tetraloops by trans-acting factors.

PMID- 21947264
TI  - The role of the 5'-3' exoribonuclease XRNA in transcriptome-wide mRNA
      degradation.
AB  - The steady-state level of each mRNA in a cell is a balance between synthesis and
      degradation. Here, we use high-throughput RNA sequencing (RNASeq) to determine
      the relationship between mRNA degradation and mRNA abundance on a transcriptome
      wide scale. The model organism used was the bloodstream form of Trypanosoma
      brucei, a protist that lacks regulation of RNA polymerase II initiation. The mRNA
      half-lives varied over two orders of magnitude, with a median half-life of 13 min
      for total (rRNA-depleted) mRNA. Data for poly(A)+ RNA yielded shorter half-lives
      than for total RNA, indicating that removal of the poly(A) tail was usually the
      first step in degradation. Depletion of the major 5'-3' exoribonuclease, XRNA,
      resulted in the stabilization of most mRNAs with half-lives under 30 min. Thus,
      on a transcriptome-wide scale, degradation of most mRNAs is initiated by
      deadenylation. Trypanosome mRNA levels are strongly influenced by gene copy
      number and mRNA half-life: Very abundant mRNAs that are required throughout the
      life-cycle may be encoded by multicopy genes and have intermediate-to-long half
      lives; those encoding ribosomal proteins, with one to two gene copies, are
      exceptionally stable. Developmentally regulated transcripts with a lower
      abundance in the bloodstream forms than the procyclic forms had half-lives around
      the median, whereas those with a higher abundance in the bloodstream forms than
      the procyclic forms, such as those encoding glycolytic enzymes, had longer half
      lives.

PMID- 21947265
TI  - Staphylolysin is an effective therapeutic agent for Staphylococcus aureus
      experimental keratitis.
AB  - BACKGROUND: Therapy of S. aureus keratitis is increasingly challenging due to
      emerging resistant strains. Staphylolysin (LasA protease) is a staphylolytic
      endopeptidase secreted by Pseudomonas aeruginosa. The purpose of the current
      study was to study the effect of treatment with staphylolysin on experimental
      keratitis caused by various Staphylococcus aureus strains. METHODS: The
      therapeutic effect was studied in a keratitis model induced in rabbits by
      intrastromal injections of 10(3) S. aureus cells of three different methicillin
      resistant S. aureus (MRSA) strains and one methicillin-susceptible S. aureus
      strain (MSSA). Topical treatment with either staphylolysin or bovine serum
      albumin (BSA; control) was applied every half hour for 5 h, starting at 4 h after
      infection. Corneas were removed for bacterial quantification. Histopathological
      analysis was performed on MSSA-infected rabbits, killed at either one or 84 h
      after completion of treatment and on uninfected eyes 1 h after treatment
      termination. RESULTS: The number of bacteria in the staphylolysin-treated corneas
      was significantly reduced in all infections with the four S. aureus strains
      studied as compared to controls: the staphylolysin-treated eyes infected with
      MRSA strains were either completely sterilized or showed a 3-4 orders of
      magnitude decrease in the number of cfu/cornea (p = 0.004 to 0.005); all of the
      staphylolysin-treated MSSA-infected eyes were sterile. Histopathological analysis
      of the methicillin-sensitive (MSSA) strain-infected eyes at 84 h after completion
      of treatment showed moderate inflammation in the staphylolysin-treated eyes as
      compared with extensive abscess formation in the control group. The uninfected
      corneas showed only mild stromal edema in both the staphylolysin and BSA-treated
      groups. CONCLUSIONS: Staphylolysin provided long-lasting protection against
      several strains of S. aureus, evident by both its strong anti-bacterial activity
      and beneficial histopathological results of treatment.

PMID- 21947266
TI  - Fundus autofluorescence and retinal structure as determined by spectral domain
      optical coherence tomography, and retinal function in retinitis pigmentosa.
AB  - BACKGROUND: To investigate the association between fundus autofluorescence (FAF)
      and retinal structure and function in retinitis pigmentosa (RP). METHODS: For
      image acquisition, HRA2 (Heidelberg Engineering) and 3D-OCT1000 (Topcon Corp.)
      were used. Based on FAF examination, 88 eyes of 44 RP patients were categorized
      into three types. The area within the hyperautofluorescent ring and the area of
      preserved retinal autofluorescence with FAF was calculated. The association
      between the pattern of FAF and the residual area of the junction between the
      inner and outer segments of the photoreceptors (IS/OS line), and the relationship
      between the area within hyperautofluorescent ring, the area of preserved retinal
      autofluorescence and the mean deviation (MD) of static perimetry were assessed.
      RESULTS: Twenty-four eyes were with preserved retinal autofluorescence without
      hyperautofluorescent ring, 54 eyes were with hyperautofluorescent ring and ten
      eyes were with abnormal foveal autofluorescence both in the fovea and the
      periphery of the 30 degrees  scan. In the first type, the IS/OS line was clearly
      detected. In the second type, the residual area of the partially distinct IS/OS
      line corresponded with the area within hyperautofluorescent ring with significant
      correlation between the area within hyperautofluorescent ring and the MD (R(2) =
      0.705, p < 0.001); however, there was no correlation between the area of
      preserved retinal autofluorescence and the MD, or between the area of preserved
      retinal autofluorescence and the area within hyperautofluorescent ring. In the
      third type, the IS/OS line was completely absent. CONCLUSIONS: The residual IS/OS
      line can be found in the area inside the hyperautofluorescent ring and correlates
      with residual visual function.

PMID- 21947267
TI  - Thrombin generation and activated protein C resistance in the absence of factor V
      Leiden correlates with the risk of recurrent venous thromboembolism in women aged
      18-65 years.
AB  - Identification of patients at high risk of recurrence after a first event of
      venous thromboembolism (VTE) remains difficult. Resistance to activated protein C
      (APC) is a known risk factor for VTE, but data on the risk of recurrence is
      controversial. We wanted to investigate whether APC resistance in the absence of
      factor V Leiden, determined with global coagulation test such as the thrombin
      generation assay, could be used as a marker for increased risk of recurrent VTE
      among women 18-65 years old after a first event of VTE. In a cohort of 243 women
      with a first event of VTE, plasma was collected after discontinuation of
      anticoagulant treatment and the patients were followed up for 46 months (median).
      Thrombin generation was measured via calibrated automated thrombography, at 1 pM
      and 10 pM of tissue factor (TF). In women without factor V Leiden (n=117),
      samples were analysed in the absence and in the presence of APC. Increase in ETP
      (endogenous thrombin potential) and peak height analysed in the presence of APC
      correlated significantly with higher risk of recurrence. At 1 pM, peak height
      correlated with increased risk of recurrence. In conclusion, high thrombin
      generation in the presence of APC, in women after a first event of VTE is
      indicative for an increased risk of a recurrence. We also found that thrombin
      generation at low TF (1 pM) is correlated with the risk of recurrence. Our data
      suggest that APC resistance in the absence of factor V Leiden is a risk factor
      for recurrent VTE.

PMID- 21947268
TI  - Adjuvant immunotherapy of C6 glioma in rats with pertussis toxin.
AB  - PURPOSE: In spite of the recent advances in surgery and antitumor drugs, the
      brain tumors, like glioblastoma, have shown a poor prognosis. The aim of this
      study was to determine the effect of pertussis toxin (PTx) as immunomodulatory
      molecule on glial tumors induced by C6 glioma cells. METHODS: Given the
      pleiotropic effect of PTx on the immune system, we analyzed the effect of PTx on
      CD4+/CD25+/FoxP3+ (Treg) cells like as immunotherapeutic adjuvant. Thirty rats
      with a glial tumor of 1.5 cm in diameter were separated in two groups: the first
      group was treated with PTx and the second group was non-treated (controls).
      Tumoral volume was measured weekly; tumor, blood and spleen were taken for
      analysis of subpopulations of T cells, apoptotic index and cytokine contents, in
      both groups. RESULTS: We observed a significant decrease in tumor volume in the
      PTx group; this was associated with a decreased in the number of Treg cells, in
      both spleen and tumor. The percentage of apoptotic cells was increased as
      compared with that of controls. The production of proinflammatory cytokines was
      increased in mRNA for IL-6 as well as a small increase in the mRNA expression of
      perforin and granzime in tumors from rats treated with PTx. No changes were found
      in the mRNA expression of MCP-1 and MIP-1alpha. CONCLUSION: These results suggest
      that PTx could be an immunotherapeutic adjuvant in the integral therapy against
      glial tumors.

PMID- 21947269
TI  - Quantitative methylation analysis of HOXA3, 7, 9, and 10 genes in glioma:
      association with tumor WHO grade and clinical outcome.
AB  - PURPOSE: The purpose of this study was to determine whether specific HOXA
      epigenetic signatures could differentiate glioma with distinct biological,
      pathological, and clinical characteristics. METHODS: We evaluated HOXA3, 7, 9,
      and 10 methylation in 63 glioma samples by MassARRAY and pyrosequencing. RESULTS:
      We demonstrated the direct statistical correlation between the level of
      methylation of all HOXA genes examined and WHO grading. Moreover, in glioblastoma
      patients, higher level of HOXA9 and HOXA10 methylation significantly correlated
      with increased survival probability (HOXA9-HR: 0.36, P = 0.007; HOXA10-HR: 0.46,
      P = 0.045; combined HOXA9 and 10-HR 0.28, P = 0.004). CONCLUSIONS: This study
      identifies HOXA3, 7, 9, and 10 as methylation targets mainly in high-grade glioma
      and hypermethylation of the HOXA9 and 10 as prognostic factor in glioblastoma
      patients. Our data indicate that these epigenetic changes may be biomarkers of
      clinically different subgroups of glioma patients that could eventually benefit
      from personalized therapeutic strategies.

PMID- 21947270
TI  - Tubulointerstitial injury and the progression of chronic kidney disease.
AB  - In chronic kidney disease (CKD), once injury from any number of disease processes
      reaches a threshold, there follows an apparently irreversible course toward
      decline in kidney function. The tubulointerstitium may play a key role in this
      common progression pathway. Direct injury, high metabolic demands, or stimuli
      from various other forms of renal dysfunction activate tubular cells. These, in
      turn, interact with interstitial tissue elements and inflammatory cells, causing
      further pathologic changes in the renal parenchyma. The tissue response to these
      changes thus generates a feed-forward loop of kidney injury and progressive loss
      of function. This article reviews the mechanisms of this negative cycle mediating
      CKD.

PMID- 21947272
TI  - Mycophenolate mofetil for steroid-dependent nephrotic syndrome: a phase II
      Bayesian trial.
AB  - Mycophenolate mofetil (MMF) has emerged as a new therapeutic option in steroid
      dependent nephrotic syndrome (SDNS). We conducted a phase II Bayesian trial of
      MMF in children with SDNS. Phase II trials, usually single-arm studies,
      investigate the effect of new treatments. Standard Fleming's procedure relies on
      observed results (relapse rate during the trial), whereas Bayesian approach
      combines observed results with prior information (expected relapse rate according
      to prior studies and clinical experience). All patients were required to have
      received prior alkylating-agent treatment. Sixty-seven percent of them had also
      received levamisole. Patients received MMF (1,200 mg/m(2)/day) and prednisone
      according to a defined schedule [reduction of alternate-day (e.o.d) dose to 50%
      of pre-MMF dose at 3 months, 25% at 6 months]. Twenty-four children (median age
      6.0 years, 2.8-14.4) entered the study and 23 completed it. Bayesian analysis
      showed that adding four patients would not change significance of results,
      allowing stopping inclusions. Four patients relapsed during the first 6 months
      (estimated probability 17.6%, 95% credibility interval: 5.4-35.0%) and two at
      months 8 and 11.5. In the 19 patients free of relapse during the first 6 months,
      median (Q1-Q3) prednisone maintenance dose decreased from 25 (10-44) to 9 (7.5
      11.2) mg/m(2) e.o.d (p < 0.001) and cumulative dose from 459 (382-689) to 264
      (196-306) mg/m(2)/month (p < 0.001) before and on MMF respectively. Pre-MMF
      patient characteristics and MMF pharmacokinetics did not differ between patients
      with or without relapse. MMF reduces relapse rate and steroid dose in children
      with SDNS and should be proposed before cyclosporine and cyclophosphamide.

PMID- 21947273
TI  - Renal outcome in long-term survivors from severe acute kidney injury in
      childhood.

PMID- 21947271
TI  - Renal tumours: long-term outcome.
AB  - Childhood cancer is rare, with an incidence of 100 new cases per million children
      and with renal tumours contributing 7% of cases. The introduction of
      multimodality treatment, surgery, radiotherapy and chemotherapy, has led to an
      exponential increase in the 5-year survival rate to >80%. However, this
      successful treatment has led to the development of late adverse effects. These
      treatment-related effects can cause premature deaths and increased morbidity
      compared with patients' peers. Radiation causes damage to tissue and organs
      within the radiation field, affecting growth and function, and is largely
      responsible for the leading cause of death, namely, second malignant neoplasms.
      Another important late effect is cardiac dysfunction due to anthracycline use
      with or without cardiac radiation. In addition, a few patients have genetic
      abnormalities predisposing to Wilms tumour development, which result in renal
      dysfunction in the long term and may be exacerbated by cancer treatment regimens.
      Awareness of late consequences of cancer treatment is important, as early
      recognition can improve outcome. When presented with a patient with a history of
      renal tumours, it is vital to enquire about previous treatment to understand
      whether it is relevant to the presenting problem.

PMID- 21947275
TI  - Calcification of the cartilaginous Eustachian tube.

PMID- 21947276
TI  - Structural analysis of intrinsically disordered proteins by small-angle X-ray
      scattering.
AB  - Small-angle scattering of X-rays (SAXS) is an established method to study the
      overall structure and structural transitions of biological macromolecules in
      solution. For folded proteins, the technique provides three-dimensional low
      resolution structures ab initio or it can be used to drive rigid-body modeling.
      SAXS is also a powerful tool for the quantitative analysis of flexible systems,
      including intrinsically disordered proteins (IDPs), and is highly complementary
      to the high resolution methods of X-ray crystallography and NMR. Here we present
      the basic principles of SAXS and review the main approaches to the
      characterization of IDPs and flexible multidomain proteins using SAXS. Together
      with the standard approaches based on the analysis of overall parameters, a
      recently developed Ensemble Optimization Method (EOM) is now available. The
      latter method allows for the co-existence of multiple protein conformations in
      solution compatible with the scattering data. Analysis of the selected ensembles
      provides quantitative information about flexibility and also offers insights into
      structural features. Examples of the use of SAXS and combined approaches with
      NMR, X-ray crystallography, and computational methods to characterize completely
      or partially disordered proteins are presented.

PMID- 21947277
TI  - Reactive processes in gas phase Na(+)-iso-C3H7Cl collisions: experimental guided
      ion-beam and ab initio studies of the reactions on the ground singlet potential
      surface of the system up to 12.00 eV.
AB  - Reactive processes, taking place when sodium ions collide with neutral iso
      C(3)H(7)Cl molecules in the 0.02-12.00 eV range of energies in the center of mass
      frame, have been studied using an octopole radiofrequency guided-ion-beam
      apparatus developed in our laboratory. A dehydrohalogenation reaction channel
      leading to Na(C(3)H(6))(+) formation has been observed up to 1.00 eV while
      another process producing NaHCl(+) continues up to 4.00 eV. Furthermore,
      C(3)H(7)(+) formation resulting from decomposition of the reactants, ion-molecule
      adducts, has also been observed as well as its decomposition into C(2)H(3)(+) on
      increasing collision energy. Cross-section energy dependences for all these
      reactions have been obtained in absolute units. The ab initio electronic
      structure calculations have been done at the MP2 level for the colliding system
      ground singlet potential surface, giving information on the reactive surface main
      topological features. From the surface reactants side to the products' one,
      different potential wells and barriers have been characterized and their
      connectivity along the reaction evolution has been established using the
      intrinsic-reaction-coordinate method, thus interpreting the dynamical evolution
      of the reactants' collision complex to products. Experimental results demonstrate
      that NaHCl(+) can be produced via different channels. Reaction rate constants at
      308.2 K for both dehydrohalogenation reactions have been calculated from measured
      excitation functions. It has been also confirmed that the reactants adduct
      decomposition giving C(3)H(7)(+) and NaCl takes place on the same potential
      surface. A qualitative interpretation of the experimental results in terms of ab
      initio calculations is also given.

PMID- 21947278
TI  - Recombination and chemical energy accommodation coefficients from chemical
      dynamics simulations: O/O2 mixtures reacting over a beta-cristobalite (001)
      surface.
AB  - A microkinetic model is developed to study the reactivity of an O/O(2) gas
      mixture over a beta-cristobalite (001) surface. The thermal rate constants for
      the relevant elementary processes are either inferred from quasiclassical
      trajectory calculations or using some statistical approaches, resting on a
      recently developed interpolated multidimensional potential energy surface based
      on density functional theory. The kinetic model predicts a large molecular
      coverage at temperatures lower than 1000 K, in contrary to a large atomic
      coverage at higher temperatures. The computed atomic oxygen recombination
      coefficient, mainly involving atomic adsorption and Eley-Rideal recombination, is
      small and increases with temperature in the 700-1700 K range (0.01 < gamma(O) <
      0.02) in good agreement with experiments. In the same temperature range, the
      estimated chemical energy accommodation coefficient, the main contribution to
      which is the atomic adsorption process is almost constant and differs from unity
      (0.75 < beta(O) < 0.80).

PMID- 21947279
TI  - Plk1 phosphorylation of Orc2 promotes DNA replication under conditions of stress.
AB  - Polo-like kinase 1 (Plk1) plays pivotal roles in mitosis; however, little is
      known about its function in S phase. In this study, we show that inhibition of
      Plk1 impairs DNA replication and results in slow S-phase progression in cultured
      cancer cells. We have identified origin recognition complex 2 (Orc2), a member of
      the DNA replication machinery, as a Plk1 substrate and have shown that Plk1
      phosphorylates Orc2 at Ser188 in vitro and in vivo. Furthermore, Orc2-S188
      phosphorylation is enhanced when DNA replication is under challenge induced by
      ultraviolet, hydroxyurea, gemcitabine, or aphidicolin treatment. Cells expressing
      the unphosphorylatable mutant (S188A) of Orc2 had defects in DNA synthesis under
      stress, suggesting that this phosphorylation event is critical to maintain DNA
      replication under stress. To dissect the mechanism pertinent to this observation,
      we showed that Orc2-S188 phosphorylation associates with DNA replication origin
      and that cells expressing Orc2-S188A mutant fail to maintain the functional pre
      replicative complex (pre-RC) under DNA replication stress. Furthermore, the intra
      S-phase checkpoint is activated in Orc2-S188A-expressing cells to cause delay of
      S-phase progress. Our study suggests a novel role of Plk1 in facilitating DNA
      replication under conditions of stress to maintain genomic integrity.

PMID- 21947280
TI  - Osteoclast progenitors reside in the peroxisome proliferator-activated receptor
      gamma-expressing bone marrow cell population.
AB  - Osteoclasts are bone-resorbing cells essential for skeletal development,
      homeostasis, and regeneration. They derive from hematopoietic progenitors in the
      monocyte/macrophage lineage and differentiate in response to RANKL. However, the
      precise nature of osteoclast progenitors is a longstanding and important
      question. Using inducible peroxisome proliferator-activated receptor gamma
      (PPARgamma)-tTA TRE-GFP (green fluorescent protein) reporter mice, we show that
      osteoclast progenitors reside specifically in the PPARgamma-expressing
      hematopoietic bone marrow population and identify the quiescent PPARgamma(+)
      cells as osteoclast progenitors. Importantly, two PPARgamma-tTA TRE-Cre
      controlled genetic models provide compelling functional evidence. First, Notch
      activation in PPARgamma(+) cells causes high bone mass due to impaired osteoclast
      precursor proliferation. Second, selective ablation of PPARgamma(+) cells by
      diphtheria toxin also causes high bone mass due to decreased osteoclast numbers.
      Furthermore, PPARgamma(+) cells respond to both pathological and pharmacological
      resorption-enhancing stimuli. Mechanistically, PPARgamma promotes osteoclast
      progenitors by activating GATA2 transcription. These findings not only identify
      the long-sought-after osteoclast progenitors but also establish unprecedented
      tools for their visualization, isolation, characterization, and genetic
      manipulation.

PMID- 21947281
TI  - FOSL1 is integral to establishing the maternal-fetal interface.
AB  - Remodeling of uterine spiral arteries by trophoblast cells is a requisite process
      for hemochorial placentation and successful pregnancy. The rat exhibits deep
      intrauterine trophoblast invasion and accompanying trophoblast-directed vascular
      modification. The involvement of phosphatidylinositol 3 kinase (PI3K), AKT, and
      Fos-like antigen 1 (FOSL1) in regulating invasive trophoblast and hemochorial
      placentation was investigated using Rcho-1 trophoblast stem cells and rat models.
      Disruption of PI3K/AKT with small-molecule inhibitors interfered with the
      differentiation-dependent elaboration of a signature invasive-vascular remodeling
      trophoblast gene expression profile and trophoblast invasion. AKT isoform
      specific knockdown also affected the signature invasive-vascular remodeling
      trophoblast gene expression profile. Nuclear FOSL1 increased during trophoblast
      cell differentiation in a PI3K/AKT-dependent manner. Knockdown of FOSL1 disrupted
      the expression of a subset of genes associated with the invasive-vascular
      remodeling trophoblast phenotype, including the matrix metallopeptidase 9 gene
      (Mmp9). FOSL1 was shown to occupy regions of the Mmp9 promoter in trophoblast
      cells critical for the regulation of Mmp9 gene expression. Inhibition of FOSL1
      expression also abrogated trophoblast invasion, as assessed in vitro and
      following in vivo trophoblast-specific lentivirally delivered FOSL1 short hairpin
      RNA (shRNA). In summary, FOSL1 is a key downstream effector of the PI3K/AKT
      signaling pathway responsible for development of trophoblast lineages integral to
      establishing the maternal-fetal interface.

PMID- 21947282
TI  - SIRT1 deacetylates the DNA methyltransferase 1 (DNMT1) protein and alters its
      activities.
AB  - DNA methylation and histone acetylation/deacetylation are distinct biochemical
      processes that control gene expression. While DNA methylation is a common
      epigenetic signal that inhibits gene transcription, histone deacetylation
      similarly represses transcription but can be both an epigenetic and nonepigenetic
      phenomenon. Here we report that the histone deacetylase SIRT1 regulates the
      activities of DNMT1, a key enzyme responsible for DNA methylation. In mass
      spectrometry analysis, 12 new acetylated lysine sites were identified in DNMT1.
      SIRT1 physically associates with DNMT1 and can deacetylate acetylated DNMT1 in
      vitro and in vivo. Interestingly, deacetylation of different lysines on DNMT1 has
      different effects on the functions of DNMT1. For example, deacetylation of
      Lys1349 and Lys1415 in the catalytic domain of DNMT1 enhances DNMT1's
      methyltransferase activity, while deacetylation of lysine residues in the GK
      linker decreases DNMT1's methyltransferase-independent transcriptional repression
      function. Furthermore, deacetylation of all identified acetylated lysine sites in
      DNMT1 abrogates its binding to SIRT1 and impairs its capability to regulate cell
      cycle G(2)/M transition. Finally, inhibition of SIRT1 strengthens the silencing
      effects of DNMT1 on the expression of tumor suppressor genes ER-alpha and CDH1 in
      MDA-MB-231 breast cancer cells. Together, these results suggest that SIRT1
      mediated deacetylation of DNMT1 is crucial for DNMT1's multiple effects in gene
      silencing.

PMID- 21947283
TI  - Survival and differentiation of mammary epithelial cells in mammary gland
      development require nuclear retention of Id2 due to RANK signaling.
AB  - RANKL plays an essential role in mammary gland development during pregnancy.
      However, the molecular mechanism by which RANK signaling leads to mammary gland
      development is largely unknown. We report here that RANKL stimulation induces
      phosphorylation of Id2 at serine 5, which leads to nuclear retention of Id2. In
      lactating Id2Tg; RANKL(-/-) mice, Id2 was not phosphorylated and was localized in
      the cytoplasm. In addition, in lactating Id2(S5A)Tg mice, Id2(S5A) (with serine 5
      mutated to alanine) was exclusively localized in the cytoplasm of mammary
      epithelial cells (MECs), while endogenous Id2 was localized in the nucleus.
      Intriguingly, nuclear expression of Id2(S5A) rescued increased apoptosis and
      defective differentiation of MECs in RANKL(-/-) mice. Our results demonstrate
      that nuclear retention of Id2 due to RANK signaling plays a decisive role in the
      survival and differentiation of MECs during mammary gland development.

PMID- 21947284
TI  - Mammalian Ino80 mediates double-strand break repair through its role in DNA end
      strand resection.
AB  - Chromatin modifications/remodeling are important mechanisms by which cells
      regulate various functions through providing accessibility to chromatin DNA.
      Recent studies implicated INO80, a conserved chromatin-remodeling complex, in the
      process of DNA repair. However, the precise underlying mechanism by which this
      complex mediates repair in mammalian cells remains enigmatic. Here, we studied
      the effect of silencing of the Ino80 subunit of the complex on double-strand
      break repair in mammalian cells. Comet assay and homologous recombination repair
      reporter system analyses indicated that Ino80 is required for efficient double
      strand break repair. Ino80 association with chromatin surrounding double-strand
      breaks suggested the direct involvement of INO80 in the repair process. Ino80
      depletion impaired focal recruitment of 53BP1 but did not impede Rad51 focus
      formation, suggesting that Ino80 is required for the early steps of repair.
      Further analysis by using bromodeoxyuridine (BrdU)-labeled single-stranded DNA
      and replication protein A (RPA) immunofluorescent staining showed that INO80
      mediates 5'-3' resection of double-strand break ends.

PMID- 21947285
TI  - Hyperforin induces apoptosis of chronic lymphocytic leukemia cells through
      upregulation of the BH3-only protein Noxa.
AB  - We previously reported that hyperforin, a phloroglucinol purified from Hypericum
      perforatum, induces the mitochondrial pathway of caspase-dependent apoptosis in
      chronic lymphocytic leukemia (CLL) cells ex vivo, and that this effect is
      associated with upregulation of Noxa, a BH3-only protein of the Bcl-2 family.
      Here, we investigated the role of this upregulation in the pro-apoptotic activity
      of hyperforin in the cells of CLL patients and MEC-1 cell line. We found that the
      increase in Noxa expression is a time- and concentration-dependent effect of
      hyperforin occurring without change in Noxa mRNA levels. A post-translational
      regulation is suggested by the capacity of hyperforin to inhibit proteasome
      activity in CLL cells. Noxa silencing by siRNA reduces partially hyperforin
      elicited apoptosis. Furthermore, treatment with hyperforin, which has no effect
      on the expression of the prosurvival protein Mcl-1, induces the interaction of
      Noxa with Mcl-1 and the dissociation of Mcl-1/Bak complex, revealing that
      upregulated Noxa displaces the proapoptotic protein Bak from Mcl-1. This effect
      is accompanied with Bak activation, known to allow the release of apoptogenic
      factors from mitochondria. Our data indicate that Noxa upregulation is one of the
      mechanisms by which hyperforin triggers CLL cell apoptosis. They also favor that
      new agents capable of mimicking specifically the BH3-only protein Noxa should be
      developed for apoptosis-based therapeutic strategy in CLL.

PMID- 21947286
TI  - Reduced length of stay following hip and knee arthroplasty in Denmark 2000-2009:
      from research to implementation.
AB  - INTRODUCTION: Fast-track surgery is the combination of optimized clinical and
      organizational factors aiming at reducing convalescence and perioperative
      morbidity including the functional recovery resulting in reduced hospitalization.
      As the previous nationwide studies have demonstrated substantial variations in
      length of stay (LOS) following standardized operations such as total hip and knee
      arthroplasty (THA and TKA), this nationwide study was undertaken to evaluate the
      implementation process of fast-track THA and TKA in Denmark. MATERIALS AND
      METHODS: All hospitals in Denmark report to the National Patient Registry,
      linking the type of surgery and LOS with a unique individual social security
      number. This study is based on primary THA and TKA from a 5.5 million population
      from 2000 to the end of 2009. RESULTS: The number of performed primary unilateral
      THA and TKA has increased from around 7,200 in 2000 to 13,800 in 2009 with a
      concomitant reduction in LOS from median 10-11 days in 2000 to 4 days in 2009.
      CONCLUSION: Fast-track surgery has been successfully implemented in the
      orthopedic departments in Denmark through a multi-disciplinary educational and
      multi-institutional effort. These implementation principles may be transferred to
      other countries and other specialties.

PMID- 21947287
TI  - Results of forty two computer-assisted double level osteotomies for severe genu
      varum deformity.
AB  - PURPOSE: The goal of this article was to present the clinical and radiological
      results of 42 severe genu varum operated on between August 2001 and June 2010
      using computer navigation. METHODS: All the osteotomies were navigated using the
      Orthopilot(r) device (B-Braun-Aesculap, Tuttlingen, Germany). The procedure was
      performed such that after inserting the rigid bodies and calibrating the lower
      leg, we first made the femoral closing wedge osteotomy (from four to seven mm)
      which was fixed by an AO T-Plate, and then, after checking the residual varus,
      the tibial opening wedge osteotomy was made using a Biosorb(r) wedge (Tricalcium
      phosphate, SBM, Lourdes, France) and a plate (AO T-plate or C-plate). RESULTS:
      All the patients were assessed at a mean follow-up of 46 +/- 27 months (range, 12
      108). The mean Lysholm-Tegner score was 83.3 +/- 7.5 points (62-91) and the mean
      KOOS score was 95.1 +/- 3.2 points (89-100). Forty patients were satisfied (22)
      or very satisfied (18) with the result. Regarding the radiological results, the
      goal was reached in 92.7% of cases and the mean HKA angle was 181.83 degrees  +/-
      1.80 degrees  (177-185 degrees ). At that mid-term follow-up no patient had
      revision to a total knee arthroplasty. CONCLUSION: Computer-assisted double level
      osteotomy in severe genu varum is a reliable, reproducible, and accurate
      technique. This procedure, which is very delicate, especially in reaching pre
      operative objectives, is simplified by computer-assistance.

PMID- 21947288
TI  - Ethanol withdrawal-induced motor impairment in mice.
AB  - RATIONALE: Human ethanol withdrawal manifests as multiple behavioral deficits
      with distinct time courses. Most studies with mice index ethanol withdrawal
      severity with the handling-induced convulsion (HIC). Using the accelerating
      rotarod (ARR), we recently showed that ethanol withdrawal produced motor
      impairment. OBJECTIVES: This study aimed (a) to characterize further the ARR
      withdrawal trait, (b) to assess generalizability across additional behavioral
      assays, and (c) to test the genetic correlation between ethanol withdrawal ARR
      impairment and HICs. RESULTS: The severity of the ARR performance deficit depends
      on ethanol vapor dose and exposure duration, and lasts 1-4 days. Fatigue could
      not explain the deficits, which were also evident after intermittent exposure to
      ethanol vapor. Withdrawing mice were also impaired on a balance beam, but not on
      a static dowel or in foot slip errors per distance traveled in the parallel rod
      floor test, where they showed reduced locomotor activity. To assess genetic
      influences, we compared Withdrawal Seizure-Prone and -Resistant mice, genetically
      selected to express severe vs. mild withdrawal HICs, respectively. The ARR scores
      were approximately equivalent in all groups treated with ethanol vapor, though
      Withdrawal Seizure-Prone (WSP) mice may have displayed a slightly more severe
      deficit as control-treated WSP mice performed better than control-treated
      Withdrawal Seizure-Resistant mice. CONCLUSIONS: These studies show that ethanol
      withdrawal motor impairment is sensitive to a range of ethanol doses and lasts
      for several days. Multiple assays of behavioral impairment are affected, but the
      effects depend on the assay employed. Genetic contributions to withdrawal-induced
      ARR impairment appear largely distinct from those leading to severe or mild HICs.

PMID- 21947290
TI  - Peak oxygen uptake correlates with survival without clinical deterioration in
      ambulatory children with dilated cardiomyopathy.
AB  - BACKGROUND: Children stable at home with dilated cardiomyopathy remain at risk of
      death; there is evidence of survival benefit for transplantation out to 4 years
      postoperatively. The limited supply of donor organs makes risk stratification
      imperative, but although cardiopulmonary exercise test is well established as a
      powerful tool in adults with heart failure, no published studies have linked
      oxygen uptake to prognosis in children. METHODS AND RESULTS: Between 2001 and
      2009, using cardiopulmonary exercise test and echocardiography, we studied 82
      children (mean age, 13.5+/-2.3 years) with dilated cardiomyopathy. All were
      ambulatory, outpatients, and >120 cm in height. All children completed a symptom
      limited maximal exercise test. Resting left ventricular shortening fraction was
      20+/-9%; peak heart rate was 87+/-13% of predicted; peak oxygen uptake (VO(2))
      was 67+/-22% of predicted; and ventilatory efficiency was 32+/-8. Follow-up was
      available for 100% of the children, and was a mean of 32.3+/-7.5 months. Eighteen
      patients reached the defined clinical end point of death or listing for urgent
      heart transplantation. On univariate analysis, left ventricular shortening
      fraction, peak heart rate, peak VO(2), peak systolic blood pressure, and
      ventilatory efficiency were all associated with adverse outcome. On multivariable
      Cox analysis, only peak VO(2) (P=0.003) was associated with the study end point.
      Patients with a peak VO(2) <=62% of predicted had a higher 24-month event rate
      (50.6% versus 4.4%; hazard ratio, 10.78). CONCLUSIONS: We have demonstrated that
      a cardiopulmonary exercise test is feasible in ambulatory children with dilated
      cardiomyopathy who are >120 cm height and for the first time have linked peak
      VO(2) with outcome in children.

PMID- 21947289
TI  - Blood pressure targets recommended by guidelines and incidence of cardiovascular
      and renal events in the Ongoing Telmisartan Alone and in Combination With
      Ramipril Global Endpoint Trial (ONTARGET).
AB  - BACKGROUND: Hypertension treatment guidelines recommend that blood pressure (BP)
      be lowered to <140/90 mm Hg, but that a reduction to <130/80 mm Hg be adopted in
      patients at high cardiovascular (CV) risk. We investigated the CV and renal
      benefits associated with these BP targets in the high-CV-risk population of the
      Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial
      (ONTARGET). METHODS AND RESULTS: Patients were divided into 4 groups according to
      the proportion of in-treatment visits before the occurrence of an event (<25%
      >75%) in which BP was reduced to <140/90 or <130/80 mm Hg. After adjustment for
      demographic and clinical variables, a progressive increase in the proportion of
      visits in which BP was reduced to <140/90 or <130/80 mm Hg was associated with a
      progressive reduction in the risk of stroke, new onset of microalbuminuria or
      macroalbuminuria, and return to normoalbuminuria in albuminuric patients. An
      increased frequency of BP control to either target did not have any consistent
      effect on the adjusted risk of myocardial infarction and heart failure. The
      adjusted risk of CV events was reduced by increasing the frequency of BP control
      to <140/90 mm Hg, but not to <130/80 mm Hg. Similar findings were obtained for
      the achievement of the BP target in the visit preceding a CV event. CONCLUSION:
      The more frequent achievement of the BP targets recommended by guidelines led to
      cerebrovascular and renal protection, but did not increase cardiac protection.
      Overall, CV protection was favorably affected by the less tight but not by the
      tighter BP target. Clinical Trial Registration-URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00153101.

PMID- 21947291
TI  - Assessing adiposity: a scientific statement from the American Heart Association.

PMID- 21947292
TI  - Congenital heart defects and developmental and other psychiatric disorders: a
      Danish nationwide cohort study.
AB  - BACKGROUND: We examined the risk of psychiatric in-patient admissions and out
      patient visits among Danish patients with congenital heart defects (CHD). METHODS
      AND RESULTS: Using the Danish National Registry of Patients, we identified CHD
      patients born January 1, 1977, to January 1, 2002. For each patient, we randomly
      selected 10 population-comparison cohort members from the Danish Civil
      Registration System, matched by sex and birth year. We computed cumulative risk
      and hazard ratios (HRs) of time to first psychiatric in-patient admission or out
      patient visit identified in the Danish Psychiatric Central Registry and adjusted
      for parents' educational level and parents' psychiatric morbidity. We identified
      6927 CHD patients. At 15 years of age, the cumulative risk of psychiatric
      admissions or out-patient visits was 5.9% (95% confidence interval [CI], 5.2%
      6.6%) among CHD patients. The HRs for CHD patients and comparison cohort members
      aged 0 to 14 years were 1.8 (95% CI: 1.5-2.1) for males and 2.5 (95% CI: 2.0-3.1)
      for females. For patients aged 15 to 30 years, the HRs were 1.6 (95% CI: 1.2-2.0)
      for males and 1.0 (95% CI: 0.8-1.3) for females. Congenital heart defect
      patients, both with and without invasive therapeutic interventions or
      extracardiac defects or syndromes, had a higher risk of psychiatric in-patient
      admissions or out-patient visits than comparison cohort members. After
      restriction of the comparison cohort to patients with diabetes mellitus or asthma
      (n=2554), the HR was 1.41 (95% CI: 1.07-1.85) for patients aged 0 to 14 years and
      0.70 (95% CI: 0.52-0.94) for patients aged 15 to 30 years. CONCLUSION: Congenital
      heart disease patients with or without invasive therapeutic interventions are at
      increased risk of developmental and other psychiatric disorders, which seem to
      develop earlier than in patients with diabetes mellitus or asthma.

PMID- 21947293
TI  - Impact of exercise on heart rate recovery.
AB  - BACKGROUND: Abnormal heart rate recovery (HRR) has been shown to predict
      mortality. Although small studies have found that HRR can be improved with
      cardiac rehabilitation, it is unknown whether an improvement would affect
      mortality. The aim of this study was to determine whether HRR could be improved
      with cardiac rehabilitation and whether it would be predictive of mortality.
      METHODS AND RESULTS: We evaluated 1070 consecutive patients who underwent
      exercise stress testing before and after completion of a phase 2 cardiac
      rehabilitation program. Heart rate recovery, defined as the difference between
      heart rate at peak exercise and exactly 1 minute into the recovery period, and
      mortality were followed up as the primary end points. Of 544 patients with
      abnormal baseline HRR, 225 (41%) had normal HRR after rehabilitation. Of the
      entire cohort, 197 patients (18%) died. Among patients with an abnormal HRR at
      baseline, failure to normalize after rehabilitation predicted a higher mortality
      (P<0.001). After multivariable adjustment, the presence of an abnormal HRR at
      exit was predictive of death in all patients (hazard ratio, 2.15; 95% confidence
      interval 1.43-3.25). Patients with abnormal HRR at baseline who normalized
      afterward had survival rates similar to those of the group with normal HRR at
      baseline and after cardiac rehabilitation (P=0.143). CONCLUSIONS: Heart rate
      recovery improved after phase 2 cardiac rehabilitation in the overall cohort.
      There was a strong association of abnormal HRR at exit with all-cause mortality.
      Patients with abnormal HRR at baseline who normalized HRR with exercise had a
      mortality similar to that of individuals with baseline normal HRR.

PMID- 21947294
TI  - Pediatric pulmonary hypertension in the Netherlands: epidemiology and
      characterization during the period 1991 to 2005.
AB  - BACKGROUND: Incidence and prevalence rates for pediatric pulmonary hypertension
      (PH) and pulmonary arterial hypertension (PAH) are unknown. This study describes
      the nationwide epidemiological features of pediatric PH in the Netherlands during
      a 15-year period and the clinical course of pediatric PAH. METHODS AND RESULTS:
      Two registries were used to retrospectively identify children (0-17 years) with
      PH. Overall, 3263 pediatric patients were identified with PH due to left heart
      disease (n=160; 5%), lung disease/hypoxemia (n=253; 8%), thromboembolic disease
      (n=5; <1%), and transient (n=2691; 82%) and progressive (n=154; 5%) PAH.
      Transient PAH included persistent PH of the newborn and children with congenital
      heart defects (CHD) and systemic-to-pulmonary shunt, in whom PAH resolved after
      successful shunt correction. Progressive PAH mainly included idiopathic PAH
      (n=36; iPAH) and PAH associated with CHD (n=111; PAH-CHD). Pulmonary arterial
      hypertension associated with CHD represented highly heterogeneous subgroups.
      Syndromes were frequently present, especially in progressive PAH (n=60; 39%).
      Survival for PAH-CHD varied depending on the subgroups, some showing better and
      others showing worse survival than for iPAH. Survival of children with
      Eisenmenger syndrome appeared worse than reported in adults. For iPAH and PAH
      CHD, annual incidence and point prevalence averaged, respectively, 0.7 and 4.4
      (iPAH) and 2.2 and 15.6 (PAH-CHD) cases per million children. Compared to studies
      in adults, iPAH occurred less whereas PAH-CHD occurred more frequently.
      CONCLUSIONS: Pediatric PH is characterized by various age-specific diagnoses, the
      majority of which comprise transient forms of PAH. Incidence of pediatric iPAH is
      lower whereas incidence of pediatric PAH-CHD is higher than reported in adults.
      Pediatric PAH-CHD represents a heterogeneous group with highly variable clinical
      courses.

PMID- 21947296
TI  - Disruption of Na+,HCO3- cotransporter NBCn1 (slc4a7) inhibits NO-mediated
      vasorelaxation, smooth muscle Ca2+ sensitivity, and hypertension development in
      mice.
AB  - BACKGROUND: Disturbances in pH affect artery function, but the mechanistic
      background remains controversial. We investigated whether Na(+), HCO3-
      transporter NBCn1, by regulating intracellular pH(pH1), influences artery
      function and blood pressure regulation. METHODS AND RESULTS: Knockout of NBCn1 in
      mice eliminated Na+, HCO3- cotransport and caused a lower steady-state pH(i) in
      mesenteric artery smooth muscle and endothelial cells in situ evaluated by
      fluorescence microscopy. Using myography, arteries from NBCn1 knockout mice
      showed reduced acetylcholine-induced NO-mediated relaxations and lower rho-kinase
      dependent norepinephrine-stimulated smooth muscle Ca2+ sensitivity. Acetylcholine
      stimulated NO levels (electrode measurements) and N-nitro-l-arginine methyl ester
      sensitive l-arginine conversion (radioisotope measurements) were reduced in
      arteries from NBCn1 knockout mice, whereas relaxation to NO-donor S-nitroso-N
      acetylpenicillamine, acetylcholine-induced endothelial Ca2+ responses
      (fluorescence microscopy), and total and Ser-1177 phosphorylated endothelial NO
      synthase expression (Western blot analyses) were unaffected. Reduced NO-mediated
      relaxations in arteries from NBCn1 knockout mice were not rescued by superoxide
      scavenging. Phosphorylation of myosin phosphatase targeting subunit at Thr-850
      was reduced in arteries from NBCn1 knockout mice. Evaluated by an in vitro assay,
      rho-kinase activity was reduced at low pH. Without CO2/HCO3-, no differences in
      pH(i), contraction or relaxation were observed between arteries from NBCn1
      knockout and wild-type mice. Based on radiotelemetry and tail-cuff measurements,
      NBCn1 knockout mice were mildly hypertensive at rest, displayed attenuated blood
      pressure responses to NO-synthase and rho-kinase inhibition and were resistant to
      developing hypertension during angiotensin-II infusion. CONCLUSIONS:
      Intracellular acidification of smooth muscle and endothelial cells after knockout
      of NBCn1 inhibits NO-mediated and rho-kinase-dependent signaling in isolated
      arteries and perturbs blood pressure regulation.

PMID- 21947295
TI  - Cardiomyocyte-specific deletion of the vitamin D receptor gene results in cardiac
      hypertrophy.
AB  - BACKGROUND: A variety of studies carried out using either human subjects or
      laboratory animals suggest that vitamin D and its analogues possess important
      beneficial activity in the cardiovascular system. Using Cre-Lox technology we
      have selectively deleted the vitamin D receptor (VDR) gene in the cardiac myocyte
      in an effort to better understand the role of vitamin D in regulating myocyte
      structure and function. METHODS AND RESULTS: Targeted deletion of the exon 4
      coding sequence in the VDR gene resulted in an increase in myocyte size and left
      ventricular weight/body weight versus controls both at baseline and following a 7
      day infusion of isoproterenol. There was no increase in interstitial fibrosis.
      These knockout mice demonstrated a reduction in end-diastolic and end-systolic
      volume by echocardiography, activation of the fetal gene program (ie, increased
      atrial natriuretic peptide and alpha skeletal actin gene expression), and
      increased expression of modulatory calcineurin inhibitory protein 1 (MCIP1), a
      direct downstream target of calcineurin/nuclear factor of activated T cell
      signaling. Treatment of neonatal cardiomyocytes with 1,25-dihydroxyvitamin D
      partially reduced isoproterenol-induced MCIP1 mRNA and protein levels and MCIP1
      gene promoter activity. CONCLUSIONS: Collectively, these studies demonstrate that
      the vitamin D-VDR signaling system possesses direct, antihypertrophic activity in
      the heart. This appears to involve, at least in part, suppression of the
      prohypertrophic calcineurin/NFAT/MCIP1 pathway. These studies identify a
      potential mechanism to account for the reported beneficial effects of vitamin D
      in the cardiovascular system.

PMID- 21947297
TI  - Effect of hypoxia-inducible factor-1alpha gene therapy on walking performance in
      patients with intermittent claudication.
AB  - BACKGROUND: Hypoxia-inducible factor-1alpha (HIF-1alpha) is a transcriptional
      regulatory factor that orchestrates cellular responses to hypoxia. It increases
      collateral vessel growth and blood flow in models of hind-limb ischemia. This
      study tested whether intramuscular administration of Ad2/HIF-1alpha/VP16, an
      engineered recombinant type 2 adenovirus vector encoding constitutively active
      HIF-1alpha, improves walking time in patients with peripheral artery disease and
      intermittent claudication. METHODS AND RESULTS: Two hundred eighty-nine patients
      with claudication were randomized in a double-blind manner to 1 of 3 doses of
      Ad2/HIF-1alpha/VP16 (2*10(9), 2*10(10), or 2*10(11) viral particles) or placebo,
      administered by 20 intramuscular injections to each leg. Graded treadmill tests
      were performed at baseline and then 3, 6, and 12 months after treatment. The
      primary end point was the change in peak walking time from baseline to 6 months.
      The secondary end point was change in claudication onset time, and tertiary end
      points included changes in ankle-brachial index and quality-of-life assessments.
      Median peak walking time increased by 0.82 minutes (interquartile range, -0.05
      1.93 minutes) in the placebo group and by 0.82 minutes (interquartile range, 
      0.07-2.12 minutes), 0.28 minutes (interquartile range, -0.37-1.70 minutes), and
      0.78 minutes (interquartile range, -0.02-2.10 minutes) in the HIF-1alpha 2*10(9),
      2*10(10), and 2*10(11) viral particle groups, respectively (P=NS between placebo
      and each HIF-1alpha treatment group). There were no significant differences in
      claudication onset time, ankle-brachial index, or quality-of-life measurements
      between the placebo and each HIF-1alpha group. CONCLUSIONS: Gene therapy with
      intramuscular administration of Ad2/HIF-1alpha/VP16 is not an effective treatment
      for patients with intermittent claudication. Clinical Trial Registration-URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00117650.

PMID- 21947298
TI  - Myocardial structure, function, and scar in patients with type 1 diabetes
      mellitus.
AB  - BACKGROUND: We report relationships between cardiovascular disease risk factors
      and myocardial structure, function, and scar in patients with type 1 diabetes
      mellitus in the Diabetes Control and Complications Trial/Epidemiology of Diabetes
      Interventions and Complications (DCCT/EDIC) study. METHODS AND RESULTS: Cardiac
      magnetic resonance was obtained in 1017 patients with type 1 diabetes mellitus.
      Gadolinium cardiac magnetic resonance was also obtained in 741 patients. The mean
      age was 49+/-7 years; 52% were men; and mean duration of diabetes mellitus was
      28+/-5 years. Associations of cardiovascular disease risk factors with cardiac
      magnetic resonance parameters were examined with linear and logistic regression
      models. History of macroalbuminuria was positively associated with left
      ventricular mass (by 14.8 g), leading to a significantly higher ratio of left
      ventricular mass to end-diastolic volume (by 8%). Mean hemoglobin A(1c) levels
      over the preceding 22 years were inversely associated with end-diastolic volume (
      3.0 mL per unit mean hemoglobin A(1c) percent) and stroke volume (-2.3 mL per
      unit mean hemoglobin A(1c) percent) and positively related to the ratio of
      elevated left ventricular mass to end-diastolic volume (0.02 g/mL per unit). The
      overall prevalence of myocardial scar was 4.3% by cardiac magnetic resonance and
      1.4% by clinical adjudication of myocardial infarction. Both mean hemoglobin
      A(1c) (odds ratio, 1.5 [95% confidence interval, 1.0-2.2] per unit) and
      macroalbuminuria (odds ratio, 3.5 [95% confidence interval, 1.2-9.9]) were
      significantly associated with myocardial scar and traditional cardiovascular
      disease risk factors. CONCLUSIONS: In addition to traditional cardiovascular
      disease risk factors, elevated mean hemoglobin A(1c) and macroalbuminuria were
      significantly associated with alterations in left ventricular structure and
      function. The prevalence of myocardial scar was 4.3% in this subcohort of
      DCCT/EDIC participants with relatively preserved renal function. Clinical Trial
      Registration-URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00360893
      and NCT00360815.

PMID- 21947299
TI  - ANTHOCYANIN1 from Solanum chilense is more efficient in accumulating anthocyanin
      metabolites than its Solanum lycopersicum counterpart in association with the
      ANTHOCYANIN FRUIT phenotype of tomato.
AB  - Anthocyanins are flavonoid metabolites contributing attractive colors and
      antioxidant qualities to the human diet. Accordingly, there is a growing interest
      in developing crops enriched with these compounds. Fruits of the cultivated
      tomato, Solanum (S.) lycopersicum, do not normally produce high levels of
      anthocyanins. However, several wild tomato species yield anthocyanin-pigmented
      fruits, and this trait has been introgressed into the cultivated tomato. Two
      genes encoding homologous R2R3 MYB transcription factors, termed ANT1 and AN2,
      were previously genetically implicated in anthocyanin accumulation in tomato
      fruit peels of the ANTHOCYANIN FRUIT (AFT) genotype originating from S. chilense.
      Here we compared transgenic tomato plants constitutively over-expressing the S.
      lycopersicum (35S::ANT1 ( L ) ) or the S. chilense (35S::ANT1 ( C )) allele, and
      show that each displayed variable levels of purple pigmentation in vegetative as
      well as reproductive tissues. However, 35S::ANT1 ( C ) was significantly more
      efficient in producing anthocyanin pigments, attributed to its gene coding
      sequence rather than to its transcript levels. These results expand the potential
      of enhancing anthocyanin levels through engineering coding-sequence polymorphisms
      in addition to the transcriptional alterations commonly used. In addition, a
      segregating population obtained from a recombinant genotype revealed that the
      native ANT1, and not AN2, is fully associated with the AFT phenotype and that
      ANT1 alone can generate the characteristic phenotype of anthocyanin accumulation
      in AFT fruits. Our results therefore provide further support to the hypothesis
      that ANT1 is the gene responsible for anthocyanin accumulation in fruits of the
      AFT genotype.

PMID- 21947300
TI  - A placental chorionic villous mesenchymal core cellular origin for infantile
      haemangioma.
AB  - AIMS: To investigate the expression of the placental cell-specific associated
      proteins in infantile haemangioma (IH). METHODS: Immunohistochemical staining was
      used to investigate the expression of human chorionic gonadotrophin (hCG), human
      placental lactogen (hPL), human leucocyte antigen-G (HLA-G), cytokeratin 7 (CK7)
      and smooth muscle actin in paraffin-embedded sections of proliferating and
      involuted IHs. RESULTS: The proteins hCG and hPL were expressed by the
      endothelium but not the pericyte layer of proliferating IH, but these proteins
      were not detected in involuted lesions. There was no expression of CK7 and HLA-G
      in IH. CONCLUSIONS: The expression of hCG and hPL, but not CK7 or HLA-G, by the
      endothelium of proliferating IH supports a placental chorionic villous
      mesenchymal core cellular origin for IH rather than a trophoblast origin.

PMID- 21947301
TI  - EGFR and KRAS quality assurance schemes in pathology: generating normative data
      for molecular predictive marker analysis in targeted therapy.
AB  - INTRODUCTION: The aim of this study was to compare the reproducibility of
      epidermal growth factor receptor (EGFR) immunohistochemistry (IHC), EGFR gene
      amplification analysis, and EGFR and KRAS mutation analysis among different
      laboratories performing routine diagnostic analyses in pathology in The
      Netherlands, and to generate normative data. METHODS: In 2008, IHC, in-situ
      hybridisation (ISH) for EGFR, and mutation analysis for EGFR and KRAS were
      tested. Tissue microarray sections were distributed for IHC and ISH, and tissue
      sections and isolated DNA with known mutations were distributed for mutation
      analysis. In 2009, ISH and mutation analysis were evaluated. False-negative and
      false-positive results were defined as different from the consensus, and
      sensitivity and specificity were estimated. RESULTS: In 2008, eight laboratories
      participated in the IHC ring study. In only 4/17 cases (23%) a consensus score of
      >=75% was reached, indicating that this analysis was not sufficiently reliable to
      be applied in clinical practice. For EGFR ISH, and EGFR and KRAS mutation
      analysis, an interpretable result (success rate) was obtained in >=97% of the
      cases, with mean sensitivity >=96% and specificity >=95%. For small sample
      proficiency testing, a norm was established defining outlier laboratories with
      unsatisfactory performance. CONCLUSIONS: The result of EGFR IHC is not a suitable
      criterion for reliably selecting patients for anti-EGFR treatment. In contrast,
      molecular diagnostic methods for EGFR and KRAS mutation detection and EGFR ISH
      may be reliably performed with high accuracy, allowing treatment decisions for
      lung cancer.

PMID- 21947303
TI  - Evaluating the role for the optical density in the diagnosis of heparin-induced
      thrombocytopenia following cardiac surgery.
AB  - The poor accuracy of the enzyme immune assay (EIA) contributes to the diagnostic
      challenge of heparin-induced thrombocytopenia (HIT) following cardiac surgery. We
      sought to determine if adjusting the threshold optical density (OD) defining a
      positive EIA improves the test's accuracy in subjects with an OD>0.40. We
      retrospectively analysed the results from both EIA and confirmatory serotonin
      release assays (SRAs) in cardiac surgery patients with EIA OD of >0.4. Employing
      the SRA as the standard, we compared the area under the receiver-operating
      characteristic (AUROC) curves of various OD measurements for identifying HIT. We
      examined baseline clinical variables associated with a positive SRA in the
      setting of a positive HIT EIA (OD >0.4). We then used logistic regression to
      identify baseline clinical variables independently associated with a positive SRA
      given a positive EIA. The cohort included 99 subjects with positive EIAs and 35%
      had positive SRAs. An OD>0.40 had moderate utility as a screening test for a
      positive SRA (AUROC: 0.68; 95% CI: 0.55-0.80). Increasing the OD threshold did
      not improve the HIT EIA's screening utility. Clinical variables independently
      associated with a positive SRA if the EIA were positive included female gender,
      absence of diabetes, and use of cardiopulmonary bypass. A relatively modest
      elevation in the OD measurement, when it is already known to be greater than 0.4,
      does not reliably exclude the potential for a positive SRA in this setting.

PMID- 21947302
TI  - Optical coherence tomography shows progressive local nerve fiber loss after disc
      hemorrhages in glaucoma patients.
AB  - BACKGROUND AND AIM: The aim of this work is to investigate whether optic disc
      hemorrhages (ODH) lead to significant loss of nerve fibers at the lesion site
      over time and whether such a loss is reflected by visual field defects
      corresponding to the affected nerve fiber bundle. METHODS: In this retrospective
      study of ten sequential glaucoma patients (ten eyes) with ODH, we used high
      resolution OCT circular scans (Spectralis HRA + OCT, Heidelberg Engineering,
      Heidelberg, Germany) to determine peripapillary retinal nerve fiber layer (RNFL)
      thickness at the time of ODH presentation and at follow-up visit between 3 and 6
      months. Corresponding perimetric data were analyzed for global (mean defect, MD)
      and localized progression of visual field defects. RESULTS: ODH were mostly
      located in the inferior quadrant as determined clinically and from fundus
      photographs. Iterative OCT imaging revealed a significant RNFL reduction in the
      affected quadrant relative to the respective quadrant in the fellow eye (RNFL
      change = -2.25 +/- 2.69 MUm vs. 0.75 +/- 2.78 MUm, p = 0.01) within 120 +/- 43
      days. However, only three cases presented with new/progressive nerve fiber bundle
      defects corresponding to the lesion site within the given follow-up period.
      CONCLUSIONS: ODH lead to a significantly higher RNFL loss at the lesion site
      relative to the overall structural progression in glaucoma patients. However,
      this focal change is not generally reflected by respective nerve fiber bundle
      defects in the time frame investigated.

PMID- 21947304
TI  - Recurrent inflammatory stenosis of the M1 segment: diagnostic and therapeutic
      considerations.

PMID- 21947305
TI  - miRNA-195 sensitizes human hepatocellular carcinoma cells to 5-FU by targeting
      BCL-w.
AB  - The role of microRNA-195 in developing acquired drug resistance in hepatocellular
      carcinoma cells was investigated. Expression profiling of miRNAs revealed a
      limited set of miRNAs with altered expression in drug resistant hepatocellular
      carcinoma cell line BEL-7402/5-FU compared to its parental BEL-7402 cell line.
      Real-time PCR confirmed down-regulation of miRNA-195 in BEL-7402/5-FU cells.
      Overexpression of miRNA-195 sensitized BEL-7402/5-FU cells to anticancer drugs.
      Consistent with these findings, miR-195 antisense oligonucleotide induced drug
      resistance in BEL-7402/5-FU cells. Also, the basal levels of the anti-apoptotic
      protein Bcl-w were high in BEL-7402/5-FU cells and miR-195 overexpression
      repressed Bcl-w protein level and inhibited the luciferase activity of a Bcl-w 3'
      untranslated region-based reporter construct in both BEL-7402/5-FU and BEL-7402
      cells. These results indicate that miR-195 could improve the drug sensitivity at
      least in part by targeting Bcl-w to increase cell apoptosis in hepatocellular
      carcinoma cells.

PMID- 21947306
TI  - A computational investigation on singlet and triplet exciton couplings in acene
      molecular crystals.
AB  - Quantum chemical calculations (DFT, TDDFT and ZINDO/S) of singlet and triplet
      exciton couplings are presented and discussed for some acene derivatives (such as
      anthracene, tetracene, 9,10-di(phenyl)anthracene and 9,10
      bis(phenylethynyl)anthracene). An accurate excited state single molecule
      characterization has been carried out followed by an analysis of the inter
      molecular excitonic interactions, taking place in the crystalline phase. These
      have been correlated to exciton coupling terms obtaining guidelines for the
      choice of molecular materials with large exciton couplings. Such organic systems
      are likely to show multiexciton processes such as singlet fission (SF) and
      triplet-triplet annihilation (TTA) which are useful in energy conversion
      phenomena to be exploited in photonic and optoelectronic devices.

PMID- 21947307
TI  - Silica hollow nanospheres as new nanoscaffold materials to enhance hydrogen
      releasing from ammonia borane.
AB  - Silica hollow nanospheres (SHNS) are used as new nanoscaffold materials to
      confine ammonia borane (NH(3)BH(3), AB) for enhancing the dehydrogenation
      process. Different loading levels of AB in SHNS are considered and AB/4SHNS (with
      AB content of approximately 20 wt%) shows the best result. The onset temperature
      of the dehydrogenation of AB in SHNS is as low as 70  degrees C with the peak
      temperature at 99  degrees C and no other gases such as borazine and ammonia are
      detected. Furthermore, within 60 min at 85  degrees C, 0.53 equivalent of
      hydrogen is released and the activation energy is 97.6 kJ mol(-1). Through FT-IR,
      Raman spectrum and density functional theory (DFT) calculation, it is found that
      nanoconfinement effect combined with SiO-HH-B interaction is essential for the
      enhancement of hydrogen releasing.

PMID- 21947308
TI  - Mosquitocidal and water purification properties of Cynodon dactylon, Aloe vera,
      Hemidesmus indicus and Coleus amboinicus leaf extracts against the mosquito
      vectors.
AB  - Ethanolic extracts of Cynodon dactylon, Aloe vera, Hemidesmus indicus and Coleus
      amboinicus were tested for their toxicity effect on the third-instar larvae of
      Anopheles stephensi, Culex quinquefasciatus and Aedes aegypti. The leaves of C.
      dactylon, A. vera, H. indicus and C. amboinicus were collected from natural
      habitats (forests) in Western Ghats, Tamil Nadu, India. A total of 250 g of
      fresh, mature leaves were rinsed with distilled water and dried in shade. The
      dried leaves were put in Soxhlet apparatus and extract prepared using 100%
      ethanol for 72 h at 30-40 degrees C. Dried residues were obtained from 100 g of
      extract evaporated to dryness in rotary vacuum evaporator. Larvicidal properties
      of ethanolic leaf extracts showed that the extracts are effective as mosquito
      control agents. The larval mortality was observed after 24 h exposure. No
      mortality was observed in the control. The median lethal concentration (LC(50))
      values observed for the larvicidal activities are 0.44%, 0.51%, 0.59% and 0.68%
      for extracts of C. dactylon, A. vera, H. indicus and C. amboinicus, respectively.
      The observed mortality were statistically significant at P < 0.05 level. C.
      dactylon showed the highest mortality rate against the three species of mosquito
      larvae in laboratory and field. The selected plants were shown to exhibit water
      purification properties. Water quality parameters such as turbidity, pH and water
      clarity were analyzed in the water samples (pre-treatment and post-treatment of
      plant extracts) taken from the different breeding sites of mosquitoes. Water
      colour, turbidity and pH were reduced significantly after treatment with C.
      dactylon (13 HU, 31.5 mg/l and 6.9), H. indicus (13.8 HU, 33 mg/l and 7.1), A.
      vera (16 HU, 33.8 mg/l and 7.4) and C. amboinicus (21 HU, 35 mg/l and 7.5)
      extracts. The study proved that the extracts of C. dactylon, A. vera, H. indicus
      and C. amboinicus have both mosquitocidal and water sedimentation properties.

PMID- 21947311
TI  - Cross-platform analysis of longitudinal data in metabolomics.
AB  - Metabolic profiling is considered to be a very promising tool for diagnostic
      purposes, for assessing nutritional status and response to drugs. However, it is
      also evident that human metabolic profiles have a complex nature, influenced by
      many external factors. This, together with the understanding of the difficulty to
      assign people to distinct groups and a general move in clinical science towards
      personalized medicine, raises the interest to explore individual and variable
      metabolic features for each individual separately in longitudinal study design.
      In the current paper we have analyzed a set of metabolic profiles of a selection
      of six urine samples per person from a set of healthy individuals by (1)H NMR and
      reversed-phase UPLC-MS. We have demonstrated that the method for recovery of
      individual metabolic phenotypes can give complementary information to another
      established method for analysis of longitudinal data--multilevel component
      analysis. We also show that individual metabolic signatures can be found not only
      in (1)H NMR data, as has been demonstrated before, but also even more strongly in
      LC-MS data.

PMID- 21947312
TI  - Restricted role of CRF1 receptor for the activity of brainstem catecholaminergic
      neurons in the negative state of morphine withdrawal.
AB  - RATIONALE: Evidence suggests that corticotropin-releasing factor (CRF) system is
      an important mediator in the negative symptoms of opioid withdrawal. OBJECTIVES:
      We used genetically engineered mice lacking functional CRF receptor-1 (CRF1R)
      levels to study the role for CRF/CRF1R pathways in the negative affective states
      of opioid withdrawal. METHODS: Wild-type and CRF1R(-/-) offspring of CRF1R(+/-)
      breeders were identified by PCR analysis of tail DNA and were rendered dependent
      on morphine via intraperitoneal injection of increasing doses of morphine (10-60
      mg/kg). Negative state associated with opioid withdrawal was examined by using
      conditioned place aversion (CPA), TH expression and TH phosphorylation were
      measured in different brain regions involved in addictive behaviours using
      immunohistochemistry. RESULTS: The weight loss in morphine withdrawn CRF1R(-/-)
      animals was significantly (p < 0.05) lower versus wild-type. The aversion for
      environmental cues paired with opioid withdrawal was lower (p < 0.001) in the
      CRF1R-deficient versus wild-type. Using dual immunolabeling for c-Fos, data show
      that naloxone-induced withdrawal increases the number of TH positive neurons
      phosphorylated at Ser40 or Ser31 that coexpress c-Fos in the nucleus of tractus
      solitarius (NTS)-A2 from wild-type and CRF(-/-) deficient mice. By contrast, the
      number of phospho-Ser40 or phospho-Ser31 positive neurons expressing c-Fos was
      lower in the ventrolateral medulla (VLM)-A1 in CRF(-/-)-deficient mice.
      CONCLUSION: Our study demonstrates an increased activity of brainstem
      catecholaminergic neurons after CPA induced by morphine withdrawal suggesting
      that CRF1R is implicated in the activation of A1 neurons and provides evidence
      that this receptor is involved in the body weight loss and in the negative
      aversive effects of morphine withdrawal.

PMID- 21947314
TI  - Interaction between cannabidiol (CBD) and ?(9)-tetrahydrocannabinol (THC):
      influence of administration interval and dose ratio between the cannabinoids.

PMID- 21947313
TI  - Developmental vitamin D deficiency alters MK-801-induced behaviours in adult
      offspring.
AB  - RATIONALE: Developmental vitamin D (DVD) deficiency is a candidate risk factor
      for developing schizophrenia in humans. In rodents DVD deficiency induces subtle
      changes in the way the brain develops. This early developmental insult leads to
      select behavioural changes in the adult, such as an enhanced response to
      amphetamine-induced locomotion in female DVD-deficient rats but not in male DVD
      deficient rats and an enhanced locomotor response to the N-methyl-D: -aspartate
      (NMDA) receptor antagonist, MK-801, in male DVD-deficient rats. However, the
      response to MK-801-induced locomotion in female DVD-deficient rats is unknown.
      Therefore, the aim of the current study was to further examine this behavioural
      finding in male and female rats and assess NMDA receptor density. METHODS: DVD
      deficient Sprague Dawley rats were assessed for locomotion, ataxia, acoustic
      startle response (ASR) and prepulse inhibition (PPI) of the ASR to multiple doses
      of MK-801. The NMDA receptor density in relevant brain regions was assessed in a
      drug-naive cohort. RESULTS: DVD deficiency increased locomotion in response to MK
      801 in both sexes. DVD-deficient rats also showed an enhanced ASR compared with
      control rats, but PPI was normal. Moreover, DVD deficiency decreased NMDA
      receptor density in the caudate putamen of both sexes. CONCLUSIONS: These results
      suggest that a transient prenatal vitamin D deficiency has a long-lasting effect
      on NMDA-mediated signalling in the rodent brain and may be a plausible candidate
      risk factor for schizophrenia and other neuropsychiatric disorders.

PMID- 21947315
TI  - Lithium, but not valproic acid or carbamazepine, suppresses impulsive-like action
      in rats.
AB  - RATIONALE: Higher impulsivity is a pathological symptom in several psychiatric
      disorders, including bipolar disorder, and is a risk factor for suicide.
      OBJECTIVES: Our goal was to determine whether major mood-stabilizing drugs used
      for the treatment of bipolar disorder could suppress impulsive-like action in the
      three-choice serial reaction time task (3-CSRTT). METHODS: Following training for
      the 3-CSRTT, rats were acutely administered lithium chloride (LiCl; 0, 3.2, 10,
      and 32 mg/kg, i.p.), valproic acid (0, 10, 32, and 100 mg/kg, i.p.), or
      carbamazepine (0, 10, 20, and 30 mg/kg, i.p.). To assess the anorexic effects of
      lithium, a simple food consumption test was conducted. RESULTS: LiCl dose
      dependently decreased the number of premature responses, an index of impulsive
      like action. A high dose of LiCl (32 mg/kg) decreased food consumption, but its
      anorexic effects were not correlated with the effects of LiCl on premature
      responses. A moderate dose of LiCl (20 mg/kg) significantly reduced the number of
      premature responses without affecting motivation-related measures in the 3-CSRTT
      or the amount of food consumption. Although carbamazepine prolonged reward
      latency, an index of motivation for food, neither valproic acid nor carbamazepine
      significantly affected premature responses. CONCLUSION: It is likely that lithium
      has a suppressive effect on impulsive action independent of the anorexic effect.
      Lithium may suppress impulsive behavior and thereby decrease the risk of suicide.
      The present results could provide an explanation for the antisuicidal effects of
      lithium and suggest that lithium could be a beneficial treatment for impulsivity
      related disorders.

PMID- 21947316
TI  - Effects of amphetamine on reactivity to emotional stimuli.
AB  - RATIONALE: Most studies of the reinforcing effects of stimulants have focused on
      the drugs' capacity to induce positive mood (i.e., euphoria). However, recent
      findings suggest drugs may also alter emotional reactivity to external stimuli,
      and that this may occur independently of direct effects on mood. OBJECTIVES: We
      aimed to examine effects of D: -amphetamine, a prototypic stimulant, on self
      reported and psychophysiological reactivity to emotional stimuli as well as
      overall subjective mood. We predicted that amphetamine would enhance reactivity
      to pleasant stimuli, particularly, stimuli with social content and that these
      effects would be independent of the drug's direct effects on mood. METHODS: Over
      three sessions, 36 healthy normal adults received placebo, D: -amphetamine 10 and
      20 mg under counterbalanced double-blind conditions. At each session, emotional
      reactivity to standardized positive, neutral, and negative pictures with and
      without social content was measured in self-reports and facial muscles sensitive
      to emotional state. Drug effects on cardiovascular variables and subjective mood
      were also measured. RESULTS: Amphetamine produced euphoria, feelings of drug
      effect, and increased blood pressure. Most notably, amphetamine enhanced self
      reported positive reactions to all pictures and psychophysiological reactions to
      positive pictures. These effects were not significantly related to drug-induced
      mood changes. Contrary to our hypothesis, effects of amphetamine on emotional
      reactivity were not moderated by social content. CONCLUSIONS: This study
      demonstrates a previously unexamined and potentially reinforcing effect of
      stimulant drugs in humans, distinct from more typically measured euphorigenic
      effects, and suggests new areas of research in stimulant abuse risk and
      adaptations occurring during drug dependence.

PMID- 21947317
TI  - Association of the ZFPM2 gene with antipsychotic-induced parkinsonism in
      schizophrenia patients.
AB  - RATIONALE: Antipsychotic-induced parkinsonism (AIP) is a severe adverse affect of
      antipsychotic drug treatment. Recently, our group performed a genome-wide
      association study (GWAS) for AIP severity, and identified several potential AIP
      risk variants. OBJECTIVES: The aim of this study was to validate our original AIP
      GWAS susceptibility variants and to understand their possible function. METHODS:
      We conducted a validation study of 15 single-nucleotide polymorphisms (SNPs) in
      an independent sample of 178 US schizophrenia patients treated for at least a
      month with typical or atypical antipsychotics. Then, a sample of 49 Jewish
      Israeli Parkinson's disease (PD) patients with available neuroimaging ([(123)I]
      FP-CIT-SPECT) data was analyzed, to study association of confirmed AIP SNPs with
      level of dopaminergic deficits in the putamen. RESULTS: Using logistic regression
      and controlling for possible confounders, we found nominal association of the
      intronic SNP, rs12678719, in the Zinc Finger Protein Multitype 2 (ZFPM2) gene
      with AIP (62 affected/116 unaffected), in the whole sample (p = 0.009; P = 5.97 *
      10(-5) in the GWAS), and in the African American sub-sample (N = 111; p = 0.002).
      The same rs12678719-G AIP susceptibility allele was associated with lower levels
      of dopaminergic neuron related ligand binding in the contralateral putamen of PD
      patients (p = 0.026). CONCLUSIONS: Our preliminary findings support association
      of the ZFPM2 SNP, rs12678719, with AIP. At the functional level, this variant is
      associated with deficits in the nigrostriatal pathway in PD patients that may be
      related to latent subclinical deficits among AIP-prone individuals with
      schizophrenia. Further validation studies in additional populations are required.

PMID- 21947318
TI  - Effects of pregabalin on smoking behavior, withdrawal symptoms, and cognitive
      performance in smokers.
AB  - RATIONALE: In preclinical and clinical studies, medications enhancing the GABA
      neurotransmission attenuate nicotine reward. Pregabalin, a GABA analogue,
      presumably interacts with brain glutamate and GABA neurotransmission. The goal of
      this study was to determine pregabalin's effects on smoking behavior, nicotine
      withdrawal, craving for cigarettes, and cognitive performance. METHODS: Twenty
      four smokers participated in an outpatient double-blind, placebo-controlled,
      crossover study. Subjects had a 4-day treatment period with either pregabalin
      (300 mg/day) or placebo and following a washout period were then crossed over for
      4 days to the other treatment. In each treatment period, starting at midnight of
      day 1, participants were asked to stop smoking until the experimental session on
      day 4. During the experimental session measures of ad lib smoking behavior,
      tobacco withdrawal, craving for cigarettes, and cognitive performance were
      obtained. RESULTS: Pregabalin treatment, compared to placebo, did not reduce the
      smoking behavior during the first 3 days of treatment or during ad lib smoking
      period. Pregabalin treatment attenuated some tobacco withdrawal symptoms
      including ratings of anxious, irritable, and frustrated in abstinent smokers.
      Pregabalin treatment also attenuated the subjective ratings of "liking" in
      response to smoking. Under pregabalin treatment, smokers made more errors in a
      sustained attention task. CONCLUSIONS: These findings provide limited support for
      pregabalin as a treatment for nicotine addiction.

PMID- 21947321
TI  - Hypoxia induces CD133 expression in human lung cancer cells by up-regulation of
      OCT3/4 and SOX2.
AB  - CD133 has been recognized as a specific cell surface marker for cancer stem cells
      in various tumors, although its biological functions and transcriptional
      regulation remain unclear. We found that the CD133 expression level was up
      regulated in the lung cancer cell lines N417, H358, and A549, when these cell
      lines were cultured under hypoxic conditions. Among the five promoters (P1-P5) of
      human CD133 gene loci, P1 promoter was most strongly associated with hypoxia
      induced promoter activity of CD133 gene expression. The P1 promoter possesses
      several cis-regulatory elements, including RUNT, GATA, ETS, OCT, SRY, and CREB
      binding sites. A series of deletion and base substitution mutants of the P1
      promoter revealed that OCT- and SRY-binding sites are important for hypoxia
      induced promoter activity. The chromatin immunoprecipitation assay further
      confirmed the direct binding of Octamer biding trans-cription factor 3/4 (OCT4)
      and/or SRY-box containing gene 2 (SOX2) to the P1 promoter region of CD133 gene
      loci. In addition, the enhancement of both OCT4 and SOX2 expression by the alpha
      subunit of hypoxia-inducible factors (HIF1alpha and HIF2alpha) was required for
      hypoxia-induced CD133 expression. Knockdown of OCT4 or SOX2 expression in N417
      cells with stabilized HIF1alpha and/or HIF2alpha abolished CD133P1 activity,
      while ectopic OCT4 or SOX2 expression triggers CD133P1 activity in the absence of
      HIF1alpha or HIF2alpha. Thus, in the hypoxic conditions, OCT4 and SOX2, both of
      which are induced by HIF1alpha/HIF2alpha. promote CD133 expression in the lung
      cancer cells via their direct interaction with the P1 promoter.

PMID- 21947320
TI  - A placebo-controlled study of the modafinil added to risperidone in chronic
      schizophrenia.
AB  - RATIONAL: In recent years, evidence suggests that modafinil may be useful for
      certain symptom domains of schizophrenia, especially for the negative and
      cognitive symptoms. However, the results are not consistent. OBJECTIVE: This
      study was designed to investigate the effect of modafinil added to risperidone in
      patients with chronic schizophrenia in a double blind and randomized clinical
      trial. METHODS: Participants were inpatients males (35) and females (11), ages 20
      49 years at two teaching psychiatric hospital in Iran. All patients were in the
      active phase of the illness and met DSM-IV-TR criteria for schizophrenia.
      Patients were allocated in a random fashion 23 patients to risperidone 6 mg/day
      plus modafinil 200 mg/day and 23 patients to risperidone 6 mg/day plus placebo.
      The principal measure of outcome was the positive and negative syndrome scale
      (PANSS). Patients were assessed by a psychiatrist at baseline and after 2, 4, 6
      and 8 weeks after the start of medication. RESULTS: The modafinil group had
      significantly greater improvement in the negative symptoms as well as PANSS total
      scores over the 8-week trial. Therapy with 200 mg/day of modafinil was well
      tolerated and no clinically important side effects were observed. CONCLUSION: The
      present study indicates modafinil as a potential adjunctive treatment strategy
      for treatment of schizophrenia particularly the negative symptoms. Nevertheless,
      results of larger-controlled trials are needed before recommendation for broad
      clinical application can be made.

PMID- 21947319
TI  - Erythropoietin: a candidate treatment for mood symptoms and memory dysfunction in
      depression.
AB  - OBJECTIVE: Current pharmacological treatments for depression have a significant
      treatment-onset-response delay, an insufficient efficacy for many patients and
      fail to reverse cognitive dysfunction. Erythropoietin (EPO) has neuroprotective
      and neurotrophic actions and improves cognitive function in animal models of
      acute and chronic neurodegenerative conditions and in patients with cognitive
      decline. METHODS: We systematically reviewed the published findings from animal
      and human studies exploring the potential of EPO to treat depression-related
      cognitive dysfunction and depression. RESULTS: We identified five animal studies
      (two in male rats, two in male mice and one in male rats and mice) and seven
      human proof-of-concept studies (five in healthy volunteers and two in depressed
      patients) that investigated the above. All of the reviewed animal studies but one
      and all human studies demonstrated beneficial effects of EPO on hippocampus
      dependent memory and antidepressant-like effects. These effects appear to be
      mediated through direct neurobiological actions of EPO rather than upregulation
      of red cell mass. CONCLUSIONS: The reviewed studies demonstrate beneficial
      effects of EPO on hippocampus-dependent memory function and on depression
      relevant behavior, thus highlighting EPO as a candidate agent for future
      management of cognitive dysfunction and mood symptoms in depression. Larger-scale
      clinical trials of EPO as a treatment for mood and neurocognitive symptoms in
      patients with mood disorder are therefore warranted.

PMID- 21947322
TI  - Role of NF-kappaB-p53 crosstalk in ultraviolet A-induced cell death and G1 arrest
      in human dermal fibroblasts.
AB  - Photoaging is the premature aging of the skin caused by repeated exposure to
      sunlight and is characterized by a depletion of the dermal extracellular matrix.
      This depletion is due to the loss of fibroblast cells and their multiple
      functions. UVA was revealed as a major inducer of photoaging in various clinical
      studies. As UVA photons have long wavelength spectra, UVA penetrates deeper into
      the dermis than UVB and UVC, leading to the induction of cell death, the
      destruction of the dermal extracellular matrix through the induction of matrix
      metalloproteinase expression, and the repression of collagen expression. However,
      the exact effects of UVA on the skin remain a matter of debate. Here, we assess
      cell cycle stage to demonstrate that NF-kappaB-p53 crosstalk induces apoptosis
      and growth arrest in UVA-irradiated human dermal fibroblasts. In addition, UVA
      irradiation led to an increase of NF-kappaB-HDAC1 complexes, which in turn
      repressed cyclin D1 expression in UVA-irradiated human dermal fibroblasts. We
      provide direct evidence that UVA irradiation induces changes in the p53-dependent
      NF-kappaB complex that lead to growth arrest and apoptosis through the repression
      of cyclin D1. These studies uncovered that NF-kappaB-p53 crosstalk is a key
      regulator of UVA-dependent growth arrest and apoptosis.

PMID- 21947323
TI  - Comment on Sen et al.: Posterior wall reconstruction using iliac crest strut
      graft in severely comminuted posterior acetabular wall fracture.

PMID- 21947324
TI  - [Report from the constitutive meeting of the Working Group on Cardiac and
      Transplant Pathology].

PMID- 21947325
TI  - Introgression from cultivated rice influences genetic differentiation of weedy
      rice populations at a local spatial scale.
AB  - Hybridization and introgression can play an important role in genetic
      differentiation and adaptive evolution of plant species. For example, a
      conspecific feral species may frequently acquire new alleles from its coexisting
      crops via introgression. However, little is known about this process. We analyzed
      24 weedy rice (Oryza sativa f. spontanea) populations and their coexisting rice
      cultivars from northern Italy to study their genetic differentiation,
      outcrossing, and introgression based on microsatellite polymorphisms. A total of
      576 maternal plants representing 24 weedy populations were used to estimate their
      genetic differentiation, and 5,395 progeny (seedlings) derived from 299 families
      of 15 selected populations were included to measure outcrossing rates.
      Considerable genetic differentiation (F (st) = 0.26) was detected among weedy
      rice populations, although the differentiation was not associated with the
      spatial pattern of the populations. Private alleles (28%) were identified in most
      populations that exhibited a multiple cluster assignments, indicating stronger
      genetic affinities of some weedy populations. Outcrossing rates were greatly
      variable and positively correlated (R (2) = 0.34, P = 0.02) with the private
      alleles of the corresponding populations. Paternity analysis suggested that ~15%
      of paternal specific alleles, a considerable portion of which was found to be
      crop-specific, were acquired from the introgression of the coexisting rice
      cultivars. Frequent allelic introgression into weedy populations resulting from
      outcrossing with nearby cultivars determines the private alleles of local feral
      populations, possibly leading to their genetic differentiation. Introgression
      from a crop may play an important role in the adaptive evolution of feral
      populations.

PMID- 21947326
TI  - Detection of Candida and Aspergillus species DNA using broad-range real-time PCR
      for fungal endophthalmitis.
AB  - BACKGROUND: The goal of this work is to establish a broad-range real-time
      polymerase chain reaction (PCR) diagnostic system for ocular fungal infection and
      to measure Candida and Aspergillus DNA in the ocular fluids obtained from unknown
      uveitis/endophthalmitis patients. METHODS: After obtaining informed consent,
      intraocular fluids (aqueous humor and vitreous fluid samples) were collected from
      54 patients with idiopathic uveitis or endophthalmitis. Samples were assayed for
      Candida or Aspergillus DNA using broad-range (18S rRNA sequences) quantitative
      real-time PCR. RESULTS: Candida or Aspergillus DNA was detected in seven out of
      54 patient ocular samples (13%). These PCR-positive samples showed significantly
      high copy numbers of Candida or Aspergillus DNA. On the other hand, fungal DNA
      was not detected in any of the other 46 samples collected from these idiopathic
      uveitis or endophthalmitis patients. In the one PCR-negative case, PCR did not
      detect any fungal genome in the sample, even though this patient was clinically
      suspected of having Candida endophthalmitis. Real-time PCR results were negative
      for fungal DNA in the bacterial endophthalmitis patients and in various uveitis
      patients. In addition, fungal DNA was also not detected in patients without
      ocular inflammation (controls). CONCLUSIONS: Analysis of ocular samples by this
      broad-range real-time PCR method can be utilized for rapid diagnosis of patients
      suffering from unknown intraocular disorders such as idiopathic
      uveitis/endophthalmitis.

PMID- 21947327
TI  - Comments on corneal intrastromal tissue modeling with the femtosecond laser.

PMID- 21947328
TI  - Differentiation factors and cytokines in the atherosclerotic plaque micro
      environment as a trigger for macrophage polarisation.
AB  - The phenotype of macrophages in atherosclerotic lesions can vary dramatically,
      from a large lipid laden foam cell to a small inflammatory cell. Classically, the
      concept of macrophage heterogeneity discriminates between two extremes called
      either pro-inflammatory M1 macrophages or anti-inflammatory M2 macrophages.
      Polarisation of plaque macrophages is predominantly determined by the local micro
      environment present in the atherosclerotic lesion and is rather more complex than
      typically described by the M1/M2 paradigm. In this review we will discuss the
      role of various polarising factors in regulating the phenotypical state of plaque
      macrophages. We will focus on two main levels of phenotype regulation, one
      determined by differentiation factors produced in the lesion and the other
      determined by T-cell-derived polarising cytokines. With foam cell formation being
      a key characteristic of macrophages during atherosclerosis initiation and
      progression, these polarisation factors will also be linked to lipid handling of
      macrophages.

PMID- 21947329
TI  - Overexpression of minichromosome maintenance 2 predicts poor prognosis in
      patients with gastric cancer.
AB  - We examined the expression of minichromosome maintenance 2 (MCM2) in gastric
      cancer and adjacent normal tissues and estimated the possible value of MCM2 as a
      novel prognostic marker. Using real-time PCR, western blotting and
      immunohistochemistry, we examined the expression of MCM2 in gastric carcinoma and
      paired normal gastric mucosa. Statistical analysis of the expression of MCM2 mRNA
      and protein in gastric cancer and normal tissues was performed to evaluate the
      relationship between MCM2 expression and clinicopathological characteristics in
      gastric cancer. The expression of MCM2 mRNA and protein in gastric carcinomas was
      significantly higher compared to that in normal gastric mucosa (P=0.04).
      Immunohistochemistry analysis showed that MCM2 expression was significantly up
      regulated in tumor and metastastic lymph node tissues compared with the
      corresponding non-cancerous mucosa (P<0.05). Positive expression of MCM2 was
      significantly associated with patient age, T category and the presence of lymph
      node metastasis (P<0.05). There were no differences between MCM2 expression and
      gender, tumor size, tumor location, M category, International Union Against
      Cancer (UICC) stage, vessel invasion and tumor differentiation. Patients with
      negative tumor MCM2 expression displayed a better survival time than those with
      positive MCM2 expression (P<0.05). Survival analysis showed that positive MCM2
      expression (P<0.05), T stage (P<0.05) and N stage (P<0.05) were independent
      prognostic factors for disease-free survival (DFS) and overall survival (OS). Our
      data suggest that MCM2 could serve as a novel prognostic biomarker in gastric
      carcinoma.

PMID- 21947330
TI  - A conserved regulatory element in the mammalian beta-globin promoters.
AB  - We provide here evidence for a conserved regulatory element for transcription of
      the beta-family globin genes based on a comparative study of 32 genes from 16
      mammals. The element is characterized by the appearance of AA or TT dinucleotides
      in the A + T-rich region located 200-400 bp upstream of the cap sites. G-tracts 3
      5 nucleotides long exist between the A + T-rich region and the conserved
      transcription factor binding sites (GATA-1 site and the CACCC, CCAAT, and ATA
      boxes) apparently dividing the regions. The average periodicity of AA or TT
      dinucleotides in the region from a total of 18 beta-family globin genes from four
      species was approximately 10 bp, suggesting that the DNA in these regions shows
      right-handed superhelicity. The proposed biological function of this element is
      to adjust the spatial positions for the first interaction of the transcription
      factor(s) which can recognize specific DNA sequences in the presence of packed
      chromatin.

PMID- 21947331
TI  - Prestin shows divergent evolution between constant frequency echolocating bats.
AB  - The gene Prestin encodes a motor protein that is thought to confer the high
      frequency sensitivity and selectivity that characterizes the mammalian auditory
      system. Recent research shows that the Prestin gene has undergone a burst of
      positive selection on the ancestral branch of the Old World horseshoe and leaf
      nosed bats (Rhinolophidae and Hipposideridae, respectively), and also on the
      branch leading to echolocating cetaceans. Moreover, these two groups share a
      large number of convergent amino acid sequence replacements. Horseshoe and leaf
      nosed bats exhibit narrowband echolocation, in which the emitted calls are based
      on the second harmonic of a predominantly constant frequency (CF) component, the
      frequency of which is also over-represented in the cochlea. This highly
      specialized form of echolocation has also evolved independently in the
      neotropical Parnell's mustached bat (Pteronotus parnellii). To test whether the
      convergent evolution of CF echolocation between lineages has arisen from common
      changes in the Prestin gene, we sequenced the Prestin coding region (~2,212 bp,
      >99% coverage) in P. parnellii and several related species that use broadband
      echolocation calls. Our reconstructed Prestin gene tree and amino acid tree
      showed that P. parnellii did not group together with Old World horseshoe and leaf
      nosed bats, but rather clustered within its true sister species. Comparisons of
      sequences confirmed that P. parnellii shared most amino acid changes with its
      congeners, and we found no evidence of positive selection in the branch leading
      to the genus of Pteronotus. Our result suggests that the adaptive changes seen in
      Prestin in horseshoe and leaf-nosed bats are not necessary for CF echolocation in
      P. parnellii.

PMID- 21947332
TI  - Recent developments in utilising yoctowells for investigations in nanospace.
AB  - Molecular cavities constructed within rigid monolayers of yoctolitre (1 yL = 10(
      24) L) volume, the so-called yoctowells, are novel surface-engineered systems
      capable of studying the separation, containment and manipulation of individual
      molecules. The properties of the yoctowell can be fine-tuned by the nature of the
      monolayer, or by post-functionalisation leading to amongst others, the
      exploitation of electrostatic effects. The derivatisation of the cavities implies
      they can be used as a means of discriminating between substrates with application
      in molecular sorting of two or more molecular entities in solid devices, or
      become useful as an appropriate model with which to study molecular interactions.
      Of prime importance to all the cases described herein is the use of porphyrins as
      an optical readout (absorption, emission) of the recognition event. In this
      tutorial review, we describe the development of yoctowell chemistry and comment
      on future advances in this technology in light of other literature approaches.

PMID- 21947333
TI  - NMR parameters in alkali, alkaline earth and rare earth fluorides from first
      principle calculations.
AB  - (19)F isotropic chemical shifts for alkali, alkaline earth and rare earth of
      column 3 basic fluorides are measured and the corresponding isotropic chemical
      shieldings are calculated using the GIPAW method. When using the PBE exchange
      correlation functional for the treatment of the cationic localized empty orbitals
      of Ca(2+), Sc(3+) (3d) and La(3+) (4f), a correction is needed to accurately
      calculate (19)F chemical shieldings. We show that the correlation between
      experimental isotropic chemical shifts and calculated isotropic chemical
      shieldings established for the studied compounds allows us to predict (19)F NMR
      spectra of crystalline compounds with a relatively good accuracy. In addition, we
      experimentally determine the quadrupolar parameters of (25)Mg in MgF(2) and
      calculate the electric field gradients of (25)Mg in MgF(2) and (139)La in LaF(3)
      using both PAW and LAPW methods. The orientation of the EFG components in the
      crystallographic frame, provided by DFT calculations, is analysed in terms of
      electron densities. It is shown that consideration of the quadrupolar charge
      deformation is essential for the analysis of slightly distorted environments or
      highly irregular polyhedra.

PMID- 21947335
TI  - Response of the Morus bombycis growing season to temperature and its latitudinal
      pattern in Japan.
AB  - Changes in leaf phenology lengthen the growing season length (GSL, the days
      between leaf budburst and leaf fall) under the global warming. GSL and the leaf
      phenology response to climate change is one of the most important predictors of
      climate change effect on plants. Empirical evidence of climatic effects on GSL
      remains scarce, especially at a regional scale and the latitudinal pattern. This
      study analyzed the datasets of leaf budburst and fall phenology in Morus bombycis
      (Urticales), which were observed by the agency of the Japan Meteorological Agency
      (JMA) from 1953 to 2005 over a wide range of latitudes in Japan (31 to 44 degrees
      N). In the present study, single regression slopes of leaf phenological timing
      and air temperature across Japan were calculated and their spatial patterns using
      general linear models were tested. The results showed that the GSL extension was
      caused mainly by a delay in leaf fall phenology. Relationships between latitude
      and leaf phenological and GSL responses against air temperature were
      significantly negative. The response of leaf phenology and GSL to air temperature
      at lower latitudes was larger than that at higher latitudes. The findings
      indicate that GSL extension should be considered with regards to latitude and
      climate change.

PMID- 21947334
TI  - Mutual independence of 5-HT(2) and alpha1 noradrenergic receptors in mediating
      deficits in sensorimotor gating.
AB  - RATIONALE: Prepulse inhibition (PPI), a preattentional information-filtering
      mechanism, is disrupted by serotonin (5-HT) or norepinephrine (NE) agonists to
      model deficits seen in schizophrenia, but whether this effect occurs through
      interactions between these systems is not known. OBJECTIVES: These studies
      investigated whether PPI/activity changes induced by agonists of one system were
      dependent on neurotransmission within the other. METHODS: Male Sprague-Dawley
      rats received the 5-HT(2) receptor agonist DOI (1-[2,5-dimethoxy-4-iodophenyl]-2
      aminopropane) (0, 0.3 mg/kg), with or without antagonists for alpha1 (prazosin:0,
      0.3, or 1 mg/kg) or beta (timolol:0, 3, or 10 mg/kg) receptors or their
      combination (0 or 0.3 mg/kg prazosin + 3 mg/kg timolol), or the 5-HT(2)
      antagonist ritanserin (0, 2 mg/kg). Separately, the alpha1-adrenergic receptor
      agonist cirazoline (0, 0.68 mg/kg) was given with and without ritanserin (0, 0.5,
      or 2 mg/kg) or the NE antagonists (0 or 0.3 mg/kg prazosin + 3 mg/kg timolol).
      Finally, combinations of subthreshold doses of DOI (0, 0.01, 0.025 mg/kg) and
      cirazoline (0, 0.1, 0.25 mg/kg) were tested for their ability to disrupt PPI, and
      concomitant administration of all three antagonists (0 vs. 0.3 mg/kg prazosin + 3
      mg/kg timolol + 2 mg/kg ritanserin) was assessed for its ability to modify PPI.
      Locomotion was assessed in an additional set of experiments. RESULTS:
      Doses/combinations of prazosin and timolol that reversed cirazoline-induced
      effects did not alter DOI-induced effects, and ritanserin did not affect
      cirazoline at doses that blocked DOI-mediated effects. Concomitant antagonism of
      alpha1 + beta + 5-HT(2) receptors did not modify PPI, nor did combinations of
      subthreshold doses of cirazoline and DOI. CONCLUSIONS: 5-HT(2) receptors and
      alpha1 and beta NE receptors may act through independent mechanisms to modulate
      sensorimotor gating and locomotor activity.

PMID- 21947336
TI  - Surgical correction of ambiguous genitalia in 46-year-old woman.

PMID- 21947337
TI  - Vacuum-assisted breast implant insertion in primary augmentation mammaplasty.

PMID- 21947338
TI  - Reactions of metallodrugs with proteins: selective binding of phosphane-based
      platinum(II) dichlorides to horse heart cytochrome c probed by ESI MS coupled to
      enzymatic cleavage.
AB  - Reactions of cytotoxic platinum drugs with proteins are attracting growing
      attention for their relevant biological implications. We report here on the
      reactions of two cis-diphosphane platinum(II) dichlorides (namely cis
      bis(trimethylphosphane) platinum(II) dichloride and cis-bis(triethylphosphane)
      platinum(II) dichloride) with horse heart cytochrome c (cyt c) monitored through
      advanced ESI MS methods coupled to enzymatic digestion. A remarkable selectivity
      in terms of adduct stoichiometry is highlighted and the specific metal binding
      sites are localised on the protein surface.

PMID- 21947339
TI  - What is the red round ulcer in the cervix?

PMID- 21947340
TI  - The risk of ectopic pregnancy following tubal reconstructive microsurgery and
      assisted reproductive technology procedures.
AB  - PURPOSE: The incidence of ectopic pregnancy (EP) in the general population is 2%,
      whereas the EP rate following assisted reproductive technologies (ART) is between
      2.1 and 11%. EP is also an adverse effect of tubal surgery with incidences up to
      40% depending on the type, location, and severity of tubal disease and the
      surgical procedure. METHODS: This paper looks at the incidence of EP following
      tubal reconstructive microsurgery, analyzes risk factors for EP following own
      1,295 ART cycles and looks on the incidence of EP in 128,314 pregnancies
      following ART according to the presence or absence of tubal infertility using
      data from the German IVF Registry (DIR). RESULTS: In our clinic, the EP rate
      following resterilization was 6.7%. In the presence of acquired tubal disease,
      the EP rate following adhesiolysis, salpingostomy, salpingoneostomy,
      fimbrioplasty, and anastomosis was 7.9%. The EP rate following ART in our clinic
      was 5.6%. Previous abdominal surgeries, microsurgical procedures, hydro
      /sactosalpinges, salpingitis, salpingitis isthmica nodosa, and periadnexal
      adhesions showed a significant positive correlation with EP as outcome. Data of
      DIR demonstrate a significantly increased incidence of EP in the presence of
      tubal pathology. The highest EP rate related to all clinical pregnancies was 4.5%
      (95% CI 3.0-6.0) in smoking women <30 years with tubal pathology following IVF.
      CONCLUSIONS: In the presence of tubal infertility, the incidence of EP following
      ART and tubal microsurgery are approximately comparable with each other and
      higher than in women without tubal infertility. The success of infertility
      surgery depends on a careful selection of appropriate patients.

PMID- 21947341
TI  - Longitudinal field study on bovine Babesia spp. and Anaplasma phagocytophilum
      infections during a grazing season in Belgium.
AB  - Anaplasmosis and babesiosis are major tick-borne diseases with a high economic
      impact but are also a public health concern. Blood samples collected in the
      spring, summer, and autumn of 2010 from 65 cows in seven different farms in
      Belgium were monitored with an indirect immunofluorescence antibody test to
      assess seroprevalence against these pathogens. Seroprevalences to Babesia spp.
      were measured as 10.7%, 20%, and 12.3% in spring, summer, and autumn,
      respectively, whereas seroprevalences to Anaplasma phagocytophilum were 30.8%,
      77%, and 56.9%, respectively. A total of 805 Ixodes ricinus ticks were collected
      at the same time from both cattle (feeding ticks) and grazed pastures (questing
      ticks). The infection level of ticks, assessed by PCR assay, for Babesia spp. DNA
      was 14.6% and 7.9% in feeding and questing ticks, respectively, whereas 21.7% and
      3% of feeding and questing ticks were found be positive for A. phagocytophilum
      cDNA. Fifty-five PCR-positive samples were identified by sequencing as Babesia
      sp. EU1, of which five from feeding ticks were positive for both A.
      phagocytophilum and Babesia sp. EU1. The high density of wild cervids in the
      study area could explain these observations, as deer are considered to be the
      main hosts for adults of I. ricinus. However, the absence of Babesia divergens
      both in feeding and questing ticks is surprising, as the study area is known to
      be endemic for cattle babesiosis. Increasing cervid populations and comorbidity
      could play an import role in the epidemiology of these tick-borne diseases.

PMID- 21947342
TI  - Epidemiological aspects on vector-borne infections in stray and pet dogs from
      Romania and Hungary with focus on Babesia spp.
AB  - Canine arthropod-borne infections are of major interest in small animal practice
      and have been widely investigated in Central and Western Europe. However, only
      limited epidemiological data are available from South-Eastern European countries,
      although diseases including babesiosis or dirofilariosis are widely recognised as
      important canine infections in these countries. A steadily increasing number of
      dogs imported from South-Eastern Europe into Germany require particular attention
      by small animal practitioners. In this study, a total of 216 dogs [29 local
      Romanian pet dogs presented at Salvavet Veterinary Clinic in Bucharest, Romania,
      and 187 imported stray dogs from Romania (n = 109) and Hungary (n = 78) into
      Germany] were screened by molecular biological, serological and haematological
      methods for canine arthropod-borne infections. Eleven different parasitic and
      bacterial vector-borne pathogens-Babesia canis canis, Babesia canis vogeli,
      Babesia gibsoni, Babesia felis-like, Hepatozoon canis, Leishmania spp.,
      Dirofilaria immitis, Dirofilaria repens, Acanthocheilonema reconditum, Anaplasma
      phagocytophilum and Mycoplasma haemocanis-were detected. Fifty-six percent of the
      dogs were positive by direct methods. B. canis canis was the most prevalent
      pathogen in dogs imported to Germany (42.8%) and dogs submitted for clinical
      consultation in Bucharest (44.8%). Our data strongly suggest the introduction of
      an adjusted screening panel in dogs from South-East Europe in view of increasing
      importation of dogs into Germany.

PMID- 21947343
TI  - Analysis of occupational stress in a high fashion clothing factory with upper
      limb biomechanical overload.
AB  - PURPOSE: To study job stress and upper limb biomechanical overload due to
      repetitive and forceful manual activities in a factory producing high fashion
      clothing. METHODS: A total of 518 workers (433 women and 85 men) were
      investigated to determine anxiety, occupational stress (using the Italian version
      of the Karasek Job Content Questionnaire) and perception of symptoms (using the
      Italian version of the Somatization scale of Symptom Checklist SCL-90).
      Biomechanical overload was analyzed using the OCRA Check list. RESULTS:
      Biomechanical assessment did not reveal high-risk jobs, except for cutting.
      Although the perception of anxiety and job insecurity was within the normal
      range, all the workers showed a high level of job strain (correlated with the
      perception of symptoms) due to very low decision latitude. CONCLUSION:
      Occupational stress resulted partially in line with biomechanical risk factors;
      however, the perception of low decision latitude seems to play a major role in
      determining job strain. Interactions between physical and psychological factors
      cannot be demonstrated. Anyway, simultaneous long-term monitoring of occupational
      stress features and biomechanical overload could guide workplace interventions
      aimed at reducing the risk of adverse health effects.

PMID- 21947344
TI  - Selective sweep at the Rpv3 locus during grapevine breeding for downy mildew
      resistance.
AB  - The Rpv3 locus is a major determinant of downy mildew resistance in grapevine
      (Vitis spp.). A selective sweep at this locus was revealed by the DNA genotyping
      of 580 grapevines, which include a highly diverse set of 265 European varieties
      that predated the spread of North American mildews, 82 accessions of wild
      species, and 233 registered breeding lines with North American ancestry produced
      in the past 150 years. Artificial hybridisation and subsequent phenotypic
      selection favoured a few Rpv3 haplotypes that were introgressed from wild vines
      and retained in released varieties. Seven conserved haplotypes in five descent
      groups of resistant varieties were traced back to their founders: (1) 'Munson', a
      cross between two of Hermann Jaeger's selections of V. rupestris and V.
      lincecumii made in the early 1880s in Missouri, (2) V. rupestris 'Ganzin', first
      utilised for breeding in 1879 by Victor Ganzin in France, (3) 'Noah', selected in
      1869 from intermingled accessions of V. riparia and V. labrusca by Otto
      Wasserzieher in Illinois, (4) 'Bayard', a V. rupestris * V. labrusca offspring
      generated in 1882 by George Couderc in France, and (5) a wild form closely
      related to V. rupestris accessions in the Midwestern United States and
      introgressed into 'Seibel 4614' in the 1880s by Albert Seibel in France.
      Persistence of these Rpv3 haplotypes across many of the varieties generated by
      human intervention indicates that a handful of vines with prominent resistance
      have laid the foundation for modern grape breeding. A rampant hot spot of NB-LRR
      genes at the Rpv3 locus has provided a distinctive advantage for the adaptation
      of native North American grapevines to withstand downy mildew. The coexistence of
      multiple resistance alleles or paralogues in the same chromosomal region but in
      different haplotypes counteracts efforts to pyramidise them in a diploid
      individual via conventional breeding.

PMID- 21947345
TI  - Molecular phylogeny of the genus Asparagus (Asparagaceae) explains interspecific
      crossability between the garden asparagus (A. officinalis) and other Asparagus
      species.
AB  - The genus Asparagus comprises approximately 200 species, some of which are
      commercially cultivated, such as the garden asparagus (A. officinalis). Many
      Asparagus species, including A. officinalis, are dioecious and have been grouped
      into a subgenus distinct from that of hermaphroditic species. Although many
      interspecific crossings have been attempted to introduce useful traits into A.
      officinalis, only some of the dioecious species were found to be cross-compatible
      with A. officinalis. Here, molecular phylogenetic analyses were conducted to
      determine whether interspecific crossability is proportional to the genetic
      distance between the crossing pairs and to further clarify the evolutionary
      history of the Asparagus genus. A clade with all cross-compatible species and no
      cross-incompatible species was recovered in the phylogenetic tree based on
      analyses of non-coding cpDNA regions. In addition, a sex-linked marker developed
      for A. officinalis amplified a male-specific region in all cross-compatible
      species. The phylogenetic analyses also provided some insights about the
      evolutionary history of Asparagus; for example, by indicating that the genus had
      its origin in southern Africa, subsequently spreading throughout the old world
      through intensive speciation and dispersal. The results also suggest that
      dioecious species were derived from a single evolutionary transition from
      hermaphroditism in Asparagus. These findings not only contribute towards the
      understanding of the evolutionary history of the genus but may also facilitate
      future interspecific hybridization programs involving Asparagus species.

PMID- 21947346
TI  - Tumor suppressor p53 down-regulates expression of human leukocyte marker CD43 in
      non-hematopoietic tumor cells.
AB  - CD43 (leukosialin, sialophorin), a cell surface protein on most hematopoietic
      cells, is an important regulator of immune cell function and is involved in
      regulation of cell adhesion and proliferation. Aberrant expression of CD43 is a
      common event observed in human tumors of non-hematopoietic origin suggesting a
      role in tumor development. We have previously shown that overexpression of CD43
      causes activation of the ARF-p53 tumor-suppressor pathway and results in cell
      death. In a non-functional ARF-p53 background, the cells overexpressing CD43
      display an increased cell growth rate due to higher survival. Here we show that
      p53 specifically downregulates the expression of CD43 at the protein and mRNA
      level. Transactivating properties of p53 are necessary to affect the expression
      of exogenous CD43. The downregulation of CD43 mRNA is caused by p53-dependent
      transrepression, at least in part, via a histone deacetylation mechanism. These
      studies establish that under certain conditions there exists a negative feedback
      loop between p53 and CD43: CD43-dependent signaling activates p53, which in turn
      downregulates the expression of CD43.

PMID- 21947347
TI  - Association of the MDR1 3435 polymorphism in patients with refractory rheumatoid
      arthritis in a Chinese population.
AB  - To evaluate whether the multidrug resistance gene 1 (MDR1) exon 26 polymorphisms
      are associated with the refractory rheumatoid arthritis (RRA). The study was
      carried out on two hundred and twenty-three patients with RA treated and one
      hundred and three normal controls. The RA treated were divided into two groups
      according the response to disease-modifying antirheumatic drugs (DMARDs). There
      were 108 patients in the effective group and 115 patients in the ineffective
      group. Genotypes of the C3435T polymorphism were determined by polymerase chain
      reaction followed by restriction digestion (PCR-RFLP). There were significant
      differences in the genotype frequency and allele frequency among three groups.
      Compared to responders and controls, the nonresponders carried more CC genotype
      (chi(2) = 5.306, P = 0.021; chi(2) = 7.810, P = 0.005) and more C allele (chi(2)
      = 6.601, P = 0.010; chi(2) = 12.172, P = 0.000). But, there were no statistically
      significant differences in genotype nor allele frequency between RA and healthy
      controls. The results from our study suggest that the C3435T MDR1 gene
      polymorphism may not be related with the RA susceptibility, but may influence the
      efficacy of RA therapy with DMARDs, and the 3435CC genotype may be related with
      RRA.

PMID- 21947348
TI  - Herpes zoster infection, vaccination and immunocompromised rheumatology patients.
AB  - Varicella is a self-limiting and relatively mild disease of childhood, although
      it is frequently more severe and complicated among the immunocompromised
      rheumatology patients on immunomodulator therapies. In addition, future
      reactivation of the dormant virus in dorsal root ganglia may cause herpes zoster
      infection, which can be very debilitating. In this manuscript, we discuss the
      nature of this infection along with its potential vaccine especially among
      rheumatology patients.

PMID- 21947349
TI  - Dermatomyositis complicated with a soft tissue sarcoma.

PMID- 21947351
TI  - Evolutionary conservation of the lipopolysaccharide binding site of beta2
      glycoprotein I.
AB  - beta2-Glycoprotein I (beta2GPI) is a highly abundant plasma protein and the major
      antigen for autoantibodies in the antiphospholipid syndrome. Recently, we have
      described a novel function of beta2GPI as scavenger of lipopolysaccharide (LPS).
      With this in mind we investigated the conservation of beta2GPI in vertebrates and
      set out to identify the binding site of LPS within beta2GPI. The genome sequences
      of 42 species were surveyed. Surface plasmon resonance (SPR) was performed with
      peptides to characterise the binding site of beta2GPI for LPS. beta2GPI could be
      identified in most tested vertebrates with a high overall amino acid homology of
      80% or more in mammals. SPR revealed that a synthesised peptide (LAFWKTDA) from
      domain V of beta2GPI was able to compete for binding of beta2GPI to LPS. The
      AFWKTDA sequence was completely conserved in all mammals. The peptide containing
      the LPS binding site attenuated the inhibition by beta2GPI in a cellular model of
      LPS-induced tissue factor expression. Other important sites, such as the binding
      site for anionic phospholipids and the antiphospholipid antibody binding epitope,
      were also preserved. beta2GPI is highly conserved across the animal kingdom,
      which suggests that the function of beta2GPI may be more important than
      anticipated.

PMID- 21947350
TI  - Compliance with treatment of rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic, progressive, debilitating disease that
      demands continuous therapy with multiple medications. Noncompliance with disease
      modifying drugs may cause disease flares, preventable functional impairment,
      unnecessary treatment changes, and loss of health care resources. The aim of the
      current study was to explore self-reported compliance with treatment and the
      factors contributing to this compliance using a representative sample of an RA
      patient population in Estonia. Two thousand patients diagnosed with RA were
      randomly selected from the Estonian Health Insurance Fund database. The eligible
      response rate of the study was 60%. Using prestructured questionnaires, the
      following information about the disease and treatment was evaluated: self
      reported compliance with treatment, reasons for noncompliance, disease history,
      sociodemographic variables, health care utilization, and satisfaction with health
      care providers. The self-reported compliance rate was 80.3%, reflecting the
      percentage of patients who reported that they always took their medications
      exactly as described. The most often reported reasons for noncompliance were side
      effects and fear of side effects. Compliance was found to be the lowest in a
      group of younger and active patients with higher income. Higher frequency of
      visits to the rheumatologist, satisfaction with health care providers, and
      sufficient information about RA treatment correlated with better compliance.

PMID- 21947352
TI  - Predictors of chronic valvular disease in patients with rheumatic carditis.
AB  - This study investigated the predictors of chronic valvular disease in children
      with rheumatic carditis. The short- to mid-term follow-up records of 88 patients
      (mean age, 10.68 +/- 2.5 years) with chronic rheumatic heart disease were
      reviewed. The mean follow-up period was 2.95 +/- 1.4 years. Valvular involvement
      completely improved for 24 of the patients (27%) during the follow-up period. The
      multivariate logistic regression analysis found initial left ventricular dilation
      to be a significant independent risk factor associated with the persistence of
      either valvular involvement or mitral regurgitation. Furthermore, persistence of
      mitral regurgitation was found to be strongly correlated with cardiac murmur at
      admission. No significant correlation was detected between age, gender, severity
      of valvular involvements at initial evaluation, and chronic valvular disease. The
      majority of patients with rheumatic carditis had normal left ventricular systolic
      function. However, a significant proportion of patients had left ventricular
      dilation, reported in the medical literature to be associated with the severity
      of valve involvement. This study found no relation between initial severity of
      valve involvements and chronic valvular disease. For this reason, increased left
      ventricular end-diastolic diameter may be secondary to myocardial involvement
      independent of valvular regurgitation. The findings in this study also suggest
      that subclinic carditis had a better outcome than clinically evident carditis.

PMID- 21947353
TI  - Critical Ebstein anomaly in a fetus successfully managed by elective preterm
      delivery and surgical intervention without delay after birth.
AB  - This report describes a case of Ebstein anomaly in a fetus with cardiomegaly,
      severe tricuspid regurgitation, pulmonary regurgitation, and retrograde ductal
      flow that showed a marked increase in the size of the right atrium with advancing
      gestational age. Elective preterm delivery was performed at 35 weeks gestation.
      The prostaglandin E1 infusion resulted in more pronounced systemic hypotension
      and acidosis secondary to circular shunt across the patent ductus arteriosus as
      well as pulmonary regurgitation and tricuspid regurgitation. Emergency surgical
      intervention consisting of main pulmonary artery ligation, ductus arteriosus
      ligation, central shunt creation, and plication of the right atrium without
      cardiopulmonary bypass was performed 4 h after birth. At the age of 16 days, the
      Starnes procedure was performed. The infant's postoperative course was
      uneventful. A fetus that has Ebstein anomaly associated with pulmonary
      regurgitation is at risk for circular shunt across the patent ductus arteriosus
      after delivery. Planned delivery and surgical intervention without delay after
      birth are useful for the treatment of such cases.

PMID- 21947354
TI  - Corticosteroid dependent and independent effects of a cannabinoid agonist on core
      temperature, motor activity, and prepulse inhibition of the acoustic startle
      reflex in Wistar rats.
AB  - RATIONALE: There are inconsistent reports on the effects of cannabinoid agonists
      on prepulse inhibition of the startle reflex (PPI) with increases, decreases, and
      no effects. It has been hypothesized that the conflicting observations may be as
      a result of modulation of the effects of cannabinoid agonists by the regulation
      of corticosteroid release. OBJECTIVE: The purpose of the present study was to
      determine the effects of CP55940, a cannabinoid agonist, and metyrapone, a
      corticosteroid synthesis inhibitor on core temperature, motor activity, the
      startle reflex, and PPI. METHODS: Startle responses were measured in 64 male
      Wistar rats while varying startling stimulus intensities, analogous to dose
      response curves. A stimulus potency measure (ES(50)) and a response measure, the
      maximal achievable response (R (MAX)) were derived from the stimulus-response
      curves. RESULTS: CP55940 reduced core temperature and motor activity; these
      effects were potentiated by metyrapone. CP55940 increased R (MAX) of startle in
      the absence of a prepulse by a corticosteroid-dependent mechanism but decreased
      it when metyrapone was administered before CP55940, a corticosteroid-independent
      mechanism. The inverse of stimulus potency (ES(50)) was not affected by either
      drug alone but was increased by the combined drugs. CP55940 increased the
      prepulse motor gating effects and decreased the prepulse sensory gating effects
      of the same prepulses but only when given after metyrapone. CONCLUSIONS: The most
      parsimonious interpretation of these effects is that CP55940 has some effects
      through corticosteroid-dependent actions and opposite effects by corticosteroid
      independent actions. These two putative sites of actions affect stimulus gating
      opposite to their effects on response gating.

PMID- 21947355
TI  - Effects of caffeine on persistence and reinstatement of nicotine-seeking behavior
      in rats: interaction with nicotine-associated cues.
AB  - RATIONALE: Caffeine and nicotine are the most commonly co-used psychostimulants.
      However, it is still unclear whether caffeine exposure enhances nicotine-seeking
      behavior. OBJECTIVE: The present study examined the effects of caffeine on
      nicotine-seeking in rats trained to self-administer nicotine with and without
      presession administration of caffeine. METHODS: Male Sprague-Dawley rats were
      trained to intravenously self-administer nicotine (0.03 mg/kg/infusion, freebase)
      on a fixed ratio 5 schedule of reinforcement and associate a stimulus cue with
      each nicotine administration. Five minutes before the sessions, the rats received
      an intraperitoneal administration of caffeine (5 mg/kg). Extinction tests were
      conducted under four conditions: presession caffeine administration, response
      contingent presentation of nicotine cues, neither condition, or both conditions.
      Reinstatement tests were conducted after responding was extinguished by
      withholding presession caffeine, nicotine, and its cues. A separate group of rats
      trained without presession caffeine exposure was also subjected to the
      reinstatement tests. RESULTS: In the rats trained with presession caffeine
      exposure, continued caffeine administration sustained nicotine-seeking responses
      and interacted with nicotine cues to significantly delay the extinction of
      nicotine-seeking behavior. Readministration of caffeine after extinction
      effectively reinstated nicotine-seeking behavior. In caffeine-naive rats,
      caffeine administration did not reinstate extinguished nicotine-seeking behavior
      but significantly potentiated the cue-induced reinstatement of nicotine-seeking.
      CONCLUSION: These data demonstrate that caffeine administration sustained and
      reinstated nicotine-seeking behavior, possibly via its acquired discriminative
      stimulus properties predictive of nicotine availability. These findings suggest
      that smokers who attempt to quit may benefit from stopping caffeine consumption.

PMID- 21947357
TI  - Plasma effects in semiconducting nanowire growth.
AB  - Three case studies are presented to show low-temperature plasma-specific effects
      in the solution of (i) effective control of nucleation and growth; (ii)
      environmental friendliness; and (iii) energy efficiency critical issues in
      semiconducting nanowire growth. The first case (related to (i) and (iii)) shows
      that in catalytic growth of Si nanowires, plasma-specific effects lead to a
      substantial increase in growth rates, decrease of the minimum nanowire thickness,
      and much faster nanowire nucleation at the same growth temperatures. For
      nucleation and growth of nanowires of the same thickness, much lower temperatures
      are required. In the second example (related to (ii)), we produce Si nanowire
      networks with controllable nanowire thickness, length, and area density without
      any catalyst or external supply of Si building material. This case is an
      environmentally-friendly alternative to the commonly used Si microfabrication
      based on a highly-toxic silane precursor gas. The third example is related to
      (iii) and demonstrates that ZnO nanowires can be synthesized in plasma-enhanced
      CVD at significantly lower process temperatures than in similar neutral gas-based
      processes and without compromising structural quality and performance of the
      nanowires. Our results are relevant to the development of next-generation
      nanoelectronic, optoelectronic, energy conversion and sensing devices based on
      semiconducting nanowires.

PMID- 21947356
TI  - Effect of lamotrigine and carbamazepine on corticotropin-releasing factor
      associated serotonergic transmission in rat dorsal raphe nucleus.
AB  - Corticotropin-releasing factor (CRF) and serotonin are important transmitters of
      the pathophysiology of mood disorder. To clarify the mechanisms of action of
      lamotrigine (LTG) and carbamazepine (CBZ), we determined their effects on
      serotonin release associated with CRF in rat dorsal raphe nucleus (DRN) and
      median prefrontal cortex (mPFC) using dual-probe microdialysis. Neither perfusion
      with CRF1 nor CRF2 antagonists into DRN-affected serotonin release in DRN and
      mPFC. Perfusion of 10 MUM CRF into DRN increased serotonin release in both
      regions, whereas 0.1 MUM CRF decreased and had no effect on serotonin release in
      DRN and mPFC, respectively. Pre-perfusion with CRF1 antagonist into DRN inhibited
      0.1 MUM CRF-induced serotonin reduction, whereas pre-perfusion with CRF2
      antagonist in DRN inhibited 10 MUM CRF-induced serotonin elevation, without
      affecting 0.1 MUM CRF-induced serotonin reduction. LTG perfusion concentration
      dependently decreased serotonin releases in DRN and mPFC. Therapeutic and
      supratherapeutic concentrations of CBZ increased and decreased serotonin releases
      in both regions, respectively. Pre-perfusion with sub-therapeutic concentration
      LTG inhibited CRF1-induced serotonin reduction without affecting CRF2-induced
      serotonin release, whereas pre-perfusion with therapeutic concentration of LTG
      inhibited both CRF1- and CRF2-actions. In contrast, both therapeutic and
      supratherapeutic concentrations of CBZ inhibited CRF2-induced serotonin release
      without affecting CRF1-induced serotonin reduction. Neither LTG nor CBZ affected
      the CRF-induced cAMP production in cells over-expressing CRF1 and CRF2 receptors.
      This study demonstrated that inhibition of CRF2-receptor-mediated serotonergic
      transmission is a mechanism shared by LTG and CBZ, two clinically related
      compounds, whereas LTG but not CBZ inhibits CRF1-receptor-mediated serotonergic
      transmission. Therefore, these mechanisms may contribute to the clinical actions
      of these agents.

PMID- 21947358
TI  - Optical chemosensors and reagents to detect explosives.
AB  - This critical review is focused on examples reported from 1947 to 2010 related to
      the design of chromo-fluorogenic chemosensors and reagents for explosives (141
      references).

PMID- 21947359
TI  - Collisional relaxation of MnH (X7Sigma+) in a magnetic field: effect of the
      nuclear spin of Mn.
AB  - In the present study we investigate the role played by the hyperfine structure of
      manganese in the cooling and magnetic trapping of MnH((7)Sigma(+)). The effect of
      the hyperfine structure of Mn on the relaxation of the magnetically trappable
      maximally stretched low-field seeking state of MnH((7)Sigma(+)) in collisions
      with (3)He is deduced from comparison between the results of the present approach
      and our previous nuclear spin free calculations. We show that our previous
      results are unchanged at the temperature of the buffer gas cooling experiment but
      find a new resonance at very low collision energy. The role played by the
      different contributions to the hyperfine diatomic Hamiltonian considered in this
      work as well as the effect of an applied magnetic field on this resonance are
      also analyzed.

PMID- 21947360
TI  - Endometrial adenocarcinoma with osteoclastic giant cells in stroma: a case report
      and review of literature.
AB  - It is rare to find osteoclastic giant cells (OGCs) as a stromal reaction in
      uterine adenocarcinoma of endometrium. Here, we report a case of a 60-year-old
      female diagnosed with adenocarcinoma of endometrium. Total hysterectomy with
      bilateral salpingo-oopherectomy and removal of pelvic lymphnodes was performed.
      Histologically, the tumour showed adenocarcinoma of the endometrium with mucin
      secretion. The stroma showed some plump reactive pleomorphic cells, resembling
      stromal cells, infiltrated uniformly with OGCs and mononuclear cells (MNCs). The
      epithelial cells of adenocarcinoma stained positive for cytokeratin (CK 7) (CAM
      5.2). The osteoclastic giant cells and mononuclear cells stained positive with
      CD68 and negative with cytokeratin and vimentin. We conclude that the
      osteoclastic giant cells originated from reactive histiocytes/monocytes as a
      stromal reaction to malignancy.

PMID- 21947361
TI  - Protective effects of IL-4 on Bacillus Calmette-Guerin and lipopolysaccharide
      induced immunological liver injury in mice.
AB  - OBJECTIVE: Mice injected with Bacillus Calmette-Guerin (BCG) were challenged with
      lipopolysaccharide (LPS) to induce inflammatory liver injury. This study was
      performed to explore the protective effects of interleukin (IL)-4 against liver
      injury induced by BCG and LPS in mice. MATERIALS AND METHODS: Mice injected with
      BCG (125 mg/kg) were challenged with LPS (10 MUg/kg) to induce the model of
      inflammatory liver injury. Half an hour after injection of LPS, mice were
      subcutaneously administered rmIL-4 at 5 and 0.5 MUg/kg, respectively. Liver
      injury was evaluated by serum transaminase assay and H & E staining. Liver
      cytokine concentrations were determined by enzyme-linked immunosorbent assay, and
      intrahepatic cytokine and iNOS mRNA levels by reverse transcriptase polymerase
      chain reaction. Intrahepatic apoptosis was evaluated by terminal deoxynucleotidyl
      transferase mediated nick end labeling. NF-kappaB p65 and ERK signal pathway was
      detected by Western-blotting. NF-kappaB signal pathway was also detected by
      electrophoretic mobility shift assay. RESULTS: IL-4 reduced the serum ALT, AST
      and LDH, alleviated the inflammatory cells infiltration, down regulated the
      expression of TNF-alpha, IL-1beta, IFN-gamma, IL-6 and iNOS mRNA in liver, and
      alleviated hepatic glutathione depletion (GSH). In addition, IL-4 displayed
      inhibition of extracellular signal-regulated kinase phosphorylation and NF-kappaB
      activation. CONCLUSION: IL-4 may protect mice against BCG/LPS-induced immune
      liver injury, besides ERK and NF-kappaB signal pathways were involved in the
      effects.

PMID- 21947362
TI  - Persistent dyslipidemia in Austrian patients treated with statins for primary and
      secondary prevention of atherosclerotic events - Results of the DYSlipidemia
      International Study (DYSIS).
AB  - BACKGROUND: Statins reduce cardiovascular events by about one third; thus two out
      of three events occurring without any lipid lowering treatment still might happen
      under statin treatment. One reason may be that lipid targets are not met. The
      DYSlipidemia International Study (DYSIS) was performed to determine the
      prevalence of persistent dyslipidemia despite statin treatment in Austria.
      PATIENTS AND METHODS: Between April 2008 and February 2009, 910 outpatients on
      current statin treatment and aged >= 45 years were recruited by general
      practitioners, cardiologists, endocrinologists, and internists. A clinical
      examination was performed and lipid values were obtained under stable statin
      therapy. The ESC guidelines version 2007 served as criteria to judge the
      attainment of treatment targets for LDL cholesterol and to reach normal HDL
      cholesterol and triglyceride levels. In 765 patients a full lipid profile
      including fasting cholesterol, fasting triglycerides, HDL-cholesterol, and LDL
      cholesterol could be obtained. RESULTS: Of our patients, 74.5% had at least one
      lipid parameter not at target. Specifically, 52.3% did not reach the LDL
      cholesterol target as according to the ESC guidelines 2007 - and 56.4% as
      according to the Austrian lipid consensus 2010 -, 59.1% had above-target total
      cholesterol levels and 42.5% had elevated triglyceride levels. In 23% of the
      patients the HDL cholesterol was below levels associated with increased
      cardiovascular risk. In patients with only one single value beyond normal or
      targeted level, LDL cholesterol had a prevalence of 24.3%, HDL of 11.9% and
      triglycerides of 24.5%. In 8.4% of patients, all 3 parameters, LDL-cholesterol,
      HDL-cholesterol and triglycerides, were out of range. CONCLUSIONS: About three
      quarters of the Austrian patients under chronic statin therapy in routine
      clinical practice failed to meet lipid values as set by international and
      Austrian guidelines. There is an urgent need for more effective strategies to
      better control dyslipidemia in statin treated patients with the aim of further
      reducing cardiovascular events.

PMID- 21947363
TI  - Long lasting remission by rituximab in a patient with primary cold agglutinin
      autoimmune haemolytic anaemia.
AB  - A 76-year-old female patient with cold agglutinin autoimmune haemolytic anaemia
      (CAHA) is presented. The haemolysis worsened during infection. Earlier, the
      patient underwent an unsuccessful treatment with steroids, chlorambucil , folic
      acid and heated erythrocyte transfusion. We treated her with monoclonal anti-CD20
      antibody Rituximab (RTX) weekly for four consecutive weeks. After three cycles,
      the signs of haemolysis slowly disappeared and haemoglobin completely normalized.
      We continued with the maintenance treatment with RTX every third month for 2
      years. The patient is in complete remission. This case report emphasizes the
      importance of the use of RTX as a therapy for immune cytopenia. Patients with
      CAHA usually fail to respond to standard treatment. Since CAHA is a very rare
      condition, only some case reports and 2 studies reported on the positive effects
      of RTX. Although expensive, RTX has many advantages, such as quick and long-term
      efficiency and only a few side effects.

PMID- 21947364
TI  - Identification and validation of novel adipokines released from primary human
      adipocytes.
AB  - Adipose tissue is a major endocrine organ, releasing signaling and mediator
      proteins, termed adipokines, via which adipose tissue communicates with other
      organs. Expansion of adipose tissue in obesity alters adipokine secretion, which
      may contribute to the development of metabolic diseases. Although recent
      profiling studies have identified numerous adipokines, the amount of overlap from
      these studies indicates that the adipokinome is still incompletely characterized.
      Therefore, we conducted a complementary protein profiling on concentrated
      conditioned medium derived from primary human adipocytes. SDS-PAGE/liquid
      chromatography-electrospray ionization tandem MS and two-dimensional SDS
      PAGE/matrix-assisted laser desorption ionization/time of flight MS identified 347
      proteins, 263 of which were predicted to be secreted. Fourty-four proteins were
      identified as novel adipokines. Furthermore, we validated the regulation and
      release of selected adipokines in primary human adipocytes and in serum and
      adipose tissue biopsies from morbidly obese patients and normal-weight controls.
      Validation experiments conducted for complement factor H, alphaB-crystallin,
      cartilage intermediate-layer protein, and heme oxygenase-1 show that the release
      and expression of these factors in adipocytes is regulated by differentiation and
      stimuli, which affect insulin sensitivity, as well as by obesity. Heme oxygenase
      1 especially reveals to be a novel adipokine of interest. In vivo, circulating
      levels and adipose tissue expression of heme oxygenase-1 are significantly
      increased in obese subjects compared with lean controls. Collectively, our
      profiling study of the human adipokinome expands the list of adipokines and
      further highlights the pivotal role of adipokines in the regulation of multiple
      biological processes within adipose tissue and their potential dysregulation in
      obesity.

PMID- 21947366
TI  - Integrating ecological knowledge, public perception and urgency of action into
      invasive species management.
AB  - Recently Prevot-Julliard and colleagues presented a concept paper on biological
      conservation strategies using exotic species as a case study. They emphasized the
      difficulty of integrating conservation into a broad picture that accounts for
      public perception as well as scientific knowledge. We support this general call
      for better integration of society in conservation research, but we believe that
      the original framework might misguide conservation practices if wrongly
      interpreted. Our objective is to complement their paper and correct a few
      misleading points, by showing that (1) for regions of high endemicity
      "reservation" may be the best conservation practice, and does not prevent public
      participation, (2) aiming for broad societal agreement is valuable, but in some
      cases risky, and always complex, and (3) calling a harmful invasive species
      harmful shouldn't be an issue. The Australian context provides us with many cases
      of the labeling of exotic species as harmful or not, using inputs from
      scientists, industry, and the public. Integration of social and scientific points
      of view can only improve conservation on the ground if it allows managers to use
      the ecological, economic and social impacts of exotic species to prioritize
      conservation actions in an operative way.

PMID- 21947365
TI  - Discovery of lung cancer biomarkers by profiling the plasma proteome with
      monoclonal antibody libraries.
AB  - A challenge in the treatment of lung cancer is the lack of early diagnostics.
      Here, we describe the application of monoclonal antibody proteomics for discovery
      of a panel of biomarkers for early detection (stage I) of non-small cell lung
      cancer (NSCLC). We produced large monoclonal antibody libraries directed against
      the natural form of protein antigens present in the plasma of NSCLC patients.
      Plasma biomarkers associated with the presence of lung cancer were detected via
      high throughput ELISA. Differential profiling of plasma proteomes of four
      clinical cohorts, totaling 301 patients with lung cancer and 235 healthy
      controls, identified 13 lung cancer-associated (p < 0.05) monoclonal antibodies.
      The monoclonal antibodies recognize five different cognate proteins identified
      using immunoprecipitation followed by mass spectrometry. Four of the five
      antigens were present in non-small cell lung cancer cells in situ. The approach
      is capable of generating independent antibodies against different epitopes of the
      same proteins, allowing fast translation to multiplexed sandwich assays. Based on
      these results, we have verified in two independent clinical collections a panel
      of five biomarkers for classifying patient disease status with a diagnostics
      performance of 77% sensitivity and 87% specificity. Combining CYFRA, an
      established cancer marker, with the panel resulted in a performance of 83%
      sensitivity at 95% specificity for stage I NSCLC.

PMID- 21947367
TI  - Taxonomic and functional responses to fire and post-fire management of a
      Mediterranean hymenoptera community.
AB  - Fire is one of the commonest disturbances worldwide, transforming habitat
      structure and affecting ecosystem functioning. Understanding how species respond
      to such environmental disturbances is a major conservation goal that should be
      monitored using functionally and taxonomically diverse groups such as
      Hymenoptera. In this respect, we have analyzed the taxonomic and functional
      response to fire and post-fire management of a Hymenoptera community from a
      Mediterranean protected area. Thus, Hymenoptera were sampled at fifteen sites
      located in three burnt areas submitted to different post-fire practices, as well
      as at five sites located in peripheral unburnt pine forest. A total of 4882
      specimens belonging to 33 families, which were classified into six feeding groups
      according to their dietary preferences, were collected. ANOVA and Redundancy
      Analyses showed a taxonomic and functional response to fire as all burnt areas
      had more Hymenoptera families, different community composition and higher numbers
      of parasitoids than the unburnt area. Taxonomic differences were also found
      between burnt areas in terms of the response of Hymenoptera to post-fire
      management. In general the number of parasitoids was positively correlated to the
      number of potential host arthropods. Parasitoids are recognized to be sensitive
      to habitat changes, thus highlighting their value for monitoring the functional
      responses of organisms to habitat disturbance. The taxonomic and functional
      responses of Hymenoptera suggest that some pine-forest fires can enhance habitat
      heterogeneity and arthropod diversity, hence increasing interspecific
      interactions such as those established by parasitoids and their hosts.

PMID- 21947368
TI  - Roadless and Low-Traffic Areas as Conservation Targets in Europe.
AB  - With increasing road encroachment, habitat fragmentation by transport
      infrastructures has been a serious threat for European biodiversity. Areas with
      no roads or little traffic ("roadless and low-traffic areas") represent
      relatively undisturbed natural habitats and functioning ecosystems. They provide
      many benefits for biodiversity and human societies (e.g., landscape connectivity,
      barrier against pests and invasions, ecosystem services). Roadless and low
      traffic areas, with a lower level of anthropogenic disturbances, are of special
      relevance in Europe because of their rarity and, in the context of climate
      change, because of their contribution to higher resilience and buffering capacity
      within landscape ecosystems. An analysis of European legal instruments
      illustrates that, although most laws aimed at protecting targets which are
      inherent to fragmentation, like connectivity, ecosystem processes or integrity,
      roadless areas are widely neglected as a legal target. A case study in Germany
      underlines this finding. Although the Natura 2000 network covers a significant
      proportion of the country (16%), Natura 2000 sites are highly fragmented and most
      low-traffic areas (75%) lie unprotected outside this network. This proportion is
      even higher for the old Federal States (western Germany), where only 20% of the
      low-traffic areas are protected. We propose that the few remaining roadless and
      low-traffic areas in Europe should be an important focus of conservation efforts;
      they should be urgently inventoried, included more explicitly in the law and
      accounted for in transport and urban planning. Considering them as complementary
      conservation targets would represent a concrete step towards the strengthening
      and adaptation of the Natura 2000 network to climate change.

PMID- 21947369
TI  - The prevalence of chronic psychological complaints and emotional exhaustion among
      overweight and obese workers.
AB  - PURPOSE: Literature suggests a relationship between overweight and obesity, and
      mental health problems, but data regarding prevalence rates are scarce. This
      study aimed to determine the prevalence of chronic psychological complaints and
      emotional exhaustion among overweight and obese workers. METHODS: Data were used
      from the Netherlands Working Conditions Survey (NWCS), which is representative
      for Dutch employees (n = 43,928). Based on self-reported body mass index (BMI),
      workers were classified into underweight, healthy weight, overweight, and
      obesity. Respondents indicated whether they suffered from chronic psychological
      complaints. Emotional exhaustion was measured by using the UBOS subscale.
      Logistic regression analyses were used to test differences in prevalence across
      weight categories, with healthy weight as the reference group. Analyses were
      stratified for gender, age, education, and occupation. RESULTS: Of the obese
      workers, 15.7% reported emotional exhaustion and 3.7% reported chronic
      psychological complaints. These prevalence rates were significantly higher than
      among healthy weight workers. A significant J shape was found with healthy weight
      workers reporting the lowest prevalence of both indicators of mental health
      problems. This J shape was generally also seen among the gender, age, education,
      and occupation subgroups, though not consistently significant. CONCLUSION:
      Considering the proportion of obese workers that also suffers from psychological
      co-morbidities, interventions targeting obesity should take this into account. As
      weight-related stigma may play a role in the risk for mental health problems
      among obese workers, future longitudinal research on the mechanisms for the
      relation between overweight and mental health problems are recommended.

PMID- 21947370
TI  - Mechanistic modeling of antigen sink effect for mavrilimumab following
      intravenous administration in patients with rheumatoid arthritis.
AB  - Mavrilimumab is a fully human monoclonal antibody that binds to granulocyte
      macrophage colony stimulating factor receptor alpha (GM-CSFRalpha) with high
      affinity and specificity and has potential application in various inflammatory
      diseases. The objective of this investigation was to develop a mechanistic
      population model to characterize the pharmacokinetics of mavrilimumab, the GM
      CSFRalpha-mediated clearance, and receptor occupancy following single intravenous
      dosing to patients with rheumatoid arthritis. The internalization rate of
      mavrilimumab-GM-CSFRalpha complex was fixed to a value determined from
      quantitative confocal fluorescent imaging. The estimated typical first-order
      clearance and the central and peripheral distribution volumes were 3.79 mL/kg/d,
      39.6 mL/kg, and 50.3 mL/kg, respectively. The systemic GM-CSFRalpha expression
      level was estimated to be 0.0782 nM, and the equilibrium dissociation constant
      (0.103 nM) was in good agreement with the monovalent affinity determined by
      surface plasmon resonance. By fitting to the observed pharmacokinetic data, the
      mechanistic model predicted that systemically greater than 90% GM-CSFRalpha
      blockade by mavrilimumab was achieved and maintained up to 4, 7, and 11 weeks
      following single 1-, 3-, and 10-mg/kg administrations, respectively. Posterior
      visual predictive check and bootstrapping suggest that the mechanistic model is
      reasonably robust and can be used to predict mavrilimumab exposure under various
      scenarios for future clinical trial design.

PMID- 21947371
TI  - Population pharmacokinetics of pegaptanib in patients with neovascular, age
      related macular degeneration.
AB  - The anti-vascular endothelial growth factor (VEGF) aptamer pegaptanib is
      eliminated primarily by renal clearance. Because renal function declines with
      age, pegaptanib exposure in patients with age-related macular degeneration (AMD)
      may increase. Therefore, a population pharmacokinetic (PK) analysis of pegaptanib
      was undertaken in Western and Asian AMD patients to determine the influence of
      renal function on apparent pegaptanib clearance (CL). Pegaptanib (0.3-3 mg per
      eye) was administered every 4 to 6 weeks to 262 AMD patients in 4 studies.
      Pegaptanib exposures (area under the concentration-time curve [AUC] and maximum
      plasma concentration) after 8 doses were similar to exposures following the first
      dose, consistent with the absence of plasma accumulation. A 1-compartment model
      parameterized in terms of the absorption rate constant, apparent volume of
      distribution, and CL was used to describe the pegaptanib plasma concentration
      data. Creatinine clearance (CLCR), body weight (WT), and age influenced
      pegaptanib PK. Decreasing CLCR from 70 to 30 mL/min doubled AUC. After adjustment
      for CLCR, WT, and age, the model predicted no race differences in CL or AUC.
      Given that the therapeutic 0.3 mg per eye dose of pegaptanib results in exposures
      one-tenth of those observed following the well-tolerated 3-mg dose, these results
      suggest that no dose adjustment is warranted for AMD patients with moderate renal
      insufficiency (CLCR >30 mL/min).

PMID- 21947372
TI  - QT dispersion and cardiac involvement in patients with juvenile idiopathic
      arthritis.
AB  - Juvenile idiopathic arthritis (JIA) is the commonest cause of chronic
      inflammatory arthritis in childhood. Cardiac involvement as pericarditis,
      myocarditis and valvular disease is known to occur in patients with JIA (JIA), as
      it does in adults with rheumatoid arthritis. There are, however, few descriptions
      concerning systolic and diastolic functions of the left ventricle (LV) in
      children with JIA. QT dispersion (QTd) is simple noninvasive arrhythmogenic
      marker that can be used to assess homogeneity of cardiac repolarization and which
      has not been studied in JIA patients before. A recent study found that rheumatoid
      arthritis patients had an abnormally longer QTd and corrected QT (cQTd)
      dispersion, markers for ventricular arrhythmogenicity. This study assessed QTd
      and cQTd and their relation with systolic and diastolic function of the LV in a
      group of children with JIA. We performed electrocardiography and Doppler
      echocardiography on patients and controls. Maximum QT (QTmax), minimum QT
      (QTmin), QTd, corrected QT, maximum corrected QT (cQTmax), minimum corrected QT
      (cQTmin) and cQTd intervals were measured from standard 12-lead
      electrocardiography. No statistically significant differences were found between
      the groups in QTd and cQTd. Among the diastolic parameters, increased late flow
      velocity, decreased early flow velocity and prolonged isovolumic relaxation time
      reflected an abnormal relaxation form of diastolic dysfunction. During 12 months
      of follow-up, no ventricular arrhythmias were documented in either group.

PMID- 21947373
TI  - The effect of spa therapy in chronic low back pain: a randomized controlled,
      single-blind, follow-up study.
AB  - Effect of thermal water with high mineral content on clinical parameters and
      quality of life of patients with chronic low back pain was studied. In this
      randomized controlled, single-blind, follow-up study, 60 patients with chronic
      low back pain were randomized into two groups. The treatment group received
      balneotherapy with thermal-mineral water, and the control group bathed in tap
      water. Changes of the followings were evaluated: visual analogue scale (VAS) for
      pain, range of motion for the lumbar spine, Oswestry index, EuroQol-5D and Short
      Form-36 questionnaires. In the treatment group, the mobility of the lumbar spine,
      the Oswestry index, the VAS scores and the EuroQoL-5D index improved
      significantly. SF-36 items improved significantly in the treated group compared
      with baseline except for two parameters. Our study demonstrated the beneficial
      effect of balneotherapy with thermal mineral versus tap water on clinical
      parameters, along with improvements in quality of life.

PMID- 21947374
TI  - The effects of combined spa therapy and rehabilitation on patients with
      ankylosing spondylitis being treated with TNF inhibitors.
AB  - Despite advances in pharmacological therapy, physical treatment continues to be
      important in the management of ankylosing spondylitis (AS). The objective of the
      present study was to evaluate the effects and tolerability of combined spa
      therapy and rehabilitation in a group of AS patients being treated with TNF
      inhibitors. Thirty AS patients attending the Rheumatology Unit of the University
      of Padova being treated with TNF inhibitors for at least 3 months were randomized
      and assessed by an investigator independent from the spa staff: 15 were
      prescribed 10 sessions of spa therapy (mud packs and thermal baths) and
      rehabilitation (exercises in a thermal pool) and the other 15 were considered
      controls. The patients in both groups had been receiving anti-TNF agents for at
      least three months. The outcome measures utilized were BASFI, BASDAI, BASMI, VAS
      for back pain and HAQ. The evaluations were performed in all patients at the
      entry to the study, at the end of the spa treatment, and after 3 and 6 months.
      Most of the evaluation indices were significantly improved at the end of the spa
      treatment, as well as at the 3 and 6 months follow-up assessments. No significant
      alterations in the evaluation indices were found in the control group. Combined
      spa therapy and rehabilitation caused a clear, long-term clinical improvement in
      AS patients being treated with TNF inhibitors. Thermal treatment was found to be
      well tolerated and none of the patients had disease relapse.

PMID- 21947375
TI  - Significant association between renal function and area of amyloid deposition in
      kidney biopsy specimens in reactive amyloidosis associated with rheumatoid
      arthritis.
AB  - The kidney is a major target organ for systemic amyloidosis, resulting in
      proteinuria and an elevated serum creatinine level. In patients with reactive
      amyloidosis associated with rheumatoid arthritis, a correlation between the
      amount of amyloid deposits and clinical parameters is not known. The purpose of
      this study was to clarify the association between various factors including renal
      function and the area of amyloid deposition in these patients. Fifty-eight
      patients with an established diagnosis of reactive AA amyloidosis were studied.
      We retrospectively investigated the correlation between clinical data and the
      area occupied by amyloid in renal biopsy specimens. All the patients showed
      amyloid deposits in renal tissues, and the percentage of the area occupied by
      amyloid was <10% in 54 of them. Mesangial proliferative glomerulonephritis and
      membranous nephropathy were frequently combined with renal amyloidosis. For
      statistical analyses, the percentage of the area occupied by amyloid was
      transformed to a common logarithmic value (Log(10) % amyloid), as the histograms
      showed a log-normal distribution. Log(10) % amyloid was found to be correlated
      with age, creatinine (Cr) level, creatinine clearance (Ccr), blood urea nitrogen
      (BUN) level, and the estimated glomerular filtration rate (eGFR). Multiple linear
      regression analyses were then performed to examine the sex- and age-adjusted
      association between Log(10) % amyloid and each of the clinical variables. Cr,
      Ccr, BUN, UA, CRP, and eGFR were significantly correlated with Log(10) % amyloid,
      but urinary protein was not. There was a significant correlation between the area
      of amyloid deposition in renal tissue and parameters of renal function,
      especially Cr and Ccr. If amyloid deposition in renal tissue can be arrested or
      prevented, then it may be possible to maintain renal function at an acceptable
      level.

PMID- 21947376
TI  - Bone density in Moroccan women with systemic scleroderma and its relationships
      with disease-related parameters and vitamin D status.
AB  - In this case-control study, our first aim was to evaluate the bone mineral
      density (BMD) in women with systemic sclerosis (SSc) and its correlates.
      Secondarily, we aimed to evaluate 25-hydroxyvitamin D3 status and its
      relationships with disease parameters and BMD. Sixty patients with SSc and 60 age
      and gender-matched controls were included in the absence of confounding factors
      that interfere with bone metabolism. Body mass index, menopausal status, familial
      history of osteoporosis and/or fractures; personal fracture history; exercise
      activity and laboratory parameters of bone metabolism were assessed in patients
      and controls. BMD was measured by using a dual-energy X-ray absorptiometry in
      lumbar spine (L1-L4) and femoral neck. The 25-hydroxyvitamin D3 was measured in a
      subgroup of 30 patients and in a subgroup of 30 matched controls. Systemic
      manifestations of SSc, biological inflammatory parameters, functional disability
      (scleroderma health assessment questionnaire (S-HAQ)) and immunological status of
      disease were collected in patients' group. The mean age of patients was 49.44 +/-
      13.07 years versus 49.55 +/- 12.11 in controls. The mean disease duration was
      9.63 +/- 5.9 years. SSc patients had a significantly earlier age and longer
      duration of menopause than controls (P = 0.003). Phosphocalcic metabolism
      parameters were within normal ranges in both groups. BMD was significantly lower
      in SSc patients than in controls both in lumbar spine (-2.97 +/- 0.25 in patients
      vs. 0.46 +/- 0.11 in controls) and femoral neck (-1.93 +/- 0.32 in patients vs. 
      0.81 +/- 0.69 in controls) (P < 0.01). Thirty-six (60%) patients versus 15 (25%)
      controls had osteoporosis and 19 (31.7%) patients versus 13 (21.7%) controls had
      osteopenia (P < 0.01). In correlation analysis and in multiple regression models,
      there were significant correlations between BMD and longer duration of SSc,
      severe joint involvement (severe joint pain and erosive arthropathy),
      malabsorption syndrome and the positivity of anti-DNA topoisomerase I antibodies.
      Also, we found very low levels of vitamin D (10.88 +/- 2.68 ng/ml) comparing to
      controls (57.41 +/- 4.18 ng/ml) (P = 0.001). Vitamin D levels were correlated
      with the severity of joint pain, with immunological status and with BMD in lumbar
      spine and femoral neck (P < 0.01). In our sample, we state the importance of
      decreased BMD in Moroccan women with SSc with a high frequency of osteoporosis
      comparing to healthy controls. Bone loss seems to be associated with prolonged
      disease duration, severe joint involvement, malabsorption syndrome and
      immunological status. Also, SSc patients had lower levels of 25-hydroxyvitamin D3
      than controls. Larger studies are needed to confirm those findings.

PMID- 21947377
TI  - Osteoporotic hip fractures in non-elderly patients: relevance of associated co
      morbidities.
AB  - Osteoporotic hip fractures (OHF) are not limited to elderly; however, studies in
      non-elderly are scarce. Thus, the aim of this study was to evaluate co
      morbidities in non-elderly patients with OHF in a Community Teaching Hospital.
      All hospitalizations due to OHF during a 3-year period in a Community Teaching
      Hospital were retrospectively evaluated for co-morbidities, and patients 18-64
      years old were compared with those >=65 years old. Of all hospitalizations, 232
      (0.73%) were due to hip fractures, and 120/232 (51.7%) patients had OHF. The
      comparison of the 13 (10.8%) OHF patients <65 years old (47.3 +/- 9.7 years) with
      107 (89.2%) >=65 years old (80.4 +/- 7.7 years) revealed a male predominance
      (61.5 vs. 27.1%, P = 0.022) and a distinct ethnic distribution with a lower
      proportion of Caucasians in the former (61.5 vs. 86.9%, P = 0.033). Moreover, non
      elderly OHF patients had higher frequencies of insulin-dependent DM (38.5 vs.
      3.7%, P = 0.001) and alcoholism (38.5 vs. 4.7%, P = 0.001) than aged patients. In
      contrast, rates of age-related co-morbidities such as stroke (7.7 vs. 18.7%, P =
      0.461), heart failure (23.1 vs. 14.0%, P = 0.411), and dementia (7.7 vs. 15.9%, P
      = 0.689) were comparable in both groups. Logistic regression analysis
      demonstrated that insulin-dependent DM (OR = 25.4, 95% CI = 4.7-136.8, P < 0.001)
      and alcoholism (OR = 20.3, 95% CI = 3.9-103.3, P < 0.001) remained as independent
      risk factors for OHF in non-elderly patients. Osteoporosis is an important cause
      of HF in Community Hospital. Non-elderly patients with OHF have a peculiar
      demographic profile and associated co-morbidities. These findings reinforce the
      need of early osteoporosis diagnosis and rigorous fracture prevention in patients
      with DM and alcoholism.

PMID- 21947378
TI  - Outcome of patients with connective tissue disease requiring intensive care for
      respiratory failure.
AB  - Occasionally acute respiratory failure (ARF) develops in patients with connective
      tissue disease (CTD), but the etiologies of ARF in these patients are not fully
      elucidated. The objective of this study is to find out the causes of ARF leading
      to intensive care unit (ICU) admission in these patients and to assess their
      clinical outcome. The medical records of 1,870 consecutive patients admitted to
      the ICU in Seoul National University Hospital since January 2005-September 2008
      were reviewed. A total of 66 patients with CTD were analyzed. The median age was
      58 years, and 45 patients were women. The median length of ICU stay was 16 days
      with a median duration of mechanical ventilation support of 15 days. The
      distribution of underlying CTD was 17 patients with systemic lupus erythematosus;
      15 with rheumatoid arthritis; 14 with systemic vasculitis; and nine with
      polymyositis-dermatomyositis. Pneumonia was the leading cause of ARF in 24
      patients (36%). We could not identify the cause of ARF in 14. Other causes of ARF
      were acute pulmonary edema for nine patients, diffuse alveolar hemorrhage for
      eight and Pneumocystis pneumonia for four. Forty-one patients (62%) died during
      admission, and the mortality rate was the lowest in those with acute pulmonary
      edema. Use of norepinephrine was statistically higher in nonsurvivors. We could
      identify the cause of ARF leading to ICU admission in at least 80% of patients
      with CTD. However, these patients still showed a high mortality rate regardless
      of etiology. Their survival might be influenced by hemodynamic status.

PMID- 21947379
TI  - Lymphoid hyperplasia of the thymus showing Castleman's disease in a patient with
      myasthenia gravis.

PMID- 21947380
TI  - Pancreatic islet and progenitor cell surface markers with cell sorting potential.
AB  - AIMS/HYPOTHESIS: The aim of the study was to identify surface bio-markers and
      corresponding antibody tools that can be used for the imaging and immunoisolation
      of the pancreatic beta cell and its progenitors. This may prove essential to
      obtain therapeutic grade human beta cells via stem cell differentiation. METHODS:
      Using bioinformatics-driven data mining, we generated a gene list encoding
      putative plasma membrane proteins specifically expressed at distinct stages of
      the developing pancreas and islet beta cells. In situ hybridisation and
      immunohistochemistry were used to further prioritise and identify candidates.
      RESULTS: In the developing pancreas seizure related 6 homologue like (SEZ6L2),
      low density lipoprotein receptor-related protein 11 (LRP11), dispatched homologue
      2 (Drosophila) (DISP2) and solute carrier family 30 (zinc transporter), member 8
      (SLC30A8) were found to be expressed in early islet cells, whereas discoidin
      domain receptor tyrosine kinase 1 (DDR1) and delta/notch-like EGF repeat
      containing (DNER) were expressed in early pancreatic progenitors. The expression
      pattern of DDR1 overlaps with the early pancreatic and duodenal homeobox 1
      (PDX1)+/NK6 homeobox 1 (NKX6-1)+ multipotent progenitor cells from embryonic day
      11, whereas DNER expression in part overlaps with neurogenin 3 (NEUROG3)+ cells.
      In the adult pancreas SEZ6L2, LRP11, DISP2 and SLC30A8, but also FXYD domain
      containing ion transport regulator 2 (FXYD2), tetraspanin 7 (TSPAN7) and
      transmembrane protein 27 (TMEM27), retain an islet-specific expression, whereas
      DDR1 is undetectable. In contrast, DNER is expressed at low levels in peripheral
      mouse and human islet cells. Re-expression of DDR1 and upregulation of DNER is
      observed in duct-ligated pancreas. Antibodies to DNER and DISP2 have been
      successfully used in cell sorting. CONCLUSIONS/INTERPRETATION: Extracellular
      epitopes of SEZ6L2, LRP11, DISP2, DDR1 and DNER have been identified as useful
      tags by applying specific antibodies to visualise pancreatic cell types at
      specific stages of development. Furthermore, antibodies recognising DISP2 and
      DNER are suitable for FACS-mediated cell purification.

PMID- 21947381
TI  - Glomerular filtration rate estimation in patients with type 2 diabetes:
      creatinine- or cystatin C-based equations?
AB  - AIMS/HYPOTHESIS: It is argued that GFR estimation (eGFR) using cystatin C-based
      equations (eGFRcys) is superior to that using creatinine-based equations
      (eGFRcre). We investigated whether eGFRcys are superior to eGFRcre in patients
      with type 2 diabetes. METHODS: GFR was measured in 448 type 2 diabetic patients
      using (51)Cr-EDTA-measured GFR (mGFR) as the reference standard. Bias, precision
      and accuracy of eGFRcys and eGFRcre were compared. RESULTS: The most accurate
      eGFRcre equation (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]),
      which produced the highest proportion of estimates that were within 30% and 10%
      of the reference standard (80.7% and 38.0% of samples, respectively) had a bias
      of 7.1 and precision of 12.0 ml min(-1) 1.73 m(-2). The calibrated eGFRcys with
      the highest accuracy (Tan-C), which produced the highest proportion of estimates
      that were within 30% (78.8%) and within 10% (39.0%) of the reference standard had
      a bias of -3.5 and precision of 18.0 ml min(-1) 1.73 m(-2). Moreover, the areas
      under the receiver operating curve were higher with eGFRcre (CKD-EPI and
      Modification of Diet in Renal Disease [MDRD]) than with eGFRcys for the diagnosis
      of mild (mGFR <90 ml min(-1) 1.73 m(-2)) and moderate (mGFR <60 ml min(-1) 1.73
      m(-2)) chronic kidney disease. In patients with mGFR >=90 ml min(-1) 1.73 m(-2),
      CKD-EPI was the least biased, the most precise and the most accurate equation.
      CONCLUSIONS/INTERPRETATION: In patients with type 2 diabetes, eGFRcys do not
      currently provide better eGFR than eGFRcre. At present, compared with eGFRcys,
      eGFRcre are better at predicting the stage of chronic kidney disease. In
      addition, CKD-EPI seems to be the best equation for eGFR in patients with normal
      renal function.

PMID- 21947382
TI  - Metformin activates AMP-activated protein kinase in primary human hepatocytes by
      decreasing cellular energy status.
AB  - AIM/HYPOTHESIS: The glucose-lowering drug metformin has been shown to activate
      hepatic AMP-activated protein kinase (AMPK), a master kinase regulating cellular
      energy homeostasis. However, the underlying mechanisms remain controversial and
      have never been investigated in primary human hepatocytes. METHODS: Hepatocytes
      isolated from rat, mouse and human livers were treated with various
      concentrations of metformin. Isoform-specific AMPKalpha abundance and activity,
      as well as intracellular adenine nucleotide levels and mitochondrial oxygen
      consumption rates were determined at different time points. RESULTS: Metformin
      dose- and time-dependently increased AMPK activity in rat and human hepatocytes,
      an effect associated with a significant rise in cellular AMP:ATP ratio.
      Surprisingly, we found that AMPKalpha2 activity was undetectable in human
      compared with rat hepatocytes, while AMPKalpha1 activities were comparable.
      Accordingly, metformin only increased AMPKalpha1 activity in human hepatocytes,
      although both AMPKalpha isoforms were activated in rat hepatocytes. Analysis of
      mRNA expression and protein levels confirmed that only AMPKalpha1 is present in
      human hepatocytes; it also showed that the distribution of beta and gamma
      regulatory subunits differed between species. Finally, we demonstrated that the
      increase in AMP:ATP ratio in hepatocytes from liver-specific Ampkalpha1/2 (also
      known as Prkaa1/2) knockout mice and humans is due to a similar and specific
      inhibition of the mitochondrial respiratory-chain complex 1 by metformin.
      CONCLUSIONS/INTERPRETATION: Activation of hepatic AMPK by metformin results from
      a decrease in cellular energy status owing to metformin's AMPK-independent
      inhibition of the mitochondrial respiratory-chain complex 1. The unique profile
      of AMPK subunits found in human hepatocytes should be considered when developing
      new pharmacological agents to target the kinase.

PMID- 21947383
TI  - Efficacy of renin-angiotensin system (RAS) blockers on cardiovascular and renal
      outcomes in patients with type 2 diabetes.
AB  - Cardiovascular disease is the predominant cause of morbidity in people with type
      2 diabetes. Hypertension frequently coexists with diabetes and substantially
      increases the risk of developing end-organ damage. Controlling hypertension in
      patients with diabetes is therefore critical to reducing microvascular and
      macrovascular complications. Agents that block the renin-angiotensin system are
      increasingly used in patients with diabetes based on their cardiovascular and
      renoprotective effects, in addition to their direct effects on reducing blood
      pressure. Telmisartan, an angiotensin II receptor blocker (ARB), has a number of
      distinguishing pharmacological properties such as having the longest half-life
      and highest lipophilicity in its class. The ONgoing Telmisartan Alone and in
      combination with Ramipril Global Endpoint Trial (ONTARGET((r))) trial showed that
      telmisartan reduces cardiovascular morbidity (including myocardial infarction and
      stroke) in subjects with a broad spectrum of cardiovascular risk factors,
      including type 2 diabetes. Telmisartan is the only ARB indicated for the
      reduction of cardiovascular morbidity in patients with diabetes and end-organ
      damage, as well as in patients without diabetes but with a history of coronary
      artery disease, peripheral artery disease, or previous stroke. Trials of
      telmisartan in patients with diabetes and varying degrees of nephropathy also
      suggest that this drug can slow the progression of renal disease, an effect that
      appears to be at least partly independent of reduction in blood pressure.
      Telmisartan is therefore an important therapeutic option for optimizing
      cardiovascular and renal protection in the type 2 diabetic population.

PMID- 21947384
TI  - Angiogenesis regulatory factors in the vitreous from patients with proliferative
      diabetic retinopathy.
AB  - We determined the levels of the endogenous angiogenesis inhibitors soluble
      vascular endothelial growth factor receptor-1 (sVEGFR-1), thrombospondin (TSP)-1
      and TSP-2 in the vitreous fluid from patients with proliferative diabetic
      retinopathy (PDR) and correlated their levels with clinical disease activity and
      the levels of vascular endothelial growth factor (VEGF). Vitreous samples from 30
      PDR and 25 nondiabetic patients were studied by enzyme-linked immunosorbent
      assay. TSP-1 was not detected. VEGF and TSP-2 levels were significantly higher in
      PDR with active neovascularization compared with inactive PDR and nondiabetic
      patients (P < 0.001 for both comparisons). VEGF, sVEGFR-1 and TSP-2 levels were
      significantly higher in PDR with hemorrhage compared with PDR without hemorrhage
      and nondiabetic patients (P = 0.0063; 0.0144; <0.001, respectively). VEGF and
      sVEGFR-1 levels were significantly higher in PDR without traction retinal
      detachment (TRD) compared with PDR with TRD and nondiabetic patients (P = 0.038;
      0.022, respectively). TSP-2 levels were significantly higher in PDR with TRD
      compared with PDR without TRD and nondiabetic patients (P < 0.001). There was a
      significant correlation between levels of VEGF and sVEGFR-1 (r = 0.427, P =
      0.038). Our findings suggest that upregulation of sVEGFR-1 and TSP-2 may be a
      protective mechanism against progression of angiogenesis associated with PDR. TSP
      2 might be associated with TRD.

PMID- 21947385
TI  - Activation of nuclear factor-kappa B by linear ubiquitin chain assembly complex
      contributes to lung metastasis of osteosarcoma cells.
AB  - NF-kappaB is involved in the metastasis of malignant cells. We have shown that NF
      kappaB activation is involved in the pulmonary metastasis of LM8 cells, a highly
      metastatic subclone of Dunn murine osteosarcoma cells. Recently, it was
      determined that a newly identified type of polyubiquitin chain, a linear
      polyubiquitin chain, which is specifically generated by the linear ubiquitin
      chain assembly complex (LUBAC), plays a critical role in NF-kappaB activation.
      Here, we have evaluated the roles of LUBAC-mediated NF-kappaB activation in the
      development of lung metastasis of osteosarcoma cells. All three components of
      LUBAC (HOIL-1L, HOIP and SHARPIN) were highly expressed in LM8 cells compared to
      Dunn cells. Attenuation of LUBAC expression by stable knockdown of HOIL-1L in LM8
      cells significantly suppressed NF-kappaB activity, invasiveness in vitro and lung
      metastasis. Induction of intracellular adhesion molecule-1 (ICAM-1) expression by
      LUBAC is involved in cell retention in the lungs after an intravenous inoculation
      of tumor cells. Moreover, we found that knockdown of LUBAC decreased not only the
      number but also the size of the metastatic nodules of LM8 cells in the lungs.
      These results indicate that LUBAC-mediated NF-kappaB activation plays crucial
      roles in several steps involved in metastasis, including extravasation and growth
      of osteosarcoma cells in the lung, and that suppression of LUBAC-mediated linear
      polyubiquitination activity may be a new approach to treat this life-threatening
      disease of young adolescents.

PMID- 21947386
TI  - Meta-analysis and systematic review of procalcitonin-guided therapy in
      respiratory tract infections.
AB  - Circulating procalcitonin (PCT) is a biomarker that can be used in diagnosing
      bacterial infections. We performed a quantitative meta-analysis of available
      randomized controlled trials to determine whether antibiotic therapy based on PCT
      measurements alters clinical outcomes and antibiotic use in patients with lower
      respiratory tract infections. We identified studies through MEDLINE (1996 to
      2010), the ISI Web of Knowledge (1996 to 2010), and Ovid. Studies that met our
      criteria were prospective, randomized controlled trials involving patients with
      respiratory tract infections. Outcomes of mortality, intensive care unit (ICU)
      admission, length of hospital stay, number of antibiotic prescriptions, and
      duration of antibiotic treatment were evaluated. Eight studies randomizing 3,431
      patients met our criteria for inclusion. Pooled analysis showed a significant
      reduction in number of antibiotic prescriptions and duration of antibiotic use in
      patients with PCT-guided antibiotic treatment compared to standard therapy. In
      addition, the use of PCT-guided antibiotic therapy did not impact mortality, ICU
      admission, or length of hospital stay in these studies. A high degree of
      heterogeneity was identified in 3 of 5 outcomes that were evaluated, and
      sensitivity analysis indicated that heterogeneity was decreased among studies
      using the same PCT-based treatment algorithm. In conclusion, PCT-guided
      antibiotic therapy in patients with respiratory tract infections appears to
      reduce antibiotic use without affecting overall mortality or length of stay in
      the hospital.

PMID- 21947387
TI  - A novel benzodioxole-containing inhibitor of Toxoplasma gondii growth alters the
      parasite cell cycle.
AB  - Toxoplasma gondii is an obligate intracellular parasite that can cause disease in
      the developing fetus and in immunocompromised humans. Infections can last for the
      life of the individual, and to date there are no drugs that eliminate the chronic
      cyst stages that are characteristic of this parasite. In an effort to identify
      new chemical scaffolds that could form the basis for new therapeutics, we carried
      out a chemoinformatic screen for compounds that had the potential to interact
      with members of a superfamily of parasite-secreted kinases and assayed them for
      growth inhibition in vitro. Of 17 candidate compounds, we identified one with
      potent antiparasitic activity. The compound has a 50% inhibitory concentration
      (IC(50)) of ~2 nM, and structure-function analyses implicate the benzodioxole
      moiety in its action. The compound does not appear to be cytotoxic to host cells.
      Using microarray analyses of both parasites and host cells treated with the
      compound, we found that the levels of very few host cell transcripts are altered
      by the compound, while a large number of parasite transcripts have a different
      abundance after compound treatment. Gene ontology analyses of parasite
      transcripts with a different abundance revealed an enrichment of cell cycle
      related genes, suggesting that the compound alters progression of the parasite
      through the cell cycle. Assaying the nuclear content of treated parasites
      demonstrated that compound treatment significantly increased the percentage of
      parasites in the S/M phase of the cell cycle compared to controls. This compound
      and its analogs represent a novel scaffold with antiparasitic activity.

PMID- 21947388
TI  - Relationship between vancomycin trough concentrations and nephrotoxicity: a
      prospective multicenter trial.
AB  - Several single-center studies have suggested that higher doses of vancomycin,
      aimed at producing trough concentrations of >15 mg/liter, are associated with
      increased risk of nephrotoxicity. We prospectively assessed the relative
      incidence of nephrotoxicity in relation to trough concentration in patients with
      documented methicillin-resistant Staphylococcus aureus (MRSA) infections at seven
      hospitals throughout South Carolina. Adult patients receiving vancomycin for at
      least 72 h with at least one vancomycin trough concentration determined under
      steady-state conditions were prospectively studied. The relationship between
      vancomycin trough concentrations of >15 mg/ml and the occurrence of
      nephrotoxicity was assessed using univariate and multivariate analyses,
      controlling for age, gender, race, dose, length of therapy, use of other
      nephrotoxins (including contrast media), intensive care unit (ICU) residence,
      episodes of hypotension, and comorbidities. Nephrotoxicity was defined as an
      increase in serum creatinine of 0.5 mg/dl or a >= 50% increase from the baseline
      for two consecutive measurements. MICs of vancomycin for the MRSA isolates were
      also determined. A total of 288 patients were studied between February 2008 and
      June 2010, with approximately one-half having initial trough concentrations of >=
      15 mg/ml. Nephrotoxicity was observed for 42 patients (29.6%) with trough
      concentrations >15 mg/ml and for 13 (8.9%) with trough concentrations of <= 15
      mg/ml. Multivariate analysis revealed vancomycin trough concentrations of >15
      mg/ml and race (black) as risk factors for nephrotoxicity in this population.
      Vancomycin trough concentrations of >15 mg/ml appear to be associated with a 3
      fold increased risk of nephrotoxicity.

PMID- 21947389
TI  - Randomized, double-blind, phase II, multicenter study evaluating the
      safety/tolerability and efficacy of JNJ-Q2, a novel fluoroquinolone, compared
      with linezolid for treatment of acute bacterial skin and skin structure
      infection.
AB  - JNJ-Q2 is a fluoroquinolone with broad coverage including methicillin-resistant
      Staphylococcus aureus (MRSA). A double-blind, multicenter, phase II
      noninferiority study treated 161 patients for 7 to 14 days, testing the efficacy
      of JNJ-Q2 (250 mg, twice a day [BID]) versus linezolid (600 mg, BID) in patients
      with acute bacterial skin and skin structure infections (ABSSSI). The
      prespecified criterion for noninferiority was 15%. Primary intent-to-treat
      analysis was unable to declare noninferiority, as the risk difference lower bound
      of the 95% confidence interval between treatments was 19% at 36 to 84 h
      postrandomization for the composite end point of lesion assessment and
      temperature. Prespecified clinical cure rates 2 to 14 days after completion of
      therapy were similar (83.1% for JNJ-Q2 versus 82.1% for linezolid). Post hoc
      analyses revealed that JNJ-Q2 was statistically noninferior to linezolid (61.4%
      versus 57.7%, respectively; P = 0.024) based on the 2010 FDA guidance, which
      defines treatment success as lack of lesion spread and afebrile status within 48
      to 72 h postrandomization. Despite evidence of systemic disease, <5% of patients
      presented with fever, suggesting fever is not a compelling surrogate measure of
      systemic disease resolution for this indication. Nausea and vomiting were the
      most common adverse events. Of the patients, 86% (104/121) had S. aureus isolated
      from the infection site; 63% of these were MRSA. The results suggest JNJ-Q2 shows
      promise as an effective treatment for ABSSSI, demonstrating (i) efficacy for
      early clinical response (i.e., lack of spread of lesions and absence of fever at
      48 to 72 h), and (ii) cure rates for ABSSSI pathogens (especially MRSA)
      consistent with the historical literature.

PMID- 21947390
TI  - Quantifying the impact of nevirapine-based prophylaxis strategies to prevent
      mother-to-child transmission of HIV-1: a combined pharmacokinetic,
      pharmacodynamic, and viral dynamic analysis to predict clinical outcomes.
AB  - Single-dose nevirapine (sd-NVP) and extended NVP prophylaxis are widely used in
      resource-constrained settings to prevent vertical HIV-1 transmission. We assessed
      the pharmacokinetics of sd-NVP in 62 HIV-1-positive pregnant Ugandan woman and
      their newborns who were receiving sd-NVP prophylaxis to prevent mother-to-child
      HIV-1 transmission. Based on these data, we developed a mathematical model system
      to quantify the impact of different sd-NVP regimens at delivery and of extended
      infant NVP prophylaxis (6, 14, 21, 26, 52, 78, and 102 weeks) on the 2-year risk
      of HIV-1 transmission and development of drug resistance in mothers and their
      breast-fed infants. Pharmacokinetic parameter estimates and model-predicted HIV-1
      transmission rates were very consistent with other studies. Predicted 2-year HIV
      1 transmission risks were 35.8% without prophylaxis, 31.6% for newborn sd-NVP,
      19.1% for maternal sd-NVP, and 19.7% for maternal/newborn sd-NVP. Maternal sd-NVP
      reduced newborn infection predominately by transplacental exchange, providing
      protective NVP concentrations to the newborn at delivery, rather than by maternal
      viral load reduction. Drug resistance was frequently selected in HIV-1-positive
      mothers after maternal sd-NVP. Extended newborn NVP prophylaxis further decreased
      HIV-1 transmission risks, but an overall decline in cost-effectiveness for
      increasing durations of newborn prophylaxis was indicated. The total number of
      infections with resistant virus in newborns was not increased by extended newborn
      NVP prophylaxis. The developed mathematical modeling framework successfully
      predicted the risk of HIV-1 transmission and resistance development and can be
      adapted to other drugs/drug combinations to a priori assess their potential in
      reducing vertical HIV-1 transmission and resistance spread.

PMID- 21947391
TI  - Differential association of Plasmodium falciparum Na+/H+ exchanger polymorphism
      and quinine responses in field- and culture-adapted isolates of Plasmodium
      falciparum.
AB  - Plasmodium falciparum isolates with decreased susceptibility to quinine are
      increasingly being found in malaria patients. Mechanisms involved in this
      resistance are not yet understood. Several studies claim that alongside mutations
      in the Pfcrt and Pfmdr1 genes, the Pfnhe-1 Na(+)/H(+) exchanger polymorphism
      plays a role in decreasing susceptibility. However, conflicting results on the
      link between the Pfnhe-1 gene and quinine resistance arise from field- and
      culture-adapted isolates. We tested the association between Pfnhe-1, Pfcrt, and
      Pfmdr1 polymorphisms in field- and culture-adapted isolates from various
      countries with their in vitro susceptibility to quinine. Field isolates presented
      a higher diversity of the Pfnhe-1 microsatellite sequence than culture-adapted
      isolates. In culture-adapted isolates but not in field isolates, mutations in the
      Pfcrt and Pfmdr1 genes, as well as a higher number of DNNND repeats in the Pfnhe
      1 gene, were associated with a higher 50% inhibitory concentration (IC(50)) of
      quinine. Furthermore, most of the culture-adapted isolates with more than one
      DNNND repeat in the Pfnhe-1 gene also harbored mutated Pfcrt and Pfmdr1 genes
      with an apparent cumulative effect on quinine susceptibility. This study supports
      the involvement of the Pfnhe-1 gene in the modulation of the in vitro quinine
      response when associated with mutated Pfcrt and Pfmdr1 genes. Culture adaptation
      could be responsible for selection of specific haplotypes of these three genes.
      Methods used for drug testing might thus influence the association between Pfnhe
      1 polymorphism and quinine susceptibility. However, we do not exclude the
      possibility that in particular settings, Pfnhe-1 polymorphism can be used as a
      molecular marker for surveillance of quinine resistance.

PMID- 21947392
TI  - Pharmacokinetics of dihydroartemisinin and piperaquine in pregnant and
      nonpregnant women with uncomplicated falciparum malaria.
AB  - Dihydroartemisinin-piperaquine is a fixed-dose artemisinin-based combination
      treatment. Some antimalarials have altered pharmacokinetics in pregnancy.
      Pregnant women in the 2nd or 3rd trimester and matched nonpregnant women with
      uncomplicated falciparum malaria were treated with a total of 6.4 mg/kg of body
      weight dihydroartemisinin and 51.2 mg/kg piperaquine once daily for 3 days.
      Venous blood samples were drawn at prespecified time points over 9 weeks. Plasma
      dihydroartemisinin and piperaquine concentrations were analyzed by liquid
      chromatography-mass spectrometry. Piperaquine and dihydroartemisinin
      pharmacokinetics were well described. There were no significant differences in
      total piperaquine exposure (P = 0.80) or drug exposure during the terminal
      elimination phase (72 h to infinity) (P = 0.64) between the two groups. The
      apparent volume of distribution of piperaquine was significantly smaller (602
      liters/kg versus 877 liters/kg) in pregnant women than in nonpregnant women (P =
      0.0057), and the terminal elimination half-life was significantly shorter (17.8
      days versus 25.6 days; P = 0.0023). Dihydroartemisinin exposure after the first
      dose was significantly lower (844 h * ng/ml versus 1,220 h * ng/ml, P = 0.0021)
      in pregnant women, but there were no significant differences in total
      dihydroartemisinin exposure or maximum concentrations between the two groups.
      There were no significant differences in any pharmacokinetic parameters between
      the second and third trimester. These results obtained through noncompartmental
      analysis suggest that in the treatment of falciparum malaria, there are no
      clinically important differences in the pharmacokinetics of dihydroartemisinin or
      piperaquine between pregnant and nonpregnant women. However, a more detailed
      analysis using population pharmacokinetic modeling is needed to fully investigate
      the differences found for some of the pharmacokinetic parameters, such as the
      terminal half-life.

PMID- 21947393
TI  - Clinical pharmacokinetics of meropenem and biapenem in bile and dosing
      considerations for biliary tract infections based on site-specific
      pharmacodynamic target attainment.
AB  - The present study investigated the pharmacokinetics of meropenem and biapenem in
      bile and estimated their pharmacodynamic target attainment at the site. Meropenem
      (0.5 g) or biapenem (0.3 g) was administered to surgery patients (n = 8 for each
      drug). Venous blood samples and hepatobiliary tract bile samples were obtained at
      the end of infusion (0.5 h) and for up to 5 h thereafter. Drug concentrations in
      plasma and bile were analyzed pharmacokinetically and used for a Monte Carlo
      simulation to predict the probability of attaining the pharmacodynamic target
      (40% of the time above the MIC). Both drugs penetrated similarly into bile, with
      mean bile/plasma ratios of 0.24 to 0.25 (maximum drug concentration) and 0.30 to
      0.38 (area under the drug concentration-time curve). The usual regimens of
      meropenem (0.5 g every 8 h [q8h]) and biapenem (0.3 g q8h) (0.5-h infusions)
      achieved similar target attainment probabilities in bile (>= 90%) against
      Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae isolates.
      However, against Pseudomonas aeruginosa isolates, meropenem at 1 g q8h and
      biapenem at 0.6 g q8h were required for values of 80.7% and 71.9%, respectively.
      The biliary pharmacodynamic-based breakpoint (the highest MIC at which the target
      attainment probability in bile was >= 90%) was 1 mg/liter for 0.5 g q8h and 2
      mg/liter for 1 g q8h for meropenem and 0.5 mg/liter for 0.3 g q8h and 1 mg/liter
      for 0.6 g q8h for biapenem. These results help to define the clinical
      pharmacokinetics of the two carbapenems in bile while also helping to rationalize
      and optimize the dosing regimens for biliary tract infections based on site
      specific pharmacodynamic target attainment.

PMID- 21947394
TI  - An Escherichia coli O157-specific engineered pyocin prevents and ameliorates
      infection by E. coli O157:H7 in an animal model of diarrheal disease.
AB  - AvR2-V10.3 is an engineered R-type pyocin that specifically kills Escherichia
      coli O157, an enteric pathogen that is a major cause of food-borne diarrheal
      disease. New therapeutics to counteract E. coli O157 are needed, as currently
      available antibiotics can exacerbate the consequences of infection. We show here
      that orogastric administration of AvR2-V10.3 can prevent or ameliorate E. coli
      O157:H7-induced diarrhea and intestinal inflammation in an infant rabbit model of
      infection when the compound is administered either in a postexposure prophylactic
      regimen or after the onset of symptoms. Notably, administration of AvR2-V10.3
      also reduces bacterial carriage and fecal shedding of this pathogen. Our findings
      support the further development of pathogen-specific R-type pyocins as a way to
      treat enteric infections.

PMID- 21947395
TI  - Role of Aspergillus lentulus 14-alpha sterol demethylase (Cyp51A) in azole drug
      susceptibility.
AB  - Recent studies have demonstrated that some morphologically atypical Aspergillus
      fumigatus strains are different species belonging to the section Fumigati.
      Aspergillus lentulus, one of these sibling species, is increasingly reported in
      patients under corticosteroid treatment. MICs of most antifungals in clinical use
      are elevated against A. lentulus, and it shows primary resistance to azole drugs.
      Two A. lentulus cytochrome P450 14-alpha sterol demethylases, encoded by A.
      lentulus cyp51A (Alcyp51A) and Alcyp51B genes, were identified. Targeted cyp51A
      gene knockout in A. lentulus showed that the intrinsic azole resistance of this
      species is cyp51A dependent. The Deltacyp51A strain was morphologically
      indistinguishable from the A. lentulus wild-type strain, retaining the ability to
      cause pulmonary disease in neutropenic mice. The heterologous expression of A.
      lentulus cyp51A was performed in an A. fumigatus cyp51A-deficient strain,
      confirming that Cyp51A is responsible for the differences in A. lentulus-azole
      drug interaction.

PMID- 21947396
TI  - The antibacterial activity of Ga3+ is influenced by ligand complexation as well
      as the bacterial carbon source.
AB  - Gallium ions have previously been shown to exhibit antibacterial and antibiofilm
      properties. In this study, we report differential bactericidal activities of two
      gallium complexes, gallium desferrioxamine B (Ga-DFOB) and gallium citrate (Ga
      Cit). Modeling of gallium speciation in growth medium showed that DFOB and
      citrate both can prevent precipitation of Ga(OH)(3), but some precipitation can
      occur above pH 7 with citrate. Despite this, Ga-Cit 90% inhibitory concentrations
      (IC(90)) were lower than those of Ga-DFOB for clinical isolates of Pseudomonas
      aeruginosa and several reference strains of other bacterial species. Treatment
      with Ga compounds mitigated damage inflicted on murine J774 macrophage-like cells
      infected with P. aeruginosa PAO1. Again, Ga-Cit showed more potent mitigation
      than did Ga-DFOB. Ga was also taken up more efficiently by P. aeruginosa in the
      form of Ga-Cit than in the form of Ga-DFOB. Neither Ga-Cit nor Ga-DFOB was toxic
      to several human cell lines tested, and no proinflammatory activity was detected
      in human lung epithelial cells after exposure in vitro. Metabolomic analysis was
      used to delineate the effects of Ga-Cit on the bacterial cell. Exposure to Ga
      resulted in lower concentrations of glutamate, a key metabolite for P.
      aeruginosa, and of many amino acids, indicating that Ga affects various
      biosynthesis pathways. An altered protein expression profile in the presence of
      Ga-Cit suggested that some compensatory mechanisms were activated in the
      bacterium. Furthermore, the antibacterial effect of Ga was shown to vary
      depending on the carbon source, which has importance in the context of medical
      applications of gallium.

PMID- 21947397
TI  - Molecular characterization of resistance to extended-spectrum cephalosporins in
      clinical Escherichia coli isolates from companion animals in the United States.
AB  - Resistance to extended-spectrum cephalosporins (ESC) among members of the family
      Enterobacteriaceae occurs worldwide; however, little is known about ESC
      resistance in Escherichia coli strains from companion animals. Clinical isolates
      of E. coli were collected from veterinary diagnostic laboratories throughout the
      United States from 2008 to 2009. E. coli isolates (n = 54) with reduced
      susceptibility to ceftazidime or cefotaxime (MIC >= 16 MUg/ml) and extended
      spectrum-beta-lactamase (ESBL) phenotypes were analyzed. PCR and sequencing were
      used to detect mutations in ESBL-encoding genes and the regulatory region of the
      chromosomal gene ampC. Conjugation experiments and plasmid identification were
      conducted to examine the transferability of resistance to ESCs. All isolates
      carried the bla(CTX-M-1)-group beta-lactamase genes in addition to one or more of
      the following beta-lactamase genes: bla(TEM), bla(SHV-3), bla(CMY-2), bla(CTX-M
      14-like), and bla(OXA-1.) Different bla(TEM) sequence variants were detected in
      some isolates (n = 40). Three isolates harbored a bla(TEM-181) gene with a novel
      mutation resulting in an Ala184Val substitution. Approximately 78% of the
      isolates had mutations in promoter/attenuator regions of the chromosomal gene
      ampC, one of which was a novel insertion of adenine between bases -28 and -29.
      Plasmids ranging in size from 11 to 233 kbp were detected in the isolates, with a
      common plasmid size of 93 kbp identified in 60% of isolates. Plasmid-mediated
      transfer of beta-lactamase genes increased the MICs (>= 16-fold) of ESCs for
      transconjugants. Replicon typing among isolates revealed the predominance of IncI
      and IncFIA plasmids, followed by IncFIB plasmids. This study shows the emergence
      of conjugative plasmid-borne ESBLs among E. coli strains from companion animals
      in the United States, which may compromise the effective therapeutic use of ESCs
      in veterinary medicine.

PMID- 21947398
TI  - Zinc pyrithione inhibits yeast growth through copper influx and inactivation of
      iron-sulfur proteins.
AB  - Zinc pyrithione (ZPT) is an antimicrobial material with widespread use in
      antidandruff shampoos and antifouling paints. Despite decades of commercial use,
      there is little understanding of its antimicrobial mechanism of action. We used a
      combination of genome-wide approaches (yeast deletion mutants and microarrays)
      and traditional methods (gene constructs and atomic emission) to characterize the
      activity of ZPT against a model yeast, Saccharomyces cerevisiae. ZPT acts through
      an increase in cellular copper levels that leads to loss of activity of iron
      sulfur cluster-containing proteins. ZPT was also found to mediate growth
      inhibition through an increase in copper in the scalp fungus Malassezia globosa.
      A model is presented in which pyrithione acts as a copper ionophore, enabling
      copper to enter cells and distribute across intracellular membranes. This is the
      first report of a metal-ligand complex that inhibits fungal growth by increasing
      the cellular level of a different metal.

PMID- 21947399
TI  - Interaction between artemether-lumefantrine and nevirapine-based antiretroviral
      therapy in HIV-1-infected patients.
AB  - Artemether-lumefantrine and nevirapine-based antiretroviral therapy (ART) are the
      most commonly recommended first-line treatments for malaria and HIV,
      respectively, in Africa. Artemether, lumefantrine, and nevirapine are metabolized
      by the cytochrome P450 3A4 enzyme system, which nevirapine induces, creating
      potential for important drug interactions. In a parallel-design pharmacokinetic
      study, concentration-time profiles were obtained in two groups of HIV-infected
      patients: ART-naive patients and those stable on nevirapine-based therapy. Both
      groups received the recommended artemether-lumefantrine dose. Patients were
      admitted for intense pharmacokinetic sampling (0 to 72 h) with outpatient
      sampling until 21 days. Concentrations of lumefantrine, artemether,
      dihydroartemisinin, and nevirapine were determined by validated liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) methods. The primary outcome
      was observed day 7 lumefantrine concentrations, as these are associated with
      therapeutic response in malaria. We enrolled 36 patients (32 females). Median
      (range) day 7 lumefantrine concentrations were 622 ng/ml (185 to 2,040 ng/ml) and
      336 ng/ml (29 to 934 ng/ml) in the nevirapine and ART-naive groups, respectively
      (P = 0.0002). The median artemether area under the plasma concentration-time
      curve from 0 to 8 h [AUC((0-8 h))] (P < 0.0001) and dihydroartemisinin AUC((60-68
      h)) (P = 0.01) were lower in the nevirapine group. Combined artemether and
      dihydroartemisinin exposure decreased over time only in the nevirapine group
      (geometric mean ratio [GMR], 0.76 [95% confidence interval {CI}, 0.65 to 0.90]; P
      < 0.0001) and increased with the weight-adjusted artemether dose (GMR, 2.12 [95%
      CI, 1.31 to 3.45]; P = 0.002). Adverse events were similar between groups, with
      no difference in electrocardiographic Fridericia corrected QT and P-R intervals
      at the expected time of maximum lumefantrine concentration (T(max)). Nevirapine
      based ART decreased artemether and dihydroartemisinin AUCs but unexpectedly
      increased lumefantrine exposure. The mechanism of the lumefantrine interaction
      remains to be elucidated. Studies investigating the interaction of nevirapine and
      artemether-lumefantrine in HIV-infected patients with malaria are urgently
      needed.

PMID- 21947400
TI  - Absolute bioavailability of cis-mirincamycin and trans-mirincamycin in healthy
      rhesus monkeys and ex vivo antimalarial activity against Plasmodium falciparum.
AB  - The pharmacokinetics, oral bioavailability, and ex vivo antimalarial activity of
      mirincamycin isomers in a healthy rhesus monkey model were assessed to support
      lead optimization of novel nonhemolytic drugs for radical cure and causal
      prophylaxis of malaria. Fourteen male rhesus monkeys were randomized to four
      groups, which included cis and trans isomers by the oral and intravenous routes,
      with vehicle-only controls for each dosing route. Concentration-time data were
      collected for 7 days and were analyzed by noncompartmental analysis. cis
      Mirincamycin had an absolute oral bioavailability of 13.6%, which was slightly
      higher than that of trans-mirincamycin (11.7%), but this difference was not
      statistically significant. There was a statistically significant difference
      between the area under the concentration-time curve from zero to 48 h (AUC(0-48))
      of cis-mirincamycin and that of trans-mirincamycin after oral dosing. When
      cultured in vitro with the W2 clone of Plasmodium falciparum, the 50% inhibitory
      concentrations for cis-mirincamycin, trans-mirincamycin, and dihydroartemisinin
      were 11,300, 12,300, and 2.30 nM, respectively. However, when dosed primate
      plasma was cultured ex vivo against the W2 clone, both isomers had much greater
      relative potencies than their in vitro activities relative to results for
      dihydroartemisinin, an increase of approximately 100-fold for the cis isomer and
      150-fold for the trans isomer. Further, oral ex vivo activity was significantly
      higher than intravenous activity for both isomers, particularly during the first
      90 min following dosing, suggesting the first-pass formation of one or more
      metabolites with blood-stage antimalarial activity. Identification of the
      metabolic pathways and metabolites may help to further delineate the properties
      of this class of drugs with previously demonstrated liver-stage antimalarial
      activity.

PMID- 21947401
TI  - Digallate dimers of (-)-epigallocatechin gallate inactivate herpes simplex virus.
AB  - Topical microbicides are potentially an alternative method to vaccines for
      reducing the spread of herpes simplex virus (HSV). We have previously shown (S.
      Liu et al., Biochim. Biophys. Acta 1723:270-281, 2005) that the catechin (-)
      epigallocatechin gallate (EGCG) inactivates HSV at neutral pH; however, to
      function in the female genital tract EGCG must also be effective at acidic pH.
      EGCG inactivated HSV-1 and HSV-2 at pH 8.0 by 3 log(10) to 4 log(10) but was
      ineffective at pH 5.7. The EGCG digallate dimers theasinensin A, P2, and
      theaflavin-3,3'-digallate (TF-3) inactivated both viruses by 3 log(10) to 4
      log(10) at pH 5.7 and as much as 5 log(10) at pH 8.0. TF-3 inactivated HSV-1 and
      HSV-2 by 4 to 5 log(10) in the pH range of 4.0 to 5.7. Dimers with one gallate
      moiety had antiviral activity intermediate between the activities of EGCG and
      digallate dimers. Confocal and electron microscopy showed that theasinensin A did
      not damage Vero cells. All EGCG dimers inactivated enveloped viruses with class
      I, class II, and class III (HSV-1, HSV-2) fusion proteins more effectively than
      did monomeric EGCG. EGCG had no activity against the nonenveloped viruses tested,
      but TF-3 reduced the titer of 4 of 5 nonenveloped viruses by ?2 to 3.5 log(10).
      Results also showed that HSV-1 glycoprotein B (gB) was aggregated more rapidly by
      theasinensin A than EGCG, which, when taken together with the nonenveloped virus
      data, suggests that dimers may inhibit the function of viral proteins required
      for infectivity. Digallate dimers of EGCG appear to have excellent potential as
      microbicidal agents against HSV at acidic and neutral pHs.

PMID- 21947402
TI  - Correlation of susceptibility of Cryptococcus neoformans to amphotericin B with
      clinical outcome.
AB  - Testing of Cryptococcus neoformans for susceptibility to antifungal drugs by
      standard microtiter methods has not been shown to correlate with clinical
      outcomes. This report describes a modified quantitative broth macrodilution
      susceptibility method showing a correlation with both the patient's quantitative
      biological response in the cerebrospinal fluid (CSF) and the survival of 85
      patients treated with amphotericin B (AMB). The Spearman rank correlation between
      the quantitative in vitro measure of susceptibility and the quantitative measure
      of the number of organisms in the patient's CSF was 0.37 (P < 0.01; 95%
      confidence interval [95% CI], 0.20, 0.60) for the first susceptibility test
      replicate and 0.46 (P < 0.001; 95% CI, 0.21, 0.62) for the second susceptibility
      test replicate. The median in vitro estimated response (defined as the fungal
      burden after AMB treatment) at 1.5 mg/liter AMB for patients alive at day 14 was
      5 CFU (95% CI, 3, 8), compared to 57 CFU (95% CI, 4, 832) for those who died
      before day 14. These exploratory results suggest that patients whose isolates
      show a quantitative in vitro susceptibility response below 10 CFU/ml were more
      likely to survive beyond day 14.

PMID- 21947403
TI  - Analysis of genes encoding penicillin-binding proteins in clinical isolates of
      Acinetobacter baumannii.
AB  - There is limited information on the role of penicillin-binding proteins (PBPs) in
      the resistance of Acinetobacter baumannii to beta-lactams. This study presents an
      analysis of the allelic variations of PBP genes in A. baumannii isolates. Twenty
      six A. baumannii clinical isolates (susceptible or resistant to carbapenems) from
      three teaching hospitals in Spain were included. The antimicrobial susceptibility
      profile, clonal pattern, and genomic species identification were also evaluated.
      Based on the six complete genomes of A. baumannii, the PBP genes were identified,
      and primers were designed for each gene. The nucleotide sequences of the genes
      identified that encode PBPs and the corresponding amino acid sequences were
      compared with those of ATCC 17978. Seven PBP genes and one monofunctional
      transglycosylase (MGT) gene were identified in the six genomes, encoding (i) four
      high-molecular-mass proteins (two of class A, PBP1a [ponA] and PBP1b [mrcB], and
      two of class B, PBP2 [pbpA or mrdA] and PBP3 [ftsI]), (ii) three low-molecular
      mass proteins (two of type 5, PBP5/6 [dacC] and PBP6b [dacD], and one of type 7
      (PBP7/8 [pbpG]), and (iii) a monofunctional enzyme (MtgA [mtgA]). Hot spot
      mutation regions were observed, although most of the allelic changes found
      translated into silent mutations. The amino acid consensus sequences
      corresponding to the PBP genes in the genomes and the clinical isolates were
      highly conserved. The changes found in amino acid sequences were associated with
      concrete clonal patterns but were not directly related to susceptibility or
      resistance to beta-lactams. An insertion sequence disrupting the gene encoding
      PBP6b was identified in an endemic carbapenem-resistant clone in one of the
      participant hospitals.

PMID- 21947404
TI  - New role of the disulfide stress effector YjbH in beta-lactam susceptibility of
      Staphylococcus aureus.
AB  - Staphylococcus aureus is exposed to multiple antimicrobial compounds, including
      oxidative burst products and antibiotics. The various mechanisms and regulatory
      pathways governing susceptibility or resistance are complex and only
      superficially understood. Bacillus subtilis recently has been shown to control
      disulfide stress responses by the thioredoxin-related YjbH protein, which binds
      to the transcriptional regulator Spx and controls its degradation via the
      proteasome-like ClpXP protease. We show that the S. aureus YjbH homolog has a
      role in susceptibility to the disulfide stress-inducing agent diamide that is
      similar to that in B. subtilis, and we demonstrate that the four cysteine
      residues in YjbH are required for this activity. In addition, the inactivation of
      YjbH led to moderate resistance to oxacillin and other beta-lactam antibiotics,
      and this phenotypic change was associated with higher penicillin-binding protein
      4 levels and increased peptidoglycan cross-linking. Of note, the impact of YjbH
      on beta-lactam susceptibility still was observed when the four cysteines of YjbH
      were mutated, indicating that the roles of YjbH in disulfide stress and beta
      lactam resistance rely on different types of interactions. These data suggest
      that the ClpXP adaptor YjbH has more target proteins than previously thought, and
      that oxidative burst and beta-lactam resistance mechanisms of S. aureus are
      closely linked.

PMID- 21947405
TI  - Right ventricular outpouching associated with a ventricular septal defect: case
      report.

PMID- 21947406
TI  - Neural control of arterial pressure variability in the neuromuscularly blocked
      rat.
AB  - The baroreflexes stabilize moment-to-moment arterial pressure. Sinoaortic
      denervation (SAD) of the baroreflexes results in a large increase in arterial
      pressure variability (APV) across various species. Due to an incomplete
      understanding of the nonlinear interactions between central and peripheral
      systems, the major source of APV remains controversial. While some studies
      suggested that the variability is endogenous to the central nervous system (CNS),
      others argued that peripheral influences may be the main source. For decades,
      abnormal cardiovascular variability has been associated with a number of
      cardiovascular diseases including hypertension, heart failure, and stroke.
      Delineating mechanisms of the APV is critical for the improvement of current
      strategies that use APV as a clinical tool for the diagnosis and prognosis of
      cardiovascular diseases. In this study, with a unique chronic neuromuscularly
      blocked (NMB) rat preparation that largely constrains peripheral influences, we
      determined the CNS contribution to the post-SAD APV. First, we confirmed that SAD
      significantly increased APV in the NMB rat, then demonstrated that post-SAD
      ganglionic blockade substantially reduced APV, and subsequent intravenous
      infusions of phenylephrine and epinephrine (in presence of ganglionic blockade)
      only slightly increased APV. These data suggest that the CNS is an important
      source, and skeletal activity, thermal challenges or other forms of peripherally
      generated cardiovascular stress are not required for the post-SAD APV. In
      addition, we showed that bilateral aortic denervation produced a larger increase
      in APV than bilateral carotid sinus denervation, suggesting that the aortic
      baroreflex plays a more dominant role in the control of APV than the carotid
      sinus.

PMID- 21947407
TI  - The role of aerobic fitness and exercise intensity on endurance performance in
      uncompensable heat stress conditions.
AB  - The aim of this study was to examine the influence of aerobic fitness and
      exercise intensity on the development of thermal and cardiovascular strain in
      uncompensable heat stress conditions. In three separate trials, eight aerobically
      trained and eight untrained subjects cycled to exhaustion at 60% (H60%) and 75%
      (H75%) of maximal oxygen uptake [Formula: see text] in 40 degrees C conditions,
      and for 60 min at 60% [Formula: see text] in 18 degrees C conditions (CON).
      Training status had no influence on time to exhaustion between trained (61 +/- 10
      and 31 +/- 9 min) and untrained (58 +/- 12 and 26 +/- 10 min) subjects (H60% and
      H75%, respectively). Rectal temperature at exhaustion was also not significantly
      different between trained (39.8 +/- 0.3, 39.3 +/- 0.6 and 38.2 +/- 0.3 degrees C)
      and untrained (39.4 +/- 0.5, 38.8 +/- 0.5 and 38.2 +/- 0.4 degrees C) subjects,
      but was different between trials (H60%, H75% and CON, respectively; P < 0.01).
      However, because exercise was terminated on reaching the ethics approved rectal
      temperature limit in four trained subjects in the H60% trial and two in the H75%
      trial, it is speculated that increased rectal temperature may have further
      occurred in this cohort. Nonetheless, exhaustion occurred >96% of maximum heart
      rate in both cohorts and was accompanied by significant declines in stroke volume
      (15-26%), cardiac output (5-10%) and mean arterial pressure (9-13%) (P < 0.05).
      The increase in cardiovascular strain appears to represent the foremost factor
      precipitating fatigue during moderate and high intensity aerobic exercise in the
      heat in both trained and untrained subjects.

PMID- 21947408
TI  - Development of a perceptual hyperthermia index to evaluate heat strain during
      treadmill exercise.
AB  - Fire suppression and rescue is a physiologically demanding occupation due to
      extreme external heat as well as the physical and thermal burden of the
      protective garments. These conditions challenge body temperature homeostasis and
      results in heat stress. Accurate field assessment of core temperature is complex
      and unreliable. The present investigation developed a perceptually based
      hyperthermia metric to measure physiologic exertional heat strain during
      treadmill exercise. Sixty-five (28.9 +/- 6.8 years) female (n = 11) and male (n =
      54) firefighters and non-firefighting volunteers participated in four related
      exertional heat stress investigations performing treadmill exercise in a heated
      room while wearing thermal protective clothing. Body core temperature, perceived
      exertion, and thermal sensation were assessed at baseline, 20-mins exercise, and
      at termination. Perceived exertion increased from baseline (0.24 +/- 0.42) to
      termination (7.43 +/- 1.86). Thermal sensation increased from baseline (1.78 +/-
      0.77) to termination (4.50 +/- 0.68). Perceived exertion and thermal sensation
      were measured concurrently with body core temperature to develop a two
      dimensional graphical representation of three exertional heat strain zones
      representative of a range of mean body core temperature responses such that low
      risk (green) incorporated 36.0-37.4 degrees C, moderate risk (yellow)
      incorporated 37.5-37.9 degrees C, and high risk (red) incorporated 38.0 to
      greater than 40.5 degrees C. The perceptual hyperthermia index (PHI) may provide
      a quick and easy momentary assessment of the level of risk for exertional heat
      stress for firefighters engaged in fire suppression that may be beneficial in
      high-risk environments that threaten the lives of firefighters.

PMID- 21947409
TI  - Effect of carrying a weighted backpack on lung mechanics during treadmill walking
      in healthy men.
AB  - Weighted backpacks are used extensively in recreational and occupational
      settings, yet their effects on lung mechanics during acute exercise is poorly
      understood. The purpose of this study was to determine the effects of different
      backpack weights on lung mechanics and breathing patterns during treadmill
      walking. Subjects (n = 7, age = 28 +/- 6 years), completed two 2.5-min exercise
      stages for each backpack condition [no backpack (NP), an un-weighted backpack
      (NW) or a backpack weighing 15, 25 or 35 kg]. A maximal expiratory flow volume
      curve was generated for each backpack condition and an oesophageal balloon
      catheter was used to estimate pleural pressure. The 15, 25 and 35 kg backpacks
      caused a 3, 5 and 8% (P < 0.05) reduction in forced vital capacity compared with
      the NP condition, respectively. For the same exercise stage, the power of
      breathing (POB) requirement was higher in the 35 kg backpack compared to NP (32
      +/- 4.3 vs. 88 +/- 9.0 J min(-1), P < 0.05; respectively). Independent of changes
      in minute ventilation, end-expiratory lung volume decreased as backpack weight
      increased. As backpack weight increased, there was a concomitant decline in
      calculated maximal ventilation, a rise in minute ventilation, and a resultant
      greater utilization of maximal available ventilation. In conclusion, wearing a
      weighted backpack during an acute bout of exercise altered operational lung
      volumes; however, adaptive changes in breathing mechanics may have minimized
      changes in the required POB such that at an iso-ventilation, wearing a backpack
      weighing up to 35 kg does not increase the POB requirement.

PMID- 21947410
TI  - Prevention of ovarian damage and infertility in young female cancer patients
      awaiting chemotherapy--clinical approach and unsolved issues.
AB  - Great advances in the oncological therapy of childhood and adolescent cancer
      patients lead to an increase of young cancer survivors with a normal expectancy
      of life. The aggressive chemotherapy and/or radiation often compromises endocrine
      function with consecutive menopausal symptoms and sterility. Recently, new
      approaches were developed to preserve fertility with different methods to restore
      the ovarian function. The present review gives an overview of the current
      possibilities, which may be offered to these young cancer patients, as well as
      the chances of success and risks and the unsolved issues in special situations.

PMID- 21947411
TI  - Challenging the perceptions of cancer service provision for the disadvantaged:
      evaluating utilisation of cancer support services in Western Australia.
AB  - PURPOSE: The main aim of the study was to evaluate the distributive utilisation
      of services provided by the Cancer Council of Western Australia according to age,
      social disadvantage and geographic location. Results were used to determine if
      social justice principles in terms of service provision were upheld. METHODS:
      Cross-sectional study design to evaluate utilisation of cancer support services
      over a 12-week period in 2007 using administrative records. Service utilisation
      incidence rates (population information obtained from de-identified cancer
      registry data) and incidence rate ratios were calculated by gender, age group,
      cancer type, socioeconomic status and location. RESULTS: The Information services
      (52%, n = 4,932) were the most popular Cancer Council of Western Australia (CCWA)
      services followed by Emotional Support services (21%, n = 2,045). All CCWA
      services were more likely to be accessed by those with a lower socioeconomic
      status, except for Clinical Services. The rate of utilisation for patients with
      cancer in the 65+ years age group was found to be under-serviced relative to the
      40-64 years age group. CONCLUSIONS: Overall, the study has shown that CCWA
      services are not provided uniformly (horizontal equity) across strata of socio
      economic status. Given that the prevalence of cancer generally increases with
      socio-economic advantage, the findings were notable in regard to one particular
      outcome. Results for age indicate that there may be some underlying accessibility
      issues for the aged population. The findings are consistent with current
      literature highlighting issues of disadvantage in regard to the ability of
      elderly persons with cancer to access services and support.

PMID- 21947412
TI  - Physical activity preferences in a population-based sample of kidney cancer
      survivors.
AB  - PURPOSE: Physical activity (PA) improves quality of life in kidney cancer
      survivors (KCS), but PA participation rates are low. Behavior change
      interventions to increase PA in KCS should take into account PA preferences. The
      purpose of this study was to identify the PA preferences of KCS and determine any
      associations with selected demographic and medical variables. METHODS: All 1,985
      KCS diagnosed between 1996 and 2010 identified through a Canadian provincial
      registry in Alberta, Canada were mailed a survey that consisted of the Godin
      Leisure-Time Exercise Questionnaire and various PA preference variables. Standard
      demographic and medical variables were also collected. RESULTS: Completed surveys
      were received from 703 of 1,654 (43%) eligible KCS. Over 80% of KCS felt they
      were able or may be able to participate in a PA program designed for KCS and over
      70% were interested or may be interested in doing so. The most common PA
      preferences were to receive PA information from a fitness expert at a cancer
      center (55.7%), receive information via print material (50.0%), start a PA
      program after treatment (36.5%), exercise with a spouse (39.6%), exercise at home
      (52.0%), do moderate-intensity PA (58.4%), and walk in both the summer (69.4%)
      and winter (48.2%). Chi-square analyses uncovered that age, sex, and current PA
      were the personal variables most consistently associated with PA preferences.
      CONCLUSION: The majority of KCS expressed an interest in doing a PA program and
      important preferences were identified. These preferences may be used to inform PA
      interventions to enhance motivation and adherence in KCS.

PMID- 21947413
TI  - Controlled synthesis of magnetic iron oxides@SnO2 quasi-hollow core-shell
      heterostructures: formation mechanism, and enhanced photocatalytic activity.
AB  - Iron oxide/SnO(2) magnetic semiconductor core-shell heterostructures with high
      purity were synthesized by a low-cost, surfactant-free and environmentally
      friendly hydrothermal strategy via a seed-mediated method. The morphology and
      structure of the hybrid nanostructures were characterized by means of high
      resolution transmission electron microscopy and X-ray diffraction. The morphology
      evolution investigations reveal that the Kirkendall effect directs the diffusion
      and causes the formation of iron oxide/SnO(2) quasi-hollow particles.
      Significantly, the as-obtained iron oxides/SnO(2) core-shell heterostructures
      exhibited enhanced visible light or UV photocatalytic abilities, remarkably
      superior to as-used alpha-Fe(2)O(3) seeds and commercial SnO(2) products, mainly
      owing to the effective electron hole separation at the iron oxides/SnO(2)
      interfaces.

PMID- 21947414
TI  - Thermophysical and biological responses of gold nanoparticle laser heating.
AB  - A compelling vision in nanomedicine is the use of self directed nanoparticles
      that can accumulate in areas of disease to perform designed functions, such as
      molecular delivery or destruction, endosomal release of genes or siRNA, and
      selective cell or tumor destruction with nano to macroscale spatiotemporal
      control and precision. These functions are increasingly achieved by gold
      nanoparticles (GNPs, such as sphere, shell or rod) that can be activated with a
      laser "switch". A defining aspect of this "switch" is GNP absorption of laser
      light and the ensuing heat generation and temperature change that can be confined
      or propagated through multiple scales from the nanoparticle surface up through
      bulk biological cells and tissues. In this critical review, we discuss the
      fundamental mechanisms of laser GNP heat generation, the measurement and
      modelling of the ensuing thermal response, and a number of the evolving
      biological applications dependent on this new technology (181 references).

PMID- 21947416
TI  - Crystal structure and conformational analysis of s-cis
      (acetylacetonato)(ethylenediamine-N,N'-diacetato)-chromium(III): development of
      vibrationally optimized force field (VOFF).
AB  - The crystal structure of [Cr(edda)(acac)] (edda = ethylediamine-N,N'-diacetate;
      acac = acetylacetonato) has been determined by a single crystal X-ray diffraction
      study at 150 K. The chromium ion is in a distorted octahedral environment
      coordinated by two N and two O atoms of chelating edda and two O atoms of acac,
      resulting in s-cis configuration. The complex crystallizes in the space group
      P2(1)/c of the monoclinic system in a cell of dimensions a = 10.2588(9), b =
      15.801(3), c = 8.7015(11) A, beta =101.201(9) degrees  and Z = 4. The mean Cr
      N(edda), Cr-O(edda) and Cr-O(acac) bond distances are 2.0829(14), 1.9678(11) and
      1.9477(11) A while the angles O-Cr-O of edda and O-Cr-O of acac are 171.47(5) and
      92.72(5) degrees , respectively. The crystal structure is stabilized by N-H...O
      hydrogen bonds linking [Cr(edda)(acac)] molecules in distinct linear strands. The
      visible electronic and IR spectroscopic properties are also discussed. An
      improved, physically more realistic force field, Vibrationally Optimized Force
      Field (VOFF), capable of reproducing structural and vibrational properties of
      [Cr(edda)(acac)] was developed and its transferability demonstrated on selected
      chromium(III) complexes with similar ligands.

PMID- 21947415
TI  - C-peptide reduces pro-inflammatory cytokine secretion in LPS-stimulated U937
      monocytes in condition of hyperglycemia.
AB  - OBJECTIVE: We investigated C-peptide effects on inflammatory cytokine release and
      adhesion of monocytes exposed to high glucose and lipopolysaccharide (LPS) in
      vitro. MATERIALS AND METHODS: Monocytic cells (U-937) were cultured in the
      presence of 30 mmol/L glucose and stimulated with 0.5 ng/MUL LPS in the presence
      or absence of C-peptide (1 MUmol/L) for 24 h to induce inflammatory cytokine
      secretion. Adhesion of U-937 monocytes to human aortic endothelial cells (HAEC)
      was also studied in the presence or absence of C-peptide. Concentrations of IL-6,
      IL-8, macrophage inflammatory protein(MIP)-1alpha, and MIP-1beta in supernatants
      from LPS-stimulated U-937 monocytes were assessed by Luminex. To gain insights
      into potential intracellular signaling pathways affected by C-peptide, we
      investigated nuclear translocation of nuclear factor(NF)-kappaB p65/p50 subunits
      by western blot in LPS-treated U-937 cells. The effect of C-peptide on LPS
      induced phosphorylation of the cytoplasmic protein IkappaB-alpha was also
      investigated by immunoblotting. RESULTS: Addition of C-peptide significantly
      reduced cytokine secretion from LPS-stimulated U-937 monocytes. Adhesion of U-937
      cells to HAEC was also significantly reduced by C-peptide. These effects were
      accompanied by reduced NF-kappaB p65/p50 nuclear translocation and decreased
      phosphorylation of IkappaB-alpha. CONCLUSIONS: We conclude that, in conditions of
      hyperglycemia, C-peptide reduces monocytes activation via inhibition of the NF
      kappaB pathway.

PMID- 21947417
TI  - Investigating the electronic properties of silicon nanosheets by first-principles
      calculations.
AB  - Using first-principles total energy calculations within the density functional
      theory (DFT), we investigated the electronic and structural properties of
      graphene-like silicon sheets. Our studies were performed using the LSDA (PWC) and
      GGS (PBE) approaches. Two configurations were explored: one corresponding to a
      defect-free layer (h-Si), and the other to a layer with defects (d-Si), both of
      which were in the armchair geometry. These sheets contained clusters of the
      C(n)H(m) type. We also investigated the effects of doping with group IV-A
      elements. Structural stability was studied by only considering positive vibration
      frequencies. Results showed that both h-Si and d-Si present a corrugated
      structure with concavity. h-Si sheets were found to be ionic (D.M. = 0.33 Debye)
      with an energy gap (HOMO-LUMO) of 0.77 eV in the LSDA theory and 0.76 eV in the
      GGS approach, while d-Si sheets were observed to be covalent (D.M. = 2.78 D), and
      exhibited semimetallic electronic behavior (HOMO-LUMO gap = 0.32 eV within the
      LSDA theory and 0.33 eV within the GGS approach). d-Si sheets doped with one
      carbon or one germanium preserved the polarity of the undoped d-Si sheets, as
      well as their semimetallic electronic behavior. However, when the sheets were
      doped with two C or two Ge atoms, or with one of each atom (to give
      Si(52)CGeH(18)), they retained the semimetallic behavior, but they changed from
      having ionic character to covalent character.

PMID- 21947418
TI  - Supraclavicular flap in head and neck reconstruction: experience in 50
      consecutive patients.
AB  - The supraclavicular flap (SCF) is a fasciocutaneous flap used to cover head,
      oral, and neck region defects after tumor resection. Its main vascular supply is
      the supraclavicular artery and accompanying veins and it can be harvested as a
      vascularised pedicled flap. The SCF serves as an excellent outer skin cover as
      well as a good inner mucosal lining after oral cavity and head-neck tumor
      resections. The flap has a wide arc of rotation and matches the skin colour and
      texture of the face and neck. Between March 2006 and March 2011, the pedicled
      supraclavicular flap was used for reconstruction in 50 consecutive patients after
      head and neck tumor resections and certain benign conditions in a tertiary
      university hospital setting. The flaps were tunnelized under the neck skin to
      cover the external cervicofacial defects or passed medial to the mandible to give
      an inner epithelial lining after the oral cavity and oropharyngeal tumor
      excision. Forty-four of the 50 patients had 100% flap survival with excellent
      wound healing. All the flaps were harvested in less than 1 h. There were four
      cases of distal tip desquamation and two patients had complete flap necrosis.
      Distal flap desquamation was observed in SCFs used for resurfacing the external
      skin defects after oral cavity tumor ablation and needed only conservative
      treatment measures. Total flap failure was encountered in two patients who had
      failed in previous chemoradiotherapy for squamous cell cancer of the floor of
      mouth and tonsil, respectively, and the SCF was used in mucosal defect closure
      after tumor ablation. The benefits of a pedicled fasciocutaneous supraclavicular
      flap are clear; it is thin, reliable, easy, and quick to harvest. In head, face
      and neck reconstructions, it is a good alternative to free fasciocutaneous flaps,
      regional pedicled myocutaneous flaps, and the deltopectoral flap.

PMID- 21947420
TI  - Genome-wide association study identifies HMGN3 locus for spine bone size
      variation in Chinese.
AB  - Bone size (BS) is one of the major risk factors for osteoporotic fractures. BS
      variation is genetically determined to a substantial degree with heritability
      over 50%, but specific genes underlying variation of BS are still largely
      unknown. To identify specific genes for BS in Chinese, initial genome-wide
      association scan (GWAS) study and follow-up replication study were performed. In
      initial GWAS study, a group of 12 contiguous single-nucleotide polymorphism
      (SNP)s, which span a region of ~25 kb and locate at the upstream of HMGN3 gene
      (high-mobility group nucleosomal binding domain 3), achieved moderate association
      signals for spine BS, with P values ranging from 6.2E-05 to 1.8E-06. In the
      follow-up replication study, eight of the 12 SNPs were detected suggestive
      replicate associations with BS in 1,728 unrelated female Caucasians, which have
      well-known differences from Chinese in ethnic genetic background. The SNPs in the
      region of HMGN3 gene formed a tightly combined haplotype block in both Chinese
      and Caucasians. The results suggest that the genomic region containing HMGN3 gene
      may be associated with spine BS in Chinese.

PMID- 21947419
TI  - SLC39A2 and FSIP1 polymorphisms as potential modifiers of arsenic-related bladder
      cancer.
AB  - Arsenic is a carcinogen that contaminates drinking water worldwide. Accumulating
      evidence suggests that both exposure and genetic factors may influence
      susceptibility to arsenic-induced malignancies. We sought to identify novel
      susceptibility loci for arsenic-related bladder cancer in a US population with
      low to moderate drinking water levels of arsenic. We first screened a subset of
      bladder cancer cases using a panel of approximately 10,000 non-synonymous single
      nucleotide polymorphisms (SNPs). Top ranking hits on the SNP array then were
      considered for further analysis in our population-based case-control study (n =
      832 cases and 1,191 controls). SNPs in the fibrous sheath interacting protein 1
      (FSIP1) gene (rs10152640) and the solute carrier family 39, member 2 (SLC39A2) in
      the ZIP gene family of metal transporters (rs2234636) were detected as potential
      hits in the initial scan and validated in the full case-control study. The
      adjusted odds ratio (OR) for the FSIP1 polymorphism was 2.57 [95% confidence
      interval (CI) 1.13, 5.85] for heterozygote variants (AG) and 12.20 (95% CI 2.51,
      59.30) for homozygote variants (GG) compared to homozygote wild types (AA) in the
      high arsenic group (greater than the 90th percentile), and unrelated in the low
      arsenic group (equal to or below the 90th percentile) (P for interaction =
      0.002). For the SLC39A2 polymorphism, the adjusted ORs were 2.96 (95% CI 1.23,
      7.15) and 2.91 (95% CI 1.00, 8.52) for heterozygote (TC) and homozygote (CC)
      variants compared to homozygote wild types (TT), respectively, and close to one
      in the low arsenic group (P for interaction = 0.03). Our findings suggest novel
      variants that may influence risk of arsenic-associated bladder cancer and those
      who may be at greatest risk from this widespread exposure.

PMID- 21947421
TI  - Synergistic antitumor activity of oridonin and arsenic trioxide on hepatocellular
      carcinoma cells.
AB  - Although arsenic trioxide (As2O3) has been successfully employed in treatment of
      patients with APL (acute promyelocytic leukemia), the sensitivity of solid tumor
      cells to this treatment was much lower than APL cells. The single agent of As2O3
      was inefficient for treatment of hepatocellular carcinoma (HCC) in phase II trial
      demonstrating that new modalities of treatment with enhanced therapeutic effect
      are needed. In this study, we showed that oridonin, a diterpenoid isolated from
      traditional Chinese medicine Rabdosia rubescences, greatly potentiated apoptosis
      induced by As2O3 in hepatocellular carcinoma cells. The synergistic pro-apoptosis
      effect of combination of these two drugs led to increase in intracellular
      reactive oxygen species (ROS) level and N-acetyl-L-cysteine (NAC), a thiol
      containing anti-oxidant, was able to completely block the effect. The combination
      treatment induced ROS-dependent decrease in mitochondrial membrane potential
      (MMP) decrease, and relocation of Bax and cytochrome C. Besides, oridonin
      dramatically increased the intracellular Ca2+ overload triggered by As2O3.
      Furthermore, the co-treatment of oridonin and As2O3 induced ROS-mediated down
      regulation of Akt and XIAP, and inhibition of NF-kappaB activation. The two drug
      combination enhanced tumor suppression activity in murine HCC model compared with
      single agent treatment in vivo. These findings demonstrate that oridonin can
      sensitize hepatocellular carcinoma cells to As2O3 treatment and will facilitate
      the optimization of As2O3 therapy for HCC patients.

PMID- 21947422
TI  - Involvement of abscisic acid in ozone-induced puerarin production of Pueraria
      thomsnii Benth. suspension cell cultures.
AB  - Exposure to ozone induced a rapid increase in the levels of the sesquiterpene
      phytohormone abscisic acid (ABA) and the isoflavone puerarin in suspension cell
      cultures of Pueraria thomsnii Benth. The observed increases in ABA and puerarin
      were dependent on the concentration of ozone applied to P. thomsnii cell
      cultures. In order to examine the role of ABA in ozone-induced puerarin
      production, cell suspensions were pretreated with the ABA biosynthetic inhibitor
      fluridone. Following ozone exposure, fluridone treatment suppressed ABA
      accumulation suggesting ABA was normally synthesized de novo through the
      carotenoid pathway. Fluridone also blocked ozone-induced puerarin production,
      which could be reversed through application of exogenous ABA. However, in the
      absence of ozone, ABA itself had no effect on puerarin accumulation in the
      suspension cells. Taken together, the data indicate that ozone is an efficient
      elicitor of puerarin production and may be particularly applicable for improving
      puerarin production in plant cell cultures. Furthermore, we demonstrate that ABA
      is one factor associated with ozone-induced puerarin production in P. thomsnii
      cell cultures.

PMID- 21947423
TI  - Environmental pollutants and beta cell function: relevance for type 1 and
      gestational diabetes.

PMID- 21947424
TI  - Long-term visual outcome and aneurysm obliteration rate for very large and giant
      ophthalmic segment aneurysms: assessment of surgical treatment.
AB  - BACKGROUND: Standard endovascular therapy has shown little success in treatment
      of very large and giant ophthalmic segment aneurysms. We hypothesize that
      surgical treatment of these aneurysms yields better results in terms of visual
      function and aneurysm obliteration. METHODS: The Toronto Brain Vascular
      Malformation Study Group database was analyzed to retrieve patients treated
      surgically for very large (>15 mm) and giant aneurysms of the ophthalmic segment
      of the carotid artery. Preoperative data and postoperative long-term outcomes
      with specific consideration for visual function and aneurysm obliteration were
      evaluated. RESULTS: Of the 257 patients with ophthalmic and paraophthalmic
      aneurysms, 38 patients had very large or giant aneurysms. Twenty-one underwent
      surgical treatment; 19 had direct clipping; 1 had trapping, and 1 underwent
      trapping and bypass. Fifteen patients had unruptured and six had ruptured
      aneurysms. The mean follow-up period was 88 months. Six (28%) aneurysms had a
      small residual neck remnant. Of the 12 patients with documented preoperative
      visual deficit, 9 (75%) improved, 2 (16%) remained stable, and 1 (8%) worsened.
      Two patients had mild to moderate new visual deficit. Thus, the surgery-related
      visual complications were 14%. Eighteen patients (86%) had a good or excellent
      outcome (GOS IV and V). Presentation with prior visual deficit and poor
      neurological function were predictors of worse visual and clinical outcome,
      respectively (P = 0.02 and 0.01). CONCLUSIONS: There is considerable surgery
      related risk for optic pathways during treatment of very large and giant
      ophthalmic segment aneurysms. Surgery, however, seems to be the treatment of
      choice in terms of overall visual outcome and aneurysm obliteration as compared
      to the current endovascular results in this subset of patients.

PMID- 21947425
TI  - En-bloc craniotomy for the pre-sigmoid infra- and supratentorial approach:
      technical note.
AB  - INTRODUCTION: The combined supra-infratentorial approach as described some 30
      years ago is to date considered a standard procedure for skull base procedures.
      Several variants have been devised, including preservation of the mastoid
      process. We herein present the cosmetically most sophisticated and fastest
      solution. OBJECTIVES: The authors describe an en bloc supra- and infratentorial
      pre-sigmoid combined approach. This variant of surgical technique involves a one
      piece bone flap (temporal-suboccipital-mastoideal flap). We present another
      variant of craniotomy for the combined supra- and infratentorial pre-sigmoid
      approach that preserves the mastoid process and thus appears to be cosmetically
      much more acceptable. MATERIALS AND METHODS: Eight dry cadaveric skulls were used
      to develop an ideal one-piece excision of the cranial vault across the transverse
      sinus, including portions of the mastoid. Our aim was that no further drilling of
      the basal skull was needed. The procedure thereafter was practiced on a fresh
      prepared cadaveric specimen where its feasibility was again confirmed and was
      then applied to a patient suffering from a huge petroclival meningioma. It was
      very well tolerated and produced an excellent long-term cosmetic result.
      DISCUSSION: The combined supra- and infratentorial pre-sigmoid approach offers
      the possibility of resecting complex petroclival lesions. The variant presented
      herein is less time consuming than previously described methods and probably
      offers the best possible cosmetic result. CONCLUSION: The en-bloc cranioplastic
      approach with preservation of the mastoid process is a new, interesting variant
      of a classical technique that is easy to perform and has the intention of
      achieving the best possible cosmetic result.

PMID- 21947426
TI  - Exotic species, experienced, and idealized nature.
AB  - This paper is an answer to the Caplat and Coutts forum about our previous paper
      "The need for flexibility in conservation practices: exotic species as an
      example". We precise here why we proposed to consider exotic species as well as
      indigenous species in the reconnection framework in human-modified environments.
      One argument is that consistent and understandable arguments must be used in the
      communication from scientists to the public, in order not to decrease the gap
      between science and society.

PMID- 21947427
TI  - Autoimmune hemolytic anemia in a 2-year-old child with pneumococcal pneumonia.

PMID- 21947428
TI  - Resistance exercise and aerobic exercise when paired with dietary energy
      restriction both reduce the clinical components of metabolic syndrome in
      previously physically inactive males.
AB  - The purpose of this study was to compare resistance exercise training (RT) to
      aerobic exercise training (AE) on the clinical risk factors for metabolic
      syndrome (MetSyn) in physically inactive overweight males (age 27-48 years).
      Subjects with at least one risk factor for MetSyn performed RT (n = 13, age 35.1
      +/- 4.7 years, BMI 31.2 +/- 2.7 kg/m(2)) or AE (n = 9, age 37.6 +/- 4.9 years,
      BMI, 31.2 +/- 3.2 kg/m(2)) for 6 months. Training frequency and exercise session
      duration were equal and by 3 months the subjects exercised 4 day/week for 45
      min/session. Blood lipids and glucose, waist circumference, and mean arterial
      blood pressure (MAP) were measured at 0, 3, and 6 months. A MetSyn z score was
      calculated for each subject from triglycerides, HDL cholesterol, fasting glucose,
      waist circumference, and MAP. Statistical significance was set at p <= 0.05. No
      significant differences existed between RT and AE groups at 0 month. AE showed a
      significant reduction in MetSyn z score from 0 (0.91 +/- 3.57) to 6 months (-1.35
      +/- 2.95), while RT approached significance (p = 0.07) from 0 (0.09 +/- 2.62) to
      6 months (-1.30 +/- 2.22). Triglycerides (mmol/L) significantly decreased in AE
      from 0 (1.93 +/- 0.90) to 6 months (1.41 +/- 0.70). Waist circumference (cm)
      significantly decreased in AE from 0 (106.8 +/- 7.3) to 6 months (101.2 +/- 6.5),
      and in RT from 0 (108.4 +/- 9.0) to 6 months (105.7 +/- 7.0). MAP (mmHg)
      decreased in RT from 0 (93.8 +/- 5.8) to 6 months (87.5 +/- 6.1) and in AE from 0
      (97.6 +/- 7.0) to 6 months (91.3 +/- 6.8). With equal training frequency and
      exercise session duration, both RT and AE training, when paired with energy
      restriction improve the clinical risk factor profile for MetSyn.

PMID- 21947429
TI  - Microbial community changes elicited by exposure to cyanobacterial
      allelochemicals.
AB  - An increasing body of evidence points out that allelopathy may be an important
      process shaping microbial communities in aquatic ecosystems. Cyanobacteria have
      well-documented allelopathic properties, mainly derived from the evaluation of
      the activity of allelopathic extracts or pure compounds towards monocultures of
      selected target microorganisms. Consequently, little is known regarding the
      community dynamics of microorganisms associated with allelopathic interactions.
      In this laboratory-based study, a Microcystis spp.-dominated microbial community
      from a freshwater lake was exposed, for 15 days, to exudates from the
      cyanobacterium Oscillatoria sp. strain LEGE 05292 in laboratory conditions. This
      cyanobacterium is known to produce the allelochemicals portoamides, which were
      among the exuded compounds. The community composition was followed (by means of
      polymerase chain reaction followed by denaturing gradient gel electrophoresis and
      microscopic analyses) and compared to that of a non-exposed situation. Following
      exposure, clear differences in the community structure were observed, in
      particular for cyanobacteria and unicellular eukaryotic taxa. Interestingly,
      distinct Microcystis genotypes present in the community were differentially
      impacted by the exposure, highlighting the fine-scale dynamics elicited by the
      exudates. These results support a role for cyanobacterial allelochemicals in the
      structuring of aquatic microbial communities.

PMID- 21947431
TI  - First self-assembly study of betulinic acid, a renewable nano-sized, 6-6-6-6-5
      pentacyclic monohydroxy triterpenic acid.
AB  - Self-assembly of betulinic acid, a renewable nano-sized 6-6-6-6-5 pentacyclic
      triterpenic acid studied in twenty two organic liquids and alcohol-water mixtures
      showed that it self-assembled in all the liquids studied affording strong gels in
      nineteen organic liquids and also in alcohol-water mixtures. Optical and electron
      microscopy and atomic force microscopy studies revealed fibrillar networks having
      fibers of nano- to micro-metre cross sections and micrometre lengths.

PMID- 21947430
TI  - Microbial diversity inside pumpkins: microhabitat-specific communities display a
      high antagonistic potential against phytopathogens.
AB  - Recent and substantial yield losses of Styrian oil pumpkin (Cucurbita pepo L.
      subsp. pepo var. styriaca Greb.) are primarily caused by the ascomycetous fungus
      Didymella bryoniae but bacterial pathogens are frequently involved as well. The
      diversity of endophytic microbial communities from seeds (spermosphere), roots
      (endorhiza), flowers (anthosphere), and fruits (carposphere) of three different
      pumpkin cultivars was studied to develop a biocontrol strategy. A multiphasic
      approach combining molecular, microscopic, and cultivation techniques was applied
      to select a consortium of endophytes for biocontrol. Specific community
      structures for Pseudomonas and Bacillus, two important plant-associated genera,
      were found for each microenvironment by fingerprinting of 16S ribosomal RNA
      genes. All microenvironments were dominated by bacteria; fungi were less
      abundant. Of the 2,320 microbial isolates analyzed in dual culture assays, 165
      (7%) were tested positively for in vitro antagonism against D. bryoniae. Out of
      these, 43 isolates inhibited the growth of bacterial pumpkin pathogens
      (Pectobacterium carotovorum, Pseudomonas viridiflava, Xanthomonas cucurbitae);
      here only bacteria were selected. Microenvironment-specific antagonists were
      found, and the spermosphere and anthosphere were revealed as underexplored
      reservoirs for antagonists. In the latter, a potential role of pollen grains as
      bacterial vectors between flowers was recognized. Six broad spectrum antagonists
      selected according to their activity, genotypic diversity, and occurrence were
      evaluated under greenhouse conditions. Disease severity on pumpkins of D.
      bryoniae was significantly reduced by Pseudomonas chlororaphis treatment and by a
      combined treatment of strains (Lysobacter gummosus, P. chlororaphis,
      Paenibacillus polymyxa, and Serratia plymuthica). This result provides a
      promising prospect to biologically control pumpkin diseases.

PMID- 21947432
TI  - Rate of post-tonsillectomy hemorrhage after elective bipolar microcauterization
      of nonbleeding vessels.
AB  - The objective of this paper is to describe an extended microscopic hemostasis
      technique involving cauterization of exposed blood vessels that were not actively
      bleeding in tonsillar fossa after bipolar tonsillectomy and to assess the rate of
      post-tonsillectomy hemorrhage with this technique in children who had bipolar
      tonsillectomy. The medical records of children who underwent microscopic bipolar
      tonsillectomy with extended hemostasis between June 2008 and January 2011 were
      reviewed. Relevant history and physical examination, diagnosis, and
      characteristics of postoperative hemorrhage were recorded; 994 children (531
      males, 463 females), aged between 1 and 18 years (6 +/- 3 years), underwent
      tonsillectomy; of the 994 patients, 11 (1.1%) developed post-tonsillectomy
      hemorrhage. No primary post-tonsillectomy hemorrhage occurred. The hemorrhage was
      seen 6-13 days after the surgery. One patient had bleeding after having trauma to
      the neck on postoperative day 13. Of the 11 patients with post-tonsillectomy
      bleeding, 3 had blood clot with no active bleeding and 8 exhibited active
      bleeding after removal of blood clot. Of the 994 patients, 8 (0.8%) needed
      intervention to control active bleeding. Compared to previous studies of bipolar
      tonsillectomy, extended microscopic hemostasis achieved by cauterization of
      tonsil fossa non-bleeding blood vessels appeared to reduce bleeding rate after
      bipolar cautery tonsillectomy. The present study did not include a control arm;
      further randomized controlled studies are needed to establish the definite effect
      of extended microscopic hemostasis technique on the rate of hemorrhage rates
      after tonsillectomy techniques.

PMID- 21947433
TI  - Sinonasal involvement in sarcoidosis: a report of seven cases and review of
      literature.
AB  - Sarcoidosis is a chronic systemic disease of unknown etiology characterized by
      non-caseating inflammation involving one or more organs with predilection for
      pulmonary and upper respiratory tract involvement. It presents with a variety of
      signs and symptoms which can be generalized or focused on a single organ.
      Sinonasal involvement is reported in about 1% of cases of sarcoidosis.
      Sarcoidosis can involve both the mucosa as well as bony structures in the nose
      and the paranasal sinuses. We present seven cases of sarcoidosis with sinonasal
      involvement. Four cases presented with nasal and sinus symptoms, and the other
      three cases developed or presented with nasal and sinus symptoms after the
      diagnosis of sarcoidosis was confirmed. The nasal and sinus symptoms in these
      patients were managed by local and systemic steroids. In four patients,
      endoscopic sinus surgery was performed with good outcome. Nasal and sinus
      symptoms, differential diagnosis and the treatment are discussed.

PMID- 21947434
TI  - Use of cone beam computed tomography in otolaryngologic treatments.
AB  - Cone beam computed tomography (CBCT) allows us to evaluate 3-dimensional (3D)
      morphology of the maxillofacial skeleton and also used in dentomaxillofacial
      imaging to solve complex diagnostic and treatment planning problems such as
      craniofacial fractures, temporamandibular dysfunctions or sinus imaging. CBCT
      uses a rectangular or round 2D detector, which allows a single rotation of the
      gantry to generate a scan of the entire region of interest. Technological and
      application-specific factors such as development of compact, relatively low-cost,
      high-quality, large, flat-panel detector arrays; the availability of low-cost
      computers with processing power sufficient for cone beam image reconstruction;
      the fabrication of highly efficient radiograph tubes capable of multiple
      exposures necessary for cone beam scanning at prices lower than those currently
      used for fan beam CT; and limited volume scanning (e.g., head and neck)
      eliminating the need for subsecond gantry rotation speeds make this possible. The
      objective of this study is to review published evidence for CBCT having an
      important role in ORL treatments. We aimed to review all the available literature
      about the CBCT imagination in ORL treatments. Systematic literature search was
      performed using PubMed and Ovid. Additional literature was retrieved from
      reference lists in the articles. Systematic analysis of the literature from 1998
      to 2010 was performed. A total of 40 abstracts were evaluated independently by
      two members of the project group, and 38 articles were included in the review.

PMID- 21947435
TI  - Utility of glycated albumin for the diagnosis of diabetes mellitus in a Japanese
      population study: results from the Kyushu and Okinawa Population Study (KOPS).
AB  - AIMS/HYPOTHESIS: Glycated albumin is a measure of the mean plasma glucose
      concentration over approximately 2-3 weeks. We determined reference values for
      glycated albumin, and assessed its utility for the diagnosis of type 2 diabetes
      mellitus in the general population. METHODS: We studied 1,575 men and women (mean
      age, 49.9 years; range, 26-78 years) who participated in a periodic health
      examination in a suburban Japanese town. HbA(1c) and fasting plasma
      concentrations of glucose (FPG) and glycated albumin were measured. Participants
      with FPG >= 7.0 mmol/l or HbA(1c) >= 6.5% (48 mmol/mol) were diagnosed as having
      diabetes. In our laboratory, the glycated albumin assay had intra-assay and inter
      assay CVs of 1.1% and 1.6%, respectively. RESULTS: Glycated albumin levels were
      significantly correlated with HbA(1c) levels (r = 0.766, p < 0.001) and FPG (r =
      0.706, p < 0.001). The presence of diabetes was significantly higher in
      participants with glycated albumin levels between 15.0% and 15.9% (five of 276,
      1.81%) than in those with glycated albumin <14% (three of 672, 0.45%) (p =
      0.037), and was markedly increased in those with a glycated albumin level >16%
      (58 of 207, 28.0%). Receiver operating characteristic curve analysis indicated
      that a glycated albumin level of >=15.5% was optimal for predicting diabetes,
      with a sensitivity of 83.3% and a specificity of 83.3%.
      CONCLUSIONS/INTERPRETATION: There is merit to further investigating the potential
      for glycated albumin to be used as an alternative measure of dysglycaemia for
      future research and clinical practice.

PMID- 21947437
TI  - A flow-through microarray cell for the online SERS detection of antibody-captured
      E. coli bacteria.
AB  - We present an immunoassay microarray flow-through system for the surface-enhanced
      Raman scattering (SERS) analysis of bacteria. The system has been constructed to
      support and automatize the nondestructive in situ analysis of different
      microorganisms in aqueous environment. After the immobilization of the desired
      antibodies to an activated PEG-coated surface, the chip is placed into the flow
      cell which is then flushed with the contaminated sample. Finally, colloidal metal
      nanoparticles are added and the cells are detected label-free by SERS. Here, we
      introduce the successful imaging of single microorganisms in the flow cell as
      well as the quantification of microorganisms in water by SERS mapping with a
      linear range between 4.3 * 10(3) to 4.3 * 10(5) cells/mL. The method has
      potential for routine application, e.g. for drinking water control.

PMID- 21947436
TI  - Alternating temperature breaks dormancy in leafy spurge seeds and impacts
      signaling networks associated with HY5.
AB  - Non-after-ripened seeds of the herbaceous perennial weed leafy spurge do not
      germinate when imbibed at a constant temperature (C), but transfer to an
      alternating temperature (A) induced germination. Changes in the transcriptome of
      seeds during 1 and 3 days of alternating temperature and germinated seeds were
      compared with seeds incubated at constant temperature. Statistical analysis
      revealed that 597, 1,491, and 1,329 genes were differentially expressed (P <
      0.05) for the comparisons of 21-day C vs. 21-day C + 1-day A, 21-day C vs. 21-day
      C + 3-day A, and 21-day C vs. 21-day C + Germ (germination), respectively.
      Functional classifications based on gene set and sub-network enrichment analysis
      were performed to identify pathways and gene sub-networks that underlie
      transcriptome changes in the seeds as they germinate. Sugars, plant hormones,
      photomorphogenesis, and reactive oxygen species were overrepresented at 21-day C
      + 1-day A. At 21-day C + 3-day A, an increase in cellular activities was observed
      as the number of overrepresented pathways greatly increased. Many of the
      metabolic pathways were involved in the biosynthesis of amino acids,
      macromolecules, and energy and carbon skeleton production for subsequent
      germination. The 21-day C + 3-day A and 21-day C + Germ pathways and sub-networks
      were similar and included an overrepresentation of the amino acid biosynthetic
      pathways; however, 21-day C + Germ seeds have an even wider array of cellular
      activities such as translation-related pathways, which are most likely for
      seedling growth. RT-qPCR analysis indicated that the up- and down-regulation of
      HISTONE H3, GASA2, DREBIII-1, CHS, AOS, PIF3, PLD alpha1, and LEA may be
      germination-related since their expression was dramatically changed only in the
      21-day C + Germ seeds. Finally, both short-term alternating temperature and short
      term light exposure up-regulated the expression targets of the central hub HY5 in
      leafy spurge and Arabidopsis, respectively, indicating that a signaling network
      involving HY5 is important for germination.

PMID- 21947438
TI  - Online monitoring of coffee roasting by proton transfer reaction time-of-flight
      mass spectrometry (PTR-ToF-MS): towards a real-time process control for a
      consistent roast profile.
AB  - A real-time automated process control tool for coffee roasting is presented to
      consistently and accurately achieve a targeted roast degree. It is based on the
      online monitoring of volatile organic compounds (VOC) in the off-gas of a drum
      roaster by proton transfer reaction time-of-flight mass spectrometry at a high
      time (1 Hz) and mass resolution (5,500 m/Deltam at full width at half-maximum)
      and high sensitivity (better than parts per billion by volume). Forty-two
      roasting experiments were performed with the drum roaster being operated either
      on a low, medium or high hot-air inlet temperature (= energy input) and the
      coffee (Arabica from Antigua, Guatemala) being roasted to low, medium or dark
      roast degrees. A principal component analysis (PCA) discriminated, for each one
      of the three hot-air inlet temperatures, the roast degree with a resolution of
      better than +/-1 Colorette. The 3D space of the three first principal components
      was defined based on 23 mass spectral profiles of VOCs and their roast degree at
      the end point of roasting. This provided a very detailed picture of the evolution
      of the roasting process and allowed establishment of a predictive model that
      projects the online-monitored VOC profile of the roaster off-gas in real time
      onto the PCA space defined by the calibration process and, ultimately, to control
      the coffee roasting process so as to achieve a target roast degree and a
      consistent roasting.

PMID- 21947439
TI  - MIP sensors--the electrochemical approach.
AB  - This review highlights the importance of coupling molecular imprinting technology
      with methodology based on electrochemical techniques for the development of
      advanced sensing devices. In recent years, growing interest in molecularly
      imprinted polymers (MIPs) in the preparation of recognition elements has led
      researchers to design novel formats for improvement of MIP sensors. Among
      possible approaches proposed in the literature on this topic, we will focus on
      the electrosynthesis of MIPs and on less common hybrid technology (e.g. based on
      electrochemistry and classical MIPs, or nanotechnology). Starting from the early
      work reported in this field, an overview of the most innovative and successful
      examples will be reviewed.

PMID- 21947440
TI  - Partner-assisted emotional disclosure for patients with GI cancer: 8-week follow
      up and processes associated with change.
AB  - PURPOSE: We recently reported that a partner-assisted emotional disclosure
      intervention for gastrointestinal cancer led to improvements in relationship
      quality and intimacy for couples in which the patient initially reported higher
      levels of holding back from discussing cancer-related concerns. The purposes of
      the present study were to examine outcomes at 8-week follow-up and process
      variables that may influence treatment effects. METHODS: One hundred thirty
      couples were randomly assigned to either partner-assisted emotional disclosure or
      an education/support control condition. Participants completed measures of
      relationship quality, intimacy, and psychological distress before randomization,
      post-treatment, and 8 weeks later. Patients in the disclosure intervention
      completed measures of negative affect immediately following each treatment
      session, and their level of expressiveness during the sessions was rated by
      trained observers. Data were analyzed using multilevel modeling. RESULTS: Among
      couples in which the patient initially reported higher levels of holding back,
      the disclosure intervention led to improvements in relationship quality and
      intimacy that were maintained at 8-weeks follow-up. High levels of patient
      expressiveness during the disclosure sessions were associated with improvements
      in relationship quality and intimacy, and high levels of patient negative affect
      immediately following the sessions were associated with reductions in
      psychological distress at the post-test assessment. CONCLUSIONS: For couples in
      which the patient tends to hold back from discussing concerns, partner-assisted
      emotional disclosure is a beneficial intervention leading to improvements in
      relationship functioning that maintain over time. Future research is needed to
      examine methods of enhancing intervention effects, including encouraging patient
      expressiveness and negative affect during the sessions.

PMID- 21947441
TI  - Compliance with fluoride custom trays in irradiated head and neck cancer
      patients.
AB  - PURPOSE: The purpose of this study is to assess compliance with fluoride gel
      custom trays in irradiated head and neck cancer patients. METHODS AND MATERIALS:
      One hundred fifty-five consecutive patients on remission following radiation
      therapy of head and neck cancers were assessed retrospectively for dental care
      practices prior to radiation and prospectively for long-term compliance with
      custom trays from November 2009 to January 2010. A five-item questionnaire was
      filled in by patients in the waiting room, and a 15-item questionnaire by the
      physician in charge during the corresponding follow-up visit. RESULTS: Ten
      percent of patients were edentulous at inclusion. Among dentate patients, 17% had
      total extractions. With a mean follow-up of 24 months, 19% of patients used
      custom trays for over a year. Primary stage, age, and tobacco consumption were
      correlated with compliance with custom trays. More than half of dentate patients
      developed carious lesions, and 8% had stage 1-3 osteoradionecrosis of the whole
      population of edentulous and dentate patients. CONCLUSION: Compliance with custom
      trays was poor in this series. Specific postirradiation dental care follow-up
      visits and education have demonstrated their utility in the era of 2D
      irradiation. We currently advocate an 18-month compliance with custom trays in
      IMRT patients on the basis of the Parsport trial, after which we assess the
      quality of salivary recovery before recommending prolonged use or interruption.
      Data with innovative irradiation techniques are however required.

PMID- 21947442
TI  - Reactive oxygen species and the neuronal fate.
AB  - Aberrant or elevated levels of reactive oxygen species (ROS) can mediate
      deleterious cellular effects, including neuronal toxicity and degeneration
      observed in the etiology of a number of pathological conditions, including
      Alzheimer's and Parkinson's diseases. Nevertheless, ROS can be generated in a
      controlled manner and can regulate redox sensitive transcription factors such as
      NFkappaB, AP-1 and NFAT. Moreover, ROS can modulate the redox state of tyrosine
      phosphorylated proteins, thereby having an impact on many transcriptional
      networks and signaling cascades important for neurogenesis. A large body of
      literature links the controlled generation of ROS at low-to-moderate levels with
      the stimulation of differentiation in certain developmental programs such as
      neurogenesis. In this regard, ROS are involved in governing the acquisition of
      the neural fate-from neural induction to the elaboration of axons. Here, we
      summarize and discuss the growing body of literature that describe a role for ROS
      signaling in neuronal development.

PMID- 21947444
TI  - Structure-based characterization of the binding of peptide to the human
      endophilin-1 Src homology 3 domain using position-dependent noncovalent potential
      analysis.
AB  - Many protein-protein interactions are mediated by a peptide-recognizing domain,
      such as WW, PDZ, or SH3. In the present study, we describe a new method called
      position-dependent noncovalent potential analysis (PDNPA), which can accurately
      characterize the nonbonding profile between the human endophilin-1 Src homology 3
      (hEndo1 SH3) domain and its peptide ligands and quantitatively predict the
      binding affinity of peptide to hEndo1 SH3. In this procedure, structure models of
      diverse peptides in complex with the hEndo1 SH3 domain are constructed by
      molecular dynamics simulation and a virtual mutagenesis protocol. Subsequently,
      three noncovalent interactions associated with each position of the peptide
      ligand in the complexed state are analyzed using empirical potential functions,
      and the resulting potential descriptors are then correlated with the
      experimentally measured affinity on the basis of 1997 hEndo1 SH3-binding peptides
      with known activities, using linear partial least squares regression (PLS) and
      the nonlinear support vector machine (SVM). The results suggest that: (i) the
      electrostatics appears to be more important than steric properties and
      hydrophobicity in the formation of the hEndo1 SH3-peptide complex; (ii) P(-4) of
      the core decapeptide ligand with the sequence pattern P(-6)P(-5)P(-4)P(-3)P(-2)P(
      1)P(0)P(1)P(2)P(3) is the most important position in terms of determining both
      the stability and specificity of the architecture of the complex, and; (iii)
      nonlinear SVM appears to be more effective than linear PLS for accurately
      predicting the binding affinity of a peptide ligand to hEndo1 SH3, whereas PLS
      models are straightforward and easy to interpret as compared to those built by
      SVM.

PMID- 21947443
TI  - The hypothalamus and the neurobiology of drug seeking.
AB  - The hypothalamus is a neural structure critical for expression of motivated
      behaviours that ensure survival of the individual and the species. It is a
      heterogeneous structure, generally recognised to have four distinct regions in
      the rostrocaudal axis (preoptic, supraoptic, tuberal and mammillary). The tuberal
      hypothalamus in particular has been implicated in the neural control of
      appetitive motivation, including feeding and drug seeking. Here we review the
      role of the tuberal hypothalamus in appetitive motivation. First, we review
      evidence that different regions of the hypothalamus exert opposing control over
      feeding. We then review evidence that a similar bi-directional regulation
      characterises hypothalamic contributions to drug seeking and reward seeking.
      Lateral regions of the dorsal tuberal hypothalamus are important for promoting
      reinstatement of drug seeking, whereas medial regions of the dorsal tuberal
      hypothalamus are important for inhibiting this drug seeking after extinction
      training. Finally, we review evidence that these different roles for medial
      versus lateral dorsal tuberal hypothalamus in promoting or preventing
      reinstatement of drug seeking are mediated, at least in part, by different
      populations of hypothalamic neurons as well as the neural circuits in which they
      are located.

PMID- 21947445
TI  - Automatic prediction of flexible regions improves the accuracy of protein-protein
      docking models.
AB  - Computational models of protein-protein docking that incorporate backbone
      flexibility can predict perturbations of the backbone and side chains during
      docking and produce protein interaction models with atomic accuracy. Most
      previous models usually predefine flexible regions by visually comparing the
      bound and unbound structures. In this paper, we propose a general method to
      automatically identify the flexible hinges for domain assembly and the flexible
      loops for loop refinement, in addition to predicting the corresponding movements
      of the identified active residues. We conduct experiments to evaluate performance
      of our approach on two test sets. Comparison of results on test set I between
      algorithms with and without prediction of flexible regions demonstrate the
      superior recovery of energy funnels in many target interactions using the new
      loop refinement model. In addition, our decoys are superior for each target.
      Indeed, the total number of satisfactory models is almost double that of other
      programs. The results on test set II docking tests produced by our domain
      assembly method also show encouraging results. Of the three targets examined, one
      exhibits energy funnel and the best models of the other two targets all meet the
      conditions of acceptable accuracy. Results demonstrate that the automatic
      prediction of flexible backbone regions can greatly improve the performance of
      protein-protein docking models.

PMID- 21947446
TI  - Influence of point defects on the electronic properties of boron nitride
      nanosheets.
AB  - Density functional theory was utilized to study the electronic properties of
      boron nitride (BN) sheets, taking into account the presence of defects. The
      structure considered consisted of a central hexagon surrounded by alternating
      pentagons (three) and heptagons (three). The isocoronene cluster model with an
      armchair edge was used with three different chemical compositions. In the first
      structure, three B-B bonds were formed where one B in the dimer was part of the
      central hexagon. In the second structure, three N-N-N bonds were formed at the
      periphery of the cluster, around the central hexagon. In the third structure,
      three N-N bonds were formed in a similar fashion to the first model. Our results
      indicated that the third structure was the most stable configuration; this
      exhibited planar geometry, semiconductor behavior, and ionic character. To
      explore the effects of doping, we replaced B and N atoms with C atoms,
      considering different atomic positions in the central hexagon. When an N atom was
      replaced with a C atom, the new structure was a semiconductor, but when a B atom
      was replaced with a C atom, the new structure was a semimetal. At the same time,
      the polarity increased, inducing covalent behavior. Replacing two N atoms with
      two C atoms also resulted in a semiconductor, while replacing two B atoms with
      two C atoms yielded a semimetal; in both cases the bonding was covalent. When
      three B (three N) atoms of the central hexagon were replaced with three C atoms,
      the new structure exhibited a transition to a conductor (remained a
      semiconductor) with low polarity. When monovacancies (N) and divacancies (B and
      N) were inserted into the lattice, the system was transformed into a covalent
      semiconductor. Finally, the electrostatic potential surface was calculated in
      order to explore intermolecular properties such as the charge distribution, which
      showed how the reactivity of the boron nitride sheets was affected by doping and
      orbital hybridization.

PMID- 21947448
TI  - Docking, molecular dynamics and quantitative structure-activity relationship
      studies for HEPTs and DABOs as HIV-1 reverse transcriptase inhibitors.
AB  - As a key component in combination therapy for acquired immunodeficiency syndrome
      (AIDS), non-nucleoside reverse transcriptase inhibitors (NNRTIs) have been proven
      to be an essential way in stopping HIV-1 replication. In the present work, in
      silico studies were conducted on a series of 119 NNRTIs, including 1-(2
      hydroxyethoxymethyl)-6-(phenylthio)thymine (HEPT) and
      dihydroalkoxybenzyloxopyrimidine (DABO) derivatives by using the comparative
      molecular field analysis (CoMFA), comparative molecular similarity indices
      analysis (CoMSIA), docking simulations and molecular dynamics (MD). The
      statistical results of the optimal model, the ligand-based CoMSIA one (Q(2) =
      0.48, R(ncv)(2) =0.847, R(pre)(2) = 0.745) validates its satisfactory predictive
      capacity both internally and externally. The contour maps, docking and MD results
      correlate well with each other, drawing conclusions as follows: 1) Compounds with
      bulky substituents in position-6 of ring A, hydrophobic groups around position-
      1, 2, 6 are preferable to the biological activities; 2) Two hydrogen bonds
      between RT inhibitor and the Tyr 318, Lys 101 residues, respectively, and a pi-pi
      bond between the inhibitor and Trp 188 are formed and crucial to the orientation
      of the active conformation of the molecules; 3) The binding pocket is essentially
      hydrophobic, which are determined by residues such as Trp 229, Tyr 318, Val 179,
      Tyr 188 and Val 108, and hydrophobic substituents may bring an improvement to the
      biological activity; 4) DABO and HEPT derivatives have different structures but
      take a similar mechanism to inhibit RT. The potency difference between two
      isomers in HEPTs can be explained by the distinct locations of the 6
      naphthylmethyl substituent and the reasons are explained in details. All these
      results could be employed to alter the structural scaffold in order to develop
      new HIV-1 RT inhibitors that have an improved biological property. To the best of
      our knowledge, this is the first report on 3D-QSAR modeling of this series of
      HEPT and DABO NNRTs. The QSAR model and the information derived, we hope, will be
      of great help in presenting clear guidelines and accurate activity predictions
      for newly designed HIV-1 reverse transcriptase (RT) inhibitor.

PMID- 21947447
TI  - Putative binding modes of Ku70-SAP domain with double strand DNA: a molecular
      modeling study.
AB  - The channel structure of the Ku protein elegantly reveals the mechanistic basis
      of sequence-independent DNA-end binding, which is essential to genome integrity
      after exposure to ionizing radiation or in V(D)J recombination. However,
      contradicting evidence indicates that this protein is also involved in the
      regulation of gene expression and in other regulatory processes with intact
      chromosomes. This computational study predicts that a putative DNA binding domain
      of this protein, the SAP domain, can form DNA-bound complexes with relatively
      high affinities (DeltaG ~ -20 kcal mol(-1)). The binding modes are searched by
      low frequency vibration modes driven by the fully flexible docking method while
      binding affinities are calculated by the molecular mechanics Poisson-Boltzmann
      surface area (MM-PBSA) method. We find this well defined 5 kDa domain with a
      helix-extended loop-helix structure is suitable to form favorable electrostatic
      and hydrophobic interactions with either the major groove or the minor groove of
      DNA. The calculation also reveals the sequence specified binding preference which
      may relate to the observed pause sites when Ku translocates along DNA and the
      perplex binding of Ku with circular DNA.

PMID- 21947449
TI  - Molecular dynamics modeling of the sub-THz vibrational absorption of thioredoxin
      from E. coli.
AB  - Sub-terahertz (THz) vibrational modes of the protein thioredoxin in a water
      environment were simulated using molecular dynamics (MD) in order to find the
      conditions needed for simulation convergence, improve the correlation between
      experimental and simulated absorption frequencies, and ultimately enhance the
      predictive capabilities of computational modeling. Thioredoxin from E. coli was
      used as a model molecule for protocol development and to optimize the simulation
      parameters. The empirically parameterized software packages Amber 8 and 10 were
      used in this work. Using atomic trajectories from the constant energy and volume
      MD simulations, thioredoxin's sub-THz vibrational spectra and absorption
      coefficients were calculated in a quasi-harmonic approximation. An optimal
      production run length ~100 ps was found, in agreement with experimental data on
      thioredoxin relaxation dynamics. At the same time, a new procedure was developed
      for averaging correlation matrices of atomic coordinates in MD simulations. In
      particular, the open source package ptraj was edited to improve a matrix
      analyzing function. Averaging only six matrices gave much more consistent
      results, with absorption peak intensities exceeding those from the individual
      spectra and a rather good correlation between simulated vibrational frequencies
      and experimental data.

PMID- 21947450
TI  - A theoretical study on the reaction mechanism of O2 with C4H9* radical.
AB  - Ab initio calculations have been performed using the complete basis set model
      (CBS-QB3) to study the reaction mechanism of butane radical (C(4)H(9)*) with
      oxygen (O(2)). On the calculated potential energy surface, the addition of O(2)
      to C(4)H(9)* forms three intermediates barrierlessly, which can undergo
      subsequent isomerization or decomposition reaction leading to various products:
      HOO* + C(4)H(8), C(2)H(5)* + CH(2)CHOOH, OH* + C(3)H(7)CHO, OH* + cycle
      C(4)H(8)O, CH(3)* + CH(3)CHCHOOH, CH(2)OOH* + C(3)H(6). Five pathways are
      supposed in this study. After taking into account the reaction barrier and
      enthalpy, the most possible reaction pathway is C(4)H(9)* + O(2) -> IM1 -> TS5 ->
      IM3 -> TS6 -> IM4 -> TS7 -> OH* + cycle-C(4)H(8)O.

PMID- 21947451
TI  - An evaluation of prior influence on the predictive ability of Bayesian model
      averaging.
AB  - Model averaging is gaining popularity among ecologists for making inference and
      predictions. Methods for combining models include Bayesian model averaging (BMA)
      and Akaike's Information Criterion (AIC) model averaging. BMA can be implemented
      with different prior model weights, including the Kullback-Leibler prior
      associated with AIC model averaging, but it is unclear how the prior model weight
      affects model results in a predictive context. Here, we implemented BMA using the
      Bayesian Information Criterion (BIC) approximation to Bayes factors for building
      predictive models of bird abundance and occurrence in the Chihuahuan Desert of
      New Mexico. We examined how model predictive ability differed across four prior
      model weights, and how averaged coefficient estimates, standard errors and
      coefficients' posterior probabilities varied for 16 bird species. We also
      compared the predictive ability of BMA models to a best single-model approach.
      Overall, Occam's prior of parsimony provided the best predictive models. In
      general, the Kullback-Leibler prior, however, favored complex models of lower
      predictive ability. BMA performed better than a best single-model approach
      independently of the prior model weight for 6 out of 16 species. For 6 other
      species, the choice of the prior model weight affected whether BMA was better
      than the best single-model approach. Our results demonstrate that parsimonious
      priors may be favorable over priors that favor complexity for making predictions.
      The approach we present has direct applications in ecology for better predicting
      patterns of species' abundance and occurrence.

PMID- 21947452
TI  - Ischemic exercise hyperemia in the human forearm: reproducibility and roles of
      adenosine and nitric oxide.
AB  - The roles of local metabolites in reactive and exercise hyperemia remain
      incompletely understood. A maximum metabolic stimulus caused by ischemic exercise
      (IE) could potentially fully activate all vasodilator pathways and limit
      potential redundancy amongst vasoactive substances. We tested the hypotheses that
      IE elicits a reproducible hyperemic response in the forearm and that adenosine
      (ADO) and nitric oxide (NO) contribute to this response. In separate protocols,
      forearm blood flow (FBF) was measured with venous occlusion plethysmography
      following IE trials consisting of 5 min of ischemia and rhythmic forearm handgrip
      exercise (performed during last 2 min of ischemia). In protocol 1 (n = 8), FBF
      was measured after three trials of IE. In protocol 2 (n = 9), subjects performed
      IE during control (saline), aminophylline (APH; adenosine receptor antagonist),
      and combined APH/N (G)-monomethyl-L-arginine (L-NMMA; NOS inhibition) infusions.
      In protocol 1, coefficients of variation for total (area under the curve)
      DeltaFBF and DeltaFVC (forearm vascular conductance) following IE were 10.4 +/-
      1.0% and 14.9 +/- 1.0%, respectively. In protocol 2, peak DeltaFBF was similar
      for saline and APH trials. Peak DeltaFBF for the APH+L: -NMMA trial was greater
      than that of the APH trial (P = 0.03), and peak DeltaFVC was marginally non
      significant (P = 0.053). Total DeltaFBF (54.8 +/- 3.9, 55.2 +/- 5.4, and 60.4 +/-
      4.8 ml 100 ml(-1); P = 0.43) and DeltaFVC (51.4 +/- 3.5, 52.1 +/- 5.5, and 56.5
      +/- 5.0 ml 100 ml(-1) 100 mmHg(-1); P = 0.52) were similar for saline, APH, and
      APH+L: -NMMA, respectively. Our data suggest that (1) the hyperemic response to
      IE is reproducible and (2) inhibition of ADO alone or combined ADO and NO does
      not blunt the hyperemic response following IE.

PMID- 21947453
TI  - Contractile function and sarcolemmal permeability after acute low-load resistance
      exercise with blood flow restriction.
AB  - Conflicting findings have been reported regarding muscle damage with low
      intensity resistance exercise with blood flow restriction (BFR) by pressure
      cuffs. This study investigated muscle function and muscle fibre morphology after
      a single bout of low-intensity resistance exercise with and without BFR. Twelve
      physically active subjects performed unilateral knee extensions at 30% of their
      one repetition maximum (1RM), with partial BFR on one leg and the other leg
      without occlusion. With the BFR leg, five sets were performed to concentric
      torque failure, and the free-flow leg repeated the exact same number of
      repetitions and sets. Biopsies were obtained from vastus lateralis before and 1,
      24 and 48 h after exercise. Maximum isometric torque (MVC) and resting tension
      were measured before and after exercise and at 4, 24, 48, 72, 96 and 168 h post
      exercise. The results demonstrated significant decrements in MVC (lasting >=48 h)
      and delayed onset muscle soreness in both legs, and increased resting tension for
      the occluded leg both acutely and at 24 h post-exercise. The percentage of muscle
      fibres showing elevated intracellular staining of the plasma protein tetranectin,
      a marker for sarcolemmal permeability, was significantly increased from 9% before
      exercise to 27-38% at 1, 24 and 48 h post-exercise for the BFR leg. The changes
      in the free-flow leg were significant only at 24 h (19%). We conclude that an
      acute bout of low-load resistance exercise with BFR resulted in changes
      suggesting muscle damage, which may have implications both for safety aspects and
      for the training stimulus with BFR exercise.

PMID- 21947454
TI  - The effect of exercise-induced hypoxemia on blood redox status in well-trained
      rowers.
AB  - Exercise-induced arterial hypoxemia (EIAH), characterized by decline in arterial
      oxyhemoglobin saturation (SaO(2)), is a common phenomenon in endurance athletes.
      Acute intensive exercise is associated with the generation of reactive species
      that may result in redox status disturbances and oxidation of cell
      macromolecules. The purpose of the present study was to investigate whether EIAH
      augments oxidative stress as determined in blood plasma and erythrocytes in well
      trained male rowers after a 2,000-m rowing ergometer race. Initially, athletes
      were assigned into either the normoxemic (n = 9, SaO(2) >92%, [Formula: see
      text]: 62.0 +/- 1.9 ml kg(-1) min(-1)) or hypoxemic (n = 12, SaO(2) <92%,
      [Formula: see text]: 60.5 +/- 2.2 ml kg(-1 )min(-1), mean +/- SEM) group,
      following an incremental [Formula: see text] test on a wind resistance braked
      rowing ergometer. On a separate day the rowers performed a 2,000-m all-out effort
      on the same rowing ergometer. Following an overnight fast, blood samples were
      drawn from an antecubital vein before and immediately after the termination of
      the 2,000-m all-out effort and analyzed for selective oxidative stress markers.
      In both the normoxemic (SaO(2): 94.1 +/- 0.9%) and hypoxemic (SaO(2): 88.6 +/-
      2.4%) rowers similar and significant exercise increase in serum thiobarbituric
      acid-reactive substances, protein carbonyls, catalase and total antioxidant
      capacity concentration were observed post-2,000 m all-out effort. Exercise
      significantly increased the oxidized glutathione concentration and decreased the
      ratio of reduced (GSH)-to-oxidized (GSSG) glutathione in the normoxemic group
      only, whereas the reduced form of glutathione remained unaffected in either
      groups. The increased oxidation of GSH to GSSG in erythrocytes of normoxemic
      individuals suggest that erythrocyte redox status may be affected by the oxygen
      saturation degree of hemoglobin. Our findings indicate that exercise-induced
      hypoxemia did not further affect the increased blood oxidative damage of lipids
      and proteins observed after a 2,000-m rowing ergometer race in highly-trained
      male rowers. The present data do not support any potential link between exercise
      induced hypoxemia, oxidative stress increase and exercise performance.

PMID- 21947455
TI  - Body metabolic rate and electromyographic activities of antigravitational muscles
      in supine and standing postures.
AB  - We measured metabolic (oxygen uptake, carbon dioxide production, respiratory
      ratio), cardio-circulatory (heart rate, systolic and diastolic arterial blood
      pressure, rate-pressure product, an index of myocardial oxygen consumption
      calculated by multiplying heart rate by systolic pressure) and electromyographic
      (integrated electromyographic activities of two antigravitational muscles of the
      lower limb, soleus and gastrocnemius) variables on 12 young healthy subjects in
      supine and standing positions at rest. We found statistically significant
      increments of oxygen uptake, carbon dioxide production, heart rate and integrated
      electromyographic activities in standing versus supine position. Rate-pressure
      product increased but not significantly, and no other significant changes were
      detected. We conclude that postural changes influence metabolic rate,
      antigravitational muscle reflex activities, and heart rate. A significant
      positive correlation was found between oxygen uptake and carbon dioxide
      production and integrated electromyographic activities of antigravitational
      muscles, while the same was not found for cardio-circulatory variables. These
      results suggest that the increased metabolic rate in standing position is, at
      least in part, due to antigravitational muscle tone.

PMID- 21947456
TI  - Effects of 12-week Tai Chi training on soleus H-reflex and muscle strength in
      older adults: a pilot study.
AB  - The purpose of this study was to determine the effects of 12-week Tai Chi (TC)
      training on the soleus (SOL) H-reflex modulation and plantarflexion muscle
      strength in older adults. Twenty volunteers were assigned into training (N = 14;
      72.2 +/- 3.7 years of age) and control (N = 6; 74.2 +/- 6.1 years of age) groups.
      The participants in the TC group practiced Yang style TC 1 h per session, 3
      sessions per week, for 12 weeks, guided by a qualified TC instructor. The ratio
      of the maximal peak-to-peak amplitude of SOL H-reflex (H (max)) to M-wave (M
      (max)) was determined during bipedal standing under four sensory conditions:
      stable surface and eyes open (SO), stable surface and eyes closed (SC), unstable
      surface and eyes open (UO), and unstable surface and eyes closed (UC). The
      maximal isometric plantarflexion muscle strength was also assessed by using a
      dynamometer. The results showed that the SOL H (max)/M (max) ratio increased
      significantly after the 12 weeks of TC training under the SC (37.0%), UO (33.3%)
      and UC (36.0%) conditions (P < 0.05). The maximal plantarflexion strength also
      improved significantly after training (19.8%; P < 0.05). In contrast, the control
      group showed no significant changes in all measurements after the 12 weeks.

PMID- 21947457
TI  - Cranial nerve vascular compression syndromes of the trigeminal, facial and vago
      glossopharyngeal nerves: comparative anatomical study of the central myelin
      portion and transitional zone; correlations with incidences of corresponding
      hyperactive dysfunctional syndromes.
AB  - OBJECTIVE: The aim of this study was to evaluate the anatomy of the central
      myelin portion and the central myelin-peripheral myelin transitional zone of the
      trigeminal, facial, glossopharyngeal and vagus nerves from fresh cadavers. The
      aim was also to investigate the relationship between the length and volume of the
      central myelin portion of these nerves with the incidences of the corresponding
      cranial dysfunctional syndromes caused by their compression to provide some more
      insights for a better understanding of mechanisms. METHODS: The trigeminal,
      facial, glossopharyngeal and vagus nerves from six fresh cadavers were examined.
      The length of these nerves from the brainstem to the foramen that they exit were
      measured. Longitudinal sections were stained and photographed to make
      measurements. The diameters of the nerves where they exit/enter from/to
      brainstem, the diameters where the transitional zone begins, the distances to the
      most distal part of transitional zone from brainstem and depths of the
      transitional zones were measured. Most importantly, the volume of the central
      myelin portion of the nerves was calculated. Correlation between length and
      volume of the central myelin portion of these nerves and the incidences of the
      corresponding hyperactive dysfunctional syndromes as reported in the literature
      were studied. RESULTS: The distance of the most distal part of the transitional
      zone from the brainstem was 4.19  +/-  0.81 mm for the trigeminal nerve, 2.86  +/
      1.19 mm for the facial nerve, 1.51  +/-  0.39 mm for the glossopharyngeal
      nerve, and 1.63  +/-  1.15 mm for the vagus nerve. The volume of central myelin
      portion was 24.54  +/-  9.82 mm(3) in trigeminal nerve; 4.43  +/-  2.55 mm(3) in
      facial nerve; 1.55  +/-  1.08 mm(3) in glossopharyngeal nerve; 2.56  +/-  1.32
      mm(3) in vagus nerve. Correlations (p  < 0.001) have been found between the
      length or volume of central myelin portions of the trigeminal, facial,
      glossopharyngeal and vagus nerves and incidences of the corresponding diseases.
      CONCLUSION: At present it is rather well-established that primary trigeminal
      neuralgia, hemifacial spasm and vago-glossopharyngeal neuralgia have as one of
      the main causes a vascular compression. The strong correlations found between the
      lengths and volumes of the central myelin portions of the nerves and the
      incidences of the corresponding diseases is a plea for the role played by this
      anatomical region in the mechanism of these diseases.

PMID- 21947458
TI  - Arteriovenous malformation of the pineal gland.

PMID- 21947459
TI  - Re: Male gender is a risk factor for recurrent appendicitis following
      nonoperative treatment.

PMID- 21947460
TI  - Re: The necessity and reliability of intraoperative parathyroid hormone (PTH)
      testing in patients with mild hyperparathyroidism and PTH levels in the normal
      range.

PMID- 21947462
TI  - Isolation and partial characterization of a virulent bacteriophage IHQ1 specific
      for Aeromonas punctata from stream water.
AB  - Aeromonas punctata is the causative agent of septicemia, diarrhea, wound
      infections, meningitis, peritonitis, and infections of the joints, bones and
      eyes. Bacteriophages are often considered alternative agents for controlling
      bacterial infection and contamination. In this study, we described the isolation
      and preliminary characterization of bacteriophage IHQ1 (family Myoviridae) active
      against the Gram-negative bacterial strain A. punctata. This virulent
      bacteriophage was isolated from stream water sample. Genome analysis indicated
      that phage IHQ1 was a double-stranded DNA virus with an approximate genome size
      of 25-28 kb. The initial characterization of this newly isolated phage showed
      that it has a narrow host range and infects only A. punctata as it failed to
      infect seven other clinically isolated pathogenic strains, i.e., methicillin
      resistant Staphylococcus aureus 6403, MRSA 17644, Acinetobacter 33408,
      Acinetobacter 1172, Pseudomonas aeruginosa 22250, P. aeruginosa 11219, and
      Escherichia coli. Proteomic pattern of phage IHQ1, generated by SDS-PAGE using
      purified phage particles, showed three major and three minor protein bands with
      molecular weights ranging from 25 to 70 kDa. The adsorption rate of phage IHQ1 to
      the host bacterium was also determined, which was significantly enhanced by the
      addition of 10 mM CaCl(2). From the single-step growth experiment, it was
      inferred that the latent time period of phage IHQ1 was 24 min and a burst size of
      626 phages per cell. Moreover, the pH and thermal stability of phage IHQ1 were
      also investigated. The maximum stability of the phage was observed at optimal pH
      7.0, and it was totally unstable at extreme acidic pH 3; however, it was
      comparatively stable at alkaline pH 11.0. At 37 degrees C the phage showed
      maximum number of plaques, and the viability was almost 100%. The existence of
      Aeromonas bacteriophage is very promising for the eradication of this
      opportunistic pathogen and also for future applications such as the design of new
      detection and phage typing (diagnosis) methods. The specificity of the
      bacteriophage for A. punctata makes it an attractive candidate for phage therapy
      of A. punctata infections.

PMID- 21947463
TI  - A possible mechanism of isolated oculomotor nerve palsy by apoplexy of pituitary
      adenoma without cavernous sinus invasion: a report of two cases.
AB  - Isolated oculomotor nerve palsy occasionally occurs in patients with cavernous
      sinus invasion with or without pituitary apoplexy. We describe two cases of
      pituitary apoplexy without cavernous sinus invasion presenting with isolated
      oculomotor palsy. In both cases, computed tomography (CT) showed erosion of the
      right posterior clinoid process. Magnetic resonance imaging (MRI) depicted
      pituitary adenoma with apoplexy protruding latero-posteriorly to the right
      cavernous sinus. The medio-posterior wall of the cavernous sinus was markedly
      displaced latero-posteriorly by the tumor, and there was no evidence of cavernous
      sinus invasion. Oculomotor palsy may be caused first by unilateral erosion of the
      posterior clinoid process, resulting in latero-posterior protrusion of the
      adenoma. Hemorrhage may result in sudden kinking of the oculomotor nerve at the
      entrance of the oculomotor trigone.

PMID- 21947464
TI  - Thrombospondin 1: a protective "matri-cellular" signal in the stressed heart.

PMID- 21947461
TI  - In-depth characterization via complementing culture-independent approaches of the
      microbial community in an acidic hot spring of the Colombian Andes.
AB  - The microbial community of a Colombian high mountain hot spring, El Coquito, was
      analyzed using three different culture-independent assessments of 16S ribosomal
      RNA genes: clone libraries, pyrosequencing of the V5-V6 hypervariable region, and
      microarray. This acidic spring had a diverse community composed mainly of
      Bacteria that shared characteristics with those from other hot springs and
      extreme acidic environments. The microbial community was dominated by
      Proteobacteria, Firmicutes, and Planctomycetes and contained chemotrophic
      bacteria potentially involved in cycling of ferrous and sulfur-containing
      minerals and phototrophic organisms, most of which were eukaryotic micro-algae.
      Despite the presence of a large proportion of novel, unclassified sequences, the
      taxonomic profiles obtained with each strategy showed similarities at higher
      taxonomic levels. However, some groups, such as Spirochaetes and Aquificae, were
      identified using only one methodology, and more taxa were detected with the gene
      array, which also shared more groups with the pyrosequencing data. Overall, the
      combined use of different approaches provided a broader view of the microbial
      community in this acidic hot spring.

PMID- 21947465
TI  - Approaching the threshold for predicting preeclampsia: monitoring angiogenic
      balance during pregnancy.

PMID- 21947466
TI  - Isolated diastolic hypotension and incident heart failure in older adults.
AB  - Aging is often associated with increased systolic blood pressure and decreased
      diastolic blood pressure. Isolated systolic hypertension or an elevated systolic
      blood pressure without an elevated diastolic blood pressure is a known risk
      factor for incident heart failure in older adults. In the current study, we
      examined whether isolated diastolic hypotension, defined as a diastolic blood
      pressure <60 mm Hg and a systolic blood pressure >=100 mm Hg, is associated with
      incident heart failure. Of the 5795 Medicare-eligible community-dwelling adults
      age >=65 years in the Cardiovascular Health Study, 5521 were free of prevalent
      heart failure at baseline. After excluding 145 individuals with baseline systolic
      blood pressure <100 mm Hg, the final sample included 5376 participants, of whom
      751 (14%) had isolated diastolic hypotension. Propensity scores for isolated
      diastolic hypotension were calculated for each of the 5376 participants and used
      to match 545 and 2348 participants with and without isolated diastolic
      hypotension, respectively, who were balanced on 58 baseline characteristics.
      During >12 years of median follow-up, centrally adjudicated incident heart
      failure developed in 25% and 20% of matched participants with and without
      isolated diastolic hypotension, respectively (hazard ratio associated with
      isolated diastolic hypotension: 1.33 [95% CI: 1.10-1.61]; P=0.004). Among the
      5376 prematch individuals, multivariable-adjusted hazard ratio for incident heart
      failure associated with isolated diastolic hypotension was 1.29 (95% CI: 1.09
      1.53; P=0.003). As in isolated systolic hypertension, among community-dwelling
      older adults without prevalent heart failure, isolated diastolic hypotension is
      also a significant independent risk factor for incident heart failure.

PMID- 21947467
TI  - A novel role for an endothelial adrenergic receptor system in mediating
      catecholestradiol-induced proliferation of uterine artery endothelial cells.
AB  - Sequential conversion of estradiol-17beta to its biologically active
      catecholestradiols, 2-hydroxyestradiol (OHE(2)) and 4-OHE(2), contributes
      importantly to its angiogenic effects on uterine artery endothelial cells (UAECs)
      derived from pregnant, but not nonpregnant ewes via an estrogen receptor
      independent mechanism. Because catecholestradiols and catecholamines exhibit
      structural similarities and have high affinity for alpha- and beta-adrenergic
      receptors (ARs), we investigated whether the endothelial alpha- or beta-ARs
      mediate catecholestradiol-induced proliferation of P-UAECs and whether
      catecholamines alter these responses. Western analyses revealed expression of
      specific AR subtypes in nonpregnant UAECs and P-UAECs, including alpha(2)-,
      beta(2)-, and beta(3)-ARs but not alpha(1)- and beta(1)-ARs. Levels of beta(2)
      ARs and beta(3)-ARs were unaltered by pregnancy, whereas alpha(2)-ARs were
      decreased. Norepinephrine and epinephrine increased P-UAEC, but not nonpregnant
      UAEC proliferation, and these effects were suppressed by propranolol (beta-AR
      blocker) but not phentolamine (alpha-AR blocker). Catecholamines combinations
      with 2-OHE(2) or 4-OHE(2) enhanced P-UAEC mitogenesis. Catecholestradiol-induced
      P-UAEC proliferation was also inhibited by propranolol but not phentolamine.
      beta(2)-AR and beta(3)-AR antagonists (ICI 118 551and SR 59230A, respectively)
      abrogated the mitogenic effects of both 2-OHE(2) and 4-OHE(2). Stimulation of
      beta(2)-ARs and beta(3)-ARs using formoterol and BRL 37344 dose-dependently
      stimulated P-UAEC proliferation, which was abrogated by ICI 118 551 and SR
      59230A, respectively. Proliferation effects of both catecholamines and
      catecholestradiols were only observed in P-UAECs (not nonpregnant UAECs) and were
      mediated via beta(2)-ARs and beta(3)-ARs. We demonstrate for the first time
      convergence of the endothelial AR and estrogenic systems in regulating
      endothelial proliferation, thus providing a distinct evolutionary advantage for
      modulating uterine perfusion during stressful pregnancies.

PMID- 21947468
TI  - Threshold of soluble fms-like tyrosine kinase 1/placental growth factor ratio for
      the imminent onset of preeclampsia.
AB  - It has not been clarified whether thresholds of soluble fms-like tyrosine kinase
      1 (sFlt-1), placental growth factor (PlGF), soluble endoglin, and the sFlt-1/PlGF
      ratio for the imminent onset of preeclampsia (PE) exist. We hypothesized that
      onset thresholds for the imminent onset of PE could be determined by the
      distributions of these 4 markers just after the onset of PE. Study subjects were
      51 PE after the onset of PE; 36 of PE, 20 of gestational hypertension, 142 of a
      small-for-gestational-age infant, and 400 of normal pregnant controls at 19 to 25
      and 27 to 31 weeks of gestation in a prospective cohort study. The current data
      supported our hypothesis that onset thresholds of sFlt-1 and the sFlt-1/PlGF
      ratio exist. The onset thresholds of the sFlt-1/PlGF at 26 to 31 weeks of
      gestation were useful for detecting imminent PE with the onset at <36 weeks of
      gestation, showing sensitivity of 0.36 and a positive likelihood ratio and 95th
      percent CIs of 38 (11-132); when positive, PE occurred at 2.2+/-0.6 weeks (range:
      1.4-3.0 weeks) after the measurement of the sFlt-1/PlGF ratio. The combination of
      sFlt-1 at 26 to 31 weeks of gestation, past history of gestational hypertension
      or PE, prepregnancy body mass index, and mean blood pressure at 16 to 23 weeks of
      gestation was useful for detecting PE with onset of <36 weeks of gestation,
      showing sensitivity of 0.82, and a positive likelihood ratio (95% CI) of 42 (20
      88). In conclusion, the onset threshold of sFlt-1/PlGF existed and might be
      useful for detecting the imminent onset of PE.

PMID- 21947469
TI  - Mechanism of heme-heme oxygenase system impairment of endothelium contraction in
      the spontaneously hypertensive rat.

PMID- 21947471
TI  - Endogenous thrombospondin 1 protects the pressure-overloaded myocardium by
      modulating fibroblast phenotype and matrix metabolism.
AB  - The matricellular protein thrombospondin (TSP) 1 is induced after tissue injury
      and may regulate reparative responses by activating transforming growth factor
      beta, by suppressing angiogenesis and by modulating inflammation and matrix
      metabolism. We hypothesized that endogenous TSP-1 may be involved in the
      pathogenesis of cardiac remodeling in the pressure-overloaded heart. Myocardial
      TSP-1 expression was increased in a mouse model of pressure overload because of
      transverse aortic constriction. TSP-1(-/-) mice exhibited increased early
      hypertrophy and enhanced late dilation in response to pressure overload. Pressure
      overloaded TSP-1 null mice had intense degenerative cardiomyocyte changes,
      exhibiting more extensive sarcomeric loss and sarcolemmal disruption when
      compared with wild-type hearts. Accentuated hypertrophy and cardiomyocyte injury
      in TSP-1(-/-) hearts was accompanied by increased myofibroblast density. However,
      despite a 2-fold higher infiltration of the cardiac interstitium with
      myofibroblasts, pressure-overloaded TSP-1 null hearts did not exhibit
      significantly increased collagen content when compared with wild-type hearts. The
      disproportionately low collagen content in TSP-1 null hearts was attributed to
      infiltration with abundant, but functionally defective, fibroblasts that
      exhibited impaired myofibroblast differentiation and reduced collagen expression
      in comparison with wild-type fibroblasts. Impaired myofibroblast activation in
      TSP-1 null hearts was associated with reduced Smad2 phosphorylation reflecting
      defective transforming growth factor-beta signaling. Moreover, TSP-1 null hearts
      had increased myocardial matrix metalloproteinase 3 expression and enhanced
      matrix metalloproteinase 9 activation after pressure overload. TSP-1 upregulation
      in the pressure-overloaded heart critically regulates fibroblast phenotype and
      matrix remodeling by activating transforming growth factor-beta signaling and by
      promoting matrix preservation, thus preventing chamber dilation.

PMID- 21947470
TI  - Mechanisms of enhanced vascular reactivity in preeclampsia.
AB  - Preeclamptic women have enhanced blood pressure response to angiotensin II and
      extensive systemic vascular infiltration of neutrophils. Neutrophils release
      reactive oxygen species that might activate the RhoA kinase pathway to enhance
      vascular reactivity. We hypothesized that enhanced vascular reactivity in
      preeclampsia is attributed to neutrophil-mediated reactive oxygen species
      activation of the RhoA kinase pathway. Omental arteries were obtained at cesarean
      section and studied using a myograph system. We found that arteries of
      preeclamptic women had extensive infiltration of neutrophils and enhanced
      reactivity to angiotensin II. Treatment of arteries of normal pregnant women with
      reactive oxygen species or activated neutrophils enhanced vessel reactivity to
      angiotensin II mimicking preeclamptic vessels. Pretreatment with superoxide
      dismutase/catalase to quench reactive oxygen species or RhoA kinase inhibitor
      blocked enhanced responses in preeclamptic and normal vessels. Reactive oxygen
      species also enhanced vessel reactivity to norepinephrine, which was blocked by
      RhoA kinase inhibition. Treatment of arteries with reactive oxygen species
      increased RhoA kinase activity 3-fold, whereas culture of human vascular smooth
      muscle cells with angiotensin II and activated neutrophils or reactive oxygen
      species resulted in phosphorylation of key proteins in the RhoA kinase pathway.
      We conclude that enhanced vascular reactivity of omental arteries in preeclampsia
      is attributed to reactive oxygen species activation of the RhoA kinase pathway
      and that enhanced vascular reactivity is likely attributed to the infiltration of
      neutrophils. We speculate that neutrophil infiltration into systemic vasculature
      of preeclamptic women is an important mechanism for hypertension.

PMID- 21947472
TI  - Aging, blood pressure, and heart failure: what are the connections?

PMID- 21947473
TI  - Upregulation of heme oxygenase 1 by hemin impairs endothelium-dependent
      contractions in the aorta of the spontaneously hypertensive rat.
AB  - Heme oxygenase converts heme to carbon monoxide, biliverdin (subsequently
      converted to bilirubin), and free iron. Pharmacological induction of heme
      oxygenase 1 has an antihypertensive effect in the spontaneously hypertensive rat.
      The present study investigated whether upregulation of heme oxygenase 1 by hemin
      reduces endothelial dysfunction in this animal. Thirty-six-week-old rats were
      divided into a hemin treatment (50 mg/kg, IP injection, once) and a control
      group. Aortas were isolated for the measurement of isometric tension, production
      of reactive oxygen species, and heme oxygenase activity, as well as gene and
      protein expressions. Hemin treatment augmented the expression and activity of
      heme oxygenase 1. This in vivo induction of heme oxygenase 1, but not in vitro
      incubation with the heme oxygenase products carbon monoxide or bilirubin, led to
      an improvement of endothelial function in that acetylcholine-induced relaxations
      were potentiated and acetylcholine- and calcium ionophore-induced contractions
      were attenuated. Free radical production was suppressed by hemin treatment,
      judging from the results of 2',7'-dichlorodihydrofluoresein diacetate staining,
      dihydroethidium staining, and lucigenin chemiluminescence, which was explained by
      the decreased expressions of NADPH oxidase 2 and cyclooxygenase 1. The production
      of prostacyclin was decreased by heme oxygenase 1 induction, which was explained
      by a lower expression of cyclooxygenase 1. Contractions to vasoconstrictor
      concentrations of prostacyclin and its mimetic iloprost were attenuated,
      suggesting that the responsiveness of thromboxane-prostanoid receptors to
      prostacyclin was decreased in hemin-treated rats. The suppressed production of
      free radicals and prostacyclin and the decrease of thromboxane-prostanoid
      receptors sensitivity concur to explain the impairment of endothelium-dependent
      contractions caused by heme oxygenase 1 induction by hemin.

PMID- 21947474
TI  - Siderophore-mediated iron uptake in two clades of Marinobacter spp. associated
      with phytoplankton: the role of light.
AB  - Iron is an essential element for oceanic microbial life but its low
      bioavailability limits microorganisms in large areas of the oceans. To acquire
      this metal many marine bacteria produce organic chelates that bind and transport
      iron (siderophores). We have previously shown that algal-associated heterotrophic
      bacteria belonging to the gamma-proteobacterial Marinobacter genus release the
      siderophore vibrioferrin (VF). The iron-VF complex was shown to be both far more
      photolabile than all previously examined photolabile siderophores and to generate
      a photoproduct incapable of re-chelating the released iron. Thus, the photo
      generated iron was shown to be highly bioavailable both to the producing
      bacterium and its algal partner. In exchange, we proposed that algal cells
      produced dissolved organic matter that helped support bacterial growth and
      ultimately fueled the biosynthesis of VF through a light-dependent "carbon for
      iron mutualism". While our knowledge of the importance of light to phototrophs is
      vast, there are almost no studies that examine the effects of light on microbial
      heterotrophs. Here, we characterize iron uptake mechanisms in "algal-associated"
      VF-producers. Fe uptake by a VF knock-out mutant mimics the wild-type strain and
      demonstrates the versatility of iron uptake mechanisms in Marinobacter VF
      producers. We also show that VF-producers selectively regulate a subset of their
      siderophore-dependent iron uptake genes in response to light exposure. The
      regulation of iron uptake and transport genes by light is consistent with the
      light driven algal-bacterial "carbon for iron mutualism" hypothesis in the marine
      environment.

PMID- 21947475
TI  - Composition and functional role of the mucus layers in the intestine.
AB  - In discussions on intestinal protection, the protective capacity of mucus has not
      been very much considered. The progress in the last years in understanding the
      molecular nature of mucins, the main building blocks of mucus, has, however,
      changed this. The intestinal enterocytes have their apical surfaces covered by
      transmembrane mucins and the whole intestinal surface is further covered by
      mucus, built around the gel-forming mucin MUC2. The mucus of the small intestine
      has only one layer, whereas the large intestine has a two-layered mucus where the
      inner, attached layer has a protective function for the intestine, as it is
      impermeable to the luminal bacteria.

PMID- 21947476
TI  - The new asylums in the community: severely ill psychiatric patients living in
      psychiatric supported housing facilities. A Danish register-based study of
      prognostic factors, use of psychiatric services, and mortality.
AB  - INTRODUCTION: Reorganization of psychiatric treatment in Denmark involved a
      declining number of psychiatric long-stay beds and an increasing number of
      psychiatric supported housing facilities in the community. Very few studies have
      focused on the population in such facilities. METHODS: Information was generated
      combining addresses of supported psychiatric housing facilities with information
      from the Danish Civil Registration System to create a case register of persons
      living in supported psychiatric housing facilities. Through linkage with the
      Danish Psychiatric Central Register, we examined predictors of becoming a
      resident in a psychiatric housing facility, use of psychiatric services around
      the time of entrance to a supported psychiatric housing facility, and mortality
      rates for residents in a psychiatric housing facility compared to non-residents
      and to persons in the general population who never experienced a psychiatric
      admission. RESULTS: We identified schizophrenia as the strongest diagnostic
      predictor of becoming a resident in a supported psychiatric housing facility,
      followed by organic mental disorders, substance abuse, and affective disorder. In
      addition, the higher the number of psychiatric bed days, the higher the risk.
      Compared to the years before the first entrance to a supported psychiatric
      housing facility, the number of bed days in the year following the first entrance
      dropped more among residents than among comparable psychiatric patients.
      Mortality rates were slightly higher among residents in a supported psychiatric
      housing facility than among comparable psychiatric patients, but more than
      tenfold higher when compared to the general population of Danes. CONCLUSION: The
      vast majority of persons who became residents in supported psychiatric housing
      facilities had previously been diagnosed with schizophrenia, schizophrenia-like
      disorders, and organic mental disorders, and a large proportion had substance
      abuse and a high use of bed days. Moving into such a facility reduced the number
      of bed days.

PMID- 21947478
TI  - One-step template-free synthesis of monoporous polymer microspheres with uniform
      sizes via microwave-mediated dispersion polymerization.
AB  - One-step facile synthesis of monoporous polymer microspheres via microwave
      controlled dispersion polymerization is introduced. This template-free method
      employing the dispersion polymerization of styrene under microwave irradiation
      induces directly the formation of uniform monoporous polymer microspheres, with
      controllable morphologies and sizes, which can be tuned by simply adjusting
      parameters for the synthesis. A comparison to conventional heating indicates that
      microwave irradiation plays a vital role in the formation of this novel
      morphology.

PMID- 21947477
TI  - Child abuse rating system for archival information in severe mental illness.
AB  - BACKGROUND: Assessing and addressing child abuse histories are one of the grand
      challenges in psychiatric rehabilitation. Archival information, e.g.,
      comprehensive psychosocial evaluations, objective testing, court documents, and
      medical chart information can provide useful and objective historical accounts.
      It is essential to develop a reliable and valid child abuse rating system for
      archival information. PURPOSE AND METHODS: This study aimed to examine the
      reliability and predictive validity of a highly structured and specific child
      abuse rating system used to code archival information for 150 psychiatric
      inpatients with severe mental illness (SMI). RESULTS: The child abuse rating
      system produced reliable ratings across raters and subtypes of child abuse were
      highly inter-related. More than half (56.5%) of the sample with SMI was
      identified to have one or more types of child abuse history; specifically, child
      sexual abuse (CSA, 36%), child physical abuse (CPA, 27.3%), emotional
      maltreatment (EM, 36%), failure to provide (FTP, 10.7%), and lack of supervision
      (LOS, 32%). Female participants (50%) with SMI had higher rates of CSA than male
      participants (20.8%). Subtypes of child abuse history were related to poorer
      premorbid functioning, but the relationships varied across different types of
      child abuse. In addition, CSA and EM were related to greater
      suspiciousness/hostility. CONCLUSION: The child abuse rating system for archival
      data fills an important gap in existing methodology and, in conjunction with a
      self-report measure, is expected to improve the assessment and understanding of
      the prevalence of child abuse among adults with SMI. Potential limitations and
      recommendations for future research are discussed.

PMID- 21947479
TI  - Methylation and the human brain: towards a new discipline of imaging epigenetics.
AB  - The field of imaging genetics traditionally studies unidirectional associations
      between genes, brain functioning, and behavior. In a recent study by Ursini et
      al. (J Neurosci 31:6692-6698, 2011), imaging genetics methods are combined with
      epigenetic marks in living human beings. This approach may lead to a new field of
      imaging epigenetics, providing more mechanistic insight into causal pathways of
      how gene and environment interact and affect brain development.

PMID- 21947480
TI  - The indeterminate adrenal mass.
AB  - PURPOSE: This paper is a review of the evidence base carried out to provide
      recommendations to aid the clinical management of patients with a CT/MRI-detected
      lipid-poor/indeterminate adrenal mass in whom phaeochromocytoma and metastatic
      adrenal disease are excluded. METHODS: A Medline keyword search of English
      language articles led to the production of a draft document and consensus
      statement containing levels of evidence and grading of recommendations as
      proposed by the Agency for Healthcare Research and Quality. RESULTS: Literature
      review clearly defines the extent and definition of what constitutes a lipid-poor
      adrenal mass. The ability of MRI to better distinguish adrenocortical adenoma
      from adrenocortical cancer is increasing, although there is little high-level
      evidence to confirm this. FDG PET appears promising in its ability to predict
      that an adrenal lesion is benign. CONCLUSIONS: The management of a patient with
      an indeterminate adrenal mass in the absence of clear clinical, biochemical, and
      radiological indications for adrenalectomy may be aided by further assessment
      using chemical-shift/contrast-enhanced MRI and (18)F-FDG PET/CT.

PMID- 21947481
TI  - Percutaneous ultrasound-guided cholangiography using microbubbles to evaluate the
      dilated biliary tract: initial experience.
AB  - OBJECTIVE: To evaluate the feasibility of percutaneous ultrasound cholangiography
      (PUSC) with a microbubble contrast agent in assessing obstructive bile duct
      diseases. METHODS: PUSC and percutaneous transhepatic cholangiography (PTC) were
      performed in 58 patients with obstructive jaundice undergoing ultrasound-guided
      percutaneous transhepatic cholangial drainage (PTCD). The PUSC findings were
      compared with PTC using the Chi-squared test RESULTS: The accuracy of PUSC in
      determining the level of hilar obstruction and extrahepatic obstruction was 100%
      (26/26) and 93.3% (30/32), while the accuracy of PTC was 100% for both (P =
      1.000, P = 0.492, respectively). The accuracy of PUSC in determining the cause of
      hilar obstruction and extrahepatic obstruction was 92.3% (24/26) and 93.8%
      (30/32), respectively, while the accuracy of PTC was 84.6% (22/26) (P = 0.675)
      and 75% (24/34) (P = 0.039), respectively. CONCLUSION: PUSC is comparable to PTC
      in depicting the anatomy of the dilated bile duct tree and determining the level
      of obstruction for patients with obstructive jaundice, hence it expands the
      capacity of ultrasound in evaluating obstructive bile duct disease and simplifies
      the procedure of assessing obstructive jaundice. Key Points * Percutaneous
      ultrasound-guided cholangiography with microbubbles offers a new form of
      cholangiography * PUSC compares well with PTC in evaluating the dilated biliary
      tract. * Radiation is avoided and overall costs may be lower.

PMID- 21947482
TI  - Cardiac MRI: evaluation of phonocardiogram-gated cine imaging for the assessment
      of global und regional left ventricular function in clinical routine.
AB  - OBJECTIVES: To validate a phonocardiogram (PCG)-gated cine imaging approach for
      the assessment of left ventricular (LV) function. METHODS: In this prospective
      study, cine MR imaging of the LV was performed twice in 79 patients by using
      retrospectively PCG- and retrospectively ECG-gated cine SSFP sequences at 1.5 T.
      End-diastolic volumes (EDV), end-systolic volumes (ESV), stroke volumes (SV),
      ejection fraction (EF), muscle mass (MM), as well as regional wall motion were
      assessed. Subgroup analyses were performed for patients with valvular defects and
      for patients with dysrhythmia. RESULTS: PCG-gated imaging was feasible in 75
      (95%) patients, ECG-gating in all patients. Excellent correlations were observed
      for all volumetric parameters (r > 0.98 for all variables analysed). No
      significant differences were observed for EDV (-0.24 +/- 3.14 mL, P = 0.5133),
      ESV (-0.04 +/- 2.36 mL, P = 0.8951), SV (-0.20 +/- 3.41 mL, P = 0.6083), EF (
      0.16 +/- 1.98%, P = 0.4910), or MM (0.31 +/- 4.2 g, P = 0.7067) for the entire
      study cohort, nor for either of the subgroups. PCG- and ECG-gated cine imaging
      revealed similar results for regional wall motion analyses (115 vs. 119 segments
      with wall motion abnormalities, P = 0.3652). CONCLUSION: The present study
      demonstrates that PCG-gated cine imaging enables accurate assessment of global
      and regional LV function in the vast majority of patients in clinical routine.
      KEY POINTS: Phonocardiogram-gating is an alternative to electrocardiographic
      gating in cardiac MR. Phonocardiogram-gated imaging allows reliable assessment of
      global and regional left-ventricular function. Phonocardiogram-gating is feasible
      in patients with valvular lesions or cardiac dysrhythmia. Because phonocardiogram
      gating is insensitive to magneto-hydrodynamic effects, it is suitable for ultra
      high field.

PMID- 21947483
TI  - Obesity-related juvenile form of cartilage lesions: a new affliction in the knees
      of morbidly obese children and adolescents.
AB  - OBJECTIVES: Overweight and obesity are afflictions that lead to an increased risk
      of health problems including joint problems. The aim of the study was to assess
      the condition of articular cartilage in obese adolescent patients suffering from
      knee pain. METHODS: MRI of 24 knees of 20 morbidly obese patients, mean age 14.2
      years, was performed in an open 1.0 Tesla MR system, where the cartilage, the
      quality and structure of the menisci, and the presence or absence of surrounding
      changes was examined. RESULTS: In all patients a cartilage lesion in at least one
      region of the knee could be detected. Retropatellar cartilage lesions have been
      found in 19 knees. Ten cartilage lesions grade I, and four lesions grade II have
      been described in the lateral compartment of the knee, whereas the medial
      compartment showed in eight cases a grade I, in 13 cases a grade II and in two
      cases a grade III cartilage lesion. Meniscal changes were assessed in most
      patients. CONCLUSION: Morbidly obese children and adolescents show major
      abnormalities in the articular cartilage of the knee. Whether obesity alone is
      the causal factor for the development of the pattern of these changes, remains to
      be seen. KEY POINTS: * Morbidly obese children and adolescents often suffer from
      knee pain * Prospective study showed cartilage and meniscal lesions in morbidly
      obese adolescents * MRI is an adequate tool for assessing cartilage lesions even
      in morbidly obese patients * It is unclear whether cartilage abnormalities are
      mainly due to mechanical overload.

PMID- 21947484
TI  - A grid overlay framework for analysis of medical images and its application to
      the measurement of stroke lesions.
AB  - OBJECTIVES: To create and evaluate an interactive software tool for measuring
      imaging data in situations where hand-drawn region-of-interest measurements are
      unfeasible, for example, when the structure of interest is patchy with ill
      defined boundaries. METHODS: An interactive grid overlay software tool was
      implemented that enabled coding of voxels dependent on their imaging appearance
      with a series of user-defined classes. The Grid Analysis Tool (GAT) was designed
      to automatically extract quantitative imaging data, grouping the results by
      tissue class. Inter- and intra-observer reproducibility was evaluated by six
      observers of various backgrounds in a study of acute stroke patients. RESULTS:
      The software tool enabled a more detailed classification of the stroke lesion
      than would be possible with a region-of-interest approach. However, inter
      observer coefficients of variation (CVs) were relatively high, reaching 70% in
      "possibly abnormal" tissue and around 15-20% in normal appearing tissues, while
      intra-observer CVs were no more than 13% in "possibly abnormal" tissue and
      generally less than 1% in normal-appearing tissues. CONCLUSIONS: The grid-overlay
      method overcomes some of the limitations of conventional Region Of Interest (ROI)
      approaches, providing a viable alternative for segmenting patchy lesions with ill
      defined boundaries, but care is required to ensure acceptable reproducibility if
      the method is applied by multiple observers. KEY POINTS: Computer software
      developed to overcome limitations of conventional regions of interest
      measurements * This software is suitable for patchy lesions with ill-defined
      borders * Allows a more detailed assessment of imaging data.

PMID- 21947485
TI  - In vivo imaging of human breast cancer mouse model with high level expression of
      calcium sensing receptor at 3T.
AB  - OBJECTIVES: To demonstrate that manganese can visualise calcium sensing receptor
      (CaSR)-expressing cells in a human breast cancer murine model, as assessed by
      clinical 3T magnetic resonance (MR). METHODS: Human MDA-MB-231-Luc or MCF7-Luc
      breast cancer cells were orthotopically grown in NOD/SCID mice to a minimum mass
      of 5 mm. Mice were evaluated on T1-weighted sequences before and after
      intravenous injection of MnCl(2). To block the CaSR-activated Ca(2+) channels,
      verapamil was injected at the tumour site 5 min before Mn(2+) administration.
      CaSR expression in vivo was studied by immunohistochemistry. RESULTS: Contrast
      enhancement was observed at the tumour periphery 10 min after Mn(2+)
      administration, and further increased up to 40 min. In verapamil-treated mice, no
      contrast enhancement was observed. CaSR was strongly expressed at the tumour
      periphery. CONCLUSION: Manganese enhanced magnetic resonance imaging can
      visualise CaSR-expressing breast cancer cells in vivo, opening up possibilities
      for a new MR contrast agent. KEY POINTS: * Manganese contrast agents helped
      demonstrate breast cancer cells in an animal model. * Enhancement was most marked
      in cells with high calcium sensing receptor expression. * Manganese uptake was
      related to the distribution of CaSR within the tumour. * Manganese MRI may become
      useful to investigate human breast cancer.

PMID- 21947486
TI  - Usefulness of the dynamic gadolinium-enhanced magnetic resonance imaging with
      simultaneous acquisition of coronal and sagittal planes for detection of
      pituitary microadenomas.
AB  - OBJECTIVE: Does dynamic gadolinium-enhanced imaging with simultaneous acquisition
      of coronal and sagittal planes improve diagnostic accuracy of pituitary
      microadenomas compared with coronal images alone? METHODS: Fifty-six patients
      underwent 3-T sella MRI including dynamic simultaneous acquisition of coronal and
      sagittal planes after gadolinium injection. According to conspicuity, lesions
      were divided into four scores (0, no; 1, possible; 2, probable; 3, definite
      delayed enhancing lesion). Additional information on supplementary sagittal
      images compared with coronal ones was evaluated with a 4-point score (0, no; 1,
      possible; 2, probable; 3, definite additional information). Accuracy of tumour
      detection was calculated. RESULTS: Average scores for lesion detection of a
      combination of two planes, coronal, and sagittal images were 2.59, 2.32, and
      2.18. 6/10 lesions negative on coronal images were detected on sagittal ones.
      Accuracy of a combination of two planes, of coronal and of sagittal images was
      92.86%, 82.14% and 75%. Six patients had probable or definite additional
      information on supplementary sagittal images compared with coronal ones alone
      (10.71%). CONCLUSION: Dynamic MRI with combined coronal and sagittal planes was
      more accurate for detection of pituitary microadenomas than routinely used
      coronal images. Simultaneous dynamic enhanced acquisition can make study time
      fast and costs low. KEY POINTS: We present a new dynamic MRI technique for
      evaluating pituitary microadenomas * This technique provides simultaneous
      acquisition of contrast enhanced coronal and sagittal images. * This technique
      makes the diagnosis more accurate and reduces the examination time. * Such MR
      imaging only requires one single bolus of contrast agent.

PMID- 21947487
TI  - MicroRNA-191 targets N-deacetylase/N-sulfotransferase 1 and promotes cell growth
      in human gastric carcinoma cell line MGC803.
AB  - As a family of post-transcriptional regulator of gene expression, the microRNAs
      (miRNAs) control a wide array of biological processes including cell
      differentiation, proliferation and apoptosis, and the dysregulation of miRNAs is
      a hallmark of cancer. Here, we found that the microRNA-191 (miR-191) was at a
      high-expression level in human gastric adenocarcinoma cell line MGC803 and human
      gastric cancer tissues. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide and colony formation assays showed that miR-191 could
      promote cell growth and suppress apoptosis of MGC803 cells. The N-deacetylase/N
      sulfotransferase 1 (NDST1) was confirmed to be a direct target gene of miR-191 by
      enhanced green fluorescent protein reporter experiment. The mRNA and protein
      levels of NDST1 were inversely correlated with miR-191 in MGC803 cells,
      suggesting the negative regulation of NDST1 by miR-191. Furthermore, NDST1 played
      an inhibitory role and could suppress MGC803 cell proliferation. Our findings
      suggested that miR-191 could act as an oncogene in MGC803 cells, and the cellular
      function was partially due to its negative regulation of NDST1.

PMID- 21947488
TI  - Jugular foramen paragangliomas: management, outcome and avoidance of
      complications in a series of 75 cases.
AB  - Jugular foramen paragangliomas are rare skull base tumours posing multiple
      complex diagnostic and management problems. We did a study to evaluate surgical
      technique, outcome and complications in 75 cases of tumours treated by
      multidisciplinary approach (i.e. combined neurosurgery, neuroradiology, ear, nose
      and throat surgery and intensive care unit team). Retrospective study on 75
      consecutive patients with jugular foramen paragangliomas treated surgically from
      1989 to 2005. Preoperative balloon occlusion test was performed in all patients
      as well as embolization (100%). A combined limited infratemporal and
      juxtacondylar approach was used in all patients. Gross total resection was
      achieved in 59 patients (78.7%). The most common complication was represented by
      lower cranial nerve deficits in five patients (6.6%), which was only temporary in
      three. Postoperative facial nerve weakness occurred in five cases (6.6%) and
      resolved in three of them. The remaining two patients underwent facial nerve
      reconstruction by hypoglossal/facial nerve anastomosis. Four patients (5.3%) had
      a postoperative cerebrospinal fluid leak, which was successfully treated by
      lumbar drainage. Two patients (2.7%) died because of complications related to
      surgical injury of lower cranial nerves: one patient developed aspiration
      pneumonia and septicemia and the second one developed a large cervico-bulbar
      hematoma that led to severe respiratory distress and ultimately global cerebral
      hypoxia. Paragangliomas are rare and complex skull base lesions that may be
      managed with low morbidity and mortality if a multidisciplinary approach is
      considered. Facial and lower cranial nerve postoperative deficits can be limited.

PMID- 21947489
TI  - Effect of the Honan intraocular pressure reducer on intraocular pressure increase
      following intravitreal injection using the tunneled scleral technique.
AB  - OBJECTIVE: To determine the effect of the Honan intraocular pressure reducer
      (HIPR) on the rise in intraocular pressure (IOP) after an intravitreal injection
      using a tunneled scleral incision. DESIGN: This was a prospective, comparative,
      controlled, non-randomized clinical study. METHODS: Sixty eyes of 60 patients who
      received intravitreal injections with the tunneled scleral technique were
      allocated into two groups, one with and one without application of the HIPR. The
      pre-operative IOP both before and after application of the HIPR, and the IOP
      immediately postoperative, and at 3 and 10 min postoperatively were evaluated.
      The vitreous reflux was estimated by measuring the large diameter of the sub
      conjunctival bleb formed after intravitreal injection. RESULTS: The pre-operative
      IOP in the HIPR group was significantly lower than that in the non-HIPR group
      following application of the HIPR. The immediate postoperative IOP was
      significantly lower in the HIPR group than in the non-HIPR group. The IOP at 10
      min postoperatively was lower in the HIPR group than in the non-HIPR group. There
      was no difference in the amount of vitreous reflux between the HIPR and the non
      HIPR groups. CONCLUSION: The use of the HIPR reduces the IOP after an
      intravitreal injection using the tunneled scleral technique. However, the HIPR
      does not appear to affect a reduction in the vitreous reflux.

PMID- 21947490
TI  - Perspectives toward oral mucositis prevention from parents and health care
      professionals in pediatric cancer.
AB  - PURPOSE: The objectives of this study were: (1) to describe parents and health
      care professionals (HCPs) perceived importance of oral mucositis prevention in
      children with cancer; (2) To describe utilities and willingness-to-pay (WTP) to
      prevent mucositis. METHODS: Respondents included parents of children receiving
      intensive chemotherapy for leukemia/lymphoma or undergoing stem cell
      transplantation and HCPs caring for children with cancer. Importance of mild and
      severe oral mucositis was estimated using a visual analogue scale (VAS).
      Mucositis-associated utilities were elicited using the time trade-off technique
      (TTO). WTP to avoid mucositis was obtained using contingent valuation. These
      techniques quantify how much time or money the participant is willing to
      relinquish in order to prevent mucositis. RESULTS: Eighty-two parents and 60 HCPs
      were included. Parents and HCPs believed mild mucositis to be of similar
      importance (median VAS 2.5 versus 3.6; P = 0.357) while parents considered severe
      mucositis less important than HCPs (median VAS 8.3 versus 9.0; P < 0.0001). No
      differences in parent versus HCP responses were seen with TTO (mild or severe
      mucositis) and most parents were not willing to trade any survival time to
      prevent severe mucositis. Parents were willing to pay significantly more than
      HCPs to prevent mild mucositis (average median WTP $1,371 CAN vs. $684 CAN, P =
      0.031). No differences were seen in WTP to prevent severe mucositis. CONCLUSIONS:
      Parents and HCP believe severe mucositis to be important, although it is more
      important to HCPs. Parents would not be willing to reduce life expectancy to
      eliminate mucositis.

PMID- 21947491
TI  - Implementation of institutional antiemetic guidelines for low emetic risk
      chemotherapy with docetaxel: a clinical and cost evaluation.
AB  - PURPOSE: The purposes of this study were to evaluate the effect of implementation
      of institutional guidelines for low emetic risk chemotherapy with docetaxel and
      estimate the cost saving for all low emetic risk chemotherapies. METHODS: We
      examined the clinical effect of preparing and implementing institutional
      antiemetic guidelines for the breast cancer patients receiving adjuvant docetaxel
      therapy. Although the antiemetic medication for such patients used to be
      ondansetron 4 mg plus dexamethasone 8 mg (OND + DEX), it was changed to
      dexamethasone (DEX) 12 mg alone after implementation of the institutional
      guidelines. The effectiveness and adverse effects of DEX alone (56 patients, 205
      courses) were compared with those of OND + DEX (41 patients, 151 courses). The
      cost saving was calculated from the antiemetic costs in both groups. The annual
      cost saving was estimated from the number of all low emetic risk chemotherapies
      in a year. RESULTS: The incidences of nausea (19.5% versus 16.1%), vomiting (2.4%
      versus 0%), constipation (34.1% versus 30.4%), and insomnia (17.1% versus 17.9%)
      were not significantly different between the OND + DEX group and DEX alone group.
      In all low emetic risk chemotherapies, US $78,883 of potential cost saving was
      estimated in the first year after changing the antiemetic treatment. CONCLUSION:
      The present results suggest that DEX alone is equally effective for preventing
      nausea and vomiting and less expensive compared with a 5-HT(3) receptor
      antagonist plus DEX in low emetic risk chemotherapy with docetaxel.

PMID- 21947492
TI  - Perception of health and understanding of cardiovascular risk among patients with
      recently diagnosed diabetes and/or metabolic syndrome.
AB  - BACKGROUND: Cardiovascular (CV) disease mortality is increased in diabetes
      mellitus (DM) and metabolic syndrome (MS), conditions which share CV risk
      factors. AIM: The purpose of this study was to assess understanding of CV risk by
      patients with DM and/or MS diagnosed less than 1 year before and seen in primary
      care. Perception by these patients of their health state is also analysed.
      DESIGN: A multicentre, observational study in subjects diagnosed with DM
      diagnosed less than 1 year before and/or with MS, in whom agreement between CV
      risk perceived by patients and assessed by physicians was analysed. METHODS:
      Medical registry data and a survey of health status and perceived risk by
      patients and physicians. Agreement of patient perception of CV risk with
      perception of the physician in charge and with the CV risk established with
      clinical registry data was assessed. Self-perceived health status was also
      studied. RESULTS: A total of 150 physicians recruited 681 patients (71.5% with DM
      and 28.5% with MS) aged 60.8 +/- 10.8 years (55.8% males). Good or excellent
      health were reported by 41.3% and 0.9%, respectively. Inability to give an
      estimate of CV risk was found in 39.8%. Agreement between the CV risks perceived
      by patients and evaluated by chart was poor: kappa index 0.145 (95% CI 0.101
      0.189), p < 0.001. Agreement between CV risk perceived by patients and clinical
      data in the medical registry was weak: kappa index 0.165 (95% CI 0.117-0.213), p
      < 0.001. CONCLUSIONS: Patients with recently diagnosed DM and/or with MS have a
      poor awareness of their CV risk and 42.2% of them think that they have good or
      excellent health.

PMID- 21947493
TI  - Locally advanced mid/low rectal cancer with synchronous liver metastases.
AB  - BACKGROUND: Management of patients with T3/4 and/or N+ mid/low rectal cancer with
      synchronous liver metastases is not codified. The aim of this study was to
      analyze outcomes of our approach which consists of neoadjuvant chemotherapy or
      chemoradiotherapy, according to liver disease extension, followed by simultaneous
      rectal and liver resection. METHODS: Between 2000 and 2009, 354 patients
      underwent hepatectomy for synchronous metastases. Thirty-six consecutive patients
      who underwent rectal and liver resection for metastatic T3/4 and/or N+ mid/low
      rectal cancer were analyzed. RESULTS: Liver metastases were multiple in 27
      patients, bilobar in 22, and >5 cm in six. Up-front treatment was chemotherapy in
      15 patients, chemoradiotherapy in seven, chemotherapy followed by
      chemoradiotherapy in six, and surgery in eight (five symptomatic tumors). After
      chemotherapy alone (median number of cycles = 6), primary tumor response was
      observed in 11 patients (three complete responses). After chemoradiotherapy, only
      one patient had liver disease progression. Eighty-nine percent of patients
      underwent simultaneous rectal and hepatic resection. Mortality and morbidity
      rates were 2.8% (one pulmonary embolism) and 36%, respectively. After a mean
      follow-up of 39 months, 5-year overall and disease-free survival were 59.3 and
      39.6%, respectively. Twenty-one patients had recurrence, including three pelvic
      recurrences (8.3%). No pelvic recurrence occurred among patients who correctly
      completed treatment strategy. All patients who received neoadjuvant
      chemoradiotherapy were alive and disease-free; 5-year overall and disease-free
      survival of patients receiving neoadjuvant chemotherapy were 59.3 and 25%,
      respectively. CONCLUSIONS: For patients with metastatic T3/4 and/or N+ mid/low
      rectal cancer, the present strategy was safe and effective. Good disease control
      was achieved by neoadjuvant treatments, low morbidity rates were associated with
      simultaneous resection, and excellent long-term outcomes with low local relapse
      rate were obtained.

PMID- 21947495
TI  - Fast-track concepts in major open upper abdominal and thoracoabdominal surgery: a
      review.

PMID- 21947494
TI  - Robotic versus open pancreaticoduodenectomy: a comparative study at a single
      institution.
AB  - BACKGROUND: Minimally invasive pancreaticoduodenectomy (PD) remains one of the
      most challenging abdominal procedures, and its application is poorly reported in
      the literature so far. To date, few data are available comparing a minimally
      invasive approach to open PD. The aim of the present study is to compare the
      robotic and open approaches for PD at a single institution. METHODS: Data from 83
      consecutive PD procedures performed between January 2002 and May 2010 at a single
      institution were retrospectively reviewed. Patients were stratified into two
      groups: the open group (n = 39; 47%) and the robotic group (n = 44; 53%).
      RESULTS: Patients in the robotic group were statistically older (63 years of age
      versus 56 years; p = 0.04) and heavier (body mass index: 27.7 vs. 24.8; p =
      0.01); and had a higher American Society of Anesthesiologists (ASA) score (2.5
      vs. 2.15; p = 0.01) when compared to the open group. Indications for surgery were
      the same in both groups. The robotic group had a significantly shorter operative
      time (444 vs. 559 min; p = 0.0001), reduced blood loss (387 vs. 827 ml; p =
      0.0001), and a higher number of lymph nodes harvested (16.8 vs. 11; p = 0.02)
      compared to the open group. There was no significant difference between the two
      groups in terms of complication rates, mortality rates, and hospital stay.
      CONCLUSIONS: The authors present one of the first studies comparing open and
      robotic PD. While it is too early to draw definitive conclusions concerning the
      long-term outcomes, short-term results show a positive trend in favor of the
      robotic approach without compromising the oncological principles associated with
      the open approach.

PMID- 21947496
TI  - Well-informed foraging: damage-released chemical cues of injured prey signal
      quality and size to predators.
AB  - Predators use a variety of information sources to locate potential prey, and
      likewise prey animals use numerous sources of information to detect and avoid
      becoming the meal of a potential predator. In freshwater environments,
      chemosensory cues often play a crucial role in such predator/prey interactions.
      The importance of chemosensory information to teleost fish in marine environments
      is not well understood. Here, we tested whether coral reef fish predators are
      attracted to damage-released chemical cues from already wounded prey in order to
      find patches of prey and minimize their own costs of obtaining food. Furthermore,
      we tested if these chemical cues would convey information about status of the
      prey. Using y-maze experiments, we found that predatory dottybacks, Pseudochromis
      fuscus, were more attracted to skin extracts of damselfish, Pomacentrus
      amboinensis, prey that were in good condition compared to prey in poor body
      condition. Moreover, in both the laboratory and field, we found that predators
      could differentiate between skin extracts from prey based on prey size, showing a
      greater attraction to extracts made from prey that were the appropriate size to
      consume. This suggests that predators are not attracted to any general substance
      released from an injured prey fish instead being capable of detecting and
      distinguishing relatively small differences in the chemical composition of the
      skin of their prey. These results have implications for understanding predator
      foraging strategies and highlights that chemical cues play a complex role in
      predator-prey interactions in marine fish.

PMID- 21947497
TI  - Commentary: Do we have a consistent terminology for species diversity? The
      fallacy of true diversity.
AB  - There is no single best index that can be used to answer all questions about
      species diversity. Entropy-based diversity indices, including Hill's indices,
      cannot account for geographical and phylogenetic structure. While a single
      diversity index arises if we impose several constraints-most notably that gamma
      diversity be completely decomposed into alpha and beta diversity-there are many
      ecological questions regarding species diversity for which it is
      counterproductive, requiring decomposability. Non-decomposable components of
      gamma diversity may quantify important intrinsic ecological properties, such as
      resilience or nestedness.

PMID- 21947500
TI  - Persistence of cypermethrin and decamethrin residues in/on brinjal fruits.
AB  - Residues of cypermethrin and decamethrin were estimated in brinjal fruits by gas
      liquid chromatography following single application of Cymbush 25 EC @ 43.75 and
      87.50 g a.i./ha and of Decis 2.8 EC @ 11.20 and 22.40 g a.i./ha at fruiting
      stage. The average initial deposits of cypermethrin 0.600 and 1.095 mg kg(-1) and
      of decamethrin 0.430 and 0.900 mg kg(-1) were observed for single and double
      dose, respectively. Residues reached below maximum residue limit (MRL) value of
      0.2 and 0.05 mg kg(-1) on third and seventh day for cypermethrin and decamethrin,
      respectively. The half-life values (t(1/2)) were worked out to be 1.16, 1.18 days
      for cypermethrin and 1.33, 1.42 days for decamethrin at single and double dose,
      respectively following first order kinetics. Washing and washing followed by
      boiling/cooking processes were found to be effective in reducing the residues of
      both the insecticides in brinjal fruits. Maximum reduction (31-42%) and (26-37%)
      was observed by washing followed by boiling/cooking for cypermethrin and
      decamethrin, respectively.

PMID- 21947499
TI  - Voltage-gated sodium channel-associated proteins and alternative mechanisms of
      inactivation and block.
AB  - Voltage-gated sodium channels mediate inward current of action potentials upon
      membrane depolarization of excitable cells. The initial transient sodium current
      is restricted to milliseconds through three distinct channel-inactivating and
      blocking mechanisms. All pore-forming alpha subunits of sodium channels possess
      structural elements mediating fast inactivation upon depolarization and recovery
      within milliseconds upon membrane repolarization. Accessory subunits modulate
      fast inactivation dynamics, but these proteins can also limit current by
      contributing distinct inactivation and blocking particles. A-type isoforms of
      fibroblast growth factor homologous factors (FHFs) bear a particle that induces
      long-term channel inactivation, while sodium channel subunit Navbeta4 employs a
      blocking particle that rapidly dissociates upon membrane repolarization to
      generate resurgent current. Despite their different physiological functions, the
      FHF and Navbeta4 particles have similarity in amino acid composition and
      mechanisms for docking within sodium channels. The three competing channel
      inactivating and blocking processes functionally interact to regulate a neuron's
      intrinsic excitability.

PMID- 21947501
TI  - Hormetic responses of a stinkbug predator to sublethal doses of pyrethroid.
AB  - Stressors can affect reproduction and longevity by impacting endocrine and immune
      systems but they may increase life span and stimulate reproduction. The effects
      of sublethal doses of permethrin topically applied on third instar nymphs of
      Podisus distinctus (Heteroptera: Pentatomidae) was evaluated. The weight of
      females survival of nymph and adults, number of eggs and nymphs/females of P.
      distinctus were higher when exposed to lower doses of permethrin. On the other
      hand, the exposition to the 0.131, 1.315 and 13.15 ppb showed positive effects on
      the oviposition periods, number of egg masses and longevity of P. distinctus
      females.

PMID- 21947502
TI  - Effects of dietary methylmercury on the zebrafish brain: histological,
      mitochondrial, and gene transcription analyses.
AB  - The neurotoxic compound methylmercury (MeHg) is a commonly encountered pollutant
      in the environment, and constitutes a hazard for wildlife and human health
      through fish consumption. To study the neurotoxic impact of MeHg on piscivorous
      fish, we contaminated the model fish species Danio rerio for 25 and 50 days with
      food containing 13.5 MUg/g dry weight (dw) of MeHg (0.6 MUg MeHg/fish/day), an
      environmentally relevant dose leading to brain mercury concentrations of 30 +/- 4
      MUg of Hg g(-1) (dw) after 25 days of exposure and 46 +/- 7 MUg of Hg g(-1) (dw)
      after 50 days. Brain mitochondrial respiration was not modified by exposure to
      MeHg, contrary to what happens in skeletal muscles. A 6-fold increase in the
      expression of the sdh gene encoding the succinate dehydrogenase Fe/S protein
      subunit was detected in the contaminated brain after 50 days of exposure. An up
      regulation of 3 genes, atp2b3a, atp2b3b, and slc8a2b, encoding for calcium
      transporters was noticed after 25 days of exposure but the atp2b3a and atp2b3b
      were repressed and the slc8a2b gene expression returned to its basal level after
      50 days, suggesting a perturbation of calcium homeostasis. After 50 days, we
      detected the up regulation of glial fibrillary acidic protein and glutathione S
      transferase genes (gfap and gst), along with a repression of the glutathione
      peroxidase gene gpx1. These results match well with a MeHg-induced onset of
      oxidative stress and inflammation. A transmission electron microscopic
      observation confirmed an impairment of the optical tectum integrity, with a
      decrease of the nucleal area in contaminated granular cells compared to control
      cells, and a lower density of cells in the contaminated tissue. A potential
      functional significance of such changes observed in optical tectum when
      considering wild fish contaminated in their natural habitat might be an impaired
      vision and therefore a lowered adaptability to their environment.

PMID- 21947498
TI  - Cyclic nucleotide-dependent relaxation pathways in vascular smooth muscle.
AB  - Vascular smooth muscle tone is controlled by a balance between the cellular
      signaling pathways that mediate the generation of force (vasoconstriction) and
      release of force (vasodilation). The initiation of force is associated with
      increases in intracellular calcium concentrations, activation of myosin light
      chain kinase, increases in the phosphorylation of the regulatory myosin light
      chains, and actin-myosin crossbridge cycling. There are, however, several
      signaling pathways modulating Ca(2+) mobilization and Ca(2+) sensitivity of the
      contractile machinery that secondarily regulate the contractile response of
      vascular smooth muscle to receptor agonists. Among these regulatory mechanisms
      involved in the physiological regulation of vascular tone are the cyclic
      nucleotides (cAMP and cGMP), which are considered the main messengers that
      mediate vasodilation under physiological conditions. At least four distinct
      mechanisms are currently thought to be involved in the vasodilator effect of
      cyclic nucleotides and their dependent protein kinases: (1) the decrease in
      cytosolic calcium concentration ([Ca(2+)]c), (2) the hyperpolarization of the
      smooth muscle cell membrane potential, (3) the reduction in the sensitivity of
      the contractile machinery by decreasing the [Ca(2+)]c sensitivity of myosin light
      chain phosphorylation, and (4) the reduction in the sensitivity of the
      contractile machinery by uncoupling contraction from myosin light-chain
      phosphorylation. This review focuses on each of these mechanisms involved in
      cyclic nucleotide-dependent relaxation of vascular smooth muscle under
      physiological conditions.

PMID- 21947503
TI  - Production, characterisation and applications of monoclonal antibodies to two
      novel porcine bocaviruses from swine in Northern Ireland.
AB  - The production, preliminary characterisation and applications of monoclonal
      antibodies (mAbs) against two novel swine bocaviruses isolated in cell culture
      from swine in Northern Ireland are described. Of the 17 stable final clones
      produced, four were characterised. All were of the IgG2a isotype and showed no
      cross-reactivity with either bocavirus strain. Partial neutralisation was
      observed with PBoV4 mAbs and homologous virus. The two mAbs selected for use in
      antigen-detecting ELISAs were successful in highlighting those fractions
      containing infectious virus within sucrose gradients. This is the first report of
      the production of specific reagents that will prove useful in the study of the
      biology of these viruses and swine bocavirus-associated diseases.

PMID- 21947504
TI  - Investigations on the RNA binding and phosphorylation of groundnut bud necrosis
      virus nucleocapsid protein.
AB  - Groundnut bud necrosis virus belongs to the genus Tospovirus, infects a wide
      range of crop plants and causes severe losses. To understand the role of the
      nucleocapsid protein in the viral life cycle, the protein was overexpressed in E.
      coli and purified by Ni-NTA chromatography. The purified N protein was well
      folded and was predominantly alpha-helical. Deletion analysis revealed that the C
      terminal unfolded region of the N protein was involved in RNA binding.
      Furthermore, the N protein could be phosphorylated in vitro by Nicotiana
      benthamiana plant sap and by purified recombinant kinases such as protein kinase
      CK2 and calcium-dependent protein kinase. This is the first report of
      phoshphorylation of a nucleocapsid protein in the family Bunyaviridae. The
      possible implications of the present findings for the viral life cycle are
      discussed.

PMID- 21947505
TI  - High-temperature-mediated spontaneous mutations in the coat protein of cucumber
      mosaic virus in Nicotiana tabacum.
AB  - Since temperature effects on cucumber mosaic virus (CMV) have not been
      extensively studied, we examined the effects of a moderate increase in
      temperature on the virulence and the genetic diversity of CMV in Nicotiana
      tabacum (cv. Samsun NN). Two passage lines were initiated by inoculation of
      tobacco plants with a chlorosis strain of CMV (designated FFM-CMV) derived from
      full-length infectious CMV clones. Symptom changes in the tobacco plants were
      monitored during five successive passages at 25 and 33 degrees C. At the fifth
      passage, tobacco plants inoculated with FFM-CMV at 33 degrees C showed typical
      chlorosis symptoms at 7 days post-inoculation (dpi), and the plants further
      developed mosaic symptoms on the upper leaves at 20 dpi. In contrast, tobacco
      plants inoculated with FFM-CMV at 25 degrees C did not show changes in symptoms
      on the upper leaves within 20 days. Sequence analysis of the coat protein (CP)
      genes of FFM-CMV revealed that a variety of spontaneous sequence changes were
      generated from the 14th and the 18th leaves of 33 degrees C lineage tobacco
      plants, but not from those of 25 degrees C lineage tobacco plants. The major CP
      mutation from the upper leaves of 33 degrees C lineage tobacco plants was an
      L129P mutation, indicating a change in symptoms correlating to the population
      composition of the mutant viruses. Although relatively low mutation rates were
      observed from 33 degrees C-lineage tobacco plants, some CP mutations may have
      been selected for systemic movement of CMV at the higher temperature, providing
      evidence for the importance of temperature in the process of genetic
      diversification of CMV populations.

PMID- 21947506
TI  - Partial inactivation of CCR5- and CXCR4- tropic HIV-1 by human urine.
AB  - Human urine has been poorly investigated with regard to infection with human
      immunodeficiency virus (HIV). Here, we have studied the anti-infective functional
      properties of human urine against HIV. The effect of fresh urine pools on CCR5-
      and CXCR4-tropic HIV-1 was evaluated by using four in vitro mucosal models:
      reduction of infectivity of urine-treated HIV-1 particles, HIV-1 attachment to
      immature monocyte-derived dendritic cells (iMDDC), transfer of HIV-1 particles
      from iMDDC to autologous CD4 T cells, and HIV-1 transcytosis through epithelial
      cells. Human urine partially disrupted both CCR5- and CXCR4-tropic HIV-1
      particles, moderately decreased the adsorption of HIV-1 on dendritic cells, and
      partially decreased the transfer of HIV-1 particles from dendritic cells to
      autologous T cells. These findings demonstrate partial inactivation of HIV
      infectivity and suggest that voiding urine after coitus could play a potential
      role in reducing the risk of HIV infection by both mechanically flushing out and
      neutralizing the infectivity of HIV-1 particles present in the genital tract.

PMID- 21947507
TI  - STD-NMR: application to transient interactions between biomolecules-a
      quantitative approach.
AB  - Saturation transfer difference NMR (STD NMR) spectroscopy is one of the most
      powerful NMR techniques for detection and characterization of transient (fast)
      receptor-ligand interactions in solution. By observing the signals of a small
      molecule (ligand) with spectroscopic properties suitable for high-resolution
      studies, irrespective of receptor size, STD NMR enables quantitative structural
      and affinity information to be obtained about the molecular recognition process
      under study. Approximately one decade after its introduction, the technique has
      reached maturity, and is highly robust and useful. The objective of this article
      is to review the current status of this powerful technique, with particular
      emphasis on quantitative applications, within the framework of the (bio
      )chemistry of molecular recognition.

PMID- 21947508
TI  - Influence of the electric field on supramolecular structure and properties of
      amyloid-specific reagent Congo red.
AB  - Among specific amyloid ligands, Congo red and its analogues are often considered
      potential therapeutic compounds. However, the results of the studies so far have
      not been univocal because the properties of this dye, derived mostly from its
      supramolecular nature, are still poorly understood. The supramolecular structure
      of Congo red, formed by pi-pi stacking of dye molecules, is susceptible to the
      influence of the electric field, which may significantly facilitate electron
      delocalization. Consequently, the electric field may generate altered physico
      chemical properties of the dye. Enhanced electron delocalization, induced by the
      electric field, alters the total charge of Congo red, making the dye more acidic
      (negatively charged). This is a consequence of withdrawing electrons from polar
      substituents of aromatic rings-sulfonic and amino groups-thus increasing their
      tendency to dissociate protons. The electric field-induced charge alteration
      observed in electrophoresis depends on dye concentration. This concentration
      dependent charge alteration effect disappears when the supramolecular structure
      disintegrates in DMSO. Dipoles formed from supramolecular fibrillar species in
      the electric field become ordered in the solution, introducing the modified
      arrangement to liquid crystalline phase. Experimental results and theoretical
      studies provide evidence confirming predictions that the supramolecular character
      of Congo red is the main reason for its specific properties and reactivity.

PMID- 21947509
TI  - A simple procedure to evaluate the efficiency of bio-macromolecular rigid-body
      refinement by small-angle scattering.
AB  - A simple and rapid procedure is presented that enables evaluation and
      visualization of refinement efficiency for bio-macromolecular complexes
      consisting of two subunits in a given orientation by using small-angle
      scattering. Subunit orientations within a complex can be provided in practice by
      NMR residual dipolar couplings, an approach that has been combined with
      increasing success to complement small-angle data. The procedure is illustrated
      by applying it to several systems composed of two simple geometric bodies
      (ellipsoids) and to protein complexes from the protein data bank that vary in
      subunit size and anisometry. The effects of the experimental small-angle
      scattering range (Q-range) and data noise level on the refinement efficiency are
      investigated and discussed. The procedure can be used in two ways: (1) either as
      a quick preliminary test to probe the refinement capacity expected for a given
      bio-macromolecular complex prior to sophisticated and time-consuming experiments
      and data analysis, or (2) as an a posteriori check of the stability and accuracy
      of a refined model and for illustration of the residual degrees of freedom of the
      subunit positions that are in agreement with both small-angle data and restraints
      on subunit orientation (as provided, e.g., by NMR).

PMID- 21947510
TI  - Adrenocortical carcinoma: which surgical approach?
AB  - INTRODUCTION: There are no randomised studies comparing open and laparoscopic
      approaches foradrenalectomy in patients with adrenal cortical carcinoma. METHODS:
      There is evidence of postoperative benefit for the patients undergoing
      laparoscopic adrenalectomy compared to open adrenalectomy (level B). RESULTS:
      Results from comparison of oncological outcomes in ACC between open and
      laparoscopic approaches are equivocal: increasedrisk of local recurrence and
      peritoneal carcinomatosis by the laparoscopic route (level D), and identical
      results between the two approaches in terms of survival, recurrence and
      peritoneal carcinomatosis (level C). CONCLUSION: An open approach is recommended
      in case of local invasion, with a view to achieving an R0 resection (level D).
      Laparoscopic resection of ACC/potentially malignant tumours, which includes
      removal of surrounding periadrenal fat and results in an R0 resection without
      tumour capsule rupture, may be performed for preoperative and intraoperative
      stage 1-2 ACC and tumours with a diameter < 10 cm (level C).

PMID- 21947511
TI  - Measuring the stigma of psychiatry and psychiatrists: development of a
      questionnaire.
AB  - The stigma of mental illness is a severe burden for people suffering from mental
      illness both in private and public life, also affecting their relatives, their
      close social network, and the mental health care system in terms of disciplines,
      providers, and institutions. Interventions against the stigma of mental illness
      employ complementary strategies (e.g., protest, education, and contact) and
      address different target groups (e.g., school children and teachers, journalists,
      stakeholders). Within this framework, the World Psychiatric Association has
      adopted an Action Plan with the goal to improve the image of psychiatry and to
      reduce potential stigmatizing attitudes toward psychiatry and psychiatrists. To
      evaluate such interventions, a questionnaire has been developed that assesses
      opinions and attitudes toward psychiatrists and psychiatry in different samples
      of medical specialists (psychiatrists and general practitioners). The
      questionnaire comprises scales about perceived stigma in terms of the perception
      of societal stereotypes, self-stigma in terms of stereotype agreement, perceived
      stigma in terms of structural discriminations, discrimination experiences, stigma
      outcomes, and attitudes toward a second medical discipline. It is available in
      several languages (Arab, English, German, Japanese, Polish, and Spanish) and can
      easily be adapted for utilization in other medical specialties.

PMID- 21947512
TI  - Diagnostic performance of a Near-Infrared Breast Imaging system as adjunct to
      mammography versus X-ray mammography alone.
AB  - OBJECTIVES: Radiologist reader performance for breast cancer detection using
      mammography plus Near-Infrared Breast Imaging (NIBI) was compared with
      mammography alone. METHODS: Two hundred seventy-six consecutive patients with
      suspected breast lesions underwent both mammography and NIBI. Four blinded
      radiologists independently first reviewed the mammograms alone. Readers
      subsequently reviewed the mammograms in combination with NIBI. The diagnostic
      benefit of NIBI as an adjunct to mammography was determined by performing
      receiver operating characteristics (ROC) analyses for each reader based on BI
      RADS categories (Breast Imaging Reporting and Data System) and LOS (level of
      suspicion) scores. Additionally, a multireader-multicase (ROC) analysis of
      variance (ANOVA) was carried out. RESULTS: For the LOS-based analysis, the
      combination of mammography and NIBI resulted in a slightly larger area under the
      curve (AUC) for all four readers. The analysis based on BI-RADS categories also
      demonstrated a slight increase in AUC for three readers for the combination of
      mammography and NIBI compared with mammography alone. For the fourth reader, AUC
      was smaller for the combination compared with mammography alone. Neither for the
      separate ROC-analyses nor for the ANOVA, significant differences between the two
      methods were obtained. CONCLUSIONS: The combination of mammography and NIBI did
      not perform significantly better than mammography alone. KEY POINTS: The
      intrinsic contrast provided by optical breast imaging may be inadequate We found
      slightly (but nonsignificant) higher accuracy for optical imaging and mammography
      compared with mammography alone. Contrast agents might be necessary to improve
      the performance of optical breast imaging.

PMID- 21947514
TI  - Temporo-spatial model construction using the MML and software framework.
AB  - Development of complex temporo-spatial biological computational models can be a
      time consuming and arduous task. These models may contain hundreds of
      differential equations as well as realistic geometries that may require
      considerable investment in time to ensure that all model components are correctly
      implemented and error free. To tackle this problem, the Modeling Markup Languages
      (MML) and software framework is a modular XML/HDF5-based specification and
      toolkits that aims to simplify this process. The main goal of this framework is
      to encourage reusability, sharing and storage. To achieve this, the MML framework
      utilizes the CellML specification and repository, which comprises an extensive
      range of curated models available for use. The MML framework is an open-source
      project available at http://mml.gsbme.unsw.edu.au.

PMID- 21947513
TI  - Diagnostic performance of state-of-the-art imaging techniques for morphological
      assessment of vascular abnormalities in patients with chronic thromboembolic
      pulmonary hypertension (CTEPH).
AB  - OBJECTIVES: To determine the most comprehensive imaging technique for the
      assessment of pulmonary arteries in patients with chronic thromboembolic
      pulmonary hypertension (CTEPH). METHODS: 24 patients with CTEPH were examined by
      ECG-gated multi-detector CT angiography (MD-CTA), contrast-enhanced MR
      angiography (ce-MRA) and selective digital subtraction angiography (DSA) within 3
      days. Two readers in consensus separately evaluated each imaging technique (48
      main, 144 lobar and 449 segmental arteries) for typical changes like complete
      obstructions, vessel cut-offs, intimal irregularities, incorporated thrombus
      formations, and bands and webs. A joint interpretation of all three techniques
      served as a reference standard. RESULTS: Based on image quality, there was no non
      diagnostic examination by either imaging technique. DSA did not sufficiently
      display 1 main, 3 lobar and 4 segmental arteries. The pulmonary trunk was not
      assessable by DSA. One patient showed thrombotic material at this level only by
      MD-CTA and MRA. Sensitivity and specificity of MD-CTA regarding CTEPH-related
      changes at the main/lobar and at the segmental levels were 100%/100% and
      100%/99%, of ce-MRA 83.1%/98.6% and 87.7%/98.1%, and of DSA 65.7%/100% and
      75.8%/100%, respectively. CONCLUSION: ECG-gated MD-CTA proved the most adequate
      technique for assessment of the pulmonary arteries in the diagnostic work-up of
      CTEPH patients. KEY POINTS: * A prospective single-centre study evaluated ECG
      gated MDCTA, ce-MRA and DSA in CTEPH patients. * ECG-gated MD-CT angiography
      outperformed DSA and ce-MRA. * Right heart catheterisation should be reserved
      only for assessment of pulmonary haemodynamics.

PMID- 21947515
TI  - Monopolar electrosurgical thermal management for minimizing tissue damage.
AB  - In this study, a novel thermal management system (TMS) is developed for the
      minimization of thermal spread created by a monopolar electrosurgical device, the
      most commonly used surgical instrument. The phenomenon of resistive heating of
      tissue is modeled using the finite-element method (FEM) to analyze the electrical
      potential and temperature distributions in biological tissue subjected to heat
      generation during monopolar electrosurgery. Ex vivo experiments are used to
      validate the FEM by comparing the model predicted and experimentally measured
      temperatures. The predicted FEM maximum temperature 1.0 m adjacent to the
      electrode is within 1% of the experimentally measured maximum temperature using a
      standard monopolar pencil electrode. A TMS consisting of adjacent cooling
      channels produces coagulation volumes 80% that of standard monopolar procedures
      while maintaining comparable temperatures in the targeted tissue below the
      electrode. In vivo temperatures using a device incorporating a TMS at distances
      of 2 and 3 m adjacent to the electrode edge are maintained below temperatures
      known to damage tissue.

PMID- 21947516
TI  - Integrative, multimodal analysis of glioblastoma using TCGA molecular data,
      pathology images, and clinical outcomes.
AB  - Multimodal, multiscale data synthesis is becoming increasingly critical for
      successful translational biomedical research. In this letter, we present a large
      scale investigative initiative on glioblastoma, a high-grade brain tumor, with
      complementary data types using in silico approaches. We integrate and analyze
      data from The Cancer Genome Atlas Project on glioblastoma that includes novel
      nuclear phenotypic data derived from microscopic slides, genotypic signatures
      described by transcriptional class and genetic alterations, and clinical outcomes
      defined by response to therapy and patient survival. Our preliminary results
      demonstrate numerous clinically and biologically significant correlations across
      multiple data types, revealing the power of in silico multimodal data integration
      for cancer research.

PMID- 21947517
TI  - Measurement of fractional order model parameters of respiratory mechanical
      impedance in total liquid ventilation.
AB  - This study presents a methodology for applying the forced-oscillation technique
      in total liquid ventilation. It mainly consists of applying sinusoidal volumetric
      excitation to the respiratory system, and determining the transfer function
      between the delivered flow rate and resulting airway pressure. The investigated
      frequency range was f ? [0.05, 4] Hz at a constant flow amplitude of 7.5 mL/s.
      The five parameters of a fractional order lung model, the existing "5-parameter
      constant-phase model," were identified based on measured impedance spectra. The
      identification method was validated in silico on computer-generated datasets and
      the overall process was validated in vitro on a simplified single-compartment
      mechanical lung model. In vivo data on ten newborn lambs suggested the
      appropriateness of a fractional-order compliance term to the mechanical impedance
      to describe the low-frequency behavior of the lung, but did not demonstrate the
      relevance of a fractional-order inertance term. Typical respiratory system
      frequency response is presented together with statistical data of the measured in
      vivo impedance model parameters. This information will be useful for both the
      design of a robust pressure controller for total liquid ventilators and the
      monitoring of the patient's respiratory parameters during total liquid
      ventilation treatment.

PMID- 21947518
TI  - Therapeutic effect of Saraca asoca (Roxb.) Wilde on lysosomal enzymes and
      collagen metabolism in adjuvant induced arthritis.
AB  - Rheumatoid arthritis is a chronic, progressive and systemic inflammatory disorder
      mainly affecting the synovial joints. In the present study, we evaluated the anti
      arthritic effect of the methanol extract of Saraca asoca (Roxb.) Wilde.,
      (Fabaceae) on adjuvant induced arthritis by assessing paw swelling, body weight,
      the levels of lysosomal enzymes, protein bound carbohydrates, serum cytokines,
      urinary collagen and histopathology of joints. It was found that S. asoca
      methanol extract at doses of 50, 100 and 200 mg/kg reduced the paw thickness and
      elevated the mean body weight of arthritic rats. The treatment of S. asoca showed
      a significant reduction in the levels of both plasma and liver lysosomal enzymes.
      The protein bound carbohydrates and urinary collagen contents were also decreased
      at a significant level by the treatment of S. asoca methanol extract. The
      histopathological study of the joints showed the anti-arthritic property of S.
      asoca which nearly normalized the histological architecture of the joints.
      Further, we established the anti-arthritic activity of S. asoca methanol extract
      by measuring the levels of cytokines in both arthritic and treated rats. The
      treatment of S. asoca reduced the levels of pro-inflammatory cytokines. In
      conclusion, S. asoca methanol extract was capable of ameliorating the conditions
      of arthritis in adjuvant induced arthritic rats.

PMID- 21947520
TI  - Automatic construction of parts+geometry models for initializing groupwise
      registration.
AB  - Groupwise nonrigid image registration is a powerful tool to automatically
      establish correspondences across sets of images. Such correspondences are widely
      used for constructing statistical models of shape and appearance. As existing
      techniques usually treat registration as an optimization problem, a good
      initialization is required. Although the standard initialization-affine
      transformation-generally works well, it is often inadequate when registering
      images of complex structures. In this paper we present a more sophisticated
      method that uses the sparse matches of a parts+geometry model as the
      initialization. We show that both the model and its matches can be automatically
      obtained, and that the matches are able to effectively initialize a groupwise
      nonrigid registration algorithm, leading to accurate dense correspondences. We
      also show that the dense mesh models constructed during the groupwise
      registration process can be used to accurately annotate new images. We
      demonstrate the efficacy of the approach on three datasets of increasing
      difficulty, and report on a detailed quantitative evaluation of its performance.

PMID- 21947521
TI  - Bayesian texture classification based on contourlet transform and BYY harmony
      learning of Poisson mixtures.
AB  - As a newly developed 2-D extension of the wavelet transform using multiscale and
      directional filter banks, the contourlet transform can effectively capture the
      intrinsic geometric structures and smooth contours of a texture image that are
      the dominant features for texture classification. In this paper, we propose a
      novel Bayesian texture classifier based on the adaptive model-selection learning
      of Poisson mixtures on the contourlet features of texture images. The adaptive
      model-selection learning of Poisson mixtures is carried out by the recently
      established adaptive gradient Bayesian Ying-Yang harmony learning algorithm for
      Poisson mixtures. It is demonstrated by the experiments that our proposed
      Bayesian classifier significantly improves the texture classification accuracy in
      comparison with several current state-of-the-art texture classification
      approaches.

PMID- 21947522
TI  - Outdoor scene image segmentation based on background recognition and perceptual
      organization.
AB  - In this paper, we propose a novel outdoor scene image segmentation algorithm
      based on background recognition and perceptual organization. We recognize the
      background objects such as the sky, the ground, and vegetation based on the color
      and texture information. For the structurally challenging objects, which usually
      consist of multiple constituent parts, we developed a perceptual organization
      model that can capture the nonaccidental structural relationships among the
      constituent parts of the structured objects and, hence, group them together
      accordingly without depending on a priori knowledge of the specific objects. Our
      experimental results show that our proposed method outperformed two state-of-the
      art image segmentation approaches on two challenging outdoor databases (Gould
      data set and Berkeley segmentation data set) and achieved accurate segmentation
      quality on various outdoor natural scene environments.

PMID- 21947519
TI  - Prevention and treatment of Schistosoma mansoni-induced liver fibrosis in mice.
AB  - The present study was designed to examine the potential preventive and curative
      effects of curcumin, resveratrol, imatinib, rosiglitazone, losartan and bosentan
      (BOS) on Schistosoma mansoni-induced liver fibrosis in mice. Induction of liver
      fibrosis was produced in male Swiss mice by subcutaneous injection of S. mansoni
      cercariae per mouse. Mice were left for 28 days before starting the experiment
      then mice were divided into two main groups. The first group was further
      subdivided into experimental groups and started drug treatment at day 28 after
      infection and continued for 2 weeks in order to evaluate the potential preventive
      effects of the mentioned drugs on S. mansoni-induced liver fibrosis. The second
      group of mice were left for 2 weeks and then treated with praziquantel for two
      consecutive days to eradicate the worms and so stop egg disposition and further
      fibrosis development. Mice were then subdivided into the experimental groups and
      drug treatment was started for 2 weeks to evaluate their efficacy to decrease the
      developed fibrosis. At the end of the experiment period, mice were killed and
      serum was collected for the estimation of alanine aminotransferase (ALT),
      aspartate aminotransferase (AST), bilirubin and albumin. Liver tissue was taken
      for the estimation of hepatic hydroxyproline content and histopathological
      examination to confirm the biochemical results. Results of the study indicate
      that curcumin and imatinib have potent antifibrotic activity both in suppressing
      and reversing S. mansoni-induced liver fibrosis, while resveratrol has beneficial
      effects only in suppressing the development of S. mansoni-induced liver fibrosis.

PMID- 21947523
TI  - Completely automated multiresolution edge snapper--a new technique for an
      accurate carotid ultrasound IMT measurement: clinical validation and benchmarking
      on a multi-institutional database.
AB  - The aim of this paper is to describe a novel and completely automated technique
      for carotid artery (CA) recognition, far (distal) wall segmentation, and intima
      media thickness (IMT) measurement, which is a strong clinical tool for risk
      assessment for cardiovascular diseases. The architecture of completely automated
      multiresolution edge snapper (CAMES) consists of the following two stages: 1)
      automated CA recognition based on a combination of scale-space and statistical
      classification in a multiresolution framework and 2) automated segmentation of
      lumen-intima (LI) and media-adventitia (MA) interfaces for the far (distal) wall
      and IMT measurement. Our database of 365 B-mode longitudinal carotid images is
      taken from four different institutions covering different ethnic backgrounds. The
      ground-truth (GT) database was the average manual segmentation from three
      clinical experts. The mean distance  +/- standard deviation of CAMES with respect
      to GT profiles for LI and MA interfaces were 0.081  +/- 0.099 and 0.082  +/-
      0.197 mm, respectively. The IMT measurement error between CAMES and GT was 0.078 
      +/- 0.112 mm. CAMES was benchmarked against a previously developed automated
      technique based on an integrated approach using feature-based extraction and
      classifier (CALEX). Although CAMES underestimated the IMT value, it had shown a
      strong improvement in segmentation errors against CALEX for LI and MA interfaces
      by 8% and 42%, respectively. The overall IMT measurement bias for CAMES improved
      by 36% against CALEX. Finally, this paper demonstrated that the figure-of-merit
      of CAMES was 95.8% compared with 87.4% for CALEX. The combination of
      multiresolution CA recognition and far-wall segmentation led to an automated, low
      complexity, real-time, and accurate technique for carotid IMT measurement.
      Validation on a multiethnic/multi-institutional data set demonstrated the
      robustness of the technique, which can constitute a clinically valid IMT
      measurement for assistance in atherosclerosis disease management.

PMID- 21947524
TI  - A coding-cost framework for super-resolution motion layer decomposition.
AB  - We consider the problem of decomposing a video sequence into a superposition of
      (a given number of) moving layers. For this problem, we propose an energy
      minimization approach based on the coding cost. Our contributions affect both the
      model (what is minimized) and the algorithmic side (how it is minimized). The
      novelty of the coding-cost model is the inclusion of a refined model of the image
      formation process, known as super resolution. This accounts for camera blur and
      area averaging arising in a physically plausible image formation process. It
      allows us to extract sharp high-resolution layers from the video sequence. The
      algorithmic framework is based on an alternating minimization scheme and includes
      the following innovations. 1) A video labeling, we optimize the layer domains.
      This allows to regularize the shapes of the layers and a very elegant handling of
      occlusions. 2) We present an efficient parallel algorithm for extracting super
      resolved layers based on TV filtering.

PMID- 21947525
TI  - Adaptive Perona-Malik model based on the variable exponent for image denoising.
AB  - This paper introduces a class of adaptive Perona-Malik (PM) diffusion, which
      combines the PM equation with the heat equation. The PM equation provides a
      potential algorithm for image segmentation, noise removal, edge detection, and
      image enhancement. However, the defect of traditional PM model is tending to
      cause the staircase effect and create new features in the processed image.
      Utilizing the edge indicator as a variable exponent, we can adaptively control
      the diffusion mode, which alternates between PM diffusion and Gaussian smoothing
      in accordance with the image feature. Computer experiments indicate that the
      present algorithm is very efficient for edge detection and noise removal.

PMID- 21947526
TI  - The segmentation of the left ventricle of the heart from ultrasound data using
      deep learning architectures and derivative-based search methods.
AB  - We present a new supervised learning model designed for the automatic
      segmentation of the left ventricle (LV) of the heart in ultrasound images. We
      address the following problems inherent to supervised learning models: 1) the
      need of a large set of training images; 2) robustness to imaging conditions not
      present in the training data; and 3) complex search process. The innovations of
      our approach reside in a formulation that decouples the rigid and nonrigid
      detections, deep learning methods that model the appearance of the LV, and
      efficient derivative-based search algorithms. The functionality of our approach
      is evaluated using a data set of diseased cases containing 400 annotated images
      (from 12 sequences) and another data set of normal cases comprising 80 annotated
      images (from two sequences), where both sets present long axis views of the LV.
      Using several error measures to compute the degree of similarity between the
      manual and automatic segmentations, we show that our method not only has high
      sensitivity and specificity but also presents variations with respect to a gold
      standard (computed from the manual annotations of two experts) within interuser
      variability on a subset of the diseased cases. We also compare the segmentations
      produced by our approach and by two state-of-the-art LV segmentation models on
      the data set of normal cases, and the results show that our approach produces
      segmentations that are comparable to these two approaches using only 20 training
      images and increasing the training set to 400 images causes our approach to be
      generally more accurate. Finally, we show that efficient search methods reduce up
      to tenfold the complexity of the method while still producing competitive
      segmentations. In the future, we plan to include a dynamical model to improve the
      performance of the algorithm, to use semisupervised learning methods to reduce
      even more the dependence on rich and large training sets, and to design a shape
      model less dependent on the training set.

PMID- 21947527
TI  - Saliency detection by multitask sparsity pursuit.
AB  - This paper addresses the problem of detecting salient areas within natural
      images. We shall mainly study the problem under unsupervised setting, i.e.,
      saliency detection without learning from labeled images. A solution of multitask
      sparsity pursuit is proposed to integrate multiple types of features for
      detecting saliency collaboratively. Given an image described by multiple
      features, its saliency map is inferred by seeking the consistently sparse
      elements from the joint decompositions of multiple-feature matrices into pairs of
      low-rank and sparse matrices. The inference process is formulated as a
      constrained nuclear norm and as an  l(2, 1)-norm minimization problem, which is
      convex and can be solved efficiently with an augmented Lagrange multiplier
      method. Compared with previous methods, which usually make use of multiple
      features by combining the saliency maps obtained from individual features, the
      proposed method seamlessly integrates multiple features to produce jointly the
      saliency map with a single inference step and thus produces more accurate and
      reliable results. In addition to the unsupervised setting, the proposed method
      can be also generalized to incorporate the top-down priors obtained from
      supervised environment. Extensive experiments well validate its superiority over
      other state-of-the-art methods.

PMID- 21947528
TI  - Web and personal image annotation by mining label correlation with relaxed visual
      graph embedding.
AB  - The number of digital images rapidly increases, and it becomes an important
      challenge to organize these resources effectively. As a way to facilitate image
      categorization and retrieval, automatic image annotation has received much
      research attention. Considering that there are a great number of unlabeled images
      available, it is beneficial to develop an effective mechanism to leverage
      unlabeled images for large-scale image annotation. Meanwhile, a single image is
      usually associated with multiple labels, which are inherently correlated to each
      other. A straightforward method of image annotation is to decompose the problem
      into multiple independent single-label problems, but this ignores the underlying
      correlations among different labels. In this paper, we propose a new inductive
      algorithm for image annotation by integrating label correlation mining and visual
      similarity mining into a joint framework. We first construct a graph model
      according to image visual features. A multilabel classifier is then trained by
      simultaneously uncovering the shared structure common to different labels and the
      visual graph embedded label prediction matrix for image annotation. We show that
      the globally optimal solution of the proposed framework can be obtained by
      performing generalized eigen-decomposition. We apply the proposed framework to
      both web image annotation and personal album labeling using the NUS-WIDE, MSRA MM
      2.0, and Kodak image data sets, and the AUC evaluation metric. Extensive
      experiments on large-scale image databases collected from the web and personal
      album show that the proposed algorithm is capable of utilizing both labeled and
      unlabeled data for image annotation and outperforms other algorithms.

PMID- 21947529
TI  - Reinforcement learning controller design for affine nonlinear discrete-time
      systems using online approximators.
AB  - In this paper, reinforcement learning state- and output-feedback-based adaptive
      critic controller designs are proposed by using the online approximators (OLAs)
      for a general multi-input and multioutput affine unknown nonlinear discretetime
      systems in the presence of bounded disturbances. The proposed controller design
      has two entities, an action network that is designed to produce optimal signal
      and a critic network that evaluates the performance of the action network. The
      critic estimates the cost-to-go function which is tuned online using recursive
      equations derived from heuristic dynamic programming. Here, neural networks (NNs)
      are used both for the action and critic whereas any OLAs, such as radial basis
      functions, splines, fuzzy logic, etc., can be utilized. For the output-feedback
      counterpart, an additional NN is designated as the observer to estimate the
      unavailable system states, and thus, separation principle is not required. The NN
      weight tuning laws for the controller schemes are also derived while ensuring
      uniform ultimate boundedness of the closed-loop system using Lyapunov theory.
      Finally, the effectiveness of the two controllers is tested in simulation on a
      pendulum balancing system and a two-link robotic arm system.

PMID- 21947530
TI  - Brain training: cortical plasticity and afferent feedback in brain-machine
      interface systems.

PMID- 21947531
TI  - 3-d brownian motion simulator for high-sensitivity nanobiotechnological
      applications.
AB  - A wide variety of nanobiotechnologic applications are being developed for
      nanoparticle based in vitro diagnostic and imaging systems. Some of these systems
      make possible highly sensitive detection of molecular biomarkers. Frequently, the
      very low concentration of the biomarkers makes impossible the classical, partial
      differential equation-based mathematical simulation of the motion of the
      nanoparticles involved. We present a three-dimensional Brownian motion simulation
      tool for the prediction of the movement of nanoparticles in various thermal,
      viscosity, and geometric settings in a rectangular cuvette. For nonprofit users
      the server is freely available at the site http://brownian.pitgroup.org.

PMID- 21947532
TI  - Vitamin B12, cognition, and brain MRI measures: a cross-sectional examination.
AB  - OBJECTIVE: To investigate the interrelations of serum vitamin B12 markers with
      brain volumes, cerebral infarcts, and performance in different cognitive domains
      in a biracial population sample cross-sectionally. METHODS: In 121 community
      dwelling participants of the Chicago Health and Aging Project, serum markers of
      vitamin B12 status were related to summary measures of neuropsychological tests
      of 5 cognitive domains and brain MRI measures obtained on average 4.6 years later
      among 121 older adults. RESULTS: Concentrations of all vitamin B12-related
      markers, but not serum vitamin B12 itself, were associated with global cognitive
      function and with total brain volume. Methylmalonate levels were associated with
      poorer episodic memory and perceptual speed, and cystathionine and 2
      methylcitrate with poorer episodic and semantic memory. Homocysteine
      concentrations were associated with decreased total brain volume. The
      homocysteine-global cognition effect was modified and no longer statistically
      significant with adjustment for white matter volume or cerebral infarcts. The
      methylmalonate-global cognition effect was modified and no longer significant
      with adjustment for total brain volume. CONCLUSIONS: Methylmalonate, a specific
      marker of B12 deficiency, may affect cognition by reducing total brain volume
      whereas the effect of homocysteine (nonspecific to vitamin B12 deficiency) on
      cognitive performance may be mediated through increased white matter
      hyperintensity and cerebral infarcts. Vitamin B12 status may affect the brain
      through multiple mechanisms.

PMID- 21947534
TI  - Disparities in NIH funding for epilepsy research.
AB  - Using data from NIH Research Portfolio Online Reporting Tools (RePORT) and
      recently assembled prevalence estimates of 6 major neurologic diseases, we
      compared the relative prevalences and the annual NIH support levels for 6 major
      neurologic disorders: Alzheimer disease, amyotrophic lateral sclerosis (ALS),
      epilepsy, multiple sclerosis, Parkinson disease, and stroke. Compared to these
      other major neurologic disorders, epilepsy research is funded at a persistently
      lower rate based on relative disease prevalences. Relative NIH funding for these
      other disorders in 2010 adjusted for prevalence ranged from 1.7x (stroke) to
      61.1x (ALS) greater than epilepsy. The disparity cannot be explained by
      differences in the overall impact of these diseases on US citizens. Greater
      transparency in the review and funding process is needed to disclose the reason
      for this disparity.

PMID- 21947535
TI  - Rhomboencephalitis due to cocaine-induced bony erosion of skull base.

PMID- 21947536
TI  - Second brain death examination may negatively affect organ donation.

PMID- 21947537
TI  - Teaching NeuroImages: lymphomatoid granulomatosis involving lung and brain in an
      immunocompetent woman.

PMID- 21947538
TI  - Teaching video NeuroImages: cephalic tetanus as a pseudodystonic emergency.

PMID- 21947539
TI  - Responsive neurostimulation for the treatment of seizures that do not respond to
      medication.

PMID- 21947540
TI  - The same ELA class II risk factors confer equine insect bite hypersensitivity in
      two distinct populations.
AB  - Insect bite hypersensitivity (IBH) is a chronic allergic dermatitis common in
      horses. Affected horses mainly react against antigens present in the saliva from
      the biting midges, Culicoides ssp, and occasionally black flies, Simulium ssp.
      Because of this insect dependency, the disease is clearly seasonal and prevalence
      varies between geographical locations. For two distinct horse breeds, we
      genotyped four microsatellite markers positioned within the MHC class II region
      and sequenced the highly polymorphic exons two from DRA and DRB3, respectively.
      Initially, 94 IBH-affected and 93 unaffected Swedish born Icelandic horses were
      tested for genetic association. These horses had previously been genotyped on the
      Illumina Equine SNP50 BeadChip, which made it possible to ensure that our study
      did not suffer from the effects of stratification. The second population
      consisted of 106 unaffected and 80 IBH-affected Exmoor ponies. We show that
      variants in the MHC class II region are associated with disease susceptibility (p
      (raw) = 2.34 * 10(-5)), with the same allele (COR112:274) associated in two
      separate populations. In addition, we combined microsatellite and sequencing data
      in order to investigate the pattern of homozygosity and show that homozygosity
      across the entire MHC class II region is associated with a higher risk of
      developing IBH (p = 0.0013). To our knowledge this is the first time in any
      atopic dermatitis suffering species, including man, where the same risk allele
      has been identified in two distinct populations.

PMID- 21947541
TI  - Toll-like receptor 7 and 8 polymorphisms: associations with functional effects
      and cellular and antibody responses to measles virus and vaccine.
AB  - Successful defence against viral pathogens requires the rapid recognition of
      virus-specific "danger signals" and the activation of both innate and adaptive
      immunity. Toll-like receptors (TLR) 7 and 8 play a critical role in the
      elimination of viruses by recognising the common viral component, single stranded
      (ss)RNA. Measles virus, an ssRNA virus, continues to cause serious morbidity and
      mortality worldwide despite available measles vaccines. TLR7 and TLR8 genetic
      variation may cause functional alterations that result in impaired responses to
      measles. In a population of 12-month-old Australian infants, receptor protein
      expression was examined to assess the functionality of TLR7 and TLR8
      polymorphisms, and the effects of these polymorphisms on cellular and antibody
      responses after the first measles vaccine dose were investigated. TLR7 Leu11Gln
      showed associations with TNF-alpha responses after ligand (imiquimod) stimulation
      in males only (P = 0.040), and non-responders were more likely to be Gln males (P
      = 0.044). TNF-alpha non-responders after imiquimod also had higher percentages of
      TLR8 -4284TT (69.6%) (P = 0.001) and TLR8 -558CC (69.6%) (P = 0.002) in females.
      Receptor protein expression after imiquimod or measles stimulation was not
      significantly altered compared with baseline, nor was it affected by genotype.
      None of the TLR7 or TLR8 polymorphisms studied were associated with measles
      specific cytokine levels or with measles IgG levels. In conclusion, we report
      gender-specific associations with TLR7 and TLR8 polymorphisms and TNF-alpha
      cellular responses to its ligand. However, we found no evidence of any functional
      effects of TLR7 or TLR8 polymorphisms on receptor expression, measles-specific
      cellular responses or measles vaccine antibody responses.

PMID- 21947542
TI  - Signatures of historical demography and pathogen richness on MHC class I genes.
AB  - The extreme polymorphism of MHC class I has been argued to be driven by balancing
      selection from pathogens, with the prediction that populations exposed to a wider
      variety of diseases should have higher diversity. We assembled a global database
      of allotype frequencies for MHC class I genes and investigated possible drivers
      of genetic diversity, measured in different ways. We first looked for a decline
      in diversity with distance from Africa (a consequence of drift during human
      expansions) and then investigated the link with pathogen richness once the effect
      of drift had been corrected for. Using heterozygosity, we recovered a clear
      decline in diversity from Africa and confirmed the positive relationship between
      genetic diversity and pathogen richness for all three classical MHC class I
      genes. However, when we considered a sequence-based measure of genetic diversity,
      the correlation with geographic distance from Africa vanished for HLA-C, and the
      correlations with pathogen richness for the three MHC class I genes were much
      weaker. HLA-C is known to consist of two functional classes of allotypes
      (classified with respect to the 80th residue), which interact with different KIR
      receptors. While this separation provided some improvement in the fit between
      genetic diversity and distance from Africa for one class, much clearer and
      consistent patterns were recovered when we used the 90th residue to separate HLA
      C allotypes into two new classes. This suggests that this residue, which is also
      involved in the binding of KIR, might have had an important evolutionary role
      that has been overlooked.

PMID- 21947543
TI  - The effect of N-nitrosodimethylamine (NDMA) on Bax and Mcl-1 expression in human
      neutrophils.
AB  - In the present study we examined a role of pro-apoptotic Bax and anti-apoptotic
      Mcl-1 proteins, participating in the regulation of intrinsic apoptosis pathway in
      human neutrophils (PMNs) exposed to N-nitrosodimethylamine (NDMA), the
      environmental xenobiotic. For the purpose comparison, the same studies were
      conducted in autologous peripheral blood mononuclear cells (PBMCs). The
      production of cytochrome c by PMNs was also determined. A deficit of anti
      apoptotic Mcl-1 and overexpression of the pro-apoptotic protein Bax suggest that
      the apoptosis process in human neutrophils exposed to NDMA is dependent on
      changes in the expression of these proteins. PMNs were more sensitive to NDMA
      than PBMCs.

PMID- 21947544
TI  - Relationship between gonad maturation and heavy metal accumulation in the clam,
      Galatea paradoxa (Born 1778) from the Volta estuary, Ghana.
AB  - The relationship between gonadal development and the concentrations of four heavy
      metals Mn, Zn, Fe and Hg in the tissues of the clam Galatea paradoxa was
      evaluated at the Volta estuary, Ghana, over an 18-month period. Metal
      concentrations in the clam tissues were highly variable over the sampling period
      and seemed to be influenced by the reproductive cycle of the clam. Mn
      concentrations varied over a wide range from 49 to 867 MUg/g and exhibited a
      significant positive correlation with gonadal development (p = 0.0146, r(2) =
      0.3190). Zn and Fe concentrations ranged from 13 to 59 MUg/g and 79 to 484 MUg/g,
      respectively and both revealed negative relationships between gonad development
      and metal accumulation (Zn (p = 0.0554, r(2) = 0.0554) and Fe (p = 0.1040, r(2) =
      0.1567)). Hg concentrations ranged from 0.026 to 0.059 MUg/g over the sampling
      period and exhibited a slight positive relationship between gonadal development
      and metal accumulation (p = 0.0861, r(2) = 0.1730).

PMID- 21947545
TI  - Sinus augmentation with phycogene hydroxyapatite: histological and
      histomorphometrical results after 6 months in humans. A case series.
AB  - BACKGROUND: Phycogene hydroxyapatite is a biological hydroxyapatite derived from
      calcifying maritime algae, and is prepared by hydrothermal conversion by
      pyrolitical segmentation of the calcium carbonate of native algae into
      fluorhydroxyapatite. The aim of the present study was a histological and
      histomorphometrical evaluation, in humans, of specimens retrieved from sinuses
      augmented with phycogene hydroxyapatite, after a healing period of 6 months. CASE
      SERIES: Ten healthy patients with noncontributory past medical history (four
      women and six men, all nonsmokers, mean age 59 years, range 54-65 years) were
      included in this study. All patients were candidates for augmentation in the
      posterior maxilla in order to receive fixed restorations. The maxillary sinuses
      were filled with phycogene hydroxyapatite (Algipore(r), Dentsply Friadent,
      Mannheim, Germany). Twenty-three implants (XiVE(r), Dentsply Friadent, Mannheim,
      Germany) were placed in the augmented sinuses after a healing period of about 6
      months. The bone cores were retrieved and were processed for histology. Most
      particles of phycogene hydroxyapatite were surrounded by a mineralized tissue,
      and the biomaterial particles had served as an osteoconductive scaffold. Most
      particles were bridged by newly formed bone characterized by the presence of
      large osteocytic lacunae, also around the phycogene hydroxyapatite particles,
      which appeared to be partially resorbed and substituted by new bone. No
      inflammatory cells or foreign body reaction cells were present around the
      biomaterial. No gaps were present at the bone-particle interface, and the bone
      was always in close contact with the particles. Histomorphometry showed that the
      percentage of newly formed bone was 35.2 +/- 3.6%, marrow spaces 35.6 +/- 2.3%,
      and residual grafted material 37.1 +/- 3.8%. DISCUSSION: In conclusion, the
      present results support the literature findings that phycogene hydroxyapatite can
      be used, successfully, for sinus augmentation procedures.

PMID- 21947546
TI  - Inhibition of Lassa virus and Ebola virus infection in host cells treated with
      the kinase inhibitors genistein and tyrphostin.
AB  - Arenaviruses and filoviruses are capable of causing hemorrhagic fever syndrome in
      humans. Limited therapeutic and/or prophylactic options are available for humans
      suffering from viral hemorrhagic fever. In this report, we demonstrate that pre
      treatment of host cells with the kinase inhibitors genistein and tyrphostin
      AG1478 leads to inhibition of infection or transduction in cells infected with
      Ebola virus, Marburg virus, and Lassa virus. In all, the results demonstrate that
      a kinase inhibitor cocktail consisting of genistein and tyrphostin AG1478 is a
      broad-spectrum antiviral that may be used as a therapeutic or prophylactic
      against arenavirus and filovirus hemorrhagic fever.

PMID- 21947547
TI  - Population dynamics of red-backed voles (Myodes) in North America.
AB  - We review the population dynamics of red-backed voles (Myodes species) in North
      America, the main deciduous and coniferous forest-dwelling microtines on this
      continent, and compare and contrast their pattern with that of the same or
      similar species in Eurasia. We identify 7 long-term studies of population changes
      in Myodes in North America. Using autoregressive and spectral analysis, we found
      that only 2 of the 7 show 3- to 5-year cycles like those found in some Eurasian
      populations. There was no relationship between latitude and cycling. The general
      lack of cyclicity is associated with two key aspects of their demography that act
      in tandem: first, poor overwinter survival in most years; second, chronically low
      densities, with irregular outbreak years. Eight factors might explain why some
      Myodes populations fluctuate in cycles and others fluctuate irregularly, and we
      review the evidence for each factor: food supplies, nutrients, predation,
      interspecific competition, disease, weather, spacing behavior and interactive
      effects. Of these eight, only food supplies appear to be sufficient to explain
      the differences between cyclic and non-cyclic populations. Irregular fluctuations
      are the result of pulsed food supplies in the form of berry crops (M. rutilus) or
      tree seeds (M. gapperi) linked to weather patterns. We argue that, to understand
      the cause for the patterns in the respective hemispheres, we must know the
      mechanism(s) driving population change and this must be linked to rigorous field
      tests. We suggest that a large-scale, year-round feeding experiment should
      improve overwintering survival, increase standing densities, and flip non-cyclic
      Myodes populations into cyclic dynamics that would mimic the patterns seen in the
      cyclic populations found in parts of Eurasia.

PMID- 21947548
TI  - Predator-prey relationships in a Mediterranean vertebrate system: Bonelli's
      eagles, rabbits and partridges.
AB  - How predators impact on prey population dynamics is still an unsolved issue for
      most wild predator-prey communities. When considering vertebrates, important
      concerns constrain a comprehensive understanding of the functioning of predator
      prey relationships worldwide; e.g. studies simultaneously quantifying
      'functional' and 'numerical responses' (i.e., the 'total response') are rare. The
      functional, the numerical, and the resulting total response (i.e., how the
      predator per capita intake, the population of predators and the total of prey
      eaten by the total predators vary with prey densities) are fundamental as they
      reveal the predator's ability to regulate prey population dynamics. Here, we used
      a multi-spatio-temporal scale approach to simultaneously explore the functional
      and numerical responses of a territorial predator (Bonelli's eagle Hieraaetus
      fasciatus) to its two main prey species (the rabbit Oryctolagus cuniculus and the
      red-legged partridge Alectoris rufa) during the breeding period in a
      Mediterranean system of south Spain. Bonelli's eagle responded functionally, but
      not numerically, to rabbit/partridge density changes. Type II, non-regulatory,
      functional responses (typical of specialist predators) offered the best fitting
      models for both prey. In the absence of a numerical response, Bonelli's eagle
      role as a regulating factor of rabbit and partridge populations seems to be weak
      in our study area. Simple (prey density-dependent) functional response models may
      well describe the short-term variation in a territorial predator's consumption
      rate in complex ecosystems.

PMID- 21947550
TI  - Design and development of microbioreactors for long-term cell culture in
      controlled oxygen microenvironments.
AB  - The ability to control the oxygen level to which cells are exposed in tissue
      culture experiments is crucial for many applications. Here, we design, develop
      and test a microbioreactor (MBR) for long-term cell culture studies with the
      capability to accurately control and continuously monitor the dissolved oxygen
      (DO) level in the cell microenvironment. In addition, the DO level can be
      controlled independently from other cues, such as the viscous shear-stress acting
      on the cells. We first analyze the transport of oxygen in the proposed device and
      determine the materials and dimensions that are compatible with uniform oxygen
      tension and low shear-stress at the cell level. The device is also designed to
      culture a statistically significant number of cells. We use fully transparent
      materials and the overall design of the device is compatible with live-cell
      imaging. The proposed system includes real-time read-out of actual DO levels, is
      simple to fabricate at low cost, and can be easily expanded to control the
      concentration of other microenvironmental solutes. We performed control
      experiments in the absence of cells to demonstrate that the MBR can be used to
      accurately modulate DO levels ranging from atmospheric level to 1%, both under no
      flow and perfusion conditions. We also demonstrate cancer cell attachment and
      viability within the MBR. The proposed MBR offers the unprecedented capability to
      perform on-line measurement and analysis of DO levels in the microenvironment of
      adherent cultures and to correlate them with various cellular responses.

PMID- 21947549
TI  - Prevalence, awareness, treatment, control and risk factors for hypertension in a
      rural population in South India.
AB  - OBJECTIVES: Hypertension is a major public health problem with prevalence ranging
      22-30% in urban India. There are few data on hypertension epidemiology in rural
      India. We conducted a survey to estimate prevalence, awareness, treatment,
      control and risk factors for hypertension in a rural population in south India.
      METHODS: We did cross-sectional survey in 11 villages in Tamil Nadu. We collected
      data on behavioral risk factors, anthropometric and blood pressure measurements.
      We defined hypertension according to WHO criteria. RESULTS: Study population
      included 10,463 subjects aged 25-64 years. Among them, 4,900 (46.8%) were males.
      Hypertension was present for 2,247 (21.4%) subjects and 1,682 (74.9%) among
      hypertensives were newly detected. Overall 20% were on treatment and 6.6% had
      blood pressure control. Age >=35 years, BMI >= 23 kg/m(2) and central obesity
      were risk factors significantly associated with hypertension (p < 0.05). In
      addition, alcohol consumption, higher education level were risk factor among
      males and family history of hypertension was risk factor among females (p <
      0.05). CONCLUSION: Hypertension is an emerging challenge in rural India. We need
      health promotion programs and reorientation of primary health care to improve
      hypertension detection and management.

PMID- 21947551
TI  - GSTP1 CpG island hypermethylation for DNA-based detection of occult tumor cells
      in surgical margins after radical prostatectomy.
AB  - OBJECTIVE: The risk of local recurrence after radical prostatectomy (RP) is
      considerably dependent on local tumor stage. To improve local staging, the aim of
      this study was to assess the feasibility of quantitative methylation-specific PCR
      (Q-MSP) for the identification of promoter hypermethylation of the detoxifying
      glutathione-S-transferase P1 gene (GSTP1) to detect occult prostate cancer (PCa)
      cells in the prostatic fossa after RP. METHODS: A total of 39 consecutive
      patients with clinically organ-confined PCa underwent RP. After gland excision,
      biopsies were obtained from eight defined areas of the prostatic fossa and
      bisected for both histopathological and molecular analyses. Results were related
      to clinicopathological data including tumor stage, Gleason score, prostate
      specific antigen (PSA), and biochemical recurrence. RESULTS: Of 39 patients, 11
      with PCa had at least one positive molecular margin status indicated by GSTP1
      methylation. These included 5 of 17 (29.4%) with organ-confined and 6 of 22
      (27.3%) with advanced (>=pT3 and/or pN+) PCa. GSTP1 methylation in surgical
      margins strongly correlated with histopathological R-status (P = 0.022) and
      preoperative PSA (P = 0.01) whereas no association with tumor stage (pT2 vs pT3),
      grade (Gleason score <7 vs >=7), and lymph node status was found. No patient
      experienced biochemical relapse. CONCLUSIONS: GSTP1 hypermethylation detected by
      Q-MSP in prostatic fossa biopsies after RP is well suited for the detection of
      occult tumor cells in surgical margins. However, the limited number of patients
      and the short-term follow-up does not allow definite conclusions on the
      prognostic value of GSTP1 in surgical margins.

PMID- 21947552
TI  - Entrapment of the StarClose Vascular Closure System after attempted common
      femoral artery deployment.
AB  - A complication of the StarClose Vascular Closure System (Abbott, Des Plaines, IL)
      after a transarterial hepatic chemoembolization is described. After attempted
      clip deployment, the entire device became lodged in the tissues overlying the
      common femoral artery and could not be removed percutaneously. Successful removal
      of the device required surgical cutdown for removal and arterial repair.
      Entrapment of the StarClose vascular closure deployment system is a potentially
      serious complication that has been reported in the Manufacturer and User Facility
      Device Experience database, but has not been recognized in the literature.

PMID- 21947553
TI  - Complete recovery after surgical resection of left Wernicke's area in awake
      patient: a brain stimulation and functional MRI study.

PMID- 21947554
TI  - A management algorithm for cerebrospinal fluid leak associated with anterior
      skull base fractures: detailed clinical and radiological follow-up.
AB  - Detailed outcome data for the management of anterior skull base fractures
      associated with cerebrospinal fluid (CSF) leakage is lacking. We present detailed
      follow-up data of a single-center study using a predetermined algorithm for the
      management of CSF leakage secondary to traumatic fractures. A number of 138
      consecutive patients were included in the analysis; all patients underwent high
      resolution computed tomography (CT) scanning at time of admission with beta(2)
      transferrin testing used to confirm CSF leakage. Patients with acute surgical
      indications were operated as emergent; leaks were repaired at the time of initial
      surgery in patients with intracranial pressure < 15 cm H(2)O. The remainder of
      the study population was managed conservatively including use of prophylactic
      antibiotics; lumbar drainage (LD) catheters were placed in those patients with
      leakage persisting beyond 48 h. Leaks lasting longer than 5 days underwent
      microsurgical repair using an intradural bicoronal approach. One-year follow-up
      assessment included evaluation of neurological status, Glasgow Outcome Scale
      (GOS), and repeat head CT. Twenty eight patients (26.9%) underwent emergent
      surgery, 15 of whom had simultaneous CSF leak repair, whereas 76 patients (73.1%)
      underwent delayed CSF leak repair between days 5 and 14. Postoperative meningitis
      rate was low (1.9%). Postoperative CSF leak (1.9%) was managed by intradural or
      transnasal endoscopic operation. Comparable rates of anosmia and frontal lobe
      hypodensities were seen in the surgical and conservatively managed subgroups. The
      presented algorithm, utilizing prophylactic antibiotics, trial of LD, acute
      and/or delayed intradural microsurgery, yields favorable outcomes. Large
      randomized controlled trials are needed to better define the role of prophylactic
      antibiotics and to better characterize the optimal timing and approach of
      surgical repair.

PMID- 21947556
TI  - Rapid functional evaluation of beta-cells by extracellular recording of membrane
      potential oscillations with microelectrode arrays.
AB  - The membrane potential (V (m)) of beta-cells oscillates at glucose concentrations
      between ~6 and 25 mM, i.e. burst phases with action potentials alternate with
      silent interburst phases generating so-called slow waves. The slow waves drive
      oscillations of the cytosolic Ca(2+) concentration ([Ca(2+)](c)) and insulin
      secretion. The length of the bursts correlates with the amount of insulin
      release. Thus, the fraction of plateau phase (FOPP), i.e. the percentage of time
      with burst activity, is an excellent marker for beta-cell function and metabolic
      integrity. Extracellular voltage changes of mouse islets were measured using a
      microelectrode array (MEA) allowing the detection of burst and interburst phases.
      At a non-stimulating glucose concentration (3 mM) no electrical activity was
      detectable while bursting was continuous at 30 mM. The glucose concentration
      response (determined as FOPP) curve revealed half-maximal stimulation at 12 +/- 1
      mM (Hill equation fit). The signal was sensitive to K(ATP) channel modulators,
      e.g. tolbutamide or diazoxide. Simultaneous recordings of electrical activity and
      [Ca(2+)](c) revealed congruent bursts and peaks, respectively. The extracellular
      recordings are in perfect agreement with more time-consuming intracellular
      electrical recordings. The results provide a 'proof-of-principle' for detection
      of beta-cell slow waves and determination of the FOPP using extracellular
      electrodes in a MEA-based system. The method is facile and provides the
      capability to study the effects of modulators of beta-cell function including
      possible anti-diabetic drugs in real time. Moreover, the method may be useful for
      checking the metabolic integrity of human donor islets prior to transplantation.

PMID- 21947555
TI  - How mental stress affects endothelial function.
AB  - Mental stress is an important factor contributing to recognized mechanisms
      underlying cardiovascular events. Among these, stress-related endothelial
      dysfunction is an early risk factor that predicts future development of severe
      cardiovascular disorders. Acute mental stress by a variety of tests impairs
      endothelial function in humans, although the opposite results have been reported
      by some investigators. Chronic stress always deteriorates endothelial function in
      humans and experimental animals. Stress hormones, such as glucocorticoids and pro
      inflammatory cytokines, and endothelin-1 liberated in response to mental stress
      participate in endothelial dysfunction possibly via downregulation of endothelial
      nitric oxide synthase (eNOS) expression, eNOS inactivation, decreased nitric
      oxide (NO) actions, and increased NO degradation, together with vasoconstriction
      counteracting against NO-induced vasodilatation. Catecholamines do not directly
      affect endothelial function but impair its function when blood pressure elevation
      by the amines is sustained. Endogenous opioids favorably affect endothelial
      function, which counteract deteriorating effects of other stress hormones and
      mediators. Inhibition of cortisol and endothelin-1 production, prevention of pro
      inflammatory mediator accumulation, hypnotics, mirthful laughter, humor
      orientation, and lifestyle modification would contribute to the prevention and
      treatment for stress-related endothelial dysfunction and future serious
      cardiovascular disease.

PMID- 21947557
TI  - A systematic review on the contributions of edible plant and animal biodiversity
      to human diets.
AB  - The sustainable use of natural and agricultural biodiversity in the diet can be
      instrumental to preserve existing food biodiversity, address malnutrition, and
      mitigate adverse effects of dietary changes worldwide. This systematic review of
      literature summarizes the current evidence on the contribution of plant and
      animal biodiversity to human diets in terms of energy intake, micronutrient
      intake, and dietary diversification. Peer-reviewed studies were searched in ten
      databases using pre-defined search terms. Only original studies assessing food
      biodiversity and dietary intake were included, resulting in a total of 34
      studies. 7, 14, and 17 studies reported information in relation to energy intake,
      micronutrient intake, and dietary diversification, respectively. In general,
      locally available foods were found to be important sources of energy,
      micronutrients, and dietary diversification in the diet of particularly rural and
      forest communities of highly biodiverse ecosystems. The current evidence shows
      local food biodiversity as important contributor of nutritious diets. Findings
      are, however, limited to populations living in highly biodiverse areas. Research
      on the contribution of biodiversity in diets of industrialized and urban settings
      needs more attention. Instruments are needed that would more appropriately
      measure the dietary contribution of local biodiversity.

PMID- 21947558
TI  - Thyrotropin-releasing hormone as a treatment for cancer-related fatigue: a
      randomized controlled study.
AB  - BACKGROUND: Fatigue is a common and often disabling symptom for cancer patients.
      To date, no pharmacological interventions have shown reliable efficacy in
      treatment of cancer-related fatigue (CF). Thyrotropin-releasing hormone (TRH), a
      key regulator of homeostasis, exerts arousing and analeptic actions in instances
      of behavioral depression. In the present pilot, randomized, placebo-controlled,
      crossover study, we investigated the efficacy and safety of TRH as a treatment
      for CF. METHODS: Patients with cancer experiencing significant fatigue without
      medically reversible causes were enrolled in this study. The primary outcome
      measure was the visual analog scale for energy (VAS-E) assessed at 3, 7, and 24 h
      post-study medication administration. Secondary outcome measures included the
      profile of mood states (POMS) questionnaire, a 6-min walking test, the hospital
      anxiety and depression scale, the Leeds sleep questionnaire, and assessment of
      quality of life using the Functional Assessment of Chronic Illness Therapy
      Fatigue (FACIT-F). RESULTS: Eight patients completed the study. TRH
      administration was associated with significant improvement in fatigue level as
      measured by the VAS-E, the fatigue and vigor subscales of the POMS, and the
      fatigue subscale of FACIT-F (p < 0.05). It was also associated with a positive
      impact on quality of life. TRH administration was associated with transient
      increases in blood pressure and heart rate. CONCLUSIONS: TRH administration was
      efficacious, safe, and tolerable in the treatment of CF with a positive impact on
      quality of life. These results provide a crucial impetus for pursuing TRH
      therapeutics to treat CF.

PMID- 21947559
TI  - Certain bio-psychosocial-spiritual problems associated with dyspnea among
      advanced cancer patients in Taiwan.
AB  - PURPOSE: Dyspnea is a multidimensional phenomenon among advanced cancer patients.
      We aim to explore the association between bio-psychosocial-spiritual problems and
      dyspnea among advanced cancer patients in Taiwan. METHODS: We retrospectively
      analyzed advanced cancer patients admitted to the hospice palliative ward in a
      tertiary hospital in Taiwan from 2002 to 2005. A total of 687 consecutive
      advanced cancer patients were enrolled. Physical, psychosocial, and spiritual
      problems for each patient were collected. Multiple logistic regression analyses
      were used to evaluate the association between dyspnea and other physical,
      psychosocial, and spiritual problems. RESULTS: The top four primary sites of
      cancer among these patients are the liver/biliary tract (19.9%), lung (15.6%),
      colon/rectum (12.8%), and head/neck (9.9%). During admission period, 260 (37.8%)
      patients experienced dyspnea. For primary cancer types and metastatic locations,
      subjects with dyspnea tended to have lung cancer, lung metastasis, or brain
      metastasis. The clinical symptoms/signs related to dyspnea are pain, anorexia,
      constipation, nausea/vomiting, coughing, pleural effusion, edema, anxiety, and
      propriety preparation problem, that is, arranging one's will, feelings of
      isolation, fear of death, and survival. After further adjustments for potential
      confounders, subjects with problems of propriety preparation were found to be
      strongly associated with dyspnea. The adjusted odds ratio of having dyspnea
      caused by the problem of propriety preparation was 1.91 (95% confidence interval,
      1.15-3.19). CONCLUSIONS: Advanced cancer patients with certain psychosocial and
      spiritual problems, such as, the problem of propriety preparation, fear of death,
      and anxiety, tended to have dyspnea. Among these factors, propriety preparation
      plays an important role among dyspnea patients. Advanced cancer patients with
      dyspnea have greater needs for propriety preparation.

PMID- 21947560
TI  - Assessing cancer patients' trust in their oncologist: development and validation
      of the Trust in Oncologist Scale (TiOS).
AB  - PURPOSE: The aim of this study was to develop and validate the Trust in
      Oncologist Scale (TiOS), which aims to measure cancer patients' trust in their
      oncologist. Structure, reliability and validity were examined. METHODS:
      Construction of the TiOS was based on a multidimensional theoretical framework.
      Cancer patients were surveyed within a week after their consultation. Trust,
      satisfaction, trust in health care, self-reported health and background variables
      were assessed. Dimensionality, internal consistency, test-retest reliability and
      construct validity were investigated. RESULTS: Data of 423 patients were included
      (response rate = 65%). After item reduction, the TiOS included 18 items. Trust
      scores were high. Exploratory factor analysis suggested one-dimensionality.
      Confirmatory factor analysis nevertheless indicated a reasonable fit of our four
      dimensional theoretical model, distinguishing competence, fidelity, honesty and
      caring. Internal consistency and test-retest reliabilities were high. Good
      construct validity was indicated by moderate correlations of trust (TiOS) with
      satisfaction, trust in health care, willingness to recommend and number of
      consultations with the oncologist. Exploratory analyses suggested significant
      correlations of trust with ethnicity and age. CONCLUSIONS: The TiOS reliably and
      validly assesses cancer patients' trust in their oncologist. The questionnaire
      can be employed in both clinical practice and future research of cancer patients'
      trust.

PMID- 21947561
TI  - An extended 15 Hz ERG protocol (1): the contributions of primary and secondary
      rod pathways and the cone pathway.
AB  - The minimum in the amplitude versus flash strength curve of dark-adapted 15 Hz
      electroretinograms (ERGs) has been attributed to interactions between the primary
      and secondary rod pathways. The 15 Hz ERGs can be used to examine the two rod
      pathways in patients. However, previous studies suggested that the cone-driven
      pathway also contributes to the 15 Hz ERGs for flash strengths just above that of
      the minimum. We investigated cone pathway contributions to improve upon the
      interpretation of (abnormal) 15 Hz ERGs measured in patients. We recorded 15 Hz
      ERGs in five healthy volunteers, using a range of flash strengths that we
      extended to high values. The stimuli were varied in both colour (blue, green,
      amber, and red) and flash duration (short flash and square wave) in order to
      stimulate rods and cones in various ways. The differences in the responses to the
      four colours could be fully explained by the spectral sensitivity of rods for
      flash strengths up to approximately 12.5 log quanta.deg(-2). At higher flash
      strengths, higher-order harmonics appeared in the responses which could be
      attributed to cones being more sensitive than rods to higher frequencies.
      Furthermore, the amplitude curves of the blue and green responses showed a second
      minimum suggesting rod to cone interactions. We present a descriptive model of
      the contributions of the rod and cone pathways. In clinical application, we would
      advise using the short flash flicker instead of the square wave flicker, as the
      responses are of larger amplitude, and cone pathway contributions can be
      recognized from large higher-order harmonics.

PMID- 21947562
TI  - Risks and benefits of consumption of Great Lakes fish.
AB  - BACKGROUND: Beneficial effects of fish consumption on early cognitive development
      and cardiovascular health have been attributed to the omega-3 fatty acids in fish
      and fish oils, but toxic chemicals in fish may adversely affect these health
      outcomes. Risk-benefit assessments of fish consumption have frequently focused on
      methylmercury and omega-3 fatty acids, not persistent pollutants such as
      polychlorinated biphenyls, and none have evaluated Great Lakes fish consumption.
      OBJECTIVES: The risks and benefits of fish consumption have been established
      primarily for marine fish. Here, we examine whether sufficient data are available
      to evaluate the risks and benefits of eating freshwater fish from the Great
      Lakes. METHODS: We used a scoping review to integrate information from multiple
      state, provincial, and federal agency sources regarding the contaminants and
      omega-3 fatty acids in Great Lakes fish and fish consumers, consumption rates and
      fish consumption advisories, and health effects of contaminants and omega-3 fatty
      acids. DATA SYNTHESIS: Great Lakes fish contain persistent contaminants--many of
      which have documented adverse health effects--that accumulate in humans consuming
      them. In contrast, data are sparse on omega-3 fatty acids in the fish and their
      consumers. Moreover, few studies have documented the social and cultural benefits
      of Great Lakes fish consumption, particularly for subsistence fishers and native
      communities. At this time, federal and state/provincial governments provide fish
      consumption advisories based solely on risk. CONCLUSIONS: Our knowledge of Great
      Lakes fish has critical gaps, particularly regarding the benefits of consumption.
      A risk-benefit analysis requires more information than is currently available on
      the concentration of omega-3 fatty acids in Great Lakes fish and their absorption
      by fish eaters in addition to more information on the social, cultural, and
      health consequences of changes in the amount of fish consumed.

PMID- 21947565
TI  - Identification of lineage III of G12 rotavirus strains in diarrheic children in
      the Northern Region of Brazil between 2008 and 2010.
AB  - This study reports on the surveillance for rotavirus genotypes and the
      identification of G12 human rotavirus in the Northern Region of Brazil. Rotavirus
      positive samples were collected from children <5 years of age with acute diarrhea
      from January 2008 to October 2010. G2P[4] was the most prevalent genotype,
      accounting for 45.6% (126/303) of cases. Five rotavirus strains bearing G12P[6]
      genotype specificity were detected. Phylogenetic analysis of the VP7 gene showed
      that G12 strains clustered into lineage III. This is the first detection of G12
      strains from lineage III in Latin America, broadening the current evidence for
      the worldwide emergence of this genotype.

PMID- 21947564
TI  - Breast cancer risk in atomic bomb survivors from multi-model inference with
      incidence data 1958-1998.
AB  - Breast cancer risk from radiation exposure has been analyzed in the cohort of
      Japanese a-bomb survivors using empirical models and mechanistic two-step clonal
      expansion (TSCE) models with incidence data from 1958 to 1998. TSCE models rely
      on a phenomenological representation of cell transition processes on the path to
      cancer. They describe the data as good as empirical models and this fact has been
      exploited for risk assessment. Adequate models of both types have been selected
      with a statistical protocol based on parsimonious parameter deployment and their
      risk estimates have been combined using multi-model inference techniques. TSCE
      models relate the radiation risk to cell processes which are controlled by age
      increasing rates of initiating mutations and by changes in hormone levels due to
      menopause. For exposure at young age, they predict an enhanced excess relative
      risk (ERR) whereas the preferred empirical model shows no dependence on age at
      exposure. At attained age 70, the multi-model median of the ERR at 1 Gy decreases
      moderately from 1.2 Gy(-1) (90% CI 0.72; 2.1) for exposure at age 25 to a 30%
      lower value for exposure at age 55. For cohort strata with few cases, where model
      predictions diverge, uncertainty intervals from multi-model inference are
      enhanced by up to a factor of 1.6 compared to the preferred empirical model.
      Multi-model inference provides a joint risk estimate from several plausible
      models rather than relying on a single model of choice. It produces more reliable
      point estimates and improves the characterization of uncertainties. The method is
      recommended for risk assessment in practical radiation protection.

PMID- 21947566
TI  - Porcine reproductive and respiratory syndrome virus nucleocapsid protein
      modulates interferon-beta production by inhibiting IRF3 activation in
      immortalized porcine alveolar macrophages.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) infection appears to
      elicit a weak innate immune response suppressing type 1 interferon (IFN)
      production. Recent studies have revealed that several nonstructural proteins
      encoded by the PRRSV genome independently antagonize the type 1 IFN system. The
      present study sought to identify the structural proteins that possess the immune
      evasion properties in immortalized porcine alveolar macrophages (PAM). Each
      structural protein gene was stably expressed in a porcine monocyte-derived
      macrophage cell line, PAM-pCD163, and tested for its potential to inhibit IFN
      beta induction. We then focused on the nucleocapsid (N) protein, which has a
      strong inhibitory effect on dsRNA-induced IFN-beta production. Upon dsRNA
      stimulation, IFN-beta production was shown to decrease proportionally with
      increasing levels of N expression. Furthermore, the PRRSV N protein was found to
      down-regulate IFN-dependent gene production by dsRNA. Taken together, these
      results indicate the ability of N to modulate the dsRNA-mediated IFN induction
      pathways. In addition, the N protein significantly interfered with dsRNA-induced
      phosphorylation and nuclear translocation of IRF3. Our data suggest that the
      PRRSV N protein is a responsible component, independent of other nonstructural
      elements, for evading the IFN response by antagonizing IRF3 activation.

PMID- 21947567
TI  - Regulation of gene expression by the NSP1 and NSP3 non-structural proteins of
      rotavirus.
AB  - The role of the rotavirus non-structural proteins NSP1 and NSP3 in regulating
      cellular and viral mRNA translation has been investigated by examining the effect
      of added recombinant NSP3 on protein translation in a T7-based in vitro coupled
      transcription-translation system. Addition of purified NSP3 to assays primed
      solely with cellular mRNA was found to have no effect on the translation
      efficiency of the mRNA. However, as expected, the addition of viral mRNA to such
      assays competitively inhibited the synthesis of cellular protein, and
      interestingly, this inhibition was enhanced by the addition of NSP3. Treatment of
      NSP3 with antisera raised against the purified protein abrogated its function,
      but only when used prior to mixing the protein with viral mRNA. Addition of
      partially purified NSP1 to the coupled system was able to alleviate the
      enhancement of the inhibition of cellular mRNA translation caused by NSP3. The
      role of NSP1 in this process appears to be to modulate the impact of the NSP3
      based inhibition of cellular translation by binding to the 5' end of viral mRNAs.

PMID- 21947568
TI  - Rescue of avian adeno-associated virus from a recombinant plasmid containing
      deletions in the viral inverted terminal repeats.
AB  - We have previously reported the complete genome sequence of avian adeno
      associated virus (AAAV) strain YZ-1, isolated from healthy chickens in China. In
      this study, we describe the successful rescue of infectious virions from a
      recombinant plasmid containing the genome of YZ-1 with deletions in the viral
      inverted terminal repeats (ITRs). The complete genome of YZ-1 was cloned into a
      bacterial plasmid by a modified "A-T" cloning method. Six recombinant plasmids
      were selected for further experiments. Sequence analysis indicated that the six
      clones shared identical internal sequences except for the various deletions
      within ITRs at either end of the cloned genome. The recombinant plasmid pYZ525,
      harboring a YZ-1 genome with a 96-nt deletion at the 5' end, was used to
      transfect CEL or HEK293 cells in the presence of the CELO virus or a helper
      plasmid, and rescued virions were obtained by both of the methods despite the
      presence of the deletions. Here, for the first time, we provide evidence that a
      certain number of nt deletions in the ITRs are not lethal for the rescue of
      viable AAAV from recombinant plasmids. This study provides insight into the
      unique biology of AAAV and the mechanism of viral replication.

PMID- 21947569
TI  - Conformational transitions of the catalytic domain of heme-regulated eukaryotic
      initiation factor 2alpha kinase, a key translational regulatory molecule.
AB  - In mammalian cells, the heme-regulated inhibitor (HRI) plays a critical role in
      the regulation of protein synthesis at the initiation step through
      phosphorylation of alpha-subunit of the eukaryotic initiation factor 2 (eIF2). In
      this study we have cloned and performed biophysical characterization of the
      kinase catalytic domain (KD) of rabbit HRI. The KD described here comprises
      kinase 1, the kinase insertion domain (KI) and kinase 2. We report here the
      existence of an active and stable monomer of HRI (KD). The HRI (KD) containing
      three tryptophan residues was examined for its conformational transitions
      occurring under various denaturing conditions using steady-state and time
      resolved tryptophan fluorescence, circular dichroism (CD) and hydrophobic dye
      binding. The parameter A and phase diagram analysis revealed multi-state
      unfolding and existence of three stable intermediates during guanidine
      hydrochloride (Gdn-HCl) induced unfolding of HRI (KD). The protein treated with 6
      M Gdn-HCl showed collisional and static mechanism of acrylamide quenching and the
      constants (K(sv) = 3.08 M(-1) and K(s)= 5.62 M(-1)) were resolved using time
      resolved fluorescence titration. Based on pH, guanidine hydrochloride and
      temperature mediated transitions, HRI (KD) appears to exemplify a rigid molten
      globule-like intermediate with compact secondary structure, altered tertiary
      structure and exposed hydrophobic patches at pH 3.0. The results indicate the
      inherent structural stability of HRI (KD), a member of the class of stress
      response proteins.

PMID- 21947570
TI  - A directed miniscreen for genes involved in the Drosophila anti-parasitoid immune
      response.
AB  - Drosophila larvae react against eggs from the endoparasitoid wasp Leptopilina
      boulardi by surrounding them in a multilayered cellular capsule. Once a wasp egg
      is recognized as foreign, circulating macrophage-like cells, known as
      plasmatocytes, adhere to the invader. After spreading around the wasp egg,
      plasmatocytes form cellular junctions between the cells, effectively separating
      the egg from the hemocoel. Next, a second sub-type of circulating
      immunosurveillance cell (hemocyte), known as lamellocytes, adhere to either the
      wasp egg or more likely the plasmatocytes surrounding the egg. From these events,
      it is obvious that adhesion and cell shape change are an essential part of
      Drosophila's cellular immune response against parasitoid wasp eggs. To date, very
      few genes have been described as being necessary for a proper anti-parasitization
      response in Drosophila. With this in mind, we performed a directed genetic
      miniscreen to discover new genes required for this response. Many of the genes
      with an encapsulation defect have mammalian homologues involved in cellular
      adhesion, wound healing, and thrombosis, including extracellular matrix proteins,
      cellular adhesion molecules, and small GTPases.

PMID- 21947571
TI  - [The patellofemoral joint].

PMID- 21947572
TI  - [The third compartment in knee endoprosthetics: from denervation to replacement,
      which therapy is correct?].
AB  - Involvement of the patellofemoral compartment is common in osteoarthritis of the
      knee but to date there is no consensus as to the most appropriate approach
      concerning the patella. Both general non-selective resurfacing as well as
      selective or secondary resurfacing are currently accepted. However, despite
      abundant studies on the subject no clear conclusions can be drawn from the
      available evidence. There are arguments in favour of either approach.
      Accordingly, no strong evidence can be found to support peripatellar denervation.
      With the advent of new diagnostic modalities for the assessment of knee
      osteoarthritis, such as single photon emission computed tomography/CT (SPECT/CT),
      a more selective approach to patellar resurfacing with a potentially improved
      outcome might become possible.

PMID- 21947573
TI  - Leiomyosarcomas of the oral cavity: report of a radiation-associated and a
      metastatic case.
AB  - BACKGROUND: Leiomyosarcoma is rare in the oral cavity, where it may arise as
      primary, radiation-associated, or metastatic tumor. This article reports two
      cases of oral leiomyosarcoma, discussing the range of clinicopathological
      features and the significance of these presentations. CASE REPORT: One case is a
      radiation-associated leiomyosarcoma arising in the tongue of a 71-year-old male
      occurring 22 years after radiation therapy for tonsil squamous cell carcinoma
      that was surgically treated. The other one is a mandible metastasis from a
      retroperitoneal widespread leiomyosarcoma in a 69-year-old man, who was treated
      by surgery and chemotherapy but died from the disease. DISCUSSION: Post
      radiotherapy sarcomas of the oral cavity and oral metastasis from soft tissue
      sarcomas are very uncommon, but based on patient's clinical history, they should
      be considered by oral health care providers in order to allow an early diagnosis
      and proper and timely management. Finally, to the best of our knowledge, this
      seems to be the first reported case of tongue leiomyosarcoma arising in a
      previously irradiated field.

PMID- 21947576
TI  - Central bisectionectomy (bisegmentectomy) of the liver (with video).
AB  - Surgical techniques and indications for central bisectionectomy (bisegmentectomy)
      of the liver, i.e., resection of Couinaud's segments 4, 5 and 8, are described.
      Parenchymal dissection between the left medial and lateral sections is performed
      by dividing Glisson's branches arising from the right side of the umbilical
      portion towards the confluence between the middle and left hepatic veins.
      Parenchymal dissection between the right anterior and posterior sections is
      performed along the demarcation line created by obliterating the Glisson's
      pedicle of the right anterior section (Couinaud's segments 5 and 8), and then
      along the left side of the right hepatic vein. The root of the middle hepatic
      vein is divided at the bottom of the right and left plane of the parenchymal
      division. The indications for central bisectionectomy include benign and
      malignant tumors occupying both the left medial and right anterior sections,
      i.e., Couinaud's segments 4, 5 and 8, while sparing the left lateral and right
      posterior sections, i.e., Couinaud's segments 2, 3, 6 and 7. This technique is
      advocated especially for liver tumors arising in chronic liver diseases such as
      hepatocellular carcinoma complicating viral hepatitis and metastatic liver tumor
      with concomitant steatosis of the non-cancerous liver parenchyma, for which right
      or left trisectionectomy could result in less than optimal remnant liver volume
      and function.

PMID- 21947574
TI  - Pregnancy and its management in women with GSD type III - a single centre
      experience.
AB  - We present a review of our experience and pregnancy outcome in patients with GSD
      III managed by our centre. Between 1997 and 2010 there were 15 pregnancies in
      seven women with GSD III. Four women had GSD IIIb (nine pregnancies) and three
      GSD IIIa (six pregnancies). There was a successful outcome in all 15 pregnancies
      with delivery of 15 liveborn infants. Four infants were of low birthweight (<2nd
      centile) but all have developed normally apart from one with
      behavioural/psychiatric problems. Three women had pre-existing cardiomyopathy
      prior to pregnancy. One of these women had deterioration of her cardiomyopathy
      during pregnancy and again in the post-partum period. Women with GSD III do not
      seem to have any issues with fertility. Overall the outcome of pregnancy for both
      mother and child is good. Care needs to be taken to avoid maternal hypoglycemia
      which may be associated with intrauterine growth restriction and low birth
      weight. Cardiac function should be monitored carefully particularly in those with
      pre-existing cardiomyopathy.

PMID- 21947577
TI  - [Acute macular neuroretinopathy].
AB  - A 24-year-old female patient presented with sudden onset of paracentral visual
      field defects of the right eye, which were noticed 2 months before the clinical
      examination. The slit lamp examination of the anterior and posterior segments
      showed unremarkable findings but three oval, well demarcated, hyporeflective
      areas were noticed in the right posterior pole in infrared fundus photographs. A
      similar small area was found in the left posterior pole. Optical coherence
      tomography (Cirrus OCT) showed a structural defect of the hyperreflective bands
      of the outer retina. The diagnosis of acute macular neuroretinopathy was made.

PMID- 21947578
TI  - Sleep and plasticity.
AB  - While there is ample agreement that the cognitive role of sleep is explained by
      sleep-dependent synaptic changes, consensus is yet to be established as to the
      nature of these changes. Some researchers believe that sleep promotes global
      synaptic downscaling, leading to a non-Hebbian reset of synaptic weights that is
      putatively necessary for the acquisition of new memories during ensuing waking.
      Other investigators propose that sleep also triggers experience-dependent,
      Hebbian synaptic upscaling able to consolidate recently acquired memories. Here,
      I review the molecular and physiological evidence supporting these views, with an
      emphasis on the calcium signaling pathway. I argue that the available data are
      consistent with sleep promoting experience-dependent synaptic embossing,
      understood as the simultaneous non-Hebbian downscaling and Hebbian upscaling of
      separate but complementary sets of synapses, heterogeneously activated at the
      time of memory encoding and therefore differentially affected by sleep.

PMID- 21947580
TI  - Electromagnetic-tracked biopsy under ultrasound guidance: preliminary results.
AB  - PURPOSE: This study was designed to evaluate the accuracy and safety of
      electromagnetic needle tracking for sonographically guided percutaneous liver
      biopsies. METHODS: We performed 23 consecutive ultrasound-guided liver biopsies
      for liver nodules with an electromagnetic tracking of the needle. A sensor placed
      at the tip of a sterile stylet (18G) inserted in a coaxial guiding trocar (16G)
      used for biopsy was localized in real time relative to the ultrasound imaging
      plane, thanks to an electromagnetic transmitter and two sensors on the ultrasound
      probe. This allows for electronic display of the needle tip location and the
      future needle path overlaid on the real-time ultrasound image. Distance between
      needle tip position and its electronic display, number of needle punctures,
      number of needle pull backs for redirection, technical success (needle positioned
      in the target), diagnostic success (correct histopathology result), procedure
      time, and complication were evaluated according to lesion sizes, depth and
      location, operator experience, and "in-plane" or "out-of-plane" needle approach.
      RESULTS: Electronic display was always within 2 mm from the real position of the
      needle tip. The technical success rate was 100%. A single needle puncture without
      repuncture was used in all patients. Pull backs were necessary in six patients
      (26%) to obtain correct needle placement. The overall diagnostic success rate was
      91%. The overall true-positive, true-negative, false-negative, and failure rates
      of the biopsy were 100% (19/19) 100% (2/2), 0% (0/23), and 9% (2/23). The median
      total procedure time from the skin puncture to the needle in the target was 30
      sec (from 5-60 s). Lesion depth and localizations, operator experience, in-plane
      or out-of-plane approach did not affect significantly the technical, diagnostic
      success, or procedure time. Even when the tumor size decreased, the procedure
      time did not increase. CONCLUSIONS: Electromagnetic-tracked biopsy is accurate to
      determine needle tip position and allows fast and accurate needle placement in
      targeted liver nodules.

PMID- 21947579
TI  - Skeletal muscle ATP turnover and single fibre ATP and PCr content during intense
      exercise at different muscle temperatures in humans.
AB  - The effect of temperature on skeletal muscle ATP turnover, pulmonary oxygen
      uptake and single fibre ATP and PCr content was studied during intense cycling
      exercise. Six healthy male subjects performed 6-min intense (Delta50%LT
      VO(2peak)) cycling, at 60 rpm, under conditions of normal (N) and elevated muscle
      temperature (ET). Muscle biopsies obtained from the vastus lateralis at rest, 2
      and 6 min were analysed for homogenate ATP, PCr, lactate and glycogen, allowing
      estimation of anaerobic ATP turnover. Freeze-dried single fibres from biopsies
      were characterised according to their myosin heavy chain composition (type I, IIA
      or IIAX) and analysed for ATP and PCr content. Pulmonary gas exchange was
      measured throughout. There was no difference in pulmonary oxygen uptake between
      the trials. The elevation of muscle temperature resulted in a lower (P < 0.05)
      PCr content, higher (P < 0.05) lactate content and greater (P < 0.05) anaerobic
      ATP turnover after 2 min of exercise. There was no effect of temperature on these
      measures at 6 min. In single fibres it was observed that in ET, there was a lower
      (P < 0.05) PCr content in type I fibres after 2 min with no differences between
      conditions after 6 min. The present study demonstrates that elevation of muscle
      temperature results in a greater anaerobic ATP turnover and type I fibre PCr
      degradation during the initial 2 min of intense exercise.

PMID- 21947581
TI  - Associations of mother's and father's parenting practices with children's
      observed social reticence in a competitive situation: a monozygotic twin
      difference study.
AB  - This study used the monozygotic (MZ) twin difference method to examine whether
      the unique environmental effects of maternal and paternal overprotection and
      hostility at the age of 30 months predict twins' observed social reticence in a
      competitive situation in kindergarten, while controlling for the effect of family
      wide influences, including genetic and shared environmental factors, family socio
      economical status and twin's birth weight. It was also examined whether these
      associations are moderated by parental depressive symptoms. Participants were 137
      MZ twin pairs who were part of an ongoing longitudinal study. Hierarchical linear
      regressions revealed that differences in maternal and paternal overprotection
      predicted differences in twins' social reticence, albeit only in boys.
      Differences in paternal hostile parenting predicted differences in girls'
      reticent behavior, but only when fathers showed high levels of depressive
      symptoms. Hence, overprotected boys, as well as girls confronted with father's
      hostility and depressive symptoms, may tend to withdraw rather than face the
      challenge when experiencing difficult social situations such as competition. The
      results from the present study suggest that targeting maladaptive maternal as
      well as paternal child-rearing practices and psychopathology early on may be
      useful for reducing later internalizing behavior in the offspring.

PMID- 21947582
TI  - Association between prenatal lead exposure and blood pressure in children.
AB  - BACKGROUND: Lead exposure in adults is associated with hypertension. Altered
      prenatal nutrition is associated with subsequent risks of adult hypertension, but
      little is known about whether prenatal exposure to toxicants, such as lead, may
      also confer such risks. OBJECTIVES: We investigated the relationship of prenatal
      lead exposure and blood pressure (BP) in 7- to 15-year-old boys and girls.
      METHODS: We evaluated 457 mother-child pairs, originally recruited for an
      environmental birth cohort study between 1994 and 2003 in Mexico City, at a
      follow-up visit in 2008-2010. Prenatal lead exposure was assessed by measurement
      of maternal tibia and patella lead using in vivo K-shell X-ray fluorescence and
      cord blood lead using atomic absorption spectrometry. BP was measured by mercury
      sphygmomanometer with appropriate-size cuffs. RESULTS: Adjusting for relevant
      covariates, maternal tibia lead was significantly associated with increases in
      systolic BP (SBP) and diastolic BP (DBP) in girls but not in boys (p-interaction
      with sex = 0.025 and 0.007 for SBP and DBP, respectively). Among girls, an
      interquartile range increase in tibia lead (13 MUg/g) was associated with 2.11
      mmHg [95% confidence interval (CI): 0.69, 3.52] and 1.60-mmHg (95% CI: 0.28,
      2.91) increases in SBP and DBP, respectively. Neither patella nor cord lead was
      associated with child BP. CONCLUSIONS: Maternal tibia lead, which reflects
      cumulative environmental lead exposure and a source of exposure to the fetus, is
      a predisposing factor to higher BP in girls but not boys. Sex-specific adaptive
      responses to lead toxicity during early-life development may explain these
      differences.

PMID- 21947583
TI  - Lumpectomy cavity shaved margins do not impact re-excision rates in breast cancer
      patients.
AB  - BACKGROUND: The benefits of taking shaved cavity margins (SCM) at the time of
      lumpectomy are unclear. We sought to determine if taking SCM decreases re
      excision rates by increasing the total breast tissue volume excised. METHODS: We
      undertook a retrospective review of breast cancer patients who underwent
      lumpectomy from 2004 to 2006. Patients were divided into three groups. Group 1
      had lumpectomy alone, group 2 had lumpectomy plus select (1-3) SCM, and group 3
      had lumpectomy plus complete (>=4) SCM. Pathologic findings and surgical outcomes
      were compared between groups. RESULTS: 773 cancers treated by lumpectomy were
      included in this study; 197 were in group 1, 130 were in group 2, and 446 were in
      group 3. The mean total volume of breast tissue excised in group 1 (106.6 cm(3))
      was significantly larger than the volume excised in groups 2 (79.3 cm(3)) and 3
      (76.3 cm(3)). Rates of re-excision and successful breast-conservation therapy
      (BCT) were not significantly different between groups. Despite a lower total
      volume of breast tissue excised in groups 2 and 3, there was no significant
      increase in locoregional recurrence rates (LRR) at median follow-up of 54 months.
      CONCLUSIONS: Taking additional SCM during lumpectomy resulted in a significantly
      lower overall volume of breast tissue excised, with no increase in LRR. Contrary
      to prior studies, we found that SCM did not decrease re-excision rates or impact
      the success of BCT. Therefore, the main advantage of taking SCM appears to be
      that less breast tissue is excised, which could potentially improve cosmetic
      outcomes.

PMID- 21947584
TI  - Additive risk of tumescent technique in patients undergoing mastectomy with
      immediate reconstruction.
AB  - BACKGROUND: The potential advantages of tumescent mastectomy technique have been
      increasingly discussed within the literature. However, there is concern that
      tumescent solution may also affect postoperative complication rates. This study
      evaluates patient outcomes following tumescent mastectomy and immediate implant
      reconstruction. METHODS: Retrospective review of 897 consecutive patients (1,217
      breasts) undergoing mastectomy with immediate implant reconstruction between
      4/1998 and 10/2008 at a single institution was performed. Demographic and
      operative factors, postoperative outcomes, and overall follow-up were recorded.
      Complications were categorized by type and end-outcome. Fisher's exact test,
      Student t-test, and multiple linear regression were used for statistical
      analysis. RESULTS: Tumescent (n = 332, 457 breasts) and nontumescent (n = 565,
      760 breasts) patients were clinically similar. Mean follow-up was 36.5 months.
      Regression analysis demonstrated that tumescent technique increased the risk of
      overall complications [odds ratio (OR) 1.36, 95% confidence interval (CI) 1.02
      1.81, p = 0.04]. In particular, nonoperative and operative complications (OR
      1.53, 95% CI 1.04-2.26, p = 0.04; OR 1.58, 95% CI 1.11-2.23, p = 0.01,
      respectively), and the rate of major mastectomy flap necrosis (OR 1.57, 95% CI
      1.05-2.35, p = 0.03) were significantly affected. In patients with other, more
      significant risk factors, tumescent technique had an additive effect on
      complication rates. Additionally, the majority of tumescent breast complications
      (78.6%, 81/103) had at least one other significant risk factor. CONCLUSIONS: Our
      review demonstrates that tumescent mastectomy with immediate implant
      reconstruction, although possessing distinct advantages, can increase
      postoperative complication rates. This additive effect is particularly apparent
      in patients with elevated complication risk at baseline. Choice of mastectomy
      technique should be made with careful consideration of patient comorbidities.

PMID- 21947585
TI  - Definitive diagnosis for high-risk breast lesions without open surgical excision:
      the Intact Percutaneous Excision Trial (IPET).
AB  - BACKGROUND: Open surgical excision (OSE) is generally recommended when image
      guided core-needle breast biopsy demonstrates a high-risk lesion (HRL). We
      evaluated intact percutaneous excision (IPEX) with standard radiologic and
      histologic criteria for definitive diagnosis of HRL, particularly atypical ductal
      hyperplasia (ADH). The primary aim is to confirm criteria associated with <2%
      risk for upgrade to carcinoma, equivalent to risk associated with Breast Imaging
      Reporting and Data System (BI-RADS) 3 lesions, for which imaging surveillance is
      considered sufficient. METHODS: In a prospective trial, 1,170 patients
      recommended for breast biopsy at 25 institutions received IPEX with a vacuum- and
      radiofrequency-assisted device. ADH patients in whom the imaged lesion had been
      removed and the lesion adequately centered for definitive characterization were
      designated as the potential surgical avoidance population (PSAP) before OSE.
      Subsequent OSE specimen pathology was compared with IPEX findings. RESULTS: In
      1,170 patients, 191 carcinomas and 83 (7%) HRL, including 32 ADH (3%), were
      diagnosed via IPEX. None of the 51 non-ADH HRL were upgraded to carcinoma on OSE
      (n = 24) or, if OSE was declined, on radiologic follow-up (n = 27). No ADH
      lesions meeting PSAP criteria (n = 10) were upgraded to carcinoma on OSE; 3 (14%)
      of 22 non-PSAP ADH lesions were upgraded to carcinoma on OSE. In summary, no
      upgrades to carcinoma were made in patients with non-ADH lesions who underwent
      IPEX or in ADH patients who had IPEX, met histologic and radiologic criteria, and
      underwent OSE or follow-up. CONCLUSION: IPEX combined with straightforward
      histologic and radiologic criteria and imaging surveillance constitutes
      acceptable management of image-detected HRL, including ADH.

PMID- 21947586
TI  - Variability in the quality of pathology reporting of margin status following
      breast cancer surgery.
AB  - BACKGROUND: Accurately determining margin status is important for breast cancer
      treatment. The College of American Pathologists (CAP) developed guidelines to
      standardize reporting of margin status. The aim of this study is to determine
      statewide concordance with CAP breast cancer reporting guidelines for margin
      status. METHODS: The Vermont Breast Cancer Surveillance System (VBCSS) tracks
      mammography-related services provided to all women treated for breast cancer at
      hospitals in Vermont. These data include accompanying pathology reports, which
      were analyzed for descriptions of margin status. The CAP protocols have both
      requirements and recommendations for margin status reporting. Reports were
      "minimally compliant" if they adhered to the requirements stated in the CAP
      protocols or "maximally compliant" if they included the recommended protocols in
      addition to those required. RESULTS: There were 2,016 reports that met the
      inclusion criteria. A total of 71.1% were minimally compliant and 37.3% were
      maximally compliant with the CAP guideline standards. There was a statistically
      significant rise in compliant reports, with minimally compliant reports
      increasing from 55.7% in 1998 to 79.3% in 2006, and maximally compliant reports
      rising from 4.7% in 1998 to 53.7% in 2006 (chi(2) trend test, P < 0.001) for both
      cohorts. CONCLUSIONS: Reporting of margin status in breast-conserving surgery
      varies widely. There is a significant rise in guideline compliance with margin
      status reporting from 1998 to 2006; however, overall compliance remains
      suboptimal. This study provides evidence to support the need for quality
      improvement measures in the implementation of CAP guidelines for reporting margin
      status following breast-conserving surgery.

PMID- 21947587
TI  - Radioactive seed localization for nonpalpable breast lesions: review of 1,000
      consecutive procedures at a single institution.
AB  - INTRODUCTION: Radioactive seed localization (RSL) is an alternative to wire
      localization for nonpalpable breast lesions, with reported lower rates of
      positive surgical margins. METHODS: A retrospective review of all consecutive RSL
      procedures performed at a single institution from 01/2003 through 10/2010 was
      conducted. RESULTS: One thousand RSL breast procedures were performed in 978
      patients. Indications for RSL included invasive carcinoma (52%), in situ
      carcinoma (22%), atypical hyperplasia (11%), and suspicious percutaneous biopsy
      findings (15%). A total of 1,148 seeds were deployed using image guidance, with
      76% placed >=1 day before surgery. Most procedures (86%) utilized one seed. A
      negative margin was achieved at the first operation in 97% of patients with
      invasive carcinoma and 97% of patients with ductal carcinoma in situ (DCIS). An
      additional 9% of patients with invasive carcinoma and 19% of patients with DCIS
      had close (<=2 mm) margins, and underwent re-excision. Sentinel lymph node biopsy
      was successfully performed in 99.8% of cases. Adverse events included 3 seeds
      (0.3%) not deployed correctly on first attempt and 30 seeds (2.6%) displaced from
      the breast specimen during excision of the targeted lesion. All seeds were
      successfully retrieved, with no radiation safety concerns. Local recurrence rates
      were 0.9% for invasive breast cancer and 3% for DCIS after mean follow-up of 33
      months. There was no evidence of a learning curve. CONCLUSIONS: RSL is a safe,
      effective procedure that is easy to learn, with a low incidence of positive/close
      margins. RSL should be considered as the method of choice for localization of
      nonpalpable breast lesions.

PMID- 21947588
TI  - Prophylactic and therapeutic mastectomy in BRCA mutation carriers: can the nipple
      be preserved?
AB  - BACKGROUND: Use of nipple-sparing mastectomy (NSM) is increasing. We sought to
      look at the role of NSM in BRCA mutation carriers. METHODS: Tissue from women
      with a BRCA1 or BRCA2 mutation who underwent mastectomy between March 1987 and
      June 2009 at a single institution was reviewed. The entire nipple-areolar complex
      (NAC) was excised and histologically evaluated. The presence of terminal duct
      lobular units (TDLUs) and premalignant or malignant lesions in the NAC was noted.
      RESULTS: Sixty-two NACs from 33 women (25 BRCA1, 8 BRCA2) were studied. TDLUs
      were present in 15 (24%) NAC specimens. No evidence of atypical hyperplasia,
      carcinoma in situ, or invasive carcinoma was found in any of the 33 prophylactic
      mastectomy specimens. Among the 29 breasts with cancer and available tissue, 2
      (7%) had malignant findings and 1 (3%) had atypia in the NAC. One woman who
      underwent bilateral mastectomy for bilateral invasive carcinoma had one nipple
      with tumor within lymphatics, and her contralateral nipple had atypical lobular
      hyperplasia. A second woman had ductal carcinoma in situ involving a single major
      lactiferous duct. CONCLUSIONS: The probability of nipple involvement by
      premalignant or malignant lesions in the NAC of BRCA mutation carriers is low at
      time of prophylactic mastectomy, but higher (10%) in women undergoing therapeutic
      mastectomy. NSM may be appropriate and oncologically safe for selected women with
      BRCA mutations. However, 24% of NACs contained TDLUs, with only 8% found in the
      nipple papilla; the significance of this for long-term risk is unknown.

PMID- 21947589
TI  - Contralateral prophylactic mastectomy: long-term consistency of satisfaction and
      adverse effects and the significance of informed decision-making, quality of
      life, and personality traits.
AB  - PURPOSE: This study aims to evaluate the long-term consistency of satisfaction
      with contralateral prophylactic mastectomy (CPM) and adverse psychosocial effects
      as well as to explore the effect of informed decision-making, personality traits,
      and quality of life (QOL) on satisfaction. METHODS: A previously established
      cohort of women with unilateral breast cancer who had undergone CPM between 1960
      and 1993 were surveyed using study-specific and standardized questionnaires at
      two follow-up time points. The first survey was a mean of 10.7 years and the
      second survey a mean of 20.2 years after CPM. RESULTS: 487 of the 583 women who
      responded to the first study were alive and resurveyed. Data from both surveys
      were available for 269 women. With longer follow-up, there was a small increase
      in the percentage of women satisfied (90%) and those who would choose CPM again
      (92%) (4% and 2% increase from first survey, respectively). Most adversely
      affected were body appearance (31%), feelings of femininity (24%), and sexual
      relationships (23%). Ninety-three percent of women felt they had made an informed
      decision. Perception of making an informed choice and current QOL were moderately
      associated with satisfaction with CPM (r = 0.37 and 0.37, respectively) while
      associations with trait anxiety and optimism were weak (r = 0.27 and 0.21,
      respectively). CONCLUSIONS: Long-term satisfaction and adverse effects remained
      remarkably stable. It is important that women fully understand the benefits and
      adverse effects associated with CPM.

PMID- 21947590
TI  - Perceptions of contralateral breast cancer: an overestimation of risk.
AB  - INTRODUCTION: The rate of contralateral prophylactic mastectomy (CPM) has
      recently increased. The aim of this study is to assess perceptions of
      contralateral breast cancer (CBC) risk among breast cancer patients and to
      evaluate tumor and patient factors associated with risk perception. METHODS: We
      conducted a prospective survey study to evaluate perceptions of CBC risk in women
      newly diagnosed with ductal carcinoma in situ (DCIS) or stage I/II invasive
      breast cancer. Surveys were distributed in clinic prior to surgical consultation.
      Exclusion criteria included history of breast cancer, bilateral breast cancer,
      neoadjuvant chemotherapy or radiation for the current breast cancer, or BRCA
      mutation. Survey questions used open-ended responses or five-point Likert scale
      scoring (5 = very likely, 1 = not at all likely). RESULTS: Seventy-four women
      (mean age 54.5 years) completed the survey. Diagnoses included invasive ductal
      cancer (66.2%), invasive lobular cancer (9.5%), and DCIS (20.3%). Most women
      (54.1%) underwent breast-conserving surgery; the remaining had bilateral
      mastectomy including CPM (17.6%) or unilateral mastectomy (10.8%). Overall, women
      substantially overestimated their risk of developing CBC. The mean estimated 10
      year risk of CBC was 31.4% [95% confidence interval (CI) 24.7-37.9%] and 2.6 +/-
      0.15 on the rank scale. The perceived risk of CBC was not significantly
      associated with cancer stage, family history, age, or CPM. CONCLUSIONS: At time
      of surgical evaluation, women with unilateral breast cancer substantially
      overestimated their risk of CBC; however, this elevated risk perception was not
      associated with choosing CPM. Early physician counseling is needed to provide
      women with accurate information regarding their true CBC risk.

PMID- 21947591
TI  - Potential impact of USPSTF recommendations on early diagnosis of breast cancer.
AB  - OBJECTIVE: Current US Preventive Services Task Force (USPSTF) guidelines
      recommend against routine screening mammography in women aged 40-49 years.
      However, diagnosis of early-stage breast cancer relies on mammographic screening
      for detection. We hypothesized that screening at younger age may be important for
      detecting earlier and more treatable cancers for women in different demographic
      groups. METHODS: All women with ductal carcinoma in situ (DCIS) or T1N0 breast
      cancer between 2004 and 2008 in the California Cancer Registry were evaluated.
      Patients were divided into: (1) women aged 40-49 years, who would be excluded
      from USPSTF recommendations for screening, and (2) women aged 50-74 years, who
      are recommended for screening. Patients in the two age groups were compared by
      race/ethnicity, socioeconomic status (SES), and hormone receptor (HR), human
      epidermal growth factor receptor 2 (HER-2), and triple-negative (TN) status.
      RESULTS: Of 46,691 patients identified, 22.6% were aged 40-49 years, and 77.4%
      were aged 50-74 years. Younger women with DCIS had statistically higher odds of
      being HR positive and having higher SES, and Hispanic and Asian/Pacific Islander
      (PI) race/ethnicity, while younger women diagnosed with T1N0 breast cancer had
      higher odds of being HR positive, HER-2 positive, and triple negative and of
      having higher SES and non-white race/ethnicity. CONCLUSIONS: Young Hispanic,
      Asian/PI, and non-Hispanic (NH) Black women in California have greater odds of
      being diagnosed with early breast cancer than their older counterparts. Excluding
      40-49-year-old women from screening could impact early diagnosis of HR-positive,
      HER-2-positive, and TN tumors. Implementation of USPSTF recommendations could
      disproportionately impact non-white women and potentially lead to more advanced
      presentation at diagnosis.

PMID- 21947592
TI  - MRI staging after neoadjuvant chemotherapy for breast cancer: does tumor biology
      affect accuracy?
AB  - BACKGROUND: A discrepancy often exists between the post-neoadjuvant chemotherapy
      (NAC) breast tumor size on magnetic resonance imaging (MRI) and pathologic tumor
      size. We seek to quantify this MRI/pathology discrepancy and determine if the
      accuracy of MRI post NAC varies with tumor subtype. METHODS: The University of
      Pittsburgh Medical Center (UPMC) Cancer Registry and radiology database were
      searched for patients with breast cancer who underwent NAC and MRI staging
      between 2004 and 2009. We compared radiologic to pathologic staging and
      stratified differences based on tumor biology using univariate, multivariate, and
      receiver operating characteristic (ROC) analysis. RESULTS: Two hundred three of
      592 patients undergoing surgery after NAC for breast cancer had MRI staging pre
      and post chemotherapy. All patients had intact tumors prior to the initiation of
      chemotherapy. Average tumor size by MRI was 4.0 cm pre chemotherapy and 1.2 cm
      post chemotherapy. The average pathologic tumor size was 1.7 cm (range 0-13 cm).
      The difference between MRI and pathologic tumor size was greatest in luminal (1.1
      cm) and least in triple-negative (TN) and human epidermal growth factor receptor
      2 (HER2)-positive tumors (<0.1 cm) (p = 0.015). MRI was a good discriminator for
      pathologic complete response (pCR) [area under the curve (AUC) 0.777]. Its
      predictive value for pCR was much greater in TN and estrogen receptor(ER)-/HER2+
      than in luminal tumors (73.6 vs. 27.3%). CONCLUSIONS: MRI is an effective tool
      for predicting response to NAC. The accuracy of MRI in estimating
      postchemotherapy tumor size varies with tumor subtype. It is highest in ER-/HER2+
      and TN and lowest in luminal tumors. Knowledge of how tumor subtype affects MRI
      accuracy can guide recommendations for surgery following NAC.

PMID- 21947593
TI  - Margin index is not a reliable tool for predicting residual disease after breast
      conserving surgery for DCIS.
AB  - OBJECTIVE: We previously introduced the concept of margin index as a method for
      prediction of residual disease after attempted breast-conserving therapy (BCT).
      We sought to apply the margin index to patients with ductal carcinoma in situ
      (DCIS) to determine its reliability in predicting residual disease. METHODS: We
      identified all patients with DCIS who were treated with BCT from 2004 to 2010.
      Margin index was calculated as follows: margin index = closest margin (mm)/tumor
      size (mm) * 100. A receiver operating curve was created using the derived margin
      index and the presence or absence of residual disease in the re-excision
      specimen. Sensitivity and specificity were calculated at various margin indices
      to identify the optimum margin index. RESULTS: Of 380 patients undergoing
      attempted BCT, 109 (29%) underwent re-excision. Of 109 patients undergoing re
      excision, 46 (42%) had positive margins and were excluded from the study, 15
      (14%) were excluded due to inability to determine the size of DCIS on pathology
      reports, and 48 (44%) met study criteria and were included in the analysis. Of 48
      patients undergoing re-excision, 19 (40%) had residual disease. The receiver
      operating curve c index was 0.65. However, there was no optimum margin index that
      reliably predicted the presence or absence of residual disease. CONCLUSIONS:
      Margin index is not a reliable method for prediction of residual disease after
      attempted BCT with close margins in patients with DCIS only. This may be a
      reflection of the complexities in accurately determining DCIS size and margin
      status in pathologic specimens.

PMID- 21947594
TI  - Accuracy of clinical examination, digital mammogram, ultrasound, and MRI in
      determining postneoadjuvant pathologic tumor response in operable breast cancer
      patients.
AB  - BACKGROUND: To determine the accuracy, positive predictive value (PPV), and
      negative predictive value (NPV) of clinical examination and breast imaging
      techniques in determining pathologic complete response in patients with locally
      advanced breast cancer after neoadjuvant therapy. METHODS: A retrospective review
      was performed of data collected from patients treated with either neoadjuvant
      hormonal or chemotherapy between January 2005 and September 2010. Patients were
      evaluated by one of three surgical breast oncologists before neoadjuvant therapy
      and within 1 month before surgery by clinical breast examination (CBE), digital
      mammogram, breast ultrasound, and/or magnetic resonance imaging (MRI). The
      accuracy, NPV, and PPV of each modality was calculated on the basis of the final
      pathologic report. Available data from the literature was synthesized. RESULTS:
      Sixty-two tumors in 61 patients with a mean age of 56 (range 34-87) years were
      evaluated. Overall accuracy ranged from 54% (CBE) to 80% (breast ultrasound). All
      modalities had a PPV greater than 75% for identifying the presence of residual
      disease. The PPV of each modality was generally higher in the younger patients.
      The NPV of all methods was less than 50%. The accuracy and NPV were compromised
      even further in younger patients. The combination of our own data with data
      available from the literature revealed MRI to be superior with regard to accuracy
      and PPV, but the NPV of MRIs remained poor at 65%. CONCLUSIONS: All measured
      tests are good at predicting the presence of disease on final pathology, but none
      are able to reliably predict a pathologic complete response.

PMID- 21947596
TI  - Single monthly bacillus Calmette-Guerin intravesical instillation is effective
      maintenance therapy to prevent recurrence in Japanese patients with non-muscle
      invasive bladder cancer.
AB  - BACKGROUND: A series of bacillus Calmette-Guerin (BCG) bladder instillations is
      the gold standard therapy to prevent recurrence after transurethral resection of
      bladder tumor (TUR-Bt) of non-muscle-invasive bladder cancer (NMIBC). However, in
      some cases the outcome is not optimal with the standard 6- to 8-week protocol and
      therefore interest has focused on additional maintenance therapy. The present
      study was conducted to assess the utility of single monthly intravesical
      instillation treatments for up to 1 year in Japanese patients. METHODS: A total
      of 75 stage Ta and T1 patients who had undergone TUR-Bt were retrospectively
      evaluated, all first receiving 80 mg BCG (Tokyo 172 strain) given once a week, 6
      8 times, for primary prophylaxis. Comparison was then made of groups with (group
      A, 48 patients) and without (group B, 27 patients) additional maintenance BCG
      therapy given once a month 6-8 times. RESULTS: Recurrence-free survival rates at
      5 years in groups A and B were 83.0 and 51.9% (P = 0.006), despite the greater
      proportion of T1 patients and the longer follow-up period in the group A
      patients. Significant protection against recurrence persisted on multivariate
      analysis with adjustment for age, stage, grade, and tumor number. CONCLUSIONS:
      These findings indicate maintenance BCG therapy of single intravesical
      instillations given once a month with our protocol to be definitely effective for
      prophylactic use, especially in stage Ta patients. Further evaluation of
      parameters such as the continuance period and dose protocol is warranted.

PMID- 21947595
TI  - Triple-negative breast cancer is not a contraindication for breast conservation.
AB  - BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive subtype shown
      to have a high risk of locoregional recurrence (LRR). The purpose of this study
      was to determine the impact of operation type on LRR in TNBC patients. METHODS: A
      total of 1325 patients with TNBC who underwent breast-conserving therapy (BCT) or
      mastectomy from 1980 to the present were identified. Clinical and pathological
      factors were compared by the chi-square test. LRR-free survival (LRRFS), distant
      metastasis-free survival, and overall survival were estimated by the Kaplan-Meier
      method. Multivariate analysis was performed by the Cox proportional hazard
      models. RESULTS: BCT was performed in 651 patients (49%) and mastectomy in 674
      (51%). The mastectomy group had larger tumors, a higher incidence of
      lymphovascular invasion, and higher pathologic N stage (all P < 0.001). At 62
      month median follow-up, LRR was seen in 170 (26%) in the BCT group and 203 (30%)
      in the mastectomy group. Five-year LRRFS rates were higher in the BCT group (76%
      vs. 71%, P = 0.032), as was distant metastasis-free survival (68% vs. 54%, P <
      0.0001) and overall survival (74% vs. 63%, P < 0.0001). On multivariate analysis,
      T stage (hazard ratio [HR] 1.37, P = 0.006), high nuclear grade (HR 1.92, P =
      0.002), lymphovascular invasion (HR 1.93, P < 0.0001), close/positive margins (HR
      1.89, P < 0.0001), and use of non-anthracycline or taxane-based adjuvant
      chemotherapy (HR 2.01, P < 0.0001) increased the LRR risk, while age >50 years
      was protective (HR 0.73, P = 0.007). Operation type (mastectomy vs. BCT, HR 1.07,
      P = 0.55) was not statistically significant. CONCLUSIONS: BCT is not associated
      with increased LRR rates compared to mastectomy. TNBC should not be considered a
      contraindication for breast conservation.

PMID- 21947597
TI  - Successful treatment of Kasabach-Merritt syndrome arising from kaposiform
      hemangioendothelioma by systemic corticosteroid therapy and surgery.
AB  - Kasabach-Merritt syndrome is a rare type of vascular tumor with aggressive
      behavior in association with thrombocytopenia and consumptive coagulopathy. A
      standard guideline has not been established to date. A 7-day-old male infant with
      Kasabach-Merritt syndrome arising from kaposiform hemangioendothelioma was
      successfully treated with systemic corticosteroid and surgery. Systemic
      corticosteroid including methylprednisolone was injected intravenously followed
      by an intralesional injection of compound betamethasone. This approach brought
      about an excellent response after the first treatment which was maintained long
      enough to provide us with an opportunity to excise the tumor. Systemic
      corticosteroid and surgery may be considered an option for Kasabach-Merritt
      syndrome, although well-designed studies are needed to quantify the benefits and
      risks of this treatment.

PMID- 21947598
TI  - Cigarette smoke stimulates VEGF-C expression in cervical intraepithelial
      neoplasia (CIN) 1 and 2 lesions.
AB  - OBJECTIVE: Vascular endothelial growth factors (VEGFs) are involved in
      angiogenesis, but molecular links to the most important etiological agents, human
      papillomavirus (HPV) and smoking, need to be clarified. METHODS: Archival samples
      at the first diagnosis of 64 cervical intraepithelial neoplasia grade 1 or 2 (CIN
      1/2) lesions were examined immunohistochemically using anti-VEGF-C and anti-Ki-67
      antibodies. HPV types were identified from cervical samples by restriction
      fragment length polymorphism, which has been shown to identify at least 26 types
      of genital HPVs. Follow-up data were available for all patients with CIN lesions.
      RESULTS: Cervical intraepithelial neoplasia lesions regressed in 47 cases and
      were persistent in 17 cases. Twenty-two smokers, 8 former smokers, and 34 non
      smokers were enrolled in the study. The median observation period was 52.3
      months. Significantly higher VEGF-C expression was observed in 8 smokers with
      persistent CIN persistence (49.0 +/- 16.6%, P < 0.01), whereas no significant
      difference was observed in Ki-67 expression. The median time to regression was
      significantly longer in the 10 smokers with high VEGF-C expression (48.3 months,
      P = 0.030) than that in the others. HPV was detected in 56 of the 64 cases.
      Thirty-two patients had high-risk HPV, 13 had intermediate-risk HPV, and 2 had
      low-risk HPV. No significant difference was observed among the HPV risk groups in
      both average Ki-67 and VEGF-C expression. CONCLUSIONS: These findings suggest
      that VEGF-C may play an important role in cigarette smoking-associated cervical
      carcinogenesis.

PMID- 21947599
TI  - An extended 15 Hz ERG protocol (2): data of normal subjects and patients with
      achromatopsia, CSNB1, and CSNB2.
AB  - The amplitude versus flash strength curve of 15 Hz electroretinograms (ERGs)
      shows two minima. The minima are caused by interactions between the primary and
      the secondary rod pathways (first minimum), and the secondary rod pathway and the
      cone-driven pathway (second minimum). Furthermore, cone pathway contributions
      cause higher-order harmonics to occur in the responses. We measured 15 Hz ERGs in
      20 healthy subjects to determine normal ranges and in patients to verify our
      hypotheses on the contributions of the different pathways and to investigate the
      clinical application. We analyzed the amplitudes and phases of the 15, 30, and 45
      Hz components in the ERGs. The overall shape of the 15 Hz amplitude curves was
      similar in all normal subjects and showed two minima. The 30 and 45 Hz amplitude
      curves increased for stimuli of high flash strengths indicating cone pathway
      contributions. The 15 Hz amplitude curve of the responses of an achromat was
      similar to that of the normal subjects for low flash strengths and showed a
      minimum, indicating normal primary and secondary rod pathway function. There was
      no second minimum, and there were no higher-order harmonics, consistent with
      absent cone pathway function. The 15 Hz ERGs in CSNB1 and CSNB2 patients were
      similar and of low amplitude for flash strengths just above where the first
      minimum normally occurs. We could determine that in the CSNB1 patients, the
      responses originate from the cone pathway, while in the CSNB2 patients, the
      responses originate from the secondary rod pathway.

PMID- 21947600
TI  - Immobilization of cellulase from newly isolated strain Bacillus subtilis TD6
      using calcium alginate as a support material.
AB  - Bacillus subtilis TD6 was isolated from Takifugu rubripes, also known as puffer
      fish. Cellulase from this strain was partially purified by ammonium sulphate
      precipitation up to 80% saturation, entrapped in calcium alginate beads, and
      finally characterized using CMC as the substrate. For optimization, various
      parameters were observed, including pH maximum, temperature maximum, sodium
      alginate, and calcium chloride concentration. pH maximum of the enzyme showed no
      changes before and after immobilization and remained stable at 6.0. The
      temperature maximum showed a slight increase to 60  degrees C. Two percent sodium
      alginate and a 0.15 M calcium chloride solution were the optimum conditions for
      acquisition of enzyme with greater stability. K (m) and V (max) values for the
      immobilized enzyme were slightly increased, compared with those of free enzyme,
      2.9 mg/ml and 32.1 MUmol/min/mL, respectively. As the purpose of immobilization,
      reusability and storage stability of the enzyme were also observed. Immobilized
      enzyme retained its activity for a longer period of time and can be reused up to
      four times. The storage stability of entrapped cellulase at 4  degrees C was
      found to be up to 12 days, while at 30  degrees C, the enzyme lost its activity
      within 3 days.

PMID- 21947601
TI  - Different environmental temperatures affect amino acid metabolism in the
      eurytherm teleost Senegalese sole (Solea senegalensis Kaup, 1858) as indicated by
      changes in plasma metabolites.
AB  - Senegalese sole (Solea senegalensis) is a eurytherm teleost that under natural
      conditions can be exposed to annual water temperature fluctuations between 12 and
      26 degrees C. This study assessed the effects of temperature on sole metabolic
      status, in particular in what concerns plasma free amino acid changes during
      thermal acclimation. Senegalese sole maintained at 18 degrees C were acclimated
      to either cold (12 degrees C) or warm (26 degrees C) environmental temperatures
      for 21 days. Fish maintained at 18 degrees C served as control. Plasma
      concentrations of cortisol, glucose, lactate, triglycerides, proteins, and free
      amino acids were assessed. Cold acclimation influenced interrenal responses of
      sole by increasing cortisol release. Moreover, plasma glucose and lactate
      concentrations increased linearly with temperature, presumably reflecting a
      higher metabolic activity of sole acclimated to 26 degrees C. Acclimation
      temperature affected more drastically plasma concentrations of dispensable than
      that of indispensable amino acids, and different acclimation temperatures induced
      different responses. Asparagine, glutamine and ornithine seem to be of particular
      importance for ammonia detoxification mechanisms, synthesis of triglycerides that
      may be used during homeoviscous adaptation and, to a lesser extent, as energetic
      substrates in specimens acclimated to 12 degrees C. When sole is acclimated to 26
      degrees C taurine, glutamate, GABA and glycine increased, which may suggest
      important roles as antioxidant defences, in osmoregulatory processes and/or for
      energetic purposes at this thermal regimen. In conclusion, acclimation to
      different environmental temperatures induces several metabolic changes in
      Senegalese sole, suggesting that amino acids may be important for thermal
      acclimation.

PMID- 21947603
TI  - Caudate lobectomy (segmentectomy 1) (with video).
AB  - BACKGROUND: The caudate lobe of the liver is located behind both major lobes and
      is surrounded by the inferior vena cava, three main hepatic veins, and the
      hepatic hilum. Despite a hard-to-approach anatomic location, isolated complete
      removal of the caudate lobe is recommended to improve curability in
      hepatocellular carcinoma (HCC). This is because most patients with HCC cannot
      undergo caudate lobectomy (segmentectomy 1) with resection of adjacent liver
      regions due to their poor liver function. METHODS: We performed an anatomic
      isolated caudate lobectomy using a high dorsal resection technique in patients
      with HCC involving the paracaval portion of the liver. In this procedure, the
      caudate lobe is dissected, the boundary of the caudate lobe is identified using
      counterstaining and tattooing techniques, and the liver is transected along
      landmarks. The caudate lobe can be removed completely, without loss of the
      parenchyma of the major lobes, thereby preserving liver function. CONCLUSIONS:
      Given that most patients with HCC concurrently have chronic liver disease, those
      with HCC in the caudate lobe are good candidates for high dorsal resection of the
      liver, which is safe, potentially curative procedure.

PMID- 21947602
TI  - A cross-species comparison of escape from X inactivation in Eutheria:
      implications for evolution of X chromosome inactivation.
AB  - Sex chromosome dosage compensation in both eutherian and marsupial mammals is
      achieved by X chromosome inactivation (XCI)--transcriptional repression that
      silences one of the two X chromosomes in the somatic cells of females. We
      recently used RNA fluorescent in situ hybridization (FISH) to show, in individual
      nuclei, that marsupial X inactivation (in the absence of XIST) occurs on a gene
      by-gene basis, and that escape from inactivation is stochastic and independent of
      gene location. In the absence of similar data from fibroblast cell lines of
      eutherian representatives, a meaningful comparison is lacking. We therefore used
      RNA-FISH to examine XCI in fibroblast cell lines obtained from three distantly
      related eutherian model species: African savannah elephant (Loxodonta africana),
      mouse (Mus musculus) and human (Homo sapiens). We show that, unlike the
      orthologous marsupial X, inactivation of the X conserved region (XCR) in
      eutherians generally is complete. Two-colour RNA-FISH on female human, mouse and
      elephant interphase nuclei showed that XCR loci have monoallelic expression in
      almost all nuclei. However, we found that many loci located in the evolutionarily
      distinct recently added region (XAR) displayed reproducible locus-specific
      frequencies of nuclei with either one or two active X alleles. We propose that
      marsupial XCI retains features of an ancient incomplete silencing mechanism that
      was augmented by the evolution of the XIST gene that progressively stabilized the
      eutherian XCR. In contrast, the recently added region of the eutherian X displays
      an incomplete inactivation profile similar to that observed on the evolutionarily
      distinct marsupial X and the independently evolved monotreme X chromosomes.

PMID- 21947604
TI  - Branched-chain amino acid-enriched nutrients improve nutritional and metabolic
      abnormalities in the early post-transplant period after living donor liver
      transplantation.
AB  - BACKGROUND/PURPOSE: Malnutrition and metabolic disorder of patients undergoing
      living donor liver transplantation (LDLT) can affect post-transplant prognosis.
      The aim of this study was to establish whether perioperative usage of branched
      chain amino-acid (BCAA)-enriched nutrients improve metabolic abnormalities of
      patients undergoing LDLT. METHODS: We designed a randomized pilot study (UMIN
      registration number; 000004323). Twenty-five consecutive adult elective LDLT
      recipients were enroled and divided into two groups: the BCAA group (BCAA
      enriched nutrients, n = 12) and the control group (standard diet, n = 13).
      Metabolic and nutritional parameters, including BCAA-to-tyrosine ratio (BTR),
      retinol binding protein (RBP), and prealbumin were regularly measured from 1 week
      before to 4 weeks after LDLT. Non-protein respiratory quotient (npRQ) was
      measured before and 4 weeks after LDLT. RESULTS: BTR and RBP improved
      considerably in the BCAA group compared with the controls. npRQ significantly
      increased from 1 week before LDLT to 4 weeks after LDLT in the BCAA group (0.77
      +/- 0.05 to 0.84 +/- 0.06, P = 0.002), but not in the control group (0.78 +/-
      0.04 to 0.81 +/- 0.05). CONCLUSIONS: Supplementation with BCAA-enriched nutrients
      might improve persistent nutritional and metabolic disorders associated with end
      stage liver disease in the early post-transplant period, and consequently shorten
      the post-transplant catabolic phase after LDLT. A larger multicenter trial is
      needed to confirm these findings.

PMID- 21947605
TI  - Anthrahydroquinone-2,6,-disulfonate (AH2QDS) increases hydrogen molar yield and
      xylose utilization in growing cultures of Clostridium beijerinckii.
AB  - H(2) production and xylose utilization were investigated using the fermentative
      culture Clostridium beijerinckii NCIMB 8052. Adding anthrahydroquinone-2,6
      disulfonate (AH(2)QDS) increased the extent of xylose utilization by 56% and
      hydrogen molar yield by 24-37%. Enhanced hydrogen molar yield correlated with
      increased xylose utilization and increases in the acetate/butyrate product ratio.
      An electron balance indicated that AH(2)QDS shifted the electrons from the
      butyric acid pathway (NADH-dependent pathway) to the acetic acid pathway (non
      NADH-dependent pathway), putatively creating a surplus of reducing equivalents
      that were then available for hydrogen production. These data demonstrate that
      hydrogen yield and xylose utilization can be manipulated by amending redox active
      molecules into growing cultures. This will impact biohydrogen/biofuel production
      by allowing physiological manipulations of growing cells for increased (or
      decreased) output of selected metabolites using amendments that are not consumed
      during the reactions. Although the current yield increases are small, they
      suggest a target for cellular alterations. In addition, increased xylose
      utilization will be critical to the fermentation of pretreated lignocellulosic
      feedstocks, which may have higher xylose content.

PMID- 21947606
TI  - [Patellofemoral pain after total knee arthroplasty: clinical pathway and review
      of the literature].
AB  - Total knee arthroplasty (TKA) is an operation with a high gain in quality of
      life. However, some patients suffer from pain, limited range of motion,
      instability, infections or other postoperative complications. Patellofemoral pain
      (PFP) in particular is a common complication after TKA and is often responsible
      for revision surgery. In particular increasing and localized contact pressure and
      patella maltracking are held accountable for patellofemoral pain but the reasons
      are various. Diagnostics and therapy of patellofemoral pain is not easy to handle
      and should be treated following a clinical pathway. We suggest that patients with
      patellofemoral pain should be classified into four groups according to the
      suspected diagnosis after basic diagnostic measures as 1) tenidinosis, 2)
      mechanical reasons, 3) intraarticular non-mechanical reasons and 4) neurogenic
      psychogenic reasons. Efficient application of special diagnostic measures and
      further therapy is facilitated by this classification.

PMID- 21947607
TI  - Cross-sectional relationship of a Mediterranean type diet to diastolic heart
      function in chronic heart failure patients.
AB  - Systolic and diastolic functions of both ventricles play a crucial role in the
      progression of chronic heart failure (CHF). As data about the role of dietary
      habits in ventricular dysfunction are lacking, we aimed to evaluate the
      relationship between biventricular diastolic and systolic function and dietary
      habits in patients with CHF. During 2007, 372 consecutive CHF patients were
      enrolled. Biventricular systolic and diastolic function was evaluated through
      echocardiography. Dietary habits were recorded using a food frequency
      questionnaire, and adherence to a Mediterranean diet was evaluated using the
      MedDietScore. The MedDietScore was positively correlated with log Smv, left
      atrial EF and V (p), and inversely correlated with log EA and log Emv/Amv levels
      (p < 0.05). After adjusting for potential confounders, only log E/A levels were
      inversely associated with the MedDietScore (p < 0.05). Following analysis per
      specific aliments, the log E/A ratio was inversely associated with fish intake
      and olive oil use; the log Emv/Amv ratio was inversely associated with fish
      intake; log Stv was positively associated with fish, olive oil and pasta intake;
      log LAKE was positively associated with olive oil use and alcohol drinking (all p
      < 0.05). This study demonstrated, in a cross-sectional design, a potential
      beneficial effect of a Mediterranean diet on biventricular systolic and diastolic
      function.

PMID- 21947608
TI  - A promising CdSe@CdS-quantum dots-cysteine for the determination of trace IgE by
      solid substrate room temperature phosphorescence immunoassay.
AB  - The labelling reagent CdSe@CdS-QDs-Cys (QDs-Cys) with the grain diameter of 4.5
      nm was synthesized by modifying CdSe@CdS quantum dots (QDs) with cysteine (Cys).
      At the same time, QDs-Cys-Ab(IgE), a phosphorescent quantum dot probe, was
      developed based on the labelling reaction between -COOH of QDs-Cys and -NH(2) of
      goat anti human IgE antibody (Ab(IgE)). This probe with excellent
      biocompatibility and high specificity could not only emit strong and stable room
      temperature phosphorescence (RTP), but also could carry out specific immunoassay
      (IA) with immunoglobulin E (IgE), causing the RTP of the system to sharply
      enhance. Thus, a new solid substrate room temperature phosphorescence immunoassay
      (SSRTPIA) for the determination of IgE was established. The limit of
      quantification (LOQ) of the method was 0.12 fg spot(-1), corresponding
      concentration was 3.0 * 10(-13) g mL(-1) and sampling quantity was 0.40 MUL spot(
      1). This highly selective, sensitive and accurate SSRTPIA has been applied to
      determine IgE in biological samples and diagnose diseases, and the results agreed
      well with those obtained by enzyme-link immunoassay (ELISA). Meanwhile, the
      mechanisms of QDs-Cys labelling Ab(IgE) and the determination of IgE by SSRTPIA
      were also discussed.

PMID- 21947610
TI  - Cool white light emission in dysprosium and salicylic acid doped poly vinyl
      alcohol film under UV excitation.
AB  - Dysprosium (Dy) and Salicylic acid (Sal) doped Poly Vinyl Alcohol (PVA) films
      have been successfully prepared by solution cast technique. The absorption,
      excitation, emission and lifetime analysis of the samples have been carried out.
      Judd-Ofelt theory has been used to estimate several parameters for DyCl(3) and
      Dy(Sal)(3)Phen in PVA polymer film which show fair agreement between the
      experimental and the theoretical values supporting the J-O theory. A combination
      of blue and yellow emissions in Dy(x)(Sal)(3)Phen co-doped PVA samples makes one
      perceive cool white light when excited by ultraviolet light. Energy transfer (ET)
      from Sal to Dy(3+) is investigated by directly observing the luminescence
      intensity of Dy(3+) in the Dy(x)(Sal)(3)Phen co-doped PVA samples which is much
      stronger than that in the DyCl(3) in PVA which is further confirmed by lifetime
      studies with different concentrations of Dysprosium ion (Dy(3+)). The generation
      of white light with chromaticity coordinates (0.30, 0.34) makes it potential
      material for white LED and display devices.

PMID- 21947609
TI  - Intrinsic and extrinsic temperature-dependency of viscosity-sensitive fluorescent
      molecular rotors.
AB  - Molecular rotors are a group of environment-sensitive fluorescent probes whose
      quantum yield depends on the ability to form twisted intramolecular charge
      transfer (TICT) states. TICT formation is dominantly governed by the solvent's
      microviscosity, but polarity and the ability of the solvent to form hydrogen
      bonds play an additional role. The relationship between quantum yield phi(F) and
      viscosity eta is widely accepted as a power-law, phi(F) = C . eta(x). In this
      study, we isolated the direct influence of the temperature on the TICT formation
      rate by examining several molecular rotors in protic and aprotic solvents over a
      range of temperatures. Each solvent's viscosity was determined as a function of
      temperature and used in the above power-law to determine how the proportionality
      constant C varies with temperature. We found that the power-law relationship
      fully explains the variations of the measured steady-state intensity by
      temperature-induced variations of the solvent viscosity, and C can be assumed to
      be temperature-independent. The exponent x, however, was found to be
      significantly higher in aprotic solvents than in protic solvents. We conclude
      that the ability of the solvent to form hydrogen bonds has a major influence on
      the relationship between viscosity and quantum yield. To use molecular rotors for
      the quantitative determination of viscosity or microviscosity, the exponent x
      needs to be determined for each dye-solvent combination.

PMID- 21947611
TI  - Analysis of lanthanide-induced conformational change of the C-terminal domain on
      centrin.
AB  - Centrin, an EF-hand calcium-binding protein with high homology to calmodulin
      (CaM), is an essential component of microtubule-organizing center (MTOC).
      Lanthanide (Ln) ions can improve the stability, increase the amount and enhance
      the orderliness of microtubules, which are components of cytoskeleton. In order
      to investigate the structural basis of Ln ions on enhancing orderliness of
      microtubules, we characterized the binding properties of Ln ions with the
      isolated C-terminal domain of the Euplotes centrin (C-EoCen). Results suggested
      that Ln ions may occupy the canonical Ca(2+) binding sites on C-EoCen with middle
      affinity. Near- and far-UV CD spectra of C-EoCen displayed pronounced differences
      before and after additing Ln ions. The asymmetry of microenvironments of Phe on C
      EoCen was changed. Using 2-p-toluidinylnaphthalene-6- sulfonate (TNS) as probe,
      Ln ions induced C-EoCen to undergo conformational changes from closed state to
      open state, resulting in exposing hydrophobic patches to external environments.
      Ln ions have more obvious effect on the conformation of centrin than Ca(2+). The
      differences found in the interactions of centrin binding with Ln ions/Ca(2+)
      maybe provide some insights for structural basis of centrin functions in vivo.

PMID- 21947612
TI  - Binding of engeletin with bovine serum albumin: insights from spectroscopic
      investigations.
AB  - In this paper, several spectroscopic techniques were used to investigate the
      interaction of engeletin (ELN) with bovine serum albumin (BSA). The analysis of
      UV-Vis absorption and fluorescence spectra revealed that ELN and BSA formed a
      static complex ELN-BSA, and ELN quenched the fluorescence of BSA effectively.
      According to the thermodynamic parameters DeltaS(0) = 47.27 J.mol(-1).K(-1) and
      DeltaEta(0) = -10.34 kJ.mol(-1), the hydrophobic and hydrogen bond interactions
      were suggested to be the major interaction forces between ELN and BSA. Raman
      spectroscopy indicated that the binding of ELN slightly changed the conformations
      and microenviroment of BSA and decreased the alpha-helix content of BSA.

PMID- 21947613
TI  - Optical, structural and thermodynamic studies of the association of an anti
      leucamic drug imatinib mesylate with transport protein.
AB  - The interaction of an anti-leukemic drug, imatinib mesylate (IMT) with human
      serum albumin (HSA) was investigated by fluorescence, synchronous fluorescence,
      three-dimensional fluorescence, circular dichroism and UV-vis absorption
      techniques under physiological condition. The process of binding of IMT on HSA
      was observed to be through a spontaneous molecular interaction procedure. IMT
      effectively quenched the intrinsic fluorescence of HSA via static quenching. The
      values of binding constant, number of molecules that interact simultaneously with
      the binding site and thermodynamic parameters were evaluated by carrying out the
      interactions at three different temperatures. Based on thermodynamic parameters
      and displacement studies with site probes, it was proposed that the drug bound at
      Sudlow's site I of subdomain IIA. The change in the conformation of HSA was
      evident from synchronous, three-dimensional fluorescence and circular dichroism
      studies. The distance between the donor (protein) and acceptor (drug) was
      calculated based on the Foster's theory of resonance energy stransfer and it was
      found to be 1.30 nm. The effect of different metal ions on the binding of the
      drug to protein was also investigated.

PMID- 21947614
TI  - Serotonin and molecular neuroimaging in humans using PET.
AB  - The serotonergic system is one of the most important modulatory neurotransmitter
      systems in the human brain. It plays a central role in major physiological
      processes and is implicated in a number of psychiatric disorders. Along with the
      dopaminergic system, it is also one of the phylogenetically oldest human
      neurotransmitter systems and one of the most diverse, with 14 different receptors
      identified up to this day, many of whose function remains to be understood. The
      system's functioning is even more diverse than the number of its receptors, since
      each is implicated in a number of different processes. This review aims at
      illustrating the distribution and summarizing the main functions of the serotonin
      (5-hydroxytryptamin, 5-HT) receptors as well as the serotonin transporter (SERT,
      5-HTT), the vesicular monoamine transporter 2, monoamine oxidase type A and 5-HT
      synthesis in the human brain. Recent advances in in vivo quantification of these
      different receptors and enzymes that are part of the serotonergic system using
      positron emission tomography are described.

PMID- 21947615
TI  - Accumulation and effects of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine
      (HMX) exposure in the green anole (Anolis carolinensis).
AB  - Environmental contamination by energetic compounds is an increasing international
      concern, although little is known of their accumulation in and affect on
      wildlife. Reptiles are often good models for contaminants studies due to natural
      history traits that increase their potential for exposure. We report a study to
      assess accumulation and effects of octahydro-1,3,5,7-tetranitro-1,3,5,7
      tetrazocine (HMX, High Melting Explosive) in green anoles (Anolis carolinensis).
      Acute oral toxicity (LD(50)) was estimated to exceed 2000 mg/kg body weight in
      adult male and female anoles using a standard up-and-down method. Accumulation of
      HMX was assessed in adult females via dietary exposure and into eggs by two
      routes (directly from the soil and via maternal transfer). HMX readily
      accumulated into adult females in a dose-dependent manner and into eggs following
      both exposure pathways. However, total HMX in soil-exposed eggs was up to 40
      times greater than those exposed via maternal transfer. Although there was a
      suggestion of an HMX-induced reduction in body weight in adult females, overall
      there were no effects observed over the 12 week exposure period. The only
      significant effect on eggs was a 50% reduction in hatching success for eggs
      exposed to 2000 mg/kg HMX in the soil during incubation. Growth and survival of
      hatchlings was not affected by HMX exposure. Our results demonstrate that HMX
      accumulates through the food chain and into eggs from the soil, but likely poses
      minimal threat to lizards except to hatching success in eggs incubated in soils
      with HMX levels near maximum environmental concentrations.

PMID- 21947616
TI  - The effects of parental depressive symptoms, appraisals, and physical punishment
      on later child externalizing behavior.
AB  - Examined a cognitive-behavioral pathway by which depressive symptoms in mothers
      and fathers increase risk for later child externalizing problem behavior via
      parents' appraisals of child behavior and physical discipline. Participants were
      245 children (118 girls) at risk for school-age conduct problems, and their
      parents and teachers. Children were approximately 3 years old at Time 1 (T1) and
      5 1/2 years old at Time 2 (T2). At T1, mothers and fathers reported their
      depressive symptoms, perceptions of their child's reciprocal affection and
      responsiveness, frequency of physical punishment, and child externalizing
      problems. Mothers, fathers, and teachers provided ratings of externalizing
      behavior at T2. Structural equation modeling revealed that parents' negative
      attributions mediated positive relations between their depressive symptoms and
      frequency of physical punishment for both fathers and mothers. More frequent
      physical punishment, in turn, predicted increased child externalizing behavior at
      T2. In future research, transactional mechanisms underlying effects of clinical
      depression on child conduct problems should be explored at multiple stages of
      development. For parents showing depressive symptoms, restructuring distorted
      perceptions about their children's behavior may be an important component of
      intervention programs.

PMID- 21947617
TI  - Disorganized attachment and inhibitory capacity: predicting externalizing problem
      behaviors.
AB  - The aim of the present study was to investigate whether attachment insecurity,
      focusing on disorganized attachment, and the executive function (EF) component of
      inhibition, assessed at age 5, were longitudinally related to general
      externalizing problem behaviors as well as to specific symptoms of ADHD and
      Autism spectrum disorder (ASD), and callous-unemotional (CU) traits. General
      externalizing problem behaviors were also measured at age 5 to allow for a
      developmental analysis. Outcome variables were rated by parents and teachers. The
      sample consisted of 65 children with an oversampling of children with high levels
      of externalizing behaviors. Attachment was evaluated using a story stem
      attachment doll play procedure. Inhibition was measured using four different
      tasks. The results showed that both disorganized attachment and poor inhibition
      were longitudinally related to all outcome variables. Controlling for initial
      level of externalizing problem behavior, poor inhibition predicted ADHD symptoms
      and externalizing problem behaviors, independent of disorganized attachment,
      whereas for ASD symptoms no predictive relations remained. Disorganized
      attachment independently predicted CU traits.

PMID- 21947618
TI  - The effects of childhood ADHD symptoms on early-onset substance use: a Swedish
      twin study.
AB  - Research has documented that children and adolescents with attention
      deficit/hyperactivity disorder (ADHD) are at increased risk of substance use
      problems. Few studies, however, have focused on early-onset substance use. This
      study therefore investigated how the two symptom dimensions of ADHD
      (hyperactivity/impulsivity and inattention) are associated with early-onset
      substance use, the role of persistent ADHD for the association, and to what
      extent the association is influenced by genetic and environmental factors. Twins
      (1,480 pairs) in the Swedish Twin Study of Child and Adolescent Development were
      followed from childhood to adolescence. ADHD symptoms were measured at age 8-9
      and age 13-14 via parent-report, whereas substance use was assessed at age 13-14
      via self-report. Results revealed that hyperactive/impulsive symptoms predicted
      early-onset "sometimes" tobacco use (adjusted odds ratios, 1.12, for one symptom
      count), controlling for inattentive symptoms and conduct problem behaviors. There
      is no independent effect of inattentive symptoms on early-onset substance use.
      Children with persistent hyperactivity/impulsivity (defined as scoring above the
      75th percentile at both time points) had a pronounced risk of both early-onset
      tobacco and alcohol use (adjusted odds ratios from 1.86 to 3.35, compared to the
      reference group). The associations between hyperactivity/impulsivity and early
      onset substance use were primarily influenced by genetic factors. Our results
      indicated that hyperactivity/impulsivity, but not inattention, is an important
      early predictor for early-onset substance use, and a shared genetic
      susceptibility is suggested to explain this association.

PMID- 21947619
TI  - Functional analysis of light-regulated promoter region of AtPollambda gene.
AB  - Genetic and molecular analyses mainly in Arabidopsis and in some other plants
      have demonstrated involvement of light signaling in cell cycle regulation. In
      this report, we show light-mediated activation of the promoter of AtPollambda
      gene, a homolog of mammalian DNA polymerase lambda in Arabidopsis thaliana and an
      important component of DNA damage repair/recombination machinery in plants.
      Analyses of the light-mediated promoter activity using various deletion versions
      of AtPollambda promoter in transformed Arabidopsis and tobacco (Nicotiana
      tabaccum) plants indicate that a 130-bp promoter region between -536 and -408 of
      AtPollambda promoter is essential for light-induced regulation of AtPollambda
      expression. DNA-protein interaction studies reveal that an ATCT-motif and AE-box
      light-responsive elements in the light-regulated promoter region confer light
      responsiveness of AtPollambda promoter. DNA-binding analysis has identified a 63
      kDa trans-acting protein factor which showed specific binding to ATCT-motif,
      while another trans-acting factor of ~52 kDa was found to bind specifically to
      both ATCT and AE-box sequences. The 52-kDa protein has been identified as B3
      domain transcription factor by MALDI-TOF/MS analysis. Overall, our results
      provide novel information on the role of light signaling in regulation of
      expression of an important component of DNA repair machinery in plants.

PMID- 21947621
TI  - Genetic variation in strigolactone production and tillering in rice and its
      effect on Striga hermonthica infection.
AB  - Tillering in cereals is a complex process in the regulation of which also signals
      from the roots in the form of strigolactones play an important role. The
      strigolactones are signalling molecules that are secreted into the rhizosphere
      where they act as germination stimulants for root parasitic plants and hyphal
      branching factors for arbuscular mycorrhizal fungi. On the other hand, they are
      also transported from the roots to the shoot where they inhibit tillering or
      branching. In the present study, the genetic variation in strigolactone
      production and tillering phenotype was studied in twenty rice varieties collected
      from all over the world and correlated with S. hermonthica infection. Rice
      cultivars like IAC 165, IAC 1246, Gangweondo and Kinko produced high amounts of
      the strigolactones orobanchol, 2'-epi-5-deoxystrigol and three methoxy-5
      deoxystrigol isomers and displayed low amounts of tillers. These varieties
      induced high S. hermonthica germination, attachment, emergence as well as dry
      biomass. In contrast, rice cultivars such as Super Basmati, TN 1, Anakila and
      Agee displayed high tillering in combination with low production of the
      aforementioned strigolactones. These varieties induced only low S. hermonthica
      germination, attachment, emergence and dry biomass. Statistical analysis across
      all the varieties confirmed a positive correlation between strigolactone
      production and S. hermonthica infection and a negative relationship with
      tillering. These results show that genetic variation in tillering capacity is the
      result of genetic variation in strigolactone production and hence could be a
      helpful tool in selecting rice cultivars that are less susceptible to S.
      hermonthica infection.

PMID- 21947622
TI  - Translaminar screw fixation of the cervical spine in Asian population:
      feasibility and safety consideration based on computerized tomographic
      measurements.
AB  - PURPOSE: Cervical translaminar screw fixation has been shown to be safe,
      efficient and provides alternative for cervical fixation. However, its use in the
      Asian population should be considered cautiously because the cervical lamina
      diameter may not be adequate to accommodate the standard lamina screw size. We
      studied the average transverse lamina diameter of the cervical spine in the
      Malaysian population to evaluate the feasibility and safety of lamina screw
      fixation in this population. METHODS: The measurements of the cervical lamina
      were performed on CT images. The diameters were defined as the most inner or
      outer diameter of the lamina, taken perpendicular to the axis of the lamina and
      measured in millimeters up to 0.1 mm. RESULTS: The mean transverse inner diameter
      of the lamina of C2, C3, C4, C5, C6 and C7 was 3.4, 2.0, 1.7, 1.9, 2.3 and 3.4
      mm, respectively. The lamina of C2 and C7 has the largest transverse inner
      diameter and the lamina of C4 the smallest. The mean transverse outer diameter of
      the lamina of C2, C3, C4, C5, C6 and C7 was 5.6, 3.5, 3.1, 3.1, 3.9 and 5.8 mm,
      respectively. The lamina of C7 has the largest transverse outer diameter and the
      lamina of C4 and C5 the smallest. CONCLUSIONS: Translaminar fixation using a 3.5
      screw should be attempted with caution in Asian population. Pre-operative CT scan
      evaluation is mandatory before translaminar screw fixation is attempted.

PMID- 21947620
TI  - Features of a unique intronless cluster of class I small heat shock protein genes
      in tandem with box C/D snoRNA genes on chromosome 6 in tomato (Solanum
      lycopersicum).
AB  - Physical clustering of genes has been shown in plants; however, little is known
      about gene clusters that have different functions, particularly those expressed
      in the tomato fruit. A class I 17.6 small heat shock protein (Sl17.6 shsp) gene
      was cloned and used as a probe to screen a tomato (Solanum lycopersicum) genomic
      library. An 8.3-kb genomic fragment was isolated and its DNA sequence determined.
      Analysis of the genomic fragment identified intronless open reading frames of
      three class I shsp genes (Sl17.6, Sl20.0, and Sl20.1), the Sl17.6 gene flanked by
      Sl20.1 and Sl20.0, with complete 5' and 3' UTRs. Upstream of the Sl20.0 shsp, and
      within the shsp gene cluster, resides a box C/D snoRNA cluster made of SlsnoR12.1
      and SlU24a. Characteristic C and D, and C' and D', boxes are conserved in
      SlsnoR12.1 and SlU24a while the upstream flanking region of SlsnoR12.1 carries
      TATA box 1, homol-E and homol-D box-like cis sequences, TM6 promoter, and an
      uncharacterized tomato EST. Molecular phylogenetic analysis revealed that this
      particular arrangement of shsps is conserved in tomato genome but is distinct
      from other species. The intronless genomic sequence is decorated with cis
      elements previously shown to be responsive to cues from plant hormones,
      dehydration, cold, heat, and MYC/MYB and WRKY71 transcription factors.
      Chromosomal mapping localized the tomato genomic sequence on the short arm of
      chromosome 6 in the introgression line (IL) 6-3. Quantitative polymerase chain
      reaction analysis of gene cluster members revealed differential expression during
      ripening of tomato fruit, and relatively different abundances in other plant
      parts.

PMID- 21947624
TI  - Cellulosic ethanol production on temperature-shift simultaneous saccharification
      and fermentation using the thermostable yeast Kluyveromyces marxianus CHY1612.
AB  - In cellulosic ethanol production, use of simultaneous saccharification and
      fermentation (SSF) has been suggested as the favorable strategy to reduce process
      costs. Although SSF has many advantages, a significant discrepancy still exists
      between the appropriate temperature for saccharification (45-50  degrees C) and
      fermentation (30-35  degrees C). In the present study, the potential of
      temperature-shift as a tool for SSF optimization for bioethanol production from
      cellulosic biomass was examined. Cellulosic ethanol production of the temperature
      shift SSF (TS-SSF) from 16 w/v% biomass increased from 22.2 g/L to 34.3 g/L
      following a temperature shift from 45 to 35  degrees C compared with the constant
      temperature of 45  degrees C. The glucose conversion yield and ethanol production
      yield in the TS-SSF were 89.3% and 90.6%, respectively. At higher biomass loading
      (18 w/v%), ethanol production increased to 40.2 g/L with temperature-shift time
      within 24 h. These results demonstrated that the temperature-shift process
      enhances the saccharification ratio and the ethanol production yield in SSF, and
      the temperature-shift time for TS-SSF process can be changed according to the
      fermentation condition within 24 h.

PMID- 21947623
TI  - The anatomic relationship around the horizontal segment of petrous internal
      carotid artery: a study based on reconstructed computed tomography angiography.
AB  - PURPOSE: The anatomic relationship around the horizontal segment of petrous
      internal carotid artery (ICA) is complicated. Relative researches on human
      patients using radiographic technique are scarce. It is essential to get adequate
      anatomic knowledge about this region for performing some bypass procedures.
      METHODS: Using the independent software Mimics, we prospectively studied the 0.45
      mm-thick computed tomography angiography (CTA) images of 29 patients (58 sides).
      All patients' middle cranial fossa and related critical anatomic structures were
      reconstructed in 3D. Some measurements were established on the multiplanar
      reconstructed images, including the distance from foramen ovale and foramen
      spinosum to the petrous ICA; the distance from the lumen of cochlea to the edge
      of trigeminal impression and petrous ICA; and the length of the horizontal
      segment of petrous ICA. RESULTS: The horizontal segment of petrous ICA was
      surrounded by the trigeminal impression, the cochlea and the auditory tube
      spatially. On the multiplanar reconstructed CTA images, the average distances
      from foramen ovale and foramen spinosum to the petrous ICA were 4.1 mm and 5.8
      mm, respectively; the average distance from the lumen of cochlea to the edge of
      trigeminal impression and petrous ICA were 8.2 mm and 2.0 mm, respectively; and
      the mean length of the horizontal segment of petrous ICA was 15.8 mm.
      CONCLUSIONS: Our results indicate adequate and reliable anatomic information can
      be obtained using reconstructed CTA on an individualized basis.

PMID- 21947625
TI  - Enhanced biological nitrogen removal in MLE combined with post-denitrification
      process and EF clarifier.
AB  - A modified ludzack ettinger reactor (MLE) combined with a post-denitrification
      reactor (PDMLE) using electroflotation (EF) as a secondary clarifier was
      investigated on its feasibility and process performance. Results indicated that
      higher mixed liquor suspended solids (MLSS) concentrations in bioreactor (5,350
      +/- 352 mg L(-1)) were maintained via the highly concentrated return sludge
      (16,771 +/- 991 mg L(-1)) from the EF clarifier and the effluent suspended solids
      (SS) concentrations continued relatively low, representing effluent SS
      concentration of 1.71 +/- 1.16 mg L(-1), compared with GS-A2O process during the
      operation of four months. The denitrification was improved by combining MLE
      process with post-denitrification based on endogenous decay (i.e. no additional
      carbon source was added), resulting in the removal efficiencies of TN were about
      91 and 59% for the influent C/N ratio of 10 and 5, respectively, revealing
      relatively high nitrogen removal as compared with EF-A2O and gravity settling
      (GS)-A2O processes as a control. The nitrogen balance analysis indicates that pre
      denitrification and post-denitrification contributed to 78 and 22% of TN removed,
      respectively.

PMID- 21947626
TI  - Percutaneous coronary intervention versus bypass surgery for left main coronary
      artery disease: a meta-analysis of randomised trials.
AB  - AIMS: We performed a meta-analysis of randomised trials comparing percutaneous
      coronary intervention (PCI) with stent implantation to coronary artery bypass
      grafting (CABG) for the treatment of unprotected left main coronary artery
      stenosis (ULMCA). METHODS AND RESULTS: Pubmed and other databases were searched.
      Data were expressed as odds ratios (OR) with 95% confidence interval (CI). Four
      randomised trials enrolling 1,611 patients were selected. At 12-month follow-up
      PCI, as compared to CABG, was associated with a significant risk reduction of
      stroke (0.12% vs. 1.90%, OR 0.14, 95% CI [0.04 to 0.55], p=0.004), with an
      increased risk of repeat revascularisation (11.03% vs. 5.45%, OR 2.17, 95% CI
      [1.48 to 3.17], p <0.001), a similar risk of mortality (OR 0.72, 95% CI [0.42 to
      1.24], p=0.23) or myocardial infarction (OR 0.97, 95% CI [0.54 to 1.74], p=0.91),
      leading to an increased risk of major adverse cardiovascular events (14.37% vs.
      10.14%, OR 1.50, 95% CI [1.10 to 2.04], p=0.01) and similar hazard of major
      adverse cardiac or cerebrovascular events (14.49% vs. 12.04%, OR 1.24, 95% CI
      [0.93 to 1.67], p=0.15). CONCLUSIONS: PCI is comparable to CABG for the treatment
      of ULMCA with respect to the composite of major adverse cardiovascular or
      cerebrovascular events at 12-month follow-up.

PMID- 21947627
TI  - Chemotherapy between the first and second stages of a two-stage hepatectomy for
      colorectal liver metastases: should we routinely recommend it?
AB  - BACKGROUND: The aim of the present study is to examine the effect of systemic
      chemotherapy after the 1st-stage hepatectomy (CT*2) on the progression of disease
      and dropout rates. A major pitfall of the 2-stage hepatectomy procedure is a high
      dropout rate after the 1st-stage hepatectomy due to progression of disease (PD).
      Routine use of CT*2 has been advocated. METHODS: A total of 47 patients with
      multiple, bilateral unresectable liver metastases were selected for a 2-stage
      hepatectomy procedure (+/-portal vein occlusion). RESULTS: Of the total, 37
      patients (78.7%) underwent systemic chemotherapy before the 1st-stage hepatectomy
      (CT*1) and 25 patients (53.2%) underwent CT*2; PD was significantly more common
      during CT*2 than during CT*1 (P=.002). Of the 47 patients planned for the 2nd
      stage hepatectomy, 36 (76.6%) completed the procedure. Of these 47 patients, 25
      (53.2%) showed PD after the 1st-stage hepatectomy, 12 in the CT*2 group and 13 in
      the no-CT*2 group; administration of CT*2 did not significantly affect the PD
      rate (P=.561). The overall dropout rate was 23.4% (n=11 patients): 16% in the
      CT*2 group vs. 31.8% in the no-CT*2 group (P=.303). CONCLUSIONS: The routine use
      of chemotherapy between the 1st- and 2nd-stage hepatectomy does not guarantee
      lower PD and dropout rates.

PMID- 21947629
TI  - Effects of additional blood pressure and lipid measurements on the prediction of
      cardiovascular risk.
AB  - BACKGROUND: Current guidelines recommend that decisions to start preventative
      therapy for cardiovascular disease (CVD) should be based on absolute risk;
      however, current risk equations are based on single measurements of risk factors.
      We aimed to assess whether two measurements of blood pressure and lipids improves
      the prediction of cardiovascular risk compared to one measurement. METHODS AND
      RESULTS: We used sex-specific Cox proportional hazards models to evaluate the
      risk of first CVD event in 2385 participants of the Framingham Offspring Study
      attending both the second and third visits. We estimated the effects on risk
      prediction of using the average of two measurements of blood pressure, total
      cholesterol, and HDL cholesterol compared to using one measurement of the risk
      factors. We found that these risk factors were each markedly more predictive of
      CVD when the average of two measurements was used rather than one measurement and
      age was less predictive of CVD. There were small improvements in the overall
      model fit, discrimination, and calibration. Reclassification also showed small
      improvements across the risk spectrum (net reclassification information, NRI, for
      women 3.0%, 95% CI -0.9 to 24.8%; NRI for men 4.0%, 95% CI -2.2 to 14.1%) and
      possibly greater improvements for intermediate-risk individuals (NRI for women
      32.3%, 95% CI -21.9 to 46.8%; NRI for men 16.0%, 95% CI -3.3 to 43%).
      CONCLUSIONS: Averaging two measurements of blood pressure and lipids results in
      marked increases in the predictiveness of these risk factors and smaller
      improvements in the overall prediction of cardiovascular risk including
      reclassification.

PMID- 21947630
TI  - Twenty-year trends in cardiovascular risk factors in India and influence of
      educational status.
AB  - BACKGROUND: Urban middle-socioeconomic status (SES) subjects have high burden of
      cardiovascular risk factors in low-income countries. To determine secular trends
      in risk factors among this population and to correlate risks with educational
      status we performed epidemiological studies in India. METHODS: Five cross
      sectional studies were performed in middle-SES urban locations in Jaipur, India
      from years 1992 to 2010. Cluster sampling was performed. Subjects (men, women)
      aged 20-59 years evaluated were 712 (459, 253) in 1992-94, 558 (286, 272) in 1999
      2001, 374 (179, 195) in 2002-03, 887 (414, 473) in 2004-05, and 530 (324, 206) in
      2009-10. Data were obtained by history, anthropometry, and fasting blood glucose
      and lipids estimation. Response rates varied from 55 to 75%. Mean values and risk
      factor prevalence were determined. Secular trends were identified using quadratic
      and log-linear regression and chi-squared for trend. RESULTS: Across the studies,
      there was high prevalence of overweight, hypertension, and lipid abnormalities.
      Age- and sex-adjusted trends showed significant increases in mean body mass index
      (BMI), fasting glucose, total cholesterol, high-density lipoprotein (HDL)
      cholesterol, and triglycerides (quadratic and log-linear regression, p < 0.001).
      Systolic blood pressure (BP) decreased while insignificant changes were observed
      for waist-hip ratio and low-density lipoprotein (LDL) cholesterol. Categorical
      trends showed increase in overweight and decrease in smoking (p < 0.05);
      insignificant changes were observed in truncal obesity, hypertension,
      hypercholesterolaemia, and diabetes. Adjustment for educational status attenuated
      linear trends in BMI and total and LDL cholesterol and accentuated trends in
      systolic BP, glucose, and HDL cholesterol. There was significant association of
      an increase in education with decline in smoking and an increase in overweight
      (two-line regression p < 0.05). CONCLUSION: In Indian urban middle-SES subjects
      there is high prevalence of cardiovascular risk factors. Over a 20-year period
      BMI and overweight increased, smoking and systolic BP decreased, and truncal
      obesity, hypercholesterolaemia, and diabetes remained stable. Increasing
      educational status attenuated trends for systolic BP, glucose and HDL
      cholesterol, and BMI.

PMID- 21947632
TI  - Obesity. Editor's note.

PMID- 21947631
TI  - The incidence of asymmetrical left/right skeletal and dental development in an
      Australian population and the effect of this on forensic age estimations.
AB  - The prevalence of developmental asymmetry between left and right sides of the
      body in the third molar tooth and medial clavicular epiphysis is examined in a
      contemporary Australian population (92% Caucasian). The contention that
      differences between left and right side developmental timing is statistically
      insignificant, and can therefore be ignored in forensic age estimation
      procedures, is questioned. It was found that of a population sample of 604
      individuals, 177 displayed asymmetrical timing in development between antimeres
      of the third molar, the medial clavicle or both. There was no correlation found
      between the third molar tooth and medial clavicular epiphysis in terms of
      left/right synchronicity. For those individuals differing in development by two
      or more developmental stages in either age marker or one stage in both age
      markers, the effect upon the accuracy of forensic age estimations can be
      significant. Differences in age estimates for each side were as much as 3.1
      years. Age estimations based on one side only may not provide the best estimate
      for an individual, and more accurate results can be achieved if both sides are
      taken into consideration. A protocol for dealing with asymmetrical development is
      discussed with reference to the multifactorial age estimation method proposed by
      the same authors in previous research.

PMID- 21947633
TI  - Obesity medicine--the time has come.

PMID- 21947634
TI  - A review of evidence-based strategies to treat obesity in adults.
AB  - Obesity, with its comorbidities, is a major public health problem. Population
      based surveys estimate 2 of every 3 U.S. adults are overweight or obese. Despite
      billions of dollars spent annually on weight loss attempts, recidivism is high
      and long-term results are disappointing. In simplest terms, weight loss and
      maintenance depend on energy balance, and a combination of increased energy
      expenditure by exercise and decreased energy intake through caloric restriction
      is the mainstay of behavioral interventions. Many individuals successfully lose
      5%-10% of body weight through behavioral approaches and thereby significantly
      improve health. Similar success occurs with some weight loss prescriptions,
      although evidence for successful weight loss with over-the-counter medications
      and supplements is weak. Commercial weight loss programs have helped many
      individuals achieve their goals, although few programs have been carefully
      evaluated and compared, limiting recommendations of one program over another. For
      the very obese, bariatric surgery is an option that leads to significant weight
      loss and improved health, although risks must be carefully weighed. Lifestyle
      changes, including regular physical activity, healthy food choices, and portion
      control, must be adopted, regardless of the weight loss approach, which requires
      ongoing support. Patients can best decide the appropriate approach working with a
      multidisciplinary team, including their health care provider and experts in
      nutrition, exercise, and behavioral intervention.

PMID- 21947635
TI  - Surgical management of obesity: current state of procedure evolution and
      strategies to optimize outcomes.
AB  - Surgical treatment of morbid obesity remains the most effective modality
      available. Procedures have evolved over the past 50 years and have utilized
      caloric restriction and malabsorption, alone or in combination. Optimizing
      outcome and preserving good nutrition health is the goal of the multidisciplinary
      care that these patients need. The objective of this article is to review the
      evolution of bariatric surgery with an emphasis on the current procedures being
      performed in the United States. Recommendations for diet and vitamin/mineral
      supplementation for specific procedures are reviewed, as well as identification
      and management of some procedure-related complications.

PMID- 21947636
TI  - Endoscopic approaches for the treatment of obesity: fact or fiction?
AB  - Obesity is a common medical problem that is growing in both numbers of patients
      and cost to the healthcare system. In addition, the disabilities associated with
      obesity can have significant impact on a patient's quality of life. The
      interventions to date for treating obesity are generally divided into 2
      categories: conservative (diet, exercise, behavioral management, and
      pharmacology) and surgical. The success rate of conservative management has been
      modest, at best. Surgical therapy, which can create enduring and significant
      weight loss in some situations, has its associated morbidity, mortality, and
      cost. Surgical therapy is not appropriate for someone seeking to lose a modest
      amount of weight. Internationally, endoscopic devices for obesity are available.
      Published reports have demonstrated some success in obtaining weight loss with
      these endoscopic devices. The most common is the intragastric balloon. Other
      endoscopic obesity devices are in development. These devices may play a role in
      weight loss therapy and serve as part of the therapeutic continuum between
      conservative management and surgery that clinicians and patients can choose from
      for the treatment of obesity.

PMID- 21947637
TI  - Nutraceutical supplements for weight loss: a systematic review.
AB  - Obesity is a global public health issue. Although the etiology of this global
      epidemic is multifactorial, most sufferers would be delighted to find a
      relatively effortless way to lose weight. Herbal "weight loss pills" can fit the
      bill. The authors systematically review the scientific evidence concerning
      various weight loss agents that are available over the counter or in food stores.
      The review provides a starting point to make informed choices among nutraceutical
      agents promoted for weight loss, as well as advice for incorporating healthy
      alternatives in the diet.

PMID- 21947638
TI  - Reading, writing, and obesity: America's failing grade in school nutrition and
      physical education.
AB  - The childhood obesity epidemic has left healthcare professionals and laymen alike
      questioning the best strategy to improve children's health in the future. To
      effectively combat childhood obesity, we must have a thorough understanding of
      the establishment and development of programs currently responsible for pediatric
      health. This article explores the history of two influential programs affecting
      children's diet and physical activity levels in schools: the National School
      Lunch Program and physical education classes. It is revealed that the National
      School Lunch Program contributes to the overall school nutrition environment,
      including the presence of fast food and vending machines on campuses. The history
      of physical education is traced back to ancient Greece, and it is shown that the
      familiar sports-based curriculum is an advent of the 19th century, with the roots
      of physical education originating from the founders of preventive medicine.
      Select childhood obesity and health intervention studies are reviewed with a
      focus on identifying notable features pertaining to the effectiveness of these
      programs. Future directions and recommendations, based on the history of these
      programs as well as evidence from current pediatric health studies, outlining the
      basis for a modernized health-based physical education curriculum designed to
      address today's public health concerns, are further discussed.

PMID- 21947639
TI  - Nonalcoholic fatty liver disease: a review of the spectrum of disease, diagnosis,
      and therapy.
AB  - Worldwide, there is an epidemic of obesity and overweight, with two-thirds of
      Americans affected. A strong association exists between excessive body weight and
      nonalcoholic fatty liver disease (NAFLD), the most common etiology of abnormal
      liver function tests. Nonalcoholic fatty liver disease is a spectrum of liver
      disease, from a "bland" fatty infiltration to chronic hepatitis (nonalcoholic
      steatohepatitis or NASH), that can result in cirrhosis and organ failure. With
      the increasing prevalence of obesity in the world, the proportion of people
      affected by NAFLD is only expected to be parallel. Although primarily noted in
      obese individuals, NAFLD has also been associated with a number of surgical
      procedures, metabolic conditions, and medications. NASH is commonly
      underdiagnosed as most affected patients are symptom free, and routine screening
      is not performed. Noninvasive diagnostic testing is not sensitive in diagnosis or
      staging the severity of disease. Fatty infiltration and oxidative injury to the
      hepatocytes are believed to be the major factors behind the progression of
      disease from simple fatty infiltration of the liver to chronic hepatitis.
      Understanding the inflammatory pathways involved in NASH is a subject of
      extensive research. Currently, few proven treatment options exist, and controlled
      weight reduction is the only safe modality recommended for treatment of NASH.

PMID- 21947640
TI  - Hypocaloric home parenteral nutrition and nutrition parameters in patients
      following bariatric surgery.
AB  - BACKGROUND: Surgical intervention is considered an acceptable treatment for
      morbid obesity. Complications following bariatric surgery procedures (BSPs) may
      necessitate home parenteral nutrition (HPN). No studies have been published on
      patients receiving HPN following BSP complications. The study aim was to
      determine if hypocaloric HPN has an effect on body mass index (BMI), albumin, and
      HPN complications. METHODS: A historic cohort of patients was identified from a
      clinical database. Obese patients (BMI >=35 kg/m(2)) who underwent BSP and
      received HPN for an anastomotic leak/fistula or bowel obstruction were included.
      Comparisons for start and end of therapy were made for calorie and protein
      intake, BMI, white blood cell count, and serum albumin level. Readmissions and
      metabolic and infectious complications were recorded. Obese patients received
      hypocaloric feeds to promote weight loss and protein for wound healing. RESULTS:
      Twenty-three patients were included for an average study length of 1.5 months.
      Patients received an average of 1.2 g of protein and a median of 13.6 kcal per kg
      actual body weight (ABW) per day. BMI decreased by 7.1% +/- 5.2%, from a median
      of 39.8 to 37.1, and serum albumin increased by 12.5%, from 2.8 +/- 0.5 to 3.2 +/
      0.6 g/dL. Readmissions occurred in 52.2% of patients with 40.0% of complications
      related to HPN. CONCLUSIONS: Hypocaloric HPN is efficacious in maintaining
      adequate nutrition while allowing for weight loss in morbidly obese patients
      following complications of bariatric surgery. Frequency of HPN complications was
      comparable to those reported in the literature.

PMID- 21947641
TI  - Neurologic dysfunction and pancytopenia secondary to acquired copper deficiency
      following duodenal switch: case report and review of the literature.
AB  - The duodenal switch (DS) procedure is a type of restrictive-malabsorptive
      bariatric surgery that is typically reserved for severe morbidly obese people
      (body mass index >50 kg/m(2)) with obesity-related comorbidities, when diet,
      lifestyle changes, and pharmacologic therapy fail to achieve adequate weight
      loss. Patients who undergo the DS procedure are at risk for malabsorption,
      malnutrition, and nutrient deficiencies. Copper deficiency is a commonly reported
      long-term complication of Roux-en-Y gastric bypass (RYGB) surgery. However, data
      are limited on copper deficiency-associated complications and their treatment in
      DS patients. This article presents a case of a patient who developed hypocupremia
      with associated pancytopenia, myeloneuropathy, and leukoencephalopathy following
      DS and reviews the literature related to the pathophysiology of copper deficiency
      and copper replacement in bariatric surgery patients. When severe diarrhea was
      present, intravenous elemental copper 4 mg (as cupric chloride)/d in addition to
      daily oral copper gluconate was necessary to correct the hypocupremia and improve
      the hematologic indices and neurologic symptoms of copper deficiency. When
      diarrhea subsided, oral elemental copper 4 mg (as copper gluconate) 3 times daily
      maintained normal serum copper concentrations and avoided the relapse of severe
      neurologic dysfunction. Regular monitoring of serum copper and ceruloplasmin
      concentrations is recommended following DS surgery to detect any copper
      deficiency before irreversible neurologic damage occurs. Long-term copper
      supplementation is likely necessary to maintain normal copper status in DS
      patients.

PMID- 21947642
TI  - The effect of low body mass index on outcome in critically ill surgical patients.
AB  - BACKGROUND: Body mass index (BMI) has been correlated with complications and
      outcome in surgical patients at the two extremes of the nutrition spectrum.
      OBJECTIVE: To study the relationship between BMI, outcome, hospital length of
      stay, and complications in patients admitted to the surgical intensive care unit
      (SICU). DESIGN: Review of prospectively acquired data in SICU patients. Data
      acquired included weight, height, age, gender, Acute Physiology and Chronic
      Health Evaluation (APACHE) II-III scores, Simplified Acute Physiology II (SAPS
      II) scores, and morbidity and mortality. Patients who stayed in the unit <24
      hours were excluded. RESULTS: Of 793 patients, 706 had a normal BMI (NBMI; mean
      22.12 kg/m2) and 87 were underweight (UBMI; mean 16.81 kg/m2). There was no
      statistically significant difference in APACHE II-III and SAPS scores. The NBMI
      group had more infections, and the UBMI group had more pulmonary complications
      (chi(2), P < .0087). There was no significant difference in acute respiratory
      distress syndrome, atrial fibrillation, myocardial infarction, septicemia, or
      ventilator- associated pneumonia (Fisher exact test, P = 0.38; chi(2), P = .41).
      The ICU length of stay between the 2 groups was not significantly different (6.7
      vs 5.8 days; P = .64). Overall, there was 11.1% (88/793) SICU mortality; 74 of
      706 (10.5%) patients expired in the NBMI group, and 14 of 87 (16.1%) patients
      expired in the UBMI group. CONCLUSIONS: Low BMI is associated with increased
      mortality in SICU patients. A BMI <18.5 kg/m2 is an independent factor affecting
      outcome in surgical critical care patients.

PMID- 21947643
TI  - Mediterranean diet and metabolic syndrome in an urban population: the Athens
      Study.
AB  - BACKGROUND: Previous studies demonstrated the beneficial impact of the
      Mediterranean diet (MedDiet) on metabolic syndrome (MetS). The aim of this study
      was to retrospectively investigate the association between MedDiet and MetS in a
      representative sample of the Athenian population in the early 1980s, when MetS
      had not been established as an entity yet. METHODS: In a cross-sectional
      epidemiologic survey of cardiovascular disease (CVD), 2,074 randomly selected
      adults were examined: 900 men and 1,174 women (age, 46.9 +/- 14.9 years). MetS
      was defined according to criteria of the National Cholesterol Education Program
      Adult Treatment Panel III. A validated questionnaire concerning nutrition habits
      was administered, and MedDiet was assessed according to guidelines of the
      Division of Nutrition/Epidemiology, Athens University Medical School. RESULTS:
      Overall, 1,023 participants (49.3%) followed MedDiet (47.3% men, 52.0% women, P =
      .033) with similar rates across age groups (P = .337). MetS was diagnosed in
      24.0% of those following MedDiet, compared with 27.9% of those not following it
      (P = .041). Participants with CVD or diabetes mellitus were less likely to follow
      MedDiet (43% vs 50%, P = .009). Multivariate analysis revealed that MedDiet is
      associated with a 20% reduction in MetS (odds ratio = 0.80, 95% confidence
      interval = 0.65-0.98), after adjustment for age, gender, smoking, light physical
      activity, serum levels of low-density lipoprotein cholesterol and gamma-glutamyl
      transferase, diabetes mellitus, CVD, family history of hypertension, and/or
      hyperlipidemia. CONCLUSIONS: Results indicate that adherence to MedDiet may
      attenuate the prevalence of MetS and, consequently, the increasing burden of
      diabetes mellitus and CVD, especially in urban populations.

PMID- 21947644
TI  - Could the level of serum albumin be a method for assessing malnutrition in
      hemodialysis patients?
AB  - BACKGROUND: Traditionally, serum albumin concentration has been used for
      assessing the nutrition status of hemodialysis patients despite evidence that the
      level is also affected by inflammation and many other underlying disorders
      frequently present in these individuals. The authors evaluated albumin as a
      nutrition parameter, comparing it with more specific anthropometric parameters.
      METHODS: The study included a cohort of 271 patients. The analysis involved data
      obtained after patients entered the study (1994-2004). Anthropometric
      measurements included skinfolds, mid-arm circumference, mid-arm muscle
      circumference, percentage of body fat, body mass index, body height, and dry
      weight. Kt/V and normalized protein catabolic rate were also determined and
      laboratory analyses undertaken. RESULTS: Serum albumin was only weakly correlated
      with mid-arm circumference (r = 0.12), mid-arm muscle circumference (r = 0.15),
      and fat-free mass (r = 0.12). Common factor analysis of nutrition parameters
      uncovered latent variables, but serum albumin was not associated strongly with
      them. The sensitivity of albumin in detecting malnutrition was 24%, with a
      specificity of 88% and a predictive value of 74%. Graphic analysis showed
      disagreement in albumin levels with percentage of body fat and mid-arm muscle
      circumference. CONCLUSION: Serum albumin determination was shown to be a test
      with low sensitivity and specificity for evaluating malnutrition in hemodialysis
      patients. The values correlated weakly and showed graphic disagreement with
      anthropometric parameters. Therefore, methods that measure percentage of body fat
      and muscle mass should be used together or instead of serum albumin level for
      assessing the nutrition status of hemodialysis patients.

PMID- 21947646
TI  - Benefits of dietary fiber in clinical nutrition.
AB  - Dietary fiber is widely recognized as an important part of a healthy diet and is
      a common addition to enteral nutrition (EN) formulas. Fiber sources differ in
      characteristics such as solubility, fermentability, and viscosity, and it is now
      well known that different types of fiber exert varying physiological effects in
      the body. Clinical studies suggest fiber can exert a wide range of benefits in
      areas such as bowel function, gut health, immunity, blood glucose control, and
      serum lipid levels. Although early clinical nutrition products contained fiber
      from a single source, it is now thought that blends of fiber from multiple
      sources more closely resemble a regular diet and may provide a greater range of
      benefits for the patient. Current recommendations support the use of dietary
      fiber in clinical nutrition when no contraindications exist, but little
      information exists about which types and combinations of fibers provide the
      relevant benefit in certain patient populations. This article summarizes the
      different types of fiber commonly added to EN products and reviews the current
      literature on the use of fiber blends in clinical nutrition.

PMID- 21947645
TI  - Implementation, process, and outcomes of nutrition best practices for infants
      <1500 g.
AB  - BACKGROUND: Extrauterine growth restriction (EUGR; weight <=10th percentile)
      affects many infants <=1500 g birth weight (BW). EUGR is associated with poor
      neurodevelopmental outcomes. The objective of this study was to evaluate the
      impact of optimizing nutrition administration in infants <=1500 g. METHODS: A
      retrospective chart review compared infants <=1500 g before (n = 32) and after (n
      = 49) implementation of nutrition practice changes designed to decrease EUGR.
      Changes included early aggressive parenteral nutrition (PN), early enteral
      feedings, trophic feedings, continuous feeding administration, protein
      fortification of 24-cal/oz mother's own breast milk, and development of a
      "feeding intolerance" algorithm. The authors evaluated demographics, growth
      parameters, secondary feeding, and discharge outcomes. Differences in subgroups
      of infants <=1000 g and 1000-1500 g BW were assessed. RESULTS: Implementation of
      the nutrition practice changes decreased EUGR as defined by weight <=10th
      percentile at discharge from 57% in the preimplementation group to 28% in the
      postimplementation group (P = .01). Weight percentile ranking at 36 weeks'
      gestational age increased significantly in infants 1001-1500 g, from the 13th to
      the 27th percentile (P = .004 and P = .01, respectively). Chronic lung disease
      decreased significantly (P = .02). There was no increase in necrotizing
      enterocolitis (6% pre vs 3% post) or in blood urea nitrogen. Days of PN and
      central line use were decreased (P = .02 and P = .07, respectively). CONCLUSIONS:
      Clearly defined changes in nutrition for infants <=1500 g significantly improved
      growth outcomes without increasing undesired outcomes.

PMID- 21947647
TI  - Vitamin E for nonalcoholic fatty liver disease.

PMID- 21947648
TI  - A thermostable recombinant transaldolase with high activity over a broad pH
      range.
AB  - Thermophilic enzymes are in high demand for various applications due to their
      prolonged lifetimes and high reaction rates at elevated temperatures. In this
      work, an open reading frame TM0295, which encodes a putative transaldolase (TAL)
      from a hyper-thermophilic microorganism, Thermotoga maritima, was cloned and
      expressed in Escherichia coli. The enzyme activity of transaldolase at high
      temperatures (e.g., at 80  degrees C) was reported here for the first time. The
      recombinant T. maritima transaldolase was extremely thermostable, with a half
      life time of 198 and 13.0 h at 60  degrees C and 80  degrees C, respectively. The
      estimated total turn-over number was 1.5 * 10(6) mol of product per mol of enzyme
      at 80  degrees C. This enzyme also exhibited high activities within a broad pH
      range of 6.0-9.0. This ultra-thermostable TAL with high activity shows great
      potential for use in such applications as the production of enzymatic biofuels
      production and the synthesis of high-value carbohydrates by cell-free synthetic
      pathway biotransformation.

PMID- 21947650
TI  - Surgical removal of infected pacemaker leads without cardiopulmonary bypass after
      failed extraction using the Excimer Laser Sheath Extraction System.
AB  - With the growing number of cardiac pacemakers and internal cardioverter
      defibrillator implantations, problems with endocardial lead infection have been
      increasing. The newly developed Excimer Laser Sheath Lead Extraction System has
      been recognized as being highly useful for removing chronic infected leads.
      However, serious bleeding complications are a concern when this system is used.
      Here we report our experience with a 67-year-old man who was diagnosed with
      pacemaker endocarditis. Initially, lead removal was attempted using the Excimer
      Laser Sheath Extraction System, though this was abandoned because of severe
      adhesion of the leads and the junction of the supra vena cava (SVC) with the
      right atrium. Surgical removal of the leads was performed without using
      cardiopulmonary bypass and the leads were removed without any complications.
      During surgery, we found there was a silent perforation of the innominate vein
      brought about by the Excimer Laser Sheath System. Also, the junction of the SVC
      with the right atrium was thought to be an area potentially at high risk of
      perforation, because of a lack of surrounding tissue. It is our opinion that
      those who carry out procedures with the Excimer Laser Sheath System should
      understand the potential risk of perforation based on cardiac anatomy and should
      be prepared for lethal bleeding complications. Also, for emergent situations, we
      believe that close backup by a cardiovascular surgical team should be considered
      essential for performing the Excimer Laser Sheath Lead Extraction safely.

PMID- 21947649
TI  - Diagnostic criteria for IgG4-related sclerosing cholangitis based on
      cholangiographic classification.
AB  - BACKGROUND: IgG4-related sclerosing cholangitis (IgG4-SC) needs to be
      differentiated from pancreatic cancer (PCa), primary sclerosing cholangitis
      (PSC), and cholangiocarcinoma (CC). We attempted to establish diagnostic criteria
      for IgG4-SC based on cholangiographic classification by comparison with several
      diagnostic modalities. METHODS: We classified 62 IgG4-SC patients into three
      groups on the basis of cholangiographic findings to allow differentiation from
      PCa, PSC, and CC: Group A IgG4-SC showed features similar to PCa (Type 1, n =
      32), Group B showed similarity to PSC (Type 2, n = 15), and Group C showed
      similarity to CC (Type 3, 4, n = 15). Thirty-five patients with PCa, 40 with PSC,
      and 32 CC were enrolled as controls. We retrospectively compared the clinical,
      imaging, serological, and histopathological features and involvement of other
      organs between Group A and PCa, Group B and PSC, and Group C and CC. RESULTS:
      Association with autoimmune pancreatitis (AIP) (P < 0.001) and involvements with
      other organs (specificity 100%) were common useful diagnostic parameters in all
      three IgG4-SC groups. A high serum IgG4 level was a useful parameter in Groups A
      and B (P < 0.001). Discriminant analysis of cholangiograms (P < 0.001), liver
      biopsy (specificity 100%), and exclusion of inflammatory bowel disease
      (specificity 100%) were useful parameters in Group B. Intraductal ultrasonography
      findings (P < 0.001) and exclusion of malignancy by bile duct biopsy (specificity
      100%) were useful parameters in Group C. We established diagnostic criteria for
      IgG4-SC (sensitivity 100%, specificity 96.3%) by incorporating parameters that
      showed P < 0.001 or 100% specificity. CONCLUSIONS: Diagnostic criteria for IgG4
      SC based on cholangiographic classification are useful for distinguishing it from
      PCa, PSC, and CC.

PMID- 21947651
TI  - The in vitro and in vivo effects of human umbilical cord mesenchymal stem cells
      on the growth of breast cancer cells.
AB  - The purpose of the study was to detect the effect and possible mechanism of human
      umbilical cord mesenchymal stem cells (hUCMSCs) on the in vitro and in vivo
      growth of stem cells isolated from primary human breast cancer cells and cell
      lines MDA-MB-231 and MCF-7. Primary human breast cancer cells and MDA-MB-231 and
      MCF-7 cells were sorted in vitro using flow cytometry, and the ESA+, CD44+, CD24
      /low cells were isolated as breast cancer stem cells (CSCs). The inhibitory
      effect of hUCMSCs on CSCs was examined using the Cell Counting Kit-8 cell
      proliferation and soft agar colony formation assay. In vivo tumor inhibition was
      studied using a severe combined immunodeficient xenograft mouse model
      transplanted with MDA-MB-231 breast CSCs. The expression of phosphoinositide 3
      kinase (PI3K) and AKT was examined in the xenograft tumors using
      immunohistochemistry. The number of colonies formed by breast CSCs co-cultured
      with hUCMSCs at the bottom of soft agar was significantly lower than those formed
      by the control group (P < 0.01). Compared with the control group, the CSCs co
      cultured with hUCMSCs showed a higher number of cells in the G2-M phase (P <
      0.05) and an increased number of apoptotic cells (P < 0.01). The mice in the
      medium- and high-concentration hUCMSC treatment groups exhibited clearly reduced
      tumor volume and tumor weight, compared with the control group (P < 0.01).
      Compared with the saline group, the xenograft tumor tissues from the mice treated
      with different concentrations of hUCMSCs showed significantly reduced levels of
      PI3K and AKT proteins (P < 0.001). In conclusion, hUCMSC significantly inhibited
      the growth of breast CSCs in vitro and in vivo. The underlying mechanism is
      likely related to cell cycle arrest, induction of tumor cell apoptosis, and
      suppressed activities of PI3K and AKT protein kinases.

PMID- 21947652
TI  - The rearranged during transfection/papillary thyroid carcinoma tyrosine kinase is
      an estrogen-dependent gene required for the growth of estrogen receptor positive
      breast cancer cells.
AB  - The rearranged during transfection/papillary thyroid carcinoma (RET/PTC) tyrosine
      kinase is an oncogene implicated in the tumorigenesis of thyroid cancer. Recent
      studies by us and others have shown that RET/PTC kinase expression is induced by
      estrogen in breast cancer cells. Due to the critical involvement of estrogen
      regulated genes in the pathogenesis of breast cancer, we investigated the
      expression, regulation, and function of RET/PTC kinase in breast cancer cells. We
      found that RET/PTC kinase expression correlates with estrogen receptor (ER)
      expression in breast cancer cells and tumor specimens, and that RET/PTC kinase
      expression is associated with a poor prognosis in ER-positive breast cancer
      patients. We found that estrogen rapidly induces RET/PTC kinase expression in an
      ER-dependent manner in breast cancer cells and that this induction is through a
      transcriptional regulatory mechanism. Using reporter assays, small interfering
      RNA (siRNA) assays, and chromatin immunoprecipitation (ChIP) assays, we
      demonstrated the necessity of crosstalk between ER and the forkhead box A1
      (FOXA1) transcription factor in regulating RET/PTC kinase expression. In
      functional studies, increased expression of RET/PTC kinase induced by estrogen
      stimulation resulted in elevated phosphorylation of multiple downstream kinase
      signaling pathways. Conversely, knockdown of RET/PTC expression was associated
      with the inhibition of these same kinase signaling pathways, and, in fact,
      decreased the stimulatory effect of estrogen on the proliferation of ER-positive
      breast cancer cells. These results demonstrate a novel pathway of ER and FOXA1
      transcription factor crosstalk in regulating RET/PTC kinase expression, and
      demonstrate that RET/PTC kinase is a critical regulator for the proliferation of
      ER-positive breast cancer cells. Taken together, our study suggests that RET/PTC
      kinase may serve as a novel prognostic biomarker and therapeutic target for
      prevention and treatment of ER-positive breast cancer.

PMID- 21947653
TI  - Dying well with dementia: qualitative examination of end-of-life care.
AB  - BACKGROUND: People with dementia often die badly, receiving end-of-life care of
      poorer quality than that given to those who are cognitively intact. AIMS: To
      define good end-of-life care for people with dementia and identify how it can be
      delivered across care settings in the UK. METHOD: In-depth interviews were
      conducted with 27 bereaved family carers and 23 care professionals recruited from
      the community, care homes, general hospitals and continuing care units. Data were
      analysed using the constant comparison method. RESULTS: The data highlighted the
      challenge and imperative of 'dementia-proofing' end-of-life care for people with
      dementia. This requires using dementia expertise to meet physical care needs,
      going beyond task-focused care and prioritising planning and communication with
      families. CONCLUSIONS: The quality of end-of-life care exists on a continuum
      across care settings. Together, the data reveal key elements of good end-of-life
      care and that staff education, supervision and specialist input can enable its
      provision.

PMID- 21947654
TI  - Cannabis, COMT and psychotic experiences.
AB  - BACKGROUND: A putative interaction between cannabis and variation at rs4680
      within the catechol-methyl-transferase (COMT) gene on psychosis has been
      reported, but not adequately replicated. AIMS: To examine whether the relative
      risk of developing psychosis following use of cannabis is dependent upon
      variation within COMT. METHOD: A longitudinal study of 2630 individuals from the
      Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort who
      completed questionnaire-based assessments for cannabis use at age 14 and incident
      psychotic experiences at age 16. Six SNPs within COMT were genotyped. RESULTS:
      There was no evidence of an interaction under multiplicative models between
      cannabis use and COMT on the risk of developing psychotic experiences in our
      primary analyses. In sensitivity analyses we observed highly variable evidence of
      interaction, whereby psychotomimetic effects of cannabis were greater in
      methionine homozygotes under some scenarios, but in valine homozygotes under
      others. CONCLUSIONS: Cannabis increases risk of psychosis irrespective of
      underlying COMT genotypes. These findings argue against the widely held belief
      that the relative risk of developing psychosis following use of cannabis is
      dependent upon variation within COMT. The public health message about the
      potential increase in risk of psychotic disorders following cannabis use should
      not be tempered by reports that this harm is subgroup specific in the absence of
      robust evidence of replication.

PMID- 21947655
TI  - Cost utility of behavioural activation delivered by the non-specialist.
AB  - Behavioural activation by non-specialists appears effective in the treatment of
      depression. We examined incremental cost-effectiveness of behavioural activation
      (n = 24) v. treatment as usual (n = 23) in a randomised controlled trial.
      Intention-to-treat analyses indicated a quality-adjusted life-year (QALY)
      difference in favour of behavioural activation of 0.20 (95% CI 0.01-0.39, P =
      0.042), incremental cost-effectiveness ratio of L5756 per QALY and a 97%
      probability that behavioural activation is more cost-effective at a threshold
      value of L20,000. Results are promising for dissemination of behavioural
      activation but require replication in a larger study.

PMID- 21947656
TI  - Comparing the psychometric properties of the EQ-5D-3L and EQ-5D-5L in cancer
      patients in Korea.
AB  - PURPOSE: This study was conducted to assess the redistribution properties of the
      EQ-5D-3L when using the EQ-5D-5L and to compare the validity, informativity, and
      reliability of both EQ-5D-3L and EQ-5D-5L in Korean cancer patients. METHODS:
      Patients visiting one ambulatory cancer center self-administered the two versions
      of the EQ-5D and the EORTC QLQ-C30 questionnaire. Redistribution properties in
      each dimension of EQ-5D were analyzed between EQ-5D-3L and EQ-5D-5L.
      Informativity was evaluated using the Shannon entropy and ceiling effect.
      Convergent validity was evaluated by comparing the EQ-VAS, ECOG performance
      status, and EORTC QLQ-C30 subscales. Reliability was also evaluated in terms of
      test-retest reliability. RESULTS: All levels of the EQ-5D-3L substantially
      partitioned into associated levels of the EQ-5D-5L. The average inconsistency
      rate of the two versions was 3.5%. Absolute informativity was higher for the EQ
      5D-5L than for the EQ-5D-3L, but their informative efficiency tended to be
      similar. The proportion of 'perfect health' (11111) decreased from 16.8% in the
      EQ-5D-3L to 9.7% in the EQ-5D-5L. EQ-5D-5L demonstrated similar or higher
      correlations with the EQ-VAS, ECOG performance status, and EORTC QLQ-C30, than
      the EQ-5D-3L. The intraclass correlation coefficient of the EQ-5D-5L index was
      0.77. CONCLUSIONS: The EQ-5D-5L had greater informativity and lower rate in the
      ceiling effect than those values of the EQ-5D-3L. The EQ-5D-5L showed good
      construct validity and reasonable reliability. Therefore, considering these
      findings, the EQ-5D-5L may be preferable to the EQ-5D-3L.

PMID- 21947657
TI  - Development and psychometric evaluation of the public health surveillance well
      being scale.
AB  - PURPOSE: To develop and psychometrically evaluate the brief Public Health
      Surveillance Well-Being Scale (PHS-WB) that captures mental, physical, and social
      components of well-being. METHODS: Using data from 5,399 HealthStyles survey
      respondents, we conducted bi-factor, item response theory, and differential item
      functioning analyses to examine the psychometric properties of a pool of 34 well
      being items. Based on the statistical results and content considerations, we
      developed a brief 10-item well-being scale and assessed its construct validity
      through comparisons of demographic subgroups and correlations with measures of
      related constructs. RESULTS: Based on the bi-factor analyses, the items grouped
      into both an overall factor and individual domain-specific factors. The PHS-WB
      scale demonstrated good internal consistency (alpha = 0.87) and correlated highly
      with scores for the entire item pool (r = 0.94). The well-being scale scores
      differed as expected across demographic groups and correlated with global and
      domain-specific measures of similar constructs, supporting its construct
      validity. CONCLUSION: The 10-item PHS-WB scale demonstrates good psychometric
      properties, and its high correlation with the item pool suggests minimal loss of
      information with the use of fewer items. The brief PHS-WB allows for well-being
      assessment on national surveys or in other situations where a longer form may not
      be feasible.

PMID- 21947658
TI  - Repeated short-term stress synergizes the ROS signalling through up regulation of
      NFkB and iNOS expression induced due to combined exposure of trichloroethylene
      and UVB rays.
AB  - Restraint stress is known to catalyse the pathogenesis of the variety of chronic
      inflammatory disorders. The present study was designed to evaluate the effect of
      repeated short-term stress (RRS) on cellular transduction apart from oxidative
      burden and early tumour promotional biomarkers induced due to combined exposure
      of trichloroethylene (TCE) and Ultra-violet radiation (UVB). RRS leads to the
      increase in the expression of the stress responsive cellular transduction
      elements NFkB-p65 and activity of iNOS in the epidermal tissues of mice after
      toxicant exposure. RRS augments the steep depletion of the cellular antioxidant
      machinery which was evidenced by the marked depletion in GSH (Glutathione and GSH
      dependant enzymes), superoxide dismutase and catalase activity that were observed
      at significance level of P < 0.001 with increase in lipid peroxidation, H(2)O(2)
      and xanthine oxidase activity (P < 0.001) in the stressed animals and down
      regulation of DT-diaphorase activity (P < 0.001). Since, the induction of NFkB
      p65 and inducible nitric oxide synthase expression mediated can lead to the
      hyperproliferation, we estimated a significant increment (P < 0.001) in the
      synthesis of polyamines in mice skin evidenced here by the ornithine
      decarboxylase which is the early marker of tumour promotion and further evaluated
      PCNA expression. All these findings cues towards the synergising ability of
      repeated short-term stress in the toxic response of TCE and UVB radiation.

PMID- 21947659
TI  - Cardiac dysfunction subsequent to chronic ozone exposure in rats.
AB  - A number of advancements have been made toward identifying the risk factors
      associated with cardiovascular disease (CVD) and have resulted in a decline in
      mortality. However, many patients with cardiac disease show no established
      previous risk. Thus, it appears that other unknown factors contribute to the
      pathophysiology of CVD. Out of 350,000 sudden cardiac deaths each year in the
      United States, 60,000 deaths have been linked to air pollution, suggesting a
      detrimental role of environmental pollutants in the development of CVD. This
      study tested the hypothesis that chronic ozone (O(3)) exposure diminishes
      myocardial function in healthy population. Male Sprague-Dawley rats were exposed
      8 h/day for 28 and 56 days to filtered air or 0.8 ppm O(3). In vivo cardiac
      function was assessed by measuring LVDP, +dP/dt, -dP/dt, and LVEDP 24 h after
      termination of the O(3) exposure. Compared to rats exposed to filtered air, LVDP,
      +dP/dt, and -dP/dt were significantly decreased, and LVEDP was significantly
      increased in O(3) exposed animals. This attenuation of cardiac function was
      associated with increased myocardial TNF-alpha levels and lipid peroxidation as
      well as decreased myocardial activities of superoxidase dismutase and interleukin
      10 levels. These novel findings suggest myocardial dysfunction subsequent to
      chronic O(3) exposure in normal adult rats may be associated with a decrease in
      antioxidant reserve and with an increased production of inflammatory mediators.

PMID- 21947660
TI  - Association between antimicrobial consumption and clinical isolates of
      methicillin-resistant Staphylococcus aureus: a 14-year study.
AB  - The objective of this study was to determine the relationship between clinical
      isolates of methicillin-resistant Staphylococcus aureus (MRSA) and antimicrobial
      consumption in hospitalized patients over a 14-year period. The study was
      retrospectively conducted between January 1995 and December 2008 at Juntendo
      University Hospital, Tokyo, Japan, a 1,020-bed tertiary-care teaching hospital.
      The incidence of MRSA isolates was examined using clinical specimens presented to
      the microbiology laboratory in the hospital. Antimicrobial consumption through
      intravenous injection was calculated in terms of the number of defined daily
      doses per 100 bed-days. The correlation between the incidence of MRSA isolates
      and antimicrobial consumption was determined employing a multiple stepwise
      regression analysis. A total of 109,946 bacterial isolates were consecutively
      collected over the 14-year period, and, of these, 13,872 (64% of S. aureus
      strains excluding coagulase-negative staphylococci) were MRSA strains. The
      longitudinal observation showed that the number and rate of MRSA isolates
      marginally decreased. The rate of MRSA isolates among S. aureus strains in 1995
      was 68.5%, whereas that in 2008 was 53.8%. Consumption of cephalosporins
      decreased. Among carbapenems, the rate of imipenem (IPM) consumption decreased,
      whereas that of meropenem increased. A multiple stepwise regression analysis
      revealed that the antimicrobial consumption of cefmetazole, cefotiam, and IPM was
      positively correlated with the incidence of MRSA isolates. The use of beta-lactam
      antimicrobials may contribute to the development of MRSA strains.

PMID- 21947661
TI  - Increased concentrations of both NMDA receptor co-agonists D-serine and glycine
      in global ischemia: a potential novel treatment target for perinatal asphyxia.
AB  - Worldwide, perinatal asphyxia is an important cause of morbidity and mortality
      among term-born children. Overactivation of the N-methyl-D-aspartate receptor
      (NMDAr) plays a central role in the pathogenesis of cerebral hypoxia-ischemia,
      but the role of both endogenous NMDAr co-agonists D-serine and glycine remains
      largely elusive. We investigated D-serine and glycine concentration changes in
      rat glioma cells, subjected to oxygen and glucose deprivation (OGD) and CSF from
      piglets exposed to hypoxia-ischemia by occlusion of both carotid arteries and
      hypoxia. We illustrated these findings with analyses of cerebrospinal fluid (CSF)
      from human newborns affected by perinatal asphyxia. Extracellular concentrations
      of glycine and D-serine were markedly increased in rat glioma cells exposed to
      OGD, presumably through increased synthesis from L-serine. Upon reperfusion
      glycine concentrations normalized and D-serine concentrations were significantly
      lowered. The in vivo studies corroborated the finding of initially elevated and
      then normalizing concentrations of glycine and decreased D-serine concentrations
      upon reperfusion These significant increases of both endogenous NMDAr co-agonists
      in combination with elevated glutamate concentrations, as induced by global
      cerebral ischemia, are bound to lead to massive NMDAr activation, excitotoxicity
      and neuronal damage. Influencing these NMDAr co-agonist concentrations provides
      an interesting treatment target for this common, devastating and currently poorly
      treatable condition.

PMID- 21947662
TI  - Outcomes associated with a cognitive-behavioral chronic pain management program
      implemented in three public HIV primary care clinics.
AB  - In patients with HIV/AIDS, chronic pain is common and analgesics pose serious
      risks. Cognitive-behavioral therapies (CBT) provide an alternative. This study
      evaluated feasibility and impact of a CBT-based pain management program in three
      public primary care clinics for HIV patients. The program included a workbook and
      12-weeks of group CBT sessions. HIV-positive patients with chronic moderate to
      severe pain were invited to participate in the program and were assessed at
      enrollment, 6, 12, and 24 weeks. Despite only moderate group attendance, program
      enrollment was associated with significant improvements in pain intensity, pain
      related functioning, anxiety and acceptance, and mental health. At 24 weeks,
      effect sizes for pain outcomes were -0.83 for pain intensity and -0.43 for
      functioning. The pattern of change in outcomes was consistent with predictions
      based on cognitive-behavioral theory. Effects were observed at all clinics.
      Adding CBT-based pain management into primary care may provide important benefits
      for patients with HIV/AIDS.

PMID- 21947663
TI  - Sex differences in autism spectrum disorder: evidence from a large sample of
      children and adolescents.
AB  - Sex differences have been found amongst toddlers and young children with autism
      spectrum disorder (ASD). We investigated the presence and stability of these ASD
      sex differences throughout childhood and adolescence. Participants (N = 325, 52
      females; aged 3-18 years) consecutively received an ASD diagnosis at a clinic for
      assessing high-functioning ASD (mean verbal IQ = 92.6). There were no IQ sex
      differences. By parent report and direct observation, females had less repetitive
      stereotyped behaviour (RSB), with male-equivalent levels of social and
      communication impairment. Teachers reported males with ASD as having greater
      externalising and social problems than females. The female phenotype we describe
      was stable across our sample's age range. Their milder RSBs and less severe
      difficulties at school may lead to under-recognition of ASD in females.

PMID- 21947664
TI  - Behavioral activation and inhibition, negative affect, and gambling severity in a
      sample of young adult college students.
AB  - The prevalence of pathological gambling among college students is increasing. Few
      studies have directly examined the relation between reward processing and
      gambling severity while concurrently examining the effects of co-occurring
      negative affect in this at risk population. This study used Structural Equation
      Modeling (SEM) techniques to analyze results from an online survey of 352 female
      and 96 male students age 18-25. Participants completed measures of past year
      gambling behavior and severity of gambling problems using the Canadian Problem
      Gambling Index and the Problem Gambling Severity Index. Negative affect and
      reward processing were measured by the 21-item version of the Depression,
      Anxiety, and Stress Scales and the Behavioral Inhibition System and Behavioral
      Activation System (BIS/BAS) scales, respectively. Thirty-five percent of
      participants reported gambling in the previous 12 months, and 11% had gambling
      severity scores indicative of "moderate-risk" or "problem gambling." Gambling
      severity was associated with negative affect. Negative affect, in turn, was
      correlated with the unitary BIS scale and inversely associated with the BAS
      reward responsiveness scale. Reward responsiveness was also inversely associated
      with gambling severity. In the SEM models, the association between reward
      responsiveness and gambling severity was mediated by negative affect among males
      but not among females. Potential explanations for these findings and their
      implications for addressing problem gambling are discussed.

PMID- 21947665
TI  - DIMINUTO 1 affects the lignin profile and secondary cell wall formation in
      Arabidopsis.
AB  - Brassinosteroids (BRs) play a crucial role in plant growth and development and
      DIMINUTO 1 (DIM1), a protein involved in BR biosynthesis, was previously
      identified as a cell elongation factor in Arabidopsis thaliana. Through promoter
      expression analysis, we showed that DIM1 was expressed in most of the tissue
      types in seedlings and sectioning of the inflorescence stem revealed that DIM1
      predominantly localizes to the xylem vessels and in the interfascicular cambium.
      To investigate the role of DIM1 in cell wall formation, we generated loss-of
      function and gain-of-function mutants. Disruption of the gene function caused a
      dwarf phenotype with up to 38 and 23% reductions in total lignin and cellulose,
      respectively. Metabolite analysis revealed a significant reduction in the levels
      of fructose, glucose and sucrose in the loss-of-function mutant compared to the
      wild type control. The loss-of-function mutant also had a lower S/G lignin
      monomer ratio relative to wild type, but no changes were detected in the gain-of
      function mutant. Phloroglucinol and toluidine blue staining showed a size
      reduction of the vascular apparatus with smaller and disintegrated xylem vessels
      in the inflorescence stem of the loss-of-function mutant. Taken together, these
      data indicate a role for DIM1 in secondary cell wall formation. Moreover, this
      study demonstrated the potential role of BR hormones in modulating cell wall
      structure and composition.

PMID- 21947666
TI  - Biological responses of maize (Zea mays) plants exposed to chlorobenzenes. Case
      study of monochloro-, 1,4-dichloro- and 1,2,4-trichloro-benzenes.
AB  - A 7-day-exposure time experiment was designed to investigate the phytotoxicity of
      chlorobenzenes (CBs) on Zea mays seedlings, focusing on the growth and generation
      of oxidative stress. Significant growth inhibition (based on biomass gain) was
      observed for exposure to monochlorobenzene (MCB), dichlorobenzene (DCB) and
      trichlorobenzene (TCB) concentrations higher than 10 mg l(-1). It would seem that
      CBs inhibit cell division, since the mitotic index decreased for roots exposed to
      DCB at 80 mg l(-1) dose (8%) and to all the TCB concentrations tested (20%
      inhibition). CBs exposure resulting in an increase in the oxidative stress
      response in maize seedlings [reactive oxygen species like H(2)O(2), antioxidant
      enzymes (POD, GR), lipid peroxidation] correlated to the compound's degree of
      chlorination, where damage increasing with the number of chlorine atoms (MCB <
      DCB < TCB). This biological response was also dependent on the dose-exposure. Z.
      mays exposed to CBs at concentrations <10 mg l(-1) did not induce sufficient
      oxidative damage to cause root cell death. Therefore, CBs at current
      environmental concentrations are unlikely to produce evident phytotoxic effects
      on Z. mays seedlings.

PMID- 21947667
TI  - Mercury in non-breeding sparrows of North Carolina salt marshes.
AB  - We captured Nelson's, Saltmarsh and Seaside Sparrows (Ammodramus nelsoni, A.
      caudacutus and A. maritimus) at three salt marsh sites near Wrightsville Beach,
      North Carolina during five non-breeding seasons (September through April, 2006
      2011). We analyzed breast feather samples from all of these seasons and blood and
      first primary feather (P1) samples from three seasons (2008-2011) for mercury
      (Hg). Generalized linear models were used to test for the impact of species,
      season, site and month on blood Hg, species, season and site on P1 Hg and species
      and season on breast feather Hg. The best-fit model for blood indicated that Hg
      varied among species, seasons and months. Saltmarsh Sparrows maintain higher
      blood Hg than Nelson's and Seaside Sparrows during the non-breeding season while
      they are feeding in mixed flocks. In Nelson's and Seaside Sparrows, blood Hg
      decreased during mid-winter compared to early fall and late spring. Breast
      feather and P1 Hg varied among species with Saltmarsh Sparrows exhibiting higher
      concentrations than the other two species, while Nelson's Sparrows had lower
      concentrations than the other two species. Breast feather Hg was higher in the
      final three seasons than in the first two. Our results indicate that Hg exposure
      on breeding sites may be increasing and that high levels of Hg exposure during
      the breeding season may affect blood Hg concentrations year-round in Saltmarsh
      Sparrows. Our data thus provide a baseline for future Hg assessments in these
      species in NC.

PMID- 21947670
TI  - Outcomes after robot-assisted pancreaticoduodenectomy for periampullary lesions.
AB  - BACKGROUND: There are many theoretical advantages that a minimally invasive
      approach to the pancreaticoduodenectomy might offer patients with benign and
      malignant disease of the head of the pancreas over traditional open techniques,
      including improved recovery time, decreased hospital stay, and earlier initiation
      of and higher rate of completion of adjuvant therapy. The goal of this study was
      to assess the oncologic and safety outcomes after a robot-assisted approach to
      pancreaticoduodenectomy. METHODS: Retrospective review of a prospectively
      acquired database of robot-assisted pancreaticoduodenectomy (RAPD) for
      periampullary lesions between October 2008 and December 2010. RESULTS: Fifty
      patients underwent attempted RAPD. Conversion to open procedure was required in
      eight patients (16%). At intention-to-treat analysis, pancreatic fistula as
      defined by the International Study Group of Pancreatic Surgery occurred in 10
      patients (20%). Most patients experienced either no (21, 42%) postoperative
      complications or minor Clavien I/II events (13, 26%). Major morbidity (Clavien
      III/IV) occurred in 15 patients (30%). The margin-negative resection rate was
      89%, and the median number of lymph nodes collected was 18. Fifteen patients met
      the eligibility criteria for adjuvant chemotherapy after surgery. Eleven (73.3%)
      of 15 eligible patients were treated with adjuvant therapy at a mean of 11.5
      weeks after surgery. CONCLUSIONS: RAPD can be performed with safety and oncologic
      outcomes comparable to open or laparoscopic approaches. Results of this early
      series suggest that the robot-assisted approach holds promise. Larger, more
      mature multi-institutional cohorts will be needed to explore potential benefits
      over open and laparoscopic techniques.

PMID- 21947671
TI  - MagT1: a highly specific magnesium channel with important roles beyond cellular
      magnesium homeostasis.
AB  - Over recent years, the study of magnesium homeostasis has greatly benefited from
      molecular genetic approaches that identified several new classes of magnesium
      transporters. These proteins demonstrate a diversity of structural properties and
      biophysical functions that often translate into a wide range of tissue-specific
      cellular activities. Among these novel channels, MagT1 has gained most of the
      attention, given its high selectivity for Mg(2+) and its possible involvement in
      cellular functions reaching far beyond magnesium homeostasis, as the latest
      findings seem to imply. Indeed, a signaling role for MagT1 has been proven in T
      lymphocytes, where Mg(2+) functions as a second messenger, coupling TCR
      activation to intracellular effectors. We herein review these intriguing results
      and discuss their potential implications for magnesium research, and ultimately
      for therapeutic opportunities. As our knowledge of magnesium advances, it becomes
      increasingly clear that a deeper understanding of magnesium homeostasis is the
      key for a deeper insight into relevant pathophysiological conditions, and their
      treatment.

PMID- 21947668
TI  - Single and combined effects of selected pharmaceuticals at sublethal
      concentrations on multiple biomarkers in Carassius auratus.
AB  - In this study, the sublethal effects of caffeine, sulfamethoxazole and their
      mixture on goldfish (Carassius auratus) were investigated, the biomarkers
      including acetylcholinesterase (AChE) in brain, 7-ethoxyresorufin O-deethylase
      (EROD), glutathione S-transferase (GST) and superoxide dismutase (SOD) in liver
      and vitellogenin (VTG) in serum were determined after 1, 2, 4, and 7 days of
      exposure. AChE activity was significantly inhibited by caffeine (>=0.4 mg/l),
      sulfamethoxazole (>=0.4 mg/l) and their mixtures (>=0.048 mg/l) during all
      exposure periods, and obvious concentration-response and time-response
      relationships were obtained. EROD, GST and SOD activities were significantly
      increased by individual compounds and mixtures in most cases. GST induction
      exhibited bell-shaped concentration-response curves. Serum VTG was significantly
      induced by 2 mg/l of caffeine, 10 mg/l of sulfamethoxazole and the mixtures at
      concentrations >=1.2 mg/l. In general, the two pharmaceuticals induced similar
      biological responses. The joint effect of caffeine/sulfamethoxazole was additive
      with regard to AChE and GST activity variation and was antagonistic with regard
      to EROD and SOD induction. The results indicated that multiple biomarker response
      method might be a useful tool for describing an integrated toxicological effect
      of chemicals. VTG induction suggested that caffeine and sulfamethoxazole may
      cause a slightly feminization effect.

PMID- 21947672
TI  - Glycine feeding improves pristinamycin production during fermentation including
      resin for in situ separation.
AB  - Seven amino acids were tested as precursors to affect pristinamycin production by
      a mutant strain derived from Streptomyces pristinaespiralis ATCC25486. Of those,
      glycine was selected as the best precursor to facilitate both cell growth and
      pristinamycin production at the feeding time of 36-h incubation and the feeding
      rate of 0.75 g L(-1) flask culture. The optimized time and concentration of
      glycine feeding were applied to enlarged 3-L bioreactor fermentation with a resin
      added at the time of 20-h fermentation for in situ separation. As a result, a
      combination of the glycine feeding and the added resin resulted in the maximal
      pristinamycin yield of 616 mg L(-1) culture 12 h after glycine feeding. The yield
      from the combined treatment was 1.71-, 2.77- and 4.32-fold of those from the mere
      glycine and resin treatments and the control, respectively. Other parameters,
      including intracellular nucleic acid content, animo nitrogen content and pH
      level, during 72-h fermentation were also given in association with the
      pristinamycin yields in the different treatments. The results indicate that
      glycine feeding is an effective approach to enhance pristinamycin production in
      the culture of S. pristinaespiralis F213 with supplemented resin for in situ
      separation.

PMID- 21947673
TI  - Optimization of the mated fermentation process for the production of lycopene by
      Blakeslea trispora NRRL 2895 (+) and NRRL 2896 (-).
AB  - The mated fermentation process for the production of lycopene by Blakeslea
      trispora NRRL 2895 (+) and NRRL 2896 (-) was systematically optimized in shake
      flasks. The ratio of the (+) to (-) strains, the lycopene cyclase inhibitors
      piperidine and creatinine, the trisporic acid structural analog abscisic acid,
      the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) precursor leucine, and the
      mevalonate kinase enhancer penicillin were all identified as key factors
      affecting lycopene biosynthesis. With an optimal ratio of 5:1 for the (+) to (-)
      strains and the addition of 6 g/L creatinine on day 3, the highest lycopene
      production was 98.1 +/- 15.5 mg/L. Based on the above result, the addition of 0.1
      g/L penicillin on day 4, 150 MUmol/L abscisic acid on day 3 or 0.5 g/L leucine on
      day 4 enhanced lycopene production to 119.7 +/- 17.2, 120.6 +/- 12.3 and 135.2 +/
      7.0 mg/L, respectively. Finally, an integrated strategy by combining the above
      key factors was developed, and the highest lycopene production of 156.2 +/- 15.4
      mg/L was obtained, which was enhanced by 134.9% comparing with its production of
      66.5 +/- 3.6 mg/L before the optimization process of this work. The results
      obtained in this study may be useful for large-scale industrial lycopene
      production.

PMID- 21947674
TI  - Blood glucose control using an artificial pancreas reduces the workload of ICU
      nurses.
AB  - Blood glucose management is one of the important therapies in the intensive care
      unit (ICU). However, blood glucose management using the sliding-scale method
      increases the workload of ICU nurses. An artificial pancreas, STG-22, has been
      developed to continuously monitor blood glucose levels and to maintain them at
      appropriate levels. In this study, we examined the hypothesis that compared to
      conventional methods, blood glucose management using the STG-22 reduces the
      workload of ICU nurses and has a positive impact on awareness regarding the
      management of blood glucose. This study included 45 patients who underwent
      elective surgery and were treated at the ICU postoperatively. The patients were
      separated into the following two groups: (1) blood glucose was maintained using
      the STG-22 (AP group) and (2) blood glucose was maintained using the sliding
      scale method (SS group). In addition, a questionnaire was developed for an
      awareness survey of ICU nurses (N = 20). The frequency of blood sampling and
      number of double checks were significantly lower in the AP group (1.3 +/- 1.4 vs.
      8.9 +/- 8.1 times/admission, P < 0.001; 1.0 +/- 1.4 vs. 9.8 +/- 8.5
      times/admission, P < 0.001). The time needed for glucose management per admission
      was significantly shorter in the AP group (9 +/- 13 vs. 27 +/- 24 min/admission;
      P = 0.003). Use of STG-22 for glucose management in the ICU increased the degree
      of attention given by nurses to glucose management and contributed to an improved
      sense of security. In conclusion, using the STG-22 in the ICU reduces the
      workload of ICU nurses compared to using the sliding-scale method. It also
      contributed to the reduction of the ICU nurses' anxiety related to the management
      of blood glucose.

PMID- 21947675
TI  - Degradation and elimination of succinylcholine and succinylmonocholine and
      definition of their respective detection windows in blood and urine for forensic
      purposes.
AB  - The muscle relaxant succinylcholine (SUX) evokes respiratory paralysis, and
      numerous cases of fatal SUX intoxication have been reported. Detection of SUX and
      its metabolite succinylmonocholine (SMC) is difficult, both due to their (bis-)
      quaternary structure and the extreme hydrolytic susceptibility of SUX, and data
      on degradation kinetics of SUX and SMC is scarce. The present study investigates
      the in vivo and in vitro degradation as well as elimination of both target
      analytes using authentic blood and urine samples from anesthetized patients. With
      a special focus on the urinary data and stabilization issues, this work intends
      to considerably enhance the forensic knowledge concerning SUX intoxications and
      to present the reader with practical analytical strategies to cope with such
      difficult cases. Eighteen subjects undergoing surgery and requiring arterial as
      well as bladder catheters were included in this study. Muscle relaxation was
      initialized with a bolus injection of 80-100 mg SUX. Blood and urine samples were
      either collected using paraoxonized (n = 15) or non-modified (n = 3) tubes.
      Sampling was performed within 6 h after SUX application following a pre-assigned
      schedule. Samples were processed according to a validated isotope dilution HPLC
      MS/MS method using ion-pair solid-phase extraction. In blood, SUX was usually
      detectable for up to 10 min post-injection, while detection of SMC was possible
      over the whole observation period of 6 h. Effectiveness of organophosphate
      stabilization was proven for both analytes and is therefore recommended. In
      freshly secreted urine, detection windows of a minimum of 2 h as opposed to 6 h
      have been determined for SUX versus SMC, respectively. Considering SMC plasma
      kinetics, detection of the metabolite in blood and freshly secreted urine appears
      to be possible over a period of at least 8-24 h. Paraoxon did not enhance the
      stability of either target substance in urine, stabilization of urine samples is
      nonetheless recommended. In summary, SMC was proven to be the most promising
      target analyte in SUX analysis, with urine being the proposed matrix of choice
      for forensic applications. Furthermore, our work defines meaningful detection
      windows for SUX and SMC in blood and urine as routine matrices and presents
      sampling recommendations as well as guideline values for forensic toxicological
      analysis.

PMID- 21947677
TI  - Head-to-head comparison of the 70-gene signature versus the 21-gene assay: cost
      effectiveness and the effect of compliance.
AB  - Both the 70-gene signature and the 21-gene assay are novel prognostic tests used
      to guide adjuvant chemotherapy decisions in patients with early breast cancer.
      Although the results of ongoing prospective trials will only become available in
      some years, the tests have already been included in clinical guidelines such as
      St. Gallen's. In literature, the cost-effectiveness (CE) of both tests as
      compared to conventional prognostic tests has been described. We report on a
      direct comparison of CE; as different compliance rates were reported, we also
      taken these into account. A Markov decision model with a time horizon of 20 years
      was developed to assess the effects, costs and CE of three alternatives; 21-gene,
      70-gene, and St. Gallen (SG) or Adjuvant Online (AO), dependent on the dataset
      used in patients with early, node-negative, breast cancer. Sensitivity and
      specificity were based on two datasets, incorporating compliances rates based on
      literature. For both datasets, whereas the 70-gene signature yielded more quality
      adjusted life years (QALYs) and was less costly; the 21-gene amounted more life
      years (LYs) but was more costly. The decision uncertainty surrounding the
      probability of CE of the Thomassen-series amounted 55% for both cost/LY and
      cost/QALY, for the Fan-series 80% for LY and 65% for QALYs. Taking reported
      compliance with discordant test results into account, in general, the effect of
      all strategies decreased, while the costs increased, without relatively
      influencing the CEA performance. This comparison indicates that the performances
      of the 70-gene and the 21-gene based on reported studies are close. The 21-gene
      has the highest probability of being cost-effective when focusing on cost/LY,
      while focusing on cost/QALY, the 70-gene signature was most cost-effective. The
      level of compliance can have serious impact on the CE. With additional data,
      preferably from head-to-head outcome studies and especially on compliance
      concerning discordant test results, calculations can be made with higher degrees
      of certainty.

PMID- 21947678
TI  - Polymorphism Thr160Thr in SRD5A1, involved in the progesterone metabolism,
      modifies postmenopausal breast cancer risk associated with menopausal hormone
      therapy.
AB  - Menopausal hormone therapy (MHT) is associated with an increased breast cancer
      risk in postmenopausal women, with combined estrogen-progestagen therapy posing a
      greater risk than estrogen monotherapy. However, few studies focused on potential
      effect modification of MHT-associated breast cancer risk by genetic polymorphisms
      in the progesterone metabolism. We assessed effect modification of MHT use by
      five coding single nucleotide polymorphisms (SNPs) in the progesterone
      metabolizing enzymes AKR1C3 (rs7741), AKR1C4 (rs3829125, rs17134592), and SRD5A1
      (rs248793, rs3736316) using a two-center population-based case-control study from
      Germany with 2,502 postmenopausal breast cancer patients and 4,833 matched
      controls. An empirical-Bayes procedure that tests for interaction using a
      weighted combination of the prospective and the retrospective case-control
      estimators as well as standard prospective logistic regression were applied to
      assess multiplicative statistical interaction between polymorphisms and duration
      of MHT use with regard to breast cancer risk assuming a log-additive mode of
      inheritance. No genetic marginal effects were observed. Breast cancer risk
      associated with duration of combined therapy was significantly modified by
      SRD5A1_rs3736316, showing a reduced risk elevation in carriers of the minor
      allele (p (interaction,empirical-Bayes) = 0.006 using the empirical-Bayes method,
      p (interaction,logistic regression) = 0.013 using logistic regression). The risk
      associated with duration of use of monotherapy was increased by AKR1C3_rs7741 in
      minor allele carriers (p (interaction,empirical-Bayes) = 0.083, p
      (interaction,logistic regression) = 0.029) and decreased in minor allele carriers
      of two SNPs in AKR1C4 (rs3829125: p (interaction,empirical-Bayes) = 0.07, p
      (interaction,logistic regression) = 0.021; rs17134592: p (interaction,empirical
      Bayes) = 0.101, p (interaction,logistic regression) = 0.038). After Bonferroni
      correction for multiple testing only SRD5A1_rs3736316 assessed using the
      empirical-Bayes method remained significant. Postmenopausal breast cancer risk
      associated with combined therapy may be modified by genetic variation in SRD5A1.
      Further well-powered studies are, however, required to replicate our finding.

PMID- 21947676
TI  - Postmortem chemistry update part I.
AB  - Postmortem chemistry is becoming increasingly essential in the forensic pathology
      routine and considerable progress has been made over the past years. Biochemical
      analyses of vitreous humor, cerebrospinal fluid, blood and urine may provide
      significant information in determining the cause of death or in elucidating
      forensic cases. Postmortem chemistry may essentially contribute in the
      determination of the cause of death when the pathophysiological changes involved
      in the death process cannot be detected by morphological methods (e.g. diabetes
      mellitus, alcoholic ketoacidosis and electrolytic disorders). It can also provide
      significant information and useful support in other forensic situations,
      including anaphylaxis, hypothermia, sepsis and hormonal disturbances. In this
      article, we present a review of the literature that covers this vast topic and we
      report the results of our observations. We have focused our attention on glucose
      metabolism, renal function and electrolytic disorders.

PMID- 21947679
TI  - Use of high technology imaging for surveillance of early stage breast cancer.
AB  - Guidelines do not support utilization of high technology radiologic imaging
      (HTRI) for surveillance after curative treatment for early stage breast cancer.
      Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data were used
      to identify 25,555 women diagnosed with stage I-II breast cancer between 1998 and
      2003 who survived >= 48 months from diagnosis without evidence of second primary
      or recurrent cancer in this interval. HTRI utilization (computerized tomography
      scanning (CT), bone scan (BS), breast magnetic resonance imaging, and positron
      emission tomography scans) was measured in months 13-48 post-diagnosis. Cases
      were individually matched to 75,669 female Medicare enrollees without cancer.
      Factors associated with HTRI utilization were evaluated. Forty percent of women
      with stage I-II breast cancer and 25% of controls had >= 1 HTRI during the
      surveillance interval (P < 0.001). High utilization rates were observed for CT
      (30%) and BSs (19%). The proportion of women who had a CT during the surveillance
      period increased in both cancer survivors and controls. Among breast cancer cases
      age <80, higher comorbidity index, stage II disease, and more recent diagnosis
      were independently associated with receipt of HTRI. Paralleling patterns observed
      in controls, HTRI utilization for surveillance following diagnosis of early stage
      breast cancer has steadily increased among Medicare beneficiaries. Strategies to
      foster judicious utilization of HTRI should be a priority.

PMID- 21947680
TI  - A GINECO randomized phase II trial of two capecitabine and weekly paclitaxel
      schedules in metastatic breast cancer.
AB  - To determine whether capecitabine schedule adaptation improves the tolerability
      of capecitabine-paclitaxel combination therapy for metastatic breast cancer
      (MBC), patients with anthracycline-pretreated HER2-negative MBC were randomized
      to either arm A (21-day cycles: capecitabine 1,000 mg/m(2) twice daily, days 1
      14; paclitaxel 60 mg/m(2), days 1, 8, and 15) or arm B (28-day cycles:
      capecitabine 1,000 mg/m(2) twice daily, days 1-5, 8-12, and 15-19; paclitaxel 80
      mg/m(2), days 1, 8, and 15). The primary endpoint was the incidence of dose
      reductions or delays >1 week for grade 3/4 toxicity. Secondary endpoints were
      efficacy and safety. All 130 randomized patients were evaluable for safety. Dose
      reduction or delay for grade 3/4 toxicity occurred in 39% of patients in arm A
      and 34% in arm B during cycles 1-6. In arm A, there were significantly more
      toxicity-related dose reductions (cycles 1-6: 82 vs. 67%, respectively; P = 0.05)
      and discontinuations (29 vs. 8%, respectively). Grade 3 diarrhea occurred in 12
      and 0%, respectively, and grade 3 hand-foot syndrome in 12 versus 9%,
      respectively (grade 4 not applicable). There were no detectable differences in
      efficacy. Weekday capecitabine dosing with weekly paclitaxel may improve
      tolerability without a detrimental effect on efficacy, and merits further
      evaluation in patients suited to combination chemotherapy.

PMID- 21947681
TI  - Dose-adjustment study of tamoxifen based on CYP2D6 genotypes in Japanese breast
      cancer patients.
AB  - CYP2D6 is a key enzyme responsible for the metabolism of tamoxifen to active
      metabolites, endoxifen, and 4-hydroxytamoxifen. The breast cancer patients who
      are heterozygous and homozygous for decreased-function and null alleles of CYP2D6
      showed lower plasma concentrations of endoxifen and 4-hydroxytamoxifen compared
      to patients with homozygous-wild-type allele, resulting in worse clinical outcome
      in tamoxifen therapy. We recruited 98 Japanese breast cancer patients, who had
      been taking 20 mg of tamoxifen daily as adjuvant setting. For the patients who
      have one or no normal allele of CYP2D6, dosages of tamoxifen were increased to 30
      and 40 mg/day, respectively. The plasma concentrations of tamoxifen and its
      metabolites were measured at 8 weeks after dose-adjustment using liquid
      chromatography-tandem mass spectrometry. Association between tamoxifen dose and
      the incidence of adverse events during the tamoxifen treatment was investigated.
      In the patients with CYP2D6*1/*10 and CYP2D6*10/*10, the mean plasma endoxifen
      levels after dose increase were 1.4- and 1.7-fold higher, respectively, than
      those before the increase (P < 0.001). These plasma concentrations of endoxifen
      achieved similar level of those in the CYP2D6*1/*1 patients receiving 20 mg/day
      of tamoxifen. Plasma 4-hydroxytamoxifen concentrations in the patients with
      CYP2D6*1/*10 and CYP2D6*10/*10 were also significantly increased to the similar
      levels of the CYP2D6*1/*1 patients according to the increasing tamoxifen dosages
      (P < 0.001). The incidence of adverse events was not significantly different
      between before and after dose adjustment. This study provides the evidence that
      dose adjustment is useful for the patients carrying CYP2D6*10 allele to maintain
      the effective endoxifen level.

PMID- 21947682
TI  - The relationship between twin births and maternal risk of breast cancer: a meta
      analysis.
AB  - Women who undergo a greater number of menstrual cycles may be at increased risk
      of breast cancer, possibly due to cumulative exposure to ovarian hormones.
      Pregnancy reduces the lifetime number of menstrual cycles and also influences the
      levels of ovarian hormones. Twin pregnancies differ from singleton pregnancies in
      both hormone levels and perinatal changes. To date, a meta-analysis on the
      effects of twin birth on the risk of maternal breast cancer has not been
      conducted. Among 17 relevant publications identified in a systematic search, some
      suggest that twin births may be associated with lower breast cancer risk but
      others do not; therefore, the results are inconclusive. Although our pooled
      results of all 17 published studies did not show a reduced maternal risk of
      breast cancer for twin births (HR 0.94; 95% CI = 0.87-1.02; P = 0.127), a trend
      toward reduced maternal risk of breast cancer was identified in a subgroup
      analysis of cohort studies (HR 0.91; 95% CI = 0.83-1.01; P = 0.068). The results
      of this meta-analysis suggest that twin pregnancy does not significantly decrease
      the maternal risk of breast cancer.

PMID- 21947683
TI  - Simultaneous analysis of tumor and stromal gene expression profiles from
      xenograft models.
AB  - Identifying the gene expression alterations that occur in both the tumor and
      stroma is essential to understanding tumor biology. We have developed a dual
      species microarray analysis method that allows the dissection of both tumor and
      stromal gene expression profiles from xenograft models, based on limited
      interspecies cross-hybridization on Illumina gene expression beadchips. This
      methodology allows for simultaneous genome-wide analysis of gene expression
      profiles of both tumor cells and the associated stromal tissue.

PMID- 21947684
TI  - Abstracts of the 62nd Irish Cardiac Society Annual Scientific Meeting. October 6
      8, 2011. Newcastle, County Down, Northern Ireland.

PMID- 21947685
TI  - The spectrum of functional gastrointestinal disorders in a tertiary referral
      clinic in Ireland.
AB  - BACKGROUND: The functional gastrointestinal disorders (FGIDs) are a heterogenous
      group of chronic conditions which cause troubling gastrointestinal symptoms.
      Though common and sometimes disabling, causing considerable social and economic
      burden, there is little recent literature on presentation or impact of FGIDs in
      Ireland. AIM: To describe the characteristics of patients with FGIDs at a
      tertiary referral clinic in Ireland. METHODS: A retrospective review of those
      attending a university hospital gastroenterology clinic with a special interest
      in FGIDs between January 1999 and July 2008 was performed. Data were mined from
      electronic outpatient records and clinic letters. RESULTS: A total of 1,909
      patients were included. Of these patients, 41.2% (787 of 1,909) received a
      diagnosis of FGID. FGID patients were predominantly (70.14%) female and the
      average age at first presentation was 38.3 years. Of these, 76% (598 of 787) were
      referred from general practice; 35.8% (282 of 787) received onward referrals to
      other specialties. Nine hundred FGIDs were diagnosed. The most common FGID was
      irritable bowel syndrome (633 of 900, 70.3%). In the FGID group, 13.1% of
      patients (103 of 787) had more than one FGID diagnosis. Females received a
      definitive diagnosis of FGID faster than males; mean diagnostic latency: 5.3
      versus 6.4 months (p < 0.05). Sixty-six percent (523 of 787) of FGID patients had
      non-gastrointestinal co-morbidities, with 315 (60.2%) of these having more than
      one co-morbidity. The burden of non-GI co-morbidity was significantly higher in
      patients with overlapping functional syndromes than in patients with single FGID
      (p < 0.05). CONCLUSIONS: In Ireland, FGIDs are common, represent a significant
      burden for the health-care system and deserve greater recognition and further
      research attention.

PMID- 21947686
TI  - Managing chronic disease in Ireland: hospital admission rates and clinical
      outcomes in a large ulcerative colitis population.
AB  - BACKGROUND: Health care planning demands a detailed knowledge of the course of
      chronic diseases in the Irish population. This study describes hospital admission
      rates, medication use and outcomes in a large cohort of patients with ulcerative
      colitis attending a tertiary referral centre in Ireland. METHOD: Four hundred and
      twenty-four patients who attended during the 18-year period from January 1991 to
      January 2009 were identified. Baseline demographics, hospital admission,
      medications required, extent of colitis and date of colectomy were recorded.
      RESULTS: More than half (55.4%) of the patients were managed exclusively in an
      outpatient setting throughout diagnosis and follow-up. Systemic corticosteroids,
      thiopurines and infliximab were required by 70, 29.5 and 5% of the patients,
      respectively. Overall 5-year colectomy rate due to failure of medical therapy was
      15.8%. Independent predictors of colectomy were hospital admission at first
      presentation (odds ratio 3.6, p < 0.0001) and pancolitis at diagnosis (odds ratio
      2.3, p < 0.01). CONCLUSIONS: The majority of patients with colitis have an
      uncomplicated disease course and do not require thiopurines, biologic agents or
      hospital admission. Principal management at a primary care level may be
      appropriate in many cases. Colectomy rates at a specialist centre in Ireland
      compare favourably with international figures.

PMID- 21947688
TI  - Joint use of a chitosan/PLGA scaffold and MSCs to bridge an extra large gap in
      dog sciatic nerve.
AB  - BACKGROUND: Tissue-engineered nerve grafts (TENGs) constitute a promising
      alternative to nerve autografts that are recognized as the gold standard for
      surgical repair of peripheral nerve gaps. OBJECTIVE: To investigate the
      feasibility of using TENGs for bridging extra large peripheral nerve gaps in
      large animals. METHODS: TENGs were constructed by incorporating autologous bone
      marrow mesenchymal stem cells (MSCs) into a neural scaffold that consisted of a
      chitosan conduit inserted with poly(lactic-co-glycolic acid) (PLGA) fibers. A 60
      mm-long sciatic nerve gap in dogs was bridged by TENGs, chitosan/PLGA scaffolds,
      or nerve autografts. At 12 months postsurgery, behavioral analysis,
      electrophysiology, retrograde fluorogold tracing, and histological examination
      were performed. RESULTS: The outcomes of TENGs were similar to those of
      autografts and better than those of scaffolds alone. CONCLUSION: Introduction of
      autologous MSCs to a chitosan/PLGA scaffold improved the repair and
      rehabilitation of a large gap after peripheral nerve injury in dogs. Autologous
      MSCs may be a source of support cells for neural tissue engineering.

PMID- 21947687
TI  - Regular exercise prevents oxidative stress in the brain of hyperphenylalaninemic
      rats.
AB  - Phenylketonuria (PKU) is caused by deficiency of phenylalanine hydroxylase,
      leading to accumulation of phenylalanine and its metabolites. Clinical features
      of PKU patients include mental retardation, microcephaly, and seizures. Oxidative
      stress has been found in these patients, and is possibly related to
      neurophysiopatology of PKU. Regular exercise can leads to adaptation of
      antioxidant system, improving its capacity to detoxification reactive species.
      The aim of this study was to verify the effects of regular exercise on oxidative
      stress parameters in the brain of hyperphenylalaninemic rats. Animals were
      divided into sedentary (Sed) and exercise (Exe) groups, and subdivided into
      saline (SAL) and hyperphenylalaninemia (HPA). HPA groups were induced HPA through
      administration of alpha-methylphenylalanine and phenylalanine for 17 days, while
      SAL groups (n = 16-20) received saline. Exe groups conducted 2-week aerobic
      exercise for 20 min/day. At 18th day, animals were killed and the brain was
      homogenized to determine thiobarbituric acid reactives substances (TBA-RS)
      content, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase
      (GPx) activities. Soleus muscles were collected to determine glycogen content as
      a marker of oxidative adaptation. Exe groups showed enhanced glycogen content.
      HPA condition caused an increase in TBA-RS and SOD, and reduces CAT and GPx.
      Exercise was able to prevent all changes seen in the HPA group, reaching control
      values, except for SOD activity. No changes were found in the ExeSAL group
      compared to SedSAL. Hyperphenylalaninemic rats were more responsive to the
      benefits provided by regular exercise. Physical training may be an interesting
      strategy to restore the antioxidant system in HPA.

PMID- 21947689
TI  - Construction and international validation of CIVIQ-14 (a short form of CIVIQ-20),
      a new questionnaire with a stable factorial structure.
AB  - BACKGROUND: The factorial instability of the CIVIQ-20 social dimension in
      different populations has necessitated the development of a new stable
      questionnaire to interpret results from international studies. OBJECTIVE:
      Construction of a stable and psychometrically validated questionnaire from CIVIQ
      20. METHODS AND MAJOR FINDINGS: A prospective, international study was used to
      construct a stable CIVIQ scale and to validate its psychometric properties. An
      iterative process was implemented to eliminate the more unstable items (six), and
      the social and physical dimensions were combined. The resulting instrument
      comprised 14 items, split into three dimensions (pain, physical, and
      psychological), and was named CIVIQ-14. The stability of the CIVIQ-14 factorial
      structure was confirmed in Polish, Czech, Spanish, and French populations using
      principal component analysis and multitrait/multimethod analysis. Psychometric
      assessment demonstrated that CIVIQ-14 was reliable (intra-class coefficient >0.8;
      weighted kappa >0.8), valid (correlation coefficients between dimension scores
      and clinical severity scores between 0.3 and 0.6), and sensitive (effect sizes
      >0.6 for psychological dimension; >0.8 for the other dimensions). CONCLUSION:
      CIVIQ-14 is a reliable, valid, and sensitive instrument applicable to
      international studies of patients with chronic venous disease.

PMID- 21947690
TI  - Symptom assessment in ambulatory oncology: initial validation of the nurse
      developed Modified Ambulatory Care Flow Sheet (MACFS).
AB  - PURPOSE: This paper reports relationships between symptoms assessed using a newly
      developed instrument for assessing patient-reported symptoms, the Modified
      Ambulatory Care Flow Sheet (MACFS), and other symptom assessment measures.
      METHODS: Using a cross-sectional design, patients on active treatment for
      colorectal cancer were recruited in an ambulatory setting of a tertiary care
      cancer center in western Canada. Participants completed the European Organization
      for Research and Treatment of Cancer Quality of Life Questionnaire--Cancer 30,
      the Rotterdam Symptom Checklist Modified, Linear analog scales for pain and
      coping, and the MACFS, all at a single time point. RESULTS: We found moderate to
      strong correlations between the MACFS scores and scores on the other symptom
      measures used. The correlations were not as strong when using the MACFS symptom
      change scores, as when using the MACFS scores for the presence or absence of a
      particular symptom. CONCLUSIONS: The MACFS reflects the symptom experience of
      colorectal cancer patients. Further evaluation in more diverse populations and of
      the relationship between MACFS symptom scores and quality of life will improve
      our understanding of the MACFS and of the cancer patient treatment experience.

PMID- 21947691
TI  - Growth and asiaticoside production in multiple shoot cultures of a medicinal
      herb, Centella asiatica (L.) Urban, under the influence of nutrient
      manipulations.
AB  - Growth and in vitro asiaticoside accumulation in multiple shoot cultures of
      Centella asiatica (L.) Urban was studied as a function of nutrient manipulations
      in the culture media. Shoot cultures raised in liquid Murashige and Skoog medium
      supplemented with 2.5 mg/l kinetin attained a growth index (GI) of 6.06 along
      with the highest asiaticoside content of 3.8 mg/g dry weight on the 35th day of
      the culture cycle. The shoot growth and asiaticoside accumulation were found to
      be influenced by the relative proportions of NH(4)(+)-N:NO(3)(-)-N or Cu(2+)
      concentration in the medium. Asiaticoside content in shoots increased from 5.3 to
      8.9 and 8.7 mg/g dry weight when total nitrogen concentration of 60 mM in the
      control medium was reduced to 50 and 40 mM with a corresponding change in NH(4)
      (+):NO(3)(-) ratio from 20:40 to 20:30 or 20:20, respectively. Total nitrogen
      level higher than 60 mM drastically reduced the asiaticoside concentration in
      these in vitro shoot cultures. Medium devoid of Cu(2+) significantly favored
      higher asiaticoside accumulation in the cultured tissue (7.05 mg/g dry weight)
      along with an improved biomass production (GI = 7.7) when compared with shoots
      reared on the control medium with 0.10 MUM Cu(2+) (GI = 5.8; asiaticoside content
      = 4.4 mg/g dry weight). Carbohydrate enrichment of the medium by increasing the
      sucrose concentration from 3.0 to 5.0 or 7.0% was also beneficial for biomass and
      asiaticoside production with GI = 17.1 and 16.9 and asiaticoside content = 7.2
      and 5.2 mg/g dry weight, respectively, in comparison to control cultures
      maintained on medium containing 3.0% sucrose. The procedure described here
      provides a viable production platform for generating clean and quality material
      from Centella with high bioactive content.

PMID- 21947692
TI  - Granulomatous interstitial nephritis associated with atypical drug-induced
      hypersensitivity syndrome induced by carbamazepine.
AB  - We report the case of a 70-year-old female patient with granulomatous
      interstitial nephritis (GIN) induced by carbamazepine (CBZ). The patient had a 22
      year history of bipolar disorder. Approximately 50 days before admission to our
      hospital, she was switched from valproic acid to 200 mg/day CBZ for mood swings.
      Forty days later, she presented with mild transient platelet depletion and liver
      dysfunction along with a C-reactive protein (CRP) level of 2.65 mg/dL. At that
      time, she discontinued CBZ without consulting the doctor. She subsequently
      developed high fever and a pruritic maculopapular rash. Laboratory tests revealed
      an elevated CRP level (11.98 mg/dL) and serum creatinine (sCr) of 1.6 mg/dL.
      Hence, she was admitted to our hospital, where she showed eosinophilia and
      immunoglobulin suppression. She was diagnosed with atypical drug-induced
      hypersensitivity syndrome (DIHS). All drugs prescribed by the previous doctor
      were discontinued. A lymphocyte transformation test showed CBZ positivity; a
      renal biopsy revealed many granulomatous lesions connected to arterioles, without
      angionecrotic findings. The patient had no history of allergic disorders or
      tuberculosis. Because of psychological instability, we treated her conservatively
      without steroid administration. She had a good recovery except for mild residual
      renal insufficiency (sCr, 1.0 mg/dL). Although granuloma formation has been
      observed in kidney biopsy specimens of rare cases with DIHS, no previous studies
      have reported on the relationship between arterioles and granuloma formation.

PMID- 21947693
TI  - Comparison of throughput times for limited English proficiency patient visits in
      the emergency department between different interpreter modalities.
AB  - Appropriate interpretation is imperative for families with limited English
      proficiency (LEP). We compared throughput times for ED visits involving families
      with LEP based on type of interpretation provided: in-person interpretation,
      remote telephonic interpretation or bilingual providers. This study is a
      secondary analysis of a prospective study of caretaker satisfaction with
      different interpreter modalities. We queried the medical record for event time
      stamps, clinical factors and disposition. The in-person cohort (116 min) had a
      significantly shorter total throughput time than telephonic (141 min) and
      bilingual provider (153 min) cohorts (P < 0.0001), due to a difference in time
      seen by provider to disposition. Time seen by provider to disposition remained
      statistically significantly shorter for the in-person cohort when compared to
      telephonic interpretation when controlling for potential confounders such as
      admission rate (P = 0.006). In-person interpretation significantly decreased ED
      throughput times and may be an important consideration in the choice of
      interpreter modality.

PMID- 21947694
TI  - Silencing of glucose-regulated protein 78 (GRP78) enhances cell migration through
      the upregulation of vimentin in hepatocellular carcinoma cells.
AB  - BACKGROUND: Glucose-regulated protein 78 (GRP78) plays an important role in
      embryonic development and cancer progression. However, there is little
      information regarding the regulation of GRP78 in hepatocellular carcinoma (HCC)
      metastasis. METHODS: We used RNA silencing and cDNA expression vectors to
      manipulate target gene expression in HCC cells. The transwell migration assay and
      xCelligence biosensor system were applied to determine the proliferatory and
      migratory ability of the HCC cells. RESULTS: In this study, we found that GRP78
      silencing enhanced cell migration in both HepJ5 and Mahlavu cells. Overexpressed
      GRP78 in skHep1 cells suppressed the migratory ability. In the insight mechanism
      dissection for GRP78-mediated cancer migration, we found that downregulation of
      GRP78 caused the increase of vimentin expression on HCC cells. Suppressed
      vimentin expression also decreased the migratory ability on HCC, indicating that
      vimentin expression levels modulated the cell migratory ability. CONCLUSION: We
      found that silencing GRP78 in HCC cells may enhance cell migration through the
      increase of vimentin expression.

PMID- 21947695
TI  - Comparative assessment of the safety and effectiveness of radiofrequency ablation
      among elderly medicare beneficiaries with hepatocellular carcinoma.
AB  - BACKGROUND: Radiofrequency ablation (RFA) use among patients with hepatocellular
      carcinoma (HCC) has increased dramatically over the last decade, but assessments
      outside specialized centers are lacking. This population-based study was intended
      to evaluate the safety and effectiveness of RFA when used to treat HCC. METHODS:
      A cohort study of HCC patients (diagnosed 2002-2005) was performed using linked
      Surveillance, Epidemiology, and End Results (SEER)-Medicare data. Early (<=90
      day) mortality and readmission as well as survival among patients undergoing RFA,
      resection, or no treatment were compared using multivariate and propensity score
      adjusted Poisson and Cox regression models. RESULTS: Of 2631 patients (mean age
      76.1+/-6.1 years, 65.9% male), 16% underwent RFA (49.6%) or resection (50.4%).
      Early mortality (13.6 vs. 18.7%, P=.16) and readmission (34.5 vs. 32.1%, P=.60)
      rates were similar among RFA and resection patients. The 1-year survival after
      RFA and resection was similar (72.2 vs. 79.7%, P=.18), but beyond 3 years there
      was a survival benefit among patients undergoing resection (39.2 vs. 58.0%,
      P<.001). Patients treated with RFA as a sole therapeutic intervention in the 1st
      year had a similar hazard of death compared with untreated patients (hazard ratio
      [HR] 0.84, 95% confidence interval [95% CI] 0.54-1.33). CONCLUSIONS: In the
      general community, patients treated with RFA have a similar risk of early adverse
      events compared with those treated with resection with no clear survival benefit
      when used as a sole intervention. Although RFA has been described as a safe and
      effective treatment for HCC at specialized centers, this experience may not
      extrapolate to the general community and requires further evaluation.

PMID- 21947696
TI  - Prognosis of esophageal squamous cell carcinoma in patients positive for human
      epidermal growth factor receptor family can be improved by initial chemotherapy
      with docetaxel, fluorouracil, and cisplatin.
AB  - BACKGROUND: The human epidermal growth factor receptor (HER) family, Ki-67 and
      p53 are important biomarkers for several malignancies. However, few studies have
      examined the role of these in prognosis and therapeutic sensitivity of esophageal
      squamous cell carcinoma (ESCC). The efficacy of triple-drug combination therapy
      with docetaxel, fluorouracil and cisplatin has recently been expected for ESCC.
      METHODS: Subjects comprised 142 patients with ESCC who underwent operation (OP
      group, n = 54), neoadjuvant chemotherapy with docetaxel, fluorouracil, and
      cisplatin (DFP therapy) followed by operation (NAC group, n = 37) or initial
      systemic DFP therapy (CT group, n = 51) between January 2004 and December 2010.
      Immunohistochemical expressions of epidermal growth factor receptor (EGFR), HER2,
      HER3, Ki-67, and p53 were evaluated and compared with prognosis and sensitivity
      to DFP therapy. RESULTS: Positive correlations existed between EGFR, HER2, and
      HER3 expressions. In the OP group, EGFR was independently associated with
      postoperative recurrence in multivariate analysis (P = .036). In the NAC group,
      EGFR correlated with pathological response to DFP therapy (P = .004). In the CT
      group, EGFR, HER2, and HER3 correlated with clinical response to DFP therapy and
      EGFR was independently associated with favorable prognosis in multivariate
      analysis (P = .022). CONCLUSION: EGFR represents a predictor of postoperative
      recurrence and sensitivity to triple-drug combination therapy including a taxane.
      EGFR-positive patients may show improved prognosis with taxane combination
      chemotherapy and molecular targeted therapy for HER family members.

PMID- 21947697
TI  - Significance of pathologic response to preoperative therapy in pancreatic cancer.
AB  - BACKGROUND: Pathologic response to preoperative therapy is increasingly
      recognized as an important prognostic factor in solid tumors. The impact of
      pathologic response on survival in pancreatic adenocarcinoma is not well
      established. METHODS: Data on 135 consecutive patients treated with
      chemoradiation followed by pancreatectomy for adenocarcinoma of the pancreatic
      head and/or body between July 1987 and May 2009 were reviewed. Histopathologic
      examination was performed in 107 patients to determine pathologic response,
      defined as minor (<50% fibrosis relative to residual neoplastic cells), partial
      (50-94% fibrosis), or major (95-100% fibrosis). RESULTS: Minor, partial, and
      major pathologic response rates were 17% (n = 18), 64% (n = 68), and 19% (n =
      21), including a 7% (n = 8) complete pathologic response rate. Pathologic
      response correlated with R0 resection (P = 0.019), negative lymph nodes (P =
      0.006), and smaller tumor size (P = 0.001). Median survival rates by pathologic
      response were as follows: 17 months [95% confidence interval (CI), 0-36 months]
      for minor response, 20 months (95% CI, 17-23 months) for partial response, and 66
      months (95% CI, 8-124 months) for major response (minor versus partial response,
      P = not significant; partial versus major response, P < 0.001). On multivariate
      analysis, major pathologic response was the only factor significantly associated
      with improved survival (P = 0.025; hazard ratio, 2.26). CONCLUSIONS: Major
      pathologic response to preoperative therapy occurs in a minority of patients with
      pancreatic adenocarcinoma and is independently associated with prolonged
      survival.

PMID- 21947698
TI  - Race and health disparities in patient refusal of surgery for early-stage non
      small cell lung cancer: a SEER cohort study.
AB  - INTRODUCTION: Several factors, including race, age, stage, comorbid conditions,
      social support, and socioeconomic status, have been linked to the likelihood of a
      patient having surgery for early-stage non-small cell lung cancer (NSCLC). The
      aim of the present study is to determine the influence of race and health
      disparities on refusal of recommended potentially curative surgery. METHODS: The
      Surveillance, Epidemiology, and End Results (SEER) database was used to create a
      cohort of 62,514 patients diagnosed with stages I and II NSCLC between 1988 and
      2002, of whom 51,938 were recommended for surgery. The outcome variable was
      refusal of recommended surgical treatment, while race was the key predictor
      variable. Potential confounders were adjusted for in the hierarchical generalized
      logistic regression analysis. RESULTS: A majority was White (86%) and underwent
      surgery (81%). About 2% of Blacks (n = 109), 1.4% of Whites (n = 756), and 2.8%
      of "other" race individuals (n = 96) refused surgery. In the multivariable
      adjusted model, Blacks [odds ratio (OR) 1.95, 95% confidence interval (CI) 1.5,
      2.3, P < 0.001] and those of "other" race (OR 2.03, 95% CI 1.5, 2.5, P < 0.001)
      had greater odds of refusing surgery than did Whites. Increasing age, male gender
      (OR 1.17, P = 0.031), and being unmarried (OR 2.1, P < 0.001) were other factors
      associated with higher odds of refusal. Significant county variations were also
      noted in refusal of surgery. CONCLUSIONS: Blacks and "other" races are more
      likely to refuse recommended surgery for early-stage NSCLC compared with Whites.
      Future studies should focus on exploring potential reasons for refusal and
      developing communication interventions.

PMID- 21947699
TI  - Significance of pathologic response to preoperative therapy in pancreatic cancer:
      the future ain't what it used to be.

PMID- 21947700
TI  - Cost of medication errors in rheumatic patients in Mexico.
AB  - This study aims to measure the frequency of medication error (ME) in rheumatology
      outpatients of the Social Security System (SS) in Mexico and to measure the costs
      by comparing the days lost at work as direct consequence of the medication error
      against the theoretical cost of no error in the process. A prospective 6-month
      survey was conducted in a reference hospital in Guadalajara, Mexico. ME was
      defined as any discrepancy between the prescription and medicine taken by
      patients. The origin of the discrepancy was identified and registered. We present
      381 patients: 292 with rheumatoid arthritis, 57 with ankylosing spondylitis, and
      32 with systemic lupus erythematosus. One hundred twenty seven (33%) had
      medication errors. Ninety eight (77%) got worse in their condition due to ME.
      Forty percent of MEs were due to patients' decisions, 41% to a lack of
      availability of medication which should have been provided by SS, and 18% to a
      non-justified medical decision by primary-care providers. Patients lost in
      average 3 working days each month because of the ME. The cost of ME is high. In
      the case analyzed, opportune access to treatment represents a lower cost for the
      system, but it represents a significant loss of days at work each month. ME is a
      signal of a system failure. Inter-professional teamwork is needed to perfect the
      system.

PMID- 21947701
TI  - Adaptation and validation of the Osteoarthritis Knee and Hip Quality of Life
      (OAKHQOL) questionnaire for use in patients with osteoarthritis in Spain.
AB  - This study aims to adapt and validate the Spanish version of the Osteoarthritis
      Knee and Hip Quality of Life (OAKHQOL) questionnaire. The OAKHQOL was adapted
      into Spanish using a forward-backward translation methodology. The Spanish
      version was then validated in a prospective, mixed-design study of 759 patients
      with hip or knee osteoarthritis (OA). Patients completed the OAKHQOL, Short Form
      36 (SF-36), Western Ontario and McMaster Universities Osteoarthritis Index, and
      the EQ-5D. The internal consistency was evaluated using Cronbach's alpha.
      Convergent validity was assessed by examining correlations between the OAKHQOL
      and other patient-reported instruments; known groups' validity was assessed by
      determining the capacity of the OAKHQOL to discriminate between patients with
      different levels of disease severity measured using the Lequesne Index. Test
      retest reliability was evaluated by calculating the intraclass correlation
      coefficient (ICC) for all OAKHQOL domains in 409 stable patients with OA.
      Responsiveness was evaluated by calculating effect sizes among 129 patients
      undergoing hip or knee replacement. Cronbach's alpha for the five domains of the
      OAKHQOL ranged from 0.60 to 0.93 while ICCs ranged from 0.75 to 0.81 for all
      domains except the two social domains. Statistically significant differences (p <
      0.001) were observed between patients with different degrees of disease severity
      on all domains except "social support". The instrument showed convergent validity
      among hypothesized domains (p < 0.001). Results of the study supported that the
      Spanish version OAKHQOL questionnaire was a valid instrument to measure health
      related quality of life in patients with OA of the lower limb.

PMID- 21947702
TI  - Column bioleaching of low-grade mining ore containing high level of smithsonite,
      talc, sphaerocobaltite and azurite.
AB  - Present work describes the bioleaching potential of metals from low-grade mining
      ore containing smithsonite, sphaerocobaltite, azurite and talc as main gangue
      minerals with adapted consortium of Sulfobacillus thermosulfidooxidans strain-RDB
      and Thermoplasma acidophilum. Bioleaching potential improved markedly by added
      energy source, acid preleaching and adaptation of microbial consortium with mixed
      metal ions. During whole leaching period including acid preleaching stage of 960
      h and bioleaching stage of 212 days about 76% Co, 70% Zn, 84% Cu, 72% Ni and 63%
      Fe leached out.

PMID- 21947703
TI  - Physiological studies on microalgal culture additives to optimize growth rate and
      oil content.
AB  - Insulin, in nature, has a stimulatory effect on microorganisms. These effects
      include the acceleration of sugar metabolism, triacylglycerol anabolism, growth
      rate, and formation of oils. We also observed that insulin may cause indirect
      activation of triacylglycerol lipase by forcing the cell to permanently require
      an energy source. Thus, cells can consume all of their accumulated internal fuel
      sources such as lipids, proteins, and carbohydrates. After studying the effects
      of using two types of insulin (Humulin 70/30, and human insulin expressed in
      yeast) at different concentrations on microalgae (Chlorella sp.), we found that
      with certain concentrations of insulin (1:3.3 ml unit Humulin 70/30 per ml; 1:2.6
      ml unit yeast insulin per ml), there was an increase in algal growth rate and
      decrease in cell size. We therefore studied the effect of insulin under
      conditions of lipase inhibition by Triton WR 1339 (Tyloxapol), which was used at
      different concentrations with and without insulin. We found strong regression in
      the growth rate with increasing Triton concentrations. However, we also observed
      that the cell size under the effect of Triton and Triton-insulin was larger than
      the cell size under the effect of insulin alone, and also larger than for control
      cells. Also, the oil content of the Triton-insulin cells was higher than those of
      the control cells or the cells under the effect of insulin alone.

PMID- 21947704
TI  - Modeling the system dynamics for nutrient removal in an innovative septic tank
      media filter.
AB  - A next generation septic tank media filter to replace or enhance the current on
      site wastewater treatment drainfields was proposed in this study. Unit operation
      with known treatment efficiencies, flow pattern identification, and system
      dynamics modeling was cohesively concatenated in order to prove the concept of a
      newly developed media filter. A multicompartmental model addressing system
      dynamics and feedbacks based on our assumed microbiological processes accounting
      for aerobic, anoxic, and anaerobic conditions in the media filter was constructed
      and calibrated with the aid of in situ measurements and the understanding of the
      flow patterns. Such a calibrated system dynamics model was then applied for a
      sensitivity analysis under changing inflow conditions based on the rates of
      nitrification and denitrification characterized through the field-scale testing.
      This advancement may contribute to design such a drainfield media filter in
      household septic tank systems in the future.

PMID- 21947705
TI  - Dynamics of regulatory T cells and plasmacytoid dendritic cells as immune markers
      for virological response in pegylated interferon-alpha and ribavirin therapy for
      chronic hepatitis C patients.
AB  - BACKGROUND: For the treatment of chronic hepatitis C, a combination of pegylated
      interferon-alpha (PEG-IFNalpha) and ribavirin has been widely used as a standard
      of care. Enhancement of immune response against hepatitis C virus (HCV) is known
      to be involved in the efficacy of the combination therapy. Our aim was to
      elucidate whether or not the frequency or function of blood cells is related to
      the outcome of the therapy. METHODS: Sixty-seven chronic hepatitis C patients
      with high viral load of HCV genotype 1 infection who underwent 48 weeks of PEG
      IFNalpha2b and ribavirin therapy were examined. During the treatment, frequencies
      of myeloid or plasmacytoid dendritic cells, Th1, Th2 cells, NK cells, and
      regulatory T cells were phenotypically determined. RESULTS: Among the patients
      enrolled, 29 showed a sustained virological response (SVR), 18 a transient
      response (TR) and 17 no response (NR). The clinical and immunological markers
      were compared between the SVR and non-SVR patients, including TR and NR. Based on
      clinical, histological, immunological parameters, and cumulative dosage of PEG
      IFNalpha2b and ribavirin, multivariate analyses revealed that higher platelet
      counts and higher regulatory T cell frequency at week 12 are indicative of SVR.
      Even in patients who attained complete early virological response at week 12,
      multivariate analyses disclosed that higher platelet counts and higher
      plasmacytoid dendritic cell frequency are indicative of SVR. CONCLUSIONS: In PEG
      IFNalpha and ribavirin combination therapy for chronic hepatitis C patients, the
      increments of regulatory T cells and plasmacytoid dendritic cell frequency are
      independently related to favorable virological response to the therapy.

PMID- 21947706
TI  - Long-term administration of PPI reduces treatment failures after esophageal
      variceal band ligation: a randomized, controlled trial.
AB  - BACKGROUND AND PURPOSE: Elective esophageal variceal ligation (EVL) is performed
      to decrease the risk of variceal hemorrhage. EVL is associated with adverse
      effects, including post-ligated bleeding, chest pain, and dysphagia. Proton pump
      inhibitors (PPIs) are the most potent pharmacological agents for inhibition of
      gastric acid secretion. However, the long-term effect of PPIs after EVL remains
      unclear. The aim of this study was to assess the efficacy of rabeprazole, a PPI,
      after variceal eradication by EVL. METHODS: We performed a randomized, controlled
      trial in Kitasato University East Hospital. The primary endpoint was treatment
      failure, defined as variceal hemorrhage or severe medical complications. Between
      July 2007 and September 2010, 43 patients were randomized into this study and
      followed up until September 2010. RESULTS: Twenty-one patients in the rabeprazole
      arm received 10 mg rabeprazole daily after EVL, and 22 patients in the control
      received no antisecretory treatment from the same stage. Baseline characteristics
      did not differ between the groups (median Child-Pugh score, 6; median age, 62
      years; median follow-up, 18.7 months). The trial was stopped early after an
      interim analysis showed that the risk of bleeding and failure of rabeprazole
      treatment was lower than that of no antisecretory treatment with the log-rank
      test showing a significant difference between the groups (P = 0.007) and a hazard
      ratio of 0.098 [95% confidence interval, 0.012-0.79 (P = 0.029)]. CONCLUSIONS:
      Long-term administration of PPIs reduced the risk of treatment failure after EVL.
      Acid suppression therapy should also be considered as a treatment option after
      EVL.

PMID- 21947707
TI  - Leptin and leptin receptor genes in relation to premenopausal breast cancer
      incidence and grade in Caucasian women.
AB  - Body mass is inversely related to breast cancer risk among premenopausal women.
      Leptin, an essential cytokine regulating food intake, energy expenditure,
      glucose, and fat metabolism may be part of the mechanistic pathway. We
      investigated 50 tagging and candidate SNPs in the leptin (LEP) and leptin
      receptor (LEPR) genes for associations with premenopausal breast cancer incidence
      using 405 cases and 810 controls nested within the Nurses' Health Study II. We
      also examined associations between these SNPs and circulating leptin (among 910
      women) and breast cancer grade (among 267 patients). Permutation tests were
      performed to adjust for multiple testing. We did not detect a significant
      association between SNPs in the LEP or LEPR gene and either breast cancer
      incidence or plasma leptin levels. Among cases, 14 SNPs of the LEPR gene were
      significantly associated with cancer grade, and rs1137101 (Q223R) survived
      multiple testing adjustment (adjusted P = 0.04). The G carriers of rs1137101 were
      more likely to have poorly differentiated than well-differentiated cancers. Our
      data suggest that common genetic variation in the LEP or LEPR gene has no strong
      association with premenopausal breast cancer risk. The LEPR gene might be
      associated with breast cancer grade.

PMID- 21947708
TI  - Is knowledge translation adequate? A quality assurance study of staging
      investigations in early stage breast cancer patients.
AB  - After primary surgery, patients diagnosed with early stage breast cancer undergo
      radiological investigations based on pathologic stage of disease to rule out
      distant metastases. Published guidelines can aid clinicians in determining which
      tests are appropriate based on stage of disease. We wished to assess the
      consistency of radiological staging in an academic community oncology setting
      with standard guidelines and to determine the overall impact of non-adherence to
      these guidelines. A retrospective cohort study was conducted for new breast
      cancer patients seen at a single institution between January 2009 and April 2010.
      Patients were included if initial diagnosis and primary surgery was at this
      institution. Pathologic stage and radiological tests completed were recorded. A
      literature review was performed and the results were compared with those from
      this study to determine overall adherence rates. Subsequently, a cost analysis
      was performed to determine the financial impact at this centre. 231 patients met
      eligibility criteria for inclusion in this study. A large proportion of patients
      were over-staged with 129 patients (55%) undergoing unnecessary investigations
      according to guidelines. Specifically, 59% of stage I patients and 58% of stage
      II patients were over-investigated. Distant metastases at the time of diagnosis
      were found in three patients, all of whom had stage III disease (1.3%). The
      literature reviewed revealed similar non-adherence rates in other centres. The
      estimated cost of such non-adherence is in the range of $78 (CDN) per new early
      stage breast cancer patient seen at this centre. This oncology centre has a low
      adherence to practice guidelines for staging investigations in breast cancer
      patients, with 55% of patients undergoing unnecessary tests. Very few patients
      had metastases at diagnosis, and all had pathological stage III disease. Efforts
      may need to focus on improving knowledge translation across clinical oncology
      settings to increase guideline adherence.

PMID- 21947709
TI  - Brief report: An exploratory study of lexical skills in bilingual children with
      autism spectrum disorder.
AB  - Studying lexical diversity in bilingual children with autism spectrum disorders
      (ASD) can contribute important information to our understanding of language
      development in this diverse population. In this exploratory study, lexical
      comprehension and production and overall language skills were investigated in 14
      English-Chinese bilingual and 14 English monolingual preschool-age children with
      ASD. Results indicated that both groups had equivalent scores on all but one
      measure of language and vocabulary, including English production vocabulary,
      conceptual production vocabulary, and vocabulary comprehension. When comparing
      the two languages of bilingual participants, there were no significant
      differences in production vocabulary size or vocabulary comprehension scores. The
      results provide evidence that bilingual English-Chinese preschool-age children
      with ASD have the capacity to function successfully as bilinguals.

PMID- 21947710
TI  - Gluconacetobacter hansenii subsp. nov., a high-yield bacterial cellulose
      producing strain induced by high hydrostatic pressure.
AB  - Strain M(438), deposited as CGMCC3917 and isolated from inoculums of bacterial
      cellulose (BC) producing strain screened in homemade vinegar and then induced by
      high hydrostatic pressure treatment (HHP), has strong ability to produce BC more
      than three times as that of its initial strain. It is the highest yield BC
      producing strain ever reported. In this paper, M(438) was identidied as
      Gluconacetobacter hansenii subsp. nov. on the basis of the results obtained by
      examining it phylogenetically, phenotypically, and physiologically-biochemically.
      Furthermore, the genetic diversity of strain M(438) and its initial strain was
      examined by amplified fragment length polymorphism. The results indicated that
      strain M(438) was a deletion mutant induced by HHP, and the only deleted sequence
      showed 99% identity with 24,917-24,723 bp in the genome sequence of Ga. hansenii
      ATCC23769, and the complement gene sequence was at 24,699-25,019 bp with local
      tag GXY_15142, which codes small multidrug resistance (SMR) protein. It can be
      inferred that SMR might be related to inhibiting BC production to a certain
      extent.

PMID- 21947711
TI  - Construction of copper removing bacteria through the integration of two-component
      system and cell surface display.
AB  - Synthetic biological systems are becoming more and more feasible for commercial
      and medical purposes through the genetic engineering of several components. The
      simple assembly of a genetic circuit was shown to stimulate the removal of copper
      by bacteria through the engineering of a two-component system. The CusSR two
      component systems is a regulator of Escherichia coli copper homeostatic system.
      In this system, genetic circuits of CusSR were fused to a cell surface display
      system for metal adsorption; this system is suitable for the display of a copper
      binding peptide through outer membrane protein C (OmpC). E. coli ompC codes for
      an outer membrane pore protein (porin) are induced at high osmolarity and
      temperature, which can also be used as an anchoring motif to accept the passenger
      proteins. The bacteria that produce the chimeric OmpC containing the copper
      binding peptide adsorbed maximum concentrations of 92.2 MUmol of Cu(2+)/gram dry
      weight of bacterial cells. This synthetic bacterial system senses the specific
      heavy metal and activates a cell surface display system that acts to remove the
      metal.

PMID- 21947712
TI  - Activity and stability of chloroperoxidase in the presence of small quantities of
      polysaccharides: a catalytically favorable conformation was induced.
AB  - Chloroperoxidase (CPO) is thought to be the most versatile heme-containing enzyme
      with enormous applications in organic synthesis, biotransformation,
      pharmaceutical production, and detoxification of environmental pollutants. Any
      improvement in the stability of this enzyme will greatly enhance its application
      in the mentioned areas. In the present study, the effects of three
      polysaccharides (soluble starch, beta-cyclodextrin, and dextrin) on the stability
      of CPO at elevated temperatures (20, 30, 35, 40, and 50  degrees C) or in aqueous
      organic solvents media (methanol, dioxane, DMSO, and DMF) were investigated. An
      improved catalytic performance of CPO was observed in the presence of a small
      amount of the three polysaccharides, where dextrin provided the most effective
      promotion. The changes of enzyme structure and microenvironment around heme in
      the presence of additives were studied by fluorescence, circular dichroism, and
      UV-vis spectra analyses, as well as kinetic parameters measurement. A
      catalytically favorable structure of CPO was induced, including the strengthening
      of the alpha-helix structure and more exposure of heme for easy access of the
      substrate, resulting in an increase of catalytic turnover frequency (k (cat)) and
      the improvement of affinity and selectivity of CPO to substrate. The results
      revealed that the introduction of trace soluble starch, beta-cyclodextrin, and
      dextrin (<10 MUmol/L) in reaction media was an effective strategy for the
      enhancement of the thermodynamic and the operational stability of the enzyme,
      which are promising in view of the industrial applications of this versatile
      biological catalyst.

PMID- 21947713
TI  - Multienzymatic sucrose conversion into fructose and gluconic acid through fed
      batch and membrane-continuous processes.
AB  - Multienzymatic conversion of sucrose into fructose and gluconic acid was studied
      through fed-batch and continuous (in a membrane reactor) processes. The law of
      substrate addition (sucrose or glucose) for the fed-batch process which led to a
      yield superior to 80% was the decreasing linear type, whose feeding rate (phi;
      L/h) was calculated through the equation: phi = phi(o) - k.t, where phi(o)
      (initial feeding rate, L/h), k (linear addition constant, L/h (2)), and t
      (reaction time, h). In the continuous process, the yield of conversion of sucrose
      (Y) was superior to 70% under the following conditions: dilution rate = 0.33 h(
      1), total duration of 15 h, pH 5.0, 37  degrees C and initial sucrose
      concentration of 64 g/L (Y = 92%), 100 g/L (Y = 83%), or 150 g/L (Y = 76%).

PMID- 21947714
TI  - Sulfate reduction in groundwater: characterization and applications for
      remediation.
AB  - Sulfate is ubiquitous in groundwater, with both natural and anthropogenic
      sources. Sulfate reduction reactions play a significant role in mediating redox
      conditions and biogeochemical processes for subsurface systems. They also serve
      as the basis for innovative in situ methods for groundwater remediation. An
      overview of sulfate reduction in subsurface environments is provided, along with
      a brief discussion of characterization methods and applications for addressing
      acid mine drainage. We then focus on two innovative, in situ methods for
      remediating sulfate-contaminated groundwater, the use of zero-valent iron and the
      addition of electron-donor substrates. The advantages and limitations associated
      with the methods are discussed, with examples of prior applications.

PMID- 21947715
TI  - Overview of serological-specific IgE antibody testing in children.
AB  - Allergic diseases are among the most common chronic conditions in the pediatric
      population. Allergy diagnostic testing is an important part of the
      evaluation/management of allergic patients because the history may not be precise
      enough to identify the specific allergen sensitivity. In addition to providing
      information about specific sensitivities, allergy diagnostic tests have some
      predictive value in terms of future risk of developing an allergic condition and
      the severity/persistence of the allergic disease. The two most commonly used
      methods of confirming allergen sensitization are skin testing and measurement of
      serum-specific IgE. Both methods have similar diagnostic value in terms of
      sensitivity and specificity, with both parameters varying with the clinical
      scenario and allergen tested. Currently, there are three US Food and Drug
      Administration-cleared, serum-specific IgE assays used in the United States. The
      three assays report comparable analytic sensitivity, with the coefficients of
      variation of the precision, reproducibility, and linearity being less than 15%.
      However, comparative studies have demonstrated significant inter-assay
      variability, suggesting that they detect different populations of IgE antibody in
      human sera or do not measure the same antibodies with the same efficiency.
      Current specific IgE assays utilize allergen extract reagents. Testing with these
      reagents may identify sensitivity to clinically irrelevant allergens. This
      diagnostic limitation has spurred the development of molecular diagnostic tests,
      also referred to as component-resolved diagnostics, which utilize purified native
      or recombinant allergens to detect IgE sensitivity to individual allergen
      molecules. These advancements in serum IgE testing may enhance the precision of
      allergy diagnostic testing, which may decrease the need for oral food challenges
      and improve the specificity of allergen immunotherapy.

PMID- 21947716
TI  - Efficient synthesis and free-radical scavenging capacity of new 2,4-substituted
      tetrahydroquinolines prepared via BiCl3-catalyzed three-component Povarov
      reaction, using N-vinylamides.
AB  - Efficient synthesis of new structurally different 2-(het)aryl-4-amidyl
      substituted tetrahydroquinolines 8-29 is reported. The synthesis based on BiCl(3)
      catalyzed three-component Povarov reaction between anilines, (het)aryl aldehydes
      and enamides offers a fast, safe, and cheap way for efficient tetrahydroquinoline
      libraries construction. Using N-vinylamides (N-vinylpyrrolidin-2-one and N
      vinylacetamide) in this reaction, it was possible to obtain two series of
      different cis tetrahydroquinolines with antioxidant properties. Among 14 tested
      compounds, 7 tetrahydroquinolines revealed a prominent anti-radical capacity,
      equal or higher than that of the commercial antioxidants. Being the most active
      molecule, the N-[2-(alpha-furanyl)-6-methoxy-1,2,3,4-tetrahydroquinolin-4-yl]
      acetamide 21 was ca. 2.2-fold more potent than the well-known antioxidant,
      vitamin E (alpha-tocopherol).

PMID- 21947717
TI  - A case of unsuccessful treatment of heparin-induced thrombocytopenia (HIT) with
      fondaparinux.
AB  - Heparin-induced thrombocytopenia (HIT) is a rare immune-mediated complication
      associated with unfractionated heparin and to a lesser extent with low-molecular
      weight heparins. The American College of Chest Physicians recommends treating
      patients with suspected HIT with a non-heparin product regardless if thrombosis
      is present. The direct thrombin inhibitors are the preferred agents for the
      treatment of acute HIT (lepirudin, argatroban [Grade 1C]). Fondaparinux is also
      suggested as an alternative with a lower level of evidence (Grade 2C). The
      evidence supporting the use of fondaparinux in the treatment of HIT is limited,
      but the evidence of fondaparinux causing HIT is even less. We present a case of a
      patient who developed complications with fondaparinux when used in the acute
      setting of HIT.

PMID- 21947718
TI  - Corticosteroids or non-corticosteroids: a fresh perspective on alcoholic
      hepatitis treatment.
AB  - BACKGROUND: Alcoholic hepatitis (AH) is a necrotizing inflammatory process caused
      by alcoholic liver injury. It carries a significant short-term mortality. The
      management of AH is challenging. Although corticosteroids have been demonstrated
      to exert anti-inflammatory and antifibrotic effects, their efficacy for the
      treatment of AH remains debatable. DATA SOURCES: A literature search was
      performed of MEDLINE, ScienceDirect, SpringerLink and Wiley InterScience using
      the keywords "alcoholic hepatitis", "alcoholic liver disease", and
      "corticosteroids". The available data reported in the relevant literature were
      analyzed. RESULTS: More than 17 controlled trials and at least 13 meta-analyses
      have reported the efficacy of corticosteroids in the treatment of AH in the past
      40 years. Many were poorly designed and used different inclusion/exclusion
      criteria, making it difficult to reach a consensus. In this review, we summarized
      all the controversial data in the past decade and analyzed the potential causes
      for the varying therapeutic effects of corticosteroids in AH. The focus of the
      controversy has changed from "whether steroids are beneficial or harmful for AH
      patients" to "how to accurately identify responders to steroids early and
      rationalize corticosteroid treatment". An early response to glucocorticoids, as
      determined by calculating the Lille score after 7 days of treatment, has been
      shown to be a clinically useful indicator. Moreover, down-regulation of steroid
      sensitivity, risk of infection, and a rational therapeutic strategy of
      corticosteroids in AH patients are all crucial for therapeutic effect.
      CONCLUSIONS: An early and accurate determination of steroid sensitivity is
      important. Besides, we need to overcome the down-regulation of steroid
      sensitivity, reduce the infection risk and rationalize the therapeutic strategy
      of corticosteroids. A fresh perspective is needed on the use of corticosteroids
      in AH patients.

PMID- 21947719
TI  - Autoimmune pancreatitis versus pancreatic cancer: a comprehensive review with
      emphasis on differential diagnosis.
AB  - BACKGROUND: Autoimmune pancreatitis (AIP) is a rare form of chronic pancreatitis
      with a discrete pathophysiology, occasional diagnostic radiological findings, and
      characteristic histological features. Its etiology and pathogenesis are still
      under investigation, especially during the last decade. Another aspect of
      interest is the attempt to establish specific criteria for the differential
      diagnosis between autoimmune pancreatitis and pancreatic cancer, entities that
      are frequently indistinguishable. DATA SOURCES: An extensive search of the PubMed
      database was performed with emphasis on articles about the differential diagnosis
      between autoimmune pancreatitis and pancreatic cancer up to the present. RESULTS:
      The most interesting outcome of recent research is the theory that autoimmune
      pancreatitis and its various extra-pancreatic manifestations represent a systemic
      fibro-inflammatory process called IgG4-related systemic disease. The diagnostic
      criteria proposed by the Japanese Pancreatic Society, the more expanded HISORt
      criteria, the new definitions of histological types, and the new guidelines of
      the International Association of Pancreatology help to establish the diagnosis of
      the disease types. CONCLUSION: The valuable help of the proposed criteria for the
      differential diagnosis between autoimmune pancreatitis and pancreatic cancer may
      lead to avoidance of pointless surgical treatments and increased patient
      morbidity.

PMID- 21947720
TI  - Living donor liver hilar variations: surgical approaches and implications.
AB  - BACKGROUND: Varied vascular and biliary anatomies are common in the liver. Living
      donor hepatectomy requires precise recognition of the hilar anatomy. This study
      was undertaken to study donor vascular and biliary tract variations, surgical
      approaches and implications in living liver transplant patients. METHODS: Two
      hundred living donor liver transplantations were performed at our institution
      between 2004 and 2009. All donors were evaluated by volumetric computerized
      tomography (CT), CT angiography and magnetic resonance cholangiography in the
      preoperative period. Intraoperative ultrasonography and cholangiography were
      carried out. Arterial, portal and biliary anatomies were classified according to
      the Michels, Cheng and Huang criteria. RESULTS: Classical hepatic arterial
      anatomy was observed in 129 (64.5%) of the 200 donors. Fifteen percent of the
      donors had variation in the portal vein. Normal biliary anatomy was found in 126
      (63%) donors, and biliary tract variation in 70% of donors with portal vein
      variations. In recipients with single duct biliary anastomosis, 16 (14.4%)
      developed biliary leak, and 9 (8.1%) developed biliary stricture; however more
      than one biliary anastomosis increased recipient biliary complications. Donor
      vascular variations did not increase recipient vascular complications. Variant
      anatomy was not associated with an increase in donor morbidity. CONCLUSIONS:
      Living donor liver transplantation provides information about variant hilar
      anatomy. The success of the procedure depends on a careful approach to anatomical
      variations. When the deceased donor supply is inadequate, living donor
      transplantation is a life-saving alternative and is safe for the donor and
      recipient, even if the donor has variant hilar anatomy.

PMID- 21947721
TI  - Evaluation outcomes of donors in living donor liver transplantation: a single
      center analysis of 132 donors.
AB  - BACKGROUND: Donor safety has always been a major concern, and potential risk to
      the donor must be balanced against recipient benefit. However, lack of a
      standardized and uniform evaluation of perioperative complications is a serious
      limitation of the evaluation of donor morbidity. This study was designed to
      evaluate the outcomes of donors in adult living donor liver transplantation
      (LDLT) using the newer Clavien classification system in a single center in China.
      METHODS: We prospectively analyzed the outcomes of 132 consecutive living liver
      donors from 2005 to 2008 using the newer Clavien classification system. The
      preoperative, intraoperative and postoperative data of the donors were collected
      and analyzed. Ordinal regression was used to analyze the ordered grades of
      complications. RESULTS: Ninety-four (71.2%) of the donors developed postoperative
      complications of grade I (n=45, 34.1%), grade II (n=39, 29.5%) and grade III
      (n=10, 7.6%). There was no death or grade IV morbidity. Hepatic functional
      impairment and pleural effusion were the most frequent morbidities for living
      donors. Fifty-three donors (40.1%) developed hepatic functional impairment of
      grade I (n=40, 31.1%) and grade II (n=13, 10.0%). The ICU stay (7.8+/-1.8 days)
      and length of hospital stay (17.7+/-4.6 days) were significantly longer in donors
      with grade III than others. Furthermore, ordinal logistic regression revealed
      that donor's older age (>40 years) and right hepatectomy were associated with
      morbidity. In addition, only preoperative total bilirubin (within the normal
      range) and postoperative nadir serum phosphorus were independently associated
      with hepatic functional impairment. The receiver operator characteristic curve
      revealed that preoperative total bilirubin >18.0 MUmol/L and postoperative nadir
      of serum phosphorus <1 mg/dL may lead to more severe hepatic functional
      impairment. CONCLUSIONS: Despite the fact that donors are relatively safe to
      undergo hepatectomy, many living donors still experience postoperative morbidity.
      Meticulous technical and preoperative donor evaluation and treatment are sure to
      reduce the incidence of complications.

PMID- 21947722
TI  - Protective effect of probiotics on intestinal barrier function in malnourished
      rats after liver transplantation.
AB  - BACKGROUND: Most patients waiting for liver transplantation have end-stage liver
      diseases with malnutrition, which is prone to induce intestinal barrier
      dysfunction after liver transplantation. We aimed to study the effect of
      probiotics on intestinal barrier function in malnourished rats following liver
      transplantation with long-term antibiotics. METHODS: Twelve Lewis rats were
      selected as donors. Twelve BN rats, which served as recipients, were subjected to
      malnutrition by semi-starvation for 4-5 weeks. They were randomly divided into
      two groups: a control group which received phosphate-buffered saline and a
      probiotics group which received Bifidobacterium and Lactobacillus. All recipients
      were injected with intramuscular imipenem and subcutaneous cyclosporine A.
      Furthermore, six normal BN rats without any drugs or operations served as a
      normal group. Eight days after operation, all rats were sacrificed for
      examination of the following parameters: serum levels of endotoxin and TNF-alpha,
      bacterial translocation, intestinal microflora, ileocecal sIgA, lymphocyte
      numbers, and phenotypes (CD4, CD8, alphabetaTCR, gammadeltaTCR) of Peyer's
      patches. RESULTS: In recipients subjected to malnutrition, weight decreased by
      20% and they survived until 8 days after operation. Compared with the normal
      group, all recipients on postoperative day 8 showed increased levels of serum
      endotoxin and TNF-alpha as well as increased counts of translocated bacteria.
      Meanwhile, there were decreases in counts of Bifidobacterium and Lactobacillus in
      the ileocecum, sIgA concentration, and lymphocytes of Peyer's patches. Moreover,
      partial alteration in lymphocyte phenotypes was evidenced by elevated ratios of
      CD8+ and gammadeltaTCR+ lymphocytes. In contrast, compared to the control group,
      supplementation with probiotics reduced the levels of serum endotoxin, TNF-alpha
      and bacterial translocation, increased the counts of Bifidobacterium and
      Lactobacillus, the concentration of sIgA and lymphocytes of Peyer's patches, and
      also slightly restored the alteration of lymphocyte phenotypes. CONCLUSION:
      Supplementation with probiotics including Bifidobac-terium and Lactobacillus
      promoted partial restoration of intestinal microflora and improved intestinal
      barrier function in malnourished rats after liver transplantation with long-term
      use of antibiotics.

PMID- 21947723
TI  - Collagen proportionate area of liver tissue determined by digital image analysis
      in patients with HBV-related decompensated cirrhosis.
AB  - BACKGROUND: The accurate assessment of the degree of hepatic fibrosis plays a
      critical role in guiding the diagnosis, treatment and prognostic assessment of
      chronic liver diseases. Liver biopsy is currently the most reliable method to
      evaluate the severity of hepatic fibrosis. However, liver biopsy is an invasive
      procedure associated with morbidity and mortality, and has several limitations in
      patients with decompensated cirrhosis. There is no report on the collagen
      proportionate area (CPA) of liver tissue in the decompensated stage of cirrhosis.
      This study aimed to determine the CPA of resected liver tissue samples from
      patients with HBV-related decompensated cirrhosis using digital image analysis,
      and to analyze the relationship between the CPA and liver functional reserve.
      METHODS: Fifty-three resected liver tissue samples from liver transplant patients
      with chronic hepatitis B-induced decompensated cirrhosis were stained with
      Masson's trichrome, and the CPA in these samples was quantitatively determined
      using digital image analysis. The values of relevant liver function just before
      liver transplantation, the CPA in liver tissue, and their correlation were
      analyzed. RESULTS: The mean CPA at the decompensated stage of cirrhosis was
      35.93+/-14.42% (11.24%-63.41%). The correlation coefficients of the CPA with a
      model for end-stage liver disease score, serum total bilirubin and international
      standard ratio of prothrombin B were 0.553, 0.519 and 0.533, respectively
      (P<0.001). With increasing CPA values, the three indices reflecting liver
      functional reserve also changed significantly. CONCLUSIONS: The degree of
      fibrosis may be correlated with the functional reserve. With the advancement of
      fibrosis, the liver functional reserve is attenuated accordingly.

PMID- 21947724
TI  - Salvianolic acid B modulates the expression of drug-metabolizing enzymes in HepG2
      cells.
AB  - BACKGROUND: Enzymes involved in drug and xenobiotic metabolism have been
      considered to exist in two groups: phase I and phase II enzymes. Cytochrome P450
      isoenzymes (CYPs) are the most important phase I enzymes in the metabolism of
      xenobiotics. The products of phase I metabolism are then acted upon by phase II
      enzymes, including glutathione S-transferases (GSTs). Herbs that inhibit CYPs
      such as CYP3A4 or that induce GSTs may have the potential to protect against
      chemical carcinogenesis since the mutagenic effects of carcinogens are often
      mediated through an excess of CYP-generated reactive intermediates. This study
      was designed to investigate the effects of salvianolic acid B (Sal B), a pure
      compound extracted from Radix Salviae Miltiorrhizae, a Chinese herb, on cell
      proliferation and CYP1A2 and CYP3A4 mRNA expression in the presence or absence of
      rifampicin, a potent inducer of CYPs and GST protein expression in HepG2 cells.
      METHODS: HepG2 cells were incubated with different concentrations of Sal B. Cell
      proliferation was determined by SYTOX-Green nucleic acid staining. CYP3A4 and
      CYP1A2 mRNA expression was assayed by real-time PCR. GST protein expression was
      analyzed by Western blotting. RESULTS: Low concentrations of Sal B (0-20 MUmol/L)
      had no significant effects on cell proliferation, while higher concentrations
      (100-250 MUmol/L) significantly inhibited proliferation in a concentration
      dependent manner. Ten MUmol/L Sal B, but not 1 MUmol/L, down-regulated CYP3A4 and
      CYP1A2 mRNA expression after 24 hours of incubation, whereas both 1 and 10
      MUmol/L Sal B down-regulated CYP3A4 mRNA expression after 96 hours of incubation;
      moreover, 1 and 10 MUmol/L Sal B inhibited CYP3A4 mRNA expression induced by
      rifampicin. Both 1 MUmol/L and 10 MUmol/L Sal B increased GST expression.
      CONCLUSION: Sal B inhibits CYP3A4 and CYP1A2 mRNA expression and induces GST
      expression in HepG2 cells.

PMID- 21947725
TI  - Preparation and characterization of chitosan porous microcarriers for hepatocyte
      culture.
AB  - BACKGROUND: The bioartificial liver (BAL) is considered a possible alternative
      method for treating liver failure. The core of the BAL system is culturing liver
      cells in vitro with high density and activity. Microcarrier culture is a mode of
      high-density culture. We set out to prepare a novel porous microcarrier to
      improve the activity of liver cells in vitro. METHODS: Chitosan was used to
      prepare a novel porous spherical microcarrier with interconnected structure. The
      chitosan porous microcarriers (CPMs) were modified with gelatin to improve their
      biocompatibility. CPMs were co-cultured with liver cells, HL-7702 (L-02), to
      evaluate their effect on cell culture. RESULTS: The average size of the CPMs was
      about 400 MUm in diameter and their apertures were less than 30 MUm. The pores of
      the microcarrier were interconnected. After fixation by sodium tripolyphosphate,
      the structure of the first freeze-dried CPMs was stable. To further improve the
      biocompatibility, the surface of CPMs was modified with gelatin through chemical
      crosslinking (GM-CPMs). Comparing the proliferation curves of L-02 cells cultured
      on simple CPMs, GM-CPMs and tissue culture polystyrene (TCPS, a mode of planar
      cell culture), the proliferation rates were similar in the first 5 days and the
      cells proliferated until day 8 in culture with microcarriers. The OD value of
      liver cells cultured on GM-CPMs was 1.97-fold higher than that on TCPS culture at
      day 8. Levels of urea and albumin in supernatants of cells cultured on GM-CPMs
      increased steadily for 8 days, and were clearly higher than those of cells
      cultured on TCPS (P<0.05). CONCLUSIONS: The novel CPMs were promising
      microcarriers for hepatocyte culture and the GM-CPM seemed better. Porous
      microcarrier culture was beneficial for hepatocyte function and activity.

PMID- 21947726
TI  - Hemodynamics and oxygen transport dynamics during hepatic resection at different
      central venous pressures in a pig model.
AB  - BACKGROUND: Although low central venous pressure (CVP) has been used to minimize
      blood loss during hepatectomy, the impact of variations of CVP on the rate of
      blood loss and on the perfusion of end-organs has not been evaluated. This animal
      study aimed to evaluate the hemodynamics and oxygen transport changes during
      hepatic resection at different CVP levels. METHODS: Forty-eight anesthetized Bama
      miniature pigs were divided into 8 groups with CVP during hepatic resection
      controlled at 0 to <1, 1 to <2, 2 to <3, 3 to <4, 4 to <5, 5 to <6, 6 to <7, and
      7 to <8 cmH2O. Intergroup comparisons were made for hemodynamic parameters,
      oxygen transport dynamics, and the rate of blood loss. RESULTS: The rate of blood
      loss and the hepatic venous pressure during hepatic resection were almost
      linearly related to the CVP. A significant drop in the mean arterial pressure,
      cardiac output, and cardiac index occurred between CVP >=2 and <2 cmH2O. Oxygen
      delivery (DO2), oxygen consumption (VO2) and oxygen extraction ratio (ERO2)
      remained relatively constant between CVPs of 2 to <8 cmH2O. There was a
      significant drop in DO2 when the CVP was <2 cmH2O. There was also a significant
      drop in VO2 and ExO2 when the CVP was <1 cmH2O. CONCLUSION: The optimal CVP for
      hepatic resection is 2 to 3 cmH2O.

PMID- 21947727
TI  - Single-port versus multi-port cholecystectomy for patients with acute
      cholecystitis: a retrospective comparative analysis.
AB  - BACKGROUND: Trans-umbilical single-port laparoscopic cholecystectomy for chronic
      gallbladder disease is becoming increasingly accepted worldwide. But so far, no
      reports exist about the challenging single-port surgery for acute cholecystitis.
      The objective of this study was to describe our experience with single-port
      cholecystectomy in comparison to the conventional laparoscopic technique.
      METHODS: Between August 2008 and March 2010, 73 patients with symptomatic
      gallbladder disease and histopathological signs of acute cholecystitis underwent
      laparoscopic cholecystectomy at our institution. Thirty-six patients were
      operated on with the single-port technique (SP group) and the data were compared
      with a control group of 37 patients who were treated with the multi-port
      technique (MP group). RESULTS: The mean age in the SP group was 61.5 (range 21
      81) years and in the MP group was 60 (range 21-94) (P=0.712). Gender, ASA status
      and BMI were not significantly different. The number of white blood cells was
      different before [SP: 9.2 (range 2.8-78.4); MP: 13.2 (range 4.4-28.6); P=0.001]
      and after the operation [SP: 7.8 (range 3.5-184.8); MP: 11.1 (range 5-20.8);
      P=0.002]. Mean operating time was 88 (range 34-174) minutes in the SP group vs 94
      (range 39-209) minutes in the MP group (P=0.147). Four patients (5%) required
      conversion to an open procedure (SP: 1; MP: 3; P=0.320). During the follow-up
      period of 332 (range 29-570) days in the SP group and 428 (range 111-619) days in
      the MP group (P=0.044), eleven (15%) patients developed postoperative
      complications (P=0.745) and two patients in the SP group required reoperation
      (P=0.154). CONCLUSIONS: Trans-umbilical single-port cholecystectomy for beginning
      acute cholecystitis is feasible and the complication rate is comparable with the
      standard multi-port operation. In spite of our good results, these operations are
      difficult to perform and should only be done in high-volume centers for
      laparoscopic surgery with experience in single-port surgery.

PMID- 21947728
TI  - Changing clinical profile, management strategies and outcome of patients with
      biliary tract injuries at a tertiary care center in Sri Lanka.
AB  - BACKGROUND: Biliary tract injuries are mostly iatrogenic. Related data are
      limited in developing countries. There are lessons to be learned by revisiting
      the clinical profiles, management issues and outcome of patients referred to a
      tertiary care center in Sri Lanka, compared with the previous data from the same
      center published in 2006. Such a review is particularly relevant at a time of
      changing global perceptions of iatrogenic biliary injuries. This study aimed to
      analyze and compare the changes in the injury pattern, management and outcome
      following biliary tract injury in a Sri Lankan study population treated at a
      tertiary care center. METHODS: A retrospective analysis was made of 67 patients
      treated between May 2002 and February 2011. The profiles of the last 38 patients
      treated from October 2006 to February 2011 were compared with those of the first
      29 patients treated from May 2002 to September 2006. Definitive management
      options included endoscopic biliary stenting, reconstructive hepaticojejunostomy
      with creation of gastric access loops, and biliary stricture dilation. Post
      treatment jaundice, cholangitis and abdominal pain needing intervention were
      considered as treatment failures. RESULTS: In the 67 patients, 55 were women and
      12 men. Their mean age was 40.6 (range 19-80) years. Five patients had traumatic
      injuries. Thirty-seven injuries (23 during the second study period) were due to
      laparoscopic cholecystectomy and 25 (10 during the second study period) to open
      cholecystectomy. The identification rate of intra-operative injury was 19% in the
      laparoscopic group and 8% in the open group. Bismuth type I, II, III and IV
      injuries were seen in 18, 18, 15 and 12 patients, respectively. Endoscopic
      stenting was the definitive treatment in 20 patients. In 35 patients who had
      hepaticojejunostomy, 33 underwent creation of the gastric access loop. Twenty-two
      reconstructions were performed during the second study period. A gastric access
      loop was used for endotherapy in three patients with anastomotic occlusion at the
      site of hepaticojejunostomy. The overall outcome was satisfactory in the majority
      of patients. There were four injury-related deaths. CONCLUSIONS: Biliary tract
      injuries associated with laparoscopic cholecystectomy have become the most
      frequent cause of biliary injury management at our center. Although endotherapy
      was useful in selected patients, in the majority, surgical reconstruction with
      hepaticojejunostomy was required as the definitive treatment. Creation of the
      gastric access loop was found to be a useful adjunct in the management of
      hepaticojejunostomy strictures.

PMID- 21947729
TI  - Effects of partial portal vein arterialization on the hilar bile duct in a rat
      model.
AB  - BACKGROUND: Liver revascularization is frequently required during the enlarged
      radical operation for hilar cholangiocarcinoma involving the hepatic artery.
      Researchers have carried out a number of experiments applying partial portal vein
      arterialization (PVA) in clinical practice. In this study we aimed to establish a
      theoretical basis for clinical application of partial PVA and to investigate the
      effects of partial PVA on rat hilar bile duct and hepatic functions. METHODS:
      Thirty rats were randomly and equally assigned into 3 groups: control (group A),
      hepatic artery ligation+bile duct recanalization (group B), and partial PVA+bile
      duct recanalization (group C). Proliferation and apoptosis of rat hilar bile duct
      epithelial cells, arteriolar counts of the peribiliary plexus (PBP) of the bile
      duct wall, changes in serum biochemistry, and pathologic changes in the bile duct
      were assessed 1 month after operation. RESULTS: The proliferation of hilar bile
      duct epithelial cells in group B was greater than in groups A and C (P<0.01). No
      apoptotic hilar bile duct epithelial cells were detected in any of the groups.
      The PBP arteriolar counts of the hilar bile duct wall were similar in groups A
      and C (P>0.05), but the count was lower in group B than in group A (P<0.01). No
      statistically significant differences in alanine aminotransferase, aspartate
      aminotransferase, alkaline phosphatase and albumin were found in the 3 groups.
      The gamma-glutamyltransferase value was higher in group B than in groups A and C
      (P<0.01). The hepatic tissues of groups A and C showed no significant
      abnormality. Chronic inflammatory changes in the hilar bile duct walls were
      observed only in group B. CONCLUSION: Partial PVA can restore the arterial blood
      supply of the hilar bile duct and significantly extenuate the injury to hilar
      bile duct epithelial cells resulting from hepatic artery ligation.

PMID- 21947730
TI  - Endoscopic pancreatic duct and biliary duct stenting in treatment of chronic
      pancreatitis with distal benign biliary stricture: a single-center experience.
AB  - BACKGROUND: The development of endoscopic techniques such as endoscopic
      retrograde cholangiopancreatography (ERCP), endoscopic sphincterotomy (EST) and
      stenting are relatively new alternatives to surgery for the treatment of benign
      lesions in the biliary duct and pancreas. The objective of this study was to
      assess the value of stenting in the endoscopic pancreatic duct and biliary duct
      in the treatment of chronic pancreatitis with distal benign biliary stricture.
      METHODS: Twenty-two patients diagnosed with chronic pancreatitis with distal
      benign biliary stricture underwent endoscopic treatment in our center, with ERCP,
      EST, endoscopic retrograde biliary drainage (ERBD) and endoscopic retrograde
      pancreatic drainage (ERPD) with stents. A numeric rating scale was used to assess
      pain intensity. The clinical data on endoscopic therapies and recovery of the
      patients were recorded and compared. RESULTS: ERCPs were successfully performed
      in 21 patients and 1 (4.5%) failed because of pancreatic ductal variation. A
      total of 68 ERCPs were performed with 47 pancreatic duct stents and 39 biliary
      duct stents. The rate of complications was 13.2% (9/68). The abdominal pain score
      after endoscopic treatment was significantly reduced. The levels of bilirubin and
      alanine transaminase in all 21 patients were improved compared to those before
      endoscopic treatment. CONCLUSION: Endoscopic stent drainage of the pancreatic
      duct and biliary duct for chronic pancreatitis with distal biliary benign
      stricture can be selected as a safe, effective and minimally invasive therapeutic
      method.

PMID- 21947732
TI  - Naproxen-induced liver injury.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to
      induce liver injury. Patterns of the injury usually range from mild elevations of
      liver enzymes to sometimes severe fulminant hepatic failure. Likewise, naproxen
      is a propionic acid derivative NSAID that was introduced in 1980 and has been
      available as an over-the-counter medication since 1994, but has rarely been
      reported to cause liver injury. METHODS: We treated a 30-year-old woman with
      jaundice and intractable pruritus that developed shortly after taking naproxen.
      We reviewed the medical history and liver histopathology of the patient as well
      as all previously published case reports of naproxen-associated liver toxicity in
      the English language literature. RESULTS: The liver biochemical profile of the
      patient revealed a mixed cholestasis and hepatitis pattern. Consecutive liver
      biopsies demonstrated focal lobular inflammation, hepatocyte drop-out, and a
      progressive loss of the small interlobular bile ducts (ductopenia). The biopsy
      performed two years after onset of the disease showed partial recovery of a small
      number of bile ducts; however, 10 years passed before the biochemical profile
      returned to near normal. CONCLUSIONS: Naproxen-associated liver toxicity remains
      a rare entity, but should be considered in any patient presenting with
      cholestasis shortly after its use. Liver injury is most commonly seen in a mixed
      pattern characterized by cholestasis and hepatitis. The resulting liver damage
      may take years to resolve.

PMID- 21947731
TI  - Protective effect of clodronate-containing liposomes on intestinal mucosal injury
      in rats with severe acute pancreatitis.
AB  - BACKGROUND: Severe acute pancreatitis (SAP) can result in intestinal mucosal
      injury. This study aimed to demonstrate the protective effect of clodronate
      containing liposomes on intestinal mucosal injury in rats with SAP. METHODS:
      Liposomes containing clodronate or phosphate buffered saline (PBS) were prepared
      by the thin-film method. SAP models were prepared by a uniform injection of
      sodium taurocholate (2 mL/kg body weight) into the subcapsular space of the
      pancreas. Sprague-Dawley rats were randomly divided into a control group (C
      group), a SAP plus PBS-containing liposomes group (P group) and a SAP plus
      clodronate-containing liposomes group (T group). At 2 and 6 hours after the
      establishment of SAP models, 2 mL blood samples were taken from the superior
      mesenteric vein to measure the contents of serum TNF-alpha and IL-12.
      Pathological changes in the intestine and pancreas were observed using
      hematoxylin and eosin staining, while apoptosis was detected using TUNEL
      staining. In addition, the macrophage markers cluster of differentiation 68
      (CD68) in the intestinal tissue was assessed with immunohistochemistry. RESULTS:
      At the two time points, the levels of TNF-alpha and IL-12 in the P group were
      higher than those in the C group (P<0.05). Compared with the P group, the levels
      of TNF-alpha and IL-12 decreased in the T group (P<0.05). The pathological scores
      of the intestinal mucosa and pancreas in the T group were lower than those of the
      P group. In the T group, large numbers of TUNEL-positive cells were observed, but
      none or few in the C and P groups. The number of CD68-positive macrophages
      decreased in the T group. CONCLUSIONS: Clodronate-containing liposomes have
      protective effects against intestinal mucosal injury in rats with SAP. The
      blockade of macrophages may provide a novel therapeutic strategy in SAP.

PMID- 21947733
TI  - Hepatitis E virus-related acute liver failure associated with pure red cell
      aplasia.

PMID- 21947734
TI  - Bone mineral density and body composition of South African cricketers.
AB  - Mechanical loading associated with weight-bearing physical activity has been
      positively associated with bone mineral density in athletes participating in
      various sports. The aim of this study was to compare the body composition and
      bone mineral density of South African male cricketers to controls. Whole body
      (WB), femoral neck (FN), proximal femur (PF) and lumbar spine (LS) BMD, as well
      as whole body fat mass (WBFM) and lean mass (WBLM) were measured, using dual
      energy X-ray absorptiometry (DXA), on 34 high-performance (senior provincial and
      national level) cricketers and 23 physically active controls between the ages of
      16 and 34 years. Cricketers were significantly younger, taller, and had greater
      WBLM and WBBMC compared to the controls. LS, PF and FN BMD were higher in the
      cricketers and controls before and after adjusting for age and height. WBBMD was
      significantly lower in the spin bowlers compared to the batsmen and fast bowlers,
      after adjusting for age and height; however, there were no differences at the BMD
      sites between the groups. Bone mineral density at the lumbar spine and hip sites
      was significantly greater in the cricketers compared to the controls, suggesting
      that the mechanical loading associated with cricket is beneficial for bone
      mineral density.

PMID- 21947735
TI  - Hypervolemic hypernatremia in patients recovering from acute kidney injury in the
      intensive care unit.
AB  - BACKGROUND: A high incidence of hypernatremia is often observed in patients
      recovering from acute kidney injury (AKI) in intensive care units. METHODS: An
      unselected cohort of 20 adult patients recovering from AKI in the intensive care
      unit of a single institution during a 1-year period, were investigated. Serum and
      urine electrolytes, osmolality, urea nitrogen and creatinine were measured in an
      attempt to determine the cause of the hypernatremia. RESULTS: Eighty-eight
      percent of patients who could not drink fluids were found to have hypernatremia
      (serum Na >145 mEq/L). Even though the hypernatremia was mild in most patients
      (146-160 mEq/L), the average rise in serum sodium concentration was 17.4 mEq/L.
      The average urine osmolality was 384 mmol/kg of which 47.6 and 32.8 mmol/kg were
      contributed by sodium and potassium, respectively. The patients had hypervolemia
      as evidenced by the presence of edema and an average weight gain of 21.5 kg at
      the onset of the hypernatremia. The rise in serum sodium level coincided with an
      increase in urine output. CONCLUSION: The hypernatremia is believed to be due to
      post-AKI diuresis in the face of inability to maximally concentrate the urine
      because of renal failure. The diuresis caused a disproportionate loss of water in
      excess of that of sodium in the absence of replenishment of the water loss.
      Additionally, the patients were hypervolemic due to the retention of large
      quantities of sodium and water as a result of infusion of substantial volumes of
      physiological saline prior to the development of hypernatremia.

PMID- 21947736
TI  - Development, validation, and application of a parametric pediatric head finite
      element model for impact simulations.
AB  - In this study, a statistical model of cranium geometry for 0- to 3-month-old
      children was developed by analyzing 11 CT scans using a combination of principal
      component analysis and multivariate regression analysis. Radial basis function
      was used to morph the geometry of a baseline child head finite element (FE) model
      into models with geometries representing a newborn, a 1.5-month-old, and a 3
      month-old infant head. These three FE models were used in a parametric study of
      near-vertex impact conditions to quantify the sensitivity of different material
      parameters. Finally, model validation was conducted against peak head
      accelerations in cadaver tests under different impact conditions, and
      optimization techniques were used to determine the material properties. The
      results showed that the statistical model of cranium geometry produced realistic
      cranium size and shape, suture size, and skull/suture thickness, for 0- to 3
      month-old children. The three pediatric head models generated by morphing had
      mesh quality comparable to the baseline model. The elastic modulus of skull had a
      greater effect on most head impact response measurements than other parameters.
      Head geometry was a significant factor affecting the maximal principal stress of
      the skull (p = 0.002) and maximal principal strain of the suture (p = 0.021)
      after controlling for the skull material. Compared with the newborn head, the 3
      month-old head model produced 6.5% higher peak head acceleration, 64.8% higher
      maximal principal stress, and 66.3% higher strain in the suture. However, in the
      skull, the 3-month-old model produced 25.7% lower maximal principal stress and
      11.5% lower strain than the newborn head. Material properties of the brain had
      little effects on head acceleration and strain/stress within the skull and
      suture. Elastic moduli of the skull, suture, dura, and scalp determined using
      optimization techniques were within reported literature ranges and produced
      impact response that closely matched those measured in previous cadaver tests.
      The method developed in this study made it possible to investigate the age
      effects from geometry changes on pediatric head impact responses. The parametric
      study demonstrated that it is important to consider the material properties and
      geometric variations together when estimating pediatric head responses and
      predicting head injury risks.

PMID- 21947737
TI  - The family-school-primary care triangle and the access to mental health care
      among migrant and ethnic minorities.
AB  - Understanding the concepts of mental health and help seeking behaviours of
      migrant and ethnic minority families constitutes an important step toward
      improving the intercultural competence of health and education professionals.
      This paper addresses these goals among ethnic and migrant minorities in Portugal.
      For this a multi-informant approach was selected. The study involved nine focus
      groups (N = 39) conducted with different samples: young immigrants (12-17 years),
      immigrant parents, teachers and health professionals. The results showed
      similarities and differences in concepts of mental health, as well as help
      seeking processes. Stigma continued to be recognized as a barrier in the access
      to mental health care. The paper argues that providing adequate training on
      mental health on cultural diversity competencies to health and education
      professionals can contribute to a better inter-communication and -relation system
      in the family-school-primary care triangle and thus facilitate access to mental
      health care for youth.

PMID- 21947738
TI  - Where would you rather live if you were insured? Assessing community uninsurance
      spillover effects on the insured.
AB  - This study sought to understand the cost, quality of, and access to health care
      for the insured population in the context of spillover effects resulting from
      community-level uninsurance. We examined the health care access, quality, and
      cost experienced by insured Latina mothers in two communities, Minneapolis,
      Minnesota and McAllen, Texas. These communities differ substantially by the size
      of the local population without health insurance coverage. Four focus groups were
      conducted with insured Latina mothers who were caring for at least one child in
      their household. Eleven and thirteen mothers participated in each community,
      respectively. The experiences of the insured population in McAllen were
      substantially different from the experiences of the insured population in
      Minneapolis. The perceptions of health care quality and access by insured Latina
      mothers were substantially lower in McAllen while out-of-pocket costs were
      perceived to be higher in Minneapolis. Our study provides key insights about the
      US health care system and the role that the relative size of the local uninsured
      population may have in impacting the health care experiences of the insured.
      Health insurance coverage rates are expected to increase substantially across US
      communities within the next few years but local health care system challenges
      related to cost, quality, and access will remain for both the insured and the
      uninsured.

PMID- 21947739
TI  - Verification of surface contamination of Japanese cyclophosphamide vials and an
      example of exposure by handling.
AB  - PURPOSE: Cyclophosphamide (CP) contamination has been detected in Japanese
      hospitals. In other countries, the surface contamination of CP vials has been
      reported; however, the manufacturing process of Japanese CP vials is unknown, so
      the conditions are not necessarily the same as in other countries. This study
      aimed to establish whether vial surface contamination also occurs in Japan.
      METHOD: Contamination of vial surfaces was examined with a wipe test. Urine
      samples were taken from a pharmacist, engaged solely in dispensing work, for 29
      h. It was also investigated whether CP vials were dispensed during the urine
      sampling period. In addition, vial surfaces, purposely coated with CP and then
      washed, were examined using wipe tests. RESULT: CP was detected at 30-60% in
      vials, which was 11-62 ng (0.10-0.54 ng/cm(2)). One of the urine samples was
      contaminated (CP 13.5 ng); this was taken on Day 2 (11:35 AM). CP was not
      detected among the washed vials. DISCUSSION: This study shows that the surface of
      Japanese CP vials was contaminated and that it was probable that healthcare
      workers were exposed to CP. CP absorption by the pharmacist was probably due to
      dermal uptake while dispensing. Washing the vial is considered effective to avoid
      CP exposure. Manufacturers should be more proactive to prevent contamination and
      healthcare workers should comply with exposure prevention rules. Cytotoxic drugs
      should be included in institution monitoring lists.

PMID- 21947741
TI  - Totally transvaginal resection of the descending colon in an experimental model.
AB  - BACKGROUND: Natural orifice translumenal endoscopic surgery (NOTES), although in
      its embryonic phase, is currently experiencing important developments. The
      technique has been successfully applied for cholecystectomies and appendectomies.
      However, several doubts exist as to the technical limitations and feasibility of
      NOTES in other clinical settings. METHODS: The authors have performed totally
      transvaginal colon resections in a sheep model. Although completion of the
      surgery was possible through the transvaginal route, the addition of a
      transumbilical laparoscope was used as an added safety measure. RESULTS: Totally
      transvaginal resection of the sigmoid colon was performed for two sheep with no
      intra- or postoperative complications. CONCLUSION: Totally transvaginal resection
      of the colon (pure NOTES) is feasible in a sheep model.

PMID- 21947742
TI  - Value of multidetector computed tomography image segmentation for preoperative
      planning in general surgery.
AB  - BACKGROUND: Using practical examples, this report aims to highlight the clinical
      value of patient-specific three-dimensional (3D) models, obtained segmenting
      multidetector computed tomography (MDCT) images, for preoperative planning in
      general surgery. METHODS: In this study, segmentation and 3D model generation
      were performed using a semiautomatic tool developed in the authors' laboratory.
      Their segmentation procedure is based on the neighborhood connected region
      growing algorithm that, appropriately parameterized for the anatomy of interest
      and combined with the optimal segmentation sequence, generates good-quality 3D
      images coupled with facility of use. Using a touch screen monitor, manual
      refining can be added to segment structures unsuitable for automatic
      reconstruction. Three-dimensional models of 10 candidates for major general
      surgery procedures were presented to the operating surgeons for evaluation. A
      questionnaire then was administered after surgery to assess the perceived added
      value of the new technology. RESULTS: The questionnaire results were very
      positive. The authors recorded the diffuse opinion that planning the procedure
      using a segmented data set allows the surgeon to plan critical interventions with
      better awareness of the specific patient anatomy and consequently facilitates
      choosing the best surgical approach. CONCLUSIONS: The benefit shown in this
      report supports a wider use of segmentation software in clinical practice, even
      taking into account the extra time and effort required to learn and use these
      systems.

PMID- 21947744
TI  - Sensing the main health concerns in patients with established rheumatoid
      arthritis.
AB  - The principle objective was to determine the spectrum of some health concerns
      that are likely to be present in patients with established rheumatoid arthritis
      (RA) in patients living in United Arab Emirates. One hundred and one RA patients
      and 82 with other arthropathies, predominantly Arab individuals, were interviewed
      for main health concerns while receiving antirheumatic drug therapy. All were
      requested to indicate and prioritize their first three concerns. Setting up the
      list of concerns was based on previous conclusions to the question of "What
      bothers you most with your disease?" Pain attributed to the disease was the
      predominant concern in both groups: 82% vs. 71%, p=NS. Pain was also prioritized
      by the RA patients in the first rank, n=52/82 patients, and surpassed its
      prioritization in the second and third ranks combined (63.5% vs. 36.5%, p=0.001).
      Fear of future disability came second in RA patients, 50% vs. 25.5% in the other
      group, p=0.001. Depressive feeling surprisingly was more dominant in patients
      with other arthropathies, 35.5% vs. 20% in RA patients, p=0.001. In the
      prioritization of concerns, the fear of disability was first ranked by 24% of RA
      patients compared to 8.5% by patients with other arthropathies (p=0.009) while
      the latter patients were significantly concerned about depressive feeling and
      fatigue compared to RA patients (7% vs. 0%, p=0.007 and 14.5% vs. 5%, p=0.04,
      respectively). Significant hand deformities was noticed in 25 RA patients (25%);
      however, only 11 of those (44.5%) indicated their fear of disability compared to
      the others who did not (p = NS, OR = 0.73, and 95% CI 0.275-1.665). Therefore in
      this predominantly Arab cohort, pain is the main health concern for RA patients
      and patients with other arthropathies. Patients with RA are more concerned about
      becoming disabled, while other patients are more concerned with feeling depressed
      or fatigued. Those lived with phobia of disability in RA patients did that
      irrespective to the presence or absence of significant hand deformities.

PMID- 21947740
TI  - IL-23 in infections, inflammation, autoimmunity and cancer: possible role in HIV
      1 and AIDS.
AB  - The growing family of interleukin (IL)-12-like cytokines produced by activated
      macrophages and dendritic cells became the important players in the control of
      infections, development of inflammation, autoimmunity and cancer. However, the
      role of one of them-heterodimer IL-23, which consists of IL12p40 and the unique
      p19 subunit in HIV-1 infection pathogenesis and progression to AIDS, represent
      special interest. We overviewed findings of IL-23 involvement in control of
      peripheral bacterial pathogens and opportunistic infection, central nervous
      system (CNS) viral infections and autoimmune disorders, and tumorogenesis, which
      potentially could be applicable to HIV-1 and AIDS.

PMID- 21947745
TI  - Setting sights higher: category-level attentional set modulates sustained
      inattentional blindness.
AB  - Previous research has shown that inattentional blindness is modulated by how
      people tune their "attentional set": the more featurally similar the unexpected
      object is to what people are trying to attend, the more likely it is that they
      will notice it. The experiments in this paper show that people can also establish
      attentional sets based on semantic categories, and that these high-level
      attentional sets modulate sustained inattentional blindness. In "Experiment 1",
      participants tracked four moving numbers and ignored four moving letters or vice
      versa, and the unexpected object was either a capital letter 'E' or its reverse,
      a block-like number '3'. Despite their featural similarity, participants were
      more likely to notice the unexpected object belonging to the same category as the
      tracked objects. "Experiment 2" replicated this effect in conditions where the
      unexpected object possessed a unique luminance and was less likely simply to be
      confused with other display items.

PMID- 21947746
TI  - Investigation on the improvement and transfer of dual-task coordination skills.
AB  - Recent research has demonstrated that dual-task performance in situations with
      two simultaneously presented tasks can be substantially improved with extensive
      practice. This improvement was related to the acquisition of task coordination
      skills. Earlier studies provided evidence that these skills result from hybrid
      practice, including dual and single tasks, but not from single-task practice. It
      is an open question, however, whether task coordination skills are independent
      from the specific practice situation and are transferable to new situations or
      whether they are non-transferable and task-specific. The present study,
      therefore, tested skill transfer in (1) a dual-task situation with identical
      tasks in practice and transfer, (2) a dual-task situation with two tasks changed
      from practice to transfer, and (3) a task switching situation with two
      sequentially presented tasks. Our findings are largely consistent with the
      assumption that task coordination skills are non-transferable and task-specific.
      We cannot, however, definitively reject the assumption of transferable skills
      when measuring error rates in the dual-task situation with two changed tasks
      after practice. In the task switching situation, single-task and hybrid practice
      both led to a transfer effect on mixing costs.

PMID- 21947747
TI  - GEMOX regimen in the treatment of metastatic differentiated refractory thyroid
      carcinoma.
AB  - Treatment options for radioiodine resistant metastatic thyroid cancer patients
      are limited, and chemotherapy is considered an outdated therapeutic method for
      differentiated thyroid carcinoma. In this study, we evaluated the activity and
      safety of gemcitabine and oxaliplatin combination which is considered an out of
      label therapeutic method in patients with differentiated metastatic thyroid
      cancer refractory to 131-I treatment. Fourteen refractory patients (8 papillary,
      6 follicular), six men/eight women with median age of 63 years and performance
      status (0-3) were included. Patients received gemcitabine (1,000 mg/m(2)) plus
      oxaliplatin (100 mg/m(2)) every 2 weeks until 12-cycles and each cycle correspond
      to 2 weeks treatment. This protocol was approved by the local Institutional
      Review Boards. Response rate was assessed every four cycles. Progression-free and
      overall survivals were calculated. Median treatment was 9.5 cycles (range 2-17)
      with 22 weeks duration. Overall response rate was 57%, with 7% achieving a
      complete response (1/14), 50% a partial response (7/14), and 28% with a stable
      disease. All patients with follicular subtype showed objective responses. Eleven
      patients progressed at a median time of 10.1 months; 10 of 14 patients still
      alive and the median survival was not reached (median follow-up of 19.8 months).
      The combination was generally well tolerated. No deaths occurred due to therapy
      and no grade IV toxicity was recorded. The most common treatment-related adverse
      events grade 1/3 includes asthenia, peripheral neuropathy, diarrhea, anemia,
      thrombocytopenia, and neutropenia. In conclusion, the GEMOX regimen is well
      tolerated and effective in advanced differentiated thyroid cancer. However, this
      retrospective data on a small sample size are considered preliminary and needs to
      be evaluated prospectively in a higher number of patients in a clinical trial.

PMID- 21947748
TI  - Expression of Plakophilins (PKP1, PKP2, and PKP3) in breast cancers.
AB  - Plakophilins (PKP) are desmosomal plague proteins, which belong to the p120ctn
      subfamily of armadillo repeat containing proteins. We aimed to analyze the role
      of plakophilins in breast cancer and its clinical progress. We have performed
      immunohistochemical study of the PKP1,2,3 in breast carcinoma. The study included
      108 patients with breast cancer and 26 age- and sex-matched healthy controls. We
      investigated the associations between staining intensity and some
      clinicopathologic features like tumor size, axillary node status, stage,
      lymphovascular invasion, perineural invasion, grade, hormone receptor status, and
      c-erb B2. The mean age of patients was 46 years (22-78). In breast cancer,
      compared with normal tissue, PKP1 and PKP2 expressions were indifferent (P >
      0.05), but PKP3 expression was significantly increased in breast cancer (P =
      0.0014). Although PKP1 and PKP2 expression levels were not correlated with
      clinicopathological parameters, increased PKP3 expression was positively
      correlated with node positivity and grade (P = 0.000, P = 0.000). CONCLUSION:
      Overexpressed PKP3 is likely to be an essential contributor to a growth-promoting
      pathway and to aggressive features of breast cancer.

PMID- 21947749
TI  - Comparison of preclinical cardiotoxic effects of different ErbB2 inhibitors.
AB  - Two novel human antitumor immunoconjugates, made up of a human anti-ErbB2 scFv,
      Erbicin, fused with either a human RNase or the Fc region of a human IgG1, are
      selectively cytotoxic for ErbB2-positive cancer cells in vitro and in vivo. The
      Erbicin-derived immunoagents (EDIA) target an epitope different from that of
      trastuzumab, the only humanized antibody currently prescribed for treatment of
      ErbB2-positive breast cancer (BC). As Trastuzumab has shown cardiotoxic effects,
      in this study, we evaluated if any side effects were exerted also by EDIA, used
      as single agents or in combination with anthracyclines. Furthermore, we compared
      the in vitro and in vivo cardiotoxic effects of EDIA with those of the other
      available anti-ErbB2 drugs: Trastuzumab, 2C4 (Pertuzumab), and Lapatinib. In this
      article, we show that EDIA, in contrast with Trastuzumab, 2C4, and Lapatinib,
      have no toxic effects on human fetal cardiomyocytes in vitro, and do not induce
      additive toxicity when combined with doxorubicin. Furthermore, EDIA do not impair
      cardiac function in vivo in mice, as evaluated by Color Doppler echocardiography,
      whereas Trastuzumab significantly reduces radial strain (RS) at day 2 and
      fractional shortening (FS) at day 7 of treatment in a fashion similar to
      doxorubicin. Also 2C4 and Lapatinib significantly reduce RS after only 2 days of
      treatment, even though they showed cardiotoxic effects less pronounced than those
      of Trastuzumab. These results strongly indicate that RS could become a reliable
      marker to detect early cardiac dysfunction and that EDIA could fulfill the
      therapeutic need of patients ineligible to Trastuzumab treatment because of
      cardiac dysfunction.

PMID- 21947750
TI  - Vascular proliferation is a prognostic factor in breast cancer.
AB  - Angiogenesis is important for the growth and spread of malignant tumors, and anti
      angiogenesis treatment is currently being evaluated for breast cancer and other
      tumors. Although microvessel density is the most commonly used tissue-based
      marker of tumor associated angiogenesis, it has significant limitations and has
      not proven effective as a predictive factor in selecting patients for treatment.
      We here wanted to explore the significance of vascular endothelial cell
      proliferation in breast carcinoma. We examined microvessel proliferation in
      breast cancer by dual immunohistochemical staining, using the pan-endothelial
      marker Factor-VIII combined with proliferation of endothelial cells by Ki-67
      expression, in three independent series of breast cancer, including a total of
      499 patients and 141 events during follow-up. Common statistical tests of
      associations as well as univariate and multivariate regression analysis of
      patient survival were used. By counting vessels with actively proliferating
      endothelium, we show that microvascular proliferation is a significant predictor
      of disease progression in breast cancer, especially among high-grade and ER
      negative tumors. Our findings indicate that this novel marker of active tumor
      angiogenesis might be of value in patient management and should be further
      studied in the context of patient selection for anti-angiogenesis treatment.

PMID- 21947751
TI  - Bloody nipple discharge is a predictor of breast cancer risk: a meta-analysis.
AB  - Nipple discharge is a common complaint of patients with breast disease. The color
      of nipple discharge is always the first alarming symptom for patients. It is
      controversial whether the discharge color is an indicator of an underlying
      malignancy. The electronic database PubMed was searched for relevant articles. A
      meta-analysis about the association between the color of nipple discharge and
      breast cancer risk was conducted. Eight studies, including 3,110 patients, were
      eligible for this meta-analysis. Compared with patients in non-bloody nipple
      discharge group (179/1,478), patients in bloody nipple discharge group
      (404/1,632) had a markedly higher breast cancer risk (OR: 2.27, 95% CI: 1.32
      3.89, P < 0.001 for heterogeneity). Compared with patients in clear/serous group
      (71/575), patients in bloody nipple discharge group (326/1,271) also had a higher
      risk (OR: 2.49, 95% CI: 1.25-4.93, P = 0.011 for heterogeneity). Furthermore,
      compared with patients in the colored group (55/448), patients in bloody nipple
      discharge group (296/1,124) (OR: 2.00, 95% CI: 0.74-5.45, P = 0.009 for
      heterogeneity) had no significant difference. Besides, there was no significant
      difference between patients in colored group (55/448) and clear/serous group
      (61/470) (OR: 1.35, 95% CI: 0.83-2.18, P = 0.707 for heterogeneity). Therefore,
      bloody nipple discharge could be a predictor of breast cancer risk among
      different colors of discharges. The symptom of bloody nipple discharge is helpful
      to the stratification of preoperative patients.

PMID- 21947752
TI  - The BRCA2 c.9004G>A (E2002K) [corrected] variant is likely pathogenic and recurs
      in breast and/or ovarian cancer families of French Canadian descent.
AB  - Specific BRCA1 and BRCA2 mutations recur in French Canadian breast and/or ovarian
      cancer families because of common ancestors, facilitating carrier detection in
      this population. We recently reported a BRCA2 c.9004G>A variant of unknown
      clinical significance in two French Canadian breast cancer families. It confers a
      E3002K alteration in the conserved C-terminus domain of BRCA2, and has been
      reported in non-French Canadian cancer families. Seven variant positive French
      Canadian families have since been identified by mutation screening of referrals
      to hereditary cancer clinics. In this article, we describe the cancer phenotypes
      of these families and further assess the contribution of this variant in the
      French Canadian population. We screened index breast cancer cases from 58 cancer
      families with at least three confirmed cases of breast and/or ovarian cancer and
      960 breast cancer cases (48 years mean age) not selected for family history of
      cancer that were previously found not to carry the most common BRCA1 and BRCA2
      mutations reported in this population. The index variant-positive cases from each
      family had breast cancer between the ages of 35-55 years (43 years mean age); and
      reported close relatives with breast cancer diagnoses between the ages of 28-84
      years (57 years mean age). Three families had ovarian or peritoneal cancers.
      BRCA2-associated cancers, such as bladder, esophagus, pancreas, prostate, and
      thyroid cancers also occurred in these families. One c.9004G>A carrier also
      harbored the PALB2 c.2323C>T (Q775X) mutation found to recur in French Canadian
      breast cancer cases. No new BRCA2 variant carriers were identified in mutation
      screens. The absence of BRCA2 c.9004G>A carriers in the breast cancer cases not
      selected for family history contrasts with familial cases, supporting a
      pathogenic status for this variant and addition to the existing common BRCA1 and
      BRCA2 mutation-screening panel for French Canadian breast and/or ovarian cancer
      families.

PMID- 21947753
TI  - Effect of tranexamic acid on blood loss in pediatric cardiac surgery: a
      randomized trial.
AB  - PURPOSE: The benefit of tranexamic acid (TXA) in pediatric cardiac surgery on
      postoperative bleeding has varied among studies. It is also unclear whether the
      effects of TXA differ between cyanotic patients and acyanotic patients. The aim
      of this study was to test the benefit of TXA in pediatric cardiac surgery in a
      well-balanced study population of cyanotic and acyanotic patients. METHODS: A
      total of 160 pediatric patients undergoing cardiac surgery with cardiopulmonary
      bypass (81 cyanotic, 79 acyanotic) were included in this single-blinded,
      randomized trial at a tertiary care university-affiliated teaching hospital.
      Eighty-one children (41 cyanotic, 40 acyanotic) were randomly assigned to a TXA
      group, in which they received 50 mg/kg of TXA as a bolus followed by 15 mg/kg/h
      infusion and another 50 mg/kg into the bypass circuit. The other 79 patients were
      randomly assigned to a placebo group. The primary end point was the amount of 24
      h blood loss. RESULTS: The amount of 24-h blood loss was significantly less in
      the TXA group than in the placebo group [mean (95% confidence interval): 18.6
      (15.8-21.4) vs. 23.5 (19.4-27.5) ml/kg, respectively; mean difference -4.9 (-9.7
      to -0.01) ml/kg; p = 0.049]. This effect of TXA was already significant at 6 h
      [9.5 (7.5-11.5) vs. 13.2 (10.6-15.9) ml/kg, respectively; mean difference -3.47 (
      7.0 to -0.4) ml/kg; p = 0.027]. However, there was no significant difference in
      the amount of blood transfusion between the groups. There was also no statistical
      difference in the effect of TXA in each cyanotic and acyanotic subgroup.
      CONCLUSION: TXA can reduce blood loss in pediatric cardiac surgery but not the
      transfusion requirement (http://ClinicalTrials.gov number NCT00994994).

PMID- 21947754
TI  - Comparison of recovery times from rocuronium-induced muscle relaxation after
      reversal with three different doses of sugammadex and succinylcholine during
      electroconvulsive therapy.
AB  - PURPOSE: This study was conducted to compare recovery times from rocuronium
      induced muscle relaxation after reversal with three different doses of sugammadex
      with succinylcholine during electroconvulsive therapy (ECT). METHODS: Seventeen
      patients who were scheduled to undergo ECT were studied. Anesthesia was induced
      by use of propofol (1.0 mg/kg) followed by either succinylcholine (SCC) (1 mg/kg)
      or rocuronium (0.6 mg/kg). Assisted mask ventilation was initiated with 100%
      oxygen. After T1 was assessed as being zero by neuromuscular monitoring, an
      electroshock stimulus was applied bilaterally. Patients receiving rocuronium were
      infused with 16, 8, or 4 mg/kg sugammadex immediately after the seizure stopped
      to reverse the muscle relaxation. Neuromuscular monitoring was continued until
      recovery of the train-of-four ratio to 0.9 at the tibial nerve in the leg. The
      times to recovery of T1 to 10 and 90% with both relaxants were compared. RESULTS:
      The time to recovery of T1 to 90% after 16 mg/kg sugammadex was shorter than that
      in subjects treated with SCC (p = 0.046), whereas that after 4 mg/kg sugammadex
      was longer than that in subjects treated with SCC (SCC group: 429 +/- 65 s, 16
      mg/kg sugammadex group: 387 +/- 63 s*, 8 mg/kg sugammadex group: 462 +/- 66 s, 4
      mg/kg sugammadex group: 563 +/- 45 s(*,#); *p < 0.05 compared with SCC, (#)p <
      0.01 compared with 16 mg/kg sugammadex). CONCLUSIONS: This study demonstrates the
      efficacy of rocuronium-sugammadex as an alternative to SCC for muscle relaxation
      during ECT, and indicates that 8 mg/kg sugammadex produces equally rapid recovery
      from rocuronium muscular relaxation compared with spontaneous recovery from 1
      mg/kg SCC during ECT.

PMID- 21947755
TI  - Molecular breeding of transgenic white clover (Trifolium repens L.) with field
      resistance to Alfalfa mosaic virus through the expression of its coat protein
      gene.
AB  - Viral diseases, such as Alfalfa mosaic virus (AMV), cause significant reductions
      in the productivity and vegetative persistence of white clover plants in the
      field. Transgenic white clover plants ectopically expressing the viral coat
      protein gene encoded by the sub-genomic RNA4 of AMV were generated. Lines
      carrying a single copy of the transgene were analysed at the molecular,
      biochemical and phenotypic level under glasshouse and field conditions. Field
      resistance to AMV infection, as well as mitotic and meiotic stability of the
      transgene, were confirmed by phenotypic evaluation of the transgenic plants at
      two sites within Australia. The T(0) and T(1) generations of transgenic plants
      showed immunity to infection by AMV under glasshouse and field conditions, while
      the T(4) generation in an agronomically elite 'Grasslands Sustain' genetic
      background, showed a very high level of resistance to AMV in the field. An
      extensive biochemical study of the T(4) generation of transgenic plants, aiming
      to evaluate the level and composition of natural toxicants and key nutritional
      parameters, showed that the composition of the transgenic plants was within the
      range of variation seen in non-transgenic populations.

PMID- 21947757
TI  - Reducing inter-observer variability in embryo evaluation by means of training
      courses.
AB  - PURPOSE: To study the utility of a training session offered to junior
      embryologists, comparing the results obtained with those reported by a group of
      senior embryologists. METHODS: The 62 junior embryologists participanting were
      asked to decide on the quality of the embryos and theg clinical decision to be
      taken. RESULTS: The junior embryologists' success rate following the training
      course was significantly higher than before for embryo classification (48.4% +/-
      20.4 vs. 59.7% +/-16.7) (p < 0.05) and for clinical decision (54.7% +/- 19.6 vs.
      68.7% +/- 17.6) (p < 0.005). Comparison of the degree of agreement between the
      categories assigned by the junior embryologists and those assigned by consensus
      among the group of senior embryologists revealed kappa values of k = 0.32 before
      the course and of k = 0.54 after it. The comparison between pre- and post
      training junior and senior embryologists also reflected an improvement in the
      kappa index for clinical decision, from k = 0.54 to k = 0.68. CONCLUSIONS:
      Training courses are shown to be an effective tool for increasing the degree of
      agreement between junior and senior embryologists.

PMID- 21947758
TI  - In vitro fertilization and embryo transfer outcomes in relation to myometrial
      thickness.
AB  - PURPOSE: To evaluate the effects of myometrial thickening on the outcomes of in
      vitro fertilization and embryo transfer (IVF-ET). METHODS: Four hundred thirteen
      patients, a total of 551 IVF-ET cycles, were divided into group A (<2.00 cm),
      group B (2.00-2.49 cm), and group C (>=2.50 cm) based on myometrial thickness.
      RESULTS: The implantation, clinical pregnancy, and live birth rates were
      significantly lower in group C. The abortion rates were significantly higher in
      group C. Among patients in group B, cases with other sonographic findings
      suggestive of adenomyosis, such as myometrial striations, heterogeneous
      myometrium, myometrial cysts, and poor definition of the endometrial-myometrial
      junction showed lower implantation, clinical pregnancy, live birth rates, and
      higher abortion rates. CONCLUSIONS: Myometrial thickening of more than 2.50 cm on
      TVUS exerts overall adverse effects on IVF-ET outcomes. Even with mild thickening
      (2.00-2.49 cm), the presence of sonographic findings suggestive of adenomyosis is
      associated with adverse outcomes of IVF-ET.

PMID- 21947759
TI  - Combining 2D and 3D in silico methods for rapid selection of potential PDE5
      inhibitors from multimillion compounds' repositories: biological evaluation.
AB  - Rapid in silico selection of target focused libraries from commercial
      repositories is an attractive and cost-effective approach when starting new drug
      discovery projects. If structures of active compounds are available rapid 2D
      similarity search can be performed on multimillion compounds' databases. This in
      silico approach can be combined with physico-chemical parameter filtering based
      on the property space of the active compounds and 3D virtual screening if the
      structure of the target protein is available. A multi-step virtual screening
      procedure was developed and applied to select potential phosphodiesterase 5
      (PDE5) inhibitors in real time. The combined 2D/3D in silico method resulted in
      the identification of 14 novel PDE5 inhibitors with <1 MUMIC(50) values and the
      hit rate in the second in silico selection and in vitro screening round exceeded
      the 20%.

PMID- 21947760
TI  - Purification, characterization, and molecular cloning of a novel antifungal
      lectin from the roots of Ophioglossum pedunculosum.
AB  - A novel mannan-specific lectin was isolated from the roots of a traditional
      Chinese herbal medicine, Ophioglossum pedunculosum through ion-exchange
      chromatography and gel filtration. With a molecular mass of 19,835.7 Da
      demonstrated by MALDI-TOF analysis, this novel agglutinin was designated as O.
      pedunculosum agglutinin (OPA), specifically agglutinating human O erythrocytes
      and rabbit erythrocytes. The hemagglutination could be strongly inhibited by
      mannan and thyroglobulin, the activity of which was stable in pH range of 4.0-8.0
      and at temperatures below 50  degrees C. Chemical modification studies indicated
      that tryptophan and arginine residues were essential for its hemagglutinating
      activity. Meanwhile, it showed antifungal activities toward Sclerotium rolfsii
      and Fusarium graminearum. In addition, to amplify cDNA of OPA by 3'/5'-rapid
      amplification of cDNA ends (RACE), the N-terminal 30 amino acids sequence of OPA
      was determined, and degenerate primers were designed. The obtained full-length
      cDNA of OPA contained 885 bp with an open-reading frame of 600 bp encoding a
      precursor protein of 199 amino acids, while the mature protein had 170 amino
      acids.

PMID- 21947762
TI  - Influence of agitation speed on tannase production and morphology of Aspergillus
      niger FETL FT3 in submerged fermentation.
AB  - Agitation speed was found to influence the tannase production and fungal growth
      of Aspergillus niger FETL FT3. The optimal agitation speed was at 200 rpm which
      produced 1.41 U/ml tannase and 3.75 g/l of fungal growth. Lower or higher
      agitation speeds than 200 rpm produced lower enzyme production and fungal growth.
      Based on the SEM and TEM micrograph observation, there was a significant
      correlation between agitation speed and the morphology of the fungal mycelia. The
      results revealed an increase of the enzyme production with the change of the
      fungal growth morphology from filamentous to pelleted growth forms. However, the
      exposure to higher shear stress with an increasing agitation speed of the shaker
      also resulted in lower biomass yields as well as enzyme production.

PMID- 21947763
TI  - Screening and production of ligninolytic enzyme by a marine-derived fungal
      Pestalotiopsis sp. J63.
AB  - Marine-derived fungi are prone to produce structurally unique secondary
      metabolites, a considerable number of which display the promising biological
      properties and/or industrial applications. Among those, ligninolytic enzymes have
      attracted great interest in recent years. In this work, about 20 strains were
      isolated from sea mud samples collected in the East China Sea and then screened
      for their capacity to produce lignin-degrading enzymes. The results showed that a
      strain, named J63, had a great potential to secrete a considerable amount of
      laccase. Using molecular method, it was identified as an endophytic fungus,
      Pestalotiopsis sp. which was rarely reported as ligninolytic enzyme producer in
      the literature. The production of laccase by Pestalotiopsis sp. J63 was
      investigated under submerged fermentation (SF) and solid state fermentation (SSF)
      with various lignocellulosic by-products as substrates. The SSF of rice straw
      powder accumulated the highest level of laccase activity (10,700 IU/g substrate),
      whereas the SF of untreated sugarcane bagasse provided the maximum amount of
      laccase activity (2,000 IU/ml). The value was far higher than those reported by
      other reports. In addition, it produced 0.11 U/ml cellulase when alkaline
      pretreated sugarcane bagasse was used as growth substrate under SF. Meanwhile,
      the growth of fungi and laccase production under different salinity conditions
      were also studied. It appeared to be a moderately halo-tolerant organism.

PMID- 21947761
TI  - Theranostic applications of nanomaterials in cancer: drug delivery, image-guided
      therapy, and multifunctional platforms.
AB  - Successful cancer management depends on accurate diagnostics along with specific
      treatment protocols. Current diagnostic techniques need to be improved to provide
      earlier detection capabilities, and traditional chemotherapy approaches to cancer
      treatment are limited by lack of specificity and systemic toxicity. This review
      highlights advances in nanotechnology that have allowed the development of
      multifunctional platforms for cancer detection, therapy, and monitoring.
      Nanomaterials can be used as MRI, optical imaging, and photoacoustic imaging
      contrast agents. When used as drug carriers, nanoformulations can increase tumor
      exposure to therapeutic agents and result in improved treatment effects by
      prolonging circulation times, protecting entrapped drugs from degradation, and
      enhancing tumor uptake through the enhanced permeability and retention effect as
      well as receptor-mediated endocytosis. Multiple therapeutic agents such as
      chemotherapy, antiangiogenic, or gene therapy agents can be simultaneously
      delivered by nanocarriers to tumor sites to enhance the effectiveness of therapy.
      Additionally, imaging and therapy agents can be co-delivered to provide seamless
      integration of diagnostics, therapy, and follow-up, and different therapeutic
      modalities such as chemotherapy and hyperthermia can be co-administered to take
      advantage of synergistic effects. Liposomes, metallic nanoparticles, polymeric
      nanoparticles, dendrimers, carbon nanotubes, and quantum dots are examples of
      nanoformulations that can be used as multifunctional platforms for cancer
      theranostics. Nanomedicine approaches in cancer have great potential for
      clinically translatable advances that can positively impact the overall
      diagnostic and therapeutic process and result in enhanced quality of life for
      cancer patients. However, a concerted scientific effort is still necessary to
      fully explore long-term risks, effects, and precautions for safe human use.

PMID- 21947765
TI  - On cochlear impedances and the miscomputation of power gain.
AB  - In their article, "Measurement of cochlear power gain in the sensitive gerbil
      ear," Ren et al. (Nat Commun 2:216, 2011) claim to provide "the first direct
      experimental evidence of power amplification in the sensitive living cochlea."
      While we recognize the technical challenges of the experiments and appreciate the
      beauty of the data, the authors' analysis and interpretation of the measurements
      are invalid. We review the concept of impedance (i.e., the ratio of pressure to
      velocity) as it applies to cochlear mechanics and show that Ren et al. mistakenly
      equate the impedances near the basilar membrane and stapes with the impedance
      characteristic of an infinite, uniform tube of fluid. As a consequence of this
      error, Ren et al.'s measurements and analysis provide no evidence for power
      amplification in the cochlea. Compelling evidence for power amplification has,
      however, been previously provided by others.

PMID- 21947764
TI  - Mastitis: comparative etiology and epidemiology.
AB  - Mastitis is broadly defined as the inflammation of the mammary gland; however,
      the concept of mastitis is customized to address its social and clinical impact
      in the case of humans and the health, welfare, and economic consequences for
      other mammals. There are many microbial, host, and environmental factors that
      influence the development of mastitis. Some are common to all mammals as well as
      inherent to each species. Together these factors influence the most prevalent
      etiological agents for each species and might determine the possibility of
      interspecies transmission with its consequences to public health. The present
      review will summarize and compare reports on mastitis etiology and its
      epidemiology in humans and food animal species.

PMID- 21947766
TI  - Computer-assisted and patient-specific 3-D planning and evaluation of a single
      cut rotational osteotomy for complex long-bone deformities.
AB  - Malunion after long bone fracture results in an incorrect position of the distal
      bone segment. This misalignment may lead to reduced function of the limb, early
      osteoarthritis and chronic pain. An established treatment option is a corrective
      osteotomy. For complex malunions, a single-cut rotational osteotomy is sometimes
      preferred in cases of angular deformity in three dimensions. However, planning
      and performing this type of osteotomy is relatively complex. This report
      describes a computer-assisted method for 3-D planning and realizing a single-cut
      rotational osteotomy with a patient-specific cutting guide for orienting the
      osteotomy and an angled jig for adjusting the rotation angle. The accuracy and
      reproducibility of the method is evaluated experimentally using plastic bones. In
      addition, complex rotational deformities are simulated by a computer to
      investigate the relation between deformity and correction parameters. The
      computed relation between deformity and correction parameters enables the surgeon
      to judge the feasibility of a single-cut rotational osteotomy. This appears
      possible for deformities combining axial misalignment with sufficient axial
      rotation. The proposed 3-D method of preoperative planning and transfer with a
      patient-specific cutting guide and angled jig renders the osteotomy procedure
      easily applicable, accurate, reproducible, and is a good alternative for complex
      and expensive navigation systems.

PMID- 21947767
TI  - Mechanical and microarchitectural analyses of cancellous bone through experiment
      and computer simulation.
AB  - The relationship between microarchitecture to the failure mechanism and
      mechanical properties can be assessed through experimental and computational
      methods. In this study, both methods were utilised using bovine cadavers. Twenty
      four samples of cancellous bone were extracted from fresh bovine and the samples
      were cleaned from excessive marrow. Uniaxial compression testing was performed
      with displacement control. After mechanical testing, each specimen was ashed in a
      furnace. Four of the samples were exemplarily scanned using micro-computed
      tomography (MUCT) and three dimensional models of the cancellous bones were
      reconstructed for finite element simulation. The mechanical properties and the
      failure modes obtained from numerical simulations were then compared to the
      experiments. Correlations between microarchitectural parameters to the mechanical
      properties and failure modes were then made. The Young's modulus correlates well
      with the bone volume fraction with R2 = 0.615 and P value 0.013. Three different
      types of failure modes of cancellous bone were observed: oblique fracture
      (21.7%), perpendicular global fracture (47.8%), and scattered localised fracture
      (30.4%). However, no correlations were found between the failure modes to the
      morphological parameters. The percentage of error between computer predictions
      and the actual experimental test was from 6 to 12%. These mechanical properties
      and information on failure modes can be used for the development of synthetic
      cancellous bone.

PMID- 21947768
TI  - Apo a-I modulating therapies.
AB  - The substantial residual risk of cardiovascular events despite the implementation
      of effective lowering of low-density lipoprotein cholesterol highlights the need
      to develop additional cardioprotective therapies. Evidence from population and
      animal studies suggests that high-density lipoproteins (HDLs), the protective
      lipid particles, may represent a target for therapeutic modification. As a result
      intensive efforts are in progress to develop new agents that promote HDL
      activity. Among these different approaches, a range of strategies that target
      apolipoprotein A-I, the major protein carried on HDL, are being evaluated.

PMID- 21947769
TI  - Mycobacterium tuberculosis Hip1 dampens macrophage proinflammatory responses by
      limiting toll-like receptor 2 activation.
AB  - Mycobacterium tuberculosis is a highly successful human pathogen that evades host
      innate immunity by interfering with macrophage functions. In addition to avoiding
      macrophage microbicidal activities, M. tuberculosis triggers secretion of
      proinflammatory cytokines and chemokines in macrophages. The levels of
      proinflammatory cytokines induced by clinical M. tuberculosis isolates are
      thought to play an important role in determining tuberculosis disease progression
      and severity, but the mechanisms by which M. tuberculosis modulates the magnitude
      of inflammatory responses remain unclear. Here we show that M. tuberculosis
      restricts robust macrophage activation and dampens proinflammatory responses
      through the cell envelope-associated serine hydrolase Hip1 (hydrolase important
      for pathogenesis 1). By transcriptionally profiling macrophages infected with
      either wild-type or hip1 mutant bacteria, we found that the hip1 mutant induced
      earlier and significantly higher levels of several proinflammatory cytokines and
      chemokines. We show that increased activation of Toll-like receptor 2 (TLR2)- and
      MyD88-dependent signaling pathways mediates the enhanced cytokine secretion
      induced by the hip1 mutant. Thus, Hip1 restricts the onset and magnitude of
      proinflammatory cytokines by limiting TLR2-dependent activation. We also show
      that Hip1 dampens TLR2-independent activation of the inflammasome and limits
      secretion of interleukin-18 (IL-18). Dampening of TLR2 signaling does not require
      viable M. tuberculosis or phagocytosis but does require Hip1 catalytic activity.
      We propose that M. tuberculosis restricts proinflammatory responses by masking
      cell surface interactions between TLR2 agonists on M. tuberculosis and TLR2 on
      macrophages. This strategy may allow M. tuberculosis to evade early detection by
      host immunity, delay the onset of adaptive immune responses, and accelerate
      disease progression.

PMID- 21947771
TI  - Toll-like receptor 9 modulates macrophage antifungal effector function during
      innate recognition of Candida albicans and Saccharomyces cerevisiae.
AB  - Phagocytic responses are critical for effective host defense against
      opportunistic fungal pathogens. Macrophages sample the phagosomal content and
      orchestrate the innate immune response. Toll-like receptor 9 (TLR9) recognizes
      unmethylated CpG DNA and is activated by fungal DNA. Here we demonstrate that
      specific triggering of TLR9 recruitment to the macrophage phagosomal membrane is
      a conserved feature of fungi of distinct phylogenetic origins, including Candida
      albicans, Saccharomyces cerevisiae, Malassezia furfur, and Cryptococcus
      neoformans. The capacity to trigger phagosomal TLR9 recruitment was not affected
      by a loss of fungal viability or cell wall integrity. TLR9 deficiency has been
      linked to increased resistance to murine candidiasis and to restriction of fungal
      growth in vivo. Macrophages lacking TLR9 demonstrate a comparable capacity for
      phagocytosis and normal phagosomal maturation compared to wild-type macrophages.
      We now show that TLR9 deficiency increases macrophage tumor necrosis factor alpha
      (TNF-alpha) production in response to C. albicans and S. cerevisiae, independent
      of yeast viability. The increase in TNF-alpha production was reversible by
      functional complementation of the TLR9 gene, confirming that TLR9 was responsible
      for negative modulation of the cytokine response. Consistently, TLR9 deficiency
      enhanced the macrophage effector response by increasing macrophage nitric oxide
      production. Moreover, microbicidal activity against C. albicans and S. cerevisiae
      was more efficient in TLR9 knockout (TLR9KO) macrophages than in wild-type
      macrophages. In conclusion, our data demonstrate that TLR9 is compartmentalized
      selectively to fungal phagosomes and negatively modulates macrophage antifungal
      effector functions. Our data support a model in which orchestration of antifungal
      innate immunity involves a complex interplay of fungal ligand combinations, host
      cell machinery rearrangements, and TLR cooperation and antagonism.

PMID- 21947770
TI  - The iron-repressed, AraC-like regulator MpeR activates expression of fetA in
      Neisseria gonorrhoeae.
AB  - Neisseria gonorrhoeae is an obligate human pathogen that causes the common
      sexually transmitted infection gonorrhea. Gonococcal infections cause significant
      morbidity, particularly among women, as the organism ascends to the upper
      reproductive tract, resulting in pelvic inflammatory disease, ectopic pregnancy,
      and infertility. In the last few years, antibiotic resistance rates have risen
      dramatically, leading to severe restriction of treatment options for gonococcal
      disease. Gonococcal infections do not elicit protective immunity, nor is there an
      effective vaccine to prevent the disease. Thus, further understanding of the
      expression, function, and regulation of surface antigens could lead to better
      treatment and prevention modalities in the future. In the current study, we
      determined that an iron-repressed regulator, MpeR, interacted specifically with
      the DNA sequence upstream of fetA and activated FetA expression. Interestingly,
      MpeR was previously shown to regulate the expression of gonococcal antimicrobial
      efflux systems. We confirmed that the outer membrane transporter FetA allows
      gonococcal strain FA1090 to utilize the xenosiderophore ferric enterobactin as an
      iron source. However, we further demonstrated that FetA has an extended range of
      substrates that encompasses other catecholate xenosiderophores, including ferric
      salmochelin and the dimers and trimers of dihydroxybenzoylserine. We demonstrated
      that fetA is part of an iron-repressed, MpeR-activated operon which putatively
      encodes other iron transport proteins. This is the first study to describe a
      regulatory linkage between antimicrobial efflux and iron transport in N.
      gonorrhoeae. The regulatory nidus that links these systems, MpeR, is expressed
      exclusively by pathogenic neisseriae and is therefore expected to be an important
      virulence factor.

PMID- 21947772
TI  - Suppression of the inflammatory immune response prevents the development of
      chronic biofilm infection due to methicillin-resistant Staphylococcus aureus.
AB  - Staphylococcus aureus is a common cause of prosthetic implant infections, which
      can become chronic due to the ability of S. aureus to grow as a biofilm. Little
      is known about adaptive immune responses to these infections in vivo. We
      hypothesized that S. aureus elicits inflammatory Th1/Th17 responses, associated
      with biofilm formation, instead of protective Th2/Treg responses. We used an
      adapted mouse model of biofilm-mediated prosthetic implant infection to determine
      chronic infection rates, Treg cell frequencies, and local cytokine levels in Th1
      biased C57BL/6 and Th2-biased BALB/c mice. All C57BL/6 mice developed chronic S.
      aureus implant infection at all time points tested. However, over 75% of BALB/c
      mice spontaneously cleared the infection without adjunctive therapy and
      demonstrated higher levels of Th2 cytokines and anti-inflammatory Treg cells.
      When chronic infection rates in mice deficient in the Th2 cytokine interleukin-4
      (IL-4) via STAT6 mutation in a BALB/c background were assessed, the mice were
      unable to clear the S. aureus implant infection. Additionally, BALB/c mice
      depleted of Treg cells via an anti-CD25 monoclonal antibody (MAb) were also
      unable to clear the infection. In contrast, the C57BL/6 mice that were
      susceptible to infection were able to eliminate S. aureus biofilm populations on
      infected intramedullary pins once the Th1 and Th17 responses were diminished by
      MAb treatment with anti-IL-12 p40. Together, these results indicate that Th2/Treg
      responses are mechanisms of protection against chronic S. aureus implant
      infection, as opposed to Th1/Th17 responses, which may play a role in the
      development of chronic infection.

PMID- 21947773
TI  - Interleukin-10 alters effector functions of multiple genes induced by Borrelia
      burgdorferi in macrophages to regulate Lyme disease inflammation.
AB  - Interleukin-10 (IL-10) modulates inflammatory responses elicited in vitro and in
      vivo by Borrelia burgdorferi, the Lyme disease spirochete. How IL-10 modulates
      these inflammatory responses still remains elusive. We hypothesize that IL-10
      inhibits effector functions of multiple genes induced by B. burgdorferi in
      macrophages to control concomitantly elicited inflammation. Because macrophages
      are essential in the initiation of inflammation, we used mouse J774 macrophages
      and live B. burgdorferi spirochetes as the model target cell and stimulant,
      respectively. First, we employed transcriptome profiling to identify genes that
      were induced by stimulation of cells with live spirochetes and that were
      perturbed by addition of IL-10 to spirochete cultures. Spirochetes significantly
      induced upregulation of 347 genes at both the 4-h and 24-h time points. IL-10
      inhibited the expression levels, respectively, of 53 and 65 of the 4-h and 24-h
      genes, and potentiated, respectively, at 4 h and 24 h, 65 and 50 genes. Prominent
      among the novel identified IL-10-inhibited genes also validated by quantitative
      real-time PCR (qRT-PCR) were Toll-like receptor 1 (TLR1), TLR2, IRAK3, TRAF1,
      IRG1, PTGS2, MMP9, IFI44, IFIT1, and CD40. Proteome analysis using a multiplex
      enzyme-linked immunosorbent assay (ELISA) revealed the IL-10 modulation/and or
      potentiation of RANTES/CCL5, macrophage inflammatory protein 2 (MIP-2)/CXCL2, IP
      10/CXCL10, MIP-1alpha/CCL3, granulocyte colony-stimulating factor (G-CSF)/CSF3,
      CXCL1, CXCL5, CCL2, CCL4, IL-6, tumor necrosis factor alpha (TNF-alpha), IL
      1alpha, IL-1beta, gamma interferon (IFN-gamma), and IL-9. Similar results were
      obtained using sonicated spirochetes or lipoprotein as stimulants. Our data show
      that IL-10 alters effectors induced by B. burgdorferi in macrophages to control
      concomitantly elicited inflammatory responses. Moreover, for the first time, this
      study provides global insight into potential mechanisms used by IL-10 to control
      Lyme disease inflammation.

PMID- 21947774
TI  - Infection with conditionally virulent Streptococcus pneumoniae Deltapab strains
      induces antibody to conserved protein antigens but does not protect against
      systemic infection with heterologous strains.
AB  - Avirulent strains of a bacterial pathogen could be useful tools for investigating
      immunological responses to infection and potentially effective vaccines. We have
      therefore constructed an auxotrophic TIGR4 Deltapab strain of Streptococcus
      pneumoniae by deleting the pabB gene Sp_0665. The TIGR4 Deltapab strain grew well
      in complete medium but was unable to grow in serum unless it was supplemented
      with para-aminobenzoic acid (PABA). The TIGR4 Deltapab strain was markedly
      attenuated in virulence in mouse models of S. pneumoniae nasopharyngeal
      colonization, pneumonia, and sepsis. Supplementing mouse drinking water with PABA
      largely restored the virulence of TIGR4 Deltapab. An additional Deltapab strain
      constructed in the D39 capsular serotype 2 background was also avirulent in a
      sepsis model. Systemic inoculation of mice with TIGR4 Deltapab induced antibody
      responses to S. pneumoniae protein antigens, including PpmA, PsaA, pneumolysin,
      and CbpD, but not capsular polysaccharide. Flow cytometry demonstrated that IgG
      in sera from TIGR4 Deltapab-vaccinated mice bound to the surface of TIGR4 and D39
      bacteria but not to a capsular serotype 3 strain, strain 0100993. Mice vaccinated
      with the TIGR4 Deltapab or D39 Deltapab strain by intraperitoneal inoculation
      were protected from developing septicemia when challenged with the homologous S.
      pneumoniae strain. Vaccination with the TIGR4 Deltapab strain provided only weak
      or no protection against heterologous challenge with the D39 or 0100993 strain
      but did strongly protect against a TIGR4 capsular-switch strain expressing a
      serotype 2 capsule. The failure of cross-protection after systemic vaccination
      with Deltapab bacteria suggests that parenteral administration of a live
      attenuated vaccine is not an attractive approach for preventing S. pneumoniae
      infection.

PMID- 21947775
TI  - Production of autoantibodies by murine B-1a cells stimulated with Helicobacter
      pylori urease through toll-like receptor 2 signaling.
AB  - Helicobacter pylori infection is associated with several autoimmune diseases, in
      which autoantibody-producing B cells must be activated. Among these B cells, CD5
      positive B-1a cells from BALB/c mice were confirmed to secrete autoantibodies
      when cocultured with purified H. pylori urease in the absence of T cells. To
      determine the mechanisms for autoantibody production, CD5-positive B-1a cells
      were sorted from murine spleen cells and stimulated with either purified H.
      pylori urease or H. pylori coated onto plates (referred to hereafter as plate
      coated H. pylori), and autoantibody production was measured by enzyme-linked
      immunosorbent assay (ELISA). Complete urease was not secreted from H. pylori but
      was visually expressed over the bacterium-like endotoxin. Urease-positive plated
      coated H. pylori stimulated B-1a cells to produce autoantibodies, although urease
      deficient isotype-matched H. pylori did not. Autoantibody secretion by B-1a cells
      was inhibited when bacteria were pretreated with anti-H. pylori urease-specific
      antibody having neutralizing ability against urease enzymatic activity but not
      with anti-H. pylori urease-specific antibody without neutralizing capacity. The B
      1a cells externally express various Toll-like receptors (TLRs): TLR1, TLR2, TLR4,
      and TLR6. Among the TLRs, blocking of TLR2 on B-1a cells with a specific
      monoclonal antibody (MAb), T2.5, inhibited autoantibody secretion when B-1a cells
      were stimulated with plate-coated H. pylori or H. pylori urease. Moreover, B-1a
      cells from TLR2-knockout mice did not produce those autoantibodies. The present
      study provides evidence that functional urease expressed on the surface of H.
      pylori will directly stimulate B-1a cells via innate TLR2 to produce various
      autoantibodies and may induce autoimmune disorders.

PMID- 21947776
TI  - Surface-affinity profiling to identify host-pathogen interactions.
AB  - Proteolytic treatment of intact bacterial cells has proven to be a convenient
      approach for the identification of surface-exposed proteins. This class of
      proteins directly interacts with the outside world, for instance, during
      adherence to human epithelial cells. Here, we aimed to identify host receptor
      proteins by introducing a preincubation step in which bacterial cells were first
      allowed to capture human proteins from epithelial cell lysates. Using
      Streptococcus gallolyticus as a model bacterium, liquid chromatography-tandem
      mass spectrometry (LC-MS/MS) analysis of proteolytically released peptides
      yielded the identification of a selective number of human epithelial proteins
      that were retained by the bacterial surface. Of these potential receptors for
      bacterial interference, (cyto)keratin-8 (CK8) was verified as the most
      significant hit, and its surface localization was investigated by subcellular
      fractionation and confocal microscopy. Interestingly, bacterial enolase could be
      assigned as an interaction partner of CK8 by MS/MS analysis of cross-linked
      protein complexes and complementary immunoblotting experiments. As surface
      exposed enolase has a proposed role in epithelial adherence of several Gram
      positive pathogens, its interaction with CK8 seems to point toward a more general
      virulence mechanism. In conclusion, our study shows that surface-affinity
      profiling is a valuable tool to identify novel adhesin-receptor pairs, which
      advocates its application in other hybrid biological systems.

PMID- 21947777
TI  - The type III system-secreted effector EspZ localizes to host mitochondria and
      interacts with the translocase of inner mitochondrial membrane 17b.
AB  - Enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC,
      respectively) are attaching and effacing (A/E) bacterial pathogens that cause
      severe diarrheal disease worldwide. To cause disease, A/E pathogens require a
      type III secretion system, which facilitates transport of bacterial effector
      proteins directly into infected host cells. One of these effector proteins
      translocated by the type III secretion system, EspZ, is essential for A/E
      pathogen infection and functions to prevent rapid death of EPEC-infected cells.
      We further investigated the mechanism of EspZ-mediated protection of infected
      host cells and found that a severe decrease in host mitochondrial membrane
      potential (Deltapsi(m)) occurs concurrently with host cell lysis during infection
      with EPEC lacking EspZ (DeltaespZ). It was also demonstrated that EspZ localizes
      to host cell mitochondria and interacts with the translocase of inner
      mitochondrial membrane 17b (TIM17b). In addition, host cell cytotoxicity was
      exacerbated in the absence of TIM17b during wild-type (WT) EPEC infection. The
      findings of this study together provide the first evidence that EspZ localizes to
      host mitochondria and that TIM17b contributes to protection against rapid cell
      death during EPEC infection.

PMID- 21947778
TI  - Associations of pregnancy characteristics with maternal and cord steroid
      hormones, angiogenic factors, and insulin-like growth factor axis.
AB  - BACKGROUND: The objective of this study was to comprehensively profile biological
      factors in pregnancy that have been postulated to be important components of the
      in utero environment and may also have relevance to later susceptibility to
      cancer and other chronic diseases. METHODS: Steroid sex hormones, IGFs, and
      angiogenic factors were measured in maternal and cord serum from term
      normotensive pregnancies. Spearman correlations and linear regression estimated
      relationships among the biological factors and clinical characteristics. RESULTS:
      The analytes were generally not correlated between maternal and fetal
      circulations. However, significant correlations were demonstrated among several
      analytes within maternal or cord samples. A few analytes were associated with
      clinical characteristics (e.g., maternal IGF-1 and IGFBP-3 were inversely
      correlated with offspring birth weight, while maternal leptin and cord
      testosterone were positively correlated with this characteristic). Maternal
      androgens were higher in African-Americans than whites, and maternal PlGF and
      soluble fms-like tyrosine kinase-1 (sFlt-1) were higher in male than female
      offspring. CONCLUSIONS: There were significant correlations among analytes, but
      the patterns differed depending on whether they were measured in the maternal or
      fetal circulation. The number and magnitude of correlations among analytes,
      however, should affect the design and interpretation of future studies.

PMID- 21947779
TI  - Similar taxonomic richness but different communities of ectomycorrhizas in native
      forests and non-native plantation forests.
AB  - This investigation sought to examine if there was a difference between the
      ectomycorrhizal (ECM) communities in plots of native oak and introduced Scots
      pine and Sitka spruce forest. The ECM communities in four plots of each forest
      type were described, from five soil cores collected in each plot, by
      morphotyping, internal transcribed spacer (ITS)-restriction fragment length
      polymorphism matching of mycorrhizas and sporocarps and ITS sequencing. Fifty-one
      distinct taxa were distinguished; 25 were identified to species level, 11 to
      genus and 15 remained unidentified. Seventy-one ECM species were recorded as
      sporocarps from the forest plots; most (43 species) were found in the Sitka
      spruce plots. The below-ground ECM communities of the different forest types did
      not differ significantly with respect to species richness of taxa on roots, but
      differed in species composition. Multivariate analysis produced a clear
      separation of the communities of the different forest types using below-ground
      data, but the above-ground sporocarp data did not separate the forest types.
      Moreover, results of a Mantel test found no relationship between the above- and
      below-ground similarity matrices. The oak plots had the most distinctive ECM
      community, with Laccaria amethystina and Elaphomyces granulatus being frequent.
      The Sitka spruce plots showed the lowest intra-forest type similarity and were
      often dominated by "nursery type" ectomycorrhizas. There was only 10% similarity
      between the above- and below-ground ECM species in these plots, different
      colonisation methods of ectomycorrhizal taxa and insufficient below-ground
      sampling being possible reasons for this disparity. Our results indicate that
      plantations of non-native Sitka spruce can support similar levels of ECM
      diversity as native forests.

PMID- 21947780
TI  - Interest in, concerns about, and preferences for potential video-group delivery
      of an effective behavioral intervention among women living with HIV.
AB  - Novel strategies are needed to expand access to effective behavioral
      interventions for HIV prevention. Delivering effective group-based interventions
      to people living with HIV using video-conferencing technology is an innovative
      approach that may address this need, but has not been explored. Twenty-seven
      women living with HIV (WLH) who had just completed Healthy Relationships, a group
      based behavioral program for WLH, participated in focus groups to share their
      thoughts about potentially participating in Healthy Relationships via a video
      conferencing group. Overall, WLH supported the idea of video-group delivery of
      the program. They had numerous questions about logistics, expressed concerns
      about safety and confidentiality, and indicated a preference for accessing video
      groups via special video-phones versus computers. Findings warrant further
      research into the feasibility, acceptability, and effectiveness of video-group
      delivery of HIV prevention interventions and suggest important considerations for
      researchers and practitioners who may employ video-conferencing for intervention
      delivery.

PMID- 21947781
TI  - Assessment of fluoride-induced changes on physicochemical and structural
      properties of bone and the impact of calcium on its control in rabbits.
AB  - Bone deformities caused by the chronic intake of large quantities of fluoride and
      the beneficial effect of calcium on its control have been studied for many years,
      but only limited data are available on the quantitative effect of fluoride intake
      and the beneficial impact of calcium on fluoride-induced changes in bone at the
      molecular level. It is necessary to determine the degree of fluoride-induced
      changes in bone at different levels of fluoride intake to evaluate the optimum
      safe intake level of fluoride for maintaining bone health and quality. The
      ameliorative effect of calcium at different dose levels on minimizing fluoride
      induced changes in bone is important to quantify the amount of calcium intake
      necessary for reducing fluoride toxicity. Thirty rabbits, 2 months old, were
      divided into five groups. Group I animals received 1 mg/l fluoride and 0.11%
      calcium diet; groups II and III received 10 mg/l fluoride and diet with 0.11% or
      2.11% calcium, respectively; and groups IV and V received 150 mg/l fluoride and
      diet with 2.11% or 0.11% calcium, respectively. Analysis of bone density, ash
      content, fluoride, calcium, phosphorus, and Ca:P molar ratio levels after 6
      months of treatment indicated that animals that received high fluoride with low
      calcium diet showed significant detrimental changes in physicochemical properties
      of bone. Animals that received fluoride with high calcium intake showed notable
      amelioration of the impact of calcium on fluoride-induced changes in bone. The
      degree of fluoride-induced characteristic changes in structural properties such
      as crystalline size, crystallinity, and crystallographic "c"-axis length of bone
      apatite cells was also assessed by X-ray diffraction and Fourier transform
      infrared studies. X-ray images showed bone deformity changes such as transverse
      stress growth lines, soft tissue ossification, and calcification in different
      parts of bones as a result of high fluoride accumulation and the beneficial role
      of calcium intake on its control.

PMID- 21947782
TI  - Overexpression of receptor for hyaluronan-mediated motility (RHAMM) in MC3T3-E1
      cells induces proliferation and differentiation through phosphorylation of
      ERK1/2.
AB  - Receptor for hyaluronan (HA)-mediated motility (RHAMM) was first described as a
      soluble HA binding protein released by sub-confluent migrating cells. We
      previously found that RHAMM was highly expressed and plays an important role in
      proliferation in the human cementifying fibroma (HCF) cell line, which we
      previously established. HCF is a benign fibro-osseous neoplasm of the jaw and is
      composed of fibrous tissue containing varying amounts of mineralized material.
      However, the pathogenesis of HCF is not clear. In this paper, we examined the
      roles of RHAMM in osteoblastic cells. We generated RHAMM-overexpressing MC3T3-E1
      cells and examined the cell proliferation and differentiation of osteoblastic
      cells. In MC3T3-E1 cells, overexpressing RHAMM was located intracellular and
      activated ERK1/2. Interestingly, the ERK1/2 activated by RHAMM overexpression
      promoted cell proliferation and suppressed the differentiation of osteoblastic
      cells. Our findings strongly suggest that RHAMM may play a key role in the
      osteoblastic differentiation process. The rupture of balance from differentiation
      to proliferation induced by RHAMM overexpression may link to the pathogenesis of
      bone neoplasms such as HCF.

PMID- 21947783
TI  - The virulence gene and clinical phenotypes of osteopetrosis in the Chinese
      population: six novel mutations of the CLCN7 gene in twelve osteopetrosis
      families.
AB  - Osteopetrosis is a heritable bone disorder resulting from a deficiency of or a
      functional defect in osteoclasts. We aimed to characterize the molecular defects
      and clinical manifestations in Chinese patients with osteopetrosis by studying 12
      unrelated osteopetrosis families. The entire coding region and adjacent splice
      sites of the CLCN7, TCIRG1, LRP5 and SOST genes were amplified and directly
      sequenced. X-rays of hip and lumbar spine, bone mineral density and bone turnover
      markers were examined simultaneously. Family history and fracture history were
      collected using a questionnaire. Among 12 unrelated families, 10 families were
      diagnosed with autosomal dominant osteopetrosis type II (ADOII) with 10 probands
      and 3 affected subjects. Two individuals in the other two families were diagnosed
      with uncategorized osteopetrosis because no mutations were detected in any of the
      four studied genes. Eight mutations, including two reported mutations (R767W and
      E798FS) and six novel mutations (E313K, A316G, R743W, G741R, W127G and S290F),
      were detected in the CLCN7 gene from 12 living ADOII patients. Among them, R767W
      and R743W mutations were two common mutations that were each found in 20% of 10
      ADOII probands. In CLCN7-related ADOII patients, long bone fractures and elevated
      serum CK level were two major clinical phenotypes, especially in patients younger
      than 18 years. Further functional studies of the above eight mutations in the
      CLCN7 gene are needed in the future.

PMID- 21947784
TI  - Utilization of PVX-Cre expression vector in potato.
AB  - Trait genes are usually introduced into the plant genome together with a marker
      gene. The last one becomes unnecessary after transgene selection and
      characterization. One of the strategies to produce transgenic plants free from
      the selectable marker is based on site-specific recombination. The present study
      employed the transient Cre-lox system to remove the nptII marker gene from
      potato. Transient marker gene excision involves introduction of Cre protein in
      lox-target plants by PVX virus vector followed by plant regeneration. Using
      optimized experimental conditions, such as particle bombardment infection method
      and application of P19 silencing suppressor protein, 20-27% of regenerated plants
      were identified by PCR analysis as marker-free. Based on our comparison of the
      recombination frequencies observed in this study to the efficiency of other
      methods to avoid or eliminate marker genes in potato, we suggest that PVX-Cre
      mediated site-specific excisional recombination is a useful tool to generate
      potato plants without superfluous transgenic sequences.

PMID- 21947786
TI  - Incomplete occlusion of the left atrial appendage with the percutaneous left
      atrial appendage transcatheter occlusion device is not associated with increased
      risk of stroke.
AB  - BACKGROUND: Percutaneous approaches to left atrial appendage (LAA) closure are
      being developed for stroke prophylaxis in atrial fibrillation patients as an
      alternative to warfarin. Non-randomized clinical trials suggested that the first
      of these devices, the percutaneous left atrial appendage transcatheter occlusion
      (PLAATO) device, is safe and reduces stroke risk. Percutaneous closure has the
      potential limitation of incomplete exclusion of LAA from the systemic
      circulation, which could potentially lead to thrombus formation and stroke. This
      study investigated the interaction between residual blood flow in the LAA after
      percutaneous closure with PLAATO and risk of stroke. METHODS AND RESULTS: Data
      from the PLAATO trial current as of July 2010 was used for this analysis (n =
      22). Mechanical occlusion using the PLAATO device was used in 22 patients (age 68
      +/- 5, CHADS(2) score = 3.03 +/- 0.6). Warfarin and clopidogrel were stopped
      during follow-up in all but one patient due to development of pulmonary emboli.
      After an average follow-up of 58 +/- 9 months, four out of 22 patients (16.7%)
      developed a new ischemic stroke/TIA, translating to an annualized embolic rate of
      3.63%. There were no differences in the demographics (age, sex, and CHADS(2)
      score) among patients with and without stroke. Cardiac CT documented peri-device
      leak in three out of four patients with stroke and in seven out of nine (75% vs.
      77%, p = 0.706) patients without stroke that agreed to have a follow-up cardiac
      CT (Chi squared with Yates correction for this interaction = 0.012, p = 0.912).
      TEE corroborated these results but failed to identify peri-device leak in three
      patients without stroke. CONCLUSIONS: The main finding of our analysis suggests
      that in long-term follow-up, residual flow after LAA occlusion with the PLAATO
      device, as documented by cardiac CT, is ubiquitous but is not associated with an
      increased risk of stroke.

PMID- 21947785
TI  - Ascochlorin suppresses TGF-beta1-induced PAI-1 expression through the inhibition
      of phospho-EGFR in rat kidney fibroblast cells.
AB  - Fibrosis is induced by the excessive and abnormal deposition of extracellular
      matrix (ECM) with various growth factors in tissues. Transforming growth factor
      beta1 (TGF-beta1), the growth factor involved in fibrosis, modulates ECM
      synthesis and accumulation. TGF-beta1 enhances the production of stimulators of
      ECM synthesis such as plasminogen activator inhibitor type 1 (PAI-1). As such,
      PAI-1 expression directly influences the proteolysis, invasion, and accumulation
      of ECM. It was shown in this study that ascochlorin, a prenylpenl antiobiotic,
      prevents the expression of profibrotic factors, such as PAI-1 and collagen type
      I, and that the TGF-beta1-induced PAI-1 promoter activity is inhibited by
      ascochlorin. Ascochlorin abolishes the phosphorylation of the EGFR-MEK-ERK
      signaling pathway to regulate the TGF-beta1-induced expression of PAI-1 without
      the inhibition of TbetaRII phosphorylation. Furthermore, the MEK inhibitor and
      EGFR siRNA block PAI-1 expression, and the Raf-1, MEK, and ERK signaling pathways
      for the regulation of PAI-1 expression. Ascochlorin suppresses the matrix
      metalloproteinases (MMPs) activity to activate the heparin-binding EGF-like
      growth factor (HB-EGF), to induce the phosphorylation of EGFR, and the MMPs
      inhibitor suppresses EGFR phosphorylation and the PAI-1 mRNA levels. These
      results suggest that ascochlorin prevents the expression of PAI-1 via the
      inhibition of an EGFR-dependent signal transduction pathway activated by MMPs.

PMID- 21947787
TI  - Left ventricular pacing should be considered when biventricular pacing worsens
      heart failure: left ventricular pacing instead of biventricular pacing?

PMID- 21947788
TI  - Pacemaker implantation in the extreme elderly.
AB  - INTRODUCTION: There are scant data for pacemaker implant complications and
      readmission rates in the extreme elderly (age >=80 years) despite their common
      use in this population. METHODS: This is a retrospective chart review of
      consecutive patients (n = 149, age >=80 years) who underwent pacemaker
      implantation at a community hospital electrophysiology program from July 2008
      through June 2010. Single-, dual-, and biventricular-chamber pacemakers and
      generator changes were included for analysis; cardioverter-defibrillator devices,
      temporary pacemakers, and loop recorders were excluded. Standard procedures for
      implantation were used. Major complications were defined as death, cardiac
      arrest, cardiac perforation, cardiac valve injury, coronary venous dissection,
      hemothorax, pneumothorax, transient ischemic attack, stroke, myocardial
      infarction, pericardial tamponade, and arteriovenous fistula. Minor complications
      were defined as drug reaction, conduction block, hematoma or lead dislodgement
      requiring reoperation, peripheral embolus, phlebitis, peripheral nerve injury,
      and device-related infection. RESULTS: The overall mean age of implantation was
      86 years. There were no intraprocedural complications. There was one major in
      hospital complication (0.7%) and one minor in-hospital complication (0.7%).
      Within 30 days of implantation, there was an overall 5.4% rate of complications;
      four minor (2.7%) and four major (2.7%). There was a 30-day cardiovascular
      attributable mortality of 0.7% and an all-cause mortality of 2%. There was a 5.4%
      rate of readmission within 30 days of implantation. CONCLUSIONS: This report of
      pacemaker implantations in the extreme elderly reveals rates of implant
      complications comparable to data from younger patient populations while
      experiencing a higher 30-day all-cause mortality (that may be attributable to
      elevated all-cause mortality rates in this age group).

PMID- 21947789
TI  - Predictors of statin adherence.
AB  - Statin therapy plays a central role in decreasing the morbidity and mortality
      associated with cardiovascular disease. However, prescribed statins are only
      effective if they are taken by patients on a regular basis, known as medication
      adherence. The factors that influence patient adherence to statin therapy can be
      categorized into patient factors, physician factors, and health system factors,
      often with interactions between the categories. Patient factors include
      demographics, socioeconomic status, comorbidities, and side effects. Physician
      factors include the physician's own adherence to applying guideline
      recommendations, office visits, and their interactions with patients. Health
      system factors include issues such as cost and access to care. Physicians should
      be aware of the various elements that may influence a patient's likelihood to
      take statin medications to improve adherence and provide the best possible
      patient outcomes.

PMID- 21947790
TI  - Prognostic value of haemoglobin A1c and fasting plasma glucose for incident
      diabetes and implications for screening.
AB  - The aim of this analysis is to compare screening strategies with haemoglobin
      A(1c) (HbA(1c)), fasting plasma glucose (FPG) or combined measures in the
      identification of individuals at high risk for diabetes. Applying American
      Diabetes Association thresholds for FPG and HbA(1c) screening, 6,803 subjects
      free of diabetes were classified as non-diabetic, pre-diabetic and possibly
      diabetic by FPG (<100, 100-125 and >125 mg/dl) and HbA(1c) (<5.7, 5.7-6.4 and
      >6.4%). Hazard ratios, sensitivity and specificity were estimated for individuals
      with pre-diabetes with respect to incident diabetes in the following 5 years.
      Areas under the receiver operating characteristic curves (AUC) were estimated for
      levels of FPG <= 125 mg/dl and HbA(1c) <= 6.4% in diabetes prediction. Although
      FPG and HbA(1c) screenings poorly agreed in classifying individuals as pre
      diabetic, hazard ratios [95% confidence interval] for incident diabetes were
      similarly increased in univariate models in the two pre-diabetic groups: FPG 100
      125 mg/dl, 4.72 [3.69; 6.05]; HbA(1c) 5.7-6.4%, 3.97 [3.05; 5.23]. HbA(1c) and
      FPG had comparable AUCs (FPG, 0.732; HbA(1c), 0.725) and consequently similar 5
      year sensitivities and specificities for their pre-diabetes definitions (when the
      lower cut-off for HbA(1c)-defined pre-diabetes was increased to a level between
      5.8 and 5.9%). Combining HbA(1c) and FPG increased the AUC to 0.778, and a
      further increase to 0.817 was seen with additional inclusion of conventional risk
      factors. FPG and HbA(1c) have comparable (yet insufficient) abilities in
      identifying individuals at high risk for diabetes. Effectiveness of a diabetes
      screening program could be improved by a risk score including FPG and HbA(1c).

PMID- 21947791
TI  - Repair of nasal septal perforations using conjugate polydioxanone plate and
      autologous cartilage interpositional grafts.

PMID- 21947793
TI  - Dietary magnesium sulfate supplementation protects heat stress-induced oxidative
      damage by restoring the activities of anti-oxidative enzymes in broilers.
AB  - The purpose of this study was to investigate the effect of dietary magnesium
      sulfate supplementation on heat stress-induced oxidative damage in broilers. One
      hundred twenty 14-day-old broilers were randomly assigned into four treatment
      groups with three replicates of ten birds each. The broilers were reared under
      normal ambient temperature (24 +/- 1 degrees C) fed with a basal (control) diet
      or reared under high ambient temperature (35 +/- 1 degrees C between 1000 and
      1800 h, 8 h each day) fed with a basal diet supplemented with magnesium sulfate
      (0, 2.5 or 5.0 mg/kg of diet) from 14 to 42 days of age. Growth performance and
      oxidative damage were evaluated in each treatment group. Our results demonstrated
      that dietary magnesium sulfate supplementation significantly prevented heat
      stress-induced oxidative damage and improved growth performance in broilers
      compared with that of control. Mechanistically, this beneficial effect was
      mediated, at least partly, by restoring the activity of anti-oxidative enzymes.
      This finding suggests that magnesium sulfate supplementation might be a potential
      strategy to attenuate heat stress-induced detrimental effects in broilers raised
      in summer season or tropical areas.

PMID- 21947792
TI  - Role of stromal cell-derived factor-1 expression in the injured mouse auditory
      nerve.
AB  - OBJECTIVE: The degeneration of hair cells and spiral ganglion neurons (SGNs) is
      an important pathologic process in the development of sensorineural hearing loss.
      In a murine model, predictable and reproducible damage to SGNs occurs through the
      application of ouabain to the round window. Recent evidence has shown that the
      chemokine stromal cell-derived factor-1 (SDF-1) is a potent chemoattractant of
      hematopoietic stem cells (HSCs) and provides trophic support to injured tissues
      during development and maturation. The hypothesis for the current study is that
      expression of SDF-1 plays an important role in protecting SGNs and preventing
      further degeneration in the setting of cochlear injury. STUDY DESIGN:
      Prospective, controlled. SETTING: Academic research laboratory. SUBJECT AND
      METHODS: Auditory brainstem response (ABR) and the expression of SDF-1 mRNA and
      protein were examined 1, 3, 7, 14, and 30 days after application of ouabain in 35
      adult mice. RESULTS: Following ouabain application, real-time reverse
      transcription polymerase chain reaction for SDF demonstrates increased mRNA
      expression following ouabain injury in nontransplanted mice. A significant
      increase in SDF protein expression was also observed using immunolabeling
      techniques and Western blot analysis. CONCLUSIONS: SDF-1 expression is increased
      in the auditory nerve following cochlear injury. Further knowledge about the
      cochlear microenvironment, including SDF-1, is critical to maximizing HSC
      engraftment in the injured cochlea and providing a therapeutic option for
      sensorineural hearing loss.

PMID- 21947794
TI  - Linking zinc and leptin in chronic kidney disease: future directions.
AB  - Anorexia is a common complication in patients with chronic kidney disease (CKD)
      and is associated with the development of malnutrition and an increased risk of
      mortality. Several compounds are linked to anorexia in these patients; however,
      the mechanisms are unknown. Zinc (Zn) deficiency is associated with decreased
      food intake and has been observed in CKD patients. In addition, leptin is an
      anorexigenic peptide, and patients with CKD present generally high levels of this
      hormone. Studies have suggested an association between Zn and leptin status in
      human and rats; however, the results are inconsistent. Some claimed that Zn
      supplementation does not change leptin release or that there is no significant
      relationship between Zn and leptin. Others have reported that Zn might be a
      mediator of leptin production. CKD patients have hyperleptinemia and
      hypozincemia, but the relationship between Zn deficiency and leptin levels in CKD
      patients has been poorly understood until now. The aim of this review is to
      integrate knowledge on leptin and Zn actions to provide a cohesive clinical
      perspective regarding their interactions in CKD patients.

PMID- 21947795
TI  - Lead stress disrupts the cytoskeleton organization and cell wall construction
      during Picea wilsonii pollen germination and tube growth.
AB  - Lead is a widespread pollutant and has been reported to inhibit pollen tube
      development, but the mechanism of toxicity involved remains unclear. Here, we
      report that lead stress significantly prevented Picea wilsonii pollen germination
      and tube growth and also dramatically altered the tube morphology in a
      concentration-dependent manner. Fluorescence labeling with JIM 5 (anti-acidic
      pectin antibody) and Calcofluor white revealed the lead-induced decline of acidic
      pectin and cellulose, especially in the subapical region. Decolorized aniline
      blue staining showed the marked accumulation of callose in the apical and
      subapical regions of lead-treated tubes. Fluorescence labeling with Alexa Fluor
      568 phalloidin and anti-tubulin antibody revealed that the distribution of the
      cytoskeleton in P. wilsonii pollen grains and tubes were developmentally
      regulated and that lead disturbed the cytoskeleton organization, especially in
      the shank of the pollen tubes. Taken together, our experiments revealed a link
      between the dynamics of cytoskeleton organization and the process of P. wilsonii
      pollen tube development and also indicated that lead disturbed the cytoskeleton
      assembly and, consequently, cell wall construction. These findings provide new
      insights into the mechanism of lead toxicity in the tip growth of pollen tubes.

PMID- 21947796
TI  - Calibration of the mechanical properties in a finite element model of a lumbar
      vertebra under dynamic compression up to failure.
AB  - Finite element models (FEM) dedicated to vertebral fracture simulations rarely
      take into account the rate dependency of the bone material properties due to
      limited available data. This study aims to calibrate the mechanical properties of
      a vertebral body FEM using an inverse method based on experiments performed at
      slow and fast dynamic loading conditions. A detailed FEM of a human lumbar
      vertebral body (23,394 elements) was developed and tested under compression at
      2,500 and 10 mm s-1. A central composite design was used to adjust the mechanical
      properties (Young modulus, yield stress, and yield strain) while optimizing four
      criteria (ultimate strain and stress of cortical and trabecular bone) until the
      failure load and energy at failure reached experimental results from the
      literature. At 2,500 mm s-1, results from the calibrated simulation were in good
      agreement with the average experimental data (1.5% difference for the failure
      load and 0.1% for the energy). At 10 mm s-1, they were in good agreement with the
      average experimental failure load (0.6% difference), and within one standard
      deviation of the reported range of energy to failure. The proposed method
      provides a relevant mean to identify the mechanical properties of the vertebral
      body in dynamic loadings.

PMID- 21947797
TI  - A comparison of univariate, vector, bilinear autoregressive, and band power
      features for brain-computer interfaces.
AB  - Selecting suitable feature types is crucial to obtain good overall brain-computer
      interface performance. Popular feature types include logarithmic band power
      (logBP), autoregressive (AR) parameters, time-domain parameters, and wavelet
      based methods. In this study, we focused on different variants of AR models and
      compare performance with logBP features. In particular, we analyzed univariate,
      vector, and bilinear AR models. We used four-class motor imagery data from nine
      healthy users over two sessions. We used the first session to optimize parameters
      such as model order and frequency bands. We then evaluated optimized feature
      extraction methods on the unseen second session. We found that band power yields
      significantly higher classification accuracies than AR methods. However, we did
      not update the bias of the classifiers for the second session in our analysis
      procedure. When updating the bias at the beginning of a new session, we found no
      significant differences between all methods anymore. Furthermore, our results
      indicate that subject-specific optimization is not better than globally optimized
      parameters. The comparison within the AR methods showed that the vector model is
      significantly better than both univariate and bilinear variants. Finally, adding
      the prediction error variance to the feature space significantly improved
      classification results.

PMID- 21947798
TI  - Triggers and monitoring in intelligent personal health record.
AB  - Although Web-based personal health records (PHRs) have been widely deployed, the
      existing ones have limited intelligence. Previously, we introduced expert system
      technology and Web search technology into the PHR domain and proposed the concept
      of an intelligent PHR (iPHR). iPHR provides personalized healthcare information
      to facilitate users' daily activities of living. The current iPHR is passive and
      follows the pull model of information distribution. This paper introduces
      triggers and monitoring into iPHR to make iPHR become active. Our idea is to let
      medical professionals pre-compile triggers and store them in iPHR's knowledge
      base. Each trigger corresponds to an abnormal event that may have potential
      medical impact. iPHR keeps collecting, processing, and analyzing the user's
      medical data from various sources such as wearable sensors. Whenever an abnormal
      event is detected from the user's medical data, the corresponding trigger fires
      and the related personalized healthcare information is pushed to the user using
      natural language generation technology, expert system technology, and Web search
      technology.

PMID- 21947799
TI  - Acute phase response and oxidative stress status in familial Mediterranean fever
      (FMF).
AB  - We aimed to determine acute phase response (APR) and oxidative stress in patients
      with familial Mediterranean fever (FMF) and compare these characteristics with
      those in healthy controls; 20 patients with FMF and 15 healthy controls were
      enrolled in the study. The erythrocyte sedimentation rate (ESR), and C-reactive
      protein (CRP), fibrinogen, and leukocyte levels were determined as markers of
      APR. Thiobarbituric acid reactive substances (TBARS), conjugated diene, and lipid
      hydroperoxide levels were measured as markers of lipid peroxidation. Carbonyl
      group and thiol (T-SH) levels were analyzed to determine the oxidative damage to
      proteins, and 8-hydroxy-2-deoxyguanosine (8-OHdG) was measured to reflect DNA
      oxidation. The erythrocyte glutathione (GSH) level, and glutathione peroxidase
      (GSH-Px), CuZn superoxide dismutase (CuZn SOD), and catalase activities were
      measured as markers of antioxidant status. Conjugated diene (p < 0.001) and
      carbonyl group (p < 0.05) levels were significantly higher and GSH-Px activity (p
      < 0.01) was significantly lower in FMF patients compared with controls. FMF
      patients in the attack period (n = 8) had significantly higher CRP, ESR,
      fibrinogen, and leukocyte levels (p < 0.001) than patients in the attack-free
      period (n = 12). The T-SH level (p < 0.05) was significantly higher and CuZn SOD
      activity was significantly lower (p < 0.05) in FMF patients in the attack period.
      The findings revealed upregulated APR during the attack period in FMF patients
      and enhanced oxidative stress in the FMF patients as compared to controls.

PMID- 21947800
TI  - The role of the principle of double effect in ethics education at US medical
      schools and its potential impact on pain management at the end of life.
AB  - BACKGROUND: Because opioids can suppress respiratory drive, the principle of
      double effect (PDE) has been used to justify their use for terminally ill
      patients. Recent studies, however, suggest that the risk of respiratory
      depression in typical end-of-life (EOL) situations may be overstated and that
      heightened concern for this rare occurrence can lead to inadequate treatment of
      pain. The purpose of this study is to examine the role of the PDE in medical
      school ethics education, with specific reference to its potential impact on pain
      management at EOL. METHOD: After obtaining institutional review board approval,
      an electronic survey was sent to ethics educators at every allopathic medical
      school in the USA. RESULTS: One-third of ethics educators felt that opioids were
      'likely' to cause significant respiratory depression that could hasten death.
      Educators' opinions of opioid effects did not influence their view of the
      relevance of the PDE, with approximately 70% deeming it relevant to EOL care.
      Only 15% of ethics educators believed that associating the PDE with opioid use
      might discourage clinicians from optimally treating pain, out of concern for
      respiratory depression. CONCLUSION: This study demonstrates that a significant
      minority of ethics educators believe, contrary to current evidence, that opioids
      are 'likely' to cause significant respiratory depression that could hasten death
      in terminally ill patients. Yet, many of those who do not feel this is likely
      still rely on the PDE to justify this possibility, potentially (and unknowingly)
      contributing to clinical misperceptions and underutilisation of opioids at EOL.

PMID- 21947801
TI  - Working together. An interdisciplinary approach to dying patients in a palliative
      care unit.
AB  - Multiprofessional teams have become in recent years one of the distinguishing
      features of services, where professionals with different competences work
      together. The core of our interest is addressed to the equipe of a palliative
      care ward; in particular, to that series of working activities that consists of
      communicative acts, as equipe meetings, for instance. Our research focuses on the
      analysis of the process by which the development of knowledge in
      multiprofessional practice is built to establish more information on recurrent
      patterns in the interaction and connect them to the specific context that these
      are shaped by. In this sense we will underline how components of knowing are
      shared among team members in constructing medical prognosis and we will analyse
      the connection among language processes, cognitive activities and social
      structures. More specifically, we will study the role of language and the context
      in the definition of linguistic acts in cognitive activities and in hierarchies
      involved in decision-making processes by exploring and pointing out how it is
      organised and structured. In particular through the study of talk-in-interaction
      where interchange of information is realised, we will emphasise how, in the
      multiprofessional equipe meeting, the realisation of practices and the knowledge
      useful to collaborative management of ward working life are established. To reach
      this aim, we adopted an ethnographic approach connected to the analysis of the
      situated interaction.

PMID- 21947802
TI  - Ethical practice in internet research involving vulnerable people: lessons from a
      self-harm discussion forum study (SharpTalk).
AB  - The internet is widely used for health information and support, often by
      vulnerable people. Internet-based research raises both familiar and new ethical
      problems for researchers and ethics committees. While guidelines for internet
      based research are available, it is unclear to what extent ethics committees use
      these. Experience of gaining research ethics approval for a UK study (SharpTalk),
      involving internet-based discussion groups with young people who self-harm and
      health professionals is described. During ethical review, unsurprisingly,
      concerns were raised about the vulnerability of potential participants. These
      were dominated by the issue of anonymity, which also affected participant safety
      and consent. These ethical problems are discussed, and our solutions, which
      included: participant usernames specific to the study, a closed website, private
      messaging facilities, a direct contact email to researchers, information about
      forum rules displayed on the website, a 'report' button for participants, links
      to online support, and a discussion room for forum moderators. This experience
      with SharpTalk suggests that an approach to ethics, which recognises the
      relational aspects of research with vulnerable people, is particularly useful for
      internet-based health research. The solutions presented here can act as guidance
      for researchers developing proposals and for ethics committees reviewing them.

PMID- 21947803
TI  - Neurotrauma and the rule of rescue.
AB  - The rule of rescue describes the powerful human proclivity to rescue identified
      endangered lives, regardless of cost or risk. Deciding whether or not to perform
      a decompressive craniectomy as a life-saving or 'rescue' procedure for a young
      person with a severe traumatic brain injury provides a good example of the
      ethical tensions that occur in these situations. Unfortunately, there comes a
      point when the primary brain injury is so severe that if the patient survives
      they are likely to remain severely disabled and fully dependent. The health
      resource implications of this outcome are significant. By using a web-based
      outcome prediction model this study compares the long-term outcome and
      designation of two groups of patients. One group had a very severe injury as
      adjudged by the model and the other group a less severe injury. At 18 month
      follow-up there were significant differences in outcome and healthcare
      requirements. This raises important ethical issues when considering life-saving
      but non-restorative surgical intervention. The discussion about realistic outcome
      cannot be dichotomised into simply life or death so that the outcome for the
      patient must enter the equation. As in other 'rescue situations', the utility of
      the procedure cannot be rationalised on a mere cost-benefit analysis. A
      compromise has to be reached to determine at what point either the likely outcome
      would be unacceptable to the person on whom the procedure is being performed or
      the social utility gained from the rule of rescue intervention fails to justify
      the utilitarian value and justice of equitable resource allocation.

PMID- 21947805
TI  - A fair share for the orphans: ethical guidelines for a fair distribution of
      resources within the bounds of the 10-year-old European Orphan Drug Regulation.
AB  - For a significant number of patients, there exists no, or only little, interest
      in developing a treatment for their disease or condition. Especially with regard
      to rare diseases, the lack of commercial interest in drug development is a
      burning issue. Several interventions have been made in the regulatory field in
      order to address the commercial disinterest in these conditions. However,
      existing regulations mainly focus on the provision of incentives to the sponsors
      of clinical trials of orphan drugs, and leave unanswered the overarching question
      about the rightful place of orphan drugs in resource allocation systems. In this
      article, we analyse the ethical aspects of funding research and development in
      the field of rare diseases. We then propose an ethical framework that can help
      health policy makers move forward in the difficult matter of fairly allocating
      resources for the prevention, diagnosis and treatment of rare diseases.

PMID- 21947804
TI  - Is medical students' moral orientation changeable after preclinical medical
      education?
AB  - PURPOSE: Moral orientation can affect ethical decision-making. Very few studies
      have focused on whether medical education can change the moral orientation of the
      students. The purpose of the present study was to document the types of moral
      orientation exhibited by medical students, and to study if their moral
      orientation was changed after preclinical education. METHODS: From 2007 to 2009,
      the Mojac scale was used to measure the moral orientation of Taiwan medical
      students. The students included 271 first-year and 109 third-year students. They
      were rated as a communitarian, dual, or libertarian group and followed for 2
      years to monitor the changes in their Mojac scores. RESULTS: In both first and
      third-year students, the dual group after 2 years of preclinical medical
      education did not show any significant change. In the libertarian group, first
      and third-year students showed a statistically significant increase from a score
      of 99.4 and 101.3 to 103.0 and 105.7, respectively. In the communitarian group,
      first and third-year students showed a significant decline from 122.8 and 126.1
      to 116.0 and 121.5, respectively. CONCLUSION: During the preclinical medical
      education years, students with communitarian orientation and libertarian
      orientation had changed in their moral orientation to become closer to dual
      orientation. These findings provide valuable hints to medical educators regarding
      bioethics education and the selection criteria of medical students for admission.

PMID- 21947806
TI  - Provider, patient and public benefits from a NICE appraisal of bevacizumab
      (Avastin).
AB  - There are several good reasons for the UK Department of Health to recommend the
      appraisal of bevacizumab for the treatment of eye conditions by the National
      Institute for Health and Clinical Excellence. These reasons will extend to other
      drugs when similar situations arise in the future.

PMID- 21947807
TI  - 'Unbearable suffering': a qualitative study on the perspectives of patients who
      request assistance in dying.
AB  - BACKGROUND: One of the objectives of medicine is to relieve patients' suffering.
      As a consequence, it is important to understand patients' perspectives of
      suffering and their ability to cope. However, there is poor insight into what
      determines their suffering and their ability to bear it. PURPOSE: To explore the
      constituent elements of suffering of patients who explicitly request euthanasia
      or physician-assisted suicide (EAS) and to better understand unbearable suffering
      from the patients' perspective. PATIENTS AND METHODS: A qualitative study using
      in-depth face-to-face interviews was conducted with 31 patients who had requested
      EAS. The grounded theory approach was used to analyse the data. RESULTS: Medical,
      psycho-emotional, socio-environmental and existential themes contributed to
      suffering. Especially fatigue, pain, decline, negative feelings, loss of self,
      fear of future suffering, dependency, loss of autonomy, being worn out, being a
      burden, loneliness, loss of all that makes life worth living, hopelessness,
      pointlessness and being tired of living were constituent elements of unbearable
      suffering. Only patients with a psychiatric (co)diagnosis suffered unbearably all
      the time. CONCLUSIONS: Unbearable suffering is the outcome of an intensive
      process that originates in the symptoms of illness and/or ageing. According to
      patients, hopelessness is an essential element of unbearable suffering. Medical
      and social elements may cause suffering, but especially when accompanied by
      psycho-emotional and existential problems suffering will become 'unbearable'.
      Personality characteristics and biographical aspects greatly influence the burden
      of suffering. Unbearable suffering can only be understood in the continuum of the
      patients' perspectives of the past, the present and expectations of the future.

PMID- 21947808
TI  - Sharing the benefits of research fairly: two approaches.
AB  - Research projects sponsored by rich countries or companies and carried out in
      developing countries are often described as exploitative. One important debate
      about the prevention of exploitation in research centres on whether and how
      clinical research in developing countries should be responsive to local health
      problems. This paper analyses the responsiveness debate and draws out more
      general lessons for how policy makers can prevent exploitation in various
      research contexts. There are two independent ways to do this in the face of
      entrenched power differences: to impose restrictions on the content of benefit
      sharing arrangements, and to institute independent effective oversight. Which
      method should be chosen is highly dependent on context.

PMID- 21947809
TI  - A fair trial? Assessment of liver transplant candidates with psychiatric
      illnesses.
AB  - Allocating scarce organs to transplant candidates is only one stage in the long
      process of organ transplantation. Before being listed, all candidates must
      undergo a rigorous assessment by a multidisciplinary transplant team. The
      Department of Health and NHS Blood and Transplant (NHSBT) are responsible for the
      development of detailed strategies to ensure a fair and objective assessment
      experience for all transplant candidates. Difficulties arise when particularly
      vulnerable candidates, such as candidates with psychiatric illnesses, are
      assessed. NHSBT has already developed unique assessment guidelines for alcoholic
      and substance-abusing liver transplant candidates to allow for a more
      comprehensive evaluation, but candidates with psychiatric illnesses are still
      assessed against general criteria. Should these candidates be assessed against
      their own criteria? On what clinical grounds do transplant teams justify
      excluding such candidates from transplantation? Is redress available for
      candidates who feel they have been unfairly refused a liver transplant simply
      because of their psychiatric illness? This essay will critically examine the
      provisions published by the Department of Health and NHSBT for the assessment of
      liver transplant candidates with psychiatric illnesses, and will provide a
      commentary as to whether enough is being done to protect these particularly
      vulnerable candidates from inconsistent assessment decisions.

PMID- 21947810
TI  - The case of biobank with the law: between a legal and scientific fiction.
AB  - According to estimates more than 400 biobanks currently operate across Europe.
      The term 'biobank' indicates a specific field of genetic study that has quietly
      developed without any significant critical reflection across European societies.
      Although scientists now routinely use this phrase, the wider public is still
      confused when the word 'bank' is being connected with the collection of their
      biological samples. There is a striking lack of knowledge of this field. In the
      recent Eurobarometer survey it was demonstrated that even in 2010 two-thirds of
      the respondents had never even heard about biobanks. The term gives the
      impression that a systematic collection of biological samples can constitute a
      'bank' of considerable financial worth, where the biological samples, which are
      insignificant in isolation but are valuable as a collection, can be preserved,
      analysed and put to 'profitable use'. By studying the practices of the numerous
      already existing biobanks, the authors address the following questions: to what
      extent does the term 'biobank' reflect the normative concept of using biological
      samples for the purposes of biomedical research? Furthermore, is it in harmony
      with the so far agreed legal-ethical consensus in Europe or does it deliberately
      pull science to the territory of a new, ambiguous commercial field? In other
      words, do biobanks constitute a medico-legal fiction or are they substantively
      different from other biomedical research protocols on human tissues?

PMID- 21947811
TI  - Through students' eyes: ethical and professional issues identified by third-year
      medical students during clerkships.
AB  - BACKGROUND: Education in ethics and professionalism should reflect the realities
      medical students encounter in the hospital and clinic. METHOD: We performed
      content analyses on Case Observation and Assessments (COAs) written by third-year
      medical students about ethical and professional issues encountered during their
      internal medicine and paediatrics clinical clerkships. RESULTS: A cohort of 141
      third-year medical students wrote 272 COAs. Content analyses identified 35
      subcategories of ethical and professional issues within 7 major domains:
      decisions regarding treatment (31.4%), communication (21.4%), professional duties
      (18.4%), justice (9.8%), student-specific issues (5.4%), quality of care (3.8%),
      and miscellaneous (9.8%). CONCLUSIONS: Students encountered a wide variety of
      ethical and professional issues that can be used to guide pre-clinical and
      clinical education. Comparison of our findings with results from similar studies
      suggests that the wording of an assignment (specifying "ethical" issues,
      "professional" issues, or both) may influence the kinds of issues students
      identify in their experience-based clinical narratives.

PMID- 21947812
TI  - Sparrow's song revisited.

PMID- 21947814
TI  - Care of the multisport athlete: lessons from Goldilocks.

PMID- 21947813
TI  - The effect of different doses of aerobic exercise training on endothelial
      function in postmenopausal women with elevated blood pressure: results from the
      DREW study.
AB  - OBJECTIVES: The aim of this study was to examine the effect of three different
      doses of aerobic exercise training (corresponding to approximately 50%, 100% and
      150% of the National Institutes of Health consensus guidelines) on endothelial
      function in sedentary obese postmenopausal women with elevated blood pressure.
      Aerobic exercise training improves endothelial function in individuals with
      cardiovascular risk; however, it is unknown whether these adaptations occur in a
      dose-dependent manner. METHODS: Obese postmenopausal women (n=155) with elevated
      blood pressure (systolic blood pressure between 120 and 159.0 mm Hg) were
      randomly assigned to one of four groups: 4, 8 or 12 kilocalories per kilogram of
      energy expenditure per week (kcal/kg/week) or a non-exercise control group for 6
      months. Endothelial function was assessed via flow-mediated dilation (FMD) at
      baseline and post-intervention. RESULTS: After exercise training, there was a
      similar improvement (1.02-1.5%) in FMD in all three exercise groups (p<0.05)
      compared with control (-0.5%). Change in FMD after exercise training was
      significantly correlated with FMD at baseline (r= -0.35, p<0.001). Post hoc
      analyses found a significant improvement in FMD in exercisers (all exercise
      groups combined) with endothelial dysfunction (FMD < 5.5%) at baseline (1.8%, 95%
      CI: 1.17 to 2.38; p<0.001) compared with exercisers with normal endothelial
      function (FMD >= 5.5%) (-1.2%; 95% CI: -1.17 to 0.69; p=0.60). CONCLUSIONS:
      Aerobic exercise training was associated with improved FMD in postmenopausal
      women with elevated blood pressure. In addition, exercise training may be more
      efficacious in improving endothelial function in postmenopausal women with
      endothelial dysfunction than individuals with normal endothelial function at
      baseline.

PMID- 21947815
TI  - Injury surveillance during the 2010 IRB Women's Rugby World Cup.
AB  - OBJECTIVE: To assess and evaluate injuries sustained during the 2010 Women's
      Rugby World Cup. DESIGN: Prospective, cohort. PARTICIPANTS: 285 women rugby
      players. RESULTS: Incidence of match injury was 35.5/1000 player-hours; mean
      severity was 55.0 days and median severity 9 days. Only one training injury was
      reported. Knee-ligament injuries were the most common (15%) and resulted in most
      days lost (43%). The tackle was the cause of most injuries. CONCLUSIONS: The risk
      of injury in international rugby is significantly lower for women than for men.
      Further research is required to assess knee-ligament injuries in women's rugby.

PMID- 21947816
TI  - Cold water immersion and recovery from strenuous exercise: a meta-analysis.

PMID- 21947817
TI  - A tool for measuring workers' sitting time by domain: the Workforce Sitting
      Questionnaire.
AB  - BACKGROUND: Sitting time is an emerging health risk, and many working adults
      spend large amounts of time sitting each day. It is important to have reliable
      and accurate measurement tools to assess sitting time in different contexts.
      OBJECTIVE: To validate the Workforce Sitting Questionnaire (WSQ), an adapted
      measure of total and domain-specific sitting time based on work and non-workdays
      for use in working adults. METHODS: A convenience sample (N=95, 63.2% women) was
      recruited from two workplaces and by word-of-mouth in Sydney, Australia.
      Participants completed the WSQ, which asked about sitting time (1) while
      travelling to and from places; (2) while at work; (3) while watching TV; (4)
      while using a computer at home; and (5) while doing other leisure activities on
      work and non-workdays on two occasions, 7 days apart. Participants also wore an
      accelerometer for the 7 days between test and retest. They recorded the times
      they wore the accelerometer, the days they worked and their work times in a
      logbook. Analyses determined test-retest reliability with intraclass correlation
      coefficients (ICCs) and assessed criterion validity against accelerometers using
      Spearman's r and Bland-Altman plots. RESULTS: Measuring total sitting time based
      on a workday, non-workday and on average had fair to excellent test-retest
      reliability (ICC=0.46-0.90) and had sufficient criterion validity against
      accelerometry in women (r=0.22-0.46) and men (r=0.18-0.29). Measuring domain
      specific sitting at work on a workday was also reliable (ICC=0.63) and valid
      (r=0.45). CONCLUSIONS: The WSQ has acceptable measurement properties for
      measuring sitting time at work on a workday and for assessing total sitting time
      based on work and non-workdays. This questionnaire would be suitable for use in
      research investigating the relationships between sitting time and health in
      working populations.

PMID- 21947818
TI  - Oxidized LDL, LOX-1 and atherosclerosis.
AB  - An elevated level of low density lipoprotein (LDL) cholesterol constitutes a
      major risk factor for genesis of atherosclerosis. Ox-LDL plays a more important
      role in the genesis and progression of atherosclerosis than the native LDL. Ox
      LDL leads to endothelial dysfunction leading to expression of adhesion molecules
      and recruitment of monocyte in subendothelial space. Ox-LDL is taken up by
      macrophages via scavenger receptors, such as SR-A1, SR-A2 and LOX-1. Lately, LOX
      1, a type II membrane protein receptor of ox-LDL, has gained much importance in
      relation to effects of ox-LDL on endothelial biology. Endothelial cells primarily
      express LOX-1 as receptor for ox-LDL and ox-LDL has been shown to upregulate
      expression of LOX-1. In addition, ox-LDL promotes the growth and migration of
      smooth muscle cells, monocytes/macrophages and fibroblasts. In this review we
      discuss the role of ox-LDL and LOX-1 in genesis and progression of
      atherosclerosis.

PMID- 21947819
TI  - Centralization in patients with sciatica: are pain responses to repeated movement
      and positioning associated with outcome or types of disc lesions?
AB  - AIM: To determine the frequency of different patterns of centralization and their
      association with outcomes and MRI findings in patients experiencing sciatica.
      METHODS: A prospective longitudinal cohort study of 176 patients with radicular
      pain below the knee, who all had an MDT clinical assessment. Based on their pain
      response, patients were divided into five groups: abolition centralization,
      reduction centralization, unstable centralization, peripheralization, and "no
      effect". Patients had an MRI. RESULTS: Overall, 84.8% of patients reported
      experiencing centralization, 7.3% peripheralized and 7.9% reported "no effect".
      The median reduction in RMQ scores across all the three centralization groups was
      9.5 points at 3 months, and 12.0 points at 12 months. The peripheralization group
      improved similarly. The 'no effect' group improved significantly lower (p <
      0.001), by 3.0 at both time points. Patients who centralized, and peripheralized
      had a significantly reduction in leg pain, the "no effect" group demonstrated a
      less favorable outcome (p < 0.02). There was no association between pain
      responses and the type of disc lesion. CONCLUSION: In patients with sciatica,
      centralization was common and associated with improvement in activity limitation
      and leg pain. Centralization was very common in ruptured disc therefore the study
      does not support the theory, that centralization only occurs if the intra-discal
      hydrostatic mechanism is functional.

PMID- 21947820
TI  - Effects of knee immobilization on morphological changes in the semitendinosus
      muscle-tendon complex after hamstring harvesting for anterior cruciate ligament
      reconstruction: evaluation using three-dimensional computed tomography.
AB  - BACKGROUND: It is desirable to maintain the morphology of the semitendinosus
      muscle-tendon complex after tendon harvesting for anterior cruciate ligament
      (ACL) reconstruction. The purpose of this study was to evaluate the effect of
      knee immobilization on morphological changes in the semitendinosus muscle-tendon
      complex. METHODS: In total, 39 patients who underwent ACL reconstruction with
      autologous semitendinosus tendons were included in this study. After surgery, the
      knee was immobilized for 3 days in 1 group of patients (group 1; 24 patients;
      control group) and for a longer period (10-14 days) in the other group (group 2;
      15 patients). Three-dimensional computed tomography (3D CT) examination was
      performed at 6 and/or 12 months after the surgery for all patients. Morphological
      changes in the semitendinosus muscle-tendon complex (proximal shift of the
      semitendinosus muscle-tendon junction, width of the regenerated semitendinosus
      tendons, re-insertion sites of the regenerated tendons, and rate of
      semitendinosus tendon regeneration) were evaluated. RESULTS: Successful
      regeneration of the semitendinosus tendon was confirmed in all patients in group
      2. In group 1, 3D CT showed that regeneration of the semitendinosus tendon was
      unsuccessful in 1 of the 24 patients. The average length of the proximal shift of
      the semitendinosus muscle-tendon junction was 7.3 +/- 2.5 cm in group 1 and 7.2
      +/- 1.9 cm in group 2. There were no significant differences between the 2 groups
      with regard to the morphological changes in the semitendinosus muscle-tendon
      complex. CONCLUSIONS: This study showed that the structure of regenerated tendons
      could be clearly identified in 38 of 39 cases (97.4%) after ACL reconstruction.
      However, prolonged knee immobilization (10-14 days) could not prevent
      morphological changes in the semitendinosus muscle-tendon complex.

PMID- 21947821
TI  - Determining true HER2 gene status in breast cancers with polysomy by using
      alternative chromosome 17 reference genes: implications for anti-HER2 targeted
      therapy.
AB  - PURPOSE: The ratio of human epidermal growth factor receptor 2 (HER2) to CEP17 by
      fluorescent in situ hybridization (FISH) with the centromeric probe CEP17 is used
      to determine HER2 gene status in breast cancer. Increases in CEP17 copy number
      have been interpreted as representing polysomy 17. However, pangenomic studies
      have demonstrated that polysomy 17 is rare. This study tests the hypothesis that
      the use of alternative chromosome 17 reference genes might more accurately assess
      true HER2 gene status. PATIENTS AND METHODS: In all, 171 patients with breast
      cancer who had HER2 FISH that had increased mean CEP17 copy numbers (> 2.6) were
      selected for additional chromosome 17 studies that used probes for Smith-Magenis
      syndrome (SMS), retinoic acid receptor alpha (RARA), and tumor protein p53 (TP53)
      genes. A eusomic copy number exhibited in one or more of these loci was used to
      calculate a revised HER2-to-chromosome-17 ratio by using the eusomic gene locus
      as the reference. RESULTS: Of 132 cases classified as nonamplified on the basis
      of their HER2:CEP17 ratios, 58 (43.9%) were scored as amplified by using
      alternative chromosome 17 reference gene probes, and 13 (92.9%) of 14 cases
      scored as equivocal were reclassified as amplified. Among the cases with mean
      HER2 copy number of 4 to 6, 41 (47.7%) of 86 had their HER2 gene status upgraded
      from nonamplified to amplified, and four (4.7%) of 86 were upgraded from
      equivocal to amplified. CONCLUSION: Our results support the findings of recent
      pangenomic studies that true polysomy 17 is uncommon. Additional FISH studies
      that use probes to the SMS, RARA, and TP53 genes are an effective way to
      determine the true HER2 amplification status in patients with polysomy 17 and
      they have important potential implications for guiding HER2-targeted therapy in
      breast cancer.

PMID- 21947822
TI  - Clinical impact of pathology reviews of outside material: a patient-focused
      approach.

PMID- 21947823
TI  - Misunderstanding regarding the carboplatin dose comparison in MRC TE19/EORTC
      30982.

PMID- 21947824
TI  - The germinal center/activated B-cell subclassification has a prognostic impact
      for response to salvage therapy in relapsed/refractory diffuse large B-cell
      lymphoma: a bio-CORAL study.
AB  - PURPOSE: To evaluate the prognostic value of the cell of origin (COO) in patients
      with relapsed/refractory diffuse large B-cell lymphoma (DLBLC), prospectively
      treated by rituximab, dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP)
      versus rituximab, ifosfamide, carboplatin, and etoposide and followed by
      intensive therapy plus autologous stem-cell transplantation on the Collaborative
      Trial in Relapsed Aggressive Lymphoma (CORAL) trial. PATIENTS AND METHODS: Among
      the 396 patients included on the trial, histologic material was available for a
      total of 249 patients at diagnosis (n = 189 patients) and/or at relapse (n = 147
      patients), which included 87 matched pairs. The patient data were analyzed by
      immunochemistry for CD10, BCL6, MUM1, FOXP1, and BCL2 expression and by
      fluorescent in situ hybridization for BCL2, BCL6 and c-MYC breakpoints. The
      correlation with survival data was performed by using the log-rank test and the
      Cox model. RESULTS: Characteristics of immunophenotype and chromosomal
      abnormalities were statistically highly concordant in the matched biopsies. In
      univariate analysis, the presence of c-MYC gene rearrangement was the only
      parameter to be significantly correlated with a worse progression-free survival
      (PFS; P = .02) and a worse overall survival (P = .04). When treatment interaction
      was tested, the germinal center B (GCB) -like DLBCL that was based on the
      algorithm by Hans was significantly associated with a better PFS in the R-DHAP
      arm. In multivariate analysis, independent prognostic relevance was found for the
      GCB/non-GCB the Hans phenotype interaction treatment (P = .04), prior rituximab
      exposure (P = .0052), secondary age-adjusted International Prognostic Index (P =
      .039), and FoxP1 expression (P = .047). Confirmation was obtained by gene
      expression profiling in a subset of 39 patients. CONCLUSION: COO remains a major
      and independent factor in relapsed/refractory DLBCL, with a better response to R
      DHAP in GCB-like DLBCL. This needs confirmation by a prospective study.

PMID- 21947825
TI  - DNA repair capacity in peripheral lymphocytes predicts survival of patients with
      non-small-cell lung cancer treated with first-line platinum-based chemotherapy.
AB  - PURPOSE: Platinum-based regimens are the standard chemotherapy for patients with
      advanced non-small-cell lung cancer (NSCLC). DNA repair capacity (DRC) in tumor
      cells plays an important role in resistance to platinum-based drugs. We have
      previously reported that efficient DRC, as assessed by an in vitro lymphocyte
      based assay, was a determinant of poor survival in patients with NSCLC in a
      relatively small data set. In this larger independent study of 591 patients with
      NSCLC, we further evaluated whether DRC in peripheral lymphocytes predicts
      survival of patients with NSCLC who receive platinum-based chemotherapy. PATIENTS
      AND METHODS: All patients were recruited at The University of Texas MD Anderson
      Cancer Center and donated blood samples before the start of any chemotherapy. We
      measured DRC in cultured T lymphocytes by using the host-cell reactivation assay,
      and we assessed associations between DRC in peripheral lymphocytes and survival
      of patients with NSCLC who were treated with first-line platinum-based
      chemotherapy. RESULTS: We found an inverse association between DRC in peripheral
      lymphocytes and patient survival. Compared with patients in the low tertile of
      DRC, patients with NSCLC in the high tertile of DRC had significantly worse
      overall and 3-year survival (adjusted hazard ratio [HR], 1.33; 95% CI, 1.04 to
      1.71; P = .023; and HR, 1.35; 95% CI, 1.04 to 1.76; P = .025, respectively). This
      trend was more pronounced in patients with early-stage tumors, adenocarcinoma, or
      squamous cell carcinoma. CONCLUSION: We confirmed that DRC in peripheral
      lymphocytes is an independent predictor of survival for patients with NSCLC
      treated with platinum-based chemotherapy.

PMID- 21947826
TI  - Are large sample size studies the answer to evaluate effects of drug use in non
      clinical trial settings?

PMID- 21947827
TI  - Carboplatin in clinical stage I seminoma: a valuable option for patient
      management.

PMID- 21947828
TI  - Estrogen receptor (ESR1) mRNA expression and benefit from tamoxifen in the
      treatment and prevention of estrogen receptor-positive breast cancer.
AB  - PURPOSE: Several mechanisms have been proposed to explain tamoxifen resistance of
      estrogen receptor (ER) -positive tumors, but a clinically useful explanation for
      such resistance has not been described. Because the ER is the treatment target
      for tamoxifen, a linear association between ER expression levels and the degree
      of benefit from tamoxifen might be expected. However, such an association has
      never been demonstrated with conventional clinical ER assays, and the ER is
      currently used clinically as a dichotomous marker. We used gene expression
      profiling and ER protein assays to help elucidate molecular mechanism(s)
      responsible for tamoxifen resistance in breast tumors. PATIENTS AND METHODS: We
      performed gene expression profiling of paraffin-embedded tumors from National
      Surgical Adjuvant Breast and Bowel Project (NSABP) trials that tested the worth
      of tamoxifen as an adjuvant systemic therapy (B-14) and as a preventive agent (P
      1). This was a retrospective subset analysis based on available materials.
      RESULTS: In B-14, ESR1 was the strongest linear predictor of tamoxifen benefit
      among 16 genes examined, including PGR and ERBB2. On the basis of these data, we
      hypothesized that, in the P-1 trial, a lower level of ESR1 mRNA in the tamoxifen
      arm was the main difference between the two study arms. Only ESR1 was
      downregulated by more than two-fold in ER-positive cancer events in the tamoxifen
      arm (P < .001). Tamoxifen did not prevent ER-positive tumors with low levels of
      ESR1 expression. CONCLUSION: These data suggest that low-level expression of ESR1
      is a determinant of tamoxifen resistance in ER-positive breast cancer. Strategies
      should be developed to identify, treat, and prevent such tumors.

PMID- 21947829
TI  - Prospective study on incidence, risk factors, and long-term outcome of
      osteonecrosis in pediatric acute lymphoblastic leukemia.
AB  - PURPOSE: We studied cumulative incidence, risk factors, therapeutic strategies,
      and outcome of symptomatic osteonecrosis in pediatric patients with acute
      lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Cumulative incidence of
      osteonecrosis was assessed prospectively in 694 patients treated with the
      dexamethasone-based Dutch Child Oncology Group-ALL9 protocol. Osteonecrosis was
      defined by development of symptoms (National Cancer Institute grade 2 to 4)
      during treatment or within 1 year after treatment discontinuation, confirmed by
      magnetic resonance imaging. We evaluated risk factors for osteonecrosis using
      logistic multivariate regression. To describe outcome, we reviewed clinical and
      radiologic information after antileukemic treatment 1 year or more after
      osteonecrosis diagnosis. RESULTS: Cumulative incidence of osteonecrosis at 3
      years was 6.1%. After adjustment for treatment center, logistic multivariate
      regression identified age (odds ratio [OR], 1.47; P < .01) and female sex (OR,
      2.23; P = .04) as independent risk factors. Median age at diagnosis of ALL in
      patients with osteonecrosis was 13.5 years, compared with 4.7 years in those
      without. In 21 (55%) of 38 patients with osteonecrosis, chemotherapy was
      adjusted. Seven patients (18%) underwent surgery: five joint-preserving
      procedures and two total-hip arthroplasties. Clinical follow-up of 35 patients
      was evaluated; median follow-up was 4.9 years. In 14 patients (40%), symptoms
      completely resolved; 14 (40%) had symptoms interfering with function but not with
      activities of daily living (ADLs; grade 2); seven (20%) had symptoms interfering
      with ADLs (grade 3). In 24 patients, radiologic follow-up was available; in six
      (25%), lesions improved/disappeared; in 13 (54%), lesions remained stable; five
      (21%) had progressive lesions. CONCLUSION: Six percent of pediatric patients with
      ALL developed symptomatic osteonecrosis during or shortly after treatment. Older
      age and female sex were risk factors. After a median follow-up of 5 years, 60% of
      patients had persistent symptoms.

PMID- 21947830
TI  - Synchronous tumor with diffuse large B-cell lymphoma and ameboma.

PMID- 21947831
TI  - Relapsed diffuse large B-cell lymphoma: clinical utility of cell of origin.

PMID- 21947832
TI  - Cancer, diabetes, and angiotensin blockade: a question of hypohydration.

PMID- 21947833
TI  - Health care use of long-term survivors of childhood cancer: the British Childhood
      Cancer Survivor Study.
AB  - PURPOSE: Survivors of childhood cancer are at high risk of chronic conditions,
      but few studies investigated whether this translates into increased health care
      utilization. We compared health care service utilization between childhood cancer
      survivors and the general British population and investigated potential risk
      factors. METHODS: We used data from the British Childhood Cancer Survivor Study,
      a population-based cohort of 17,981 individuals diagnosed with childhood cancer
      (1940-1991) and surviving >= 5 years. Frequency of talks to a doctor, hospital
      outpatient visits, and day-patient and inpatient hospitalizations were
      ascertained by questionnaire in 10,483 survivors and were compared with the
      General Household Survey 2002 data by using logistic regression. RESULTS: Among
      survivors, 16.5% had talked to a doctor in the last 2 weeks, 25.5% had attended
      the outpatient department of a hospital in the last 3 months, 11.9% had been
      hospitalized as a day patient in the last 12 months, and 9.8% had been
      hospitalized as an inpatient in the last 12 months. Survivors had talked slightly
      more often to a doctor than the general population (odds ratio [OR], 1.2; 95% CI,
      1.1 to 1.3) and experienced increased hospital outpatient visits (OR, 2.5; 95%
      CI, 2.3 to 2.8), day-patient hospitalizations (OR, 1.4; 95% CI, 1.3 to 1.6) and
      inpatient hospitalizations (OR, 1.9; 95% CI, 1.7 to 2.2). Survivors of Hodgkin's
      lymphoma, neuroblastoma, and Wilms tumor had the highest ORs for day-patient
      care, whereas survivors of CNS tumors and bone sarcomas had the highest OR for
      outpatient and inpatient care. The OR of health care use did not vary
      significantly with age of survivor. CONCLUSION: We have quantified how excess
      morbidity experienced by survivors of childhood cancer translates into increased
      use of health care facilities.

PMID- 21947834
TI  - Antiemetics: American Society of Clinical Oncology clinical practice guideline
      update.
AB  - PURPOSE: To update the American Society of Clinical Oncology (ASCO) guideline for
      antiemetics in oncology. METHODS: A systematic review of the medical literature
      was completed to inform this update. MEDLINE, the Cochrane Collaboration Library,
      and meeting materials from ASCO and the Multinational Association for Supportive
      Care in Cancer were all searched. Primary outcomes of interest were complete
      response and rates of any vomiting or nausea. RESULTS: Thirty-seven trials met
      prespecified inclusion and exclusion criteria for this systematic review. Two
      systematic reviews from the Cochrane Collaboration were identified; one surveyed
      the pediatric literature. The other compared the relative efficacy of the 5
      hydroxytryptamine-3 (5-HT(3)) receptor antagonists. RECOMMENDATIONS: Combined
      anthracycline and cyclophosphamide regimens were reclassified as highly emetic.
      Patients who receive this combination or any highly emetic agents should receive
      a 5-HT(3) receptor antagonist, dexamethasone, and a neurokinin 1 (NK(1)) receptor
      antagonist. A large trial validated the equivalency of fosaprepitant, a single
      day intravenous formulation, with aprepitant; either therapy is appropriate.
      Preferential use of palonosetron is recommended for moderate emetic risk
      regimens, combined with dexamethasone. For low-risk agents, patients can be
      offered dexamethasone before the first dose of chemotherapy. Patients undergoing
      high emetic risk radiation therapy should receive a 5-HT(3) receptor antagonist
      before each fraction and for 24 hours after treatment and may receive a 5-day
      course of dexamethasone during fractions 1 to 5. The Update Committee noted the
      importance of continued symptom monitoring throughout therapy. Clinicians
      underestimate the incidence of nausea, which is not as well controlled as emesis.

PMID- 21947835
TI  - How treatment partners help: social analysis of an African adherence support
      intervention.
AB  - Treatment partnering is an adherence intervention developed in sub-Saharan
      Africa. This paper describes the additional social functions that treatment
      partners serve and shows how these functions contribute to health and survival
      for patients with HIV/AIDS. Ninety-eight minimally structured interviews were
      conducted with twenty pairs of adult HIV/AIDS patients (N = 20) and treatment
      partners (N = 20) treated at a public HIV-care setting in Tanzania. Four social
      functions were identified using inductive, category construction and interpretive
      methods of analysis: (1) encouraging disclosure; (2) combating stigma; (3)
      restoring hope; and (4) reducing social difference. These functions work to
      restore social connections and reverse the isolating effects of HIV/AIDS,
      strengthening access to essential community safety nets. Besides encouraging ARV
      adherence, treatment partners contribute to the social health of patients. Social
      health as well as HIV treatment success is essential to survival for persons
      living with HIV/AIDS in sub-Saharan Africa.

PMID- 21947836
TI  - HIV incidence among non-pregnant women living in selected rural, semi-rural and
      urban areas in KwaZulu-Natal, South Africa.
AB  - The province of KwaZulu-Natal has the highest prevalence of HIV in South Africa,
      particularly among young women. In order to more closely examine the HIV
      prevalence and incidence in non-pregnant women from rural, semi-rural and urban
      areas, data from 5,753 women screened for enrolment into three HIV prevention
      studies were combined and analysed. The prevalence of HIV infection was 43% at
      screening. HIV incidence among the 2,523 enrolled HIV-negative women was
      determined every quarter, and sexual behaviour and socio-demographic data were
      collected as per respective protocols. During follow-up, 211 women seroconverted
      (6.6/100 women years). Multivariate analysis found that seroconversion rates were
      highest among women who were <=24 years old, single and not cohabiting, and who
      had incident sexually transmitted infections. The epidemic in KwaZulu-Natal calls
      for targeted HIV prevention interventions among those at highest risk of
      acquiring or transmitting infection.

PMID- 21947837
TI  - Alternative SAIL-Trp for robust aromatic signal assignment and determination of
      the chi(2) conformation by intra-residue NOEs.
AB  - Tryptophan (Trp) residues are frequently found in the hydrophobic cores of
      proteins, and therefore, their side-chain conformations, especially the precise
      locations of the bulky indole rings, are critical for determining structures by
      NMR. However, when analyzing [U-(13)C,(15)N]-proteins, the observation and
      assignment of the ring signals are often hampered by excessive overlaps and tight
      spin couplings. These difficulties have been greatly alleviated by using stereo
      array isotope labeled (SAIL) proteins, which are composed of isotope-labeled
      amino acids optimized for unambiguous side-chain NMR assignment, exclusively
      through the (13)C-(13)C and (13)C-(1)H spin coupling networks (Kainosho et al. in
      Nature 440:52-57, 2006). In this paper, we propose an alternative type of SAIL
      Trp with the [zeta2,zeta3-(2)H(2); delta1,epsilon3,eta2-(13)C(3); epsilon1-(15)N]
      indole ring ([(12)C (gamma,) ( 12) C(epsilon2)] SAIL-Trp), which provides a more
      robust way to correlate the (1)H(beta), (1)H(alpha), and (1)H(N) to the
      (1)H(delta1) and (1)H(epsilon3) through the intra-residue NOEs. The assignment of
      the (1)H(delta1)/(13)C(delta1) and (1)H(epsilon3)/(13)C(epsilon3) signals can
      thus be transferred to the (1)H(epsilon1)/(15)N(epsilon1) and
      (1)H(eta2)/(13)C(eta2) signals, as with the previous type of SAIL-Trp, which has
      an extra (13)C at the C(gamma) of the ring. By taking advantage of the
      stereospecific deuteration of one of the prochiral beta-methylene protons, which
      was (1)H(beta2) in this experiment, one can determine the side-chain conformation
      of the Trp residue including the chi(2) angle, which is especially important for
      Trp residues, as they can adopt three preferred conformations. We demonstrated
      the usefulness of [(12)C(gamma),(12)C(epsilon2)] SAIL-Trp for the 12 kDa DNA
      binding domain of mouse c-Myb protein (Myb-R2R3), which contains six Trp
      residues.

PMID- 21947838
TI  - Interactions of protein side chains with RNA defined with REDOR solid state NMR.
AB  - Formation of the complex between human immunodeficiency virus type-1 Tat protein
      and the transactivation response region (TAR) RNA is vital for transcriptional
      elongation, yet the structure of the Tat-TAR complex remains to be established.
      The NMR structures of free TAR, and TAR bound to Tat-derived peptides have been
      obtained by solution NMR, but only a small number of intermolecular NOEs could be
      identified unambiguously, preventing the determination of a complete structure.
      Here we show that a combination of multiple solid state NMR REDOR experiments can
      be used to obtain multiple distance constraints from (15)N to (13)C spins within
      the backbone and side chain guanidinium groups of arginine in a Tat-derived
      peptide, using (19)F spins incorporated into the base of U23 in TAR and (31)P
      spins in the P22 and P23 phosphate groups. Distances between the side chain of
      Arg52 and the base and phosphodiester backbone near U23 measured by REDOR NMR are
      comparable to distances observed in solution NMR-derived structural models,
      indicating that interactions of TAR RNA with key amino acid side chains in Tat
      are the same in the amorphous solid state as in solution. This method is
      generally applicable to other protein-RNA complexes where crystallization or
      solution NMR has failed to provide high resolution structural information.

PMID- 21947840
TI  - Terena Amerindian group autosomal STR data: comparison studies with other
      Brazilian populations.
AB  - Allele frequencies for the high polymorphic short tandem repeats (STR) loci
      PentaE, PentaD, D18S51, D21S11, TH01, D3S1358, FGA, D16S539, D7820, D13S317, vWA
      and D81179 were analysed in an native Amerindian population from Mato Grosso do
      Sul state named Terena. Deviations from Hardy-Weinberg expectations were
      evaluated and the results showed no differences from equilibrium in all loci. The
      combined power of discrimination and the combined power of exclusion for the 12
      tested STR loci were 0.99999999 and 0.999999 respectively. The Terena population
      data were compared to other from 11 Brazilian populations (Amazonia, Pernambuco,
      Mato Grosso do Sul, Sao Paulo, Rio Grande do Sul, Alagoas, Sergipe, Rio Grande do
      Norte, Santa Catarina, Rondonia and Rio de Janeiro) representing the major
      Brazilian geographic regions. The F(ST) comparative analysis showed no
      significant differences between all those populations except when comparing
      Terena with the remained ones.

PMID- 21947839
TI  - Analysis of multiple polymorphisms in the bovine neuropeptide Y5 receptor gene
      and structural modelling of the encoded protein.
AB  - The neuropeptide Y 5 receptor (NPY5R) plays an important role in the regulation
      of appetite and feeding behaviour in mammals by modulating the effect of the
      neurotransmitter neuropeptide Y. As single nucleotide polymorphism (SNP)
      variation in the bovine NPY5R gene is likely to influence the expression and/or
      function of this gene, the objectives of this study were to identify SNPs in the
      bovine NPY5R gene and to predict their functional role in the expression and
      physico-chemical characteristics of the protein product. Nineteen novel SNPs were
      identified in a 2.1 kb genomic region of the NPY5R gene in a total of 419 beef
      cattle from 13 Bos taurus breeds and eight Bos indicus animals. Four of these
      SNPs were non-synonymous (Met -> Ile, Leu -> Phe, Pro -> Leu, Arg -> Stop codon),
      while 10 were synonymous. Of particular interest was one non-synonymous SNP
      (c.1090C>T) that introduced a stop codon in the third intracellular loop of the
      NPY5R molecule. This stop codon is predicted to create a truncated NPY5R molecule
      with different physico-chemical properties compared to the native NPY5R protein.
      A further four SNPs were located in the 5' untranslated region (UTR) and one in
      the 3'UTR. Two of the 5'UTR SNPs affected putative transcription factor binding
      sites (GATA binding factor and snRNA-activating protein complex). In conclusion,
      regulatory and functional SNPs were identified in the bovine NPY5R gene. These
      include SNPs which potentially modify transcription factor binding sites as well
      as SNPs that cause amino acid changes and premature termination of the NPY5R
      protein. Such polymorphisms are likely to play vital physiological roles in the
      neuropeptide Y mediated appetite, feed intake and energy homeostasis in cattle.

PMID- 21947841
TI  - Molecular characterization of a novel 14-3-3 protein gene (Hb14-3-3c) from Hevea
      brasiliensis.
AB  - The cDNA encoding a 14-3-3 protein, designated as Hb14-3-3c, was isolated from
      Hevea brasiliensis. Hb14-3-3c was 1,269 bp long containing a 795 bp open reading
      frame encoding a putative protein of 264 amino acids, flanked by a 146 bp 5'UTR
      and a 328 bp 3' UTR. The predicted molecular mass of Hb14-3-3c is 29.67 kDa, with
      an isoelectric point of 4.52 and the deduced protein showed high similarity to
      the 14-3-3 protein from other plant species. Expression analysis revealed more
      significant accumulation of Hb14-3-3c transcripts in latex than in leaves, buds
      and flowers. The transcription of Hb14-3-3c in latex was induced by jasmonate and
      ethephon. Overproduction of recombinant Hb14-3-3c protein gave the Escherichia
      coli cells more tolerance on Co(2+), Cu(2+) and Zn(2+). Through yeast two-hybrid
      screening, 11 interaction partners of the Hb14-3-3c, which are involved in rubber
      biosynthesis, stress-related responses, defence etc., were identified in rubber
      tree latex. Taking these data together, it is proposed that the Hb14-3-3c may
      participate in regulation of rubber biosynthesis. Thus, the results of this study
      provide novel insights into the 14-3-3 signaling related to rubber biosynthesis,
      stress-related responses in rubber tree.

PMID- 21947843
TI  - Has-miR-146a polymorphism (rs2910164) and cancer risk: a meta-analysis of 19 case
      control studies.
AB  - Epidemiological studies have evaluated the association between has-miR-146a
      polymorphism (rs2910164) and cancer risk. However, published data are still
      inconclusive. Here, we performed a meta-analysis to assess the relationship
      between has-miR-146a polymorphism (rs2910164) and cancer susceptibility until May
      8, 2010. Nineteen published case-control studies including a total of 10,496
      cases and 12,885 controls were acquired. Overall, Increased cancer risk was found
      in domain model (OR = 1.18, 95% CI: 1.03-1.35) rather than in other genetic
      models when all studies were pooled into the meta-analysis. Stratified analysis
      shown that significant association between rs2910164 polymorphism and cancer
      susceptibility was present in Asians (OR = 1.14, 95% CI: 1.01-1.29 for CG vs. CC;
      OR = 1.19, 95% CI: 1.03-1.39 for GG + CG vs. CC), but not in Caucasian
      populations. In the subgroup analysis by cancer types, no significantly increased
      risk of breast, gastric, prostate or bladder cancer were found in any of the
      genetic models. In summary, this meta-analysis suggests that has-miR-146a
      polymorphism (rs2910164) is associated with increased cancer susceptibility in
      Asians. However, further well-designed studies with large sample size will be
      necessary to validate the risk identified in the current meta-analysis.

PMID- 21947842
TI  - RecQ helicases; at the crossroad of genome replication, repair, and
      recombination.
AB  - DNA helicases are ubiquitous enzymes that unwind double-stranded DNA in an ATP
      dependent and directionally specific manner. Such an action is essential for the
      processes of DNA repair, recombination, transcription, and DNA replication. Here,
      I focus on a subgroup of DNA helicases, the RecQ family, which is highly
      conserved in evolution. Members of this conserved family of proteins have a key
      role in protecting and stabilizing the genome against deleterious changes.
      Deficiencies in RecQ helicases can lead to high levels of genomic instability
      and, in humans, to premature aging and increased susceptibility to cancer. Their
      diverse roles in DNA metabolism, which include a role in telomere maintenance,
      reflect interactions with multiple cellular proteins, some of which are
      multifunctional and also have very diverse functions. In this review, protein
      structural motifs and the roles of different domains will be discussed first. The
      Review moves on to speculate about the different models to explain why RecQ
      helicases are required to protect against genome instability.

PMID- 21947844
TI  - Resveratrol ameliorates oxidative DNA damage and protects against acrylamide
      induced oxidative stress in rats.
AB  - Acrylamide (ACR), used in many fields from industrial manufacturing to laboratory
      personnel work is also formed during the heating process through interactions of
      amino acids. Therefore ACR poses a significant risk to human health. This study
      aimed to elucidate whether resveratrol (RVT) treatment could modulate ACR-induced
      oxidative DNA damage and oxidative changes in rat brain, lung, liver, kidney and
      testes tissues. Rats were divided into four groups as control (C); RVT (30 mg/kg
      i.p. dissolved in 0.9% NaCl), ACR (40 mg/kg i.p.) and RVT + ACR groups. After 10
      days rats were decapitated and tissues were excised. 8-hydroxydeoxyguanosine (8
      OHdG) is a biomarker of oxidative DNA damage. 8-OHdG content in the extracted DNA
      solution was determined by enzyme-linked immunosorbent assay method.
      Malondialdehyde (MDA), glutathione (GSH) levels and myeloperoxidase activity
      (MPO) were determined in tissues, while oxidant-induced tissue fibrosis was
      determined by collagen contents. Serum enzyme activities, cytokine levels,
      leukocyte apoptosis were assayed in plasma. As an indicator of oxidative DNA
      damage, 8-OHdG levels significantly increased in ACR group and this was reversed
      significantly by RVT treatment. In ACR group, GSH levels decreased significantly
      while the MDA levels, MPO activity and collagen content increased in the tissues
      suggesting oxidative organ damage. In RVT-treated ACR group, oxidant responses
      reversed significantly. Serum enzyme activities, cytokine levels and leukocyte
      late apoptosis which increased following ACR administration, decreased with RVT
      treatment. Therefore supplementing with RVT can be useful in individuals at risk
      of ACR toxicity.

PMID- 21947845
TI  - Genetic variation at mtDNA and microsatellite loci in Chinese longsnout catfish
      (Leiocassis longirostris).
AB  - Genetic variability and population structure of the Chinese longsnout catfish
      Leiocassis longirostris Gunther in the Yangtze River was examined with
      mitochondrial control region sequences and nuclear microsatellite markers. A 705
      bp segment of the mitochondrial DNA control region was sequenced from 132
      samples, which identified a total of 61 haplotypes. The Chinese longsnout catfish
      in the Yangtze River was characterized with high haplotype diversity (h = 0.9770
      +/- 0.0041) but low nucleotide diversity (pi = 0.0081 +/- 0.0043). Median-joining
      network analysis revealed a star-shaped pattern and mismatch distribution
      analysis found a smooth unimodal distribution, which suggested that this species
      in the Yangtze River underwent a population expansion following bottlenecks
      and/or they originated from a small size of founding population. It was estimated
      that the possible time of population expansion was 139,000-435,000 years before
      present, a time period in the middle Pleistocene. The analysis of molecular
      variance and phylogenetic reconstructions did not detect significant geographic
      structure between different river sections. This pattern of genetic variation was
      further evidenced with nuclear microsatellite markers. The genetic
      differentiation between above and below the Gezhouba Dam and Three Gorges Dam is
      very small at mitochondrial and nuclear levels, which suggested that these
      recently developed dams might have not significantly resulted in population
      genetic fragmentation in the Chinese longsnout catfish. However, the potential
      exacerbation of genetic structuring by the dams should not be overlooked in the
      future.

PMID- 21947846
TI  - Ectopic expression of a LEA protein gene TsLEA1 from Thellungiella salsuginea
      confers salt-tolerance in yeast and Arabidopsis.
AB  - Thellungiella salsuginea is a valuable halophytic genetic model plant in the
      Brassicaceae family. Based on previous construction of a salt treated
      Thellungiella cDNA library carried by pGAD-GH shuttle vector which could directly
      express in Saccharomyces cerevisiae, a putative salt-tolerance gene TsLEA1 was
      identified by large-scale stress-tolerance screen in salt sensitive yeast strain
      G19. The longest 483 bp ORF of TsLEA1 cDNA coding a 160 amino acids protein with
      a predicted conserved pfam domain shared an 89% amino acid sequence similarity to
      Arabidopsis LEA group 4 proteins. The transcription level of TsLEA1 gene in T.
      salsuginea seedlings increased upon salt treatment and its transcript accumulated
      more in roots than in aerial parts. The ability of the TsLEA1 to facilitate
      salinity tolerance was analyzed in yeast and transgenic Arabidopsis. It was
      confirmed that TsLEA1 exhibits conserved salt tolerance in plant as well as in
      yeast. The results suggested that the TsLEA1 may participate in response to
      stresses in over expressed circumstance, protecting yeast and plant cells under
      stress conditions.

PMID- 21947847
TI  - H. pylori related proinflammatory cytokines contribute to the induction of miR
      146a in human gastric epithelial cells.
AB  - MicroRNAs have been implicated as a central regulator of the immune system. We
      have previously reported that Helicobacter pylori (H. pylori) was able to
      increase the expression of miR-146a, and miR-146a may negatively regulate H.
      pylori-induced inflammation, but the exact mechanism of how H. pylori contribute
      the induction of miR-146a is not clear. Here, we attempted to assess the role of
      H. pylori related proinflammatory cytokines including interleukin (IL)-8, tumor
      necrosis factor (TNF)-alpha, and interleukin (IL)-1beta, and cytotoxin-associated
      gene A (CagA) virulence factor on the induction of miR-146a. We found that IL-8,
      TNF-alpha, and IL-1beta could contribute to the induction of miR-146a in gastric
      epithelial cell HGC-27 in NF-kappaB-dependent manner, while the induction of miR
      146a upon H. pylori stimulation was independent of above proinflammatory
      cytokines. Furthermore, overexpression of miR-146a reduced H. pylori-induced IL
      8, TNF-alpha, and IL-1beta. However, CagA had no effect on the miR-146a
      induction. Taken together, our study suggest that proinflammatory cytokines IL-8,
      TNF-alpha, and IL-1beta could contribute to the induction of miR-146a during H.
      pylori infection, while CagA is not necessarily required for miR-146a induction.
      miR-146a may function as novel negative regulators to modulate the inflammation.

PMID- 21947848
TI  - Analysis of new lactotransferrin gene variants in a case-control study related to
      periodontal disease in dog.
AB  - The molecular and genetic research has contributed to a better understanding of
      the periodontal disease (PD) in humans and has shown that many genes play a role
      in the predisposition and progression of this complex disease. Variations in
      human lactotransferrin (LTF) gene appear to affect anti-microbial functions of
      this molecule, influencing the PD susceptibility. PD is also a major health
      problem in small animal practice, being the most common inflammatory disease
      found in dogs. Nevertheless, the research in genetic predisposition to PD is an
      unexplored subject in this species. This work aims to contribute to the
      characterization of the genetic basis of canine PD. In order to identify genetic
      variations and verify its association with PD, was performed a molecular analysis
      of LTF gene in a case-control approach, including 40 dogs in the PD cases group
      and 50 dogs in the control group. In this study were detected and characterized
      eight new single nucleotide variations in the dog LTF gene. Genotype and allele
      frequencies of these variations showed no statistically significant differences
      between the control and PD cases groups. Our data do not give evidence for the
      contribution of these LTF variations to the genetic background of canine PD.
      Nevertheless, the sequence variant L/15_g.411C > T leads to an aminoacid change
      (Proline to Leucine) and was predicted to be possibly damaging to the LTF
      protein. Further investigations would be of extreme value to clarify the
      biological importance of these new findings.

PMID- 21947849
TI  - Mitochondrial genetic background plays a role in increasing risk to asthma.
AB  - A number of studies suggest that mitochondrial dysfunction plays a role in the
      pathogenesis of asthma. To shed light for the first time on the role of the
      mitochondrial genome in the etiology of asthma we analyzed the mitochondrial tRNA
      genes and part of their flanking regions in patients with asthma compared with a
      set of healthy controls. We found a total of 10 mutations in 56 out of 76
      asthmatic patients. Four of these mutations were not found in the control group,
      five were observed at a significantly lower frequency in controls, but none of
      the combinations of mutations detected in asthma patients was observed in the
      controls. Furthermore, we observed that 27.6% of the asthma patients (vs. 4% of
      the controls) belonged to the haplogroup U (Fisher test P = 0.00) and a positive
      significant correlation was found between the occurrence of the haplogroup U and
      the severity of the disease (Fisher test P = 0.02). Whereas further studies in
      larger cohorts are needed to confirm these observations we suggest that the
      mitochondrial genetic background plays a key role in asthma development.

PMID- 21947850
TI  - Fluvastatin inhibits angiotensin II-induced nuclear factor kappa B activation in
      renal tubular epithelial cells through the p38 MAPK pathway.
AB  - 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors has been
      shown to reduce the progression of renal disease independent of cholesterol
      lowering effect, but the mechanism of potential protective effect remains
      unclear. Here, we investigate the effect of fluvastatin on activation of nuclear
      factor-kappaB (NF-kappaB) induced by angiotensin II (AngII) in rat kidney tubule
      epithelial cells (NRK-52E). Electrophoretic mobility shift assays (EMSA) was used
      to detect NF-kappaB activation. Phosphorylation of cellular p38 mitogen-activated
      protein kinase (p38MAPK) was determined by western blot analysis. AngII
      stimulated the DNA-binding activity of NF-kappaB and phosphorylation of p38MAPK
      in cultured NRK-52E cells in a dose-dependent (10(-9)-10(-6) mol/l) manner (P <
      0.01). AngII (10(-6) mol/l) induced a rapid (5 min) increase of the p38MAPK
      phosphorylation. NF-kappaB DNA-binding activity was increased at as early as 30
      min, peaked at 2 h after AngII treatment. This stimulatory effect of AngII on NF
      kappaB was blocked by SB203580 (a specific inhibitor of p38MAPK). Incubation of
      cells with fluvastatin significantly inhibited the AngII-induced NF-kappaB
      activation in a dose-dependent (10(-7)-10(-5) mol/l) manner (P < 0.05). Exogenous
      mevalonate (10(-4)mol/l) prevented the effect of fluvastatin on NF-kappaB
      activation. These results suggest the fluvastatin reduced AngII-induced NF-kappaB
      activation via the p38MAPK pathway in NRK-52E cells. The effect is at least
      partly due to blocking the biosynthesis of mevalonate.

PMID- 21947852
TI  - Effect of surgical castration on expression of TRPM8 in urogenital tract of male
      rats.
AB  - Trpm8 (melastatin-related transient receptor potential member 8), a member of the
      transient receptor potential (TRP) superfamily, encoding a cation channel named
      TRPM8, has been shown to be a primary androgen-responsive gene and play an
      important role in prostate physiology. To investigate the expression feature of
      TRPM8 in urogenital tract of male rats, and whether TRPM8 was also regulated by
      androgen receptor in these organs, male Sprague-Dawley rats were divided into
      three groups of 35 animals as follows: sham-operated (SHAM), orchidectomized
      (ORX), orchidectomized plus DHT treatment (O + D). Organs in urogenital tract,
      including kidney, prostate, seminal vesicle (SV), testis, epididymis and penis,
      were collected at different post-castration periods. RT-PCR, real-time PCR and
      Western blotting were used to detect the expression of androgen receptor (AR) and
      trpm8 in these tissue. As a result, AR and trpm8 can be detected in all these
      organs at mRNA or/and protein level. The mRNA expression of trpm8 in kidney,
      prostate, SV and penis decreased 24 or 72 h after castration and kept decreasing
      in a time-dependant manner. However, treatment of dihydrotestosterone (DHT) could
      reverse the effect of surgical castration. Collectively, our data provide
      evidence that TRPM8 and AR were expressed generally in urogenital tract of male
      rats, and in these organs, expression of trpm8 was regulated by serum androgen.

PMID- 21947851
TI  - Anti-inflammatory and immunomodulatory efficacy of indigenous probiotic
      Lactobacillus plantarum Lp91 in colitis mouse model.
AB  - Probiotics can affect the immune homeostasis by altering the gut microbial
      balance and enhancing the immune system of gut, thus benefits in Inflammatory
      Bowel Disease, including Crohn's disease and Ulcerative colitis. Relative gene
      expression of pro, anti-inflammatory cytokines and other molecules in 2,4,6
      trinitrobenzene sulfonic acid-induced colitis mouse model against Lactobacillus
      plantarum Lp91 (L. plantarum Lp91) was investigated by reverse transcription
      quantitative PCR (RT-qPCR) using relative expression software tool (REST 2008
      V2.0.7). L. plantarum Lp91 evoked significant down regulation of TNF-alpha and
      COX2 to 0.026 and 0.077 fold in colitis mouse model. No significant difference in
      expression of IL-12a cytokine in colitis mouse challenged with L. plantarum Lp91
      was also observed. IL-10 was significantly up-regulated to 37.813 and 1.327 fold
      in colitis and non-colitis mouse challenged with L. plantarum Lp91. While, other
      anti-inflammatory markers i.e. COX1, IL-4 and IL-6 were significantly up
      regulated in colitis mouse challenged with L. plantarum Lp91. MUC2 gene was
      significantly up regulated to 2.216 fold in non-colitis group. L. plantarum Lp91,
      an indigenous probiotic culture, the main subject of this project exhibited
      strong immunemodulatory properties under in vivo conditions in mouse colitis
      model.

PMID- 21947853
TI  - Catalase -262C>T polymorphisms in Hungarian vitiligo patients and in controls:
      further acatalasemia mutations in Hungary.
AB  - Catalase is the main regulator of hydrogen peroxide metabolism. In vitiligo
      patients there are conflicting data on its activity and no data on the effect of 
      262C>T polymorphism in the catalase gene. Blood catalase activity, -262C>T
      polymorphism and acatalasemia mutations were examined in 75 vitiligo patients and
      in 162 controls, in Hungary. We measured blood catalase activity and conducted
      analyses with PCR-SSCP, polyacrylamide gel electrophoresis and silver staining in
      combination with RFLP and nucleotide sequencing. Comparison of the wild (CC)
      genotype and the mutant (TT) genotype in the vitiligo patients revealed a non
      significant (P > 0.19) increase in blood catalase. Male controls with the CT
      genotype had significantly (P < 0.04) lower blood catalase activity than CC
      genotype controls. Female vitiligo patients with CC genotype had lower (P < 0.04)
      blood catalase than female controls. The frequency of wild genotype (CC) and C
      alleles is significantly (P < 0.04) decreased in Hungarian controls when compared
      to controls in Slovenia, Morocco, UK, Greece, Turkey, USA, China. The detection
      of a novel acatalasemia mutation (37C>T in exon 9) and the 113G>A (exon 9)
      mutation in Hungary are further proofs of genetic heterogeneity origin of
      acatalasemia mutations. In conclusion, the -262 C>T polymorphism has a reverse
      effect on blood catalase in vitiligo patients and in controls. In controls the
      mutant genotypes and alleles are more frequent in Hungary than in several other
      populations. The new acatalasemia mutations are further examples of heterogeneity
      of acatalasemia.

PMID- 21947854
TI  - Curcumin inhibits metastatic progression of breast cancer cell through
      suppression of urokinase-type plasminogen activator by NF-kappa B signaling
      pathways.
AB  - Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), is
      extracted from the plant Curcuma longa. It was recently reported for its
      anticancer effect on several types of cancer cells in vitro however, the
      molecular mechanisms of this anticancer effect are not fully understood. In the
      present study, we evaluated the effects of curcumin on human mammary epithelial
      carcinoma MCF-7 cells. Cells were treated with curcumin and examined for cell
      viability by MTT assay. The cells invasion was demonstrated by transwell assay.
      The binding activity of NF-kappaB to DNA was examined in nuclear extracts using
      Trans-AM NF-kappaB ELISA kit. Western blot was performed to detect the effect of
      curcumin on the expression of uPA. Our results showed that curcumin dose
      dependently inhibited (P < 0.05) the proliferation of MCF-7 cells. Meanwhile, the
      adhesion and invasion ability of MCF-7 cells were sharply inhibited when treated
      with different concentrations of curcumin. Curcumin also significantly decreased
      (P < 0.05) the expression of uPA and NF-kappaB DNA binding activity,
      respectively. It is concluded that curcumin inhibits the adhesion and invasion of
      MCF-7 cells through down-regulating the protein expression of uPA via of NF
      kappaB activation. Accordingly, the therapeutic potential of curcumin for breast
      cancer deserves further study.

PMID- 21947855
TI  - A methodological perspective on genetic risk prediction studies in type 2
      diabetes: recommendations for future research.
AB  - Fueled by the successes of genome-wide association studies, numerous studies have
      investigated the predictive ability of genetic risk models in type 2 diabetes. In
      this paper, we review these studies from a methodological perspective, focusing
      on the variables included in the risk models as well as the study designs and
      populations investigated. We argue and show that differences in study design and
      characteristics of the study population have an impact on the observed predictive
      ability of risk models. This observation emphasizes that genetic risk prediction
      studies should be conducted in those populations in which the prediction models
      will ultimately be applied, if proven useful. Of all genetic risk prediction
      studies to date, only a few were conducted in populations that might be relevant
      for targeting preventive interventions.

PMID- 21947856
TI  - Advances and current state of the security and privacy in electronic health
      records: survey from a social perspective.
AB  - E-Health systems are experiencing an impulse in these last years, when many
      medical agencies began to include digital solutions into their platforms.
      Electronic Health Records (EHRs) are one of the most important improvements,
      being in its most part a patient-oriented tool. To achieve a completely
      operational EHR platform, security and privacy problems have to be resolved, due
      to the importance of the data included within these records. But given all the
      different methods to address security and privacy, they still remain in most
      cases as an open issue. This paper studies existing and proposed solutions
      included in different scenarios, in order to offer an overview of the current
      state in EHR systems. Bibliographic material has been obtained mainly from
      MEDLINE and SCOPUS sources, and over 30 publications have been analyzed. Many EHR
      platforms are being developed, but most of them present weaknesses when they are
      opened to the public. These architectures gain significance when they cover all
      the requisites related to security and privacy.

PMID- 21947857
TI  - Cd and Pb contents in soil, plants, and grasshoppers along a pollution gradient
      in Huludao City, Northeast China.
AB  - Cd and Pb contents in soil, plants, and two grasshopper species (Locusta
      migratoria manilensis and Acrida chinensis) were examined to quantify the
      influence ranges of zinc smelting on heavy metal contamination. Samples were
      collected simultaneously from Huludao City, a chemical and nonferrous smelting
      base in Northeast China. Cd and Pb contamination in soil and plants were serious.
      Cd and Pb contents were 13.32 and 8.83 mg/kg in L. migratoria manilensis and
      16.67 and 15.00 mg/kg in A. chinensis, respectively. Correlation analysis
      indicated the same metal source for Cd and Pb in soil, plants, and grasshoppers.
      Cd and Pb contents in soil, plants, and grasshoppers were all significantly
      related to distances far from the zinc smelter in good negative logarithm model.
      The fitting curves indicated that the influence radius of the smelter on heavy
      metal contamination was about 4,000 m for soil and plants and about 2,000 m for
      grasshoppers.

PMID- 21947858
TI  - The effect of calcium on non-heme iron uptake, efflux, and transport in
      intestinal-like epithelial cells (Caco-2 cells).
AB  - It has been suggested that calcium inhibits the absorption of dietary iron by
      directly affecting enterocytes. However, it is not clear if this effect is due to
      a decreased uptake of iron or its efflux from enterocytes. We studied the effect
      of calcium on the uptake, efflux, and net absorption of non-heme iron using the
      intestinal-like epithelial cell line Caco-2 as an in vitro model. Caco-2 cells
      were incubated for 60 min in a buffer supplemented with non-heme iron (as
      sulfate) and calcium to achieve calcium to iron molar ratios ranging from 50:1 to
      1,000:1. The uptake, efflux, and net absorption of non-heme iron were calculated
      by following a radioisotope tracer of (55)Fe that had been added to the buffer.
      Administration of calcium and iron at molar ratios between 500 and 1,000:1
      increased the uptake of non-heme iron and decreased efflux. Calcium did not have
      an effect on the net absorption of non-heme iron. At typical supplementary doses
      for calcium and non-heme iron, calcium may not have an effect on the absorption
      of non-heme iron. The effect of higher calcium to iron molar ratios on the efflux
      of non-heme iron may be large enough to explain results from human studies.

PMID- 21947859
TI  - Effect of selenium, zinc, and copper supplementation on blood metabolic profile
      in male buffalo (Bubalus bubalis) calves.
AB  - Twenty male buffalo calves (15 months, 200.2 +/- 9.75) were divided into four
      groups of five animals in each and fed diets without (T1) or supplemented with
      0.3 ppm selenium (Se) + 40 ppm zinc (Zn) (T2), 0.3 ppm Se + 40 ppm Zn + 10 ppm
      copper (Cu) (T3), and 40 ppm Zn + 10 ppm Cu (T4) for 120 days, during which blood
      samples were collected on days 0, 40, 80, and 120. Concentrations of glucose,
      total protein, albumin, globulin, urea, uric acid, and creatinine were similar in
      all the four groups. The level of different serum enzymes viz. lactate
      dehydrogenase, alkaline phosphatase, glutamate pyruvate transaminase, and
      glutamate oxaloacetate transaminase, and hormones viz. T(3), T(4), testosterone
      and insulin were similar (P > 0.05) among the four groups but the ratio of
      T(4)/T(3) was reduced (P < 0.05) in the groups (T2 and T3) where selenium was
      supplemented at 120th day of supplementation. It was deduced that supplementation
      of 0.3 ppm Se and/or 10.0 ppm of Cu with 40 ppm Zn had no effect on blood
      metabolic profile in buffalo calves, except the ratio of T(4) and T(3) hormone
      which indicates that selenium plays an important role in converting T(4) hormone
      to T(3) which is more active form of thyroid hormone.

PMID- 21947860
TI  - Effects of stimulation of copper bioleaching on microbial community in vineyard
      soil and copper mining waste.
AB  - Long-term copper application in vineyards and copper mining activities cause
      heavy metal pollution sites. Such sites need remediation to protect soil and
      water quality. Bioremediation of contaminated areas through bioleaching can help
      to remove copper ions from the contaminated soils. Thus, the aim of this work was
      to evaluate the effects of different treatments for copper bioleaching in two
      diverse copper-contaminated soils (a 40-year-old vineyard and a copper mining
      waste) and to evaluate the effect on microbial community by applying denaturing
      gradient gel electrophoresis (DGGE) of 16S ribosomal DNA amplicons and DNA
      sequence analysis. Several treatments with HCl, H(2)SO(4), and FeSO(4) were
      evaluated by stimulation of bioleaching of copper in the soils. Treatments and
      extractions using FeSO(4) and H(2)SO(4) mixture at 30 degrees C displayed more
      copper leaching than extractions with deionized water at room temperature.
      Treatment with H(2)SO(4) supported bioleaching of as much as 120 mg kg(-1) of
      copper from vineyard soil after 115 days of incubation. DGGE analysis of the
      treatments revealed that some treatments caused greater diversity of
      microorganisms in the vineyard soil compared to the copper mining waste.
      Nucleotide Blast of PCR-amplified fragments of 16S rRNA gene bands from DGGE
      indicated the presence of Rhodobacter sp., Silicibacter sp., Bacillus sp.,
      Paracoccus sp., Pediococcus sp., a Myxococcales, Clostridium sp., Thiomonas sp.,
      a firmicute, Caulobacter vibrioides, Serratia sp., and an actinomycetales in
      vineyard soil. Contrarily, Sphingomonas was the predominant genus in copper
      mining waste in most treatments. Paracoccus sp. and Enterobacter sp. were also
      identified from DGGE bands of the copper mining waste. Paracoccus species is
      involved in the copper bioleaching by sulfur oxidation system, liberating the
      copper bounded in the soils and hence promoting copper bioremediation. Results
      indicate that stimulation of bioleaching with a combination of FeSO(4) and
      H(2)SO(4) promoted bioleaching in the soils and can be employed ex situ to
      remediate copper-impacted soils.

PMID- 21947861
TI  - Divalent metal transporter 1 expression and regulation in human placenta.
AB  - Divalent metal transporter 1 (DMT1) is likely responsible for the release of iron
      from endosomes to the cytoplasm in placental syncytiotrophoblasts (STB). To
      determine the localization and the regulation of DMT1 expression by iron directly
      in placenta, the expression of DMT1 in human term placental tissues and BeWo
      cells (human placental choriocarcinoma cell line) was detected and the change in
      expression in response to different iron treatments on BeWo cells was observed.
      DMT1 was shown to be most prominent near the maternal side in human term placenta
      and predominantly in the cytoplasm of BeWo cells. BeWo cells were treated with
      desferrioxamine (DFO) and human holotransferrin (hTf-2Fe) and it was found that
      both DMT1 mRNA and protein increased significantly with DFO treatment and
      decreased with hTf-2Fe treatment. Further, DMT1 mRNA responded more significantly
      to treatments if it possessed an iron-responsive element than mRNA without this
      element. This study indicated that DMT1 is likely involved in endosomal iron
      transport in placental STB and placental DMT1 + IRE expression was primarily
      regulated by the IRE/IRP mechanism.

PMID- 21947862
TI  - Metabolic fecal nitrogen and digestibility estimates in the grasscutter
      (Thryonomys swinderianus).
AB  - The metabolic fecal nitrogen and digestibility estimates in the grasscutter were
      determined using 12 captive-bred adult animals fed with four experimental diets
      differing primarily in crude protein content using nitrogen balance trial
      approach. Grasscutters required 343.5 mg N kg(-0.75) d(-1) of nitrogen to meet
      maintenance requirements, which were met on diets containing 7.4% crude protein.
      The true digestibility of nitrogen was moderate (52%) but within the range for
      eutherians. Dry matter intake increased with decreasing dietary nitrogen content,
      suggesting that animals on nitrogen-deficient diets displayed appreciable
      compensatory intake. Metabolic fecal nitrogen was 3.5 g N kg(-1) dry matter
      intake, and endogenous urinary nitrogen was 257.5 mg N kg(-0.75) d(-1). The low
      value of metabolic fecal nitrogen found for grasscutters affected the dry matter
      intake required for nitrogen balance, and it may allow grasscutters to exploit
      nitrogen poor diets.

PMID- 21947863
TI  - Comparative analysis of hatching rates and clutch sizes of Nile crocodile
      (Crocodylus niloticus) eggs collected on- and off-farm in Zimbabwe.
AB  - The Nile crocodile (Crocodylus niloticus) is a large aquatic reptile predominant
      in the tropics in Africa and Zimbabwe in particular. Clutch sizes and hatching
      rates of Nile crocodile eggs collected from the wild and on-farm in Lowveld,
      Highveld and Kariba regions of Zimbabwe were evaluated. A total of 274 egg
      records for the period 2000 to 2008 from 39 farms were collected from the
      Crocodile Farmers Association of Zimbabwe. The effect of source of eggs was
      analysed using the non-parametric one way analysis of variance procedure of SAS
      Version 9.1.3. Wilcoxon signed rank test for independent samples was used to
      compare the mean hatching rates and clutch sizes for eggs collected from the
      different sources by region. The degree of association between clutch sizes and
      the hatching rates by source and region was determined using the Spearman's rank
      correlation test. Source of eggs had no effect (P > 0.05) on hatching rates in
      all the regions but significantly influenced (P < 0.05) clutch sizes in Lowveld
      and Kariba. In these regions, clutch sizes in the wild were significantly (P <
      0.05) higher than those on-farm. Correlation estimates between clutch size and
      hatching rates were weak and non-significant (P > 0.05) for the different sources
      of eggs in all regions. Full utilization of the wild resource would reduce
      challenges relating to shortage of captive breeders and high cost of rearing
      breeders and hence increase productivity.

PMID- 21947864
TI  - Osteitis condensans ilii in differential diagnosis of patients with chronic low
      back pain: a review of the literature.
AB  - Osteitis condensans ilii (OCI) is a benign pathology causing chronic back and hip
      pain. Although the definitive cause is uncertain, mechanical stress is a
      significant factor in the development of the disease. Bilateral involvement of
      the sacroiliac joint is typical. We describe a case of unilateral OCI with
      unilateral sclerosis observed at radiography in a 34-year-old patient presenting
      with chronic back and hip pain, together with a review of the literature.

PMID- 21947866
TI  - Machine vision-based localization of nucleic and cytoplasmic injection sites on
      low-contrast adherent cells.
AB  - Automated robotic bio-micromanipulation can improve the throughput and efficiency
      of single-cell experiments. Adherent cells, such as fibroblasts, include a wide
      range of mammalian cells and are usually very thin with highly irregular
      morphologies. Automated micromanipulation of these cells is a beneficial yet
      challenging task, where the machine vision sub-task is addressed in this article.
      The necessary but neglected problem of localizing injection sites on the nucleus
      and the cytoplasm is defined and a novel two-stage model-based algorithm is
      proposed. In Stage I, the gradient information associated with the nucleic
      regions is extracted and used in a mathematical morphology clustering framework
      to roughly localize the nucleus. Next, this preliminary segmentation information
      is used to estimate an ellipsoidal model for the nucleic region, which is then
      used as an attention window in a k-means clustering-based iterative search
      algorithm for fine localization of the nucleus and nucleic injection site (NIS).
      In Stage II, a geometrical model is built on each localized nucleus and employed
      in a new texture-based region-growing technique called Growing Circles Algorithm
      to localize the cytoplasmic injection site (CIS). The proposed algorithm has been
      tested on 405 images containing more than 1,000 NIH/3T3 fibroblast cells, and
      yielded the precision rates of 0.918, 0.943, and 0.866 for the NIS, CIS, and
      combined NIS-CIS localizations, respectively.

PMID- 21947865
TI  - Opioid receptor trafficking and signaling: what happens after opioid receptor
      activation?
AB  - Prolonged opioid treatment leads to a comprehensive cellular adaptation mediated
      by opioid receptors, a basis to understand the development of opioid tolerance
      and dependence. However, the molecular mechanisms underlying opioid-induced
      cellular adaptation remain obscure. Recent advances in opioid receptor
      trafficking and signaling in cells have extensively increased our insight into
      the network of intracellular signal integration. This review focuses on those
      important intracellular biochemical processes that play critical roles in the
      development of opioid tolerance and dependence after opioid receptor activation,
      and tries to explain what happens after opioid receptor activation, and how the
      cellular adaptation develops from cell membrane to nucleus. Decades of research
      have delineated a network on opioid receptor trafficking and signaling, but the
      challenge remains to explain opioid tolerance and dependence from a single
      cellular signal network.

PMID- 21947867
TI  - Compressive sensing scalp EEG signals: implementations and practical performance.
AB  - Highly miniaturised, wearable computing and communication systems allow
      unobtrusive, convenient and long term monitoring of a range of physiological
      parameters. For long term operation from the physically smallest batteries, the
      average power consumption of a wearable device must be very low. It is well known
      that the overall power consumption of these devices can be reduced by the
      inclusion of low power consumption, real-time compression of the raw
      physiological data in the wearable device itself. Compressive sensing is a new
      paradigm for providing data compression: it has shown significant promise in
      fields such as MRI; and is potentially suitable for use in wearable computing
      systems as the compression process required in the wearable device has a low
      computational complexity. However, the practical performance very much depends on
      the characteristics of the signal being sensed. As such the utility of the
      technique cannot be extrapolated from one application to another. Long term
      electroencephalography (EEG) is a fundamental tool for the investigation of
      neurological disorders and is increasingly used in many non-medical applications,
      such as brain-computer interfaces. This article investigates in detail the
      practical performance of different implementations of the compressive sensing
      theory when applied to scalp EEG signals.

PMID- 21947868
TI  - A longitudinal three-center study of craniofacial morphology at 6 and 12 years of
      age in patients with complete bilateral cleft lip and palate.
AB  - In this longitudinal study, the craniofacial morphology and evaluated soft tissue
      profile changes, at 6 and 12 years of age in patients with complete bilateral
      cleft lip and palate (CBCLP) were compared. Lateral cephalograms from 148
      patients with CBCLP, treated consecutively at three European cleft centers,
      Gothenburg (n (A) = 37), Nijmegen (n (B) = 26), and Oslo (n (C) = 85), were
      evaluated. Eighteen hard tissue and ten soft tissue landmarks were digitized.
      Paired t test, Pearson's correlation coefficients, and multiple regression models
      were applied for statistical analysis. ANOVA and Tukey-B, as a post hoc test,
      were used to evaluate the increments and compare centers. Hard and soft tissue
      data were superimposed using the generalized Procrustes analysis. For Nijmegen,
      the increments of the variables SNA, ANB, SN-NL, SN-ML, NL-ML, Snss, and Snpg
      were significantly different than the two other centers (p = 0.041 to <0.001).
      SNPg increments were significantly different between Nijmegen and Oslo (p =
      0.002). The three cleft centers followed different treatment protocols, but the
      main differences in craniofacial morphology until 12 years of age were the growth
      pattern and the maxillary and upper incisor variables. Follow-up of these
      patients until facial growth has ceased, which may elucidate components for
      improving treatment outcome.

PMID- 21947869
TI  - Posterior transdural discectomy: a new approach for the removal of a central
      thoracic disc herniation.
AB  - BACKGROUND: The optimal surgical approach for thoracic disc herniation remains a
      matter of debate, especially for central disc herniation. In this paper, we
      present a new technique to remove central thoracic disc herniation, the posterior
      transdural approach, and report a series of 13 cases operated on in this way at
      our institute. METHODS: Between September 2004 and October 2010, 13 patients with
      symptomatic central thoracic disc herniation were operated on, utilising this
      posterior transdural approach. All patients underwent magnetic resonance imaging
      (MRI) of the thoracic spine before surgery. All patients were followed at our
      outpatient department for at least 3 months. In addition, all patients were
      interviewed in April 2009 and February 2011 to evaluate the final results. A
      seven-point Likert scale was applied and the Frankel score was determined
      preoperatively and postoperatively. Additionally, a postoperative MRI was
      obtained for all but two patients. RESULTS: The most frequently involved levels
      were T10-11 and T12-L1. Median operative time was 210 min (range 140-360). Three
      patients experienced reversible complications. No patient required spinal
      fixation. The median duration of hospitalisation was 6 days (range 4-20 days).
      With a median follow-up of 18 months, symptoms improved in 12 patients (92%),
      including the three patients with complications. One patient was unchanged (8%),
      while none of the patients experienced worsening of symptoms. CONCLUSIONS: The
      posterior transdural approach is well tolerated by the patient and has a
      relatively high success rate. It is a relatively simple and safe procedure,
      suitable for the operative treatment of almost all types of thoracic disc
      herniation, but especially the centrally located disc herniation.

PMID- 21947870
TI  - Evaluation of the rate of decompression in anterior cervical corpectomy using an
      intra-operative computerized tomography scan (O-Arm system).
AB  - OBJECT: The purpose of this study was to evaluate the efficacy of intra-operative
      computerized tomography (CT) scanning in the analysis of bone removal accuracy
      during anterior cervical corpectomy, in order to allow any necessary immediate
      correction in the event of inadequate bone removal. METHODS: From September 2009
      to December 2010 we performed an intra-operative (CT) scan using the O-Arm(TM)
      Image system to assess the rate of central and lateral decompression in all
      patients treated for cervical spondylotic myelopathy by anterior cervical
      corpectomy and fusion. RESULTS: Out of a population of 187 patients admitted to
      our department, with a diagnosis of myelopathy due to spondylotic degenerative
      cervical stenosis, 15 patients underwent a surgical treatment with anterior
      cervical corpectomy and fusion. There were nine males (60%) and six females
      (40%); the mean age was 52.4 years, ranging from 41 to 57 years. The pre
      operative radiologic investigations (MRI and CT scans) revealed in the nine
      patients (60%) the extent of the compression to one vertebral body (C4 one case,
      C5 four cases, C6 four cases), while in the six cases (40%) the compression
      regarded two vertebral body (C3 and C4 one case, C4 and C5 two cases, C5 and C6
      three cases). During surgery, when the decompression was judged completely, a CT
      scan was performed: in 11 cases (73.3%) the decompression was considered
      adequate, while in four cases (26.7%) it was deemed insufficient and the surgical
      strategy was changed in order to optimize the bone removal. In these cases an
      additional scan was taken to prove the efficacy of decompression, achieved in all
      patients. CONCLUSION: Intra-operative CT scan performed during cervical
      corpectomy is a really useful tool in helping to ensure complete bone removal and
      the adequacy of surgery. The O-arm(TM) Image system grants optimal image quality,
      allowing correctly assessing the rate of decompression and, in any case of doubt,
      allows an intra-operative evaluation of the final correct positioning of the
      graft.

PMID- 21947871
TI  - 4D APSY-HBCB(CG)CDHD experiment for automated assignment of aromatic amino acid
      side chains in proteins.
AB  - A four-dimensional (4D) APSY (automated projection spectroscopy)-HBCB(CG)CDHD
      experiment is presented. This 4D experiment correlates aromatic with aliphatic
      carbon and proton resonances from the same amino acid side chain of proteins in
      aqueous solution. It thus allows unambiguous sequence-specific assignment of
      aromatic amino acid ring signals based on backbone assignments. Compared to
      conventional 2D approaches, the inclusion of evolution periods on (1)H(beta) and
      (13)C(delta) efficiently removes overlaps, and provides two additional
      frequencies for consequent automated or manual matching. The experiment was
      successfully applied to three proteins with molecular weights from 6 to 13 kDa.
      For the complementation of the assignment of the aromatic resonances, TOCSY- or
      COSY-based versions of a 4D APSY-HCCH(aro) sequence are proposed.

PMID- 21947873
TI  - Council-based approaches to reforming the health care response to domestic
      violence: promising findings and cautionary tales.
AB  - Councils are commonly formed to address social issues including intimate partner
      violence (IPV). Research suggests that councils may be well positioned to achieve
      proximal outcomes, but that their success may depend on contextual factors. The
      current study compared providers and health care settings at two points in time
      to explore the degree to which the Health Care Council achieved proximal outcomes
      in the health care response to IPV, including: (a) providers' reported capacity
      to screen for IPV, (b) providers' beliefs about IPV as a health care issue and
      about the IPV screening process, (c) providers' screening behaviors and (d)
      organizational policies and protocols to encourage screening. This study, while
      preliminary, provides support for council-based efforts to stimulate change in
      the health care response to IPV and also highlights the central role that
      organizational environment plays in shaping desired outcomes.

PMID- 21947872
TI  - NAD(P)H:quinone oxidoreductase 1 is induced by progesterone in cardiomyocytes.
AB  - NAD(P)H: quinone oxidoreductase 1 (NQO1) is a ubiquitous flavoenzyme that
      catalyzes two-electron reduction of various quinones by utilizing NAD(P)H as an
      electron donor. Our previous study found that progesterone (PG) can protect
      cardiomyocytes from apoptosis induced by doxorubicin (Dox). Microarray analyses
      of genes induced by PG had led to the discovery of induction of NQO1 mRNA. We
      report here that PG induces NQO1 protein and its activity in a dose-dependent
      manner. Whereas NQO1 is well known as a target gene of Nrf2 transcription factor
      due to the presence of antioxidant response element (ARE) in the promoter, PG did
      not activate the ARE, suggesting Nrf2-independent induction of NQO1. To address
      the role of NQO1 induction in PG-induced cytoprotection, we tested the effect of
      NQO1 inducer beta-naphthoflavone and inhibitor dicoumarol. Induction of NQO1 by
      beta-naphthoflavone decreased Dox-induced apoptosis and potentiated the
      protective effect of PG as measured by caspase-3 activity. PG-induced NQO1
      activity was inhibited with dicoumarol, which did not affect PG-induced
      cytoprotection. Dicoumarol treatment alone potentiated Dox-induced caspase-3
      activity. These data suggest that while NQO1 plays a role in PG-induced
      cytoprotection, there are additional components contributing to PG-induced
      cytoprotection.

PMID- 21947874
TI  - Changing the system by changing the workforce: employing consumers to increase
      access, cultural diversity, and engagement.
AB  - Services to families have traditionally been delivered in a medical model. This
      presents challenges including workforce shortages, lack of cultural diversity,
      lack of training in strength-based work, and difficulty in successfully engaging
      and retaining families in the therapy process. The system of care (SOC) effort
      has worked to establish formal roles for caregivers in SOC to improve services.
      This paper provides an example of one community's efforts to change the SOC by
      expanding the roles available to caregivers in creating systems change. It
      describes the model developed by Communities of Care (CoC), a SOC in Central
      Massachusetts, and its evolution over a 10 year period. First person accounts by
      system partners, caregivers hired into professional roles as well as a family
      receiving services, demonstrate how hiring caregivers at all levels can change
      systems and change lives, not only for those being served but for the
      caregiver/professionals doing the work. It also demonstrates, however, that
      change at the system level is incremental, takes time, and can be fleeting unless
      an ongoing effort is made to support and sustain those changes.

PMID- 21947875
TI  - High-resolution genomic profiling of an adult Wilms' tumor: evidence for a
      pathogenesis distinct from corresponding pediatric tumors.
AB  - Wilms' tumor (WT), the most common kidney tumor among children, is characterized
      by a triphasic morphology consisting of blastemal, epithelial, and stromal
      components. Adult WT is a rare malignancy displaying similar histological
      features. We here present the first published high-resolution genomic analysis of
      a mixed-type adult WT. This revealed a more pronounced genetic complexity than
      usually observed in children with mixed-type WT. The majority of chromosomes
      displayed uniparental disomies, and microdeletions were present in genes with
      known importance for tumor formation (LRP1B, FHIT, and WWOX) or organogenesis
      (NEGR1 and ZFPM2), abnormalities not previously reported for pediatric WT. Our
      results indicate that adult WT is a biological entity distinct from the
      corresponding pediatric tumor type.

PMID- 21947877
TI  - Monitoring of cotton dust and health risk assessment in small-scale weaving
      industry.
AB  - The present study describes the estimation of particulate matter (cotton dust)
      with different sizes, i.e., PM(1.0), PM(2.5), PM(4.0), and PM(10.0 MUm) in small
      scale weaving industry (power looms) situated in district Hafizabad, Punjab,
      Pakistan, and the assessment of health problems of workers associated with these
      pollutants. A significant difference was found in PM(1.0), PM(2.5), PM(4.0), and
      PM(10.0) with reference to nine different sampling stations with p values <0.05.
      Multiple comparisons of particulate matter with respect to size, i.e. PM(1.0),
      PM(2.5), PM(4.0), and PM(10.0), depict that PM(1.0) differs significantly from
      PM(2.5), PM(4.0), and PM(10.0), with p values <0.05 and that PM(2.5) differs
      significantly from PM(1.0) and PM(10.0), with p values <0.05, whereas PM(2.5)
      differs non-significantly from PM(4.0), with a p value >0.05 in defined sampling
      stations on an average basis. Majority of the workers were facing several
      diseases due to interaction with particulate matter (cotton dust) during working
      hours. Flue, cough, eye, and skin infections were the most common diseases among
      workers caused by particulate matter (cotton dust).

PMID- 21947876
TI  - Diagnosis and management of pernicious anemia.
AB  - Pernicious anemia is a macrocytic anemia due to cobalamin deficiency, which is
      the result of intrinsic factor deficiency. Pernicious anemia is associated with
      atrophic body gastritis, whose diagnostic criteria are based on the histologic
      evidence of gastric body atrophy associated with hypochlorhydria. Serological
      markers suggesting the presence of oxyntic mucosa damage are increased levels of
      fasting gastrin and decreased levels of Pepsinogen I. Without the now obsolete
      Schilling's test, intrinsic factor deficiency may not be proven, and gastric
      intrinsic factor output after pentagastric stimulation has been proposed.
      Intrinsic factor autoantibodies are useful surrogate markers of pernicious
      anemia. The management of patients with pernicious anemia should focus on the
      life-long replacement treatment with cobalamin and the monitoring to early
      diagnose an eventual onset of iron deficiency. Moreover, these patients should be
      advised about possible gastrointestinal long-term consequences, such as gastric
      cancer and carcinoids.

PMID- 21947878
TI  - Reaction kinetics and validity of BOD test for domestic wastewater released in
      marine ecosystems.
AB  - With urbanization of coastal cities, marine pollution is becoming a severe
      problem. The rates of biodegradation, decomposition, and ratification of
      pollutants get slowed down due to salinity. The higher temperatures prevalent in
      tropical regions significantly affect reaction rates. Multiple factors influence
      the rate of biodegradation, making the process complex. Hence, prediction and
      evaluation of the assimilative capacity of the marine environment due to
      wastewater discharges is becoming a difficult task. Biochemical oxygen demand
      (BOD) is a wet oxidation process, which follows first-order kinetics. The values
      of kinetic rate constants are expected to differ with varying salinities and
      temperatures. Research is carried out using glucose-glutamic acid and domestic
      wastewater to evaluate the impact of salinity on biodegradation of carbonaceous
      waste at 20 degrees C and 27 degrees C. The findings confirm the hypothesis of
      slow biodegradation of carbonaceous organic matter in marine waters. An inverse
      relationship between rate of biodegradation and salinity was observed. BOD
      exertion at 20 degrees C (5 days) and 27 degrees C (3 days) for the marine
      environment is comparable at selected salinities thereby confirming the validity
      of BOD test of shorter duration at elevated temperature.

PMID- 21947879
TI  - Bacterial community composition of sediments from artificial Lake Maslak,
      Istanbul, Turkey.
AB  - Small artificial lakes are ubiquitous in various natural environments. Small
      impoundments increase the residence time of water, thereby increasing the
      potential for retention of nutrients through biological and physical processes.
      We examined bacterial community structure of Lake Maslak, a small freshwater
      impoundment located in a densely populated region. The objective of our study was
      to investigate bacterial communities of the lake sediment which has not been
      determined and to elucidate the factors controlling bacterial diversity and the
      biogeochemical processes within the lake. For these purposes, surface water, lake
      bed sediments, and one core sample were collected. Microbiological characteristic
      of the lake bed and core sediments was determined by denaturing gradient gel
      electrophoresis targeting the 16S rRNA gene. Along with the microbiological
      studies, physicochemical (O(2), pH, temperature) and geochemical properties of
      the surface (NO (3) (-) , NO (2) (-) , NH (4) (+) ,PO (4) (-) ,SO (4) (2-) ,
      K(+), Mg(2+), Ca(2+)) and pore water (K(+), Mg(2+), Ca(2+)) were determined in
      addition to heavy metals contents (Co Cu, Fe, Zn, Pb, Cd). Eight lake bed and one
      core sediments were also collected and analyzed for heavy metals and elemental
      compositions. Nitrate concentration in the surface water ranges from 0.27-1.8
      mg/L, and ammonium (0.0-0.83 mg/L) appears to follow nitrate concentration.
      Sulfate concentration in the surface water (mean 60 mg/L) is greater than those
      measured in the pore water (mean, 37.5 mg/L). Fe, Zn, Pb, and Cd were not
      determined in the surface water, whereas Co was significantly higher both in the
      surface and pore water. Unlike Co, Pb, Zn, and Cd were not measured in the pore
      water. Lakebed and core sediments show significant enrichment in Pb, Zn, and Cu,
      indicating anthropogenic pollution. Consistent with geochemical parameters,
      microbiological analysis suggests a diverse bacterial community in the lake
      sediments and influence of anthropogenic pollution (e.g., atmospheric emission)
      on bacterial community.

PMID- 21947881
TI  - Is there any association between GLY82 ser polymorphism of rage gene and Turkish
      diabetic and non diabetic patients with coronary artery disease?
AB  - This study was carried out in 52 non-diabetic, 62 diabetic patients with coronary
      artery disease (CAD) and 55 controls. A Gly to Ser change RAGE gene was analyzed
      by PCR-RFLP techniques. GlyGly genotype frequency is higher in non-diabetics
      versus controls (P < 0.001). GlySer frequency is higher in diabetics than
      controls and non-diabetics (P < 0.001). Ser allele frequency is respectively
      increased in the order of diabetics > Controls > non-diabetics. These results
      reveals none association between Gly82Ser and the development of disease in non
      diabetic patients. In diabetics with Ser allele, higher prevalence of left
      ventricule-hypertrophy was observed, but the significant difference between
      Gly82Ser and left-ventricule-hypertrophy only found in the whole patient group.
      As a result Ser allele has much more importance in the development of left
      ventricule-hypertrophy than other cardiovascular risk factors. In this study we
      found the presence of Gly allele contributes to the CAD in non-diabetics and Ser
      allele may contribute to disease in diabetics.

PMID- 21947882
TI  - Expression analysis of MAP2K9 and MAPK6 during pathogenesis of Alternaria blight
      in Arabidopsis thaliana ecotype Columbia.
AB  - Arabidopsis thaliana ecotype Columbia was used as a host in order to investigate
      the involvement of MAP kinase machinery in the pathogenesis of Alternaria blight.
      Semi-quantitative reverse transcriptase polymerase chain reaction and
      quantitative real time PCR based approaches were used to determine the change in
      transcript profile of MAP2K9 and MAPK6 in leaves of A. thaliana ecotpe Columbia
      at early, middle and late stages of Alternaria blight infection. It was observed
      that the expression of both MAP2K9 and MAPK6 simultaneously increased up to
      middle stage of disease progression. There was observed a positive correlation
      between the expression of MAPK6 and MAP2K9 as disease progressed from initial to
      middle stage of infection. Then, the expression of MAP2K9 decreased and that of
      MAPK6 increased as disease progressed towards late stage of infection. The
      increased levels of MAP2K9 and MAPK6, seem to be necessary for plant to defend
      the pathogen up to middle stage of infection. However, MAP2K9 may be down
      regulated at late stage of infection by pathogen to promote it's efficient
      colonization. Since MAPK6 expression remains unaltered till late stage, it
      suggests that it's expression is not only regulated by MAP2K9 but also by other
      MAP2K's. The above results are consistent with observations of earlier studies.
      In conclusion, the present study has suggested MAP2K9/MAPK6 module as possible
      target, which is influenced during pathogenesis of Alternaria blight in A.
      thaliana ecotype Columbia. Hence genetic modulation in expression levels of these
      components in Arabidopsis or Brassica could be a possible strategy for
      engineering defense against Alternaria blight disease.

PMID- 21947883
TI  - Apolipoprotein A-I mimetic peptide D-4F promotes human endothelial progenitor
      cell proliferation, migration, adhesion though eNOS/NO pathway.
AB  - Circulating endothelial progenitor cells (EPCs) have a critical role in
      endothelial maintenance and repair. Apolipoprotein A-I mimetic peptide D-4F has
      been shown to posses anti-atherogenic properties via sequestration of oxidized
      phospholipids, induction of remodeling of high density lipoprotein and promotion
      of cholesterol efflux from macrophage-derived foam cells. In this study, we test
      the effects of D-4F on EPC biology. EPCs were isolated from the peripheral venous
      blood of healthy male volunteers and characterized by 1,1'-dioctadecyl-3,3,3',3'
      tetramethylindocarbocyanine-labeled acetylated LDL uptake and ulex europaeus
      agglutinin binding and flow cytometry. Cell proliferation, migration, adhesion,
      nitric oxide production and endothelial nitric oxide synthase (eNOS) expression
      in the absence and presence of D-4F or simvastatin (as a positive control), were
      assayed. We demonstrated that D-4F significantly enhanced EPC proliferation,
      migration and adhesion in a dose-dependent manner compared with vehicle. However,
      all of the favorable effects of D-4F on EPCs were dramatically attenuated by
      preincubation with NOS inhibitor L-NAME. Further, D-4F also increased nitric
      oxide production in culture supernatant and the levels of eNOS expression and
      phosphorylation. The stimulatory effects of D-4F (10 MUg/ml) on EPC biology were
      comparable to 0.5 MUM simvastatin. These results suggest that eNOS/NO pathway
      mediates the functional modulation of EPC biology in response to D-4F treatment
      and support the notion that the beneficial role of D-4F on EPCs may be one of the
      important components of its anti-atherogenic potential.

PMID- 21947884
TI  - Structural characterization of plant defensin protein superfamily.
AB  - Plant defensins represent a major innate immune protein superfamily with strong
      inhibitory effects on infectious diseases of humans, antifungal/antibacterial
      activities, proteinase and insect amylase inhibitory activities. They are
      generally defined by their conserved cysteine scaffold with alpha-helix and
      triple strand anti parallel beta-sheet connected to the scaffold. With the genome
      of more plant species being fully sequenced, significant information about newly
      sequenced defensin proteins has been revealed. In this paper, we identify members
      of defensin protein families across plant species and use protein-modeling-based
      structural reconstitution to reveal specific three dimensional hidden features of
      plant defensins mediating defense responses and other interesting biological
      activities in plants. Our data revealed that plant defensins are structurally
      similar to their insect counterparts despite the low amino acid sequence
      similarity between these two organisms. The molecular and structural relationship
      among plant defensins and defensins from other species is discussed.

PMID- 21947885
TI  - Association between cholecystokinin type A receptor haplotypes and growth traits
      in Japanese Hinai-dori crossbred chickens.
AB  - We previously identified quantitative trait loci for body weight and average
      daily gain in a common region between MCW0240 (chr 4: 69.9 Mb) and ABR0622 (chr
      4: 86.3 Mb) on chicken chromosome 4 in an F(2) resource population produced by
      crossing low- and high-growth lines of the Hinai-dori breed. Cholecystokinin type
      A receptor (CCKAR) is a candidate gene affecting growth traits in the region. In
      this study, we genotyped polymorphisms of the CCKAR gene and investigated its
      association with growth traits in a Hinai-dori F(2) intercross population. All
      the exons of the CCKAR gene in the parental population were subjected to PCR
      amplification, nucleotide sequenced and haplotypes identified. To distinguish
      resultant diplotype individuals in the F(2) population, a mismatch amplification
      mutation assay was performed. Five haplotypes (Haplotypes 1-5) were accordingly
      identified. Six genotypes produced by the combination of three haplotypes
      (Haplotype 1, 3, and 4) were examined in order to identify associations between
      CCKAR haplotypes and growth traits. The data indicate that Haplotype 1 was
      superior to Haplotype 3 and 4 in body weight at 10 and 14 weeks of age, average
      daily gain between 4 and 10 weeks, 10 and 14 weeks, and 0 and 14 weeks of age. It
      was concluded that CCKAR is a useful marker of growth traits and could be used to
      develop strategies for improving growth traits in the Hinai-dori breed.

PMID- 21947886
TI  - Effects of isoflurane exposure during pregnancy on postnatal memory and learning
      in offspring rats.
AB  - Emerging evidence has demonstrated that exposure to anesthetics early in life
      caused neurohistopathologic changes and persistent behavioral impairments. In
      this study, a maternal fetal rat model was developed to study the effects of
      isoflurane exposure during pregnancy on postnatal memory and learning in the
      offspring. Pregnant rats at gestational day 14 were either exposed to 1.3%
      isoflurane in a humidified 100% oxygen carrier gas or simply humidified 100%
      oxygen without any inhalational anesthetic for 2 h every day before delivery.
      Four weeks later, spatial learning and memory of the offspring were examined
      using the Morris Water Maze. The expression levels of GAP-43 and NPY in the
      hippocampal CA1 region of the pups were determined by immunohistochemistry and RT
      PCR. Simultaneously, the ultrastructure changes in synapse of the hippocampus
      were also observed by transmission electron microscopy (TEM). Isoflurane exposure
      during pregnancy impaired postnatal spatial memory and learning in the offspring
      as shown by the longer escape latency and the fewer original platform crossings
      in the Morris Water Maze test. The number and optical densities of GAP-43 and NPY
      positive cells, as well as the levels of GAP-43 and NPY mRNA, decreased
      significantly in the hippocampus of isoflurane-exposed pups. Furthermore, TEM
      studies showed remarkable changes in synaptic ultrastructure of hippocampus.
      These results indicate that isoflurane exposure during pregnancy could cause
      postnatal spatial memory and learning impairments in offspring rats, which may be
      partially explained by the down-regulation of GAP-43 and NPY in the hippocampal
      area.

PMID- 21947888
TI  - Brucellosis among smallholder cattle farmers in Zambia: public health
      significance.
AB  - A cross-sectional study was performed in Southern and Lusaka provinces of Zambia
      between March and September 2008 to estimate Brucella seroprevalence in cattle
      kept by smallholder dairy farmers (n = 185). Rose Bengal test (RBT) was used as a
      screening test followed by confirmation with competitive ELISA (c-ELISA). We
      investigated 1,323 cattle, of which 383 had a history of receiving vaccination
      against brucellosis and 36 had a history of abortion. Overall seroprevalence was
      6.0% with areas where vaccination was practiced having low seroprevalence. Age
      was associated with Brucella seropositivity (P = 0.03) unlike cattle breed (P =
      0.21) and sex (P = 0.32). At area level, there was a negative correlation (Corr.
      coeff = -0.74) between percentage of animals with brucellosis vaccination history
      (vaccination coverage) and level of brucellosis; percentage of animals with
      history of abortion (Corr. coeff. = -0.82) and brucellosis vaccination coverage.
      However, a positive correlation existed between brucellosis infection levels with
      percentage of animals having a history of abortion (Corr. coeff. = 0.72). History
      of vaccination against brucellosis was positively associated with a positive
      Brucella result on RBT (P = 0.004) whereby animals with history of vaccination
      against brucellosis were more likely to give a positive RBT test results (OR =
      1.52). However, the results of c-ELISA were independent of history of Brucella
      vaccination (P = 0.149) but was positively associated with history of abortion
      (OR = 4.12). Our results indicate a relatively low Brucella seroprevalence in
      cattle from smallholder dairy farmers and that vaccination was effective in
      reducing cases of Brucella infections and Brucella-related abortions. Human
      exposure to Brucella through milk from smallholder farmers could result through
      milk traded on the informal market since that milk is not processed and there no
      quality and safety controls.

PMID- 21947887
TI  - The renin-angiotensin-aldosterone system in 2011: role in hypertension and
      chronic kidney disease.
AB  - Over the past two decades, considerable advances have been made in our
      understanding of the renin-angiotensin-aldosterone system (RAAS) and its roles in
      various disease states. In this review, we will discuss the current state of
      knowledge of the many components of the RAAS, including new data on prorenin and
      its receptors, and important angiotensin fragments. The roles of these components
      of the RAAS in the pathogenesis of primary hypertension and the progression of
      chronic kidney disease (CKD) will also be highlighted. Given the new
      understanding of the many components and roles of the RAAS, it may be possible to
      develop improved therapies for hypertension and CKD.

PMID- 21947889
TI  - Statistical mechanical approach to secondary processes and structural relaxation
      in glasses and glass formers: a leading model to describe the onset of Johari
      Goldstein processes and their relationship with fully cooperative processes.
AB  - The interrelation of dynamic processes active on separated time-scales in glasses
      and viscous liquids is investigated using a model displaying two time-scale
      bifurcations both between fast and secondary relaxation and between secondary and
      structural relaxation. The study of the dynamics allows for predictions on the
      system relaxation above the temperature of dynamic arrest in the mean-field
      approximation, that are compared with the outcomes of the equations of motion
      directly derived within the Mode Coupling Theory (MCT) for under-cooled viscous
      liquids. By varying the external thermodynamic parameters, a wide range of
      phenomenology can be represented, from a very clear separation of structural and
      secondary peak in the susceptibility loss to excess wing structures.

PMID- 21947890
TI  - Influence of stress and temperature on damping behavior of amorphous
      Pd77.5Cu6.0Si 16.5 below Tg.
AB  - In this work we analyzed the mechanical damping behavior of amorphous
      Pd(77.5)Cu(6.0)Si(16.5) below the glass transition temperature (T(g)) with
      creep/recovery measurements. Here a correlation between temperature stimulation
      and external stress is found in an exponential, multiplicative way. This
      demonstrates that not only is the yield stress of the material influenced by
      temperature variation (mechanical melting) but also the secondary relaxation is
      modified under stress and temperature.

PMID- 21947891
TI  - Heterogeneous diffuse interfaces: a new mechanism for arrested coarsening in
      binary mixtures. Heterogeneous diffuse interfaces.
AB  - We discuss the dynamics of binary fluid mixtures in which surface tension density
      is allowed to become locally negative within the interface, while still
      preserving positivity of the overall surface tension (heterogeneous diffuse
      interface). Numerical simulations of two-dimensional Ginzburg-Landau phase field
      equations implementing such mechanism and including hydrodynamic motion, show
      evidence of dynamically arrested domain coarsening. Under specific conditions on
      the functional form of the surface tension density, dynamical arrest can be
      interpreted in terms of the collective dynamics of metastable, non-linear
      excitations of the density field, named compactons, as they are localized to
      finite-size regions of configuration space and strictly zero elsewhere. Aside
      from compactons, the heterogeneous diffuse interface scenario appears to provide
      a robust mechanism for the interpretation of many aspects of soft-glassy
      behaviour in binary fluid mixtures.

PMID- 21947892
TI  - Relaxation time and viscosity of fused silica glass at room temperature.
AB  - Cases of long-term deformation of fused silica glass at room temperature
      attributed to the action of gravity have been reported. Further experimental
      investigations now provide evidence of time-dependent viscous behavior, with a
      time constant of the order of 10 years. Data relating to a pair of fused silica
      reference plates are presented, showing the overall deformation occurred over the
      years; considerations on the pertaining viscosity with aging are also given. An
      account of the observed relaxation process in terms of the Kelvin-Voigt model for
      linear viscoelasticity is provided.

PMID- 21947893
TI  - Simulated glass-forming polymer melts: glass transition temperature and elastic
      constants of the glassy state.
AB  - By means of molecular-dynamics simulation we study a flexible and a semiflexible
      bead-spring model for a polymer melt on cooling through the glass transition.
      Results for the glass transition temperature T(g) and for the elastic properties
      of the glassy state are presented. We find that T(g) increases with chain length
      N and is for all N larger for the semiflexible model. The N dependence of T(g) is
      compared to experimental results from the literature. Furthermore, we
      characterize the polymer glass below T(g) via its elastic properties, i.e., via
      the Lame coefficients lambda and MU. The Lame coefficients are determined from
      the fluctuation formalism which allows to split lambda and MU into affine (Born
      term) and nonaffine (fluctuation term) contributions. We find that the
      fluctuation term represents a substantial correction to the Born term. Since the
      Born terms for lambda and MU are identical, the fluctuation terms are responsible
      for the different temperature dependence of the Lame coefficients. While lambda
      decreases linearly on approaching T(g) from below, the shear modulus MU displays
      a much stronger decrease near T(g). From the present simulation data it is not
      possible to decide whether MU takes a finite value at T(g), as would be expected
      from mode-coupling theory, or vanishes continuously, as suggested by recent work
      from replica theory.

PMID- 21947894
TI  - Experimental evidence for interplay of dynamic heterogeneity and finite-size
      effect in glassy polymers.
AB  - Despite two decades of extensive research, direct experimental evidence of a
      dynamical length scale determining the glass transition of confined polymers has
      yet to emerge. Using a recently established experimental technique of interface
      micro-rheology we provide evidence of finite-size effect truncating the growth of
      a quantity proportional to a dynamical length scale in confined glassy polymers,
      on cooling towards the glass transition temperature. We show how the interplay of
      variation of polymer film thickness and this temperature-dependent growing
      dynamical length scale determines the glass transition temperature, which in our
      case of 2-3 nm thick films, is reduced significantly as compared to their bulk
      values.

PMID- 21947895
TI  - Effect of nanoparticle dispersion on glass transition in thin films of polymer
      nanocomposites.
AB  - We present spectroscopic ellipsometry measurements on thin films of polymer
      nanocomposites consisting of gold nanoparticles embedded in poly(styrene). The
      temperature dependence of thickness variation is used to estimate the glass
      transition temperature, T(g). In these thin films we find a significant
      dependence of T(g) on the nature of dispersion of the embedded nanoparticles. Our
      work thus highlights the crucial role played by the particle polymer interface
      morphology in determining the glass transition in particular and thermo
      mechanical properties of such nanocomposite films.

PMID- 21947896
TI  - The role of the dynamic crossover temperature and the arrest in glass-forming
      fluids.
AB  - We discuss the role of the dynamic glass-forming fragile-to-strong crossover
      (FSC) in supercooled liquids. In the FSC, significant dynamic changes such as the
      decoupling (the violation of the Stokes-Einstein relation) of homologous
      transport parameters, e.g., the density relaxation time tau and the viscosity
      eta, occur at a characteristic temperature T(c). We study the FSC using a scaling
      law approach. In particular, we use both forms of the mode-coupling theory (MCT):
      the original (ideal) and the extended form, which explicitly describes energy
      hopping processes. We demonstrate that T(c) plays the most important physical
      role in understanding dynamic arrest processes.

PMID- 21947897
TI  - Testing "microscopic" theories of glass-forming liquids.
AB  - We assess the validity of "microscopic" approaches of glass-forming liquids based
      on the sole knowledge of the static pair density correlations. To do so, we apply
      them to a benchmark provided by two liquid models that share very similar static
      pair density correlation functions while displaying distinct temperature
      evolutions of their relaxation times. We find that the approaches are
      unsuccessful in describing the difference in the dynamical behavior of the two
      models. Our study is not exhaustive, and we have not tested the effect of adding
      corrections by including, for instance, three-body density correlations. Yet, our
      results appear strong enough to challenge the claim that the slowdown of
      relaxation in glass-forming liquids, for which it is well established that the
      changes of the static structure factor with temperature are small, can be
      explained by "microscopic" approaches only requiring the static pair density
      correlations as nontrivial input.

PMID- 21947898
TI  - Positron annihilation response and broadband dielectric spectroscopy: salol.
AB  - A phenomenological analysis of the ortho-positronium (o-Ps) annihilation from
      positron annihilation lifetime spectroscopy (PALS) and the dynamics from
      broadband dielectric spectroscopy (BDS) are reported on a small molecular glass
      former of intermediate H-bonding and fragility: salol. The dielectric spectra
      extend over a very broad frequency range of about 2 * 10(-2)-3.5 * 10(11) Hz,
      providing information on the alpha-relaxation, the secondary relaxation giving
      rise to the excess wing, and the shallow high-frequency minimum in the micro- to
      milli-meter wave range. A number of empirical correlations between the o-Ps
      lifetime, tau(3)(T), and the various spectral and relaxation features have been
      observed. Thus, the phenomenological evaluation of the tau(3)(T) dependence of
      the PALS response of the amorphous sample reveals three characteristic PALS
      temperatures: T(g)(PALS), T(b1)(L) = 1.15T(g)(PALS) and T(b2)(L) =
      1.25T(g)(PALS), which are discussed in relation to similar findings for some
      typical small molecular vdW- and H-bonded glass formers. A slighter change of the
      slope at T(b1)(L) appears to be related to the transition from excess wing to the
      primary alpha-process-dominated behavior, with the secondary process dominating
      in the deeply supercooled liquid state below T(b1)(L). The high-temperature
      plateau effect in the tau (3)(T) plot occurs at T(b2)(L) and agrees with the
      characteristic Stickel temperature, T(B)(ST), marking a qualitative change of the
      primary alpha process, but it does not follow the relation T(b2)(L) < T(alpha)
      [tau(3)(T(b2)) < tau(alpha)]. Both effects at T(b1)(L) and T(b2)(L) correlate
      with two crossovers in the spectral shape and related non-exponentiality
      parameter of the structural relaxation, beta (KWW). Finally, the application of
      the two-order parameter (TOP) model to the structural relaxation as represented
      by the primary alpha relaxation times from BDS leads to the characteristic TOP
      temperature, T(m)(c), close to T(b1) from PALS. Within this model the
      phenomenological interpretation is offered based on changes in the probability of
      occurrence of solid-like and liquid-like domains to explain the dynamic as well
      as PALS responses. In summary, all the empirical correlations support further
      very close connections between the PALS response and the dielectric relaxation
      behavior in small molecule glass formers.

PMID- 21947899
TI  - Correlation between dynamical heterogeneities, structure and potential-energy
      distribution in a 2D amorphous solid.
AB  - We investigate the collective properties of particles in a 2D experimental system
      which consists of a bi-disperse mixture of colloidal particles confined at an
      air/water interface. We find a direct correlation between structure and dynamical
      heterogeneities in this system: particles belonging to locally ordered structures
      have lower potential energy and are slower than other particles. In a more
      general way we show that particles with high potential energy are dominating the
      dynamics especially in the alpha-relaxation regime.

PMID- 21947900
TI  - Experimental studies of the jamming behaviour of triblock copolymer solutions and
      triblock copolymer-anionic surfactant mixtures.
AB  - Photon correlation spectroscopy and rheological measurements are performed to
      investigate the microscopic dynamics and mechanical responses of aqueous
      solutions of triblock copolymers and aqueous mixtures of triblock copolymers and
      anionic surfactants. Increasing the concentration of triblock copolymers results
      in a sharp increase in the magnitude of the complex moduli characterising the
      samples. This is understood in terms of the changes in the aggregation and
      packing behaviours of the copolymers and the constraints imposed upon their
      dynamics due to increased close packing. The addition of suitable quantities of
      an anionic surfactant to a strongly elastic copolymer solution results in a
      decrease in the complex moduli of the samples by several decades. It is argued
      that the shape anisotropy and size polydispersity of the micelles comprising
      mixtures cause dramatic changes in the packing behaviour, resulting in sample
      unjamming and the observed decrease in complex moduli. Finally, a phase diagram
      is constructed in the temperature-surfactant concentration plane to summarise the
      jamming-unjamming behaviour of aggregates constituting triblock copolymer-anionic
      surfactant mixtures.

PMID- 21947901
TI  - On the potential energy landscape of supercooled liquids and glasses.
AB  - The activation-relaxation technique (ART), a saddle-point search method, is
      applied to determine the potential energy landscape around supercooled and glassy
      configurations of a three-dimensional binary Lennard-Jones system. We show a
      strong relation between the distribution of activation energies around a given
      glassy configuration and its history, in particular, the cooling rate used to
      produce the glass and whether or not the glass was plastically deformed prior to
      sampling. We also compare the thermally activated transitions found by ART around
      a supercooled configuration with the succession of transitions undergone by the
      same supercooled liquid during a time trajectory simulated by molecular dynamics.
      We find that ART is biased towards more heterogeneous transitions with higher
      activation energies and more broken bonds than the MD simulation.

PMID- 21947902
TI  - Field theory of fluctuations in glasses.
AB  - We develop a field-theoretical description of dynamical heterogeneities and
      fluctuations in supercooled liquids close to the (avoided) MCT singularity. Using
      quasi-equilibrium arguments, we eliminate time from the description and we
      completely characterize fluctuations in the beta regime. We identify different
      sources of fluctuations and show that the most relevant ones are associated to
      variations of "self-induced disorder" in the initial condition of the dynamics.
      It follows that heterogeneites can be described through a cubic field theory with
      an effective random field term. The phenomenon of perturbative dimensional
      reduction ensues, well known in random field problems, which implies an upper
      critical dimension of the theory equal to 8. We apply our theory to finite size
      scaling for mean-field systems and we test its prediction against numerical
      simulations.

PMID- 21947903
TI  - Small area estimates reveal high cigarette smoking prevalence in low-income
      cities of Los Angeles county.
AB  - Los Angeles County has among the lowest smoking rates of large urban counties in
      the USA. Nevertheless, concerning disparities persist as high smoking prevalence
      is found among certain subgroups. We calculated adult smoking prevalence in the
      incorporated cities of Los Angeles County in order to identify cities with high
      smoking prevalence. The prevalence was estimated by a model-based small area
      estimation method with utilization of three data sources, including the 2007 Los
      Angeles County Health Survey, the 2000 Census, and the 2007 Los Angeles County
      Population Estimates and Projection System. Smoking prevalence varied
      considerably across cities, with a more than fourfold difference between the
      lowest (5.3%) and the highest prevalence (21.7%). Higher smoking prevalence was
      generally found in socioeconomically disadvantaged cities. The disparities
      identified here add another layer of data to our knowledge of the health
      inequities experienced by low-income urban communities and provide much sought
      data for local tobacco control. Our study also demonstrates the feasibility of
      providing credible local estimates of smoking prevalence using the model-based
      small area estimation method.

PMID- 21947904
TI  - A swarm optimized neural network system for classification of microcalcification
      in mammograms.
AB  - Early detection of microcalcification clusters in breast tissue will
      significantly increase the survival rate of the patients. Radiologists use
      mammography for breast cancer diagnosis at early stage. It is a very challenging
      and difficult task for radiologists to correctly classify the abnormal regions in
      the breast tissue, because mammograms are noisy images. To improve the accuracy
      rate of detection of breast cancer, a novel intelligent computer aided classifier
      is used, which detects the presence of microcalcification clusters. In this
      paper, an innovative approach for detection of microcalcification in digital
      mammograms using Swarm Optimization Neural Network (SONN) is used. Prior to
      classification Laws texture features are extracted from the image to capture
      descriptive texture information. These features are used to extract texture
      energy measures from the Region of Interest (ROI) containing microcalcification
      (MC). A feedforward neural network is used for detection of abnormal regions in
      breast tissue is optimally designed using Particle Swarm Optimization algorithm.
      The proposed intelligent classifier is evaluated based on the MIAS database where
      51 malignant, 63 benign and 208 normal images are utilized. The approach has also
      been tested on 216 real time clinical images having abnormalities which showed
      that the results are statistically significant. With the proposed methodology,
      the area under the ROC curve (A ( z )) reached 0.9761 for MIAS database and
      0.9138 for real clinical images. The classification results prove that the
      proposed swarm optimally tuned neural network highly contribute to computer-aided
      diagnosis of breast cancer.

PMID- 21947905
TI  - A rare allergy to a polyether dental impression material.
AB  - Polyether impression materials have been used in dentistry for more than 40
      years. Allergic reactions to these materials such as reported in the 1970s ceased
      after replacement of a catalyst. Very recently, however, patients have started to
      report symptoms that suggest a new allergic reaction from polyether impression
      materials. Here, we report on the results of allergy testing with polyether
      impression materials as well as with its components. Eight patients with clinical
      symptoms of a contact allergy (swelling, redness or blisters) after exposure to a
      polyether impression material were subjected to patch tests, two of them
      additionally to a prick test. A further patient with atypical symptoms of an
      allergy (nausea and vomiting after contact with a polyether impression material
      in the oral cavity) but with a history of other allergic reaction was also patch
      tested. The prick tests showed no immediate reactions in the two patients tested.
      In the patch tests, all eight patients with typical clinical symptoms showed
      positive reactions to the mixed polyether impression materials, to the base paste
      or to a base paste component. The patient with the atypical clinical symptoms did
      not show any positive patch test reactions. Polyether impression materials may
      evoke type IV allergic reactions. The causative agent was a component of the base
      paste. In consideration of the widespread use of this impression material
      (millions of applications per year) and in comparison to the number of adverse
      reactions from other dental materials, the number of such allergic reactions is
      very low. In very scarce cases, positive allergic reactions to polyether
      impression materials are possible.

PMID- 21947907
TI  - A standardized guideline-based algorithm coupled with online decision-making
      tool: the new frontier for efficient management of syncope?

PMID- 21947906
TI  - Microleakage of silorane- and methacrylate-based class V composite restorations.
AB  - The marginal integrity of class V restorations in a silorane- and a group of
      methacrylate-based composite resins with varying viscosities was tested in the
      present study. Different adhesives (OptiBond FL, KerrHawe; AdheSE One, Vivadent;
      or Silorane System Adhesive, 3M ESPE) were applied to 168 standardized class V
      cavities. The cavities (n = 12) were filled with a wide range of different
      viscous composite resins: Filtek Silorane, 3M ESPE; els and els flow, Saremco;
      Tetric EvoCeram and Tetric EvoFlow, Vivadent; Grandio, Voco; and Ultraseal XT
      Plus, Ultradent. Microleakage of the restoration was assessed by dye penetration
      (silver staining) on multiple sections with and without thermocycling and
      mechanical loading (TCML: 5,000 * 5-55 degrees C; 30 s/cycle; 500,000 * 72.5 N,
      1.6 Hz). Data were statistically analyzed with the Mann-Whitney U test and the
      Error Rates Method (ERM). The silorane-based composite resin yielded the lowest
      dye penetration after TCML. Microleakage of methacrylate-based composite
      restorations, in general (ERM), was statistically significantly influenced by the
      adhesive system, Moreover, dye penetration at enamel margins was significantly
      lower than dye penetration at dentin margins. The chemical basis of composite
      resins and adjacent tooth substance seems to strongly influence marginal sealing
      of class V restorations for methacrylate-based materials. Moreover, the steps of
      dental adhesives used affected marginal integrity. The silorane-based composite
      resin evaluated in the present study exhibits the best marginal seal. The three
      step adhesive yielded better marginal sealing than the one-step adhesive for
      methacrylate-based class V composite restorations.

PMID- 21947910
TI  - Special issue as a tribute to Lewis E Kay on his 50th birthday.

PMID- 21947908
TI  - Cytokine inhibition and time-related influence of inflammatory stimuli on the
      hyperalgesia induced by the nucleus pulposus.
AB  - INTRODUCTION: The symptoms of lumbar disc herniation, such as low back pain and
      sciatica, have been associated with local release of cytokines following the
      inflammatory process induced by the contact of the nucleus pulposus (NP) with the
      spinal nerve. MATERIAL AND METHODS: Using an animal experimental model of
      intervertebral disc herniation and behavioral tests to evaluate mechanical
      (electronic von Frey test) and thermal (Hargreaves Plantar test) hyperalgesia in
      the hind paw of rats submitted to the surgical model, this study aimed to detect
      in normal intervertebral disc the cytokines known to be involved in the
      mechanisms of inflammatory hyperalgesia, to observe if previous exposure of the
      intervertebral disc tissue to specific antibodies could affect the pain behavior
      (mechanical and thermal hyperalgesia) induced by the NP, and to observe the
      influence of the time of contact of the NP with the fifth lumbar dorsal root
      ganglion (L5-DRG) in the mechanical and thermal hyperalgesia. RESULTS: The
      cytokines present at highest concentrations in the rat NP were TNF-alpha, IL
      1beta and CINC-1. Rats submitted to the disc herniation experimental model, in
      which a NP from the sacrococcygeal region is deposited over the right L5-DRG,
      showed increased mechanical and thermal hyperalgesia that lasted at least 7
      weeks. When the autologous NP was treated with antibodies against the three
      cytokines found at highest concentrations in the NP (TNF-alpha, IL-1beta and CINC
      1), there was decrease in both mechanical and thermal hyperalgesia in different
      time points, suggesting that each cytokine may be important for the hyperalgesia
      in different steps of the inflammatory process. The surgical remotion of the NP
      from herniated rats 1 week after the implantation reduced the hyperalgesia to the
      level similar to the control group. This reduction in the hyperalgesia was also
      observed in the group that had the NP removed 3 weeks after the implantation,
      although the intensity of the hyperalgesia did not decreased totally. The removal
      of the NP after 5 weeks did not changed the hyperalgesia observed in the hind
      paw, which suggests that the longer the contact of the NP with the DRG, the
      greater is the possibility of development of chronic pain. CONCLUSION: Together
      our results indicate that specific cytokines released during the inflammatory
      process induced by the herniated intervertebral disc play fundamental role in the
      development of the two modalities of hyperalgesia (mechanical and thermal) and
      that the maintenance of this inflammation may be the most important point for the
      chronification of the pain.

PMID- 21947911
TI  - Dissecting electrostatic interactions in Bacillus circulans xylanase through NMR
      monitored pH titrations.
AB  - NMR-monitored pH titration curves of proteins provide a rich source of structural
      and electrostatic information. Although relatively straightforward to measure,
      interpreting pH-dependent chemical shift changes to obtain site-specific acid
      dissociation constants (pK (A) values) is challenging. In order to analyze the
      biphasic titrations exhibited by the side chain (13)C(gamma) nuclei of the
      nucleophilic Glu78 and general acid/base Glu172 in Bacillus circulans xylanase,
      we have revisited the formalism for the ionization equilibria of two coupled
      acidic residues. In general, fitting NMR-monitored pH titration curves for such a
      system will only yield the two macroscopic pK (A) values that reflect the
      combined effects of both deprotonation reactions. However, through the use of
      mutations complemented with ionic strength-dependent measurements, we are able to
      extract the four microscopic pK (Ai) values governing the branched acid/base
      equilibria of Glu78 and Glu172 in BcX. These data, confirmed through theoretical
      calculations, help explain the pH-dependent mechanism of this model GH11 xylanase
      by demonstrating that the kinetically determined pK (A) values and hence
      catalytic roles of these two residues result from their electrostatic coupling.

PMID- 21947912
TI  - Complete determination of the Pin1 catalytic domain thermodynamic cycle by NMR
      lineshape analysis.
AB  - The phosphorylation-specific peptidyl-prolyl isomerase Pin1 catalyzes the
      isomerization of the peptide bond preceding a proline residue between cis and
      trans isomers. To best understand the mechanisms of Pin1 regulation, rigorous
      enzymatic assays of isomerization are required. However, most measures of
      isomerase activity require significant constraints on substrate sequence and only
      yield rate constants for the cis isomer, [Formula: see text] and apparent
      Michaelis constants, [Formula: see text]. By contrast, NMR lineshape analysis is
      a powerful tool for determining microscopic rates and populations of each state
      in a complex binding scheme. The isolated catalytic domain of Pin1 was employed
      as a first step towards elucidating the reaction scheme of the full-length
      enzyme. A 24-residue phosphopeptide derived from the amyloid precurser protein
      intracellular domain (AICD) phosphorylated at Thr668 served as a biologically
      relevant Pin1 substrate. Specific (13)C labeling at the Pin1-targeted proline
      residue provided multiple reporters sensitive to individual isomer binding and on
      enzyme catalysis. We have performed titration experiments and employed lineshape
      analysis of phosphopeptide (13)C-(1)H constant time HSQC spectra to determine
      [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see
      text] for the catalytic domain of Pin1 acting on this AICD substrate. The on
      enzyme equilibrium value of [E.trans]/[E.cis] = 3.9 suggests that the catalytic
      domain of Pin1 is optimized to operate on this substrate near equilibrium in the
      cellular context. This highlights the power of lineshape analysis for determining
      the microscopic parameters of enzyme catalysis, and demonstrates the feasibility
      of future studies of Pin1-PPIase mutants to gain insights on the catalytic
      mechanism of this important enzyme.

PMID- 21947913
TI  - Mathematical treatment of adiabatic fast passage pulses for the computation of
      nuclear spin relaxation rates in proteins with conformational exchange.
AB  - Although originally designed for broadband inversion and decoupling in NMR
      spectroscopy, recent methodological developments have introduced adiabatic fast
      passage (AFP) pulses into the field of protein dynamics. AFP pulses employ a
      frequency sweep, and have not only superior inversion properties with respect to
      offset effects, but they are also easily implemented into a pulse sequence. As
      magnetization is dragged from the +z to the -z direction, Larmor precession is
      impeded since magnetization becomes spin-locked, which is a potentially useful
      feature for the investigation of microsecond to millisecond dynamics. A major
      drawback of these pulses as theoretical prediction is concerned, however, results
      from their time-dependent offset: simulations of spin density matrices under the
      influence of a time-dependent Hamiltonian with non-commuting elements are costly
      in terms of computational time, rendering data analysis impracticable. In this
      paper we suggest several ways to reduce the computational time without
      compromising accuracy with respect to effects such as cross-correlated relaxation
      and modulation of the chemical shift.

PMID- 21947914
TI  - The structure and dynamic properties of the complete histidine phosphotransfer
      domain of the chemotaxis specific histidine autokinase CheA from Thermotoga
      maritima.
AB  - The bacterial histidine autokinase CheA contains a histidine phosphotransfer
      (Hpt) domain that accepts a phosphate from the catalytic domain and donates the
      phosphate to either target response regulator protein, CheY or CheB. The Hpt
      domain forms a helix-bundle structure with a conserved four-helix bundle motif
      and a variable fifth helix. Observation of two nearly equally populated
      conformations in the crystal structure of a Hpt domain fragment of CheA from
      Thermotoga maritima containing only the first four helices suggests more mobility
      in a tightly packed helix bundle structure than previously thought. In order to
      examine how the structures of Hpt domain homologs may differ from each other
      particularly in the conformation of the last helix, and whether an alternative
      conformation exists in the intact Hpt domain in solution, we have solved a high
      resolution, solution structure of the CheA Hpt from T. maritima and characterized
      the backbone dynamics of this protein. The structure contains a four-helix bundle
      characteristic of histidine phosphotransfer domains. The position and orientation
      of the fifth helix resembles those in known Hpt domain crystal and solution
      structures in other histidine kinases. The alternative conformation that was
      reported in the crystal structure of the CheA Hpt from T. maritima missing the
      fifth helix is not detected in the solution structure, suggesting a role for the
      fifth helix in providing stabilizing forces to the overall structure.

PMID- 21947916
TI  - Active site dynamics in NADH oxidase from Thermus thermophilus studied by NMR
      spin relaxation.
AB  - We have characterized the backbone dynamics of NADH oxidase from Thermus
      thermophilus (NOX) using a recently-developed suite of NMR experiments designed
      to isolate exchange broadening, together with (15)N R (1), R (1rho ), and {(1)H}
      (15)N steady-state NOE relaxation measurements performed at 11.7 and 18.8 T. NOX
      is a 54 kDa homodimeric enzyme that belongs to a family of structurally
      homologous flavin reductases and nitroreductases with many potential
      biotechnology applications. Prior studies have suggested that flexibility is
      involved in the catalytic mechanism of the enzyme. The active site residue W47
      was previously identified as being particularly important, as its level of
      solvent exposure correlates with enzyme activity, and it was observed to undergo
      "gating" motions in computer simulations. The NMR data are consistent with these
      findings. Signals from W47 are dynamically broadened beyond detection and several
      other residues in the active site have significant R ( ex ) contributions to
      transverse relaxation rates. In addition, the backbone of S193, whose side chain
      hydroxyl proton hydrogen bonds directly with the FMN cofactor, exhibits extensive
      mobility on the ns-ps timescale. We hypothesize that these motions may facilitate
      structural rearrangements of the active site that allow NOX to accept both FMN
      and FAD as cofactors.

PMID- 21947915
TI  - The feasibility of parameterizing four-state equilibria using relaxation
      dispersion measurements.
AB  - Coupled equilibria play important roles in controlling information flow in
      biochemical systems, including allosteric molecules and multidomain proteins. In
      the simplest case, two equilibria are coupled to produce four interconverting
      states. In this study, we assessed the feasibility of determining the degree of
      coupling between two equilibria in a four-state system via relaxation dispersion
      measurements. A major bottleneck in this effort is the lack of efficient
      approaches to data analysis. To this end, we designed a strategy to efficiently
      evaluate the smoothness of the target function surface (TFS). Using this
      approach, we found that the TFS is very rough when fitting benchmark CPMG data to
      all adjustable variables of the four-state equilibria. After constraining a
      portion of the adjustable variables, which can often be achieved through
      independent biochemical manipulation of the system, the smoothness of TFS
      improves dramatically, although it is still insufficient to pinpoint the
      solution. The four-state equilibria can be finally solved with further
      incorporation of independent chemical shift information that is readily
      available. We also used Monte Carlo simulations to evaluate how well each
      adjustable parameter can be determined in a large kinetic and thermodynamic
      parameter space and how much improvement can be achieved in defining the
      parameters through additional measurements. The results show that in favorable
      conditions the combination of relaxation dispersion and biochemical manipulation
      allow the four-state equilibrium to be parameterized, and thus coupling strength
      between two processes to be determined.

PMID- 21947917
TI  - Siderocalin Q83 exhibits differential slow dynamics upon ligand binding.
AB  - Siderocalin Q83 is a small soluble protein that has the ability to bind two
      different ligands (enterobactin and arachidonic acid) simultaneously in two
      distinct binding sites. Here we report that Q83 exhibits an intriguing dynamic
      behavior. In its free form, the protein undergoes significant micro-to
      millisecond dynamics. When binding arachidonic acid, the motions of the
      arachidonic acid binding site are quenched while the dynamics at the enterobactin
      binding site increases. Reciprocally, enterobactin binding to Q83 quenches the
      motions at the enterobactin binding site and increases the slow dynamics at the
      arachidonic acid binding site. Additionally, in the enterobactin-bound state, the
      excited state of the arachidonic acid binding site resembles the arachidonic acid
      bound state. These observations strongly suggest an allosteric regulation where
      binding of one ligand enhances the affinity of Q83 for the other one.
      Additionally, our data strengthen the emerging view of proteins as dynamic
      ensembles interconverting between different sub-states with distinct
      functionalities.

PMID- 21947918
TI  - Measurement of (1)H-(15)N and (1)H-(13)C residual dipolar couplings in nucleic
      acids from TROSY intensities.
AB  - Analogous to the recently introduced ARTSY method for measurement of one-bond
      (1)H-(15)N residual dipolar couplings (RDCs) in large perdeuterated proteins, we
      introduce methods for measurement of base (13)C-(1)H and (15)N-(1)H RDCs in
      protonated nucleic acids. Measurements are based on quantitative analysis of
      intensities in (1)H-(15)N and (13)C-(1)H TROSY-HSQC spectra, and are illustrated
      for a 71-nucleotide adenine riboswitch. Results compare favorably with those of
      conventional frequency-based measurements in terms of completeness and
      convenience of use. The ARTSY method derives the size of the coupling from the
      ratio of intensities observed in two TROSY-HSQC spectra recorded with different
      dephasing delays, thereby minimizing potential resonance overlap problems.
      Precision of the RDC measurements is limited by the signal-to-noise ratio, S/N,
      achievable in the 2D TROSY-HSQC reference spectrum, and is approximately given by
      30/(S/N) Hz for (15)N-(1)H and 65/(S/N) Hz for (13)C-(1)H. The signal-to-noise
      ratio of both (1)H-(15)N and (1)H-(13)C spectra greatly benefits when water
      magnetization during the experiments is not perturbed, such that rapid
      magnetization transfer from bulk water to the nucleic acid, mediated by rapid
      amino and hydroxyl hydrogen exchange coupled with (1)H-(1)H NOE transfer, allows
      for fast repetition of the experiment. RDCs in the mutated helix 1 of the
      riboswitch are compatible with nucleotide-specifically modeled, idealized A-form
      geometry and a static orientation relative to the helix 2/3 pair, which differs
      by ca 6 degrees  relative to the X-ray structure of the native riboswitch.

PMID- 21947919
TI  - A rigid disulfide-linked nitroxide side chain simplifies the quantitative
      analysis of PRE data.
AB  - The measurement of (1)H transverse paramagnetic relaxation enhancement (PRE) has
      been used in biomolecular systems to determine long-range distance restraints and
      to visualize sparsely-populated transient states. The intrinsic flexibility of
      most nitroxide and metal-chelating paramagnetic spin-labels, however, complicates
      the quantitative interpretation of PREs due to delocalization of the paramagnetic
      center. Here, we present a novel, disulfide-linked nitroxide spin label, R1p, as
      an alternative to these flexible labels for PRE studies. When introduced at
      solvent-exposed alpha-helical positions in two model proteins, calmodulin (CaM)
      and T4 lysozyme (T4L), EPR measurements show that the R1p side chain exhibits
      dramatically reduced internal motion compared to the commonly used R1 spin label
      (generated by reacting cysteine with the spin labeling compound often referred to
      as MTSL). Further, only a single nitroxide position is necessary to account for
      the PREs arising from CaM S17R1p, while an ensemble comprising multiple
      conformations is necessary for those observed for CaM S17R1. Together, these
      observations suggest that the nitroxide adopts a single, fixed position when R1p
      is placed at solvent-exposed alpha-helical positions, greatly simplifying the
      interpretation of PRE data by removing the need to account for the intrinsic
      flexibility of the spin label.

PMID- 21947920
TI  - Visualizing the principal component of 1H, 15N-HSQC NMR spectral changes that
      reflect protein structural or functional properties: application to troponin C.
AB  - Laboratories often repeatedly determine the structure of a given protein under a
      variety of conditions, mutations, modifications, or in a number of states. This
      approach can be cumbersome and tedious. Given then a database of structures,
      identifiers, and corresponding (1)H,(15)N-HSQC NMR spectra for homologous
      proteins, we investigated whether structural information could be ascertained for
      a new homolog solely from its (1)H,(15)N-HSQC NMR spectrum. We addressed this
      question with two different approaches. First, we used a semi-automated approach
      with the program, ORBplus. ORBplus looks for patterns in the chemical shifts and
      correlates these commonalities to the explicit property of interest. ORBplus
      ranks resonances based on consistency of the magnitude and direction of the
      chemical shifts within the database, and the chemical shift correlation of the
      unknown protein with the database. ORBplus visualizes the results by a histogram
      and a vector diagram, and provides residue specific predictions on structural
      similarities with the database. The second method we used was partial least
      squares (PLS), which is a multivariate statistical technique used to correlate
      response and predictor variables. We investigated the ability of these methods to
      predict the tertiary structure of the contractile regulatory protein troponin C.
      Troponin C undergoes a closed-to-open conformational change, which is coupled to
      its function in muscle. We found that both ORBplus and PLS were able to identify
      patterns in the (1)H,(15)N-HSQC NMR data from different states of troponin C that
      correlated to its conformation.

PMID- 21947921
TI  - Longitudinal exchange: an alternative strategy towards quantification of dynamics
      parameters in ZZ exchange spectroscopy.
AB  - Longitudinal exchange experiments facilitate the quantification of the rates of
      interconversion between the exchanging species, along with their longitudinal
      relaxation rates, by analyzing the time-dependence of direct correlation and
      exchange cross peaks. Here we present a simple and robust alternative to this
      strategy, which is based on the combination of two complementary experiments, one
      with and one without resolving exchange cross peaks. We show that by combining
      the two data sets systematic errors that are caused by differential line
      broadening of the exchanging species are avoided and reliable quantification of
      kinetic and relaxation parameters in the presence of additional conformational
      exchange on the ms-MUs time scale is possible. The strategy is applied to a
      bistable DNA oligomer that displays different line-broadening in the two
      exchanging species.

PMID- 21947923
TI  - Measurement of amide hydrogen exchange rates with the use of radiation damping.
AB  - A simple method for measuring amide hydrogen exchange rates is presented, which
      is based on the selective inversion of water magnetization with the use of
      radiation damping. Simulations show that accurate exchange rates can be measured
      despite the complications of radiation damping and cross relaxation to the
      exchange process between amide and water protons. This method cannot eliminate
      the contributions of the exchange-relayed NOE and direct NOE to the measured
      exchange rates, but minimize the direct NOE contribution. In addition, the amides
      with a significant amount of such indirect contributions are possible to be
      identified from the shape of the exchange peak intensity profiles or/and from the
      apparent relaxation rates of amide protons which are extracted from fitting the
      intensity profiles to an equation established here for our experiment. The method
      was tested on ubiquitin and also applied to an acyl carrier protein. The amide
      exchange rates for the acyl carrier protein at two pHs indicate that the entire
      protein is highly dynamic on the second timescale. Low protection factors for the
      residues in the regular secondary structural elements also suggest the presence
      of invisible unfolded species. The highly dynamic nature of the acyl carrier
      protein may be crucial for its interactions with its substrate and enzymes.

PMID- 21947922
TI  - Domain cooperativity in multidomain proteins: what can we learn from molecular
      alignment in anisotropic media?
AB  - Many proteins have modular design with multiple globular domains connected via
      flexible linkers. As a simple model of such system, we study a tandem construct
      consisting of two identical SH3 domains and a variable-length Gly/Ser linker.
      When the linker is short, this construct represents a dumbbell-shaped molecule
      with limited amount of domain-domain mobility. Due to its elongated shape, this
      molecule efficiently aligns in steric alignment media. As the length of the
      linker increases, the two domains become effectively uncoupled and begin to
      behave as independent entities. Consequently, their degree of alignment drops,
      approaching that found in the (near-spherical) isolated SH3 domains. To model the
      dependence of alignment parameters on the length of the interdomain linker, we
      have generated in silico a series of conformational ensembles representing SH3
      tandems with different linker length. These ensembles were subsequently used as
      input for alignment prediction software PALES. The predicted alignment tensors
      were compared with the results of experimental measurements using a series of
      tandem-SH3 samples in PEG/hexanol alignment media. This comparison broadly
      confirmed the expected trends. At the same time, it has been found that the
      isolated SH3 domain aligns much stronger than expected. This finding can be
      attributed to complex morphology of the PEG/hexanol media and/or to weak site
      specific interactions between the protein and the media. In the latter case,
      there are strong indications that electrostatic interactions may play a role. The
      fact that PEG/hexanol does not behave as a simple steric media should serve as a
      caution for studies that use PALES as a quantitative prediction tool (especially
      for disordered proteins). Further progress in this area depends on our ability to
      accurately model the anisotropic media and its site-specific interactions with
      protein molecules. Once this ability is improved, it should be possible to use
      the alignment parameters as a measure of domain-domain cooperativity, thus
      identifying the situations where two domains transiently interact with each other
      or become coupled through a partially structured linker.

PMID- 21947924
TI  - NMR detection and characterization of sialylated glycoproteins and cell surface
      polysaccharides.
AB  - Few solution NMR pulse sequences exist that are explicitly designed to
      characterize carbohydrates (glycans). This is despite the essential role
      carbohydrate motifs play in cell-cell communication, microbial pathogenesis,
      autoimmune disease progression and cancer metastasis, and despite that fact that
      glycans, often shed to extra-cellular fluids, can be diagnostic of disease. Here
      we present a suite of two dimensional coherence experiments to measure three
      different correlations (H3-C2, H3-C1, and C1-C2) on sialic acids, a group of nine
      carbon carbohydrates found on eukaryotic cell surfaces that often play a key role
      in disease processes. The chemical shifts of the H3, C2, and C1 nuclei of sialic
      acids are sensitive to carbohydrate linkage, linkage conformation, and ionization
      state of the C1 carboxylate. The experiments reported include rigorous filter
      elements to enable detection and characterization of isotopically labeled sialic
      acids with high sensitivity in living cells and crude isolates with minimal
      interference from unwanted signals arising from the ~1% (13)C-natural abundance
      of cellular metabolites. Application is illustrated with detection of sialic
      acids on living cells, in unpurified mixtures, and at the terminus of the N
      glycan on the 55 kDa immunoglobulin G Fc.

PMID- 21947925
TI  - Topology and immersion depth of an integral membrane protein by paramagnetic
      rates from dissolved oxygen.
AB  - In studies of membrane proteins, knowledge of protein topology can provide useful
      insight into both structure and function. In this work, we present a solution NMR
      method for the measurement the tilt angle and average immersion depth of alpha
      helices in membrane proteins, from analysis of the paramagnetic relaxation rate
      enhancements arising from dissolved oxygen. No modification to the micelle or
      protein is necessary, and the topology of both transmembrane and amphipathic
      helices are readily determined. We apply this method to the measure the topology
      of a monomeric mutant of phospholamban (AFA-PLN), a 52-residue membrane protein
      containing both an amphipathic and a transmembrane alpha helix. In
      dodecylphosphocholine micelles, the amphipathic helix of AFA-PLN was found to
      have a tilt angle of 87 degrees  +/- 1 degrees  and an average immersion depth of
      13.2 A. The transmembrane helix was found to have an average immersion depth of
      5.4 A, indicating residues 41 and 42 are closest to the micelle centre. The
      resolution of paramagnetic relaxation rate enhancements from dissolved oxygen
      compares favourably to those from Ni (II), a hydrophilic paramagnetic species.

PMID- 21947926
TI  - Zn-binding AZUL domain of human ubiquitin protein ligase Ube3A.
AB  - Ube3A (also referred to as E6AP for E6 Associated Protein) is a E3 ubiquitin
      protein ligase implicated in the development of Angelman syndrome by controlling
      degradation of synaptic protein Arc and oncogenic papilloma virus infection by
      controlling degradation of p53. This article describe the solution NMR structure
      of the conserved N-terminal domain of human Ube3A (residues 24-87) that contains
      two residues (Cys44 and Arg62) found  to be mutated in patients with Angelman
      syndrome. The structure of this domain  adopts a novel Zn-binding  fold we called
      AZUL (Amino-terminal Zn-finger of Ube3a Ligase). The AZUL  domain has a helix
      loop-helix architecture with a Zn ion coordinated by four Cys residues arranged
      in Cys-X(4)-Cys-X(4)-Cys-X(28)-Cys motif. Three of the Zn-bound residues are
      located in a 23-residue long and well structured loop that connects two alpha
      helicies.

PMID- 21947927
TI  - Simultaneous measurement of 1H-15N and methyl 1Hm-13Cm residual dipolar couplings
      in large proteins.
AB  - A two-dimensional TROSY-based SIM-(13)C(m)-(1)H(m)/(1)H-(15)N NMR experiment for
      simultaneous measurements of methyl (1) D (CH) and backbone amide (1) D (NH)
      residual dipolar couplings (RDC) in {U-[(15)N,(2)H]; Iledelta1-[(13)CH(3)];
      Leu,Val-[(13)CH(3)/(12)CD(3)]}-labeled samples of large proteins is described.
      Significant variation in the alignment tensor of the 82-kDa enzyme Malate
      synthase G is observed as a function of only slight changes in experimental
      conditions. The SIM-(13)C(m)-(1)H(m)/(1)H-(15)N data sets provide convenient
      means of establishing the alignment tensor characteristics via the measurement of
      (1) D (NH) RDCs in the same protein sample.

PMID- 21947928
TI  - Origin and removal of mixed-phase artifacts in gradient sensitivity enhanced
      heteronuclear single quantum correlation spectra.
AB  - Here we describe phasing anomalies observed in gradient sensitivity enhanced
      (15)N-(1)H HSQC spectra, and analyze their origin. It is shown that, as a result
      of (15)N off-resonance effects, dispersive contributions to the (1)H signal
      become detectable, and lead to (15)N-offset dependent phase errors. Strategies
      that effectively suppress these artifacts are presented.

PMID- 21947929
TI  - Variation of heavy metal and micro and macro element concentrations of bread and
      durum wheats and their relationship in grain of Turkish wheat cultivars.
AB  - The 64 varieties displayed a large variation for all mineral elements,
      investigated Fe, Mn and Zn, ranging from 24.2 to 43.1 mg/kg, 27.6 to 64.8 mg/kg
      and 10.4 to 38.2 mg/kg, respectively. The mean Ca, K, Mg, Na, P and S
      concentrations in wheat rain varieties amounted to 378, 4,266, 1,183, 317, 3,513
      and 1,542 mg/kg, respectively. Ca, K, Mg, Na, P and S contents of wheat varieties
      changed at the levels between 266 and 531 mg/kg, 3,029 and 5,566 mg/kg, 972 and
      1,525 mg/kg, 277 and 368 mg/kg, 2,422 and 4,610 mg/kg and 1,241 to 2,052 mg/kg,
      respectively. The concentrations of Al, Cu, Fe, Mn and Zn of durum wheat samples
      were found at high levels. The mean Al, Cr, Mo, Ni, Cu, Fe, Mn and Zn
      concentrations in durum wheat varieties amounted to 10.93, 0.47, 0.72, 0.72,
      5.37, 34.9, 37.28 and 20.88 mg/kg, respectively.

PMID- 21947930
TI  - Extensive herpes zoster involvement following mycophenolate mofetil therapy for
      sarcoidosis.

PMID- 21947931
TI  - Expression of apoptosis-related proteins and its clinical implication in
      surgically resected gastric carcinoma.
AB  - Apoptosis, via caspase cascade, is involved in tumorigenesis and progression, and
      thus, altered apoptosis-related protein expressions have clinical and prognostic
      significance. Moreover, the apoptosis pathway is highlighted due to the recent
      introduction of apoptosis-targeted therapy for several genes such as the X-linked
      inhibitor of apoptosis protein (XIAP). XIAP is the most potent direct inhibitor
      of caspase, and XIAP-associated factor 1 (XAF1) and secondary mitochondrial
      activator of caspase/direct IAP-binding protein with low PI (Smac/DIABLO) are
      negative regulators of XIAP. In this study, we evaluated the expression of these
      proteins and investigated their clinical and prognostic significance in gastric
      carcinomas. Immunohistochemical analysis by using the tissue array method was
      performed for XIAP, survivin, Bcl-2, XAF1, Smac/DIABLO, and cleaved caspase-3
      proteins in 1,162 surgically resected gastric carcinoma cases. XIAP expression
      was related to the advanced stage. The expression of XIAP showed negative
      relationship with XAF1 and Smac/DIABLO expressions. In addition, XIAP expression
      was associated with a poor prognosis and was also proved to be an independent
      prognostic factor. Cleaved caspase-3 expression was related to the early stage.
      In addition, cleaved caspase-3 expression was associated with a favorable
      prognosis and was also proved to be an independent prognostic factor. The
      expression of XIAP showed an inverse relationship with cleaved caspase-3. In
      addition, the expression of XAF1 and Smac/DIABLO had a positive relationship with
      cleaved caspase-3. These findings are consistent with their known functions, and
      they may help to identify individuals best suited for apoptosis-targeted therapy
      as a baseline data in gastric carcinoma.

PMID- 21947932
TI  - Evolving knowledge about age and hypothermic circulatory arrest in aortic
      surgery.

PMID- 21947933
TI  - What causes myocardial infarction in women without obstructive coronary artery
      disease?

PMID- 21947934
TI  - Medical therapy of thoracic aortic aneurysms: are we there yet?

PMID- 21947935
TI  - Syndrome X and microvascular coronary dysfunction.

PMID- 21947936
TI  - Unusual location for a large cardiac fibroma.

PMID- 21947937
TI  - Cardiac involvement in granulomatosis with polyangiitis (Wegener granulomatosis).

PMID- 21947939
TI  - Letter by Ainslie et al regarding article, "Endogenous circadian rhythm in
      vasovagal response to head-up tilt".

PMID- 21947940
TI  - Letter by Dumesnil and Pibarot regarding article, "Outcome of patients with low
      gradient "severe" aortic stenosis and preserved ejection fraction".

PMID- 21947941
TI  - Letter by Daneshvar regarding article, "Outcome of patients with low-gradient
      "severe" aortic stenosis and preserved ejection fraction".

PMID- 21947942
TI  - Context-related call combinations in female Diana monkeys.
AB  - Non-human primates possess species-specific repertoires of acoustically distinct
      call types that can be found in adults in predictable ways. Evidence for vocal
      flexibility is generally rare and typically restricted to acoustic variants
      within the main call types or sequential production of multiple calls. So far,
      evidence for context-specific call sequences has been mainly in relation to
      external disturbances, particularly predation. In this study, we investigated
      extensively the vocal behaviour of free-ranging and individually identified Diana
      monkeys in non-predatory contexts. We found that adult females produced four
      vocal structures alone ('H', 'L', 'R' and 'A' calls, the latter consisting of two
      subtypes) or combined in non-random ways ('HA', 'LA' and 'RA' call combinations)
      in relation to ongoing behaviour or external events. Specifically, the
      concatenation of an introductory call with the most frequently emitted and
      contextually neutral 'A' call seems to function as a contextual refiner of this
      potential individual identifier. Our results demonstrate that some non-human
      primates are able to increase the effective size of their small vocal repertoire
      not only by varying the acoustic structure of basic call types but also by
      combining them into more complex structures. We have demonstrated this phenomenon
      for a category of vocalisations with a purely social function and discuss the
      implications of these findings for evolutionary theories of primate vocal
      communication.

PMID- 21947943
TI  - beta-Amyloid protein (Abeta) and human amylin regulation of apoptotic genes
      occurs through the amylin receptor.
AB  - Deposition of amyloid-beta (Abeta) protein, a 39-43 amino acid peptide, in the
      brain is a major pathological feature of Alzheimer's disease (AD). We have
      previously provided evidence that in primary cultures of rat basal forebrain and
      human fetal neurons (HFNs), neurotoxic effects of oligomeric Abeta are expressed
      through the amylin receptor. In this study, we utilized RT-PCR arrays to compare
      RNA expression levels of 84 markers for pro and anti- apoptotic signalling
      pathways following exposure of HFNs to either Abeta(1-42) (20 MUM) or human
      amylin (2 MUM). Oligomeric Abeta(1-42) or human amylin was applied to HFNs alone
      or after pre-treatment of cultures with the amylin receptor antagonist, AC253.
      Changes in RNA levels were then quantified and compared to each other in order to
      identify increases or decreases in gene expression of apoptotic markers.
      Applications of Abeta(1-42) or human amylin, but not the inactive inverse
      sequence Abeta(42-1) or rat amylin, resulted in a time-dependent marked increase
      in mediators of apoptosis including a 10- to 30-fold elevations in caspases 3, 6,
      9, BID and XIAP levels. Amylin receptor antagonists, AC253 (10 MUM) or AC187 (10
      MUM), significantly attenuated the induction of several pro-apoptotic mediators
      up-regulated following exposure to Abeta(1-42) or human amylin and increased the
      expression of several anti-apoptotic markers. These data allow us to identify key
      elements in the Abeta-induced apoptosis that are blocked by antagonism of the
      amylin receptor and further support the potential for amylin receptor blockade as
      a potential therapeutic avenue in AD.

PMID- 21947945
TI  - Magnetic resonance imaging of craniovertebral structures: clinical significance
      in cervicogenic headaches.
AB  - This paper aims to investigate the relevance of morphological changes in the main
      stabilizing structures of the craniocervical junction in persons with
      cervicogenic headache (CEH). A case control study of 46 consecutive persons with
      CEH, 22 consecutive with headache attributed to whiplash associated headache
      (WLaH) and 19 consecutive persons with migraine. The criteria of the Cervicogenic
      Headache International Study Group (CHISG) were used for diagnosing CEH;
      otherwise the criteria of the International Classification of Headache Disorders
      (ICHD II) were applied. All participants had a clinical interview, and physical
      and neurological examination. Proton weighted magnetic resonance imaging (MRI) of
      the craniovertebral junction, and the alar and transverse ligaments were
      evaluated and blinded to clinical information. The MRI of the craniovertebral and
      the cervical junctions, the alar and transverse ligaments disclosed no
      significant differences between those with CEH, WLaH and or migraine. The site of
      CEH pain was not correlated with the site of signal intensity changes of the alar
      and transverse ligaments. In fact, very few had moderate or severe signal
      intensity changes in their ligaments. MRI shows no specific changes of cervical
      discs or craniovertebral ligaments in CEH.

PMID- 21947947
TI  - Transferrin regulates mRNA levels of a gene involved in iron utilization in
      Entamoeba histolytica.
AB  - Entamoeba histolytica is a human pathogen, which can survive using haemoglobin
      (Hb) as only iron supply. Two probable haemophores (Ehhmbp26 and Ehhmbp45) are
      involved in iron acquisition in this parasite. However, mechanisms related to
      their transcriptional regulation have not been studied yet. In the present work,
      transcriptional profiles of both genes were evaluated in trophozoites cultures
      grown with different iron sources. ehhmbp26 gene was repressed totally by free
      iron, whereas ehhmbp45 gene showed clearly detectable mRNA levels. Expression
      profiles for both genes were significantly increased under iron privation
      condition. Interestingly, ehhmbp26 transcript was highly expressed by Holo
      transferrin presence. This induction appears to be independent of direct contact
      between these proteins, because, in vitro assays evidenced that Ehhmbp26 protein
      was unable to bind this metalloprotein. Besides, in silico analysis of promoter
      nucleotide sequences of ehhmbp26 and ehhmbp45 genes revealed some distinctive
      core promoter elements described in E. histolytica and T-rich regions. Taking
      altogether these data suggest in E. histolytica dissimilar transcriptional
      mechanisms involved on iron acquisition control the expression of these genes,
      and they are unlike to those previously described for instance: in bacteria. Our
      findings evidenced this pathogen regulates the expression of ehhmbp26 and
      ehhmbp45 genes depending on the available iron supply, always ensuring the
      success of its infective process.

PMID- 21947949
TI  - New haplotype of the complete mitochondrial genome of Crocodylus siamensis and
      its species-specific DNA markers: distinguishing C. siamensis from C. porosus in
      Thailand.
AB  - Based on molecular phylogeny of available complete mitochondrial DNA (mtDNA)
      genome sequences reveals that Crocodylus siamensis and C. porosus are closely
      related species. Yet, the sequence divergence of their mtDNA showed only a few
      values under conspecific level. In this study, a new haplotype (haplotype2,
      EF581859) of the complete mtDNA genome of Siamese crocodile (C. siamensis) was
      determined. The genome organization, which appeared to be highly similar to
      haplotype1 (DQ353946) mtDNA genome of C. siamensis, was 16,814 bp in length.
      However, the sequence divergence between the two genomes differed by around 7-10
      and 0.7-2.1% for the haplotype1 between C. siamensis and C. porosus (AJ810453).
      These results were consistent with the phylogenetic relationship among the three
      genomes, suggesting that C. siamensis haplotype1 mtDNA genome might be the hybrid
      or the intraspecific variation of C. porosus. On the other hand, our specimen was
      found to be a true C. siamensis. Simultaneously, the seven species-specific DNA
      markers designed based on the distinctive site between haplotype2 mtDNA sequences
      of C. siamensis and haplotype1 mtDNA sequence of C. siamensis-C. porosus were
      successfully used to distinguish C. siamensis from C. porosus. These effective
      markers could be used primarily for rapid and accurate species identification in
      population, ecology and conservation studies.

PMID- 21947948
TI  - Contribution of beta-globin cluster polymorphisms to raise fetal hemoglobin
      levels in normal adults.
AB  - Hereditary persistence of fetal hemoglobin (HPFH) is a group of genetically
      heterogeneous conditions characterized by continued expression of fetal
      hemoglobin (HbF) in adulthood. HPFH may be due not only to point mutations or
      large deletions in different regions of the cluster beta globin, but also to
      variations in several polymorphic sequences in this cluster. The objective of
      this work was to evaluate effects of polymorphic markers within cluster beta
      globin on HbF expression. For the purpose, we have explored in this first study
      of Tunisian HPFH four polymorphic regions of beta globin cluster in 68 healthy
      adults (34 subjects with high levels of HbF and 34 with normal HbF levels). Our
      results showed that the increase of HbF levels is associated with the -158 Ggamma
      C -> T polymorphism, the TG(18)CG(2)CACG, TC TG(9)AG TG(2)CG(2) and TG(11)CG(4)
      configurations in the second intron of Ggamma gene and the -540 beta (AT)(6)T(9)
      and (AT)(7)T(8) repeated sequences. Among the 34 subjects with raised levels of
      HbF, approximately 97% carried one or more of these six markers. This study
      suggests that there is a significant association between certain polymorphic
      configurations of the beta globin cluster and the increase of HbF levels in
      healthy individuals.

PMID- 21947950
TI  - TGF-beta superfamily: how does it regulate testis development.
AB  - Testis development is a highly regulated sequence of developmental process that
      spans from the establishment of germ cell lineage during embryonic development to
      the periodic wave of spermatogenesis in adulthood. The normal development of
      testes and the fertility of male animals require specific cell types to respond
      correctly at a specific time point, the process of which is precisely regulated
      by various factors. Several members of the transforming growth factor-beta
      superfamily are shown to be the key mediators. They act as the extracellular
      ligand of signaling transduction that regulates the proliferation,
      differentiation, apoptosis and other cell behaviors to help coordinate the
      physiology of the cells to the overall development of the testis and the
      organism. This paper reviews the current understanding of some of TGF-betas'
      major regulatory roles in the overall process of testis development, analyzes the
      current studies and their limitations and points out the research areas that need
      further investigation.

PMID- 21947952
TI  - Isolation and characterization of ten novel microsatellite loci in the red-winged
      tinamou (Rhynchotus rufescens, Tinamiformes, Aves) and cross-amplification in
      other tinamous.
AB  - We describe the isolation and characterization of ten microsatellite loci from
      the red-winged tinamou (Rhynchotus rufescens) and also evaluated the cross
      amplification of these loci and other ten loci previously developed for the great
      tinamou (Tinamus major) in other tinamous. Genetic variability was assessed using
      24 individuals. Six loci were polymorphic with moderate to high number of alleles
      per locus (2-12 alleles) and showed expected heterozygosity (HE) ranging from
      0.267 to 0.860. All loci conformed to the Hardy-Weinberg expectation and linkage
      disequilibrium was not significant for any pair of loci. This battery of
      polymorphic loci showed high paternity exclusion probability (0.986) and low
      genetic identity probability (4.95 * 10(-5)), proving to be helpful for parentage
      tests and population analyses in the red-winged tinamou. The cross-amplification
      was moderate where of the 160 locus/taxon combinations, 46 (28.75%) successfully
      amplified.

PMID- 21947951
TI  - Association and expression quantitative trait loci (eQTL) analysis of porcine
      AMBP, GC and PPP1R3B genes with meat quality traits.
AB  - The aim of this research was to screen polymorphism and to perform association
      study of porcine AMBP (alpha-1-microglobulin/bikunin precursor), GC (group
      specific component protein) and PPP1R3B (protein phosphatase 1, regulatory
      (inhibitor) subunit 3B) genes with meat quality traits as well as to unravel the
      transcriptional regulation of these genes by expression QTL (eQTL) study. For
      this purpose, Duroc * Pietrain F2 resource population (DuPi; n = 313) and a
      commercial breed Pietrain (Pi; n = 110) were used for association and only DuPi
      for expression and eQTL study. A SNP was identified in the genes AMBP
      (g.22229C>T), GC (g.398C>T) and PPP1R3B (c.479A>G), respectively. In DuPi SNP of
      AMBP was associated (P < 0.05) with meat colour, pH(1L), pH(24L), pH(24H) and
      conductivity(24L); SNP of GC showed tendency to association (P < 0.10) with
      pH24H, conductivity(1L) and thawing loss, and SNP of PPP1R3B was associated (P <
      0.05) with meat colour, pH(1L), pH(24L), pH(24H) and shear force. In Pi SNPs of
      AMBP and GC was associated with pH(24H) and PPP1R3B SNP was associated with
      pH(24L). The mRNA levels in Longissimus dorsi muscle tissue of these three genes
      were evaluated by using qRT-PCR to identify association between gene expression
      and meat quality traits as well as to analyse eQTL. The mRNA expression of
      PPP1R3B associated with pH(24L) (P < 0.05). Expression of these three genes was
      higher in animals with low pH of muscle. Linkage analysis using QTL Express
      revealed ten trans-regulated eQTL on seven porcine autosomes. Suggestive eQTL [P
      < 0.05, CW (chromosome-wide)] were found for PPP1R3B on SSC3 and 13. These
      results revealed that genetic variation and gene expression of these genes are
      associated with the meat quality traits. These three genes could influence meat
      quality and could be potential positional, physiological and functional candidate
      gene for meat quality traits in pigs. However, the analysis of eQTL also
      suggested that we need to consider additional genes encoding for transcription
      factors (TF), via fine-mapping underlying the eQTL peaks, in order to understand
      interaction among these genes.

PMID- 21947953
TI  - Metagenomic analysis of Surti buffalo (Bubalus bubalis) rumen: a preliminary
      study.
AB  - The complex microbiome of the rumen functions as an effective system for the
      conversion of plant cell wall biomass to microbial proteins, short chain fatty
      acids and gases. In this study, metagenomic approaches were used to study the
      microbial populations and metabolic potential of the microbial community. DNA was
      extracted from Surti Buffalo rumen samples (four treatments diet) and sequenced
      separately using a 454 GS FLX Titanium system. We used comparative metagenomics
      to examine metabolic potential and phylogenetic composition from pyrosequence
      data generated in four samples, considering phylogenetic composition and
      metabolic potentials in the rumen may remarkably be different with respect to
      nutrient utilization. Assignment of metagenomic sequences to SEED categories of
      the Metagenome Rapid Annotation using Subsystem Technology (MG-RAST) server
      revealed a genetic profile characteristic of fermentation of carbohydrates in a
      high roughage diet. The distribution of phylotypes and environmental gene tags
      (EGTs) detected within each rumen sample were dominated by
      Bacteroidetes/Chlorobi, Firmicutes and Proteobacteria in all the samples. The
      results of this study could help to determine the role of rumen microbes and
      their enzymes in plant polysaccharide breakdown is fundamental to understanding
      digestion and maximising productivity in ruminant animals.

PMID- 21947955
TI  - Integration of genetic and physical maps of the chickpea (Cicer arietinum L.)
      genome using flow-sorted chromosomes.
AB  - Cultivated chickpea is the third most important legume after field bean and
      garden pea worldwide. Despite considerable breeding towards improved yield and
      resistance to biotic and abiotic stresses, the production of chickpea remained
      stagnant, but molecular tools are expected to increase the impact of current
      improvement programs. As a first step towards this goal, various genetic linkage
      maps have been established and markers linked to resistance genes been
      identified. However, until now, only one linkage group (LG) has been assigned to
      a specific chromosome. In the present work, mitotic chromosomes were sorted using
      flow cytometry and used as template for PCR with primers designed for genomic
      regions flanking microsatellites. These primers amplify sequence-tagged
      microsatellite site markers. This approach confirmed the assignment of LG8 to the
      smallest chromosome H. For the first time, LG5 was linked to the largest
      chromosome A, LG4 to a medium-sized chromosome E, while LG3 was anchored to the
      second largest chromosome B. Chromosomes C and D could not be flow-sorted
      separately and were jointly associated to LG6 and LG7. By the same token,
      chromosomes F and G were anchored to LG1 and LG2. To establish a set of
      preferably diagnostic cytogenetic markers, the genomic distribution of various
      probes was verified using FISH. Moreover, a partial genomic bacterial artificial
      chromosome (BAC) library was constructed and putative single/low-copy BAC clones
      were mapped cytogenetically. As a result, two clones were identified localizing
      specifically to chromosomes E and H, for which no cytogenetic markers were yet
      available.

PMID- 21947954
TI  - Anchoring the dog to its relatives reveals new evolutionary breakpoints across 11
      species of the Canidae and provides new clues for the role of B chromosomes.
AB  - The emergence of genome-integrated molecular cytogenetic resources allows for
      comprehensive comparative analysis of gross karyotype architecture across related
      species. The identification of evolutionarily conserved chromosome segment (ECCS)
      boundaries provides deeper insight into the process of chromosome evolution
      associated with speciation. We evaluated the genome-wide distribution and
      relative orientation of ECCSs in three wild canid species with diverse karyotypes
      (red fox, Chinese raccoon dog, and gray fox). Chromosome-specific panels of dog
      genome-integrated bacterial artificial chromosome (BAC) clones spaced at ~10-Mb
      intervals were used in fluorescence in situ hybridization analysis to construct
      integrated physical genome maps of these three species. Conserved evolutionary
      breakpoint regions (EBRs) shared between their karyotypes were refined across
      these and eight additional wild canid species using targeted BAC panels spaced at
      ~1-Mb intervals. Our findings suggest that the EBRs associated with speciation in
      the Canidae are compatible with recent phylogenetic groupings and provide
      evidence that these breakpoints are also recurrently associated with spontaneous
      canine cancers. We identified several regions of domestic dog sequence that share
      homology with canid B chromosomes, including additional cancer-associated genes,
      suggesting that these supernumerary elements may represent more than inert
      passengers within the cell. We propose that the complex karyotype rearrangements
      associated with speciation of the Canidae reflect unstable chromosome regions
      described by the fragile breakage model.

PMID- 21947956
TI  - Nuclear organisation of sperm remains remarkably unaffected in the presence of
      defective spermatogenesis.
AB  - Organisation of chromosome territories in interphase nuclei has been studied in
      many systems and positional alterations have been associated with disease
      phenotypes (e.g. laminopathies, cancer) in somatic cells. Altered nuclear
      organisation is also reported in developmental processes such as mammalian
      spermatogenesis where a "chromocentre" model is proposed with the centromeres and
      sex chromosomes repositioning to the nuclear centre. The purpose of this study
      was to test the hypothesis that alterations in nuclear organisation of human
      spermatozoa are associated with defects upstream in spermatogenesis (as manifest
      in certain infertility phenotypes). The nuclear address of (peri-) centromeric
      loci for 18 chromosomes (1-4, 6-12, 15-18, 20, X and Y) was assayed in 20 males
      using established algorithms for 3D extrapolations of 2D data. The control group
      comprised 10 fertile sperm donors while the test group was 10 patients with
      severely compromised semen parameters including high sperm aneuploidy. All loci
      examined in the control group adopted defined, interior positions thus providing
      supporting evidence for the presence of a chromocentre and interior sex
      chromosome territories. In the test group however there were subtle alterations
      in the nuclear address for certain centromeres in individual patients and, when
      all patient results were pooled, some different nuclear addresses were observed
      for chromosomes 3, 6, 12 and 18. Considering the extensive impairment of
      spermatogenesis in the test group (evidenced by compromised semen parameters and
      increased chromosome abnormalities), the observed differences in nuclear
      organisation for centromeric loci compared to the controls were modest. A defined
      pattern of nuclear reorganisation of centromeric loci in sperm heads therefore
      appears to be a remarkably robust process, even if spermatogenesis is severely
      compromised.

PMID- 21947957
TI  - Inactivation of a centromere during the formation of a translocation in maize.
AB  - Fluorescence in situ hybridization analysis of a reciprocal translocation in
      maize between chromosomes 1 and 5 that has been used extensively in maize
      genetics revealed the presence of an inactive centromere at or near the
      breakpoints of the two chromosomes. This centromere contains both the satellite
      repeat, CentC, and the centromeric retrotransposon family, CRM, that are typical
      of centromere regions in maize. This site does not exhibit any of the tested
      biochemical features of active centromeres such as association with CENP-C and
      phosphorylation of serine-10 on histone H3. The most likely scenario for this
      chromosome arrangement is that a centromere was included in the repair process
      that formed the translocation but became inactive and has been inherited in this
      state for several decades. The documentation of an inactive A chromosome
      centromere in maize extends the evidence for an epigenetic component to
      centromere function in plants. This case provides an experimental example of how
      karyotype evolution might proceed via changes in centromere inactivation.

PMID- 21947959
TI  - Pig performance increases with the addition of DL-methionine and L-lysine to
      ensiled cassava leaf protein diets.
AB  - Two studies were conducted to determine the impact of supplementation of diets
      containing ensiled cassava leaves as the main protein source with synthetic amino
      acids, DL-methionine alone or with L-lysine. In study 1, a total of 40 pigs in
      five units, all cross-breds between Large White and Mong Cai, with an average
      initial body weight of 20.5 kg were randomly assigned to four treatments
      consisting of a basal diet containing 45% of dry matter (DM) from ensiled cassava
      leaves (ECL) and ensiled cassava root supplemented with 0%, 0.05%, 0.1% and 0.15%
      DL-methionine (as DM). Results showed a significantly improved performance and
      protein gain by extra methionine. This reduced the feed cost by 2.6%, 7.2% and
      7.5%, respectively. In study 2, there were three units and in each unit eight
      cross-bred (Large White * Mong Cai) pigs with an initial body weight of 20.1 kg
      were randomly assigned to the four treatments. The four diets were as follows: a
      basal diet containing 15% ECL (as DM) supplemented with different amounts of
      amino acids L-lysine and DL-methionine to the control diet. The results showed
      that diets with 15% of DM as ECL with supplementation of 0.2% lysine +0.1% DL
      methionine and 0.1% lysine +0.05% DL-methionine at the 20-50 kg and above 50 kg,
      respectively, resulted in the best performance, protein gain and lowest costs for
      cross-bred (Large White * Mong Cai) pigs. Ensiled cassava leaves can be used as a
      protein supplement for feeding pigs provided the diets contain additional amounts
      of synthetic lysine and methionine.

PMID- 21947958
TI  - Illuminating the gateway of gene silencing: perspective of RNA interference
      technology in clinical therapeutics.
AB  - A novel laboratory revolution for disease therapy, the RNA interference (RNAi)
      technology, has adopted a new era of molecular research as the next generation
      "Gene-targeted prophylaxis." In this review, we have focused on the chief
      technological challenges associated with the efforts to develop RNAi-based
      therapeutics that may guide the biomedical researchers. Many non-curable
      maladies, like neurodegenerative diseases and cancers have effectively been cured
      using this technology. Rapid advances are still in progress for the development
      of RNAi-based technologies that will be having a major impact on medical
      research. We have highlighted the recent discoveries associated with the
      phenomenon of RNAi, expression of silencing molecules in mammals along with the
      vector systems used for disease therapeutics.

PMID- 21947960
TI  - Proteomic analyses of Sirt1-mediated cisplatin resistance in OSCC cell line.
AB  - Oral squamous cell carcinoma (OSCC) accounts for about 90% of malignant oral
      lesions, and is recognized as the third most common cancer in developing nations
      and the sixth most common cancer worldwide. While chemotherapy remains the
      primary treatment for both resectable and advanced OSCC, most OSCC are naturally
      resistant to anticancer drugs, rendering new therapeutic avenues in dire need.
      Sirt1, a class III histone deacetylase, was linked to cisplatin resistance in
      several cancer types; however, the underlying mechanism is still unclear. Here,
      we demonstrated that overexpression of Sirt1 survived OSCC cell line Tca8113
      under cisplatin treatment. Notably, BML-210, a chemical inhibitor of class III
      histone deacetylase, significantly abolished Sirt1-mediated cisplatin resistance
      in Tca8113 cells. Further, inactivation of endogenic Sirt1 by nicotinamide
      markedly increased chemo-sensitivity in cisplatin resistant sub-cell line
      Tca8113/CDDP. Proteomic strategy was applied to profile the differentially
      expressed proteins between pcDNA3.1-Sirt1- and mock vector-treated Tca8113 cells.
      Among 54 spots identified, 31 proteins were up-regulated and 23 proteins were
      down-regulated upon Sirt1 expression. Expression of four proteins with most
      significant alteration, including Annexin A4, Stathmin, SOD2 and thioredoxin,
      were validated by both RT-PCR and Western blot. Finally, we showed that Sirt1
      could prevent cisplatin-induced ROS accumulation in Tca8113 cells. Our findings
      are considered as a significant step toward a better understanding of Sirt1
      mediated cisplatin resistance.

PMID- 21947962
TI  - Elevated levels of oxidized low-density lipoprotein correlate positively with C
      reactive protein in patients with acute coronary syndrome.
AB  - The relationship between oxidized low-density lipoprotein (Ox-LDL) and C-reactive
      protein (CRP) in patients with acute coronary syndrome (ACS) is unknown. We,
      therefore, measured serum levels of Ox-LDL and high-sensitivity (hs)-CRP in 90
      ACS patients, 45 stable angina pectoris (SAP) patients, and 66 healthy controls
      using sandwich ELISA. ACS patients were subdivided into: (1) acute myocardial
      infarction (AMI; n = 45); (2) unstable angina pectoris (UAP; n = 45) groups. In
      AMI patients, Ox-LDL (177.5 mmol/l) and hs-CRP (25.40 mg/l) levels were
      significantly higher (P < 0.01) than in UAP (Ox-LDL:107.5 mmol/l, hs-CRP:10.7
      mg/l) and SAP (Ox-LDL:82.3 mmol/l, hs-CRP:2.10 mg/l) patients as well as controls
      (Ox-LDL:41.4 mmol/l, hs-CRP:1.76 mg/l). Ox-LDL/hs-CRP levels in UAP patients were
      significantly higher (P < 0.01) than in SAP patients and controls. Importantly, a
      positive correlation was found between Ox-LDL and CRP (r = 0.622; P < 0.01)
      levels. Serum levels of total, HDL, and LDL cholesterol did not differ among
      these patient groups. In conclusion, our data show that Ox-LDL and hs-CRP levels
      correlate positively in ACS patients, supporting the hypothesis that Ox-LDL and
      CRP may play a direct role in promoting the inflammatory component of
      atherosclerosis in these individuals. We suggest that Ox-LDL/CRP elevated levels
      may serve as markers of the severity of the disease in evaluation and management
      of ACS patients.

PMID- 21947961
TI  - Hyperhomocysteinemia and related genetic polymorphisms correlate with ulcerative
      colitis in Chinese Han population in Central China [corrected].
AB  - Increased levels of homocysteine are found systemically and in intestinal mucosa
      of patients with inflammatory bowel disease, and, specifically, in ulcerative
      colitis (UC). However, there are controversial reports regarding the factors
      contributing to increased levels of homocysteine in UC. Furthermore, little
      information is available regarding the relationship between hyperhomocysteinemia
      (HHcy), vitamin status, and genetic polymorphisms of homocysteine-related enzymes
      in these patients. This study examined four functional polymorphisms linked to
      homocysteine metabolism (MTHFR C677T and A1298C, MTR A2756G and MTRR A66G), and
      evaluated plasma levels of homocysteine, folate, and vitamin B(12) in 310
      consecutive patients with UC and 936 age- and sex-matched healthy controls from
      southeast China. The variant allele and genotypic frequencies in MTHFR A1298C,
      MTR A2756G and MTRR A66G genes were significantly higher in patients with UC
      compared to healthy controls. Further, HHcy and low levels of folate and vitamin
      B(12) were more frequent in patients with UC. The MTR 2756G allele, extent of the
      disease, and gender were the independent determinants of HHcy in these patients.
      These findings suggest that genetic and nutritional factors have a synergetic
      effect on HHcy in patients with UC. In conclusion, our data highlight a
      prevention strategy for moderation of HHcy and supplementation with folate and
      vitamine B(12) in patients with UC from Southeast China.

PMID- 21947963
TI  - Effect of pulmonary-generated reactive oxygen species on left-ventricular
      dysfunction associated with cardio-pulmonary ischemia-reperfusion injury.
AB  - The purpose of the present study was to demonstrate the contribution of pulmonary
      generated reactive oxygen species (ROS) on cardiac dysfunction using a rat model
      of ischemia-reperfusion (IR) injury. Three groups of rats were subjected to
      regional IR injury in (i) lung, (ii) heart, (iii) lung + heart. A fourth
      (control) group of rats were instrumented using the same methods but without
      induction IR. Hemodynamic data were recorded in real time. Blood from the
      proximal aorta was sampled during baseline, ischemia, and reperfusion, mixed with
      alpha-phenyl-N-tert-butylnitrone (PBN) for measuring ROS by electron paramagnetic
      resonance spectrometry. Data were analyzed by a two-way analysis of variance. The
      results showed that the lung IR generated an increased burst of ROS that resulted
      in significant cardiac dysfunction, including hypotension and ECG changes. The
      results indicated that generation of ROS as a result of acute IR lung injury may
      be sufficiently large enough to cause direct cardiac dysfunction that is
      independent of injury caused to the myocardium as a result of regional myocardial
      IR injury alone. 

PMID- 21947964
TI  - The changing understanding of ageing. Part 1: Evaluating ageing theories and
      studies.
AB  - This is the first of three discussions on emerging views of ageing, its
      derivation, and ageing-related diseases. To offer a context for the series, this
      first report briefly reviews several major early and recent theoretical debates.
      Arguments for and against several well-known ageing theories are presented for
      their veterinary relevance, including mutation, pleiotropy, reproduction
      longevity trade-offs, oxygen metabolism and ageing as a genomically programmed
      product of natural selection. Additionally, the author presents commonly
      encountered problems when reading to interpret laboratory and population studies
      of ageing, offering busy clinicians a perspective on evaluating complex papers
      that analyse ageing-related data. Included among these problems are categorising
      intrinsic and extrinsic diseases, contrasts between laboratory-based and
      population-based observations, over-generalising research outcomes, short-term
      and long-term studies, and theoretical treatises. Central ideas of these
      discussions include why post-reproductive life span is relatively common among
      animals, the nature of age-related diseases relative to stochastic or programmed
      origins and the disease-related implications.

PMID- 21947965
TI  - The changing understanding of ageing. Part 2: Body composition, metabolism and
      cell death.
AB  - This second of three discussions about ageing biology and diseases continues at
      the level of the organism, examining the relationship among body composition,
      late life and diseases. One view of significant age-related mass loss in humans
      suggests that anabolic failure is associated with various precipitating factors
      that may share anorexia in common. Lean mass decline with even partial anorexia
      should alert clinicians to monitor patients for emergence of otherwise
      subclinical disease. Weight or mass loss and clinical disease also may be
      independent, thus creating an interwoven and complex view. Recent data from the
      Portuguese water dog genetics model suggest that heritable factors play a role in
      end of life body metrics and some histological changes, and that some metric and
      histological changes are themselves inter-related. While widespread inflammation
      and hyperplasia were less frequent than expected, there exists nonetheless a
      disease relationship to the growth hormone (GH)-insulin-like growth factor (IGF
      1)-insulin axis that requires further exploration. Oxidative metabolism and
      apoptosis are reviewed briefly as examples at the cellular level that may be
      reflected in gross ageing phenotypes, further underscoring the complex nature of
      many late-life diseases.

PMID- 21947966
TI  - The changing understanding of ageing. Part 3: Diseases of ageing.
AB  - This third and final paper in this series considers ageing mechanisms across
      species, with emphasis on conserved metabolic pathways that relate to disease.
      The growth hormone (GH)-insulin-like growth factor (IGF-1)-insulin axis continues
      as an example of how critical pathways might relate to longevity and senescence.
      Aligning theory, research outcomes and clinical investigations at the levels of
      the cell, organism and population, is suggested as a means by which to consider
      the many complexities of the ageing process in an orderly fashion. A contentious
      debate revolves around whether ageing is purely a combined effect of stochastic
      events on residual programming relating to reproductive robustness, or whether
      ageing itself is programmed by natural selection. Emerging data indicate that the
      influence of genetic programming on specific late-life diseases, and even
      individual tissue pathologies, will probably need to be reconsidered in the light
      of newer theoretical possibilities. In particular, the evidence that late life
      and its diseases are objects of considerable investment of energy challenges
      theory that couples longevity with reproduction. Furthermore, the author suggests
      that ageing may have evolved at least partly as a means of niche preservation for
      contemporaries and for progeny.

PMID- 21947967
TI  - Development and validation of an antigen capture ELISA based on monoclonal
      antibodies specific for Listeria monocytogenes in food.
AB  - A capture enzyme-linked immunosorbent assay (ELISA) for the identification of
      Listeria monocytogenes in food was standardised and validated. The assay was
      refined by analysing samples of meat, seafood, dairy products, pasta and flour.
      The method was found to be 100% specific for Listeria spp. tested, with a limit
      of sensitivity of 6.6 * 10(3) colony-forming units (cfu)/ml. Comparison of L.
      monocytogenes capture ELISA against the official International Organization for
      Standardization (ISO) method 11290-1:1996 for the isolation and identification of
      L. monocytogenes in food matrices produced a significant concordance index. The
      assay was validated on food matrices including meat, seafood and dairy products
      in line with ISO 16140:2003 concerning qualitative analytical methods. The assay
      was found to be accurate, specific, sensitive, selective, reproducible and fast,
      resulting in lower costs and faster turnaround in microbiological screening of
      foods.

PMID- 21947968
TI  - The national information system for the notification of animal diseases in Italy.
AB  - This paper describes the national system for the notification and management of
      outbreaks of animal diseases in Italy (Sistema Informativo Nazionale Malattie
      Animali: SIMAN). The main objective of the system is to provide a tool for the
      management of epidemic emergencies and to fulfil the information obligations
      towards international organisations, such as the European Commission and World
      Organisation for Animal Health (Office International des Epizooties: OIE). SIMAN
      was thus designed to collect all relevant information on outbreaks of animal
      diseases and to provide a useful tool for the management of activities to be
      implemented in emergencies. SIMAN is able to collect and report information
      concerning suspected or confirmed animal outbreaks in a consistent way and allows
      veterinary services to enter data electronically, instead of using paperwork,
      within the framework of the process of e-government and dematerialisation of the
      administrative acts. Data are immediately accessible for local and national
      authorities. The system provides the relevant national authorities with
      information relative to the planning of control measures in case epidemic
      emergencies. SIMAN is part of the e-government process that involves all public
      administrations of the European Union (EU) and refers to the use of information
      and communication technologies for the digital processing of documents so as to
      simplify the system and to make administrative procedures on the Internet much
      easier to follow.

PMID- 21947969
TI  - Use of real-time polymerase chain reaction to detect bovine herpesvirus 1 in
      frozen cattle and buffalo semen in India.
AB  - Bovine herpesvirus 1 (BoHV-1) infection in cattle and buffalo makes these animals
      life-long carriers of the virus which is intermittently excreted in semen. In the
      present study, a real-time polymerase chain reaction (PCR) was validated to
      screen frozen semen from cattle and buffalo for BoHV-1 by amplification of the gB
      gene of the virus. Analysing the intra- and inter-test variability, the assay was
      found to be highly reproducible. High sensitivity (100%) and specificity (90.04%)
      of this real-time PCR assay was recorded in comparison to virus isolation.
      Extended frozen semen samples from 574 cattle and buffalo bulls that were
      seropositive to infectious bovine rhinotracheitis (IBR) tested by real-time PCR
      indicated that 1.97% semen batches from cattle and 3.36% batches of buffalo semen
      were positive for BoHV-1. The real-time PCR protocol will be useful for screening
      large numbers of semen samples from IBR-seropositive cattle and buffalo bulls as
      the test is less time consuming and several batches of semen can be tested with
      ease compared to virus isolation in cell culture.

PMID- 21947970
TI  - Sequence and phylogenetic analyses of an Indian isolate of orf virus from sheep.
AB  - The authors describe the isolation and identification of orf virus (ORFV) from an
      outbreak in a flock of sheep at Mukteswar, Uttarakhand, India, in 2009. The
      causative agent, ORFV was successfully isolated in primary lamb testes cells and
      identified using a semi-nested diagnostic polymerase chain reaction (PCR) and
      sequence and phylogenetic analyses of immunogenic envelope protein (B2L) coding
      gene. The affected animals showed characteristic proliferative skin lesions
      around the mouth and on nostrils and, in a few animals, lesions were also noticed
      on the tongue irrespective of age and sex. The morbidity, mortality and case
      fatality rates observed were 6%, 45% and 13%, respectively. Clinical samples were
      initially screened by counter immuno-electrophoresis and the serum neutralisation
      test; further positive skin scabs were tested with diagnostic PCR and virus
      isolation was performed on primary or secondary lamb testes cultures. Sequencing
      and phylogenetic analyses of the sheep isolate based on the B2L gene revealed
      that the isolate was closest to a goat isolate retrieved from an outbreak at the
      same geographic location in 2000. Furthermore, it also showed close genetic
      similarities with other Indian isolates reported earlier. Regular and systematic
      investigation of outbreaks is necessary to monitor the disease in susceptible
      populations. The development of rapid diagnostic methods as well as effective
      vaccine to control this infection not only from India but also other parts of the
      world is called for.

PMID- 21947971
TI  - Survey on coenurosis in sheep and goats in Egypt.
AB  - A total of 75 sheep and goats from apparently healthy and from clinically
      affected flocks were examined for Coenurus cerebralis cysts from different
      localities in Egypt. Of 25 animals examined from clinically diseased sheep and
      goats, 25 (100%) revealed the presence of infestation with one to four coenuri in
      the brain. The sites of predilection were the left hemisphere (48%), followed by
      the right hemisphere (40%) and the cerebellum (12%). There was no apparent effect
      of the age of sheep and goats on susceptibility to infestation with C.
      cerebralis. Another 50 animals from apparently healthy sheep and goat herds
      presented no C. cerebralis cysts. The cysts from infested sheep could infest
      newborn puppies experimentally, with a prepatent period of 60 days post
      infestation. A total of 15 immature worms that were recovered from one puppy did
      not reach patency until 105 days post infestation with C. cerebralis cyst
      scolices. Pathological changes in C. cerebralis-infested sheep brain revealed
      parasitic elements, demyelinated nerve tracts, hyperaemic blood vessels with
      round cell infiltration, encephalomalacia with round cell infiltration and
      palisading macrophages and giant cells, as well as focal replacement of the brain
      parenchyma with caseated and calcified materials. The morphological
      characteristics of both the larval stage from sheep and goats and adult worms of
      Taenia multiceps from experimentally infested dogs are described. The results
      conclude that C. cerebralis is one of the principal causes of nervous
      manifestations of coenurosis in clinically diseased sheep and goats in Egypt.

PMID- 21947972
TI  - Anti-tumour effects of Egyptian propolis on Ehrlich ascites carcinoma.
AB  - A total of 150 female Swiss mice were used to study the ability of water soluble
      propolis derivatives (WSPD) of Egyptian propolis to inhibit the proliferation and
      growth of Ehrlich ascites carcinoma (EAC) cells in mice. The mice were divided
      equally into three groups: the first was kept as a negative control group, the
      second received an intraperitoneal injection of 2.5 * 10(6) EAC and was kept as a
      positive control group and the third an intraperitoneal injection of 2.5 * 10(6)
      EAC and treated with propolis (50 mg/kg body weight) administered by gastric
      intubations 2 h prior to the intraperitoneal injection of EAC. The propolis was
      administered daily for 11 successive days. An examination of EAC cells revealed a
      reduction in the volume, total cell count, viable percentage and increase in the
      percentage of dead cells in the treated group with an increasing mean survival
      time (MST), increasing life span (ILS) percentage and treated vs positive control
      (T/C) percentage. Immunological studies revealed a significant increase in the
      lymphocyte transformation rate (LTR), phagocytic activity and killing power in
      the group treated with propolis. A haematological study of the parameters
      revealed leucocytosis in cancer-bearing mice and propolis-treated groups with
      granulocytosis and monocytosis. The erythrogram revealed a significant reduction
      in red blood cell (RBC) count in group 2. The result showed that the implantation
      of EAC in Swiss mice without treatment resulted in a significant decrease in
      total protein and albumin levels without a change in globulin level and a
      significant increase in creatinine level, while the third group that received
      propolis showed an improvement in these biochemical parameters compared to the
      normal control group.

PMID- 21947973
TI  - Heavy metal residues in beef carcasses in Beni-Suef abattoir, Egypt.
AB  - A total of 300 samples were collected from cattle slaughtered in the Beni-Suef
      abattoir in Egypt. Samples included muscle, liver and kidney. Animals were
      randomly selected from the slaughter line. The age of the slaughtered cattle was
      less than three years (18-30 months). Samples were packed separately in plastic
      bags, identified and stored at -18 degrees C until analysis which was performed
      at the Max Rubner Institute in Kulmbach, Germany, for the following heavy metals
      residues: lead, cadmium, mercury, arsenic, chromium and nickel in beef muscle,
      liver and kidney samples. The results revealed that the overall mean residual
      levels of lead were 8.77 ug/kg, 42.70 ug/kg and 109.42 ug/kg fresh weight in
      muscle, liver and kidney samples, respectively, while the mean residual levels of
      cadmium were 1.40 ug/kg, 14.16 ug/kg and 62.56 ug/kg fresh weight, respectively,
      and the mean arsenic residual levels were 5.06 ug/kg, 4.64 ug/kg and 14.92 ug/kg
      fresh weight, respectively. The mean residual levels of mercury were 3.91 ug/kg,
      5.81 ug/kg and 10.14 ug/kg fresh weight, respectively, and the residual levels of
      chromium were 11.20 ug/kg, 21.85 ug/kg and 25.49 ug/kg fresh weight,
      respectively. Finally, the mean residual levels of nickel were 21.17 ug/kg, 14.59
      ug/kg and 34.95 ug/kg fresh weight, respectively. The mean values of all heavy
      metals examined were low and did not exceed the permissible limits adopted by
      different organisations. Most heavy metals accumulated in higher concentrations
      in the kidney in comparison to the liver and muscle.

PMID- 21947974
TI  - Detection of Vibrio splendidus and related species in Chamelea gallina sampled in
      the Adriatic along the Abruzzi coastline.
AB  - Vibrio species are an important and widespread component of marine microbial
      communities. Some Vibrio strains are potentially pathogenic to marine vertebrates
      and invertebrates. The aim of this study was to identify vibrios, in particular
      Vibrio splendidus and related species, isolated from clams (Chamelea gallina)
      collected along the coasts of the Abruzzi region from May to October 2007. The
      isolates obtained were phenotyped and classified as belonging to the genus
      Vibrio. The strains underwent biochemical testing in accordance with Alsina's
      scheme for V. splendidus identification. Molecular analysis of the 16S-23S
      intergenic space region and recA gene was used to identify V. splendidus and
      related species. All the samples examined were found to contain halophylic Vibrio
      species, with V. alginolyticus, V. splendidus-related species and V. mediterranei
      most commonly found. A polymerase chain reaction of the 16S-23S intergenic space
      region and sequencing of the recA gene from isolates confirmed that phenotyping
      of Vibrio species is not sufficient to distinguish between different species.
      Differentiation of the highly related species among V. splendidus-related
      clusters remains an important issue. In this regard, our data suggests sequencing
      the recA genes was far more discriminatory than sequencing 16S rDNA for this
      purpose.

PMID- 21947975
TI  - Psychosocial correlates of HIV-monoinfection and HIV/HCV-coinfection among men
      who have sex with men.
AB  - Rates of hepatitis C virus (HCV) among HIV-positive men who have sex with men
      (MSM) appear to be high and rising. In other demographic groups, HIV/HCV
      coinfection is associated with poor physical and psychological outcomes. In this
      study, we examined health-related and psychosocial correlates of HIV/HCV
      coinfection in a clinic sample of MSM. Cross-sectional data were collected from
      171 MSM. One-third of the sample was coinfected. Higher rates of depressive and
      PTSD symptoms were observed in coinfected patients. Coinfected men were more
      likely to report perfect 30-day medication adherence, but exhibited lower CD4
      cell counts and more past year emergency room visits. Despite consistent
      engagement with care and higher rates of medication adherence, HIV/HCV-coinfected
      MSM exhibited significantly more mental health problems. Medical and mental
      health providers should be especially attentive to the mental health status of
      HIV/HCV-coinfected MSM, despite adequate health behaviors and physical health
      status.

PMID- 21947976
TI  - Optimization of extractants, purifying packings, and eluents for analytical
      extraction of organochlorine pesticides in Hydragric Acrisols.
AB  - In this study, we screened for an economic, rapid, and efficient hypotoxic
      pretreatment method for organochlorine pesticides in soil samples for gas
      chromatography (GC) analysis. The analytical extraction efficiencies of 11
      different extractants, nine types of solid-phase purification (SPP) cartridge
      packings, and three types of eluents for 13 organochlorine pesticides (OCPs) in
      spiked and natural Chinese red soil (Hydragric Acrisols) were evaluated using an
      ultrasonic extraction and solid-phase purification method. High percent
      recoveries (85-106%) were obtained for the 13 organochlorine pesticides in soil
      when petroleum ether/acetone/water (10:5:2, v/v) was used an extractant. They
      were purified using celite SPP cartridge packing and eluted with 9 mL of
      dichloromethane/petroleum ether (1:9, v/v). The OCPs purification pretreatment of
      Hydragric Acrisols, using the above method, meets the GC analysis requirements.
      Compared with other traditional pretreatment methods for OCPs in soil samples,
      this method has several advantages, such as a short extraction time, reducing the
      amount of solvent, having no emulsion phenomenon, and hypotoxicity to the
      laboratory technicians. The concentrations of 1,1,1,-trichloro-2(p-chlorophenyl)
      2-(o-chlorophenyl) ethane (DDTs; 3.42-8.08 ng g(-1)) in field soils were higher
      than the hexachlorocyclohexane concentration (2.94-6.12 ng g(-1)). The 1,1
      dichloro-2,2-bis(p-chlorophenyl) ethylene (p,p'-DDE) + 1,1-dichloro-2,2-bis(p
      chlorophenyl)-ethane (p,p'-DDD)/p,p'-DDT ratio in this field soil was
      approximately 2.7, suggesting that no new DDT pollution source was introduced
      into the sampling site.

PMID- 21947977
TI  - Elevated skeletal muscle apoptotic signaling following glutathione depletion.
AB  - Oxidative stress has a well-established role in numerous intracellular signaling
      pathways, including apoptosis. Glutathione is an important cellular antioxidant
      and is the most abundant low molecular weight thiol in the cell. Although
      previous work has shown a link between glutathione and apoptosis, this
      relationship has not been defined in skeletal muscle. The present investigation
      examined the effect of glutathione depletion on skeletal muscle apoptotic
      signaling, and mitochondrial apoptotic-susceptibility. Administration of L: 
      buthionine-[S,R]-sulfoximine (BSO; 30 mM in drinking water for 10 days) caused
      glutathione depletion in whole muscle and isolated mitochondria, as well as
      elevated muscle catalase protein content and reactive oxygen species (ROS)
      generation. Glutathione depletion was associated with elevated DNA fragmentation,
      mitochondrial Bax levels, Poly(ADP-ribose) polymerase (PARP) cleavage, and
      calpain activity; however, caspase-3, -8, and -9 activity were not altered. BSO
      administration was also associated with higher cytosolic and nuclear protein
      levels of apoptosis-inducing factor (AIF), but not cytochrome c, second
      mitochondria-derived activator of caspase (Smac), or endonuclease G (EndoG). In
      addition, isolated mitochondria from BSO animals demonstrated significantly lower
      membrane potential, increased Ca(2+)-induced permeability transition pore
      opening, and greater basal and ROS-induced AIF and cytochrome c release. These
      results demonstrate that glutathione depletion in skeletal muscle increases
      caspase-independent signaling, as well as augments mitochondrial-associated
      apoptotic events to subsequent cell death stimuli.

PMID- 21947978
TI  - Electrocardiographic changes during vasodilator SPECT myocardial perfusion
      imaging: does it affect diagnosis or prognosis?
AB  - BACKGROUND: Significance of electrocardiographic (ECG) changes during vasodilator
      stress myocardial perfusion imaging (MPI) is controversial. We examined the
      diagnostic and prognostic significance of ECG changes during vasodilator single
      photon emission computerized tomography (SPECT) MPI. METHODS: We studied
      consecutive patients who underwent vasodilator SPECT MPI from 1995 to 2009.
      Patients with baseline ECG abnormalities, previous history of coronary artery
      bypass graft surgery or myocardial infarction (MI) were excluded. Significant
      coronary artery disease (CAD) was defined as >70% stenosis of any vessel or >=50%
      stenosis of left main. Mean follow-up was 2.4 +/- 1.5 years for cardiac events
      (cardiac death and non-fatal MI). RESULTS: Of patients in the diagnostic cohort,
      ST depression was associated with increased incidence of CAD with abnormal (P =
      .020 and P <.001) but not in those with normal perfusion (P = .342). Of 3,566
      patients with follow-up in the prognostic cohort, including 130 (5.0%) with ST
      depression and normal perfusion, the presence of ST depression >=1 mm did not
      affect the outcomes in any summed stress score category. CONCLUSIONS: ST
      depression >=1 mm during vasodilator SPECT MPI is associated with CAD in patients
      with abnormal perfusion, but provides no additional risk stratification beyond
      concomitant perfusion imaging, including those with normal studies.

PMID- 21947979
TI  - Archaeal transcriptional regulation of the prokaryotic KdpFABC complex mediating
      K(+) uptake in H. salinarum.
AB  - The genome of the halophilic archaeon Halobacterium salinarum encodes the high
      affinity ATP-dependent K(+) uptake system Kdp. Previous studies have shown that
      the genes coding for the KdpFABC complex are arranged in a kdpFABCQ gene cluster
      together with an additional gene kdpQ. In bacteria, expression of the kdpFABC
      genes is generally regulated by the dedicated sensor kinase/response regulator
      pair KdpD/KdpE, which are absent in H. salinarum. Surprisingly, H. salinarum
      expresses the kdp genes in a manner which is strikingly similar to Escherichia
      coli. In this study, we show that the halobacterial kdpFABCQ genes constitute an
      operon and that kdpFABCQ expression is subject to a complex regulatory mechanism
      involving a negative transcriptional regulator and is further modulated via a so
      far unknown mechanism. We describe how the regulation of kdp gene expression is
      facilitated in H. salinarum in contrast to its bacterial counterparts. Whereas
      the Kdp system fulfils the same core function as an ATP-driven K(+) uptake system
      in both archaea and bacteria, the different mechanisms involved in the regulation
      of gene expression appear to have evolved separately, possibly reflecting a
      different physiological role of ATP-driven K(+) uptake in halophilic archaea.

PMID- 21947981
TI  - Implantable cardioverter-defibrillator therapy in the elderly: the continuing
      quest for data.

PMID- 21947980
TI  - Renal function and adaptive changes in patients after radical or partial
      nephrectomy.
AB  - INTRODUCTION: Renal function after renal surgery depends on the volume of renal
      parenchyma loss and improves in the postoperative period. However, the knowledge
      on kidney function after radical (RN) and partial (PN) nephrectomy is still
      insufficient. The aim of this study is to analyze the global renal function and
      compensatory hyperfunction of the non-operated kidney in patients with renal
      cancer after RN or PN. METHODS: Fifty-one patients of mean age 62.2 years with
      renal cancer were included. Thirty-three RN and eighteen PN were performed. We
      measured creatinine serum concentrations, and we estimated glomerular filtration
      rate (eGFR) preoperatively and postoperatively at two time intervals: 3 and 12
      months after surgery. Additionally, we assessed effective renal plasma flow
      (ERPF) in dynamic scintigraphy preoperatively and 12 months after surgery.
      RESULT: At the baseline, all mean measured values were comparable in RN and PN
      groups (P > 0.05). Three months after surgery, creatinine level increased in both
      groups, more remarkably in RN group (128 mmol/l vs. 95 mmol/l; P < 0.05), while
      eGFR diminished (47 ml/min/1.73 m(2) vs. 70 ml/min/1.73 m(2); P < 0.05). Similar
      biochemical values were observed 12 months after surgery. The mean ERPF of the
      non-operated kidney 12 months after surgery in RN and PN groups increased by 3.8%
      (232 ml/min) and 0.1% (200 ml/min), respectively (P > 0.05). The mean ERPF of the
      operated kidney in PN group decreased by 24.7% (149 ml/min). CONCLUSION: The
      deterioration of renal function after partial nephrectomy is nearly insignificant
      clinically. In 1-year postoperative observation, the renal function does not
      improve. This causes potential compensatory mechanisms to be insufficient.

PMID- 21947982
TI  - Usefulness of the 12-lead electrocardiogram in the follow-up of patients with
      cardiac resynchronization devices. Part I.
AB  - Cardiac resynchronization therapy (CRT) has added a new dimension to the
      electrocardiographic evaluation of pacemaker function. During left ventricular
      (LV) pacing from the posterior or posterolateral coronary vein, a correctly
      positioned lead V1 registers a tall R wave and there is right axis deviation in
      the frontal plane with few exceptions. During simultaneous biventricular
      stimulation from the right ventricular (RV) apex and LV site in the coronary
      venous system, the QRS complex is often positive (dominant) in lead V1 and the
      frontal plane QRS axis usually points to the right superior quadrant and
      occasionally the left superior quadrant. The reported incidence of a dominant R
      wave in lead V1 during simultaneous biventricular pacing (RV apex) varies from
      50% to almost 100% for reasons that are not clear. During simultaneous
      biventricular pacing from the posterior or posterolateral coronary vein with the
      RV lead in the outflow tract, the paced QRS in lead V1 is often negative and the
      frontal plane paced QRS axis is often directed to the right inferior quadrant
      (right axis deviation). A negative paced QRS complex in lead V1 during
      simultaneous biventricular pacing with the RV lead at the apex can be caused by
      incorrect placement of the lead V1 electrode (too high on the chest), lack of LV
      capture, LV lead displacement, pronounced latency (true exit block), conduction
      delay around the LV stimulation site, ventricular fusion with the intrinsic QRS
      complex, coronary venous LV pacing via the middle or anterior cardiac vein,
      unintended placement of two leads in the RV and severe conduction abnormalities
      within the LV myocardium. Most of these situations can cause a QS complex in lead
      V1 which should be interpreted (excluding fusion) as reflecting RV preponderance
      in the depolarization process. Barring the above causes, a negative complex in
      lead V1 is unusual and it probably reflects a different activation of a
      heterogeneous biventricular substrate (ischemia, scar, His-Purkinje
      participation). The latter is basically a diagnosis of exclusion. With a non
      dominant R wave in lead V1, programming the V-V interval with LV preceding RV may
      bring out a diagnostic dominant R wave in lead V1 representing the contribution
      of LV stimulation to the overall depolarization process. In this situation the
      emergence of a dominant R wave confirms the diagnosis of prolonged LV latency
      (exit delay) or an LV intramyocardial conduction abnormality near the LV pacing
      site but it rules out the various causes of LV lead malfunction or misplacement.

PMID- 21947983
TI  - Coarctation of the aorta: from fetal life to adulthood.
AB  - Coarctation of the aorta was once viewed as a simple discrete narrowing of the
      aortic isthmus that could be 'cured' by surgical intervention. It is now clear
      that this condition may: (1) affect the aortic arch in a highly variable manner;
      (2) be associated with a host of other left sided heart lesions; (3) represent a
      wider vasculopathy within the pre-coarctation arterial tree, leading to
      significant prevalence of hypertension by adolescence, and subsequent risk of
      early morbidity and death. This review outlines the evaluation and treatment of
      this disease from pre-natal to adult life.

PMID- 21947984
TI  - The diagnostic and prognostic value of first hour glycogen phosphorylase
      isoenzyme BB level in acute coronary syndrome.
AB  - BACKGROUND: Evaluating patients with symptoms suggestive of acute coronary
      syndrome (ACS) is a time consuming, expensive and problematic process in the
      emergency department. This study aimed to evaluate the diagnostic and prognostic
      value of glycogen phosphorylase isoenzyme-BB (GP-BB) in ACS. METHODS: A total of
      72 patients (mean age 61.8 +/- 11.6 years) with ACS were enrolled. The ELISA
      method for determining GP-BB level was performed and considered positive at > 10
      ng/mL. Duration of angina, type of ACS, demographic features, myoglobin,
      creatinine kinase and troponin T (cTnT) were also assessed. The cTnT levels eight
      hours after pain onset was considered the gold standard test for the diagnosis of
      myocardial infarction. RESULTS: The most sensitive biomarker at first hour of
      admission was GP-BB (95.8%). However, the specificity of GP-BB was low (43.7%).
      Receiver operating characteristics curve analysis of the GP-BB level for
      predicting myocardial infarction revealed the area under the curve value as 0.82
      (SE 0.04; 95% CI 0.78-0.85). Positive treadmill exercise test (60% vs 17%, p =
      0.047), coronary artery disease (CAD; 59% vs 19%, p = 0.007), percutaneous
      coronary intervention (44% vs 27%, p = 0.031) and 30-day mortality and/or
      readmission (33% vs 5%, p = 0.028) were found to be higher in unstable angina
      (UA) patients having GP-BB (+). CONCLUSIONS: GP-BB is considerably
      cardiosensitive at the first hour of admission in patients with ACS, but the
      specificity of GP-BB is lower and it is elevated in nearly half of the patients
      with UA. However, in this group, GP-BB predicts significant CAD and the combined
      end-point of mortality and re-hospitalization.

PMID- 21947985
TI  - Use of implantable cardioverter-defibrillators for primary prevention in older
      patients: a systematic literature review and meta-analysis.
AB  - BACKGROUND: Randomized clinical trials (RCTs) have demonstrated the efficacy of
      implantable cardioverter-defibrillators (ICDs) in reducing sudden cardiac death
      (SCD) in specific patient populations. However, patients >= 65 years were under
      represented in these trials and the overall benefit of ICDs may be diminished in
      older patients due to competing risks for death. We evaluate the published data
      on ICD efficacy at reducing all-cause mortality in patients >= 65 years and in
      patients >= 75 years. METHODS: We searched MEDLINE to identify RCTs and
      observational studies of ICDs that provided age-based outcome data for primary
      prevention of SCD. The primary endpoint was mortality evaluated by a meta
      analysis of the RCTs using a random-effects model. Secondary endpoints included
      operative mortality, long-term complications and quality of life. RESULTS: The
      enrollment of patients >= 65 years in RCTs was limited (range: 33% in DEFINITE to
      56% in MUSTT). Combining data from four RCTs (n = 3,562) revealed that primary
      prevention ICD therapy is efficacious in reducing all-cause mortality in patients
      >= 65 years (HR 0.66; 95% CI 0.50-0.87; test of heterogeneity: X(2) = 5.26; p =
      0.15). For patients >= 75 years, combining data from four RCTs (n = 579) revealed
      that primary prevention ICD therapy remains efficacious in reducing all-cause
      mortality (HR 0.73; 95% CI 0.51-0.974; p = 0.03). There appears to be no
      difference in ICD-related, operative, in-hospital, or long- -term complications
      among older patients compared to younger patients, although it remains unclear if
      older patients have a better quality of life with an ICD than younger patients.
      CONCLUSIONS: Although the overall evidence regarding ICD efficacy in patients >=
      65 years is limited and divergent, and the evidence available for patients >= 75
      years is even more sparse, our meta-analysis suggests that primary prevention
      ICDs may be beneficial in older patients. Our findings need to be validated by
      future studies, particularly ones examining ICD complications and quality of
      life.

PMID- 21947986
TI  - Association between plasma levels of pigment epithelium-derived factor and renal
      dysfunction in patients with coronary artery disease.
AB  - BACKGROUND: Although plasma pigment epithelium-derived factor (PEDF) levels have
      been shown to be significantly correlated with the levels of creatinine (Cr) in
      type 2 diabetes, little is known about the association between PEDF levels and
      renal dysfunction in patients with coronary artery disease (CAD). METHODS: We
      enrolled 134 consecutive patients with diagnosed CAD and measured plasma levels
      of PEDF, serum Cr, uric acid (UA) and high-sensitive C-reactive protein (hsCRP).
      RESULTS: Plasma PEDF levels were positively correlated with serum Cr (p < 0.0001)
      and UA (p < 0.0001) and negatively correlated with the estimated glomerular
      filtration rate (eGFR) (p < 0.0001), whereas there was no association between
      plasma PEDF and age or hsCRP. When the subjects were divided into five groups (0
      4) according to the number of metabolic factors (obesity, diabetes, hypertension
      and dyslipidemia), PEDF levels in patients with four factors were significantly
      higher than those in patients without factors. Next, we divided the patients into
      quartiles according to their plasma PEDF levels (< 9.9 MUg/mL, 9.9-12.8, 12.9- 
      15.7, > 15.7). The eGFR in the first group was significantly higher than those in
      the third and fourth groups. Multivariate logistic analysis indicated that eGFR
      (p < 0.0001) and age (p = 0.030) were significant independent variables that
      correlated with the quartile classification according to PEDF levels.
      CONCLUSIONS: This study revealed that PEDF may play a role in renal dysfunction
      in CAD patients.

PMID- 21947987
TI  - Can the result of a tilt test be predicted in the first five minutes?
AB  - BACKGROUND: Head-up tilt testing (HUT) plays a pivotal role in the management of
      vasovagal syncope (VVS). Heart rate variability (HRV) is a well-known method used
      for noninvasive evaluation of autonomic nervous system activity. However,
      different results have been obtained in studies that have evaluated the HRV
      response to HUT in patients with VVS. METHODS: One hundred fourteen patients with
      recurrent VVS were enrolled in the study. According to the results of HUT,
      patients were divided into five groups: positive (n = 30) and negative (n = 23)
      Westminster; positive (n = 44) and negative (n = 11) Italian. Fourteen healthy
      volunteers with no history of syncope comprised the control group. Spectral
      indices of HRV variability were analyzed for three short-term intervals. RESULTS:
      Both protocols showed similar distribution of responses to tilt-testing. In the
      supine position, significant differences were observed between patients from
      groups 1, 2 and 3 in comparison with the control and Italian negative groups.
      They had significantly lower initial results of LF(1) [nu] and LF(1)/HF(1) ratio,
      and higher HF(1) [nu] values. The onset of HUT in patients with positive
      Westminster protocol was characterized by an almost two-fold increase in LF [nu]
      and decrease in HF [nu] compared to all other patients. LF(2)/HF(2) ratio in the
      Westminster positive group had increased more than five times since the baseline
      level, while during the last period, LF(3)/HF(3) ratio had increased more than
      six times. CONCLUSIONS: Patients with VVS have disturbed sympathovagal balance at
      rest. Our data suggests that the results of HUT could be predicted by analyzing
      the spectral parameters of HRV during the first five minutes of the test. The
      reaction to orthostasis in patients with syncope during the Westminster protocol
      was more severe compared to the Italian protocol group and the control group.
      Vasovagal response during the Italian protocol may be triggered by drug-induced
      vasodilatation.

PMID- 21947988
TI  - Clinical presentation and management of patients with hyperadrenergic postural
      orthostatic tachycardia syndrome. A single center experience.
AB  - BACKGROUND: We present our single center experience of 27 patients of
      hyperadrenergic postural orthostatic tachycardia syndrome (POTS). METHODS: In a
      retrospective analysis, we reviewed the charts of 300 POTS patients being
      followed at our autonomic center from 2003 to 2010, and found 27 patients
      eligible for inclusion in this study. POTS was defined as symptoms of orthostatic
      intolerance (of greater than six months' duration) accompanied by a heart rate
      increase of at least 30 bpm (or a rate that exceeds 120 bpm) that occurs in the
      first 10 min of upright posture or head up tilt test (HUTT) occurring in the
      absence of other chronic debilitating disorders. Patients were diagnosed as
      having the hyperadrenergic form based on an increase in their systolic blood
      pressure of >= 10 mm Hg during the HUTT (2) with concomitant tachycardia or their
      serum catecholamine levels (serum norepinephnrine level >= 600 pg/mL) upon
      standing. RESULTS: Twenty seven patients, aged 39 +/- 11 years, 24, (89%) of them
      female and 22 (82%) Caucasian were included in this study. Most of these patients
      were refractory to most of the first and second line treatments, and all were on
      multiple combinations of medications. CONCLUSIONS: Hyperadrenergic POTS should be
      identified and differentiated from neuropathic POTS. These patients are usually
      difficult to treat and there are no standardized treatment protocols known at
      this time for patients with hyperadrenergic POTS.

PMID- 21947989
TI  - Effects of levosimendan without loading dose on systolic and diastolic function
      in patients with end-stage heart failure.
AB  - BACKGROUND: Levosimendan (L) is used in clinical practice for the treatment of
      severe heart failure (HF); it has inotropic and vasodilatory effects, without
      increasing myocardial oxygen consumption. In acute HF, levosimendan improves
      hemodynamic parameters; previous studies have demonstrated that it has favorable
      effects on left ventricular (LV) diastolic function. The aim of our study was to
      evaluate the effect of on LV long-axis function that represents the earlier
      marker of diastolic dysfunction. METHODS: We enrolled 41 patients (age 62 +/- 12
      years) admitted to our Department for acute HF, NYHA class IV and severe LV
      dysfunction. Twenty-six patients were treated with L (0.1 MUg/kg/min ev for 24 h
      without loading dose) and 15 patients were treated with standard therapy (C). We
      evaluated clinical, blood exams and echocardiographic parameters at baseline and
      one week after L or C treatment. RESULTS: Baseline demographic, clinical and
      biochemical data were similar in both groups. After one week, the L group had
      shown a significant improvement in NYHA class and a reduction of pro-B-type
      natriuretic peptide (pro-BNP). In echocardiographic study, we observed an
      improvement in LV longitudinal function (p < 0.05) and LV ejection fraction (p <
      0.05) with a reduction of E/E' (p < 0.05) in the L group. We divided the L group
      into ischemic and non- -ischemic patients and we demonstrated a significant
      increase in systolic function in the former. No differences were found between
      subgroups in diastolic function. CONCLUSIONS: L therapy, without loading dose,
      improves NYHA class and ventricular function in patients with acute HF; we
      believe that these prolonged hemodynamic effects are due to active metabolities
      of L.

PMID- 21947990
TI  - Relationship between R-R interval variation and left ventricular function in
      sinus rhythm and atrial fibrillation as estimated by means of heart rate
      variability fraction.
AB  - BACKGROUND: Reduced heart rate variability (HRV) is associated with a poor
      outcome in patients with sinus rhythm (SR) or atrial fibrillation (AF). However,
      cut-off points for HRV measures differ between SR and AF. We hypothesized that a
      global index of 24-hour HRV based on evaluation of scatterplot would describe HRV
      irrespective of cardiac rhythm. METHODS: 407 patients with ischemic heart disease
      (317 male, 90 female, mean age 57 +/- 9 years) were studied. 331 patients had SR
      and 76 patients had AF. 24-hour ECGs were recorded, and standard HRV indices were
      calculated. Scatterplots was used to determine the HRV fraction (HRVF, %). HRV
      measures were compared in respect to left ventricular ejection fraction (LVEF L
      35% or > 35%). RESULTS: Standard HRV measures were higher in AF-patients despite
      the mean RR interval was lower. In patients with LVEF L 35%, standard HRV indices
      were lower in SR group, in AF group only SDNN and RMSSD were reduced. The HRVF
      was comparably reduced (SR 39.3 +/- 15.3%, AF 37.3 +/- 17.9%). In patients with
      LVEF > 35%, HRVF did not differ between SR (47.2 +/- +/- 10.5%) and AF (46.1 +/-
      12.1%). The HRVF correlated with SDNN and SDANN (~0.85) in SR. Correlations were
      weaker in AF (~0.6). Standard HRV indices and HRVF showed similar relations with
      LVEF, but only in AF at the same range. CONCLUSIONS: The HRV fraction allows for
      HRV evaluation irrespective of cardiac rhythm. The index elicited a similar
      dependence of HRV on left ventricular function in SR and AF.

PMID- 21947991
TI  - Frequency, origins and courses of anomalous coronary arteries in 607 Turkish
      children with tetralogy of Fallot.
AB  - BACKGROUND: The aim of this study was to investigate the incidence, origins and
      courses of coronary artery anomalies using a combination of angiographic and
      surgical methods in Turkish children with tetralogy of Fallot (ToF). METHODS:
      Seventy-seven patients in whom coronary artery anomalies had been identified by
      angiography and/or at operation out of 549 ToF and 58 Fallot-type double outlet
      right ventricle (total 607) patients, were enrolled in the study. RESULTS:
      Coronary artery anomalies were identified in 12.7% of the patients. The incidence
      was 12.2% (67/549) in patients with aortic overriding 50%, and 17.2% (10/58) with
      aortic overriding > 50% (p > 0.05). The incidence of anomalous coronary arteries
      crossing the right ventricular outflow tract (RVOT) was 7.91%. The commonest
      anomaly was the left anterior descending artery (LAD) or accessory LAD arising
      from the right coronary artery (RCA; n = 25). Other frequent anomalies were
      single coronary ostium (n = 21) and enlarged conal branch of RCA (n = 18). In
      62.3% (48/77) of the patients with a coronary anomaly, the anomalous vessels were
      crossing the RVOT. The ratio of crossing the RVOT was 92.0% for LAD arising from
      the RCA, 66.7% for conal branch, and 42.9% for single coronary ostium.
      CONCLUSIONS: Two thirds of the anomalous coronary arteries were crossing the
      RVOT, and had surgical importance. The most frequent coronary artery anomaly that
      crossed the RVOT was the LAD or the accessory LAD arising from the RCA. Also, an
      enlarged conus artery should be considered as an anomaly because of its surgical
      importance, given its high rate of crossing the RVOT.

PMID- 21947992
TI  - Acute myocarditis mimicking acute myocardial infarction associated with pandemic
      2009 (H1N1) influenza A virus.
AB  - The prevalence of myocardial involvement in influenza infection ranges from 0% to
      11% depending on the diagnostic criteria used to define myocarditis. Whether such
      an association holds for the novel influenza A strain, pandemic-2009-H1N1,
      remains unknown. The clinical presentation of myocarditis varies and often mimics
      myocardial infarction. Although history, physical examination, laboratory data
      points, and electrocardiogram are helpful in distinguishing myocarditis from
      myocardial infarction, differential diagnosis can sometimes be difficult. Here,
      we present the first known report of acute myocarditis mimicking acute myocardial
      infarction associated with the pandemic influenza A virus (H1N1) infection.

PMID- 21947993
TI  - Aneurysmal coronary arteriovenous fistula closing with covered stent deployment:
      a case report and review of literature.
AB  - Coronary arteriovenous fistula (CAVF) is a rarely encountered congenital coronary
      anomaly, in which coronary artery blood flow bypasses the myocardial capillary
      network and usually drains to a heart chamber or great vessel. It is usually
      asymptomatic. However, the risk of symptoms and complications increases with age.
      High output heart failure, pulmonary hypertension, myocardial ischemia and
      infective endocarditis may complicate the course of this anomaly. The appearance,
      and even rupture, of a saccular aneurysm is one of the even rarer complications
      of CAVF. Here we describe a 57 year-old patient with incidental finding of an
      aneurysmal CAVF which was treated successfully using covered stent.

PMID- 21947994
TI  - Right atrial tuberculoma: a diagnosis too late.
AB  - Solitary intra-cardiac cavity tuberculoma is extremely rare and often only
      diagnosed during a post-mortem. We report a case of right atrial tuberculoma
      causing right atrial outflow tract obstruction in an immune-compromised man. The
      diagnosis of cardiac tuberculoma was made through the detection of mycobacterium
      tuberculosis DNA by tuberculosis-polymerase chain reaction in the pericardial
      fluid. The patient succumbed five days after admission but an autopsy was refused
      by his family.

PMID- 21947995
TI  - Tako-tsubo cardiomyopathy precipitated by pheochromocytoma crisis.
AB  - We report the case of a 69 year-old Chinese lady with pheochromocytoma who
      developed chest pain and acute ST-segment elevation in the anterior leads on
      electrocardiography. She was given intravenous phenoxybenzamine for alpha
      blockade before undergoing urgent coronary angiography. This revealed minor
      coronary artery disease. Left ventriculogram demonstrated akinesis in the apex
      with hypercontraction of the basal segments. The Tako-tsubo cardiomyopathy
      eventually resolved with surgical removal of the pheochromocytoma. This case
      highlights the challenging management of suspected acute myocardial infarction in
      pheochromocytoma crisis and also reinforces the notion that Tako-tsubo
      cardiomyopathy is likely precipitated by catecholamine excess.

PMID- 21947996
TI  - Interrupted aorta in mosaic Turner syndrome.

PMID- 21947997
TI  - Committed function for the first delivered shock of an uncommitted implantable
      cardioverter-defibrillator.

PMID- 21947998
TI  - Tachycardia-induced cardiomyopathy caused by a special pacemaker algorithm.
AB  - An elderly lady presented with breathlessness, fever and palpitations. She was
      treated for community-acquired pneumonia with antibiotics. Subsequently, she went
      into acute pulmonary edema. She was managed with standard heart failure
      medications and a trial of noninvasive ventilation. ECG showed A-V sequential
      pacing at a rate of 150/min with broad QRS. It was thought to be a pacemaker
      related tachycardia. On pacemaker check, a special algorithm (atrial fibrillation
      suppression algorithm) was switched off. She subsequently improved. We here
      review the cause of this tachycardia-induced cardiomyoapthy.

PMID- 21947999
TI  - Continuity equation is the echocardiographic method of choice to assess
      degenerative mitral stenosis.
AB  - We present a rare case of a patient with severe, symptomatic degenerative
      calcific mitral stenosis (MS). Calcification of mitral valve annulus (MVA) is a
      frequent finding in elderly patients. It can be isolated or associated more often
      with mitral valve insufficiency than MS. In rare cases, it results in severe MS.
      An accurate measurement of MVA in degenerative calcific MS is problematic because
      the limiting orifice is near the annulus and not at the leaflet tips as in
      rheumatic MS. Continuity equation is the best echocardiographic method to assess
      the MVA in degenerative MS, correlating well with invasive methods. Real-time
      three-dimensional echocardiography is a promising tool and provides an accurate
      measurement of MVA in calcific MS, with a very good correlation compared to
      continuity equation. On the other hand, the use of pressure half-time is often
      inaccurate and should be avoided, while two-dimensional planimetry is difficult
      and not reliable in degenerative MS. The values of mean gradient and systolic
      pulmonary artery pressure depend on several factors and should be only supportive
      signs and should not be considered as surrogate markers of the severity of MS.

PMID- 21948000
TI  - 500(th) anniversary of the birth of the precursor of modern cardiology: Josephus
      Struthius Polonus (1510-1568).
AB  - In this article, the authors take a closer look at the figure of Josephus
      Struthius Polonus (1510- -1568), one of the most famous physicians of the
      European Renaissance, on the 500(th) anniversary of his birth. Struthius became
      famous for his critical analysis of Galen's works and his own research into the
      circulatory system. The analysis of Struthius's scientific achievements leads to
      a conclusion that he was one of the pioneers of modern cardiology. He was a
      precursor of William Harvey (1578-1657) in studying the cardiovascular system,
      and the first person in the history of European medicine to present the pulse in
      a graphic form. He also presented similar ideas to those proposed in the 19(th)
      century by the inventor of the sphygmograph Karl von Vierodt (1818-1884), and the
      inventor of the polygraph Sir James Mackenzie (1853-1925).

PMID- 21948002
TI  - History of Swine influenza viruses in Asia.
AB  - The pig is one of the main hosts of influenza A viruses and plays important roles
      in shaping the current influenza ecology. The occurrence of the 2009 H1N1
      pandemic influenza virus demonstrated that pigs could independently facilitate
      the genesis of a pandemic influenza strain. Genetic analyses revealed that this
      virus was derived by reassortment between at least two parent swine influenza
      viruses (SIV), from the northern American triple reassortant H1N2 (TR) and
      European avian-like H1N1 (EA) lineages. The movement of live pigs between
      different continents and subsequent virus establishment are preconditions for
      such a reassortment event to occur. Asia, especially China, has the largest human
      and pig populations in the world, and seems to be the only region frequently
      importing pigs from other continents. Virological surveillance revealed that not
      only classical swine H1N1 (CS), and human-origin H3N2 viruses circulated, but all
      of the EA, TR and their reassortant variants were introduced into and co
      circulated in pigs in this region. Understanding the long-term evolution and
      history of SIV in Asia would provide insights into the emergence of influenza
      viruses with epidemic potential in swine and humans.

PMID- 21948003
TI  - The screens culture: impact on ADHD.
AB  - Children's use of electronic media, including Internet and video gaming, has
      increased dramatically to an average in the general population of roughly 3 h per
      day. Some children cannot control their Internet use leading to increasing
      research on "internet addiction." The objective of this article is to review the
      research on ADHD as a risk factor for Internet addiction and gaming, its
      complications, and what research and methodological questions remain to be
      addressed. The literature search was done in PubMed and Psychinfo, as well as by
      hand. Previous research has demonstrated rates of Internet addiction as high as
      25% in the population and that it is addiction more than time of use that is best
      correlated with psychopathology. Various studies confirm that psychiatric
      disorders, and ADHD in particular, are associated with overuse, with severity of
      ADHD specifically correlated with the amount of use. ADHD children may be
      vulnerable since these games operate in brief segments that are not attention
      demanding. In addition, they offer immediate rewards with a strong incentive to
      increase the reward by trying the next level. The time spent on these games may
      also exacerbate ADHD symptoms, if not directly then through the loss of time
      spent on more developmentally challenging tasks. While this is a major issue for
      many parents, there is no empirical research on effective treatment. Internet and
      off-line gaming overuse and addiction are serious concerns for ADHD youth.
      Research is limited by the lack of measures for youth or parents, studies of
      children at risk, and studies of impact and treatment.

PMID- 21948004
TI  - Phylogenetic and structural analysis of HCV nonstructural protein 4A from
      Pakistani patients.
AB  - Hepatitis C virus nonstructural protein, NS4A, is a small protein comprising of
      about 54 amino acids. Despite its small size, it plays key role in many viral and
      cellular functions. The most important of which is its role as the co-factor of
      viral serine protease and helicase (NS3). Our study examines the phylogenetic and
      structural analysis of this coding region after isolation from Pakistani HCV
      patient samples. Phylogenetic analysis of the gene revealed that Pakistani 3a HCV
      strains do not show significant divergence from those reported from the rest of
      the world. The findings of this study also depict that NS4A sequence is conserved
      within genotypes, whereas it shows variations among different genotypes. While
      predicting the tertiary structure of the protein two important mutations (H28Y &
      E32G) were observed when comparing the Pakistani sequences with that of a
      reference HCV (genotype 3a) strain NZL (D17763). These mutations were observed in
      the central domain of NS4A which is responsible for interaction with NS3. Taken
      together, these mutations within the NS4A coding region can play an  important
      role in the binding capacity of NS4A with HCV serine protease NS3.

PMID- 21948005
TI  - The Citrus leaf blotch virus movement protein acts as silencing suppressor.
AB  - To counteract plant antiviral defense based on RNA silencing, many viruses
      express proteins that inhibit this mechanism at different levels. The genome of
      Citrus leaf blotch virus (CLBV) encodes a 227-kDa protein involved in
      replication, a 40-kDa movement protein (MP), and a 41-kDa coat protein (CP). To
      determine if any of these proteins might have RNA silencing suppressor
      activities, we have used Agrobacterium-mediated transient assays in the green
      fluorescent protein (GFP)-expressing Nicotiana benthamiana line 16c. Only CLBV MP
      was able to suppress intracellular GFP silencing induced by expression of either
      single- or double-stranded (ds) GFP RNA, but not cell-to-cell or long distance
      spread of the silencing signal. The MP suppressor activity was weak compared to
      other characterized viral suppressor proteins. Overall our data indicate that MP
      acts as a suppressor of local silencing probably by interfering in the silencing
      pathway downstream of the steps of dsRNA and small RNAs generation.

PMID- 21948006
TI  - Complete nucleotide sequence analysis of a Korean strain of hepatopancreatic
      parvovirus (HPV) from Fenneropenaeus chinensis.
AB  - Hepatopancreatic parvovirus (HPV) of shrimp is distributed worldwide and the
      entire genome of Thailand and Indian strains (PmDNV) and one Australian strain
      (PmergDNV) have now been reported. The complete nucleotide sequence of a HPV
      strain isolated from the fleshy prawn Fenneropenaeus chinensis in Korea (FcDNV)
      was determined and compared to previously reported sequences. The entire genome
      of FcDNV contains 6,336 nucleotides, with 40% G+C content, which is the biggest
      of the known HPV strains. The HPV genome has three open reading frames (ORFs)
      with a slight overlap between the first and second ORFs. The three ORFs encode
      the NS2 and NS1 proteins and VP that consist of 425, 578, and 820 amino acids,
      respectively. Among the three proteins, the NS1 protein shows the highest
      sequence similarity to the NS1 protein of other known HPV strains, followed by
      the NS2 protein and the VP protein. Phylogenetic analyses showed that HPV can be
      grouped into three genotypes, as previously reported, and FcDNV can be grouped as
      genotype I, with HPV strains isolated in Madagascar and Tanzania. The nucleotide
      sequences of the noncoding regions at the 5'- and 3'-ends of the plus-strand
      genome showed a Y-shaped hairpin structure and simple hairpin structure,
      respectively.

PMID- 21948007
TI  - Molecular characterization and specific detection of two genetically
      distinguishable strains of East Asian Passiflora virus (EAPV) and their
      distribution in southern Japan.
AB  - The Ibusuki (IB) strain of the East Asian Passiflora virus (EAPV) causes mottling
      of fruit when it infects passionfruit, but not malformation or woodiness, unlike
      the Amami-O-shima (AO) strain, and the host range for these two strains are
      different. We determined the complete nucleotide sequence of the IB strain, and a
      comparison with that of the AO strain revealed the great diversity of the 5'
      terminal region of the IB strain's genome (5' UTR and P1 gene). The involvement
      of these regions in the different symptoms on fruit and host range was suggested.
      The neighbor-joining tree constructed using the nucleotide sequences of coat
      protein gene of eight EAPV isolates including those from abroad showed the
      independent position of the IB strain, and that constructed using the whole ORFs
      also showed distant relationships between the AO and IB strains. We investigated
      the distribution of the two strains in southern Japan from 2005 to 2010. The AO
      strain was detected in the samples from AO at all periods, and its emergence was
      also observed in the Kagoshima mainland in 2005. In contrast, the IB strain is
      restricted to the Kagoshima mainland, and the distribution survey revealed that
      this strain is now extinct even in this region, indicating the uniqueness of the
      IB strain in terms of sequence properties and geographical distribution.

PMID- 21948008
TI  - [Restless legs syndrome in patients with high serum ferritin and normal iron
      levels].
AB  - AIM: To document the association between restless legs syndrome (RLS) and high
      ferritin levels in five patients. PATIENTS AND METHODS: The five patients were
      male, mean age: 59 years (range: 36-73 years). The patients were referred for RLS
      (two of them blood donors), in two cases associated with obstructive sleep apnea.
      Patients underwent a video-PSG recording. Serum iron and serum ferritin were
      determined. RESULTS: All patients fulfilled the clinical criteria for RLS: leg
      paresthesias associated with an urge to move, motor restless-ness, worsening of
      symptoms during the evening and night, and partial relief with activity,
      difficulty falling asleep, and presence of nocturnal awakenings due to RLS.
      Neurological examination, EEGs, EMGs and MRIs were normal. Video-PSGs recordings
      showed a disturbed and fragmented sleep with a reduction in total sleep time, low
      sleep efficiency, respiratory abnormalities with an apnea-hipopnea index > 10/h
      in two cases, and in all of them a periodic leg movements index > 5/h. The serum
      iron levels were within the normal range in all cases, whereas those in serum
      ferritin levels were high. CONCLUSIONS: To our knowledge the association of
      normal serum iron with high serum ferritin levels in patients diagnosed
      clinically and polygraphically as having RLS with periodic leg movements has not
      been described before. The notion of an involvement of a dopaminergic mechanism
      in the pathophysiology of RLS is supported by the decrease in the values of serum
      ferritin concentration observed in one patient during follow-up while being
      treated with dopaminergic agents.

PMID- 21948009
TI  - [Tumours of the nerve root sheath in the spine].
AB  - INTRODUCTION: Spinal schwannomas account for about 30% of intradural spinal cord
      tumors in adults. More are solitary tumors, which can occur throughout the spinal
      canal. The multiple form of neurofibromas is known as von Recklinghausen disease.
      AIM. To analyze clinical and radiologic characteristics, treatment and evolution
      of patients with spinal nerve sheath tumor. PATIENTS AND METHODS: This was a
      retrospective study in a series of patients treated surgically of spinal
      schwannomas during 25 years. The following variables were evaluated: gender, age,
      symptomatology, radiological findings, localization, surgical findings and
      results. RESULTS: We treated 35 male and 33 female with a mean age of 55 years
      (range: 12-76 years).The most common pre-surgical symptom was local or radicular
      pain in 55 patients (80.8%). In 49 cases (66.2%), the tumor was sited in the
      lumbosacral, in 15 cases (20.2%) in the dorsal tract, and in 10 cases (13.6%) in
      the cervical tract. Total removal was achieved in 70 cases (94.5%) and subtotal
      resection in 4 (5.5%). 66 tumors (89.1%) were schwannomas and the other 8 cases
      (10.9%) neurofibromas. CONCLUSIONS: Tumors of the spinal root sheaths can occur
      at any level of the spinal canal. Most patients present with local and/or
      radicular pain and in most cases total resection its possible with good
      functional recovery.

PMID- 21948010
TI  - [Diabetes mellitus as a risk factor for dementia in the Mexican elder
      population].
AB  - INTRODUCTION: Diabetes and dementia are growing problems throughout the world and
      especially in developing countries. AIM: To determine the risk of developing
      dementia in subjects with type 2 diabetes mellitus. PATIENTS AND METHODS:
      Diabetic elders free of dementia from the Mexican Health and Aging study, a
      prospective community-based cohort research were followed after two years. Socio
      demographic factors, comorbid conditions and type of diabetes treatment were
      analyzed in subjects who become demented. RESULTS: At baseline, 749 participants
      (13.8%) had diabetes mellitus. During the follow-up period (mean: 2.02 years;
      range: 1-3 years), 306 of 749 persons with diabetes mellitus developed dementia,
      yielding a relative risk (RR) of 2.08 (95% confidence interval, 95% CI = 1.59
      2.73). The effect was strongest in persons aged 80 years or older with a RR of
      2.44 (95% CI = 1.46-4.08), men had a greater relative risk than women (RR = 2.25;
      95% CI = 1.46-3.49 vs. RR = 1.98; 95% CI = 1.08-1.11) and subjects with low
      education (< 7 years of schooling) had a significant RR while those with higher
      education didn't. Individuals treated with insulin where at highest risk of
      dementia (RR = 2.83; 95% CI = 1.58-5.06). Hypertension (RR = 2.75; 95% CI = 1.86
      4.06) and depression (RR = 3.78; 95% CI = 2.37-6.04) where the two comorbidities
      which increased the risk of dementia. CONCLUSIONS: Subjects with diabetes
      mellitus have an increased risk of developing dementia. Sociodemographic factors
      and other co-morbidities highly prevalent in the Mexican population contribute to
      the diabetes-dementia association.

PMID- 21948011
TI  - [Health among persons with intellectual disability in Spain:  the European POMONA
      II study].
AB  - INTRODUCTION: International studies show that both the pattern of health and the
      healthcare provided for persons with intellectual disability (ID) and the general
      population are different. AIMS: To obtain data about the state of health of
      persons with ID and to compare them with data about the general population.
      PATIENTS AND METHODS: The P15 set of health indicators was used in a sample of
      111 subjects with ID. The health data that were found were compared according to
      the subjects' type of residence and the 2006 National Health Survey was used to
      compare these data with those for the general population. RESULTS; The sample
      with ID presented 25 times more cases of epilepsy and twice as many cases of
      obesity. Twenty per cent presented pain in the mouth and the presence of sensory
      and mobility problems, as well as psychosis, was high. We also found, however, a
      low presence of pathologies like diabetes, hypertension, osteoarthritis and
      osteoporosis. They also displayed a lower rate of participation in prevention and
      health promotion programmes, a higher number of hospital admissions and a lower
      usage of emergency services. CONCLUSIONS: The pattern of health of persons with
      ID differs from that of the general population, and they use healthcare services
      differently. It is important to develop programmes of health promotion and
      professional training that are specifically designed to attend to the needs of
      persons with ID. Likewise, it is also necessary to implement health surveys that
      include data about this population.

PMID- 21948012
TI  - [Neurology of laughter and humour: pathological laughing and crying].
AB  - INTRODUCTION: Laughter, which is usually a healthy biological phenomenon, may be
      also a symptom of several severe brain pathologies. AIM: To review the
      neurobiological bases of laughter and humour, as well as those of pathological
      laughing and crying syndrome. DEVELOPMENT: At the mesencephalic-pontine junction
      there is a central coordinator of the nuclei that innervate the muscles involved
      in laughter (facial expression, respiratory and phonatory). This centre receives
      connections from three systems: inhibitory (pre-motor and motor cortex),
      excitatory (temporal cortex, amygdala, hypothalamus) and modulator (cerebellum).
      Humour is a complex phenomenon with a range of components: the perception of the
      unexpected incongruence (occipitotemporal area, prefrontal cortex), emotional
      (reward circuit) and volitional (temporal and frontal cortex). Functional
      magnetic resonance imaging studies do not reveal a markedly prominent role of the
      right frontal lobe in processing humour, as had been suggested in the classical
      studies. The causes of pathological laughing and crying syndrome can be
      classified in two groups: altered behaviour with unmotivated happiness (Angelman
      syndrome, schizophrenia, manias, dementia) and interference with the
      inhibitory/excitatory mechanisms (gelastic epilepsy, fou rire prodromique in
      strokes, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease
      and Parkinson-plus, traumatic injuries, tumours). Serotonin and noradrenalin
      reuptake inhibitors, levodopa, lamotrigine and the association of
      dextromethorphan/quinidine can be effective in certain cases of pathological
      laughing and crying. CONCLUSIONS: As human neurobiological phenomena, laughter
      and humour also belong to the field of clinical neurology; their processing is
      affected in a number of different diseases and, in certain cases, effective
      treatment can be established.

PMID- 21948013
TI  - [Prepulse inhibition of the startle response/reflex in neuropsychiatric
      disorders].
AB  - INTRODUCTION: Prepulse inhibition (PPI) of startle is an operational measure of
      the pre-attentive filtering process known as sensorimotor gating. PPI occurs when
      a relatively weak sensory event (the prepulse) is presented 30-500 ms before a
      strong startle inducing stimulus, and reduces the magnitude of the startle
      response. This experimental paradigm has been studied in laboratory animal as
      well as in patients with schizophrenia. Recently, PPI deficits have been observed
      in other psychiatric disorders that shared some deficit in cognitive and
      sensorimotor gating. DEVELOPMENT: We have reviewed studies examining prepulse
      inhibition in humans across some neuropsychiatric disorders for asses the
      clinical and neurobiological implications of this paradigm. CONCLUSIONS: PPI
      deficits have been observed in multiple psychiatric disorders many of which
      present a common correlate anatomic-functional and a dysfunction in several
      neurotransmission systems, mainly dopamine system. These dysfunctions are
      independent of categorical diagnostic and they have proposed as a biological
      marker of vulnerability for some psychiatric disorders.

PMID- 21948015
TI  - [Plasmapheresis in a paediatric patient with transverse myelitis and Guillain
      Barre syndrome secondary to infection by Mycoplasma pneumoniae].

PMID- 21948016
TI  - [Frontal lobe nocturnal epilepsy in an adult with Gilles de la Tourette
      syndrome].

PMID- 21948018
TI  - Complete genome characterization of a East European Type 1 subtype 3 porcine
      reproductive and respiratory syndrome virus.
AB  - Porcine reproductive and respiratory syndrome (PRRS) is a swine disease of major
      economic importance that causes reproductive and respiratory problems in pigs.
      PRRSV strains are divided into European (Type 1) and North-American (Type 2)
      genotypes. Within the European PRRSV genotype, three subtypes have been
      delineated. Full genome sequences for North American and European subtype 1
      strains have been described. Here, the first complete genomic characterization of
      a European subtype 3 strain (Lena) is described. Amplification of Orf1a and Orf1b
      fragments was achieved using a set of degenerate oligonucleotides. Using RT-PCR
      with Lena-specific primers, the full length sequence (15001 nt) was obtained.
      Alignment of Lena with European subtype 1 reference strain Lelystad showed
      variation over the entire length (84% identity/89% similarity at amino acid
      level) with the most variation in Orf1a (Nsp2/NSP2) with a deletion of 29 amino
      acids. Phylogenetic relationships using different Orfs supported Lena's genetic
      distinction from European subtype 1 strains. The availability of the European
      subtype 3 PRRSV full genome may be important for the understanding of PRRSV
      evolution and the more pronounced pathogenic nature of Lena.

PMID- 21948019
TI  - Creatine affects in vitro electrophysiological maturation of neuroblasts and
      protects them from oxidative stress.
AB  - Creatine (Cr) is a very popular ergogenic molecule that has recently been shown
      to have antioxidant properties. The effectiveness of Cr supplementation in
      treating neurological diseases and Cr deficiency syndromes has been demonstrated,
      and experimental reports suggest that it plays an important role in CNS
      development. In spite of this body of evidence, the role of Cr in functional and
      structural neuronal differentiation is still poorly understood. Here we used
      electrophysiological, morphological, and biochemical approaches to study the
      effects of Cr supplementation on in vitro differentiation of spinal neuroblasts
      under standard conditions or subjected to oxidative stress, a status closely
      related to perinatal hypoxia-ischemia, a severe condition for developing brain.
      Cr supplementation (10 and 20 mM) completely prevented the viability decrease and
      neurite development impairment induced by radical attack, as well as nonprotein
      sulphydryl antioxidant pool depletion. Similar results were obtained using the
      antioxidant trolox. Furthermore, Cr supplementation induced a significant and
      dose-dependent anticipation of Na(+) and K(+) current expression during the
      period of in vitro network building. Consistently with the latter finding, higher
      excitability, expressed as number of spikes following depolarization, was found
      in supplemented neuroblasts. All effects were dependent on the cytosolic fraction
      of Cr, as shown using a membrane Cr-transporter blocker. Our results indicate
      that Cr protects differentiating neuroblasts against oxidative insults and,
      moreover, affects their in vitro electrophysiological maturation, suggesting
      possibly relevant effects of dietary Cr supplementation on developing CNS.

PMID- 21948020
TI  - Bridging therapy for early surgery in patients on dual antiplatelet therapy after
      drug-eluting stent implantation.
AB  - OBJECTIVES: To evaluate stent-related adverse cardiac events and bleeding
      complications within 30 days after surgical procedures in patients with recent
      drug-eluting stent (DES) implantation, in whom a bridging protocol was used.
      METHODS: In our centre a bridging protocol is used in patients scheduled for
      cardiac or non-cardiac surgery within 6 months after PCI with DES implantation.
      Clopidogrel and in some cases also acetylsalicylic acid is discontinued 5 days
      prior to the planned intervention and patients are admitted 2 to 3 days before
      the intervention for tirofiban infusion. This is discontinued 4 h before
      intervention. Close postoperative monitoring is performed and double antiplatelet
      therapy is restarted as soon as possible. Thirty-six consecutive patients were
      included in the protocol, 15 receiving coronary artery bypass graft and 21 non
      cardiac interventions. Thrombotic and bleeding complications were studied for up
      to 30 days after the bridged procedure. RESULTS: No incidences of stent
      thrombosis or other adverse cardiac events (mortality, myocardial infarction)
      were seen in up to 30 days of follow-up. However, 6 bleeding events were reported
      of which 5 required a blood transfusion. CONCLUSION: Our bridging protocol in
      patients requiring surgery after recent PCI with DES seems adequate to prevent
      stent thrombosis in this high-risk group. The bleeding risk is not insignificant
      but in our patient group controllable without major late sequelae. Larger studies
      should be performed to establish safety and efficacy in order to develop
      guidelines for these patients.

PMID- 21948021
TI  - Percutaneous treatment of native aortic coarctation in adults.
AB  - Aortic coarctation is a common congenital cardiac defect, which can be diagnosed
      over a wide range of ages and with varying degrees of severity. We present two
      cases of patients diagnosed with aortic coarctation in adulthood. Both patients
      were treated by an endovascular approach. These cases demonstrate the variety of
      indications in which percutaneous treatment is an excellent alternative for
      surgical treatment in adult native coarctation patients.

PMID- 21948023
TI  - Evaluation of corneal pachymetry measurements by Galilei dual Scheimpflug camera.
AB  - PURPOSE: We present an evaluation of corneal pachymetry measurements by Galilei
      dual Scheimpflug camera by comparing central corneal thickness measured by
      Galilei with Orbscan II and ultrasonic pachymetry. SETTING: Ophthalmic Research
      Center, Shahid Beheshti University of Medical Sciences and Negah Eye Center,
      Tehran, Iran. MATERIALS AND METHODS: Central corneal thickness (CCT) was measured
      in 184 eyes of 92 healthy subjects using Galilei, Orbscan II, and ultrasonic (US)
      pachymetry. Considered as a benchmark, the measurements by US pachymetry were
      compared with those measured by the other 2 systems. RESULTS: Mean CCT was 544.4
      +/- 33.4 um, 546.7 +/- 37.9 um, and 555.8 +/- 29.6 um as measured by US
      pachymetry, Orbscan II, and Galilei systems, respectively. The mean difference of
      readings measured by US pachymetry with those measured by Orbscan II (acoustic
      coefficient 0.96) and Galilei were 2.3 um and 10.2 um, respectively. In spite of
      this discrepancy, the Galilei system had better agreement with US pachymetry than
      Orbscan II and US pachymetry (correlation coefficient 0.947 vs 0.817) and
      considering 0.98 as acoustic coefficient for Galilei CCT reading, makes its
      measurements identical to ultrasound pachymetry. CONCLUSIONS: Galilei
      measurements of CCT are well correlated with ultrasound pachymetry in normal
      eyes. After considering an acoustic coefficient equal to 0.98 for Galilei, its
      measurements will become equal to ultrasound values.

PMID- 21948024
TI  - Susceptibility to exudative age-related macular degeneration and three genetic
      polymorphisms of glutathione S-transferase Z1 (GSTZ1).
AB  - PURPOSE: To investigate whether genetic polymorphisms of GSTZ1 contribute to the
      development of exudative age-related macular degeneration (AMD). METHODS: The
      present case-control study consisted of 112 patients (44 female, 68 male) with
      exudative AMD and 112 sex frequency-matched healthy controls were randomly
      selected from unrelated volunteers in the same clinic. Genotypes were determined
      by polymerase chain reaction-restriction fragment length polymorphism-based
      method. RESULTS: There was no significant association between study polymorphisms
      and susceptibility to exudative AMD. Considering the significant difference in
      age distribution between cases and controls, age was used as a covariate in
      further analysis. After odds ratio adjustment for age, the same results were
      observed. The study polymorphisms showed linkage disequilibrium. Analysis
      revealed that there was no difference between cases and controls for the
      prevalence of the haplotypes of GSTZ1. CONCLUSIONS: Our study did not support any
      association between susceptibility to exudative AMD and polymorphisms of GSTZ1.

PMID- 21948025
TI  - Continuous glucose monitoring and retinopathy of prematurity.
AB  - PURPOSE: To use the continuous glucose monitoring system (CGMS) in very low
      birthweight (VLBW) infants to further explore the association between elevated
      glucose levels and retinopathy of prematurity (ROP) and to find new preventive
      strategies for ROP. METHODS: A secondary analysis of risk factors for ROP in VLBW
      infants was performed in the neonatal intensive care units of University Hospital
      Leuven and ZOL Genk, Belgium. The subjects were part of the NIRTURE trial
      (ISRCTN78428828). Only control subjects with conclusive ROP assessments who
      received standard clinical care were included in this analysis. A total of 100
      VLBW infants (birthweight = 1500 g) were included. Twenty-three (23%) infants
      developed ROP; 77 (77%) did not. RESULTS: Development of ROP was linked to the
      known classic risk factors. In addition, ROP was associated with higher glycemia
      levels across the first week (p between 0.01 and <0.0001). Across the first week,
      glycemia predicted ROP with receiver operating characteristic (ROC) scores
      between 0.67 and 0.80, and with a median glycemia cutoff of 6.7 mmol/L.
      Comparison of ROC curves revealed first-week glycemia as an important variable in
      the development of ROP with a predictive power as high as the classic risk
      factors. CONCLUSIONS: Moderately elevated glucose levels in the first week of
      life are associated with the development of ROP. They contribute to this
      multifactorial disease in a way equal to the known classical risk factors for
      ROP. Therefore, careful monitoring of glucose levels by CGMS can be helpful in
      the prevention of ROP.

PMID- 21948026
TI  - Spontaneous dislocation of in-the-bag intraocular lens primarily in cases with
      prior vitrectomy.
AB  - PURPOSE: To report cases of late onset spontaneous in-the-bag dislocation of the
      intraocular lens (IOL) and to compare these results with past reports. METHODS:
      We retrospectively studied 21 eyes of 18 patients with dislocation of the entire
      capsular bag containing the IOL. Gender, age, interval between original surgery
      and IOL dislocation, and the predisposing factors were examined. Cases occurring
      after trauma were excluded. RESULTS: The mean +/- SD age of the 12 men (57.1%)
      and 9 women included in the study was 67.8 +/- 8.6 years at the time of the IOL
      removal procedure. The interval between the original surgery and the IOL
      dislocation was 7.9 +/- 8.6. Associated clinical conditions included vitrectomy
      in 8 eyes (40.0%) of 7 patients, high myopia in 3 eyes (14%) of 2 patients,
      uveitis in 2 eyes (9.5%) of 2 patients, retinitis pigmentosa in 2 eyes (9.5%) of
      1 patient, and pseudoexfoliation in 1 eye (4.8%) of 1 patient. There was no
      identifiable associated condition in 2 eyes (9.5%) of 2 patients, who were
      comparatively younger than the other cases. This result differs from previously
      published reports that have found a higher frequency of pseudoexfoliation and
      lower frequency of prior vitrectomy. CONCLUSIONS: In-the-bag IOL dislocation was
      frequently associated with prior vitrectomy and sometimes occurred without
      specific conditions.

PMID- 21948027
TI  - Endoscopic dacryocystorhinostomy not using canalicular silicone intubation tube
      with and without mitomycin C: a comparative study.
AB  - PURPOSE: To determine the outcome and safety of endoscopic dacryocystorhinostomy
      (EN-DCR) with the use of adjunctive mitomycin C (MMC) in nasolacrimal duct
      obstruction in adults. METHODS: In this retrospective, comparative case series,
      54 consecutive adult patients underwent EN-DCR. We performed endonasal
      dacryocystorhinostomy with adjunctive MMC in 28 patients and endonasal
      dacryocystorhinostomy without MMC in 26 patients. All patients underwent a
      standardized procedure, with an endonasal approach to the lacrimal sac, surgical
      removal of nasal mucosa, lacrimal bone, and a fragment of the frontal process of
      the maxilla. The medial wall of the lacrimal sac was removed completely. In the
      study group (28 patients), a neurosurgical cottonoid soaked in MMC at 0.5 mg/mL
      was placed at the osteotomy site for 5 minutes (not using canalicular silicone
      intubation tube). In the other group (26 patients), standard endonasal
      dacryocystorhinostomy technique was used without MMC (not using canalicular
      silicone intubation tube). Main outcome measures were resolution of epiphora,
      absence of discharge, and patency of the ostium confirmed by irrigation at 6
      months. RESULTS: The EN-DCR procedure with adjunctive MMC was successful in 24
      (85.71%) cases. The mean follow-up was 14.3 months (8-24 months). No significant
      complications were encountered. In the control group, the EN-DCR was successful
      in 19 patients (73.07%). The mean follow-up was 13.2 months (6-24 months).
      CONCLUSIONS: Endoscopic dacryocystorhinostomy with MMC is a safe and successful
      procedure for the treatment of nasolacrimal duct obstruction in adults.

PMID- 21948028
TI  - Microtubule-associated protein 2, an early blood marker of ischemic brain injury.
AB  - The aim of this study was to develop a sensitive and rapid blood marker to detect
      ischemic brain injury, because imaging techniques have a limited capacity to
      identify lesions during the first crucial hours without massive tissue
      destruction. Rats were subjected to middle cerebral artery occlusion for various
      durations (0.5-3 hr), followed by reperfusion. At different time points after
      ischemia and/or ischemia-reperfusion, the amounts of glial fibrillary acidic
      protein (GFAP) and microtubule-associated protein 2 (MAP2) in the cerebrospinal
      fluid (CSF) and serum were analyzed by Western blotting. Brain infarction was
      observed in an ischemia-duration-dependent manner. GFAP was drastically increased
      in the CSF 24 and 48 hr after reperfusion, without change in the serum level.
      Serum levels of MAP2 remarkably increased as early as 0.5 hr of ischemia, much
      earlier than the observation of minimal tissue injury 3 hr following occlusion.
      The serum MAP2 level was further increased by a short period (2 hr) of
      reperfusion, even in 0.5- and 1-hr ischemic rats, despite not observing any
      typical tissue injuries 24 hr after reperfusion. These results indicate that the
      MAP2 protein may be able to detect early neuronal injuries, because the level of
      this protein in the blood spikes before the appearance of visible macrolesions.
      Therefore, MAP2 could potentially be used as a novel early marker for the
      detection of a neurotoxic insult.

PMID- 21948029
TI  - Femoral neck narrowing following hip resurfacing using posterior and Ganz
      approaches at two years.
AB  - We report a retrospective review of femoral head/neck ratios on post-operative
      and two year follow-up radiographs following hip resurfacing arthroplasty. The
      patients were in two matched groups, having had surgery through a posterior
      approach or via a Ganz trochanteric flip. There was no significant difference in
      femoral neck narrowing at follow up between the two surgical approaches. However,
      we found significant narrowing of the femoral neck in both groups by the time of
      the two year follow-up radiograph.

PMID- 21948030
TI  - Outcome of short proximal femoral nail antirotation and dynamic hip screw for
      fixation of unstable trochanteric fractures. A randomised prospective comparative
      trial.
AB  - A prospective, randomised, controlled trial was performed to compare the outcome
      of treatment of unstable trochanteric fractures with either a short proximal
      femoral nail antirotation (PFNA) or dynamic hip screw (DHS). Eighty one patients
      with unstable fracture of the proximal part of the femur were randomised, at the
      time of admission, for fixation with either a short PFNA (n=42) or DHS (n= 39).
      The primary outcome measure was reoperation within the first postoperative year
      and mortality at the end of one year. Operative time, fluoroscopy time, blood
      loss, and any intra-operative complication were recorded for each patient.
      Clinical and radiological follow-up was undertaken for a minimum of 36 months.
      Any changes in the position of the implant or fixation failure were recorded. Hip
      range of motion, pain in the hip or thigh and return to work were used to compare
      the outcomes. There was no significant difference between 1 year mortality rates
      for the two groups. The mean operative time was significantly less in PFNA group
      (25 min) than in the DHS group (38 min). Patients treated with a PFNA experienced
      a shorter fluoroscopy time and less blood loss. Six patients in DHS group had
      implant failure while none experienced this in PFNA group. The PFNA group had a
      better functional outcome than the DHS group.

PMID- 21948031
TI  - Osteochondral mosaicplasty of the femoral head.
AB  - Young adults with osteochondral lesions of the femoral head are at risk of rapid
      progression to symptomatic arthritis of the hip joint. Between January 2008 and
      July 2009, 10 patients were treated for femoral cartilage damage by a
      osteochondral mosaicplasty of the femoral head through a trochanteric flap with
      dislocation of the hip. The consecutive series had the following exclusion
      criteria: acetabular chondropathy, age above 25 years, and femoral head
      osteonecrosis. Patients were followed up after surgery using the Oxford-12 score,
      Harris hip score and the Merle d'Aubigne score, and activity assessed by the UCLA
      and Devane scores. Radiological evaluation by computed tomographic (CT)
      arthrography was undertaken in all patients at 6 months and plain radiographs.
      Mean follow-up was 29.2 months (20-39 months). The Postel Merle d'Aubigne score
      improved from the pre-operative period to the latest follow-up, from 10.5 points
      (8-13) to 15.5 points (12-17). Global range of motion increased from 175.4
      degrees  (140-215) to 210.7 degrees  (175-240). All radiological investigations
      at latest follow-up showed that the autograft plugs were well-incorporated at the
      site of osteochondroplasty in the femoral head with intact cartilage over them
      and smooth interfaces between articulating bony surfaces. Osteochondral autograft
      transplantation may be a new alternative option for osteochondral lesions of the
      femoral head, but this has to be confirmed with longer follow-up and in a larger
      number of patients. The results of similar surgery in the knee have been mixed,
      and in the hip the technique is demanding, requiring familiarity with surgical
      hip dislocation.

PMID- 21948032
TI  - Total hip arthroplasties in young patients under 50 years: limited evidence for
      current trends. A descriptive literature review.
AB  - We examined all reported outcomes of uncemented and cemented total hip
      arthroplasty in patients younger than 50 years of age listed in Medline (1966- 1
      January 2009) and PubMed, and scrutinised reference lists of relevant papers. In
      addition, we evaluated relevant data in the Swedish hip arthroplasty register.
      109 relevant articles were identified, 37 of which had a mean follow-up longer
      than 10 years. Although uncemented implants are widely used in patients under 50
      years of age, there are only 2 reports that fulfil the criteria published by the
      National Institute for Clinical Excellence (NICE) in the United Kingdom (follow
      up of >10 yrs and survival of =90%). Current trends relating to implant selection
      remain unsupported by survival data, and additional information about the long
      term results of newer implants is essential. As matters stand, the most reliable
      results relate to cemented implants.

PMID- 21948033
TI  - Fracture of an Exeter 'cement in cement' revision stem: a case report.
AB  - The 'cement in cement' technique for revision hip arthroplasty has become popular
      in recent years, particularly in relation to polished taper stems. Since 2006 a
      short Exeter stem with 44 mm offset has been available specifically for this
      purpose. We report a fracture of such a stem in the absence of trauma 5 years
      after the revision procedure. The patient had a BMI of 27.8 and the proximal
      cement mantle gave good support to the stem. The fracture initiated and
      propagated from the introducer hole on the shoulder of the prosthesis.
      Macroscopically there was no defect in this area. This may be an unusual case of
      fatigue failure.

PMID- 21948035
TI  - Cemented versus uncemented hemiarthroplasty for hip fractures: a systematic
      review of randomised controlled trials.
AB  - We performed a systematic review of randomised controlled trials in order to
      identify the best available evidence to compare the outcome between cemented and
      uncemented hemiarthroplasty for treatment of intracapsular hip fractures. We
      searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register,
      the Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, MEDLINE and
      the National Research Register (UK) to retrieve all of the published randomised
      controlled trials designed to address these issues, in order to perform a meta
      analysis. Eight studies involving 1169 patients were determined to be appropriate
      for meta-analysis. The following statistically significant differences were found
      between the cemented and uncemented prostheses: (1) longer operative time for
      cemented prosthesis; (2) lower reduction in mobility score for those treated with
      cemented prosthesis; (3) fewer patients with residual pain in the hip and lower
      pain score (signifying less pain) for those treated with a cemented prosthesis.
      Our meta-analysis has shown that there is good evidence that the use of cement
      during hemiarthroplasty will reduce the amount of residual hip pain and also
      allow better restoration of function. There is no evidence of significant adverse
      effects of cement on mortality or other complications encountered. These
      observations apply to older designs, and there is a need for randomised trials
      comparing hydroxyapatite-coated modern stems with cemented prostheses.

PMID- 21948034
TI  - Metal ion interpretation in resurfacing versus conventional hip arthroplasty and
      in whole blood versus serum. How should we interpret metal ion data.
AB  - Metal ions generated from joint replacements are a cause for concern. There is no
      consensus on the best surrogate measure of metal ion exposure, and both serum and
      whole blood measurements are used in clinical practice. This study provides a
      guideline for interpretation of metal ion analysis in clinical practice. In a
      prospective trial comparing hip resurfacing (HR) with a conventional metal-on
      metal (MoM) total hip arthroplasty (THA) cobalt and chromium levels were
      determined for whole blood and serum in 343 paired samples at regular intervals
      up to 24 months postoperatively. Cobalt whole blood and serum levels increased
      significantly after both procedures. Cobalt concentrations were significantly
      higher for the HR group compared to the THA group, at 3, 6 and 12 months, for
      whole blood and serum. At 24 months cobalt levels decreased and differences
      between HR and THA were no longer significant. In contrast, chromium whole blood
      levels remained significantly higher for HR until 24 months. Whole blood and
      serum levels could not be used interchangeably. The mean differences for cobalt
      and chromium between blood and serum values were +0.13 ug/L and -0.91 ug/L
      respectively. Regression analysis provided a formula for conversion from serum to
      blood of 0.34+[0.88*Co serum] for cobalt and 0.14 + [0.58*Cr serum] for chromium,
      with an acceptable prediction error below +/-1.0 ug/L. Cobalt and chromium levels
      were significantly higher for HR versus THA, especially during the run-in phase
      of one year. Overall, the metal ion levels were well below 5 ug/L. We cannot
      recommend the use of whole blood over serum measurements or vice versa. The
      provided conversion formula between whole blood and serum in combination with the
      presented practical guidelines may be useful for clinical practice.

PMID- 21948036
TI  - Survival after pathological fractures of the proximal femur.
AB  - We report on the survival of 145 patients presenting to a single centre with a
      pathological metastatic fracture of the proximal femur. The single surviving
      patient had a follow-up of 17.7 years. Mean survival for the 144 patients who
      died was 332 days (range 2 to 3053 days), being longest for those with myeloma
      (662 days), lymphoma (> 633 days) and breast tumours (477 days) and lowest for
      lung tumours (110 days). The most common sites for the primary tumour were breast
      (36%), prostate (23%) and lung (17%). 47% of fractures were intracapsular, 28%
      trochanteric and 25% subtrochanteric. 99% of the fractures were treated
      surgically with a mean hospital stay of 19 days. The commonest fracture healing
      complication was further fracture of the femur around or immediately below the
      implant which occurred after 9/144 (6.2%) of operations. The difference in
      survival of patients related to the primary tumour site is of relevance in
      planning surgical treatment and discussing prognosis with patients.

PMID- 21948037
TI  - The NANOS short stem in total hip arthroplasty: a mid term follow-up.
AB  - A number of short stems for total hip arthroplasty have been introduced during
      the last decade. We describe our experience with the NANOS prosthesis (Smith and
      Nephew, Marl, Germany). The potential increase of bone mass around a femoral
      short stem using bone densitometry may be an indicator for secondary ingrowth. We
      report the outcome of 72 NANOS short stems in 65 patients between March 2003 and
      October 2007. The mean follow-up was 5.2+/-0.7 years and the mean age of the
      patients was 63+/-8.3 years. Along with demographic data and co-morbidities, the
      Harris Hip Score, the Merle d'Aubigne mobility score, and a patient-centred
      questionnaire were evaluated pre-operatively and during follow-up. The Mean
      Harris Hip Score increased from 47.3+/-12.2 pre-operatively to 97.6+/-0.6 at the
      final follow-up. The Merle d'Aubigne mobility score increased from 7.6+/-1.4 pre
      operatively to 11.8+/-0.3 at the final follow-up. None of the 72 stems were
      revised, providing a survival rate of 100%. Radiolucent lines were visible
      rasiographically in two patients during follow-up. The NANOS short stem
      demonstrated a satisfactory outcome at mid term follow-up. The clinical and
      radiological results support to the principle of metaphyseal anchorage of a short
      stem prosthesis. Long term evaluation will be of interest to determine if these
      encouraging trends are reflected by prolonged survivorship.

PMID- 21948038
TI  - Severe anaphylactic reaction to chlorhexidine during total hip arthroplasty
      surgery. A case report.
AB  - Two consecutive hip surgery procedures in the same patient were aborted following
      a severe anaphylactic reaction of the patient. After the second procedure, the
      patient was diagnosed to be allergic to chlorhexidine, a component of the gel
      used to insert a urinary catheter. Chlorhexidine allergy is rare, and the delayed
      presentation may make it easy to overlook. In hip arthroplasty surgery, this may
      result in an abandoned procedure and the need for re-operation.

PMID- 21948039
TI  - Dislocation rate after hip arthroplasty within the first postoperative year: 36
      mm versus 28 mm femoral heads.
AB  - Dislocation is a common and important complication of total hip arthroplasty
      (THA). Larger femoral heads may reduce the risk of dislocation and improve the
      range of movement. The aim of this study was to compare the relative risk (RR) of
      dislocation during the first year after THA between implants with 28 mm and 36 mm
      femoral heads. 198 consecutive hips with 28 mm femoral head (Group-28) and 259
      hips with 36 mm femoral head (Group-36) were studied. The patients were assessed
      preoperatively and periodically using the Harris hip score (HHS) and radiographic
      analysis. The relative risk (RR) of dislocation was calculated. The average HHS
      significantly improved from a preoperative baseline to the last follow-up at 82.1
      months (28 mm) and 44.3 months (36 mm). No statistically significant differences
      were revealed between the two groups for HHS results and complications (p>0.05),
      but the difference in RR of dislocation within the first year between the two
      groups was 7.85 (95% CI: 1.34-46.03), p=0.046.Although dislocation is
      multifactorial in etiology, the two groups were homogenous for all principal
      contributing factors except the diameter of the femoral head. Therefore, the use
      of 36-mm heads can reduce the risk of dislocation following THA by a factor of 8
      compared to conventional 28 mm heads.

PMID- 21948040
TI  - Reliability of the radiological assessments of radiolucency and loosening in
      total hip arthroplasty using PACS.
AB  - We evaluated the reliability of three commonly used radiological assessments of
      total hip arthroplasty (THA) using the electronic picture archiving and
      communications system (PACS). Thirty-three patients were selected at random at a
      mean of 7.2 years after THA. The Barrack, Gruen and Hodgkinson evaluations of
      cementing quality, loosening/radiolucency were graded. Three observers assessed
      each radiograph (one consultant orthopaedic surgeon, one senior orthopaedic
      registrar and one senior house officer). Four weeks after the initial assessment,
      each radiograph was reviewed a second time. The findings indicated that the intra
      and inter-observer reliability of the Barrack, Gruen and Hodgkinson methods were
      questionable. Inter-observer reliability using the Gruen system was poor, using
      the Barrack system it was moderate to good, and fair to good using the Hodgkinson
      assessment. Intra-observer reliability was moderate to good for Barrack
      assessment, poor to good using Gruen zone assessments, but good to very good for
      the Hodgkinson assessment. The use of Barrack, Gruen and Hodgkinson assessments
      to evaluate femoral and acetabular loosening should be questioned since these
      exhibit limited inter- and intra-observer reliability on PACS radiographs, but of
      the three, the Hodgkinson system is the most reliable.

PMID- 21948041
TI  - An information-motivation-behavioral skills (IMB) model-based intervention for
      CABG patients.
AB  - BACKGROUND: In order to benefit from a coronary artery bypass graft (CABG)
      surgery, patients must adhere to medical recommendations and health advices.
      Despite the importance of adherence in CABG patients, adherence rates are
      disappointingly low. Despite the low adherence rates, very few articles regarding
      adherence-enhancing intervention among heart patients have been published.
      PURPOSE: The goal of this study was to assess the effects of the Information
      Motivation-Behavioral Skills (IMB) model-based intervention on the IMB model
      constructs among patients undergoing CABG and to evaluate the relationship of
      information, motivation, and behavioral skills with adherence. METHOD: A total of
      152 CABG patients were randomly assigned to either an intervention group or to a
      standard care control group. Participants completed pretest measures and were
      reassessed 1 month later. RESULTS: Findings showed mixed support for the
      effectiveness of the intervention. There was a significant effect of IMB
      intervention on information and motivation of patients, but no significant effect
      on behavioral skills. Furthermore, the results revealed that intervention
      constructs (information, motivation, and behavioral skills) were significantly
      related to patients' adherence. CONCLUSIONS: Findings provided initial evidence
      for the effectiveness of IMB-based interventions on the IMB constructs and
      supported the importance of these constructs to improve adherence; however, there
      are additional factors that need to be identified in order to improve behavioral
      skills more effectively.

PMID- 21948042
TI  - Mandibular advancement devices are an alternative and valid treatment for
      pediatric obstructive sleep apnea syndrome.
AB  - BACKGROUND: Orthodontic and craniofacial abnormalities have often been reported
      in pediatric sleep-disordered breathing (SDB). While the reversibility of these
      craniofacial abnormalities by means of adenotonsillectomy has yet to be
      established, orthodontic treatment based on oral appliances is considered to be a
      potential additional treatment for pediatric SDB. DISCUSSION: Oral appliances may
      help improve upper airway patency during sleep by enlarging the upper airway
      and/or by decreasing upper airway collapsibility, thereby enhancing upper airway
      muscle tone. Orthodontic therapy should be encouraged in pediatric OSAS, and an
      early approach may permanently modify nasal breathing and respiration, thereby
      preventing obstruction of the upper airway.

PMID- 21948043
TI  - Etiology of obstructive sleep apnea--the number of nerve fibers at the base of
      the uvula seems important.

PMID- 21948044
TI  - The phosphotransferase VanU represses expression of four qrr genes antagonizing
      VanO-mediated quorum-sensing regulation in Vibrio anguillarum.
AB  - Vibrio anguillarum utilizes quorum sensing to regulate stress responses required
      for survival in the aquatic environment. Like other Vibrio species, V.
      anguillarum contains the gene qrr1, which encodes the ancestral quorum regulatory
      RNA Qrr1, and phosphorelay quorum-sensing systems that modulate the expression of
      small regulatory RNAs (sRNAs) that destabilize mRNA encoding the transcriptional
      regulator VanT. In this study, three additional Qrr sRNAs were identified. All
      four sRNAs were positively regulated by sigma(54) and the sigma(54)-dependent
      response regulator VanO, and showed a redundant activity. The Qrr sRNAs, together
      with the RNA chaperone Hfq, destabilized vanT mRNA and modulated expression of
      VanT-regulated genes. Unexpectedly, expression of all four qrr genes peaked at
      high cell density, and exogenously added N-acylhomoserine lactone molecules
      induced expression of the qrr genes at low cell density. The phosphotransferase
      VanU, which phosphorylates and activates VanO, repressed expression of the Qrr
      sRNAs and stabilized vanT mRNA. A model is presented proposing that VanU acts as
      a branch point, aiding cross-regulation between two independent phosphorelay
      systems that activate or repress expression of the Qrr sRNAs, giving flexibility
      and precision in modulating VanT expression and inducing a quorum-sensing
      response to stresses found in a constantly changing aquatic environment.

PMID- 21948045
TI  - DNA rearrangement has occurred in the carbazole-degradative plasmid pCAR1 and the
      chromosome of its unsuitable host, Pseudomonas fluorescens Pf0-1.
AB  - The carbazole-degradative plasmid pCAR1 carries the class II transposon Tn4676,
      which contains the car and ant genes, essential for conversion of carbazole into
      anthranilate, and anthranilate into catechol, respectively. In our previous
      study, DNA rearrangements in pCAR1 were frequently detected in the host
      Pseudomonas fluorescens Pf0-1 in the presence of carbazole, resulting in the
      improvement of host survivability. Several Pf0-1 mutants harbouring pCAR1 were
      isolated, and deletion of DNA in the plasmid ant gene was found. Here, we
      compared genome sequences of the parent strain Pf0-1L(pCAR1::rfp) and one of its
      mutants, 5EP83, to assess whether other DNA rearrangements occurred in either the
      plasmid or the host chromosome. We found transposition of Tn4676 into the 5EP83
      chromosome. In addition, ISPre1 had transposed into the car gene intergenic
      region on the pCAR1-derivative plasmid of 5EP83, which inhibited car
      transcription. As a result of these transpositions, 5EP83 was able to metabolize
      carbazole due to the Tn4676 on its chromosome, although the car genes on its
      plasmid were non-functional. We also found that one copy of duplicate carAa genes
      had been deleted, and that ISPre4 had transposed into both the host chromosome
      and the plasmid. Our findings suggest that Pf0-1 harbouring pCAR1 is subjected to
      DNA rearrangements not only on the plasmid but also on its chromosome in the
      presence of carbazole.

PMID- 21948046
TI  - Natural transformation with synthetic gene cassettes: new tools for integron
      research and biotechnology.
AB  - Integrons are genetic elements that can capture and express genes packaged as
      gene cassettes. Here we report new methods that allow integrons to be studied and
      manipulated in their native bacterial hosts. Synthetic gene cassettes encoding
      gentamicin resistance (aadB) and green fluorescence (gfp), or lactose metabolism
      (lacZY), were made by PCR and self-ligation, converted to large tandem arrays by
      multiple displacement amplification, and introduced into Escherichia coli or
      Pseudomonas stutzeri strains via electroporation or natural transformation.
      Recombinants (Gm(R) or Lac(+)) were obtained at frequencies ranging from 10(1) to
      10(6) c.f.u. (ug DNA)(-1). Cassettes were integrated by site-specific
      recombination at the integron attI site in nearly all cases examined (370/384),
      including both promoterless and promoter-containing cassettes. Fluorometric
      analysis of gfp-containing recombinants revealed that expression levels from the
      integron-associated promoter P(C) were five- to 10-fold higher in the plasmid
      borne integron In3 compared with the P. stutzeri chromosomal integrons.
      Integration of lacZY cassettes into P. stutzeri integrons allowed the bacteria to
      grow on lactose, and the lacZY gene cassette was stably maintained in the absence
      of selection. This study is believed to be the first to show natural
      transformation by gene cassettes, and integron-mediated capture of catabolic gene
      cassettes.

PMID- 21948047
TI  - The qid74 gene from Trichoderma harzianum has a role in root architecture and
      plant biofertilization.
AB  - The Trichoderma harzianum qid74 gene encodes a cysteine-rich cell wall protein
      that has an important role in adherence to hydrophobic surfaces and cellular
      protection; this gene was upregulated in Trichoderma high-density oligonucleotide
      (HDO) microarrays in interaction with tomato roots. Using a collection of qid74
      overexpressing and disrupted mutants the role of this gene in cucumber and tomato
      root architecture was analysed in hydroponic and soil systems under greenhouse
      conditions. No significant differences were found in the pattern of root
      colonization and the length of primary roots of cucumber or tomato plants
      inoculated by T. harzianum CECT 2413 wild-type (wt) strain or any of the qid74
      transformants. However, compared to the wt treatment, lateral roots were
      significantly longer in plants inoculated with the overexpressing transformants,
      and shorter in those treated with the disruptant strains. Microscopic
      observations revealed more and longer secondary root hairs in cucumber plants
      treated with the qid74-overexpressing mutants and fewer and shorter hairs in
      roots treated with qid74-disrupted transformants, compared to those observed in
      plants inoculated with the wt strain. qid74-induced modifications in root
      architecture increased the total absorptive surface, facilitating nutrient uptake
      and translocation of nutrients in the shoots, resulting in increased plant
      biomass through an efficient use of NPK and micronutrients.

PMID- 21948048
TI  - N-Acetylglucosamine-dependent biofilm formation in Pectobacterium atrosepticum is
      cryptic and activated by elevated c-di-GMP levels.
AB  - The phytopathogenic bacterium Pectobacterium atrosepticum (Pba) strain SCRI1043
      does not exhibit appreciable biofilm formation under standard laboratory
      conditions. Here we show that a biofilm-forming phenotype in this strain could be
      activated from a cryptic state by increasing intracellular levels of c-di-GMP,
      through overexpression of a constitutively active diguanylate cyclase (PleD*)
      from Caulobacter crescentus. Randomly obtained Pba transposon mutants defective
      in the pga operon, involved in synthesis and translocation of poly-beta-1,6-N
      acetyl-D-glucosamine (PGA), were all impaired in this biofilm formation. The
      presence of the PGA-degrading enzyme dispersin B in the growth media prevented
      biofilm formation by Pba overexpressing PleD*, further supporting the importance
      of PGA for biofilm formation by Pba. Importantly, a pga mutant exhibited a
      reduction in root binding to the host plant under conditions of high
      intracellular c-di-GMP levels. A modest but consistent increase in pga transcript
      levels was associated with high intracellular levels of c-di-GMP. Our results
      indicate tight control of PGA-dependent biofilm formation by c-di-GMP in Pba.

PMID- 21948049
TI  - Catabolite repression of phosphoenolpyruvate carboxykinase by a zinc finger
      protein under biotin- and pyruvate carboxylase-deficient conditions in Pichia
      pastoris.
AB  - We have identified a methanol- and biotin-starvation-inducible zinc finger
      protein named ROP [repressor of phosphoenolpyruvate carboxykinase (PEPCK)] in the
      methylotrophic yeast Pichia pastoris. When P. pastoris strain GS115 (wild-type,
      WT) is cultured in biotin-deficient, glucose-ammonium (Bio(-)) medium, growth is
      suppressed due to the inhibition of anaplerotic synthesis of oxaloacetate,
      catalysed by the biotin-dependent enzyme pyruvate carboxylase (PC). Deletion of
      ROP results in a strain (DeltaROP) that can grow under biotin-deficient
      conditions due to derepression of a biotin- and PC-independent pathway of
      anaplerotic synthesis of oxaloacetate. Northern analysis as well as microarray
      expression profiling of RNA isolated from WT and DeltaROP strains cultured in
      Bio(-) medium indicate that expression of the phosphoenolpyruvate carboxykinase
      gene (PEPCK) is induced in DeltaROP during biotin- or PC-deficiency even under
      glucose-abundant conditions. There is an excellent correlation between PEPCK
      expression and growth of DeltaROP in Bio(-) medium, suggesting that ROP-mediated
      regulation of PEPCK may have a crucial role in the biotin- and PC-independent
      growth of the DeltaROP strain. To our knowledge, ROP is the first example of a
      zinc finger transcription factor involved in the catabolite repression of PEPCK
      in yeast cells cultured under biotin- or PC-deficient and glucose-abundant
      conditions.

PMID- 21948050
TI  - Identification and classification of the genus Bacteroides by multilocus sequence
      analysis.
AB  - Multilocus sequence analysis (MLSA) was performed on representative species of
      the genus Bacteroides. Internal fragments of the genes selected, dnaJ, gyrB,
      hsp60, recA, rpoB and 16S rRNA, were amplified by direct PCR and then sequenced
      from 38 Bacteroides strains representing 35 species. Neighbour-joining (NJ),
      maximum-likelihood (ML) and maximum-parsimony (MP) phylogenies of the individual
      genes were compared. The data confirm that the potential for discrimination of
      Bacteroides species is greater using MLSA of housekeeping genes than 16S rRNA
      genes. Among the housekeeping genes analysed, gyrB was the most informative,
      followed by dnaJ. Analyses of concatenated sequences (4816 bp) of all six genes
      revealed robust phylogenetic relationships among different Bacteroides species
      when compared with the single-gene trees. The NJ, ML and MP trees were very
      similar, and almost fully resolved relationships of Bacteroides species were
      obtained, to our knowledge for the first time. In addition, analysis of a
      concatenation (2457 bp) of the dnaJ, gyrB and hsp60 genes produced essentially
      the same result. Ten distinct clades were recognized using the SplitsTree4
      program. For the genus Bacteroides, we can define species as a group of strains
      that share at least 97.5% gene sequence similarity based on the fragments of five
      protein-coding housekeeping genes and the 16S rRNA gene. This study demonstrates
      that MLSA of housekeeping genes is a valuable alternative technique for the
      identification and classification of species of the genus Bacteroides.

PMID- 21948051
TI  - Reconstruction plate versus minimal invasive retrograde titanium elastic nail
      fixation for displaced midclavicular fractures.
AB  - BACKGROUND: Nonoperative management of midshaft clavicle fractures (MSCFs) is
      standard; however, it is now generally accepted that displaced midshaft clavicle
      fractures benefit from internal fixation. Plating and intramedullary fixation
      have become the accepted methods of fixation. The purpose of this study was to
      see if one method of fixation of clavicle fractures has a lower complication rate
      and higher union rate than the other. MATERIALS AND METHODS: Between December
      2003 and September 2008, 38 patients were treated randomly by either plating
      (plate group) or retrograde nailing (RTEN group). Primary outcome measures
      included functional Constant scores, radiological union rate and union time.
      Clinical and radiological assessments were performed at the 6th week and the 3rd,
      6th and 12th month postoperatively. Secondary outcome measures included the
      perioperative data (mean surgery time, blood loss, wound size, and hospital
      stay), and the complication rates. RESULTS: Similar results were found between
      the two groups regarding functional and radiological outcome after the 12th week
      (P > 0.05). However, earlier union and functional recovery were obtained at the
      6th week for the RTEN group (P < 0.05). The rate of complications was
      significantly higher (15.8%) in the plate group compared with the RTEN group (0%;
      P > 0.05). In the plate group, significantly higher values were obtained for the
      perioperative data (P < 0.001). CONCLUSION: Both techniques are equally effective
      at treating displaced midclavicular fractures, and give better function and fewer
      complications than nonoperative treatment. The RTEN technique has more advantages
      and lower complications than plating, making its use more favorable. It is
      recommended for athletes and young active individuals, and can be used as an
      alternative to conservative treatment or plate fixation.

PMID- 21948052
TI  - Macrodystrophia lipomatosa involving multiple nerves.
AB  - Macrodystrophia lipomatosa (MDL), a rare congenital disorder, is considered by
      some to be a localized form of Proteus syndrome. The implication of the PTEN
      (phosphatase and tensin homolog deleted on chromosome 10) gene in both
      strengthens this belief. We present a case who had MDL in multiple nerve
      territories--all on the same side of the body--with hypertrophy of mainly
      fibroadipose tissue throughout their distribution, thus pointing to a form of
      localized hemihypertrophy; both hemihypertrophy and lipomatous tumors are
      components of Proteus syndrome.

PMID- 21948053
TI  - Growing discontent of Swiss doctors, 1998-2007.
AB  - BACKGROUND: Work satisfaction of doctors is a useful indicator of the functioning
      of the health-care system. We documented the work satisfaction of doctors nine
      years apart, before and after the implementation of several health-care reforms
      (limitation of working hours for medical trainees, restrictions on new doctors'
      offices, new reimbursement fee schedule, greater administrative controls).
      METHODS: Two surveys of all doctors working in the Canton of Geneva, Switzerland
      (1998: 1146 respondents, 2007: 1546 respondents). The doctors filled in a 17-item
      questionnaire rating their satisfaction with different aspects of their
      professional life, each on a scale between 1 and 7. For each item, proportions of
      highly satisfied (scores 6-7) and highly dissatisfied (scores 1-2) doctors were
      compared over time. RESULTS: The proportion of doctors who were highly satisfied
      decreased significantly for 15 out of 17 items between 1998 and 2007. Meanwhile,
      'time available for family, friends, or leisure' improved, and 'opportunity for
      continuing education' remained stable. Proportions of highly satisfied
      respondents decreased the most for 'enjoyment of work' (-17.2%), 'autonomy in
      treating your patients' (-15.8%), 'autonomy in referring patients to a
      specialist' (-14.0%), 'relations with patients' (-13.9%) and 'global satisfaction
      with current work situation' (-13.3%). The proportion of respondents who were
      highly dissatisfied (score 1-2) increased the most for 'administrative burden'
      (+8.9%) and 'social status and respect' (+5.0%). CONCLUSIONS: Doctors'
      satisfaction with most aspects of their professional lives has decreased sharply
      during the past decade. This trend may be linked, tentatively, with specific
      policy changes.

PMID- 21948054
TI  - Uveitis as the initial manifestation of diffuse large B-cell lymphoma.

PMID- 21948055
TI  - High diastolic blood pressure is a risk factor for in-hospital mortality in
      complete MCA stroke patients.
AB  - Complete middle cerebral artery (MCA) stroke is a life-threatening condition,
      which can lead to death in the form of "malignant MCA syndrome"; characterized by
      massive brain edema and cerebral herniation. Moreover, patients with complete MCA
      infarct have high mortality due to complications. The aim of this study was to
      evaluate the clinical predictors of in-hospital mortality in patients with
      complete MCA stroke. Consecutive patients with complete MCA stroke were enrolled
      in a prospective single center in-hospital outcome study having mortality as its
      end point. Among 780 ischemic stroke patients, 125 had complete MCA strokes (16%)
      and 44 (35.2%) of these died in hospital. A high NIHSS-score (OR 1.17 95%CI 1.03
      1.34, P=0.013) and high diastolic blood pressure on admission (OR 1.05 95%CI 1.01
      1.09) resulted being independent predictors of in-hospital mortality in patients
      with complete MCA stroke. The median value of diastolic blood pressure at
      admission was 90 mmHg in patients who died and 80 mmHg in survivors (P=0.01). The
      risk of death increased by 5% for each mmHg increase in diastolic blood pressure
      on admission after adjusting for other risk factors. The rate of mortality was
      22% in patients with diastolic blood pressure lower than 90 mmHg, 56% for those
      with diastolic blood pressure between 90 and 109 mmHg and 67% for those with
      diastolic blood pressure higher than 110 mmHg. This study suggests that high
      diastolic blood pressure on admission in acute MCA stroke patients is linearly
      correlated with in-hospital mortality.

PMID- 21948056
TI  - Myotonic dystrophy type 2 and autoimmune chronic gastritis: an incidental
      association?

PMID- 21948057
TI  - Recommendations for the management of urinary disorders in multiple sclerosis: a
      consensus of the Italian Multiple Sclerosis Study Group.
AB  - Urinary disorders are uncommon in the initial phases of multiple sclerosis, but
      increase in frequency as the disease progresses, with a negative impact on
      quality of life. The goal of this study was to propose a protocol for the
      diagnosis and treatment of urinary disorders in multiple sclerosis, based on data
      from the scientific literature and the experience of Italian clinical centres. In
      particular, the following clinical aspects were considered: what to do with
      patients with asymptomatic multiple sclerosis; what to do with symptomatic
      patients; how and when to perform a second-level diagnostic evaluation; and how
      to treat urinary disorders. A diagnostic-therapeutic algorithm is proposed, that
      can be applied in Italian clinical centres.

PMID- 21948058
TI  - Chorea mollis: long-term follow-up of an infantile case.
AB  - We describe the long-term follow-up of a patient affected by chorea mollis, a
      rare variant of Sydenham's chorea of which there are very few reports in the
      literature. Our patient, a previously healthy 8-year-old boy developed
      progressive clumsiness, gait disturbance, generalised hypotonia and muscle
      weakness, choreic movements of the limbs and behavioural disturbances. Following
      the diagnosis of chorea mollis, the patient received prophylaxis (monthly
      injections of benzathine benzyl penicillin). Within a few weeks, his clinical
      conditions worsened and he became bedridden and incapable of standing and walking
      without assistance. The choreic movements were successfully treated with sodium
      valproate. Independent walking was achieved 14 months after the onset of the
      disease. At a 4-year follow-up, the patient showed a full neurological and
      psychiatric recovery. The clinical course observed in our patient shows that
      chorea mollis may not only have a dramatic course, but also have a good long-term
      prognosis.

PMID- 21948059
TI  - Beyond the intention-to-treat in comparative effectiveness research.
AB  - BACKGROUND: The intention-to-treat comparison is the primary, if not the only,
      analytic approach of many randomized clinical trials. PURPOSE: To review the
      shortcomings of intention-to-treat analyses, and of 'as treated' and 'per
      protocol' analyses as commonly implemented, with an emphasis on problems that are
      especially relevant for comparative effectiveness research. METHODS AND RESULTS:
      In placebo-controlled randomized clinical trials, intention-to-treat analyses
      underestimate the treatment effect and are therefore nonconservative for both
      safety trials and noninferiority trials. In randomized clinical trials with an
      active comparator, intention-to-treat estimates can overestimate a treatment's
      effect in the presence of differential adherence. In either case, there is no
      guarantee that an intention-to-treat analysis estimates the clinical
      effectiveness of treatment. Inverse probability weighting, g-estimation, and
      instrumental variable estimation can reduce the bias introduced by nonadherence
      and loss to follow-up in 'as treated' and 'per protocol' analyses. LIMITATIONS:
      These analyse require untestable assumptions, a dose-response model, and time
      varying data on confounders and adherence. CONCLUSIONS: We recommend that all
      randomized clinical trials with substantial lack of adherence or loss to follow
      up are analyzed using different methods. These include an intention-to-treat
      analysis to estimate the effect of assigned treatment and 'as treated' and 'per
      protocol' analyses to estimate the effect of treatment after appropriate
      adjustment via inverse probability weighting or g-estimation.

PMID- 21948061
TI  - Characterization of Prototheca wickerhamii isolated from disseminated algaemia of
      kidney transplant patient from Malaysia.
AB  - Prototheca wickerhamii isolated from blood of 61-year-old kidney transplant
      patient was described. Although it is classified as an alga (genus Chlorella),
      the disease, protothecosis, is included under mycoses because of its clinical
      pathological presentations. Colony characteristics of P. wickerhamii are
      indistinguishable from other yeast-like organisms like Cryptococcus and Candida.
      Fortunately, commercial identification system for yeast can be used to identify
      this organism to the species level. Electron microscopy demonstrated "morula" or
      daisy-like appearance of its endosporulating sporangia. The organism was
      sensitive to amphotericin B by E test method. Even though human protothecosis is
      uncommon, it cannot be ignored because it is emerging as an opportunistic
      infection in immunosuppressed individuals. To our knowledge, this is the first
      reported case of disseminated algaemia due to P. wickerhamii in Malaysia.

PMID- 21948060
TI  - Genetic approaches to investigate the role of CREB in neuronal plasticity and
      memory.
AB  - In neurons, the convergence of multiple intracellular signaling cascades leading
      to cAMP-responsive element-binding protein (CREB) activation suggests that this
      transcription factor plays a critical role in integrating different inputs and
      mediating appropriate neuronal responses. The nature of this transcriptional
      response depends on both the type and strength of the stimulus and the cellular
      context. CREB-dependent gene expression has been involved in many different
      aspects of nervous system function, from embryonic development to neuronal
      survival, and synaptic, structural, and intrinsic plasticity. Here, we first
      review the different methodological approaches used to genetically manipulate
      CREB activity and levels in neurons in vivo in the adult brain, including
      recombinant viral vectors, mouse transgenesis, and gene-targeting techniques. We
      then discuss the impact of these approaches on our understanding of CREB's roles
      in neuronal plasticity and memory in rodents. Studies combining these genetic
      approaches with electrophysiology and behavior provide strong evidence that CREB
      is critically involved in the regulation of synaptic plasticity, intrinsic
      excitability, and long-term memory formation. These findings pave the way for the
      development of novel therapeutic strategies to treat memory disorders.

PMID- 21948063
TI  - An improved non-enzymatic "DNA ladder assay" for more sensitive and early
      detection of apoptosis.
AB  - Conventional DNA ladder assay has certain shortcomings such as loss of DNA
      fragments during sample processing, involvement of multiple steps and requirement
      of expensive reagents. The present study demonstrates a rapid, easy-to-perform
      cost-effective method for detection of apoptotic DNA fragments with considerable
      improvement in the sensitivity by avoiding loss of DNA fragments. It involves a
      few minutes of procedure involving direct lysis of cells with dimethyl sulphoxide
      (DMSO), brief vortexing, addition of 2% SDS-TE buffer, and a single step of
      centrifugation. This cost- and time-efficient method reduces the assay time
      considerably and can be used for a large number of samples with excellent
      sensitivity.

PMID- 21948064
TI  - Why We Do Things Differently: Leaders and Followers?

PMID- 21948062
TI  - Ten challenges on Cryptococcus and cryptococcosis.
AB  - Cryptococcosis has become a significant public global health problem worldwide.
      Caused by two species, Cryptococcus neoformans or Cryptococcus gattii, this life
      threatening infection afflicts not only immunocompromised individuals but also
      apparently immunocompetent subjects. Hence, cryptococcosis should no longer be
      considered merely an opportunistic infection. In this article, we focus on ten
      unanswered questions/topics in this field with the hope to stimulate discussion
      and research on these topics that would lead not only to a better understanding
      of the physiopathology of this disease but also to a better diagnosis and
      prognosis.

PMID- 21948066
TI  - Perioperative metabolic alkalemia is more frequent than metabolic acidemia in
      major elective abdominal surgery.
AB  - OBJECTIVE: To investigate the incidence, type and etiology of perioperative
      metabolic disturbances associated with major abdominal surgery. We hypothesized
      that metabolic alkalemia is more frequent than metabolic acidemia. METHODS: This
      was a prospective, observational study, performed in a university-affiliated
      hospital. 98 consecutive patients undergoing major abdominal surgery were
      included in the study. Patients were observed by serial vital signs and
      laboratory measurements during the preoperative, intraoperative, PACU and the
      first three postoperative day periods. Central venous pressure, systolic pressure
      variation, fluid input, urine output, temper- ature, electrolytes, and acid-base
      variables were recorded. The primary endpoint of the study was the incidence of
      metabolic alkalemia or acidemia. Metabolic alkalemia was defined as pH >7.45 and
      BE >+3. Metabolic acidemia was defined as pH <7.35 and BE <-3. Continuous
      variables were described as mean +/- standard deviation. Distributions of
      continuous variables was assessed for normalty using the Kolmogorov-Smirnov test 
      (cut off at P = 0.01). The frequency of metabolic acidemia or alkalemia was
      compared across time points using Cochran's  Q test and between time points using
      the binomial distribution. RESULTS: Metabolic acidemia occurred only
      intraoperatively and in the PACU. Subjects with metabolic acidemia were older,
      (74 +/- 9 yr. vs. 66 +/- 12, P = 0.01). Intraoperative body temperature was
      inversely associated with PACU lactate (P = 0.035). Blood loss >500 mL was more
      frequent in acidemic patients (42% vs. 19%, P = 0.033). More patients with
      hyperphosphatemia had acidemia than subjects without hyperphosphatemia (39% vs.
      17%, P = 0.019). Metabolic alkalemia occurred more frequently than metabolic
      acidemia (49% vs. 23%, P < 0.0001) and was correlated  with hypochloremia. The
      incidence of metabolic alkalemia decreased from baseline to intraoperative and
      PACU periods (13% vs. 3%, P = 0.003) and increased from the PACU to  the three
      postoperative days (3% vs. 45%, P = 0.007). CONCLUSIONS: Metabolic alkalemia
      occurred more frequently than metabolic acidemia and occurred mainly
      preoperatively and  postoperatively, while acidemia occurred mainly during
      surgery and in the PACU.

PMID- 21948067
TI  - The impact of induction of general anesthesia and a vascular occlusion test on
      tissue oxygen saturation derived parameters in high-risk surgical patients.
AB  - OBJECTIVES: Tissue oxygen saturation (StO(2)) assessed using Near Infrared
      Spectroscopy and its derived parameters during a vascular occlusion test (VOT)
      can detect microvascular changes in septic shock patients. General anesthesia
      (GA) impacts microcirculation. Our aim was to study the effects of general
      anesthesia on StO(2) and StO(2) derived parameters obtained during VOT in
      patients referred for cardiac surgery. METHODS: We studied 15 patients referred
      for cardiac surgery before and after induction of GA. Before GA induction, we
      also studied 15 healthy volunteers (non patients) in order to compare baseline
      physiological data between patients and healthy subjects. Hemodynamic and
      microcirculatory (StO(2), ischemic slope, reperfusion slope, and hyperemic
      response) data were recorded at each step. We used the Inspectra StO(2) system
      (Hutchinson Inc, MN, USA) with a sensor placed on the thenar eminence. StO(2)
      values were obtained at baseline and during  a VOT. A sphyngomanometer was placed
      on the forearm  above the StO(2) probe and the cuff was then rapidly inflated 30
      mmHg above systolic pressure and was maintained inflated  until the StO(2) value
      reached 40%. It was then rapidly deflated. RESULTS: Healthy volunteers had
      significantly higher reperfusion slope than patients (348 [251-393] vs. 261 [185
      279] %/min; P < 0.05). GA induction induced no significant change in StO(2) value
      compared to baseline (79 [75-85] vs. 80 [76-86]%; P = 0.57). We observed a
      significant decrease in ischemic slope (from -12 [-16--8] to -8 [-10--6] %/min; P
      = 0.004) and in reperfusion slope (from 261 [185-279] %/min to 164 [151-222]
      %/min; P = 0.008) suggesting a decrease in local metabolic rate and a negative
      impact on reperfusion reserve induced by anesthesia. CONCLUSION: StO(2) derived
      parameters during a VOT are impacted by GA induction. These parameters may have
      potential for microcirculation assessment in patients undergoing surgery.

PMID- 21948068
TI  - Decrease in pulmonary artery pressure after administration of thoracic epidural
      anesthesia in a patient with Marfan syndrome awaiting aortic valve replacement
      procedure.
AB  - Thoracic epidural anesthesia is an adjunct to general anesthesia in cardiac
      surgery. Decrease in heart rate and blood pressure are frequently seen beneficial
      effects. There are several other hemodynamic effects of thoracic epidural
      anesthesia such as decrease in systemic vascular resistance, cardiac index, left
      ventricular stroke work index among others. However, the effect of thoracic
      epidural anesthesia on pulmonary artery pressure (PAP) has not been studied
      extensively in humans. Thoracic epidural anes-thesia decreased pulmonary artery
      pressure in experimen-tally induced pulmonary hypertension in animals. The
      mechanisms involved in such reduction are ill understood. We describe in this
      report, a significant reduction in PAP in a patient with Marfan's syndrome
      scheduled to under-go aortic valve replacement. The possible mechanisms of
      decrease in pulmonary artery pressure in the described case are, decrease in the
      venous return to the heart, decrease in the systemic vascular resistance,
      decrease in the right ventric-ular function and finally, improvement in
      myocardial contraction secondary to all the above. The possibility of Marfan's
      syndrome contributing to the decrease in PAP appears remote. The authors present
      this case to generate discussion about the possible mechanisms involved in
      thoracic epidural anesthesia producing beneficial effects in patients with
      secondary pulmonary hypertension. Thoracic epidural anesthesia appears to
      decrease pulmonary artery pressure by a combination of several mechanisms, some
      unknown to us. This occurrence, if studied and understood well could be put to
      clinical use in pulmonary hypertensives.

PMID- 21948069
TI  - Pharmacodynamic modeling of propofol-induced tidal volume depression in children.
AB  - OBJECTIVE: This investigation aimed to develop a pediatric pharmacodynamic model
      of propofol-induced tidal volume depression towards an ultimate goal of
      developing a dosing schedule that would preserve spontaneous breathing following
      a loading dose of propofol. METHODS: Fifty two ASA 1 and 2 children aged 6-15
      year presenting for gastrointestinal endoscopy were enrolled. Subjects were
      administered a loading dose of 4 mg/kg of propofol intravenously at a constant
      infusion rate determined by a randomization schedule. Respiratory parameters
      including tidal volume, respiratory rate, minute volume, and end-tidal CO(2) were
      recorded at 5 s intervals. Using the predicted plasma concentration, based on the
      Paedfusor pharmacokinetic model, propofol-induced tidal volume depression was
      modeled by 3 different approaches  (2-stage, pooled, and mixed effects) and
      results were compared using prediction residual, median percentage errors, median
      absolute percentage errors, and root-mean-squared normalized errors. The effects
      of age and body weight as covariates were examined. RESULTS: Respiratory rate and
      end-tidal CO(2) did not show clear dependence on the predicted plasma
      concentration. The pharmacodynamic models for tidal volume derived  from
      different modeling approaches were highly consistent. The 2-stage, pooled, and
      mixed effects approaches yielded  k(e0) of 1.06, 1.24, and 0.72 min(-1); gamma of
      1.10, 0.83, and 0.93; EC50 of 3.18, 3.44, and 3.00 mcg/ml. Including age and 
      body weight as covariates did not significantly improve the predictive
      performance of the models. CONCLUSIONS: A pediatric pharmacodynamic model of
      propofol-induced tidal volume depression was developed. Models derived from 3
      different approaches were shown to be consistent with each other; however, the
      individual pharmacodynamic parameters exhibited significant inter-individual
      variability without strong dependence on age and body weight. This would suggest
      the desirability of adapting the pharmacodynamic model to each subject in real
      time.

PMID- 21948070
TI  - New insights on the origin of B chromosomes in Astyanax scabripinnis obtained by
      chromosome painting and FISH.
AB  - Chromosome painting (CP) with a probe of B chromosome obtained by microdissection
      and fluorescence in situ hybridization (FISH) with probes of As51 satellite DNA,
      C( o )t-1 DNA, and 18S and 5S rDNA confirmed sharing of some repetitive DNA but
      not rDNA between A and B chromosomes in the fish Astyanax scabripinnis. Meiotic
      analysis revealed a pachytene B chromosome bivalent nearly half the size of its
      mitotic configuration, suggesting a self-pairing of B chromosome arms. Such an
      isochromosome nature of somatic B chromosome was further evidenced by CP and
      FISH. All the findings obtained suggest (i) intraspecific origin of B chromosome,
      and (ii) evolutionary enrichment of repetitive DNA classes, especially those
      contained in the C( o )t-1 and the As51 probes, in B chromosome. However, the
      precise origin of B chromosome in the present species remains to be elucidated by
      further molecular cytogenetic analysis because of painting of some A chromosome
      regions with the B chromosome-derived probe.

PMID- 21948071
TI  - Orthopedic gene therapy--lost in translation?
AB  - Orthopedic gene therapy has been the topic of considerable research for two
      decades. The preclinical data are impressive and many orthopedic conditions are
      well suited to genetic therapies. But there have been few clinical trials and no
      FDA-approved product exists. This paper examines why this is so. The reasons are
      multifactorial. Clinical translation is expensive and difficult to fund by
      traditional academic routes. Because gene therapy is viewed as unsafe and risky,
      it does not attract major funding from the pharmaceutical industry. Start-up
      companies are burdened by the complex intellectual property environment and
      difficulties in dealing with the technology transfer offices of major
      universities. Successful translation requires close interactions between
      scientists, clinicians and experts in regulatory and compliance issues. It is
      difficult to create such a favorable translational environment. Other promising
      fields of biological therapy have contemplated similar frustrations approximately
      20 years after their founding, so there seem to be more general constraints on
      translation that are difficult to define. Gene therapy has noted some major
      clinical successes in recent years, and a sense of optimism is returning to the
      field. We hope that orthopedic applications will benefit collaterally from this
      upswing and move expeditiously into advanced clinical trials.

PMID- 21948072
TI  - Sleep findings and predictors of sleep desaturation in adult cystic fibrosis
      patients.
AB  - PURPOSE: Questions remain about the polysomnographic findings and the predictors
      for sleep desaturation in cystic fibrosis (CF) patients. Our study aimed to
      evaluate sleep parameters in a sample of adult CF patients comparing them with
      healthy controls and to determine the best predictors of sleep desaturation in CF
      patients with awake resting peripheral oxygen saturation (SpO(2)) >=90%. METHODS:
      In a cross-sectional study, with data collected prospectively, 51 clinically
      stable adult CF patients (mean age 25.1 +/- 6.7 years) and 25 age-matched
      controls underwent an overnight polysomnography and answered sleep
      questionnaires. CF patients had their pulmonary function, 6-min walk test, and
      echocardiography assessed. RESULTS: CF patients and control subjects had similar
      sleep architecture. However, CF patients had impaired subjective sleep quality
      and a higher arousal index than controls. The apnea-hypopnea index was similar in
      both groups, and only two CF patients (3.9%) fulfilled the criteria for
      obstructive sleep apnea syndrome. Sleep desaturation was more common in CF
      patients (29.4% vs 0%; p < 0.001). In a logistic regression model, we observed
      that awake resting SpO(2) was the single best variable associated with sleep
      desaturation in CF population (p < 0.001). The awake SpO(2) <94% had a
      sensitivity, specificity, positive and negative predictive value for sleep
      desaturation of, respectively, 93.3%, 100%, 100%, and 97.3%. CONCLUSIONS: CF
      patients had a worse subjective sleep quality and small changes in sleep
      architecture. In nonhypoxic, adult CF patients, sleep desaturation is common, is
      not associated with obstructive sleep events, and can be accurately predicted by
      awake resting SpO(2) <94%.

PMID- 21948073
TI  - Clinical and imaging characteristics of cerebral schistosomiasis.
AB  - In recent years, there has been a trend for increased incidence of cerebral
      schistosomiasis. It is often misdiagnosed because of the diversity of clinical
      symptoms. We wished to explore clinical characteristics and imaging findings in
      cerebral schistosomiasis. We retrospectively analyzed clinical data, laboratory
      tests, CT, and MRI results in 11 patients with cerebral schistosomiasis. All
      patients had chronic cerebral schistosomiasis (five with epilepsy type, five with
      brain tumor type, and one patient with stroke type). All patients with brain
      tumor type were misdiagnosed as having gliomas. There were typical findings on CT
      and MRI. In conclusion, clinical manifestations of cerebral schistosomiasis are
      variable, and the rate of misdiagnosis is high. For more precise diagnosis, a
      combination of laboratory and imaging data is required.

PMID- 21948074
TI  - Cardioprotective effects of an aminothiazole compound on isoproterenol-induced
      myocardial injury in mice.
AB  - Dendrodoine analogue (DA), an aminothiazole compound derived from dendrodoine,
      present in a marine tunicate, has been shown to possess many beneficial
      properties. This study was aimed to evaluate its cardioprotective effect against
      isoproterenol (ISO)-induced myocardial damage in mice. Swiss mice were pretreated
      with DA for 7 days and then treated with ISO (5 mg/kg BW, for 2 consecutive
      days). Biochemical assessment of myocardial injury was carried out by measuring
      marker enzymes, antioxidant enzymes and levels of lipid peroxidation.
      Histological studies of hearts were also carried out. ISO administration
      increased the activities of creatine kinase-MB, lactate dehydrogenase and
      aspartate aminotranferase (AST) in serum. Prior administration of DA restored the
      levels of these enzymes and the heart coefficient close to normal levels. DA at a
      concentration of 5 mg/kg BW was most effective in reducing AST, and this
      concentration was used for further studies. DA also gave significant protection
      against lipid peroxidation in the heart besides restoring histopathological
      alterations. DA showed significant reactivity towards superoxide radicals. In
      conclusion our study indicates that DA can protect mouse myocardium against
      damage and one of the possible reasons behind this protective effect can be
      attributed to its antioxidant property. 

PMID- 21948076
TI  - Accessory extensor digiti secundus muscle: some interesting facts.

PMID- 21948075
TI  - Comprehensive visualization of multimodal cardiac imaging data for assessment of
      coronary artery disease: first clinical results of the SMARTVis tool.
AB  - PURPOSE: In clinical practice, both coronary anatomy and myocardial perfusion
      information are needed to assess coronary artery disease (CAD). The extent and
      severity of coronary stenoses can be determined using computed tomography
      coronary angiography (CTCA); the presence and amount of ischemia can be
      identified using myocardial perfusion imaging, such as perfusion magnetic
      resonance imaging (PMR). To determine which specific stenosis is associated with
      which ischemic region, experts use assumptions on coronary perfusion territories.
      Due to the high variability between patient's coronary artery anatomies, as well
      as the uncertain relation between perfusion territories and supplying coronary
      arteries, patient-specific systems are needed. MATERIAL AND METHODS: We present a
      patient-specific visualization system, called Synchronized Multimodal heART
      Visualization (SMARTVis), for relating coronary stenoses and perfusion deficits
      derived from CTCA and PMR, respectively. The system consists of the following
      comprehensive components: (1) two or three-dimensional fusion of anatomical and
      functional information, (2) automatic detection and ranking of coronary stenoses,
      (3) estimation of patient-specific coronary perfusion territories. RESULTS: The
      potential benefits of the SMARTVis tool in assessing CAD were investigated
      through a case-study evaluation (conventional vs. SMARTVis tool): two experts
      analyzed four cases of patients with suspected multivessel coronary artery
      disease. When using the SMARTVis tool, a more reliable estimation of the relation
      between perfusion deficits and stenoses led to a more accurate diagnosis, as well
      as a better interobserver diagnosis agreement. CONCLUSION: The SMARTVis
      comprehensive visualization system can be effectively used to assess disease
      status in multivessel CAD patients, offering valuable new options for the
      diagnosis and management of these patients.

PMID- 21948077
TI  - Fashions in genital fashion: where is the line for physicians? Commentary on
      Veale and Daniels (2011).

PMID- 21948078
TI  - Constructing masculinity in response to women's sexual advances.
AB  - Drawing on 20 in-depth interviews with men who reported unwanted sexual
      experiences with women as adults, this article addresses how masculinity informs
      their lived experiences of this type of contact. One of the main themes that
      emerged from this research was that participants constructed masculinity by
      engaging in sexual gatekeeping or setting limits on women's sexual advances.
      Whereas sexual gatekeeping has been perceived as a passive role for women, it may
      be entirely agentic for men. That is, sexual gatekeeping played a vital role in
      preserving the gender dichotomy that informed the traditional sexual script for
      our participants. Since it is consistent with masculinity to take a proactive
      role in heterosexual sex, a man's perceived sexual objectification by an
      initiative woman can be experienced as a violation. In order to regain their
      proactive role, male participants set limitations on women's sexual advances.

PMID- 21948079
TI  - Perception of facial expression depends on prior attention.
AB  - Attending versus ignoring a stimulus can later determine how it will be
      affectively evaluated. Here, we asked whether attentional states could also
      modulate subsequent sensitivity to facial expressions of emotion. In a dual-task
      procedure, participants first rapidly searched for a gender-defined face among
      two briefly displayed neutral faces. Then a test face with the previously
      attended or ignored face's identity was presented, and participants judged
      whether it was emotionally expressive (happy, angry, or fearful) or neutral.
      Intensity of expression in the test face was varied so that an expression
      detection threshold could be determined. When fearful or angry expressions were
      judged, expression sensitivity was worse for faces bearing the same identity as a
      previously ignored versus attended face. When happy expressions were judged,
      sensitivity was unaffected by prior attention. These data support the notion that
      the motivational value of stimuli may be reduced by processes associated with
      selective ignoring.

PMID- 21948080
TI  - The p.Arg63Trp polymorphism controls Vav1 functions and Foxp3 regulatory T cell
      development.
AB  - CD4(+) regulatory T cells (T(reg) cells) expressing the transcription factor
      Foxp3 play a pivotal role in maintaining peripheral tolerance by inhibiting the
      expansion and function of pathogenic conventional T cells (T(conv) cells). In
      this study, we show that a locus on rat chromosome 9 controls the size of the
      natural T(reg) cell compartment. Fine mapping of this locus with interval
      specific congenic lines and association experiments using single nucleotide
      polymorphisms (SNPs) identified a nonsynonymous SNP in the Vav1 gene that leads
      to the substitution of an arginine by a tryptophan (p.Arg63Trp). This p.Arg63Trp
      polymorphism is associated with increased proportion and absolute numbers of
      T(reg) cells in the thymus and peripheral lymphoid organs, without impacting the
      size of the T(conv) cell compartment. This polymorphism is also responsible for
      Vav1 constitutive activation, revealed by its tyrosine 174 hyperphosphorylation
      and increased guanine nucleotide exchange factor activity. Moreover, it induces a
      marked reduction in Vav1 cellular contents and a reduction of Ca(2+) flux after
      TCR engagement. Together, our data reveal a key role for Vav1-dependent T cell
      antigen receptor signaling in natural T(reg) cell development.

PMID- 21948081
TI  - Tolerogenic function of Blimp-1 in dendritic cells.
AB  - Blimp-1 has been identified as a key regulator of plasma cell differentiation in
      B cells and effector/memory function in T cells. We demonstrate that Blimp-1 in
      dendritic cells (DCs) is required to maintain immune tolerance in female but not
      male mice. Female mice lacking Blimp-1 expression in DCs (DCBlimp-1(ko)) or
      haploid for Blimp-1 expression exhibit normal DC development but an altered DC
      function and develop lupus-like autoantibodies. Although DCs have been implicated
      in the pathogenesis of lupus, a defect in DC function has not previously been
      shown to initiate the disease process. Blimp-1(ko) DCs display increased
      production of IL-6 and preferentially induce differentiation of follicular T
      helper cells (T(FH) cells) in vitro. In vivo, the expansion of T(FH) cells is
      associated with an enhanced germinal center (GC) response and the development of
      autoreactivity. These studies demonstrate a critical role for Blimp-1 in the
      tolerogenic function of DCs and show that a diminished expression of Blimp-1 in
      DCs can result in aberrant activation of the adaptive immune system with the
      development of a lupus-like serology in a gender-specific manner. This study is
      of particular interest because a polymorphism of Blimp-1 associates with SLE.

PMID- 21948082
TI  - The requirements for natural Th17 cell development are distinct from those of
      conventional Th17 cells.
AB  - CD4(+) T helper 17 (Th17) cells play a critical role in the adaptive immune
      response against extracellular pathogens. Most studies to date have focused on
      understanding the differentiation of Th17 cells from naive CD4(+) T cells in
      peripheral effector sites. However, Th17 cells are present in the thymus. In this
      study, we demonstrate that a population of Th17 cells, natural Th17 cells (nTh17
      cells), which acquire effector function during development in the thymus before
      peripheral antigen exposure, shows preferential usage of T cell receptor Vbeta3.
      nTh17 cells are dependent on major histocompatibility complex (MHC) class II for
      thymic selection, yet unlike conventional CD4(+) T cells, MHC class II expression
      on thymic cortical epithelium is not sufficient for their development, rather
      expression on medullary epithelium is necessary. Differential signaling
      requirements for IL-17 priming further distinguish nTh17 from conventional Th17
      cells. Collectively, our findings define a Th17 population, poised to rapidly
      produce cytokines, that is developmentally distinct from conventional Th17 cells
      and that potentially functions at the interface of innate and adaptive immunity.

PMID- 21948083
TI  - Chronic exposure of gestation rat to sevoflurane impairs offspring brain
      development.
AB  - Recently it was demonstrated that the exposure of the developing brain during the
      period of synaptogenesis to drugs that block NMDA glutamate receptors can trigger
      widespread apoptotic neurodegeneration. Sevoflurane is a new inhalation
      anesthetic agent commonly used in the clinic. Here we address whether sevoflurane
      could induce neurotoxicity in the developing brain. Sevoflurane was administered
      to rats before pregnancy and pregnant rats on embryonic days E6, E10, E14, and
      E18 1MAC for 6 h, and we employed histopathological, immunochemistry,
      semiquantitative RT-PCR, and Western blot to investigate the effect of the
      exposure of pregestation and gestation rats to sevoflurane on the offspring brain
      development. The results showed that the exposure of gestation but not
      pregestation rats to sevoflurane-induced extensive apoptotic neurodegeneration in
      the hippocampus of offspring at P0, P7, and P14, accompanied by altered
      expression of casepase-3, GAP-43, nNOS, NMDAR1, NMDAR2A, and NMDAR2B.
      Furthermore, upregulation of PKCalpha and p-JNK and downregulation of p-ERK and
      FOS protein levels were observed in the hippocampus of offspring at P0, P7, and
      P14 from rats exposed to sevoflurane at gestation, but not pregestation. In
      summary, our data suggest that sevoflurane induces developmental neurotoxicity in
      rats and this may be attributed to the upregulation of PKCalpha and p-JNK and
      downregulation of p-ERK and FOS protein in the hippocampus.

PMID- 21948084
TI  - Acute "upside-down" visual inversion in a patient with multiple sclerosis.
AB  - Visual and oculomotor signs and symptoms are common and well defined in patients
      with multiple sclerosis. On the other hand, the phenomenon of "upside-down"
      reversal of vision is very rare and thus not well known. The physiopathology of
      this phenomenon also has not been well understood. Herein, we present a female
      patient with multiple sclerosis, who developed acute "upside-down" visual
      inversion, and discuss possible mechanisms of this rare phenomenon.

PMID- 21948085
TI  - Check your vestibular skills by reading about the rotational vertebral artery
      syndrome.

PMID- 21948086
TI  - DNA replication induces compositional biases in yeast.
AB  - Asymmetries intrinsic to the process of DNA replication are expected to cause
      differences in the substitution patterns of the leading and the lagging strands
      and to induce compositional biases. These biases have been detected in the
      majority of eubacterial genomes but rarely in eukaryotes. Only in the human
      genome, the activity of a minority of replication origins seems to generate
      compositional biases. In this work, we provide evidence for replication
      associated GC and TA skews in the genomes of two yeast species, Saccharomyces
      cerevisiae and Kluyveromyces lactis, whereas the data for the Schizosaccharomyces
      pombe genome are less conclusive. In contrast with the genomes of Homo sapiens
      and of the majority of eubacteria, the leading strand is enriched in cytosine and
      adenine in both S. cerevisiae and K. lactis. We observed significant variations
      across the interorigin intervals of several substitution rates in the S.
      cerevisiae lineage since its divergence from S. paradoxus. We also found that the
      S. cerevisiae genome is far from compositional equilibrium and that its present
      compositional biases are due to substitution rates operating before its
      divergence from S. paradoxus. Finally, we observed that replication and
      transcription tend to be cooriented in the S. cerevisiae genome, especially for
      genes encoding subunits of protein complexes. Taken together, our results suggest
      that replication-related compositional biases may be a feature of many eukaryotic
      genomes despite the stochastic nature of the firing of replication origins in
      these genomes.

PMID- 21948087
TI  - High incidence of vitamin D deficiency in patients undergoing allogeneic stem
      cell transplantation.

PMID- 21948088
TI  - Inhibition of the Notch-Hey1 axis blocks embryonal rhabdomyosarcoma
      tumorigenesis.
AB  - PURPOSE: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of
      childhood and remains refractory to combined-modality therapy in patients with
      high risk disease. In skeletal myogenesis, Notch signaling prevents muscle
      differentiation and promotes proliferation of satellite cell progeny. Given its
      physiologic role in myogenesis and oncogenic role in other human cancers, we
      hypothesized that aberrant Notch signaling may contribute to RMS tumorigenesis
      and present novel therapeutic opportunities. EXPERIMENTAL DESIGN: Human RMS cell
      lines and tumors were evaluated by immunoblot, IHC, and RT-PCR to measure Notch
      ligand, receptor, and target gene expression. Manipulation of Notch signaling was
      accomplished using genetic and pharmacologic approaches. In vitro cell growth,
      proliferation, and differentiation were assessed using colorimetric MTT and BrdU
      assays, and biochemical/morphologic changes after incubation in differentiation
      promoting media, respectively. In vivo tumorigenesis was assessed using xenograft
      formation in SCID/beige mice. RESULTS: Notch signaling is upregulated in human
      RMS cell lines and tumors compared with primary skeletal muscle, especially in
      the embryonal (eRMS) subtype. Inhibition of Notch signaling using Notch1 RNAi or
      gamma-secretase inhibitors reduced eRMS cell proliferation in vitro. Hey1 RNAi
      phenocopied Notch1 loss and permitted modest myogenic differentiation, while
      overexpression of an activated Notch moiety, ICN1, promoted eRMS cell
      proliferation and rescued pharmacologic inhibition. Finally, Notch inhibition
      using RNAi or gamma-secretase inhibitors blocked tumorigenesis in vivo.
      CONCLUSIONS: Aberrant Notch-Hey1 signaling contributes to eRMS by impeding
      differentiation and promoting proliferation. The efficacy of Notch pathway
      inhibition in vivo supports the development of Notch-Hey1 axis inhibitors in the
      treatment of eRMS.

PMID- 21948090
TI  - Elstera litoralis gen. nov., sp. nov., isolated from stone biofilms of Lake
      Constance, Germany.
AB  - An alphaproteobacterium, strain Dia-1(T), was isolated from algae-dominated
      biofilms on stones from the littoral zone of Lake Constance, Germany. This
      bacterium was isolated after initial enrichment in spent medium obtained after
      growth of a diatom culture. Numerous sugars and some organic acids and alcohols
      served as growth substrates. The bacterium grew slowly, was strictly aerobic but
      microaerophilic, and did not grow in cultures shaken under air. 16S rRNA gene
      sequence analysis indicated that strain Dia-1(T) was distantly related to
      representatives of the genera Azospirillum (90-91% sequence similarity),
      Skermanella (88-89%), Rhodocista (87-88%) and Dongia (88-89% sequence
      similarity). Based on this sequence comparison, on phenotypic characterization
      including substrate utilization patterns, and comparison of cellular fatty acids,
      quinones, polar lipids and polyamines, this isolate was found to be substantially
      different from the genera mentioned above. On the basis of these results, a novel
      genus and species is proposed for this strain. The name Elstera litoralis gen.
      nov., sp. nov. is suggested, with strain Dia-1(T) ( = DSM 19532(T) = LMG
      24234(T)) as the type strain of the type species.

PMID- 21948089
TI  - Complex patterns of altered MicroRNA expression during the adenoma-adenocarcinoma
      sequence for microsatellite-stable colorectal cancer.
AB  - PURPOSE: MicroRNAs are short noncoding RNAs that regulate gene expression and are
      over- or underexpressed in most tumors, including colorectal adenocarcinoma.
      MicroRNAs are potential biomarkers and therapeutic targets and agents, but
      limited information on microRNAome alterations during progression in the well
      known adenoma-adenocarcinoma sequence is available to guide their usage.
      EXPERIMENTAL DESIGN: We profiled 866 human microRNAs by microarray analysis in 69
      matched specimens of microsatellite-stable adenocarcinomas, adjoining precursor
      adenomas including areas of high- and low-grade dysplasia, and nonneoplastic
      mucosa. RESULTS: We found 230 microRNAs that were significantly differentially
      expressed during progression, including 19 not reported previously. Altered
      microRNAs clustered into two major patterns of early (type I) and late (type II)
      differential expression. The largest number (n = 108) was altered at the earliest
      step from mucosa to low-grade dysplasia (subtype IA) prior to major nuclear
      localization of beta-catenin, including 36 microRNAs that had persistent
      differential expression throughout the entire sequence to adenocarcinoma. Twenty
      microRNAs were intermittently altered (subtype IB), and six were transiently
      altered (subtype IC). In contrast, 33 microRNAs were altered late in high-grade
      dysplasia and adenocarcinoma (subtype IIA), and 63 in adenocarcinoma only
      (subtype IIB). Predicted targets in 12 molecular pathways were identified for
      highly altered microRNAs, including the Wnt signaling pathway leading to low
      grade dysplasia. beta-catenin expression correlated with downregulated microRNAs.
      CONCLUSIONS: Our findings suggest that numerous microRNAs play roles in the
      sequence of molecular events, especially early events, resulting in colorectal
      adenocarcinoma. The temporal patterns and complexity of microRNAome alterations
      during progression will influence the efficacy of microRNAs for clinical
      purposes.

PMID- 21948091
TI  - Description of Xenorhabdus magdalenensis sp. nov., the symbiotic bacterium
      associated with Steinernema australe.
AB  - A symbiotic bacterium, strain IMI 397775(T), was isolated from the insect
      pathogenic nematode Steinernema australe. On the basis of 16S rRNA gene sequence
      similarity, this bacterial isolate was shown to belong to the genus Xenorhabdus,
      in agreement with the genus of its nematode host. The accurate phylogenetic
      position of this new isolate was defined using a multigene approach and showed
      that isolate IMI 397775(T) shares a common ancestor with Xenorhabdus doucetiae
      FRM16(T) and Xenorhabdus romanii PR06-A(T), the symbiotic bacteria associated
      with Steinernema diaprepesi and Steinernema puertoricense, respectively. The
      nucleotide identity (less than 97%) between isolate IMI 397775(T), X. doucetiae
      FRM16(T) and X. romanii PR06-A(T) calculated for the concatenated sequences of
      five gene fragments encompassing 4275 nt, several phenotypic traits and the
      difference between the upper temperatures that limit growth of these three
      bacteria allowed genetic and phenotypic differentiation of isolate IMI 397775(T)
      from the two closely related species. Strain IMI 397775(T) therefore represents a
      novel species, for which the name Xenorhabdus magdalenensis sp. nov. is proposed,
      with the type strain IMI 397775(T) ( = DSM 24915(T)).

PMID- 21948092
TI  - Variovorax defluvii sp. nov., isolated from sewage.
AB  - A polyphasic taxonomic study was carried out on 2C1-b(T) and 2C-21, two strains
      isolated from sewage flowing into River Geumho in Korea. Cells of the two strains
      were Gram-negative, non-spore-forming, motile and oval or rod-shaped. Comparative
      16S rRNA gene sequence studies showed a clear affiliation of these two isolates
      with members of the Betaproteobacteria; they were most closely related to
      Variovorax boronicumulans KCTC 22010(T), Variovorax dokdonensis KCTC 12544(T),
      Variovorax ginsengisoli KCTC 12583(T), Variovorax paradoxus ATCC 17713(T) and
      Variovorax soli KACC 11579(T) showing 16S rRNA gene sequence similarities of 97.4
      98.8% with these strains and shared 100% similarity with each other. The genomic
      DNA G+C contents of strains 2C1-b(T) and 2C1-21 were 65.5 and 65.2 mol%,
      respectively. Phenotypic and chemotaxonomic data [Q-8 as the major ubiquinone;
      C(16:0), summed feature 4 (C(16:1)omega7c and/or iso-C(15:0) 2-OH), C(17:0) cyclo
      and summed feature 7 (C(18:1)omega7c and/or omega9t and/or omega12t) as major
      fatty acids] supported the affiliation of strains 2C1-b(T) and 2C-21 to the genus
      Variovorax. Based on evidence derived from this polyphasic analysis, it is
      proposed that strains 2C1-b(T) and 2C1-21 represent a novel species for which the
      name Variovorax defluvii sp. nov. is proposed; the type strain is 2C1-b(T) ( =
      KCTC 12768(T) = JCM 17804(T)).

PMID- 21948093
TI  - Legionella steelei sp. nov., isolated from human respiratory specimens in
      California, USA, and South Australia.
AB  - Legionella-like bacteria were isolated from the respiratory tract of two patients
      in California, USA, and South Australia, but were not thought to cause disease.
      These bacteria, strains F2632 and IMVS-3376(T), were found to have identical
      Legionella macrophage infectivity potentiator (mip) gene sequences and were
      therefore further characterized to determine their genetic and phenotypic
      relatedness and properties. Both of these Gram-negative-staining bacterial
      strains grew on buffered charcoal yeast extract medium, were cysteine auxotrophs
      and made a characteristic diffusible bright yellow fluorescent pigment, with one
      strain making a late appearing colony-bound blue-white fluorescent pigment. The
      optimal in vitro growth temperature was 35  degrees C, with very poor growth at
      37  degrees C in broth or on solid media. There was no growth in human A549 cells
      at either 35 or 37  degrees C, but excellent growth in Acanthamoeba castellani at
      30  degrees C and poorer growth at 35  degrees C. Phylogenetic analysis of these
      bacteria was performed by sequence analysis of 16S rRNA, mip, ribonuclease P,
      ribosomal polymerase B and zinc metalloprotease genes. These studies confirmed
      that the new strains represented a single novel species of the genus Legionella
      for which the name Legionella steelei sp. nov. is proposed. The type strain is
      IMVS-3376(T) ( = IMVS 3113(T) = ATCC BAA-2169(T)).

PMID- 21948094
TI  - Actinomyces weissii sp. nov., isolated from dogs.
AB  - Two Gram-positive, rod-shaped, non-spore-forming bacteria were isolated from the
      oral cavities of two dogs. On the basis of 16S rRNA gene sequence similarities
      both strains were shown to belong to the genus Actinomyces and were most closely
      related to Actinomyces bovis (97.3% and 97.5%, respectively). The polyamine
      profile of the two isolates and Actinomyces bovis DSM 43014(T) was composed of
      spermidine and spermine as the major components. Menaquinone MK-9 was the major
      compound in the quinone system of the two strains and Actinomyces bovis. The
      polar lipid profiles of strains 2298(T) and 4321 were almost identical,
      containing diphosphatidylglycerol as the major compound, and moderate to trace
      amounts of phosphatidylcholine, phosphatidylinositol, phosphatidylinositol
      mannoside, phosphatidylglycerol and several unidentified lipids. A highly similar
      polar lipid profile was detected in Actinomyces bovis DSM 43014(T) supporting the
      affiliation of strains 2298(T) and 4321 to the genus Actinomyces. The typical
      major fatty acids were C(16:0), C(18:0) and C(18:1)omega9c. Fatty acids C(14:0)
      and C(18:2)omega6,9c were found in minor amounts. The results of physiological
      and biochemical analyses revealed clear differences between both strains and the
      most closely related species of the genus Actinomyces. Thus, strains 2298(T) and
      4321 represent a novel species, for which the name Actinomyces weissii sp. nov.,
      is proposed, with strain 2298(T) ( = CIP 110333(T) = LMG 26472(T) = CCM 7951(T) =
      CCUG 61299(T)) as the type strain.

PMID- 21948095
TI  - Labedaea rhizosphaerae gen. nov., sp. nov., isolated from rhizosphere soil.
AB  - A novel actinomycete, designated strain RS-49(T), was isolated from the
      rhizosphere soil of a cliff-associated plant (Peucedanum japonicum Thunb.) in the
      Republic of Korea and subjected to a polyphasic taxonomic study. The results of
      comparative 16S rRNA gene sequence analyses showed that the organism belonged to
      the family Pseudonocardiaceae, suborder Pseudonocardineae and that it was most
      closely related to members of the genera Kibdelosporangium (96.6-97.0% sequence
      similarity), Actinokineospora (96.3-96.7%), Streptoalloteichus (96.2%) and
      Actinophytocola (96.2%). Substrate mycelia were well-developed and whitish or
      pale yellow to strong yellow. Aerial mycelia were branched and fragmented into
      rod-shaped elements. Single spherical spores were produced directly on the
      substrate mycelium. Sporangium-like structures and fragmentation of the substrate
      mycelium were absent. The diagnostic diamino acid in the cell-wall peptidoglycan
      was meso-diaminopimelic acid. The acyl type of the muramic acid residues in the
      peptidoglycan was N-acetylated. Whole-cell sugars were glucose, rhamnose,
      galactose, ribose, mannose, arabinose and xylose. The major menaquinone was MK
      9(H(4)). Small amounts of MK-8 and MK-9(H(2)) were also detected. The polar
      lipids contained diphosphatidylglycerol, phosphatidyldimethylethanolamine,
      phosphatidylglycerol, phosphatidylinositol, an unknown phospholipid and an
      unknown lipid. The predominant fatty acids were iso-C(15:0) and iso-C(16:0). The
      DNA G+C content was 64.2 mol%. The phenotypic and phylogenetic characteristics
      show that strain RS-49(T) can be differentiated from members of all genera in the
      suborder Pseudonocardineae and thus represents a novel species in a new genus for
      which the name Labedaea rhizosphaerae gen. nov., sp. nov. is proposed; the type
      strain of the type species is RS-49(T) ( = KCTC 19662(T) = DSM 45361(T)).

PMID- 21948096
TI  - Cytocentrifugation: a convenient and efficient method for seeding tendon-derived
      cells into monolayer cultures or 3-D tissue engineering scaffolds.
AB  - Tendon and ligament injuries are very common, requiring some 200,000
      reconstructions per year in the USA. Autografting can be used to repair these but
      donor tissue is limited and harvesting leads to morbidity at the graft sites.
      Tissue engineering has been used to grow simple tissues such as skin, cartilage
      and bone and due to their low vascularity and simple structure, tendons should be
      ideal candidates for such an approach. Scaffolds are essential for tissue
      engineering as they provide structure and signals that regulate growth. However,
      they present a physical barrier to cell seeding with the majority of the cells
      congregating at the scaffold surface. To address this we used centrifugation to
      enhance penetration of tendon-derived cells to the centres of 3-D scaffolds. The
      process had no apparent deleterious effects on the cells and both plating
      efficiency and cell distribution improved. After attachment the cells continued
      to proliferate and deposit a collagenous matrix. Scaffold penetration was
      investigated using layers of Azowipes allowing the separation and examination of
      individual leaves. At relatively low g-forces, cells penetrated a stack of 6
      Azowipes leaving cells attached to each leaf. These data suggest that
      cytocentrifugation improves the penetration and homogeneity of tendon derived
      cells in 3-D and monolayer cultures.

PMID- 21948097
TI  - Repeated integration of antibody genes into a pre-selected chromosomal locus of
      CHO cells using an accumulative site-specific gene integration system.
AB  - We previously reported an accumulative site-specific gene integration system
      using Cre recombinase and mutated loxP sites, where a recombinase-mediated
      cassette exchange (RMCE) reaction is repeatable. This gene integration system was
      applied for antibody production using recombinant Chinese hamster ovary (CHO)
      cells. We introduced an exchange cassette flanked by wild-type and mutated loxP
      sites into the chromosome of CHO cells for the establishment of recipient founder
      cells. Then, the donor plasmids including an expression cassette for an antibody
      gene flanked by a compatible pair of loxP sites were prepared. The donor plasmid
      and a Cre expression vector were co-transfected into the founder CHO cells to
      give rise to RMCE in the CHO genome, resulting in site-specific integration of
      the antibody gene. The RMCE procedure was repeated to increase the copy numbers
      of the integrated gene. Southern blot and genomic PCR analyses for the
      established cells revealed that the transgenes were integrated into the target
      site. Antibody production determined by ELISA and western blotting was increased
      corresponding to the number of transgenes. These results indicate that the
      accumulative site-specific gene integration system could provide a useful tool
      for increasing the productivity of recombinant proteins.

PMID- 21948100
TI  - Injection of L-glutamate into the insular cortex produces sleep apnea and
      serotonin reduction in rats.
AB  - PURPOSE: Obstructive sleep apnea (OSA) is primarily characterized by repetitive
      episodes of complete or partial obstruction of airflow during sleep. The neuronal
      and cellular mechanisms underlying this process are not fully understood,
      although the focus of some studies is on putative serotonin (5-HT) mechanisms,
      and serotonergic therapy may be beneficial to OSA patients. This study aimed to
      demonstrate possible changes in 5-HT associated with induction of OSA in a rat
      model. METHODS: Apnea was induced in rats by injection of L-glutamate (L-Glu)
      into the insular cortex. We examined changes in: (1) simultaneous genioglossus
      and diaphragm EMG activity; and (2) peripheral and cerebral levels of 5-HT, by
      histology. RESULTS: Injection of L-glutamate (L-Glu) into the insular cortex
      induced apnea in the rats. L-Glu stimulation of the insular cortex also produced
      significant reductions in plasma 5-HT levels and the expression of 5-HT in the
      brainstem. In addition, lower activity was observed in the GG and a higher
      activity was observed in the diaphragm, as compared to controls. CONCLUSION: Data
      indicate that L-Glu stimulation of the insular cortex simulates the electrical
      activity of the genioglossus muscle and diaphragm in sleep apnea, and contributes
      to reduced peripheral and cerebral 5-HT levels in rats. The results of our study
      suggest that 5-HT may play a role in the pathogenesis of OSA.

PMID- 21948099
TI  - Can the chronic administration of the combination of buprenorphine and naloxone
      block dopaminergic activity causing anti-reward and relapse potential?
AB  - Opiate addiction is associated with many adverse health and social harms, fatal
      overdose, infectious disease transmission, elevated health care costs, public
      disorder, and crime. Although community-based addiction treatment programs
      continue to reduce the harms of opiate addiction with narcotic substitution
      therapy such as methadone maintenance, there remains a need to find a substance
      that not only blocks opiate-type receptors (mu, delta, etc.) but also provides
      agonistic activity; hence, the impetus arose for the development of a combination
      of narcotic antagonism and mu receptor agonist therapy. After three decades of
      extensive research, the federal Drug Abuse Treatment Act 2000 (DATA) opened a
      window of opportunity for patients with addiction disorders by providing
      increased access to options for treatment. DATA allows physicians who complete a
      brief specialty-training course to become certified to prescribe buprenorphine
      and buprenorphine/naloxone (Subutex, Suboxone) for treatment of patients with
      opioid dependence. Clinical studies indicate that buprenorphine maintenance is as
      effective as methadone maintenance in retaining patients in substance abuse
      treatment and in reducing illicit opioid use. With that stated, we must consider
      the long-term benefits or potential toxicity attributed to Subutex or Suboxone.
      We describe a mechanism whereby chronic blockade of opiate receptors, in spite of
      only partial opiate agonist action, may ultimately block dopaminergic activity
      causing anti-reward and relapse potential. While the direct comparison is not as
      yet available, toxicity to buprenorphine can be found in the scientific
      literature. In considering our cautionary note in this commentary, we are
      cognizant that, to date, this is what we have available, and until such a time
      when the real magic bullet is discovered, we will have to endure. However, more
      than anything else this commentary should at least encourage the development of
      thoughtful new strategies to target the specific brain regions responsible for
      relapse prevention.

PMID- 21948101
TI  - Detection of postoperative sleep-disordered breathing using a portable monitoring
      device.
AB  - PURPOSE: Adverse surgical outcomes may occur more frequently in patients with
      sleep-disordered breathing (SDB). Despite this concern, there have been no
      prospective studies using objective measures of postoperative SDB to determine
      the scope of the problem. We designed a prospective study to determine the
      feasibility of identifying SDB in elective postoperative patients by the use of a
      type IV portable monitor (PM). METHODS: Patients >18 years old who presented for
      elective surgery with at least one postoperative hospital night on a non
      monitored unit were enrolled and wore a type IV device that measured nasal flow,
      heart rate, and oxygen saturation on their first postoperative night. Respiratory
      disturbance index (RDI) and oxygen desaturation index (ODI) were generated for
      each patient. RESULTS: Data sufficient for interpretation were collected on
      100/116 patients enrolled. SDB (RDI >=5) was observed in 51% of the study group,
      and 17% had a RDI >15. An elevated ODI >=5 was seen in 42%, while 17% had an ODI
      >=15. Device malfunction occurred in 16% of the study participants. CONCLUSION: A
      type IV PM can be employed in the postoperative setting to detect and gauge the
      severity of SDB.

PMID- 21948104
TI  - The aging process as forward movement and the case for detours and backward
      steps.
AB  - This article focuses on Pruyser's (Pastor Psychol 24:102-118, 1975) view
      presented in his article titled "Aging: Downward, Upward, or Forword?" that the
      later stages of aging are not a downward movement from a higher peak but the
      continuation of a forward movement, and that manifestations of gains as well as
      losses in older adulthood support this view. While expressing agreement with this
      view I draw on Sigmund Freud's discussion of the death instinct in Beyond the
      Pleasure Principle (Freud 1920/1959) to suggest that the later stages of the
      aging process may involve an increase in detours and backward movements.
      Suggesting that these detours and backward steps are potentially beneficial, I
      conclude that Freud provides guidelines for how we may view and evaluate the
      losses and gains that Pruyser identifies as characteristic of the later stages of
      the aging process.

PMID- 21948102
TI  - Immunohistochemical and histomorphometric study of human uvula innervation: a
      comparative analysis of non-snorers versus apneic snorers.
AB  - OBJECTIVE: The objective of this study was to verify a possible correlation
      between the etiology of uvulopalatal ptosis and decrease in palatopharyngeal
      muscle tone, due to a reduction of the number of nerve fibers in surgical
      specimens obtained from snoring patients. DESIGN/SETTING OF THE STUDY: We have
      designed a comparative retrospective, case-control, double-blind,
      immunohistochemical and histomorphometric study of human uvula innervation in 51
      apneic snoring patients who underwent uvulopalatopharyngoplasty (UPPP) and 47
      normal subjects collected in a 5-year-long period in the Departments of
      Otolaryngology of Desio and Forli Hospital, Italy. PATIENTS: Case study was
      chosen in patients who underwent UPPP, variably associated with other
      disobstructive surgical procedures for treatment of obstructive sleep apnea
      syndrome, classified according to current clinical, polysomnographic, endoscopic,
      and imaging criteria. Control subjects were recruited at the Institute of Legal
      Medicine, University of Milan, according to strong inclusion and exclusion
      criteria. The main outcome measure of the study was the number of nerve fibers in
      the patients' uvula evaluated histologically and repeated two times by two
      different people, in all the areas of the specimens. Finally, we correlated the
      area of the histological section with the number of fibers contained therein.
      RESULTS: The number of nerve fibers varied from a minimum of 58 to a maximum of
      163 in normal subjects. In the snoring patient population, the number of nerve
      fibers varied from a minimum of 22 to a maximum of 126 (statistically significant
      difference, p < 0.0001). In conclusion, our results direct toward a clear
      neurogenetic predisposition to uvulopalatal ptosis, marked ab initio by a lower
      set of motor nerve fibers, which may be the initial stage of another subsequent
      morphological and functional abnormality.

PMID- 21948103
TI  - Comparison of printed glycan array, suspension array and ELISA in the detection
      of human anti-glycan antibodies.
AB  - Anti-glycan antibodies represent a vast and yet insufficiently investigated
      subpopulation of naturally occurring and adaptive antibodies in humans. Recently,
      a variety of glycan-based microarrays emerged, allowing high-throughput profiling
      of a large repertoire of antibodies. As there are no direct approaches for
      comparison and evaluation of multi-glycan assays we compared three glycan-based
      immunoassays, namely printed glycan array (PGA), fluorescent microsphere-based
      suspension array (SA) and ELISA for their efficacy and selectivity in profiling
      anti-glycan antibodies in a cohort of 48 patients with and without ovarian
      cancer. The ABO blood group glycan antigens were selected as well recognized
      ligands for sensitivity and specificity assessments. As another ligand we
      selected P(1), a member of the P blood group system recently identified by PGA as
      a potential ovarian cancer biomarker. All three glyco-immunoassays reflected the
      known ABO blood groups with high performance. In contrast, anti-P(1) antibody
      binding profiles displayed much lower concordance. Whilst anti-P(1) antibody
      levels between benign controls and ovarian cancer patients were significantly
      discriminated using PGA (p=0.004), we got only similar results using SA (p=0.03)
      but not for ELISA. Our findings demonstrate that whilst assays were largely
      positively correlated, each presents unique characteristic features and should be
      validated by an independent patient cohort rather than another array technique.
      The variety between methods presumably reflects the differences in glycan
      presentation and the antigen/antibody ratio, assay conditions and detection
      technique. This indicates that the glycan-antibody interaction of interest has to
      guide the assay selection.

PMID- 21948105
TI  - Bedside assessment of passive leg raising effects on venous return.
AB  - OBJECTIVE: Passive leg raising (PLR) provides a reversible fluid-loading
      challenge and can be used to predict fluid responsiveness. The amount of blood
      volume recruited by this maneuver called stressed volume (Vs) is unknown. The
      present study aims to assess the quantitative effects of passive leg raising on
      venous return at bedside. METHODS: We conducted a prospective interventional
      study. Nine mechanically ventilated postoperative cardiac surgery patients with
      preserved left ventricular function were enrolled. Cardiac output (CO) was
      continuously monitored by PiCCOTM via the pulse contour method. Ten second
      intervals of inspiratory breath holding at four plateau pressures (5, 15, 25 and
      35 cm H(2)O) were performed to measure the relationship between blood flow (CO)
      and central venous pressure (CVP). These were used to determine mean systemic
      filling pressure (Pmsf) and Vs. Patients were studied at three successive steps:
      semirecumbent position, after PLR and back in the semirecumbent position after
      volume expansion (VE). RESULTS: Similar to VE, PLR significantly increased Pmsf
      from 19.7 (17.0-22.6) mmHg at baseline to 22.0 (18.5-27.8) mmHg (p <0.05). CO
      increased 11.1% (9.5-20) with PLR and 14.8% (4.2-19.9) with VE. Venous return
      resistance was unchanged throughout the three conditions, whereas the the
      pressure gradient for venous return (Pmsf-CVP) increased during PLR (p = 0.058)
      and during VE (p < 0.05). Baseline circulatory compliance was 1.14 (0.52-2.65) ml
      mm Hg(-1) kg(-1). Vs increased to 3.5 (1.1-3.9) ml kg(-1) with PLR. CONCLUSIONS:
      The effect of transient hemodynamic changes on venous return induced by passive
      leg raising can be directly measured in intensive care patients using inspiratory
      hold procedures. This technique makes quantification of PLR feasible and could be
      used clinically to assess fluid responsiveness.

PMID- 21948106
TI  - On nonstable and stable population momentum.
AB  - This article decomposes total population momentum into two constituent and
      multiplicative parts: "nonstable" momentum and "stable" momentum. Nonstable
      momentum depends on deviations between a population's current age distribution
      and its implied stable age distribution. Stable momentum is a function of
      deviations between a population's implied stable and stationary age
      distributions. In general, the factorization of total momentum into the product
      of nonstable and stable momentum is a very good approximation. The factorization
      is exact, however, when the current age distribution is stable or when observed
      fertility is already at replacement. We provide numerical illustrations by
      calculating nonstable, stable, and total momentum for 176 countries, the world,
      and its major regions. In short, the article brings together disparate strands of
      the population momentum literature and shows how the various kinds of momentum
      fit together into a single unifying framework.

PMID- 21948107
TI  - Explaining the female black-white obesity gap: a decomposition analysis of
      proximal causes.
AB  - There exist remarkably large differences in body weights and obesity prevalence
      between black and white women in the United States; and crucially, these
      differences are a significant contributor to black-white inequalities in health.
      In this article, we investigate the most proximal explanations for the weight
      gap: namely, differences in diet and exercise. More specifically, we decompose
      black-white differences in body mass index and waist-to-height ratio into
      components reflecting black-white differences in energy intake and energy
      expenditure. The analysis indicates that overconsumption is much more important
      than a lack of exercise in explaining the weight gap, which suggests that diet
      interventions will have to play a fundamental role if the weight gap between
      black and white women is to decline.

PMID- 21948108
TI  - Do not go gentle into that good night: the effect of retirement on subsequent
      mortality of U.S. Supreme Court justices, 1801-2006.
AB  - Mortality hazard and length of time until death are widely used as health outcome
      measures and are themselves of fundamental demographic interest. Considerable
      research has asked whether labor force retirement reduces subsequent health and
      its mortality measures. Previous studies have reported positive, negative, and
      null effects of retirement on subsequent longevity and mortality hazard, but
      inconsistent findings are difficult to resolve because (1) nearly all data
      confound retirement with unemployment of older workers, and often, (2)
      endogeneity bias is rarely addressed analytically. To avoid these problems,
      albeit at loss of generalizability to the entire labor force, I examine data from
      an exceptional subgroup that is of interest in its own right: U.S. Supreme Court
      justices of 1801-2006. Using discrete-time event history methods, I estimate
      retirement effects on mortality hazard and years-left-alive. Some substantive and
      methodological considerations suggest models that specify endogenous effects
      estimated by instrumental variables (IV) probit, IV Tobit, and IV regression
      methods. Other considerations suggest estimation by endogenous switching (ES)
      probit and ES regression. Estimates by all these methods are consistent with the
      hypothesis that, on average, retirement decreases health, as indicated by
      elevated mortality hazard and diminished years-left-alive. These findings may
      apply to other occupational groups characterized by high levels of work autonomy,
      job satisfaction, and financial security.

PMID- 21948109
TI  - The comorbidity of anger symptoms with personality disorders in psychiatric
      outpatients.
AB  - OBJECTIVES: Although many psychiatric disorders are "emotional" disorders, no
      disorders exist for which dysfunctional anger is a necessary feature. This study
      examined whether dysfunctional anger could be considered a diagnosis independent
      from Personality Disorders. DESIGN: We analyzed data on 1,158 psychiatric
      outpatients who underwent a semi-structured interview for Axis II disorders and
      ascertained the co-occurrence of dysfunctional anger and Personality Disorders.
      RESULTS: The overlap between dysfunctional anger and all Personality Disorders
      was low. Data analyses showed dysfunctional anger was not well accounted for by
      Axis II diagnoses. CONCLUSIONS: Dysfunctional anger can be viewed by researchers
      and clinicians as an independent diagnostic entity. The implications of these
      results for the diagnosis and treatment of patients with anger symptoms is
      discussed.

PMID- 21948110
TI  - Chromosome analysis using spectral karyotyping (SKY).
AB  - Spectral karyotyping is a novel technique for chromosome analysis that has been
      developed based on the approach of the fluorescence in situ hybridization
      technique. Spectral karyotyping makes it feasible to diagnose a variety of
      diseases, because of its technology in painting each of the 24 human chromosomes
      with different colors. In recent years, it has become possible to adopt the usage
      of spectral karyotyping for research in general clinical practice, and its
      usability has attracted particular attention in the diagnosis of different
      diseases. In this review, we will explain the principle of the spectral
      karyotyping, as well as its specificity and limitation in detecting the genetic
      defects within clinical application by presenting two case reports.

PMID- 21948111
TI  - Bodily pain and coping styles among four geriatric age groups of women.
AB  - No research is available regarding the association between coping styles and
      bodily pain by age-specific sub-groups in non-clinical older populations. To
      address this research gap, we recruited 317 older women (age 55-105, mainly from
      minority ethnic backgrounds) and divided our sample into sub-groups by decade.
      Regression analyses on the total sample and the age group of 65-74 demonstrated
      that denial and venting were inversely related to pain. Findings for the age
      groups 55-64 and 75-84 were non-significant. Among women age 85 or older, seeking
      emotional support was inversely associated with pain, while active coping was
      related to higher pain reports.

PMID- 21948112
TI  - Neurotoxicity of human immunodeficiency virus-1: viral proteins and axonal
      transport.
AB  - Human immunodeficiency virus-1 (HIV) infection of the central nervous system may
      cause a neurological syndrome termed HIV-associated neurocognitive disorder
      (HAND) which includes minor neurocognitive disorders or a more severe form of
      motor and cognitive impairments. Although treatment with highly active
      antiretroviral agents decreases the load of HIV in the brain, the prevalence of
      mild forms of HAND is actually increased due to longer life. Therefore,
      adjunctive and combined therapies must be developed to prevent and perhaps
      reverse the neurologic deficits observed in individuals with HAND. Key to
      developing effective therapies is a better understanding of the molecular and
      cellular mechanisms by which the virus causes this disorder. A number of HIV
      proteins has been shown to be released from HIV-infected cells. Moreover, these
      proteins have been shown to possess neurotoxic properties. This review describes
      new evidence of a direct interaction of the HIV protein gp120 with neurons, which
      might play a role in the etiopathology of HAND.

PMID- 21948113
TI  - Feasibility and benefit of hydroxycarbamide as a long-term treatment for sickle
      cell disease patients: results from the North West London Sickle Cell Disease
      Registry.

PMID- 21948114
TI  - Evaluation of radiation necrosis and malignant glioma in rat models using
      diffusion tensor MR imaging.
AB  - Standard MRI cannot distinguish between radiation necrosis and tumor progression;
      however, this distinction is critical in the assessment of tumor response to
      therapy. In this study, one delayed radiation necrosis model (dose, 40 Gy;
      radiation field, 10 * 10 mm(2); n = 13) and two orthotopic glioma models in rats
      (9L gliosarcoma, n =8; human glioma xenografts, n = 5) were compared using
      multiple diffusion tensor imaging (DTI) indices. A visible isotropic apparent
      diffusion coefficient (ADC) pattern was observed in the lesion due to radiation
      necrosis, which consisted of a hypointense central zone and a hyperintense
      peripheral zone. There were significantly lower ADC, parallel diffusivity, and
      perpendicular diffusivity in the necrotic central zone than in the peripheral
      zone (all P < 0.001). When radiation-induced necrosis was compared with viable
      tumor, radiation necrosis had significantly lower ADC than 9L gliosarcoma and
      human glioma xenografts (both P < 0.01) in the central zone, and significantly
      lower fractional anisotropy than 9L gliosarcoma (P = 0.005) and human glioma
      xenografts (P = 0.012) in the peripheral zone. Histological analysis revealed
      parenchymal coagulative necrosis in the central zone, and damaged vessels and
      reactive astrogliosis in the peripheral zone. These data suggest that qualitative
      and quantitative analysis of the DTI maps can provide useful information by which
      to distinguish between radiation necrosis and viable glioma.

PMID- 21948115
TI  - Crude polysaccharide from an anti-UVB cell clone of Bupleurum scorzonerifolium
      protect HaCaT cells against UVB-induced oxidative stress.
AB  - Bupleurum scorzonerifolium Willd has been found to have a wide range of
      immunopharmacologic functions. We isolated an anti-UVB B. scorzonerifolium cell
      clone and found elevated level of polysaccharides. In this study, we investigated
      the ability of crude polysaccharide (CP) from the anti-UVB B. scorzonerifolium
      cell clone to inhibit UVB-induced photodamage using a human skin keratinocyte
      cell line, HaCaT. Cells were UVB irradiated and then incubated in presence of
      different concentrations of CP. MTT assay showed that the CP did not induce
      cytotoxic effect under 10 mg/mL and after UVB irradiation, CP can inhibit UVB
      induced HaCaT cell death. Decreased reactive oxygen species and lipid
      peroxidation and increased superoxide dismutase activity showed that CP can act
      as a free radical scavenger. Furthermore, CP had a strong protective ability
      against UVB-induced DNA damage. These effects were compared to the crude
      polysaccharide (CP') from normal B. scorzonerifolium callus at concentration of
      20 mg/mL. The portion of crude polysaccharide (CP) from the anti-UVB B.
      scorzonerifolium cell clone was more than 2.5-fold higher than crude
      polysaccharide (CP') from normal B. scorzonerifolium callus. Taken together, the
      protective mechanisms of crude polysaccharide from the anti-UVB B.
      scorzonerifolium cell clone against UVB-induced photodamage occur by the
      inhibition of UVB-induced reactive oxygen species production, lipid peroxidation
      and DNA damage.

PMID- 21948116
TI  - Establishment, characterization and immortalization of a fibroblast cell line
      from the Chinese red belly toad Bombina maxima skin.
AB  - The skin of the amphibian Bombina maxima is rich in biologically active proteins
      and peptides, most of which have mammalian analogues. The physiological functions
      of most of the mammalian analogues are still unknown. Thus, Bombina maxima skin
      may be a promising model to reveal the physiological role of these proteins and
      peptides because of their large capacity for secretion. To investigate the
      physiological role of these proteins and peptides in vitro, a fibroblast cell
      line was successfully established from Bombina maxima tadpole skin. The cell line
      grew to form a monolayer with cells of a uniform shape and abundant rough
      endoplasmic reticulum, which are typical characteristics of fibroblasts. Further
      identification at a molecular level revealed that they strongly expressed the
      fibroblast marker protein vimentin. The chromosome number of these cells is 2n =
      28, and most of them were diploid. Growth property analysis showed that they grew
      well for 14 passages. However, cells showed decreased proliferative ability after
      passage 15. Thus, we tried to immortalize the cells through the overexpression of
      SV40 T antigen. After selecting by G418, cells stably expressed SV40 large T
      antigen and showed enhanced proliferative ability and increased telomerase
      activity. Signal transduction analysis revealed functional p42 mitogen-activated
      protein (MAP) kinase in immortalized Bombina maxima dermal fibroblasts. Primary
      fibroblast cells and the immortalized fibroblast cells from Bombina maxima
      cultured in the present study can be used to investigate the physiological role
      of Bombina maxima skin-secreted proteins and peptides. In addition, the methods
      for primary cell culturing and cell immortalization will be useful for culturing
      and immortalizing cells from other types of amphibians.

PMID- 21948117
TI  - NLRP7 and the genetics of post-molar choriocarcinomas in Senegal.
AB  - Gestational choriocarcinomas are malignant tumors of trophoblastic cells that
      affect 5-25% of women with sporadic hydatidiform moles (HMs) depending on
      countries and studies. Nucleotide binding and oligomerization domain-like
      receptor protein 7 (NLRP7) is a major gene responsible for recurrent HMs and
      recently mutations in this gene have also been shown in 13% of women with
      sporadic, non-recurrent  moles. To investigate the role of NLRP7 in the genetic
      susceptibility for the malignant degeneration of moles, we sequenced its 11 exons
      in 43 Senegalese patients with post-molar choriocarcinomas. We report the
      presence of three novel NLRP7 variants that were found only in patients but not
      in 100 controls from the Senegalese general population, 100 controls from the
      Tunisian general population, and 100 controls from the Canadian population. In
      addition, this analysis revealed significant differences in the frequencies of
      four non-synonymous NLRP7 variants between European and Senegalese controls with
      the biggest difference being for variant G487E present at a minor allele
      frequency of 3.5% in Europeans, 18.1% in Tunisians and 45.6% in Senegalese.
      Comparing human NLRP7 and its paralog, NLRP2, with their mammalian counterparts
      revealed that allele E at position 487 is most likely the ancestral allele that
      was acquired in Africa but driven to low frequencies in Europeans and Asians due
      to migration, population bottlenecks and selective pressures. This study is the
      first attempt to investigate the role of NLRP7 in choriocarcinomas and highlights
      the higher frequencies of NLRP7 variants in the general Senegalese and Tunisian
      populations both known to have higher frequencies of moles and choriocarcinomas.

PMID- 21948119
TI  - Filippo Lussana (1820-1897): from medical practitioner to neuroscience.
AB  - Filippo Lussana's scientific activities are neglected in neurological field. His
      activity could be divided into two phases: as a medical practitioner and the
      academic period, as a clinical neurophysiologist. The focus of his various
      research studies was the central nervous system, including balance disorders (the
      role of the cerebellum and semicircular canals), taste innervation, pain and
      speech disorders (theories of brain localisation). Lussana's clinical method and
      direct dealings with patients laid the groundwork for his subsequent academic
      activities as a neurophysiologist, in Parma and later in Padua. Influenced by
      phrenological theories, he also conducted interesting studies on synaesthesia for
      which he determined a brain site. He contributed to the neurophysiology of taste,
      emphasising the role of the facial nerve. With his study on muscle sense, he also
      joined the debate on the role of the cerebellum in balance, setting the
      foundation for later studies on this organ by Luigi Luciani.

PMID- 21948118
TI  - An ex vivo comparison of the push-out bond strength of a new endodontic filling
      system (Smartseal) and various gutta-percha filling techniques.
AB  - The purpose of this study was to evaluate, ex vivo, the push-out bond strength of
      a new filling material (Smartseal) compared with gutta-percha/AH-26. A total of
      40 extracted single-rooted human teeth were used. After instrumentation using the
      ProTaper rotary system, the root canals were filled as follows: Group 1,
      Smartseal sealer and a 0.06 taper Smartpoint calibrated to apical tip size 30;
      Group 2, Smartseal sealer and an F3 SmartpointPT; Group 3, AH-26 sealer and a
      single F3 ProTaper gutta-percha cone and Group 4, AH-26 sealer and gutta-percha
      using the cold lateral condensation technique. Two successive disk shaped slices
      were cut from each root sample and the bond strength was measured using the push
      out test. Two-way analysis of variance was used for data analysis with the level
      of significance set at 0.05. Statistical analysis revealed no significant
      differences (p > 0.05) between the mean bond strengths of the various groups;
      thus indicating there was no difference in adhesion to dentine between the
      Smartseal system and gutta-percha/AH-26 applied using either the single cone or
      lateral condensation technique.

PMID- 21948120
TI  - Exercise during pregnancy improves maternal glucose screen at 24-28 weeks: a
      randomised controlled trial.
AB  - OBJECTIVE: The influence of an exercise programme performed by healthy pregnant
      women on maternal glucose tolerance was studied. STUDY DESIGN: A physical
      activity (PA, land/aquatic activities) programme during the entire pregnancy
      (three sessions per week) was conducted by a qualified instructor. 83 healthy
      pregnant women were randomly assigned to either an exercise group (EG, n=40) or a
      control (CG, n=43) group. 50 g maternal glucose screen (MGS), maternal weight
      gain and several pregnancy outcomes were recorded. RESULTS: Significant
      differences were found between study groups on the 50 g MGS. Values corresponding
      to the EG (103.8 +/- 20.4 mg/dl) were better than those of the CG (126.9 +/- 29.5
      mg/dl), p=0.000. In addition, no differences in maternal weight gain and no cases
      of gestational diabetes in EG versus 3 in CG (7%) (p>0.05) were found.
      CONCLUSION: A moderate PA programme performed during pregnancy improves levels of
      maternal glucose tolerance.

PMID- 21948121
TI  - Perceived barriers and facilitators to physical activity for children with
      disability: a systematic review.
AB  - AIM: The aim of this systematic review was to investigate the perceived barriers
      and facilitators to physical activity among children with disability. METHODS: 10
      electronic databases were searched from the earliest time available to September
      2010 to identify relevant articles. Articles were included if they examined the
      barriers or facilitators to physical activity for children with disability and
      were written in English. Articles were excluded if they included children with an
      acute, transient or chronic medical condition, examined sedentary leisure
      activities, or societal participation in general. Two reviewers independently
      assessed the search yields, extracted the data and assessed trial quality. Data
      were analysed descriptively. RESULTS: 14 articles met the inclusion criteria.
      Barriers included lack of knowledge and skills, the child's preferences, fear,
      parental behaviour, negative attitudes to disability, inadequate facilities, lack
      of transport, programmes and staff capacity, and cost. Facilitators included the
      child's desire to be active, practising skills, involvement of peers, family
      support, accessible facilities, proximity of location, better opportunities,
      skilled staff and information. CONCLUSION: Personal, social, environmental, and
      policy and programme-related barriers and facilitators influence the amount of
      activity children with disability undertake. The barriers to physical activity
      have been studied more comprehensively than the facilitators.

PMID- 21948122
TI  - Exercise-associated collapse: an evidence-based review and primer for clinicians.
AB  - Exercise-associated collapse (EAC) commonly occurs after the completion of
      endurance running events. EAC is a collapse in conscious athletes who are unable
      to stand or walk unaided as a result of light headedness, faintness and dizziness
      or syncope causing a collapse that occurs after completion of an exertional
      event. Although EAC is perhaps the most common aetiology confronted by the
      medical provider attending to collapsed athletes in a finish-line tent, providers
      must first maintain vigilance for other potential life-threatening aetiologies
      that cause collapse, such as cardiac arrest, exertional heat stroke or exercise
      associated hyponatraemia. Previously, it has been believed that dehydration and
      hyperthermia were primary causes of EAC. On review of the evidence, EAC is now
      believed to be principally the result of transient postural hypotension caused by
      lower extremity pooling of blood once the athlete stops running and the resultant
      impairment of cardiac baroreflexes. Once life-threatening aetiologies are ruled
      out, treatment of EAC is symptomatic and involves oral hydration and a
      Trendelenburg position - total body cooling, intravenous hydration or advanced
      therapies is generally not needed.

PMID- 21948123
TI  - Responsibility of sport and exercise medicine in preventing and managing chronic
      disease: applying our knowledge and skill is overdue.
AB  - BACKGROUND: The rapidly increasing burden of chronic disease is difficult to
      reconcile with the large, compelling body of literature that demonstrates the
      substantial preventive and therapeutic benefits of comprehensive lifestyle
      intervention, including physical activity, smoking cessation and healthy diet.
      Physical inactivity is now the fourth leading independent risk factor for death
      caused by non-communicable chronic disease. Although there have been efforts
      directed towards research, education and legislation, preventive efforts have
      been meager relative to the magnitude of the problem. The disparity between our
      scientific knowledge about chronic disease and practical implementation of
      preventive approaches now is one of the most urgent concerns in healthcare
      worldwide and threatens the collapse of our health systems unless extraordinary
      change takes place. FINDINGS: The authors believe that there are several key
      factors contributing to the disparity. Reductionism has become the default
      approach for healthcare delivery, resulting in fragmentation rather than
      integration of services. This, in turn, has fostered a disease-based rather than
      a health-based model of care and has produced medical school curricula that no
      longer accurately reflect the actual burden of disease. Trying to 'fit'
      prevention into a disease-based approach has been largely unsuccessful because
      the fundamental tenets of preventive medicine are diametrically opposed to those
      of disease-based healthcare. RECOMMENDATION: A clinical discipline within
      medicine is needed to adopt disease prevention as its own reason for existence.
      Sport and exercise medicine is well positioned to champion the cause of
      prevention by promoting physical activity. CONCLUSION: This article puts forward
      a strong case for the immediate, increased involvement of clinical sport and
      exercise medicine in the prevention and treatment of chronic disease and offers
      specific recommendations for how this may begin.

PMID- 21948124
TI  - Perceptual cues in the regulation of exercise performance - physical sensations
      of exercise and awareness of effort interact as separate cues.
AB  - It has been argued that the physical sensations induced by exercise, measured as
      the ratings of perceived exertion (RPE), are distinct from the sense of effort.
      This study aimed to determine whether a new measure of task effort - the Task
      Effort and Awareness (TEA) score - is able to measure sensations distinct from
      those included in the conventional RPE scale. Seven well-trained cyclists
      completed a maximal effort 100 km time trial (TT) and a submaximal trial at 70%
      of the power sustained during the TT (70% TT). Five maximal 1 km sprints were
      included in both trials. Both the RPE related solely to physical sensation (P
      RPE) and the TEA score increased during the TT and were linearly related. During
      the 70% TT, both P-RPE and TEA scores increased, but TEA increased significantly
      less than P-RPE (p<0.001). TEA scores reached maximal values in all 1 km sprints
      in both the maximal TT and 70% TT, whereas the RPE increased progressively,
      reaching a maximal value only in the final 1 km sprints in both the TT and the
      70% TT. These results indicate that the physical sensations of effort measured as
      the P-RPE act as the template regulating performance during exercise and that
      deviation from that template produces an increase in the sense of effort measured
      by the TEA score. Together, these controls ensure that the chosen exercise
      intensity does not threaten bodily homeostasis. Our findings also explain why
      submaximal exercise conducted within the constraints of the template P-RPE does
      not produce any conscious awareness of effort.

PMID- 21948125
TI  - Recommendations of the Polish Society of Sports Medicine on age criteria while
      qualifying children and youth for participation in various sports.

PMID- 21948126
TI  - Degradation of 2,4-D in soils by Fe3O4 nanoparticles combined with stimulating
      indigenous microbes.
AB  - PURPOSE: Degradation of 2,4-dichlorophenoxyacetic acid (2,4-D) in soils by Fe3O4
      nanoparticles combined with soil indigenous microbes was investigated, and the
      effects of Fe3O4 nanoparticles on soil microbial populations and enzyme
      activities were also studied. METHODS: The soils contaminated with 2,4-D were
      treated with Fe3O4 nanoparticles. The microbial populations and enzyme activities
      were analyzed by dilution plate method and chemical assay, respectively, and the
      concentration of 2,4-D in soil was determined by high-performance liquid
      chromatography (HPLC). RESULTS: The results indicated that Fe3O4 nanoparticles
      combined with soil indigenous microbes led to a higher degradation efficiency of
      2,4-D than the treatments with Fe3O4 nanoparticles or indigenous microbes alone.
      The degradation of 2,4-D in soils followed the pseudo first-order kinetic. The
      half-lives of 2,4-D degradation (DT50) of the combined treatments were 0.9, 1.9
      and 3.1 days in a Red soil, Vertisol and Alfisol, respectively, which implied
      that the DT50 of the combination treatments were significantly shorter than that
      of the treatments Fe3O4 nanoparticles or indigenous microbes alone. The effects
      of Fe3O4 nanoparticles on soil microbial populations and enzyme activities were
      also investigated and compared with the alpha-Fe2O3 nanoparticles. The results
      suggested that the alpha-Fe2O3 nanoparticles had only comparatively small effects
      on degradation of 2,4-D in soils, while the Fe3O4 nanoparticles not only degraded
      2,4-D in soils but also increased the soil microbial populations and enzyme
      activities; the maximum increase in enzyme activities were 67.8% (amylase), 53.8%
      (acid phosphatase), 26.5% (catalase) and 38.0% (urease), compared with the
      untreated soil. Moreover, the introduction of Fe3O4 nanoparticles at the
      different dosage resulted in a variable degradation efficiency of 2,4-D in soil.
      CONCLUSION: The method of combining Fe3O4 nanoparticles with indigenous soil
      microbes may offer great benefits for the application of nanotechnology in
      remediation of herbicide contaminated soil.

PMID- 21948127
TI  - Risk posed by chlorinated organic compounds in Abu Qir Bay, East Alexandria,
      Egypt.
AB  - INTRODUCTION: In Egypt, the picture of threats to humans and the environment from
      the exposure to organic pollutants is still incomplete. Thus the objectives of
      this study were to assess the occurrence and distribution of polychlorinated
      biphenyls (PCBs), organochlorine pesticides, and chlorpyrifos in sediments and
      mussels of Abu Qir Bay and their risks for environment and human health.
      MATERIALS AND METHODS: Twenty-three different compounds organochlorines were
      determined in 20 surfacial sediment and 10 mussel samples by gas chromatography
      electron capture detector. A Screening Level Ecological Risk Assessment (SLERA)
      and a Human Health Risk Assessment (HHRA) were performed with the data. RESULTS
      AND DISCUSSION: SigmaDDT (DDT, DDE, DDD) (average concentration 27 ug/kg dw)
      dominated the detected organic pollutants in the sediments, followed by CHLs
      (chlordane, heptachlor, heptachloro epoxide), hexachlorocyclohexane,
      chlorpyrifos, endosulfane, dieldrine, Sigma6 PCBs, aldrine, hexachlorobenzene,
      pentachlorobenzene, methoxychlor, and mirex. In general, concentrations of Sigma6
      PCBs in mussels were higher than their corresponding sediment concentrations
      reflecting their relatively high bioavailability and bioaccumulative potential.
      However, concentrations of the organochlorine pesticides in mussels were lower
      than their corresponding sediment samples. Nevertheless, the SLERA on the bay
      sediments revealed that adverse ecological effects to benthic species are
      expected to occur whereas the HHRA showed that adverse health effects are not
      expected to occur from the consumption of the mussels. CONCLUSIONS: With the help
      of a SLERA, it was possible to indicate which class of chlorinated organic
      compounds is of highest concern to assess and to improve the environmental
      quality of the bay. Monitoring of organochlorines and chlorpyrifos would be
      needed to control the future trend of pollution.

PMID- 21948128
TI  - The effect of laterality on venous thromboembolism formation after peripherally
      inserted central catheter placement.
AB  - PURPOSE: The use of peripherally inserted central venous catheters (PICCs) has
      become widespread in hospital medicine. PICCs are preferentially placed on the
      right side due to anatomic ease of insertion into the superior vena cava.
      However, no data exists examining whether this practice is also protective
      against symptomatic venous thrombosis. The purpose of this study is to assess
      placement of right-sided versus left-sided PICCs and the resulting rates of
      venous thromboembolism (VTE) in a community teaching hospital. METHODS AND
      RESULTS: A retrospective analysis was performed of 798 sequential PICCs placed in
      our community teaching hospital in 2008. Indication for PICC placement,
      laterality of PICC placement, and signs and symptoms leading to ultrasound
      assessment were examined as well as the resulting VTE location. Six hundred and
      seventy two patients had a total of 798 PICCs placed over the course of the year,
      568 of these were right-sided catheters, and 230 were left-sided catheters. Forty
      nine of these patients required 68 Doppler ultrasounds within 30 days of PICC
      placement. Of these ultrasounds, 47 (8.27%) followed right-sided PICCs and 21
      (9.13%) followed left-sided PICCs (OR 0.90, 95% CI 0.52-1.54). VTE events were
      documented in 1.23% of right-sided PICCs and 1.30% of left-sided PICCs (OR 0.94,
      95% CI 0.24-3.68). The overall incidence of this complication was 1.25%. Mean
      time until discovery of the thrombus was 13.6 days. CONCLUSIONS: Laterality of
      PICC placement is not significantly associated with symptomatic VTE formation.
      The overall rate of thrombosis in our study is comparable to that of previous
      studies.

PMID- 21948129
TI  - An unusual case of central venous catheter-related bacteremia.
AB  - Some hemodialysed patients need definitive central venous catheterization. One of
      the main complications is catheter infection, and each infection must be treated.
      We report a case of an unusual cause of central venous catheter (CVC) infection:
      physical examination and catheter opacification demonstrated two pin-holes in the
      catheter. It was possible to salvage the catheter following a treatment regimen
      combining systemic antibiotics, antibiotic locks, fibrinolytics, and removal of a
      catheter segment.

PMID- 21948130
TI  - Prevalence of gastric cancer versus colorectal cancer in Asians with a positive
      fecal occult blood test.
AB  - AIM: Prior studies have reported conflicting results on the yield of
      esophagogastroduodenoscopy (EGD) in patients with a positive fecal occult blood
      test (FOBT). Our aim was to compare the yield between EGD and colonoscopy
      performed in a racially diverse population with a positive FOBT. METHODS: A
      retrospective, cross-sectional study of FOBT positive patients who underwent EGD
      and colonoscopy from January 1, 1999 to November 1, 2008. Endoscopic lesions
      deemed responsible for GI bleeding were identified. RESULTS: Two hundred and
      eighty-seven patients met entry criteria, among which, 63% were Asian and 81%
      were immigrants to the U.S. Forty-four patients had EGD findings deemed
      responsible for a positive FOBT, the most common being esophagitis (25.0%) and
      gastric ulceration (15.9%). Forty-two patients had colonoscopic findings likely
      responsible for a positive FOBT with the most frequent lesion being colonic
      polyps >=9 mm in diameter (76.2%). Prevalence of lower and upper GI tract lesions
      responsible for positive FOBT was similar (14.6% vs. 15.3%, p = 0.2). There was
      no association between a patient reporting upper GI symptoms, or the presence of
      anemia and the detection of upper GI tract lesions on endoscopy. Gastric
      adenocarcinoma (n = 3) was as prevalent as colorectal adenocarcinoma (n = 4). All
      three patients with gastric adenocarcinomas were Asian (prevalence 1.6%).
      CONCLUSIONS: In our racially diverse population evaluated for a positive FOBT,
      gastric adenocarcinoma was as prevalent as colorectal adenocarcinoma; however,
      gastric adenocarcinoma was limited to Asian patients. EGD and colonoscopy should
      be considered in the evaluation of patient populations similar to ours,
      particularly Asian immigrants.

PMID- 21948131
TI  - Occurrence of glyphosate and acidic herbicides in select urban rivers and streams
      in Canada, 2007.
AB  - INTRODUCTION: Public and scientific concern has grown over the last decade in
      Canada over the cosmetic use of pesticides in urban centers. With this in mind, a
      national survey was designed to monitor eight commonly used herbicides in urban
      rivers and streams across Canada. MATERIALS AND METHODS: To coordinate sample
      collections across the country, samples were collected monthly on one of two
      predetermined dates from April to September, 2007 from 19 sites within 16
      watersheds, including 15 sites downstream of urban lands and two reference sites.
      Water samples were also collected approximately three times from each watershed
      during or after precipitation events. All samples were collected using a common
      sampling protocol and all were analyzed using the same analytical laboratories.
      RESULTS AND DISCUSSION: The herbicides 2,4-D, mecoprop, dicamba, glyphosate and
      its major metabolite aminomethylphosphonic acid (AMPA) were most frequently
      detected. Using either herbicide concentrations upstream/downstream of urban
      centers or bromoxynil and clopyralid as indictors of agricultural inputs of
      herbicides to streams, it was clear that environmental concentrations of these
      herbicides downstream of urban areas were linked to urban use in Canada.
      Herbicide concentrations in streams draining urban areas were greater during or
      after significant rainfall events and, with the exception of glyphosate, were
      significantly greater in the Province of Ontario. Herbicide concentrations were
      not correlated to the proportion of the watersheds in urban land use. Also, there
      was no difference in seasonal patterns of herbicide concentrations across urban
      centers when grouped in five geographic areas. None of the herbicide
      concentrations measured exceeded existing Canadian Water Quality Guidelines for
      the protection of aquatic life. CONCLUSIONS: This is the first time a national
      survey of pesticides in urban rivers has been carried out in a consistent fashion
      across Canada. Concentrations of 2,4-D, mecoprop, dicamba, glyphosate, and AMPA
      were linked to urban use and frequently detected in all geographic areas.
      However, geographic differences in concentration suggested differences in usage
      or stream connectivity patterns among urban centers. Some jurisdictions in Canada
      have recently restricted cosmetic use of pesticides and it would be interesting
      to determine whether such restrictions will lead to reduced pesticide
      concentrations in urban streams.

PMID- 21948132
TI  - Indigenous soil bacteria with the combined potential for hydrocarbon consumption
      and heavy metal resistance.
AB  - INTRODUCTION: Transconjugant bacteria with combined potential for hydrocarbon
      utilization and heavy metal resistance were suggested by earlier investigators
      for bioremediation of soils co-contaminated with hydrocarbons and heavy metals.
      The purpose of this study was to offer evidence that such microorganisms are
      already part of the indigenous soil microflora. METHODS: Microorganisms in
      pristine and oily soils were counted on nutrient agar and a mineral medium with
      oil as a sole carbon source, in the absence and presence of either sodium
      arsenate (As V), sodium arsenite (As III) or cadmium sulfate, and characterized
      via 16S rRNA gene sequencing. The hydrocarbon-consumption potential of individual
      strains in the presence and absence of heavy metal salts was measured. RESULTS:
      Pristine and oil-contaminated soil samples harbored indigenous bacteria with the
      combined potential for hydrocarbon utilization and As and Cd resistance in
      numbers up to 4 * 105 CFU g-1. Unicellular bacteria were affiliated to the
      following species arranged in decreasing order of predominance: Bacillus
      subtilis, Corynebacterium pseudotuberculosis, Brevibacterium linens, Alcaligenes
      faecalis, Enterobacter aerogenes, and Chromobacterium orangum. Filamentous forms
      were affiliated to Nocardia corallina, Streptomyces flavovirens, Micromonospora
      chalcea, and Nocardia paraffinea. All these isolates could grow on a wide range
      of pure aliphatic and aromatic hydrocarbons, as sole sources of carbon and
      energy, and could consume oil and pure hydrocarbons in batch cultures. Low As
      concentrations, and to a lesser extent Cd concentrations, enhanced the
      hydrocarbon-consumption potential by the individual isolates. CONCLUSION: There
      is no need for molecularly designing microorganisms with the combined potential
      for hydrocarbon utilization and heavy metal resistance, because they are already
      a part of the indigenous soil microflora.

PMID- 21948133
TI  - Prognostic proof and possible therapeutic mechanisms of herbal medicine in
      patients with metastatic lung and colon cancer.
AB  - Recent studies based on epidemiological models published in this journal and
      elsewhere have demonstrated encouraging patterns suggesting that herbal treatment
      may improve prognosis in advanced colon and lung cancer patients. Various
      problems exist with data from nonrandomized studies of this type, but a strong
      signal of potential positive effect can be seen. The therapeutic mechanisms of
      traditional Chinese medicine in metastatic cancer are discussed against a
      hypothetical, dualistic antiproliferation model and immune-stimulation model of
      tumor progression and regression. Recommendations are made for a strategy to
      demonstrate more conclusively the efficacy of adjunct herbal treatment during
      cancer chemotherapy and for discussions with patients until such time as the
      efficacy trials are completed.

PMID- 21948134
TI  - Role of matrix metalloproteinase 3 gene promoter polymorphism in chronic
      pancreatitis.
AB  - AIM: To study the role of 5A/6A polymorphism of matrix metalloproteinase (MMP-3)
      and their levels in the pathogenesis of chronic pancreatitis (CP). METHODS: One
      hundred and twenty CP patients and an equal number of age and sex-matched healthy
      controls were included in the study. Genotypes were determined for 5A/6A allele
      of MMP-3 gene by allele specific PCR (AS-PCR). The serum MMP-3 levels were
      estimated using sandwich ELISA method. RESULTS: The distribution of the genotypes
      of the 5A/6A polymorphism in both control and study patients was similar (p =
      0.523). Within the disease group, patients with older age, early onset of the
      disease, and addictions such as smoking and alcohol consumption had higher levels
      as compared to those who did not have these features. CONCLUSION: We conclude
      that functional polymorphism of MMP-3 (5A/6A) is not associated with CP. However,
      the higher levels within the disease group indicate its possible role in the
      disease process.

PMID- 21948135
TI  - [Conservative endoscopic retrograde treatment of upper urinary tract tumors:
      retrospective analysis of the last 105 cases].
AB  - INTRODUCTION: Modern flexible ureterorenoscopy allows a retrograde approach to
      urothelial tumors in the upper urinary tract (UUTT) of small dimensions (<1.5
      cm), of low grade and non-invasive. The percutaneous renal approach, although
      more invasive, provides an alternative treatment in case of larger dimension
      neoplasia or difficult retrograde access. The key to the success of endoscopic
      treatment of UUTT is an accurate patient selection. We will bring our experience
      in the treatment of UUTT by conservative endoscopic retrograde treatment.
      MATERIALS AND METHODS: Treatment through endoscopic retrograde approach with
      rigid or flexible ureterorenoscopy has been applied to 105 patients; lesions were
      treated with electrocution or lasers using thin laser fibers type Ho:YAG. We
      evaluated the recurrence rate and the intra- and perioperative complications.
      RESULTS: The recurrence rate was equal to 30.4%. In no case was it necessary to
      recur to blood transfusion; 15% of wall perforations treated in a conservative
      manner occurred without following complications. DISCUSSION: Technological
      innovations, miniaturization and the increase of energy sources, such as fiber
      laser Holmium, have improved the management of endoscopic instruments for upper
      urinary tract tumors. The endoscopic retrograde conservative treatment is
      considered a valid alternative approach in the case of low-stage tumors, low
      grading and small in dimensions.

PMID- 21948136
TI  - The differentiation of humane adult mesenchimal stem cells of bone marrow (hMSC)
      into urothelial cells on bio-engineering support (scaffold): preliminary
      experience of tissue engineering.
AB  - OBJECTIVES: Tissue Engineering can develop scaffolds of Poly-L-Lactic Acid (PLLA)
      for tissue regeneration. The purpose of the present job is to test the
      possibility to seed human adult mesenchymal stem cells on a scaffold supplemented
      with specific grow factors to differentiate them into urothelium. METHODS: The
      Electrospinning technique was used to realize three scaffolds. The first one was
      seeded with urothelial cells, of a primary culture, and Keratinocyte serum free
      medium (KSFM); the second one was seeded with human mesenchymal stem cells (hMSC)
      and a minimum essential medium (aMEM); the third one was seeded with hMSC and
      conditioned medium. RESULTS: Electron microscopy showed scaffolds with cellular
      vitality (>90%) and their cellular proliferation. Moreover, the differentiation
      of hMSC, seeded in conditioned medium, into urothelial cells was demonstrated
      through immunofluorescence assays. CONCLUSIONS: Tissue Engineering can develop
      PLLA scaffolds thanks to the Electrospinning technique. The scaffold is a perfect
      environment for cellular culture and proliferation; a protocol for the
      differentiation of hMSC into urothelial cells is now available.
      Immunofluorescence assays can demonstrate the hMSC differentiation into
      urothelial cells.

PMID- 21948137
TI  - [Retroperitoneal neoformation: case study].
AB  - Retroperitoneal sarcoma represents approximately 12-15% of all sarcomas and
      between 0.2 and 0.5% of all neoplasia. They very rarely metastasize, and the main
      cause of death is local recurrence. Radiotherapy and chemotherapy still do not
      represent valid therapeutic alternatives, therefore radical surgery remains the
      only valid option. We would like to present the following case of a 48-year-old
      male patient. After episodes of right-side renal colic, a 19x16x19 cm mass was
      found, which was palpable in the right quadrants, englobed the right ureter and
      caused ipsilateral hydroureteronephrosis of medium grade. Surgery allowed total
      excision of this neoplasm (which was tenaciously attached to various organs),
      with the sacrifice of the right kidney. The final histological examination on a
      sample taken during surgery confirmed that the neoplasm was a spindle-cell
      sarcoma at an intermediate grade of malignancy. One year after surgery the
      patient is disease free.

PMID- 21948138
TI  - [Fluorescence cystoscopy with hexaminolevulinate: our preliminary experience of
      184 procedures].
AB  - INTRODUCTION: Fluorescence cystoscopy (FC) with hexaminolevulinate (HAL) is a
      recently introduced technique of photodynamic diagnosis (PDD), which aims to
      improve the accuracy of white light cystoscopy (WLC) in the diagnosis of
      superficial bladder tumors (NMIBC), and especially of flat urothelial lesions
      (dysplasia and Ca in situ). We report our experience of a number of cases of WLC
      and FC in a single moment with HAL in the diagnosis and follow-up of NMIBC.
      MATERIALS AND METHODS: The method was applied to 184 selected patients with a
      diagnosis or clinical suspicion - instrumental or early recurrence of bladder
      neoplasia. The lesions found in white light (WL) and/or blue light (FC) were
      sampled separately for histological examination. We evaluated the results in
      terms of diagnostic gain compared to treatment with one WL, false positivity and
      recurrence-free survival compared to historical reference group treated with WL
      only. RESULTS: 26.1% of the lesions were found only by the PDD method. The false
      positivity due to the method adopted was 21.2%. The gain in terms of recurrence
      free survival (compared with historical reference group treated only with WL) was
      22.3% at 12 months and 24.4% at 20 months. It did not show any systemic side
      effects. DISCUSSION: The PDD is a technique that can significantly increase the
      diagnostic accuracy of NMIBC.

PMID- 21948139
TI  - [Uretero-ileal anastomosis in orthotopic neobladder: antireflux versus direct
      techinique].
AB  - OBJECTIVES: We report on the long-term functional results of the orthotopic VIP
      neobladder and compare the outcome of the antireflux technique for ureteral
      implantation versus direct anastomosis. PATIENTS AND METHODS: Between 1998 and
      2009, 84 patients underwent cystoprostatectomy and orthotopic VIP neobladder for
      invasive bladder carcinoma. 96 renal units were reimplanted using the Enine
      Ghoneim antirefluxing technique (group 1). The direct Nesbit end-to-side
      technique for ureteral reimplantation was applied in 72 renal units (group 2).
      The mean follow-up period was 54 months (range, 10-154 months). RESULTS: Of the
      96 renal units who underwent the Enine-Ghoneim technique, 12 (12.5%) had uretero
      ileal anastomotic stricture and 4 (4.1%) had reflux. Of the 72 renal units who
      underwent direct anastomosis, 11 (15.2%) patients had reflux, 2 (2.7%) had
      uretero-ileal anastomotic stricture. The incidence of stricture formation in the
      Enine-Ghoneim technique is significantly higher than direct anastomosis. The
      incidence of reflux in preoperatively dilated ureters was significantly higher in
      direct ureteral anastomosis than antireflux technique. The incidence of stone
      formation, renal scaring and pyelonephritis was comparable in both groups.
      CONCLUSIONS: Direct uretero-ileal anastomosis in orthotopic bladder replacement
      is more reasonable than the Enine-Ghoneim antireflux technique in non-dilated
      ureters. The benefit of the antireflux technique has been overestimated despite
      the frequency of stricture formation.

PMID- 21948140
TI  - [(99m)Tc-MAG3 diuretic renography in assessment of obstructive uropathy. The new
      test F+10SP: a step ahead in the differential diagnosis].
AB  - BACKGROUND: Dilation of the renal pelvis is a problem Urologists have often to
      deal with. One of the key aspects is to clear if the dilation is the consequence
      of an obstruction to the outflow or a simple anatomic variant. Aim of this study
      was to compare two diuretic renographic procedures, F-15 vs the new procedure
      F+10SP (Seated Position) in a group of hydronephrotic patients, in order to
      increase the accuracy in the differential diagnosis between non-obstructive and
      obstructive dilation. MATERIALS AND METHODS: 34 Patients (14 male, 20 female, 18
      71 yrs range), 27 pts having an unilateral hydronephrosis and 7 pts a bilateral
      hydronephrosis diagnosed by ultrasound, were enclosed in the study. They were
      subjected to two 99mTc-MAG3 diuretic renography with furosemide consecutively,
      with different modalities: 1) 40 mg of furosemide were administered IV to patient
      in supine position 15 minutes before tracer injection (Test F-15, by English); 2)
      the new procedure: 20 mg of furosemide were administered IV to patient in Seated
      Position (SP), 10 minutes after tracer injection during dynamic acquisition (Test
      F+10 SP). The average interval between the two tests was 7 days. Two different
      physicians analyzed all the tests. The results were classified as: non
      obstruction (only F+10SP can distinguish between normal and dilated without
      obstruction), obstruction, equivocal and not applicable. RESULTS: Among the 68
      renal units (RU) included in the analysis, the F+10SP test showed normal findings
      in 21 RU (30,8%), dilation without obstruction in 21 RU (30,8%), obstruction in
      25 RU (36.8%) and equivocal result in 1 RU. The F-15 renography showed non
      obstructive results in 35 RU (51.5%), obstruction in 20 RU (29.4%) and equivocal
      findings in 11 RU (16.1%); the test was not applicable in 2 RU (2.9%) due to
      insufficient renal function. Side effects reported for the F-15 renogram were
      hypotension in 1 patient, renal colic in 3 patients, bladder filling in 13
      patients, disruption because of voiding in 4 patients. No complications were
      observed during or after the F+10SP renography. The 20 RU diagnosed with
      obstruction at the F-15 test were considered obstructed also at the F+10SP test.
      CONCLUSIONS: The "equivocal" test rate lowered from 16% for the F-15 test to less
      than 1.5% for the new F+10 SP test. The F+10SP procedure is easy, well tolerated,
      time saving and seems to be a more reliable tool in assessment of obstructive
      uropathy in adults.

PMID- 21948141
TI  - Eutrophication in the Yunnan Plateau lakes: the influence of lake morphology,
      watershed land use, and socioeconomic factors.
AB  - INTRODUCTION: Lakes play an important role in socioeconomic development and
      ecological balance in China, but their water quality has deteriorated
      considerably in recent decades. In this study, we investigated the spatial
      temporal variations of eutrophication parameters (secchi depth, total nitrogen,
      total phosphorus, chemical oxygen demand, chlorophyll-a, trophic level index, and
      trophic state index) and their relationships with lake morphology, watershed land
      use, and socioeconomic factors in the Yunnan Plateau lakes. DISCUSSION: Results
      indicated that about 77.8% of lakes were eutrophic according to trophic state
      index. The plateau lakes showed spatial variations in water quality and could be
      classified into high-nutrient and low-nutrient groups. However, because
      watersheds were dominated by vegetation, all eutrophication parameters except
      chlorophyll-a showed no significant differences between the wet and dry seasons.
      Lake depth, water residence time, volume, and percentage of built-up land were
      significantly related to several eutrophication parameters. Agricultural land use
      and social-economic factors had no significant correlation with all
      eutrophication parameters. Stepwise regression analyses demonstrated that lake
      depth and water residence time accounted for 73.8% to 87.6% of the spatial
      variation of single water quality variables, respectively. Redundancy analyses
      indicated that lake morphology, watershed land use, and socioeconomic factors
      together explained 74.3% of the spatial variation in overall water quality. The
      results imply that water quality degradation in the plateau lakes may be mainly
      due to the domestic and industrial wastewaters. This study will improve our
      understanding of the determinants of lake water quality and help to design
      efficient strategies for controlling eutrophication in the plateau region.

PMID- 21948142
TI  - Degradation of 1,4-dioxane using advanced oxidation processes.
AB  - INTRODUCTION: In the nuclear industry 1,4-dioxane is used as a solvent in liquid
      scintillation technique for measuring low-energy beta-emitters such as 3H or C14
      in aqueous media. Improper disposal of 1,4-dioxane can contaminate the ground and
      surface waters. Conventional wastewater treatment processes like chemical
      treatment, air stripping, carbon adsorption, and biological treatment are
      ineffective for the degradation of 1,4-dioxane. METHODS: In the present study,
      the kinetics of degradation of 1,4-dioxane using advanced oxidation processes
      viz., H2O2 alone, Fe(II) + H2O2, UV (15 W) + H2O2, UV (15 W) + Fe(II) + H2O2, US
      (130 KHz) + Fe(II) + H2O2, and sunlight + Fe(II) + H2O2 at pH 3.0 was
      investigated. The optimization of Fe (II) for the processes using Fe (II) + H2O2
      was carried out. CONCLUSIONS: The kinetics of degradation using sunlight + Fe
      (II) + H2O2 was found to be fastest when compared to the other processes. The
      degradation was found to follow first-order kinetics. Formation of acidic
      intermediates was suspected from the observed pH changes during the degradation
      processes.

PMID- 21948143
TI  - Distribution and sources of polycyclic aromatic hydrocarbons (PAHs) in sediment
      from the upper reach of Huaihe River, East China.
AB  - INTRODUCTION: To assess the status of polycyclic aromatic hydrocarbons (PAHs)
      contamination in sediments from the upper reach of Huaihe River, East China, 16
      surface sediment samples were collected in March 2007 and analyzed for 16 USEPA
      priority PAHs. RESULTS AND DISCUSSION: The results indicated that the total
      concentrations of 16 PAHs (?PAHs) were 95.2-877.5 MUg kg(-1) dry weight (dw) with
      a mean value of 370.8 MUg kg(-1) dw for the main stream, 85.7-935.2 MUg kg(-1) dw
      with a mean concentration of 480.7 MUg kg(-1) dw for tributaries, and 144.8-303.2
      MUg kg(-1) dw with an average concentration of 224.0 MUg kg(-1) dw for lakes.
      PAHs pollution was closely related to sewage input and industrial activities.
      Furthermore, the distribution of PAHs in sediments from the main stream indicated
      that the input of tributaries was an important factor for Huaihe River. In
      comparison to a worldwide survey of sedimentary PAHs concentrations, PAHs
      pollution in Huaihe River sediments was ranked as low to moderate. The dominant
      compounds in surface sediment samples were four-ring and five-ring PAH compounds.
      CONCLUSION: Selected PAH ratios suggested that PAHs mainly came from the
      contamination of pyrogenic processes, such as coal and biomass combustion. Risk
      assessment indicated that PAHs in sedimentary environment in the upper reach of
      Huaihe River may cause mild toxic effects but would not cause immediate
      biological effects.

PMID- 21948145
TI  - Biopsy procedures for molecular tissue diagnosis of invasive fungal infections.
AB  - The incidence of invasive fungal infections (IFI) has increased substantially and
      the epidemiology has changed dramatically in recent years. Candida albicans is
      still most important, but non-albicans species, Aspergillus species,
      Glomeromycota (formerly Zygomycetes) and Fusarium species are an increasing cause
      of IFIs. Due to this growing diversity, the identification of the causative
      organism to genus and species level is important to perform best and adequate
      treatment. The early, sensitive and specific detection of IFIs remains
      challenging and current conventional methods are limited. The golden standard for
      the definite diagnosis of proven pulmonary infection remains either
      histopathologic, cytopathologic or direct tissue examination. Invasive procedures
      are necessary to obtain reliable specimens and biopsies may be taken
      percutaneously, bronchoscopically, via open surgery or via video-assisted
      thorascopic surgery. Molecular methods, like PCR or in situ hybridization, are a
      promising diagnostic tool for rapid and reliable species identification and
      should be performed in addition to microscopic examination and culture to
      increase the sensitivity for the diagnosis of IFI. Combining culture, microscopy,
      serology, and PCR in lung tissues and/or bronchial samples will increase the
      diagnostic yield by 99%. Here, we give an overview of biopsy procedures for
      molecular tissue diagnosis of IFI.

PMID- 21948144
TI  - In situ stabilization of trace metals in a copper-contaminated soil using P
      spiked Linz-Donawitz slag.
AB  - PURPOSE: A former wood exploitation revealing high Cu and As concentration of the
      soils served as a case study for assisted phytoextraction. METHOD: P-spiked Linz
      Donawitz (LD) slag was used as a soil additive to improve physico-chemical soil
      properties and in situ stabilize Cu and other trace metals in a sandy Cu
      contaminated soil (630 mg kg-1 soil). The LD slag was incorporated into the
      contaminated soil to consist four treatments: 0% (T1), 1% (T2), 2% (T3), and 4%
      (T4). A similar uncontaminated soil was used as a control (CTRL). After a 1-month
      reaction period, potted soils were used for a 2-week growth experiment with dwarf
      beans. RESULTS: Soil pH increased with the incorporation rate of LD slag.
      Similarly the soil electrical conductivity (EC, in millisiemens per centimetre)
      is ameliorated. Bean plants grown on the untreated soil (T1) showed a high
      phytotoxicity. All incorporation rates of LD slag increased the root and shoot
      dry weight yields compared to the T1. The foliar Ca concentration of beans was
      enhanced for all LD slag-amended soil, while the foliar Mg, K, and P
      concentrations were not increased. Foliar Cu, Zn, and Cr concentrations of beans
      decreased with the LD slag incorporation rate. CONCLUSIONS: P-spiked LD slag
      incorporation into polluted soil allow the bean growth and foliar Ca
      concentration, but also to reduce foliar Cu concentration below its upper
      critical value avoiding an excessive soil EC and Zn deficiency. This dual effect
      can be of interest for soil remediation at larger scale.

PMID- 21948146
TI  - Beliefs about tobacco, health, and addiction among adults in Cambodia: findings
      from a national survey.
AB  - There remains a very high rate of smoked and smokeless tobacco use in the Western
      Pacific Region. The most recent findings from national adult tobacco surveys
      indicate that very few daily users of tobacco intend to quit tobacco use. In
      Cambodia, a nation that is predominantly Buddhist, faith-based tobacco control
      programs have been implemented where, under the fifth precept of Buddhism that
      proscribes addictive behaviors, monks were encouraged to quit tobacco and temples
      have been declared smoke-free. In the present study, we included items on a large
      national tobacco survey to examine the relation between beliefs (faith-based,
      other) about tobacco, health, and addiction among adults (18 years and older). In
      a stratified, multistage cluster sample (n=13,988) of all provinces of Cambodia,
      we found that (1) 88-93% believe that Buddhist monks should not use tobacco, buy
      tobacco, or be offered tobacco during a religious ceremony; (2) 86-93% believe
      that the Wat (temple) should be a smoke-free area; (3) 93-95% believe that
      tobacco is addictive in the same way as habits (opium, gambling, alcohol) listed
      under the fifth precept of Buddhism; and (4) those who do not use tobacco are
      significantly more likely to cite a Buddhist principle as part of their anti
      tobacco beliefs. These data indicate that anti-tobacco sentiments are highly
      prevalent in the Buddhist belief system of Cambodian adults and are especially
      evident among non-users of tobacco. Our findings indicate that faith-based
      initiatives could be an effective part of anti-tobacco campaigns in Cambodia.

PMID- 21948147
TI  - Bereavement and transformation: a psycho-spiritual and post-traumatic growth
      perspective.
AB  - In the aftermath of loss, it is not uncommon for individuals to disclose psycho
      spiritual experiences that lead to personal changes and psychological growth.
      This article argues for and outlines a broad conceptual framework that captures
      and acknowledges the significance of these subjective experiences. The model
      synthesises and integrates two approaches to healthy growth: Lawrence Calhoun and
      Richard Tedeschi's post-traumatic growth model and Stanislav and Christina Grof's
      model of psycho-spiritual transformation. A rationale for a broader model and
      underpinning theory is briefly discussed, and their shared understandings about
      the human potential for growth in the struggle through loss are explored. 

PMID- 21948149
TI  - Prevalence of defaecatory disorders in morbidly obese patients before and after
      bariatric surgery.
AB  - BACKGROUND: The prevalence of obesity is increasing worldwide and has lately
      reached epidemic proportions in western countries. Several epidemiological
      studies have consistently shown that both overweight and obesity are important
      risk factors for the development of various functional defaecatory disorders
      (DDs), including faecal incontinence and constipation. However, data on their
      prevalence as well as effectiveness of bariatric surgery on their correction are
      scant. The primary objective of this study was to estimate the effect of morbid
      obesity on DDs in a cohort of patients listed for bariatric surgery. We also
      evaluated preliminary results of the effects of sleeve gastrectomy on these
      disorders. PATIENTS AND METHODS: A questionnaire-based study was proposed to
      morbidly obese patients having bariatric surgery. Data included demographics,
      past medical, surgical and obstetrics histories, as well as obesity related co
      morbidities. Wexner Constipation Score (WCS) and the Faecal Incontinence Severity
      Index (FISI) questionnaires were used to evaluate constipation and incontinence.
      For the purpose of this study, we considered clinically relevant a WCS >=5 and a
      FISI score >=10. The same questionnaires were completed at 3 and 6 months follow
      up after surgery. RESULTS: A total of 139 patients accepted the study and 68
      underwent sleeve gastrectomy and fully satisfied our inclusion criteria with a
      minimum follow-up of 6 months. Overall, mean body mass index (BMI) at listing was
      47 +/- 7 kg/m(2) (range 35-67 kg/m(2)). Mean WCS was 4.1 +/- 4 (range 0-17),
      while mean FISI score (expressed as mean+/-standard deviation) was 9.5 +/- 9
      (range 0-38). Overall, 58.9% of the patients reported DDs according to the above
      mentioned scores. Twenty-eight patients (20%) had WCS >=5. Thirty-five patients
      (25%) had a FISI >=10 while 19 patients (13.7%) reported combined abnormal
      scores. Overall, DDs were more evident with the increase of obesity grade: Mean
      BMI decreased significantly from 47 +/- 7 to 36 +/- 6 and to 29 +/- 4 kg/m(2)
      respectively at 3 and 6 months after surgery (p < 0.0001). According to the BMI
      decrease, the mean WCS decreased from 3.7 +/- 3 to 3.1 +/- 4 and to 1.6 +/- 3
      respectively at 3 and 6 months (p = 0.02). Similarly, the FISI score decreased
      from 10 +/- 8 to 3 +/- 4 and to 1 +/- 2 respectively at 3 and 6 months (p =
      0.0001). CONCLUSIONS: Defaecatory disorders are common in morbidly obese
      patients. The risk of DDs increases with BMI. Bariatric surgery reduces DDs,
      mainly faecal incontinence, and these findings correlated with BMI reduction.

PMID- 21948148
TI  - Different features of complications with Billroth-I and Roux-en-Y reconstruction
      after laparoscopy-assisted distal gastrectomy.
AB  - BACKGROUND: This study investigated differences in the features of postoperative
      complications between Billroth-I (B-I) and Roux-en-Y (R-Y) reconstructions after
      laparoscopy-assisted distal gastrectomy (LADG) for early gastric cancer. MATERIAL
      AND METHODS: The study included 424 patients who underwent LADG for cT1, cN0
      gastric cancer. Patient characteristics, surgical outcomes, postoperative
      complications including severity assessment using the Clavien-Dindo
      classification, and risk factors related to postoperative complications were
      analyzed. RESULTS: B-I and R-Y were performed in 329 and 95 patients,
      respectively. Total time in hospital was longer in R-Y (15.2 +/- 10.5 days) than
      in B-I (12.8 +/- 6.4 days; P = 0.034). The incidence of severe complications was
      higher in R-Y (13.7%) than in B-I (5.2%; P = 0.009). Three cases of internal
      hernia and three cases of duodenal stump leakage were observed in R-Y. Univariate
      analysis revealed the method of reconstruction was a risk factor for severe
      postoperative complications after LADG (P = 0.006). CONCLUSIONS: The features of
      postoperative complications are quite different between B-I and R-Y after LADG.
      Complications after R-Y were more severe than those after B-I. To avoid these
      severe complications in R-Y, it is necessary to understand these different
      features.

PMID- 21948150
TI  - Preparation of heparin/heparan sulfate oligosaccharides with internal N
      unsubstituted glucosamine residues for functional studies.
AB  - The rare N-unsubstituted glucosamine (GlcNH (3)(+)) residues in heparan sulfate
      (HS) have important biological and pathophysiological roles. However, it is
      difficult to prepare naturally-occuring, GlcNH(3)(+)-containing oligosaccharides
      from HS because of their low abundance, as well as the inherent problems in both
      excising and identifying them. Therefore, the ability to chemically generate a
      series of structurally-defined oligosaccharides containing GlcNH(3)(+) residues
      would greatly contribute to investigating their natural role in HS. In this
      study, a series of heparin/HS oligosaccharides, from dp6 up to dp16 in length
      that possess internal GlcNH(3)(+) residues were prepared by a combination of
      chemical modification and heparinase I digestion. Purification and structural
      analysis of the major species derived from the octa- to dodeca-saccharide size
      fractions indicated the introduction of between 1 and 3 internal GlcNH(3)(+)
      residues per oligosaccharide. In addition, a GlcNH(3)(+) residue was selectively
      introduced into an internal position in a tetrasaccharide species by direct
      chemical modification. This selectivity has potential as an alternative procedure
      for preparing internally-modified oligosaccharides of various lengths. The
      utility of such oligosaccharides was demonstrated by a comparison of the binding
      of three different tetrasaccharide species containing 0, 1 and 2 free amino
      groups to the NK1 truncated variant of hepatocyte growth factor/scatter factor.

PMID- 21948151
TI  - A new methodological sequence to expand and transdifferentiate human umbilical
      cord blood derived CD133+ cells into a cardiomyocyte-like phenotype.
AB  - Transplantation of antigenic-separated stem cells for human cardiovascular
      diseases such as myocardial infarction needs to be supported by experimental
      studies that allow refinement of the procedure. In this study we investigated
      optimising a protocol for the expansion and subsequent differentiation of human
      umbilical cord blood (HUCB) derived CD133(+) stem cells into a cardiomyocyte-like
      lineage. CD133(+) cells from HUCB were selected first by immunomagnetic
      separation and their purity was confirmed by flow cytometry analysis. For
      expansion and differentiation we developed a novel culture medium recipe that
      involves sequential signalling factors. Briefly, CD133(+) cells were expanded for
      6 days under optimal serum-free conditions in combination with fibronectin and
      assessed by microscopy and AlamarBlue proliferation assay. Expanded CD133(+)
      cells were then plated in a cardiac differentiation promoting medium and cultured
      up to 4 weeks. With this protocol HUCB-CD133(+) cells can be regularly expanded
      in serum-free medium to obtain recovery and growth in vitro up to 6 folds. The
      addition of recombinant human thrombopoietin to the remaining factors of the
      expanding medium was associated with larger cell expansion. Expanded UCB CD133(+)
      cells showed a cardiomyocyte-like phenotype following differentiation in vitro
      through expressing intracellular cardiac specific markers including cardiac
      specific alpha-actin, myosin heavy chain and troponin I. This change in phenotype
      was associated with the expression of cardiac-specific transcription factors Gata
      4 and MEF2C. In addition, the change in phenotype was associated with an
      upregulation of nuclear receptor transcription factors including PPAR alpha,
      PPARgamma, RXR alpha and RXRbeta. We believe our protocol represents a
      significant advancement and overcome the technical hurdle of deriving
      cardiomyogenic-like cells from HUCB CD133(+) stem cells. In addition, it has the
      required attributes of simplicity and consistency. This will permit more robust
      manipulation of these cells towards better engraftment and repair in patients
      with myocardial infarction.

PMID- 21948152
TI  - Integrating heterogeneous gene expression data for gene regulatory network
      modelling.
AB  - Gene regulatory networks (GRNs) are complex biological systems that have a large
      impact on protein levels, so that discovering network interactions is a major
      objective of systems biology. Quantitative GRN models have been inferred, to
      date, from time series measurements of gene expression, but at small scale, and
      with limited application to real data. Time series experiments are typically
      short (number of time points of the order of ten), whereas regulatory networks
      can be very large (containing hundreds of genes). This creates an under
      determination problem, which negatively influences the results of any inferential
      algorithm. Presented here is an integrative approach to model inference, which
      has not been previously discussed to the authors' knowledge. Multiple
      heterogeneous expression time series are used to infer the same model, and
      results are shown to be more robust to noise and parameter perturbation.
      Additionally, a wavelet analysis shows that these models display limited noise
      over-fitting within the individual datasets.

PMID- 21948153
TI  - Tunable kinetic proofreading in a model with molecular frustration.
AB  - In complex systems, feedback loops can build intricate emergent phenomena, so
      that a description of the whole system cannot be easily derived from the
      properties of the individual parts. Here, we propose that inter-molecular
      frustration mechanisms can provide non-trivial feedback loops which can develop
      non-trivial specificity amplification. We show that this mechanism can be seen as
      a more general form of a kinetic proofreading (KP) mechanism, with an interesting
      new property, namely the ability to tune the specificity amplification by
      changing the reactants concentrations. This contrasts with the classical KP
      mechanism in which specificity is a function of only the reaction rate constants
      involved in a chemical pathway. These results are also interesting because they
      show that a wide class of frustration models exists that share the same
      underlining KP mechanisms, with even richer properties. These models can find
      applications in different areas such as evolutionary biology, immunology, and
      biochemistry.

PMID- 21948154
TI  - Is alexithymia related to colon cancer? A survey of patients undergoing a
      screening colonoscopy examination.
AB  - The current study examined whether alexithymia is involved in colon cancer as has
      been found in breast and uterine cancer research. The TAS-20 was administered
      before examination to patients who underwent colon cancer screening. Histological
      data were obtained from the biopsies. Gender, age, education, smoking and
      drinking habits, and personal and family histories of neoplastic colonic disease
      were controlled for in the analysis. Both adenoma and adenocarcinoma patients had
      higher TAS-20 scores than negative cases, and both high and intermediate levels
      of alexithymia were implicated. Difficulty identifying feelings and externally
      oriented thinking were the most prominent facets related to the disease process.

PMID- 21948155
TI  - PI3K, Erk signaling in BMP7-induced epithelial-mesenchymal transition (EMT) of PC
      3 prostate cancer cells in 2- and 3-dimensional cultures.
AB  - We reported previously that bone morphogenetic protein 7 (BMP7) could induce
      epithelial-mesenchymal transition (EMT) in PC-3 prostate cancer cells grown in
      tissue culture plates. In this study, we examined BMP7-induced morphological and
      molecular expression changes that are characteristic of EMT using these cells
      under both two- (2D) and three-dimensional (3D) culture conditions. Filamentous
      outgrowths from spheroid structures that were formed from PC-3 cells in 3D
      cultures were strikingly evident when the spheroids were exposed to extracellular
      BMP7. This morphological change in 3D was accompanied by down-regulation of E
      cadherin, which is an essential adhesion molecule for the integrity of epithelial
      phenotype. Invasiveness of the cancer cells was significantly enhanced with BMP7
      treatment along with activation and up-regulation of proteases such as MMP1,
      MMP13, and urokinase plasminogen activator. Signal transduction of EMT conversion
      was examined by the use of certain pathway-specific inhibitors. Of the chemical
      inhibitors tested, inhibitors of PI3 kinase and Erk were found to suppress BMP
      induced morphological changes both in 2D and 3D conditions. These results suggest
      that, besides the Smad signaling pathways, BMP-induced activation of PI3K and Erk
      contribute to EMT morphologic conversion of the PC-3 prostate cancer cells.
      Together, the results support the notion that the complexity of EMT may be better
      evaluated in terms of both spatial and temporal processes in 3D cell culture
      models that are physiologically more relevant than the cell growth in tissue
      culture plates.

PMID- 21948157
TI  - Assays for determination of protein concentration.
AB  - Biochemical analysis of proteins relies on accurate quantitation of protein
      concentration. This appendix describes how to perform commonly used protein
      assays, e.g., Lowry, Bradford, BCA, and UV spectroscopic protein assays. The
      primary focus of the appendix is assay selection, emphasizing sample and buffer
      compatibility. Protein assay standard curves and data processing fundamentals are
      discussed in detail. This appendix also details high-throughput adaptations of
      the commonly used protein assays, and also contains a protocol for BCA assay of
      total protein in SDS-PAGE sample buffer that is used for equal loading of SDS
      PAGE gels, which is reliable, inexpensive, and quick.

PMID- 21948158
TI  - Purification and concentration of DNA from aqueous solutions.
AB  - This unit presents basic procedures for manipulating solutions of single- or
      double-stranded DNA through purification and concentration steps. These
      techniques are useful when proteins or solute molecules need to be removed from
      aqueous solutions, or when DNA solutions need to be concentrated. The Basic
      Protocol, using phenol extraction and ethanol (or isopropanol) precipitation, is
      appropriate for purification of DNA from small volumes (<0.4 ml) at
      concentrations lower than 1 mg/ml. Three support protocols outline methods to
      buffer the phenol used in extractions, concentrate DNA using butanol, and extract
      residual organic solvents with ether, respectively. An alternative to these
      methods is nucleic acid purification using glass beads, and this technique is
      also presented. These protocols may also be used for purifying RNA. The final two
      alternate protocols are used for concentrating RNA and extracting and
      precipitating DNA from larger volumes and from dilute solutions, and for removing
      low-molecular-weight oligonucleotides and triphosphates.

PMID- 21948159
TI  - Electrophysiology of airway nerves.
AB  - Several different electrophysiological approaches have been used to study the
      pharmacology of the afferent, central, and efferent nervous systems in airways.
      This unit describes electrophysiological methods used to study nerves in these
      pathways and includes: (1) extracellular recording of afferent nerve activity in
      vivo and from the isolated airway in vitro, (2) intracellular and patch clamp
      recording of identified airway sensory neurons, (3) patch clamp recording of
      secondary afferent central nervous system neurons, (4) in vitro and in vivo
      intracellular recording of intact parasympathetic ganglionic neurons, and (5)
      patch recordings of dissociated parasympathetic ganglionic neurons.

PMID- 21948160
TI  - Murine and canine models of appendicular osteosarcoma.
AB  - Appendicular osteosarcoma (OSA) is a primary bone sarcoma affecting humans during
      their second decade of life. Despite aggressive surgical and chemotherapeutic
      interventions, 30% of patients will experience progressive metastatic disease
      within 5 years of diagnosis. Understanding the biology of pediatric OSA and
      potential targets for therapeutic development remains an area of focus for both
      basic scientists and clinical oncologists. The identification and study of
      relevant comparative tumor models in mice and canines may allow for a better
      understanding of OSA biology, and permit the rapid investigation of novel
      therapeutic strategies for managing this metastatic bone sarcoma. This unit
      provides a protocol for using an orthotopic, syngeneic murine model of
      appendicular OSA as an investigative tool for the study of OSA biology.
      Additionally, the comparative relevance of spontaneously occurring appendicular
      OSA in canines for the study of pediatric bone sarcomas is discussed.

PMID- 21948161
TI  - Carcinogen-induced animal models of head and neck squamous cell carcinoma.
AB  - This unit provides two models of oral carcinogenesis (hamster cheek pouch and rat
      tongue), as well as more simple procedures to induce squamous cell carcinomas
      (SCCs) in mouse skin. The most significant usage of these models has been their
      application in studying the molecular pathology of the genesis and multi-step
      progression of tobacco-associated SCC. Nevertheless, these protocols have been
      used frequently as in vivo bioassays to demonstrate the chemopreventive and, to a
      lesser extent, the chemotherapeutic effects of numerous compounds. Several
      examples, using four different carcinogenesis protocols, are presented with
      detailed steps on how to elicit squamous lesions and when and how to apply test
      compounds that could have either cancer chemopreventive or chemotherapeutic
      effects.

PMID- 21948156
TI  - The role of DNA exonucleases in protecting genome stability and their impact on
      ageing.
AB  - Exonucleases are key enzymes involved in many aspects of cellular metabolism and
      maintenance and are essential to genome stability, acting to cleave DNA from free
      ends. Exonucleases can act as proof-readers during DNA polymerisation in DNA
      replication, to remove unusual DNA structures that arise from problems with DNA
      replication fork progression, and they can be directly involved in repairing
      damaged DNA. Several exonucleases have been recently discovered, with potentially
      critical roles in genome stability and ageing. Here we discuss how both intrinsic
      and extrinsic exonuclease activities contribute to the fidelity of DNA
      polymerases in DNA replication. The action of exonucleases in processing DNA
      intermediates during normal and aberrant DNA replication is then assessed, as is
      the importance of exonucleases in repair of double-strand breaks and interstrand
      crosslinks. Finally we examine how exonucleases are involved in maintenance of
      mitochondrial genome stability. Throughout the review, we assess how nuclease
      mutation or loss predisposes to a range of clinical diseases and particularly
      ageing.

PMID- 21948162
TI  - Orthotopic model of human pancreatic ductal adenocarcinoma and cancer cachexia in
      nude mice.
AB  - Pancreatic ductal adenocarcinoma (PDAC) represents the fourth leading cause of
      cancer-related deaths in the United States, with a 5-year survival rate of only
      2% to 10%. This tumor is aggressive, often metastasizing to distant sites (liver,
      lung, and adjacent intestines) by the time of diagnosis. Treatment options are
      limited, and the disease carries a grave prognosis for most patients. An
      orthotopic model of human PDAC in nude mice provides an excellent way to evaluate
      the pathogenesis of tumor growth and metastasis in order to develop therapies, to
      better define the underlying biology of tumor growth and metastasis, and to
      identify new molecular targets. This unit describes an orthotopic model of human
      PDAC in athymic nude mice that closely mimics the human condition. It is
      characterized by diffuse peritoneal, lymphatic, and hepatic metastatic spread and
      manifestations of a cancer cachexic phenotype.

PMID- 21948163
TI  - Orthotopic models of human gastric carcinoma in nude mice: applications for study
      of tumor growth and progression.
AB  - Gastric carcinoma (GC) remains a leading cause of cancer related deaths worldwide
      with the 5-year survival rate in the U.S. at -5% to 15% with existing therapies.
      This tumor is aggressive and has often metastasized to distant sites (liver,
      lung, and adjacent intestine) by the time of diagnosis. Treatment options
      (surgery, radiation, and chemotherapy) are limited and the disease carries a
      grave prognosis for most patients (50% 5-year survival for distal GC; 10% 5-year
      survival for proximal GC). An orthotopic model of human GC in nude mice provides
      an excellent way to evaluate the pathogenesis of tumor growth and metastasis in
      order to develop effective therapies, as well as to better understand the
      underlying biology of gastric tumor growth and metastasis. The protocol described
      in this unit details the development and characterization of an orthotopic model
      of human GC in athymic nude mice with diffuse lymphatic and hepatic metastatic
      spread. This model closely mimics the course of the human disease.

PMID- 21948164
TI  - Metastatic model of colon carcinoma in mice: utility in the study of tumor growth
      and progression.
AB  - Colorectal cancer is the second leading cause of cancer deaths in the United
      States with an estimated 150,000 diagnosed cases and over 56,000 fatalities
      annually (Jemal et al., 2006). Approximately one-third to one-half of cases are
      localized to the colon and rectum and have a favorable prognosis, while one-third
      to one-half present with regional lymph node metastases at diagnosis and
      generally are refractory to various chemotherapeutic regimens. Treatment options
      (surgery, radiation, and chemotherapy) are limited and the disease carries a
      grave prognosis for many patients. An orthotopic model of colon carcinoma in mice
      provides a way to evaluate the pathogenesis of tumor growth and metastasis as an
      aid in developing effective therapies and to better understand the underlying
      biology of colon tumor growth and metastasis. The protocol described in this unit
      details the development and characterization of an orthotopic model of murine
      colon carcinoma in BALB/c mice with diffuse lymphatic and hepatic metastatic
      spread, closely mimicking the course of the human disease.

PMID- 21948165
TI  - Models of melanoma metastasis: using a transient siRNA-based protein inhibition
      strategy in mice to validate the functional relevance of pharmacological agents.
AB  - While a pharmacological agent may inhibit the activity of a protein in cultured
      cells by triggering a particular biological process, it may function differently
      in intact animals. Thus, an assay is needed to rapidly assess whether a drug
      candidate displays the same mechanism of action in vivo as in vitro. The
      experimental approach described in this unit utilizes synthetic siRNA in a
      transient animal assay to define the action of a drug candidate when inhibiting
      the activity of a particular gene. Commercially available synthetic siRNA is
      introduced into cancer cells by nucleofection to reduce protein expression. Cells
      are then introduced into animals and the mechanism responsible for tumor
      inhibition assessed. The action of a compound identified in vitro is then
      compared to that noted in vivo following siRNA-mediated inhibition to determine
      whether it reduces tumor development in the same manner in both systems.

PMID- 21948166
TI  - Application of radiotherapy and chemotherapy protocols to pre-clinical tumor
      models.
AB  - This unit (1) provides background into understanding how agents that target
      specific molecules or receptors (molecular-targeted agents), in particular,
      agents affecting the tumor vasculature (perivasculature network in tumors),
      interact with and modify radiation therapy; (2) details factors affecting
      interpretation of results in murine tumor model experiments utilizing radiation
      therapy and drug combinations; and (3) provides specific protocols for the
      application of radiation therapy, both alone and in combination with chemotherapy
      and/or molecular-targeted agents.

PMID- 21948167
TI  - Preclinical chemotherapeutic tumor models of common childhood cancers: solid
      tumors, acute lymphoblastic leukemia, and disseminated neuroblastoma.
AB  - This unit presents three models used in the Pediatric Preclinical Testing Program
      of the National Cancer Institute (NCI) for preclinical testing of new chemical
      entities (NCEs), along with appropriate methods for data analysis. The first is
      the classical subcutaneous xenograft model used for many solid tumors, the second
      is the disseminated human leukemia model established by Lock and colleagues, and
      the third is a disseminated model of neuroblastoma that recapitulates many of the
      characteristics of advanced clinical disease.

PMID- 21948168
TI  - Agonist-stimulated [35S]GTPgammaS binding.

PMID- 21948170
TI  - Overview of pharmacogenetics.

PMID- 21948169
TI  - Assessing sensitivity to antibacterial topoisomerase II inhibitors.
AB  - Both prokaryotes and eukaryotes have two major classes of topoisomerases that
      make transient single- or double-strand cuts in DNA. While these enzymes play
      critical roles in cellular processes, they are also important targets of
      therapeutic agents. This unit describes assays to use in characterizing
      topoisomerase II-targeting agents in vitro and in bacterial cells. It provides
      protocols for characterizing the action of small molecules against bacterial type
      II topoisomerases in vitro and the in vivo effects of putative topoisomerase II
      targeting antibiotics, as well as for measuring trapped enzyme/DNA covalent
      complexes, the major cytotoxic lesion induced by fluoroquinolones.

PMID- 21948171
TI  - Cytochrome P450 inhibition assays using traditional and fluorescent substrates.
AB  - A key liability in transitioning a new chemical entity (NCE) to a development
      candidate is NCE-related inhibition (or induction) of cytochrome P450 enzymes, a
      superfamily of heme-containing oxygenases that are the major route of first-pass
      metabolism for the majority of marketed drugs. The drawback of a drug/NCE that
      modulates CYP450 enzyme activity occurs when the compound is co-administered with
      another drug that relies on the same P450 enzyme for its metabolism. This could
      result in overdose of the second drug in the case of inhibition, or more rapid
      metabolism of one or both drugs accompanied by loss of efficacy in the case of
      enzyme induction. Screening for the inhibition of CYP450 enzymes is now routine
      in the early stages of evaluating NCEs. This unit describes two inhibition assays
      using traditional and fluorescent substrates.

PMID- 21948172
TI  - Current role of echinocandins in the management of invasive aspergillosis.
AB  - Echinocandins are parenteral antifungals with a unique site of action targeting
      the cell wall synthesis. There are three molecules available, anidulafungin,
      caspofungin, and micafungin, which have fungicidal and fungistatic activity
      against Candida and Aspergillus, respectively, and an excellent safety profile.
      There is consistent proof of clinical activity against Aspergillus for
      caspofungin, while less is known for micafungin and even lees for anidulafungin.
      Micafungin and caspofungin have been successfully used in targeted treatment of
      aspergillosis, prophylaxis, and empirical therapy, both as monotherapy and in
      combination with other antifungals. Caspofungin is approved for empirical therapy
      of febrile neutropenia and salvage treatment of invasive aspergillosis, whereas
      micafungin is only licensed for antifungal prophylaxis in stem cell
      transplantation.

PMID- 21948173
TI  - The 3-state model of muscle regulation revisited: is a fourth state involved?
AB  - The 3-state model of muscle regulation has been useful in explaining the roles of
      Ca2+ and myosin heads in activation and relaxation of striated muscle
      contraction. However, there are some phenomena, which cannot simply be explained
      by the 3-state model. These include increased Ca2+-binding caused by strong
      binding myosin heads and residual active force at low Ca2+ in the case of
      familial hypertrophic cardiomyopathy. Here, I review experimental data which
      provide evidence for an additional state, a myosin-induced Open state present in
      the absence of Ca2+ (Open-Ca2+) which like the normal Open+Ca2+ state, is an
      active state and can allow myosin heads to cycle and generate force. A schematic
      diagram is presented which shows that the formation of the Open-Ca2+ state is on
      a parallel path with the formation of the Open+Ca2+ state and can contribute to
      activation.

PMID- 21948174
TI  - Ex vivo expansion of human Tregs specific for alloantigens presented directly or
      indirectly.
AB  - Adoptive transfer of regulatory T cells (Tregs) prevents GVHD in experimental
      animals. Because antigen activation drives Treg function, we measured the
      frequency, growth requirements, and function of alloantigen-specific
      (allospecific) Tregs from human blood. When alloantigen was presented directly,
      the precursor frequency of allo-specific Tregs in normal individuals was 1.02%
      (95% confidence interval [95% CI]: 0.65-1.59) and non-Tregs 1.56% (95% CI: 0.94
      2.55). When alloantigen was presented indirectly, the frequency of specific Tregs
      was approximately 100-fold less. Purified Tregs were expanded with APCs,
      rapamycin, IL-2, and IL-15. In 12 days, allo-specific Tregs expanded 793-fold
      (95% CI: 480-1107), with duplication approximately every 24 hours. Purified allo
      specific Tregs suppressed responses to specific alloantigen selectively and were
      approximately 100-fold more potent than polyspecific Tregs and nonexpanded Tregs.
      Allo-specific Tregs maintained high expression of Foxp3, Bcl-2, lymphoid homing
      receptor CD62L, and chemokine receptor CCR7, predicting sustained function and
      migration to lymphoid tissues in vivo. Allo-specific Tregs produced TGF-beta and
      IL-10 and expressed more cytoplasmic CTLA-4 compared with non-Tregs. These data
      provide a platform for the selective expansion of Tregs against major and
      possibly minor histocompatibility antigens and predict the feasibility of
      adoptive immunotherapy trials using Tregs with indirect allo-recognition for
      preventing GVHD while sparing GVL effects.

PMID- 21948175
TI  - Mesenchymal stromal cells of myelodysplastic syndrome and acute myeloid leukemia
      patients have distinct genetic abnormalities compared with leukemic blasts.
AB  - Mesenchymal stromal cells (MSCs) are an essential cell type of the hematopoietic
      microenvironment. Concerns have been raised about the possibility that MSCs
      undergo malignant transformation. Several studies, including one from our own
      group, have shown the presence of cytogenetic abnormalities in MSCs from leukemia
      patients. The aim of the present study was to compare genetic aberrations in
      hematopoietic cells (HCs) and MSCs of myelodysplastic syndrome (MDS) and acute
      myeloid leukemia (AML) patients. Cytogenetic aberrations were detected in HCs
      from 25 of 51 AML patients (49%) and 16 of 43 MDS patients (37%). Mutations of
      the FLT3 and NPM1 genes were detected in leukemic blasts in 12 (23%) and 8 (16%)
      AML patients, respectively. Chromosomal aberrations in MSCs were detected in 15
      of 94 MDS/AML patients (16%). No chromosomal abnormalities were identified in
      MSCs of 36 healthy subjects. We demonstrate herein that MSCs have distinct
      genetic abnormalities compared with leukemic blasts. We also analyzed the main
      characteristics of patients with MSCs carrying chromosomal aberrations. In view
      of these data, the genetic alterations in MSCs may constitute a particular
      mechanism of leukemogenesis.

PMID- 21948176
TI  - Essential roles for Pot1b in HSC self-renewal and survival.
AB  - Maintenance of mammalian telomeres requires both the enzyme telomerase and
      shelterin, which protect telomeres from inappropriately activating DNA damage
      response checkpoints. Dyskeratosis congenita is an inherited BM failure syndrome
      disorder because of defects in telomere maintenance. We have previously shown
      that deletion of the shelterin component Pot1b in the setting of telomerase
      haploinsufficiency results in rapid telomere shortening and fatal BM failure in
      mice, eliciting phenotypes that strongly resemble human syskeratosis congenita.
      However, it was unclear why BM failure occurred in the setting of Pot1b deletion.
      In this study, we show that Pot1b plays an essential role in HSC survival.
      Deletion of Pot1b results in increased apoptosis, leading to severe depletion of
      the HSC reserve. BM from Pot1b(Delta/Delta) mice cannot compete with BM from wild
      type mice to provide multilineage reconstitution, indicating that there is an
      intrinsic requirement for Pot1b the maintenance of HSC function in vivo.
      Elimination of the p53-dependent apoptotic function increased HSC survival and
      significantly extended the lifespan of Pot1b-null mice deficient in telomerase
      function. Our results document for the first time the essential role of a
      component of the shelterin complex in the maintenance of HSC and progenitor cell
      survival.

PMID- 21948177
TI  - Adiponectin protects endothelial cells from the damages induced by the
      intermittent high level of glucose.
AB  - Globular adiponectin (gAd) has anti-atherogenic effects on the vascular wall.
      Intermittent hyperglycemia induces endothelial cells (ECs) injury but the
      physiological factors that may protect against ECs damage are largely unknown. In
      the present study, we investigated the effect of gAd on ECs dysfunction induced
      by intermittent high glucose. The gAd significantly attenuated intermittent high
      glucose-induced apoptosis and oxidative stress in human umbilical vein
      endothelial cells. This was achieved by decreasing caspase-3 and 3-nitrotyrosine
      protein expression, increasing nitric oxide (NO) secretion and phosphorylation of
      Akt, AMPK, and endothelial nitric oxide synthase protein expression. Pretreatment
      with a phosphatidylinositol 3' kinase (PI3K) inhibitor, LY294002, partly reversed
      adiponectin's anti-apoptotic effect. Taken together, our results indicate that
      gAd acts as a critical physiological factor which protects against fluctuating
      high glucose-induced endothelial damage. It may act via attenuating apoptosis and
      increasing synthesis of NO through both the PI3K/AKT and AMPK signaling pathway
      to reduce oxidative stress and cell apoptosis.

PMID- 21948178
TI  - A hypertriglyceridemic state increases high sensitivity C-reactive protein of
      Japanese men with normal glucose tolerance.
AB  - Both fasting and postprandial hypertriglyceridemia have been identified as risk
      markers for cardiovascular disease. High-sensitivity C-reactive protein (hs-CRP),
      known to independently predict future cardiovascular disease, has also been
      reported to be a direct participant in the progression of atherosclerosis. We
      evaluated whether or not fasting and/or postprandial hypertriglyceridemia
      influence hs-CRP of men with normal glucose tolerance. According to the
      triglyceride (TG) level, measured before and 1 and 2 h after a meal tolerance
      test, subjects were classified into a normotriglyceridemic (NTG) group (n = 86),
      a postprandial hypertriglyceridemia (PHTG) group (n = 50), or a fasting
      hypertriglyceridemia (FHTG) group (n = 53). Hs-CRP and HOMA-R were significantly
      higher in the FHTG group than in the other groups (P < 0.01). The PHTG group had
      higher hs-CRP than the NTG group (P < 0.05). No significant differences in age,
      BMI, LDL cholesterol, or carotid intima-media thickness were found in comparison
      of the three groups. Multivariate linear regression analysis showed that the area
      under the TG curve (AUC-TG), HbA1c, and BMI were independently correlated with hs
      CRP (P < 0.001, P = 0.016, P = 0.032, respectively). Our data suggests that a
      hypertriglyceridemic state is associated with hs-CRP irrespective of BMI, LDL-C,
      and HDL-C, indicating that hs-CRP might represent chronic inflammation induced by
      hypertriglyceridemia in Japanese men with normal glucose tolerance.

PMID- 21948179
TI  - Dual-phase computed tomography for assessment of pancreatic fibrosis and
      anastomotic failure risk following pancreatoduodenectomy.
AB  - INTRODUCTION: Delayed or decreased computed tomography (CT) enhancement
      characteristics in pancreatic fibrosis have been described. METHODS: A review of
      157 consecutive patients with preoperative dual-phase CT between 2004 and 2009
      was performed. Pancreatic CT attenuation upstream from the tumor was measured in
      the pancreatic and hepatic imaging phases. The ratio of the mean CT attenuation
      value [hepatic to pancreatic phase; late/early (L/E) ratio] and histological
      grade of pancreatic fibrosis was correlated with the development of a clinically
      relevant pancreatic anastomotic failure (PAF) and other clinical parameters.
      RESULTS: A clinically relevant PAF was observed in 21 patients (13.4%) with
      morbidity and mortality of 39.5% and 0%, respectively. The PAF group showed
      maximum enhancement in the pancreatic and washout in the hepatic CT phase, while
      the no PAF group showed a delayed enhancement pattern. Degree of pancreatic
      fibrosis and L/E ratio were significantly lower for the PAF group than the no PAF
      group (0.86 +/- 0.14 vs. 1.09 +/- 0.24; P < 0.0001 and 21.0 +/- 17.9 vs. 40.4 +/-
      29.8; P < 0.0001); fewer PAF patients showed an atrophic histological pattern
      (14% vs. 39%; P = 0.046). The L/E ratio was positively correlated with pancreatic
      fibrosis. Pancreatic fibrosis and L/E ratio increased with larger duct size (P <
      0.001), the presence of diabetes (P < 0.05), and the surgeon's assessment of
      pancreas firmness (P < 0.001). In multivariate analyses, L/E ratio and body mass
      index were significant predictors for the development of a clinically relevant
      PAF; a 0.1-U increase of L/E ratio decreased the odds of a PAF by 54%.
      CONCLUSION: Pancreatic CT enhancement pattern can accurately assess pancreatic
      fibrosis and is a powerful tool to predict the risk of developing a clinically
      relevant PAF following PD.

PMID- 21948180
TI  - Robotic single-port cholecystectomy using a new platform: initial clinical
      experience.
AB  - BACKGROUND: The technique of single-port laparoscopy was developed over the past
      years in an attempt to reduce the invasiveness of surgery. A reduction of
      incisions and their overall size might result in enhanced postoperative cosmesis
      and potentially reduce pain when compared to conventional techniques. While
      manual single-port laparoscopy is technically challenging, a newly approved
      robotic platform used with the da Vinci Si System (Intuitive Surgical, Sunnyvale,
      CA, USA) might overcome some of the difficulties of this technique. METHODS:
      Patients with cholelithiasis were scheduled for robotic single-port
      cholecystectomy in an initial clinical trial. Demographic data, intra- and short
      term postoperative results were assessed prospectively. RESULTS: Twenty-eight
      patients (22 females/6 males; median age, 48 years) underwent robotic single-port
      cholecystectomy in our first week of clinical cases. Median OR time was 80 min
      with a median docking time of 8 min and median robotic console time of 53 min.
      Two patients underwent intraoperative cholangiography. Eight cases presented with
      adhesions, tissue alterations, or anatomical abnormalities. No conversions, intra
      or postoperative complications occurred. CONCLUSION: Robotic single-port
      cholecystectomy appears feasible and safe in our early experience. The robotic
      approach to single-port surgery seems to overcome some of the technical
      difficulties of manual single-port surgery. This robotic platform may facilitate
      completion of more complex cases.

PMID- 21948181
TI  - Segmental internal sphincterotomy--a new technique for treatment of chronic anal
      fissure.
AB  - OBJECTIVE: Lateral internal sphincterotomy is an effective treatment for fissure
      in ano but carries a definite risk of incontinence. In trial to avoid this
      complication, segmental lateral internal sphincterotomy was used to treat chronic
      anal fissures. DESIGN: The lateral internal sphincterotomy was done in two parts
      and at different planes. SETTING: This study was conducted in the General Surgery
      Department, Zagazig University Hospital, Egypt. PATIENTS: This study was
      undertaken on 50 patients (43 men and seven women, with mean age of 37.3 years)
      with chronic fissure in ano from January 2009 to December 2010. INTERVENTIONS:
      Under general or local anesthesia, lateral internal sphincterotomy was done in
      two segments under direct vision. Preoperative and postoperative anal manometry
      study was recorded. MAIN OUTCOME MEASURES: Postoperative course with early and
      long-term results were recorded. Mean follow-up was 18.5 months (ranging from 6
      to 24 months). RESULTS: In 31 patients, the technique was done under general
      anesthesia and the remainder under local anesthesia. The fissures and anal wounds
      were healed within 4 weeks. Pain was significantly reduced in all patients at day
      1 postoperative. Early complications included mild hematoma and urine retention
      in one male patient (2%). No transient or any persistent degree of incontinence
      occurred in these patients group. CONCLUSION: Segmental lateral internal
      sphincterotomy is a safe, easy, and effective procedure and not associated with
      risk of incontinence for the treatment of chronic anal fissure.

PMID- 21948182
TI  - Intra-abdominal pressure and abdominal perfusion pressure early in severe acute
      pancreatitis misses the forest for the trees.

PMID- 21948183
TI  - Can blended classroom and distributed learning approaches be used to teach
      medical students how to initiate behavior change counseling during a clinical
      clerkship?
AB  - Medical school curricula often provide insufficient time and instruction for
      health behavior change counseling. We examined the feasibility of blending
      classroom and distributed learning experiences to teach medical students how to
      initiate health behavior change counseling and analyzed the impact of this
      approach on their attitudes, knowledge, and skills. Usage patterns and pre- to
      post-class attitude and knowledge changes were assessed with self-report
      questions among 153 third year family medicine clerkship students. Most students
      viewed at least 90% of the online written content and took an average of 41 min
      (SD = 24 min 35 s) to view all of the content. Students' confidence in their
      ability to help patients change unhealthy behaviors significantly improved (p <
      .01). The blended learning curriculum facilitated learning of behavior change
      skills, encouraged interaction with course materials, and improved medical
      students' self confidence for using health behavior change skills.

PMID- 21948184
TI  - The dominant human conjunctival epithelial CD8alphabeta+ T cell population is
      maintained with age but the number of CD4+ T cells increases.
AB  - The conjunctiva is a highly specialized ocular mucosal surface that, like other
      mucosa, houses a number of leukocyte populations. These leukocytes have been
      implicated in age-related inflammatory diseases such as dry-eye, but their
      phenotypic characteristics remain largely undetermined. Existing literature
      provides rudimentary data from predominantly immunohistochemical analyses of
      tissue sections, prohibiting detailed and longitudinal examination of these cells
      in health and disease. Using recovered cells from ocular surface impression
      cytology and flow cytometry, we examined the frequency of leukocyte subsets in
      human conjunctival epithelium and how this alters with age. Of the total CD45+
      leukocyte population within the conjunctival epithelium, 87% [32-99] (median)
      [range] comprised lymphocytes, with 69% [47-90] identified as CD3 + CD56- T
      cells. In contrast to peripheral blood, the dominant conjunctival epithelial
      population was TCRalphabeta + CD8alphabeta + (80% [37-100]) with only 10% [0-56%]
      CD4+ cells. Whilst a significant increase in the CD4+ population was seen with
      age (r = 0.5; p < 0.01) the CD8+ population remained unchanged, resulting in an
      increase in the CD4:CD8 ratio (r = 0.5;p < 0.01). IFNgamma expression was
      detectable in 18% [14-48] of conjunctival CD4+ T cells and this was significantly
      higher among older individuals (<35 years, 7[4-39] vs. >65 years, 43[20-145]; p <
      0.05). The elevation of CD4+ cells highlights a potentially important age-related
      alteration in the conjunctival intra-epithelial leukocyte population, which may
      account for the vulnerability of the aging ocular surface to disease.

PMID- 21948185
TI  - The influence of short-term L-arginine supplementation on rats' muscular and
      hepatic cells in ischemia-reperfusion syndrome.
AB  - Due to the complex mechanisms of L-arginine activity, it is difficult to
      determine the clinical significance of supplementation with this amino acid. The
      objective of this study was to determine the influence of short-term
      supplementation with L-arginine in stress conditions, induced by ischemia
      reperfusion syndrome, by assessing the damage to muscular and hepatic cells on
      the basis of creatine kinase (CK), alanine aminotransferase (ALAT) and aspartic
      aminotransferase (AspAT) activity in blood and the level of oxygen free radicals
      in analyzed tissues of rats. We observed that induced ischemia of hind limb
      caused an increase in CK, ALAT and AspAT activity and an increase in the level of
      free radicals in liver, but not in skeletal muscle. Supplementation with L
      arginine led to a reduction in serum activity of CK and AspAT and reduction of
      the level of free radicals in analysed tissues. Simultaneous supplementation with
      L -arginine AND L-NAME resulted in a reversal of changes induced by L-arginine
      supplementation in the case of AspAT and free radicals in skeletal muscle. The
      results indicate that under conditions of ischemia-reperfusion, short-term
      administration of L-arginine has a protective effect on skeletal muscle
      manifesting itself by reduction of CK in the serum and reduction of free radicals
      level in THIS tissue.

PMID- 21948186
TI  - Lipid peroxidation, antioxidant activities and stress protein (HSP72/73, GRP94)
      expression in kidney and liver of rats under lithium treatment.
AB  - The present work was aimed at studying the effects of a subchronic lithium
      treatment on rat liver and kidneys, paying attention to the relationship between
      lithium toxicity, oxidative stress, and stress protein expression. Male rats were
      submitted to lithium treatment by adding 2 g of lithium carbonate/kg of food for
      different durations up to 1 month. This treatment led to serum concentrations
      ranging from 0.5 mM (day 7) to 1.34 mM (day 28) and renal insufficiency
      highlighted by an increase of blood creatinine and urea levels and a decrease of
      urea excretion. Lithium treatment was found to trigger an oxidative stress both
      in kidney and liver, leading to an increase of lipid peroxidation level (TBARS)
      and of superoxide dismutase and catalase activities. Conversely, glutathione
      peroxidase activity was reduced. Constitutive HSP73 (heat shock protein 73)
      expression was not modified by lithium treatment, whereas inducible HSP72 was
      down-regulated in kidney. GRP94 (glucose regulated protein 94) appeared as two
      isoforms of 92 and 98 kDa: the 98-kDa protein being overexpressed in kidney by
      lithium treatment whereas 92-kDa protein was underexpressed both in kidney and
      liver.

PMID- 21948187
TI  - Case-matched series of enhanced versus standard recovery pathway in minimally
      invasive colorectal surgery.
AB  - BACKGROUND: Accelerated recovery pathways may reduce length of hospital stay
      after surgery but there are few data on minimally invasive colorectal operations.
      METHODS: An enhanced recovery pathway (ERP) was instituted, including
      preoperative analgesia, limited intravenous fluids and opiates, and early
      feeding. Intrathecal analgesia was administered as needed, but epidural analgesia
      was not used. The first 66 patients subjected to the ERP were case-matched by
      surgeon, procedure and age (within 5 years) with patients treated previously in a
      fast-track pathway (FTP). Short-term and postoperative outcomes to 30 days were
      compared. RESULTS: Hospital stay was shorter with the ERP than the FTP: median
      (interquartile range, i.q.r.) 3 (2-3) versus 3 (3-5) days (P < 0.001). A 2-day
      hospital stay was achieved in 44 and 8 per cent of patients respectively (P <
      0.001). Patients in the ERP had a shorter time to recovery of bowel function:
      median (i.q.r.) 1 (1-2) versus 2 (2-3) days (P < 0.001). Thirty-day complication
      rates were similar (32 per cent ERP, 27 per cent FTP; P = 0.570). Readmissions
      within 30 days were more common with ERP, but the difference was not
      statistically significant (10 versus 5 patients; P = 0.170). Total hospital stay
      for those readmitted was shorter in the ERP group (18 versus 23 days).
      CONCLUSION: ERP decreased the length of hospital stay after minimally invasive
      colorectal surgery.

PMID- 21948188
TI  - Towards an integrated understanding of the structural characteristics of protein
      residue networks.
AB  - A protein residue network or PRN is a network induced by spatial contacts between
      amino acid residues of a protein. Studies of the structure of PRNs have revealed
      a list of network characteristics common to a diverse class of proteins.
      Explanations for the observed network characteristics for protein folding have
      been suggested but not tested in an integrated way. In this article, in silico
      experiments are performed to understand how structural characteristics of PRNs
      influence protein folding as modeled by a search problem. We find that the blend
      of structural characteristics PRNs possess help to place them in a sweet spot
      within the space of all network configurations tested. PRNs are plausible 3D
      structures and yield competitive search performances. Hence, it appears that PRNs
      are in a form suited to the function they evolved into. However, this conclusion
      is partially contingent upon the fitness function preferentially satisfying short
      range links but also allowing short- and long-range interactions to cooperate
      towards the satisfaction of all links. We close with a discussion on the rather
      intricate interplay among the three main structural characteristics of PRNs,
      i.e., clustering, average path length, and assortativity, and their impact on
      search performance and 3D structure plausibility.

PMID- 21948189
TI  - Assessing responses to treatment of opportunistic mycoses and salvage strategies.
AB  - Invasive fungal disease (IFD) in immunocompromised patients remains a major cause
      of morbidity and mortality and there is a pressing need for studies of novel
      antifungal agents and strategies to improve outcomes. Trial design details often
      determine not only the appropriate interpretation of the results, but also their
      translation into clinical practice. However, the conduct of IFD clinical trials
      remains challenging due to the rarity of IFD, heterogeneity of underlying
      diseases, and the lack of clear and standardized response criteria. Response
      assessments are influenced by host, underlying disease and treatment factors as
      well as eligibility criteria. In addition, the criteria used to assess response,
      when response is assessed and the type of antifungal therapy under study can
      impact response evaluations. This article will discuss recent trials of primary,
      salvage, empiric, and prophylactic antifungal therapy with specific attention to
      the design of these antifungal therapy trials and how their designs influence
      their interpretation. The potential role of surrogate markers, such as the
      galactomannan index, fungal deoxyribonucleic acid polymerase chain reaction
      assay, and (18F) fluorodeoxyglucose positron emission tomography scans in
      establishing the early diagnosis of IFD, as well as enhancing the ability to
      assess outcomes to antifungal therapy, and thereby the optimal duration of
      antifungal therapy, will be discussed.

PMID- 21948191
TI  - Transcriptional control of T-cell development.
AB  - T lymphocytes, which are central players in orchestrating immune responses,
      consist of several subtypes with distinct functions. The thymus is an organ where
      hematopoietic progenitors undergo sequential developmental processes to give rise
      to this variety of T-cell subsets with diverse antigen specificity. In the
      periphery, naive T cells further differentiate into effector cells upon
      encountering antigens. There are several developmental checkpoints during T-cell
      development, where regulation by a combination of transcription factors imprints
      specific functional properties on precursors. The transcription factors E2A, GATA
      binding protein 3 (Gata3) and RUNT-related transcription factor (Runx) are
      involved at various stages in the differentiation of double-negative thymocytes
      and in beta-selection, as are transcription factors from the Notch signaling
      pathway; other transcription factors such as B-cell lymphoma/leukemia 11b
      (Bcl11b), myeloblastosis viral oncogene homolog (Myb) and inhibitor of DNA
      binding 3 (Id3) are involved at specific stages. Differentiation of T cells into
      helper versus cytotoxic cells involves not only antagonistic interplay between
      Runx and T(h) inducing POZ-Kruppel factor (ThPOK) but also complex interactions
      between MAZR, Gata3 and Myb in the activation and silencing of genes such as Cd4
      and Cd8 as well as the gene that encodes ThPOK itself. A wide range of well
      defined transcription factors, including signal transducer and activator of
      transcriptions (STATs), T-bet, Gata3, nuclear factor of activated T cell (NFAT),
      adaptor-related protein complex 1 (AP-1) and nuclear factor kappaB (NF-kappaB),
      are known to shape T(h)1/T(h)2 differentiation. Runx and Gata3 also operate in
      this process, as do c-Maf and recombining binding protein for immunoglobulin
      Jkappa region (RBP-J) and the chromatin-reorganizing protein special AT-rich
      sequence-binding protein 1 (SATB1). In this review, we briefly discuss how T-cell
      characteristics are acquired and become divergent from the point of view of
      transcriptional regulation.

PMID- 21948190
TI  - Cross-bridge apparent rate constants of human gallbladder smooth muscle.
AB  - This paper studies human gallbladder (GB) smooth muscle contractions. A two-state
      cross-bridge model was used to estimate the apparent attachment and detachment
      rate constants, as well as increased Ca2+ concentration from the peak active
      stress during the isometric contraction. The active stress was computed from a
      mechanical model based entirely on non-invasive routine ultrasound scans. In the
      two-state cross-bridge model, the two apparent rate constants, representing the
      total attached/detached cross-bridges, respectively, were estimated using active
      stress prediction for 51 subjects undergoing cholecystokinin-provocation test,
      together with estimates from the four-state cross-bridge model for a swine
      carotid, bovine tracheal and guinea pig GB smooth muscles. The study suggests
      that the apparent rate constants should be patient-specific, i.e. patients with a
      lower stress level are characterized by smaller apparent rate constants. In other
      words, the diseased GB may need to develop fast cycling cross-bridges to
      compensate in the emptying process. This is a first step towards more
      quantitative and non-invasive measures of GB pain, and may provide useful insight
      in understanding GB motility and developing effective drug treatments.

PMID- 21948192
TI  - Endothelial dysfunction in rat mesenteric artery after regional cardiac ischaemia
      reperfusion.
AB  - In most previous studies, ischaemia-reperfusion (I/R)-induced vascular injury
      referred to injury in the tissue or blood vessel that was directly subjected to
      I/R. However, less attention has been focused on remote vascular injury that
      might be caused by cardiac I/R. In the present study, we aimed to assess whether
      cardiac I/R could affect vasoconstriction and vasodilatation in mesenteric
      arteries from Sprague-Dawley rats. Left anterior descending coronary arteries
      from adult male Sprague-Dawley rats were occluded (60 min) and then reperfused
      (120 min). Changes in haemodynamic parameters indicated that this procedure
      caused evident cardiac dysfunction. In mesenteric arteries isolated from the
      animals, cardiac I/R significantly increased the maximal contractions in response
      to KCl, 5-hydroxytryptamine, phenylephrine and U46619 and decreased the maximal
      relaxation in response to acetylcholine, but not to sodium nitroprusside,
      compared with sham-operated animals. The nitric oxide synthase inhibitor L-NAME
      abolished differences of contractile responses to phenylephrine between sham
      operated and I/R rats. The antioxidant N-acetyl-L-cysteine reversed the
      impairment of acetylcholine-stimulated vasodilatation induced by regional cardiac
      I/R. However, L-NAME caused a similar degree of inhibition of acetylcholine
      stimulated relaxation in mesenteric arteries from sham-operated and I/R rats.
      Electron microscopy revealed that mesenteric arterial endothelial structure was
      degraded in the I/R group and that N-acetyl-L-cysteine treatment prevented this
      structural damage. In conclusion, regional cardiac I/R caused by transient
      occlusion and reperfusion of the left anterior descending coronary artery results
      in peripheral vascular endothelial dysfunction.

PMID- 21948193
TI  - Centenary of the Anglo-American high-altitude expedition to Pikes Peak.
AB  - This year (2011) marks the centenary of one of the most important early research
      expeditions to high altitude. The principal participants were J. S. Haldane and
      C. G. Douglas from Oxford, Y. Henderson from Yale and E. C. Schneider from
      Colorado College. Pikes Peak just outside Colorado Springs proved to be an
      excellent venue because of its substantial altitude of 4300 m, convenient access
      via a cog railway and comfortable living accommodation. The expedition had a
      classical design, with measurements made first at sea level, then on the summit
      for 5 weeks and then at sea level again. The extensive scientific programme
      included descriptions of acute mountain sickness, many measurements of partial
      pressures in alveolar gas and arterial blood, changes in ventilation, including
      periodic breathing, exercise measurements and a large number of blood studies.
      One error was the conclusion that the arterial P(O(2)) could considerably exceed
      the alveolar value, implying oxygen secretion by the lung, but this should not
      detract from the other important advances. Mabel FitzGerald was invited to be a
      member of the expedition but did not join the men on the summit. Instead, she
      visited various mining camps in Colorado at somewhat lower altitudes and carried
      out classical studies of alveolar gas partial pressures and haemoglobin values.
      Indeed, her results of alveolar P(O(2)) and P(CO(2)) are frequently cited today.
      The Pikes Peak expedition was a model and it had an extensive influence on later
      studies.

PMID- 21948194
TI  - Computational analyses of CO-rebreathing methods for estimating haemoglobin mass
      in humans.
AB  - Measurement of haemoglobin mass (M(Hb)) is used to quantify alterations in oxygen
      delivery during exercise training or acclimatization to altitude. Uptake of
      carbon monoxide by haemoglobin is the basis of the common non-radioactive methods
      to determine M(Hb) in humans. This study used a validated mathematical model to
      simulate CO uptake during rebreathing protocols and to determine sources of
      errors in estimation of M(Hb). Our previously published model was validated using
      experimentally measured carboxyhaemoglobin levels (%HbCO) from arterial,
      capillary and venous blood sites of human subjects during CO-rebreathing
      protocols. This model was then used to simulate various CO-rebreathing protocols
      in 24 human subjects with known M(Hb). Using variables generated by the model,
      M(Hb) was estimated on the basis of assumptions typically made for calculating
      the volume of CO bound to myoglobin, the volume of CO exhaled and the volume of
      CO in the rebreathing system. It was found that inaccurate estimation of the
      volume of CO bound to myoglobin was the major source of error in determination of
      M(Hb). Additionally, the size of the error was found to depend on the site of
      blood sampling because of differences in %HbCO. Regression equations were
      developed to improve the estimation of volume of CO bound to myoglobin, and a new
      protocol that is less dependent on the site of blood sampling is proposed.

PMID- 21948195
TI  - Endogenous surface expression of DeltaF508-CFTR mediates cAMP-stimulated Cl(-)
      current in CFTR(DeltaF508/DeltaF508) pig thyroid epithelial cells.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is both an anion
      channel and a regulator of other transport proteins. Mutations in the CFTR gene
      underlie the human disease, cystic fibrosis. The most common CFTR mutation,
      DeltaF508, produces a misfolded protein which traffics improperly. The
      availability of transgenic CFTR(DeltaF508/DeltaF508) pigs allows measurement of
      the impact of DeltaF508 in native tissue. Thyroid epithelia respond to cAMP
      elevating agents by increasing anion transport, a process reliant on functional
      CFTR. To assess whether endogenous levels of DeltaF508-CFTR mediate thyroid
      transport, primary thyroid epithelial cultures (pThECs) were grown from newborn
      CFTR(+/+) (wild-type) and CFTR(DeltaF508/DeltaF508) (DeltaF) pig thyroids and the
      stimulated, secretory components of short-circuit current (I(sc)) compared.
      Surface biotinylation studies assessed the surface presentation of DeltaF508
      CFTR. Baseline I(sc) levels of both wild-type and DeltaF pThECs consisted of an
      amiloride-sensitive component. In DeltaF pThECs, this mirrored previous
      measurements in CFTR(-/-) (knockout) pThECs. Surprisingly, elevation of cAMP
      transiently increased I(sc) to peak levels ~65% of those achieved by wild-type.
      In contrast, knockout pThECs were indifferent to cAMP activation. In DeltaF
      pThECs, total DeltaF508-CFTR expression was ~9% that of wild-type, consistent
      with misfolding and enhanced degradation. Surface biotinylation studies indicated
      that ~4% of the total DeltaF508 resided at the surface and did not increase with
      cAMP elevation. The present findings show that low endogenous levels of pig
      DeltaF508-CFTR can mediate substantial anion transport by thyroid epithelia.
      These data suggest that both wild-type and DeltaF508-CFTR regulate additional
      thyroid transporters, and together co-ordinate the overall I(sc) response.

PMID- 21948196
TI  - Global conformations of proteins as predicted from the modeling of their CZE
      mobility data.
AB  - Estimations of protein global conformations in well-specified physicochemical
      microenvironments are obtained through global structural parameters defined from
      polypeptide-scale analyses. For this purpose protein electrophoretic mobility
      data must be interpreted through a physicochemical CZE model to obtain estimates
      of protein equivalent hydrodynamic radius, effective and total charge numbers,
      hydration, actual ionizing pK and pH-near molecule. The electrical permittivity
      of protein domain is also required. In this framework, the solvent drag on
      proteins is obtained via the characteristic friction power coefficient associated
      with the number of amino acid residues defining the global chain conformation in
      solution. Also, the packing dimension related to the spatial distribution of
      amino acid residues within the protein domain is evaluated and discussed. These
      scaling coefficients together with the effective and total charge number
      fractions of proteins provide relevant interpretations of protein global
      conformations mainly from collapsed globule to hybrid chain regimes. Also,
      protein transport properties may be estimated within this framework. In this
      regard, the central role played by the friction power coefficient in the
      evaluation of these properties is highlighted.

PMID- 21948197
TI  - A multicentre community-based study of dementia cases and subcases in older
      people in China--the GMS-AGECAT prevalence and socio-economic correlates.
AB  - BACKGROUND: Previous studies indicated overall relatively low prevalence of
      dementia in older people in China, which may be biased by studied samples or
      methods. We determined the prevalence of dementia cases and subcases in China and
      examined their socio-economic correlates. METHODS: Using the Geriatric Mental
      State interview, we examined random samples of 2917 participants aged >= 65 years
      in urban and rural Anhui, China in 2001-2003, and 3327 in four other provinces in
      2008-2009. Dementia cases and subcases were diagnosed by Geriatric Mental State
      Automated Geriatric Examination for Computer Assisted Taxonomy. RESULTS: Age
      standardised prevalence for cases and subcases of dementia in the Anhui elders
      was 7.20% (95%CI 6.29%-8.20%) and 10.5% (9.38%-11.6%), and in the four provinces,
      9.86% (8.80%-10.9%) and 8.51% (7.51%-9.52%). The matched figures among the
      participants who were literate were 3.05% (2.08%-4.02%) and 10.0% (8.38%-11.6%),
      and 4.92% (3.89%-5.96%) and 6.76% (5.55%-7.96%), respectively. There were higher
      prevalence rates of dementia cases and subcases in the rural elders than in the
      urban. Both the Anhui and four-province studies showed an obvious association of
      dementia with higher and lower incomes among elders who had lower educational
      levels or had the lowest occupational class. The highest risk of dementia was
      found in those who were illiterate but had the highest income or had the job of
      business/nonmanual labouring. CONCLUSIONS: People in China have a higher
      prevalence of dementia than previously reported. Its U-shaped relationship with
      income and the excess subcases prevalence predicates a significant burden of
      disease, both now and for the future, suggesting preventive strategy for dementia
      in China.

PMID- 21948198
TI  - Is the accuracy of prior preterm birth history biased by delivery
      characteristics?
AB  - To assess the sensitivity of birth certificates to preterm birth history and
      determine whether omissions are randomly or systemically biased. Subjects who
      experienced a preterm birth followed by a subsequent pregnancy were identified in
      a regional database. The variable "previous preterm birth" was abstracted from
      birth certificates of the subsequent pregnancy. Clinical characteristics were
      compared between subjects who were correctly versus incorrectly coded. 713
      subjects were identified, of whom 65.5% were correctly coded in their subsequent
      pregnancy. Compared to correctly coded patients, patients who were not correctly
      identified tended to have late and non-recurrent preterm births or deliveries
      that were secondary to maternal or fetal indications. A recurrence of preterm
      birth in the subsequent pregnancy was also associated with correct coding. The
      overall sensitivity of birth certificates to preterm birth history is suboptimal.
      Omissions are not random, and are associated with obstetrical characteristics
      from both the current and prior deliveries. As a consequence, resulting
      associations may be flawed.

PMID- 21948199
TI  - The association of child mental health conditions and parent mental health status
      among U.S. Children, 2007.
AB  - The purpose of this study is to examine the association of child mental health
      conditions and parent mental health status. This study used data from the 2007
      National Survey of Children's Health on 80,982 children ages 2-17. The presence
      of a child mental health condition was defined as a parent-reported diagnosis of
      at least one of seven child mental health conditions. Parent mental health was
      assessed via a 5-point scale. Logistic regression was used to assess the
      association of child mental health conditions and parent mental health status,
      while examining socioeconomic, parent, family, and community factors as potential
      effect modifiers and confounders of the association. 11.1% of children had a
      mental health condition (95% CI = 10.5-11.6). The prevalence of child mental
      health conditions increased as parent mental health status worsened.
      Race/ethnicity was the only significant effect modifier of the child-parent
      mental health association. After adjustment for confounders, the stratum-specific
      adjusted odds ratios (95% CI) of child mental health conditions related to a one
      level decline in parent mental health were: 1.44 (1.35-1.55) for non-Hispanic
      whites, 1.24 (1.06-1.46) for non-Hispanic blacks, 1.04 (0.81-1.32) for Hispanics
      from non-immigrant families, 1.21 (0.96-1.93) for Hispanics from immigrant
      families, and 1.43 (1.21-1.70) for non-Hispanic other race children. The effect
      of parent mental health status on child mental health conditions was significant
      only among non-Hispanic children. Parent-focused interventions to prevent or
      improve child mental health conditions may be best targeted to the sub
      populations for whom parent and child mental health are most strongly associated.

PMID- 21948200
TI  - Comparing the burden: what can we learn by comparing regulatory frameworks in
      abortion and fertility services?
AB  - In the UK, regulation of clinical services is being restructured. We consider two
      clinical procedures, abortion and IVF treatment, which have similar ethical and
      political sensitivities. We consider factors including the law, licensing,
      inspection, amount of paperwork and reporting requirements, the reception by
      practitioners and costs, to establish which field has the greater 'regulatory
      burden'. We test them based on scientific, ethical, social, political factors
      that might explain differences. We find that regulatory burden borne by IVF
      services is greater than in abortion, but none of the explanatory theses can
      provide a justification of this phenomenon. We offer an alternative explanation
      based on regulatory 'overspill' from research regulation and policy making,
      conceptualisation of risk regulation and a high public profile that locks a
      regulator into self-preservation. 

PMID- 21948201
TI  - Genetic relatedness and chemical profiles in an unusually peaceful eusocial bee.
AB  - Colonies of the stingless bee Tetragonilla collina frequently occur in unusually
      high densities and in direct neighborhood (nest aggregations), in rainforests of
      Southeast Asia. To investigate whether close relatedness and/or similar chemical
      profiles facilitate the co-occurrence of multiple T. collina colonies, we
      investigated aggressive behavior, genetic relatedness and cuticular hydrocarbon
      (CHC) profiles within and between colonies and nest aggregations. Although 17 out
      of 19 colonies within aggregations were largely unrelated, intraspecific
      aggression between different colonies was basically absent both within and among
      aggregations. This lack of aggression should favor social parasitism and hence
      the occurrence of unrelated individuals within a colony. However, low within
      colony relatedness was found in only five out of 19 colonies where it may be
      explained by queen turnover or the occurrence of foreign workers. CHC profiles of
      colonies within and among aggregations were statistically different. However,
      many workers could chemically not be assigned to their maternal colony,
      indicating considerable overlap among colonies in odor profiles of workers.
      Moreover, odor profiles tended to be more similar within than among aggregations,
      although most colonies were unrelated. Thus, CHC profiles were a poor indicator
      of relatedness in T. collina. The lack of correlation between relatedness and
      chemical similarity in T. collina may be explained by the incorporation of resin
      derived terpenes in their CHC profiles. The composition of these terpenes was
      highly similar among colonies, particularly within aggregations, hence
      potentially decreasing chemical distinctiveness and increasing behavioral
      tolerance.

PMID- 21948202
TI  - Hairpencil volatiles influence interspecific courtship and mating between two
      related moth species.
AB  - Reproductive isolation between sympatric, closely related species can be
      accomplished through a variety of pre-zygotic isolating mechanisms, including
      courtship-signaling behavior that involves pheromones. In the moths Heliothis
      virescens and H. subflexa, males display abdominal hairpencils (HP), which
      release volatile chemicals during courtship. In this study, we demonstrated that
      HP volatiles released by male H. subflexa function to improve mating success with
      conspecific females. Interspecific mating experiments were conducted to determine
      any influence of HP volatiles on species isolation. Female H. virescens and H.
      subflexa were observed during courtship with males of the other species,
      following either sham-operation or ablation of HPs, both with and without
      concurrent presentation of HP volatiles. Mating success was improved by co
      presentation of HP extract from males of the same species during courtship.
      Ablation of HPs improved mating between H. subflexa females and H. virescens
      males. During interspecific matings, male H. virescens attempted copulation less
      frequently in the presence of H. virescens HP extract, though H. subflexa males
      were not affected by the presence of H. subflexa HP extract. This suggests that
      HP volatiles produced by males of each species may inhibit mating between species
      through effects on males (H. virescens) and females (H. subflexa).

PMID- 21948203
TI  - Unintended consequences of a standard admission order set on venous
      thromboembolism prophylaxis and patient outcomes.
AB  - BACKGROUND: Standard order sets often increase the use of desirable interventions
      for patients likely to benefit from them. Whether such order sets also increase
      misuse of these interventions in patients potentially harmed by them is unknown.
      We measured the association between a paper-based standard admission order set
      with a venous thromboembolism pharmacoprophylaxis (VTEP) module and use of VTEP
      for patients likely to benefit from it as well as patients with unclear benefit
      or potential harm from it. METHODS: We conducted a retrospective cohort study
      using administrative and pharmacy charge data of patients admitted between 1 July
      2005 and 31 December 2008 to two medical and three surgical services that
      implemented a standard admission order set in August 2006. The primary outcome
      was use of VTEP in patients with likely benefit, unclear benefit, and potential
      harm from VTEP prior to and following order set implementation. KEY RESULTS: A
      total of 8,429 patients (32%) were admitted prior to and 17,635 (68%) following
      order set implementation. There was a small unadjusted rise in overall VTEP use
      after implementation (51% to 58%, p < 0.001). In multivariable models with
      interrupted time series analysis, patients with potential harm from VTEP had the
      largest increase in VTEP use at the time of implementation [adjusted odds ratio =
      1.58; 95% confidence interval (CI), 1.12-2.22]. The increased likelihood of
      receiving VTEP in this subgroup gradually returned to baseline (adjusted odds
      ratio per month = 0.98; 95% CI, 0.96-0.99). CONCLUSIONS: Implementation of a
      standard admission order set transiently increased VTEP in patients with
      potential harm from it. Order set and guideline success should be judged based on
      the degree to which they successfully target patients likely to benefit from the
      intervention without inadvertently targeting patients potentially harmed.

PMID- 21948204
TI  - Governance around quality of care at hospitals that disproportionately care for
      black patients.
AB  - BACKGROUND: Hospital boards of directors can play a pivotal role in improving
      care, yet we know little about how the boards of hospitals that
      disproportionately serve minority patients engage in this issue. OBJECTIVES: To
      examine how boards of directors at black-serving hospitals are engaged in quality
      of care issues and compare priorities and practices of black-serving and non
      black-serving hospital boards. DESIGN: We identified all nonprofit U.S. hospitals
      in the top decile of proportion of elderly black patients ("black-serving") and
      surveyed their board chairpersons and a national sample of chairpersons from
      other nonprofit U.S. hospitals ("non-black-serving"). PARTICIPANTS: Board
      chairpersons of black-serving and non-black-serving U.S. hospitals. MAIN
      MEASURES: Board chairpersons' familiarity and expertise with quality of care
      issues, level of engagement with quality management, prioritization of quality
      issues, and efforts to improve quality or to reduce racial disparities in the
      quality of care. KEY RESULTS: We received responses from 79% of black-serving
      hospitals and 78% of non-black-serving hospitals. We found that board
      chairpersons from black-serving hospitals less often reported having at least
      moderate expertise in quality of care (68% versus 79%, P = 0.04) or rating it as
      one of the top two priorities for board oversight (48% versus 57%, P = 0.09) or
      for CEO performance evaluation (40% versus 50%, P = 0.05). Only 14.2% of board
      chairpersons from black-serving hospitals (and 7.7% of non-black-serving
      hospitals) agreed with the statement that disparities exist among my hospital
      patients, although less than 10% of all board chairpersons reported examining
      quality or patient satisfaction data stratified by race. CONCLUSIONS: Board
      chairpersons of black-serving hospitals report less expertise with quality of
      care issues and are less likely to give high priority to these issues than board
      chairpersons of non-black-serving hospitals. Interventions to engage and educate
      board members in issues of quality and racial disparities may be needed to
      improve quality and reduce disparities in care.

PMID- 21948205
TI  - Evaluation of the PHQ-9 Item 3 as a screen for sleep disturbance in primary care.
AB  - BACKGROUND: Sleep disturbance is a significant problem for adults presenting to
      primary care. Though it is recommended that primary care providers screen for
      sleep problems, a brief, effective screening tool is not available. OBJECTIVE:
      The aim of this preliminary study was to test the utility of item three of the
      Patient Health Questionnaire-9-item (PHQ-9) as a self-report screening test for
      sleep disturbance in primary care. DESIGN: This was a cross-sectional survey of
      male VA primary care patients in Syracuse and Rochester, NY. Sensitivity and
      specificity statistics were calculated as well as positive and negative
      predictive value to determine both whether the PHQ-9 item-3 can be used as an
      effective sleep screen in primary care and at what PHQ item-3 cut score patients
      should be further assessed for sleep disturbance. PARTICIPANTS: One hundred and
      eleven male, VA primary care patients over the age of 18 and without gross
      neurological impairment participated in this one-session, in-person study.
      MEASURES: During the research session, patients completed several questionnaires,
      including a basic demographic questionnaire, the PHQ-9, and the Insomnia Severity
      Index (ISI). KEY RESULTS: PHQ-9 item 3 significantly correlated with the total
      score on the ISI (r = 0.75, p < 0.0001). A cut score of 1 on the PHQ-9 item 3,
      indicating sleep disturbance at least several days in the last two weeks, showed
      the best balance of sensitivity (82.5%) and specificity (84.5%) as well as
      positive (78.4%) and negative (91%) predictive value. CONCLUSIONS: Item 3 of the
      PHQ-9 shows promise as a screener for sleep problems in primary care. Using this
      one-item of a popular screening measure for depression in primary care allows
      providers to easily screen for two important issues without unnecessarily adding
      significant burden.

PMID- 21948206
TI  - Traditional expectations versus US realities: first- and second-generation Asian
      Indian perspectives on end-of-life care.
AB  - BACKGROUND: Although end-of-life care preferences vary across racial/ethnic
      groups, little is known about how cultural values affect end-of-life care
      preferences among South Asian immigrants and their offspring in the US.
      OBJECTIVE: To examine the perspectives of first- and second-generation South
      Asians living in the US regarding end-of-life care. DESIGN: Focus group study.
      Discussions explored participant preferences and experiences with family members
      facing the end of life. PARTICIPANTS: Twelve first-generation and 11 second
      generation self-identified Asian Indians living in the mid-Atlantic region.
      APPROACH: Content analysis of focus group transcripts. RESULTS: First-generation
      participants ranged in age from 41 to 76 years and were evenly split by gender.
      Second-generation participants ranged in age from 23 to 36 years and included
      seven women and four men. All participants were highly educated, and two thirds
      were either studying or working in a health care field. All but two subjects were
      Hindu. Several themes emerged that highlighted cultural differences and
      challenges for this population in the context of end-of-life care: attitudes
      toward death and suffering; family duty; and preferences for information
      disclosure and decision making. Participants described cultural challenges due to
      the evolution of traditional roles, lack of explicit discussion between patients
      and family members about preferences and care expectations, and a tension between
      wanting to meet traditional expectations and the challenges in doing so given US
      social realities. CONCLUSIONS: Traditional cultural values, such as duty to
      family, greatly influenced end-of-life care preferences and retained importance
      across generations. Clinicians caring for Asian Indian patients at the end of
      life may be better able to assess care preferences after exploring the complex
      interplay between traditional expectations and specific social realities for each
      patient. Particular attention should be given to attitudes toward death and
      suffering, family duty, and preferences for information disclosure and decision
      making.

PMID- 21948207
TI  - Resident physician well-being and assessments of their knowledge and clinical
      performance.
AB  - BACKGROUND: Medical knowledge and clinical performance ratings are major criteria
      for assessing the competence of resident physicians. However, these assessments
      may be influenced by residents' mental health. The relationship between
      residents' well-being and empathy and assessments of their global performance
      remains unclear. OBJECTIVE: To determine whether resident well-being and empathy
      are associated with assessments of their medical knowledge and clinical
      performance. DESIGN, SETTING, AND PARTICIPANTS: We studied 730 clinical
      performance assessments completed by peers, supervising residents, and allied
      health professionals; 193 mini-clinical evaluation exercise (mini-CEX)
      evaluations; and 260 in-training examinations (ITE) of Mayo Clinic internal
      medicine residents between January 2009 and August 2010. Multivariate generalized
      estimating equations were used to evaluate associations between residents' well
      being and empathy and assessments of their knowledge and clinical performance.
      MEASUREMENTS: Independent variables were empathy using the Interpersonal
      Reactivity Index (IRI), burnout using the Maslach Burnout Inventory, depression
      using a standardized two-question screening instrument, and quality of life using
      a Linear Analog Self-Assessment item and the Medical Outcomes Study Short Form
      (SF-8). Dependent variables were mini-CEX, ITE, and the validated six-item Mayo
      clinical performance assessment. RESULTS: 202 residents (64.7%) provided both
      well-being and at least one category of assessment data. In multivariate models,
      residents' scores on the IRI empathy measure of "the tendency to adopt the
      psychological view of others" were associated with higher peer ratings on
      "desirability as a physician for a family member" (beta = 0.023, 95% CI = 0.007
      0.039, p = 0.004). Additionally, burnout was associated with higher supervisor
      ratings of communication (beta = 0.309, 95% CI = 0.100-0.517, p = 0.004). There
      were no observed associations between ITE or mini-CEX scores and resident quality
      of life, burnout, fatigue, depression, or empathy. CONCLUSIONS: Most dimensions
      of resident well-being were not associated with residents' knowledge scores and
      assessments of their clinical performance by other members of the health care
      team, which supports the trustworthiness of these measures. Nonetheless,
      correlations of resident empathy and burnout with assessments completed by peers
      and supervising residents suggest that some ratings of residents may be
      influenced by interpersonal factors.

PMID- 21948208
TI  - Bone development: overview of bone cells and signaling.
AB  - Vertebrates evolved elaborating a structure made up of more than 200 bones and
      cartilages articulated with one another to form the skeleton, through which
      locomotion, organ protection, lodging of hematopoiesis, and mineral homeostasis
      are allowed. Skeletogenesis starts at the fetal stage, along with marrow
      hematopoiesis, and evolves postnatally through modeling and remodeling processes
      that permit skeletal mass buildup. Preservation of skeletal mass is then
      implemented by balanced remodeling, which ensures continuous renovation of the
      tissue to allow its mechanical, structural, and metabolic properties to remain
      unaltered until ageing or diseases disrupt this equilibrium. Skeletal homeostasis
      is fulfilled by specialized bone cells in association with systemic and local
      regulators. Herein I review landmark discoveries that shed light on the intricate
      mesh connecting bone cells among themselves and with other systems, thus
      representing the cellular basis of normal and abnormal bone development and
      homeostasis.

PMID- 21948209
TI  - Nutrition, bone, and aging: an integrative physiology approach.
AB  - Osteoporosis, a condition associated with significant morbidity and mortality, is
      prevalent in the growing elderly population. Aging is associated with
      characteristic changes in the complex pathways of bone remodeling and in patterns
      of food intake. Whereas the traditional focus of nutritional supplementation for
      protection of bone health has centered around calcium and vitamin D, a multitude
      of nutrients have been identified with effects on bone, both individually and in
      combination. An integrative physiology approach can assist in formulating a
      deeper understanding of the complex interactions of nutrition and aging with
      bone, with the goal of identifying modifiable risk factors for the prevention of
      bone loss.

PMID- 21948211
TI  - Randomized clinical trial of fluid restriction in colorectal surgery.
AB  - BACKGROUND: Perioperative fluid therapy can influence postoperative hospital stay
      and complications after elective colorectal surgery. This trial was designed to
      examine whether an extremely restricted perioperative fluid protocol would reduce
      hospital stay beyond the existing fast-track hospital time of 7 days after
      surgery. METHODS: Patients were randomized to restricted or standard
      perioperative intravenous fluid regimens in a single-centre trial. Randomization
      was stratified for colonic, rectal, open and laparoscopic surgery. Patients were
      all treated within a fast-track protocol (careful preoperative preparation,
      optimal analgesia, early oral nutrition and early mobilization). The primary
      endpoint was length of postoperative hospital stay. The secondary endpoint was
      complications within 30 days. RESULTS: Seventy-nine patients were randomized to
      restricted and 82 to standard fluid therapy. Patients in the restricted group
      received a median of 3050 ml fluid on the day of surgery compared with 5775 ml in
      the standard group (P < 0.001). There was no difference between groups in primary
      hospital stay (median 6.0 days in both groups; P = 0.194) or stay including
      readmission (median 6.0 days in both groups; P = 0.158). The proportion of
      patients with complications was significantly lower in the restricted group (31
      of 79 versus 47 of 82; P = 0.027). Vasopressors were more often required in the
      restricted group (97 versus 80 per cent; P < 0.001). CONCLUSION: Restricted
      perioperative intravenous fluid administration does not reduce length of stay in
      a fast-track protocol.

PMID- 21948210
TI  - The Fanconi anemia pathway and DNA interstrand cross-link repair.
AB  - Fanconi anemia (FA) is an autosomal or X-linked recessive disorder characterized
      by chromosomal instability, bone marrow failure, cancer susceptibility, and a
      profound sensitivity to agents that produce DNA interstrand cross-link (ICL). To
      date, 15 genes have been identified that, when mutated, result in FA or an FA
      like syndrome. It is believed that cellular resistance to DNA interstrand cross
      linking agents requires all 15 FA or FA-like proteins. Here, we review our
      current understanding of how these FA proteins participate in ICL repair and
      discuss the molecular mechanisms that regulate the FA pathway to maintain genome
      stability.

PMID- 21948212
TI  - Morphological and biomechanical remodelling of the hepatic artery in a swine
      model of portal hypertension.
AB  - OBJECTIVES: To obtain the biomechanical and morphological remodelling of hepatic
      arteries in swine with portal hypertension. METHODS: A number of 20 white pigs
      was used, of which 14 were subjected to liver cirrhosis and portal hypertension
      (PHT) induced by carbon tetrachloride and pentobarbital; the rest were used as
      the control group. The biomechanical remodelling of the hepatic arteries was
      measured, namely, the incremental elastic modulus (E inc), pressure-strain
      elastic modulus (E p), volume elastic modulus (E v), the incremental compliance
      (C), the opening angle and the stained microstructural components of the vessels.
      RESULTS: The percentages for the microstructural components and the histologic
      data significantly changed in the experimental group, three incremental elastic
      moduli (E inc, E p, and E v) of the experimental group were significantly larger
      than those of the control group (P < 0.05); the compliance of hepatic arteries
      decreased greatly (P < 0.05) too. The opening angle (OA) was considerably larger
      than that of control group (P < 0.05). CONCLUSIONS: The study suggests that the
      morphological and biomechanical properties of swine hepatic arteries have changed
      significantly during the process of portal hypertension and that from
      biomechanical aspects, the hepatic arteries have also suffered from extensive
      remodelling, which in turn deteriorates the existing portal hypertension.

PMID- 21948214
TI  - Two sources of genetic liability to depression: interpreting the relationship
      between stress sensitivity and depression under a multifactorial polygenic model.
AB  - Psychopathology theories, clinical observations, and research all point to
      multiple sources of liability to depression. This article uses a longitudinal
      twin-study design to characterize the contribution of two genetically-influenced
      sources of depression risk: the first corresponding to stress sensitivity and the
      second representing risk that is independent of stress sensitivity. The sample
      consisted of 606 pairs of same-sex adolescent twins recruited from Beijing,
      China. Mean (SD) age at intake (Wave1) and follow-up (Wave2) was 13.2 (2.6) and
      15.1 (2.6) years, respectively. A Reaction Level index was developed to reflect
      individual differences in stress sensitivity. Biometric models were fit to
      examine the genetic influence on the variance of and covariance between stress
      sensitivity and depressive symptoms. Results showed that both Reaction Level and
      depressive symptoms were moderately heritable. The genetic correlation between
      depressive symptoms and Reaction Level was estimated to be .884. Genetic
      contributions to Reaction Level accounted for 37.5% of the total variance of
      depressive symptoms. Another set of genetic factors, which did not contribute to
      Reaction Level, accounted for 10.5% of the total variance of depressive symptoms.
      We interpret our results within the context of a multifactorial polygenic model,
      whereby depression risk is due to the combined contribution of multiple genetic
      and environmental factors.

PMID- 21948213
TI  - The evolution of function in strictosidine synthase-like proteins.
AB  - The exponential growth of sequence data provides abundant information for the
      discovery of new enzyme reactions. Correctly annotating the functions of highly
      diverse proteins can be difficult, however, hindering use of this information.
      Global analysis of large superfamilies of related proteins is a powerful strategy
      for understanding the evolution of reactions by identifying catalytic
      commonalities and differences in reaction and substrate specificity, even when
      only a few members have been biochemically or structurally characterized. A
      comparison of >2500 sequences sharing the six-bladed beta-propeller fold
      establishes sequence, structural, and functional links among the three subgroups
      of the functionally diverse N6P superfamily: the arylesterase-like and senescence
      marker protein-30/gluconolactonase/luciferin-regenerating enzyme-like (SGL)
      subgroups, representing enzymes that catalyze lactonase and related hydrolytic
      reactions, and the so-called strictosidine synthase-like (SSL) subgroup. Metal
      coordinating residues were identified as broadly conserved in the active sites of
      all three subgroups except for a few proteins from the SSL subgroup, which have
      been experimentally determined to catalyze the quite different strictosidine
      synthase (SS) reaction, a metal-independent condensation reaction. Despite these
      differences, comparison of conserved catalytic features of the arylesterase-like
      and SGL enzymes with the SSs identified similar structural and mechanistic
      attributes between the hydrolytic reactions catalyzed by the former and the
      condensation reaction catalyzed by SS. The results also suggest that despite
      their annotations, the great majority of these >500 SSL sequences do not catalyze
      the SS reaction; rather, they likely catalyze hydrolytic reactions typical of the
      other two subgroups instead. This prediction was confirmed experimentally for one
      of these proteins.

PMID- 21948215
TI  - Working memory and parent-rated components of attention in middle childhood: a
      behavioral genetic study.
AB  - The purpose of the current study was to investigate potential genetic and
      environmental correlations between working memory and three behavioral aspects of
      the attention network (i.e., executive, alerting, and orienting) using a twin
      design. Data were from 90 monozygotic (39% male) and 112 same-sex dizygotic (41%
      male) twins. Individual differences in working memory performance (digit span)
      and parent-rated measures of executive, alerting, and orienting attention
      included modest to moderate genetic variance, modest shared environmental
      variance, and modest to moderate nonshared environmental variance. As
      hypothesized, working memory performance was correlated with executive and
      alerting attention, but not orienting attention. The correlation between working
      memory, executive attention, and alerting attention was completely accounted for
      by overlapping genetic covariance, suggesting a common genetic mechanism or
      mechanisms underlying the links between working memory and certain parent-rated
      indicators of attentive behavior.

PMID- 21948216
TI  - Size separation of proteins by capillary zone electrophoresis with cationic
      hitchhiking.
AB  - The paper describes a method of size separation of proteins by capillary sieving
      electrophoresis with cationic surfactant. Proteins are separated within 12 min
      with repeatability of migration times better than 0.2%. Some proteins achieve the
      separation efficiency of 200,000 theoretical plates. The method can be used for
      determination of protein relative molecular masses. The accuracy of the
      determined relative molecular masses and the limitation of the method were
      investigated by the analysis of more than 60 proteins. The method also allows
      separation of protein oligomers. Proteins can be quantitated after the
      electrokinetic injection in the concentration range 0.07-0.43 g/L. The average
      detection limit is about 2 mg/L.

PMID- 21948217
TI  - Stem cells for retinal replacement therapy.
AB  - Retinal degenerative disease has limited therapeutic options and the possibility
      of stem cell-mediated regenerative treatments is being actively explored for
      these blinding retinal conditions. The relative accessibility of this central
      nervous system tissue and the ability to visually monitor changes after
      transplantation make the retina and adjacent retinal pigment epithelium prime
      targets for pioneering stem cell therapeutics. Prior work conducted for several
      decades indicated the promise of cell transplantation for retinal disease, and
      new strategies that combine these established surgical approaches with stem cell
      derived donor cells is ongoing. A variety of tissue-specific and pluripotent
      derived donor cells are being advanced to replace lost or damaged retinal cells
      and/or to slow the disease processes by providing neuroprotective factors, with
      the ultimate aim of long-term improvement in visual function. Clinical trials are
      in the early stages, and data on safety and efficacy are widely anticipated.
      Positive outcomes from these stem cell-based clinical studies would radically
      change the way that blinding disorders are approached in the clinic.

PMID- 21948218
TI  - Risk factors for discontinuing breastfeeding in southern Brazil: a survival
      analysis.
AB  - To identify risk factors for discontinuing breastfeeding during an infant's first
      year of life. A cohort study recruited mothers in a hospital in Sao Leopoldo,
      Brazil, which mainly serves the low-income population. In order to obtain
      socioeconomic, environmental, and behavioral information, face-to-face interviews
      with mothers were conducted after birth, and when their infants were 6 and 12
      months old. The duration of breastfeeding was investigated at 6 and 12 months,
      and recorded separately for each month. Depressive symptoms were assessed using
      the Beck Depression Inventory. The multivariate model for predicting the
      discontinuation of breastfeeding, adjusted Kaplan-Meier survival curves and Cox
      regression were used. Of the 360 participants, 201 (55.8%) discontinued
      breastfeeding within the first 12 months. A multivariate Cox regression model
      revealed that symptoms of maternal depression (low levels: RR = 1.59, 95% CI 1.02
      2.47; moderate to severe: RR = 2.03, 95% CI 1.35-3.01), bottle feeding (RR =
      2.07, 95% CI 1.31-3.28) and pacifier use in the first month of life (RR = 3.12,
      95% CI 2.13-4.57) were independently associated with the outcomes after adjusting
      for confounders. Breastfeeding cessation rates were lower for children who did
      not use bottle feeding or a pacifier in the first month of life and for the
      children whose mothers presented with minimal depression. Early pacifier use and
      bottle feeding must be strongly discouraged to support long-term breastfeeding.
      In addition, screening maternal depression at a primary care service can be a
      step forward in promoting a longer duration of breastfeeding.

PMID- 21948219
TI  - Analysis of breastfeeding policies and practices in childcare centres in
      Adelaide, South Australia.
AB  - Breastfeeding policies and practices were analysed in childcare settings in the
      metropolitan area of Adelaide, South Australia. Childcare centres were
      purposively selected based on their geographical location, type and socioeconomic
      score of the area. Qualitative inquiry approach was employed by undertaking
      interviews with childcare centres' director or baby house coordinator to explore
      their perception towards breastfeeding practice and support within their centre.
      Breastfeeding related policy documents, where available, were also collected
      during the interviews to triangulate data. A total of 15 face-to-face interviews
      were conducted. Six childcare centres had a written policy specifically on
      breastfeeding support, although the technical issues of handling breastmilk were
      included in most centres' food and nutrition guidelines. Most participants
      believed that decision to breastfeed is the personal choice of parents, and hence
      saw the childcare centre's role as supporting parental choice whether it is
      breastfeeding or not. The provision of physical space to breastfeed and
      facilities to store the expressed breast milk were the most common practices in
      support of parents who had chosen to continue breastfeeding. Participants
      perceived mothers' work-related issues such as distance from the centre, time,
      and unsupportive workplace the most important barriers that led to early
      introduction of bottle feeding or breastfeeding cessation. Most childcare centres
      support breastfeeding in a more passive than active way. Breastfeeding promotion
      needs to be an integral part of childcare centres training, policy and practice
      if an increased rate of breastfeeding is to be achieved particularly amongst
      working mothers.

PMID- 21948220
TI  - BRAF(V600E) mutation analysis from May-Grunwald Giemsa-stained cytological
      samples as an adjunct in identification of high-risk papillary thyroid carcinoma.
AB  - The BRAF(V600E) mutation is specific for thyroid papillary cancer (PTC) and
      correlates with PTCs invasiveness. This study investigated whether detection of
      BRAF(V600E) mutation can be performed on routinely stained FNABs. We also
      examined if establishment of the BRAF(V600E) mutation could help in
      identification of patients at higher risk for metastatic disease. DNA was
      isolated from 134 FNABs samples (20 follicular neoplasm, ten suspicious for
      malignancy, and 104 malignant) using Pinpoint Slide DNA Isolation System.
      BRAF(V600E) mutation was detected by PCR followed by sequencing. DNA was
      successfully extracted from all examined FNABs samples. In follicular neoplasm,
      suspicious for malignancy and malignant FNABs, BRAF(V600E) mutation was found in
      0/20 (0%), 2/10 (20%), and 47/104 (45.2%) of cases, respectively. Extra-thyroidal
      extension was detected in 35/47 (74.4%) BRAF(V600E) positive and in 24/57 (42.1%)
      wild-type BRAF cases (p = 0.001). Metastases were detected in 37/47 (78.7%)
      BRAF(V600E) positive and in 28/57 (49.1%) wild-type BRAF cases (p = 0.002). Our
      results showed that stained FNAB specimens can be used for DNA extraction and
      assessment of BRAF(V600E) mutation. Detection of BRAF(V600E) mutation had limited
      value in diagnoses of malignancy in follicular neoplasms but can ascertain
      malignancy in subset of suspicious for malignancy FNABs. In malignant FNABs,
      BRAF(V600E) mutation was significantly associated with presence of extra
      thyroidal extension and metastases after surgery.

PMID- 21948221
TI  - Chemical defense across three trophic levels: Catalpa bignonioides, the
      caterpillar Ceratomia catalpae, and its endoparasitoid Cotesia congregata.
AB  - Plant secondary chemistry can vary among plant tissues, individuals, and
      populations, and this variation has population-level consequences for upper
      trophic levels. In this study, we examined the multi-trophic consequences of
      variation in iridoid glycosides, which are a component of plant defense against
      generalist herbivores and also contribute to the unpalatability of sequestering
      herbivores to both vertebrate and invertebrate predators. Several populations of
      Catalpa bignonioides were located and examined for the presence of the Catalpa
      Sphinx, Ceratomia catalpae, a specialist herbivore of Catalpa. We quantified
      iridoid glycoside content in Catalpa Sphinx caterpillars and in damaged and
      undamaged C. bignonioides leaves. Overall, leaves of C. bignonioides that were
      damaged by Catalpa Sphinx caterpillars contained lower concentrations of two
      major iridoid glycosides, catalpol and catalposide, than leaves of undamaged
      trees from naturally occurring populations. Catalpa Sphinx caterpillars sequester
      only catalpol, and increasing catalpol and catalposide concentrations in leaves
      were associated with increased catalpol sequestration by caterpillars. The
      parasitoid Cotesia congregata develops successfully inside catalpol-sequestering
      Catalpa Sphinx caterpillars, and we examined parasitoid larvae for the presence
      of catalpol. Parasitoid larvae dissected from caterpillars contained catalpol,
      but at lower concentrations than their host caterpillars. The variation in
      chemical defense documented here has rarely been documented over multiple trophic
      levels, but such resolved systems are ideal for examining competing hypotheses
      about the effects of plant secondary metabolites on higher trophic levels.

PMID- 21948222
TI  - Rise of herbal and traditional medicine in erectile dysfunction management.
AB  - Herbal medicine long has been used in the management of sexual dysfunction,
      including erectile dysfunction. Many patients have attested to the efficacy of
      this treatment. However, is it evidence-based medicine? Studies have been done on
      animal models, mainly in the laboratory. However, randomized controlled trials on
      humans are scarce. The only herbal medications that have been studied for
      erectile dysfunction are Panax ginseng, Butea superba, Epimedium herbs (icariin),
      Tribulus terrestris, Securidaca longipedunculata, Piper guineense, and yohimbine.
      Of these, only Panax ginseng, B. superb, and yohimbine have published studies
      done on humans. Unfortunately, these published trials on humans were not robust.
      Many herbal therapies appear to have potential benefits, and similarly, the
      health risks of various phytotherapeutic compounds need to be elucidated.
      Properly designed human trials should be worked out and encouraged to determine
      the efficacy and safety of potential phytotherapies.

PMID- 21948224
TI  - Snakebite: not neglected but frequently hijacked.

PMID- 21948223
TI  - Risk factors for predicting diarrheal duration and morbidity in children with
      acute diarrhea.
AB  - OBJECTIVE: To identify baseline risk factors for prolonged diarrheal duration and
      subsequent complications in children aged 6 to 59 mo with acute diarrhea who
      participated in a micronutrient clinical trial in a tertiary care hospital.
      METHODS: The adjusted odds ratio or incidence risk ratios (IRR) of the baseline
      variables for prolongation of diarrheal duration (cox proportional hazard model),
      diarrhea >7 d (multiple logistic regressions), severe dehydration experienced
      after hospitalization (poisson regression models) was estimated. RESULTS: Fever
      (OR 1.10, 95% CI 1.02-1.19, p = 0.02), dehydration (OR 1.32, 95% CI 1.10-1.59, p
      = 0.003), dysentery (OR 1.41 95% CI 1.09-1.82, p = 0.008), those who received
      medications (OR 1.19, 95% CI 1.03-1.39, p = 0.02), and weight for age Z-score <=2
      (OR 1.25, 95% CI 1.07-1.46, p = 0.004) were at a greater risk of prolonged
      diarrhea. Diarrhea >7 d was associated with younger age (OR 1.08, 95% CI 1.03
      1.14, p = 0.003), female child (OR 2.33, 95% CI 1.19-4.55, p = 0.013), diarrheal
      duration before enrolment (OR 1.06, 95% CI 1.04-1.09, p < 0.001), fever (OR 1.7,
      95% CI 1.23-2.49, p = 0.002) and the weight for age Z-score <=2 (OR 4.32, 95% CI
      2.03-9.16, p < 0.001). Severe dehydration after hospitalization was associated
      with dehydration at baseline (OR 6.7, 95% CI 2-3.0, p < 0.001), incomplete
      immunization (OR 3.33, 95% CI 1.5-7.69, p < 0.001), failure to receive any
      medication(OR 3.03, 95% CI 1.26-7.14, p = 0.01). CONCLUSIONS: Few studies assess
      risk factors for diarrheal morbidity prospectively. The present study showed that
      children of acute diarrhea with above risk factors need stricter monitoring for
      complications to reduce diarrheal mortality.

PMID- 21948226
TI  - Ethics consultation and empathy : finding the balance in clinical settings.
AB  - There is no doubt that emotions have an important effect on practices of moral
      reasoning such as clinical ethics consultation. Empathy is not only a basic human
      emotion but also an important and learnable skill for health care professionals.
      A basic amount of empathy is essential both in patient care and in clinical
      ethics consultation. This article debates the "adequate dose" of empathy in
      ethics consultations in clinical settings and tries to identify possible
      situations within the process of consultation in which this crucial feeling is at
      risk.

PMID- 21948225
TI  - Preferences for colorectal cancer screening tests and screening test use in a
      large multispecialty primary care practice.
AB  - BACKGROUND: The purpose of this study was to identify factors associated with
      colorectal cancer (CRC) screening test preference and examine the association
      between test preference and test completed. METHODS: Patients (n = 1224) were 50
      70 years, at average CRC risk, and overdue for screening. Outcome variables were
      preference for fecal occult blood test (FOBT), colonoscopy (COL), sigmoidoscopy
      (SIG), or barium enema (BE), measured by telephone survey, and concordance
      between test preference and test completed assessed using medical records.
      RESULTS: Thirty-five percent preferred FOBT, 41.1% COL, 12.7% SIG, and 5.7% BE.
      Preference for SIG or COL was associated with having a physician recommendation,
      greater screening readiness, test-specific self-efficacy, greater CRC worry, and
      perceived pros of screening. Preference for FOBT was associated with self
      efficacy for doing FOBT. Participants who preferred COL were more likely to
      complete COL compared with those who preferred another test. Of those screened,
      only 50% received their preferred test. Those not receiving their preferred test
      most often received COL (52%). CONCLUSIONS: Lack of concordance between patient
      preference and test completed suggests that patients' preferences are not well
      incorporated into screening discussions and test decisions, which could
      contribute to low screening uptake. Physicians should acknowledge patients'
      preferences when discussing test options and making recommendations, which may
      increase patients' receptivity to screening.

PMID- 21948227
TI  - Gratitude's renewal.

PMID- 21948228
TI  - Effects of a focused patient-centered care curriculum on the experiences of
      internal medicine residents and their patients.
AB  - BACKGROUND: Traditional residency training may not promote competencies in
      patient-centered care. AIM: To improve residents' competencies in delivering
      patient-centered care. SETTING/PARTICIPANTS: Internal medicine residents at a
      university-based teaching hospital in Baltimore, Maryland. PROGRAM DESCRIPTION:
      One inpatient team admitted half the usual census and was exposed to a multi
      modal patient-centered care curriculum to promote knowledge of patients as
      individuals, improve patient transitions of care, and reduce barriers to
      medication adherence. PROGRAM EVALUATION: Annual resident surveys (N = 40)
      revealed that the intervention was judged as professionally valuable (90%) and
      important to their training (90%) and offered experiences not available during
      other rotations (88%). Compared to standard inpatient rotation evaluations (n =
      163), intervention rotation evaluations (n = 51) showed no differences in ratings
      for traditional medical learning, but higher ratings for improving how housestaff
      address patient medication adherence, communicate with patients about post
      hospital transition of care, and know their patients as people (all p < 0.01). On
      post-discharge surveys, patients from the intervention team (N = 177, score 90.4,
      percentile ranking 97%) reported greater satisfaction with physicians than
      patients on standard teams (N = 924, score 86.1, percentile ranking 47%) p <
      0.01). DISCUSSION: A patient-centered inpatient curriculum was associated with
      higher satisfaction ratings in patient-centered domains by internal medicine
      residents and with higher satisfaction ratings of their physicians by patients.
      Future research will explore the intervention's impact on clinical outcomes.

PMID- 21948229
TI  - Improving participant feedback to continuing medical education presenters in
      internal medicine: a mixed-methods study.
AB  - BACKGROUND: Feedback is essential for improving the skills of continuing medical
      education (CME) presenters. However, there has been little research on improving
      the quality of feedback to CME presenters. OBJECTIVES: To validate an instrument
      for generating balanced and behavior-specific feedback from a national cross
      section of participants to presenters at a large internal medicine CME course.
      DESIGN, SETTING, AND PARTICIPANTS: A prospective, randomized validation study
      with qualitative data analysis that included all 317 participants at a Mayo
      Clinic internal medicine CME course in 2009. MEASUREMENTS: An 8-item (5-point
      Likert scales) CME faculty assessment enhanced study form (ESF) was designed
      based on literature and expert review. Course participants were randomized to a
      standard form, a generic study form (GSF), or the ESF. The dimensionality of
      instrument scores was determined using factor analysis to account for clustered
      data. Internal consistency and interrater reliabilities were calculated.
      Associations between overall feedback scores and presenter and presentation
      variables were identified using generalized estimating equations to account for
      multiple observations within talk and speaker combinations. Two raters reached
      consensus on qualitative themes and independently analyzed narrative entries for
      evidence of balanced and behavior-specific comments. RESULTS: Factor analysis of
      5,241 evaluations revealed a uni-dimensional model for measuring CME presenter
      feedback. Overall internal consistency (Cronbach alpha = 0.94) and internal
      consistency reliability (ICC range 0.88-0.95) were excellent. Feedback scores
      were associated with presenters' academic ranks (mean score): Instructor (4.12),
      Assistant Professor (4.38), Associate Professor (4.56), Professor (4.70) (p =
      0.046). Qualitative analysis revealed that the ESF generated the highest numbers
      of balanced comments (GSF = 11, ESF = 26; p = 0.01) and behavior-specific
      comments (GSF = 64, ESF = 104; p = 0.001). CONCLUSIONS: We describe a practical
      and validated method for generating balanced and behavior-specific feedback for
      CME presenters in internal medicine. Our simple method for prompting course
      participants to give balanced and behavior-specific comments may ultimately
      provide CME presenters with feedback for improving their presentations.

PMID- 21948230
TI  - Is it downhill from here? Eliminating leukemic stem cells and curing chronic
      myeloid leukemia.
AB  - Patients with chronic phase chronic myeloid leukemia who respond to imatinib have
      a rapid initial decrease in BCR-ABL transcript levels (alpha), followed by a slow
      decline (beta). The rate of beta decrease is consistent with declining leukemic
      stem cells and may predict which patients may safely discontinue therapy.

PMID- 21948231
TI  - Neutrophil degranulation and immunosuppression in patients with GBM: restoration
      of cellular immune function by targeting arginase I.
AB  - PURPOSE: The source of glioblastoma (GBM)-associated immunosuppression remains
      multifactorial. We sought to clarify and therapeutically target myeloid cell
      derived peripheral immunosuppression in patients with GBM. EXPERIMENTAL DESIGN:
      Direct ex vivo T-cell function, serum Arginase I (ArgI) levels, and circulating
      myeloid lineage populations were compared between patients with GBM and normal
      donors or patients with other intracranial tumors. Immunofunctional assays were
      conducted using bulk and sorted cell populations to explore the potential
      transfer of myeloid cell-mediated immunosuppression and to identify a potential
      mechanism for these effects. ArgI-mediated immunosuppression was therapeutically
      targeted in vitro through pharmacologic inhibition or arginine supplementation.
      RESULTS: We identified a significantly expanded population of circulating,
      degranulated neutrophils associated with elevated levels of serum ArgI and
      decreased T-cell CD3zeta expression within peripheral blood from patients with
      GBM. Sorted CD11b(+) cells from patients with GBM were found to markedly suppress
      normal donor T-cell function in coculture, and media harvested from mitogen
      stimulated GBM peripheral blood mononuclear cell (PBMC) or GBM-associated mixed
      lymphoid reactions showed ArgI levels that were significantly higher than
      controls. Critically, T-cell suppression in both settings could be completely
      reversed through pharmacologic ArgI inhibition or with arginine supplementation.
      CONCLUSIONS: These data indicate that peripheral cellular immunosuppression in
      patients with GBM is associated with neutrophil degranulation and elevated levels
      of circulating ArgI, and that T-cell function can be restored in these
      individuals by targeting ArgI. These data identify a novel pathway of GBM
      mediated suppression of cellular immunity and offer a potential therapeutic
      window for improving antitumor immunity in affected patients.

PMID- 21948232
TI  - Molecular imaging of TGFbeta-induced Smad2/3 phosphorylation reveals a role for
      receptor tyrosine kinases in modulating TGFbeta signaling.
AB  - PURPOSE: The dual modality of TGFbeta, both as a potent tumor suppressor and a
      stimulator of tumor progression, invasion, and metastasis, make it a critical
      target for therapeutic intervention in human cancers. The ability to carry out
      real-time, noninvasive imaging of TGFbeta-activated Smad signaling in live cells
      and animal models would significantly improve our understanding of the regulation
      of this unique signaling cascade. To advance these efforts, we developed a highly
      sensitive molecular imaging tool that repetitively, noninvasively, and
      dynamically reports on TGFBR1 kinase activity. EXPERIMENTAL DESIGN: The
      bioluminescent TGFbetaR1 reporter construct was developed using a split firefly
      luciferase gene containing a functional sensor of Smad2 phosphorylation, wherein
      inhibition of TGFbeta receptor1 kinase activity leads to an increase in reporter
      signaling. The reporter was stably transfected into mammalian cells and used to
      image in vivo and in vitro bioluminescent activity as a surrogate for monitoring
      TGFBR1 kinase activity. RESULTS: The reporter was successfully used to monitor
      direct and indirect inhibition of TGFbeta-induced Smad2 and SMAD3 phosphorylation
      in live cells and tumor xenografts and adapted for high-throughput screening, to
      identify a role for receptor tyrosine kinase inhibitors as modulators of TGFbeta
      signaling. CONCLUSION: The reporter is a dynamic, noninvasive imaging modality
      for monitoring TGFbeta-induced Smad2 signaling in live cells and tumor
      xenografts. It has immense potential for identifying novel effectors of R-Smad
      phosphorylation, for validating drug-target interaction, and for studying TGFbeta
      signaling in different metastasis models.

PMID- 21948233
TI  - ALK mutations conferring differential resistance to structurally diverse ALK
      inhibitors.
AB  - PURPOSE: EML4-ALK fusions define a subset of lung cancers that can be effectively
      treated with anaplastic lymphoma kinase (ALK) inhibitors. Unfortunately, the
      duration of response is heterogeneous and acquired resistance limits their
      ultimate efficacy. Thus, a better understanding of resistance mechanisms will
      help to enhance tumor control in EML4-ALK-positive tumors. EXPERIMENTAL DESIGN:
      By applying orthogonal functional mutagenesis screening approaches, we screened
      for mutations inducing resistance to the aminopyridine PF02341066 (crizotinib)
      and/or the diaminopyrimidine TAE684. RESULTS: Here, we show that the resistance
      mutation, L1196M, as well as other crizotinib resistance mutations (F1174L and
      G1269S), are highly sensitive to the structurally unrelated ALK inhibitor TAE684.
      In addition, we identified two novel EML4-ALK resistance mutations (L1198P and
      D1203N), which unlike previously reported mutations, induced resistance to both
      ALK inhibitors. An independent resistance screen in ALK-mutant neuroblastoma
      cells yielded the same L1198P resistance mutation but defined two additional
      mutations conferring resistance to TAE684 but not to PF02341066. CONCLUSIONS: Our
      results show that different ALK resistance mutations as well as different ALK
      inhibitors impact the therapeutic efficacy in the setting of EML4-ALK fusions and
      ALK mutations.

PMID- 21948235
TI  - Palermo-2010 conference on biogerontology.

PMID- 21948234
TI  - Phase I trial of adoptive cell transfer with mixed-profile type-I/type-II
      allogeneic T cells for metastatic breast cancer.
AB  - PURPOSE: Metastatic breast cancer (MBC) response to allogeneic lymphocytes
      requires donor T-cell engraftment and is limited by graft-versus-host disease
      (GVHD). In mice, type-II-polarized T cells promote engraftment and modulate GVHD,
      whereas type-I-polarized T cells mediate more potent graft-versus-tumor (GVT)
      effects. This phase I translational study evaluated adoptive transfer of ex vivo
      costimulated type-I/type-II (T1/T2) donor T cells with T-cell-depleted (TCD)
      allogeneic stem cell transplantation (AlloSCT) for MBC. EXPERIMENTAL DESIGN:
      Patients had received anthracycline, taxane, and antibody therapies, and been
      treated for metastatic disease and a human leukocyte antigen (HLA)-identical
      sibling donor. Donor lymphocytes were costimulated ex vivo with anti-CD3/anti
      CD28 antibody-coated magnetic beads in interleukin (IL)-2/IL-4-supplemented
      media. Patients received reduced intensity conditioning, donor stem cells and
      T1/T2 cells, and monitoring for toxicity, engraftment, GVHD, and tumor response;
      results were compared with historical controls, identically treated except for
      T1/T2 product infusions. RESULTS: Mixed type-I/type-II CD4(+) T cells
      predominated in T1/T2 products. Nine patients received T1/T2 cells at dose level
      1 (5 * 10(6) cells/kg). T-cell donor chimerism reached 100% by a median of 28
      days. Seven (78%) developed acute GVHD. At day +28, five patients had partial
      responses (56%) and none had MBC progression; thereafter, two patients had
      continued responses. Donor T-cell engraftment and tumor responses appeared faster
      than in historical controls, but GVHD rates were similar and responders
      progressed early, often following treatment of acute GVHD. CONCLUSION: Allogeneic
      T1/T2 cells were safely infused with TCD-AlloSCT, appeared to promote donor
      engraftment, and may have contributed to transient early tumor responses.

PMID- 21948236
TI  - Letter regarding Guddat et al. "Fatal spontaneous subdural bleeding due to
      neonatal giant cell hepatitis: a rare differential diagnosis of shaken baby
      syndrome".

PMID- 21948237
TI  - Fast preparation of monolithic immobilized pH gradient column by
      photopolymerization and photografting techniques for isoelectric focusing
      separation of proteins.
AB  - A new method was developed to prepare monolithic immobilized pH gradient (M-IPG)
      columns in UV-transparent fused-silica capillaries by the 5-min
      photopolymerization of acrylamide and N,N'-methylenebisacrylamide, followed by
      the 20-min photografting of the focused ampholine-derived glycidylmethacrylate
      monomer on the monolithic matrix, by which the preparation time was reduced, and
      the stability of the formed pH gradient was improved, compared with our previous
      methods. Using the prepared M-IPG column, the baseline separation of proteins was
      achieved according to their pIs. Without carrier ampholytes added in the running
      buffer, the separated components could be detected with high sensitivity by UV at
      low wavelength.

PMID- 21948238
TI  - Structural basis of glaucoma: the fortified astrocytes of the optic nerve head
      are the target of raised intraocular pressure.
AB  - Increased intraocular pressure (IOP) damages the retinal ganglion cell axons as
      they pass through the optic nerve head (ONH). The massive connective tissue
      structure of the human lamina cribrosa is generally assumed to be the pressure
      transducer responsible for the damage. The rat, however, with no lamina cribrosa,
      suffers the same glaucomatous response to raised IOP. Here, we show that the
      astrocytes of the rat ONH are "fortified" by extraordinarily dense cytoskeletal
      filaments that would make them ideal transducers of distorting mechanical forces.
      The ONH astrocytes are arranged as a fan-like radial array, firmly attached
      ventrally to the sheath of the ONH by thick basal processes, but dividing
      dorsally into progressively more slender processes with only delicate attachments
      to the sheath. At 1 week after raising the IOP by an injection of magnetic
      microspheres into the anterior eye chamber, the fine dorsal processes of the ONH
      astrocytes are torn away from the surrounding sheath. There is no indication of
      distortion or compression of the axons. Subsequently, despite return of the IOP
      toward normal levels, the damage to the ONH progresses ventrally through the
      astrocytic cell bodies, resulting in complete loss of the fortified astrocytes
      and of the majority of the axons by around 4 weeks. We propose that the dorsal
      attachments of the astrocytes are the site of initial damage in glaucoma, and
      that the damage to the axons is not mechanical, but is a consequence oflocalized
      loss of metabolic support from the astrocytes (Tsacopoulos and Magistretti (1996)
      J Neurosci 16:877-885).

PMID- 21948239
TI  - CTCF and cohesin cooperatively mediate the cell-type specific interchromatin
      interaction between Bcl11b and Arhgap6 loci.
AB  - CCCTC-binding factor (CTCF) is a master organizer of genome spatial organization
      and plays an important role in mediating extensive chromatin interactions.
      Circular chromosome conformation capture (4C) is a high-throughput approach that
      allows genome-wide screening for unknown potential interaction partners. Using a
      conserved CTCF binding site on the Bcl11b locus as bait, an interaction partner
      at the Arhgap6 locus on a different chromosome was identified by 4C. Additional
      experiments verified that the interchromatin interaction between the Bcl11b and
      Arhgap6 loci was cell-type specific, which was cooperatively mediated by CTCF and
      cohesin. Functional analysis showed that the interchromatin interaction partners
      were repressing regulatory elements. These results indicate that interaction
      chromatin loops regulate the expression of the relevant genes.

PMID- 21948240
TI  - Pharmacokinetics of natural borneol after oral administration in mice brain and
      its effect on excitation ratio.
AB  - Previous studies have indicated that borneol has double side effects on the
      central nervous system (CNS), but the mechanism is unknown. The aim of this study
      was to clarify the relationship between excitation ratio [contents of excitatory
      amino acids (AAs) versus that of inhibitory] and the content of natural borneol
      after a single oral dose. Mice were administered a 1.2 g/kg dose of natural
      borneol (containing 98% D: -borneol) by oral ingestion. Brain samples were
      collected before administration and at 0.083, 0.167, 0.25, 0.333, 0.5, 0.75, 1,
      1.5, 2, 2.5, 3, 4 and 5 h after administration. The brain concentration of
      natural borneol and contents of AA neurotransmitters in mice brain were
      determined by GC-MS and HPLC-FLU, respectively. After per oral application,
      natural borneol was absorbed rapidly into the brain and could be determined 5 min
      after dosing. The maximal brain concentration (86.52 MUg/g) was reached after 1 h
      post-dosing. Natural borneol could affect the contents of AA neurotransmitters in
      mice brain: L: -aspartic acid increased significantly from 0.083 to 1 h after
      administration, L: -glutamic acid increased significantly at 0.333 h and
      decreased from 1.5 to 5 h, gamma-amino-N-butyric acid increased significantly
      from 0.167 to 5 h, whereas glycine was not affected. The excitation ratio is the
      contents of excitatory AAs versus that of inhibitory AAs, which reflects the
      excitatory or inhibitory state of the body. The excitation ratio elevated
      transitorily and then declined 0.5 h post-dosing; there were significant
      differences between 1.5-5 h post-dose compared with pre-dose. The present study
      indicated that natural borneol could affect the contents of AA neurotransmitters,
      and the change in excitatory ratio led to borneol's double side effects on the
      CNS.

PMID- 21948241
TI  - Sustaining engineering codes of ethics for the twenty-first century.
AB  - How much responsibility ought a professional engineer to have with regard to
      supporting basic principles of sustainable development? While within the United
      States, professional engineering societies, as reflected in their codes of
      ethics, differ in their responses to this question, none of these professional
      societies has yet to put the engineer's responsibility toward sustainability on a
      par with commitments to public safety, health, and welfare. In this paper, we aim
      to suggest that sustainability should be included in the paramountcy clause
      because it is a necessary condition to ensure the safety, health, and welfare of
      the public. Part of our justification rests on the fact that to engineer
      sustainably means among many things to consider social justice, understood as the
      fair and equitable distribution of social goods, as a design constraint similar
      to technical, economic, and environmental constraints. This element of social
      justice is not explicit in the current paramountcy clause. Our argument rests on
      demonstrating that social justice in terms of both inter- and intra-generational
      equity is an important dimension of sustainability (and engineering). We also
      propose that embracing sustainability in the codes while recognizing the role
      that social justice plays may elevate the status of the engineer as public
      intellectual and agent of social good. This shift will then need to be
      incorporated in how we teach undergraduate engineering students about engineering
      ethics.

PMID- 21948242
TI  - Olfactory cue mediated neonatal recognition in sheep, Ovis aries.
AB  - The strong bond between ewe and lamb formed shortly after parturition is an
      important factor in lamb survival. Evidence exists that a ewe can distinguish her
      lamb by its unique smell, but the constituents of such a putative olfactory cue
      have not yet been identified. We have now identified 133 volatile organic
      compounds associated with the wool of Dohne Merino lambs that we presume may be
      involved in neonatal recognition. Quantitative analysis and comparison of odor
      profiles of the twins of 16 ewes (9.69% sample group) of a flock of 165 twin
      bearing ewes revealed that the wool volatiles of twins are qualitatively and
      quantitatively similar, but differ from those of other twins or non-twin lambs in
      the flock. The 88 constituents present in at least 20% of the analyzed wool
      samples were considered as variables for multivariate analysis. A P-value < 0.001
      was calculated, indicating that the pairing of twins according to the qualitative
      and quantitative composition of the wool was significant. Bioassays carried out
      during the lambing seasons of 2009 and 2010 confirmed the previously established
      role of lamb odor in ewe-lamb recognition. However, when alien lambs were dressed
      in jackets sprayed with synthetic mixtures formulated to match the chemical
      composition of the effluvia of the ewes' own lambs, ewes rejected the aliens.
      This is possibly because the VOCs were not released in quantitative ratios
      sufficiently accurate to emulate the odor of the ewes' own lambs.

PMID- 21948243
TI  - Colonic-type adenocarcinoma of the base of the tongue: a case report of a rare
      neoplasm.
AB  - Lingual adenocarcinomas (ADC), either primary or metastatic to the tongue are
      extraordinarily rare neoplasms. Primary lingual adenocarcinomas are primarily of
      minor salivary gland origin. Two cases of primary colonic-type adenocarcinomas of
      the base of the tongue were recently reported for the first time in the English
      literature. We present an additional case of lingual intestinal-type
      adenocarcinoma with mucinous features that occurred in association with cervical
      node metastasis and discuss the clinicopathologic features and histogenetic
      aspects of this rare entity.

PMID- 21948245
TI  - Correlations between EEG and clinical outcome in chronic neuropathic pain:
      surgical effects and treatment resistance.
AB  - Chronic neuropathic pain may require a neurosurgical treatment, but for reasons
      that have not been fully explored yet, a significant number of patients do not
      benefit from the intervention. We compared the resting EEG of 15 healthy controls
      to the EEG of 23 chronic neuropathic pain patients before and 12 months after
      treatment by the central lateral thalamotomy (CLT). A patient subgroup had a high
      (n = 14, pain relief (PR)  >= 50%) and another subgroup a low (n = 9, PR < 50%)
      postoperative PR. EEG spectral power and source localization of the high PR
      patients were normalized postoperatively. In contrast, low PR patients showed
      postoperative maintenance of insular, cingulate and prefrontal overactivities,
      and their frustration values were positively correlated with cingulate and
      prefrontal activity. These findings demonstrate a normalizing effect of CLT on
      cortical activity and suggest that treatment resistance is associated with a
      frustration-based dynamics.

PMID- 21948244
TI  - Expression of the vascular endothelial growth factor and angiopoietins in
      mucoepidermoid carcinoma of salivary gland.
AB  - Disrupted coordination of angiogenesis regulating signals, among them the
      vascular endothelial growth factor (VEGF) and angiopoietins (Angs), has been
      associated with abnormal angiogenesis and tumor progression. While VEGF induces
      endothelial cell proliferation, thereby initiating vessel formation, Angs are
      subsequently required for mural cell attachment, thus influencing remodeling and
      maturation of this vasculature. In addition to tumor cell, endothelial and mural
      cells, as well as myofibroblasts may also contribute to the secretion of these
      factors. In this study, we have analyzed by immunohistochemistry the expression
      of VEGF, Ang-1, Ang-2 and the Angs receptor Tie2 in both the stroma and tumor
      cells of mucoepidermoid carcinoma (MEC) of salivary gland. We have demonstrated
      that when myofibroblasts were detected adjacent to the cancer cells, they were
      frequently associated with intense positive staining for Ang-1 and Ang-2, and no
      reactivity to VEGF and Tie2. These myofibroblast-rich Ang-1 and Ang-2-stained
      areas were more commonly found in high-grade MEC cases than in low-grade ones. As
      for the malignant cells, they frequently expressed all proteins studied, but Ang
      2 and VEGF were detected at higher levels compared to Ang-1 and Tie2. Our results
      indicate that the MEC environment favors cooperative activity between Angs and
      VEGF in modulating vascular growth and tumor aggressiveness.

PMID- 21948247
TI  - Exercise during pregnancy mitigates Alzheimer-like pathology in mouse offspring.
AB  - Physical activity protects brain function in healthy individuals and those with
      Alzheimer's disease (AD). Evidence for beneficial effects of parental exercise on
      the health status of their progeny is sparse and limited to nondiseased
      individuals. Here, we questioned whether maternal running interferes with
      offspring's AD-like pathology and sought to decipher the underlying mechanisms in
      TgCRND8 mice. Maternal stimulation was provided by voluntary wheel running vs.
      standard housing during pregnancy. Following 5 mo of standard housing of
      transgenic and wild-type offspring, their brains were examined for AD-related
      pathology and/or plasticity changes. Running during pregnancy reduced beta
      amyloid (Abeta) plaque burden (-35%, P=0.017) and amyloidogenic APP processing in
      transgenic offspring and further improved the neurovascular function by
      orchestrating different Abeta transporters and increasing angiogenesis (+29%,
      P=0.022). This effect was accompanied by diminished inflammation, as indicated by
      reduced microgliosis (-20%, P=0.002) and down-regulation of other proinflammatory
      mediators, and resulted in less oxidative stress, as nitrotyrosine levels
      declined (-28%, P=0.029). Moreover, plasticity changes (in terms of up-regulation
      of reelin, synaptophysin, and ARC) were found not only in transgenic but also in
      wild-type offspring. We conclude that exercise during pregnancy provides long
      lasting protection from neurodegeneration and improves brain plasticity in the
      otherwise unstimulated progeny.

PMID- 21948248
TI  - "If he had 40 cents he'd buy matches instead of lollies": motivational factors in
      a sample of New Zealand adolescent firesetters.
AB  - Motivation has been proposed as an important factor in both the causality and
      subsequent treatment of juveniles who deliberately light fires. Thus, a wide
      range of research has previously been completed, investigating such motives. This
      research has resulted in the creation of classifications of firesetting motives
      and behaviours, all of which fit upon a continuum of motivational categories
      ranging from curiosity or match play, through to deliberate delinquent acts. This
      current study aimed to gain insight into how both firesetters and their
      caregivers perceived firesetting motivation. A total of 18 male youths, who had
      engaged in deliberate firesetting, and 13 parents were interviewed. Qualitative
      analysis gathered from interviews with adolescent participants reported
      personality and individual characteristic themes, the most frequent of these
      being anger, experimenting, peer pressure, and boredom. Parents on the other hand
      initially cited family historical factors as being a cause for their son's
      firesetting. This study showed the difficulties in attempting to classify
      firesetters. It became clear that there were often multiple motivations involved
      in adolescent firesetting, meanwhile a variation of motivations were reported by
      parents and firesetters. The differences between and ambiguities inherent in
      existing motivational typologies also became evident. The study produced strong
      evidence for the effectiveness of utilising multiple sources to gain a
      comprehensive understanding as to why children deliberately light fires.

PMID- 21948246
TI  - A null mutation of the neuronal sodium channel NaV1.6 disrupts action potential
      propagation and excitation-contraction coupling in the mouse heart.
AB  - Evidence supports the expression of brain-type sodium channels in the heart.
      Their functional role, however, remains controversial. We used global Na(V)1.6
      null mice to test the hypothesis that Na(V)1.6 contributes to the maintenance of
      propagation in the myocardium and to excitation-contraction (EC) coupling. We
      demonstrated expression of transcripts encoding full-length Na(V)1.6 in isolated
      ventricular myocytes and confirmed the striated pattern of Na(V)1.6 fluorescence
      in myocytes. On the ECG, the PR and QRS intervals were prolonged in the null
      mice, and the Ca(2+) transients were longer in the null cells. Under patch
      clamping, at holding potential (HP) = -120 mV, the peak I(Na) was similar in both
      phenotypes. However, at HP = -70 mV, the peak I(Na) was smaller in the nulls. In
      optical mapping, at 4 mM [K(+)](o), 17 null hearts showed slight (7%) reduction
      of ventricular conduction velocity (CV) compared to 16 wild-type hearts. At 12 mM
      [K(+)](o), CV was 25% slower in a subset of 9 null vs. 9 wild-type hearts. These
      results highlight the importance of neuronal sodium channels in the heart,
      whereby Na(V)1.6 participates in EC coupling, and represents an intrinsic
      depolarizing reserve that contributes to excitation.

PMID- 21948249
TI  - Comparing and contrasting the formal and informal crime control views of Indian
      and U.S. College students: a preliminary study.
AB  - This study examined the importance of formal and informal crime control in the
      United States and India. Formal crime control relies on the law and official
      government agencies to deter criminal actions and to respond to criminal
      activity. Informal crime control relies on moral and social institutions (e.g.,
      family, peers, and neighbors) to promote lawful behavior. Using the data
      collected from 928 college students, the study found that the Indian and U.S.
      respondents differed on most of the formal and informal control measures.
      Overall, the Indian respondents were more likely to rank informal control as more
      important than were their U.S. counterparts. Although there were differences,
      both groups of respondents shared similar views on the importance of both forms
      of crime control and held that family was the most important form of crime
      control.

PMID- 21948250
TI  - Human trafficking law and social structures.
AB  - Human trafficking has only recently emerged at the forefront of policy reform,
      even in developed nations. Yet, heightened awareness of the issue has not
      translated into effective policy as the majority of nations have ineffective
      antitrafficking practices; many countries have failed to criminalize human
      trafficking, whereas others do not actively enforce statutes in place. By
      applying Black's theory of law, this study offers a preliminary understanding
      into the variation of global prosecutorial efforts in human trafficking and
      adequacy of antitrafficking law. To isolate this relationship, the effects of
      trafficking markets are controlled. As with prior research, the study finds
      limited support for the theory. The article concludes with a discussion on the
      implications of the quantity of antitrafficking law and morphology association
      for policy development.

PMID- 21948251
TI  - Parole officers' experiences of the symptoms of secondary trauma in the
      supervision of sex offenders.
AB  - The work of parole officers who supervise sex offenders rarely comes to the
      public's attention unless something goes wrong. Research suggests that those
      providing postrelease supervision of convicted sex offenders likely experience
      trauma as a result of their work and that little support is available to respond
      to their emotional needs. This manuscript explores parole officers' and parole
      officer supervisors' experiences of the symptoms of secondary trauma, defined as
      the emotional and cognitive experiences of hearing stories that recount one or
      more traumatic events. The qualitative study described here builds on existing
      literature by providing a detailed exploration, presented in their own words, of
      the experiences of specialist parole officers, about how they cope with the
      symptoms of secondary trauma, and about what they need to help them continue to
      do the job that the public and the politic want done well. Recognizing and
      understanding the symptoms of secondary trauma among supervising officers have
      important implications for maintaining a healthy workforce and for providing
      effective management of sex offenders in the community.

PMID- 21948252
TI  - The roles of social bonds, personality, and perceived costs: an empirical
      investigation into Hirschi's "new" control theory.
AB  - Hirschi's reconceptualized control theory suggests that social bonds serve as the
      primary inhibitors to delinquency and that personality-based self-control (PBSC)
      is not relevant. He also indicates that the number of inhibitors, multiplied by
      their salience, influences the perceived costs of delinquency. These claims have
      not been widely tested. Using a large, school-based sample of adolescents, the
      authors test Hirschi's reconceptualization and find that certain inhibitors
      (e.g., parental monitoring) are more important than others (e.g., maternal
      attachment). There are also unique types of costs (e.g., parental costs, peer
      costs) with differential impacts. Salience exerts a main effect, but there was
      little evidence to suggest it interacts with costs. Finally, PBSC has the
      strongest effect. These findings not only offer support for some of Hirschi's
      claims but also provide directions to better formulate a more comprehensive and
      empirically supported control theory.

PMID- 21948253
TI  - A comparison of rape and molest offenders in prison psychiatric treatment.
AB  - Differences in offense history, brain functioning, and psychological functioning
      of rape (n = 45) and molest offenders (n = 15) who were receiving psychiatric
      treatment while in prison were evaluated. Significant differences were found in
      each of these domains. Rape offenders were more likely to have histories of high
      violence offenses other than sexual offense, including murder, serious juvenile
      offenses, and both juvenile and adult sexual offenses. Rape offenders were more
      likely to show lower intellectual functioning and diffuse brain dysfunction
      associated predominantly with temporal and prefrontal brain cortices. Rape
      offenders were also more likely to display psychological functioning associated
      with illogical thinking and disordered attachment but less immature self-focus
      and fewer feelings of alienation than demonstrated by molest offenders.
      Implications for treatment and social policy for sexual offenders are suggested.
      Logistic regression demonstrated that these neuropsychological measures resulted
      in 71.7% accurate prediction and Rorschach measures resulted in 79.2% accurate
      prediction in differentiating rape from molest offenders. Implications for
      theoretical understanding of sexual offending are discussed.

PMID- 21948254
TI  - Molecular cloning and evolutionary analysis of GJB6 in mammals.
AB  - GJB6 plays a crucial role in hearing. In mammals, bats use ultrasonic
      echolocation for orientation and locating prey. To investigate the evolution of
      GJB6 in mammals, we cloned the full-length coding region of GJB6 from 16 species
      of bats and 4 other mammal species and compared them with orthologous sequences
      in 11 other mammals. The results show purifying selection on GJB6 in mammals, as
      well as in the bat lineage, which indicates an important role for GJB6 in mammal
      hearing. We also found one unique amino acid substitution shared by 16 species of
      bats and 10 shared by two species of artiodactyls. This positioned the
      artiodactyls at an abnormal location in the gene tree. In addition, the
      cytoplasmic loop and carboxy terminus were more variable than other domains in
      all the mammals. These results demonstrate that GJB6 is basically conserved in
      mammals but has undergone relatively rapid evolution in particular lineages and
      domains.

PMID- 21948255
TI  - Integrative data mining to identify novel candidate serum biomarkers for pre
      eclampsia screening.
AB  - OBJECTIVE: Pre-eclampsia (PE) is a serious complication that affects
      approximately 2% of pregnant women worldwide. At present, there is no
      sufficiently reliable test for early detection of PE in a screening setting that
      would allow timely intervention. To help future experimental identification of
      serum biomarkers for early onset PE, we applied a data mining approach to create
      a set of candidate biomarkers. METHODS: We started from the disease etiology,
      which involves impaired trophoblast invasion into the spiral arteries. On the
      basis of this, we used a three-stage filtering strategy consisting of selection
      of tissue-specific genes, textmining for further gene prioritization, and
      identifying blood-detectable markers. RESULTS: This approach resulted in 38
      candidate biomarkers. These include the best three first-trimester serum
      biomarkers for PE found to date LGALS13 (placental protein 13, PP13), PAPPA
      (pregnancy-associated plasma protein-A, PAPP-A), and PGF (placental growth
      factor, PlGF), as well as five proteins previously identified as biomarker after
      the first-trimester or disease onset. This substantiates the effectiveness of our
      approach and provides an important indication that the list will contain several
      new biomarkers for PE. CONCLUSIONS: We anticipate this list can serve in
      prioritization of future experimental studies on serum biomarkers for early onset
      PE.

PMID- 21948256
TI  - Strategies for B-lymphocyte repertoire remodeling in transplantation tolerance.
AB  - Transplantation tolerance remains an elusive goal as B-cell-initiated chronic
      humoral rejection evades current immunosuppression. B-cell-directed therapy is
      thus emerging as a key component in achieving transplantation tolerance and long
      term graft survival. Here, we propose strategies of B-cell repertoire remodeling
      to achieve humoral unresponsiveness to donor antigens with implementation of
      fundamental B-cell immunobiology and use of newly developed B-cell-directed
      agents.

PMID- 21948257
TI  - c-Jun is essential for the induction of Il-1beta gene expression in in vitro
      activated Bergmann glial cells.
AB  - In the central nervous system (CNS), the c-Jun transcription factor has been
      mainly studied in neuronal cells and coupled to apoptotic and regenerative
      pathways following brain injury. Besides, several studies have shown a
      transcriptional role of c-Jun in activated cortical and spinal astrocytes. In
      contrast, little is known about c-Jun expression and transactivation in Bergmann
      glial (BG) cells, the radial cerebellar astrocytes playing crucial roles in
      cerebellar development and physiology. Here, we used neuronal/glial cerebellar
      cultures from neonatal mice to assess putative functions of c-Jun in BG cells. By
      performing double immunocytochemical staining of c-Jun and two BG specific
      markers, S100 and glutamate aspartate transporter (GLAST), we show that c-Jun was
      highly expressed in radial glial cells derived from Bergmann glia. Bergmann glia
      derived cells expressed toll-like receptor 4 and treatment with bacterial
      lipopolysaccharide (LPS)-induced c-Jun phosphorylation at serine 63, a hallmark
      of c-Jun transactivation, exclusively in BG cells. Moreover, LPS-induced IL-1beta
      expression and inhibition of c-Jun N-terminal kinase (JNK) activity abolished
      both c-Jun phosphorylation and the increase of IL-1beta mRNA. Notably, LPS failed
      to induce IL-1beta mRNA in neuronal/glial cerebellar cultures generated from
      conditional knockout mice lacking c-Jun expression in the CNS, indicating the
      essential role of c-Jun in astroglial-specific induction of IL-1beta.
      Immunohistochemical analyses of c-Jun-expressing cells in the early postnatal
      cerebellum confirmed in vivo the expression of c-Jun in BG cells and uncovered a
      dynamic expression of c-Jun during the formation of the BG monolayer. Altogether,
      our finding underlines a putative role of c-Jun in astroglia-mediated
      neuroinflammatory dysfunctions of the cerebellum.

PMID- 21948258
TI  - Association between polymorphisms in the signal transducer and activator of
      transcription and dilated cardiomyopathy in the Chinese Han population.
AB  - The signal transduction pathways mediating the progress of heart failure have
      been intensively studied. Altered signaling of the signal transducers and
      activators of transcription (STATs), which play important roles in regulating
      cell proliferation, differentiation, and apoptosis, has been observed in the
      heart. We conducted a pilot study to test whether single nucleotide polymorphisms
      (SNPs) in STATs were associated with dilated cardiomyopathy (DCM). Genotypes of
      two SNPs of STATs (rs6503691 C/T in exon 1 of STAT5B and rs4796793 C/G in the 5'
      region of STAT3) in 251 DCM patients and 484 control subjects were determined
      with the use of PCR-restriction fragment length polymorphism assay and TaqMan
      assay, respectively. Significantly increased DCM risk was found to be associated
      with T allele of rs6503691 (P = 0.012, OR = 1.37, 95% CI = 1.07-1.74). We found
      that increased DCM risk statistically significantly associated with rs6503691 in
      a dominant model (P = 0.009, OR = 1.50, 95% CI = 1.11-2.04). No association
      between DCM risk and rs4796793 was observed (P = 0.706, OR = 1.05, 95% CI = 0.83
      1.32). The present pilot study provides evidence that both rs6503691 T allele and
      CT/TT genotypes, but not rs4796793 C/G in the 5' region of STAT3, are associated
      with a significantly increased risk of DCM, indicating that common genetic
      polymorphism in STATs is associated with DCM.

PMID- 21948259
TI  - Acute hyperhomocysteinemia alters the coagulation system and oxidative status in
      the blood of rats.
AB  - In the present study, we investigated the effect of the acute administration of
      homocysteine (Hcy) on parameters of the coagulation system, as well as fibrinogen
      and nitrite levels in the blood of rats. In addition, we evaluated the effect of
      acute hyperhomocysteinemia on thiobarbituric acid-reactive substances in plasma
      and on antioxidant enzymes activities (superoxide dismutase, catalase, and
      gluthatione peroxidase) in the erythrocytes of rats. Wistar rats, aged 29 days,
      received a single subcutaneous dorsal injection of saline (control) or Hcy (0.6
      MUmol/g body weight). Fifteen minutes, 1 h, 6 h or 12 h after the injection, the
      rats were euthanized and the blood, plasma, and erythrocytes were collected.
      Results showed that Hcy significantly increased platelet count in the blood and
      plasma fibrinogen levels of rats at 15 min and 1 h, but not at 6 h and 12 h, when
      compared with the control group. Prothrombin time, activated partial
      thromboplastin time, and nitrite levels significantly decreased in plasma at 15
      min and 1 h, but not at 6 h and 12 h after Hcy administration. In addition,
      hyperhomocysteinemia increased thiobarbituric acid-reactive, an index of lipid
      peroxidation, in plasma at 15 min and 1 h; decreased the superoxide dismutase and
      gluthatione peroxidase activity, and increased the catalase activity at 15 min in
      erythrocytes of rats, suggesting that acute Hcy administration may alter the
      oxidative status in the blood of rats. Our findings suggest that
      hypercoagulability and oxidative stress can occur after acute
      hyperhomocysteinemia, possibly in association, at least in part, with the
      vascular dysfunction and thromboembolic complications observed in homocystinuric
      patients.

PMID- 21948260
TI  - Natural vanadium-containing Jeju ground water stimulates glucose uptake through
      the activation of AMP-activated protein kinase in L6 myotubes.
AB  - The aim of this study was to elucidate the effects of natural vanadium-containing
      Jeju ground water on glucose uptake in L6 myotubes and adipogensesis in 3T3 L1
      cells. The Jeju ground water samples containing vanadium components were
      designated as S1 (8.0 +/- 0.9 MUg/l), S2 (24.0 +/- 2.0 MUg/l), and S3 (26.0 +/-
      2.0 MUg/l), respectively. To investigate the effects of the Jeju ground water on
      glucose uptake in L6 myotubes, L6 cells were differentiated in media containing
      deionized distilled water (DDW group) and the water samples (S1, S2, and S3
      groups). After daily changes in cultured media containing the Jeju ground water
      samples for 1 week, all samples had increased glucose uptake compared to the DDW
      group and the order of glucose uptake increased in parallel with vanadium content
      (S3 > S2 > S1). In addition, S3 significantly stimulated the phosphorylation of
      the Thr-172 residue of the AMP-activated protein kinase-alpha subunit and the Ser
      79 subunit of acetyl-CoA carboxylase compared to the DDW group. The effect of
      glucose uptake by S3 was reversed by pretreatment with Compound C, an AMPK
      inhibitor. Interestingly, vanadium pentoxide also increased glucose uptake and
      activated AMPK activity in a dose-dependent manner. Furthermore, as compared to
      the DDW treated group, S3 treatment inhibited adipogenesis of 3T3-L1 cells by
      down regulation of expressions of adipogenic transcription factors. Taken
      together, these findings suggest that S3 displays beneficial effects in the
      treatment of diabetes, at least in part through the activation of AMPK activity.

PMID- 21948261
TI  - Enhanced phosphorylation of caveolar PKC-alpha limits peptide internalization in
      lung endothelial cells.
AB  - We previously reported that the vasoactive peptide 1 (P1, "SSWRRKRKESS")
      modulates the tension of pulmonary artery vessels through caveolar endothelial
      nitric oxide synthase (eNOS) activation in intact lung endothelial cells (ECs).
      Since PKC-alpha is a caveolae resident protein and caveolae play a critical role
      in the peptide internalization process, we determined whether modulation of
      caveolae and/or caveolar PKC-alpha phosphorylation regulates internalization of
      P1 in lung ECs. Cell monolayers were incubated in culture medium containing
      Rhodamine red-labeled P1 (100 MUM) for 0-120 min. Confocal examinations indicate
      that P1 internalization is time-dependent and reaches a plateau at 60 min.
      Caveolae disruption by methyl-beta-cyclodextrin (CD) and filipin (FIL) inhibited
      the internalization of P1 in ECs suggesting that P1 internalizes via caveolae. P1
      stimulation also enhances phosphorylation of caveolar PKC-alpha and increases
      intracellular calcium (Ca(2+)) release in intact cells suggesting that P1
      internalization is regulated by PKC-alpha in ECs. To confirm the roles of
      increased phosphorylation of PKC-alpha and Ca(2+) release in internalization of
      P1, PKC-alpha modulation by phorbol ester (PMA), PKC-alpha knockdown, and Ca(2+)
      scavenger BAPTA-AM model systems were used. PMA-stimulated phosphorylation of
      caveolar PKC-alpha is associated with significant reduction in P1
      internalization. In contrast, PKC-alpha deficiency and reduced phosphorylation of
      PKC-alpha enhanced P1 internalization. P1-mediated increased phosphorylation of
      PKC-alpha appears to be associated with increased intracellular calcium (Ca(2+))
      release since the Ca(2+) scavenger BAPTA-AM enhanced P1 internalization. These
      data indicate that caveolar integrity and P1-mediated increased phosphorylation
      of caveolar PKC-alpha play crucial roles in the regulation of P1 internalization
      in lung ECs.

PMID- 21948262
TI  - Doing science, technology and society in the National Science Foundation :
      commentary on: "Engaged, embedded, enjoined: science and technology studies in
      the National Science Foundation".
AB  - The author describes his efforts to become a participant observer while he was a
      Program Director at the NSF. He describes his plans for keeping track of his
      reflections and his goals before he arrived at NSF, then includes sections from
      his reflective diary and comments after he had completed his two-year rotation.
      The influx of rotators means the NSF has to be an adaptive, learning organization
      but there are bureaucratic obstacles in the way.

PMID- 21948263
TI  - Dissociation of ferritin and hepcidin in a case of adult-onset Still's disease.

PMID- 21948264
TI  - Synergistic effects of combination with fludarabine and carboplatin depend on
      fludarabine-mediated inhibition of enhanced nucleotide excision repair in
      leukemia.
AB  - Overcoming drug resistance remains a major obstacle to curing relapsed or
      refractory lymphoma and obtaining a beneficial long-term prognosis for patients,
      despite the introduction of several salvage regimens to date. Our ultimate
      purpose is to establish a standard second-line salvage chemotherapy regimen for
      curing relapsed/refractory lymphoma. In this basic pre-clinical study, we
      evaluated a combination regimen consisting of 9-beta-D: -arabinofuranosyl-2
      fluoroadenine (F-araA) and carboplatin that targeted nucleotide excision repair
      (NER) of DNA in five representative leukemia lineages in vitro. Isobologram
      analysis demonstrated that simultaneous exposure to these two drugs produced
      synergistic interactions in U937 and K562 cells, in which lines showed enhanced
      NER activity by the measurement of UV or drug-induced DNA strand break (comet
      assay), or quantitation of ERCC1 mRNA (RT-PCR), a key enzyme for NER. Histone
      gammaH2AX formation was synergistically induced, but no such formation was
      observed after exposure to either agent alone in K562 cells. In summary, we
      synergistically inhibited the NER activity of leukemia cells by treating them
      with a combination of F-araA and carboplatin, suggesting that this combinatory
      regimen could be used as a novel salvage therapy for refractory or drug-resistant
      lymphoma.

PMID- 21948265
TI  - Synthesis, crystal structure, Kamlet-Taft and Catalan solvatochromic analysis of
      novel imidazole derivatives.
AB  - Novel imidazole derivatives were synthesized and its crystal structure has been
      studied by single crystal XRD analysis. The photophysical properties of these
      imidazole derivatives were studied in several solvents, which include a wide
      range of apolar, polar and protic media. The observed lower fluorescence quantum
      yield may be due to an increase in the non-radiative deactivation rate constant.
      This is attributed to a loss of planarity in the excited state provided by the
      non co-planarity of the aryl rings attached to C(2) and N(1) atoms of the
      imidazole ring. Such a geometrical change in the excited state leads to an
      important Stokes shift, reducing the reabsorption and reemission effects in the
      detected emission in highly concentrated solutions. The highest fluorescence
      quantum yield of the imidazole derivatives are observed in polar media.

PMID- 21948266
TI  - A modified serial blood sampling technique and utility of dried-blood spot
      technique in estimation of blood concentration: application in mouse
      pharmacokinetics.
AB  - Pharmacokinetic (PK) studies in mice usually require discrete and parallel blood
      sampling owing to a restriction on the volume of blood that can be withdrawn.
      This results in dosing large number of animals and generating composite PK
      profile. To reduce the number of animals and generate individual animal PK
      profiles, we developed a serial sampling technique via tail vein bleeding in
      mice, in which only 20-30 MUL blood was withdrawn per time point. Due to the
      small blood volume, a dried-blood spot (DBS) technique was applied for sample
      processing. The utility of this technique was demonstrated using three test
      compounds (amodiaquine, chloroquine and chlorthalidone), with varying degrees of
      blood-to-plasma partition ratios. The PK studies were carried out in male Balb/c
      mouse weighing 25-30 g. The compounds were administered intravenously via the
      saphenous vein. Blood was collected by composite (retro-orbital plexus) or serial
      (tail vein bleeding) sampling techniques at different time points. Blood samples
      were processed as blood lysate or DBS. Blood or plasma samples were analyzed by
      sensitive and rapid UPLC-MS/MS methods. The blood concentrations (both from blood
      lysate and DBS) obtained from serial sampling matched with those from composite
      sampling. The ratio of blood AUC to plasma AUC correlated well with the in vitro
      blood-to-plasma partition ratio of the compounds. The systemic clearance and
      volume of distribution at steady state calculated from blood or plasma AUCs were
      in proportion to the respective AUCs. Our results indicated that the serial
      sampling technique would reduce the number of animals and also compound usage, as
      well as improve the quality of pharmacokinetic data. Also, the serial sampling
      technique does not require the use of anesthesia and allows estimation of inter
      animal variability in PK. A small volume serial sampling is possible due to the
      availability of the DBS technique.

PMID- 21948267
TI  - Nonalcoholic steatohepatitis (NASH) does not increase complications after
      laparoscopic bariatric surgery.
AB  - BACKGROUND: Advanced liver disease is associated with increased risk for
      postoperative complications. It is not well known whether the presence of
      nonalcoholic steatohepatitis (NASH) in morbidly obese patients contributes to the
      rate of postoperative complications. The main objective was to study the
      association between NASH and postoperative complications in bariatric patients.
      METHODS: A total of 340 contemporary sequential patients who underwent
      laparoscopic bariatric operations and who had intraoperative liver biopsies were
      studied. The rates of severe postoperative complications were compared across
      three patient groups-those with (1) no liver disease or with simple steatosis,
      (2) mild nonalcoholic NASH [steatosis with necroinflammation and mild fibrosis
      (stage 0-1)], and (3) advanced NASH [steatosis, necroinflammation, and more
      advanced fibrosis (stage >= 2)]. RESULTS: Of 340 patients, 141 (42%) had no NASH,
      and 151 (44%) and 48 (14%) had mild and advanced NASH, respectively. Superobesity
      (P = 0.037), diabetes (P < 0.001), and cerebrovascular disease (P = 0.013) had
      highest frequencies in patients with advanced NASH. Hypertension was highly
      prevalent in cohort (57%) but similarly distributed across three groups. Forty
      five patients experienced at least one complication (pulmonary 4, cardiovascular
      8, surgical 16, and acute kidney injury 21). The complications rate did not
      differ significantly across NASH categories. Median hospital stay was 3 days (IQR
      2, 3), and it was not associated with NASH severity. There were no 30-day
      postoperative deaths. CONCLUSIONS: Despite the high prevalence of NASH among
      morbidly obese surgical patients, this condition was not associated with
      increased risk for postoperative complications. Postoperative acute kidney injury
      was the most frequent single complications.

PMID- 21948269
TI  - Identification of single nucleotide polymorphisms in the Nicastrese goat and
      Sardinia sheep mannose-binding lectin.
AB  - This study was undertaken to detect polymorphisms in the goat and sheep mannose
      binding lectin encoding gene (MBL2) and to explore allelic variability of this
      gene in these two species. The analysis and comparison of the sequences obtained
      from sheep showed 13 polymorphic sites, six in the promoter and seven in exon 1,
      four of which were of the missense type. In the goats, 12 polymorphic sites were
      detected, five intronic, five in the promoter, and one exonic. The exon site was
      responsible for an amino acid change. Mutations detected at the MBL2 locus in the
      sheep are of particular interest, being potentially responsible for the
      alterations of gene expression. A population survey involved 102 ewes of the
      Sardinian breed and 218 goats of the Nicastrese breed, all reared in southern
      Italy.

PMID- 21948268
TI  - Developmental expression of plasma glutathione peroxidase during mouse
      organogenesis.
AB  - Plasma glutathione peroxidase (pGPx) is an extracellular antioxidative
      selenoenzyme which has been detected in various adult tissues, but little is
      known about the expression and distribution of pGPx during embryogenesis. To
      investigate the expression patterns of pGPx during embryogenesis, we performed
      quantitative real-time PCR, in situ hybridization, Western blot, and
      immunohistochemistry analyses in whole embryos or each developing organ of mice
      on embryonic days (E)7.5-18.5. In whole embryos of E7.5-8.5, pGPx mRNA was more
      typically expressed in extra-embryonic tissues including ectoplacental cone,
      trophectoderm, and decidual cells than in embryos. However, after E9.5, pGPx mRNA
      and protein levels were increased in the embryos with differentiation and growth,
      but trended to gradually decrease in the extra-embryonic tissues until E18.5. In
      sectioned embryonic tissues on E13.5-18.5, pGPx mRNA and protein were mainly
      expressed in the developing nervous tissues, the sensory organs, and the
      epithelia of lung, skin, and intestine, the heart and artery, and the kidney. In
      particular, pGPx immunoreactivity was very strong in the developing liver. These
      results indicate that pGPx is spatio-temporally expressed in various embryonic
      organs as well as extra-embryonic tissues, suggesting that pGPx may function to
      protect the embryos against endogenous and exogenous reactive oxygen species
      during organogenesis.

PMID- 21948271
TI  - Synchronous Hepatocellular Carcinoma and Gastric Carcinoma-A Case Report with
      Review of the Literature.

PMID- 21948270
TI  - Portal vein embolisation for extended hepatectomy: single-centre experience.
AB  - BACKGROUND: Portal vein embolisation (PVE) induces contra-lateral liver
      hypertrophy to facilitate an extended hepatectomy. AIM: This paper aims to
      analyse our data on PVE and extended hepatectomy. Outcome measures included
      success of PVE, feasibility of resections, operative morbidity and survival.
      METHODS: A retrospective analysis of data collected prospectively on 33 patients
      (2004-2008) was performed. Survival curves were estimated by the Kaplan-Meier
      (Breslow) method. Significance was defined as p < 0.05. RESULTS: A total of 31
      patients had successful PVE. There were 24 patients who underwent surgery.
      Significant hypertrophy of residual liver was noted from 230.15 (pre
      embolisation) to 428.50 ml (post-embolisation) (median, p < 0.0001). A total of
      16 patients had hepatectomy (14: R0; 2: R1) with a single mortality (6.25%) and
      56.25% morbidity, and a median length of stay of 17 days. Median overall survival
      was 14 (95% CI 7.8-20.2) months. Patients who underwent resection had a median
      disease-specific survival of 33 (95% CI 4-62) months compared with 8.6 (95% CI 0
      19.9) months for patients without resection (p = 0.14). For patients with primary
      hepato-biliary tumours, the median disease-specific survival was 7.9 (95% CI 4.5
      11.3) months compared with a median survival of 19.7 (95% CI 0-42.2) months for
      patients with metastases (p = 0.07). CONCLUSIONS: PVE is safe, facilitates R0
      resection and offers the best chance of cure, especially for liver metastases.

PMID- 21948272
TI  - Reactive oxygen species mediated tissue damage in high energy proton irradiated
      mouse brain.
AB  - Although radiation related research has been conducted extensively, the molecular
      toxicology and cellular mechanisms affected by proton radiation remain poorly
      understood. We recently reported that the high energy protons induce cell death
      through activation of apoptotic signaling genes; caspase 3 and 8 (Baluchamy et
      al. J Biol Chem 285:24769-24774, 2010). In this study, we investigated the effect
      of different doses of protons in in vivo mouse system, particularly, brain
      tissues. A significant dose-dependent induction of reactive oxygen species and
      lipid peroxidation and reduction of antioxidants; glutathione and superoxide
      dismutase were observed in proton irradiated mouse brain as compared to control
      brain. Furthermore, histopathology studies on proton irradiated mouse brain
      showed significant tissue damage as compared to control brain. Together, our in
      vitro and in vivo results suggest that proton irradiation alters oxidant and
      antioxidant levels in the cells to cause proton mediated DNA/tissue damage
      followed by apoptotic cell death.

PMID- 21948275
TI  - Fluid loading for cesarean delivery under spinal anesthesia: have we studied all
      the options?

PMID- 21948273
TI  - Extracellular 14-3-3 from human lung epithelial cells enhances MMP-1 expression.
AB  - Airway remodelling in asthma involves various mediators modulating the
      production/breakdown of collagen by lung fibroblasts. Matrix metalloproteinase-1
      (MMP-1) plays an important role in collagen breakdown. We recently showed that
      epithelial cell-derived extracellular form of 14-3-3sigma is an important inducer
      of MMP-1 expression in skin fibroblasts. Thus, we hypothesized that 14-3-3
      proteins are important regulators of MMP-1 expression in the respiratory airway.
      We examined the presence of extracellular 14-3-3 proteins in conditioned media
      obtained from primary lung epithelial cells, A549 and HS24 cells, and their
      effect on MMP-1 expression by lung fibroblasts (IMR-90). In addition, we
      evaluated IMR-90 response to 14-3-3 proteins in the presence of transforming
      growth factor-beta(1) (TGF-beta(1)), a cytokine known to decrease MMP-1
      expression by fibroblasts. Extracellular 14-3-3alpha/beta, but not -sigma, is
      released by the human-derived lung epithelial cell lines, A549 and HS24. Unlike
      dermal fibroblasts, IMR-90 cells do not produce MMP-1 in response to 14-3-3sigma.
      Conversely, MMP-1 production was induced following treatment of IMR-90 with
      recombinant or lung epithelial cell-derived 14-3-3alpha/beta. These findings were
      also confirmed using primary human bronchial epithelial cells and lung
      fibroblasts obtained from non-asthmatic patients. The MMP-1-inducing effect of 14
      3-3alpha/beta on IMR-90 was not inhibited by TGF-beta(1). Lung epithelial cell
      derived 14-3-3alpha/beta has a potent MMP-1-inducing effect on airway
      fibroblasts. Modulation of MMP-1 by 14-3-3alpha/beta, may be important in the
      alteration of collagenase production associated with airway remodelling in
      obstructive lung diseases. Our data indicate that 14-3-3 proteins may be
      potential targets for future therapeutic strategies aimed at modulating tissue
      remodelling in asthma.

PMID- 21948276
TI  - The importance of being negative.

PMID- 21948277
TI  - Local infiltration analgesia for pain after total knee replacement surgery: a
      winner or just a strong runner-up?

PMID- 21948278
TI  - Tripping over perineural catheters.

PMID- 21948279
TI  - Ultrasound-guided infraclavicular block: to target the axillary artery or the
      cords?

PMID- 21948280
TI  - High frequency ventilation and atrial fibrillation ablation.

PMID- 21948281
TI  - Use of a modified Ovassapian airway to increase mouth opening for fiberoptic
      orotracheal intubation in a patient with severe trismus.

PMID- 21948282
TI  - Inhibitory effect of 10-hydroxy-trans-2-decenoic acid on LPS-induced IL-6
      production via reducing IkappaB-zeta expression.
AB  - The effect of 10-hydroxy-trans-2-decenoic acid (10H2DA), a major fatty acid
      component of royal jelly, was investigated on LPS-induced cytokine production in
      murine macrophage cell line, RAW264 cells. 10H2DA inhibited LPS-induced IL-6
      production dose-dependently, but did not inhibit TNF-alpha production. 10H2DA
      inhibited LPS-induced NF-kappaB activation in a dose-dependent fashion. In
      addition, NF-kappaB activation induced by over-expression of either MyD88 or
      Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF) was also
      inhibited by 10H2DA. Degradation of IkappaB-alpha and phosphorylation of IkappaB
      kinase-alpha were not inhibited by 10H2DA. On the other hand, reduction of LPS
      induced IkappaB-zeta expression was discovered. Production of lipocalin-2 and
      granulocyte colony-stimulating factor (G-CSF), which is dependent on IkappaB
      zeta, was also inhibited by 10H2DA, whereas that of IkappaB-zeta-independent
      cytokines/chemokines, such as IFN-beta, murine monocyte chemotactic protein-1
      (JE), macrophage inflammatory protein (MIP)-1alpha and MIP-2, was not. Together,
      10H2DA specifically inhibited LPS-induced IkappaB-zeta expression, followed by
      inhibition of IkappaB-zeta-dependent gene production. These results suggest that
      10H2DA is one of the components of royal jelly to show anti-inflammatory effects
      and could be a therapeutic drug candidate for inflammatory and autoimmune
      diseases associated with IkappaB-zeta and IL-6 production.

PMID- 21948284
TI  - An experimental investigation of verbal expression of emotion in anorexia and
      bulimia nervosa.
AB  - OBJECTIVE: This study aims to use an experimental design to investigate verbal
      expression of emotion in anorexia nervosa (AN) and bulimia nervosa (BN). METHOD:
      Forty-two patients with AN, 26 patients with BN and 34 healthy controls (HCs)
      were videoed talking about discrete emotional experiences. Talks were analysed
      using the Linguistic Inquiry and Word Count. Participants also completed the
      Emotion Regulation Questionnaire (ERQ). RESULTS: People with AN used fewer words
      when describing their emotional experiences and fewer positive affect words than
      HCs. People with BN were indistinguishable from HCs. Both ED groups had higher
      scores on the suppression subscale of the ERQ compared with HCs. Suppression was
      negatively correlated with negative verbal expression. DISCUSSION: This study
      highlights differences between AN and BN in emotion expression. It supports a
      model of AN, which highlights emotion inhibition as a maintaining factor of the
      illness. Methods of emotion regulation in EDs may contribute to increased
      negative mood and poorer social functioning.

PMID- 21948285
TI  - Coherence masking protection for speech in children and adults.
AB  - In three experiments, we tested the hypothesis that children are more obliged
      than adults to fuse components of speech signals and asked whether the principle
      of harmonicity could explain the effect or whether it is, instead, due to
      children's implementing speech-based mechanisms. Coherence masking protection
      (CMP) was used, which involves labeling a phonetically relevant formant (the
      target) presented in noise, either alone or in combination with a stable spectral
      band (the cosignal) that provides no additional information about phonetic
      identity and is well outside the critical band of the target. Adults and children
      (8 and 5 years old) heard stimuli that were either synthetic speech or hybrids
      consisting of sine wave targets and synthetic cosignals. The target and cosignal
      either shared a common harmonic structure or did not. An adaptive procedure
      located listeners' thresholds for accurate labeling. Lower thresholds when the
      cosignal is present indicate CMP. Younger children demonstrated CMP effects that
      were both larger in magnitude and less susceptible to disruptions in harmonicity
      than those observed for adults. The conclusion was that children are obliged to
      integrate spectral components of speech signals, a perceptual strategy based on
      their recognition of when all components come from the same generator.

PMID- 21948283
TI  - The QKI-PLP pathway controls SIRT2 abundance in CNS myelin.
AB  - Sirtuin 2 (SIRT2), a nicotinamide adenine dinucleotide (NAD)-dependent
      deacetylase expressed by oligodendrocytes (OLs), the myelin-producing cells of
      the central nervous system (CNS), is markedly up-regulated during active
      myelination (Li et al. (2007) J Neurosci 27:2606-2616; Southwood et al. (2007)
      Neurochem Res 32:187-195; Werner et al. (2007) J Neurosci 27:7717-7730). SIRT2 is
      a component of the myelin proteome and is severely reduced in the Plp1 knockout
      mouse brain, in which both proteolipid protein (PLP) and DM20 are absent (Werner
      et al. (2007) J Neurosci 27:7717-7730). The mechanisms that regulate SIRT2
      expression in OLs and myelin remain to be investigated. We report for the first
      time that the expression of SIRT2 is regulated by the QKI-dependent pathway and
      this effect is mediated through selective regulation of PLP. In the homozygous
      quakingviable (qk(v) /qk(v) ) mutant mouse that harbors QKI deficiency in OLs
      (Bockbrader and Feng (2008) Future Neurol 3:655-668; Ebersole et al. (1996) Nat
      Genet 12:260-265; Hardy et al. (1996) J Neurosci 16:7941-7949), PLP, but not DM20
      mRNA, was selectively down-regulated and SIRT2 protein was severely reduced
      whereas SIRT2 mRNA expression was unaffected. Expression of the cytoplasmic
      isoform QKI6 in OLs (Zhao et al. (2006) J Neurosci 26:11278-11286) rescued SIRT2
      expression in the qk(v) /qk(v) mutant concomitantly with restoration of PLP
      expression. Moreover, SIRT2 protein is diminished in myelin tracts and compact
      myelin of the PLP-ISEdel mutant brain, in which PLP protein but not DM20 is
      selectively reduced (Wang et al. (2008) Exp Neurol 214:322-330). In contrast,
      SIRT2 expression and its cellular function in regulating process complexity are
      not affected by the absence of PLP in PLP-ISEdel non-myelinating OLs.
      Collectively, our results indicate that the abundance of SIRT2 in myelin is
      dependent on PLP, but not DM20.

PMID- 21948286
TI  - Detection of porcine circovirus type 1 in commercial porcine vaccines by loop
      mediated isothermal amplification.
AB  - A loop-mediated isothermal amplification (LAMP) method with a real-time
      monitoring system was developed for the detection of porcine circovirus type 1
      (PCV1) in commercial swine vaccines. This method was highly specific for PCV1. No
      cross-reaction to porcine circovirus type 2, porcine parvovirus, pseudorabies
      virus, classical swine fever virus, and porcine reproductive and respiratory
      syndrome virus was observed. The analytical sensitivity of the LAMP for PCV1 DNA
      was 10 copies/MUl in the case of positive recombinant plasmid comparable to that
      obtained from the nested polymerase chain reaction (nested PCR). Furthermore, 25
      commercial swine vaccines were tested by both the LAMP and the nested PCR, and
      three of them were tested positive for PCV1 DNA. These results indicate that PCV1
      DNA can be real-time detected by the LAMP; the method was highly specific,
      sensitive, and rapid for the detection of PCV1 DNA, particularly in commercial
      swine vaccines.

PMID- 21948287
TI  - Complications of the lateral transpsoas approach for lumbar interbody
      arthrodesis: a case series and literature review.
AB  - BACKGROUND: The lateral transpsoas approach to the lumbar spine was developed to
      eliminate the need for an anterior-approach surgeon and retraction of the great
      vessels and has the potential for shorter operative times. However, the reported
      complications associated with this approach vary. QUESTIONS/PURPOSES: We
      identified the incidence of complications associated with the lateral transpsoas
      approach to the lumbar spine. PATIENTS AND METHODS: We retrospectively reviewed
      45 patients who underwent a lateral transpsoas approach to the spine for various
      diagnoses between January 1, 2006, and October 31, 2010. The patients' average
      age was 63.3 years. Sixteen (35.6%) patients had prior lumbar spinal surgery.
      Twenty-one patients (46.7%) underwent supplemental posterior instrumentation.
      Minimum followup was 0 months (mean, 11 months; range, 0-34 months). RESULTS:
      Eighteen of the 45 patients (40%) had complications: 10 (22.2%) developed
      postoperative iliopsoas weakness, three had quadriceps weakness, and one
      experienced foot drop. Eight patients (17.8%) developed anterior thigh
      hypoesthesia, which did not fully resolve in seven of the eight patients at an
      average of 9 months' followup. Three patients had postoperative radiculopathies,
      one a durotomy, and one died postoperatively from a pulmonary embolism.
      CONCLUSIONS: We found a 40% incidence of complications and a nontrivial frequency
      and severity of postoperative weakness, numbness, and radicular pain in patients
      who underwent a lateral transpsoas approach to the spine. Given the expanding use
      of the approach, a thorough understanding of the risks associated with it is
      essential for patient education, medical decision making, and identifying methods
      of reducing such complications. LEVEL OF EVIDENCE: Level IV, therapeutic study.
      See Guidelines for Authors for a complete description of levels of evidence.

PMID- 21948288
TI  - Minimizing dynamic knee spacer complications in infected revision arthroplasty.
AB  - BACKGROUND: Deep infections are devastating complications of TKA often treated
      with component explantation, intravenous antibiotics, and antibiotic-impregnated
      cement spacers. Historically, the spacers have been static, which may limit
      patients' ROM and ability to walk. Several recent reports describe dynamic
      spacers, which may allow for improved ROM and make later reimplantation easier.
      However, because of several dynamic spacer problems noted at our institution, we
      wanted to assess their associated failures, reinfection rates, and functionality.
      QUESTIONS/PURPOSES: We therefore asked whether there were differences between
      static and dynamic spacers in (1) reinfection rates, (2) complications directly
      related to the spacer, and (3) final patient functionality as measured by Knee
      Society objective scores and ROM. PATIENTS AND METHODS: We retrospectively
      identified 111 patients (115 knees) with 34 dynamic spacers (30%) and 81 static
      spacers (70%). Reinfection rates, complications requiring additional surgery, and
      final Knee Society scores and ROM were collected for all patients. RESULTS:
      Reinfection rates were comparable between groups. In the dynamic spacer cohort,
      there were four complications; however, these could all be explained by surgical
      technical errors or patient weightbearing compliance. All patients with failed
      results eventually underwent successful two-stage exchange arthroplasty. Final
      Knee Society scores and ROM were also similar between groups. CONCLUSIONS:
      Reinfection rates, Knee Society scores, and ROM were comparable between the
      static and dynamic spacer groups. Meticulous surgical technique and proper
      patient selection should be used to avoid any complications with any spacers.

PMID- 21948289
TI  - Is there a dynamic protein contribution to the substrate trigger in coenzyme B12
      dependent ethanolamine ammonia lyase?

PMID- 21948290
TI  - Copeptin adds to high-sensitivity troponin T in rapid rule out of acute
      myocardial infarction.

PMID- 21948291
TI  - Comparison of midregional pro-A-type natriuretic peptide and the N-terminal pro-B
      type natriuretic peptide for predicting mortality and cardiovascular events.
AB  - BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) provides
      prognostic information on mortality and future cardiovascular events for
      individuals from the general population. A novel immunoassay was recently
      developed that measures a midregional fragment of pro-A-type natriuretic peptide
      (MR-proANP). We compared the capabilities of MR-proANP and NT-proBNP for
      predicting mortality and cardiovascular events in a population-based study.
      METHODS: A total of 7819 patients participated in the population-based Prevention
      of Renal and Vascular End-stage Disease (PREVEND) study, a prospective
      observational study. Three clinical end points were studied: all-cause mortality,
      cardiovascular mortality, and cardiovascular events. After a median follow-up of
      10.5 years, we used a Cox proportional hazards model to investigate the
      relationship between the 2 natriuretic peptides and the clinical end points. The
      Harrell C statistic and the integrated discrimination improvement (IDI) were used
      to compare MR-proANP and NT-proBNP. RESULTS: Increased plasma concentrations of
      both natriuretic peptides were associated with an increased risk of all-cause
      mortality and cardiovascular events, after adjustment for age, sex, and other
      cardiovascular risk factors. According to the Harrell C statistic analysis, the
      models with MR-proANP and NT-proBNP were comparable in predicting all-cause
      mortality, cardiovascular mortality, and cardiovascular events. In contrast to NT
      proBNP, MR-proANP was not independently related to cardiovascular mortality. In
      all models, the IDI was higher for NT-proBNP than for MR-proANP. CONCLUSIONS: MR
      proANP was as efficient as NT-proBNP in predicting all-cause mortality,
      cardiovascular mortality, and cardiovascular events; however, its association
      with cardiovascular mortality was not independent from other confounders.

PMID- 21948292
TI  - Copeptin--a novel marker in acute myocardial infarction.

PMID- 21948293
TI  - Vitamin d receptor gene variants and esophageal adenocarcinoma risk: a population
      based case-control study.
AB  - PURPOSE: Polymorphisms in the vitamin D receptor (VDR) gene may be of etiological
      importance in determining cancer risk. The aim of this study was to assess the
      association between common VDR gene polymorphisms and esophageal adenocarcinoma
      (EAC) risk in an all-Ireland population-based case-control study. METHODS: EAC
      cases and frequency-matched controls by age and gender recruited between March
      2002 and December 2004 throughout Ireland were included. Participants were
      interviewed, and a blood sample collected for DNA extraction. Twenty-seven single
      nucleotide polymorphisms in the VDR gene were genotyped using Sequenom or TaqMan
      assays while the poly(A) microsatellite was genotyped by fluorescent fragment
      analysis. Unconditional logistic regression was applied to assess the association
      between VDR polymorphisms and EAC risk. RESULTS: A total of 224 cases of EAC and
      256 controls were involved in analyses. After adjustment for potential
      confounders, TT homozygotes at rs2238139 and rs2107301 had significantly reduced
      risks of EAC compared with CC homozygotes. In contrast, SS alleles of the poly(A)
      microsatellite had significantly elevated risks of EAC compared with SL/LL
      alleles. However, following permutation analyses to adjust for multiple
      comparisons, no significant associations were observed between any VDR gene
      polymorphism and EAC risk. CONCLUSIONS: VDR gene polymorphisms were not
      significantly associated with EAC development in this Irish population.
      Confirmation is required from larger studies.

PMID- 21948294
TI  - Colorectal Carcinoma Masquerading Empyema of the Gallbladder: A Case Report with
      Literature Review.

PMID- 21948295
TI  - Influence of dentin substrates to simplify wet-bonding: a leakage-free and
      reliable tensile strength interface for long-lasting restorations.
AB  - The wet-bonding procedure can be simplified by eliminating the primer. An aqueous
      mixture of 1% citric acid and 1% ferric chloride (1-1) was hypothesized as
      providing an easier dehydratable thinner substrate to which 4-META/MMA-TBB resin
      can adhere reliably. The 1-1 was applied for 10 s and rinsed off with water for
      10 s. Demineralized dentin under four conditions was prepared before bonding to
      PMMA rod using 4-META/MMA-TBB resin: air-dried 10 s (D-NP); air-dried 10 s,
      primed 60 s with 5% 4-META in acetone (D-P); blotted dry 10 s (W-NP); blotted dry
      10 s, primed 60 s (W-P). The tensile strengths (MPa) using mini-dumbbell
      specimens were 4.0 +/- 2.4 for D-NP, 10.6 +/- 5.4 for D-P, 38.3 +/- 4.4 for W-NP,
      and 42.9 +/- 3.3 for W-P. There was no significant difference between W-NP and W
      P with cohesive failure in the dentin and the cured resin. In the wet groups, the
      hybridized dentin was stable against both HCl and NaOCl challenges. TEM
      examination and a leakage tests confirmed a perfect seal with a leakage-free
      interface of W-NP. These results suggest that this primer-less wet-bonding is
      promising method to protect the underlying intact dentin and pulp, thus providing
      long-lasting dental treatment.

PMID- 21948296
TI  - Alemtuzumab therapy in T-cell prolymphocytic leukemia: comparing efficacy in a
      series treated intravenously and a study piloting the subcutaneous route.
AB  - Intravenous alemtuzumab is an effective and well-tolerated treatment for T-cell
      prolymphocytic leukemia (T-PLL). Alemtuzumab given intravenously as first-line
      treatment in 32 patients resulted in an overall response rate of 91% with 81%
      complete responses. Studies in B-cell chronic lymphocytic leukemia have shown
      subcutaneous alemtuzumab to be equally as effective as intravenous alemtuzumab.
      The UKCLL05 pilot study examined the efficacy and toxicity of this more
      convenient method of administration in 9 previously untreated patients with T
      PLL. Only 3 of 9 patients (33%) responded to treatment. Furthermore, 2 of 9
      patients (22%) died while on treatment. Recruitment was terminated because of
      these poor results. After rescue therapy with intravenous alemtuzumab and/or
      pentostatin, median progression-free survival and overall survival were similar
      to the intravenous group. Alemtuzumab delivered intravenously, but not
      subcutaneously, remains the treatment of choice for previously untreated T-PLL.

PMID- 21948297
TI  - CD40 stimulation sensitizes CLL cells to lysosomal cell death induction by type
      II anti-CD20 mAb GA101.
AB  - Sensitivity of chronic lymphocytic leukemia (CLL) cells to anti-CD20 mAbs is low
      and, therefore, the efficacy of monotherapy with current anti-CD20 mAbs is
      limited. At present, it is not known whether sensitivity of CLL cells to CD20
      mAbs is modulated by microenvironmental stimuli. We have shown previously that in
      vitro CD40 stimulation of peripheral blood-derived CLL cells results in
      resistance to cytotoxic drugs. In the present study, we show that, in contrast,
      CD40 stimulation sensitizes CLL cells to the recently described novel type II
      anti-CD20 mAb GA101. Cell death occurred without cross-linking of GA101 and
      involved a lysosome-dependent mechanism. Combining GA101 with various cytotoxic
      drugs resulted in additive cell death, not only in CD40-stimulated CLL cells, but
      also in p53-dysfunctional CLL cells. Our findings indicate that GA101 has
      efficacy against chemoresistant CLL, and provide a rationale for combining
      cytotoxic drugs with anti-CD20 mAbs.

PMID- 21948298
TI  - Second induction with high-dose cytarabine and mitoxantrone: different impact on
      pediatric AML patients with t(8;21) and with inv(16).
AB  - Patients with core binding factor acute myeloid leukemia (CBF-AML) benefit from
      more intensive chemotherapy, but whether both the t(8;21) and inv(16)/t (16;16)
      subtypes requires intensification remained to be determined. In the 2 successive
      studies (AML-BFM-1998 and AML-BFM-2004), 220 CBF-AML patients were treated using
      the same chemotherapy backbone, whereby reinduction with high-dose cytarabine and
      mitoxantrone (HAM) was scheduled for these cohorts only in study AML-BFM-1998 but
      not in AML-BFM-2004 against the background to minimize overtreatment. Five-year
      overall survival (OS) and event-free survival (EFS) were significantly higher and
      the cumulative incidence of relapse (CIR) lower in t(8;21) patients treated with
      HAM (n = 78) compared with without HAM (n = 53): OS 92% +/- 3% versus 80% +/- 6%,
      p(logrank)0.047, EFS 84% +/- 4% versus 59% +/- 7%, p(logrank)0.001, and CIR 14%
      +/- 4% versus 34% +/- 7%, p((gray))0.006. These differences were not seen for
      inv(16) (n = 43 and 46, respectively): OS 93% +/- 4% versus 94% +/- 4%, EFS 75%
      +/- 7% versus 71% +/- 9% and CIR 15% +/- 6% versus 23% +/- 8% (not significant).
      The subtype t(8;21), but not inv(16), was an independent predictor of worse
      outcome without HAM reinduction. Based on our data, a 5-year OS of > 90% can be
      expected for CBF-AML, when stratifying t(8;21), but not inv(16), patients to high
      risk chemotherapy, including HAM reinduction.

PMID- 21948300
TI  - Preemptive immunotherapy in childhood acute myeloid leukemia for patients showing
      evidence of mixed chimerism after allogeneic stem cell transplantation.
AB  - Previous studies have shown that children with acute myeloid leukemia (AML) who
      developed mixed chimerism (MC) were at high risk for relapse after allogeneic
      stem-cell transplantation (allo-SCT). We investigated the feasibility of
      intensified preemptive immunotherapy in children receiving allo-SCT for AML.
      Eighty-four children were registered in our trial from May 2005 to April 2009; of
      these, 71 fulfilled the inclusion criteria and were treated according to the
      study protocol. Serial and semiquantitative analyses of posttransplantation
      chimerism were performed. Defined immunotherapy approaches were considered in MC
      patients. Continuous complete chimerism (CC) was observed in 51 of 71 patients.
      MC was detected in 20 patients and was followed by immunotherapy in 13. Six of 13
      MC patients returned to CC without toxicity and remained in long-term remission.
      Overall, the probability of event-free survival (pEFS) was 66% (95% confidence
      interval [95% CI] = 53%-76%) for all patients and 46% (95% CI = 19%-70%) in MC
      patients with intervention; however, this number increased to 71% (95% CI = 26%
      92%) in 7 of 13 MC patients on immunotherapy who were in remission at the time of
      transplantation. All MC patients without intervention relapsed. These results
      suggest that MC is a prognostic factor for impending relapse in childhood AML,
      and that preemptive immunotherapy may improve the outcome in defined high-risk
      patients after transplantation.

PMID- 21948299
TI  - NUP98 gene fusions and hematopoietic malignancies: common themes and new biologic
      insights.
AB  - Structural chromosomal rearrangements of the Nucleoporin 98 gene (NUP98),
      primarily balanced translocations and inversions, are associated with a wide
      array of hematopoietic malignancies. NUP98 is known to be fused to at least 28
      different partner genes in patients with hematopoietic malignancies, including
      acute myeloid leukemia, chronic myeloid leukemia in blast crisis, myelodysplastic
      syndrome, acute lymphoblastic leukemia, and bilineage/biphenotypic leukemia.
      NUP98 gene fusions typically encode a fusion protein that retains the amino
      terminus of NUP98; in this context, it is important to note that several recent
      studies have demonstrated that the amino-terminal portion of NUP98 exhibits
      transcription activation potential. Approximately half of the NUP98 fusion
      partners encode homeodomain proteins, and at least 5 NUP98 fusions involve known
      histone-modifying genes. Several of the NUP98 fusions, including NUP98-homeobox
      (HOX)A9, NUP98-HOXD13, and NUP98-JARID1A, have been used to generate animal
      models of both lymphoid and myeloid malignancy; these models typically up
      regulate HOXA cluster genes, including HOXA5, HOXA7, HOXA9, and HOXA10. In
      addition, several of the NUP98 fusion proteins have been shown to inhibit
      differentiation of hematopoietic precursors and to increase self-renewal of
      hematopoietic stem or progenitor cells, providing a potential mechanism for
      malignant transformation.

PMID- 21948301
TI  - Novel treatment concepts for graft-versus-host disease.
AB  - Acute and chronic graft-versus-host disease (GVHD) are potentially lethal
      complications after stem cell transplantation (SCT). Steroids are the appropriate
      first-line treatment for both. However, if patients do not adequately benefit
      from steroid therapy, mortality is high and standardized treatment algorithms are
      lacking. This is mainly because of limited data from prospective, randomized
      clinical trials. In addition, most of the available treatment options only induce
      clinical benefits in a limited proportion of patients. Thus, there is an urgent
      clinical need to develop more potent immunosuppressive treatment strategies for
      patients suffering from acute or chronic steroid-refractory GVHD while
      maintaining the graft versus tumor effect to avoid a potential rise in relapse
      related mortality. The increasing knowledge about host- as well as donor-derived
      variables favoring GVHD development and the increasing armamentarium of immune
      modulatory agents entering preclinical and clinical research will probably allow
      more effective treatment of GVHD in the future. This review describes novel
      developments in the treatment of steroid-refractory GVHD, with a special focus on
      the rationale behind promising pharmacologic compounds or up-coming cellular
      therapies.

PMID- 21948302
TI  - Application of quality by design principles to the development and technology
      transfer of a major process improvement for the manufacture of a recombinant
      protein.
AB  - This study describes the application of quality by design (QbD) principles to the
      development and implementation of a major manufacturing process improvement for a
      commercially distributed therapeutic protein produced in Chinese hamster ovary
      cell culture. The intent of this article is to focus on QbD concepts, and provide
      guidance and understanding on how the various components combine together to
      deliver a robust process in keeping with the principles of QbD. A fed-batch
      production culture and a virus inactivation step are described as representative
      examples of upstream and downstream unit operations that were characterized. A
      systematic approach incorporating QbD principles was applied to both unit
      operations, involving risk assessment of potential process failure points, small
      scale model qualification, design and execution of experiments, definition of
      operating parameter ranges and process validation acceptance criteria followed by
      manufacturing-scale implementation and process validation. Statistical
      experimental designs were applied to the execution of process characterization
      studies evaluating the impact of operating parameters on product quality
      attributes and process performance parameters. Data from process characterization
      experiments were used to define the proven acceptable range and classification of
      operating parameters for each unit operation. Analysis of variance and Monte
      Carlo simulation methods were used to assess the appropriateness of process
      design spaces. Successful implementation and validation of the process in the
      manufacturing facility and the subsequent manufacture of hundreds of batches of
      this therapeutic protein verifies the approaches taken as a suitable model for
      the development, scale-up and operation of any biopharmaceutical manufacturing
      process.

PMID- 21948303
TI  - Apolipoprotein A-I peptide models as probes to formulate potential inhibitors of
      the low-density lipoprotein oxidation.
AB  - Apolipoprotein A-I (apoA-I), which constitutes the principal protein component of
      high-density lipoprotein, is responsible for its major antiatherogenic functions.
      Aiming at contributing to the development of potent inhibitors of low-density
      lipoprotein (LDL) peptide models of helices 4,6 and 9,10 of apoA-I were designed
      and synthesized. Specific amino acid substitutions, resulting in transformation
      of the original helix class A and Y to G according to the Schiffer and Edmundson
      helical wheel representation, were introduced in order to validate the
      contribution of these modifications in the inhibitory activity of the synthesized
      peptide models against the LDL oxidation. The role of Met at positions 112 (helix
      4) and 148 (helix 6) as oxidant scavenger was also investigated. The helical
      characteristics of all the peptide models were studied by CD in membrane
      mimicking microenvironments and compared with the original helices.

PMID- 21948304
TI  - A chitin nanofiber ink for airbrushing, replica molding, and microcontact
      printing of self-assembled macro-, micro-, and nanostructures.

PMID- 21948305
TI  - Temporal memory of emotional experience.
AB  - The few studies that have investigated judgments of time have suggested that the
      memory of duration is distorted more for emotional events than for neutral
      events, while in contrast there is abundant evidence that other aspects of
      memories of emotional events are more accurate. To reconcile this apparent
      discrepancy, we used a procedure in which the participants learned a standard
      duration over several trials under three emotional conditions: a threatening, a
      nonthreatening, and a neutral control condition. They were then tested either
      immediately or 24 h after learning. In this test phase, they had to indicate
      whether presented comparison durations were or were not the same as the
      previously learned standard duration. We found that durations were recalled
      better in the emotional than in the neutral condition, and that this occurred to
      a greater extent in the threatening than in the nonthreatening condition.
      Arousing emotions thus enhanced temporal memory, just as they enhance memory for
      other aspects of emotional events.

PMID- 21948306
TI  - Silymarin glyceryl monooleate/poloxamer 407 liquid crystalline matrices: physical
      characterization and enhanced oral bioavailability.
AB  - Silymarin, a mixture of flavonolignans extracted from the seeds of milk thistle,
      is used clinically as a hepatoprotector to treat liver injuries and chronic
      hepatitis. However, its therapeutic effect is compromised by its poor oral
      bioavailability due to the poor solubility and low permeability across intestinal
      epithelia. The main purpose of this study was to prepare silymarin glyceryl
      monooleate/poloxamer 407 liquid crystalline matrices (GMO/P407 LCM) to improve
      the oral bioavailability of silymarin. GMO/P407 LCMs were prepared by a
      melting/congealing method. The isotropic phenomenon observed under polarized
      light microscope confirmed the liquid crystalline structure at the junction of
      LCM and water. Both differential scanning calorimetry and X-ray diffraction
      analysis confirmed disappearance of silymarin crystallinity after incorporation
      into the LCMs. In vitro release of silymarin from LCMs was limited, whereas LCMs
      were readily degraded by lipase and released silymarin quickly and completely.
      Pharmacokinetic study in beagle dogs showed significantly increased peak
      concentration for silymarin GMO/P407 LCM, and, most importantly, a 3.46-fold
      increase in oral bioavailability as compared with Legalon(r), a commercial
      silymarin formulation.

PMID- 21948307
TI  - Effect of different excipients on the physical characteristics of granules and
      tablets with carbamazepine prepared with polyethylene glycol 6000 by fluidized
      hot-melt granulation (FHMG).
AB  - The objective of this study was to investigate the properties of granules and
      tablets with carbamazepine which were prepared employing a fluidized hot-melt
      granulation (FHMG) technique. The FHMG process was carried out at 65 degrees C.
      Macrogol 6000 (PEG 6000) was used as a binder at the content 10% (w/w) of the
      granulated mass. Granules containing up to 70% (w/w) of the drug and 20-90% (w/w)
      of a filler (lactose, mannitol, calcium hydrogen phosphate (Di-Cafos),
      pregelatinized starch, and microcrystalline cellulose (MCC)) were produced. When
      the drug content was 30% (w/w), the yield of the process was satisfying (>95%)
      and flowability of the granules was better than placebo granules or drug-loaded
      granules prepared by wet granulation. Type of a filler had strong impact on
      physical properties of granules, and size distribution of the particles was the
      most homogenous when lactose or Di-Cafos were used. The FHMG technique enabled
      preparation of granules with better compressability compared with the wet
      granulated product or with non-granulated powders. Tablets with shorter
      disintegration time than 10 min were obtained with 2.0% crospovidone added as a
      disintegrant. In comparison to tablets prepared from the wet-granulated mass,
      employment of the FHMG method resulted in tablets with faster dissolution of
      carbamazepine (more than 80% of the drug released within 15 min). This was
      achieved with mannitol or lactose/MCC, as fillers.

PMID- 21948308
TI  - 50 Years Ago in CORR: Surgical approaches to the region of the shoulder joint
      Anthony F. DePalma MD CORR 1961;20:163-184.

PMID- 21948309
TI  - Epithelioid hemangioma of bone and soft tissue: a reappraisal of a controversial
      entity.
AB  - BACKGROUND: The controversy surrounding diagnosis of an epithelioid hemangioma
      (EH), particularly when arising in skeletal locations, stems not only from its
      overlapping features with other malignant vascular neoplasms, but also from its
      somewhat aggressive clinical characteristics, including multifocal presentation
      and occasional lymph node involvement. Specifically, the distinction from
      epithelioid hemangioendothelioma (EHE) has been controversial. The recurrent
      t(1;3)(p36;q25) chromosomal translocation, resulting in WWTR1-CAMTA1 fusion,
      recently identified in EHE of various anatomic sites, but not in EH or other
      epithelioid vascular neoplasms, suggests distinct pathogeneses.
      QUESTION/PURPOSES: We investigated the clinicopathologic and radiologic
      characteristics of bone and soft tissue EHs in patients treated at our
      institution with available tissue for molecular testing. PATIENTS AND METHODS:
      Seventeen patients were selected after confirming the pathologic diagnosis and
      fluorescence in situ hybridization analysis for the WWTR1 and/or CAMTA1
      rearrangements. Four patients had multifocal presentation. Most patients with EH
      of bone were treated by intralesional curettage. None of the patients died of
      disease and only four patients had a local recurrence. RESULTS: Our results,
      using molecular testing to support the pathologic diagnosis of EH, reinforce
      prior data that EH is a benign lesion characterized by an indolent clinical
      course with an occasional multifocal presentation and rare metastatic potential
      to locoregional lymph nodes. CONCLUSION: These findings highlight the importance
      of distinguishing EH from other malignant epithelioid vascular tumors as a result
      of differences in their management and clinical outcome. LEVEL OF EVIDENCE: Level
      IV, prognostic study. See Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 21948310
TI  - Stiffness and thickness of fascia do not explain chronic exertional compartment
      syndrome.
AB  - BACKGROUND: Chronic exertional compartment syndrome is diagnosed based on
      symptoms and elevated intramuscular pressure and often is treated with
      fasciotomy. However, what contributes to the increased intramuscular pressure
      remains unknown. QUESTIONS/PURPOSES: We investigated whether the stiffness or
      thickness of the muscle fascia could help explain the raised intramuscular
      pressure and thus the associated chronic compartment syndrome symptoms. PATIENTS
      AND METHODS: We performed plain radiography, bone scan, and intramuscular
      pressure measurement to diagnose chronic compartment syndrome and to exclude
      other disorders. Anterior tibialis muscle fascial biopsy specimens from six
      healthy individuals, 11 patients with chronic compartment syndrome, and 10
      patients with diabetes mellitus and chronic compartment syndrome were obtained.
      Weight-normalized fascial stiffness was assessed mechanically in a microtensile
      machine, and fascial thickness was analyzed microscopically. RESULTS: Mean
      fascial stiffness did not differ between healthy individuals (0.120 N/mg/mm; SD,
      0.77 N/mg/mm), patients with chronic compartment syndrome (0.070 N/mg/mm; SD,
      0.052 N/mg/mm), and patients with chronic compartment syndrome and diabetes
      (0.097 N/mg/mm; SD, 0.073 N/mg/mm). Similarly, no differences in fascial
      thickness were present. There was a negative correlation between fascial
      stiffness and intramuscular pressure in the patients with chronic compartment
      syndrome and diabetes. CONCLUSIONS: The lack of difference in fascial thickness
      and stiffness in patients with chronic compartment syndrome and patients with
      chronic compartment syndrome and diabetes compared with healthy individuals
      suggests structural and mechanical properties are unlikely to explain chronic
      compartment syndrome. To prevent chronic exertional compartment syndrome, it is
      necessary to address aspects other than the muscle fascia. LEVEL OF EVIDENCE:
      Level II, prognostic study. See the guidelines online for a complete description
      of level of evidence.

PMID- 21948311
TI  - Polyethylene wear is related to patient-specific contact stress in THA.
AB  - BACKGROUND: General numerical models of polyethylene wear and THA simulators
      suggest contact stresses influence wear. These models do not account for some
      patient-specific factors. Whether the relationship between patient-specific
      contact stress and wear apply in vivo is unclear. QUESTIONS/PURPOSES: We
      therefore determined whether (1) contact stress distribution at the prosthesis
      cup interface and (2) hip geometry and cup inclination are related to wear in
      vivo. METHODS: We retrospectively reviewed the radiographs of 80 patients who had
      aseptic loosening of their THAs as determined by radiographic criteria. We
      determined linear penetration and volumetric wear using postoperative and last
      followup radiographs. Contact stress distribution was determined by the HIPSTRESS
      method. The biomechanical model was scaled to fit the patient's musculoskeletal
      geometry of the pelvis, trochanteric position, and cup inclination using the
      standard postoperative radiograph. RESULTS: Linear penetration and volumetric
      wear correlated with peak contact stress. Polyethylene wear was greater in THAs
      with a medial position of the greater trochanter and smaller inclination of the
      acetabular cup. CONCLUSIONS: Our observations suggest wear is specific to contact
      stresses in vivo. CLINICAL RELEVANCE: Long-term wear in a THA can be estimated
      using contact stress analysis based on analysis of the postoperative AP
      radiograph.

PMID- 21948312
TI  - Rhodium-catalyzed intermolecular [2+2+2] cross-trimerization of aryl ethynyl
      ethers and carbonyl compounds to produce dienyl esters.

PMID- 21948313
TI  - Endotrol-tracheal tube assisted endotracheal intubation during video
      laryngoscopy.
AB  - Video laryngoscopes allow indirect visualization of the glottis and provide
      superior views of the glottis compared to direct laryngoscopes in patients with
      both normal and difficult airways, but it may be difficult to advance the
      endotracheal tube (ETT) through the vocal cords into the trachea, unless a stylet
      is used. We propose that the Endotrol((r)) ETT may be an effective tool to
      facilitate video laryngoscope-assisted orotracheal intubation without the use of
      a stylet. After obtaining written and oral informed consent, 60-adult patients
      scheduled for elective surgery requiring general anesthesia with orotracheal
      intubation were enrolled. Patients were randomized, respectively, to 1 of 4
      groups: Group A(1), (15 patients): McGrath((r)) with Endotrol((r)) ETT; Group
      A(2), (15 patients): McGrath((r)) with GlideRite((r))-styletted standard ETT;
      Group B(1), (15 patients): GlideScope((r)) with Endotrol((r)) ETT; Group B(2),
      (15 patients): GlideScope((r)) with GlideRite((r))-styletted standard ETT.
      Statistical analysis was performed with Stata (Stata Corp v10, College Station).
      Mean time to intubation was longer in the Endotrol((r)) groups compared to the
      GlideRite((r)) groups: 60.1 (31.6) vs. 44.4 (27.6) s (p < 0.05). It was
      subjectively more difficult to intubate using the Endotrol((r)) than with a
      GlideRite((r))-styletted ETT (difficulty score median [range] 2 [1-5] vs. 1 [1
      3], respectively). Three intubations using the Endotrol((r)) were characterized
      as difficult, whereas there were no difficult intubations with the
      GlideRite((r))stylet. The Endotrol((r)) ETT, as compared to a standard ETT with a
      non-malleable stylet, is associated with longer intubation times and a subjective
      increase in difficulty of use. It may, however, still be a clinically viable
      alternative in video laryngoscope-assisted orotracheal intubation when use of a
      rigid stylet is undesirable.

PMID- 21948314
TI  - Primary multifocal extranodal lymphoma of the kidneys, ovaries and bones: utility
      of FDG PET/CT.

PMID- 21948315
TI  - Suicide attempts versus nonsuicidal self-injury among individuals with anxiety
      disorders in a nationally representative sample.
AB  - BACKGROUND: This study is aimed to determine whether anxiety disorders are
      associated with suicide attempts with intent to die and to further investigate
      the characteristics of deliberate self-harm (DSH) among anxiety disorders.
      METHOD: Data came from the Collaborative Psychiatric Epidemiological Surveys (N =
      20,130; age 18 years and older; response rate = 72.3%). DSM-IV anxiety disorders
      were assessed using the World Mental Health Composite International Diagnostic
      Interview. People with an anxiety disorder endorsing a history of DSH were
      subcategorized as those who made suicide attempts (n = 159; individuals who
      intended to die), versus those who made nonsuicidal self-injuries (n = 85;
      individuals who did not intend to die). RESULTS: Anxiety disorders were
      associated with both suicide attempts and nonsuicidal self-injury (NSSI). People
      with generalized anxiety disorder and social phobia who engaged in DSH were more
      likely to have made a suicide attempt than a NSSI, independent of the effects of
      mood and substance use disorders. In addition, individuals with generalized
      anxiety disorder and social phobia who engaged in DSH were more likely to engage
      in this behavior multiple times, and at least one of those times was a suicide
      attempt. CONCLUSION: This study suggests that anxiety disorders are associated
      with suicide attempts with intent to die. Social phobia and generalized anxiety
      disorder appear to be associated with the more worrisome patterns of DSH
      including multiple suicide attempts.

PMID- 21948317
TI  - Synthesis, characterization, and light-controlled antibiotic application of a
      composite material derived from polyurethane and silica xerogel with embedded
      photoactive manganese nitrosyl.
AB  - The synthesis of a light-sensitive polyurethane-based composite material (PUX-NO)
      is described. In its polyurethane medium, PUX-NO contains entrapped silica
      xerogel particles in which a photoactive manganese nitrosyl has been
      incorporated. Green flexible films of PUX-NO readily release nitric oxide (NO)
      only when exposed to low power (mW) visible light. Incorporation of the nitrosyl
      in the xerogel not only retains the nitrosyl (NO donor) within the composite
      material but also provides the right extent of hydration. Pre-swelled films of
      PUX-NO have water content close to 30 Wt % and such films can be stored for
      months under slightly moist condition without loss in NO-delivering capacity. The
      NO-releasing parameters of the film have been determined. The NO-releasing
      capacity of PUX-NO films can be conveniently altered by changing the amount of
      the nitrosyl as well as the thickness of the films. Patches of PUX-NO film have
      been successfully employed to reduce drastically bacterial loads of both gram
      positive and gram-negative bacteria including methicillin-resistant
      Staphylococcus aureus and Acinetobacter baumannii under the total control of
      light. Effective control of infections by these bacterial pathogens via delivery
      of proper doses of NO only to the sites of infection appears feasible with PUX-NO
      films.

PMID- 21948316
TI  - Sex steroid hormones regulate the expression of growth-associated protein 43,
      microtubule-associated protein 2, synapsin 1 and actin in the ventromedial
      nucleus of the hypothalamus.
AB  - The ventromedial nucleus of the hypothalamus is well known for its involvement in
      the regulation of the female reproductive behavior. The dendritic trees of
      neurons in its ventrolateral division (VMNvl), the dendritic spines, and the
      dendritic and spine synapses undergo alterations along the estrous cycle. Because
      these changes are conspicuous, we thought of interest to examine the influence of
      sex steroids in the levels of the structural proteins of axons and dendrites. The
      VMNvl of female rats at all phases of the estrous cycle was labeled for growth
      associated protein-43, microtubule-associated protein 2, synapsin 1 and actin.
      The intensity of the labeling was measured using a modified Brightness-Area
      Product method that is sensitive to variations the size of the VMN. The
      brightness per unit area of these proteins did not undergo significant variations
      over the estrous cycle, except synapsin 1 that was significantly reduced in
      diestrus relative to the remaining phases of the ovarian cycle. Conversely, the
      Brightness-Area-Product of all labeled proteins changed along the estrous cycle
      and was greater at proestrus than at all other phases. Our results show the
      presence of estrous cycle-related oscillations in the levels of the structural
      proteins that are involved in dendritic and synaptic plasticity.

PMID- 21948318
TI  - Reactive impurities in excipients: profiling, identification and mitigation of
      drug-excipient incompatibility.
AB  - Reactive impurities in pharmaceutical excipients could cause drug product
      instability, leading to decreased product performance, loss in potency, and/or
      formation of potentially toxic degradants. The levels of reactive impurities in
      excipients may vary between lots and vendors. Screening of excipients for these
      impurities and a thorough understanding of their potential interaction with drug
      candidates during early formulation development ensure robust drug product
      development. In this review paper, excipient impurities are categorized into six
      major classes, including reducing sugars, aldehydes, peroxides, metals,
      nitrate/nitrite, and organic acids. The sources of generation, the analytical
      method for detection, the stability of impurities upon storage and processing,
      and the potential reactions with drug candidates of these impurities are
      reviewed. Specific examples of drug-excipient impurity interaction from internal
      research and literature are provided. Mitigation strategies and corrective
      measures are also discussed.

PMID- 21948319
TI  - Stability studies needed to define the handling and transport conditions of
      sensitive pharmaceutical or biotechnological products.
AB  - Many pharmaceutical or biotechnological products require transport using
      temperature-controlled systems to keep their therapeutic properties. There are
      presently no official guidelines for testing pharmaceutical products in order to
      define suitable transport specifications. After reviewing the current guidance
      documents, this paper proposes a methodology for testing pharmaceutical products
      and defining appropriate transport conditions.

PMID- 21948321
TI  - Sustained-release delivery of octreotide from biodegradable polymeric
      microspheres.
AB  - The study reports on the drug release behavior of a potent synthetic somatostatin
      analogue, octreotide acetate, from biocompatible and biodegradable microspheres
      composed of poly-lactic-co-glycolic acid (PLGA) following a single intramuscular
      depot injection. The serum octreotide levels of three Oakwood Laboratories
      formulations and one Sandostatin LAR((r)) formulation were compared. Three
      formulations of octreotide acetate-loaded PLGA microspheres were prepared by a
      solvent extraction and evaporation procedure using PLGA polymers with different
      molecular weights. The in vivo drug release study was conducted in male Sprague
      Dawley rats. Blood samples were taken at predetermined time points for up to 70
      days. Drug serum concentrations were quantified using a radioimmunoassay
      procedure consisting of radiolabeled octreotide. The three octreotide PLGA
      microsphere formulations and Sandostatin LAR((r)) all showed a two-phase drug
      release profile (i.e., bimodal). The peak serum drug concentration of octreotide
      was reached in 30 min for all formulations followed by a decline after 6 h.
      Following this initial burst and decline, a second-release phase occurred after 3
      days. This second-release phase exhibited sustained-release behavior, as the drug
      serum levels were discernible between days 7 and 42. Using pharmacokinetic
      computer simulations, it was estimated that the steady-state octreotide serum
      drug levels would be predicted to fall in the range of 40-130 pg/10 MUL and 20
      100 pg/10 MUL following repeat dosing of the Oakwood formulations and Sandostatin
      LAR((r)) every 28 days and every 42 days at a dose of 3 mg/rat, respectively.

PMID- 21948320
TI  - Advanced technologies for oral controlled release: cyclodextrins for oral
      controlled release.
AB  - Cyclodextrins (CDs) are used in oral pharmaceutical formulations, by means of
      inclusion complexes formation, with the following advantages for the drugs: (1)
      solubility, dissolution rate, stability, and bioavailability enhancement; (2) to
      modify the drug release site and/or time profile; and (3) to reduce or prevent
      gastrointestinal side effects and unpleasant smell or taste, to prevent drug-drug
      or drug-additive interactions, or even to convert oil and liquid drugs into
      microcrystalline or amorphous powders. A more recent trend focuses on the use of
      CDs as nanocarriers, a strategy that aims to design versatile delivery systems
      that can encapsulate drugs with better physicochemical properties for oral
      delivery. Thus, the aim of this work was to review the applications of the CDs
      and their hydrophilic derivatives on the solubility enhancement of poorly water
      soluble drugs in order to increase their dissolution rate and get immediate
      release, as well as their ability to control (to prolong or to delay) the release
      of drugs from solid dosage forms, either as complexes with the hydrophilic (e.g.,
      as osmotic pumps) and/or hydrophobic CDs. New controlled delivery systems based
      on nanotechnology carriers (nanoparticles and conjugates) have also been
      reviewed.

PMID- 21948322
TI  - Methotrexate-loaded chitosan- and glycol chitosan-based nanoparticles: a
      promising strategy for the administration of the anticancer drug to brain tumors.
AB  - Brain tumor treatment employing methotrexate (MTX) is limited by the efflux
      mechanism of Pg-p on the blood-brain barrier. We aimed to investigate MTX-loaded
      chitosan or glycol chitosan (GCS) nanoparticles (NPs) in the presence and in the
      absence of a coating layer of Tween 80 for brain delivery of MTX. The effect of a
      low Tween 80 concentration was evaluated. MTX NPs were formulated following the
      ionic gelation technique and size and zeta potential measurements were acquired.
      Transport across MDCKII-MDR1 monolayer and cytotoxicity studies against C6 glioma
      cell line were also performed. Cell/particles interaction was visualized by
      confocal microscopy. The particles were shown to be cytotoxic against C6 cells
      line and able to overcome MDCKII-MDR1 cell barrier. GCS-based NPs were the most
      cytotoxic NPs. Confocal observations highlighted the internalization of Tween 80
      coated fluorescent NPs more than Tween 80-uncoated NPs. The results suggest that
      even a low concentration of Tween 80 is sufficient for enhancing the transport of
      MTX from the NPs across MDCKII-MDR1 cells. The nanocarriers represent a promising
      strategy for the administration of MTX to brain tumors which merits further
      investigations under in vivo conditions.

PMID- 21948323
TI  - Reinfected revised TKA resolves with an aggressive protocol and antibiotic
      infusion.
AB  - BACKGROUND: Revision of failed two-stage revision TKA for infection is
      challenging, and amputation often is the only alternative. QUESTIONS/PURPOSES: We
      asked whether reinfection after two-stage revision for infection could be
      controlled with an aggressive revision protocol and intraarticular antibiotic
      infusion. METHODS: We retrospectively reviewed 18 patients (12 women, six men)
      who underwent revision for failed reimplantation between January 1999 and January
      2008. Mean time from revision for infection to rerevision for reinfection was 5
      months (range, 1-18 months). All knees were treated with an individualized
      protocol that included aggressive exposure, extensive debridement, uncemented
      components, closure with muscle flaps (seven knees) and other plastic surgery
      procedures (three knees), and direct antibiotic infusion through Hickman
      catheters for 6 weeks. Ten knees had one-stage revision; five had debridement,
      cement spacer, and revision surgery 3 to 4 months later; and three had extensive
      soft tissue reconstruction before revision surgery. The minimum followup was 2.3
      years (mean, 6.1 years; range, 2.3-12.0 years). RESULTS: The mean Knee Society
      scores improved from 33 preoperatively to 76. Seventeen of the 18 had control of
      infection and achieved durable fixation and a closed wound. One patient had
      recurrent infection 13 months after one-stage revision, was revised, and remained
      asymptomatic 28 months postoperatively after redebridement and vancomycin
      infusion for 6 weeks. In one patient, soft tissue closure was not obtained and
      the patient required amputation. CONCLUSIONS: Extensile exposure, debridement,
      and soft tissue flaps for closure combined with uncemented fixation of revision
      implants and antibiotic infusion into the knee controlled reinfection after
      revision TKA.

PMID- 21948324
TI  - Three-dimensional morphology of the knee reveals ethnic differences.
AB  - BACKGROUND: Studies have demonstrated sex differences in femoral shape and
      quadriceps angle raising a question of whether implant design should be sex
      specific. Much of this research has addressed shape differences within the
      Caucasian population and little is known about differences among ethnic groups.
      QUESTIONS/PURPOSES: We therefore asked: Do shape differences in the distal femur
      and proximal tibia exist among different ethnic groups and between the sexes in
      each ethnic population? And if ethnic differences exist, do they have a clinical
      impact on current TKA design? SUBJECTS AND METHODS: We analyzed 1000 normal adult
      knees (80 African American, 80 East Asian, and 860 Caucasian). Three-dimensional
      surface models were created for each bone and added to three-dimensional
      statistical bone atlases. Statistical shape analysis was conducted with a process
      combining principal components and multiple discriminate analyses. Eleven femoral
      and nine tibial measurements were calculated. RESULTS: We found differences in
      mean measurements between the sexes and ethnicities. Males had larger knees, with
      a mean 5-mm-larger anteroposterior dimension than females in all ethnicities.
      African American females had a 7.4-mm-deeper patellar groove, 2.3-mm-smaller
      tibial mediolateral dimension, and 2.5-mm-larger tibial anteroposterior dimension
      than Caucasian females. African American males had a 4.3-mm-larger femoral
      anteroposterior dimension, 10.1-mm-larger tibial mediolateral dimension, and 6-mm
      larger tibial anteroposterior dimension than Asian males. CONCLUSIONS: We
      identified differences in three-dimensional knee morphology among Caucasian,
      African American, and East Asian populations. Clinical studies will be required
      to determine whether these differences are important for implant design.

PMID- 21948325
TI  - Is an algorithmic approach to the treatment of recurrent dislocation after THA
      effective?
AB  - BACKGROUND: The indications for surgical techniques for treatment of recurrent
      hip dislocation after THA differ, and their rates of achievement of stability may
      not be similar. QUESTIONS/PURPOSES: We (1) describe our indications for different
      approaches for recurrent dislocation, (2) outline an algorithmic approach to the
      management of recurrently dislocating hips after THA, and (3) determine the
      overall rate of restoration of stability via this algorithmic approach and for
      each of four procedures with our indications. PATIENTS AND METHODS: We
      retrospectively reviewed 66 patients (69 hips) with revision THA for symptomatic
      recurrent dislocation from 1993 to 2008. We determined the rate of achievement of
      stability for the overall patient population and with each revision technique.
      Minimum followup was 2.8 years (mean, 7.8 years; range, 2.8-12.7 years). RESULTS:
      Fifty-one of the 69 hips (74%) had no further dislocations while nine (13%)
      required two revisions and nine (13%) required three or more revisions.
      Ultimately, all of the 69 hips (100%) were stable at followup. Use of a large (36
      mm-diameter) head, constrained cup, trochanteric advancement, correction of
      malposition, and a combination of techniques was effective in achieving stability
      in 67%, 68%, 86%, 91%, and 90% of cases, respectively. CONCLUSIONS: Separating
      the treatment of patients based primarily on the presence or absence of (1)
      component malposition, (2) an intact abductor mechanism, and (3) implants
      accommodating a large-diameter femoral head, we were able to achieve hip
      stability with one operation in 74% of cases. LEVEL OF EVIDENCE: Level IV,
      therapeutic study. See the Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 21948326
TI  - Spatial location and strength of BOLD activation in high-spatial-resolution fMRI
      of the motor cortex: a comparison of spin echo and gradient echo fMRI at 7 T.
AB  - The increased blood oxygenation level-dependent contrast-to-noise ratio at
      ultrahigh field (7 T) has been exploited in a comparison of the spatial location
      and strength of activation in high-resolution (1.5  mm isotropic) gradient echo
      (GE) and spin echo (SE), echo planar imaging data acquired during the execution
      of a simple motor task in five subjects. SE data were acquired at six echo times
      from 30 to 55  ms. Excellent fat suppression was achieved in the SE echo planar
      images using slice-selective gradient reversal. Threshold-free cluster
      enhancement was used to define regions of interest (ROIs) containing voxels
      showing significant stimulus-locked signal changes from the GE and average SE
      data. These were used to compare the signal changes and spatial locations of
      activated regions in SE and GE data. T(2) and T(2)* values were measured, with
      means of 48.3 +/- 1.1  ms and 36.5 +/- 3.4  ms in the SE ROI. In addition, we
      identified a dark band in SE images of the motor cortex corresponding to a region
      in which T(2) and T(2)* were significantly lower than in the surrounding grey
      matter. The fractional SE signal change in the ROI was found to vary linearly as
      a function of TE, with a slope that was dependent on the particular ROI assessed:
      the mean DeltaR(2) value was found to be 0.85 +/- 0.11  s(-1) for the SE ROI and 
      0.37 +/- 0.05  s(-1) for the GE ROI. The fractional signal change relative to the
      shortest TE revealed that the largest signal change occurred at a TE of 45  ms
      outside of the dark band. At this TE, the ratio of the fractional signal change
      in GE and SE data was found to be 0.48 +/- 0.05. Phase maps produced from high
      resolution GE images spanning the right motor cortex were used to identify veins.
      The GE ROI was found to contain 18% more voxels overlying the venous mask than
      the SE ROI.

PMID- 21948327
TI  - The state of neonatal transport services in the UK.
AB  - Neonatal transfer services across the UK have evolved at different rates, using a
      variety of approaches. Scotland, Northern Ireland and most recently Wales have
      adopted a more centralised approach than in England, where due to comparative
      population size transport services have developed alongside neonatal network
      boundaries. Despite considerable investment, transport provision remains variable
      in some areas and there are continuing issues common to most regions, including
      service provision and configuration, training, competencies and audit. Further
      development is required to optimise the use of available resources and develop
      benchmarking to ensure a high quality sustainable service.

PMID- 21948329
TI  - Dopamine D2 receptor gene polymorphisms in newborn infants of drug-using women.
AB  - OBJECTIVES: To determine the characteristics of dopamine D2 receptor gene (DRD2)
      polymorphisms in drug-exposed and unexposed neonates and the relationship to
      neonatal abstinence syndrome (NAS). DESIGN: Retrospective case-control analysis
      between drug-exposed and unexposed infants between DRD2 polymorphisms, drug
      exposure and NAS treatment. PATIENTS: Drug-exposed (n=48) and drug-free (n=49)
      infants born between March 1999 and December 2006. METHODS: Analysis of DNA for
      the Taq1A, -141Ins/Del and Ser311Cys DRD2 polymorphisms. Drug exposure was
      determined by antenatal maternal drug and alcohol history. Frequency measures of
      DRD2 polymorphisms were compared between drug-exposed infants, treatment NAS
      medication and with control infants. SETTING: Tertiary maternity hospital,
      Sydney, Australia. MAIN OUTCOME MEASURES: All infants were born in a good
      condition (25.7% <37 weeks gestation). Opiates (methadone and heroin) were used
      by 45 (93.8%) of drug-exposed mothers. The A2A2 allele was more common in drug
      exposed infants (37 (77.0%) versus 23 (46.9%), p=0.003) but the A1A2 allele was
      more common in control infants (23 (46.9%) versus 4 (8.3%), p=0.00002). The-ins
      allele was more common in control (39 (79.6%) versus 20 (41.7%), p=<0.01) and
      unmedicated drug-exposed (14/25 (56%) versus 5/23 (21.7%), p=0.02) infants. The
      majority of infants (41 (83.7%) controls versus 41 (85.4%), p=1.000) expressed
      the least common, Ser polymorphism. CONCLUSIONS: DRD2 polymorphisms are
      detectable from DNA obtained from stored blood spots. The -ins allele is more
      common in control and unmedicated drug-exposed infants. Further study is
      recommended to explore postneonatal outcomes especially in relation to
      neuropsychiatric behaviours.

PMID- 21948330
TI  - Taxonomy and conservation of Vietnam's primates: a review.
AB  - Vietnam has the highest number of primate taxa overall (24-27) and the highest
      number of globally threatened primate taxa (minimum 20) in Mainland Southeast
      Asia. Conservation management of these species depends in part on resolving
      taxonomic uncertainties, which remain numerous among the Asian primates. Recent
      research on genetic, morphological, and acoustic diversity in Vietnam's primates
      has clarified some of these uncertainties, although a number of significant
      classification issues still remain. Herein, we summarize and compare the major
      current taxonomic classifications of Vietnam's primates, discuss recent advances
      in the context of these taxonomies, and suggest key areas for additional research
      to best inform conservation efforts in a region crucial to global primate
      diversity. Among the most important next steps for the conservation of Vietnam's
      primates is a new consensus list of Asian primates that resolves current
      differences between major taxonomies, incorporates recent research advances, and
      recognizes units of diversity at scales below the species-level, whether termed
      populations, morphs, or subspecies. Priority should be placed on recognizing
      distinct populations, regardless of the species concept in use, in order to
      foster the evolutionary processes necessary for primate populations to cope with
      inevitable environmental changes. The long-term conservation of Vietnam's
      primates depends not only on an accepted and accurate taxonomy but also on
      funding for on-the-ground conservation activities, including training, and the
      continued dedication and leadership of Vietnamese researchers and managers.

PMID- 21948331
TI  - Dietary breadth and resource use of Francois' langur in a seasonal and disturbed
      habitat.
AB  - Previous studies of Trachypithecus species indicated that they were selective
      feeders that concentrated on relatively few food species/items. From January to
      December 2005, I quantified potential food availability and the food
      species/items eaten by five groups of Francois' langur (Trachypithecus francoisi)
      in the Mayanghe Nature Reserve (MNR), People's Republic of China. These langurs
      fed on 164 species, of which the top ten accounted for 51% of all feeding
      records. Langurs consumed more species (91) in the spring than in other seasons
      (73 summer, 75 autumn, and 67 winter), and only 38 species were consumed in all
      seasons. Nontree food species, such as bushes and lianas, accounted for 47% of
      the total feeding records and for a majority (68%) of the feeding records in
      winter. The annual diet consisted of leaves (64% of feeding records), fruit and
      seed (32%), and other nonfoliage items (4%); the langurs switched from being more
      folivorous in spring (93%) and summer (79%) to being more frugivorous in autumn
      (53%) and winter (56%). There was no correlation between the proportion of
      feeding records and the food availability in the most frequently consumed
      species, indicating that these langurs were selective feeders; there were
      significant correlations between consumption and abundance in both the entire set
      of 112 food species and the set of 86 infrequently consumed species, indicating
      that foods that are more available are eaten more frequently. It appeared that in
      the seasonal and disturbed habitat, feeding decisions and diet composition of the
      langur may be driven more by food availability, and less by animal's selectivity,
      than at other sites. The results indicate that Francois' langur copes with
      habitat alterations by broaden its dietary breadth; this has implications for the
      adaptive significance of dietary breadth, and has implications for future
      conservation strategies for species which exist in degraded habitats.

PMID- 21948332
TI  - Some consonants sound curvy: effects of sound symbolism on object recognition.
AB  - Two experiments explored the influence of consonant sound symbolism on object
      recognition. In Experiment 1, participants heard a word ostensibly from a foreign
      language (in reality, a pseudoword) followed by two objects on screen: a
      rectilinear object and a curvilinear object. The task involved judging which of
      the two objects was properly described by the unknown pseudoword. The results
      showed that congruent sound-symbolic pseudoword-object pairs produced higher task
      accuracy over three rounds of testing than did incongruent pairs, despite the
      fact that "hard" pseudowords (with three plosives) and "soft" pseudowords (with
      three nonplosives) were paired equally with rectilinear and curvilinear objects.
      Experiment 2 reduced awareness of the manipulation by including similar-shaped,
      target-related distractors. Sound symbolism effects still emerged, though the
      time course of these effects over three rounds differed from that in Experiment
      1.

PMID- 21948333
TI  - Biodegradation of medium chain hydrocarbons by Acinetobacter venetianus 2AW
      immobilized to hair-based adsorbent mats.
AB  - The natural attenuation of hydrocarbons can be hindered by their rapid dispersion
      in the environment and limited contact with bacteria capable of oxidizing
      hydrocarbons. A functionalized composite material is described herein, that
      combines in situ immobilized alkane-degrading bacteria with an adsorbent material
      that collects hydrocarbon substrates, and facilitates biodegradation by the
      immobilized bacterial population. Acinetobacter venetianus 2AW was isolated for
      its ability to utilize hydrophobic n-alkanes (C10-C18) as the sole carbon and
      energy source. Growth of strain 2AW also resulted in the production of a
      biosurfactant that aided in the dispersion of complex mixtures of hydrophobic
      compounds. Effective immobilization of strain 2AW to the surface of OttimatTM
      adsorbent hair mats via vapor phase deposition of silica provided a stable and
      reproducible biocatalyst population that facilitates in situ biodegradation of n
      alkanes. Silica-immobilized strain 2AW demonstrated ca. 85% removal of 1% (v/v)
      tetradecane and hexadecane within 24 h, under continuous flow conditions. The
      methodology for immobilizing whole bacterial cells at the surface of an
      adsorbent, for in situ degradation of hydrocarbons, has practical application in
      the bioremediation of oil in water emulsions. Published 2011 American Institute
      of Chemical Engineers Biotechnol Prog., 2011.

PMID- 21948334
TI  - V.A.C. instill therapy - indications and technical applications. Abstracts of the
      First V.A.C. Instill Symposium. Heidelberg, Germany. November 21, 2008.

PMID- 21948335
TI  - The scintigraphic index spleen/liver at 30 minutes predicts the success of
      splenectomy in persistent and chronic primary immune thrombocytopenia.
AB  - Splenectomy is considered the second-line of treatment in patients with chronic
      primary immune thrombocytopenia (ITP) in whom glucocorticoids have failed. Some
      patients do not respond to splenectomy or they have postoperative complications.
      Based on our previous experience using kinetic and scintigraphic parameters, we
      did a retrospective study with the aim of comparing all these parameters as a
      means of predicting the success of splenectomy in persistent and chronic primary
      ITP. Forty-one consecutive patients with chronic primary ITP refractory to
      prednisone, who had been splenectomized, were included in the study. The response
      to splenectomy was assessed by evaluating bleeding and platelet counts before and
      at different times after surgery. A complete platelet kinetic study was performed
      before the splenectomy using autologous (111) In-labeled platelets. The
      scintigraphic parameters measured included different indices between
      spleen/heart, liver/hearth, and spleen/liver. Thirty-six patients gave a complete
      response after splenectomy and five patients did not respond. A statistically
      significant difference between both groups was found with initial platelet
      recovery and with some scintigraphic indices which also showed a variable
      prediction value for the success of splenectomy. Among these indices, the
      spleen/liver at 30 minutes demonstrated a predictive value with a 100% of
      sensitivity and a 100% of specificity. CONCLUSION: some platelet kinetic
      parameters and scintigraphic indices, in particular the spleen/liver at 30
      minutes, were useful to predict the outcome of splenectomy in persistent and
      chronic primary ITP and, therefore, they should be taken into account when
      deciding whether or not to perform a splenectomy.

PMID- 21948336
TI  - The first detection of Toxoplasma gondii DNA in environmental fruits and
      vegetables samples.
AB  - Toxoplasma gondii infections are prevalent in humans and animals all over the
      world. The aim of the study was to estimate the occurrence of T. gondii oocysts
      in fruits and vegetables and determine the genotype of the parasites. A total
      number of 216 fruits and vegetables samples were taken from shops and home
      gardens located in the area of northern Poland. Oocysts were recovered with the
      flocculation method. Then, real-time polymerase chain reaction (PCR) targeting
      the B1 gene was used for specific T. gondii detection and quantification.
      Toxoplasma DNA was found in 21 samples. Genotyping at the SAG2 locus showed SAG2
      type I and SAG2 type II. This is the first investigation describing T. gondii DNA
      identification in a large number of fruits and vegetables samples with rapid
      molecular detection methods. The results showed that fruits and vegetables
      contaminated with T. gondii may play a role in the prevalence of toxoplasmosis in
      Poland.

PMID- 21948337
TI  - Suicide and mental illness: a clinical review of 15 years findings from the UK
      National Confidential Inquiry into Suicide.
AB  - INTRODUCTION: Suicide risk is most commonly associated with mental illness. In
      particular, suicide in people under mental health care presents distinct patterns
      of risk and opportunities for prevention due to their close proximity to
      specialist care. SOURCES OF DATA: The National Confidential Inquiry into Suicide
      and Homicide by People with Mental Illness (Inquiry) is a unique UK-wide national
      database of all suicide cases in contact with mental health services in the 12
      months preceding suicide. This review presents Inquiry findings from the
      beginning of the Inquiry in 1996 up to the present (2011) (15 years). AREAS OF
      AGREEMENT: Suicide varies substantially by socio-demographic (age, gender) and
      clinical features (e.g. diagnosis; care variables). Effective suicide prevention
      initiatives should incorporate research findings to inform clinical practice and
      policy. AREAS OF CONTROVERSY: Risk assessment remains one of the most difficult
      areas of clinical practice and management although all areas of clinical
      practice, research and policy development would benefit from continued high
      quality studies. GROWING POINTS: The Inquiry work has positively influenced
      mental health practice and policy in the UK. These changes include: falling
      suicide rates in mental health patients, informing suicide prevention strategies
      and developing safety checklists for mental health services. AREAS TIMELY FOR
      DEVELOPING RESEARCH: Investigating suicide in non-mental health settings,
      investigating suicide following different treatment services and investigating
      models of service delivery could usefully inform future directions for improving
      patient safety.

PMID- 21948338
TI  - Activation of liver X receptors attenuates endotoxin-induced liver injury in mice
      with nonalcoholic fatty liver disease.
AB  - BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is classically
      associated with insulin resistance and the inflammatory response, especially in
      the nonalcoholic steatohepatitis phase. The liver X receptors (LXRs) play a
      critical role in the regulation of cholesterol metabolism and inflammatory
      processes. METHODS: Wild-type C57BL/6 mice were fed a normal diet (ND) or a high
      fat (HF) diet for 8 weeks. Some ND- and HF-fed mice were treated (i.p.) with the
      LXR agonist T0901317 (30 mg/kg/day) for 7 days. Lipopolysaccharide (LPS, 50
      MUg/mouse) was then injected intraperitoneally to induce liver injury. The
      activation of MAPKs, NF-kappaB and the PI3K pathway was evaluated using Western
      blot. Bone marrow-derived macrophages (MDMs) were isolated from the femurs of
      C57BL/6 mice and cultured with or without T0901317 (20 MUmol/l). The expression
      of tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase
      (iNOS) was evaluated in vitro or in vivo using real-time PCR,
      immunohistochemistry, or Western blot. RESULTS: The LXR agonist T0901317
      attenuated LPS-induced liver injury in a murine model of NAFLD, reflected by
      reduced serum alanine aminotransferase and aspartate aminotransferase levels, and
      reduced liver histology changes. Activation of LXRs reduced TNF-alpha and iNOS
      expression through inhibiting JNK and the PI3K signaling pathway. An in vitro
      study demonstrated that the activation of LXR inhibited the expression of TNF
      alpha and iNOS in the MDMs of mice. CONCLUSIONS: Activation of LXRs attenuates
      LPS-induced liver injury in murine NAFLD through inhibiting the pro-inflammatory
      activity of macrophages.

PMID- 21948339
TI  - Safety, tolerability, and activity of ALV003: results from two phase 1 single,
      escalating-dose clinical trials.
AB  - BACKGROUND: Celiac disease is the most common hereditary autoimmune disease in
      humans. The only treatment option for non-refractory celiac disease patients is
      adherence to a strict life-long gluten-free diet, which often fails to normalize
      small bowel histology. ALV003 is a mixture of two proteases that degrades gluten
      and is in clinical development as an oral therapy for patients with celiac
      disease. AIMS: The safety, tolerability, and activity of ALV003 were assessed in
      two phase 1 clinical trials. METHODS: In study 1 (N = 28) the study drug was
      administered in the fasted state; in study 2 (N = 53) the study drug was
      administered together with a gluten-containing meal. Both studies were single
      dose, single-blind, placebo-controlled, cross-over trials. ALV003 was dosed at
      escalating dose levels by cohort (100, 300, 900, and 1,800 mg) and gastric
      samples were aspirated using a nasogastric tube. Adverse events, serum drug
      levels, and anti-drug antibody titers were measured. Gastric samples were
      assessed for ALV003 enzymatic activity over time (gastric pharmacokinetics) and
      gluten degradation (gastric pharmacodynamics). RESULTS: All doses were well
      tolerated, and no serious adverse events or allergic reactions were observed.
      Gastric aspirates collected 30 min following a meal showed that 100 and 300 mg
      ALV003 degraded 75 +/- 10% (N = 8) and 88 +/- 5% (N = 8), respectively, of one
      gram of wheat bread gluten. CONCLUSIONS: ALV003 is an orally active protease that
      appears to be stable in the fed stomach and degrades dietary gluten in this
      compartment. Single doses of oral ALV003 were not associated with serious adverse
      reactions.

PMID- 21948340
TI  - Metallic or plastic stent for bile duct obstruction in ampullary cancer?
AB  - BACKGROUND AND AIMS: Although ampullary cancer is a relatively uncommon
      malignancy, it is frequently associated with biliary obstruction. Endoscopic
      biliary drainage is regarded as a palliative treatment of choice for patients
      with inoperable ampullary cancer. However, there are no data concerning choice of
      stent in this patient population. The objective of this study was to compare the
      efficacy of metallic and plastic stents for biliary obstruction in patients with
      ampullary cancer. METHODS: Thirty-seven patients (15 men and 22 women; median age
      74.7 years) with ampullary cancer treated with endoscopic biliary drainage were
      enrolled. Metallic and two plastic stents were placed in 17 and 20 patients,
      respectively. Clinical success, stent patency, and stent malfunction were
      evaluated. RESULTS: Clinical success was achieved in all patients (100%). The
      median period of stent patency was 132.7 days in the metallic stent group and
      128.5 days in the plastic stent group (P > 0.05). Stent malfunctions developed in
      17 and 19 patients in the metallic and plastic stent groups, respectively. Stent
      occlusion occurred in 15 (88.2%) and 15 (75%) patients and stent migration
      occurred in two (11.8%) and four (20%) patients in the metallic and plastic stent
      groups, respectively. CONCLUSIONS: Endoscopic biliary drainage using metallic or
      plastic stents is effective for initial endoscopic palliation in patients with
      obstructive jaundice because of ampullary cancer. Although metallic and plastic
      stents had similar clinical effect, it seems reasonable to choose two plastic
      stents as the first option in patients with ampullary cancer considering the cost
      effectiveness.

PMID- 21948341
TI  - Causes of esophageal food bolus impaction in the pediatric population.
AB  - BACKGROUND: Esophageal food bolus impaction is an uncommon entity in the
      pediatric population that presents with the acute onset of dysphagia, pain, and
      vomiting. The causes of esophageal food bolus impaction are thought to be
      different in the pediatric population as compared to adults. AIM: The purpose of
      this study was to determine the frequency of the different causes of food
      impaction in patients who undergo an esophagram or upper GI examination. METHODS:
      The radiology report database was searched to identify all patients with an
      esophageal food bolus impaction diagnosed on upper GI or esophagram between 1993
      and 2009. Two pediatric radiologists then evaluated each esophagram to determine
      the location of the filling defect within the esophagus. Finally, the electronic
      medical record was queried to identify demographic information and abnormalities
      associated with the food impaction. RESULTS: After querying the radiology
      database, 43 patients were identified with an impacted food bolus on esophagram
      or upper GI. There were three abnormalities associated with food impaction:
      eosinophilic esophagitis (23/43; 53%), prior esophageal atresia repair (11/43;
      26%), and prior Nissen fundoplication (5/43; 12%). There were eight patients in
      whom no underlying abnormality was identified. CONCLUSIONS: Eosinophilic
      esophagitis is the major abnormality associated with food bolus impaction in
      pediatric patients followed by narrowing at the site of prior esophageal or
      esophageal-related surgery.

PMID- 21948342
TI  - Evaluation of host inflammatory responses of beta-tricalcium phosphate
      bioceramics caused by calcium pyrophosphate impurity using a subcutaneous model.
AB  - Implantation of synthetic materials into body elicits inflammatory host responses
      that limit medical device integration and biological performance. Since the
      effective use of biomaterials in vivo requires good biocompatibility and bio
      functionality, it is vital that we assess the inflammatory reactions provoked by
      various implanted biomaterials. In chemical precipitation of beta-tricalcium
      phosphate [beta-Ca3(PO4)2, beta-TCP], the impurity of calcium pyrophosphate
      (Ca2P2O7, CPP) will easily appear if the preparation conditions are not well
      controlled. To test the influences of CCP-impurity on the biocompatibility of the
      material, four groups of beta-TCP ceramic samples doped with 0.5-10 wt % of CCP
      impurity, and pure beta-TCP and CCP samples were fabricated and implanted in rat
      subcutaneous site for one, two, and four weeks. The host tissue responses to the
      ceramics were evaluated by histomorphometric analysis, and the results were
      compared with pure beta-TCPbioceramics. The results show that the CPP impurity
      can elicit and stimulate the inflammatory responses at the tissue/implant
      interface. Moreover, with the increase of CPP doping amount, the inflammation
      increases apparently. However, the pure beta-TCP bioceramics only present slight
      post-implantation inflammatory responses. The influence of the CPP doping on the
      inflammatory responses is mainly related to a microparticles release because of
      an insufficient sintering of beta-TCP by CPP doping. The microparticle release
      could be at the origin of local inflammation and cell/tissue damages. Therefore,
      to obtain perfect biocompatibility and high quality beta-TCP bioceramics, it is
      important to avoid and control the CPP impurity in the preparation of beta-TCP
      powders and bioceramics.

PMID- 21948343
TI  - Pd(II)-catalyzed C-H olefination of N-(2-pyridyl)sulfonyl anilines and
      arylalkylamines.

PMID- 21948345
TI  - Radiation dose associated with coronary CT angiography and invasive coronary
      angiography: an experimental study of the effect of dose-saving strategies.
AB  - This study was conducted on a human anthropomorphic phantom to investigate the
      effective dose and entrance skin dose (ESD) in selected radiosensitive organs
      through invasive and computed tomography (CT) coronary angiography procedures
      using different dose-saving techniques. The effective dose was calculated as
      2.49, 3.35 and 9.62 mSv, respectively, corresponding to three coronary CT
      angiography protocols, including prospective ECG gating and retrospective ECG
      gating with and without tube current modulation. In comparison, the effective
      dose was calculated as 7.26, 6.35, 5.58 and 4.71 mSv at four different
      magnifications acquired with invasive coronary angiography. The highest ESD was
      measured in the breast during the coronary CT angiography and in the thyroid
      gland during invasive coronary angiography. Although invasive coronary
      angiography produces lower radiation dose than coronary CT angiography,
      application of modified techniques in both CT and invasive coronary angiography
      is recommended in clinical practice for radiation dose reduction.

PMID- 21948344
TI  - ConBr, a lectin from Canavalia brasiliensis seeds, protects against quinolinic
      acid-induced seizures in mice.
AB  - Lectins are proteins capable of reversible binding to carbohydrates or
      glycoconjugates. In the central nervous system of mammals, lectins with affinity
      for mannose/glucose or galactose can modulate cellular communication. ConBr, a
      lectin isolated from the seeds of Canavalia brasiliensis, previously showed
      antidepressant effect in the forced swimming test in mice, with involvement of
      the monoaminergic system. In this study, we investigated the neuroprotective
      effects of ConBr against quinolinic acid (QA), a well-known NMDA agonist that
      produces severe neurotoxicity when administered in vivo. ConBr (10 MUg/site)
      administered via intracerebroventricular (i.c.v.) showed a neuroprotective
      activity against seizures induced by QA (36.8 nmol/site; i.c.v.) when
      administered 15 min prior to QA, with a percentage of protection around 50%.
      ConBr was also able to significantly decrease the severity of the seizures but
      without changes in the latency of the first convulsion or the duration of the
      seizures. This effect was dependent on the structural integrity of the ConBr
      protein and its binding capacity to oligosaccharides residues. ConA, a lectin
      with high similarity to ConBr, did not reverse the QA-induced seizures. Moreover,
      ConBr was able to protect against hippocampal cell death caused by QA, which was
      measured by propidium iodide incorporation. QA caused activation of JNK2 and
      improved the phosphorylation of Ser831 and 845 on the AMPA receptor GluR1
      subunit, and both of these effects were counteracted by ConBr. Our data suggest
      that the lectin ConBr may exert a modulatory action on NMDA receptors, which
      inhibits its activity in response to QA.

PMID- 21948346
TI  - Acute gout at engraftment following hematopoietic transplantation.

PMID- 21948347
TI  - Arginine-aromatic interactions and their effects on arginine-induced
      solubilization of aromatic solutes and suppression of protein aggregation.
AB  - We examine the interaction of aromatic residues of proteins with arginine, an
      additive commonly used to suppress protein aggregation, using experiments and
      molecular dynamics simulations. An aromatic-rich peptide, FFYTP (a segment of
      insulin), and lysozyme and insulin are used as model systems. Mass spectrometry
      shows that arginine increases the solubility of FFYTP by binding to the peptide,
      with the simulations revealing the predominant association of arginine to be with
      the aromatic residues. The calculations further show a positive preferential
      interaction coefficient, Gamma(XP), contrary to conventional thinking that
      positive Gamma(XP)'s indicate aggregation rather than suppression of aggregation.
      Simulations with lysozyme and insulin also show arginine's preference for
      aromatic residues, in addition to acidic residues. We use these observations and
      earlier results reported by us and others to discuss the possible implications of
      arginine's interactions with aromatic residues on the solubilization of aromatic
      moieties and proteins. Our results also highlight the fact that explanations
      based purely on Gamma(XP), which measures average affinity of an additive to a
      protein, could obscure or misinterpret the underlying molecular mechanisms behind
      additive-induced suppression of protein aggregation.

PMID- 21948348
TI  - Collaborative assessment and management of suicidality (CAMS): feasibility trial
      for next-day appointment services.
AB  - BACKGROUND: Despite the ubiquity of suicidality in behavioral health settings,
      empirically supported interventions for suicidality are surprisingly rare. Given
      the importance of resolving suicidality and therapists' anxieties about treating
      suicidal patients, there is a clear need for innovative services and clinical
      approaches. The purpose of the current study was an attempt to address some of
      these needs by examining the feasibility and use of a new intervention called the
      "Collaborative Assessment and Management of Suicidality" (CAMS) within a "Next
      Day Appointment" (NDA) outpatient treatment setting. METHODS: As part of a larger
      feasibility study, n = 32 suicidal patients were randomly assigned to CAMS care
      versus Enhanced Care as Usual (E-CAU) in an outpatient crisis intervention
      setting attached to a safety net hospital. Intent to treat suicidal patients were
      seen and assessed before, during, and after treatment (with follow-up assessments
      conducted at 2, 4, 6, and 12 months). RESULTS: The feasibility of using CAMS in
      the NDA setting was clear; both groups appeared to initially benefit from their
      respective treatments in terms of decreased suicidal ideation and overall symptom
      distress. Although patients rated both treatments favorably, the CAMS group had
      significantly higher satisfaction and better treatment retention than E-CAU. At
      12 months post-treatment, CAMS patients showed significantly better and sustained
      reductions in suicidal ideation, overall symptom distress, and increased hope in
      comparison to E-CAU patients. CONCLUSIONS: CAMS was both feasible in this NDA
      setting and effective in treating suicidal ideation, distress, and hopelessness
      (particularly at 12 months followup).

PMID- 21948349
TI  - Representations in mental imagery and working memory: evidence from different
      types of visual masks.
AB  - Although few studies have systematically investigated the relationship between
      visual mental imagery and visual working memory, work on the effects of passive
      visual interference has generally demonstrated a dissociation between the two
      functions. In four experiments, we investigated a possible commonality between
      the two functions: We asked whether both rely on depictive representations.
      Participants judged the visual properties of letters using visual mental images
      or pictures of unfamiliar letters stored in short-term memory. Participants
      performed both tasks with two different types of interference: sequences of
      unstructured visual masks (consisting of randomly changing white and black dots)
      or sequences of structured visual masks (consisting of fragments of letters). The
      structured visual noise contained elements of depictive representations (i.e.,
      shape fragments arrayed in space), and hence should interfere with stored
      depictive representations; the unstructured visual noise did not contain such
      elements, and thus should not interfere as much with such stored representations.
      Participants did in fact make more errors in both tasks with sequences of
      structured visual masks. Various controls converged in demonstrating that in both
      tasks participants used representations that depicted the shapes of the letters.
      These findings not only constrain theories of visual mental imagery and visual
      working memory, but also have direct implications for why some studies have
      failed to find that dynamic visual noise interferes with visual working memory.

PMID- 21948350
TI  - Temporal-contextual processing in working memory: evidence from delayed cued
      recall and delayed free recall tests.
AB  - Three experiments are reported that addressed the nature of processing in working
      memory by investigating patterns of delayed cued recall and free recall of items
      initially studied during complex and simple span tasks. In Experiment 1, items
      initially studied during a complex span task (i.e., operation span) were more
      likely to be recalled after a delay in response to temporal-contextual cues,
      relative to items from subspan and supraspan list lengths in a simple span task
      (i.e., word span). In Experiment 2, items initially studied during operation span
      were more likely to be recalled from neighboring serial positions during delayed
      free recall than were items studied during word span trials. Experiment 3
      demonstrated that the number of attentional refreshing opportunities strongly
      predicts episodic memory performance, regardless of whether the information is
      presented in a spaced or massed format in a modified operation span task. The
      results indicate that the content-context bindings created during complex span
      trials reflect attentional refreshing opportunities that are used to maintain
      items in working memory.

PMID- 21948351
TI  - Considerations on what constitutes a 'qualified statistician' in regulatory
      guidelines.
AB  - International regulatory guidelines require that a 'qualified statistician' takes
      responsibility for the statistical aspects of a clinical trial used for drug
      licensing. No consensus on what constitutes a 'qualified statistician' appears to
      have been developed so far. The International Society for Clinical Biostatistics
      is issuing this reflection paper in order to stimulate a discussion on the
      concept.

PMID- 21948352
TI  - A 40-year-old man with recurrent fainting, hypotension, lower limb edema and
      oliguria with body weight gain and secondary erythrocytosis.

PMID- 21948353
TI  - Shifting from Ziegler-Natta to Philips-type catalyst? A simple and safe access to
      reduced titanium systems for ethylene polymerization.
AB  - Silica-supported titanium(IV) chloride is readily reduced by Mashima and co
      workers' reagent (1-methyl-3,6-bis(trimethylsilyl)-1,4-cyclohexadiene) to afford
      materials active in ethylene polymerisation without need of aluminum alkyl
      cocatalyst.

PMID- 21948354
TI  - Connexin 43 and metabolic effect of fatty acids in stressed endothelial cells.
AB  - Changes in the inner mitochondrial membrane potential (?psi) may lead either to
      apoptosis or to protective autophagy. Connexin 43 (Cx43), a gap junction protein,
      is suggested to affect mitochondrial membrane permeability. The aim of our study
      was to analyze Cx43 gene expression, Cx43 protein localization and mitochondrial
      function in the human endothelial cells stressed by dietary-free fatty acids
      (FFA) and TNFalpha. Human endothelial cells (HUVECs) were incubated with (10-30
      uM) palmitic (PA), oleic (OA), eicosapentaenoic (EPA) or arachidonic (AA) acids
      for 24 h. TNFalpha (5 ng/ml) was added at the last 4 h of incubation. The Cx43
      gene expression was analyzed by the quantitative real-time PCR. The Cx43 protein
      concentrations in whole cells and in the isolated mitochondria were measured.
      Changes in ?psi and Cx43 localization were analyzed by flow cytometry or
      fluorescence microscopy. Generated ATP was measured by a luminescence assay.
      TNFalpha, PA and OA significantly decreased ?psi, while AA (P = 0.047) and EPA (P
      = 0.004) increased ?psi value. Preincubation with EPA or AA partially prevented
      the TNFalpha-induced decrease of ?psi. Incubation with AA resulted in up
      regulation of the Cx43 gene expression. AA or PA significantly increased Cx43
      protein content; however, presence of TNFalpha in general aggravated the negative
      effect of FFA. Only EPA was found to increase ATP generation in HUVECs. The fatty
      acid-specific induction of changes in Cx43 expression and protein concentration
      as well as the normalization of ?psi and increase of ATP generation seem to be
      the separate, independent mechanisms of FFA-mediated modulatory effect in the
      human endothelial cells pathology.

PMID- 21948355
TI  - Long-term outcome of rifaximin therapy in non-constipation irritable bowel
      syndrome.

PMID- 21948357
TI  - Histological versus clinical cirrhosis in chronic hepatitis C: does
      race/ethnicity really matter?
AB  - Liver fibrosis progression in hepatitis C virus (HCV) infection has been in part
      associated with race/ethnicity. Little is known of the frequency of clinical
      cirrhosis in Asian patients in the US. AIM: To compare histological and clinical
      features of chronic hepatitis C (CHC) in a multiethnic cohort of patients.
      METHODS: Retrospective query of an electronic medical registry for CHC patients
      evaluated from 1999 to 2005. Histological cirrhosis was defined as advanced
      METAVIR fibrosis score at biopsy. Clinical cirrhosis was defined as any of:
      varices, ascites, or splenomegaly. Liver cirrhosis was defined as either
      histological or clinical cirrhosis. Chi-square tests, t tests, and logistic
      regression method were used for data analysis. RESULTS: Six hundred and ninety
      two patients were categorized into four racial-ethnic groups: 292 Caucasian (C),
      145 Hispanic (H), 121 African American (AA), and 134 Asian (As) patients. Median
      age of AA (54 years) and As (53) was higher than C (52), or H (50) (p < 0.05). H
      patients had a higher percentage of alcohol abuse (60%) than AA and C (42-44%)
      and As (14%; p < 0.0001). Body mass index (BMI) was significantly lower in Asians
      compared to all other groups (p < 0.0001). Features of the metabolic syndrome
      were common, ranging from 28% in As to 72% in H patients. Liver cirrhosis was
      found in 53% H, 35% C, 29% As, and 19% AA. In multivariable analysis, only
      alcohol abuse, BMI, diabetes mellitus (DM), and age were significantly associated
      with liver cirrhosis. There was a trend for AA to have less cirrhosis, either
      histological or clinical (p = 0.08). CONCLUSIONS: Using only histology, liver
      cirrhosis was significantly underestimated. In our cohort, severity of CHC was
      not clearly affected by race when alcohol use and features of the metabolic
      syndrome were taken into consideration. However, there was a trend for African
      Americans to have lower cirrhosis rates.

PMID- 21948356
TI  - Radiofrequency ablation for dysplasia in Barrett's esophagus restores beta
      catenin activation within esophageal progenitor cells.
AB  - BACKGROUND AND AIMS: Endoscopic therapies for Barrett's esophagus (BE) associated
      dysplasia, particularly radiofrequency ablation (RFA), are popular alternatives
      to surgery. The effect of such therapies on dysplastic stem/progenitor cells
      (SPC) is unknown. Recent studies suggest that AKT phosphorylation of beta-Catenin
      occurs in SPCs and may be a marker of activated SPCs. We evaluate the effect of
      RFA in restoring AKT-mediated beta-Catenin signaling in regenerative epithelium.
      METHODS: Biopsies were taken from squamous, non-dysplastic BE, dysplastic BE and
      esophageal adenocarcinoma (EAC). Also, post-RFA, biopsies of endoscopically
      normal appearing neosquamous epithelium were taken at 3, 6, and 12 months after
      successful RFA. Immunohistochemistry and Western blot analysis was performed for
      Pbeta-Catenin(552) (Akt-mediated phosphorylation of beta-Catenin), Ki-67 and p53.
      RESULTS: There was no difference in Pbeta-Catenin552 in squamous, GERD, small
      bowel and non-dysplastic BE. There was a fivefold increase in Pbeta-Catenin(552)
      in dysplasia and EAC compared to non-dysplastic BE (P < 0.05). Also, there was a
      persistent threefold increase in Pbeta-Catenin(552) in neosquamous epithelium 3
      months after RFA compared to native squamous epithelium (P < 0.05) that
      correlated with increased Ki-67. Six months after RFA, Pbeta-Catenin(552) and Ki
      67 are similar to native squamous epithelium. CONCLUSIONS: Enhanced AKT-mediated
      beta-Catenin activation is seen in BE-associated carcinogenesis. Three months
      after RFA, squamous epithelial growth from SPC populations exhibited increased
      levels of Pbeta-Catenin(552). This epithelial response becomes quiescent at 6
      months after RFA. These data suggest that elevated Pbeta-Catenin(552) after RFA
      denotes a repair response in the neosquamous epithelium 3 months post-RFA.

PMID- 21948358
TI  - Tongue hyperpigmentation resulting from peginterferon alfa-2b and ribavirin
      treatment in a patient with chronic hepatitis C.
AB  - Hepatitis C virus (HCV) infection has been associated with several cutaneous
      diseases such as lichen planus, porphyria cutanea tarda, chronic pruritus, and
      cutaneous necrotizing vasculitis (Doutre, Arch Dermatol 135:1401-1403, 1999). The
      antiviral treatment for chronic HCV with interferon alfa (INF) or peginterferon
      alfa (PEG-INF) combined with rivabirin also leads to many skin side effects
      including injection site reaction, generalized skin rashes, pruritus, dry skin,
      alopecia, and exacerbation of autoimmune processes, particularly psoriasis,
      lichen planus or vitiligo (Dalekos et al., Eur J Gastroenterol Hepatol 10:933
      939, 1998; Sookoian et al., Arch Dermatol 135:1000-1000, 1999). There are case
      reports of tongue hyperpigmentation during combination therapy of PEG IFN and RBV
      in chronic hepatitis C both in dark-skined as well as Caucasian. We report the
      first case of tongue hyperpigmentation associated with PEG-INF-2b plus ribavirin
      administration in a non-Caucasian patient with genotype 4.

PMID- 21948359
TI  - Pentraxins in humoral innate immunity.
AB  - Innate immunity represents the first line of defence against pathogens and plays
      key roles in activation and orientation of the adaptive immune response. The
      innate immune system comprises both a cellular and a humoral arm. Components of
      the humoral arm include soluble pattern recognition molecules (PRMs) that
      recognise pathogens associated molecular patterns (PAMPs) and initiate the immune
      response in coordination with the cellular arm, therefore acting as functional
      ancestors of antibodies. The long pentraxin PTX3 is a prototypic soluble PRM that
      is produced at sites of infection and inflammation by both somatic and immune
      cells. Gene targeting of this evolutionarily conserved protein has revealed a non
      redundant role in resistance to selected pathogens. Moreover, PTX3 exerts
      important functions at the crossroad between innate immunity, inflammation and
      female fertility. Here we review the studies on PTX3, with emphasis on pathogen
      recognition and crosstalk with other components of the innate immune system.

PMID- 21948361
TI  - The role of innate immunity in trafficking of hematopoietic stem cells-an
      emerging link between activation of complement cascade and chemotactic gradients
      of bioactive sphingolipids.
AB  - Hematopoietic stem and progenitor cells (HSPCs) circulate under steady-state
      conditions at detectable levels in peripheral blood (PB). The phenomenon of
      enforced release of HSPCs from BM into PB is called mobilization and may be
      envisioned as a danger-sensing response mechanism triggered by hypoxia or
      mechanical- or infection-induced tissue damage and is a part of stress response.
      It is unquestionable that the a-chemokine stromal derived factor-1 (SDF-1)-CXCR4
      axis plays crucial role in retention of HSPCs in BM. However, all factors that
      direct mobilization of HSPCs into PB and homing back to the BM or their
      allocation to damaged organs are not characterized very well. In this chapter we
      will present mounting evidence that elements of innate immunity such as
      complement cascade (CC) cleavage fragments (e.g., C3a and C5a), granulocytes,
      generation of membrane attack complex (MAC) together with sphingosine-1 phosphate
      (S1P) orchestrate HSPC mobilization. On other hand some other bioactive lipids
      e.g., ceramide-1-phosphate (C1P) that is released from damaged/"leaky" cells in
      BM after myeloablative conditioning for transplant may play an opposite important
      role in homing of HSPCs to BM. Finally, the chemotactic activity of all
      chemoattractants for HSPCs including SDF-1, S1P and C1P is enhanced in presence
      of CC cleavage fragments (e.g., C3a) and MAC that is a final product of CC
      activation.

PMID- 21948360
TI  - Galectins as pattern recognition receptors: structure, function, and evolution.
AB  - Galectins constitute an evolutionary conserved family of beta-galactoside-binding
      proteins, ubiquitous in mammals and other vertebrate taxa, invertebrates, and
      fungi. Since their discovery in the 1970s, their biological roles, initially
      understood as limited to recognition of carbohydrate ligands in embryogenesis and
      development, have expanded in recent years by the discovery of their
      immunoregulatory activities. A gradual paradigm shift has taken place in the past
      few years through the recognition that galectins also bind glycans on the surface
      of potentially pathogenic microbes, and function as recognition and effector
      factors in innate immunity. Further, an additional level of functional complexity
      has emerged with the most recent findings that some parasites "subvert" the
      recognition roles of the vector/host galectins for successful attachment or
      invasion.

PMID- 21948362
TI  - Interaction of the microbiome with the innate immune response in chronic wounds.
AB  - Microbes colonizing and/or infecting chronic wounds undoubtedly play a major and
      interactive role in impaired healing, especially in amplifying and perpetuating
      the host innate immune response. The development of molecular techniques to
      identify and quantify microbial organisms has revolutionized our view of the
      microbial world. These less-biased, high throughput methods greatly enable
      investigations regarding host-microbe interactions in the chronic wound
      environment. This review focuses on the mounting evidence implicating microbes
      and excessive inflammation in chronic wounds, as well as the challenges
      associated with understanding how microbes modulate wound healing and the innate
      immune response.

PMID- 21948364
TI  - A conserved host and pathogen recognition site on immunoglobulins: structural and
      functional aspects.
AB  - A common site in the constant region (Fc) of immunoglobulins is recognized by
      host receptors and is a frequent target of proteins expressed by pathogens. This
      site is located at the junction of two constant domains in the antibody heavy
      chains and produces a large shallow cavity formed by loops of the CH2 and CH3
      domains in IgG and IgA (CH3 and CH4 domains in IgM). Crystal structures have been
      determined for complexes of IgG-Fc and IgA-Fc with a structurally diverse set of
      host, pathogen and in vitro selected ligands. While pathogen proteins may
      directly block interactions with the immunoglobulins thereby evading host
      immunity, it is likely that the same pathogen molecules also interact with other
      host factors to carry out their primary biological function. Herein we review the
      structural and functional aspects of host and pathogen molecular recognition of
      the common site on the Fc of immunoglobulins. We also propose that some pathogen
      proteins may promote virulence by affecting the bridging between innate and
      adaptive immunity.

PMID- 21948363
TI  - Pathogenic microbes and community service through manipulation of innate
      immunity.
AB  - The periodontal pathogen Porphyromonas gingivalis undermines major components of
      innate immunity, such as complement, Toll-like receptors (TLR), and their
      crosstalk pathways. At least in principle, these subversive activities could
      promote the adaptive fitness of the entire periodontal biofilm community. In this
      regard, the virulence factors responsible for complement and TLR exploitation
      (gingipain enzymes, atypical lipopolysaccharide molecules, and fimbriae) are
      released as components of readily diffusible membrane vesicles, which can thus
      become available to other biofilm organisms. This review summarizes important
      immune subversive tactics of P. gingivalis which might enable it to exert a
      supportive impact on the oral microbial community.

PMID- 21948366
TI  - Granzyme B: a new crossroad of complement and apoptosis.
AB  - In response to severe tissue trauma, several "molecular danger" sensing and
      signaling pathways are activated, especially the complement and the apoptosis
      cascade. Although possible crossroads between both systems have been proposed,
      little is known about the underlying molecular interactions. In this study a new
      interaction interface is presented for C3a and C5a generation by the pro
      apoptotic factor granzyme B. In vitro incubation of the central human complement
      components C3 and C5 with the serine protease granzyme B resulted in a
      concentration-dependent production of the anaphylatoxins C3a and C5a. The so
      generated anaphylatoxin C5a was chemotactic active for isolated human
      neutrophils. In a translational approach, intracellular granzyme B concentration
      in leukocytes was determined early after severe tissue trauma. In comparison to
      healthy volunteers, multiple injured patients (less than one hour after trauma,
      Injury Severity Score > 18, n = 5) presented a significant increase in granzmye B
      levels in neutrophils and lymphocytes. Thus, tissue trauma is associated with
      early activation of both, the complement and apoptosis system. The present data
      suggest a new form of interaction between the complement and the apoptosis system
      on the level of granzyme B that is capable to generate C3a and C5a independently
      of the established complement proteases.

PMID- 21948365
TI  - Advances in understanding the structure, function, and mechanism of the SCIN and
      Efb families of Staphylococcal immune evasion proteins.
AB  - Our understanding of both the nature and diversity of Staphylococcal immune
      evasion proteins has increased tremendously throughout the last several years.
      Among this group of molecules, members of the SCIN and Efb families of complement
      inhibitors have been the subject of particularly intense study. This work has
      demonstrated that both types of proteins exert their primary function by
      inhibiting C3 convertases, which lie at the heart of the complement-mediated
      immune response. Despite this similarity, however, significant differences in
      structure/function relationships and mechanisms of action exist between these
      bacterial proteins. Furthermore, divergent secondary effects on host immune
      responses have also been described for these two protein families. This chapter
      summarizes recent advances toward understanding the structure, function, and
      mechanism of the SCIN and Efb families, and suggests potential directions for the
      field over the coming years.

PMID- 21948368
TI  - Complement involvement in neovascular ocular diseases.
AB  - Pathological neovascularization (NV) is a hallmark of late stage neovascular age
      related macular degeneration (AMD), diabetic retinopathy (DR), and retinopathy of
      prematurity (ROP). There is accumulating evidence that alterations in
      inflammatory and immune system pathways that arise from genetic differences,
      injury, and disease can predispose individuals to retinal neovascular eye
      diseases. Yet the mechanism of disease progression with respect to the complement
      system in these maladies is not fully understood. Recent studies have implicated
      the complement system as an emerging player in the etiology of several retinal
      diseases. We will summarize herein several of the complement system pathways
      known to be involved in ocular neovascular pathologies. Current treatment for
      many neovascular eye diseases focuses on suppression of NV with laser ablation,
      photodynamic therapy, or anti-VEGF angiogenic inhibitors. However, these
      treatments do not address the underlying cause of many of these diseases. A clear
      understanding of the cellular and molecular mechanisms could bring a major shift
      in our approach to disease treatment and prevention.

PMID- 21948367
TI  - Role of C3, C5 and anaphylatoxin receptors in acute lung injury and in sepsis.
AB  - The complement system plays a major role in innate immune defenses against
      infectious agents, but exaggerated activation of complement can lead to severe
      tissue injury. Systemic (intravascular) activation of complement can, via C5a,
      lead to neutrophil (PMN) activation, sequestration and adhesion to the pulmonary
      capillary endothelium, resulting in damage and necrosis of vascular endothelial
      cells and acute lung injury (ALI). Intrapulmonary (intraalveolar) activation of
      complement can cause ALI that is complement and PMN-dependent, resulting in a
      cytokine/chemokine storm that leads to intense ALI. Surprisingly, C3(-/-) mice
      develop the full intensity of ALI in a C5a-dependent manner due to the action of
      thrombin that generates C5a directly from C5. There is conflicting evidence on
      the role of the second C5a receptor, C5L2 in development of ALI. There is
      accumulating evidence that C5a may suppress inflammatory responses or divert them
      from Th1 to Th2 responses, impacting the innate immune system. Finally, in
      experimental polymicrobial sepsis, there is evidence that many of the adverse
      outcomes can be linked to the roles of C5a and engagement of its two receptors,
      C5aR and C5L2. These observations underscore the diversity of effects of C5a in a
      variety of inflammatory settings.

PMID- 21948369
TI  - Platelets, complement, and contact activation: partners in inflammation and
      thrombosis.
AB  - Platelet activation during thrombotic events is closely associated with
      complement and contact system activation, which in turn leads to inflammation.
      Here we review the interactions between activated platelets and the complement
      and contact activation systems in clotting blood. Chondroitin sulfate A (CS-A),
      released from alpha granules during platelet activation, is a potent mediator of
      crosstalk between platelets and the complement system. CS-A activates complement
      in the fluid phase, generating anaphylatoxins that mediate leukocyte activation.
      No complement activation seems to occur on the activated platelet surface, but C3
      in the form of C3(H(2)O) is bound to the surfaces of activated platelets . This
      finding is consistent with the strong expression of membrane-bound complement
      regulators present at the platelet surface. CS-A exposed on the activated
      platelets is to a certain amount responsible for recruiting soluble regulators to
      the surface. Platelet-bound C3(H(2)O) acts as a ligand for leukocyte CR1 (CD35),
      potentially enabling platelet-leukocyte interactions. In addition, platelet
      activation leads to the activation of contact system enzymes, which are
      specifically inhibited by antithrombin, rather than by C1INH, as is the case when
      contact activation is induced by material surfaces. Thus, in addition to their
      traditional role as initiators of secondary hemostasis, platelets also act as
      mediators and regulators of inflammation in thrombotic events.

PMID- 21948370
TI  - Nuclear factor-kappaB in immunity and inflammation: the Treg and Th17 connection.
AB  - Although nuclear factor-kB (NF-kB) is generally considered to be a pro
      inflammatory transcription factor, recent studies indicate that it also plays a
      critical role in the development of an anti-inflammatory T cell subset called
      regulatory T (Treg) cells. Two NF-kB proteins, c-Rel and p65, drive the
      development of Treg cells by promoting the formation of a Foxp3-specific
      enhanceosome. Consequently, c-Rel-deficient mice have marked reductions in Treg
      cells, and c-Rel-deficient T cells are compromised in Treg cell differentiation.
      However, with the exception of Foxp3, most NF-kB target genes in immune cells are
      pro-inflammatory. These include several Th17-related cytokine genes and the
      retinoid-related orphan receptor-g (Rorg or Rorc) that specifies Th17
      differentiation and lineage-specific function. T cells deficient in c-Rel or p65
      are significantly compromised in Th17 differentiation, and c-Rel -deficient mice
      are defective in Th17 responses. Thus, NF-kB is required for the development of
      both anti-inflammatory Treg and pro-inflammatory Th17 cells.

PMID- 21948371
TI  - Function of Act1 in IL-17 family signaling and autoimmunity.
AB  - The maintenance of immune homeostasis requires the delicate balance between
      response to foreign antigens and tolerance to self. As such, when this balance is
      disrupted, immunodeficiency or autoimmunity may manifest. The adaptor molecule
      known as Act1 is a critical mediator of IL-17 receptor receptor family signaling.
      This chapter will detail the current understanding of Act1 's role in signal
      transduction as well as address the fundamental role of Act1 in autoimmunity. At
      the molecular level Act1 interacts with IL-17 R through the conserved SEFIR
      domain, binds TRAF proteins and exerts E3 ubiquitin ligase activity. In in vivo
      models, Act1 deficiency provides protection against experimental autoimmune
      diseases, such as colitis and EAE. Yet mice lacking in Act1 develop spontaneous
      autoimmune diseases. Indeed, the utility of Act1 seems to rely on the specific
      cell type expression that may determine the pathway that Act1 mediates.

PMID- 21948372
TI  - Differential effect of inhibiting MD-2 and CD14 on LPS- versus whole E. coli
      bacteria-induced cytokine responses in human blood.
AB  - BACKGROUND: Sepsis is a major world-wide medical problem with high morbidity and
      mortality. Gram-negative bacteria are among the most important pathogens of
      sepsis and their LPS content is regarded to be important for the systemic
      inflammatory reaction. The CD14/myeloid differentiation factor 2 (MD-2)/TLR4
      complex plays a major role in the immune response to LPS . The aim of this study
      was to compare the effects of inhibiting MD-2 and CD14 on ultra-pure LPS - versus
      whole E. coli bacteria-induced responses. METHODS: Fresh human whole blood was
      incubated with upLPS or whole E. coli bacteria in the presence of MD-2 or CD14
      neutralizing monoclonal antibodies, or their respective controls, and/or the
      specific complement-inhibitor compstatin. Cytokines were measured by a multiplex
      (n = 27) assay. NFkappaB activity was examined in cells transfected with CD14, MD
      2 and/or Toll-like receptors. RESULTS: LPS-induced cytokine response was
      efficiently and equally abolished by MD-2 and CD14 neutralization. In contrast,
      the response induced by whole E. coli bacteria was only modestly reduced by MD-2
      neutralization, whereas CD14 neutralization was more efficient. Combination with
      compstatin enhanced the effect of MD-2 neutralization slightly. When compstatin
      was combined with CD14 neutralization, however, the response was virtually
      abolished for all cytokines, including IL-17, which was only inhibited by this
      combination. The MD-2-independent effect observed for CD14 could not be explained
      by TLR2 signaling. CONCLUSION: Inhibition of CD14 is more efficient than
      inhibition of MD-2 on whole E. coli-induced cytokine response, suggesting CD14 to
      be a better target for intervention in Gram-negative sepsis, in particular when
      combined with complement inhibition.

PMID- 21948373
TI  - Zebrafish: model for the study of inflammation and the innate immune response to
      infectious diseases.
AB  - The zebrafish (Danio rerio) has been extensively used in biomedical research as a
      model to study vertebrate development and hematopoiesis and recently, it has been
      adopted into varied fields including immunology. After fertilization, larvae
      survive with only the innate immune responses because adaptive immune system is
      morphologically and functionally mature only after 4-6 weeks postfertilization.
      This temporal separation provides a suitable system to study the vertebrate
      innate immune response in vivo, independently from the adaptive immune response.
      The transparency of early life stages allows a useful real-time visualization.
      Adult zebrafish which have complete (innate and adaptative) immune systems offer
      also advantages over other vertebrate infection models: small size, relatively
      rapid life cycle, ease of breeding, and a growing list of molecular tools for the
      study of infectious diseases. In this review, we have tried to give some examples
      of the potential of zebrafish as a valuable model in innate immunity and
      inflammation studies.

PMID- 21948374
TI  - Monocyte-derived inflammatory dendritic cells in the granuloma during
      mycobacterial infection.
AB  - The monocyte-derived, inflammatory dendritic cell subset plays an important role
      during immune responses against infections. This review will focus on the
      complex, changing role of this subset during mycobacterial infection. Studies
      demonstrate that in addition to sustaining a systemic anti-mycobacterial
      response, the inflammatory dendritic cell subset present in Mycobacterium-induced
      granulomas also influences local immune regulation within the granuloma over the
      course of infection. This review will also survey the literature on how similar
      and different inflammatory dendritic cell subsets during other infections.

PMID- 21948375
TI  - NK/DC crosstalk in anti-viral response.
AB  - In recent years, it has been emphasized the role of the crosstalk between natural
      killer (NK) cells and monocyte-derived dendritic cells dendritic cells (moDCs) in
      the regulation of the early phases of innate immunity innate immunity and of the
      subsequent adaptive immune responses. NK cells and DCs coordinate their response
      communicating through direct cell-to-cell contact and soluble factors. NK cells
      appear to contribute to the quality control of immature DCs (iDCs) undergoing
      maturation. On the other hand, DCs may shape the magnitude of innate immune
      responses by modulating the NK-mediated cytolytic activity against tumors or
      infected cells. Recent studies suggest that the cooperation between NK cells and
      DCs is also critical in several anti-viral responses. In particular, NK cells are
      capable of effectively counteracting viral immune evasion immune evasion
      strategies by eliminating infected DCs, that display impaired antigen presenting
      functions, thus indirectly favoring the development of adaptive immune responses
      to viral antigens cross-presented by healthy DCs.

PMID- 21948377
TI  - Nutritional immunity: homology modeling of Nramp metal import.
AB  - The Natural resistance-associated macrophage proteins (Nramp1 and 2) are proton
      dependent solute carriers of divalent metals such as Fe(2+) and Mn(2+) (Slc11a1
      and 2). Their expression in both resting and microbicidal macrophages which
      metabolize iron differently, raises questions about Nramp mechanism of Me(2+)
      transport and its impact in distinct phenotypic contexts. We developed a low
      resolution 3D model for Slc11 based on detailed phylogeny and remote homology
      threading using Escherichia coli Nramp homolog (proton-dependent Mn(2+)
      transporter, MntH) as experimental system. The predicted fold is consistent with
      determinations of transmembrane topology and activity; it indicates Slc11
      carriers are part of the LeuT superfamily. Homology implies that inverted
      structural symmetry facilitates Slc11 H(+)-driven Me(2+) import and provides a 3D
      framework to test structure-activity relationships in macrophages and study
      functional evolution of MntH/Nramp (Slc11) carriers.

PMID- 21948376
TI  - Innate-adaptive crosstalk: how dendritic cells shape immune responses in the CNS.
AB  - Dendritic cells (DCs) are a heterogeneous group of professional antigen
      presenting cells that lie in a nexus between innate and adaptive immunity because
      they recognize and respond to danger signals and subsequently initiate and
      regulate effector T-cell responses. Initially thought to be absent from the CNS,
      both plasmacytoid and conventional DCs as well as DC precursors have recently
      been detected in several CNS compartments where they are seemingly poised for
      responding to injury and pathogens. Additionally, monocyte-derived DCs rapidly
      accumulate in the inflamed CNS where they, along with other DC subsets, may
      function to locally regulate effector T-cells and/or carry antigens to CNS
      draining cervical lymph nodes. In this review we highlight recent research
      showing that (a) distinct inflammatory stimuli differentially recruit DC subsets
      to the CNS; (b) DC recruitment across the blood-brain barrier (BBB) is regulated
      by adhesion molecules, growth factors, and chemokines; and (c) DCs positively or
      negatively regulate immune responses in the CNS.

PMID- 21948378
TI  - Evaluation of species-specific score cutoff values of routinely isolated
      clinically relevant bacteria using a direct smear preparation for matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry-based bacterial
      identification.
AB  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF MS) was introduced a few years ago as a new method for bacterial
      identification. A variety of studies have been published concerning MALDI-TOF MS
      based identification, most of them using culture collections for the validation
      of the respective databases in a retrospective manner in favor of a parallel
      investigation. The score cutoff value is of special importance for reliable
      species identification in the Biotyper database. The score cutoff values
      suggested by the manufacturer have been validated using a previously published
      formic acid extraction protocol. In most of the previously published studies
      investigating the Biotyper database, only little information was given concerning
      species-specific score values. In addition, the mass spectrometer instruments,
      the number of replicates, the number of spectra used to calculate a sum-spectrum
      by the supplied software, and the score cutoff values which have been applied
      varied within these studies. In this study, we compared a straightforward direct
      smear preparation and measurement without replicate testing to defined
      biochemical identifications in a parallel manner. In addition, we described new
      species-specific score cutoff values for the identification of certain bacteria.

PMID- 21948379
TI  - Degradation-induced changes of mechanical properties of an electro-spun polyester
      urethane scaffold for soft tissue regeneration.
AB  - The aim of this study was the in vitro investigation of the change in mechanical
      properties of a fast-degrading electro-spun polymeric scaffold for the use in
      soft tissue regenerative implants. Tubular scaffolds were electro-spun from a
      DegraPol(r) D30 polyesther-urethane solution (target outer diameter: 5.0 mm;
      scaffold wall thickness: 0.99 +/- 0.18 mm). Scaffold samples were subjected to
      hydrolytic in vitro degradation for up to 34 days. The fiber network structure
      and fiber surfaces were inspected on scanning electron micrographs. Following
      vacuum drying and determination of mass, flat samples (9.69 +/- 0.21 * 18.47 +/-
      2.62 mm, n = 5) underwent uni-axial tensile testing (5 load cycles, strain
      epsilon = 0 to 20%; final extension to failure) in circumferential scaffold
      direction after 5, 10, 14, 18, 22, 26, 30, and 34 days of degradation. Scaffold
      mass did not change with degradation. Maximum elastic modulus, maximum stress and
      associated strain were E(max) = 1.14 +/- 0.23 MPa, sigma(max) = 0.52 +/- 0.12 MPa
      and epsilon(max) = 176.8 +/- 21.9% before degradation and E(max) = 0.43 +/- 0.26
      MPa, sigma(max) = 0.033 +/- 0.028 MPa and epsilon(max) = 24.6 +/- 3.0% after 34
      days of degradation. The deterioration of mechanical properties was not reflected
      in the ultrastructural surface morphology of the fibers. The current exploratory
      study provides a basis for the development of constitutive computational models
      of biodegradable scaffolds with future extension of the investigation most
      importantly to capture mechanical effects of regenerating tissue. Future studies
      will include degradation in biological fluids and assessment of molecular weight
      for an advanced understanding of the material changes during degradation.

PMID- 21948380
TI  - Chemistry, science, and our sustainable future.

PMID- 21948381
TI  - Limb oxygenation during the cold pressor test in spinal cord-injured humans.
AB  - OBJECTIVE: To investigate changes in tissue oxygenation in the arm and leg during
      the cold pressor test in humans with spinal cord injury (SCI). METHODS: Subjects
      with SCI at cervical 6 (n=7) and subjects with SCI at thoracic 5 or thoracic 6
      (n=5) experienced 3-min cold water immersion of the foot and subsequent 10-min
      recovery. Changes in tissue oxygenation and blood pressure were determined.
      Tissue oxygenation was assessed by hemoglobin/myoglobin concentration (Hb/MbO2)
      measured using near-infrared spectroscopy. RESULTS: Mean arterial blood pressures
      increased significantly by 15+/-9 and 6+/-6 mmHg during cold water immersion in
      the cervical and thoracic SCI groups, respectively (P<0.001). Hb/MbO2 in the arm
      decreased significantly by 23+/-15 MUM cm during cold water immersion only in the
      cervical SCI group (P<0.001), whereas Hb/MbO2 in the leg decreased significantly
      by 82+/-56 MUM cm during cold water immersion only in the thoracic SCI group
      (P<0.001). INTERPRETATION: Afferent activity coming from below the lesion due to
      cold stimuli would reflexively enhance sympathetic activity in both the arm and
      leg in individuals with cervical SCI but only in the leg in individuals with
      thoracic SCI. A decrease in tissue oxygenation might have been caused by
      sympathetic vasoconstriction. The reduction of tissue oxygenation in the arm was
      marked in individuals with cervical SCI, suggesting differential control of arm
      oxygenation and leg oxygenation in the region below SCI.

PMID- 21948382
TI  - Antiphospholipid antibodies and antithrombin deficiency: double trouble for
      pregnancy.

PMID- 21948383
TI  - Attentional impairment in anxiety: inefficiency in expanding the scope of
      attention.
AB  - BACKGROUND: The ability to attend to relevant visual information in a proficient
      manner is central to most day-to-day tasks. Research suggests, however, that this
      ability is compromised by anxiety such that anxiety results in narrowing the
      focus of visual attention. METHOD: In the current study (N = 58), we used the
      Attention Scope Task [1999: Gerontology 45:102-109] to examine the hypothesis
      that low-anxious individuals would be more proficient than high-anxious
      individuals in their scope of attention, that is, high-anxious individuals would
      have a larger scope of visual attention than low-anxious individuals.
      Additionally, we hypothesized that low-anxious individuals would be more
      proficient than high-anxious individuals in their ability to expand their scope
      of attention. RESULTS: Results revealed that, compared to low-anxious
      individuals, high-anxious individuals were impaired only in their ability to
      expand their scope of attention from a small area to a larger one. Inclusion of a
      depressed control group in the study revealed that our findings are specific to
      the effect of anxiety and not depressive symptoms. CONCLUSION: Thus, high-anxious
      individuals do not appear to have a smaller absolute scope of attention but
      instead seem to have difficulty expanding their attention scope dynamically. We
      discuss our results in relation to cognitive inflexibility in anxiety.

PMID- 21948384
TI  - A semi-mechanistic modeling strategy for characterization of regional absorption
      properties and prospective prediction of plasma concentrations following
      administration of new modified release formulations.
AB  - PURPOSE: To outline and test a new modeling approach for prospective predictions
      of absorption from newly developed modified release formulations based on in vivo
      studies of gastro intestinal (GI) transit, drug release and regional absorption
      for the investigational drug AZD0837. METHODS: This work was a natural extension
      to the companion article "A semi-mechanistic model to link in vitro and in vivo
      drug release for modified release formulations". The drug release model governed
      the amount of substance released in distinct GI regions over time. GI
      distribution of released drug substance, region specific rate and extent of
      absorption and the influence of food intake were estimated. The model was
      informed by magnetic marker monitoring data and data from an intubation study
      with local administration in colon. RESULTS: Distinctly different absorption
      properties were characterized for different GI regions. Bioavailability over the
      gut-wall was estimated to be high in duodenum (70%) compared to the small
      intestine (25%). Colon was primarily characterized by a very slow rate of
      absorption. CONCLUSIONS: The established model was largely successful in
      predicting plasma concentration following administration of three newly developed
      formulations for which no clinical data had been applied during model building.

PMID- 21948385
TI  - Preclinical pharmacokinetics and biodistribution of human papillomavirus DNA
      vaccine delivered in human endogenous retrovirus envelope-coated baculovirus
      vector.
AB  - PURPOSE: Test pharmacokinetics and biodistribution of a human
      papillomavirus(HPV)16L1 DNA vaccine delivered in human endogenous retrovirus
      envelope protein (HERV)-expressing baculovirus (AcHERV) and those of naked
      plasmid vaccine. METHOD: HPV16L1 gene was administrated as a naked plasmid or in
      AcHERV to mice via intravenous and intramuscular routes. HPV16L1 gene was
      extracted and assayed by quantitative real-time polymerase chain reaction, which
      was determined to have a detection limit of 50 copies/ug genomic DNA.. RESULTS:
      Mean residence times of HPV16L1 in AcHERV were 4.8- and 272.2-fold higher than
      naked HPV16L1 DNA vaccines after intramuscular and intravenous administration,
      respectively. Naked HPV16L1 DNA levels 1 month after injection were >3 orders of
      magnitude lower in each tissue tested than AcHERV-delivered HPV16L1, which was
      retained in most tissues without specific tissue tropism. AcHERV-delivered
      HPV16L1 administered intramuscularly persisted at the injection sites. However,
      the levels of copy numbers in muscle were low (1,800/MUg genomic DNA) after 1
      month, and undetectable after 6 months. CONCLUSIONS: HPV16L1 delivered via AcHERV
      resides longer in the body than HPV16L1 in naked form. The lack of tissue tropism
      ensures the safety of AcHERV vectors for further development.

PMID- 21948386
TI  - A new aqueous biphasic system containing polypropylene glycol and a water
      miscible ionic liquid.
AB  - In this work, we proposed a novel aqueous biphasic system (ABS) composed of
      polypropylene glycol P400 (PPG P400) and hydrophilic ionic liquids (IL), 1-alkyl
      3-methylimidazolium bromide (alkyl = ethyl or butyl), forming an upper polymer
      rich phase and a lower IL-rich phase at ambient temperature. This new ABS can
      present interesting characteristics shared by ILs and polymers such as low
      volatility, good solvation ability, tunable physical properties, and high design
      capacity for achieving task-specific phase components to enhance the partitioning
      of target species. Ternary phase diagram of the novel ABS formed by PPG 400 and
      [C(2) mim]Br in water was measured at T = 298.15 K. Factors affecting the binodal
      curves such as the cation side alkyl chain length and the temperature were also
      evaluated. The results were successfully interpreted in terms of the
      kosmotropic/chaotropic nature of ILs. Furthermore, the phase behavior of the PPG
      [C(2) mim]Br ABS is described by the NRTL model. Finally, the extraction
      potential of the proposed ABS was evaluated through its application to the
      extraction of the essential amino acids such as L-tryptophan and L-tyrosine. The
      partition coefficients here obtained demonstrated the fine potential of the
      proposed ABS for biomolecules separation.

PMID- 21948387
TI  - Pregnenolone sulfate activates basic region leucine zipper transcription factors
      in insulinoma cells: role of voltage-gated Ca2+ channels and transient receptor
      potential melastatin 3 channels.
AB  - The neurosteroid pregnenolone sulfate activates a signaling cascade in insulinoma
      cells involving activation of extracellular signal-regulated protein kinase and
      enhanced expression of the transcription factor Egr-1. Here, we show that
      pregnenolone sulfate stimulation leads to a significant elevation of activator
      protein-1 (AP-1) activity in insulinoma cells. Expression of the basic region
      leucine zipper (bZIP) transcription factors c-Jun and c-Fos is up-regulated in
      insulinoma cells and pancreatic beta-cells in primary culture after pregnenolone
      sulfate stimulation. Up-regulation of a chromatin-embedded c-Jun
      promoter/luciferase reporter gene transcription in pregnenolone sulfate
      stimulated insulinoma cells was impaired when the AP-1 binding sites were
      mutated, indicating that these motifs function as pregnenolone sulfate response
      elements. In addition, phosphorylation of cAMP response element (CRE)-binding
      protein is induced and transcription of a CRE-controlled reporter gene is
      stimulated after pregnenolone sulfate treatment, indicating that the CRE
      functions as a pregnenolone sulfate response element as well. Pharmacological and
      genetic experiments revealed that both L-type Ca(2+) channels and transient
      receptor potential melastatin 3 (TRPM3) channels are essential for connecting
      pregnenolone sulfate stimulation with enhanced AP-1 activity and bZIP-mediated
      transcription in insulinoma cells. In contrast, pregnenolone sulfate stimulation
      did not enhance AP-1 activity or c-Jun and c-Fos expression in pituitary
      corticotrophs that express functional L-type Ca(2+) channels but only trace
      amounts of TRPM3. We conclude that expression of L-type Ca(2+) channels is not
      sufficient to activate bZIP-mediated gene transcription by pregnenolone sulfate.
      Rather, additional expression of TRPM3 or depolarization of the cells is required
      to connect pregnenolone sulfate stimulation with enhanced gene transcription.

PMID- 21948388
TI  - Identification of a novel allosteric binding site in the CXCR2 chemokine
      receptor.
AB  - We have shown previously that different chemical classes of small-molecule
      antagonists of the human chemokine CXCR2 receptor interact with distinct binding
      sites of the receptor. Although an intracellular binding site for diarylurea
      CXCR2 antagonists, such as N-(2-bromophenyl)-N'-(7-cyano-1H-benzotriazol-4
      yl)urea (SB265610), and thiazolopyrimidine compounds was recently mapped by
      mutagenesis studies, we now report on an imidazolylpyrimidine antagonist binding
      pocket in the transmembrane domain of CXCR2. Using different CXCR2 orthologs,
      chimeric proteins, site-directed mutagenesis, and in silico modeling, we have
      elucidated the binding mode of this antagonist. Our in silico-guided mutagenesis
      studies indicate that the ligand binding cavity for imidazolylpyrimidine
      compounds in CXCR2 is located between transmembrane (TM) helices 3
      (Phe130(3.36)), 5 (Ser217(5.44), Phe220(5.47)), and 6 (Asn268(6.52),
      Leu271(6.55)) and suggest that these antagonists enter CXCR2 via the TM5-TM6
      interface. It is noteworthy that the same interface is postulated as the ligand
      entry channel in the opsin receptor and is occupied by lipid molecules in the
      recently solved crystal structure of the CXCR4 chemokine receptor, suggesting a
      general ligand entrance mechanism for nonpolar ligands to G protein-coupled
      receptors. The identification of a novel allosteric binding cavity in the TM
      domain of CXCR2, in addition to the previously identified intracellular binding
      site, shows the diversity in ligand recognition mechanisms by this receptor and
      offers new opportunities for the structure-based design of small allosteric
      modulators of CXCR2 in the future.

PMID- 21948389
TI  - Kinetic analysis of lecithin:cholesterol acyltransferase activity toward
      discoidal HDL.
AB  - The kinetics of lecithin:cholesterol acyltransferase(LCAT, EC 2.3.1.43)-catalyzed
      generation of cholesteryl ester in discoidal high density lipoproteins (HDL) was
      analyzed in terms of initial binding of LCAT to the disc surface followed by a
      three-state reaction of the hydrolysis of phosphatidylcholine sn-2 ester bond and
      acyl-enzyme formation. Cholesterol was considered as alcoholic nucleophile that
      increases the solvolysis rate of acyl-LCAT. The raw kinetic data of Sparks et al.
      (J Biol Chem 270:5151-5157, 1995) for four preparations of reconstituted
      discoidal HDL with a constant level of apolipoprotein A-I and
      palmitoyloleoylphosphatidylcholine per disc but with cholesterol in a lipid phase
      continuously increasing from 2.1 to 12.5 mol%, were analyzed in terms of the
      kinetic equation and a complete set of rate constants was obtained. Data at high
      cholesterol content do not indicate a saturation phenomenon, thus giving no
      evidence for a binding of cholesterol to the enzyme. This analysis may be used in
      the study of LCAT activation by exchangeable apolipoproteins and contribution of
      the HDL structure.

PMID- 21948390
TI  - Patterning and development of the atrioventricular canal in zebrafish.
AB  - Proper atrioventricular canal (AVC) patterning and subsequent valvulogenesis is a
      complex process, and defects can result in disease or early death. The zebrafish
      Danio rerio has become a useful model system for studying AVC development, and
      much progress has been made in dissecting out the critical steps. Here, we review
      the recent advances in the field and highlight the cellular and molecular changes
      observed during zebrafish AVC development.

PMID- 21948391
TI  - Analyses of longitudinal, hospital clinical laboratory data with application to
      blood glucose concentrations.
AB  - Electronic medical record (EMR) systems afford researchers with opportunities to
      investigate a broad range of scientific questions. In contrast to purposeful
      study designs, however, EMR data acquisition procedures typically do not align
      with any specific hypothesis. Subsequent investigations therefore require
      detailed characterization of clinical procedures and protocols that underlie EMR
      data, as well as careful consideration of model choice. For example, many
      intensive care units currently implement insulin infusion protocols to better
      control patients' blood glucose levels. The protocols use prior glucose levels to
      determine, in part, how to adjust the infusion rate. Such feedback loops
      introduce time-dependent confounding into longitudinal analyses even though they
      may not always be evident to the analyst. In this paper, we review commonly used
      longitudinal model specifications and interpretations and show how these are
      particularly important in the presence of hospital-based clinical protocols. We
      show that parameter relationships among various models can be used to identify
      and characterize the impact of time-dependent confounding and therefore help
      explain seemingly incongruous conclusions. We also review important estimation
      challenges in the presence of time-dependent confounding and show how certain
      model specifications may be more or less susceptible to bias. To illustrate these
      points, we present a detailed analysis of the relationship between blood glucose
      levels and insulin doses on the basis of data from an intensive care unit.

PMID- 21948392
TI  - Strong cross-talk between angiogenesis and EBV: do we need different treatment
      approaches in lymphoma cases with EBV and/or high angiogenic capacity.
AB  - Angiogenesis is the new blood vessels formation and is the critical event for the
      growth of malignant diseases and plays a key role in the development, invasion,
      and metastasis of malignant tumors. Epstein-Barr virus (EBV) is an important
      carcinogen causing to the some neoplastic disorders and lytically infected cells
      may contribute to the growth of EBV-associated malignancies, and this phenomenon
      is related with enhancing angiogenesis. Due to the strong cross-talk between
      angiogenesis and viral carcinogenesis and increased information about the
      angiogenesis and viral carcinogenesis in lymphomas, we need new therapeutic
      approaches to cases with lymphoma. Due to the strong cross-talk between
      angiogenesis and viral lymphomagenesis, this association was reviewed in this
      study.

PMID- 21948393
TI  - Mantle cell lymphoma successfully treated in a patient with multiple endocrine
      neoplasia type 2: a rare combination of two malignancies.

PMID- 21948394
TI  - Short and long-term outcomes in patients with acute liver failure due to ischemic
      hepatitis.
AB  - AIMS: The purpose of this study is to describe the incidence and presenting
      features of patients with acute liver failure (ALF) due to ischemic hepatitis and
      the prognostic factors associated with short (three-week) and long-term outcomes.
      METHODS: Retrospective cohort analysis of adult patients enrolled in the Acute
      Liver Failure Study Group between 1998 and 2008 with ALF due to ischemic
      hepatitis. Predictors of adverse outcomes three weeks after presentation were
      identified by univariate and multivariate analysis. RESULTS: Ischemic hepatitis
      accounted for 51 (4.4%) of the 1147 ALF patients enrolled. Mean age was 50 years,
      63% were female, and only 31% had known heart disease before presentation.
      However, a cardiopulmonary precipitant of hepatic ischemia was identified in 69%.
      Three-week spontaneous survival was 71%, two patients (4%) underwent liver
      transplantation, and the remaining 13 patients (25%) died of multi-organ failure.
      Adverse outcomes were more frequent in subjects with higher admission phosphate
      levels (HR 1.3, 95% CI 1.1-1.6, P = 0.008) and in subjects with grade 3/4
      encephalopathy at presentation (HR: 8.4, 95% CI 1.1-66.5, P = 0.04). Nineteen of
      the 28 short-term survivors (68%) were still alive at a median follow-up of 3.7
      years whereas nine (32%) others had died at a median follow-up of 2 months.
      CONCLUSIONS: A higher admission serum phosphate level and more advanced
      encephalopathy are associated with a lower likelihood of short-term survival of
      hospitalized patients with ALF due to ischemic hepatitis. Long-term outcomes are
      largely determined by underlying cardiovascular morbidity and mortality.

PMID- 21948395
TI  - Putatively noncoding transcripts show extensive association with ribosomes.
AB  - There have been recent surprising reports that whole genes can evolve de novo
      from noncoding sequences. This would be extraordinary if the noncoding sequences
      were random with respect to amino acid identity. However, if the noncoding
      sequences were previously translated at low rates, with the most strongly
      deleterious cryptic polypeptides purged by selection, then de novo gene
      origination would be more plausible. Here we analyze Saccharomyces cerevisiae
      data on noncoding transcripts found in association with ribosomes. We find many
      such transcripts. Although their average ribosomal densities are lower than those
      of protein-coding genes, a significant proportion of noncoding transcripts
      nevertheless have ribosomal densities comparable to those of coding genes. Most
      show increased ribosomal association in response to starvation, as has been
      previously reported for other noncoding sequences such as untranslated regions
      and introns. In rich media, ribosomal association is correlated with start codons
      but is not usually consistent and contiguous beyond that, suggesting that
      translation occurs only at low rates. One transcript contains a 28-codon open
      reading frame, which we name RDT1, which shows evidence of translation, and may
      be a new protein-coding gene that originated de novo from noncoding sequence. But
      the bulk of the ribosomal association cannot be attributed to unannotated protein
      coding genes. Our primary finding of extensive ribosome association shows that a
      necessary precondition for selective purging is met, making de novo gene
      evolution more plausible. Our analysis is also proof of principle of the utility
      of ribosomal profiling data for the purpose of gene annotation.

PMID- 21948397
TI  - Electrophoretic deposition of bioactive silica-calcium phosphate nanocomposite on
      Ti-6Al-4V orthopedic implant.
AB  - Bioactive silica-calcium phosphate nanocomposite (SCPC) has been coated on Ti-6Al
      4V implant employing an electrophoretic deposition (EPD) technique. The effects
      of composition and pH of the suspending medium on the zeta potential of three
      different SCPC formulations; SCPC25, SCPC50 and SCPC75 were analyzed. The average
      zeta potential of SCPC50 in pure ethanol was more negative than that of SCPC25 or
      SCPC75; however, the difference was not statistically significant. Discs of Ti
      6Al-4V were passivated, coated with SCPC50 (200 nm-10 MUm) and thermally treated
      at 600-800 degrees C to produce a coating thickness in the range of 43.1 +/- 5.7
      to 30.1 +/- 4.6 MUm. After treatment at 600, 700, and 800 degrees C, the adhesion
      strength at the SCPC50/Ti-6Al-4V interface was 42.6 +/- 3.6, 44.7 +/- 8.7, and
      47.2 +/- 4.3 MPa, respectively. SEM-EDX analyses of SCPC50-coated Ti-6Al-4V
      preimmersed in PBS for 7 days showed the formation of a Ca-deficient
      hydroxyapatite surface layer. ICP-OES analyses of the immersing solution (n = 6)
      showed an increase in the ionic concentration of Si from 3.3 +/- 0.9 to 5.0 +/-
      1.2 ppm between days 1 and 4; after which no significant change in the Si
      concentration was measured. Bone marrow mesenchymal stem cells attached to the
      SCPC50-coated implants expressed significantly higher (p < 0.05) alkaline
      phosphatase activity (82.4 +/- 25.6 nmoles p-NP/mg protein/min) than that
      expressed by cells attached to HA-coated or uncoated implants. Results of the
      study suggest that bioactive SCPC50 can efficiently be coated on Ti-6Al-4V using
      EPD. The SCPC50 coating has the potential to enhance bone integration with the
      orthopedic implant.

PMID- 21948396
TI  - Abundant degenerate miniature inverted-repeat transposable elements in genomes of
      epichloid fungal endophytes of grasses.
AB  - Miniature inverted-repeat transposable elements (MITEs) are abundant repeat
      elements in plant and animal genomes; however, there are few analyses of these
      elements in fungal genomes. Analysis of the draft genome sequence of the fungal
      endophyte Epichloe festucae revealed 13 MITE families that make up almost 1% of
      the E. festucae genome, and relics of putative autonomous parent elements were
      identified for three families. Sequence and DNA hybridization analyses suggest
      that at least some of the MITEs identified in the study were active early in the
      evolution of Epichloe but are not found in closely related genera. Analysis of
      MITE integration sites showed that these elements have a moderate integration
      site preference for 5' genic regions of the E. festucae genome and are
      particularly enriched near genes for secondary metabolism. Copies of the EFT
      3m/Toru element appear to have mediated recombination events that may have
      abolished synthesis of two fungal alkaloids in different epichloae. This work
      provides insight into the potential impact of MITEs on epichloae evolution and
      provides a foundation for analysis in other fungal genomes.

PMID- 21948398
TI  - Morphology of resin-dentin interfaces after Er,Cr:YSGG laser and acid etching
      preparation and application of different bonding systems.
AB  - The goal of this study was to show the modifications in the ultrastructure of the
      dentin surface morphology following different surface treatments. The stability
      of the adhesive compound with dentin after laser preparation compared with
      conventional preparation using different bonding agents was evaluated. An
      Er,Cr:YSGG laser and 36% phosphoric acid in combination with various bonding
      systems were used. A total of 100 caries-free human third molars were used in
      this study. Immediately after surgical removal teeth were cut using a band saw
      and 1-mm thick dentin slices were created starting at a distance of 4 mm from the
      cusp plane to ensure complete removal of the enamel. The discs were polished with
      silicon carbide paper into rectangular shapes to a size of 6 * 4 mm (+/-0,2
      mm).The discs as well as the remaining teeth stumps were stored in 0.9% NaCl at
      room temperature. The specimens were divided into three main groups (group I
      laser group, group II etch group, group III laser and etch group) and each group
      was subdivided into three subgroups which were allocated to the different bonding
      systems (subgroup A Excite, subgroup B Scotchbond, subgroup C Syntac). Each disc
      and the corresponding tooth stump were treated in the same way. After preparation
      the bonding composite material was applied according to the manufacturers'
      guidelines in a hollow tube of 2 mm diameter to the disc as well as to the
      corresponding tooth stump. Shear bond strength testing and environmental scanning
      electron microscopy were used to assess the morphology and stability of the resin
      dentin interface. The self-etching bonding system showed the highest and the most
      constant shear values in all three main groups, thus enabling etching with
      phosphoric acid after laser preparation to be avoided. Thus we conclude that
      laser preparation creates a surface texture that allows prediction of the quality
      of the restoration without the risk of negative influences during the following
      treatment steps. This can easily and repeatedly be achieved.

PMID- 21948399
TI  - In vitro effects of Er,Cr:YSGG laser on dentine hypersensitivity. Dentine
      permeability and scanning electron microscopy analysis.
AB  - The aim of the present study was to determine clinical parameters for the use of
      Er,Cr:YSGG laser in the treatment of dentine hypersensitivity. Two antagonist
      areas were determined as control and experimental areas for irradiation in 90
      premolar roots. Each surface was conditioned with 24% EDTA (sub-group 1) and 35%
      phosphoric acid (sub-group 2) and irradiated with the following settings: 1)
      Er:YAG, 60 mJ, 2 Hz, defocused; groups 2 to 9: irradiation with Er,Cr:YSGG laser,
      20 Hz, Z6 tip, 0% of air and water: 2) Er,Cr:YSGG 0.25 W; 3) 0.5 W; 4) 0.75 W; 5)
      1.0 W; 6) 1.25 W, 7) 1.50 W, 8) 2 W; 9) 2 W. After irradiation, samples were
      immersed in methylene blue solution and included in epoxy resin to obtain
      longitudinal cuts. The images were digitalized and analyzed by computer software.
      Although the samples irradiated with Er:YAG laser showed less microleakage, sub
      group 1 showed differences between the groups, differing statistically from
      groups 3, 6, and 9. The results of sub-group 2 showed that the mean values of
      Er:YAG samples showed a negative trend, however, no differences were detected
      between the groups. For scanning electron microscopy analysis, dentine squares
      were obtained and prepared to evaluate the superficial morphology. Partial
      closure of dentinal tubules was observed after irradiation with Er:YAG and
      Er,Cr:YSGG laser in the 0.25 and 0.50 W protocols. As the energy densities rose,
      open dentinal tubules, carbonization and cracks were observed. It can be
      concluded that none of the parameters were capable of eliminating microleakage,
      however, clinical studies with Er:YAG and Er,Cr:YSGG lasers should be conducted
      with the lowest protocols in order to determine the most satisfactory setting for
      dentine hypersensitivity.

PMID- 21948402
TI  - MALDI-TOF serum profiling using semiautomated serum peptide capture with magnetic
      reversed phase (C18) beads.
AB  - Mass spectrometry can be used to generate diagnostic peptide peak profiles
      "signatures" of serum samples. Peak profiles can be used to compare different
      sera and correlate samples (i.e., patient groups) with clinical data to assist in
      diagnosis, monitoring, and/or prediction. We describe the semiautomated capture
      of serum peptides/small proteins with magnetic beads that harbor C18 alkyl
      chains, the deposition of captured material on a target plate for MALDI-TOF mass
      spectrometry, as well as, general guidelines for data acquisition. We also
      include, in a separate note, a short manual version of the capture procedure.
      Overall, the serum sample processing protocol, reported here, is reproducible and
      robust. In conjunction with MALDI-TOF mass spectrometry, this protocol allows for
      the profiling of several hundreds of serum peptides.

PMID- 21948400
TI  - Antiinflammatory effect of low-level laser therapy on Staphylococcus epidermidis
      endophthalmitis in rabbits.
AB  - A rabbit model of endophthalmitis was established to evaluate the
      antiinflammatory effect of low-level laser therapy (LLLT) as an adjunct to
      treatment for Staphylococcus epidermidis endophthalmitis. Rabbits were randomly
      divided into three groups to receive intravitreal injections into their left eye:
      group A received 0.5 mg vancomycin (100 MUl), group B received 0.5 mg vancomycin
      + 0.2 mg dexamethasone (100 MUl), and group C received 0.5 mg vancomycin (100
      MUl) and continuous wave semiconductor laser irradiation (10 mW, lambda = 632 nm)
      focused on the pupil. Slit lamp examination and B-mode ultrasonography were
      conducted to evaluate the symptoms of endophthalmitis. Polymorphonuclear cells
      and tumour necrosis factor alpha (TNF-alpha) in aqueous fluid were measured at 0
      h, and 1, 2, 3, 7 and 15 days. A histology test was conducted at 15 days. B-mode
      ultrasonography and histology revealed that groups B and C had less inflammation
      than group A at 15 days. Groups B and C had fewer polymorphonuclear cells and
      lower levels of TNF-alpha in aqueous fluid than group A at 2, 3 and 7 days (P <
      0.05). There was no significant difference between groups B and C (P > 0.05).
      There was no significant difference between groups A, B and C at 15 days (P >
      0.05). As an adjunct to vancomycin therapy to treat S. epidermidis
      endophthalmitis, LLLT has an antiinflammatory effect similar to that of
      dexamethasone.

PMID- 21948403
TI  - Proteomics of epithelial lining fluid obtained by bronchoscopic microprobe
      sampling.
AB  - Epithelial lining fluid (ELF) forms a thin fluid layer that covers the mucosa of
      the alveoli, the small airways, and the large airways. Since it constitutes the
      first barrier between the lung and the outer world, it is an interesting target
      for proteomics studies that focus on lung disease. Bronchoscopic microprobe (BMP)
      sampling of ELF uses small probes with an absorptive tip that are introduced
      bronchoscopically. In contrast to other methods used so far for the collection of
      biofluids from the lung (e.g., bronchoalveolar lavage fluid, induced sputum),
      this technique has the advantage that ELF is not diluted and contains high
      concentrations of biomolecules. In addition, the investigated location in the
      tracheobronchial tree is well defined, and there is no contamination with
      oropharyngeal bacteria or saliva. Despite occasional blood contamination of the
      probes by scratching the mucosa of the airways, the proteomic analysis of
      microprobe-sampled ELF opens new possibilities for research in lung diseases. Our
      work focuses particularly on the induction and progression of cigarette smoke
      induced Chronic Obstructive Pulmonary Disease (COPD). In this chapter, we
      describe the practical aspects of sampling ELF followed by a detailed description
      of proteomics analysis by LC-MS/MS after protein separation by SDS-PAGE and in
      gel digestion. As an example, we apply this proteomic platform to the
      identification and quantification of proteins in ELF from COPD patients and
      healthy subjects.

PMID- 21948404
TI  - Protein identification using nano-HPLC-MS: ESI-MS and MALDI-MS interfaces.
AB  - Body fluids and body tissues have a myriad of peptides and proteins that, very
      often, the traditional methodologies of proteomics, such as conventional gel
      electrophoresis or mass spectrometry, are unable to characterize. We describe two
      protocols to characterize high molecular weight peptides (>3 kDa) and intact
      proteins involving on-line trypsin digestion, separation of the digests by nano
      HPLC, and analysis by mass spectrometry using two different ionization sources
      (matrix-assisted laser desorption and electrospray ionization). These protocols
      have the advantage of promoting protein denaturation in an aqueous-organic
      solvent, which reduces the derivatization of the sample and facilitates an in
      depth analysis for detection and identification of proteins. Additional
      advantages include the following: (1) integration of these protocols into
      standard proteomic workflows after the preprocessing of samples and separation;
      (2) use of high-resolution monolithic columns; and (3) the ability to acquire
      information from minimal amounts of sample.

PMID- 21948405
TI  - Three-dimensional peptide fractionation for highly sensitive nanoscale LC-based
      shotgun proteomic analysis of complex protein mixtures.
AB  - To sensitively analyze complex protein mixtures by mass spectrometry-based
      shotgun proteomics, researchers have employed platforms that couple orthogonal
      peptide fractionation methods using nanoscale HPLC. Commonly used platforms have
      coupled either strong cation exchange (SCX) HPLC or preparative isoelectric
      focusing (IEF) with nanoscale reversed-phase (nanoRP) HPLC fractionation of
      peptides. Coupling two dimensions of peptide fractionation, prior to mass
      spectrometric analysis, increases the sensitivity for identifying low abundance
      proteins. However, the large dynamic range of protein abundance and high level of
      complexity of protein mixtures derived from many biological sources, such as
      bodily fluids, require additional steps of peptide fractionation. To address this
      shortcoming, we have developed a platform combining three dimensions of peptide
      fractionation as follows: (1) preparative IEF; (2) SCX HPLC; and (3) nanoRP HPLC.
      This platform significantly increases the sensitivity of shotgun proteomic
      analysis in complex protein mixtures. Here, we describe the implementation of
      this three-dimensional peptide fractionation platform for proteomic studies of
      complex mixtures.

PMID- 21948406
TI  - Nanospray ion mobility mass spectrometry of selected high mass species.
AB  - The introduction of electrospray ionization (ESI) and in particular nano
      electrospray (nESI) has enabled the routine mass spectrometric (MS) analysis of
      large protein complexes in native aqueous buffers. Time-of-flight (ToF) mass
      spectrometers, in particular the hybrid quadrupole time-of-flight (Q-ToF)
      instruments, are well suited to the analysis of large protein complexes. When
      ionized under native-MS conditions, protein complexes routinely exhibit multiple
      charge states in excess of m/z 6,000, well above the standard mass range of many
      quadrupole or ion cyclotron-based instruments. The research area of native MS has
      expanded considerably in the last decade and has shown particular relevance in
      the area of protein structure determination. Researchers are now able to
      routinely measure intact MS spectra of protein complexes above 1 MDa in mass. The
      advent of ion mobility mass spectrometry (IM-MS), in combination with molecular
      dynamics (MD) studies, is now allowing researchers to infer the shape of the
      protein complex being analyzed. Herein, we describe how to acquire IM-MS data
      that ranges from inorganic salt clusters of caesium iodide (CsI) to large
      biomolecular complexes such as the chaperone protein GroEL.

PMID- 21948407
TI  - Nanoelectrospray-MS( n ) of native and permethylated glycans.
AB  - The profound biological relevance of protein and lipid glycosylation has made
      glycomics (i.e., the comprehensive study of all glycans in a cell or organism),
      an indispensable field of research in the life sciences. Consequently, numerous
      strategies have been developed for a high-throughput analysis of complex glycan
      mixtures, with mass spectrometry (MS) playing a key role. In particular,
      nanoelectrospray ionization (ESI-) MS( n ), employing multiple cycles of
      isolation and fragmentation of native or derivatized precursor ions, is
      recognized as a highly valuable tool in this context, as it allows, at least in
      part, structural characterization of glycans without prior fractionation. This
      chapter describes suitable work flows for this purpose and illustrates both
      advantages and limitations for this type of analysis. Furthermore, the use of
      newly developed software tools for data handling is outlined.

PMID- 21948408
TI  - N-linked global glycan profiling by nanoLC mass spectrometry.
AB  - A method is detailed for the global profiling of underivatized N-linked glycans
      that are derived from complex protein mixtures. The method consists of five main
      steps that include the following: (1) protein denaturation; (2) enzymatic
      digestion; (3) solid phase extraction; (4) nanoLC MS analysis; and (5) data
      interpretation. Materials, methods, and algorithms for the identification of both
      glycan composition and structure are summarized. In addition, potential problems
      and their resolutions are addressed.

PMID- 21948409
TI  - Applications of nanoscale liquid chromatography coupled to Tandem mass
      spectrometry in quantitative studies of protein expression, protein-protein
      interaction, and protein phosphorylation.
AB  - Mass spectrometry can provide a very sensitive and rapid analysis of protein
      expression and can be used as an alternative to immunochemical methods to study
      protein-protein interaction and protein posttranslational modifications. In many
      circumstances, a functional study, such as one that aims to elucidate a specific
      signaling pathway or disease state, will require the detection and quantification
      of a specific set of proteins and their modifications. Very often, there will be
      no available antibody for some of the proteins in the set, and mass spectrometry
      will be the only option. This chapter describes a robust and efficient protocol
      for a small-scale sample preparation and a suite of separation and mass
      spectrometry techniques that allow the quantitative analysis of low femtomolar
      amounts of proteins that may be obtained from very limited amount of clinical
      specimens, affinity techniques, and cell sorting. The protocols can be used by
      researchers in the applied biomedical field and also in basic cell biology.

PMID- 21948410
TI  - Nano LC-MS/MS: a robust setup for proteomic analysis.
AB  - Nanoscale liquid chromatography coupled to tandem mass spectrometry (nano LC
      MS/MS) has become an essential tool in the field of proteomics. In fact, its
      sensitivity has advantages over conventional LC-MS/MS that allow the analysis of
      peptide mixtures in sample-limited situations (e.g., proteolytically digested
      proteins isolated by two-dimensional gel electrophoresis). Technical challenges,
      associated with low flow rates of the chromatographic separation, make this
      technology still difficult to run routinely. Here, we describe a nano LC-MS/MS
      setup that allows several weeks of continuous operation for the analysis of
      peptides derived by enzymatic digestion of either purified proteins or moderately
      complex protein mixtures.

PMID- 21948411
TI  - Nanofluidic devices for rapid continuous-flow bioseparation.
AB  - Compared with conventional gel-based techniques, such as gel electrophoresis,
      which are routinely used for bioseparation in biology and biomedical
      laboratories, nanofluidic devices with regular engineered sieving structures
      offer the potential for faster separation, better resolution, higher throughput,
      and more convenient sample recovery. Here, we detail the fabrication process of a
      two-dimensional nanofluidic filter array device and its implementation for rapid
      continuous-flow separation of biomolecules such as proteins.

PMID- 21948412
TI  - Quantifying attomole amounts of proteins from complex samples by nano-LC and
      selected reaction monitoring.
AB  - Selected reaction monitoring (SRM) is one of the most powerful techniques for the
      relative and absolute quantification of proteins from complex protein mixtures.
      In contrast to traditional protein quantification methods such as ELISAs or RIAs,
      the SRM method uses mass spectrometry for detection. Further benefits of SRM are
      as follows: (1) high specificity and sensitivity; (2) large linear dynamic range
      of at least three orders of magnitude; and (3) the possibility to quantify
      multiple proteins simultaneously in a single MS run from an individual sample. To
      perform SRM-based protein quantification reliably, a careful design of the assay
      is essential, and several pitfalls must be avoided. The aim of this chapter is to
      help SRM newcomers to establish SRM-based protein quantification assays and
      discuss an overview of typical work flows that are applied during SRM assay
      development.

PMID- 21948413
TI  - A sample preparation method for gold nanoparticle-assisted laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - A sample preparation method to detect small molecules in laser
      desorption/ionization time-of-flight mass spectrometry (LDI-TOF MS) was developed
      using bare gold nanoparticles (AuNPs) as matrices. In this sample preparation
      method, the analyte is deposited first and then followed by the bare AuNPs.
      Neutral steroids and carbohydrates, which are difficult to ionize, using organic
      matrices, are cationized efficiently by combining AuNP-assisted LDI-TOF MS with
      this sample preparation method. As compared to the dried-droplet method (i.e.,
      analyte and bare AuNPs are mixed and dried together), this method offers distinct
      advantages for improving shot-to-shot reproducibility, increasing the ionization
      efficiency of the analyte, and reducing sample preparation time.

PMID- 21948414
TI  - Nanostructured TiO2 thin films for phosphoproteomics studies with MALDI mass
      spectrometry.
AB  - Alterations in protein phosphorylation, a posttranslational modification (PTM)
      that regulates many -processes in living cells, is a fundamental mechanism of
      many diseases, including cancer. Phosphoproteomics, with the combined use of
      affinity chromatography and electrospray ionization (ESI) or matrix-assisted
      laser desorption/ionization (MALDI) mass spectrometry, is shedding light into
      phosphorylation signaling pathways at the proteome level and helps to solve
      difficulties related to sample complexity and phosphopeptide enrichment. One of
      the most frequent and efficient methods used to enrich samples for the
      phosphorylated components is titanium dioxide chromatography. Titanium dioxide
      has a high affinity for phosphopeptides and can also be selective in specific
      experimental conditions. Here, we describe a protocol for the use of a MALDI
      plate covered with titanium dioxide nanostructured film, a device developed for a
      rapid and efficient study of phosphorylated peptides.

PMID- 21948415
TI  - Nanofilament silicon for matrix-free laser desorption/ionization mass
      spectrometry.
AB  - Mass spectrometry (MS) provides quantitative information toward accurate mass
      identification of unknown molecules and has become a powerful and widely used
      technique for bioanalysis. In this chapter, we describe the fabrication and MS
      analysis steps for a high sensitivity matrix-free laser desorption/ionization
      mass spectrometry (LDI-MS) target substrate termed nanofilament silicon (nSi).
      Unlike other nanostructured porous silicon surfaces, nSi possesses an open pore
      morphology with associated benefits including efficient transport of sample into
      the nanopores and effective removal of solvent from the surface. The utility of
      nSi targets for LDI-MS analysis lies primarily in the analysis of small
      molecules, which are typically less than 5,000 Da with a detection sensitivity in
      the attomole range.

PMID- 21948416
TI  - Protein nanoarrays for high-resolution patterning of bacteria on gold surfaces.
AB  - In recent years, the majority of research on surface patterning, as a means of
      precisely controlling cell -positioning and adhesion on surfaces, has focused on
      eukaryotic cells. Such research has led to new insights into cell biology,
      advances in tissue engineering, and cell motility. In contrast, considerably less
      work has been reported on tightly controlled patterning of bacteria, despite its
      potential in a wide variety of applications, including fabrication of in vitro
      model systems for studies of bacterial processes, such as quorum sensing and
      horizontal gene transfer. This is partly due to their small size - often 1-3 MUm
      or less. To study these processes, microscale and nanoscale engineered material
      surfaces must be developed to create in vitro bacteria arrays, which can allow
      valuable insights into natural systems such as the soil or the human gut, and are
      often complex and spatially structured habitats. Here, we outline a protocol to
      create defined patterns of bacteria to study such systems at the single cell
      level that is based on the formation of protein nanoarrays on mannoside
      terminated self-assembled monolayers via nanocontact printing and the subsequent
      deposition of bacteria from solution on the unpatterned regions of the mannoside
      terminated substrate.

PMID- 21948417
TI  - Engineered multifunctional nanotools for biological applications.
AB  - Smart multifunctional magnetic nanoparticles are popular candidates for several
      biological applications owing to their intrinsic magnetic property and diverse
      applications that range from rare protein separation and biomedical utilization
      to cancer therapy and diagnostics. A universal protocol, for the development of
      such nanocarriers, is highly desirable for scientists with different backgrounds
      so that custom-made multifunctional nanoparticles can be developed to address
      their needs, among which are the superparamagnetic iron oxide and manganese oxide
      nanoparticles that are synthesized through high temperature decomposition
      reactions. However, an interface is needed to present these inorganic materials
      to biomolecules to enhance their application for different biological use. This
      compatibility is achieved by introducing a class of multifunctional copolymers.
      Magnetic nanoparticles are elaborately decorated with copolymers that carry three
      principle functionalities as follows: (1) dopamine moieties for surface anchorage
      of metal oxides; (2) dyes for optical detection; and (3) a large variety of
      functional molecules such as amines or carboxylates for conjugation of various
      biomolecules (i.e., proteins, nucleic acids, enzymes, etc.). These copolymers, in
      combination with nanoparticles, serve as a tool box that results in engineered
      nanotools with customized modifications and functionalities for applications in
      fields ranging from proteomics -bioseparation to tumor therapy.

PMID- 21948418
TI  - Selective capture of phosphopeptides by zirconium phosphonate-magnetic
      nanoparticles.
AB  - Immobilized metal affinity chromatography is a widely used method for the
      enrichment of phosphopeptides from proteolytic digests prior to mass
      spectrometric analysis. Here, we describe the selective enrichment of
      phosphopeptides from tryptic digests of proteins (alpha- and beta-caseins) by
      zirconium phosphonate-magnetic Fe(3)O(4)/SiO(2) (core/shell) nanoparticles for
      phosphoproteome analysis with MALDI-TOF mass spectrometry.

PMID- 21948419
TI  - Nanowire biosensors for label-free, real-time, ultrasensitive protein detection.
AB  - Sensitive and quantitative analysis of proteins is central to disease diagnosis,
      drug screening, and proteomic studies. Among recent research advances exploiting
      new nanomaterials for biomolecule analysis, silicon nanowires (SiNWs), which are
      configured as field-effect transistors (FETs), have emerged as one of the most
      promising and powerful platforms for label-free, real-time, and highly sensitive
      electrical detection of proteins as well as many other biological species. Here,
      we describe a detailed protocol for realizing SiNW biosensors for protein
      detection that includes SiNW synthesis, FET device fabrication, surface receptor
      functionalization, and electrical sensing measurements. Moreover, incorporating
      both p-type and n-type SiNWs in the same sensor array provides a unique means of
      internal control for sensing signal verification.

PMID- 21948420
TI  - Generation of anti-infectome/anti-proteome nanobodies.
AB  - The immunization of an animal with a whole proteome or the infection of an animal
      and the screening of the resulting antibody repertoire on either the same or
      different proteome(s) or the infecting agent(s), omits the laborious steps of
      recombinant protein expression and purification to obtain multiple antigen
      binders. This procedure allows the identification of antibodies that are specific
      to unique or common signatures of different proteomes without prior knowledge of
      these signatures.Nanobodies are the smallest (15 kDa, 2.2 nm diameter, 4 nm
      height) in vivo affinity-matured functional antigen-binding entities that are
      derived from camelid heavy-chain antibodies. Due to their small size, recognition
      of unique epitopes, high affinity, and easy tailoring, nanobodies are attractive
      affinity reagents for various applications, including diagnosis and therapy.We
      detail a protocol to generate, isolate, express, and purify anti-infectome/anti
      proteome nanobodies.

PMID- 21948421
TI  - Isolation, propagation, and analysis of biological nanoparticles.
AB  - Calcifying biologic nanoparticles (NPs) have been implicated as nucleation points
      for a number of -pathologic events that include vascular calcification and the
      formation of kidney stones. In order to study these potential relationships,
      reproducible isolation of well-characterized biologic NPs is a necessity. Our
      group has isolated and propagated calcifying NPs from several human tissues and
      renal stones. Specific proteins that could nucleate a calcium phosphate shell
      under physiologic conditions have been identified as part of their structure,
      including elongation factor Tu (EF-Tu) and fetuin-A. Visualization, using
      advanced transmission electron microscopy (TEM), immunofluorescence microscopy,
      and nuclear and antibody staining in conjunction with flow cytometry, can further
      elucidate NPs composition and their role in pathology. In order to allow uniform
      investigation by others, the isolation, culture, and handling procedures for
      biologic NPs from human calcified vascular tissue and kidney stones are reported
      in detail.

PMID- 21948422
TI  - Functionalized soluble nanopolymers for phosphoproteome analysis.
AB  - Protein phosphorylation plays a critical role in the regulation of many cellular
      functions. Phosphoproteomic analyses facilitate an in-depth understanding of such
      phosphorylation-dependent signaling networks. The use of mass spectrometry in
      phosphoproteomics has been especially successful, but the approach largely
      depends on an efficient method to enrich phosphopeptides from complex mixtures.
      We have developed a novel, effective soluble nanopolymer-based phosphopeptide
      enrichment technique, termed PolyMAC (polymer-based metal ion affinity capture).
      The homogenous, hyperfunctional nature of PolyMAC reagent makes it a more
      competent choice for highly efficient phosphopeptide binding and isolation, which
      was demonstrated through several applications with simple protein mixture and
      complex cell extract.

PMID- 21948423
TI  - Elucidating structural dynamics of integral membrane proteins on native cell
      surface by hydroxyl radical footprinting and nano LC-MS/MS.
AB  - Although the snapshots of different in vitro conformational states have been
      intensively studied, current techniques such as nuclear magnetic resonance, X-ray
      crystallography, and electron microscope method cannot probe the in vivo
      conformational movements of integral membrane proteins on cell surfaces. Here, we
      describe a hydroxyl radical protein footprinting coupled to a mass spectrometry
      detection technique to probe the structural dynamics of a membrane protein
      directly on the native cell surface. This method uses in situ generation of
      hydroxyl radicals to oxidize and covalently modify integral membrane proteins on
      the cell surface. To explain this technique in detail, we use the porin OmpF as
      an example, although the method may be applied to study any membrane protein.
      Footprinting results show that the surface mapping data of OmpF are consistent
      with its current crystallographic structure. In addition, this technique also
      enables the detection of in vivo voltage gating of porin OmpF for the first time.
      This novel cell surface footprinting method coupled with MS analysis can be a
      potentially efficient method to study the structural dynamics of the membrane
      proteins of a living cell.

PMID- 21948424
TI  - Application of electrostatic repulsion hydrophilic interaction chromatography to
      the characterization of proteome, glycoproteome, and phosphoproteome using nano
      LC-MS/MS.
AB  - In shotgun proteomics, peptide fractionation is essential for in-depth
      characterization of proteomes and the mapping of protein posttranslational
      modifications. Recently, a mix-mode chromatography [i.e., electrostatic repulsion
      hydrophilic interaction chromatography (ERLIC)] has been developed and found to
      be a versatile method in proteome characterization. Here, we use ERLIC to
      characterize the glycoproteome and phosphoproteome simultaneously. We also
      demonstrate that the ERLIC can be an alternative to the commonly used strong
      cation exchange chromatography for higher recovery of proteins during whole
      proteome analysis. These protocols can be easily adopted in most proteomics
      laboratories.

PMID- 21948428
TI  - Oxygen defects and novel transport mechanisms in apatite ionic conductors:
      combined 17O NMR and modeling studies.

PMID- 21948425
TI  - Rare hemoglobinopathy presenting as progressive dyspnea.

PMID- 21948429
TI  - Strong binding of hydrocarbons to cucurbituril probed by fluorescent dye
      displacement: a supramolecular gas-sensing ensemble.

PMID- 21948430
TI  - Tumor-targeting gold particles for dual computed tomography/optical cancer
      imaging.

PMID- 21948431
TI  - Sr3[Co(CN)3] and Ba3[Co(CN)3]: crystal structure, chemical bonding, and
      conceptional considerations of highly reduced metalates.

PMID- 21948432
TI  - Supramolecular nanofibers and hydrogels of nucleopeptides.

PMID- 21948433
TI  - Computationally guided stereocontrol of the combined C-H functionalization/Cope
      rearrangement.

PMID- 21948434
TI  - A polymerization-powered motor.

PMID- 21948435
TI  - Bioorthogonal probes for polo-like kinase 1 imaging and quantification.

PMID- 21948436
TI  - Efficient and stereoselective synthesis of alpha(2->9) oligosialic acids: from
      monomers to dodecamers.

PMID- 21948437
TI  - Remarkably high reactivity of Pd(OAc)2/pyridine catalysts: nondirected C-H
      oxygenation of arenes.

PMID- 21948438
TI  - Activated phenacenes from phenylenes by nickel-catalyzed alkyne cycloadditions.

PMID- 21948439
TI  - A bioinspired Ugi/Michael/aza-Michael cascade reaction in aqueous media: natural
      product-like molecular diversity.

PMID- 21948440
TI  - Carboxylic acids as traceless directing groups for formal meta-selective direct
      arylation.

PMID- 21948441
TI  - Nitrogen insertion into a corrole ring: iridium monoazaporphyrins.

PMID- 21948442
TI  - A highly active and reusable self-assembled poly(imidazole/palladium) catalyst:
      allylic arylation/alkenylation.

PMID- 21948443
TI  - The long-arm effect: influence of axially chiral phosphoramidite ligands on the
      diastereo- and enantioselectivity of the tandem 1,4-addition/fluorination.

PMID- 21948444
TI  - Short, enantioselective total syntheses of (-)-8-demethoxyrunanine and (-)
      cepharatines A, C, and D.

PMID- 21948445
TI  - Oxo group protonation and silylation of pentavalent uranyl Pacman complexes.

PMID- 21948446
TI  - Stereoselective alkylation of allylic alcohols: tandem ethylation and
      functionalization.

PMID- 21948447
TI  - Asymmetric organocatalysis and analysis on a single microfluidic nanospray chip.

PMID- 21948448
TI  - The role of dissociative electron attachment in focused electron beam induced
      processing: a case study on cobalt tricarbonyl nitrosyl.

PMID- 21948449
TI  - Enantioselective metal-free diamination of styrenes.

PMID- 21948450
TI  - Photolyase-like repair of psoralen-crosslinked nucleic acids.

PMID- 21948451
TI  - Increasing alphavbeta3 selectivity of the anti-angiogenic drug cilengitide by N
      methylation.

PMID- 21948452
TI  - Detection of DNA-ligand binding oscillations by Stokes-shift measurements.

PMID- 21948454
TI  - A review of orthostatic blood pressure regulation and its association with mood
      and cognition.
AB  - AIMS: This paper will review literature that examines the psychological and
      neuropsychological correlates of orthostatic blood pressure regulation. RESULTS:
      The pattern of change in systolic blood pressure in response to the shift from
      supine to upright posture reflects the adequacy of orthostatic regulation.
      Orthostatic integrity involves the skeletal muscle pump, neurovascular
      compensation, neurohumoral effects and cerebral flow regulation. Various
      physiological states and disease conditions may disrupt these mechanisms.
      Clinical and subclinical orthostatic hypotension has been associated with
      impaired cognitive function, decreased effort, reduced motivation and increased
      hopelessness as well as dementia, diabetes mellitus, and Parkinson's disease.
      Furthermore, inadequate blood pressure regulation in response to orthostasis has
      been linked to increased depression and anxiety as well as to intergenerational
      behavioral sequalae. CONCLUSIONS: Identifying possible causes and consequences of
      subclinical and clinical OH are critical in improving quality of life for both
      children and older adults.

PMID- 21948455
TI  - Discrimination between silicone oil droplets and protein aggregates in
      biopharmaceuticals: a novel multiparametric image filter for sub-visible
      particles in microflow imaging analysis.
AB  - PURPOSE: Accurate monitoring of the sub-visible particle load in protein
      biopharmaceuticals is increasingly important to drug development. Manufacturers
      are expected to characterize and control sub-visible protein particles in their
      products due to their potential immunogenicity. Light obscuration, the most
      commonly used analytical tool to count microscopic particles, does not allow
      discrimination between potentially harmful protein aggregates and harmless
      pharmaceutical components, e.g. silicone oil, commonly present in drug products.
      Microscopic image analysis in flow-microscopy techniques allows not only
      counting, but also classification of sub-visible particles based on morphology.
      We present a novel approach to define software filters for analysis of particle
      morphology in flow-microscopic images enhancing the capabilities of flow
      microscopy. METHODS: Image morphology analysis was applied to analyze flow
      microscopy data from experimental test sets of protein aggregates and silicone
      oil suspensions. RESULTS: A combination of four image morphology parameters was
      found to provide a reliable basis for automatic distinction between silicone oil
      droplets and protein aggregates in protein biopharmaceuticals resulting in low
      misclassification errors. CONCLUSIONS: A novel, custom-made software filter for
      discrimination between proteinaceous particles and silicone oil droplets in flow
      microscopy imaging analysis was successfully developed.

PMID- 21948456
TI  - Opposite effects of polyols on antibody aggregation: thermal versus mechanical
      stresses.
AB  - PURPOSE: To investigate the physical stability of antibody-polyol formulations
      under thermal and mechanical stresses. METHODS: mAb-U was analyzed in buffer,
      trehalose, sucrose, glycerol and ethylene glycol solutions at pH 7.0. T(m1) of
      mAb-U was determined using DSC. Thermal stress studies were performed by
      incubating mAb-U-polyol solutions at 40 degrees C (2 months), 50 degrees C (3
      weeks) and 65 degrees C (5 days). Mechanical stress studies were conducted by
      shaking mAb-U-polyol solutions at 200 rpm for 5 days at 25 degrees C. RESULTS:
      Trehalose and glycerol increased the T(m1) of mAb-U, whereas ethylene glycol
      decreased it. The trend observed in the order of increasing aggregation of mAb-U
      after thermal stress (40 degrees C and 50 degrees C) was buffer = trehalose =
      sucrose<glycerol<ethylene glycol. A similar trend in aggregation was observed for
      65 degrees C studies. An inverse relationship was observed in aggregation trends
      upon exposure to mechanical and thermal stresses. CONCLUSIONS: Preferentially
      excluded polyols increase the conformational stability of proteins but also
      increase their chemical potential in the solution phase. This increase in free
      energy can promote precipitation and interfacial adsorption of a protein as these
      reactions result in a decrease in its free energy. Therefore, addition of polyols
      can be destabilizing for the physical stability of aqueous protein formulations.

PMID- 21948457
TI  - A semi-mechanistic modeling strategy to link in vitro and in vivo drug release
      for modified release formulations.
AB  - PURPOSE: To develop a semi-mechanistic model linking in vitro to in vivo drug
      release. METHODS: A nonlinear mixed-effects model describing the in vitro drug
      release for 6 hydrophilic matrix based modified release formulations across
      different experimental conditions (pH, rotation speed and ionic strength) was
      developed. It was applied to in vivo observations of drug release and tablet
      gastro intestinal (GI) position assessed with magnetic marker monitoring (MMM).
      By combining the MMM observations with literature information on pH and ionic
      strength along the GI tract, the mechanical stress in different parts of the GI
      tract could be estimated in units equivalent to rotation speed in the in vitro
      USP 2 apparatus. RESULTS: The mechanical stress in the upper and lower stomach
      was estimated to 94 and 134 rpm, respectively. For the small intestine and colon
      the estimates of mechanical stress was 93 and 38 rpm. Predictions of in vivo drug
      release including between subject/tablet variability was made for other newly
      developed formulations based on the drug release model and a model describing
      tablet GI transit. CONCLUSION: The paper outlines a modeling approach for
      predicting in vivo behavior from standard in vitro experiments and support
      formulation development and quality control.

PMID- 21948458
TI  - Condensational growth of combination drug-excipient submicrometer particles for
      targeted high efficiency pulmonary delivery: comparison of CFD predictions with
      experimental results.
AB  - PURPOSE: The objective of this study was to investigate the hygroscopic growth of
      combination drug and excipient submicrometer aerosols for respiratory drug
      delivery using in vitro experiments and a newly developed computational fluid
      dynamics (CFD) model. METHODS: Submicrometer combination drug and excipient
      particles were generated experimentally using both the capillary aerosol
      generator and the Respimat inhaler. Aerosol hygroscopic growth was evaluated in
      vitro and with CFD in a coiled tube geometry designed to provide residence times
      and thermodynamic conditions consistent with the airways. RESULTS: The in vitro
      results and CFD predictions both indicated that the initially submicrometer
      particles increased in mean size to a range of 1.6-2.5 MUm for the 50:50
      combination of a non-hygroscopic drug (budesonide) and different hygroscopic
      excipients. CFD results matched the in vitro predictions to within 10% and
      highlighted gradual and steady size increase of the droplets, which will be
      effective for minimizing extrathoracic deposition and producing deposition deep
      within the respiratory tract. CONCLUSIONS: Enhanced excipient growth (EEG)
      appears to provide an effective technique to increase pharmaceutical aerosol
      size, and the developed CFD model will provide a powerful design tool for
      optimizing this technique to produce high efficiency pulmonary delivery.

PMID- 21948459
TI  - Persistent impact of illness on families of adult survivors of childhood central
      nervous system tumors: a population-based cohort study.
AB  - OBJECTIVE: This study aims to determine the long-term impact on families of adult
      survivors of childhood central nervous system tumors. Illness-related family
      consequences were studied in relation to modifying determinants. METHODS: In a
      population-based cohort of parents of 697 survivors 18 years and older, 551
      parents provided data. The impact of cancer on the families was evaluated in four
      domains using the Impact on Family Scale (economic situation, personal burden,
      social life, sibling impact). The results were analyzed in relation to survivors'
      health assessed using the Health Utilities IndexTM, parent satisfaction with
      information about illness and treatment, and perceived health-care needs of their
      child. RESULTS: Despite an established mild-to-moderate impact on the group
      level, outcomes provided evidence of substantial cancer-related family
      consequences even once the child had reached adulthood. About one fifth of
      parents reported psychological and financial difficulties exceeding the cutoff
      limit for a significant impact still >= 5 years after diagnosis. A stronger total
      family impact was associated with poorer health of survivors (F[3,302] = 56.65, p
      < 0.001), and unmet informational - (F[3,231] = 14.06, p < 0.001) and health-care
      needs (t(218) = 5.31, p < 0.001). The impact was unrelated to survivors' age at
      follow-up and time since diagnosis. CONCLUSIONS: Adverse cancer-related
      consequences affect a considerable portion of families of childhood survivors of
      central nervous system tumor, even after reaching adulthood. The impact is
      aggravated by lasting sequelae and perceived shortcomings of long-term follow-up,
      factors that partly are avoidable. Improved clinical follow-up should
      particularly address illness information and long-term health-care needs to
      reduce the impact on families of survivors suffering from chronic health
      conditions.

PMID- 21948461
TI  - Thymidylate synthase expression is closely associated with outcome in patients
      with pulmonary adenocarcinoma.
AB  - The aim of this study is to elucidate the prognostic significance of thymidylate
      synthase (TS), orotate phosphoribosyltransferase (OPRT) and dihydropyrimidine
      dehydrogenase (DPD) in completely resected non-small cell lung cancer (NSCLC).
      One hundred and sixty patients with NSCLC were included in this study. Tumor
      sections were stained by immunohistochemistry for TS, OPRT, DPD, glucose
      transporter 1 (Glut1), hypoxia inducible factor-1alpha (HIF-1alpha), vascular
      endothelial growth factor (VEGF), microvessel density (MVD) determinated by CD34,
      epidermal growth factor receptor (EGFR), phosph-Akt, phosph-mammalian target of
      rapamycin (mTOR) and p53. TS, OPRT and DPD were positively expressed in 46, 71
      and 54%, respectively. The expression of TS and OPRT was significantly higher in
      patients with non-adenocarcinoma (non-AC) (n = 53) than adenocarcinoma (AC) (n =
      107), and DPD expression was higher in adenocarcinoma as compared with non
      adenocarcinoma. A positive TS expression was an independent prognostic factor for
      predicting a poor outcome in patients with AC, but not in those with non-AC. In
      AC patients, TS expression was significantly associated with advanced stage,
      lymph node metastases, vascular invasion, Glut1, HIF-1alpha, angiogenesis, EGFR
      signaling pathway and p53. In patients with non-AC, TS expression was not closely
      correlated with outcome and these biomarkers. A positive TS expression was a
      powerful prognostic factor to predict a poor outcome in completely resected AC
      patients.

PMID- 21948460
TI  - Origin and Functions of Tumor-Associated Myeloid Cells (TAMCs).
AB  - The construction of an inflammatory microenvironment provides the fuel for cancer
      development and progression. Hence, solid tumors promote the expansion and the
      recruitment of leukocyte populations, among which tumor-associated myeloid cells
      (TAMCs) represent a paradigm for cancer-promoting inflammation. TAMCs group
      heterogeneous phagocytic populations stemming from a common myeloid progenitor
      (CMP), that orchestrate various aspects of cancer, including: diversion and
      skewing of adaptive responses; immunosuppression; cell growth; angiogenesis;
      matrix deposition and remodelling; construction of a metastatic niche and actual
      metastasis. Several evidence indicate that TAMCs show plasticity and/or
      functional heterogeneity, suggesting that tumour-derived factors promote their
      functional "reprogramming" towards protumoral activities. While recent studies
      have attempted to address the role of microenvironment signals, the interplay
      between cancer cells, innate and adaptive immunity is now emerging as a crucial
      step of the TAMCs reprogramming. Here we discuss the evidence for the
      differentiation of TAMCs during the course of tumor progression and the molecular
      mechanisms that regulate such event.

PMID- 21948462
TI  - Allowing for missing outcome data and incomplete uptake of randomised
      interventions, with application to an Internet-based alcohol trial.
AB  - Missing outcome data and incomplete uptake of randomised interventions are common
      problems, which complicate the analysis and interpretation of randomised
      controlled trials, and are rarely addressed well in practice. To promote the
      implementation of recent methodological developments, we describe sequences of
      randomisation-based analyses that can be used to explore both issues. We
      illustrate these in an Internet-based trial evaluating the use of a new
      interactive website for those seeking help to reduce their alcohol consumption,
      in which the primary outcome was available for less than half of the participants
      and uptake of the intervention was limited. For missing outcome data, we first
      employ data on intermediate outcomes and intervention use to make a missing at
      random assumption more plausible, with analyses based on general estimating
      equations, mixed models and multiple imputation. We then use data on the ease of
      obtaining outcome data and sensitivity analyses to explore departures from the
      missing at random assumption. For incomplete uptake of randomised interventions,
      we estimate structural mean models by using instrumental variable methods. In the
      alcohol trial, there is no evidence of benefit unless rather extreme assumptions
      are made about the missing data nor an important benefit in more extensive users
      of the intervention. These findings considerably aid the interpretation of the
      trial's results. More generally, the analyses proposed are applicable to many
      trials with missing outcome data or incomplete intervention uptake. To facilitate
      use by others, Stata code is provided for all methods.

PMID- 21948463
TI  - Identification of novel and selective Kv2 channel inhibitors.
AB  - Identification of selective ion channel inhibitors represents a critical step for
      understanding the physiological role that these proteins play in native systems.
      In particular, voltage-gated potassium (K(V)2) channels are widely expressed in
      tissues such as central nervous system, pancreas, and smooth muscle, but their
      particular contributions to cell function are not well understood. Although
      potent and selective peptide inhibitors of K(V)2 channels have been
      characterized, selective small molecule K(V)2 inhibitors have not been reported.
      For this purpose, high-throughput automated electrophysiology (IonWorks Quattro;
      Molecular Devices, Sunnyvale, CA) was used to screen a 200,000-compound mixture
      (10 compounds per sample) library for inhibitors of K(V)2.1 channels. After
      deconvolution of 190 active samples, two compounds (A1 and B1) were identified
      that potently inhibit K(V)2.1 and the other member of the K(V)2 family, K(V)2.2
      (IC(50), 0.1-0.2 MUM), and that possess good selectivity over K(V)1.2 (IC(50) >10
      MUM). Modeling studies suggest that these compounds possess a similar three
      dimensional conformation. Compounds A1 and B1 are >10-fold selective over Na(V)
      channels and other K(V) channels and display weak activity (5-9 MUM) on Ca(V)
      channels. The biological activity of compound A1 on native K(V)2 channels was
      confirmed in electrophysiological recordings of rat insulinoma cells, which are
      known to express K(V)2 channels. Medicinal chemistry efforts revealed a defined
      structure-activity relationship and led to the identification of two compounds
      (RY785 and RY796) without significant Ca(V) channel activity. Taken together,
      these newly identified channel inhibitors represent important tools for the study
      of K(V)2 channels in biological systems.

PMID- 21948465
TI  - Oncolytic herpes simplex virus engineering and preparation.
AB  - Herpes simplex virus-1 (HSV-1) is an enveloped, double-stranded DNA virus that
      has been used with modification as an oncolytic virus against a number of tumor
      types. Modifications that make HSV-1 replication--conditional, i.e., selectively
      divide in replicating cells make it fulfill a prerequisite criteria for oncolytic
      viruses. Other appealing features of HSV-1 as an oncolytic virus include its
      large, modifiable genome; its sensitivity to antiviral agents, such as
      ganciclovir; and its lack of host cell integration. Here, we review the methods
      of HSV-1 engineering, through traditional recombination techniques as well as
      through bacterial artificial chromosome (BAC) technology. We then describe
      protocols for titering, amplification, and purification of engineered HSV-1
      derived oncolytic viruses.

PMID- 21948464
TI  - Radiotherapy for prolactin-secreting pituitary tumors.
AB  - Review the medical and surgical management of patients with prolactinomas and
      provide an in-depth appraisal of the role of radiotherapy in the treatment of
      prolactinomas. A thorough review of the pertinent literature was carried out and
      relevant topics were identified. Topics covered in this comprehensive review
      include: indications for the use of radiotherapy, choice between conventional
      radiotherapy and stereotactic radiosurgery, as well as the benefits and potential
      complications associated with each modality. Due to the excellent response rates
      with medical management, and rapid symptom relief afforded by resection or
      debulking surgery in patients who do not respond or tolerate medical therapy,
      radiotherapy is reserved for patients who do not respond to dopamine agonists and
      surgery. Both external beam radiotherapy and stereotactic radiosurgery retain
      important roles in the treatment of refractory or recurrent prolactinomas.
      Choosing the optimal approach is crucial in maximizing tumor control outcomes and
      minimizing the risks associated with treatment. The primary determinants of
      optimal radiation approach are proximity of the tumor to the optic apparatus and
      tumor size, with radiosurgery being our recommended treatment of choice unless
      the tumor is larger than 3-4 cm or within 3 mm of the optic nerves, chiasm or
      tracts. Optimal multidisciplinary management requires the identification of
      appropriate candidates for radiotherapy in order to take full advantage of
      treatment options available for each patient.

PMID- 21948466
TI  - Construction of capsid-modified adenoviruses by recombination in yeast and
      purification by iodixanol-gradient.
AB  - Adenovirus represents a valuable tool for the treatment of cancer, but tumor
      targeting remains a pending issue. Most common procedures to modify adenovirus
      genome are time-consuming due to the requirement of multiple cloning steps, and
      the low efficacy of the recombination process. Here, we present a new method for
      homologous recombination in yeast to fast construct recombinant adenoviruses.
      Also, an alternative procedure to purify viral stocks, based on iodixanol
      gradient is described. Compared to classical methods, iodixanol is nontoxic to
      cells, which avoids desalting to use in vitro and in vivo. Moreover, viral stocks
      are more viable and it can be used for large-scale purifications. Finally, a
      protocol for analyzing blood persistence of modified vector in in vivo
      biodistribution is presented.

PMID- 21948467
TI  - Construction of targeted and armed oncolytic adenoviruses.
AB  - Oncolytic (replication-competent) adenoviruses (Ads) represent the most advanced
      platform for cancer gene therapy. These viral vectors ablate tumors by killing
      tumor cells in the process of virus replication. As progeny virions are released,
      they infect remaining cancer cells, generating a bystander effect. Ads engineered
      for increased cancer specificity produce less damage to normal tissues. First
      generation oncolytic Ads have demonstrated acceptable levels of safety while the
      efficacy was observed only in combination with chemotherapy and/or radiation.
      Second-generation oncolytic Ads are armed with therapeutic transgenes to increase
      release, spread, and bystander effect for enhancing the efficacy. Third
      generation oncolytic Ads are armed vectors with capsid modifications for
      transductional detargeting from normal tissues and targeting to cancer cells.
      Chemical modification of the capsid additionally improves therapeutic window.
      Here, we describe methods for generation and characterization of advanced
      generation oncolytic Ads.

PMID- 21948468
TI  - Syrian hamster tumor model to study oncolytic Ad5-based vectors.
AB  - Oncolytic (replicating) adenovirus (Ad) vectors are emerging as a promising form
      of a cancer therapy agent. There has been a need for an appropriate animal model
      to study oncolytic Ad since human Ad -replication is usually species specific. We
      have shown that Syrian (golden) hamsters are an appropriate animal model to study
      human Ad5-based vectors. Syrian hamsters are immunocompetent, and they allow
      human Ad5 replication in normal tissues as well as in Syrian hamster cancer
      cells. The development of the Syrian hamster as a model to study oncolytic Ad
      vectors has opened avenues to explore the role of host immune response and
      preexisting immunity in Ad vector efficacy and toxicity/biodistribution following
      Ad vector administration. Since most of the normal tissues in the Syrian hamster
      are permissive for human Ad5 replication, Ad vectors can be studied in the
      context of orthotopic cancer model developed in Syrian hamsters.

PMID- 21948469
TI  - Adenoviral gene expression and replication in human tumor explant models.
AB  - Promising results have been reported from numerous studies with replication
      selective oncolytic adenoviral mutants as novel treatments for a variety of
      cancers. Most of these studies were performed in cancer cell lines, dissociated
      tumor tissue, or animal models, and the predictive utility for efficacy and
      safety in the clinical setting is unclear. Indeed, the outcome of many clinical
      trials with viral mutants that demonstrated high efficacy preclinically has so
      far been disappointing, necessitating better test models. To this end, we
      developed a methodology using primary human cancer specimens for evaluation of
      cytotoxicity ex vivo including colorectal liver metastasis, ovarian, breast,
      colon, and prostate carcinomas. Under optimized culture conditions, primary human
      tumor tissue remained viable for up to 48 h, enabling evaluation of viral mutants
      in tissue with intact morphology. This assay may have great utility to
      investigate novel viral mutants and to identify treatment sensitive cancers by
      assessing specific oncolytic mutants in individual cases.

PMID- 21948470
TI  - Imaging luciferase-expressing viruses.
AB  - Optical imaging of luciferage gene expression has become a powerful tool to track
      cells and viruses in vivo in small animal models. Luciferase imaging has been
      used to study the location of infection by replication-defective and replication
      competent viruses and to track changes in the distribution of viruses in mouse
      models. This approach has also been used in oncolytic studies as a noninvasive
      means to monitor the growth and killing of tumor cells modified with luciferase
      genes. In this chapter, we describe the techniques used for luciferase imaging as
      have been applied to track replication-defective and replication-competent
      adenoviruses in mouse and hamster models of oncolysis and virus pharmacology.
      Although these methods are simple, the process of obtaining accurate luciferase
      imaging data has many caveats that are discussed.

PMID- 21948471
TI  - In vivo positron emission tomography imaging using the sodium iodide symporter as
      a reporter gene.
AB  - Information regarding the biodistribution and kinetics of spread of oncolytic
      viruses is crucial for safety considerations in the design of future, more
      efficient reagents. Although optical imaging can be used to gain this information
      in rodent models, imaging with radioactive isotopes presents the advantage of
      being directly applicable to humans, and preclinical imaging data can provide a
      basis for the design of clinical protocols. In this chapter, we describe the use
      of the Na/I symporter as a reporter gene, associated with (124)I-NaI as a
      radiotracer, to monitor the anatomical localization, as well as the propagation,
      of oncolytic viruses using dedicated, preclinical positron emission tomography
      scanners.

PMID- 21948472
TI  - Maintaining and loading neural stem cells for delivery of oncolytic adenovirus to
      brain tumors.
AB  - Despite recent advancements in the treatment of cancer, the prognosis for
      patients with malignant brain tumors remains poor. The success of currently
      available therapies has been limited in part because of the disseminated nature
      of these tumors. Furthermore, most of these tumors, when in a high-grade form,
      are resistant to chemo- and radiotherapy. Taking the above considerations into
      account, effective treatment of these cancers not only requires the development
      of new means to target tumor burdens that have dispersed significantly from their
      site of origin, but also therapeutic approaches which can appropriately
      discriminate between tumor cell and normal brain. In the past two decades, novel
      approaches involving the use of oncolytic adenoviruses to target -malignant brain
      tumors have undergone extensive investigation and proven to be an effective mode
      of antiglioma therapy. While the use of various oncolytic adenoviruses has been
      proven to be safe for local delivery in preclinical and clinical trials, the
      successful application of this approach in the clinic has been hampered by the
      host immune response against the viral vector. The discovery of the inherent
      tumor-tropic properties of neural stem cells (NSCs) provides a unique opportunity
      that employs NSCs as a cellular vehicle to track tumor cells and deliver
      therapeutic oncolytic virus. This presents a novel platform for targeted delivery
      of oncolytic adenovirus to disseminated tumors selectively while hiding the
      therapeutic virus from the host immune system. NSC loaded with an oncolytic
      adenovirus offer a more selective and effective method of targeting satellite
      tumor burdens and this chapter reviews the methodology associated with this
      unique approach.

PMID- 21948473
TI  - Targeting brain tumor stem cells with oncolytic adenoviruses.
AB  - In 2004, brain tumor stem cells (BTSCs) were isolated from surgical human
      malignant gliomas. This cancer cell population has been identified as the root
      for tumor initiation and resistance to therapies. Thus, it is imperative to
      develop new therapies that can eradicate this subpopulation to improve the
      prognosis of patients with brain tumors. Our group previously reported the
      antiglioma effect of the tumor-selective oncolytic adenovirus Delta-24-RGD that
      is now being tested in a phase I clinical trial for patients with malignant
      gliomas. We also showed that Delta-24-RGD infects, replicates in, and induces
      cell death in BTSCs. Interestingly, we observed that adenoviral-infected cells
      undergo autophagy and that autophagy-related cytoplasmic vacuolization might be
      part of the lysis process. Here, we summarize the materials and methods used in
      our study as follows: establishment of neurosphere cultures from surgical samples
      of human glioblastoma multiformes; assessment of stem cell markers; examination
      of adenoviral receptors in BTSCs; evaluation of the cytotoxicity induced by
      oncolytic adenoviruses; and assessment of autophagy in oncolytic adenovirus
      infected BTSCs in vitro, and finally we describe a method to detect upregulation
      of the autophagy-related protein Atg5 in tumors treated with Delta-24-RGD.

PMID- 21948474
TI  - Propagation, purification, and in vivo testing of oncolytic vesicular stomatitis
      virus strains.
AB  - Oncolytic viruses are self-amplifying therapeutics that specifically replicate in
      and kill cancer cells. We have previously shown that vesicular stomatitis virus
      (VSV) can be used as an oncolytic virus. A strain of VSV harboring a mutation in
      the M protein (VSVDelta51) was found to exhibit enhanced tumor selectivity over
      its wild-type counterpart due to its inability to overcome antiviral programs in
      normal cells and due to the frequent defects in antiviral signaling pathways
      observed in the majority of tumors. VSVDelta51 can harbor transgenes, is easily
      propagated and purified to high titers, and shows potent oncolytic activity in
      several mouse models, including syngeneic CT26-lacZ subcutaneous colon carcinoma
      models. However, VSV-neutralizing antibodies targeting mainly the VSV-G surface
      glycoprotein arise within 3-5 days following the initial dose. This should be
      considered for strategies aiming at increasing the effectiveness of VSV through
      delivery of additional doses of virus or aiming to prolong VSV replication in
      vivo.

PMID- 21948475
TI  - Oncolytic measles virus retargeting by ligand display.
AB  - Despite significant advances in recent years, treatment of metastatic
      malignancies remains a significant challenge. There is an urgent need for
      development of novel therapeutic approaches. Virotherapy approaches have
      considerable potential, and among them measles virus (MV) vaccine strains have
      emerged as a promising oncolytic platform. Retargeted MV strains deriving from
      the Edmonston vaccine lineage (MV-Edm) have shown comparable antitumor efficacy
      to unmodified strains against receptor expressing tumor cells with improved
      therapeutic index. Here, we describe the construction, rescue, amplification, and
      titration of fully retargeted MV-Edm derivatives displaying tumor specific
      receptor binding ligands on the viral surface in combination with H protein CD46
      and SLAM entry ablating mutations.

PMID- 21948476
TI  - Exploring host factors that impact reovirus replication, dissemination, and
      reovirus-induced cell death in cancer versus normal cells in culture.
AB  - Oncolytic viruses, such as reovirus, offer a promising approach to cancer
      treatment. Concurrently, oncolytic viruses provide a valuable tool for
      deciphering unique attributes of cancer cells that support superior virus
      replication, cell death, or virus dissemination. Through our studies on various
      cancer cell lines, as well as isogenic cells with and without transformation by
      oncogenic Ras, we have identified at least four steps of virus replication that
      can be augmented in transformed cells. Ras transformation can support efficient
      reovirus uncoating during entry, production of progeny with high infectious
      capacity, and reovirus-induced apoptosis. Furthermore, Ras transformation also
      precludes interferon production following reovirus infection, permitting enhanced
      cell-to-cell virus spread. Methods that measure the efficiency of reovirus
      replication and dissemination described in this chapter can be used in
      combination with assorted cell culture systems to better understand the host
      factors that regulate reovirus oncolysis.

PMID- 21948477
TI  - Analysis of three properties of Newcastle disease virus for fighting cancer:
      tumor-selective replication, antitumor cytotoxicity, and immunostimulation.
AB  - Newcastle disease virus (NDV), a bird paramyxovirus, is an antitumor agent which
      has shown benefits to cancer patients. Its antineoplastic efficacy appears to be
      associated with three properties of the virus: 1. Selective replication in tumor
      cells. This feature can be studied at the RNA level, for example by RT-PCR, and
      at the protein level by immunochemistry. 2. Oncolytic properties (of some
      strains). The use of cultures of tumor cell lines represents a selective model to
      study direct viral oncolysis at the cellular level. The capacity of NDV to lyse
      tumor cells can be analyzed in vitro using cytotoxic assays based on the WST1
      chemical reagent. The endoplasmic reticulum stress, which is induced by infection
      with the oncolytic NDV strain MTH-68/H and which plays an important role in the
      viral oncolytic effects, can be analyzed by Western blotting using specific
      monoclonal antibodies. Such stress appears as a key component of NDV
      cytotoxicity. 3. Immunostimulatory capacity. We describe an in vitro test called
      "Tumor Neutralisation Assay" which allows the analysis of bystander antitumor
      immune effects induced in human peripheral blood mononuclear cells by NDV. There
      are two variants, one for oncolytic NDV strains and the other one for nonlytic
      NDV strains. NDV may use several mechanisms to exert its tumor-killing action:
      direct cytotoxicity against cancer cells but also nonspecific as well as active
      specific antitumor immune responses from the host organism. All the methods
      described here allow to evaluate the different oncolytic and immunostimulatory
      capacities of various strains of NDV. They are crucial to harness optimal
      antitumor activity by appropriate combinations of virus strains and application
      regimens.

PMID- 21948478
TI  - Next-generation oncolytic vaccinia vectors.
AB  - Oncolytic vaccinia viruses have made some impressive advances over the last 5
      years, with a range of -different backbones displaying significant antitumor
      responses in preclinical models, and some exciting clinical results being
      reported against liver cancers. Because the virus is capable of rapid spread
      within the tumor, has evolved to spread relatively undetected within the blood
      stream, does not integrate into the host cell chromosome, and can infect almost
      any cell type, it is well-suited to the requirements for a successful oncolytic.
      In addition, the extensive clinical use of this virus means that
      contraindications to its use are known, and approved and experimental antivirals
      are available. Furthermore, because the virus has a large array of virulence
      genes whose deletion may target different properties of the cancer cell, and a
      large cloning capacity allowing for insertion of multiple transgenes, the
      possibilities for further development of novel and next-generation oncolytic
      vectors are multitude.

PMID- 21948479
TI  - Evaluation of innate immune signaling pathways in transformed cells.
AB  - Oncolytic viruses, the use of viruses to treat cancer, is emerging as a new
      option for cancer therapy. Oncolytic viruses, of both DNA and RNA origin, exhibit
      the ability to preferentially replicate in and kill cancer cells plausibly due to
      defects in innate immune signaling or translation regulation that are acquired
      during cellular transformation. Here, we review concepts and assays that describe
      how to analyze signaling pathways that govern the regulation of Type I IFN
      production as well as the induction of interferon-stimulated antiviral genes,
      events that are critical for mounting an effective antiviral response. The
      following procedures can be used to assess whether innate immune pathways that
      control antiviral host defense are defective in tumor cells - mechanisms that may
      help to explain viral oncolysis.

PMID- 21948480
TI  - Time-dependent density functional theory for calculating origin-independent
      optical rotation and rotatory strength tensors.
AB  - An approach to calculate origin-independent electronic chiroptical property
      tensors using time-dependent density functional theory (TDDFT) and gauge
      including atomic orbital (GIAO) basis sets is evaluated. Computations of origin
      dependent optical rotation tensors and of rotatory strengths needed to simulate
      circular dichroism spectra are presented. The optical rotation tensor
      computations employ solutions of coupled perturbed Kohn-Sham equations for a
      dynamic electric field and a static magnetic field. Because the magnetic field is
      time independent, the GIAO treatment is somewhat simplified compared to a
      previously reported method, at some added computational cost if hybrid
      functionals are employed. GIAO rotatory strengths are also calculated, using
      transition density matrices from a standard TDDFT excitation energy module. A new
      implementation in the NWChem quantum chemistry package is employed for
      representative computations of origin-invariant chiroptical response tensors for
      methyloxirane, norbornenone, and the ketosteroid androstadienone. For the steroid
      molecule the vibrational structure of the CD spectrum is modeled explicitly by
      using calculated Franck-Condon factors. The agreement with experiment is
      favorable.

PMID- 21948482
TI  - Delayed perforation occurring after endoscopic submucosal dissection for early
      gastric cancer.
AB  - Delayed perforation occurring after endoscopic submucosal dissection (ESD) is a
      rare but serious complication which sometimes requires emergent surgery. However,
      reports of its characteristics, including endoscopic imaging and management, are
      not fully detailed. A 70-year-old woman was referred to our hospital for the
      treatment of early gastric cancer. On the day of the ESD, hematemesis was
      observed because of a Mallory-Weiss tear, and a visible vessel in the post-ESD
      ulcer was additionally treated endoscopically by coagulation. Second-look
      endoscopic examination on the next day revealed a perforation 3 mm in diameter at
      the treated vessel in the ulcer. The shape of the perforation was round and the
      color of the surrounding muscle layer had become whitish. The perforation was
      closed with endoclips, and decompression of the pneumoperitoneum was performed.
      The patient was conservatively managed and was discharged 13 days after the ESD.
      We show endoscopic images of delayed perforation and discuss the mechanism and
      management of this complication.

PMID- 21948481
TI  - Isorhamnetin inhibits H2O2-induced activation of the intrinsic apoptotic pathway
      in H9c2 cardiomyocytes through scavenging reactive oxygen species and ERK
      inactivation.
AB  - As a traditional Chinese medicine, the sea buckthorn (Hippophae rhamnoides L.)
      has a long history in the treatment of ischemic heart disease and circulatory
      disorders. However, the active compounds responsible for and the underlying
      mechanisms of these effects are not fully understood. In this article,
      isorhamnetin pretreatment counteracted H(2)O(2)-induced apoptotic damage in H9c2
      cardiomyocytes. Isorhamnetin did not inhibit the death receptor-dependent or
      extrinsic apoptotic pathways, as characterized by its absence in both caspase-8
      inactivation and tBid downregulation along with unchanged Fas and TNFR1 mRNA
      levels. Instead, isorhamnetin specifically suppressed the mitochondria-dependent
      or intrinsic apoptotic pathways, as characterized by inactivation of caspase-9
      and -3, maintenance of the mitochondrial membrane potential (DeltaPsim), and
      regulation of a series of Bcl-2 family genes upstream of DeltaPsim. The anti
      apoptotic effects of isorhamnetin were linked to decreased ROS generation.
      H(2)O(2) activated ERK and p53, whereas isorhamnetin inhibited their activation.
      ERK overexpression overrode the isorhamnetin-induced inhibition of the intrinsic
      apoptotic pathway in H9c2 cardiomyocytes, which indicated that an ERK-dependent
      pathway was involved. Furthermore, N-acetyl cysteine (a potent ROS scavenger)
      could attenuate the H(2)O(2)-induced apoptosis. However, PD98059 (an ERK-specific
      inhibitor) could not effectively antagonize ROS generation, which indicates that
      ROS may be an upstream inducer of ERK. In conclusion, isorhamnetin inhibits the
      H(2)O(2)-induced activation of the intrinsic apoptotic pathway via ROS scavenging
      and ERK inactivation. Therefore, isorhamnetin is a promising reagent for the
      treatment of ROS-induced cardiomyopathy.

PMID- 21948484
TI  - Optimum threshold estimation based on cost function in a multistate diagnostic
      setting.
AB  - In the diagnostic area, the usual setting considers two populations: nondiseased
      and diseased. The use of the standard ROC analysis methodology is well
      established. Sometimes, however, diagnostic problems inherently include more than
      two classification states. For example, 'yes, uncertain, no' or 'low, normal,
      high'. Here we consider a three-normal distribution setting and derive estimators
      for the optimum thresholds between states based on a cost function. These
      estimators can be extended for clinical contexts with more than three states.
      This approach is well known for the two-state setting and its advantage lies in
      the fact that it accounts for the specific context's properties, such as disease
      prevalence and classification costs. Here we calculated the variance of the
      estimators by the use of parametric methods on nonlinear equations and we
      constructed confidence intervals accounting for possible uncertainty in the
      threshold estimation. We conducted a simulation study to assess the performance
      of these estimators and the confidence intervals. Comparisons with the naive
      threshold estimation method of joining the distributions two-by-two and applying
      standard ROC techniques proved that the latter method is not reliable for all
      parameter combinations and should be avoided.

PMID- 21948483
TI  - Dietary vitamin A intake and incidence of gastric cancer in a general Japanese
      population: the Hisayama Study.
AB  - BACKGROUND: The results of prospective studies examining the association between
      dietary vitamin A intake and the risk of gastric cancer have often been
      conflicting. The objective of this study was to investigate this issue in a
      general Japanese population. METHODS: A total of 2,467 community-dwelling
      Japanese subjects aged 40 years or older were followed up prospectively for 14
      years. Dietary vitamin A intake was estimated using a semiquantitative food
      frequency method. RESULTS: During the follow-up period, gastric cancer developed
      in 93 subjects. The age- and sex-adjusted incidence of gastric cancer rose
      progressively with increasing levels of dietary vitamin A intake: at 2.2, 3.0,
      3.8, and 4.5 per 1,000 person-years for quartile groups defined by dietary
      vitamin A intake levels of <639, 639-837, 838-1,061, and >1,061 MUg retinol
      equivalents (RE)/day, respectively (P for trend <0.01). The risk of gastric
      cancer was significantly higher in the fourth quartile than in the first one even
      after multivariate adjustment [hazard ratio (HR) = 1.47, 95% confidence interval
      (CI) = 0.70-3.09, P = 0.30 for the second quartile; HR = 1.85, 95% CI = 0.82
      4.18, P = 0.14 for the third quartile; HR = 2.96, 95% CI = 1.12-7.80, P = 0.03
      for the fourth quartile]. Comparable effects of vitamin A intake were observed
      irrespective of the location or histological type of gastric cancer. The HR for
      gastric cancer increased significantly only in subjects with a combination of
      high vitamin A intake (>1,061 MUg RE/day) and Helicobacter pylori infection.
      CONCLUSIONS: Our findings suggest that dietary vitamin A intake is clearly
      associated with the risk of gastric cancer in the general Japanese population.

PMID- 21948485
TI  - Microbial utilization of crude glycerol for the production of value-added
      products.
AB  - Energy fuels for transportation and electricity generation are mainly derived
      from finite and declining reserves of fossil hydrocarbons. Fossil hydrocarbons
      are also used to produce a wide range of organic carbon-based chemical products.
      The current global dependency on fossil hydrocarbons will not be environmentally
      or economically sustainable in the long term. Given the future pessimistic
      prospects regarding the complete dependency on fossil fuels, political and
      economic incentives to develop carbon neutral and sustainable alternatives to
      fossil fuels have been increasing throughout the world. For example, interest in
      biodiesel has undergone a revival in recent times. However, the disposal of crude
      glycerol contaminated with methanol, salts, and free fatty acids as a by-product
      of biodiesel production presents an environmental and economic challenge.
      Although pure glycerol can be utilized in the cosmetics, tobacco, pharmaceutical,
      and food industries (among others), the industrial purification of crude glycerol
      is not economically viable. However, crude glycerol could be used as an organic
      carbon substrate for the production of high-value chemicals such as 1,3
      propanediol, organic acids, or polyols. Microorganisms have been employed to
      produce such high-value chemicals and the objective of this article is to provide
      an overview of studies on the utilization of crude glycerol by microorganisms for
      the production of economically valuable products. Glycerol as a by-product of
      biodiesel production could be used a feedstock for the manufacture of many
      products that are currently produced by the petroleum-based chemical industry.

PMID- 21948487
TI  - The effect of porosity on drug release kinetics from vancomycin
      microsphere/calcium phosphate cement composites.
AB  - The influence of porosity on release profiles of antibiotics from calcium
      phosphate composites was investigated to optimize the duration of treatment. We
      hypothesized, that by the encapsulation of vancomycin-HCl into biodegradable
      microspheres prior admixing to calcium phosphate bone cement, the influence of
      porosity of the cement matrix on vancomycin release could be reduced.
      Encapsulation of vancomycin into a biodegradable poly(lactic co-glycolic acid)
      copolymer (PLGA) was performed by spray drying; drug-loaded microparticles were
      added to calcium phosphate cement (CPC) at different powder to liquid ratios
      (P/L), resulting in different porosities of the cement composites. The effect of
      differences in P/L ratio on drug release kinetics was compared for both the
      direct addition of vancomycin-HCl to the cement liquid and for cement composites
      modified with vancomycin-HCl-loaded microspheres. Scanning electron microscopy
      (SEM) was used to visualize surface and cross section morphology of the different
      composites. Brunauer, Emmett, and Teller-plots (BET) was used to determine the
      specific surface area and pore size distribution of these matrices. It could be
      clearly shown, that variations in P/L ratio influenced both the porosity of
      cement and vancomycin release profiles. Antibiotic activity during release study
      was successfully measured using an agar diffusion assay. However, vancomycin-HCl
      encapsulation into PLGA polymer microspheres decreased porosity influence of
      cement on drug release while maintaining antibiotic activity of the embedded
      substance.

PMID- 21948488
TI  - Facile and efficient control of bioadhesion on poly(dimethylsiloxane) by using a
      biomimetic approach.

PMID- 21948489
TI  - The UKNEQAS scheme for cerebrospinal fluid haem pigments: a paradigm for service
      improvement.
AB  - We describe the programme of an established External Quality Assurance (EQA)
      provider and a Specialist Advisory Group (SAG) to develop a successful EQA scheme
      for cerebrospinal fluid (CSF) haem pigments as an example of a professionally
      led, unfunded initiative with the real potential to benefit patients. Within
      three years, we had assured sample stability, stoichiometry, and published best
      practice guidelines, enabling both analytical results and interpretation to be
      assessed and reported with an educative summary of the desired responses.
      Misclassification scoring of analysis and interpretation was introduced.
      Following audit, guidelines were modified and republished. The outcomes were as
      follows: Participant numbers increased from 63 at inception to 150 10 years
      later; The percentage of participants using visual inspection, a poor practice
      indicator, decreased from 27% to less than 1%; In all, 94-100% of participants
      consistently detected minor increases in bilirubin over the last four years of
      the scheme; More than 93% of participants were able to interpret analytical
      results linked to straightforward clinical scenarios; Misclassification scoring
      demonstrated that more complex scenarios repeatedly posed problems and is the
      next challenge to address. Scheme success is attributed to the experience of the
      operator and the formation of a voluntary expert advisory group, with both
      concerned to advance science and patient safety and thus contribute unpaid time
      and effort in order to succeed. In times of fiscal constraint, such resource may
      not be so readily available, yet is a vital part of continuous quality
      improvement for the benefit of patients.

PMID- 21948486
TI  - Recurrent deletions and reciprocal duplications of 10q11.21q11.23 including CHAT
      and SLC18A3 are likely mediated by complex low-copy repeats.
AB  - We report 24 unrelated individuals with deletions and 17 additional cases with
      duplications at 10q11.21q21.1 identified by chromosomal microarray analysis. The
      rearrangements range in size from 0.3 to 12 Mb. Nineteen of the deletions and
      eight duplications are flanked by large, directly oriented segmental duplications
      of >98% sequence identity, suggesting that nonallelic homologous recombination
      (NAHR) caused these genomic rearrangements. Nine individuals with deletions and
      five with duplications have additional copy number changes. Detailed clinical
      evaluation of 20 patients with deletions revealed variable clinical features,
      with developmental delay (DD) and/or intellectual disability (ID) as the only
      features common to a majority of individuals. We suggest that some of the other
      features present in more than one patient with deletion, including hypotonia,
      sleep apnea, chronic constipation, gastroesophageal and vesicoureteral refluxes,
      epilepsy, ataxia, dysphagia, nystagmus, and ptosis may result from deletion of
      the CHAT gene, encoding choline acetyltransferase, and the SLC18A3 gene, mapping
      in the first intron of CHAT and encoding vesicular acetylcholine transporter. The
      phenotypic diversity and presence of the deletion in apparently normal carrier
      parents suggest that subjects carrying 10q11.21q11.23 deletions may exhibit
      variable phenotypic expressivity and incomplete penetrance influenced by
      additional genetic and nongenetic modifiers.

PMID- 21948490
TI  - Variation in phlebotomy techniques in emergency medicine and the incidence of
      haemolysed samples.
AB  - BACKGROUND: Phlebotomy is a potential cause of preanalytical errors. We have
      observed phlebotomy in routine practice in a busy Emergency Department, to see
      how current practice compares with optimal blood sampling. METHODS: Phlebotomy
      episodes were audited and compared with standard procedures. A computer-based
      search of the number of haemolysed samples from Emergency Medicine and hospital
      inpatients was reviewed. RESULTS: Four different ways of taking blood were
      observed: cannulation and a syringe (38%), cannula with evacuated tube and
      adaptor (42%), syringe and needle into vein (14%) and evacuated tube system used
      conventionally (6%). Where a syringe was used, two methods of transfer into the
      sample tube were observed; needle kept on with cap piercing (77%) and needle and
      evacuated cap both removed (23%). On 20 out of 50 phlebotomy episodes (40%), the
      potassium-EDTA tube was filled prior to the biochemistry serum gel tube. A search
      of the laboratory computer records for ward-based phlebotomy found 30 of 1034
      samples were haemolysed (2.9%). In the 50 phlebotomy episodes in the Majors area
      of the Emergency Department, 24% produced a haemolysed sample (P < 0.0001). For
      samples taken from all areas of Emergency Medicine over a seven-day period, 52 of
      485 were haemolysed (10.7%; P < 0.0001). CONCLUSIONS: This study has shown that
      phlebotomy techniques in the Emergency Department deviate from standard practice
      significantly. This may well be a reason for the much higher frequency of
      haemolysed samples and with the wrong order of collection the possibility of
      potassium-EDTA-contaminated samples.

PMID- 21948491
TI  - A patient with a metastatic gastroenteropancreatic endocrine carcinoma causing
      hyperinsulinaemic hypoglycaemia and the carcinoid syndrome.
AB  - We present the case of a 57-year-old patient who initially presented with a
      constellation of symptoms including intense pruritis, flushing and diarrhoea.
      Following several months clinical deterioration, the patient was investigated
      radiologically, where multiple hepatic tumours were identified. Liver biopsy
      confirmed the presence of a well-differentiated metastatic gastroenteropancreatic
      endocrine carcinoma with biochemical evidence of serotonin secretion. Over a
      period of six months, the clinical course of the patient's disease progressed
      whereby severe hypoglycaemia became the major manifestation. Subsequent
      biochemical investigations confirmed the diagnosis of an insulinoma. Extensive
      radiological investigation revealed a solitary primary pancreatic tumour,
      indicating the presence of a metastatic pancreatic endocrine tumour (PET)
      secreting both insulin and serotonin. The patient was treated with a chemotherapy
      regimen consisting of 12 cycles of 5-fluorouracil/oxaliplatin, responding
      clinically - improved World Health Organization performance score from 3 to 1,
      biochemically - significantly reduced plasma chromogranin A and cancer antigen 19
      9 concentrations and improved liver function tests, and radiologically - reduced
      pancreatic and hepatic tumour size. This is the first report of a primary PET
      secreting insulin and serotonin. Due to the association of serotonin-secreting
      gastroenteropancreatic endocrine tumours (GEP-ETs) with multiple endocrine
      neoplasia type-1 (MEN1) and biochemical evidence of an insulinoma, MEN1 should
      also be considered in such cases. The case provides further evidence for the
      biological heterogeneity of GEP-ETs and the myriad secretory humoral products and
      resultant clinical syndromes arising from such tumours.

PMID- 21948492
TI  - Long-term safety and efficacy of the recombinant human growth hormone
      Omnitrope(r) in the treatment of Spanish growth hormone deficient children:
      results of a phase III study.
AB  - INTRODUCTION: This phase III study in growth hormone (GH) deficient (GHD)
      children with growth retardation was designed to demonstrate the safety and
      efficacy of longterm treatment with the recombinant human GH Omnitrope(r) (Sandoz
      BioPharmaceuticals, Holzkirchen, Germany). METHODS: Treatment-naive, prepubertal
      Spanish children (n=70) with isolated GHD were treated with Omnitrope 0.03
      mg/kg/day subcutaneously. Changes in height, height standard deviation score
      (HSDS), height velocity (HV), HV standard deviation score (HVSDS), serum insulin
      like growth factor (IGF)-1, and insulin-like growth factor binding protein
      (IGFBP)-3 levels were recorded. RESULTS: Omnitrope treatment provided a good
      growth response after 4 years, shown by a significant increase in mean body
      height (31.1 cm [95% CI: 29.6-32.6]), HSDS (Tanner) (1.42 [1.13-1.70]), HV (2.4
      cm [1.7-3.1]), and HVSDS values (3.5 [2.7-4.3]). Mean IGF-1 and IGFBP-3 serum
      levels also increased significantly. CONCLUSION: At a dose of 0.03 mg/kg/day,
      Omnitrope was safe, effective, and well tolerated during long-term treatment of
      children with GHD.

PMID- 21948493
TI  - On the role of excitonic interactions in carotenoid-phthalocyanine dyads and
      implications for photosynthetic regulation.
AB  - In two recent studies, energy transfer was reported in certain phthalocyanine
      carotenoid dyads between the optically forbidden first excited state of
      carotenoids (Car S(1)) and phthalocyanines (Pcs) in the direction Pc -> Car S(1)
      (Kloz et al., J Am Chem Soc 133:7007-7015, 2011) as well as in the direction Car
      S(1) -> Pc (Liao et al., J Phys Chem A 115:4082-4091, 2011). In this article, we
      show that the extent of this energy transfer in both directions is closely
      correlated in these dyads. This correlation and the additional observation that
      Car S(1) is instantaneously populated after Pc excitation provides evidence that
      in these compounds excitonic interactions can occur. Besides pure energy transfer
      and electron transfer, this is the third type of tetrapyrrole-carotenoid
      interaction that has been shown to occur in these model compounds and that has
      previously been proposed as a photosynthetic regulation mechanism. We discuss the
      implications of these models for photosynthetic regulation. The findings are also
      discussed in the context of a model in which both electronic states are
      disordered and in which the strength of the electronic coupling determines
      whether energy transfer, excitonic coupling, or electron transfer occurs.

PMID- 21948494
TI  - The foundations for today's future.

PMID- 21948496
TI  - Observation of increased venous gas emboli after wet dives compared to dry dives.
AB  - INTRODUCTION: Testing of decompression procedures has been performed both in the
      dry and during immersion, assuming that the results can be directly compared. To
      test this, the aim of the present paper was to compare the number of venous gas
      bubbles observed following a short, deep and a shallow, long air dive performed
      dry in a hyperbaric chamber and following actual dives in open water. METHODS:
      Fourteen experienced male divers participated in the study; seven performed dry
      and wet dives to 24 metres' sea water (msw) for 70 minutes; seven divers
      performed dry and wet dives to 54 msw for 20 minutes. Decompression followed a
      Buhlmann decompression procedure. Immediately following the dive, pulmonary
      artery bubble formation was monitored for two hours. The results were graded
      according to the method of Eftedal and Brubakk. RESULTS: All divers completed the
      dive protocol, none of them showed any signs of decompression sickness. During
      the observation period, following the shallow dives, the bubbles increased from
      0.1 bubbles per cm 2 after the dry dive to 1.4 bubbles per cm 2 after the wet
      dive. Following the deep dives, the bubbles increased from 0.1 bubbles per cm 2
      in the dry dive to 2.4 bubbles per cm 2 in the wet dive. Both results are highly
      significant (P = 0.0001 or less). CONCLUSIONS: The study has shown that diving in
      water produces significantly more gas bubble formation than dry diving. The
      number of venous gas bubbles observed after decompression in water according to a
      rather conservative procedure, indicates that accepted standard decompression
      procedures nevertheless induce considerable decompression stress. We suggest that
      decompression procedures should aim at keeping venous bubble formation as low as
      possible.

PMID- 21948497
TI  - Risk factors and clinical outcome in military divers with neurological
      decompression sickness: influence of time to recompression.
AB  - BACKGROUND: This study was designed to examine the influence of short delay to
      recompression and other risk factors associated with the development of severe
      neurological decompression sickness (DCS) in military divers. METHODS: Fifty-nine
      divers with DCS treated in less than 6 hours from onset of symptoms to hyperbaric
      recompression were included retrospectively. Diving parameters, symptom latency
      and recompression delay were analysed. Clinical symptoms were evaluated for both
      the acute event and one month later. RESULTS: Median delay to hyperbaric
      treatment was 35 min (2-350 min). Resolution was incomplete after one month in
      25.4 % of divers with DCS. Multivariate analysis demonstrated that severe
      symptoms, classified as sensory and motor deficits or the presence of bladder
      dysfunction, were predictors of poor recovery with adjusted odds ratios (OR) of
      4.1 (1.12 to 14.92) and 9.99 (1.5 to 66.34) respectively. There was a
      relationship between a longer delay to treatment and incomplete recovery, but the
      increased risk appeared negligible with an adjusted OR of 1.01 (1-1.02).
      CONCLUSION: Our results suggest that neurological severity upon occurrence is the
      main independent risk factor associated with a poor outcome in military divers
      with DCS. Clinical recovery was not dramatically improved in this series when
      recompression treatment was performed promptly.

PMID- 21948498
TI  - Retinal artery occlusion: visual outcome after treatment with hyperbaric oxygen.
AB  - METHODS: We describe a case series of 11 patients with retinal artery occlusion
      treated with hyperbaric oxygen therapy (HBOT) at Intermountain Dixie Regional
      Medical Center between 2005 and 2009. We then combined data from our case series
      with data from two other case series to report on a combined total of 51
      patients. RESULTS: Eight of our 11 patients achieved improved visual acuity.
      Analysis of the combined case series showed that 74 % of patients treated with
      HBOT had improvement in visual acuity (P < 0.0001) with 53 % improving two lines
      or more on a modified Snellen value. The combined case series also showed that
      visual acuity improved in all time-from-occlusion to treatment categories,
      ranging from less than 8 hours to six days. CONCLUSIONS: We recommend
      consideration of HBOT for patients who present with recent retinal artery
      occlusion. Hyperbaric centres treating these patients should consider forming a
      central registry of standardised data to prospectively study the results of
      therapy.

PMID- 21948499
TI  - The need for optimisation of post-dive ultrasound monitoring to properly evaluate
      the evolution of venous gas emboli.
AB  - Audio Doppler ultrasound and echocardiographic techniques are useful tools for
      investigating the formation of inert gas bubbles after hyperbaric exposure and
      can help to assess the risk of occurrence of decompression sickness. However,
      techniques, measurement period and regularity of measurements must be
      standardised for results to be comparable across research groups and to be of any
      benefit. There now appears to be a trend for fewer measurements to be made than
      recommended, which means that the onset, peak and cessation of bubbling may be
      overlooked and misreported. This review summarises comprehensive Doppler data
      collected over 15 years across many dive profiles and then assesses the
      effectiveness of measurements made between 30 and 60 minutes (min) post-dive
      (commonly measured time points made in recent studies) in characterising the
      evolution and peak of venous gas emboli (VGE). VGE evolution in this dive series
      varied enormously both intra- and inter-individually and across dive profiles.
      Median, rather than mean values are best reported when describing data which have
      a non-linear relation to the underlying number of bubbles, as are median peak
      grades, rather than maximum, which may reflect only one individual's data. With
      regard to monitoring, it is apparent that the evolution of VGE cannot be
      described across multiple dive profiles using measurements made at only 30 to 60
      min, or even 90 min post-dive. Earlier and more prolonged measurement is
      recommended, while the frequency of measurements should also be increased; in
      doing so, the accuracy and value of studies dependent on bubble evolution will be
      improved.

PMID- 21948500
TI  - Maintenance of negative-pressure wound therapy while undergoing hyperbaric oxygen
      therapy.
AB  - BACKGROUND: Both negative wound pressure therapy (NPWT) and hyperbaric oxygen
      therapy (HBOT) are useful modalities in the treatment of problem wounds. However,
      none of the commercially available portable negative-pressure devices have been
      certified safe for use in a recompression chamber. Thus, the NPWT device is
      removed while the patient undergoes HBOT. The purpose of this study is to
      demonstrate that wound negative pressure can be effectively and safely maintained
      during HBOT. PATIENTS AND METHODS: In a small, prospective, randomised crossover
      trial, we used commonly available clinical materials to connect the NPWT suction
      tubing to the negative suction generating device in the hyperbaric chamber. Six
      patients each underwent one HBOT session with continuous NPWT and one HBOT
      session without concurrent NPWT. We assessed the patient's pain score, the amount
      of exudate aspirated by the NPWT during HBOT, and the appearance of the wound
      dressing after each session was assessed in a blinded manner. RESULTS: There were
      no differences in pain scores between the two HBOT sessions. The amount of
      exudate aspirated during HBOT with NPWT ranged from 5 to 12 ml. Five of the six
      patients had a better appearance scoring of their dressing when NPWT was
      maintained during HBOT (P = 0.006). CONCLUSION: We successfully demonstrated a
      simple design that allows the maintenance of NPWT during HBOT without causing
      additional pain, and with continued extraction of exudate. The maintenance of
      NPWT during HBOT also allowed the dressing to be maintained undisturbed.

PMID- 21948501
TI  - The influence of a hyperbaric environment and increased oxygen partial pressure
      on the corrosion of dental alloys.
AB  - OBJECTIVES: The purpose of this in-vitro study was to determine whether there is
      a correlation between a hyperbaric environment or increased oxygen partial
      pressure and the corrosion of dental alloys used for dental restorations in
      divers. METHOD AND MATERIALS: Samples of three commercially available dental
      alloys (palladium-based, reduced-gold-content and high-gold-content) were tested
      in the DIN EN ISO 1562 static immersion test and the amount of dissolved ions
      measured by atomic absorption spectrometry. The specimens were exposed to one of
      the following three conditions: normobaric and normoxic conditions (PO2 21 kPa);
      608 kPa (6 bar, PO2 127 kPa) pressurised air in a pressure chamber or 506 kPa (5
      bar, PO2 304 kPa) pressurised nitrox in a pressure chamber. RESULTS: None of the
      exposures suggested a correlation between increased ion solubility as a measure
      of corrosion and increased ambient pressure of the three alloys. The reduced-gold
      content alloy released zinc ions at twice the weekly recommended dose. When the
      palladium-based alloy was exposed to a hyperbaric or hyperbaric/hyperoxic
      environment, ion solubility increased only slightly for gallium and silver.
      CONCLUSIONS: Within the limited sample size of the current study it can be
      concluded that hyperbaric and/or hyperoxic conditions do not seem to be a risk
      for increased corrosion for any of the three tested alloys.

PMID- 21948502
TI  - Malignant otitis externa: experience with hyperbaric oxygen therapy.

PMID- 21948504
TI  - Chromatin structure and expression of the AMPA receptor subunit Glur2 in human
      glioma cells: major regulatory role of REST and Sp1.
AB  - It has been suggested that reduced glutamate receptor expression protects glioma
      cells from glutamate toxicity. GluR2 is the critical subunit of the GluR2 subtype
      of AMPA glutamate receptors as this subunit determines the Ca(2+) permeability of
      the receptor. The gene encoding the GluR2 subtype of AMPA receptors has been
      described as a target gene for the transcription repressor REST. However, we
      recently showed that the GluR2 gene is not regulated by REST in several neuronal
      and neuroendocrine cell lines, due to a repressive chromatin environment. Here,
      we show that the GluR2 gene has an open chromatin configuration in human glioma
      cells. Overexpression of REST reduced GluR2 mRNA levels while shRNA-mediated
      depletion of REST or expression of a REST mutant, that contained a
      transcriptional activation domain, enhanced GluR2 expression. Incubation with
      trichostatin A (TSA), a histone deacetylase inhibitor, induced acetylation of
      histone 4 of the GluR2 locus in glioma cells, leading to an upregulation of GluR2
      expression. Together, these data suggest that REST is responsible for the reduced
      expression of GluR2 in glioma cells. The transcription factor Sp1 additionally
      binds under physiological conditions to the GluR2 gene in human glioma cells and
      expression of a dominant-negative mutant of Sp1 reduced expression of GluR2.
      Thus, the regulation via Sp1 represents a further control point for GluR2
      expression in glioma cells. Together, we show that the GluR2 gene is embedded
      into an open chromatin configuration in glioma cells and expression of GluR2 is
      controlled by REST and Sp1.

PMID- 21948505
TI  - An easy and effective demonstration of enzyme stereospecificity and equilibrium
      thermodynamics.
AB  - Enzyme stereospecificity and equilibrium thermodynamics can be demonstrated using
      the coupling of two amino acid derivatives by Thermoase C160. This protease will
      catalyze peptide bond formation between Z-L-AspOH and L-PheOMe to form the
      Aspartame precursor Z-L-Asp-L-PheOMe. Reaction completion manifests itself by
      precipitation of the product. As the product has almost zero solubility, the
      equilibrium favors condensation and thus a normally hydrolytic enzyme catalyzes
      the opposite reaction. Neither Z-D-AspOH with L-PheOMe nor Z-L-AspOH with D
      PheOMe produces any visible product.

PMID- 21948506
TI  - An interactive modeling lesson increases students' understanding of ploidy during
      meiosis.
AB  - Chromosome structure is confusing to students at all levels, and chromosome
      behavior during meiosis is a notoriously difficult topic. Undergraduate biology
      majors are exposed to the process of meiosis numerous times during their
      presecondary and postsecondary education, yet understanding of key concepts, such
      as the point at which haploidy is established, does not improve substantially
      with repeated exposure. Based on student's drawings, 96% of intermediate-level
      biology majors have unclear or incorrect ideas about meiosis. Students have
      difficulty diagramming the process of meiosis starting with three unreplicated
      pairs of chromosomes, and even when they can produce an accurate diagram, they
      are unclear how to assign the terms "haploid" and "diploid." We designed an
      interactive lesson based on constructivist theory to address these issues in a
      large lecture class. Pretest and posttest scores showed a significant improvement
      in students' understanding of ploidy compared to a parallel class taught in the
      traditional way (e.g. using the textbook diagrams). In interviews afterward,
      those students whose scores improved on exams specifically pointed to the
      features of the in-class modeling that were deliberately incorporated for that
      purpose.

PMID- 21948507
TI  - A participatory learning approach to biochemistry using student authored and
      evaluated multiple-choice questions.
AB  - A participatory learning approach, combined with both a traditional and a
      competitive assessment, was used to motivate students and promote a deep approach
      to learning biochemistry. Students were challenged to research, author, and
      explain their own multiple-choice questions (MCQs). They were also required to
      answer, evaluate, and discuss MCQs written by their peers. The technology used to
      support this activity was PeerWise--a freely available, innovative web-based
      system that supports students in the creation of an annotated question
      repository. In this case study, we describe students' contributions to, and
      perceptions of, the PeerWise system for a cohort of 107 second-year biomedical
      science students from three degree streams studying a core biochemistry subject.
      Our study suggests that the students are eager participants and produce a large
      repository of relevant, good quality MCQs. In addition, they rate the PeerWise
      system highly and use higher order thinking skills while taking an active role in
      their learning. We also discuss potential issues and future work using PeerWise
      for biomedical students.

PMID- 21948508
TI  - Thermal regulation of membrane lipid fluidity by a two-component system in
      Bacillus subtilis.
AB  - This article describes a simple and robust laboratory exercise on the regulation
      of membrane unsaturated fatty acid composition in bacteria by a decrease in
      growth temperature. We take advantage of the well characterized Des pathway of
      Bacillus subtilis, composed of a Delta5-desaturase (encoded by the des gene) and
      the canonical two-component system DesK-DesR, to study the transcriptional
      regulation of des during cold shock. Students analyze the expression of a
      reporter transcriptional fusion between the des promoter and the bacterial lacZ
      gene in a wild-type B. subtilis strain and in des or desK-desR mutants grown
      under different culture conditions. Measurements of beta-galactosidase activity
      allow them to investigate how the Des pathway works and to assess the role of
      each component of this regulatory system.

PMID- 21948509
TI  - Mapping maize genes: a series of research-based laboratory exercises.
AB  - Open-ended, inquiry-based multiweek laboratory exercises are the key elements to
      increasing students' understanding and retention of the major biological
      concepts. Including original research into undergraduate teaching laboratories
      has also been shown to motivate students and improve their learning. Here, we
      present a series of original laboratory exercises on fine mapping novel maize
      mutations producing interesting phenotypes. In this 4-week lab series, students
      get involved in the whole process of identifying novel genes controlling specific
      phenotypes, from phenotype characterization and choosing appropriate molecular
      markers to calculating the genetic distance between the mutation and the marker
      and finding possible candidate genes using a complete genome sequence. We chose
      to use maize mutant lines produced by TILLING project. These lines have been
      partially mapped to a chromosomal bin by a high-throughput bulk segregant
      analysis; however, the exact map positions for these mutations have never been
      determined. Mapping these novel maize mutations provides students with the
      opportunity to conduct original research as a part of their classroom experience
      and to contribute to the field of maize genetics. The laboratory series was well
      received by the students, and the assessment results demonstrated an improvement
      of student learning of gene mapping, molecular marker analysis, and positional
      cloning concepts.

PMID- 21948510
TI  - The "Frankenplasmid" lab: an investigative exercise for teaching recombinant DNA
      methods.
AB  - We describe an investigative laboratory module designed to give college
      undergraduates strong practical and theoretical experience with recombinant DNA
      methods within 3 weeks. After deducing restriction enzyme maps for two different
      plasmids, students ligate the plasmids together in the same reaction, transform
      E. coli with this mixture of ligated DNA, and plate the cells on media that
      specifically select for hybrid plasmids. The main goal of the assignment is for
      students to deduce the gene map of one hybrid "Frankenplasmid" using the LacZ
      phenotype of its transformants, PCR, and restriction mapping. Our protocol
      results in a number of possible outcomes, meaning that students are mapping truly
      unknown plasmids. The open-ended nature of this assignment results in an
      effective module that teaches recombinant DNA procedures while engaging students
      with its investigative approach, increasing complexity, and puzzle-like quality.
      Moreover, the modular design of the activity allows it to be adapted to a more
      limited schedule, introductory courses, or more advanced courses.

PMID- 21948511
TI  - What bacteria are living in my food? An open-ended practical series involving
      identification of unknown foodborne bacteria using molecular techniques.
AB  - This open-ended practical series titled "Molecular Identification of Unknown Food
      Bacteria" which extended over a 6-week period was designed with the aims of
      giving students an opportunity to gain an understanding of naturally occurring
      food bacteria and skills in contemporary molecular methods using real food
      samples. The students first isolated two unknown bacterial strains from two food
      sources from which they extracted DNA and performed PCR targeting the 16S rRNA
      gene. Gel electrophoresis was used to analyze both genomic DNA preparations and
      PCR products. Following purification of PCR products, DNA sequencing was carried
      out and sequence trace quality was analyzed. The students successfully identified
      the two unknown bacteria using the BLAST search engine and a wide variety of
      different organisms were found. Assessment of their understanding of the
      procedure and ability to explain their findings using supporting primary research
      literature was via an individually prepared written report. Feedback from
      students over 2 years (n = 52) in a questionnaire revealed that the practical
      series was an engaging learning experience and lead to perceived improvements in
      knowledge of molecular techniques and bioinformatics and also about commonly
      occurring bacteria in foods.

PMID- 21948512
TI  - Cooperative learning for faculty: building communities of practice.

PMID- 21948513
TI  - Problem-solving test: restriction endonuclease mapping.

PMID- 21948514
TI  - Commentary: the meteoric rise of mobile technologies.

PMID- 21948515
TI  - Proteopedia entry: phosphoinositide 3-kinase.

PMID- 21948518
TI  - Plasma-assisted dissociation of organometallic vapors for continuous, gas-phase
      preparation of multimetallic nanoparticles.

PMID- 21948517
TI  - Enhancer-adoption as a mechanism of human developmental disease.
AB  - Disruption of the long-range cis-regulation of developmental gene expression is
      increasingly recognized as a cause of human disease. Here, we report a novel type
      of long-range cis-regulatory mutation, in which ectopic expression of a gene is
      driven by an enhancer that is not its own. We have termed this gain of regulatory
      information as "enhancer adoption." We mapped the breakpoints of a de novo 7q
      inversion in a child with features of a holoprosencephaly spectrum (HPES)
      disorder and severe upper limb syndactyly with lower limb synpolydactyly. The
      HPES plausibly results from the 7q36.3 breakpoint dislocating the sonic hedgehog
      (SHH) gene from enhancers that are known to drive expression in the early
      forebrain. However, the limb phenotype cannot be explained by loss of known SHH
      enhancers. The SHH transcription unit is relocated to 7q22.1, ~190 kb 3' of a
      highly conserved noncoding element (HCNE2) within an intron of EMID2. We show
      that HCNE2 functions as a limb bud enhancer in mouse embryos and drives ectopic
      expression of Shh in vivo recapitulating the limb phenotype in the child. This
      developmental genetic mechanism may explain a proportion of the novel or
      unexplained phenotypes associated with balanced chromosome rearrangements.

PMID- 21948519
TI  - Crystallization processes at the surface of polylactic acid-bioactive glass
      composites during immersion in simulated body fluid.
AB  - We report on the crystallization processes occurring at the surface of PDLLA
      Bioglass(r) composites immersed in simulated body fluid. Composites manufactured
      by injection molding and containing different amounts (0, 20, 30, and 50 wt %) of
      45S5 Bioglass(r) particles were tested for durations up to 56 days and compared
      with Bioglass(r) particles alone. Crystallization processes were followed by
      visual inspection, X-ray diffraction (with Rietveld analysis) and scanning
      electron microscopy. Both calcite and hydroxyapatite were formed at the surface
      of all materials, but their relative ratio was dependent on the Bioglass(r)
      content and immersion time. Hydroxyapatite was always the major phase after
      sufficient immersion time, insuring bioactivity of such composites especially for
      Bioglass(r) content higher than 30 wt %. A scenario of crystallization is
      proposed. Rapid degradation of the composites with 50 wt % was also observed
      during immersion. Therefore, composites with 30 wt % of Bioglass(r) particles
      seem to exhibit the best balance between bioactivity and stability at least
      during the first weeks of immersion in contact with body fluids.

PMID- 21948520
TI  - Long-lasting neuroprotective effect of sildenafil against 3,4
      methylenedioxymethamphetamine- induced 5-hydroxytryptamine deficits in the rat
      brain.
AB  - Sildenafil, given shortly before 3,4-methylenedioxymethamphetamine (MDMA),
      affords protection against 5-hydroxytryptamine (5-HT) depletions caused by this
      amphetamine derivative by an acute preconditioning-like mechanism. Because acute
      and delayed preconditionings do not share the same mechanisms, we investigated
      whether sildenafil would also protect the 5-HT system of the rat if given 24 hr
      before MDMA. For this, MDMA (3 * 5 mg/kg i.p., every 2 hr) was administered to
      rats previously treated with sildenafil (8 mg/kg p.o.). One week later, 5-HT
      content and 5-HT transporter density were measured in the striatum, frontal
      cortex, and hippocampus of the rats. Our findings indicate that sildenafil
      afforded significant protection against MDMA-induced 5-HT deficits without
      altering the acute hyperthermic response to MDMA or its metabolic disposition.
      Sildenafil promoted ERK1/2 activation an effect that was paralleled by an
      increase in MnSOD expression that persisted 24 hr later. In addition, superoxide
      and superoxide-derived oxidants, shown by ethidium fluorescence, increased after
      the last MDMA injection, an effect that was prevented by sildenafil pretreatment.
      Similarly, MDMA increased nitrotyrosine concentration in the hippocampus, an
      effect not shown by sildenafil-pretreated rats. In conclusion, our data
      demonstrate that sildenafil produces a significant, long-lasting neuroprotective
      effect against MDMA-induced 5-HT deficits. This effect is apparently mediated by
      an increased expression of MnSOD and a subsequent reduced susceptibility to the
      oxidative stress caused by MDMA.

PMID- 21948521
TI  - Musculoskeletal: what is different in children? Fall from bicycle; pain, and
      tenderness of right wrist.

PMID- 21948522
TI  - Genomic basis of endosymbiont-conferred protection against an insect parasitoid.
AB  - Bacterial endosymbionts exert a variety of beneficial effects on insect hosts. In
      pea aphids (Acyrthosiphon pisum), several inherited endosymbiont species protect
      their hosts against parasitoid wasps, which are major natural enemies. However,
      strains of these symbiont species vary in their ability to confer protection
      against parasitoids, with some conferring almost complete protection and others
      conferring almost none. In this study, two strains of the endosymbiont Regiella
      insecticola (R. insecticola 5.15 and R. insecticola LSR1) were found to differ in
      ability to protect pea aphids attacked by the parasitoid Aphidius ervi.
      Parasitism trials reveal that R. insecticola 5.15, but not R. insecticola LSR1,
      significantly reduced parasitoid success and increased aphid survivorship. To
      address the potential genetic basis of protection conferred by R. insecticola
      5.15 we sequenced the genome of this symbiont strain, and then compared its gene
      repertoire with that of the already sequenced nonprotective strain R. insecticola
      LSR1. We identified striking differences in gene sets related to eukaryote
      pathogenicity. The protective strain R. insecticola 5.15 encoded five categories
      of pathogenicity factors that were missing or inactivated in R. insecticola LSR1.
      These included genes encoding the O-antigen biosynthetic pathway, an intact Type
      1 Secretion System and its secreted RTX toxins, an intact SPI-1 Type 3 Secretion
      System and its effectors, hemin transport, and the two-component system PhoPQ.
      These five pathogenicity factors and translocation systems are hypothesized to
      collectively play key roles in the endosymbiont's virulence against parasitoids,
      resulting in aphid protection. Mechanisms through which these factors may target
      parasitoids are discussed.

PMID- 21948524
TI  - SPT6L encoding a putative WG/GW-repeat protein regulates apical-basal polarity of
      embryo in Arabidopsis.
AB  - In eukaryotes, a protein motif consisting of WG/GW repeats, also called the
      Argonaute (AGO) hook, is thought to be essential for binding AGO proteins to
      fulfill their functions in RNA-mediated gene silencing. Although a number of
      WG/GW-containing proteins have been computationally identified in Arabidopsis,
      their roles in plant growth and development are unknown. Here, we show that the
      Arabidopsis Suppressor of Ty insertion 6-like (SPT6L) gene, which encodes a
      protein with C-terminal WG/GW repeats, plays critical roles in embryonic
      development. SPT6L is evolutionarily conserved only in vascular plants, with
      varying numbers of C-terminal WG/GW repeats, which are plant-species specific.
      spt6l mutants formed embryos with an aberrant apical-basal axis, showing
      insufficient development of the basal domain and embryonic lethality. Expression
      domains of the class-III homeodomain-leucine zipper (HD-ZIP III) genes PHABULOSA
      (PHB) and PHAVOLUTA (PHV) were expanded in the spt6l embryo. In contrast, the
      PLETHORA1 (PLT1) gene, which acts antagonistically to the HD-ZIP III genes in
      specification of basal fate, was severely down-regulated in the spt6l mutant.
      Furthermore, the phb phv double mutations partially rescued aberrant basal
      development in the spt6l background and restored PLT1 expression. Collectively,
      our results indicate that SPT6L is essential for specification of the apical
      basal axis, partly by controlling the HD-ZIP III genes in embryos.

PMID- 21948523
TI  - Post-transcriptional exon shuffling events in humans can be evolutionarily
      conserved and abundant.
AB  - In silico analyses have established that transcripts from some genes can be
      processed into RNAs with rearranged exon order relative to genomic structure
      (post-transcriptional exon shuffling, or PTES). Although known to contribute to
      transcriptome diversity in some species, to date the structure, distribution,
      abundance, and functional significance of human PTES transcripts remains largely
      unknown. Here, using high-throughput transcriptome sequencing, we identify 205
      putative human PTES products from 176 genes. We validate 72 out of 112 products
      analyzed using RT-PCR, and identify additional PTES products structurally related
      to 61% of validated targets. Sequencing of these additional products reveals GT
      AG dinucleotides at >95% of the splice junctions, confirming that they are
      processed by the spliceosome. We show that most PTES transcripts are expressed in
      a wide variety of human tissues, that they can be polyadenylated, and that some
      are conserved in mouse. We also show that they can extend into 5' and 3' UTRs,
      consistent with formation via trans-splicing of independent pre-mRNA molecules.
      Finally, we use real-time PCR to compare the abundance of PTES exon junctions
      relative to canonical exon junctions within the transcripts from seven genes.
      PTES exon junctions are present at <0.01% to >90% of the levels of canonical
      junctions, with transcripts from MAN1A2, PHC3, TLE4, and CDK13 exhibiting the
      highest levels. This is the first systematic experimental analysis of PTES in
      human, and it suggests both that the phenomenon is much more widespread than
      previously thought and that some PTES transcripts could be functional.

PMID- 21948526
TI  - Cell death-inducing DFF45-like effector b (Cideb) is present in pancreatic beta
      cells and involved in palmitate induced beta-cell apoptosis.
AB  - BACKGROUND: Excessive accumulation of long-chain fatty acids in the pancreatic
      islets is associated with beta cell dysfunction and ultimately contributes to the
      pathogenesis of type 2 diabetes. It has been well proved that the cell death
      inducing DFF45-like effector b (Cideb) is involved in cell apoptosis and lipid
      metabolism. However, the expression and function of Cideb in endocrine pancreas
      remain to be investigated. METHODS: By using reverse transcript polymerase chain
      reaction, immunohistochemistry and Western blot, we observed the expression of
      Cideb in pancreas tissues and clonal beta-cell lines. The physiological role of
      Cideb was examined under the free fatty acid (FFA) administration and Cideb
      ribonucleic acid interference, and further analysis on apoptosis was measured by
      terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end
      labelling assay and caspase-3 activity. Nile red staining and quantitative
      evaluation of triglyceride were used to detect the lipid accumulation. The
      changes in esterification of FFA were traced by radiolabelled palmitate. RESULTS:
      Cideb was abundantly expressed in pancreas and mainly localized in beta cells.
      FFAs, especially palmitate, induced an obvious increase of Cideb expression in
      beta cell lines. Adenoviral-mediated overexpression of Cideb increased the
      apoptosis, whereas ribonucleic acid interference-based Cideb depletion in beta
      TC3 cells had no effect on apoptosis in normal condition. Palmitate
      supplementation led to beta cell lipoapoptosis, and Cideb silencing exacerbated
      the apoptosis induced by palmitate, reduced intracellular triglyceride content
      and aggravated FFA overload in beta cells. CONCLUSIONS: The present results
      suggest that increased Cideb expression upon palmitate exposure may be involved
      in beta cell lipoapoptosis through its influence on conversion of FFAs to lipid
      esters in lipid droplets.

PMID- 21948527
TI  - Decrease in the expression of N-methyl-D-aspartate receptors in the nucleus
      tractus solitarii induces antinociception and increases blood pressure.
AB  - N-methyl-D-aspartate receptors (NMDAR) have a role in cardiovascular control at
      the nucleus tractus solitarii (NTS), eliciting increases or decreases in blood
      pressure (BP), depending on the area injected with the agonists. In spite of the
      association between cardiovascular control and pain modulation, the effects of
      manipulating NMDAR in pain responses have never been evaluated. In this study, we
      decreased the expression of NMDAR in the NTS using gene transfer to target
      receptor subunits and evaluate long-term effects. Seven days after the injection
      of lentiviral vectors containing the NR1a subunit cDNA of NMDAR, in antisense
      orientation, into the intermediate NTS of Wistar rats, BP was measured, and the
      formalin test of nociception was performed. The antisense vector induced a
      decrease of NR1 expression in the NTS and elicited BP rises and hypoalgesia.
      Antisense vectors inhibited formalin-evoked c-Fos expression in the spinal cord,
      indicating decreased nociceptive activity of spinal neurons. Using a time-course
      approach, we verified that the onset of both the increases in BP and the
      hypoalgesia was at 4 days after vector injection into the NTS. The injection of
      NMDA into the NTS reversed the effects of antisense vectors in pain behavioral
      responses and spinal neuronal activation and decreased BP and heart rate. The
      present study shows that the NR1 subunit of the NMDAR at the NTS is critical in
      the regulation of tonic cardiovascular and nociceptive control and shows an
      involvement of the nucleus in the modulation of sustained pain.

PMID- 21948528
TI  - [Current status and future prospect of multimodality management of esophageal
      cancer].
AB  - The prevalence of esophageal cancer in China is significant. Surgery remains to
      be the mainstay treatment for esophageal cancer. Standardized surgical procedure
      and radical lymph node dissection is the base of multimodality treatment, which
      is also related to the success of the treatment and prognosis. At present,
      synchronized preoperative chemoradiation is recommended for operable esophageal
      cancer. Use of preoperative radiation is not associated with increased difficulty
      in performing surgery or increased complications. Preoperative chemotherapy alone
      is not recommended. NCCN recommends 5-fluorouracil-based adjuvant therapy
      administered synchronously with radiation. In China, postoperative synchronized
      chemoradiation is recommended for II(B-III) esophageal cancer. Large-scale, multi
      center, prospective controlled clinical trials are warranted to determine the
      optimal combination of therapeutic alternatives to benefit patients the most.

PMID- 21948529
TI  - Improving outcomes after esophagectomy: the importance of preventing
      postoperative pneumonia.
AB  - Outcomes after esophagectomy may be related to many factors, including the age of
      the patient, the stage of the tumor, the operative approach, and the incidence of
      postoperative morbidity. Pulmonary complications are the major source of
      morbidity and mortality following esophageal resection, and numerous studies have
      identified various factors associated with these complications. Preoperative
      factors affecting pulmonary complications include advanced age, poor nutritional
      status, and poor cardiopulmonary reserve, whereas preoperative chemoradiation
      therapy is not clearly associated with increased pulmonary complications.
      Intraoperative factors associated with increased rates of pulmonary complications
      include increased blood loss, prolonged operative times, advanced or proximal
      esophageal tumors, and more extensive operations, including the McKeown resection
      with three-field lymph node dissection. Postoperative factors associated with
      pulmonary complications include the development of atrial fibrillation, recurrent
      laryngeal nerve injury, and aspiration or other abnormality of deglutition.
      Potential maneuvers to limit the severity of pulmonary complications include
      smoking cessation prior to surgery, aggressive pulmonary toilet, and
      documentation of intact swallowing mechanisms prior to the resumption of oral
      intake after surgery.

PMID- 21948530
TI  - [Dispute and consensus about surgical approaches and lymph nodes excisional area
      of esophageal carcinoma].
AB  - Surgical approaches for esophageal carcinoma are many and varied. Minimally
      invasive techniques are increasingly used widely in esophagectomy as they not
      only ensure patients' therapeutic effects, but also reduce trauma and accelerate
      recovery. The lymph nodes excisional area of esophageal carcinoma is still in
      controversy. It is necessary to carry out further researches on selective lymph
      nodes excision, which can decrease complication rate and improve patients'
      survival in the meantime.

PMID- 21948531
TI  - [Protection on intestinal mucosa barrier during perioperative period of
      esophageal cancer].
AB  - Intestinal mucosa plays important roles in digestion, absorption and substance
      exchange between organism and external environment. Meanwhile, it is the largest
      immune organ and mucosal barrier, including mechanical, biological and immune
      barrier. A variety of diseases, especially postoperative complications, are
      associated with the damage of mucosal barrier. Esophageal cancer surgery is
      complex and many perioperative factors, especially hypoperfusion and fasting, may
      affect the integrity of intestinal barrier. Understanding of the mechanism of
      intestinal barrier (mechanical, biological and immune barrier), the physiological
      function of probiotics, and the benefit of early enteral nutrition to intestinal
      barrier are important components to achieve fast recovery after surgery for
      esophageal cancer.

PMID- 21948532
TI  - [Comparison of thoracoscopic esophagectomy in decubitus position with prone
      position].
AB  - OBJECTIVE: To compare the safety and efficacy between two different surgical
      approaches for thoracoscopic esophagectomy including left lateral decubitus
      position and prone position. METHODS: From January 2008 to December 2009, 88
      patients who underwent thoracoscopic esophagectomy were enrolled in this study.
      Among them, 52 patients were placed in decubitus position and 36 patients were
      placed in prone position. RESULTS: No conversion to thoracotomy occurred in
      either group. The operative time was shorter in the prone group than that in the
      decubitus group (70 +/- 20 min vs. 82 +/- 17 min, P<0.01). Blood loss during
      operation was less in the prone group(100 +/- 52 ml vs. 139 +/- 54 ml, P<0.01).
      More lymph nodes were harvested from chest in the prone group(12.2 +/- 6.2 vs.
      8.6 +/- 4.3, P<0.01). There was no significant difference between the two groups
      in morbidity. CONCLUSION: Thoracoscopic esophagectomy in prone position is
      associated with better exposure of surgical filed, shorter operative time, less
      blood loss, and more extensive lymph node dissection as compared to decubitus
      position.

PMID- 21948533
TI  - [Combination of single-port thoracoscopy and laparoscopy for the treatment of
      esophageal carcinoma: report of 6 cases].
AB  - OBJECTIVE: To study the feasibility and early results of radical resection of
      esophageal carcinoma using single-port thoracoscopy combined with laparoscopy.
      METHODS: From March 2010 to December 2010, 6 patients with esophageal carcinoma
      underwent radical resection by single-port thoracoscopy combined with laparoscopy
      in the General Hospital of People's Liberation Army. With the patients at a
      supine position, laparoscopy was performed to complete stomach mobilization and
      abdominal lymph node dissection. Thoracoscopy was then carried out with the
      patients lying on the left to mobilize the esophagus and dissect thoracic lymph
      nodes. Finally, the stomach was pulled into the thoracic cavity via the hiatus of
      the diaphragm to construct a tube-like stomach, which was then anastomosed to the
      esophagus using the OrVil system. RESULTS: No patient was converted to open
      surgery during the operation. The total operative time ranged from 200 to 320
      min. The mean laparoscopic time was 75(range, 45-90) min, and the mean
      thoracoscopic time 160(120-240) min. The mean intraoperative blood loss was
      220(160-300) ml. The mean lymph node retrieval was 12(9-18). No anastomotic
      fistula, chylothorax, lung infection were found postoperatively. CONCLUSION:
      After esophageal resection using single-port thoracoscopic and laparoscopy,
      reconstruction using OrVil system is safe and feasible.

PMID- 21948534
TI  - [Application of circular staplers in cervical esophagogastric anastomosis after
      esophageal cancer resection].
AB  - OBJECTIVE: To evaluate safety and feasibility of circular staplers in cervical
      esophagogastrostomy after esophageal cancer resection. METHODS: The clinical data
      of patients with esophageal carcinoma were analyzed retrospectively. These
      patients underwent esophagectomy and cervical esophagogastrostomy with mechanical
      staplers from August 2009 to April 2011 in the Henan Provincial People's
      Hospital. RESULTS: A total of 202 patients had the anastomosis performed
      successfully except for one case who had esophageal tear during anastomosis and
      required hand-sewn repair. There was no operative mortality. Six patients
      developed cervical anastomotic leakage after operation, and all were treated
      conservatively. There was no thoracic anastomotic leakage and other complications
      related to anastomosis. Two patients had obvious gastroesophageal reflux. After a
      median of 10.2 months of follow-up, there was no anastomotic stricture.
      CONCLUSION: Circular mechanical stapling in cervical esophagogastric anastomosis
      is a safe and feasible operative procedure.

PMID- 21948535
TI  - [Application of colonic interposition in the digestive tract reconstruction after
      esophagectomy].
AB  - OBJECTIVE: To evaluate the safety of colonic interposition after esophagectomy.
      METHODS: One hundred and thirty six patients with esophageal cancer underwent
      colonic interposition after esophagectomy in the Sichuan Tumor Hospital from
      October 1992 to October 2010. Clinical data of these patients were
      retrospectively reviewed. RESULTS: Out of the 136 patients, 118 grafts were
      transverse colon in clockwise peristalsis supplied by ascending branches of the
      left colonic artery. Twelve grafts were right part of transverse colon and
      ascending colon in clockwise peristalsis. Six grafts were left part of transverse
      colon and descending colon in counterclockwise peristalsis. All the 18 grafts
      were supplied by the middle colonic artery. The total perioperative complication
      rate was 26.4% (36/136), including anastomotic leakage in 15 cases, colon
      necrosis in 5 cases. The mortality was 12.5%(17/136), in which 5 patients died of
      colonic perforation, 4 died of colon necrosis, 4 died of severe lung infection
      after operation, 3 died of ARDS and 1 died of systemic infection of unknown
      origin. Anastomotic stenosis occurred in 2 patients, reflux in 2 cases, and 3
      patients suffered from bowel dysmotility. CONCLUSIONS: Colon interposition is a
      complex procedure with significant trauma, high morbidity, and mortality.
      However, it is a valid alternative to reconstruct the gastrointestinal tract when
      the stomach is not feasible.

PMID- 21948536
TI  - [Application of Ivor-Lewis esophagectomy in elderly patients with carcinoma in
      middle and lower esophagus].
AB  - OBJECTIVE: To evaluate the safety of Ivor-Lewis procedure for middle and lower
      esophageal carcinoma in the elderly. METHODS: From June 2009 to June 2010, 232
      cases aged over 60 years were diagnosed as esophageal carcinoma. These cases were
      randomly divided into two groups using table of random digits. One group
      underwent abdominal and right chest approaches for middle and lower esophageal
      carcinoma (Ivor-Lewis procedure, n=116). The other group underwent posterolateral
      left thoracal incisions(Sweet procedure, n=116). Intraoperative and postoperative
      parameters were compared. RESULTS: The radical resection rates in Ivor-Lewis and
      Sweet procedure were 95.7% and 92.2% respectively(P>0.05). The time required for
      opening the thorax was(47.2 +/- 5.2) min and (105.4 +/- 9.3) min(P=0.000),
      respectively. The respiratory failure rates were 1.7% and 6.9%(P=0.049). The
      incidences of supraventricular tachyarrhythmia were 3.4% and 10.3%, respectively.
      The overall complication rates were 22.4% and 34.5%(P=0.004). The perioperative
      mortalities were 1.7% and 3.4%(P>0.05). The postoperative ambulation time was
      (4.0 +/- 2.0)d and (4.8 +/- 3.7)d(P=0.046). The postoperative time in hospital
      was (11.5 +/- 4.7)d and (13.7 +/- 7.8)d(P=0.008). CONCLUSIONS: Ivor-Lewis
      procedure is associated with little damage to diaphragm, shorter intrathoracic
      operative time, minimal influence on cardiopulmonary function, less postoperative
      complications, and quicker recovery. This procedure should be considered as the
      first choice for middle and lower esophageal carcinoma in the elderly.

PMID- 21948537
TI  - [Multidisciplinary therapy for multi-focal esophageal cancer].
AB  - OBJECTIVE: To explore the management strategies and outcome of treatment for
      multi-focal esophageal carcinoma. METHODS: Twenty two patients with multi-focal
      esophageal carcinoma who underwent esophagectomy by a single surgeon team from
      March 2000 to March 2011 at the Beijing Cancer Hospital were reviewed
      retrospectively. The clinical and pathological characters were analyzed, and the
      outcome was compared with that of 471 patients with single esophageal carcinoma
      who received esophagectomy by the same surgeon team during the same period.
      RESULTS: Eighteen out of 22 patients with multi-focal esophageal cancer underwent
      esophagectomy via transthoracic approach while 4 patients via transhiatal. Eight
      patients received neoadjuvant chemotherapy and 15 patients received adjuvant
      chemotherapy. Four hundred and seventy-one out of 471 patients with single
      esophageal cancer underwent esophagectomy via transthoracic approach while 60
      patients via transhiatal. One hundred and fourty-eight patients received
      neoadjuvant chemotherapy and 267 patients received adjuvant chemotherapy. The 3
      year survival of the 22 patients with multi-focal esophageal carcinoma was 41.9%,
      and the median survival time was 29.2 months. The 3-year survival of the 471
      patients with single esophageal carcinoma was 54.7%, and the median survival time
      was 46.8 months. There was no significant difference in survival between the two
      groups(P=0.051). CONCLUSIONS: The prognosis of patients with multi-focal
      occurrence esophageal carcinoma was poor. Extended esophageal resection may be
      beneficial to these patients with concurrent systemic chemotherapy.

PMID- 21948538
TI  - [Peroral endoscopic myotomy for esophageal achalasia: report of 42 cases].
AB  - OBJECTIVE: To evaluate the efficacy and the feasibility of peroral endoscopic
      myotomy (POEM) for esophageal achalasia (AC). METHODS: The clinical data of 42
      patients diagnosed as AC and received POEM in the Zhongshan Hospital of Fudan
      University between August 2010 and March 2011 were reviewed retrospectively. The
      key procedures of POEM included esophageal mucosal incision, submucosal
      "tunneling" by endoscopic submucosal dissection(ESD) technique, endoscopic
      myotomy of the circular muscle, and closure of mucosal incision by hemostatic
      clips. RESULTS: The mean age of 42 cases was 43.9(range 10-70) years. The mean
      duration of disease was 8.7 years (range, 3 months to 50 years). The mean
      operative time was (68.5 +/- 25.5) (range 23-180) minutes with a mean submucosal
      tunneling length of(10.5 +/- 1.5)(range 8-15) cm. The average length of
      endoscopic myotomy of inner circular muscle was(9.5 +/- 2.5)(range 7-13) cm. No
      serious complications related to POEM were encountered. The median follow-up
      period was 2.5(range 1-6) months. Dysphagia symptom was relieved significantly
      during the follow-up period in 41 patients; one patient had dysphagia and
      vomiting 15 days after the operation. Endoscopic observation showed a submucosal
      fistula which was managed by endoscopic incision. CONCLUSIONS: As a novel
      minimally invasive therapy for AC, POEM appears to have definite short-term
      outcomes and can rapidly alleviate dysphagia symptom. Further observations and
      long follow-up are needed to evaluate long-term outcome and complications.

PMID- 21948539
TI  - [Risk factors of surgical interventions in patients with esophageal foreign
      bodies].
AB  - OBJECTIVE: To investigate the risk factors of surgical interventions in patients
      with esophageal foreign bodies(EFBs). METHODS: Forty-three cases with EFBs
      underwent surgical interventions from January 1962 to January 2011 in Department
      of Thoracic Surgery at the Tangdu Hospital were enrolled in the study group.
      Forty three cases with EFBs who received non-surgical treatment in the same
      hospital and during the same period matched by gender and age(the age difference
      between the paired patients was 5 years or less) were selected as the control
      group. Clinical data including type of EFBs, duration of impaction, location of
      EFBs, complications associated with EFBs were collected. Univariate and
      multivariate conditional logistic analysis were used for risk factors analysis.
      RESULTS: Univariate conditional logistic analysis showed that type of EFBs,
      duration of impaction, location of EFBs, and complications associated with EFBs
      were risk factors of surgical interventions in patients with EFBs(P<0.05).
      Further multivariate conditional logistic analysis showed that type of EFBs(sharp
      EFBs) was the independent factor of surgical interventions in patients with
      EFBs(P=0.043; OR=29.228, 95% CI:1.114-766.686). CONCLUSIONS: Physician should pay
      more attention to patients with sharp EFBs. Whether the patients need surgical
      interventions or not should base on factors including duration of impaction,
      location of EFBs, and complications associated with EFBs.

PMID- 21948540
TI  - [Characteristics and risk factors of lymph node metastases in esophageal
      carcinoma].
AB  - OBJECTIVE: To investigate the status of lymph node metastases (LNM) of esophageal
      carcinoma and to identify the risk factors. METHODS: Clinical data of 308
      patients who underwent esophagectomy with three-field lymphadenectomy during
      January 2006 and December 2010 were reviewed. Characteristics of LNM were
      studied. RESULTS: The average number of dissected lymph nodes was 35.6 +/- 14.5
      in 308 patients. There were 197 patients(64%) had LNM. Logistic regression
      analysis showed that lymphatic vessel invasion(P=0.019) and deep tumor
      invasion(P<0.001) were risk factors of LNM. The highest LNM site was paratracheal
      node(25.0%). The incidence of cervical LNM was 14.1% in the middle thoracic
      carcinoma, higher than that of upper thoracic (7.3%) and lower thoracic (8.3%).
      Rate of LNM was lower in upper thoracic carcinomas than that in middle or lower
      ones(P=0.001). No significant difference of LNM was found among upper, middle and
      lower thoracic carcinoma for cervical or thoracic nodes. Lymphatic vessel
      invasion(P<0.001) and metastases in paratracheal lymph nodes (P=0.014) were risk
      factors for cervical LNM. CONCLUSIONS: LNM of esophageal carcinoma can be found
      in both directions vertically and skipped metastasis. Paratracheal lymph nodes
      involvement is an indicator for cervical lymphadenectomy in thoracic esophageal
      carcinoma.

PMID- 21948541
TI  - [Impact of number and extent of lymph node metastasis on prognosis of thoracic
      esophageal cancer].
AB  - OBJECTIVE: To evaluate the influence of the number, station and field of
      metastatic lymph node on the prognosis of thoracic esophageal cancer and to
      investigate an ideal nodal staging method. METHODS: Clinicopathological and
      follow-up data of the 204 patients who underwent thoracic esophagectomy from June
      2001 to December 2009 were analyzed retrospectively and all the patients were re
      staged according to the 7th edition of the AJCC TNM staging system. Log-rank test
      was applied to perform survival analysis according to lymph node metastasis
      staging(number, station, and field), Cox proportional hazard model was used to
      screen risk factors. RESULTS: The follow-up rate was 93.1%(190/204). The median
      follow up time was 37.0(0-104) months. The overall and cancer-specific 5-year
      survival rates were 35.0% and 38.8%. When grouped according to the number of
      metastatic lymph node(0, 1-2, 3-6, >= 7), the 5-year survival rates of pN0, pN1,
      pN2 and pN3 were 47.8, 31.8%, 11.5% and 0 respectively(P=0.000). When grouped
      according to the number of stations of metastatic lymph node[N(0s), N(1s)(1
      station LN metastasis), N(>= 2s)(>= 2 stations LN metastasis)], the 5-year
      survival rates of N(0s), N(1s), N(>= 2s) were 47.8%, 31.5% and 11.3%
      respectively(P=0.000). When grouped according to the number of fields of
      metastatic lymph node, the 5-year survival rates of N0, 1 field, 2 fields and 3
      fields involvement were 47.8%, 34.2%, 12.1% and 0 respectively(P=0.000). Cox
      regression showed that the number of stations [P=0.043, RR(95% CI)=1.540(1.013
      2.342)], and the number of fields[P=0.010, RR(95%CI)=2.187(1.210-3.951)] of
      metastatic lymph node were the independent risk factors for survival.
      CONCLUSIONS: The extent of metastatic lymph node is an independent risk factor
      for the prognosis of esophageal cancer patients. Revision of the current N
      classification of TNM staging system according to the number of stations of
      metastatic lymph node may be more reasonable.

PMID- 21948542
TI  - [Expression of DNA methylation of APC in peripheral blood and tumor tissue in
      patients with esophageal squamous cell carcinoma].
AB  - OBJECTIVE: To investigate the relationship between methylation status of APC gene
      in both peripheral blood and tumor tissues and clinical-pathology characteristics
      in patients with esophageal squamous cell carcinoma(ESCC), and to study the
      dynamic change of APC methylation in peripheral blood in the perioperative
      period. METHODS: Real-time MSP technique was used to detect methylation status of
      APC in tumor tissues, adjacent normal tissues and peripheral blood on the day
      before the surgery, intraoperative, postoperative day 7 in 76 cases with ESCC.
      Sixty healthy volunteers matched by age and gender were randomly selected as
      controls. RESULTS: The methylation rate of APC in tumor tissue and peripheral
      blood was 44.74%(34/76) and 42.11%(32/76), respectively, which were significantly
      higher than that in adjacent normal tissue and controls [6.58%(5/76) and
      1.67%(1/60), P=0.000]. The methylation rates showed good agreement between tumor
      tissues and peripheral blood, which could be verified by ROC curve(A Zeta=0.849,
      P=0.000). APC methylation rate was significantly related to pathological staging,
      lymph node metastasis, depth of invasion, and invasion of nerve and vessel
      (P<0.05). The results demonstrated that family history of cancer was
      independently associated with APC methylation in peripheral blood(P<0.05). DNA
      methylation rates in peripheral blood showed an initial increase and then
      decreased in the preoperative period, intraoperative and postoperative.
      CONCLUSION: The methylation rates of APC among free DNA in peripheral blood in
      patients with ESCC reflect tumor progression, and decrease with the solid tumour
      resection.

PMID- 21948543
TI  - [Gene expression profiling study of HPV-16 positive and HPV-negative esophageal
      squamous cell carcinoma].
AB  - OBJECTIVE: To study the difference in gene expression between human
      papillomavirus (HPV)16-positive and HPV-negative esophageal squamous cell
      carcinoma(ESCC) . METHODS: Eight HPV 16-positive and seven HPV-negative ESCC
      specimens were evaluated by PCR. The samples were then determined for gene
      expression profiling using Solexa Sequencing Chip followed by bioinformatics
      analysis. RESULTS: A total of 796 differentially expressed genes between HPV 16
      positive and HPV-negative ESCC were observed. Among them, 366 were up-regulated
      while 430 were down-regulated. Functional classification and pathway analysis
      showed that the functions of these genes were mostly related to tumor morphology,
      immune, and inflammatory response, cellular growth and proliferation and cellular
      movement. Of these, factors related to immune and inflammation were the most
      representative. CONCLUSION: Differences in immunologic factors may be associated
      with HPV infection in esophageal cancer.

PMID- 21948544
TI  - A membrane-bound antiparallel dimer of rat islet amyloid polypeptide.

PMID- 21948546
TI  - Retinal pathway origins of the pattern electroretinogram (PERG).
AB  - PURPOSE: To determine retinal pathway origins of pattern electroretinogram (PERG)
      in macaque monkeys using pharmacologic dissections, uniform-field flashes, and
      PERG simulations. METHODS: Transient (2 Hz, 4 reversals/s) and steady state (8.3
      Hz, 16.6 reversals/s) PERGs and uniform-field ERGs were recorded before and after
      intravitreal injections of L-AP4 (not APB) (2-amino-4-phosphonobutyric acid, 1.6
      2.0 mM), to prevent ON pathway responses; PDA (cis-2,3-piperidinedicarboxylic
      acid, 3.3-3.8 mM), to block activity of hyperpolarizing second- and all third
      order retinal neurons; and TTX (tetrodotoxin, 6 MUM), to block Na+-dependent
      spiking. PERGs were also recorded from macaques with advanced unilateral
      experimental glaucoma, and were simulated by averaging ON and OFF responses to
      uniform-field flashes. RESULTS: For 2-Hz stimulation, L-AP4 reduced both negative
      and positive-going (N95 and P50) amplitudes in transient PERGs, and their
      counterparts, N2 and P1 in simulations, to half-amplitude. PDA eliminated N95 and
      N2, but increased P50 and P1 amplitudes, in that it enhanced b-waves. As
      previously reported, severe experimental glaucoma or TTX eliminated photopic
      negative responses, N95, and N2; glaucoma eliminated P50 and reduced P1
      amplitude; TTX reduced P50 and hardly altered P1. For 8.3-Hz stimulation, L-AP4
      eliminated the steady state PERG and reduced simulated PERG amplitude, whereas
      PDA enhanced both responses. TTX reduced PERG amplitude to less than half;
      simulations were less reduced. Blockade of all postreceptoral activity eliminated
      transient and steady state PERGs, but left small residual P1 in simulations.
      CONCLUSIONS: Transient PERG receives nearly equal amplitude contributions from ON
      and OFF pathways. N95 reflects spiking activity of ganglion cells; P50 reflects
      nonspiking activity as well. Steady state PERG, in contrast, reflects mainly
      spike-related ON pathway activity.

PMID- 21948545
TI  - Activation of OX40 prolongs and exacerbates autoimmune experimental uveitis.
AB  - PURPOSE: T cells are essential for the development of autoimmune uveitis.
      Although the costimulatory molecule OX40 promotes T-cell function and expansion,
      it is unclear whether OX40 is implicated in ocular inflammation. The purpose of
      this study was to examine the role of OX40 in uveitis. METHODS: Experimental
      autoimmune uveitis (EAU) was induced in B10.RIII mice by subcutaneous injection
      of interphotoreceptor retinoid-binding protein peptide 161-180 (IRBP(161-180)).
      Some mice received an intravenous administration of OX40-activating antibody on
      days 0 and 4 after IRBP(161-180) sensitization or on days 10 and 14 of uveitis
      onset. The severity of EAU was evaluated by histology at different time points.
      In addition, ocular inflammatory cytokine expression was determined by real time
      PCR, and peripheral activated CD4(+)CD44(+)CD62L(-) T cells and IL-7Ralpha
      expression were analyzed by flow cytometry. The activated CD4(+)CD44(+)
      lymphocytes were rechallenged with IRBP(161-180) in vitro to assess their antigen
      recall response. RESULTS: The authors demonstrated a marked OX40 expression by
      infiltrating lymphocytes in enucleated human eyes with end-stage inflammation. In
      addition, the administration of OX40-activating antibody prolonged and
      exacerbated the disease course of EAU. Moreover, activation of OX40 not only
      increased CD4(+)CD44(+)CD62L(-) lymphocyte number, it upregulated IL-7Ralpha
      expression in the activated T-cell population. Lastly, these cells exhibited a
      stronger interferon-gamma response to IRBP(161-180) restimulation in vitro.
      CONCLUSIONS: The results reveal a pathogenic role of OX40 in uveitis.
      Furthermore, the upregulation of IL-7R in CD4(+)CD44(+) lymphocytes suggests that
      the activation of OX40 promotes the generation or expansion of uveitogenic memory
      T cells.

PMID- 21948547
TI  - Anterior chamber angle imaging with swept-source optical coherence tomography: an
      investigation on variability of angle measurement.
AB  - PURPOSE: To evaluate the reproducibility of anterior chamber angle measurements
      obtained by swept-source optical coherence tomography (OCT) and to identify
      factors associated with its measurement variability. METHODS: One eye from each
      of 30 healthy subjects was randomly selected for anterior segment OCT imaging
      (Casia SS-1000 OCT; Tomey, Nagoya, Japan) in three separate visits within a week.
      The angle opening distance (AOD), the trabecular iris space area (TISA), and the
      trabecular-iris angle (TIA) at the superior (90 degrees ), nasal (0 degrees ),
      inferior (270 degrees ), and temporal (180 degrees ) angles were measured. The
      intraobserver and interobserver reproducibility coefficient (RC) and intraclass
      correlation coefficient (ICC) were calculated. Generalized linear latent and
      mixed modeling was used to examine the association between the variance of angle
      measurements and each of the following: angle width, pupil diameter, pupil
      diameter variance, iris thickness, iris thickness variance, axial length,
      anterior chamber depth, scan location, scleral spur visibility, and age. RESULTS:
      The intervisit, intraobserver RCs ranged between 0.140 mm and 0.252 mm for AOD,
      0.050 mm(2) and 0.090 mm(2) for TISA, and 7.7 degrees  and 9.5 degrees  for TIA,
      and the interobserver RCs were between 0.103 mm and 0.187 mm, 0.049 mm(2) and
      0.101 mm(2), and 8.5 degrees  and 13.7 degrees , respectively. The ICCs were all
      >=0.83. Increased iris thickness, increased iris thickness variance, angle
      measured at the superior and inferior quadrants, increased angle width, and long
      axial length were associated with increased variance of angle measurements.
      CONCLUSIONS: Although the swept-source OCT had high reproducibility for angle
      measurement, differences in iris thickness, angle width, measurement location,
      and axial length may influence its variability.

PMID- 21948548
TI  - Prototype of a nanostructured sensing contact lens for noninvasive intraocular
      pressure monitoring.
AB  - PURPOSE: To present the application of a new sensor based on a flexible, highly
      piezoresistive, nanocomposite, all-organic bilayer (BL) adapted to a contact lens
      (CL) for non-invasive monitoring intraocular pressure (IOP). METHODS: A prototype
      of a sensing CL, adapted to a pig eyeball, was tested on different enucleated pig
      eyes. A rigid, gas-permeable CL was designed as a doughnut shape with a 3-mm
      hole, where the BL film-based sensor was incorporated. The sensor was a
      polycarbonate film coated with a polycrystalline layer of the highly
      piezoresistive molecular conductor beta-(ET)2I3, which can detect deformations
      caused by pressure changes of 1 mm Hg. The pig eyeballs were subjected to
      controlled-pressure variations (low-pressure transducer) to register the
      electrical resistance response of the CL sensor to pressure changes. Similarly, a
      CL sensor was designed according to the anatomic characteristics of the eye of a
      volunteer on the research team. RESULTS: A good correlation (r2 = 0.99) was
      demonstrated between the sensing CL electrical response, and IOP (mm Hg) changes
      in pig eyes, with a sensitivity of 0.4 Omega/mm Hg. A human eye test also showed
      the high potential of this new sensor (IOP variations caused by eye massage,
      blinking, and eye movements were registered). CONCLUSIONS: A new nanostructured
      sensing CL for continuous monitoring of IOP was validated in an in vitro model
      (porcine eyeball) and in a human eye. This prototype has adequate sensitivity to
      continuously monitor IOP. This device will be useful for glaucoma diagnosis and
      treatment.

PMID- 21948549
TI  - ToF-SIMS analysis of dexamethasone distribution in the isolated perfused eye.
AB  - PURPOSE: To illustrate the ability of time-of-flight secondary ion mass
      spectrometry (ToF-SIMS) to characterize and demonstrate the spatial distribution
      of dexamethasone within ocular tissues. METHODS: Dexamethasone sodium phosphate
      was administrated to perfused and nonperfused ovine eyes via intravitreal
      injections. The vitreous humor, the lens, and the retina of the eyes were then
      removed and divided into front, middle, and back sections. ToF-SIMS analysis was
      performed on each cross-section of the vitreous humor using Bi(3+) cluster source
      and images of drug distribution within the sections generated. RESULTS: In the
      positive ion spectra, four key drug fragment peaks were identified and in the
      negative ion spectra, one key drug peak was identified. All five important drug
      peaks were successfully imaged in each tissue section and their distribution
      within the section illustrated. The drug was shown in the nonliving eye to move
      by diffusion alone, whereas in the living eye the drug was shown to distribute
      faster within the vitreous and penetrate through to the back of the retina and
      also into the lens. CONCLUSIONS: The results illustrate the ability of ToF-SIMS
      to characterize and provide spatial information about drug distribution within
      ocular tissues. Key differences in drug movement through the vitreous humor,
      toward both the anterior and the posterior tissues, in the living eye and the
      nonliving ovine eye were demonstrated, showing that dexamethasone sodium
      phosphate distribution through the vitreous is not determined by diffusion alone.

PMID- 21948550
TI  - Human corneal endothelial cells employ phosphorylation of p27(Kip1) at both Ser10
      and Thr187 sites for FGF-2-mediated cell proliferation via PI 3-kinase.
AB  - PURPOSE: FGF-2 stimulates cell proliferation of rabbit corneal endothelial cells
      (rCECs) by degrading the cyclin-dependent kinase inhibitor p27(Kip1) (p27)
      through its phosphorylation mechanism. The authors investigated whether the cell
      proliferation of human CECs (hCECs) is also induced by FGF-2 stimulation through
      the p27 phosphorylation pathway. METHODS: Expression and activation of protein
      were analyzed by immunoblotting. Cell proliferation was measured by 3-(4,5
      dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay. Transfection of
      hCECs with small interference RNA (siRNA) was performed using a transfection
      reagent. RESULTS: FGF-2 stimulated cell proliferation in hCECs; the FGF-2 action
      was completely blocked by pathway-specific inhibitors for PI 3-kinase (LY294002)
      and MEK1/2 (U0126), respectively. Using immunoblotting, the authors showed that
      FGF-2 induced phosphorylation of p27 at both serine 10 (Ser10) and threonine 187
      (Thr187) sites. These effects were also completely blocked by LY294002 or U0126.
      The authors then determined cross-talk between PI 3-kinase and extracellular
      signal-regulated kinase (ERK)1/2; blocking of ERK1/2 activation by LY294002
      indicated that in hCECs ERK1/2 works as a downstream effector to PI 3-kinase for
      cell proliferation induced by FGF-2, whereas the ERK1/2 pathway in rCECs is
      parallel to the PI 3-kinase pathway. However, the downstream mechanism involved
      in cell cycle progression in hCECs is identical to that of rCECs: phosphorylation
      of p27 at Ser10 was mediated by kinase-interacting stathmin (KIS), confirmed with
      siRNA to KIS, and phosphorylation of p27 at Thr187 was mediated by cell division
      cycle 25A (Cdc25A), confirmed using Cdc25A inhibitor. CONCLUSIONS; FGF-2
      stimulates proliferation of hCECs through PI 3-kinase and its downstream target
      ERK1/2 pathways. This linear signal transduction significantly downregulates p27
      through its phosphorylation at both Ser10 and Thr187 sites mediated by KIS and
      Cdc25A, respectively.

PMID- 21948551
TI  - Miniaturized high-intensity focused ultrasound device in patients with glaucoma:
      a clinical pilot study.
AB  - PURPOSE: To evaluate the relative safety and potential efficacy of high-intensity
      focused ultrasound cyclocoagulation by a miniaturized annular device containing
      six piezoceramic transducers in patients with refractory glaucoma. METHODS: This
      was a three-center prospective interventional pilot study. Twelve eyes of 12
      patients with refractory glaucoma were insonified using a ring-shaped probe
      containing six miniaturized high-frequency transducers operating at 21 MHz.
      Ultrasound biomicroscopy (UBM) and a complete ophthalmic examination were
      performed before the procedure and at 1 day, 1 week, 1 month, and 3 months after
      the procedure. Additional visits were performed 6 and 12 months after the
      procedure. RESULTS: Intraocular pressure was significantly reduced (P < 0.01)
      from a mean preoperative value of 37.9 +/- 10.7 mm Hg to a mean postoperative
      value of 27.3 +/- 12.4, 25.2 +/- 11.3, 25.2 +/- 7.7, 24.8 +/- 9.8, and 26.3 +/-
      5.1 mm Hg at 1 day, 1 week, 1 month, 3 months, and 6 months, respectively, and to
      a mean value of 24.7 +/- 8.5 at the last follow-up visit. No major intraoperative
      or postoperative complications occurred. Minor postoperative corneal
      complications developed in four patients with previous corneal abnormalities:
      superficial punctate keratitis (n = 3) and central superficial corneal ulceration
      (n = 1). UBM showed cystic involution of the ciliary body in 9 of the 12 eyes and
      a suprachoroidal fluid space in 8 of the 12 eyes. CONCLUSIONS: Ultrasonic
      circular cyclocoagulation using high-intensity focused ultrasound delivered by a
      circular miniaturized device containing six piezoceramic transducers seems to be
      an effective and well-tolerated method to reduce intraocular pressure in patients
      with refractory glaucoma.

PMID- 21948553
TI  - Soluble Nogo-66 receptor prevents synaptic dysfunction and rescues retinal
      ganglion cell loss in chronic glaucoma.
AB  - PURPOSE: Myelin inhibitory proteins inhibit axon growth and synaptic function by
      binding to the Nogo-66 receptor (NgR)1 in the central nervous system. Glaucoma is
      a progressive neuropathy characterized by loss of vision as a result of retinal
      ganglion cell (RGC) death. Synaptic degeneration is thought to be an early
      pathology of neurodegeneration in glaucoma and precedes RGC loss. The authors
      aimed to examine whether the NgR1 antagonist promotes synaptic recovery and RGC
      survival in glaucoma. METHODS: Experimental ocular hypertension model was induced
      in adult rats with laser coagulation of the episcleral and limbal veins. NgR1
      antagonist, soluble NgR1 (sNgR-Fc) was administrated to examine their effect on
      synaptic recovery and RGC survival. Expression of c-Fos, a neuronal connectivity
      marker, in the retinas was investigated using immunohistochemistry. RESULTS: NgR1
      was expressed in RGCs and upregulated after intraocular pressure elevation.
      Treatment with sNgR-Fc significantly reduced RGC loss at 2 and 4 weeks after the
      induction of ocular hypertension and also promoted RGC survival after optic nerve
      transection. There was no RGC loss at 5 days but there was significant synaptic
      degeneration as measured by c-Fos. Administration of sNgR-Fc attenuated synaptic
      degeneration at 5 days, and at 2 and 4 weeks. CONCLUSIONS: These data suggest
      that synaptic degeneration may be an initial molecular mechanism for
      neurodegeneration in glaucoma and appropriate NgR1 antagonism may delay the
      progression of the disease.

PMID- 21948552
TI  - The structure and function of the macula in patients with advanced retinitis
      pigmentosa.
AB  - PURPOSE: To assess the structure and function of the macula in advanced retinitis
      pigmentosa (RP). METHODS: Twenty-nine eyes of 22 patients with RP were compared
      against 17 control eyes. Time-domain optical coherence tomography (OCT) data were
      processed using OCTRIMA (optical coherence tomography retinal image analysis) as
      a means of quantifying commercial OCT system images. The thickness of the retinal
      nerve fiber layer (RNFL), ganglion cell layer and inner plexiform layer complex
      (GCL+IPL), inner nuclear layer and outer plexiform layer complex (INL+OPL), and
      the outer nuclear layer (ONL) were measured. Multifocal electroretinography
      (mfERG) was performed; two groups were formed based on the mfERG findings.
      Fourteen eyes had no detectable central retinal function (NCRF) on mfERG;
      detectable but abnormal retinal function (DRF) was present in the mfERG of the
      other 15 eyes. RESULTS: The thickness of the ONL in the central macular region
      was significantly less in the NCRF eyes compared with that in both DRF eyes and
      controls. The ONL was significantly thinner in the pericentral region in both
      patient groups compared with that in controls, whereas the thickness of the
      GCL+IPL and INL+OPL was significantly decreased only in the NCRF eyes. The RNFL
      in the peripheral region was significantly thicker, whereas the thickness of the
      GCL+IPL and ONL was significantly thinner in both patient groups compared with
      that in controls. CONCLUSIONS: The results are consistent with degeneration of
      the outer retina preceding inner retinal changes in RP. OCT image segmentation
      enables objective evaluation of retinal structural changes in RP, with potential
      use in the planning of therapeutic interventions and conceivably as an outcome
      measure.

PMID- 21948554
TI  - Lentiviral vector-mediated PAX6 overexpression promotes growth and inhibits
      apoptosis of human retinoblastoma cells.
AB  - PURPOSE: The cancer-associated gene PAX6 is a key regulator in the embryological
      development of the retina. The authors assessed whether PAX6 was associated with
      the development of retinoblastoma. Methods. Two human retinoblastoma cell lines
      (Y79 and SO-Rb50) were transfected with PAX6-GFP recombinant lentiviral vectors
      and were compared with cells undergoing transfection with GFP lentiviral vectors
      and cells without any intervention. Overexpression of PAX6 was assessed by
      quantitative real-time polymerase chain reaction analysis and Western blot
      analysis. Cell proliferation assays were evaluated by colorimetric cell counting
      kit-8. The cell cycle was analyzed by fluorescence-activated cell sorting (FACS).
      Apoptosis rates were assessed by TUNEL assay followed by FACS analysis. Using
      Western blot analysis, the authors measured levels of proteins p53, p21, p27,
      cdc2, proliferating cell nuclear antigen, and cleaved caspase-3. RESULTS: Three
      days after transfection, both cell lines showed a statistically significant (P <
      0.001) overexpression of PAX6, parallel to significantly (P < 0.001) increased
      cell proliferation. At 7 days after transfection, cell cycle analysis showed a
      significant (P < 0.001) reduction of G0/G1 arrest and a significant induction of
      G2/M arrest (P < 0.01). Parallel to a reduction in caspase-3 levels, the
      apoptosis rate significantly (P < 0.001) decreased. Levels of p53, p21, and p27
      were reduced, and the levels of cdc2 were increased. CONCLUSIONS: Lentiviral
      vector-mediated overexpression of PAX6 in human retinoblastoma cells was
      associated with increased cell proliferation parallel to a reduced caspase-3
      dependent apoptotic rate and a change in the p53 regulated cell cycle. PAX6 may
      be further explored for the diagnosis of and therapy for retinoblastomas.

PMID- 21948555
TI  - Logarithmic transformation of spectral-domain optical coherence tomography data
      in uveitis-associated macular edema.
AB  - PURPOSE: To determine the utility of logarithmic transformation of spectral
      domain optical coherence tomography (logSD-OCT) retinal thickness data for
      assessment of clinically meaningful changes in uveitis-associated macular edema.
      METHODS: Patients with noninfectious uveitis-associated macular edema at our
      institution between August 2010 and March 2011 were identified. Only those with
      SD-OCT imaging were included. The clinical diagnoses, visual acuities, and
      central subfield thickness (CST) measurements were recorded. Logarithmic
      transformation of the retinal thickness was performed and frequency histograms
      plotted. A linear mixed-effects model of the logarithm minimum angle of
      resolution (logMAR) visual acuity on logSD-OCT was created to account for within
      patient correlation among visits and between eyes. RESULTS: A total of 98 SD-OCT
      images from 34 patients were analyzed. The mean age at examination was 40 years
      (range, 11-69 years). Anatomic diagnoses included anterior/intermediate uveitis
      (23%), intermediate uveitis (21%), posterior uveitis (12%), and panuveitis (44%).
      LogSD-OCT data provided a more normal distribution than standard CST. Skewness
      and kurtosis of CST data were 1.04 and 0.37, respectively, and skewness and
      kurtosis of logSD-OCT data were 0.40 and -0.48, respectively. There was a
      positive correlation between logSD-OCT and logMAR visual acuity. Specifically,
      for each 0.1-unit increase in logSD-OCT, the logMAR visual acuities increased
      (worsened) by 0.082 units (95% CI: 0.057-0.107, P < 0.001). CONCLUSIONS:
      Logarithmic transformation of SD-OCT measurements provided a more normal
      distribution and positively correlated with logMAR visual acuity. This
      transformation of retinal thickness may be valuable for assessing clinically
      significant changes in SD-OCT measurements in future uveitis studies.

PMID- 21948556
TI  - Measurement of the limbus-insertion distance in adult strabismus patients with
      anterior segment optical coherence tomography.
AB  - PURPOSE: To determine the ability of the anterior segment optical coherence
      tomography (AS-OCT) in measuring the distance from the corneoscleral limbus to
      the insertion site of the horizontal extraocular muscles in adult patients with
      strabismus. METHODS: A total of 16 strabismus patients were recruited for this
      study. The limbus-insertion distances of the horizontal rectus muscles were
      measured with AS-OCT preoperatively and calipers intraoperatively. The intraclass
      correlation coefficient (ICC), Pearson's correlation coefficients, and Bland
      Altman plots were used to evaluate the degree of agreement between the two
      methods of measurements. RESULTS: Measurements of the limbus-insertion distances
      were taken on 37 muscles of the 16 patients: 18 medial rectus (MR) and 19 lateral
      rectus (LR). The mean limbus-insertion distance of MR and LR measured
      intraoperatively were 5.32 +/- 0.44 mm (range, 4.5-6.1 mm) and 6.58 +/- 0.53 mm
      (range, 5.5-7.5 mm). Comparable results measured with the AS-OCT were 5.72 +/-
      0.60 mm (range, 4.62-6.82 mm) and 6.80 +/- 0.61 mm (range, 5.8-7.86 mm). For MR
      group and LR group, the values of limbus-insertion distance showed high Pearson's
      correlation coefficients (0.729 and 0.786, respectively). With the ICC analysis
      excellent agreement was observed for the measurements of LR group (ICC = 0.75).
      Fair to good agreement was observed for the MR group (ICC = 0.61). Bland-Altman
      plots also showed good agreement between the two methods of measurements.
      CONCLUSIONS: AS-OCT can image the structure of horizontal rectus muscles well and
      provide good reliability and accuracy in measurement of the limbus-insertion
      distance.

PMID- 21948557
TI  - Laser microstructuring of photomodified fluorinated ethylene propylene surface
      for confined growth of Chinese hamster ovary cells and single cell isolation.
AB  - We present a method for laser lithography of cell-adhesive arrays on a
      fluoropolymer surface. The method is based on 172 nm excimer-lamp
      photomodification in ammonia atmosphere followed by microstructuring by laser
      ablation. The improved wettability of the polymer is caused by new chemical
      groups on the surface after the UV treatment that we proved by Fourier transform
      infrared spectroscopy and X-ray photoelectron spectroscopy analyses. The cell
      adhesion properties of micropatterned structures were tested by cultivation of
      mammalian cells. We show that single elongated cells can grow confined to lines
      with sharply defined boundaries of the cell-covered areas. In preliminary
      experiments, we also demonstrate that the described technique allows the
      production of single-cell arrays with variable cell shape.

PMID- 21948558
TI  - Direct reprogramming of melanocytes to neural crest stem-like cells by one
      defined factor.
AB  - Mouse and human somatic cells can either be reprogrammed to a pluripotent state
      or converted to another lineage with a combination of transcription factors
      suggesting that lineage commitment is a reversible process. Here we show that
      only one factor, the active intracellular form of Notch1, is sufficient to
      convert mature pigmented epidermal-derived melanocytes into functional
      multipotent neural crest (NC) stem-like cells. These induced NC stem cells
      (iNCSCs) proliferate as spheres under stem cell media conditions, re-express NC
      related genes, and differentiate into multiple NC-derived mesenchymal and
      neuronal lineages. Moreover, iNCSCs are highly migratory and functional in vivo.
      These results demonstrate that mature melanocytes can be reprogrammed toward
      their primitive NC cell precursors through the activation of a single stem cell
      related pathway. Reprogramming of melanocytes to iNCSCs may provide an alternate
      source of NCSCs for neuroregenerative applications.

PMID- 21948559
TI  - Continuity of care for people with psychotic illness: its relationship to
      clinical and social functioning.
AB  - BACKGROUND: The relationship between continuity of care and user characteristics
      or outcomes has rarely been explored. The ECHO study operationalized and tested a
      multi-axial definition of continuity of care, producing a seven-factor model used
      here. AIMS: To assess the relationship between user characteristics and
      established components of continuity of care, and the impact of continuity on
      clinical and social functioning. METHODS: The sample comprised 180 community
      mental health team users with psychotic disorders who were interviewed at three
      annual time-points, to assess their experiences of continuity of care and
      clinical and social functioning. Scores on seven continuity factors were tested
      for association with user-level variables. RESULTS: Improvement in quality of
      life was associated with better Experience & Relationship continuity scores
      (better user-rated continuity and therapeutic relationship) and with lower
      Meeting Needs continuity factor scores. Higher Meeting Needs scores were
      associated with a decrease in symptoms. CONCLUSION: Continuity is a dynamic
      process, influenced significantly by care structures and organizational change.

PMID- 21948560
TI  - Extensive variation and low heritability of DNA methylation identified in a twin
      study.
AB  - Disturbance of DNA methylation leading to aberrant gene expression has been
      implicated in the etiology of many diseases. Whereas variation at the genetic
      level has been studied extensively, less is known about the extent and function
      of epigenetic variation. To explore variation and heritability of DNA
      methylation, we performed bisulfite sequencing of 1760 CpG sites in 186 regions
      in the human major histocompatibility complex (MHC) in CD4+ lymphocytes from 49
      monozygotic (MZ) and 40 dizygotic (DZ) twin pairs. Individuals show extensive
      variation in DNA methylation both between and within regions. In addition, many
      regions also have a complex pattern of variation. Globally, there appears to be a
      bimodal distribution of DNA methylation in the regions, but a significant
      fraction of the CpG sites are also heterogeneously methylated. Classification of
      regions into CpG islands (intragenic and intergenic), 5' end of genes not
      associated with a defined CpG island, conserved noncoding regions, and random CpG
      sites shows region-type differences in variation and heritability. Analyses
      revealed slightly lower intra-pair differences among MZ than among DZ pairs,
      suggesting some genetic influences on DNA methylation variation, with most of the
      variance attributed to nongenetic factors. Overall, heritability estimates of DNA
      methylation were low. Our heritability estimates are, however, somewhat deflated
      due to the presence of batch effects that artificially inflate the estimates of
      shared environment.

PMID- 21948561
TI  - Beta2-agonists use during pregnancy and the risk of congenital malformations.
AB  - BACKGROUND: Treatment of asthma symptoms during pregnancy is crucial for maternal
      and fetal health. Short-acting beta2-agonists (SABA) are frequently used as
      rescue medications and long-acting beta2-agonists (LABA) are used as add-on
      controller therapy for asthma during pregnancy. OBJECTIVE: The objective of this
      study was to investigate the association between exposure to SABA and LABA in the
      first trimester of pregnancy and the risk of congenital malformations among women
      with asthma. METHODS: A cohort of pregnancies from women with asthma was formed
      through linkage of three administrative databases from Quebec, Canada. The
      primary outcomes were major and any congenital malformations. The primary
      exposures were exposure to SABA and LABA during the first trimester, while
      secondary exposure was weekly SABA doses. The associations between congenital
      malformations (any, major, and specific) and SABA and LABA exposure were assessed
      with generalized estimating equations models. RESULTS: From a group of 13,117
      pregnancies, we identified 1242 and 762 infants with any (9.5%) and major (5.8%)
      congenital malformations, respectively. The adjusted odds ratios (95% confidence
      interval [CI]) for any malformations associated with the use of SABA and LABA
      were 1.04 (95% CI, 0.92-1.17) and 1.37 (95% CI, 0.92-2.17), respectively. The
      corresponding figures were 0.93 (95% CI, 0.80-1.08) and 1.31 (95% CI, 0.74-2.31)
      for major malformations. Significant increased risks of major "cardiac" and major
      "other and unspecified" congenital malformations were observed with LABA use.
      CONCLUSION: Our study supports the evidence of SABA safety during pregnancy, but
      more research is required to assess whether the increased risk of malformations
      among LABA users is due to the medication, bias by asthma severity, or chance
      alone.

PMID- 21948562
TI  - Programming the cellular uptake of physiologically stable peptide-gold
      nanoparticle hybrids with single amino acids.

PMID- 21948563
TI  - Phosphoinositide 3-kinase inhibition enables retinoic acid-induced neurogenesis
      in monolayer culture of embryonic stem cells.
AB  - Retinoic acid (RA) is able to induce the differentiation of embryonic stem cells
      into neuronal lineages. The mechanism of this effect is unknown but it has been
      evidenced to be dependent on the formation of floating spheroids called embryoid
      bodies. Results presented here show that the inhibition of phosphoinositide 3
      kinase signaling pre-determines mouse embryonic stem cells to RA induced
      neurogenesis in monolayer culture with no need of embryoid bodies formation.

PMID- 21948564
TI  - MicroRNA-451 is involved in the self-renewal, tumorigenicity, and chemoresistance
      of colorectal cancer stem cells.
AB  - Many antitumor therapies affect rapidly dividing cells. However, tumor
      proliferation may be driven by cancer stem cells (CSCs), which divide slowly and
      are relatively resistant to cytotoxic drugs. Thus, many tumors may progress
      because CSCs are not sensitive to the treatment. In this work, we searched for
      target genes whose expression is involved in proliferation and chemoresistance of
      CSCs. Both of these processes could be controlled simultaneously by cell
      regulators such as microRNAs (miRNAs). Therefore, colonospheres with properties
      of CSCs were obtained from different colon carcinoma cells, and miRNA profiling
      was performed. The results showed that miR-451 was downregulated in colonspheres
      versus parental cells. Surprisingly, expression of miR-451 caused a decrease in
      self-renewal, tumorigenicity, and chemoresistance to irinotecan of colonspheres.
      We identified cyclooxygenase-2 (COX-2) as an indirect miR-451 target gene
      involved in sphere growth. Our results indicate that miR-451 downregulation
      allows the expression of the direct target gene macrophage migration inhibitory
      factor, involved in the expression of COX-2. In turn, COX-2 allows Wnt
      activation, which is essential for CSC growth. Furthermore, miR-451 restoration
      decreases expression of the ATP-binding cassette drug transporter ABCB1 and
      results in irinotecan sensitization. These findings correlate well with the lower
      expression of miR-451 observed in patients who did not respond to irinotecan
      based first-line therapy compared with patients who did. Our data suggest that
      miR-451 is a novel candidate to circumvent recurrence and drug resistance in
      colorectal cancer and could be used as a marker to predict response to irinotecan
      in patients with colon carcinoma.

PMID- 21948565
TI  - Fascin expression and its potential significance in gastrointestinal stromal
      tumors.
AB  - BACKGROUND/AIMS: Fascin is an actin-bundling protein that is important in cell
      motility. Fascin expression has been shown to have a potential role in tumor
      progression for some epithelial tumors. However, there are only a few studies
      related to its expression in mesenchymal tumors. We investigated fascin
      expression in gastrointestinal stromal tumors. METHODS: Thirty gastrointestinal
      stromal tumors, which were very low (n=6), low (n=2), moderate (n=4), and high
      (n=18) risk, constituted our series. Immunohistochemical expression of fascin was
      studied in all cases. RESULTS: Immunoreactivity was observed in only five cases,
      all of which were in the high-risk group. The remaining cases (25/30) showed no
      immunoreactivity, and the difference did not seem statistically important
      (p=0.261). Fascin expression was stronger in epithelioid cells than spindle
      shaped cells (p=0.003). In addition, gastrointestinal stromal tumors in the small
      bowel showed higher fascin expression than those in the other localizations
      (p=0.043). CONCLUSIONS: It seems that anatomic localization and the tumor cell
      type of gastrointestinal stromal tumors show statistically significant
      differences with regard to fascin expression. Although our series is limited, we
      think that fascin should be considered as a marker that is worthy of further
      study for its potential usage as a prognostic indicator in gastrointestinal
      stromal tumors.

PMID- 21948566
TI  - Normal defecation pattern, frequency of constipation and factors related to
      constipation in Turkish children 0-6 years old.
AB  - BACKGROUND/AIMS: The aim of this study is to figure out defecation features,
      constipation frequency, reasons and factors effecting on functional constipation
      in 0-6 years old children. MATERIAL AND METHODS: This descriptive study had been
      carried out in Gazi University School of Medicine Pediatric polyclinics between
      February-June 2007 and 1018 children aged 0-6 years were included. The study
      comprises data about defecation pattern and prevalence of constipation. Children
      were divided into five groups according to the age. Their parents were asked to
      complete a structured questionnaire. Physical examinations, stool frequency
      according to the age, feeding patterns, age and gender distributions, major
      complaints and associated factors were all investigated. RESULTS: Among 1018
      children there were 526 (51.7%) boys and 492 (48.3%) girls. One hundred ninety
      five (88.2%) infants were exclusively breastfed, 42 children (17.8%) were getting
      additional feeding in 0-6 months age group. Forty-eight of 1018 children (4.7%)
      were diagnosed as constipated. Twenty-eight (58.3%) were male and 20 (41.7%) were
      female. Parents of the constipated children defined the major complaints with
      defecation as discomfort (33%), pain (25%), seldom defecation (21%), hard stools
      (17%) and rectal bleeding (4%). Eighteen parents (37.5%) thought that
      constipation is related to dietary type. Refraining from school toilet was
      defined by seven parents (14.6%). CONCLUSION: Constipation may predict serious
      organic problems in newborns; however organic problems are not encountered in 95%
      of bigger children. These cases are described as functional constipation. Dietary
      factors and refraining from school toilets have to be considered during
      treatment.

PMID- 21948567
TI  - Therapeutic effects of four molecular-weight fractions of Kurozu against dextran
      sulfate sodium-induced experimental colitis.
AB  - BACKGROUND/AIMS: Kurozu has been reported to ameliorate colitis in mice and to
      have an anti-oxidative effect. However, the active components and mechanism of
      action remain unknown. Here, as a first step to identify the active components,
      we chromatographically fractionated Kurozu and investigated the anti-colitis
      activity of the fractions, focusing on anti-nitration activity. METHODS: Kurozu
      was divided into 4 molecular-weight fractions (fraction I, >4,000 daltons; II,
      2,000~4,000 daltons; III, 800~2,000 daltons; IV, <800 daltons). Forty C57black6
      mice were divided into 5 groups as follows: the control group received standard
      CE-2 diet, and Groups I~IV received CE-2 diet containing Kurozu fractions I~IV,
      respectively. Dextran sulfate sodium was administered to the mice for 12 days to
      induce colitis. Body weight and bloody stool frequency were monitored as indices
      of severity of colitis after administration of dextran sulfate sodium, and at 12
      days, all mice were sacrificed for examination of colonic pathology and
      nitrotyrosine production in the colon tissues. RESULTS: Colitis was markedly
      ameliorated in Group III, followed by Group II, while Group IV showed little
      difference from the control. The colonic nitrotyrosine level in Group III was
      significantly reduced compared with the control. CONCLUSIONS: The major
      protective components in Kurozu appear to have molecular weights in the range of
      800~4,000 daltons, and their action appears to be related, at least in part, to
      anti-oxidative and anti-nitration effects.

PMID- 21948568
TI  - Extension of ulcerative colitis.
AB  - BACKGROUND/AIMS: It is known that ulcerative proctitis might show extension, but
      in practice, patients with proctitis are not considered as important with regard
      to regular follow-up and treatment. The aim of this study was to evaluate the
      extension of ulcerative colitis cases limited to the rectum and compare them with
      the patients with rectosigmoid and left colonic ulcerative colitis for their
      features, risk factors influencing the extension and natural course of the
      disease. METHODS: The study involved 193 (62 rectal, 49 rectosigmoid and 82 left
      sided) ulcerative colitis patients. RESULTS: Fourteen percent of the patients
      showed extension to at least one proximal segment in 3.9+/-2.9 (range: 0.8-12)
      years. The extension was found as 16.1% in proctitis, 12.2% in rectosigmoiditis
      and 13.4% in left-sided colitis groups. Extension was found 2.79-fold (95%
      confidence interval: 1.1-7.1) higher in patients with chronic active disease.
      Further, the patients with amoebic attacks, those under steroid treatment and
      those without treatment showed higher risk for extension. CONCLUSIONS: Patients
      with proctitis, like the patients presenting with more extensive colitis, should
      be offered regular treatment and follow-up.

PMID- 21948569
TI  - Does glucagon like peptide-2 receptor expression have any effect on the
      development of human colorectal cancer?
AB  - BACKGROUND/AIMS: Glucagon like peptide-2 may play an important role in human
      colon cancer and polyp development because of its proliferative and
      antiapopitotic effects especially in colon. In this study, we investigated the
      role of human glucagon like peptide and it's receptor in development of human
      colorectal carcinogenesis. MATERIAL AND METHODS: The study includes 30 patients
      in colon cancer group and 20 patients in colonic polyp group who have been
      diagnosed by endoscopic and pathologic examination in Dokuz Eylul University,
      Department of Gastroenterology within 2 year-period. For comparison biopsies were
      taken from normal appearing colonic mucosa of the same patient. The cancer, polyp
      and normal colon mucosa samples were stained with glucagon like peptide receptor
      antibody by immunohistochemical method. RESULTS: Glucagon like peptide 2 receptor
      positivity of colon cancer patients was 20 % (6/30) in focal cytoplasmic
      coloration while it was 0 % in colonic adenomas and 100 % in enteroendocrine
      cells of normal colonic mucosa. Statistically significant differences were found
      by the comparison of colonic polyp and normal colonic tissue (p=0.000), colonic
      cancer and normal colonic tissue (p=0.000) and colonic polyp and cancer tissues
      (p= 0.023). CONCLUSION: Glucagon like peptide-2 receptor expression in colonic
      adenomas was not detected in human in contrary to the study on mice. Our study
      suggested that Glucagon like peptide-2 receptor expression is not a factor in
      adenoma-cancer pathogenesis. More studies are needed on this subject with more
      facts and different methods.

PMID- 21948570
TI  - A new risk factor for the development of non-alcoholic fatty liver disease: HLA
      complex genes.
AB  - BACKGROUND/AIMS: Several studies have emphasized the role of genetic factors in
      susceptibility to non-alcoholic fatty liver disease. The aim of this study was to
      examine the possible influence of human leukocyte antigen in the development of
      non-alcoholic fatty liver disease. METHODS: Between January 2000 and January
      2008, data of 655 donor candidates were examined from routinely performed
      abdominal ultrasonography and for aspartate aminotransferase, alanine
      aminotransferase, hepatitis B virus, hepatitis C virus, cytomegalovirus, human
      immunodeficiency virus, hepatic functions, and human leukocyte antigen class I
      and II antigens; data of 116 healthy candidates were also included in this study.
      To reduce the influence of possible confounding factors, we excluded diseases
      known to be associated with non-alcoholic fatty liver disease like obesity,
      diabetes mellitus, coronary artery disease, hyperlipidemia, and metabolic
      syndrome. Non-alcoholic fatty liver disease was diagnosed in 66 individuals (33
      male, median age: 53.8 [range, 32-77 years]) by means of ultrasonography data,
      and 50 individuals, whose ultrasonography data did not show hepatosteatosis,
      comprised the control group (20 male, median age: 44.6 [range, 26-71 years]).
      RESULTS: Human leukocyte antigen-B65 (28.8% vs 0%, p<0.001) and DQ5 (40.7% vs
      16.1%, p<0.05) were found to be expressed significantly more in non-alcoholic
      fatty liver disease compared with controls. Serum alanine aminotransferase (27.1
      IU/L vs 20 IU/L, p<0.05) was significantly higher in the study group.
      CONCLUSIONS: Our preliminary study suggests that human leukocyte antigen plays a
      role in the pathogenesis of non-alcoholic fatty liver disease; however, more
      studies are needed to clarify these data.

PMID- 21948571
TI  - Vitamin D ameliorates stress ligand expression elicited by free fatty acids in
      the hepatic stellate cell line LX-2.
AB  - BACKGROUND/AIMS: Hepatic stellate cells play an important role as the major
      source of fibrillar and non-fibrillar matrix proteins in the process of liver
      fibrosis. Natural killer cells have an anti-fibrotic effect through the killing
      of activated hepatic stellate cells. Major histocompatibility complex class I
      related molecules, MICA and MICB, function as ligands for the NKG2D receptor and
      play an important role in hepatic stellate cells susceptibility to natural killer
      cells during hepatic inflammation. The aim of this study was therefore to
      investigate the effect of vitamin D2 and free fatty acids on stress ligands and
      pro-fibrotic activity in LX-2 cells and human primary hepatic stellate cells.
      METHODS: LX-2 cells and primary human hepatic stellate cells were treated with
      vitamin D2 (10-6 M) and free fatty acids at different concentrations (0.25 mM,
      0.5 mM, and 1 mM) for 24 hours, and expressions of the stress ligands MICA/B as
      well as of transforming growth factor-beta, alpha-smooth muscle actin and
      collagen 1alpha were assessed by quantitative real time-polymerase chain
      reaction. RESULTS: Treatment of cells with 0.5 mM and 1 mM free fatty acids
      induced alpha-smooth muscle actin and transforming growth factor-beta expression
      in LX-2 cells. Moreover, 1 mM free fatty acids resulted in increased expression
      of MICA. Surprisingly, collagen 1alpha expression was reduced after addition of
      free fatty acids. MICA/B expression in primary hepatic stellate cells was not
      affected by free fatty acids treatment. Vitamin D2 treatment significantly
      downregulated the free fatty acids-induced expression of transforming growth
      factor-beta and alpha-smooth muscle actin in LX-2 cells. Further, in hepatic
      stellate cells, a significant decrease in MICA/B mRNA with vitamin D2,
      independent of free fatty acids treatment, was detectable. CONCLUSIONS: These
      results indicate that vitamin D2 may reduce inflammatory and pro-fibrogenic
      activity of stellate cells in vitro.

PMID- 21948572
TI  - Effects of lycopene on oxidative stress and remnant liver histology after partial
      hepatectomy in rats.
AB  - BACKGROUND/AIMS: Partial hepatectomy is performed for the treatment of mass
      lesions in the liver. Lycopene, which is a carotenoid, is present in various
      physiologic processes. In this study, the effects of lycopene administration in
      partially hepatectomized rats were evaluated by assessing various
      oxidant/antioxidant parameters, remnant liver histology and plasma nitric oxide
      levels. METHODS: Thirty Wistar albino adult male rats were randomly divided into
      three equal groups as: Sham, Partial Hepatectomy and Lycopene-Administered +
      Partial Hepatectomy groups. Lycopene (4 mg/kg), which was dissolved in olive oil,
      was given to the rats per orally (via gavage tube) (0.1 ml) every day for 6 weeks
      before partial hepatectomy and for one week after partial hepatectomy. Tissue and
      blood samples were collected one week after partial hepatectomy. RESULTS: Plasma
      malondialdehyde (p<0.001) and nitric oxide (p<0.05) levels in the lycopene
      administered + partial hepatectomy group were significantly higher than in the
      partial hepatectomy group. Intraerythrocytic glutathione (p<0.001), plasma
      (p<0.001) and liver tissue Cu-Zn (p<0.05) superoxide dismutase levels of the
      lycopene-administered + partial hepatectomy group were significantly lower than
      in the partial hepatectomy group. CONCLUSIONS: Lycopene administration could be
      harmful by increasing oxidative stress after partial hepatectomy.

PMID- 21948573
TI  - Diffuse and psammomatous calcification in intestinal type gastric carcinoma:
      report of two cases with literature review.
AB  - Psammoma bodies are round, concentrically laminated calcospherites ranging from 5
      to 100 MUm in diameter. They may indicate certain types of tumors including
      papillary carcinoma of the thyroid, meningioma and papillary serous tumors of the
      ovary, and to a lesser extent may be found in leiomyomas and angiomas of the
      gastrointestinal tract. Dystrophic calcification is uncommon in gastric cancer
      and displays either diffuse or psammomatous pattern. Diffuse type calcification
      is generally seen within the pools of mucin in advanced mucinous adenocarcinoma.
      Conversely, psammomatous calcification is associated with non-mucinproducing
      carcinomas and detected not only within the carcinomatous glandular lumina but
      also in the stroma. Total gastrectomy specimens of a 74-year-old male and a 54
      year-old female with moderately differentiated intestinal type adenocarcinomas
      revealed diffuse and psammomatous calcification, respectively. Although diffuse
      type calcification is well-documented, to date it has not been reported in non
      mucin-producing intestinal gastric carcinoma. Moreover, the psammomatous type is
      exceptionally rare, and only six such cases have been reported in the literature;
      the current patient represents the seventh case.

PMID- 21948574
TI  - Brunner's gland hyperplasia: an unusual cause of gastrointestinal bleeding.
AB  - A case of Brunner's gland hyperplasia presenting as gastrointestinal bleeding is
      reported herein. A 40-year-old male presented to our hospital with features of
      upper gastrointestinal bleeding. The patient had a history of passing black tarry
      stools for the last two days. Upper gastrointestinal endoscopy was done, which
      showed a pedunculated polypoid lesion in the second part of the duodenum with
      active bleeding at the base of the polyp. Adrenaline was injected around the
      bleeding site; however, the patient continued to bleed. He was taken for surgery.
      A laparotomy was done, and the duodenum was mobilized and opened. A large
      pedunculated polyp measuring approximately 2 cm was found with bleeding at the
      base. Polypectomy was done. Histopathological examination of the specimen showed
      mature Brunner's gland with normal duodenal mucosa at the surface. Diagnosis of
      Brunner's gland hyperplasia was made. The patient is under follow-up and is
      symptom-free.

PMID- 21948575
TI  - Severe jaundice due to coexistence of Dubin-Johnson syndrome and hereditary
      spherocytosis: a case report.
AB  - Dubin-Johnson syndrome is a chronic, benign, intermittent jaundice, mostly of
      conjugated hyperbilirubinemia. The level of bilirubin is not expected to be more
      than 20 mg/dl in this syndrome. In this article, we report a patient who was
      evaluated for hyperbilirubinemia and liver function test abnormalities and
      diagnosed with Dubin-Johnson syndrome coexisting with hereditary spherocytosis.
      We suggest that other diseases should be investigated if patients with Dubin
      Johnson syndrome present with severe hyperbilirubinemia. Dubin-Johnson syndrome
      accompanied by hemolytic diseases might also have high coproporphyrin levels (as
      in Rotor's syndrome) than expected in pure Dubin-Johnson syndrome.

PMID- 21948576
TI  - Ectopic pancreas presenting with intractable diarrhea: case report.
AB  - Ectopic pancreas is an uncommon congenital anomaly, which is usually found
      incidentally in clinical practice. It presents with nonspecific gastrointestinal
      symptoms like epigastric pain and dyspepsia and rarely with the clinical findings
      of obstructive jaundice or intestinal obstruction, or it may mimic
      gastrointestinal system cancer. Herein, we describe a case of ectopic pancreas in
      the duodenum, which was the cause of the intractable diarrhea. In our patient,
      upper gastrointestinal endoscopy and endoscopic ultrasonography revealed a 1.5 cm
      submucosal lesion, which was umbilicated centrally with a normal in appearance
      overlying mucosa. Endoscopic biopsy of the lesion was normal. Pathological
      examination of the lesion after surgical excision was compatible with ectopic
      pancreas. After total excision of the lesion, the clinical findings of the
      patient normalized. Ectopic pancreas presenting with diarrhea has not been
      reported previously in the literature.

PMID- 21948577
TI  - Hydatid cyst of the pancreas: a case report and brief review.
AB  - A 45-year-old male farmer had noticed a swelling of the left side of his
      hypochondrium that persisted for six months. He had no history of severe
      abdominal pain, jaundice, fever, or weight loss. On evaluation, the patient was
      found to have hydatid cyst of the pancreas. He was managed surgically. In this
      case report, we emphasize the preoperative diagnosis in hydatid cyst of the
      pancreas.

PMID- 21948578
TI  - Acute pancreatitis: an initial presentation of systemic lupus erythematosus.
AB  - Acute pancreatitis is a rare, but fatal, manifestation of systemic lupus
      erythematosus. Only 10 systemic lupus erythematosus-associated pancreatitis cases
      were found in a search of published articles. We report a 24-year-old woman
      without significant medical history, who was admitted with abdominal pain, nausea
      and vomiting, which was diagnosed as pancreatitis. It was discovered to be the
      initial presentation of systemic lupus erythematosus. The first time she was
      admitted, she recovered with conservative management and steroid therapy. Two
      months later, she was readmitted to our hospital with symptoms and signs of acute
      abdomen, which was attributed to her discontinuation of the therapeutic regimen
      with corticosteroids just after her previous discharge. She underwent laparotomy
      twice for signs of peritonitis. Despite administration of a monoclonal antibody,
      rituximab, she died due to the progression of systemic lupus erythematosus
      activity.

PMID- 21948579
TI  - Unusual tumor: primary gastric choriocarcinoma.

PMID- 21948580
TI  - Endoscopic removal of an ingested toothpick from the prepyloric antrum in an
      adult woman.

PMID- 21948581
TI  - Small bowel obstruction: a presenting symptom of squamous cell carcinoma of the
      lung.

PMID- 21948582
TI  - Very rare coincidence: perforated duodenal ulcer and olive seed phytobezoar.

PMID- 21948583
TI  - Iatrogenic pneumoscrotum after colonoscopy.

PMID- 21948584
TI  - Cefixime-induced hepatotoxicity.

PMID- 21948585
TI  - A technique for solution of alpha loop-formed guidewire in the bile duct.

PMID- 21948586
TI  - Unusual retrograde movement of an open safety pin: the second case in the
      literature.

PMID- 21948587
TI  - Does the evidence support the use of mild hypothermia after cardiac arrest? Yes.

PMID- 21948588
TI  - Speed of updating online evidence based point of care summaries: prospective
      cohort analysis.
AB  - OBJECTIVE: To evaluate the ability of international point of care information
      summaries to update evidence relevant to medical practice. DESIGN: Prospective
      cohort bibliometric analysis. SETTING: Top five point of care information
      summaries (Clinical Evidence, EBMGuidelines, eMedicine, Dynamed, UpToDate) ranked
      for coverage of medical conditions, editorial quality, and evidence based
      methodology. MAIN OUTCOME MEASURES: From June 2009 to May 2010 we measured the
      incidence of research findings relating to potentially eligible newsworthy
      evidence. As samples, we chose systematic reviews rated as relevant by
      international research networks (such as, Evidence-Based Medicine, ACP Journal
      Club, and the Cochrane Collaboration). Every month we assessed whether each
      sampled review was cited in at least one chapter of the five summaries. The
      cumulative updating rate was analysed with Kaplan-Meier curves. Results From
      April to December 2009, 128 reviews were retrieved; 53% (68) from the literature
      surveillance journals and 47% (60) from the Cochrane Library. At nine months,
      Dynamed had cited 87% of the sampled reviews, while the other summaries had cited
      less than 50%. The updating speed of Dynamed clearly led the others. For
      instance, the hazard ratios for citations in EBM Guidelines and Clinical Evidence
      versus the top performer were 0.22 (95% confidence interval 0.17 to 0.29) and
      0.03 (0.01 to 0.05). Conclusions Point of care information summaries include
      evidence relevant to practice at different speeds. A qualitative analysis of
      updating mechanisms is needed to determine whether greater speed corresponds to
      more appropriate incorporation of new information.

PMID- 21948589
TI  - Does the evidence support the use of mild hypothermia after cardiac arrest? No.

PMID- 21948590
TI  - A patient with rectal discharge and fever.

PMID- 21948591
TI  - Make defeating cancer a "national priority" says US progress report.

PMID- 21948592
TI  - Welsh health minister plans to make the NHS more accountable.

PMID- 21948593
TI  - Expanding the action of duplex RNAs into the nucleus: redirecting alternative
      splicing.
AB  - Double-stranded RNAs are powerful agents for silencing gene expression in the
      cytoplasm of mammalian cells. The potential for duplex RNAs to control expression
      in the nucleus has received less attention. Here, we investigate the ability of
      small RNAs to redirect splicing. We identify RNAs targeting an aberrant splice
      site that restore splicing and production of functional protein. RNAs can target
      sequences within exons or introns and affect the inclusion of exons within SMN2
      and dystrophin, genes responsible for spinal muscular atrophy and Duchenne
      muscular dystrophy, respectively. Duplex RNAs recruit argonaute 2 (AGO2) to pre
      mRNA transcripts and altered splicing requires AGO2 expression. AGO2 promotes
      transcript cleavage in the cytoplasm, but recruitment of AGO2 to pre-mRNAs does
      not reduce transcript levels, exposing a difference between cytoplasmic and
      nuclear pathways. Involvement of AGO2 in splicing, a classical nuclear process,
      reinforces the conclusion from studies of RNA-mediated transcriptional silencing
      that RNAi pathways can be adapted to function in the mammalian nucleus. These
      data provide a new strategy for controlling splicing and expand the reach of
      small RNAs within the nucleus of mammalian cells.

PMID- 21948594
TI  - ChEMBL: a large-scale bioactivity database for drug discovery.
AB  - ChEMBL is an Open Data database containing binding, functional and ADMET
      information for a large number of drug-like bioactive compounds. These data are
      manually abstracted from the primary published literature on a regular basis,
      then further curated and standardized to maximize their quality and utility
      across a wide range of chemical biology and drug-discovery research problems.
      Currently, the database contains 5.4 million bioactivity measurements for more
      than 1 million compounds and 5200 protein targets. Access is available through a
      web-based interface, data downloads and web services at:
      https://www.ebi.ac.uk/chembldb.

PMID- 21948595
TI  - Knowledge transfer and translation: examining how teratogen information is
      disseminated.
AB  - BACKGROUND: Well-executed knowledge transfer and translation (KT) has become a
      vital part of effective health management. Following the thalidomide disaster,
      women and their health care providers became fearful of medications and
      environmental exposures that could affect the health of the unborn child.
      Therefore, it is important to disseminate evidenced-based information to pregnant
      women and their health care providers, enabling them to make empowered decisions
      regarding exposures during pregnancy. OBJECTIVES: The objectives were twofold:
      (1) to explore the knowledge transfer process of teratology information from the
      research community to health care providers, pregnant women, and the general
      public; and (2) to examine how this impacts pregnant women and their health care
      providers who require this information. METHODS: We searched the peer reviewed
      literature (PUBMED, MEDLINE, and EMBASE), retrieved and examined original studies
      and review articles, and identified relevant data to evaluate how KT is conducted
      in this field. RESULTS: We found that KT and teratology information is very
      complex, with confusing information, over-estimated fears of teratogenicity, as
      well as unhelpful, often negatively biased information from the media. Of all the
      methods we identified, Teratogen Information Services (TIS) appears to conduct
      the most effective KT approaches in this field. CONCLUSION: It is evident that KT
      in this area needs improvement. Women and their health care providers are highly
      impacted by the type of teratology information they receive, affecting for
      example, deciding to terminate a wanted pregnancy or discontinue a needed
      pharmacotherapy. When disseminating information in this very sensitive and
      complex field, it is imperative that good KT strategies are used, encompassing
      the availability and appropriate interpretation of information. It is most
      important that an evidence-based decision is made to ensure the optimal outcome
      for both the mother and her unborn child.

PMID- 21948596
TI  - Bone marrow fat quantification of osteoporotic vertebral compression fractures:
      comparison of multi-voxel proton MR spectroscopy and chemical-shift gradient-echo
      MR imaging.
AB  - BACKGROUND: Only a few studies have used in/opposed phase method for a
      quantitative evaluation of fat fraction in the spine. PURPOSE: To compare
      multivoxel proton MR spectroscopy and chemical-shift gradient-echo MR imaging for
      bone marrow fat quantification in vertebral compression fractures (VCF). MATERIAL
      AND METHODS: Vertebral marrow fat quantification in fifteen patients was measured
      at 3.0-T. Multi-voxel proton spectroscopy (MRS) and in/opposed-phase MR imaging
      using a fat map build with a triple-echo gradient-echo sequence was used. All the
      patients had benign vertebral collapse. Bone marrow fat content was evaluated by
      both techniques in compressed (acute or chronic) and in non-compressed vertebrae.
      RESULTS: The percentage of fat fraction measured by the triple-echo sequence was
      well correlated with those calculated by MRS (r(2) = 0.85; P < 10(-4)). There was
      a significant decrease of fat fraction in acute VCF versus both chronic VCF (P <
      10(-9)) and non-fractured vertebrae (P < 10(-7)). There was no significant
      difference in fat fraction evaluated by both techniques between non-fractured
      vertebrae and chronic VCF. CONCLUSION: We have validated the in/opposed phase
      method compared with MRS for vertebral bone marrow fat quantification. The fat
      mapping using a triple-echo gradient-echo sequence allows distinguishing acute
      and chronic benign VCF.

PMID- 21948598
TI  - Role of physical activity in new onset fractures after percutaneous
      vertebroplasty.
AB  - BACKGROUND: Increased mobility and physical activity after successful vertebral
      augmentation procedure might increase the risk of new-onset fractures. PURPOSE:
      To determine whether new-onset fracture following vertebroplasty is associated
      with specific type of physical activity. MATERIAL AND METHODS: A total of 107
      patients underwent at least two procedures of percutaneous vertebroplasty. Among
      them, 30 patients who sustained a post-vertebroplasty fracture(s), were
      stratified by fracture-causing activity and examined the incidence of the initial
      and post-vertebroplasty fractures, time to post-vertebroplasty fractures,
      duration of anti-osteoporotic therapy, T-score, and body mass index. RESULTS: The
      following percentages correspond to patients with fractures sustained pre- and
      post-vertebroplasty, respectively; spontaneous fractures in 17% and 7% (P =
      0.20), sitting in 7% and 3% (P = 0.50), walking or standing in 7% and 20% (P =
      0.10), housework in 3% and 3% (P > 0.99), coughing or sneezing in 0% and 20% (P =
      0.003), exercise in 7% and 17% (P = 0.20), lifting in 10% and 17% (P = 0.40) and
      falling in 50% and 13% (P = 0.002). Different levels of activity were not
      significantly associated with time to incidence of post-vertebroplasty fractures.
      Anti-osteoporotic medications were administered to 33% of patients before
      vertebroplasty and 37% after the vertebroplasty (P = 0.78); medications were
      administered to these groups for 16 and 25 months, respectively (P = 0.39).
      CONCLUSION: A significantly elevated risk of new onset fracture with increased
      physical activity was not identified. However, patients should be carefully
      counseled after vertebroplasty to optimize medical therapy for osteoporosis and
      also to use extreme care when engaging in even moderate physical activity.

PMID- 21948597
TI  - PET imaging in a longitudinal non-Hodgkin's lymphoma study: association with
      tumor volume.
AB  - BACKGROUND: Computed tomography (CT) is generally used in the evaluation of the
      treatment response of non-Hodgkin's lymphoma (NHL) patients. Instead of
      morphological images, positron emission tomography (PET) shows metabolic
      information that is connected to tumor activity, cell proliferation rate, and,
      thus, prognosis. PURPOSE: To determine the prognostic value of PET for tumor
      volume reduction measured by CT and magnetic resonance imaging (MRI) along with
      clinical characteristics in NHL patients. MATERIAL AND METHODS: We imaged 21 B
      cell type NHL patients using whole-body 18F-FDG-PET at the onset and the
      completion of treatment and at six-month follow-up. The maximum standardized
      uptake value (SUV(max)) was calculated. Morphological tumor volume calculations
      were assessed using both MRI and CT. Additionally, patients underwent thorough
      clinical examination including several laboratory tests. RESULTS: A high SUV(max)
      was able to predict significant tumor volume reduction at the beginning of
      treatment, but the relation to pure tumor volume was poor. CONCLUSION: The
      SUV(max) values derived from FDG-PET seemed to correlate with volume changes but
      not with their absolute values or laboratory tests. Unlike MRI and CT, FDG-PET
      showed the disappearance of active tumors after treatment.

PMID- 21948599
TI  - Practice-related improvements in postural control during rapid arm movement in
      older adults: a preliminary study.
AB  - BACKGROUND: Postural control associated with self-paced movement is critical for
      balance in older adults. The present study aimed to investigate the effects of a
      virtual reality-based program on the postural control associated with rapid arm
      movement in this population. METHODS: From an upright standing position,
      participants performed rapid arm-raising movements toward a target. Practice
      related changes were assessed by pre- and posttest comparisons of hand kinematics
      and center of pressure displacement parameters measured in a training group (mean
      age: 71.50 +/- 2.67 years, n = 8) and a control group (mean age: 72.87 +/- 3.09
      years, n = 8). Training group participants took part in six sessions (35-40
      minutes per session, three sessions per week). During the two test sessions, arm
      raising was analyzed under two conditions of stimuli: choice reaction time and
      simple reaction time. RESULTS: We observed improvements in the arm movement after
      training under both conditions of stimuli. The initial phase of the center of
      pressure displacement, especially the anticipatory postural adjustments, was
      improved in the choice reaction time condition. CONCLUSIONS: Our short training
      program resulted in motor optimization of the postural control associated with
      rapid arm movements, and this implies central changes in motor programming.

PMID- 21948600
TI  - Transcriptome mining of active biosynthetic pathways and their associated
      products in Streptomyces flaveolus.

PMID- 21948602
TI  - [Is an intensive glycaemic control beneficial in diabetes type 2?].

PMID- 21948601
TI  - Interplay between non-photochemical plastoquinone reduction and re-oxidation in
      pre-illuminated Chlamydomonas reinhardtii: a chlorophyll fluorescence study.
AB  - In photosynthetic eukaryotes, the redox state of the plastoquinone (PQ) pool is
      an important sensor for mechanisms that regulate the photosynthetic electron
      transport. In higher plants, a multimeric nicotinamide adenine dinucleotide
      (phosphate) (NAD(P))H dehydrogenase (NDH) complex and a plastid terminal oxidase
      (PTOX) are involved in PQ redox homeostasis in the dark. We recently demonstrated
      that in the microalgae Chlamydomonas reinhardtii, which lacks the multimeric NDH
      complex of higher plants, non-photochemical PQ reduction is mediated by a
      monomeric type-II NDH (Nda2). In this study, we further explore the nature and
      the importance of non-photochemical PQ reduction and oxidation in relation to
      redox homeostasis in this alga by recording the 'dark' chlorophyll fluorescence
      transients of pre-illuminated algal samples. From the observation that this
      fluorescence transient is modified by addition of propyl gallate, a known
      inhibitor of PTOX, and in a Nda2-deficient strain we conclude that it reflects
      post-illumination changes in the redox state of PQ resulting from simultaneous
      PTOX and Nda2 activity. We show that the post-illumination fluorescence transient
      can be used to monitor changes in the relative rates of the non-photochemical PQ
      reduction and reoxidation in response to different physiological situations. We
      study this fluorescence transient in algae acclimated to high light and in a
      mutant deficient in mitochondrial respiration. Some of our observations indicate
      that the chlororespiratory pathway participates in redox homeostasis in C.
      reinhardtii.

PMID- 21948603
TI  - [Early treatment of statins after acute coronary syndrome?].

PMID- 21948604
TI  - Effects of nutrient supply, plasma metabolites, and nutritional status of sows
      during transition on performance in the next lactation.
AB  - The aim of the present study was to evaluate the effects of nutrient supply,
      plasma metabolites, and nutritional status of sows during the transition from
      gestation to lactation on performance of piglets during the colostral period and
      throughout lactation. Forty second-parity sows were fed 1 of 4 gestation diets
      containing a different quantity of dietary fiber (171 to 404 g/kg of DM) from
      mating until d 108 of gestation. From d 108 of gestation until weaning (d 28 of
      lactation), sows were fed 1 of 5 lactation diets with a different quantity of
      dietary fat [3 or 8% with different proportions of medium- (MCFA) and long-chain
      fatty acids (LCFA)]. Blood was obtained by jugular venipuncture on d 108 and 112
      of gestation and on d 1 of lactation, and concentrations of plasma glucose, NEFA,
      lactate, acetate, propionate, butyrate, and fatty acids were analyzed. Piglet
      growth and mortality were noted throughout lactation. Piglet mortality during the
      colostral period (0 to 24 h) was affected by the lactation diets and was
      positively related to sow backfat (d 108) and plasma lactate (d 112) and
      negatively related to mean piglet birth weight (P < 0.05). Mean piglet live BW
      gain (LWG) was recorded in the periods 0 to 24 h, 7 to 10 d, 14 to 17 d, and 17
      to 28 d relative to parturition as indirect measures of colostrum yield (0 to 24
      h), milk yield in early lactation (d 7 to 10), and at peak lactation (d 14 to 17
      and d 17 to 28). Effects of gestation and lactation diets on studied sow traits
      were tested on selected days during the transition period and the next lactation,
      and tested statistically on separate days. The LWG in the colostral period was
      positively correlated with mean piglet birth weight (P < 0.001), plasma
      concentrations of propionate and MCFA (P < 0.05), and plasma acetate and butyrate
      (P < 0.1) on d 1 of lactation. The LWG in early lactation was inversely
      correlated with plasma lactate on d 108 (P < 0.05), plasma glucose on d 112, and
      backfat thickness on d 108 (P < 0.10). The LWG at peak lactation was positively
      correlated with MCFA intake of the sow on d 113 to 115 and backfat thickness on d
      108 during the transition, and negatively correlated with intake of LCFA and ME
      intake on d 108 to 112 (P < 0.05). In conclusion, feeding and body condition of
      sows during the transition from gestation to lactation is important for neonatal
      piglet survival, lactation performance of sows, and piglet growth during the next
      lactation.

PMID- 21948605
TI  - Influence of inducing luteal regression before a modified fixed-time artificial
      insemination protocol in postpartum beef cows on pregnancy success.
AB  - Most fixed-time insemination protocols utilize an injection of GnRH at the
      beginning of the protocol to initiate a new follicular wave. However, the ability
      of GnRH to initiate a new follicular wave is dependent on the stage of the
      estrous cycle. We hypothesized that administering PGF(2alpha) 3 d before
      initiating a fixed-time AI protocol would improve synchrony of follicular waves
      and result in greater pregnancy success. Therefore, our objective was to
      determine whether inducing luteal regression 3 d before a fixed-time AI protocol
      would improve control of follicular turnover and pregnancy success to fixed-time
      AI. Multiparous crossbred cows at 3 locations (n = 108, 296, and 97) were
      randomly assigned to 1 of 2 treatments: 1) PGF(2alpha) [25 mg; intramuscularly
      (i.m.)] on d -9, GnRH (100 MUg; i.m.) and insertion of a controlled internal drug
      releasing device (CIDR) on d -6, PGF(2alpha) (25 mg; i.m.) and CIDR removal with
      PGF(2alpha) (25 mg; i.m.) at CIDR removal on d 0 (PG-CIDR) or 2) GnRH (100 MUg;
      i.m.) and insertion of a CIDR on d -5 and CIDR removal with PGF(2alpha) (25 mg;
      i.m.) at CIDR removal and 4 to 6 h after CIDR removal (5-d CIDR). Cows were time
      inseminated between 66 and 72 h (PG-CIDR) or 70 to 74 h (5-d CIDR) after CIDR
      removal, and GnRH was administered at the time of fixed-time AI. At location 1,
      ovulatory response to the first injection of GnRH was determined by
      ultrasonography at the time of GnRH and 48 h after GnRH administration. Among
      cows with follicles >=10 mm in diameter, more (P = 0.03) PG-CIDR-treated cows
      ovulated after the initial GnRH injection (88%, 43/49) compared with the 5-d CIDR
      treated cows (68%, 34/50). Pregnancy outcome was not influenced by location (P =
      0.96), age of the animal (P = 1.0), cycling status (P = 0.99), BCS (P = 1.0), or
      any 2-way interactions (P >= 0.13). However, pregnancy success was influenced by
      synchronization protocol (P = 0.04). Pregnancy outcome was greater (P = 0.04) for
      the PG-CIDR protocol (64%) compared with the 5-d CIDR protocol (55%). In summary,
      control of follicular turnover was improved by inducing luteal regression 3 d
      before initiation of a fixed-time AI protocol, and pregnancy success was improved
      with the PG-CIDR protocol compared with the 5-d protocol.

PMID- 21948606
TI  - Effect of dietary phytic acid on performance and nutrient uptake in the small
      intestine of piglets.
AB  - An experiment was conducted with piglets to determine the effect of dietary
      phytic acid supplementation on performance, electrophysiological properties of
      jejunum mounted in Ussing chambers, sodium-dependent glucose transporter 1
      (SGLT1) protein expression in jejunum, and plasma glucose and Na concentrations.
      Sixteen piglets with an average initial BW of 7.40 +/- 0.36 kg were randomly
      assigned to 2 experimental diets with 8 piglets per diet. The diets were casein
      cornstarch-based and were either unsupplemented or supplemented with 2% phytic
      acid (as Na phytate). The basal diet was formulated to meet the recommendation of
      NRC (1998) for energy, AA, minerals, and vitamins for piglets. The experiment
      lasted for 21 d, and at the end, BW gain and feed consumption were determined,
      and blood samples were collected for determination of plasma glucose and Na
      concentrations. The piglets were then euthanized to determine jejunal
      electrophysiological properties (transmural potential difference and short
      circuit current) and SGLT1 protein expression. Phytic acid supplementation
      reduced ADG (P = 0.002), ADFI (P = 0.017), and G:F (P = 0.001) from 316.1 to
      198.2 g, 437.4 to 360.3 g, and 0.721 to 0.539 g/g, respectively. Phytic acid
      supplementation also tended to reduce (P = 0.088) potential difference (-3.80 vs.
      -2.23 mV) and reduced (P = 0.023) short-circuit current from 8.07 to 0.1
      MUA/cm(2). However, phytic acid supplementation did not affect SGLT1 protein, and
      blood plasma glucose and Na concentrations. In conclusion, dietary phytic acid
      reduced growth performance and transmural short-circuit current in the jejunum of
      piglets. The reduced transmural short-circuit current in the jejunum by phytic
      acid implies reduced active Na transport in the jejunum by the phytic acid.
      Therefore, it seems that dietary phytic acid reduces growth performance of pigs
      partly through reduced capacity of the small intestine to absorb Na.

PMID- 21948607
TI  - Sow and litter response to supplemental dietary fat in lactation diets during
      high ambient temperatures.
AB  - The objective of this experiment was to determine the impact of supplemental
      dietary fat on total lactation energy intake and sow and litter performance
      during high ambient temperatures (27 +/- 3 degrees C). Data were collected from
      337 mixed-parity sows from July to September in a 2,600-sow commercial unit in
      Oklahoma. Diets were corn-soybean meal-based with 7.5% corn distillers dried
      grains with solubles and 6.0% wheat middlings and contained 3.24 g of
      standardized ileal digestible Lys/Mcal of ME. Animal-vegetable fat blend (A-V)
      was supplemented at 0, 2, 4, or 6%. Sows were balanced by parity, with 113, 109,
      and 115 sows representing parity 1, 2, and 3 to 7 (P3+), respectively. Feed
      disappearance (subset of 190 sows; 4.08, 4.18, 4.44, and 4.34 kg/d, for 0, 2, 4,
      and 6%, respectively; P < 0.05) and apparent caloric intake (12.83, 13.54, 14.78,
      and 14.89 Mcal of ME/d, respectively; P < 0.001) increased linearly with
      increasing dietary fat. Gain:feed (sow and litter BW gain relative to feed
      intake) was not affected (P = 0.56), but gain:Mcal ME declined linearly with the
      addition of A-V (0.16, 0.15, 0.15, and 0.14 for 0, 2, 4, and 6%, respectively; P
      < 0.01). Parity 1 sows (3.95 kg/d) had less (P < 0.05) feed disappearance than P2
      (4.48 kg/d) and P3+ (4.34 kg/d) sows. Body weight change in P1 sows was greater
      (P < 0.01) than either P2 or P3+ sows (-0.32 vs. -0.07 and 0.12 kg/d), whereas
      backfat loss was less (P < 0.05) and loin depth gain was greater (P < 0.05) in
      P3+ sows compared with P1 and P2 sows. Dietary A-V improved litter ADG (P < 0.05;
      1.95, 2.13, 2.07, and 2.31 kg/d for 0, 2, 4, and 6% fat, respectively) only in
      P3+ sows. Sows bred within 8 d after weaning (58.3, 72.0, 70.2, and 74.7% for 0,
      2, 4, and 6%, respectively); conception rate (78.5, 89.5, 89.2, and 85.7%) and
      farrowing rate (71.4, 81.4, 85.5, and 78.6%) were improved (P < 0.01) by
      additional A-V, but weaning-to-breeding interval was not affected. Rectal and
      skin temperature and respiration rate of sows were greater (P < 0.002) when
      measured at wk 3 compared with wk 1 of lactation, but were not affected by A-V
      addition. Parity 3+ sows had lower (P < 0.05) rectal temperature than P1 and P2
      sows, and respiration rate was reduced (P < 0.001) in P1 sows compared with P2
      and P3+ sows. In conclusion, A-V improved feed disappearance and caloric intake,
      resulting in improved litter weight gain and subsequent reproductive performance
      of sows; however, feed and caloric efficiency were negatively affected.

PMID- 21948608
TI  - Microsatellite mapping of quantitative trait loci affecting female reproductive
      tract characteristics in Meishan x Large White F(2) pigs.
AB  - A QTL analysis of female reproductive data from a 3-generation experimental cross
      between Meishan and Large White pig breeds is presented. Six F(1) boars and 23
      F(1) sows, progeny of 6 Large White boars and 6 Meishan sows, produced 502 F(2)
      gilts whose reproductive tract was collected after slaughter at 30 d of
      gestation. Five traits [i.e., the total weight of the reproductive tract, of the
      empty uterine horns, of the ovaries (WOV), and of the embryos], as well as the
      length of uterine horns (LUH), were measured and analyzed with and without
      adjustment for litter size. Animals were genotyped for a total of 137 markers
      covering the entire porcine genome. Analyses were carried out based on interval
      mapping methods, using a line-cross regression and a half-full sib maximum
      likelihood test. A total of 18 genome-wide significant (P < 0.05) QTL were
      detected on 9 different chromosomes (i.e., SSC 1, 5, 6, 7, 9, 12, 13, 18, and X).
      Five genome-wide significant QTL were detected for LUH, 4 for weight of the empty
      uterine horns and WOV, 2 for total weight of the reproductive tract, and 1 for
      weight of the embryos. Twenty-two additional suggestive QTL were also detected.
      The largest effects were obtained for LUH and WOV on SSC13 (9.2 and 7.0% of trait
      phenotypic variance, respectively). Meishan alleles had both positive (e.g., on
      SSC7) and negative effects (e.g., on SSC13) on the traits investigated. Moreover,
      the QTL were generally not fixed in founder breeds, and opposite effects were in
      some cases obtained in different families. Although reproductive tract
      characteristics had only a moderate correlation with reproductive performances,
      most of the major QTL detected in this study were previously reported as
      affecting female reproduction, generally with reduced significance levels. This
      study thus shows that focusing on traits with high heritability might help to
      detect loci involved in low heritability major traits for breeding.

PMID- 21948609
TI  - Consumer assessment of beef strip loin steaks of varying fat levels.
AB  - A consumer study was conducted in Lubbock, Texas, to determine the effects of fat
      level of beef strip steaks on the palatability traits of tenderness, juiciness,
      flavor liking, and overall liking, while further investigating the window of
      acceptability for fat content of beef. Thirty beef strip loins were selected by
      trained personnel to equally represent USDA Prime, High Choice (upper 1/3
      Choice), Low Choice (lower 1/3 Choice), Select, and Standard. Proximate analysis
      was conducted on all strip loins to determine percentage fat, moisture, protein,
      and collagen. Three strip loins from each quality grade were selected based on
      fat percentages from proximate analysis to best represent each USDA quality grade
      for use in the consumer evaluations. Strip loins were fabricated into 2.5-cm
      steaks, and further processed into 5 * 5 cm pieces. In addition to the US-sourced
      product, beef LM pieces from 6 Australian Wagyu steers (Wagyu) and 6 Australian
      grain finished steers (Australian) were used in the consumer evaluations.
      Consumers (n = 120) were served 7 samples: a warm-up sample, 1 sample from each
      USDA quality grade treatment, and either a Wagyu or Australian sample, in a
      balanced order in accordance with a 6 * 6 Latin square. Consumers rated each
      steak sample for tenderness, juiciness, flavor, and overall liking and rated each
      palatability trait as either acceptable or unacceptable. Moreover, consumers
      rated each sample as unsatisfactory, good everyday quality, better than everyday
      quality, or premium quality. Tenderness, juiciness, flavor liking, and overall
      liking increased with increasing fat content (P < 0.05). However, Wagyu and
      Australian samples did not follow this trend for flavor and overall liking. A
      decrease in consumer acceptability of each palatability trait was observed as fat
      level decreased (P < 0.05). Consumer overall liking was correlated (P < 0.05)
      with consumer tenderness (r = 0.76) and juiciness ratings (r = 0.73), but most
      highly correlated with flavor liking (r = 0.88). Results of this study indicated
      that increased fat level in beef strip steaks positively affected tenderness,
      juiciness, flavor liking, and overall liking of beef strip steaks. Moreover,
      flavor liking was the most highly correlated palatability trait with overall
      liking. In US-sourced samples, fat level had a large effect on the flavor liking
      of beef as determined by consumers.

PMID- 21948610
TI  - Genetic analysis of beef fatty acid composition predicted by near-infrared
      spectroscopy.
AB  - The aims of this study were 1) to investigate the potential application of near
      infrared spectroscopy (NIRS) to predict intramuscular fat (IMF) and fatty acid
      (FA) composition of individual meat samples, 2) to estimate heritability of IMF
      and FA NIRS-based predictions, and 3) to assess the statistical relevance of the
      genetic background of such predictions by using the Bayes factor (BF) procedure.
      Young Piemontese bulls (n = 1,298) were raised and fattened on 124 farms, and
      slaughtered at the same commercial abattoir. Intramuscular fat content and FA
      composition were analyzed on a random subset of 148 samples of minced and
      homogenized longissimus thoracis muscle. Near-infrared spectroscopy spectra were
      collected on all samples (n = 1,298) in reflectance mode between 1,100 and 2,498
      nm (every 2 nm) using fresh minced meat samples. Calibration models developed
      from the random subset of 148 samples were used to predict IMF and FA contents of
      the remaining 1,150 samples. Intramuscular fat content and FA predictions were
      analyzed under a Bayesian univariate animal linear models, and the statistical
      relevance of heritability estimates was assessed through BF; the model with
      polygenic additive effects was favored when BF > 1. In general, satisfactory
      results (R(2) > 0.60) were obtained for 6 out of the 8 major FA (C14:0, C:16:0,
      C16:1, C18:0, C18:1n-9 cis/trans, and C18:1n-11 trans), 6 out of the 19 minor FA
      (C10:0, C12:0, C17:0, C17:1, C18:2 cis-9,trans-11, and C20:2), and the total SFA,
      MUFA, and PUFA. Bayes factors between models with and without a genetic component
      provided values greater than 1 for IMF, C14:0, C16:0, C18:1n-9 cis/trans, C17:0,
      C17:1, C20:2, SFA, MUFA, and PUFA. The greatest BF was reached by C20:2 (BF >10),
      suggesting strong evidence of genetic determinism, whereas IMF, C18:1n-9
      cis/trans, C17:0, C17:1, MUFA, and PUFA showed substantial evidence favoring the
      numerator model (3.16 < BF < 10). Point estimates of heritabilities for FA
      predicted by NIRS were low to moderate (0.07 to 0.21). Results support that NIRS
      is a useful technique to satisfactorily predict some FA of meat. The existence of
      an important genetic determinism affecting FA profile has been confirmed,
      suggesting that FA composition of meat can be genetically modified.

PMID- 21948611
TI  - Effect of maternal seaweed extract supplementation on suckling piglet growth,
      humoral immunity, selected microflora, and immune response after an ex vivo
      lipopolysaccharide challenge.
AB  - The present study was conducted to investigate the effect of maternal dietary
      supplementation (n = 10 sows/treatment) with seaweed extract (SWE: 0 vs. 10.0
      g/d) from d 107 of gestation until weaning (d 26) on neonatal piglet growth,
      humoral immunity, intestinal morphology, selected intestinal microflora, and VFA
      concentrations. Furthermore, this study examined the effect of dietary treatment
      on the immune response after an ex vivo Escherichia coli lipopolysaccharide (LPS)
      tissue challenge at weaning in a 2 * 2 factorial arrangement. The main factors
      consisted of sow dietary treatment (SWE or control) and immunological challenge
      (yes or no). The SWE supplement (10.0 g/d) contained laminarin (1.0 g), fucoidan
      (0.8 g), and ash (8.2 g) and was extracted from a Laminaria spp. The SWE
      supplemented sows had greater colostrum IgA (P < 0.01) and had a trend for
      greater IgG (P = 0.062) concentrations compared with non-SWE-supplemented sows.
      Piglets suckling SWE-supplemented sows had greater serum IgG (P < 0.05)
      concentrations on d 14 of lactation compared with those suckling non-SWE
      supplemented sows. Dietary SWE supplementation decreased fecal Enterobacteriaceae
      populations in sows at parturition (P < 0.05), and piglets suckling SWE
      supplemented sows had a decreased colonic E. coli population at weaning (P <
      0.01) compared with non-SWE-supplemented sows. Lipopolysaccharide challenge
      increased the mRNA abundances of the pro-inflammatory cytokines IL-1alpha and IL
      6 (P < 0.01) in ileal tissue and tumor necrosis factor (TNF)-alpha in colonic (P
      < 0.01) tissue. There was a treatment * LPS challenge interaction for ileal TNF
      alpha mRNA expression (P < 0.05). Piglets suckling SWE-supplemented sows had
      greater TNF-alpha mRNA expression after ex vivo LPS challenge compared with non
      SWE-supplemented sows (P < 0.05). However, there was no effect of sow dietary
      treatment on TNF-alpha mRNA expression in the unchallenged ileal tissue. Piglet
      BW at birth and weaning, and small intestinal morphology were unaffected by sow
      dietary treatment under current experimental conditions. In summary, these
      results demonstrate an important immunomodulatory role of SWE supplementation
      characterized by enhanced colostral IgA and IgG concentrations, greater piglet
      circulatory IgG concentrations on d 14 of lactation, and enhanced TNF-alpha mRNA
      expression in the ileum after an ex vivo LPS challenge. These results indicate
      that SWE supplementation enhanced piglet immune function and colonic microflora
      at weaning.

PMID- 21948612
TI  - Effects of organic selenium supplementation on growth performance, carcass
      measurements, tissue selenium concentrations, characteristics of reproductive
      organs, and testis gene expression profiles in boars.
AB  - The objective was to compare growth and physiological responses in boars fed
      diets supplemented with organic or inorganic sources of Se. At weaning, crossbred
      boars (n = 117; 8.3 kg of BW) were placed in nursery pens (3 boars/pen) and
      assigned within BW blocks to receive on an ad libitum basis 1 of 3 dietary
      treatments: I) basal diets with no supplemental Se (controls), II) basal diets
      supplemented with 0.3 mg/kg of organic Se, and, III) basal diets supplemented
      with 0.3 mg/kg of sodium selenite (13 pens/dietary treatment). Average daily gain
      (470 g/d), ADFI (896 g/d), and G:F (0.54) were similar among groups. Blood Se
      concentrations were greater (P < 0.01) for boars consuming organic Se (107.5 +/-
      4.8 ug/L) or sodium selenite (114.7 +/- 4.8 ug/L) compared with controls (28.4 +/
      4.8 ug/L). Intact pens of boars (11 pens/dietary treatment) were moved to a grow
      finish barn and continued to receive appropriate diets on an ad libitum basis.
      Average daily gain (1,045 g/d) and ADFI (2,716 g/d) were similar among groups.
      Gain:feed was affected by treatment (P = 0.02) and was greater (P < 0.06) for
      boars fed organic Se (0.378 +/- 0.004) compared with boars fed sodium selenite
      (0.368 +/- 0.004) or controls (0.363 +/- 0.004). Blood Se concentrations were
      greater (P < 0.01) in grow-finish boars consuming organic Se (198.9 +/- 5.5 ug/L)
      than boars consuming sodium selenite (171.4 +/- 5.4 ug/L) or controls (26.7 +/-
      5.4 ug/L). Treatment did not affect (P > 0.15) HCW, dressing percent, carcass
      length, LM area, standardized fat-free lean, lean percentage, backfat thickness,
      visual color, firmness, marbling, or Minolta loin color scores. Selenium
      supplementation did not affect (P > 0.17) testis or accessory sex gland sizes.
      Concentrations of Se in loin, liver, kidney, testis, cauda epididymis, and
      accessory sex glands were greatest (P < 0.01) in boars receiving organic Se,
      intermediate in boars receiving sodum selenite, and least in control boars.
      Microarray analysis of testis gene expression did not detect differences (P >
      0.05) due to dietary treatment. Testis gene expression of glutathione peroxidase
      4, as determined using quantitative PCR, was increased (P < 0.01) in boars fed
      organic Se compared with those fed sodium selenite. In summary, dietary
      supplementation of boars with organic Se failed to alter ADG or ADFI but enhanced
      G:F during grow-finish. More research is needed to discern the mechanism by which
      organic Se improves feed efficiency in boars.

PMID- 21948613
TI  - Concise review: The magic act of generating induced pluripotent stem cells: many
      rabbits in the hat.
AB  - Since the seminal discovery by Yamanaka et al. demonstrating that four
      transcription factors were capable of inducing nuclear reprogramming to a
      pluripotent state, a plethora of publications have followed aimed at improving
      the efficiency, simplicity, and safety of the original methodology that was based
      on the use of integrating retroviruses. A better understanding of the basic
      mechanisms behind reprogramming as well as an improvement in tissue culture
      conditions have allowed for the development of new tools based on different
      molecular approaches, such as excisable and nonintegrating vectors, RNA,
      proteins, and small compounds, among others. In most instances, a dynamic
      interplay exists between each method's efficiency of reprogramming versus overall
      safety, and these points need to be considered when choosing a particular
      approach. Regardless, the fast pace at which this field has advanced in recent
      years attracted many investigators to enter into the induced pluripotent stem
      cell (iPSC) world and has made the process of nuclear reprogramming and iPSC
      generation a routine lab technique.

PMID- 21948614
TI  - Protein modulation in mouse heart under acute and chronic hypoxia.
AB  - Exploring cellular mechanisms underlying beneficial and detrimental responses to
      hypoxia represents the object of the present study. Signaling molecules
      controlling adaptation to hypoxia (HIF-1alpha), energy balance (AMPK),
      mitochondrial biogenesis (PGC-1alpha), autophagic/apoptotic processes regulation
      and proteomic dysregulation were assessed. Responses to acute hypoxia (AH) and
      chronic hypoxia (CH) in mouse heart proteome were detected by 2-D DIGE, mass
      spectrometry and antigen-antibody reactions. Both in AH and CH, the results
      indicated a deregulation of proteins related to sarcomere stabilization and
      muscle contraction. Neither in AH nor in CH the HIF-1alpha stabilization was
      observed. In AH, the metabolic adaptation to lack of oxygen was controlled by
      AMPK activation and sustained by an up-regulation of adenosylhomocysteinase and
      acetyl-CoA synthetase. AH was characterized by the mitophagic protein Bnip 3
      increment. PGC-1alpha, a master regulator of mitochondrial biogenesis, was down
      regulated. CH was characterized by the up-regulation of enzymes involved in
      antioxidant defense, in aldehyde bio-product detoxification and in misfolded
      protein degradation. In addition, a general down-regulation of enzymes
      controlling anaerobic metabolism was observed. After 10 days of hypoxia,
      cardioprotective molecules were substantially decreased whereas pro-apoptotic
      molecules increased accompained by down-regulation of specific target proteins.

PMID- 21948615
TI  - NTP-CERHR expert panel report on the developmental toxicity of soy infant
      formula.
AB  - Soy infant formula contains soy protein isolates and is fed to infants as a
      supplement to or replacement for human milk or cow milk. Soy protein isolates
      contains estrogenic isoflavones (phytoestrogens) that occur naturally in some
      legumes, especially soybeans. Phytoestrogens are nonsteroidal, estrogenic
      compounds. In plants, nearly all phytoestrogens are bound to sugar molecules and
      these phytoestrogen-sugar complexes are not generally considered hormonally
      active. Phytoestrogens are found in many food products in addition to soy infant
      formula, especially soy-based foods such as tofu, soy milk, and in some over-the
      counter dietary supplements. Soy infant formula was selected for National
      Toxicology Program (NTP) evaluation because of (1) the availability of large
      number of developmental toxicity studies in laboratory animals exposed to the
      isoflavones found in soy infant formula (namely, genistein) or other soy
      products, as well as few studies on human infants fed soy infant formula, (2) the
      availability of information on exposures in infants fed soy infant formula, and
      (3) public concern for effects on infant or child development. On October 2, 2008
      (73 FR 57360), the NTP Center for the Evaluation of Risks to Human Reproduction
      (CERHR) announced its intention to conduct an updated review of soy infant
      formula to complete a previous evaluation that was initiated in 2005. Both the
      current and previous evaluations relied on expert panels to assist the NTP in
      developing its conclusions on the potential developmental effects associated with
      the use of soy infant formula, presented in the NTP Brief on Soy Infant Formula.
      The initial expert panel met on March 15 to 17, 2006, to reach conclusions on the
      potential developmental and reproductive toxicities of soy infant formula and its
      predominant isoflavone constituent genistein. The expert panel reports were
      released for public comment on May 5, 2006 (71 FR 28368). On November 8, 2006 (71
      FR 65537), CERHR staff released draft NTP Briefs on Genistein and Soy Formula
      that provided the NTP's interpretation of the potential for genistein and soy
      infant formula to cause adverse reproductive and/or developmental effects in
      exposed humans. However, CERHR did not complete these evaluations, finalize the
      briefs, or issue NTP Monographs on these substances based on this initial
      evaluation. Between 2006 and 2009, a substantial number of new publications
      related to human exposure or reproductive and/or developmental toxicity were
      published for these substances. Thus, CERHR determined that updated evaluations
      of genistein and soy infant formula were needed. However, the current evaluation
      focuses only on soy infant formula and the potential developmental toxicity of
      its major isoflavone components, e.g. genistein, daidzein (and estrogenic
      metabolite, equol), and glycitein. This updated evaluation does not include an
      assessment on the potential reproductive toxicity of genistein following
      exposures during adulthood as was carried out in the 2006 evaluation. CERHR
      narrowed the scope of the evaluation because the assessment of reproductive
      effects of genistein following exposure to adults was not considered relevant to
      the consideration of soy infant formula use in infants during the 2006
      evaluation. To obtain updated information about soy infant formula for the CERHR
      evaluation, the PubMed (Medline) database was searched from February 2006 to
      August 2009 with genistein/genistin, daidzein/daidzin, glycitein/glycitin, equol,
      soy, and other relevant keywords. References were also identified from the
      bibliographies of published literature. The updated expert panel report
      represents the efforts of a 14-member panel of government and nongovernment
      scientists, and was prepared with assistance from NTP staff. The finalized
      report, released on January 15, 2010 (75 FR 2545), reflects consideration of
      public comments received on a draft report that was released on October 19, 2009,
      for public comment and discussions that occurred at a public meeting of the
      expert panel held December 16 to 18, 2009 (74 FR 53509). The finalized report
      presents conclusions on (1) the strength of scientific evidence that soy infant
      formula or its isoflavone constituents are developmental toxicants based on data
      from in vitro, animal, or human studies; (2) the extent of exposures in infants
      fed soy infant formula; (3) the assessment of the scientific evidence that
      adverse developmental health effects may be associated with such exposures; and
      (4) knowledge gaps that will help establish research and testing priorities to
      reduce uncertainties and increase confidence in future evaluations. The Expert
      Panel expressed minimal concern for adverse developmental effects in infants fed
      soy infant formula. This level of concern represents a "2" on the five-level
      scale of concern used by the NTP that ranges from negligible concern ("1") to
      serious concern ("5"). The Expert Panel Report on Soy Infant Formula was
      considered extensively by NTP staff in preparing the 2010 NTP Brief on Soy Infant
      Formula, which represents the NTP's opinion on the potential for exposure to soy
      infant formula to cause adverse developmental effects in humans. The NTP
      concurred with the expert panel that there is minimal concern for adverse effects
      on development in infants who consume soy infant formula. This conclusion was
      based on information about soy infant formula provided in the expert panel
      report, public comments received during the course of the expert panel
      evaluation, additional scientific information made available since the expert
      panel meeting, and peer reviewer critiques of the draft NTP Brief by the NTP
      Board of Scientific Counselors (BSC) on May 10, 2010 (Meeting materials are
      available at http://ntp.niehs.nih.gov/go/9741.). The BSC voted in favor of the
      minimal concern conclusion with 7 yes votes, 3 no votes, and 0 abstentions. One
      member thought that the conclusion should be negligible concern and two members
      thought that the level of concern should be higher than minimal concern. The
      NTP's response to the May 10, 2010 review ("peer-review report") is available on
      the NTP website at http://ntp.niehs.nih.gov/go/9741. The monograph includes the
      NTP Brief on Soy Infant Formula as well as the entire final Expert Panel Report
      on Soy Infant Formula. Public comments received as part of the NTP's evaluation
      of soy infant formula and other background materials are available at
      http://cerhr.niehs.nih.gov/evals/index.html.

PMID- 21948616
TI  - Enantioselective enzymatic desymmetrization of prochiral allenic diols.

PMID- 21948617
TI  - [Raltegravir in a special case: patient with HIV and Burkitt's lymphoma].
AB  - HISTORY AND CLINICAL FINDINGS: A 38-year-old HIV positive man suffered from right
      upper abdominal pain and oesophageal reflux syndromes. He was in a good general
      state of health and nutrition with no concomitant symptoms. INVESTIGATIONS: A
      small bowel tumor and slight soor esophagitis had been diagnosed by esophago
      gastroduodenoscopy. The tumor was histologically classified as Burkitt?s
      lymphoma. TREATMENT AND OUTCOME: The patient received 6 cycles of chemotherapy
      according to the B-ALL protocol, and antiretroviral therapy with lamivudine (300
      mg), abacavir (600 mg) und raltegravir (2 * 400 mg) was initiated immediately.
      After the first cycle of chemotherapy a complete remission of Burkitt?s lymphoma
      was achieved. Laboratory parameters recovered after completion of 6 cycles to a
      value of 400 CD4-positive lymphocytes/mm (3) with a viral load of HIV-1-RNA 20 -
      300 copies/ml in plasma. CONCLUSION: Immediate initiation of antiretroviral
      therapy is essential after the diagnosis of AIDS-defining symptoms. The choice of
      an appropriate treatment regimen is a critical factor in order to avoid toxic
      drug interactions and adverse events while maintaining a highly effective
      treatment.

PMID- 21948618
TI  - Isolation and purification of the major photosynthetic antenna, fucoxanthin-Chl
      a/c protein, from cultured discoid germilings of the brown Alga, Cladosiphon
      okamuranus TOKIDA (Okinawa Mozuku).
AB  - A chlorophyll c binding membrane intrinsic light-harvesting complex, the
      fucoxanthin-chlorophyll a/c protein (FCP), was isolated from cultured discoid
      germilings of an edible Japanese brown alga, Cladosiphon (C.) okamuranus TOKIDA
      (Okinawa Mozuku in Japanese). The discoid germiling is an ideal source of brown
      algal photosynthetic pigment-protein complexes in terms of its size and easiness
      of cultivation on a large scale. Ion-exchange chromatography was crucial for the
      purification of FCP from solubilized thylakoid proteins. The molecular weight of
      the purified FCP assembly was estimated to be ~56 kDa using blue native-PAGE.
      Further subunit analyses using 2D-PAGE revealed that the FCP assembled as a
      trimer consisting of two distinguishable subunits having molecular weights of
      18.2 (H) and 17.5 (L) kDa. Fluorescence and fluorescence-excitation spectra
      confirmed that the purified FCP assembly was functionally intact.

PMID- 21948619
TI  - Combination of retinal pigment epithelium cell-conditioned medium and
      photoreceptor outer segments stimulate mesenchymal stem cell differentiation
      toward a functional retinal pigment epithelium cell phenotype.
AB  - Recent studies have suggested that bone marrow-derived mesenchymal stem cells
      (BMMSCs) are capable of retinal tissue-specific differentiation but not retinal
      pigment epithelium (RPE) cell-specific differentiation. Photoreceptor outer
      segments (POS) contribute to RPE development and maturation. However, there has
      been no standard culture system that fosters the differentiation of BMMSCs into
      mature RPE cells in vitro. In this study, we investigated if the soluble factors
      from RPE cells and POS could differentiate BMMSCs into cells having a phenotype
      characteristic of RPE cells. Rat BMMSCs were separately co-cultured with RPE
      cells, or they were exposed to either control medium, RPE cell-conditioned medium
      (RPECM), POS, or a combination of RPECM and POS (RPECM-POS). After 7 days, the
      cells were analyzed for morphology and the expression of RPE markers (cytokeratin
      8, CRALBP, and RPE65) to assess the RPE differentiation. Significantly higher
      pigment accumulation and increased protein expression of the three markers were
      seen in cells cultured in RPECM-POS than in other treated cultures. Furthermore,
      the RPECM-POS-treated cultures displayed ultrastructural features typical of RPE
      cells, expressed RPE cell functional proteins, and had the capability to
      phagocytose POS. Together, theses results suggest the combination of RPECM and
      POS stimulate BMMSCs differentiation toward a functional RPE phenotype. Our
      results provide the foundation for a new route to RPE regenerative therapy
      involving BMMSCs. Future work isolating the active agent in RPECM and POS would
      be useful in therapies for RPE diseases or in developing appropriately pre
      differentiated BMMSCs for tissue-engineered RPE reconstruction.

PMID- 21948620
TI  - Limbal epithelial stem/progenitor cells attract stromal niche cells by SDF
      1/CXCR4 signaling to prevent differentiation.
AB  - Corneal epithelial stem cells (SCs) are an ideal model for investigating how
      adult lineage-committed epithelial SCs are regulated by an anatomically defined
      and accessible niche, that is, limbal palisades of Vogt, located between the
      cornea and the conjunctiva. We have used collagenase digestion to isolate the
      entire limbal epithelial SCs and subjacent mesenchymal cells, and we have
      demonstrated that their close association is crucial for promoting epithelial
      clonal growth, implying that the latter serves as niche cells (NCs). After their
      close association was disrupted by trypsin/EDTA, single SCs and NCs could reunite
      to generate sphere growth in three-dimensional Matrigel in the embryonic SC
      medium, and that such sphere growth initiated by SC-NC reunion was mediated by
      SDF-1 uniquely expressed by limbal epithelial progenitor cells and its receptor
      CXCR4, but not CXCR7, strongly expressed by limbal stromal NCs. Inhibition of
      CXCR4 by AMD3100 or a blocking antibody to CXCR4 but not CXCR7 disrupted their
      reunion and yielded separate spheres with a reduced size, while resultant
      epithelial spheres exhibited more corneal differentiation and a notable loss of
      holoclones. For the first time, these results provide strong evidence supporting
      that limbal SC function depends on close physical association with their native
      NCs via SDF-1/CXCR4 signaling. This novel in vitro model of sphere growth with
      NCs can be used for investigating how limbal SC self-renewal and fate decision
      might be regulated in the limbal niche.

PMID- 21948621
TI  - Targeting pi-conjugated multiple donor-acceptor motifs exemplified by
      tetrathiafulvalene-linked quinoxalines and tetrabenz[bc,ef,hi,uv]ovalenes:
      synthesis, spectroscopic, electrochemical, and theoretical characterization.
AB  - An efficient synthetic approach to a symmetrically functionalized
      tetrathiafulvalene (TTF) derivative with two diamine moieties, 2-[5,6-diamino-4,7
      bis(4-pentylphenoxy)-1,3-benzodithiol-2-ylidene]-4,7-bis(4-pentylphenoxy)-1,3
      benzodithiole-5,6-diamine (2), is reported. The subsequent Schiff-base reactions
      of 2 afford large pi-conjugated multiple donor-acceptor (D-A) arrays, for
      example, the triad 2-[4,9-bis(4-pentylphenoxy)-1,3-dithiolo[4,5-g]quinoxalin-2
      ylidene]-4,9-bis(4-pentylphenoxy)-1,3-dithiolo[4,5-g]quinoxaline (8) and the
      corresponding tetrabenz[bc,ef,hi,uv]ovalene-fused pentad 1, in good yields and
      high purity. The novel redox-active nanographene 1 is so far the largest known
      TTF-functionalized polycyclic aromatic hydrocarbon (PAH) with a well-resolved
      (1)H NMR spectrum. The electrochemically highly amphoteric pentad 1 and triad 8
      exhibit various electronically excited charge-transfer states in different
      oxidation states, thus leading to intense optical intramolecular charge-transfer
      (ICT) absorbances over a wide spectral range. The chemical and electrochemical
      oxidations of 1 result in an unprecedented TTF(?+) radical cation dimerization,
      thereby leading to the formation of [1(?+)](2) at room temperature in solution
      due to the stabilizing effect, which arises from strong pi-pi interactions.
      Moreover, ICT fluorescence is observed with large solvent-dependent Stokes shifts
      and quantum efficiencies of 0.05 for 1 and 0.035 for 8 in dichloromethane.

PMID- 21948622
TI  - Commentary on "incidence and nature of testicular toxicity findings...".

PMID- 21948623
TI  - OsO4.streptavidin: a tunable hybrid catalyst for the enantioselective cis
      dihydroxylation of olefins.

PMID- 21948624
TI  - Component analysis of a school-based substance use prevention program in Spain:
      contributions of problem solving and social skills training content.
AB  - The objective of the present research was to examine the contribution of two
      intervention components, social skills training and problem solving training, to
      alcohol- and drug-related outcomes in a school-based substance use prevention
      program. Participants included 341 Spanish students from age 12 to 15 who
      received the prevention program Saluda in one of four experimental conditions:
      full program, social skills condition, problem solving condition, and a wait-list
      control group. Students completed self-report surveys at the pretest, posttest
      and 12-month follow-up assessments. Compared to the wait-list control group, the
      three intervention conditions produced reductions in alcohol use and intentions
      to use other substances. The intervention effect size for alcohol use was
      greatest in magnitude for the full program with all components. Problem-solving
      skills measured at the follow-up were strongest in the condition that received
      the full program with all components. We discuss the implications of these
      findings, including the advantages and disadvantages of implementing tailored
      interventions to students by selecting intervention components after a skills
      based needs assessment.

PMID- 21948625
TI  - Concise review: Deciphering the mechanism behind induced pluripotent stem cell
      generation.
AB  - Regenerative medicine using spluripotent/multipotent stem cells holds a great
      promise in developing therapies for treating developmental abnormalities,
      degenerative disorders, and aging-related illness. However, supply and safety of
      the stem cells are two major problems with today's regenerative medicine. Recent
      development of induced pluripotent stem cells (iPSCs) has overcome the supply
      shortages by allowing the reprogramming of patients' body cells to embryonic stem
      cell (ESC)-like pluripotent cells. Still, the potential tumorigenicity of iPSCs
      remains as an obstacle. During early embryogenesis ESCs can be generated without
      tumor formation; therefore, understanding the mechanisms underlying ESC
      generation may help us to prevent iPSC tumorigenicity. Previous studies have
      shown that an ESC-enriched noncoding RNA, miR-302, induces somatic cell
      reprogramming (SCR) to form iPSCs, suggesting its pivotal role in stem cell
      generation. Recent research further revealed that miR-302-induced SCR involves an
      epigenetic reprogramming mechanism similar to the natural zygotic reprogramming
      process in the two- to eight-cell-stage embryos. These findings indicate that miR
      302, as a cytoplasmic gene silencer, inhibits the translation of multiple key
      epigenetic regulators, including AOF1/2, methyl-CpG binding proteins 1 and 2, and
      DNA (cytosine-5-)-methyltransferase 1, to induce global DNA demethylation, which
      subsequently triggers the activation of the previously defined factors Oct4,
      Sox2, and Nanog to complete the reprogramming process. The same mechanism was
      also found in the event of somatic cell nuclear transfer. Based on these advanced
      understandings, this review describes the currently established SCR mechanism--as
      compared to the natural process of early ESC formation--and demonstrates how stem
      cell researchers may use this mechanism to improve iPSC generation.

PMID- 21948626
TI  - Identification of soybean purple acid phosphatase genes and their expression
      responses to phosphorus availability and symbiosis.
AB  - BACKGROUND AND AIMS: Purple acid phosphatases (PAPs) are members of the metallo
      phosphoesterase family and have been known to play important roles in phosphorus
      (P) acquisition and recycling in plants. Low P availability is a major constraint
      to growth and production of soybean, Glycine max. Comparative studies on
      structure, transcription regulation and responses to phosphate (Pi) deprivation
      of the soybean PAP gene family should facilitate further insights into the
      potential physiological roles of GmPAPs. METHODS: BLAST searches were performed
      to identify soybean PAP genes at the phytozome website. Bioinformatic analyses
      were carried out to investigate their gene structure, conserve motifs and
      phylogenetic relationships. Hydroponics and sand-culture experiments were carried
      out to obtain the plant materials. Quantitative real-time PCR was employed to
      analyse the expression patterns of PAP genes in response to P deficiency and
      symbiosis. KEY RESULTS: In total, 35 PAP genes were identified from soybean
      genomes, which can be classified into three distinct groups including six
      subgroups in the phylogenetic tree. The expression pattern analysis showed
      flowers possessed the largest number of tissue-specific GmPAP genes under normal
      P conditions. The expression of 23 GmPAPs was induced or enhanced by Pi
      starvation in different tissues. Among them, nine GmPAP genes were highly
      expressed in the Pi-deprived nodules, whereas only two GmPAP genes showed
      significantly increased expression in the arbuscular mycorrhizal roots under low
      P conditions. CONCLUSIONS: Most GmPAP genes are probably involved in P
      acquisition and recycling in plants. Also we provide the first evidence that some
      members of the GmPAP gene family are possibly involved in the response of plants
      to symbiosis with rhizobia or arbuscular mycorrhizal fungi under P-limited
      conditions.

PMID- 21948628
TI  - Charity challenges government's plans to scrap legal aid for negligence claims.

PMID- 21948627
TI  - Is leaf dry matter content a better predictor of soil fertility than specific
      leaf area?
AB  - BACKGROUND AND AIMS: Specific leaf area (SLA), a key element of the 'worldwide
      leaf economics spectrum', is the preferred 'soft' plant trait for assessing soil
      fertility. SLA is a function of leaf dry matter content (LDMC) and leaf thickness
      (LT). The first, LDMC, defines leaf construction costs and can be used instead of
      SLA. However, LT identifies shade at its lowest extreme and succulence at its
      highest, and is not related to soil fertility. Why then is SLA more frequently
      used as a predictor of soil fertility than LDMC? METHODS: SLA, LDMC and LT were
      measured and leaf density (LD) estimated for almost 2000 species, and the
      capacity of LD to predict LDMC was examined, as was the relative contribution of
      LDMC and LT to the expression of SLA. Subsequently, the relationships between
      SLA, LDMC and LT with respect to soil fertility and shade were described. KEY
      RESULTS: Although LD is strongly related to LDMC, and LDMC and LT each contribute
      equally to the expression of SLA, the exact relationships differ between
      ecological groupings. LDMC predicts leaf nitrogen content and soil fertility but,
      because LT primarily varies with light intensity, SLA increases in response to
      both increased shade and increased fertility. CONCLUSIONS: Gradients of soil
      fertility are frequently also gradients of biomass accumulation with reduced
      irradiance lower in the canopy. Therefore, SLA, which includes both fertility and
      shade components, may often discriminate better between communities or treatments
      than LDMC. However, LDMC should always be the preferred trait for assessing
      gradients of soil fertility uncoupled from shade. Nevertheless, because leaves
      multitask, individual leaf traits do not necessarily exhibit exact functional
      equivalence between species. In consequence, rather than using a single stand
      alone predictor, multivariate analyses using several leaf traits is recommended.

PMID- 21948629
TI  - Risks from forced detoxification from heroin are being ignored, conference hears.

PMID- 21948630
TI  - Understanding the fast pyrolysis of lignin.
AB  - In the present study, pyrolysis of corn stover lignin was investigated by using a
      micro-pyrolyzer coupled with a GC-MS/FID (FID=flame ionization detector). The
      system has pyrolysis-vapor residence times of 15-20 ms, thus providing a regime
      of minimal secondary reactions. The primary pyrolysis product distribution
      obtained from lignin is reported. Over 84 % mass balance and almost complete
      closure on carbon balance is achieved. In another set of experiments, the
      pyrolysis vapors emerging from the micro-pyrolyzer are condensed to obtain lignin
      derived bio-oil. The chemical composition of the bio-oil is analyzed by using GC
      MS and gel permeation chromatography techniques. The comparison between results
      of two sets of experiments indicates that monomeric compounds are the primary
      pyrolysis products of lignin, which recombine after primary pyrolysis to produce
      oligomeric compounds. Further, the effect of minerals (NaCl, KCl, MgCl(2), and
      CaCl(2)) and temperature on the primary pyrolysis product distribution is
      investigated. The study provides insights into the fundamental mechanisms of
      lignin pyrolysis and a basis for developing more descriptive models of biomass
      pyrolysis.

PMID- 21948631
TI  - Asymmetric reduction of ketones by phosphoric acid derived catalysts.

PMID- 21948632
TI  - Cupuassu (Theobroma grandiflorum) peel as potential source of dietary fiber and
      phytochemicals in whole-bread preparations.
AB  - Cupuassu (Theobroma grandiflorum) is a fruit tree native to the Brazilian Amazon.
      Cupuassu beans are extensively used in the Brazilian food industry. Fat from
      cupuassu beans, which are a rich source of triacylglycerols and fatty acids, is
      used extensively in the production of candies and confectionery in the northern
      and northeastern regions of Brazil. The potential use of the agro-industrial by
      products of cupuassu has only slightly been addressed by the scientific
      community. Often, such by-products are sources of bioactive compounds with
      functional properties. Thus, the aims of this study were to characterize the use
      of cupuassu peel flour (CPF) and to examine the potential of CPF as a partial
      replacement in the preparation of breads through various means: chemical
      analyses, determination of protein digestibility, tannins, phytic acid and
      phenolic contents, pH, color, volume, and acceptance tests. The results show that
      CPF is a potential source of dietary fiber (79.81%), mainly insoluble fiber
      (78.29%), and breads made with added CPF present high dietary fiber content (5.40
      and 6.15 g/100 g for inclusions with 6 and 9% CPF, respectively) and
      phytochemical values. The use of this by-product did not produce substantial
      changes in the physical, chemical or rheological characteristics of breads.
      Therefore, breads enhanced with CPF may be a convenient functional food, offering
      a good source of dietary fiber and phytochemicals. Breads prepared with 6% added
      CPF presented an acceptable overall quality to consumers.

PMID- 21948634
TI  - Recombinant immunosuppressive protein from Pimpla hypochondrica venom (rVPr1)
      increases the susceptibility of Mamestra brassicae larvae to the fungal
      biological control agent, Beauveria bassiana.
AB  - Although fungi are used to control a variety of insect pests, it is accepted that
      their usage could be increased if their efficacy was greater. The outcome of the
      interaction of a fungus and a pest insect may be influenced by a number of
      criteria, including the ability of the insect to mount effective immune responses
      against the pathogen. In view of this, we aimed to determine if a recombinant
      immunosuppressive wasp venom protein (rVPr1) can increase the susceptibility of
      larvae of the lepidopteran pest, Mamestra brassicae, to the fungal biological
      control agent, Beauveria bassiana. Bioassays indicated that when larvae were
      injected with 3.5 ul of rVPr1 and 100 B. bassiana conidia (combined injection
      assays), a significant reduction in survival of larvae occurred compared with
      each treatment on its own (P=0.006). Similar results were obtained when larvae
      were dipped in a solution containing 3 * 10(6) B. bassiana conidia per ml and
      then injected with 3.5 ul of rVPr1 2 days later (topical application assays),
      (P<0.001). These results indicate that rVPr1 can increase the efficacy of B.
      bassiana toward a lepidopteran pest, and are discussed within the context of
      insect immune responses and integrated pest management.

PMID- 21948633
TI  - Effects of feeding potato pulp on cholesterol metabolism and its association with
      cecal conditions in rats.
AB  - To clarify the functional properties of potato pulp (PP), a waste product
      resulting from extraction of starch from potatoes, we examined the effects of PP
      on cholesterol metabolism and cecal conditions in rats. Plasma total cholesterol
      (T-Chol) levels were lower in rats fed a PP-supplemented diet for four weeks than
      in those fed a control diet. Cecal pH was lowered due to an increase in the
      levels of cecal total short-chain fatty acids, especially butyrate, in the PP
      group compared to the control group. Furthermore, animals fed with the PP
      supplemented diet showed increased cecal ratios of Lactobacillus and Clostridia
      and decreased cecal ratios of Bacteroides and Gammaproteobacteria with slightly
      negative and positive correlations with plasma T-Chol levels, respectively. In
      conclusion, ingestion of PP for four weeks is likely to improve both cecal
      conditions and cholesterol metabolism, suggesting that PP has prebiotic effects.

PMID- 21948635
TI  - Communication disorders related to cleft palate, craniofacial anomalies, and
      velopharyngeal dysfunction.

PMID- 21948636
TI  - Anatomy and physiology of the velopharyngeal mechanism.
AB  - Understanding the normal anatomy and physiology of the velopharyngeal mechanism
      is the first step in providing appropriate diagnosis and treatment for children
      born with cleft lip and palate. The velopharyngeal mechanism consists of a
      muscular valve that extends from the posterior surface of the hard palate (roof
      of mouth) to the posterior pharyngeal wall and includes the velum (soft palate),
      lateral pharyngeal walls (sides of the throat), and the posterior pharyngeal wall
      (back wall of the throat). The function of the velopharyngeal mechanism is to
      create a tight seal between the velum and pharyngeal walls to separate the oral
      and nasal cavities for various purposes, including speech. Velopharyngeal closure
      is accomplished through the contraction of several velopharyngeal muscles
      including the levator veli palatini, musculus uvulae, superior pharyngeal
      constrictor, palatopharyngeus, palatoglossus, and salpingopharyngeus. The tensor
      veli palatini is thought to be responsible for eustachian tube function.

PMID- 21948637
TI  - Types of clefts and multianomaly craniofacial conditions.
AB  - Speech-language pathologists (SLPs) in the public schools or other nonmedical
      settings rarely see infants or small children with unrepaired clefts. When
      children with repaired clefts appear in their caseloads, it may be difficult to
      comprehend what the situation was before the child had surgery. Clefts vary
      widely in their original severity, which has a direct bearing on how the repaired
      cleft looks and how the orofacial structures (lip, teeth, and palate) affect
      speech when the child comes into the SLP's caseload. It is important to
      understand that a high percentage of children with nonsyndromic clefts also have
      other structural or functional disorders that affect their ability to accomplish
      their goals in life. Multianomaly, complex craniofacial conditions (associations,
      sequences, and syndromes) are even rarer in nonmedically based SLP practices.
      However, because medical habilitation for these cases is now much more easily
      available and because families who frequent the Internet will know that the
      services of an SLP may be needed for their child, it is necessary for the SLP to
      know some basic characteristics of these conditions and to know where to find
      needed information.

PMID- 21948638
TI  - Feeding issues and interventions in infants and children with clefts and
      craniofacial syndromes.
AB  - Problems with oral feeding occur in varying degrees in infants born with cleft
      lip/palate and/or craniofacial syndromes. The extent of clefting is associated
      with the severity of feeding problems, and if cleft lip/palate occurs in
      conjunction with a craniofacial syndrome, additional structural, airway, and
      neuromotor issues may be present. The infant's feeding and swallowing skills may
      be significantly impaired, characterized by inefficient oral feeding skills
      coupled with poor airway protection ability during swallowing. Inadequate airway
      protection during swallowing has serious implications for the infant's
      respiratory health as sequelae of chronic aspiration during feeding may include
      recurrent respiratory illness, pneumonia, and lung damage. Feeding difficulty in
      nonsyndromic and syndromic cleft lip/palate infants has been documented as source
      of considerable stress for parents and can have a potential negative effect on
      the parent-infant bonding process. Therefore, timely identification of feeding
      problems by the speech pathologist with subsequent intervention and modification
      in the feeding method is essential, along with provision of early feeding
      instruction to families. The objective of this article is to review expert
      opinion and available evidence regarding factors that influence feeding success
      and efficiency in infants with nonsyndromic and syndromic cleft lip/palate. The
      types of compensatory strategies or interventions that are effective in
      alleviation of feeding and swallowing difficulties will be described. Descriptive
      reports, expert opinion, and available evidence from clinical trials to support
      the use of feeding interventions in treatment are reviewed.

PMID- 21948639
TI  - Cognitive and language issues associated with cleft lip and palate.
AB  - Language and cognitive performance of children with cleft palate with/without
      cleft lip (CP +/- L) have received relatively little attention in the literature
      to date. The lack of attention directed toward these areas is probably attributed
      to two factors. First, the speech characteristics associated with velopharyngeal
      inadequacy are undoubtedly the most salient problems encountered by clinicians
      treating these children and thus have taken priority in research for many years.
      Second, early findings suggesting little difference between these children and
      their typically developing peers in language and cognition simply discouraged
      additional study. More recent investigations, however, have expanded the scope of
      study to include toddlers and adults and utilized alternative methodologies to
      study this population. In this article, we will summarize the literature and
      explore recent findings associated with language and cognition in children with
      CP +/- L. In addition, we will also examine performance of children with
      velocardiofacial syndrome-a common syndrome associated with CP +/- L.

PMID- 21948640
TI  - Disorders of resonance and airflow secondary to cleft palate and/or
      velopharyngeal dysfunction.
AB  - The purpose of this article is to help the reader understand what contributes to
      normal resonance for speech production. In addition, the reader will learn about
      the types of resonance disorders and their characteristics. The causes of
      resonance disorders will be described with a guideline on how they should be
      treated. This article also includes a discussion of normal airflow for speech and
      the perceptual speech characteristics that often occur when there is abnormal
      nasal airflow. Secondary characteristics of nasal airflow, including weak or
      omitted consonants, short utterance length, nasal grimace, and compensatory
      articulation productions, are also described.

PMID- 21948641
TI  - Types and causes of velopharyngeal dysfunction.
AB  - The velopharyngeal valve is responsible for production of oral speech sounds.
      There are three components to normal velopharyngeal function: anatomy,
      physiology, and learning. velopharyngeal dysfunction (VPD) is a condition where
      the velopharyngeal valve does not close consistently and completely during the
      production of oral sounds. Velopharyngeal dysfunction can be caused by abnormal
      anatomy (velopharyngeal insufficiency), abnormal neurophysiology (velopharyngeal
      incompetence), or particular articulation errors (velopharyngeal mislearning).
      The purpose of this article is to acquaint the reader with what is required for
      normal velopharyngeal function. In addition, there will be a discussion of the
      types of velopharyngeal dysfunction and various causes of each. Implications for
      treatment and prognosis will be discussed.

PMID- 21948642
TI  - Perceptual assessment of resonance and velopharyngeal function.
AB  - Cleft lip is an anomaly that primarily affects aesthetics, whereas cleft palate
      is an anomaly that primarily affects function, particularly speech. In fact, the
      main reason for repairing the palate is to provide adequate structure and
      function for normal speech production. Despite undergoing palatoplasty surgery,
      20 to 30% of children with repaired cleft palate will demonstrate some degree of
      velopharyngeal dysfunction, resulting in abnormal speech. Velopharyngeal
      dysfunction is also seen in individuals without a history of cleft palate for
      various reasons. Because the symptoms of velopharyngeal dysfunction have a
      variety of causes, a comprehensive evaluation is very important to make the
      appropriate recommendations for treatment. The purpose of this article is to
      discuss the clinical assessment of velopharyngeal function for speech, using low
      tech and "no-tech" procedures.

PMID- 21948643
TI  - Instrumental assessment of velopharyngeal closure for speech.
AB  - The presence of a palatal cleft at birth should not prevent good speech
      production in most children provided they have (1) appropriate surgical
      intervention to close the palate at or around the child's first birthday, (2)
      careful monitoring of speech development throughout childhood, (3) speech therapy
      when needed, and (4) secondary surgical or speech-prosthetic intervention when
      needed. When managed carefully by an experienced, well-prepared multidisciplinary
      team that applies the criteria listed above, ~70% of children with nonsyndromic
      palatal clefts will have no significant difficulties with speech intelligibility
      or speech quality due to velopharyngeal insufficiency by the time they enter
      elementary school. Speech assessment is the first step toward comprehensive team
      management of children with cleft palate. The purpose of this chapter is to
      describe the use of instrumentation in the evaluation of speech of children with
      palatal clefts, within the context of a multidisciplinary team. The focus of this
      article is on instruments that are used to supplement the perceptual assessment
      to document current speech status and plan management strategies.

PMID- 21948644
TI  - Speech therapy for errors secondary to cleft palate and velopharyngeal
      dysfunction.
AB  - Individuals with a history of cleft lip/palate or velopharyngeal dysfunction may
      demonstrate any combination of speech sound errors, hypernasality, and nasal
      emission. Speech sound distortion can also occur due to other structural
      anomalies, including malocclusion. Whenever there are structural anomalies,
      speech can be affected by obligatory distortions or compensatory errors.
      Obligatory distortions (including hypernasality due to velopharyngeal
      insufficiency) are caused by abnormal structure and not by abnormal function.
      Therefore, surgery or other forms of physical management are needed for
      correction. In contrast, speech therapy is indicated for compensatory
      articulation productions where articulation placement is changed in response to
      the abnormal structure. Speech therapy is much more effective if it is done after
      normalization of the structure. When speech therapy is appropriate, the
      techniques involve methods to change articulation placement using standard
      articulation therapy principles. Oral-motor exercises, including the use of
      blowing and sucking, are never indicated to improve velopharyngeal function. The
      purpose of this article is to provide information regarding when speech therapy
      is appropriate for individuals with a history of cleft palate or other structural
      anomalies and when physical management is needed. In addition, some specific
      therapy techniques are offered for the elimination of common compensatory
      articulation productions.

PMID- 21948645
TI  - Suboptimal image focus broadens retinal vessel caliber measurement.
AB  - PURPOSE: Studies have used central retinal arteriolar (CRAE) and central retinal
      venular (CRVE) calibers, measured from images produced with computerized image
      analysis, to detect risk factors for systemic diseases. The authors explored
      suboptimal image focus as a possible contributing factor to artificially larger
      vascular caliber measurements. METHODS: From the reading center image
      collections, 30 digital retinal images were selected for optimum quality. Image
      analysis software was used to derive nine progressively blurred versions of the
      originals. IVAN measurement software was used to measure CRAE and CRVE in the
      original and the blurred series derived from them. To check the adequacy of the
      simulation, progressively defocused series of images were taken of several
      volunteers. RESULTS: For CRAE, each level of simulated blurring produced a
      statically significant increase in apparent vessel caliber from the original
      (P<0.01, Wilcoxon signed rank test). For an average CRAE of 160 MUm, mean
      broadening with minimal/moderate/severe blurring was 3 MUm/12 MUm/33 MUm. For
      CRVE, every blurring level beyond the first was found to be significant (P<0.01).
      From an average CRVE of 200 MUm, mean broadening ranged from 0 to 11 MUm with
      minimal to severe blurring. Analysis of the progressively defocused series taken
      of volunteers yielded similar results overall. CONCLUSIONS: Suboptimal focus can
      result in erroneously larger vessel caliber measurements. Slight blurring has a
      minimal effect, but more severe blurring has a progressively greater effect.

PMID- 21948647
TI  - Regulation of lysyl oxidase-like 1 (LOXL1) and elastin-related genes by
      pathogenic factors associated with pseudoexfoliation syndrome.
AB  - PURPOSE: Pseudoexfoliation (PEX) syndrome/glaucoma is a complex, late-onset
      disorder of the elastic fiber system. Strong genetic risk is conferred by the
      lysyl oxidase-like 1 (LOXL1) gene, but additional comodulating factors are
      necessary for the manifestation of the disease. The aim of this study was to
      analyze the effect of various PEX-associated pathogenic factors on the genotype
      correlated expression of LOXL1 and elastin-related genes. METHODS: Cultured human
      Tenon's capsule fibroblasts with high- and low-risk LOXL1 haplotypes were exposed
      to transforming growth factor (TGF)-beta1, interleukin (IL)-6, homocysteine,
      oxidative stress, hypoxia, or ultraviolet (UV) radiation. Changes in the
      expression of LOXL1 and elastic constituents of PEX material and TGF-beta1 were
      assessed by quantitative real-time PCR, Western blotting, immunohistochemistry,
      and electron microscopy. RESULTS: Treatment of fibroblasts with TGF-beta1,
      oxidative stress, UV light, and hypoxia induced a significant increase in
      expression levels of LOXL1 and elastic proteins, whereas the effect of IL-6 was
      limited to induction of elastic constituents. Immunohistochemistry and electron
      microscopy confirmed an upregulation of LOXL1 and elastic fiber proteins and
      their assembly into extracellular microfibrillar networks with focal aggregation
      of microfibrils into PEX-like fibrils on stimulation with TGF-beta1 and oxidative
      stress. Basal and stimulated expression of LOXL1 mRNA and protein was slightly
      decreased in cells carrying the high-risk compared with the low-risk haplotype of
      LOXL1, but the differences between groups were statistically not significant.
      CONCLUSIONS: The findings support the notion that both genetic and nongenetic
      fibrogenic factors, particularly TGF-beta1 and oxidative stress, may cooperate in
      the stable accumulation of PEX aggregates.

PMID- 21948646
TI  - Rasch analysis of the Ocular Surface Disease Index (OSDI).
AB  - PURPOSE: The Ocular Surface Disease Index (OSDI) is a 12-item scale for the
      assessment of symptoms related to dry eye disease and their effect on vision. Its
      reliability and validity have been investigated within the classical test theory
      framework and, more recently, using Rasch analysis. The purpose of the present
      analysis was to more completely investigate the functioning of its response
      category structure, the validity of its three subscales, and the
      unidimensionality of the latent construct it is intended to assess. METHODS:
      Responses to the OSDI from 172 females participating in the Dry Eye in
      Postmenopause (DEiM) study who had previously been diagnosed with dry eye or
      reported significant ocular irritation and dryness were analyzed. Response
      category structure and item fit statistics were evaluated for assessment of model
      fit. Person separation statistics were used to examine the validity of the
      subscales. Unidimensionality was assessed by principal component analysis (PCA)
      of model residuals. RESULTS: The recommended five-category response structure
      resulted in disordered response thresholds. A four-category structure resulted in
      ordered thresholds. Item infit statistics were acceptable for all 12 items.
      Person separation with this category structure was adequate, with a person
      separation index of 2.16. None of the three subscales demonstrated adequate
      person separation. PCA showed one other significant factor onto which the three
      environmental items loaded significantly. CONCLUSIONS: All items demonstrated
      acceptable fit to the model after collapsing categories to order the response
      thresholds. The original subscales did not prove valid, and there is some
      evidence of multidimensionality and poor targeting.

PMID- 21948649
TI  - Concise review: Circulating endothelial progenitor cells for vascular medicine.
AB  - Endothelial progenitor cells (EPCs) have been isolated and shown to be effective
      in animal models of ischemia, and many groups involved in clinical trials have
      demonstrated that EPC therapy is safe and feasible for the treatment of critical
      limb ischemia and cardiovascular diseases. However, many issues in the field of
      EPC biology, especially in regards to the proper and unambiguous molecular
      characterization of these cells still remain unresolved, hampering not only basic
      research but also the effective therapeutic use and widespread application of
      these cells. In this review, we introduce the recent concept of EPC
      identification in terms of hematopoietic and nonhematopoietic EPCs along with the
      development of EPC biology research. Furthermore, we define the role of
      circulating EPCs in postnatal neovascularization to illustrate the future
      direction of EPC therapeutic applications. Next, we review on-going medical
      applications of EPC for cardiovascular and peripheral vascular diseases,
      introduce the practical example of therapeutic application of EPCs to patients
      with ischemic disease, and discuss about the feedback of clinical researches.

PMID- 21948648
TI  - Unique TGFBI protein in lattice corneal dystrophy.
AB  - PURPOSE: Specific components of transforming growth factor-beta-induced protein
      (TGFBIp) responsible for amyloid deposits in lattice corneal dystrophy (LCD) have
      not been delineated. LCD has been associated with various TGFBIp mutations such
      as R124C, L518P, and L527R. Using recombinant TGFBIp, this study was undertaken
      to identify TGFBIp components potentially contributing to the protein deposits in
      LCD. METHODS: Recombinant wild-type (WT) TGFBIp and four mutants (R124C, R124H,
      L518P, and L527R) were generated in HEK293FT cells. WT and mutant TGFBIp were
      collected from crude cell lysates or purified from culture media. Immunoblot
      analyses were performed with four different anti-TGFBIp antibodies raised against
      various regions of TGFBIp. RESULTS: Consistent with the authors' previous
      findings, purified recombinant proteins are more prone to polymerize than crude
      cell lysates. As expected, all monomers and polymers of TGFBIp WT and mutants
      were detected by these antibodies. However, the authors noted WT and TGFBIp
      mutants showed differential reactivities with these antibodies. A 47-kDa band was
      detected in purified 2-tag proteins of L518P by all four antibodies. A unique 43
      kDa band was detected in both 1-tag cell lysates and purified proteins of R124C
      by the authors' custom-made antibody (KE50) and a commercial anti-TGFBIp.
      CONCLUSIONS: Based on its universal reactivity with various antibodies, the
      authors surmise that the 47-kDa protein is a ubiquitous TGFBIp fragment derived
      from the N-terminus of the L518P mutant. The fact that the 43-kDa protein
      fragment was present primarily in R124C and R124H but not in WT implicates its
      potential role in the protein deposits of LCD.

PMID- 21948650
TI  - Time to deterioration in quality of life score as a modality of longitudinal
      analysis in patients with breast cancer.
AB  - PURPOSE: This prospective multicenter study explored different definitions of
      time to deterioration (TTD) in quality of life (QoL) scores, according to
      different cutoffs of the minimal clinically important difference (MCID) as a
      modality for longitudinal QoL assessment in breast cancer patients. METHODS: QoL
      was assessed using the European Organization for Research and Treatment of Cancer
      Quality of Life Questionnaire C30 and BR-23 before surgery, after surgery, and 6
      and 12 months later. The global health score, arm symptoms score (BRAS), and
      breast symptoms score were analyzed. For a given baseline score, QoL was
      considered to have deteriorated if this score decreased by >=5 points at any time
      point after baseline. Analyses were repeated using an MCID of 10 points and
      taking the score after surgery as the reference score (to explore the occurrence
      of response shift). TTD was calculated using the Kaplan-Meier method and Cox
      regression was used to identify independent factors associated with TTD. RESULTS:
      Two hundred thirty-five patients underwent axillary lymph node dissection (ALND),
      222 underwent sentinel lymph node biopsy (SLNB), and 61 underwent SLNB plus ALND.
      Patients who underwent SLNB had a significantly longer TTD for the BRAS dimension
      than those who underwent ALND. Cox multivariate analyses showed that treatment
      using SLNB and age >59 years were independently associated with longer TTD for
      the BRAS, whereas surgery elsewhere than at the Centre Georges Francois Leclerc
      was associated with a shorter TTD. CONCLUSION: Exploration of different
      definitions of TTD in QoL provides meaningful longitudinal QoL results for
      clinicians.

PMID- 21948651
TI  - Discontinuing bevacizumab in patients with glioblastoma: an ethical analysis.
AB  - Glioblastoma (GBM) is a highly lethal malignant brain tumor that expresses
      proangiogenic factors, including vascular endothelial growth factor (VEGF).
      Bevacizumab (Avastin(r); Genentech, Inc., South San Francisco, CA), a monoclonal
      antibody against VEGF, is routinely used in the U.S. to treat GBM patients whose
      tumors have progressed following initial therapy. The Ethics Advisory Committee
      at the Dana-Farber Cancer Institute was asked to provide consultation on two
      cases involving patients with recurrent GBM who were receiving bevacizumab.
      Despite evidence of disease progression, family members advocated for the
      continued use of bevacizumab because of its mild toxicity profile and concern
      that discontinuation would impair quality of life. However, continuing
      bevacizumab in this setting posed physical and financial risks to the patients
      and raised ethical concerns about resource allocation and justice. We analyze the
      ethical questions regarding bevacizumab discontinuation in the setting of
      progressive GBM. We articulate the potential benefits and harms of continuing the
      drug and identify guiding principles for drug discontinuation that should be made
      transparent to patients and families. With the increasing availability of new,
      modestly toxic, expensive drugs for patients with advanced cancer, questions of
      when to stop these drugs will become increasingly relevant.

PMID- 21948652
TI  - Will imatinib compromise reproductive capacity?
AB  - Imatinib mesylate is the first in a family of highly effective, minimally toxic,
      targeted agents used widely to treat Philadelphia-positive leukemias and selected
      other cancers, leading to a steady rise in the prevalence of patients using such
      therapy. Because failure of therapy would require conventional gonadotoxic
      chemotherapeutics, many female patients using imatinib may choose to preserve
      fertility. Herein, we provide evidence of a potential negative effect of imatinib
      on ovarian function by reporting the first case of a woman who showed a severely
      compromised ovarian response to gonadotropin stimulation while on imatinib, with
      a normal ovarian response after stopping this medication.

PMID- 21948653
TI  - DNA microarray analysis identifies CKS2 and LEPR as potential markers of
      meningioma recurrence.
AB  - Meningiomas are the most frequent intracranial tumors. Surgery can be curative,
      but recurrences are possible. We performed gene expression analyses and loss of
      heterozygosity (LOH) studies looking for new markers predicting the recurrence
      risk. We analyzed expression profiles of 23 meningiomas (10 grade I, 10 grade II,
      and 3 grade III) and validated the data using quantitative polymerase chain
      reaction (qPCR). We performed LOH analysis on 40 meningiomas, investigating
      chromosomal regions on 1p, 9p, 10q, 14q, and 22q. We found 233 and 268 probe sets
      to be significantly down- and upregulated, respectively, in grade II or III
      meningiomas. Genes downregulated in high-grade meningiomas were overrepresented
      on chromosomes 1, 6, 9, 10, and 14. Based on functional enrichment analysis, we
      selected LIM domain and actin binding 1 (LIMA1), tissue inhibitor of
      metalloproteinases 3 (TIMP3), cyclin-dependent kinases regulatory subunit 2
      (CKS2), leptin receptor (LEPR), and baculoviral inhibitor of apoptosis repeat
      containing 5 (BIRC5) for validation using qPCR and confirmed their differential
      expression in the two groups of tumors. We calculated DeltaCt values of CKS2 and
      LEPR and found that their differential expression (C-L index) was significantly
      higher in grade I than in grade II or III meningiomas (p < .0001). Interestingly,
      the C-L index of nine grade I meningiomas from patients who relapsed in <5 years
      was significantly lower than in grade I meningiomas from patients who did not
      relapse. These findings indicate that the C-L index may be relevant to define the
      progression risk in meningioma patients, helping guide their clinical management.
      A prospective analysis on a larger number of cases is warranted.

PMID- 21948655
TI  - The oxygen-mediated synthesis of 1,3-butadiynes in continuous flow: using Teflon
      AF-2400 to effect gas/liquid contact.

PMID- 21948656
TI  - Structural characterization, infrared spectroscopy, and theoretical calculations
      for B(C6F5)3-stabilized benzene-ammonia and benzene-water complexes.

PMID- 21948654
TI  - Revisiting the role of antiandrogen strategies in ovarian cancer.
AB  - Androgen receptors are frequently expressed in epithelial ovarian cancer (EOC).
      Their role in the development of EOC is not fully understood. In the present
      review we first discuss the epidemiological data linking a hyperandrogen state to
      a higher risk for ovarian cancer, second describe in vitro studies of the role of
      androgens in influencing the growth of EOC, and finally review the completed
      clinical trials with compounds that exploit the androgen axis in patients with
      ovarian cancer. The therapeutic approaches that inhibit androgen signaling have
      so far produced only modest response rates. In the light of new data regarding
      the role of androgen stimulation in the evolution of EOC and the emergence of new
      compounds used for the treatment of other hormone-driven malignancies, such as
      prostate and breast cancer, we provide suggestions for new studies of
      antiandrogen therapeutics in the treatment of EOC. A specific example is the new
      agent abiraterone. In addition, we propose a panel of molecules that could be
      assessed as potential biomarkers that may aid patient selection for this approach
      in the future.

PMID- 21948662
TI  - Bioinsecticidal activity of Murraya koenigii miraculin-like protein against
      Helicoverpa armigera and Spodoptera litura.
AB  - Miraculin-like proteins, belonging to the Kunitz superfamily, are natural plant
      defense agents against pests and predators, and therefore are potential
      biopesticides for incorporation into pest-resistant crops. Here, a miraculin-like
      protein from Murraya koenigii was assessed for its in vitro and in vivo effects
      against two polyphagous lepidopteran insect pests, Helicoverpa armigera and
      Spodoptera litura. M. koenigii miraculin-like protein (MKMLP) inhibited the
      trypsin-like activity and total protease activity of H. armigera gut proteinases
      (HGP) by 78.5 and 40%, respectively, and S.litura gut proteinases (SGP) by 81 and
      48%, respectively. The inhibitor was stable and actively inhibited the
      proteolysis of both HGP and SGP enzymes for up to 72 h. Incorporation of MKMLP
      into artificial diet adversely affected the growth and development of pests in a
      dose-dependent manner. After 10 days of feeding on diets containing 200 uM MKMLP,
      larval weight was reduced to 69 and 44.8% and larval mortality was increased to
      40 and 43.3% for H. armigera and S litura, respectively. The LC(50) of MKMLP was
      0.34 and 0.22% of the diet for H.armigera and S. litura, respectively. These
      results demonstrate the efficacy of MKMLP as a potential plant defense agent
      against H. armigera and S. litura.

PMID- 21948664
TI  - [Ali El Okibi, resistance fighter during the German occupation].

PMID- 21948663
TI  - Plant growth and respiration re-visited: maintenance respiration defined - it is
      an emergent property of, not a separate process within, the system - and why the
      respiration : photosynthesis ratio is conservative.
AB  - BACKGROUND AND AIMS: Plant growth and respiration still has unresolved issues,
      examined here using a model. The aims of this work are to compare the model's
      predictions with McCree's observation-based respiration equation which led to the
      'growth respiration/maintenance respiration paradigm' (GMRP) - this is required
      to give the model credibility; to clarify the nature of maintenance respiration
      (MR) using a model which does not represent MR explicitly; and to examine
      algebraic and numerical predictions for the respiration:photosynthesis ratio.
      METHODS: A two-state variable growth model is constructed, with structure and
      substrate, applicable on plant to ecosystem scales. Four processes are
      represented: photosynthesis, growth with growth respiration (GR), senescence
      giving a flux towards litter, and a recycling of some of this flux. There are
      four significant parameters: growth efficiency, rate constants for substrate
      utilization and structure senescence, and fraction of structure returned to the
      substrate pool. KEY RESULTS: The model can simulate McCree's data on respiration,
      providing an alternative interpretation to the GMRP. The model's parameters are
      related to parameters used in this paradigm. MR is defined and calculated in
      terms of the model's parameters in two ways: first during exponential growth at
      zero growth rate; and secondly at equilibrium. The approaches concur. The
      equilibrium respiration:photosynthesis ratio has the value of 0.4, depending only
      on growth efficiency and recycling fraction. CONCLUSIONS: McCree's equation is an
      approximation that the model can describe; it is mistaken to interpret his second
      coefficient as a maintenance requirement. An MR rate is defined and extracted
      algebraically from the model. MR as a specific process is not required and may be
      replaced with an approach from which an MR rate emerges. The model suggests that
      the respiration:photosynthesis ratio is conservative because it depends on two
      parameters only whose values are likely to be similar across ecosystems.

PMID- 21948665
TI  - [Organ and tissue harvesting in children: comparison of the legal framework in
      Tunisia and France].
AB  - In Tunisia as in France, the legislator recognized the organ harvesting  as of
      public health priority. To promote it, cells of coordination are  created, and
      controlled by regulatory texts. There are differences in  the strategy of organ
      harvesting in minor but whether he is alive or  dead, he is well protected by
      law. Organ harvesting in alive child is  prohibited in both Tunisia and France
      but the haematopoietic cells one  is authorized. In the minor deceased organ
      harvesting obeys common  principles, appearing in the bioethical law (France) and
      the law n degrees 91-22  of March 25, 1991 (Tunisia) with a difference in the
      procedure of the  assent of the legal guardian.

PMID- 21948666
TI  - [A rare tumor of the nasal cavity: esthesioneuroblastoma].

PMID- 21948667
TI  - [Lipomatous pleomorphic adenoma of the hard palate].

PMID- 21948668
TI  - [Transverse testicular ectopia].

PMID- 21948669
TI  - [Traumatic popliteal artery pseudo aneurysm].

PMID- 21948670
TI  - Abdomino-pelvic actinomycosis associated with an intrauterine device.

PMID- 21948671
TI  - Raine syndrome.

PMID- 21948672
TI  - Ureteral stenosis due to Wegener's granulomatosis.

PMID- 21948673
TI  - [Infectious mononucleosis mimicking a lymphoma].

PMID- 21948674
TI  - [Fibromatosis of the breast in a male patient].

PMID- 21948675
TI  - [Unusual respiratory symptoms revealing relapsing polychondritis].

PMID- 21948676
TI  - A primary hydatid cyst of the gluteal muscle.

PMID- 21948677
TI  - [Acute intussusception in adults].

PMID- 21948678
TI  - [Intradiverticular tumors of the bladder: diagnostic and therapeutic problems:
      report of 32 cases].
AB  - BACKGROUND: The transitional cell carcinoma within the bladder diverticular is a
      rare and poorly known entity. AIM: To evaluate diagnostic and therapeutic
      approaches of transitional cell carcinoma within the bladder diverticular.
      METHODS: Thirty men and two women (median: 70 years; 44- 83 years) were included.
      The main reason for consultation was hematuria. The intra-diverticular tumor was
      suspected by radiological assessment in 9 patients only. All these patients
      underwent an endoscopic resection of the tumor. RESULTS: The histological study
      concluded to a pta stage in 16 patients, pt1 stage in 8 patients and invasive
      tumors in 8 patients. A complementary endovesical BCG-therapy was performed in
      patients with superficial tumors and a radical cystectomy in patients with
      invasive tumors. With an average follow-up of 27 months, seven recurrences were
      found in the group of superficial tumors, including 3 cases of progression to
      invasive stage. CONCLUSION: Bladder intra-diverticular tumors are rare and more
      common in elderly. In a bladder diverticulum, there are superficial tumors (pta,
      pt1) which are the most frequent and invasive tumors. Radical cystectomy is the
      gold standard for invasive tumors.Endoscopic resection combined with endo-vesical
      immunotherapy should be reserved for superficial tumors.

PMID- 21948679
TI  - [Obesity hypoventilation syndrome and obstructive sleep apnea syndrome: is there
      an association?].
AB  - BACKGROUND: Severe obesity sometimes leads to a chronic alveolar hypoventilation:
      obesity hypoventilation syndrome (OHS), (Pao2<70mmHG, Paco2>45mmHG and body mass
      index (BMI)>30Kg/m2). The association with an OSAS is frequent. AIM: To assess
      predicting factors that lead to hypoventilation in a population of obese patients
      with SAS and to deduct the type of association between OHS and SAS. METHODS: We
      have study during 4 years, at pneumology service of Charles Nicolle hospital, 62
      obese patients (BMI>30Kg /m2), 41men and 21 women and presenting an OSAS. We
      excluded those carriers of a bronchial obstruction (VEMS/CV <60%) and we have
      compared anthropometriques, functional, gazometriques and polysomographiques
      details of the groupe1 (G1): OHS=9 and of the groupe2 (G2): obesity without
      hypoventilation (n=53). RESULTS: We didn't identified any significant difference
      between the two groups concerning (age, sex, the frequency of smokers, the
      frequency of the nasopharynx region abnormalities, apnea-hypopnea index (AHI),
      the SAS severity and the respiratory functional exploration). The obesity is
      significant more important in the G1, it is sever (BMI>40) in 77.8% of patients
      of the G1 with significant difference with the G2 (P=0.004). We noted that there
      is a positive interrelationship between BMI and Paco2. We identified severe
      gazometrique perturbation in G1 (Pao2 medium = 61+/- 9 mmHg,Paco2 medium=50 +/- 7
      mmHg), in the G2 we noted a moderate hypoxemia. Patients of the group1 make of
      the minimal desaturation of 63 +/- 17% and a Sao2 average of 81 +/- 20% what is
      meaningfully more important than in the G2. CONCLUSION: The alveolar
      hypoventilation in SAS seems to be in correlation with the degree of obesity. The
      hypercapnie in the OHS is in relation neither with the SAOS nor with its
      severity. The OHSSAS association is usual but not synonym; the OHS is an
      autonomous disease.

PMID- 21948680
TI  - [Acute polyradiculoneuropathy in children: the Kairouan pediatric department
      experience. Report of 22 cases].
AB  - BACKGROUND: Guillain-Barre Syndrome (GBS) is an acute polyradidulonevritis which
      is primitive inflammatory and demyelinisant. It represents the most frequent
      cause of acute peripheric paralysis of the child. AIM: To study the
      epidemiologic, clinic, electromyographic, outcome and therapeutic features of
      this disease. METHODS: 22 cases of GBS were reported in the pediatric department
      of Ibn El Jazzar's hospital of Kairouan from January 1990 to September 2009.
      RESULTS: The GBS represents a hospital frequency of 0.45 %o . The mean age of the
      patients was 6.88 years with a sex ratio of 1.2. The prodromic infectious
      manifestations were observed in 54.5% of cases. The clinic symptomatology was the
      muscular deficiency observed in all cases with absence of deep reflex an
      albumincytologic dissociation was observed in 12 cases. The electromyographic
      manifestations were: an axonal disorder in four cases, axonomyelinic in eight
      cases and myelinic in seven cases. A specific therapy by intravenous polyvalent
      immunoglobulin was prescribed for 14 patients. The evolution was favourable in 10
      cases with total recovery three cases of drop foot gait were observed, seven
      patients were lost to follow up and two patients are dead. CONCLUSION: GB
      syndrome is the most frequent cause of child acute primitive distal paralysis,
      since acute polio has been eradicated. Acute Respiratory disorder is the most
      severe complication this syndrome can lead to in 5% of cases. The course of the
      disease is often mild and severe scars are only encountered in 5 to 10 % of
      cases. Indeed, the use intravenous immunoglobulin has utterly changed prognosis.

PMID- 21948681
TI  - [Clinicopathologic characteristics of low grade primary gastric non-Hodgkin's
      lymphomas: experience from a single center].
AB  - AIM: To report the clinicopathological data and the treatment outcomes in
      patients with primary gastric low grade non-Hodgkin's lymphoma. METHODS: We
      carried out a retrospective analysis of 16 consecutive patients (median age 46
      and range 28-75 years) who presented to our department with histopathological
      diagnosis of primary gastric low grade non-Hodgkin's lymphoma. We analyzed
      clinical manifestations, endoscopic features, pathological features,Helicobacter
      pylori infection and treatment. RESULTS: Common symptoms included abdominal pain
      (87.5%),vomiting (62.5%), and gastrointestinal bleeding (25%). Endoscopic
      appearances were mainly ulcers and ulcerations (93.75%).Endoscopic biopsy
      confirmation rate reached 87.5% when biopsies were repeated. Helicobacter pylori
      detection rate was 75%. A total of 9 patients received surgeries. Three patients
      had chemotherapy and 8 patients had Helicobacter pylori eradication therapy. The
      range of follow-up was 2-74 months with a median of 27 months. A complete
      remission was obtained in 12 cases, whereas 1 patient died and 3 were lost of
      view. CONCLUSION: Eradication therapy may be offered as an initial treatment
      option in patients with low-grade gastric lymphoma.

PMID- 21948682
TI  - [Outcome at 2 years of very premature infants. A Tunisian series].
AB  - BACKGROUND: Neurodevelopmental outcome of very premature infant can be associated
      with a high rate of cerebral palsy. AIM: To assess the impact of very preterm
      birth on neurological outcome at the age of two years. METHODS: Retrospective
      study of all cases of very premature infants born at less than 33 weeks of
      gestational age, during the years 2005 to 2007. Neurodevelopmental outcome is
      reported. RESULTS: During the study period, the very premature infant rate was
      1.5 %. A complete information about neurological outcome at the age of two years,
      was obtained in 60 cases.Eight infants (13.4%) showed major handicap (cerebral
      palsy) and four others infants developed neurosensoriel difficulties. CONCLUSION:
      The incidence of neurosensoriel handicap in our population seems relatively high.
      A strong effort must be made for identification of risk factors of
      neurodevelopmental disability.

PMID- 21948683
TI  - [Prospective study of the correlation of ultrasonography and CA125 in the
      management of ovarian cysts: a study of 77 cases].
AB  - AIM: To study the correlation between ultrasound, Doppler,measurement of CA 125
      and histology in the preoperative diagnosis of ovarian cysts. METHODS:
      Prospective and analytical study about 77 patients in whom we analyzed the
      contribution of ultrasound, the assay of CA125, the couple CA125 ultrasonography
      and laparoscopy in the diagnosis and management of cysts the ovary. The value of
      CA125 was considered pathological like the one adopted by our biochemistry
      laboratory of the CHU Habib Bourguiba, Sfax (> 35 UI / ml). RESULTS: The mean age
      was 35.6 years. On the whole, ultrasound has a sensitivity of 71.41% and a
      specificity of 80%. The positive predictive value was 35.71% and negative
      predictive value was 96.55%. The sensitivity of CA125 to detect malignant lesions
      among ovarian cysts was 85.71% and a specificity of 85.93%. The PPV was low
      (42.85%). The combination Ultrasound-CA125 had a sensitivity of 85.7%, a
      specificity of 82.8%, a PPV and NPV respectively 35.3% and 98.1%. The concordance
      between the macroscopic perlaparoscopic and histological diagnosis of different
      tumors was 83.3% for functional cysts, 77.7% for serous cysts, and 100% for
      dermoid cysts, endometriosis and bleeding. CONCLUSION: The contribution of
      Doppler ultrasound and tumor markers is essential in the diagnosis of ovarian
      cysts.

PMID- 21948684
TI  - [Long-term functional outcome of laparoscopic anti-reflux surgery].
AB  - BACKGROUND: Medical treatment of gastro esophageal reflux is associated with
      relapse in 30% of cases. In these patients, the best therapeutic option is
      surgical treatment, performed laparoscopically.However, there are few data on
      long-term functional outcome. AIM: To determine long-term results of laparoscopic
      antireflux surgery the mechanisms involved in patients with worse results.
      METHODS: We studied patients operated for reflux disease. They had either total
      or partial laparoscopic fundoplication. These patients were contacted to assess
      postoperative improvement, satisfaction and asked about the occurrence or not of
      a persistent postoperative dysphagia. RESULTS: Seventy one patients were included
      (Nissen in 61% of the cases and Toupet in 39%). After an average period of 52.4
      months,80 % of patients were satisfied. 58% were completely improved,while 31%
      were partially improved after surgery. Persistent reflux symptoms reflux were
      observed in 8 patients and postoperative dysphagia was reported by 11 patients.
      Gastroesophageal reflux revealed by chronic cough was the only independent
      parameter associated with bad functional results in our patients. CONCLUSION:
      Laparoscopic anti reflux surgery is associated with a high frequency of
      satisfaction. However, patients with chronic cough respond less better to
      surgery. Strict selection of the patients before surgery must be done, to improve
      the functional results after anti reflux surgery.

PMID- 21948685
TI  - [Totally implantable venous access ports by cephalic vein cut-down for patients
      receiving chemotherapy].
AB  - BACKGROUND: The use of an implantable room has become indispensable in the
      clinical practice for the cancer patients. The increasing use of these devices
      was associated with a greater incidence of complications. AIM: To verify the
      feasibility of the cephalic vein cut-down technique for placement of venous
      access devices. METHODS: A prospective study of 58 port placements was performed
      at our department of general surgery. The surveillance of devices was
      collectively insured by the operator and by the oncologists. RESULTS: The
      indication for implantation was the infusion of intravenous chemotherapy in
      patients with colorectal cancer in 55.1% cases and breast cancer in 27.5%. The
      specific complication rate was 7%. The cephalic vein cut-down approach was used
      successful in 45 (77.5%) patients. When the cephalic vein could not be used, a
      percutaneous technique was employed using the subclavian vein in 22.4% of the
      patients. CONCLUSION: Cephalic vein cut-down technique should be considered a
      safe and feasible approach for placement of venous access devices.

PMID- 21948686
TI  - [Oncological and functional results of 50 consecutive radical prostatectomies].
AB  - AIM: To evaluate the Oncological and functional results and to clear risk factors
      of biochemical recurrence in patients with prostate cancer treated by retropubic
      prostatectomy. METHODS: Retrospective analysis of 50 consecutive retropubic
      radical prostatectomies performed between January 1999 and january 2008.
      Biochemical recurrence was defined by PSA > 0.2 ng/ml. Univariate analysis of
      prognostic factors of biochemical recurrence was performed. The study of the
      urinary continence and the sexuality is essentially based on a meticulous
      interrogatory. RESULTS: The biochemical recurrence-free survival was 68%.
      Significant risk factors on univariate analysis were: number of positive biopsy,
      the percentage of positive biopsy, perineural invasion, Gleason score, clinical
      stage, pathological stage, and tumour volume. On the functional plan, only one
      patient is totally incontinent. The return to a normal sexuality appears
      uncertain, the sexual potency was satisfactory among 5 patients (10% of the
      patients operated and 55,5% of the patients having had a nervesparing techniques)
      CONCLUSION: Our oncological results is acceptable and are quite comparable to
      literature. This while guaranteeing the satisfactory functional results
      essentially basing on an acquirement of a continence quasi-perfect.

PMID- 21948687
TI  - Multispecific anti neutrophil cytoplasm antibodies: a case report.
AB  - AIM: To report the presence af ANCA with an unusual polyreactivity. CASE REPORT:
      50 year-old woman with pulmonary fibrosis whose immunological investigations
      showed the presence of ANCA with an unusual polyreactivity against several
      neutrophil proteins (PR3,MPO, BPI, lysozyme, elastase and cathepsine G) which
      could be related to a polyclonal hypergammaglobulinemia occurring in this
      patient. CONCLUSION: The international consensus on the testing of ANCA
      recommends seeking major specificities like MPO and PR3 which are good markers of
      ANCA-associated vasculitides. The use of multiantigenic ELISA can be helpful to
      detect various target antigens at the same time and may thus explain some
      atypical fluorescent patterns observed when searching for ANCA by Indirect
      immunofluorescence, these results, however, must be interpreted with caution.

PMID- 21948689
TI  - Characterization and potential applications of progenitor-like cells isolated
      from horse amniotic membrane.
AB  - The aim of this work was to isolate, for the first time, progenitor-like cells
      from the epithelial (AECs) and mesenchymal (AMCs) portions of the horse amniotic
      membrane, and to define the biological properties of these cells. AECs displayed
      polygonal epithelial morphology, while AMCs were fibroblast-like. Usually, six to
      eight passages were reached before proliferation decreased, with 13.08 and 26.5
      cell population doublings attained after 31 days for AECs and AMCs, respectively.
      Immunocytochemical studies performed at passage 3 (P3) showed that both cell
      populations were positive for the expression of specific embryonic markers (TRA-1
      60, SSEA-3, SSEA-4 and Oct-4). Meanwhile, RT-PCR performed at P1 and P5 showed
      expression of mesenchymal stem/stromal cell markers (CD29, CD105, CD44 and CD166)
      with negativity for CD34 at P1, although this marker began to be expressed by P5.
      The cells also expressed MHC-I at both P1 and P5, but lacked MHC-II expression at
      P1. Both AECs and AMCs demonstrated high plasticity, differentiating in vitro
      toward the osteogenic, adipogenic, chondrogenic and neurogenic lineages. Equine
      amnion-?derived cells could also be frozen and recovered without loss of their
      functional integrity in terms of morphology, presence of specific stemness
      markers and differentiation ability, although the renewal capacity was lower than
      that observed for freshly isolated cells. To investigate potential therapeutic
      effects and cell tolerance in vivo, horse amnion-derived cells were
      allogeneically injected into three horses with tendon injuries, resulting in a
      quick reduction in tendon size and ultrasonographic cross-sectional area
      measurements. These results suggest that horse amnion-derived cells may be useful
      for cell therapy applications.

PMID- 21948690
TI  - A functional nitroxide radical displaying unique thermochromism and magnetic
      phase transition.

PMID- 21948688
TI  - Increased re-entry into cell cycle mitigates age-related neurogenic decline in
      the murine subventricular zone.
AB  - Although new neurons are produced in the subventricular zone (SVZ) of the adult
      mammalian brain, fewer functional neurons are produced with increasing age. The
      age-related decline in neurogenesis has been attributed to a decreased pool of
      neural progenitor cells (NPCs), an increased rate of cell death, and an inability
      to undergo neuronal differentiation and develop functional synapses. The time
      between mitotic events has also been hypothesized to increase with age, but this
      has not been directly investigated. Studying primary-cultured NPCs from the young
      adult and aged mouse forebrain, we observe that fewer aged cells are dividing at
      a given time; however, the mitotic cells in aged cultures divide more frequently
      than mitotic cells in young cultures during a 48-hour period of live-cell time
      lapse imaging. Double-thymidine-analog labeling also demonstrates that fewer aged
      cells are dividing at a given time, but those that do divide are significantly
      more likely to re-enter the cell cycle within a day, both in vitro and in vivo.
      Meanwhile, we observed that cellular survival is impaired in aged cultures. Using
      our live-cell imaging data, we developed a mathematical model describing cell
      cycle kinetics to predict the growth curves of cells over time in vitro and the
      labeling index over time in vivo. Together, these data surprisingly suggest that
      progenitor cells remaining in the aged SVZ are highly proliferative.

PMID- 21948691
TI  - Maternally inherited partial monosomy 9p (pter -> p24.1) and partial trisomy 20p
      (pter -> p12.1) characterized by microarray comparative genomic hybridization.
AB  - We report on a 17-year-old patient with midline defects, ocular hypertelorism,
      neuropsychomotor development delay, neonatal macrosomy, and dental anomalies. DNA
      copy number investigations using a Whole Genome TilePath array consisting, of 30K
      BAC/PAC clones showed a 6.36 Mb deletion in the 9p24.1-p24.3 region and a 14.83
      Mb duplication in the 20p12.1-p13 region, which derived from a maternal balanced
      t(9;20)(p24.1;p12.1) as shown by FISH studies. Monosomy 9p is a well-delineated
      chromosomal syndrome with characteristic clinical features, while chromosome 20p
      duplication is a rare genetic condition. Only a handful of cases of monosomy
      9/trisomy 20 have been previously described. In this report, we compare the
      phenotype of our patient with those already reported in the literature, and
      discuss the role of DMRT, DOCK8, FOXD4, VLDLR, RSPO4, AVP, RASSF2, PROKR2, BMP2,
      MKKS, and JAG1, all genes mapping to the deleted and duplicated regions.

PMID- 21948692
TI  - Rapid testing of gene-gene interactions in genome-wide association studies of
      binary and quantitative phenotypes.
AB  - Genome-wide association (GWA) studies have been extremely successful in
      identifying novel loci contributing effects to a wide range of complex human
      traits. However, despite this success, the joint marginal effects of these loci
      account for only a small proportion of the heritability of these traits.
      Interactions between variants in different loci are not typically modelled in
      traditional GWA analysis, but may account for some of the missing heritability in
      humans, as they do in other model organisms. One of the key challenges in
      performing gene-gene interaction studies is the computational burden of the
      analysis. We propose a two-stage interaction analysis strategy to address this
      challenge in the context of both quantitative traits and dichotomous phenotypes.
      We have performed simulations to demonstrate only a negligible loss in power of
      this two-stage strategy, while minimizing the computational burden. Application
      of this interaction strategy to GWA studies of T2D and obesity highlights
      potential novel signals of association, which warrant follow-up in larger
      cohorts.

PMID- 21948693
TI  - Physical exercise for cancer patients with advanced disease: a randomized
      controlled trial.
AB  - BACKGROUND: Physical exercise can improve cancer patients' functioning and reduce
      their symptom levels. A randomized, controlled trial was launched to test the
      hypothesis that physical exercise reduces fatigue and improves physical
      performance in cancer patients with advanced and incurable disease. METHODS:
      Cancer patients (n = 231) with a life expectancy <=2 years were randomized to a
      physical exercise group (PEG, n = 121) or a control usual care group (UCG, n =
      110). The PEG exercised under supervision 60 minutes twice a week for 8 weeks.
      Assessments were performed before and after the intervention. The primary outcome
      was physical fatigue (PF) measured by the Fatigue Questionnaire. Physical
      performance was a secondary outcome measured by the Shuttle Walk Test (SWT) and
      hand grip strength (HGS) test. Analyses were performed after multiple imputations
      for missing data. The trial is registered with ClinicalTrials.gov (identifier,
      NCT00397774). FINDINGS: Thirty-six percent of the PEG were lost to follow-up
      compared with 23% of the UCG, primarily as a result of disease progression.
      Seventy-eight PEG and 85 UCG patients completed the intervention. Analyses showed
      no significant between-group effects in PF. However, clinically and statistically
      significant between-group effects were found for the SWT and HGS test.
      INTERPRETATION: Fatigue was not reduced but physical performance (SWT and HGS
      test) was significantly improved after 8 weeks of physical exercise. Physical
      exercise might therefore be a suitable approach for maintaining physical capacity
      in cancer patients with incurable and advanced disease.

PMID- 21948694
TI  - Endovascular management of bleeding events following robotic pancreaticobiliary
      surgery.
AB  - PURPOSE: To describe the utility, safety, and efficacy of endovascular
      intervention for treating bleeding events after robotic pancreaticobiliary
      surgery. MATERIALS AND METHODS: In this retrospective study, six patients
      (male/female, 3/3; mean age, 64 years) with histories of robotic
      pancreaticobiliary resection were referred for endovascular management of delayed
      postoperative intra-abdominal hemorrhage. Visceral angiography was performed, and
      the sites of suspected arterial hemorrhage were interrogated with selective
      microcatheter arteriography. The visualized bleeding sources were treated using
      catheter-directed embolotherapy with metallic coils, bare metal or covered stent
      insertion, or a combination of the two. The measured outcomes included the
      technical success of the angiographic occlusion, procedure safety, and procedure
      efficacy. RESULTS: Pseudoaneurysms resulted in bleeding in six cases (100%). The
      endovascular interventions included coil embolization in three cases (50%),
      covered stent exclusion in two cases (33%), and bare metal stent-assisted coil
      embolization in one case (17%). The technical success was 100%, with complete
      cessation of bleeding in all cases. No immediate or delayed procedure-related
      complications were encountered in any of the patients. The efficacy of the
      endovascular therapy was 100% in this series, with no recurrent hemorrhage during
      the mean clinical follow-up period of 262 days (range, 67-446 days). CONCLUSION:
      Endovascular therapy provides a minimally invasive, safe, and effective method
      for managing hemorrhagic events after complicated pancreaticobiliary surgery.

PMID- 21948695
TI  - Unusual malignant breast lesions: imaging-pathological correlations.
AB  - This pictorial essay presents the common radiological (mammography and/or    
      ultrasonography) and pathological findings observed in unusual malignant breast  
      lesions, which include well-differentiated subtypes of invasive ductal
      carcinoma     not otherwise specified (tubular, mucinous, papillary, and
      medullary     carcinomas), metaplastic carcinoma, and metastases. This study also
      includes     unusual ultrasonographic appearances of a plasmacytoma.

PMID- 21948696
TI  - Eosinophilic disorders of the gastrointestinal tract: imaging features.
AB  - Eosinophilic disorders of the gastrointestinal tract are increasingly rare but   
      remain an important cause of long-standing gastrointestinal symptoms. Diagnosis 
      is usually delayed because the disease mimics other inflammatory disorders and
      is often not suspected initially. We report a series of four cases to
      highlight     the various imaging appearances of this condition. Two patients
      presented with     upper gastrointestinal involvement, one patient presented with
      small and large     bowel involvement, and one patient presented with diffuse
      involvement of the     entire gastrointestinal tract.

PMID- 21948697
TI  - A patient with lung cancer metastatic to the fifth thoracic vertebra and spinal
      cord compression treated with percutaneous vertebroplasty and I-125 seed
      implantation.
AB  - Percutaneous vertebroplasty is a minimally invasive surgical technique for the   
      treatment of spinal damage and pathological compression fractures. Iodine-125   
      (I-125) particles can inhibit the uncontrolled proliferation of tumor cells to  
      achieve anti-tumor effects. We report treating a spinal cord compression and T5
      metastatic lung cancer patient through percutaneous vertebroplasty and I-125 
      seed implantation. Three years of follow-up demonstrated that our surgical
      plan     achieved a satisfactory clinical outcome with good postsurgical recovery
      of     spinal column function and relieved the symptoms of spinal cord
      compression.

PMID- 21948698
TI  - Ewing's sarcoma metastasis into the breast.
AB  - The metastasis of extramammary malignancies into the breast is very unusual.    
      Lymphoma, malignant melanoma, and rhabdomyosarcoma are the most common tumors    
      that metastasize into breast tissue. The histological spectrum of breast masses  
      in children and adolescents is different from that of adults. Imaging findings 
      are useful for performing a diagnosis, but in a patient with a known
      malignancy,     any enlarging breast mass, even one with a benign radiological
      appearance,     should be investigated with a biopsy. In this article, we present
      the imaging     findings of a 12-year-old female patient with breast metastasis
      of Ewing's     sarcoma.

PMID- 21948700
TI  - A novel automated cell-seeding device for tissue engineering of tubular
      scaffolds: design and functional validation.
AB  - Obtaining an efficient, uniform and reproducible cell seeding of porous tubular
      scaffolds constitutes a major challenge for the successful development of tissue
      engineered vascular grafts. In this study, a novel automated cell-seeding device
      utilizing direct cell deposition, patterning techniques and scaffold rotation was
      designed to improve the cell viability, uniformity and seeding efficiency of
      tubular constructs. Quantification methods and imaging techniques were used to
      evaluate these parameters on the luminal and abluminal sides of fibrous polymer
      scaffolds. With the automated seeding method, a high cell-seeding efficiency
      (~89%), viability (~85%) and uniformity (~85-92%) were achieved for both aortic
      smooth muscle cells (AoSMCs) and aortic endothelial cells (AoECs). The duration
      of the seeding process was < 8 min. Initial cell density, cell suspension in
      matrix-containing media, duration of seeding process and scaffold rotation were
      found to affect the seeding efficiency. After few days of culture, a uniform
      longitudinal and circumferential cell distribution was achieved without affecting
      cell viability. Both cell types were viable and spread along the fibres after 28
      h and 6 days of static incubation. This new automated cell-seeding method for
      tubular scaffolds is efficient, reliable and meets all the requirements for
      clinical applicability.

PMID- 21948701
TI  - Efficient hydrogen production from alcohols under mild reaction conditions.

PMID- 21948699
TI  - Phosphatase and tensin homolog regulates the pluripotent state and lineage fate
      choice in human embryonic stem cells.
AB  - Understanding the intrinsic and extrinsic signals that regulate the molecular
      basis of the pluripotent state may improve our understanding of mammalian
      embryogenesis, different states of pluripotency, and our ability to tailor
      lineage differentiation. Although the role of the PI3K/Akt pathway in the self
      renewal and maintenance of mESCs is well-established, the specific contribution
      of the pathway or of its negative regulator, PTEN, in the maintenance of the
      human pluripotent state is less understood. To explore the PI3K/AKT pathway in
      human embryonic stem cell (hESC) pluripotency and differentiation, we generated
      stable PTEN knockdown (KD) hESCs using short hairpin RNA. Similar to mESCs, we
      found that PTEN KD hESCs have increased self-renewal, cell survival, and
      proliferation over multiple passages compared to control cells. However, in
      contrast to mESCs, in vitro, PTEN KD hESCs differentiated inefficiently in
      directed differentiation assays, in part due to the continued maintenance of OCT4
      and NANOG expression. In teratoma assays, PTEN KD hESCs generated tissues from
      the three germ layers, although with a bias toward neuroectoderm differentiation.
      These results demonstrate that PTEN is a key regulator of hESC growth and
      differentiation, and manipulation of this pathway may improve our ability to
      regulate and understand the pluripotent state.

PMID- 21948702
TI  - Tibial hemimelia in Langer-Giedion syndrome with 8q23.1-q24.12 interstitial
      deletion.
AB  - Langer-Giedion syndrome (LGS) (OMIM 150230) is defined as a contiguous gene
      syndrome caused by loss of functional copies of the TRPS1 and EXT1 genes usually
      secondary to 8q microdeletion. Tibial hemimelia (TH) is the least common lower
      limb deficiency characterized by hypoplasia of the tibia with relatively intact
      fibula. We describe the third report of LGS with bilateral TH and an 8q23.1
      q24.12 interstitial deletion. It is not possible to exclude that this association
      is fortuitous, but our report reinforces the suggestion of a putative gene
      involved in limb development in this chromosomal region interval.

PMID- 21948703
TI  - Vitamin D supplementation during pregnancy.

PMID- 21948704
TI  - Hypoxia and neural stem cells: from invertebrates to brain cancer stem cells.
AB  - Oxygen is a fundamental element for all living organisms, and modifications in
      its concentration influence several physiological and pathological events such as
      embryogenesis, development and also aging. Regulation of oxygen levels is an
      important factor in neural stem cell biology (e.g. differentiation, growth and
      the capacity to generate more differentiated cells). Studies on neural stem cells
      in culture have deepened our knowledge of their survival, proliferation and
      differentiation pathways. However, traditional cell culture for neural stem cells
      is performed employing environmental oxygen levels of 20%, while the effective
      oxygen concentration in the developing and adult brain is significantly lower;
      this results in an important alteration of the in vivo conditions. Several data
      indicate that a so called "physiologic hypoxic condition" could strongly
      influence the growth of neural stem cells and their differentiation mechanisms
      both in vivo and in vitro. The present overview deals with the different
      mechanisms utilized by invertebrate and vertebrate organisms to respond to
      hypoxic conditions. It highlights how the adaptations and responses to different
      oxygen concentrations have changed along the developmental route and underlines
      the importance of oxygen concentration in neural physiology and differentiation,
      with a final hint to the involvement of hypoxia in brain cancer stem cells.

PMID- 21948705
TI  - Regulation and activity of JNK signaling in the wing disc peripodial membrane
      during adult morphogenesis in Drosophila.
AB  - Thorax closure in Drosophila is a process during adult morphogenesis in which the
      anterior ends of the presumptive notum of the two wing imaginal discs fuse to
      make a seamless thorax. Similar to dorsal closure during embryogenesis, this
      process is regulated by plegic and JNK signaling pathways. Despite the fact that
      Peripodial Membrane (PM) cells do not contribute to the formation of any adult
      structure, they are known to facilitate the process of thorax closure. Here we
      show that JNK signaling is activated only in a subset of PM cells, known as
      medial edge cells. While the mechanism that activates JNK signaling specifically
      in the medial edge cells of the PM is still not understood, the results presented
      here show that the pair rule gene odd skipped is required to ensure that JNK
      signaling is not activated anywhere else in the wing disc. Medial edge cells of
      the PM are elongated in shape, while the remaining PM cells are hexagonal. Down
      regulation of JNK signaling in the medial edge cells results in defective thorax
      closure in adult flies. It also causes the transformation of the morphology of
      medial edge cells into hexagonal shape. Conversely, activation of JNK signaling
      in hexagonal cells of the PM causes transformation of their morphology to
      elongated shape. Thus, similar to dorsal closure during embryogenesis, JNK
      mediated elongation of medial edge cells is functionally correlated to the
      process of thorax closure.

PMID- 21948706
TI  - Chromatin dynamics of the developmentally regulated P. lividus neural alpha
      tubulin gene.
AB  - Over 40 years ago, Allfrey and colleagues (1964) suggested that two histone
      modifications, namely acetylation and methylation, might regulate RNA synthesis.
      Nowadays it is universally accepted that activation of gene expression strictly
      depends on enzymatic mechanisms able to dynamically modify chromatin structure.
      Here, using techniques including DNaseI hypersensitive site analysis, chomatin
      immunoprecipitation and quantitative PCR analysis, we have analyzed the dynamics
      of histone post-translation modifications involved in developmentally/spatially
      controlled activation of the sea urchin PlTalpha2 tubulin gene. We have
      demonstrated that only when the PlTalpha2 core promoter chromatin is acetylated
      on H3K9, tri-methylated on H3K4 and not di-methylated on H3K27, RNA pol II can be
      enrolled. In contrast, we have shown that when chromatin is methylated both on
      H3K9 (me2/3) and H3K27 (me2) and mono methylated on H3K4 the promoter is not
      accessible to RNA pol II. Our results suggest that, during P. lividus
      embryogenesis, both HAT/HDAC and HMT/HDM activities, which are able to regulate
      accessibility of the PlTalpha2 basal promoter to RNA polymerase II, are
      coordinately switched-on.

PMID- 21948707
TI  - Opposing actions of histone deacetylase 1 and Notch signalling restrict
      expression of erm and fgf20a to hindbrain rhombomere centres during zebrafish
      neurogenesis.
AB  - The rate and pattern of neurogenesis in the developing vertebrate nervous system
      is controlled by a complex interplay of intercellular signalling pathways and
      transcriptional control mechanisms. In the zebrafish hindbrain, Fgf20a promotes
      transcription of the gene encoding the ETS-domain transcription factor Erm in the
      non-neurogenic centres of rhombomeres. Here, we demonstrate that the epigenetic
      regulator, Histone Deacetylase 1 (Hdac1) and the Notch signalling pathway have
      opposing functions in regulating expression of both erm and fgf20a in the
      zebrafish hindbrain. Our results show that Hdac1 is required for expression of
      erm and fgf20a in rhombomeres, and that the Hdac1-dependent expression of these
      two genes is attenuated in rhombomere boundary regions by Notch signalling
      activity, thereby restricting erm and fgf20a transcripts to narrow stripes of
      cells at rhombomere centres.

PMID- 21948708
TI  - Expression of the Scavenger Receptor Class B type I (SR-BI) family in Drosophila
      melanogaster.
AB  - In mammals, cholesterol is transformed into steroid hormones in the adrenal
      gland, the ovaries or the testes. The Scavenger Receptors Class B Type I (SR-BI)
      are membrane proteins that belong to the CD36 family and participate in the
      selective uptake of high density lipoprotein cholesteryl ester in the mammalian
      steroidogenic tissues. Fourteen members of the CD36 family have been identified
      in Diptera, although their expression patterns remain uncharacterized. Using in
      situ hybridization we have characterized the expression patterns of the fourteen
      SR-BIs in Drosophila melanogaster.  We analyzed three different developmental
      larval stages prior to and during the peak of the insect steroid hormone
      ecdysone, which triggers the larval to pupal transition. We focused on the
      steroidogenic tissues, such as the prothoracic gland, the ovaries and the testes,
      and extended our analysis to non-steroidogenic tissues, such as the fat body,
      salivary glands, the gut, the gastric caeca or the central nervous system. Our
      results show highly regulated expression patterns, with three genes crq, pes and
      Snmp being upregulated in steroidogenic tissues at the onset of pupariation when
      steroidogenesis is crucial. This study underlines the importance of the transport
      of cholesterol and steroids in the process of ecdysone synthesis.

PMID- 21948709
TI  - Zebrafish enhancer trap line recapitulates embryonic aquaporin 1a expression
      pattern in vascular endothelial cells.
AB  - Aquaporin 1 (Aqp1) is a water channel protein, expressed widely in microvascular
      endothelial cells and implicated in mammalian tumor angiogenesis. However, its
      developmental expression has not yet been characterized in great detail. An
      enhancer trap screen was performed using a Tol2-derived GFP reporter in zebrafish
      embryos.  An insertional Et(GBT-B1)tpl1 line was identified that has reporter
      insertion in the vicinity of the aqp1a gene. We further characterized the
      embryonic expression pattern of this GFP reporter line, as well as that of
      endogenous aqp1a. Both endogenous aqp1a and reporter GFP expression were
      restricted to the vascular endothelial cells within the dorsal aorta, cranial,
      intersegmental and other secondary vessels, but were absent in the axial venous
      vasculature. In addition, endogenous aqp1a expression was observed in both
      primitive and definitive hematopoietic erythroid progenitors, as well as in the
      otic vesicle, swim bladder, pneumatic duct, intestine and a subset of neurons
      within the retina and the midbrain-hindbrain region. We further show that gata1
      and etsrp/etv2 function is required for hematopoietic and endothelial aqp1a
      expression, respectively. Aqp1a expression is restricted to endothelial and
      erythroid cells during early embryogenesis. The transgenic Et(GBT-B1)tpl1 line
      recapitulates endogenous endothelial aqp1a expression. Because currently very few
      reporter lines can differentiate between arterial and venous endothelial cells,
      the Et(GBT-B1)tpl1 transgenic line and characterization of the aqp1a expression
      pattern will be useful for future studies of endothelial and arterial-venous
      differentiation.

PMID- 21948710
TI  - Differentiation of steroid-producing cells during ovarian differentiation in the
      protogynous Malabar grouper, Epinephelus malabaricus.
AB  - To understand the mechanism of sex differentiation in the protogynous Malabar
      grouper Epinephelus malabaricus, we performed an immunohistochemical
      investigation of the expression of three steroidogenic enzymes, cholesterol-side
      chain-cleavage enzyme (CYP11a), aromatase (CYP19a1a), and cytochrome P45011beta
      hydroxylase (CYP11b), in the gonads during ovarian differentiation. Strong
      positive immunoreactivity against CYP11a, the key enzyme of steroidogenesis, and
      CYP19a1a which is essential for estrogen (17beta-estradiol) production, appeared
      first in the somatic cells surrounding gonial germ cells in undifferentiated
      gonads and throughout ovarian differentiation. However, positive immunoreactivity
      against CYP11b, which is important for androgen (11-ketotestosterone) production,
      first appeared in the cluster of somatic cells in the ovary tunica near the
      dorsal blood vessel after differentiation. CYP19a1a and CYP11b did not co
      localize in any cells. These results indicate that there are two types of steroid
      producing cells, estrogen-producing cells and androgen-producing cells, in the
      gonads of this fish, and they are distributed differently, suggesting that these
      cells are derived from different somatic cells. Estrogen-producing cells appeared
      prior to ovarian differentiation, while androgen-producing cells were first
      detected after ovarian differentiation. These results suggest that endogenous
      estrogen is involved in ovarian differentiation.

PMID- 21948711
TI  - Temporal and spatial expression patterns of Cdc25 phosphatase isoforms during
      early Xenopus development.
AB  - In early animal development, cell proliferation and differentiation are tightly
      linked and coordinated. It is important, therefore, to know how the cell cycle is
      controlled during early development. Cdc25 phosphatases activate cyclin-dependent
      kinases (Cdks) and thereby promote cell-cycle progression. In Xenopus laevis,
      three isoforms of cdc25 have been identified, viz. cdc25A, cdc25B and cdc25C. In
      this study, we isolated a cDNA encoding a novel Xenopus Cdc25 phosphatase (named
      cdc25D). We investigated the temporal and spatial expression patterns of the four
      cdc25 isoforms during early Xenopus development, using RT-PCR and whole-mount in
      situ hybridization. cdc25A and cdc25C were expressed both maternally and
      zygotically, whereas cdc25B and cdc25D were expressed zygotically. Both cdc25A
      and cdc25C were expressed mainly in prospective neural regions, whereas cdc25B
      was expressed preferentially in the central nervous system (CNS), such as the
      spinal cord and the brain. Interestingly, cdc25D was expressed in the epidermal
      ectoderm of the late-neurula embryo, and in the liver diverticulum endoderm of
      the mid-tailbud embryo. In agreement with the spatial expression patterns in
      whole embryos, inhibition of bone morphoge- netic protein (BMP), a crucial step
      for neural induction, induced an upregulation of cdc25B, but a downregulation of
      cdc25D in animal cap assays.These results indicate that different cdc25 isoforms
      are differently expressed and play different roles during early Xenopus
      development.

PMID- 21948712
TI  - Decorin developmental expression and function in the early avian embryo.
AB  - Decorin, a proteoglycan, interacts with extracellular matrix proteins, growth
      factors and receptors. Decorin expression and spatio-temporal distribution were
      studied by RT-PCR and immunofluorescence, while decorin function was examined by
      blocking antibodies in the early chick embryo. Decorin was first detectable at
      stage XIII (late blastula). During gastrulation (stage HH3-4), decorin
      fluorescence was intense in epiblast cells immediately adjacent to the streak,
      and in migrating cells. Decorin fluorescence was intense in endoderm and strong
      at mesoderm-neural plate surfaces at stage HH5-6 (neurula). At stage HH10-11 (12
      somites), decorin fluorescence was intense in myelencephalon and then showed
      distinct expression patterns along the myelencephalon axes by stage HH17. Decorin
      fluorescence was intense in neural crest cells, dorsal aorta, heart, somite and
      neuroepithelial cells apposing the somite, nephrotome, gut and in pancreatic and
      liver primordia. Antibody-mediated inhibition of decorin function affected the
      head-to-tail embryonic axis extension, indicating that decorin is essential for
      convergent extension cell movements during avian gastrulation. Decorin was also
      essential for retinal progenitor cell polarization, neural crest migration,
      somite boundary formation and cell polarization, mesenchymal cell polarization
      and primary endoderm displacement to the embryo periphery. The embryonic blood
      vessels were deformed, the dorsal mesocardium was thinned and the cardiac jelly
      was abnormally thickened in the heart. Decorin is known to modulate collagen
      fibrillogenesis, a key mechanism of matrix assembly, and cell proliferation.
      Decorin also appears to be essential for the coordination of cell and tissue
      polarization, which is an important feature in organ patterning of the embryo.

PMID- 21948713
TI  - Cytoskeletal heart-enriched actin-associated protein (CHAP) is expressed in
      striated and smooth muscle cells in chick and mouse during embryonic and adult
      stages.
AB  - We recently identified a new Z-disc protein, CHAP (Cytoskeletal Heart-enriched
      Actin-associated Protein), which is expressed in striated muscle and plays an
      important role during embryonic muscle development in mouse and zebrafish. Here,
      we confirm and further extend these findings by (i) the identification and
      characterization of the CHAP orthologue in chick and (ii) providing a detailed
      analysis of CHAP expression in mouse during embryonic and adult stages. Chick
      CHAP contains a PDZ domain and a nuclear localization signal, resembling the
      human and mouse CHAPa. CHAP is expressed in the developing heart and somites, as
      well as muscle precursors of the limb buds in mouse and chick embryos. CHAP
      expression in heart and skeletal muscle is maintained in adult mice, both in slow
      and fast muscle fibers. Moreover, besides expression in striated muscle, we
      demonstrate that CHAP is expressed in smooth muscle cells of aorta, carotid and
      coronary arteries in adult mice, but not during embryonic development.

PMID- 21948714
TI  - Reproductive Meristem22 is a unique marker for the early stages of stamen
      development.
AB  - Stamens undergo a very elaborate development program that gives rise not only to
      many specific tissue types, but also to the male gametes. The specification of
      stamen identity is coordinated by a group of homeotic genes such as APETALA3
      (AP3) and PISTILLATA (PI), AGAMOUS (AG) and SEPALLATA (SEP1-4)  genes. Genome
      wide transcriptomic comparisons between floral buds of wild-type and ap3 mutants
      led to the identification of the REM22 gene, which is expressed in the early
      stages of stamen development. This gene is member of the plant-specific B3 DNA
      binding superfamily. In this work, we dissect the spatio-temporal expression
      pattern of REM22 during the early stages of stamen development. To this end, both
      in situ hybridization analyses as well as in vivo fluorescence strategies were
      employed. At stage 4 of flower development, REM22 is expressed exclusively in
      those undifferentiated cells of the floral meristem that will give rise to the
      stamen primordia. At stage 5, REM22 expression is restricted to the epidermal and
      the subepidermal layers of anther primordia. Later, this expression is confined
      to the middle layer and the differentiating tapetal cells. After stage 10 when
      all the tissues of the anther have differentiated, REM22 expression is no longer
      detectable. Furthermore, we examined the pREM22::GUS-GFP marker line in an
      inducible system where the ectopic AG function is used to promote
      microsporogenesis. The data support the idea that REM22 expression is a useful
      marker to study the early stages of stamen development.

PMID- 21948715
TI  - Contraction-induced Mmp13 and -14 expression by goat articular chondrocytes in
      collagen type I but not type II gels.
AB  - Collagen gels are promising scaffolds to prepare an implant for cartilage repair
      but several parameters, such as collagen concentration and composition as well as
      cell density, should be carefully considered, as they are reported to affect
      phenotypic aspects of chondrocytes. In this study we investigated whether the
      presence of collagen type I or II in gel lattices affects matrix contraction and
      relative gene expression levels of matrix proteins, MMPs and the subsequent
      degradation of collagen by goat articular chondrocytes. Only floating collagen I
      gels, and not those attached or composed of type II collagen, contracted during a
      culture period of 12 days. This coincided with an upregulation of both Mmp13 and 
      14 gene expression, whereas Mmp1 expression was not affected. The release of
      hydroxyproline in the culture medium, indicating matrix degradation, was
      increased five-fold in contracted collagen I gels compared to collagen II gels
      without contraction. Furthermore, blocking contraction of collagen I gels by
      cytochalasin B inhibited Mmp13 and -14 expression and the release of
      hydroxyproline. The expression of cartilage-specific ECM genes was decreased in
      contracted collagen I gels, with increased numbers of cells with an elongated
      morphology, suggesting that matrix contraction induces dedifferentiation of
      chondrocytes into fibroblast-like cells. We conclude that the collagen
      composition of the gels affects matrix contraction by articular chondrocytes and
      that matrix contraction induces an increased Mmp13 and -14 expression as well as
      matrix degradation.

PMID- 21948716
TI  - The missing elements of the noncommunicable diseases action plan.

PMID- 21948717
TI  - A breast mass in a 56-year-old man.

PMID- 21948718
TI  - UN summit urges more accountability within food and beverage industry.

PMID- 21948720
TI  - Every physician a psychoanalyst? Implications of the Adverse Childhood
      Experiences study.

PMID- 21948719
TI  - Risk of bleeding associated with combined use of selective serotonin reuptake
      inhibitors and antiplatelet therapy following acute myocardial infarction.
AB  - BACKGROUND: Patients prescribed antiplatelet treatment to prevent recurrent acute
      myocardial infarction are often also given a selective serotonin reuptake
      inhibitor (SSRI) to treat coexisting depression. Use of either treatment may
      increase the risk of bleeding. We assessed the risk of bleeding among patients
      taking both medications following acute myocardial infarction. METHODS: We
      conducted a retrospective cohort study using hospital discharge abstracts,
      physician billing information, medication reimbursement claims and demographic
      data from provincial health services administrative databases. We included
      patients 50 years of age or older who were discharged from hospital with
      antiplatelet therapy following acute myocardial infarction between January 1998
      and March 2007. Patients were followed until admission to hospital due to a
      bleeding episode, admission to hospital due to recurrent acute myocardial
      infarction, death or the end of the study period. RESULTS: The 27,058 patients in
      the cohort received the following medications at discharge: acetylsalicylic acid
      (ASA) (n = 14,426); clopidogrel (n = 2467), ASA and clopidogrel (n = 9475); ASA
      and an SSRI (n = 406); ASA, clopidogrel and an SSRI (n = 239); or clopidogrel and
      an SSRI (n = 45). Compared with ASA use alone, the combined use of an SSRI with
      antiplatelet therapy was associated with an increased risk of bleeding (ASA and
      SSRI: hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.08-1.87; ASA,
      clopidogrel and SSRI: HR 2.35, 95% CI 1.61-3.42). Compared with dual antiplatelet
      therapy alone (ASA and clopidogrel), combined use of an SSRI and dual
      antiplatelet therapy was associated with an increased risk of bleeding (HR 1.57,
      95% CI 1.07-2.32). INTERPRETATION: Patients taking an SSRI together with ASA or
      dual antiplatelet therapy following acute myocardial infarction were at increased
      risk of bleeding.

PMID- 21948721
TI  - Brazilian health care faces harsh choices.

PMID- 21948724
TI  - Foster Kennedy syndrome: papilledema in one eye with optic atrophy in the other
      eye.

PMID- 21948723
TI  - San Francisco Syncope Rule to predict short-term serious outcomes: a systematic
      review.
AB  - BACKGROUND: The San Francisco Syncope Rule has been proposed as a clinical
      decision rule for risk stratification of patients presenting to the emergency
      department with syncope. It has been validated across various populations and
      settings. We undertook a systematic review of its accuracy in predicting short
      term serious outcomes. METHODS: We identified studies by means of systematic
      searches in seven electronic databases from inception to January 2011. We
      extracted study data in duplicate and used a bivariate random-effects model to
      assess the predictive accuracy and test characteristics. RESULTS: We included 12
      studies with a total of 5316 patients, of whom 596 (11%) experienced a serious
      outcome. The prevalence of serious outcomes across the studies varied between 5%
      and 26%. The pooled estimate of sensitivity of the San Francisco Syncope Rule was
      0.87 (95% confidence interval [CI] 0.79-0.93), and the pooled estimate of
      specificity was 0.52 (95% CI 0.43-0.62). There was substantial between-study
      heterogeneity (resulting in a 95% prediction interval for sensitivity of 0.55
      0.98). The probability of a serious outcome given a negative score with the San
      Francisco Syncope Rule was 5% or lower, and the probability was 2% or lower when
      the rule was applied only to patients for whom no cause of syncope was identified
      after initial evaluation in the emergency department. The most common cause of
      false-negative classification for a serious outcome was cardiac arrhythmia.
      INTERPRETATION: The San Francisco Syncope Rule should be applied only for
      patients in whom no cause of syncope is evident after initial evaluation in the
      emergency department. Consideration of all available electrocardiograms, as well
      as arrhythmia monitoring, should be included in application of the San Francisco
      Syncope Rule. Between-study heterogeneity was likely due to inconsistent
      classification of arrhythmia.

PMID- 21948726
TI  - FDA panel recommends approval of deferiprone.

PMID- 21948727
TI  - Current issues with prediction rules for syncope.

PMID- 21948728
TI  - Centralized, nationwide electronic health records schemes under assault.

PMID- 21948730
TI  - Neo-confused porphyrins, a new class of porphyrin isomers.

PMID- 21948729
TI  - Urbanisation, asthma and allergies.

PMID- 21948732
TI  - Circulation times of prostate cancer and hepatocellular carcinoma cells by in
      vivo flow cytometry.
AB  - In metastasis, the cancer cells that travel through the body are capable of
      establishing new tumors in locations remote from the site of the original
      disease. To metastasize, a cancer cell must break away from its tumor and invade
      either the circulatory or lymphatic system, which will carry it to a new
      location, and establish itself in the new site. Once in the blood stream, the
      cancer cells now have access to every portion of the body. Here, we have used the
      "in vivo flow cytometer" to study if there is any relationship between metastatic
      potential and depletion kinetics of circulating tumor cells. The in vivo flow
      cytometer has the capability to detect and quantify continuously the number and
      flow characteristics of fluorescently labelled cells in vivo. We have improved
      the counting algorithm and measured the depletion kinetics of cancer cells with
      different metastatic potential. Interestingly, more invasive PC-3 prostate cancer
      cells are depleted faster from the circulation than LNCaP cells. In addition, we
      have measured the depletion kinetics of two related human hepatocellular
      carcinoma (liver cancer) cell lines, high-metastatic HCCLM3 cells, and low
      metastatic HepG2 cells. More than 60% HCCLM3 cells are depleted within the first
      hour. Interestingly, the low-metastatic HepG2 cells possess noticeably slower
      depletion kinetics. In comparison, <40% HepG2 cells are depleted within the first
      hour. The differences in depletion kinetics might provide insights into early
      metastasis processes.

PMID- 21948731
TI  - In vivo photoacoustic and photothermal cytometry for monitoring multiple blood
      rheology parameters.
AB  - Alterations of blood rheology (hemorheology) are important for the early
      diagnosis, prognosis, and prevention of many diseases, including myocardial
      infarction, stroke, sickle cell anemia, thromboembolism, trauma, inflammation,
      and malignancy. However, real-time in vivo assessment of multiple hemorheological
      parameters over long periods of time has not been reported. Here, we review the
      capabilities of label-free photoacoustic (PA) and photothermal (PT) flow
      cytometry for dynamic monitoring of hemorhelogical parameters in vivo which we
      refer to as photoacoustic and photothermal blood rheology. Using phenomenological
      models, we analyze correlations between both PT and PA signal characteristics in
      the dynamic modes and following determinants of blood rheology: red blood cell
      (RBC) aggregation, deformability, shape (e.g., as in sickle cells), intracellular
      hemoglobin distribution, individual cell velocity, hematocrit, and likely shear
      rate. We present ex vivo and in vivo experimental verifications involving high
      speed PT imaging of RBCs, identification of sickle cells in a mouse model of
      human sickle cell disease and in vivo monitoring of complex hemorheological
      changes (e.g., RBC deformability, hematocrit and RBC aggregation). The multi
      parameter platform that integrates PT, PA, and conventional optical techniques
      has potential for translation to clinical applications using safe, portable,
      laser-based medical devices for point-of-care screening of disease progression
      and therapy efficiency.

PMID- 21948734
TI  - Results.

PMID- 21948736
TI  - Benefits of custom-made foot orthoses in treating patellofemoral pain.
AB  - BACKGROUND: Patellofemoral pain is one of the most common disorders affecting the
      knee. Forefoot varus and excessive subtalar pronation can be associated with
      patellofemoral pain. Foot orthotics may produce an improvement in symptoms.
      OBJECTIVES: The aim of this study was to test whether patellofemoral pain is
      improved after four weeks of using custom-made foot orthoses. STUDY DESIGN:
      Clinical trial without control group. METHODS: Twenty-one subjects with
      patellofemoral pain were given custom-made foot orthoses (2-mm thick
      polypropylene and 4-mm thick polyethylene foam liner of 45 shore A hardness).
      Patellofemoral pain was evaluated with a visual analogue scale before applying
      the treatment, and at two weeks and four weeks follow-up. At the two-week check
      up, a forefoot varus posting was added to the orthoses. RESULTS: Improvements in
      patellofemoral pain was significant in all comparisons: initial pain with pain at
      the two-week check-up (P < 0.001), initial pain with pain at four weeks (P <
      0.001), and pain at two weeks with pain at four weeks (P < 0.001). The effect
      size was large in all comparisons. CONCLUSION: For the participants in this
      study, the custom-made foot orthoses were found to be an effective conservative
      treatment to reduce the symptoms of patellofemoral pain.

PMID- 21948737
TI  - Change of rocker function in the gait of stroke patients using an ankle foot
      orthosis with an oil damper: immediate changes and the short-term effects.
AB  - BACKGROUND: An ankle foot orthosis (AFO) using an oil damper (AFO-OD) to assist
      the first rocker during gait was previously developed but the effect on the other
      rocker functions has not been clarified. OBJECTIVES: The immediate and short-term
      effects on the gait of stroke patients with the AFO-OD were investigated from the
      viewpoint of the rocker function. STUDY DESIGN: Crossover study. METHODS: The
      gait of eight stroke patients in chronic phase without an AFO, with the AFO-OD,
      and the gait with AFO-OD after three weeks of continuous use and gait training
      were measured by 3D motion analysis. RESULTS: Immediate changes observed on use
      of the AFO-OD were improvements in walking speed, the spatiotemporal parameters,
      and the angular change of dorsiflexion of the ankle joint. Three weeks of
      continuous AFO-OD use and gait training showed further improvements in walking
      speed and the spatiotemporal parameters as well as an increase in dorsiflexion
      angle and plantar flexor moment of the ankle joint of the paretic limb in stance.
      CONCLUSIONS: These changes produced improvement of the second rocker function,
      but improvement of the third rocker was insufficient. Results show the importance
      of gait training to take full advantage of an AFO.

PMID- 21948738
TI  - Adipocyte is a non-trivial, dynamic partner of breast cancer cells.
AB  - While the participation of adipocytes is well known in tissue architecture,
      energy supply and endocrine processes, their implication during natural cancer
      history is just beginning to unfold. An extensive review of the literature
      concerning the impact of resident adipocytes on breast cancer
      development/progression was performed. This review provides in vitro and in vivo
      evidence that adipocytes located close to invasive cancer cells, referred to as
      cancer-associated adipocytes (CAAs), are essential for breast tumor
      development/progression. Their deleterious function is dependent, at least
      partly, on their crosstalk with invasive cancer cells. Indeed, this event leads
      to dramatic phenotypic and/or functional modifications of both cell types.
      Adipocytes exhibit delipidation and acquire a fibroblast-like shape. In parallel,
      cancer cell aggressiveness is exacerbated through increased migratory and
      invasive properties. Moreover, obesity is currently a sign of poor prognosis in
      human carcinomas. In this context, a high number of "obese" resident adipocytes
      might be predicted to be detrimental. Accordingly, there are some similarities
      between the molecular alterations observed in hypertrophied adipocytes and in
      CAAs. How adipocytes function to favor tumorigenesis at the molecular level
      remains largely unknown. Nevertheless, progress has been made recently and
      molecular clues are starting to emerge. Deciphering the cellular and molecular
      mechanisms behind the adipocyte-cancer cell heterotypic crosstalk is of great
      interest since it might provide new targets for improving diagnosis/prognosis and
      for the design of innovative therapeutic strategies. They might also improve our
      understanding of the relationship between obesity/metabolic disorders and cancer
      risk and/or poor patient outcome.

PMID- 21948739
TI  - The mammary myoepithelial cell.
AB  - Over the last few years, the discovery of basal-type mammary carcinomas and the
      association of the regenerative potential of the mammary epithelium with the
      basal myoepithelial cell population have attracted considerable attention to this
      second major mammary lineage. However, many questions concerning the role of
      basal myoepithelial cells in mammary morphogenesis, functional differentiation
      and disease remain unanswered. Here, we discuss the mechanisms that control the
      myoepithelial cell differentiation essential for their contractile function,
      summarize new data concerning the roles played by cell-extracellular matrix
      (ECM), intercellular and paracrine interactions in the regulation of various
      aspects of the mammary basal myoepithelial cell functional activity. Finally, we
      analyze the contribution of the basal myoepithelial cells to the regenerative
      potential of the mammary epithelium and tumorigenesis.

PMID- 21948740
TI  - Synthesis of 1-phospha-2-boraacenaphthenes: reductive 1,2-aryl migration of 1
      diarylboryl-8-dichlorophosphinonaphthalenes.

PMID- 21948741
TI  - The reactivity of nano silica with calcium hydroxide.
AB  - The reactivity of nano silica (SiO2) with calcium hydroxide (Ca(OH)2) was
      evaluated and characterized in this study. Ca(OH)2 activated nano SiO2 takes
      place through an exothermic process, which is mainly attributed to the breakdown
      of Si-O-Si bonds. Ca(2+) offsets the charge imbalance and bonds to Si-OH and Si
      O(-) giving rise to calcium silicate hydrate (CSH) gel. Care has to be taken that
      the reactivity of nano SiO2 with Ca(OH) 2significantly depends on the Q3
      percentage in nano SiO 2. Q3 percentages significantly influence the reaction
      kinetic of nano SiO2 . The higher Q3 percentage results in a higher reaction
      degree of nano SiO2 with Ca(OH)2 and shorter setting times of the pastes. The
      higher Q3 percentage results in a lower total reaction heat of nano SiO2 with
      Ca(OH)2. It is suggested that the Q3 percentages of nano SiO2 should be in excess
      of 30% to keep the satisfactory setting properties of the pastes for the
      application requirements of bone cement.

PMID- 21948742
TI  - Anatomy and aging of the amygdala and hippocampus in autism spectrum disorder: an
      in vivo magnetic resonance imaging study of Asperger syndrome.
AB  - It has been proposed that people with autism spectrum disorder (ASD) have
      abnormal morphometry and development of the amygdala and hippocampus (AH).
      However, previous reports are inconsistent, perhaps because they included people
      of different ASD diagnoses, ages, and health. We compared, using magnetic
      resonance imaging, the in vivo anatomy of the AH in 32 healthy individuals with
      Asperger syndrome (12-47 years) and 32 healthy controls who did not differ
      significantly in age or IQ. We measured bulk (gray + white matter) volume of the
      AH using manual tracing (MEASURE). We first compared the volume of AH between
      individuals with Asperger syndrome and controls and then investigated age-related
      differences. We compared differences in anatomy before, and after, correcting for
      whole brain size. There was no significant between group differences in whole
      brain volume. However, individuals with Asperger syndrome had a significantly
      larger raw bulk volume of total (P<0.01), right (P<0.01), and left amygdala
      (P<0.05); and when corrected for overall brain size, total (P<0.05), and right
      amygdala (P<0.01). There was a significant group difference in aging of left
      amygdala; controls, but not individuals with Asperger syndrome, had a significant
      age-related increase in volume (r = 0.486, P<0.01, and r = 0.007, P = 0.97, z =
      1.995). There were no significant group differences in volume or age-related
      effects in hippocampus. Individuals with Asperger syndrome have significant
      differences from controls in bulk volume and aging of the amygdala.

PMID- 21948743
TI  - Genetic  analysis of NaCl tolerance in tomato.
AB  - We attempted to find the suitable parents  for the development of tomato hybrids
      for high salt soils by exploiting  combining ability, gene action and heterosis.
      Six salt-tolerant and three  salt-intolerant genotypes, along with their 18 F1
      crosses, were evaluated at  seedling stage under 10 and 15 dS/m (NaCl) salinity
      stress, compared to the  control level of salinity. The experiment was laid out
      based on a two-way  complete randomized design factorial arrangement with two
      replications; data on  root and shoot length, fresh and dry weights, leaf area,
      plant length, Na(+), K(+) and K(+)/Na(+) concentrations were recorded. There was 
      significant variation within genotypes, lines, testers, crosses, and line * 
      tester interaction for all plant characters studied under normal and two salinity
      levels. Estimates of combining ability indicated that under low (10 dS/m) and 
      high (15 dS/m) salinities, line BL1176 and tester LO2875 showed significant GCA 
      effects for most of the traits studied. The cross-combinations 6233 * LO2875, 
      CLN2498A x LO2875 and BL1176 * 17902 showed highest SCA values for most of the 
      characters under 10 and 15 dS/m, respectively. Potence ratio showed that under 
      low and high salinities, all the traits showed over dominant type of gene  action
      except leaf area and K(+)  concentration (in 10  dS/m) and shoot length, and leaf
      area (in 15 dS/m). The highest heterosis for  most of the parameters was observed
      in cross-combinations BL1176 * LO2875 and  CLN2498A x LO2875.

PMID- 21948744
TI  - Molecular cloning, characterization and association analysis of the promoter
      region of the bovine CDK6 gene.
AB  - Cyclin-dependent kinase 6 (CDK6) is a key element of D-type cyclin holoenzymes.
      It is involved in the regulation of the G1-phase of the cell cycle and is
      considered to be an important candidate gene for selection of body measurement
      traits through marker-assisted selection. We cloned the promoter sequence of this
      gene in bovines and found it to share high similarity with that of the human CDK6
      promoter. A 2271-bp sequence upstream of the start codon in the bovine CDK6 5'
      flanking sequence is rich in GC; it lacks consensus TATA or CAAT box, but it
      contains several MZF1 binding sites. Other potential cis-regulatory elements were
      found in the 5'-flanking region, including CdxA, SRY, p300, GATA-1, and deltaE.
      Allele frequencies were also analyzed in various cattle breeds (Qinchuan,
      Qinchuan improvement steers, Nanyang, Jiaxian red, Xia'nan, Luxi, Simmental and
      Luxi crossbred steers, and Xuelong) and association with a selected single
      nucleotide polymorphism (SNP) was calculated. The T-1075C SNP in the promoter was
      found to be significantly associated with body length and heart girth. This SNP
      marker was found to be significantly associated with body length and the heart
      girth in 737 individuals. We conclude that this SNP of the CDK6 gene has
      potential as a genetic marker for important body traits in bovine reproduction
      and breeding.

PMID- 21948745
TI  - Proteomic and bioinformatic analysis of outer membrane proteins of the
      protobacterium Bartonella henselae (Bartonellaceae).
AB  - Bartonella henselae, an infectious agent causing cat-scratch disease and 
      vasculoproliferative disorders in humans, is a fastidious facultative 
      intracellular pathogen. The outer membrane proteins of B. henselae are  key
      molecules that play a primary role in host-cell interactions. We isolated B. 
      henselae outer membrane proteins, using the ionic detergent N-lauroyl  sarcosine
      sodium salt and sodium carbonate, purification by two-dimensional  (2-D) gel
      electrophoresis, and protein identification using mass spectrometry.  Treatment
      with buffers containing ASB-14 and ZWITTERGENT 3-10 increased  solubilization of
      B. henselae proteins, particularly proteins with  basic pI. Three hundred and
      sixty-eight spots were detected from the  sarcosine-insoluble outer membrane
      fraction; 94 distinct protein species were  identified from 176 spots. In the
      outer membrane fraction from carbonate  incubation, 471 spots were calculated and
      259 spots were identified, which  included 139 protein entries. There were six
      outer membrane proteins in the  sarcosine-insoluble outer membrane fraction
      compared with nine outer membrane  proteins from samples subjected to carbonate
      incubation. We used bioinformatic  analysis to identify 44 outer membrane
      proteins by prediction of their domains  and tertiary structures and documented
      the potential virulence factors. We  established the 2-D reference maps of the
      outer membrane subproteome of B.  henselae using the two different extraction
      methods, which were partly  complementary to each other. Sodium carbonate
      extraction isolated low-abundance  and basic proteins better than the lauroyl
      sarcosine sodium salt extraction,  which enriched high-abundance porins.

PMID- 21948746
TI  - Single nucleotide polymorphisms in the growth hormone and insulin-like growth
      factor-1 genes are associated with milk production, body condition score and
      fertility traits in dairy cows.
AB  - The somatotrophic axis (GH-IGF) is a key regulator of  animal growth and
      development, affecting performance traits that include milk  production, growth
      rate, body composition, and fertility. The aim of this study  was to quantify the
      association of previously identified SNPs in bovine growth  hormone (GH1) and
      insulin-like growth factor 1 (IGF-1) genes with  direct performance trait
      measurements of lactation and fertility in  Holstein-Friesian lactating dairy
      cows. Sixteen SNPs in both IGF-1 and GH1 were genotyped across 610 cows and
      association analyses were carried out  with traits of economic importance
      including calving interval, pregnancy rate to  first service and 305-day milk
      production, using animal linear mixed models  accounting for additive genetic
      effects. Two IGF-1 SNPs, IGF1i1 and IGF1i2, were significantly associated with
      body condition score at  calving, while a single IGF-1 SNP, IGF1i3, was
      significantly  associated with milk production, including milk yield (means +/-
      SEM; 751.3 +/-  262.0 kg), fat yield (21.3 +/- 10.2 kg) and protein yield (16.5
      +/- 8.0 kg) per  lactation. Only one GH1 SNP, GH33, was significantly associated 
      with milk protein yield in the second lactation (allele substitution effect of 
      9.8 +/- 5.0 kg). Several GH1 SNPs were significantly associated with  fertility,
      including GH32, GH35 and GH38 with calving to  third parity (22.4 +/- 11.3 days)
      (GH32 and GH38 only), pregnancy  rate to first service (0.1%) and overall
      pregnancy rate (0.05%). The results of  this study demonstrate the effects of
      variants of the somatotrophic axis on  milk production and fertility traits in
      commercial dairy cattle.

PMID- 21948747
TI  - Variability of red rot-resistant somaclones of sugarcane genotype S97US297
      assessed by RAPD and SSR.
AB  - Sugarcane breeding under climatic conditions of Pakistan  is very difficult due
      to unavailability of viable fuzz (seed). Somaclonal  variation can provide an
      alternative for improvement of existing genotypes. Six  hundred and twenty-seven
      somaclones were developed from sugarcane genotype  S97US297, and protocols for
      callogenesis and organogenesis were developed using  Murashige and Skoog medium.
      Two types of explants, leaf and pith, and two  auxins, 2,4-dichlorophenoxy acetic
      acid and indole-3-acetic acid, were tested  to optimize callogenesis for root
      establishment. Leaves as explants with 3.0  mg/L 2,4-dichlorophenoxy acetic acid
      gave the best results, both for callus  induction and proliferation. Half
      strength Murashige and Skoog medium with 1.5  mg/L indole-3-butyric acid proved
      to be the best for rooting. Red rot-resistant  somaclones of the R(2) generation
      along with the parent were assessed for  genetic variability at the molecular
      level using RAPD and SSR markers.  Polymorphism based on RAPD and SSR was 32 and
      67%, respectively. Polymorphic information  content ranged from 0.06-0.45 for
      RAPD and 0.06-0.47 for SSR. We conclude that  somaclonal variation of sugarcane
      varieties is sufficient to allow selection.

PMID- 21948748
TI  - No evidence for association between DRD3 and COMT with schizophrenia in a Malay
      population.
AB  - Molecular components of the dopamine D3 receptor  (DRD3) may play an important
      role in the pathophysiology of schizophrenia.  Previous studies have demonstrated
      an association between DRD3 Ser9Gly and  cathechol-o-methyltransferase (COMT, SNP
      = rs165656) polymorphisms and  schizophrenia but the results were inconclusive.
      We investigated this apparent  association between Ser9Gly (A/G) polymorphism and
      an intronic SNP (dbSNP or  rs165656) in 261 Malay patients diagnosed with
      schizophrenia and 216 controls,  using PCR-RFLP. The genotype distribution of the
      polymorphism DRD3 Ser9Gly was  in Hardy-Weinberg equilibrium (HWE) for patients
      (P = 0.1251) and out of HWE  for controls (P = 0.0137). However, both healthy
      controls and schizophrenia  patients were out of HWE for the polymorphism COMT
      rs165656. Based on allele  and genotype frequencies in both groups, we found no
      significant association of  DRD3 Ser9Gly polymorphisms and COMT (rs165656) with
      schizophrenia in Malays.  Further studies should examine the association between
      other dopamine-related  genes and the behavioral phenotypes of schizophrenia.

PMID- 21948749
TI  - STAT3 gene polymorphisms and susceptibility to non-small cell lung cancer.
AB  - Signal transducer and activator of transcription  protein 3 (STAT3) has been
      implicated in cancer development and is recognized  as a type of oncogene.
      However, association studies of single nucleotide polymorphisms  (SNPs) in the
      STAT3 gene with cancer risk are rare and not available for  lung cancer. We
      examined whether STAT3 polymorphisms are associated with  the risk of non-small
      cell lung cancer (NSCLC). Eight SNPs in the STAT3 gene  were genotyped by TaqMan
      assays in 326 NSCLC cases and 432 controls in a  Chinese population. Significant
      decreased risk of NSCLC was observed for  carriers of minor alleles rs4796793
      (odds ratio (OR) = 0.68, 95% confidence  interval (CI) = 0.51-0.92), rs7211777
      (OR = 0.67, 95%CI = 0.50-0.90),  rs12949918 (OR = 0.73, 95%CI = 0.54-0.97),
      rs744166 (OR = 0.69, 95%CI =  0.51-0.92), rs9912773 (OR = 0.75, 95%CI = 0.55
      0.98), and rs3869550 (OR = 0.70,  95%CI = 0.53-0.94). The GGCGGC haplotype,
      comprised of minor alleles of the six  NSCLC-associated SNPs, had a 0.78-fold
      (95%CI = 0.62-0.97) significantly  decreased risk of NSCLC, as compared to the
      most common haplotype of CATACT.  Stratification analyses by clinical stage
      showed that the trend for the  association between STAT3 polymorphisms and NSCLC
      risk was present both  for stage I/II and stage III/IV, and appeared moderately
      stronger for stage  III/IV. We conclude that polymorphisms in the STAT3 gene may
      have a  protective role in the development of NSCLC, particular of stage III/IV
      NSCLC.

PMID- 21948750
TI  - Effect of mutations in a simian virus 40 PolyA signal enhancer on green
      fluorescent protein reporter gene expression.
AB  - Our previous studies have shown that tandem Alu repeats  inhibit green
      fluorescent protein (GFP) gene expression when inserted  downstream of the GFP
      gene in the pEGFP-C1 vector. We found that the 22R sequence  (5'
      GTGAAAAAAATGCTTTATTTGT-3') from the antisense PolyA (240 bp polyadenylation 
      signal) of simian virus 40, eliminated repression of GFP gene expression when 
      inserted between the GFP gene and the Alu repeats. The 22R sequence  contains an
      imperfect palindrome; based on RNA structure software prediction,  it forms an
      unstable stem-loop structure, including a loop, a first stem, a  bulge, and a
      second stem. Analysis of mutations of the loop length of the 22R  sequence showed
      that the three-nucleotide loop (wild-type, 22R) induced much  stronger GFP
      expression than did other loop lengths. Two mutations, 4TMI (A7->T,  A17->T) and
      5AMI (A6->T, T18->A), which caused the base type changes in the bulge  and in the
      second stem in the 22R sequence, induced stronger GFP gene  expression than 22R
      itself. Mutation of the bulge base (A17->T), leading to complete  complementation
      of the stem, caused weaker GFP gene expression. Sequences  without a palindrome
      (7pieA, 5'-GTGAAAAAAATG CAAAAAAAGT-3', 7pieT,  5'-GTGTTTTTTTTGCTTTTTTTGT-3') did
      not activate GFP gene expression. We conclude  that an imperfect palindrome
      affects and can increase GFP gene expression.

PMID- 21948751
TI  - Primed in situ labeling for detecting single-copy genes.
AB  - In  order to analyze male sterility caused by deletion of SRY and DAZ, we
      examined  the accuracy and cost-effectiveness of a modified primed in situ
      labeling  (PRINS) technique for detection of single-copy genes. Peripheral blood
      samples  were collected from 50 healthy men; medium-term cultured lymphocytes
      from these  samples were suspended in fixative solution and then spread on clean
      slides. We  used four primers homologous to unique regions of the SRY and DAZ
      regions of  the human Y-chromosome and incorporated reagents to increase
      polymerase  specificity and to enhance the hybridization signal. PRINS of SRY and
      DAZ gave  bands at Yp11.3 and Yq11.2, respectively, in all 50 metaphase spreads.
      The  PRINS SRY signals were as distinct as those obtained using traditional 
      fluorescence in situ hybridization (FISH). This new method is ideal for  rapid
      localization of single-copy genes or small DNA segments, making PRINS a  cost
      effective alternative to FISH. Further enhancement of PRINS to increase  its
      speed of implementation may lead to its wide use in the field of medical 
      genetics.

PMID- 21948752
TI  - Linkage mapping of the Mediterranean cypress, Cupressus sempervirens, based on
      molecular and morphological markers.
AB  - Gene  mapping for a Cupressus species is presented for the first time. Two 
      linkage maps for the Mediterranean cypress (Cupressus sempervirens)  varieties,
      C. sempervirens var. horizontalis and C.  sempervirens var. pyramidalis, were
      constructed following the  pseudo-testcross mapping strategy and employing RAPD,
      SCAR and morphological  markers. A total of 427 loci (425 RAPDs, two SCARs)
      representing parents and F(1) progeny  were screened for polymorphism with 32
      random decamer and two SCAR primers. A  morphological marker defined as "crown
      form" was also included. Of 274  polymorphic loci, the 188 that presented
      Mendelian inheritance formed the  mapping dataset. Of these loci, 30% were mapped
      into seven linkage groups for  the horizontalis (maternal) and four linkage
      groups for the pyramidalis (paternal) map. The putative "crown form" locus was
      included in a linkage  group of both maps. The horizontalis and the pyramidalis
      maps  covered 160.1 and 144.5 cM, respectively, while genome length was estimated
      to  be 1696 cM for the former variety and 1373 cM for the latter. The four RAPD 
      markers most tightly linked to crown form were cloned and converted to SCARs. 
      Each of the cloned RAPD markers yielded two to three different sequences 
      behaving as co-migrating fragments. Two SCAR markers, SC-D05(432) and  SC
      D09(667), produced amplified bands of the expected sizes and  maintained linkage
      with the appropriate phenotype, but to a lesser extent  compared to their
      original RAPD counterparts. These linkage maps represent a  first step towards
      the localization of QTLs and genes controlling crown form  and other polygenic
      traits in cypress.

PMID- 21948753
TI  - Genetic status of the wood stork (Mycteria americana) from the southeastern
      United States and the Brazilian Pantanal as revealed by mitochondrial DNA
      analysis.
AB  - The  wood stork (Mycteria americana) is a colonial wading bird that inhabits  the
      Neotropical region from the southeastern United States (US) to northern 
      Argentina. The species is considered to be endangered in the US due to 
      degradation of its foraging and breeding habitat. In other parts of its range, 
      such as in the Brazilian Pantanal region, breeding populations of this species 
      appear to be stable. We compared the levels of genetic variability and 
      population structuring of the US and the Pantanal breeding populations using 
      mitochondrial DNA (mtDNA) control region sequences. Twenty-seven haplotypes  were
      identified among 88 wood stork samples collected from eight breeding  colonies in
      the US and eight in the Pantanal. Patterns indicative of  heteroplasmy were
      observed in 35.3% of the mtDNA sequences that were examined.  Significantly
      higher levels of haplotype diversity were observed in the  Pantanal samples
      compared to those from the US, suggesting that during the  last century,
      demographic declines or a recent evolutionary bottleneck reduced  the levels of
      mtDNA variability of the US population. Analyses of genetic  structuring revealed
      non-significant genetic differentiation between these  regions, indicating that
      either the populations were only recently separated or  that gene flow continues
      to occur at low levels. Haplotype network analysis  indicated low current levels
      of gene flow between populations that were closely  related in the past.

PMID- 21948754
TI  - Short aggrecan gene repetitive alleles associated with lumbar degenerative disc
      disease in Turkish patients.
AB  - We  investigated a possible association between aggrecan gene polymorphism  and
      lumbar degenerative disc disease in Turkish patients. One hundred  20-30-year-old
      patients with or without low back pain were selected for the  study. Lumbar
      magnetic resonance imaging was performed on all patients. The  patient group had
      low back pain clinically and degenerative disc disease  radiographically. The
      control group included patients with and without low back  pain: all were
      negative radiographically for degenerative disc disease. Genomic  DNA was
      extracted from all participants. A PCR assay were used to evaluate  variable
      number of tandem repeat polymorphism of aggrecan gene alleles  to determine if
      there was any correlation with degenerative disc disease.  Significant
      associations were found between short repeated alleles of the aggrecan gene and
      severe disc degeneration. A significant association was also found  between short
      repeated alleles of the aggrecan gene and multilevel disc  herniation as well as
      extrusion and sequestration types of disc herniation. In  Turkish population,
      short repeated alleles of the aggrecan gene are  associated with increased disc
      degeneration and disc herniation.

PMID- 21948755
TI  - Functional analysis of the cellulose gene of the pine wood nematode,
      Bursaphelenchus xylophilus, using RNA interference.
AB  - Cellulases  are pathogenic substances suspected to be responsible for the
      development of  the early symptoms of nematode disease. The pine wood nematode,
      Bursaphelenchus  xylophilus (Parasitaphelenchidae), is the causal agent of pine
      wilt  disease, which kills millions of pine trees. We used RNA interference
      (RNAi), a  reverse genetic tool, to analyze the function of the endo-beta-1,4
      glucanase gene of B.  xylophilus, which causes the most serious forest tree
      disease in China and  the rest of eastern Asia. Silencing of this gene was
      detected through real-time  PCR and cellulase activity assays after soaking for
      24 h in dsRNA. The  cellulase gene silencing effects differed among various
      siRNAs. The propagation  and dispersal ability of these nematodes decreased when
      the endo-beta-1,4-glucanase gene was silenced.  It is important to select an
      effective siRNA before performing an RNAi test.

PMID- 21948756
TI  - Relationship between the magnitude of the inbreeding coefficient and milk traits
      in Holstein and Jersey dairy bull semen used in Brazil.
AB  - Artificial  insemination has been used to improve production in Brazilian dairy
      cattle;  however, this can lead to problems due to increased inbreeding. To
      evaluate the  effect of the magnitude of inbreeding coefficients on predicted
      transmitting  abilities (PTAs) for milk traits of Holstein and Jersey breeds,
      data on 392  Holstein and 92 Jersey sires used in Brazil were tabulated. The
      second-degree  polynomial equations and points of maximum or minimal response
      were estimated  to establish the regression equation of the variables as a
      function of the  inbreeding coefficients. The mean inbreeding coefficient of the
      Holstein bulls  was 5.10%; this did not significantly affect the PTA for percent
      milk fat,  protein percentage and protein (P = 0.479, 0.058 and 0.087,
      respectively).  However, the PTAs for milk yield and fat decreased significantly
      after  reaching inbreeding coefficients of 6.43 (P = 0.034) and 5.75 (P = 0.007),
      respectively. The mean inbreeding coefficient of Jersey bulls was 6.45%; the 
      PTAs for milk yield, fat and protein, in pounds, decreased significantly after 
      reaching inbreeding coefficients of 15.04, 9.83 and 12.82% (P < 0.001, P = 
      0.002, and P = 0.001, respectively). The linear regression was only significant 
      for fat and protein percentages in the Jersey breed (P = 0.002 and P = 0.005, 
      respectively). The PTAs of Holstein sires were more affected by smaller 
      magnitudes of inbreeding coefficients than those of Jersey sires. It is 
      necessary to monitor the inbreeding coefficients of sires used for artificial 
      insemination in breeding schemes in Brazil, since the low genetic variability  of
      the available sires may lead to reduced production.

PMID- 21948757
TI  - Molecular characterization, polymorphism of the ACOX1 gene and association with
      ultrasound traits in Bos taurus.
AB  - Acyl-coenzyme  A oxidase 1 (ACOX1) is the first enzyme in peroxisomal fatty acid
      beta-oxidation;  it is rate-limiting and plays a key role in fatty acid
      metabolism and fat  deposition. ACOX1 is an important candidate gene for meat
      quality selection  through marker-assisted selection. Genomic structural analysis
      showed that  bovine ACOX1 shares 86% identity with human ACOX1. Using PCR-SSCP
      technology,  we discovered a single nucleotide polymorphism (SNP) (A1865C) in
      exon 13 of the  ACOX1 gene. Allele frequencies of this SNP were investigated and
      evaluated with  the chi(2) test in 641 cattle  populations; only the Jiaxian red
      population was not in Hardy-Weinberg  equilibrium. Gene heterozygosity, effective
      allele numbers and polymorphism  information content of the bovine ACOX1 locus in
      seven populations varied from  0.2778 to 0.4954, 1.3846 to 1.9817 and 0.2392 to
      0.3727, respectively. We also  looked for a potential association of this SNP
      with ultrasound traits in 327  individuals and found a significant effect on
      ultrasound backfat thickness and  ultrasound marbling score (P < 0.05). Meat
      quality traits were analyzed in  another 71 Qinchuan individuals to determine
      associations with genotype. Animals  with genotype AA had higher mean values of
      backfat thickness than those with  genotypes AC and CC. A represents the base
      before mutation and C represents the  base after mutation. We conclude that this
      SNP of the ACOX1 gene has potential  as a genetic marker for meat quality traits
      in cattle reproduction and breeding.

PMID- 21948758
TI  - ms17: a meiotic mutation causing partial male sterility in a corn silage hybrid.
AB  - Cytological analysis under light microscopy of the  single hybrid P30R50 of
      silage corn revealed an abnormal pattern of  microsporogenesis that affected the
      meiotic products. Meiosis progressed  normally until diakinesis, but before
      migration to the metaphase plate,  bivalents underwent total desynapsis and 20
      univalent chromosomes were  scattered in the cytoplasm. At this stage, meiocytes
      also exhibited a number of  chromatin-like fragments scattered throughout the
      cell. Metaphase I was  completely abnormal in the affected cells, and univalent
      chromosomes and  fragments were distributed among several curved spindles.
      Anaphase I did not  occur, and each chromosome or group of chromosomes originated
      a micronucleus.  After this phase, an irregular cytokinesis occurred, and
      secondary meiocytes  with several micronuclei were observed. Metaphase II and
      anaphase II also did  not occur, and after the second cytokinesis, the genomes
      were fractionated into  polyads, generating several unbalanced microspores, with
      various-sized nuclei.  About 35% of the tetrads were abnormal in the hybrid. This
      spontaneous mutation  had been previously reported in a USA maize line called
      ms17 and was  found to cause male sterility.

PMID- 21948759
TI  - cDNA cloning and mRNA expression of a tandem-repeat galectin (PoGal2) from the
      pearl oyster, Pinctada fucata.
AB  - Galectins can recognize and specifically bind to beta-galactoside residues,
      playing crucial roles in innate immune responses of vertebrates and
      invertebrates. We cloned the cDNA of a tandem-repeat galectin from the pearl
      oyster Pinctada fucata (designated as PoGal2). PoGal2 cDNA is 1347 bp long and
      consists of a 5'-untranslated region (UTR) of 3 bp, a 3'-UTR of 297 bp with one
      cytokine RNA instability motif (ATTTA), and an open reading frame of 1047 bp,
      encoding a polypeptide of 349 amino acids, with an estimated molecular mass of
      38.1 kDa and a theoretical isoelectric point of 8.5. PoGal2 contains two
      carbohydrate recognition domains (CRDs); both have the conserved carbohydrate
      binding motifs H-NPR and WG-EE. PoGal2 shares 50.6 and 50.9% identity with those
      of abalone (Haliotis discus) and the Manila clam (Venerupis philippinarum),
      respectively. Phylogenetic analysis revealed that the tandem-repeat galectins
      formed two clades for the different species. Molluscan tandem-repeat galectins
      were clustered into a single clade, and nematode tandem-repeat galectins were
      clustered into another single clade. In both clades, CRD-N and CRD-C were divided
      into different groups. PoGal2 mRNA was constitutively expressed in all tissues
      analyzed, and the expression level of PoGal2 mRNA was found to be significantly
      up-regulated in digestive glands, gills and hemocytes after Vibrio alginolyticus
      stimulation/infection. Expression profile analysis showed that the expression
      level of PoGal2 mRNA was significantly up-regulated at 8, 12 and 24 h after V.
      alginolyticus infection. These results suggest that PoGal2 is a constitutive and
      inducible acute-phase protein involved in the innate immune response of pearl
      oysters.

PMID- 21948760
TI  - Apolipoprotein E polymorphism in elderly Japanese-Brazilian immigrants does not
      explain the reduced cardiovascular risk factor incidence.
AB  - Study of immigrant populations may contribute to a  better understanding of the
      epidemiology of diseases associated with the aging process.  We examined the
      prevalence of cardiovascular risk factors, including  apolipoprotein E (ApoE)
      polymorphism, in elderly subjects who were born in  Japan, migrated to South
      Brazil and have lived in that region for over 40  years, versus a group of
      elderly, locally born Brazilians living in the same  region. These Japanese
      subjects came to Brazil after World War II (1950-1960)  from several Japanese
      cities, mainly Nagasaki, Kumamoto and Hokkaido. Among  1007 subjects genotyped
      for ApoE polymorphism, we selected 540 elderly subjects  (>60 years old),
      consisting of 270 Japanese-Brazilians and 270 Brazilians of  European ancestry
      from Rio Grande do Sul State (Gaucha population). The  Japanese-Brazilian group
      had significantly lower prevalences of obesity, type 2  diabetes mellitus,
      dyslipidemia, and metabolic syndrome than did the Gaucho  population group. ApoE
      polymorphism frequencies were similar in the two groups.  The differences in
      cardiovascular risk factors observed in the two populations  cannot be explained
      by ApoE polymorphism; they could be related to conservation  of Japanese
      lifestyle habits, such as diet.

PMID- 21948761
TI  - Novel representation of RNA secondary structure used to improve prediction
      algorithms.
AB  - We propose a novel representation of RNA secondary  structure for a quick
      comparison of different structures. Secondary structure  was viewed as a set of
      stems and each stem was represented by two values  according to its position.
      Using this representation, we improved the  comparative sequence analysis method
      results and the minimum free-energy model.  In the comparative sequence analysis
      method, a novel algorithm independent of  multiple sequence alignment was
      developed to improve performance. When dealing  with a single-RNA sequence, the
      minimum free-energy model is improved by  combining it with RNA class
      information. Secondary structure prediction  experiments were done on tRNA and
      RNAse P RNA; sensitivity and specificity were  both improved. Furthermore,
      software programs were developed for non-commercial  use.

PMID- 21948762
TI  - Association of serum sex steroid levels and bone mineral density with CYP17 and
      CYP19 gene polymorphisms in postmenopausal women in Turkey.
AB  - Many clinical conditions, including osteoporosis, are  associated with serum
      levels of sex steroids. Enzymes that regulate  rate-limiting steps of
      steroidogenic pathways, such as CYP17 and CYP19, are  also regarded as
      significant factors that may cause the development of these  conditions. We
      investigated the association of two common polymorphisms, in the  promoter region
      (T->C substitution) of CYP17 and exon 3 (G->A) of CYP19, with  bone mineral
      density (BMD) in the lumbar spine and femoral neck and serum  androgen/estradiol,
      in a case-control study of 172 postmenopausal women aged  62.3 +/- 9.6 years
      (mean +/- SD). The CYP17 TC genotype was significantly  overrepresented in
      patients compared to controls, and TC genotype neck T-score  and lumbar T-score
      values were significantly higher in patients compared to  controls. CYP17 TC and
      TT genotype testosterone and DHEA-SO(4) levels were lower in patients compared to
      controls.  All three genotypes of CYP19 had almost the same distribution among
      patients.  The CYP19 AG genotype, however, was most frequent among controls.
      CYP19 lumbar  BMD levels were close to each other among the different genotypes;
      however, AA  and AG genotypes were significantly lower in patients. Testosterone
      and DHEA-SO(4) levels in the CYP19 GG genotype were higher compared  to those of
      the other genotypes in patients but not in controls. CYP19 GA  individuals had
      lower E(2) levels  and lower BMD in controls and patients. Femoral neck BMD and
      lumbar T-score  were also diminished with GA transition. In conclusion, CYP17 and
      CYP19 gene  polymorphisms were found to be associated with osteoporosis in
      postmenopausal  women in Turkey.

PMID- 21948763
TI  - Effects of intra- and  extracellular factors on anti-aging klotho gene
      expression.
AB  - Inactivation  of the klotho gene in mice causes serious systemic disorders,
      resembling  human aging. However, at the molecular level, its action mechanisms
      are not  well understood. The stimulatory or inhibitory effects of cis- and 
      trans-regulatory factors on the klotho gene expression are also still  unclear.
      We studied the effects of intra- and extracellular factors on human klotho gene
      expression. For this purpose, pHKP-Luc and pHKP-GFP reporter vectors  were
      constructed with the 2.1-kbp upstream region of human klotho,  covering its
      promoter region, using luciferase and GFP genes as the reporter. A  series of
      vectors that have deletions in the upstream region of the klotho gene  were
      constructed to assay cis-acting factors. Deletion of some parts of the klotho
      gene upstream region significantly affected reporter gene expression in  HEK293
      cells. p16 and p53 proteins inhibited reporter luciferase expression  under the
      control of human klotho promoter in a dose-dependent manner.  Calcium and
      phosphate ions stimulated klotho expression. p21, PTH,  IGF-1, and angiotensin-II
      had no significant effect on klotho expression  in HEK293 cells.

PMID- 21948764
TI  - Characterization of chloroplast DNA microsatellites from Saccharum spp and
      related species.
AB  - Microsatellites,  or simple sequence repeats (SSRs), and their flanking regions
      in chloroplast  genomes (plastomes) of some species of the family Poaceae were
      analyzed in  silico to look for DNA sequence variations. Comparison of the
      complete  chloroplast DNA sequences (cpDNAs) of sugarcane (Saccharum hybrid cv. 
      SP-80-3280 and S. officinarum cv. NCo310) and related species, Agrostis 
      stolonifera, Brachypodium distachyon, Hordeum vulgare subsp vulgare, Lolium
      perenne, Oryza nivara, O. sativa subsp indica, O. sativa subsp japonica, Sorghum
      bicolor, Triticum  aestivum, Zea mays, and Z. mays cv. B73, allowed us to 
      examine the organization of chloroplast SSRs (cpSSRs) in genic and intergenic 
      regions. We identified 204 cpSSRs in the sugarcane cpDNA; 22.5% were in genic 
      regions. The ndh, rps, trn, and rpl gene clusters  of the chloroplasts had the
      most repeats. Mononucleotide repeats were the most  abundant cpSSRs in these
      species; however, di-, tri-, tetra-, penta-, and  hexanucleotide repeats were
      also identified. Many base substitutions and  deletions/insertions were
      identified in the cpSSR loci and their flanking  regions. Multiple alignments of
      all cpSSR sequences of Poaceae species made  identification of nucleotide
      variability possible; repeat motifs are not  uniformly distributed across the
      Poaceae plastomes, but are mostly confined to  intergenic regions. Phylogeny was
      determined by maximum parsimony and  neighbor-joining inference methods. The
      cpSSRs of these species were found to  be polymorphic. It appears that individual
      cpSSRs in the Poaceae are stable, at  least over short periods of evolutionary
      time. We conclude that the plastome  database can be exploited for phylogenetic
      analysis and biotechnological  development.

PMID- 21948765
TI  - Isolation and characterization of tetranucleotide repeat polymorphic
      microsatellite loci in Larus saundersi (Aves, Laridae).
AB  - Nine polymorphic microsatellite loci were isolated, using  tetranucleotide repeat
      oligonucleotide probes from an enriched DNA library of  the globally "vulnerable"
      Saunders's gull (Larus saundersi), collected  from the Yancheng coastal wetland,
      one of the three remaining breeding sites in  China. Six breast muscle tissues
      and 16 blood samples from 22 gulls and eight  eggshell membrane tissues were
      collected for this analysis. The number of  alleles per locus ranged from 4 to
      15, with a mean of 8.9. The observed and  expected heterozygosities ranged from
      0.58 to 0.89 and 0.58 to 0.9, with means  of 0.77 and 0.81, respectively. No
      significant linkage disequilibrium and no  divergence from Hardy-Weinberg
      equilibrium were detected among these loci.  Based on Micro-Checker tests, no
      null alleles are present at any of the loci.  The microsatellite loci described
      here will be valuable for exploring  population genetic structure and for other
      relevant genetic studies of  Saunders's gull.

PMID- 21948766
TI  - DNA-programmed Glaser-Eglinton reactions for the synthesis of conjugated
      molecular wires.

PMID- 21948767
TI  - Synergistic effect of resveratrol and quercetin released from drug-eluting
      polymer coatings for endovascular devices.
AB  - This study describes the development and evaluation of novel polymer films that
      provide controlled release of two vascular-protective polyphenols for
      endovascular devices. Resveratrol (RESV) and quercetin (QUER) have antimigratory
      and antiproliferative actions on vascular smooth muscle cells (VSMCs), inhibit
      both platelet and inflammatory cell activation, and promote endothelial cell
      function. Our aim is to develop and characterize coatings that release these
      drugs within a therapeutic range. The most synergistic drug combination, as
      determined by isobolographic analysis, was incorporated into an arborescent
      poly(styrene-isobutylene-styrene) tri-block polymer (arbIBS) and applied to
      stainless steel coupons using an electrospray process. Physical characterization
      of the resulting coating revealed a film featuring micro-scale architecture
      consisting of drug-containing domains. To determine drug-mediated effects,
      vascular cells were exposed to coatings incorporating several loadings of RESV
      and QUER. Results from this study indicate that arbIBS exhibits no cytotoxicity,
      and that the films release RESV and QUER at therapeutic levels, dose-dependently
      inhibiting macrophage activation, VSMC proliferation, and platelet stimulation.
      We conclude that RESV and QUER released from arbIBS interfere with key processes
      responsible for in-stent stenosis, suggesting that RESV and QUER may have utility
      as therapeutics in a novel coating for device-based interventions.

PMID- 21948768
TI  - Biobehavioral aspects of health and aging among people of Mexican origin.
AB  - There is a growing interest in developing a deeper level of understanding of the
      complex phenomena that make up the aging process. Efforts to pursue questions
      using a multivariate and ecologically valid approaches that include biological
      and behavioral factors have led to significant advances in our knowledge. This
      special issue presents a collection of papers that represent this "biobehavioral"
      perspective. Little is known concerning the biobehavioral aspects of Hispanic
      health and there is a dearth of systematic study of how individual biological
      factors interact with the environmental and cultural factors to affect health
      outcomes among the swiftly growing older population of Mexican origin, a subgroup
      of older minorities that exhibits unique morbidity and mortality patterns. The
      group of papers here represents important contributions to understanding the
      health consequences in later life for individuals of Mexican descent and
      addresses several areas of interest including but not limited to diabetes,
      cognitive impairment, metabolic syndrome, frailty, socio-economic status and
      contextual factors that impact health. The papers presented here use interesting
      and useful transdisciplinary approaches that increase our knowledge of health
      processes in older people of Mexican descent. This special issue also provides
      excellent examples of the critical linkages between biological variables broadly
      defined and traditional social stratification, social inequalities, and social
      justice and the ways in which they interact. The papers taken together suggest
      that the processes involved in aging and health are complex, particularly in
      people of Mexican descent, and requires the understanding of mechanisms at
      multiple causes and levels of analysis.

PMID- 21948769
TI  - Life-course exposure to early socioeconomic environment, education in relation to
      late-life cognitive function among older Mexicans and Mexican Americans.
AB  - OBJECTIVES: To examine the associations between life-course education and late
      life cognitive function along with the modifying role of migration history.
      METHOD: The combined sample includes 1,789 participants from the Sacramento Area
      Latino Study on Aging and 5,253 participants from the Mexican Health and Aging
      Study. Aged 60+ at baseline, participants were classified as Mexican residents,
      Mexicans-return migrants, Mexicans-immigrants to the United States, and Mexicans
      U.S. born. Cognitive function was measured using standardized z scores of a short
      term verbal recall test. Multivariate linear regression analysis was conducted.
      RESULTS: Participants' z scores were higher among those whose mother had more
      than elementary education (beta = 0.28, p < .05). Participant's education
      mediated this association. For 5-year difference in education, the cognitive z
      score increased by 0.3 points for a U.S. born. Results were similar with father's
      education. DISCUSSION: Adult educational attainment mediates the effect of
      childhood socioeconomic status on late-life cognition. Migration plays a role in
      shaping cognitive aging.

PMID- 21948770
TI  - Prevalence and incidence rates of dementia and cognitive impairment no dementia
      in the Mexican population: data from the Mexican Health and Aging Study.
AB  - OBJECTIVE: To estimate the prevalence and incidence of dementia and cognitive
      impairment without dementia (CIND) in the Mexican population. METHOD: The MHAS
      study is a prospective panel study of health and aging in Mexico with 7,000
      elders that represent eight million participants nationally. Using measurements
      of cognition and activities of daily living of dementia cases and CIND were
      identified at baseline and follow-up. Overall incidence rates and specific rates
      for sex, age, and education were calculated. RESULTS: Prevalence was 6.1% and
      28.7% for dementia and CIND, respectively. Incidence rates were 27.3 per 1,000
      person-years for dementia and 223 per 1,000 persons-year for CIND. Rates of
      dementia and CIND increased with advancing age and decreased with higher
      educational level; sex had a differential effect depending on the age strata.
      Hypertension, diabetes, and depression were risk factors for dementia but not for
      CIND. DISCUSSION: These data provide estimates of prevalence and incidence of
      dementia and cognitive impairment in the Mexican population for projection of
      future burden.

PMID- 21948771
TI  - The provision of diabetes-monitoring exams to older Latinos.
AB  - OBJECTIVES: To explore factors associated with the provision of diabetes
      monitoring practices among older Latinos with type 2 diabetes. METHOD: Data from
      547 Latinos (>= 55 years) were analyzed from the 2007 California Health Interview
      Survey. Multivariate logistic regression modeled the relationship between health
      status and sociodemographic factors and the receipt of semiannual HbA1c tests,
      annual foot exams, and annual retinal exams. RESULTS: The majority of older
      Latino diabetics received foot exams (87%) and retinal exams (77%), but the
      provision of semiannual HbA1c tests (30%) was low. Higher English-language
      proficiency and health insurance coverage were associated with the provision of
      HbA1c tests and foot exams, but not retinal exams. Insulin therapy was positively
      associated with semiannual HbA1c testing, but negatively associated with foot
      exams. DISCUSSION: There are considerable missed opportunities in the provision
      of diabetes monitoring for older Latinos, particularly those with limited English
      proficiency, less comprehensive insurance, and noninsulin therapy.

PMID- 21948772
TI  - The metabolic syndrome, biomarkers, and the acculturation-health relationship
      among older Mexican Americans.
AB  - OBJECTIVE: To examine the acculturation-health relationship using metabolic
      syndrome biomarkers. METHOD: Cross-sectional sample data. PARTICIPANTS: 1,789
      Mexican Americans (60 years and older) from northern California. MAIN OUTCOME:
      Biomarkers (waist circumference, blood pressure, fasting plasma glucose,
      triglycerides, and high-density lipids) were used to construct the metabolic
      syndrome indicator using American Heart Association criteria. MAIN PREDICTOR:
      Acculturation Rating Scale for Mexican Americans-II scores. RESULTS: Higher
      acculturation scores were associated with a significantly lower risk for the
      metabolic syndrome for foreign-born, but not U.S.-born, Mexican Americans.
      CONCLUSION: Immigrant health advantages over U.S.-born Mexican Americans are not
      evident in older adulthood. Higher acculturation was associated with lowered
      metabolic syndrome risk among older foreign-born Mexican Americans. This suggests
      that the prevailing acculturative stress hypothesis may not apply to the health
      of older adults and that any negative relationship between acculturation and
      health found in younger adults may yield to different developmental health
      influences in later adulthood.

PMID- 21948773
TI  - Links between childhood and adult social circumstances and obesity and
      hypertension in the Mexican population.
AB  - OBJECTIVES: This study examines links between early life circumstances and adult
      socioeconomic status and obesity and hypertension in the adult Mexican
      population. METHOD: We use data from the Mexican Family Life Survey (MxFLS)
      collected in 2002 for people aged 20 or older (N = 14,280). RESULTS: We found
      that men with low education and women with more education have significantly
      lower obesity. Women with higher education also have significantly less
      hypertension. Obesity triples the likelihood of hypertension among both men and
      women. Better childhood experiences are associated with less hypertension among
      women, but more hypertension among men in rural areas. DISCUSSION: Recent changes
      in income, nutrition, and infection in Mexico may be responsible for the observed
      high prevalence of overweight and obesity and the extremely high odds of
      hypertension among obese young adults.

PMID- 21948775
TI  - Ndel1, Nudel (Noodle): flexible in the cell?
AB  - Nuclear distribution element-like 1 (Ndel1 or Nudel) was firstly described as a
      regulator of the cytoskeleton in microtubule and intermediate filament dynamics
      and microtubule-based transport. Emerging evidence indicates that Ndel1 also
      serves as a docking platform for signaling proteins and modulates enzymatic
      activities (kinase, ATPase, oligopeptidase, GTPase). Through these structural and
      signaling functions, Ndel1 plays a role in diverse cellular processes (e.g.,
      mitosis, neurogenesis, neurite outgrowth, and neuronal migration). Furthermore,
      Ndel1 is linked to the etiology of various mental illnesses and neurodegenerative
      disorders. In the present review, we summarize the physiological and pathological
      functions associated with Ndel1. We further advance the concept that Ndel1
      interfaces GTPases-mediated processes (endocytosis, vesicles
      morphogenesis/signaling) and cytoskeletal dynamics to impact cell signaling and
      behaviors. This putative mechanism may affect cellular functionalities and may
      contribute to shed light into the causes of devastating human diseases.

PMID- 21948776
TI  - Compression-compression fatigue of selective electron beam melted cellular
      titanium (Ti-6Al-4V).
AB  - Regular 3D periodic porous Ti-6Al-4V structures intended to reduce the effects of
      stress shielding in load-bearing bone replacement implants (e.g., hip stems) were
      fabricated over a range of relative densities (0.17-0.40) and pore sizes
      (approximately 500-1500 MUm) using selective electron beam melting (EBM).
      Compression-compression fatigue testing (15 Hz, R = 0.1) resulted in normalized
      fatigue strengths at 10(6) cycles ranging from 0.15 to 0.25, which is lower than
      the expected value of 0.4 for solid material of the same acicular alpha
      microstructure. The three possible reasons for this reduced fatigue lifetime are
      stress concentrations from closed porosity observed within struts, stress
      concentrations from observed strut surface features (sintered particles and
      texture lines), and microstructure (either acicular alpha or martensite) with
      less than optimal high-cycle fatigue resistance.

PMID- 21948774
TI  - The protective effect of neighborhood composition on increasing frailty among
      older Mexican Americans: a barrio advantage?
AB  - OBJECTIVE: Little is known about the nature of the frailty syndrome in older
      Hispanics who are projected to be the largest minority older population by 2050.
      The authors examine prospectively the relationship between medical, psychosocial,
      and neighborhood factors and increasing frailty in a community-dwelling sample of
      Mexican Americans older than 75 years. METHOD: Based on a modified version of the
      Cardiovascular Health Study Frailty Index, the authors examine 2-year follow-up
      data from the Hispanic Established Populations for Epidemiologic Studies of the
      Elderly (H-EPESE) to ascertain the rates and determinants of increasing frailty
      among 2,069 Mexican American adults 75+ years of age at baseline. RESULTS:
      Respondents at risk of increasing frailty live in a less ethnically dense Mexican
      American neighborhood, are older, do not have private insurance or Medicare, have
      higher levels of medical conditions, have lower levels of cognitive functioning,
      and report less positive affect. DISCUSSION: Personal as well as neighborhood
      characteristics confer protective effects on individual health in this
      representative, well-characterized sample of older Mexican Americans. Potential
      mechanisms that may be implicated in the protective effect of ethnically
      homogenous communities are discussed.

PMID- 21948777
TI  - Varicose veins: a critical review of the definition and the therapeutical
      options.
AB  - This review intends to give an overview of the present therapeutic options for
      varicose vein disease. The definition of varicose vein disease and its recurrence
      are made and discussed with new aspects including duplexsonography assessment.
      All therapeutic approaches have developed and refined their treatment modalities,
      the open surgical as well as the endovenous techniques. In particular the ?new?
      endovenous techniques are described with regard to safety and outcome, the
      published literature in this respect is summarized. The studies comparing the
      different techniques are listed, the prospective long term studies comparing the
      new techniques with the so called gold standard (open surgery) shall decide on
      the fate of the different techniques.

PMID- 21948778
TI  - Results of open vascular surgical therapy in chronic peripheral arterial disease.
AB  - Surgery in chronic peripheral arterial disease (PAD) can alleviate symptoms in
      claudicants and may impede amputation in critical limb ischemia. The current data
      on different surgical strategies and techniques from the aortoiliac region to the
      pedal arteries as well as amputation as last resort are described and discussed.
      Treatment of PAD depends on the condition of the patient and his comorbidities.
      The question of optimal therapy for each patient cannot always be answered in the
      operating theatre or the angio-suite.

PMID- 21948779
TI  - Transforming growth factor-beta signaling pathway in Marfan's syndrome: a
      preliminary histopathological study.
AB  - BACKGROUND: Marfan's syndrome is an inherited disorder that affects the
      connective tissue. It has been proposed that mutations of FBN1 gene or of
      transforming growth factor (TGF)-beta type II receptor may be responsible for its
      pathogenesis. However, the role of TGF-beta signaling pathway in the development
      of Marfan's syndrome has not been comprehensively investigated. MATERIALS AND
      METHODS: Surgical specimens of the aorta were obtained from two female Marfan
      patients, and the control aortic tissue was taken from an autopsy of a healthy
      individual. The aortic specimens were examined with hematoxylin-eosin, Masson's
      trichrome, von Gieson/victoria blue-van Gieson bichrome, and immunohistochemical
      stainings of TGF-beta1, TGF-beta type I receptor, Smad2/3, Smad4 and Smad7.
      RESULTS: Hematoxylin-eosin staining demonstrated severe elastic lamellar
      disruption and patchy vascular smooth muscle dissolution in the aortic media of
      the Marfan patients. Collagen deposition, interlamilar elastic fiber
      fragmentation, loss or proliferation, and acid mucopolysaccharide accumulation
      were observed in the disarrayed aortic wall structures of Marfan patients by
      Masson's trichrome, victoria blue-van Gieson bichrome, and Alcian blue and
      periodic schiff's (AB-PAS) stainings, respectively. By immunohistochemistry,
      structural disruptions with enhanced TGF-beta;1 in the cytoplasm, Smad2/3 in the
      interstices, Smad4 in the cytoplasm, nuclei or interstices, and OOO Smad7, in the
      nucleus along with attenuated TGF-beta type I receptor in the aortic tissues of
      Marfan patients in comparison to the healthy control. CONCLUSIONS: Marfan
      patients may have aberrant TGF-beta signaling pathway associated with increased
      collagen deposition, interlamilar elastic fiber degenerative changes, and acid
      mucopolysaccharide accumulation. The signaling dysregulation may play an
      important role in the pathogenesis of this genetic disorder.

PMID- 21948780
TI  - Three dimensional rotational angiography in surgical planning of aneurysm
      clipping.
AB  - BACKGROUND: Three-dimensional (3D) angiography is increasingly used in the
      diagnostics of brain aneurysms. Aim of the present study was to evaluate the
      accuracy of 3D angiograms with respect to its value for preoperative planning of
      aneurysm clipping. PATIENTS AND METHODS: The 3D angiograms of 42 patients with
      subarachnoid bleeding caused by aneurysm rupture of the anterior circle of Willis
      and the intradural carotid have been compared to intraoperative photographs of
      the aneurysms. RESULTS: Neighbouring vessels, aneurysm anatomy, arteries
      originating from the aneurysm wall were accurately shown decreasing the surgical
      risk of aneurysm clipping. CONCLUSIONS: The 3D images enabled a perfect
      preoperative planning through the operation by illuminating the aneurysm anatomy,
      neck localisation and shape and relation of the aneurysm to neighbouring vessels.
      Operative approach, use of an accurate clip and avoidance of clipping arteries
      close to the aneurysm have become predictable and safer by the use of 3D
      angiography.

PMID- 21948781
TI  - Diet and the content of selenium and lead in patients with abdominal aortic
      aneurysm.
AB  - BACKGROUND: To evaluate the content of selenium (Se) and lead (Pb) and the
      influence of dietary habits and smoking in patients with abdominal aortic
      aneurysm (AAA). PATIENTS AND METHODS: Forty-nine patients with AAA prior to
      surgical procedures aged 42 - 81 years and a control group of 22 healthy
      volunteers aged 31 - 72 years and 17 aortic wall samples from deceased were
      included in the study. Food-frequency questionnaires were implemented in AAA
      patients to collect the dietary data. Se and Pb concentrations in the serum and
      blood, respectively, and in arterial wall and parietal thrombus samples were
      determined by the atomic absorption spectrometry method. RESULTS: The mean Se
      level in serum of patients with AAA (60.37 +/- 21.2 cm/L) was significantly (p <
      0.008) lower than in healthy volunteers (75.87 +/- 22.4 cm/L). We observed a
      significant correlation (r = 0.69, p < 0.0001) between the content of Se in serum
      and the parietal thrombus of examined patients. Se concentration in aortic wall
      was inversely correlated to the concentration of Pb (r = - 0.38, p < 0.02). We
      observed significantly lower (p < 0.05) concentrations of Se (39.14 +/- 37.1
      cm/g) and significantly higher (p < 0.05) concentrations of Pb (202.69 +/- 180.6
      cm/g) in aortic wall samples of smoking patients than in non-smoking patients
      (77.56 +/- 70.0 cm/g, 73.09 +/- 49.8 cm/g; respectively). CONCLUSIONS: Se serum
      level is lower in patients with AAA than in healthy volunteers. In aortic wall,
      Se concentration is inversely correlated with Pb concentration. Dietary habits
      and smoking have an influence on the Se and Pb status in patients with AAA.

PMID- 21948782
TI  - Effects of walking and strength training on resting and exercise cardiovascular
      responses in patients with intermittent claudication.
AB  - BACKGROUND: Exercise training is recommended as the first-line therapy for
      intermittent claudication patients. However, the effects of exercise therapy on
      cardiovascular function of these patients have been poorly studied. The aim of
      this study is to compare the effects of walking and strength training on
      cardiovascular responses assessed at rest and during exercise in patients with
      intermittent claudication. PATIENTS AND METHODS: Thirty-four patients with stable
      symptoms of intermittent claudication were randomized into two groups: strength
      training (ST) consisting of eight exercises, three sets of 10 repetitions,
      intensity of 11 - 13 on 15-grade Borg scale, 2-min interval between sets; and
      walking training (WT) consisting of walking on a treadmill, 15 bouts of 2-min,
      intensity of 11 - 13 on 15-grade Borg scale, with a 2-min interval between bouts.
      Before and after 12 weeks, blood pressure, heart rate and rate pressure product
      were measured at rest and during a progressive treadmill test until maximal
      claudication pain. RESULTS: Fifteen patients in each group completed the training
      program. After the training programs, resting systolic blood pressure (ST:-6 +/-
      13 mmHg and WT:-3 +/- 18 mmHg, P = .04), heart rate (ST: -6 +/- 10 bpm and WT:-2
      +/- 9 bpm, P = .03), and rate pressure product (ST:-1485 +/- 1442 mmHg*bpm and
      WT:- 605 +/- 2145 mmHg*bpm, P = .01) decreased significantly and similarly in
      both groups. Submaximal systolic blood pressure (ST: -14 +/- 23 mmHg and WT:-6 +/
      23 mmHg, P = .02), and rate pressure product (ST:-1579 +/- 3444 mmHg*bpm and WT:
      -1264 +/- 3005 mmHg*bpm, P = .04) decreased significantly and similarly in both
      groups. There were no changes in submaximal heart rate after ST and WT. Maximal
      systolic blood pressure, heart rate, and rate pressure product did not change in
      either group, although maximal exercise time increased similarly in the ST and WT
      groups (+31 +/- 19 %, and +31 +/- 32 %, respectively, P < .01). CONCLUSIONS:
      Strength and walking trainings promoted similar increases in walking capacity and
      decreases in resting and submaximal exercise cardiovascular load.

PMID- 21948783
TI  - Trends in lower extremity surgical and endovascular revascularization in Germany.
AB  - BACKGROUND: We analyzed trends in lower extremity endovascular and open surgical
      procedures in hospitalized patients in Germany. PATIENTS AND METHODS: We used
      national statistics (DRG statistics) published by the Federal Statistical Office
      including data from almost all hospitals in Germany to calculate annual procedure
      rates of lower extremity endovascular and open surgical procedures in the years
      2005 to 2008. Detailed lists of the OPS-codes 8 - 836, 5 - 381, 5 - 393 separated
      by the 6th number of the code were analyzed regarding procedures representing
      revascularization of peripheral arteries including the aorta. RESULTS: Between
      2005 and 2008 the total number of endovascular procedures increased from 73,584
      to 98,664 and the number of surgical procedures from 74,789 to 86,172 a year. Age
      adjusted incidence rates of endovascular procedures in people >= 65 years
      increased from 325 to 432 per 100,000 while the incidence rates of all open
      surgical procedures increased from 315 to 351 per 100.000. Looking only at bypass
      surgery the incidence remained unchanged with 177 and 176 per 100,000 in the same
      period. Endovascular procedures other than balloon angioplasty including
      percutaneous atherectomy, laser recanalization or usage of cutting balloon,
      account for less than 1 % in Germany. CONCLUSIONS: The numbers of endovascular
      procedures overweigh the numbers of open surgical procedures for treatment of
      lower extremity PAD in Germany today. In contrast to data from the USA we could
      not demonstrate a decrease of open surgical procedures in Germany in recent
      years.

PMID- 21948784
TI  - Carotid endarterectomy in patients with foetal-type posterior circle of Willis:
      is there an indication for local anaesthesia?
AB  - Foetal-type posterior circle of Willis is a common anatomical variation with a
      variable degree of vessel asymmetry. In patients with this abnormality, carotid
      endarterectomy (CEA) may create cerebral hypo-perfusion intraoperatively, and
      this may be underestimated under general anaesthesia. There is currently no
      evidence that anatomical variations in the circle of Willis represent an
      independent risk factor for stroke. Moreover, there is a paucity of data on
      treating patients with such anatomical variations and co-existing ICA stenosis.
      We present a case of CEA under local anaesthesia (LA) in a 52-year-old female
      patient with symptomatic stenosis of the right ICA and coexistent foetal-type
      posterior circle of Willis. There were no post-operative complications and she
      was discharged free from symptoms. She was seen again 3 months later and was free
      from complications. This case higlights that LA should be strongly considered to
      enable better intra-operative neurological monitoring in the event of foetal-type
      posterior circle of Willis.

PMID- 21948785
TI  - EkoSonicSV endovascular system for recanalization of the basilar artery
      occlusion.
AB  - The interventional management of stroke may consist of the use of angioplasty,
      stenting or mechanical thrombus removal technique. For this purpose several
      retrieval devices are being used. Recently the new alternative device -
      EkoSonicSV has been introduced, which is particularly suitable for recanalization
      of the occluded basilar artery (BA). Here we are presenting a complete
      recanalization of BA using this device in two patients with stroke over a short
      period of time together with the intra-arterial use of recombinant tissue
      plasminogen activator and application of intravascular ultrasound.

PMID- 21948786
TI  - Iatrogenic pseudoaneurysm of the popliteal artery following corrective tibial
      osteotomy.
AB  - Due to its anatomical location the popliteal artery is exposed to injury during
      surgical procedures in the region of the knee joint, in particular during high
      level corrective osteotomies of the proximal tibial epiphysis. Nevertheless,
      posttraumatic (iatrogenic) pseudoaneurysm constitutes a very rare complication of
      the procedure. Only few reports of such complication have been published and they
      were usually connected with lateral tibial osteotomy - the accidents after medial
      osteotomy are seldom. The complication we report was observed in a 52-year-old
      female patient after corrective osteotomy of the medial portion of the proximal
      tibial epiphysis. The complication was diagnosed 7 days after surgery on US
      examination and subsequently confirmed by emergently performed angio-CT. The
      patient was referred for urgent reconstructive surgery. No significant
      complications were observed, neither postoperatively nor during follow-up visits.

PMID- 21948787
TI  - Fever of unknown origin: Importance of 18F-FDG PET/CT in the diagnosis of a late
      infectious complication after aneurysm bypass.
AB  - Persistent blood flow in aneurysmal sac after bypass-exclusion is well documented
      in the literature. Aneurysm enlargement, local compressive symptoms and even sac
      rupture are commonly described complications. Late secondary infection of
      popliteal artery aneurysm (PAA) following ligation and venous bypass is
      exceptional. We report the case of late PAA infection six years after bypass
      exclusion in a 75 year-old man which was diagnosed by 18F-FDG PET/CT. The patient
      was successfully treated by aneurysm resection and antibiotics. The diagnosis of
      popliteal aneurysm infection is often clinical, echographic and sonographic, but
      computed tomography scan can be false negative in chronic low-grade infection.
      18F-FDG PET/CT is able to accurately diagnose and localize infection with high
      sensibility and specificity.

PMID- 21948789
TI  - High expression of Lifeact in Arabidopsis thaliana reduces dynamic reorganization
      of actin filaments but does not affect plant development.
AB  - Lifeact is a novel probe that labels actin filaments in a wide range of
      organisms. We compared the localization and reorganization of Lifeact:Venus
      labeled actin filaments in Arabidopsis root hairs and root epidermal cells of
      lines that express different levels of Lifeact: Venus with that of actin
      filaments labeled with GFP:FABD2, a commonly used probe in plants. Unlike
      GFP:FABD2, Lifeact:Venus labeled the highly dynamic fine F-actin in the subapical
      region of tip-growing root hairs. Lifeact:Venus expression at varying levels was
      not observed to affect plant development. However, at expression levels
      comparable to those of GFP:FABD2 in a well-characterized marker line,
      Lifeact:Venus reduced reorganization rates of bundles of actin filaments in root
      epidermal cells. Reorganization rates of cytoplasmic strands, which reflect the
      reorganization of the actin cytoskeleton, were also reduced in these lines.
      Moreover, in the same line, Lifeact:Venus-decorated actin filaments were more
      resistant to depolymerization by latrunculin B than those in an equivalent
      GFP:FABD2-expressing line. In lines where Lifeact: Venus is expressed at lower
      levels, these effects are less prominent or even absent. We conclude that
      Lifeact: Venus reduces remodeling of the actin cytoskeleton in Arabidopsis in a
      concentration-dependent manner. Since this reduction occurs at expression levels
      that do not cause defects in plant development, selection of normally growing
      plants is not sufficient to determine optimal Lifeact expression levels. When
      correct expression levels of Lifeact have been determined, it is a valuable probe
      that labels dynamic populations of actin filaments such as fine F-actin, better
      than FABD2 does.

PMID- 21948790
TI  - Transcriptional activation by mitochondrial transcription factor A involves
      preferential distortion of promoter DNA.
AB  - Mitochondrial transcription factor A (mtTFA/TFAM) is a nucleus-encoded, high
      mobility-group-box (HMG-box) protein that regulates transcription of the
      mitochondrial genome by specifically recognizing light-strand and heavy-strand
      promoters (LSP, HSP1). TFAM also binds mitochondrial DNA in a non-sequence
      specific (NSS) fashion and facilitates its packaging into nucleoid structures.
      However, the requirement and contribution of DNA-bending for these two different
      binding modes has not been addressed in detail, which prompted this comparison of
      binding and bending properties of TFAM on promoter and non-promoter DNA. Promoter
      DNA increased the stability of TFAM to a greater degree than non-promoter DNA.
      However, the thermodynamic properties of DNA binding for TFAM with promoter and
      non-specific (NS) DNA were similar to each other and to other NSS HMG-box
      proteins. Fluorescence resonance energy transfer assays showed that TFAM bends
      promoter DNA to a greater degree than NS DNA. In contrast, TFAM lacking the C
      terminal tail distorted both promoter and non-promoter DNA to a significantly
      reduced degree, corresponding with markedly decreased transcriptional activation
      capacity at LSP and HSP1 in vitro. Thus, the enhanced bending of promoter DNA
      imparted by the C-terminal tail is a critical component of the ability of TFAM to
      activate promoter-specific initiation by the core mitochondrial transcription
      machinery.

PMID- 21948791
TI  - RNA-binding protein HuR autoregulates its expression by promoting alternative
      polyadenylation site usage.
AB  - RNA-binding protein HuR modulates the stability and translational efficiency of
      messenger RNAs (mRNAs) encoding essential components of the cellular
      proliferation, growth and survival pathways. Consistent with these functions, HuR
      levels are often elevated in cancer cells and reduced in senescent and quiescent
      cells. However, the molecular mechanisms that control HuR expression are poorly
      understood. Here we show that HuR protein autoregulates its abundance through a
      negative feedback loop that involves interaction of the nuclear HuR protein with
      a GU-rich element (GRE) overlapping with the HuR major polyadenylation signal
      (PAS2). An increase in the cellular HuR protein levels stimulates the expression
      of long HuR mRNA species containing an AU-rich element (ARE) that destabilizes
      the mRNAs and thus reduces the protein production output. The PAS2 read-through
      occurs due to a reduced recruitment of the CstF-64 subunit of the pre-mRNA
      cleavage stimulation factor in the presence of the GRE-bound HuR. We propose that
      this mechanism maintains HuR homeostasis in proliferating cells. Since only the
      nuclear HuR is expected to contribute to the auto-regulation, our model may
      explain the longstanding observation that the increase in the total HuR
      expression in cancer cells often correlates with the accumulation of its
      substantial fraction in the cytoplasm.

PMID- 21948792
TI  - BMUG@Sbase--a microbial gene expression and comparative genomic database.
AB  - The reducing cost of high-throughput functional genomic technologies is creating
      a deluge of high volume, complex data, placing the burden on bioinformatics
      resources and tool development. The Bacterial Microarray Group at St George's
      (BMUG@S) has been at the forefront of bacterial microarray design and analysis
      for over a decade and while serving as a hub of a global network of microbial
      research groups has developed BMUG@Sbase, a microbial gene expression and
      comparative genomic database. BMUG@Sbase (http://bugs.sgul.ac.uk/bugsbase/) is a
      web-browsable, expertly curated, MIAME-compliant database that stores
      comprehensive experimental annotation and multiple raw and analysed data formats.
      Consistent annotation is enabled through a structured set of web forms, which
      guide the user through the process following a set of best practices and
      controlled vocabulary. The database currently contains 86 expertly curated
      publicly available data sets (with a further 124 not yet published) and full
      annotation information for 59 bacterial microarray designs. The data can be
      browsed and queried using an explorer-like interface; integrating intuitive tree
      diagrams to present complex experimental details clearly and concisely.
      Furthermore the modular design of the database will provide a robust platform for
      integrating other data types beyond microarrays into a more Systems analysis
      based future.

PMID- 21948793
TI  - Therapeutic target database update 2012: a resource for facilitating target
      oriented drug discovery.
AB  - Knowledge and investigation of therapeutic targets (responsible for drug
      efficacy) and the targeted drugs facilitate target and drug discovery and
      validation. Therapeutic Target Database (TTD,
      http://bidd.nus.edu.sg/group/ttd/ttd.asp) has been developed to provide
      comprehensive information about efficacy targets and the corresponding approved,
      clinical trial and investigative drugs. Since its last update, major improvements
      and updates have been made to TTD. In addition to the significant increase of
      data content (from 1894 targets and 5028 drugs to 2025 targets and 17,816 drugs),
      we added target validation information (drug potency against target, effect
      against disease models and effect of target knockout, knockdown or genetic
      variations) for 932 targets, and 841 quantitative structure activity relationship
      models for active compounds of 228 chemical types against 121 targets. Moreover,
      we added the data from our previous drug studies including 3681 multi-target
      agents against 108 target pairs, 116 drug combinations with their synergistic,
      additive, antagonistic, potentiative or reductive mechanisms, 1427 natural
      product-derived approved, clinical trial and pre-clinical drugs and cross-links
      to the clinical trial information page in the ClinicalTrials.gov database for 770
      clinical trial drugs. These updates are useful for facilitating target discovery
      and validation, drug lead discovery and optimization, and the development of
      multi-target drugs and drug combinations.

PMID- 21948794
TI  - Bayesian multiple-instance motif discovery with BAMBI: inference of recombinase
      and transcription factor binding sites.
AB  - Finding conserved motifs in genomic sequences represents one of essential
      bioinformatic problems. However, achieving high discovery performance without
      imposing substantial auxiliary constraints on possible motif features remains a
      key algorithmic challenge. This work describes BAMBI-a sequential Monte Carlo
      motif-identification algorithm, which is based on a position weight matrix model
      that does not require additional constraints and is able to estimate such motif
      properties as length, logo, number of instances and their locations solely on the
      basis of primary nucleotide sequence data. Furthermore, should biologically
      meaningful information about motif attributes be available, BAMBI takes advantage
      of this knowledge to further refine the discovery results. In practical
      applications, we show that the proposed approach can be used to find sites of
      such diverse DNA-binding molecules as the cAMP receptor protein (CRP) and Din
      family site-specific serine recombinases. Results obtained by BAMBI in these and
      other settings demonstrate better statistical performance than any of the four
      widely-used profile-based motif discovery methods: MEME, BioProspector with
      BioOptimizer, SeSiMCMC and Motif Sampler as measured by the nucleotide-level
      correlation coefficient. Additionally, in the case of Din-family recombinase
      target site discovery, the BAMBI-inferred motif is found to be the only one
      functionally accurate from the underlying biochemical mechanism standpoint. C++
      and Matlab code is available at http://www.ee.columbia.edu/~guido/BAMBI or
      http://genomics.lbl.gov/BAMBI/.

PMID- 21948795
TI  - Methods for L-ribooligonucleotide sequence determination using LCMS.
AB  - The ability to verify the sequence of a nucleic acid-based therapeutic is an
      essential step in the drug development process. The challenge associated with
      sequence identification increases with the length and nuclease resistance of the
      nucleic acid molecule, the latter being an important attribute of therapeutic
      oligonucleotides. We describe methods for the sequence determination of
      Spiegelmers, which are enantiomers of naturally occurring RNA with high
      resistance to enzymatic degradation. Spiegelmer sequencing is effected by
      affixing a label or hapten to the 5'-end of the oligonucleotide and chemically
      degrading the molecule in a controlled fashion to generate fragments that are
      then resolved and identified using liquid chromatography-mass spectrometry. The
      Spiegelmer sequence is then derived from these fragments. Examples are shown for
      two different Spiegelmers (NOX-E36 and NOX-A12), and the specificity of the
      method is shown using a NOX-E36 mismatch control.

PMID- 21948796
TI  - Retroviral GAG proteins recruit AGO2 on viral RNAs without affecting RNA
      accumulation and translation.
AB  - Cellular micro(mi)RNAs are able to recognize viral RNAs through imperfect micro
      homologies. Similar to the miRNA-mediated repression of cellular translation,
      this recognition is thought to tether the RNAi machinery, in particular Argonaute
      2 (AGO2) on viral messengers and eventually to modulate virus replication. Here,
      we unveil another pathway by which AGO2 can interact with retroviral mRNAs. We
      show that AGO2 interacts with the retroviral Group Specific Antigen (GAG) core
      proteins and preferentially binds unspliced RNAs through the RNA packaging
      sequences without affecting RNA stability or eliciting translation repression.
      Using RNAi experiments, we provide evidences that these interactions, observed
      with both the human immunodeficiency virus 1 (HIV-1) and the primate foamy virus
      1 (PFV-1), are required for retroviral replication. Taken together, our results
      place AGO2 at the core of the retroviral life cycle and reveal original AGO2
      functions that are not related to miRNAs and translation repression.

PMID- 21948797
TI  - The structural characterization of a prophage-encoded extracellular DNase from
      Streptococcus pyogenes.
AB  - The pathogenic bacterium Group A Streptococcus pyogenes produces several
      extracellular DNases that have been shown to facilitate invasive infection by
      evading the human host immune system. DNases degrade the chromatin in neutrophil
      extracellular traps, enabling the bacterium to evade neutrophil capture. Spd1 is
      a type I, nonspecific betabetaalpha/metal-dependent nuclease from Streptococcus
      pyogenes, which is encoded by the SF370.1 prophage and is likely to be expressed
      as a result of prophage induction. We present here the X-ray structure of this
      DNase in the wild-type and Asn145Ala mutant form. Through structural and sequence
      alignments as well as mutagenesis studies, we have identified the key residues
      His121, Asn145 and Glu164, which are crucial for Spd1 nucleolytic activity and
      shown the active site constellation. Our wild-type structure alludes to the
      possibility of a catalytically blocked dimeric form of the protein. We have
      investigated the multimeric nature of Spd1 using size-exclusion chromatography
      with multi-angle light scattering (SEC-MALLS) in the presence and absence of the
      divalent metal ion Mg(2+), which suggests that Spd1 exists in a monomeric form in
      solution.

PMID- 21948798
TI  - Nucleosome occupancy reveals regulatory elements of the CFTR promoter.
AB  - Access to regulatory elements of the genome can be inhibited by nucleosome core
      particles arranged along the DNA strand. Hence, sites that are accessible by
      transcription factors may be located by using nuclease digestion to identify the
      relative nucleosome occupancy of a genomic region. In order to define novel cis
      regulatory elements in the ~2.7-kb promoter region of the cystic fibrosis
      transmembrane conductance regulator (CFTR) gene, we define its nucleosome
      occupancy. This profile reveals the precise positions of nucleosome-free regions
      (NFRs), both cell-type specific and others apparently unrelated to CFTR
      expression level and offer the first high-resolution map of the chromatin
      structure of the entire CFTR promoter in relevant cell types. Several of these
      NFRs are strongly bound by nuclear factors in a sequence-specific manner, and
      directly influence CFTR promoter activity. Sequences within the NFR1 and NFR4
      elements are highly conserved in many human gene promoters. Moreover, NFR1
      contributes to promoter activity of another gene, angiopoietin-like 3 (ANGPTL3),
      while NFR4 is constitutively nucleosome-free in promoters genome wide. Conserved
      motifs within NFRs of the CFTR promoter also show a high level of protection from
      DNase I digestion genome-wide, and likely have important roles in the positioning
      of nucleosome core particles more generally.

PMID- 21948799
TI  - Mobilization of giant piggyBac transposons in the mouse genome.
AB  - The development of technologies that allow the stable delivery of large genomic
      DNA fragments in mammalian systems is important for genetic studies as well as
      for applications in gene therapy. DNA transposons have emerged as flexible and
      efficient molecular vehicles to mediate stable cargo transfer. However, the
      ability to carry DNA fragments >10 kb is limited in most DNA transposons. Here,
      we show that the DNA transposon piggyBac can mobilize 100-kb DNA fragments in
      mouse embryonic stem (ES) cells, making it the only known transposon with such a
      large cargo capacity. The integrity of the cargo is maintained during
      transposition, the copy number can be controlled and the inserted giant
      transposons express the genomic cargo. Furthermore, these 100-kb transposons can
      also be excised from the genome without leaving a footprint. The development of
      piggyBac as a large cargo vector will facilitate a wider range of genetic and
      genomic applications.

PMID- 21948800
TI  - A chemical genomics screen to discover genes that modulate neural stem cell
      differentiation.
AB  - The authors designed a chemical genomics screen with the aim of understanding
      genes and pathways that modulate neural stem/precursor cell differentiation.
      Multipotent mouse neural precursor cells isolated from cortices of embryonic day
      12 (E12) embryos were subjected to spontaneous differentiation triggered by
      growth factor withdrawal. A quantitative whole-well immunofluorescence assay was
      set up to screen tool compound sets to identify small molecules with potent, dose
      dependent, and reproducible effects on increasing neural stem cell
      differentiation toward neuronal lineage. Among the pro-neuronal compounds, kinase
      inhibitors were shown to exert pro-neuronal effect via a signaling pathway
      associated with the kinase. The global effect of hit compounds on modulating
      neuronal differentiation was confirmed by an in vivo mouse study and human neural
      stem cells culture. This study demonstrates that a phenotypic assay using cell
      type-specific antibody markers can be used for a large-scale compound screen to
      discover targets and pathways with impacts on differentiation of lineage
      restricted precursor cells toward specific lineages.

PMID- 21948801
TI  - High-throughput screening identifies a bisphenol inhibitor of SV40 large T
      antigen ATPase activity.
AB  - The authors conducted a high-throughput screening campaign for inhibitors of SV40
      large T antigen ATPase activity to identify candidate antivirals that target the
      replication of polyomaviruses. The primary assay was adapted to 1536-well
      microplates and used to screen the National Institutes of Health Molecular
      Libraries Probe Centers Network library of 306 015 compounds. The primary screen
      had an Z value of ~0.68, signal/background = 3, and a high (5%) DMSO tolerance.
      Two counterscreens and two secondary assays were used to prioritize hits by
      EC(50), cytotoxicity, target specificity, and off-target effects. Hits that
      inhibited ATPase activity by >44% in the primary screen were tested in dose
      response efficacy and eukaryotic cytotoxicity assays. After evaluation of hit
      cytotoxicity, drug likeness, promiscuity, and target specificity, three compounds
      were chosen for chemical optimization. Chemical optimization identified a class
      of bisphenols as the most effective biochemical inhibitors. Bisphenol A inhibited
      SV40 large T antigen ATPase activity with an IC(50) of 41 uM in the primary assay
      and 6.2 uM in a cytoprotection assay. This compound class is suitable as probes
      for biochemical investigation of large T antigen ATPase activity, but because of
      their cytotoxicity, further optimization is necessary for their use in studying
      polyomavirus replication in vivo.

PMID- 21948802
TI  - Oncogenic and tumor suppressor functions of Notch in cancer: it's NOTCH what you
      think.
AB  - Notch signaling is often considered a model hematopoietic proto-oncogene because
      of its role as the main trigger of T cell acute lymphoblastic leukemia (T-ALL).
      Although its role in T-ALL is well characterized and further supported by a high
      frequency of activating NOTCH1 mutations in T-ALL patients, it still remains an
      open question whether the effects of Notch signaling are causative in other types
      of cancer, including solid tumors. Growing evidence supported by recent studies
      unexpectedly shows that Notch signaling can also have a potent tumor suppressor
      function in both solid tumors and hematological malignancies. We discuss the
      intriguing possibility that the pleiotropic functions of Notch can be tumor
      suppressive or oncogenic depending on the cellular context.

PMID- 21948803
TI  - Hiding the road signs that lead to tumor immunity.
AB  - Tumors exploit many strategies to evade T cell-mediated destruction. For example,
      tumors can prevent T cell infiltration by modifying gene expression in the
      endothelial cells and pericytes that form their vasculature. New work showing
      that the T cell-attracting chemokine CCL2 can be posttranslationally modified in
      the tumor microenvironment adds another mechanism to the already formidable
      arsenal of immunoevasion tactics used by solid tumors.

PMID- 21948804
TI  - Effectiveness of testing for genetic susceptibility to smoking-related diseases
      on smoking cessation outcomes: a systematic review and meta-analysis.
AB  - OBJECTIVE: To examine whether genetic testing for smoking-related diseases
      benefits smoking cessation. DATA SOURCES: PubMed, EMBASE, ERIC, PsycINFO,
      PsychArticles, CiNAHL and socINDEX databases, the search engine Google Scholar,
      and key-author and reference list searches. Study selection Randomised controlled
      smoking cessation interventions using genetic testing for smoking-related
      diseases. DATA EXTRACTION: Consistent with the Cochrane guidelines, two reviewers
      completed the review process (initial n=139) in three phases, title selection
      (n=56), abstract selection (n=28) and whole paper selection (n=9). From these
      nine studies, each reviewer extracted information about outcome measures and
      statistical and methodological quality. Data synthesis Relevant data were
      abstracted from included papers and were subsequently subjected to meta-analysis.
      RESULTS: Interest in genetic testing was relatively high with 60-80% of smokers
      reporting to be interested. The authors observed positive short-term effects on
      risk perception, motivation to quit smoking and smoking cessation, but these
      effects fade at longer follow-ups. Importantly, the authors did not find any
      evidence of adverse effect of testing negative on the risk-predisposing gene.
      CONCLUSIONS: This systematic review does not provide solid evidence for the
      proposed beneficial effects of genetic testing for smoking-related diseases on
      smoking cessation, but does suggest the presence of an immediate motivational
      effect, such that genetic testing resulted in higher risk perception and more
      motivation to quit smoking.

PMID- 21948805
TI  - Movies with smoking make less money.
AB  - OBJECTIVE: To determine the relationship between presence of smoking in films and
      total box office receipts. METHODS: Regression analysis of box office receipts as
      a function of film rating, production budget, year of release and presence of
      smoking for 1232 films released in the USA between 2002 and 2010. RESULTS: R
      rated films made, on average, 87% (95% CI 83% to 90%) of what PG-13 films of
      similar smoking status made and smoking films made 87% (95% CI 79% to 96%) of
      what comparably rated smoke-free films made. Larger budget films made more money.
      There was no significant effect of release year or G/PG rating compared with PG
      13-rated movies. CONCLUSIONS: Because PG-13 films without smoking (median $48.6
      million) already make 41% more money at the box office than R-rated movies with
      smoking (median $34.4 million), implementing an R rating for smoking to remove it
      from youth-rated films will not conflict with the economic self-interest of
      producer-distributors.

PMID- 21948806
TI  - Businesses' voluntary pro-health tobacco policies: a review and research agenda.
AB  - Research on the role of businesses in tobacco control has focused primarily on
      retailers, advertising firms and the hospitality industry, all of which have
      tended to support tobacco industry interests and resist effective tobacco control
      policies. However, in several countries, businesses have a history of voluntarily
      adopting tobacco-related policies that may advance tobacco control objectives.
      These phenomena have received little research attention. Existing literature on
      businesses ending tobacco sales, instituting voluntary workplace smoking
      restrictions and establishing non-smoker only hiring policies was reviewed. A
      research agenda on voluntary business initiatives would enhance and complement
      research on mandatory tobacco control policies by identifying new advocacy
      opportunities; suggesting avenues for strengthening or reinforcing existing
      policy initiatives; laying the groundwork for new mandatory policies; helping to
      inform ethical debates about contentious voluntary policies; and contributing to
      a better understanding of how alliances between the tobacco industry and other
      businesses might be weakened.

PMID- 21948807
TI  - Measuring the effect of cigarette plain packaging on transaction times and
      selection errors in a simulation experiment.
AB  - INTRODUCTION: Australia has introduced legislation to force all cigarette
      packaging to be generic from 2012 onwards. The tobacco retail industry estimates
      this will result in transaction times increasing by 15-45 s per pack and is
      spending at least $A10 million of tobacco industry funds on an advertising
      campaigns claiming that the increased time and errors associated with plain
      packaging will ultimately cost small businesses $A 461 million per annum and
      endanger 15,000 jobs. We undertook an objective experiment to test these claims.
      METHODOLOGY: Participants (n=52) were randomly assigned to stand in front of a
      display of either 50 plain or coloured cigarette packets and then were read a
      randomly ordered list of cigarette brands. The time participants took to locate
      each packet was recorded and all selection errors were noted. After 50
      'transactions', participants repeated the entire experiment with the alternative
      plain/coloured packs. Afterwards, participants were asked in an open-ended manner
      whether plain or coloured packaging was easier to locate and why. RESULTS: The
      average transaction was significantly quicker for plain compared with coloured
      packs (2.92 vs 3.17 s; p=0.040). One or more mistakes were made by 40.4% of
      participants when selecting coloured packaging compared with only 17.3% for plain
      packaging (p=0.011). Qualitative results suggested that the colours and
      inconsistent location of brand names often served to distract when participants
      scanned for brands. CONCLUSION: Rather than plain packaging requiring an
      additional 45 s per transaction, our results suggest that it will, if anything,
      modestly decrease transaction times and selection errors.

PMID- 21948808
TI  - Integrated trauma treatment in correctional health care and community-based
      treatment upon reentry.
AB  - Given the crisis of mass incarceration in the United States and the high
      prevalence of trauma histories among those incarcerated, it is imperative to
      improve service delivery to inmates in correctional facilities and to those
      undergoing reentry in community-based treatment settings. This article provides
      trauma definitions and categories, describes the sequelae of trauma, reviews
      research on the high prevalence of incarceration in this nation, and reviews
      research on the high prevalence of trauma among the incarcerated. This article
      also provides a menu of evidence-based and promising treatment approaches to
      address the overlap among trauma, mental illness, substance abuse, and behavioral
      problems. A synthesis of research via seven points is meant to guide practitioner
      and policy responses to the national challenge of meeting the needs of those
      undergoing reentry.

PMID- 21948809
TI  - Diagnosis of invasive fungal infections in hematology and oncology--guidelines
      from the Infectious Diseases Working Party in Haematology and Oncology of the
      German Society for Haematology and Oncology (AGIHO).
AB  - Invasive fungal infections (IFIs) are a primary cause of morbidity and mortality
      in patients with hematological malignancies. Establishing a definite diagnosis of
      IFI in immunocompromised patients is particularly challenging and time consuming,
      but delayed initiation of antifungal treatment increases mortality. The limited
      overall outcome has led to the strategy of initiating either 'empirical' or
      'preemptive' antifungal therapy before the final diagnosis. However, diagnostic
      procedures have been vastly improved in recent years. Particularly noteworthy is
      the introduction of newer imaging techniques and non-culture methods, including
      antigen-based assays, metabolite detection and molecular detection of fungal DNA
      from body fluid samples. Though varying widely in cancer patients, the risk of
      IFI is highest in those with allogeneic stem cell transplantation and those with
      acute leukemia. The AGIHO presents recommendations for the diagnosis of IFIs with
      risk-adapted screening concepts for febrile episodes in patients with haemato
      oncological disorders.

PMID- 21948810
TI  - Two sides of the medallion: poor treatment tolerance but better survival by
      standard chemotherapy in elderly patients with advanced-stage diffuse large B
      cell lymphoma.
AB  - BACKGROUND: We investigated treatment of unselected elderly patients with diffuse
      large B-cell lymphoma (DLBCL) and its subsequent impact on treatment tolerance
      and survival. PATIENTS AND METHODS: Data from all 419 advanced-stage DLBCL
      patients, aged 75 or older and newly diagnosed between 1997 and 2004, were
      included from five regional population-based cancer registries in The
      Netherlands. Subsequent data on comorbidity, performance status, treatment,
      motives for adaptations or refraining from chemotherapy and toxic effects was
      collected from the medical records. Follow-up was completed until 1st January
      2009. RESULTS: Only 46% of patients received the standard therapy [aggressive
      chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone
      (CHOP)-like chemotherapy]. Motives for withholding chemotherapy were refusal by
      patient/family, poor performance status or estimated short life expectancy. Of
      all patients receiving CHOP-like chemotherapy, only 56% could complete at least
      six cycles. Grade 3 or 4 toxicity occurred in 67% of patients receiving standard
      therapy. The independent effect of therapy on survival remained after correction
      for the age-adjusted International Prognostic Index. CONCLUSIONS: Standard
      therapy was applied less often in elderly patients with a subsequent independent
      negative impact on survival. Furthermore, high toxicity rate and the
      impossibility of the majority of patients to complete treatment were seen. This
      implies that better treatment strategies should be devised including a proper
      selection of senior patients for this aggressive chemotherapy.

PMID- 21948811
TI  - A phase II study of concurrent cetuximab-cisplatin and intensity-modulated
      radiotherapy in locoregionally advanced nasopharyngeal carcinoma.
AB  - BACKGROUND: Based on our previous work on the clinical activity of cetuximab in
      recurrent nasopharyngeal carcinoma (NPC), we evaluated the feasibility of adding
      cetuximab to concurrent cisplatin and intensity-modulated radiotherapy (IMRT) in
      locoregionally advanced NPC. PATIENTS AND METHODS: Patients with American Joint
      Committee on Cancer stage III-IVB NPC were given an initial dose of cetuximab
      (400 mg/m(2)) 7-10 days before receiving concurrent IMRT, weekly cisplatin (30
      mg/m(2)/week) and cetuximab (250 mg/m(2)/week). RESULTS: Thirty patients (median
      age of 45 years) with stage III (67%), IVA (30%) and IVB (3%) nonkeratinizing NPC
      were enrolled. Grade 3-4 oropharyngeal mucositis occurred in 26 (87%) patients
      and 10 (33%) patients required short-term nasogastric feeding. Grade 3
      radiotherapy-related dermatitis occurred in six patients (20%) and three patients
      (10%) had grade 3 cetuximab-related acneiform rash. These grade 3-4 skin and
      mucosal toxic effects were manageable and reversible. At a median follow-up of
      31.8 months [95% confidence interval (CI) 26.2-32.1 months], the 2-year
      progression-free survival was 86.5% (95% CI 74.3% to 98.8%). CONCLUSIONS:
      Concurrent administration of cetuximab, weekly cisplatin and IMRT is a feasible
      strategy against locoregionally advanced NPC. Preliminary survival data compare
      favorably with historic data and further follow-up is warranted.

PMID- 21948812
TI  - Acupuncture compared with placebo acupuncture in radiotherapy-induced nausea--a
      randomized controlled study.
AB  - BACKGROUND: It is not known if verum (real) acupuncture is effective for nausea
      and vomiting (emesis) during radiotherapy. PATIENTS AND METHODS: We randomly
      treated 215 blinded cancer patients with verum: penetrating 'deqi' creating
      acupuncture (n = 109) or non-penetrating sham needles (n = 106) two to three
      times per week. The patients documented emesis daily during the radiotherapy
      period. Primary end point was the number of patients with at least one episode of
      nausea. RESULTS: In the verum and the sham acupuncture group, 70% and 62%
      experienced nausea at least once during the radiotherapy period (relative risk
      1.1, 95% CI 0.9-1.4) for a mean number of 10.1 and 8.7 days. Twenty five percent
      and 28% vomited, and 42% and 37% used antiemetic drugs at least once,
      respectively. Ninety-five percent in the verum acupuncture group and 96% in the
      sham acupuncture group believed that the treatment had been effective against
      nausea. In both groups, 67% experienced positive effects on relaxation, mood,
      sleep or pain reduction and 89% wished to receive the treatment again.
      CONCLUSION: Acupuncture creating deqi is not more effective than sham in
      radiotherapy-induced nausea, but in this study, nearly all patients in both
      groups experienced that the treatment was effective for nausea.

PMID- 21948813
TI  - Prognostic value of preoperative radiological staging assessed by computed
      tomography in patients with nonmetastatic colon cancer.
AB  - PURPOSE: This study evaluated the prognostic value of preoperative locoregional
      staging in patients with colon cancer and who underwent curative resection.
      METHODS: A total of 536 consecutive patients who underwent curative resection for
      colon cancer from February 1999 to November 2007 were prospectively enrolled. The
      clinicopathological variables, including the radiological staging using computed
      tomography, were analyzed for the prognostic significance. RESULTS: The 5-year
      overall survival rates of the patients with radiological T1, T2, T3, and T4 were
      96%, 89%, 75%, and 79%, respectively (P = 0.028). The 5-year overall survival
      rates were 83%, 76%, and 54%, respectively, for patients with radiological N0,
      N1, and N2 disease (P < 0.001). The 5-year overall survival rates of the patients
      with radiological TNM (tumor-node-metastasis) stages I, II, and III were 90%,
      81%, and 70%, respectively (P < 0.001) and the 5-year overall survival rates of
      the patients with pathological TNM stages I, II, and III were 93%, 80%, and 70%,
      respectively (P = 0.001). On multivariate analysis, the radiological T and N
      categories remained independent prognostic factors for both overall survival and
      disease-free survival. CONCLUSION: Radiological staging is an independent
      predictor of long-term survival in the preoperative setting.

PMID- 21948814
TI  - Intensified chemotherapy with stem-cell rescue in germ-cell tumors.
AB  - BACKGROUND: Based on the high chemosensitivity of germ-cell tumors (GCTs), the
      concept of high-dose chemotherapy (HDCT) has been developed worldwide and
      investigated through many clinical trials. It has been carried out in different
      clinical settings, ranging from resistant or absolute refractory disease to
      chemosensitive relapse. HDCT with stem-cell support has been also explored as a
      part of first-line strategy for poor-prognosis patients. PATIENTS AND METHODS:
      Our review summarized results from clinical trials evaluating the role of HDCT in
      patients with advanced GCTs. So far available data were obtained through a
      Medline search of English-language literature. RESULTS: Several phase II trials
      and retrospective series have shown a possible benefit for GCT patients with
      recurrent disease as well as in first-line setting. Despite these results, data
      derived from randomized phase III studies failed to demonstrate any survival
      advantage for HDCT over conventional chemotherapy. CONCLUSIONS: The role of HDCT
      in GCTs remains controversial. We need new prospective studies based on
      prognostic factors with multiple transplants of carboplatin and etoposide as the
      preferred high dose regimen. At present, based mainly on retrospective and phase
      II studies, HDCT may represent a therapeutic option for patients with primary
      refractory disease or for those with a second or further relapse.

PMID- 21948815
TI  - Optimal prostate-specific antigen screening interval for prostate cancer.
AB  - BACKGROUND: To identify the optimal interval for repeat prostate-specific antigen
      (PSA) testing to screen for prostate cancer in healthy adults. PATIENTS AND
      METHODS: A retrospective cohort study was conducted on 7332 healthy males without
      prostate cancer at baseline from 2005 to 2008. Participants underwent annual
      health checkups including PSA testing at the Center for Preventive Medicine in
      Japan. Participants with high PSA (>= 4.0 ng/ml) underwent further examination
      for prostate cancer. A subgroup analysis was conducted age group (<50 years, >=
      50 years). RESULTS: Mean age was 50 years. Mean PSA at baseline was 1.2 ng/ml. In
      over 50-year group, for those with initial PSA of <1.0, 1.0-1.9, 2.0-2.9, and 3.0
      3.9 ng/ml at baseline, the 3-year cumulative incidence of prostate cancer was 0%,
      0.1%, 0.3%, and 5.7%, respectively. No prostate cancer was identified in those
      <50 years, regardless of PSA level. CONCLUSIONS: If PSA screening is recommended,
      males >50 years with PSA of 3.0-3.9 ng/ml at baseline should undergo rescreening
      at 2 years. For men with PSA <3.0 ng/ml, PSA rescreening at intervals of >= 3
      years is appropriate. PSA screening may not be indicated in males of <50 years of
      age.

PMID- 21948816
TI  - The end of the beginning of personalized medicine.

PMID- 21948817
TI  - Regional variations in public opinion on the affordable care act.
AB  - One year after passage, the Patient Protection and Affordable Care Act (ACA)
      remains a divisive topic. Most publicly released polls on the law have focused on
      the views of Americans as a whole. But with much of the responsibility of
      implementation lying with the states, this essay explores whether opinion differs
      geographically. The analysis finds that views on the health reform law do differ
      by region, and these differences are most likely driven by the political leanings
      of a given area. While opinion nationally differs by age and race, this pattern
      does not hold when looking by region. Areas that have a larger share of uninsured
      and are slated to receive greater federal funding under the ACA also do not
      differ in their opinions. These data suggest that regional variations in
      attitudes about the ACA are based less on the demographic structure of a region
      and more on the political ideologies of residents in a given region. As
      implementation of the law continues, this analysis shows that national opinion
      data mask important regional variations in views of the ACA.

PMID- 21948818
TI  - Who deserves health care? The effects of causal attributions and group cues on
      public attitudes about responsibility for health care costs.
AB  - This research investigates the impact of cues about ascriptive group
      characteristics (race, class, gender) and the causes of ill health (health
      behaviors, inborn biological traits, social systemic factors) on beliefs about
      who deserves society's help in paying for the costs of medical treatment. Drawing
      on data from three original vignette experiments embedded in a nationally
      representative survey of American adults, we find that respondents are reluctant
      to blame or deny societal support in response to explicit cues about racial
      attributes--but equally explicit cues about the causal impact of individual
      behaviors on health have large effects on expressed attitudes. Across all three
      experiments, a focus on individual behavioral causes of illness is associated
      with increased support for individual responsibility for health care costs and
      lower support for government-financed health insurance. Beliefs about social
      groups and causal attributions are, however, tightly intertwined. We find that
      when groups suffering ill health are defined in racial, class, or gender terms,
      Americans differ in their attribution of health disparities to individual
      behaviors versus biological or systemic factors. Because causal attributions also
      affect health policy opinions, varying patterns of causal attribution may
      reinforce group stereotypes and undermine support for universal access to health
      care.

PMID- 21948819
TI  - Red state, blue state, flu state: media self-selection and partisan gaps in Swine
      flu vaccinations.
AB  - This study assesses the relationship between political partisanship and attitudes
      and behavior with respect to the H1N1 virus (swine flu) crisis of 2009 in
      general, and the U.S. mass vaccination program in particular. I argue that even
      seemingly nonpartisan political issues like public health are increasingly
      characterized by partisan polarization in public attitudes and that such
      polarization is attributable, at least partly, to the breakdown of the
      information commons that characterized the U.S. mass media from roughly the 1950s
      until the early 1990s. In its place has arisen an increasingly fragmented and
      niche-oriented media marketplace in which individuals are better able to limit
      their information exposure to attitudes and opinions that reinforce, rather than
      challenge, their preexisting beliefs. I test my argument against a variety of
      data sources, including opinion surveys and state-level swine flu vaccination
      rate data.

PMID- 21948820
TI  - Public opinion, health policy, and American politics. Editors' introduction.

PMID- 21948821
TI  - Making the best of hard times: how the nation's economic circumstances shaped the
      public's embrace of health care reform.
AB  - The U.S. Congress enacted expansive (and expensive) health care reforms amid the
      worst economic downturn since the Great Depression. Public acquiescence provided
      crucial political cover; elites on both sides struggled mightily to sway popular
      opinion. Were reformers' efforts made easier or more difficult by the tough
      economic times? Using newly available data on Americans' perceptions of economic
      insecurity and attitudes toward public policy, this article explores the
      relationship between economic circumstances and political attitudes. The findings
      suggest that the Great Recession both facilitated and impeded efforts to rally
      the public in favor of reform: perceptions of past declines in the U.S. economy
      bolstered government intervention, but household economic insecurity both
      distracted attention from large medical expenses (which otherwise legitimized
      collective action) and undermined Americans' support for additional government
      spending. Equally consequential, reformers' efforts to adapt to economic
      stringency by portraying reform as exclusively about affordability missed
      opportunities for broadening popular support for these interventions; in the
      longer run this may, unless corrected, prove a decisive misstep in shepherding
      the Patient Protection and Affordable Care Act through its long time line of
      implementation.

PMID- 21948822
TI  - Salmonella enterica in swine production: assessing the association between
      amplified fragment length polymorphism and epidemiological units of concern.
AB  - The aims of this study were to determine the ability of amplified fragment length
      polymorphism (AFLP) to differentiate Salmonella isolates from different units of
      swine production and to demonstrate the relatedness of Salmonella between farms
      and abattoirs by AFLP. Twenty-four farms in the midwestern United States were
      visited four times from 2006 to 2009. At each farm or abattoir visit, 30 fecal
      samples or 30 mesenteric lymph nodes were collected, respectively. A total of 220
      Salmonella isolates were obtained, serotyped, and genotyped by multilocus
      sequence typing (MLST) and AFLP. These 220 isolates clustered into 21 serotypes,
      18 MLST types, and 14 predominant AFLP clusters based on a genetic similarity
      threshold level of 60%. To assess genetic differentiation between farms, harvest
      cohorts, and pigs, analysis of molecular variance was conducted using AFLP data.
      The results showed 65.62% of overall genetic variation was attributed to variance
      among pigs, 27.21% to farms, and 7.17% to harvest cohorts. Variance components at
      the farm (P = 0.003) and pig (P = 0.001) levels were significant, but not at the
      harvest cohort level (P = 0.079). A second analysis, a permutation test using
      AFLP data, indicated that on-farm and at-abattoir Salmonella from pigs of the
      same farms were more related than from different farms. Therefore, among the
      three subtyping methods, serotyping, MLST, and AFLP, AFLP was the method that was
      able to differentiate among Salmonella isolates from different farms and link
      contamination at the abattoir to the farm of origin.

PMID- 21948823
TI  - Diversity and abundance of single-stranded DNA viruses in human feces.
AB  - In this study, we investigated the abundance and diversity of single-stranded DNA
      (ssDNA) viruses in fecal samples from five healthy individuals through a
      combination of serial filtration and CsCl gradient ultracentrifugation. Virus
      abundance ranged from 108 to 109 per gram of feces, and virus-to-bacterium ratios
      were much lower (less than 0.1) than those observed in aquatic environments (5 to
      10). Viral DNA was extracted and randomly amplified using phi29 polymerase and
      analyzed through high-throughput 454 pyrosequencing. Among 400,133 sequences, an
      average of 86.2% viromes were previously uncharacterized in public databases.
      Among previously known viruses, double-stranded DNA podophages (52 to 74%),
      siphophages (11 to 30%), myophages (1 to 4%), and ssDNA microphages (3 to 9%)
      were major constituents of human fecal viromes. A phylogenetic analysis of 24
      large contigs of microphages based on conserved capsid protein sequences revealed
      five distinct newly discovered evolutionary microphage groups that were distantly
      related to previously known microphages. Moreover, putative capsid protein
      sequences of five contigs were closely related to prophage-like sequences in the
      genomes of three Bacteroides and three Prevotella strains, suggesting that
      Bacteroides and Prevotella are the sources of infecting microphages in their
      hosts.

PMID- 21948824
TI  - Metabolome remodeling during the acidogenic-solventogenic transition in
      Clostridium acetobutylicum.
AB  - The fermentation carried out by the biofuel producer Clostridium acetobutylicum
      is characterized by two distinct phases. Acidogenesis occurs during exponential
      growth and involves the rapid production of acids (acetate and butyrate).
      Solventogenesis initiates as cell growth slows down and involves the production
      of solvents (butanol, acetone, and ethanol). Using metabolomics, isotope tracers,
      and quantitative flux modeling, we have mapped the metabolic changes associated
      with the acidogenic-solventogenic transition. We observed a remarkably ordered
      series of metabolite concentration changes, involving almost all of the 114
      measured metabolites, as the fermentation progresses from acidogenesis to
      solventogenesis. The intracellular levels of highly abundant amino acids and
      upper glycolytic intermediates decrease sharply during this transition. NAD(P)H
      and nucleotide triphosphates levels also decrease during solventogenesis, while
      low-energy nucleotides accumulate. These changes in metabolite concentrations are
      accompanied by large changes in intracellular metabolic fluxes. During
      solventogenesis, carbon flux into amino acids, as well as flux from pyruvate (the
      last metabolite in glycolysis) into oxaloacetate, decreases by more than 10-fold.
      This redirects carbon into acetyl coenzyme A, which cascades into
      solventogenesis. In addition, the electron-consuming reductive tricarboxylic acid
      (TCA) cycle is shutdown, while the electron-producing oxidative (clockwise) right
      side of the TCA cycle remains active. Thus, the solventogenic transition involves
      global remodeling of metabolism to redirect resources (carbon and reducing power)
      from biomass production into solvent production.

PMID- 21948825
TI  - Activity-based metagenomic screening and biochemical characterization of bovine
      ruminal protozoan glycoside hydrolases.
AB  - The rumen, the foregut of herbivorous ruminant animals such as cattle, functions
      as a bioreactor to process complex plant material. Among the numerous and diverse
      microbes involved in ruminal digestion are the ruminal protozoans, which are
      single-celled, ciliated eukaryotic organisms. An activity-based screen was
      executed to identify genes encoding fibrolytic enzymes present in the
      metatranscriptome of a bovine ruminal protozoan-enriched cDNA expression library.
      Of the four novel genes identified, two were characterized in biochemical assays.
      Our results provide evidence for the effective use of functional metagenomics to
      retrieve novel enzymes from microbial populations that cannot be maintained in
      axenic cultures.

PMID- 21948826
TI  - Use of stable isotopes to measure the metabolic activity of the human intestinal
      microbiota.
AB  - The human intestinal microbiota is a complex biological system comprising a vast
      repertoire of microbes with considerable metabolic activity relevant to both
      bacterial growth and host health. Greater strides have been made in the analysis
      of microbial diversity than in the measurement of functional activity,
      particularly in vivo. Stable isotope probing offers a new approach by coupling
      measurements of metabolic activity with microbial identification. Using a low
      enrichment labeling strategy in vitro, this study has identified metabolically
      active bacterial groups via magnetic-bead capture methodology and stable isotope
      ratio analysis. Using five probes (EUB338, Bac303, Bif164, EREC482, and Clep866),
      changes in the activities of key intestinal microbial groups were successfully
      measured by exploiting tracers of de novo RNA synthesis. Perturbation of the
      nutrient source with oligofructose generated changes in the activity of
      bifidobacteria as expected, but also in the Bacteroides-Prevotella group, the
      Eubacterium rectale-Clostridium coccoides group, and the Clostridium leptum
      subgroup. Changes in activity were also observed in response to the medium type.
      This study suggests that changes in the functional activity of the gut microbiota
      can be assessed using tracers of de novo nucleic acid synthesis combined with
      measurement of low isotopic enrichment in 16S rRNA. Such tracers potentially
      limit substrate bias because they are universally available to bacteria. This low
      enrichment labeling approach does not depend on the commercial availability of
      specific labeled substrates and can be easily translated to in vivo probing
      experiments of the functional activity of the microbiota in the human gut.

PMID- 21948827
TI  - Identification and characterization of a novel class of extracellular poly(3
      hydroxybutyrate) depolymerase from Bacillus sp. strain NRRL B-14911.
AB  - The catalytic, linker, and denatured poly(3-hydroxybutyrate) (dPHB)-binding
      domains of bacterial extracellular PHB depolymerases (PhaZs) are classified into
      several different types. We now report a novel class of extracellular PHB
      depolymerase from Bacillus sp. strain NRRL B-14911. Its catalytic domain belongs
      to type 1, whereas its putative linker region neither possesses the sequence
      features of the three known types of linker domains nor exhibits significant
      amino acid sequence similarity to them. Instead, this putative linker region can
      be divided into two distinct linker domains of novel types: LD1 and LD2. LD1
      shows significant amino acid sequence similarity to certain regions of a large
      group of PHB depolymerase-unrelated proteins. LD2 and its homologs are present in
      a small group of PhaZs. The remaining C-terminal portion of this PhaZ can be
      further divided into two distinct domains: SBD1 and SBD2. Each domain showed
      strong binding to dPHB, and there is no significant sequence similarity between
      them. Each domain neither possesses the sequence features of the two known types
      of dPHB-binding domains nor shows significant amino acid sequence similarity to
      them. These unique features indicate the presence of two novel and distinct types
      of dPHB-binding domains. Homologs of these novel domains also are present in the
      extracellular PhaZ of Bacillus megaterium and the putative extracellular PhaZs of
      Bacillus pseudofirmus and Bacillus sp. strain SG-1. The Bacillus sp. NRRL B-14911
      PhaZ appears to be a representative of a novel class of extracellular PHB
      depolymerases.

PMID- 21948828
TI  - Evaluation of a transposase protocol for rapid generation of shotgun high
      throughput sequencing libraries from nanogram quantities of DNA.
AB  - Construction of DNA fragment libraries for next-generation sequencing can prove
      challenging, especially for samples with low DNA yield. Protocols devised to
      circumvent the problems associated with low starting quantities of DNA can result
      in amplification biases that skew the distribution of genomes in metagenomic
      data. Moreover, sample throughput can be slow, as current library construction
      techniques are time-consuming. This study evaluated Nextera, a new transposon
      based method that is designed for quick production of DNA fragment libraries from
      a small quantity of DNA. The sequence read distribution across nine phage genomes
      in a mock viral assemblage met predictions for six of the least-abundant phages;
      however, the rank order of the most abundant phages differed slightly from
      predictions. De novo genome assemblies from Nextera libraries provided long
      contigs spanning over half of the phage genome; in four cases where full-length
      genome sequences were available for comparison, consensus sequences were found to
      match over 99% of the genome with near-perfect identity. Analysis of areas of low
      and high sequence coverage within phage genomes indicated that GC content may
      influence coverage of sequences from Nextera libraries. Comparisons of phage
      genomes prepared using both Nextera and a standard 454 FLX Titanium library
      preparation protocol suggested that the coverage biases according to GC content
      observed within the Nextera libraries were largely attributable to bias in the
      Nextera protocol rather than to the 454 sequencing technology. Nevertheless,
      given suitable sequence coverage, the Nextera protocol produced high-quality data
      for genomic studies. For metagenomics analyses, effects of GC amplification bias
      would need to be considered; however, the library preparation standardization
      that Nextera provides should benefit comparative metagenomic analyses.

PMID- 21948829
TI  - Broad-host-range plasmids from agricultural soils have IncP-1 backbones with
      diverse accessory genes.
AB  - Broad-host-range plasmids are known to spread genes between distinct phylogenetic
      groups of bacteria. These genes often code for resistances to antibiotics and
      heavy metals or degradation of pollutants. Although some broad-host-range
      plasmids have been extensively studied, their evolutionary history and genetic
      diversity remain largely unknown. The goal of this study was to analyze and
      compare the genomes of 12 broad-host-range plasmids that were previously isolated
      from Norwegian soils by exogenous plasmid isolation and that encode mercury
      resistance. Complete nucleotide sequencing followed by phylogenetic analyses
      based on the relaxase gene traI showed that all the plasmids belong to one of two
      subgroups (beta and epsilon) of the well-studied incompatibility group IncP-1. A
      diverse array of accessory genes was found to be involved in resistance to
      antimicrobials (streptomycin, spectinomycin, and sulfonamides), degradation of
      herbicides (2,4-dichlorophenoxyacetic acid and 2,4-dichlorophenoxypropionic
      acid), and a putative new catabolic pathway. Intramolecular transposition of
      insertion sequences followed by deletion was found to contribute to the diversity
      of some of these plasmids. The previous observation that the insertion sites of a
      Tn501-related element are identical in four IncP-1beta plasmids (pJP4, pB10,
      R906, and R772) was further extended to three more IncP-1beta plasmids (pAKD15,
      pAKD18, and pAKD29). We proposed a hypothesis for the evolution of these Tn501
      bearing IncP-1beta plasmids that predicts recent diversification followed by
      worldwide spread. Our study increases the available collection of complete IncP-1
      plasmid genome sequences by 50% and will aid future studies to enhance our
      understanding of the evolution and function of this important plasmid family.

PMID- 21948830
TI  - Phenotypic diversity caused by differential RpoS activity among environmental
      Escherichia coli isolates.
AB  - Enteric bacteria deposited into the environment by animal hosts are subject to
      diverse selective pressures. These pressures may act on phenotypic differences in
      bacterial populations and select adaptive mutations for survival in stress. As a
      model to study phenotypic diversity in environmental bacteria, we examined
      mutations of the stress response sigma factor, RpoS, in environmental Escherichia
      coli isolates. A total of 2,040 isolates from urban beaches and nearby fecal
      pollution sources on Lake Ontario (Canada) were screened for RpoS function by
      examining growth on succinate and catalase activity, two RpoS-dependent
      phenotypes. The rpoS sequence was determined for 45 isolates, including all
      candidate RpoS mutants, and of these, six isolates were confirmed as mutants with
      the complete loss of RpoS function. Similarly to laboratory strains, the RpoS
      expression of these environmental isolates was stationary phase dependent.
      However, the expression of RpoS regulon members KatE and AppA had differing
      levels of expression in several environmental isolates compared to those in
      laboratory strains. Furthermore, after plating rpoS+ isolates on succinate, RpoS
      mutants could be readily selected from environmental E. coli. Naturally isolated
      and succinate-selected RpoS mutants had lower generation times on poor carbon
      sources and lower stress resistance than their rpoS+ isogenic parental strains.
      These results show that RpoS mutants are present in the environment (with a
      frequency of 0.003 among isolates) and that, similarly to laboratory and
      pathogenic strains, growth on poor carbon sources selects for rpoS mutations in
      environmental E. coli. RpoS selection may be an important determinant of
      phenotypic diversification and, hence, the survival of E. coli in the
      environment.

PMID- 21948831
TI  - Linking specific heterotrophic bacterial populations to bioreduction of uranium
      and nitrate in contaminated subsurface sediments by using stable isotope probing.
AB  - Shifts in terminal electron-accepting processes during biostimulation of uranium
      contaminated sediments were linked to the composition of stimulated microbial
      populations using DNA-based stable isotope probing. Nitrate reduction preceded
      U(VI) and Fe(III) reduction in [13C]ethanol-amended microcosms. The predominant,
      active denitrifying microbial groups were identified as members of the
      Betaproteobacteria, whereas Actinobacteria dominated under metal-reducing
      conditions.

PMID- 21948832
TI  - Isolation and characterization of a psychropiezophilic alphaproteobacterium.
AB  - Cultivated psychropiezophilic (low-temperature- and high-pressure-adapted)
      bacteria are currently restricted to phylogenetically narrow groupings capable of
      growth under nutrient-replete conditions, limiting current knowledge of the
      extant functional attributes and evolutionary constraints of diverse
      microorganisms inhabiting the cold, deep ocean. This study documents the
      isolation of a deep-sea bacterium following dilution-to-extinction cultivation
      using a natural seawater medium at high hydrostatic pressure and low temperature.
      To our knowledge, this isolate, designated PRT1, is the slowest-growing (minimal
      doubling time, 36 h) and lowest cell density-producing (maximal densities of 5.0
      * 106 cells ml-1) piezophile yet obtained. Optimal growth was at 80 MPa,
      correlating with the depth of capture (8,350 m), and 10 degrees C, with average
      cell sizes of 1.46 MUm in length and 0.59 MUm in width. Through detailed growth
      studies, we provide further evidence for the temperature-pressure dependence of
      the growth rate for deep-ocean bacteria. PRT1 was phylogenetically placed within
      the Roseobacter clade, a bacterial lineage known for widespread geographic
      distribution and assorted lifestyle strategies in the marine environment.
      Additionally, the gene transfer agent (GTA) g5 capsid protein gene was amplified
      from PRT1, indicating a potential mechanism for increased genetic diversification
      through horizontal gene transfer within the hadopelagic environment. This study
      provides a phylogenetically novel isolate for future investigations of high
      pressure adaptation, expands the known physiological traits of cultivated members
      of the Roseobacter lineage, and demonstrates the feasibility of cultivating novel
      microbial members from the deep ocean using natural seawater.

PMID- 21948833
TI  - 4,6-alpha-glucanotransferase, a novel enzyme that structurally and functionally
      provides an evolutionary link between glycoside hydrolase enzyme families 13 and
      70.
AB  - Lactobacillus reuteri 121 uses the glucosyltransferase A (GTFA) enzyme to convert
      sucrose into large amounts of the alpha-D-glucan reuteran, an exopolysaccharide.
      Upstream of gtfA lies another putative glucansucrase gene, designated gtfB.
      Previously, we have shown that the purified recombinant GTFB protein/enzyme is
      inactive with sucrose. Various homologs of gtfB are present in other
      Lactobacillus strains, including the L. reuteri type strain, DSM 20016, the
      genome sequence of which is available. Here we report that GTFB is a novel alpha
      glucanotransferase enzyme with disproportionating (cleaving alpha1->4 and
      synthesizing alpha1->6 and alpha1->4 glycosidic linkages) and alpha1->6
      polymerizing types of activity on maltotetraose and larger maltooligosaccharide
      substrates (in short, it is a 4,6-alpha-glucanotransferase). Characterization of
      the types of compounds synthesized from maltoheptaose by matrix-assisted laser
      desorption ionization-time of flight mass spectrometry (MALDI-TOF MS),
      methylation analysis, and 1-dimensional 1H nuclear magnetic resonance (NMR)
      spectroscopy revealed that only linear products were made and that with
      increasing degrees of polymerization (DP), more alpha1->6 glycosidic linkages
      were introduced into the final products, ranging from 18% in the incubation
      mixture to 33% in an enriched fraction. In view of its primary structure, GTFB
      clearly is a member of the glycoside hydrolase 70 (GH70) family, comprising
      enzymes with a permuted (beta/alpha)8 barrel that use sucrose to synthesize alpha
      D-glucan polymers. The GTFB enzyme reaction and product specificities, however,
      are novel for the GH70 family, resembling those of the GH13 alpha-amylase type of
      enzymes in using maltooligosaccharides as substrates but differing in introducing
      a series of alpha1->6 glycosidic linkages into linear oligosaccharide products.
      We conclude that GTFB represents a novel evolutionary intermediate between the
      GH13 and GH70 enzyme families, and we speculate about its origin.

PMID- 21948834
TI  - Hydrocarbon-degrading bacteria and the bacterial community response in gulf of
      Mexico beach sands impacted by the deepwater horizon oil spill.
AB  - A significant portion of oil from the recent Deepwater Horizon (DH) oil spill in
      the Gulf of Mexico was transported to the shoreline, where it may have severe
      ecological and economic consequences. The objectives of this study were (i) to
      identify and characterize predominant oil-degrading taxa that may be used as
      model hydrocarbon degraders or as microbial indicators of contamination and (ii)
      to characterize the in situ response of indigenous bacterial communities to oil
      contamination in beach ecosystems. This study was conducted at municipal
      Pensacola Beach, FL, where chemical analysis revealed weathered oil petroleum
      hydrocarbon (C8 to C40) concentrations ranging from 3.1 to 4,500 mg kg-1 in beach
      sands. A total of 24 bacterial strains from 14 genera were isolated from oiled
      beach sands and confirmed as oil-degrading microorganisms. Isolated bacterial
      strains were primarily Gammaproteobacteria, including representatives of genera
      with known oil degraders (Alcanivorax, Marinobacter, Pseudomonas, and
      Acinetobacter). Sequence libraries generated from oiled sands revealed phylotypes
      that showed high sequence identity (up to 99%) to rRNA gene sequences from the
      oil-degrading bacterial isolates. The abundance of bacterial SSU rRNA gene
      sequences was ~10-fold higher in oiled (0.44 * 107 to 10.2 * 107 copies g-1)
      versus clean (0.024 * 107 to 1.4 * 107 copies g-1) sand. Community analysis
      revealed a distinct response to oil contamination, and SSU rRNA gene abundance
      derived from the genus Alcanivorax showed the largest increase in relative
      abundance in contaminated samples. We conclude that oil contamination from the DH
      spill had a profound impact on the abundance and community composition of
      indigenous bacteria in Gulf beach sands, and our evidence points to members of
      the Gammaproteobacteria (Alcanivorax, Marinobacter) and Alphaproteobacteria
      (Rhodobacteraceae) as key players in oil degradation there.

PMID- 21948835
TI  - Identification and characterization of leucocyclicin Q, a novel cyclic
      bacteriocin produced by Leuconostoc mesenteroides TK41401.
AB  - The culture supernatant of Leuconostoc mesenteroides TK41401, isolated from
      Japanese pickles, possessed antimicrobial activity against broad range of a
      bacterial genera and particularly strong activity against Bacillus coagulans, the
      major contaminant of pickles. An antimicrobial peptide was purified in three
      chromatographic steps, and its molecular mass was determined to be 6,115.59 Da by
      electrospray ionization time-of-flight mass spectrometry (ESI-TOF MS). The
      primary structure of this peptide was determined by amino acid and DNA
      sequencing, and these analyses revealed that it was translated as a 63-residue
      precursor. This precursor showed high similarity to the precursor of
      lactocyclicin Q, a cyclic bacteriocin produced by Lactococcus sp. strain QU 12.
      The molecular weight calculated after cyclization, which was presumed to involve
      the same process as in lactocyclicin Q (between L3 and W63), agreed with that
      estimated by ESI-TOF MS. This peptide was proved to be a novel cyclic
      bacteriocin, and it was termed leucocyclicin Q. The antimicrobial spectrum of
      this bacteriocin clearly differed from that of lactocyclicin Q, even though their
      primary structures were quite similar. This is the first report of a cyclic
      bacteriocin produced by a strain of the genus Leuconostoc.

PMID- 21948836
TI  - Correlation of genomic and physiological traits of thermoanaerobacter species
      with biofuel yields.
AB  - Thermophilic anaerobic noncellulolytic Thermoanaerobacter species are of great
      biotechnological importance in cellulosic ethanol production due to their ability
      to produce high ethanol yields by simultaneous fermentation of hexose and
      pentose. Understanding the genome structure of these species is critical to
      improving and implementing these bacteria for possible biotechnological use in
      consolidated bioprocessing schemes (CBP) for cellulosic ethanol production. Here
      we describe a comparative genome analysis of two ethanologenic bacteria,
      Thermoanaerobacter sp. X514 and Thermoanaerobacter pseudethanolicus 39E. Compared
      to 39E, X514 has several unique key characteristics important to cellulosic
      biotechnology, including additional alcohol dehydrogenases and xylose
      transporters, modifications to pentose metabolism, and a complete vitamin B12
      biosynthesis pathway. Experimental results from growth, metabolic flux, and
      microarray gene expression analyses support genome sequencing-based predictions
      which help to explain the distinct differences in ethanol production between
      these strains. The availability of whole-genome sequence and comparative genomic
      analyses will aid in engineering and optimizing Thermoanaerobacter strains for
      viable CBP strategies.

PMID- 21948838
TI  - Pulsed-field gel electrophoresis supports the presence of host-adapted Salmonella
      enterica subsp. enterica serovar Typhimurium strains in the British garden bird
      population.
AB  - Salmonellosis is a frequently diagnosed infectious disease of passerine birds in
      garden habitats within Great Britain with potential implications for human and
      domestic animal health. Postmortem examinations were performed on 1,477 garden
      bird carcasses of circa 50 species from England and Wales, 1999 to 2007
      inclusive. Salmonellosis was confirmed in 263 adult birds of 10 passerine species
      in this 11-year longitudinal study. A subset of 124 fully biotyped Salmonella
      enterica subsp. enterica serovar Typhimurium isolates was examined using pulsed
      field gel electrophoresis to investigate the hypothesis that these strains are
      host adapted and to determine whether this molecular technique offers greater
      resolution in understanding the epidemiology of Salmonella Typhimurium infection
      than phage typing alone. For the two most common phage types, definitive type
      (DT) 40 and DT56v, which together accounted for 97% (120/124) of isolates, pulsed
      field gel electrophoresis groupings closely correlated with phage type with
      remarkably few exceptions. A high degree of genetic similarity (>90%) was
      observed within and between the two most common pulsed-field gel electrophoresis
      groups. No clustering or variation was found in the pulsed-field gel
      electrophoresis groupings by bird species, year, or geographical region beyond
      that revealed by phage typing. These findings support the hypothesis that there
      are currently two host-adapted Salmonella phage types, S. Typhimurium DT40 and
      DT56v, circulating widely in British garden birds and that the reservoir of
      infection is maintained within wild bird populations. Large-scale multilocus
      sequence typing studies are required to further investigate the epidemiology of
      this infection.

PMID- 21948837
TI  - Membrane stresses induced by overproduction of free fatty acids in Escherichia
      coli.
AB  - Microbially produced fatty acids are potential precursors to high-energy-density
      biofuels, including alkanes and alkyl ethyl esters, by either catalytic
      conversion of free fatty acids (FFAs) or enzymatic conversion of acyl-acyl
      carrier protein or acyl-coenzyme A intermediates. Metabolic engineering efforts
      aimed at overproducing FFAs in Escherichia coli have achieved less than 30% of
      the maximum theoretical yield on the supplied carbon source. In this work, the
      viability, morphology, transcript levels, and protein levels of a strain of E.
      coli that overproduces medium-chain-length FFAs was compared to an engineered
      control strain. By early stationary phase, an 85% reduction in viable cell counts
      and exacerbated loss of inner membrane integrity were observed in the FFA
      overproducing strain. These effects were enhanced in strains endogenously
      producing FFAs compared to strains exposed to exogenously fed FFAs. Under two
      sets of cultivation conditions, long-chain unsaturated fatty acid content greatly
      increased, and the expression of genes and proteins required for unsaturated
      fatty acid biosynthesis were significantly decreased. Membrane stresses were
      further implicated by increased expression of genes and proteins of the phage
      shock response, the MarA/Rob/SoxS regulon, and the nuo and cyo operons of aerobic
      respiration. Gene deletion studies confirmed the importance of the phage shock
      proteins and Rob for maintaining cell viability; however, little to no change in
      FFA titer was observed after 24 h of cultivation. The results of this study serve
      as a baseline for future targeted attempts to improve FFA yields and titers in E.
      coli.

PMID- 21948839
TI  - Scandium stimulates the production of amylase and bacilysin in Bacillus subtilis.
AB  - We investigated the effects of rare earth elements on enzyme production and
      secondary metabolism in Bacillus subtilis. Addition of scandium to the growth
      medium stimulated the production of both amylase and bacilysin at the
      transcriptional level, thus showing scandium to have a remarkable impact in B.
      subtilis.

PMID- 21948840
TI  - Hemocytes are sites of enteric virus persistence within oysters.
AB  - The goal of this study was to determine how enteric viruses persist within
      shellfish tissues. Several lines of novel evidence show that phagocytic blood
      cells (hemocytes) of Eastern oysters (Crassostrea virginica) play an important
      role in the retention of virus particles. Our results demonstrated an association
      of virus contamination with hemocytes but not with hemolymph. Live oysters
      contaminated overnight with hepatitis A virus (HAV) and murine norovirus (MNV)
      had 56% and 80% of extractable virus associated with hemocytes, respectively.
      Transfer of HAV-contaminated hemocytes to naive (virus-free) oysters resulted in
      naive oyster meat testing HAV positive for up to 3 weeks. Acid tolerance of HAV,
      MNV, poliovirus (PV), and feline calicivirus (FCV) correlated with the ability of
      each virus to persist within oysters. Using reverse transcription-PCR (RT-PCR) to
      evaluate persistence of these viruses in oysters, we showed that HAV persisted
      the longest (>21 days) and was most acid resistant, MNV and PV were less tolerant
      of acidic pH, persisting for up to 12 days and 1 day, respectively, and FCV did
      not persist (<1 day) within oysters and was not acid tolerant. This suggests that
      the ability of a virus to tolerate the acidic conditions typical of
      phagolysosomal vesicles within hemocytes plays a role in determining virus
      persistence in shellfish. Evaluating oyster and hemocyte homogenates and live
      contaminated oysters as a prelude to developing improved viral RNA extraction
      methods, we found that viruses were extracted more expediently from hemocytes
      than from whole shellfish tissues and gave similar RT-PCR detection
      sensitivities.

PMID- 21948842
TI  - One-pot synthesis of diverse DL-configuration dipeptides by a Streptomyces D
      stereospecific amidohydrolase.
AB  - The synthesis of diverse DL-configuration dipeptides in a one-pot reaction was
      demonstrated by using a function of the aminolysis reaction of a D-stereospecific
      amidohydrolase from Streptomyces sp., a clan SE, S12 family peptidase categorized
      as a peptidase with D-stereospecificity. The enzyme was able to use various
      aminoacyl derivatives, including L-aminoacyl derivatives, as acyl donors and
      acceptors. Investigations of the specificity of the peptide synthetic activity
      revealed that the enzyme preferentially used D-aminoacyl derivatives as acyl
      donors. In contrast, L-amino acids and their derivatives were preferentially used
      as acyl acceptors. Consequently, the synthesized dipeptides had a DL
      configuration when D- and L-aminoacyl derivatives were mixed in a one-pot
      reaction. This report also describes that the enzyme produced cyclo(D-Pro-L-Arg),
      a specific inhibitor of family 18 chitinase, with a conversion rate for D-Pro
      benzyl ester and L-Arg methyl ester to cyclo(D-Pro-L-Arg) of greater than 65%.
      Furthermore, based on results of cyclo(D-Pro-L-Arg) synthesis, we propose a
      reaction mechanism for cyclo(D-Pro-L-Arg) production.

PMID- 21948841
TI  - Proteomic and functional analysis of the cellulase system expressed by Postia
      placenta during brown rot of solid wood.
AB  - Brown rot basidiomycetes have an important ecological role in lignocellulose
      recycling and are notable for their rapid degradation of wood polymers via
      oxidative and hydrolytic mechanisms. However, most of these fungi apparently lack
      processive (exo-acting) cellulases, such as cellobiohydrolases, which are
      generally required for efficient cellulolysis. The recent sequencing of the
      Postia placenta genome now permits a proteomic approach to this longstanding
      conundrum. We grew P. placenta on solid aspen wood, extracted proteins from the
      biodegrading substrate, and analyzed tryptic digests by shotgun liquid
      chromatography-tandem mass spectrometry. Comparison of the data with the
      predicted P. placenta proteome revealed the presence of 34 likely glycoside
      hydrolases, but only four of these--two in glycoside hydrolase family 5, one in
      family 10, and one in family 12--have sequences that suggested possible activity
      on cellulose. We expressed these enzymes heterologously and determined that they
      all exhibited endoglucanase activity on phosphoric acid-swollen cellulose. They
      also slowly hydrolyzed filter paper, a more crystalline substrate, but the
      soluble/insoluble reducing sugar ratios they produced classify them as
      nonprocessive. Computer simulations indicated that these enzymes produced
      soluble/insoluble ratios on reduced phosphoric acid-swollen cellulose that were
      higher than expected for random hydrolysis, which suggests that they could
      possess limited exo activity, but they are at best 10-fold less processive than
      cellobiohydrolases. It appears likely that P. placenta employs a combination of
      oxidative mechanisms and endo-acting cellulases to degrade cellulose efficiently
      in the absence of a significant processive component.

PMID- 21948843
TI  - Gamma-butyrolactone regulatory system of Streptomyces chattanoogensis links
      nutrient utilization, metabolism, and development.
AB  - Gamma-butyrolactones (GBLs) produced by several Streptomyces species have been
      shown to serve as quorum-sensing signaling molecules for activating antibiotic
      production. The GBL system of Streptomyces chattanoogensis L10, a producer of
      antifungal agent natamycin, consists of three genes: scgA, scgX, and scgR. Both
      scgA and scgX contribute to GBL production, while scgR encodes a GBL receptor.
      DeltascgA and DeltascgX mutants of S. chattanoogensis behaved identically: they
      had a growth defect in submerged cultures and delayed or abolished the
      morphological differentiation and secondary metabolites production on solid
      medium. ScgR could bind to the promoter region of scgA and repress its
      transcription. Moreover, scgA seems also to be controlled by a GBL-mediated
      negative-feedback system. Hence, it is apparent that GBL biosynthesis is tightly
      controlled to ensure the correct timing for metabolic switch. An additional
      direct ScgR-target gene gbdA was identified by genomic SELEX and transcriptional
      analysis. Comparative proteomic analysis between L10 and its DeltascgA mutant
      revealed that the GBL system affects the expression of more than 50 proteins,
      including enzymes involved in carbon uptake system, primary metabolism, and
      stress response, we thus conclude that scgR-scgA-scgX constitute a novel GBL
      regulatory system involved in nutrient utilization, triggering adaptive
      responses, and finally dictating the switch from primary to secondary metabolism.

PMID- 21948844
TI  - Nostophycin biosynthesis is directed by a hybrid polyketide synthase-nonribosomal
      peptide synthetase in the toxic cyanobacterium Nostoc sp. strain 152.
AB  - Cyanobacteria are a rich source of natural products with interesting
      pharmaceutical properties. Here, we report the identification, sequencing,
      annotation, and biochemical analysis of the nostophycin (npn) biosynthetic gene
      cluster. The npn gene cluster spans 45.1 kb and consists of three open reading
      frames encoding a polyketide synthase, a mixed polyketide nonribosomal peptide
      synthetase, and a nonribosomal peptide synthetase. The genetic architecture and
      catalytic domain organization of the proteins are colinear in arrangement, with
      the putative order of the biosynthetic assembly of the cyclic heptapeptide. NpnB
      contains an embedded monooxygenase domain linking nonribosomal peptide synthetase
      (NRPS) and polyketide synthase (PKS) catalytic domains and predicted here to
      hydroxylate the nostophycin during assembly. Expression of the adenylation
      domains and subsequent substrate specificity assays support the involvement of
      this cluster in nostophycin biosynthesis. Biochemical analyses suggest that the
      loading substrate of NpnA is likely to be a phenylpropanoic acid necessitating
      deletion of a carbon atom to explain the biosynthesis of nostophycin.
      Biosyntheses of nostophycin and microcystin resemble each other, but the
      phylogenetic analyses suggest that they are distantly related to one another.

PMID- 21948845
TI  - Recovery of as-yet-uncultured soil acidobacteria on dilute solid media.
AB  - A growing number of Acidobacteria strains have been isolated from environments
      worldwide, with most isolates derived from acidic samples and affiliated with
      subdivision 1. We recovered 18 Acidobacteria strains from an alkaline soil, among
      which 11 belonged to the previously uncultured subdivision 6. Various medium
      formulations were tested for their effects on Acidobacteria growth.

PMID- 21948846
TI  - Improvement of glyphosate resistance through concurrent mutations in three amino
      acids of the Ochrobactrum 5-enopyruvylshikimate-3-phosphate synthase.
AB  - A mutant of 5-enopyruvylshikimate-3-phosphate synthase from Ochrobactrum anthropi
      was identified after four rounds of DNA shuffling and screening. Its ability to
      restore the growth of the mutant ER2799 cell on an M9 minimal medium containing
      300 mM glyphosate led to its identification. The mutant had mutations in seven
      amino acids: E145G, N163H, N267S, P318R, M377V, M425T, and P438L. Among these
      mutations, N267S, P318R, and M425T have never been previously reported as
      important residues for glyphosate resistance. However, in the present study they
      were found by site-directed mutagenesis to collectively contribute to the
      improvement of glyphosate tolerance. Kinetic analyses of these three mutants
      demonstrated that the effectiveness of these three individual amino acid
      alterations on glyphosate tolerance was in the order P318R > M425T > N267S. The
      results of the kinetic analyses combined with a three-dimensional structure
      modeling of the location of P318R and M425T demonstrate that the lower
      hemisphere's upper surface is possibly another important region for glyphosate
      resistance. Furthermore, the transgenic Arabidopsis was obtained to confirm the
      potential of the mutant in developing glyphosate-resistant crops.

PMID- 21948848
TI  - Leaching of Cryptosporidium parvum oocysts, Escherichia coli, and a Salmonella
      enterica serovar Typhimurium bacteriophage through intact soil cores following
      surface application and injection of slurry.
AB  - Increasing amounts of livestock manure are being applied to agricultural soil,
      but it is unknown to what extent this may be associated with contamination of
      aquatic recipients and groundwater if microorganisms are transported through the
      soil under natural weather conditions. The objective of this study was therefore
      to evaluate how injection and surface application of pig slurry on intact sandy
      clay loam soil cores influenced the leaching of Salmonella enterica serovar
      Typhimurium bacteriophage 28B, Escherichia coli, and Cryptosporidium parvum
      oocysts. All three microbial tracers were detected in the leachate on day 1, and
      the highest relative concentration was detected on the fourth day (0.1 pore
      volume). Although the concentration of the phage 28B declined over time, the
      phage was still found in leachate at day 148. C. parvum oocysts and chloride had
      an additional rise in the relative concentration at a 0.5 pore volume,
      corresponding to the exchange of the total pore volume. The leaching of E. coli
      was delayed compared with that of the added microbial tracers, indicating a
      stronger attachment to slurry particles, but E. coli could be detected up to 3
      months. Significantly enhanced leaching of phage 28B and oocysts by the injection
      method was seen, whereas leaching of the indigenous E. coli was not affected by
      the application method. Preferential flow was the primary transport vehicle, and
      the diameter of the fractures in the intact soil cores facilitated transport of
      all sizes of microbial tracers under natural weather conditions.

PMID- 21948847
TI  - Influence of host phylogeographic patterns and incomplete lineage sorting on
      within-species genetic variability in Wigglesworthia species, obligate symbionts
      of tsetse flies.
AB  - Vertical transmission of obligate symbionts generates a predictable evolutionary
      history of symbionts that reflects that of their hosts. In insects, evolutionary
      associations between symbionts and their hosts have been investigated primarily
      among species, leaving population-level processes largely unknown. In this study,
      we investigated the tsetse (Diptera: Glossinidae) bacterial symbiont,
      Wigglesworthia glossinidia, to determine whether observed codiversification of
      symbiont and tsetse host species extends to a single host species (Glossina
      fuscipes fuscipes) in Uganda. To explore symbiont genetic variation in G. f.
      fuscipes populations, we screened two variable loci (lon and lepA) from the
      Wigglesworthia glossinidia bacterium in the host species Glossina fuscipes
      fuscipes (W. g. fuscipes) and examined phylogeographic and demographic
      characteristics in multiple host populations. Symbiont genetic variation was
      apparent within and among populations. We identified two distinct symbiont
      lineages, in northern and southern Uganda. Incongruence length difference (ILD)
      tests indicated that the two lineages corresponded exactly to northern and
      southern G. f. fuscipes mitochondrial DNA (mtDNA) haplogroups (P = 1.0). Analysis
      of molecular variance (AMOVA) confirmed that most variation was partitioned
      between the northern and southern lineages defined by host mtDNA (85.44%).
      However, ILD tests rejected finer-scale congruence within the northern and
      southern populations (P = 0.009). This incongruence was potentially due to
      incomplete lineage sorting that resulted in novel combinations of symbiont
      genetic variants and host background. Identifying these novel combinations may
      have public health significance, since tsetse is the sole vector of sleeping
      sickness and Wigglesworthia is known to influence host vector competence. Thus,
      understanding the adaptive value of these host-symbiont combinations may afford
      opportunities to develop vector control methods.

PMID- 21948850
TI  - Evolutionary story of mammalian-specific amelogenin exons 4, "4b", 8, and 9.
AB  - Amelogenin gene organization varies from 6 exons (1,2,3,5,6,7) in amphibians and
      sauropsids to 10 in rodents. The additional exons are exons 4, 8, 9, and "4b",
      the latter being as yet unidentified in AMELX transcripts. To learn more about
      the evolutionary origin of these exons, we used an in silico approach to find
      them in 39 tetrapod genomes. AMEL organization with 6 exons was the ancestral
      condition. Exon 4 was created in an ancestral therian (marsupials + placentals),
      then exon 9 in an ancestral placental, and finally exons "4b" and 8 in rodents,
      after divergence of the squirrel lineage. These exons were either inactivated in
      some lineages or remained functional: Exon 4 is functional from artiodactyls
      onward; exon 9 is known, to date, only in rodents, but could be coding in various
      mammals; and exon "4b" was probably coding in some rodents. We performed PCR of
      cDNA isolated from mouse and human tooth buds to identify the presence of these
      transcripts. A sequence analogous to exon "4b", and to exon 9, could not be
      amplified from the respective tooth cDNA, indicating that even though sequences
      similar to these exons are present, they are not transcribed in these species.

PMID- 21948849
TI  - Cloning-independent and counterselectable markerless mutagenesis system in
      Streptococcus mutans.
AB  - Insertion duplication mutagenesis and allelic replacement mutagenesis are among
      the most commonly utilized approaches for targeted mutagenesis in bacteria.
      However, both techniques are limited by a variety of factors that can complicate
      mutant phenotypic studies. To circumvent these limitations, multiple markerless
      mutagenesis techniques have been developed that utilize either temperature
      sensitive plasmids or counterselectable suicide vectors containing both positive-
      and negative-selection markers. For many species, these techniques are not
      especially useful due to difficulties of cloning with Escherichia coli and/or a
      lack of functional negative-selection markers. In this study, we describe the
      development of a novel approach for the creation of markerless mutations. This
      system employs a cloning-independent methodology and should be easily adaptable
      to a wide array of Gram-positive and Gram-negative bacterial species. The entire
      process of creating both the counterselection cassette and mutation constructs
      can be completed using overlapping PCR protocols, which allows extremely quick
      assembly and eliminates the requirement for either temperature-sensitive
      replicons or suicide vectors. As a proof of principle, we used Streptococcus
      mutans reference strain UA159 to create markerless in-frame deletions of 3
      separate bacteriocin genes as well as triple mutants containing all 3 deletions.
      Using a panel of 5 separate wild-type S. mutans strains, we further demonstrated
      that the procedure is nearly 100% efficient at generating clones with the desired
      markerless mutation, which is a considerable improvement in yield compared to
      existing approaches.

PMID- 21948851
TI  - Nuclear magnetic resonance: a tool for imaging belowground damage caused by
      Heterodera schachtii and Rhizoctonia solani on sugar beet.
AB  - Belowground symptoms of sugar beet caused by the beet cyst nematode (BCN)
      Heterodera schachtii include the development of compensatory secondary roots and
      beet deformity, which, thus far, could only be assessed by destructively removing
      the entire root systems from the soil. Similarly, the symptoms of Rhizoctonia
      crown and root rot (RCRR) caused by infections of the soil-borne basidiomycete
      Rhizoctonia solani require the same invasive approach for identification. Here
      nuclear magnetic resonance imaging (MRI) was used for the non-invasive detection
      of belowground symptoms caused by BCN and/or RCRR on sugar beet. Excessive
      lateral root development and beet deformation of plants infected by BCN was
      obvious 28 days after inoculation (dai) on MRI images when compared with non
      infected plants. Three-dimensional images recorded at 56 dai showed BCN cysts
      attached to the roots in the soil. RCRR was visualized by a lower intensity of
      the MRI signal at sites where rotting occurred. The disease complex of both
      organisms together resulted in RCRR development at the site of nematode
      penetration. Damage analysis of sugar beet plants inoculated with both pathogens
      indicated a synergistic relationship, which may result from direct and indirect
      interactions. Nuclear MRI of plants may provide valuable, new insight into the
      development of pathogens infecting plants below- and aboveground because of its
      non-destructive nature and the sufficiently high spatial resolution of the
      method.

PMID- 21948852
TI  - Silver ions disrupt K+ homeostasis and cellular integrity in intact barley
      (Hordeum vulgare L.) roots.
AB  - The heavy metals silver, gold, and mercury can strongly inhibit aquaporin
      mediated water flow across plant cell membranes, but critical examinations of
      their side effects are rare. Here, the short-lived radiotracer (42)K is used to
      demonstrate that these metals, especially silver, profoundly change potassium
      homeostasis in roots of intact barley (Hordeum vulgare L.) plants, by altering
      unidirectional K(+) fluxes. Doses as low as 5 MUM AgNO(3) rapidly reduced K(+)
      influx to 5% that of controls, and brought about pronounced and immediate
      increases in K(+) efflux, while higher doses of Au(3+) and Hg(2+) were required
      to produce similar responses. Reduced influx and enhanced efflux of K(+) resulted
      in a net loss of >40% of root tissue K(+) during a 15 min application of 500 MUM
      AgNO(3), comprising the entire cytosolic potassium pool and about a third of the
      vacuolar pool. Silver also brought about major losses of UV-absorbing compounds,
      total electrolytes, and NH(4)(+). Co-application, with silver, of the channel
      blockers Cs(+), TEA(+), or Ca(2+), did not affect the enhanced efflux, ruling out
      the involvement of outwardly rectifying ion channels. Taken together with an
      examination of propidium iodide staining under confocal microscopy, the results
      indicate that silver ions affect K(+) homeostasis by directly inhibiting K(+)
      influx at lower concentrations, and indirectly inhibiting K(+) influx and
      enhancing K(+) efflux, via membrane destruction, at higher concentrations.
      Ni(2+), Cd(2+), and Pb(2+), three heavy metals not generally known to affect
      aquaporins, did not enhance K(+) efflux or cause propidium iodide incorporation.
      The study reveals strong and previously unknown effects of major aquaporin
      inhibitors and recommends caution in their application.

PMID- 21948853
TI  - Chaperone-like properties of tobacco plastid thioredoxins f and m.
AB  - Thioredoxins (Trxs) are ubiquitous disulphide reductases that play important
      roles in the redox regulation of many cellular processes. However, some redox
      independent functions, such as chaperone activity, have also been attributed to
      Trxs in recent years. The focus of our study is on the putative chaperone
      function of the well-described plastid Trxs f and m. To that end, the cDNA of
      both Trxs, designated as NtTrxf and NtTrxm, was isolated from Nicotiana tabacum
      plants. It was found that bacterially expressed tobacco Trx f and Trx m, in
      addition to their disulphide reductase activity, possessed chaperone-like
      properties. In vitro, Trx f and Trx m could both facilitate the reactivation of
      the cysteine-free form of chemically denatured glucose-6 phosphate dehydrogenase
      (foldase chaperone activity) and prevent heat-induced malate dehydrogenase
      aggregation (holdase chaperone activity). Our results led us to infer that the
      disulphide reductase and foldase chaperone functions prevail when the proteins
      occur as monomers and the well-conserved non-active cysteine present in Trx f is
      critical for both functions. By contrast, the holdase chaperone activity of both
      Trxs depended on their oligomeric status: the proteins were functional only when
      they were associated with high molecular mass protein complexes. Because the
      oligomeric status of both Trxs was induced by salt and temperature, our data
      suggest that plastid Trxs could operate as molecular holdase chaperones upon
      oxidative stress, acting as a type of small stress protein.

PMID- 21948854
TI  - The impact of environmental experiences on symptoms of anxiety and depression
      across the life span.
AB  - Symptoms of anxiety and depression are relatively stable over time. Can this
      stability be explained by genetic influences, or is it caused by the long-lasting
      effects of accumulating environmental experiences? To address this question, we
      analyzed longitudinally assessed symptoms of anxiety and depression in eight
      samples of monozygotic twins of widely varying ages. These samples were drawn
      from American and European population-based registries. Using hierarchical linear
      modeling, we examined individual differences and individual changes in the level
      of symptoms over time. This method enabled us to decompose the variance into the
      predictable variance shared by both members of each pair of twins, the
      differences between individuals within pairs, and the residual variance. We then
      modeled how these components of individual variation changed over time. Within
      pairs, the twins' predicted levels of symptoms increasingly diverged from
      childhood until late adulthood, at which point the divergence ceased. By middle
      adulthood, environmental experiences contributed substantially to stable and
      predictable interindividual differences in levels of anxiety and depression.

PMID- 21948855
TI  - Economic inequality is linked to biased self-perception.
AB  - People's self-perception biases often lead them to see themselves as better than
      the average person (a phenomenon known as self-enhancement). This bias varies
      across cultures, and variations are typically explained using cultural variables,
      such as individualism versus collectivism. We propose that socioeconomic
      differences among societies--specifically, relative levels of economic inequality
      -play an important but unrecognized role in how people evaluate themselves.
      Evidence for self-enhancement was found in 15 diverse nations, but the magnitude
      of the bias varied. Greater self-enhancement was found in societies with more
      income inequality, and income inequality predicted cross-cultural differences in
      self-enhancement better than did individualism/collectivism. These results
      indicate that macrosocial differences in the distribution of economic goods are
      linked to microsocial processes of perceiving the self.

PMID- 21948856
TI  - The effect of limited English proficiency on falls risk and falls prevention
      after stroke.

PMID- 21948857
TI  - Association between the Geriatric Giants of urinary incontinence and falls in
      older people using data from the Leicestershire MRC Incontinence Study.
AB  - OBJECTIVE: To determine whether urinary incontinence per se and different types
      of urinary incontinence individually are associated with an increased risk of
      falls in those aged 70 years and over. To investigate whether the presence of
      urinary symptoms, poor quality of life and physical limitations in this
      population with urinary incontinence is associated with falls. DESIGN: Study
      using data from the cross-sectional postal questionnaire undertaken in the
      Leicestershire Medical Research Council Incontinence Study. SETTING:
      Leicestershire. PARTICIPANTS: A total of 5,474 people aged 70 years or more
      living in the community randomly selected from general practitioners' lists.
      RESULTS: Urinary incontinence and both urge and stress incontinence were
      positively related to falls (P < 0.0001, P < 0.001 and P = 0.007, respectively).
      The larger the volume of urine lost, the greater the risk of falls (P < 0.0001).
      Falls were associated with the presence of urinary symptoms (P = 0.01 or less),
      physical limitations (P = 0.001 or less) and having a poorer quality of life (P =
      0.004 or less) in respondents with urinary incontinence. CONCLUSIONS: An
      association has been shown between falling and urinary leakage including the
      previously unreported association with stress leakage. Falling and urinary
      incontinence were found to be associated with physical limitations and had an
      impact on quality of life.

PMID- 21948858
TI  - Effects of reboxetine and citalopram on appraisal of infant facial expressions
      and attentional biases.
AB  - Difficulties in mother-child interaction are commonly observed in the context of
      postnatal depression. These difficulties may result in part from the negative
      cognitive bias present in depression, which may in turn lead to biased negative
      perceptions of the infant: in particular, these biases encompass the negative
      appraisal of facial expressions. Given the important role of early mother-child
      interactions in child development it is vital to investigate potential
      interventions that might be beneficial in ameliorating the negative cognitive
      bias. This study aimed to examine the effects of two different antidepressants
      (reboxetine and citalopram) on the appraisal of infant facial expressions of
      emotion using a faces rating task, and on attention to infant emotion using an
      attentional probe. Thirty-nine volunteers were randomly assigned to a double
      blind 7-day intervention with either placebo, citalopram or reboxetine. There
      were significant positive effects on the appraisal of facial expressions;
      participants assigned to the placebo group rated positive faces less positively
      than those either in the citalopram or in the reboxetine groups. However, there
      was no evidence that these drugs had an effect on attentional vigilance. If
      antidepressants are able to help a mother to perceive her infant's facial
      expressions as more positive, this may lead to more positive interactions,
      thereby potentially mitigating the negative effects of depression on infant
      development. These findings should be treated with caution until replicated in
      larger and clinical samples.

PMID- 21948859
TI  - Benefit of cyclophosphamide therapy in IgA nephritis may have been obscured by
      warfarin-related nephropathy in the randomized trials in which warfarin and
      dipyridamole were used in combination with cyclophosphamide.

PMID- 21948860
TI  - Applicability of solid-phase cytometry and epifluorescence microscopy for rapid
      assessment of the microbiological quality of dialysis water.
AB  - BACKGROUND: Currently, the gold standard to assess the microbiological quality of
      dialysis water is the determination of heterotrophic plate counts (HPC). The long
      waiting time of the HPC method and the fact that most bacteria are not culturable
      on agar plates provokes the search for rapid alternative methods for monitoring
      the microbiological quality of dialysis water. METHODS: We tested the
      applicability of total viable counts (TVC) and total direct counts (TDC),
      determined via solid-phase cytometry and epifluorescence microscopy (EFM), in
      comparison to the standard HPC determination method in 113 samples from 13
      dialysis water treatment units (59 drinking water and 54 dialysis water samples).
      Additionally, for a set of dialysis water samples (n = 22) endotoxin
      concentrations were also determined. RESULTS: TVC showed high correlation with
      HPC and results were of comparable magnitude for most investigated dialysis water
      samples [median: 3 cells/colony forming units (CFU) 100 mL(-1)]. However, in one
      dialysis water sample, HPC values (5800 CFU 100 mL(-1)) were >35-fold lower than
      TVC values (2.05 * 10(5) cells 100 mL(-1)) indicating severe limits of the HPC
      method to assess the microbiological quality of dialysis water. For drinking
      water, TVC (median: 4.8 * 10(4) cells 100 mL(-1)) was on average one order of
      magnitude higher than HPC (median: 2.5 * 10(3) cells 100 mL(-1)). TDCs (median
      dialysis water: 1.1 * 10(4) cells 100 mL(-1) and median drinking water: 4.9 *
      10(6) cells 100 mL(-1)) were always several orders of magnitude higher than HPC
      or TVC. CONCLUSIONS: We propose that the TVC/solid-phase cytometry approach is a
      reliable and rapid alternative to the culture-dependent approach for assessment
      of the microbiological quality of dialysis water, especially when fast results
      are needed. TDC determined via EFM lacks sensitivity and reliability for
      assessing microbial concentrations in low-cell dialysis water samples since the
      limits of detection and quantification are high.

PMID- 21948861
TI  - PLA2 receptor autoantibodies, complement activation and podocyte damage.

PMID- 21948862
TI  - Usefulness of waist circumference as a marker of abdominal adiposity in
      peritoneal dialysis: a cross-sectional and prospective analysis.
AB  - BACKGROUND: Waist circumference (WC) has been well recognized as a surrogate
      marker of abdominal adiposity. In peritoneal dialysis (PD) patients, however,
      aspects related to this dialysis modality, such as abdominal distension, presence
      of catheter and frequent hernia, raise questions regarding the reliability of WC
      measurements. Herein, we investigated for the first time whether WC is a reliable
      marker of abdominal adiposity in PD population. METHODS: This study included 107
      prevalent PD patients [56% male, age 52 +/- 17 years, 35% diabetics, body mass
      index (BMI) 24.8 +/- 3.9 kg/m(2)]. WC measured at umbilicus level was evaluated
      against the trunk fat assessed by dual-energy x-ray absorptiometry at baseline
      and after 6 months. All measurements were taken with the empty abdominal cavity.
      RESULTS: At baseline, a strong correlation of WC with trunk fat (r = 0.81; P <
      0.001) was observed. Adjusting for gender, age, dialysis vintage and BMI, WC was
      independently associated with trunk fat (beta = 0.30; P < 0.001; R(2) = 0.77).
      The agreement between WC and trunk fat was 0.59 (kappa statistic) and the area
      under the curve was 0.90. In the prospective evaluation, we observed that changes
      in WC correlated with changes in trunk fat as well (r = 0.49; P < 0.001). The
      kappa statistic of 0.48 remained indicative of a moderate agreement between the
      methods. The receiver operating characteristic curve analysis showed that WC was
      sensitive to detect changes in trunk fat (area under the curve 0.76). In the
      logistic regression analysis adjusting for gender, age and BMI, changes in WC
      were independently associated with changes in trunk fat. CONCLUSION: The simple
      anthropometric method of WC is a reliable marker of abdominal adiposity in PD
      patients.

PMID- 21948864
TI  - Reviewing our book reviews: fifty years and counting.

PMID- 21948863
TI  - Carotenoid accumulation in orange-pigmented Capsicum annuum fruit, regulated at
      multiple levels.
AB  - The pericarp of Capsicum fruit is a rich dietary source of carotenoids.
      Accumulation of these compounds may be controlled, in part, by gene transcription
      of biosynthetic enzymes. The carotenoid composition in a number of orange
      coloured C. annuum cultivars was determined using HPLC and compared with
      transcript abundances for four carotenogenic enzymes, Psy, LcyB, CrtZ-2, and Ccs
      determined by qRT-PCR. There were unique carotenoid profiles as well as distinct
      patterns of transcription of carotenogenic enzymes within the seven orange
      coloured cultivars. In one cultivar, 'Fogo', carrying the mutant ccs-3 allele,
      transcripts were detected for this gene, but no CCS protein accumulated. The
      premature stop termination in ccs-3 prevented expression of the biosynthetic
      activity to synthesize the capsanthin and capsorubin forms of carotenoids. In two
      other orange-coloured cultivars, 'Orange Grande' and 'Oriole', both with wild
      type versions of all four carotenogenic enzymes, no transcripts for Ccs were
      detected and no red pigments accumulated. Finally, in a third case, the orange
      coloured cultivar, Canary, transcripts for all four of the wild-type
      carotenogenic enzymes were readily detected yet no CCS protein appeared to
      accumulate and no red carotenoids were synthesized. In the past, mutations in Psy
      and Ccs have been identified as the loci controlling colour in the fruit. Now
      there is evidence that a non-structural gene may control colour development in
      Capsicum.

PMID- 21948865
TI  - Aging in Australia.

PMID- 21948866
TI  - Dietary ligands of the aryl hydrocarbon receptor induce anti-inflammatory and
      immunoregulatory effects on murine dendritic cells.
AB  - Activation of the aryl hydrocarbon receptor (AhR) in immune cells, such as
      dendritic cells (DCs), can lead to suppressed immune responses. Although AhR
      activation is most recognized for mediating the effects of its prototypical
      ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), many compounds existing in
      dietary sources can also bind the AhR. Because the immunomodulatory effects of
      indole-3-carbinol (I3C) and indirubin-3'-oxime (IO) have yet to be investigated
      in DCs, we evaluated the potential immunomodulatory effects of these compounds on
      murine DCs. We hypothesized that I3C and IO suppress immune and inflammatory
      responses in DCs. We found that both I3C and IO decreased the expression of
      CD11c, CD40, and CD54 while they increased expression of MHC2 and CD80. Following
      lipopolysaccharide (LPS)-activation, I3C and IO suppressed the production of pro
      inflammatory mediators including tumor necrosis factor-alpha, interleukin (IL)
      1beta, IL-6, IL-12, and nitric oxide but increased IL-10 levels. These effects of
      I3C and IO were partially mediated by the AhR. Additionally, immunoregulatory
      genes, such as ALDH1A, IDO and TGFB, were upregulated following treatment with
      I3C or IO. Both I3C and IO decreased basal levels of nuclear factor-kappa B p65,
      but only I3C suppressed the LPS-induced activity of RelB. Finally, when cultured
      with naive T cells, bone marrow-derived dendritic cells treated with the dietary
      AhR ligands increased the frequency of Foxp3+ Tregs in an antigen-specific
      manner. Taken together, these results indicate that I3C and IO exhibit
      immunosuppressive and anti-inflammatory effects on DCs. Because I3C and IO are
      significantly less toxic than TCDD, these natural products may ultimately become
      useful therapeutics for the treatment of autoimmune and inflammatory diseases.

PMID- 21948868
TI  - Accelerating the development of 21st-century toxicology: outcome of a Human
      Toxicology Project Consortium workshop.
AB  - The U.S. National Research Council (NRC) report on "Toxicity Testing in the 21st
      century" calls for a fundamental shift in the way that chemicals are tested for
      human health effects and evaluated in risk assessments. The new approach would
      move toward in vitro methods, typically using human cells in a high-throughput
      context. The in vitro methods would be designed to detect significant
      perturbations to "toxicity pathways," i.e., key biological pathways that, when
      sufficiently perturbed, lead to adverse health outcomes. To explore progress on
      the report's implementation, the Human Toxicology Project Consortium hosted a
      workshop on 9-10 November 2010 in Washington, DC. The Consortium is a coalition
      of several corporations, a research institute, and a non-governmental
      organization dedicated to accelerating the implementation of 21st-century
      Toxicology as aligned with the NRC vision. The goal of the workshop was to
      identify practical and scientific ways to accelerate implementation of the NRC
      vision. The workshop format consisted of plenary presentations, breakout group
      discussions, and concluding commentaries. The program faculty was drawn from
      industry, academia, government, and public interest organizations. Most
      presentations summarized ongoing efforts to modernize toxicology testing and
      approaches, each with some overlap with the NRC vision. In light of these
      efforts, the workshop identified recommendations for accelerating implementation
      of the NRC vision, including greater strategic coordination and planning across
      projects (facilitated by a steering group), the development of projects that test
      the proof of concept for implementation of the NRC vision, and greater outreach
      and communication across stakeholder communities.

PMID- 21948867
TI  - Activation of the aryl hydrocarbon receptor by TCDD inhibits mammary tumor
      metastasis in a syngeneic mouse model of breast cancer.
AB  - Treatment with aryl hydrocarbon receptor (AhR) agonists can slow or reverse the
      growth of primary mammary tumors in rodents, which has fostered interest in
      developing selective AhR modulators for treatment of breast cancer. However, the
      major goal of breast cancer therapy is to inhibit metastasis, the primary cause
      of mortality in women with this disease. Studies conducted using breast cancer
      cell lines have demonstrated that AhR agonists suppress proliferation,
      invasiveness, and colony formation in vitro; however, further exploration using
      in vivo models of metastasis is warranted. To test the effect of AhR activation
      on metastasis, 4T1.2 mammary tumor cells were injected into the mammary gland fat
      pad of syngeneic Balb/c mice treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD). Primary tumor growth was monitored for 4 weeks, at which time metastasis
      was determined. TCDD treatment suppressed metastasis by approximately 50%, as
      measured both in the lung and in mammary glands at sites distant from the primary
      tumor. Primary tumor growth was not suppressed by TCDD exposure nor was
      proliferation of 4T1.2 cells affected by TCDD treatment in vitro. Taken together,
      these results suggest that the protective effect of AhR activation was selective
      for the metastatic process and not simply the result of a direct decrease in
      tumor cell proliferation or survival at the primary site. These observations in
      immunologically intact animals warrant further investigation into the mechanism
      of the protective effects of AhR activation and support the promise for use of
      AhR modulators to treat breast cancer.

PMID- 21948869
TI  - Integration of dosimetry, exposure, and high-throughput screening data in
      chemical toxicity assessment.
AB  - High-throughput in vitro toxicity screening can provide an efficient way to
      identify potential biological targets for chemicals. However, relying on nominal
      assay concentrations may misrepresent potential in vivo effects of these
      chemicals due to differences in bioavailability, clearance, and exposure. Hepatic
      metabolic clearance and plasma protein binding were experimentally measured for
      239 ToxCast Phase I chemicals. The experimental data were used in a population
      based in vitro-to-in vivo extrapolation model to estimate the daily human oral
      dose, called the oral equivalent dose, necessary to produce steady-state in vivo
      blood concentrations equivalent to in vitro AC(50) (concentration at 50% of
      maximum activity) or lowest effective concentration values across more than 500
      in vitro assays. The estimated steady-state oral equivalent doses associated with
      the in vitro assays were compared with chronic aggregate human oral exposure
      estimates to assess whether in vitro bioactivity would be expected at the dose
      equivalent level of human exposure. A total of 18 (9.9%) chemicals for which
      human oral exposure estimates were available had oral equivalent doses at levels
      equal to or less than the highest estimated U.S. population exposures. Ranking
      the chemicals by nominal assay concentrations would have resulted in different
      chemicals being prioritized. The in vitro assay endpoints with oral equivalent
      doses lower than the human exposure estimates included cell growth kinetics,
      cytokine and cytochrome P450 expression, and cytochrome P450 inhibition. The
      incorporation of dosimetry and exposure provide necessary context for
      interpretation of in vitro toxicity screening data and are important
      considerations in determining chemical testing priorities.

PMID- 21948870
TI  - Delayed reduction of hippocampal synaptic transmission and spines following
      exposure to repeated subclinical doses of organophosphorus pesticide in adult
      mice.
AB  - Agricultural and household organophosphorus (OP) pesticides inhibit
      acetylcholinesterase (AchE), resulting in increased acetylcholine (Ach) in the
      central nervous system. In adults, acute and prolonged exposure to high doses of
      AchE inhibitors causes severe, clinically apparent symptoms, followed by lasting
      memory impairments and cognitive dysfunction. The neurotoxicity of repeated
      environmental exposure to lower, subclinical doses of OP pesticides in adults is
      not as well studied. However, repeated exposure to acetylcholinesterase
      inhibitors, such as chlorpyrifos (CPF), pyridostigmine, and sarin nerve agent,
      has been epidemiologically linked to delayed onset symptoms in Gulf War Illness
      and may be relevant to environmental exposure in farm workers among others. We
      treated adult mice with a subclinical dose (5 mg/kg) of CPF for 5 consecutive
      days and investigated hippocampal synaptic transmission and spine density early
      (2-7 days) and late (3 months) after CPF administration. No signs of cholinergic
      toxicity were observed at any time during or after treatment. At 2-7 days after
      the last injection, we found increased synaptic transmission in the CA3-CA1
      region of the hippocampus of CPF-treated mice compared with controls. In
      contrast, at 3 months after CPF administration, we observed a 50% reduction in
      synaptic transmission likely due to a corresponding 50% decrease in CA1 pyramidal
      neuron synaptic spine density. This study is the first to identify a biphasic
      progression of synaptic abnormalities following repeated OP exposure and suggests
      that even in the absence of acute cholinergic toxicity, repeated exposure to CPF
      causes delayed persistent damage to the adult brain in vivo.

PMID- 21948871
TI  - ZG16p, an animal homolog of beta-prism fold plant lectins, interacts with heparan
      sulfate proteoglycans in pancreatic zymogen granules.
AB  - ZG16p is a soluble 16 kDa pancreatic protein having structural similarities with
      plant beta-prism fold lectins such as the banana lectin BanLec and the jackfruit
      lectin jacalin. ZG16p is postulated to be involved in the formation of zymogen
      granules by interacting with proteoglycans (PGs) localized in pancreatic exocrine
      granule membranes, but direct evidence was lacking. We characterized the
      structural properties of rat pancreatic zymogen granule PGs and examined their
      interaction with ZG16p. Structural analysis of the glycosaminoglycans (GAGs)
      showed that rat pancreatic zymogen granule PGs have heparan sulfate chains with a
      unique property, a high degree of sulfation (DeltaUA-GlcNAc:DeltaUA-GlcNS:DeltaUA
      GlcNAc6S:DeltaUA-GlcNS6S:DeltaUA2S-GlcNS:DeltaUA2S-GlcNS6S,
      27.9:16.6:5.7:22.5:6.2:21.1). After heparin lyase II digestion, the core proteins
      derived from the PGs were detected at molecular weights of 66,000 and 35,000
      40,000. An overlay binding assay revealed that ZG16p binds specifically to
      heparan sulfate PGs by recognizing their GAG chains. Affinity chromatography
      demonstrated that ZG16p binds most strongly to heparin among the zymogen granule
      proteins. Site-directed mutational analysis revealed that the basic amino acid
      residues located in two putative carbohydrate-binding sites (CBSs) of ZG16p,
      which were found in association with the crystal structure of BanLec, are
      responsible for the recognition of heparin. These observations suggest that ZG16p
      is the primary binding partner of the granule heparan sulfate PGs. ZG16p may
      cross-link the granule heparan sulfate chains via two CBSs and facilitate the
      formation of a submembranous matrix, a sorting platform for enzyme proteins on
      the luminal side of the zymogen granule membrane.

PMID- 21948872
TI  - Beta blockers for heart failure with reduced ejection fraction.

PMID- 21948874
TI  - Blood donation in men who have sex with men.

PMID- 21948873
TI  - Impact of CONSORT extension for cluster randomised trials on quality of reporting
      and study methodology: review of random sample of 300 trials, 2000-8.
AB  - OBJECTIVE: To assess the impact of the 2004 extension of the CONSORT guidelines
      on the reporting and methodological quality of cluster randomised trials. DESIGN:
      Methodological review of 300 randomly sampled cluster randomised trials. Two
      reviewers independently abstracted 14 criteria related to quality of reporting
      and four methodological criteria specific to cluster randomised trials. We
      compared manuscripts published before CONSORT (2000-4) with those published after
      CONSORT (2005-8). We also investigated differences by journal impact factor, type
      of journal, and trial setting. DATA SOURCES: A validated Medline search strategy.
      Eligibility criteria for selecting studies Cluster randomised trials published in
      English language journals, 2000-8. RESULTS: There were significant improvements
      in five of 14 reporting criteria: identification as cluster randomised;
      justification for cluster randomisation; reporting whether outcome assessments
      were blind; reporting the number of clusters randomised; and reporting the number
      of clusters lost to follow-up. No significant improvements were found in
      adherence to methodological criteria. Trials conducted in clinical rather than
      non-clinical settings and studies published in medical journals with higher
      impact factor or general medical journals were more likely to adhere to
      recommended reporting and methodological criteria overall, but there was no
      evidence that improvements after publication of the CONSORT extension for cluster
      trials were more likely in trials conducted in clinical settings nor in trials
      published in either general medical journals or in higher impact factor journals.
      CONCLUSION: The quality of reporting of cluster randomised trials improved in
      only a few aspects since the publication of the extension of CONSORT for cluster
      randomised trials, and no improvements at all were observed in essential
      methodological features. Overall, the adherence to reporting and methodological
      guidelines for cluster randomised trials remains suboptimal, and further efforts
      are needed to improve both reporting and methodology.

PMID- 21948875
TI  - Onus is on doctors to encourage patients to have the flu jab.

PMID- 21948876
TI  - Study linking chronic fatigue syndrome with retrovirus is partially retracted.

PMID- 21948878
TI  - Moorfields Eye Hospital is to host European trial of human embryonic stem cells.

PMID- 21948877
TI  - Obama proposes "saving" $320bn from Medicare and Medicaid.

PMID- 21948879
TI  - Government announces end of NHS IT programme--for second time.

PMID- 21948880
TI  - Trusts deny health secretary's claims that private finance initiatives have
      caused major financial problems.

PMID- 21948881
TI  - Better commissioning is needed to deal with combined effects of physical and
      mental illnesses.

PMID- 21948882
TI  - NHS medical director stopped laparoscopic cholecystectomy at Stafford Hospital
      after tip off.

PMID- 21948883
TI  - Case against Christian GP is adjourned to try to persuade patient to give
      evidence.

PMID- 21948884
TI  - Size restrictions on commissioning groups are eroding GPs' engagement.

PMID- 21948885
TI  - Sepsis-associated encephalopathy: review of the neuropsychiatric manifestations
      and cognitive outcome.

PMID- 21948886
TI  - Psychopharmacological neuroprotection in neurodegenerative diseases, part III:
      criteria-based assessment: a report of the ANPA committee on research.
AB  - Neuroprotective therapies for neurodegenerative diseases (NDDs) have proven
      elusive. The established psychotropic agents commonly used to treat the
      neuropsychiatric manifestations of NDDs are potential neuroprotective therapies,
      and neuropsychiatrists and others may benefit from a knowledge of the
      neuroprotective properties of these medications. This report identifies FDA
      approved, first-line psychotropic drugs affecting intracellular mechanisms and
      meriting disease-modifying clinical trials in NDDs. The authors evaluated
      evidence for neuroprotection according to 1) preclinical; and 2) clinical
      criteria. Despite low-to-moderate preclinical evidence scores and scant clinical
      evidence, the most promising investigative priorities are 1) lithium and
      paroxetine in Alzheimer's disease (AD); 2) lithium in tauopathies (frontotemporal
      lobar degeneration [FTLD], FTDP-17); 3) lithium-plus-valproate in AD and
      amyotrophic lateral sclerosis; 4) pramipexole and valproate in Parkinson's
      disease; 5) amantadine and buspirone in multiple system atrophy; and 6)
      antidepressants in Huntington's disease. Preliminary clinical results signal
      caution regarding olanzapine use in AD and poor tolerability of lithium in
      progressive supranuclear palsy and corticobasal degeneration. These preliminary
      findings can lead to further clinical drug trials on the use of these well-known
      medications, not only for their psychotropic effects, but also for
      neuroprotection in NDDs.

PMID- 21948887
TI  - Pathogenic mechanisms of depression in multiple sclerosis.
AB  - Patients with multiple sclerosis (MS) have an increased risk of developing
      depression as compared with healthy subjects and patients with many other chronic
      neurological conditions. The observation that depressive symptoms can precede the
      onset of neurological symptoms suggests that depression may be related to early
      disease-specific processes. Several pathogenic mechanisms have been proposed to
      explain the etiology of depression in patients with MS. This article reviews the
      current evidence for the contribution of lesional, autoimmune, iatrogenic, and
      psychosocial factors. It appears that the etiology of depression is
      multifactorial and varies in individual patients with MS.

PMID- 21948888
TI  - Dopaminergic challenge with bromocriptine one month after mild traumatic brain
      injury: altered working memory and BOLD response.
AB  - Catecholamines, particularly dopamine, modulate working memory (WM). Altered
      sensitivity to dopamine might play a role in WM changes observed after traumatic
      brain injury (TBI). Thirty-one healthy controls (HC) and 26 individuals with mild
      TBI (MTBI) 1 month after injury were challenged with bromocriptine versus placebo
      before administration of a verbal WM functional MRI task. Bromocriptine was
      associated with improved WM performance in the HC but not the MTBI group. On
      bromocriptine, the MTBI group showed increased activation outside of a task
      specific region of interest. Findings are consistent with the hypothesis that
      individuals with MTBI have altered responsivity to dopamine.

PMID- 21948889
TI  - Cortical interactions during the experience of auditory verbal hallucinations.
AB  - Auditory verbal hallucinations (AVHs), the perception of voices in the absence of
      auditory stimuli, are common and distressing symptoms reported by 50%-80% of
      patients with schizophrenia. However, the results in a number of imaging and
      electrophysiological studies on the origins of AVH are not consistent, and the
      underlying pathophysiology remains unclear. The authors enrolled a group of
      schizophrenia patients and normal-control subjects, age 18-45 years. Two patient
      groups participated in the study; 1) a group of 8 patients with drug-resistant
      spontaneous AVHs; and 2) a group of 7 patients whose AVHs were successfully
      controlled with neuroleptic medication; along with 16 normal-control subjects.
      The entire sample had EEG recording done, with the AVH group told to press a
      button when they experienced a hallucination, and the other two groups randomly
      told when to press the button. In the AVH group, hallucinations were longer in
      the "eyes-closed" than "eyes-open" condition. There was spreading phase-coupling
      in the AVH group, intra- and inter-hemispherically, at left and right frontal and
      temporal areas, under both eyes-closed and eyes-open condition, during the
      experience of AVH. There was a statistically significant increase of alpha-band
      frequency-specific synchrony maximum values in the AVH group. AVHs are considered
      to be complex features, and, as such, they reflect abnormal functional
      connectivity in multiple related regions in both intra- and inter-hemispherical
      brain sites, primarily defined by phase-integration.

PMID- 21948890
TI  - Anxiety affects cognition differently in healthy apolipoprotein E epsilon4
      homozygotes and non-carriers.
AB  - It is not known whether apolipoprotein E epsilon4-an Alzheimer disease
      susceptibility gene-influences the effects of state-anxiety on executive
      functioning in healthy individuals. In a prospective cohort study of 185
      cognitively normal individuals, there were epsilon4 homozygotes, heterozygotes,
      and non-carriers, who did not differ in age, sex, years of education, cognitive
      test scores, psychotropic medications, and state- or trait-anxiety. However,
      higher anxiety was associated with significantly worse Trails B performance in
      the epsilon4 homozygotes, as compared with epsilon4 non-carriers. The association
      of executive-functioning difficulties and anxiety appears more likely to occur in
      persons who are most at risk for subsequent cognitive decline.

PMID- 21948891
TI  - The clinical presentation and imaging manifestation of psychosis and dementia in
      general paresis: a retrospective study of 116 cases.
AB  - In recent years, occurrence of "general paresis (GP)" has increased significantly
      because of the increasing incidence of syphilis in China. Early diagnosis plays a
      very important role for effective treatment. Incidence is becoming extensive
      enough to warrant an updated investigation of the clinical characteristics of GP.
      The authors retrospectively reviewed 116 cases of GP in Guangzhou, China, and
      analyzed its incidence and clinical appearance, as well as the characteristics of
      EEG, neuroradiology, serum, and cerebrospinal fluid examinations. Of the 116 GP
      patients, clinical symptoms presented frequently on admission were a variety of
      psychiatric-behavioral symptoms and varying degrees of dementia. Positive sucking
      reflex was the most common sign, as well as hyperreflexia and Argyll-Robertson
      pupil. EEG data mainly showed slightly abnormal EEG activity, with increased
      delta waves. Focal atrophy in one or multiple cerebral regions was evident on
      neuroimage. The prevalence of GP extends to various social strata or classes,
      with clinical presentation varying considerably among patients. For patients with
      progressive cognitive and behavioral deterioration, accompanied with psychotic
      and/or affective behavioral disorders or cerebral atrophy of unknown cause,
      general paresis should be considered.

PMID- 21948892
TI  - White-Matter damage in Clade C HIV-positive subjects: a diffusion tensor imaging
      study.
AB  - The relationship between cognitive impairment and white-matter integrity in human
      immunodeficiency virus (HIV) remains poorly understood, particularly in clade C.
      The authors utilized diffusion tensor imaging (DTI) and a comprehensive
      neuropsychological evaluation to investigate the relationship between cognitive
      impairment and white-matter integrity in HIV-positive subjects with clade C HIV.
      Forty-four HIV-infected individuals and 10 seronegative subjects were compared,
      using a whole-brain, voxel-based approach to define fractional anisotropy (FA)
      and mean diffusion (MD). Compared with healthy-control subjects, the HIV-infected
      group exhibited decreased FA in the corpus callosum, superior longitudinal
      fasciculus, and cingulum and sagittal stratum. This study provides evidence that
      white-matter integrity is compromised in individuals infected with clade C HIV.

PMID- 21948893
TI  - Family history of dementia predicts worse neuropsychological functioning among
      HIV-infected persons.
AB  - HIV-negative individuals with a family history of dementia (FHD) are more likely
      to develop dementia than those without FHD. Whether FHD increases risk for
      neuropsychological (NP) impairment in HIV+ persons is unknown. As part of a
      multisite study into HIV-associated neurocognitive disorders (HAND), the authors
      captured FHD with a free-response, self-report question, and assessed NP
      performance with a comprehensive battery of tests. The authors examined HIV+
      persons with (N=190) and without (N=916) self-reported FHD. Despite the fact that
      the FHD group had factors typically associated with better NP performance (e.g.,
      higher CD4 counts and estimated verbal IQ), persons with FHD had significantly
      worse NP ability than those without FHD as measured by a Global Deficit Score.
      Thus, FHD appears to be a risk factor for HAND; the mechanism(s) underlying how
      FHD contributes to NP impairment among HIV+ persons warrants study.

PMID- 21948894
TI  - Antiretroviral adherence and the nature of HIV-associated verbal memory
      impairment.
AB  - The authors investigated the relationship between antiretroviral adherence and
      HIV-associated verbal memory impairment. HIV-positive participants demonstrated
      poorer verbal memory than HIV-negative participants. Both good (>=90%) and poor
      (<90%) adherers displayed encoding deficits as compared with controls, but only
      poor adherers exhibited retrieval deficits. Encoding deficits primarily accounted
      for reduced delayed recall in good adherers, but both encoding and retrieval
      deficits accounted for reduced delayed recall in poor adherers. The retrieval
      difference between the adherence groups might be explained by a neuroprotective
      effect of good antiretroviral adherence or preexisting HIV-related retrieval
      deficits that result in poorer adherence.

PMID- 21948895
TI  - Factor analysis of repetitive behaviors in Autism as measured by the Y-BOCS.
AB  - The authors carried out a factor analysis of the Yale-Brown Obsessive-Compulsive
      Scale checklist at the category level in order to reduce the number of variables
      in this domain and ultimately identify possible endophenotypes; 181 children with
      autism were enrolled. The authors estimated a tetrachoric correlation matrix
      among the dichotomous symptom categories and then used exploratory and
      confirmatory factor analyses to identify a clinically meaningful factor structure
      for this correlation matrix. Their analysis supported a four-factor solution:
      obsessions, higher-order repetitive behaviors, lower-order repetitive behaviors,
      and hoarding. These findings are another step in the effort to identify
      genetically and biologically distinct groups within this population.

PMID- 21948896
TI  - Influence of premorbid psychopathology and lesion location on affective and
      behavioral disorders after ischemic stroke.
AB  - Early recognition of psychopathological symptoms (PSs) after stroke is important
      because they greatly influence the recovery of patients. The aim of this study
      was to investigate the predictive factors of PSs occurring in patients with
      ischemic stroke. Eighty-nine patients were prospectively evaluated upon admission
      and 4, 12, and 26 weeks later with the Neuropsychiatric Inventory, Hamilton's
      Rating Scales for Depression and Anxiety, and a battery of neuropsychological and
      functional scales. Depression and apathy were the most frequent PSs detected
      after stroke. Premorbid psychopathologies and right-hemisphere location were the
      main predictive indicators of early and long-term PSs.

PMID- 21948897
TI  - Theta-patterned, frequency-modulated priming stimulation enhances low-frequency,
      right prefrontal cortex repetitive transcranial magnetic stimulation (rTMS) in
      depression: a randomized, sham-controlled study.
AB  - Efficacy of repetitive, transcranial magnetic stimulation (rTMS) has been found
      in depression; however, doubt still remains about its effectiveness in clinical
      practice. In this context, results are being explored. The authors, describing
      new techniques to improve response rates to rTMS treatment, compared the efficacy
      of adjuvant, frequency-modulated, active-priming rTMS with sham-priming
      stimulation in the theta range in patients with moderate-to-severe depression
      receiving low-frequency rTMS. Forty patients with moderate-to-severe depression
      (ICD-10 DCR) were alternately assigned to receive add-on, active-priming rTMS (4
      8 Hz; 400 pulses, at 90% of motor threshold [MT]) or sham-priming stimulation
      followed by low-frequency rTMS (1-Hz; 900 pulses at 110% of MT) over the right
      dorsolateral prefrontal cortex. They were rated with the Structured Interview
      Guide for the Hamilton Depression Rating Scale (SIGH-D), the Brief Psychiatric
      Rating Scale (BPRS), and the Clinical Global Impression-Severity of Illness (CGI
      S) scale at baseline, after the 5th and 10th rTMS, and 2 weeks post-rTMS. For
      SIGH-D scores, there was significant improvement in the active group over time.
      Stepwise linear-regression analysis showed that age at onset significantly
      predicted SIGH-D scores after the 5th rTMS session in the active-priming group.
      Pre-stimulation with frequency-modulated priming stimulation in the theta range
      has greater antidepressant effect than low-frequency stimulation alone.

PMID- 21948898
TI  - Determining the impact of dementia on antidepressant treatment response in older
      adults.
AB  - Major depression is a common diagnosis in older individuals. The authors present
      preliminary findings on the response to sertraline in depressed elderly patients
      with and without dementia. Previous research on antidepressant treatment in
      elderly patients suggests that it is effective in treating depression. The
      authors followed depressed patients with and without dementia. Treatment response
      was more marked in the subgroup without dementia, but there was no statistically
      significant difference in response between the two subgroups. Depressed elderly
      patients with dementia may improve on antidepressant treatment, although
      treatment response may be less robust than in depressed patients without
      dementia.

PMID- 21948899
TI  - Atypical presentations of amyotrophic lateral sclerosis: a case report.
AB  - Amyotrophic lateral sclerosis (ALS) with atypical symptoms poses a diagnostic
      challenge to clinicians, frequently resulting in delayed diagnosis. The patient
      reported here presented with unexplained weight loss and was investigated for 8
      months, with an extensive work-up, including several imaging studies, especially
      to rule out neoplastic processes, before a diagnosis of ALS could be made,
      largely on the basis of upper and lower motor weakness.

PMID- 21948902
TI  - Does the "dynamic core" approach help to manage autistic behavioral disorders?

PMID- 21948903
TI  - Duloxetine's effects in resting functional magnetic resonance imaging of first
      episode, drug-naive major depressive disorder with panic disorder patients.

PMID- 21948904
TI  - Does memory impairment exclude a diagnosis of OCD after traumatic brain injury?

PMID- 21948905
TI  - Is it medication-induced psychosis or prodromal psychosis unmasked by medication?

PMID- 21948907
TI  - Hyperosmolar hyperglycemic nonketotic syndrome presenting with hemichorea
      hemiballismus: a case report.

PMID- 21948906
TI  - Amisulpride augmentation of clozapine in refractory schizophrenia.

PMID- 21948908
TI  - Improvement of oral dyskinesia after switching from aripiprazole to paliperidone:
      a case report.

PMID- 21948909
TI  - Probable psychosis associated with levetiracetam: a case report.

PMID- 21948910
TI  - Successful treatment of refractory organic catatonic disorder with repetitive
      transcranial magnetic stimulation (rTMS) therapy.

PMID- 21948911
TI  - Panic attack-like episodes possibly induced by pramipexole in a patient with
      young-onset Parkinson's disease.

PMID- 21948912
TI  - A parameter selection for differentiating between healthy and parkinsonian gait
      through modeling Parkinson's disease from a chaotic viewpoint.

PMID- 21948913
TI  - Hypomania as a genuine side effect of fluoxetine.

PMID- 21948914
TI  - Toward a unifying hypothesis for Schizophrenia and Autism visual fragmentation.

PMID- 21948915
TI  - Impulsivity is associated with decision-making deficits in de-novo Parkinson's
      disease.

PMID- 21948916
TI  - Mania and pachygyria.

PMID- 21948918
TI  - Psychiatric presentation in possible Susac's syndrome.

PMID- 21948917
TI  - Manic symptoms during a switch from risperidone to paliperidone: a case report.

PMID- 21948919
TI  - Rapid-onset cognitive impairment due to bilateral medial-thalamic infarcts.

PMID- 21948920
TI  - Psychosis secondary to ALS in the absence of dementia: a convincing case.

PMID- 21948921
TI  - A case of visual hypoemotionality induced by interferon alpha-2b therapy in a
      patient with chronic myeloid leukemia.

PMID- 21948922
TI  - Schizophrenia-like psychosis associated with right-parietal meningioma.

PMID- 21948923
TI  - Psychogenic movement disorder after H1N1 influenza vaccination.

PMID- 21948924
TI  - Geriatric manic delirium with no previous history of mania.

PMID- 21948925
TI  - Manic psychosis after sertraline and transcranial direct-current stimulation.

PMID- 21948926
TI  - Psychopharmacological treatment of obsessive-compulsive disorder comorbid with
      body dysmorphic disorder and pathological gambling disorder.

PMID- 21948927
TI  - Complex visual hallucinations, presumably due to subarachnoid hemorrhage, treated
      successfully with risperidone.

PMID- 21948928
TI  - The dorsal hippocampal commissure: when functionality matters.

PMID- 21948929
TI  - Elevated creatine kinase levels with second-generation antipsychotics.

PMID- 21948930
TI  - Aripiprazole-associated rhabdomyolysis in a patient with schizophrenia.

PMID- 21948931
TI  - Capgras syndrome related to left-hemisphere injury.

PMID- 21948932
TI  - Reduplicative paramnesia: dramatic improvement after neurosurgical treatment.

PMID- 21948933
TI  - An unusual case of anti-NMDA-receptor encephalitis in the Psychiatry Inpatient
      Unit.

PMID- 21948934
TI  - Expert attacks decision in US to stop use of bevacizumab for eye condition.

PMID- 21948935
TI  - An observational nationwide register based cohort study on lamotrigine versus
      lithium in bipolar disorder.
AB  - It is not clear whether the effectiveness of lamotrigine versus lithium differs
      for patients with bipolar disorder treated in clinical practice. We compared
      rates of switch to, or add on of, another psychotropic, and rates of psychiatric
      hospitalization for patients treated with lamotrigine or lithium in clinical
      practice. Using linkage of nationwide Danish registers we identified 730 patients
      who received lamotrigine and 3518 patients received lithium subsequent to a
      diagnosis of bipolar disorder in psychiatric hospital settings during a period
      from 1995 to 2006. The overall rate of switch to or add on of another
      psychotropic (the opposite drug of interest (lithium or lamotrigine),
      antidepressants, antipsychotics or other anticonvulsants than lamotrigine) was
      increased for lamotrigine compared with lithium (HR = 2.60, 95% CI: 2.23-3.04),
      regardless of whether the index episode was depressive, manic, mixed or
      remission. In addition, the overall rate of psychiatric hospitalization was
      increased for lamotrigine compared with lithium (HR = 1.45, 95% CI: 1.28-1.65),
      as were the rates for patients with a depressive (HR = 1.31, 95% CI: 1.01-1.70)
      and patients with a manic (HR = 1.65, 95% CI: 1.31-2.09) index episode. Rates did
      not differ significantly between the drugs for patients with a mixed index
      episode and for patients in remission. It is concluded that in daily clinical
      practice, treatment with lithium is in general superior to treatment with
      lamotrigine.

PMID- 21948936
TI  - Ginsenoside Rb3 exerts antidepressant-like effects in several animal models.
AB  - Total ginsenosides have been shown to have therapeutic actions as
      antidepressants. We report a major active ingredient of total ginsenosides, the
      ginsenoside Rb3 (Rb3), which may have antidepressant-like effects. Using the
      forced swim test, tail suspension test, and learned helplessness procedure, we
      found that Rb3 had significant anti-immobility effects in mice in the forced swim
      and tail suspension tests and reduced the number of escape failures in the
      learned helplessness procedure. In a reserpine-induced syndrome model, Rb3
      attenuated hypothermia, palpebral ptosis, and akinesia. In the chronic mild
      stress model, chronic Rb3 administration reversed the decrease in locomotor
      activity, novelty-suppressed feeding, and sucrose preference. Furthermore,
      neurochemical tests were performed to support our hypothesis that biochemical
      variations (i.e. brain-derived neurotrophic factor and the monoamine
      neurotransmitters 5-hydroxytryptamine, dopamine, and norepinephrine) are involved
      in Rb3's antidepressant-like effects. Finally, we found, using whole-cell patch
      clamp recordings, that the action potential transmission in neurons within the
      somatosensory cortex was excited by Rb3 perfusion and blocked with Panax
      notoginseng total saponins extracted from leaves. This study provides evidence
      for the mechanism of action of the antidepressant-like effects of Rb3.

PMID- 21948937
TI  - Nicotine-induced anxiogenic-like behaviours of rats in the elevated plus-maze:
      possible role of NMDA receptors of the central amygdala.
AB  - The objective of the present study was to investigate the possible role of the N
      methyl-D-aspartate (NMDA) receptor system of the central amygdala (CeA) in the
      anxiogenic-like effect of nicotine. Male Wistar rats with cannulas aimed to the
      CeA were submitted to the elevated plus-maze (EPM). Intraperitoneal (i.p.)
      injections of nicotine (0.6 and 0.8 mg/kg) decreased percentage open arm time
      spent (%OAT) and percentage open arm entries (%OAE), but not locomotor activity,
      indicating an anxiogenic-like response. Bilateral intra-CeA microinjection of
      NMDA (0.005-0.1 MU g/rat) decreased %OAT, but not %OAE and locomotor activity.
      Moreover, intra-CeA microinjection of NMDA (0.05 MU g) with an ineffective dose
      of nicotine (0.4 mg/kg, i.p.) reduced %OAT and %OAE without effect on locomotor
      activity. On the other hand, intra-CeA microinjection of the NMDA receptor
      antagonist D-AP5 (0.05-0.5 MU g/rat) increased both %OAT and %OAE, showing an
      anxiolytic-like effect of the drug. Co-administration of the same doses of D-AP5
      with nicotine (0.6 mg/kg, i.p.) increased %OAT and %OAE, but not locomotor
      activity. Intra-CeA microinjection of D-AP5 reversed the response induced by NMDA
      (0.1 MU g/rat) in the EPM. The results may support the possible involvement of
      glutamate transmission, through NMDA receptors of central amygdala in the
      anxiogenic-like effect of nicotine in the EPM task.

PMID- 21948938
TI  - Systematic review of national and international guidelines on attention-deficit
      hyperactivity disorder.
AB  - During the last few years several clinical guidelines on attention-deficit
      hyperactivity disorder (ADHD) have been published by national and international
      medical societies. To systematically review and compare recommendations of
      selected ADHD guidelines, we performed a systematic search in online guideline
      databases and PubMed in order to retrieve guideline texts. Guidelines meeting
      inclusion criteria were reviewed and recommendations on assessment and treatment
      extracted. The AGREE instrument was used to assess methodological quality. Of the
      26 guidelines identified, 13 were selected for further analysis: 11 guidelines
      deal with ADHD in childhood and adolescence and 5 guidelines cover transitional
      patients and/or ADHD in adults. The methodological quality of ADHD guidelines is
      moderate to good. They reflect similarities and differences of healthcare
      systems. Diagnosis throughout the lifespan is based on a detailed clinical
      history. There is greater agreement on evidence-based pharmacological treatment
      than on psychosocial interventions, reflecting the strength of evidence.

PMID- 21948940
TI  - Acute visual neglect and extinction: distinct functional state of the
      visuospatial attention system.
AB  - The neural mechanisms underlying spatial neglect are still disputed. Abnormal
      left parietal hyperactivation is proposed to lead to the rightward attentional
      bias, a clinical hallmark of neglect. Extinction, another deficit of visuospatial
      attention, is regarded as either a 'mild' form of neglect or a distinct syndrome.
      Although both neglect and extinction are typical syndromes of acute right
      hemispheric stroke, all imaging studies investigating these syndromes were
      conducted at least several weeks after stroke onset, in a phase when brain
      reorganization has already progressed. The present study aimed at comparing the
      activation patterns in acute stroke patients with neglect and extinction during
      visuospatial processing. Using functional magnetic resonance imaging, we examined
      the functional state of the attention system in 33 patients with a first ever
      stroke (53 +/- 5 h after stroke onset) and age-matched healthy subjects (n = 15).
      All patients had embolic infarcts within the territory of the right middle
      cerebral artery. Patients were divided into three groups: (i) normal visuospatial
      processing (control patients, n = 11); (ii) patients with visual extinction but
      with no signs of neglect (n = 9); and (iii) patients with visual neglect (n =
      13). While undergoing functional magnetic resonance imaging, patients performed a
      Posner-like task for visuospatial attention with detection of the targets in the
      left and right visual hemifields. Patients with neglect showed the expected
      imbalance in the left versus right parietal activation, which however, was
      present also in control and extinction patients, thus representing an
      epiphenomenon of the acute structural lesion in the right hemisphere. Compared
      with control patients, neglect was characterized by reduced activation in the
      right parietal and lateral occipital cortex, as well as in the left frontal eye
      field. In contrast, the activation pattern in patients with extinction differed
      from all other groups by an increased activation of the left prefrontal cortex.
      In both patients with neglect and extinction, detection of targets in the left
      hemifield correlated with an activation in the left prefrontal and parietal
      cortex. Thus at least in acute stroke, a relative hyperactivation of the left
      parietal cortex is not a particular characteristic of neglect. The specific
      signature of neglect is represented by the dysfunction of the right parietal and
      lateral occipital cortex. The function of the left attentional centres might
      provide a compensatory role after critical right hemisphere lesions and be
      relevant for the contralesional spatial processing.

PMID- 21948939
TI  - Rhythm in disguise: why singing may not hold the key to recovery from aphasia.
AB  - The question of whether singing may be helpful for stroke patients with non
      fluent aphasia has been debated for many years. However, the role of rhythm in
      speech recovery appears to have been neglected. In the current lesion study, we
      aimed to assess the relative importance of melody and rhythm for speech
      production in 17 non-fluent aphasics. Furthermore, we systematically alternated
      the lyrics to test for the influence of long-term memory and preserved motor
      automaticity in formulaic expressions. We controlled for vocal frequency
      variability, pitch accuracy, rhythmicity, syllable duration, phonetic complexity
      and other relevant factors, such as learning effects or the acoustic setting.
      Contrary to some opinion, our data suggest that singing may not be decisive for
      speech production in non-fluent aphasics. Instead, our results indicate that
      rhythm may be crucial, particularly for patients with lesions including the basal
      ganglia. Among the patients we studied, basal ganglia lesions accounted for more
      than 50% of the variance related to rhythmicity. Our findings therefore suggest
      that benefits typically attributed to melodic intoning in the past could actually
      have their roots in rhythm. Moreover, our data indicate that lyric production in
      non-fluent aphasics may be strongly mediated by long-term memory and motor
      automaticity, irrespective of whether lyrics are sung or spoken.

PMID- 21948941
TI  - Cataract surgery outcome at a rural eye care hospital in India.
AB  - We report the final outcomes, based on final visual acuity, of patients who
      underwent cataract surgery at an outreach rural ophthalmology unit and document
      the details of the ophthalmic examination, type of surgery, intra- and
      postoperative complications and the final visual acuity. Of 208 eyes (198
      patients), 81.3% had small incision cataract surgery and 18.7% had
      phacoemulsification. We believe that, with good planning and the proper
      utilization of available resources, it is possible to achieve a good visual
      outcome in the great majority of cases.

PMID- 21948942
TI  - Switch to adalimumab in patients with Crohn's disease controlled by maintenance
      infliximab: prospective randomised SWITCH trial.
AB  - BACKGROUND: Elective switching between anti-tumour necrosis factor (TNF) agents
      not necessarily dictated by efficacy or tolerability occurs in clinical practice.
      A study was undertaken to evaluate prospectively the impact of elective switching
      of patients with Crohn's disease well controlled with intravenous infliximab to
      subcutaneous adalimumab in a controlled trial. METHODS: An open-label randomised
      single-centre trial recruited 73 patients with ongoing response to at least 6
      months of scheduled maintenance infliximab. Patients were randomised to continue
      intravenous 5 mg/kg infliximab or to switch to subcutaneous adalimumab 80 mg at
      baseline followed by 40 mg every other week for 1 year. Dose optimisation was
      allowed for intermittent flares, and patients with loss of response or
      intolerance could cross over to the alternative treatment group. Tolerability,
      patient preference and efficacy of both treatment options were the primary
      outcomes. RESULTS: Dose optimisation or interruption of treatment occurred in
      17/36 patients (47%) in the adalimumab group and in 6/37 patients (16%) in the
      infliximab group (p=0.006). One patient interrupted infliximab treatment and 10
      patients interrupted adalimumab treatment (p=0.003), mostly for loss of
      tolerance. Overall, patients preferred adalimumab treatment. All five serious
      adverse events were related to complicated Crohn's disease and occurred in
      patients randomised to adalimumab. Injection site reactions were more frequent
      than infusion reactions (8 vs 1, p=0.01), but only the latter caused cessation of
      further dosing. Anti-TNF serum levels were stable throughout the 1-year period in
      both groups. CONCLUSION: Elective switching from infliximab to adalimumab is
      associated with loss of tolerance and loss of efficacy within 1 year. Adherence
      to the first anti-TNF agent is recommended.

PMID- 21948943
TI  - Gene expression dynamics after murine pancreatitis unveils novel roles for
      Hnf1alpha in acinar cell homeostasis.
AB  - OBJECTIVES: During pancreatitis, specific transcriptional programmes govern
      functional regeneration after injury. The objective of this study was to analyse
      the dynamic regulation of pancreatic genes and the role of transcriptional
      regulators during recovery from pancreatitis. DESIGN: Wild-type and genetically
      modified mice (Hnf1alpha(-/-) and Ptf1a(+/-)) were used. After caerulein or L
      arginine induced pancreatitis, blood or pancreata were processed for enzymatic
      assays, ELISA, histology, immunohistochemistry, western blotting and quantitative
      reverse transcriptase-PCR. Nr5a2 promoter reporter and chromatin
      immunoprecipitation assays for Hnf1alpha were also performed. RESULTS: After
      caerulein pancreatic injury, expression of acinar and endocrine genes rapidly
      decreased, but eventually recovered, depicting distinct cell-type-specific
      patterns. Pdx1 and Hnf1alpha mRNAs underwent marked downregulation, matching
      endocrine/exocrine gene expression profiles. Ptf1a, Pdx1 and Hnf1alpha protein
      levels were also reduced and recovered gradually. These changes were associated
      with transient impairment of exocrine and endocrine function, including abnormal
      glucose tolerance. On l-arginine pancreatitis, changes in Ptf1a, Pdx1 and
      Hnf1alpha gene and protein expression were recapitulated. Reduced Hnf1alpha and
      Ptf1a levels after pancreatitis coincided with increased acinar cell
      proliferation, both in Hnf1alpha(-/-) and Ptf1a(+/-) mice. Moreover, Hnf1alpha(-/
      ) mice had reduced Ptf1a protein as well as transcripts for Ptf1a and digestive
      enzymes. Dispersed acini from Hnf1alpha(-/-) mice showed suboptimal secretory
      responses to caerulein. Bioinformatics analysis did not support a role for
      Hnf1alpha as a direct regulator of digestive enzyme genes. Instead, it was found
      that Hnf1alpha binds to, and regulates, the promoter of Nr5a2, coding an orphan
      nuclear receptor that regulates acinar gene expression. CONCLUSIONS: Dynamic
      changes in gene expression occur on pancreatitis induction, determining altered
      exocrine and endocrine function. This analysis uncovers roles for Hnf1alpha in
      the regulation of acinar cell determination and function. This effect may be
      mediated, in part, through direct regulation of Nr5a2.

PMID- 21948944
TI  - Interleukin 21 controls tumour growth and tumour immunosurveillance in colitis
      associated tumorigenesis in mice.
AB  - BACKGROUND AND AIMS: Colitis-associated tumorigenesis is a balance between
      proliferation of tumour cells and tumour immunosurveillance. The role of T-helper
      cell-derived cytokines in tumour growth is not fully understood. In this study
      the authors investigated the influence of interleukin (IL) 21 on intestinal
      tumorigenesis. METHODS: Chronic colitis was induced in IL-21(-/-) and littermate
      control wild-type mice with three cycles of 1.5% dextran sulphate sodium (DSS)
      over 7 days followed by 7 days of drinking water. Mice received an azoxymethane
      injection on day 0 of DSS-colitis to induce tumorigenesis. Immunohistochemistry
      was performed on inflamed and tumour-bearing areas of colons. Cytokine expression
      of isolated colonic CD4 T cells was determined by ELISA. Cytotoxic capacity of
      isolated colonic CD8 T cells targeting tumour cells was evaluated by flow
      cytometry and quantitative cytotoxicity assay. Apoptosis of tumour cells was
      determined by TUNEL assay of colonic sections. RESULTS: Increasing expression of
      IL-21 was observed in chronic colitis, which showed functional importance, since
      IL-21 deficiency prevented chronic DSS-colitis development. Further, in the
      absence of IL-21, significantly fewer tumour nodules were detected, despite a
      similar extent of intestinal inflammation. In wild-type mice, 8.6+/-1.9 tumour
      nodules were found compared with 1.0+/-1.2 in IL-21-deficient mice. In tumour
      bearing IL-21-deficient mice, intestinal inflammation was restored and partly
      dependent on interferon (IFN)-gamma, whereas the inflammation in wild-type mice
      showed high IL-17A concentrations. In these rare tumours in IL-21-deficient mice,
      tumour cell proliferation (Ki-67) was decreased, while cell apoptosis was
      increased, compared with wild-type mice. Increased IFNgamma expression in tumour
      bearing IL-21-deficient mice led to increased tumour immunosurveillance mediated
      by cytotoxic CD8CD103 T cells targeting E-cadherin(+) colonic tumour cells and
      therefore limited tumour growth. CONCLUSION: These results indicate that IL-21
      orchestrates colitis-associated tumorigenesis, leading to the hypothesis that
      high IFNgamma and low IL-17A expression reduces tumour cell proliferation and
      increases tumour immunosurveillance.

PMID- 21948946
TI  - Dietary haem stimulates epithelial cell turnover by downregulating feedback
      inhibitors of proliferation in murine colon.
AB  - OBJECTIVE: Colon cancer is a leading cause of cancer deaths in Western countries
      and is associated with diets high in red meat. Haem, the iron-porphyrin pigment
      of red meat, induces cytotoxicity of gut contents and damages the colon surface
      epithelium. Compensatory hyperproliferation leads to epithelial hyperplasia which
      increases the risk of colon cancer. The aim of this study was to identify
      molecules signalling from the surface epithelium to the crypt to initiate
      hyperproliferation upon stress induced by haem. METHODS: C57Bl6/J mice
      (n=9/group) received a 'westernised' control diet (40 en% fat) with or without
      0.5 MUmol/g haem for 14 days. Colon mucosa was used to quantify cell
      proliferation and for microarray transcriptome analysis. Gene expression profiles
      of surface and crypt cells were compared using laser capture microdissection.
      Protein levels of potential signalling molecules were quantified. RESULTS: Haem
      fed mice showed epithelial hyperproliferation and decreased apoptosis, resulting
      in hyperplasia. Microarray analysis of the colon mucosa showed 3710
      differentially expressed genes (false discovery rate (q) <0.01), with many
      involved in the cell cycle. Expression levels of haem- and stress-related genes
      showed that haem affected surface cells but did not directly affect crypt cells.
      Injured surface cells should therefore signal to crypt cells to induce
      compensatory hyperproliferation. Haem downregulated the inhibitors of
      proliferation, Wnt inhibitory factor 1, Indian Hedgehog and bone morphogenetic
      protein 2. Interleukin-15 was also downregulated. Haem upregulated amphiregulin,
      epiregulin and cyclo-oxygenase-2 mRNA in surface cells. Their protein/metabolite
      levels were, however, not increased as haem induced surface-specific inhibition
      of translation by increasing 4E-BP1. CONCLUSIONS: Haem induces colonic
      hyperproliferation and hyperplasia by inhibiting the surface to crypt signalling
      of feedback inhibitors of proliferation.

PMID- 21948947
TI  - Elevated intracellular Ca2+ reveals a functional membrane nucleotide pool in
      intact human red blood cells.
AB  - Elevated intracellular calcium generates rapid, profound, and irreversible
      changes in the nucleotide metabolism of human red blood cells (RBCs), triggered
      by the adenosine triphosphatase (ATPase) activity of the powerful plasma membrane
      calcium pump (PMCA). In the absence of glycolytic substrates, Ca(2+)-induced
      nucleotide changes are thought to be determined by the interaction between PMCA
      ATPase, adenylate kinase, and AMP-deaminase enzymes, but the extent to which this
      three-enzyme system can account for the Ca(2+)-induced effects has not been
      investigated in detail before. Such a study requires the formulation of a model
      incorporating the known kinetics of the three-enzyme system and a direct
      comparison between its predictions and precise measurements of the Ca(2+)-induced
      nucleotide changes, a precision not available from earlier studies. Using state
      of-the-art high-performance liquid chromatography, we measured the changes in the
      RBC contents of ATP, ADP, AMP, and IMP during the first 35 min after ionophore
      induced pump-saturating Ca(2+) loads in the absence of glycolytic substrates.
      Comparison between measured and model-predicted changes revealed that for good
      fits it was necessary to assume mean ATPase V(max) values much higher than those
      ever measured by PMCA-mediated Ca(2+) extrusion. These results suggest that the
      local nucleotide concentrations generated by ATPase activity at the inner
      membrane surface differed substantially from those measured in bulk cell
      extracts, supporting previous evidence for the existence of a submembrane
      microdomain with a distinct nucleotide metabolism.

PMID- 21948948
TI  - The Na conductance in the sarcolemma and the transverse tubular system membranes
      of mammalian skeletal muscle fibers.
AB  - Na (and Li) currents and fluorescence transients were recorded simultaneously
      under voltage-clamp conditions from mouse flexor digitorum brevis fibers stained
      with the potentiometric dye di-8-ANEPPS to investigate the distribution of Na
      channels between the surface and transverse tubular system (TTS) membranes. In
      fibers rendered electrically passive, voltage pulses resulted in step-like
      fluorescence changes that were used to calibrate the dye response. The effects of
      Na channel activation on the TTS voltage were investigated using Li, instead of
      Na, because di-8-ANEPPS transients show anomalies in the presence of the latter.
      Na and Li inward currents (I(Na), I(Li); using half of the physiological ion
      concentration) showed very steep voltage dependences, with no reversal for
      depolarizations beyond the calculated equilibrium potential, suggesting that most
      of the current originates from a noncontrolled membrane compartment. Maximum peak
      I(Li) was ~ 30% smaller than for I(Na), suggesting a Li-blocking effect. I(Li)
      activation resulted in the appearance of overshoots in otherwise step-like di-8
      ANEPPS transients. Overshoots had comparable durations and voltage dependence as
      those of I(Li). Simultaneously measured maximal overshoot and peak I(Li) were 54
      +/- 5% and 773 +/- 53 uA/cm(2), respectively. Radial cable model simulations
      predicted the properties of I(Li) and di-8-ANEPPS transients when TTS access
      resistances of 10-20 Omega cm(2), and TTS-to-surface Na permeability density
      ratios in the range of 40:60 to 70:30, were used. Formamide-based osmotic shock
      resulted in incomplete detubulation. However, results from a subpopulation of
      treated fibers (low capacitance) provide confirmatory evidence that a significant
      proportion of I(Li), and the overshoot in the optical signals, arises from the
      TTS in normal fibers. The quantitative evaluation of the distribution of Na
      channels between the sarcolemma and the TTS membranes, as provided here, is
      crucial for the understanding of the radial and longitudinal propagation of the
      action potential, which ultimately govern the mechanical activation of muscle in
      normal and diseased conditions.

PMID- 21948949
TI  - 5-HT3 receptor ion size selectivity is a property of the transmembrane channel,
      not the cytoplasmic vestibule portals.
AB  - 5-HT3A receptors select among permeant ions based on size and charge. The
      membrane-associated (MA) helix lines the portals into the channel's cytoplasmic
      vestibule in the 4-A resolution structure of the homologous acetylcholine
      receptor. 5-HT3A MA helix residues are important determinants of single-channel
      conductance. It is unknown whether the portals into the cytoplasmic vestibule
      also determine the size selectivity of permeant ions. We sought to determine
      whether the portals form the size selectivity filter. Recently, we showed that
      channels functioned when the entire 5-HT3A M3-M4 loop was replaced by the
      heptapeptide M3-M4 loop sequence from GLIC, a bacterial Cys-loop neurotransmitter
      gated ion channel homologue from Gloebacter violaceus. We used homomeric 5-HT3A
      receptors with either a wild-type (WT) M3-M4 loop or the chimeric heptapeptide (5
      HT3A-glvM3M4) loop, i.e., with or without portals. In Na(+)-containing buffer,
      the WT receptor current-voltage relationship was inwardly rectifying. In
      contrast, the 5-HT3A-glvM3M4 construct had a negative slope conductance region at
      voltages less than -80 mV. Glutamine substitution for the heptapeptide M3-M4 loop
      arginine eliminated the negative slope conductance region. We measured the
      relative permeabilities and conductances of a series of inorganic and organic
      cations ranging from 0.9 to 4.5 A in radius (Li(+), Na(+), ammonium,
      methylammonium, ethanolammonium, 2-methylethanolammonium, dimethylammonium,
      diethanolammonium, tetramethylammonium, choline, tris [hydroxymethyl]
      aminomethane, and N-methyl-d-glucamine). Both constructs had measurable
      conductances with Li(+), ammonium, and methylammonium (size range of 0.9-1.8-A
      radius). Many of the organic cations >2.4 A acted as competitive antagonists
      complicating measurement of conductance ratios. Analysis of the permeability
      ratios by excluded volume theory indicates that the minimal pore radius for 5
      HT3A and 5-HT3-glvM3M4 receptors was similar, ~ 5 A. We infer that the 5-HT3A
      size selectivity filter is located in the transmembrane channel and not in the
      portals into the cytoplasmic vestibule. Thus, the determinants of size
      selectivity and conductance are located in physically distinct regions of the
      channel protein.

PMID- 21948950
TI  - Perioperative management of clopidogrel therapy: the effects on in-hospital
      cardiac morbidity in older patients with hip fractures.
AB  - BACKGROUND: Increasing numbers of older patients prescribed clopidogrel are
      presenting for urgent hip fracture surgery. Best practice for the management of
      clopidogrel therapy is unknown, although delays to surgery are associated with
      increased mortality. We investigated the influence of perioperative management of
      clopidogrel therapy on in-hospital cardiac morbidity and transfusion in this
      population. METHODS: Retrospective review of all patients aged >60 yr, admitted
      to a single centre with hip fractures between June 2005 and November 2008. Acute
      coronary syndrome (ACS) was defined as a raised plasma troponin concentration
      >0.04 ug litre(-1) associated with chest pain, new ECG changes, or both. RESULTS:
      Of 1381 patients admitted with hip fractures, 114 were receiving regular
      clopidogrel therapy with a median age of 83.7 (60-98) yr. Clopidogrel was
      withheld perioperatively in 111 (98%) of these patients. Twenty-three patients
      (20.2%) suffered an ACS. Risk peaked for ACS [odds ratio (OR) 6.7 (95% confidence
      interval, CI, 1.7-25.8)] (P=0.006) between days 4 and 8 after clopidogrel
      withdrawal. The OR for requiring a blood transfusion during or after surgery
      peaked at day 1 after clopidogrel withdrawal [OR 2.31 (95% CI, 1.02-5.21)]
      (P=0.044). CONCLUSIONS: The length of withdrawal of clopidogrel therapy
      perioperatively was associated with a significantly increased incidence of ACS.
      An association between shorter withdrawal and increased blood transfusion
      requirements was also seen. The study emphasizes the cardiovascular risks of
      routinely interrupting clopidogrel therapy in this at-risk population and that a
      more considered, individualized, evidenced-based approach is needed.

PMID- 21948951
TI  - Thoracic epidural analgesia or patient-controlled local analgesia for radical
      retropubic prostatectomy: a randomized, double-blind study.
AB  - BACKGROUND: Postoperative pain after radical retropubic prostatectomy is moderate
      to severe. The primary aim of this study was to assess whether intra-abdominal
      local anaesthetics provide similar analgesia compared with thoracic epidural
      analgesia (TEA). METHODS: Fifty patients, ASA I-II, participated in this
      prospective, double-blinded study. All patients had TEA. After operation, they
      were randomized into two groups of 25 patients: Group PCLA (patient-controlled
      local analgesia): self-administration of 10 ml of ropivacaine 2 mg ml-1 via the
      intra-abdominal catheter for 48 h. Group TEA: infusion of 10 ml h-1 of
      ropivacaine 1 mg ml-1, fentanyl 2 MUg ml-1, and epinephrine 2 MUg ml-1 epidurally
      for 48 h. The primary endpoint was pain on coughing at 4 h after operation.
      Rescue medication was morphine i.v. as required. RESULTS: Pain on coughing at 4,
      24, and 48 h was significantly lower in Group TEA [0 (0-10)] compared with Group
      PCLA [4 (0-10)] (P<0.05). Significantly lower pain intensity was also found in
      Group TEA compared with Group PCLA at the incision site, deep pain, and pain on
      coughing at 4 and 24 h (P<0.05). Morphine consumption was significantly greater
      in Group PCLA [12 (0-46)] compared with Group TEA [0 (0-20)] at 0-48 h after
      operation [median (range)] (P=0.015). Maximum expiratory pressure was higher in
      Group TEA compared with Group PCLA at 24 h (P<0.01). CONCLUSIONS: TEA provides
      superior postoperative pain relief with better preservation of expiratory muscle
      strength compared with PCLA.

PMID- 21948952
TI  - Development and implementation of a nutrition intervention programme in North
      West Pakistan: a realist framework.
AB  - Maternal and infant malnutrition is prevalent in rural regions of NW Pakistan.
      This article reports on the use of a combination of a realist Context-Mechanism
      Outcome framework and participatory appraisal methods to facilitate the
      development of a locally sensitive and responsive nutritional intervention
      programme. Data were gathered through a series of focus group (FG) discussions
      with local lady health workers, as well as pregnant and breastfeeding women
      attending an Emergency Field Hospital in North West Pakistan between May 2008 and
      March 2009. A nutrition intervention programme was implemented that involved
      cookery demonstration kitchens and free food supplements, coupled with nutrition
      and healthcare information and advice for pregnant and breastfeeding women.
      Subsequent FG discussions revealed that the programme had a positive impact on
      knowledge gained by women in the community and generated an openness to receiving
      and spreading knowledge. The framework, which rested on the use of a double
      feedback loop, involving local women, lady health workers, local researchers and
      UK-based researchers, has enabled not only the establishment of the programme,
      but has also given the local team the tools to apply for, and gain, further
      funding for the development of nutrition support services. The development of
      such methodological tools, which empower local researchers and service providers
      (wherever located) to operationalize local knowledge and assess interventions, is
      particularly relevant in international financially-constrained contexts.

PMID- 21948953
TI  - Short reads, circular genome: skimming solid sequence to construct the bighorn
      sheep mitochondrial genome.
AB  - As sequencing technology improves, an increasing number of projects aim to
      generate full genome sequence, even for nonmodel taxa. These projects may be
      feasibly conducted at lower read depths if the alignment can be aided by
      previously developed genomic resources from a closely related species. We
      investigated the feasibility of constructing a complete mitochondrial (mt) genome
      without preamplification or other targeting of the sequence. Here we present a
      full mt genome sequence (16,463 nucleotides) for the bighorn sheep (Ovis
      canadensis) generated though alignment of SOLiD short-read sequences to a
      reference genome. Average read depth was 1240, and each base was covered by at
      least 36 reads. We then conducted a phylogenomic analysis with 27 other bovid
      mitogenomes, which placed bighorn sheep firmly in the Ovis clade. These results
      show that it is possible to generate a complete mitogenome by skimming a low
      coverage genomic sequencing library. This technique will become increasingly
      applicable as the number of taxa with some level of genome sequence rises.

PMID- 21948955
TI  - Attitudes trigger motor behavior through conditioned associations: neural and
      behavioral evidence.
AB  - It has long been argued that attitudes prepare the body to act. While early
      evidence suggested that evaluations (positive or negative) are rigidly linked to
      specific motor behaviors (approach or avoidant), recent behavioral evidence
      suggests that this linkage is context dependent. Here, we report that the neural
      circuitry mediating the relationship between evaluations and motor responses
      promotes flexibility in our embodiment of attitudes. In a behavioral study,
      stimulus-response relationships between evaluations and actions were rapidly
      conditioned. In a neuroimaging (functional magnetic resonance imaging) study,
      repetition suppression demonstrated that these relationships are formed in neural
      systems traditionally implicated in arbitrary sensorimotor mappings (i.e. the
      dorsal premotor cortex and posterior superior parietal lobule). These data
      provide the first neurophysiological evidence for attitude embodiment and
      demonstrate that relationships between evaluation and action are inherently
      malleable.

PMID- 21948954
TI  - Personality modulates the effects of emotional arousal and valence on brain
      activation.
AB  - The influence of personality on the neural correlates of emotional processing is
      still not well characterized. We investigated the relationship between
      extraversion and neuroticism and emotional perception using functional magnetic
      resonance imaging (fMRI) in a group of 23 young, healthy women. Using a
      parametric modulation approach, we examined how the blood oxygenation level
      dependent (BOLD) signal varied with the participants' ratings of arousal and
      valence, and whether levels of extraversion and neuroticism were related to these
      modulations. In particular, we wished to test Eysenck's biological theory of
      personality, which links high extraversion to lower levels of reticulothalamic
      cortical arousal, and neuroticism to increased reactivity of the limbic system
      and stronger reactions to emotional arousal. Individuals high in neuroticism
      demonstrated reduced sustained activation in the orbitofrontal cortex (OFC) and
      attenuated valence processing in the right temporal lobe while viewing emotional
      images, but an increased BOLD response to emotional arousal in the right medial
      prefrontal cortex (mPFC). These results support Eysenck's theory, as well as our
      hypothesis that high levels of neuroticism are associated with attenuated reward
      processing. Extraversion was inversely related to arousal processing in the right
      cerebellum, but positively associated with arousal processing in the right
      insula, indicating that the relationship between extraversion and arousal is not
      as simple as that proposed by Eysenck.

PMID- 21948956
TI  - Poor prognostic value of the modified Mallampati score: a meta-analysis involving
      177 088 patients.
AB  - The modified Mallampati score is used to predict difficult tracheal intubation.
      We have conducted a meta-analysis of published studies to evaluate the Mallampati
      score as a prognostic test. A total of 55 studies involving 177 088 patients were
      included after comprehensive electronic and manual searches. The pooled estimates
      from the meta-analyses were calculated based on a random-effects model and a
      summary receiver operating curve. Meta-regression analyses were performed to
      explore sources of possible heterogeneity between the studies. The summary
      receiver operating curve demonstrated an area under the curve of 0.75. The pooled
      odds ratio for a difficult intubation with a modified Mallampati score of III or
      IV was 5.89 [95% confidence interval (CI), 4.74-7.32]. The pooled estimates of
      the specificity and sensitivity were 0.91 (CI, 0.91-0.91) and 0.35 (CI, 0.34
      0.36), respectively. The pooled positive and negative likelihood ratios were 4.13
      (CI, 3.60-4.66) and 0.70 (CI, 0.65-0.75), respectively. The meta-analyses had
      statistical and clinical heterogeneity ranging from 87.2% to 99.4%. Meta
      regression analyses did not identify any significant explanation of the
      heterogeneity. We conclude that the prognostic value of the modified Mallampati
      score was worse than that estimated by previous meta-analyses. Our assessment
      shows that the modified Mallampati score is inadequate as a stand-alone test of a
      difficult laryngoscopy or tracheal intubation, but it may well be a part of a
      multivariate model for the prediction of a difficult tracheal intubation.

PMID- 21948957
TI  - Is Accelerated Partner Therapy (APT) a cost-effective alternative to routine
      patient referral partner notification in the UK? Preliminary cost-consequence
      analysis of an exploratory trial.
AB  - OBJECTIVES: To undertake a cost-consequence analysis to assess two new models of
      partner notification (PN), known as Accelerated Partner Therapy (APT Hotline and
      APT Pharmacy), as compared with routine patient referral PN, for sex partners of
      people with chlamydia, gonorrhoea and non-gonococcal urethritis. METHODS:
      Comparison of costs and outcomes alongside an exploratory trial involving two
      genitourinary medicine clinics and six community pharmacies. Index patients
      selected the PN method (APT Hotline, APT Pharmacy or routine PN) for their
      partners. Clinics and pharmacies recorded cost and resource use data including
      duration of consultation and uptake of treatment pack. Cost data were collected
      prospectively for two out of three interventions, and data were synthesised and
      compared in terms of effectiveness and costs. RESULTS: Routine PN had the lowest
      average cost per partner treated (approximately L46) compared with either APT
      Hotline (approximately L54) or APT Pharmacy (approximately L53) strategies. The
      cost-consequence analysis revealed that APT strategies were more costly but also
      more effective at treating partners compared to routine PN. CONCLUSION: The
      hotline strategy costs more than both the alternative PN strategies. If we accept
      that strategies which identify and treat partners the fastest are likely to be
      the most effective in reducing reinfection and onward transmission, then APT
      Hotline appears an effective PN strategy by treating the highest number of
      partners in the shortest duration. Whether the additional benefit is worth the
      additional cost cannot be determined in this preliminary analysis. These data
      will be useful for informing development of future randomised controlled trials
      of APT.

PMID- 21948958
TI  - Combined blockade of integrin-alpha4beta1 plus cytokines SDF-1alpha or IL-1beta
      potently inhibits tumor inflammation and growth.
AB  - Tumor-associated macrophages promote tumor growth by stimulating angiogenesis and
      suppressing antitumor immunity. Thus, therapeutics that inhibit macrophage
      recruitment to tumors may provide new avenues for cancer therapy. In this study,
      we showed how chemoattractants stromal cell-derived growth factor 1 alpha (SDF
      1alpha) and interleukin 1 beta (IL-1beta) collaborate with myeloid cell integrin
      alpha4beta1 to promote tumor inflammation and growth. We found that SDF-1alpha
      and IL-1beta are highly expressed in the microenvironments of murine lung,
      pancreatic, and breast tumors; surprisingly, SDF-1alpha was expressed only by
      tumor cells, whereas IL-1beta was produced only by tumor-derived granulocytes and
      macrophages. In vivo, both factors directly recruited proangiogenic macrophages
      to tissues, whereas antagonists of both factors suppressed tumor inflammation,
      angiogenesis, and growth. Signals induced by IL-1beta and SDF-1alpha promoted the
      interaction of talin and paxillin with the cytoplasmic tails of integrin
      alpha4beta1, thereby stimulating myeloid cell adhesion to endothelium in vitro
      and in vivo. Inhibition of integrin-alpha4beta1, SDF-1alpha, or IL-1beta was
      sufficient to block tumor inflammation and growth, and the combined blockade of
      these molecules greatly accentuated these effects. Furthermore, antagonists of
      integrin-alpha4beta1 inhibited chemotherapy-induced tumor inflammation and acted
      synergistically with chemotherapeutic agents to suppress tumor inflammation and
      growth. These results show that targeting myeloid cell recruitment mechanisms can
      be an effective approach to suppress tumor progression.

PMID- 21948959
TI  - Symptoms, functional status and quality of life in patients with controlled and
      uncontrolled atrial fibrillation: data from the RealiseAF cross-sectional
      international registry.
AB  - BACKGROUND: Rate control and rhythm control are accepted management strategies
      for atrial fibrillation (AF). OBJECTIVE: RealiseAF aimed to describe the success
      of either strategy and the impact of control on symptomatic status of patients
      with AF. METHODS: This international, observational, cross-sectional survey of
      patients with any history of AF in the previous year, recorded AF
      characteristics, management and frequency of control (defined as sinus rhythm or
      AF with resting heart rate <=80 bpm). RESULTS: Overall, 9665 patients were
      evaluable for AF control, with 59.0% controlled (sinus rhythm 26.5%, AF <=80 bpm
      32.5%) and 41.0% uncontrolled. Symptom prevalence in the previous week was lower
      in controlled than uncontrolled AF (55.7% vs 68.4%; p<0.001) and similar for
      patients in sinus rhythm versus AF <=80 bpm (54.8% vs 56.4%; p=0.23). At the
      visit, AF-related functional impairment (EHRA class >I) was seen in 67.4% of
      patients with controlled AF and 82.1% of patients with uncontrolled AF (p<0.001).
      Quality-of-life (QoL, measured using EQ-5D) was better for patients with
      controlled versus uncontrolled AF using the Visual Analogue Scale (mean (SD)
      score 67.1 (18.4) vs 63.2 (18.9); p<0.001), single index utility score (median
      0.78 vs 0.73; p<0.001), or five dimensions of well-being (all p<0.001).
      Irrespective of AF control, cardiovascular events had led to hospitalisation in
      the past year in 28.1%. CONCLUSION: AF control is not optimal. Control appears to
      be associated with fewer symptoms and better QoL, but even patients with
      controlled AF have frequent symptoms, functional impairment, altered QoL and
      cardiovascular events. New treatments are needed to improve control and minimise
      the functional and QoL burden of AF.

PMID- 21948960
TI  - Almanac 2011: Cardiac arrhythmias and pacing. The national society journals
      present selected research that has driven recent advances in clinical cardiology.

PMID- 21948961
TI  - Almanac 2011: Acute coronary syndromes. The national society journals present
      selected research that has driven recent advances in clinical cardiology.

PMID- 21948963
TI  - Comparative in vitro activity of finafloxacin against staphylococci displaying
      normal and small colony variant phenotypes.
AB  - OBJECTIVES: Staphylococcal small colony variants (SCVs) are associated with
      chronic and relapsing infections and their intracellular location may shield them
      from host defences and antibiotics. Finafloxacin is a novel fluoroquinolone that
      exhibits optimal activity at slightly acidic conditions where the activity of
      other marketed fluoroquinolones decreases. Here, the in vitro activity of
      finafloxacin against clinical strain pairs consisting of an SCV and its clonally
      identical parental strain displaying the normal phenotype (NP) was compared with
      those of other fluoroquinolones at standard and low pH. METHODS: In vitro
      activities of finafloxacin, ciprofloxacin, levofloxacin and moxifloxacin were
      tested against 28 methicillin-susceptible Staphylococcus aureus (MSSA) and three
      methicillin-resistant S. aureus (MRSA) SCV-NP strain pairs. Additionally, two S.
      aureus mutants (DeltahemB and DeltathyA) displaying the SCV phenotype and their
      wild-type strains as well as four SCV-NP pairs of coagulase-negative
      staphylococcal (CoNS) strains were included. MIC(50,) MIC(90) and MIC ranges were
      calculated based on MIC determination by Etest((r)) at pH 5.8 and pH 7.2.
      RESULTS: Under acidic conditions, finafloxacin demonstrated superior activity
      against MSSA, MRSA and CoNS regardless of the phenotype. At neutral conditions,
      the activity against MSSA was as follows: moxifloxacin > finafloxacin >
      levofloxacin > ciprofloxacin. In comparison with methicillin-susceptible NP
      isolates, ciprofloxacin was less active against their corresponding SCVs. For
      other fluoroquinolones, there was no marked difference in activity against SCVs
      compared with NPs. CONCLUSIONS: Particularly in acidic body compartments,
      finafloxacin appears to be a promising new antibiotic for the treatment of
      persistent staphylococcal infections, including those caused by SCVs.

PMID- 21948962
TI  - Oral sildenafil treatment for Eisenmenger syndrome: a prospective, open-label,
      multicentre study.
AB  - BACKGROUND: Although sildenafil has been shown to be safe and effective in
      idiopathic pulmonary arterial hypertension (PAH) and PAH related to connective
      tissue disease, its effects in Eisenmenger syndrome are less clear. OBJECTIVE: To
      investigate whether long-term treatment (12 months) with the phosphodiesterase
      type 5 inhibitor sildenafil improves clinical and haemodynamic parameters in
      patients with Eisenmenger syndrome. DESIGN: Prospective, open-label, multicentre
      study. SETTING: Four pulmonary hypertension centres in China. PATIENTS: 84
      Eisenmenger syndrome functional class II-IV patients. INTERVENTIONS: Oral
      sildenafil 20 mg orally three times a day. OUTCOME MEASURES: 6-min walk distance
      (6MWD) test, resting systemic arterial blood oxygen saturation (SaO(2)) in room
      air, haemodynamic parameters assessed by right heart catheterisation, safety and
      tolerability. RESULTS: The overall treatment effects at 12 months versus baseline
      (mean changes with 95% CIs) were 56 m increase (42 to 69, p<0.0001) in 6MWD, and
      2.4% increase (1.8% to 2.9%, p<0.0001) in resting room air SaO(2). Improvements
      were also seen in mean pulmonary arterial pressure and pulmonary vascular
      resistance index (-4.7 mm Hg (-7.5 to -1.9), p=0.001; and -474 dyn*s*cm(-5)*m(2)
      (-634 to -314), p<0.0001, respectively). Sildenafil was well tolerated. Most
      adverse events were mild and transient, and occurred in the first 2 weeks of
      treatment. CONCLUSIONS: Twelve months of oral sildenafil treatment was well
      tolerated and appeared to improve exercise capacity, systemic arterial oxygen
      saturation and haemodynamic parameters in patients with Eisenmenger syndrome.

PMID- 21948964
TI  - Tuning of antibacterial activity of a cyclopropyl fluoroquinolone by variation of
      the substituent at position C-8.
AB  - OBJECTIVES: If substituted at position C-8 by a methoxy group, fluoroquinolones
      possess antibacterial efficacy considerably improved over that of C-H analogues.
      The new veterinary fluoroquinolone pradofloxacin bears a cyano group at C-8 and
      it was attempted to define the ranges of activity unfolding upon variation of
      this moiety. METHODS: Pradofloxacin and six analogues were subjected to MIC and
      mutant prevention concentration (MPC) analysis; we determined comparative
      activities against one wild-type and two isogenic first-step fluoroquinolone
      resistant variants each of Escherichia coli and Staphylococcus aureus.
      Ciprofloxacin, enrofloxacin and its 8-CN analogue, the R,R-pyrrolidinopiperidine
      enantiomer of pradofloxacin as well as the 8-OH congener of pradofloxacin served
      as references. RESULTS: MICs were of limited utility in resolving differences in
      antibacterial activity. Regarding MPCs, E. coli was inhibited most effectively by
      ciprofloxacin. However, pradofloxacin and analogues bearing Cl or F closely
      matched that activity. MPCs of O-alkyl and the R,R-pyrrolidinopiperidine
      substituted compounds indicated lower activities, while the 8-OH metabolite,
      essentially, had lost activity. Replacement of 8-H by CN, resulting in up to 7
      fold reduced MPCs, was a prerequisite for high activity against the wild-type
      strains and first-step fluoroquinolone-resistant variants. Narrowed mutant
      selection windows, observed for both variants of E. coli and wild-type S. aureus,
      indicated an improved potential of pradofloxacin for restricting the selection of
      clones with reduced susceptibility. CONCLUSIONS: Substitution of hydrogen at
      position C-8 of an analogue of pradofloxacin by CN provided for MPCs lower than
      those of 8-O-CH(3) and almost similar to C-8-halogenated compounds, while alkoxy
      substituents caused reduced activity and hydroxylation resulted in inactivation.
      Efficacy was co-dependent on the amine moiety located at C-7.

PMID- 21948965
TI  - A randomized, double-blind, placebo-controlled pilot study to assess the ability
      of rifaximin to prevent recurrent diarrhoea in patients with Clostridium
      difficile infection.
AB  - BACKGROUND: Uncontrolled case series have demonstrated decreased Clostridium
      difficile infection (CDI) recurrence in patients given rifaximin after standard
      antibiotic therapy. However, clinical trials assessing whether rifaximin
      decreases recurrent diarrhoea in patients with CDI have not been performed. The
      purpose of this study was to assess rates of recurrent diarrhoea in patients with
      CDI given rifaximin versus placebo immediately after standard therapy. METHODS:
      This was a randomized, double-blind, placebo-controlled pilot study. Patients
      with CDI and a Horn's index >=1 were randomized to receive rifaximin 400 mg three
      times daily or placebo for 20 days given immediately after finishing standard
      anti-CDI antibiotics. Patients were followed for 3 months and assessed for
      recurrent diarrhoea that included CDI recurrence (return of diarrhoea with a
      positive toxin test) and patient self-reported return of non-CDI diarrhoea after
      a period of wellness. RESULTS: Sixty-eight patients aged 61 +/- 18 years (50%
      male) were given rifaximin (n = 33) or placebo (n = 35). Twenty-four of 68 (35%)
      patients had recurrent diarrhoea either due to recurrent CDI (23.5%) or self
      reported diarrhoea (11.5%). Recurrent diarrhoea occurred in 17 of 35 (49%)
      patients given placebo and 7 of 33 (21%) given rifaximin (P = 0.018). CDI
      recurrence occurred in 11 of 35 (31%) patients given placebo and 5 of 33 (15%)
      patients given rifaximin (P = 0.11). Self-reported diarrhoea occurred in 6 of 35
      (17%) of patients given placebo and 2 of 33 (6%) given rifaximin (P = 0.15).
      CONCLUSIONS: Patients with CDI given a rifaximin chaser regimen experienced a
      decreased incidence of recurrent diarrhoea compared with placebo.

PMID- 21948966
TI  - Waves of trouble: MRSA strain dynamics and assessment of the impact of infection
      control.
AB  - There has been a sustained decline in bloodstream infections due to methicillin
      resistant Staphylococcus aureus (MRSA) throughout the UK. The UK MRSA epidemic,
      which began in the 1990s, has been dominated by two epidemic MRSA (EMRSA) clones
      {EMRSA-15, of clonal complex (CC) 22 [sequence type (ST) 22], and EMRSA-16, of
      CC30 (ST36)}. It appears that both these clones followed a wave trajectory
      (initial expansion, relative stasis, then decline). Three recent studies have
      shown that ST36 has declined faster than ST22, a change that appears to have
      begun before the recent intensification of intensive control measures in the UK.
      The biological basis of infectious disease waves, including those of MRSA, is
      discussed, as are the implications of such waves for the assessment of the impact
      of infection control measures.

PMID- 21948967
TI  - Metabolic signatures imaged in cancer-induced cachexia.
AB  - Cancer-induced cachexia is a complex and poorly understood life-threatening
      syndrome that is characterized by progressive weight loss due to metabolic
      alterations, depletion of lipid stores, and severe loss of skeletal muscle
      protein. Gaining the ability to noninvasively image the presence or onset of
      cachexia is important to better treat this condition, to improve the design and
      optimization of therapeutic strategies, and to detect the responses to such
      treatments. In this study, we employed noninvasive magnetic resonance
      spectroscopic imaging (MRSI) and [(18)F]fluoro-2-deoxy-D-glucose ((18)FDG)
      positron emission tomography (PET) to identify metabolic signatures typical of
      cachectic tumors, using this information to analyze the types and extents of
      metabolic changes induced by the onset of cachexia in normal tissues. Cachexia
      was confirmed by weight loss as well as analyses of muscle tissue and serum. In
      vivo, cachexia-inducing murine adenocarcinoma (MAC)16 tumors were characterized
      by higher total choline (tCho) and higher (18)FDG uptake than histologically
      similar noncachectic MAC13 tumors. A profound depletion of the lipid signal was
      observed in normal tissue of MAC16 tumor-bearing mice but not within the tumor
      tissue itself. High-resolution (1)H magnetic resonance spectroscopy (MRS)
      confirmed the high tCho level observed in cachectic tumors that occurred because
      of an increase of free choline and phosphocholine. Higher succinate and lower
      creatine levels were also detected in cachectic tumors. Taken together, these
      findings enhance our understanding of the effect of cancer on host organs and
      tissues as well as promote the development of noninvasive biomarkers for the
      presence of cachexia and identification of new therapeutic targets.

PMID- 21948968
TI  - MYB is essential for mammary tumorigenesis.
AB  - MYB oncogene upregulation is associated with estrogen receptor (ER)-positive
      breast cancer, but disease requirements for MYB function in vivo have not been
      explored. In this study, we provide evidence of a critical requirement for MYB
      functions in models of human and murine breast cancer. In human breast cancer, we
      found that MYB expression was critical for tumor cell growth both in vitro and in
      vivo in xenograft settings. In transgenic knockout mice, tissue-specific deletion
      of the murine MYB gene caused a transient defect in mammary gland development
      that was reflected in delayed ductal branching and defective apical bud
      formation. In mouse mammary tumor virus (MMTV)-NEU mice where tumors are
      initiated by activation of HER2, MYB deletion was sufficient to abolish tumor
      formation. In the more aggressive MMTV-PyMT model system, MYB deletion delayed
      tumorigenesis significantly. Together, the findings in these transgenic knockout
      models implied that MYB was critical during an early window in mammary
      development when it was essential for tumor initiation, even though MYB loss did
      not exert a lasting impact upon normal mammary function. Two important MYB-target
      genes that promote cell survival, BCL2 and GRP78/BIP, were each elevated compared
      with nontransformed mammary epithelial cells, thereby promoting survival as
      confirmed in colony formation assays in vitro. Taken together, our findings
      establish a role for MYB at the hub of ER- and HER2-dependent pathways in mammary
      carcinogenesis.

PMID- 21948969
TI  - Chemotherapy induces intratumoral expression of chemokines in cutaneous melanoma,
      favoring T-cell infiltration and tumor control.
AB  - T-cell infiltration is known to impact tumor growth and is associated with cancer
      patient survival. However, the molecular cues that favor T-cell infiltration
      remain largely undefined. Here, using a genetically engineered mouse model of
      melanoma, we show that CXCR3 ligands and CCL5 synergize to attract effector T
      cells into cutaneous metastases, and their expression inhibits tumor growth.
      Treatment of tumor-bearing mice with chemotherapy induced intratumoral expression
      of these chemokines and favored T-cell infiltration into cutaneous tumors. In
      patients with melanoma, these chemokines were also upregulated in chemotherapy
      sensitive lesions following chemotherapy, and correlated with T-cell
      infiltration, tumor control, and patient survival. We found that dacarbazine,
      temozolomide, and cisplatin induced expression of T-cell-attracting chemokines in
      several human melanoma cell lines in vitro. These data identify the induction of
      intratumoral expression of chemokines as a novel cell-extrinsic mechanism of
      action of chemotherapy that results in the recruitment of immune cells with
      antitumor activity. Therefore, identifying chemotherapeutic drugs able to induce
      the expression of T-cell-attracting chemokines in cancer cells may represent a
      novel strategy to improve the efficacy of cancer immunotherapy.

PMID- 21948970
TI  - AGR2 is a novel surface antigen that promotes the dissemination of pancreatic
      cancer cells through regulation of cathepsins B and D.
AB  - Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers
      largely due to disseminated disease at the time of presentation. Here, we
      investigated the role and mechanism of action of the metastasis-associated
      protein anterior gradient 2 (AGR2) in the pathogenesis of pancreatic cancer. AGR2
      was induced in all sporadic and familial pancreatic intraepithelial precursor
      lesions (PanIN), PDACs, circulating tumor cells, and metastases studied. Confocal
      microscopy and flow cytometric analyses indicated that AGR2 localized to the
      endoplasmic reticulum (ER) and the external surface of tumor cells. Furthermore,
      induction of AGR2 in tumor cells regulated the expression of several ER
      chaperones (PDI, CALU, RCN1), proteins of the ubiquitin-proteasome degradation
      pathway (HIP2, PSMB2, PSMA3, PSMC3, and PSMB4), and lysosomal proteases
      [cathepsin B (CTSB) and cathepsin D (CTSD)], in addition to promoting the
      secretion of the precursor form pro-CTSD. Importantly, the invasiveness of
      pancreatic cancer cells was proportional to the level of AGR2 expression.
      Functional downstream targets of the proinvasive activity of AGR2 included CTSB
      and CTSD in vitro, and AGR2, CTSB, and CTSD were essential for the dissemination
      of pancreatic cancer cells in vivo. Taken together, the results suggest that AGR2
      promotes dissemination of pancreatic cancer and that its cell surface targeting
      may permit new strategies for early detection as well as therapeutic management.

PMID- 21948971
TI  - Prevalence and predictors of coexistent silent atherosclerotic cardiovascular
      disease in patients with abdominal aortic aneurysm without previous symptomatic
      cardiovascular diseases.
AB  - Although patients with abdominal aortic aneurysm (AAA) often have other
      cardiovascular diseases (CVDs), the exact prevalence remains unclear. We aimed to
      determine the prevalence and predictors of coexistent silent atherosclerotic
      cardiovascular diseases (SACVDs) in patients with AAA without a history of CVD.
      Consecutive 157 patients with AAA (mean age, 73 years), without any previous
      history of CVD, were included. Silent myocardial ischemia (SMI), cerebrovascular
      disease (CeVD), peripheral artery disease (PAD), and thoracic aortic aneurysm
      (TAA) without symptoms coexisted in 29.3%, 25.5%, 15.9%, and 8.3%, respectively.
      The significant predictors of SMI were diabetes mellitus (P = .025) and male sex
      (P = .048). The significant predictor of silent CeVD was older age (P = .039).
      The borderline predictors of asymptomatic PAD and TAA were diabetes mellitus (P =
      .056) and AAA size (P = .053), respectively. Even with no previous symptomatic
      CVD, patients with AAA have high prevalence of coexistent SACVD.

PMID- 21948972
TI  - Increased carotid intima-media thickness is associated with higher SYNTAX score.
AB  - The main purpose of this study was to investigate the relation between carotid
      intima-media thickness (CIMT) and coronary artery disease (CAD) complexity.
      Consecutive patients (n = 360) with CAD confirmed by coronary angiography were
      enrolled. Mean CIMT and the overall SYNTAX score (SXscore) were 0.87 +/- 0.12 mm
      and 15 +/- 9, respectively. In univariate analysis, there was a significant
      correlation between the overall SXscore and CIMT (r = .42, P < .001), age (r =
      .23, P < .001), hypertension (r = .27, P = 0.001), diabetes (r = 0.11, P = 0.02),
      smoking (r = .24, P = .01), dyslipidemia (r = .2, P = 0.03), and beta-blocker use
      (r = .19, P < .001). In multivariate analysis, CIMT (beta = .34, P < .001) and
      age (beta = .11, P < .019) were independently associated with SXscore. We have
      demonstrated a significant relation between CIMT and SXscore. Although this study
      is correlative and no causative conclusions can be drawn, our findings suggest
      that increased CIMT could reflect complex coronary artery lesions.

PMID- 21948973
TI  - Platelet-activating factor and its basic metabolic enzymes in blood of naive HIV
      infected patients.
AB  - Platelet-activating factor (PAF), a mediator of proatherosclerotic inflammatory
      processes, is also implicated in endothelial dysfunction during human
      immunodeficiency virus (HIV) infection. We examined PAF metabolism in blood of
      naive male patients, 8 with early HIV infection (group A) and 17 just before
      treatment initiation (group B), versus 18 healthy age-matched males (group C).
      Statistical analysis was performed with 1-way analysis of variance (ANOVA)
      criterion and Pearson r test. Higher PAF biosynthesis in patients' leukocytes
      versus group C was accompanied by an increase in lipoprotein-associated
      phospholipase A2 (Lp-PLA2) activity that degrades PAF. Moreover, PAF synthesis
      was higher and Lp-PLA2 activity was lower in group B compared to group A.
      Lipoprotein-associated phospholipase A2 was positively correlated with viral load
      and negatively correlated with CD4 cell counts in group B. The activities of PAF
      basic biosynthetic enzymes in patients' leukocytes were also negatively
      correlated with CD4 cell counts. The observed continuous increase in PAF
      biosynthesis during HIV infection progress seems to amplify the risk of AIDS
      manifestations and/or cardiovascular complications in HIV-infected patients,
      while a subsequent increase in Lp-PLA2 activity seems to be a host response.

PMID- 21948974
TI  - The acute effects of passive smoking on mean platelet volume in healthy
      volunteers.
AB  - Mean platelet volume (MPV) is an indicator of platelet activation. We
      investigated the acute effect of passive smoking on MPV in healthy volunteers.
      Healthy nonsmoker volunteers (n = 90) spent 120 minutes in a smoke-free room.
      Then they were exposed to passive smoking in 3 groups consisting of 30 volunteers
      each in group A (carbon monoxide [CO] < 7.5 ppm), group B (CO = 7.5-15 ppm), and
      group C (CO > 15 ppm) for 120 minutes in a smoking room. Mean platelet volume did
      not change in group A and in the smoke-free room. Mean platelet volume increased
      significantly at the 60th minute and continued to increase at the 90th and 120th
      minute in group B. Mean platelet volume increased significantly at the 30th
      minute and continued to increase at the 60th, 90th, and 120th minute in group C.
      In conclusion, acute exposure to passive smoking affected MPV according to the
      duration and intensity of smoke.

PMID- 21948975
TI  - High levels of serum uric acid impair development of coronary collaterals in
      patients with acute coronary syndrome.
AB  - We evaluated the association of serum uric acid (SUA) level and development of
      coronary collateral vessels (CCVs) in patients with acute coronary syndrome
      (ACS). Patients (n = 224) with ACS were included in the study. Coronary
      collateral vessels were graded according to the Rentrop scoring system. Rentrop
      grade 0 was accepted as absence of CCV (group 1; n = 117) and Rentrop grade >=1
      was accepted as presence of CCV (group 2; n = 107). Rentrop 0-1 (poor CCV) were
      determined in 167 patients and Rentrop 2-3 (good CCV) were determined in 57
      patients. Both presence of CCV (P < .001) and development of good CCV (P = .003)
      were significantly associated with low levels of SUA. We suggest that high levels
      of SUA affect the CCV development negatively in nondiabetic and nonhypertensive
      patients with ACS.

PMID- 21948976
TI  - Cognitive components of social capital and mental health status among older
      adults: a population-based cross-sectional study.
AB  - AIMS: To determine the associations between the cognitive aspects of social
      capital and mental health status in older adults. METHODS: Data on older people
      (65 years of age or older, n = 1,102) were retrieved from a general population
      mental health survey conducted in Finland in 2008. The response rate was 61%. The
      associations between self-reported depression (measured by the Composite
      International Diagnostic Interview Short Form, CIDI-SF) or psychological distress
      (measured by the General Health Questionnaire, GHQ-12) and perceived social
      support, sense of belonging, and trust were tested by logistic regression
      analyses. RESULTS: For the cognitive social capital indicators, difficult access
      to help from neighbours showed a significant association with depression.
      Furthermore, not having people to count on, experiencing a lack of concern from
      other people, and feeling mistrust towards other people were all significantly
      associated with psychological distress. CONCLUSIONS: Links between mental health
      and cognitive social capital indicate that social support and trust may be
      important factors to consider when developing interventions to promote mental
      health and prevent mental disorders among older adults.

PMID- 21948977
TI  - Physical activity patterns in Greenland: a country in transition.
AB  - AIMS: To examine differences in physical activity patterns among Inuit in
      Greenland in relation to social transition. The Inuit in Greenland are an
      indigenous population in the circumpolar north who are experiencing rapid social
      transition. METHODS: Physical activity patterns were assessed by the
      International Physical Activity Questionnaire (long version). The population was
      divided into six groups according to different stages of social change, measured
      on the basis of education, current residence and occupation. Data were collected
      in a country-wide cross-sectional population survey among adult Inuit in
      Greenland from 2005 to 2009. RESULTS: Men with long vocational or academic
      education living in towns (latest stage of social change) spent significantly
      less time on occupational physical activity (p = 0.001) compared with hunters and
      fishermen in villages (earliest stage of social change) (trend test p = 0.01).
      Women in the latest stage of change spent significantly less time on domestic
      physical activity (p < 0.001) (trend test p = 0.06) compared with women in the
      earliest stage of social change. This was also found for physical activity during
      transportation (p = 0.02 and p = 0.01 for men and women, respectively). No
      significant difference was found for leisure time physical activity. Men and
      women in the latest stage of social change spent more time on sedentary activity
      (p < 0.001). CONCLUSIONS: Differences in physical activity patterns among Inuit
      in Greenland included decreasing time spent on domestic and occupational physical
      activity and increasing time spent on sedentary activities along with social
      change. Knowledge of changes in physical activity patterns in relation to social
      transition is important in prevention of obesity, type 2 diabetes and lifestyle
      diseases.

PMID- 21948978
TI  - Why the concept ''lifestyle diseases'' should be avoided.
AB  - The concept lifestyle disease is used about a number of different diseases such
      as coronary heart disease, diabetes, lung cancer etc. The concept indicates that
      people's behaviours cause the diseases. This is only partly true. All diseases,
      both so-called lifestyle diseases and infectious diseases, have multiple causes.
      Singling out only one type of causes, such as is implied in the concept of
      lifestyle diseases can lead prevention to focus only on changing people s
      behaviours or lifestyles, and thus to neglect other possibilities to improve
      health. Mortality due to chronic diseases has increased during the last century
      and the main cause behind this is the decrease in the mortality in infectious
      diseases among younger people. More people live long enough to develop the
      chronic diseases. The concept lifestyle disease gives a too narrow picture of
      causes death and should be abandoned and give place for a broader understanding
      of causes and preventive options.

PMID- 21948979
TI  - Respondent-driven sampling to recruit in-country migrant workers in China: a
      methodological assessment.
AB  - AIM: Respondent-driven Sampling (RDS) is a new form of chain-referral sampling,
      which is superior to random sampling and traditional non-probability sampling in
      hard-to-reach populations. We employed RDS to recruit internal migrant workers in
      Chengdu, Sichuan Province, China, and examined whether it could be successfully
      used in this population. METHODS: 1,270 migrant workers were recruited into the
      study. Social demographic information, social network size, and geographic
      information about participants' residential locations were collected. RDSAT
      software and geographic information system (GIS) technology were used to examine
      whether RDS was successful. RESULTS: The results showed that the sample
      compositions converged to equilibrium very quickly. Sample representativeness
      testing results showed that females (t = 3.61, p < 0.001) and people aged 46
      years old and above (t = 3.222, p < 0.001) were under-represented. GIS results
      showed that respondents were concentrated in the vicinity of the third road ring
      of Chengdu, especially in the areas of 3, 4 and 21, which were close to the
      investigation site. CONCLUSIONS: The results demonstrated that RDS is a robust
      sampling method in the study of migrant workers. Despite its potential utility,
      it is also important to recognize and mitigate potential limitations, such as
      geographic proximity.

PMID- 21948980
TI  - Polyphenol-rich sweet potato greens extract inhibits proliferation and induces
      apoptosis in prostate cancer cells in vitro and in vivo.
AB  - Sweet potato (Ipomoea batatas) leaves or greens, extensively consumed as a
      vegetable in Africa and Asia, are an excellent source of dietary polyphenols such
      as anthocyanins and phenolic acids. Here, we show that sweet potato greens
      extract (SPGE) has the maximum polyphenol content compared with several
      commercial vegetables including spinach. The polyphenol-rich SPGE exerts
      significant antiproliferative activity in a panel of prostate cancer cell lines
      while sparing normal prostate epithelial cells. Mechanistically, SPGE perturbed
      cell cycle progression, reduced clonogenic survival, modulated cell cycle and
      apoptosis regulatory molecules and induced apoptosis in human prostate cancer PC
      3 cells both in vitro and in vivo. SPGE-induced apoptosis has a mitochondrially
      mediated component, which was attenuated by pretreatment with cyclosporin A. We
      also observed alterations of apoptosis regulatory molecules such as inactivation
      of Bcl2, upregulation of BAX, cytochrome c release and activation of downstream
      apoptotic signaling. SPGE caused DNA degradation as evident by terminal
      deoxynucleotidyl transferase-mediated dUTP-nick-end labeling (TUNEL) staining of
      increased concentration of 3'-DNA ends. Furthermore, apoptotic induction was
      caspase dependent as shown by cleavage of caspase substrate, poly (adenosine
      diphosphate-ribose) polymerase. Oral administration of 400 mg/kg SPGE remarkably
      inhibited growth and progression of prostate tumor xenografts by ~69% in nude
      mice, as shown by tumor volume measurements and non-invasive real-time
      bioluminescent imaging. Most importantly, SPGE did not cause any detectable
      toxicity to rapidly dividing normal tissues such as gut and bone marrow. This is
      the first report to demonstrate the in vitro and in vivo anticancer activity of
      sweet potato greens in prostate cancer.

PMID- 21948981
TI  - Elf3 regulates allergic airway inflammation by controlling dendritic cell-driven
      T cell differentiation.
AB  - Elf3 belongs to the Ets family of transcription factors and has been implicated
      in inflammation. Elf3 is highly expressed in the lungs, and Elf3(-/-) mice are
      impaired in IL-6 production after intranasal LPS exposure. To identify the role
      of Elf3 in Th17-driven pulmonary inflammation, we have performed epicutaneous
      sensitization of Elf3(-/-) mice with OVA followed by airway OVA challenge and
      have identified Elf3(-/-) mice to be impaired in induction of Th17 response,
      attributable to impairment of IL-6 production by dendritic cells (DCs). However,
      increased serum levels of OVA-specific IgG1 and IgE were observed, pointing
      toward an exaggerated Th2 response. To study Th2 response, we performed i.p.
      sensitization of Elf3(-/-) mice with OVA and confirmed loss of Elf3 to result in
      an aggravated Th2 response, characterized by increased generation of IL-4
      producing T cells, increased levels of OVA-specific IgE and IgG1 Ab titers, and
      increased serum levels of Th2 cytokines, together with extensive inflammation and
      mucus production in airways. Elf3(-/-) DCs were impaired in priming Th1
      differentiation, which, in turn, promoted Th2 differentiation. This was mediated
      by the ability of Elf3(-/-) DCs to undergo hypermaturation but secrete
      significantly lower levels of IL-12 in response to inflammatory stimuli. The
      impairment of IL-12 production was due to impairment of IL-12p40 gene induction
      in Elf3(-/-) DCs in response to inflammatory stimuli. Taken together, our study
      identifies a novel function of Elf3 in regulating allergic airway inflammation by
      regulating DC-driven Th1, Th2, and Th17 differentiation.

PMID- 21948982
TI  - Cutting edge: expression of XCR1 defines mouse lymphoid-tissue resident and
      migratory dendritic cells of the CD8alpha+ type.
AB  - Subsets of dendritic cells (DCs) have been described according to their functions
      and anatomical locations. Conventional DC subsets are defined by reciprocal
      expression of CD11b and CD8alpha in lymphoid tissues (LT), and of CD11b and CD103
      in non-LT (NLT). Spleen CD8alpha(+) and dermal CD103(+) DCs share a high
      efficiency for Ag cross-presentation and a developmental dependency on specific
      transcription factors. However, it is not known whether all NLT-derived CD103(+)
      DCs and LT-resident CD8alpha(+) DCs are similar despite their different
      anatomical locations. XCR1 was previously described as exclusively expressed on
      mouse spleen CD8alpha(+) DCs and human blood BDCA3(+) DCs. In this article, we
      showed that LT-resident CD8alpha(+) DCs and NLT-derived CD103(+) DCs specifically
      express XCR1 and are characterized by a unique transcriptional fingerprint,
      irrespective of their tissue of origin. Therefore, CD8alpha(+) DCs and CD103(+)
      DCs belong to a common DC subset which is unequivocally identified by XCR1
      expression throughout the body.

PMID- 21948983
TI  - Invariant NKT cell defects in vitamin D receptor knockout mice prevents
      experimental lung inflammation.
AB  - Vitamin D receptor (VDR) deficiency (knockout [KO]) results in a failure of mice
      to generate an airway hyperreactivity (AHR) response on both the BALB/c and
      C57BL/6 background. The cause of the failed AHR response is the defective
      population of invariant NKT (iNKT) cells in the VDR KO mice because wild-type
      (WT) iNKT cells rescued the AHR response. VDR KO mice had significantly fewer
      iNKT cells and normal numbers of T cells in the spleen compared with WT mice. In
      BALB/c VDR KO mice, the reduced frequencies of iNKT cells were not apparent in
      the liver or thymus. VDR KO and WT Th2 cells produced similar levels of IFN-gamma
      and IL-5. On the BALB/c background, Th2 cells from VDR KO mice produced less IL
      13, whereas on the C57BL/6 background, Th2 cells from VDR KO mice produced less
      IL-4. Conversely, VDR KO iNKT cells were defective for the production of multiple
      cytokines (BALB/c: IL-4, IL-5, and IL-13; C57BL/6: IL-4 and IL-17). Despite
      relatively normal Th2 responses, BALB/c and C57BL/6 VDR KO mice failed to develop
      AHR responses. The defect in iNKT cells as a result of the VDR KO was more
      important than the highly susceptible Th2 background of the BALB/c mice.
      Defective iNKT cell responses in the absence of the VDR result in the failure to
      generate AHR responses in the lung. The implication of these mechanistic findings
      for human asthma requires further investigation.

PMID- 21948984
TI  - EBI2 operates independently of but in cooperation with CXCR5 and CCR7 to direct B
      cell migration and organization in follicles and the germinal center.
AB  - Migration of B cells within lymphoid follicles is controlled by the chemokine
      receptors CXCR5 and CCR7 and the G-protein-coupled receptor EBI2 (GPR183).
      Whereas CXCR5 and CCR7 are known to mediate migration toward their respective
      chemokine ligands, it is unclear whether EBI2 acts by modulating these processes
      or by directly mediating chemotaxis toward its own spatially restricted ligand.
      It is also unknown how signals from these three receptors are integrated to
      control B cell localization. To answer these questions, we generated compound
      knockout mice deficient in expression of EBI2, CXCR5, or CCR7. Analysis of these
      mice revealed that EBI2 mediates B cell migration toward the outer areas of
      follicles and to bridging channels of the spleen independent of both CXCR5 and
      CCR7. Migratory signals delivered by EBI2 were shown to control B cell
      organization within the spleen and to be particularly important for positioning
      activated B cells in the early stages of Ab responses. An additional minor role
      for EBI2 was identified in the organization and affinity maturation of B cells in
      germinal centers. Thus, EBI2-mediated chemotaxis provides a third dimension to B
      cell migration that balances and integrates with the inputs from CXCR5 and CCR7
      to determine B cell positioning.

PMID- 21948986
TI  - Acid sphingomyelinase is required for protection of effector memory T cells
      against glucocorticoid-induced cell death.
AB  - The activity of acid sphingomyelinase (aSMase) was previously reported to be
      involved in glucocorticoid-induced cell death (GICD) of T lymphocytes. This
      mechanism in turn is believed to contribute to the therapeutic efficacy of
      glucocorticoids (GCs) in the treatment of inflammatory diseases. In this study,
      we reassessed the role of aSMase in GICD by using aSMase knockout mice. The
      absence of aSMase largely abolished the partial protection that effector memory
      CD4(+) T cells in wild-type mice possess against GICD. Reduced IL-2 secretion by
      aSMase-deficient CD4(+) T cells suggested that a lack of this important survival
      factor might be the cause of these cells' enhanced susceptibility to GICD.
      Indeed, addition of IL-2 restored the protection against GICD, whereas
      neutralization of IL-2 abrogated the otherwise protective effect seen in wild
      type effector memory CD4(+) T cells. The therapeutic implications of the altered
      sensitivity of aSMase-deficient T cells to GICD were assessed in models of
      inflammatory disorders; namely, experimental autoimmune encephalomyelitis and
      acute graft-versus-host disease. Surprisingly, GC treatment was equally efficient
      in both models in terms of ameliorating the diseases, regardless of the genotype
      of the T cells. Thus, our data reveal a hitherto unrecognized contribution of
      aSMase to the sensitivity of effector memory CD4(+) T cells to GICD and call into
      question the traditionally attributed importance of GICD of T cells to the
      treatment of inflammatory diseases by GCs.

PMID- 21948985
TI  - B cell depletion enhances T regulatory cell activity essential in the suppression
      of arthritis.
AB  - The efficacy of B cell-depletion therapy in rheumatoid arthritis has driven
      interest in understanding the mechanism. Because the decrease in autoantibodies
      in rheumatoid arthritis does not necessarily correlate with clinical outcome,
      other mechanisms may be operative. We previously reported that in proteoglycan
      induced arthritis (PGIA), B cell-depletion inhibits autoreactive T cell
      responses. Recent studies in B cell-depletion therapy also indicate a role for B
      cells in suppressing regulatory mechanisms. In this study, we demonstrate that B
      cells inhibited both the expansion and function of T regulatory (Treg) cells in
      PGIA. Using an anti-CD20 mAb, we depleted B cells from mice with PGIA and
      assessed the Treg cell population. Compared to control Ab-treated mice, Treg cell
      percentages were elevated in B cell-depleted mice, with a higher proportion of
      CD4(+) T cells expressing Foxp3 and CD25. On a per-cell basis, CD4(+)CD25(+)
      cells from B cell-depleted mice expressed increased amounts of Foxp3 and were
      significantly more suppressive than those from control Ab-treated mice. The
      depletion of Treg cells with an anti-CD25 mAb concurrent with B cell-depletion
      therapy restored the severity of PGIA to levels equal to untreated mice. Although
      titers of autoantibodies did not recover to untreated levels, CD4(+) T cell
      recall responses to the immunizing Ag returned as measured by T cell
      proliferation and cytokine production. Thus, B cells have the capacity to
      regulate inflammatory responses by enhancing effector T cells along with
      suppressing Treg cells.

PMID- 21948987
TI  - Sirtuin 1 promotes Th2 responses and airway allergy by repressing peroxisome
      proliferator-activated receptor-gamma activity in dendritic cells.
AB  - Sirtuins are a unique class of NAD(+)-dependent deacetylases that regulate
      diverse biological functions such as aging, metabolism, and stress resistance.
      Recently, it has been shown that sirtuins may have anti-inflammatory activities
      by inhibiting proinflammatory transcription factors such as NF-kappaB. In
      contrast, we report in this study that pharmacological inhibition of sirtuins
      dampens adaptive Th2 responses and subsequent allergic inflammation by
      interfering with lung dendritic cell (DC) function in a mouse model of airway
      allergy. Using genetic engineering, we demonstrate that sirtuin 1 represses the
      activity of the nuclear receptor peroxisome proliferator-activated receptor-gamma
      in DCs, thereby favoring their maturation toward a pro-Th2 phenotype. This study
      reveals a previously unappreciated function of sirtuin 1 in the regulation of DC
      function and Th2 responses, thus shedding new light on our current knowledge on
      the regulation of inflammatory processes by sirtuins.

PMID- 21948990
TI  - Ernst Kris: the objects of memory.
AB  - In 1956, the year before his death, Ernst Kris published a trilogy of papers on
      memory--"The Personal Myth," "On Some Vicissitudes of Insight in Psychoanalysis,"
      and "The Recovery of Childhood Memories"--and was planning to publish a monograph
      on the subject. In his papers on memory, by juxtaposing his clinical work with
      adult patients and his research on very young children, Kris sketched a
      trajectory of the dynamic relationship between preoedipal ego development and
      object relations, against the backdrop of psychosexual stages and the defenses
      that mediate memory. Kris was firmly committed to the premise that "the
      development of ego functions and object relations . . . are of equal and
      intrinsic importance." This paper explores how Kris's papers on memory may also
      be read as delineating his thinking on the role of object relations in infants
      and young children. In his last paper, the posthumously published "Decline and
      Recovery in the Life of a Three-Year-Old" (1962), his interest in ego development
      and object relations shifts to object relations, but the role of memory remains
      crucial. The paper concludes with some observations about the omissions and
      distortions that characterize how the history of psychoanalysis is recalled,
      orally transmitted, and written.

PMID- 21948988
TI  - Modeling of influenza-specific CD8+ T cells during the primary response indicates
      that the spleen is a major source of effectors.
AB  - The biological parameters that determine the distribution of virus-specific
      CD8(+) T cells during influenza infection are not all directly measurable by
      experimental techniques but can be inferred through mathematical modeling.
      Mechanistic and semimechanistic ordinary differential equations were developed to
      describe the expansion, trafficking, and disappearance of activated virus
      specific CD8(+) T cells in lymph nodes, spleens, and lungs of mice during primary
      influenza A infection. An intensive sampling of virus-specific CD8(+) T cells
      from these three compartments was used to inform the models. Rigorous statistical
      fitting of the models to the experimental data allowed estimation of important
      biological parameters. Although the draining lymph node is the first tissue in
      which Ag-specific CD8(+) T cells are detected, it was found that the spleen
      contributes the greatest number of effector CD8(+) T cells to the lung, with
      rates of expansion and migration that exceeded those of the draining lymph node.
      In addition, models that were based on the number and kinetics of professional
      APCs fit the data better than those based on viral load, suggesting that the
      immune response is limited by Ag presentation rather than the amount of virus.
      Modeling also suggests that loss of effector T cells from the lung is significant
      and time dependent, increasing toward the end of the acute response. Together,
      these efforts provide a better understanding of the primary CD8(+) T cell
      response to influenza infection, changing the view that the spleen plays a minor
      role in the primary immune response.

PMID- 21948991
TI  - Psychosocial problems in childhood and later alcohol consumption: a life course
      approach with historical information.
AB  - AIMS: Childhood psychosocial problems have been associated with poor alcohol
      habits in adulthood. The purpose of this study was to investigate further the
      association in men by using information from historical health records. METHODS:
      As part of the epidemiological FinDrink Study, we examined the association
      between childhood psychosocial problems and total ethanol consumption, binge
      drinking, and abstinence in later life among Finnish men. The participants were a
      sample from the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD), a
      population-based cohort study in eastern Finland. The data on childhood
      psychosocial factors were collected from health records (n = 952, 35.5% of the
      entire study sample), mainly from the 1930s to the 1950s. Questionnaire data on
      alcohol consumption were obtained from the baseline examinations of the KIHD
      cohort in 1984-1989. RESULTS: Controlling for age and examination year, the men
      who had been considered psychosocially disadvantaged by elementary school nurses
      had a 2.72-fold (95% confidence interval 1.30-5.65) risk of bingeing on fortified
      wine in later life. After adjustment for adulthood behavioural and socioeconomic
      factors the association (odds ratio 3.71, 95% confidence interval 1.56-8.84)
      appeared even stronger. Childhood psychosocial problems also contributed to
      abstinence, but did not appear to increase the total amount of ethanol consumed.
      CONCLUSIONS: Psychosocial problems observed in boys seem to contribute to
      different alcohol habits in later life. However, the factors eventually involved
      in the manifestation of problematic drinking patterns through the life course
      still require further research.

PMID- 21948992
TI  - Children's weight and participation in organized sports.
AB  - AIMS: Literature dealing with the impact of organized sports on children's weight
      has been marked by a lack of consensus. A major weakness characterizing most of
      this research is a lack of proper measurement methods. This paper seeks to fill
      an important knowledge gap through careful application of econometric methods.
      METHODS: Estimations are carried out using data on 1,400 children attending 6th
      grade in 2008 in the municipality of Aalborg, Denmark. We use standard ordinary
      least squares (OLS) and class fixed effects to explore the effect of sports
      participation on body mass index (BMI) as well as underweight, overweight and
      obesity. RESULTS: Results indicate that participation in organized sports reduced
      BMI by 2.1%. Likewise it reduced the likelihood of being overweight by 8.2
      percentage points and obese by 3.1 percentage points. CONCLUSIONS: It is the
      unique dataset combined with econometric methods that distinguishes our
      contribution from that of others in the field, thereby offering new insight.
      Results using statistically sound methods suggest that participation in organized
      sports has a beneficial effect on children's weight.

PMID- 21948993
TI  - Type D personality, depressive symptoms and work-related health outcomes.
AB  - AIMS: Personality may play a decisive role in perceiving work-related
      characteristics as stressful, leading to adverse health outcomes. Persons with a
      Distressed personality (Type D) experience increased negative emotions while
      inhibiting these emotions in social situations. We investigated the role of Type
      D personality on adverse health outcomes, sick leave, burnout and disability
      pension. The mediating role of depressive symptoms on this relation was assessed
      because Type D represents a vulnerability factor for depression. METHODS: In a
      cross-sectional community sample of the Dutch population (n = 1,172) Type D
      personality was related to sick-leave (five categories of days per year),
      burnout, and disability pension, controlling for confounders. RESULTS:
      Individuals with Type D personality reported more burnout (27% vs 8%), disability
      pension (32% vs 11%), and had an increased incidence of short-term sick leave
      (chi(2 )= 13.1, p = 0.011) as compared to non-Type D's. Type D was significantly
      related to burnout (odds ratio (OR) = 4.16) and disability pension (OR = 2.62)
      independent of confounders. The Sobel test indicated significant mediation of
      depression on the relation between Type D personality and the work-related health
      outcomes. After mediation Type D personality remained significantly related to
      burnout, indicating a unique unshared effect. CONCLUSIONS: Type D personality is
      related to adverse health outcomes in the working population, mediated by
      depression, which warrants further research for this personality type.

PMID- 21948994
TI  - Older people's perception of and coping with falling, and their motivation for
      fall-prevention programmes.
AB  - AIMS: This study aims to investigate older people's perceptions of and coping
      with falls, and what motivates them to join such programmes. METHOD: We used semi
      structured interviews to collect data on 14 individuals (65 years +) who
      contacted an emergency department because they had fallen. Data were analyzed
      using a phenomenographic approach that traces older people's perception of the
      phenomenon of ''falling''. RESULTS: Five categories and 15 subcategories emerged
      from the interviews. The five main categories were: emotional perceptions of
      falling; falling has consequences; coping with the situation; support from the
      social network; motivation and demotivation. To fall was shameful and
      embarrassing and could be explained by old age. To some, ''fear of falling'' was
      the dominant feeling. These people did not see falls as a risk factor they ought
      to care about. Instead, to prevent future falls, they restricted their activities
      or stopped certain activities altogether. If demands exceeded their resources,
      they asked their relatives or their general practitioner for help. Elderly people
      were motivated by autonomy, competence, and relatedness and preferred activities
      that spread happiness and joy, preferably in a social atmosphere, but they
      encountered elements in their surroundings that curbed their motivation.
      CONCLUSIONS: Future fall-prevention programmes must target older people's needs
      and acknowledge that there are many ways of perceiving falling. Moreover, elderly
      individuals' coping strategies are not necessarily productive. Social networks
      and general practitioners can actively encourage older people to participate in
      fall-prevention programmes. Such programmes must support older people's need for
      autonomy, competence and social relations.

PMID- 21948995
TI  - Equitable access to elective hospital services: the introduction of patient
      choice in a decentralised healthcare system.
AB  - AIM: During the 1980s and 1990s, increased waiting times for elective surgery was
      perceived to be a major accessibility problem in many countries. In an attempt to
      improve access, hospital choice reforms were introduced in a number of countries.
      In Norway, a nationwide reform to improve access came into effect in 2001. At the
      same time, renewed support was expressed for the long-standing political aim of
      ensuring equal access to healthcare services for all citizens regardless of their
      social position. The current aim is to analyse the relationship of the hospital
      choice reform and the goal of equitable access to hospital services. METHOD: A
      survey conducted among Norwegian patients in 2004 provided information about
      whether a choice of hospital had been made. Information from the survey was
      merged with administrative data from the hospital that performed the treatment.
      The survey provided data on patients' socioeconomic position. Demographics,
      medical need, and prior use of healthcare services were controlled for to
      determine the effect of socioeconomic position on hospital choice. RESULTS: The
      patient's socioeconomic position, measured by education, was found to be
      significantly associated with hospital choice. The relationship resembled that of
      a social gradient. Patients with a primary education were less likely to have
      made a choice, followed by those with secondary education or a lower university
      degree. Patients with higher university education were most likely to have
      chosen. CONCLUSIONS: Hospital selection is a demanding task for many patients.
      Policymakers should therefore focus on crafting and implementing tools necessary
      for supporting uptake of choice in disadvantaged groups.

PMID- 21948996
TI  - Will they stay fit and healthy? A three-year follow-up evaluation of a physical
      activity and health intervention in Polish youth.
AB  - AIMS: In this paper we evaluate the sustainability of changes of involvement in
      physical activity. The paper examines the effectiveness of a model aiming at
      influencing the frequency of leisure time physical activity, physical fitness and
      body constituency in youth. METHODS: The baseline of this study was a randomly
      selected sample of 13 year olds who participated in an intervention programme
      carried out in three schools in Poznan in 2005-08. From a total of 199 adolescent
      boys a subsample of 38 individuals from the experimental group and 34 from the
      control group were followed for 15 months after the interventional programme
      finished. From 170 girls, a subsample of 33 from the experimental group and 32
      girls from the control group were also randomly selected for the follow-up study.
      Among the variables monitored were: physical fitness, body constituency, and
      frequency of leisure time physical activity. All the variables were monitored in
      pre-test, post-test and follow-up examinations. RESULTS: It was established that
      15 months after the end of the interventional programme boys and girls from the
      intervention groups maintained a higher level of leisure time physical activity
      than their control group peers, and similarly in the case of selected health
      related components of physical fitness. No distinctive differences were found in
      the case of body constituency, though, apart from muscle mass and the sum of
      skinfolds in girls. CONCLUSIONS: The study exposed an increase in leisure time
      physical activity in time and a positive influence on selected components of
      health-related variables. The findings confirm the effectiveness of a multi-level
      intervention programme involving self-determined out-of-school physical activity
      planning for school-age youths, indicating the importance of personal and social
      context.

PMID- 21948997
TI  - Model-based approaches to synthesize microarray data: a unifying review using
      mixture of SEMs.
AB  - Several statistical methods are nowadays available for the analysis of gene
      expression data recorded through microarray technology. In this article, we take
      a closer look at several Gaussian mixture models which have recently been
      proposed to model gene expression data. It can be shown that these are special
      cases of a more general model, called the mixture of structural equation models
      (mixture of SEMs), which has been developed in psychometrics. This model combines
      mixture modelling and SEMs by assuming that component-specific means and
      variances are subject to a SEM. The connection with SEM is useful for at least
      two reasons: (1) it shows the basic assumptions of existing methods more
      explicitly and (2) it helps in straightforward development of alternative mixture
      models for gene expression data with alternative mean/covariance structures.
      Different specifications of mixture of SEMs for clustering gene expression data
      are illustrated using two benchmark datasets. 

PMID- 21948998
TI  - Fatty acids, obesity, and insulin resistance: time for a reevaluation.

PMID- 21948999
TI  - The complex mechanism of glutamate dehydrogenase in insulin secretion.

PMID- 21949002
TI  - Quantitative autism traits in first degree relatives: evidence for the broader
      autism phenotype in fathers, but not in mothers and siblings.
AB  - Autism spectrum disorder (ASD) symptoms are present in unaffected relatives and
      individuals from the general population. Results are inconclusive, however, on
      whether unaffected relatives have higher levels of quantitative autism traits
      (QAT) or not. This might be due to differences in research populations, because
      behavioral data and molecular genetic research suggest that the genetic etiology
      of ASD is different in multiplex and simplex families. We compared 117 unaffected
      siblings and 276 parents of at least one child with ASD with 280 children and 595
      adults from the general population on the presence of QAT using the Social
      Responsiveness Scale (SRS). Mean SRS scores for siblings, control children,
      parents and control adults were 25.4, 26.6, 33.7 and 32.9. Fathers of children
      with ASD showed significantly higher levels of QAT than controls, but siblings
      and mothers did not. We could not detect a statistically significant difference
      in SRS scores between relatives from simplex and multiplex families. These
      results do not support the theory of differential (genetic) etiology in multiplex
      and simplex families and suggest that a carried genetic risk is generally not
      expressed phenotypically in most relatives, except in fathers.

PMID- 21949000
TI  - ID'ing a novel inhibitor of beta-cell function, Id1.

PMID- 21949003
TI  - A retrospective chart study: the pathway to a diagnosis for adults referred for
      ASD assessment.
AB  - Charts of 125 adults (18 to 82 years), referred to an autism expert team for
      Autism Spectrum Disorder (ASD) assessment, were reviewed to explore the pathway
      to an adulthood ASD diagnosis. The participants first contacted the mental health
      care clinic at a median age of 19 years (range 2 to 78 years). Men contacted the
      clinic slightly earlier than women. The main referral reasons were social
      problems, feelings of anxiety and mood disturbances. The most common earlier
      diagnoses were anxiety and mood disorders or psychosis-related disorders. These
      diagnoses were more common in women than in men. Surprisingly few differences
      emerged between those who finally received an ASD diagnosis and those who did
      not. However, those with an ASD diagnosis contacted the clinic a mean of 15 years
      earlier and less frequently received different former diagnoses, although the
      type of diagnoses did not differ. The diagnostic criteria that were prevalent
      during early childhood of these adults did not influence their diagnostic
      history. A quarter of these clients were known with social problems within the
      mental health care system, but ASD was not assessed. Hence, the current study
      shows that the pathways to an adulthood ASD diagnosis are very heterogeneous.

PMID- 21949004
TI  - Motor proficiency and emotional/behavioural disturbance in autism and Asperger's
      disorder: another piece of the neurological puzzle?
AB  - The relationship of motor proficiency with emotional/behavioural disturbance,
      autistic symptoms and communication disturbance was investigated in children
      diagnosed with autism and Asperger's disorder (AD). The Movement Assessment
      Battery for Children was used as a measure of motor impairment, and the
      Developmental Behavioural Checklist was used as a measure of
      emotional/behavioural disturbance in the following groups: AD (n = 22), high
      functioning autism (HFA) (n = 23), LFA (n = 8) and typically developing children
      (n = 20). The HFA group had more difficulty with motor items, such as ball skills
      and balance, than did the AD group. There were significant positive correlations
      between impairments in motor proficiency (in particular ball skills and balance)
      and emotional/behavioural disturbance, autistic symptoms and communication
      disturbance. These findings are consistent with the hypothesis that there are
      qualitative and quantitative differences in the motor profile between autism and
      AD. In addition, the association between motor proficiency impairment and
      emotional/behavioural disturbance in autism and AD emphasizes the importance for
      screening of co-occurring emotional/behavioural symptoms in individuals with
      motor difficulties. These findings have implications for the potential use of
      adjunct motor measures in the diagnosis and definition of autism spectrum
      disorders.

PMID- 21949005
TI  - Learning through interaction in children with autism: preliminary data from
      asocial-communication-based intervention.
AB  - The study evaluates a social-communication-based approach to autism intervention
      aimed at improving the social interaction skills of children with autism spectrum
      disorder. We report preliminary results from an ongoing randomized controlled
      trial of 51 children aged 2 years 0 months to 4 years 11 months. Participants
      were assigned to either a target treatment or community treatment group. Families
      in the target treatment group were given 2 hours of therapy and coaching each
      week in an intervention emphasizing social-interaction and the parent-child
      relationship. Children in the community treatment group received a variety of
      services averaging 3.9 hours per week. After 12 months, outcomes were measured to
      determine changes in the groups in social interaction and communication. In
      addition, a regression analysis was conducted to determine whether changes in
      social interaction skills were associated with language development. Results
      suggest that children in the treatment group made significantly greater gains in
      social interaction skills in comparison to the community treatment group, but no
      between-group differences were found for standard language assessments.
      Initiation of joint attention, involvement, and severity of language delay were
      found to be significantly associated with improvement of language skills in
      children with autism. Finally caregiver skills targeted by the intervention were
      found to be significantly associated with changes in children's interaction
      skills.

PMID- 21949006
TI  - Sense making and benefit finding in couples who have a child with Asperger
      syndrome: an application of the Actor-Partner Interdependence Model.
AB  - Parents of children with Asperger syndrome face many challenges that may lead
      them to search for meaning by developing explanations for (sense making) and
      finding benefits (benefit finding) in having a child with special needs. Although
      family theorists have proposed that finding meaning occurs interpersonally, there
      is a dearth of empirical research that has examined finding meaning at the couple
      level. This study examined sense making and benefit finding in 84 couples who
      have a child with Asperger syndrome by using the Actor-Partner Interdependence
      Model (Kenny et al., 2006) to examine actor effects (i.e. the extent to which an
      individual's score on the predictor variable impacts his or her own level of
      adjustment) and partner effects (i.e. the extent to which an individual's score
      on the predictor variable has an impact on his or her partner's level of
      adjustment) of sense making and benefit finding on parental adjustment. Results
      demonstrated that parents' benefit finding related to greater anxiety and
      parents' sense making related to not only their own adjustment but also their
      partner's adjustment. Results highlight the importance of adopting an
      interpersonal perspective on finding meaning and adjustment. Limitations, future
      research and clinical implications are also discussed.

PMID- 21949007
TI  - Efficacy of tocilizumab in patients with moderate to severe active rheumatoid
      arthritis and a previous inadequate response to disease-modifying antirheumatic
      drugs: the ROSE study.
AB  - OBJECTIVE: To evaluate efficacy of tocilizumab in US patients with moderate to
      severe active rheumatoid arthritis (RA) and inadequate clinical response to
      disease-modifying antirheumatic drugs (DMARD). Safety-related outcomes were also
      analysed. METHODS: The rapid onset and systemic efficacy study was a 24-week,
      randomised, double-blind trial. Patients were randomly assigned 2:1 to
      tocilizumab 8 mg/kg (n=412) or placebo (n=207) every 4 weeks while continuing
      background DMARD in both groups. RESULTS: The primary efficacy endpoint,
      percentage of patients achieving ACR50 response at week 24, was higher with
      tocilizumab versus placebo (30.1% vs 11.2%; p<0.0001). Percentages of ACR20 and
      ACR50 responders were significantly higher with tocilizumab versus placebo as
      early as week 4 and continued to week 24; more patients in the tocilizumab versus
      placebo group also achieved ACR70 responses beginning at week 8 (p<0.01).
      Significant improvements associated with tocilizumab versus placebo were seen in
      routine assessment of patient index data responses, EULAR good response, DAS28
      and percentages of patients achieving low disease activity and clinical remission
      (based on DAS28). A substudy examining early response to therapy showed improved
      patient global assessment of disease activity (p=0.005) and pain (p=0.01) and
      DAS28 (p=0.007) with tocilizumab versus placebo at day 7. Safety findings were
      consistent with the known tocilizumab safety profile; rates of serious infections
      (per 100 patient-years) were 7.87 (95% CI 4.30 to 13.2) and 1.20 (95% CI 0.03 to
      6.66) in the tocilizumab and placebo groups, respectively. CONCLUSIONS: This
      study demonstrated the efficacy of tocilizumab in improving measures of disease
      activity in patients with RA who failed to respond adequately to DMARD therapy.
      Rapid improvement in clinical outcomes was demonstrated in a substudy as early as
      week 1 as shown by DAS28 scores, patient measures and C-reactive protein. TRIAL
      REGISTRY NO: NCT00531817.

PMID- 21949008
TI  - Comparative study of MRI and power Doppler ultrasonography of the heel in
      patients with spondyloarthritis with and without heel pain and in controls.
AB  - INTRODUCTION: Imaging of heel enthesopathy in spondyloarthritis (SpA) could
      potentially be useful for diagnosis and monitoring. The aim of this study was to
      assess the diagnostic capacities of MRI and power Doppler ultrasonography (PDUS)
      of the heel to distinguish patients with SpA from controls and to distinguish
      between patients with SpA with and without enthesopathy. METHODS: A cross
      sectional single-centre study was performed in 51 patients (102 heels) with
      definite SpA according to Amor's criteria. Patients with degenerative non
      inflammatory low back pain (n=24, 48 heels) were included as controls. Bilateral
      heel MRI and PDUS were performed by two senior musculoskeletal radiologists
      blinded to the clinical and biological data on the same day as the clinical
      evaluation. The data were analysed by patient and by heel. RESULTS: Neither MRI
      nor PDUS could discriminate between patients with SpA and controls; bone oedema
      on MRI was the only abnormality specific to SpA (94%), but with a poor
      sensitivity (22%). However, among patients with SpA, painful heels had more
      inflammatory abnormalities (81% by MRI, 58% by PDUS) than heels with no pain (56%
      at MRI, 17% at PDUS). CONCLUSION: Heel MRI and PDUS frequently show inflammatory
      lesions in SpA, particularly in painful heels. However, they were also often
      abnormal in controls. These results suggest that heel MRI and PDUS cannot be used
      for the diagnosis of SpA. However, PDUS and MRI may be useful for the depiction
      and assessment of enthesis inflammatory lesions in patients with SpA with heel
      pain.

PMID- 21949009
TI  - Light sources for single-access surgery.
AB  - BACKGROUND: Minimally invasive surgical techniques such as single access and
      natural orifice translumenal endoscopic surgery (NOTES) aim to reduce the number
      of external scars on the patient but impose restrictions on the space available
      for the light source within the endoscope and, therefore, the size of the field
      of view that can be sufficiently illuminated. MATERIALS AND METHODS: This article
      presents and compares a number of illumination methods (xenon, light-emitting
      diodes, laser/phosphor, supercontinuum laser) that could be applied in single
      access, robotic, and NOTES procedures. The luminance, spectral content, and
      intensity profile of each source was measured. Standardized images of each
      illuminating an abdominal simulator were assessed by a group of surgeons to
      provide an initial clinical impression. RESULTS: The xenon source was found to
      have the highest luminance when used with a standard laparoscopic light cable,
      but this was significantly reduced when used with a small cable suitable for
      single-access applications. The supercontinuum laser-based light source had
      brightness comparable to the xenon, which was supported by the surgical test
      group observations. CONCLUSIONS: The supercontinuum fiber probe is a potential
      alternative to xenon light sources for use in single-access surgery with its
      comparable luminance, small diameter, flexibility, and even illumination. An
      initial in vivo test is described, providing a guide for future development.

PMID- 21949010
TI  - Evaluation of a new surgical light source for difficult visibility procedures.
AB  - A new lighting device for open surgery of difficult access wounds was designed:
      the Extender add-on. The performance of the Extender is evaluated and compared
      with the conventional solutions used in the operating room (OR) on illumination
      quality. A cylindrical setup was built to measure the distribution of light in a
      simulated pelvic wound. The light was provided by a head-mounted light, an OR
      light, and a pair of Extender prototypes. The results showed that the Extender
      prototypes provided 12.2 lumens inside the wound, whereas the head-mounted light
      gave 5.7 lumens. The Extenders provided smoothly angular distributed light from 0
      degrees  to 180 degrees , whereas the head-mounted light and OR light only
      provided light from 115 degrees  to 180 degrees . The Extender prototypes had a
      promising performance in terms of light distribution. It is expected that a more
      accurately produced Extender will increase performance in terms of illumination
      quantity and illumination distribution smoothness even further.

PMID- 21949011
TI  - New technologies and surgical innovation: five years of a local health technology
      assessment program in a surgical department.
AB  - There is pressure for surgical departments to introduce new and innovative health
      technologies in an evidence-based manner while ensuring that they are safe and
      effective and can be managed with available resources. A local health technology
      assessment (HTA) program was developed to systematically integrate research
      evidence with local operational management information and to make
      recommendations for subsequent decision by the departmental executive committee
      about whether and under what conditions the technology will be used. The authors
      present a retrospective analysis of the outcomes of this program as used by the
      Department of Surgery & Surgical Services in the Calgary Health Region over a 5
      year period from December 2005 to December 2010. Of the 68 technologies
      requested, 15 applications were incomplete and dropped, 12 were approved, 3 were
      approved for a single case on an urgent/emergent basis, 21 were approved for
      "clinical audit" for a restricted number of cases with outcomes review, 14 were
      approved for research use only, and 3 were referred to additional review bodies.
      Subsequent outcome reports resulted in at least 5 technologies being dropped for
      failure to perform. Decisions based on local HTA program recommendations were
      rarely "yes" or "no." Rather, many technologies were given restricted approval
      with full approval contingent on satisfying certain conditions such as clinical
      outcomes review, training protocol development, or funding. Thus, innovation
      could be supported while ensuring safety and effectiveness. This local HTA
      program can be adapted to a variety of settings and can help bridge the gap
      between evidence and practice.

PMID- 21949012
TI  - Workplace health improvement: perspectives of environmental health officers.
AB  - BACKGROUND: Environmental health practice in the field of occupational health and
      safety is traditionally concerned with protecting health relating to the
      workplace. However, little is currently known about environmental health
      officers' (EHOs) perceptions of their role in workplace health improvement, a
      pertinent topic in light of the recent government agenda for improving the health
      of the workforce in the UK. AIMS: To explore how EHOs perceive workplace health
      improvement and its relevance to their professional role. METHODS: A qualitative
      methodology was employed, using a case-study design with thematic analysis of 15
      transcripts of in-depth telephone interviews with EHOs working in London, UK.
      RESULTS: EHOs view themselves primarily as enforcement officers, with legislation
      guiding their understandings of workplace health. Many interpret work-related ill
      health in terms of safety and physical injury and do not feel competent in
      assessing broader psychosocial elements of ill health. However, a few EHOs
      welcomed the opportunity to promote health in the workplace, recognizing the
      importance of prevention. CONCLUSIONS: This study indicates a gap between the
      contemporary EHO role framed by professional bodies as holistic and contributing
      to public health goals and the role perceived by EHOs 'on the ground'. A more
      traditional, protective and enforcement-based approach persists among EHOs in
      this sample, and few feel they have skills to address determinants beyond
      physical hazards to health. Yet, a minority of EHOs adopted a more health
      promoting approach, suggesting that the potential contribution of EHOs to the
      workplace health improvement agenda should be explored further.

PMID- 21949013
TI  - Intraspecific variation of physiological and molecular response to cadmium stress
      in Populus nigra L.
AB  - Little is known about the variability of response to heavy metal stress within
      tree species, although it could be a key for a better understanding of tolerance
      mechanisms and for breeding. The aim of the present study was to characterize the
      natural variation of response to cadmium (Cd) in Populus nigra L. in order to
      understand the mechanisms of Cd tolerance. For that, two P. nigra genotypes,
      originating from contrasting environments in northern (genotype 58-861) and
      southern (genotype Poli) Italy, were exposed to Cd stress in hydroponics for 3
      weeks. The effect of stress was estimated by measuring biomass production,
      photosynthetic performance and accumulation and translocation of Cd at the end of
      the experiment. To better understand the mechanisms of Cd tolerance, the
      expression of some candidate genes involved in the ascorbate-glutathione cycle
      (ascorbate peroxidase, glutathione reductase, glutathione S-transferase) and in
      metal sequestration (metallothioneins) was analyzed in leaves. Biomass production
      and photosynthesis were affected by the treatment in both clones but the southern
      clone was markedly more tolerant to Cd stress than the other. Nevertheless, the
      Cd content in leaves was not significantly different between the two clones and
      was quite low compared to other species. The content of thiols and phytochelatins
      (PCs), associated with the transcription profile of the glutathione S-transferase
      gene, indicated relevant differences in the use of the PCs pathway under Cd
      stress, which could explain the different tolerance to Cd. The northern clone
      accumulated thiols but down-regulated the GST gene, whereas the southern clone
      accumulated PCs and up-regulated the GST gene, which can be useful to complex and
      detoxify Cd. These results suggest that the glutathione pathway is involved in
      the differential Cd tolerance of the two genotypes. The natural germplasm of P.
      nigra represents a valuable resource for understanding tolerance to Cd and for
      selection of plant material for phytoremediation.

PMID- 21949014
TI  - Unintentional injuries among children in resource poor settings: where do the
      fingers point?
AB  - Every year, over 875,000 children between 0 and 18 years of age die as a result
      of unintentional injuries (UIs), with a higher proportion occurring in low- and
      middle-income countries (LMICs): the WHO 2008 World Report on Child Injury
      Prevention shows a child UI death rate 3.4 times greater in LMICs than in high
      income countries (HICs) (41.7 per million vs 12.2 per million, respectively).
      Deaths due to injuries from drowning, burns and falls are significantly higher
      among LMICs at 7.8, 4.3 and 2.1 per million, respectively, as compared to HICs
      with 1.2, 0.4 and 0.4 per million, respectively. The authors present a review of
      childhood UIs in LMICs undertaken to determine demographic and socioeconomic risk
      factors. As in industrialised settings, age, gender and social deprivation are
      significant factors in determining UI-related vulnerability among children.
      However, certain patterns are unique to LMICs, including road traffic injuries
      among child pedestrians, drowning and accidental paraffin poisoning. These demand
      contextual understanding and the implementation of appropriate injury control
      measures, which are currently inadequate.

PMID- 21949015
TI  - Paediatric screening for hypercholesterolaemia in Europe.
AB  - Different screening strategies are currently recommended to identify children
      with (familial) hypercholesterolaemia in order to initiate early lipid
      management. However, these strategies are characterised to date by low adherence
      by the medical community and limited compliance by parents and children. In a
      literature review, the authors assess which children should undergo screening and
      which children are in effect identified through the currently recommended
      strategies. Furthermore, the authors discuss the different screening tools and
      strategies currently used in Europe and what is known about the negative aspects
      of screening. The authors conclude that currently recommended selective screening
      strategies, which are mainly based on family history, lack precision and that a
      large percentage of affected children who are at increased risk of future
      coronary artery disease are not being identified. The authors propose universal
      screening of children between 1 and 9 years of age, a strategy likely to be most
      effective in terms of sensitivity and specificity for the identification of
      children with familial hypercholesterolaemia. However, this concept has yet to be
      proven in clinical practice.

PMID- 21949016
TI  - Cutting edge: regulatory T cells do not mediate suppression via programmed cell
      death pathways.
AB  - Regulatory T cells (Tregs) play a critical role in the immune system to regulate
      peripheral tolerance and prevent autoimmunity. However, the relative importance
      of different mechanisms of Treg function remains obscure. In this article, we
      reveal a limited role for programmed cell death pathways in mediating Treg
      suppression of conventional T cells. We show that Tregs are able to suppress the
      proliferation of conventional T cells that are resistant to apoptosis (Bim(-/-),
      Bim(-/-)Puma(-/-), Bcl-2 transgenic) or receptor-interacting serine-threonine
      kinase-dependent necrosis (also referred to as regulated necrosis or necroptosis)
      (Ripk3(-/-)) in several in vitro and in vivo assays. These data suggest that
      programmed cell death pathways, such as apoptosis and receptor-interacting serine
      threonine kinase-dependent necrosis, are not required for Treg-mediated
      suppression.

PMID- 21949017
TI  - Cutting edge: CD40-CD40 ligand pathway plays a critical CD8-intrinsic and 
      extrinsic role during rescue of exhausted CD8 T cells.
AB  - CD8 exhaustion mediated by an inhibitory programmed death-1-programmed death
      ligand-1 (PD-L1) pathway occurs in several chronic infections, including
      toxoplasmosis. Although blockade of the programmed death-1-PD-L1 pathway revives
      this response, the role of costimulatory receptors involved in this rescue has
      not been ascertained in any model of CD8 exhaustion. This report demonstrates
      that one such costimulatory pathway, CD40-CD40L, plays a critical role during
      rescue of exhausted CD8 T cells. Blockade of this pathway abrogates the
      ameliorative effects of anti-PD-L1 treatment on CD8 T cells. Additionally, we
      demonstrate in an infectious disease model that CD8-intrinsic CD40 signaling is
      important for optimal CD8 polyfunctionality, proliferation, T-bet upregulation,
      and IL-21 signaling, albeit in the context of CD8 rescue. The critical role of
      CD40 during the rescue of exhausted CD8 T cells may provide a rational basis for
      designing novel therapeutic vaccination approaches.

PMID- 21949018
TI  - Cutting edge: IRF8 regulates Bax transcription in vivo in primary myeloid cells.
AB  - A prominent phenotype of IRF8 knockout (KO) mice is the uncontrolled expansion of
      immature myeloid cells. The molecular mechanism underlying this
      myeloproliferative syndrome is still elusive. In this study, we observed that Bax
      expression level is low in bone marrow preginitor cells and increases
      dramatically in primary myeloid cells in wt mice. In contrast, Bax expression
      level remained at a low level in primarymyeloid cells in IRF8 KO mice. However,
      in vitro IRF8 KO bone marrow-differentiated myeloid cells expressed Bax at a
      level as high as that in wild type myeloid cells. Furthermore, we demonstrated
      that IRF8 specifically binds to the Bax promoter region in primary myeloid cells.
      Functional analysis indicated that IRF8 deficiency results in increased
      resistance of the primary myeloid cells to Fas-mediated apoptosis. Our findings
      show that IRF8 directly regulates Bax transcription in vivo, but not in vitro
      during myeloid cell lineage differentiation.

PMID- 21949019
TI  - Role of IL-17A in neutrophil recruitment and hepatic injury after warm ischemia
      reperfusion mice.
AB  - Recent evidence suggests that IL-17A regulates neutrophil-dependent organ injury.
      Accordingly, the purpose of this study was to determine the role of IL-17A in
      neutrophil recruitment after ischemia-reperfusion (I/R) and in subsequent liver
      injury. Two mouse models including wild-type and IL-17A knockout mice were
      evaluated for I/R injury. The medial largest lobe of the liver was clamped for 90
      min. In another set of experiments, recombinant mouse (rm)IL-17A homodimer or
      rmIL-17A/F heterodimer were administered to knockout mice before I/R, and liver
      injury was investigated. Isolated Kupffer cells were incubated with rmIL-17A or
      rmIL-17F, and production of TNF-alpha was measured. Studies evaluating the extent
      of liver injury as measured by serum transaminase levels demonstrated similar
      levels in the acute phase (6 h) in these two models. In contrast, in the subacute
      phase (20 h) after I/R, both serum transaminase levels and percent of hepatic
      necrosis were significantly reduced in the knockout mice compared with the wild
      type mice. This reduction in liver injury seen in the knockout mice was
      associated with suppression of chemokine and adhesion molecule expression and
      reduction in infiltration of neutrophils into the liver. Administration of rmIL
      17A homodimer, but not IL-17A/F heterodimer, increased liver injury in the
      subacute phase of I/R in KO mice. TNF-alpha production by isolated Kupffer cells
      increased significantly in the cells incubated with rmIL-17A compared with rmIL
      17F. These results indicate that IL-17A is a key regulator in initiating
      neutrophil-induced inflammatory responses and hepatic injury in the subacute
      phase after reperfusion.

PMID- 21949020
TI  - The SLP-76 Src homology 2 domain is required for T cell development and
      activation.
AB  - The adapter protein Src homology 2 (SH2) domain-containing leukocyte protein of
      76 kDa (SLP-76) is critical for multiple aspects of T cell development and
      function. Through its protein-binding domains, SLP-76 serves as a platform for
      the assembly of multiple enzymes and adapter proteins that function together to
      activate second messengers required for TCR signal propagation. The N terminus of
      SLP-76, which contains three tyrosines that serve as docking sites for SH2 domain
      containing proteins, and the central proline-rich region of SLP-76 have been well
      studied and are known to be important for both thymocyte selection and activation
      of peripheral T cells. Less is known about the function of the C-terminal SH2
      domain of SLP-76. This region inducibly associates with ADAP and HPK1. Combining
      regulated deletion of endogenous SLP-76 with transgenic expression of a SLP-76
      SH2 domain mutant, we demonstrate that the SLP-76 SH2 domain is required for
      peripheral T cell activation and positive selection of thymocytes, a function not
      previously attributed to this region. This domain is also important for T cell
      proliferation, IL-2 production, and phosphorylation of protein kinase D and
      IkappaB. ADAP-deficient T cells display similar, but in some cases less severe,
      defects despite phosphorylation of a negative regulatory site on SLP-76 by HPK1,
      a function that is lost in SLP-76 SH2 domain mutant T cells.

PMID- 21949021
TI  - Sensitivity and resistance to regulation by IL-4 during Th17 maturation.
AB  - Th17 cells are highly pathogenic in a variety of immune-mediated diseases, and a
      thorough understanding of the mechanisms of cytokine-mediated suppression of Th17
      cells has great therapeutic potential. In this article, we characterize the
      regulation of both in vitro- and in vivo-derived Th17 cells by IL-4. We
      demonstrate that IL-4 suppresses reactivation of committed Th17 cells, even in
      the presence of TGF-beta, IL-6, and IL-23. Downregulation of IL-17 by IL-4 is
      dependent on STAT6 and mediated by inhibition of STAT3 binding at the Il17a
      promoter. Although Th1 cytokines were shown to induce IFN-gamma expression by
      Th17 cells, IL-4 does not induce a Th2 phenotype in Th17 cells. Suppression by IL
      4 is stable and long-lived when applied to immature Th17 cells, but cells that
      have undergone multiple rounds of stimulation, either in vivo during a Th17
      mediated inflammatory disease, or in vitro, become resistant to suppression by IL
      4 and lose the ability to signal through IL-4R. Thus, although IL-4 is a potent
      suppressor of the Th17 genetic program at early stages after differentiation,
      prolonged stimulation renders Th17 cells impervious to regulatory cytokines.

PMID- 21949022
TI  - Enhancement of antibody class-switch recombination by the cumulative activity of
      four separate elements.
AB  - Class-switch recombination of Ab isotype is mediated by a recombinational DNA
      deletion event and must be robustly upregulated during Ag-driven differentiation
      of B cells. The enhancer region 3' of the Calpha gene is important for the
      upregulation of switch recombination. Using a transgene of the entire H chain C
      region locus, we demonstrate in this study that it is the four 3' enhancer
      elements themselves (a total of 4.7 kb) that are responsible for the upregulation
      rather than the 24 kb of DNA in between them. Neither allelic exclusion nor
      transgenic MU expression is reduced by deletion of the four 3' enhancers. We also
      test deletions of two or three of the 3' enhancers and show that deletion of more
      3' enhancers results in a progressive reduction in both switch recombination and
      germline transcription of all H chain genes. Nevertheless, we find evidence for
      special roles for some 3' enhancers; different H chain genes are affected by
      different 3' enhancer deletions. Thus, we find that the dramatic induction of
      class-switch recombination during Ag-driven differentiation is the result of an
      interaction among four separated regulatory elements.

PMID- 21949023
TI  - The link between the PDL1 costimulatory pathway and Th17 in fetomaternal
      tolerance.
AB  - Fetomaternal tolerance has been shown to depend both on regulatory T cells
      (Tregs) and negative signals from the PD1-PDL1 costimulatory pathway. More
      recently, IL-17-producing T cells (Th17) have been recognized as a barrier in
      inducing tolerance in transplantation. In this study, we investigate the
      mechanisms of PDL1-mediated regulation of fetomaternal tolerance using an
      alloantigen-specific CD4(+) TCR transgenic mouse model system (ABM-tg mouse).
      PDL1 blockade led to an increase in embryo resorption and a reduction in litter
      size. This was associated with a decrease in Tregs, leading to a lower
      Treg/effector T cell ratio. Moreover, PDL1 blockade inhibited Ag-specific
      alloreactive T cell apoptosis and induced apoptosis of Tregs and a shift toward
      higher frequency of Th17 cells, breaking fetomaternal tolerance. These Th17 cells
      arose predominantly from CD4(+)Foxp3(-) cells, rather than from conversion of
      Tregs. Locally in the placenta, similar decrease in regulatory and apoptotic
      markers was observed by real-time PCR. Neutralization of IL-17 abrogated the anti
      PDL1 effect on fetal survival rate and restored Treg numbers. Finally, the
      adoptive transfer of Tregs was also able to improve fetal survival in the setting
      of PDL1 blockade. This is to our knowledge the first report using an alloantigen
      specific model that establishes a link between PDL1, Th17 cells, and fetomaternal
      tolerance.

PMID- 21949024
TI  - Blockade of Notch ligand delta1 promotes allograft survival by inhibiting
      alloreactive Th1 cells and cytotoxic T cell generation.
AB  - The Notch signaling pathway has been recently shown to contribute to T cell
      differentiation in vitro. However, the in vivo function of Notch signaling in
      transplantation remains unknown. In this study, we investigated the importance of
      Delta1 in regulating the alloimmune response in vivo. Delta1 expression was
      upregulated on dendritic cells and monocytes/macrophages upon transplantation in
      a BALB/c into B6 vascularized cardiac transplant model. Whereas administration of
      anti-Delta1 mAb only slightly delayed survival of cardiac allografts in this
      fully MHC-mismatched model, it significantly prolonged graft survival in
      combination with single-dose CTLA4-Ig or in CD28 knockout recipients. The
      prolongation of allograft survival was associated with Th2 polarization and a
      decrease in Th1 and granzyme B-producing cytotoxic T cells. The survival benefit
      of Delta1 blockade was abrogated after IL-4 neutralization and in STAT6KO
      recipients, but was maintained in STAT4KO recipients, reinforcing the key role of
      Th2 cell development in its graft-prolonging effects. To our knowledge, these
      data demonstrate for the first time an important role of Delta1 in alloimmunity,
      identifying Delta1 ligand as a potential novel target for immunomodulation in
      transplantation.

PMID- 21949026
TI  - MHC-independent genetic factors control the magnitude of CD4+ T cell responses to
      amyloid-beta peptide in mice through regulatory T cell-mediated inhibition.
AB  - Accumulation of amyloid-beta peptide (Abeta) is considered the triggering factor
      of pathogenic lesions in Alzheimer's disease (AD), and vaccines targeting Abeta
      are promising therapeutic options. However, the occurrence of
      meningoencephalitides attributed to T cell responses in 6% of Abeta-immunized
      patients underscores the need for a better understanding of T cell responses to
      Abeta. We characterized the parameters controlling the magnitude of Abeta
      specific CD4(+) T cell responses in mice. T cell responsiveness to Abeta1-42 was
      highly heterogeneous between mouse strains of different H-2 haplotypes, with
      SJL/J (H-2(s)) mice displaying a strong response, mainly specific for Abeta10-24,
      and C57BL/6 (H-2(b)) mice displaying a weak response to Abeta16-30. Surprisingly,
      C57BL/6 mice congenic for the H-2(s) haplotype (B6.H-2(S)), which display a
      "permissive" MHC class II allele for presentation of the immunodominant Abeta10
      24 epitope, showed a very weak CD4(+) T cell response to Abeta, suggesting that
      MHC-independent genes downmodulate Abeta-specific CD4(+) T cell responses in
      C57BL/6 background. Vaccine-induced CD4(+) T cell responses to Abeta were
      significantly enhanced in both C57BL/6 and B6.H-2(S) mice upon depletion of
      regulatory T cells (Tregs), whereas Treg-depleted SJL/J mice displayed unaltered
      Abeta-specific T cell responses. Finally, Treg depletion in C57BL/6 transgenic
      APPPS1 mice, a mouse model of AD, results in enhanced vaccine-induced CD4(+) T
      cell responses in AD compared with wild-type animals. We concluded that the
      magnitude of Abeta-specific CD4(+) T cell responses is critically controlled in
      both physiological and pathological settings by MHC-independent genetic factors
      that determine the overall potency of Abeta-specific Treg responses.

PMID- 21949025
TI  - IL-33 expands suppressive CD11b+ Gr-1(int) and regulatory T cells, including
      ST2L+ Foxp3+ cells, and mediates regulatory T cell-dependent promotion of cardiac
      allograft survival.
AB  - IL-33 administration is associated with facilitation of Th2 responses and
      cardioprotective properties in rodent models. However, in heart transplantation,
      the mechanism by which IL-33, signaling through ST2L (the membrane-bound form of
      ST2), promotes transplant survival is unclear. We report that IL-33
      administration, while facilitating Th2 responses, also increases immunoregulatory
      myeloid cells and CD4(+) Foxp3(+) regulatory T cells (Tregs) in mice. IL-33
      expands functional myeloid-derived suppressor cells, CD11b(+) cells that exhibit
      intermediate (int) levels of Gr-1 and potent T cell suppressive function.
      Furthermore, IL-33 administration causes an St2-dependent expansion of
      suppressive CD4(+) Foxp3(+) Tregs, including an ST2L(+) population. IL-33
      monotherapy after fully allogeneic mouse heart transplantation resulted in
      significant graft prolongation associated with increased Th2-type responses and
      decreased systemic CD8(+) IFN-gamma(+) cells. Also, despite reducing overall
      CD3(+) cell infiltration of the graft, IL-33 administration markedly increased
      intragraft Foxp3(+) cells. Whereas control graft recipients displayed increases
      in systemic CD11b(+) Gr-1(hi) cells, IL-33-treated recipients exhibited increased
      CD11b(+) Gr-1(int) cells. Enhanced ST2 expression was observed in the myocardium
      and endothelium of rejecting allografts, however the therapeutic effect of IL-33
      required recipient St2 expression and was dependent on Tregs. These findings
      reveal a new immunoregulatory property of IL-33. Specifically, in addition to
      supporting Th2 responses, IL-33 facilitates regulatory cells, particularly
      functional CD4(+) Foxp3(+) Tregs that underlie IL-33-mediated cardiac allograft
      survival.

PMID- 21949027
TI  - Stomatal (mis)behaviour.
AB  - When stomata first evolved they initiated the greening of terrestrial earth, and
      now more than 400 million years later these simple bi-cellular valves in the leaf
      surface regulate global fluxes of water and carbon. Despite their importance and
      superficial simplicity, the behaviour of stomata remains a great challenge to
      understand. Different approaches to studying stomatal control have yielded rather
      disparate models for how stomata respond to environmental stimuli. Much of this
      discord arises from the diversity of mechanisms apparently involved in changing
      guard cell turgor and hence the aperture of the stomatal pore. On the one hand,
      the physical tension produced by dragging water from the soil through the xylem
      to the leaves directly influences leaf and guard cell turgor, while on the other
      hand, phytohormone levels (most importantly abscisic acid), light, photosynthesis
      and atmospheric gases induce active changes in guard cell turgor by triggering
      ionic pumping. Each stomatal control mechanism has its own champion and no model
      has ever successfully integrated all components. In such an environment there is
      great value in examining how different parts of the stomatal control network
      interact, particularly the competition between 'hydraulic' signals related to
      leaf water content and 'metabolic' signals related to ambient photosynthetic
      conditions.

PMID- 21949028
TI  - Determination of structural regions important for Ca(2+) uptake activity in
      Arabidopsis MCA1 and MCA2 expressed in yeast.
AB  - MCA1 is a plasma membrane protein that correlates Ca(2+) influx and
      mechanosensing in Arabidopsis. MCA2 is a paralog of MCA1, and both share 72.7%
      amino acid sequence identity and several common structural features, including
      putative transmembrane (TM) segments, an EF hand-like region in the N-terminal
      half, a coiled-coil motif in the middle and a PLAC8 motif in the C-terminal half.
      To determine structural regions important for Ca(2+) uptake activity, the
      activity of truncated forms of MCA1 and MCA2 was assessed using yeast expression
      assays. The N-terminal half of MCA1 with a coiled-coil motif (MCA1(1-237)) did
      not have Ca(2+) uptake activity, while MCA2(1-237) did. The N-terminal half of
      MCA1 without the coiled-coil motif (MCA1 (1-185)) showed Ca(2+) uptake activity,
      as did MCA2(1-186). Both MCA1(1-173) and MCA2(1-173) having the EF hand-like
      region had Ca(2+) uptake activity. Deletion of a putative TM segment (Ile11
      Ala33) and the Asp21 to asparagine mutation in MCA1 and MCA2 abolished Ca(2+)
      uptake activity. Finally, MCA1(173-421) and MCA2(173-416) lacking the N-terminal
      half had no Ca(2+) uptake activity. These results suggest that the N-terminal
      half of both proteins with the EF hand-like region is necessary and sufficient
      for Ca(2+) uptake and that the coiled-coil motif regulates MCA1 negatively and
      MCA2 positively.

PMID- 21949029
TI  - Actin-dependent chloroplast anchoring is regulated by Ca(2+)-calmodulin in
      spinach mesophyll cells.
AB  - Chloroplasts are actively anchored at the appropriate intracellular regions to
      maintain advantageous distribution patterns under specific environmental
      conditions. Redistribution of chloroplasts is accompanied by their de-anchoring
      and re-anchoring, respectively, from and to the cortical cytoplasm. In spinach
      mesophyll cells, high-intensity blue light and Ca(2+) treatment induced the
      disappearance of the meshwork-like array of actin filaments surrounding
      chloroplasts, which was suppressed by a calmodulin antagonist. Regulatory
      mechanisms of chloroplast anchoring were investigated using plasma membrane (PM)
      ghosts, on which the cortical cytoplasm underlying the PM was exposed. Addition
      of an actin-depolymerizing reagent or > 1 uM Ca(2+) induced detachment of a
      substantial number of chloroplasts from the PM ghosts concomitant with disordered
      actin organization. Calmodulin antagonists and anti-calmodulin antibodies negated
      the effects of Ca(2+). In addition, Ca(2+)-induced detachment of chloroplasts was
      no longer evident on the calmodulin-depleted PM ghosts. We propose that
      chloroplasts are anchored onto the cortical cytoplasm through interaction with
      the actin cytoskeleton, and that Ca(2+)-calmodulin-sensitized de-anchoring of
      chloroplasts is a critical early step in chloroplast redistribution induced by
      environmental stimuli.

PMID- 21949030
TI  - Functional evaluation of a nitrogenase-like protochlorophyllide reductase encoded
      by the chloroplast DNA of Physcomitrella patens in the cyanobacterium
      Leptolyngbya boryana.
AB  - Dark-operative protochlorophyllide (Pchlide) oxidoreductase (DPOR) is a
      nitrogenase-like enzyme consisting of the two components, L-protein (a ChlL
      dimer) and NB-protein (a ChlN-ChlB heterotetramer), to catalyze Pchlide reduction
      in Chl biosynthesis. While nitrogenase is distributed only among certain
      prokaryotes, the probable structural genes for DPOR are encoded by chloroplast
      DNA in lower plants. Here we show functional evaluation of DPOR encoded by
      chloroplast DNA in a moss Physcomitrella patens by the complementation analysis
      of the cyanobacterium Leptolyngbya boryana and the heterologous reconstitution of
      the moss L-protein and the cyanobacterial NB-protein. Two shuttle vectors to
      overexpress chlL and chlN-chlB from P. patens were introduced into the
      cyanobacterial chlL- and chlB-lacking mutants, respectively. Both transformants
      restored the ability to perform Chl biosynthesis in the dark, indicating that the
      chloroplast-encoded DPOR components form an active complex with the
      cyanobacterial components. The L-protein of P. patens was purified from the
      cyanobacterial transformant, and DPOR activity was reconstituted in a
      heterologous combination with the cyanobacterial NB-protein. The specific
      activity of the L-protein from P. patens was determined to be 118 nmol min(-1) mg
      (-1), which is even higher than that of the cyanobacterial L-protein (76 nmol
      min(-1) mg (-1)). Upon exposure to air, the activity of the L-protein from P.
      patens decayed with a half-life of 30 s, which was eight times faster than that
      of the cyanobacterial L-protein (240 s). These results suggested that the
      chloroplast-encoded L-protein functions as efficiently as the cyanobacterial L
      protein but is more oxygen labile than the cyanobacterial L-protein.

PMID- 21949031
TI  - Preventing pressure ulcers in long-term care: a cost-effectiveness analysis.
AB  - BACKGROUND: Pressure ulcers are common in many care settings, with adverse health
      outcomes and high treatment costs. We evaluated the cost-effectiveness of
      evidence-based strategies to improve current prevention practice in long-term
      care facilities. METHODS: We used a validated Markov model to compare current
      prevention practice with the following 4 quality improvement strategies: (1)
      pressure redistribution mattresses for all residents, (2) oral nutritional
      supplements for high-risk residents with recent weight loss, (3) skin emollients
      for high-risk residents with dry skin, and (4) foam cleansing for high-risk
      residents requiring incontinence care. Primary outcomes included lifetime risk of
      stage 2 to 4 pressure ulcers, quality-adjusted life-years (QALYs), and lifetime
      costs, calculated according to a single health care payer's perspective and
      expressed in 2009 Canadian dollars (Can$1 = US$0.84). RESULTS: Strategies cost on
      average $11.66 per resident per week. They reduced lifetime risk; the associated
      number needed to treat was 45 (strategy 1), 63 (strategy 4), 158 (strategy 3),
      and 333 (strategy 2). Strategy 1 and 4 minimally improved QALYs and reduced the
      mean lifetime cost by $115 and $179 per resident, respectively. The cost per QALY
      gained was approximately $78 000 for strategy 3 and $7.8 million for strategy 2.
      If decision makers are willing to pay up to $50 000 for 1 QALY gained, the
      probability that improving prevention is cost-effective is 94% (strategy 4), 82%
      (strategy 1), 43% (strategy 3), and 1% (strategy 2). CONCLUSIONS: The clinical
      and economic evidence supports pressure redistribution mattresses for all long
      term care residents. Improving prevention with perineal foam cleansers and dry
      skin emollients appears to be cost-effective, but firm conclusions are limited by
      the available clinical evidence.

PMID- 21949032
TI  - Health outcome prioritization as a tool for decision making among older persons
      with multiple chronic conditions.

PMID- 21949033
TI  - Hip fracture and increased short-term but not long-term mortality in healthy
      older women.
AB  - BACKGROUND: Fractures have been associated with subsequent increases in
      mortality, but it is unknown how long that increase persists. METHODS: A total of
      5580 women from a large community-based, multicenter US prospective cohort of
      9704 (Study of Osteoporotic Fractures) were observed prospectively for almost 20
      years. We age-matched 1116 hip fracture cases with 4 control participants (n =
      4464). To examine the effect of health status, we examined a healthy older subset
      (n = 960) 80 years or older who attended the 10-year follow-up examination and
      reported good or excellent health. Incident hip fractures were adjudicated from
      radiology reports by study physicians. Death was confirmed by death certificates.
      RESULTS: Hip fracture cases had 2-fold increased mortality in the year after
      fracture compared with controls (16.9% vs 8.4%; multivariable adjusted odds ratio
      [OR], 2.4; 95% CI, 1.9-3.1]. When examined by age and health status, short-term
      mortality was increased in those aged 65 to 69 years (16.3% vs 3.7%; OR, 5.0; 95%
      CI, 2.6-9.5), 70 to 79 years (16.5% vs 8.9%; OR, 2.4; 95% CI, 1.8-3.3), and only
      in those 80 years or older with good or excellent health (15.1% vs 7.2%;
      multivariable adjusted OR, 2.8; 95% CI, 1.5-5.2). After the first year, survival
      of hip fracture cases and controls was similar except in those aged 65 to 69
      years, who continued to have increased mortality. CONCLUSIONS: Short-term
      mortality is increased after hip fracture in women aged 65 to 79 years and in
      exceptionally healthy women 80 years or older. Women 70 years or older return to
      previous risk levels after a year. Interventions are needed to decrease mortality
      in the year after hip fracture, when mortality risk is highest.

PMID- 21949034
TI  - Platelet activity indices in patients with deep vein thrombosis.
AB  - BACKGROUND: Extensive research has been performed regarding the association
      between platelet activity indices and various cardiovascular disorders. Less
      clear data, however, are present between these indices and deep vein thrombosis
      (DVT). AIM: The aim of this study was to investigate the association between
      platelet activity indices and DVT in a relatively large population. METHODS: Mean
      platelet volume (MPV), mean platelet mass (MPM), and mean platelet component
      (MPC) were measured by an autoanalyzer in a total of 203 patients with DVT and
      the results were compared with 210 age- and sex-matched controls without DVT.
      RESULTS: There were significant differences between the study and control groups
      in MPV (8.6 +/- 1.3 fL vs 7.9 +/- 0.5 fL [95% CI -0.82 to -0.44], P < .001,
      respectively), MPM (2.2 +/- 0.3 pg vs 2.0 +/- 0.1 pg [95% CI -0.20 to -0.11], P <
      .001, respectively), and MPC (24.9 +/- 3.2 g/dL vs 26.3 +/- 1.6 g/dL [95% CI 0.91
      to 1.89], P < .001, respectively). These 3 platelet activity indices were also
      found to be significant predictors of the presence of DVT (all Ps < .001).
      CONCLUSION: In patients with DVT, the presence of DVT was closely associated with
      increased platelet activation. The MPV, MPM, and MPC may identify patients
      requiring aggressive antiplatelet treatment.

PMID- 21949036
TI  - Generic versus branded enoxaparin in the prevention of venous thromboembolism
      following major abdominal surgery: report of an exploratory clinical trial.
AB  - INTRODUCTION: Several generic low-molecular-weight heparins (LMWHs) have recently
      become available worldwide, including the United States. Companies have filed for
      regulatory approval of generic versions in many countries, based only on compound
      biochemical characteristics or its immunogenicity. METHODS: Prospective study to
      evaluate the comparative effect of 2 enoxaparins (Sanofi-Aventis branded
      enoxaparin [SAe] vs eurofarma-enoxaparin [Ee], a generic version) as prophylaxis
      for venous thromboembolism (VTE) following major abdominal surgery. A total of
      200 patients were randomized in a 1:1 ratio either to receive 40 mg of SAe or Ee
      subcutaneously (sc) once daily (od) postoperatively for 7 to 10 days. Compressive
      ultrasound was performed on day 10 + 4. RESULTS: No statistically significant
      differences between the 2 groups were detected. In all, 2 SAe patients presented
      deep vein thrombosis ([DVT] 2.1%), none of the Ee group. No major bleeding events
      occurred. CONCLUSIONS: This exploratory trial suggests that the generic LMWH is
      probably as safe and as effective as the branded enoxaparin (Lovenox, Brazil) in
      the prophylaxis of VTE in this population.

PMID- 21949035
TI  - Significant associations among hemostatic parameters, adipokines, and components
      of the metabolic syndrome in Japanese preschool children.
AB  - Development of cardiovascular diseases could originate in early childhood.
      However, reference values of hemostatic parameters and adipokines in preschool
      children remain to be explored. We measured blood levels of adipokines and
      parameters of the hemostatic/fibrinolytic systems in 167 healthy children aged 4
      to 6 years at 9:00 to 10:30 am after a strictly enforced overnight fast.
      Participants with body mass index (BMI) values >=90th percentile had
      significantly higher values of systolic blood pressure and heart rate, as well as
      blood levels of insulin, coagulation factor (F) VII, FX, protein S, leptin, and
      homeostasis model assessment of insulin resistance (HOMA-IR), and lower values of
      desacyl-ghrelin than children with BMI < 90th percentile. Circulating levels of
      fibrinogen and leptin increased with increased number of cardiovascular risk
      factors. Stepwise regression analysis identified many hematological variables to
      be associated with features of the metabolic syndrome. The results implicated the
      hemostatic/fibrinolytic system or adipokines in the insidious progression of
      cardiovascular diseases from an early age.

PMID- 21949037
TI  - Good short-term but not long-term reproducibility of the antiplatelet efficacy
      laboratory assessment.
AB  - BACKGROUND: The antiplatelet effect of acetylsalicylic acid (ASA) varies among
      individual patients. We assessed the short-term reproducibility (STR) and long
      term reproducibility (LTR) of light transmission aggregometry (LTA). METHODS:
      Residual platelet reactivity was measured twice using LTA in a group of 207
      consecutive patients (56 females, mean age 67 +/- 9 years) on ASA therapy in 10
      +/- 6 months interval. The STR was assessed in 15 patients (6 females, mean age
      61 +/- 7 years) with 10 measurements on 2 consecutive days. RESULTS: There was no
      correlation between both measurements in the long-term part of the study, and
      also Bland-Altman plot showed a diverging pattern. However, LTA STR was good with
      a correlation coefficient of .800 (P < .05) confirmed by Bland-Altman plot.
      CONCLUSIONS: Although short-term intraindividual reproducibility of LTA
      assessment of platelet reactivity is very good, in the long-term perspective the
      antiplatelet ASA effectivity may be influenced by additional variables and
      repeated measurements are warranted.

PMID- 21949038
TI  - Biomarkers of inflammation, growth factor, and coagulation activation in patients
      with sickle cell disease.
AB  - Acute painful crisis is a common sequela that can cause significant morbidity and
      negatively impact the quality of life of patients with sickle cell disease (SCD).
      Plasma levels of several chemokines and cytokines including tumor necrosis factor
      alpha (TNF-alpha), interleukin 1beta (IL-1beta), IL-6, IL-8, monocyte
      chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1alpha (MIP
      1alpha), and interferon gamma (IFN-gamma) in patients with SCD showed a distinct
      and statistically significant rise either during painful crisis or at steady
      state. Plasma levels of various growth factors, including human vascular
      endothelial growth factor (VEGF), human basic fibroblast growth factor (FGF), and
      human hepatocyte growth factor (HGF), showed a sustained 2- to 3-fold increase
      either during painful crisis or at steady state in patients with SCD.
      Furthermore, plasma levels of the biomarker d-Dimer, a marker of
      hypercoagulation, showed a 2- to 3-fold increase either during painful crisis or
      at steady state in patients with SCD as compared to that in healthy participants,
      suggesting an increased risk of thrombosis.

PMID- 21949039
TI  - The influence of the ABO blood type on the distribution of von Willebrand factor
      in healthy children with no bleeding symptoms.
AB  - The purpose of this study was to determine the effect of ABO blood groups on von
      Willebrand factor-ristocetin cofactor activity (vWF-RCo) and on vWF-antigen (vWF
      Ag) in children who have no personal or familial history of bleeding. MATERIAL
      AND METHODS: A survey and testing were performed on 200 children with no personal
      or familial history of bleeding. In all, 100 of them belonged to blood group O,
      and the remaining 100 belonged to other blood groups. The blood samples were
      stored at -80 degrees C for a maximum period of 2 weeks to detect vWF-RCo and vWF
      Ag levels. RESULTS: The mean vWF-Ag (+/- 2 standard deviation [SD]) level in
      children with blood group O was 86% (+/- 20%); and for those with non-O blood
      group, it was 98.8% (+/- 25%). There was a significant difference between the 2
      groups (P < .001). The mean vWF-RCo (+/- 2 SD) level in children with blood group
      O was 89% (+/- 23%); and for those with non-O blood group, it was 103% (+/- 17%).
      There was a significant difference between those in the 2 groups (P < .001). The
      lowest value of vWF-Ag and vWF-RCo levels in children with blood group O was
      found to be 50%. In conclusion, we showed that the selection of normal ranges
      based on the ABO group might influence the clinical diagnosis of vWD and that
      while the approach of using ABO group ranges for a vWF-Ag level lower than 50
      IU/dL is scientifically sound, it might not be useful to assist a clinician in
      identifying people at increased risk of bleeding.

PMID- 21949040
TI  - Diagnosis and management of isolated subsegmental pulmonary embolism: review and
      assessment of the options.
AB  - We assessed the potential safety of withholding treatment of pulmonary embolism
      (PE) limited to subsegmental branches. Literature review showed that untreated
      patients with mostly subsegmental PE had no fatal recurrences in 1 to 3 months
      and no nonfatal recurrences of PE in 3 months. Patients with suspected PE who had
      nondiagnostic ventilation/perfusion lung scans, adequate cardiorespiratory
      reserve or low or moderate clinical probability, and negative serial noninvasive
      leg tests were shown not to require treatment. It appears safe, therefore, to
      withhold treatment of subsegmental PE providing (1) pulmonary-respiratory reserve
      is good; (2) no evidence of deep venous thrombosis (DVT) on serial testing; (3)
      major risk factor for PE was transient and no longer present; (4) no history of
      central venous catheterization or atrial fibrillation; and (5) willingness to
      return for serial venous ultrasound. After fully informing patients, some may
      choose to be treated and some may choose not to be treated.

PMID- 21949041
TI  - Venous thromboembolism pharmacy intervention management program with an active,
      multifaceted approach reduces preventable venous thromboembolism and increases
      appropriate prophylaxis.
AB  - Two concepts relating to venous thromboembolism (VTE) prevention have recently
      emerged-"appropriate" prophylaxis and "preventable" VTE. We evaluated whether a
      human alert, as part of a pharmacy intervention program, can increase appropriate
      prophylaxis and decrease preventable symptomatic VTE in hospitalized patients.
      This prospective study with retrospective data collection was conducted utilizing
      data from 1879 patients in 2006 as a control cohort. The intervention cohort data
      were from 1646 patients during 2007, after program implementation. The rate of
      appropriate prophylaxis increased from 23.8% in 2006 to 37.9% in 2007 (odds ratio
      1.8; 95% confidence interval [CI] = 1.6-2.1; P < .0001). Preventable VTE
      incidence was reduced by 74% (95% CI = 44%-88%) from 18.6 to 4.9 per 1000 patient
      discharges in 2006 and 2007, respectively (P = .0006). In conclusion, a pharmacy
      led multifaceted intervention can significantly increase the rates of appropriate
      prophylaxis and significantly reduce the incidence of preventable VTE in
      hospitalized patients.

PMID- 21949042
TI  - Safety and immunogenicity of live attenuated and inactivated influenza vaccines
      in children with cancer.
AB  - BACKGROUND: The safety and immunogenicity of live, attenuated influenza vaccine
      (LAIV) has not been compared to that of the standard trivalent inactivated
      vaccine (TIV) in children with cancer. METHODS: Randomized study of LAIV versus
      TIV in children with cancer, age 2-21 years, vaccinated according to
      recommendations based on age and prior vaccination. Data on reactogenicity and
      other adverse events and blood and nasal swab samples were obtained following
      vaccination. RESULTS: Fifty-five eligible subjects (mean age, 10.4 years)
      received vaccine (28 LAIV/27 TIV). Both vaccines were well tolerated. Rhinorrhea
      reported within 10 days of vaccination was similar in both groups (36% LAIV vs
      33% TIV, P > .999). Ten LAIV recipients shed virus; the latest viral shedding was
      detected 7 days after vaccination. Immunogenicity data were available for 52
      subjects, or 26 in each group. TIV induced significantly higher postvaccination
      geometric mean titers against influenza A viruses (P < .001), greater
      seroprotection against influenza A/H1N1 (P = .01), and greater seroconversion
      against A/H3N2 (P = .004), compared with LAIV. No differences after vaccination
      were observed against influenza B viruses. CONCLUSIONS: As expected, serum
      antibody response against influenza A strains were greater with TIV than with
      LAIV in children with cancer. Both vaccines were well tolerated, and prolonged
      viral shedding after LAIV was not detected. CLINICAL TRIALS REGISTRATION:
      NCT00906750.

PMID- 21949043
TI  - Adoptive transfer of dendritic cells pulsed with Fasciola hepatica antigens and
      lipopolysaccharides confers protection against fasciolosis in mice.
AB  - Dendritic cells (DCs) can function as adjuvants able to mediate protection
      against different pathogens. Given that successful vaccination against Fasciola
      hepatica is mostly related to the induction of Th1 responses, we studied the
      potential of DCs loaded with F. hepatica antigens and lipopolysaccharide (LPS)
      (which promote DCs maturation) as a vaccine against fasciolosis in BALB/c mice.
      However, only a semimature phenotype was achieved when DCs were simultaneously
      cultured with an F. hepatica total extract (TE) and LPS. The activation status of
      TE-loaded DCs was enhanced when these cells were treated with TE 90 minutes
      before being stimulated with LPS (TE90 DCs). More importantly, a single
      vaccination of mice with TE90 DCs stimulated a systemic Th1 response and
      conferred protection against hepatic damage induced by F. hepatica infection.
      Thus, TE90 DCs may prove to be a useful new tool for vaccination against F.
      hepatica.

PMID- 21949044
TI  - Make new friends, but keep the old: influenza vaccines in children with cancer.

PMID- 21949045
TI  - Parenteral peramivir treatment for Oseltamivir-resistant 2009 pandemic influenza
      A H1N1 viruses.

PMID- 21949046
TI  - Why clinical psychology needs process research: an examination of four
      methodologies.
AB  - This paper advocates for process research as a valid source of evidence in
      clinical psychology, research that focuses on why and how therapy works, both
      across the course of treatment and in the minutiae of interactions between
      therapist and client. Process research is consistent with the aims of the
      scientist-practitioner model, supporting the provision of practical and realistic
      guidance to clinicians. Specific examples of methods are provided, including the
      analysis of mechanisms of change, patient-focused research, conversational
      analysis and interpersonal process recall.

PMID- 21949047
TI  - Applying child specific knowledge in reflective dialogues: presentation of an
      approach.
AB  - The vantage point of this article is the growing body of knowledge about how the
      child's interaction with its caregivers impacts on later development. With
      reference to the Transaction Model it is argued that knowledge about child
      specific and parental premises for developmentally supportive relationships is
      both applicable and necessary for therapists working with troubled children. The
      article, furthermore, argues that the parents' understanding of their child's
      behaviour and developmental characteristics is an obvious target when we face
      families with troubled children in therapy. The relevance and applicability of
      three fields of research; attachment, temperament and narrative development is
      explored and a model for applying knowledge from these fields in a family therapy
      context using participant observation and reflecting dialogues is presented.

PMID- 21949048
TI  - Incorporating electronic monitoring feedback into clinical care: a novel and
      promising adherence promotion approach.
AB  - This paper presents case examples that document the preliminary clinical utility
      of using electronic monitoring (EM) feedback to tailor empirically validated
      adherence-promoting interventions, delivered in standard clinical practice.
      Challenges of utilizing EM in standard clinical practice as well as future
      directions are also discussed. Two adolescents referred for behavioral adherence
      promotion intervention are described. Each youth was provided a MEMS(r) bottle
      and one oral medication was chosen jointly by the therapist, family, and medical
      provider for adherence monitoring. Graphical MEMS(r) feedback was provided to
      families during intervention visits and subsequently used to tailor adherence
      interventions to target each family's unique needs. EM feedback was a feasible
      and clinically rich supplement to adherence-promoting interventions. EM
      facilitated identification of adherence barriers and successes, and open and non
      adversarial discussions regarding adherence between patients, families, and
      clinicians, and provided real-time representations of patients' medication
      administration. These case presentations suggest that EM feedback can be a
      clinically useful tool when used as a supplement to an empirically supported
      intervention delivered in standard psychological practice aimed at adherence
      promotion among chronically ill youth.

PMID- 21949049
TI  - Interaction of PPARG Pro12Ala with dietary fat influences plasma lipids in
      subjects at cardiometabolic risk.
AB  - The PPARgamma2 gene single nucleotide polymorphism (SNP) Pro12Ala has shown
      variable association with metabolic syndrome traits in healthy subjects. The
      RISCK Study investigated the effect of interaction between genotype and the ratio
      of polyunsaturated:saturated (P:S) fatty acid intake on plasma lipids in 367
      white subjects (ages 30-70 years) at increased cardiometabolic risk. Interaction
      was determined after habitual diet at recruitment, at baseline after a 4-week
      high-SFA (HS) diet, and after a 24-week reference (HS), high-MUFA (HM), or low
      fat (LF) diet. At recruitment, there were no significant associations between
      genotype and plasma lipids; however, P:S * genotype interaction influenced plasma
      total cholesterol (TC) (P = 0.02), LDL-cholesterol (LDL-C) (P = 0.002), and
      triglyceride (TG) (P = 0.02) concentrations. At P:S ratio <= 0.33, mean TC and
      LDL-C concentrations in Ala12 allele carriers were significantly higher than in
      noncarriers (respectively, P = 0.003; P = 0.0001). Significant trends in
      reduction of plasma TC (P = 0.02) and TG (P = 0.002) concentrations occurred with
      increasing P:S (respectively, <=0.33 to >0.65; 0.34 to >0.65) in Ala12 allele
      carriers. There were no significant differences between carriers and noncarriers
      after the 4-week HS diet or 24-week interventions. Plasma TC and TG
      concentrations in PPARG Ala12 allele carriers decrease as P:S increases, but they
      are not dependent on a reduction in SFA intake.

PMID- 21949050
TI  - Dissociation of diabetes and obesity in mice lacking orphan nuclear receptor
      small heterodimer partner.
AB  - Mixed background SHP(-/-) mice are resistant to diet-induced obesity due to
      increased energy expenditure caused by enhanced PGC-1alpha expression in brown
      adipocytes. However, congenic SHP(-/-) mice on the C57BL/6 background showed
      normal expression of PGC-1alpha and other genes involved in brown adipose tissue
      thermogenesis. Thus, we reinvestigated the impact of small heterodimer partner
      (SHP) deletion on diet-induced obesity and insulin resistance using congenic SHP(
      /-) mice. Compared with their C57BL/6 wild-type counterparts, SHP(-/-) mice
      subjected to a 6 month challenge with a Western diet (WestD) were leaner but more
      glucose intolerant, showed hepatic insulin resistance despite decreased
      triglyceride accumulation and increased beta-oxidation, exhibited alterations in
      peripheral tissue uptake of dietary lipids, maintained a higher respiratory
      quotient, which did not decrease even after WestD feeding, and displayed islet
      dysfunction. Hepatic mRNA expression analysis revealed that many genes expressed
      higher in SHP(-/-) mice fed WestD were direct peroxisome proliferator-activated
      receptor alpha (PPARalpha) targets. Indeed, transient transfection and chromatin
      immunoprecipitation verified that SHP strongly repressed PPARalpha-mediated
      transactivation. SHP is a pivotal metabolic sensor controlling lipid homeostasis
      in response to an energy-laden diet through regulating PPARalpha-mediated
      transactivation. The resultant hepatic fatty acid oxidation enhancement and
      dietary fat redistribution protect the mice from diet-induced obesity and hepatic
      steatosis but accelerate development of type 2 diabetes.

PMID- 21949052
TI  - Vortex beams for atomic resolution dichroism.
AB  - Vortex beams carrying orbital angular momentum have been produced recently with
      electron microscopy by interfering an incident electron beam with a grid
      containing dislocations. Here, we present an analytical derivation of vortex wave
      functions in reciprocal and real space. We outline their mathematical and
      physical properties and describe the conditions under which vortex beams can be
      used in scanning transmission microscopy to measure magnetic properties of
      materials at the atomic scale.

PMID- 21949051
TI  - Identification of cholesterol crystals in plaques of atherosclerotic mice using
      hyperspectral CARS imaging.
AB  - The accumulation of lipids, including cholesterol, in the arterial wall plays a
      key role in the pathogenesis of atherosclerosis. Although several advances have
      been made in the detection and imaging of these lipid structures in plaque
      lesions, their morphology and composition have yet to be fully elucidated,
      particularly in different animal models of disease. To address this issue, we
      analyzed lipid morphology and composition in the atherosclerotic plaques of two
      animal models of disease, the low density lipoprotein receptor-deficient (LDLR(-/
      )) mouse and the ApoE lipoprotein-deficient (ApoE(-/-)) mouse, utilizing
      hyperspectral coherent anti-Stokes Raman scattering (CARS) microscopy in
      combination with principal component analysis (PCA). Hyperspectral CARS imaging
      revealed lipid-rich macrophage cells and condensed needle-shaped and plate-shaped
      lipid crystal structures in both mice. Spectral analysis with PCA and comparison
      to spectra of pure cholesterol and cholesteryl ester derivatives further revealed
      these lipid structures to be pure cholesterol crystals, which were predominantly
      observed in the ApoE(-/-) mouse model. These results illustrate the ability of
      hyperspectral CARS imaging in combination with multivariate analysis to
      characterize atherosclerotic lipid morphology and composition with chemical
      specificity, and consequently, provide new insight into the formation of
      cholesterol crystal structures in atherosclerotic plaque lesions.

PMID- 21949053
TI  - How should political philosophers think of health?
AB  - The political philosophy of health care has been characterized by considerable
      conceptual inflation in recent years. First, the concept of health that lies at
      its core has come to encompass ever-increasing aspects of individuals'
      existences. And second, the emergence of the public health perspective has
      increased the range of resources relevant to health equity. This expansion has
      not been without cost. The decision to include more rather than less within the
      ambit of "health" is ultimately a moral/political rather than an ontological or
      metaphysical one, and there are several ethical reasons to define the scope of
      theories of distributive justice in health narrowly.

PMID- 21949054
TI  - Researchers and firing squads: questions concerning the use of frozen human
      embryos.
AB  - Is it morally acceptable to use human embryos left over from fertility treatments
      in research that would harm or destroy them? Many answer "no" to this question on
      the grounds that all human beings, including human embryos, have a basic moral
      status that forbids such use. There are some, though, who accept this claim about
      the basic moral status of human embryos but who believe nevertheless that frozen
      human embryos which were generated for fertility treatments but which are no
      longer wanted for that project are a morally acceptable source of human embryonic
      stem cells and are acceptable subjects of other forms of research that would
      destroy them in course. The reasoning offered in defense of this position
      typically employs the claim that since these embryos are going to be discarded
      anyway, their possibly fruitful use by researchers is a preferable alternative
      and one that is not inconsistent with their basic moral status. Howard Curzer has
      offered a well-developed argument of this sort, defending the use of these
      embryos in the ways mentioned while at the same time allowing for their equal
      basic moral status. This article challenges Curzer's case and offers reasons to
      reject the moral acceptability of using even these to-be-discarded embryos as
      research material.

PMID- 21949055
TI  - Internet users' perception of the importance of signs commonly seen in old
      animals with age-related diseases.

PMID- 21949056
TI  - Estimated prevalence of the GYS-1 mutation in healthy Austrian Haflingers.
AB  - The aim of this study was to determine the occurrence and frequency of a mutation
      in the gene coding for skeletal muscle glycogen synthase type 1 (GYS-1), which is
      the cause of equine polysaccharide storage myopathy (PSSM) type 1 in a population
      of 50 Haflingers. GYS-1 genotyping of 50 Haflingers was performed with a
      validated restriction fragment length polymorphism (RFLP) assay. The second aim
      was to compare resting and post-exercise muscle enzyme activities as well as
      parameters of glucose metabolism in blood between horses with and without the
      mutation. Nine of the 50 Haflingers were identified to be heterozygous for the
      mutation (HR). None was homozygous (HH). The estimated HR prevalence was 18 per
      cent in this herd. Mean aspartate aminotransferase (AST) activity at rest and
      mean creatine kinase and AST activity after exercise were significantly higher in
      HR compared with RR (homozygote normal) horses. No significant differences could
      be found in the other parameters.

PMID- 21949057
TI  - Computed tomographic demonstration of central tarsal bone plantar process occult
      fracture in a dog.

PMID- 21949058
TI  - Canine haemophilia A caused by a mutation leading to a stop codon.

PMID- 21949059
TI  - Metaphylactic gamithromycin treatment for the management of lameness in ewes
      putatively caused by Bacteroides melaninogenicus.

PMID- 21949060
TI  - Assessment of consciousness during propofol anaesthesia in pigs.

PMID- 21949061
TI  - Standards of practice for culturally competent nursing care: 2011 update.

PMID- 21949062
TI  - Development of the concentric sphere family environment model and companion tools
      for culturally congruent family assessment.
AB  - The article presents development of a nursing model for holistically
      understanding the family environment that acts on family well-being as well as of
      tools based on this model to assess family well-being. These were constructed by
      using qualitative, quantitative, and literary approaches, such as the Delphi
      technique, a literature review, semistructured interviews with families, and
      ethnographic studies in Japan, Hong Kong, and the United States. In the
      "Concentric Sphere Family Environment Model," a three-dimensional logical space
      is formed by the three assessment axes of relationships (structural distance,
      functional distance, and temporal distance) and five systems (supra system, macro
      system, micro system, family internal environment system, and chrono system)
      located therein. The "Family Environment Assessment Index" comprises 37 items for
      assessing the family well-being, and for each of their specifications useful
      sample questions are provided to conduct the culturally congruent family
      assessment.

PMID- 21949063
TI  - Identification of the amidotransferase AsnB1 as being responsible for meso
      diaminopimelic acid amidation in Lactobacillus plantarum peptidoglycan.
AB  - The peptidoglycan (PG) of Lactobacillus plantarum contains amidated meso
      diaminopimelic acid (mDAP). The functional role of this PG modification has never
      been characterized in any bacterial species, except for its impact on PG
      recognition by receptors of the innate immune system. In silico analysis of loci
      carrying PG biosynthesis genes in the L. plantarum genome revealed the
      colocalization of the murE gene, which encodes the ligase catalyzing the addition
      of mDAP to UDP-N-muramoyl-d-glutamate PG precursors, with asnB1, which encodes a
      putative asparagine synthase with an N-terminal amidotransferase domain. By gene
      disruption and complementation experiments, we showed that asnB1 is the
      amidotransferase involved in mDAP amidation. PG structural analysis revealed that
      mDAP amidation plays a key role in the control of the l,d-carboxypeptidase DacB
      activity. In addition, a mutant strain with a defect in mDAP amidation is
      strongly affected in growth and cell morphology, with filamentation and cell
      chaining, while a DacB-negative strain displays a phenotype very similar to that
      of a wild-type strain. These results suggest that mDAP amidation may play a
      critical role in the control of the septation process.

PMID- 21949064
TI  - Localization pattern of conjugation machinery in a Gram-positive bacterium.
AB  - Conjugation is an efficient way for transfer of genetic information between
      bacteria, even between highly diverged species, and a major cause for the
      spreading of resistance genes. We have investigated the subcellular localization
      of several conserved conjugation proteins carried on plasmid pLS20 found in
      Bacillus subtilis. We show that VirB1, VirB4, VirB11, VirD2, and VirD4 homologs
      assemble at a single cell pole, but also at other sites along the cell membrane,
      in cells during the lag phase of growth. Bimolecular fluorescence complementation
      analyses showed that VirB4 and VirD4 interact at the cell pole and, less
      frequently, at other sites along the membrane. VirB1 and VirB11 also colocalized
      at the cell pole. Total internal reflection fluorescence microscopy showed that
      pLS20 is largely membrane associated and is frequently found at the cell pole,
      indicating that transfer takes place at the pole, which is a preferred site for
      the assembly of the active conjugation apparatus, but not the sole site. VirD2,
      VirB4, and VirD4 started to localize to the pole or the membrane in stationary
      phase cells, and VirB1 and VirB11 were observed as foci in cells resuspended in
      fresh medium but no longer in cells that had entered exponential growth, although
      at least VirB4 was still expressed. These data reveal an unusual
      assembly/disassembly timing for the pLS20 conjugation machinery and suggest that
      specific localization of conjugation proteins in lag-phase cells and
      delocalization during growth are the reasons why pLS20 conjugation occurs only
      during early exponential phase.

PMID- 21949065
TI  - Analysis of the LIV system of Campylobacter jejuni reveals alternative roles for
      LivJ and LivK in commensalism beyond branched-chain amino acid transport.
AB  - Campylobacter jejuni is a leading cause of diarrheal disease in humans and an
      intestinal commensal in poultry and other agriculturally important animals. These
      zoonotic infections result in significant amounts of C. jejuni present in the
      food supply to contribute to disease in humans. We previously found that a
      transposon insertion in Cjj81176_1038, encoding a homolog of the Escherichia coli
      LivJ periplasmic binding protein of the leucine, isoleucine, and valine (LIV)
      branched-chain amino acid transport system, reduced the commensal colonization
      capacity of C. jejuni 81-176 in chicks. Cjj81176_1038 is the first gene of a six
      gene locus that encodes homologous components of the E. coli LIV system. By
      analyzing mutants with in-frame deletions of individual genes or pairs of genes,
      we found that this system constitutes a LIV transport system in C. jejuni
      responsible for a high level of leucine acquisition and, to a lesser extent,
      isoleucine and valine acquisition. Despite each LIV protein being required for
      branched-chain amino acid transport, only the LivJ and LivK periplasmic binding
      proteins were required for wild-type levels of commensal colonization of chicks.
      All LIV permease and ATPase components were dispensable for in vivo growth. These
      results suggest that the biological functions of LivJ and LivK for colonization
      are more complex than previously hypothesized and extend beyond a role for
      binding and acquiring branched-chain amino acids during commensalism. In contrast
      to other studies indicating a requirement and utilization of other specific amino
      acids for colonization, acquisition of branched-chain amino acids does not appear
      to be a determinant for C. jejuni during commensalism.

PMID- 21949066
TI  - Probing the impact of ligand binding on the acyl-homoserine lactone-hindered
      transcription factor EsaR of Pantoea stewartii subsp. stewartii.
AB  - The quorum-sensing regulator EsaR from Pantoea stewartii subsp. stewartii is a
      LuxR homologue that is inactivated by acyl-homoserine lactone (AHL). In the corn
      pathogen P. stewartii, production of exopolysaccharide (EPS) is repressed by EsaR
      at low cell densities. However, at high cell densities when high concentrations
      of its cognate AHL signal are present, EsaR is inactivated and derepression of
      EPS production occurs. Thus, EsaR responds to AHL in a manner opposite to that of
      most LuxR family members. Depending on the position of its binding site within
      target promoters, EsaR serves as either a repressor or activator in the absence
      rather than in the presence of its AHL ligand. The effect of AHL on LuxR
      homologues has been difficult to study in vitro because AHL is required for
      purification and stability. EsaR, however, can be purified without AHL enabling
      an in vitro analysis of the response of the protein to ligand. Western
      immunoblots and pulse-chase experiments demonstrated that EsaR is stable in vivo
      in the absence or presence of AHL. Limited in vitro proteolytic digestions of a
      biologically active His-MBP tagged version of EsaR highlighted intradomain and
      interdomain conformational changes that occur in the protein in response to AHL.
      Gel filtration chromatography of the full-length fusion protein and cross-linking
      of the N-terminal domain both suggest that this conformational change does not
      impact the multimeric state of the protein. These findings provide greater
      insight into the diverse mechanisms for AHL responsiveness found within the LuxR
      family.

PMID- 21949067
TI  - Just-in-time control of Spo0A synthesis in Bacillus subtilis by multiple
      regulatory mechanisms.
AB  - The response regulator Spo0A governs multiple developmental processes in Bacillus
      subtilis, including most conspicuously sporulation. Spo0A is activated by
      phosphorylation via a multicomponent phosphorelay. Previous work has shown that
      the Spo0A protein is not rate limiting for sporulation. Rather, Spo0A is present
      at high levels in growing cells, rapidly rising to yet higher levels under
      sporulation-inducing conditions, suggesting that synthesis of the response
      regulator is subject to a just-in-time control mechanism. Transcription of spo0A
      is governed by a promoter switching mechanism, involving a vegetative, sigma(A)
      recognized promoter, P(v), and a sporulation sigma(H)-recognized promoter, P(s),
      that is under phosphorylated Spo0A (Spo0A~P) control. The spo0A regulatory region
      also contains four (including one identified in the present work) conserved
      elements that conform to the consensus binding site for Spo0A~P binding sites.
      These are herein designated O(1), O(2), O(3), and O(4) in reverse order of their
      proximity to the coding sequence. Here we report that O(1) is responsible for
      repressing P(v) during the transition to stationary phase, that O(2) is
      responsible for repressing P(s) during growth, that O(3) is responsible for
      activating P(s) at the start of sporulation, and that O(4) is dispensable for
      promoter switching. We also report that Spo0A synthesis is subject to a
      posttranscriptional control mechanism such that translation of mRNAs originating
      from P(v) is impeded due to RNA secondary structure whereas mRNAs originating
      from P(s) are fully competent for protein synthesis. We propose that the opposing
      actions of O(2) and O(3) and the enhanced translatability of mRNAs originating
      from P(s) create a highly sensitive, self-reinforcing switch that is responsible
      for producing a burst of Spo0A synthesis at the start of sporulation.

PMID- 21949068
TI  - In Rhodobacter sphaeroides, chemotactic operon 1 regulates rotation of the
      flagellar system 2.
AB  - Rhodobacter sphaeroides is able to assemble two different flagella, the subpolar
      flagellum (Fla1) and the polar flagella (Fla2). In this work, we report the
      swimming behavior of R. sphaeroides Fla2(+) cells lacking each of the proteins
      encoded by chemotactic operon 1. A model proposing how these proteins control
      Fla2 rotation is presented.

PMID- 21949069
TI  - Tropodithietic acid production in Phaeobacter gallaeciensis is regulated by N
      acyl homoserine lactone-mediated quorum sensing.
AB  - The production of N-acyl homoserine lactones (AHLs) is widely distributed within
      the marine Roseobacter clade, and it was proposed that AHL-mediated quorum
      sensing (QS) is one of the most common cell-to-cell communication mechanisms in
      roseobacters. The traits regulated by AHL-mediated QS are yet not known for
      members of the Roseobacter clade, but production of the antibiotic tropodithietic
      acid (TDA) was supposed to be controlled by AHL-mediated QS in Phaeobacter spp.
      We describe here for the first time the functional role of luxR and luxI
      homologous genes of an organism of the Roseobacter clade, i.e., pgaR and pgaI in
      Phaeobacter gallaeciensis. Our results demonstrate that the AHL synthase gene
      pgaI is responsible for production of N-3-hydroxydecanoylhomoserine lactone
      (3OHC(10)-HSL). Insertion mutants of pgaI and pgaR are both deficient in TDA
      biosynthesis and the formation of a yellow-brown pigment when grown in liquid
      marine broth medium. This indicates that in P. gallaeciensis the production of
      both secondary metabolites is controlled by AHL-mediated QS. Quantitative real
      time PCR showed that the transcription level of tdaA, which encodes an essential
      transcriptional regulator for TDA biosynthesis, decreased 28- and 51-fold in pgaI
      and pgaR genetic backgrounds, respectively. These results suggest that both the
      response regulator PgaR and the 3OHC(10)-HSL produced by PgaI induce expression
      of tdaA, which in turn positively regulates expression of the tda genes.
      Moreover, we confirmed that TDA can also act as autoinducer in P. gallaeciensis,
      as previously described for Silicibacter sp. strain TM1040, but only in the
      presence of the response regulator PgaR.

PMID- 21949070
TI  - Role of Sphingomonas sp. strain Fr1 PhyR-NepR-sigmaEcfG cascade in general stress
      response and identification of a negative regulator of PhyR.
AB  - The general stress response in Alphaproteobacteria was recently described to
      depend on the alternative sigma factor sigma(EcfG), whose activity is regulated
      by its anti-sigma factor NepR. The response regulator PhyR, in turn, regulates
      NepR activity in a partner-switching mechanism according to which phosphorylation
      of PhyR triggers sequestration of NepR by the sigma factor-like effector domain
      of PhyR. Although genes encoding predicted histidine kinases can often be found
      associated with phyR, little is known about their role in modulation of PhyR
      phosphorylation status. We demonstrate here that the PhyR-NepR-sigma(EcfG)
      cascade is important for multiple stress resistance and competitiveness in the
      phyllosphere in a naturally abundant plant epiphyte, Sphingomonas sp. strain Fr1,
      and provide evidence that the partner switching mechanism is conserved. We
      furthermore identify a gene, designated phyP, encoding a predicted histidine
      kinase at the phyR locus as essential. Genetic epistasis experiments suggest that
      PhyP acts upstream of PhyR, keeping PhyR in an unphosphorylated, inactive state
      in nonstress conditions, strictly depending on the predicted phosphorylatable
      site of PhyP, His-341. In vitro experiments show that Escherichia coli inner
      membrane fractions containing PhyP disrupt the PhyR-P/NepR complex. Together with
      the fact that PhyP lacks an obvious ATPase domain, these results are in agreement
      with PhyP functioning as a phosphatase of PhyR, rather than a kinase.

PMID- 21949071
TI  - Surface layers of Clostridium difficile endospores.
AB  - Clostridium difficile is an important human pathogen and one where the primary
      cause of disease is due to the transmission of spores. We have investigated the
      proteins found in the outer coat layers of C. difficile spores of pathogenic
      strain 630 (CD630). Five coat proteins, CotA, CotB, CotCB, CotD, and CotE, were
      shown to be expressed on the outer coat layers of the spore. We demonstrate that
      purified spores carry catalase, peroxiredoxin, and chitinase activity and that
      this activity correlates with the predicted functions of three spore coat
      proteins identified here, CotCB, CotD, and CotE. CotCB and CotD are putative
      manganese catalases, and CotE is a novel bifunctional protein with peroxiredoxin
      activity at its amino terminus and chitinase activity at its carboxy terminus.
      These enzymes could play an important role in coat assembly by polymerizing
      protein monomers in the coat. CotE, in addition to a role in macromolecular
      degradation, could play an important role in inflammation, and this may be of
      direct relevance to the development of the gastrointestinal symptoms that
      accompany C. difficile infection. Although specific enzyme activity has not yet
      been assigned to the proteins identified here, this work provides the first
      detailed study of the C. difficile spore coat.

PMID- 21949072
TI  - Temperature-sensitive mutants of RNase E in Salmonella enterica.
AB  - RNase E has an important role in mRNA turnover and stable RNA processing,
      although the reason for its essentiality is unknown. We isolated conditional
      mutants of RNase E to provide genetic tools to probe its essential function. In
      Salmonella enterica serovar Typhimurium, an extreme slow-growth phenotype caused
      by mutant EF-Tu (Gln125Arg, tufA499) can be rescued by mutants of RNase E that
      have reduced activity. We exploited this phenotype to select mutations in RNase E
      and screened these for temperature sensitivity (TS) for growth. Four different TS
      mutations were identified, all in the N-terminal domain of RNase E: Gly66->Cys,
      Ile207->Ser, Ile207->Asn, and Ala327->Pro. We also selected second-site mutations
      in RNase E that reversed temperature sensitivity. The complete set of RNase E
      mutations (53 primary mutations including the TS mutations, and 23 double
      mutations) were analyzed for their possible effects on the structure and function
      of RNase E by using the available three-dimensional (3-D) structures. Most single
      mutations were predicted to destabilize the structure, while second-site
      mutations that reversed the TS phenotype were predicted to restore stability to
      the structure. Three isogenic strain pairs carrying single or double mutations in
      RNase E (TS, and TS plus second-site mutation) were tested for their effects on
      the degradation, accumulation, and processing of mRNA, rRNA, and tRNA. The
      greatest defect was observed on rne mRNA autoregulation, and this correlated with
      the ability to rescue the tufA499-associated slow-growth phenotype. This is
      consistent with the RNase E mutants being defective in initial binding or
      subsequent cleavage of an mRNA critical for fast growth.

PMID- 21949073
TI  - Physiological roles for two periplasmic nitrate reductases in Rhodobacter
      sphaeroides 2.4.3 (ATCC 17025).
AB  - The metabolically versatile purple bacterium Rhodobacter sphaeroides 2.4.3 is a
      denitrifier whose genome contains two periplasmic nitrate reductase-encoding gene
      clusters. This work demonstrates nonredundant physiological roles for these two
      enzymes. One cluster is expressed aerobically and repressed under low oxygen
      while the second is maximally expressed under low oxygen. Insertional
      inactivation of the aerobically expressed nitrate reductase eliminated aerobic
      nitrate reduction, but cells of this strain could still respire nitrate
      anaerobically. In contrast, when the anaerobic nitrate reductase was absent,
      aerobic nitrate reduction was detectable, but anaerobic nitrate reduction was
      impaired. The aerobic nitrate reductase was expressed but not utilized in liquid
      culture but was utilized during growth on solid medium. Growth on a variety of
      carbon sources, with the exception of malate, the most oxidized substrate used,
      resulted in nitrite production on solid medium. This is consistent with a role
      for the aerobic nitrate reductase in redox homeostasis. These results show that
      one of the nitrate reductases is specific for respiration and denitrification
      while the other likely plays a role in redox homeostasis during aerobic growth.

PMID- 21949074
TI  - Biochemical and cellular characterization of Helicobacter pylori RecA, a protein
      with high-level constitutive expression.
AB  - Helicobacter pylori is a bacterial pathogen colonizing half of the world's human
      population. It has been implicated in a number of gastric diseases, from
      asymptomatic gastritis to cancer. It is characterized by an amazing genetic
      variability that results from high mutation rates and efficient DNA homologous
      recombination and transformation systems. Here, we report the characterization of
      H. pylori RecA (HpRecA), a protein shown to be involved in DNA repair,
      transformation, and mouse colonization. The biochemical characterization of the
      purified recombinase reveals activities similar to those of Escherichia coli RecA
      (EcRecA). We show that in H. pylori, HpRecA is present in about 80,000 copies per
      cell during exponential growth and decreases to about 50,000 copies in stationary
      phase. The amount of HpRecA remains unchanged after induction of DNA lesions,
      suggesting that HpRecA is always expressed at a high level in order to repair DNA
      damage or facilitate recombination. We performed HpRecA localization analysis by
      adding a Flag tag to the protein, revealing two different patterns of
      localization. During exponential growth, RecA-Flag presents a diffuse pattern,
      overlapping with the DAPI (4',6-diamidino-2-phenylindole) staining of DNA,
      whereas during stationary phase, the protein is present in more defined areas
      devoid of DAPI staining. These localizations are not affected by inactivation of
      competence or DNA recombination genes. Neither UV irradiation nor gamma
      irradiation modified HpRecA localization, suggesting the existence of a
      constitutive DNA damage adaptation system.

PMID- 21949075
TI  - Whole-genome association study on tissue tropism phenotypes in group A
      Streptococcus.
AB  - Group A Streptococcus (GAS) has a rich evolutionary history of horizontal
      transfer among its core genes. Yet, despite extensive genetic mixing, GAS strains
      have discrete ecological phenotypes. To further our understanding of the
      molecular basis for ecological phenotypes, comparative genomic hybridization of a
      set of 97 diverse strains to a GAS pangenome microarray was undertaken, and the
      association of accessory genes with emm genotypes that define tissue tropisms for
      infection was determined. Of the 22 nonprophage accessory gene regions (AGRs)
      identified, only 3 account for all statistically significant linkage
      disequilibrium among strains having the genotypic biomarkers for throat versus
      skin infection specialists. Networked evolution and population structure analyses
      of loci representing each of the AGRs reveal that most strains with the skin
      specialist and generalist biomarkers form discrete clusters, whereas strains with
      the throat specialist biomarker are highly diverse. To identify coinherited and
      coselected accessory genes, the strength of genetic associations was determined
      for all possible pairwise combinations of accessory genes among the 97 GAS
      strains. Accessory genes showing very strong associations provide the basis for
      an evolutionary model, which reveals that a major transition between many throat
      and skin specialist haplotypes correlates with the gain or loss of genes encoding
      fibronectin-binding proteins. This study employs a novel synthesis of tools to
      help delineate the major genetic changes associated with key adaptive shifts in
      an extensively recombined bacterial species.

PMID- 21949076
TI  - VasH is a transcriptional regulator of the type VI secretion system functional in
      endemic and pandemic Vibrio cholerae.
AB  - The gram-negative bacterium Vibrio cholerae is the etiological agent of cholera,
      a disease characterized by the release of high volumes of watery diarrhea. Many
      medically important proteobacteria, including V. cholerae, carry one or multiple
      copies of the gene cluster that encodes the bacterial type VI secretion system
      (T6SS) to confer virulence or interspecies competitiveness. Structural similarity
      and sequence homology between components of the T6SS and the cell-puncturing
      device of T4 bacteriophage suggest that the T6SS functions as a molecular syringe
      to inject effector molecules into prokaryotic and eukaryotic target cells.
      Although our understanding of how the structural T6SS apparatus assembles is
      developing, little is known about how this system is regulated. Here, we report
      on the contribution of the activator of the alternative sigma factor 54, VasH, as
      a global regulator of the V. cholerae T6SS. Using bioinformatics and mutational
      analyses, we identified domains of the VasH polypeptide that are essential for
      its ability to initiate transcription of T6SS genes and established a universal
      role for VasH in endemic and pandemic V. cholerae strains.

PMID- 21949077
TI  - Functional characterization of the RuvB homologs from Mycoplasma pneumoniae and
      Mycoplasma genitalium.
AB  - Homologous recombination between repeated DNA elements in the genomes of
      Mycoplasma species has been hypothesized to be a crucial causal factor in
      sequence variation of antigenic proteins at the bacterial surface. To investigate
      this notion, studies were initiated to identify and characterize the proteins
      that form part of the homologous DNA recombination machinery in Mycoplasma
      pneumoniae as well as Mycoplasma genitalium. Among the most likely participants
      of this machinery are homologs of the Holliday junction migration motor protein
      RuvB. In both M. pneumoniae and M. genitalium, genes have been identified that
      have the capacity to encode RuvB homologs (MPN536 and MG359, respectively). Here,
      the characteristics of the MPN536- and MG359-encoded proteins (the RuvB proteins
      from M. pneumoniae strain FH [RuvB(FH)] and M. genitalium [RuvB(Mge)],
      respectively) are described. Both RuvB(FH) and RuvB(Mge) were found to have
      ATPase activity and to bind DNA. In addition, both proteins displayed divalent
      cation- and ATP-dependent DNA helicase activity on partially double-stranded DNA
      substrates. The helicase activity of RuvB(Mge), however, was significantly lower
      than that of RuvB(FH). Interestingly, we found RuvB(FH) to be expressed
      exclusively by subtype 2 strains of M. pneumoniae. In strains belonging to the
      other major subtype (subtype 1), a version of the protein is expressed (the RuvB
      protein from M. pneumoniae strain M129 [RuvB(M129)]) that differs from RuvB(FH)
      in a single amino acid residue (at position 140). In contrast to RuvB(FH),
      RuvB(M129) displayed only marginal levels of DNA-unwinding activity. These
      results demonstrate that M. pneumoniae strains (as well as closely related
      Mycoplasma spp.) can differ significantly in the function of components of their
      DNA recombination and repair machinery.

PMID- 21949078
TI  - SagS contributes to the motile-sessile switch and acts in concert with BfiSR to
      enable Pseudomonas aeruginosa biofilm formation.
AB  - The interaction of Pseudomonas aeruginosa with surfaces has been described as a
      two-stage process requiring distinct signaling events and the reciprocal
      modulation of small RNAs (sRNAs). However, little is known regarding the
      relationship between sRNA-modulating pathways active under planktonic or surface
      associated growth conditions. Here, we demonstrate that SagS (PA2824), the
      cognate sensor of HptB, links sRNA-modulating activities via the Gac/HptB/Rsm
      system postattachment to the signal transduction network BfiSR, previously
      demonstrated to be required for the development of P. aeruginosa. Consistent with
      the role of SagS in the GacA-dependent HtpB signaling pathway, inactivation of
      sagS resulted in hyperattachment, an HptB-dependent increase in rsmYZ, increased
      Psl polysaccharide production, and increased virulence. Moreover, sagS
      inactivation rescued attachment but abrogated biofilm formation by the DeltagacA
      and DeltahptB mutant strains. The DeltasagS strain was impaired in biofilm
      formation at a stage similar to that of the previously described two-component
      system BfiSR. Expression of bfiR but not bfiS restored DeltasagS biofilm
      formation independently of rsmYZ. We demonstrate that SagS interacts directly
      with BfiS and only indirectly with BfiR, with the direct and specific interaction
      between these two membrane-bound sensors resulting in the modulation of the
      phosphorylation state of BfiS in a growth-mode-dependent manner. SagS plays an
      important role in P. aeruginosa virulence in a manner opposite to that of BfiS.
      Our findings indicate that SagS acts as a switch by linking the GacA-dependent
      sensory system under planktonic conditions to the suppression of sRNAs
      postattachment and to BfiSR, required for the development of P. aeruginosa
      biofilms, in a sequential and stage-specific manner.

PMID- 21949079
TI  - FraH is required for reorganization of intracellular membranes during heterocyst
      differentiation in Anabaena sp. strain PCC 7120.
AB  - In the filamentous, heterocyst-forming cyanobacteria, two different cell types,
      the CO(2)-fixing vegetative cells and the N(2)-fixing heterocysts, exchange
      nutrients and regulators for diazotrophic growth. In the model organism Anabaena
      sp. strain PCC 7120, inactivation of fraH produces filament fragmentation under
      conditions of combined nitrogen deprivation, releasing numerous isolated
      heterocysts. Transmission electron microscopy of samples prepared by either high
      pressure cryo-fixation or chemical fixation showed that the heterocysts of a
      DeltafraH mutant lack the intracellular membrane system structured close to the
      heterocyst poles, known as the honeycomb, that is characteristic of wild-type
      heterocysts. Using a green fluorescent protein translational fusion to the
      carboxyl terminus of FraH (FraH-C-GFP), confocal microscopy showed spots of
      fluorescence located at the periphery of the vegetative cells in filaments grown
      in the presence of nitrate. After incubation in the absence of combined nitrogen,
      localization of FraH-C-GFP changed substantially, and the GFP fluorescence was
      conspicuously located at the cell poles in the heterocysts. Fluorescence
      microscopy and deconvolution of images showed that GFP fluorescence originated
      mainly from the region next to the cyanophycin plug present at the heterocyst
      poles. Intercellular transfer of the fluorescent tracers calcein (622 Da) and 5
      carboxyfluorescein (374 Da) was either not impaired or only partially impaired in
      the DeltafraH mutant, suggesting that FraH is not important for intercellular
      molecular exchange. Location of FraH close to the honeycomb membrane structure
      and lack of such structure in the DeltafraH mutant suggest a role of FraH in
      reorganization of intracellular membranes, which may involve generation of new
      membranes, during heterocyst differentiation.

PMID- 21949080
TI  - Peroxide stimulon and role of PerR in group A Streptococcus.
AB  - We have characterized group A Streptococcus (GAS) genome-wide responses to
      hydrogen peroxide and assessed the role of the peroxide response regulator (PerR)
      in GAS under oxidative stress. Comparison of transcriptome changes elicited by
      peroxide in wild-type bacteria with those in a perR deletion mutant showed that
      76 out of 237 peroxide-regulated genes are PerR dependent. Unlike the PerR
      mediated upregulation of peroxidases and other peroxide stress defense mechanisms
      previously reported in gram-positive species, PerR-dependent genes in GAS were
      almost exclusively downregulated and encoded proteins involved in purine and
      deoxyribonucleotide biosynthesis, heme uptake, and amino acid/peptide transport,
      but they also included a strongly activated putative transcriptional regulator
      (SPy1198). Of the 161 PerR-independent loci, repressed genes (86 of 161) encoded
      proteins with functions similar to those coordinated by PerR, in contrast to
      upregulated loci that encoded proteins that function in DNA damage repair,
      cofactor metabolism, reactive oxygen species detoxification, pilus biosynthesis,
      and hypothetical proteins. Complementation of the perR deletion mutant with wild
      type PerR restored PerR-dependent regulation, whereas complementation with either
      one of two PerR variants carrying single mutations in two predicted metal-binding
      sites did not rescue the mutant phenotype. Metal content analyses of the
      recombinant wild type and respective PerR mutants, in addition to regulation
      studies in metal-supplemented and iron-depleted media, showed binding of zinc and
      iron by PerR and an iron requirement for optimal responses to peroxide. Our
      findings reveal a novel physiological contribution of PerR in coordinating DNA
      and protein metabolic functions in peroxide and identify GAS adaptive responses
      that may serve to enhance oxidative stress resistance and virulence in the host.

PMID- 21949082
TI  - Oncology micro-cap stocks: caveat emptor!

PMID- 21949081
TI  - Company stock prices before and after public announcements related to oncology
      drugs.
AB  - BACKGROUND: Phase III clinical trials and Food and Drug Administration (FDA)
      regulatory decisions are critical for success of new drugs and can influence a
      company's market valuation. Knowledge of trial results before they are made
      public (ie, "inside information") can affect the price of a drug company's stock.
      We examined the stock prices of companies before and after public announcements
      regarding experimental anticancer drugs owned by the companies. METHODS: We
      identified drugs that were undergoing evaluation in phase III trials or for
      regulatory approval by the US FDA from January 2000 to January 2009. Stock prices
      of companies that owned such drugs were analyzed for 120 trading days before and
      after the first public announcement of 1) results of clinical trials with
      positive and negative outcomes and 2) positive and negative regulatory decisions.
      All statistical tests were two-sided. RESULTS: We identified public announcements
      from 23 positive trials and 36 negative trials and from 41 positive and nine
      negative FDA regulatory decisions. The mean stock price for the 120 trading days
      before a phase III clinical trial announcement increased by 13.7% (95% confidence
      interval = -2.2% to 29.6%) for companies that reported positive trials and
      decreased by 0.7% (95% confidence interval = -13.8% to 12.3%) for companies that
      reported negative trials (P = .09). In a post hoc analysis comparing the stock
      price averaged over 60 trading days before and after day -60 relative to the
      clinical trial announcement, the mean stock price increased by 9.4% for companies
      that reported positive trials and decreased by 4.5% for companies that reported
      negative trials (P = .03). Changes in company stock prices before FDA regulatory
      decisions did not differ statistically between companies with positive decision
      and companies with negative decisions. CONCLUSIONS: Trends in company stock
      prices before the first public announcement differ for companies that report
      positive vs negative trials. This finding has important legal and ethical
      implications for investigators, drug companies, and the investment industry.

PMID- 21949084
TI  - Dystocia in a cat due to an ectopic artery.

PMID- 21949083
TI  - Use of an avirulent live Salmonella Choleraesuis vaccine to reduce the prevalence
      of Salmonella carrier pigs at slaughter.
AB  - This study evaluated the use of an avirulent live Salmonella Choleraesuis vaccine
      to reduce the seroprevalence and number of Salmonella carrier pigs at slaughter.
      Seven batches of 500 pigs were included in each of the two study groups: the
      vaccinated group (VG) that was orally vaccinated and the control group (CG) that
      received a placebo on the first day of life. The groups were managed in a three
      site system and followed up from birth to slaughter. Blood samples (n=378) were
      collected from each VG and CG to monitor the on-farm seroprevalence in both
      groups. Mesenteric lymph nodes and blood from animals (n=390) belonging to each
      group were collected at slaughter. At the first day of life, the seroprevalence
      in control batches ranged from 77.9 to 96.3 per cent, while in vaccinated
      batches, it ranged from 66.6 to 92.6 per cent. At weaning (21 days of age), the
      number of seropositives decreased in both groups (mean of 12 and 3.7 per cent for
      CG and VG, respectively). At slaughter, batches of VG had a significantly
      (P<0.0001) lower seroprevalence (46.6+/-5 per cent) and isolation of Salmonella
      from lymph nodes (33.1+/-5 per cent) compared with CG batches (79.7+/-4 per cent
      and 59.5+/-5 per cent, respectively). The results indicate that administration of
      a Salmonella choleraesuis-attenuated vaccine on the first day of life decreases
      Salmonella isolation and seroprevalence in pigs at slaughter.

PMID- 21949086
TI  - Fibrosing myopathy of the temporal muscles causing lockjaw in a veiled chameleon
      (Chamaeleo calyptratus).

PMID- 21949085
TI  - Steroid-responsive meningitis-arteritis with spontaneous echocardiographic
      contrast and elevated cardiac troponin I in a dog.

PMID- 21949087
TI  - Effect of fenugreek seeds extract on cyclophosphamide-induced
      histomorphometrical, ultrastructural and biochemical changes in testes of albino
      mice.
AB  - Cyclophosphamide (CPA) is an anticancer drug used in the treatment of a variety
      of neoplastic lesions. On the other hand, treatment with CPA was accompanied by
      different toxic effects on different body organs. The present work was conducted
      to study the effect of fenugreek seed extract on histomorphometrical and
      ultrastructural changes induced by CPA in testes of albino mice. Twenty animals
      were given CPA (7.0 mg/kg body weight) three times/week orally for 8 weeks and
      were killed after 4 and 8 weeks. Testis of CPA-treated mice showed many
      histological alterations including appearance of irregular seminiferous tubules,
      reduction in the number of all spermatogenic cells, degeneration of Leydig cells
      and appearance of intertubular hemorrhage. Concerning the ultrastructural
      changes, abnormalities in spermatogonia (A and B), spermatocytes, round and
      elongated spermatids were observed. Degenerated Sertoli cells and degenerated
      interstitial tissue with abnormal Leydig cells were also seen. Moreover,
      administration of CPA to animals significantly increased malondialdehyde (MDA,
      lipid peroxidation marker) and decreased superoxide dismutase (SOD) and catalase
      (CAT). These changes were time-dependent. Treating animals with CPA and fenugreek
      seed extract (0.4 g/kg body weight) led to an improvement in the histological and
      ultrastructural pictures of the testis together with reduction in the level of
      serum MDA and increase in the activities of serum SOD and CAT. In conclusion, the
      results of the present work indicated that fenugreek had ameliorative effect
      against testis damage induced by CPA and this may be mediated by its potent
      antioxidant activities.

PMID- 21949088
TI  - The impact of heavy metals on the activity of carbonic anhydrase from rainbow
      trout (Oncorhynchus mykiss) kidney.
AB  - Many environmental and health problems have become a consequence of contamination
      of soil and water by toxic heavy metals and organic pollutants in the present age
      of technology. Heavy metals play vital roles in enzyme activities and other
      metabolic events with their bioaccumulative and nonbiodegradable properties among
      aquatic pollutants. Metal toxicity causes irregular metallothioneins protein
      synthesis, renal damage, and disruption of bone structure in humans and wildlife.
      In this study, we investigated in vitro effects of some metals on chemical
      targeted carbonic anhydrase (CA) enzyme from rainbow trout kidney. The enzyme was
      purified with a specific activity of 17,285 EU * mg(-1) and 31.7% yield and
      approximately 1800-fold using simple affinity purification method. Molecular
      weights of the subunit and native enzyme were estimated as 28.7 kDa and 26.9 kDa
      via sodium dodecyl sulfate polyacrylamide gel electrophoresis and Sephadex-G 200
      column, respectively. Other kinetic properties of the enzyme were determined.
      Apparent K(m) , V (max) and k (cat) values were 0.40 mM, 0.097 umol min(-1) and
      15.2 s(-1) for p-nitrophenylacetate substrate, respectively. Inhibitory effects
      of cobalt, zinc, copper, cadmium and silver on CA activity were determined using
      the esterase method under in vitro conditions. IC(50) and K(i) values were
      calculated for metals. K(i) values for Co(2+), Zn(2+), Cu(2+), Cd(2+) and Ag(+)
      were 0.035, 1.2, 34.8, 103 and 257 from Lineweaver-Burk graphs, respectively.
      Consequently, in vitro inhibition rank order was determined as Co(2+) > Zn(2+) >
      Cu(2+) > Cd(2+) > Ag(+). The potential inhibitor for CA was found as Co(2+) from
      these results.

PMID- 21949089
TI  - Cytotoxicity of the venom from the nematocysts of jellyfish Cyanea nozakii
      Kishinouye.
AB  - In this article, the cytotoxicity of the venom from the nematocysts of jellyfish
      Cyanea nozakii Kishinouye on human hepatoma cells (Bel-7402, SMMC-7721) and human
      colon cancer cells (H630) was investigated first. Of the three kinds of cells,
      the venom had the strongest cytotoxicity on H630 cells with the 50% lethal
      concentration (IC(50)) of 5.1 MUg/ml. However, the IC(50) on Bel-7402 and SMMC
      7721 was approximate 17.9 and 24.3 MUg/ml, respectively. The cytotoxicity of the
      venom was affected by pH, temperature and storage conditions. At the pH 4.5-8.5,
      the venom displayed obvious cytotoxicity and the percentage of survival was about
      50%. When pre-incubated at temperatures over 60 degrees C for as short as 10 min,
      the percentage of survival sharply improved from 4.6% up to 80%. The venom was
      stored in a more stable condition at -80 degrees C and in lyophilized state
      compared to other storage conditions used in this study. Lactate dehydrogenase
      release assay performed on H630 cells indicated that exposure to the venom could
      result in damage to the cell membrane.

PMID- 21949090
TI  - Effect of sublethal dose of mercury toxicity on liver cells and tissue of
      yellowfin seabream.
AB  - The aim of the present study was to provide baseline data on the prevalence of
      histopathological liver lesions in Acanthopagrus latus under experimental mercury
      exposure. Experimental study was at seawater recirculatory tanks. Mercury
      concentrations were determined using a standard cold vapour atomic absorption.
      Histopathological analyses were done in tissue processor and the slides were
      stained with haematoxylin and counterstained with eosin. There were many liver
      lesions including enlarged and lateral nuclei, nuclear degeneration and
      vacuolation; oncotic, apoptic, focal, massive, centrilobular and periportal
      necrosis; atrophy, lipidosis, hydropic and cloudy swelling, oval cell
      proliferation; bile stagnation, dilation of sinusoid, intracellular oedema and
      dark granules in both field and laboratory conditions. In conclusion the present
      investigation indicated that mercury is a toxic substance in yellowfin seabream
      and the sublethal concentrations of mercury may cause several changes in the
      histological indices of the studied fish, and we can use these changes as
      biomarkers of mercury detection.

PMID- 21949091
TI  - Effects of an individualized caregiver training intervention on self-efficacy of
      cancer caregivers.
AB  - Caring for older cancer patients after hospital discharge is challenging and many
      of their caregivers lack confidence to do so. This study investigated the effects
      of an individualized caregiver training program on self-efficacy in home care and
      symptom management. A total of 120 patient-caregiver dyads were randomly assigned
      to either the treatment (n = 60) or control group (n = 60). The training focused
      on prevention of infection, pain control, maintenance of nutrition and adequate
      elimination, and specific care issues identified by the caregiver. Control group
      received information about community-based resources. Results revealed a
      significant increase in self-efficacy after the training in the treatment group
      but not in the control group. No intervention effect was seen on caregiver's
      psychological well-being (depression, anxiety, and quality of life) and patient's
      physical symptoms.

PMID- 21949092
TI  - Glcci1 deficiency leads to proteinuria.
AB  - Unbiased transcriptome profiling and functional genomics approaches identified
      glucocorticoid-induced transcript 1 (GLCCI1) as being a transcript highly
      specific for the glomerulus, but its role in glomerular development and disease
      is unknown. Here, we report that mouse glomeruli express far greater amounts of
      Glcci1 protein compared with the rest of the kidney. RT-PCR and Western blotting
      demonstrated that mouse glomerular Glcci1 is approximately 60 kD and localizes to
      the cytoplasm of podocytes in mature glomeruli. In the fetal kidney, intense
      Glcci1 expression occurs at the capillary-loop stage of glomerular development.
      Using gene knockdown in zebrafish with morpholinos, morphants lacking Glcci1
      function had collapsed glomeruli with foot-process effacement. Permeability
      studies of the glomerular filtration barrier in these zebrafish morphants
      demonstrated a disruption of the selective glomerular permeability filter. Taken
      together, these data suggest that Glcci1 promotes the normal development and
      maintenance of podocyte structure and function.

PMID- 21949093
TI  - The pathophysiology of IgA nephropathy.
AB  - Here we discuss recent advances in understanding the biochemical, immunologic,
      and genetic pathogenesis of IgA nephropathy, the most common primary
      glomerulonephritis. Current data indicate that at least four processes contribute
      to development of IgA nephropathy. Patients with IgA nephropathy often have a
      genetically determined increase in circulating levels of IgA1 with galactose
      deficient O-glycans in the hinge-region (Hit 1). This glycosylation aberrancy is,
      however, not sufficient to induce renal injury. Synthesis and binding of
      antibodies directed against galactose-deficient IgA1 are required for formation
      of immune complexes that accumulate in the glomerular mesangium (Hits 2 and 3).
      These immune complexes activate mesangial cells, inducing proliferation and
      secretion of extracellular matrix, cytokines, and chemokines, which result in
      renal injury (Hit 4). Recent genome-wide association studies identify five
      distinct susceptibility loci--in the MHC on chromosome 6p21, the complement
      factor H locus on chromosome 1q32, and in a cluster of genes on chromosome 22q22-
      that potentially influence these processes and contain candidate mediators of
      disease. The significant variation in prevalence of risk alleles among different
      populations may also explain some of the sizable geographic variation in disease
      prevalence. Elucidation of the pathogenesis of IgA nephropathy provides an
      opportunity to develop disease-specific therapies.

PMID- 21949094
TI  - IL-33 exacerbates acute kidney injury.
AB  - Inflammation contributes to the pathogenesis of acute kidney injury (AKI). IL-33
      is a proinflammatory cytokine, but its role in AKI is unknown. Here we observed
      increased protein expression of full-length IL-33 in the kidney following
      induction of AKI with cisplatin. To determine whether IL-33 promotes injury, we
      administered soluble ST2 (sST2), a fusion protein that neutralizes IL-33 activity
      by acting as a decoy receptor. Compared with cisplatin-induced AKI in untreated
      mice, mice treated with sST2 had fewer CD4 T cells infiltrate the kidney, lower
      serum creatinine, and reduced acute tubular necrosis (ATN) and apoptosis. In
      contrast, administration of recombinant IL-33 (rIL-33) exacerbated cisplatin
      induced AKI, measured by an increase in CD4 T cell infiltration, serum
      creatinine, ATN, and apoptosis; this did not occur in CD4-deficient mice,
      suggesting that CD4 T cells mediate the injurious effect of IL-33. Wildtype mice
      that received cisplatin and rIL-33 also had higher levels of the proinflammatory
      chemokine CXCL1, which CD T cells produce, in the kidney compared with CD4
      deficient mice. Mice deficient in the CXCL1 receptor also had lower serum
      creatinine, ATN, and apoptosis than wildtype mice following cisplatin-induced
      AKI. Taken together, IL-33 promotes AKI through CD4 T cell-mediated production of
      CXCL1. These data suggest that inhibiting IL-33 or CXCL1 may have therapeutic
      potential in AKI.

PMID- 21949095
TI  - Mdm2 promotes systemic lupus erythematosus and lupus nephritis.
AB  - Systemic lupus erythematosus (SLE) is a polyclonal autoimmune syndrome directed
      against multiple nuclear autoantigens. Although RNA and DNA seem to have
      identical immunostimulatory effects on systemic and intrarenal inflammation, each
      seems to differ with regard to the propensity to induce mitogenic effects such as
      lymphoproliferation. To identify potential mechanisms by which DNA specifically
      contributes to the pathogenesis of lupus nephritis, we stimulated cells with
      immunostimulatory DNA or RNA in vitro and used microarray to compare the
      transcriptomes of RNA- and DNA-induced genes. Immunostimulatory DNA, but not RNA,
      induced Mdm2, which is a negative regulator of p53. In vivo, we observed greater
      expression and activation of Mdm2 in the spleen and kidneys in a mouse model of
      lupus (MRL-Fas(lpr) mice) than healthy controls. Treatment of MRL-Fas(lpr) mice
      with the Mdm2 inhibitor nutlin-3a prevented nephritis and lung disease and
      significantly prolonged survival. Inhibition of Mdm2 reduced systemic
      inflammation and abrogated immune complex disease by suppressing plasma cells and
      the production of lupus autoantibodies. In addition, nutlin-3a suppressed the
      abnormal expansion of all T cell subsets, including CD3(+)CD4(-)CD8(-) T cells,
      which associated with attenuated systemic inflammation. However, inhibiting Mdm2
      did not cause myelosuppression or affect splenic regulatory T cells, neutrophils,
      dendritic cells, or monocytes. Taken together, these data suggest that the
      induction of Mdm2 promotes the expansion of plasma cells and CD3(+)CD4(-)CD8(-) T
      cells, which cause autoantibody production and immune complex disease in MRL
      Fas(lpr) mice. Antagonizing Mdm2 may have therapeutic potential in lupus
      nephritis.

PMID- 21949103
TI  - Contamination with gangliosides in brain-derived rabies vaccine may trigger
      Guillain--Barre syndrome.

PMID- 21949096
TI  - Meta-analysis of calcineurin-inhibitor-sparing regimens in kidney
      transplantation.
AB  - Calcineurin-inhibitor-sparing strategies in kidney transplantation may spare
      patients the adverse effects of these drugs, but the efficacy of these strategies
      is unknown. Here, we conduct a meta-analysis to assess outcomes associated with
      reducing calcineurin inhibitor exposure from the time of transplantation. We
      search Medline, Embase, and Cochrane Register of Controlled Trials for randomized
      controlled trials published between 1966 and 2010 that compared de novo
      calcineurin-inhibitor-sparing regimens to calcineurin-inhibitor-based regimens.
      In this analysis, we include 56 studies comprising data from 11337 renal
      transplant recipients. Use of the contemporary agents belatacept or tofacitinib,
      in combination with mycophenolate, decreased the odds of overall graft failure
      (OR 0.61; 95% CI 0.39-0.96; P = 0.03). Similarly, minimization of calcineurin
      inhibitors in combination with various induction and adjunctive agents reduces
      the odds of graft failure (OR 0.73; 95% CI 0.58-0.92; P = 0.009). Conversely, the
      use of inhibitors of mammalian target of rapamycin (mTOR), in combination with
      mycophenolate, increases the odds of graft failure (OR 1.43; 95% CI 1.08-1.90; P
      = 0.01). Calcineurin-inhibitor-sparing strategies are associated with less
      delayed graft function (OR 0.89; 95% CI 0.80-0.98; P = 0.02), improved graft
      function, and less new-onset diabetes. The more contemporary protocols did not
      seem to increase rates of acute rejection. In conclusion, this meta-analysis
      suggests that reducing exposure to calcineurin inhibitors immediately after
      kidney transplantation may improve clinical outcomes.

PMID- 21949104
TI  - Optinurin inclusions in proximal hereditary motor and sensory neuropathy (HMSN
      P): familial amyotrophic lateral sclerosis with sensory neuronopathy?

PMID- 21949105
TI  - Pallidal deep brain stimulation for DYT6 dystonia.
AB  - BACKGROUND: Mutations of the THAP1 gene were recently shown to underlie DYT6
      torsion dystonia. Little is known about the response of this dystonia subtype to
      deep brain stimulation (DBS) at the internal globus pallidus (GPi). METHODS:
      Retrospective analysis of the medical records of three DYT6 patients who
      underwent pallidal DBS by one surgical team. The Burke-Fahn-Marsden Dystonia
      Rating scale served as the primary outcome measure. Comparison is made to 23
      patients with DYT1 dystonia also treated with GPi-DBS by the same team. RESULTS:
      In contrast with the DYT1 patients who exhibited a robust and sustained clinical
      response to DBS, the DYT6 patients exhibited more modest gains during the first 2
      years of therapy, and some symptom regression between years 2 and 3 despite
      adjustments to the stimulation parameters and repositioning of one stimulating
      lead. Microelectrode recordings made during the DBS procedures demonstrated no
      differences in the firing patterns of GPi neurons from DYT1 and DYT6 patients.
      DISCUSSION: Discovery of the genetic mutations responsible for the DYT6 phenotype
      allows for screening and analysis of a new homogeneous group of dystonia
      patients. DYT6 patients appear to respond less robustly to GPi-DBS than their
      DYT1 counterparts, most likely reflecting differences in the underlying
      pathophysiology of these distinct genetic disorders. CONCLUSIONS: While early
      results of pallidal DBS for DYT6 dystonia are encouraging, further research and
      additional subjects are needed both to optimise stimulation parameters for this
      population and to elucidate more accurately their response to surgical treatment.

PMID- 21949106
TI  - Convergence spasm in conversion disorders: prevalence in psychogenic and other
      movement disorders compared with controls.
AB  - BACKGROUND: Convergence spasm refers to transient ocular convergence, miosis and
      accommodation associated with disconjugate gaze mimicking abducens palsy. While
      it may be a manifestation of brainstem pathology, this sign is often associated
      with conversion (somatisation) disorders and, if unrecognised as a sign of a
      psychogenic disorder, it may lead to unnecessary and occasionally invasive
      evaluation. METHODS: To better characterise this neuro-ophthalmologic sign, 36
      subjects were studied, 13 with psychogenic movement disorders, 11 with organic
      movement disorders and 12 normal controls. Patients were recorded during a
      manoeuvre to elicit convergence spasm and the videotapes were rated by two
      blinded raters on a scale of 0=normal, 1=mild convergence spasm and 2=marked
      convergence spasm. RESULTS: Convergence spasm was present in 9/13 (69%)
      psychogenic movement disorders cases, 4/11 (36%) non-psychogenic movement
      disorders cases and 4/12 (33%) controls (p=0.049 when psychogenic vs non
      psychogenic disorders or controls were compared). Inter-rater reliability
      analysis of the presence (rating 1 or 2) versus absence (rating 0) showed good
      agreement (27/36 or 75%; kappa 0.491, SE 0.141, p=0.002). Analysis for the
      presence of marked convergence spasm (rating 2) yielded agreement in 32/36
      (88.9%) examinations (kappa 0.652, SE 0.154, p<0.001) with a specificity of 87%
      (sensitivity 15%). CONCLUSION: Convergence spasm may provide benefit in the
      clinical examination of psychogenic movement disorders patients.

PMID- 21949108
TI  - The ghost in the machine: identifying mediators of intervention effectiveness.

PMID- 21949107
TI  - Screening patients with a family history of subarachnoid haemorrhage for
      intracranial aneurysms: screening uptake, patient characteristics and outcome.
AB  - BACKGROUND AND PURPOSE: People with one or more first degree relative affected
      (FDRA) by aneurysmal subarachnoid haemorrhage (aSAH) are at a higher lifetime
      risk of an aSAH than those without a family history. Screening may be worthwhile
      for people with two or more FDRA by aSAH. Little is known about the
      characteristics of people with a family history of aSAH who undergo screening in
      clinical practice. METHODS: Observational analysis of consecutive attendances at
      an intracranial aneurysm screening clinic. RESULTS: Of 96 adults seen, 19 did not
      have a family history of aSAH and 77 had one or more FDRA by aSAH: 35 had two or
      more FDRA, 21 had one FDRA plus one or more affected second degree relative and
      21 had one FDRA only. In these three respective groups, 29 (83%), 15 (71%) and
      five (24%) adults underwent screening, of whom six (21%), two (13%) and one (20%)
      had an aneurysm detected (p=0.5). Of the nine patients with aneurysms, four
      underwent treatment. Considering other risk factors, adults with two or more FDRA
      were more likely to be hypertensive (OR 3.3, 95% CI 1.0 to 10.8; p=0.046) but
      were no more likely to smoke or drink to excess than adults with one FDRA. Adults
      who underwent screening were more likely to be hypertensive and drink alcohol to
      excess (both p=0.03), but were no more likely to smoke than those who were not
      screened. CONCLUSIONS: In clinical practice, people undergoing intracranial
      aneurysm screening had stronger family histories of aSAH and they were also more
      likely to have modifiable risk factors for aSAH.

PMID- 21949109
TI  - Risk of squamous cell carcinoma of the skin in relation to IgE: a nested case
      control study.
AB  - BACKGROUND: Individuals diagnosed with nonmelanoma skin cancer have a high risk
      of developing a second skin cancer diagnosis. We assessed whether a marker of
      immune function related to atopic allergy, IgE, was associated with diagnosis of
      subsequent squamous cell carcinoma (SCC) of the skin in patients with a previous
      skin cancer enrolled in a skin cancer prevention trial. METHODS: One hundred
      twelve individuals who developed an SCC (cases) were compared with 227 controls
      who did not develop SCC over the same followup period, matched on age, sex, and
      study center. Total, respiratory, and food-specific IgE were measured in the
      baseline or year one (prior to diagnosis) sera samples for each subject. RESULTS:
      IgE levels were higher in cases with SCC than controls (comparing the highest
      quartile with the lowest, OR(total IgE) = 1.44; 95% CI: 0.73-2.85; OR(respiratory
      IgE) = 2.43; 95% CI: 1.16-5.06; OR(food IgE) = 2.53; 95% CI: 1.19-5.35). The
      association between respiratory IgE and subsequent skin cancer was strongest
      among individuals with a tendency to sunburn (OR(respiratory IgE) = 3.82; 95% CI:
      1.05-13.88) compared with those with a tendency to tan (OR(respiratory IgE) =
      0.95; 95% CI: 0.20-4.76). Among 25 subjects with repeat IgE measurements taken
      over several years, IgE levels were remarkably stable (interclass coefficient =
      0.90 for total IgE). CONCLUSION: These results indicate that allergy or allergy
      associated IgE may be indicative of an immune phenotype that enhances risk of
      SCC, possibly via immune-associate inflammatory mediators. IMPACT: Our results
      indicate that controlling allergy and IgE levels may be a new avenue of skin
      cancer prevention in susceptible populations, and implicate immune mechanisms in
      skin carcinogenesis.

PMID- 21949110
TI  - HPV and HPV vaccine education intervention: effects on parents, healthcare staff,
      and school staff.
AB  - BACKGROUND: Increasing knowledge about human papillomavirus (HPV) and HPV vaccine
      is a potentially important way to increase vaccination rates, yet few education
      interventions have addressed these topics. We report the results of an education
      intervention targeting three key groups who have contact with adolescent females.
      METHODS: We conducted HPV education intervention sessions during 2008 and 2009 in
      Guilford County, North Carolina. Parents (n = 376), healthcare staff (n = 118),
      and school staff (n = 456) attended the one-time sessions and completed self
      administered surveys. Analyses used mixed regression models to examine the
      intervention's effects on participants' self-rated HPV knowledge, objectively
      assessed HPV and HPV vaccine knowledge, and beliefs about HPV vaccine. RESULTS:
      Participants had relatively low levels of objectively assessed HPV and HPV
      vaccine knowledge prior to the intervention. The education intervention increased
      self-rated HPV knowledge among all three key groups (all P < 0.001), and
      objectively assessed knowledge about many aspects of HPV and HPV vaccine among
      healthcare and school staff members (all P < 0.05). Following the intervention,
      more than 90% of school staff members believed HPV and HPV vaccine education is
      worthwhile for school personnel and that middle schools are an appropriate venue
      for this education. Most parents (97%) and school staff members (85%) indicated
      they would be supportive of school-based vaccination clinics. CONCLUSIONS: Our
      education intervention greatly increased HPV and HPV vaccine knowledge among
      groups influential to the HPV vaccination behaviors of adolescent females.
      IMPACT: Education interventions represent a simple yet potentially effective
      strategy for increasing HPV vaccination and garnering stronger support for school
      based vaccination clinics.

PMID- 21949111
TI  - Platelet-activating factor stimulates sodium-hydrogen exchange in ventricular
      myocytes.
AB  - Sodium-hydrogen exchanger (NHE), the principal sarcolemmal acid extruder in
      ventricular myocytes, is stimulated by a variety of autocrine/paracrine factors
      and contributes to myocardial injury and arrhythmias during ischemia-reperfusion.
      Platelet-activating factor (PAF; 1-o-alkyl-2-acetyl-sn-glycero-3-phosphocholine)
      is a potent proinflammatory phospholipid that is released in the heart in
      response to oxidative stress and promotes myocardial ischemia-reperfusion injury.
      PAF stimulates NHE in neutrophils and platelets, but its effect on cardiac NHE
      (NHE1) is unresolved. We utilized quiescent guinea pig ventricular myocytes
      bathed in bicarbonate-free solutions and epifluorescence to measure intracellular
      pH (pH(i)). Methylcarbamyl-PAF (C-PAF; 200 nM), a metabolically stable analog of
      PAF, significantly increased steady-state pH(i). The alkalosis was completely
      blocked by the NHE inhibitor, cariporide, and by sodium-free bathing solutions,
      indicating it was mediated by NHE activation. C-PAF also significantly increased
      the rate of acid extrusion induced by intracellular acidosis. The ability of C
      PAF to increase steady-state pH(i) was completely blocked by the PAF receptor
      inhibitor WEB 2086 (10 MUM), indicating the PAF receptor is required. A MEK
      inhibitor (PD98059; 25 MUM) also completely blocked the rise in pH(i) induced by
      C-PAF, suggesting participation of the MAP kinase signaling cascade downstream of
      the PAF receptor. Inhibition of PKC with GF109203X (1 MUM) and chelerythrine (2
      MUM) did not significantly affect the alkalosis induced by C-PAF. In summary,
      these results provide evidence that PAF stimulates cardiac NHE1, the effect
      occurs via the PAF receptor, and signal relay requires participation of the MAP
      kinase cascade.

PMID- 21949112
TI  - Heterotrimeric Gi/Go proteins modulate endothelial TLR signaling independent of
      the MyD88-dependent pathway.
AB  - The innate immune recognition of bacterial lipopolysaccharide (LPS) is mediated
      by Toll-like receptor 4 (TLR4) and results in activation of proinflammatory
      signaling including NF-kappaB and MAPK pathways. Heterotrimeric G proteins have
      been previously implicated in LPS signaling in macrophages and monocytes. In the
      present study, we show that pertussis toxin sensitive heterotrimeric G proteins
      (Galpha(i/o)) are involved in the activation of MAPK and Akt downstream of TLR2,
      TLR3, and TLR4 in endothelial cells. Galpha(i/o) are also required for full
      activation of interferon signaling downstream of TLR3 and TLR4 but are not
      required for the activation of NF-kappaB. We find that Galpha(i/o)-mediated
      activation of the MAPK is independent of the canonical MyD88, interleukin-1
      receptor-associated kinase, and tumor necrosis factor receptor-associated factor
      6 signaling cascade in LPS-stimulated cells. Taken together, the data presented
      here suggest that heterotrimeric G proteins are widely involved in TLR pathways
      along a signaling cascade that is distinct from MyD88-TRAF6.

PMID- 21949113
TI  - ETA and ETB receptors are expressed in vascular adventitial fibroblasts.
AB  - The adventitia has been recognized to play important roles in vascular oxidative
      stress, remodeling, and contraction. We recently demonstrated that adventitial
      fibroblasts are able to express endothelin (ET)-1 in response to ANG II. However,
      it is unclear whether ET-1 receptors are expressed in the adventitia. We
      therefore investigated the expression and roles of both ET(A) and ET(B) receptors
      in collagen synthesis and ET-1 clearance in adventitial fibroblasts. Adventitial
      fibroblasts were isolated and cultured from the mouse thoracic aorta by the
      explant method. Cultured cells were treated with ANG II (100 nmol/l) or ET-1 (10
      pM) in the presence or absence of the ANG II type 1 receptor antagonist losartan
      (100 MUM), the ET-1 receptor antagonists BQ-123 (ET(A) receptor, 1 MUM) and BQ
      788 (ET(B) receptor, 1 MUM), and the ET(B) receptor agonist sarafotoxin 6C (100
      nM). ET-1 peptide levels were determined by ELISA, whereas ET(A), ET(B), and
      collagen levels were determined by Western blot analysis. ANG II increased ET-1
      peptide levels in a time-dependent manner. ANG II increased ET(A) and ET(B)
      receptor protein levels as well as collagen in a similar fashion. ANG II-induced
      collagen was reduced while in the presence of BQ-123, suggesting a role for the
      ET(A) receptor in the regulation of the extracellular matrix. ANG II treatment in
      the presence of BQ-788 significantly increased ET-1 peptide levels. Conversely,
      the ET(B) receptor agonist sarafotoxin 6C significantly decreased ET-1 peptide
      levels. These data implicate a role for the ET(B) receptor in the clearance of
      the ET-1 peptide. In conclusion, both ET(A) and ET(B) receptors are expressed in
      adventitial fibroblasts, which paves the ground for the biological significance
      of adventitial ET-1. The ET(A) receptor subtype mediates collagen I expression,
      whereas the ET(B) receptor subtype may play a protective role through increasing
      the clearance of the ET-1 peptide.

PMID- 21949114
TI  - Oxidative stress and heart failure.
AB  - Oxidative stress, defined as an excess production of reactive oxygen species
      (ROS) relative to antioxidant defense, has been shown to play an important role
      in the pathophysiology of cardiac remodeling and heart failure (HF). It induces
      subtle changes in intracellular pathways, redox signaling, at lower levels, but
      causes cellular dysfunction and damage at higher levels. ROS are derived from
      several intracellular sources, including mitochondria, NAD(P)H oxidase, xanthine
      oxidase, and uncoupled nitric oxide synthase. The production of ROS is increased
      within the mitochondria from failing hearts, whereas normal antioxidant enzyme
      activities are preserved. Chronic increases in ROS production in the mitochondria
      lead to a catastrophic cycle of mitochondrial DNA (mtDNA) damage as well as
      functional decline, further ROS generation, and cellular injury. ROS directly
      impair contractile function by modifying proteins central to excitation
      contraction coupling. Moreover, ROS activate a broad variety of hypertrophy
      signaling kinases and transcription factors and mediate apoptosis. They also
      stimulate cardiac fibroblast proliferation and activate the matrix
      metalloproteinases, leading to the extracellular matrix remodeling. These
      cellular events are involved in the development and progression of maladaptive
      myocardial remodeling and failure. Oxidative stress is also involved in the
      skeletal muscle dysfunction, which may be associated with exercise intolerance
      and insulin resistance in HF. Therefore, oxidative stress is involved in the
      pathophysiology of HF in the heart as well as in the skeletal muscle. A better
      understanding of these mechanisms may enable the development of novel and
      effective therapeutic strategies against HF.

PMID- 21949115
TI  - Effects of a reduction in the number of gap junction channels or in their
      conductance on ischemia-reperfusion arrhythmias in isolated mouse hearts.
AB  - A transient reduction of cell coupling during reperfusion limits myocardial
      necrosis, but little is known about its arrhythmogenic effects during ischemia
      reperfusion. Thus, we analyzed the effect of an extreme reduction in the number
      of gap junction channels or in their unitary conductance on ventricular
      arrhythmias during myocardial ischemia-reperfusion. Available gap junction
      uncouplers have electrophysiological effects independent from their uncoupling
      actions. Thus, isolated hearts from Cx43(Cre-ER(T)/fl) mice treated with 4
      hydroxytamoxifen (4-OHT), from Cx43KI32 mice [in which connexin (Cx)43 was
      replaced with Cx32], and from control animals were submitted to regional ischemia
      and reperfusion, and spontaneous and induced ventricular arrhythmias were
      monitored. In additional hearts, changes in activation time and electrical
      impedance during global ischemia-reperfusion were assessed. In contrast to
      treatment with 4-OHT, replacement of Cx43 with Cx32 did not modify baseline
      activation time or electrical impedance. However, the number of extrasistole and
      ventricular tachyarrhythmias was higher in isolated hearts from Cx43KI32 and 4
      OHT-treated Cx43(Cre-ER(T)/fl) animals versus wild-type animals during normoxia,
      ischemia (12.29 +/- 3.26 and 52.17 +/- 22.51 vs. 3.00 +/- 1.46 spontaneous
      tachyarrhythmias, P < 0.05), and reperfusion. The impairment in conduction during
      ischemia was steeper in isolated hearts from Cx43KI32 animals, whereas changes in
      myocardial impedance were attenuated during ischemia in both transgenic models,
      suggesting altered cell-to-cell coupling at baseline. In conclusion, both
      reduction of Cx43 with 4-OHT and replacement of Cx43 by less-conductive Cx32 were
      arrhythmogenic under normoxia and ischemia-reperfusion, despite no major effects
      on baseline electrical properties. These results suggest that modifications in
      gap junction communication silent under normal conditions may be arrhythmogenic
      during ischemia-reperfusion.

PMID- 21949116
TI  - Left-ventricular shape determines intramyocardial mechanical heterogeneity.
AB  - Left-ventricular remodeling is considered to be an important mechanism of disease
      progression leading to mechanical dysfunction of the heart. However, the
      interaction between the physiological changes in the remodeling process and the
      associated mechanical dysfunction is still poorly understood. Clinically, it has
      been observed that the left ventricle often undergoes large shape changes, but
      the importance of left-ventricular shape as a contributing factor to alterations
      in mechanical function has not been clearly determined. Therefore, the
      interaction between left-ventricular shape and systolic mechanical function was
      examined in a computational finite-element study. Hereto, finite-element models
      were constructed with varying shapes, ranging from an elongated ellipsoid to a
      sphere. A realistic transmural gradient in fiber orientation was considered. The
      passive myocardium was described by an incompressible hyperelastic material law
      with transverse isotropic symmetry. Activation was governed by the eikonal
      diffusion equation. Contraction was incorporated using a Hill model. For each
      shape, simulations were performed in which passive filling was followed by
      isovolumic contraction and ejection. It was found that the intramyocardial
      distributions of fiber stress, strain, and stroke work density were shape
      dependent. Ejection performance was reduced with increasing sphericity, which was
      regionally related to a reduction in the active fiber stress development, fiber
      shortening, and stroke work in the midwall and subepicardial region at the
      midheight level in the left-ventricular wall. Based on these results, we conclude
      that a significant interaction exists between left-ventricular shape and regional
      myofiber mechanics, but the importance for left-ventricular remodeling requires
      further investigation.

PMID- 21949117
TI  - Contributions of A2A and A2B adenosine receptors in coronary flow responses in
      relation to the KATP channel using A2B and A2A/2B double-knockout mice.
AB  - Adenosine plays a role in physiological and pathological conditions, and A(2)
      adenosine receptor (AR) expression is modified in many cardiovascular disorders.
      In this study, we elucidated the role of the A(2B)AR and its relationship to the
      A(2A)AR in coronary flow (CF) changes using A(2B) single-knockout (KO) and
      A(2A/2B) double-KO (DKO) mice in a Langendorff setup. We used two approaches: 1)
      selective and nonselective AR agonists and antagonists and 2) A(2A)KO and A(2B)KO
      and A(2A/2B)DKO mice. BAY 60-6583 (a selective A(2B) agonist) had no effect on CF
      in A(2B)KO mice, whereas it significantly increased CF in wild-type (WT) mice
      (maximum of 23.3 +/- 9 ml.min(-1).g(-1)). 5'-N-ethylcarboxamido adenosine (NECA;
      a nonselective AR agonist) increased CF in A(2B)KO mice (maximum of 34.6 +/- 4.7
      ml.min(-1).g(-1)) to a significantly higher degree compared with WT mice (maximum
      of 23.1 +/- 2.1 ml.min(-1).g(-1)). Also, CGS-21680 (a selective A(2A) agonist)
      increased CF in A(2B)KO mice (maximum of 29 +/- 1.9 ml.min(-1).g(-1)) to a
      significantly higher degree compared with WT mice (maximum of 25.1 +/- 2.3
      ml.min(-1).g(-1)). SCH-58261 (an A(2A)-selective antagonist) inhibited the NECA
      induced increase in CF to a significantly higher degree in A(2B)KO mice (19.3 +/-
      1.6 vs. 0.5 +/- 0.4 ml.min(-1).g(-1)) compared with WT mice (19 +/- 3.5 vs. 3.6
      +/- 0.5 ml.min(-1).g(-1)). NECA did not induce any increase in CF in A(2A/2B)DKO
      mice, whereas a significant increase was observed in WT mice (maximum of 23.1 +/-
      2.1 ml.min(-1).g(-1)). Furthermore, the mitochondrial ATP-sensitive K(+) (K(ATP))
      channel blocker 5-hydroxydecanoate had no effect on the NECA-induced increase in
      CF in WT mice, whereas the NECA-induced increase in CF in WT (17.6 +/- 2 ml.min(
      1).g(-1)), A(2A)KO (12.5 +/- 2.3 ml.min(-1).g(-1)), and A(2B)KO (16.2 +/- 0.8
      ml.min(-1).g(-1)) mice was significantly blunted by the K(ATP) channel blocker
      glibenclamide (to 0.7 +/- 0.7, 2.3 +/- 1.1, and 0.9 +/- 0.4 ml.min(-1).g(-1),
      respectively). Also, the CGS-21680-induced (22 +/- 2.3 ml.min(-1).g(-1)) and BAY
      60-6583-induced (16.4 +/- 1.60 ml.min(-1).g(-1)) increase in CF in WT mice was
      significantly blunted by glibenclamide (to 1.2 +/- 0.4 and 1.8 +/- 1.2 ml.min(
      1).g(-1), respectively). In conclusion, this is the first evidence supporting the
      compensatory upregulation of A(2A)ARs in A(2B)KO mice and demonstrates that both
      A(2A)ARs and A(2B)ARs induce CF changes through K(ATP) channels. These results
      identify AR-mediated CF responses that may lead to better therapeutic approaches
      for the treatment of cardiovascular disorders.

PMID- 21949118
TI  - Proteasome functional insufficiency in cardiac pathogenesis.
AB  - The ubiquitin-proteasome system (UPS) is responsible for the degradation of most
      cellular proteins. Alterations in cardiac UPS, including changes in the
      degradation of regulatory proteins and proteasome functional insufficiency, are
      observed in many forms of heart disease and have been shown to play an important
      role in cardiac pathogenesis. In the past several years, remarkable progress in
      understanding the mechanisms that regulate UPS-mediated protein degradation has
      been achieved. A transgenic mouse model of benign enhancement of cardiac
      proteasome proteolytic function has been created. This has led to the first
      demonstration of the necessity of proteasome functional insufficiency in the
      genesis of important pathological processes. Cardiomyocyte-restricted enhancement
      of proteasome proteolytic function by overexpression of proteasome activator
      28alpha protects against cardiac proteinopathy and myocardial ischemia
      reperfusion injury. Additionally, exciting advances have recently been achieved
      in the search for a pharmacological agent to activate the proteasome. These
      breakthroughs are expected to serve as an impetus to further investigation into
      the involvement of UPS dysfunction in molecular pathogenesis and to the
      development of new therapeutic strategies for combating heart disease. An
      interplay between the UPS and macroautophagy is increasingly suggested in
      noncardiac systems but is not well understood in the cardiac system. Further
      investigations into the interplay are expected to provide a more comprehensive
      picture of cardiac protein quality control and degradation.

PMID- 21949119
TI  - A glycosphingolipid/caveolin-1 signaling complex inhibits motility of human
      ovarian carcinoma cells.
AB  - The genetic (stable overexpression of sialyltransferase I, GM3 synthase) or
      pharmacological (selective pressure by N-(4-hydroxyphenyl)retinamide))
      manipulation of A2780 human ovarian cancer cells allowed us to obtain clones
      characterized by higher GM3 synthase activity compared with wild-type cells.
      Clones with high GM3 synthase expression had elevated ganglioside levels, reduced
      in vitro cell motility, and enhanced expression of the membrane adaptor protein
      caveolin-1 with respect to wild-type cells. In high GM3 synthase-expressing
      clones, both depletion of gangliosides by treatment with the glucosylceramide
      synthase inhibitor D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol and
      silencing of caveolin-1 by siRNA were able to strongly increase in vitro cell
      motility. The motility of wild-type, low GM3 synthase-expressing cells was
      reduced in the presence of a Src inhibitor, and treatment of these cells with
      exogenous gangliosides, able to reduce their in vitro motility, inactivated c-Src
      kinase. Conversely, ganglioside depletion by D-threo-1-phenyl-2-decanoylamino-3
      morpholino-1-propanol treatment or caveolin-1 silencing in high GM3 synthase
      expressing cells led to c-Src kinase activation. In high GM3 synthase-expressing
      cells, caveolin-1 was associated with sphingolipids, integrin receptor subunits,
      p130(CAS), and c-Src forming a Triton X-100-insoluble noncaveolar signaling
      complex. These data suggest a role for gangliosides in regulating tumor cell
      motility by affecting the function of a signaling complex organized by caveolin
      1, responsible for Src inactivation downstream to integrin receptors, and imply
      that GM3 synthase is a key target for the regulation of cell motility in human
      ovarian carcinoma.

PMID- 21949120
TI  - Inactivation of glycogen synthase kinase-3beta is required for osteoclast
      differentiation.
AB  - Glycogen synthase kinase-3beta (GSK-3beta) is a serine/threonine kinase
      originally identified as a regulator of glycogen deposition. Although the role of
      GSK-3beta in osteoblasts is well characterized as a negative regulator of beta
      catenin, its effect on osteoclast formation remains largely unidentified. Here,
      we show that the GSK-3beta inactivation upon receptor activator of NF-kappaB
      ligand (RANKL) stimulation is crucial for osteoclast differentiation. Regulation
      of GSK-3beta activity in bone marrow macrophages by retroviral expression of the
      constitutively active GSK-3beta (GSK3beta-S9A) mutant inhibits RANKL-induced
      osteoclastogenesis, whereas expression of the catalytically inactive GSK-3beta
      (GSK3beta-K85R) or small interfering RNA (siRNA)-mediated GSK-3beta silencing
      enhances osteoclast formation. Pharmacological inhibition of GSK-3beta further
      confirmed the negative role of GSK-3beta in osteoclast formation. We also show
      that overexpression of the GSK3beta-S9A mutant in bone marrow macrophages
      inhibits RANKL-mediated NFATc1 induction and Ca(2+) oscillations. Remarkably,
      transgenic mice expressing the GSK3beta-S9A mutant show an osteopetrotic
      phenotype due to impaired osteoclast differentiation. Further, osteoclast
      precursor cells from the transgenic mice show defects in expression and nuclear
      localization of NFATc1. These findings demonstrate a novel role for GSK-3beta in
      the regulation of bone remodeling through modulation of NFATc1 in RANKL
      signaling.

PMID- 21949121
TI  - Inhibition of mTOR kinase by AZD8055 can antagonize chemotherapy-induced cell
      death through autophagy induction and down-regulation of p62/sequestosome 1.
AB  - AZD8055 is an ATP-competitive inhibitor of mammalian target of rapamycin (mTOR)
      that forms two multiprotein complexes, mTORC1 and mTORC2, and negatively
      regulates autophagy. We demonstrate that AZD8055 stimulates and potentiates
      chemotherapy-mediated autophagy, as shown by LC3I-II conversion and down
      regulation of the ubiquitin-binding protein p62/sequestosome 1. AZD8055-induced
      autophagy was pro-survival as shown by its ability to attenuate cell death and
      DNA damage (p-H2AX), and to enhance clonogenic survival by cytotoxic
      chemotherapy. Autophagy inhibition by siRNA against Beclin 1 or LC3B, or by
      chloroquine, partially reversed the cytoprotective effect of AZD8055 that was
      independent of cell cycle inhibition. The pro-survival role of autophagy was
      confirmed using ectopic expression of Beclin 1 that conferred cytoprotection. To
      determine whether autophagy-mediated down-regulation of p62/sequestosome 1
      contributes to its pro-survival role, we generated p62 knockdown cells using
      shRNA that showed protection from chemotherapy-induced cell death and DNA damage.
      We also overexpressed wild-type (wt) p62 that promoted chemotherapy-induced cell
      death, whereas mutated p62 at functional domains (PB1, UBA) failed to do so. The
      ability of ectopic wt p62 to promote cell death was blocked by AZD8055. AZD8055
      was shown to inhibit phosphorylation of the autophagy-initiating kinase ULK1 at
      Ser(757) and inhibited known targets of mTORC1 (p-mTOR Ser(2448), p70S6K, p-S6,
      p4EBP1) and mTORC2 (p-mTOR Ser(2481), p-AKT Ser(473)). Knockdown of mTOR, but not
      Raptor or Rictor, reduced p-ULK1 at Ser(757) and enhanced chemotherapy-induced
      autophagy that resulted in a similar cytoprotective effect as shown for AZD8055.
      In conclusion, AZD8055 inhibits mTOR kinase and ULK1 phosphorylation to induce
      autophagy whose pro-survival effect is due, in part, to down-regulation of p62.

PMID- 21949122
TI  - Gle1 is a multifunctional DEAD-box protein regulator that modulates Ded1 in
      translation initiation.
AB  - DEAD-box protein (Dbp) family members are essential for gene expression; however,
      their precise roles and regulation are not fully defined. During messenger (m)RNA
      export, Gle1 bound to inositol hexakisphosphate (IP(6)) acts via Dbp5 to
      facilitate remodeling of mRNA-protein complexes. In contrast, here we define a
      novel Gle1 role in translation initiation through regulation of a different DEAD
      box protein, the initiation factor Ded1. We find that Gle1 physically and
      genetically interacts with Ded1. Surprisingly, whereas Gle1 stimulates Dbp5, it
      inhibits Ded1 ATPase activity in vitro, and IP(6) does not affect this
      inhibition. Functionally, a gle1-4 mutant specifically suppresses initiation
      defects in a ded1-120 mutant, and ded1 and gle1 mutants have complementary
      perturbations in AUG start site recognition. Consistent with this role in
      initiation, Gle1 inhibits translation in vitro in competent extracts. These
      results indicate that Gle1 has a direct role in initiation and negatively
      regulates Ded1. Together, the differential regulation of two distinct DEAD-box
      proteins by a common factor (Gle1) establishes a new paradigm for controlling
      gene expression and coupling translation with mRNA export.

PMID- 21949123
TI  - Different signaling pathways stimulate a disintegrin and metalloprotease-17
      (ADAM17) in neutrophils during apoptosis and activation.
AB  - ADAM17 is a membrane-associated metalloprotease that cleaves proteins from the
      surface of neutrophils and modulates the density of various receptors and
      adhesion molecules. The protease activity of ADAM17 is highly inducible and
      occurs upon neutrophil activation as well as apoptosis. At this time, little is
      known about the signal transduction pathway that promotes ADAM17 activity in
      neutrophils upon the induction of apoptosis. We show that caspase-8 activation,
      Bid cleavage, and the release of mitochondrial reactive oxygen species are
      sequential transduction components of the Fas signaling cascade that induces
      ADAM17. This is different from ADAM17 stimulation upon overt neutrophil
      activation, which requires MAPK p38 or ERK, but not caspases and reactive oxygen
      species. ADAM17 activity in apoptotic neutrophils may serve to inactivate select
      effector molecules that promote the pro-inflammatory activity of recruited
      neutrophils. For instance, TNFalpha receptors TNF-RI and TNF-RII are substrates
      of ADAM17, and we show that they are shed during apoptosis, decreasing neutrophil
      sensitivity to TNFalpha. Altogether, our findings provide significant new
      insights into the signal transduction pathway that stimulates ADAM17 during
      induced neutrophil apoptosis. ADAM17 induction during apoptosis may rapidly
      diminish neutrophil sensitivity to the inflammatory environment, complementing
      other anti-inflammatory activities by these cells during inflammation resolution.

PMID- 21949124
TI  - Proteolytic cleavage of chemerin protein is necessary for activation to the
      active form, Chem157S, which functions as a signaling molecule in glioblastoma.
AB  - Chemerin is a chemoattractant involved in innate and adaptive immunity as well as
      an adipokine implicated in adipocyte differentiation. Chemerin circulates as an
      inactive precursor in blood whose bioactivity is closely regulated through
      proteolytic processing at its C terminus. We developed methodology for production
      of different recombinant chemerin isoforms (chem163S, chem157S, and chem155A)
      which allowed us to obtain large quantities of these proteins with purity of
      >95%. Chem158K was generated from chem163S by plasmin cleavage. Characterization
      by mass spectrometry and Edman degradation demonstrated that both the N and C
      termini were correct for each isoform. Ca(2+) mobilization assays showed that the
      EC(50) values for chem163S and chem158K were 54.2 +/- 19.9 nm and 65.2 +/- 13.2
      nm, respectively, whereas chem157S had a ~50-fold higher potency with an EC(50)
      of 1.2 +/- 0.7 nm. Chem155A had no agonist activity and weak antagonist activity,
      causing a 50% reduction of chem157S activity at a molar ratio of 100:1. Similar
      results were obtained in a chemotaxis assay. Because chem158K is the dominant
      form in cerebrospinal fluid from patients with glioblastoma (GBM), we examined
      the significance of chemerin in GBM biology. In silico analysis showed chemerin
      mRNA was significantly increased in tissue from grade III and IV gliomas.
      Furthermore, U-87 MG cells, a human GBM line, express the chemerin receptors,
      chemokine-like receptor 1 and chemokine receptor-like 2, and chem157S triggered
      Ca(2+) flux. This study emphasized the necessity of appropriate C-terminal
      proteolytic processing to generate the likely physiologic form of active
      chemerin, chem157S, and suggested a possible role in malignant GBM.

PMID- 21949125
TI  - Trypanosoma brucei metacaspase 4 is a pseudopeptidase and a virulence factor.
AB  - Metacaspases are caspase family cysteine peptidases found in plants, fungi, and
      protozoa but not mammals. Trypanosoma brucei is unusual in having five
      metacaspases (MCA1-MCA5), of which MCA1 and MCA4 have active site substitutions,
      making them possible non-enzymatic homologues. Here we demonstrate that
      recombinant MCA4 lacks detectable peptidase activity despite maintaining a
      functional peptidase structure. MCA4 is expressed primarily in the bloodstream
      form of the parasite and associates with the flagellar membrane via dual
      myristoylation/palmitoylation. Loss of function phenotyping revealed critical
      roles for MCA4; rapid depletion by RNAi caused lethal disruption to the
      parasite's cell cycle, yet the generation of MCA4 null mutant parasites
      (Deltamca4) was possible. Deltamca4 had normal growth in axenic culture but
      markedly reduced virulence in mice. Further analysis revealed that MCA4 is
      released from the parasite and is specifically processed by MCA3, the only
      metacaspase that is both palmitoylated and enzymatically active. Accordingly, we
      have identified that the multiple metacaspases in T. brucei form a membrane
      associated proteolytic cascade to generate a pseudopeptidase virulence factor.

PMID- 21949126
TI  - Glycolytic and non-glycolytic functions of Mycobacterium tuberculosis fructose
      1,6-bisphosphate aldolase, an essential enzyme produced by replicating and non
      replicating bacilli.
AB  - The search for antituberculosis drugs active against persistent bacilli has led
      to our interest in metallodependent class II fructose-1,6-bisphosphate aldolase
      (FBA-tb), a key enzyme of gluconeogenesis absent from mammalian cells. Knock-out
      experiments at the fba-tb locus indicated that this gene is required for the
      growth of Mycobacterium tuberculosis on gluconeogenetic substrates and in glucose
      containing medium. Surface labeling and enzymatic activity measurements revealed
      that this enzyme was exported to the cell surface of M. tuberculosis and produced
      under various axenic growth conditions including oxygen depletion and hence by
      non-replicating bacilli. Importantly, FBA-tb was also produced in vivo in the
      lungs of infected guinea pigs and mice. FBA-tb bound human plasmin(ogen) and
      protected FBA-tb-bound plasmin from regulation by alpha(2)-antiplasmin,
      suggestive of an involvement of this enzyme in host/pathogen interactions. The
      crystal structures of FBA-tb in the native form and in complex with a hydroxamate
      substrate analog were determined to 2.35- and 1.9-A resolution, respectively.
      Whereas inhibitor attachment had no effect on the plasminogen binding activity of
      FBA-tb, it competed with the natural substrate of the enzyme, fructose 1,6
      bisphosphate, and substantiated a previously unknown reaction mechanism
      associated with metallodependent aldolases involving recruitment of the catalytic
      zinc ion by the substrate upon active site binding. Altogether, our results
      highlight the potential of FBA-tb as a novel therapeutic target against both
      replicating and non-replicating bacilli.

PMID- 21949127
TI  - p21-Activated kinase 3 (PAK3) protein regulates synaptic transmission through its
      interaction with the Nck2/Grb4 protein adaptor.
AB  - Mutations in the p21-activated kinase 3 gene (pak3) are responsible for
      nonsyndromic forms of mental retardation. Expression of mutated PAK3 proteins in
      hippocampal neurons induces abnormal dendritic spine morphology and long term
      potentiation anomalies, whereas pak3 gene invalidation leads to cognitive
      impairments. How PAK3 regulates synaptic plasticity is still largely unknown. To
      better understand how PAK3 affects neuronal synaptic plasticity, we focused on
      its interaction with the Nck adaptors that play a crucial role in PAK signaling.
      We report here that PAK3 interacts preferentially with Nck2/Grb4 in brain
      extracts and in transfected cells. This interaction is independent of PAK3 kinase
      activity. Selective uncoupling of the Nck2 interactions in acute cortical slices
      using an interfering peptide leads to a rapid increase in evoked transmission to
      pyramidal neurons. The P12A mutation in the PAK3 protein strongly decreases the
      interaction with Nck2 but only slightly with Nck1. In transfected hippocampal
      cultures, expression of the P12A-mutated protein has no effect on spine
      morphogenesis or synaptic density. The PAK3-P12A mutant does not affect synaptic
      transmission, whereas the expression of the wild-type PAK3 protein decreases the
      amplitude of spontaneous miniature excitatory currents. Altogether, these data
      show that PAK3 down-regulates synaptic transmission through its interaction with
      Nck2.

PMID- 21949128
TI  - A novel NADH-dependent and FAD-containing hydroxylase is crucial for nicotine
      degradation by Pseudomonas putida.
AB  - Nicotine, the main alkaloid produced by Nicotiana tabacum and other Solanaceae,
      is very toxic and may be a leading toxicant causing preventable disease and
      death, with the rise in global tobacco consumption. Several different microbial
      pathways of nicotine metabolism have been reported: Arthrobacter uses the
      pyridine pathway, and Pseudomonas, like mammals, uses the pyrrolidine pathway. We
      identified and characterized a novel 6-hydroxy-3-succinoyl-pyridine (HSP)
      hydroxylase (HspB) using enzyme purification, peptide sequencing, and sequencing
      of the Pseudomonas putida S16 genome. The HSP hydroxylase has no known orthologs
      and converts HSP to 2,5-dihydroxy-pyridine and succinic semialdehyde, using NADH.
      (18)O(2) labeling experiments provided direct evidence for the incorporation of
      oxygen from O(2) into 2,5-dihydroxy-pyridine. The hspB gene deletion showed that
      this enzyme is essential for nicotine degradation, and site-directed mutagenesis
      identified an FAD-binding domain. This study demonstrates the importance of the
      newly discovered enzyme HspB, which is crucial for nicotine degradation by the
      Pseudomonas strain.

PMID- 21949129
TI  - Revisitation of the betaCl-elimination reaction of D-amino acid oxidase: new
      interpretation of the reaction that sparked flavoprotein dehydrogenation
      mechanisms.
AB  - D-amino acid oxidase (DAAO) from pig has been reported to catalyze the beta
      elimination of Cl(-) from betaCl-D-alanine via abstraction of the substrate alpha
      H as H(+) ("carbanion mechanism") (Walsh, C. T., Schonbrunn, A., and Abeles, R.
      H. (1971) J. Biol. Chem. 246, 6855-6866). In view of the fundamental mechanistic
      importance of this reaction and of the recent reinterpretation of the DAAO
      dehydrogenation step as occurring via a hydride mechanism, we reinvestigated the
      elimination reaction using yeast DAAO. That enzyme catalyzes the same reactions
      as the pig enzyme but with a much higher efficiency and a substantially different
      kinetic behavior. The reaction is initiated by a very rapid and fully reversible
      dehydrogenation step. This leads to an equilibrium (k(on) ~ k(reverse)) between
      the complexes of oxidized enzyme-betaCl-D-alanine and reduced enzyme-betaCl
      iminopyruvate. In the presence of O(2) the latter complex can partition between
      an oxidative half-reaction and elimination of Cl(-), which proceeds at a rate of
      ~50 s(-1). This step forms a complex between oxidized enzyme and enamine that is
      characterized by a charge transfer absorption (which describes its rates of
      formation and decay). A minimal scheme that lists relevant steps of the reductive
      and oxidative half-reactions and elimination pathways along with the estimate of
      the corresponding rate constants is presented. beta-Elimination of Cl(-) is
      proposed to originate at the locus of the enzyme-betaCl-iminopyruvate complex. A
      chemical mechanism that can account for elimination is discussed in detail.

PMID- 21949130
TI  - CD105 protein depletion enhances human adipose-derived stromal cell osteogenesis
      through reduction of transforming growth factor beta1 (TGF-beta1) signaling.
AB  - Clinically available sources of bone for repair and reconstruction are limited by
      the accessibility of autologous grafts, infectious risks of cadaveric materials,
      and durability of synthetic substitutes. Cell-based approaches for skeletal
      regeneration can potentially fill this need, and adipose tissue represents a
      promising source for development of such therapies. Here, we enriched for an
      osteogenic subpopulation of cells derived from human subcutaneous adipose tissue
      utilizing microfluidic-based single cell transcriptional analysis and
      fluorescence-activated cell sorting (FACS). Statistical analysis of single cell
      transcriptional profiles demonstrated that low expression of endoglin (CD105)
      correlated with a subgroup of adipose-derived cells with increased osteogenic
      gene expression. FACS-sorted CD105(low) cells demonstrated significantly enhanced
      in vitro osteogenic differentiation and in vivo bone regeneration when compared
      with either CD105(high) or unsorted cells. Evaluation of the endoglin pathway
      suggested that enhanced osteogenesis among CD105(low) adipose-derived cells is
      likely due to identification of a subpopulation with lower TGF-beta1/Smad2
      signaling. These findings thus highlight a potential avenue to promote
      osteogenesis in adipose-derived mesenchymal cells for skeletal regeneration.

PMID- 21949131
TI  - Fibronectin aggregation and assembly: the unfolding of the second fibronectin
      type III domain.
AB  - The mechanism of fibronectin (FN) assembly and the self-association sites are
      still unclear and contradictory, although the N-terminal 70-kDa region ((I)1-9)
      is commonly accepted as one of the assembly sites. We previously found that (I)1
      9 binds to superfibronectin, which is an artificial FN aggregate induced by
      anastellin. In the present study, we found that (I)1-9 bound to the aggregate
      formed by anastellin and a small FN fragment, (III)1-2. An engineered disulfide
      bond in (III)2, which stabilizes folding, inhibited aggregation, but a disulfide
      bond in (III)1 did not. A gelatin precipitation assay showed that (I)1-9 did not
      interact with anastellin, (III)1, (III)2, (III)1-2, or several (III)1-2 mutants
      including (III)1-2KADA. (In contrast to previous studies, we found that the
      (III)1-2KADA mutant was identical in conformation to wild-type (III)1-2.) Because
      (I)1-9 only bound to the aggregate and the unfolding of (III)2 played a role in
      aggregation, we generated a (III)2 domain that was destabilized by deletion of
      the G strand. This mutant bound (I)1-9 as shown by the gelatin precipitation
      assay and fluorescence resonance energy transfer analysis, and it inhibited FN
      matrix assembly when added to cell culture. Next, we introduced disulfide
      mutations into full-length FN. Three disulfide locks in (III)2, (III)3, and
      (III)11 were required to dramatically reduce anastellin-induced aggregation. When
      we tested the disulfide mutants in cell culture, only the disulfide bond in
      (III)2 reduced the FN matrix. These results suggest that the unfolding of (III)2
      is one of the key factors for FN aggregation and assembly.

PMID- 21949132
TI  - TNF-alpha and IL-1beta promote a disintegrin-like and metalloprotease with
      thrombospondin type I motif-5-mediated aggrecan degradation through syndecan-4 in
      intervertebral disc.
AB  - Elevated levels of TNF-alpha, IL-1beta and a resultant increase in ADAMTS (a
      disintegrin-like and metalloprotease with thrombospondin type I motifs)
      expression is seen during disc degeneration. However, if these pro-inflammatory
      cytokines control ADAMTS activity is not definitively known. The goal of the
      investigation was to study if TNF-alpha and IL-1beta regulate syndecan-4 (SDC4)
      expression, and if SDC4 was responsible for promoting aggrecan degradation
      through controlling ADAMTS activity in nucleus pulposus cells of the
      intervertebral disc. Cytokine treatment increased SDC4 expression and promoter
      activity. Use of inhibitor, SM7368 and co-transfections with IkappaBalpha,
      RelA/p50 showed that NF-kappaBeta regulated both basal and cytokine-dependent
      SDC4 transcription. SDC4 promoter harboring RelA binding site mutation was
      unresponsive to the cytokines. Moreover, cytokines failed to increase SDC4
      promoter activity in RelA-null cells. Cytokines increased ADAMTS-4/5 expression
      and aggrecan degradation and promoted SDC4 interaction with ADAMTS-5. Treatment
      with heparinase-III and p-nitrophenyl-beta-D-xylopyranoside (PNPX), an inhibitor
      of heparan sulfate synthesis and transfection with SDC4-shRNA partially blocked
      cytokine mediated aggrecan degradation. Analysis of human tissues showed
      increased aggrecan degradation with a concomitant increase in SDC4 and ADAMTS-5
      protein expression with severity of disc disease. Likewise, SDC4, TNF-alpha, IL
      1beta, ADAMTS-4, and ADAMTS-5 mRNA expression increased in degenerate tissues. We
      conclude that in nucleus pulposus, TNF-alpha and IL-1beta regulate SDC4
      expression, which plays a key role in pathogenesis of degenerative disc disease
      by promoting aggrecan degradation by ADAMTS-5.

PMID- 21949133
TI  - In vitro and in vivo anticancer activity of a synthetic glycolipid as Toll-like
      receptor 4 (TLR4) activator.
AB  - Activation of Toll-like receptor 4 (TLR4) triggers the innate immune response and
      leads to the induction of adaptive immunity. TLR4 agonists are known to function
      as immunostimulants and exhibit promising therapeutic potential for cancer
      immunotherapy. We have previously developed a synthetic serine-based glycolipid
      (designated as CCL-34) that can activate TLR4-dependent signaling pathways. In
      this study, the anticancer immunity of CCL-34 was further demonstrated. CCL-34
      activated macrophages induced cancer cell death via the apoptotic pathway, and
      this cytotoxicity was significantly inhibited by NG-monomethyl-L-arginine (an
      inducible NOS inhibitor). Notably, conditioned medium collected from CCL-34
      treated splenocytes also induced cytotoxicity toward cancer cells. Furthermore,
      CCL-34 treatment suppressed tumor growth and increased the survival rate in TLR4
      functional C3H/HeN mice but not in TLR4-defective C3H/HeJ mice. Increased
      apoptosis, the induction of cytokines (IFN-gamma and IL-12) and chemokines (CXCL9
      and CXCL10), and the elevation of leukocyte markers (CD11b, CD11c, CD4, and CD8)
      were detected at tumor sites in C3H/HeN mice but not in C3H/HeJ mice. Structure
      and-activity relationship analysis of CCL-34 and its structural analogs revealed
      that a sugar moiety is essential for its activity. However, the substitution of
      the galactose in CCL-34 with glucose or fucose did not reduce its activity.
      Altogether, this study reveals the anticancer activity of a new synthetic TLR4
      agonist and broadens the molecular basis of TLR4-activating glycolipids.

PMID- 21949134
TI  - Down-regulation of UDP-glucuronic acid biosynthesis leads to swollen plant cell
      walls and severe developmental defects associated with changes in pectic
      polysaccharides.
AB  - UDP-glucose dehydrogenase (UGD) plays a key role in the nucleotide sugar
      biosynthetic pathway, as its product UDP-glucuronic acid is the common precursor
      for arabinose, xylose, galacturonic acid, and apiose residues found in the cell
      wall. In this study we characterize an Arabidopsis thaliana double mutant ugd2,3
      that lacks two of the four UGD isoforms. This mutant was obtained from a cross of
      ugd2 and ugd3 single mutants, which do not show phenotypical differences compared
      with the WT. In contrast, ugd2,3 has a strong dwarfed phenotype and often
      develops seedlings with severe root defects suggesting that the UGD2 and UGD3
      isoforms act in concert. Differences in its cell wall composition in comparison
      to the WT were determined using biochemical methods indicating a significant
      reduction in arabinose, xylose, apiose, and galacturonic acid residues.
      Xyloglucan is less substituted with xylose, and pectins have a reduced amount of
      arabinan side chains. In particular, the amount of the apiose containing side
      chains A and B of rhamnogalacturonan II is strongly reduced, resulting in a
      swollen cell wall. The alternative pathway to UDP-glucuronic acid with the key
      enzyme myo-inositol oxygenase is not up-regulated in ugd2,3. The pathway also
      does not complement the ugd2,3 mutation, likely because the supply of myo
      inositol is limited. Taken together, the presented data underline the importance
      of UDP GlcA for plant primary cell wall formation.

PMID- 21949135
TI  - Infant growth before and after term: effects on neurodevelopment in preterm
      infants.
AB  - OBJECTIVE: To identify sensitive periods of postnatal growth for preterm infants
      relative to neurodevelopment at 18 months' corrected age. PATIENTS AND METHODS:
      We studied 613 infants born at <33 weeks' gestation who participated in the DHA
      for Improvement of Neurodevelopmental Outcome trial. We calculated linear slopes
      of growth in weight, length, BMI, and head circumference from 1 week of age to
      term (40 weeks' postmenstrual age), term to 4 months, and 4 to 12 months, and we
      estimated their associations with Bayley Scales of Infant Development, 2nd
      Edition, Mental (MDI) and Psychomotor (PDI) Development Indexes in linear
      regression. RESULTS: The median gestational age was 30 (range: 2-33) weeks. Mean
      +/- SD MDI was 94 +/- 16, and PDI was 93 +/- 16. From 1 week to term, greater
      weight gain (2.4 MDI points per z score [95% confidence interval (CI): 0.8-3.9];
      2.7 PDI points [95% CI: 1.2-.2]), BMI gain (1.7 MDI points [95% CI: 0.4-3.1]; 2.5
      PDI points [95% CI: 1.2-3.9]), and head growth (1.4 MDI points [95% CI: -0.0
      2.8]; 2.5 PDI points [95% CI: 1.2-3.9]) were associated with higher scores. From
      term to 4 months, greater weight gain (1.7 points [95% CI: 0.2-3.1]) and linear
      growth (2.0 points [95% CI: 0.7-3.2]), but not BMI gain, were associated with
      higher PDI. From 4 to 12 months, none of the growth measures was associated with
      MDI or PDI score. CONCLUSIONS: In preterm infants, greater weight and BMI gain to
      term were associated with better neurodevelopmental outcomes. After term, greater
      weight gain was also associated with better outcomes, but increasing weight out
      of proportion to length did not confer additional benefit.

PMID- 21949136
TI  - Recommendations for administering hepatitis A vaccine to contacts of
      international adoptees.
AB  - The Advisory Committee on Immunization Practices of the Centers for Disease
      Control and Prevention and the American Academy of Pediatrics (AAP) recommend
      routine administration of hepatitis A vaccine for household members and close
      contacts, including baby-sitters, when children are adopted from countries with
      high or intermediate rates of hepatitis A infection. This policy expands previous
      AAP recommendations to immunize travelers to countries who are seeking to adopt a
      child in countries with high or medium hepatitis A endemicity. All previously
      nonimmune unvaccinated people who anticipate close exposure to international
      adoptees during the 60 days after their arrival should receive hepatitis A
      immunization, ideally 2 or more weeks before the arrival of the adopted child.

PMID- 21949137
TI  - Intermediate uveitis and alopecia areata: is there a relationship? Report of 3
      pediatric cases.
AB  - Three previously healthy children, aged 5, 8, and 15 years, with idiopathic
      intermediate uveitis (IU) and alopecia areata (AA) are described. These are the
      first 3 cases of which we are aware with this coexistence. The results of
      extensive diagnostic evaluations were negative in all 3 cases. AA preceded the
      diagnosis of bilateral IU in 1 child and followed within several months after IU
      diagnosis in 2 children. The severity of uveitis ranged from mild to sight
      threatening, and hair loss ranged from local lesions in 2 cases to total alopecia
      in 1 case. Pathogenesis of both diseases is discussed. Theoretically, the
      coexistence of IU and AA might be based on the similarities in their complex
      pathogenesis. However, more research is needed to evaluate if the coexistence is
      based on an association between 2 autoimmune disorders or is a coincidence.

PMID- 21949138
TI  - Parent-provider-community partnerships: optimizing outcomes for children with
      disabilities.
AB  - Children with disabilities and their families have multifaceted medical,
      developmental, educational, and habilitative needs that are best addressed
      through strong partnerships among parents, providers, and communities. However,
      traditional health care systems are designed to address acute rather than chronic
      conditions. Children with disabilities require high-quality medical homes that
      provide care coordination and transitional care, and their families require
      social and financial supports. Integrated community systems of care that promote
      participation of all children are needed. The purpose of this clinical report is
      to explore the challenges of developing effective community-based systems of care
      and to offer suggestions to pediatricians and policy-makers regarding the
      development of partnerships among children with disabilities, their families, and
      health care and other providers to maximize health and well-being of these
      children and their families.

PMID- 21949139
TI  - Molecular assays in the diagnosis of neonatal sepsis: a systematic review and
      meta-analysis.
AB  - BACKGROUND: Microbial cultures for diagnosis of neonatal sepsis suffer from low
      sensitivity and reporting delay. Advances in molecular microbiology have fostered
      new molecular assays that are rapid and may improve neonatal outcomes.
      OBJECTIVES: We assessed whether molecular assays have sufficient sensitivity
      (>0.98) and specificity (>0.95) to replace microbial cultures in the diagnosis of
      neonatal sepsis and explored heterogeneity by use of subgroup analyses based on
      the type of assay, gestational age of the neonate, and type of sepsis onset.
      METHODS: We performed the systematic review as recommended by the Cochrane
      Diagnostic Test Accuracy Working Group. Electronic bibliographic databases,
      conference abstracts, personal files, and reference lists of identified articles
      were searched. We included studies of case-control or consecutive series design,
      which evaluated molecular assays (index test) in neonates with suspected sepsis
      (participants) in comparison with microbial cultures (reference standard). Two
      reviewers independently assessed the methodologic quality of the studies and
      extracted data. RESULTS: A bivariate random-effects model was used for meta
      analysis of the 23 included studies, and summary estimates of sensitivity and
      specificity with 95% confidence intervals (CIs) were generated. Mean sensitivity
      and specificity were 0.90 (95% CI: 0.78-0.95) and 0.96 (95% CI: 0.94-0.97),
      respectively. Real-time polymerase chain reaction (PCR) and broad-range
      conventional PCR had higher sensitivity and specificity than other assays.
      Sufficient data were not available to evaluate gestational-age and sepsis-type
      subgroups. CONCLUSION: Molecular assays do not have sufficient sensitivity to
      replace microbial cultures in the diagnosis of neonatal sepsis but may perform
      well as "add-on" tests.

PMID- 21949140
TI  - Incidence of and risk factors for neonatal respiratory depression and
      encephalopathy in rural Sarlahi, Nepal.
AB  - OBJECTIVES: To characterize the incidence of, risk factors for, and neonatal
      morbidity and mortality associated with respiratory depression at birth and
      neonatal encephalopathy (NE) among term infants in a developing country. METHODS:
      Data were collected prospectively in 2002-2006 during a community-based trial
      that enrolled 23 662 newborns in rural Nepal and evaluated the impact of
      umbilical-cord and skin cleansing on neonatal morbidity and mortality rates.
      Respiratory depression at birth and NE were defined on the basis of symptoms from
      maternal reports and study-worker observations during home visits. RESULTS:
      Respiratory depression at birth was reported for 19.7% of live births, and 79% of
      cases involved term infants without congenital anomalies. Among newborns with
      probable intrapartum-related respiratory depression (N = 3465), 112 (3%) died
      before their first home visit (presumed severe NE), and 178 (5%) eventually
      developed symptoms of NE. Overall, 629 term infants developed NE (28.1 cases per
      1000 live births); 2% of cases were associated with congenital anomalies, 25%
      with infections, and 28% with a potential intrapartum event. The incidence of
      intrapartum-related NE was 13.0 cases per 1000 live births; the neonatal case
      fatality rate was 46%. Infants with NE more frequently experienced birth
      complications and were male, of multiple gestation, or born to nulliparous
      mothers. CONCLUSIONS: In Sarlahi, the incidence of neonatal respiratory
      depression and NE, associated neonatal case fatality, and morbidity prevalence
      are high. Action is required to increase coverage of skilled obstetric/neonatal
      care in this setting and to evaluate long-term impairments.

PMID- 21949141
TI  - National survey of neonatal transport teams in the United States.
AB  - OBJECTIVE: Neonatal transport in the United States is a complex process; however,
      little is known about the neonatal transport team (NTT) workforce. The purpose of
      this national study was to describe the US NTT workforce. PARTICIPANTS AND
      METHODS: An exploratory, descriptive design that used a Web-based survey
      questionnaire was used. We identified 398 NTTs, and 345 (86.7%) were enrolled.
      One survey was completed per team. RESULTS: Ten NTTs did not complete the survey
      (response rate: 84.2%). Of the 335 completed surveys, 229 (68.4%) were from unit
      based teams and 106 (31.6%) were from dedicated teams. Twenty-six different NTT
      compositions were used. All except 1 (n = 334) had a registered nurse or a
      neonatal nurse practitioner as a team member. A registered nurse-respiratory
      therapist team composition was the most common for unit-based (40.2%) and
      dedicated (44.3%) teams. Dedicated teams used rotor and fixed-wing modes of
      travel more frequently, transported further distances, and had higher transport
      volumes than unit-based teams. The median transport volumes reported suggest that
      as many as 68 797 critically ill neonates are transported each year. CONCLUSIONS:
      There is wide variation in many aspects of neonatal transport, including
      orientation, determination of readiness for independent transport, use of
      protocols to guide transport care, and quality assurance activities. These
      results will be useful for (1) evaluating existing transport services, (2)
      guiding necessary changes in training or services, and (3) aiding programs that
      seek to develop a neonatal transport program.

PMID- 21949142
TI  - Nonpharmacologic treatments for childhood constipation: systematic review.
AB  - OBJECTIVE: To summarize the evidence and assess the reported quality of studies
      concerning nonpharmacologic treatments for childhood constipation, including
      fiber, fluid, physical movement, prebiotics, probiotics, behavioral therapy,
      multidisciplinary treatment, and forms of alternative medicine. METHODS: We
      systematically searched 3 major electronic databases and reference lists of
      existing reviews. We included systematic reviews and randomized controlled trials
      (RCTs) that reported on nonpharmacologic treatments. Two reviewers rated the
      methodologic quality independently. RESULTS: We included 9 studies with 640
      children. Considerable heterogeneity across studies precluded meta-analysis. We
      found no RCTs for physical movement, multidisciplinary treatment, or alternative
      medicine. Some evidence shows that fiber may be more effective than placebo in
      improving both the frequency and consistency of stools and in reducing abdominal
      pain. Compared with normal fluid intake, we found no evidence that water intake
      increases or that hyperosmolar fluid treatment is more effective in increasing
      stool frequency or decreasing difficulty in passing stools. We found no evidence
      to recommend the use of prebiotics or probiotics. Behavioral therapy with
      laxatives is not more effective than laxatives alone. CONCLUSIONS: There is some
      evidence that fiber supplements are more effective than placebo. No evidence for
      any effect was found for fluid supplements, prebiotics, probiotics, or behavioral
      intervention. There is a lack of well-designed RCTs of high quality concerning
      nonpharmacologic treatments for children with functional constipation.

PMID- 21949143
TI  - Poliovirus.
AB  - Despite marked progress in global polio eradication, the threat of polio
      importation into the United States remains; therefore, all children should be
      protected against the disease. The standard schedule for poliovirus immunization
      remains 4 doses of inactivated poliovirus vaccine at 2, 4, and 6 through 18
      months and 4 through 6 years of age. The minimum interval between doses 1 and 2
      and between doses 2 and 3 is 4 weeks, and the minimum interval between doses 3
      and 4 is 6 months. The minimum age for dose 1 is 6 weeks. Minimal age and
      intervals should be used when there is imminent threat of exposure, such as
      travel to an area in which polio is endemic or epidemic. The final dose in the
      inactivated poliovirus vaccine series should be administered at 4 through 6 years
      of age, regardless of the previous number of doses administered before the fourth
      birthday, and at least 6 months since the last dose was received.

PMID- 21949145
TI  - Parental perceptions of weight terminology that providers use with youth.
AB  - OBJECTIVES: Little research has been performed to examine patient perceptions of
      weight-related language, especially related to childhood obesity. In this study
      we assessed parental perceptions of weight-based terminology used by health care
      providers to describe a child's excess weight and assessed perceived connotations
      associated with these terms including stigma, blame, and motivation to reduce
      weight. METHODS: A national sample of American parents with children aged 2 to 18
      years (N = 445) completed an online survey to assess their perceptions of 10
      common terms to describe excess body weight in youth (including "extremely
      obese," "high BMI," "weight problem," "unhealthy weight," "weight," "heavy,"
      "obese," "overweight," "chubby," and "fat"). Parents were asked to use a 5-point
      rating scale to indicate how much they perceived each term to be desirable,
      stigmatizing, blaming, or motivating to lose weight. RESULTS: Regression models
      revealed that the terms "weight" and "unhealthy weight" were rated as most
      desirable, and "unhealthy weight" and "weight problem" were rated as the most
      motivating to lose weight. The terms "fat," "obese," and "extremely obese" were
      rated as the most undesirable, stigmatizing, blaming, and least motivating.
      Parents' ratings were consistent across sociodemographic variables, body weight,
      and child's body weight. CONCLUSIONS: The results of this study have important
      implications for the improvement of health care for youth with obesity; it may be
      advantageous for health care providers to use or avoid using specific weight
      based language during discussions about body weight with families. Pediatricians
      play a key role in obesity prevention and treatment, but their efforts may be
      undermined by stigmatizing or offensive language that can hinder important
      discussions about children's health.

PMID- 21949146
TI  - Trends in US hospital distribution of industry-sponsored infant formula sample
      packs.
AB  - OBJECTIVE: To describe trends in the proportion of US hospitals that distribute
      industry-sponsored formula sample packs between 2007 and 2010. METHODS: This is a
      follow-up of a 2007 study. In 2007, we surveyed all 50 US states to determine the
      proportion of hospitals that distributed infant formula samples to new mothers.
      In 2010, we selected the 10 best-record and 10 worst-record states with regard to
      industry-sponsored formula sample-pack distribution in 2007. We called all
      hospitals in these 20 states and asked if the maternity service distributed a
      "formula company-sponsored diaper discharge bag" to new mothers. We also recorded
      the respondent's job title. RESULTS: We contacted 1239 hospitals in 20 states. In
      2007, 14% of these hospitals were sample-pack-free. In 2010, 28% of the same
      hospitals were sample-pack-free; the proportion of sample-pack-free hospitals per
      state ranged from 0% (5 states) to 86% (Rhode Island). In the 10 best-record
      states, the weighted proportion of sample-pack-free hospitals increased by a mean
      difference of 18% between 2007 and 2010 (P < .0001). In the 10 worst-record
      states, the weighted proportion of sample-pack-free hospitals increased by a mean
      difference of 6% (P < .01). CONCLUSION: Most US hospitals continue to distribute
      industry-sponsored formula sample packs, but trends indicate a significant change
      in practice; increasing proportions of hospitals eliminate these packs. Change
      was more significant in states where higher proportions of hospitals had already
      eliminated packs in 2007.

PMID- 21949144
TI  - Prevalence of asthma and its association with glycemic control among youth with
      diabetes.
AB  - OBJECTIVE: To estimate the prevalence of asthma among youth with types 1 and 2
      diabetes and examine associations between asthma and glycemic control. METHODS:
      This was a cross-sectional analysis of data from the SEARCH for Diabetes in Youth
      study, which included youth diagnosed with type 1 (n = 1683) and type 2 (n = 311)
      diabetes from 2002 through 2005. Asthma status and medications were ascertained
      from medical records and self-administered questionnaires, and glycemic control
      was assessed from hemoglobin A1c measured at the study visit. RESULTS: Prevalence
      of asthma among all youth with diabetes was 10.9% (95% confidence interval [CI]:
      9.6%-12.3%). The prevalence was 10.0% (95% CI: 8.6%-11.4%) among youth with type
      1 and 16.1% (95% CI: 12.0%-20.2%) among youth with type 2 diabetes and differed
      according to race/ethnicity. Among youth with type 1 diabetes, those with asthma
      had higher mean A1c levels than those without asthma, after adjustment for age,
      gender, race/ethnicity, and BMI (7.77% vs 7.49%; P = .034). Youth with asthma
      were more likely to have poor glycemic control, particularly those with type 1
      diabetes whose asthma was not treated with pharmacotherapy, although this
      association was attenuated by adjustment for race/ethnicity. CONCLUSIONS:
      Prevalence of asthma may be elevated among youth with diabetes relative to the
      general US population. Among youth with type 1 diabetes, asthma is associated
      with poor glycemic control, especially if asthma is untreated. Specific asthma
      medications may decrease systemic inflammation, which underlies the complex
      relationship between pulmonary function, BMI, and glycemic control among youth
      with diabetes.

PMID- 21949147
TI  - Overestimating neuroprotection in congenital heart disease: problems with Bayley
      III outcomes.

PMID- 21949148
TI  - Overestimating neurodevelopment using the Bayley-III after early complex cardiac
      surgery.
AB  - BACKGROUND: The newest measure of neurodevelopmental outcomes, the Bayley Scales
      of Infant and Toddler Development, 3rd Edition (Bayley-III), gives higher-than
      expected scores for preterm infants; results after cardiac surgery are unknown.
      OBJECTIVES: The goal of this study was to report Bayley-III scores after cardiac
      surgery and compare the results with those of the Bayley Scales of Infant
      Development, 2nd Edition (BSID-II) on a subset of the same children. METHODS: In
      this prospective, inception cohort, neurodevelopmental outcome study after
      complex cardiac surgery in infants from 2004 to 2007, the Bayley-III was given to
      110 survivors (68% boys) at a mean age of 21 months (SD: 4 months). Analysis of
      variance was used to compare intergroup differences. Results for both test
      editions on the same 25 children were compared by using paired-samples
      statistics. RESULTS: Mean (SD) Bayley-III mean composite scores (CSs) for 110
      children were as follows: cognitive, 95.9 (14.1); language, 90.8 (18.1); and
      motor, 93.7 (14.2), differentiating selected cardiac surgery groups. The average
      difference in mean CSs was 7.4 points higher than BSID-II scores for a previous
      cohort from this site and 7.2 points higher than a systematic review report.
      Direct comparison of BSID-II and Bayley-III revealed an average difference in
      mean CSs of 6.1 points, similar to normative results. Mean cognitive CSs
      increased by 10.0 (P <.001), language by 1.4 (P = .526), and motor by 6.9 points
      (P = .009). CONCLUSIONS: Researchers should be careful attributing higher Bayley
      III scores to changes in acute care. At-risk children who previously qualified
      for early developmental intervention may no longer do so. School-age longitudinal
      studies are needed to determine the accuracy of early developmental estimates
      using the Bayley-III.

PMID- 21949149
TI  - Randomized clinical trial of rapid versus 24-hour rehydration for children with
      acute gastroenteritis.
AB  - OBJECTIVE: To compare the efficacy of 2 nasogastric rehydration regimens for
      children with acute viral gastroenteritis. METHODS: Children 6 to 72 months of
      age with acute viral gastroenteritis and moderate dehydration were recruited from
      emergency departments (EDs) at 2 metropolitan, pediatric, teaching hospitals.
      After clinical assessment of the degree of dehydration, patients were assigned
      randomly to receive either standard nasogastric rehydration (SNR) over 24 hours
      in the hospital ward or rapid nasogastric rehydration (RNR) over 4 hours in the
      ED. Primary (>2% weight loss, compared with the admission weight) and secondary
      treatment failures were assessed. RESULTS: Of 9331 children with acute
      gastroenteritis who were screened, 254 children were assigned randomly to receive
      either RNR (n = 132 [52.0%]) or SNR (n = 122 [48.0%]). Baseline characteristics
      for the 2 groups were similar. All patients made a full recovery without severe
      adverse events. The primary failure rates were similar for RNR (11.8% [95%
      confidence interval [CI]: 6.0%-17.6%]) and SNR (9.2% [95% CI: 3.7%-14.7%]; P =
      .52). Secondary treatment failure was more common in the SNR group (44% [95% CI:
      34.6%-53.4%]) than in the RNR group (30.3% [95% CI: 22.5%-38.8%]; P = .03).
      Discharge from the ED after RNR failed for 27 patients (22.7%), and another 9
      (7.6%) were readmitted to the hospital within 24 hours. CONCLUSIONS: Primary
      treatment failure and clinical outcomes were similar for RNR and SNR. Although
      RNR generally reduced the need for hospitalization, discharge home from the ED
      failed for approximately one-fourth of the patients.

PMID- 21949150
TI  - Phototherapy to prevent severe neonatal hyperbilirubinemia in the newborn infant
      35 or more weeks of gestation.
AB  - OBJECTIVE: To standardize the use of phototherapy consistent with the American
      Academy of Pediatrics clinical practice guideline for the management of
      hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. METHODS:
      Relevant literature was reviewed. Phototherapy devices currently marketed in the
      United States that incorporate fluorescent, halogen, fiber-optic, or blue light
      emitting diode light sources were assessed in the laboratory. RESULTS: The
      efficacy of phototherapy units varies widely because of differences in light
      source and configuration. The following characteristics of a device contribute to
      its effectiveness: (1) emission of light in the blue-to-green range that overlaps
      the in vivo plasma bilirubin absorption spectrum (~460-490 nm); (2) irradiance of
      at least 30 MUW . cm(-2) . nm(-1) (confirmed with an appropriate irradiance meter
      calibrated over the appropriate wavelength range); (3) illumination of maximal
      body surface; and (4) demonstration of a decrease in total bilirubin
      concentrations during the first 4 to 6 hours of exposure. RECOMMENDATIONS (SEE
      APPENDIX FOR GRADING DEFINITION): The intensity and spectral output of
      phototherapy devices is useful in predicting potential effectiveness in treating
      hyperbilirubinemia (group B recommendation). Clinical effectiveness should be
      evaluated before and monitored during use (group B recommendation). Blocking the
      light source or reducing exposed body surface should be avoided (group B
      recommendation). Standardization of irradiance meters, improvements in device
      design, and lower-upper limits of light intensity for phototherapy units merit
      further study. Comparing the in vivo performance of devices is not practical, in
      general, and alternative procedures need to be explored.

PMID- 21949151
TI  - Additional recommendations for use of tetanus toxoid, reduced-content diphtheria
      toxoid, and acellular pertussis vaccine (Tdap).
AB  - The American Academy of Pediatrics and the Centers for Disease Control and
      Prevention are amending previous recommendations and making additional
      recommendations for the use of tetanus toxoid, reduced-content diphtheria toxoid,
      and acellular pertussis vaccine (Tdap). Review of the results from clinical
      trials and other studies has revealed no excess reactogenicity when Tdap is given
      within a short interval after other tetanus- or diphtheria-containing toxoid
      products, and accrual of postmarketing adverse-events reports reveals an
      excellent safety record for Tdap. Thus, the recommendation for caution regarding
      Tdap use within any interval after a tetanus- or diphtheria-containing toxoid
      product is removed. Tdap should be given when it is indicated and when no
      contraindication exists. In further efforts to protect people who are susceptible
      to pertussis, the American Academy of Pediatrics and Centers for Disease Control
      and Prevention recommend a single dose of Tdap for children 7 through 10 years of
      age who were underimmunized with diphtheria-tetanus-acellular pertussis (DTaP).
      Also, the age for recommendation for Tdap is extended to those aged 65 years and
      older who have or are likely to have contact with an infant younger than 12
      months (eg, health care personnel, grandparents, and other caregivers).

PMID- 21949152
TI  - The use of systemic and topical fluoroquinolones.
AB  - Appropriate prescribing practices for fluoroquinolones are essential as evolving
      resistance patterns are considered, additional treatment indications are
      identified, and the toxicity profile of fluoroquinolones in children becomes
      better defined. Earlier recommendations for systemic therapy remain; expanded
      uses of fluoroquinolones for the treatment of certain infections are outlined in
      this report. Although fluoroquinolones are reasonably safe in children,
      clinicians should be aware of the specific adverse reactions. Use of
      fluoroquinolones in children should continue to be limited to treatment of
      infections for which no safe and effective alternative exists.

PMID- 21949154
TI  - Phosphodiesterase 4 inhibition attenuates persistent heart and lung injury by
      neonatal hyperoxia in rats.
AB  - Phosphodiesterase (PDE) 4 inhibitors are potent anti-inflammatory drugs with
      antihypertensive properties, and their therapeutic role in bronchopulmonary
      dysplasia (BPD) is still controversial. We studied the role of PDE4 inhibition
      with piclamilast on normal lung development and its therapeutic value on
      pulmonary hypertension (PH) and right ventricular hypertrophy (RVH) in neonatal
      rats with hyperoxia-induced lung injury, a valuable model for premature infants
      with severe BPD. The cardiopulmonary effects of piclamilast treatment (5 mg.kg(
      1).day(-1)) were investigated in two models of experimental BPD: 1) daily
      treatment during continuous exposure to hyperoxia for 10 days; and 2) late
      treatment and injury-recovery in which pups were exposed to hyperoxia or room air
      for 9 days, followed by 9 or 42 days of recovery in room air combined with
      treatment started on day 6 of oxygen exposure until day 18. Prophylactic
      piclamilast treatment reduced pulmonary fibrin deposition, septum thickness,
      arteriolar wall thickness, arteriolar vascular smooth muscle cell proliferation
      and RVH, and prolonged survival. In the late treatment and injury-recovery model,
      hyperoxia caused persistent aberrant alveolar and vascular development, PH, and
      RVH. Treatment with piclamilast in both models reduced arteriolar wall thickness,
      attenuated RVH, and improved right ventricular function in the injury recovery
      model, but did not restore alveolarization or angiogenesis. Treatment with
      piclamilast did not show adverse cardiopulmonary effects in room air controls in
      both models. In conclusion, PDE4 inhibition attenuated and partially reversed PH
      and RVH, but did not advance alveolar development in neonatal rats with hyperoxic
      lung injury or affect normal lung and heart development.

PMID- 21949155
TI  - Regulation and function of the two-pore-domain (K2P) potassium channel Trek-1 in
      alveolar epithelial cells.
AB  - Hyperoxia can lead to a myriad of deleterious effects in the lung including
      epithelial damage and diffuse inflammation. The specific mechanisms by which
      hyperoxia promotes these pathological changes are not completely understood.
      Activation of ion channels has been proposed as one of the mechanisms required
      for cell activation and mediator secretion. The two-pore-domain K(+) channel
      (K2P) Trek-1 has recently been described in lung epithelial cells, but its
      function remains elusive. In this study we hypothesized that hyperoxia affects
      expression of Trek-1 in alveolar epithelial cells and that Trek-1 is involved in
      regulation of cell proliferation and cytokine secretion. We found gene expression
      of several K2P channels in mouse alveolar epithelial cells (MLE-12), and
      expression of Trek-1 was significantly downregulated in cultured cells and lungs
      of mice exposed to hyperoxia. Similarly, proliferation cell nuclear antigen
      (PCNA) and Cyclin D1 expression were downregulated by exposure to hyperoxia. We
      developed an MLE-12 cell line deficient in Trek-1 expression using shRNA and
      found that Trek-1 deficiency resulted in increased cell proliferation and
      upregulation of PCNA but not Cyclin D1. Furthermore, IL-6 and regulated on
      activation normal T-expressed and presumably secreted (RANTES) secretion was
      decreased in Trek-1-deficient cells, whereas release of monocyte chemoattractant
      protein-1 was increased. Release of KC/IL-8 was not affected by Trek-1
      deficiency. Overall, deficiency of Trek-1 had a more pronounced effect on
      mediator secretion than exposure to hyperoxia. This is the first report
      suggesting that the K(+) channel Trek-1 could be involved in regulation of
      alveolar epithelial cell proliferation and cytokine secretion, but a direct
      association with hyperoxia-induced changes in Trek-1 levels remains elusive.

PMID- 21949153
TI  - Arabidopsis RTNLB1 and RTNLB2 Reticulon-like proteins regulate intracellular
      trafficking and activity of the FLS2 immune receptor.
AB  - Receptors localized at the plasma membrane are critical for the recognition of
      pathogens. The molecular determinants that regulate receptor transport to the
      plasma membrane are poorly understood. In a screen for proteins that interact
      with the FLAGELIN-SENSITIVE2 (FLS2) receptor using Arabidopsis thaliana protein
      microarrays, we identified the reticulon-like protein RTNLB1. We showed that FLS2
      interacts in vivo with both RTNLB1 and its homolog RTNLB2 and that a Ser-rich
      region in the N-terminal tail of RTNLB1 is critical for the interaction with
      FLS2. Transgenic plants that lack RTNLB1 and RTNLB2 (rtnlb1 rtnlb2) or
      overexpress RTNLB1 (RTNLB1ox) exhibit reduced activation of FLS2-dependent
      signaling and increased susceptibility to pathogens. In both rtnlb1 rtnlb2 and
      RTNLB1ox, FLS2 accumulation at the plasma membrane was significantly affected
      compared with the wild type. Transient overexpression of RTNLB1 led to FLS2
      retention in the endoplasmic reticulum (ER) and affected FLS2 glycosylation but
      not FLS2 stability. Removal of the critical N-terminal Ser-rich region or either
      of the two Tyr-dependent sorting motifs from RTNLB1 causes partial reversion of
      the negative effects of excess RTNLB1 on FLS2 transport out of the ER and
      accumulation at the membrane. The results are consistent with a model whereby
      RTNLB1 and RTNLB2 regulate the transport of newly synthesized FLS2 to the plasma
      membrane.

PMID- 21949156
TI  - Targeting the restricted alpha-subunit repertoire of airway smooth muscle GABAA
      receptors augments airway smooth muscle relaxation.
AB  - The prevalence of asthma has taken on pandemic proportions. Since this disease
      predisposes patients to severe acute airway constriction, novel mechanisms
      capable of promoting airway smooth muscle relaxation would be clinically
      valuable. We have recently demonstrated that activation of endogenous airway
      smooth muscle GABA(A) receptors potentiates beta-adrenoceptor-mediated
      relaxation, and molecular analysis of airway smooth muscle reveals that the alpha
      subunit component of these GABA(A) receptors is limited to the alpha(4)- and
      alpha(5)-subunits. We questioned whether ligands with selective affinity for
      these GABA(A) receptors could promote relaxation of airway smooth muscle. RT-PCR
      analysis of GABA(A) receptor subunits was performed on RNA isolated by laser
      capture microdissection from human and guinea pig airway smooth muscle. Membrane
      potential and chloride-mediated current were measured in response to GABA(A)
      subunit-selective agonists in cultured human airway smooth muscle cells.
      Functional relaxation of precontracted guinea pig tracheal rings was assessed in
      the absence and presence of the alpha(4)-subunit-selective GABA(A) receptor
      agonists: gaboxadol, taurine, and a novel 8-methoxy imidazobenzodiazepine (CM-D
      45). Only messenger RNA encoding the alpha(4)- and alpha(5)-GABA(A) receptor
      subunits was identified in RNA isolated by laser capture dissection from guinea
      pig and human airway smooth muscle tissues. Activation of airway smooth muscle
      GABA(A) receptors with agonists selective for these subunits resulted in
      appropriate membrane potential changes and chloride currents and promoted
      relaxation of airway smooth muscle. In conclusion, selective subunit targeting of
      endogenous airway smooth muscle-specific GABA(A) receptors may represent a novel
      therapeutic option for patients in severe bronchospasm.

PMID- 21949159
TI  - Just listen.

PMID- 21949157
TI  - Contributions of TRPV1, endovanilloids, and endoplasmic reticulum stress in lung
      cell death in vitro and lung injury.
AB  - Endogenous agonists of transient receptor potential vanilloid-1 (TRPV1)
      (endovanilloids) are implicated as mediators of lung injury during inflammation.
      This study tested the hypothesis that endovanilloids produced following
      lipopolysaccharide (LPS) treatment activate TRPV1 and cause endoplasmic reticulum
      stress/GADD153 expression in lung cells, representing a mechanistic component of
      lung injury. The TRPV1 agonist nonivamide induced GADD153 expression and caused
      cytotoxicity in immortalized and primary human bronchial, bronchiolar/alveolar,
      and microvascular endothelial cells, proportional to TRPV1 mRNA expression. In CF
      1 mice, Trpv1 mRNA was most abundant in the alveoli, and intratracheal nonivamide
      treatment promoted Gadd153 expression in the alveolar region. Treatment of CF-1
      mice with LPS increased Gadd153 in the lung, lactate dehydrogenase (LDH) in
      bronchoalveolar lavage (BAL) fluid, and lung wet-to-dry weight ratio. Cotreating
      mice with LPS and the TRPV1 antagonist LJO-328 reduced Gadd153 induction and LDH
      in BAL but did not inhibit increases in lung wet-to-dry ratio. In Trpv1(-/-) mice
      treated with LPS, Gadd153 induction and LDH in BAL were reduced relative to wild
      type mice, and the wet-to-dry weight ratios of lungs from both wild-type and
      Trpv1(-/-) mice decreased. Organic extracts of blood collected from LPS-treated
      mice were more cytotoxic to TRPV1-overexpressing cells compared with BEAS-2B
      cells and extracts from control mice, however, most pure endovanilloids did not
      produce cytotoxicity in a characteristic TRPV1-dependent manner. Collectively,
      these data indicate a role for TRPV1, and endogenous TRPV1 agonists, in ER stress
      and cytotoxicity in lung cells but demonstrate that ER stress and cytotoxicity
      are not essential for pulmonary edema.

PMID- 21949158
TI  - Physiological effect of protein kinase C on ENaC-mediated lung liquid regulation
      in the adult rat lung.
AB  - Tight control of lung liquid (LL) regulation is vital for pulmonary function. The
      aim of this work was to determine whether PKC activation is involved in the
      physiological regulation of LL volume in a whole lung preparation. Rat lungs were
      perfused with a modified Ringer solution, and the lumen was filled with the same
      solution without glucose. LL volume was measured during a control period and
      after modulating drugs were administered, and net LL transepithelial movement
      (J(v)) was calculated. When the PKC activator PMA (10(-5) M) and the Ca(2+)
      ionophore ionomycin (10(-6) M) were instilled into the lung together, J(v) was
      significantly reduced (P = 0.03). This reduction was blocked by the PKC inhibitor
      chelerythrine chloride (10(-6) M; P = 0.56) and by a second PKC inhibitor
      GF109203X (10(-5) M; P = 0.98). When PMA and ionomycin were added with the beta
      adrenergic agonist terbutaline, the terbutaline-induced increase in J(v) was
      abolished. Addition of PMA and ionomycin with the epithelial Na(+) channel (ENaC)
      blocker amiloride had no additional inhibitory effect. Together, these results
      suggest that PKC is likely to be involved in LL absorption, and the ability of
      PMA/ionomycin to block the terbutaline-induced increase in J(v) suggests that the
      downstream target of PKC is ENaC.

PMID- 21949160
TI  - Peace at the end.

PMID- 21949161
TI  - Encounter frequency and serum glucose level, blood pressure, and cholesterol
      level control in patients with diabetes mellitus.
AB  - BACKGROUND: More frequent patient-provider encounters may lead to faster control
      of hemoglobin A1c level, blood pressure (BP), and low-density lipoprotein (LDL)
      cholesterol (LDL-C) level (hereafter referred to as hemoglobin A1c, BP, and LDL
      C) and improve outcomes, but no guidelines exist for how frequently patients with
      diabetes mellitus (DM) should be seen. METHODS: This retrospective cohort study
      analyzed 26,496 patients with diabetes and elevated hemoglobin A1c, BP, and/or
      LDL-C treated by primary care physicians at 2 teaching hospitals between January
      1, 2000, and January 1, 2009. The relationship between provider encounter
      (defined as a note in the medical record) frequency and time to hemoglobin A1c,
      BP, and LDL-C control was assessed. RESULTS: Comparing patients who had
      encounters with their physicians between 1 to 2 weeks vs 3 to 6 months, median
      time to hemoglobin A1c less than 7.0% was 4.4 vs 24.9 months (not receiving
      insulin) and 10.1 vs 52.8 months (receiving insulin); median time to BP lower
      than 130/85 mm Hg was 1.3 vs 13.9 months; and median time to LDL-C less than 100
      mg/dL was 5.1 vs 32.8 months, respectively (P<.001 for all). In multivariable
      analysis, doubling the time between physician encounters led to an increase in
      median time to hemoglobin A1c (not receiving [35%] and receiving [17%] insulin),
      BP (87%), and LDL-C (27%) targets (P<.001 for all). Time to control decreased
      progressively as encounter frequency increased up to once every 2 weeks for most
      targets, consistent with the pharmacodynamics of the respective medication
      classes. CONCLUSIONS: Primary care provider encounters every 2 weeks are
      associated with fastest achievement of hemoglobin A1c, BP, and LDL-C targets for
      patients with diabetes mellitus.

PMID- 21949162
TI  - When it comes to primary care, more may be more: comment on "Encounter frequency
      and serum glucose level, blood pressure, and cholesterol level control in
      patients with diabetes mellitus".

PMID- 21949163
TI  - Electronic medical record reminders and panel management to improve primary care
      of elderly patients.
AB  - BACKGROUND: Most elderly patients do not receive recommended preventive care,
      acute care, and care for chronic conditions. METHODS: We conducted a controlled
      trial to assess the effectiveness of electronic medical record (EMR) reminders,
      with or without panel management, on health care proxy designation, osteoporosis
      screening, and influenza and pneumococcal vaccinations in patients older than 65
      years. Physicians were assigned to 1 of the following 3 arms: EMR reminder, EMR
      reminder plus panel manager, or control. We assessed completion of recommended
      practices during a 1-year period. RESULTS: Among patients who had not already
      received the recommended care, health care proxy was designated in 6.5% of
      patients in the control arm, 8.8% of the EMR reminder arm, and 19.7% of the EMR
      reminder plus panel manager arm (P=.002). Bone density screening was completed in
      17.7% of patients in the control arm, 19.7% of the EMR reminder arm, and 30.5% of
      the EMR reminder plus panel manager arm (P=.02). Pneumococcal vaccine was given
      to 13.1% of patients in the control arm, 19.5% of the EMR reminder arm, and 25.6%
      of the EMR reminder plus panel manager arm (P=.02). Influenza vaccine was given
      to 46.8% of patients in the control arm, 56.5% of the EMR reminder arm, and 59.7%
      of the EMR reminder plus panel manager arm (P=.002). Results were similar when
      adjusted for individual physician performance in the preceding year, patient age,
      patient sex, years cared for by the practice, and number of visits. CONCLUSIONS:
      Electronic medical record reminders alone facilitated improvement in vaccination
      rates and, when augmented by panel management, facilitated further improvement in
      vaccination rates and boosted the rates of health care proxy designation and bone
      density screening. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT01313169.

PMID- 21949164
TI  - Improving population health through team-based panel management: comment on
      "Electronic medical record reminders and panel management to improve primary care
      of elderly patients".

PMID- 21949166
TI  - HAART for HIV-1 infection: zeroing in on when to start: comment on "Timing of
      HAART initiation and clinical outcomes in human immunodeficiency virus type 1
      seroconverters".

PMID- 21949165
TI  - Timing of HAART initiation and clinical outcomes in human immunodeficiency virus
      type 1 seroconverters.
AB  - BACKGROUND: To estimate the clinical benefit of highly active antiretroviral
      therapy (HAART) initiation vs deferral in a given month in patients with CD4 cell
      counts less than 800/MUL. METHODS: In this observational cohort study of human
      immunodeficiency virus type 1 seroconverters from CASCADE (Concerted Action on
      SeroConversion to AIDS and Death in Europe), we constructed monthly sequential
      nested subcohorts between January 1996 and May 2009, including all eligible HAART
      naive, AIDS-free individuals with a CD4 cell count less than 800/MUL. The primary
      outcome was time to AIDS or death in those who initiated HAART in the baseline
      month compared with those who did not, pooled across subcohorts and stratified by
      CD4 cell count. Using inverse probability-of-treatment weighted survival curves
      and Cox proportional hazards regression models, we estimated the absolute and
      relative effects of treatment with robust 95% confidence intervals (CIs).
      RESULTS: Of 9455 patients with 52,268 person-years of follow-up, 812 (8.6%)
      developed AIDS and 544 (5.8%) died. In CD4 cell count strata of 200 to 349, 350
      to 499, and 500 to 799/MUL, HAART initiation was associated with adjusted hazard
      ratios (95% CIs) for AIDS/death of 0.59 (0.43-0.81), 0.75 (0.49-1.14), and 1.10
      (0.67-1.79), respectively. In the analysis of all-cause mortality, HAART
      initiation was associated with adjusted hazard ratios (95% CIs) of 0.71 (0.44
      1.15), 0.51 (0.33-0.80), and 1.02 (0.49-2.12), respectively. Numbers needed to
      treat (95% CIs) to prevent 1 AIDS event or death within 3 years were 21 (14-38)
      and 34 (20-115) in CD4 cell count strata of 200 to 349 and 350 to 499/MUL,
      respectively. CONCLUSION: Compared with deferring in a given month, HAART
      initiation at CD4 cell counts less than 500/MUL (but not 500-799/MUL) was
      associated with slower disease progression.

PMID- 21949167
TI  - Coffee, caffeine, and risk of depression among women.
AB  - BACKGROUND: Caffeine is the world's most widely used central nervous system
      stimulant, with approximately 80% consumed in the form of coffee. However,
      studies that analyze prospectively the relationship between coffee or caffeine
      consumption and depression risk are scarce. METHODS: A total of 50,739 US women
      (mean age, 63 years) free of depressive symptoms at baseline (in 1996) were
      prospectively followed up through June 1, 2006. Consumption of caffeine was
      measured from validated questionnaires completed from May 1, 1980, through April
      1, 2004, and computed as cumulative mean consumption with a 2-year latency period
      applied. Clinical depression was defined as self-reported physician-diagnosed
      depression and antidepressant use. Relative risks of clinical depression were
      estimated using Cox proportional hazards regression models. RESULTS: During 10
      years of follow-up (1996-2006), 2607 incident cases of depression were
      identified. Compared with women consuming 1 or less cup of caffeinated coffee per
      week, the multivariate relative risk of depression was 0.85 (95% confidence
      interval, 0.75-0.95) for those consuming 2 to 3 cups per day and 0.80 (0.64-0.99;
      P for trend<.001) for those consuming 4 cups per day or more. Multivariate
      relative risk of depression was 0.80 (95% confidence interval, 0.68-0.95; P for
      trend=.02) for women in the highest (>=550 mg/d) vs lowest (<100 mg/d) of the 5
      caffeine consumption categories. Decaffeinated coffee was not associated with
      depression risk. CONCLUSIONS: In this large longitudinal study, we found that
      depression risk decreases with increasing caffeinated coffee consumption. Further
      investigations are needed to confirm this finding and to determine whether usual
      caffeinated coffee consumption can contribute to depression prevention.

PMID- 21949168
TI  - Coffee consumption and depression risk: comment on "coffee, caffeine, and risk of
      depression among women".

PMID- 21949169
TI  - Too Little? Too Much? Primary care physicians' views on US health care: a brief
      report.
AB  - BACKGROUND: Some believe that a substantial amount of US health care is
      unnecessary, suggesting that it would be possible to control costs without
      rationing effective services. The views of primary care physicians-the frontline
      of health care delivery-are not known. METHODS: Between June and December 2009,
      we conducted a nationally representative mail survey of US primary care
      physicians (general internal medicine and family practice) randomly selected from
      the American Medical Association Physician Masterfile (response rate, 70%;
      n=627). RESULTS: Forty-two percent of US primary care physicians believe that
      patients in their own practice are receiving too much care; only 6% said they
      were receiving too little. The most important factors physicians identified as
      leading them to practice more aggressively were malpractice concerns (76%),
      clinical performance measures (52%), and inadequate time to spend with patients
      (40%). Physicians also believe that financial incentives encourage aggressive
      practice: 62% said diagnostic testing would be reduced if it did not generate
      revenue for medical subspecialists (39% for primary care physicians). Almost all
      physicians (95%) believe that physicians vary in what they would do for identical
      patients; 76% are interested in learning how aggressive or conservative their own
      practice style is compared with that of other physicians in their community.
      CONCLUSIONS: Many US primary care physicians believe that their own patients are
      receiving too much medical care. Malpractice reform, realignment of financial
      incentives, and more time with patients could remove pressure on physicians to do
      more than they feel is needed. Physicians are interested in feedback on their
      practice style, suggesting they may be receptive to change. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00853918.

PMID- 21949170
TI  - Nice work if you can get it: comment on "Too little? Too much? Primary care
      physicians' views on US health care".

PMID- 21949171
TI  - Reasons for overtreatment: comment on "Too little? Too much? Primary care
      physicians' views on US health care".

PMID- 21949172
TI  - Role of transfusion in the development of urinary tract-related bloodstream
      infection.

PMID- 21949173
TI  - Variations in structure and content of online social networks for patients with
      diabetes.

PMID- 21949174
TI  - Black/White racial disparities in health: a cross-country comparison of Canada
      and the United States.

PMID- 21949175
TI  - Making the case for selective use of statins in the primary prevention setting.

PMID- 21949176
TI  - Editor's Note--to make the case--evidence is required: comment on "Making the
      case for selective use of statins in the primary prevention setting".

PMID- 21949177
TI  - Needed assumptions for potential savings from greater use of $4 generic drugs.

PMID- 21949178
TI  - The true cost of discounted medication programs.

PMID- 21949179
TI  - Long-term renal outcomes of patients with type 1 diabetes mellitus and
      microalbuminuria: an analysis of the DCCT/EDIC cohort.

PMID- 21949180
TI  - Is reducing home health a step in the right direction?

PMID- 21949181
TI  - The proactive management of "relationship with industry" by ACC/AHA in the
      creation of our cardiovascular clinical practice guidelines.

PMID- 21949182
TI  - Ignorance is bliss?

PMID- 21949183
TI  - Palliative care units: the best option for the most distressed.

PMID- 21949184
TI  - Intracellular K+ concentration decrease is not obligatory for apoptosis.
AB  - K(+) efflux is observed as an early event in the apoptotic process in various
      cell types. Loss of intracellular K(+) and subsequent reduction in ionic strength
      are suggested to release the inhibition of proapoptotic caspases. In this work, a
      new K(+)-specific microelectrode was used to study possible alterations in
      intracellular K(+) in Xenopus laevis oocytes during chemically induced apoptosis.
      The accuracy of the microelectrode to detect changes in intracellular K(+) was
      verified with parallel electrophysiological measurements. In concordance with
      previous studies on other cell types, apoptotic stimuli reduced the intracellular
      K(+) concentration in Xenopus oocytes and increased caspase-3 activity. The
      reduction in intracellular K(+) was prevented by dense expression of voltage
      gated K (Kv) channels. Despite this, the caspase-3 activity was increased
      similarly in Kv channel-expressing oocytes as in oocytes not expressing Kv
      channels. Thus, in Xenopus oocytes caspase-3 activity is not dependent on the
      intracellular concentration of K(+).

PMID- 21949185
TI  - The leucine zipper putative tumor suppressor 2 protein LZTS2 regulates kidney
      development.
AB  - Members of the leucine zipper putative tumor suppressor (LZTS) family play
      crucial roles in transcription modulation and cell cycle control. We previously
      demonstrated that LZTS2 functions as a novel beta-catenin-interacting protein and
      represses beta-catenin-mediated transcription on T-cell factor/lymphoid enhancing
      factor. Here, we investigate the biological role of LZTS2 using newly established
      Lzts2 KO mice. Homozygosity for loss-of-function of the Lzts2-targeted allele
      resulted in severe kidney and urinary tract developmental defects, including
      renal/ureteral duplication, hydroureter, and hydronephrosis, which were visible
      prenatally. Altered ureteric bud outgrowth was identified in Lzts2 null embryos.
      Further analysis indicated that beta-catenin subcellular localization was altered
      in fibroblasts isolated from Lzts2 null embryos. In addition, Wnt growth factor
      induced beta-catenin-mediated transcriptional activity was increased in Lzts2
      null fibroblasts, suggesting a direct role for Lzts2 in the Wnt signaling
      pathway. These data demonstrate a critical role of LZTS2 in renal development and
      implicate LZTS2 as a critical regulator of beta-catenin-mediated nephrogenesis.

PMID- 21949186
TI  - Evolutionary remodeling of betagamma-crystallins for domain stability at cost of
      Ca2+ binding.
AB  - The topologically similar betagamma-crystallins that are prevalent in all
      kingdoms of life have evolved for high innate domain stability to perform their
      specialized functions. The evolution of stability and its control in betagamma
      crystallins that possess either a canonical (mostly from microorganisms) or
      degenerate (principally found in vertebrate homologues) Ca2+-binding motif is not
      known. Using equilibrium unfolding of betagamma-crystallin domains (26 wild-type
      domains and their mutants) in apo- and holo-forms, we demonstrate the presence of
      a stability gradient across these members, which is attained by the choice of
      residues in the (N/D)(N/D)XX(S/T)S Ca2+-binding motif. The occurrence of a polar,
      hydrophobic, or Ser residue at the 1st, 3rd, or 5th position of the motif is
      likely linked to a higher domain stability. Partial conversion of a microbe-type
      domain (with a canonical Ca2+-binding motif) to a vertebrate-type domain (with a
      degenerate Ca2+-binding motif) by mutating serine to arginine/lysine disables the
      Ca2+-binding but significantly augments its stability. Conversely, stability is
      compromised when arginine (in a vertebrate-type disabled domain) is replaced by
      serine (as a microbe type). Our results suggest that such conversions were
      acquired as a strategy for desired stability in vertebrate members at the cost of
      Ca2+-binding. In a physiological context, we demonstrate that a mutation such as
      an arginine to serine (R77S) mutation in this motif of gamma-crystallin (partial
      conversion to microbe-type), implicated in cataracts, decreases the domain
      stability. Thus, this motif acts as a "central tuning knob" for innate as well as
      Ca2+-induced gain in stability, incorporating a stability gradient across
      betagamma-crystallin members critical for their specialized functions.

PMID- 21949187
TI  - Deciphering the Xcp Pseudomonas aeruginosa type II secretion machinery through
      multiple interactions with substrates.
AB  - The type II secretion system enables gram-negative bacteria to secrete
      exoproteins into the extracellular milieu. We performed biophysical and
      biochemical experiments to identify systematic interactions between Pseudomonas
      aeruginosa Xcp type II secretion system components and their substrates. We
      observed that three Xcp components, XcpP(C), the secretin XcpQ(D), and the
      pseudopilus tip, directly and specifically interact with secreted exoproteins. We
      established that XcpP(C), in addition to its interaction with the substrate,
      likely shields the entire periplasmic portion of the secreton. It can therefore
      be considered as the recruiter of the machinery. Moreover, the direct interaction
      observed between the substrate and the pseudopilus tip validates the piston model
      hypothesis, in which the pseudopilus pushes the substrate through the secretin
      pore during the secretion process. All together, our results allowed us to
      propose a model of the different consecutive steps followed by the substrate
      during the type II secretion process.

PMID- 21949188
TI  - Single amino acid residue in the A2 domain of major histocompatibility complex
      class I is involved in the efficiency of equine herpesvirus-1 entry.
AB  - Equine herpesvirus-1 (EHV-1), an alpha-herpesvirus of the family Herpesviridae,
      causes respiratory disease, abortion, and encephalomyelitis in horses. EHV-1
      utilizes equine MHC class I molecules as entry receptors. However, hamster MHC
      class I molecules on EHV-1-susceptible CHO-K1 cells play no role in EHV-1 entry.
      To identify the MHC class I molecule region that is responsible for EHV-1 entry,
      domain exchange and site-directed mutagenesis experiments were performed, in
      which parts of the extracellular region of hamster MHC class I (clone C5) were
      replaced with corresponding sequences from equine MHC class I (clone A68).
      Substitution of alanine for glutamine at position 173 (Q173A) within the alpha2
      domain of the MHC class I molecule enabled hamster MHC class I C5 to mediate EHV
      1 entry into cells. Conversely, substitution of glutamine for alanine at position
      173 (A173Q) in equine MHC class I A68 resulted in loss of EHV-1 receptor
      function. Equine MHC class I clone 3.4, which possesses threonine at position
      173, was unable to act as an EHV-1 receptor. Substitution of alanine for
      threonine at position 173 (T173A) enabled MHC class I 3.4 to mediate EHV-1 entry
      into cells. These results suggest that the amino acid residue at position 173 of
      the MHC class I molecule is involved in the efficiency of EHV-1 entry.

PMID- 21949189
TI  - The S100A10-annexin A2 complex provides a novel asymmetric platform for membrane
      repair.
AB  - Membrane repair is mediated by multiprotein complexes, such as that formed
      between the dimeric EF-hand protein S100A10, the calcium- and phospholipid
      binding protein annexin A2, the enlargeosome protein AHNAK, and members of the
      transmembrane ferlin family. Although interactions between these proteins have
      been shown, little is known about their structural arrangement and mechanisms of
      formation. In this work, we used a non-covalent complex between S100A10 and the N
      terminus of annexin A2 (residues 1-15) and a designed hybrid protein (A10A2),
      where S100A10 is linked in tandem to the N-terminal region of annexin A2, to
      explore the binding region, stoichiometry, and affinity with a synthetic peptide
      from the C terminus of AHNAK. Using multiple biophysical methods, we identified a
      novel asymmetric arrangement between a single AHNAK peptide and the A10A2 dimer.
      The AHNAK peptide was shown to require the annexin A2 N terminus, indicating that
      the AHNAK binding site comprises regions on both S100A10 and annexin proteins.
      NMR spectroscopy was used to show that the AHNAK binding surface comprised
      residues from helix IV in S100A10 and the C-terminal portion from the annexin A2
      peptide. This novel surface maps to the exposed side of helices IV and IV' of the
      S100 dimeric structure, a region not identified in any previous S100 target
      protein structures. The results provide the first structural details of the
      ternary S100A10 protein complex required for membrane repair.

PMID- 21949190
TI  - Accuracy of self-reported drinking: observational verification of 'last occasion'
      drink estimates of young adults.
AB  - AIMS: As a formative step towards determining the accuracy of self-reported
      drinking levels commonly used for estimating population alcohol use, the validity
      of a 'last occasion' self-reporting approach is tested with corresponding field
      observations of participants' drinking quantity. This study is the first known
      attempt to validate the accuracy of self-reported alcohol consumption using data
      from a natural setting. METHODS: A total of 81 young adults (aged 18-25 years)
      were purposively selected in Perth, Western Australia. Participants were asked to
      report the number of alcoholic drinks consumed at nightlife venues 1-2 days after
      being observed by peer-based researchers on 239 occasions. Complete observation
      data and self-report estimates were available for 129 sessions, which were fitted
      with multi-level models assessing the relationship between observed and reported
      consumption. RESULTS: Participants accurately estimated their consumption when
      engaging in light to moderate drinking (eight or fewer drinks in a single
      session), with no significant difference between the mean reported consumption
      and the mean observed consumption. In contrast, participants underestimated their
      own consumption by increasing amounts when engaging in heavy drinking of more
      than eight drinks. CONCLUSION: It is suggested that recent recall methods in self
      report surveys are potentially reasonably accurate measures of actual drinking
      levels for light to moderate drinkers, but that underestimating of alcohol
      consumption increases with heavy consumption. Some of the possible reasons for
      underestimation of heavy drinking are discussed, with both cognitive and socio
      cultural factors considered.

PMID- 21949191
TI  - 'For debate': NICE but needy: English guidance on managing alcohol dependence is
      not backed up by government alcohol policy.

PMID- 21949193
TI  - AHVLA outlines its approach to tendering for TB testing.

PMID- 21949194
TI  - Tenders invited to provide veterinary reserve personnel and expert advice.

PMID- 21949192
TI  - Brief alcohol intervention by newly trained workers versus leaflets: comparison
      of effect in older heavy drinkers identified in a population health examination
      survey: a randomized controlled trial.
AB  - AIMS: To test if a brief motivational intervention (BMI) in a non-treatment
      seeking population of heavy drinkers results in a reduced alcohol intake.
      METHODS: Screening of 12,364 participants in a Danish health examination survey
      led to 1026 heavy drinkers of whom 772 were included and randomized to a BMI
      group (n = 391) or a control group (n = 381) receiving two leaflets about
      alcohol. Follow-up took place after 6 and 12 months including 670 and 616
      participants respectively. The outcome measure was self-reported weekly alcohol
      consumption. Data were analysed according to the intention-to-treat principle. We
      used the Motivational Interviewing Treatment Integrity 3.0 code (MITI) as a
      quality control of the interventions delivered. RESULTS: The intervention effect
      of the BMI was -1.0 drinks/week, but the effect was not significant. The MITI
      analysis showed that the quality of the BMI delivered was sub-optimal, as only
      one of four aspects was above the recommended level for beginning proficiency.
      CONCLUSION: We found no effect of a BMI in reducing alcohol consumption. The
      generalizability of the study is questionable, as individuals with the lowest
      level of education, low income and unmarried individuals are under-represented.

PMID- 21949196
TI  - AHVLA plans more use of paraprofessionals.

PMID- 21949199
TI  - BVA renews call for compulsory microchipping.

PMID- 21949200
TI  - From bovine TB to changes to the pet travel rules.

PMID- 21949201
TI  - Funding to boost dairy farmers' skills.

PMID- 21949202
TI  - Neoliberal reform and the veterinary profession.

PMID- 21949203
TI  - Testing for CEMO, Klebsiella pneumoniae and Pseudomonas aeruginosa.

PMID- 21949204
TI  - Reducing surgical complications.

PMID- 21949205
TI  - Preventing dog bite injuries: the need for a collaborative approach.

PMID- 21949206
TI  - Dissolution of the South Wales Division of the BVA (SWBVA).

PMID- 21949207
TI  - Survey of farm animal practice business models.

PMID- 21949208
TI  - Welfare and quality assurance schemes.

PMID- 21949209
TI  - Tyrosine aminotransferase contributes to benzylisoquinoline alkaloid biosynthesis
      in opium poppy.
AB  - Tyrosine aminotransferase (TyrAT) catalyzes the transamination of L-Tyr and alpha
      ketoglutarate, yielding 4-hydroxyphenylpyruvic acid and L-glutamate. The
      decarboxylation product of 4-hydroxyphenylpyruvic acid, 4
      hydroxyphenylacetaldehyde, is a precursor to a large and diverse group of natural
      products known collectively as benzylisoquinoline alkaloids (BIAs). We have
      isolated and characterized a TyrAT cDNA from opium poppy (Papaver somniferum),
      which remains the only commercial source for several pharmaceutical BIAs,
      including codeine, morphine, and noscapine. TyrAT belongs to group I pyridoxal 5'
      phosphate (PLP)-dependent enzymes wherein Schiff base formation occurs between
      PLP and a specific Lys residue. The amino acid sequence of TyrAT showed
      considerable homology to other putative plant TyrATs, although few of these have
      been functionally characterized. Purified, recombinant TyrAT displayed a
      molecular mass of approximately 46 kD and a substrate preference for L-Tyr and
      alpha-ketoglutarate, with apparent K(m) values of 1.82 and 0.35 mm, respectively.
      No specific requirement for PLP was detected in vitro. Liquid chromatography
      tandem mass spectrometry confirmed the conversion of L-Tyr to 4
      hydroxyphenylpyruvate. TyrAT gene transcripts were most abundant in roots and
      stems of mature opium poppy plants. Virus-induced gene silencing was used to
      evaluate the contribution of TyrAT to BIA metabolism in opium poppy. TyrAT
      transcript levels were reduced by at least 80% in silenced plants compared with
      controls and showed a moderate reduction in total alkaloid content. The modest
      correlation between transcript levels and BIA accumulation in opium poppy
      supports a role for TyrAT in the generation of alkaloid precursors, but it also
      suggests the occurrence of other sources for 4-hydroxyphenylacetaldehyde.

PMID- 21949210
TI  - The glossyhead1 allele of ACC1 reveals a principal role for multidomain acetyl
      coenzyme A carboxylase in the biosynthesis of cuticular waxes by Arabidopsis.
AB  - A novel mutant of Arabidopsis (Arabidopsis thaliana), having highly glossy
      inflorescence stems, postgenital fusion in floral organs, and reduced fertility,
      was isolated from an ethyl methanesulfonate-mutagenized population and designated
      glossyhead1 (gsd1). The gsd1 locus was mapped to chromosome 1, and the causal
      gene was identified as a new allele of Acetyl-Coenzyme A Carboxylase1 (ACC1), a
      gene encoding the main enzyme in cytosolic malonyl-coenzyme A synthesis. This, to
      our knowledge, is the first mutant allele of ACC1 that does not cause lethality
      at the seed or early germination stage, allowing for the first time a detailed
      analysis of ACC1 function in mature tissues. Broad lipid profiling of mature gsd1
      organs revealed a primary role for ACC1 in the biosynthesis of the very-long
      chain fatty acids (C(20:0) or longer) associated with cuticular waxes and
      triacylglycerols. Unexpectedly, transcriptome analysis revealed that gsd1 has
      limited impact on any lipid metabolic networks but instead has a large effect on
      environmental stress-responsive pathways, especially senescence and ethylene
      synthesis determinants, indicating a possible role for the cytosolic malonyl
      coenzyme A-derived lipids in stress response signaling.

PMID- 21949211
TI  - Identification of essential subunits in the plastid-encoded RNA polymerase
      complex reveals building blocks for proper plastid development.
AB  - The major RNA polymerase activity in mature chloroplasts is a multisubunit,
      Escherichia coli-like protein complex called PEP (for plastid-encoded RNA
      polymerase). Its subunit structure has been extensively investigated by
      biochemical means. Beside the "prokaryotic" subunits encoded by the plastome
      located RNA polymerase genes, a number of additional nucleus-encoded subunits of
      eukaryotic origin have been identified in the PEP complex. These subunits appear
      to provide additional functions and regulation modes necessary to adapt
      transcription to the varying functional situations in chloroplasts. However,
      despite the enormous progress in genomic data and mass spectrometry techniques,
      it is still under debate which of these subunits belong to the core complex of
      PEP and which ones represent rather transient or peripheral components. Here, we
      present a catalog of true PEP subunits that is based on comparative analyses from
      biochemical purifications, protein mass spectrometry, and phenotypic analyses. We
      regard reproducibly identified protein subunits of the basic PEP complex as
      essential when the corresponding knockout mutants reveal an albino or pale-green
      phenotype. Our study provides a clearly defined subunit catalog of the basic PEP
      complex, generating the basis for a better understanding of chloroplast
      transcription regulation. In addition, the data support a model that links PEP
      complex assembly and chloroplast buildup during early seedling development in
      vascular plants.

PMID- 21949212
TI  - Dissecting the role of CHITINASE-LIKE1 in nitrate-dependent changes in root
      architecture.
AB  - The root phenotype of an Arabidopsis (Arabidopsis thaliana) mutant of CHITINASE
      LIKE1 (CTL1), called arm (for anion-related root morphology), was previously
      shown to be conditional on growth on high nitrate, chloride, or sucrose. Mutants
      grown under restrictive conditions displayed inhibition of primary root growth,
      radial swelling, proliferation of lateral roots, and increased root hair density.
      We found here that the spatial pattern of CTL1 expression was mainly in the root
      and root tips during seedling development and that the protein localized to the
      cell wall. Fourier-transform infrared microspectroscopy of mutant root tissues
      indicated differences in spectra assigned to linkages in cellulose and pectin.
      Indeed, root cell wall polymer composition analysis revealed that the arm mutant
      contained less crystalline cellulose and reduced methylesterification of pectins.
      We also explored the implication of growth regulators on the phenotype of the
      mutant response to the nitrate supply. Exogenous abscisic acid application
      inhibited more drastically primary root growth in the arm mutant but failed to
      repress lateral branching compared with the wild type. Cytokinin levels were
      higher in the arm root, but there were no changes in mitotic activity, suggesting
      that cytokinin is not directly involved in the mutant phenotype. Ethylene
      production was higher in arm but inversely proportional to the nitrate
      concentration in the medium. Interestingly, eto2 and eto3 ethylene overproduction
      mutants mimicked some of the conditional root characteristics of the arm mutant
      on high nitrate. Our data suggest that ethylene may be involved in the arm mutant
      phenotype, albeit indirectly, rather than functioning as a primary signal.

PMID- 21949213
TI  - Toward the storage metabolome: profiling the barley vacuole.
AB  - While recent years have witnessed dramatic advances in our capacity to identify
      and quantify an ever-increasing number of plant metabolites, our understanding of
      how metabolism is spatially regulated is still far from complete. In an attempt
      to partially address this question, we studied the storage metabolome of the
      barley (Hordeum vulgare) vacuole. For this purpose, we used highly purified
      vacuoles isolated by silicon oil centrifugation and compared their metabolome
      with that found in the mesophyll protoplast from which they were derived. Using a
      combination of gas chromatography-mass spectrometry and Fourier transform-mass
      spectrometry, we were able to detect 59 (primary) metabolites for which we know
      the exact chemical structure and a further 200 (secondary) metabolites for which
      we have strong predicted chemical formulae. Taken together, these metabolites
      comprise amino acids, organic acids, sugars, sugar alcohols, shikimate pathway
      intermediates, vitamins, phenylpropanoids, and flavonoids. Of the 259 putative
      metabolites, some 12 were found exclusively in the vacuole and 34 were found
      exclusively in the protoplast, while 213 were common in both samples. When
      analyzed on a quantitative basis, however, there is even more variance, with more
      than 60 of these compounds being present above the detection limit of our
      protocols. The combined data were also analyzed with respect to the tonoplast
      proteome in an attempt to infer specificities of the transporter proteins
      embedded in this membrane. Following comparison with recent observations made
      using nonaqueous fractionation of Arabidopsis (Arabidopsis thaliana), we discuss
      these data in the context of current models of metabolic compartmentation in
      plants.

PMID- 21949215
TI  - Toward more accurate pan-specific MHC-peptide binding prediction: a review of
      current methods and tools.
AB  - Binding of short antigenic peptides to major histocompatibility complex (MHC)
      molecules is a core step in adaptive immune response. Precise identification of
      MHC-restricted peptides is of great significance for understanding the mechanism
      of immune response and promoting the discovery of immunogenic epitopes. However,
      due to the extremely high MHC polymorphism and huge cost of biochemical
      experiments, there is no experimentally measured binding data for most MHC
      molecules. To address the problem of predicting peptides binding to these MHC
      molecules, recently computational approaches, called pan-specific methods, have
      received keen interest. Pan-specific methods make use of experimentally obtained
      binding data of multiple alleles, by which binding peptides (binders) of not only
      these alleles but also those alleles with no known binders can be predicted. To
      investigate the possibility of further improvement in performance and usability
      of pan-specific methods, this article extensively reviews existing pan-specific
      methods and their web servers. We first present a general framework of pan
      specific methods. Then, the strategies and performance as well as utilities of
      web servers are compared. Finally, we discuss the future direction to improve pan
      specific methods for MHC-peptide binding prediction.

PMID- 21949214
TI  - Dynamics of the plant nuclear envelope and nuclear pore.

PMID- 21949217
TI  - The relationship between rational drug design and drug side effects.
AB  - Previous analysis of systems pharmacology has revealed a tendency of rational
      drug design in the pharmaceutical industry. The targets of new drugs tend to be
      close with the corresponding disease genes in the biological networks. However,
      it remains unclear whether the rational drug design introduces disadvantages,
      i.e. side effects. Therefore, it is important to dissect the relationship between
      rational drug design and drug side effects. Based on a recently released drug
      side effect database, SIDER, here we analyzed the relationship between drug side
      effects and the rational drug design. We revealed that the incidence drug side
      effect is significantly associated with the network distance of drug targets and
      diseases genes. Drugs with the distances of three or four have the smallest
      incidence of side effects, whereas drugs with the distances of more than four or
      smaller than three show significantly greater incidence of side effects.
      Furthermore, protein drugs and small molecule drugs show significant differences.
      Drugs hitting membrane targets and drugs hitting cytoplasm targets also show
      differences. Failure drugs because of severe side effects show smaller network
      distances than approved drugs. These results suggest that researchers should be
      prudent on rationalizing the drug design. Too small distances between drug
      targets and diseases genes may not always be advantageous for rational design for
      drug discovery.

PMID- 21949216
TI  - Lessons from a decade of integrating cancer copy number alterations with gene
      expression profiles.
AB  - Over the last decade, multiple functional genomic datasets studying chromosomal
      aberrations and their downstream effects on gene expression have accumulated for
      several cancer types. A vast majority of them are in the form of paired gene
      expression profiles and somatic copy number alterations (CNA) information on the
      same patients identified using microarray platforms. In response, many algorithms
      and software packages are available for integrating these paired data.
      Surprisingly, there has been no serious attempt to review the currently available
      methodologies or the novel insights brought using them. In this work, we discuss
      the quantitative relationships observed between CNA and gene expression in
      multiple cancer types and biological milestones achieved using the available
      methodologies. We discuss the conceptual evolution of both, the step-wise and the
      joint data integration methodologies over the last decade. We conclude by
      providing suggestions for building efficient data integration methodologies and
      asking further biological questions.

PMID- 21949218
TI  - Pretransplant risk score for new-onset diabetes after kidney transplantation.
AB  - OBJECTIVE: New-onset diabetes after kidney transplantation (NODAT) has adverse
      clinical and economic implications. A risk score for NODAT could help identify
      research subjects for intervention studies. RESEARCH DESIGN AND METHODS: We
      conducted a single-center retrospective cohort study using pretransplant clinical
      and laboratory measurements to construct a risk score for NODAT. NODAT was
      defined by hemoglobin A(1c) (HbA(1c)) >=6.5%, fasting serum glucose >=126 mg/dL,
      or prescribed therapy for diabetes within 1 year posttransplant. Three
      multivariate logistic regression models were constructed: 1) standard model, with
      both continuous and discrete variables; 2) dichotomous model, with continuous
      variables dichotomized at clinically relevant cut points; and 3) summary score
      defined as the sum of the points accrued using the terms from the dichotomous
      model. RESULTS: A total of 316 subjects had seven pretransplant variables with P
      < 0.10 in univariate logistic regression analyses (age, planned corticosteroid
      therapy posttransplant, prescription for gout medicine, BMI, fasting glucose and
      triglycerides, and family history of type 2 diabetes) that were selected for
      multivariate models. Areas under receiver operating curves for all three models
      were similar (0.72, 0.71, and 0.70). A simple risk score calculated as the sum of
      points from the seven variables performed as well as the other two models in
      identifying risk of NODAT. CONCLUSIONS: A risk score computed from seven simple
      pretransplant variables can identify risk of NODAT.

PMID- 21949219
TI  - Improving the estimation of mealtime insulin dose in adults with type 1 diabetes:
      the Normal Insulin Demand for Dose Adjustment (NIDDA) study.
AB  - OBJECTIVE: Although carbohydrate counting is routine practice in type 1 diabetes,
      hyperglycemic episodes are common. A food insulin index (FII) has been developed
      and validated for predicting the normal insulin demand generated by mixed meals
      in healthy adults. We sought to compare a novel algorithm on the basis of the FII
      for estimating mealtime insulin dose with carbohydrate counting in adults with
      type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 28 patients using
      insulin pump therapy consumed two different breakfast meals of equal energy,
      glycemic index, fiber, and calculated insulin demand (both FII = 60) but
      approximately twofold difference in carbohydrate content, in random order on
      three consecutive mornings. On one occasion, a carbohydrate-counting algorithm
      was applied to meal A (75 g carbohydrate) for determining bolus insulin dose. On
      the other two occasions, carbohydrate counting (about half the insulin dose as
      meal A) and the FII algorithm (same dose as meal A) were applied to meal B (41 g
      carbohydrate). A real-time continuous glucose monitor was used to assess 3-h
      postprandial glycemia. RESULTS: Compared with carbohydrate counting, the FII
      algorithm significantly decreased glucose incremental area under the curve over 3
      h (-52%, P = 0.013) and peak glucose excursion (-41%, P = 0.01) and improved the
      percentage of time within the normal blood glucose range (4-10 mmol/L) (31%, P =
      0.001). There was no significant difference in the occurrence of hypoglycemia.
      CONCLUSIONS: An insulin algorithm based on physiological insulin demand evoked by
      foods in healthy subjects may be a useful tool for estimating mealtime insulin
      dose in patients with type 1 diabetes.

PMID- 21949220
TI  - Decreases in diabetes-free life expectancy in the U.S. and the role of obesity.
AB  - OBJECTIVE: With increasing life expectancy in the U.S., it is important to know
      whether a longer life expectancy means a longer healthy life span or a prolonged
      period of later-life morbidity. This study examines changes in lifetime without
      diabetes, a leading cause of morbidity in later life. RESEARCH DESIGN AND
      METHODS: Using demographic methods and nationally representative data, we
      estimated changes in diabetes-free life expectancy between 1980-1989 and 2000
      2004 for adult men and women in the U.S., estimated the contribution of changes
      in age-specific diabetes rates, and examined the changing effects of weight
      status on diabetes risks. RESULTS: While life expectancy at age 18 for men and
      women increased between the 1980s and the 2000s, diabetes-free life expectancy at
      age 18 decreased by 1.7 years for men and 1.5 years for women. The proportion of
      18-year-olds who would develop diabetes in their lifetimes increased by almost
      50% among women and almost doubled among men. Obese individuals experienced the
      greatest losses in diabetes-free life expectancy during this period, estimated at
      5.6 years for men and 2.5 years for women. CONCLUSIONS: Diabetes-free life
      expectancy decreased for both men and women between 1980-1989 and 2000-2004, and
      these decreases are almost entirely attributable to large increases in diabetes
      incidence among obese individuals.

PMID- 21949221
TI  - Postprandial blood glucose predicts cardiovascular events and all-cause mortality
      in type 2 diabetes in a 14-year follow-up: lessons from the San Luigi Gonzaga
      Diabetes Study.
AB  - OBJECTIVE: To evaluate whether postprandial blood glucose predicts cardiovascular
      events and all-cause mortality in type 2 diabetes in a long-term follow-up taking
      into account A1C and the main cardiovascular risk factors. RESEARCH DESIGN AND
      METHODS: Consecutive type 2 diabetic patients (n = 505) followed up at our
      diabetes clinic were evaluated at baseline (1995) for the main cardiovascular
      risk factors and for five glycemic control parameters (fasting blood glucose,
      blood glucose 2 h after breakfast, blood glucose 2 h after lunch, blood glucose
      before dinner, and A1C); all-cause mortality and the first cardiovascular events
      occurring during the 14-year follow-up were measured. RESULTS: We observed 172
      cardiovascular events (34.1% of the population) and 147 deaths (29.1% of the
      population). Using the Cox analysis with the backward method, we categorized the
      variables according to the therapeutic targets of the American Diabetes
      Association. Our observations were as follows. When the five glycemic control
      parameters were considered together, the predictors were 1) for cardiovascular
      events, blood glucose 2 h after lunch (hazard ratio 1.507, P = 0.010) and A1C
      (1.792, P = 0.002); and 2) for mortality, blood glucose 2 h after lunch (1.885, P
      < 0.0001) and A1C (1.907, P = 0.002). When blood glucose 2 h after lunch and A1C
      were considered together with the main cardiovascular risk factors, the following
      glycemic control parameters were predictors: 1) for cardiovascular events, blood
      glucose 2 h after lunch (1.452, P = 0.021) and A1C (1.732, P = 0.004); and 2) for
      mortality, blood glucose 2 h after lunch (1.846, P = 0.001) and A1C (1.896, P =
      0.004). CONCLUSIONS: In type 2 diabetes, both postprandial blood glucose and A1C
      predict cardiovascular events and all-cause mortality in a long-term follow-up.

PMID- 21949222
TI  - Metformin in gestational diabetes: the offspring follow-up (MiG TOFU): body
      composition at 2 years of age.
AB  - OBJECTIVE: In women with gestational diabetes mellitus, who were randomized to
      metformin or insulin treatment, pregnancy outcomes were similar (Metformin in
      Gestational diabetes [MiG] trial). Metformin crosses the placenta, so it is
      important to assess potential effects on growth of the children. RESEARCH DESIGN
      AND METHODS: In Auckland, New Zealand, and Adelaide, Australia, women who had
      participated in the MiG trial were reviewed when their children were 2 years old.
      Body composition was measured in 154 and 164 children whose mothers had been
      randomized to metformin and insulin, respectively. Children were assessed with
      anthropometry, bioimpedance, and dual energy X-ray absorptiometry (DEXA), using
      standard methods. RESULTS: The children were similar for baseline maternal
      characteristics and pregnancy outcomes. In the metformin group, compared with the
      insulin group, children had larger mid-upper arm circumferences (17.2 +/- 1.5 vs.
      16.7 +/- 1.5 cm; P = 0.002) and subscapular (6.3 +/- 1.9 vs. 6.0 +/- 1.7 mm; P =
      0.02) and biceps skinfolds (6.03 +/- 1.9 vs. 5.6 +/- 1.7 mm; P = 0.04). Total fat
      mass and percentage body fat assessed by bioimpedance (n = 221) and DEXA (n =
      114) were not different. CONCLUSIONS: Children exposed to metformin had larger
      measures of subcutaneous fat, but overall body fat was the same as in children
      whose mothers were treated with insulin alone. Further follow-up is required to
      examine whether these findings persist into later life and whether children
      exposed to metformin will develop less visceral fat and be more insulin
      sensitive. If so, this would have significant implications for the current
      pandemic of diabetes.

PMID- 21949223
TI  - Reduced risk of colorectal cancer with metformin therapy in patients with type 2
      diabetes: a meta-analysis.
AB  - OBJECTIVE: Both in vitro and in vivo studies indicate that metformin inhibits
      cancer cell growth and reduces cancer risk. Recent epidemiological studies
      suggest that metformin therapy may reduce the risks of cancer and overall cancer
      mortality among patients with type 2 diabetes. However, data on its effect on
      colorectal cancer are limited and inconsistent. We therefore pooled data
      currently available to examine the association between metformin therapy and
      colorectal cancer among patients with type 2 diabetes. RESEARCH DESIGN AND
      METHODS: The PubMed and SciVerse Scopus databases were searched to identify
      studies that examined the effect of metformin therapy on colorectal cancer among
      patients with type 2 diabetes. Summary effect estimates were derived using a
      random-effects meta-analysis model. RESULTS: The analysis included five studies
      comprising 108,161 patients with type 2 diabetes. Metformin treatment was
      associated with a significantly lower risk of colorectal neoplasm (relative risk
      [RR] 0.63 [95% CI 0.50-0.79]; P < 0.001). After exclusion of one study that
      investigated colorectal adenoma, the remaining four studies comprised 107,961
      diabetic patients and 589 incident colorectal cancer cases during follow-up.
      Metformin treatment was associated with a significantly lower risk of colorectal
      cancer (0.63 [0.47-0.84]; P = 0.002). There was no evidence for the presence of
      significant heterogeneity between the five studies (Q = 4.86, P = 0.30; I(2) =
      18%). CONCLUSIONS: From observational studies, metformin therapy appears to be
      associated with a significantly lower risk of colorectal cancer in patients with
      type 2 diabetes. Further investigation is warranted.

PMID- 21949224
TI  - Metformin therapy during pregnancy: good for the goose and good for the gosling
      too?

PMID- 21949225
TI  - Aiming at new targets to achieve normoglycemia during pregnancy.

PMID- 21949226
TI  - Postprandial glucose: marker or risk factor?

PMID- 21949227
TI  - Metformin and colorectal cancer risk in diabetic patients.

PMID- 21949229
TI  - World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease: part
      4.

PMID- 21949230
TI  - Inhibition of IL-1beta improves fatigue in type 2 diabetes.

PMID- 21949231
TI  - Diabetic foot ulcer: amputation on request?

PMID- 21949232
TI  - Comment on: Lipsky et al. Developing and validating a risk score for lower
      extremity amputation in patients hospitalized for a diabetic foot infection.
      Diabetes Care 2011;34:1695-1700.

PMID- 21949234
TI  - Comment on: Rogers et al. Blood pressure trajectories prior to death in patients
      with diabetes. Diabetes Care 2011;34:1534-1539.

PMID- 21949236
TI  - The expression profile of de-N-acetyl polysialic acid (NeuPSA) in normal and
      diseased human tissue.
AB  - Although sialic acids have a key role in many aspects of human biology, the
      expression of polysialic acid (PSA) in human tissues is thought to be relatively
      rare. We identified a derivative of PSA called neuraminic acid-containing PSA or
      NeuPSA that was highly expressed in primary human melanoma tumors and in several
      cancer cell lines. Moreover, anti-NeuPSA antibodies could induce apoptosis of
      cancer cells. However, little was known about NeuPSA expression in normal or
      diseased tissues. In this study we investigated the complete expression profile
      of NeuPSA in human tissues and a few primary tumors using the anti-NeuPSA
      monoclonal antibody, SEAM 3. Almost every human tissue tested spanning a
      representative sample of all organ types was positive for SEAM 3 binding.
      Specificity of SEAM 3 binding was established by inhibition with NeuPSA but not
      closely related meningococcal C polysaccharide and loss of SEAM 3 binding when
      specimens were treated with periodate at high pH, which specifically destroys
      NeuPSA. Only subsets of cells in each specimen stained positive, and the relative
      staining between tissues was variable. The distribution and amount of NeuPSA
      antigen in tissues was correlated with known levels of polysialyltransferase PST
      or STX expression. The majority of anti-NeuPSA binding occurred intracellularly
      in the cytoplasm of cells. Tumors generally exhibited considerably increased
      staining compared with corresponding normal tissues. Identifying the diverse
      tissue distribution and intracellular location of NeuPSA provides a foundation
      for investigating the functional role of NeuPSA in human health and disease.

PMID- 21949237
TI  - Phosphomannose isomerase inhibitors improve N-glycosylation in selected
      phosphomannomutase-deficient fibroblasts.
AB  - Congenital disorders of glycosylation (CDG) are rare genetic disorders due to
      impaired glycosylation. The patients with subtypes CDG-Ia and CDG-Ib have
      mutations in the genes encoding phosphomannomutase 2 (PMM2) and phosphomannose
      isomerase (MPI or PMI), respectively. PMM2 (mannose 6-phosphate -> mannose 1
      phosphate) and MPI (mannose 6-phosphate <=> fructose 6-phosphate) deficiencies
      reduce the metabolic flux of mannose 6-phosphate (Man-6-P) into glycosylation,
      resulting in unoccupied N-glycosylation sites. Both PMM2 and MPI compete for the
      same substrate, Man-6-P. Daily mannose doses reverse most of the symptoms of MPI
      deficient CDG-Ib patients. However, CDG-Ia patients do not benefit from mannose
      supplementation because >95% Man-6-P is catabolized by MPI. We hypothesized that
      inhibiting MPI enzymatic activity would provide more Man-6-P for glycosylation
      and possibly benefit CDG-Ia patients with residual PMM2 activity. Here we show
      that MLS0315771, a potent MPI inhibitor from the benzoisothiazolone series,
      diverts Man-6-P toward glycosylation in various cell lines including fibroblasts
      from CDG-Ia patients and improves N-glycosylation. Finally, we show that
      MLS0315771 increases mannose metabolic flux toward glycosylation in zebrafish
      embryos.

PMID- 21949238
TI  - Binding to syntenin-1 protein defines a new mode of ubiquitin-based interactions
      regulated by phosphorylation.
AB  - Syntenin-1 is a PDZ domain-containing adaptor that controls trafficking of
      transmembrane proteins including those associated with tetraspanin-enriched
      microdomains. We describe the interaction of syntenin-1 with ubiquitin through a
      novel binding site spanning the C terminus of ubiquitin, centered on Arg(72),
      Leu(73), and Arg(74). A conserved LYPSL sequence in the N terminus, as well as
      the C-terminal region of syntenin-1, are essential for binding to ubiquitin. We
      present evidence for the regulation of this interaction through syntenin-1
      dimerization. We have also established that syntenin-1 is phosphorylated
      downstream of Ulk1, a serine/threonine kinase that plays a critical role in
      autophagy and regulates endocytic trafficking. Importantly, Ulk1-dependent
      phosphorylation of Ser(6) in the LYPSL prevents the interaction of syntenin-1
      with ubiquitin. These results define an unprecedented ubiquitin-dependent pathway
      involving syntenin-1 that is regulated by Ulk1.

PMID- 21949241
TI  - Detecting coevolving positions in a molecule: why and how to account for
      phylogeny.
AB  - Positions in a molecule that share a common constraint do not evolve
      independently, and therefore leave a signature in the patterns of homologous
      sequences. Exhibiting such positions with a coevolution pattern from a sequence
      alignment has great potential for predicting functional and structural properties
      of molecules through comparative analysis. This task is complicated by the
      existence of additional correlation sources, leading to false predictions. The
      nature of the data is a major source of noise correlation: sequences are taken
      from individuals with different degrees of relatedness, and who therefore are
      intrinsically correlated. This has led to several method developments in
      different fields that are potentially confusing for non-expert users interested
      in these methodologies. It also explains why coevolution detection methods are
      largely unemployed despite the importance of the biological questions they
      address. In this article, I focus on the role of shared ancestry for
      understanding molecular coevolution patterns. I review and classify existing
      coevolution detection methods according to their ability to handle shared
      ancestry. Using a ribosomal RNA benchmark data set, for which detailed knowledge
      of the structure and coevolution patterns is available, I demonstrate and explain
      why taking the underlying evolutionary history of sequences into account is the
      only way to extract the full coevolution signal in the data. I also evaluate,
      using rigorous statistical procedures, the best approaches to do so, and discuss
      several important biological aspects to consider when performing coevolution
      analyses.

PMID- 21949239
TI  - Myotonic dystrophy protein kinase is critical for nuclear envelope integrity.
AB  - Myotonic dystrophy 1 (DM1) is a multisystemic disease caused by a triplet
      nucleotide repeat expansion in the 3' untranslated region of the gene coding for
      myotonic dystrophy protein kinase (DMPK). DMPK is a nuclear envelope (NE) protein
      that promotes myogenic gene expression in skeletal myoblasts. Muscular dystrophy
      research has revealed the NE to be a key determinant of nuclear structure, gene
      regulation, and muscle function. To investigate the role of DMPK in NE stability,
      we analyzed DMPK expression in epithelial and myoblast cells. We found that DMPK
      localizes to the NE and coimmunoprecipitates with Lamin-A/C. Overexpression of
      DMPK in HeLa cells or C2C12 myoblasts disrupts Lamin-A/C and Lamin-B1
      localization and causes nuclear fragmentation. Depletion of DMPK also disrupts NE
      lamina, showing that DMPK is required for NE stability. Our data demonstrate for
      the first time that DMPK is a critical component of the NE. These novel findings
      suggest that reduced DMPK may contribute to NE instability, a common mechanism of
      skeletal muscle wasting in muscular dystrophies.

PMID- 21949242
TI  - What sustains long-term adherence to structured physical activity after a cardiac
      event?
AB  - PURPOSE: Research addressing methods to sustain long-term adherence to physical
      activity among older adults is needed. This study investigated the motivations
      and supports deemed necessary to adhere to a community-based cardiac
      rehabilitation (CBCR) program by individuals with established coronary heart
      disease. METHODS: Twenty-four long-term adherers (15 men, 9 women; age 67.7 +/-
      16.7 yr) took part in focus-group discussions. RESULTS: Constant comparative
      analysis supported previous research in terms of the importance of referral
      procedures, social support, and knowledge of health benefits in influencing
      uptake and adherence to CBCR. Results also highlighted the routine of a
      structured class and task-, barrier-, and recovery-specific self-efficacy as
      necessary to sustain long-term adherence for this specific clinical group.
      DISCUSSION: Older adults themselves provide rich information on how to
      successfully support their long-term adherence to structured exercise sessions.
      Further research into how to build these components into any exercise program is
      necessary.

PMID- 21949243
TI  - Improvements in functional capacity from Nordic walking: a randomized-controlled
      trial among elderly people.
AB  - This study examined the effects of an instructed structured Nordic walking (NW)
      exercise program on the functional capacity of older sedentary people. Volunteers
      were randomly assigned to an NW group (68.2 +/- 3.8 yr old) or control group
      (69.9 +/- 3.0 yr old). Before and at the end of the 9-wk intervention, functional
      tests and 2-dimensional ground-reaction-force (GRF) patterns of normal (1.40 m/s)
      and fast (1.94 m/s) walking speeds were measured. The intervention included a 60
      min supervised NW session on an inside track twice a week for 9 wk. The mean
      changes in functional tests differed between groups significantly. Gait analyses
      showed no significant differences between the groups on any GRF parameters for
      walking speed either before or after the intervention. The study showed that NW
      has favorable effects on functional capacity in older people and is a suitable
      form of exercise for them.

PMID- 21949244
TI  - Development of a highly sensitive method using liquid chromatography-multiple
      reaction monitoring to quantify membrane P-glycoprotein in biological matrices
      and relationship to transport function.
AB  - The quantification of P-glycoprotein [P-gp, ABCB1, multidrug resistance 1 (MDR1)]
      protein in biological matrices is considered a key factor missing for useful
      translation of in vitro functional data to the in vivo situation and for
      comparison of transporter data among different in vitro models. In the present
      study a liquid chromatography (LC)-mass spectrometry method was developed to
      quantify P-gp membrane protein levels in different biological matrices. The
      amount of P-gp transporter protein was measured in Caco-2 cell monolayers and in
      inside-out human embryonic kidney (HEK)-MDR1 vesicles. From both in vitro
      systems, two preparations with different functionality were used. Transporter
      function was determined as digoxin efflux in Caco-2 cell monolayers and N
      methylquinidine (NMQ) uptake in membrane vesicles, and, in addition, mRNA
      expression in the Caco-2 monolayers was measured. The results showed an excellent
      relationship between NMQ uptake functionality in inside-out HEK-MDR1 vesicles and
      protein contents. Similar concordance between the digoxin efflux and P-gp content
      in different Caco-2 cell cultures was observed, whereas mRNA levels are
      indicative of increased P-gp content and activity in older Caco-2 cultures,
      however, not yielding the same quantitative relationship. The results from both
      Caco-2 and HEK-MDR1 membrane vesicles confirm that the protein content is
      directly related to the level of activity in the respective system. The method
      presented here to quantify P-gp protein by LC-multiple reaction monitoring will
      facilitate the development of future methodologies to bridge between expression
      systems and cell/tissue models and to scale from in vitro models to whole organs.

PMID- 21949245
TI  - Molecular basis for amyloid-beta polymorphism.
AB  - Amyloid-beta (Abeta) aggregates are the main constituent of senile plaques, the
      histological hallmark of Alzheimer's disease. Abeta molecules form beta-sheet
      containing structures that assemble into a variety of polymorphic oligomers,
      protofibers, and fibers that exhibit a range of lifetimes and cellular
      toxicities. This polymorphic nature of Abeta has frustrated its biophysical
      characterization, its structural determination, and our understanding of its
      pathological mechanism. To elucidate Abeta polymorphism in atomic detail, we
      determined eight new microcrystal structures of fiber-forming segments of Abeta.
      These structures, all of short, self-complementing pairs of beta-sheets termed
      steric zippers, reveal a variety of modes of self-association of Abeta. Combining
      these atomic structures with previous NMR studies allows us to propose several
      fiber models, offering molecular models for some of the repertoire of
      polydisperse structures accessible to Abeta. These structures and molecular
      models contribute fundamental information for understanding Abeta polymorphic
      nature and pathogenesis.

PMID- 21949247
TI  - Maintenance of adenomatous polyposis coli (APC)-mutant colorectal cancer is
      dependent on Wnt/beta-catenin signaling.
AB  - Persistent expression of certain oncogenes is required for tumor maintenance.
      This phenotype is referred to as oncogene addiction and has been clinically
      validated by anticancer therapies that specifically inhibit oncoproteins such as
      BCR-ABL, c-Kit, HER2, PDGFR, and EGFR. Identifying additional genes that are
      required for tumor maintenance may lead to new targets for anticancer drugs.
      Although the role of aberrant Wnt pathway activation in the initiation of
      colorectal cancer has been clearly established, it remains unclear whether
      sustained Wnt pathway activation is required for colorectal tumor maintenance. To
      address this question, we used inducible beta-catenin shRNAs to temporally
      control Wnt pathway activation in vivo. Here, we show that active Wnt/beta
      catenin signaling is required for maintenance of colorectal tumor xenografts
      harboring APC mutations. Reduced tumor growth upon beta-catenin inhibition was
      due to cell cycle arrest and differentiation. Upon reactivation of the Wnt/beta
      catenin pathway colorectal cancer cells resumed proliferation and reacquired a
      crypt progenitor phenotype. In human colonic adenocarcinomas, high levels of
      nuclear beta-catenin correlated with crypt progenitor but not differentiation
      markers, suggesting that the Wnt/beta-catenin pathway may also control colorectal
      tumor cell fate during the maintenance phase of tumors in patients. These results
      support efforts to treat human colorectal cancer by pharmacological inhibition of
      the Wnt/beta-catenin pathway.

PMID- 21949249
TI  - The TRAF-associated protein TANK facilitates cross-talk within the IkappaB kinase
      family during Toll-like receptor signaling.
AB  - Toll-like receptor (TLR) ligands that signal via TIR-domain-containing adapter
      inducing IFNbeta (TRIF) activate the IkappaB kinase (IKK)-related kinases, TRAF
      associated NFkappaB activator (TANK)-binding kinase-1 (TBK1) and IKKepsilon,
      which then phosphorylate IRF3 and induce the production of IFNbeta. Here we show
      that TBK1 and IKKepsilon are also activated by TLR ligands that signal via MyD88.
      Notably, the activation of IKKepsilon is rapid, transient, and it precedes a more
      prolonged activation of TBK1. The MyD88- and TRIF-dependent signaling pathways
      activate the IKK-related kinases by two signaling pathways. One is mediated by
      the canonical IKKs, whereas the other culminates in the autoactivation of the IKK
      related kinases. Once activated, TBK1/IKKepsilon then phosphorylate and inhibit
      the canonical IKKs. The negative regulation of the canonical IKKs by the IKK
      related kinases occurs in both the TRIF- and MyD88-dependent TLR pathways,
      whereas IRF3 phosphorylation is restricted to the TRIF-dependent signaling
      pathway. We have discovered that the activation of IKKepsilon is abolished, the
      activation of TBK1 is reduced, and the interaction between the IKK-related
      kinases and the canonical IKKs is suppressed in TANK(-/-) macrophages, preventing
      the IKK-related kinases from negatively regulating the canonical IKKs. In
      contrast, IRF3 phosphorylation and IFNbeta production was normal in TANK(-/-)
      macrophages. Our results demonstrate a key role for TANK in enabling the
      canonical IKKs and the IKK-related kinases to regulate each other, which is
      required to limit the strength of TLR signaling and ultimately, prevent
      autoimmunity.

PMID- 21949251
TI  - Soluble membrane trafficking proteins taking a break at silent synaptic vesicles.

PMID- 21949252
TI  - No increased risk of caesarean or instrumental delivery for nulliparous women who
      have epidural analgesia early in (term) labour.

PMID- 21949250
TI  - A molecular switch that governs mitochondrial fusion and fission mediated by the
      BCL2-like protein CED-9 of Caenorhabditis elegans.
AB  - Depending on the cellular context, BCL2-like proteins promote mitochondrial
      fusion or fission. What determines which of these two opposing processes they
      promote has so far been unknown. Furthermore, the mechanisms through which BCL2
      like proteins affect mitochondrial dynamics remain to be fully understood. The
      BCL2-like protein CED-9 of Caenorhabditis elegans has previously been shown to
      promote mitochondrial fusion by physically interacting with the mitochondrial
      fusion protein FZO-1. Here, we report that CED-9 also physically interacts with
      the mitochondrial fission protein DRP-1 and that this interaction can be enhanced
      when CED-9 is associated with the BH3-only protein EGL-1. In addition, we show
      that the EGL-1-CED-9 complex promotes mitochondrial fission by recruiting DRP-1
      to mitochondria and that the egl-1 gene is required for CED-9-dependent
      mitochondrial fission in vivo. Based on these results, we propose that EGL-1
      converts CED-9 into a mitochondrial receptor for DRP-1, thereby shifting its
      activity from profusion to profission. We hypothesize that BCL2-like proteins act
      as mitochondrial receptors for DRP-1-like proteins in higher organisms as well
      and that BH3-only proteins play a general role as modifiers of the function in
      mitochondrial dynamics of BCL2-like proteins. We speculate that this function of
      BCL2-like proteins may be as couplers of mitochondrial fusion and fission.

PMID- 21949253
TI  - In patients hospitalised with acute heart failure, nesiritide, compared with
      placebo, is not associated with improvements in dyspnoea or 30-day
      rehospitalisation or mortality.

PMID- 21949254
TI  - Management of patients hospitalised with community-acquired pneumonia:
      dexamethasone reduces length of stay by 1 day.

PMID- 21949255
TI  - Early (at 34-35 weeks) external cephalic version reduced the risk of non-cephalic
      (breech) presentation at birth but has no effect on risk of caesarean section.

PMID- 21949256
TI  - beta-blockers associated with reduced all-cause mortality in COPD.

PMID- 21949257
TI  - Intensive statin therapy, compared with moderate dose, increases risk of new
      onset diabetes but decreases risk of cardiovascular events.

PMID- 21949258
TI  - Inhaled anticholinergic medications in older men with chronic obstructive
      pulmonary disorder are associated with increased odds of acute urinary retention.

PMID- 21949259
TI  - Ovarian cancer screening has no effect on disease-specific mortality.

PMID- 21949260
TI  - The administration of corticosteroids to 34-36-week pregnant women at risk of
      imminent delivery does not reduce the risk of respiratory disorders in the
      newborn.

PMID- 21949261
TI  - In two parallel pragmatic equivalence trials, leukotriene receptor antagonists as
      initial therapy for asthma compared with inhaled corticosteroids and as add on
      therapy to ICS compared with adding long-acting beta agonists provided equivalent
      short-term asthma quality of life but were associated with more medication
      switches.

PMID- 21949262
TI  - Two sputum samples at once for diagnosis of tuberculosis in Africa has equivalent
      sensitivity and specificity to the standard initial sample followed by a morning
      sample strategy.

PMID- 21949263
TI  - A 2-year early childhood psychosocial stimulation programme improves cognitive
      outcomes and decreases violent behaviour at 22 years for children with growth
      retardation.

PMID- 21949264
TI  - Editorial: Orthology and applications.

PMID- 21949265
TI  - Obituary: Walter Fitch and the orthology paradigm.

PMID- 21949266
TI  - Models, algorithms and programs for phylogeny reconciliation.
AB  - Gene sequences contain a gold mine of phylogenetic information. But unfortunately
      for taxonomists this information does not only tell the story of the species from
      which it was collected. Genes have their own complex histories which record
      speciation events, of course, but also many other events. Among them, gene
      duplications, transfers and losses are especially important to identify. These
      events are crucial to account for when reconstructing the history of species, and
      they play a fundamental role in the evolution of genomes, the diversification of
      organisms and the emergence of new cellular functions. We review reconciliations
      between gene and species trees, which are rigorous approaches for identifying
      duplications, transfers and losses that mark the evolution of a gene family.
      Existing reconciliation models and algorithms are reviewed and difficulties in
      modeling gene transfers are discussed. We also compare different reconciliation
      programs along with their advantages and disadvantages.

PMID- 21949267
TI  - Monovalent and divalent salt correction algorithms for Tm prediction-
      recommendations for Primer3 usage.
AB  - Primer3 is a widely used program for selection of oligonucleotide primers for
      PCR. The websites used for implementation of Primer3 have recently been updated.
      PCR requires Mg(2+)(,) which has a significant dsDNA stabilizing effect that must
      be taken into account when designing PCR primers. The data sets and formulas used
      to correct for salt concentrations have been updated in Primer3 to give better
      prediction of melting temperature (T(m)). The liberal combination of different
      formulas for monovalent and divalent salt correction can lead to different
      results, depending on the formula chosen by the user. Using published T(m) for
      475 different oligonucleotides, it is shown that the combination of the
      implemented conversion of divalent to monovalent cation concentration works well
      with one salt correction formula but not with an alternative one. Use of a more
      recently described alternative formula would lead to equally good T(m)
      predictions if divalent cations are present. The proper selection of compatible
      primer pairs depends on the choice of a good combination of salt correction
      formulas. Currently the SantaLucia salt correction formula should be used if
      Mg(2+) is present. The alternative formula should be updated to its recent form
      for future releases.

PMID- 21949268
TI  - Evolution and applications of plant pathway resources and databases.
AB  - Plants are important sources of food and plant products are essential for modern
      human life. Plants are increasingly gaining importance as drug and fuel
      resources, bioremediation tools and as tools for recombinant technology.
      Considering these applications, database infrastructure for plant model systems
      deserves much more attention. Study of plant biological pathways, the
      interconnection between these pathways and plant systems biology on the whole has
      in general lagged behind human systems biology. In this article we review plant
      pathway databases and the resources that are currently available. We lay out
      trends and challenges in the ongoing efforts to integrate plant pathway databases
      and the applications of database integration. We also discuss how progress in non
      plant communities can serve as an example for the improvement of the plant
      pathway database landscape and thereby allow quantitative modeling of plant
      biosystems. We propose Good Database Practice as a possible model for
      collaboration and to ease future integration efforts.

PMID- 21949269
TI  - Weakly supervised learning of information structure of scientific abstracts--is
      it accurate enough to benefit real-world tasks in biomedicine?
AB  - MOTIVATION: Many practical tasks in biomedicine require accessing specific types
      of information in scientific literature; e.g. information about the methods,
      results or conclusions of the study in question. Several approaches have been
      developed to identify such information in scientific journal articles. The best
      of these have yielded promising results and proved useful for biomedical text
      mining tasks. However, relying on fully supervised machine learning (ml) and a
      large body of annotated data, existing approaches are expensive to develop and
      port to different tasks. A potential solution to this problem is to employ weakly
      supervised learning instead. In this article, we investigate a weakly supervised
      approach to identifying information structure according to a scheme called
      Argumentative Zoning (az). We apply four weakly supervised classifiers to
      biomedical abstracts and evaluate their performance both directly and in a real
      life scenario in the context of cancer risk assessment. RESULTS: Our best weakly
      supervised classifier (based on the combination of active learning and self
      training) performs well on the task, outperforming our best supervised
      classifier: it yields a high accuracy of 81% when just 10% of the labeled data is
      used for training. When cancer risk assessors are presented with the resulting
      annotated abstracts, they find relevant information in them significantly faster
      than when presented with unannotated abstracts. These results suggest that weakly
      supervised learning could be used to improve the practical usefulness of
      information structure for real-life tasks in biomedicine.

PMID- 21949270
TI  - PIDO: the primary immunodeficiency disease ontology.
AB  - MOTIVATION: Primary immunodeficiency diseases (PIDs) are Mendelian conditions of
      high phenotypic complexity and low incidence. They usually manifest in toddlers
      and infants, although they can also occur much later in life. Information about
      PIDs is often widely scattered throughout the clinical as well as the research
      literature and hard to find for both generalists as well as experienced
      clinicians. Semantic Web technologies coupled to clinical information systems can
      go some way toward addressing this problem. Ontologies are a central component of
      such a system, containing and centralizing knowledge about primary
      immunodeficiencies in both a human- and computer-comprehensible form. The
      development of an ontology of PIDs is therefore a central step toward developing
      informatics tools, which can support the clinician in the diagnosis and treatment
      of these diseases. RESULTS: We present PIDO, the primary immunodeficiency disease
      ontology. PIDO characterizes PIDs in terms of the phenotypes commonly observed by
      clinicians during a diagnosis process. Phenotype terms in PIDO are formally
      defined using complex definitions based on qualities, functions, processes and
      structures. We provide mappings to biomedical reference ontologies to ensure
      interoperability with ontologies in other domains. Based on PIDO, we developed
      the PIDFinder, an ontology-driven software prototype that can facilitate clinical
      decision support. PIDO connects immunological knowledge across resources within a
      common framework and thereby enables translational research and the development
      of medical applications for the domain of immunology and primary immunodeficiency
      diseases.

PMID- 21949271
TI  - Pybedtools: a flexible Python library for manipulating genomic datasets and
      annotations.
AB  - SUMMARY: pybedtools is a flexible Python software library for manipulating and
      exploring genomic datasets in many common formats. It provides an intuitive
      Python interface that extends upon the popular BEDTools genome arithmetic tools.
      The library is well documented and efficient, and allows researchers to quickly
      develop simple, yet powerful scripts that enable complex genomic analyses.
      AVAILABILITY: pybedtools is maintained under the GPL license. Stable versions of
      pybedtools as well as documentation are available on the Python Package Index at
      http://pypi.python.org/pypi/pybedtools. CONTACT: dalerr@niddk.nih.gov;
      arq5x@virginia.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at
      Bioinformatics online.

PMID- 21949272
TI  - RASP: rapid modeling of protein side chain conformations.
AB  - MOTIVATION: Modeling of side chain conformations constitutes an indispensable
      effort in protein structure modeling, protein-protein docking and protein design.
      Thanks to an intensive attention to this field, many of the existing programs can
      achieve reasonably good and comparable prediction accuracy. Moreover, in our
      previous work on CIS-RR, we argued that the prediction with few atomic clashes
      can complement the current existing methods for subsequent analysis and
      refinement of protein structures. However, these recent efforts to enhance the
      quality of predicted side chains have been accompanied by a significant increase
      of computational cost. RESULTS: In this study, by mainly focusing on improving
      the speed of side chain conformation prediction, we present a RApid Side-chain
      Predictor, called RASP. To achieve a much faster speed with a comparable accuracy
      to the best existing methods, we not only employ the clash elimination strategy
      of CIS-RR, but also carefully optimize energy terms and integrate different
      search algorithms. In comprehensive benchmark testings, RASP is over one order of
      magnitude faster (~ 40 times over CIS-RR) than the recently developed methods,
      while achieving comparable or even better accuracy.

PMID- 21949274
TI  - What is EBM?

PMID- 21949273
TI  - ISPyB: an information management system for synchrotron macromolecular
      crystallography.
AB  - MOTIVATION: Individual research groups now analyze thousands of samples per year
      at synchrotron macromolecular crystallography (MX) resources. The efficient
      management of experimental data is thus essential if the best possible
      experiments are to be performed and the best possible data used in downstream
      processes in structure determination pipelines. Information System for Protein
      crystallography Beamlines (ISPyB), a Laboratory Information Management System
      (LIMS) with an underlying data model allowing for the integration of analyses
      down-stream of the data collection experiment was developed to facilitate such
      data management. RESULTS: ISPyB is now a multisite, generic LIMS for synchrotron
      based MX experiments. Its initial functionality has been enhanced to include
      improved sample tracking and reporting of experimental protocols, the direct
      ranking of the diffraction characteristics of individual samples and the
      archiving of raw data and results from ancillary experiments and post-experiment
      data processing protocols. This latter feature paves the way for ISPyB to play a
      central role in future macromolecular structure solution pipelines and validates
      the application of the approach used in ISPyB to other experimental techniques,
      such as biological solution Small Angle X-ray Scattering and spectroscopy, which
      have similar sample tracking and data handling requirements.

PMID- 21949275
TI  - Impact of facilitating physician access to relevant medical literature on
      outcomes of hospitalised internal medicine patients: a randomised controlled
      trial.
AB  - INTRODUCTION: There is limited high-quality evidence regarding the usefulness of
      bibliographic assistance in improving clinically important outcomes in
      hospitalised patients. This study was designed to evaluate the impact of
      providing attending physicians with bibliographic information to assist them in
      answering medical questions that arise during daily clinical practice. METHODS:
      All patients admitted to the Internal Medicine ward of Hospital Aleman in Buenos
      Aires between March and August 2010 were randomly assigned to one of two groups:
      intervention or control. Throughout this period, the medical questions that arose
      during morning rounds were identified. Bibliographic research was conducted to
      answer only those questions that emerged during the discussion of patients
      assigned to the intervention group. The compiled information was sent via e-mail
      to all members of the medical team. RESULTS: 809 patients were included in the
      study, 407 were randomly assigned to a search-supported group and 402 to a
      control group. There was no significant difference in death or transfer to an
      intensive care unit (ICU) (RR 1.09 (95% CI 0.7 to 1.6)), rehospitalisation (RR
      1.0 (95% CI 0.7 to 1.3)) or length of hospitalisation (6.5 vs 6.0 days, p=0.25).
      The subgroup of search-supported physicians' patients (n=31), whose attending
      physicians received hand-delivered information, had a significantly lower risk of
      death or transfer to an ICU compared with the control group (0% vs 13.7%,
      p=0.03). CONCLUSIONS: The impact of bibliographic assistance on clinically
      important outcomes could not be proven by this study. However, results suggest
      that some interventions, such as delivering information by hand, might be
      beneficial in a subgroup of inpatients.

PMID- 21949276
TI  - End-of-life care in two Norwegian nursing homes: family perspectives.

PMID- 21949277
TI  - Women who receive continuous support during labour have reduced risk of
      caesarean, instrumental delivery or need for analgesia compared to usual care.
AB  - IMPLICATIONS FOR PRACTICE: Models of care supporting continuous support during
      labour were shown to be more likely to result in a spontaneous vaginal birth.
      Women receiving continuous support required less analgesia and were less likely
      to report negative feelings about the birth experience. Women receiving
      continuous support experienced shorter labours and their babies were less likely
      to have low 5-min Agpar scores. Therefore, such models of care should be
      considered for more extensive implementation in clinical practice settings.

PMID- 21949278
TI  - Motivational interviewing improves patients' mood and reduces mortality 12 months
      poststroke.

PMID- 21949279
TI  - In previously continent adults, aged 70 or older, use of urinary catheters or
      diapers while in hospital increases the risk of new urinary incontinence.

PMID- 21949280
TI  - Experiences of 12 patients in the first 2 years following spinal cord injury:
      setting meaningful rehabilitation goals.

PMID- 21949281
TI  - Pregnant women who experienced late stillbirth appear less likely to have slept
      on their left.

PMID- 21949282
TI  - Installation of safety devices reduces the risk of home injury in children.

PMID- 21949283
TI  - Social aspect of activity stimuli is related to positive affect in persons with
      Alzheimer's disease.

PMID- 21949284
TI  - Multimodality imaging before, during, and after percutaneous mitral valve repair.

PMID- 21949351
TI  - Modeling abnormal early development with induced pluripotent stem cells from
      aneuploid syndromes.
AB  - Many human diseases share a developmental origin that manifests during childhood
      or maturity. Aneuploid syndromes are caused by supernumerary or reduced number of
      chromosomes and represent an extreme example of developmental disease, as they
      have devastating consequences before and after birth. Investigating how
      alterations in gene dosage drive these conditions is relevant because it might
      help treat some clinical aspects. It may also provide explanations as to how
      quantitative differences in gene expression determine phenotypic diversity and
      disease susceptibility among natural populations. Here, we aimed to produce
      induced pluripotent stem cell (iPSC) lines that can be used to improve our
      understanding of aneuploid syndromes. We have generated iPSCs from monosomy X
      [Turner syndrome (TS)], trisomy 8 (Warkany syndrome 2), trisomy 13 (Patau
      syndrome) and partial trisomy 11;22 (Emanuel syndrome), using either skin
      fibroblasts from affected individuals or amniocytes from antenatal diagnostic
      tests. These cell lines stably maintain the karyotype of the donors and behave
      like embryonic stem cells in all tested assays. TS iPSCs were used for further
      studies including global gene expression analysis and tissue-specific directed
      differentiation. Multiple clones displayed lower levels of the pseudoautosomal
      genes ASMTL and PPP2R3B than the controls. Moreover, they could be transformed
      into neural-like, hepatocyte-like and heart-like cells, but displayed
      insufficient up-regulation of the pseudoautosomal placental gene CSF2RA during
      embryoid body formation. These data support that abnormal organogenesis and early
      lethality in TS are not caused by a tissue-specific differentiation blockade, but
      rather involves other abnormalities including impaired placentation.

PMID- 21949352
TI  - Protein interacting with C kinase (PICK1) is a suppressor of spinocerebellar
      ataxia 3-associated neurodegeneration in Drosophila.
AB  - Spinocerebellar ataxia 3 (SCA3) is the most common autosomal dominant ataxia. The
      disease is caused by an expansion of a CAG-trinucelotide repeat region within the
      coding sequence of the ATXN3 gene, and this results in an expanded polyglutamine
      (polyQ) tract within the Ataxin-3 protein. The polyQ expansion leads to neuronal
      dysfunction and cell death. Here, we tested the ability of a number of proteins
      that interact with Ataxin-3 to modulate SCA3 pathogenicity using Drosophila. Of
      10 candidates, we found four novel enhancers and one suppressor. The suppressor,
      PICK1 (Protein interacting with C kinase 1), is a transport protein that
      regulates the trafficking of ion channel subunits involved in calcium homeostasis
      to and from the plasma membrane. In line with calcium homeostasis being a
      potential pathway mis-regulated in SCA3, we also found that down-regulation of
      Nach, an acid sensing ion channel, mitigates SCA3 pathogenesis in flies.
      Modulation of PICK1 could be targeted in other neurodegenerative diseases, as the
      toxicity of SCA1 and tau was also suppressed when PICK1 was down-regulated. These
      findings indicate that interaction proteins may define a rich source of modifier
      pathways to target in disease situations.

PMID- 21949353
TI  - Expression of the dystrophin isoform Dp116 preserves functional muscle mass and
      extends lifespan without preventing dystrophy in severely dystrophic mice.
AB  - Dp116 is a non-muscle isoform of dystrophin that assembles the dystrophin
      glycoprotein complex (DGC), but lacks actin-binding domains. To examine the
      functional role of the DGC, we expressed the Dp116 transgene in mice lacking both
      dystrophin and utrophin (mdx:utrn(-/-)). Unexpectedly, expression of Dp116
      prevented the most severe aspects of the mdx:utrn(-/-) phenotype. Dp116:mdx:utrn(
      /-) transgenic mice had dramatic improvements in growth, mobility and lifespan
      compared with controls. This was associated with increased muscle mass and force
      generating capacity of limb muscles, although myofiber size and specific force
      were unchanged. Conversely, Dp116 had no effect on dystrophic injury as
      determined by muscle histopathology and serum creatine kinase levels. Dp116 also
      failed to restore normal fiber-type distribution or the post-synaptic
      architecture of the neuromuscular junction. These data demonstrate that the DGC
      is critical for growth and maintenance of muscle mass, a function that is
      independent of the ability to prevent dystrophic pathophysiology. Likewise, this
      is the first demonstration in skeletal muscle of a positive functional role for a
      dystrophin protein that lacks actin-binding domains. We conclude that both
      mechanical and non-mechanical functions of dystrophin are important for its role
      in skeletal muscle.

PMID- 21949355
TI  - Results of the Regional Earthquake Likelihood Models (RELM) test of earthquake
      forecasts in California.
AB  - The Regional Earthquake Likelihood Models (RELM) test of earthquake forecasts in
      California was the first competitive evaluation of forecasts of future earthquake
      occurrence. Participants submitted expected probabilities of occurrence of M >=
      4.95 earthquakes in 0.1 degrees  * 0.1 degrees  cells for the period 1 January 1,
      2006, to December 31, 2010. Probabilities were submitted for 7,682 cells in
      California and adjacent regions. During this period, 31 M >= 4.95 earthquakes
      occurred in the test region. These earthquakes occurred in 22 test cells. This
      seismic activity was dominated by earthquakes associated with the M = 7.2, April
      4, 2010, El Mayor-Cucapah earthquake in northern Mexico. This earthquake occurred
      in the test region, and 16 of the other 30 earthquakes in the test region could
      be associated with it. Nine complete forecasts were submitted by six
      participants. In this paper, we present the forecasts in a way that allows the
      reader to evaluate which forecast is the most "successful" in terms of the
      locations of future earthquakes. We conclude that the RELM test was a success and
      suggest ways in which the results can be used to improve future forecasts.

PMID- 21949354
TI  - ALS mutations in FUS cause neuronal dysfunction and death in Caenorhabditis
      elegans by a dominant gain-of-function mechanism.
AB  - It is unclear whether mutations in fused in sarcoma (FUS) cause familial
      amyotrophic lateral sclerosis via a loss-of-function effect due to titrating FUS
      from the nucleus or a gain-of-function effect from cytoplasmic overabundance. To
      investigate this question, we generated a series of independent Caenorhabditis
      elegans lines expressing mutant or wild-type (WT) human FUS. We show that mutant
      FUS, but not WT-FUS, causes cytoplasmic mislocalization associated with
      progressive motor dysfunction and reduced lifespan. The severity of the mutant
      phenotype in C. elegans was directly correlated with the severity of the illness
      caused by the same mutation in humans, arguing that this model closely replicates
      key features of the human illness. Importantly, the mutant phenotype could not be
      rescued by overexpression of WT-FUS, even though WT-FUS had physiological
      intracellular localization, and was not recruited to the cytoplasmic mutant FUS
      aggregates. Our data suggest that FUS mutants cause neuronal dysfunction by a
      dominant gain-of-function effect related either to neurotoxic aggregates of
      mutant FUS in the cytoplasm or to dysfunction in its RNA-binding functions.

PMID- 21949350
TI  - Functional genomic screen and network analysis reveal novel modifiers of
      tauopathy dissociated from tau phosphorylation.
AB  - A functional genetic screen using loss-of-function and gain-of-function alleles
      was performed to identify modifiers of tau-induced neurotoxicity using the 2N/4R
      (full-length) isoform of wild-type human tau expressed in the fly retina. We
      previously reported eye pigment mutations, which create dysfunctional lysosomes,
      as potent modifiers; here, we report 37 additional genes identified from ~1900
      genes screened, including the kinases shaggy/GSK-3beta, par-1/MARK, CamKI and
      Mekk1. Tau acts synergistically with Mekk1 and p38 to down-regulate extracellular
      regulated kinase activity, with a corresponding decrease in AT8 immunoreactivity
      (pS202/T205), suggesting that tau can participate in signaling pathways to
      regulate its own kinases. Modifiers showed poor correlation with tau
      phosphorylation (using the AT8, 12E8 and AT270 epitopes); moreover, tested
      suppressors of wild-type tau were equally effective in suppressing toxicity of a
      phosphorylation-resistant S11A tau construct, demonstrating that changes in tau
      phosphorylation state are not required to suppress or enhance its toxicity. Genes
      related to autophagy, the cell cycle, RNA-associated proteins and chromatin
      binding proteins constitute a large percentage of identified modifiers. Other
      functional categories identified include mitochondrial proteins, lipid
      trafficking, Golgi proteins, kinesins and dynein and the Hsp70/Hsp90-organizing
      protein (Hop). Network analysis uncovered several other genes highly associated
      with the functional modifiers, including genes related to the PI3K, Notch,
      BMP/TGF-beta and Hedgehog pathways, and nuclear trafficking. Activity of GSK
      3beta is strongly upregulated due to TDP-43 expression, and reduced GSK-3beta
      dosage is also a common suppressor of Abeta42 and TDP-43 toxicity. These findings
      suggest therapeutic targets other than mitigation of tau phosphorylation.

PMID- 21949356
TI  - Rumi functions as both a protein O-glucosyltransferase and a protein O
      xylosyltransferase.
AB  - Mutations in rumi result in a temperature-sensitive loss of Notch signaling in
      Drosophila. Drosophila Rumi is a soluble, endoplasmic reticulum-retained protein
      with a CAP10 domain that functions as a protein O-glucosyltransferase. In human
      and mouse genomes, three potential Rumi homologues exist: one with a high degree
      of identity to Drosophila Rumi (52%), and two others with lower degrees of
      identity but including a CAP10 domain (KDELC1 and KDELC2). Here we show that both
      mouse and human Rumi, but not KDELC1 or KDELC2, catalyze transfer of glucose from
      UDP-glucose to an EGF repeat from human factor VII. Similarly, human Rumi, but
      not KDELC1 or KDELC2, rescues the Notch phenotypes in Drosophila rumi clones.
      During characterization of the Rumi enzymes, we noted that, in addition to
      protein O-glucosyltransferase activity, both mammalian and Drosophila Rumi also
      showed significant protein O-xylosyltransferase activity. Rumi transfers Xyl or
      glucose to serine 52 in the O-glucose consensus sequence ( ) of factor VII EGF
      repeat. Surprisingly, the second serine (S53) facilitates transfer of Xyl, but
      not glucose, to the EGF repeat by Rumi. EGF16 of mouse Notch2, which has a
      diserine motif in the consensus sequence ( ), is also modified with either O-Xyl
      or O-glucose glycans in cells. Mutation of the second serine (S590A) causes a
      loss of O-Xyl but not O-glucose at this site. Altogether, our data establish dual
      substrate specificity for the glycosyltransferase Rumi and provide evidence that
      amino acid sequences of the recipient EGF repeat significantly influence which
      donor substrate (UDP-glucose or UDP-Xyl) is used.

PMID- 21949357
TI  - Nuclear receptor liver receptor homologue 1 (LRH-1) regulates pancreatic cancer
      cell growth and proliferation.
AB  - An essential regulator of gene transcription, nuclear receptor liver receptor
      homologue 1 (LRH-1) controls cell differentiation in the developing pancreas and
      maintains cholesterol homeostasis in adults. Recent genome-wide association
      studies linked mutations in the LRH-1 gene and its up-stream regulatory regions
      to development of pancreatic cancer. In this work, we show that LRH-1
      transcription is activated up to 30-fold in human pancreatic cancer cells
      compared to normal pancreatic ductal epithelium. This activation correlates with
      markedly increased LRH-1 protein expression in human pancreatic ductal
      adenocarcinomas in vivo. Selective blocking of LRH-1 by receptor specific siRNA
      significantly inhibits pancreatic cancer cell proliferation in vitro. The
      inhibition is tracked in part to the attenuation of the receptor's
      transcriptional targets controlling cell growth, proliferation, and
      differentiation. Previously, LRH-1 was shown to contribute to formation of
      intestinal tumors. This study demonstrates the critical involvement of LRH-1 in
      development and progression of pancreatic cancer, suggesting the LRH-1 receptor
      as a plausible therapeutic target for treatment of pancreatic ductal
      adenocarcinomas.

PMID- 21949358
TI  - Optimal concentrations in nectar feeding.
AB  - Nectar drinkers must feed quickly and efficiently due to the threat of predation.
      While the sweetest nectar offers the greatest energetic rewards, the sharp
      increase of viscosity with sugar concentration makes it the most difficult to
      transport. We here demonstrate that the sugar concentration that optimizes energy
      transport depends exclusively on the drinking technique employed. We identify
      three nectar drinking techniques: active suction, capillary suction, and viscous
      dipping. For each, we deduce the dependence of the volume intake rate on the
      nectar viscosity and thus infer an optimal sugar concentration consistent with
      laboratory measurements. Our results provide the first rationale for why suction
      feeders typically pollinate flowers with lower sugar concentration nectar than
      their counterparts that use viscous dipping.

PMID- 21949359
TI  - Valuation of plug-in vehicle life-cycle air emissions and oil displacement
      benefits.
AB  - We assess the economic value of life-cycle air emissions and oil consumption from
      conventional vehicles, hybrid-electric vehicles (HEVs), plug-in hybrid-electric
      vehicles (PHEVs), and battery electric vehicles in the US. We find that plug-in
      vehicles may reduce or increase externality costs relative to grid-independent
      HEVs, depending largely on greenhouse gas and SO(2) emissions produced during
      vehicle charging and battery manufacturing. However, even if future marginal
      damages from emissions of battery and electricity production drop dramatically,
      the damage reduction potential of plug-in vehicles remains small compared to
      ownership cost. As such, to offer a socially efficient approach to emissions and
      oil consumption reduction, lifetime cost of plug-in vehicles must be competitive
      with HEVs. Current subsidies intended to encourage sales of plug-in vehicles with
      large capacity battery packs exceed our externality estimates considerably, and
      taxes that optimally correct for externality damages would not close the gap in
      ownership cost. In contrast, HEVs and PHEVs with small battery packs reduce
      externality damages at low (or no) additional cost over their lifetime. Although
      large battery packs allow vehicles to travel longer distances using electricity
      instead of gasoline, large packs are more expensive, heavier, and more emissions
      intensive to produce, with lower utilization factors, greater charging
      infrastructure requirements, and life-cycle implications that are more sensitive
      to uncertain, time-sensitive, and location-specific factors. To reduce air
      emission and oil dependency impacts from passenger vehicles, strategies to
      promote adoption of HEVs and PHEVs with small battery packs offer more social
      benefits per dollar spent.

PMID- 21949360
TI  - Direct measurement of the protein response to an electrostatic perturbation that
      mimics the catalytic cycle in ketosteroid isomerase.
AB  - Understanding how electric fields and their fluctuations in the active site of
      enzymes affect efficient catalysis represents a critical objective of biochemical
      research. We have directly measured the dynamics of the electric field in the
      active site of a highly proficient enzyme, Delta(5)-3-ketosteroid isomerase
      (KSI), in response to a sudden electrostatic perturbation that simulates the
      charge displacement that occurs along the KSI catalytic reaction coordinate.
      Photoexcitation of a fluorescent analog (coumarin 183) of the reaction
      intermediate mimics the change in charge distribution that occurs between the
      reactant and intermediate state in the steroid substrate of KSI. We measured the
      electrostatic response and angular dynamics of four probe dipoles in the enzyme
      active site by monitoring the time-resolved changes in the vibrational absorbance
      (IR) spectrum of a spectator thiocyanate moiety (a quantitative sensor of changes
      in electric field) placed at four different locations in and around the active
      site, using polarization-dependent transient vibrational Stark spectroscopy. The
      four different dipoles in the active site remain immobile and do not align to the
      changes in the substrate electric field. These results indicate that the active
      site of KSI is preorganized with respect to functionally relevant changes in
      electric fields.

PMID- 21949361
TI  - Speed limit of protein folding evidenced in secondary structure dynamics.
AB  - As the simplest and most prevalent motif of protein folding, alpha-helix
      initiation is the starting point of macromolecular complexity. In this work,
      helix initiation was directly measured via ultrafast temperature-jump
      spectroscopy on the smallest possible helix nucleus for which only the first turn
      is formed. The rate's dependence on sequence, length, and temperature reveals the
      fastest possible events in protein folding dynamics, and it was possible to
      separate the rate-limiting torsional (conformational) diffusion from the fast
      annealing of the helix. An analytic coarse-grained model for this process, which
      predicts the initiation rate as a function of temperature, confirms this picture.
      Moreover, the stipulations of the model were verified by ensemble-converging all
      atom molecular dynamics simulations, which reproduced both the picosecond
      annealing and the nanosecond diffusion processes observed experimentally.

PMID- 21949362
TI  - Replacement of histone H3 with CENP-A directs global nucleosome array
      condensation and loosening of nucleosome superhelical termini.
AB  - Centromere protein A (CENP-A) is a histone H3 variant that marks centromere
      location on the chromosome. To study the subunit structure and folding of human
      CENP-A-containing chromatin, we generated a set of nucleosomal arrays with
      canonical core histones and another set with CENP-A substituted for H3. At the
      level of quaternary structure and assembly, we find that CENP-A arrays are
      composed of octameric nucleosomes that assemble in a stepwise mechanism,
      recapitulating conventional array assembly with canonical histones. At
      intermediate structural resolution, we find that CENP-A-containing arrays are
      globally condensed relative to arrays with the canonical histones. At high
      structural resolution, using hydrogen-deuterium exchange coupled to mass
      spectrometry (H/DX-MS), we find that the DNA superhelical termini within each
      nucleosome are loosely connected to CENP-A, and we identify the key amino acid
      substitution that is largely responsible for this behavior. Also the C terminus
      of histone H2A undergoes rapid hydrogen exchange relative to canonical arrays and
      does so in a manner that is independent of nucleosomal array folding. These
      findings have implications for understanding CENP-A-containing nucleosome
      structure and higher-order chromatin folding at the centromere.

PMID- 21949363
TI  - Ultrasensitive detection of protein translocated through toxin pores in droplet
      interface bilayers.
AB  - Many bacterial toxins form proteinaceous pores that facilitate the translocation
      of soluble effector proteins across cellular membranes. With anthrax toxin this
      process may be monitored in real time by electrophysiology, where fluctuations in
      ionic current through these pores inserted in model membranes are used to infer
      the translocation of individual protein molecules. However, detecting the minute
      quantities of translocated proteins has been a challenge. Here, we describe use
      of the droplet-interface bilayer system to follow the movement of proteins across
      a model membrane separating two submicroliter aqueous droplets. We report the
      capture and subsequent direct detection of as few as 100 protein molecules that
      have translocated through anthrax toxin pores. The droplet-interface bilayer
      system offers new avenues of approach to the study of protein translocation.

PMID- 21949364
TI  - InfoBiology by printed arrays of microorganism colonies for timed and on-demand
      release of messages.
AB  - This paper presents a proof-of-principle method, called InfoBiology, to write and
      encode data using arrays of genetically engineered strains of Escherichia coli
      with fluorescent proteins (FPs) as phenotypic markers. In InfoBiology, we encode,
      send, and release information using living organisms as carriers of data.
      Genetically engineered systems offer exquisite control of both genotype and
      phenotype. Living systems also offer the possibility for timed release of
      information as phenotypic features can take hours or days to develop. We use
      growth media and chemically induced gene expression as cipher keys or
      "biociphers" to develop encoded messages. The messages, called Steganography by
      Printed Arrays of Microbes (SPAM), consist of a matrix of spots generated by
      seven strains of E. coli, with each strain expressing a different FP. The coding
      scheme for these arrays relies on strings of paired, septenary digits, where each
      pair represents an alphanumeric character. In addition, the photophysical
      properties of the FPs offer another method for ciphering messages. Unique
      combinations of excited and emitted wavelengths generate distinct fluorescent
      patterns from the Steganography by Printed Arrays of Microbes (SPAM). This paper
      shows a new form of steganography based on information from engineered living
      systems. The combination of bio- and "photociphers" along with controlled timed
      release exemplify the capabilities of InfoBiology, which could enable biometrics,
      communication through compromised channels, easy-to-read barcoding of biological
      products, or provide a deterrent to counterfeiting.

PMID- 21949365
TI  - Basic peptide-morpholino oligomer conjugate that is very effective in killing
      bacteria by gene-specific and nonspecific modes.
AB  - Basic peptides covalently linked to nucleic acids, or chemically modified nucleic
      acids, enable the insertion of such a conjugate into bacteria grown in liquid
      medium and mammalian cells in tissue culture. A unique peptide, derived from
      human T cells, has been employed in a chemical synthesis to make a conjugate with
      a morpholino oligonucleotide. This new conjugate is at least 10- to 100-fold more
      effective than previous peptides used in altering the phenotype of host bacteria
      if the external guide sequence methodology is employed in these experiments.
      Bacteria with target genes expressing chloramphenicol resistance, penicillin
      resistance, or gyrase A function can effectively be reduced in their expression
      and the host cells killed. Several bacteria are susceptible to this treatment,
      which has a broad range of potency. The loss in viability of bacteria is not due
      only to complementarity with a target RNA and the action of RNase P, but also to
      a non-gene-specific tight binding of the complexed nontargeted RNA to the basic
      polypeptide-morpholino oligonucleotide.

PMID- 21949366
TI  - mTOR links incretin signaling to HIF induction in pancreatic beta cells.
AB  - Under feeding conditions, the incretin hormone GLP-1 promotes pancreatic islet
      viability by triggering the cAMP pathway in beta cells. Increases in PKA activity
      stimulate the phosphorylation of CREB, which in turn enhances beta cell survival
      by upregulating IRS2 expression. Although sustained GLP-1 action appears
      important for its salutary effects on islet function, the transient nature of
      CREB activation has pointed to the involvement of additional nuclear factors in
      this process. Following the acute induction of CREB-regulated genes, cAMP
      triggers a second delayed phase of gene expression that proceeds via the HIF
      transcription factor. Increases in cAMP promote the accumulation of HIF1alpha in
      beta cells by activating the mTOR pathway. As exposure to rapamycin disrupts GLP
      1 effects on beta cell viability, these results demonstrate how a pathway
      associated with tumor growth also mediates salutary effects of an incretin
      hormone on pancreatic islet function.

PMID- 21949367
TI  - UBLCP1 is a 26S proteasome phosphatase that regulates nuclear proteasome
      activity.
AB  - Protein degradation by the 26S proteasome is a fundamental process involved in a
      broad range of cellular activities, yet how proteasome activity is regulated
      remains poorly understood. We report here that ubiquitin-like domain-containing C
      terminal domain phosphatase 1 (UBLCP1) is a 26S proteasome phosphatase that
      regulates nuclear proteasome activity. UBLCP1 directly interacts with the
      proteasome via its UBL domain and is exclusively localized in the nucleus. UBLCP1
      dephosphorylates the 26S proteasome and inhibits proteasome activity in vitro.
      Knockdown of UBLCP1 in cells promotes 26S proteasome assembly and selectively
      enhances nuclear proteasome activity. Our results describe the first identified
      proteasome-specific phosphatase and uncover a unique mechanism for
      phosphoregulation of the proteasome.

PMID- 21949368
TI  - An algorithm-based topographical biomaterials library to instruct cell fate.
AB  - It is increasingly recognized that material surface topography is able to evoke
      specific cellular responses, endowing materials with instructive properties that
      were formerly reserved for growth factors. This opens the window to improve upon,
      in a cost-effective manner, biological performance of any surface used in the
      human body. Unfortunately, the interplay between surface topographies and cell
      behavior is complex and still incompletely understood. Rational approaches to
      search for bioactive surfaces will therefore omit previously unperceived
      interactions. Hence, in the present study, we use mathematical algorithms to
      design nonbiased, random surface features and produce chips of poly(lactic acid)
      with 2,176 different topographies. With human mesenchymal stromal cells (hMSCs)
      grown on the chips and using high-content imaging, we reveal unique, formerly
      unknown, surface topographies that are able to induce MSC proliferation or
      osteogenic differentiation. Moreover, we correlate parameters of the mathematical
      algorithms to cellular responses, which yield novel design criteria for these
      particular parameters. In conclusion, we demonstrate that randomized libraries of
      surface topographies can be broadly applied to unravel the interplay between
      cells and surface topography and to find improved material surfaces.

PMID- 21949369
TI  - Tree preserving embedding.
AB  - The goal of dimensionality reduction is to embed high-dimensional data in a low
      dimensional space while preserving structure in the data relevant to exploratory
      data analysis such as clusters. However, existing dimensionality reduction
      methods often either fail to separate clusters due to the crowding problem or can
      only separate clusters at a single resolution. We develop a new approach to
      dimensionality reduction: tree preserving embedding. Our approach uses the
      topological notion of connectedness to separate clusters at all resolutions. We
      provide a formal guarantee of cluster separation for our approach that holds for
      finite samples. Our approach requires no parameters and can handle general types
      of data, making it easy to use in practice and suggesting new strategies for
      robust data visualization.

PMID- 21949370
TI  - Random phase detection in multidimensional NMR.
AB  - Despite advances in resolution accompanying the development of high-field
      superconducting magnets, biomolecular applications of NMR require multiple
      dimensions in order to resolve individual resonances, and the achievable
      resolution is typically limited by practical constraints on measuring time. In
      addition to the need for measuring long evolution times to obtain high
      resolution, the need to distinguish the sign of the frequency constrains the
      ability to shorten measuring times. Sign discrimination is typically accomplished
      by sampling the signal with two different receiver phases or by selecting a
      reference frequency outside the range of frequencies spanned by the signal and
      then sampling at a higher rate. In the parametrically sampled (indirect) time
      dimensions of multidimensional NMR experiments, either method imposes an
      additional factor of 2 sampling burden for each dimension. We demonstrate that by
      using a single detector phase at each time sample point, but randomly altering
      the phase for different points, the sign ambiguity that attends fixed single
      phase detection is resolved. Random phase detection enables a reduction in
      experiment time by a factor of 2 for each indirect dimension, amounting to a
      factor of 8 for a four-dimensional experiment, albeit at the cost of introducing
      sampling artifacts. Alternatively, for fixed measuring time, random phase
      detection can be used to double resolution in each indirect dimension. Random
      phase detection is complementary to nonuniform sampling methods, and their
      combination offers the potential for additional benefits. In addition to
      applications in biomolecular NMR, random phase detection could be useful in
      magnetic resonance imaging and other signal processing contexts.

PMID- 21949371
TI  - A whole-genome RNAi screen identifies an 8q22 gene cluster that inhibits death
      receptor-mediated apoptosis.
AB  - Deregulation of apoptosis is a common occurrence in cancer, for which emerging
      oncology therapeutic agents designed to engage this pathway are undergoing
      clinical trials. With the aim of uncovering strategies to activate apoptosis in
      cancer cells, we used a pooled shRNA screen to interrogate death receptor
      signaling. This screening approach identified 16 genes that modulate the
      sensitivity to ligand induced apoptosis, with several genes exhibiting frequent
      overexpression and/or copy number gain in cancer. Interestingly, two of the top
      hits, EDD1 and GRHL2, are found 50 kb apart on chromosome 8q22, a region that is
      frequently amplified in many cancers. By using a series of silencing and
      overexpression studies, we show that EDD1 and GRHL2 suppress death-receptor
      expression, and that EDD1 expression is elevated in breast, pancreas, and lung
      cancer cell lines resistant to death receptor-mediated apoptosis. Supporting the
      relevance of EDD1 and GRHL2 as therapeutic candidates to engage apoptosis in
      cancer cells, silencing the expression of either gene sensitizes 8q22-amplified
      breast cancer cell lines to death receptor induced apoptosis. Our findings
      highlight a mechanism by which cancer cells may evade apoptosis, and therefore
      provide insight in the search for new targets and functional biomarkers for this
      pathway.

PMID- 21949372
TI  - Inhibition recruitment in prefrontal cortex during sleep spindles and gating of
      hippocampal inputs.
AB  - During light slow-wave sleep, the thalamo-cortical network oscillates in waxing
      and-waning patterns at about 7 to 14 Hz and lasting for 500 ms to 3 s, called
      spindles, with the thalamus rhythmically sending strong excitatory volleys to the
      cortex. Concurrently, the hippocampal activity is characterized by transient and
      strong excitatory events, Sharp-Waves-Ripples (SPWRs), directly affecting
      neocortical activity--in particular the medial prefrontal cortex (mPFC)--which
      receives monosynaptic fibers from the ventral hippocampus and subiculum. Both
      spindles and SPWRs have been shown to be strongly involved in memory
      consolidation. However, the dynamics of the cortical network during natural sleep
      spindles and how prefrontal circuits simultaneously process hippocampal and
      thalamo-cortical activity remain largely undetermined. Using multisite neuronal
      recordings in rat mPFC, we show that during sleep spindles, oscillatory responses
      of cortical cells are different for different cell types and cortical layers.
      Superficial neurons are more phase-locked and tonically recruited during spindle
      episodes. Moreover, in a given layer, interneurons were always more modulated
      than pyramidal cells, both in firing rate and phase, suggesting that the dynamics
      are dominated by inhibition. In the deep layers, where most of the hippocampal
      fibers make contacts, pyramidal cells respond phasically to SPWRs, but not during
      spindles. Similar observations were obtained when analyzing gamma-oscillation
      modulation in the mPFC. These results demonstrate that during sleep spindles, the
      cortex is functionnaly "deafferented" from its hippocampal inputs, based on
      processes of cortical origin, and presumably mediated by the strong recruitment
      of inhibitory interneurons. The interplay between hippocampal and thalamic inputs
      may underlie a global mechanism involved in the consolidation of recently formed
      memory traces.

PMID- 21949373
TI  - Specificity and detection of insulin-reactive CD4+ T cells in type 1 diabetes in
      the nonobese diabetic (NOD) mouse.
AB  - In the nonobese diabetic (NOD) mouse model of type 1 diabetes (T1D), an insulin
      peptide (B:9-23) is a major target for pathogenic CD4(+) T cells. However, there
      is no consensus on the relative importance of the various positions or
      "registers" this peptide can take when bound in the groove of the NOD MHCII
      molecule, IA(g7). This has hindered structural studies and the tracking of the
      relevant T cells in vivo with fluorescent peptide-MHCII tetramers. Using mutated
      B:9-23 peptides and methods for trapping the peptide in particular registers, we
      show that most, if not all, NOD CD4(+) T cells react to B:9-23 bound in low
      affinity register 3. However, these T cells can be divided into two types
      depending on whether their response is improved or inhibited by substituting a
      glycine for the B:21 glutamic acid at the p8 position of the peptide. On the
      basis of these findings, we constructed a set of fluorescent insulin-IA(g7)
      tetramers that bind to most insulin-specific T-cell clones tested. A mixture of
      these tetramers detected a high frequency of B:9-23-reactive CD4(+) T cells in
      the pancreases of prediabetic NOD mice. Our data are consistent with the idea
      that, within the pancreas, unique processing of insulin generates truncated
      peptides that lack or contain the B:21 glutamic acid. In the thymus, the absence
      of this type of processing combined with the low affinity of B:9-23 binding to
      IA(g7) in register 3 may explain the escape of insulin-specific CD4(+) T cells
      from the mechanisms that usually eliminate self-reactive T cells.

PMID- 21949374
TI  - Hypoxia-induced transcriptional repression of the melanoma-associated oncogene
      MITF.
AB  - Microphthalmia-associated transcription factor (MITF) regulates normal melanocyte
      development and is also a lineage-selective oncogene implicated in melanoma and
      clear-cell sarcoma (i.e., melanoma of soft parts). We have observed that MITF
      expression is potently reduced under hypoxic conditions in primary melanocytes
      and melanoma and clear cell sarcoma cells through hypoxia inducible factor 1
      (HIF1)-mediated induction of the transcriptional repressor differentially
      expressed in chondrocytes protein 1 (DEC1) (BHLHE40), which subsequently binds
      and suppresses the promoter of M-MITF (melanocyte-restricted MITF isoform).
      Correspondingly, hypoxic conditions or HIF1alpha stabilization achieved by using
      small-molecule prolyl-hydroxylase inhibitors reduced M-MITF expression, leading
      to melanoma cell growth arrest that was rescued by ectopic expression of M-MITF
      in vitro. Prolyl hydroxylase inhibition also potently suppressed melanoma growth
      in a mouse xenograft model. These studies illuminate a physiologic hypoxia
      response in pigment cells leading to M-MITF suppression, one that suggests a
      potential survival advantage mechanism for MITF amplification in metastatic
      melanoma and offers a small-molecule strategy for suppression of the MITF
      oncogene in vivo.

PMID- 21949376
TI  - Protein delivery using engineered virus-like particles.
AB  - Over the years, researchers have developed several methods to deliver
      macromolecules into the cytosol and nucleus of living cells. However, there are
      limitations to all of these methods. The problems include (i) inefficient uptake,
      (ii) endosomal entrapment, (iii) delivery that is restricted to certain cell
      types, and (iv) damage to cells in the delivery process. Retroviral vectors are
      often used for gene delivery; however, integration of the genome of retroviral
      vector into the host genome can have serious consequences. Here we describe a
      safe alternative in which virus-like particles (VLPs), derived from an avian
      retrovirus, are used to deliver protein to cells. We show that these VLPs are a
      highly adaptable platform that can be used to deliver proteins either as part of
      Gag fusion proteins (intracellular delivery) or on the surface of VLPs. We
      generated VLPs that contain Gag-Cre recombinase, Gag-Fcy::Fur, and Gag-human
      caspase-8 as a proof-of-concept and demonstrated that the encapsidated proteins
      are active in recipient cells. In addition, we show that murine IFN-gamma and
      human TNF-related apoptosis-inducing ligand can be displayed on the surface of
      VLPs, and that these modified VLPs can cause the appropriate response in cells,
      as evidenced by phosphorylation of STAT1 and induction of cell death,
      respectively.

PMID- 21949375
TI  - Grafted human-induced pluripotent stem-cell-derived neurospheres promote motor
      functional recovery after spinal cord injury in mice.
AB  - Once their safety is confirmed, human-induced pluripotent stem cells (hiPSCs),
      which do not entail ethical concerns, may become a preferred cell source for
      regenerative medicine. Here, we investigated the therapeutic potential of
      transplanting hiPSC-derived neurospheres (hiPSC-NSs) into nonobese diabetic (NOD)
      severe combined immunodeficient (SCID) mice to treat spinal cord injury (SCI).
      For this, we used a hiPSC clone (201B7), established by transducing four
      reprogramming factors (Oct3/4, Sox2, Klf4, and c-Myc) into adult human
      fibroblasts. Grafted hiPSC-NSs survived, migrated, and differentiated into the
      three major neural lineages (neurons, astrocytes, and oligodendrocytes) within
      the injured spinal cord. They showed both cell-autonomous and noncell-autonomous
      (trophic) effects, including synapse formation between hiPSC-NS-derived neurons
      and host mouse neurons, expression of neurotrophic factors, angiogenesis, axonal
      regrowth, and increased amounts of myelin in the injured area. These positive
      effects resulted in significantly better functional recovery compared with
      vehicle-treated control animals, and the recovery persisted through the end of
      the observation period, 112 d post-SCI. No tumor formation was observed in the
      hiPSC-NS-grafted mice. These findings suggest that hiPSCs give rise to neural
      stem/progenitor cells that support improved function post-SCI and are a promising
      cell source for its treatment.

PMID- 21949377
TI  - Inhibitory interneurons in a cortical column form hot zones of inhibition in
      layers 2 and 5A.
AB  - Although physiological data on microcircuits involving a few inhibitory neurons
      in the mammalian cerebral cortex are available, data on the quantitative relation
      between inhibition and excitation in cortical circuits involving thousands of
      neurons are largely missing. Because the distribution of neurons is very
      inhomogeneous in the cerebral cortex, it is critical to map all neurons in a
      given volume rather than to rely on sparse sampling methods. Here, we report the
      comprehensive mapping of interneurons (INs) in cortical columns of rat
      somatosensory cortex, immunolabeled for neuron-specific nuclear protein and
      glutamate decarboxylase. We found that a column contains ~2,200 INs (11.5% of
      ~19,000 neurons), almost a factor of 2 less than previously estimated. The
      density of GABAergic neurons was inhomogeneous between layers, with peaks in the
      upper third of L2/3 and in L5A. IN density therefore defines a distinct layer 2
      in the sensory neocortex. In addition, immunohistochemical markers of IN subtypes
      were layer-specific. The "hot zones" of inhibition in L2 and L5A match the
      reported low stimulus-evoked spiking rates of excitatory neurons in these layers,
      suggesting that these inhibitory hot zones substantially suppress activity in the
      neocortex.

PMID- 21949378
TI  - Whole-genome nucleotide diversity, recombination, and linkage disequilibrium in
      the model legume Medicago truncatula.
AB  - Medicago truncatula is a model for investigating legume genetics, including the
      genetics and evolution of legume-rhizobia symbiosis. We used whole-genome
      sequence data to identify and characterize sequence polymorphisms and linkage
      disequilibrium (LD) in a diverse collection of 26 M. truncatula accessions. Our
      analyses reveal that M. truncatula harbors both higher diversity and less LD than
      soybean (Glycine max) and exhibits patterns of LD and recombination similar to
      Arabidopsis thaliana. The population-scaled recombination rate is approximately
      one-third of the mutation rate, consistent with expectations for a species with a
      high selfing rate. Linkage disequilibrium, however, is not extensive, and
      therefore, the low recombination rate is likely not a major constraint to
      adaptation. Nucleotide diversity in 100-kb windows was negatively correlated with
      gene density, which is expected if diversity is shaped by selection acting
      against slightly deleterious mutations. Among putative coding regions, members of
      four gene families harbor significantly higher diversity than the genome-wide
      average. Three of these families are involved in resistance against pathogens;
      one of these families, the nodule-specific, cysteine-rich gene family, is
      specific to the galegoid legumes and is involved in control of rhizobial
      differentiation. The more than 3 million SNPs that we detected, approximately one
      half of which are present in more than one accession, are a valuable resource for
      genome-wide association mapping of genes responsible for phenotypic diversity in
      legumes, especially traits associated with symbiosis and nodulation.

PMID- 21949380
TI  - Human sweet taste receptor mediates acid-induced sweetness of miraculin.
AB  - Miraculin (MCL) is a homodimeric protein isolated from the red berries of
      Richadella dulcifica. MCL, although flat in taste at neutral pH, has taste
      modifying activity to convert sour stimuli to sweetness. Once MCL is held on the
      tongue, strong sweetness is sensed over 1 h each time we taste a sour solution.
      Nevertheless, no molecular mechanism underlying the taste-modifying activity has
      been clarified. In this study, we succeeded in quantitatively evaluating the acid
      induced sweetness of MCL using a cell-based assay system and found that MCL
      activated hT1R2-hT1R3 pH-dependently as the pH decreased from 6.5 to 4.8, and
      that the receptor activation occurred every time an acid solution was applied.
      Although MCL per se is sensory-inactive at pH 6.7 or higher, it suppressed the
      response of hT1R2-hT1R3 to other sweeteners at neutral pH and enhanced the
      response at weakly acidic pH. Using human/mouse chimeric receptors and molecular
      modeling, we revealed that the amino-terminal domain of hT1R2 is required for the
      response to MCL. Our data suggest that MCL binds hT1R2-hT1R3 as an antagonist at
      neutral pH and functionally changes into an agonist at acidic pH, and we conclude
      this may cause its taste-modifying activity.

PMID- 21949379
TI  - Isovaleryl-homoserine lactone, an unusual branched-chain quorum-sensing signal
      from the soybean symbiont Bradyrhizobium japonicum.
AB  - Many species of Proteobacteria communicate by using LuxI-LuxR-type quorum-sensing
      systems that produce and detect acyl-homoserine lactone (acyl-HSL) signals. Most
      of the known signals are straight-chain fatty acyl-HSLs, and evidence indicates
      that LuxI homologs prefer fatty acid-acyl carrier protein (ACP) over fatty acyl
      CoA as the acyl substrate for signal synthesis. Two related LuxI homologs, RpaI
      and BtaI from Rhodopseudomonas palustris and photosynthetic stem-nodulating
      bradyrhizobia, direct production of the aryl-HSLs p-coumaroyl-HSL and cinnamoyl
      HSL, respectively. Here we report that BjaI from the soybean symbiont
      Bradyrhizobium japonicum USDA110 is closely related to RpaI and BtaI and
      catalyzes the synthesis of isovaleryl-HSL (IV-HSL), a branched-chain fatty acyl
      HSL. We show that IV-HSL induces expression of bjaI, and in this way IV-HSL
      functions like many other acyl-HSL quorum-sensing signals. Purified histidine
      tagged BjaI was an IV-HSL synthase, which was active with isovaleryl-CoA but not
      detectably so with isovaleryl-ACP. This suggests that the RpaI-BtaI-BjaI
      subfamily of acyl-HSL synthases may use CoA- rather than ACP-linked substrates
      for acyl-HSL synthesis. The bjaI-linked bjaR(1) gene is involved in the response
      to IV-HSL, and BjaR(1) is sensitive to IV-HSL at concentrations as low as 10 pM.
      Low but sufficient levels of IV-HSL (about 5 nM) accumulate in B. japonicum
      culture fluid. The low levels of IV-HSL synthesis have likely contributed to the
      fact that the quorum-sensing signal from this bacterium has not been described
      elsewhere.

PMID- 21949381
TI  - Critical thresholds and tangible targets for ecosystem-based management of coral
      reef fisheries.
AB  - Sustainably managing ecosystems is challenging, especially for complex systems
      such as coral reefs. This study develops critical reference points for
      sustainable management by using a large empirical dataset on the coral reefs of
      the western Indian Ocean to investigate associations between levels of target
      fish biomass (as an indicator of fishing intensity) and eight metrics of
      ecosystem state. These eight ecological metrics each exhibited specific
      thresholds along a continuum of fishable biomass ranging from heavily fished
      sites to old fisheries closures. Three thresholds lay above and five below a
      hypothesized window of fishable biomass expected to produce a maximum
      multispecies sustainable yield (B(MMSY)). Evaluating three management systems in
      nine countries, we found that unregulated fisheries often operate below the
      B(MMSY), whereas fisheries closures and, less frequently, gear-restricted
      fisheries were within or above this window. These findings provide tangible
      management targets for multispecies coral reef fisheries and highlight key
      tradeoffs required to achieve different fisheries and conservation goals.

PMID- 21949382
TI  - Genomic and physiological footprint of the Deepwater Horizon oil spill on
      resident marsh fishes.
AB  - The biological consequences of the Deepwater Horizon oil spill are unknown,
      especially for resident organisms. Here, we report results from a field study
      tracking the effects of contaminating oil across space and time in resident
      killifish during the first 4 mo of the spill event. Remote sensing and analytical
      chemistry identified exposures, which were linked to effects in fish
      characterized by genome expression and associated gill immunohistochemistry,
      despite very low concentrations of hydrocarbons remaining in water and tissues.
      Divergence in genome expression coincides with contaminating oil and is
      consistent with genome responses that are predictive of exposure to hydrocarbon
      like chemicals and indicative of physiological and reproductive impairment. Oil
      contaminated waters are also associated with aberrant protein expression in gill
      tissues of larval and adult fish. These data suggest that heavily weathered crude
      oil from the spill imparts significant biological impacts in sensitive Louisiana
      marshes, some of which remain for over 2 mo following initial exposures.

PMID- 21949383
TI  - CD4+ T-cell synapses involve multiple distinct stages.
AB  - One very striking feature of T-cell recognition is the formation of an
      immunological synapse between a T cell and a cell that it is recognizing.
      Formation of this complex structure correlates with cytotoxicity in the case of
      killer (largely CD8(+)) T-cell activity, or robust cytokine release and
      proliferation in the case of the much longer lived synapses formed by helper
      (CD4(+)) T cells. Here we have used electron microscopy and 3D tomography to
      characterize the synapses of antigen-specific CD4(+) T cells recognizing B cells
      and dendritic cells at different time points. We show that there are at least
      four distinct stages in synapse formation, proceeding over several hours,
      including an initial stage involving invasive T-cell pseudopodia that penetrate
      deeply into the antigen-presenting cell, almost to the nuclear envelope. This
      must involve considerable force and may serve to widen the search for potential
      ligands on the surface of the cell being recognized. We also show that centrioles
      and the Golgi complex are always located immediately beneath the synapse and that
      centrioles are significantly shifted toward the late contact zone with either B
      lymphocytes or bone marrow-derived dendritic cells such as antigen-presenting
      cells, and that there are dynamic, stage-dependent changes in the organization of
      microtubules beneath the synapse. These data reinforce and extend previous data
      on cytotoxic T cells that one of the principal functions of the immunological
      synapse is to facilitate cytokine secretion into the synaptic cleft, as well as
      provide important insights into the overall dynamics of this phenomenon.

PMID- 21949384
TI  - Complex genetic architecture of Drosophila aggressive behavior.
AB  - Epistasis and pleiotropy feature prominently in the genetic architecture of
      quantitative traits but are difficult to assess in outbred populations. We
      performed a diallel cross among coisogenic Drosophila P-element mutations
      associated with hyperaggressive behavior and showed extensive epistatic and
      pleiotropic effects on aggression, brain morphology, and genome-wide transcript
      abundance in head tissues. Epistatic interactions were often of greater magnitude
      than homozygous effects, and the topology of epistatic networks varied among
      these phenotypes. The transcriptional signatures of homozygous and double
      heterozygous genotypes derived from the six mutations imply a large mutational
      target for aggressive behavior and point to evolutionarily conserved genetic
      mechanisms and neural signaling pathways affecting this universal fitness trait.

PMID- 21949385
TI  - MHC genotypes associate with resistance to a frog-killing fungus.
AB  - The emerging amphibian disease chytridiomycosis is caused by the fungal pathogen
      Batrachochytrium dendrobatidis (Bd). Amphibian populations and species differ in
      susceptibility to Bd, yet we know surprisingly little about the genetic basis of
      this natural variation. MHC loci encode peptides that initiate acquired immunity
      in vertebrates, making them likely candidates for determining disease
      susceptibility. However, MHC genes have never been characterized in the context
      of chytridiomycosis. Here, we performed experimental Bd infections in laboratory
      reared frogs collected from five populations that show natural variation in Bd
      susceptibility. We found that alleles of an expressed MHC class IIB locus
      associate with survival following Bd infection. Across populations, MHC
      heterozygosity was a significant predictor of survival. Within populations, MHC
      heterozygotes and individuals bearing MHC allele Q had a significantly reduced
      risk of death, and we detected a significant signal of positive selection along
      the evolutionary lineage leading to allele Q. Our findings demonstrate that
      immunogenetic variation affects chytridiomycosis survival under controlled
      experimental conditions, confirming that host genetic polymorphisms contribute to
      chytridiomycosis resistance.

PMID- 21949386
TI  - Examining the dynamics of chromosomal passenger complex (CPC)-dependent
      phosphorylation during cell division.
AB  - The dynamic cellular reorganization needed for successful mitosis requires
      regulatory cues that vary across microns. The chromosomal passenger complex (CPC)
      is a conserved regulator involved in key mitotic events such as chromosome
      microtubule attachment and spindle midzone formation. Recently, spatial
      phosphorylation gradients have been reported for CPC substrates, raising the
      possibility that CPC-dependent signaling establishes order on the micron-length
      scale in dividing cells. However, this hypothesis has not been tested, largely
      because of incomplete characterization of the CPC-dependent phosphorylation
      dynamics. Without these data it is difficult to evaluate perturbations of CPC
      signaling and select one that alters the spatial organization of substrate
      phosphorylation at a particular stage of mitosis, without changing overall
      phosphorylation levels. Here we examine the spatiotemporal dynamics of CPC
      dependent phosphorylation along microtubules throughout mitosis using a Forster
      resonance energy transfer-based sensor. We find that a CPC substrate
      phosphorylation gradient, with highest phosphorylation levels between the two
      spindle poles, emerges when a cell enters mitosis. Interestingly, this gradient
      becomes undetectable at metaphase, but can be revealed by partially suppressing
      CPC activity, suggesting that high substrate phosphorylation levels can mask
      persistent CPC-dependent spatial patterning. After anaphase onset, the gradient
      emerges and persists until cell cleavage. Selective mislocalization of the CPC
      during anaphase suppresses gradient formation, but overall substrate
      phosphorylation levels remain unchanged. Under these conditions, the spindle
      midzone fails to organize and function properly. Our findings suggest a model in
      which the CPC establishes phosphorylation gradients to coordinate the
      spatiotemporal dynamics needed for error-free cell division.

PMID- 21949387
TI  - Essential role of Mediator subunit Med1 in invariant natural killer T-cell
      development.
AB  - CD1d-restricted invariant NKT (iNKT) cells are a unique lineage of T lymphocytes
      that regulate both innate and adaptive immunity. The Mediator complex forms the
      bridge between transcriptional activators and the general transcription
      machinery. Med1/TRAP220 (also called DRIP205) is a key component of Mediator that
      interacts with ligand-bound hormone receptors, such as the vitamin D receptor.
      Here, we show that T-cell-specific Med1 deficiency results in a specific block in
      iNKT cell development but the development of conventional alphabeta T cells
      remains grossly normal. The defect is cell-intrinsic and depends neither on
      apoptosis, cell-cycle control, nor on CD1d expression of CD4(+)CD8(+) double
      positive thymocytes. Surprisingly, ectopic expression of a Valpha14-Jalpha18 T
      cell receptor transgene completely rescues the defect caused by Med1 deficiency.
      At the molecular level, thymic iNKT cells in Med1(-/-) animals display reduced
      levels of IL-2Rbeta and T-bet expression and could not complete terminal
      maturation. Thus, Med1 is essential for a complete intrathymic development of
      iNKT cells.

PMID- 21949388
TI  - Habit learning is associated with major shifts in frequencies of oscillatory
      activity and synchronized spike firing in striatum.
AB  - Rhythmic brain activity is thought to reflect, and to help organize, spike
      activity in populations of neurons during on-going behavior. We report that
      during learning, a major transition occurs in task-related oscillatory activity
      in the ventromedial striatum, a striatal region related to motivation-dependent
      learning. Early on as rats learned a T-maze task, bursts of 70- to 90-Hz high
      gamma activity were prominent during T-maze runs, but these gradually receded as
      bursts of 15- to 28-Hz beta-band activity became pronounced. Populations of
      simultaneously recorded neurons synchronized their spike firing similarly during
      both the high-gamma-band and beta-band bursts. Thus, the structure of spike
      firing was reorganized during learning in relation to different rhythms. Spiking
      was concentrated around the troughs of the beta-oscillations for fast-spiking
      interneurons and around the peaks for projection neurons, indicating alternating
      periods of firing at different frequencies as learning progressed. Spike-field
      synchrony was primarily local during high-gamma-bursts but was widespread during
      beta-bursts. The learning-related shift in the probability of high-gamma and beta
      bursting thus could reflect a transition from a mainly focal rhythmic inhibition
      during early phases of learning to a more distributed mode of rhythmic inhibition
      as learning continues and behavior becomes habitual. These dynamics could
      underlie changing functions of the ventromedial striatum during habit formation.
      More generally, our findings suggest that coordinated changes in the
      spatiotemporal relationships of local field potential oscillations and spike
      activity could be hallmarks of the learning process.

PMID- 21949389
TI  - Exome sequencing identifies a spectrum of mutation frequencies in advanced and
      lethal prostate cancers.
AB  - To catalog protein-altering mutations that may drive the development of prostate
      cancers and their progression to metastatic disease systematically, we performed
      whole-exome sequencing of 23 prostate cancers derived from 16 different lethal
      metastatic tumors and three high-grade primary carcinomas. All tumors were
      propagated in mice as xenografts, designated the LuCaP series, to model
      phenotypic variation, such as responses to cancer-directed therapeutics. Although
      corresponding normal tissue was not available for most tumors, we were able to
      take advantage of increasingly deep catalogs of human genetic variation to remove
      most germline variants. On average, each tumor genome contained ~200 novel
      nonsynonymous variants, of which the vast majority was specific to individual
      carcinomas. A subset of genes was recurrently altered across tumors derived from
      different individuals, including TP53, DLK2, GPC6, and SDF4. Unexpectedly, three
      prostate cancer genomes exhibited substantially higher mutation frequencies, with
      2,000-4,000 novel coding variants per exome. A comparison of castration-resistant
      and castration-sensitive pairs of tumor lines derived from the same prostate
      cancer highlights mutations in the Wnt pathway as potentially contributing to the
      development of castration resistance. Collectively, our results indicate that
      point mutations arising in coding regions of advanced prostate cancers are common
      but, with notable exceptions, very few genes are mutated in a substantial
      fraction of tumors. We also report a previously undescribed subtype of prostate
      cancers exhibiting "hypermutated" genomes, with potential implications for
      resistance to cancer therapeutics. Our results also suggest that increasingly
      deep catalogs of human germline variation may challenge the necessity of
      sequencing matched tumor-normal pairs.

PMID- 21949390
TI  - Sir-two-homolog 2 (Sirt2) modulates peripheral myelination through polarity
      protein Par-3/atypical protein kinase C (aPKC) signaling.
AB  - The formation of myelin by Schwann cells (SCs) occurs via a series of
      orchestrated molecular events. We previously used global expression profiling to
      examine peripheral nerve myelination and identified the NAD(+)-dependent
      deacetylase Sir-two-homolog 2 (Sirt2) as a protein likely to be involved in
      myelination. Here, we show that Sirt2 expression in SCs is correlated with that
      of structural myelin components during both developmental myelination and
      remyelination after nerve injury. Transgenic mice lacking or overexpressing Sirt2
      specifically in SCs show delays in myelin formation. In SCs, we found that Sirt2
      deacetylates Par-3, a master regulator of cell polarity. The deacetylation of Par
      3 by Sirt2 decreases the activity of the polarity complex signaling component
      aPKC, thereby regulating myelin formation. These results demonstrate that Sirt2
      controls an essential polarity pathway in SCs during myelin assembly and provide
      insights into the association between intracellular metabolism and SC plasticity.

PMID- 21949391
TI  - Ancient host specificity within a single species of brood parasitic bird.
AB  - Parasites that exploit multiple hosts often experience diversifying selection for
      host-specific adaptations. This can result in multiple strains of host
      specialists coexisting within a single parasitic species. A long-standing
      conundrum is how such sympatric host races can be maintained within a single
      parasitic species in the face of interbreeding among conspecifics specializing on
      different hosts. Striking examples are seen in certain avian brood parasites such
      as cuckoos, many of which show host-specific differentiation in traits such as
      host egg mimicry. Exploiting a Zambian egg collection amassed over several
      decades and supplemented by recent fieldwork, we show that the brood parasitic
      Greater Honeyguide Indicator indicator exhibits host-specific differentiation in
      both egg size and egg shape. Genetic analysis of honeyguide eggs and chicks show
      that two highly divergent mitochondrial DNA lineages are associated with ground-
      and tree-nesting hosts, respectively, indicating perfect fidelity to two mutually
      exclusive sets of host species for millions of years. Despite their age and
      apparent adaptive diversification, however, these ancient lineages are not
      cryptic species; a complete lack of differentiation in nuclear genes shows that
      mating between individuals reared by different hosts is sufficiently frequent to
      prevent speciation. These results indicate that host specificity is maternally
      inherited, that host-specific adaptation among conspecifics can be maintained
      without reproductive isolation, and that host specificity can be remarkably
      ancient in evolutionary terms.

PMID- 21949392
TI  - More diverse plant communities have higher functioning over time due to turnover
      in complementary dominant species.
AB  - More diverse communities have been shown to have higher and more temporally
      stable ecosystem functioning than less diverse ones, suggesting they should also
      have a consistently higher level of functioning over time. Diverse communities
      could maintain consistently high function because the species driving function
      change over time (functional turnover) or because they are more likely to contain
      key species with temporally stable functioning. Across 7 y in a large
      biodiversity experiment, we show that more diverse plant communities had
      consistently higher productivity, that is, a higher level of functioning over
      time. We identify the mechanism for this as turnover in the species driving
      biomass production; this was substantial, and species that were rare in some
      years became dominant and drove function in other years. Such high turnover
      allowed functionally more diverse communities to maintain high biomass over time
      and was associated with higher levels of complementarity effects in these
      communities. In contrast, turnover in communities composed of functionally
      similar species did not promote high biomass production over time. Thus, turnover
      in species promotes consistently high ecosystem function when it sustains
      functionally complementary interactions between species. Our results strongly
      reinforce the argument for conservation of high biodiversity.

PMID- 21949393
TI  - Cooling the fires of inflammation.

PMID- 21949394
TI  - Evolution of the ocean's "biological pump".

PMID- 21949395
TI  - Cretaceous avian crops reveal dietary secrets and pose evolutionary questions.

PMID- 21949397
TI  - Targeting MYC dependence in cancer by inhibiting BET bromodomains.
AB  - The MYC transcription factor is a master regulator of diverse cellular functions
      and has been long considered a compelling therapeutic target because of its role
      in a range of human malignancies. However, pharmacologic inhibition of MYC
      function has proven challenging because of both the diverse mechanisms driving
      its aberrant expression and the challenge of disrupting protein-DNA interactions.
      Here, we demonstrate the rapid and potent abrogation of MYC gene transcription by
      representative small molecule inhibitors of the BET family of chromatin adaptors.
      MYC transcriptional suppression was observed in the context of the natural,
      chromosomally translocated, and amplified gene locus. Inhibition of BET
      bromodomain-promoter interactions and subsequent reduction of MYC transcript and
      protein levels resulted in G(1) arrest and extensive apoptosis in a variety of
      leukemia and lymphoma cell lines. Exogenous expression of MYC from an artificial
      promoter that is resistant to BET regulation significantly protected cells from
      cell cycle arrest and growth suppression by BET inhibitors. MYC suppression was
      accompanied by deregulation of the MYC transcriptome, including potent
      reactivation of the p21 tumor suppressor. Treatment with a BET inhibitor resulted
      in significant antitumor activity in xenograft models of Burkitt's lymphoma and
      acute myeloid leukemia. These findings demonstrate that pharmacologic inhibition
      of MYC is achievable through targeting BET bromodomains. Such inhibitors may have
      clinical utility given the widespread pathogenetic role of MYC in cancer.

PMID- 21949396
TI  - HSP90 functions in the circadian clock through stabilization of the client F-box
      protein ZEITLUPE.
AB  - The autoregulatory loops of the circadian clock consist of feedback regulation of
      transcription/translation circuits but also require finely coordinated
      cytoplasmic and nuclear proteostasis. Although protein degradation is important
      to establish steady-state levels, maturation into their active conformation also
      factors into protein homeostasis. HSP90 facilitates the maturation of a wide
      range of client proteins, and studies in metazoan clocks implicate HSP90 as an
      integrator of input or output. Here we show that the Arabidopsis circadian clock
      associated F-box protein ZEITLUPE (ZTL) is a unique client for cytoplasmic HSP90.
      The HSP90-specific inhibitor geldanamycin and RNAi-mediated depletion of
      cytoplasmic HSP90 reduces levels of ZTL and lengthens circadian period,
      consistent with ztl loss-of-function alleles. Transient transfection of
      artificial microRNA targeting cytoplasmic HSP90 genes similarly lengthens period.
      Proteolytic targets of SCF(ZTL), TOC1 and PRR5, are stabilized in geldanamycin
      treated seedlings, whereas the levels of closely related clock proteins, PRR3 and
      PRR7, are unchanged. An in vitro holdase assay, typically used to demonstrate
      chaperone activity, shows that ZTL can be effectively bound, and aggregation
      prevented, by HSP90. GIGANTEA, a unique stabilizer of ZTL, may act in the same
      pathway as HSP90, possibly linking these two proteins to a similar mechanism. Our
      findings establish maturation of ZTL by HSP90 as essential for proper function of
      the Arabidopsis circadian clock. Unlike metazoan systems, HSP90 functions here
      within the core oscillator. Additionally, F-box proteins as clients may place
      HSP90 in a unique and more central role in proteostasis.

PMID- 21949398
TI  - PI3Kgamma within a nonhematopoietic cell type negatively regulates diet-induced
      thermogenesis and promotes obesity and insulin resistance.
AB  - Obesity is associated with a chronic low-grade inflammation, and specific
      antiinflammatory interventions may be beneficial for the treatment of type 2
      diabetes and other obesity-related diseases. The lipid kinase PI3Kgamma is a
      central proinflammatory signal transducer that plays a major role in leukocyte
      chemotaxis, mast cell degranulation, and endothelial cell activation. It was also
      reported that PI3Kgamma activity within hematopoietic cells plays an important
      role in obesity-induced inflammation and insulin resistance. Here, we show that
      protection from insulin resistance, metabolic inflammation, and fatty liver in
      mice lacking functional PI3Kgamma is largely consequent to their leaner
      phenotype. We also show that this phenotype is largely based on decreased fat
      gain, despite normal caloric intake, consequent to increased energy expenditure.
      Furthermore, our data show that PI3Kgamma action on diet-induced obesity depends
      on PI3Kgamma activity within a nonhematopoietic compartment, where it promotes
      energetic efficiency for fat mass gain. We also show that metabolic modulation by
      PI3Kgamma depends on its lipid kinase activity and might involve kinase
      independent signaling. Thus, PI3Kgamma is an unexpected but promising drug target
      for the treatment of obesity and its complications.

PMID- 21949399
TI  - Regulatory elements required for the activation and repression of the
      protocadherin-alpha gene cluster.
AB  - The mouse protocadherin (Pcdh) -alpha, -beta, and -gamma gene clusters encode
      more than 50 protein isoforms, the combinatorial expression of which generates
      vast single-cell diversity in the brain. At present, the mechanisms by which this
      diversity is expressed are not understood. Here we show that two transcriptional
      enhancer elements, HS5-1 and HS7, play a critical role in Pcdhalpha gene
      expression in mice. We show that the HS5-1 element functions as an enhancer in
      neurons and a silencer in nonneuronal cells. The enhancer activity correlates
      with the binding of zinc finger DNA binding protein CTCF to the target promoters,
      and the silencer activity requires the binding of the REST/NRSF repressor complex
      in nonneuronal cells. Thus, the HS5-1 element functions as a neuron-specific
      enhancer and nonneuronal cell repressor. In contrast, the HS7 element functions
      as a Pcdhalpha cluster-wide transcription enhancer element. These studies reveal
      a complex organization of regulatory elements required for generating single cell
      Pcdh diversity.

PMID- 21949400
TI  - Separation of telomerase functions by reverse genetics.
AB  - The canonical function of the human telomerase protein (hTERT) is to synthesize
      telomeric DNA, but it has other biological activities, including enhancing cell
      proliferation, decreasing apoptosis, regulating DNA damage responses, and
      increasing cellular proliferative lifespan. The mechanistic relationships among
      these activities are not understood. We previously demonstrated that ectopic
      hTERT expression in primary human mammary epithelial cells diminishes their
      requirement for exogenous mitogens, thus giving them a proliferative advantage in
      a mitogen-depleted environment. Here, we show that this phenotype is caused by a
      combination of increased cell division and decreased apoptosis. In addition, we
      use a panel of hTERT mutants to demonstrate that this enhanced cell proliferation
      can be uncoupled not only from telomere elongation, but also from other
      telomerase activities, including cellular lifespan extension and regulation of
      DNA damage responses. We also find that the proliferative function of hTERT,
      which requires hTERT catalytic activity, is not caused by increased Wnt
      signaling, but is accompanied by alterations in key cell cycle regulators and is
      linked to an hTERT-catalyzed decrease in the levels of the RNA component of
      mitochondrial RNA processing endoribonuclease. Thus, enhanced cell proliferation
      is an independent function of hTERT that could provide a new target for the
      development of anti-telomerase cancer therapeutic agents.

PMID- 21949401
TI  - TrkB signaling in parvalbumin-positive interneurons is critical for gamma-band
      network synchronization in hippocampus.
AB  - Although brain-derived neurotrophic factor (BDNF) is known to regulate circuit
      development and synaptic plasticity, its exact role in neuronal network activity
      remains elusive. Using mutant mice (TrkB-PV(-/-)) in which the gene for the BDNF
      receptor, tyrosine kinase B receptor (trkB), has been specifically deleted in
      parvalbumin-expressing, fast-spiking GABAergic (PV+) interneurons, we show that
      TrkB is structurally and functionally important for the integrity of the
      hippocampal network. The amplitude of glutamatergic inputs to PV+ interneurons
      and the frequency of GABAergic inputs to excitatory pyramidal cells were reduced
      in the TrkB-PV(-/-) mice. Functionally, rhythmic network activity in the gamma
      frequency band (30-80 Hz) was significantly decreased in hippocampal area CA1.
      This decrease was caused by a desynchronization and overall reduction in
      frequency of action potentials generated in PV+ interneurons of TrkB-PV(-/-)
      mice. Our results show that the integration of PV+ interneurons into the
      hippocampal microcircuit is impaired in TrkB-PV(-/-) mice, resulting in decreased
      rhythmic network activity in the gamma-frequency band.

PMID- 21949402
TI  - Endothelial nitric oxide synthase controls the expression of the angiogenesis
      inhibitor thrombospondin 2.
AB  - Injury- and ischemia-induced angiogenesis is critical for tissue repair and
      requires nitric oxide (NO) derived from endothelial nitric oxide synthase (eNOS).
      We present evidence that NO induces angiogenesis by modulating the level of the
      angiogenesis inhibitor thrombospondin 2 (TSP2). TSP2 levels were higher than WT
      in eNOS KO tissues in hind-limb ischemia and cutaneous wounds. In vitro studies
      confirmed that NO represses TSP2 promoter activity. Moreover, double-eNOS/TSP2 KO
      mice were generated and found to rescue the phenotype of eNOS KO mice. Studies in
      mice with knock-in constitutively active or inactive eNOS on the Akt-1 KO
      background showed that eNOS activity correlates with TSP2 levels. Our
      observations of NO-mediated regulation of angiogenesis via the suppression of
      TSP2 expression provide a description of improved eNOS KO phenotype by means
      other than restoring NO signaling.

PMID- 21949403
TI  - Plasmodium ookinetes coopt mammalian plasminogen to invade the mosquito midgut.
AB  - Ookinete invasion of the mosquito midgut is an essential step for the development
      of the malaria parasite in the mosquito. Invasion involves recognition between a
      presumed mosquito midgut receptor and an ookinete ligand. Here, we show that
      enolase lines the ookinete surface. An antienolase antibody inhibits oocyst
      development of both Plasmodium berghei and Plasmodium falciparum, suggesting that
      enolase may act as an invasion ligand. Importantly, we demonstrate that surface
      enolase captures plasminogen from the mammalian blood meal via its lysine motif
      (DKSLVK) and that this interaction is essential for midgut invasion, because
      plasminogen depletion leads to a strong inhibition of oocyst formation. Although
      addition of recombinant WT plasminogen to depleted serum rescues oocyst
      formation, recombinant inactive plasminogen does not, thus emphasizing the
      importance of plasmin proteolytic activity for ookinete invasion. The results
      support the hypothesis that enolase on the surface of Plasmodium ookinetes plays
      a dual role in midgut invasion: by acting as a ligand that interacts with the
      midgut epithelium and, further, by capturing plasminogen, whose conversion to
      active plasmin promotes the invasion process.

PMID- 21949404
TI  - Inference of seed bank parameters in two wild tomato species using ecological and
      genetic data.
AB  - Seed and egg dormancy is a prevalent life-history trait in plants and
      invertebrates whose storage effect buffers against environmental variability,
      modulates species extinction in fragmented habitats, and increases genetic
      variation. Experimental evidence for reliable differences in dormancy over
      evolutionary scales (e.g., differences in seed banks between sister species) is
      scarce because complex ecological experiments in the field are needed to measure
      them. To cope with these difficulties, we developed an approximate Bayesian
      computation (ABC) framework that integrates ecological information on population
      census sizes in the priors of the parameters, along with a coalescent model
      accounting simultaneously for seed banks and spatial genetic structuring of
      populations. We collected SNP data at seven nuclear loci (over 300 SNPs) using a
      combination of three spatial sampling schemes: population, pooled, and species
      wide samples. We provide evidence for the existence of a seed bank in two wild
      tomato species (Solanum chilense and Solanum peruvianum) found in western South
      America. Although accounting for uncertainties in ecological data, we infer for
      each species (i) the past demography and (ii) ecological parameters, such as the
      germination rate, migration rates, and minimum number of demes in the
      metapopulation. The inferred difference in germination rate between the two
      species may reflect divergent seed dormancy adaptations, in agreement with
      previous population genetic analyses and the ecology of these two sister species:
      Seeds spend, on average, a shorter time in the soil in the specialist species (S.
      chilense) than in the generalist species (S. peruvianum).

PMID- 21949405
TI  - Identification of the bacterial protein FtsX as a unique target of chemokine
      mediated antimicrobial activity against Bacillus anthracis.
AB  - Chemokines are a family of chemotactic cytokines that function in host defense by
      orchestrating cellular movement during infection. In addition to this function,
      many chemokines have also been found to mediate the direct killing of a range of
      pathogenic microorganisms through an as-yet-undefined mechanism. As an
      understanding of the molecular mechanism and microbial targets of chemokine
      mediated antimicrobial activity is likely to lead to the identification of
      unique, broad-spectrum therapeutic targets for effectively treating infection, we
      sought to investigate the mechanism by which the chemokine CXCL10 mediates
      bactericidal activity against the Gram-positive bacterium Bacillus anthracis, the
      causative agent of anthrax. Here, we report that disruption of the gene ftsX,
      which encodes the transmembrane domain of a putative ATP-binding cassette
      transporter, affords resistance to CXCL10-mediated antimicrobial effects against
      vegetative B. anthracis bacilli. Furthermore, we demonstrate that in the absence
      of FtsX, CXCL10 is unable to localize to its presumed site of action at the
      bacterial cell membrane, suggesting that chemokines interact with specific,
      identifiable bacterial components to mediate direct microbial killing. These
      findings provide unique insight into the mechanism of CXCL10-mediated
      bactericidal activity and establish, to our knowledge, the first description of a
      bacterial component critically involved in the ability of host chemokines to
      target and kill a bacterial pathogen. These observations also support the notion
      of chemokine-mediated antimicrobial activity as an important foundation for the
      development of innovative therapeutic strategies for treating infections caused
      by pathogenic, potentially multidrug-resistant microorganisms.

PMID- 21949409
TI  - Drug solubilization effect of lauroyl-L-glutamate.
AB  - This article proposes a new technique for the solubilization of poorly soluble
      drugs using lauroyl-L-glutamate, which is one of the amino acid detergents, with
      additional small additives. Lauroyl-L-glutamate was highly effective in
      solubilizing long-chain alkyl gallates, e.g. dodecyl gallate. Furthermore,
      lauroyl-L-glutamate and small additives, particularly arginine, acted to increase
      the solubility of alkyl gallates. The synergistic effect was not observed by
      sodium dodecyl sulphate with arginine. The solubilizing system can be applied to
      other drugs because of the low toxicity of both lauroyl-L-glutamate and arginine.

PMID- 21949408
TI  - Tumor suppressor protein (p)53, is a regulator of NF-kappaB repression by the
      glucocorticoid receptor.
AB  - Glucocorticoids can inhibit inflammation by abrogating the activity of NF-kappaB,
      a family of transcription factors that regulates the production of
      proinflammatory cytokines. To understand the molecular mechanism of repression of
      NF-kappaB activity by glucocorticoids, we performed a high-throughput siRNA oligo
      screen to identify novel genes involved in this process. Here, we report that
      loss of p53, a tumor suppressor protein, impaired repression of NF-kappaB target
      gene transcription by glucocorticoids. Additionally, loss of p53 also impaired
      transcription of glucocorticoid receptor (GR) target genes, whereas upstream NF
      kappaB and glucocorticoid receptor signaling cascades remained intact. We further
      demonstrate that p53 loss severely impaired glucocorticoid rescue of death in a
      mouse model of LPS shock. Our findings unveil a new role for p53 in the
      repression of NF-kappaB by glucocorticoids and suggest important implications for
      treatment of the proinflammatory microenvironments found in tumors with aberrant
      p53 activity.

PMID- 21949411
TI  - Transmembrane segments of nascent polytopic membrane proteins control cytosol/ER
      targeting during membrane integration.
AB  - During cotranslational integration of a eukaryotic multispanning polytopic
      membrane protein (PMP), its hydrophilic loops are alternately directed to
      opposite sides of the ER membrane. Exposure of fluorescently labeled nascent PMP
      to the cytosol or ER lumen was detected by collisional quenching of its
      fluorescence by iodide ions localized in the cytosol or lumen. PMP loop exposure
      to the cytosol or lumen was controlled by structural rearrangements in the
      ribosome, translocon, and associated proteins that occurred soon after a nascent
      chain transmembrane segment (TMS) entered the ribosomal tunnel. Each successive
      TMS, although varying in length, sequence, hydrophobicity, and orientation,
      reversed the structural changes elicited by its predecessor, irrespective of loop
      size. Fluorescence lifetime data revealed that TMSs occupied a more nonpolar
      environment than secretory proteins inside the aqueous ribosome tunnel, which
      suggests that TMS recognition by the ribosome involves hydrophobic interactions.
      Importantly, the TMS-triggered structural rearrangements that cycle nascent chain
      exposure between cytosolic and lumenal occur without compromising the
      permeability barrier of the ER membrane.

PMID- 21949410
TI  - Polytopic membrane protein folding at L17 in the ribosome tunnel initiates
      cyclical changes at the translocon.
AB  - Multi-spanning membrane protein loops are directed alternately into the cytosol
      or ER lumen during cotranslational integration. Nascent chain exposure is
      switched after a newly synthesized transmembrane segment (TMS) enters the
      ribosomal tunnel. FRET measurements revealed that each TMS is initially extended,
      but folds into a compact conformation after moving 6-7 residues from the
      peptidyltransferase center, irrespective of loop size. The ribosome-induced
      folding of each TMS coincided with its photocrosslinking to ribosomal protein L17
      and an inversion of compartmental exposure. This correlation indicates that
      successive TMSs fold and bind at a specific ribosomal tunnel site that includes
      L17, thereby triggering structural rearrangements of multiple components in and
      on both sides of the ER membrane, most likely via TMS-dependent L17 and/or rRNA
      conformational changes transmitted to the surface. Thus, cyclical changes at the
      membrane during integration are initiated by TMS folding, even though nascent
      chain conformation and location vary dynamically in the ribosome tunnel. Nascent
      chains therefore control their own trafficking.

PMID- 21949412
TI  - EMILIN1-alpha4/alpha9 integrin interaction inhibits dermal fibroblast and
      keratinocyte proliferation.
AB  - EMILIN1 promotes alpha4beta1 integrin-dependent cell adhesion and migration and
      reduces pro-transforming growth factor-beta processing. A knockout mouse model
      was used to unravel EMILIN1 functions in skin where the protein was abundantly
      expressed in the dermal stroma and where EMILIN1-positive fibrils reached the
      basal keratinocyte layer. Loss of EMILIN1 caused dermal and epidermal
      hyperproliferation and accelerated wound closure. We identified the direct
      engagement of EMILIN1 to alpha4beta1 and alpha9beta1 integrins as the mechanism
      underlying the homeostatic role exerted by EMILIN1. The lack of EMILIN1
      alpha4/alpha9 integrin interaction was accompanied by activation of PI3K/Akt and
      Erk1/2 pathways as a result of the reduction of PTEN. The down-regulation of PTEN
      empowered Erk1/2 phosphorylation that in turn inhibited Smad2 signaling by
      phosphorylation of residues Ser245/250/255. These results highlight the important
      regulatory role of an extracellular matrix component in skin proliferation. In
      addition, EMILIN1 is identified as a novel ligand for keratinocyte alpha9beta1
      integrin, suggesting prospective roles for this receptor-ligand pair in skin
      homeostasis.

PMID- 21949413
TI  - Abcg2 labels multiple cell types in skeletal muscle and participates in muscle
      regeneration.
AB  - Skeletal muscle contains progenitor cells (satellite cells) that maintain and
      repair muscle. It also contains muscle side population (SP) cells, which express
      Abcg2 and may participate in muscle regeneration or may represent a source of
      satellite cell replenishment. In Abcg2-null mice, the SP fraction is lost in
      skeletal muscle, although the significance of this loss was previously unknown.
      We show that cells expressing Abcg2 increased upon injury and that muscle
      regeneration was impaired in Abcg2-null mice, resulting in fewer centrally
      nucleated myofibers, reduced myofiber size, and fewer satellite cells.
      Additionally, using genetic lineage tracing, we demonstrate that the progeny of
      Abcg2-expressing cells contributed to multiple cell types within the muscle
      interstitium, primarily endothelial cells. After injury, Abcg2 progeny made a
      minor contribution to regenerated myofibers. Furthermore, Abcg2-labeled cells
      increased significantly upon injury and appeared to traffic to muscle from
      peripheral blood. Together, these data suggest an important role for Abcg2 in
      positively regulating skeletal muscle regeneration.

PMID- 21949416
TI  - Abuse history, depression, and somatization are associated with gastric
      sensitivity and gastric emptying in functional dyspepsia.
AB  - OBJECTIVE: Gastric sensitivity testing relies on subjective reporting and may
      therefore be influenced by psychosocial factors and somatization. Furthermore,
      psychological processes may affect gastric motor function (accommodation to a
      meal emptying) through efferent brain-gut pathways. This study sought to
      determine the association of abuse history, psychiatric comorbidity, and
      somatization with gastric sensorimotor function. METHODS: In 201 patients with
      functional dyspepsia, gastric sensitivity and accommodation were studied with a
      barostat. Gastric emptying of solids was studied using a breath test. Sexual and
      physical abuse history, psychiatric comorbidity (depression and panic disorder),
      and somatization were assessed using validated questionnaires. Multiple linear
      regression models were used to identify patient characteristics independently
      associated with gastric sensitivity and emptying. RESULTS: Age (p = .02), sexual
      abuse history (p < .001), physical abuse history (p = .004), and somatization (p
      < .001) were independently associated with gastric discomfort threshold (R(2) =
      0.30); a significant depression-by-sexual abuse interaction effect was also found
      (p = .003). None of the factors studied were associated with gastric
      accommodation to a meal. Physical abuse history (p = .003) and somatization (p =
      .048) were independently associated with gastric emptying (R(2) = 0.19).
      CONCLUSIONS: These results demonstrate the complex relationship among abuse
      history, psychiatric comorbidity, somatization, and gastric sensorimotor
      (dys)function. Although the psychobiological mechanisms underlying these
      relationships remain to be determined, the autonomic nervous, stress hormone, and
      immune systems may be involved.

PMID- 21949415
TI  - Actin and microtubules drive differential aspects of planar cell polarity in
      multiciliated cells.
AB  - Planar cell polarization represents the ability of cells to orient within the
      plane of a tissue orthogonal to the apical basal axis. The proper polarized
      function of multiciliated cells requires the coordination of cilia spacing and
      cilia polarity as well as the timing of cilia beating during metachronal
      synchrony. The planar cell polarity pathway and hydrodynamic forces have been
      shown to instruct cilia polarity. In this paper, we show how intracellular
      effectors interpret polarity to organize cellular morphology in accordance with
      asymmetric cellular function. We observe that both cellular actin and microtubule
      networks undergo drastic reorganization, providing differential roles during the
      polarized organization of cilia. Using computational angular correlation analysis
      of cilia orientation, we report a graded cellular organization downstream of cell
      polarity cues. Actin dynamics are required for proper cilia spacing, global
      coordination of cilia polarity, and coordination of metachronic cilia beating,
      whereas cytoplasmic microtubule dynamics are required for local coordination of
      polarity between neighboring cilia.

PMID- 21949414
TI  - Stress-responsive maturation of Clk1/4 pre-mRNAs promotes phosphorylation of SR
      splicing factor.
AB  - It has been assumed that premessenger ribonucleic acids (RNAs; pre-mRNAs) are
      spliced cotranscriptionally in the process of gene expression. However, in this
      paper, we report that splicing of Clk1/4 mRNAs is suspended in tissues and
      cultured cells and that intermediate forms retaining specific introns are
      abundantly pooled in the nucleus. Administration of the Cdc2-like kinase-specific
      inhibitor TG003 increased the level of Clk1/4 mature mRNAs by promoting splicing
      of the intron-retaining RNAs. Under stress conditions, splicing of general pre
      mRNAs was inhibited by dephosphorylation of SR splicing factors, but exposure to
      stresses, such as heat shock and osmotic stress, promoted the maturation of
      Clk1/4 mRNAs. Clk1/4 proteins translated after heat shock catalyzed
      rephosphorylation of SR proteins, especially SRSF4 and SRSF10. These findings
      suggest that Clk1/4 expression induced by stress-responsive splicing serves to
      maintain the phosphorylation state of SR proteins.

PMID- 21949418
TI  - Self-reported versus other-reported distress and coronary artery calcification.

PMID- 21949417
TI  - Optimism in relation to inflammation and endothelial dysfunction in older men:
      the VA Normative Aging Study.
AB  - BACKGROUND: Recent research suggests that optimism may reduce the risk of
      incident cardiovascular disease, but the mechanisms have not been determined.
      This study examines the association of optimism with change in inflammation and
      endothelial function over time in men. METHODS: Longitudinal data were obtained
      from the Normative Aging Study excluding men with preexisting coronary heart
      disease or active infection at the time optimism was assessed (n = 340; mean
      [standard deviation] age = 70.9 [6.7] years). The Life Orientation Test was used
      to measure optimism, and serum markers were used to measure inflammation and
      endothelial dysfunction and were obtained repeatedly during the course of the
      study (1999-2008). These markers included high-sensitivity C-reactive protein,
      interleukin 6, soluble intercellular adhesion molecule 1, soluble vascular cell
      adhesion molecule 1, and soluble tumor necrosis factor receptor II. Within this
      sample, 243 men (71%) had two or more repeated measures of each outcome,
      resulting in a total of 746 observations for analysis. Linear mixed-effects
      models with a random subject intercept were used to estimate associations.
      RESULTS: Higher overall optimism scores were associated with lower levels of
      interleukin 6 and soluble intercellular adhesion molecule 1 pooled across
      multiple time points in multivariable models but were not associated with rate of
      change in these markers over time. Analyses considering separate effects of
      optimism and pessimism subscales with each outcome indicated stronger effects of
      a pessimistic orientation versus an optimistic orientation. CONCLUSIONS: Higher
      overall optimism scores were associated with lower levels of inflammation and
      endothelial dysfunction in older men free of coronary heart disease.

PMID- 21949419
TI  - Generalized anxiety disorder is associated with reduced lung function in the
      Vietnam Experience Study.
AB  - BACKGROUND: There is no clear consensus in the few studies to have explored the
      relationship between major mental health disorders and lung function. The present
      study examined the cross-sectional associations of generalized anxiety disorder
      (GAD) and major depressive disorder (MDD) with lung function in a large study of
      male US veterans. METHODS: Participants (N = 4256) were drawn from the Vietnam
      Experience Study. From military files, telephone interviews, and a medical
      examination, anthropometric, sociodemographic, and health data were collected.
      One-year prevalence of GAD and MDD was determined using DSM-III criteria. Forced
      expiratory volume in 1 second was measured by spirometry. RESULTS: In models that
      adjusted for age and height, both GAD (p < .001) and MDD (p = .004) were
      associated with lower forced expiratory volume in 1 second. In models
      additionally adjusting for weight, place of service, ethnicity, marriage,
      smoking, alcohol consumption, income, education, and major illness, GAD was still
      associated with poorer lung function (p = .01), whereas MDD was not (p = .18).
      CONCLUSIONS: Depression has very much been the focus of studies on mental health
      and physical health status. The current findings suggest that future research
      should perhaps pay equal attention to GAD.

PMID- 21949420
TI  - Pain-related emotions in early stages of recovery in whiplash-associated
      disorders: their presence, intensity, and association with pain recovery.
AB  - OBJECTIVE: Psychological factors such as depression affect recovery after
      whiplash-associated disorders. This study examined the prevalence of pain-related
      emotions, such as frustration, anger, and anxiety, and their predictive value for
      postcrash pain recovery during a 1-year follow-up. METHODS: A population-based
      prospective cohort study design was used. Self-reported pain-related depression,
      anxiety, fear, anger, and frustration were assessed using 100-mm visual analog
      scales (VASs) at 6 weeks after crash in 2986 persons with traffic-related
      whiplash-associated disorder. Multivariable logistic regression was used to
      assess the relationship between the intensity of these pain-related emotions and
      pain recovery at 4 and 12 months after crash. Pain was measured at all time
      points on a 100-mm VAS, and pain recovery was defined as a score of 10 or lower.
      RESULTS: Pain-related frustration was the most intense, with a mean score of 52.
      Only 3% of the cohort reported having no pain-related frustration, and 4%
      reported no pain-related anxiety. Multivariable logistic regression models
      revealed that each pain-related emotion increased the risk of failing to recover
      (odds ratios for each point increase on the 100-mm VAS), ranging from 1.011 to
      1.015. Specifically, with each 10-point increase in pain-related emotion, the
      odds of failing to achieve pain recovery at 4 months was increased by 14% (p <
      .001) for depression, 15% (p < .001) for anxiety, 11% (p < .001) for fear, 12% (p
      < .001) for anger, and 11% (p < .001) for frustration. CONCLUSIONS: These
      findings suggest that it may be beneficial for health care providers to address
      emotional status related to pain in the first few weeks after a whiplash injury.

PMID- 21949421
TI  - Testosterone in newly diagnosed, antipsychotic-naive men with nonaffective
      psychosis: a test of the accelerated aging hypothesis.
AB  - OBJECTIVE: Schizophrenia has been associated with age-related abnormalities,
      including abnormal glucose tolerance, increased pulse pressure, increased
      inflammation, abnormal stem cell signaling, and shorter telomere length. These
      metabolic abnormalities and other findings suggest that schizophrenia and related
      disorders might be associated with accelerated aging. Testosterone activity has a
      progressive decline with increasing age. METHODS: We tested the hypothesis that
      circulating biologically active testosterone is lower in newly diagnosed,
      antipsychotic-naive male patients with nonaffective psychosis than in matched
      control subjects. RESULTS: Patients (n = 33) were matched to control subjects (n
      = 33) for age, sex, body mass index, socioeconomic status of the family of
      origin, and smoking. The free androgen index, a measure of biologically active
      testosterone, was significantly lower in the psychosis group (mean [standard
      deviation] = 57.7% [26.1]) than in control subjects (71.6% [27.0], p = .04), with
      an effect size of 0.53. Multivariate analysis also supported the findings. In the
      psychosis group, free androgen index had a significant negative correlation with
      the conceptual disorganization item (r = -0.35, p = .049) but not with reality
      distortion (r = -0.21, p = .24), negative symptoms (r = 0.004, p = .98), or
      depression (r = -0.014, p = .94). CONCLUSIONS: Lower testosterone level is
      consistent with accelerated aging in nonaffective psychosis, but further testing
      of this hypothesis is needed.

PMID- 21949422
TI  - Cardiovascular reactivity to acute psychological stress following sleep
      deprivation.
AB  - OBJECTIVE: Psychological stress and sleep disturbances are highly prevalent and
      are both implicated in the etiology of cardiovascular diseases. Given the common
      co-occurrence of psychological distress and sleep disturbances including short
      sleep duration, this study examined the combined effects of these two factors on
      blood pressure reactivity to immediate mental challenge tasks after well-rested
      and sleep-deprived experimental conditions. METHODS: Participants (n = 20) were
      healthy young adults free from current or past sleep, psychiatric, or major
      medical disorders. Using a within-subjects crossover design, we examined acute
      stress reactivity under two experimental conditions: after a night of normal
      sleep in the laboratory and after a night of total sleep deprivation. Two
      standardized psychological stress tasks were administered, a Stroop color-word
      naming interference task and a speech task, which were preceded by a prestress
      baseline period and followed by a poststress recovery period. Each period was 10
      minutes in duration, and blood pressure recordings were collected every 2.5
      minutes throughout each period. Mean blood pressure responses during stress and
      recovery periods were examined with a mixed-effects analysis of covariance,
      controlling for baseline blood pressure. RESULTS: There was a significant
      interaction between sleep deprivation and stress on systolic blood pressure
      (F(2,82.7) = 4.05, p = .02). Systolic blood pressure was higher in the sleep
      deprivation condition compared with the normal sleep condition during the speech
      task and during the two baseline periods. CONCLUSIONS: Sleep deprivation
      amplified systolic blood pressure increases to psychological stress. Sleep loss
      may increase cardiovascular risk by dysregulating stress physiology.

PMID- 21949425
TI  - Harm avoidance and risk of Alzheimer's disease.
AB  - OBJECTIVE: To test the hypothesis that harm avoidance, a trait associated with
      behavioral inhibition, is associated with the risk of developing Alzheimer's
      disease (AD). METHODS: A total of 791 adults 55 years and older without dementia
      completed a standard self-report measure of harm avoidance. They then underwent
      annual evaluations that included detailed cognitive testing and clinical
      classification of mild cognitive impairment (MCI), dementia, and AD. In a uniform
      neuropathologic examination of those who died, counts of neuritic plaques,
      diffuse plaques, and neurofibrillary tangles were standardized and combined to
      yield a pathologic measure of disease. The relation of harm avoidance to
      incidence of AD and related outcomes was estimated in analyses adjusted for age,
      sex, and education. RESULTS: During a mean of 3.5 years of annual observation, 98
      people (12.4%) developed incident AD. A high level of harm avoidance (90th
      percentile) was associated with a more than two-fold increase in risk of AD
      compared with a low score (10th percentile). Higher harm avoidance was also
      associated with increased incidence of MCI and more rapid decline in episodic
      memory, working memory, and perceptual speed (but not semantic memory or
      visuospatial ability). In 116 participants who died and underwent brain autopsy,
      harm avoidance was not related to a composite measure of plaques and tangles.
      CONCLUSIONS: A high level of the harm avoidance trait, indicating a tendency
      toward behavioral inhibition, is related to the risk of developing AD and its
      precursor, MCI.

PMID- 21949424
TI  - Psychiatric symptoms and proinflammatory cytokines in pregnancy.
AB  - OBJECTIVE: Clinical studies suggest that psychiatric symptoms, particularly
      depression, anxiety, and trauma, may be associated with inflammation, as indexed
      by proinflammatory cytokines. Such a link may be especially significant in
      pregnancy and may shed additional light on the etiology of perinatal mood
      disorders. METHODS: We prospectively observed 145 women selected from a community
      obstetric clinic serving a primarily low-income, high-psychosocial risk
      population. Women without evidence of medical high-risk pregnancies were screened
      (including psychiatric and trauma histories) and then assessed in detail (e.g.,
      mood symptoms) at approximately 18 and 32 weeks' gestation. Blood was drawn to
      measure key proinflammatory markers, interleukin 6 and tumor necrosis factor
      alpha (TNF-alpha). Data on pregnancy and obstetric outcome were derived from
      medical records. RESULTS: There was considerable stability of cytokine levels
      within individuals and a significant mean increase across pregnancy observed for
      interleukin 6 (p < .001) and TNF-alpha (p < .001). History of trauma was
      associated with significantly elevated TNF-alpha levels (F(1,135) = 4.43, p <
      .05), controlling for psychosocial and obstetric covariates. In contrast,
      elevated measures of depression and anxiety were unrelated to proinflammatory
      cytokines (p > .1). Exploratory analyses indicated that neither psychiatric
      symptoms nor proinflammatory cytokines predicted birth weight, gestational age,
      or obstetric complications. CONCLUSIONS: These findings suggest that antecedent
      trauma may be associated with persistently elevated TNF-alpha levels during
      pregnancy. The evidence that a generalized proinflammatory state was associated
      with symptoms of depression or anxiety in pregnant women was not found.

PMID- 21949426
TI  - Associations of trait optimism with diurnal neuroendocrine activity, cortisol
      responses to mental stress, and subjective stress measures in healthy men and
      women.
AB  - OBJECTIVE: To examine the associations of dispositional optimism with diurnal
      salivary cortisol, cortisol responses to standardized laboratory stress, and task
      induced subjective stress and control in a sample of individuals 53 years and
      older. METHODS: Five hundred forty-three healthy men and women (mean [standard
      deviation] age, 62.9 [5.7] years) attended a psychophysiological stress session
      and provided five salivary cortisol samples during a normal day. During the
      stress testing session, cortisol responses to two behavioral tasks were assessed.
      The associations of dispositional optimism with cortisol and subjective appraisal
      were assessed using hierarchical multiple regression analysis. RESULTS: The
      cortisol awakening response, but not the diurnal profile, was negatively
      associated with optimism independently of age, sex, employment grade, body mass
      index, smoking status, depressive symptoms, and time of awakening (beta = -0.12,
      p <= .05). No associations were observed between optimism and stress-induced
      cortisol changes in the laboratory; however, perceived stress was lower (beta = 
      0.18, p <= .001), and perception of control was higher (beta = 0.18, p <= .001),
      in more optimistic participants during the psychophysiological testing session.
      CONCLUSIONS: Dispositional optimism may confer benefits to the individual through
      attenuated hypothalamic-pituitary-adrenal axis response to waking in everyday
      life. However, no evidence emerged for an association between optimism and
      cortisol laboratory stress responses, which suggests that other compensatory
      mechanisms might play a role.

PMID- 21949427
TI  - Neuroticism, depressive symptoms, and serum BDNF.
AB  - OBJECTIVE: Animal models and clinical studies suggest that brain-derived
      neurotrophic factor (BDNF) is involved in the pathophysiology of depression. We
      test whether serum and plasma levels of BDNF are associated with trait
      neuroticism and its facets and with state measures of depressive symptoms.
      METHODS: In a community-based cohort (N = 2099), we measured serum and plasma
      BDNF concentrations and administered the Revised NEO Personality Inventory and
      the Center for Epidemiological Studies Depression Scale. Covariates included age,
      sex, cigarette smoking, obesity, and antidepressant use. RESULTS: Serum BDNF
      concentrations were inversely related to neuroticism (r = -0.074, p < .001), in
      particular the depression facet (r = -0.08, p < .001). Lower BDNF concentrations
      were also associated with severe depressive symptoms (Center for Epidemiological
      Studies Depression Scale >= 28; odds ratio = 0.906; 95% confidence interval =
      0.851-0.965). The association of serum BDNF with neuroticism was independent of
      depressive symptoms, indicating that serum BDNF might represent a biological
      correlate of neuroticism and not just of transient depressive states. Plasma BDNF
      was not associated with measures of depression. CONCLUSIONS: Our study suggests
      that lower serum BDNF is associated with both a dispositional vulnerability to
      depression and acute depressive states in the general population.

PMID- 21949430
TI  - Assessing longitudinal change in coordination of the paretic upper limb using on
      site 3-dimensional kinematic measurements.
AB  - BACKGROUND AND PURPOSE: It is largely unknown how adaptive motor control of the
      paretic upper limb contributes to functional recovery after stroke. This paucity
      of knowledge emphasizes the need for longitudinal 3-dimensional (3D) kinematic
      studies with frequent measurements to establish changes in coordination after
      stroke. A portable 3D kinematic setup would facilitate the frequent follow-up of
      people poststroke. This case report shows how longitudinal kinematic changes of
      the upper limb can be measured at a patient's home using a portable 3D kinematic
      system in the first 6 months poststroke. CASE DESCRIPTION: The outcomes of the
      upper-limb section of the Fugl-Meyer Motor Assessment (FMA), the Action Research
      Arm Test (ARAT), and 3D kinematic analyses were obtained from a 41-year-old man
      with a left hemispheric stroke. Three-dimensional kinematic data of the paretic
      upper limb were collected during a reach-to-grasp task using a portable motion
      tracker in 5 measurements during the first 6 months after stroke. Data from an
      individual who was healthy were used for comparison. OUTCOMES: The FMA and ARAT
      scores showed nonlinear recovery profiles, accompanied by significant changes in
      kinematic outcomes over time poststroke. Specifically, elbow extension increased,
      forward trunk motion decreased, peak hand speed increased, peak hand opening
      increased, and peak hand opening occurred sooner after peak hand speed.
      DISCUSSION: This case report illustrates the feasibility of frequently repeated,
      on-site 3D kinematic measurements of the paretic upper limb. Early after stroke,
      task performance was mainly driven by adaptive motor control, whereas adaptations
      were mostly reduced at 26 weeks poststroke. The presented approach allows the
      investigation of what is changing in coordination and how these changes are
      related to the nonlinear pattern of improvements in body functions and activities
      after stroke.

PMID- 21949429
TI  - Medical comorbidity of full and partial posttraumatic stress disorder in US
      adults: results from Wave 2 of the National Epidemiologic Survey on Alcohol and
      Related Conditions.
AB  - OBJECTIVE: This study examined associations between lifetime trauma exposures,
      PTSD and partial PTSD, and past-year medical conditions in a nationally
      representative sample of US adults. METHODS: Face-to-face interviews were
      conducted with 34,653 participants in the Wave 2 National Epidemiologic Survey on
      Alcohol and Related Conditions. Logistic regression analyses evaluated
      associations of trauma exposure, PTSD, and partial PTSD with respondent-reported
      medical diagnoses. RESULTS: After adjustment for sociodemographic characteristics
      and comorbid Axis I and II disorders, respondents with full PTSD were more likely
      than traumatized respondents without full or partial PTSD (comparison group) to
      report diagnoses of diabetes mellitus, noncirrhotic liver disease, angina
      pectoris, tachycardia, hypercholesterolemia, other heart disease, stomach ulcer,
      human immunodeficiency virus seropositivity, gastritis, and arthritis (odds
      ratios [ORs] = 1.2-2.5). Respondents with partial PTSD were more likely than the
      comparison group to report past-year diagnoses of stomach ulcer, angina pectoris,
      tachycardia, and arthritis (ORs = 1.3-1.6). Men with full and partial PTSD were
      more likely than controls to report diagnoses of hypertension (both ORs = 1.6),
      and both men and women with PTSD (OR = 1.8 and OR = 1.6, respectively) and men
      with partial PTSD (OR = 2.0) were more likely to report gastritis. The total
      number of lifetime traumatic event types was associated with many assessed
      medical conditions (ORs = 1.04-1.16), reducing the magnitudes and rendering some
      of the associations between PTSD status and medical conditions nonsignificant.
      CONCLUSIONS: Greater lifetime trauma exposure and PTSD are associated with
      numerous medical conditions, many of which are stress-related and chronic, in US
      adults. Partial PTSD is associated with intermediate odds of some of these
      conditions.

PMID- 21949428
TI  - Sex differences in the association of Framingham Cardiac Risk Score with
      cognitive decline in community-dwelling elders without clinical heart disease.
AB  - OBJECTIVE: To investigate a possible link between cardiovascular risk factors and
      age-related cognitive decline, the association of the 1998 Framingham Cardiac
      Risk Score (FCRS) with the trajectory of cognitive function test (CFT)
      performance over an 18 year period was examined in adults 50 years and older
      without clinical heart disease at baseline. METHODS: Participants were 985 men
      and women who had assessments of cognitive function at 3- to 4-year intervals.
      The association of FCRS category with CFT score trajectory was examined using
      mixed-effects models stratified by sex and controlling for age, educational
      level, and number of successive cognitive assessments. RESULTS: At baseline,
      median FCRS corresponded to a 14% risk of a coronary heart disease event within
      10 years for men and an 8% risk for women; 31% of men and 6% of women were at
      high (>20%) risk. In longitudinal analyses, women with FCRS risk higher than 7%
      had a higher rate of decline on tests of verbal fluency (p values < .05) and long
      term recall (p values < .01) compared with low-risk women; modest, but
      significant (p values < .05), differences in the trajectory of Mini-Mental State
      Examination and Trail-Making Test B scores were also apparent. FCRS category was
      not related to the rate of decline in CFT performance in men. CONCLUSIONS: For
      older women, very low levels of risk of coronary heart disease were associated
      with preservation of cognitive function for 10 years, suggesting that the
      maintenance of cardiovascular health may slow cognitive decline. The minimal
      association in men, who were at higher baseline risk, may be due to the selective
      attrition of men with greater cognitive decline.

PMID- 21949431
TI  - Management of sternal precautions following median sternotomy by physical
      therapists in Australia: a web-based survey.
AB  - BACKGROUND: Sternal precautions are utilized within many hospitals with the aim
      of preventing the occurrence of sternal complications (eg, infection, wound
      breakdown) following midline sternotomy. The evidence base for sternal precaution
      protocols, however, has been questioned due to a paucity of research, unknown
      effect on patient outcomes, and possible discrepancies in pattern of use among
      institutions. OBJECTIVE: The objective of this study was to investigate and
      document the use of sternal precautions by physical therapists in the treatment
      of patients following median sternotomy in hospitals throughout Australia, from
      immediately postsurgery to discharge from the hospital. DESIGN: A cross
      sectional, observational design was used. An anonymous, Web-based survey was
      custom designed for use in the study. METHODS: The questionnaire was content
      validated, and the online functionality was assessed. The senior cardiothoracic
      physical therapist from each hospital identified as currently performing
      cardiothoracic surgery (N=51) was invited to participate. RESULTS: The response
      rate was 58.8% (n=30). Both public (n=18) and private (n=12) hospitals in all
      states of Australia were represented. Management protocols reported by
      participants included wound support (n=22), restrictions on lifting and transfers
      (n=23), and restrictions on mobility aid use (n=15). Factors influencing clinical
      practice most commonly included "workplace practices/protocols" (n=27) and
      "clinical experience" (n=22). Limitations The study may be limited by response
      bias. CONCLUSIONS: Significant variation exists in the sternal precautions and
      protocols used in the treatment of patients following median sternotomy in
      Australian hospitals. Further research is needed to investigate whether the
      restrictions and precautions used are necessary and whether protocols have an
      impact on patient outcomes, including rates of recovery and length of stay.

PMID- 21949432
TI  - Pulsatile lavage for the enhancement of pressure ulcer healing: a randomized
      controlled trial.
AB  - BACKGROUND: Pressure ulcer development is a common, serious complication after
      spinal cord injury (SCI). Although many biophysical agents are available for
      treatment, few randomized controlled trials of their efficacy have been done.
      OBJECTIVE: The study objective was to examine the efficacy of low-pressure
      pulsatile lavage treatment for stage III and IV pressure ulcers in people with
      SCI. DESIGN: This study was a randomized controlled trial. Participants and
      assessors were unaware of intervention assignments. SETTING: This study was
      conducted in an SCI tertiary care center inpatient unit. PARTICIPANTS:
      Participants were 28 people with SCI and stage III and IV pelvic pressure ulcers;
      14 participants each were randomly assigned to treatment and control (sham
      treatment) groups. INTERVENTION: Daily low-pressure pulsatile lavage treatment
      with 1 L of normal saline at 11 psi of pressure was applied to the treatment
      group along with standard dressing changes. The control group received only sham
      treatment and standard dressing changes. MEASUREMENTS: Linear and volume
      measurements of pressure ulcer dimensions were obtained weekly for 3 weeks.
      RESULTS: Statistical analysis with the t test revealed no statistically
      significant difference in demographics between groups. Random-coefficient models
      for analysis of linear and volume measurements revealed improvements over time
      for both groups. Time trend analysis revealed greater measurement decreases for
      the treatment group. Differences in rates of change (with 95% confidence
      intervals) for treatment and control groups, respectively, were: depth, -0.24
      (0.09 to -0.58) cm/wk; width, -0.16 (0.06 to -0.39) cm/wk; length, -0.47 (0.18 to
      -1.12) cm/wk; and volume, -0.33 (0.13 to -0.80) cm(3)/wk. LIMITATIONS: Study
      limitations were small sample size and inclusion of only one site. Additionally,
      participants were not queried about their group assignments. CONCLUSIONS:
      Pulsatile lavage enhanced stage III and IV pelvic pressure ulcer healing rates in
      people with SCI relative to standard pressure ulcer treatment alone.

PMID- 21949433
TI  - A vision for society: physical therapy as partners in the national health agenda.

PMID- 21949434
TI  - Organisational characteristics associated with the use of daily interruption of
      sedation in US hospitals: a national study.
AB  - OBJECTIVE: Daily interruption of sedation (DIS) has multiple proven benefits, but
      implementation is erratic. Past research on sedative interruption utilisation
      focused on individual clinicians, ignoring the role of organisations in shaping
      practice. The authors test the hypothesis that specific hospital organisational
      characteristics are associated with routine use of DIS. DESIGN AND SETTING:
      National, mailed survey to a stratified random sample of US hospitals in 2009.
      Respondents were the lead infection control professionals at each institution.
      METHODS: Survey items enquired about DIS use, institutional structure, and
      organisational culture. Multivariable analysis was used to evaluate the
      independent association of these factors with DIS use. RESULTS: A total of 386
      hospitals formed our final analytic sample; the response rate was 69.4%.
      Hospitals ranged in size from 25 to 1359 beds. 26% of hospitals were associated
      with a medical school. Almost 80% reported regular use of DIS for ventilated
      patients. While 75.4% of hospitals reported having leadership focus on safety
      culture, only 42.7% reported that their staff were receptive to changes in
      practice. In a multivariable logistic regression model, structural
      characteristics such as size and academic affiliation were not associated with
      use of DIS. However, leadership emphasis on safety culture (p=0.04), staff
      receptivity to change (p=0.02) and involvement in an infection prevention
      collaborative (p=0.04) were significantly associated with regular DIS use.
      CONCLUSIONS: Several elements of hospital organisational culture were associated
      with regular use of DIS in US hospitals. These findings emphasise the importance
      of combining specific administrative approaches with strategies to encourage
      receptivity to change among bedside clinicians in order to successfully implement
      complex evidence-based practices in the intensive care setting.

PMID- 21949435
TI  - Striving to achieve best practice in heart failure disease management.

PMID- 21949436
TI  - Uncovering the blind spot of patient satisfaction: an international survey.
AB  - BACKGROUND: To achieve a high level of patient satisfaction, providers need to
      identify and address patients' expectations. However, providers' beliefs and
      attitudes regarding expectations, as well as how to manage them, are not well
      understood. METHODS: The authors developed a survey to assess clinicians'
      awareness, attitudes, competence and performance with respect to patient
      expectations. The authors surveyed clinicians in four academic hospitals located
      in Denmark, Israel, the UK and the USA. RESULTS: The authors collected 1004
      questionnaires (79.9% response rate) from four hospitals in four countries
      spanning three continents. Overall, 88.8% of respondents stated that clinician
      awareness regarding patient expectations was moderate to low, with significant
      differences between countries (p<0.001). Although 89.4% of clinicians believed it
      was important to ask patients about expectations, only 16.1% reported actually
      asking (p<0.0001). Nurses were more likely than physicians to ask patients about
      expectations (20.1% vs 11.5%, p<0.001). Only 19.6% of respondents felt they had
      adequate training to handle patients' expectations. In multivariate analyses,
      clinicians with greater awareness and adequate training were more likely to ask
      patients about their expectations. CONCLUSION: While clinicians think it is
      important to ask patients about their expectations, they often fail to do so and
      consequently may not respond adequately. These results identify a 'blind spot' in
      clinicians' approach when attempting to address patient expectations and improve
      patient satisfaction, suggesting that healthcare organisations should take a more
      active role in increasing clinicians' awareness and initiating structured
      training programmes to cope with patient expectations.

PMID- 21949437
TI  - How event reporting by US hospitals has changed from 2005 to 2009.
AB  - CONTEXT: Information is needed on the performance of hospitals' adverse-event
      reporting systems and the effects of national patient-safety initiatives,
      including the Patient Safety and Quality Improvement Act (PSQIA) of 2005. Results
      are presented of a 2009 survey of a sample of non-federal US hospitals and
      changes between 2005 and 2009 are examined. METHODS: The Adverse Event Reporting
      System survey was fielded in 2005 and 2009 using a mixed-mode design with
      stratified random samples of non-federal US hospitals; risk managers were
      respondents. Response rates were 81% in 2005 and 79% in 2009. RESULTS: Virtually
      all hospitals reported they had centralised adverse-event-reporting systems.
      However, scores on four performance indexes suggested that hospitals have not
      effectively implemented key components of reporting systems. Average index scores
      improved somewhat between 2005 and 2009 for supportive environment (0.7 increase;
      p<0.05) and types of staff reporting (0.08 increase; p<0.001). Average scores did
      not change for timely distribution of event reports or discussion with key
      departments and committees. Some within-hospital inconsistencies in responses
      between 2005 and 2009 were found. These self-reported responses may be optimistic
      assessments of hospital performance. CONCLUSIONS: The 2009 survey confirmed
      improvement needs identified by the 2005 survey for hospitals' event reporting
      processes, while finding signs of progress. Optimising the use of surveys to
      assess the effects of national patient-safety initiatives such as PSQIA will
      require decreasing within-hospital variations in reporting rates.

PMID- 21949438
TI  - Factors associated with disclosure of medical errors by housestaff.
AB  - PURPOSE: Attributes of the organisational culture of residency training
      programmes may impact patient safety. Training environments are complex, composed
      of clinical teams, residency programmes, and clinical units. We examined the
      relationship between residents' perceptions of their training environment and
      disclosure of or apology for their worst error. METHOD: Anonymous, self
      administered surveys were distributed to Medicine and Surgery residents at Boston
      Medical Center in 2005. Surveys asked residents to describe their worst medical
      error, and to answer selected questions from validated surveys measuring elements
      of working environments that promote learning from error. Subscales measured the
      microenvironments of the clinical team, residency programme, and clinical unit.
      Univariate and bivariate statistical analyses examined relationships between
      trainee characteristics, their perceived learning environment(s), and their
      responses to the error. RESULTS: Out of 109 surveys distributed to residents, 99
      surveys were returned (91% overall response rate), two incomplete surveys were
      excluded, leaving 97: 61% internal medicine, 39% surgery, 59% male residents.
      While 31% reported apologising for the situation associated with the error, only
      17% reported disclosing the error to patients and/or family. More male residents
      disclosed the error than female residents (p=0.04). Surgery residents scored
      higher on the subscales of safety culture pertaining to the residency programme
      (p=0.02) and managerial commitment to safety (p=0.05). Our Medical Culture
      Summary score was positively associated with disclosure (p=0.04) and apology
      (p=0.05). CONCLUSION: Factors in the learning environments of residents are
      associated with responses to medical errors. Organisational safety culture can be
      measured, and used to evaluate environmental attributes of clinical training that
      are associated with disclosure of, and apology for, medical error.

PMID- 21949439
TI  - Using health status to measure NHS performance: another step into the dark for
      the health reform in England.
AB  - The National Health Service in England is moving away from targets based on
      processes of care and focusing on patient outcomes. This vision is
      operationalised in the recently published NHS Outcomes Framework, which includes
      the generalised use of Patient Reported Outcomes (health status and quality of
      life) as measures of population health at the provider level. This is the first
      time that such a bold initiative is attempted in the UK and it is not without
      risks. In this article we elaborate on our experience on the use of Patient
      Reported Outcomes and identify challenges and likely implications of this
      approach and suggest less disruptive alternatives.

PMID- 21949440
TI  - Using health status to measure NHS performance: casting light in dark places.

PMID- 21949442
TI  - Falls in older people on hemodialysis.

PMID- 21949441
TI  - Implementing a systems-oriented morbidity and mortality conference in remote
      rural Nepal for quality improvement.
AB  - PROBLEM: In hospitals in rural, resource-limited settings, there is an acute need
      for simple, practical strategies to improve healthcare quality. SETTING: A
      district hospital in remote western Nepal. KEY MEASURES FOR IMPROVEMENT: To
      provide a mechanism for systems-level reflection so that staff can identify
      targets for quality improvement in healthcare delivery. Strategies for change To
      develop a morbidity and mortality conference (M&M) quality improvement initiative
      that aims to facilitate structured analysis of patient care and identify barriers
      to providing quality care, which can subsequently be improved. DESIGN: The
      authors designed an M&M involving clinical and non-clinical staff in conducting
      root-cause analyses of healthcare delivery at their hospital. Weekly conferences
      focus on seven domains of causal analysis: operations, supply chain, equipment,
      personnel, outreach, societal, and structural. Each conference focuses on
      assessing the care provided, and identifying ways in which services can be
      improved in the future. EFFECTS OF CHANGE: Staff reception of the M&Ms was
      positive. In these M&Ms, staff identified problem areas in healthcare delivery
      and steps for improvement. Subsequently, changes were made in hospital workflow,
      supply procurement, and on-site training. LESSONS LEARNT: While widely practiced
      throughout the world, M&Ms typically do not involve both clinical and non
      clinical staff members and do not take a systems-level approach. The authors'
      experience suggests that the adapted M&M conference is a simple, feasible tool
      for quality improvement in resource-limited settings. Senior managerial
      commitment is crucial to ensure successful implementation of M&Ms, given the
      challenging logistics of implementing these programmes in resource-limited health
      facilities.

PMID- 21949443
TI  - Analytical Derivation of Moment Equations in Stochastic Chemical Kinetics.
AB  - The master probability equation captures the dynamic behavior of a variety of
      stochastic phenomena that can be modeled as Markov processes. Analytical
      solutions to the master equation are hard to come by though because they require
      the enumeration of all possible states and the determination of the transition
      probabilities between any two states. These two tasks quickly become intractable
      for all but the simplest of systems. Instead of determining how the probability
      distribution changes in time, we can express the master probability distribution
      as a function of its moments, and, we can then write transient equations for the
      probability distribution moments. In 1949, Moyal defined the derivative, or jump,
      moments of the master probability distribution. These are measures of the rate of
      change in the probability distribution moment values, i.e. what the impact is of
      any given transition between states on the moment values. In this paper we
      present a general scheme for deriving analytical moment equations for any N
      dimensional Markov process as a function of the jump moments. Importantly, we
      propose a scheme to derive analytical expressions for the jump moments for any N
      dimensional Markov process. To better illustrate the concepts, we focus on
      stochastic chemical kinetics models for which we derive analytical relations for
      jump moments of arbitrary order. Chemical kinetics models are widely used to
      capture the dynamic behavior of biological systems. The elements in the jump
      moment expressions are a function of the stoichiometric matrix and the reaction
      propensities, i.e the probabilistic reaction rates. We use two toy examples, a
      linear and a non-linear set of reactions, to demonstrate the applicability and
      limitations of the scheme. Finally, we provide an estimate on the minimum number
      of moments necessary to obtain statistical significant data that would uniquely
      determine the dynamics of the underlying stochastic chemical kinetic system. The
      first two moments only provide limited information, especially when complex, non
      linear dynamics are involved.

PMID- 21949444
TI  - Academic Giftedness and Alcohol Use in Early Adolescence.
AB  - Adolescence is a period of development particularly vulnerable to the effects of
      alcohol use, with recent studies underscoring alcohol's effects on adolescent
      brain development. Despite the alarming rates and consequences of adolescent
      alcohol use, gifted adolescents are often overlooked as being at risk for early
      alcohol use. Although gifted adolescents may possess protective factors that
      likely inhibit the use of alcohol, some gifted youth may be vulnerable to
      initiating alcohol use during adolescence as experimenting with alcohol may be
      one way gifted youth choose to compensate for the social price (whether real or
      perceived) of their academic talents. To address the dearth of research on
      alcohol use among gifted adolescents the current study (a) examined the extent to
      which gifted adolescents use alcohol relative to their nongifted peers and (b)
      examined the adjustment profile of gifted adolescents who had tried alcohol
      relative to nongifted adolescents who tried alcohol as well as gifted and
      nongifted abstainers. More than 300 students in seventh grade (42.5% gifted)
      participated in the present study. Results indicated gifted students have, in
      fact, tried alcohol at rates that do not differ from nongifted students. Although
      trying alcohol was generally associated with negative adjustment, giftedness
      served as a moderating factor such that gifted students who had tried alcohol
      were less at risk than their nongifted peers. However, evidence also suggests
      that gifted adolescents who tried alcohol may be a part of a peer context that
      promotes substance use, which may place these youth at risk for adjustment
      difficulties in the future.

PMID- 21949445
TI  - SYNTHESIS OF TRIFLUOROMETHYL-IMINES BY SOLID ACID/SUPERACID CATALYZED MICROWAVE
      ASSISTED APPROACH.
AB  - A new solid acid/superacid catalyzed microwave assisted synthesis of
      trifluoromethyl-imines is described. Various alpha,alpha,alpha
      trifluoromethylketones react readily with primary amines to produce the
      corresponding imines. Two different strategies have been employed; one is the
      application of microwave irradiation coupled with solvent-free solid acid
      catalysis. The other method, for highly deactivated substrates includes the use
      of a pressure vessel at 175  degrees C temperature, with solid superacid
      catalysis. Using the solid acid K-10 montmorillonite or the superacidic
      perfluorinated resinsulfonic acid Nafion-H, a wide variety of trifluoromethylated
      imines have been synthesized using the above methods. The products have been
      isolated in good to excellent yields and high selectivities. This new
      environmentally friendly synthetic methodology provides significantly higher
      yields than traditional methods during relatively short reaction times for the
      preparation of the target compounds.

PMID- 21949446
TI  - Importing the Poor: Welfare Magnetism and Cross-Border Welfare Migration.
AB  - I test for welfare-induced migration by comparing AFDC participation in border
      counties to interior counties in the same state. If migration costs are lower for
      border county residents, border counties on the high-benefit side of a state
      border should have higher welfare participation relative to the state's interior
      counties. Border counties on the low-benefit side should have lower welfare
      participation relative to the state's interior counties. The results obtained
      using county-level data from 1970-90 indicate that having a neighbor with
      benefits that are $100 lower increases AFDC expenditures in border counties by
      4.0-6.8 percent relative to interior counties.

PMID- 21949447
TI  - Evolutionary Debunking Arguments.
AB  - Evolutionary debunking arguments (EDAs) are arguments that appeal to the
      evolutionary origins of evaluative beliefs to undermine their justification. This
      paper aims to clarify the premises and presuppositions of EDAs-a form of argument
      that is increasingly put to use in normative ethics. I argue that such arguments
      face serious obstacles. It is often overlooked, for example, that they presuppose
      the truth of metaethical objectivism. More importantly, even if objectivism is
      assumed, the use of EDAs in normative ethics is incompatible with a parallel and
      more sweeping global evolutionary debunking argument that has been discussed in
      recent metaethics. After examining several ways of responding to this global
      debunking argument, I end by arguing that even if we could resist it, this would
      still not rehabilitate the current targeted use of EDAs in normative ethics given
      that, if EDAs work at all, they will in any case lead to a truly radical revision
      of our evaluative outlook.

PMID- 21949448
TI  - Partnership Instability, School Readiness, and Gender Disparities.
AB  - Trends in family formation during the past several decades have increased
      children's exposure to mothers' partnership instability, defined as an entrance
      into or exit from a coresidential union or a dating partnership. Instability, in
      turn, is associated with negative outcomes for children and adolescents. This
      study uses data from the Fragile Families and Child Wellbeing Study to examine
      associations between mothers' partnership instability and children's school
      readiness, differences between coresidential and dating transitions, and the
      moderating role of child gender. Mothers' partnership transitions are negatively
      associated with children's verbal ability and positively associated with boys'
      behavioral problems at age five. In general, coresidential and dating transitions
      have similar effects on school readiness. The findings have important
      implications for our understanding of the growing gender gap in educational
      attainment.

PMID- 21949449
TI  - Welfare-Induced Migration at State Borders: New Evidence from Micro-Data.
AB  - This paper extends and synthesizes the various approaches used in the recent
      welfare migration literature to both offer the most comprehensive set of tests to
      date for welfare migration and to also determine the relative importance of short
      distance moves in welfare migration flows. The current study follows on the
      finding of McKinnish (2005) of welfare migration effects obtained by comparing
      welfare participation at state borders to state interiors. This identification
      strategy is extended to micro-data from the 1980 and 1990 Decennial Censuses and
      combined with the demographic comparisons used elsewhere in the welfare migration
      literature. The signs and patterns of the estimates are consistent with the
      presence of welfare migration effects, and the magnitudes of the estimates are
      consistent with the importance of short-distance moves in welfare-induced
      migration flows, but most of the estimates are not statistically significant.

PMID- 21949450
TI  - A Vaccine Against Ignorance?

PMID- 21949451
TI  - An Overview of Biodegradation of LNAPLs in Coastal (Semi)-arid Environment.
AB  - Contamination of soil and water due to the release of light non-aqueous phase
      liquids (LNAPLs) is a ubiquitous problem. The problem is more severe in arid and
      semi-arid coastal regions where most of the petroleum production and related
      refinery industries are located. Biological treatment of these organic
      contaminated resources is receiving increasing interests and where applicable,
      can serve as a cost-effective remediation alternative. The success of
      bioremediation greatly depends on the prevailing environmental variables, and
      their remediation favoring customization requires a sound understanding of their
      integrated behavior on fate and transport of LNAPLs under site-specific
      conditions. The arid and semi-arid coastal sites are characterized by specific
      environmental extremes; primarily, varying low and high temperatures, high
      salinity, water table dynamics, and fluctuating soil moisture content. An
      understanding of the behavior of these environmental variables on biological
      interactions with LNAPLs would be helpful in customizing the bioremediation for
      restoring problematic sites in these regions. Therefore, this paper reviews the
      microbial degradation of LNAPLs in soil-water, considering the influences of
      prevailing environmental parameters of arid and semi-arid coastal regions. First,
      the mechanism of biodegradation of LNAPLs is discussed briefly, followed by a
      summary of popular kinetic models used by researchers for describing the
      degradation rate of these hydrocarbons. Next, the impact of soil moisture
      content, water table dynamics, and soil-water temperature on the fate and
      transport of LNAPLs are discussed, including an overview of the studies conducted
      so far. Finally, based on the reviewed information, a general conclusion is
      presented with recommendations for future research subjects on optimizing the
      bioremediation technique in the field under the aforesaid environmental
      conditions. The present review will be useful to better understand the
      feasibility of bioremediation technology, in general, and its applicability for
      remediating LNAPLs polluted lands under aforesaid environments, in particular.

PMID- 21949452
TI  - Screening of Microorganisms for Biodegradation of Simazine Pollution (Obsolete
      Pesticide Azotop 50 WP).
AB  - The capability of environmental microorganisms to biodegrade simazine-an active
      substance of 2-chloro-s-triazine herbicides (pesticide waste since 2007)-was
      assessed. An enormous metabolic potential of microorganisms impels to explore the
      possibilities of using them as an alternative way for thermal and chemical
      methods of utilization. First, the biotope rich in microorganisms resistant to
      simazine was examined. Only the higher dose of simazine (100 mg/l) had an actual
      influence on quantity of bacteria and environmental fungi incubated on substrate
      with simazine. Most simazine-resistant bacteria populated activated sludge and
      biohumus (vermicompost); the biggest strain of resistant fungi was found in
      floral soil and risosphere soil of maize. Compost and biohumus were the sources
      of microorganisms which biodegraded simazine, though either of them was the
      dominant considering the quantity of simazine-resistant microorganisms. In both
      cases of periodic culture (microorganisms from biohumus and compost), nearly 100%
      of simazine (50 mg/l) was degraded (within 8 days). After the repeated enrichment
      culture with simazine, the rate of its degradation highly accelerated, and just
      after 24 h, the significant decrease of simazine (20% in compost and 80% in
      biohumus) was noted. Although a dozen attempts of isolating various strains
      responsible for biodegradation of simazine from compost and biohumus were
      performed, only the strain identified as Arthrobacter urefaciens (NC) was
      obtained, and it biodegraded simazine with almost 100% efficiency (within 4
      days).

PMID- 21949453
TI  - A comment to the paper by Waltman et al., Scientometrics, 87, 467-481, 2011.
AB  - In reaction to a previous critique (Opthof and Leydesdorff, J Informetr 4(3):423
      430, 2010), the Center for Science and Technology Studies (CWTS) in Leiden
      proposed to change their old "crown" indicator in citation analysis into a new
      one. Waltman (Scientometrics 87:467-481, 2011a) argue that this change does not
      affect rankings at various aggregated levels. However, CWTS data is not publicly
      available for testing and criticism. Therefore, we comment by using previously
      published data of Van Raan (Scientometrics 67(3):491-502, 2006) to address the
      pivotal issue of how the results of citation analysis correlate with the results
      of peer review. A quality parameter based on peer review was neither
      significantly correlated with the two parameters developed by the CWTS in the
      past citations per paper/mean journal citation score (CPP/JCSm) or CPP/FCSm
      (citations per paper/mean field citation score) nor with the more recently
      proposed h-index (Hirsch, Proc Natl Acad Sci USA 102(46):16569-16572, 2005).
      Given the high correlations between the old and new "crown" indicators, one can
      expect that the lack of correlation with the peer-review based quality indicator
      applies equally to the newly developed ones.

PMID- 21949454
TI  - On the correlation between bibliometric indicators and peer review: reply to
      Opthof and Leydesdorff.
AB  - Opthof and Leydesdorff (Scientometrics, 2011) reanalyze data reported by Van Raan
      (Scientometrics 67(3):491-502, 2006) and conclude that there is no significant
      correlation between on the one hand average citation scores measured using the
      CPP/FCSm indicator and on the other hand the quality judgment of peers. We point
      out that Opthof and Leydesdorff draw their conclusions based on a very limited
      amount of data. We also criticize the statistical methodology used by Opthof and
      Leydesdorff. Using a larger amount of data and a more appropriate statistical
      methodology, we do find a significant correlation between the CPP/FCSm indicator
      and peer judgment.

PMID- 21949455
TI  - The Level of Knowledge and Behavior of Adolescent Male and Female Students in
      Turkey on the Matter of Reproductive Health.
AB  - In this research, the objective is to determine the level of knowledge, the
      sources of information and the behavior of adolescent male and female students in
      Turkey on the matter of reproductive health. The sample is comprised of 600
      students randomly chosen from four different elementary schools. The survey form
      was used for data collection. In analyzing the data, we calculated averages and
      performed Chi-square tests. We determined that 82.3% of the students are aware of
      the changes in their own bodies, and 69.2% of them have knowledge about the place
      and the functions of their reproductive organs. We found established that 55.2%
      of the students have knowledge about puberty prior to this phase, and girls
      attain this knowledge mostly (78.2%) through their mothers, whereas boys (25.4%)
      attain it from the media. We found significant differences between boys and
      girls, including the following: the level of disturbance caused by puberty
      symptoms, the individuals informed about the symptoms, the feelings and the style
      of dress in puberty, and situations such as being happy or unhappy about the
      symptoms differ according to the sex of the student. These findings are
      statistically significant (p < 0.00). It is observed that the perception of
      puberty symptoms is different for boys and girls, and the girls are more open to
      communicate with their mothers, while the boys are more open to communicate with
      their friends.

PMID- 21949457
TI  - Gambling Behaviors Among Oxford House Residents: A Preliminary Investigation.
AB  - The present study investigated the prevalence of gambling behaviors among 71
      individuals recovering from substance-dependent disorders and living in self-run
      recovery homes (Oxford Houses). Residents were given the South Oaks Gambling
      Screen to assess gambling behaviors and pathological gambling, and 19.7% of the
      sample was identified as having probable pathological gambling. These residents
      reported proportionately more involvement in a variety of gambling behaviors than
      other residents. Engagement in various gambling activities was consistent with
      previous investigations and suggested that self-run recovery homes such as Oxford
      Houses might be suitable referral sources for recovering persons who have
      comorbid gambling problems.

PMID- 21949458
TI  - Organizational  characteristics  that  foster  early  adoption  of  cultural  and
      linguistic competence  in  outpatient  substance  abuse  treatment  in  the 
      United  States.
AB  - Recent years have seen an increased interest in developing culturally and
      linguistically responsive systems of care in substance abuse treatment in the
      United States. This study examines the extent to which external and internal
      organizational pressures contributed to the degree of adoption of culturally and
      linguistically responsive practices in the nation's outpatient substance abuse
      treatment system early in the period of development of this system of care.
      Findings show that a higher degree of adoption of culturally competent practices
      was most likely in treatment programs with high dependence on external funding
      and regulation. Internally, programs with a larger number of professionals were
      associated with the lowest degree of adoption, while managers' cultural
      sensitivity contributed significantly to a high degree of adoption of these
      responsive practices. Considering the passage of recent legislation enforcing the
      use of cultural and linguistic competence in health care, implications of these
      baseline findings on early adoption patterns are discussed for future research
      and health care policy evaluation.

PMID- 21949459
TI  - Big Data: Large-Scale Historical Infrastructure from the Minnesota Population
      Center.
AB  - The Minnesota Population Center (MPC) provides aggregate data and microdata that
      have been integrated and harmonized to maximize crosstemporal and cross-spatial
      comparability. All MPC data products are distributed free of charge through an
      interactive Web interface that enables users to limit the data and metadata being
      analyzed to samples and variables of interest to their research. In this article,
      the authors describe the integrated databases available from the MPC, report on
      recent additions and enhancements to these data sets, and summarize new online
      tools and resources that help users to analyze the data over time. They conclude
      with a description of the MPC's newest and largest infrastructure project to
      date: a global population and environment data network.

PMID- 21949456
TI  - Structure and function of the skeletal muscle extracellular matrix.
AB  - The skeletal muscle extracellular matrix (ECM) plays an important role in muscle
      fiber force transmission, maintenance, and repair. In both injured and diseased
      states, ECM adapts dramatically, a property that has clinical manifestations and
      alters muscle function. Here we review the structure, composition, and mechanical
      properties of skeletal muscle ECM; describe the cells that contribute to the
      maintenance of the ECM; and, finally, overview changes that occur with pathology.
      New scanning electron micrographs of ECM structure are also presented with
      hypotheses about ECM structure-function relationships. Detailed structure
      function relationships of the ECM have yet to be defined and, as a result, we
      propose areas for future study.

PMID- 21949460
TI  - Power and sample size requirements for non-inferiority in studies comparing two
      matched proportions where the events are correlated.
AB  - Consider clustered matched-pair studies for non-inferiority where clusters are
      independent but units in a cluster are correlated. An inexpensive new procedure
      and the expensive standard one are applied to each unit and outcomes are binary
      responses. Appropriate statistics testing non-inferiority of a new procedure have
      been developed recently by several investigators. In this note, we investigate
      power and sample size requirement of the clustered matched pair study for non
      inferiority. Power of a test is related primarily to the number of clusters. The
      effect of a cluster size on power is secondary. The efficiency of a clustered
      matched-pair design is inversely related to the intra-class correlation
      coefficient within a cluster. We present an explicit formula for obtaining the
      number of clusters for given a cluster size and the cluster size for a given
      number of clusters for a specific power. We also provide alternative sample size
      calculations when available information regarding parameters are limited. The
      formulae can be useful in designing a clustered matched-pair study for non
      inferiority. An example for determining sample size to establish non-inferiority
      for a clustered matched-pair study is illustrated.

PMID- 21949461
TI  - Working With What We've Got: Perceptions of Barriers and Supports Among Small
      Metropolitan Same-Sex Adopting Couples.
AB  - In seeking to adopt, lesbians and gay men may confront various barriers and
      obstacles. Ideally they have access to a variety of support resources that can
      help to buffer the negative effects of these barriers. However, lesbians and gay
      men living in small-metropolitan communities may have limited access to support
      resources. The current qualitative study examined the perceptions of 37 same-sex
      couples who were pursuing adoption while living outside of large metropolitan
      cities, with attention to the barriers these couples encountered during the
      adoption process, and the resources they drew upon to cope with such challenges.
      Findings indicated that same sex couples living in small-metropolitan areas
      confronted several major barriers in the adoption process, such as a lack of
      geographically accessible gay-friendly adoption agencies. Despite limited access
      to support, participants showed evidence of notable resourcefulness. For example,
      participants with limited access to formal support groups sought out informal
      supports instead.

PMID- 21949463
TI  - Medical competence, anatomy and the polity in seventeenth-century Rome.
AB  - At the centre of this article are two physicians active in Rome between 1600 and
      1630 who combined medical practice with broader involvement in the dynamic
      cultural, economic and political scene of the centre of the Catholic world. The
      city's distinctive and very influential social landscape magnified issues of
      career-building and allows us to recapture physicians' different strategies of
      self-fashioning at a time of major social and religious reorganization. At one
      level, reconstructing Johannes Faber and Giulio Mancini's medical education,
      arrival in Rome and overlapping but different career trajectories contributes to
      research on physicians' identity in early modern Italian states. Most remarkable
      are their access to different segments of Roman society, including a dynamic art
      market, and their diplomatic and political role, claimed as well as real. But
      following these physicians from hospitals to courts, including that of the Pope,
      and from tribunals to the university and analysing the wide range of their
      writing - from medico-legal consilia to political essays and reports of
      anatomical investigations - also enriches our view of medical practice, which
      included, but went beyond, the bedside. Furthermore, their activities demand that
      we reassess the complex place of anatomical investigations in a courtly society,
      and start recovering the fundamental role played by hospitals - those
      quintessential Catholic institutions - as sites of routine dissections for both
      medical teaching and research. (pp. 551-567).

PMID- 21949462
TI  - Emerging of Stochastic Dynamical Equalities and Steady State Thermodynamics from
      Darwinian Dynamics.
AB  - The evolutionary dynamics first conceived by Darwin and Wallace, referring to as
      Darwinian dynamics in the present paper, has been found to be universally valid
      in biology. The statistical mechanics and thermodynamics, while enormous
      successful in physics, have been in an awkward situation of wanting a consistent
      dynamical understanding. Here we present from a formal point of view an
      exploration of the connection between thermodynamics and Darwinian dynamics and a
      few related topics. We first show that the stochasticity in Darwinian dynamics
      implies the existence temperature, hence the canonical distribution of Boltzmann
      Gibbs type. In term of relative entropy the Second Law of thermodynamics is
      dynamically demonstrated without detailed balance condition, and is valid
      regardless of size of the system. In particular, the dynamical component
      responsible for breaking detailed balance condition does not contribute to the
      change of the relative entropy. Two types of stochastic dynamical equalities of
      current interest are explicitly discussed in the present approach: One is based
      on Feynman-Kac formula and another is a generalization of Einstein relation. Both
      are directly accessible to experimental tests. Our demonstration indicates that
      Darwinian dynamics represents logically a simple and straightforward starting
      point for statistical mechanics and thermodynamics and is complementary to and
      consistent with conservative dynamics that dominates the physical sciences.
      Present exploration suggests the existence of a unified stochastic dynamical
      framework both near and far from equilibrium.

PMID- 21949464
TI  - Age before beauty? Relationships between fertilization success and age-dependent
      ornaments in barn swallows.
AB  - When males become more ornamented and reproduce more successfully as they grow
      older, phenotypic correlations between ornament exaggeration and reproductive
      success can be confounded with age effects in cross-sectional studies, and thus
      say relatively little about sexual selection on these traits. This is exemplified
      here in a correlative study of male fertilization success in a large colony of
      American barn swallows (Hirundo rustica erythrogaster). Previous studies of this
      species have indicated that two sexually dimorphic traits, tail length and
      ventral plumage coloration, are positively correlated with male fertilization
      success, and a mechanism of sexual selection by female choice has been invoked.
      However, these studies did not control for potential age-related variation in
      trait expression. Here, we show that male fertilization success was positively
      correlated with male tail length but not with plumage coloration. We also show
      that 1-year-old males had shorter tails and lower fertilization success than
      older males. This age effect accounted for much of the covariance between tail
      length and fertilization success. Still, there was a positive relationship
      between tail length and fertilization success among older males. But as this
      group consisted of males from different age classes, an age effect may be hidden
      in this relationship as well. Our data also revealed a longitudinal increase in
      both tail length and fertilization success for individual males. We argue that
      age-dependent ornament expression and reproductive performance in males
      complicate inferences about female preferences and sexual selection.

PMID- 21949465
TI  - OPE, charm-quark mass, and decay constants of D and Ds mesons from QCD sum rules.
AB  - We present a sum-rule extraction of the decay constants of the charmed mesons D
      and Ds from the two-point correlator of pseudoscalar currents. First, we compare
      the perturbative expansion for the correlator and the decay constant performed in
      terms of the pole and the running MS- masses of the charm quark. The perturbative
      expansion in terms of the pole mass shows no signs of convergence whereas
      reorganizing this very expansion in terms of the MS- mass leads to a distinct
      hierarchy of the perturbative expansion. Furthermore, the decay constants
      extracted from the pole-mass correlator turn out to be considerably smaller than
      those obtained by means of the MS--mass correlator. Second, making use of the OPE
      in terms of the MS- mass, we determine the decay constants of both D and Ds
      mesons with an emphasis on the uncertainties in these quantities related both to
      the input QCD parameters and to the limited accuracy of the method of sum rules.

PMID- 21949466
TI  - The Servant Leadership Survey: Development and Validation of a Multidimensional
      Measure.
AB  - PURPOSE: The purpose of this paper is to describe the development and validation
      of a multi-dimensional instrument to measure servant leadership. 
      DESIGN/METHODOLOGY/APPROACH: Based on an extensive literature review and expert
      judgment, 99 items were formulated. In three steps, using eight samples totaling
      1571 persons from The Netherlands and the UK with a diverse occupational
      background, a combined exploratory and confirmatory factor analysis approach was
      used. This was followed by an analysis of the criterion-related validity. 
      FINDINGS: The final result is an eight-dimensional measure of 30 items: the eight
      dimensions being: standing back, forgiveness, courage, empowerment,
      accountability, authenticity, humility, and stewardship. The internal consistency
      of the subscales is good. The results show that the Servant Leadership Survey
      (SLS) has convergent validity with other leadership measures, and also adds
      unique elements to the leadership field. Evidence for criterion-related validity
      came from studies relating the eight dimensions to well-being and performance. 
      IMPLICATIONS: With this survey, a valid and reliable instrument to measure the
      essential elements of servant leadership has been introduced.  ORIGINALITY/VALUE:
      The SLS is the first measure where the underlying factor structure was developed
      and confirmed across several field studies in two countries. It can be used in
      future studies to test the underlying premises of servant leadership theory. The
      SLS provides a clear picture of the key servant leadership qualities and shows
      where improvements can be made on the individual and organizational level; as
      such, it may also offer a valuable starting point for training and leadership
      development.

PMID- 21949467
TI  - The Vernacular Landscape of Assisted Living.
AB  - This article is an exploration into the vernacular landscape of Assisted Living
      (AL), a conceptual idea borrowed from cultural geographer J.B. Jackson, which
      distinguishes formalized, planned space from those spaces which are unintended
      and often created spontaneously--vernacular. Based upon three large-scale, multi
      year ethnographic studies in Maryland, we consider some of the ways people who
      live in AL relate to and respond to the built environment, at times subverting
      the intended purpose of design to make it their own. The conflict that often
      ensues over both planned and vernacular public and private space, we propose is
      ultimately the product of living within an environment that is both someone's
      home as well as a place of business, whose job it is to keep people safe. Within
      this physical context of vernacular private and public spaces, this article
      enriches understandings about the way autonomy and privacy expresses itself.

PMID- 21949468
TI  - New aspects of the elastic net algorithm for cluster analysis.
AB  - The elastic net algorithm formulated by Durbin-Willshaw as a heuristic method and
      initially applied to solve the traveling salesman problem can be used as a tool
      for data clustering in n-dimensional space. With the help of statistical
      mechanics, it is formulated as a deterministic annealing method, where a chain
      with a fixed number of nodes interacts at different temperatures with the data
      cloud. From a given temperature on the nodes are found to be the optimal
      centroids of fuzzy clusters, if the number of nodes is much smaller than the
      number of data points. We show in this contribution that for this temperature,
      the centroids of hard clusters, defined by the nearest neighbor clusters of every
      node, are in the same position as the optimal centroids of the fuzzy clusters.
      The same is true for the standard deviations. This result can be used as a
      stopping criterion for the annealing process. The stopping temperature and the
      number and sizes of the hard clusters depend on the number of nodes in the chain.
      Test was made with homogeneous and nonhomogeneous artificial clusters in two
      dimensions. A medical application is given to localize tumors and their size in
      images of a combined measurement of X-ray computed tomography and positron
      emission tomography.

PMID- 21949469
TI  - The effect of moisture absorption on the physical properties of polyurethane
      shape memory polymer foams.
AB  - The effect of moisture absorption on the glass transition temperature (T(g)) and
      stress/strain behavior of network polyurethane shape memory polymer (SMP) foams
      has been investigated. With our ultimate goal of engineering polyurethane SMP
      foams for use in blood contacting environments, we have investigated the effects
      of moisture exposure on the physical properties of polyurethane foams. To our
      best knowledge, this study is the first to investigate the effects of moisture
      absorption at varying humidity levels (non-immersion and immersion) on the
      physical properties of polyurethane SMP foams. The SMP foams were exposed to
      differing humidity levels for varying lengths of time, and they exhibited a
      maximum water uptake of 8.0% (by mass) after exposure to 100% relative humidity
      for 96 h. Differential scanning calorimetry results demonstrated that water
      absorption significantly decreased the T(g) of the foam, with a maximum water
      uptake shifting the T(g) from 67  degrees C to 5  degrees C. Samples that were
      immersed in water for 96 h and immediately subjected to tensile testing exhibited
      100% increases in failure strains and 500% decreases in failure stresses;
      however, in all cases of time and humidity exposure, the plasticization effect
      was reversible upon placing moisture-saturated samples in 40% humidity
      environments for 24 h.

PMID- 21949471
TI  - Interactions Between MAOA Genotype and Receipt of Public Assistance: Predicting
      Change in Depressive Symptoms and Body Mass Index.
AB  - Response to stress is determined in part by genetically-influenced regulation of
      the monoamine system. We examined the interaction of a stressor (receipt of
      public assistance) and a gene regulating the monoamine system (MAOA) in the
      prediction of change in adolescent depressive symptoms and body mass index (BMI).
      Participants were drawn from the National Longitudinal Study on Adolescent Health
      (AddHealth) genetically-informative subsample. We focused on males due to the
      fact that males only have one MAOA allele. Growth curve analyses were conducted
      to assess the association between public assistance, MAOA allele, and their
      interaction and the intercept and slope of depressive symptoms and BMI. The
      results indicated that among males, MAOA allele type interacted with receipt of
      public assistance in the prediction of rate of change in both depressive symptoms
      and BMI from early adolescence through early adulthood. Males with the short MAOA
      allele whose families received public assistance tended to experience increased
      growth in depressive symptoms and BMI. Implications of the findings for
      understanding the relations among stress, physiology, and development are
      discussed.

PMID- 21949470
TI  - Prostate size correlates with fasting blood glucose in non-diabetic benign
      prostatic hyperplasia patients with normal testosterone levels.
AB  - We evaluated the correlations between BMI, fasting glucose, insulin, testosterone
      level, insulin resistance, and prostate size in non-diabetic benign prostatic
      hyperplasia (BPH) patients with normal testosterone levels. Data from 212 non
      diabetic BPH patients with normal testosterone levels, who underwent
      transurethral resection of the prostate (TURP) due to medical treatment failure,
      were evaluated retrospectively. Patients with prostate specific antigen (PSA)
      levels of >= 3 ng/mL underwent multicore transrectal prostate biopsy before TURP
      to rule out prostate cancer. Patients with diabetes mellitus (DM) or serum
      testosterone levels of < 3.50 ng/mL were excluded from analysis. Correlations
      between clinical and laboratory parameters were determined. Prostate size
      correlated positively with age (r = 0.227, P < 0.001), PSA (r = 0.510, P <
      0.001), and fasting glucose level (r = 0.186, P = 0.007), but not with BMI,
      testosterone, insulin level, or insulin resistance (each P > 0.05). Testosterone
      level inversely correlated with BMI (r = -0.327, P < 0.001), insulin level (r = 
      0.207, P = 0.003), and insulin resistance (r = -0.221, P = 0.001), but not with
      age, prostate size, PSA, or fasting glucose level (each P > 0.05). Upon multiple
      adjusted linear regression analysis, prostate size correlated with elevated PSA
      (P < 0.001) and increased fasting glucose levels (P = 0.023). In non-DM BPH
      patients with normal testosterone levels, fasting glucose level is an independent
      risk factor for prostate hyperplasia.

PMID- 21949472
TI  - Examination of a Process Model of Adolescent Smoking Self-Change Efforts in
      Relation to Gender.
AB  - Little information describes how adolescents change their smoking behavior. This
      study investigated the role of gender in the relationship of motivation and
      cognitive variables with adolescent smoking self-change efforts. Self-report and
      semi-structured interview data from a prospective study of smoking self-change
      efforts were examined among 98 adolescent smokers ages 14-18 (55% female). Social
      disapproval motives and short-term consequence reasons for quitting, quit self
      efficacy and intentions to quit were modeled in relation to prospective self-quit
      attempts assessed at a 6-month follow-up, separately by gender. Hypothesized
      mediating relationships were not supported although gender differences were
      noted. Social influence motives related to intention to quit and prospective self
      quit attempts among girls. For boys, intention to quit predicted making a self
      quit attempt. Findings emphasize the importance of examining adolescent models
      separately by gender and contribute to understanding of mechanisms involved in
      adolescent smoking change efforts.

PMID- 21949473
TI  - PREPARATIVE ISOLATION AND PURIFICATION OF FIVE FLAVONOIDS FROM POGOSTEMON CABLIN
      BENTH BY HIGH-SPEED COUNTERCURRENT CHROMATOGRAPHY AND PREPARATIVE HIGH
      PERFORMANCE LIQUID CHROMATOGRAPHY.
AB  - High-speed countercurrent chromatography (HSCCC) and preparative high-performance
      liquid chromatography (prep-HPLC) were successively used for the separation of
      pogostone and four flavonoids from Pogostemon cablin (Blanco) Benth. An efficient
      HSCCC separation was achieved on a two-phase solvent system composed of n-hexane
      ethyl acetate-methanol-water (11:5:11:5, v/v/v/v). Three well-separated peaks
      were obtained in the HSCCC chromatogram. The first and the second fractions each
      contained two flavonoids which were further separated by preparative HPLC.
      Consequently, the separation yielded 11.5 mg of 4', 5-Dihydroxy-3', 7
      dimethoxyflavanone at a purity of 99%, 20.3 mg of 5- Hydroxy-7, 3', 4'
      trimethoxyflavanone at a purity of 98%, 18 mg of 5, 4'-Dihydroxy-3, 7, 3'
      trimethoxyflavone at a purity of 96%, and 8 mg of 5-Hydroxy-3, 7, 4'
      tetramethoxyflvone at a purity of 98%. The third HSCCC fraction yielded 18.5 mg
      of pogostone at a purity of 95%. The chemical structures of these compounds were
      identified by ESI-MS(n), (1)H-NMR, and (13)C-NMR.

PMID- 21949475
TI  - Discussion of "Missing Data Methods in Longitudinal Studies: A Review" by Ibrahim
      and Molenberghs.

PMID- 21949474
TI  - Predictors and Effects of Training on an Online Health Education and Support
      System for Women with Breast Cancer.
AB  - Many breast cancer patients currently turn to Internet-based education and
      support to help them cope with their illness. This study explores the role of
      training in influencing how patients use a particular Interactive Cancer
      Communication System (ICCS) over time and also examines what pre-test
      characteristics predict which people are most likely to opt in or out of training
      in the first place. With use of pre-test survey and unobtrusive individual
      records of ICCS system use data (N = 216), nonparametric tests revealed that only
      having a later stage of cancer predicted whether or not patients participated in
      training. Results indicated that participating in training was a significant
      predictor of higher levels of using the CHESS system. In particular, the repeated
      measures analysis of covariance found the significant interaction as well as main
      effect of group (i.e., training vs. no training) and time (i.e., individual's
      CHESS usages at different times) in interactive and information CHESS services,
      suggesting that 1) the training group has a higher level of usage than the no
      training group, 2) both of the groups' usage decreased over time, and 3) these
      joint patterns hold over time. Practical guidelines for future ICCS campaign
      implementation are discussed.

PMID- 21949476
TI  - Comparison of LDA and SPRT on Clinical Dataset Classifications.
AB  - In this work, we investigate the well-known classification algorithm LDA as well
      as its close relative SPRT. SPRT affords many theoretical advantages over LDA. It
      allows specification of desired classification error rates alpha and beta and is
      expected to be faster in predicting the class label of a new instance. However,
      SPRT is not as widely used as LDA in the pattern recognition and machine learning
      community. For this reason, we investigate LDA, SPRT and a modified SPRT (MSPRT)
      empirically using clinical datasets from Parkinson's disease, colon cancer, and
      breast cancer. We assume the same normality assumption as LDA and propose
      variants of the two SPRT algorithms based on the order in which the components of
      an instance are sampled. Leave-one-out cross-validation is used to assess and
      compare the performance of the methods. The results indicate that two variants,
      SPRT-ordered and MSPRT-ordered, are superior to LDA in terms of prediction
      accuracy. Moreover, on average SPRT-ordered and MSPRT-ordered examine less
      components than LDA before arriving at a decision. These advantages imply that
      SPRT-ordered and MSPRT-ordered are the preferred algorithms over LDA when the
      normality assumption can be justified for a dataset.

PMID- 21949478
TI  - Changing Relationship Growth Belief: Intrapersonal and Interpersonal Consequences
      of Compassionate Goals.
AB  - The belief that difficulties can lead to growth in relationships, or growth
      belief, has consequences for relationships (e.g., Knee, 1998). But what predicts
      change in this belief? We hypothesized that compassionate goals to support others
      (Crocker & Canevello, 2008) predict increased growth belief through increased
      need satisfaction. In Study 1, 199 college freshmen reported their friendship
      growth belief and goals. In Study 2, 65 roommate pairs reported their roommate
      growth belief, goals, and need satisfaction. Across studies, compassionate goals
      predicted increased growth belief. In Study 2, goals predicted increased
      perceived mutual need satisfaction, which predicted increased growth belief.
      Additionally, partners' compassionate goals predicted actors' increased growth
      belief. Results suggest that growth beliefs are shaped by goals - own and
      others'.

PMID- 21949477
TI  - Mice with null mutation of Ceacam I develop nonalcoholic steatohepatitis.
AB  - Transgenic liver-specific inactivation of the carcinoembryonic antigen-related
      cell adhesion molecule (CEACAM1) impairs hepatic insulin clearance and causes
      hyperinsuline-mia, insulin resistance, elevation in hepatic and serum
      triglyceride levels, and visceral obesity. It also predisposes to nonalchoholic
      steatohepatitis (NASH) in response to a high-fat diet. To discern whether this
      phenotype reflects a physiological function of CEACAM1 rather than the effect of
      the dominant-negative transgene, we investigated whether Ceacam1 (gene encoding
      CEACAM1 protein) null mice with impaired insulin clearance also develop a NASH
      like phenotype on a prolonged high-fat diet. Three-month-old male null and wild
      type mice were fed a high-fat diet for 3 months and their NASH phenotype was
      examined. While high-fat feeding elevated hepatic triglyceride content in both
      strains of mice, it exacerbated macrosteatosis and caused NASH-characteristic
      fibrogenic changes and inflammatory responses more intensely in the null mouse.
      This demonstrates that CEACAM1-dependent insulin clearance pathways are linked
      with NASH pathogenesis.

PMID- 21949479
TI  - Emergency Dose Estimation Using Optically Stimulated Luminescence from Human
      Tooth Enamel.
AB  - Human teeth were studied for potential use as emergency Optically Stimulated
      Luminescence (OSL) dosimeters. By using multiple-teeth samples in combination
      with a custom-built sensitive OSL reader, (60)Co-equivalent doses below 0.64 Gy
      were measured immediately after exposure with the lowest value being 27 mGy for
      the most sensitive sample. The variability of OSL sensitivity, from individual to
      individual using multiple-teeth samples, was determined to be 53%. X-ray and beta
      exposure were found to produce OSL curves with the same shape that differed from
      those due to ultraviolet (UV) exposure; as a result, correlation was observed
      between OSL signals after X-ray and beta exposure and was absent if compared to
      OSL signals after UV exposure. Fading of the OSL signal was "typical" for most
      teeth with just a few of incisors showing atypical behavior. Typical fading
      dependences were described by a bi-exponential decay function with "fast" (decay
      time around of 12 min) and "slow" (decay time about 14 h) components. OSL
      detection limits, based on the techniques developed to-date, were found to be
      satisfactory from the point-of-view of medical triage requirements if conducted
      within 24 hours of the exposure.

PMID- 21949480
TI  - Q(gamma-H2AX), an analysis method for partial-body radiation exposure using gamma
      H2AX in nonhuman primate lymphocytes.
AB  - We previously used the gamma-H2AX assay as a biodosimeter for total-body
      irradiation (TBI) exposure (gamma-rays) in a rhesus macaque (Macaca mulatta)
      model. Utilizing peripheral blood lymphocytes and plucked hairs, we obtained
      statistically significant gamma-H2AX responses days after total-body exposure to
      1-8.5 Gy ((60)Co gamma-rays at 55 cGy min(-1)). Here, we introduce a partial-body
      exposure analysis method, Q(gamma-H2AX), which is based on the number of gamma
      H2AX foci per damaged cells as evident by having one or more gamma-H2AX foci per
      cell. Results from the rhesus monkey - TBI study were used to establish Q(gamma
      H2AX) dose-response calibration curves to assess acute partial-body exposures.
      gamma-H2AX foci were detected in plucked hairs for several days after in vivo
      irradiation demonstrating this assay's utility for dose assessment in various
      body regions. The quantitation of gamma-H2AX may provide a robust biodosimeter
      for analyzing partial body exposures to ionizing radiation in humans.

PMID- 21949481
TI  - A Framework for Comparative Evaluation of Dosimetric Methods to Triage a Large
      Population Following a Radiological Event.
AB  - BACKGROUND: To prepare for a possible major radiation disaster involving large
      numbers of potentially exposed people, it is important to be able to rapidly and
      accurately triage people for treatment or not, factoring in the likely conditions
      and available resources. To date, planners have had to create guidelines for
      triage based on methods for estimating dose that are clinically available and
      which use evidence extrapolated from unrelated conditions. Current guidelines
      consequently focus on measuring clinical symptoms (e.g., time-to-vomiting), which
      may not be subject to the same verification of standard methods and validation
      processes required for governmental approval processes of new and modified
      procedures. Biodosimeters under development have not yet been formally approved
      for this use. Neither set of methods has been tested in settings involving large
      scale populations at risk for exposure.  OBJECTIVE: To propose a framework for
      comparative evaluation of methods for such triage and to evaluate biodosimetric
      methods that are currently recommended and new methods as they are developed. 
      METHODS: We adapt the NIH model of scientific evaluations and sciences needed for
      effective translational research to apply to biodosimetry for triaging very large
      populations following a radiation event. We detail criteria for translating basic
      science about dosimetry into effective multi-stage triage of large populations
      and illustrate it by analyzing 3 current guidelines and 3 advanced methods for
      biodosimetry.  CONCLUSIONS: This framework for evaluating dosimetry in large
      populations is a useful technique to compare the strengths and weaknesses of
      different dosimetry methods. It can help policy-makers and planners not only to
      compare the methods' strengths and weaknesses for their intended use but also to
      develop an integrated approach to maximize their effectiveness. It also reveals
      weaknesses in methods that would benefit from further research and evaluation.

PMID- 21949482
TI  - Biological Dosimetry by the Triage Dicentric Chromosome Assay - Further
      validation of International Networking.
AB  - Biological dosimetry is an essential tool for estimating radiation doses received
      to personnel when physical dosimetry is not available or inadequate. The current
      preferred biodosimetry method is based on the measurement of radiation-specific
      dicentric chromosomes in exposed individuals' peripheral blood lymphocytes.
      However, this method is labour-, time- and expertise-demanding. Consequently, for
      mass casualty applications, strategies have been developed to increase its
      throughput. One such strategy is to develop validated cytogenetic biodosimetry
      laboratory networks, both national and international. In a previous study, the
      dicentric chromosome assay (DCA) was validated in our cytogenetic biodosimetry
      network involving five geographically dispersed laboratories. A complementary
      strategy to further enhance the throughput of the DCA among inter-laboratory
      networks is to use a triage DCA where dose assessments are made by truncating the
      labour-demanding and time-consuming metaphase-spread analysis to 20 to 50
      metaphase spreads instead of routine 500 to 1000 metaphase spread analysis. Our
      laboratory network also validated this triage DCA, however, these dose estimates
      were made using calibration curves generated in each laboratory from the blood
      samples irradiated in a single laboratory. In an emergency situation, dose
      estimates made using pre-existing calibration curves which may vary according to
      radiation type and dose rate and therefore influence the assessed dose. Here, we
      analyze the effect of using a pre-existing calibration curve on assessed dose
      among our network laboratories. The dose estimates were made by analyzing 1000
      metaphase spreads as well as triage quality scoring and compared to actual
      physical doses applied to the samples for validation. The dose estimates in the
      laboratory partners were in good agreement with the applied physical doses and
      determined to be adequate for guidance in the treatment of acute radiation
      syndrome.

PMID- 21949484
TI  - Polygyny and HIV in Malawi.
AB  - We review the relationship between polygyny and HIV and identify a positive
      individual-level correlation, and a negative ecological correlation. We
      subsequently examine two mechanisms that contribute to the individual-level
      correlation. First, we find that men in polygynous marriages have more
      extramarital sex than men in monogamous unions (both in terms of self reports and
      in terms of spousal reports of the suspicion of adultery). Second, we find
      evidence of adverse selection of HIV positive women into polygynous unions via an
      investigation of the relationship between marriage order and polygyny status. We
      conclude with reflections about possible explanations for the distinct individual
      and ecological correlations.

PMID- 21949483
TI  - Differential Effects of Ventricular Pacing Sites of Contraction Synchrony and
      Global Cardiac Performance.
AB  - BACKGROUND: Quantification of left ventricular (LV) dyssynchrony allows for
      objective measures of resynchronization therapy (CRT) effectiveness. We tested
      the hypothesis that site of LV pacing, fusion beats and baseline contractility
      alter contraction synchrony as quantified by regional and global measures of LV
      performance.  METHODS AND RESULTS: In 8 open-chested pentobarbital-anesthetized
      canine preparations we compared the effects of right atrial (RA), RA-high right
      ventricular (RV) free wall, as a model of left bundle branch block contraction
      pattern, RA-LV apex (LVa), RA-LV free wall (LVfw), and RA-RV-apical LV (CRTa) and
      RA-RV-free wall LV (CRTfw), as CRT. LV pressure-volume loops recorded using high
      fidelity pressure and conductance catheters and echocardiographic angle-corrected
      color-coded strain imaging of mid-LV short axis views analyzed radial strain from
      six segments. To control for contractile state esmolol-induced beta blockage was
      studied, and in 5 dogs to control for RA and ventricular pacing fusion beat
      artifacts, repeat studies were done following AV node ablation. RA-RV pacing
      reduced stroke work (SW) (57+/-18 to 33+/-13* mmHg.mL,*p<0.05 vs RA pacing),
      decreased LV end-diastolic volume and induced marked radial dyssynchrony (maximal
      time difference between peak segmental strain) from 31+/-15 to 234+/-60* ms.
      Changes in radial dyssynchrony correlated significantly with changes in SW (r=
      0.53, p<0.01). Dyssynchrony improved with both CRTa and CRTfw (69*+/-31 and 98*+/
      63 ms, respectively) while SW only improved with CRTa (62+/-22* and 37+/-13
      mmHg.mL, respectively * p<0.05 vs RV pacing). CRTa also tended to increased LV
      end-diastolic volume over RA-RV. Esmolol slowed HR from 118+/-10 to 108+/-10
      beats/min* and tended to decrease contractility (end-systolic elastance (Ees)
      from 12.1+/-7.9 to 8.9+/-3.9 mmHg/ml, p=0.167) but did not alter the degree of RV
      pacing induced dyssynchrony. AV ablation had no effect on the observed apical and
      free wall contraction differences seen during baseline conditions.  CONCLUSION:
      Although both CRTa and CRTfw reduced contraction dyssynchrony, CRTa tended to
      improve global LV performance more by increasing end-diastolic volume. Thus, CRT
      may improve global LV performance differently, depending on the LV pacing site.

PMID- 21949485
TI  - Surface Plasmon Polariton Excitation in Metallic Layer Via Surface Relief
      Gratings in Photoactive Polymer Studied by the Finite-Difference Time-Domain
      Method.
AB  - We performed numerical investigations of surface plasmon excitation and
      propagation in structures made of a photochromic polymer layer deposited over a
      metal surface using the finite-difference time-domain method. We investigated the
      process of light coupling into surface plasmon polariton excitation using surface
      relief gratings formed on the top of a polymer layer and compared it with the
      coupling via rectangular ridges grating made directly in the metal layer. We also
      performed preliminary studies on the influence of refractive index change of
      photochromic polymer on surface plasmon polariton propagation conditions.

PMID- 21949486
TI  - Determining eligibility for long-term care-lessons from Germany.
AB  - OBJECTIVES: This paper addresses recent steps for reforming the eligibility
      criteria of the German long-term care insurance that have been initiated to
      overcome shortcomings in the current system. METHODS: Based on findings of a
      survey of international long-term care systems, assessment tools and the relevant
      literature on care needs a new tool for determining eligibility in the German
      long-term care insurance was developed. RESULTS: The new tool for determining
      long-term care eligibility broadens the understanding of what 'dependency on
      nursing care' implies for the person affected. The assessment results in a degree
      of dependency from personal help provided by formal or informal caregivers. This
      degree of dependency can be used for determining eligibility for and the amount
      of long-term care benefits. DISCUSSION: The broader understanding of 'dependency
      on nursing care' and the new tool are important steps to adapt the German long
      term care insurance to the challenges of the demographic and societal changes in
      the future.

PMID- 21949487
TI  - What happens to quality in integrated homecare? A 15-year follow-up study.
AB  - OBJECTIVES: To explore the impact of structural integration on homecare quality.
      METHODS: A case study in an organisation comprising a before-after comparison
      with baseline and four follow-up measurements during 1994-2009, using interviews
      with clients (n=66-84) and postal inquiries to relatives (n=73-78) and staff
      (n=68-136). RESULTS: Despite the organisational reform involving extensive
      mergers of health and social care organisations and cuts in staff and service
      provision, homecare quality remained at almost the same level throughout the 15
      year follow-up. According to the clients, it even slightly improved in some
      homecare areas. CONCLUSIONS: The results show that despite the structural
      integration and cuts in staff and service provision, the quality of homecare
      remained at a good level. Assuming that the potential confounders did have
      inhibiting effects, the results suggest that structural integration had a
      positive impact on homecare quality. To obtain firmer evidence to support this
      tentative conclusion, further research with a randomised comparison design is
      needed.

PMID- 21949488
TI  - Integrate now, create health.

PMID- 21949489
TI  - Do 'virtual wards' reduce rates of unplanned hospital admissions, and at what
      cost? A research protocol using propensity matched controls.
AB  - BACKGROUND: This retrospective study will assess the extent to which
      multidisciplinary case management in the form of virtual wards (VWs) leads to
      changes in the use of health care and social care by patients at high risk of
      future unplanned hospital admission. VWs use the staffing, systems and daily
      routines of a hospital ward to deliver coordinated care to patients in their own
      homes. Admission to a VW is offered to patients identified by a predictive risk
      model as being at high risk of unplanned hospital admission in the coming 12
      months. STUDY DESIGN AND DATA COLLECTION METHODS: We will compare the health care
      and social care use of VW patients to that of matched controls. Controls will be
      drawn from (a) national, and (b) local, individual-level pseudonymous routine
      data. The costs of setting up and running a VW will be determined from the
      perspectives of both health and social care organizations using a combination of
      administrative data, interviews and diaries. METHODS OF ANALYSIS: Using
      propensity score matching and prognostic matching, we will create matched
      comparator groups to estimate the effect size of virtual wards in reducing
      unplanned hospital admissions. CONCLUSIONS: THIS STUDY WILL ALLOW US TO DETERMINE
      RELATIVE TO MATCHED COMPARATOR GROUPS: whether VWs reduce the use of emergency
      hospital care; the impact, if any, of VWs on the uptake of primary care,
      community health services and council-funded social care; and the potential costs
      and savings of VWs from the perspectives of the national health service (NHS) and
      local authorities.

PMID- 21949490
TI  - A multi-site, randomized study of strengths-based case management with substance
      abusing parolees.
AB  - OBJECTIVES: To test whether strengths-based case management provided during an
      inmate's transition from incarceration to the community increases participation
      in community substance abuse treatment, enhances access to needed social
      services, and improves drug use, crime, and HIV risk outcomes.  METHODS: In a
      multi-site trial, inmates (men and women) in four states (n = 812) were randomly
      assigned (within site) to receive either Transitional Case Management (TCM
      group), based on strengths-based principles, or standard parole services (SR
      group). Data were collected at baseline and at 3 and 9 months following release
      from prison. Analyses compared the two groups with respect to services received
      and to drug use, crime, and HIV risk behavior outcomes.  RESULTS: There were no
      significant differences between parolees in the TCM group and the SR group on
      outcomes related to participation in drug abuse treatment, receipt of social
      services, or drug use, crime, and HIV risk behaviors. For specific services
      (e.g., residential treatment, mental health), although significant differences
      were found for length of participation or for number of visits, the number of
      participants in these services was small and the direction of effect was not
      consistent.  CONCLUSION: In contrast to positive findings in earlier studies of
      strengths-based case management with mental-health and drug-abuse clients, this
      study found that case management did not improve treatment participation or
      behavioral outcomes for parolees with drug problems. The discussion includes
      possible reasons for the findings and suggestions for modifications to the
      intervention that could be addressed in future research.

PMID- 21949491
TI  - Quantitative metabolomics based on gas chromatography mass spectrometry: status
      and perspectives.
AB  - Metabolomics involves the unbiased quantitative and qualitative analysis of the
      complete set of metabolites present in cells, body fluids and tissues (the
      metabolome). By analyzing differences between metabolomes using biostatistics
      (multivariate data analysis; pattern recognition), metabolites relevant to a
      specific phenotypic characteristic can be identified. However, the reliability of
      the analytical data is a prerequisite for correct biological interpretation in
      metabolomics analysis. In this review the challenges in quantitative metabolomics
      analysis with regards to analytical as well as data preprocessing steps are
      discussed. Recommendations are given on how to optimize and validate
      comprehensive silylation-based methods from sample extraction and derivatization
      up to data preprocessing and how to perform quality control during metabolomics
      studies. The current state of method validation and data preprocessing methods
      used in published literature are discussed and a perspective on the future
      research necessary to obtain accurate quantitative data from comprehensive GC-MS
      data is provided.

PMID- 21949493
TI  - Metabolic profiling of HepG2 cells incubated with S(-) and R(+) enantiomers of
      anti-coagulating drug warfarin.
AB  - Warfarin is a commonly prescribed oral anticoagulant with narrow therapeutic
      index. It achieves anti-coagulating effects by interfering with the vitamin K
      cycle. Warfarin has two enantiomers, S(-) and R(+) and undergoes stereoselective
      metabolism, with the S(-) enantiomer being more effective. We reported the
      intracellular metabolic profile in HepG2 cells incubated with S(-) and R(+)
      warfarin by GCMS. Chemometric method PCA was applied to analyze the individual
      samples. A total of 80 metabolites which belong to different categories were
      identified. Two batches of experiments (with and without the presence of vitamin
      K) were designed. In samples incubated with S(-) and R(+) warfarin, glucuronic
      acid showed significantly decreased in cells incubated with R(+) warfarin but not
      in those incubated with S(-) warfarin. It may partially explain the lower bio
      activity of R(+) warfarin. And arachidonic acid showed increased in cells
      incubated with S(-) warfarin but not in those incubated with R(+) warfarin. In
      addition, a number of small molecules involved in gamma-glutamyl cycle displayed
      ratio variations. Intracellular glutathione detection further validated the
      results. Taken together, our findings provided molecular evidence on a
      comprehensive metabolic profile on warfarin-cell interaction which may shed new
      lights on future improvement of warfarin therapy. ELECTRONIC SUPPLEMENTARY
      MATERIAL: The online version of this article (doi:10.1007/s11306-010-0262-3)
      contains supplementary material, which is available to authorized users.

PMID- 21949492
TI  - Bioinformatics tools for cancer metabolomics.
AB  - It is well known that significant metabolic change take place as cells are
      transformed from normal to malignant. This review focuses on the use of different
      bioinformatics tools in cancer metabolomics studies. The article begins by
      describing different metabolomics technologies and data generation techniques.
      Overview of the data pre-processing techniques is provided and multivariate data
      analysis techniques are discussed and illustrated with case studies, including
      principal component analysis, clustering techniques, self-organizing maps,
      partial least squares, and discriminant function analysis. Also included is a
      discussion of available software packages.

PMID- 21949494
TI  - Degradation of a benzene-toluene mixture by hydrocarbon-adapted bacterial
      communities.
AB  - We examined the rate of degradation of a benzene-toluene mixture in aerobic
      microcosms prepared with samples of an aquifer that lies below a petrochemical
      plant (SIReN, UK). Five samples exposed to different concentrations of benzene
      (from 0.6 to 317 mg l(-1)) were used. Fast degradation (approx. 1-6 mg l(-1) day(
      1)) of both contaminants was observed in all groundwater samples and complete
      degradation was recorded by the seventh day except for one sample. We also
      identified the microbial community in each of the samples by culture-independent
      techniques. Two of the less impacted samples harbour the aerobic benzene degrader
      Pseudomonas fluorescens, while Acidovorax and Arthrobacter spp. were found in the
      most polluted sample and are consistent with the population observed in situ.
      Hydrogenophaga was found in the deepest sample while Rhodoferax spp. were
      recovered in an alkaline sample (pH 8.4) and may also be implicated in benzene
      degradation. Time series analysis shows that each of the samples has a different
      community but they remain stable over the degradation period. This study provides
      new information on a well not previously studied (no. 309s) and confirms that
      adapted communities have the ability to degrade hydrocarbon mixtures and could be
      used in further bioaugmentation approaches in contaminated sites.

PMID- 21949495
TI  - Improvement of sexual function after transobturator tape procedure in women with
      stress urinary incontinence.
AB  - Sling procedures are a widely proven treatment for stress urinary incontinence.
      The aim of this prospective study was to evaluate the effect of the
      transobturator tape on female sexual functioning. Fifty-four women treated for
      stress urinary incontinence with transobturator tape filled out self-administered
      questionnaires on quality of life, urinary incontinence, and sexual function
      prior to surgery and 6 weeks and 12 months postoperatively. Preoperatively, 40
      women (78%) were sexually active. There were no significant postoperative changes
      regarding frequency of sexual activity, sexual desire, and problems with
      lubrication or orgasm. Preoperatively, 55% reported urinary leakage during sexual
      activity and after surgery 6.5%. Sexual satisfaction was significantly improved 6
      weeks (p = 0.05) and 12 months (p = 0.03) postoperatively. Pain during or after
      sexual activity was declined, only one patient reported worsening of pain. The
      transobturator tape procedure has a positive effect on female sexual functioning
      by reducing urinary leakage and pain during or after sexual activity. It seems to
      improve the overall sexual satisfaction. Further research is warranted to support
      these preliminary findings.

PMID- 21949496
TI  - Identifying sources of strength: resilience from the perspective of older people
      receiving long-term community care.
AB  - This study seeks to explore the sources of strength giving rise to resilience
      among older people. Twenty-nine in-depth interviews were conducted with older
      people who receive long-term community care. The interviews were subjected to a
      thematic content analysis. The findings suggest that the main sources of strength
      identified among older people were constituted on three domains of analysis; the
      individual-, interactional and contextual domain. The individual domain refers to
      the qualities within older people and comprises of three sub-domains, namely
      beliefs about one's competence, efforts to exert control and the capacity to
      analyse and understand ones situation. Within these subdomains a variety of
      sources of strength were found like pride about ones personality, acceptance and
      openness about ones vulnerability, the anticipation on future losses, mastery by
      practising skills, the acceptance of help and support, having a balanced vision
      on life, not adapting the role of a victim and carpe-diem. The interactional
      domain is defined as the way older people cooperate and interact with others to
      achieve their personal goals. Sources of strength on this domain were empowering
      (in)formal relationships and the power of giving. Lastly, the contextual domain
      refers to a broader political-societal level and includes sources of strength
      like the accessibility of care, the availability of material resources and social
      policy. The three domains were found to be inherently linked to each other. The
      results can be used for the development of positive, proactive interventions
      aimed at helping older people build on the positive aspects of their lives.

PMID- 21949497
TI  - Control of Nanoscale Environment to Improve Stability of Immobilized Proteins on
      Diamond Surfaces.
AB  - Immunoassays for detection of bacterial pathogens rely on the selectivity and
      stability of bio-recognition elements such as antibodies tethered to sensor
      surfaces. The search for novel surfaces that improve the stability of
      biomolecules and assay performance has been pursued for a long time. However, the
      anticipated improvements in stability have not been realized in practice under
      physiological conditions because the surface functionalization layers on commonly
      used substrates, silica and gold, are themselves unstable on time scales of days.
      In this paper, we show that covalent linking of antibodies to diamond surfaces
      leads to substantial improvements in biological activity of proteins as measured
      by the ability to selectively capture cells of the pathogenic bacterium
      Escherichia coli O157:H7 even after exposure to buffer solutions at 37  degrees C
      for extended periods of time, approaching 2 weeks. Our results from ELISA, XPS,
      fluorescence microscopy, and MD simulations suggest that by using highly stable
      surface chemistry and controlling the nanoscale organization of the antibodies on
      the surface, it is possible to achieve significant improvements in biological
      activity and stability. Our findings can be easily extended to functionalization
      of micro and nanodimensional sensors and structures of biomedical diagnostic and
      therapeutic interest.

PMID- 21949498
TI  - Coagulase gene polymorphism of Staphylococcus aureus isolated from clinical and
      sub-clinical bovine mastitis in Isfahan and Chaharmahal va Bakhtiari provinces of
      Iran.
AB  - Mastitis is a common disease in dairy cattle and is an inflammatory response of
      the breast tissue to bacterial attack to this tissue. Mastitis causes
      considerable loss to the dairy industry, among the several bacterial pathogens
      that can cause mastitis; Staphylococcus aureus is probably the most lethal agent
      because it causes chronic and deep infection in the mammary glands that is
      extremely difficult to cure. Several virulence factors including coagulase gene
      are produced by S. aureus and may contribute to its pathogenicity. This study was
      conducted to investigate the coagulase gene polymorphism of S. aureus isolated
      from clinical and sub-clinical bovine mastitis milk samples in Isfahan and
      Chaharmahal va Bakhtiari provinces of Iran. Amplification of the coagulase gene
      from 86 S. aureus strains isolates by specific primers showed 31 specimens
      contained 970 bp fragment, and 11 strains contained 730 bp fragment relevant to
      coa gene (coagulase) in PCR. After enzymatic digestion with AluI, 31 specimens
      contained three bands: 320, 490, and 160 bp (genotype I) and 11 specimens
      contained two bands: 490 and 240 bp (genotype VIII) in the RFLP.

PMID- 21949499
TI  - Climate change effects on human health in a gender perspective: some trends in
      Arctic research.
AB  - BACKGROUND: Climate change and environmental pollution have become pressing
      concerns for the peoples in the Arctic region. Some researchers link climate
      change, transformations of living conditions and human health. A number of
      studies have also provided data on differentiating effects of climate change on
      women's and men's well-being and health. OBJECTIVE: To show how the issues of
      climate and environment change, human health and gender are addressed in current
      research in the Arctic. The main purpose of this article is not to give a full
      review but to draw attention to the gaps in knowledge and challenges in the
      Arctic research trends on climate change, human health and gender. METHODS: A
      broad literature search was undertaken using a variety of sources from natural,
      medical, social science and humanities. The focus was on the keywords. RESULTS:
      Despite the evidence provided by many researchers on differentiating effects of
      climate change on well-being and health of women and men, gender perspective
      remains of marginal interest in climate change, environmental and health studies.
      At the same time, social sciences and humanities, and gender studies in
      particular, show little interest towards climate change impacts on human health
      in the Arctic. As a result, we still observe the division of labour between
      disciplines, the disciplinary-bound pictures of human development in the Arctic
      and terminology confusion. CONCLUSION: Efforts to bring in a gender perspective
      in the Arctic research will be successful only when different disciplines would
      work together. Multidisciplinary research is a way to challenge
      academic/disciplinary homogeneity and their boundaries, to take advantage of the
      diversity of approaches and methods in production of new integrated knowledge.
      Cooperation and dialogue across disciplines will help to develop adequate
      indicators for monitoring human health and elaborating efficient policies and
      strategies to the benefit of both women and men in the Arctic.

PMID- 21949500
TI  - What about healthy participants? The improvement and deterioration of self
      reported health at a 10-year follow-up of the Vasterbotten Intervention
      Programme.
AB  - AIM: The Vasterbotten Intervention Programme (VIP) addresses cardiovascular
      disease and diabetes in the middle-aged population of Vasterbotten County,
      Sweden. Self-reported health (SRH) is one of the risk factors for both
      conditions. The aim of this study was to analyse the development patterns of SRH
      among the VIP participants. METHODS: Cross-sectional data from 1990 to 2007 were
      used to analyse the prevalence of poor SRH among 101,396 VIP participants aged 40
      60 years. Panel data were used to study the change in SRH among 25,695 persons
      aged 30-60 years, who participated in the VIP twice within a 10-year interval.
      RESULTS: Prevalence of poor SRH fluctuated between 1990 and 2007 in Vasterbotten
      County. There was a temporary decline around 2000, with SRH continuously
      improving thereafter. The majority of panel participants remained in good SRH;
      over half of those with poor or fair SRH at baseline reported better SRH at
      follow-up. SRH declined in 19% of the panel participants, mostly among those who
      had good SRH at the baseline. The decline was common among both women and men, in
      all educational, age and marital status groups. CONCLUSIONS: The SRH improvement
      among those with poor and fair SRH at baseline suggests that VIP has been
      successful in addressing its target population. However, the deterioration of SRH
      among 21% of the individuals with good SRH at baseline is of concern. From a
      public health perspective, it is important for health interventions to address
      not only the risk group but also those with a healthy profile to prevent the
      negative development among the seemingly healthy participants.

PMID- 21949501
TI  - Interactions of AChE with Abeta Aggregates in Alzheimer's Brain: Therapeutic
      Relevance of IDN 5706.
AB  - Acetylcholinesterase (AChE; EC 3.1.1.7) plays a crucial role in the rapid
      hydrolysis of the neurotransmitter acetylcholine, in the central and peripheral
      nervous system and might also participate in non-cholinergic mechanism related to
      neurodegenerative diseases. Alzheimer's disease (AD) is a neurodegenerative
      disorder characterized by a progressive deterioration of cognitive abilities,
      amyloid-beta (Abeta) peptide accumulation and synaptic alterations. We have
      previously shown that AChE is able to accelerate the Abeta peptide assembly into
      Alzheimer-type aggregates increasing its neurotoxicity. Furthermore, AChE
      activity is altered in brain and blood of Alzheimer's patients. The enzyme
      associated to amyloid plaques changes its enzymatic and pharmacological
      properties, as well as, increases its resistant to low pH, inhibitors and excess
      of substrate. Here, we reviewed the effects of IDN 5706, a hyperforin derivative
      that has potential preventive effects on the development of AD. Our results show
      that treatment with IDN 5706 for 10 weeks increases brain AChE activity in 7
      month-old double transgenic mice (APP(SWE)-PS1) and decreases the content of AChE
      associated with different types of amyloid plaques in this Alzheimer's model. We
      concluded that early treatment with IDN 5706 decreases AChE-Abeta interaction and
      this effect might be of therapeutic interest in the treatment of AD.

PMID- 21949502
TI  - Proinsulin: from hormonal precursor to neuroprotective factor.
AB  - In the last decade, non-canonical functions have been described for several
      molecules with hormone-like activities in different stages of vertebrate
      development. Since its purification in the 1960s, proinsulin has been one of the
      best described hormonal precursors, though it has been overwhelmingly studied in
      the context of insulin, the mature protein secreted by the pancreas. Beginning
      with our discovery of the presence and precise regulation of proinsulin mRNA in
      early neurulation and neurogenesis, we uncovered a role for proinsulin in cell
      survival in the developing nervous system. We subsequently demonstrated the
      ability of proinsulin to prevent pathological cell death and delay photoreceptor
      degeneration in a mouse model of retinitis pigmentosa. In this review, we focus
      on the evolution of proinsulin/insulin, beginning with insulin-like peptides
      expressed in mainly the neurosecretory cells of some invertebrates. We summarize
      findings related to the regulation of proinsulin expression during development
      and discuss the possible effects of proinsulin in neural cells or tissue, and its
      potential as a neuroprotective molecule.

PMID- 21949504
TI  - Parallel readout of pathway-specific inputs to laminated brain structures.
AB  - Local field potentials (LFPs) capture the electrical activity produced by
      principal cells during integration of converging synaptic inputs from multiple
      neuronal populations. However, since synaptic currents mix in the extracellular
      volume, LFPs have complex spatiotemporal structure, making them hard to exploit.
      Here we propose a biophysical framework to identify and separate LFP-generators.
      First we use a computational multineuronal model that scales up single cell
      electrogenesis driven by several synaptic inputs to realistic aggregate LFPs.
      This approach relies on the fixed but distinct locations of synaptic inputs from
      different presynaptic populations targeting a laminated brain structure. Thus the
      LFPs are contributed by several pathway-specific LFP-generators, whose electrical
      activity is defined by the spatial distribution of synaptic terminals and the
      time course of synaptic currents initiated in target cells by the corresponding
      presynaptic population. Then we explore the efficacy of independent component
      analysis to blindly separate converging sources and reconstruct pathway-specific
      LFP-generators. This approach can optimally locate synaptic inputs with
      subcellular accuracy while the reconstructed time course of pathway-specific LFP
      generators is reliable in the millisecond scale. We also describe few cases where
      the non-linear intracellular interaction of strongly overlapping LFP-generators
      may lead to a significant cross-contamination and the appearance of derivative
      generators. We show that the approach reliably disentangle ongoing LFPs in the
      hippocampus into contribution of several LFP-generators. We were able to readout
      in parallel the pathway-specific presynaptic activity of projection cells in the
      entorhinal cortex and pyramidal cells in the ipsilateral and contralateral CA3.
      Thus we provide formal mathematical and experimental support for parallel readout
      of the activity of converging presynaptic populations in working neuronal
      circuits from common LFPs.

PMID- 21949503
TI  - Revisiting the Role of Acetylcholinesterase in Alzheimer's Disease: Cross-Talk
      with P-tau and beta-Amyloid.
AB  - A common feature in the Alzheimer's disease (AD) brain is the presence of
      acetylcholinesterase (AChE) which is commonly associated with beta-amyloid
      plaques and neurofibrillary tangles (NFT). Although our understanding of the
      relationship between AChE and the pathological features of AD is incomplete,
      increasing evidence suggests that both beta-amyloid protein (Abeta) and
      abnormally hyperphosphorylated tau (P-tau) can influence AChE expression. We also
      review recent findings which suggest the possible role of AChE in the development
      of a vicious cycle of Abeta and P-tau dysregulation and discuss the limited and
      temporary effect of therapeutic intervention with AChE inhibitors.

PMID- 21949505
TI  - Slow potentials in time estimation: the role of temporal accumulation and
      habituation.
AB  - Numerous studies have shown that contingent negative variation (CNV) measured at
      fronto-central and parietal-central areas is closely related to interval timing.
      However, the exact nature of the relation between CNV and the underlying timing
      mechanisms is still a topic of discussion. On the one hand, it has been proposed
      that the CNV measured at supplementary motor area (SMA) is a direct reflection of
      the unfolding of time since a perceived onset, whereas other work has suggested
      that the increased amplitude reflects decision processes involved in interval
      timing. Strong evidence for the first view has been reported by Macar et al.
      (1999), who showed that variations in temporal performance were reflected in the
      measured CNV amplitude. If the CNV measured at SMA is a direct function of the
      passing of time, habituation effects are not expected. Here we report two
      replication studies, which both failed to replicate the expected performance
      dependent variations. Even more powerful linear-mixed effect analyses failed to
      find any performance related effects on the CNV amplitude, whereas habituation
      effects were found. These studies therefore suggest that the CNV amplitude does
      not directly reflect the unfolding of time.

PMID- 21949506
TI  - Effects of endocannabinoid system modulation on cognitive and emotional behavior.
AB  - Cannabis has long been known to produce cognitive and emotional effects. Research
      has shown that cannabinoid drugs produce these effects by driving the brain's
      endogenous cannabinoid system and that this system plays a modulatory role in
      many cognitive and emotional processes. This review focuses on the effects of
      endocannabinoid system modulation in animal models of cognition (learning and
      memory) and emotion (anxiety and depression). We review studies in which natural
      or synthetic cannabinoid agonists were administered to directly stimulate
      cannabinoid receptors or, conversely, where cannabinoid antagonists were
      administered to inhibit the activity of cannabinoid receptors. In addition,
      studies are reviewed that involved genetic disruption of cannabinoid receptors or
      genetic or pharmacological manipulation of the endocannabinoid-degrading enzyme,
      fatty acid amide hydrolase (FAAH). Endocannabinoids affect the function of many
      neurotransmitter systems, some of which play opposing roles. The diversity of
      cannabinoid roles and the complexity of task-dependent activation of neuronal
      circuits may lead to the effects of endocannabinoid system modulation being
      strongly dependent on environmental conditions. Recent findings are reviewed that
      raise the possibility that endocannabinoid signaling may change the impact of
      environmental influences on emotional and cognitive behavior rather than
      selectively affecting any specific behavior.

PMID- 21949507
TI  - Adverse Associations between Visceral Adiposity, Brain Structure, and Cognitive
      Performance in Healthy Elderly.
AB  - The link between central adiposity and cognition has been established by indirect
      measures such as body mass index (BMI) or waist-hip ratio. Magnetic resonance
      imaging (MRI) quantification of central abdominal fat has been linked to elevated
      risk of cardiovascular and cerebro-vascular disease. However it is not known how
      quantification of visceral fat correlates with cognitive performance and measures
      of brain structure. We filled this gap by characterizing the relationships
      between MRI measures of abdominal adiposity, brain morphometry, and cognition, in
      healthy elderly. METHODS: A total of 184 healthy community dwelling elderly
      subjects without cognitive impairment participated in this study. Anthropometric
      and biochemical markers of cardiovascular risk, neuropsychological measurements
      as well as MRI of the brain and abdomen fat were obtained. Abdominal images were
      segmented into subcutaneous adipose tissue and visceral adipose tissue (VAT)
      adipose tissue compartments. Brain MRI measures were analyzed quantitatively to
      determine total brain volume, hippocampal volume, ventricular volume, and
      cortical thickness. RESULTS: VAT showed negative association with verbal memory
      (r = 0.21, p = 0.005) and attention (r = 0.18, p = 0.01). Higher VAT was
      associated with lower hippocampal volume (F = 5.39, p = 0.02) and larger
      ventricular volume (F = 6.07, p = 0.02). The participants in the upper quartile
      of VAT had the lowest hippocampal volume even after adjusting for age, gender,
      hypertension, and BMI (b = -0.28, p = 0.005). There was a significant age by VAT
      interaction for cortical thickness in the left prefrontal region. CONCLUSION: In
      healthy older adults, elevated VAT is associated with negative effects on
      cognition, and brain morphometry.

PMID- 21949508
TI  - Regulation of villin by wnt5a/ror2 signaling in human intestinal cells.
AB  - Regulation of expression of the intestinal epithelial actin-binding protein,
      villin, is poorly understood. The aim of this study was to determine whether
      Wnt5a stimulates Ror2 in intestinal epithelia caused transient increases in
      phospho-ERK1/2 (pERK1/2) and subsequently increased expression of villin
      transcript and protein. To demonstrate Wnt5a-Ror2 regulation of villin
      expression, we overexpressed wild-type, truncated, or mutant Ror2 constructs in
      HT29 adenocarcinoma cells and non-transformed fetally derived human intestinal
      epithelial cells, added conditioned media containing Wnt5a and measured changes
      in ERK1/2 phosphorylation, villin amplicons, and protein expression by RT-PCR and
      Western blot techniques. Wnt5a addition caused a transient increase in pERK1/2,
      which was maximal at 10 min but extinguished by 30 min. Transient transfection
      with a siRNA duplex against Ror2 diminished Ror2 amplicons and protein and
      reduced the extent of pERK1/2 activation. Structure-function analysis revealed
      that the deletion of the cysteine-rich, kringle, or tyrosine kinase domain or
      substitution mutations of tyrosine residues in the intracellular Ser/Thr-1 region
      of Ror2 prevented the Wnt5a stimulation of pERK1/2. Deletion of the intracellular
      proline and serine/threonine-rich regions of Ror2 had no effect on Wnt5a
      stimulation of pERK1/2. The increase in villin expression was blocked by
      pharmacological inhibition of MEK-1 and casein kinase 1, but not by PKC and p38
      inhibitors. Neither Wnt3a nor epidermal growth factor addition caused increases
      in villin protein. Our findings suggest that Wnt5a/Ror2 signaling can regulate
      villin expression in the intestine.

PMID- 21949509
TI  - How linguistic chickens help spot spoken-eggs: phonological constraints on speech
      identification.
AB  - It has long been known that the identification of aural stimuli as speech is
      context-dependent (Remez et al., 1981). Here, we demonstrate that the
      discrimination of speech stimuli from their non-speech transforms is further
      modulated by their linguistic structure. We gauge the effect of phonological
      structure on discrimination across different manifestations of well-formedness in
      two distinct languages. One case examines the restrictions on English syllables
      (e.g., the well-formed melif vs. ill-formed mlif); another investigates the
      constraints on Hebrew stems by comparing ill-formed AAB stems (e.g., TiTuG) with
      well-formed ABB and ABC controls (e.g., GiTuT, MiGuS). In both cases, non-speech
      stimuli that conform to well-formed structures are harder to discriminate from
      speech than stimuli that conform to ill-formed structures. Auxiliary experiments
      rule out alternative acoustic explanations for this phenomenon. In English, we
      show that acoustic manipulations that mimic the mlif-melif contrast do not impair
      the classification of non-speech stimuli whose structure is well-formed (i.e.,
      disyllables with phonetically short vs. long tonic vowels). Similarly, non-speech
      stimuli that are ill-formed in Hebrew present no difficulties to English
      speakers. Thus, non-speech stimuli are harder to classify only when they are well
      formed in the participants' native language. We conclude that the classification
      of non-speech stimuli is modulated by their linguistic structure: inputs that
      support well-formed outputs are more readily classified as speech.

PMID- 21949510
TI  - Unable to conform, unwilling to rebel? Youth, culture, and motivation in
      globalizing Japan.
AB  - This paper investigates the effects of globalization on Japanese young adults
      from sociological and psychological perspectives. While Japan's socio-economic
      institutions have shown mainly resistant (or "hot") reactions to globalization,
      individual-level adaptations remain oriented toward conformity to dominant life
      expectations, which remain largely unchanged, despite decreasing rewards.
      However, a socially withdrawn sub-group (the so-called hikikomori) appears to be
      unable to conform yet is also unwilling to rebel. The experimental evidence we
      review suggests such youth deviate from typical Japanese motivational patterns
      but have not necessarily become more Western. This poses serious problems in an
      interdependence-oriented culture, but the paralysis of this group seems to be an
      outcome of labor market change rather than a psychopathology. Finally, we also
      identify a contrasting group - whom we call the quiet mavericks - that adapts in
      creative and integrative (or "cool") ways by negotiating conformist pressures
      tactfully. Our account sheds light on just how complex and painful the
      psychological and sociological effects of globalization can be for young people
      in conformist societies, with implications to policy and social sustainability.

PMID- 21949511
TI  - Lacan's Construction and Deconstruction of the Double-Mirror Device.
AB  - In the 1950s Jacques Lacan developed a set-up with a concave mirror and a plane
      mirror, based on which he described the nature of human identification. He also
      formulated ideas on how psychoanalysis, qua clinical practice, responds to
      identification. In this paper Lacan's schema of the two mirrors is described in
      detail and the theoretical line of reasoning he aimed to articulate with aid of
      this spatial model is discussed. It is argued that Lacan developed his double
      mirror device to clarify the relationship between the drive, the ego, the ideal
      ego, the ego-ideal, the other, and the Other. This model helped Lacan describe
      the dynamics of identification and explain how psychoanalytic treatment works. He
      argued that by working with free association, psychoanalysis aims to articulate
      unconscious desire, and bypass the tendency of the ego for misrecognition. The
      reasons why Lacan stressed the limits of his double-mirror model and no longer
      considered it useful from the early 1960s onward are examined. It is argued that
      his concept of the gaze, which he qualifies as a so-called "object a," prompted
      Lacan move away from his double-mirror set-up. In those years Lacan gradually
      began to study the tension between drive and signifier. The schema of the two
      mirrors, by contrast, focused on the tension between image and signifier, and
      missed the point Lacan aimed to address in this new era of his work.

PMID- 21949512
TI  - Inhibition and adjective learning in bilingual and monolingual children.
AB  - The ability to control attention - by inhibiting pre-potent, yet no longer
      relevant information - is an essential skill in all of human learning, and
      increasing evidence suggests that this ability is enhanced in language learning
      environments in which the learner is managing and using more than one language.
      One question waiting to be addressed is whether such efficient attentional
      control plays a role in word learning. That is, children who must manage two
      languages also must manage to learn two languages and the advantages of more
      efficient attentional control may benefit aspects of language learning within
      each language. This study compared bilingual and monolingual children's
      performances in an artificial word-learning task and in a non-linguistic task
      that measures attention control. Three-year-old monolingual and bilingual
      children with similar vocabulary development participated in these tasks. The
      results replicate earlier work showing advanced attentional control among
      bilingual children and suggest that this better attentional control may also
      benefit better performance in novel adjective learning. The findings provide the
      first direct evidence of a relation between performances in an artificial word
      learning task and in an attentional control task. We discuss this finding with
      respect to the general relevance of attentional control for lexical learning in
      all children and with respect to current views of bilingual children's word
      learning.

PMID- 21949513
TI  - Do action video games improve perception and cognition?
AB  - Frequent action video game players often outperform non-gamers on measures of
      perception and cognition, and some studies find that video game practice enhances
      those abilities. The possibility that video game training transfers broadly to
      other aspects of cognition is exciting because training on one task rarely
      improves performance on others. At first glance, the cumulative evidence suggests
      a strong relationship between gaming experience and other cognitive abilities,
      but methodological shortcomings call that conclusion into question. We discuss
      these pitfalls, identify how existing studies succeed or fail in overcoming them,
      and provide guidelines for more definitive tests of the effects of gaming on
      cognition.

PMID- 21949514
TI  - Experimental bariatric surgery in rats generates a cytotoxic chemical environment
      in the gut contents.
AB  - Bariatric surgery, also known as metabolic surgery, is an effective treatment for
      morbid obesity, which also offers pronounced metabolic effects including the
      resolution of type 2 diabetes and a decrease in cardiovascular disease and long
      term cancer risk. However, the mechanisms of surgical weight loss and the long
      term consequences of bariatric surgery remain unclear. Bariatric surgery has been
      demonstrated to alter the composition of both the microbiome and the metabolic
      phenotype. We observed a marked shift toward Gammaproteobacteria, particularly
      Enterobacter hormaechei, following Roux-en-Y gastric bypass (RYGB) surgery in a
      rat model compared with sham-operated controls. Fecal water from RYGB surgery
      rats was highly cytotoxic to rodent cells (mouse lymphoma cell line). In
      contrast, fecal water from sham-operated animals showed no/very low cytotoxicity.
      This shift in the gross structure of the microbiome correlated with greatly
      increased cytotoxicity. Urinary phenylacetylglycine and indoxyl sulfate and fecal
      gamma-aminobutyric acid, putrescine, tyramine, and uracil were found to be
      inversely correlated with cell survival rate. This profound co-dependent response
      of mammalian and microbial metabolism to RYGB surgery and the impact on the
      cytotoxicity of the gut luminal environment suggests that RYGB exerts local and
      global metabolic effects which may have an influence on long-term cancer risk and
      cytotoxic load.

PMID- 21949515
TI  - Association of hypomelanotic skin disorders with autism: links to possible
      etiologic role of vitamin-D levels in autism?
AB  - Vitamin D is crucial for several key physiological processes, including brain
      development, DNA repair, and regulation of many genes. Much evidence indicates
      prenatal and early postnatal vitamin-D deficiency increases autism risk, probably
      through multiple effects, including impaired brain development and increased de
      novo mutations. High autism rates in several genetically based hypomelanotic skin
      disorders are puzzling, because ultraviolet-B radiation (UVB) in sunlight acting
      on skin is a key source of vitamin-D, and lighter skin protects against vitamin-D
      deficiency, especially at high latitudes. We consider two hypotheses to help
      explain autism's co-morbidity with hypomelanosis. 1) Because genetic and
      epigenetic variants that produce hypomelanosis help protect against vitamin-D
      deficiency, they increase reproductive fitness of individuals who also have other
      autism risk factors. 2) Hypomelanotic children have increased autism risk because
      photosensitivity and skin-cancer concerns lead families to excessively reduce
      children's sun exposure. Hypothesis testing could involve studies comparing
      genomes, epigenetic markers, skin pigmentation, and vitamin-D levels in autistic
      individuals with and without hypomelanosis, their relatives and controls.
      Conducting such studies in samples from regions that differ widely in UVB
      availability would provide particularly valuable data. Support for either
      hypothesis would elucidate vitamin-D's role in autism and suggest vitamin-D
      enhancement may aid treatment and prevention of autism.

PMID- 21949516
TI  - Excessive crying: behavioral and emotional regulation disorder in infancy.
AB  - In the pediatric literature, excessive crying has been reported solely in
      association with 3-month colic and is described, if at all, as unexplained crying
      and fussing during the first 3 months of life. The bouts of crying are generally
      thought to be triggered by abdominal colic (over-inflation of the still immature
      gastrointestinal tract), and treatment is prescribed accordingly. According to
      this line of reasoning, excessive crying is harmless and resolves by the end of
      the third month without long-term consequences. However, there is evidence that
      it may cause tremendous distress in the mother-infant relationship, and can lead
      to disorders of behavioral and emotional regulation at the toddler stage (such as
      sleep and feeding disorders, chronic fussiness, excessive clinginess, and temper
      tantrums). Early treatment of excessive crying focuses on parent-infant
      communication, and parent-infant interaction in the context of soothing and
      settling the infant to sleep is a promising approach that may prevent later
      behavioral and emotional disorders in infancy.

PMID- 21949517
TI  - Acute disseminated encephalomyelitis in children: differential diagnosis from
      multiple sclerosis on the basis of clinical course.
AB  - Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease of the
      central nervous system (CNS) that typically presents as a monophasic disorder
      associated with multifocal neurologic symptoms and encephalopathy. ADEM is
      considered an autoimmune disorder that is triggered by an environmental stimulus
      in genetically susceptible individuals. The diagnosis of ADEM is based on
      clinical and radiological features. Most children with ADEM initially present
      with fever, meningeal signs, and acute encephalopathy. The level of consciousness
      ranges from lethargy to frank coma. Deep and subcortical white-matter lesions and
      gray-matter lesions such as thalami and basal ganglia on magnetic resonance
      imaging (MRI) are associated with ADEM. In a child who presents with signs of
      encephalitis, bacterial and viral meningitis or encephalitis must be ruled out.
      Sequential MRI is required to confirm the diagnosis of ADEM, as relapses with the
      appearance of new lesions on MRI may suggest either multiphasic ADEM or multiple
      sclerosis (MS). Pediatric MS, defined as onset of MS before the age of 16, is
      being increasingly recognized. MS is characterized by recurrent episodes of
      demyelination in the CNS separated in space and time. The McDonald criteria for
      diagnosis of MS include evidence from MRI and allow the clinician to make a
      diagnosis of clinically definite MS on the basis of the interval preceding the
      development of new white matter lesions, even in the absence of new clinical
      findings. The most important alternative diagnosis to MS is ADEM. At the initial
      presentation, the 2 disorders cannot be distinguished with certainty. Therefore,
      prolonged follow-up is needed to establish a diagnosis.

PMID- 21949518
TI  - Mammalian target of rapamycin inhibitors for treatment in tuberous sclerosis.
AB  - Tuberous sclerosis complex (TSC) is a genetic multisystem disorder that results
      from mutations in the TSC1 or TSC2 genes, and is associated with hamartomas in
      several organs, including subependymal giant cell tumors. The neurological
      manifestations of TSC are particularly challenging and include infantile spasms,
      intractable epilepsy, cognitive disabilities, and autism. The TSC1- and TSC2
      encoded proteins modulate cell function via the mammalian target of rapamycin
      (mTOR) signaling cascade, and are key factors in the regulation of cell growth
      and proliferation. The mTOR pathway provides an intersection for an intricate
      network of protein cascades that respond to cellular nutrition, energy levels,
      and growth factor stimulation. In the brain, TSC1 and TSC2 have been implicated
      in cell body size, dendritic arborization, axonal outgrowth and targeting,
      neuronal migration, cortical lamination, and spine formation. The mTOR pathway
      represents a logical candidate for drug targeting, because mTOR regulates
      multiple cellular functions that may contribute to epileptogenesis, including
      protein synthesis, cell growth and proliferation, and synaptic plasticity.
      Antagonism of the mTOR pathway with rapamycin and related compounds may provide
      new therapeutic options for TSC patients.

PMID- 21949519
TI  - Outcomes of small for gestational age micropremies depending on how young or how
      small they are.
AB  - PURPOSE: The outcomes of small for gestational age (SGA) infants especially in
      extremely low birth weight infants (ELBWIs) are controversial. This study
      evaluated the mortality and morbidity of ELBWIs, focusing on whether or not they
      were also SGA. METHODS: The medical records of 415 ELBWIs (birth weight <1,000
      g), who were inborn and admitted to the Samsung Medical Center neonatal intensive
      care unit from January 2000 to December 2008, were reviewed retrospectively.
      Mortality and morbidities were compared by body size groups: very SGA (VSGA),
      birth weight <=3rd percentile; SGA, 3rd to 10th percentile; and appropriate for
      gestational age (AGA) infants, >10th percentile for gestational age. For
      gestational subgroup analysis, groups were divided into infants with gestational
      age <=24(+6) weeks (subgroup I), 25(+0) to 26(+6) weeks (subgroup II), and
      >=27(+0) weeks (subgroup III). RESULTS: Gestational age was 29(+2)+/-2(+6) weeks
      in the VSGA infants (n=49), 27(+5)+/-2(+2) weeks in the SGA infants (n=45), and
      25(+4)+/-1(+4) weeks in AGA infants (n=321). Birth weight was 692+/-186.6 g,
      768+/-132.9 g, and 780+/-142.5 g in the VSGA, SGA, and AGA groups, respectively.
      Cesarean section rate and maternal pregnancy-induced hypertension were more
      common in the VSGA and SGA than in AGA pregnancies. However, chorioamnionitis was
      more common in the AGA group. The mortalities of the lowest gestational group
      (subgroup I), and also of the lower gestational group (subgroup I+II) were
      significantly higher in the VSGA group than the SGA or AGA groups (P=0.020 and
      P=0.012, respectively). VSGA and SGA infants showed lower incidence in
      respiratory distress syndrome, ductal ligation, bronchopulmonary dysplasia,
      intraventricular hemorrhage than AGA group did. However, by multiple logistic
      regression analysis of each gestational subgroup, the differences were not
      significant. CONCLUSION: Of ELBWIs, extremely SGA in the lower gestational
      subgroups, had an impact on mortality, which may provide information useful for
      prenatal counseling.

PMID- 21949520
TI  - The metabolic syndrome and body composition in childhood cancer survivors.
AB  - PURPOSE: Long-term survivors of childhood cancer appear to have an increased risk
      for the metabolic syndrome, subsequent type 2 diabetes and cardiovascular disease
      in adulthood compared to healthy children. The purpose of this study was to
      investigate the frequency of the metabolic syndrome and associated factors in
      childhood cancer survivors at a single center in Korea. METHODS: We performed a
      retrospective review of medical records of 98 childhood cancer survivors who were
      diagnosed and completed anticancer treatment at Samsung Medical Center, Seoul,
      Korea between Jan. 1996 and Dec. 2007. Parameters of metabolic syndrome were
      evaluated between Jan. 2008 and Dec. 2009. Clinical and biochemical findings
      including body fat percentage were analyzed. RESULTS: A total of 19 (19.4%)
      patients had the metabolic syndrome. The median body fat percentage was 31.5%.
      The body mass index and waist circumference were positively correlated with the
      cranial irradiation dose (r=0.38, P<0.001 and r=0.44, P<0.00, respectively).
      Sixty-one (62.2%) patients had at least one abnormal lipid value. The
      triglyceride showed significant positive correlation with the body fat percentage
      (r=0.26, P=0.03). The high density lipoprotein cholesterol showed significant
      negative correlation with the percent body fat (r=-0.26, P=0.03). CONCLUSION:
      Childhood cancer survivors should have thorough metabolic evaluation including
      measurement of body fat percentage even if they are not obese. A better
      understanding of the determinants of the metabolic syndrome during adolescence
      might provide preventive interventions for improving health outcomes in
      adulthood.

PMID- 21949521
TI  - Clinical features of infantile hepatic hemangioendothelioma.
AB  - PURPOSE: Infantile hepatic hemangioendothelioma (IHHE) is the most common type of
      hepatic vascular tumor in infancy. We conducted this study to review our clinical
      experience of patients with IHHE and to suggest management strategies. METHODS:
      We retrospectively analyzed the medical records of 23 IHHE patients (10 males, 13
      females) treated at the Asan Medical Center between 1996 and 2009. RESULTS:
      Median age at diagnosis was 38 days (range, 1 to 381 days). Seven patients (30%)
      were diagnosed with IHHE based on sonographically detected fetal liver masses, 5
      (22%) were diagnosed incidentally in the absence of symptoms, 5 (22%) had
      congestive heart failure, 3 (13%) had skin hemangiomas, 2 (9%) had abnormal liver
      function tests, and 1 (4%) had hepatomegaly. All diagnoses were based on imaging
      results, and were confirmed in three patients by histopathology analysis. Six
      patients were observed without receiving any treatment, whereas 12 received
      corticosteroids and/or interferon-alpha. One patient with congestive heart
      failure and a resectable unilobar tumor underwent surgical resection. Three
      patients with congestive heart failure and unresectable tumors were managed by
      hepatic artery embolization with/without medical treatment. At a median follow-up
      of 29 months (range, 1 to 156 months), 21 (91%) patients showed complete tumor
      disappearance or >50% decrease in tumor size. One patient died due to tumor
      related causes. CONCLUSION: IHHE generally has a benign clinical course with low
      morbidity and mortality rates. Clinical course and treatment outcome did not
      differ significantly between medically treated and non-treated groups. Surgically
      unresectable patients with significant symptoms may be treated medically or with
      hepatic artery embolization.

PMID- 21949522
TI  - A case of de novo duplication of 15q24-q26.3.
AB  - Distal duplication, or trisomy 15q, is an extremely rare chromosomal disorder
      characterized by prenatal and postnatal overgrowth, mental retardation, and
      craniofacial malformations. Additional abnormalities typically include an
      unusually short neck, malformations of the fingers and toes, scoliosis and
      skeletal malformations, genital abnormalities, particularly in affected males,
      and, in some cases, cardiac defects. The range and severity of symptoms and
      physical findings may vary from case to case, depending upon the length and
      location of the duplicated portion of chromosome 15q. Most reported cases of
      duplication of the long arm of chromosome 15 frequently have more than one
      segmental imbalance resulting from unbalanced translocations involving chromosome
      15 and deletions in another chromosome, as well as other structural chromosomal
      abnormalities. We report a female newborn with a de novo duplication, 15q24
      q26.3, showing intrauterine overgrowth, a narrow asymmetric face with down
      slanting palpebral fissures, a large, prominent nose, and micrognathia,
      arachnodactyly, camptodactyly, congenital heart disease, hydronephrosis, and
      hydroureter. Chromosomal analysis showed a
      46,XX,inv(9)(p12q13),dup(15)(q24q26.3). Array comparative genomic hybridization
      analysis revealed a gain of 42 clones on 15q24-q26.3. This case represents the
      only reported patient with a de novo 15q24-q26.3 duplication that did not result
      from an unbalanced translocation and did not have a concomitant monosomic
      component in Korea.

PMID- 21949523
TI  - A sporadic case of Loeys-Dietz syndrome type I with two novel mutations of the
      TGFBR2 gene.
AB  - A recently recognized connective tissue disorder, Loeys-Dietz syndrome (LDS) is a
      genetic aortic aneurysm syndrome caused by mutations in the transforming growth
      factor-receptor type I or II gene (TGFBR1 or TGFBR2). They have distinctive
      phenotypic abnormalities including widely spaced eyes (hypertelorism), bifid
      uvula or cleft palate, and arterial tortuosity with aortic aneurysm or dissection
      throughout the arterial tree. LDS is characterized by aggressive and rapid
      progression of aortic aneurysm. Therefore, the patients with distinct phenotype,
      marked aortic dilatation and aneurysm at early age should be suspected to be
      affected by LDS and rapid TGFBR gene analysis should be done. We report one child
      diagnosed as LDS due to typical phenotypes and two novel missense mutations of
      the TGFBR2 gene (c.1526G>T and c.1528A>T).

PMID- 21949524
TI  - Computational fluid dynamics in cardiovascular disease.
AB  - Computational fluid dynamics (CFD) is a mechanical engineering field for
      analyzing fluid flow, heat transfer, and associated phenomena, using computer
      based simulation. CFD is a widely adopted methodology for solving complex
      problems in many modern engineering fields. The merit of CFD is developing new
      and improved devices and system designs, and optimization is conducted on
      existing equipment through computational simulations, resulting in enhanced
      efficiency and lower operating costs. However, in the biomedical field, CFD is
      still emerging. The main reason why CFD in the biomedical field has lagged behind
      is the tremendous complexity of human body fluid behavior. Recently, CFD
      biomedical research is more accessible, because high performance hardware and
      software are easily available with advances in computer science. All CFD
      processes contain three main components to provide useful information, such as
      pre-processing, solving mathematical equations, and post-processing. Initial
      accurate geometric modeling and boundary conditions are essential to achieve
      adequate results. Medical imaging, such as ultrasound imaging, computed
      tomography, and magnetic resonance imaging can be used for modeling, and Doppler
      ultrasound, pressure wire, and non-invasive pressure measurements are used for
      flow velocity and pressure as a boundary condition. Many simulations and clinical
      results have been used to study congenital heart disease, heart failure,
      ventricle function, aortic disease, and carotid and intra-cranial cerebrovascular
      diseases. With decreasing hardware costs and rapid computing times, researchers
      and medical scientists may increasingly use this reliable CFD tool to deliver
      accurate results. A realistic, multidisciplinary approach is essential to
      accomplish these tasks. Indefinite collaborations between mechanical engineers
      and clinical and medical scientists are essential. CFD may be an important
      methodology to understand the pathophysiology of the development and progression
      of disease and for establishing and creating treatment modalities in the
      cardiovascular field.

PMID- 21949525
TI  - Large circular ring catheter ablation versus anatomically guided ablation of
      atrial fibrillation: back to the future for successful catheter ablation of
      atrial fibrillation?

PMID- 21949526
TI  - Comparison of recurrence rate based on the frequency of preceding symptoms in
      patients with neurocardiogenic syncope or presyncope.
AB  - BACKGROUND AND OBJECTIVES: In patients with neurocardiogenic syncope or
      presyncope, symptoms developed unpredictably and intermittently. The purpose of
      this study was to determine whether there was any significant difference in the
      recurrence rate of symptoms during the follow-up period between patients with
      many episodes of symptoms and those with fewer episodes of symptoms before
      diagnosis, as well as to assess the clinical significance of previous episodes of
      symptoms during treatment. SUBJECTS AND METHODS: A total of 100 patients with
      neurocardiogenic syncope or presyncope were divided in two groups (high episode
      group, n=54; low episode group, n=46) according to the frequency of symptoms
      before the head-up tilt test. We retrospectively analyzed the recurrence of
      symptoms using telephone interviews and medical record reviews. RESULTS: The
      clinical characteristics were not significantly different between the two groups.
      However, the recurrence rate was significantly lower in the high episode group
      than in the low episode group (5.6% vs. 19.6%, p=0.001). In the high episode
      group, patients treated with medication showed higher recurrence of symptoms than
      those without medication. In the lower episode group, a similar result was
      observed. CONCLUSION: The frequency of previous symptoms at the diagnosis of
      neurocardiogenic syncope or presyncope did not predict the occurrence of symptoms
      during the follow-up period. Therefore, to continue drug treatment based on the
      frequency of symptoms in patients with neurocardiogenic syncope or presyncope may
      not be the best option.

PMID- 21949527
TI  - Relation between high-sensitivity C-reactive protein and coronary plaque
      components in patients with acute coronary syndrome: virtual histology
      intravascular ultrasound analysis.
AB  - BACKGROUND AND OBJECTIVES: We used virtual histology-intravascular ultrasound (VH
      IVUS) to evaluate the relationship between high-sensitivity C-reactive protein
      (hs-CRP) levels and plaque components in 279 acute coronary syndrome (ACS)
      patients. SUBJECTS AND METHODS: We divided patients into three groups according
      to their hs-CRP levels {lowest tertile <0.07 mg/dL (n=93), middle tertile >=0.07,
      <0.4 mg/dL (n=93), and highest tertile >=0.4 mg/dL (n=93)}. Thin-cap
      fibroatheroma (TCFA) was defined as focal, necrotic core (NC)-rich (>=10% of the
      cross-sectional area) plaques in contact with the lumen in a plaque burden >=40%.
      RESULTS: The highest tertile group was mostly diabetics (20%, 27%, 40%, p=0.009),
      and had the greatest plaque plus media volume (163+/-139/mm(3) vs. 201+/
      155/mm(3) vs. 232+/-176/mm(3), p=0.013). The highest tertile group had the
      greatest absolute and % NC volumes (13.6+/-15.1 mm(3) vs. 14.8+/-14.2 mm(3) vs.
      23.7+/-24.3 mm(3), p<0.001, and 14.9+/-8.7% vs. 16.0+/-8.7% vs. 19.5+/-10.2%,
      p=0.024, respectively). The culprit lesion TCFA was observed most frequently in
      the highest tertile group (28% vs. 35% vs. 55%, p=0.006). By multivariable
      analysis, absolute NC volume was an independent predictor of hs-CRP elevation
      {odds ratio (OR); 1.03, 95% confidence interval (CI)=1.06-1.21, p=0.004}, and hs
      CRP was an independent predictor of TCFA (OR; 1.86, 95% CI=1.11-2.90, p=0.010).
      CONCLUSION: VH-IVUS analysis has demonstrated that ACS patients with elevated hs
      CRP have more vulnerable plaque component (NC-rich plaques and higher frequency
      of culprit lesion TCFA), compared with ACS patients with normal hs-CRP.

PMID- 21949528
TI  - The feasibility and efficacy of a large-sized lasso catheter combined with 3
      dimensional mapping system for catheter ablation of atrial fibrillation.
AB  - BACKGROUND AND OBJECTIVES: We aimed to investigate whether a large-sized Lasso
      catheter could increase the success rate of immediate complete pulmonary vein
      (PV) antral isolation and improve the outcome of catheter ablation in atrial
      fibrillation (AF) patients. SUBJECTS AND METHODS: This study included 107
      consecutive patients (67 males, mean age: 57.8+/-9.7 years) who underwent PV
      mapping and ablation due to symptomatic drug-refractory AF. The first 43 patients
      underwent isolation of both ipsilateral PVs using the Carto-Merge 3 dimensional
      mapping system (group 1). The other 64 patients underwent isolation of both
      ipsilateral PVs using the same technique with a large-sized (a diameter of 30 to
      35 mm) Lasso cathe-ter (group 2). When ipsilateral PVs did not show any potential
      after the initial circumferential ablation, we defined this as 'immediate
      complete antral isolation (ICAI)'. We compared the AF recurrence rate of both
      groups. RESULTS: There was no significant difference of the clinical
      characteristics between group 1 and group 2. All the patients were followed-up
      for 1 year. The ICAI rate of group 1 and group 2 was significantly different (21%
      vs. 78%, p<0.001), and the AF recurrence rates of group 1 and group 2 were also
      different (34.9% vs. 18.8%, p=0.042). Using multiple logistic regression
      analysis, the use of a large-sized Lasso catheter was a significant predictive
      factor for preventing recurrence (odds ratio: 0.489, 95% confidence interval:
      0.136-0.927). CONCLUSION: It is likely that a large-sized Lasso catheter plays an
      important role in achieving ICAI and in lowering the rate of AF recurrence.

PMID- 21949529
TI  - Thrombophilia, left ventricular dysfunction and intracardiac thrombi in children.
AB  - BACKGROUND AND OBJECTIVES: Reports on the incidence of intracardiac thrombi (ICT)
      have increased over the last few decades, but ICT are still relatively rare among
      children. Left ventricular systolic dysfunction and dilatation may contribute to
      the formation of ICT, especially when a hypercoagulable state exists. The aim of
      this study was to describe the incidence of ICT in children suffering from
      cardiac failure with left ventricular dysfunction and to identify risk factors on
      admission for developing ICT. SUBJECTS AND METHODS: We conducted a retrospective
      chart review of children up to 18 years of age admitted to the Pediatric
      Intensive Care Unit due to cardiac failure with left ventricular dysfunction
      between January 1, 2003 and December 31, 2008. RESULTS: Twenty-one patients were
      admitted with clinical signs of cardiac failure and echocardiographic findings
      compatible with dilated cardiomyopathy or acute myocarditis. Dilated
      cardiomyopathy was diagnosed in 11 patients (52%). Adenoviruses and enteroviruses
      were suspected to be the cause of acute myocarditis in 5 cases. The personal or
      family history of hypercoagulable states were obtained from 19 out of 21 patients
      (90%). Among patients with a hypercoagulable state, 3 out of 7 developed ICT
      compared with none out of 12 among patients without hypercoagulability (p=0.043).
      Two of these 3 patients experienced an embolic event. CONCLUSION: Cardiac failure
      with left ventricular dysfunction may predispose the patient to ICT and increase
      the risk of thromboembolism, especially when an underlying hypercoagulable state
      exists. The hypercoagulable state must be carefully evaluated on admission in
      these patients.

PMID- 21949530
TI  - Effect of previous statin therapy in patients with acute coronary syndrome and
      percutaneous coronary intervention.
AB  - BACKGROUND AND OBJECTIVES: Statin therapy after percutaneous coronary
      intervention (PCI) has been associated with reduced major adverse cardiovascular
      events (MACE). However, it has been less clear as to whether statin therapy
      before acute coronary syndrome (ACS) is beneficial. We studied the effect of
      previous statin therapy, initiated >=1 month before PCI, on the outcome of
      patients with ACS who had undergone early invasive strategies. SUBJECTS AND
      METHODS: We stratified 479 consecutive patients with ACS who had undergone PCI,
      according to preprocedural statin administration as follows: previous statin
      treated patients (statin group, n=237) and statin-naive patients (control group,
      n=242). The incidence of periprocedural myocardial infarction (MI) and in
      hospital MACE was assessed. RESULTS: The incidence of Braunwald class III angina
      and MI presentation were significantly lower in the statin group than in the
      control group. Angiographic and procedural characteristics were similar between
      the two groups; however, slow/no reflow phenomenon occurred more frequently in
      the control group. After PCI, the incidence of periprocedural MI was higher in
      the control group than in the statin group (6.6% vs. 2.1%, p=0.016). Multivariate
      analysis revealed that no prior use of statin {odds ratio (OR)=2.8; 95%
      confidence interval (CI)=1.1-7.2; p=0.038), procedural complication (OR=4.0; 95%
      CI=1.5-10.5; p=0.004), stent overlap (OR=4.7; 95% CI=1.3-16.4; p=0.015), and old
      age (OR=3.2; 95% CI=1.2-8.0; p=0.016) were independent predictors for in-hospital
      MACE. CONCLUSION: Previous statin therapy before ACS was associated with milder
      clinical presentation and lower incidence of in-hospital MACE after early
      invasive strategies. The beneficial outcome is attributable to a significant
      reduction in periprocedural MI after PCI.

PMID- 21949531
TI  - Aneurysm of sinus of valsalva dissecting into the interventricular septum after
      aortic valve replacement: diagnosis by echocardiography and magnetic resonance
      imaging and treatment with surgical sealant.
AB  - Aneurysm of the sinus of Valsalva that causes dissection of the interventricular
      septum is an extremely rare entity. In this report we describe a case of aneurysm
      of the sinus of Valsalva dissecting into the interventricular septum, from the
      base to mid septum, after aortic valve replacement. After the diagnosis was made
      by transthoracic echocardiography and magnetic resonance imaging, the patient was
      successfully treated with surgical sealant-mediated occlusion of the aneurysmal
      sac and cardiac resynchronization therapy used for the first time.

PMID- 21949532
TI  - Successful treatment of a ruptured aortic arch aneurysm using a hybrid procedure.
AB  - Aortic rupture has a high mortality rate and can be considered a medical
      emergency. The standard treatment for aortic rupture is surgical repair. An
      aortic stent graft for a ruptured descending aorta is considered an effective
      alternative treatment. However, an aortic stent graft is difficult when the
      aortic aneurysm is in the aortic arch due to supra-aortic vessels. We report on a
      patient with a ruptured aortic arch aneurysm treated with a hybrid procedure,
      which involved a carotid to carotid bypass operation and an aortic stent graft. A
      71-year-old male patient visited our cardiovascular center suffering from
      hemoptysis. The chest CT and aortography showed a 9 cm sized aortic arch aneurysm
      0.5 cm distal to the left subclavian artery and a hemothorax in the left lung.
      The patient refused to undergo a full open operation. We performed a carotid to
      carotid bypass in advance, and two pieces of aortic stent grafts were placed
      across the left carotid artery and left subclavian artery. The follow up CT
      showed the aortic stent grafts, no endoleaks and no thrombus in the aortic arch
      aneurysm. The patient was discharged from the hospital without complication.

PMID- 21949533
TI  - Is a metallic microcoil really a permanent embolic agent for the management of
      distal guidewire-induced coronary artery perforation?
AB  - Coronary artery perforation (CAP) after percutaneous coronary intervention is a
      rare, but serious complication. It can cause cardiac tamponade, acute myocardial
      infarction or death. The treatments of CAP involve prolonged balloon inflation,
      emergent surgery, coil embolization, and implantation of covered stent. We have
      successfully performed the emergent microcoil embolization in a patient with
      uncontrolled Ellis grade 3 guidewire-induced CAP resulting in delayed cardiac
      tamponade. Contrasting our usual expectation, the 1-year follow-up angiography
      showed a patent flow at the embolized site.

PMID- 21949534
TI  - Tako-tsubo cardiomyopathy triggered by misdirection.
AB  - Tako-Tsubo cardiomyopathy (TTC), also known as transient left ventricular apical
      ballooning syndrome or stress-induced cardiomyopathy, is a novel reversible
      cardiomyopathy mimicking acute myocardial infarction without epicardial coronary
      artery disease. The exact physiopathology of TTC remains unclear. It is usually
      precipitated by acute physical or emotional stress and it most commonly affects
      postmenopausal women. The growing number of clinical cases of TTC have
      demonstrated a wide field of possible etiologies beyond the emotional stress. We
      report a case of a 67-year-old postmenopausal woman who was being supplemented by
      enteral feeding via a nasogastric tube and who developed TTC due to misdirection,
      probably favored by the mechanical blockade by the nasogastric tube, while
      swallowing the drug pills.

PMID- 21949535
TI  - A case of staphylococcal tricuspid valve endocarditis with para-aortic abscess in
      a patient with bicuspid aortic valve.
AB  - Paravalvular abscess is a serious complication of infective endocarditis. The
      aortic valve and its adjacent ring are more susceptible to abscess formation and
      paravalvular extension than the mitral valve. A 15-years old patient with
      bicuspid aortic valve presented with staphylococcal tricuspid valve endocarditis
      complicated by para-aortic abscess that ruptured into the aortic sinus. We report
      the clinical, laboratory and echocardiographic features and treatment of this
      patient and conduct a literature review on this subject.

PMID- 21949536
TI  - A Case of Distal Embolization of Left Ventricular Thrombus due to Blunt Chest
      Trauma-Induced Coronary Artery Occlusion.
AB  - Chest trauma can lead to various cardiac complications ranging from simple
      arrhythmias to myocardial rupture. A variety of injuries to the coronary
      arteries, including laceration, thrombosis, intimal dissection, arteriovenous
      fistula and pseudoaneurysm formation following blunt trauma have been rarely
      reported. We report a very unusual case of distal embolization of left
      ventricular thrombus due to blunt chest trauma-induced coronary artery occlusion.

PMID- 21949537
TI  - Hemorrhagic transformation of ischemic stroke: severe complications of prosthetic
      valve endocarditis.
AB  - Ischemic stroke is a common complication of infective endocarditis (IE),
      occurring in 20-40% of left side IE cases. In these subsets, anticoagulation
      therapy may provoke hemorrhagic transformation (HT) of ischemic stroke, and
      complications of this magnitude deteriorate the clinical course for IE patients.
      However, in cases of IE complicated with a mechanical prosthetic valve, the
      physician can be concerned over the maintenance of anticoagulation due to the
      risk of thrombotic complication. According to our retrospective review, HT of
      ischemic stroke in prosthetic valve endocarditis occurred 13.8% (4/29) of the
      time in a variety of situations. Some of these even arose in patients with a
      subtherapeutic range of prothrombin time.

PMID- 21949538
TI  - Modified damus-kaye-stansel/dor procedure for a newborn with severe left
      ventricular aneurysm.
AB  - Congenital left ventricular aneurysm (CVA) is a rare cardiac malformation. The
      prognosis is variable, depending on such factors as the size in comparison to the
      ventricular cavity, signs of heart failure, arrhythmia and so on. Most infants
      and young children with large aneurysm showed poor clinical outcomes. Here, we
      report the case of patient who was prenatally diagnosed with a large CVA, who had
      severe left ventricular dysfunction at 21 weeks' gestation for which she
      successfully underwent a modified Damus-Kaye-Stansel/Dor procedure.

PMID- 21949539
TI  - Mistreating Psychology in the Decades of the Brain.
AB  - We systematically mistreat psychological phenomena, both logically and
      clinically. This article explores three contentions: that the dominant discourse
      in modern cognitive, affective, and clinical neuroscience assumes that we know
      how psychology/biology causation works when we do not; that there are serious
      intellectual, clinical, and policy costs to pretending we do know; and that
      crucial scientific and clinical progress will be stymied as long as we frame
      psychology, biology, and their relationship in currently dominant ways. The
      arguments are developed with emphasis on misguided attempts to localize
      psychological function via neuroimaging, misunderstandings about the role of
      genetics in psychopathology, and untoward constraints on health-care policy and
      clinical service delivery. A particular challenge, articulated but not resolved
      in this article, is determining what constitutes adequate explanation in the
      relationship between psychology and biology. 

PMID- 21949541
TI  - ADAPTIVE FINITE ELEMENT MODELING TECHNIQUES FOR THE POISSON-BOLTZMANN EQUATION.
AB  - We consider the design of an effective and reliable adaptive finite element
      method (AFEM) for the nonlinear Poisson-Boltzmann equation (PBE). We first
      examine the two-term regularization technique for the continuous problem recently
      proposed by Chen, Holst, and Xu based on the removal of the singular
      electrostatic potential inside biomolecules; this technique made possible the
      development of the first complete solution and approximation theory for the
      Poisson-Boltzmann equation, the first provably convergent discretization, and
      also allowed for the development of a provably convergent AFEM. However, in
      practical implementation, this two-term regularization exhibits numerical
      instability. Therefore, we examine a variation of this regularization technique
      which can be shown to be less susceptible to such instability. We establish a
      priori estimates and other basic results for the continuous regularized problem,
      as well as for Galerkin finite element approximations. We show that the new
      approach produces regularized continuous and discrete problems with the same
      mathematical advantages of the original regularization. We then design an AFEM
      scheme for the new regularized problem, and show that the resulting AFEM scheme
      is accurate and reliable, by proving a contraction result for the error. This
      result, which is one of the first results of this type for nonlinear elliptic
      problems, is based on using continuous and discrete a priori L(infinity)
      estimates to establish quasi-orthogonality. To provide a high-quality geometric
      model as input to the AFEM algorithm, we also describe a class of feature
      preserving adaptive mesh generation algorithms designed specifically for
      constructing meshes of biomolecular structures, based on the intrinsic local
      structure tensor of the molecular surface. All of the algorithms described in the
      article are implemented in the Finite Element Toolkit (FETK), developed and
      maintained at UCSD. The stability advantages of the new regularization scheme are
      demonstrated with FETK through comparisons with the original regularization
      approach for a model problem. The convergence and accuracy of the overall AFEM
      algorithm is also illustrated by numerical approximation of electrostatic
      solvation energy for an insulin protein.

PMID- 21949542
TI  - Diagnosis and treatment of developmental dysplasia of the hip in the Netherlands:
      national questionnaire of paediatric orthopaedic surgeons on current practice in
      children less than 1 year old.
AB  - PURPOSE: There is no consensus in the literature regarding the diagnosis and
      treatment of developmental dysplasia of the hip (DDH). We designed a national
      questionnaire to assess the various opinions and current practice of paediatric
      orthopaedic surgeons in the Netherlands regarding the diagnosis and treatment of
      DDH in children less than 1 year old.  METHODS: The questionnaire was sent to all
      members of the Dutch Paediatric Orthopaedic Society (DPOS). It discusses
      different methods and criteria used in the diagnosis of DDH, the use of different
      therapies and the use of different imaging techniques to evaluate the result of
      treatment.  RESULTS: With 38 responders, the overall response rate to the survey
      was 67%. Most surgeons use clinical, radiographic and/or ultrasound examination
      for the diagnosis. The starting point of treatment is usually on the mild part of
      the DDH spectrum. The Pavlik harness is most popular in the treatment of
      dislocated hips, whereas in dysplastic hips, most surgeons use a rigid splint.
      The duration of treatment has a wide range and evaluation of the effect of
      treatment is predominantly done by radiography.  CONCLUSIONS: The diagnosis and
      treatment of DDH in the Netherlands has as much diversity as the literature has
      recommendations about this subject. The lack of consensus on many aspects of DDH
      diagnosis and treatment should form the basis for a discussion among Dutch
      paediatric orthopaedic surgeons. Using the available evidence, it should be
      possible to formulate a more uniform protocol for the diagnosis and treatment of
      DDH.

PMID- 21949540
TI  - The Utility of Animal Models in Understanding Links between Psychosocial
      Processes and Cardiovascular Health.
AB  - A bidirectional association between mood disorders and cardiovascular disease has
      been described; however, the neurobiological mechanisms that underlie this link
      have not been fully elucidated. The purpose of this review is first to describe
      some of the important behavioral neurobiological processes that are common to
      both mood and cardiovascular disorders. Second, this review focuses on the value
      of conducting research with animal models (primarily rodents) to investigate
      potential behavioral, physiological, and neural processes involved in the
      association of mood disorders and cardiovascular disease. In combination with
      findings from human research, the study of mechanisms underlying mood and
      cardiovascular regulation using animal models will enhance our understanding of
      the association of depression and cardiovascular disease, and can promote the
      development of novel interventions for individuals with these comorbid
      conditions.

PMID- 21949543
TI  - The value of clinical examination in diagnosing pelvic fractures in blunt trauma
      patients: a brief review.
AB  - PURPOSE OF THE STUDY: To evaluate the value of a pelvic X-ray compared to
      clinical examination in diagnosing pelvic ring fractures, using computed
      tomography (CT) as the gold standard, in alert [Glasgow Coma Scale (GCS) >= 13]
      adult blunt trauma patients in the emergency room. METHODS: A systematic
      literature search was performed in PubMed and Embase. The results were screened
      on their titles and abstracts using in- and exclusion criteria. Subsequently, the
      selected articles were critically appraised for their relevance and validity.
      RESULTS: Two studies investigating the diagnostic value of clinical examination
      and pelvic X-ray compared to CT were identified. Both studies demonstrate higher
      negative predictive values for clinical examination [0.99 (95% confidence
      interval [CI] 0.98-1.0) and 1.0 (95% CI 0.99-1.0)] compared to the negative
      predictive values of pelvic X-ray [0.98 (95% CI 0.93-0.99) and 0.99 (95% CI 0.99
      1.0)]. The positive predictive values for clinical examination were low [0.18
      (95% CI 0.16-0.23) and 0.35 (95% CI 0.30-0.42)] compared to pelvic X-ray [0.97
      (95% CI 0.96-0.98) and 0.97 (95% CI 0.90-0.99)]. CONCLUSIONS: In alert blunt
      trauma patients, pelvic X-ray only has additional diagnostic value for the
      detection of pelvic ring fractures if the clinical examination is positive.
      Pelvic X-ray should not be performed if the clinical examination is negative. In
      this manner, the expenditure of time, costs, and radiation are optimized.

PMID- 21949544
TI  - Elucidation of the Molecular Mechanisms of Action of the Natural Antimicrobial
      Peptide Subtilosin Against the Bacterial Vaginosis-associated Pathogen
      Gardnerella vaginalis.
AB  - Subtilosin A is a 35-amino acid long cyclical peptide produced by Bacillus
      amyloliquefaciens that has potent antimicrobial activity against a variety of
      human pathogens, including the bacterial vaginosis-related Gardnerella vaginalis.
      The specific mode of action of subtilosin against G. vaginalis was elucidated by
      studying its effects on the proton motive force's (PMF) components: transmembrane
      electric potential (DeltaPsi), transmembrane pH gradient (DeltapH), and
      intracellular ATP levels. The addition of subtilosin to G. vaginalis cells caused
      an immediate and total depletion of the DeltapH, but had no effect on the
      DeltaPsi. Subtilosin also triggered an instant but partial efflux of
      intracellular ATP that was twofold higher than that of the positive control
      bacteriocin, nisin. Taken together, these data suggest that subtilosin inhibits
      G. vaginalis growth by creating transient pores in the cells' cytoplasmic
      membrane, leading to an efflux of intracellular ions and ATP and eventually cell
      death.

PMID- 21949545
TI  - A short history of the first 3 years of the Community Genetics Network and its
      newsletter.
AB  - When in 2007 it became clear that the Karger journal Community Genetics would
      change its name and scope, the first author started to establish an
      international, multidisciplinary e-mail network and a newsletter with papers
      authored by the members of the network. This paper reports on the first 3 years
      of the network. At the end of the 3-year period, there were 858 members, 50
      newsletters had appeared, and almost 1,500 different papers from 458 journals had
      been cited. This model may serve as an example for others who want to bring
      together those sharing a common interest.

PMID- 21949546
TI  - Epigenetic regulation of S100 protein expression.
AB  - S100 proteins are small, calcium-binding proteins whose genes are localized in a
      cluster on human chromosome 1. Through their ability to interact with various
      protein partners in a calcium-dependent manner, the S100 proteins exert their
      influence on many vital cellular processes such as cell cycle, cytoskeleton
      activity and cell motility, differentiation, etc. The characteristic feature of
      S100 proteins is their cell-specific expression, which is frequently up- or
      downregulated in various pathological states, including cancer. Changes in S100
      protein expression are usually characteristic for a given type of cancer and are
      therefore often considered as markers of a malignant state. Recent results
      indicate that changes in S100 protein expression may depend on the extent of DNA
      methylation in the S100 gene regulatory regions. The range of epigenetic changes
      occurring within the S100 gene cluster has not been defined. This article reviews
      published data on the involvement of epigenetic factors in the control of S100
      protein expression in development and cancer.

PMID- 21949548
TI  - The role of epigenetic dysregulation in the epidemic of allergic disease.
AB  - The epidemic of allergic disease in early life is one of the clearest indicators
      that the developing immune system is vulnerable to modern environmental changes.
      A range of environmental exposures epidemiologically associated with allergic
      disease have been shown to have effects on the foetal immune function in
      pregnancy, including microbial burden, dietary changes and environmental
      pollutants. Preliminary studies now suggest that these early effects on immune
      development may be mediated epigenetically through a variety of processes that
      collectively modify gene expression and allergic susceptibility and that these
      effects are potentially heritable across generations. It is also possible that
      rising rates of maternal allergy, a recognised direct risk factor for infant
      allergic disease, may be further amplifying the effects of environmental changes.
      Whilst effective prevention strategies are the ultimate goal in reversing the
      allergy epidemic, the specific environmental drivers, target genes, and
      intracellular pathways and mechanisms of early life immune programming are still
      unclear. It is hoped that identifying genes that are differentially regulated in
      association with subsequent allergic disease will assist in identifying causal
      pathways and upstream contributing environmental factors. In this way, epigenetic
      paradigms are likely to provide valuable insights into how the early environment
      can be modified to more favourably drive immune development and reverse the
      allergic epidemic.

PMID- 21949547
TI  - MicroRNA-mediated drug resistance in breast cancer.
AB  - Chemoresistance is one of the major hurdles to overcome for the successful
      treatment of breast cancer. At present, there are several mechanisms proposed to
      explain drug resistance to chemotherapeutic agents, including decreased
      intracellular drug concentrations, mediated by drug transporters and metabolic
      enzymes; impaired cellular responses that affect cell cycle arrest, apoptosis,
      and DNA repair; the induction of signaling pathways that promote the progression
      of cancer cell populations; perturbations in DNA methylation and histone
      modifications; and alterations in the availability of drug targets. Both genetic
      and epigenetic theories have been put forward to explain the mechanisms of drug
      resistance. Recently, a small non-coding class of RNAs, known as microRNAs, has
      been identified as master regulators of key genes implicated in mechanisms of
      chemoresistance. This article reviews the role of microRNAs in regulating
      chemoresistance and highlights potential therapeutic targets for reversing miRNA
      mediated drug resistance. In the future, microRNA-based treatments, in
      combination with traditional chemotherapy, may be a new strategy for the clinical
      management of drug-resistant breast cancers.

PMID- 21949549
TI  - ABT-737 and/or folate reverse the PDGF-induced alterations in the mitochondrial
      apoptotic pathway in low-grade glioma patients.
AB  - Elevated activation of the platelet-derived growth factor (PDGF) pathway,
      apoptosis evasion phenotype, and global DNA hypomethylation are hallmarks
      frequently observed in cancers, such as in low-grade glioma (LGG). However, the
      orchestration of these malignant functions is not fully elucidated in LGG. Our
      study reveals that the co-presence of these hallmarks in the same LGG is frequent
      and confers poor prognosis in patients with LGG. Our data also indicate that the
      apoptosis evasion phenotype of these cells harboring a hypomethylation-induced
      activation of the PDGF pathway is associated with a hypomethylation of the bcl-xl
      and bcl-w genes and the phosphorylation and/or downregulation of three major pro
      apoptotic BH3-only proteins: PUMA, Bad, and Bim. Consistent with this, we
      demonstrate that the use of folate, a DNA-methylating agent, promotes the
      reprogramming of the sensitivity of glioma cells to ABT-737/etoposide-induced
      apoptosis and reduces the dose of ABT-737 required to promote etoposide-induced
      apoptosis. This work supports the idea that the inclusion of folate and/or ABT
      737 could be a promising adjuvant in the design of anti-glioma therapeutic
      protocols in clinical studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online
      version of this article (doi:10.1007/s13148-011-0035-5) contains supplementary
      material, which is available to authorized users.

PMID- 21949550
TI  - Epigenetic analyses in blood cells of men suspected of prostate cancer predict
      the outcome of biopsy better than serum PSA levels.
AB  - Lymphocytes from the peripheral blood of patients with prostate cancer-the most
      frequent (noncutaneous) tumor in men-display epigenetic aberrations (altered
      modes of allelic replication) characteristic of the malignant phenotype. The
      present study aims to determine whether replication aberrations add certainty to
      the suspicion of prostate cancer provided by the prostate-specific antigen (PSA)
      blood test. The allelic replication mode (whether synchronous or asynchronous)
      was exemplified for RB1 and AML1. These two genes normally exhibit a synchronous
      mode of allelic replication. Fluorescence in situ hybridization (FISH)
      replication assay was used for replication analyses. The FISH assays were applied
      to PHA-stimulated lymphocytes, established from peripheral blood samples of 35
      men referred to biopsy due to suspected prostate cancer. Following biopsy 13 out
      of these 35 men were found positive for prostate malignancy. The FISH assay
      showing asynchronous or synchronous RB1 and AML1 replication-was able to predict,
      respectively, the results of all biopsy-positive men and in 18 out of the 22
      biopsy-negative ones. These measurements, distinguishing biopsy-positive from
      biopsy-negative men, were highly significant (P < 10(-8); 100% sensitivity and
      81.8% specificity). Yet, distinguishing between the two groups of men based on
      the PSA measurements was nonsignificant (P > 0.70). The FISH replication assay
      applied to peripheral blood lymphocytes of 35 men referred for biopsy
      significantly predicted the outcome of the pathological examination, more
      precisely than the serum PSA test. As such, the epigenetic alteration offers a
      potential noninvasive blood marker, complementary to the PSA, for a preliminary
      prostate cancer diagnosis.

PMID- 21949552
TI  - Biomarkers of exposure and effect-interpretation in human risk assessment.
AB  - The effect of exposure to carcinogenic polycyclic aromatic hydrocarbons adsorbed
      onto respirable air particles (PM2.5, diameter < 2.5 MUm) on DNA adducts and
      chromosomal aberrations was repeatedly studied in Prague, Czech Republic, in
      groups of policemen working in the downtown area and in bus drivers. Personal
      exposure was evaluated using personal samplers during working shifts. DNA adducts
      were analyzed in lymphocytes by the (32)P-postlabeling assay and chromosomal
      aberrations were analyzed by conventional cytogenetic analysis and fluorescent in
      situ hybridization (FISH). The impact of environmental pollution on DNA adducts
      and chromosomal aberrations was studied in a total of 950 subjects. Our results
      suggest that the environmental exposure of nonsmokers to concentrations higher
      than 1 ng benzo[a]pyrene/m(3) represents a risk of DNA damage, as indicated by an
      increase in DNA adducts and the genomic frequency of translocations determined by
      FISH.

PMID- 21949553
TI  - Multi-tool formaldehyde measurement in simulated and real atmospheres for indoor
      air survey and concentration change monitoring.
AB  - Formaldehyde is of particular health concern since it is carcinogenic for human
      and ubiquitous in indoor air where people spend most of their time. Therefore, it
      is important to have suitable methods and techniques to measure its content in
      indoor air. In the present work, four different techniques have been tested in
      the INERIS exposure chamber and in indoor environments in comparison to a
      standard active method: passive sampling method based on the reaction of 2,4
      dinitrophenylhydrazine with formaldehyde, two on-line continuous monitoring
      systems based on fluorescence and UV measurements and a portable commercialised
      analyser based on electrochemical titration. Two formaldehyde concentrations,
      about 10 and 25 MUg m(-3) were generated in an exposure chamber under controlled
      conditions of temperature, relative humidity, and wind speed to simulate real
      conditions and assess potential influence on passive sampling and continuous
      systems response. Influence of sampling periods on passive sampling has also been
      evaluated. The real atmosphere experiments have been performed in four different
      indoor environments: an office, a furniture shop, a shopping mall, and
      residential dwellings in which several potential formaldehyde sources linked to
      household activities have been tested. The analytical and sampling problems
      associated with each measurement method have been identified and discussed. An
      overall agreement between each technique has been observed and continuous
      analyzers allowed for formaldehyde concentrations change monitoring and secondary
      formation of that pollutant observation.

PMID- 21949551
TI  - RNA Granules Living a Post-transcriptional Life: the Trypanosomes' Case.
AB  - Trypanosomes are protozoan parasites responsible for recalcitrant infectious
      diseases such as Sleeping sickness and Chagas disease in Africa and America,
      respectively. Their complex life-cycles are accompanied by alternation of forms
      specific of the insect vectors and vertebrate hosts, each with different
      metabolic and structural requirements. Unlike most other eukaryotes, these single
      cell microorganisms seem to control the expression of protein-coding genes mostly
      by mRNA degradation, silencing and translation efficiency. Recent evidence showed
      that genuine cytoplasmic Stress Granules are formed as a response to heat stress
      in Trypanosoma brucei, basically formed by stalled translation initiation
      complexes on mRNA. On the other hand, Processing bodies (P bodies) are
      constitutive components of cytoplasmic mRNA metabolism in trypanosomes, which
      could have an important role in translational repression. During physiological
      starvation conditions in trypanosomes, components from P bodies fuse with other
      ribonucleoprotein complexes to form mRNA granules, where transcripts are stored
      and protected from degradation in a quiescent state. Other novel types of foci
      with unknown function that are related to RNA metabolism can be found in these
      parasites, namely heat-induced granules containing the 5' to 3' exoribonuclease
      XRNA, and starvation-induced granules containing transfer RNA halves. Thus,
      trypanosomes make use of non-membranous structures as a strategy to
      compartmentalize ribonucleoprotein complexes in the cytoplasm, aiding to cope
      with stressful situations avoiding mRNA translation or degradation. The relevance
      of stress-induced foci in trypanosomes has yet to be scored, although recent
      evidence suggests that these cytoplasmic organelles are required for survival
      under adverse growing conditions.

PMID- 21949554
TI  - Riboflavin as an oral tracer for monitoring compliance in clinical research.
AB  - We studied urinary riboflavin as an objective biomarker of compliance in clinical
      research using a simplified method amenable to high throughput analysis. Six
      healthy women not taking vitamin supplements ingested a study pill containing
      riboflavin (32 mg) as an inactive tracer and the soy isoflavones daidzin (0.243
      mmole) and genistin (0.222 mmole) as active ingredients once daily for four days.
      Riboflavin and metabolites of the isoflavones were measured in urine samples
      obtained before and after each pill. Urinary excretion of riboflavin and
      metabolites of both isoflavones peaked within 8 hrs and remained higher than
      baseline for 24 hrs. Urinary excretion of riboflavin was also measured in 152
      additional women with unrestricted dietary supplement intakes. Mean and median
      urinary riboflavin concentrations in these women were 0.42 and 0.31 MUg/mL,
      respectively, compared to 0.2 MUg/mL during a riboflavin-restricted diet.
      Receiver operating characteristics (ROC) curves indicated that urinary riboflavin
      within 24 hrs after a 32 mg dose would perform well as a measure of compliance
      (all areas under the ROC curves >=0.84. Samples collected during the initial 8
      hrs after pill ingestion performed better as a compliance measure than later
      collections. In summary, compliance in a clinical study can be monitored in real
      time by incorporating 32 mg of riboflavin into study pills, with compliance
      indicated by urinary riboflavin levels increasing over individual baselines or to
      >=1.0 MUg/mL, with a false positive rate of being classified as compliant at <5%.

PMID- 21949555
TI  - CVSim: An Open-Source Cardiovascular Simulator for Teaching and Research.
AB  - CVSim is a lumped-parameter model of the human cardiovascular system that has
      been developed and used for research and for teaching quantitative physiology
      courses at MIT and Harvard Medical School since 1984. We present a brief
      historical background of lumped-parameter cardiovascular system models, followed
      by an overview of the development of the major versions of CVSim over a 25-year
      period in our laboratory. We describe the features and differences of four
      versions of CVSim that are freely available in open-source form via PhysioNet
      (http://physionet.org). These include a six-compartment cardiovascular model with
      an arterial baroreflex system, implemented in C for efficiency, with an X-based
      graphical user interface; a six-compartment model with a more extensive short
      term regulatory system and incorporating resting physiologic perturbations,
      available as a stand-alone MATLAB application; and a pair of elaborated versions
      consisting of 6- and 21-compartment computational models implemented in C, with a
      separate and enhanced Java graphical user interface. We conclude with a
      discussion of the educational and research applications for which we have used
      CVSim.

PMID- 21949556
TI  - Juvenile mice show greater flexibility in multiple choice reversal learning than
      adults.
AB  - We hypothesized that decision-making strategies in juvenile animals, rather than
      being immature, are optimized to navigate the uncertainty and instability likely
      to be encountered in the environment at the time of the animal's transition to
      independence. We tested juvenile and young adult mice on discrimination and
      reversal of a 4-choice and 2-choice odor-based foraging task. Juvenile mice (P26
      27) learned a 4-choice discrimination and reversal faster than adults (P60-70),
      making fewer perseverative and distraction errors. Juvenile mice had shorter
      choice latencies and more focused search strategies. In both ages, performance of
      the task was significantly impaired by a lesion of the dorsomedial frontal
      cortex. Our data show that the frontal cortex can support highly flexible
      behavior in juvenile mice at a time coincident with weaning and first
      independence. The unexpected developmental decline in flexibility of behavior one
      month later suggests that frontal cortex based executive function may not
      inevitably become more flexible with age, but rather may be developmentally tuned
      to optimize exploratory and exploitative behavior for each life stage.

PMID- 21949558
TI  - Alkyne- and 1,6-elimination- succinimidyl carbonate - terminated
      heterobifunctional poly(ethylene glycol) for reversible "Click" PEGylation.
AB  - A new heterobifunctional (succinimidyl carbonate, SC)-activated poly(ethylene
      glycol) (PEG) with a reversible 1,6-elimination linker and a terminal alkyne for
      "click" chemistry was synthesized with high efficiency and low polydispersity.
      The alpha-alkyne-omega-hydroxyl PEG was first prepared using trimethylsilyl-2
      propargyl alcohol as an initiator for ring-opening polymerization of ethylene
      oxide followed by mild deprotection with tetrabutylammonium fluoride. The hydroxy
      end was then modified with diglycolic anhydride to generate alpha-alkyne-omega
      carboxylic acid PEG. The reversible 1, 6-elimination linker was introduced by
      conjugation of a hydroxymethyl phenol followed by activation with N,N'
      disuccinimidyl carbonate to generate the heterobifunctional alpha-alkyne-omega-SC
      PEG. The terminal alkyne is available for "click" conjugation to azido ligands
      via 1,3-dipolar cycloaddition, and the succinimidyl carbonate will form a
      reversible conjugate to amines (e.g. in proteins) that can release the unaltered
      amine after base or enzyme catalyzed cleavage of the 1,6-linker.

PMID- 21949557
TI  - RIG-I like receptors and their signaling crosstalk in the regulation of antiviral
      immunity.
AB  - During virus infection, multiple immune signaling pathways are triggered, both
      within the host cell and bystander cells of an infected tissue. These pathways
      act in concert to mediate innate antiviral immunity and to initiate the
      inflammatory response against infection. The RIG-I-like receptor (RLR) family of
      pattern recognition receptors (PRRs) is a group of cytosolic RNA helicase
      proteins that can identify viral RNA as nonself via binding to pathogen
      associated molecular patter (PAMP) motifs within RNA ligands that accumulate
      during virus infection. This interaction then leads to triggering of an innate
      antiviral response within the infected cells through RLR induction of downstream
      effector molecules such as type I interferon (IFN) and other pro-inflammatory
      cytokines that serve to induce antiviral and inflammatory gene expression within
      the local tissue. Cellular regulation of RLR signaling is a critical process that
      can direct the outcome of infection and is essential for governance of the
      overall immune response and avoidance of immune toxicity. Mechanisms of positive
      and negative regulation of RLR signaling have been identified that include
      signaling crosstalk between RLR pathways and Nuclear Oligomerization Domain (NOD)
      Like Receptor (NLR) pathways and Caspase networks. Furthermore, many viruses have
      evolved mechanisms to target these pathways to promote enhanced replication and
      spread within the host. These virus-host interactions therefore carry important
      consequences for host immunity and viral pathogenesis. Understanding the pivotal
      role of RLRs in immune regulation and signaling crosstalk in antiviral immunity
      may provide new insights into therapeutic strategies for the control of virus
      infection and immunity.

PMID- 21949559
TI  - Electrochemical Surface Plasmon Resonance Spectroscopy at Bilayered Silver/Gold
      Films.
AB  - Bilayered silver/gold films (gold deposited on top of the silver film) were used
      as substrates for electrochemical surface plasmon resonance spectroscopy (EC
      SPR). EC-SPR responses of electrochemical deposition/stripping of copper and
      redox-induced conformation changes of cytochrome c immobilized onto self
      assembled monolayers preformed at these substrates were measured. Influence of
      the Ag layer thickness and the double-layer capacitance on the EC-SPR behavior
      was investigated. The results demonstrated that the bilayered Ag/Au metal films
      produce a sharper SPR dip profile than pure Au films and retain the high chemical
      stability of Au films. Contrary to the result by the Fresnel calculation that
      predicts a greater fraction of Ag in the bilayered film should result in a
      greater signal-to-noise ratio, the EC-SPR sensitivity is dependent on both the
      Ag/Au thickness ratio and the chemical modification of the surface. Factors
      affecting the overall SPR sensitivity at the bilayered films, such as the film
      morphology, potential-induced excess surface charges, and the adsorbate layer
      were investigated. Forming a compact adsorbate layer at the bilayered film
      diminishes the effect of potential-induce excess surface charges on the SPR
      signal and improves the overall EC-SPR sensitivity. For the case of redox-induced
      conformation changes of cytochrome c, the SPR signal obtained at the bilayered
      silver/gold film is 2.7 times as high as that at a pure gold film.

PMID- 21949560
TI  - Frailty in Patients with Cardiovascular Disease: Why, When, and How to Measure.
AB  - Frailty is a geriatric syndrome of impaired resistance to stressors due to a
      decline in physiologic reserve. Frailty and cardiovascular disease (CVD) share a
      common biological pathway, and CVD may accelerate the development of frailty.
      Frailty is identified in 25% to 50% of patients with CVD, depending on the
      frailty scale used and the population studied. Frail patients with CVD,
      especially those undergoing invasive procedures or suffering from coronary artery
      disease and heart failure, are more likely to suffer adverse outcomes as compared
      to their non-frail counterparts. Five-meter gait speed is a simple and effective
      way of objectively measuring frailty in patients with CVD and should be
      incorporated in risk assessment.

PMID- 21949562
TI  - Semiparametric Bayesian analysis of gene-environment interactions with error in
      measurement of environmental covariates and missing genetic data.
AB  - Case-control studies are widely used to detect gene-environment interactions in
      the etiology of complex diseases. Many variables that are of interest to
      biomedical researchers are difficult to measure on an individual level, e.g.
      nutrient intake, cigarette smoking exposure, long-term toxic exposure.
      Measurement error causes bias in parameter estimates, thus masking key features
      of data and leading to loss of power and spurious/masked associations. We develop
      a Bayesian methodology for analysis of case-control studies for the case when
      measurement error is present in an environmental covariate and the genetic
      variable has missing data. This approach offers several advantages. It allows
      prior information to enter the model to make estimation and inference more
      precise. The environmental covariates measured exactly are modeled completely
      nonparametrically. Further, information about the probability of disease can be
      incorporated in the estimation procedure to improve quality of parameter
      estimates, what cannot be done in conventional case-control studies. A unique
      feature of the procedure under investigation is that the analysis is based on a
      pseudo-likelihood function therefore conventional Bayesian techniques may not be
      technically correct. We propose an approach using Markov Chain Monte Carlo
      sampling as well as a computationally simple method based on an asymptotic
      posterior distribution. Simulation experiments demonstrated that our method
      produced parameter estimates that are nearly unbiased even for small sample
      sizes. An application of our method is illustrated using a population-based case
      control study of the association between calcium intake with the risk of
      colorectal adenoma development.

PMID- 21949561
TI  - STAT3 Inhibition by Microtubule-Targeted Drugs: Dual Molecular Effects of
      Chemotherapeutic Agents.
AB  - To improve the effectiveness of anti-cancer therapies, it is necessary to
      identify molecular targets that are essential to a tumor cell but dispensable in
      a normal cell. Increasing evidence indicates that the transcription factor STAT3,
      which regulates the expression of genes controlling proliferation, survival, and
      self-renewal, constitutes such a target. Recently it has been found that STAT3
      can associate with the cytoskeleton. Since many of the tumors in which STAT3 is
      activated, such as breast cancer and ovarian cancer, are responsive to drugs that
      target microtubules, we examined the effect of these compounds on STAT3. We found
      that microtubule stabilizers, such as paclitaxel, or microtubule inhibitors, such
      as vinorelbine, decrease the activating tyrosine phosphorylation of STAT3 in
      tumor cells and inhibit the expression of STAT3 target genes. Paclitaxel
      decreases the association between STAT3 and microtubules, and appears to decrease
      STAT3 phosphorylation through induction of a negative feedback regulator. The
      cytotoxic activity of paclitaxel in breast cancer cell lines correlates with its
      ability to decrease STAT3 phosphorylation. However, consistent with the necessity
      for expression of a negative regulator, treatment of resistant MDA-MB-231 cells
      with the DNA demethylating agent 5-azacytidine restores the ability of paclitaxel
      to block STAT3-dependent gene expression. Finally, the combination of paclitaxel
      and agents that directly target STAT3 has beneficial effects in killing STAT3
      dependent cell lines. Thus, microtubule-targeted agents may exert some of their
      effects by inhibiting STAT3, and understanding this interaction may be important
      for optimizing rational targeted cancer therapies.

PMID- 21949563
TI  - Quality Map Thresholding for De-noising of Complex-Valued fMRI Data and Its
      Application to ICA of fMRI.
AB  - Although functional magnetic resonance imaging (fMRI) data are acquired as
      complex-valued images, traditionally most fMRI studies only use the magnitude of
      the data. FMRI analysis in the complex domain promises to provide more
      statistically significant information; however, the noisy nature of the phase
      poses a challenge for successful study of fMRI by complex-valued signal
      processing algorithms. In this paper, we introduce a physiologically motivated de
      noising method that uses phase quality maps to successfully identify and
      eliminate noisy areas in the fMRI data so they can be used in individual and
      group studies. Additionally, we show how the developed de-noising method improves
      the results of complex-valued independent component analysis of fMRI data, a very
      successful tool for blind source separation of biomedical data.

PMID- 21949564
TI  - Access to Information About Stuttering and Societal Knowledge of Stuttering.
AB  - The purpose of this study was to examine societal knowledge of stuttering, access
      to information sources, and the influence of information sources on knowledge of
      stuttering. 185 participants from Northwest Ohio were surveyed. Results of the
      study indicated that the general public varies in their knowledge of stuttering
      and that majority of participants had not accessed information about stuttering,
      and the few who had, did so a long time ago. Finally, access to information
      sources had little influence on knowledge of stuttering. Implications for future
      research are discussed.

PMID- 21949565
TI  - Optical Coherence Tomography and Fibrous Cap Characterization.
AB  - The pathophysiology of acute coronary syndromes has long been associated with
      atherosclerotic plaque rupture. Inflammation, thinning, and disruption of the
      fibrous cap have been implicated with the final processes leading to plaque
      rupture, but confirmation of these mechanisms of coronary thrombosis in humans
      has been hampered by the lack of imaging methods with sufficient resolution to
      resolve fibrous cap characterization and thickness in vivo. Intravascular optical
      coherence tomography (OCT) provides images with micron-level axial and lateral
      resolution, enabling detailed visualization of micro-structural changes of the
      arterial wall. The present article provides an overview of the potential role of
      OCT in identifying and characterizing fibrous cap morphology, thickness, and
      inflammation in human coronary plaques.

PMID- 21949566
TI  - New Scores for the Assessment of Mitral Stenosis Using Real-Time Three
      Dimensional Echocardiography.
AB  - Nonsurgical management of patients with symptomatic mitral valve stenosis has
      been established as the therapeutic modality of choice for two decades. Catheter
      based balloon dilation of the stenotic valvular area has been shown, at least, as
      effective as surgical interventions. Unfavorable results of catheter-based
      interventions are largely due to unfavorable morphology of the valve apparatus,
      particularly leaflets calcification and subvalvular apparatus involvement. A
      mitral valve score has been proposed in Boston, MA, about two decades ago, based
      on morphologic assessment of mitral valve apparatus by two-dimensional (2D)
      echocardiography to predict successful balloon dilation of the mitral valve.
      Several other scores have been developed in the following years in order to more
      successfully predict balloon dilatation outcome. However, all those scores were
      based on 2D echocardiography, which is limited by ability to distinguish
      calcification and subvalvular involvement. The introduction of new matrix-based
      ultrasound probe has allowed 3D echocardiography (3DE) to provide more detailed
      morphologic analysis of mitral valve apparatus including calcification and
      subvalvular involvement. Recently, a new 3DE scoring system has been proposed by
      our group, which represents an important leap into refinement of the use of
      echocardiography guiding mitral valve interventions.

PMID- 21949567
TI  - Rewiring for adaptation.
AB  - The idea behind adaptive behavioral epidemiology is that groups and individuals
      respond to the knowledge of a disease threat by changing their habits to avoid
      interactions with those who are contagious. Network-based models take this
      adaptive behavior into account by allowing the network to "rewire" its
      connections.

PMID- 21949568
TI  - Metabolic Syndrome and Breast Cancer Risk: Is There a Role for Metformin?
AB  - Obesity is one of the most important known preventable causes of cancer,
      accounting for up to 20% of cancer deaths in women. Obese women have increased
      risk of dying from breast cancer as well as an increased risk of distant
      metastasis. Metabolic Syndrome (MetSyn) is a group of metabolic conditions that
      include 1) abdominal obesity, 2) atherogenic dyslipidemia, 3) elevated blood
      pressure, and 4) insulin resistance. MetSyn is known to promote the development
      of cardiovascular disease and diabetes and may be associated with increased
      breast cancer risk. Emerging evidence supports an association between mammary
      adipocytes and their secreted adipocytokines and breast cancer initiation and
      progression. Metformin (1,1-dimethylbiguanide hydrochloride) is a drug used to
      treat type 2 diabetes and MetSyn. We review the potential association between
      MetSyn in promoting breast cancer and emerging evidence for the use of metformin
      in cancer prevention.

PMID- 21949569
TI  - Galectin-1-mediated biochemical controls of melanoma and glioma aggressive
      behavior.
AB  - Gliomas and melanomas are associated with dismal prognosis because of their
      marked intrinsic resistance to proapoptotic stimuli, such as conventional
      chemotherapy and radiotherapy, as well as their ability to escape immune cell
      attacks. In addition, gliomas and melanomas display pronounced neoangiogenesis.
      Galectin-1 is a hypoxia-sensitive protein, which is abundantly secreted by glioma
      and melanoma cells, which displays marked proangiogenic effects. It also provides
      immune tolerogenic environments to melanoma and glioma cells through the killing
      of activated T cells that attack these tumor cells. Galectin-1 protects glioma
      and melanoma cells against cytotoxic insults (including chemotherapy and
      radiotherapy) through a direct role in the unfolded protein response. Altogether,
      these facts clearly point to galectin-1 as an important target to be combated in
      gliomas and melanomas in order to: (1) weaken the defenses of these two types of
      cancers against radiotherapy, chemotherapy and immunotherapy/vaccine therapy; and
      (2) reinforce antiangiogenic therapies. In the present article, we review the
      biochemical and molecular biology-related pathways controlled by galectin-1,
      which are actually beneficial for melanoma and glioma cells, and therefore
      detrimental for melanoma and glioma patients.

PMID- 21949570
TI  - p53 in stem cells.
AB  - p53 is well known as a "guardian of the genome" for differentiated cells, in
      which it induces cell cycle arrest and cell death after DNA damage and thus
      contributes to the maintenance of genomic stability. In addition to this tumor
      suppressor function for differentiated cells, p53 also plays an important role in
      stem cells. In this cell type, p53 not only ensures genomic integrity after
      genotoxic insults but also controls their proliferation and differentiation.
      Additionally, p53 provides an effective barrier for the generation of pluripotent
      stem cell-like cells from terminally differentiated cells. In this review, we
      summarize our current knowledge about p53 activities in embryonic, adult and
      induced pluripotent stem cells.

PMID- 21949572
TI  - Coronary computed tomography angiography in coronary artery disease.
AB  - AIM: To investigate the research directions of coronary computed tomography (CT)
      angiography in the diagnosis of coronary artery disease (CAD) based on a
      systematic review of the literature. METHODS: A search of articles on coronary CT
      angiography in the diagnosis of CAD was performed during a 6-year-period between
      2005 and 2010 from five main radiology journals namely, Radiology, American
      Journal of Roentgenology, European Radiology, European Journal of Radiology and
      British Journal of Radiology. Analysis of the references was focused on the
      research directions of coronary CT angiography with regard to the type of studies
      in terms of diagnostic value, application of dose-reduction strategies and
      resultant effective radiation doses with use of these techniques. RESULTS: One
      hundred and forty two studies were identified which met the selection criteria
      and were included in the analysis. 64-slice CT (single source and dual-source CT)
      dominated 78% of the coronary CT angiography studies. Prior to 2007, research was
      focused on the diagnostic value of coronary CT angiography, but since 2008 more
      attention has been paid to radiation dose reduction. Radiation dose was reported
      in 64 studies, representing 45% of total studies published in the five radiology
      journals. Various dose-saving strategies have been implemented and prospective
      electrocardiography-triggering and high pitch techniques were found to be the
      most effective approaches for radiation dose reduction, with the corresponding
      mean effective dose being 3.5 +/- 1.9 mSv and 1.7 +/- 0.6 mSv, respectively.
      CONCLUSION: This review shows that the current research in coronary CT
      angiography has shifted from the previous focus on diagnostic accuracy in CAD to
      more emphasis on radiation dose reduction.

PMID- 21949573
TI  - Percutaneous revascularization in a patient with anomalous origin of left main
      coronary artery.
AB  - Anomalous origin of the coronary artery from opposite coronary sinus is
      infrequently observed during coronary angiography. Percutaneous coronary
      intervention (PCI) of anomalous coronary artery is technically difficult and
      challenging. It requires appropriate selection of guide catheters for adequate
      stability, coaxial alignment and backup support during the intervention. We
      hereby report a rare case of anomalous origin of left main coronary artery (LM)
      from the right coronary sinus, having a retro-aortic course to the left side
      before its bifurcation into left anterior descending (LAD) and circumflex artery.
      The 59-year-old man had successful PCI of atherosclerotic LAD lesions. A 64-slice
      Multi-Detector Computed Tomography (MDCT) performed at 4 years of follow-up
      demonstrated patency of coronary stents and also delineated the origin and course
      of the anomalous LM. The case illustrates the rarity of anomalous LM, and
      describes technical issues during PCI and the role of MDCT in coronary anomaly
      imaging.

PMID- 21949571
TI  - Parallel effects of beta-adrenoceptor blockade on cardiac function and fatty acid
      oxidation in the diabetic heart: Confronting the maze.
AB  - Diabetic cardiomyopathy is a disease process in which diabetes produces a direct
      and continuous myocardial insult even in the absence of ischemic, hypertensive or
      valvular disease. The beta-blocking agents bisoprolol, carvedilol and metoprolol
      have been shown in large-scale randomized controlled trials to reduce heart
      failure mortality. In this review, we summarize the results of our studies
      investigating the effects of beta-blocking agents on cardiac function and
      metabolism in diabetic heart failure, and the complex inter-related mechanisms
      involved. Metoprolol inhibits fatty acid oxidation at the mitochondrial level but
      does not prevent lipotoxicity; its beneficial effects are more likely to be due
      to pro-survival effects of chronic treatment. These studies have expanded our
      understanding of the range of effects produced by beta-adrenergic blockade and
      show how interconnected the signaling pathways of function and metabolism are in
      the heart. Although our initial hypothesis that inhibition of fatty acid
      oxidation would be a key mechanism of action was disproved, unexpected results
      led us to some intriguing regulatory mechanisms of cardiac metabolism. The first
      was upstream stimulatory factor-2-mediated repression of transcriptional master
      regulator PGC-1alpha, most likely occurring as a consequence of the improved
      function; it is unclear whether this effect is unique to beta-blockers, although
      repression of carnitine palmitoyltransferase (CPT)-1 has not been reported with
      other drugs which improve function. The second was the identification of a range
      of covalent modifications which can regulate CPT-1 directly, mediated by a
      signalome at the level of the mitochondria. We also identified an important
      interaction between beta-adrenergic signaling and caveolins, which may be a key
      mechanism of action of beta-adrenergic blockade. Our experience with this
      labyrinthine signaling web illustrates that initial hypotheses and anticipated
      directions do not have to be right in order to open up meaningful directions or
      reveal new information.

PMID- 21949575
TI  - The effect of early canalith repositioning on benign paroxysmal positional
      vertigo on recurrence.
AB  - OBJECTIVES: Benign paroxysmal positional vertigo (BPPV) can be treated using a
      simple repositioning maneuver. This study demonstrates the effects of early
      repositioning therapy in patients with BPPV, especially with regard to
      recurrence. METHODS: We enrolled 138 consecutive patients who had been diagnosed
      with BPPV in the emergency rooms and ENT out-patient clinics of Chung-Ang
      University Hospital and Samyook Medical Center from January to June 2009. All
      patients immediately underwent appropriate canalith repositioning procedures
      (CRPs) depending on canalith type and location. The CRPs were performed daily
      until the patient's symptoms were resolved. The patients were classified into two
      groups according to the duration between symptom onset and initial treatment:
      less than 24 hours (early repositioning group, n=66) and greater 24 hours
      (delayed repositioning group, n=72). We prospectively compared the numbers of
      treatments received and the recurrence rates between the two groups. RESULTS:
      Follow-up periods ranged from 8 to 14 months, 77 cases involved posterior canal
      BPPV, 48 cases were lateral canal BPPV (of which 20 cases were cupulolithiasis),
      and 13 cases were multiple canal BPPV. BPPV recurrence was found in a total of 46
      patients (33.3%). The necessary numbers of CRPs were 2.3 for the early
      repositioning group and 2.5 for the late repositioning group, a difference that
      was not statistically significant (P=0.582). The early repositioning group showed
      a recurrence rate of 19.7%, and the delayed repositioning group showed a
      recurrence rate of 45.8% (P=0.002). CONCLUSION: Performing repositioning
      treatments as soon as possible after symptom onset may be an important factor in
      the prevention of BPVV recurrence.

PMID- 21949574
TI  - Can we develop effective combination antiangiogenic therapy for patients with
      hepatocellular carcinoma?
AB  - Antiangiogenic therapy has shown promise in the treatment of patients with
      hepatocellular carcinoma (HCC). Bevacizumab, sorafenib, and sunitinib showed
      efficacy in patients with HCC; and sorafenib is approved by the FDA for treatment
      of this cancer. In practice, the clinical benefit of these agents has been
      heterogeneous; and in patients who do respond, the benefit is modest and/or short
      lived. Recent advances in the molecular understanding of tumor angiogenesis along
      with the rapid development of targeted drug discovery have made it possible to
      explore novel combination therapy for HCC. We review the clinical trial results,
      discuss possible molecular mechanisms of resistance, and suggest novel
      combinations with antiangiogenic therapy.

PMID- 21949576
TI  - Does the kyphotic change decrease the risk of fall?
AB  - OBJECTIVES: Falls are a major problem in the elderly. Age-related degeneration of
      the human balance system increases the risk of falls. Kyphosis is a common
      condition of curvature of the upper spine in the elderly and its development
      occurs through degenerative change. However, relatively little is known about the
      effect of kyphotic changes on balance in the elderly. The aim of this study is to
      investigate the influence of kyphosis on the balance strategy through use of the
      motor control test (MCT) in computerized dynamic posturography. METHODS: Fifty
      healthy subjects who were not affected by other medical disorders that could
      affect gait or balance were enrolled in the study. By simulation of kyphotic
      condition through change of the angles of the line connecting the shoulder to the
      hip and the ankle axis by approximately 30 degrees , the latency and amplitude of
      the MCT were measured in upright and kyphotic condition. RESULTS: In the kyphotic
      condition, latency was shortened in backward movement. In forward movement,
      latency was shortened only in large stimulation. The amplitude in forward
      movement was decreased in kyphotic condition. However, the change of amplitude
      was not significant in large intensity backward movement in the same condition.
      CONCLUSION: Kyphotic condition decreases the latency of MCT, especially in
      backward movement. These findings imply that kyphotic condition may serve as a
      protective factor against falls.

PMID- 21949577
TI  - Nasopharynx as a microbiologic reservoir in chronic suppurative otitis media:
      preliminary study.
AB  - OBJECTIVES: The present study was designed to identify the correlations of
      bacterial strains of the middle ear and the nasopharynx in chronic suppurative
      otitis media (CSOM) patients who were scheduled for operations. METHODS: Sixty
      three patients with CSOM were enrolled in the study. Culture specimens were
      collected from the middle ear and nasopharynx of patients who were admitted for
      operation. Samples collections were performed 3 times; from the middle ear and
      nasophaynx at the admission day, from the middle ear during the operation, and
      from the external auditory canal post-operatively. Bacteria were identified by
      gram staining and biochemical tests. The correspondence rate of organisms which
      simultaneously exist in the middle ear and the nasopharynx was measured. RESULTS:
      Sixty-eight organisms were isolated from the middle ear and 57 organisms from the
      nasopharynx among 63 patients. Of 68 bacteria identified in middle ear, 26.52%
      (18 bacteria) corresponded with those of nasopharynx. MRSA had the high
      correspondence rate, and of 18 methicillin-resistant Staphylococcus aureus (MRSA)
      isolated from middle ear, 33.3% (6 bacteria) corresponded with nasophaynx.
      Meanwhile, 3 organisms of MRSA were detected from the external auditory canal
      post-operatively, although they were only found in nasopharynx pre-operatively.
      CONCLUSION: The current trend of middle ear swab alone for bacterial detection
      would be insufficient to identify the potent MRSA and impede early antibiotic
      intervention for the effective middle ear surgery. Therefore, it is necessary to
      perform nasopharynx cultures together with conventional middle ear culture to
      control potent risk for infection pre-operatively.

PMID- 21949578
TI  - Frequency-specific hearing results after surgery for chronic ear diseases.
AB  - OBJECTIVES: To analyze frequency-specific hearing results after surgery for
      chronic ear diseases while considering pathological findings and various surgical
      factors. METHODS: Patients who underwent surgical management of chronic otitis
      media were reviewed retrospectively (n=559). Using pure tone audiometry, air
      conduction (AC), bone conduction (BC), and air bone gap (ABG) change between pre-
      and post-operative tests were calculated for the frequencies of 250, 500, 1,000,
      2,000, 3,000, 4,000 (AC and BC), and 6,000 Hz (AC). Frequency-specific results
      were investigated, considering various surgical factors, such as type of surgery,
      type of ossiculoplasty and pathological findings. RESULTS: AC results in the
      intact canal wall mastoidectomy showed improvement at each frequency except
      4,000, 6,000 Hz. AC results in the tympanoplasty showed improvement at each
      frequency except 6,000 Hz. AC and ABG results in the open cavity mastoidectomy
      showed improvement only at the frequencies of 250, 500, 2,000 Hz. AC and ABG
      improved at low and mid frequencies but not in high frequencies above 3,000 Hz
      when ossicular reconstruction was conducted. AC and ABG results also improved at
      low and mid frequencies in the cholesteatoma, and ABG results improved at all
      frequencies except 3,000 Hz in the non-cholesteatoma. CONCLUSION: After chronic
      ear surgery, AC and ABG changes improved, primarily in the low and mid
      frequencies. Further evaluation and studies for post-operative hearing loss at
      high frequencies are recommended for rehabilitation of hearing ability after
      surgery.

PMID- 21949579
TI  - The internet as a source of information for patients prior to rhinoplasty.
AB  - OBJECTIVES: To determine the prevalence of Internet use by patients considering
      rhinoplasty and to identify the impact of such information on their decisions.
      METHODS: Prospective analysis of the impact of information received via the
      Internet by patients considering rhinoplasty on their decision-making prior to
      surgery. Eighty six patients, scheduled for post-traumatic or aesthetic
      rhinoplasty, received a questionnaire, consisting of 19 questions, which sought
      to evaluate their perception of the importance of the Internet information to
      them and also collected relevant demographic and sociological data. RESULTS:
      Respondents searched online for descriptions of medical procedures, information
      about how to contact other patients, pre- and post-operative pictures and making
      contact with a doctor. Patients considering aesthetic rhinoplasty received
      medical information from a third party or via the Internet. Individuals requiring
      post-traumatic surgical treatment were usually referred by family doctor.
      CONCLUSION: Patients planning nasal aesthetic surgery form their opinions after
      consulting friends and searching the Internet, which can act as an important
      medical assistance.

PMID- 21949580
TI  - The reconstruction of nasal septal perforation with high density porous
      polyethylene covered with fascia lata: an experimental study on rabbit model.
AB  - OBJECTIVES: Evaluation of a new material, high-density porous polyethylene
      (HDPP), which is covered with fascia lata, for experimental nasal septal
      perforation closure. METHODS: Twenty New Zealand albino rabbits were included and
      divided into study and control groups. A lateral incision was made from the
      lateral aspect of the left nares to the incisura nasomaxillaris. After exposure
      of the cavum nasi, the nasal mucoperichondrium was elevated bilaterally. A full
      thickness 0.5*0.5-cm perforation was created over the septum nasi with a No. 11
      surgical blade. A fascia lata graft was used for the study group. The HDPP was
      covered with fascia lata and placed under the elevated mucosa. HDPP without a
      fascial covering was used in the control group. Four months after the procedure,
      magnetic resonance imaging was performed to evaluate resorption of the material.
      The animals were sacrificed, and the nasal septum was completely removed.
      Macroscopic and histopathological examinations were performed on the nasal
      septum. RESULTS: All rabbits had survived after the 4-month period.
      Macroscopically, nine of 10 (90%) perforations were closed in the fascia lata
      covered HDPP group. Histopathological examination of these nine rabbits revealed
      that the continuity of cartilage was disturbed in the perforation areas.
      Granulation tissue was inverted in areas in which the cartilage continuity was
      disturbed. The HDPP had remained intact at the edge of the perforation. In the
      HDPP group, six of 10 implants were still perforated (60%) and four (40%) were
      closed. The fascia lata-covered HDPP implant had a significantly higher
      perforation closure rate than that of the HDPP implant alone (P<0.05).
      CONCLUSION: In cases of septal perforation, it is better to cover the HDPP
      implant with fascia lata. This covered implant can be used for the repair of
      nasal septal perforations. HDPP implants are easy to work with and avoid the
      increased operative time and morbidity associated with harvesting autografts.

PMID- 21949581
TI  - Medialization thyroplasty using autologous nasal septal cartilage for treating
      unilateral vocal fold paralysis.
AB  - OBJECTIVES: A persistent insufficiency of glottal closure is mostly a consequence
      of impaired unilateral vocal fold movement. Functional surgical treatment is
      required because of the consequential voice, breathing and swallowing
      impairments. The goal of the study was to determine the functional voice outcomes
      after medialization thyroplasty with using autologous septal cartilage from the
      nose. METHODS: External vocal fold medialization using autologous nasal septal
      cartilage was performed on 15 patients (6 females and 9 males; age range, 30 to
      57 years). Detailed functional examinations were performed for all the patients
      before and after the surgery and this included perceptual voice assessment,
      laryngostroboscopic examination and acoustic voice analysis. RESULTS: All the
      patients reported improvement of voice quality post-operatively.
      Laryngostroboscopy revealed almost complete glottal closure after surgery in the
      majority of patients. Acoustic and perceptual voice assessment showed significant
      improvement post-operatively. CONCLUSION: Medialization thyroplasty using an
      autologous nasal septal cartilage implant offers good tissue tolerability and
      significant improvement of the subjective and objective functional voice
      outcomes.

PMID- 21949582
TI  - A Polymorphism (rs1801018, Thr7Thr) of BCL2 is Associated with Papillary Thyroid
      Cancer in Korean Population.
AB  - OBJECTIVES: Among the apoptosis signals, B-cell CLL/lymphoma 2 (BCL2) is a well
      known regulator of apoptosis with anti-apoptotic properties. We investigated here
      whether single nucleotide polymorphisms (SNPs) of the BCL2 were associated with
      host susceptibility of papillary thyroid cancer (PTC) occurrence and
      clinicopathologic parameters. METHODS: Ninety-two PTC patients and 222 control
      subjects were recruited. One promoter SNP (rs2279115, -938A/C) and one synonymous
      SNP (rs1801018, Thr7Thr) in the BCL2 gene were selected and genotyped using
      direct sequencing. Multiple logistic regression models were performed to evaluate
      odds ratios, 95% confidence intervals, and P-values. RESULTS: rs1801018 of the
      BCL2 gene was not associated with the development of PTC. In the
      clinicopathologic features, rs1801018 SNP was associated with the number and
      location. The G allele frequency of rs1801018 in PTC patients with multifocality
      (13.3%) was about four-fold higher than that in PTC patients with unifocality
      (3.4%). The G allele frequency of rs1801018 in PTC patients with both lobes
      (15.4%) was increased by about five-fold, compared to PTC patients with one lobe
      (3.2%). CONCLUSION: The results suggest that synonymous SNP rs1801018 and the G
      allele of the BCL2 gene may be associated with the multifocality and bilaterality
      of PTC in Korean population.

PMID- 21949584
TI  - Recurrent and Massive Life Threatening Epistaxis due to Nasal Heroin Usage.
AB  - Epistaxis, active bleeding from the nose, is a common ear nose and throat
      emergency, and can be severe or even fatal. We report a severe life threatening
      recurrent massive nasal bleeding caused by intranasal heroin use that has not
      hitherto been reported in the English literature. A 24-year-old male who took
      heroin several times nasally presented with massive nasal bleeding. A blood
      transfusion and an operation to halt nasal bleeding were required. The patient
      did not experience a bleeding attack 2 months following cessation of nasal heroin
      use.

PMID- 21949583
TI  - Reversible Sensorineural Hearing Loss due to Pachymeningitis Associated with
      Elevated Serum MPO-ANCA.
AB  - Hypertrophic pachymeningitis is a progressive disease resulting in a diffuse
      thickening of dura mater due to inflammation, tumor or autoimmune diseases, but
      most cases are idiopathic. It is seldom reported to be related to sensorineural
      hearing loss, but it can cause sensorineural hearing loss which can be
      potentially reversed through treatment. Here, we report the case of a 54-year-old
      woman who had progressive, bilateral, worse in the left, sensorineural hearing
      loss and visual disturbance with an accompanying headache over several months.
      Brain MRI showed diffusely thickened dura mater, highly enhanced after gadolinium
      administration, which was consistent with pachymeningitis. It was assumed to be
      related to autoimmune pathogenesis on the basis of elevated serum myeloperoxidase
      antineutrophil cytoplasmic antibody (MPO-ANCA) titers. After empirical steroid
      and cyclophosphamide therapy, auditory impairment improved, especially in the
      high frequency region of the pure tone audiogram, and significant improvement in
      the word recognition test. Moreover, a follow-up MRI revealed much decreased
      enhancement of the dura mater, and the MPO-ANCA titer decreased to within the
      normal range. In the case of rapidly progressive sensorineural hearing loss or
      hearing impairment accompanying other cranial neuropathy, pachymeningitis should
      be taken into consideration, and brain MRI with gadolinium enhancement is the
      best method of detecting it. Also, to ensure proper treatment, a cautious
      evaluation including an ANCA work-up should be performed.

PMID- 21949585
TI  - Cell Cultivation on Porous Titanium Implants with Various Structures.
AB  - The paper presents data on the cultivation of human dermal fibroblasts and rabbit
      mesenchymal stromal cells on two types of porous titanium implants, i.e., those
      with irregular pores formed by pressed titanium particles and those with regular
      pores formed by the cohesion of one-size titanium particles inside the implant.
      The goal of this study was to determine what type of titanium implant porosity
      ensured its strongest interaction with cells. Cells were cultivated on implants
      for 7 days. During this period, they formed a confluent monolayer on the implant
      surface. Cells grown on titanium implants were monitored by scanning electron
      microscopy. Fibroblasts interaction with implants depended on the implant
      porosity structure. On implants with irregular pores cells were more spread. On
      implants with regular pores fibroblasts enveloped particles and were only
      occasionally bound with neighboring particles by small outgrowths. There was no
      tight interaction of particles inside the implant. In implants formed by pressed
      particles, cells grow not only on surface, but also in the depth of the implant.
      Thus, we suppose that a tighter interaction of cells with the titanium implant
      and, supposedly, tissues with the implant in the organism will take place in the
      variant when the implant structure is formed by pressed titanium particles, i.e.,
      cellular interaction was observed inside the implant. In implants with irregular
      pores, cells grew both on the surface and in the depth. Thus, cells exhibited
      more adequate interactions with irregular pore titanium implants in vitro and
      hopefully the same interaction will be true in tissues after the implantation of
      the prosthesis into the organism.

PMID- 21949586
TI  - The Effect of Synovial Fluid Enzymes on the Biodegradability of Collagen and
      Fibrin Clots.
AB  - Recently there has been a great deal of interest in the use of biomaterials to
      stimulate wound healing. This is largely due to their ability to centralize high
      concentrations of compounds known to promote wound healing at a needed location.
      Joints present a unique challenge to using scaffolds because of the presence of
      enzymes in synovial fluid which are known to degrade materials that would be
      stable in other parts of the body. The hypothesis of this study was that
      atelocollagen scaffolds would have greater resistance to enzymatic degradation
      than scaffolds made of gelatin, fibrin and whole blood. To test this hypothesis,
      collagen and fibrin-based scaffolds were placed in matrix metallopeptidase-1 (MMP
      1), elastase, and plasmin solutions at physiologic concentrations, and the
      degradation of each scaffold was measured at varying time points. The
      atelocollagen scaffolds had a significantly greater resistance to degradation by
      MMP-1, elastase and plasmin over the fibrin based scaffolds. The results suggest
      that atelocollagen-based scaffolds may provide some protection against premature
      degradation by synovial fluid enzymes over fibrin-based matrices.

PMID- 21949587
TI  - High-contrast Cu(I)-selective fluorescent probes based on synergistic electronic
      and conformational switching.
AB  - The design of fluorescent probes for the detection of redox-active transition
      metals such as Cu(I/II) is challenging due to potentially interfering metal
      induced non-radiative deactivation pathways. By using a ligand architecture with
      a built-in conformational switch that maximizes the change in donor potential
      upon metal binding and an electronically decoupled tunable pyrazoline fluorophore
      as acceptor, we systematically optimized the photoinduced electron transfer (PET)
      switching behavior of a series of Cu(I)-selective probes and achieved an
      excellent fluorescence enhancement of greater than 200-fold. Crystal structure
      analysis combined with NMR solution studies revealed significant conformational
      changes of the ligand framework upon Cu(I) coordination. The photophysical data
      are consistent with a kinetically controlled PET reaction involving only the
      ligand moiety, despite the fact that Cu(I)-mediated reductive quenching would be
      thermodynamically preferred. The study demonstrates that high-contrast ratios can
      be achieved even for redox-active metal cations, providing that the metal
      initiated quenching pathways are kinetically unfavorable.

PMID- 21949588
TI  - A practical, convergent route to the key precursor to the tetracycline
      antibiotics.
AB  - Here we describe a 5-step sequence to prepare the AB enone 1, the key precursor
      to fully synthetic tetracyclines, that begins with a diastereoselective Michael
      Claisen coupling of two simple starting materials, a cyclohexenone (compound 2
      or, in a refinement, a substituted variant, vide infra) and the isoxazole ester
      3. This advance defines an 8-step linear sequence to 6-deoxytetracycline
      antibiotics from three components of similar complexity (cyclohexenone 2,
      isoxazole ester 3, and structurally diverse D-ring precursors) in which
      sequential diastereoselective Michael-Claisen cyclization reactions form the A-
      and C-rings, respectively, of the linearly fused ABCD tetracycline skeleton. In
      addition to providing a readily scalable, practical route to fully synthetic
      tetracyclines of broad structural diversity, the sequence reported comprises a
      series of non-obvious stereoselective transformations, including a novel means
      for C12a hydroxylation.

PMID- 21949589
TI  - Diplopia Secondary to West Nile Virus Meningitis.

PMID- 21949590
TI  - ALTERED CALCIUM CURRENTS AND AXONAL GROWTH IN Nf1 HAPLOINSUFFICIENT MICE.
AB  - Mutations of the neurofibromin gene (NF1) cause neurofibromatosis type 1 (NF1), a
      disease in which learning disabilities are common. Learning deficits also are
      observed in mice with a heterozygous mutation of Nf1 (Nf1(+/-)). Dysregulation of
      regulated neurotransmitter release has been observed in Nf1(+/-) mice. However,
      the role of presynaptic voltage-gated Ca(2+) channels mediating this release has
      not been investigated. We investigated whether Ca(2+) currents and transmitter
      release were affected by reduced neurofibromin in Nf1(+/-) mice. Hippocampal
      Ca(2+) current density was greater in neurons from Nf1(+/-) mice and a greater
      fraction of Ca(2+) currents was activated at less depolarized potentials. In
      addition, release of the excitatory neurotransmitter, glutamate, was increased in
      neuronal cortical cultures from Nf1(+/-) mice. Dendritic complexity and axonal
      length were also increased in neurons Nf1(+/-) mice compared to wild-type
      neurons, linking loss of neurofibromin to developmental changes in hippocampal
      axonal/cytoskeletal dynamics. Collectively, these results show that altered
      Ca(2+) channel density and transmitter release, along with increased axonal
      growth may account for the abnormal nervous system functioning in NF1.

PMID- 21949591
TI  - VOLTAGE-GATED CALCIUM CHANNELS ARE NOT AFFECTED BY THE NOVEL ANTI-EPILEPTIC DRUG
      LACOSAMIDE.
AB  - The novel anti-epileptic drug lacosamide targets two proteins - voltage-gated
      sodium channels and collapsin response mediator protein 2 (CRMP-2) - suggesting
      dual modes of action for lacosamide. We recently identified the neurite outgrowth
      and axonal guidance protein CRMP-2 as a novel partner and regulator of the
      presynaptic N-type voltage-gated Ca(2+) channel (CaV2.2) [Brittain et al., J.
      Biol. Chem. 284: 31375-31390 (2009)]. Here we examined the effects of lacosamide
      on voltage-gated Ba(2+) channels. Lacosamide did not affect Ba(2+) currents via N
      and P/Q- channels in rat hippocampal neurons or L-type Ca(2+) channels in a
      mouse CNS neuronal cell line, respectively. N-type Ba(2+) currents, augmented by
      CRMP-2 expression, were also unaffected by acute or chronic lacosamide exposure.
      These results establish that the anti-epileptic mode of action of lacosamide does
      not involve these voltage-gated Ca(2+) channels.

PMID- 21949593
TI  - Quantitative Comparison of Protein Surface Coverage on Glass Slides and Silver
      Island Films in Metal-Enhanced Fluorescence-based Biosensing Applications.
AB  - The use of Metal-Enhanced Fluorescence (MEF) phenomenon in fluorescence-based
      bioassays affords for increased sensitivity to be realized by incorporating metal
      nanoparticles onto planar surfaces. The close-range interactions of metal
      fluorophores result in increased fluorescence emission from the bioassays, which
      in turn affords for the detection of target biomolecules at lower concentrations.
      Moreover, the use of silver nanoparticles increases the photostability of
      fluorophores improving the detectability of fluorescence emission under prolonged
      use of excitation light. Although numerous reports on MEF-based biosensing
      applications exist, the contribution of protein coverage on Silver Island Films
      (SIFs) on the increased fluorescence emission was never investigated. This work
      presents our findings on the quantitative comparison of protein surface coverage
      on SIFs and blank glass slides. In this regard, identical protein bioassay for a
      model protein (biotinylated bovine serum albumin, b-BSA) on these surfaces is
      constructed and the relative extent of protein surface coverage on SIFs and blank
      glass slides was determined using radio-labeled biomolecules. It was found that
      the total scintillation counts on SIFs and blank glass slides were similar for
      BSA concentrations ranging from 1 MUM to 1 pM, which implies that increased
      fluorescence in MEF-based biosensing applications is only due to metal
      fluorophore interactions.

PMID- 21949592
TI  - Metastasis Update: Human Prostate Carcinoma Invasion via Tubulogenesis.
AB  - This paper proposes that human prostate carcinoma primarily invades as a cohesive
      cell collective through a mechanism similar to embryonic tubulogenesis, instead
      of the popular epithelial-mesenchymal transformation (EMT) model. Evidence
      supporting a tubulogenesis model is presented, along with suggestions for
      additional research. Additionally, observations documenting cell adhesion
      molecule changes in tissue and stromal components are reviewed, allowing for
      comparisons between the current branching morphogenesis models and the
      tubulogenesis model. Finally, the implications of this model on prevailing views
      of therapeutic and diagnostic strategies for aggressive prostatic disease are
      considered.

PMID- 21949594
TI  - Plasmon-Enhanced Enzymatic Reactions: A Study of Nanoparticle-Enzyme Distance-
      and Nanoparticle Loading-Dependent Enzymatic Activity.
AB  - A detailed investigation of the dependence of the efficiency of plasmon-enhanced
      enzymatic reactions on the distance between silver island films (SIFs) and horse
      radish peroxidase (HRP) enzyme and on the loading of SIFs on glass surfaces is
      presented. Three different extent of loading of SIFs on glass slides were used:
      1) low, 2) medium and 3) high, which was characterized by using optical
      absorption spectroscopy and scanning electron microscopy. Streptavidin-linked HRP
      enzyme was deposited onto SIFs and glass slides by using three different
      strategies: strategy 1: biotin-avidin protein assay (distance between SIFs and
      HRP = 4-8 nm), strategy 2: self assembled monolayers (SAMs) (1-5 nm), strategy 3:
      polymer layer (1-5 nm). The efficiency of enzymatic conversion of O
      phenylenediamine dihydrochloride (OPD) to a colored product by HRP on SIFs and
      glass surfaces was assessed by optical absorption spectroscopy. The distance
      between SIFs and HRP and the extent of loading of SIFs on the glass surfaces were
      shown to have significant effect on the efficiency of plasmon-enhanced enzymatic
      reactions. In this regard, up to an %250 increase in enzymatic conversion of OPD
      was observed from SIFs with high loading using strategy 1. In addition, we have
      studied the potential of repeated use of SIFs in plasmon-enhanced enzymatic
      reactions.

PMID- 21949595
TI  - Broad-Spectrum Anti-Cancer Activity of O-Arylated Diazeniumdiolates.
AB  - O(2)-(2,4-Dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2
      diolate (JS-K) and O(2)-{2,4-dinitro-5-[4-(N-methylamino)be nzoyloxy]phenyl} 1
      (N,N-dimethylamino)diazen-1-ium-1,2-diolate (PABA/NO) are O(2)-arylated
      diazeniumdiolates that have shown promising in vivo activity in a variety of
      rodent cancer models, including prostate cancer, leukemia, liver cancer, multiple
      myeloma, and ovarian cancer. This compound class was designed to be activated for
      anti-cancer effects by glutathione-S-transferase (GST)-induced release of
      cytotoxic nitric oxide (NO), but mechanistic studies have implicated a variety of
      pathways, some GST/NO-related, some not. Current work is focused on improving
      formulations and other drug development activities, as well as exploring possible
      new applications of these agents and their analogs. The selectivity of these
      drugs for attacking tumors while exhibiting little toxicity toward normal tissues
      suggests considerable promise for the treatment of various tumor types.

PMID- 21949596
TI  - Ligand Fluorination to Optimize Preferential Oxidation (PROX) of Carbon Monoxide
      by Water-Soluble Rhodium Porphyrins.
AB  - Catalytic, low temperature preferential oxidation (PROX) of carbon monoxide by
      aqueous [5,10,15,20-tetrakis(4-sulfonatophenyl)-2,3,7,8,12,13,17,18
      octafluoroporphyrinato]rhodium(III) tetrasodium salt, (1[Rh(III)]) and
      [5,10,15,20-tetrakis(3-sulfonato-2,6-difluorophenyl)-2,3,7,8,12,13,17,18
      octafluoroporphyrinato]rhodium(III) tetrasodium salt, (2[Rh(III)]) is reported.
      The PROX reaction occurs at ambient temperature in buffered (4 <= pH <= 13)
      aqueous solutions. Fluorination on the porphyrin periphery is shown to increase
      the CO PROX reaction rate, shift the metal centered redox potentials, and acidify
      ligated water molecules. Most importantly, beta-fluorination increases the
      acidity of the rhodium hydride complex (pK(a) = 2.2 +/- 0.2 for 2[Rh-D]); the
      dramatically increased acidity of the Rh(III) hydride complex precludes proton
      reduction and hydrogen activation near neutral pH, thereby permitting oxidation
      of CO to be unaffected by the presence of H(2). This new fluorinated water
      soluble rhodium porphyrin-based homogenous catalyst system permits preferential
      oxidation of carbon monoxide in hydrogen gas streams at 308  degrees K using
      dioxygen or a sacrificial electron acceptor (indigo carmine) as the terminal
      oxidant.

PMID- 21949597
TI  - An SNP-Based Linkage Map for Zebrafish Reveals Sex Determination Loci.
AB  - A surprising diversity of mechanisms controls sex determination of vertebrate
      organisms, even among closely related species. Both genetic and temperature
      dependent systems of sex determination have been described in teleost fish. In
      the common zebrafish model organism, heteromorphic sex chromosomes are not
      observed, and the potential role of a genetic component of sex determination
      remains largely unknown. Here we report a genome-wide linkage study of sex
      determination in zebrafish using a novel SNP genetic map. We identified loci on
      zebrafish chromosomes 5 (LOD score 7.9) and 16 (LOD score 9.3) governing sex
      determination as a complex trait, rather than as an XY or ZW genetic system. Each
      of these loci contains a prominent candidate gene with a conserved role in sex
      determination across additional species that suggest potential mechanisms of sex
      determination in zebrafish. The chromosome 5 locus harbors dmrt1, a key gene in
      sex determination from fruit flies to humans; mutation of the human DMRT1
      ortholog is a cause of complete sex reversal of XY individuals. The chromosome 16
      locus harbors cyp21a2; mutation of the human CYP21A2 ortholog is one of the more
      common causes of pseudohermaphroditism. Mutation detection at each of these
      candidate genes within the zebrafish cross identified hypomorphic variants on the
      female-associated allele of each locus. The two loci together accounted for 16%
      of variance of the trait. Interacting environmental cues are likely to be an
      additional important component of sex determination in zebrafish.

PMID- 21949598
TI  - Risky Sexual Behaviors among a Sample of Gang-identified Youth in Los Angeles.
AB  - Gang youth are at an increased likelihood of participating in unsafe sexual
      behaviors and at an elevated risk of exposure to sexually transmitted infection
      (STIs), including HIV. This manuscript presents quantitative and qualitative data
      on sexual behaviors among a sample of predominately heterosexual, male gang youth
      aged 16 to 25 years interviewed in Los Angeles between 2006 and 2007 (n = 60). In
      particular, sexual identity, initiation and frequency of sex, and number of
      sexual partners; use of condoms, children, and other pregnancies; group sex; and
      STIs and sex with drug users. We argue that gang youth are a particular public
      health concern, due to their heightened risky sexual activity, and that
      behavioral interventions targeting gang youth need to include a component on
      reducing sexual risks and promoting safe sexual health.

PMID- 21949599
TI  - Observed Emotional and Behavioral Indicators of Motivation Predict School
      Readiness in Head Start Graduates.
AB  - Emotions and behaviors observed during challenging tasks are hypothesized to be
      valuable indicators of young children's motivation, the assessment of which may
      be particularly important for children at risk for school failure. The current
      study demonstrated reliability and concurrent validity of a new observational
      assessment of motivation in young children. Head Start graduates completed
      challenging puzzle and trivia tasks during their kindergarten year. Children's
      emotion expression and task engagement were assessed based on their observed
      facial and verbal expressions and behavioral cues. Hierarchical regression
      analyses revealed that observed persistence and shame predicted teacher ratings
      of children's academic achievement, whereas interest, anxiety, pride, shame, and
      persistence predicted children's social skills and learning-related behaviors.
      Children's emotional and behavioral responses to challenge thus appeared to be
      important indicators of school success. Observation of such responses may be a
      useful and valid alternative to self-report measures of motivation at this age.

PMID- 21949600
TI  - Outlier-Based Differential Expression Analysis in Proteomics Studies.
AB  - An active area in cancer biomarker research is the development of statistical
      methods to identify expression signatures reflecting the heterogeneity of cancer
      across affected individuals. Tomlins et al. [5] observed heterogeneous patterns
      of oncogene activation within several cancer types, and introduced a statistical
      method called Cancer Outlier Profile Analysis (COPA) to identify "cancer outlier
      genes". Several related statistical approaches have since been developed, but the
      operating characteristics of these procedures (e.g. power, false positive rate),
      have not yet been fully characterized, especially in a proteomics setting. Here,
      we use simulation to identify the degree to which an outlier pattern of
      differential expression must hold in order for outlier-based approaches to be
      more effective than mean-based approaches. We also propose a diagnostic procedure
      that characterizes the potentially unequal levels of differential expression in
      the tails and in the center of a distribution of expression values. We find that
      for sample sizes and effect sizes typical of proteomics studies, the outlier
      pattern must be strong in order for outlier-based analysis to provide a
      meaningful benefit. This is corroborated by analysis of proteomics data from a
      melanoma study, in which the differential expression is most often present
      throughout the distribution, rather than being concentrated in the tails, albeit
      with a few proteins showing expression patterns consistent with outlier
      expression.

PMID- 21949601
TI  - Antichlamydial antibodies, human fertility, and pregnancy wastage.
AB  - Genital infections with Chlamydia trachomatis (C. trachomatis) continue to be a
      worldwide epidemic. Immune response to chlamydia is important to both clearance
      of the disease and disease pathogenesis. Interindividual responses and current
      chlamydial control programs will have enormous effects on this disease and its
      control strategies. Humoral immune response to C. trachomatis occurs in humans
      and persistent antibody levels appear to be most directly correlated with more
      severe and longstanding disease and with reinfection. There is a close
      correlation between the presence of antichlamydial antibodies in females and
      tubal factor infertility; the closest associations have been found for antibodies
      against chlamydial heat shock proteins. The latter antibodies have also been
      shown to be useful among infertile patients with prior ectopic pregnancy, and
      their presence has been correlated with poor IVF outcomes, including early
      pregnancy loss. We review the existing literature on chlamydial antibody testing
      in infertile patients and present an algorithm for such testing in the infertile
      couple.

PMID- 21949602
TI  - Beliefs that influence cost-related medication non-adherence among the "haves"
      and "have nots" with chronic diseases.
AB  - BACKGROUND AND OBJECTIVE: Some patients continue taking their medication as
      prescribed despite serious financial pressures, while others with the ability to
      pay forego treatment due to cost concerns. The primary goal of this study was to
      explore how patients' beliefs about the necessity of treatment and treatment side
      effects, influence cost-related non-adherence (CRN). METHODS: 27,302 participants
      in the Harris Interactive Chronic Illness Panel completed an internet survey. The
      current study focused on two subsamples representing: (a) the most economically
      vulnerable survey respondents (ie, individuals with household incomes of
      US$25,000 per year or less and monthly out-of-pocket medication costs of at least
      US$60, n = 1321); and (b) respondents who were the most likely to have the
      financial resources to pay for medications (ie, those with incomes of US$125,000
      or more and monthly medication costs of less than US$60.00, n = 1195).
      Multivariate models were constructed for each group to determine the independent
      impact on CRN of perceived need for medications and side-effect concerns.
      Increased risk for CRN associated with depression and asthma diagnoses also was
      examined. RESULTS: Twenty-one percent of economically vulnerable respondents
      reported continuing to take their medication as prescribed despite serious cost
      pressures, while 14% of high-income respondents reported CRN despite apparently
      manageable out-of-pocket costs. Both low perceived need for medications and
      concerns about side-effects affected CRN risk in low-income and high-income
      groups. Within groups of both low-income and high-income respondents, depression
      and asthma significantly increased patients' odds of reporting CRN. CONCLUSION:
      Beyond objective financial measures, CRN is influenced by patient beliefs, which
      can influence the perceived value of prescription drugs. Addressing these
      beliefs, as well as the unique adherence concerns of patients with depression and
      asthma, could decrease CRN rates even if cost pressures themselves cannot be
      reduced.

PMID- 21949603
TI  - Promoting knowledge of statins in patients with low health literacy using an
      audio booklet.
AB  - BACKGROUND: Statins are generally well tolerated and effective at reducing a
      patient's risk of both primary and secondary cardiovascular events. Many patients
      who would benefit from statin therapy either do not adhere to or stop taking
      their statin medication within the first year. We developed an audio booklet
      targeted to low health literacy patients to teach them about the benefits and
      risks of statins to help the patients adhere to their statin therapy. METHODS:
      Through focus groups and an iterative design, an audio booklet was developed for
      both English-speaking and Spanish-speaking patients. We then compared the booklet
      with standard of care in 132 patients from our target patient population to
      measure its impact on knowledge and understanding of statins. RESULTS: The
      patients enjoyed the audio booklet and showed significant increases in knowledge
      after listening to it when compared with those who received the standard of care
      materials. CONCLUSION: The audio booklet shows promise as a tool that can be used
      effectively in clinical practice to teach patients about statin therapy.

PMID- 21949604
TI  - Public's attitudes towards community pharmacy in Qatar: a pilot study.
AB  - OBJECTIVES: To assess the public's attitudes towards the community pharmacist's
      role in Qatar, to investigate the public's use of community pharmacy, and to
      determine the public's views of and satisfaction with community pharmacy services
      currently provided in Qatar. MATERIALS AND METHODS: Three community pharmacies in
      Qatar were randomly selected as study sites. Patients 16 years of age and over
      who were able to communicate in English or Arabic were randomly approached and
      anonymously interviewed using a multipart pretested survey. RESULTS: Over 5
      weeks, 58 patients were interviewed (60% response rate). A total of 45% of
      respondents perceived community pharmacists as having a good balance between
      health and business matters. The physician was considered the first person to
      contact to answer drug- related questions by 50% of respondents. Most patients
      agreed that the community pharmacist should provide them with the medication
      directions of use (93%) and advise them about the treatment of minor ailments
      (79%); however, more than 70% didn't expect the community pharmacist to monitor
      their health progress or to perform any health screening. Half of the
      participants (52%) reported visiting the pharmacy at least monthly. The top
      factor that affected a patient's choice of any pharmacy was pharmacy location
      (90%). When asked about their views about community pharmacy services in Qatar,
      only 37% agreed that the pharmacist gave them sufficient time to discuss their
      problem and was knowledgeable enough to answer their questions. CONCLUSION: This
      pilot study suggested that the public has a poor understanding of the community
      pharmacist's role in monitoring drug therapy, performing health screening, and
      providing drug information. Several issues of concern were raised including
      insufficient pharmacist- patient contact time and unsatisfactory pharmacist
      knowledge. To advance pharmacy practice in Qatar, efforts may be warranted to
      address identified issues and to promote the community pharmacist's role in drug
      therapy monitoring, drug information provision, and health screening.

PMID- 21949605
TI  - Differences in taste between three polyethylene glycol preparations: a randomized
      double-blind study.
AB  - BACKGROUND AND AIM: Patients suffering from chronic constipation require long
      term, regular therapy with laxatives. Literature regarding patient preference and
      acceptance in polyethylene glycol preparations is scarce. Therefore, this
      research aimed to identify preference between the three polyethylene glycol 3350,
      namely Molaxole((r)), Movicol((r)), and Laxtra Orange((r)). Furthermore, taste is
      one of the most important factors leading to patients' adherence, particularly
      when the treatment lasts for a long time. METHODS: In this randomized, cross-over
      double-blind study, 100 volunteers were recruited by advertisement. The
      volunteers were invited to taste the preparations and grade the taste using a
      five-point hedonic scale (extremely poor taste [1] to extremely good taste [5]).
      The volunteers were then asked to choose the most palatable preparation. RESULTS:
      One hundred volunteers with a mean age of 35 years (range 20-61) were randomized
      (76 females). Molaxole((r)), Movicol((r)), and Laxtra Orange((r)) had a mean
      hedonic score of 2.76 (SD: 0.82), 2.81 (SD: 0.76) and 3.12 (SD: 0.82)
      respectively. The hedonic taste score for Laxtra Orange((r)) was significantly
      better than Molaxole((r)) (P = 0.001) and Movicol((r)) (P = 0.001). No difference
      was found between Molaxole((r)) and Movicol((r)) (P = 0.61). Molaxole((r)) was
      the most preferred preparation for 19 volunteers (19%), Movicol((r)) for 24
      volunteers (25%) and Laxtra Orange((r)) for 55 volunteers (56%). Two volunteers
      had no preference. The order in which volunteers tested the preparations had no
      influence on the taste results. No significant differences in age or gender were
      observed. CONCLUSION: Laxtra Orange((r)) was most palatable preparation. This may
      have implications for adherence in patients with chronic constipation.

PMID- 21949606
TI  - A review of studies concerning treatment adherence of patients with anxiety
      disorders.
AB  - OBJECTIVE: This paper aimed at describing the most consistent correlates and/or
      predictors of nonadherence to treatment of patients with different anxiety
      disorders. METHOD: The authors retrieved studies indexed in Pubmed/Medline,
      Psycinfo, and Isi Web of Knowledge using the following search terms: attrition OR
      dropout OR attrition rates OR patient dropouts OR treatment adherence AND anxiety
      disorders. Research was limited to articles published before January 2010.
      RESULTS: Sixteen studies were selected that investigated the impact of
      sociodemographic, clinical, or cognitive variables on adherence to treatment for
      anxiety disorders. While no consistent pattern of sociodemographic or clinical
      features associated with nonadherence emerged, all studies that investigated
      cognitive variables in panic disorder, social anxiety disorder, and obsessive
      compulsive disorder found that expectations and opinions about treatment were
      related to adherence. CONCLUSION: The findings of this study suggest that it is
      essential to consider anxiety disorder patients' beliefs about illness and
      treatment strategies to increase their compliance with the therapeutic plan.

PMID- 21949607
TI  - Future of radiation therapy for malignant melanoma in an era of newer, more
      effective biological agents.
AB  - The incidence of melanoma is rising. The primary initial treatment for melanoma
      continues to be wide local excision of the primary tumor and affected lymph
      nodes. Exceptions to wide local excision include cases where surgical excision
      may be cosmetically disfiguring or associated with increased morbidity and
      mortality. The role of definitive or adjuvant radiotherapy has largely been
      relegated to palliative measures because melanoma has been viewed as a
      prototypical radiotherapy-resistant cancer. However, the emerging clinical and
      radiobiological data summarized here suggests that many types of effective
      radiation therapy, such as radiosurgery for melanoma brain metastases, plaque
      brachytherapy for uveal melanoma, intensity modulated radiotherapy for melanoma
      of the head and neck, and adjuvant radiotherapy for selected high-risk, node
      positive patients can improve outcomes. Similarly, although certain
      chemotherapeutic agents and biologics have shown limited responses, long-term
      control for unresectable tumors or disseminated metastatic disease has been
      rather disappointing. Recently, several powerful new biologics and treatment
      combinations have yielded new hope for this patient group. The recent
      identification of several clinically linked melanoma gene mutations involved in
      mitogen-activated protein kinase (MAPK) pathway such as BRAF, NRAS, and cKIT has
      breathed new life into the drive to develop more effective therapies. Some of
      these new therapeutic approaches relate to DNA damage repair inhibitors, cellular
      immune system activation, and pharmacological cell cycle checkpoint manipulation.
      Others relate to the investigation of more effective targeting and dosing
      schedules for underutilized therapeutics, such as radiotherapy. This paper
      summarizes some of these new findings and attempts to give some context to the
      renaissance in melanoma therapeutics and the potential role for multimodality
      regimens, which include certain types of radiotherapy as aids to locoregional
      control in sensitive tissues.

PMID- 21949608
TI  - Systematic in-vitro evaluation of the NCI/NIH Developmental Therapeutics Program
      Approved Oncology Drug Set for the identification of a candidate drug repertoire
      for MLL-rearranged leukemia.
AB  - Despite significant progress made in the overall cure rate, the prognosis for
      relapsed and refractory malignancies in children remains extremely poor. Hence,
      there is an urgent need for studies that enable the timely selection of
      appropriate agents for Phase I clinical studies. The Pediatric Oncology
      Experimental Therapeutics Investigators' Consortium (POETIC) is systematically
      evaluating libraries of known and novel compounds for activity against subsets of
      high-risk pediatric malignancies with defined molecular aberrations for future
      clinical development. In this report, we describe the in-vitro activity of a
      diverse panel of approved oncology drugs against MLL-rearranged pediatric
      leukemia cell lines. Agents in the Approved Oncology Drug Set II (National Cancer
      Institute/National Institutes of Health Developmental Therapeutics Program) were
      evaluated by in-vitro cytotoxicity assays in pediatric acute lymphoblastic
      leukemia and acute myeloid leukemia cell lines with MLL gene rearrangements.
      Validation studies were carried out with patient leukemia cells in culture.
      Comparative analysis for toxicity against nonmalignant cells was evaluated in
      normal bone marrow stromal cells and normal human lymphocytes. Results from this
      study show that 42 of the 89 agents tested have measurable cytotoxicity against
      leukemia cells, and among these, 12 were effective against all five MLL
      rearranged cell lines (IC(50) [half maximal inhibitory concentration] < 1 MUM).
      These 12 agents include cladribine, dactinomycin, daunorubicin, docetaxel,
      etoposide, gemcitabine, mitomycin C, mitoxantrone, teniposide, topotecan,
      triethylenemelamine, and vinblastine. We show that the Approved Oncology Drug Set
      II contains a number of agents with potent antileukemic activity in the tested
      cell lines. As approved drugs, these agents have been used in clinical settings
      for many years for other malignancies, thus their toxicity profile,
      pharmacokinetics, and other properties are readily available. Further evaluation
      of their use in future clinical trials for pediatric leukemia with MLL
      abnormalities should be considered.

PMID- 21949609
TI  - Antihypertensive effects of astaxanthin.
AB  - Astaxanthin is a biological antioxidant naturally found in a wide variety of
      aquatic living organisms, and has shown various pharmacological activities, such
      as anti-inflammatory and antidiabetic activities. A recent study reported that
      the administration of astaxanthin induced a significant reduction in blood
      pressure and delayed the incidence of stroke in stroke-prone spontaneously
      hypertensive rats, suggesting that astaxanthin also has antihypertensive effect.
      In a study using aortic rings of spontaneously hypertensive rats, astaxanthin
      induced a significant reduction of the contractile responses of the aorta to
      alpha-adrenergic receptor agonist and angiotensin II, which may contribute to the
      antihypertensive effect of astaxanthin. In a histopathological study, astaxanthin
      decreased coronary artery wall thickness compared with the control, indicating
      the possibility that astaxanthin ameliorates hypertension-induced vascular
      remodeling. Astaxanthin has anti-inflammatory, antidiabetic, antihypertensive,
      and antioxidative activities; therefore, we should perform further studies to
      elucidate an antiatherogenic effect of astaxanthin.

PMID- 21949610
TI  - Impact of dyslipidemia on cardiovascular risk stratification of hypertensive
      patients and association of lipid profile with other cardiovascular risk factors:
      results from the ICEBERG study.
AB  - BACKGROUND: Hypertension, dyslipidemia, and other cardiovascular risk factors are
      linked epidemiologically, clinically, and metabolically. Intensive/Initial
      Cardiovascular Examination regarding Blood Pressure levels, Evaluation of Risk
      Groups (ICEBERG) study focuses on the effect of dyslipidemia on cardiovascular
      risk evaluation and association of lipid profile with other risk factors.
      PATIENTS AND METHODS: The ICEBERG study consisted of two sub-protocols: ICEBERG
      1, conducted at 20 university hospitals (Referral Group) and ICEBERG-2, conducted
      at 197 primary healthcare centers (Primary Care Group). Sub-protocol had two
      patient profiles: patients previously diagnosed with essential hypertension and
      under medical treatment (Treated Group) and patients with systolic blood pressure
      >=130 mmHg or diastolic blood pressure >=85 mmHg, with no antihypertensive
      treatment for at least 3 months before inclusion (Untreated Group). Dyslipidemia
      was evaluated and cardiovascular risk stratification was performed according to
      ESC/ESH guidelines. RESULTS: More than half of the treated and untreated subjects
      were classified into high or very high cardiovascular risk groups. In a total of
      1817 patients, the percentage of patients in "high" plus "very high" added risk
      groups increased to 55.2% in Treated Referral Group (p < 0.001), to 62.6% in
      Untreated Referral Group (p = 0.25) and to 60.7% in Untreated Primary Care Group
      (p < 0.001), by re-evaluation of patients' lipid values. CONCLUSIONS: Serum lipid
      levels are useful in stratifying hypertensive patients into cardiovascular risk
      groups more accurately, for appropriate antihypertensive treatment.

PMID- 21949611
TI  - Cuff inflation during ambulatory blood pressure monitoring and heart rate.
AB  - INTRODUCTION: Twenty four-hour ambulatory blood pressure monitoring is a
      clinically validated procedure in evaluation of blood pressure (BP). We
      hypothesised that the discomfort during cuff inflation would increase the heart
      rate (HR) measured with 24-h ambulatory BP monitoring compared to a following HR
      measurement with a 24-h Holter monitor. METHODS: The study population (n = 56)
      were recruited from the outpatient's clinic at the Department of Nephrology,
      Aalborg Hospital, Aarhus University Hospital at Aalborg, Denmark. All the
      patients had chronic kidney disease (CKD). We compared HR measured with a 24-h
      Holter monitor with a following HR measured by a 24-h ambulatory BP monitoring.
      RESULTS: We found a highly significant correlation between the HR measured with
      the Holter monitor and HR measured with 24-h ambulatory blood pressure monitoring
      (r = 0.77, p < 0.001). Using the Bland-Altman plot, the mean difference in HR was
      only 0.5 beat/min during 24 hours with acceptable limits of agreement for both
      high and low HR levels. Dividing the patients into groups according to
      betablocker treatment, body mass index, age, sex, angiotensin-converting enzyme
      inhibitor treatment, statins treatment, diuretic treatment, or calcium channel
      blocker treatment revealed similar results as described above. CONCLUSION: The
      results indicate that the discomfort induced by cuff inflation during 24-h
      ambulatory BP monitoring does not increase HR. Thus, 24-h ambulatory BP
      monitoring may be a reliable measurement of the BP among people with CKD.

PMID- 21949612
TI  - Effects of antihypertensive drugs on carotid intima-media thickness: Focus on
      angiotensin II receptor blockers. A review of randomized, controlled trials.
AB  - Carotid intima-media thickness (IMT) and plaques have been shown to have a strong
      continuous relationship with cardiovascular (CV) morbidity and mortality;
      therefore, carotid atherosclerosis, as assessed by ultrasonography, can be
      regarded as a reliable surrogate end-point for therapeutic interventions. In this
      survey, we report the results of 16 double blind, randomized, controlled studies
      comparing: 1) antihypertensive drugs versus placebo/no treatment (five trials
      including 3,215 patients); 2) different active antihypertensive drug regimens
      (five trials including 4,662 patients); 3) angiotensin-II receptor blockers
      (ARBs) versus other antihypertensive agents (six trials including 841 patients).
      Our main findings can be summarized as follows: I) Long-term antihypertensive
      treatment has a blunting effect on carotid IMT progression, regardless of types
      of drugs. II) Calcium-channel blockers (CCBs) are more effective than other
      antihypertensive drugs including diuretics, beta-blockers, and angiotensin
      converting-enzyme (ACE)-inhibitors in this blunting effect; III) the effect of
      ARBs compared to other antihypertensive regimens (mostly based on atenolol) on
      carotid atherosclerosis progression needs to be further elucidated, as a
      protective effect was demonstrated by some, but not all studies examined. Thus,
      further studies are needed to clarify the role of ARBs in this therapeutic area.

PMID- 21949613
TI  - Can nocturnal hypertension predict cardiovascular risk?
AB  - Nocturnal hypertension and non-dipping of blood pressure during sleep are
      distinct entities that often occur together and are regarded as important
      harbingers of poor cardiovascular prognosis. This review addresses several
      aspects related to these blood pressure abnormalities including definitions,
      diagnostic limitations, pathogenesis and associated patient profiles, prognostic
      significance, and therapeutic strategies. Taken together, persistent nocturnal
      hypertension and non-dipping blood pressure pattern, perhaps secondary to
      abnormal renal sodium handling and/or altered nocturnal sympathovagal balance,
      are strongly associated with deaths, cardiovascular events, and progressive loss
      of renal function, independent of daytime and 24-hour blood pressure. Several
      pharmacological and non-pharmacological approaches may restore nocturnal blood
      pressure and circadian blood pressure rhythm to normal; however, whether this
      translates to a clinically meaningful reduction in unfavorable cardiovascular and
      renal consequences remains to be seen.

PMID- 21949615
TI  - Current concepts in combination therapy for the treatment of hypertension:
      combined calcium channel blockers and RAAS inhibitors.
AB  - Recent guidelines for the management of hypertension recommend target blood
      pressures <140/90 mmHg in hypertensive patients, or <130/80 mmHg in subjects with
      diabetes, chronic kidney disease, or coronary artery disease. Despite the
      availability and efficacy of antihypertensive drugs, most hypertensive patients
      do not reach the recommended treatment targets with monotherapy, making
      combination therapy necessary to achieve the therapeutic goal. Combination
      therapy with 2 or more agents is the most effective method for achieving strict
      blood pressure goals. Fixed-dose combination simplifies treatment, reduces costs,
      and improves adherence. There are many drug choices for combination therapy, but
      few data are available about the efficacy and safety of some specific
      combinations. Combination therapy of calcium antagonists and inhibitors of the
      renin-angiotensin-aldosterone system (RAAS) are efficacious and safe, and have
      been considered rational by both the JNC 7 and the 2007 European Society of
      Hypertension - European Society of Cardiology guidelines for the management of
      arterial hypertension. The aim of this review is to discuss some relevant issues
      about the use of combinations with calcium channel blockers and RAAS inhibitors
      in the treatment of hypertension.

PMID- 21949614
TI  - Valsartan combination therapy in the management of hypertension - patient
      perspectives and clinical utility.
AB  - The morbidity and mortality benefits of lowering blood pressure (BP) in
      hypertensive patients are well established, with most individuals requiring
      multiple agents to achieve BP control. Considering the important role of the
      renin-angiotensin-aldosterone system (RAAS) in the pathophysiology of
      hypertension, a key component of combination therapy should include a RAAS
      inhibitor. Angiotensin receptor blockers (ARBs) lower BP, reduce cardiovascular
      risk, provide organ protection, and are among the best tolerated class of
      antihypertensive therapy. In this article, we discuss two ARB combinations
      (valsartan/hydrochlorothiazide [HCTZ] and amlodipine/valsartan), both of which
      are indicated for the treatment of hypertension in patients not adequately
      controlled on monotherapy and as initial therapy in patients likely to need
      multiple drugs to achieve BP goals. Randomized, double-blind studies that have
      assessed the antihypertensive efficacy and safety of these combinations in the
      first-line treatment of hypertensive patients are reviewed. Both valsartan/HCTZ
      and amlodipine/valsartan effectively lower BP and are well tolerated in a broad
      range of patients with hypertension, including difficult-to-treat populations
      such as those with severe BP elevations, prediabetes and diabetes, patients with
      the cardiometabolic syndrome, and individuals who are obese, elderly, or black.
      Also discussed herein are patient-focused perspectives related to the use of
      valsartan/HCTZ and amlodipine/valsartan, and the rationale for use of single-pill
      combinations as one approach to enhance patient compliance with antihypertensive
      therapy.

PMID- 21949616
TI  - De-stiffening drug therapy and blood pressure control.
AB  - In hypertensive subjects, cardiovascular risk reduction is critically related to
      the decrease of systolic blood pressure (SBP). De-stiffening therapy means that,
      in a controlled therapeutic trial of long duration, a selective reduction of SBP
      has been obtained in the studied group by comparison with the control group, and
      that this SBP reduction is due to a decrease of either arterial stiffness, or
      wave reflections, or both. Central SBP reduction and cardiovascular remodeling
      are specifically involved. Most protocols require the presence of an angiotensin
      II blocker, potentially associated with a diuretic compound and/or a calcium
      channel blocker. Cardiovascular outcomes are significantly reduced by comparison
      with the control group, particularly when this latter group involves
      administration of a beta-blocking agent.

PMID- 21949617
TI  - Complementary mechanisms of action and rationale for the fixed combination of
      perindopril and indapamide in treating hypertension - update on clinical utility.
AB  - Although reducing blood pressure is the most important approach to reduce
      cardiovascular outcomes in the hypertensive population, the majority of patients
      fail to attain the targets. Most patients with hypertension need at least 2
      antihypertensive agents to achieve blood pressure goals. The 2007 European
      hypertension guidelines state that combined therapy is needed when monotherapy
      does not attain blood pressure objectives and as a first-line treatment in high
      risk patients. This point has been reinforced in the 2009 update of the European
      guidelines. The advantages of combination therapy are well documented with the
      potential for increased antihypertensive efficacy as a result of different
      mechanisms of action, and a lower incidence of adverse effects because of the
      lower doses used and the possible compensatory responses. Moreover, the use of
      fixed dose combinations are specially recommended as they facilitate treatment
      compliance. The inhibition of the renin-angiotensin system appears to be very
      beneficial in the treatment of patients with hypertension along the
      cardiovascular continuum and the combination of a renin-angiotensin system
      inhibitor and a diuretic is particularly recommended. Many clinical trials have
      demonstrated the benefits of the fixed combination perindopril/indapamide in the
      treatment of hypertension. The aim of this manuscript is to update the published
      data on the efficacy and safety of this fixed combination.

PMID- 21949618
TI  - Endothelial function, blood pressure control, and risk modification: impact of
      irbesartan alone or in combination.
AB  - Irbesartan, an angiotensin II type 1 receptor antagonist, is approved as
      monotherapy, or in combination with other drugs, for the treatment of
      hypertension in many countries worldwide. Data in the literature suggest that
      irbesartan is effective for reducing blood pressure over a 24-hour period with
      once-daily administration, and slows the progression of renal disease in patients
      with hypertension and type 2 diabetes. Furthermore, irbesartan shows a good
      safety and tolerability profile, compared with angiotensin II inhibitors and
      other angiotensin II type 1 receptor antagonists. Thus, irbesartan appears to be
      a useful treatment option for patients with hypertension, including those with
      type 2 diabetes and nephropathy. Irbesartan has an inhibitory effect on the
      pressor response to angiotensin II and improves arterial stiffness, vascular
      endothelial dysfunction, and inflammation in hypertensive patients. There has
      been considerable interest recently in the renoprotective effect of irbesartan,
      which appears to be independent of reductions in blood pressure. In particular,
      mounting data suggests that irbesartan improves endothelial function, oxidative
      stress, and inflammation in the kidneys. Recent studies have highlighted a
      possible role for irbesartan in improving coronary artery inflammation and
      vascular dysfunction. In this review we summarize and comment on the most
      important data available with regard to antihypertensive effect, endothelial
      function improvement, and cardiovascular risk reduction with irbesartan.

PMID- 21949619
TI  - Evidence-based approach for managing hypertension in type 2 diabetes.
AB  - Blood pressure (BP) control is a critical part of managing patients with type 2
      diabetes. Perhaps it is the single most important aspect of diabetes care, which
      unlike hyperglycemia and dyslipidemia can reduce both micro- and macrovascular
      complications. Hypertension is more prevalent in individuals with diabetes than
      general population, and in most cases its treatment requires two or more
      pharmacological agents (about 30% of individuals with diabetes need 3 or more
      medications to control BP). In this article we describe the key evidence that has
      contributed to our understanding that reduced BP translates into positive micro-
      and macrovascular outcomes. We review the data supporting current recommendation
      for BP target < 130/80 mmHg. Two studies suggest that a lower BP goal could be
      even more beneficial. We also present the comparative benefits of various
      antihypertensive drugs in reducing diabetes-related micro- and macrovascular
      complications. Finally we propose an evidence-based algorithm of how to initiate
      and titrate antihypertensive pharmacotherapy in affected individuals. Overall,
      achieving BP < 130/80 mmHg is more important than searching for the "best"
      antihypertensive agent in patients with diabetes.

PMID- 21949620
TI  - Update on the role of candesartan in the optimal management of hypertension and
      cardiovascular risk reduction.
AB  - Hypertension is the most prevalent cardiovascular disease of adults and is a
      major risk factor for cardiovascular (CV) and cerebrovascular morbidity and
      mortality worldwide. Treatment of hypertension leads to reduction of CV morbidity
      and mortality through blood pressure reduction. The role of renin-angiotensin
      aldosterone system (RAAS) in the pathophysiology of hypertension is mainly
      through generation of potent vasoconstrictor angiotensin II, stimulation of
      aldosterone secretion, and increase in sympathetic activation. Angiotensin II
      receptor blockers such as candesartan, a long-acting agent, alter this system by
      blocking the activation of angiotensin I receptors. Several important clinical
      trials have tested the efficacy of candesartan with placebo, antihypertensive
      agents, or other agents that block the RAAS for the control of hypertension and
      reduction of key CV risk factors such as microalbuminuria, heart failure,
      retinopathy, and carotid intima medial thickness. Candesartan has been shown to
      be a well-tolerated and effective antihypertensive agent with positive metabolic
      characteristics and additional benefits on CV and cerebrovascular outcomes. The
      aim of this review is to discuss the pharmacology, efficacy, and safety of
      candesartan, with an overview of key hypertension and CV studies involving
      candesartan.

PMID- 21949621
TI  - Fixed combinations in the pragmatic management of hypertension: focus on
      aliskiren and hydrochlorothiazide as a single pill.
AB  - A majority of hypertensive patients need more than one antihypertensive drug to
      control their blood pressure. For this reason, most guidelines have introduced
      the possibility of prescribing fixed-dose combination therapies as first-line
      treatment in hypertension. Today, the concept of fixed-dose combinations has
      evolved and the term single pill combination might become more appropriate to
      reflect the large choice of drug combinations available on the market. Recently,
      a new single pill combination has been launched which combines the first direct
      renin inhibitor aliskiren and low doses of hydrochlorothiazide. This paper
      reviews the potential advantages of single pill combinations and presents the
      first results obtained with the aliskiren/HCTZ single pill combination in
      hypertension.

PMID- 21949622
TI  - Critical appraisal of the differential effects of antihypertensive agents on
      arterial stiffness.
AB  - Increased central arterial stiffness, involving accelerated vascular ageing of
      the aorta, is a powerful and independent risk factor for early mortality and
      provides prognostic information above and beyond traditional risk factors for
      cardiovascular disease (CVD). Central arterial stiffness is an important
      determinant of pulse pressure; therefore, any pathological increase may result in
      left ventricular hypertrophy and impaired coronary perfusion. Central artery
      stiffness can be assessed noninvasively by measurement of aortic pulse wave
      velocity, which is the gold standard for measurement of arterial stiffness.
      Earlier, it was believed that changes in arterial stiffness, which are primarily
      influenced by long-term pressure-dependent structural changes, may be slowed but
      not reversed by pharmacotherapy. Recent studies with drugs that inhibit the renin
      angiotensin-aldosterone system, advanced glycation end products crosslink
      breakers, and endothelin antagonists suggest that blood pressure (BP)-independent
      reduction and reversal of arterial stiffness are feasible. We review the recent
      literature on the differential effect of antihypertensive agents either as
      monotherapy or combination therapy on arterial stiffness. Arterial stiffness is
      an emerging therapeutic target for CVD risk reduction; however, further clinical
      trials are required to confirm whether BP-independent changes in arterial
      stiffness directly translate to a reduction in CVD events.

PMID- 21949623
TI  - Critical appraisal and pooled analysis of telmisartan alone or in combination
      with hydrochlorothiazide for achieving blood pressure goals.
AB  - Rigid control of blood pressure (BP) is essential to prevent cardiovascular
      disease. However, only about 40% of hypertensive patients undergoing
      pharmacological intervention with a single agent achieve their BP goals in
      contemporary clinical practice. Combined therapy using currently available agents
      is effective in maximizing treatment outcome, although it raises medical costs
      and decreases the drug compliance rate. To overcome such negative consequences, a
      combination tablet containing an angiotensin II receptor blocker (ARB) with a
      small dose of hydrochlorothiazide (HCTZ) is now available on the international
      market, including Japan. This article briefly describes the unique properties of
      telmisartan, a highly selective ARB for the angiotensin II type 1 receptor,
      including its long-acting characteristics and recent prospective multicenter
      randomized clinical trials, followed by a description of a newly-introduced
      combination tablet in Japan, which contains telmisartan and HCTZ. This article
      also reviews its safety and efficacy based on currently available evidence.
      Finally, evidence comparing telmisartan/HCTZ with other combination therapies is
      presented.

PMID- 21949624
TI  - Impact of telmisartan in modifying vascular risk.
AB  - Telmisartan, a selective angiotensin II type 1 receptor blocker (ARB), has been
      investigated in many trials, in particular, in order to assess its
      antihypertensive effect in various situations and its ability to protect organs
      susceptible to hypertension. In addition to its antihypertensive properties, it
      has positive metabolic and vascular effects (partly because of its sustained
      action). Several large-scale trials have focused on the effect of telmisartan on
      cardiovascular morbidity and mortality, including comparisons of that with an
      angiotensin-converting enzyme inhibitor in subjects at high vascular risk.
      Telmisartan was used in the largest ARB research programme (the Ongoing
      Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial
      [ONTARGET] and Telmisartan Randomized Assessment Study in ACE Intolerant Subjects
      with Cardiovascular Disease [TRANSCEND] trial).

PMID- 21949625
TI  - Critical appraisal of amlodipine and olmesartan medoxomil fixed-dose combination
      in achieving blood pressure goals.
AB  - Hypertension remains a significant health burden in the United States, with
      almost one in three adults affected, and is an independent risk factor for
      cardiovascular and renal disease. The goal of antihypertensive treatment is to
      reduce cardiovascular and renal morbidity and mortality by reducing blood
      pressure (BP). Guidelines recommend a target BP of <140/90 mmHg, with a more
      stringent goal of <130/80 mmHg for patients with diabetes and chronic renal
      disease. However, BP goal attainment rates remain low and most patients require
      therapy with two or more antihypertensive agents. Combination antihypertensive
      therapy usually employs agents from different classes, thus benefitting from
      complementary mechanisms of action to achieve greater BP control with fewer side
      effects. Patient adherence to therapy is enhanced by formulating treatments as
      fixed-dose (single-pill) combinations. One example is the combination of
      amlodipine, a dihydropyridine calcium channel blocker (CCB), with olmesartan
      medoxomil, an angiotensin receptor blocker (ARB). Here, the rationale for the use
      of CCB/ARB combination therapy is discussed, as well as the pharmacology and
      tolerability of the amlodipine/olmesartan medoxomil combination and its efficacy
      in terms of achieving BP goal in patients with hypertension. Advantages of its
      use from the patient's perspective are also discussed.

PMID- 21949626
TI  - Intravenous clevidipine for management of hypertension.
AB  - Hypertension remains one of the most prevalent diseases affecting our society,
      and its complications lead the list of causes of mortality all over the world.
      Most efforts to control the disease are unsuccessful, failing in at least two
      thirds of affected patients, despite the availability of multiple drugs for its
      treatment. The limited number of medications available for aggressive management
      of hypertensive crises has intensified the search for novel drugs that can
      achieve a rapid decrease in blood pressure without increasing the possible
      complications. Clevidipine is a novel, vasculoselective, dihydropyridine calcium
      channel blocker characterized by a very fast onset and offset of action.
      Metabolism of clevidipine does not occur in the liver or kidneys, and thus there
      are no restrictions to using clevidipine in patients with hepatic or renal
      dysfunction. This agent has been widely used to reduce blood pressure when oral
      therapy is not appropriate, and its use in the perioperative setting has been
      shown to be beneficial. This manuscript reviews the key characteristics of
      clevidipine and its role in the management of acute hypertension.

PMID- 21949627
TI  - Impact of olmesartan on blood pressure, endothelial function, and cardiovascular
      outcomes.
AB  - The vascular endothelium, the largest "organ" in the body, synthesizes and
      releases a wide spectrum of vasoactive substances into the circulation.
      Endothelial dysfunction links hypertension and other cardiovascular (CV) risk
      factors that promote the development of atherosclerotic plaque, CV disease, and
      fatal and nonfatal CV events. Blood pressure (BP) reduction is the most effective
      way to reduce CV risk in patients with hypertension, but it is unknown whether
      endothelial dysfunction is a cause or consequence of hypertension. Renin
      angiotensin-aldosterone system blockers improve endothelial function and have
      favorable vascular, metabolic, cardiac, and renoprotective effects that are
      independent of BP reduction. Olmesartan effectively reduces BP and also has
      vasoprotective properties, including reductions in endothelial dysfunction and
      inflammation, prevention of microalbuminuria, and reversal of vascular
      remodeling. Large-scale, long-term studies are needed to confirm that olmesartan
      has vasoprotective effects that are independent of BP control and to determine
      whether these pleiotropic effects translate into improved CV disease outcomes.

PMID- 21949628
TI  - Is tetrahydrobiopterin a therapeutic option in diabetic hypertensive patients?
AB  - Nitric oxide (NO) is an important regulator of vascular tone, and is also an
      antithrombotic, anti-inflammatory, antiproliferative, and antiatherogenic factor.
      Endothelial function is altered in patients with coronary artery disease, stroke,
      and peripheral artery disease, and endothelial dysfunction correlates with the
      risk factor profile for a patient. Hypertension and type 2 diabetes are risk
      factors for vascular disease, and are both pathologies characterized by loss of
      NO activity. Indeed, endothelial dysfunction is usually present in diabetic
      and/or hypertensive patients. Tetrahydrobiopterin is an essential cofactor for
      the NO synthase enzyme, and insufficiency of this cofactor leads to uncoupling of
      the enzyme, release of superoxide, endothelial dysfunction, progression of
      hypertension, and finally, proatherogenic effects. Tetrahydrobiopterin is also an
      important mediator of NO synthase regulation in type 2 diabetes and hypertension,
      and may be a rational therapeutic target to restore endothelial function and
      prevent vascular disease in these patients. The aim of this paper is to review
      the rationale for therapeutic strategies directed to biopterins as a target for
      vascular disease in type 2 diabetic hypertensive patients.

PMID- 21949629
TI  - Renoprotection, renin inhibition, and blood pressure control: the impact of
      aliskiren on integrated blood pressure control.
AB  - Hypertension (HTN) is an important factor in progressive loss of renal function.
      The kidney can be both a contributor to and a target of HTN. The functional
      integrity of the kidney is vital for the maintenance of cardiovascular
      homeostasis. Chronic activation of the renin system causes HTN and, ultimately,
      end-organ damage. Direct renin inhibitors (DRIs) inhibit plasma renin activity
      (PRA), thereby preventing the conversion of angiotensinogen to angiotensin I;
      consequently, the levels of both Ang I and Ang II are reduced. There is no
      compensatory increase in PRA activity with DRIs as seen with angiotensin
      converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs).
      There are reasons to speculate that renin inhibition might prove to be a superior
      strategy for blocking the renin-angiotensin-aldosterone system compared with
      ACEIs or ARBs. Evidence for the efficacy of aliskiren (a DRI) is considered to be
      relatively strong, based on published, short-term, double-blind, randomized,
      controlled trials showing that aliskiren is as effective as other
      antihypertensive agents in reducing blood pressure (BP), with no rebound effects
      on BP after treatment withdrawal. When combined with diuretics, fully additive BP
      reduction is seen. When given with an ACEI or ARB, aliskiren produces significant
      additional BP reduction indicative of complimentary pharmacology and more
      complete renin-angiotensin system blockade.

PMID- 21949630
TI  - Optimal management of hypertension in elderly patients.
AB  - Hypertension is a common and important modifiable risk factor for cardiovascular
      and kidney diseases. The prevalence of hypertension, particularly isolated
      systolic hypertension, increases with advancing age, and this is partly due to
      the age-related changes in the arterial tree, leading to an increase in arterial
      stiffness. Therapeutic lifestyle changes, such as reduced dietary sodium intake,
      weight loss, regular aerobic activity, and moderation of alcohol consumption,
      have been shown to benefit elderly patients with hypertension. Lowering blood
      pressure (BP) using pharmacological agents reduces the risk for cardiovascular
      morbidity and mortality, with no difference in risk reduction in elderly patients
      compared to younger hypertensives. Guidelines recommend a BP goal of <140/90 in
      hypertensive patients regardless of age and <130/80 in patients with concomitant
      diabetes or kidney disease, and lowering the BP further has not been shown to
      confer any additional benefit. Moreover, the choice of antihypertensive does not
      seem to be as important as the degree of BP lowering. Special considerations in
      the treatment of elderly hypertensive patients include cognitive impairment,
      dementia, orthostatic hypotension, and polypharmacy.

PMID- 21949631
TI  - Safety and tolerability of fixed antihypertensive combinations in blood pressure
      control: focus on olmesartan medoxomil and amlodipine combination.
AB  - Hypertension is a major health problem worldwide and remains underdiagnosed and
      undertreated. Although public awareness and control of hypertension have improved
      over the last decade, only one-third of hypertensive patients achieve the rather
      conservative blood pressure (BP) goal of <140/90 mmHg. Most hypertensive patients
      require more than one drug for optimum BP control. Expert panels recommend use of
      combination therapy with two or more medications for Stage 2 and higher
      hypertension and in high-risk patients. However, the use of multiple drugs
      reduces patient compliance. Fixed-dose combination therapy helps improve patient
      compliance and thus achieve the target BP. Dose titration of the individual
      constituent drugs is recommended before switching to an equivalent fixed-dose
      combination. Randomized, controlled trials have shown that the fixed-dose
      combination of amlodipine-olmesartan medoxomil is more effective in lowering BP
      than monotherapy with either of these agents, with a similar side effect profile.

PMID- 21949632
TI  - First-line treatment of hypertension: critical appraisal of potential role of
      aliskiren and hydrochlorothiazide in a fixed combination.
AB  - Arterial hypertension is one of the major diseases in the Western world. It is an
      independent cardiovascular risk factor and is associated with increased morbidity
      and mortality. Several drug classes have been shown to be effective in the
      treatment of hypertension. Aliskiren is a direct renin inhibitor and belongs to
      the class of renin-angiotensin-aldosterone system inhibitors. Several large
      studies have shown that aliskiren is effective in lowering blood pressure, and
      equivalent in this respect to the angiotensin-converting enzyme (ACE) inhibitors
      and the angiotensin receptor-1 blockers (ARBs). Furthermore, aliskiren has a
      safety and tolerability profile comparable with that of the ARBs and slightly
      better than that of the ACE inhibitors. From a pathophysiologic perspective, it
      can be combined with hydrochlorothiazide successfully, because it can block the
      diuretic-induced increase in plasma renin activity. Its combination with
      hydrochlorothiazide in a single pill has been investigated and shown to be
      superior to monotherapy with respect to blood pressure control and improvement in
      patient compliance with therapy. Further studies are needed to show whether
      aliskiren and its combination with hydrochlorothiazide is effective in preventing
      cardiovascular events and mortality when end organ damage is present.

PMID- 21949633
TI  - A critical appraisal of the clinical effectiveness of a fixed combination of
      valsartan, amlodipine, and hydrochlorothiazide in achieving blood pressure goals.
AB  - Recent guidelines for the treatment of hypertension have focused on the need for
      multiple medications to get most patients to goal blood pressure (BP). Two to
      three different classes of antihypertensive agents are frequently required,
      increasing the risk of poor compliance with therapy. Hence, the guidelines have
      recommended starting with combination therapy in patients with BP that is over 20
      mm Hg systolic or 10 mm Hg diastolic above goal. The latest advance in treatment
      regimen has been the development of triple-therapy combinations of an angiotensin
      receptor blocker, amlodipine, and hydrochlorothiazide. We review the
      pathophysiologic rationale for such a combination and the efficacy, safety, and
      tolerability of the first triple therapy that has become available: valsartan +
      amlodipine + hydrochlorothiazide. Finally, we suggest that use of triple therapy
      could improve the accuracy of diagnosing resistant hypertension, an increasingly
      prevalent and severe condition, by enhancing adherence to treatment and weeding
      out patients with pseudoresistance. This would allow for implementation of
      expensive and invasive workup only in those truly resistant patients in whom it
      is justified.

PMID- 21949634
TI  - Hypertension and other morbidities with Cushing's syndrome associated with
      corticosteroids: a review.
AB  - Corticosteroids constitute an ideal treatment for various inflammatory and
      autoimmune disorders due to their anti-inflammatory and immunomodulatory actions.
      However, corticosteroids have a considerable number of side effects, including
      hypertension, diabetes, lipid disorders, sleep apnea, osteoporosis, myopathy, and
      disorders of coagulation and fibrinolysis, which are components of Cushing's
      syndrome (CS). Corticosteroid-induced side effects are dependent on the
      formulation, route, dose, and time of exposure. However, the underlying
      pathogenetic mechanisms have not been clearly defined. A large body of evidence
      supports the role of an imbalance between vasoconstriction and vasodilation with
      possible links to nitric oxide, prostanoids, angiotensin II, arginine
      vasopressin, endothelins, catecholamines, neuropeptide Y, and atrial natriuretic
      peptide. Increased oxidative stress, renin-angiotensin system activation,
      increased pressor response, metabolic syndrome, and sleep apnea appear to be
      pathogenetically involved as well. The ideal treatment is the withdrawal of
      corticosteroids, which is most often impossible due to the exacerbation of the
      underlying disease. Alternatively, a careful plan, including the proper selection
      of the formulation, time, and route, should be made, and each side effect should
      be treated properly. The focus of the research should be to develop synthetic
      corticosteroids with anti-inflammatory effects but fewer metabolic effects, which
      so far has been unsuccessful.

PMID- 21949635
TI  - Long-term use and tolerability of irbesartan for control of hypertension.
AB  - In this review, we discuss the pharmacological and clinical properties of
      irbesartan, a noncompetitive angiotensin II receptor type 1 antagonist,
      successfully used for more than a decade in the treatment of essential
      hypertension. Irbesartan exerts its antihypertensive effect through an inhibitory
      effect on the pressure response to angiotensin II. Irbesartan 150-300 mg once
      daily confers a lasting effect over 24 hours, and its antihypertensive efficacy
      is further enhanced by the coadministration of hydrochlorothiazide. Additionally
      and partially beyond its blood pressure-lowering effect, irbesartan reduces left
      ventricular hypertrophy, favors right atrial remodeling in atrial fibrillation,
      and increases the likelihood of maintenance of sinus rhythm after cardioversion
      in atrial fibrillation. In addition, the renoprotective effects of irbesartan are
      well documented in the early and later stages of renal disease in type 2
      diabetics. Furthermore, both the therapeutic effectiveness and the placebo-like
      side effect profile contribute to a high adherence rate to the drug. Currently,
      irbesartan in monotherapy or combination therapy with hydrochlorothiazide
      represent a rationale pharmacologic approach for arterial hypertension and early
      stage and late-stage diabetic nephropathy in hypertensive type II diabetics.

PMID- 21949636
TI  - Clinical utility of fixed-combination telmisartan-amlodipine in the treatment of
      hypertension.
AB  - The majority of hypertensive patients, especially those with target organ damage,
      are likely to require multiple-drug therapy in order to reach blood pressure (BP)
      targets and reduce their risk of adverse vascular outcomes. The rationale for
      combination therapy with agents that block the renin-angiotensin system (RAS) and
      a calcium channel blocker (CCB) or diuretic is well founded in growing evidence.
      Recent published trials have shown that the combination of an RAS suppressor and
      a dihydropiridinic CCB would offer additional benefits independently of BP
      reduction. A telmisartan-amlodipine combination has demonstrated significantly
      greater BP reductions compared with each monotherapy component in the overall
      population, and in particular in patients with moderate to severe hypertension
      and high-risk patients. This combination is well tolerated with a safety profile
      similar to placebo and is consistent with the known safety profile of its
      monotherapy components.

PMID- 21949637
TI  - Short- and long-term physiologic and pharmacologic control of blood pressure in
      pediatric patients.
AB  - The incidence of hypertension is rising in the general population. A parallel
      trend is present in children and adolescents. This reflects more intensive
      treatment and improved patient survival after a wide range of serious systemic
      illnesses that can lead to hypertension. In addition, primary or essential
      hypertension is more prevalent because of the epidemic of obesity and metabolic
      syndrome in pediatric and adult patients of both genders and in all ethnic
      groups. As a consequence of the changing demographic pattern of hypertension,
      more patients are requiring therapy for elevated blood pressure. This review
      summarizes key aspects of the treatment for hypertension in pediatric patients
      and the long-term management of this problem, including nonpharmacologic
      strategies and drug treatment.

PMID- 21949638
TI  - Signals that trigger dendrite growth are identified.

PMID- 21949639
TI  - Transcriptome analysis of the Arabidopsis megaspore mother cell uncovers the
      importance of RNA helicases for plant germline development.
AB  - Germ line specification is a crucial step in the life cycle of all organisms. For
      sexual plant reproduction, the megaspore mother cell (MMC) is of crucial
      importance: it marks the first cell of the plant "germline" lineage that gets
      committed to undergo meiosis. One of the meiotic products, the functional
      megaspore, subsequently gives rise to the haploid, multicellular female
      gametophyte that harbours the female gametes. The MMC is formed by selection and
      differentiation of a single somatic, sub-epidermal cell in the ovule. The
      transcriptional network underlying MMC specification and differentiation is
      largely unknown. We provide the first transcriptome analysis of an MMC using the
      model plant Arabidopsis thaliana with a combination of laser-assisted
      microdissection and microarray hybridizations. Statistical analyses identified an
      over-representation of translational regulation control pathways and a
      significant enrichment of DEAD/DEAH-box helicases in the MMC transcriptome,
      paralleling important features of the animal germline. Analysis of two
      independent T-DNA insertion lines suggests an important role of an enriched
      helicase, MNEME (MEM), in MMC differentiation and the restriction of the germline
      fate to only one cell per ovule primordium. In heterozygous mem mutants,
      additional enlarged MMC-like cells, which sometimes initiate female gametophyte
      development, were observed at higher frequencies than in the wild type. This
      closely resembles the phenotype of mutants affected in the small RNA and DNA
      methylation pathways important for epigenetic regulation. Importantly, the mem
      phenotype shows features of apospory, as female gametophytes initiate from two
      non-sister cells in these mutants. Moreover, in mem gametophytic nuclei, both
      higher order chromatin structure and the distribution of LIKE HETEROCHROMATIN
      PROTEIN1 were affected, indicating epigenetic perturbations. In summary, the MMC
      transcriptome sets the stage for future functional characterization as
      illustrated by the identification of MEM, a novel gene involved in the
      restriction of germline fate.

PMID- 21949640
TI  - ESRRA-C11orf20 is a recurrent gene fusion in serous ovarian carcinoma.
AB  - Every year, ovarian cancer kills approximately 14,000 women in the United States
      and more than 140,000 women worldwide. Most of these deaths are caused by tumors
      of the serous histological type, which is rarely diagnosed before it has
      disseminated. By deep paired-end sequencing of mRNA from serous ovarian cancers,
      followed by deep sequencing of the corresponding genomic region, we identified a
      recurrent fusion transcript. The fusion transcript joins the 5' exons of ESRRA,
      encoding a ligand-independent member of the nuclear-hormone receptor superfamily,
      to the 3' exons of C11orf20, a conserved but uncharacterized gene located
      immediately upstream of ESRRA in the reference genome. To estimate the prevalence
      of the fusion, we tested 67 cases of serous ovarian cancer by RT-PCR and
      sequencing and confirmed its presence in 10 of these. Targeted resequencing of
      the corresponding genomic region from two fusion-positive tumor samples
      identified a nearly clonal chromosomal rearrangement positioning ESRRA upstream
      of C11orf20 in one tumor, and evidence of local copy number variation in the
      ESRRA locus in the second tumor. We hypothesize that the recurrent novel fusion
      transcript may play a role in pathogenesis of a substantial fraction of serous
      ovarian cancers and could provide a molecular marker for detection of the cancer.
      Gene fusions involving adjacent or nearby genes can readily escape detection but
      may play important roles in the development and progression of cancer.

PMID- 21949641
TI  - LIN-44/Wnt directs dendrite outgrowth through LIN-17/Frizzled in C. elegans
      Neurons.
AB  - Nervous system function requires proper development of two functional and
      morphological domains of neurons, axons and dendrites. Although both these
      domains are equally important for signal transmission, our understanding of
      dendrite development remains relatively poor. Here, we show that in C. elegans
      the Wnt ligand, LIN-44, and its Frizzled receptor, LIN-17, regulate dendrite
      development of the PQR oxygen sensory neuron. In lin-44 and lin-17 mutants, PQR
      dendrites fail to form, display stunted growth, or are misrouted. Manipulation of
      temporal and spatial expression of LIN-44, combined with cell-ablation
      experiments, indicates that this molecule is patterned during embryogenesis and
      acts as an attractive cue to define the site from which the dendrite emerges.
      Genetic interaction between lin-44 and lin-17 suggests that the LIN-44 signal is
      transmitted through the LIN-17 receptor, which acts cell autonomously in PQR.
      Furthermore, we provide evidence that LIN-17 interacts with another Wnt molecule,
      EGL-20, and functions in parallel to MIG-1/Frizzled in this process. Taken
      together, our results reveal a crucial role for Wnt and Frizzled molecules in
      regulating dendrite development in vivo.

PMID- 21949642
TI  - Living alone and alcohol-related mortality: a population-based cohort study from
      Finland.
AB  - BACKGROUND: Social isolation and living alone are increasingly common in
      industrialised countries. However, few studies have investigated the potential
      public health implications of this trend. We estimated the relative risk of death
      from alcohol-related causes among individuals living alone and determined whether
      this risk changed after a large reduction in alcohol prices. METHODS AND
      FINDINGS: We conducted a population-based natural experimental study of a change
      in the price of alcohol that occurred because of new laws enacted in Finland in
      January and March of 2004, utilising national registers. The data are based on an
      11% sample of the Finnish population aged 15-79 y supplemented with an oversample
      of deaths. The oversample covered 80% of all deaths during the periods January 1,
      2000-December 31, 2003 (the four years immediately before the price reduction of
      alcohol), and January 1, 2004-December 31, 2007 (the four years immediately after
      the price reduction). Alcohol-related mortality was defined using both underlying
      and contributory causes of death. During the 8-y follow-up about 18,200 persons
      died due to alcohol-related causes. Among married or cohabiting people the
      increase in alcohol-related mortality was small or non-existing between the
      periods 2000-2003 and 2004-2007, whereas for those living alone, this increase
      was substantial, especially in men and women aged 50-69 y. For liver disease in
      men, the most common fatal alcohol-related disease, the age-adjusted risk ratio
      associated with living alone was 3.7 (95% confidence interval 3.3, 4.1) before
      and 4.9 (95% CI 4.4, 5.4) after the price reduction (p<0.001 for difference in
      risk ratios). In women, the corresponding risk ratios were 1.7 (95% CI 1.4, 2.1)
      and 2.4 (95% CI 2.0, 2.9), respectively (p <= 0.01). Living alone was also
      associated with other mortality from alcohol-related diseases (range of risk
      ratios 2.3 to 8.0) as well as deaths from accidents and violence with alcohol as
      a contributing cause (risk ratios between 2.1 and 4.7), both before and after the
      price reduction. CONCLUSIONS: Living alone is associated with a substantially
      increased risk of alcohol-related mortality, irrespective of gender,
      socioeconomic status, or the specific cause of death. The greater availability of
      alcohol in Finland after legislation-instituted price reductions in the first
      three months of 2004 increased in particular the relative excess in fatal liver
      disease among individuals living alone.

PMID- 21949644
TI  - Research priorities for mental health and psychosocial support in humanitarian
      settings.

PMID- 21949643
TI  - Cost-effectiveness of early versus standard antiretroviral therapy in HIV
      infected adults in Haiti.
AB  - BACKGROUND: In a randomized clinical trial of early versus standard
      antiretroviral therapy (ART) in HIV-infected adults with a CD4 cell count between
      200 and 350 cells/mm3 in Haiti, early ART decreased mortality by 75%. We assessed
      the cost-effectiveness of early versus standard ART in this trial. METHODS AND
      FINDINGS: Trial data included use of ART and other medications, laboratory tests,
      outpatient visits, radiographic studies, procedures, and hospital services.
      Medication, laboratory, radiograph, labor, and overhead costs were from the study
      clinic, and hospital and procedure costs were from local providers. We evaluated
      cost per year of life saved (YLS), including patient and caregiver costs, with a
      median of 21 months and maximum of 36 months of follow-up, and with costs and
      life expectancy discounted at 3% per annum. Between 2005 and 2008, 816
      participants were enrolled and followed for a median of 21 months. Mean total
      costs per patient during the trial were US$1,381 for early ART and US$1,033 for
      standard ART. After excluding research-related laboratory tests without clinical
      benefit, costs were US$1,158 (early ART) and US$979 (standard ART). Early ART
      patients had higher mean costs for ART (US$398 versus US$81) but lower costs for
      non-ART medications, CD4 cell counts, clinically indicated tests, and radiographs
      (US$275 versus US$384). The cost-effectiveness ratio after a maximum of 3 years
      for early versus standard ART was US$3,975/YLS (95% CI US$2,129/YLS-US$9,979/YLS)
      including research-related tests, and US$2,050/YLS excluding research-related
      tests (95% CI US$722/YLS-US$5,537/YLS). CONCLUSIONS: Initiating ART in HIV
      infected adults with a CD4 cell count between 200 and 350 cells/mm3 in Haiti,
      consistent with World Health Organization advice, was cost-effective (US$/YLS <3
      times gross domestic product per capita) after a maximum of 3 years, after
      excluding research-related laboratory tests. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT00120510.

PMID- 21949647
TI  - A Salmonella small non-coding RNA facilitates bacterial invasion and
      intracellular replication by modulating the expression of virulence factors.
AB  - Small non-coding RNAs (sRNAs) that act as regulators of gene expression have been
      identified in all kingdoms of life, including microRNA (miRNA) and small
      interfering RNA (siRNA) in eukaryotic cells. Numerous sRNAs identified in
      Salmonella are encoded by genes located at Salmonella pathogenicity islands
      (SPIs) that are commonly found in pathogenic strains. Whether these sRNAs are
      important for Salmonella pathogenesis and virulence in animals has not been
      reported. In this study, we provide the first direct evidence that a
      pathogenicity island-encoded sRNA, IsrM, is important for Salmonella invasion of
      epithelial cells, intracellular replication inside macrophages, and virulence and
      colonization in mice. IsrM RNA is expressed in vitro under conditions resembling
      those during infection in the gastrointestinal tract. Furthermore, IsrM is found
      to be differentially expressed in vivo, with higher expression in the ileum than
      in the spleen. IsrM targets the mRNAs coding for SopA, a SPI-1 effector, and
      HilE, a global regulator of the expression of SPI-1 proteins, which are major
      virulence factors essential for bacterial invasion. Mutations in IsrM result in
      disregulation of expression of HilE and SopA, as well as other SPI-1 genes whose
      expression is regulated by HilE. Salmonella with deletion of isrM is defective in
      bacteria invasion of epithelial cells and intracellular replication/survival in
      macrophages. Moreover, Salmonella with mutations in isrM is attenuated in killing
      animals and defective in growth in the ileum and spleen in mice. Our study has
      shown that IsrM sRNA functions as a pathogenicity island-encoded sRNA directly
      involved in Salmonella pathogenesis in animals. Our results also suggest that
      sRNAs may represent a distinct class of virulence factors that are important for
      bacterial infection in vivo.

PMID- 21949648
TI  - Plague and climate: scales matter.
AB  - Plague is enzootic in wildlife populations of small mammals in central and
      eastern Asia, Africa, South and North America, and has been recognized recently
      as a reemerging threat to humans. Its causative agent Yersinia pestis relies on
      wild rodent hosts and flea vectors for its maintenance in nature. Climate
      influences all three components (i.e., bacteria, vectors, and hosts) of the
      plague system and is a likely factor to explain some of plague's variability from
      small and regional to large scales. Here, we review effects of climate variables
      on plague hosts and vectors from individual or population scales to studies on
      the whole plague system at a large scale. Upscaled versions of small-scale
      processes are often invoked to explain plague variability in time and space at
      larger scales, presumably because similar scale-independent mechanisms underlie
      these relationships. This linearity assumption is discussed in the light of
      recent research that suggests some of its limitations.

PMID- 21949649
TI  - Complex recombination patterns arising during geminivirus coinfections preserve
      and demarcate biologically important intra-genome interaction networks.
AB  - Genetic recombination is an important process during the evolution of many virus
      species and occurs particularly frequently amongst begomoviruses in the single
      stranded DNA virus family, Geminiviridae. As in many other recombining viruses it
      is apparent that non-random recombination breakpoint distributions observable
      within begomovirus genomes sampled from nature are the product of variations both
      in basal recombination rates across genomes and in the over-all viability of
      different recombinant genomes. Whereas factors influencing basal recombination
      rates might include local degrees of sequence similarity between recombining
      genomes, nucleic acid secondary structures and genomic sensitivity to nuclease
      attack or breakage, the viability of recombinant genomes could be influenced by
      the degree to which their co-evolved protein-protein and protein-nucleotide and
      nucleotide-nucleotide interactions are disreputable by recombination. Here we
      investigate patterns of recombination that occur over 120 day long experimental
      infections of tomato plants with the begomoviruses Tomato yellow leaf curl virus
      and Tomato leaf curl Comoros virus. We show that patterns of sequence exchange
      between these viruses can be extraordinarily complex and present clear evidence
      that factors such as local degrees of sequence similarity but not genomic
      secondary structure strongly influence where recombination breakpoints occur. It
      is also apparent from our experiment that over-all patterns of recombination are
      strongly influenced by selection against individual recombinants displaying
      disrupted intra-genomic interactions such as those required for proper protein
      and nucleic acid folding. Crucially, we find that selection favoring the
      preservation of co-evolved longer-range protein-protein and protein DNA
      interactions is so strong that its imprint can even be used to identify the exact
      sequence tracts involved in these interactions.

PMID- 21949650
TI  - Non-lytic, actin-based exit of intracellular parasites from C. elegans intestinal
      cells.
AB  - The intestine is a common site for invasion by intracellular pathogens, but
      little is known about how pathogens restructure and exit intestinal cells in
      vivo. The natural microsporidian parasite N. parisii invades intestinal cells of
      the nematode C. elegans, progresses through its life cycle, and then exits cells
      in a transmissible spore form. Here we show that N. parisii causes rearrangements
      of host actin inside intestinal cells as part of a novel parasite exit strategy.
      First, we show that N. parisii infection causes ectopic localization of the
      normally apical-restricted actin to the basolateral side of intestinal cells,
      where it often forms network-like structures. Soon after this actin
      relocalization, we find that gaps appear in the terminal web, a conserved
      cytoskeletal structure that could present a barrier to exit. Reducing actin
      expression creates terminal web gaps in the absence of infection, suggesting that
      infection-induced actin relocalization triggers gap formation. We show that
      terminal web gaps form at a distinct stage of infection, precisely timed to
      precede spore exit, and that all contagious animals exhibit gaps. Interestingly,
      we find that while perturbations in actin can create these gaps, actin is not
      required for infection progression or spore formation, but actin is required for
      spore exit. Finally, we show that despite large numbers of spores exiting
      intestinal cells, this exit does not cause cell lysis. These results provide
      insight into parasite manipulation of the host cytoskeleton and non-lytic escape
      from intestinal cells in vivo.

PMID- 21949651
TI  - A viral ubiquitin ligase has substrate preferential SUMO targeted ubiquitin
      ligase activity that counteracts intrinsic antiviral defence.
AB  - Intrinsic antiviral resistance represents the first line of intracellular defence
      against virus infection. During herpes simplex virus type-1 (HSV-1) infection
      this response can lead to the repression of viral gene expression but is
      counteracted by the viral ubiquitin ligase ICP0. Here we address the mechanisms
      by which ICP0 overcomes this antiviral response. We report that ICP0 induces the
      widespread proteasome-dependent degradation of SUMO-conjugated proteins during
      infection and has properties related to those of cellular SUMO-targeted ubiquitin
      ligases (STUbLs). Mutation of putative SUMO interaction motifs within ICP0 not
      only affects its ability to degrade SUMO conjugates, but also its capacity to
      stimulate HSV-1 lytic infection and reactivation from quiescence. We demonstrate
      that in the absence of this viral countermeasure the SUMO conjugation pathway
      plays an important role in mediating intrinsic antiviral resistance and the
      repression of HSV-1 infection. Using PML as a model substrate, we found that
      whilst ICP0 preferentially targets SUMO-modified isoforms of PML for degradation,
      it also induces the degradation of PML isoform I in a SUMO modification
      independent manner. PML was degraded by ICP0 more rapidly than the bulk of SUMO
      modified proteins in general, implying that the identity of a SUMO-modified
      protein, as well as the presence of SUMO modification, is involved in ICP0
      targeting. We conclude that ICP0 has dual targeting mechanisms involving both
      SUMO- and substrate-dependent targeting specificities in order to counteract
      intrinsic antiviral resistance to HSV-1 infection.

PMID- 21949652
TI  - Analysis of behavior and trafficking of dendritic cells within the brain during
      toxoplasmic encephalitis.
AB  - Under normal conditions the immune system has limited access to the brain;
      however, during toxoplasmic encephalitis (TE), large numbers of T cells and APCs
      accumulate within this site. A combination of real time imaging, transgenic
      reporter mice, and recombinant parasites allowed a comprehensive analysis of
      CD11c+ cells during TE. These studies reveal that the CNS CD11c+ cells consist of
      a mixture of microglia and dendritic cells (DCs) with distinct behavior
      associated with their ability to interact with parasites or effector T cells. The
      CNS DCs upregulated several chemokine receptors during TE, but none of these
      individual receptors tested was required for migration of DCs into the brain.
      However, this process was pertussis toxin sensitive and dependent on the integrin
      LFA-1, suggesting that the synergistic effect of signaling through multiple
      chemokine receptors, possibly leading to changes in the affinity of LFA-1, is
      involved in the recruitment/retention of DCs to the CNS and thus provides new
      insights into how the immune system accesses this unique site.

PMID- 21949653
TI  - HSV infection induces production of ROS, which potentiate signaling from pattern
      recognition receptors: role for S-glutathionylation of TRAF3 and 6.
AB  - The innate immune response constitutes the first line of defense against
      infections. Pattern recognition receptors recognize pathogen structures and
      trigger intracellular signaling pathways leading to cytokine and chemokine
      expression. Reactive oxygen species (ROS) are emerging as an important regulator
      of some of these pathways. ROS directly interact with signaling components or
      induce other post-translational modifications such as S-glutathionylation,
      thereby altering target function. Applying live microscopy, we have demonstrated
      that herpes simplex virus (HSV) infection induces early production of ROS that
      are required for the activation of NF-kappaB and IRF-3 pathways and the
      production of type I IFNs and ISGs. All the known receptors involved in the
      recognition of HSV were shown to be dependent on the cellular redox levels for
      successful signaling. In addition, we provide biochemical evidence suggesting S
      glutathionylation of TRAF family proteins to be important. In particular, by
      performing mutational studies we show that S-glutathionylation of a conserved
      cysteine residue of TRAF3 and TRAF6 is important for ROS-dependent activation of
      innate immune pathways. In conclusion, these findings demonstrate that ROS are
      essential for effective activation of signaling pathways leading to a successful
      innate immune response against HSV infection.

PMID- 21949654
TI  - Step-wise loss of bacterial flagellar torsion confers progressive phagocytic
      evasion.
AB  - Phagocytosis of bacteria by innate immune cells is a primary method of bacterial
      clearance during infection. However, the mechanisms by which the host cell
      recognizes bacteria and consequentially initiates phagocytosis are largely
      unclear. Previous studies of the bacterium Pseudomonas aeruginosa have indicated
      that bacterial flagella and flagellar motility play an important role in
      colonization of the host and, importantly, that loss of flagellar motility
      enables phagocytic evasion. Here we use molecular, cellular, and genetic methods
      to provide the first formal evidence that phagocytic cells recognize bacterial
      motility rather than flagella and initiate phagocytosis in response to this
      motility. We demonstrate that deletion of genes coding for the flagellar stator
      complex, which results in non-swimming bacteria that retain an initial flagellar
      structure, confers resistance to phagocytic binding and ingestion in several
      species of the gamma proteobacterial group of Gram-negative bacteria, indicative
      of a shared strategy for phagocytic evasion. Furthermore, we show for the first
      time that susceptibility to phagocytosis in swimming bacteria is proportional to
      mot gene function and, consequently, flagellar rotation since complementary
      genetically- and biochemically-modulated incremental decreases in flagellar
      motility result in corresponding and proportional phagocytic evasion. These
      findings identify that phagocytic cells respond to flagellar movement, which
      represents a novel mechanism for non-opsonized phagocytic recognition of
      pathogenic bacteria.

PMID- 21949655
TI  - Nrf2, a PPARgamma alternative pathway to promote CD36 expression on inflammatory
      macrophages: implication for malaria.
AB  - CD36 is the major receptor mediating nonopsonic phagocytosis of Plasmodium
      falciparum-parasitized erythrocytes by macrophages. Its expression on macrophages
      is mainly controlled by the nuclear receptor PPARgamma. Here, we demonstrate that
      inflammatory processes negatively regulate CD36 expression on human and murine
      macrophages, and hence decrease Plasmodium clearance directly favoring the
      worsening of malaria infection. This CD36 downregulation in inflammatory
      conditions is associated with a failure in the expression and activation of
      PPARgamma. Interestingly, using siRNA mediating knock down of Nrf2 in macrophages
      or Nrf2- and PPARgamma-deficient macrophages, we establish that in inflammatory
      conditions, the Nrf2 transcription factor controls CD36 expression independently
      of PPARgamma. In these conditions, Nrf2 activators, but not PPARgamma ligands,
      enhance CD36 expression and CD36-mediated Plasmodium phagocytosis. These results
      were confirmed in human macrophages and in vivo where only Nrf2 activators
      improve the outcome of severe malaria. Collectively, this report highlights that
      the Nrf2 transcription factor could be an alternative target to PPARgamma in the
      control of severe malaria through parasite clearance.

PMID- 21949656
TI  - Phosphodiesterase-4 inhibition alters gene expression and improves isoniazid
      mediated clearance of Mycobacterium tuberculosis in rabbit lungs.
AB  - Tuberculosis (TB) treatment is hampered by the long duration of antibiotic
      therapy required to achieve cure. This indolent response has been partly
      attributed to the ability of subpopulations of less metabolically active
      Mycobacterium tuberculosis (Mtb) to withstand killing by current anti-TB drugs.
      We have used immune modulation with a phosphodiesterase-4 (PDE4) inhibitor, CC
      3052, that reduces tumor necrosis factor alpha (TNF-alpha) production by
      increasing intracellular cAMP in macrophages, to examine the crosstalk between
      host and pathogen in rabbits with pulmonary TB during treatment with isoniazid
      (INH). Based on DNA microarray, changes in host gene expression during CC-3052
      treatment of Mtb infected rabbits support a link between PDE4 inhibition and
      specific down-regulation of the innate immune response. The overall pattern of
      host gene expression in the lungs of infected rabbits treated with CC-3052,
      compared to untreated rabbits, was similar to that described in vitro in resting
      Mtb infected macrophages, suggesting suboptimal macrophage activation. These
      alterations in host immunity were associated with corresponding down-regulation
      of a number of Mtb genes that have been associated with a metabolic shift towards
      dormancy. Moreover, treatment with CC-3052 and INH resulted in reduced expression
      of those genes associated with the bacterial response to INH. Importantly, CC
      3052 treatment of infected rabbits was associated with reduced ability of Mtb to
      withstand INH killing, shown by improved bacillary clearance, from the lungs of
      co-treated animals compared to rabbits treated with INH alone. The results of our
      study suggest that changes in Mtb gene expression, in response to changes in the
      host immune response, can alter the responsiveness of the bacteria to
      antimicrobial agents. These findings provide a basis for exploring the potential
      use of adjunctive immune modulation with PDE4 inhibitors to enhance the efficacy
      of existing anti-TB treatment.

PMID- 21949657
TI  - The receptor tyrosine kinase Alk controls neurofibromin functions in Drosophila
      growth and learning.
AB  - Anaplastic Lymphoma Kinase (Alk) is a Receptor Tyrosine Kinase (RTK) activated in
      several cancers, but with largely unknown physiological functions. We report two
      unexpected roles for the Drosophila ortholog dAlk, in body size determination and
      associative learning. Remarkably, reducing neuronal dAlk activity increased body
      size and enhanced associative learning, suggesting that its activation is
      inhibitory in both processes. Consistently, dAlk activation reduced body size and
      caused learning deficits resembling phenotypes of null mutations in dNf1, the Ras
      GTPase Activating Protein-encoding conserved ortholog of the Neurofibromatosis
      type 1 (NF1) disease gene. We show that dAlk and dNf1 co-localize extensively and
      interact functionally in the nervous system. Importantly, genetic or
      pharmacological inhibition of dAlk rescued the reduced body size, adult learning
      deficits, and Extracellular-Regulated-Kinase (ERK) overactivation dNf1 mutant
      phenotypes. These results identify dAlk as an upstream activator of dNf1
      regulated Ras signaling responsible for several dNf1 defects, and they implicate
      human Alk as a potential therapeutic target in NF1.

PMID- 21949658
TI  - Inactivation of Pmel alters melanosome shape but has only a subtle effect on
      visible pigmentation.
AB  - PMEL is an amyloidogenic protein that appears to be exclusively expressed in
      pigment cells and forms intralumenal fibrils within early stage melanosomes upon
      which eumelanins deposit in later stages. PMEL is well conserved among
      vertebrates, and allelic variants in several species are associated with reduced
      levels of eumelanin in epidermal tissues. However, in most of these cases it is
      not clear whether the allelic variants reflect gain-of-function or loss-of
      function, and no complete PMEL loss-of-function has been reported in a mammal.
      Here, we have created a mouse line in which the Pmel gene has been inactivated
      (Pmel-/-). These mice are fully viable, fertile, and display no obvious
      developmental defects. Melanosomes within Pmel-/- melanocytes are spherical in
      contrast to the oblong shape present in wild-type animals. This feature was
      documented in primary cultures of skin-derived melanocytes as well as in retinal
      pigment epithelium cells and in uveal melanocytes. Inactivation of Pmel has only
      a mild effect on the coat color phenotype in four different genetic backgrounds,
      with the clearest effect in mice also carrying the brown/Tyrp1 mutation. This
      phenotype, which is similar to that observed with the spontaneous silver mutation
      in mice, strongly suggests that other previously described alleles in vertebrates
      with more striking effects on pigmentation are dominant-negative mutations.
      Despite a mild effect on visible pigmentation, inactivation of Pmel led to a
      substantial reduction in eumelanin content in hair, which demonstrates that PMEL
      has a critical role for maintaining efficient epidermal pigmentation.

PMID- 21949659
TI  - Mutations in or near the transmembrane domain alter PMEL amyloid formation from
      functional to pathogenic.
AB  - PMEL is a pigment cell-specific protein that forms physiological amyloid fibrils
      upon which melanins ultimately deposit in the lumen of the pigment organelle, the
      melanosome. Whereas hypomorphic PMEL mutations in several species result in a
      mild pigment dilution that is inherited in a recessive manner, PMEL alleles found
      in the Dominant white (DW) chicken and Silver horse (HoSi)--which bear mutations
      that alter the PMEL transmembrane domain (TMD) and that are thus outside the
      amyloid core--are associated with a striking loss of pigmentation that is
      inherited in a dominant fashion. Here we show that the DW and HoSi mutations
      alter PMEL TMD oligomerization and/or association with membranes, with consequent
      formation of aberrantly packed fibrils. The aberrant fibrils are associated with
      a loss of pigmentation in cultured melanocytes, suggesting that they inhibit
      melanin production and/or melanosome integrity. A secondary mutation in the Smoky
      chicken, which reverts the dominant DW phenotype, prevents the accumulation of
      PMEL in fibrillogenic compartments and thus averts DW-associated pigment loss; a
      secondary mutation found in the Dun chicken likely dampens a HoSi-like dominant
      mutation in a similar manner. We propose that the DW and HoSi mutations alter the
      normally benign amyloid to a pathogenic form that antagonizes melanosome
      function, and that the secondary mutations found in the Smoky and Dun chickens
      revert or dampen pathogenicity by functioning as null alleles, thus preventing
      the formation of aberrant fibrils. We speculate that PMEL mutations can model the
      conversion between physiological and pathological amyloid.

PMID- 21949661
TI  - Synthesis characterization and biological activity study of new schiff and
      mannich bases and some metal complexes derived from isatin and dithiooxamide.
AB  - Two new Schiff and Mannich bases, namely, 1-Morpholinomethyl-3(1' -N
      dithiooxamide)iminoisatin (L(I)H) and 1-diphenylaminomethyl-3-1'-N
      dithiooxamide)iminoisatin (L(II)H), were prepared from condensation reaction of
      new Schiff base 3-(1'-N-dithiooxamide)iminoisatin (SBH) with morpholine or
      diphenylamine respectively in presence of formaldehyde . The structures were
      characterized by IR, (1)HNMR, mass spectrometry, and CHN analyses. Metal
      complexes of the two ligands were synthesized, and their structures were
      characterized by elemental analyses, atomic absorption, IR and UV-visible
      spectra, molar conductivity, and magnetic moment determination. All complexes
      showed octahedral geometries except palladium complexes which were square planar.
      The biological activity of the prepared compounds and some selected metal
      complexes was tested against three types of bacteria and against cell line of
      human epidermoid larynx carcinoma (Hep-2).

PMID- 21949660
TI  - Genetic variants at chromosomes 2q35, 5p12, 6q25.1, 10q26.13, and 16q12.1
      influence the risk of breast cancer in men.
AB  - Male breast cancer accounts for approximately 1% of all breast cancer. To date,
      risk factors for male breast cancer are poorly defined, but certain risk factors
      and genetic features appear common to both male and female breast cancer. Genome
      wide association studies (GWAS) have recently identified common single nucleotide
      polymorphisms (SNPs) that influence female breast cancer risk; 12 of these have
      been independently replicated. To examine if these variants contribute to male
      breast cancer risk, we genotyped 433 male breast cancer cases and 1,569 controls.
      Five SNPs showed a statistically significant association with male breast cancer:
      rs13387042 (2q35) (odds ratio (OR)  = 1.30, p = 7.98*10-4), rs10941679 (5p12) (OR
      = 1.26, p = 0.007), rs9383938 (6q25.1) (OR = 1.39, p = 0.004), rs2981579 (FGFR2)
      (OR = 1.18, p = 0.03), and rs3803662 (TOX3) (OR = 1.48, p = 4.04*10-6). Comparing
      the ORs for male breast cancer with the published ORs for female breast cancer,
      three SNPs--rs13387042 (2q35), rs3803662 (TOX3), and rs6504950 (COX11)--showed
      significant differences in ORs (p<0.05) between sexes. Breast cancer is a
      heterogeneous disease; the relative risks associated with loci identified to date
      show subtype and, based on these data, gender specificity. Additional studies of
      well-defined patient subgroups could provide further insight into the biological
      basis of breast cancer development.

PMID- 21949662
TI  - Dietary restriction ameliorates diabetic nephropathy through anti-inflammatory
      effects and regulation of the autophagy via restoration of Sirt1 in diabetic
      Wistar fatty (fa/fa) rats: a model of type 2 diabetes.
AB  - AIM: Despite the beneficial effects of dietary restriction (DR) on lifespan, age
      related diseases, including diabetes and cardiovascular diseases, its effects on
      type 2 diabetic nephropathy remain unknown. This study examined the
      renoprotective effects of DR in Wistar fatty (fa/fa) rats (WFRs). METHODS: WFRs
      were treated with DR (40% restriction) for 24 weeks. Urinary albumin excretion,
      creatinine clearance, renal histologies, acetylated-NF-kappaB (p65), Sirt1
      protein expression, and p62/Sqstm 1 accumulation in the renal cortex, as well as
      electron microscopic observation of mitochondrial morphology and autophagosomes
      in proximal tubular cells were estimated. RESULTS: DR ameliorated renal
      abnormalities including inflammation in WFRs. The decrease in Sirt1 levels,
      increase in acetylated-NF-kappaB, and impaired autophagy in WFRs were improved by
      DR. CONCLUSIONS: DR exerted anti-inflammatory effects and improved the
      dysregulation of autophagy through the restoration of Sirt1 in the kidneys of
      WFRs, which resulted in the amelioration of renal injuries in type 2 diabetes.

PMID- 21949663
TI  - The regenerating gene ialpha is overexpressed in atrophic gastritis rats with
      hypergastrinemia.
AB  - The role of gastrin on the development of atrophic gastritis (AG) and its
      relationship with the expression of RegIalpha  in vivo remain unclear. We
      established experimental AG in rats by combination administration with sodium
      salicylate, alcohol, and deoxycholate sodium. The mean score of inflammation in
      gastric antrum in AG rats was significantly elevated (P < 0.05), while the number
      of glands dramatically decreased (P < 0.05). In addition, the cell proliferation
      in gastric glands was increased in experimental AG rats, as determined by
      immunohistochemistry staining of PCNA and GS II. The level of serum gastrin in AG
      rats was significantly elevated relative to that of normal rats (P < 0.01).
      Moreover, the expression of RegIalpha protein and its receptor mRNA was increased
      in gastric tissues in AG rats (P < 0.05). Taken together, we demonstrated that
      the overexpression of Reglalpha is related with hypergastrinemia in AG rats.

PMID- 21949664
TI  - Effect of cavity configuration (C factor) on the marginal adaptation of low
      shrinking composite: a comparative ex vivo study.
AB  - Aim. To investigate the effect of C factor on marginal adaptation of low
      shrinking composite (Silorane).The null hypothesis was that the marginal
      adaptation of "Silorane" is not affected by the cavity configuration. Materials
      and Methods. A Silorane based and a methacrylate based composites, with their
      corresponding self-etch adhesive systems "Filtek Silorane/Silorane Adhesive Bond
      System and Filtek Z250/Prompt L-Pop" respectively were used. Standardized
      cavities were prepared on the buccal surfaces of 100 maxillary premolars. Teeth
      were grouped into 5 groups (n = 20), for the 5 C factors. Restored teeth were
      subjected to thermocycling. Microleakage testing was done and linear dye
      penetration was assessed using a stereomicroscope. Statistical analysis was done
      using the Student's t-test. Results. For the methacrylate based systems' overall
      leakage score was significantly higher than the Silorane-based one (P = 0.034).
      For the methacrylate-based, leakage was found in all tested teeth groups except
      group 1 (C factor 1/5). For the Silorane, One-way ANOVA revealed a statistically
      significant increase in dye penetration in the 5th group (P = 0.010).
      Conclusions. The null hypothesis was rejected. The Silorane-based resin although
      it resulted in a statistically significant good marginal adaptation, it showed
      tendency toward a high leakage score with C-factor of 5.

PMID- 21949665
TI  - Ambulatory pessary trial unmasks occult stress urinary incontinence.
AB  - Objective. We evaluated the use of a one-week ambulatory pessary trial in
      predicting patients' postoperative outcomes for occult stress incontinence.
      Methods. Patients with anterior vaginal wall prolapse were offered a pessary
      trial to predict response to reconstruction. We performed a retrospective review
      of 4 years of cases. All patients underwent a detailed evaluation including
      videourodynamics with and without pessary reduction. Results. Twenty-six patients
      completed the 1-week pessary trial. Ten (38%) women showing no evidence of stress
      urinary incontinence (SUI) underwent surgical repair of prolapse without anti
      incontinence procedure. None of these patients had SUI postoperatively. Sixteen
      women (61%) had occult stress urinary incontinence on evaluation and underwent
      concurrent sling procedure. Three (19%) of these patients were identified by the
      pessary trial alone. Twenty-five of the 26 patients were without clinical stress
      incontinence at a mean follow up of 12 months (range 4-37 months). The pessary
      trial correctly predicted persistent urgency in six patients and persistent
      frequency in five. No patients with SUI or persistent voiding difficult were
      missed in a pessary trial. Conclusion. An ambulatory pessary trial is an
      effective, easy, and inexpensive method to approximate anatomic results achieved
      by surgery under real-life conditions. In our series, 20% of patients with occult
      SUI were identified by pessary trial alone.

PMID- 21949666
TI  - Bipartite anterior extraperitoneal teratoma: evidence for the embryological
      origins of teratomas?
AB  - Teratomas are thought to arise from totipotent primordial germ cells (PGCs)
      Dehner (1983) which may miss their target destination Moore and Persaud (1984).
      Teratomas can occur anywhere from the brain to the coccygeal area but are usually
      in the midline close to the embryological position of the gonadal ridges Bale
      (1984), Nguyen and Laberge (2000). We report a case of a bipartite anterior
      extraperitoneal teratoma. This is an unusual position for a teratoma, but one
      which may support the "missed target" theory of embryology.

PMID- 21949669
TI  - Comparison of sasang constitutional medicine, traditional chinese medicine and
      ayurveda.
AB  - Sasang constitutional medicine (SCM), traditional Chinese medicine (TCM) and
      Ayurveda are three different forms of Asian traditional medicine. Although these
      traditions share a lot in common as holistic medicines, the different
      philosophical foundations found in each confer distinguishing attributes and
      unique qualities. SCM is based on a constitution-based approach, and is in this
      way relatively more similar to the Ayurvedic tradition than to the TCM, although
      many of the basic SCM theories were originally derived from TCM, a syndrome-based
      medicine. SCM and TCM use the same botanical materials that are distributed
      mainly in the East Asian region, but the basic principles of usage and the
      underlying rationale are completely different from each other. Meanwhile, the
      principles of the Ayurvedic use of botanical resources are very similar to those
      seen in SCM, but the medicinal herbs used in Ayurveda generally originate from
      the West Asian region which displays a different spectrum of flora.

PMID- 21949668
TI  - The role of the intestinal context in the generation of tolerance and
      inflammation.
AB  - The mucosal surface of the intestine alone forms the largest area exposed to
      exogenous antigens as well as the largest collection of lymphoid tissue in the
      body. The enormous amount of nonpathogenic and pathogenic bacteria and food
      derived antigens that we are daily exposed sets an interesting challenge to the
      immune system: a protective immune activity must coexist with efficient
      regulatory mechanisms in order to maintain a health status of these organisms.
      This paper discusses how the immune system assimilates the perturbations from the
      environment without generating tissue damage.

PMID- 21949667
TI  - Ghrelin, appetite regulation, and food reward: interaction with chronic stress.
AB  - Obesity has become one of the leading causes of illness and mortality in the
      developed world. Preclinical and clinical data provide compelling evidence for
      ghrelin as a relevant regulator of appetite, food intake, and energy homeostasis.
      In addition, ghrelin has recently emerged as one of the major contributing
      factors to reward-driven feeding that can override the state of satiation. The
      corticotropin-releasing-factor system is also directly implicated in the
      regulation of energy balance and may participate in the pathophysiology of
      obesity and eating disorders. This paper focuses on the role of ghrelin in the
      regulation of appetite, on its possible role as a hedonic signal involved in food
      reward, and on its interaction with the corticotropin-releasing-factor system and
      chronic stress.

PMID- 21949670
TI  - Aromatherapy massage on the abdomen for alleviating menstrual pain in high school
      girls: a preliminary controlled clinical study.
AB  - This study investigated the alleviating effects of aromatherapy massage and
      acetaminophen on menstrual pain in Korean high school girls. Subjects were
      divided into two groups: the aromatherapy massage (treatment) group (n = 32) and
      the acetaminophen (control) group (n = 23). Aromatherapy massage was performed on
      subjects in the treatment group. The abdomen was massaged once using clary sage,
      marjoram, cinnamon, ginger, and geranium in a base of almond oil. The level of
      menstrual pain was assessed using a visual analogue scale at baseline and twenty
      four hours afterward. The reduction of menstrual pain was significantly higher in
      the aromatherapy group than in the acetaminophen group. Using multiple
      regression, aromatherapy massage was found to be more highly associated with
      reduction in the level of menstrual pain than acetaminophen. These finding
      suggest that aromatherapy massage may be an effective treatment for menstrual
      pain in high school girls. However, it could not be verified whether the positive
      effects derived from the aromatherapy, the massage, or both. Further rigorous
      studies should be conducted using more objective measures.

PMID- 21949671
TI  - A new application for the optimal foraging theory: the extraction of medicinal
      plants.
AB  - The Optimal Foraging Theory was used to identify possible patterns in bark
      extraction and the selective cutting of Anadenanthera colubrina (Angico), a
      medicinal plant. The hypotheses were built on two approaches: selection of
      collection place and bark exploitation occurrence in only one of these resource
      areas. The results suggest that the distance that must be traveled to reach each
      gathering site determines the extent of the extraction process, showing that
      people minimize the time and energy spent in A. colubrina collection. The
      availability of each site appears not to influence the operation. The resource
      amount was the optimized variable for bark extraction, which was analyzed in only
      one collection zone. In contrast to the phenomenon of collection place selection,
      the distance between angico individuals, the management period, and the tannin
      content did not affect bark extraction. This study also discusses how certain
      cultural aspects influence the extraction of angico.

PMID- 21949672
TI  - The ten grand challenges of synthetic life.
AB  - The construction of artificial life is one of the main scientific challenges of
      the Synthetic Biology era. Advances in DNA synthesis and a better understanding
      of regulatory processes make the goal of constructing the first artificial cell a
      realistic possibility. This would be both a fundamental scientific milestone and
      a starting point of a vast range of applications, from biofuel production to drug
      design. However, several major issues might hamper the objective of achieving an
      artificial cell. From the bottom-up to the selection-based strategies, this work
      encompasses the ten grand challenges synthetic biologists will have to be aware
      of in order to cope with the task of creating life in the lab.

PMID- 21949673
TI  - Antigen-expressing immunostimulatory liposomes as a genetically programmable
      synthetic vaccine.
AB  - Liposomes are versatile (sub)micron-sized membrane vesicles that can be used for
      a variety of applications, including drug delivery and in vivo imaging but they
      also represent excellent models for artificial membranes or cells. Several
      studies have demonstrated that in vitro transcription and translation can take
      place inside liposomes to obtain compartmentalized production of functional
      proteins within the liposomes (Kita et al. in Chembiochem 9(15):2403-2410, 2008;
      Moritani et al.in FEBS J, 2010; Kuruma et al. in Methods Mol Biol 607:161-171,
      2010; Murtas et al. in Biochem Biophys Res Commun 363(1):12-17, 2007; Sunami et
      al. in Anal Biochem 357(1):128-136, 2006; Ishikawa et al. in FEBS Lett 576(3):387
      390, 2004; Oberholzer et al. in Biochem Biophys Res Commun 261(2):238-241, 1999).
      Such a minimal artificial cell-based model is ideal for synthetic biology based
      applications. In this study, we propose the use of liposomes as artificial
      microbes for vaccination. These artificial microbes can be genetically programmed
      to produce specific antigens at will. To show proof-of-concept for this
      artificial cell-based platform, a bacterial in vitro transcription and
      translation system together with a gene construct encoding the model antigen beta
      galactosidase were entrapped inside multilamellar liposomes. Vaccination studies
      in mice showed that such antigen-expressing immunostimulatory liposomes (AnExILs)
      elicited higher specific humoral immune responses against the produced antigen
      (beta-galactosidase) than control vaccines (i.e. AnExILs without genetic input,
      liposomal beta-galactosidase or pDNA encoding beta-galactosidase). In conclusion,
      AnExILs present a new platform for DNA-based vaccines which combines antigen
      production, adjuvanticity and delivery in one system and which offer several
      advantages over existing vaccine formulations.

PMID- 21949674
TI  - Dynamic modeling of gene expression in prokaryotes: application to glucose
      lactose diauxie in Escherichia coli.
AB  - Coexpression of genes or, more generally, similarity in the expression profiles
      poses an unsurmountable obstacle to inferring the gene regulatory network (GRN)
      based solely on data from DNA microarray time series. Clustering of genes with
      similar expression profiles allows for a course-grained view of the GRN and a
      probabilistic determination of the connectivity among the clusters. We present a
      model for the temporal evolution of a gene cluster network which takes into
      account interactions of gene products with genes and, through a non-constant
      degradation rate, with other gene products. The number of model parameters is
      reduced by using polynomial functions to interpolate temporal data points. In
      this manner, the task of parameter estimation is reduced to a system of linear
      algebraic equations, thus making the computation time shorter by orders of
      magnitude. To eliminate irrelevant networks, we test each GRN for stability with
      respect to parameter variations, and impose restrictions on its behavior near the
      steady state. We apply our model and methods to DNA microarray time series' data
      collected on Escherichia coli during glucose-lactose diauxie and infer the most
      probable cluster network for different phases of the experiment. ELECTRONIC
      SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11693
      011-9079-2) contains supplementary material, which is available to authorized
      users.

PMID- 21949675
TI  - The temporal dynamics of voluntary emotion regulation.
AB  - BACKGROUND: Neuroimaging has demonstrated that voluntary emotion regulation is
      effective in reducing amygdala activation to aversive stimuli during regulation.
      However, to date little is known about the sustainability of these neural effects
      once active emotion regulation has been terminated. METHODOLOGY/PRINCIPAL
      FINDINGS: We addressed this issue by means of functional magnetic resonance
      imaging (fMRI) in healthy female subjects. We performed an active emotion
      regulation task using aversive visual scenes (task 1) and a subsequent passive
      viewing task using the same stimuli (task 2). Here we demonstrate not only a
      significantly reduced amygdala activation during active regulation but also a
      sustained regulation effect on the amygdala in the subsequent passive viewing
      task. This effect was related to an immediate increase of amygdala signal in task
      1 once active emotion regulation has been terminated: The larger this peak
      postregulation signal in the amygdala in task 1, the smaller the sustained
      regulation effect in task 2. CONCLUSIONS/SIGNIFICANCE: In summary, we found clear
      evidence that effects of voluntary emotion regulation extend beyond the period of
      active regulation. These findings are of importance for the understanding of
      emotion regulation in general, for disorders of emotion regulation and for
      psychotherapeutic interventions.

PMID- 21949676
TI  - MACSE: Multiple Alignment of Coding SEquences accounting for frameshifts and stop
      codons.
AB  - Until now the most efficient solution to align nucleotide sequences containing
      open reading frames was to use indirect procedures that align amino acid
      translation before reporting the inferred gap positions at the codon level. There
      are two important pitfalls with this approach. Firstly, any premature stop codon
      impedes using such a strategy. Secondly, each sequence is translated with the
      same reading frame from beginning to end, so that the presence of a single
      additional nucleotide leads to both aberrant translation and alignment.We present
      an algorithm that has the same space and time complexity as the classical
      Needleman-Wunsch algorithm while accommodating sequencing errors and other
      biological deviations from the coding frame. The resulting pairwise coding
      sequence alignment method was extended to a multiple sequence alignment (MSA)
      algorithm implemented in a program called MACSE (Multiple Alignment of Coding
      SEquences accounting for frameshifts and stop codons). MACSE is the first
      automatic solution to align protein-coding gene datasets containing non
      functional sequences (pseudogenes) without disrupting the underlying codon
      structure. It has also proved useful in detecting undocumented frameshifts in
      public database sequences and in aligning next-generation sequencing
      reads/contigs against a reference coding sequence.MACSE is distributed as an open
      source java file executable with freely available source code and can be used via
      a web interface at: http://mbb.univ-montp2.fr/macse.

PMID- 21949677
TI  - Degradation of HIF-1alpha under hypoxia combined with induction of Hsp90
      polyubiquitination in cancer cells by hypericin: a unique cancer therapy.
AB  - The perihydroxylated perylene quinone hypericin has been reported to possess
      potent anti-metastatic and antiangiogenic activities, generated by targeting
      diverse crossroads of cancer-promoting processes via unique mechanisms. Hypericin
      is the only known exogenous reagent that can induce forced poly-ubiquitination
      and accelerated degradation of heat shock protein 90 (Hsp90) in cancer cells.
      Hsp90 client proteins are thereby destabilized and rapidly degraded. Hsp70 client
      proteins may potentially be also affected via preventing formation of hsp90-hsp70
      intermediate complexes. We show here that hypericin also induces enhanced
      degradation of hypoxia-inducible factor 1alpha (HIF-1alpha) in two human tumor
      cell lines, U87-MG glioblastoma and RCC-C2VHL-/- renal cell carcinoma and in the
      non-malignant ARPE19 retinal pigment epithelial cell line. The hypericin
      accelerated turnover of HIF-1alpha, the regulatory precursor of the HIF-1
      transcription factor which promotes hypoxic stress and angiogenic responses,
      overcomes the physiologic HIF-1alpha protein stabilization which occurs in
      hypoxic cells. The hypericin effect also eliminates the high HIF-1alpha levels
      expressed constitutively in the von-Hippel Lindau protein (pVHL)-deficient RCC
      C2VHL-/- renal cell carcinoma cell line. Unlike the normal ubiquitin-proteasome
      pathway-dependent turnover of HIF-alpha proteins which occurs in normoxia, the
      hypericin-induced HIF-1alpha catabolism can occur independently of cellular
      oxygen levels or pVHL-promoted ubiquitin ligation of HIF-1alpha. It is mediated
      by lysosomal cathepsin-B enzymes with cathepsin-B activity being optimized in the
      cells through hypericin-mediated reduction in intracellular pH. Our findings
      suggest that hypericin may potentially be useful in preventing growth of tumors
      in which HIF-1alpha plays pivotal roles, and in pVHL ablated tumor cells such as
      renal cell carcinoma through elimination of elevated HIF-1alpha contents in these
      cells, scaling down the excessive angiogenesis which characterizes these tumors.

PMID- 21949678
TI  - SLC37A1 and SLC37A2 are phosphate-linked, glucose-6-phosphate antiporters.
AB  - Blood glucose homeostasis between meals depends upon production of glucose within
      the endoplasmic reticulum (ER) of the liver and kidney by hydrolysis of glucose-6
      phosphate (G6P) into glucose and phosphate (P(i)). This reaction depends on
      coupling the G6P transporter (G6PT) with glucose-6-phosphatase-alpha (G6Pase
      alpha). Only one G6PT, also known as SLC37A4, has been characterized, and it acts
      as a P(i)-linked G6P antiporter. The other three SLC37 family members, predicted
      to be sugar-phosphate:P(i) exchangers, have not been characterized functionally.
      Using reconstituted proteoliposomes, we examine the antiporter activity of the
      other SLC37 members along with their ability to couple with G6Pase-alpha. G6PT-
      and mock-proteoliposomes are used as positive and negative controls,
      respectively. We show that SLC37A1 and SLC37A2 are ER-associated, P(i)-linked
      antiporters, that can transport G6P. Unlike G6PT, neither is sensitive to
      chlorogenic acid, a competitive inhibitor of physiological ER G6P transport, and
      neither couples to G6Pase-alpha. We conclude that three of the four SLC37 family
      members are functional sugar-phosphate antiporters. However, only G6PT/SLC37A4
      matches the characteristics of the physiological ER G6P transporter, suggesting
      the other SLC37 proteins have roles independent of blood glucose homeostasis.

PMID- 21949679
TI  - Erythrocyte and porcine intestinal glycosphingolipids recognized by F4 fimbriae
      of enterotoxigenic Escherichia coli.
AB  - Enterotoxigenic F4-fimbriated Escherichia coli is associated with diarrheal
      disease in neonatal and postweaning pigs. The F4 fimbriae mediate attachment of
      the bacteria to the pig intestinal epithelium, enabling an efficient delivery of
      diarrhea-inducing enterotoxins to the target epithelial cells. There are three
      variants of F4 fimbriae designated F4ab, F4ac and F4ad, respectively, having
      different antigenic and adhesive properties. In the present study, the binding of
      isolated F4ab, F4ac and F4ad fimbriae, and F4ab/ac/ad-fimbriated E. coli, to
      glycosphingolipids from erythrocytes and from porcine small intestinal epithelium
      was examined, in order to get a comprehensive view of the F4-binding
      glycosphingolipids involved in F4-mediated hemagglutination and adhesion to the
      epithelial cells of porcine intestine. Specific interactions between the F4ab,
      F4ac and F4ad fimbriae and both acid and non-acid glycosphingolipids were
      obtained, and after isolation of binding-active glycosphingolipids and
      characterization by mass spectrometry and proton NMR, distinct carbohydrate
      binding patterns were defined for each fimbrial subtype. Two novel
      glycosphingolipids were isolated from chicken erythrocytes, and characterized as
      GalNAcalpha3GalNAcbeta3Galbeta4Glcbeta1Cer and
      GalNAcalpha3GalNAcbeta3Galbeta4GlcNAcbeta3Galbeta4Glcbeta1Cer. These two
      compounds, and lactosylceramide (Galbeta4Glcbeta1Cer) with phytosphingosine and
      hydroxy fatty acid, were recognized by all three variants of F4 fimbriae. No
      binding of the F4ad fimbriae or F4ad-fimbriated E. coli to the porcine intestinal
      glycosphingolipids occurred. However, for F4ab and F4ac two distinct binding
      patterns were observed. The F4ac fimbriae and the F4ac-expressing E. coli
      selectively bound to galactosylceramide (Galbeta1Cer) with sphingosine and
      hydroxy 24:0 fatty acid, while the porcine intestinal glycosphingolipids
      recognized by F4ab fimbriae and the F4ab-fimbriated bacteria were characterized
      as galactosylceramide, sulfatide (SO(3)-3Galbeta1Cer), sulf-lactosylceramide
      (SO(3)-3Galbeta4Glcbeta1Cer), and globotriaosylceramide
      (Galalpha4Galbeta4Glcbeta1Cer) with phytosphingosine and hydroxy 24:0 fatty acid.
      Finally, the F4ad fimbriae and the F4ad-fimbriated E. coli, but not the F4ab or
      F4ac subtypes, bound to reference gangliotriaosylceramide
      (GalNAcbeta4Galbeta4Glcbeta1Cer), gangliotetraosylceramide
      (Galbeta3GalNAcbeta4Galbeta4Glcbeta1Cer), isoglobotriaosylceramide
      (Galalpha3Galbeta4Glcbeta1Cer), and neolactotetraosylceramide
      (Galbeta4GlcNAcbeta3Galbeta4Glcbeta1Cer).

PMID- 21949680
TI  - South American Plasmodium falciparum after the malaria eradication era: clonal
      population expansion and survival of the fittest hybrids.
AB  - Malaria has reemerged in many regions where once it was nearly eliminated. Yet
      the source of these parasites, the process of repopulation, their population
      structure, and dynamics are ill defined. Peru was one of malaria eradication's
      successes, where Plasmodium falciparum was nearly eliminated for two decades. It
      reemerged in the 1990s. In the new era of malaria elimination, Peruvian P.
      falciparum is a model of malaria reinvasion. We investigated its population
      structure and drug resistance profiles. We hypothesized that only populations
      adapted to local ecological niches could expand and repopulate and originated as
      vestigial populations or recent introductions. We investigated the genetic
      structure (using microsatellites) and drug resistant genotypes of 220 parasites
      collected from patients immediately after peak epidemic expansion (1999-2000)
      from seven sites across the country. The majority of parasites could be grouped
      into five clonal lineages by networks and AMOVA. The distribution of clonal
      lineages and their drug sensitivity profiles suggested geographic structure. In
      2001, artesunate combination therapy was introduced in Peru. We tested 62
      parasites collected in 2006-2007 for changes in genetic structure. Clonal
      lineages had recombined under selection for the fittest parasites. Our findings
      illustrate that local adaptations in the post-eradication era have contributed to
      clonal lineage expansion. Within the shifting confluence of drug policy and
      malaria incidence, populations continue to evolve through genetic outcrossing
      influenced by antimalarial selection pressure. Understanding the population
      substructure of P. falciparum has implications for vaccine, drug, and
      epidemiologic studies, including monitoring malaria during and after the
      elimination phase.

PMID- 21949681
TI  - Expression and function of osteopontin in vascular adventitial fibroblasts and
      pathological vascular remodeling.
AB  - Osteopontin is known to play important roles in various diseases including
      vascular disorders. However, little is known about its expression and function in
      vascular adventitial fibroblasts. Adventitial fibroblasts have been shown to play
      a key role in pathological vascular remodeling associating with various vascular
      disorders. In this study, we measured activation of Osteopontin and its
      biological functions in cultured adventitial fibroblasts and injured rat carotid
      injury arteries induced by balloon angioplasty. Our results showed that
      angiotensin II and aldosterone increased Osteopontin expression in adventitial
      fibroblasts in a time- and concentration-dependent manner. MAPKs and AP-1
      pathways were involved in Osteopontin upregulation. In addition, Adventitial
      fibroblast migration stimulated by Angiotensin II and aldosterone required OPN
      expression. Perivascular delivery of antisense oligonucleotide for Osteopontin
      suppressed neointimal formation post-injury. We concluded that upregulation of
      Osteopontin expression in adventitial fibroblasts might be important in the
      pathogenesis of vascular remodeling after arterial injury.

PMID- 21949682
TI  - P-glycoprotein dysfunction contributes to hepatic steatosis and obesity in mice.
AB  - Although the main role of P-glycoprotein (Pgp) is to extrude a broad range of
      xenochemicals and to protect the organism against xenotoxicity, it also
      transports a large range of endogenous lipids. Using mice lacking Pgp, we have
      investigated the possible involvement of Pgp in lipid homeostasis in vivo. In a
      long term study, we have followed the food intake, body status and lipid markers
      in plasma and liver of wild-type and mdr1ab(-/-) mice over 35 weeks. Pgp
      deficient mice showed excess weight, hypertrophy of adipose mass, high insulin
      and glucose levels in plasma. Some of these metabolic disruptions appeared
      earlier in Pgp-deficient mice fed high-fat diet. Moreover, hepatosteatosis with
      increased expression of genes involved in liver detoxification and in de novo
      lipid synthesis occurred in Pgp-deficient mice. Overall, Pgp deficiency clearly
      induced obesity in FVB genetic background, which is known to be resistant to diet
      induced obesity. These data reinforce the finding that Pgp gene could be a
      contributing factor and possibly a relevant marker for lipid disorder and
      obesity. Subsequent to Pgp deficiency, changes in body availabilities of lipids
      or any Pgp substrates may affect metabolic pathways that favour the occurrence of
      obesity. This is of special concern because people are often facing simultaneous
      exposition to many xenochemicals, which inhibits Pgp, and an excess in lipid
      dietary intake that may contribute to the high prevalence of obesity in our
      occidental societies.

PMID- 21949683
TI  - The ETS family member TEL binds to nuclear receptors RAR and RXR and represses
      gene activation.
AB  - Retinoic acid receptor (RAR) signaling is important for regulating
      transcriptional activity of genes involved in growth, differentiation, metabolism
      and reproduction. Defects in RAR signaling have been implicated in cancer. TEL, a
      member of the ETS family of transcription factors, is a DNA-binding
      transcriptional repressor. Here, we identify TEL as a transcriptional repressor
      of RAR signaling by its direct binding to both RAR and its dimerisation partner,
      the retinoid x receptor (RXR) in a ligand-independent fashion. TEL is found in
      two isoforms, created by the use of an alternative startcodon at amino acid 43.
      Although both isoforms bind to RAR and RXR in vitro and in vivo, the shorter form
      of TEL represses RAR signaling much more efficiently. Binding studies revealed
      that TEL binds closely to the DNA binding domain of RAR and that both Helix Loop
      Helix (HLH) and DNA binding domains of TEL are mandatory for interaction. We have
      shown that repression by TEL does not involve recruitment of histone deacetylases
      and suggest that polycomb group proteins participate in the process.

PMID- 21949684
TI  - Getting a head start: diet, sub-adult growth, and associative learning in a seed
      eating passerine.
AB  - Developmental stress, and individual variation in response to it, can have
      important fitness consequences. Here we investigated the consequences of variable
      dietary protein on the duration of growth and associative learning abilities of
      zebra finches, Taeniopygia guttata, which are obligate graminivores. The high
      protein conditions that zebra finches would experience in nature when half-ripe
      seed is available were mimicked by the use of egg protein to supplement mature
      seed, which is low in protein content. Growth rates and relative body proportions
      of males reared either on a low-protein diet (mature seed only) or a high-protein
      diet (seed plus egg) were determined from body size traits (mass, head width, and
      tarsus) measured at three developmental stages. Birds reared on the high-protein
      diet were larger in all size traits at all ages, but growth rates of size traits
      showed no treatment effects. Relative head size of birds reared on the two diets
      differed from age day 95 onward, with high-diet birds having larger heads in
      proportion to both tarsus length and body mass. High-diet birds mastered an
      associative learning task in fewer bouts than those reared on the low-protein
      diet. In both diet treatments, amount of sub-adult head growth varied directly,
      and sub-adult mass change varied inversely, with performance on the learning
      task. Results indicate that small differences in head growth during the sub-adult
      period can be associated with substantial differences in adult cognitive
      performance. Contrary to a previous report, we found no evidence for growth
      compensation among birds on the low-protein diet. These results have implications
      for the study of vertebrate cognition, developmental stress, and growth
      compensation.

PMID- 21949685
TI  - Secreted protein acidic and rich in cysteine is a matrix scavenger chaperone.
AB  - Secreted Protein Acidic and Rich in Cysteine (SPARC) is one of the major non
      structural proteins of the extracellular matrix (ECM) in remodeling tissues. The
      functional significance of SPARC is emphasized by its origin in the first
      multicellular organisms and its high degree of evolutionary conservation.
      Although SPARC has been shown to act as a critical modulator of ECM remodeling
      with profound effects on tissue physiology and architecture, no plausible
      molecular mechanism of its action has been proposed. In the present study, we
      demonstrate that SPARC mediates the disassembly and degradation of ECM networks
      by functioning as a matricellular chaperone. While it has low affinity to its
      targets inside the cells where the Ca(2+) concentrations are low, high
      extracellular concentrations of Ca(2+) activate binding to multiple ECM proteins,
      including collagens. We demonstrated that in vitro, this leads to the inhibition
      of collagen I fibrillogenesis and disassembly of pre-formed collagen I fibrils by
      SPARC at high Ca(2+) concentrations. In cell culture, exogenous SPARC was
      internalized by the fibroblast cells in a time- and concentration-dependent
      manner. Pulse-chase assay further revealed that internalized SPARC is quickly
      released outside the cell, demonstrating that SPARC shuttles between the cell and
      ECM. Fluorescently labeled collagen I, fibronectin, vitronectin, and laminin were
      co-internalized with SPARC by fibroblasts, and semi-quantitative Western blot
      showed that SPARC mediates internalization of collagen I. Using a novel 3
      dimensional model of fluorescent ECM networks pre-deposited by live fibroblasts,
      we demonstrated that degradation of ECM depends on the chaperone activity of
      SPARC. These results indicate that SPARC may represent a new class of scavenger
      chaperones, which mediate ECM degradation, remodeling and repair by disassembling
      ECM networks and shuttling ECM proteins into the cell. Further understanding of
      this mechanism may provide insight into the pathogenesis of matrix-associated
      disorders and lead to the novel treatment strategies.

PMID- 21949686
TI  - PS integrins and laminins: key regulators of cell migration during Drosophila
      embryogenesis.
AB  - During embryonic development, there are numerous cases where organ or tissue
      formation depends upon the migration of primordial cells. In the Drosophila
      embryo, the visceral mesoderm (vm) acts as a substrate for the migration of
      several cell populations of epithelial origin, including the endoderm, the
      trachea and the salivary glands. These migratory processes require both integrins
      and laminins. The current model is that alphaPS1betaPS (PS1) and/or
      alphaPS3betaPS (PS3) integrins are required in migrating cells, whereas
      alphaPS2betaPS (PS2) integrin is required in the vm, where it performs an as yet
      unidentified function. Here, we show that PS1 integrins are also required for the
      migration over the vm of cells of mesodermal origin, the caudal visceral mesoderm
      (CVM). These results support a model in which PS1 might have evolved to acquire
      the migratory function of integrins, irrespective of the origin of the tissue.
      This integrin function is highly specific and its specificity resides mainly in
      the extracellular domain. In addition, we have identified the Laminin alpha1,2
      trimer, as the key extracellular matrix (ECM) component regulating CVM migration.
      Furthermore, we show that, as it is the case in vertebrates, integrins, and
      specifically PS2, contributes to CVM movement by participating in the correct
      assembly of the ECM that serves as tracks for migration.

PMID- 21949687
TI  - The von Hippel-Lindau tumor suppressor protein promotes c-Cbl-independent poly
      ubiquitylation and degradation of the activated EGFR.
AB  - Somatic mutations or reduced expression of the von Hippel-Lindau (VHL) tumor
      suppressor occurs in the majority of the clear cell renal cell carcinoma (ccRCC)
      and is a causal factor for the pathogenesis of ccRCC. pVHL was reported to
      suppress the oncogenic activity of Epidermal Growth Factor Receptor (EGFR) by
      reducing the expression of the EGFR agonist TGF-alpha and by reducing the
      translation efficiency of EGFR itself. Furthermore, it was reported that pVHL
      down-regulates activated EGFR by promoting efficient lysosomal degradation of the
      receptor. These modes of negative regulation of EGFR by pVHL were dependent on
      Hypoxia Inducible Factor (HIF). In this study, we report that HIF was not the
      only factor stabilizing the activated EGFR in VHL-deficient ccRCC cells. Down
      regulation of endogenous HIF in these cells had little effect on the turnover
      rates of the activated EGFR. Furthermore, neither pretreatment with lysosomal
      inhibitors pretreatment nor down-regulation of c-Cbl, a major E3 ubiquitin ligase
      that targets the activated EGFR for lysosomal degradation, significantly
      increased the stabilities of EGFR in VHL-expressing ccRCC cells. In contrast,
      pretreatment with proteasomal inhibitors extended EGFR lifetime and led to
      similar EGFR half-lives in VHL-expressing and VHL-deficient ccRCC cells. Down
      regulation of c-Cbl in VHL-deficient ccRCC cells revealed that the c-Cbl and pVHL
      collaborated to down-regulate the activated EGFR. Finally, we found that pVHL
      promoted the poly-ubiquitylation of the activated EGFR, and this function was c
      Cbl-independent. Thus these results indicate that pVHL limits EGFR signaling by
      promoting c-Cbl-independent poly-ubiquitylation of the activated receptor, which
      likely results in its degradation by proteasome.

PMID- 21949688
TI  - DRhoGEF2 regulates cellular tension and cell pulsations in the Amnioserosa during
      Drosophila dorsal closure.
AB  - Coordination of apical constriction in epithelial sheets is a fundamental process
      during embryogenesis. Here, we show that DRhoGEF2 is a key regulator of apical
      pulsation and constriction of amnioserosal cells during Drosophila dorsal
      closure. Amnioserosal cells mutant for DRhoGEF2 exhibit a consistent decrease in
      amnioserosa pulsations whereas overexpression of DRhoGEF2 in this tissue leads to
      an increase in the contraction time of pulsations. We probed the physical
      properties of the amnioserosa to show that the average tension in DRhoGEF2 mutant
      cells is lower than wild-type and that overexpression of DRhoGEF2 results in a
      tissue that is more solid-like than wild-type. We also observe that in the
      DRhoGEF2 overexpressing cells there is a dramatic increase of apical actomyosin
      coalescence that can contribute to the generation of more contractile forces,
      leading to amnioserosal cells with smaller apical surface than wild-type.
      Conversely, in DRhoGEF2 mutants, the apical actomyosin coalescence is impaired.
      These results identify DRhoGEF2 as an upstream regulator of the actomyosin
      contractile machinery that drives amnioserosa cells pulsations and apical
      constriction.

PMID- 21949689
TI  - The Later Stone Age calvaria from Iwo Eleru, Nigeria: morphology and chronology.
AB  - BACKGROUND: In recent years the Later Stone Age has been redated to a much deeper
      time depth than previously thought. At the same time, human remains from this
      time period are scarce in Africa, and even rarer in West Africa. The Iwo Eleru
      burial is one of the few human skeletal remains associated with Later Stone Age
      artifacts in that region with a proposed Pleistocene date. We undertook a
      morphometric reanalysis of this cranium in order to better assess its affinities.
      We also conducted Uranium-series dating to re-evaluate its chronology.
      METHODOLOGY/PRINCIPAL FINDINGS: A 3-D geometric morphometric analysis of cranial
      landmarks and semilandmarks was conducted using a large comparative fossil and
      modern human sample. The measurements were collected in the form of three
      dimensional coordinates and processed using Generalized Procrustes Analysis.
      Principal components, canonical variates, Mahalanobis D(2) and Procrustes
      distance analyses were performed. The results were further visualized by
      comparing specimen and mean configurations. Results point to a morphological
      similarity with late archaic African specimens dating to the Late Pleistocene. A
      long bone cortical fragment was made available for U-series analysis in order to
      re-date the specimen. The results (~11.7-16.3 ka) support a terminal Pleistocene
      chronology for the Iwo Eleru burial as was also suggested by the original
      radiocarbon dating results and by stratigraphic evidence.
      CONCLUSIONS/SIGNIFICANCE: Our findings are in accordance with suggestions of deep
      population substructure in Africa and a complex evolutionary process for the
      origin of modern humans. They further highlight the dearth of hominin finds from
      West Africa, and underscore our real lack of knowledge of human evolution in that
      region.

PMID- 21949690
TI  - A blueberry-enriched diet attenuates nephropathy in a rat model of hypertension
      via reduction in oxidative stress.
AB  - OBJECTIVE AND BACKGROUND: To assess renoprotective effects of a blueberry
      enriched diet in a rat model of hypertension. Oxidative stress (OS) appears to be
      involved in the development of hypertension and related renal injury.
      Pharmacological antioxidants can attenuate hypertension and hypertension-induced
      renal injury; however, attention has shifted recently to the therapeutic
      potential of natural products as antioxidants. Blueberries (BB) have among the
      highest antioxidant capacities of fruits and vegetables. METHODS AND RESULTS:
      Male spontaneously hypertensive rats received a BB-enriched diet (2% w/w) or an
      isocaloric control diet for 6 or 12 weeks or 2 days. Compared to controls, rats
      fed BB-enriched diet for 6 or 12 weeks exhibited lower blood pressure, improved
      glomerular filtration rate, and decreased renovascular resistance. As measured by
      electron paramagnetic resonance spectroscopy, significant decreases in total
      reactive oxygen species (ROS), peroxynitrite, and superoxide production rates
      were observed in kidney tissues in rats on long-term dietary treatment,
      consistent with reduced pathology and improved function. Additionally, measures
      of antioxidant status improved; specifically, renal glutathione and catalase
      activities increased markedly. Contrasted to these observations indicating
      reduced OS in the BB group after long-term feeding, similar measurements made in
      rats fed the same diet for only 2 days yielded evidence of increased OS;
      specifically, significant increases in total ROS, peroxynitrite, and superoxide
      production rates in all tissues (kidney, brain, and liver) assayed in BB-fed
      rats. These results were evidence of "hormesis" during brief exposure, which
      dissipated with time as indicated by enhanced levels of catalase in heart and
      liver of BB group. CONCLUSION: Long-term feeding of BB-enriched diet lowered
      blood pressure, preserved renal hemodynamics, and improved redox status in
      kidneys of hypertensive rats and concomitantly demonstrated the potential to
      delay or attenuate development of hypertension-induced renal injury, and these
      effects appear to be mediated by a short-term hormetic response.

PMID- 21949691
TI  - Suppression of inflammatory immune responses in celiac disease by experimental
      hookworm infection.
AB  - We present immunological data from two clinical trials where the effect of
      experimental human hookworm (Necator americanus) infection on the pathology of
      celiac disease was evaluated. We found that basal production of Interferon- (IFN
      )gamma and Interleukin- (IL-)17A from duodenal biopsy culture was suppressed in
      hookworm-infected participants compared to uninfected controls. Increased levels
      of CD4+CD25+Foxp3+ cells in the circulation and mucosa are associated with active
      celiac disease. We show that this accumulation also occurs during a short-term (1
      week) oral gluten challenge, and that hookworm infection suppressed the increase
      of circulating CD4+CD25+Foxp3+ cells during this challenge period. When duodenal
      biopsies from hookworm-infected participants were restimulated with the
      immunodominant gliadin peptide QE65, robust production of IL-2, IFN-gamma and IL
      17A was detected, even prior to gluten challenge while participants were strictly
      adhering to a gluten-free diet. Intriguingly, IL-5 was produced only after
      hookworm infection in response to QE65. Thus we hypothesise that hookworm-induced
      TH2 and IL-10 cross-regulation of the TH1/TH17 inflammatory response may be
      responsible for the suppression of these responses during experimental hookworm
      infection.

PMID- 21949692
TI  - Efficient elimination of cancer cells by deoxyglucose-ABT-263/737 combination
      therapy.
AB  - As single agents, ABT-263 and ABT-737 (ABT), molecular antagonists of the Bcl-2
      family, bind tightly to Bcl-2, Bcl-xL and Bcl-w, but not to Mcl-1, and induce
      apoptosis only in limited cell types. The compound 2-deoxyglucose (2DG), in
      contrast, partially blocks glycolysis, slowing cell growth but rarely causing
      cell death. Injected into an animal, 2DG accumulates predominantly in tumors but
      does not harm other tissues. However, when cells that were highly resistant to
      ABT were pre-treated with 2DG for 3 hours, ABT became a potent inducer of
      apoptosis, rapidly releasing cytochrome c from the mitochondria and activating
      caspases at submicromolar concentrations in a Bak/Bax-dependent manner. Bak is
      normally sequestered in complexes with Mcl-1 and Bcl-xL. 2DG primes cells by
      interfering with Bak-Mcl-1 association, making it easier for ABT to dissociate
      Bak from Bcl-xL, freeing Bak to induce apoptosis. A highly active glucose
      transporter and Bid, as an agent of the mitochondrial apoptotic signal
      amplification loop, are necessary for efficient apoptosis induction in this
      system. This combination treatment of cancer-bearing mice was very effective
      against tumor xenograft from hormone-independent highly metastasized chemo
      resistant human prostate cancer cells, suggesting that the combination treatment
      may provide a safe and effective alternative to genotoxin-based cancer therapies.

PMID- 21949693
TI  - The impairment of ILK related angiogenesis involved in cardiac maladaptation
      after infarction.
AB  - BACKGROUND: Integrin linked kinase (ILK), as an important component of mechanical
      stretch sensor, can initiate cellular signaling response in the heart when
      cardiac preload increases. Previous work demonstrated increased ILK expression
      could induce angiogenesis to improved heart function after MI. However the
      patholo-physiological role of ILK in cardiac remodeling after MI is not clear.
      METHOD AND RESULTS: Hearts were induced to cardiac remodeling by infarction and
      studied in Sprague-Dawley rats. Until 4 weeks after infarction, ILK expression
      was increased in non-ischemic tissue in parallel with myocytes hypertrophy and
      compensatory cardiac function. 8 weeks later, when decompensation of heart
      function occurred, ILK level returned to baseline. Followed ILK alternation,
      vascular endothelial growth factor (VEGF) expression and phosphorylation of
      endothelial nitric oxide synthase (eNOS) was significantly decreased 8 weeks
      after MI. Histology study also showed significantly microvessel decreased and
      myocytes loss 8 weeks paralleled with ILK down-regulation. While ILK expression
      was maintained by gene delivery, tissue angiogenesis and cardiac function was
      preserved during cardiac remodeling. CONCLUSION: Temporally up-regulation of ILK
      level in non-ischemic myocytes by increased external load is associated with
      beneficial angiogenesis to maintain infarction-induced cardiac hypertrophy. When
      ILK expression returns to normal, this cardiac adaptive response for infarction
      is weaken. Understanding the ILK related mechanism of cardiac maladaptation leads
      to a new strategy for treatment of heart failure after infarction.

PMID- 21949694
TI  - Critical period of nonpromoter DNA methylation acquisition during prenatal male
      germ cell development.
AB  - The prenatal period of germ cell development is a key time of epigenetic
      programming in the male, a window of development that has been shown to be
      influenced by maternal factors such as dietary methyl donor supply. DNA
      methylation occurring outside of promoter regions differs significantly between
      sperm and somatic tissues and has recently been linked with the regulation of
      gene expression during development as well as successful germline development. We
      examined DNA methylation at nonpromoter, intergenic sequences in purified
      prenatal and postnatal germ cells isolated from wildtype mice and mice deficient
      in the DNA methyltransferase cofactor DNMT3L. Erasure of the parental DNA
      methylation pattern occurred by 13.5 days post coitum (dpc) with the exception of
      approximately 8% of loci demonstrating incomplete erasure. For most loci, DNA
      methylation acquisition occurred between embryonic day 13.5 to 16.5 indicating
      that the key phase of epigenetic pattern establishment for intergenic sequences
      in male germ cells occurs prior to birth. In DNMT3L-deficient germ cells at 16.5
      dpc, average DNA methylation levels were low, about 30% of wildtype levels;
      however, by postnatal day 6, about half of the DNMT3L deficiency-specific
      hypomethylated loci had acquired normal methylation levels. Those loci normally
      methylated earliest in the prenatal period were the least affected in the DNMT3L
      deficient mice, suggesting that some loci may be more susceptible than others to
      perturbations occurring prenatally. These results indicate that the critical
      period of DNA methylation programming of nonpromoter, intergenic sequences occurs
      in male germline progenitor cells in the prenatal period, a time when external
      perturbations of epigenetic patterns could result in diminished fertility.

PMID- 21949695
TI  - Large-scale bi-level strain design approaches and mixed-integer programming
      solution techniques.
AB  - The use of computational models in metabolic engineering has been increasing as
      more genome-scale metabolic models and computational approaches become available.
      Various computational approaches have been developed to predict how genetic
      perturbations affect metabolic behavior at a systems level, and have been
      successfully used to engineer microbial strains with improved primary or
      secondary metabolite production. However, identification of metabolic engineering
      strategies involving a large number of perturbations is currently limited by
      computational resources due to the size of genome-scale models and the
      combinatorial nature of the problem. In this study, we present (i) two new bi
      level strain design approaches using mixed-integer programming (MIP), and (ii)
      general solution techniques that improve the performance of MIP-based bi-level
      approaches. The first approach (SimOptStrain) simultaneously considers gene
      deletion and non-native reaction addition, while the second approach (BiMOMA)
      uses minimization of metabolic adjustment to predict knockout behavior in a MIP
      based bi-level problem for the first time. Our general MIP solution techniques
      significantly reduced the CPU times needed to find optimal strategies when
      applied to an existing strain design approach (OptORF) (e.g., from ~10 days to ~5
      minutes for metabolic engineering strategies with 4 gene deletions), and
      identified strategies for producing compounds where previous studies could not
      (e.g., malate and serine). Additionally, we found novel strategies using
      SimOptStrain with higher predicted production levels (for succinate and glycerol)
      than could have been found using an existing approach that considers network
      additions and deletions in sequential steps rather than simultaneously. Finally,
      using BiMOMA we found novel strategies involving large numbers of modifications
      (for pyruvate and glutamate), which sequential search and genetic algorithms were
      unable to find. The approaches and solution techniques developed here will
      facilitate the strain design process and extend the scope of its application to
      metabolic engineering.

PMID- 21949696
TI  - Early embryonic vascular patterning by matrix-mediated paracrine signalling: a
      mathematical model study.
AB  - During embryonic vasculogenesis, endothelial precursor cells of mesodermal origin
      known as angioblasts assemble into a characteristic network pattern. Although a
      considerable amount of markers and signals involved in this process have been
      identified, the mechanisms underlying the coalescence of angioblasts into this
      reticular pattern remain unclear. Various recent studies hypothesize that
      autocrine regulation of the chemoattractant vascular endothelial growth factor
      (VEGF) is responsible for the formation of vascular networks in vitro. However,
      the autocrine regulation hypothesis does not fit well with reported data on in
      vivo early vascular development. In this study, we propose a mathematical model
      based on the alternative assumption that endodermal VEGF signalling activity,
      having a paracrine effect on adjacent angioblasts, is mediated by its binding to
      the extracellular matrix (ECM). Detailed morphometric analysis of simulated
      networks and images obtained from in vivo quail embryos reveals the model mimics
      the vascular patterns with high accuracy. These results show that paracrine
      signalling can result in the formation of fine-grained cellular networks when
      mediated by angioblast-produced ECM. This lends additional support to the theory
      that patterning during early vascular development in the vertebrate embryo is
      regulated by paracrine signalling.

PMID- 21949697
TI  - Characterisation of genome-wide PLZF/RARA target genes.
AB  - The PLZF/RARA fusion protein generated by the t(11;17)(q23;q21) translocation in
      acute promyelocytic leukaemia (APL) is believed to act as an oncogenic
      transcriptional regulator recruiting epigenetic factors to genes important for
      its transforming potential. However, molecular mechanisms associated with
      PLZF/RARA-dependent leukaemogenesis still remain unclear.We searched for specific
      PLZF/RARA target genes by ChIP-on-chip in the haematopoietic cell line U937
      conditionally expressing PLZF/RARA. By comparing bound regions found in U937
      cells expressing endogenous PLZF with PLZF/RARA-induced U937 cells, we isolated
      specific PLZF/RARA target gene promoters. We next analysed gene expression
      profiles of our identified target genes in PLZF/RARA APL patients and analysed
      DNA sequences and epigenetic modification at PLZF/RARA binding sites. We identify
      413 specific PLZF/RARA target genes including a number encoding transcription
      factors involved in the regulation of haematopoiesis. Among these genes, 22 were
      significantly down regulated in primary PLZF/RARA APL cells. In addition,
      repressed PLZF/RARA target genes were associated with increased levels of
      H3K27me3 and decreased levels of H3K9K14ac. Finally, sequence analysis of
      PLZF/RARA bound sequences reveals the presence of both consensus and degenerated
      RAREs as well as enrichment for tissue-specific transcription factor motifs,
      highlighting the complexity of targeting fusion protein to chromatin. Our study
      suggests that PLZF/RARA directly targets genes important for haematopoietic
      development and supports the notion that PLZF/RARA acts mainly as an epigenetic
      regulator of its direct target genes.

PMID- 21949698
TI  - Food supply and seawater pCO2 impact calcification and internal shell dissolution
      in the blue mussel Mytilus edulis.
AB  - Progressive ocean acidification due to anthropogenic CO(2) emissions will alter
      marine ecosystem processes. Calcifying organisms might be particularly vulnerable
      to these alterations in the speciation of the marine carbonate system. While
      previous research efforts have mainly focused on external dissolution of shells
      in seawater under saturated with respect to calcium carbonate, the internal shell
      interface might be more vulnerable to acidification. In the case of the blue
      mussel Mytilus edulis, high body fluid pCO(2) causes low pH and low carbonate
      concentrations in the extrapallial fluid, which is in direct contact with the
      inner shell surface. In order to test whether elevated seawater pCO(2) impacts
      calcification and inner shell surface integrity we exposed Baltic M. edulis to
      four different seawater pCO(2) (39, 142, 240, 405 Pa) and two food algae (310-350
      cells mL(-1) vs. 1600-2000 cells mL(-1)) concentrations for a period of seven
      weeks during winter (5 degrees C). We found that low food algae concentrations
      and high pCO(2) values each significantly decreased shell length growth. Internal
      shell surface corrosion of nacreous ( = aragonite) layers was documented via
      stereomicroscopy and SEM at the two highest pCO(2) treatments in the high food
      group, while it was found in all treatments in the low food group. Both factors,
      food and pCO(2), significantly influenced the magnitude of inner shell surface
      dissolution. Our findings illustrate for the first time that integrity of inner
      shell surfaces is tightly coupled to the animals' energy budget under conditions
      of CO(2) stress. It is likely that under food limited conditions, energy is
      allocated to more vital processes (e.g. somatic mass maintenance) instead of
      shell conservation. It is evident from our results that mussels exert significant
      biological control over the structural integrity of their inner shell surfaces.

PMID- 21949699
TI  - A double-blind randomized phase I clinical trial targeting ALVAC-HIV vaccine to
      human dendritic cells.
AB  - BACKGROUND: We conducted a novel pilot study comparing different delivery routes
      of ALVAC-HIV (vCP205), a canarypox vaccine containing HIV gene inserts: env, gag
      and pol. We explored the concept that direct ex vivo targeting of human dendritic
      cells (DC) would enhance the immune response compared to either conventional
      intramuscular or intradermal injections of the vaccine alone.
      METHODOLOGY/PRINCIPAL FINDINGS: Healthy HIV-1 uninfected volunteers were
      administered ALVAC-HIV or placebo by intramuscular injection (i.m.), intradermal
      injection (i.d.) or subcutaneous injection (s.q.) of autologous ex vivo
      transfected DC at months 0, 1, 3 and 6. All vaccine delivery routes were well
      tolerated. Binding antibodies were observed to both the ALVAC vector and HIV-1
      gp160 proteins. Modest cellular responses were observed in 2/7 individuals in the
      DC arm and 1/8 in the i.m. arm as determined by IFN-gamma ELISPOT. Proliferative
      responses were most frequent in the DC arm where 4/7 individuals had measurable
      responses to multiple HIV-1 antigens. Loading DC after maturation resulted in
      lower gene expression, but overall better responses to both HIV-1 and control
      antigens, and were associated with better IL-2, TNF-alpha and IFN-gamma
      production. CONCLUSIONS/SIGNIFICANCE: ALVAC-HIV delivered i.m., i.d. or s.q. with
      autologous ex vivo transfected DC proved to be safe. The DC arm was most
      immunogenic. Proliferative immune responses were readily detected with only
      modest cytotoxic CD8 T cell responses. Loading mature DC with the live viral
      vaccine induced stronger immune responses than loading immature DC, despite
      increased transgene expression with the latter approach. Volunteers who received
      the autologous vaccine loaded mature DC developed a broader and durable immune
      response compared to those vaccinated by conventional routes. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT00013572.

PMID- 21949701
TI  - Functional analysis beyond enrichment: non-redundant reciprocal linkage of genes
      and biological terms.
AB  - Functional analysis of large sets of genes and proteins is becoming more and more
      necessary with the increase of experimental biomolecular data at omic-scale.
      Enrichment analysis is by far the most popular available methodology to derive
      functional implications of sets of cooperating genes. The problem with these
      techniques relies in the redundancy of resulting information, that in most cases
      generate lots of trivial results with high risk to mask the reality of key
      biological events. We present and describe a computational method, called
      GeneTerm Linker, that filters and links enriched output data identifying sets of
      associated genes and terms, producing metagroups of coherent biological
      significance. The method uses fuzzy reciprocal linkage between genes and terms to
      unravel their functional convergence and associations. The algorithm is tested
      with a small set of well known interacting proteins from yeast and with a large
      collection of reference sets from three heterogeneous resources: multiprotein
      complexes (CORUM), cellular pathways (SGD) and human diseases (OMIM). Statistical
      Precision, Recall and balanced F-score are calculated showing robust results,
      even when different levels of random noise are included in the test sets.
      Although we could not find an equivalent method, we present a comparative
      analysis with a widely used method that combines enrichment and functional
      annotation clustering. A web application to use the method here proposed is
      provided at http://gtlinker.cnb.csic.es.

PMID- 21949700
TI  - Reversible plasticity of fear memory-encoding amygdala synaptic circuits even
      after fear memory consolidation.
AB  - It is generally believed that after memory consolidation, memory-encoding
      synaptic circuits are persistently modified and become less plastic. This,
      however, may hinder the remaining capacity of information storage in a given
      neural circuit. Here we consider the hypothesis that memory-encoding synaptic
      circuits still retain reversible plasticity even after memory consolidation. To
      test this, we employed a protocol of auditory fear conditioning which recruited
      the vast majority of the thalamic input synaptic circuit to the lateral amygdala
      (T-LA synaptic circuit; a storage site for fear memory) with fear conditioning
      induced synaptic plasticity. Subsequently the fear memory-encoding synaptic
      circuits were challenged with fear extinction and re-conditioning to determine
      whether these circuits exhibit reversible plasticity. We found that fear memory
      encoding T-LA synaptic circuit exhibited dynamic efficacy changes in tight
      correlation with fear memory strength even after fear memory consolidation.
      Initial conditioning or re-conditioning brought T-LA synaptic circuit near the
      ceiling of their modification range (occluding LTP and enhancing depotentiation
      in brain slices prepared from conditioned or re-conditioned rats), while
      extinction reversed this change (reinstating LTP and occluding depotentiation in
      brain slices prepared from extinguished rats). Consistently, fear conditioning
      induced synaptic potentiation at T-LA synapses was functionally reversed by
      extinction and reinstated by subsequent re-conditioning. These results suggest
      reversible plasticity of fear memory-encoding circuits even after fear memory
      consolidation. This reversible plasticity of memory-encoding synapses may be
      involved in updating the contents of original memory even after memory
      consolidation.

PMID- 21949702
TI  - PTPN22 1858C>T polymorphism distribution in Europe and association with
      rheumatoid arthritis: case-control study and meta-analysis.
AB  - OBJECTIVE: The PTPN22 rs2476601 polymorphism is associated with rheumatoid
      arthritis (RA); nonetheless, the association is weaker or absent in some southern
      European populations. The aim of the study was to evaluate the association
      between the PTPN22 rs2476601 polymorphism and RA in Italian subjects and to
      compare our results with those of other European countries, carrying out a meta
      analysis of European data. METHODS: A total of 396 RA cases and 477 controls, all
      of Italic ancestry, were genotyped for PTPN22 rs2476601 polymorphism. Patients
      were tested for autoantibodies positivity. The meta-analysis was performed on 23
      selected studies. RESULTS: The PTPN22 T1858 allele was significantly more
      frequent in RA patients compared to controls (5.7% vs. 3.7%, p = 0.045). No clear
      relationship arose with the autoantibodies tested. The 1858T allele frequency in
      Italian RA patients was lower than the one described in northern European
      populations and similar to the frequency found in Spain, Turkey, Greece, Tunisia.
      A clear-cut North-South gradient arose from the analysis. CONCLUSIONS: The PTPN22
      T1858 allele is associated with RA in the Italian population. A North-South
      gradient of the allele frequency seems to exist in Europe, with a lower
      prevalence of the mutation in the Mediterranean area.

PMID- 21949703
TI  - Cellular scale anisotropic topography guides Schwann cell motility.
AB  - Directed migration of Schwann cells (SC) is critical for development and repair
      of the peripheral nervous system. Understanding aspects of motility specific to
      SC, along with SC response to engineered biomaterials, may inform strategies to
      enhance nerve regeneration. Rat SC were cultured on laminin-coated microgrooved
      poly(dimethyl siloxane) platforms that were flat or presented repeating cellular
      scale anisotropic topographical cues, 30 or 60 um in width, and observed with
      timelapse microscopy. SC motion was directed parallel to the long axis of the
      topography on both the groove floor and the plateau, with accompanying
      differences in velocity and directional persistence in comparison to SC motion on
      flat substrates. In addition, feature dimension affected SC morphology,
      alignment, and directional persistence. Plateaus and groove floors presented
      distinct cues which promoted differential motility and variable interaction with
      the topographical features. SC on the plateau surfaces tended to have persistent
      interactions with the edge topography, while SC on the groove floors tended to
      have infrequent contact with the corners and walls. Our observations suggest the
      capacity of SC to be guided without continuous contact with a topographical cue.
      SC exhibited a range of distinct motile morphologies, characterized by their
      symmetry and number of extensions. Across all conditions, SC with a single
      extension traveled significantly faster than cells with more or no extensions. We
      conclude that SC motility is complex, where persistent motion requires cellular
      asymmetry, and that anisotropic topography with cellular scale features can
      direct SC motility.

PMID- 21949704
TI  - High burden of prevalent and recently acquired HIV among female sex workers and
      female HIV voluntary testing center clients in Kigali, Rwanda.
AB  - OBJECTIVES: To estimate HIV prevalence and risk factors in population-based
      samples of female sex workers (FSW) and female voluntary counseling and testing
      (VCT) clients in Rwanda. METHODS: We conducted a cross-sectional survey of 800
      FSW and 1,250 female VCT clients in Rwanda, which included interviewing and
      testing for HIV-1/2, HSV-2 and pregnancy, and BED-CEIA and Avidity Index (AI) to
      identify recent infections among HIV-infected women. RESULTS: Prevalence of HIV
      1, HSV-2, and pregnancy were 24% (95% CI: 21.0-27.0), 59.8% (56.4-63.2), and 7.6%
      (5.8-9.5) among FSW, and 12.8% (10.9-14.6), 43.2% (40.4-46.0), and 11.4% (9.7
      13.3) among VCT clients, respectively. Thirty-five percent of FSW and 25% of VCT
      clients had never been HIV tested. Per national guidelines, 33% of newly HIV
      diagnosed FSW and 36% of VCT clients were already eligible for ART based on
      CD4<350 cells/ul. Condom use at last sex was higher among FSW (74%) than VCT
      clients (12%). In age and district of residence-adjusted models, HIV-1
      seropositivity was associated with HSV-2 co-infection; recent treatment for
      sexually transmitted infection (STI); genital symptoms; forced sex; imprisonment;
      widowhood; and alcohol consumption. Eleven percent of FSW and 12% of VCT clients
      had recently acquired HIV-1 per BED-CEIA and AI. HSV-2 infection and recent STI
      treatment were associated with recent HIV infection in both groups, and being
      married and vaginal cleansing were associated with recent infection before last
      sex among VCT clients. CONCLUSIONS: This population-based survey reveals a high
      HIV prevalence and incidence among FSW and female VCT clients in Kigali, the
      scale of which is masked by the low general-population HIV prevalence in Rwanda.
      HIV/STI and family planning services should be strengthened.

PMID- 21949705
TI  - Cognitive and emotional alterations are related to hippocampal inflammation in a
      mouse model of metabolic syndrome.
AB  - Converging clinical data suggest that peripheral inflammation is likely involved
      in the pathogenesis of the neuropsychiatric symptoms associated with metabolic
      syndrome (MetS). However, the question arises as to whether the increased
      prevalence of behavioral alterations in MetS is also associated with central
      inflammation, i.e. cytokine activation, in brain areas particularly involved in
      controlling behavior. To answer this question, we measured in a mouse model of
      MetS, namely the diabetic and obese db/db mice, and in their healthy db/+
      littermates emotional behaviors and memory performances, as well as plasma levels
      and brain expression (hippocampus; hypothalamus) of inflammatory cytokines. Our
      results shows that db/db mice displayed increased anxiety-like behaviors in the
      open-field and the elevated plus-maze (i.e. reduced percent of time spent in
      anxiogenic areas of each device), but not depressive-like behaviors as assessed
      by immobility time in the forced swim and tail suspension tests. Moreover, db/db
      mice displayed impaired spatial recognition memory (hippocampus-dependent task),
      but unaltered object recognition memory (hippocampus-independent task). In
      agreement with the well-established role of the hippocampus in anxiety-like
      behavior and spatial memory, behavioral alterations of db/db mice were associated
      with increased inflammatory cytokines (interleukin-1beta, tumor necrosis factor
      alpha and interleukin-6) and reduced expression of brain-derived neurotrophic
      factor (BDNF) in the hippocampus but not the hypothalamus. These results strongly
      point to interactions between cytokines and central processes involving the
      hippocampus as important contributing factor to the behavioral alterations of
      db/db mice. These findings may prove valuable for introducing novel approaches to
      treat neuropsychiatric complications associated with MetS.

PMID- 21949706
TI  - Change and aging senescence as an adaptation.
AB  - Understanding why we age is a long-lived open problem in evolutionary biology.
      Aging is prejudicial to the individual, and evolutionary forces should prevent
      it, but many species show signs of senescence as individuals age. Here, I will
      propose a model for aging based on assumptions that are compatible with
      evolutionary theory: i) competition is between individuals; ii) there is some
      degree of locality, so quite often competition will be between parents and their
      progeny; iii) optimal conditions are not stationary, and mutation helps each
      species to keep competitive. When conditions change, a senescent species can
      drive immortal competitors to extinction. This counter-intuitive result arises
      from the pruning caused by the death of elder individuals. When there is change
      and mutation, each generation is slightly better adapted to the new conditions,
      but some older individuals survive by chance. Senescence can eliminate those from
      the genetic pool. Even though individual selection forces can sometimes win over
      group selection ones, it is not exactly the individual that is selected but its
      lineage. While senescence damages the individuals and has an evolutionary cost,
      it has a benefit of its own. It allows each lineage to adapt faster to changing
      conditions. We age because the world changes.

PMID- 21949707
TI  - Methicillin-resistant Staphylococcus aureus infection and hospitalization in high
      risk patients in the year following detection.
AB  - BACKGROUND: Many studies have evaluated methicillin-resistant Staphylococcus
      aureus (MRSA) infections during single hospitalizations and subsequent
      readmissions to the same institution. None have assessed the comprehensive burden
      of MRSA infection in the period after hospital discharge while accounting for
      healthcare utilization across institutions. METHODOLOGY/PRINCIPAL FINDINGS: We
      conducted a retrospective cohort study of adult patients insured by Harvard
      Pilgrim Health Care who were newly-detected to harbor MRSA between January 1991
      and December 2003 at a tertiary care medical center. We evaluated all MRSA
      attributable infections associated with hospitalization in the year following new
      detection, regardless of hospital location. Data were collected on comorbidities,
      healthcare utilization, mortality and MRSA outcomes. Of 591 newly-detected MRSA
      carriers, 23% were colonized and 77% were infected upon detection. In the year
      following detection, 196 (33%) patients developed 317 discrete and unrelated MRSA
      infections. The most common infections were pneumonia (34%), soft tissue (27%),
      and primary bloodstream (18%) infections. Infections occurred a median of 56 days
      post-detection. Of all infections, 26% involved bacteremia, and 17% caused MRSA
      attributable death. During the admission where MRSA was newly-detected, 14%
      (82/576) developed subsequent infection. Of those surviving to discharge, 24%
      (114/482) developed post-discharge infections in the year following detection.
      Half (99/185, 54%) of post-discharge infections caused readmission, and most
      (104/185, 55%) occurred over 90 days post-discharge. CONCLUSIONS/SIGNIFICANCE: In
      high-risk tertiary care patients, newly-detected MRSA carriage confers large
      risks of infection and substantial attributable mortality in the year following
      acquisition. Most infections occur post-discharge, and 18% of infections
      associated with readmission occurred in hospitals other than the one where MRSA
      was newly-detected. Despite gains in reducing MRSA infections during
      hospitalization, the risk of MRSA infection among critically and chronically ill
      carriers persists after discharge and warrants targeted prevention strategies.

PMID- 21949708
TI  - Pathogenic Neisseria hitchhike on the uropod of human neutrophils.
AB  - Polymorphonuclear neutrophils (PMNs) are important components of the human innate
      immune system and are rapidly recruited at the site of bacterial infection.
      Despite the effective phagocytic activity of PMNs, Neisseria gonorrhoeae
      infections are characterized by high survival within PMNs. We reveal a novel type
      IV pilus-mediated adherence of pathogenic Neisseria to the uropod (the rear) of
      polarized PMNs. The direct pilus-uropod interaction was visualized by scanning
      electron microscopy and total internal reflection fluorescence (TIRF) microscopy.
      We showed that N. meningitidis adhesion to the PMN uropod depended on both pilus
      associated proteins PilC1 and PilC2, while N. gonorrhoeae adhesion did not.
      Bacterial adhesion elicited accumulation of the complement regulator CD46, but
      not I-domain-containing integrins, beneath the adherent bacterial microcolony.
      Electrographs and live-cell imaging of PMNs suggested that bacterial adherence to
      the uropod is followed by internalization into PMNs via the uropod. We also
      present data showing that pathogenic Neisseria can hitchhike on PMNs to hide from
      their phagocytic activity as well as to facilitate the spread of the pathogen
      through the epithelial cell layer.

PMID- 21949709
TI  - The functioning of the Drosophila CPEB protein Orb is regulated by
      phosphorylation and requires casein kinase 2 activity.
AB  - The Orb CPEB protein regulates translation of localized mRNAs in Drosophila
      ovaries. While there are multiple hypo- and hyperphosphorylated Orb isoforms in
      wild type ovaries, most are missing in orb(F303), which has an amino acid
      substitution in a buried region of the second RRM domain. Using a proteomics
      approach we identified a candidate Orb kinase, Casein Kinase 2 (CK2). In addition
      to being associated with Orb in vivo, we show that ck2 is required for orb
      functioning in gurken signaling and in the autoregulation of orb mRNA
      localization and translation. Supporting a role for ck2 in Orb phosphorylation,
      we find that the phosphorylation pattern is altered when ck2 activity is
      partially compromised. Finally, we show that the Orb hypophosphorylated isoforms
      are in slowly sedimenting complexes that contain the translational repressor
      Bruno, while the hyperphosphorylated isoforms assemble into large complexes that
      co-sediment with polysomes and contain the Wisp poly(A) polymerase.

PMID- 21949710
TI  - Activation of JNK signaling mediates amyloid-beta-dependent cell death.
AB  - BACKGROUND: Alzheimer's disease (AD) is an age related progressive
      neurodegenerative disorder. One of the reasons for Alzheimer's neuropathology is
      the generation of large aggregates of Abeta42 that are toxic in nature and induce
      oxidative stress, aberrant signaling and many other cellular alterations that
      trigger neuronal cell death. However, the exact mechanisms leading to cell death
      are not clearly understood. METHODOLOGY/PRINCIPAL FINDINGS: We employed a
      Drosophila eye model of AD to study how Abeta42 causes cell death. Misexpression
      of higher levels of Abeta42 in the differentiating photoreceptors of fly retina
      rapidly induced aberrant cellular phenotypes and cell death. We found that
      blocking caspase-dependent cell death initially blocked cell death but did not
      lead to a significant rescue in the adult eye. However, blocking the levels of c
      Jun NH(2)-terminal kinase (JNK) signaling pathway significantly rescued the
      neurodegeneration phenotype of Abeta42 misexpression both in eye imaginal disc as
      well as the adult eye. Misexpression of Abeta42 induced transcriptional
      upregulation of puckered (puc), a downstream target and functional read out of
      JNK signaling. Moreover, a three-fold increase in phospho-Jun (activated Jun)
      protein levels was seen in Abeta42 retina as compared to the wild-type retina.
      When we blocked both caspases and JNK signaling simultaneously in the fly retina,
      the rescue of the neurodegenerative phenotype is comparable to that caused by
      blocking JNK signaling pathway alone. CONCLUSIONS/SIGNIFICANCE: Our data suggests
      that (i) accumulation of Abeta42 plaques induces JNK signaling in neurons and
      (ii) induction of JNK contributes to Abeta42 mediated cell death. Therefore,
      inappropriate JNK activation may indeed be relevant to the AD neuropathology,
      thus making JNK a key target for AD therapies.

PMID- 21949711
TI  - High prevalence of abdominal, intra-abdominal and subcutaneous adiposity and
      clustering of risk factors among urban Asian Indians in North India.
AB  - OBJECTIVE: To assess the prevalence of abdominal obesity including intra
      abdominal and subcutaneous adiposity along with other cardiometabolic risk
      factors in urban Asian Indians living in New Delhi. METHODS: We conducted a cross
      sectional epidemiological descriptive study with 459 subjects (217 males and 242
      females), representing all socio-economic strata in New Delhi. The anthropometric
      profile [body mass index (BMI), waist circumference (WC) and skinfold thickness],
      fasting blood glucose (FBG) and lipid profile were recorded. Percent body fat
      (%BF), total abdominal fat (TAF), intra-abdominal adipose tissue (IAAT) and
      subcutaneous abdominal adipose tissue (SCAT) were quantified using predictive
      equations for Asian Indians. RESULTS: The overall prevalence of obesity was high
      [by BMI (>25 kg/m(2)), 50.1%]. The prevalence of abdominal obesity (as assessed
      by WC) was 68.9%, while that assessed by TAF was 70.8%. Increased IAAT was
      significantly higher in females (80.6%) as compared to males (56.7%) (p = 0.00)
      with overall prevalence being 69.3%. The overall prevalence of high SCAT was
      67.8%, more in males (69.1%) vs. females (66.5%, p = 0.5). The prevalence of type
      2 diabetes, the metabolic syndrome and hypertension was 8.5%, 45.3% and 29.2%,
      respectively. Hypertriglyceridemia, hypercholesterolemia and low levels of HDL-c
      were prevalent in 42.7%, 26.6% and 37% of the subjects, respectively. The
      prevalence of hypertriglyceridemia was significantly higher in males (p = 0.007);
      however, low levels of HDL-c were more prevalent in females as compared to males
      (p = 0.00). CONCLUSION: High prevalence of generalized obesity, abdominal obesity
      (by measurement of WC, TAF, IAAT and SCAT) and dysmetabolic state in urban Asian
      Indians in north India need immediate public health intervention.

PMID- 21949712
TI  - Extending brain-training to the affective domain: increasing cognitive and
      affective executive control through emotional working memory training.
AB  - So-called 'brain-training' programs are a huge commercial success. However,
      empirical evidence regarding their effectiveness and generalizability remains
      equivocal. This study investigated whether brain-training (working memory [WM]
      training) improves cognitive functions beyond the training task (transfer
      effects), especially regarding the control of emotional material since it
      constitutes much of the information we process daily. Forty-five participants
      received WM training using either emotional or neutral material, or an
      undemanding control task. WM training, regardless of training material, led to
      transfer gains on another WM task and in fluid intelligence. However, only brain
      training with emotional material yielded transferable gains to improved control
      over affective information on an emotional Stroop task. The data support the
      reality of transferable benefits of demanding WM training and suggest that
      transferable gains across to affective contexts require training with material
      congruent to those contexts. These findings constitute preliminary evidence that
      intensive cognitively demanding brain-training can improve not only our abstract
      problem-solving capacity, but also ameliorate cognitive control processes (e.g.
      decision-making) in our daily emotive environments.

PMID- 21949714
TI  - The chitinase-like protein YKL-40 modulates cystic fibrosis lung disease.
AB  - The chitinase-like protein YKL-40 was found to be increased in patients with
      severe asthma and chronic obstructive pulmonary disease (COPD), two disease
      conditions featuring neutrophilic infiltrates. Based on these studies and a
      previous report indicating that neutrophils secrete YKL-40, we hypothesized that
      YKL-40 plays a key role in cystic fibrosis (CF) lung disease, a prototypic
      neutrophilic disease. The aim of this study was (i) to analyze YKL-40 levels in
      human and murine CF lung disease and (ii) to investigate whether YKL-40 single
      nucleotide polymorphisms (SNPs) modulate CF lung disease severity. YKL-40 protein
      levels were quantified in serum and sputum supernatants from CF patients and
      control individuals. Levels of the murine homologue BRP-39 were analyzed in
      airway fluids from CF-like betaENaC-Tg mice. YKL-40SNPs were analyzed in CF
      patients. YKL-40 levels were increased in sputum supernatants and in serum from
      CF patients compared to healthy control individuals. Within CF patients, YKL-40
      levels were higher in sputum than in serum. BRP-39 levels were increased in
      airways fluids from betaENaC-Tg mice compared to wild-type littermates. In both
      CF patients and betaENaC-Tg mice, YKL-40/BRP-39 airway levels correlated with the
      severity of pulmonary obstruction. Two YKL-40 SNPs (rs871799 and rs880633) were
      found to modulate age-adjusted lung function in CF patients. YKL-40/BRP-39
      levelsare increased in human and murine CF airway fluids, correlate with
      pulmonary function and modulate CF lung disease severity genetically. These
      findings suggest YKL-40 as a potential biomarker in CF lung disease.

PMID- 21949713
TI  - Genetics of sputum gene expression in chronic obstructive pulmonary disease.
AB  - Previous expression quantitative trait loci (eQTL) studies have performed genetic
      association studies for gene expression, but most of these studies examined
      lymphoblastoid cell lines from non-diseased individuals. We examined the genetics
      of gene expression in a relevant disease tissue from chronic obstructive
      pulmonary disease (COPD) patients to identify functional effects of known
      susceptibility genes and to find novel disease genes. By combining gene
      expression profiling on induced sputum samples from 131 COPD cases from the
      ECLIPSE Study with genomewide single nucleotide polymorphism (SNP) data, we found
      4315 significant cis-eQTL SNP-probe set associations (3309 unique SNPs). The 3309
      SNPs were tested for association with COPD in a genomewide association study
      (GWAS) dataset, which included 2940 COPD cases and 1380 controls. Adjusting for
      3309 tests (p<1.5e-5), the two SNPs which were significantly associated with COPD
      were located in two separate genes in a known COPD locus on chromosome 15: CHRNA5
      and IREB2. Detailed analysis of chromosome 15 demonstrated additional eQTLs for
      IREB2 mapping to that gene. eQTL SNPs for CHRNA5 mapped to multiple linkage
      disequilibrium (LD) bins. The eQTLs for IREB2 and CHRNA5 were not in LD. Seventy
      four additional eQTL SNPs were associated with COPD at p<0.01. These were
      genotyped in two COPD populations, finding replicated associations with a SNP in
      PSORS1C1, in the HLA-C region on chromosome 6. Integrative analysis of GWAS and
      gene expression data from relevant tissue from diseased subjects has located
      potential functional variants in two known COPD genes and has identified a novel
      COPD susceptibility locus.

PMID- 21949715
TI  - Universal behaviors as candidate traditions in wild spider monkeys.
AB  - Candidate traditions were documented across three communities of wild spider
      monkeys (Ateles geoffroyi) using an a priori approach to identify behavioral
      variants and a statistical approach to examine differences in their proportional
      use. This methodology differs from previous studies of animal traditions, which
      used retrospective data and relied on the 'exclusion method' to identify
      candidate traditions. Our a priori approach increased the likelihood that
      behavior variants with equivalent functions were considered and our statistical
      approach enabled the proportional use of 'universal' behaviors, i.e., used across
      all communities, to be examined for the first time in any animal species as
      candidate traditions. Among universal behaviors we found 14 'community preferred'
      variants. After considering the extent to which community preferred variants were
      due to ecological and, to a lesser degree, genetic differences, we concluded that
      at least six were likely maintained through social learning. Our findings have
      two main implications: (i) tradition repertoires could be larger than assumed
      from previous studies using the exclusion method; (ii) the relative use of
      universal behavior variants can reinforce community membership.

PMID- 21949716
TI  - A phase 1 trial of MSP2-C1, a blood-stage malaria vaccine containing 2 isoforms
      of MSP2 formulated with Montanide(r) ISA 720.
AB  - BACKGROUND: In a previous Phase 1/2b malaria vaccine trial testing the 3D7
      isoform of the malaria vaccine candidate Merozoite surface protein 2 (MSP2),
      parasite densities in children were reduced by 62%. However, breakthrough
      parasitemias were disproportionately of the alternate dimorphic form of MSP2, the
      FC27 genotype. We therefore undertook a dose-escalating, double-blinded, placebo
      controlled Phase 1 trial in healthy, malaria-naive adults of MSP2-C1, a vaccine
      containing recombinant forms of the two families of msp2 alleles, 3D7 and FC27
      (EcMSP2-3D7 and EcMSP2-FC27), formulated in equal amounts with Montanide(r) ISA
      720 as a water-in-oil emulsion. METHODOLOGY/PRINCIPAL FINDINGS: The trial was
      designed to include three dose cohorts (10, 40, and 80 ug), each with twelve
      subjects receiving the vaccine and three control subjects receiving Montanide(r)
      ISA 720 adjuvant emulsion alone, in a schedule of three doses at 12-week
      intervals. Due to unexpected local reactogenicity and concern regarding vaccine
      stability, the trial was terminated after the second immunisation of the cohort
      receiving the 40 ug dose; no subjects received the 80 ug dose. Immunization
      induced significant IgG responses to both isoforms of MSP2 in the 10 ug and 40 ug
      dose cohorts, with antibody levels by ELISA higher in the 40 ug cohort. Vaccine
      induced antibodies recognised native protein by Western blots of parasite protein
      extracts and by immunofluorescence microscopy. Although the induced anti-MSP2
      antibodies did not directly inhibit parasite growth in vitro, IgG from the
      majority of individuals tested caused significant antibody-dependent cellular
      inhibition (ADCI) of parasite growth. CONCLUSIONS/SIGNIFICANCE: As the majority
      of subjects vaccinated with MSP2-C1 developed an antibody responses to both forms
      of MSP2, and that these antibodies mediated ADCI provide further support for MSP2
      as a malaria vaccine candidate. However, in view of the reactogenicity of this
      formulation, further clinical development of MSP2-C1 will require formulation of
      MSP2 in an alternative adjuvant. TRIAL REGISTRATION: Australian New Zealand
      Clinical Trials Registry 12607000552482.

PMID- 21949717
TI  - Effects of transport inhibitors on the cellular uptake of carboxylated
      polystyrene nanoparticles in different cell lines.
AB  - Nanotechnology is expected to play a vital role in the rapidly developing field
      of nanomedicine, creating innovative solutions and therapies for currently
      untreatable diseases, and providing new tools for various biomedical
      applications, such as drug delivery and gene therapy. In order to optimize the
      efficacy of nanoparticle (NP) delivery to cells, it is necessary to understand
      the mechanisms by which NPs are internalized by cells, as this will likely
      determine their ultimate sub-cellular fate and localisation. Here we have used
      pharmacological inhibitors of some of the major endocytic pathways to investigate
      nanoparticle uptake mechanisms in a range of representative human cell lines,
      including HeLa (cervical cancer), A549 (lung carcinoma) and 1321N1 (brain
      astrocytoma). Chlorpromazine and genistein were used to inhibit clathrin and
      caveolin mediated endocytosis, respectively. Cytochalasin A and nocodazole were
      used to inhibit, respectively, the polymerisation of actin and microtubule
      cytoskeleton. Uptake experiments were performed systematically across the
      different cell lines, using carboxylated polystyrene NPs of 40 nm and 200 nm
      diameters, as model NPs of sizes comparable to typical endocytic cargoes. The
      results clearly indicated that, in all cases and cell types, NPs entered cells
      via active energy dependent processes. NP uptake in HeLa and 1321N1 cells was
      strongly affected by actin depolymerisation, while A549 cells showed a stronger
      inhibition of NP uptake (in comparison to the other cell types) after microtubule
      disruption and treatment with genistein. A strong reduction of NP uptake was
      observed after chlorpromazine treatment only in the case of 1321N1 cells. These
      outcomes suggested that the same NP might exploit different uptake mechanisms to
      enter different cell types.

PMID- 21949718
TI  - Transmission of aerosolized seasonal H1N1 influenza A to ferrets.
AB  - Influenza virus is a major cause of morbidity and mortality worldwide, yet little
      quantitative understanding of transmission is available to guide evidence-based
      public health practice. Recent studies of influenza non-contact transmission
      between ferrets and guinea pigs have provided insights into the relative
      transmission efficiencies of pandemic and seasonal strains, but the infecting
      dose and subsequent contagion has not been quantified for most strains. In order
      to measure the aerosol infectious dose for 50% (aID(50)) of seronegative ferrets,
      seasonal influenza virus was nebulized into an exposure chamber with controlled
      airflow limiting inhalation to airborne particles less than 5 um diameter.
      Airborne virus was collected by liquid impinger and Teflon filters during
      nebulization of varying doses of aerosolized virus. Since culturable virus was
      accurately captured on filters only up to 20 minutes, airborne viral RNA
      collected during 1-hour exposures was quantified by two assays, a high-throughput
      RT-PCR/mass spectrometry assay detecting 6 genome segments (Ibis T5000TM
      Biosensor system) and a standard real time RT-qPCR assay. Using the more
      sensitive T5000 assay, the aID(50) for A/New Caledonia/20/99 (H1N1) was
      approximately 4 infectious virus particles under the exposure conditions used.
      Although seroconversion and sustained levels of viral RNA in upper airway
      secretions suggested established mucosal infection, viral cultures were almost
      always negative. Thus after inhalation, this seasonal H1N1 virus may replicate
      less efficiently than H3N2 virus after mucosal deposition and exhibit less
      contagion after aerosol exposure.

PMID- 21949719
TI  - ST2 and IL-33 in pregnancy and pre-eclampsia.
AB  - Normal pregnancy is associated with a mild systemic inflammatory response and an
      immune bias towards type 2 cytokine production, whereas pre-eclampsia is
      characterized by a more intense inflammatory response, associated with
      endothelial dysfunction and a type 1 cytokine dominance. Interleukin (IL)-33 is a
      newly described member of the IL-1 family, which binds its receptor ST2L to
      induce type 2 cytokines. A soluble variant of ST2 (sST2) acts as a decoy receptor
      to regulate the activity of IL-33. In this study circulating IL-33 and sST2 were
      measured in each trimester of normal pregnancy and in women with pre-eclampsia.
      While IL-33 did not change throughout normal pregnancy, or between non-pregnant,
      normal pregnant or pre-eclamptic women, sST2 was significantly altered. sST2 was
      increased in the third trimester of normal pregnancy (p<0.001) and was further
      increased in pre-eclampsia (p<0.001). This increase was seen prior to the onset
      of disease (p<0.01). Pre-eclampsia is a disease caused by placental derived
      factors, and we show that IL-33 and ST2 can be detected in lysates from both
      normal and pre-eclampsia placentas. ST2, but not IL-33, was identified on the
      syncytiotrophoblast layer, whereas IL-33 was expressed on perivascular tissue. In
      an in vitro placental perfusion model, sST2 was secreted by the placenta into the
      'maternal' eluate, and placental explants treated with pro-inflammatory cytokines
      or subjected to hypoxia/reperfusion injury release more sST2, suggesting the
      origin of at least some of the increased amounts of circulating sST2 in pre
      eclamptic women is the placenta. These results suggest that sST2 may play a
      significant role in pregnancies complicated by pre-eclampsia and increased sST2
      could contribute to the type 1 bias seen in this disorder.

PMID- 21949720
TI  - Late replicating domains are highly recombining in females but have low male
      recombination rates: implications for isochore evolution.
AB  - In mammals sequences that are either late replicating or highly recombining have
      high rates of evolution at putatively neutral sites. As early replicating domains
      and highly recombining domains both tend to be GC rich we a priori expect these
      two variables to covary. If so, the relative contribution of either of these
      variables to the local neutral substitution rate might have been wrongly
      estimated owing to covariance with the other. Against our expectations, we find
      that sex-averaged recombination rates show little or no correlation with
      replication timing, suggesting that they are independent determinants of
      substitution rates. However, this result masks significant sex-specific
      complexity: late replicating domains tend to have high recombination rates in
      females but low recombination rates in males. That these trends are antagonistic
      explains why sex-averaged recombination is not correlated with replication
      timing. This unexpected result has several important implications. First,
      although both male and female recombination rates covary significantly with
      intronic substitution rates, the magnitude of this correlation is moderately
      underestimated for male recombination and slightly overestimated for female
      recombination, owing to covariance with replicating timing. Second, the result
      could explain why male recombination is strongly correlated with GC content but
      female recombination is not. If to explain the correlation between GC content and
      replication timing we suppose that late replication forces reduced GC content,
      then GC promotion by biased gene conversion during female recombination is partly
      countered by the antagonistic effect of later replicating sequence tending
      increase AT content. Indeed, the strength of the correlation between female
      recombination rate and local GC content is more than doubled by control for
      replication timing. Our results underpin the need to consider sex-specific
      recombination rates and potential covariates in analysis of GC content and rates
      of evolution.

PMID- 21949721
TI  - A new troodontid theropod, Talos sampsoni gen. et sp. nov., from the Upper
      Cretaceous Western Interior Basin of North America.
AB  - BACKGROUND: Troodontids are a predominantly small-bodied group of feathered
      theropod dinosaurs notable for their close evolutionary relationship with
      Avialae. Despite a diverse Asian representation with remarkable growth in recent
      years, the North American record of the clade remains poor, with only one
      controversial species--Troodon formosus--presently known from substantial
      skeletal remains. METHODOLOGY/PRINCIPAL FINDINGS: Here we report a gracile new
      troodontid theropod--Talos sampsoni gen. et sp. nov.--from the Upper Cretaceous
      Kaiparowits Formation, Utah, USA, representing one of the most complete
      troodontid skeletons described from North America to date. Histological
      assessment of the holotype specimen indicates that the adult body size of Talos
      was notably smaller than that of the contemporary genus Troodon. Phylogenetic
      analysis recovers Talos as a member of a derived, latest Cretaceous subclade,
      minimally containing Troodon, Saurornithoides, and Zanabazar. MicroCT scans
      reveal extreme pathological remodeling on pedal phalanx II-1 of the holotype
      specimen likely resulting from physical trauma and subsequent infectious
      processes. CONCLUSION/SIGNIFICANCE: Talos sampsoni adds to the singularity of the
      Kaiparowits Formation dinosaur fauna, which is represented by at least 10
      previously unrecognized species including the recently named ceratopsids
      Utahceratops and Kosmoceratops, the hadrosaurine Gryposaurus monumentensis, the
      tyrannosaurid Teratophoneus, and the oviraptorosaurian Hagryphus. The presence of
      a distinct troodontid taxon in the Kaiparowits Formation supports the hypothesis
      that late Campanian dinosaurs of the Western Interior Basin exhibited restricted
      geographic ranges and suggests that the taxonomic diversity of Late Cretaceous
      troodontids from North America is currently underestimated. An apparent traumatic
      injury to the foot of Talos with evidence of subsequent healing sheds new light
      on the paleobiology of deinonychosaurians by bolstering functional
      interpretations of prey grappling and/or intraspecific combat for the second
      pedal digit, and supporting trackway evidence indicating a minimal role in weight
      bearing.

PMID- 21949722
TI  - Human metapneumovirus inhibits IFN-beta signaling by downregulating Jak1 and Tyk2
      cellular levels.
AB  - Human metapneumovirus (hMPV), a leading cause of respiratory tract infections in
      infants, inhibits type I interferon (IFN) signaling by an unidentified mechanism.
      In this study, we showed that infection of airway epithelial cells with hMPV
      decreased cellular level of Janus tyrosine kinase (Jak1) and tyrosine kinase 2
      (Tyk2), due to enhanced proteosomal degradation and reduced gene transcription.
      In addition, hMPV infection also reduced the surface expression of type I IFN
      receptor (IFNAR). These inhibitory mechanisms are different from the ones
      employed by respiratory syncytial virus (RSV), which does not affect Jak1, Tyk2
      or IFNAR expression, but degrades downstream signal transducer and activator of
      transcription proteins 2 (STAT2), although both viruses are pneumoviruses
      belonging to the Paramyxoviridae family. Our study identifies a novel mechanism
      by which hMPV inhibits STAT1 and 2 activation, ultimately leading to viral
      evasion of host IFN responses.

PMID- 21949723
TI  - The roots of diversity: below ground species richness and rooting distributions
      in a tropical forest revealed by DNA barcodes and inverse modeling.
AB  - BACKGROUND: Plants interact with each other, nutrients, and microbial communities
      in soils through extensive root networks. Understanding these below ground
      interactions has been difficult in natural systems, particularly those with high
      plant species diversity where morphological identification of fine roots is
      difficult. We combine DNA-based root identification with a DNA barcode database
      and above ground stem locations in a floristically diverse lowland tropical wet
      forest on Barro Colorado Island, Panama, where all trees and lianas >1 cm
      diameter have been mapped to investigate richness patterns below ground and model
      rooting distributions. METHODOLOGY/PRINCIPAL FINDINGS: DNA barcode loci,
      particularly the cpDNA locus trnH-psba, can be used to identify fine and small
      coarse roots to species. We recovered 33 species of roots from 117 fragments
      sequenced from 12 soil cores. Despite limited sampling, we recovered a high
      proportion of the known species in the focal hectare, representing approximately
      14% of the measured woody plant richness. This high value is emphasized by the
      fact that we would need to sample on average 13 m(2) at the seedling layer and 45
      m(2) for woody plants >1 cm diameter to obtain the same number of species above
      ground. Results from inverse models parameterized with the locations and sizes of
      adults and the species identifications of roots and sampling locations indicates
      a high potential for distal underground interactions among plants. CONCLUSIONS:
      DNA barcoding techniques coupled with modeling approaches should be broadly
      applicable to studying root distributions in any mapped vegetation plot. We
      discuss the implications of our results and outline how second-generation
      sequencing technology and environmental sampling can be combined to increase our
      understanding of how root distributions influence the potential for plant
      interactions in natural ecosystems.

PMID- 21949724
TI  - Spontaneous abortion and preterm labor and delivery in nonhuman primates:
      evidence from a captive colony of chimpanzees (Pan troglodytes).
AB  - BACKGROUND: Preterm birth is a leading cause of perinatal mortality, yet the
      evolutionary history of this obstetrical syndrome is largely unknown in nonhuman
      primate species. METHODOLOGY/PRINCIPAL FINDINGS: We examined the length of
      gestation during pregnancies that occurred in a captive chimpanzee colony by
      inspecting veterinary and behavioral records spanning a total of thirty years.
      Upon examination of these records we were able to confidently estimate gestation
      length for 93 of the 97 (96%) pregnancies recorded at the colony. In total, 78
      singleton gestations resulted in live birth, and from these pregnancies we
      estimated the mean gestation length of normal chimpanzee pregnancies to be 228
      days, a finding consistent with other published reports. We also calculated that
      the range of gestation in normal chimpanzee pregnancies is approximately forty
      days. Of the remaining fifteen pregnancies, only one of the offspring survived,
      suggesting viability for chimpanzees requires a gestation of approximately 200
      days. These fifteen pregnancies constitute spontaneous abortions and preterm
      deliveries, for which the upper gestational age limit was defined as 2 SD from
      the mean length of gestation (208 days). CONCLUSIONS/SIGNIFICANCE: The present
      study documents that preterm birth occurred within our study population of
      captive chimpanzees. As in humans, pregnancy loss is not uncommon in chimpanzees,
      In addition, our findings indicate that both humans and chimpanzees show a
      similar range of normal variation in gestation length, suggesting this was the
      case at the time of their last common ancestor (LCA). Nevertheless, our data
      suggest that whereas chimpanzees' normal gestation length is ~20-30 days after
      reaching viability, humans' normal gestation length is approximately 50 days
      beyond the estimated date of viability without medical intervention. Future
      research using a comparative evolutionary framework should help to clarify the
      extent to which mechanisms at work in normal and preterm parturition are shared
      in these species.

PMID- 21949725
TI  - Composition and acidification of the culture medium influences chronological
      aging similarly in vineyard and laboratory yeast.
AB  - Chronological aging has been studied extensively in laboratory yeast by culturing
      cells into stationary phase in synthetic complete medium with 2% glucose as the
      carbon source. During this process, acidification of the culture medium occurs
      due to secretion of organic acids, including acetic acid, which limits survival
      of yeast cells. Dietary restriction or buffering the medium to pH 6 prevents
      acidification and increases chronological life span. Here we set out to determine
      whether these effects are specific to laboratory-derived yeast by testing the
      chronological aging properties of the vineyard yeast strain RM11. Similar to the
      laboratory strain BY4743 and its haploid derivatives, RM11 and its haploid
      derivatives displayed increased chronological life span from dietary restriction,
      buffering the pH of the culture medium, or aging in rich medium. RM11 and BY4743
      also displayed generally similar aging and growth characteristics when cultured
      in a variety of different carbon sources. These data support the idea that
      mechanisms of chronological aging are similar in both the laboratory and vineyard
      strains.

PMID- 21949726
TI  - Peptide bond distortions from planarity: new insights from quantum mechanical
      calculations and peptide/protein crystal structures.
AB  - By combining quantum-mechanical analysis and statistical survey of
      peptide/protein structure databases we here report a thorough investigation of
      the conformational dependence of the geometry of peptide bond, the basic element
      of protein structures. Different peptide model systems have been studied by an
      integrated quantum mechanical approach, employing DFT, MP2 and CCSD(T)
      calculations, both in aqueous solution and in the gas phase. Also in absence of
      inter-residue interactions, small distortions from the planarity are more a rule
      than an exception, and they are mainly determined by the backbone psi dihedral
      angle. These indications are fully corroborated by a statistical survey of
      accurate protein/peptide structures. Orbital analysis shows that orbital
      interactions between the sigma system of C(alpha) substituents and the pi system
      of the amide bond are crucial for the modulation of peptide bond distortions. Our
      study thus indicates that, although long-range inter-molecular interactions can
      obviously affect the peptide planarity, their influence is statistically
      averaged. Therefore, the variability of peptide bond geometry in proteins is
      remarkably reproduced by extremely simplified systems since local factors are the
      main driving force of these observed trends. The implications of the present
      findings for protein structure determination, validation and prediction are also
      discussed.

PMID- 21949728
TI  - High resolution analysis of the chromatin landscape of the IgE switch region in
      human B cells.
AB  - Antibodies are assembled by a highly orchestrated series of recombination events
      during B cell development. One of these events, class switch recombination, is
      required to produce the IgG, IgE and IgA antibody isotypes characteristic of a
      secondary immune response. The action of the enzyme activation induced cytidine
      deaminase is now known to be essential for the initiation of this recombination
      event. Previous studies have demonstrated that the immunoglobulin switch regions
      acquire distinct histone modifications prior to recombination. We now present a
      high resolution analysis of these histone modifications across the IgE switch
      region prior to the initiation of class switch recombination in primary human B
      cells and the human CL-01 B cell line. These data show that upon stimulation with
      IL-4 and an anti-CD40 antibody that mimics T cell help, the nucleosomes of the
      switch regions are highly modified on histone H3, accumulating acetylation marks
      and tri-methylation of lysine 4. Distinct peaks of modified histones are found
      across the switch region, most notably at the 5' splice donor site of the
      germline (I) exon, which also accumulates AID. These data suggest that
      acetylation and K4 tri-methylation of histone H3 may represent marks of
      recombinationally active chromatin and further implicates splicing in the
      regulation of AID action.

PMID- 21949727
TI  - The plant pathogen Phytophthora andina emerged via hybridization of an unknown
      Phytophthora species and the Irish potato famine pathogen, P. infestans.
AB  - Emerging plant pathogens have largely been a consequence of the movement of
      pathogens to new geographic regions. Another documented mechanism for the
      emergence of plant pathogens is hybridization between individuals of different
      species or subspecies, which may allow rapid evolution and adaptation to new
      hosts or environments. Hybrid plant pathogens have traditionally been difficult
      to detect or confirm, but the increasing ease of cloning and sequencing PCR
      products now makes the identification of species that consistently have genes or
      alleles with phylogenetically divergent origins relatively straightforward. We
      investigated the genetic origin of Phytophthora andina, an increasingly common
      pathogen of Andean crops Solanum betaceum, S. muricatum, S. quitoense, and
      several wild Solanum spp. It has been hypothesized that P. andina is a hybrid
      between the potato late blight pathogen P. infestans and another Phytophthora
      species. We tested this hypothesis by cloning four nuclear loci to obtain
      haplotypes and using these loci to infer the phylogenetic relationships of P.
      andina to P. infestans and other related species. Sequencing of cloned PCR
      products in every case revealed two distinct haplotypes for each locus in P.
      andina, such that each isolate had one allele derived from a P. infestans parent
      and a second divergent allele derived from an unknown species that is closely
      related but distinct from P. infestans, P. mirabilis, and P. ipomoeae. To the
      best of our knowledge, the unknown parent has not yet been collected. We also
      observed sequence polymorphism among P. andina isolates at three of the four
      loci, many of which segregate between previously described P. andina clonal
      lineages. These results provide strong support that P. andina emerged via
      hybridization between P. infestans and another unknown Phytophthora species also
      belonging to Phytophthora clade 1c.

PMID- 21949729
TI  - A complete solution for dissecting pure main and epistatic effects of QTL in
      triple testcross design.
AB  - Epistasis plays an important role in genetics, evolution and crop breeding. To
      detect the epistasis, triple test cross (TTC) design had been developed several
      decades ago. Classical procedures for the TTC design use only linear
      transformations Z(1), Z(2) and Z(3), calculated from the TTC family means of
      quantitative trait, to infer the nature of the collective additive, dominance and
      epistatic effects of all the genes. Although several quantitative trait loci
      (QTL) mapping approaches in the TTC design have been developed, these approaches
      do not provide a complete solution for dissecting pure main and epistatic
      effects. In this study, therefore, we developed a two-step approach to estimate
      all pure main and epistatic effects in the F(2)-based TTC design under the F(2)
      and F(infinity) metric models. In the first step, with Z(1) and Z(2) the
      augmented main and epistatic effects in the full genetic model that
      simultaneously considered all putative QTL on the whole genome were estimated
      using empirical Bayes approach, and with Z(3) three pure epistatic effects were
      obtained using two-dimensional genome scans. In the second step, the three pure
      epistatic effects obtained in the first step were integrated with the augmented
      epistatic and main effects for the further estimation of all other pure effects.
      A series of Monte Carlo simulation experiments has been carried out to confirm
      the proposed method. The results from simulation experiments show that: 1) the
      newly defined genetic parameters could be rightly identified with satisfactory
      statistical power and precision; 2) the F(2)-based TTC design was superior to the
      F(2) and F(2:3) designs; 3) with Z(1) and Z(2) the statistical powers for the
      detection of augmented epistatic effects were substantively affected by the signs
      of pure epistatic effects; and 4) with Z(3) the estimation of pure epistatic
      effects required large sample size and family replication number. The extension
      of the proposed method in this study to other base populations was further
      discussed.

PMID- 21949730
TI  - Gene signatures derived from a c-MET-driven liver cancer mouse model predict
      survival of patients with hepatocellular carcinoma.
AB  - Biomarkers derived from gene expression profiling data may have a high false
      positive rate and must be rigorously validated using independent clinical data
      sets, which are not always available. Although animal model systems could provide
      alternative data sets to formulate hypotheses and limit the number of signatures
      to be tested in clinical samples, the predictive power of such an approach is not
      yet proven. The present study aims to analyze the molecular signatures of liver
      cancer in a c-MET-transgenic mouse model and investigate its prognostic relevance
      to human hepatocellular carcinoma (HCC). Tissue samples were obtained from tumor
      (TU), adjacent non-tumor (AN) and distant normal (DN) liver in Tet-operator
      regulated (TRE) human c-MET transgenic mice (n = 21) as well as from a Chinese
      cohort of 272 HBV- and 9 HCV-associated HCC patients. Whole genome microarray
      expression profiling was conducted in Affymetrix gene expression chips, and
      prognostic significances of gene expression signatures were evaluated across the
      two species. Our data revealed parallels between mouse and human liver tumors,
      including down-regulation of metabolic pathways and up-regulation of cell cycle
      processes. The mouse tumors were most similar to a subset of patient samples
      characterized by activation of the Wnt pathway, but distinctive in the p53
      pathway signals. Of potential clinical utility, we identified a set of genes that
      were down regulated in both mouse tumors and human HCC having significant
      predictive power on overall and disease-free survival, which were highly enriched
      for metabolic functions. In conclusions, this study provides evidence that a
      disease model can serve as a possible platform for generating hypotheses to be
      tested in human tissues and highlights an efficient method for generating
      biomarker signatures before extensive clinical trials have been initiated.

PMID- 21949731
TI  - MultiMiTar: a novel multi objective optimization based miRNA-target prediction
      method.
AB  - BACKGROUND: Machine learning based miRNA-target prediction algorithms often fail
      to obtain a balanced prediction accuracy in terms of both sensitivity and
      specificity due to lack of the gold standard of negative examples, miRNA
      targeting site context specific relevant features and efficient feature selection
      process. Moreover, all the sequence, structure and machine learning based
      algorithms are unable to distribute the true positive predictions preferentially
      at the top of the ranked list; hence the algorithms become unreliable to the
      biologists. In addition, these algorithms fail to obtain considerable combination
      of precision and recall for the target transcripts that are translationally
      repressed at protein level. METHODOLOGY/PRINCIPAL FINDING: In the proposed
      article, we introduce an efficient miRNA-target prediction system MultiMiTar, a
      Support Vector Machine (SVM) based classifier integrated with a multiobjective
      metaheuristic based feature selection technique. The robust performance of the
      proposed method is mainly the result of using high quality negative examples and
      selection of biologically relevant miRNA-targeting site context specific
      features. The features are selected by using a novel feature selection technique
      AMOSA-SVM, that integrates the multi objective optimization technique Archived
      Multi-Objective Simulated Annealing (AMOSA) and SVM. CONCLUSIONS/SIGNIFICANCE:
      MultiMiTar is found to achieve much higher Matthew's correlation coefficient
      (MCC) of 0.583 and average class-wise accuracy (ACA) of 0.8 compared to the
      others target prediction methods for a completely independent test data set. The
      obtained MCC and ACA values of these algorithms range from -0.269 to 0.155 and
      0.321 to 0.582, respectively. Moreover, it shows a more balanced result in terms
      of precision and sensitivity (recall) for the translationally repressed data set
      as compared to all the other existing methods. An important aspect is that the
      true positive predictions are distributed preferentially at the top of the ranked
      list that makes MultiMiTar reliable for the biologists. MultiMiTar is now
      available as an online tool at www.isical.ac.in/~bioinfo_miu/multimitar.htm.
      MultiMiTar software can be downloaded from
      www.isical.ac.in/~bioinfo_miu/multimitar-download.htm.

PMID- 21949733
TI  - Glatiramer acetate treatment normalizes deregulated microRNA expression in
      relapsing remitting multiple sclerosis.
AB  - The expression of selected microRNAs (miRNAs) known to be involved in the
      regulation of immune responses was analyzed in 74 patients with relapsing
      remitting multiple sclerosis (RRMS) and 32 healthy controls. Four miRNAs (miR
      326, miR-155, miR-146a, miR-142-3p) were aberrantly expressed in peripheral blood
      mononuclear cells from RRMS patients compared to controls. Although expression of
      these selected miRNAs did not differ between treatment-naive (n = 36) and
      interferon-beta treated RRMS patients (n = 18), expression of miR-146a and miR
      142-3p was significantly lower in glatiramer acetate (GA) treated RRMS patients
      (n = 20) suggesting that GA, at least in part, restores the expression of
      deregulated miRNAs in MS.

PMID- 21949734
TI  - Th17 cells are involved in the local control of tumor progression in primary
      intraocular lymphoma.
AB  - BACKGROUND: Th17 cells play an important role in the pathogenesis of many
      autoimmune diseases, but despite some reports of their antitumor properties, too
      little is known about their presence and role in cancers. Specifically, knowledge
      is sparse about the relation of Th17 to lymphoma microenvironments and, more
      particularly, to the microenvironment of primary intraocular B-cell lymphoma
      (PIOL), an aggressive lymphoma with a poor prognosis. METHODS AND PRINCIPAL
      FINDINGS: In this work, we investigated the presence of Th17 cells and their
      related cytokines in a syngeneic model of PIOL, a subtype of non-Hodgkin
      lymphoma. The very small number of lymphocytes trafficking in normal eyes, which
      represent a low background as compared to tumor-bearing eyes, allows us to
      develop the present model to characterize the different lymphocyte subsets
      present when a tumor is developing. IL-21 mRNA was expressed concomitantly with
      IL-17 mRNA in tumor-bearing eyes and intracellular expression of IL-17A and IL-21
      in infiltrating CD4(+) T lymphocytes. Interestingly, IL-17A production by T cells
      was negatively correlated with tumor burden. We also showed that IL-21 but not IL
      17 inhibits tumor cell proliferation in vitro. CONCLUSIONS: These data
      demonstrate that IL-17A and IL-21-producing CD4(+) T cells, referred as Th17
      cells, infiltrate this tumor locally and suggest that Th17-related cytokines may
      counteract tumor progression via IL-21 production. Thus, Th17 cells or their
      related cytokines could be considered to be a new therapeutic approach for non
      Hodgkin B-cell lymphomas, particularly those with an ocular localization.

PMID- 21949732
TI  - Impaired carbohydrate digestion and transport and mucosal dysbiosis in the
      intestines of children with autism and gastrointestinal disturbances.
AB  - Gastrointestinal disturbances are commonly reported in children with autism,
      complicate clinical management, and may contribute to behavioral impairment.
      Reports of deficiencies in disaccharidase enzymatic activity and of beneficial
      responses to probiotic and dietary therapies led us to survey gene expression and
      the mucoepithelial microbiota in intestinal biopsies from children with autism
      and gastrointestinal disease and children with gastrointestinal disease alone.
      Ileal transcripts encoding disaccharidases and hexose transporters were deficient
      in children with autism, indicating impairment of the primary pathway for
      carbohydrate digestion and transport in enterocytes. Deficient expression of
      these enzymes and transporters was associated with expression of the intestinal
      transcription factor, CDX2. Metagenomic analysis of intestinal bacteria revealed
      compositional dysbiosis manifest as decreases in Bacteroidetes, increases in the
      ratio of Firmicutes to Bacteroidetes, and increases in Betaproteobacteria.
      Expression levels of disaccharidases and transporters were associated with the
      abundance of affected bacterial phylotypes. These results indicate a relationship
      between human intestinal gene expression and bacterial community structure and
      may provide insights into the pathophysiology of gastrointestinal disturbances in
      children with autism.

PMID- 21949735
TI  - Cross-protective peptide vaccine against influenza A viruses developed in HLA
      A*2402 human immunity model.
AB  - BACKGROUND: The virus-specific cytotoxic T lymphocyte (CTL) induction is an
      important target for the development of a broadly protective human influenza
      vaccine, since most CTL epitopes are found on internal viral proteins and
      relatively conserved. In this study, the possibility of developing a
      strain/subtype-independent human influenza vaccine was explored by taking a
      bioinformatics approach to establish an immunogenic HLA-A24 restricted CTL
      epitope screening system in HLA-transgenic mice. METHODOLOGY/PRINCIPAL FINDINGS:
      HLA-A24 restricted CTL epitope peptides derived from internal proteins of the
      H5N1 highly pathogenic avian influenza A virus were predicted by CTL epitope
      peptide prediction programs. Of 35 predicted peptides, six peptides exhibited
      remarkable cytotoxic activity in vivo. More than half of the mice which were
      subcutaneously vaccinated with the three most immunogenic and highly conserved
      epitopes among three different influenza A virus subtypes (H1N1, H3N2 and H5N1)
      survived lethal influenza virus challenge during both effector and memory CTL
      phases. Furthermore, mice that were intranasally vaccinated with these peptides
      remained free of clinical signs after lethal virus challenge during the effector
      phase. CONCLUSIONS/SIGNIFICANCE: This CTL epitope peptide selection system can be
      used as an effective tool for the development of a cross-protective human
      influenza vaccine. Furthermore this vaccine strategy can be applicable to the
      development of all intracellular pathogens vaccines to induce epitope-specific
      CTL that effectively eliminate infected cells.

PMID- 21949736
TI  - Real-time contrast enhancement to improve speech recognition.
AB  - An algorithm that operates in real-time to enhance the salient features of speech
      is described and its efficacy is evaluated. The Contrast Enhancement (CE)
      algorithm implements dynamic compressive gain and lateral inhibitory sidebands
      across channels in a modified winner-take-all circuit, which together produce a
      form of suppression that sharpens the dynamic spectrum. Normal-hearing listeners
      identified spectrally smeared consonants (VCVs) and vowels (hVds) in quiet and in
      noise. Consonant and vowel identification, especially in noise, were improved by
      the processing. The amount of improvement did not depend on the degree of
      spectral smearing or talker characteristics. For consonants, when results were
      analyzed according to phonetic feature, the most consistent improvement was for
      place of articulation. This is encouraging for hearing aid applications because
      confusions between consonants differing in place are a persistent problem for
      listeners with sensorineural hearing loss.

PMID- 21949738
TI  - Manipulable objects facilitate cross-modal integration in peripersonal space.
AB  - Previous studies have shown that tool use often modifies one's peripersonal space
      -i.e. the space directly surrounding our body. Given our profound experience with
      manipulable objects (e.g. a toothbrush, a comb or a teapot) in the present study
      we hypothesized that the observation of pictures representing manipulable objects
      would result in a remapping of peripersonal space as well. Subjects were required
      to report the location of vibrotactile stimuli delivered to the right hand, while
      ignoring visual distractors superimposed on pictures representing everyday
      objects. Pictures could represent objects that were of high manipulability (e.g.
      a cell phone), medium manipulability (e.g. a soap dispenser) and low
      manipulability (e.g. a computer screen). In the first experiment, when subjects
      attended to the action associated with the objects, a strong cross-modal
      congruency effect (CCE) was observed for pictures representing medium and high
      manipulability objects, reflected in faster reaction times if the vibrotactile
      stimulus and the visual distractor were in the same location, whereas no CCE was
      observed for low manipulability objects. This finding was replicated in a second
      experiment in which subjects attended to the visual properties of the objects.
      These findings suggest that the observation of manipulable objects facilitates
      cross-modal integration in peripersonal space.

PMID- 21949737
TI  - Mycobacterial PIMs inhibit host inflammatory responses through CD14-dependent and
      CD14-independent mechanisms.
AB  - Mycobacteria develop strategies to evade the host immune system. Among them,
      mycobacterial LAM or PIMs inhibit the expression of pro-inflammatory cytokines by
      activated macrophages. Here, using synthetic PIM analogues, we analyzed the mode
      of action of PIM anti-inflammatory effects. Synthetic PIM(1) isomer and PIM(2)
      mimetic potently inhibit TNF and IL-12 p40 expression induced by TLR2 or TLR4
      pathways, but not by TLR9, in murine macrophages. We show inhibition of LPS
      binding to TLR4/MD2/CD14 expressing HEK cells by PIM(1) and PIM(2) analogues.
      More specifically, the binding of LPS to CD14 was inhibited by PIM(1) and PIM(2)
      analogues. CD14 was dispensable for PIM(1) and PIM(2) analogues functional
      inhibition of TLR2 agonists induced TNF, as shown in CD14-deficient macrophages.
      The use of rough-LPS, that stimulates TLR4 pathway independently of CD14, allowed
      to discriminate between CD14-dependent and CD14-independent anti-inflammatory
      effects of PIMs on LPS-induced macrophage responses. PIM(1) and PIM(2) analogues
      inhibited LPS-induced TNF release by a CD14-dependent pathway, while IL-12 p40
      inhibition was CD14-independent, suggesting that PIMs have multifold inhibitory
      effects on the TLR4 signalling pathway.

PMID- 21949740
TI  - Mechanism of the interaction between the intrinsically disordered C-terminus of
      the pro-apoptotic ARTS protein and the Bir3 domain of XIAP.
AB  - ARTS (Sept4_i2) is a mitochondrial pro-apoptotic protein that functions as a
      tumor suppressor. Its expression is significantly reduced in leukemia and
      lymphoma patients. ARTS binds and inhibits XIAP (X-linked Inhibitor of Apoptosis
      protein) by interacting with its Bir3 domain. ARTS promotes degradation of XIAP
      through the proteasome pathway. By doing so, ARTS removes XIAP inhibition of
      caspases and enables apoptosis to proceed. ARTS contains 27 unique residues in
      its C-terminal domain (CTD, residues 248-274) which are important for XIAP
      binding. Here we characterized the molecular details of this interaction.
      Biophysical and computational methods were used to show that the ARTS CTD is
      intrinsically disordered under physiological conditions. Direct binding of ARTS
      CTD to Bir3 was demonstrated using NMR and fluorescence spectroscopy. The Bir3
      interacting region in ARTS CTD was mapped to ARTS residues 266-274, which are the
      nine C-terminal residues in the protein. Alanine scan of ARTS 266-274 showed the
      importance of several residues for Bir3 binding, with His268 and Cys273
      contributing the most. Adding a reducing agent prevented binding to Bir3. A dimer
      of ARTS 266-274 formed by oxidation of the Cys residues into a disulfide bond
      bound with similar affinity and was probably required for the interaction with
      Bir3. The detailed analysis of the ARTS - Bir3 interaction provides the basis for
      setting it as a target for anti cancer drug design: It will enable the
      development of compounds that mimic ARTS CTD, remove IAPs inhibition of caspases,
      and thereby induce apoptosis.

PMID- 21949741
TI  - Accelerating protein docking in ZDOCK using an advanced 3D convolution library.
AB  - Computational prediction of the 3D structures of molecular interactions is a
      challenging area, often requiring significant computational resources to produce
      structural predictions with atomic-level accuracy. This can be particularly
      burdensome when modeling large sets of interactions, macromolecular assemblies,
      or interactions between flexible proteins. We previously developed a protein
      docking program, ZDOCK, which uses a fast Fourier transform to perform a 3D
      search of the spatial degrees of freedom between two molecules. By utilizing a
      pairwise statistical potential in the ZDOCK scoring function, there were notable
      gains in docking accuracy over previous versions, but this improvement in
      accuracy came at a substantial computational cost. In this study, we incorporated
      a recently developed 3D convolution library into ZDOCK, and additionally modified
      ZDOCK to dynamically orient the input proteins for more efficient convolution.
      These modifications resulted in an average of over 8.5-fold improvement in
      running time when tested on 176 cases in a newly released protein docking
      benchmark, as well as substantially less memory usage, with no loss in docking
      accuracy. We also applied these improvements to a previous version of ZDOCK that
      uses a simpler non-pairwise atomic potential, yielding an average speed
      improvement of over 5-fold on the docking benchmark, while maintaining predictive
      success. This permits the utilization of ZDOCK for more intensive tasks such as
      docking flexible molecules and modeling of interactomes, and can be run more
      readily by those with limited computational resources.

PMID- 21949739
TI  - The regulation of skeletal muscle protein turnover during the progression of
      cancer cachexia in the Apc(Min/+) mouse.
AB  - Muscle wasting that occurs with cancer cachexia is caused by an imbalance in the
      rates of muscle protein synthesis and degradation. The Apc(Min/+) mouse is a
      model of colorectal cancer that develops cachexia that is dependent on
      circulating IL-6. However, the IL-6 regulation of muscle protein turnover during
      the initiation and progression of cachexia in the Apc(Min/+) mouse is not known.
      Cachexia progression was studied in Apc(Min/+) mice that were either weight
      stable (WS) or had initial (<=5%), intermediate (6-19%), or extreme (>=20%) body
      weight loss. The initiation of cachexia reduced %MPS 19% and a further ~50% with
      additional weight loss. Muscle IGF-1 mRNA expression and mTOR targets were
      suppressed with the progression of body weight loss, while muscle AMPK
      phosphorylation (Thr 172), AMPK activity, and raptor phosphorylation (Ser 792)
      were not increased with the initiation of weight loss, but were induced as
      cachexia progressed. ATP dependent protein degradation increased during the
      initiation and progression of cachexia. However, ATP independent protein
      degradation was not increased until cachexia had progressed beyond the initial
      phase. IL-6 receptor antibody administration prevented body weight loss and
      suppressed muscle protein degradation, without any effect on muscle %MPS or IGF-1
      associated signaling. In summary, the %MPS reduction during the initiation of
      cachexia is associated with IGF-1/mTOR signaling repression, while muscle AMPK
      activation and activation of ATP independent protein degradation occur later in
      the progression of cachexia. IL-6 receptor antibody treatment blocked cachexia
      progression through the suppression of muscle protein degradation, while not
      rescuing the suppression of muscle protein synthesis. Attenuation of IL-6
      signaling was effective in blocking the progression of cachexia, but not
      sufficient to reverse the process.

PMID- 21949742
TI  - HCV causes chronic endoplasmic reticulum stress leading to adaptation and
      interference with the unfolded protein response.
AB  - BACKGROUND: The endoplasmic reticulum (ER) is the cellular site for protein
      folding. ER stress occurs when protein folding capacity is exceeded. This stress
      induces a cyto-protective signaling cascades termed the unfolded protein response
      (UPR) aimed at restoring homeostasis. While acute ER stress is lethal, chronic
      sub-lethal ER stress causes cells to adapt by attenuation of UPR activation.
      Hepatitis C virus (HCV), a major human pathogen, was shown to cause ER stress,
      however it is unclear whether HCV induces chronic ER stress, and if so whether
      adaptation mechanisms are initiated. We wanted to characterize the kinetics of
      HCV-induced ER stress during infection and assess adaptation mechanisms and their
      significance. METHODS AND FINDINGS: The HuH7.5.1 cellular system and HCV
      transgenic (HCV-Tg) mice were used to characterize HCV-induced ER stress/UPR
      pathway activation and adaptation. HCV induced a wave of acute ER stress peaking
      2-5 days post-infection, which rapidly subsided thereafter. UPR pathways were
      activated including IRE1 and EIF2alpha phosphorylation, ATF6 cleavage and XBP-1
      splicing. Downstream target genes including GADD34, ERdj4, p58ipk, ATF3 and ATF4
      were upregulated. CHOP, a UPR regulated protein was activated and translocated to
      the nucleus. Remarkably, UPR activity did not return to baseline but remained
      elevated for up to 14 days post infection suggesting that chronic ER stress is
      induced. At this time, cells adapted to ER stress and were less responsive to
      further drug-induced ER stress. Similar results were obtained in HCV-Tg mice.
      Suppression of HCV by Interferon-alpha 2a treatment, restored UPR responsiveness
      to ER stress tolerant cells. CONCLUSIONS: Our study shows, for the first time,
      that HCV induces adaptation to chronic ER stress which was reversed upon viral
      suppression. These finding represent a novel viral mechanism to manipulate
      cellular response pathways.

PMID- 21949744
TI  - Effects of 16 genetic variants on fasting glucose and type 2 diabetes in South
      Asians: ADCY5 and GLIS3 variants may predispose to type 2 diabetes.
AB  - BACKGROUND: The Meta-Analysis of Glucose and Insulin related traits Consortium
      (MAGIC) recently identified 16 loci robustly associated with fasting glucose,
      some of which were also associated with type 2 diabetes. The purpose of our study
      was to explore the role of these variants in South Asian populations of Punjabi
      ancestry, originating predominantly from the District of Mirpur, Pakistan.
      METHODOLOGY/PRINCIPAL FINDINGS: Sixteen single nucleotide polymorphisms (SNPs)
      were genotyped in 1678 subjects with type 2 diabetes and 1584 normoglycaemic
      controls from two Punjabi populations; one resident in the UK and one indigenous
      to the District of Mirpur. In the normoglycaemic controls investigated for
      fasting glucose associations, 12 of 16 SNPs displayed beta values with the same
      direction of effect as that seen in European studies, although only the SLC30A8
      rs11558471 SNP was nominally associated with fasting glucose (beta = 0.063 [95%
      CI: 0.013, 0.113] p = 0.015). Of interest, the MTNR1B rs10830963 SNP displayed a
      negative beta value for fasting glucose in our study; this effect size was
      significantly lower than that seen in Europeans (p = 1.29*10(-4)). In addition to
      previously reported type 2 diabetes risk variants in TCF7L2 and SLC30A8, SNPs in
      ADCY5 (rs11708067) and GLIS3 (rs7034200) displayed evidence for association with
      type 2 diabetes, with odds ratios of 1.23 (95% CI: 1.09, 1.39; p = 9.1*10(-4))
      and 1.16 (95% CI: 1.05, 1.29; p = 3.49*10(-3)) respectively.
      CONCLUSIONS/SIGNIFICANCE: Although only the SLC30A8 rs11558471 SNP was nominally
      associated with fasting glucose in our study, the finding that 12 out of 16 SNPs
      displayed a direction of effect consistent with European studies suggests that a
      number of these variants may contribute to fasting glucose variation in
      individuals of South Asian ancestry. We also provide evidence for the first time
      in South Asians that alleles of SNPs in GLIS3 and ADCY5 may confer risk of type 2
      diabetes.

PMID- 21949743
TI  - Knowledge, perceptions and information about hormone therapy (HT) among
      menopausal women: a systematic review and meta-synthesis.
AB  - BACKGROUND: The use of hormone therapy (HT) by menopausal women has declined
      since the Women's Health Initiative randomized trial (WHI) in 2002 demonstrated
      important harms associated with long-term use. However, how this information has
      influenced women's knowledge and attitudes is uncertain. We aimed to evaluate the
      attitudes and perceptions towards HT use, as well as specific concerns and
      information sources on HT since the WHI trial. METHOD/RESULTS: We did a
      systematic review to assess the attitudes and knowledge towards HT in women, and
      estimate the magnitude of the issue by pooling across the studies. Using meta
      synthesis methods, we reviewed qualitative studies and surveys and performed
      content analysis on the study reports. We pooled quantitative studies using a
      random-effects meta-analysis. We analyzed 11 qualitative studies (n = 566) and 27
      quantitative studies (n = 39251). Positive views on HT included climacteric
      symptom control, prevention of osteoporosis and a perceived improvement in
      quality of life. Negative factors reported included concerns about potential
      harmful effects, particularly cancer risks. Sources of information included
      health providers, media, and social contact. By applying a meta-synthesis
      approach we demonstrate that these findings are broadly applicable across large
      groups of patients. CONCLUSIONS: Although there are clear hazards associated with
      long-term HT use, many women view HT favorably for climacteric symptom relief.
      Media, as a source of information, is often valued as equivalent to health
      providers.

PMID- 21949746
TI  - Distinguishing characteristics between pandemic 2009-2010 influenza A (H1N1) and
      other viruses in patients hospitalized with respiratory illness.
AB  - BACKGROUND: Differences in clinical presentation and outcomes among patients
      infected with pandemic 2009 influenza A H1N1 (pH1N1) compared to other
      respiratory viruses have not been fully elucidated. METHODOLOGY/PRINCIPAL
      FINDINGS: A retrospective study was performed of all hospitalized patients at the
      peak of the pH1N1 season in whom a single respiratory virus was detected by a
      molecular assay targeting 18 viruses/subtypes (RVP, Luminex xTAG). Fifty-two
      percent (615/1192) of patients from October, 2009 to December, 2009 had a single
      respiratory virus (291 pH1N1; 207 rhinovirus; 45 RSV A/B; 37 parainfluenza; 27
      adenovirus; 6 coronavirus; and 2 metapneumovirus). No seasonal influenza A or B
      was detected. Individuals with pH1N1, compared to other viruses, were more likely
      to present with fever (92% & 70%), cough (92% & 86%), sore throat (32% & 16%),
      nausea (31% & 8%), vomiting (39% & 30%), abdominal pain (14% & 7%), and a lower
      white blood count (8,500/L & 13,600/L, all p-values<0.05). In patients with cough
      and gastrointestinal complaints, the presence of subjective fever/chills
      independently raised the likelihood of pH1N1 (OR 10). Fifty-five percent
      (336/615) of our cohort received antibacterial agents, 63% (385/615) received
      oseltamivir, and 41% (252/615) received steroids. The mortality rate of our
      cohort was 1% (7/615) and was higher in individuals with pH1N1 compared to other
      viruses (2.1% & 0.3%, respectively; p = 0.04). CONCLUSIONS/SIGNIFICANCE: During
      the peak pandemic 2009-2010 influenza season in Rhode Island, nearly half of
      patients admitted with influenza-like symptoms had respiratory viruses other than
      influenza A. A high proportion of patients were treated with antibiotics and
      pH1N1 infection had higher mortality compared to other respiratory viruses.

PMID- 21949747
TI  - Mice with different susceptibility to Japanese encephalitis virus infection show
      selective neutralizing antibody response and myeloid cell infectivity.
AB  - BACKGROUND: Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that
      causes public health problems in Asian countries. Only a limited number of JEV
      infected individuals show symptoms and develop severe encephalitis, indicating
      host-dependent susceptibilities. METHODOLOGY/PRINCIPAL FINDINGS: C3H/HeN and
      DBA/2 mice, which exhibit different mortalities when infected by intraperitoneal
      inoculation with JEV, were used as experimental models to compare viral
      pathogenesis and host responses. One hundred infectious virus particles killed
      95% of C3H/HeN mice whereas only 40% of DBA/2 mice died. JEV RNA was detected
      with similar low levels in peripheral lymphoid organs and in the sera of both
      mouse strains. High levels of viral and cytokine RNA were observed simultaneously
      in the brains of C3H/HeN and DBA/2 mice starting on days 6 and 9 post-infection,
      respectively. The kinetics of the cytokines in sera correlated with the viral
      replication in the brain. Significantly earlier and higher titers of neutralizing
      antibodies were detected in the DBA/2 strain. Primary embryonic fibroblasts, bone
      marrow-derived dendritic cells and macrophages from the two mouse strains were
      cultured. Fibroblasts displayed similar JEV replication abilities, whereas DBA/2
      derived myeloid antigen-presenting cells had lower viral infectivity and
      production compared to the C3H/HeN-derived cells. CONCLUSIONS/SIGNIFICANCE: Mice
      with different susceptibilities to JEV neuroinvasion did not show changes in
      viral tropism and host innate immune responses prior to viral entry into the
      central nervous system. However, early and high neutralizing antibody responses
      may be crucial for preventing viral neuroinvasion and host fatality. In addition,
      low permissiveness of myeloid dendritic cells and macrophages to JEV infection in
      vitro may be elements associated with late and decreased mouse neuroinvasion.

PMID- 21949748
TI  - A strawberry KNOX gene regulates leaf, flower and meristem architecture.
AB  - The KNOTTED-LIKE HOMEODOMAIN (KNOX) genes play a central role in maintenance of
      the shoot apical meristem. They also contribute to the morphology of simple and
      compound leaves. In this report we characterize the FaKNOX1 gene from strawberry
      (Fragaria spp.) and demonstrate its function in trasgenic plants. The FaKNOX1
      cDNA was isolated from a cultivated strawberry (F.*ananassa) flower EST library.
      The sequence is most similar to Class I KNOX genes, and was mapped to linkage
      group VI of the diploid strawberry genome. Unlike most KNOX genes studied, steady
      state transcript levels were highest in flowers and fruits. Transcripts were also
      detected in emerging leaf primordia and the apical dome. Transgenic strawberry
      plants suppressing or overexpressing FaKNOX1 exhibited conspicuous changes in
      plant form. The FaKNOX1 RNAi plants presented a dwarfed phenotype with deeply
      serrated leaflets and exaggerated petiolules. They also exhibited a high level of
      cellular disorganization of the shoot apical meristem and leaves. Overexpression
      of FaKNOX1 caused dwarfed stature with wrinkled leaves. These gain- and loss-of
      function assays in strawberry functionally demonstrate the contributions of a
      KNOX domain protein in a rosaceous species.

PMID- 21949749
TI  - Discovery of DNA viruses in wild-caught mosquitoes using small RNA high
      throughput sequencing.
AB  - BACKGROUND: Mosquito-borne infectious diseases pose a severe threat to public
      health in many areas of the world. Current methods for pathogen detection and
      surveillance are usually dependent on prior knowledge of the etiologic agents
      involved. Hence, efficient approaches are required for screening wild mosquito
      populations to detect known and unknown pathogens. METHODOLOGY/PRINCIPAL
      FINDINGS: In this study, we explored the use of Next Generation Sequencing to
      identify viral agents in wild-caught mosquitoes. We extracted total RNA from
      different mosquito species from South China. Small 18-30 bp length RNA molecules
      were purified, reverse-transcribed into cDNA and sequenced using Illumina GAIIx
      instrumentation. Bioinformatic analyses to identify putative viral agents were
      conducted and the results confirmed by PCR. We identified a non-enveloped single
      stranded DNA densovirus in the wild-caught Culex pipiens molestus mosquitoes. The
      majority of the viral transcripts (.>80% of the region) were covered by the small
      viral RNAs, with a few peaks of very high coverage obtained. The +/- strand
      sequence ratio of the small RNAs was approximately 7?1, indicating that the
      molecules were mainly derived from the viral RNA transcripts. The small viral
      RNAs overlapped, enabling contig assembly of the viral genome sequence. We
      identified some small RNAs in the reverse repeat regions of the viral 5'- and 3' 
      untranslated regions where no transcripts were expected.
      CONCLUSIONS/SIGNIFICANCE: Our results demonstrate for the first time that high
      throughput sequencing of small RNA is feasible for identifying viral agents in
      wild-caught mosquitoes. Our results show that it is possible to detect DNA
      viruses by sequencing the small RNAs obtained from insects, although the
      underlying mechanism of small viral RNA biogenesis is unclear. Our data and those
      of other researchers show that high throughput small RNA sequencing can be used
      for pathogen surveillance in wild mosquito vectors.

PMID- 21949745
TI  - First transcriptome of the testis-vas deferens-male accessory gland and proteome
      of the spermatophore from Dermacentor variabilis (Acari: Ixodidae).
AB  - Ticks are important vectors of numerous human diseases and animal diseases.
      Feeding stimulates spermatogenesis, mating and insemination of male factors that
      trigger female reproduction. The physiology of male reproduction and its
      regulation of female development are essentially a black box. Several
      transcriptomes have catalogued expression of tick genes in the salivary glands,
      synganglion and midgut but no comprehensive investigation has addressed male
      reproduction and mating. Consequently, a new global approach using
      transcriptomics, proteomics, and quantitative gene expression is needed to
      understand male reproduction and stimulation of female reproduction.This first
      transcriptome to the reproductive biology of fed male ticks, Dermacentor
      variabilis, was obtained by 454 pyrosequencing (563,093 reads, 12,804 contigs).
      Gene Ontology (Biological Processes level III) recognized 3,866 transcripts in 73
      different categories; spermiogenesis; spermatogenesis; peptidases, lipases and
      hydrolases; oxidative and environmental stress; immune defense; and protein
      binding. Reproduction-associated genes included serine/threonine kinase,
      metalloendoproteinases, ferritins, serine proteases, trypsin, cysteine proteases,
      serpins, a cystatin, GPCR and others. qRT-PCR showed significant upregulation
      from unfed versus fed adult male reproductive organs of zinc metalloprotease,
      astacin metalloprotease and serine protease, enzymes important in spermiogenesis
      and mating activity in insects, as well as a GPCR with the greatest similarity to
      a SIFamide receptor known to be important in regulating courtship behavior in
      Drosophila. Proteomics on these organs and the spermatophore by tryptic
      digestion/Liquid chromatography/Mass spectrometry/Mass spectrometry (LC/MS/MS)
      demonstrated expression of many of the same messages found by 454 sequencing,
      supporting their identification, and revealed differences in protein distribution
      in the reproductive system versus the spermatophore. We found Efalpha but no EF
      beta in the transcriptome and neither of these proteins in the spermatophore.
      Thus, the previously described model for male regulation of female reproduction
      may not apply to other ticks. A new paradigm is needed to explain male
      stimulation of female tick reproduction.

PMID- 21949750
TI  - Noninvasive assessment of antenatal hydronephrosis in mice reveals a critical
      role for Robo2 in maintaining anti-reflux mechanism.
AB  - Antenatal hydronephrosis and vesicoureteral reflux (VUR) are common renal tract
      birth defects. We recently showed that disruption of the Robo2 gene is associated
      with VUR in humans and antenatal hydronephrosis in knockout mice. However, the
      natural history, causal relationship and developmental origins of these clinical
      conditions remain largely unclear. Although the hydronephrosis phenotype in Robo2
      knockout mice has been attributed to the coexistence of ureteral reflux and
      obstruction in the same mice, this hypothesis has not been tested experimentally.
      Here we used noninvasive high-resolution micro-ultrasonography and pathological
      analysis to follow the progression of antenatal hydronephrosis in individual
      Robo2-deficient mice from embryo to adulthood. We found that hydronephrosis
      progressed continuously after birth with no spontaneous resolution. With the use
      of a microbubble ultrasound contrast agent and ultrasound-guided percutaneous
      aspiration, we demonstrated that antenatal hydronephrosis in Robo2-deficient mice
      is caused by high-grade VUR resulting from a dilated and incompetent
      ureterovesical junction rather than ureteral obstruction. We further documented
      Robo2 expression around the developing ureterovesical junction and identified
      early dilatation of ureteral orifice structures as a potential fetal origin of
      antenatal hydronephrosis and VUR. Our results thus demonstrate that Robo2 is
      crucial for the formation of a normal ureteral orifice and for the maintenance of
      an effective anti-reflux mechanism. This study also establishes a reproducible
      genetic mouse model of progressive antenatal hydronephrosis and primary high
      grade VUR.

PMID- 21949751
TI  - Impacts of poultry house environment on poultry litter bacterial community
      composition.
AB  - Viral and bacterial pathogens are a significant economic concern to the US
      broiler industry and the ecological epicenter for poultry pathogens is the
      mixture of bedding material, chicken excrement and feathers that comprises the
      litter of a poultry house. This study used high-throughput sequencing to assess
      the richness and diversity of poultry litter bacterial communities, and to look
      for connections between these communities and the environmental characteristics
      of a poultry house including its history of gangrenous dermatitis (GD). Cluster
      analysis of 16S rRNA gene sequences revealed differences in the distribution of
      bacterial phylotypes between Wet and Dry litter samples and between houses. Wet
      litter contained greater diversity with 90% of total bacterial abundance
      occurring within the top 214 OTU clusters. In contrast, only 50 clusters
      accounted for 90% of Dry litter bacterial abundance. The sixth largest OTU
      cluster across all samples classified as an Arcobacter sp., an emerging human
      pathogen, occurring in only the Wet litter samples of a house with a modern
      evaporative cooling system. Ironically, the primary pathogenic clostridial and
      staphylococcal species associated with GD were not found in any house; however,
      there were thirteen 16S rRNA gene phylotypes of mostly gram-positive phyla that
      were unique to GD-affected houses and primarily occurred in Wet litter samples.
      Overall, the poultry house environment appeared to substantially impact the
      composition of litter bacterial communities and may play a key role in the
      emergence of food-borne pathogens.

PMID- 21949752
TI  - Structure and molecular evolution of CDGSH iron-sulfur domains.
AB  - The recently discovered CDGSH iron-sulfur domains (CISDs) are classified into
      seven major types with a wide distribution throughout the three domains of life.
      The type 1 protein mitoNEET has been shown to fold into a dimer with the
      signature CDGSH motif binding to a [2Fe-2S] cluster. However, the structures of
      all other types of CISDs were unknown. Here we report the crystal structures of
      type 3, 4, and 6 CISDs determined at 1.5 A, 1.8 A and 1.15 A resolution,
      respectively. The type 3 and 4 CISD each contain one CDGSH motif and adopt a
      dimeric structure. Although similar to each other, the two structures have
      permutated topologies, and both are distinct from the type 1 structure. The type
      6 CISD contains tandem CDGSH motifs and adopts a monomeric structure with an
      internal pseudo dyad symmetry. All currently known CISD structures share dual
      iron-sulfur binding modules and a beta-sandwich for either intermolecular or
      intramolecular dimerization. The iron-sulfur binding module, the beta-strand N
      terminal to the module and a proline motif are conserved among different type
      structures, but the dimerization module and the interface and orientation between
      the two iron-sulfur binding modules are divergent. Sequence analysis further
      shows resemblance between CISD types 4 and 7 and between 1 and 2. Our findings
      suggest that all CISDs share common ancestry and diverged into three primary
      folds with a characteristic phylogenetic distribution: a eukaryote-specific fold
      adopted by types 1 and 2 proteins, a prokaryote-specific fold adopted by types 3,
      4 and 7 proteins, and a tandem-motif fold adopted by types 5 and 6 proteins. Our
      comprehensive structural, sequential and phylogenetic analysis provides
      significant insight into the assembly principles and evolutionary relationship of
      CISDs.

PMID- 21949753
TI  - Modeling fractal structure of city-size distributions using correlation
      functions.
AB  - Zipf's law is one the most conspicuous empirical facts for cities, however, there
      is no convincing explanation for the scaling relation between rank and size and
      its scaling exponent. Using the idea from general fractals and scaling, I propose
      a dual competition hypothesis of city development to explain the value intervals
      and the special value, 1, of the power exponent. Zipf's law and Pareto's law can
      be mathematically transformed into one another, but represent different processes
      of urban evolution, respectively. Based on the Pareto distribution, a frequency
      correlation function can be constructed. By scaling analysis and multifractals
      spectrum, the parameter interval of Pareto exponent is derived as (0.5, 1]; Based
      on the Zipf distribution, a size correlation function can be built, and it is
      opposite to the first one. By the second correlation function and multifractals
      notion, the Pareto exponent interval is derived as [1, 2). Thus the process of
      urban evolution falls into two effects: one is the Pareto effect indicating city
      number increase (external complexity), and the other the Zipf effect indicating
      city size growth (internal complexity). Because of struggle of the two effects,
      the scaling exponent varies from 0.5 to 2; but if the two effects reach
      equilibrium with each other, the scaling exponent approaches 1. A series of
      mathematical experiments on hierarchical correlation are employed to verify the
      models and a conclusion can be drawn that if cities in a given region follow
      Zipf's law, the frequency and size correlations will follow the scaling law. This
      theory can be generalized to interpret the inverse power-law distributions in
      various fields of physical and social sciences.

PMID- 21949754
TI  - Polymorphism in Gag gene cleavage sites of HIV-1 non-B subtype and virological
      outcome of a first-line lopinavir/ritonavir single drug regimen.
AB  - Virological failure on a boosted-protease inhibitor (PI/r) first-line triple
      combination is usually not associated with the detection of resistance mutations
      in the protease gene. Thus, other resistance pathways are being investigated.
      First-line PI/r monotherapy is the best model to investigate in vivo if the
      presence of mutations in the cleavage sites (CS) of gag gene prior to any
      antiretroviral treatment might influence PI/r efficacy. 83 patients were assigned
      to initiate antiretroviral treatment with first-line lopinavir/r monotherapy in
      the randomised Monark trial. We compared baseline sequence of gag CS between
      patients harbouring B or non-B HIV-1 subtype, and between those who achieved
      viral suppression and those who experienced virological failure while on LPV/r
      monotherapy up to Week 96. Baseline sequence of gag CS was available for 82/83
      isolates; 81/82 carried at least one substitution in gag CS compared to HXB2
      sequence. At baseline, non-B subtype isolates were significantly more likely to
      harbour mutations in gag CS than B subtype isolates (p<0.0001). Twenty-three
      patients experienced virological failure while on lopinavir/r monotherapy. The
      presence of more than two substitutions in p2/NC site at baseline significantly
      predicted virological failure (p = 0.0479), non-B subtype isolates being more
      likely to harbour more than two substitutions in this specific site. In
      conclusion, gag cleavage site was highly polymorphic in antiretroviral-naive
      patients harbouring a non-B HIV-1 strain. We show that pre-therapy mutations in
      gag cleavage site sequence were significantly associated with the virological
      outcome of a first-line LPV/r single drug regimen in the Monark trial.

PMID- 21949755
TI  - Present limits to heat-adaptability in corals and population-level responses to
      climate extremes.
AB  - Climate change scenarios suggest an increase in tropical ocean temperature by 1-3
      degrees C by 2099, potentially killing many coral reefs. But Arabian/Persian Gulf
      corals already exist in this future thermal environment predicted for most
      tropical reefs and survived severe bleaching in 2010, one of the hottest years on
      record. Exposure to 33-35 degrees C was on average twice as long as in non
      bleaching years. Gulf corals bleached after exposure to temperatures above 34
      degrees C for a total of 8 weeks of which 3 weeks were above 35 degrees C. This
      is more heat than any other corals can survive, providing an insight into the
      present limits of holobiont adaptation. We show that average temperatures as well
      as heat-waves in the Gulf have been increasing, that coral population levels will
      fluctuate strongly, and reef-building capability will be compromised. This, in
      combination with ocean acidification and significant local threats posed by
      rampant coastal development puts even these most heat-adapted corals at risk. WWF
      considers the Gulf ecoregion as "critically endangered". We argue here that Gulf
      corals should be considered for assisted migration to the tropical Indo-Pacific.
      This would have the double benefit of avoiding local extinction of the world's
      most heat-adapted holobionts while at the same time introducing their genetic
      information to populations naive to such extremes, potentially assisting their
      survival. Thus, the heat-adaptation acquired by Gulf corals over 6 k, could
      benefit tropical Indo-Pacific corals who have <100 y until they will experience a
      similarly harsh climate. Population models suggest that the heat-adapted corals
      could become dominant on tropical reefs within ~20 years.

PMID- 21949756
TI  - Inhibition of HIV-1 infection in ex vivo cervical tissue model of human vagina by
      palmitic acid; implications for a microbicide development.
AB  - BACKGROUND: Approximately 80% of all new HIV-1 infections are acquired through
      sexual contact. Currently, there is no clinically approved microbicide,
      indicating a clear and urgent therapeutic need. We recently reported that
      palmitic acid (PA) is a novel and specific inhibitor of HIV-1 fusion and entry.
      Mechanistically, PA inhibits HIV-1 infection by binding to a novel pocket on the
      CD4 receptor and blocks efficient gp120-to-CD4 attachment. Here, we wanted to
      assess the ability of PA to inhibit HIV-1 infection in cervical tissue ex vivo
      model of human vagina, and determine its effect on Lactobacillus (L) species of
      probiotic vaginal flora. PRINCIPAL FINDINGS: Our results show that treatment with
      100-200 uM PA inhibited HIV-1 infection in cervical tissue by up to 50%, and this
      treatment was not toxic to the tissue or to L. crispatus and jensenii species of
      vaginal flora. In vitro, in a cell free system that is independent of in vivo
      cell associated CD4 receptor; we determined inhibition constant (Ki) to be ~2.53
      uM. SIGNIFICANCE: These results demonstrate utility of PA as a model molecule for
      further preclinical development of a safe and potent HIV-1 entry microbicide
      inhibitor.

PMID- 21949757
TI  - N-acetylcysteine increases the frequency of bone marrow pro-B/pre-B cells, but
      does not reverse cigarette smoking-induced loss of this subset.
AB  - BACKGROUND: We previously showed that mice exposed to cigarette smoke for three
      weeks exhibit loss of bone marrow B cells at the Pro-B-to-pre-B cell transition,
      but the reason for this is unclear. The antioxidant N-acetylcysteine (NAC), a
      glutathione precursor, has been used as a chemopreventive agent to reduce adverse
      effects of cigarette smoke exposure on lung function. Here we determined whether
      smoke exposure impairs B cell development by inducing cell cycle arrest or
      apoptosis, and whether NAC treatment prevents smoking-induced loss of developing
      B cells. METHODOLOGY/PRINCIPAL FINDINGS: Groups of normal mice were either
      exposed to filtered room air or cigarette smoke with or without concomitant NAC
      treatment for 5 days/week for three weeks. Bone marrow B cell developmental
      subsets were enumerated, and sorted pro-B (B220(+)CD43(+)) and pre-B
      (B220(+)CD43(-)) cell fractions were analyzed for cell cycle status and the
      percentage of apoptotic cells. We find that, compared to sham controls, smoke
      exposed mice have ~60% fewer pro-B/pre-B cells, regardless of NAC treatment.
      Interestingly, NAC-treated mice show a 21-38% increase in total bone marrow
      cellularity and lymphocyte frequency and about a 2-fold increase in the pro-B/pre
      B cell subset, compared to sham-treated controls. No significant smoking- or NAC
      dependent differences were detected in frequency of apoptotic cells or the
      percentage cells in the G1, S, or G2 phases of the cycle.
      CONCLUSIONS/SIGNIFICANCE: The failure of NAC treatment to prevent smoking-induced
      loss of bone marrow pre-B cells suggests that oxidative stress is not directly
      responsible for this loss. The unexpected expansion of the pro-B/pre-B cell
      subset in response to NAC treatment suggests oxidative stress normally
      contributes to cell loss at this developmental stage, and also reveals a
      potential side effect of therapeutic administration of NAC to prevent smoking
      induced loss of lung function.

PMID- 21949759
TI  - Rapid genotyping of soybean cultivars using high throughput sequencing.
AB  - Soybean (Glycine max) breeding involves improving commercially grown varieties by
      introgressing important agronomic traits from poor yielding accessions and/or
      wild relatives of soybean while minimizing the associated yield drag. Molecular
      markers associated with these traits are instrumental in increasing the
      efficiency of producing such crosses and Single Nucleotide Polymorphisms (SNPs)
      are particularly well suited for this task, owing to high density in the non
      genic regions and thus increased likelihood of finding a tightly linked marker to
      a given trait. A rapid method to develop SNP markers that can differentiate
      specific loci between any two parents in soybean is thus highly desirable. In
      this study we investigate such a protocol for developing SNP markers between
      multiple soybean accessions and the reference Williams 82 genome. To restrict
      sampling frequency reduced representation libraries (RRLs) of genomic DNA were
      generated by restriction digestion followed by library construction. We chose to
      sequence four accessions Dowling (PI 548663), Dwight (PI 597386), Komata
      (PI200492) and PI 594538A for their agronomic importance as well as Williams 82
      as a control.MseI was chosen to digest genomic DNA based on predictions that it
      will cut sparingly in the mathematically defined high-copy-number regions of the
      genome. All RRLs were sequenced on the Illumina genome analyzer. Reads were
      aligned to the Glyma1 reference assembly and SNP calls made from the alignments.
      We identified from 4294 to 14550 SNPs between the four accessions and the
      Williams 82 reference. In addition a small number of SNPs (1142) were found by
      aligning Williams 82 reads to the reference assembly (Glyma1) suggesting limited
      genetic variation within the Williams 82 line. The SNP data allowed us to
      estimate genetic diversity between the four lines and Williams 82. Restriction
      digestion of soybean genomic DNA with MseI followed by high throughput sequencing
      provides a rapid and reproducible method for generating SNP markers.

PMID- 21949758
TI  - Biological effects of a de novo designed myxoma virus peptide analogue:
      evaluation of cytotoxicity on tumor cells.
AB  - BACKGROUND: The Resonant Recognition Model (RRM) is a physico-mathematical model
      that interprets protein sequence linear information using digital signal
      processing methods. In this study the RRM concept was employed for structure
      function analysis of myxoma virus (MV) proteins and the design of a short
      bioactive therapeutic peptide with MV-like antitumor/cytotoxic activity.
      METHODOLOGY/PRINCIPAL FINDINGS: The analogue RRM-MV was designed by RRM as a
      linear 18 aa 2.3 kDa peptide. The biological activity of this computationally
      designed peptide analogue against cancer and normal cell lines was investigated.
      The cellular cytotoxicity effects were confirmed by confocal immunofluorescence
      microscopy, by measuring the levels of cytoplasmic lactate dehydrogenase (LDH)
      and by Prestoblue cell viability assay for up to 72 hours in peptide treated and
      non-treated cell cultures. Our results revealed that RRM-MV induced a significant
      dose and time-dependent cytotoxic effect on murine and human cancer cell lines.
      Yet, when normal murine cell lines were similarly treated with RRM-MV, no
      cytotoxic effects were observed. Furthermore, the non-bioactive RRM designed
      peptide RRM-C produced negligible cytotoxic effects on these cancer and normal
      cell lines when used at similar concentrations. The presence/absence of
      phosphorylated Akt activity in B16F0 mouse melanoma cells was assessed to
      indicate the possible apoptosis signalling pathway that could be affected by the
      peptide treatment. So far, Akt activity did not seem to be significantly affected
      by RRM-MV as is the case for the original viral protein.
      CONCLUSIONS/SIGNIFICANCE: Our findings indicate the successful application of the
      RRM concept to design a bioactive peptide analogue (RRM-MV) with cytotoxic
      effects on tumor cells only. This 2.345 kDa peptide analogue to a 49 kDa viral
      protein may be suitable to be developed as a potential cancer therapeutic. These
      results also open a new direction to the rational design of therapeutic agents
      for future cancer treatment.

PMID- 21949760
TI  - Rac1 and Rac3 GTPases regulate the development of hilar mossy cells by affecting
      the migration of their precursors to the hilus.
AB  - We have previously shown that double deletion of the genes for Rac1 and Rac3
      GTPases during neuronal development affects late developmental events that
      perturb the circuitry of the hippocampus, with ensuing epileptic phenotype. These
      effects include a defect in mossy cells, the major class of excitatory neurons of
      the hilus. Here, we have addressed the mechanisms that affect the loss of hilar
      mossy cells in the dorsal hippocampus of mice depleted of the two Rac GTPases.
      Quantification showed that the loss of mossy cells was evident already at
      postnatal day 8, soon after these cells become identifiable by a specific marker
      in the dorsal hilus. Comparative analysis of the hilar region from control and
      double mutant mice revealed that synaptogenesis was affected in the double
      mutants, with strongly reduced presynaptic input from dentate granule cells. We
      found that apoptosis was equally low in the hippocampus of both control and
      double knockout mice. Labelling with bromodeoxyuridine at embryonic day 12.5
      showed no evident difference in the proliferation of neuronal precursors in the
      hippocampal primordium, while differences in the number of bromodeoxyuridine
      labelled cells in the developing hilus revealed a defect in the migration of
      immature, developing mossy cells in the brain of double knockout mice. Overall,
      our data show that Rac1 and Rac3 GTPases participate in the normal development of
      hilar mossy cells, and indicate that they are involved in the regulation of the
      migration of the mossy cell precursor by preventing their arrival to the dorsal
      hilus.

PMID- 21949761
TI  - Dicer is required for haploid male germ cell differentiation in mice.
AB  - BACKGROUND: The RNase III endonuclease Dicer is an important regulator of gene
      expression that processes microRNAs (miRNAs) and small interfering RNAs (siRNAs).
      The best-characterized function of miRNAs is gene repression at the post
      transcriptional level through the pairing with mRNAs of protein-encoding genes.
      Small RNAs can also act at the transcriptional level by controlling the
      epigenetic status of chromatin. Dicer and other mediators of small RNA pathways
      are present in mouse male germ cells, and several miRNAs and endogenous siRNAs
      are expressed in the testis, suggesting that Dicer-dependent small RNAs are
      involved in the control of the precisely timed and highly organised process of
      spermatogenesis. PRINCIPAL FINDINGS: Being interested in the Dicer-mediated
      functions during spermatogenesis, we have analysed here a male germ cell-specific
      Dicer1 knockout mouse model, in which the deletion of Dicer1 takes place during
      early postnatal development in spermatogonia. We found that Dicer1 knockout
      testes were reduced in size and spermatogenesis within the seminiferous tubules
      was disrupted. Dicer1 knockout epididymides contained very low number of mature
      sperm with pronounced morphological abnormalities. Spermatogonial differentiation
      appeared unaffected. However, the number of haploid cells was decreased in
      knockout testes, and an increased number of apoptotic spermatocytes was observed.
      The most prominent defects were found during late haploid differentiation, and
      Dicer was demonstrated to be critical for the normal organization of chromatin
      and nuclear shaping of elongating spermatids. CONCLUSIONS/SIGNIFICANCE: We
      demonstrate that Dicer and Dicer-dependent small RNAs are imperative regulators
      of haploid spermatid differentiation and essential for male fertility.

PMID- 21949762
TI  - Co-crystal structures of inhibitors with MRCKbeta, a key regulator of tumor cell
      invasion.
AB  - MRCKalpha and MRCKbeta (myotonic dystrophy kinase-related Cdc42-binding kinases)
      belong to a subfamily of Rho GTPase activated serine/threonine kinases within the
      AGC-family that regulate the actomyosin cytoskeleton. Reflecting their roles in
      myosin light chain (MLC) phosphorylation, MRCKalpha and MRCKbeta influence cell
      shape and motility. We report further evidence for MRCKalpha and MRCKbeta
      contributions to the invasion of cancer cells in 3-dimensional matrix invasion
      assays. In particular, our results indicate that the combined inhibition of
      MRCKalpha and MRCKbeta together with inhibition of ROCK kinases results in
      significantly greater effects on reducing cancer cell invasion than blocking
      either MRCK or ROCK kinases alone. To probe the kinase ligand pocket, we screened
      159 kinase inhibitors in an in vitro MRCKbeta kinase assay and found 11 compounds
      that inhibited enzyme activity >80% at 3 uM. Further analysis of three hits, Y
      27632, Fasudil and TPCA-1, revealed low micromolar IC(50) values for MRCKalpha
      and MRCKbeta. We also describe the crystal structure of MRCKbeta in complex with
      inhibitors Fasudil and TPCA-1 bound to the active site of the kinase. These high
      resolution structures reveal a highly conserved AGC kinase fold in a typical
      dimeric arrangement. The kinase domain is in an active conformation with a fully
      ordered and correctly positioned alphaC helix and catalytic residues in a
      conformation competent for catalysis. Together, these results provide further
      validation for MRCK involvement in regulation of cancer cell invasion and present
      a valuable starting point for future structure-based drug discovery efforts.

PMID- 21949763
TI  - A hidden Markov model for analysis of frontline veterinary data for emerging
      zoonotic disease surveillance.
AB  - Surveillance systems tracking health patterns in animals have potential for early
      warning of infectious disease in humans, yet there are many challenges that
      remain before this can be realized. Specifically, there remains the challenge of
      detecting early warning signals for diseases that are not known or are not part
      of routine surveillance for named diseases. This paper reports on the development
      of a hidden Markov model for analysis of frontline veterinary sentinel
      surveillance data from Sri Lanka. Field veterinarians collected data on syndromes
      and diagnoses using mobile phones. A model for submission patterns accounts for
      both sentinel-related and disease-related variability. Models for commonly
      reported cattle diagnoses were estimated separately. Region-specific weekly
      average prevalence was estimated for each diagnoses and partitioned into normal
      and abnormal periods. Visualization of state probabilities was used to indicate
      areas and times of unusual disease prevalence. The analysis suggests that hidden
      Markov modelling is a useful approach for surveillance datasets from novel
      populations and/or having little historical baselines.

PMID- 21949764
TI  - A single heterochromatin boundary element imposes position-independent
      antisilencing activity in Saccharomyces cerevisiae minichromosomes.
AB  - Chromatin boundary elements serve as cis-acting regulatory DNA signals required
      to protect genes from the effects of the neighboring heterochromatin. In the
      yeast genome, boundary elements act by establishing barriers for heterochromatin
      spreading and are sufficient to protect a reporter gene from transcriptional
      silencing when inserted between the silencer and the reporter gene. Here we
      dissected functional topography of silencers and boundary elements within
      circular minichromosomes in Saccharomyces cerevisiae. We found that both HML-E
      and HML-I silencers can efficiently repress the URA3 reporter on a multi-copy
      yeast minichromosome and we further showed that two distinct heterochromatin
      boundary elements STAR and TEF2-UASrpg are able to limit the heterochromatin
      spreading in circular minichromosomes. In surprising contrast to what had been
      observed in the yeast genome, we found that in minichromosomes the
      heterochromatin boundary elements inhibit silencing of the reporter gene even
      when just one boundary element is positioned at the distal end of the URA3
      reporter or upstream of the silencer elements. Thus the STAR and TEF2-UASrpg
      boundary elements inhibit chromatin silencing through an antisilencing activity
      independently of their position or orientation in S. cerevisiae minichromosomes
      rather than by creating a position-specific barrier as seen in the genome. We
      propose that the circular DNA topology facilitates interactions between the
      boundary and silencing elements in the minichromosomes.

PMID- 21949765
TI  - Asymmetrical gene flow in a hybrid zone of Hawaiian Schiedea (Caryophyllaceae)
      species with contrasting mating systems.
AB  - Asymmetrical gene flow, which has frequently been documented in naturally
      occurring hybrid zones, can result from various genetic and demographic factors.
      Understanding these factors is important for determining the ecological
      conditions that permitted hybridization and the evolutionary potential inherent
      in hybrids. Here, we characterized morphological, nuclear, and chloroplast
      variation in a putative hybrid zone between Schiedea menziesii and S. salicaria,
      endemic Hawaiian species with contrasting breeding systems. Schiedea menziesii is
      hermaphroditic with moderate selfing; S. salicaria is gynodioecious and wind
      pollinated, with partially selfing hermaphrodites and largely outcrossed females.
      We tested three hypotheses: 1) putative hybrids were derived from natural crosses
      between S. menziesii and S. salicaria, 2) gene flow via pollen is unidirectional
      from S. salicaria to S. menziesii and 3) in the hybrid zone, traits associated
      with wind pollination would be favored as a result of pollen-swamping by S.
      salicaria. Schiedea menziesii and S. salicaria have distinct morphologies and
      chloroplast genomes but are less differentiated at the nuclear loci. Hybrids are
      most similar to S. menziesii at chloroplast loci, exhibit nuclear allele
      frequencies in common with both parental species, and resemble S. salicaria in
      pollen production and pollen size, traits important to wind pollination.
      Additionally, unlike S. menziesii, the hybrid zone contains many females,
      suggesting that the nuclear gene responsible for male sterility in S. salicaria
      has been transferred to hybrid plants. Continued selection of nuclear genes in
      the hybrid zone may result in a population that resembles S. salicaria, but
      retains chloroplast lineage(s) of S. menziesii.

PMID- 21949766
TI  - Sub-typing of rheumatic diseases based on a systems diagnosis questionnaire.
AB  - BACKGROUND: The future of personalized medicine depends on advanced diagnostic
      tools to characterize responders and non-responders to treatment. Systems
      diagnosis is a new approach which aims to capture a large amount of symptom
      information from patients to characterize relevant sub-groups. METHODOLOGY: 49
      patients with a rheumatic disease were characterized using a systems diagnosis
      questionnaire containing 106 questions based on Chinese and Western medicine
      symptoms. Categorical principal component analysis (CATPCA) was used to discover
      differences in symptom patterns between the patients. Two Chinese medicine
      experts where subsequently asked to rank the Cold and Heat status of all the
      patients based on the questionnaires. These rankings were used to study the Cold
      and Heat symptoms used by these practitioners. FINDINGS: The CATPCA analysis
      results in three dimensions. The first dimension is a general factor (40.2%
      explained variance). In the second dimension (12.5% explained variance)
      'anxious', 'worrying', 'uneasy feeling' and 'distressed' were interpreted as the
      Internal disease stage, and 'aggravate in wind', 'fear of wind' and 'aversion to
      cold' as the External disease stage. In the third dimension (10.4% explained
      variance) 'panting s', 'superficial breathing', 'shortness of breath s',
      'shortness of breath f' and 'aversion to cold' were interpreted as Cold and
      'restless', 'nervous', 'warm feeling', 'dry mouth s' and 'thirst' as Heat
      related. 'Aversion to cold', 'fear of wind' and 'pain aggravates with cold' are
      most related to the experts Cold rankings and 'aversion to heat', 'fullness of
      chest' and 'dry mouth' to the Heat rankings. CONCLUSIONS: This study shows that
      the presented systems diagnosis questionnaire is able to identify groups of
      symptoms that are relevant for sub-typing patients with a rheumatic disease.

PMID- 21949767
TI  - Simultaneous inhibition of mTOR-containing complex 1 (mTORC1) and MNK induces
      apoptosis of cutaneous T-cell lymphoma (CTCL) cells.
AB  - BACKGROUND: mTOR kinase forms the mTORC1 complex by associating with raptor and
      other proteins and affects a number of key cell functions. mTORC1 activates
      p70S6kinase 1 (p70S6K1) and inhibits 4E-binding protein 1 (4E-BP1). In turn,
      p70S6K1 phosphorylates a S6 protein of the 40S ribosomal subunit (S6rp) and 4E
      BP1, with the latter negatively regulating eukaryotic initiation factor 4E (eIF
      4E). MNK1 and MNK2 kinases phosphorylate and augment activity of eIF4E. Rapamycin
      and its analogs are highly specific, potent, and relatively non-toxic inhibitors
      of mTORC1. Although mTORC1 activation is present in many types of malignancies,
      rapamycin-type inhibitors shows relatively limited clinical efficacy as single
      agents. Initially usually indolent, CTCL displays a tendency to progress to the
      aggressive forms with limited response to therapy and poor prognosis. Our
      previous study (M. Marzec et al. 2008) has demonstrated that CTCL cells display
      mTORC1 activation and short-term treatment of CTCL-derived cells with rapamycin
      suppressed their proliferation and had little effect on the cell survival.
      METHODS: Cells derived from CTCL were treated with mTORC1 inhibitor rapamycin and
      MNK inhibitor and evaluated for inhibition of the mTORC1 signaling pathway and
      cell growth and survival. RESULTS: Whereas the treatment with rapamycin
      persistently inhibited mTORC1 signaling, it suppressed only partially the cell
      growth. MNK kinase mediated the eIF4E phosphorylation and inhibition or depletion
      of MNK markedly suppressed proliferation of the CTCL cells when combined with the
      rapamycin-mediated inhibition of mTORC1. While MNK inhibition alone mildly
      suppressed the CTCL cell growth, the combined MNK and mTORC1 inhibition totally
      abrogated the growth. Similarly, MNK inhibitor alone displayed a minimal pro
      apoptotic effect; in combination with rapamycin it triggered profound cell
      apoptosis. CONCLUSIONS: These findings indicate that the combined inhibition of
      mTORC1 and MNK may prove beneficial in the treatment of CTCL and other
      malignancies.

PMID- 21949768
TI  - Involvement of CCR6/CCL20/IL-17 axis in NSCLC disease progression.
AB  - OBJECTIVES: Autocrine and paracrine chemokine/chemokine receptor-based
      interactions promote non-small-cell-lung-cancer (NSCLC) carcinogenesis.
      CCL20/CCR6 interactions are involved in prostatic and colonic malignancy
      pathogenesis. The expression and function of CCL20/CCR6 and its related Th-17
      type immune response in NSCLC is not yet defined. We sought to characterize the
      role of the CCL20/CCR6/IL-17 axis in NSCLC tumor growth. METHODS: A specialized
      histopathologist blindly assessed CCL20/CCR6 expression levels in 49 tissue
      samples of NSCLC patients operated in our department. Results were correlated to
      disease progression. Colony assays, ERK signaling and chemokine production were
      measured to assess cancer cell responsiveness to CCL20 and IL-17 stimulation.
      RESULTS: CCL20 was highly expressed in the majority (38/49, 77.5%) of tumor
      samples. Only a minority of samples (8/49, 16.5%) showed high CCR6 expression.
      High CCR6 expression was associated with a shorter disease-free survival (P =
      0.008) and conferred a disease stage-independent 4.87-fold increased risk for
      disease recurrence (P = 0.0076, CI 95% 1.52-15.563). Cancerous cell colony
      forming capacity was increased by CCL20 stimulation; this effect was dependent in
      part on ERK phosphorylation and signaling. IL-17 expression was detected in
      NSCLC; IL-17 potentiated the production of CCL20 by cancerous cells. CONCLUSION:
      Our findings suggest that the CCL20/CCR6 axis promotes NSCLC disease progression.
      CCR6 is identified as a potential new prognostic marker and the CCL20/CCR6/IL-17
      axis as a potential new therapeutic target. Larger scale studies are required to
      consolidate these observations.

PMID- 21949769
TI  - Tactile motion and pattern processing assessed with high-field FMRI.
AB  - Processing of motion and pattern has been extensively studied in the visual
      domain, but much less in the somatosensory system. Here, we used ultra-high-field
      functional magnetic resonance imaging (fMRI) at 7 Tesla to investigate the
      neuronal correlates of tactile motion and pattern processing in humans under
      tightly controlled stimulation conditions. Different types of dynamic stimuli
      created the sensation of moving or stationary bar patterns during passive touch.
      Activity in somatosensory cortex was increased during both motion and pattern
      processing and modulated by motion directionality in primary and secondary
      somatosensory cortices (SI and SII) as well as by pattern orientation in the
      anterior intraparietal sulcus. Furthermore, tactile motion and pattern processing
      induced activity in the middle temporal cortex (hMT+/V5) and in the inferior
      parietal cortex (IPC), involving parts of the supramarginal und angular gyri.
      These responses covaried with subjects' individual perceptual performance,
      suggesting that hMT+/V5 and IPC contribute to conscious perception of specific
      tactile stimulus features. In addition, an analysis of effective connectivity
      using psychophysiological interactions (PPI) revealed increased functional
      coupling between SI and hMT+/V5 during motion processing, as well as between SI
      and IPC during pattern processing. This connectivity pattern provides evidence
      for the direct engagement of these specialized cortical areas in tactile
      processing during somesthesis.

PMID- 21949770
TI  - Comparative SNP and haplotype analysis reveals a higher genetic diversity and
      rapider LD decay in tropical than temperate germplasm in maize.
AB  - Understanding of genetic diversity and linkage disequilibrium (LD) decay in
      diverse maize germplasm is fundamentally important for maize improvement. A total
      of 287 tropical and 160 temperate inbred lines were genotyped with 1943 single
      nucleotide polymorphism (SNP) markers of high quality and compared for genetic
      diversity and LD decay using the SNPs and their haplotypes developed from genic
      and intergenic regions. Intronic SNPs revealed a substantial higher variation
      than exonic SNPs. The big window size haplotypes (3-SNP slide-window covering
      2160 kb on average) revealed much higher genetic diversity than the 10 kb-window
      and gene-window haplotypes. The polymorphic information content values revealed
      by the haplotypes (0.436-0.566) were generally much higher than individual SNPs
      (0.247-0.259). Cluster analysis classified the 447 maize lines into two major
      groups, corresponding to temperate and tropical types. The level of genetic
      diversity and subpopulation structure were associated with the germplasm origin
      and post-domestication selection. Compared to temperate lines, the tropical lines
      had a much higher level of genetic diversity with no significant subpopulation
      structure identified. Significant variation in LD decay distance (2-100 kb) was
      found across the genome, chromosomal regions and germplasm groups. The average of
      LD decay distance (10-100 kb) in the temperate germplasm was two to ten times
      larger than that in the tropical germplasm (5-10 kb). In conclusion, tropical
      maize not only host high genetic diversity that can be exploited for future plant
      breeding, but also show rapid LD decay that provides more opportunity for
      selection.

PMID- 21949771
TI  - Interspecific proteomic comparisons reveal ash phloem genes potentially involved
      in constitutive resistance to the emerald ash borer.
AB  - The emerald ash borer (Agrilus planipennis) is an invasive wood-boring beetle
      that has killed millions of ash trees since its accidental introduction to North
      America. All North American ash species (Fraxinus spp.) that emerald ash borer
      has encountered so far are susceptible, while an Asian species, Manchurian ash
      (F. mandshurica), which shares an evolutionary history with emerald ash borer, is
      resistant. Phylogenetic evidence places North American black ash (F. nigra) and
      Manchurian ash in the same clade and section, yet black ash is highly susceptible
      to the emerald ash borer. This contrast provides an opportunity to compare the
      genetic traits of the two species and identify those with a potential role in
      defense/resistance. We used Difference Gel Electrophoresis (DIGE) to compare the
      phloem proteomes of resistant Manchurian to susceptible black, green, and white
      ash. Differentially expressed proteins associated with the resistant Manchurian
      ash when compared to the susceptible ash species were identified using nano-LC
      MS/MS and putative identities assigned. Proteomic differences were strongly
      associated with the phylogenetic relationships among the four species. Proteins
      identified in Manchurian ash potentially associated with its resistance to
      emerald ash borer include a PR-10 protein, an aspartic protease, a phenylcoumaran
      benzylic ether reductase (PCBER), and a thylakoid-bound ascorbate peroxidase.
      Discovery of resistance-related proteins in Asian species will inform approaches
      in which resistance genes can be introgressed into North American ash species.
      The generation of resistant North American ash genotypes can be used in forest
      ecosystem restoration and urban plantings following the wake of the emerald ash
      borer invasion.

PMID- 21949772
TI  - Molecular population genetics of elicitor-induced resistance genes in European
      aspen (Populus tremula L., Salicaceae).
AB  - Owing to their long life span and ecological dominance in many communities,
      forest trees are subject to attack from a diverse array of herbivores throughout
      their range, and have therefore developed a large number of both constitutive and
      inducible defenses. We used molecular population genetics methods to examine the
      evolution of eight genes in European aspen, Populus tremula, that are all
      associated with defensive responses against pests and/or pathogens, and have
      earlier been shown to become strongly up-regulated in poplars as a response to
      wounding and insect herbivory. Our results show that the majority of these
      defense genes show patterns of intraspecific polymorphism and site-frequency
      spectra that are consistent with a neutral model of evolution. However, two of
      the genes, both belonging to a small gene family of polyphenol oxidases, show
      multiple deviations from the neutral model. The gene PPO1 has a 600 bp region
      with a highly elevated K(A)/K(S) ratio and reduced synonymous diversity. PPO1
      also shows a skew toward intermediate frequency variants in the SFS, and a
      pronounced fixation of non-synonymous mutations, all pointing to the fact that
      PPO1 has been subjected to recurrent selective sweeps. The gene PPO2 shows a
      marked excess of high frequency, derived variants and shows many of the same
      trends as PPO1 does, even though the pattern is less pronounced, suggesting that
      PPO2 might have been the target of a recent selective sweep. Our results supports
      data from both Populus and other species which have found that the the majority
      of defense-associated genes show few signs of selection but that a number of
      genes involved in mediating defense against herbivores show signs of adaptive
      evolution.

PMID- 21949773
TI  - Luminal-applied flagellin is internalized by polarized intestinal epithelial
      cells and elicits immune responses via the TLR5 dependent mechanism.
AB  - Bacteria release flagellin that elicits innate responses via Toll-like receptor 5
      (TLR5). Here, we investigated the fate of apically administrated full length
      flagellin from virulent and avirulent bacteria, along with truncated recombinant
      flagellin proteins in intestinal epithelial cells and cellular responses.
      Flagellin was internalized by intestinal epithelial cell (IEC) monolayers of IEC
      18. Additionally, apically applied flagellin was internalized by polarized human
      Caco-2BBe and T-84 cells in a TLR5 dependent mechanism. More, flagellin exposure
      did not affect the integrity of intestinal monolayers. With immunofluorescent
      staining, internalized flagellin was detected in both early endosomes as well as
      lysosomes. We found that apical exposure of polarized Caco-2BBe and T-84 to
      flagellin from purified Salmonella, Escherichia coli O83:H1 (isolate from Crohn's
      lesion) or avirulent E. coli K12 induced comparable levels of basolateral IL-8
      secretion. A recombinant protein representing the conserved amino (N) and
      carboxyl (C) domains (D) of the flagellin protein (ND1/2ECHCD2/1) induced IL-8
      secretion from IEC similar to levels elicited by full-length flagellins. However,
      a recombinant flagellin protein containing only the D3 hypervariable region
      elicited no IL-8 secretion in both cell lines compared to un-stimulated controls.
      Silencing or blocking TLR5 in Caco-2BBe cells resulted in a lack of flagellin
      internalization and decreased IL-8 secretion. Furthermore, apical exposure to
      flagellin stimulated transepithelial migration of neutrophils and dendritic
      cells. The novel findings in this study show that luminal-applied flagellin is
      internalized by normal IEC via TLR5 and co-localizes to endosomal and lysosomal
      compartments where it is likely degraded as flagellin was not detected on the
      basolateral side of IEC cultures.

PMID- 21949774
TI  - Simulation-based estimates of effectiveness and cost-effectiveness of smoking
      cessation in patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND: The medico-economic impact of smoking cessation considering a smoking
      patient with chronic obstructive pulmonary disease (COPD) is poorly documented.
      OBJECTIVE: Here, considering a COPD smoking patient, the specific burden of
      continuous smoking was estimated, as well as the effectiveness and the cost
      effectiveness of smoking cessation. METHODS: A multi-state Markov model adopting
      society's perspective was developed. Simulated cohorts of English COPD patients
      who are active smokers (all severity stages combined or patients with the same
      initial severity stage) were compared to identical cohorts of patients who quit
      smoking at cohort initialization. Life expectancy, quality adjusted life-years
      (QALY), disease-related costs, and incremental cost-effectiveness ratio (ICER:
      L/QALY) were estimated, considering smoking cessation programs with various
      possible scenarios of success rates and costs. Sensitivity analyses included the
      variation of model key parameters. PRINCIPAL FINDINGS: At the horizon of a
      smoking COPD patient's remaining lifetime, smoking cessation at cohort
      intitialization, relapses being allowed as observed in practice, would result in
      gains (mean) of 1.27 life-years and 0.68 QALY, and induce savings of -1824
      L/patient in the disease-related costs. The corresponding ICER was -2686 L/QALY.
      Smoking cessation resulted in 0.72, 0.69, 0.64 and 0.42 QALY respectively gained
      per mild, moderate, severe, and very severe COPD patient, but was nevertheless
      cost-effective for mild to severe COPD patients in most scenarios, even when
      hypothesizing expensive smoking cessation intervention programmes associated with
      low success rates. Considering a ten-year time horizon, the burden of continuous
      smoking in English COPD patients was estimated to cost a total of 1657 ML while
      452516 QALY would be simultaneously lost. CONCLUSIONS: The study results are a
      useful support for the setting of smoking cessation programmes specifically
      targeted to COPD patients.

PMID- 21949775
TI  - Genomewide analysis of inherited variation associated with phosphorylation of
      PI3K/AKT/mTOR signaling proteins.
AB  - While there exists a wealth of information about genetic influences on gene
      expression, less is known about how inherited variation influences the expression
      and post-translational modifications of proteins, especially those involved in
      intracellular signaling. The PI3K/AKT/mTOR signaling pathway contains several
      such proteins that have been implicated in a number of diseases, including a
      variety of cancers and some psychiatric disorders. To assess whether the
      activation of this pathway is influenced by genetic factors, we measured
      phosphorylated and total levels of three key proteins in the pathway (AKT1,
      p70S6K, 4E-BP1) by ELISA in 122 lymphoblastoid cell lines from 14 families.
      Interestingly, the phenotypes with the highest proportion of genetic influence
      were the ratios of phosphorylated to total protein for two of the pathway
      members: AKT1 and p70S6K. Genomewide linkage analysis suggested several loci of
      interest for these phenotypes, including a linkage peak for the AKT1 phenotype
      that contained the AKT1 gene on chromosome 14. Linkage peaks for the
      phosphorylated:total protein ratios of AKT1 and p70S6K also overlapped on
      chromosome 3. We selected and genotyped candidate genes from under the linkage
      peaks, and several statistically significant associations were found. One
      polymorphism in HSP90AA1 was associated with the ratio of phosphorylated to total
      AKT1, and polymorphisms in RAF1 and GRM7 were associated with the ratio of
      phosphorylated to total p70S6K. These findings, representing the first genomewide
      search for variants influencing human protein phosphorylation, provide useful
      information about the PI3K/AKT/mTOR pathway and serve as a valuable proof of
      concept for studies integrating human genomics and proteomics.

PMID- 21949776
TI  - Biological consequences of ancient gene acquisition and duplication in the large
      genome of Candidatus Solibacter usitatus Ellin6076.
AB  - Members of the bacterial phylum Acidobacteria are widespread in soils and
      sediments worldwide, and are abundant in many soils. Acidobacteria are
      challenging to culture in vitro, and many basic features of their biology and
      functional roles in the soil have not been determined. Candidatus Solibacter
      usitatus strain Ellin6076 has a 9.9 Mb genome that is approximately 2-5 times as
      large as the other sequenced Acidobacteria genomes. Bacterial genome sizes
      typically range from 0.5 to 10 Mb and are influenced by gene duplication,
      horizontal gene transfer, gene loss and other evolutionary processes. Our
      comparative genome analyses indicate that the Ellin6076 large genome has arisen
      by horizontal gene transfer via ancient bacteriophage and/or plasmid-mediated
      transduction, and widespread small-scale gene duplications, resulting in an
      increased number of paralogs. Low amino acid sequence identities among functional
      group members, and lack of conserved gene order and orientation in regions
      containing similar groups of paralogs, suggest that most of the paralogs are not
      the result of recent duplication events. The genome sizes of additional cultured
      Acidobacteria strains were estimated using pulsed-field gel electrophoresis to
      determine the prevalence of the large genome trait within the phylum. Members of
      subdivision 3 had larger genomes than those of subdivision 1, but none were as
      large as the Ellin6076 genome. The large genome of Ellin6076 may not be typical
      of the phylum, and encodes traits that could provide a selective metabolic,
      defensive and regulatory advantage in the soil environment.

PMID- 21949777
TI  - Quasispecies spatial models for RNA viruses with different replication modes and
      infection strategies.
AB  - Empirical observations and theoretical studies suggest that viruses may use
      different replication strategies to amplify their genomes, which impact the
      dynamics of mutation accumulation in viral populations and therefore, their
      fitness and virulence. Similarly, during natural infections, viruses replicate
      and infect cells that are rarely in suspension but spatially organized.
      Surprisingly, most quasispecies models of virus replication have ignored these
      two phenomena. In order to study these two viral characteristics, we have
      developed stochastic cellular automata models that simulate two different modes
      of replication (geometric vs stamping machine) for quasispecies replicating and
      spreading on a two-dimensional space. Furthermore, we explored these two
      replication models considering epistatic fitness landscapes (antagonistic vs
      synergistic) and different scenarios for cell-to-cell spread, one with free
      superinfection and another with superinfection inhibition. We found that the
      master sequences for populations replicating geometrically and with antagonistic
      fitness effects vanished at low critical mutation rates. By contrast, the highest
      critical mutation rate was observed for populations replicating geometrically but
      with a synergistic fitness landscape. Our simulations also showed that for
      stamping machine replication and antagonistic epistasis, a combination that
      appears to be common among plant viruses, populations further increased their
      robustness by inhibiting superinfection. We have also shown that the mode of
      replication strongly influenced the linkage between viral loci, which rapidly
      reached linkage equilibrium at increasing mutations for geometric replication. We
      also found that the strategy that minimized the time required to spread over the
      whole space was the stamping machine with antagonistic epistasis among mutations.
      Finally, our simulations revealed that the multiplicity of infection fluctuated
      but generically increased along time.

PMID- 21949778
TI  - Alien plants introduced by different pathways differ in invasion success:
      unintentional introductions as a threat to natural areas.
AB  - BACKGROUND: Understanding the dimensions of pathways of introduction of alien
      plants is important for regulating species invasions, but how particular pathways
      differ in terms of post-invasion success of species they deliver has never been
      rigorously tested. We asked whether invasion status, distribution and habitat
      range of 1,007 alien plant species introduced after 1500 A.D. to the Czech
      Republic differ among four basic pathways of introduction recognized for plants.
      PRINCIPAL FINDINGS: Pathways introducing alien species deliberately as
      commodities (direct release into the wild; escape from cultivation) result in
      easier naturalization and invasion than pathways of unintentional introduction
      (contaminant of a commodity; stowaway arriving without association with it). The
      proportion of naturalized and invasive species among all introductions delivered
      by a particular pathway decreases with a decreasing level of direct assistance
      from humans associated with that pathway, from release and escape to contaminant
      and stowaway. However, those species that are introduced via unintentional
      pathways and become invasive are as widely distributed as deliberately introduced
      species, and those introduced as contaminants invade an even wider range of
      seminatural habitats. CONCLUSIONS: Pathways associated with deliberate species
      introductions with commodities and pathways whereby species are unintentionally
      introduced are contrasting modes of introductions in terms of invasion success.
      However, various measures of the outcome of the invasion process, in terms of
      species' invasion success, need to be considered to accurately evaluate the role
      of and threat imposed by individual pathways. By employing various measures we
      show that invasions by unintentionally introduced plant species need to be
      considered by management as seriously as those introduced by horticulture,
      because they invade a wide range of seminatural habitats, hence representing even
      a greater threat to natural areas.

PMID- 21949779
TI  - Pharmacological analysis of the activation and receptor properties of the tonic
      GABA(C)R current in retinal bipolar cell terminals.
AB  - GABAergic inhibition in the central nervous system (CNS) can occur via rapid,
      transient postsynaptic currents and via a tonic increase in membrane conductance,
      mediated by synaptic and extrasynaptic GABA(A) receptors (GABA(A)Rs)
      respectively. Retinal bipolar cells (BCs) exhibit a tonic current mediated by
      GABA(C)Rs in their axon terminal, in addition to synaptic GABA(A)R and GABA(C)R
      currents, which strongly regulate BC output. The tonic GABA(C)R current in BC
      terminals (BCTs) is not dependent on vesicular GABA release, but properties such
      as the alternative source of GABA and the identity of the GABA(C)Rs remain
      unknown. Following a recent report that tonic GABA release from cerebellar glial
      cells is mediated by Bestrophin 1 anion channels, we have investigated their role
      in non-vesicular GABA release in the retina. Using patch-clamp recordings from
      BCTs in goldfish retinal slices, we find that the tonic GABA(C)R current is not
      reduced by the anion channel inhibitors NPPB or flufenamic acid but is reduced by
      DIDS, which decreases the tonic current without directly affecting GABA(C)Rs. All
      three drugs also exhibit non-specific effects including inhibition of GABA
      transporters. GABA(C)R rho subunits can form homomeric and heteromeric receptors
      that differ in their properties, but BC GABA(C)Rs are thought to be rho1-rho2
      heteromers. To investigate whether GABA(C)Rs mediating tonic and synaptic
      currents may differ in their subunit composition, as is the case for GABA(A)Rs,
      we have examined the effects of two antagonists that show partial rho subunit
      selectivity: picrotoxin and cyclothiazide. Tonic and synaptic GABA(C)R currents
      were differentially affected by both drugs, suggesting that a population of
      homomeric rho1 receptors contributes to the tonic current. These results extend
      our understanding of the multiple forms of GABAergic inhibition that exist in the
      CNS and contribute to visual signal processing in the retina.

PMID- 21949780
TI  - Reconsidering the sporulation characteristics of hypervirulent Clostridium
      difficile BI/NAP1/027.
AB  - Clostridium difficile is the leading cause of antibiotic-associated diarrhoea and
      a major burden to healthcare services worldwide. In recent years, C. difficile
      strains belonging to the BI/NAP1/027 type have become highly represented among
      clinical isolates. These so-called 'hypervirulent' strains are associated with
      outbreaks of increased disease severity, higher relapse rates and an expanded
      repertoire of antibiotic resistance. Spores, formed during sporulation, play a
      pivotal role in disease transmission and it has been suggested that BI/NAP1/027
      strains are more prolific in terms of sporulation in vitro than 'non-epidemic' C.
      difficile types. Work in our laboratory has since provided credible evidence to
      the contrary suggesting that the strain-to-strain variation in C. difficile
      sporulation characteristics is not type-associated. However, the BI/NAP1/027 type
      is still widely stated to have an increased rate of sporulation. In this study,
      we analysed the sporulation rates of 53 C. difficile strains, the largest sample
      size used to-date in such a study, including 28 BI/NAP1/027 isolates. Our data
      confirm that significant variation exists in the rate at which different C.
      difficile strains form spores. However, we clearly show that the sporulation rate
      of the BI/NAP1/027 type was no higher than that of non-BI/NAP1/027 strains. In
      addition, we observed substantial variation in sporulation characteristics within
      the BI/NAP1/027 type. This work highlights the danger of assuming that all
      strains of one type behave similarly without studying adequate sample sizes.
      Furthermore, we stress the need for more rigorous experimental procedures in
      order to quantify C. difficile sporulation more accurately in the future.

PMID- 21949781
TI  - Circulating fibroblast growth factor 21 levels are closely associated with
      hepatic fat content: a cross-sectional study.
AB  - BACKGROUND AND AIMS: Fibroblasts growth factor 21 (FGF21), a liver-secreted
      endocrine factor involved in regulating glucose and lipid metabolism, has been
      shown to be elevated in patients with non-alcoholic fatty liver disease (NAFLD).
      This study aimed to evaluate the quantitative correlation between serum FGF21
      level and hepatic fat content. METHODS: A total of 138 subjects (72 male and 66
      female) aged from 18 to 65 years with abnormal glucose metabolism and B
      ultrasonography diagnosed fatty liver were enrolled in the study. Serum FGF21
      levels were determined by an in-house chemiluminescence immunoassay and hepatic
      fat contents were measured by proton magnetic resonance spectroscopy. RESULTS:
      Serum FGF21 increased progressively with the increase of hepatic fat content, but
      when hepatic fat content increased to the fourth quartile, FGF21 tended to
      decline. Serum FGF21 concentrations were positively correlated with hepatic fat
      content especially in subjects with mild/moderate hepatic steatosis (r = 0.276, p
      = 0.009). Within the range of hepatic steatosis from the first to third quartile,
      FGF21 was superior to any other traditional clinical markers including ALT to
      reflect hepatic fat content. When the patients with severe hepatic steatosis (the
      fourth quartile) were included, the quantitative correlation between FGF21 and
      hepatic fat content was weakened. CONCLUSIONS: Serum FGF21 was a potential
      biomarker to reflect the hepatic fat content in patients with mild or moderate
      NAFLD. In severe NAFLD patients, FGF21 concentration might decrease due to liver
      inflammation or injury.

PMID- 21949782
TI  - The role of regulated mRNA stability in establishing bicoid morphogen gradient in
      Drosophila embryonic development.
AB  - The Bicoid morphogen is amongst the earliest triggers of differential spatial
      pattern of gene expression and subsequent cell fate determination in the
      embryonic development of Drosophila. This maternally deposited morphogen is
      thought to diffuse in the embryo, establishing a concentration gradient which is
      sensed by downstream genes. In most model based analyses of this process, the
      translation of the bicoid mRNA is thought to take place at a fixed rate from the
      anterior pole of the embryo and a supply of the resulting protein at a constant
      rate is assumed. Is this process of morphogen generation a passive one as assumed
      in the modelling literature so far, or would available data support an alternate
      hypothesis that the stability of the mRNA is regulated by active processes? We
      introduce a model in which the stability of the maternal mRNA is regulated by
      being held constant for a length of time, followed by rapid degradation. With
      this more realistic model of the source, we have analysed three computational
      models of spatial morphogen propagation along the anterior-posterior axis: (a)
      passive diffusion modelled as a deterministic differential equation, (b)
      diffusion enhanced by a cytoplasmic flow term; and (c) diffusion modelled by
      stochastic simulation of the corresponding chemical reactions. Parameter
      estimation on these models by matching to publicly available data on spatio
      temporal Bicoid profiles suggests strong support for regulated stability over
      either a constant supply rate or one where the maternal mRNA is permitted to
      degrade in a passive manner.

PMID- 21949783
TI  - Assessing the effects of symmetry on motif discovery and modeling.
AB  - BACKGROUND: Identifying the DNA binding sites for transcription factors is a key
      task in modeling the gene regulatory network of a cell. Predicting DNA binding
      sites computationally suffers from high false positives and false negatives due
      to various contributing factors, including the inaccurate models for
      transcription factor specificity. One source of inaccuracy in the specificity
      models is the assumption of asymmetry for symmetric models. METHODOLOGY/PRINCIPAL
      FINDINGS: Using simulation studies, so that the correct binding site model is
      known and various parameters of the process can be systematically controlled, we
      test different motif finding algorithms on both symmetric and asymmetric binding
      site data. We show that if the true binding site is asymmetric the results are
      unambiguous and the asymmetric model is clearly superior to the symmetric model.
      But if the true binding specificity is symmetric commonly used methods can infer,
      incorrectly, that the motif is asymmetric. The resulting inaccurate motifs lead
      to lower sensitivity and specificity than would the correct, symmetric models. We
      also show how the correct model can be obtained by the use of appropriate
      measures of statistical significance. CONCLUSIONS/SIGNIFICANCE: This study
      demonstrates that the most commonly used motif-finding approaches usually model
      symmetric motifs incorrectly, which leads to higher than necessary false
      prediction errors. It also demonstrates how alternative motif-finding methods can
      correct the problem, providing more accurate motif models and reducing the
      errors. Furthermore, it provides criteria for determining whether a symmetric or
      asymmetric model is the most appropriate for any experimental dataset.

PMID- 21949784
TI  - Emulsion PCR: a high efficient way of PCR amplification of random DNA libraries
      in aptamer selection.
AB  - Aptamers are short RNA or DNA oligonucleotides which can bind with different
      targets. Typically, they are selected from a large number of random DNA sequence
      libraries. The main strategy to obtain aptamers is systematic evolution of
      ligands by exponential enrichment (SELEX). Low efficiency is one of the
      limitations for conventional PCR amplification of random DNA sequence library in
      aptamer selection because of relative low products and high by-products formation
      efficiency. Here, we developed emulsion PCR for aptamer selection. With this
      method, the by-products formation decreased tremendously to an undetectable
      level, while the products formation increased significantly. Our results
      indicated that by-products in conventional PCR amplification were from primer
      product and product-product hybridization. In emulsion PCR, we can completely
      avoid the product-product hybridization and avoid the most of primer-product
      hybridization if the conditions were optimized. In addition, it also showed that
      the molecule ratio of template to compartment was crucial to by-product formation
      efficiency in emulsion PCR amplification. Furthermore, the concentration of the
      Taq DNA polymerase in the emulsion PCR mixture had a significant impact on
      product formation efficiency. So, the results of our study indicated that
      emulsion PCR could improve the efficiency of SELEX.

PMID- 21949785
TI  - IgE recognition patterns of profilin, PR-10, and tropomyosin panallergens tested
      in 3,113 allergic patients by allergen microarray-based technology.
AB  - BACKGROUND: IgE recognition of panallergens having highly conserved sequence
      regions, structure, and function and shared by inhalant and food allergen sources
      is often observed. METHODS: We evaluated the IgE recognition profile of profilins
      (Bet v 2, Cyn d 12, Hel a 2, Hev b 8, Mer a 1, Ole e 2, Par j 3, Phl p 12, Pho d
      2), PR-10 proteins (Aln g 1, Api g 1, Bet v 1.0101, Bet v 1.0401, Cor a 1, Dau c
      1 and Mal d 1.0108) and tropomyosins (Ani s 3, Der p 10, Hel as 1, Pen i 1, Pen m
      1, Per a 7) using the Immuno-Solid phase Allergen Chip (ISAC) microarray system.
      The three panallergen groups were well represented among the allergenic molecules
      immobilized on the ISAC. Moreover, they are distributed in several taxonomical
      allergenic sources, either close or distant, and have a route of exposure being
      either inhalation or ingestion. RESULTS: 3,113 individuals (49.9% female) were
      selected on the basis of their reactivity to profilins, PR-10 or tropomyosins.
      1,521 (48.8%) patients were reactive to profilins (77.6% Mer a 1 IgE(+)), 1,420
      (45.6%) to PR-10 (92.5% Bet v 1 IgE(+)) and 632 (20.3%) to tropomyosins (68% Der
      p 10 IgE(+)). A significant direct relationship between different representative
      molecules within each group of panallergens was found. 2,688 patients (86.4%)
      recognized only one out of the three distinct groups of molecules as confirmed
      also by hierarchical clustering analysis. CONCLUSIONS: Unless exposed to most of
      the allergens in the same or related allergenic sources, a preferential IgE
      response to distinct panallergens has been recorded. Allergen microarray IgE
      testing increases our knowledge of the IgE immune response and related
      epidemiological features within and between homologous molecules better
      describing the patients' immunological phenotypes.

PMID- 21949786
TI  - Quantitative phosphoproteomics of CXCL12 (SDF-1) signaling.
AB  - CXCL12 (SDF-1) is a chemokine that binds to and signals through the seven
      transmembrane receptor CXCR4. The CXCL12/CXCR4 signaling axis has been implicated
      in both cancer metastases and human immunodeficiency virus type 1 (HIV-1)
      infection and a more complete understanding of CXCL12/CXCR4 signaling pathways
      may support efforts to develop therapeutics for these diseases. Mass spectrometry
      based phosphoproteomics has emerged as an important tool in studying signaling
      networks in an unbiased fashion. We employed stable isotope labeling with amino
      acids in cell culture (SILAC) quantitative phosphoproteomics to examine the
      CXCL12/CXCR4 signaling axis in the human lymphoblastic CEM cell line. We
      quantified 4,074 unique SILAC pairs from 1,673 proteins and 89 phosphopeptides
      were deemed CXCL12-responsive in biological replicates. Several well established
      CXCL12-responsive phosphosites such as AKT (pS473) and ERK2 (pY204) were
      confirmed in our study. We also validated two novel CXCL12-responsive
      phosphosites, stathmin (pS16) and AKT1S1 (pT246) by Western blot. Pathway
      analysis and comparisons with other phosphoproteomic datasets revealed that genes
      from CXCL12-responsive phosphosites are enriched for cellular pathways such as T
      cell activation, epidermal growth factor and mammalian target of rapamycin (mTOR)
      signaling, pathways which have previously been linked to CXCL12/CXCR4 signaling.
      Several of the novel CXCL12-responsive phosphoproteins from our study have also
      been implicated with cellular migration and HIV-1 infection, thus providing an
      attractive list of potential targets for the development of cancer metastasis and
      HIV-1 therapeutics and for furthering our understanding of chemokine signaling
      regulation by reversible phosphorylation.

PMID- 21949787
TI  - Angiomyolipoma have common mutations in TSC2 but no other common genetic events.
AB  - Renal angiomyolipoma are part of the PEComa family of neoplasms, and occur both
      in association with Tuberous Sclerosis Complex (TSC) and independent of that
      disorder. Previous studies on the molecular genetic alterations that occur in
      angiomyolipoma are very limited. We evaluated 9 angiomyolipoma for which frozen
      tissue was available from a consecutive surgical series. Seven of 8 samples
      subjected to RT-PCR-cDNA sequencing showed mutations in TSC2; none showed
      mutations in TSC1 or RHEB. Six of the seven mutations were deletions. We searched
      for 983 activating and inactivating mutations in 115 genes, and found none in
      these tumors. Similarly analysis for genomic regions of loss or gain, assessed by
      Affymetrix SNP6.0 analysis, showed no abnormalities. Loss of heterozygosity in
      the TSC2 region was commonly seen, except in patients with low frequency TSC2
      mutations. We conclude that sporadic renal angiomyolipoma usually have mutations
      in TSC2, but not TSC1 or RHEB, and have no other common genomic events, among
      those we searched for. However, chromosomal translocations and gene fusion events
      were not assessed here. TSC2 inactivation by mutation is a consistent and likely
      necessary genetic event in the pathogenesis of most angiomyolipoma.

PMID- 21949788
TI  - Epigenetic regulation of microRNA genes and the role of miR-34b in cell invasion
      and motility in human melanoma.
AB  - Invasive melanoma is the most lethal form of skin cancer. The treatment of
      melanoma-derived cell lines with 5-aza-2'-deoxycytidine (5-Aza-dC) markedly
      increases the expression of several miRNAs, suggesting that the miRNA-encoding
      genes might be epigenetically regulated, either directly or indirectly, by DNA
      methylation. We have identified a group of epigenetically regulated miRNA genes
      in melanoma cells, and have confirmed that the upstream CpG island sequences of
      several such miRNA genes are hypermethylated in cell lines derived from different
      stages of melanoma, but not in melanocytes and keratinocytes. We used direct DNA
      bisulfite and immunoprecipitated DNA (Methyl-DIP) to identify changes in CpG
      island methylation in distinct melanoma patient samples classified as primary in
      situ, regional metastatic, and distant metastatic. Two melanoma cell lines
      (WM1552C and A375 derived from stage 3 and stage 4 human melanoma, respectively)
      were engineered to ectopically express one of the epigenetically modified miRNA:
      miR-34b. Expression of miR-34b reduced cell invasion and motility rates of both
      WM1552C and A375, suggesting that the enhanced cell invasiveness and motility
      observed in metastatic melanoma cells may be related to their reduced expression
      of miR-34b. Total RNA isolated from control or miR-34b-expressing WM1552C cells
      was subjected to deep sequencing to identify gene networks around miR-34b. We
      identified network modules that are potentially regulated by miR-34b, and which
      suggest a mechanism for the role of miR-34b in regulating normal cell motility
      and cytokinesis.

PMID- 21949789
TI  - Exposed hydrophobic residues in human immunodeficiency virus type 1 Vpr helix-1
      are important for cell cycle arrest and cell death.
AB  - The human immunodeficiency virus type 1 (HIV-1) accessory protein viral protein R
      (Vpr) is a major determinant for virus-induced G2/M cell cycle arrest and
      cytopathicity. Vpr is thought to perform these functions through the interaction
      with partner proteins. The NMR structure of Vpr revealed solvent exposed
      hydrophobic amino acids along helices 1 and 3 of Vpr, which could be putative
      protein binding domains. We previously showed that the hydrophobic patch along
      helix-3 was important for G2/M blockade and cytopathicity. Mutations of the
      exposed hydrophobic residues along helix-1 were found to reduce Vpr-induced cell
      cycle arrest and cell death as well. The levels of toxicity during virion
      delivery of Vpr correlated with G2/M arrest. Thus, the exposed hydrophobic amino
      acids in the amino-terminal helix-1 are important for the cell cycle arrest and
      cytopathicity functions of Vpr.

PMID- 21949790
TI  - Human NK cells differ more in their KIR2DL1-dependent thresholds for HLA-Cw6
      mediated inhibition than in their maximal killing capacity.
AB  - In this study we have addressed the question of how activation and inhibition of
      human NK cells is regulated by the expression level of MHC class I protein on
      target cells. Using target cell transfectants sorted to stably express different
      levels of the MHC class I protein HLA-Cw6, we show that induction of
      degranulation and that of IFN-gamma secretion are not correlated. In contrast,
      the inhibition of these two processes by MHC class-I occurs at the same level of
      class I MHC protein. Primary human NK cell clones were found to differ in the
      amount of target MHC class I protein required for their inhibition, rather than
      in their maximum killing capacity. Importantly, we show that KIR2DL1 expression
      determines the thresholds (in terms of MHC I protein levels) required for NK cell
      inhibition, while the expression of other receptors such as LIR1 is less
      important. Furthermore, using mathematical models to explore the dynamics of
      target cell killing, we found that the observed delay in target cell killing is
      exhibited by a model in which NK cells require some activation or priming, such
      that each cell can lyse a target cell only after being activated by a first
      encounter with the same or a different target cell, but not by models which lack
      this feature.

PMID- 21949791
TI  - Serotonin augments gut pacemaker activity via 5-HT3 receptors.
AB  - Serotonin (5-hydroxytryptamine: 5-HT) affects numerous functions in the gut, such
      as secretion, muscle contraction, and enteric nervous activity, and therefore to
      clarify details of 5-HT's actions leads to good therapeutic strategies for gut
      functional disorders. The role of interstitial cells of Cajal (ICC), as pacemaker
      cells, has been recognised relatively recently. We thus investigated 5-HT actions
      on ICC pacemaker activity. Muscle preparations with myenteric plexus were
      isolated from the murine ileum. Spatio-temporal measurements of intracellular
      Ca(2+) and electric activities in ICC were performed by employing fluorescent
      Ca(2+) imaging and microelectrode array (MEA) systems, respectively.
      Dihydropyridine (DHP) Ca(2+) antagonists and tetrodotoxin (TTX) were applied to
      suppress smooth muscle and nerve activities, respectively. 5-HT significantly
      enhanced spontaneous Ca(2+) oscillations that are considered to underlie electric
      pacemaker activity in ICC. LY-278584, a 5-HT(3) receptor antagonist suppressed
      spontaneous Ca(2+) activity in ICC, while 2-methylserotonin (2-Me-5-HT), a 5
      HT(3) receptor agonist, restored it. GR113808, a selective antagonist for 5
      HT(4), and O-methyl-5-HT (O-Me-5-HT), a non-selective 5-HT receptor agonist
      lacking affinity for 5-HT(3) receptors, had little effect on ICC Ca(2+) activity.
      In MEA measurements of ICC electric activity, 5-HT and 2-Me-5-HT caused
      excitatory effects. RT-PCR and immunostaining confirmed expression of 5-HT(3)
      receptors in ICC. The results indicate that 5-HT augments ICC pacemaker activity
      via 5-HT(3) receptors. ICC appear to be a promising target for treatment of
      functional motility disorders of the gut, for example, irritable bowel syndrome.

PMID- 21949792
TI  - RNA oxidation adducts 8-OHG and 8-OHA change with Abeta42 levels in late-stage
      Alzheimer's disease.
AB  - While research supports amyloid-beta (Abeta) as the etiologic agent of
      Alzheimer's disease (AD), the mechanism of action remains unclear. Evidence
      indicates that adducts of RNA caused by oxidation also represent an early
      phenomenon in AD. It is currently unknown what type of influence these two
      observations have on each other, if any. We quantified five RNA adducts by gas
      chromatography/mass spectroscopy across five brain regions from AD cases and age
      matched controls. We then used a reductive directed analysis to compare the RNA
      adducts to common indices of AD neuropathology and various pools of Abeta. Using
      data from four disease-affected brain regions (Brodmann's Area 9, hippocampus,
      inferior parietal lobule, and the superior and middle temporal gyri), we found
      that the RNA adduct 8-hydroxyguanine (8-OHG) decreased, while 8-hydroxyadenine (8
      OHA) increased in AD. The cerebellum, which is generally spared in AD, did not
      show disease related changes, and no RNA adducts correlated with the number of
      plaques or tangles. Multiple regression analysis revealed that SDS-soluble
      Abeta(42) was the best predictor of changes in 8-OHG, while formic acid-soluble
      Abeta(42) was the best predictor of changes in 8-OHA. This study indicates that
      although there is a connection between AD related neuropathology and RNA
      oxidation, this relationship is not straightforward.

PMID- 21949793
TI  - Evidence implicating the Ras pathway in multiple CD28 costimulatory functions in
      CD4+ T cells.
AB  - CD28 costimulation is a critical event in the full activation of CD4(+) T cells
      that augments cytokine gene transcription, promotes cytokine mRNA stability,
      prevents induction of anergy, increases cellular metabolism, and increases cell
      survival. However, despite extensive biochemical analysis of the signaling events
      downstream of CD28, molecular pathways sufficient to functionally replace the
      diverse aspects of CD28-mediated costimulation in normal T cells have not been
      identified. Ras/MAPK signaling is a critical pathway downstream of T cell
      receptor stimulation, but its role in CD28-mediated costimulation has been
      controversial. We observed that physiologic CD28 costimulation caused a
      relocalization of the RasGEF RasGRP to the T cell-APC interface by confocal
      microscopy. In whole cell biochemical analysis, CD28 cross-linking with either
      anti-CD28 antibody or B7.1-Ig augmented TCR-induced Ras activation. To determine
      whether Ras signaling was sufficient to functionally mimic CD28 costimulation, we
      utilized an adenoviral vector encoding constitutively active H-Ras (61L) to
      transduce normal, Coxsackie-Adenovirus Receptor (CAR) transgenic CD4(+) T cells.
      Like costimulation via CD28, active Ras induced AKT, JNK and ERK phosphorylation.
      In addition, constitutive Ras signaling mimicked the ability of CD28 to
      costimulate IL-2 protein secretion, prevent anergy induction, increase glucose
      uptake, and promote cell survival. Importantly, we also found that active Ras
      mimicked the mechanism by which CD28 costimulates IL-2 production: by increasing
      IL-2 gene transcription, and promoting IL-2 mRNA stability. Finally, active Ras
      was able to induce IL-2 production when combined with ionomycin stimulation in a
      MEK-1-dependent fashion. Our results are consistent with a central role for Ras
      signaling in CD28-mediated costimulation.

PMID- 21949794
TI  - Influence of body position on cortical pain-related somatosensory processing: an
      ERP study.
AB  - BACKGROUND: Despite the consistent information available on the physiological
      changes induced by head down bed rest, a condition which simulates space
      microgravity, our knowledge on the possible perceptual-cortical alterations is
      still poor. The present study investigated the effects of 2-h head-down bed rest
      on subjective and cortical responses elicited by electrical, pain-related
      somatosensory stimulation. METHODOLOGY/PRINCIPAL FINDINGS: Twenty male subjects
      were randomly assigned to two groups, head-down bed rest (BR) or sitting control
      condition. Starting from individual electrical thresholds, Somatosensory Evoked
      Potentials were elicited by electrical stimuli administered randomly to the left
      wrist and divided into four conditions: control painless condition, electrical
      pain threshold, 30% above pain threshold, 30% below pain threshold. Subjective
      pain ratings collected during the EEG session showed significantly reduced pain
      perception in BR compared to Control group. Statistical analysis on four
      electrode clusters and sLORETA source analysis revealed, in sitting controls, a
      P1 component (40-50 ms) in the right somatosensory cortex, whereas it was
      bilateral and differently located in BR group. Controls' N1 (80-90 ms) had
      widespread right hemisphere activation, involving also anterior cingulate,
      whereas BR group showed primary somatosensory cortex activation. The P2 (190-220
      ms) was larger in left-central locations of Controls compared with BR group.
      CONCLUSIONS/SIGNIFICANCE: Head-down bed rest was associated to an overall
      decrease of pain sensitivity and an altered pain network also outside the primary
      somatosensory cortex. Results have implications not only for astronauts' health
      and spaceflight risks, but also for the clinical aspects of pain detection in
      bedridden patients at risk of fatal undetected complications.

PMID- 21949795
TI  - Ontogeny of the alligator cartilago transiliens and its significance for
      sauropsid jaw muscle evolution.
AB  - The cartilago transiliens is a fibrocartilaginous structure within the jaw
      muscles of crocodylians. The cartilago transiliens slides between the pterygoid
      buttress and coronoid region of the lower jaw and connects two muscles
      historically identified as m. pseudotemporalis superficialis and m.
      intramandibularis. However, the position of cartilago transiliens, and its
      anatomical similarities to tendon organs suggest the structure may be a sesamoid
      linking a single muscle. Incompressible sesamoids often form inside tendons that
      wrap around bone. However, such structures rarely ossify in reptiles and have
      thus far received scant attention. We tested the hypothesis that the cartilago
      transiliens is a sesamoid developed within in one muscle by investigating its
      structure in an ontogenetic series of Alligator mississippiensis using
      dissection, 3D imaging, and polarizing and standard light microscopy. In all
      animals studied, the cartilago transiliens receives collagen fibers and tendon
      insertions from its two main muscular attachments. However, whereas collagen
      fibers were continuous within the cartilaginous nodule of younger animals, such
      continuity decreased in older animals, where the fibrocartilaginous core grew to
      displace the fibrous region. Whereas several neighboring muscles attached to the
      fibrous capsule in older individuals, only two muscles had significant
      contributions to the structure in young animals. Our results indicate that the
      cartilago transiliens is likely a sesamoid formed within a single muscle (i.e.,
      m. pseudotemporalis superficialis) as it wraps around the pterygoid buttress.
      This tendon organ is ubiquitous among fossil crocodyliforms indicating it is a
      relatively ancient, conserved structure associated with the development of the
      large pterygoid flanges in this clade. Finally, these findings indicate that
      similar tendon organs exist among potentially homologous muscle groups in birds
      and turtles, thus impacting inferences of jaw muscle homology and evolution in
      sauropsids in general.

PMID- 21949796
TI  - Using combined morphological, allometric and molecular approaches to identify
      species of the genus Raillietiella (Pentastomida).
AB  - Taxonomic studies of parasites can be severely compromised if the host species
      affects parasite morphology; an uncritical analysis might recognize multiple taxa
      simply because of phenotypically plastic responses of parasite morphology to host
      physiology. Pentastomids of the genus Raillietiella are endoparasitic crustaceans
      primarily infecting the respiratory system of carnivorous reptiles, but also
      recorded from bufonid anurans. The delineation of pentastomids at the generic
      level is clear, but the taxonomic status of many species is not. We collected
      raillietiellids from lungs of the invasive cane toad (Rhinella marina), the
      invasive Asian house gecko (Hemidactylus frenatus), and a native tree frog
      (Litoria caerulea) in tropical Australia, and employed a combination of genetic
      analyses, and traditional and novel morphological methods to clarify their
      identity. Conventional analyses of parasite morphology (which focus on raw values
      of morphological traits) revealed two discrete clusters in terms of pentastome
      hook size, implying two different species of pentastomes: one from toads and a
      tree frog (Raillietiella indica) and another from lizards (Raillietiella
      frenatus). However, these clusters disappeared in allometric analyses that took
      pentastome body size into account, suggesting that only a single pentastome taxon
      may be involved. Our molecular data revealed no genetic differences between
      parasites in toads versus lizards, confirming that there was only one species: R.
      frenatus. This pentastome (previously known only from lizards) clearly is also
      capable of maturing in anurans. Our analyses show that the morphological features
      used in pentastomid taxonomy change as the parasite transitions through
      developmental stages in the definitive host. To facilitate valid descriptions of
      new species of pentastomes, future taxonomic work should include both
      morphological measurements (incorporating quantitative measures of body size and
      hook bluntness) and molecular data.

PMID- 21949797
TI  - Tidying up international nucleotide sequence databases: ecological, geographical
      and sequence quality annotation of its sequences of mycorrhizal fungi.
AB  - Sequence analysis of the ribosomal RNA operon, particularly the internal
      transcribed spacer (ITS) region, provides a powerful tool for identification of
      mycorrhizal fungi. The sequence data deposited in the International Nucleotide
      Sequence Databases (INSD) are, however, unfiltered for quality and are often
      poorly annotated with metadata. To detect chimeric and low-quality sequences and
      assign the ectomycorrhizal fungi to phylogenetic lineages, fungal ITS sequences
      were downloaded from INSD, aligned within family-level groups, and examined
      through phylogenetic analyses and BLAST searches. By combining the fungal
      sequence database UNITE and the annotation and search tool PlutoF, we also added
      metadata from the literature to these accessions. Altogether 35,632 sequences
      belonged to mycorrhizal fungi or originated from ericoid and orchid mycorrhizal
      roots. Of these sequences, 677 were considered chimeric and 2,174 of low read
      quality. Information detailing country of collection, geographical coordinates,
      interacting taxon and isolation source were supplemented to cover 78.0%, 33.0%,
      41.7% and 96.4% of the sequences, respectively. These annotated sequences are
      publicly available via UNITE (http://unite.ut.ee/) for downstream biogeographic,
      ecological and taxonomic analyses. In European Nucleotide Archive (ENA;
      http://www.ebi.ac.uk/ena/), the annotated sequences have a special link-out to
      UNITE. We intend to expand the data annotation to additional genes and all
      taxonomic groups and functional guilds of fungi.

PMID- 21949798
TI  - Interpopulation variation in contour feather structure is environmentally
      determined in great tits.
AB  - BACKGROUND: The plumage of birds is important for flying, insulation and social
      communication. Contour feathers cover most of the avian body and among other
      functions they provide a critical insulation layer against heat loss. Feather
      structure and composition are known to vary among individuals, which in turn
      determines variation in the insulation properties of the feather. However, the
      extent and the proximate mechanisms underlying this variation remain unexplored.
      METHODOLOGY/PRINCIPAL FINDINGS: We analyzed contour feather structure from two
      different great tit populations adapted to different winter regimes, one northern
      population in Oulu (Finland) and one southern population in Lund (Sweden). Great
      tits from the two populations differed significantly in feather structure. Birds
      from the northern population had a denser plumage but consisting of shorter
      feathers with a smaller proportion containing plumulaceous barbs, compared with
      conspecifics from the southern population. However, differences disappeared when
      birds originating from the two populations were raised and moulted in identical
      conditions in a common-garden experiment located in Oulu, under ad libitum
      nutritional conditions. All birds raised in the aviaries, including adult foster
      parents moulting in the same captive conditions, developed a similar feather
      structure. These feathers were different from that of wild birds in Oulu but
      similar to wild birds in Lund, the latter moulting in more benign conditions than
      those of Oulu. CONCLUSIONS/SIGNIFICANCE: Wild populations exposed to different
      conditions develop contour feather differences either due to plastic responses or
      constraints. Environmental conditions, such as nutrient availability during
      feather growth play a crucial role in determining such differences in plumage
      structure among populations.

PMID- 21949799
TI  - Predicting the lay preventive strategies in response to avian influenza from
      perceptions of the threat.
AB  - BACKGROUND: The identification of patterns of behaviors that lay people would
      engage in to protect themselves from the risk of infection in the case of avian
      influenza outbreak, as well as the lay perceptions of the threat that underlie
      these risk reduction strategies. METHODOLOGY/PRINCIPAL FINDINGS: A population
      based survey (N = 1003) was conducted in 2008 to understand and describe how the
      French public might respond to a possible outbreak. Factor analyses highlighted
      three main categories of risk reduction strategies consisting of food quality
      assurance, food avoidance, and animal avoidance. In combination with the fear of
      contracting avian influenza, mental representations associated with the
      manifestation and/or transmission of the disease were found to significantly and
      systematically shape the behavioral responses to the perceived threat.
      CONCLUSIONS/SIGNIFICANCE: This survey provides insight into the nature and
      predictors of the protective patterns that might be expected from the general
      public during a novel domestic outbreak of avian influenza.

PMID- 21949800
TI  - Performance of genotype imputation for rare variants identified in exons and
      flanking regions of genes.
AB  - Genotype imputation has the potential to assess human genetic variation at a
      lower cost than assaying the variants using laboratory techniques. The
      performance of imputation for rare variants has not been comprehensively studied.
      We utilized 8865 human samples with high depth resequencing data for the exons
      and flanking regions of 202 genes and Genome-Wide Association Study (GWAS) data
      to characterize the performance of genotype imputation for rare variants. We
      evaluated reference sets ranging from 100 to 3713 subjects for imputing into
      samples typed for the Affymetrix (500K and 6.0) and Illumina 550K GWAS panels.
      The proportion of variants that could be well imputed (true r(2)>0.7) with a
      reference panel of 3713 individuals was: 31% (Illumina 550K) or 25% (Affymetrix
      500K) with MAF (Minor Allele Frequency) less than or equal 0.001, 48% or 35% with
      0.001<MAF< = 0.005, 54% or 38% with 0.005<MAF< = 0.01, 78% or 57% with 0.01<MAF<
      = 0.05, and 97% or 86% with MAF>0.05. The performance for common SNPs (MAF>0.05)
      within exons and flanking regions is comparable to imputation of more uniformly
      distributed SNPs. The performance for rare SNPs (0.01<MAF< = 0.05) was much more
      dependent on the GWAS panel and the number of reference samples. These results
      suggest routine use of genotype imputation for extending the assessment of common
      variants identified in humans via targeted exon resequencing into additional
      samples with GWAS data, but imputation of very rare variants (MAF< = 0.005) will
      require reference panels with thousands of subjects.

PMID- 21949801
TI  - Comparative accuracy of anal and cervical cytology in screening for moderate to
      severe dysplasia by magnification guided punch biopsy: a meta-analysis.
AB  - BACKGROUND: The accuracy of screening for anal cancer precursors relative to
      screening for cervical cancer precursors has not been systematically examined.
      The aim of the current meta-analysis was to compare the relative accuracy of anal
      cytology to cervical cytology in discriminating between histopathologic high
      grade and lesser grades of dysplasia when the reference standard biopsy is
      obtained using colposcope magnification. METHODS AND FINDINGS: The outcome metric
      of discrimination was the receiver operating characteristic (ROC) curve area.
      Random effects meta-analysis of eligible studies was performed with examination
      of sources of heterogeneity that included QUADAS criteria and selected
      covariates, in meta-regression models. Thirty three cervical and eleven anal
      screening studies were found to be eligible. The primary meta-analytic comparison
      suggested that anal cytologic screening is somewhat less discriminating than
      cervical cytologic screening (ROC area [95% confidence interval (C.I.)]: 0.834
      [0.809-0.859] vs. 0.700 [0.664-0.735] for cervical and anal screening,
      respectively). This finding was robust when examined in meta-regression models of
      covariates differentially distributed by screening setting (anal, cervical).
      CONCLUSIONS: Anal cytologic screening is somewhat less discriminating than
      cervical cytologic screening. Heterogeneity of estimates within each screening
      setting suggests that other factors influence estimates of screening accuracy.
      Among these are sampling and interpretation errors involving both cytology and
      biopsy as well as operator skill and experience.

PMID- 21949802
TI  - Identification of a negative allosteric site on human alpha4beta2 and alpha3beta4
      neuronal nicotinic acetylcholine receptors.
AB  - Acetylcholine-based neurotransmission is regulated by cationic, ligand-gated ion
      channels called nicotinic acetylcholine receptors (nAChRs). These receptors have
      been linked to numerous neurological diseases and disorders such as Alzheimer's
      disease, Parkinson's disease, and nicotine addiction. Recently, a class of
      compounds has been discovered that antagonize nAChR function in an allosteric
      fashion. Models of human alpha4beta2 and alpha3beta4 nicotinic acetylcholine
      receptor (nAChR) extracellular domains have been developed to computationally
      explore the binding of these compounds, including the dynamics and free energy
      changes associated with ligand binding. Through a blind docking study to multiple
      receptor conformations, the models were used to determine a putative binding mode
      for the negative allosteric modulators. This mode, in close proximity to the
      agonist binding site, is presented in addition to a hypothetical mode of
      antagonism that involves obstruction of C loop closure. Molecular dynamics
      simulations and MM-PBSA free energy of binding calculations were used as
      computational validation of the predicted binding mode, while functional assays
      on wild-type and mutated receptors provided experimental support. Based on the
      proposed binding mode, two residues on the beta2 subunit were independently
      mutated to the corresponding residues found on the beta4 subunit. The T58K
      mutation resulted in an eight-fold decrease in the potency of KAB-18, a compound
      that exhibits preferential antagonism for human alpha4beta2 over alpha3beta4
      nAChRs, while the F118L mutation resulted in a loss of inhibitory activity for
      KAB-18 at concentrations up to 100 uM. These results demonstrate the selectivity
      of KAB-18 for human alpha4beta2 nAChRs and validate the methods used for
      identifying the nAChR modulator binding site. Exploitation of this site may lead
      to the development of more potent and subtype-selective nAChR antagonists which
      may be used in the treatment of a number of neurological diseases and disorders.

PMID- 21949803
TI  - Long-distance signals are required for morphogenesis of the regenerating Xenopus
      tadpole tail, as shown by femtosecond-laser ablation.
AB  - BACKGROUND: With the goal of learning to induce regeneration in human beings as a
      treatment for tissue loss, research is being conducted into the molecular and
      physiological details of the regeneration process. The tail of Xenopus laevis
      tadpoles has recently emerged as an important model for these studies; we
      explored the role of the spinal cord during tadpole tail regeneration. METHODS
      AND RESULTS: Using ultrafast lasers to ablate cells, and Geometric Morphometrics
      to quantitatively analyze regenerate morphology, we explored the influence of
      different cell populations. For at least twenty-four hours after amputation
      (hpa), laser-induced damage to the dorsal midline affected the morphology of the
      regenerated tail; damage induced 48 hpa or later did not. Targeting different
      positions along the anterior-posterior (AP) axis caused different shape changes
      in the regenerate. Interestingly, damaging two positions affected regenerate
      morphology in a qualitatively different way than did damaging either position
      alone. Quantitative comparison of regenerate shapes provided strong evidence
      against a gradient and for the existence of position-specific morphogenetic
      information along the entire AP axis. CONCLUSIONS: We infer that there is a
      conduit of morphology-influencing information that requires a continuous dorsal
      midline, particularly an undamaged spinal cord. Contrary to expectation, this
      information is not in a gradient and it is not localized to the regeneration bud.
      We present a model of morphogenetic information flow from tissue undamaged by
      amputation and conclude that studies of information coming from far outside the
      amputation plane and regeneration bud will be critical for understanding
      regeneration and for translating fundamental understanding into biomedical
      approaches.

PMID- 21949804
TI  - Contribution of the caspase gene sequence diversification to the specifically
      antiviral defense in invertebrate.
AB  - Vertebrates achieve adaptive immunity of all sorts against pathogens through the
      diversification of antibodies. However the mechanism of invertebrates' innate
      immune defense against various pathogens remains largely unknown. Our study used
      shrimp and white spot syndrome virus (WSSV) to show that PjCaspase, a caspase
      gene of shrimp that is crucial in apoptosis, possessed gene sequence diversity.
      At present, the role of gene sequence diversity in immunity has not been
      characterized. To address this issue, we compared the PjCaspase gene sequence
      diversities from WSSV-free and WSSV-resistant shrimp. The sequence analysis
      indicated that the PjCaspase gene from the WSSV-resistant shrimp contained a
      special fragment, designated as fragment 3 (221-229 aa). Down-regulation or
      overexpression of the PjCaspase gene containing fragment 3 led to significant
      inhibition or enhancement of virus-induced apoptosis, but had no effect on
      bacterium challenge. We found evidence that the silencing or overexpression of
      this gene led to a 7-fold increase or 11-fold decrease of WSSV copies,
      respectively. Our results suggested that the PjCaspase gene containing fragment 3
      provided the molecular basis for the antiviral defense of shrimp. This study
      represented the first report of the role of gene sequence diversity in the
      immunity of an invertebrate against virus infection. Invertebrates may employ
      this gene sequence diversity as a system to avoid pathogen interference with
      their immune response.

PMID- 21949805
TI  - Establishment and characterization of a transgenic mouse model for in vivo
      imaging of Bmp4 expression in the pancreas.
AB  - Type-2 diabetes results from the development of insulin resistance and a
      concomitant impairment of insulin secretion. Bone morphogenetic protein 4 (Bmp4)
      Bmp receptor 1A signaling in beta cells has recently been reported to be required
      for insulin production and secretion. In addition, Bmp4 blocks the
      differentiation and promotes the expansion of endocrine progenitor cells. Bmp4
      therefore regulates the maintenance of homeostasis in the pancreas. In this
      study, we constructed a reporter plasmid carrying 7-kb enhancer and promoter
      region of the Bmp4 gene upstream of the firefly luciferase gene. We used this
      construct to produce transgenic mice by pro-nuclear microinjection, for
      subsequent in vivo monitoring of Bmp4 expression. The bioluminescent signal was
      detected mainly in the pancreas in three independent lines of transgenic mice.
      Furthermore, the bioluminescent signal was enhanced in association with the
      autophagy response to 24-h fasting. These results suggest that pancreatic
      expression of Bmp4 is involved in responding to the physiological environment,
      including through autophagy. These mouse models represent useful tools for
      toxicological screening, and for investigating the mechanisms responsible for
      pancreatic Bmp4 functions in vivo, with relevance to improving our understanding
      of pancreatic diseases.

PMID- 21949806
TI  - Molecular mining of alleles in water buffalo Bubalus bubalis and characterization
      of the TSPY1 and COL6A1 genes.
AB  - BACKGROUND: Minisatellites are an integral part of eukaryotic genomes and show
      variation in the complexity of their organization. Besides their presence in non
      coding regions, a small fraction of them are part of the transcriptome, possibly
      participating in gene regulation, expression and silencing. We studied the
      minisatellite (TGG)(n) tagged transcriptome in the water buffalo Bubalus bubalis
      across various tissues and the spermatozoa, and characterized the genes TSPY1 and
      COL6A1 discovered in the process. RESULTS: Minisatellite associated sequence
      amplification (MASA) conducted using cDNA and oligonucleotide primer (TGG)(5)
      uncovered 38 different mRNA transcripts from somatic tissues and gonads and 15
      from spermatozoa. These mRNA transcripts corresponded to several known and novel
      genes. The majority of the transcripts showed the highest level of expression
      either in the testes or spermatozoa with exception of a few showing higher
      expression levels in the lungs and liver. Transcript SR1, which is expressed in
      all the somatic tissues and gonads, was found to be similar to the Bos taurus
      collagen type VI alpha 1 gene (COL6A1). Similarly, SR29, a testis-specific
      transcript, was found to be similar to the Bos taurus testis-specific Y-encoded
      protein-1 representing cancer/testis antigen 78 (CT78). Subsequently, full length
      coding sequences (cds) of these two transcripts were obtained. Quantitative PCR
      (q-PCR) revealed 182-202 copies of the TSPY1 gene in water buffalo, which
      localized to the Y chromosome. CONCLUSIONS: The MASA approach enabled us to
      identify several genes, including two of clinical significance, without screening
      an entire cDNA library. Genes identified with TGG repeats are not part of a
      specific family of proteins and instead are distributed randomly throughout the
      genome. Genes showing elevated expression in the testes and spermatozoa may prove
      to be potential candidates for in-depth characterization. Furthermore, their
      possible involvement in fertility or lack thereof would augment animal
      biotechnology.

PMID- 21949807
TI  - Discrimination of timbre in early auditory responses of the human brain.
AB  - BACKGROUND: The issue of how differences in timbre are represented in the neural
      response still has not been well addressed, particularly with regard to the
      relevant brain mechanisms. Here we employ phasing and clipping of tones to
      produce auditory stimuli differing to describe the multidimensional nature of
      timbre. We investigated the auditory response and sensory gating as well, using
      by magnetoencephalography (MEG). METHODOLOGY/PRINCIPAL FINDINGS: Thirty-five
      healthy subjects without hearing deficit participated in the experiments. Two
      different or same tones in timbre were presented through conditioning (S1)
      testing (S2) paradigm as a pair with an interval of 500 ms. As a result, the
      magnitudes of auditory M50 and M100 responses were different with timbre in both
      hemispheres. This result might support that timbre, at least by phasing and
      clipping, is discriminated in the auditory early processing. The second response
      in a pair affected by S1 in the consecutive stimuli occurred in M100 of the left
      hemisphere, whereas both M50 and M100 responses to S2 only in the right
      hemisphere reflected whether two stimuli in a pair were the same or not. Both M50
      and M100 magnitudes were different with the presenting order (S1 vs. S2) for both
      same and different conditions in the both hemispheres. CONCLUSIONS/SIGNIFICANCES:
      Our results demonstrate that the auditory response depends on timbre
      characteristics. Moreover, it was revealed that the auditory sensory gating is
      determined not by the stimulus that directly evokes the response, but rather by
      whether or not the two stimuli are identical in timbre.

PMID- 21949808
TI  - NF-kappaB induced the donor liver cold preservation related acute lung injury in
      rat liver transplantation model.
AB  - BACKGROUND: We have observed at our clinical work that acute lung injury (ALI)
      often occurs in patients transplanted with donor livers persevered for long time.
      So, we conducted this study to investigate the influence of cold preservation
      time (CPT) of donor liver on ALI induced by liver transplantation (LT), and
      further study the role of nuclear factor-kappaB (NF-kappaB) in the process.
      METHODS: Wistar rats were used as donors and recipients to establish orthotopic
      rat liver transplantation models. Donor livers were preserved at 4 degrees C for
      different lengths of time. The effect of NF-kappaB inhibitor, ammonium
      pyrrolidinedithiocarbamate (PDTC), on ALI was detected. All samples were
      harvested after 3 h reperfusion. The severity of liver injury was evaluated
      first. The expressions of tumor necrosis factor-alpha (TNF-alpha) and interleukin
      1beta (IL-1beta) in liver tissue and liver outflow serum were measured
      respectively. The severity indexes of ALI, the activity of NF-kappaB and
      inhibitor-kappaBalpha (I-kappaBalpha) in lung/liver were measured accordingly.
      RESULTS: With the prolonged liver CPT, the liver damage associated indexes and
      ALI-related indexes all increased significantly. TNF-alpha and IL-1beta in liver
      outflow serum increased accordingly, and the activity of NF-kappaB in liver/lung
      increased correspondingly. All these ALI-associated indexes could be partially
      reversed by the use of PDTC. CONCLUSIONS: Extended CPT aggravates the damage of
      donor liver and induces the expressions of TNF-alpha and IL-1beta in liver. These
      inflammatory factors migrate to lung via liver outflow blood and activate NF
      kappaB in lung, inducing ALI finally. NF-kappaB may play a critical role in LT
      related ALI. Patients with or at risk of ALI may benefit from acute anti
      inflammatory treatment with PDTC.

PMID- 21949809
TI  - Differential effects of peptidoglycan recognition proteins on experimental atopic
      and contact dermatitis mediated by Treg and Th17 cells.
AB  - Skin protects the body from the environment and is an important component of the
      innate and adaptive immune systems. Atopic dermatitis and contact dermatitis are
      among the most frequent inflammatory skin diseases and are both determined by
      multigenic predisposition, environmental factors, and aberrant immune response.
      Peptidoglycan Recognition Proteins (Pglyrps) are expressed in the skin and we
      report here that they modulate sensitivity to experimentally-induced atopic
      dermatitis and contact dermatitis. Pglyrp3(-/-) and Pglyrp4(-/-) mice (but not
      Pglyrp2(-/-) mice) develop more severe oxazolone-induced atopic dermatitis than
      wild type (WT) mice. The common mechanism underlying this increased sensitivity
      of Pglyrp3(-/-) and Pglyrp4(-/-) mice to atopic dermatitis is reduced recruitment
      of Treg cells to the skin and enhanced production and activation Th17 cells in
      Pglyrp3(-/-) and Pglyrp4(-/-) mice, which results in more severe inflammation and
      keratinocyte proliferation. This mechanism is supported by decreased inflammation
      in Pglyrp3(-/-) mice following in vivo induction of Treg cells by vitamin D or
      after neutralization of IL-17. By contrast, Pglyrp1(-/-) mice develop less severe
      oxazolone-induced atopic dermatitis and also oxazolone-induced contact dermatitis
      than WT mice. Thus, Pglyrp3 and Pglyrp4 limit over-activation of Th17 cells by
      promoting accumulation of Treg cells at the site of chronic inflammation, which
      protects the skin from exaggerated inflammatory response to cell activators and
      allergens, whereas Pglyrp1 has an opposite pro-inflammatory effect in the skin.

PMID- 21949810
TI  - A functional interface at the rDNA connects rRNA synthesis, pre-rRNA processing
      and nucleolar surveillance in budding yeast.
AB  - Ribogenesis is a multistep error-prone process that is actively monitored by
      quality control mechanisms. How ribosomal RNA synthesis, pre-rRNA processing and
      nucleolar surveillance are integrated is unclear. Nor is it understood how
      defective ribosomes are recognized. We report in budding yeast that, in vivo, the
      interaction between the transcription elongation factor Spt5 and Rpa190, the
      largest subunit of RNA polymerase (Pol) I, requires the Spt5 C-terminal region
      (CTR), a conserved and highly repetitive domain that is reminiscent of the RNA
      Pol II C-terminal domain (CTD). We show that this sequence is also required for
      the interaction between Spt5 and Nrd1, an RNA specific binding protein, and an
      exosome cofactor. Both the Spt4-Spt5, and the Nrd1-Nab3 complexes interact
      functionally with Rrp6, and colocalize at the rDNA. Mutations in the RNA binding
      domain of Nrd1, but not in its RNA Pol II CTD-interacting domain, and mutations
      in the RRM of Nab3 led to the accumulation of normal and aberrant polyadenylated
      pre-rRNAs. Altogether these results indicate that Nrd1-Nab3 contributes to
      recruiting the nucleolar surveillance to elongating polymerases to survey nascent
      rRNA transcripts.

PMID- 21949811
TI  - Plasmodium falciparum-infected erythrocytes and IL-12/IL-18 induce diverse
      transcriptomes in human NK cells: IFN-alpha/beta pathway versus TREM signaling.
AB  - The protective immunity of natural killer (NK) cells against malarial infections
      is thought to be due to early production of type II interferon (IFN) and possibly
      direct NK cell cytotoxicity. To better understand this mechanism, a microarray
      analysis was conducted on NK cells from healthy donors PBMCs that were co
      cultured with P. falciparum 3D7-infected erythrocytes. A very similar pattern of
      gene expression was observed among all donors for each treatment in three
      replicas. Parasites particularly modulated genes involved in IFN-alpha/beta
      signaling as well as molecules involved in the activation of interferon
      regulatory factors, pathways known to play a role in the antimicrobial immune
      response. This pattern of transcription was entirely different from that shown by
      NK cells treated with IL-12 and IL-18, in which IFN-gamma- and TREM-1-related
      genes were over-expressed. These results suggest that P. falciparum parasites and
      the cytokines IL-12 and IL-18 have diverse imprints on the transcriptome of human
      primary NK cells. IFN-alpha-related genes are the prominent molecules induced by
      parasites on NK cells and arise as candidate biomarkers that merit to be further
      investigated as potential new tools in malaria control.

PMID- 21949813
TI  - Prevalence of grey matter pathology in early multiple sclerosis assessed by
      magnetization transfer ratio imaging.
AB  - The aim of the study was to assess the prevalence, the distribution and the
      impact on disability of grey matter (GM) pathology in early multiple sclerosis.
      Eighty-eight patients with a clinically isolated syndrome with a high risk
      developing multiple sclerosis were included in the study. Forty-four healthy
      controls constituted the normative population. An optimized statistical mapping
      analysis was performed to compare each subject's GM Magnetization Transfer Ratio
      (MTR) imaging maps with those of the whole group of controls. The statistical
      threshold of significant GM MTR decrease was determined as the maximum p value
      (p<0.05 FDR) for which no significant cluster survived when comparing each
      control to the whole control population. Using this threshold, 51% of patients
      showed GM abnormalities compared to controls. Locally, 37% of patients presented
      abnormalities inside the limbic cortex, 34% in the temporal cortex, 32% in the
      deep grey matter, 30% in the cerebellum, 30% in the frontal cortex, 26% in the
      occipital cortex and 19% in the parietal cortex. Stepwise regression analysis
      evidenced significant association (p = 0.002) between EDSS and both GM pathology
      (p = 0.028) and T2 white matter lesions load (p = 0.019). In the present study,
      we evidenced that individual analysis of GM MTR map allowed demonstrating that GM
      pathology is highly heterogeneous across patients at the early stage of MS and
      partly underlies irreversible disability.

PMID- 21949812
TI  - Administration of simvastatin after kainic acid-induced status epilepticus
      restrains chronic temporal lobe epilepsy.
AB  - In this study, we examined the effect of chronic administration of simvastatin
      immediately after status epilepticus (SE) on rat brain with temporal lobe
      epilepsy (TLE). First, we evaluated cytokines expression at 3 days post KA-lesion
      in hippocampus and found that simvastatin-treatment suppressed lesion-induced
      expression of interleukin (IL)-1beta and tumor necrosis factor-alpha (TNF-alpha).
      Further, we quantified reactive astrocytosis using glial fibrillary acidic
      protein (GFAP) staining and neuron loss using Nissl staining in hippocampus at 4
      6 months after KA-lesion. We found that simvastatin suppressed reactive
      astrocytosis demonstrated by a significant decrease in GFAP-positive cells, and
      attenuated loss of pyramidal neurons in CA3 and interneurons in dentate hilar
      (DH). We next assessed aberrant mossy fiber sprouting (MFS) that is known to
      contribute to recurrence of spontaneous seizure in epileptic brain. In contrast
      to the robust MFS observed in saline-treated animals, the extent of MFS was
      restrained by simvastatin in epileptic rats. Attenuated MFS was related to
      decreased neuronal loss in CA3 and DH, which is possibly a mechanism underlying
      decreased hippocampal susceptibility in animal treated with simvastatin.
      Electronic encephalography (EEG) was recorded during 4 to 6 months after KA
      lesion. The frequency of abnormal spikes in rats with simvastatin-treatment
      decreased significantly compared to the saline group. In summary, simvastatin
      treatment suppressed cytokines expression and reactive astrocytosis and decreased
      the frequency of discharges of epileptic brain, which might be due to the
      inhibition of MFS in DH. Our study suggests that simvastatin administration might
      be a possible intervention and promising strategy for preventing SE exacerbating
      to chronic epilepsy.

PMID- 21949814
TI  - West Nile virus replication requires fatty acid synthesis but is independent on
      phosphatidylinositol-4-phosphate lipids.
AB  - West Nile virus (WNV) is a neurovirulent mosquito-borne flavivirus, which main
      natural hosts are birds but it also infects equines and humans, among other
      mammals. As in the case of other plus-stranded RNA viruses, WNV replication is
      associated to intracellular membrane rearrangements. Based on results obtained
      with a variety of viruses, different cellular processes have been shown to play
      important roles on these membrane rearrangements for efficient viral replication.
      As these processes are related to lipid metabolism, fatty acid synthesis, as well
      as generation of a specific lipid microenvironment enriched in
      phosphatidylinositol-4-phosphate (PI4P), has been associated to it in other viral
      models. In this study, intracellular membrane rearrangements following infection
      with a highly neurovirulent strain of WNV were addressed by means of electron and
      confocal microscopy. Infection of WNV, and specifically viral RNA replication,
      were dependent on fatty acid synthesis, as revealed by the inhibitory effect of
      cerulenin and C75, two pharmacological inhibitors of fatty acid synthase, a key
      enzyme of this process. However, WNV infection did not induce redistribution of
      PI4P lipids, and PI4P did not localize at viral replication complex. Even more,
      WNV multiplication was not inhibited by the use of the phosphatidylinositol-4
      kinase inhibitor PIK93, while infection by the enterovirus Coxsackievirus B5 was
      reduced. Similar features were found when infection by other flavivirus, the
      Usutu virus (USUV), was analyzed. These features of WNV replication could help to
      design specific antiviral approaches against WNV and other related flaviviruses.

PMID- 21949815
TI  - T cell-intrinsic and -extrinsic contributions of the IFNAR/STAT1-axis to
      thymocyte survival.
AB  - STAT1 is an essential part of interferon signaling, and STAT1-deficiency results
      in heightened susceptibility to infections or autoimmunity in both mice and
      humans. Here we report that mice lacking the IFNalpha/beta-receptor (IFNAR1) or
      STAT1 display impaired deletion of autoreactive CD4(+)CD8(+)-T-cells. Strikingly,
      co-existence of WT T cells restored thymic elimination of self-reactive STAT1
      deficient CD4(+)CD8(+)-T cells. Analysis of STAT1-deficient thymocytes further
      revealed reduced Bim expression, which was restored in the presence of WT T
      cells. These results indicate that type I interferons and STAT1 play an important
      role in the survival of MHC class I-restricted T cells in a T cell intrinsic and
      non-cell intrinsic manner that involves regulation of Bim expression through
      feedback provided by mature STAT1-competent T cells.

PMID- 21949816
TI  - Clonal evolution through loss of chromosomes and subsequent polyploidization in
      chondrosarcoma.
AB  - Near-haploid chromosome numbers have been found in less than 1% of
      cytogenetically reported tumors, but seem to be more common in certain neoplasms
      including the malignant cartilage-producing tumor chondrosarcoma. By a literature
      survey of published karyotypes from chondrosarcomas we could confirm that loss of
      chromosomes resulting in hyperhaploid-hypodiploid cells is common and that these
      cells may polyploidize. Sixteen chondrosarcomas were investigated by single
      nucleotide polymorphism (SNP) array and the majority displayed SNP patterns
      indicative of a hyperhaploid-hypodiploid origin, with or without subsequent
      polyploidization. Except for chromosomes 5, 7, 19, 20 and 21, autosomal loss of
      heterozygosity was commonly found, resulting from chromosome loss and subsequent
      duplication of monosomic chromosomes giving rise to uniparental disomy.
      Additional gains, losses and rearrangements of genetic material, and even
      repeated rounds of polyploidization, may affect chondrosarcoma cells resulting in
      highly complex karyotypes. Loss of chromosomes and subsequent polyploidization
      was not restricted to a particular chondrosarcoma subtype and, although commonly
      found in chondrosarcoma, binucleated cells did not seem to be involved in these
      events.

PMID- 21949817
TI  - An integrated PCR colony hybridization approach to screen cDNA libraries for full
      length coding sequences.
AB  - BACKGROUND: cDNA-Amplified Fragment Length Polymorphism (cDNA-AFLP) is a commonly
      used technique for genome-wide expression analysis that does not require prior
      sequence knowledge. Typically, quantitative expression data and sequence
      information are obtained for a large number of differentially expressed gene
      tags. However, most of the gene tags do not correspond to full-length (FL) coding
      sequences, which is a prerequisite for subsequent functional analysis.
      METHODOLOGY: A medium-throughput screening strategy, based on integration of
      polymerase chain reaction (PCR) and colony hybridization, was developed that
      allows in parallel screening of a cDNA library for FL clones corresponding to
      incomplete cDNAs. The method was applied to screen for the FL open reading frames
      of a selection of 163 cDNA-AFLP tags from three different medicinal plants,
      leading to the identification of 109 (67%) FL clones. Furthermore, the protocol
      allows for the use of multiple probes in a single hybridization event, thus
      significantly increasing the throughput when screening for rare transcripts.
      CONCLUSIONS: The presented strategy offers an efficient method for the conversion
      of incomplete expressed sequence tags (ESTs), such as cDNA-AFLP tags, to FL
      coding sequences.

PMID- 21949818
TI  - Out of the Pacific and back again: insights into the matrilineal history of
      Pacific killer whale ecotypes.
AB  - Killer whales (Orcinus orca) are the most widely distributed marine mammals and
      have radiated to occupy a range of ecological niches. Disparate sympatric types
      are found in the North Atlantic, Antarctic and North Pacific oceans, however,
      little is known about the underlying mechanisms driving divergence. Previous
      phylogeographic analysis using complete mitogenomes yielded a bifurcating tree of
      clades corresponding to described ecotypes. However, there was low support at two
      nodes at which two Pacific and two Atlantic clades diverged. Here we apply
      further phylogenetic and coalescent analyses to partitioned mitochondrial genome
      sequences to better resolve the pattern of past radiations in this species. Our
      phylogenetic reconstructions indicate that in the North Pacific, sympatry between
      the maternal lineages that make up each ecotype arises from secondary contact.
      Both the phylogenetic reconstructions and a clinal decrease in diversity suggest
      a North Pacific to North Atlantic founding event, and the later return of killer
      whales to the North Pacific. Therefore, ecological divergence could have occurred
      during the allopatric phase through drift or selection and/or may have either
      commenced or have been consolidated upon secondary contact due to resource
      competition. The estimated timing of bidirectional migration between the North
      Pacific and North Atlantic coincided with the previous inter-glacial when the
      leakage of fauna from the Indo-Pacific into the Atlantic via the Agulhas current
      was particularly vigorous.

PMID- 21949819
TI  - Multi-locus variable-number tandem repeat profiling of Salmonella enterica
      serovar Typhi isolates from blood cultures and gallbladder specimens from
      Makassar, South-Sulawesi, Indonesia.
AB  - Multi-locus variable-number tandem repeat analysis differentiated 297 Salmonella
      enterica serovar Typhi blood culture isolates from Makassar in 76 genotypes and a
      single unique S. Typhi genotype was isolated from the cholecystectomy specimens
      of four patients with cholelithiasis. The high diversity in S. Typhi genotypes
      circulating in Makassar indicates that the number of carriers could be very
      large, which may complicate disease prevention and control.

PMID- 21949820
TI  - Evolutionary genomics of a temperate bacteriophage in an obligate intracellular
      bacteria (Wolbachia).
AB  - Genome evolution of bacteria is usually influenced by ecology, such that bacteria
      with a free-living stage have large genomes and high rates of horizontal gene
      transfer, while obligate intracellular bacteria have small genomes with typically
      low amounts of gene exchange. However, recent studies indicate that obligate
      intracellular species that host-switch frequently harbor agents of horizontal
      transfer such as mobile elements. For example, the temperate double-stranded DNA
      bacteriophage WO in Wolbachia persistently transfers between bacterial
      coinfections in the same host. Here we show that despite the phage's rampant
      mobility between coinfections, the prophage's genome displays features of
      constraint related to its intracellular niche. First, there is always at least
      one intact prophage WO and usually several degenerate, independently-acquired WO
      prophages in each Wolbachia genome. Second, while the prophage genomes are
      modular in composition with genes of similar function grouping together, the
      modules are generally not interchangeable with other unrelated phages and thus do
      not evolve by the Modular Theory. Third, there is an unusual core genome that
      strictly consists of head and baseplate genes; other gene modules are frequently
      deleted. Fourth, the prophage recombinases are diverse and there is no conserved
      integration sequence. Finally, the molecular evolutionary forces acting on
      prophage WO are point mutation, intragenic recombination, deletion, and purifying
      selection. Taken together, these analyses indicate that while lateral transfer of
      phage WO is pervasive between Wolbachia with occasional new gene uptake,
      constraints of the intracellular niche obstruct extensive mixture between WO and
      the global phage population. Although the Modular Theory has long been considered
      the paradigm of temperate bacteriophage evolution in free-living bacteria, it
      appears irrelevant in phages of obligate intracellular bacteria.

PMID- 21949821
TI  - Movement protein Pns6 of rice dwarf phytoreovirus has both ATPase and RNA binding
      activities.
AB  - Cell-to-cell movement is essential for plant viruses to systemically infect host
      plants. Plant viruses encode movement proteins (MP) to facilitate such movement.
      Unlike the well-characterized MPs of DNA viruses and single-stranded RNA (ssRNA)
      viruses, knowledge of the functional mechanisms of MPs encoded by double-stranded
      RNA (dsRNA) viruses is very limited. In particular, many studied MPs of DNA and
      ssRNA viruses bind non-specifically ssRNAs, leading to models in which
      ribonucleoprotein complexes (RNPs) move from cell to cell. Thus, it will be of
      special interest to determine whether MPs of dsRNA viruses interact with genomic
      dsRNAs or their derivative sRNAs. To this end, we studied the biochemical
      functions of MP Pns6 of Rice dwarf phytoreovirus (RDV), a member of Phytoreovirus
      that contains a 12-segmented dsRNA genome. We report here that Pns6 binds both
      dsRNAs and ssRNAs. Intriguingly, Pns6 exhibits non-sequence specificity for dsRNA
      but shows preference for ssRNA sequences derived from the conserved genomic 5'-
      and 3'-terminal consensus sequences of RDV. Furthermore, Pns6 exhibits magnesium
      dependent ATPase activities. Mutagenesis identified the RNA binding and ATPase
      activity sites of Pns6 at the N- and C-termini, respectively. Our results
      uncovered the novel property of a viral MP in differentially recognizing dsRNA
      and ssRNA and establish a biochemical basis to enable further studies on the
      mechanisms of dsRNA viral MP functions.

PMID- 21949824
TI  - Can differences in host behavior drive patterns of disease prevalence in
      tadpoles?
AB  - Differences in host behavior and resistance to disease can influence the outcome
      of host-pathogen interactions. We capitalized on the variation in aggregation
      behavior of Fowler's toads (Anaxyrus [ = Bufo] fowleri) and grey treefrogs (Hyla
      versicolor) tadpoles and tested for differences in transmission of
      Batrachochytrium dendrobatidis (Bd) and host-specific fitness consequences (i.e.,
      life history traits that imply fitness) of infection in single-species amphibian
      mesocosms. On average, A. fowleri mesocosms supported higher Bd prevalences and
      infection intensities relative to H. versicolor mesocosms. Higher Bd prevalence
      in A. fowleri mesocosms may result, in part, from higher intraspecific
      transmission due to the aggregation of tadpoles raised in Bd treatments. We also
      found that, independent of species, tadpoles raised in the presence of Bd were
      smaller and less developed than tadpoles raised in disease-free conditions. Our
      results indicate that aggregation behavior might increase Bd prevalence and that
      A. fowleri tadpoles carry heavier infections relative to H. versicolor tadpoles.
      However, our results demonstrate that Bd appears to negatively impact larval
      growth and developmental rates of A. fowleri and H. versicolor similarly, even in
      the absence of high Bd prevalence.

PMID- 21949822
TI  - Functional polymorphisms in the TERT promoter are associated with risk of serous
      epithelial ovarian and breast cancers.
AB  - Genetic variation at the TERT-CLPTM1L locus at 5p15.33 is associated with
      susceptibility to several cancers, including epithelial ovarian cancer (EOC). We
      have carried out fine-mapping of this region in EOC which implicates an
      association with a single nucleotide polymorphism (SNP) within the TERT promoter.
      We demonstrate that the minor alleles at rs2736109, and at an additional TERT
      promoter SNP, rs2736108, are associated with decreased breast cancer risk, and
      that the combination of both SNPs substantially reduces TERT promoter activity.

PMID- 21949823
TI  - Differences in the number of intrinsically disordered regions between yeast
      duplicated proteins, and their relationship with functional divergence.
AB  - BACKGROUND: Intrinsically disordered regions are enriched in short interaction
      motifs that play a critical role in many protein-protein interactions. Since new
      short interaction motifs may easily evolve, they have the potential to rapidly
      change protein interactions and cellular signaling. In this work we examined the
      dynamics of gain and loss of intrinsically disordered regions in duplicated
      proteins to inspect if changes after genome duplication can create functional
      divergence. For this purpose we used Saccharomyces cerevisiae and the outgroup
      species Lachancea kluyveri. PRINCIPAL FINDINGS: We find that genes duplicated as
      part of a genome duplication (ohnologs) are significantly more intrinsically
      disordered than singletons (p<2.2(e)-16, Wilcoxon), reflecting a preference for
      retaining intrinsically disordered proteins in duplicate. In addition, there have
      been marked changes in the extent of intrinsic disorder following duplication. A
      large number of duplicated genes have more intrinsic disorder than their L.
      kluyveri ortholog (29% for duplicates versus 25% for singletons) and an even
      greater number have less intrinsic disorder than the L. kluyveri ortholog (37%
      for duplicates versus 25% for singletons). Finally, we show that the number of
      physical interactions is significantly greater in the more intrinsically
      disordered ohnolog of a pair (p = 0.003, Wilcoxon). CONCLUSION: This work shows
      that intrinsic disorder gain and loss in a protein is a mechanism by which a
      genome can also diverge and innovate. The higher number of interactors for
      proteins that have gained intrinsic disorder compared with their duplicates may
      reflect the acquisition of new interaction partners or new functional roles.

PMID- 21949826
TI  - Short Stat5-interacting peptide derived from phospholipase C-beta3 inhibits
      hematopoietic cell proliferation and myeloid differentiation.
AB  - Constitutive activation of the transcription factor Stat5 in hematopoietic
      stem/progenitor cells leads to various hematopoietic malignancies including
      myeloproliferative neoplasm (MPN). Our recent study found that phospholipase C
      (PLC)-beta3 is a novel tumor suppressor involved in MPN, lymphoma and other
      tumors. Stat5 activity is negatively regulated by the SH2 domain-containing
      protein phosphatase SHP-1 in a PLC-beta3-dependent manner. PLC-beta3 can form the
      multimolecular SPS complex together with SHP-1 and Stat5. The close physical
      proximity of SHP-1 and Stat5 brought about by interacting with the C-terminal
      segment of PLC-beta3 (PLC-beta3-CT) accelerates SHP-1-mediated dephosphorylation
      of Stat5. Here we identify the minimal sequences within PLC-beta3-CT required for
      its tumor suppressor function. Two of the three Stat5-binding noncontiguous
      regions, one of which also binds SHP-1, substantially inhibited in vitro
      proliferation of Ba/F3 cells. Surprisingly, an 11-residue Stat5-binding peptide
      (residues 988-998) suppressed Stat5 activity in Ba/F3 cells and in vivo
      proliferation and myeloid differentiation of hematopoietic stem/progenitor cells.
      Therefore, this study further defines PLC-beta3-CT as the Stat5- and SHP-1
      binding domain by identifying minimal functional sequences of PLC-beta3 for its
      tumor suppressor function and implies their potential utility in the control of
      hematopoietic malignancies.

PMID- 21949825
TI  - Distinct populations of hepatic stellate cells in the mouse liver have different
      capacities for retinoid and lipid storage.
AB  - Hepatic stellate cell (HSC) lipid droplets are specialized organelles for the
      storage of retinoid, accounting for 50-60% of all retinoid present in the body.
      When HSCs activate, retinyl ester levels progressively decrease and the lipid
      droplets are lost. The objective of this study was to determine if the HSC
      population in a healthy, uninjured liver demonstrates heterogeneity in its
      capacity for retinoid and lipid storage in lipid droplets. To this end, we
      utilized two methods of HSC isolation, which leverage distinct properties of
      these cells, including their vitamin A content and collagen expression. HSCs were
      isolated either from wild type (WT) mice in the C57BL/6 genetic background by
      flotation in a Nycodenz density gradient, followed by fluorescence activated cell
      sorting (FACS) based on vitamin A autofluorescence, or from collagen-green
      fluorescent protein (GFP) mice by FACS based on GFP expression from a GFP
      transgene driven by the collagen I promoter. We show that GFP-HSCs have: (i)
      increased expression of typical markers of HSC activation; (ii) decreased retinyl
      ester levels, accompanied by reduced expression of the enzyme needed for hepatic
      retinyl ester synthesis (LRAT); (iii) decreased triglyceride levels; (iv)
      increased expression of genes associated with lipid catabolism; and (v) an
      increase in expression of the retinoid-catabolizing cytochrome, CYP2S1.
      CONCLUSION: Our observations suggest that the HSC population in a healthy,
      uninjured liver is heterogeneous. One subset of the total HSC population, which
      expresses early markers of HSC activation, may be "primed" and ready for rapid
      response to acute liver injury.

PMID- 21949827
TI  - A targeted association study of immunity genes and networks suggests novel
      associations with placental malaria infection.
AB  - A large proportion of the death toll associated with malaria is a consequence of
      malaria infection during pregnancy, causing up to 200,000 infant deaths annually.
      We previously published the first extensive genetic association study of
      placental malaria infection, and here we extend this analysis considerably,
      investigating genetic variation in over 9,000 SNPs in more than 1,000 genes
      involved in immunity and inflammation for their involvement in susceptibility to
      placental malaria infection. We applied a new approach incorporating results from
      both single gene analysis as well as gene-gene interactions on a protein-protein
      interaction network. We found suggestive associations of variants in the gene
      KLRK1 in the single gene analysis, as well as evidence for associations of
      multiple members of the IL-7/IL-7R signalling cascade in the combined analysis.
      To our knowledge, this is the first large-scale genetic study on placental
      malaria infection to date, opening the door for follow-up studies trying to
      elucidate the genetic basis of this neglected form of malaria.

PMID- 21949828
TI  - Phylogenetic and pathotypical analysis of two virulent Newcastle disease viruses
      isolated from domestic ducks in China.
AB  - Two velogenic Newcastle disease viruses (NDV) obtained from outbreaks in domestic
      ducks in China were characterized in this study. Phylogenetic analysis revealed
      that both strains clustered with the class II viruses, with one phylogenetically
      close to the genotype VII NDVs and the other closer to genotype IX. The deduced
      amino acid sequence of the cleavage site of the fusion (F) protein confirmed that
      both isolates contained the virulent motif (112)RRQK/RRF(117) at the cleavage
      site. The two NDVs had severe pathogenicity in fully susceptible chickens,
      resulting in 100% mortality. One of the isolates also demonstrated some
      pathogenicity in domestic ducks. The present study suggests that more than one
      genotype of NDV circulates in domestic ducks in China and viral transmission may
      occur among chickens and domestic ducks.

PMID- 21949829
TI  - Sexually selected infanticide in a polygynous bat.
AB  - BACKGROUND: Adult individuals of many species kill unrelated conspecific infants
      for several adaptive reasons ranging from predation or resource competition to
      the prevention of misdirected parental care. Moreover, infanticide can increase
      the reproductive success of the aggressor by killing the offspring of competitors
      and thereafter mating with the victimized females. This sexually selected
      infanticide predominantly occurs in polygynous species, with convincing evidence
      for primates, carnivores, equids, and rodents. Evidence for bats was predicted
      but lacking. METHODOLOGY/PRINCIPAL FINDINGS: Here we report the first case, to
      our knowledge, of sexually selected infanticide in a bat, the polygynous white
      throated round-eared bat, Lophostoma silvicolum. Behavioral studies in a free
      living population revealed that an adult male repeatedly attacked and injured the
      pups of two females belonging to his harem, ultimately causing the death of one
      pup. The infanticidal male subsequently mated with the mother of the victimized
      pup and this copulation occurred earlier than any other in his harem.
      CONCLUSIONS/SIGNIFICANCE: Our findings indicate that sexually selected
      infanticide is more widespread than previously thought, adding bats as a new
      taxon performing this strategy. Future work on other bats, especially polygynous
      species in the tropics, has great potential to investigate the selective
      pressures influencing the evolution of sexually selected infanticide and to study
      how infanticide impacts reproductive strategies and social structures of
      different species.

PMID- 21949830
TI  - Self-rated health as a predictor of disability retirement--the contribution of
      ill-health and working conditions.
AB  - OBJECTIVE: Self-rated health is a generic health indicator predicting mortality,
      many diseases, and need for care. We examined self-rated health as a predictor of
      subsequent disability retirement, and ill-health and working conditions as
      potential explanations for the association. METHODS: Self-rated health and the
      covariates were obtained from the Helsinki Health Study baseline mail surveys in
      2000-2002 conducted among municipal employees aged 40-60 years (n = 6525). Data
      for disability retirement events (n = 625) along with diagnoses were linked from
      the Finnish Centre for Pensions, with a follow-up by the end of 2010. Hazard
      ratios (HR) and their 95% confidence intervals (CI) were calculated using
      competing risks models. RESULTS: Less than good self-rated health predicted
      disability retirement due to all causes among both women (HR = 4.60, 95% CI =
      3.84-5.51) and men (HR = 3.83, 95% CI = 2.64-5.56), as well as due to
      musculoskeletal diseases (HR = 5.17, 95% CI = 4.02-6.66) and mental disorders (HR
      = 4.80, 95% CI = 3.50-6.59) among women and men pooled. Ill-health and physical
      working conditions partly explained the found associations, which nevertheless
      remained after the adjustments. Among the measures of ill-health limiting long
      standing illness explained the association most in all-cause disability
      retirement and disability retirements due to musculoskeletal diseases, whereas
      common mental disorders explained the association most in disability retirements
      due to mental health disorders. Among working conditions physical work load and
      hazardous exposures at work explained the association most, although much less
      than ill-health. CONCLUSIONS: Self-rated health is a strong predictor of
      disability retirement. This can be partly explained by ill-health and working
      conditions. Poor self-rated health provides a useful marker for increased risk of
      work disability and subsequent disability retirement.

PMID- 21949831
TI  - Structural basis for distinct binding properties of the human galectins to
      Thomsen-Friedenreich antigen.
AB  - The Thomsen-Friedenreich (TF or T) antigen, Galbeta1-3GalNAcalpha1-O-Ser/Thr, is
      the core 1 structure of O-linked mucin type glycans appearing in tumor-associated
      glycosylation. The TF antigen occurs in about 90% of human cancer cells and is a
      potential ligand for the human endogenous galectins. It has been reported that
      human galectin-1 (Gal-1) and galectin-3 (Gal-3) can perform their cancer-related
      functions via specifically recognizing TF antigen. However, the detailed binding
      properties have not been clarified and structurally characterized. In this work,
      first we identified the distinct TF-binding abilities of Gal-1 and Gal-3. The
      affinity to TF antigen for Gal-3 is two orders of magnitude higher than that for
      Gal-1. The structures of Gal-3 carbohydrate recognition domain (CRD) complexed
      with TF antigen and derivatives, TFN and GM1, were then determined. These
      structures show a unique Glu-water-Arg-water motif-based mode as previously
      observed in the mushroom galectin AAL. The observation demonstrates that this
      recognition mode is commonly adopted by TF-binding galectins, either as
      endogenous or exogenous ones. The detailed structural comparisons between Gal-1
      and Gal-3 CRD and mutagenesis experiments reveal that a pentad residue motif
      ((51)AHGDA(55)) at the loop (g1-L4) connecting beta-strands 4 and 5 of Gal-1
      produces a serious steric hindrance for TF binding. This motif is the main
      structural basis for Gal-1 with the low affinity to TF antigen. These findings
      provide the intrinsic structural elements for regulating the TF-binding activity
      of Gal-1 in some special conditions and also show certain target and approach for
      mediating some tumor-related bioactivities of human galectins.

PMID- 21949832
TI  - Akt regulates IL-10 mediated suppression of TNFalpha-induced cardiomyocyte
      apoptosis by upregulating Stat3 phosphorylation.
AB  - BACKGROUND: We have already reported that TNF-alpha increases cardiomyocyte
      apoptosis and IL-10 treatment prevented these effects of TNF-alpha. Present study
      investigates the role of Akt and Jak/Stat pathway in the IL-10 modulation of TNF
      alpha induced cardiomyocyte apoptosis. METHODOLOGY/PRINCIPAL FINDINGS:
      Cardiomyocytes isolated from adult Sprague Dawley rats were exposed to TNF-alpha
      (10 ng/ml), IL-10 (10 ng/ml) and TNF-alpha+IL-10 (ratio 1) for 4 h. Exposure to
      TNF-alpha resulted in an increase in cardiomyocyte apoptosis as measured by flow
      cytometry and TUNEL assay. IL-10 by itself had no effect, but it prevented TNF
      alpha induced apoptosis. IL-10 treatment increased Akt levels within
      cardiomyocytes and this change was associated with an increase in Jak1 and Stat3
      phosphorylation. Pre-exposure of cells to Akt inhibitor prevented IL-10 induced
      Stat3 phosphorylation. Furthermore, in the presence of Akt or Stat3 inhibitor, IL
      10 treatment was unable to block TNF-alpha induced cardiomyocyte apoptosis.
      CONCLUSION: It is suggested that IL-10 modulation of TNF-alpha induced
      cardiomyocyte apoptosis is mediated by Akt via Stat3 activation.

PMID- 21949833
TI  - Puerarin suppresses invasion and vascularization of endometriosis tissue
      stimulated by 17beta-estradiol.
AB  - BACKGROUND: Puerarin, a phytoestrogen with a weak estrogenic effect, binds to
      estrogen receptors, thereby competing with 17beta-estradiol (E2) and producing an
      anti-estrogenic effect. This study was to investigate whether puerarin could
      suppress the invasion and vascularization of E2-stimulated endometriotic tissue.
      METHODOLOGY/PRINCIPAL FINDINGS: The endometriotic stromal cells (ESCs) were
      successfully established and their invasive ability under different treatments
      was assessed through a Transwell Assay. Simultaneously, matrix metallopeptidase 9
      (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) were detected by
      western blotting. Vascularization of endometriotic tissues was observed by
      chicken chorioallantoic membrane (CAM) assay. The staining of MMP-9,
      intercellular adhesion molecule 1 (ICAM-1), TIMP-1, and vascular endothelial
      growth factor (VEGF) in grafted endometriotic tissues was examined using
      immunohistochemistry analysis. The purity of ESCs in isolated cells was >95%, as
      determined by the fluoroimmunoassay of vimentin. E2 (10(-8) mol/L) promoted the
      invasiveness of ESCs by increasing MMP-9 accumulation and decreasing TIMP-1
      accumulation. Interestingly, puerarin (10(-9) mol/L) significantly reversed these
      effects (P<0.01). The CAM assay indicated that puerarin (10(-9) mol/L) also
      inhibited the angiopoiesis of endometriotic tissue stimulated by the E2 (10(-8)
      mol/L) treatment (P<0.05). Accordingly, immunohistochemistry showed that the
      accumulation of MMP-9, ICAM-1, and VEGF was reduced whereas that of TIMP-1
      increased in the combination treatment group compared with the E2 treatment
      group. CONCLUSIONS/SIGNIFICANCE: This study demonstrated that puerarin could
      suppress the tissue invasion by ESCs and the vascularization of ectopic
      endometrial tissues stimulated by E2, suggesting that puerarin may be a potential
      drug for the treatment of endometriosis.

PMID- 21949834
TI  - Mutation in utp15 disrupts vascular patterning in a p53-dependent manner in
      zebrafish embryos.
AB  - BACKGROUND: Angiogenesis is the process by which the highly branched and
      functional vasculature arises from the major vessels, providing developing
      tissues with nutrients, oxygen, and removing metabolic waste. During
      embryogenesis, vascular patterning is dependent on a tightly regulated balance
      between pro- and anti-angiogenic signals, and failure of angiogenesis leads to
      embryonic lethality. Using the zebrafish as a model organism, we sought to
      identify genes that influence normal vascular patterning. METHODOLOGY AND
      PRINCIPAL FINDINGS: In a forward genetic screen, we identified mutant LA1908,
      which manifests massive apoptosis during early embryogenesis, abnormal expression
      of several markers of arterial-venous specification, delayed angiogenic sprouting
      of the intersegmental vessels (ISV), and malformation of the caudal vein plexus
      (CVP), indicating a critical role for LA1908 in cell survival and angiogenesis.
      Genetic mapping and sequencing identified a G to A transition in the splice site
      preceding exon 11 of utp15 in LA1908 mutant embryos. Overexpression of wild type
      utp15 mRNA suppresses all observed mutant phenotypes, demonstrating a causative
      relationship between utp15 and LA1908. Furthermore, we found that injecting
      morpholino oligonucleotides inhibiting p53 translation prevents cell death and
      rescues the vascular abnormalities, indicating that p53 is downstream of Utp15
      deficiency in mediating the LA1908 phenotypes. CONCLUSIONS AND SIGNIFICANCE:
      Taken together, our data demonstrate an early embryonic effect of Utp15
      deficiency on cell survival and the normal patterning of the vasculature and
      highlight an anti-angiogenic role of p53 in developing embryos.

PMID- 21949835
TI  - TRPV1 marks synaptic segregation of multiple convergent afferents at the rat
      medial solitary tract nucleus.
AB  - TRPV1 receptors are expressed on most but not all central terminals of cranial
      visceral afferents in the caudal solitary tract nucleus (NTS). TRPV1 is
      associated with unmyelinated C-fiber afferents. Both TRPV1+ and TRPV1- afferents
      enter NTS but their precise organization remains poorly understood. In horizontal
      brainstem slices, we activated solitary tract (ST) afferents and recorded ST
      evoked glutamatergic excitatory synaptic currents (ST-EPSCs) under whole cell
      voltage clamp conditions from neurons of the medial subnucleus. Electrical shocks
      to the ST produced fixed latency EPSCs (jitter<200 us) that identified direct ST
      afferent innervation. Graded increases in shock intensity often recruited more
      than one ST afferent and ST-EPSCs had consistent threshold intensity, latency to
      onset, and unique EPSC waveforms that characterized each unitary ST afferent
      contact. The TRPV1 agonist capsaicin (100 nM) blocked the evoked TRPV1+ ST-EPSCs
      and defined them as either TRPV1+ or TRPV1- inputs. No partial responses to
      capsaicin were observed so that in NTS neurons that received one or multiple (2
      5) direct ST afferent inputs--all were either blocked by capsaicin or were
      unaltered. Since TRPV1 mediates asynchronous release following TRPV1+ ST-evoked
      EPSCs, we likewise found that recruiting more than one ST afferent further
      augmented the asynchronous response and was eliminated by capsaicin. Thus, TRPV1+
      and TRPV1- afferents are completely segregated to separate NTS neurons. As a
      result, the TRPV1 receptor augments glutamate release only within unmyelinated
      afferent pathways in caudal medial NTS and our work indicates a complete
      separation of C-type from A-type afferent information at these first central
      neurons.

PMID- 21949836
TI  - Post-streptococcal antibodies are associated with metabolic syndrome in a
      population-based cohort.
AB  - BACKGROUND: Streptococcal infections are known to trigger autoimmune disorders,
      affecting millions worldwide. Recently, we found an association between post
      streptococcal autoantibodies against Protein Disulphide Isomerase (PDI), an
      enzyme involved in insulin degradation and insulin resistance. This led us to
      evaluate associations between post-streptococcal antibodies and metabolic
      syndrome, as defined by the updated National Cholesterol Education Program
      definition, 2005. METHODS AND FINDINGS: Metabolic data (HDL, triglycerides,
      fasting glucose, blood pressure, waist circumference, BMI, smoking), post
      streptococcal antibodies (anti-Streptolysin O (ASO) and anti-PDI), and C-reactive
      protein (CRP, as a general inflammatory marker), were assessed in 1156
      participants of the Wisconsin Sleep Cohort Study. Anti-PDI antibodies were found
      in 308 participants (26.6%), ASO>=100 in 258 (22.3%), and 482 (41.7%) met
      diagnostic criteria for metabolic syndrome. Anti-PDI antibodies but not ASO were
      significantly associated with metabolic syndrome [n = 1156, OR 1.463 (95% CI
      1.114, 1.920), p = 0.0062; adjusted for age, gender, education, smoking].
      Importantly, the anti-PDI-metabolic syndrome association remained significant
      after adjusting for CRP and fasting insulin. CONCLUSIONS: Post-streptococcal anti
      PDI antibodies are associated with metabolic syndrome regardless of fasting
      insulin and CRP levels. Whereas these data are in line with a growing body of
      evidence linking infections, immunity and metabolism, additional studies are
      necessary to establish the post-streptococcal-metabolic syndrome association.

PMID- 21949837
TI  - Sequence diversity within the capsular genes of Streptococcus pneumoniae
      serogroup 6 and 19.
AB  - The main virulence factor of Streptococcus pneumoniae is the capsule. The
      polysaccharides comprising this capsule are encoded by approximately 15 genes and
      differences in these genes result in different serotypes. The aim of this study
      was to investigate the sequence diversity of the capsular genes of serotypes 6A,
      6B, 6C, 19A and 19F and to explore a possible effect of vaccination on variation
      and distribution of these serotypes in the Netherlands. The complete capsular
      gene locus was sequenced for 25 serogroup 6 and for 20 serogroup 19 isolates. If
      one or more genes varied in 10 or more base pairs from the reference sequence, it
      was designated as a capsular subtype. Allele-specific PCRs and specific gene
      sequencing of highly variable capsular genes were performed on 184 serogroup 6
      and 195 serogroup 19 isolates to identify capsular subtypes. This revealed the
      presence of 6, 3 and a single capsular subtype within serotypes 6A, 6B and 6C,
      respectively. The serotype 19A and 19F isolates comprised 3 and 4 capsular
      subtypes, respectively. For serogroup 6, the genetic background, as determined by
      multi locus sequence typing (MLST) and multiple-locus variable number of tandem
      repeat analysis (MLVA), seemed to be closely related to the capsular subtypes,
      but this was less pronounced for serogroup 19 isolates. The data also suggest
      shifts in the occurrence of capsular subtypes within serotype 6A and 19A after
      introduction of the 7-valent pneumococcal vaccine. The shifts within these non
      vaccine serotypes might indicate that these capsular subtypes are filling the
      niche of the vaccine serotypes. In conclusion, there is considerable DNA sequence
      variation of the capsular genes within pneumococcal serogroup 6 and 19. Such
      changes may result in altered polysaccharides or in strains that produce more
      capsular polysaccharides. Consequently, these altered capsules may be less
      sensitive for vaccine induced immunity.

PMID- 21949839
TI  - Coral uptake of inorganic phosphorus and nitrogen negatively affected by
      simultaneous changes in temperature and pH.
AB  - The effects of ocean acidification and elevated seawater temperature on coral
      calcification and photosynthesis have been extensively investigated over the last
      two decades, whereas they are still unknown on nutrient uptake, despite their
      importance for coral energetics. We therefore studied the separate and combined
      impacts of increases in temperature and pCO(2) on phosphate, ammonium, and
      nitrate uptake rates by the scleractinian coral S. pistillata. Three experiments
      were performed, during 10 days i) at three pH(T) conditions (8.1, 7.8, and 7.5)
      and normal temperature (26 degrees C), ii) at three temperature conditions (26
      degrees , 29 degrees C, and 33 degrees C) and normal pH(T) (8.1), and iii) at
      three pH(T) conditions (8.1, 7.8, and 7.5) and elevated temperature (33 degrees
      C). After 10 days of incubation, corals had not bleached, as protein,
      chlorophyll, and zooxanthellae contents were the same in all treatments. However,
      photosynthetic rates significantly decreased at 33 degrees C, and were further
      reduced for the pH(T) 7.5. The photosynthetic efficiency of PSII was only
      decreased by elevated temperature. Nutrient uptake rates were not affected by a
      change in pH alone. Conversely, elevated temperature (33 degrees C) alone induced
      an increase in phosphate uptake but a severe decrease in nitrate and ammonium
      uptake rates, even leading to a release of nitrogen into seawater. Combination of
      high temperature (33 degrees C) and low pH(T) (7.5) resulted in a significant
      decrease in phosphate and nitrate uptake rates compared to control corals (26
      degrees C, pH(T) = 8.1). These results indicate that both inorganic nitrogen and
      phosphorus metabolism may be negatively affected by the cumulative effects of
      ocean warming and acidification.

PMID- 21949838
TI  - Mutations in protein-binding hot-spots on the hub protein Smad3 differentially
      affect its protein interactions and Smad3-regulated gene expression.
AB  - BACKGROUND: Hub proteins are connected through binding interactions to many other
      proteins. Smad3, a mediator of signal transduction induced by transforming growth
      factor beta (TGF-beta), serves as a hub protein for over 50 protein-protein
      interactions. Different cellular responses mediated by Smad3 are the product of
      cell-type and context dependent Smad3-nucleated protein complexes acting in
      concert. Our hypothesis is that perturbation of this spectrum of protein
      complexes by mutation of single protein-binding hot-spots on Smad3 will have
      distinct consequences on Smad3-mediated responses. METHODOLOGY/PRINCIPAL
      FINDINGS: We mutated 28 amino acids on the surface of the Smad3 MH2 domain and
      identified 22 Smad3 variants with reduced binding to subsets of 17 Smad3-binding
      proteins including Smad4, SARA, Ski, Smurf2 and SIP1. Mutations defective in
      binding to Smad4, e.g., D408H, or defective in nucleocytoplasmic shuttling, e.g.,
      W406A, were compromised in modulating the expression levels of a Smad3-dependent
      reporter gene or six endogenous Smad3-responsive genes: Mmp9, IL11, Tnfaip6,
      Fermt1, Olfm2 and Wnt11. However, the Smad3 mutants Y226A, Y297A, W326A, K341A,
      and E267A had distinct differences on TGF-beta signaling. For example, K341A and
      Y226A both reduced the Smad3-mediated activation of the reporter gene by ~50% but
      K341A only reduced the TGF-beta inducibilty of Olfm2 in contrast to Y226A which
      reduced the TGF-beta inducibility of all six endogenous genes as severely as the
      W406A mutation. E267A had increased protein binding but reduced TGF-beta
      inducibility because it caused higher basal levels of expression. Y297A had
      increased TGF-beta inducibility because it caused lower Smad3-induced basal
      levels of gene expression. CONCLUSIONS/SIGNIFICANCE: Mutations in protein binding
      hot-spots on Smad3 reduced the binding to different subsets of interacting
      proteins and caused a range of quantitative changes in the expression of genes
      induced by Smad3. This approach should be useful for unraveling which Smad3
      protein complexes are critical for specific biological responses.

PMID- 21949840
TI  - Anti-nucleocapsid protein immune responses counteract pathogenic effects of Rift
      Valley fever virus infection in mice.
AB  - The known virulence factor of Rift Valley fever virus (RVFV), the NSs protein,
      counteracts the antiviral effects of the type I interferon response. In this
      study we evaluated the expression of several genes in the liver and spleen
      involved in innate and adaptive immunity of mice immunized with a RVFV
      recombinant nucleocapsid protein (recNP) combined with Alhydrogel adjuvant and
      control animals after challenge with wild type RVFV. Mice immunized with recNP
      elicited an earlier IFNbeta response after challenge compared to non-immunized
      controls. In the acute phase of liver infection in non-immunized mice there was a
      massive upregulation of type I and II interferon, accompanied by high viral
      titers, and the up- and downregulation of several genes involved in the
      activation of B- and T-cells, indicating that both humoral and cellular immunity
      is modulated during RVFV infection. Various genes involved in pro-inflammatory
      responses and with pro-apoptotic effects were strongly upregulated and anti
      apoptotic genes were downregulated in liver of non-immunized mice. Expression of
      many genes involved in B- and T-cell immunity were downregulated in spleen of non
      immunized mice but normal in immunized mice. A strong bias towards apoptosis and
      inflammation in non-immunized mice at an acute stage of liver infection
      associated with suppression of several genes involved in activation of humoral
      and cellular immunity in spleen, suggests that RVFV evades the host immune
      response in more ways than only by inhibition of type I interferon, and that
      immunopathology of the liver plays a crucial role in RVF disease progression.

PMID- 21949841
TI  - Arginine cofactors on the polymerase ribozyme.
AB  - The RNA world hypothesis states that the early evolution of life went through a
      stage in which RNA served both as genome and as catalyst. The central catalyst in
      an RNA world organism would have been a ribozyme that catalyzed RNA
      polymerization to facilitate self-replication. An RNA polymerase ribozyme was
      developed previously in the lab but it is not efficient enough for self
      replication. The factor that limits its polymerization efficiency is its weak
      sequence-independent binding of the primer/template substrate. Here we tested
      whether RNA polymerization could be improved by a cationic arginine cofactor, to
      improve the interaction with the substrate. In an RNA world, amino acid-nucleic
      acid conjugates could have facilitated the emergence of the translation apparatus
      and the transition to an RNP world. We chose the amino acid arginine for our
      study because this is the amino acid most adept to interact with RNA. An arginine
      cofactor was positioned at ten different sites on the ribozyme, using conjugates
      of arginine with short DNA or RNA oligonucleotides. However, polymerization
      efficiency was not increased in any of the ten positions. In five of the ten
      positions the arginine reduced or modulated polymerization efficiency, which
      gives insight into the substrate-binding site on the ribozyme. These results
      suggest that the existing polymerase ribozyme is not well suited to using an
      arginine cofactor.

PMID- 21949842
TI  - REST: a toolkit for resting-state functional magnetic resonance imaging data
      processing.
AB  - Resting-state fMRI (RS-fMRI) has been drawing more and more attention in recent
      years. However, a publicly available, systematically integrated and easy-to-use
      tool for RS-fMRI data processing is still lacking. We developed a toolkit for the
      analysis of RS-fMRI data, namely the RESting-state fMRI data analysis Toolkit
      (REST). REST was developed in MATLAB with graphical user interface (GUI). After
      data preprocessing with SPM or AFNI, a few analytic methods can be performed in
      REST, including functional connectivity analysis based on linear correlation,
      regional homogeneity, amplitude of low frequency fluctuation (ALFF), and
      fractional ALFF. A few additional functions were implemented in REST, including a
      DICOM sorter, linear trend removal, bandpass filtering, time course extraction,
      regression of covariates, image calculator, statistical analysis, and slice
      viewer (for result visualization, multiple comparison correction, etc.). REST is
      an open-source package and is freely available at http://www.restfmri.net.

PMID- 21949843
TI  - Astrocyte-derived tissue transglutaminase interacts with fibronectin: a role in
      astrocyte adhesion and migration?
AB  - An important neuropathological feature of neuroinflammatory processes that occur
      during e.g. Multiple Sclerosis (MS) is the formation of an astroglial scar.
      Astroglial scar formation is facilitated by the interaction between astrocytes
      and extracellular matrix proteins (ECM) such as fibronectin. Since there is
      evidence indicating that glial scars strongly inhibit both axon growth and
      (re)myelination in brain lesions, it is important to understand the factors that
      contribute to the interaction between astrocytes and ECM proteins. Tissue
      Transglutaminase (TG2) is a multifunctional enzyme with an ubiquitous tissue
      distribution, being clearly present within the brain. It has been shown that
      inflammatory cytokines can enhance TG2 activity. In addition, TG2 can mediate
      cell adhesion and migration and it binds fibronectin with high affinity. We
      therefore hypothesized that TG2 is involved in astrocyte-fibronectin
      interactions. Our studies using primary rat astrocytes show that intracellular
      and cell surface expression and activity of TG2 is increased after treatment with
      pro-inflammatory cytokines. Astrocyte-derived TG2 interacts with fibronectin and
      is involved in astrocyte adhesion onto and migration across fibronectin. TG2 is
      involved in stimulating focal adhesion formation which is necessary for the
      interaction of astrocytes with ECM proteins. We conclude that astrocyte-derived
      TG2 contributes to the interaction between astrocytes and fibronectin. It might
      thereby regulate ECM remodeling and possibly glial scarring.

PMID- 21949844
TI  - 11beta-Hydroxysteroid dehydrogenase-1 is a novel regulator of skin homeostasis
      and a candidate target for promoting tissue repair.
AB  - 11beta-Hydroxysteroid dehydrogenase 1 (11beta-HSD1) catalyzes the interconversion
      of cortisone and cortisol within the endoplasmic reticulum. 11beta-HSD1 is
      expressed widely, most notably in the liver, adipose tissue, and central nervous
      system. It has been studied intensely over the last 10 years because its activity
      is reported to be increased in visceral adipose tissue of obese people. Epidermal
      keratinocytes and dermal fibroblasts also express 11beta-HSD1. However, the
      function of the enzymatic activity 11beta-HSD1 in skin is not known. We found
      that 11beta-HSD1 was expressed in human and murine epidermis, and this expression
      increased as keratinocytes differentiate. The expression of 11beta-HSD1 by normal
      human epidermal keratinocytes (NHEKs) was increased by starvation or calcium
      induced differentiation in vitro. A selective inhibitor of 11beta-HSD1 promoted
      proliferation of NHEKs and normal human dermal fibroblasts, but did not alter the
      differentiation of NHEKs. Topical application of selective 11beta-HSD1 inhibitor
      to the dorsal skin of hairless mice caused proliferation of keratinocytes. Taken
      together, these data suggest that 11beta-HSD1 is involved in tissue remodeling of
      the skin. This hypothesis was further supported by the observation that topical
      application of the selective 11beta-HSD1 inhibitor enhanced cutaneous wound
      healing in C57BL/6 mice and ob/ob mice. Collectively, we conclude that 11beta
      HSD1 is negatively regulating the proliferation of keratinocytes and fibroblasts,
      and cutaneous wound healing. Hence, 11beta-HSD1 might maintain skin homeostasis
      by regulating the proliferation of keratinocytes and dermal fibroblasts. Thus
      11beta-HSD1 is a novel candidate target for the design of skin disease
      treatments.

PMID- 21949845
TI  - ZMIZ1 preferably enhances the transcriptional activity of androgen receptor with
      short polyglutamine tract.
AB  - The androgen receptor (AR) is a ligand-induced transcription factor and contains
      the polyglutamine (polyQ) tracts within its N-terminal transactivation domain.
      The length of polyQ tracts has been suggested to alter AR transcriptional
      activity in prostate cancer along with other endocrine and neurologic disorders.
      Here, we assessed the role of ZMIZ1, an AR co-activator, in regulating the
      activity of the AR with different lengths of polyQ tracts as ARQ9, ARQ24, and
      ARQ35 in prostate cancer cells. ZMIZ1, but not ZMIZ2 or ARA70, preferably
      augments ARQ9 induced androgen-dependent transcription on three different
      androgen-inducible promoter/reporter vectors. A strong protein-protein
      interaction between ZMIZ1 and ARQ9 proteins was shown by immunoprecipitation
      assays. In the presence of ZMIZ1, the N and C-terminal interaction of the ARQ9
      was more pronounced than ARQ24 and ARQ35. Both Brg1 and BAF57, the components of
      SWI/SNF complexes, were shown to be involved in the enhancement of ZMIZ1 on AR
      activity. Using the chromatin immunoprecipitation assays (ChIP), we further
      demonstrated a strong recruitment of ZMIZ1 by ARQ9 on the promoter of the
      prostate specific antigen (PSA) gene. These results demonstrate a novel
      regulatory role of ZMIZ1 in modulating the polyQ tract length of AR in prostate
      cancer cells.

PMID- 21949846
TI  - Protective role of heme oxygenase-1 in Listeria monocytogenes-induced abortion.
AB  - It is well-known fact that various pathogens, including bacteria, virus, and
      protozoa, induce abortion in humans and animals. However the mechanisms of
      infectious abortion are little known. In this study, we demonstrated that
      Listeria monocytogenes infection in trophoblast giant cells decreased heme
      oxygenase (HO)-1 and B-cell lymphoma-extra large (Bcl-XL) expression, and that
      their overexpression inhibited cell death induced by the infection. Furthermore,
      HO-1 and Bcl-XL expression levels were also decreased by L. monocytogenes in
      pregnant mice. Treatment with cobalt protoporphyrin, which is known to induce HO
      1, inhibited infectious abortion. Taken together, our study indicates that L.
      monocytogenes infection decreases HO-1 and Bcl-XL expression and induces cell
      death in placenta, leading to infectious abortion.

PMID- 21949847
TI  - Diverse arrangement of photosynthetic gene clusters in aerobic anoxygenic
      phototrophic bacteria.
AB  - BACKGROUND: Aerobic anoxygenic photototrophic (AAP) bacteria represent an
      important group of marine microorganisms inhabiting the euphotic zone of the
      ocean. They harvest light using bacteriochlorophyll (BChl) a and are thought to
      be important players in carbon cycling in the ocean. METHODOLOGY/PRINCIPAL
      FINDINGS: Aerobic anoxygenic phototrophic (AAP) bacteria represent an important
      part of marine microbial communities. Their photosynthetic apparatus is encoded
      by a number of genes organized in a so-called photosynthetic gene cluster (PGC).
      In this study, the organization of PGCs was analyzed in ten AAP species belonging
      to the orders Rhodobacterales, Sphingomonadales and the NOR5/OM60 clade.
      Sphingomonadales contained comparatively smaller PGCs with an approximately size
      of 39 kb whereas the average size of PGCs in Rhodobacterales and NOR5/OM60 clade
      was about 45 kb. The distribution of four arrangements, based on the permutation
      and combination of the two conserved regions bchFNBHLM-LhaA-puhABC and crtF
      bchCXYZ, does not correspond to the phylogenetic affiliation of individual AAP
      bacterial species. While PGCs of all analyzed species contained the same set of
      genes for bacteriochlorophyll synthesis and assembly of photosynthetic centers,
      they differed largely in the carotenoid biosynthetic genes. Spheroidenone,
      spirilloxanthin, and zeaxanthin biosynthetic pathways were found in each clade
      respectively. All of the carotenoid biosynthetic genes were found in the PGCs of
      Rhodobacterales, however Sphingomonadales and NOR5/OM60 strains contained some of
      the carotenoid biosynthetic pathway genes outside of the PGC.
      CONCLUSIONS/SIGNIFICANCE: Our investigations shed light on the evolution and
      functional implications in PGCs of marine aerobic anoxygenic phototrophs, and
      support the notion that AAP are a heterogenous physiological group
      phylogenetically scattered among Proteobacteria.

PMID- 21949848
TI  - Tumor necrosis factor-alpha and Muc2 mucin play major roles in disease onset and
      progression in dextran sodium sulphate-induced colitis.
AB  - The sequential events and the inflammatory mediators that characterize disease
      onset and progression of ulcerative colitis (UC) are not well known. In this
      study, we evaluated the early pathologic events in the pathogenesis of colonic
      ulcers in rats treated with dextran sodium sulfate (DSS). Following a lag phase,
      day 5 of DSS treatment was found clinically most critical as disease activity
      index (DAI) exhibited an exponential rise with severe weight loss and rectal
      bleeding. Surprisingly, on days 1-2, colonic TNF-alpha expression (70-80-fold)
      and tissue protein (50-fold) were increased, whereas IL-1beta only increased on
      days 7-9 (60-90-fold). Days 3-6 of DSS treatment were characterized by a
      prominent down regulation in the expression of regulatory cytokines (40-fold for
      IL-10 and TGFbeta) and mucin genes (15-18 fold for Muc2 and Muc3) concomitant
      with depletion of goblet cell and adherent mucin. Remarkably, treatment with TNF
      alpha neutralizing antibody markedly altered DSS injury with reduced DAI,
      restoration of the adherent and goblet cell mucin and IL-1beta and mucin gene
      expression. We conclude that early onset colitis is dependent on TNF-alpha that
      preceded depletion of adherent and goblet cell mucin prior to epithelial cell
      damage and these biomarkers can be used as therapeutic targets for UC.

PMID- 21949849
TI  - Homozygosity mapping on homozygosity haplotype analysis to detect recessive
      disease-causing genes from a small number of unrelated, outbred patients.
AB  - Genes involved in disease that are not common are often difficult to identify; a
      method that pinpoints them from a small number of unrelated patients will be of
      great help. In order to establish such a method that detects recessive genes
      identical-by-descent, we modified homozygosity mapping (HM) so that it is
      constructed on the basis of homozygosity haplotype (HM on HH) analysis. An
      analysis using 6 unrelated patients with Siiyama-type alpha1-antitrypsin
      deficiency, a disease caused by a founder gene, the correct gene locus was
      pinpointed from data of any 2 patients (length: 1.2-21.8 centimorgans, median:
      1.6 centimorgans). For a test population in which these 6 patients and 54 healthy
      subjects were scrambled, the approach accurately identified these 6 patients and
      pinpointed the locus to a 1.4-centimorgan fragment. Analyses using synthetic data
      revealed that the analysis works well for IBD fragment derived from a most recent
      common ancestor (MRCA) who existed less than 60 generations ago. The analysis is
      unsuitable for the genes with a frequency in general population more than 0.1.
      Thus, HM on HH analysis is a powerful technique, applicable to a small number of
      patients not known to be related, and will accelerate the identification of
      disease-causing genes for recessive conditions.

PMID- 21949850
TI  - The tissue-specific Rep8/UBXD6 tethers p97 to the endoplasmic reticulum membrane
      for degradation of misfolded proteins.
AB  - The protein known as p97 or VCP in mammals and Cdc48 in yeast is a versatile
      ATPase complex involved in several biological functions including membrane
      fusion, protein folding, and activation of membrane-bound transcription factors.
      In addition, p97 plays a central role in degradation of misfolded secretory
      proteins via the ER-associated degradation pathway. This functional diversity of
      p97 depends on its association with various cofactors, and to further our
      understanding of p97 function it is important that these cofactors are identified
      and analyzed. Here, we isolate and characterize the human protein named Rep8 or
      Ubxd6 as a new cofactor of p97. Mouse Rep8 is highly tissue-specific and abundant
      in gonads. In testes, Rep8 is expressed in post-meiotic round spermatids, whereas
      in ovaries Rep8 is expressed in granulosa cells. Rep8 associates directly with
      p97 via its UBX domain. We show that Rep8 is a transmembrane protein that
      localizes to the ER membrane with its UBX domain facing the cytoplasm. Knock-down
      of Rep8 expression in human cells leads to a decreased association of p97 with
      the ER membrane and concomitantly a retarded degradation of misfolded ER-derived
      proteasome substrates. Thus, Rep8 tethers p97 to the ER membrane for efficient ER
      associated degradation.

PMID- 21949851
TI  - TGFBR2 and BAX mononucleotide tract mutations, microsatellite instability, and
      prognosis in 1072 colorectal cancers.
AB  - BACKGROUND: Mononucleotide tracts in the coding regions of the TGFBR2 and BAX
      genes are commonly mutated in microsatellite instability-high (MSI-high) colon
      cancers. The receptor TGFBR2 plays an important role in the TGFB1 (transforming
      growth factor-beta, TGF-beta) signaling pathway, and BAX plays a key role in
      apoptosis. However, a role of TGFBR2 or BAX mononucleotide mutation in colorectal
      cancer as a prognostic biomarker remains uncertain. METHODOLOGY/PRINCIPAL
      FINDINGS: We utilized a database of 1072 rectal and colon cancers in two
      prospective cohort studies (the Nurses' Health Study and the Health Professionals
      Follow-up Study). Cox proportional hazards model was used to compute mortality
      hazard ratio (HR), adjusted for clinical, pathological and molecular features
      including the CpG island methylator phenotype (CIMP), LINE-1 methylation, and
      KRAS, BRAF and PIK3CA mutations. MSI-high was observed in 15% (162/1072) of all
      colorectal cancers. TGFBR2 and BAX mononucleotide mutations were detected in 74%
      (117/159) and 30% (48/158) of MSI-high tumors, respectively. In Kaplan-Meier
      analysis as well as univariate and multivariate Cox regression analyses, compared
      to microsatellite stable (MSS)/MSI-low cases, MSI-high cases were associated with
      superior colorectal cancer-specific survival [adjusted HR, 0.34; 95% confidence
      interval (CI), 0.20-0.57] regardless of TGFBR2 or BAX mutation status. Among MSI
      high tumors, TGFBR2 mononucleotide mutation was associated with CIMP-high
      independent of other variables [multivariate odds ratio, 3.57; 95% CI, 1.66-7.66;
      p = 0.0011]. CONCLUSIONS: TGFBR2 or BAX mononucleotide mutations are not
      associated with the patient survival outcome in MSI-high colorectal cancer. Our
      data do not support those mutations as prognostic biomarkers (beyond MSI) in
      colorectal carcinoma.

PMID- 21949852
TI  - Expression of signal transduction system encoding genes of Yersinia
      pseudotuberculosis IP32953 at 28 degrees C and 3 degrees C.
AB  - Yersinia pseudotuberculosis is a significant psychrotrophic food pathogen whose
      cold tolerance mechanisms are poorly understood. Signal transduction systems
      serve to monitor the environment, but no systematic investigation of their role
      at cold temperatures in Y. pseudotuberculosis has yet been undertaken. The
      relative expression levels of 54 genes predicted to encode proteins belonging to
      signal transduction systems in Y. pseudotuberculosis IP32953 were determined at
      28 degrees C and 3 degrees C by quantitative real-time reverse transcription-PCR.
      The relative expression levels of 44 genes were significantly (p<0.05) higher at
      3 degrees C than at 28 degrees C. Genes encoding the two-component system
      CheA/CheY had the highest relative expression levels at 3 degrees C. Mutational
      analysis revealed that cheA is important for growth and motility at 3 degrees C.
      The relative expression level of one gene, rssB, encoding an RpoS regulator, was
      significantly (p<0.05) lower at 3 degrees C than at 28 degrees C. The results
      suggest that several signal transduction systems might be used during growth at
      low temperature, and at least, CheA/CheY two-component system is important for
      low-temperature growth.

PMID- 21949853
TI  - Receptor-mediated endocytosis of alpha-galactosidase A in human podocytes in
      Fabry disease.
AB  - Injury to the glomerular podocyte is a key mechanism in human glomerular disease
      and podocyte repair is an important therapeutic target. In Fabry disease,
      podocyte injury is caused by the intracellular accumulation of
      globotriaosylceramide. This study identifies in the human podocyte three
      endocytic receptors, mannose 6-phosphate/insulin-like growth II receptor,
      megalin, and sortilin and demonstrates their drug delivery capabilities for
      enzyme replacement therapy. Sortilin, a novel alpha-galactosidase A binding
      protein, reveals a predominant intracellular expression but also surface
      expression in the podocyte. The present study provides the rationale for the
      renal effect of treatment with alpha-galactosidase A and identifies potential
      pathways for future non-carbohydrate based drug delivery to the kidney podocyte
      and other potential affected organs.

PMID- 21949854
TI  - Phenotype enhancement screen of a regulatory spx mutant unveils a role for the
      ytpQ gene in the control of iron homeostasis.
AB  - Spx is a global regulator of genes that are induced by disulfide stress in
      Bacillus subtilis. The regulon that it governs is comprised of over 120 genes
      based on microarray analysis, although it is not known how many of these are
      under direct Spx control. Most of the Spx-regulated genes (SRGs) are of unknown
      function, but many encode products that are conserved in low %GC Gram-positive
      bacteria. Using a gene-disruption library of B. subtilis genomic mutations, the
      SRGs were screened for phenotypes related to Spx-controlled activities, such as
      poor growth in minimal medium and sensitivity to methyglyoxal, but nearly all of
      the SRG mutations showed little if any phenotype. To uncover SRG function, the
      mutations were rescreened in an spx mutant background to determine which mutant
      SRG allele would enhance the spx mutant phenotype. One of the SRGs, ytpQ was the
      site of a mutation that, when combined with an spx null mutation, elevated the
      severity of the Spx mutant phenotype, as shown by reduced growth in a minimal
      medium and by hypersensitivity to methyglyoxal. The ytpQ mutant showed elevated
      oxidative protein damage when exposed to methylglyoxal, and reduced growth rate
      in liquid culture. Proteomic and transcriptomic data indicated that the ytpQ
      mutation caused the derepression of the Fur and PerR regulons of B. subtilis. Our
      study suggests that the ytpQ gene, encoding a conserved DUF1444 protein,
      functions directly or indirectly in iron homeostasis. The ytpQ mutant phenotype
      mimics that of a fur mutation, suggesting a condition of low cellular iron. In
      vitro transcription analysis indicated that Spx stimulates transcription from the
      ytpPQR operon within which the ytpQ gene resides. The work uncovers a link
      between Spx and control of iron homeostasis.

PMID- 21949855
TI  - Circadian cycles of gene expression in the coral, Acropora millepora.
AB  - BACKGROUND: Circadian rhythms regulate many physiological, behavioral and
      reproductive processes. These rhythms are often controlled by light, and daily
      cycles of solar illumination entrain many clock regulated processes. In
      scleractinian corals a number of different processes and behaviors are associated
      with specific periods of solar illumination or non-illumination--for example,
      skeletal deposition, feeding and both brooding and broadcast spawning.
      METHODOLOGY/PRINCIPAL FINDINGS: We have undertaken an analysis of diurnal
      expression of the whole transcriptome and more focused studies on a number of
      candidate circadian genes in the coral Acropora millepora using deep RNA
      sequencing and quantitative PCR. Many examples of diurnal cycles of RNA abundance
      were identified, some of which are light responsive and damped quickly under
      constant darkness, for example, cryptochrome 1 and timeless, but others that
      continue to cycle in a robust manner when kept in constant darkness, for example,
      clock, cryptochrome 2, cycle and eyes absent, indicating that their transcription
      is regulated by an endogenous clock entrained to the light-dark cycle. Many other
      biological processes that varied between day and night were also identified by a
      clustering analysis of gene ontology annotations. CONCLUSIONS/SIGNIFICANCE:
      Corals exhibit diurnal patterns of gene expression that may participate in the
      regulation of circadian biological processes. Rhythmic cycles of gene expression
      occur under constant darkness in both populations of coral larvae that lack
      zooxanthellae and in individual adult tissue containing zooxanthellae, indicating
      that transcription is under the control of a biological clock. In addition to
      genes potentially involved in regulating circadian processes, many other pathways
      were found to display diel cycles of transcription.

PMID- 21949856
TI  - Reduced transmissibility of East African Indian strains of Mycobacterium
      tuberculosis.
AB  - BACKGROUND: Mycobacterium tuberculosis (MTB) has been classified into 4 main
      lineages. Some reports have associated certain lineages with particular clinical
      phenotypes, but there is still insufficient information regarding the clinical
      and epidemiologic implications of MTB lineage variation. METHODS: Using large
      sequence polymorphisms we classified MTB isolates from a population-based study
      in Montreal, Canada into the 4 major lineages, and identified the associated
      clinical and epidemiologic features. In addition, IS6110-RFLP and spoligotyping
      were used as indicators of recent TB transmission. The study population was
      divided into a derivation cohort, diagnosed between 2001 and 2007, and a separate
      validation cohort, diagnosed between 1996 and 2000. RESULTS: In the derivation
      cohort, when compared to the other MTB lineages, the East African-Indian (EAI)
      lineage was associated with lower rates of TB transmission, as measured by:
      positive TST among close contacts of pulmonary TB cases (adjusted odds ratio 0.6:
      [95% confidence interval 0.4-0.9]), and clustered TB cases (0.3: [<0.001-0.6]).
      Severe forms of TB were also less likely among the EAI group (0.4: [<0.001-0.8]).
      There were no significant differences when comparing patients with the other MTB
      lineages. In the validation cohort, the EAI lineage was associated with lower
      rates of positive TST among contacts (0.5: [0.3-0.9]) and a trend towards less
      clustered TB cases (0.5: [0.1-1.8]) when compared to the other lineages. Disease
      severity among the different groups was not significantly different in the
      validation cohort. CONCLUSIONS: We conclude that in Montreal, EAI strains were
      associated with reduced transmission compared to other MTB lineages.

PMID- 21949857
TI  - Orexin neurons receive glycinergic innervations.
AB  - Glycine, a nonessential amino-acid that acts as an inhibitory neurotransmitter in
      the central nervous system, is currently used as a dietary supplement to improve
      the quality of sleep, but its mechanism of action is poorly understood. We
      confirmed the effects of glycine on sleep/wakefulness behavior in mice when
      administered peripherally. Glycine administration increased non-rapid eye
      movement (NREM) sleep time and decreased the amount and mean episode duration of
      wakefulness when administered in the dark period. Since peripheral administration
      of glycine induced fragmentation of sleep/wakefulness states, which is a
      characteristic of orexin deficiency, we examined the effects of glycine on orexin
      neurons. The number of Fos-positive orexin neurons markedly decreased after
      intraperitoneal administration of glycine to mice. To examine whether glycine
      acts directly on orexin neurons, we examined the effects of glycine on orexin
      neurons by patch-clamp electrophysiology. Glycine directly induced
      hyperpolarization and cessation of firing of orexin neurons. These responses were
      inhibited by a specific glycine receptor antagonist, strychnine. Triple-labeling
      immunofluorescent analysis showed close apposition of glycine transporter 2
      (GlyT2)-immunoreactive glycinergic fibers onto orexin-immunoreactive neurons.
      Immunoelectron microscopic analysis revealed that GlyT2-immunoreactive terminals
      made symmetrical synaptic contacts with somata and dendrites of orexin neurons.
      Double-labeling immunoelectron microscopy demonstrated that glycine receptor
      alpha subunits were localized in the postsynaptic membrane of symmetrical
      inhibitory synapses on orexin neurons. Considering the importance of glycinergic
      regulation during REM sleep, our observations suggest that glycine injection
      might affect the activity of orexin neurons, and that glycinergic inhibition of
      orexin neurons might play a role in physiological sleep regulation.

PMID- 21949859
TI  - Rhythmic leptin is required for weight gain from circadian desynchronized feeding
      in the mouse.
AB  - The neuroendocrine and metabolic effects of leptin have been extensively
      researched since the discovery, and the later identification, of the leptin gene
      mutated within the ob/ob mouse. Leptin is required for optimal health in a number
      of physiological systems (e.g. fertility, bone density, body weight regulation).
      Despite the extensive leptin literature and many observations of leptin's
      cyclical pattern over the 24-hour day, few studies have specifically examined how
      the circadian rhythm of leptin may be essential to leptin signaling and health.
      Here we present data indicating that a rhythmic leptin profile (e.g. 1 peak every
      24 hours) leads to excessive weight gain during desynchronized feeding whereas
      non-rhythmic leptin provided in a continuous manner does not lead to excessive
      body weight gain under similar feeding conditions. This study suggests that
      feeding time can interact with leptin's endogenous rhythm to influence metabolic
      signals, specifically leading to excessive body weight gains during 'wrongly'
      timed feeding.

PMID- 21949858
TI  - Ceruloplasmin deficiency reduces levels of iron and BDNF in the cortex and
      striatum of young mice and increases their vulnerability to stroke.
AB  - Ceruloplasmin (Cp) is an essential ferroxidase that plays important roles in
      cellular iron trafficking. Previous findings suggest that the proper regulation
      and subcellular localization of iron are very important in brain cell function
      and viability. Brain iron dyshomeostasis is observed during normal aging, as well
      as in several neurodegenerative disorders such as Alzheimer's, Parkinson's and
      Huntington's diseases, coincident with areas more susceptible to insults. Because
      of their high metabolic demand and electrical excitability, neurons are
      particularly vulnerable to ischemic injury and death. We therefore set out to
      look for abnormalities in the brain of young adult mice that lack Cp. We found
      that iron levels in the striatum and cerebral cortex of these young animals are
      significantly lower than wild-type (WT) controls. Also mRNA levels of the
      neurotrophin brain derived neurotrophic factor (BDNF), known for its role in
      maintenance of cell viability, were decreased in these brain areas. Chelator
      mediated depletion of iron in cultured neural cells resulted in reduced BDNF
      expression by a posttranscriptional mechanism, suggesting a causal link between
      low brain iron levels and reduced BDNF expression. When the mice were subjected
      to middle cerebral artery occlusion, a model of focal ischemic stroke, we found
      increased brain damage in Cp-deficient mice compared to WT controls. Our data
      indicate that lack of Cp increases neuronal susceptibility to ischemic injury by
      a mechanism that may involve reduced levels of iron and BDNF.

PMID- 21949860
TI  - The complex vaginal flora of West African women with bacterial vaginosis.
AB  - BACKGROUND: The spectrum of bacteria associated with bacterial vaginosis (BV) has
      recently expanded through taxonomic changes and the use of molecular methods.
      These methods have yet to be used in large-scale epidemiological studies in
      Africa where BV is highly prevalent. METHODS: An analysis of samples obtained
      during a clinical trial of the management of vaginal discharge in four West
      African countries. Samples were available from 1555 participants; 843 (54%) had
      BV. Nucleic acids of 13 bacterial genera or species potentially associated with
      BV were detected through the polymerase chain reaction. RESULTS: The associations
      between various components of the vaginal flora were complex. Excluding
      Lactobacillus, the other 12 micro-organisms were all associated with each other
      at the p<=0.001 level. The prevalence of various bacterial genera or species
      varied according to age, sexual activity and HIV status. In multivariate
      analysis, the presence of Gardnerella vaginalis, Bifidobacterium, Megasphaera
      elsdenii, Dialister, Mycoplasma hominis, Leptotrichia, and Prevotella were
      independently associated with BV as was the absence of Lactobacillus and
      Peptoniphilus. However, Mobiluncus, Atopobium vaginae, Anaerococcus, and
      Eggerthella were not independently associated with BV. Unexpectedly, after
      treatment with a regimen that included either metronidazole or tinidazole, the
      proportion of patients with a complete resolution of symptoms by day 14 increased
      with the number of bacterial genera or species present at enrolment. CONCLUSIONS:
      Numerous bacterial genera or species were strongly associated with each other in
      a pattern that suggested a symbiotic relationship. BV cases with a simpler flora
      were less likely to respond to treatment. Overall, the vaginal flora of West
      African women with BV was reminiscent of that of their counterparts in
      industrialized countries.

PMID- 21949861
TI  - Nucleoporin98-96 function is required for transit amplification divisions in the
      germ line of Drosophila melanogaster.
AB  - Production of specialized cells from precursors depends on a tightly regulated
      sequence of proliferation and differentiation steps. In the gonad of Drosophila
      melanogaster, the daughters of germ line stem cells (GSC) go through precisely
      four rounds of transit amplification divisions to produce clusters of 16
      interconnected germ line cells before entering a stereotypic differentiation
      cascade. Here we show that animals harbouring a transposon insertion in the
      center of the complex nucleoporin98-96 (nup98-96) locus had severe defects in the
      early steps of this developmental program, ultimately leading to germ cell loss
      and sterility. A phenotypic analysis indicated that flies carrying the transposon
      insertion, designated nup98-96(2288), had dramatically reduced numbers of germ
      line cells. In contrast to controls, mutant testes contained many solitary germ
      line cells that had committed to differentiation as well as abnormally small
      clusters of two, four or eight differentiating germ line cells. This indicates
      that mutant GSCs rather differentiated than self-renewed, and that these GSCs and
      their daughters initiated the differentiation cascade after zero, or less than
      four rounds of amplification divisions. This phenotype remained unaffected by
      hyper-activation of signalling pathways that normally result in excessive
      proliferation of GSCs and their daughters. Expression of wildtype nup98-96
      specifically in the germ line cells of mutant animals fully restored development
      of the GSC lineage, demonstrating that the effect of the mutation is cell
      autonomous. Nucleoporins are the structural components of the nucleopore and have
      also been implicated in transcriptional regulation of specific target genes. The
      nuclear envelopes of germ cells and general nucleocytoplasmic transport in nup98
      96 mutant animals appeared normal, leading us to propose that Drosophila nup98-96
      mediates the transport or transcription of targets required for the developmental
      timing between amplification and differentiation.

PMID- 21949862
TI  - The soluble recombinant Neisseria meningitidis adhesin NadA(Delta351-405)
      stimulates human monocytes by binding to extracellular Hsp90.
AB  - The adhesin NadA favors cell adhesion/invasion by hypervirulent Neisseria
      meningitidis B (MenB). Its recombinant form NadA(Delta351-405,) devoid of the
      outer membrane domain, is an immunogenic candidate for an anti-MenB vaccine able
      to stimulate monocytes, macrophages and dendritic cells. In this study we
      investigated the molecular mechanism of NadA(Delta351-405) cellular effects in
      monocytes. We show that NadA(Delta351-405) (against which we obtained polyclonal
      antibodies in rabbits), binds to hsp90, but not to other extracellular homologous
      heat shock proteins grp94 and hsp70, in vitro and on the surface of monocytes, in
      a temperature dependent way. Pre-incubation of monocytes with the MenB soluble
      adhesin interfered with the binding of anti-hsp90 and anti-hsp70 antibodies to
      hsp90 and hsp70 at 37 degrees C, a condition in which specific cell-binding
      occurs, but not at 0 degrees C, a condition in which specific cell-binding is
      very diminished. Conversely, pre-incubation of monocytes with anti-hsp90 and anti
      hsp70 antibodies did not affected NadA(Delta351-405) cell binding in any
      temperature condition, indicating that it associates to another receptor on their
      plasma membrane and then laterally diffuses to encounter hsp90. Consistently,
      polymixin B interfered with NadA(Delta351-405) /hsp90 association, abrogated the
      decrease of anti-hsp90 antibodies binding to the cell surface due to
      NadA(Delta351-405) and inhibited adhesin-induced cytokine/chemokine secretion
      without affecting monocyte-adhesin binding. Co-stimulation of monocytes with anti
      hsp90 antibodies and NadA(Delta351-405) determined a stronger but polymixin B
      insensitive cell activation. This indicated that the formation of a recombinant
      NadA/hsp90/hsp70 complex, although essential for full monocyte stimulation, can
      be replaced by anti-hsp90 antibody/hsp90 binding. Finally, the activation of
      monocytes by NadA(Delta351-405) alone or in the presence of anti-hsp90 antibodies
      were both inhibited by neutralizing anti-TLR4 antibodies, but not by anti-TLR2
      antibodies. We propose that hsp90-dependent recruitment into an hsp90/hsp70/TLR4
      transducing signal complex is necessary for the immune-stimulating activity of
      NadA(Delta351-405) anti-MenB vaccine candidate.

PMID- 21949863
TI  - Characterization and regulation of the osmolyte betaine synthesizing enzymes GSMT
      and SDMT from halophilic methanogen Methanohalophilus portucalensis.
AB  - The halophilic methanoarchaeon Methanohalophilus portucalensis can synthesize the
      osmolyte betaine de novo in response to extracellular salt stress. Betaine is
      generated by the stepwise methylation of glycine to form sarcosine, N, N
      dimethylglycine and betaine by using S-adenosyl-L-methionine (AdoMet) as the
      methyl donor. The complete gene cluster of Mpgsmt-sdmt was cloned from Southern
      hybridization and heterologous expressed in E. coli respectively. The recombinant
      MpGSMT and MpSDMT both retained their in vivo functional activities in E. coli
      BL21(DE3)RIL to synthesize and accumulate betaine and conferred elevated survival
      ability in betaine transport deficient mutant E. coli MKH13 under high salt
      stress. The dramatic activating effects of sodium and potassium ions on the in
      vitro methyltransferase activities of MpGSMT, but not MpSDMT or bacterial GSMT
      and SDMT, revealed that GSMT from halophilic methanoarchaeon possesses novel
      regulate mechanism in betaine biosynthesis pathway. The circular dichroism
      spectra showed the fluctuated peaks at 206 nm were detected in the MpGSMT under
      various concentrations of potassium or sodium ions. This fluctuated difference
      may cause by a change in the beta-turn structure located at the conserved glycine
      and sarcosine-binding residue Arg167 of MpGSMT. The analytical
      ultracentrifugation analysis indicated that the monomer MpGSMT switched to
      dimeric form increased from 7.6% to 70% with KCl concentration increased from 0
      to 2.0 M. The level of potassium and sodium ions may modulate the substrate
      binding activity of MpGSMT through the conformational change. Additionally,
      MpGSMT showed a strong end product, betaine, inhibitory effect and was more
      sensitive to the inhibitor AdoHcy. The above results indicated that the first
      enzymatic step involved in synthesizing the osmolyte betaine in halophilic
      archaea, namely, GSMT, may also play a major role in coupling the salt-in and
      compatible solute (osmolyte) osmoadaptative strategies in halophilic methanogens
      for adapting to high salt environments.

PMID- 21949864
TI  - Type III Nrg1 back signaling enhances functional TRPV1 along sensory axons
      contributing to basal and inflammatory thermal pain sensation.
AB  - Type III Nrg1, a member of the Nrg1 family of signaling proteins, is expressed in
      sensory neurons, where it can signal in a bi-directional manner via interactions
      with the ErbB family of receptor tyrosine kinases (ErbB RTKs). Type III Nrg1
      signaling as a receptor (Type III Nrg1 back signaling) can acutely activate
      phosphatidylinositol-3-kinase (PtdIns3K) signaling, as well as regulate levels of
      alpha7* nicotinic acetylcholine receptors, along sensory axons. Transient
      receptor potential vanilloid 1 (TRPV1) is a cation-permeable ion channel found in
      primary sensory neurons that is necessary for the detection of thermal pain and
      for the development of thermal hypersensitivity to pain under inflammatory
      conditions. Cell surface expression of TRPV1 can be enhanced by activation of
      PtdIns3K, making it a potential target for regulation by Type III Nrg1. We now
      show that Type III Nrg1 signaling in sensory neurons affects functional axonal
      TRPV1 in a PtdIns3K-dependent manner. Furthermore, mice heterozygous for Type III
      Nrg1 have specific deficits in their ability to respond to noxious thermal
      stimuli and to develop capsaicin-induced thermal hypersensitivity to pain.
      Cumulatively, these results implicate Type III Nrg1 as a novel regulator of TRPV1
      and a molecular mediator of nociceptive function.

PMID- 21949865
TI  - The use of spinning-disk confocal microscopy for the intravital analysis of
      platelet dynamics in response to systemic and local inflammation.
AB  - Platelets are central players in inflammation and are an important component of
      the innate immune response. The ability to visualize platelets within the live
      host is essential to understanding their role in these processes. Past approaches
      have involved adoptive transfer of labelled platelets, non-specific dyes, or the
      use of fluorescent antibodies to tag platelets in vivo. Often, these techniques
      result in either the activation of the platelet, or blockade of specific platelet
      receptors. In this report, we describe two new methods for intravital
      visualization of platelet biology, intravenous administration of labelled anti
      CD49b, which labels all platelets, and CD41-YFP transgenic mice, in which a
      percentage of platelets express YFP. Both approaches label endogenous platelets
      and allow for their visualization using spinning-disk confocal fluorescent
      microscopy. Following LPS-induced inflammation, we were able to measure a
      significant increase in both the number and size of platelet aggregates observed
      within the vasculature of a number of different tissues. Real-time observation of
      these platelet aggregates reveals them to be large, dynamic structures that are
      continually expanding and sloughing-off into circulation. Using these techniques,
      we describe for the first time, platelet recruitment to, and behaviour within
      numerous tissues of the mouse, both under control conditions and following LPS
      induced inflammation.

PMID- 21949866
TI  - Comparative analysis of species-specific ligand recognition in Toll-like receptor
      8 signaling: a hypothesis.
AB  - Toll-like receptors (TLRs) play a central role in the innate immune response by
      recognizing conserved structural patterns in a variety of microbes. TLRs are
      classified into six families, of which TLR7 family members include TLR7, 8, and
      9, which are localized to endolysosomal compartments recognizing viral infection
      in the form of foreign nucleic acids. In our current study, we focused on TLR8,
      which has been shown to recognize different types of ligands such as viral or
      bacterial ssRNA as well as small synthetic molecules. The primary sequences of
      rodent and non-rodent TLR8s are similar, but the antiviral compound (R848) that
      activates the TLR8 pathway is species-specific. Moreover, the factors underlying
      the receptor's species-specificity remain unknown. To this end, comparative
      homology modeling, molecular dynamics simulations refinement, automated docking
      and computational mutagenesis studies were employed to probe the intermolecular
      interactions between this anti-viral compound and TLR8. Furthermore, comparative
      analyses of modeled TLR8 (rodent and non-rodent) structures have shown that the
      variation mainly occurs at LRR14-15 (undefined region); hence, we hypothesized
      that this variation may be the primary reason for the exhibited species
      specificity. Our hypothesis was further bolstered by our docking studies, which
      clearly showed that this undefined region was in close proximity to the ligand
      binding site and thus may play a key role in ligand recognition. In addition, the
      interface between the ligand and TLR8s varied depending upon the amino acid
      charges, free energy of binding, and interaction surface. Therefore, our current
      work provides a hypothesis for previous in vivo studies in the context of TLR
      signaling.

PMID- 21949867
TI  - Colonization-competition tradeoffs as a mechanism driving successional dynamics
      in ectomycorrhizal fungal communities.
AB  - Colonization-competition tradeoffs have been shown to be important determinants
      of succession in plant and animal communities, but their role in ectomycorrhizal
      (ECM) fungal communities is not well understood. To experimentally examine
      whether strong spore-based competitors remain dominant on plant root tips as
      competition shifts to mycelial-based interactions, we investigated the mycelial
      competitive interactions among three naturally co-occurring ECM species
      (Rhizopogon occidentalis, R. salebrosus, and Suillus pungens). Each species was
      grown alone and in all pair-wise combinations on P. muricata seedlings in
      experimental microcosms and culture assays. Competitive outcomes were assessed
      from ECM root tip colonization, soil mycelial abundance, and mycelial growth in
      culture. In the microcosm experiment, we observed a clear competitive hierarchy
      of R. salebrosus>R. occidentalis>S. pungens. Competitive effects were also
      apparent in the culture assays, however, no similar hierarchy was present. These
      results contrast with our previous findings from spore-based competition,
      suggesting that ECM competitive outcomes can be life-stage dependent. The
      differing competitive abilities observed here also showed general correspondence
      with patterns of ECM succession in Pinus muricata forests, indicating that
      competitive interactions may significantly influence temporal patterns of ECM
      community structure.

PMID- 21949868
TI  - Kinetic and sequence-structure-function analysis of known LinA variants with
      different hexachlorocyclohexane isomers.
AB  - BACKGROUND: Here we report specific activities of all seven naturally occurring
      LinA variants towards three different isomers, alpha, gamma and delta, of a
      priority persistent pollutant, hexachlorocyclohexane (HCH). Sequence-structure
      function differences contributing to the differences in their stereospecificity
      for alpha-, gamma-, and delta-HCH and enantiospecificity for (+)- and (-)-alpha 
      HCH are also discussed. METHODOLOGY/PRINCIPAL FINDINGS: Enzyme kinetic studies
      were performed with purified LinA variants. Models of LinA2(B90A) A110T, A111C,
      A110T/A111C and LinA1(B90A) were constructed using the FoldX computer algorithm.
      Turnover rates (min(-1)) showed that the LinAs exhibited differential substrate
      affinity amongst the four HCH isomers tested. alpha-HCH was found to be the most
      preferred substrate by all LinA's, followed by the gamma and then delta isomer.
      CONCLUSIONS/SIGNIFICANCE: The kinetic observations suggest that LinA-gamma1-7 is
      the best variant for developing an enzyme-based bioremediation technology for
      HCH. The majority of the sequence variation in the various linA genes that have
      been isolated is not neutral, but alters the enantio- and stereoselectivity of
      the encoded proteins.

PMID- 21949870
TI  - Optical properties of in situ eye lenses measured with X-ray Talbot
      interferometry: a novel measure of growth processes.
AB  - The lens, a major optical component of the eye, has a gradient refractive index,
      which is required to provide sufficient refractive power and image quality. The
      refractive index variations across the lens are dependent on the distributions
      and concentrations of the varying protein classes. In this study, we present the
      first measurements of the refractive index in the in situ eye lens from five
      species using a specially constructed X-ray Talbot grating interferometer. The
      measurements have been conducted in two planes: the one containing the optic axis
      (the sagittal plane) and the plane orthogonal to this (the equatorial plane). The
      results show previously undetected discontinuities and fluctuations in the
      refractive index profile that vary in different species. These may be linked to
      growth processes and may be the first optical evidence of discrete developmental
      stages.

PMID- 21949869
TI  - Oncogenic stress induced by acute hyper-activation of Bcr-Abl leads to cell death
      upon induction of excessive aerobic glycolysis.
AB  - In response to deregulated oncogene activation, mammalian cells activate disposal
      programs such as programmed cell death. To investigate the mechanisms behind this
      oncogenic stress response we used Bcr-Abl over-expressing cells cultivated in
      presence of imatinib. Imatinib deprivation led to rapid induction of Bcr-Abl
      activity and over-stimulation of PI3K/Akt-, Ras/MAPK-, and JAK/STAT pathways.
      This resulted in a delayed necrosis-like cell death starting not before 48 hours
      after imatinib withdrawal. Cell death was preceded by enhanced glycolysis,
      glutaminolysis, and amino acid metabolism leading to elevated ATP and protein
      levels. This enhanced metabolism could be linked to induction of cell death as
      inhibition of glycolysis or glutaminolysis was sufficient to sustain cell
      viability. Therefore, these data provide first evidence that metabolic changes
      induced by Bcr-Abl hyper-activation are important mediators of oncogenic stress
      induced cell death.During the first 30 hours after imatinib deprivation, Bcr-Abl
      hyper-activation did not affect proliferation but resulted in cellular swelling,
      vacuolization, and induction of eIF2alpha phosphorylation, CHOP expression, as
      well as alternative splicing of XPB, indicating endoplasmic reticulum stress
      response. Cell death was dependent on p38 and RIP1 signaling, whereas classical
      death effectors of ER stress, namely CHOP-BIM were antagonized by concomitant up
      regulation of Bcl-xL.Screening of 1,120 compounds for their potential effects on
      oncogenic stress-induced cell death uncovered that corticosteroids antagonize
      cell death upon Bcr-Abl hyper-activation by normalizing cellular metabolism. This
      protective effect is further demonstrated by the finding that corticosteroids
      rendered lymphocytes permissive to the transforming activity of Bcr-Abl. As
      corticosteroids are used together with imatinib for treatment of Bcr-Abl positive
      acute lymphoblastic leukemia these data could have important implications for the
      design of combination therapy protocols.In conclusion, excessive induction of
      Warburg type metabolic alterations can cause cell death. Our data indicate that
      these metabolic changes are major mediators of oncogenic stress induced by Bcr
      Abl.

PMID- 21949871
TI  - Activin B promotes epithelial wound healing in vivo through RhoA-JNK signaling
      pathway.
AB  - BACKGROUND: Activin B has been reported to promote the proliferation and
      migration of keratinocytes in vitro via the RhoA-JNK signaling pathway, whereas
      its in vivo role and mechanism in wound healing process has not yet been
      elucidated. PRINCIPAL FINDINGS: In this study, we explored the potential
      mechanism by which activin B induces epithelial wound healing in mice.
      Recombinant lentiviral plasmids, with RhoA (N19) and RhoA (L63) were used to
      infect wounded KM mice. The wound healing process was monitored after different
      treatments. Activin B-induced cell proliferation on the wounded skin was
      visualized by electron microscopy and analyzed by 5'-bromodeoxyuridine (BrdU)
      incorporation assay. Protein expression of p-JNK or p-cJun was determined by
      immunohistochemical staining and immunoblotting analysis. Activin B efficiently
      stimulated the proliferation of keratinocytes and hair follicle cells at the
      wound area and promoted wound closure. RhoA positively regulated activin B
      induced wound healing by up-regulating the expression of p-JNK and p-cJun.
      Moreover, suppression of RhoA activation delayed activin B-induced wound healing,
      while JNK inhibition recapitulated phenotypes of RhoA inhibition on wound
      healing. CONCLUSION: These results demonstrate that activin B promotes epithelial
      wound closure in vivo through the RhoA-Rock-JNK-cJun signaling pathway, providing
      novel insight into the essential role of activin B in the therapy of wound
      repair.

PMID- 21949872
TI  - In situ enzyme activity in the dissolved and particulate fraction of the fluid
      from four pitcher plant species of the genus Nepenthes.
AB  - The genus Nepenthes, a carnivorous plant, has a pitcher to trap insects and
      digest them in the contained fluid to gain nutrient. A distinctive character of
      the pitcher fluid is the digestive enzyme activity that may be derived from
      plants and dwelling microbes. However, little is known about in situ digestive
      enzymes in the fluid. Here we examined the pitcher fluid from four species of
      Nepenthes. High bacterial density was observed within the fluids, ranging from
      7*10(6) to 2.2*10(8) cells ml(-1). We measured the activity of three common
      enzymes in the fluid: acid phosphatases, beta-D-glucosidases, and beta-D
      glucosaminidases. All the tested enzymes detected in the liquid of all the
      pitcher species showed activity that considerably exceeded that observed in
      aquatic environments such as freshwater, seawater, and sediment. Our results
      indicate that high enzyme activity within a pitcher could assist in the rapid
      decomposition of prey to maximize efficient nutrient use. In addition, we
      filtered the fluid to distinguish between dissolved enzyme activity and particle
      bound activity. As a result, filtration treatment significantly decreased the
      activity in all enzymes, while pH value and Nepenthes species did not affect the
      enzyme activity. It suggested that enzymes bound to bacteria and other organic
      particles also would significantly contribute to the total enzyme activity of the
      fluid. Since organic particles are themselves usually colonized by attached and
      highly active bacteria, it is possible that microbe-derived enzymes also play an
      important role in nutrient recycling within the fluid and affect the metabolism
      of the Nepenthes pitcher plant.

PMID- 21949873
TI  - When and where of auditory spatial processing in cortex: a novel approach using
      electrotomography.
AB  - The modulation of brain activity as a function of auditory location was
      investigated using electro-encephalography in combination with standardized low
      resolution brain electromagnetic tomography. Auditory stimuli were presented at
      various positions under anechoic conditions in free-field space, thus providing
      the complete set of natural spatial cues. Variation of electrical activity in
      cortical areas depending on sound location was analyzed by contrasts between
      sound locations at the time of the N1 and P2 responses of the auditory evoked
      potential. A clear-cut double dissociation with respect to the cortical locations
      and the points in time was found, indicating spatial processing (1) in the
      primary auditory cortex and posterodorsal auditory cortical pathway at the time
      of the N1, and (2) in the anteroventral pathway regions about 100 ms later at the
      time of the P2. Thus, it seems as if both auditory pathways are involved in
      spatial analysis but at different points in time. It is possible that the late
      processing in the anteroventral auditory network reflected the sharing of this
      region by analysis of object-feature information and spectral localization cues
      or even the integration of spatial and non-spatial sound features.

PMID- 21949874
TI  - Phenotypic landscape of Saccharomyces cerevisiae during wine fermentation:
      evidence for origin-dependent metabolic traits.
AB  - The species Saccharomyces cerevisiae includes natural strains, clinical isolates,
      and a large number of strains used in human activities. The aim of this work was
      to investigate how the adaptation to a broad range of ecological niches may have
      selectively shaped the yeast metabolic network to generate specific phenotypes.
      Using 72 S. cerevisiae strains collected from various sources, we provide, for
      the first time, a population-scale picture of the fermentative metabolic traits
      found in the S. cerevisiae species under wine making conditions. Considerable
      phenotypic variation was found suggesting that this yeast employs diverse
      metabolic strategies to face environmental constraints. Several groups of strains
      can be distinguished from the entire population on the basis of specific traits.
      Strains accustomed to growing in the presence of high sugar concentrations, such
      as wine yeasts and strains obtained from fruits, were able to achieve
      fermentation, whereas natural yeasts isolated from "poor-sugar" environments,
      such as oak trees or plants, were not. Commercial wine yeasts clearly appeared as
      a subset of vineyard isolates, and were mainly differentiated by their
      fermentative performances as well as their low acetate production. Overall, the
      emergence of the origin-dependent properties of the strains provides evidence for
      a phenotypic evolution driven by environmental constraints and/or human selection
      within S. cerevisiae.

PMID- 21949875
TI  - Context modulates the ERP signature of contour integration.
AB  - We investigated how the electrophysiological signature of contour integration is
      changed by the context in which a contour is embedded. Specifically, we
      manipulated the orientations of Gabor elements surrounding an embedded shape
      outline. The amplitudes of early visual components over posterior scalp regions
      were changed by the presence of a contour, and by the orientation of elements
      surrounding the contour. Differences in context type had an effect on the early
      P1 and N1 components, but not on the later P2 component. The presence of a
      contour had an effect on the N1 and P2 components, but not on the earlier P1
      component. A modulatory effect of context on contour integration was observed on
      the N1 component. These results highlight the importance of the context in which
      contour integration takes place.

PMID- 21949876
TI  - A single amino acid mutation in SNAP-25 induces anxiety-related behavior in
      mouse.
AB  - Synaptosomal-associated protein of 25 kDa (SNAP-25) is a presynaptic protein
      essential for neurotransmitter release. Previously, we demonstrate that protein
      kinase C (PKC) phosphorylates Ser(187) of SNAP-25, and enhances neurotransmitter
      release by recruiting secretory vesicles near to the plasma membrane. As PKC is
      abundant in the brain and SNAP-25 is essential for synaptic transmission, SNAP-25
      phosphorylation is likely to play a crucial role in the central nervous system.
      We therefore generated a mutant mouse, substituting Ser(187) of SNAP-25 with Ala
      using "knock-in" technology. The most striking effect of the mutation was
      observed in their behavior. The homozygous mutant mice froze readily in response
      to environmental change, and showed strong anxiety-related behavior in general
      activity and light and dark preference tests. In addition, the mutant mice
      sometimes exhibited spontaneously occurring convulsive seizures. Microdialysis
      measurements revealed that serotonin and dopamine release were markedly reduced
      in amygdala. These results clearly indicate that PKC-dependent SNAP-25
      phosphorylation plays a critical role in the regulation of emotional behavior as
      well as the suppression of epileptic seizures, and the lack of enhancement of
      monoamine release is one of the possible mechanisms underlying these defects.

PMID- 21949877
TI  - Increased activity imbalance in fronto-subcortical circuits in adolescents with
      major depression.
AB  - BACKGROUND: A functional discrepancy exists in adolescents between frontal and
      subcortical regions due to differential regional maturational trajectories. It
      remains unknown how this functional discrepancy alters and whether the influence
      from the subcortical to the frontal system plays a primacy role in medication
      naive adolescent with major depressive disorder (MDD). METHODOLOGY/PRINCIPAL
      FINDINGS: Eighteen MDD and 18 healthy adolescents were enrolled. Depression and
      anxiety severity was assessed by the Short Mood and Feeling Questionnaire (SMFQ)
      and Screen for Child Anxiety Related Emotional Disorders (SCARED) respectively.
      The functional discrepancy was measured by the amplitude of low-frequency
      fluctuations (ALFF) of resting-state functional MRI signal. Correlation analysis
      was carried out between ALFF values and SMFQ and SCARED scores. Resting brain
      activity levels measured by ALFF was higher in the frontal cortex than that in
      the subcortical system involving mainly (para) limbic-striatal regions in both HC
      and MDD adolescents. The difference of ALFF values between frontal and
      subcortical systems was increased in MDD adolescents as compared with the
      controls. CONCLUSIONS/SIGNIFICANCE: The present study identified an increased
      imbalance of resting-state brain activity between the frontal cognitive control
      system and the (para) limbic-striatal emotional processing system in MDD
      adolescents. The findings may provide insights into the neural correlates of
      adolescent MDD.

PMID- 21949878
TI  - Aebp2 as an epigenetic regulator for neural crest cells.
AB  - Aebp2 is a potential targeting protein for the mammalian Polycomb Repression
      Complex 2 (PRC2). We generated a mutant mouse line disrupting the transcription
      of Aebp2 to investigate its in vivo roles. Aebp2-mutant homozygotes were
      embryonic lethal while heterozygotes survived to adulthood with fertility. In
      developing mouse embryos, Aebp2 is expressed mainly within cells of neural crest
      origin. In addition, many heterozygotes display a set of phenotypes, enlarged
      colon and hypopigmentation, similar to those observed in human patients with
      Hirschsprung's disease and Waardenburg syndrome. These phenotypes are usually
      caused by the absence of the neural crest-derived ganglia in hindguts and
      melanocytes. ChIP analyses demonstrated that the majority of the genes involved
      in the migration and development process of neural crest cells are downstream
      target genes of AEBP2 and PRC2. Furthermore, expression analyses confirmed that
      some of these genes are indeed affected in the Aebp2 heterozygotes. Taken
      together, these results suggest that Aebp2 may regulate the migration and
      development of the neural crest cells through the PRC2-mediated epigenetic
      mechanism.

PMID- 21949879
TI  - Economic feasibility of a new method to estimate mortality in crisis-affected and
      resource-poor settings.
AB  - INTRODUCTION: Mortality data provide essential evidence on the health status of
      populations in crisis-affected and resource-poor settings and to guide and assess
      relief operations. Retrospective surveys are commonly used to collect mortality
      data in such populations, but require substantial resources and have important
      methodological limitations. We evaluated the feasibility of an alternative method
      for rapidly quantifying mortality (the informant method). The study objective was
      to assess the economic feasibility of the informant method. METHODS: The
      informant method captures deaths through an exhaustive search for all deaths
      occurring in a population over a defined and recent recall period, using key
      community informants and next-of-kin of decedents. Between July and October 2008,
      we implemented and evaluated the informant method in: Kabul, Afghanistan; Mae La
      camp for Karen refugees, Thai-Burma border; Chiradzulu District, Malawi; and
      Lugufu and Mtabila refugee camps, Tanzania. We documented the time and cost
      inputs for the informant method in each site, and compared these with projections
      for hypothetical retrospective mortality surveys implemented in the same site
      with a 6 month recall period and with a 30 day recall period. FINDINGS: The
      informant method was estimated to require an average of 29% less time inputs and
      33% less monetary inputs across all four study sites when compared with
      retrospective surveys with a 6 month recall period, and 88% less time inputs and
      86% less monetary inputs when compared with retrospective surveys with a 1 month
      recall period. Verbal autopsy questionnaires were feasible and efficient,
      constituting only 4% of total person-time for the informant method's
      implementation in Chiradzulu District. CONCLUSIONS: The informant method requires
      fewer resources and incurs less respondent burden. The method's generally
      impressive feasibility and the near real-time mortality data it provides warrant
      further work to develop the method given the importance of mortality measurement
      in such settings.

PMID- 21949880
TI  - An ENU-induced mutation of Nrg1 causes dilated pupils and a reduction in
      muscarinic receptors in the sphincter pupillae.
AB  - BACKGROUND: N-ethyl-N-nitrosourea (ENU)-induced mutagenesis is a powerful tool
      for the study of gene function and the generation of human disease models. A
      large number of mouse mutants obtained by ENU-induced mutagenesis with a variety
      of phenotypes have been recovered. However, after genetic confirmation testing,
      only approximately 50% of the abnormal phenotypes were found to be heritable.
      METHODOLOGY/PRINCIPAL FINDINGS: A mouse mutant, Dp1, with a dilated pupil
      phenotype was induced with an N-ethyl-N-nitrosourea (ENU) mutagenesis strategy.
      Sequence analysis for Nrg1 reveals a G>A base substitution that flanks exon E59,
      encoding for an EGFbeta domain, in the 5' splice donor site. The mutation affects
      but does not abolish the splicing of EGFbeta-type Nrg1 mRNA in Dp1 mice and
      produces several different transcripts by activating other, cryptic splice sites.
      These types of protein isoforms are expected, and the result shows that, in the
      mutant, the effect is a decrease in but not an elimination of the high affinity
      EGFbeta-type Nrg1 isoforms. This is partially compensated for by an increase in
      expression of the low affinity alpha forms or inactive proteins, suggesting that
      the mutation results in a hypomorphic allele. Interestingly, genetic model
      testing shows that Dp1 is a mutation that results in a dilated pupil phenotype
      that is inherited with very low penetrance when heterozygous and with complete
      penetrance when homozygous. Pharmacological and immunohistochemical tests show a
      reduction of muscarinic (M) receptors in the sphincter pupillae of Dp1 mice,
      which is a major cause of dilated pupils. CONCLUSIONS/SIGNIFICANCE: This study is
      the first report of an Nrg1 mutation being associated with a dilated pupil
      phenotype and the reduction of M receptors. This report may help in establishing
      more mutant mouse lines and models of human genetic disease and can be applied to
      other organisms. Dp1 mice are a valuable resource for the further clarification
      of Nrg1 biological function.

PMID- 21949881
TI  - Targeting pannexin1 improves seizure outcome.
AB  - Imbalance of the excitatory neurotransmitter glutamate and of the inhibitory
      neurotransmitter GABA is one of several causes of seizures. ATP has also been
      implicated in epilepsy. However, little is known about the mechanisms involved in
      the release of ATP from cells and the consequences of the altered ATP signaling
      during seizures. Pannexin1 (Panx1) is found in astrocytes and in neurons at high
      levels in the embryonic and young postnatal brain, declining in adulthood. Panx1
      forms large-conductance voltage sensitive plasma membrane channels permeable to
      ATP that are also activated by elevated extracellular K(+) and following P2
      receptor stimulation. Based on these properties, we hypothesized that Panx1
      channels may contribute to seizures by increasing the levels of extracellular
      ATP. Using pharmacological tools and two transgenic mice deficient for Panx1 we
      show here that interference with Panx1 ameliorates the outcome and shortens the
      duration of kainic acid-induced status epilepticus. These data thus indicate that
      the activation of Panx1 in juvenile mouse hippocampi contributes to neuronal
      hyperactivity in seizures.

PMID- 21949882
TI  - Schizosaccharomyces pombe Ofd2 is a nuclear 2-oxoglutarate and iron dependent
      dioxygenase interacting with histones.
AB  - 2-Oxoglutarate (2OG) dependent dioxygenases are ubiquitous iron containing
      enzymes that couple substrate oxidation to the conversion of 2OG to succinate and
      carbon dioxide. They participate in a wide range of biological processes
      including collagen biosynthesis, fatty acid metabolism, hypoxic sensing and
      demethylation of nucleic acids and histones. Although substantial progress has
      been made in elucidating their function, the role of many 2OG dioxygenases
      remains enigmatic. Here we have studied the 2OG and iron (Fe(II)) dependent
      dioxygenase Ofd2 in Schizosaccharomyces pombe, a member of the AlkB subfamily of
      dioxygenases. We show that decarboxylation of 2OG by recombinant Ofd2 is
      dependent on Fe(II) and a histidine residue predicted to be involved in Fe(II)
      coordination. The decarboxylase activity of Ofd2 is stimulated by histones, and
      H2A has the strongest effect. Ofd2 interacts with all four core histones,
      however, only very weakly with H4. Our results define a new subclass of AlkB
      proteins interacting with histones, which also might comprise some of the human
      AlkB homologs with unknown function.

PMID- 21949883
TI  - Screening for EGFR and KRAS mutations in endobronchial ultrasound derived
      transbronchial needle aspirates in non-small cell lung cancer using COLD-PCR.
AB  - EGFR mutations correlate with improved clinical outcome whereas KRAS mutations
      are associated with lack of response to tyrosine kinase inhibitors in patients
      with non-small cell lung cancer (NSCLC). Endobronchial ultrasound (EBUS)
      transbronchial needle aspiration (TBNA) is being increasingly used in the
      management of NSCLC. Co-amplification at lower denaturation temperature (COLD)
      polymerase chain reaction (PCR) (COLD-PCR) is a sensitive assay for the detection
      of genetic mutations in solid tumours. This study assessed the feasibility of
      using COLD-PCR to screen for EGFR and KRAS mutations in cytology samples obtained
      by EBUS-TBNA in routine clinical practice. Samples obtained from NSCLC patients
      undergoing EBUS-TBNA were evaluated according to our standard clinical protocols.
      DNA extracted from these samples was subjected to COLD-PCR to amplify exons 18-21
      of EGFR and exons two and three of KRAS followed by direct sequencing. Mutation
      analysis was performed in 131 of 132 (99.3%) NSCLC patients (70F/62M) with
      confirmed lymph node metastases (94/132 (71.2%) adenocarcinoma; 17/132 (12.8%)
      squamous cell; 2/132 (0.15%) large cell neuroendocrine; 1/132 (0.07%) large cell
      carcinoma; 18/132 (13.6%) NSCL-not otherwise specified (NOS)). Molecular analysis
      of all EGFR and KRAS target sequences was achieved in 126 of 132 (95.5%) and 130
      of 132 (98.4%) of cases respectively. EGFR mutations were identified in 13
      (10.5%) of fully evaluated cases (11 in adenocarcinoma and two in NSCLC-NOS)
      including two novel mutations. KRAS mutations were identified in 23 (17.5%) of
      fully analysed patient samples (18 adenocarcinoma and five NSCLC-NOS). We
      conclude that EBUS-TBNA of lymph nodes infiltrated by NSCLC can provide
      sufficient tumour material for EGFR and KRAS mutation analysis in most patients,
      and that COLD-PCR and sequencing is a robust screening assay for EGFR and KRAS
      mutation analysis in this clinical context.

PMID- 21949884
TI  - Dopamine regulates angiogenesis in normal dermal wound tissues.
AB  - Cutaneous wound healing is a normal physiological process and comprises different
      phases. Among these phases, angiogenesis or new blood vessel formation in wound
      tissue plays an important role. Skin is richly supplied by sympathetic nerves and
      evidences indicate the significant role of the sympathetic nervous system in
      cutaneous wound healing. Dopamine (DA) is an important catecholamine
      neurotransmitter released by the sympathetic nerve endings and recent studies
      have demonstrated the potent anti-angiogenic action of DA, which is mediated
      through its D(2) DA receptors. We therefore postulate that this endogenous
      catecholamine neurotransmitter may have a role in the neovascularization of
      dermal wound tissues and subsequently in the process of wound healing. In the
      present study, the therapeutic efficacy of D(2) DA receptor antagonist has been
      investigated for faster wound healing in a murine model of full thickness dermal
      wound. Our results indicate that treatment with specific D(2) DA receptor
      antagonist significantly expedites the process of full thickness normal dermal
      wound healing in mice by inducing angiogenesis in wound tissues. The underlined
      mechanisms have been attributed to the up-regulation of homeobox transcription
      factor HoxD3 and its target alpha5beta1 integrin, which play a pivotal role in
      wound angiogenesis. Since D(2) DA receptor antagonists are already in clinical
      use for other disorders, these results have significant translational value from
      the bench to the bedside for efficient wound management along with other
      conventional treatment modalities.

PMID- 21949885
TI  - Quantal glutamate release is essential for reliable neuronal encodings in
      cerebral networks.
AB  - BACKGROUND: The neurons and synapses work coordinately to program the brain codes
      of controlling cognition and behaviors. Spike patterns at the presynaptic neurons
      regulate synaptic transmission. The quantitative regulations of synapse dynamics
      in spike encoding at the postsynaptic neurons remain unclear.
      METHODOLOGY/PRINCIPAL FINDINGS: With dual whole-cell recordings at synapse-paired
      cells in mouse cortical slices, we have investigated the regulation of synapse
      dynamics to neuronal spike encoding at cerebral circuits assembled by pyramidal
      neurons and GABAergic ones. Our studies at unitary synapses show that
      postsynaptic responses are constant over time, such as glutamate receptor-channel
      currents at GABAergic neurons and glutamate transport currents at astrocytes,
      indicating quantal glutamate release. In terms of its physiological impact, our
      results demonstrate that the signals integrated from quantal glutamatergic
      synapses drive spike encoding at GABAergic neurons reliably, which in turn
      precisely set spike encoding at pyramidal neurons through feedback inhibition.
      CONCLUSION/SIGNIFICANCE: Our studies provide the evidences for the quantal
      glutamate release to drive the spike encodings precisely in cortical circuits,
      which may be essential for programming the reliable codes in the brain to manage
      well-organized behaviors.

PMID- 21949886
TI  - Mast cell accumulation in glioblastoma with a potential role for stem cell factor
      and chemokine CXCL12.
AB  - Glioblastoma multiforme (GBM) is the most common and malignant form of glioma
      with high mortality and no cure. Many human cancers maintain a complex
      inflammatory program triggering rapid recruitment of inflammatory cells,
      including mast cells (MCs), to the tumor site. However, the potential
      contribution of MCs in glioma has not been addressed previously. Here we report
      for the first time that MCs infiltrate KRas+Akt-induced gliomas, using the
      RCAS/TV-a system, where KRas and Akt are transduced by RCAS into the brains of
      neonatal Gtv-a- or Ntv-a transgenic mice lacking Ink4a or Arf. The most abundant
      MC infiltration was observed in high-grade gliomas of Arf-/- mice. MC
      accumulation could be localized to the vicinity of glioma-associated vessels but
      also within the tumor mass. Importantly, proliferating MCs were detected,
      suggesting that the MC accumulation was caused by local expansion of the MC
      population. In line with these findings, strong expression of stem cell factor
      (SCF), i.e. the main MC growth factor, was detected, in particular around tumor
      blood vessels. Further, glioma cells expressed the MC chemotaxin CXCL12 and MCs
      expressed the corresponding receptor, i.e. CXCR4, suggesting that MCs could be
      attracted to the tumor through the CXCL12/CXCR4 axis. Supporting a role for MCs
      in glioma, strong MC infiltration was detected in human glioma, where GBMs
      contained significantly higher MC numbers than grade II tumors did. Moreover,
      human GBMs were positive for CXCL12 and the infiltrating MCs were positive for
      CXCR4. In conclusion, we provide the first evidence for a role for MCs in glioma.

PMID- 21949887
TI  - Evaluation of intra-host variants of the entire hepatitis B virus genome.
AB  - Genetic analysis of hepatitis B virus (HBV) frequently involves study of intra
      host variants, identification of which is commonly achieved using short regions
      of the HBV genome. However, the use of short sequences significantly limits
      evaluation of genetic relatedness among HBV strains. Although analysis of HBV
      complete genomes using genetic cloning has been developed, its application is
      highly labor intensive and practiced only infrequently. We describe here a novel
      approach to whole genome (WG) HBV quasispecies analysis based on end-point,
      limiting-dilution real-time PCR (EPLD-PCR) for amplification of single HBV genome
      variants, and their subsequent sequencing. EPLD-PCR was used to analyze WG
      quasispecies from serum samples of patients (n = 38) infected with HBV genotypes
      A, B, C, D, E and G. Phylogenetic analysis of the EPLD-isolated HBV-WG
      quasispecies showed the presence of mixed genotypes, recombinant variants and sub
      populations of the virus. A critical observation was that HBV-WG consensus
      sequences obtained by direct sequencing of PCR fragments without EPLD are
      genetically close, but not always identical to the major HBV variants in the
      intra-host population, thus indicating that consensus sequences should be
      judiciously used in genetic analysis. Sequence-based studies of HBV WG
      quasispecies should afford a more accurate assessment of HBV evolution in various
      clinical and epidemiological settings.

PMID- 21949888
TI  - Dynamic expression of cadherins regulates vocal development in a songbird.
AB  - BACKGROUND: Since, similarly to humans, songbirds learn their vocalization
      through imitation during their juvenile stage, they have often been used as model
      animals to study the mechanisms of human verbal learning. Numerous anatomical and
      physiological studies have suggested that songbirds have a neural network called
      'song system' specialized for vocal learning and production in their brain.
      However, it still remains unknown what molecular mechanisms regulate their vocal
      development. It has been suggested that type-II cadherins are involved in synapse
      formation and function. Previously, we found that type-II cadherin expressions
      are switched in the robust nucleus of arcopallium from cadherin-7-positive to
      cadherin-6B-positive during the phase from sensory to sensorimotor learning stage
      in a songbird, the Bengalese finch. Furthermore, in vitro analysis using cultured
      rat hippocampal neurons revealed that cadherin-6B enhanced and cadherin-7
      suppressed the frequency of miniature excitatory postsynaptic currents via
      regulating dendritic spine morphology. METHODOLOGY/PRINCIPAL FINDINGS: To explore
      the role of cadherins in vocal development, we performed an in vivo behavioral
      analysis of cadherin function with lentiviral vectors. Overexpression of cadherin
      7 in the juvenile and the adult stages resulted in severe defects in vocal
      production. In both cases, harmonic sounds typically seen in the adult Bengalese
      finch songs were particularly affected. CONCLUSIONS/SIGNIFICANCE: Our results
      suggest that cadherins control vocal production, particularly harmonic sounds,
      probably by modulating neuronal morphology of the RA nucleus. It appears that the
      switching of cadherin expressions from sensory to sensorimotor learning stage
      enhances vocal production ability to make various types of vocalization that is
      essential for sensorimotor learning in a trial and error manner.

PMID- 21949889
TI  - A membrane-bound vertebrate globin.
AB  - The family of vertebrate globins includes hemoglobin, myoglobin, and other O(2)
      binding proteins of yet unclear functions. Among these, globin X is restricted to
      fish and amphibians. Zebrafish (Danio rerio) globin X is expressed at low levels
      in neurons of the central nervous system and appears to be associated with the
      sensory system. The protein harbors a unique N-terminal extension with putative N
      myristoylation and S-palmitoylation sites, suggesting membrane-association.
      Intracellular localization and transport of globin X was studied in 3T3 cells
      employing green fluorescence protein fusion constructs. Both myristoylation and
      palmitoylation sites are required for correct targeting and membrane localization
      of globin X. To the best of our knowledge, this is the first time that a
      vertebrate globin has been identified as component of the cell membrane. Globin X
      has a hexacoordinate binding scheme and displays cooperative O(2) binding with a
      variable affinity (P(50)~1.3-12.5 torr), depending on buffer conditions. A
      respiratory function of globin X is unlikely, but analogous to some prokaryotic
      membrane-globins it may either protect the lipids in cell membrane from oxidation
      or may act as a redox-sensing or signaling protein.

PMID- 21949890
TI  - Resolution of praziquantel.
AB  - BACKGROUND: Praziquantel remains the drug of choice for the worldwide treatment
      and control of schistosomiasis. The drug is synthesized and administered as a
      racemate. Use of the pure active enantiomer would be desirable since the inactive
      enantiomer is associated with side effects and is responsible for the extremely
      bitter taste of the pill. METHODOLOGY/PRINCIPAL FINDINGS: We have identified two
      resolution approaches toward the production of praziquantel as a single
      enantiomer. One approach starts with commercially available praziquantel and
      involves a hydrolysis to an intermediate amine, which is resolved with a
      derivative of tartaric acid. This method was discovered through an open
      collaboration on the internet. The second method, identified by a contract
      research organisation, employs a different intermediate that may be resolved with
      tartaric acid itself. CONCLUSIONS/SIGNIFICANCE: Both resolution procedures
      identified show promise for the large-scale, economically viable production of
      praziquantel as a single enantiomer for a low price. Additionally, they may be
      employed by laboratories for the production of smaller amounts of enantiopure
      drug for research purposes that should be useful in, for example, elucidation of
      the drug's mechanism of action.

PMID- 21949891
TI  - Risk of Buruli ulcer and detection of Mycobacterium ulcerans in mosquitoes in
      southeastern Australia.
AB  - BACKGROUND: Buruli ulcer (BU) is a destructive skin condition caused by infection
      with the environmental bacterium, Mycobacterium ulcerans. The mode of
      transmission of M. ulcerans is not completely understood, but several studies
      have explored the role of biting insects. In this study, we tested for an
      association between the detection of M. ulcerans in mosquitoes and the risk of BU
      disease in humans in an endemic area of southeastern Australia.
      METHODOLOGY/PRINCIPAL FINDINGS: Adult mosquitoes were trapped in seven towns on
      the Bellarine Peninsula in Victoria, Australia, from December 2004 to December
      2009 and screened for M. ulcerans by real-time PCR. The number of laboratory
      confirmed cases of BU in permanent residents of these towns diagnosed during the
      same period was tallied to determine the average cumulative incidence of BU in
      each location. Pearson's correlation coefficient (r) was calculated for the
      proportion of M. ulcerans-positive mosquitoes per town correlated with the
      incidence of BU per town. We found a strong dose-response relationship between
      the detection of M. ulcerans in mosquitoes and the risk of human disease (r,
      0.99; 95% CI, 0.92-0.99; p < 0.001). CONCLUSIONS/SIGNIFICANCE: The results of
      this study strengthen the hypothesis that mosquitoes are involved in the
      transmission of M. ulcerans in southeastern Australia. This has implications for
      the development of intervention strategies to control and prevent BU.

PMID- 21949892
TI  - Iquitos virus: a novel reassortant Orthobunyavirus associated with human illness
      in Peru.
AB  - Oropouche (ORO) virus, a member of the Simbu serogroup, is one of the few human
      pathogens in the Orthobunyavirus genus in the family Bunyaviridae. Genetic
      analyses of ORO-like strains from Iquitos, Peru, identified a novel reassortant
      containing the S and L segments of ORO virus and the M segment of a novel Simbu
      serogroup virus. This new pathogen, which we named Iquitos (IQT) virus, was first
      isolated during 1999 from a febrile patient in Iquitos, an Amazonian city in
      Peru. Subsequently, the virus was identified as the cause of outbreaks of
      "Oropouche fever" during 2005 and 2006 in Iquitos. In addition to the
      identification of 17 isolates of IQT virus between 1999 and 2006, surveys for
      neutralizing antibody among Iquitos residents revealed prevalence rates of 14.9%
      for ORO virus and 15.4% for IQT virus. Limited studies indicate that prior
      infection with ORO virus does not seem to protect against disease caused with the
      IQT virus infection. Identification of a new Orthobunyavirus human pathogen in
      the Amazon region of Peru highlights the need for strengthening surveillance
      activities and laboratory capabilities, and investigating the emergence of new
      pathogens in tropical regions of South America.

PMID- 21949893
TI  - Utility of repeated praziquantel dosing in the treatment of schistosomiasis in
      high-risk communities in Africa: a systematic review.
AB  - BACKGROUND: Controversy persists about the optimal approach to drug-based control
      of schistosomiasis in high-risk communities. In a systematic review of published
      studies, we examined evidence for incremental benefits from repeated praziquantel
      dosing, given 2 to 8 weeks after an initial dose, in Schistosoma-endemic areas of
      Africa. METHODOLOGY/PRINCIPAL FINDINGS: We performed systematic searches of
      electronic databases PubMed and EMBASE for relevant data using search terms
      'schistosomiasis', 'dosing' and 'praziquantel' and hand searches of personal
      collections and bibliographies of recovered articles. In 10 reports meeting study
      criteria, improvements in parasitological treatment outcomes after two doses of
      praziquantel were greater for S. mansoni infection than for S. haematobium
      infection. Observed cure rates (positive to negative conversion in egg detection
      assays) were, for S. mansoni, 69-91% cure after two doses vs. 42-79% after one
      dose and, for S. haematobium, 46-99% cure after two doses vs. 37-93% after a
      single dose. Treatment benefits in terms of reduction in intensity (mean egg
      count) were also different for the two species-for S. mansoni, the 2-dose regimen
      yielded an weighted average 89% reduction in standardized egg counts compared to
      a 83% reduction after one dose; for S. haematobium, two doses gave a 93%
      reduction compared to a 94% reduction with a single dose. Cost-effectiveness
      analysis was performed based on Markov life path modeling.
      CONCLUSIONS/SIGNIFICANCE: Although schedules for repeated treatment with
      praziquantel require greater inputs in terms of direct costs and community
      participation, there are incremental benefits to this approach at an estimated
      cost of $153 (S. mansoni)-$211 (S. haematobium) per additional lifetime QALY
      gained by double treatment in school-based programs. More rapid reduction of
      infection-related disease may improve program adherence, and if, as an
      externality of the program, transmission can be reduced through more effective
      coverage, significant additional benefits are expected to accrue in the targeted
      communities.

PMID- 21949894
TI  - Epidemiologic relationship between Toscana virus infection and Leishmania
      infantum due to common exposure to Phlebotomus perniciosus sandfly vector.
AB  - Sand flies are recognised vectors of parasites in the genus Leishmania and a
      number of arthropod-borne viruses, in particular viruses within the genus
      Phlebovirus, family Bunyaviridae. In southern France, Toscana phlebovirus (TOSV)
      is recognized as a prominent cause of summer meningitis. Since Leishmania and
      TOSV have a common vector (Phlebotomus perniciosus), an epidemiologic link has
      been assumed for a long time. However, there is no scientific evidence of such a
      link between human leishmaniosis and phleboviral infections. To identify a
      possible link, we investigated the presence and distribution of antibodies
      against these two microorganisms (i) in individuals and (ii) at a spatial level
      in the city of Marseille (south-eastern France). Five hundred sera were selected
      randomly in the biobank of the Department of Parasitology of the Public Hospitals
      of Marseille. All sera were previously tested for IgG against Leishmania by
      Western Blotting, and TOSV IgG were detected by indirect immunofluorescence. The
      seropositivity rates were 21.4% for TOSV and 28% for Leishmania. Statistical
      analysis demonstrated that seropositivity for one pathogen was significantly
      associated with seropositivity to the other pathogen. This result provided the
      first robust evidence for the existence of an epidemiological relationship
      between Leishmania infantum and TOSV. Addresses of tested patients were
      geolocalized and integrated into Geographical Information System software, in
      order to test spatial relationship between the two pathogens. Spatial analysis
      did not allow to identify (i) specific patterns for the spatial distribution of
      positive serological results for TOSV or Leishmania, and (ii) a spatial
      relationship between Leishmania and TOSV positive serological results. This may
      reflect the fact that the sample studied was not powerful enough to demonstrate
      either a spatial clustering or co-location, i.e. that the actual risk exposure
      area is smaller than the mean of distance between patients in our study (245 m).

PMID- 21949895
TI  - The long-term effect of current and new interventions on the new case detection
      of leprosy: a modeling study.
AB  - BACKGROUND: Although the number of newly detected leprosy cases has decreased
      globally, a quarter of a million new cases are detected annually and eradication
      remains far away. Current options for leprosy prevention are contact tracing and
      BCG vaccination of infants. Future options may include chemoprophylaxis and early
      diagnosis of subclinical infections. This study compared the predicted trends in
      leprosy case detection of future intervention strategies. METHODS: Seven leprosy
      intervention scenarios were investigated with a microsimulation model (SIMCOLEP)
      to predict future leprosy trends. The baseline scenario consisted of passive case
      detection, multidrug therapy, contact tracing, and BCG vaccination of infants.
      The other six scenarios were modifications of the baseline, as follows: no
      contact tracing; with chemoprophylaxis; with early diagnosis of subclinical
      infections; replacement of the BCG vaccine with a new tuberculosis vaccine
      ineffective against Mycobacterium leprae ("no BCG"); no BCG with
      chemoprophylaxis; and no BCG with early diagnosis. FINDINGS: Without contact
      tracing, the model predicted an initial drop in the new case detection rate due
      to a delay in detecting clinical cases among contacts. Eventually, this scenario
      would lead to new case detection rates higher than the baseline program. Both
      chemoprophylaxis and early diagnosis would prevent new cases due to a reduction
      of the infectious period of subclinical cases by detection and cure of these
      cases. Also, replacing BCG would increase the new case detection rate of leprosy,
      but this effect could be offset with either chemoprophylaxis or early diagnosis.
      CONCLUSIONS: This study showed that the leprosy incidence would be reduced
      substantially by good BCG vaccine coverage and the combined strategies of contact
      tracing, early diagnosis, and treatment of infection and/or chemoprophylaxis
      among household contacts. To effectively interrupt the transmission of M. leprae,
      it is crucial to continue developing immuno- and chemoprophylaxis strategies and
      an effective test for diagnosing subclinical infections.

PMID- 21949897
TI  - Vegetation and the importance of insecticide-treated target siting for control of
      Glossina fuscipes fuscipes.
AB  - Control of tsetse flies using insecticide-treated targets is often hampered by
      vegetation re-growth and encroachment which obscures a target and renders it less
      effective. Potentially this is of particular concern for the newly developed
      small targets (0.25 high * 0.5 m wide) which show promise for cost-efficient
      control of Palpalis group tsetse flies. Consequently the performance of a small
      target was investigated for Glossina fuscipes fuscipes in Kenya, when the target
      was obscured following the placement of vegetation to simulate various degrees of
      natural bush encroachment. Catches decreased significantly only when the target
      was obscured by more than 80%. Even if a small target is underneath a very low
      overhanging bush (0.5 m above ground), the numbers of G. f. fuscipes decreased by
      only about 30% compared to a target in the open. We show that the efficiency of
      the small targets, even in small (1 m diameter) clearings, is largely
      uncompromised by vegetation re-growth because G. f. fuscipes readily enter
      between and under vegetation. The essential characteristic is that there should
      be some openings between vegetation. This implies that for this important vector
      of HAT, and possibly other Palpalis group flies, a smaller initial clearance zone
      around targets can be made and longer interval between site maintenance visits is
      possible both of which will result in cost savings for large scale operations. We
      also investigated and discuss other site features e.g. large solid objects and
      position in relation to the water's edge in terms of the efficacy of the small
      targets.

PMID- 21949896
TI  - Towards an optimal design of target for tsetse control: comparisons of novel
      targets for the control of Palpalis group tsetse in West Africa.
AB  - BACKGROUND: Tsetse flies of the Palpalis group are the main vectors of sleeping
      sickness in Africa. Insecticide impregnated targets are one of the most effective
      tools for control. However, the cost of these devices still represents a
      constraint to their wider use. The objective was therefore to improve the cost
      effectiveness of currently used devices. METHODOLOGY/PRINCIPAL FINDINGS:
      Experiments were performed on three tsetse species, namely Glossina palpalis
      gambiensis and G. tachinoides in Burkina Faso and G. p. palpalis in Cote
      d'Ivoire. The 1 * 1 m(2) black blue black target commonly used in W. Africa was
      used as the standard, and effects of changes in target size, shape, and the use
      of netting instead of black cloth were measured. Regarding overall target shape,
      we observed that horizontal targets (i.e. wider than they were high) killed 1.6
      5x more G. p. gambiensis and G. tachinoides than vertical ones (i.e. higher than
      they were wide) (P < 0.001). For the three tsetse species including G. p.
      palpalis, catches were highly correlated with the size of the target. However,
      beyond the size of 0.75 m, there was no increase in catches. Replacing the black
      cloth of the target by netting was the most cost efficient for all three species.
      CONCLUSION/SIGNIFICANCE: Reducing the size of the current 1*1 m black-blue-black
      target to horizontal designs of around 50 cm and replacing black cloth by netting
      will improve cost effectiveness six-fold for both G. p. gambiensis and G.
      tachinoides. Studying the visual responses of tsetse to different designs of
      target has allowed us to design more cost-effective devices for the effective
      control of sleeping sickness and animal trypanosomiasis in Africa.

PMID- 21949899
TI  - Lipid-lowering and antioxidative activities of aqueous extracts of Ocimum sanctum
      L. leaves in rats fed with a high-cholesterol diet.
AB  - The present study was conducted to investigate the lipid-lowering and
      antioxidative activities of Ocimum sanctum L. (OS) leaf extracts in liver and
      heart of rats fed with high-cholesterol (HC) diet for seven weeks. The results
      shows that OS suppressed the high levels of serum lipid profile and hepatic lipid
      content without significant effects on fecal lipid excretion. Fecal bile acids
      excretion was increased in HC rats treated with OS. The high serum levels of
      TBARS as well as AST, ALT, AP, LDH, CK-MB significantly decreased in HC rats
      treated with OS. OS suppressed the high level of TABARS and raised the low
      activities of GPx and CAT without any impact on SOD in the liver. As for the
      cardiac tissues, OS lowered the high level of TABARS, and raised the activities
      of GPx, CAT, and SOD. Histopathological results show that OS preserved the liver
      and myocardial tissues. It can be concluded that OS leaf extracts decreased
      hepatic and serum lipid profile, and provided the liver and cardiac tissues with
      protection from hypercholesterolemia. The lipid-lowering effect is probably due
      to the rise of bile acids synthesis using cholesterol as precursor, and
      antioxidative activity to protect liver from hypercholesterolemia.

PMID- 21949900
TI  - Nano delivers big: designing molecular missiles for cancer therapeutics.
AB  - Current first-line treatments for most cancers feature a short-list of highly
      potent and often target-blind interventions, including chemotherapy, radiation,
      and surgical excision. These treatments wreak considerable havoc upon non
      cancerous tissue and organs, resulting in deleterious and sometimes fatal side
      effects for the patient. In response, this past decade has witnessed the robust
      emergence of nanoparticles and, more relevantly, nanoparticle drug delivery
      systems (DDS), widely touted as the panacea of cancer therapeutics. While not a
      cure, nanoparticle DDS can successfully negotiate the clinical payoff between
      drug dosage and side effects by encompassing target-specific drug delivery
      strategies. The expanding library of nanoparticles includes lipoproteins,
      liposomes, dendrimers, polymers, metal and metal oxide nano-spheres and -rods,
      and carbon nanotubes, so do the modes of delivery. Importantly, however, the
      pharmaco-dynamics and -kinetics of these nano-complexes remain an urgent issue
      and a serious bottleneck in the transition from bench to bedside. This review
      addresses the rise of nanoparticle DDS platforms for cancer and explores concepts
      of gene/drug delivery and cytotoxicity in pre-clinical and clinical contexts. 

PMID- 21949901
TI  - The effects of molecular crowding on the structure and stability of g
      quadruplexes with an abasic site.
AB  - Both cellular environmental factors and chemical modifications critically affect
      the properties of nucleic acids. However, the structure and stability of DNA
      containing abasic sites under cell-mimicking molecular crowding conditions remain
      unclear. Here, we investigated the molecular crowding effects on the structure
      and stability of the G-quadruplexes including a single abasic site. Structural
      analysis by circular dichroism showed that molecular crowding by PEG200 did not
      affect the topology of the G-quadruplex structure with or without an abasic site.
      Thermodynamic analysis further demonstrated that the degree of stabilization of
      the G-quadruplex by molecular crowding decreased with substitution of an abasic
      site for a single guanine. Notably, we found that the molecular crowding effects
      on the enthalpy change for G-quadruplex formation had a linear relationship with
      the abasic site effects depending on its position. These results are useful for
      predicting the structure and stability of G-quadruplexes with abasic sites in the
      cell-mimicking conditions.

PMID- 21949898
TI  - Generation of reactive oxygen species during apoptosis induced by DNA-damaging
      agents and/or histone deacetylase inhibitors.
AB  - Reactive oxygen species play an important role in the process of apoptosis in
      many cell types. In this paper, we analyzed the role of ROS in DNA-damaging
      agents (actinomycin D or decitabine), which induced apoptosis of leukemia cell
      line CML-T1 and normal peripheral blood lymphocytes (PBL). The possibility of
      synergism with histone deacetylase inhibitors butyrate or SAHA is also reported.
      We found that in cancer cell line, ROS production significantly contributed to
      apoptosis triggering, while in normal lymphocytes treated by cytostatic or
      cytotoxic drugs, necrosis as well as apoptosis occurred and large heterogeneity
      of ROS production was measured. Combined treatment with histone deacetylase
      inhibitor did not potentiate actinomycin D action, whereas combination of
      decitabine and SAHA brought synergistic ROS generation and apoptotic features in
      CML cell line. Appropriate decrease of cell viability indicated promising
      therapeutic potential of this combination in CML, but side effects on normal PBL
      should be taken into attention.

PMID- 21949902
TI  - Antihypertensive Treatment in the Elderly and Very Elderly: Always "the Lower,
      the Better?".
AB  - Arterial hypertension (HT) is age dependent and, with the prolongation of life
      expectancy, affects more and more elderly people. In the elderly, HT is a risk
      factor for organ damage and cardiovascular (CV) events. Both pharmacologic and
      nonpharmacologic reduction of blood pressure (BP) is associated with a
      corresponding decrease in systolic-diastolic or isolated systolic HT. Clinical
      trials have shown that BP lowering is associated with a decrease in stroke and
      other CV events. Therefore, BP reduction per se appears more important than a
      particular class of antihypertensive drugs. The benefit of antihypertensive
      treatment has been confirmed up to the age of 80 years, remaining unclear in the
      octogenarians. The benefit in lowering diastolic BP between 80 and 90 mmHg is
      well established, while that of lowering systolic BP below 140 mmHg requires
      further confirmations.

PMID- 21949903
TI  - The gut hormones in appetite regulation.
AB  - Obesity has received much attention worldwide in association with an increased
      risk of cardiovascular diseases, diabetes, and cancer. At present, bariatric
      surgery is the only effective treatment for obesity in which long-term weight
      loss is achieved in patients. By contrast, pharmacological interventions for
      obesity are usually followed by weight regain. Although the exact mechanisms of
      long-term weight loss following bariatric surgery are yet to be fully elucidated,
      several gut hormones have been implicated. Gut hormones play a critical role in
      relaying signals of nutritional and energy status from the gut to the central
      nervous system, in order to regulate food intake. Cholecystokinin, peptide YY,
      pancreatic polypeptide, glucagon-like peptide-1, and oxyntomodulin act through
      distinct yet synergistic mechanisms to suppress appetite, whereas ghrelin
      stimulates food intake. Here, we discuss the role of gut hormones in the
      regulation of food intake and body weight.

PMID- 21949905
TI  - Treatment of steroid and cyclosporine-resistant idiopathic nephrotic syndrome in
      children.
AB  - Steroid-resistant nephrotic syndrome (SRNS) in children carries a significant
      risk of progression to end-stage renal failure (ESRF). We report a two-step
      protocol adapted in children with SRNS. Thirty-seven SRNS were treated with
      cyclosporine A (CyA) in association with prednisolone (alternate day) for 6
      months (first-step treatment). Twelve patients (32.4%) went into complete
      remission, and 2 (5.4%) got partial remission. The other 23 cases who were
      steroid and CyA resistant entered a second-step treatment with withdrawing
      steroids, with CyA (5 mg/kg/day) in association with mycophenolate mofetil (MMF)
      30 mg/kg/day for 6 months. Complete remission was observed in 11 cases (47.82%)
      and partial remission in 2 cases (8.7%). After two steps of treatment, 27/37
      children went into total remission. In steroid and CyA-resistant INS, the
      association of MMF with CyA was able to induce remission in about half cases
      without relevant side effects.

PMID- 21949904
TI  - Multimodal MRI neuroimaging biomarkers for cognitive normal adults, amnestic mild
      cognitive impairment, and Alzheimer's disease.
AB  - Multimodal magnetic resonance imaging (MRI) techniques have been developed to
      noninvasively measure structural, metabolic, hemodynamic and functional changes
      of the brain. These advantages have made MRI an important tool to investigate
      neurodegenerative disorders, including diagnosis, disease progression monitoring,
      and treatment efficacy evaluation. This paper discusses recent findings of the
      multimodal MRI in the context of surrogate biomarkers for identifying the risk
      for AD in normal cognitive (NC) adults, brain anatomical and functional
      alterations in amnestic mild cognitive impairment (aMCI), and Alzheimer's disease
      (AD) patients. Further developments of these techniques and the establishment of
      promising neuroimaging biomarkers will enhance our ability to diagnose aMCI and
      AD in their early stages and improve the assessment of therapeutic efficacy in
      these diseases in future clinical trials.

PMID- 21949906
TI  - Striatal Hypodensities, Not White Matter Hypodensities on CT, Are Associated with
      Late-Onset Depression in Alzheimer's Disease.
AB  - This study examined whether there were neuroanatomical differences evident on CT
      scans of individuals with dementia who differed on depression history.
      Neuroanatomical variables consisted of visual ratings of frontal lobe deep white
      matter, subcortical white matter, and subcortical gray matter hypodensities in
      the CT scans of 182 individuals from the Study of Dementia in Swedish Twins who
      were diagnosed with dementia and had information on depression history. Compared
      to individuals with Alzheimer's disease and no depression, individuals with
      Alzheimer's disease and late-onset depression (first depressive episode at age 60
      or over) had a greater number of striatal hypodensities (gray matter
      hypodensities in the caudate nucleus and lentiform nucleus). There were no
      significant differences in frontal lobe deep white matter or subcortical white
      matter. These findings suggest that late-onset depression may be a process that
      is distinct from the neurodegenerative changes caused by Alzheimer's disease.

PMID- 21949907
TI  - Effect of Plant Polyphenols on Adipokine Secretion from Human SGBS Adipocytes.
AB  - Introduction. Adipose tissue contributes to atherosclerosis with mechanisms
      related to adipokine secretion. Polyphenols may exhibit antiatherogenic
      properties. The aim of the study was to investigate the effects of three
      polyphenols, namely, quercetin, epigallocatechin gallate (EGCG), and resveratrol
      on adipokine secretion from cultured human adipocytes. Methods. Human SGBS
      adipocytes were treated with quercetin, EGCG, and resveratrol for 24 and 48
      hours. Visfatin, leptin, and adiponectin were measured in the supernatant.
      Results. Visfatin secretion was inhibited by quercetin 10 MUM by 16% and 24% at
      24 and 48 hours respectively. The corresponding changes for quercetin 25 MUM were
      47% and 48%. Resveratrol 25 MUM reduced visfatin by 28% and 38% at 24 and 48
      hours. EGCG did not have an effect on visfatin. None of tested polyphenols
      influenced leptin and adiponectin secretion. Conclusion. Quercetin and
      resveratrol significantly decreased visfatin secretion from SGBS adipocytes. This
      effect may contribute to their overall antiatherogenic properties.

PMID- 21949909
TI  - Paradigm shift in treatment of Alzheimer's disease: zinc therapy now a
      conscientious choice for care of individual patients.
AB  - Breakthrough in treatment of Alzheimer's disease with a shift from irrational
      dangerous chelation therapy to rational safe evidence based oral zinc therapy.
      Evidence based medicine: After synthesizing the best available clinical evidence
      I conclude that oral zinc therapy is a conscientious choice for treatment of free
      copper toxicosis in individual patients with Alzheimer's disease. Hypothesis 1:
      Age related free copper toxicosis is a causal factor in pathogenesis of
      Alzheimer's disease. There are 2 neurodegenerative diseases with abnormalities in
      copper metabolism: (a) the juvenile form with degeneration in the basal ganglia
      (Wilson's disease) and (b) the age related form with cortical neurodegeneration
      (Alzheimer's disease). Initially the hypothesis has been that neurodegeneration
      was caused by accumulation of copper in the brain but later experiences with
      treatment of Wilson's disease led to the conviction that free plasma copper is
      the toxic form of copper: it catalyzes amyloid formation thereby generating
      oxidative stress, free radicals and degeneration of cortical neurons. Hypothesis
      2: Oral zinc therapy is an effective and safe treatment of free copper toxicosis
      in Alzheimer's disease. Proposed dosage: 50 mg elementary zinc/day. Warning:
      Chelation therapy is irrational and dangerous in treatment of copper toxicosis in
      Alzheimer's disease.

PMID- 21949908
TI  - Neuroplasticity of the sensorimotor cortex during learning.
AB  - We will discuss some of the current issues in understanding plasticity in the
      sensorimotor (SM) cortices on the behavioral, neurophysiological, and synaptic
      levels. We will focus our paper on reaching and grasping movements in the rat. In
      addition, we will discuss our preliminary work utilizing inhibition of protein
      kinase Mzeta (PKMzeta), which has recently been shown necessary and sufficient
      for the maintenance of long-term potentiation (LTP) (Ling et al., 2002). With
      this new knowledge and inhibitors to this system, as well as the ability to
      overexpress this system, we can start to directly modulate LTP and determine its
      influence on behavior as well as network level processing dependent at least in
      part due to this form of LTP. We will also briefly introduce the use of brain
      machine interface (BMI) paradigms to ask questions about sensorimotor plasticity
      and discuss current analysis techniques that may help in our understanding of
      neuroplasticity.

PMID- 21949911
TI  - Risks to offspring of consanguineous marriage: we need straight, not crooked
      thinking.

PMID- 21949912
TI  - A pilot audit of a protocol for ambulatory investigation of predicted low-risk
      patients with possible pulmonary embolism.
AB  - BACKGROUND: Patients with possible pulmonary embolism (PE) commonly present to
      acute medical services. Research has led to the identification of low-risk
      patients suitable for ambulatory management. We report on a protocol designed to
      select low-risk patients for ambulatory investigation if confirmatory imaging is
      not available that day. METHODS: The protocol was piloted in the Emergency
      Department and Medical Assessment Area at the Royal Infirmary of Edinburgh. We
      retrospectively analysed electronic patient records in an open observational
      audit of all patients managed in the ambulatory arm over five months of use.
      RESULTS: We analysed 45 patients' records. Of these, 91.1% required imaging to
      confirm or refute PE, 62.2% received a computed tomography pulmonary angiogram
      (CTPA). In 25% of patients, PE was confirmed with musculoskeletal pain (22.7%),
      and respiratory tract infection (15.9%) the next most prevalent diagnoses.
      Alternative diagnoses was provided by CTPA in 32% of cases. We identified no
      adverse events or readmissions but individualised follow-up was not attempted.
      CONCLUSIONS: The data from this audit suggests this protocol can be applied to
      select and manage low-risk patients suitable for ambulatory investigation of
      possible PE. A larger prospective comparative study would be required to
      accurately define the safety and effectiveness of this protocol.

PMID- 21949913
TI  - Awareness and uptake of recommended vaccines among immunosuppressed patients.
AB  - The Green Book recommended in 2009 that immunosuppressed patients should be
      receiving the yearly seasonal flu vaccine, the pandemic swine influenza A H1N1/09
      vaccine and should have had the single pneumococcal vaccination. A retrospective
      audit in 2010 involving 60 immunosuppressed patients revealed that 83.3% of
      participants were aware of their entitlement to the vaccines. The majority were
      informed by their GP practice rather than the prescribing specialist. In 2009,
      70% of participants received the seasonal flu vaccine, 40% received the H1N1
      vaccine and 21.6% had received the pneumococcal vaccine. Reasons given for not
      receiving the recommended vaccines were lack of awareness, reported by 37.5%,
      followed by worries regarding side-effects reported by 25%. The data suggest that
      uptake rates, particularly for pneumococcal vaccination, could be improved with
      targeted information and promotion at the point of commencing immunosuppressants
      and approaching the influenza season. Prescribing physicians should take a more
      active role in routinely promoting and planning vaccination for at-risk groups
      and should provide information on how to receive the recommended vaccines and
      their side-effect profiles.

PMID- 21949914
TI  - Anaemia is of prognostic significance in patients with oesophageal
      adenocarcinoma.
AB  - Anaemia is common in a wide range of malignancies and individual studies have
      demonstrated it to be an independent prognostic marker for survival in certain
      cancer types. The study population consisted of 171 patients: 77 anaemic and 94
      non-anaemic. Sixty per cent of the study population had adenocarcinoma with 37%
      having squamous cell carcinoma. Late-stage disease occurred in 80% of
      individuals. There was no significant difference in survival times between the
      two groups (p=0.1), and after adjusting for confounding factors including age,
      sex, stage and physical status (p=0.8). Anaemic individuals with adenocarcinoma
      suffered a poorer survival probability compared to those with normal haemoglobon
      level (p=0.02). Anaemia is common at diagnosis in oesophageal cancer and was
      found to be a significant prognostic indicator of survival in adenocarcinoma, but
      not squamous cell carcinoma.

PMID- 21949916
TI  - Posterior reversible encephalopathy syndrome associated with deoxycoformycin and
      alemtuzumab.
AB  - Posterior reversible encephalopathy syndrome (PRES) is a combined clinical and
      radiological syndrome characterised by headaches, encephalopathy, seizures and
      visual loss. We present the case of a 55-year-old male who developed this
      condition following treatment with deoxycoformycin and alemtuzumab. We review the
      literature considering diagnosis, pathophysiology and optimal strategies for
      treatment of this condition.

PMID- 21949915
TI  - Central pontine myelinolysis without hyponatraemia.
AB  - A 55-year-old woman with a history of excess alcohol intake presented to the
      acute medical unit following concerns regarding her electrolyte disturbances.
      During correction of the electrolytes, the patient developed central pontine
      myelinolysis. The unusual features in the case were the absence of hyponatraemia
      which is usually associated with central pontine myelinolysis and also the good
      recovery that the patient made. Looking at the electrolyte changes, we suspect
      there may be a link to the rapid osmotic shifts occurring during refeeding and
      central pontine myelinolysis.

PMID- 21949917
TI  - Tumefactive multiple sclerosis in a young patient with hemiplegia and seizures
      associated with radiological appearance mimicking cerebral tumour.
AB  - Multiple sclerosis (MS) is the most common inflammatory demyelinating disease,
      affecting approximately one million adults worldwide. This paper describes a
      young female patient who presented to the acute medical team with generalised
      tonic-clonic seizures and right hemiplegia on a background of MS. Radiological
      imaging revealed a large ring enhancing lesion exerting mass effect. We describe
      an unusual form of MS and discuss diagnostic pitfalls of tumefactive
      demyelinating lesions which can be mistaken for brain tumours and abscesses.

PMID- 21949918
TI  - Two papers on carbamazepine-induced hypersensitivity and its relationship to HLA
      status.

PMID- 21949919
TI  - Revised diagnostic criteria for Marfan syndrome.

PMID- 21949920
TI  - Ring-fencing a budget for cancer drugs: is it fair?
AB  - Ring-fencing is defined as protecting funds for use in a specific area. In the
      National Health Service in the UK, various methods to ring-fence cancer have been
      employed over the years; more recently the Cancer Drugs Fund in England has
      enabled cancer drugs that would not normally be considered cost-effective to be
      provided to patients. This has created variation in provision between England and
      the devolved countries. While some would argue that ring-fencing allows major
      advances to be made in the treatment of a particular condition, others would
      argue that it is intrinsically unfair. In this debate, Graham and Cassidy have
      written an article arguing the affirmative position and Hughes and Duerden were
      invited to respond directly to their arguments. As with all the RCPE's 'Current
      controversies', the authors have been asked to take a deliberately polarised
      position and so the views they express may be somewhat overstated.

PMID- 21949921
TI  - Hyperuricaemia and gout.
AB  - Gout is increasing in prevalence throughout the world, particularly in developed
      countries. The causes are dietary--purine-rich foods, high saturated fats,
      fructose-containing drinks and alcohol. Gout is also drug-related and associated
      with increased obesity, hypertension, insulin resistance and metabolic syndrome.
      Although very readily treated, there is evidence that physicians fail to optimise
      the treatment and achieve low enough serum urate levels, while patients fail to
      comply with the treatment and dietary advice. Standard treatment of acute attacks
      is with non-steroidal anti-inflammatory drugs, colchicine or steroids. The
      standard urate-lowering agents are allopurinol and uricosuric agents. Newer urate
      lowering agents are now available for refractory gout. Increased understanding of
      the membrane transporters involved in urate excretion in the kidney and the genes
      that control them and of the way that sodium urate crystals cause inflammation
      via the innate immune system and the inflammasome offers hope for new therapeutic
      approaches.

PMID- 21949922
TI  - New biologics for rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory arthritis with many systemic
      manifestations. Several monoclonal antibodies targeting different components of
      the immune systems have been licensed for treatment of RA. Inflammatory cytokines
      such as interleukin-6 (IL-6) are found abundantly in the blood and the joints.
      The biologic effect of IL-6 on leukocyte, osteoclast, hepatocytes and bone marrow
      may mediate the articular and systemic inflammation in RA. Recently, an anti-IL-6
      receptor monoclonal antibody, tocilizumab, has been licensed for the treatment as
      monotherapy or in combination with methotrexate of moderate to severe RA, when
      disease modifying anti-rheumatic drugs or anti-tumour necrosis factors (TNF) have
      failed. It improves symptoms and signs as well as reducing joint damage.
      Tocilizumab monotherapy has been shown to be superior to methotrexate. Its side
      effects include infections, decrease in neutrophils, and increases in lipid and
      liver transaminases. Overall, tocilizumab has a well-defined and manageable
      safety profile that supports a favourable benefit/risk ratio for patients with
      RA.

PMID- 21949923
TI  - The challenges of renal replacement therapy and renal palliative care in the
      elderly.
AB  - The main aim of this review is to let general practitioners and physicians
      understand what happens to older patients after referral to the renal service.
      Usually, most patients will be managed completely by the renal team, either
      because the patient requires dialysis or because conservative but specialised
      care is appropriate. The recent increase in dialysis rate can mostly be accounted
      for by older patients for whom such demanding treatment was previously thought to
      be contraindicated. The decision to dialyse the elderly still remains difficult,
      with recent data suggesting that if there are significant comorbidities the
      survival advantage of dialysis in patients over 75 years of age is unlikely to be
      more than four months. Towards the end of life, conservative treatment is not
      simply a decision not to dialyse, but comprises active disease management,
      including treatment of anaemia and other supportive care, which may become
      increasingly complex, e.g. pain relief with fentanyl and alfentanyl. Older
      patients who decide to accept dialysis treatment contend with all the usual end
      of life issues of older people. They have an additional option, denied to the
      rest of us, of dialysis withdrawal; this effectively allows them to die at a time
      of their choosing.

PMID- 21949924
TI  - Medicine for the elderly symposium.

PMID- 21949925
TI  - Chronic inflammatory states: their relationship to cancer prognosis and symptoms.
AB  - A chronic inflammatory state (CIS) commonly accompanies advanced cancers.
      Elements of a CIS include aberrant immune system activity and changes in
      hypothalamic-neuroendocrine control mechanisms. The end result is stimulation of
      tumour growth and metastases. In addition to tumour stimulation, cancer symptoms
      may be enhanced. While for most symptoms correlation with a CIS remains tenuous,
      clearly a CIS is linked to the aetiology of the cancer anorexia-cachexia
      syndrome. To date clinical studies aimed at a CIS are modest, but the increased
      understanding of the partnership of a CIS, cancer progression and anorexia
      cachexia must lead to targeting a CIS in concert with conventional efforts to
      directly destroy tumour tissue.

PMID- 21949926
TI  - Palliative care symposium: promoting joint palliative care.

PMID- 21949927
TI  - Robert Garrett, Tasmanian penal colony surgeon: alcoholism, medical misadventure
      and the penal colony of Sarah Island.
AB  - Robert Garrett emigrated from Scotland to Van Diemen's Land (now Tasmania) in
      1822. Within a few months of arrival he was posted to the barbaric penal colony
      in Macquarie Harbour, known as Sarah Island. His descent into alcoholism, medical
      misadventure and premature death were related to his largely unsupported
      professional environment and were, in many respects, typical of those subjected
      to this experience.

PMID- 21949928
TI  - The use of lithotomy by missionary surgeons in nineteenth-century China.
AB  - Modern medicine in China owes its origins to Anglo-American medical missionaries
      who introduced Western medicine into China in the early nineteenth century. In
      1835 the first medical missionary to China, the Reverend Dr Peter Parker, founded
      the Canton Ophthalmic Hospital where he pioneered lithotomy and other surgical
      operations for Chinese patients. This paper chronicles the  subsequent
      development of surgery for bladder stones at that institution by Dr Parker, Dr
      John Kerr and their successors. Modifications of technique and improvisations by
      these dedicated practitioners under less-than-optimal conditions and in an
      unfamiliar population, provide a unique and interesting insight into medicine of
      the time as practiced in China.

PMID- 21949929
TI  - Dr William Wilson Ingram (1888-1982): doctor-soldier, physician and Antarctic
      expeditioner.
AB  - Dr William Wilson Ingram (1888-1982), a Scottish-born physician, contributed
      significantly to the health and heritage of Australia, his adopted land. Born on
      Speyside and educated in Aberdeen, he was a doctor-soldier in two World Wars and
      decorated with the Military Cross. Ingram was a Foundation Fellow (1938) of the
      Royal Australasian College of Physicians and established one of the first
      specialist diabetic clinics in Australia, in Sydney in 1928. As an arachnologist,
      he published clinical descriptions of both surviving and fatal cases of
      envenomation by the Sydney funnel web spider, Atrax robustus. He founded the
      Kolling Institute of Medical Research at the Royal North Shore Hospital in Sydney
      where for two generations he was a leader in both undergraduate and postgraduate
      medical education. The international significance of his life's work relates to
      his service as the medical officer and biologist on the two British, Australian
      and New Zealand Antarctic Research Expeditions (BANZARE) of 1929-1931, for which
      service he was awarded the Polar Medal and subsequent Clasp. Those expeditions
      secured, for the British Crown, what was to become the Australian Antarctic
      Territory, ceded to Australia by a British Order in Council of 24 August 1936.
      Sir Douglas Mawson, polar expeditioner and the leader of BANZARE, described
      Ingram as 'an ideal medical officer', one who in addition to his clinical skills
      and judgement, manifested courage and 'physical endurance and a full measure of
      camaraderie'. Ingram has no published obituary or biography. This precis records
      some details of his extraordinary life.

PMID- 21949930
TI  - A Venetian edition of Avicenna's works owned by Lonicer: part 2.

PMID- 21949931
TI  - Functional neurological symptoms.

PMID- 21949932
TI  - South East Scotland experience of HIV testing in patients newly diagnosed with
      lymphoma.

PMID- 21949933
TI  - The routine use of flumazenil infusion following percutaneous endoscopic
      gastrostomy placement to reduce early post-procedure mortality.

PMID- 21949934
TI  - Physician involvement enhances coding accuracy.

PMID- 21949940
TI  - A fluorescence aptasensor based on DNA charge transport for sensitive protein
      detection in serum.
AB  - A novel fluorescence aptasensor based on DNA charge transport for sensitive
      protein detection has been developed. A 15nt DNA aptamer against thrombin was
      used as a model system. The aptamer was integrated into a double strand DNA
      (dsDNA) that was labeled with a hole injector, naphthalimide (NI), and a
      fluorophore, Alexa532, at its two ends. After irradiation by UV light, the
      fluorescence of Alexa532 was bleached due to the oxidization of Alexa532 by the
      positive charge transported from naphthalimide through the dsDNA. In the presence
      of thrombin, the binding of thrombin to the aptamer resulted in the unwinding of
      the dsDNA into ssDNA, which led to the blocking of charge transfer and the strong
      fluorescence emission of Alexa532. By monitoring the fluorescence signal change,
      we were able to detect thrombin in homogeneous solutions with high selectivity
      and high sensitivity down to 1.2 pM. Moreover, as DNA charge transfer is
      resistant to interferences from biological contexts, the aptasensor can be used
      directly in undiluted serum with similar sensitivity as that in buffer. This new
      sensing strategy is expected to promote the exploitation of aptamer-based
      biosensors for protein assays in complex biological matrixes.

PMID- 21949941
TI  - Analysis of flavonoids by capillary zone electrophoresis with electrokinetic
      supercharging.
AB  - On-line concentration via Electrokinetic Supercharging (EKS) was used to enhance
      the sensitivity of the capillary electrophoretic separation of the four
      flavonoids naringenin, hesperetin, naringin and hesperidin. Separation
      conditions, including the background electrolyte pH and concentration, the length
      and choice of terminator and the electrokinetic injection time were optimized.
      The optimum conditions were: a background electrolyte of 30 mM sodium tetraborate
      (pH 9.5) containing 5% (v/v) of methanol, electrokinetic injection of the sample
      (130 s, -10 kV) followed by hydrodynamic injecting of 100 mM 2
      (cyclohexylamino)ethanesulfonic acid (CHES) (17 s, 0.5 psi) as terminator, and
      separation with -20 kV. Under these conditions the four flavonoids could be
      separated with a sample-to-sample time of 15 min and detection limits from 2.0 to
      6.8 ng mL(-1). When compared to a conventional hydrodynamic injection the
      sensitivity was enhanced between 824 and 1515 times which is 7.6-16 times higher
      than other CE methods for the on-line concentration of flavonoids. The
      applicability of the developed method was demonstrated by the detection of the
      four flavonoids in an aqueous extract of Clematis hexapetala pall.

PMID- 21949942
TI  - Prologue: extending study of the visual in the history of sport.
AB  - This paper highlights the value of images and materiality associated with sport
      in the past, and explores the range of sociocultural practices associated with
      them. It provides a critique of the neglect of such sources by many historians
      and notes that interest is now substantially growing in visuality and visual
      material. It emphasises the huge breadth and depth of sports-related evidence
      that can now be accessed, from stamps to stadiums and from posters to sports
      paraphernalia. It then examines the multiplicity of methodologies that can
      potentially be used to exploit the visual, its sites of production and sites of
      reception and seeing.

PMID- 21949943
TI  - Imaging sport at the Grosvenor School of Modern Art (1929-37).
AB  - The mass popularity of sport in Britain during the inter-war years was a source
      of fascination and inspiration for a group of artists working at the Grosvenor
      School of Modern Art in London. Although largely neglected by their
      contemporaries, sport was embraced by Grosvenor School artists as a means to
      engage with both modernity and tradition within contemporary British culture.
      This essay examines one work, Cyril Power's 1930 linocut print, 'The Eight', as a
      case study to investigate the interrelationship between two cultural activities
      frequently regarded as at opposing ends of the cultural spectrum: art and sport.
      By simultaneously drawing upon a rich heritage of visual culture conventions and
      deploying new media and methods to represent the excitement, dynamism and sheer
      energy of sport, Power's work offers an insight into how visual culture can
      engage with, and enhance, our understanding of contemporary debates and practices
      in both fields of activity.

PMID- 21949944
TI  - Reading photographic portraits of Australian women cyclists in the 1890s: from
      costume and cycle choices to constructions of feminine identity.
AB  - During the 1890s, in Australia and around the world, there was a convergence of
      the cycle, the camera and women. With the advent of the revolutionary safety
      bicycle, cycling had become a craze. At the same time, photographic technology
      had undergone changes that meant photographs were cheaper and more accessible.
      Women became avid consumers of both these new technologies; they became cyclists
      in unprecedented numbers for the first time, and they also became the popular
      subjects, and proud owners, of photographic portraits. These two trends
      converged, resulting in a proliferation of photographic portraits of women
      cyclists, many of which were published in newspapers and magazines. These bicycle
      portraits have now become a rich source for historians. More than just visually
      interesting artefacts, these photographic depictions of the Australian woman
      cyclist are important windows into the history of Australian women's cycling in
      the last decade of the nineteenth century. Bicycle portraits provide significant
      insights into the study of Australian women cyclists, from historical detail
      ranging from costume, bicycle and cycling activity choices to more complex
      understandings of the expression of feminine identity among Australian women
      cyclists in the 1890s.

PMID- 21949945
TI  - "We make a big effort to bring out the ladies": visual representations of women
      in the modern American stadium.
AB  - Modern stadiums were constructed across the United States in the 1960s and 1970s,
      usually to replace old baseball parks that were run-down, inaccessible by
      automobile, and located near African American neighbourhoods. Sports promoters
      coveted affluent, white, consumption-oriented customers who had recently moved to
      the suburbs. To attract these customers, promoters attempted to imaginatively
      reconstitute stadium space - from urban, old, dirty, rambunctious, masculine
      places to suburban, new, clean, orderly, female-friendly spaces. The attraction
      of women - as signifiers of an affluent and domesticated postwar social order -
      was central to this strategy. Visual representations of women in new stadium
      spaces were essential to the imaginative reconfiguration and modernisation of
      stadium space. This essay examines their use, particularly in the Houston
      Astrodome. Stadium publications and local newspapers used photographs and
      illustrations of women to conceptually reinvent the stadium, extending a
      distinctively post-war, modern ideology privileging comfort, consumption and
      respectable behaviour into stadium space.

PMID- 21949946
TI  - Liberation and containment: re-visualising the eugenic and evolutionary ideal of
      the "Fizkul'turnitsa" in 1944.
AB  - In July 1944 cross-country races and parades of physical culturists were
      prominently used to celebrate Soviet liberation from German occupation. While
      journalistic accounts stressed the manly health and vigour of the victorious Red
      Army, press photographs in Pravda and Red Sport, and Aleksandr Deneika's
      monumental painting 'Liberation', emphasised images of the young female physical
      culturist. This essay explores what a contextualised analysis of these images may
      have to tell historians about the connections between women, physical culture and
      liberation being projected. The argument suggests that, on one level, the images
      straightforwardly symbolised and celebrated the liberation of the Soviet
      'Motherland'. On another, more complex level, the images represented a
      particularly nuanced notion of constricted liberation for Soviet women deriving
      from 1920s eugenic and evolutionary discourse, inscribed into the contemporary
      imperative for engagement with physical culture as a necessary stage of healthful
      body discipline on the path to hygienic and successful motherhood.

PMID- 21949947
TI  - Seeing your way to health: the visual pedagogy of Bess Mensendieck's physical
      culture system.
AB  - This essay examines the images and looking practices central to Bess M.
      Mensendieck's (c.1866-1959) 'functional exercise' system, as documented in
      physical culture treatises published in Germany and the United States between
      1906 and 1937. Believing that muscular realignment could not occur without seeing
      how the body worked, Mensendieck taught adult non-athletes to see skeletal
      alignment and muscular movement in their own and others' bodies. Three levels of
      looking practices are examined: didactic sequences; penetrating inspection and
      appreciation of physiological structures; and ideokinetic visual metaphors for
      guiding movement. With these techniques, Mensendieck's work bridged the body
      cultures of German Nacktkultur (nudism), American labour efficiency and the
      emerging physical education profession. This case study demonstrates how sport
      historians could expand their analyses to include practices of looking as well as
      questions of visual representation.

PMID- 21949948
TI  - Gentrification in black and white: the racial impact of public housing demolition
      in American cities.
AB  - The gentrification that has transformed high-poverty neighbourhoods in US cities
      since the mid 1990s has been characterised by high levels of state reinvestment.
      Prominent among public-sector interventions has been the demolition of public
      housing and in some cases multimillion dollar redevelopment efforts. In this
      paper, the racial dimension of state-supported gentrification in large US cities
      is examined by looking at the direct and indirect displacement induced by public
      housing transformation. The data show a clear tendency towards the demolition of
      public housing projects with disproportionately high African American occupancy.
      The pattern of indirect displacement is more varied; public housing
      transformation has produced a number of paths of neighbourhood change. The most
      common, however, involve significant reductions in poverty, sometimes associated
      with Black to White racial turnover and sometimes not. The findings underscore
      the central importance of race in understanding the dynamics of gentrification in
      US cities.

PMID- 21949949
TI  - Football and post-war reintegration: exploring the role of sport in DDR processes
      in Sierra Leone.
AB  - Growing enthusiasm for 'Sport for development and peace' (SDP) projects around
      the world has created a much greater interest among critical scholars seeking to
      interrogate potential gains, extant limitations and challenges of using sport to
      advance 'development' and 'peace' in Africa. Despite this interest, the role of
      sport in post-conflict peace building remains poorly understood. Since peace
      building, as a field of study, lends itself to practical approaches that seek to
      address underlying sources of violent conflict, it is surprising that it has
      neglected to take an interest in sport, especially its grassroots models. In
      Africa, football (soccer) in particular has a strong appeal because of its
      popularity and ability to mobilise individuals and communities. Through a case
      study on Sierra Leone, this paper focuses on sports in a particularly prominent
      post-civil war UN intervention-the disarmament, demobilisation and reintegration
      (DDR) process-to determine how ex-youth combatants, camp administrators and
      caregivers perceive the role and significance of sporting activities in interim
      care centres (ICCS) or DDR camps. It argues that sporting experiences in ddr
      processes are fruitful microcosms for understanding nuanced forms of violence and
      healing among youth combatants during their reintegration process.

PMID- 21949950
TI  - Preventive HIV/AIDS education through physical education: reflections from
      Zambia.
AB  - Governments, UN agencies and international and local NGOs have mounted a
      concerted effort to remobilise sport as a vehicle for broad, sustainable social
      development. This resonates with the call for sport to be a key component in
      national and international development objectives. Missing in these efforts is an
      explicit focus on physical education within state schools, which still enroll
      most children in the global South. This article focuses on research into one of
      the few instances where physical education within the national curriculum is
      being revitalised as part of the growing interest in leveraging the appeal of
      sport and play as means to address social development challenges such as
      HIV/AIDS. It examines the response to the Zambian government's 2006 Declaration
      of Mandatory Physical Education (with a preventive education focus on HIV/AIDS)
      by personnel charged with its implementation and illustrates weaknesses within
      the education sector. The use of policy instruments such as decrees/mandates
      helps ensure the mainstreaming of physical education in development. However, the
      urgency required to respond to new mandates, particularly those sanctioned by the
      highest levels of government, can result in critical pieces of the puzzle being
      ignored, thereby undermining the potential of physical education (and sport)
      within development.

PMID- 21949951
TI  - Can health care information technology save babies?
AB  - Electronic medical records (EMRs) facilitate fast and accurate access to patient
      records, which could improve diagnosis and patient monitoring. Using a 12-year
      county-level panel, we find that a 10 percent increase in births that occur in
      hospitals with EMRs reduces neonatal mortality by 16 deaths per 100,000 live
      births. This is driven by a reduction of deaths from conditions requiring careful
      monitoring. We also find a strong decrease in mortality when we instrument for
      EMR adoption using variation in state medical privacy laws. Rough cost
      effectiveness calculations suggest that EMRs are associated with a cost of
      $531,000 per baby's life saved.

PMID- 21949952
TI  - [Conclusions of the 19th Congress held in Milan on May 21, 2011].

PMID- 21949954
TI  - The individual and program impacts of eliminating Medicaid dental benefits in the
      Oregon Health Plan.

PMID- 21949955
TI  - Special issue: Behavioral Economics and Health Annual Symposium.
AB  - The application of behavioral economics to health and health care has captured
      the imagination of policymakers across the political spectrum. The idea is that
      many people are irrational in predictable ways, and that this both contributes to
      unhealthy behaviors like smoking and holds one of the keys to changing those
      behaviors. Because health care costs continue to increase, and a substantial
      portion of costs are incurred because of unhealthy behaviors, employers and
      insurers have great interest in using financial incentives to change behaviors.
      However, it is in the details that complexity and controversies emerge. Who
      should the targets be, and what outcomes should be rewarded? How should
      incentives be structured, to maximize their effectiveness and minimize unintended
      consequences? In what situations should we be intervening to affect decisions by
      people who may prefer to be obese or to smoke, and in what situations should we
      accept their preferences? To begin to answer these questions, the Penn-CMU Roybal
      P30 Center on Behavioral Economics and Health held its first annual Behavioral
      Economics and Health Symposium on March 24-25, 2011 with support from the Robert
      Wood Johnson Foundation. The symposium drew more than 50 researchers, scholars,
      and health professionals from a variety of disciplines, including medicine,
      public health, economics, law, management, marketing, and psychology. They heard
      perspectives on behavioral economics from public and private funders, the CEO of
      the University of Pennsylvania Health System, and the CEO of stickK.com, a start
      up company that uses online, voluntary commitment contracts to help people
      achieve their goals. Participants formed eight working groups to review the
      current state-of-the-art in a variety of clinical contexts and to consider how
      behavioral economics could inform a research agenda to improve health. This Issue
      Brief summarizes the findings of these working groups and the symposium.

PMID- 21949956
TI  - The link between intimate partner violence, substance abuse and mental health in
      California.
AB  - This policy brief presents findings on the linkages between intimate partner
      violence (IPV), emotional health and substance use among adults ages 18-65 in
      California. Among the 3.5 million Californians who have ever been victimized by
      IPV as adults, over half a million report serious psychological distress (SPD) in
      the past year. Almost half of all adult IPV victims indicate that their partner
      was under the influence of alcohol or other drugs during the most recent
      incident. Two-fifths of adult IPV victims report past-year binge drinking and 7%
      report daily or weekly binge drinking. One in three IPV victims expressed a need
      for mental health, alcohol or other drug (AOD) services and almost one-fourth
      used mental health or AOD services during the past year. These disturbing
      findings can aid strategies to identify, intervene with and assist IPV victims
      who experience emotional and/or substance use problems.

PMID- 21949957
TI  - The impact of health care reform on California's children in immigrant families.
AB  - The Patient Protection and Affordable Care Act of 2010 (ACA) restricts its health
      insurance expansions in ways that exclude many uninsured children in California
      who are immigrants or have immigrant parents. These exclusions directly limit
      coverage options for noncitizen children. And immigrant parents, potentially
      misinterpreting eligibility requirements for these new programs, may not enroll
      their citizen children. Using the 2007 California Health Interview Survey (CHIS
      2007), this policy brief estimates that of the 1.08 million children in
      California who were uninsured all or part of the year, between 180,000 to 220,000
      will be excluded from the health care reform expansions due to the combined
      direct and potential indirect effects of these exclusions. This "left-out" group
      comprises between 17% and 20% of all uninsured children in California. In light
      of these exclusions, California's community clinics and public hospitals could
      continue to serve a significant number of uninsured immigrant children even after
      full implementation of ACA.

PMID- 21949958
TI  - [My technique: left ventricle formation in ischemic cardiomyopathy].

PMID- 21949959
TI  - [thoraco-abdominal aorta replacement following descending aorta replacement].

PMID- 21949960
TI  - A story of health education in South Africa.

PMID- 21949961
TI  - The scientific writings of Tom Bothwell and his contribution to iron metabolism.

PMID- 21949962
TI  - Hepatocellular carcinoma: prevention by the first anti-cancer vaccine and other
      means.

PMID- 21949963
TI  - Damaged goods: return to sender. A review of the historical medical records of
      repatriated Chinese miners.
AB  - After the Anglo-Boer (South African) War (1899-1902), there was a shortage of
      unskilled labor on the South African gold mines. Chinese men were imported to
      make up for the deficit. This article reviews the records of indentured Chinese
      mine workers examined for repatriation in 1905. The records tell of high
      proportions of social disorders, respiratory diseases, musculoskeletal disorders,
      opium addiction, and injury. These reflect the social and physical conditions to
      which these men were exposed in the mines.

PMID- 21949964
TI  - Enquiries into health and safety in South African mines in the 20th century: what
      did they have to say about occupational lung disease?

PMID- 21949965
TI  - [Imaging diagnosis. Q & A. Mycotic aortic aneurysm].

PMID- 21949966
TI  - [A monologue by a referee of academic reports. (2) Organization of a report].

PMID- 21949967
TI  - International Leaders Summit: using dialogue to Center the Conversation on the
      Education of Deaf Children and Youth in the 21st century.
AB  - Om July 18, 2010, the eve of the 21st International Congress on the Education of
      the Deaf (ICED 2010), the International Leaders Summit was held at the Center for
      Dialogue at Simon Fraser University, Vancouver, Canada. A total of 120 world
      leaders from 32 countries participated. Presenters, including students, led the
      conversation on current perspectives, teacher preparation, worldwide resources,
      and major issues affecting the education of d/Deaf and hard of hearing infants,
      children, and youth. Summit participants recognized that advances in detection,
      early intervention, and technology present challenges in meeting the needs of a
      student population more diverse than at any other stage in history. While it was
      acknowledged that needs differ in various parts of the world, there was a
      consensus that change is required to prepare students to handle challenges in the
      21st century.

PMID- 21949968
TI  - Educational programs for deaf students.

PMID- 21949969
TI  - University and college programs for personnel in deafness.

PMID- 21949970
TI  - Programs for deaf-blind children and adults.

PMID- 21949971
TI  - Advocacy, support and rehabilitation programs.

PMID- 21949972
TI  - Research on deafness.

PMID- 21949974
TI  - Pathways of lymph and tissue fluid flow during intermittent pneumatic massage of
      lower limbs with obstructive lymphedema.
AB  - Questions remain on the use of sequential pneumatic compression including where
      does the fluid flow to and whether fluid can be moved to the non-swollen tissues
      of the hypogastrium and gluteal region? During pneumatic massage of the limb, we
      studied pathways of lymph and mobile tissue fluid flow using lymphoscintigraphy:
      a) from the calf and thigh across the inguinal region to the healthy non-swollen
      tissues of the hypogastrium and b) in the hypogastrium to the lateral and upper
      abdominal quadrants. To examine if there was effective fluid flow during
      pneumatic massage, plethysmographic flow measurements were also carried out. We
      demonstrated that: (i) pneumatic compression moved isotope in lymph remaining in
      functioning lymphatics and in tissue fluid in the interstitial space toward the
      inguinal region and femoral channel, (ii) there was no isotope crossing the
      inguinal crease or moving to the gluteal area, and (iii) isotope injected
      intradermally in the hypogastrium did not spread during manual massage to the
      upper and contralateral abdominal quadrants. In conclusion, intermittent
      pneumatic compression is effective in pushing mobile tissue fluid and relocating
      large fluid volumes toward the groin. However, the question that still remains is
      how to facilitate further flow toward the non-swollen tissues and thereby
      increase local absorption of fluid.

PMID- 21949973
TI  - Monocytes can be induced to express lymphatic phenotypes.
AB  - Although it has been recently shown that monocytes can transdifferentiate into
      blood vascular endothelial cells which are involved in angiogenesis, little
      attention has been paid to their potential to transdifferentiate into lymphatic
      endothelial cells. Therefore, we examined this question in our study. We first
      stimulated monocytes with either fibronectin (FN), VEGF-C, TNF-alpha, LPS, or IL
      3 for 24h. Then we examined the expression of several markers of lymphatic
      endothelium and found that the monocytes expressed specific lymphatic endothelial
      markers, LYVE-1, Podoplanin, and Prox-1, but not common endothelial markers vWF
      or eNOS. Next, monocytes were incubated in endothelial growth medium with FN and
      VEGF-C for 6d. These monocytes were also found to express LYVE-1, Podoplanin and
      Prox-1, but not vWF or eNOS. Our results indicate that monocytes in vitro can be
      easily induced to present lymphatic phenotypes in an inflammatory environment.

PMID- 21949975
TI  - Changes in quality of life of patients with lymphedema after lymphatic vessel
      transplantation.
AB  - There are multiple treatment options for patients with chronic lymphedema, and
      one successful approach is lymph vessel transplantation. As quality of life
      assessments are frequently not utilized in standard treatment regimes, we
      investigated the change in quality of life for patients with chronic lymphedema
      (total = 212) who had undergone lymphatic vessel transplantation and conservative
      therapy for at least 6 months prior to operation. Quality of life was assessed by
      a modified standard questionnaire examining the physiological and psychological
      status of the patients. Results document a significant improvement in quality of
      life and underscore success of autologous lymphatic vessel transplantation as a
      therapy for lymphedema.

PMID- 21949976
TI  - Measurement of lymphedema using ultrasonography with the compression method.
AB  - Lymphedema is swelling of soft tissues by accumulation of lymphatic fluid due to
      failure of the lymphatic drainage system. Although most measures for lymphedema
      focus on change of volume or size of the extremity, the physical properties of
      the tissue such as resistance to compression are also of clinical importance
      because they affect the quality of life of lymphedema patients. In this study, we
      aimed to compare the thickness and resistance to compression of the skin and
      subcutis between the affected and unaffected arms of patients with lymphedema by
      using ultrasonography together with the compression technique, and we also
      investigated the factors that have an influence on the results. Thirty-nine
      patients with post-mastectomy lymphedema participated in this study. All
      ultrasonographically-assessed thicknesses of skin and subcutaneous tissue in
      affected upper arms and forearms were significantly larger than the contralateral
      (p < 0.05) while all resistances to compression values were significantly lower
      (p < 0.05). These results suggest that measuring the resistance to compression
      and thickness using the compression method with ultrasonography may be a valuable
      tool for evaluating lymphedema after breast cancer surgery.

PMID- 21949977
TI  - A modified rat model for cannulation and collection of thoracic duct lymph.
AB  - Difficulty in collecting lymph samples in small animals has impeded studies on
      lymphatic function and lymph composition. Here we report a simple and effective
      modified rat model for thoracic duct lymph drainage where animals remain in full
      consciousness and have free movement and access to water and food over 12 hours.
      The operative procedure required approximately 30 minutes to perform. Mean lymph
      drainage was 0.71 +/- 0.33 ml/h, and protein concentration did not change
      significantly (mean 37 +/- 2.59 mg/ml) over the 12 hours. However, the number of
      lymphocytes fluctuated widely between 0.08 +/- 0.03 x 10(6)/ml and 12.17 +/- 6.58
      x 10(6)/ml. This modified animal model of thoracic duct lymph collection avoids
      influences of lipid intake, general anesthesia, or limited activity of animals on
      experimental outcomes, and therefore more accurately reflects lymph flow and
      composition under normal physiological conditions.

PMID- 21949978
TI  - Conference attendance and networking can be your wisest investment.

PMID- 21949979
TI  - A statewide multiagency intervention model for empowering schools to improve
      indoor environmental quality.
AB  - A large population of children and adults is potentially exposed to indoor
      environmental quality (IEQ) hazards in schools. Those with asthma are
      particularly at risk because IEQ-related hazards in school buildings can trigger
      asthma episodes. A multiagency consortium created and led by the Connecticut
      Department of Public Health has successfully implemented and continues to sustain
      the U.S. Environmental Protection Agency's (U.S. EPA's) Tools for Schools (TfS)
      program in the majority of Connecticut public schools. TfS is an action kit and
      program promoting a low-cost, problem-solving team approach to preventing IEQ
      hazards or improving IEQ. One key to the consortium's success is the array of
      services it provides to schools, including aggressive outreach and specialized
      training and consultation. The consortium is also a platform for launching other
      school IEQ initiatives. The authors present and analyze the consortium model and
      their efforts at evaluating the impact of TfS in Connecticut.

PMID- 21949980
TI  - Low-level groundwater arsenic exposure impacts cognition: a project FRONTIER
      study.
AB  - Arsenic is a ubiquitous environmental toxin with known neurological consequences.
      Few studies, however, have investigated groundwater arsenic concentrations and
      cognition among adults and elders. In the study described in this article, the
      authors examined the potential link between cognitive functioning and low
      concentrations of arsenic in drinking water. Arsenic concentrations were
      estimated by the Geographic Information System approach (GIS-arsenic) for 299
      rural-dwelling adults and elders. Cognition was assessed with Folstein Mini
      Mental State Examination (MMSE). Those in the relatively high GIS-arsenic
      exposure (> 10.0 microg/L) group had significantly lower MMSE scores than those
      in the low GIS-arsenic exposure (< or = 10.0 microg/L) group (p < .03). The
      number of years of education was significantly lower in those in the high GIS
      arsenic group(s) than in those in the low GIS-arsenic group (p < .05). These
      results suggest that poorer cognitive functioning and lower education levels were
      associated with higher (though still low-level) GIS-arsenic levels in this rural
      adult cohort.

PMID- 21949981
TI  - Solid waste management problems in secondary schools in Ibadan, Nigeria.
AB  - Inappropriate solid waste management practices in schools in less-developed
      countries, particularly in major urban communities, constitute one of the major
      factors leading to declining environmental health conditions. The objective of
      the authors' descriptive, cross-sectional study was to assess solid waste
      management problems in selected urban schools in Ibadan, Nigeria. Eight secondary
      schools with average pupil populations not less than 500 per school were selected
      randomly. Four hundred questionnaires (50 per school) were administered. In
      addition, an observational checklist was used to assess the physical environment.
      Paper and plastics were the most frequently generated wastes. Common methods of
      solid waste disposal reported were use of dustbins for collection and open
      burning. Major problems perceived with current refuse disposal methods by the
      study students were odors, pest infestation, and spillages. Littering and
      spillages of solid waste were also common features reported. Data suggested
      inadequate waste management facilities and practices in study schools. The lack
      of refuse bins may have contributed to waste spillages and the burning practices.
      Odors may have arisen from both the decay of overstored organic waste rich in
      moisture and emissions from refuse burning. This scenario poses a community
      environmental health nuisance and may compromise school environmental quality.

PMID- 21949982
TI  - New food safety training opportunity using cutting edge technology!

PMID- 21949983
TI  - The centrality of environmental health to the communities we serve case study:
      Joplin, Missouri.

PMID- 21949984
TI  - Federal pre-emption under the Food, Drug & Cosmetic Act from Medtronic, Inc. v.
      Lohr; Pliva. Inc. v. Mensing.

PMID- 21949985
TI  - [Evaluation of the audiological characteristics of 3251 cases who failed the
      newborn hearing screening in Guangzhou].
AB  - OBJECTIVE: To analyze the audiological characteristics of the cases who failed
      the newborn hearing screening under the two hearing screening programs (OAE and
      AABR) in two different screening population(with or without high-risk of hearing
      loss). METHOD: Three thousand two hundred and fifty-one babies (6502 ears) who
      failed the hearing screening twice or more and then failed in the audiological
      evaluation are included in the research. The cases were divided into two groups
      by the time accepting the screening, < 6 (2683 cases) months or > or = 6 months
      (568 cases), and then analyze the effect of age on the audiological
      characteristics. Compare the sensitivity and specificity of different hearing
      screening programs, OAE or AABR. Evaluate the audiological characteristics
      between the groups with or without the high-risk factors of hearing loss. Total
      of them were performed detailed audiological evaluation including in ABR, DPOAE,
      acoustic immittance, and some of them accepted ASSR test and computer tomography.
      RESULT: 85.30% to 86.54% infants accepted initial screening in Guangzhou city,
      and less than 64. 10% infants underwent rescreening. 0.0282% or 0.0220% infants
      needed immediately early intervention. The group without high-risk factors was
      less likely to suffer from mild to profound hearing loss than those with high
      risk factors. According to different hearing screening programs, more cases
      passed the OAE hearing screening and more cases were diagnosed profound hearing
      loss under AABR screening. CONCLUSION: AABR screening technology is better than
      OAE screening. The target population is the infants with risk factors, so
      perinatal history record is very important. The percentage of population who need
      immediately early intervention is more than 0.0282%-0.0220%.

PMID- 21949986
TI  - [Validation of rehabilitation and relative analysis for prelingually deafened
      children with cochlear implant].
AB  - OBJECTIVE: To study the validation of rehabilitation for prelingually deafened
      children with cochlear implant and explore the relationship between the age and
      the rehabilitation effectiveness, and the change of the effectiveness over time.
      METHOD: Thirty-six investigated prelingually deafened children with cochlear
      implant were divided into two groups (< or = 3 years old and > 3-6 years old)
      according to the age of receiving the operation. The validation of rehabilitation
      was assessed at different times (3 months, 6 months, 9 months, 12 months) after
      the devices began to work. RESULT: The longer the rehabilitation, the better the
      validation (P < 0.05). The speed of the younger group (less than 3 years old) is
      faster than the other group by the time (P < 0.05) in the auditory perception and
      speech. There is no significant difference between the two groups in
      intelligence. CONCLUSION: Prelingually deafened children should receive the
      cochlear implant as young as possible and take more rehabilitation training after
      the operation.

PMID- 21949987
TI  - [The development of preverbal communication skills in Chinese deaf children with
      cochlear implants].
AB  - OBJECTIVE: To evaluate preverbal communication skills in Chinese deaf children
      with cochlear implants, and to provide a basis for designing the habilitation
      program and establish a precursor for outcomes of habilitation. METHOD: Thirty
      children with cochlear implants participated in this study with a mean age of 32
      months. They all had used the cochlear implant system within 12 months with a
      mean of 5. 8 months. All the children were diagnosed with prelingual profound
      hearing loss before cochlear implantation. Tait video analysis was used to
      analyze and assess the preverbal communication skills including turn-taking,
      autonomy, eye contact and auditory awareness. All statistical analyses were
      performed using the SPSS 13.0 statistical software package with a criterion of
      statistical significance set at P < 0.05. RESULT: The skill of turn-taking
      developed quickly within 12 months after cochlear implantation. The vocal turn
      developed in a similar pattern, and the score of gesture turn decreased slowly.
      The skills of autonomy and appropriate eye contact showed small changes over time
      at a lower level. The score of auditory awareness increased gradually after
      surgery. CONCLUSION: Children established a vocal/auditory mode of early
      communicative behavior following cochlear implantation. They preferred to
      communicate with others in a more vocal style. Video analysis is a useful tool to
      assess preverbal communication skills in deaf children with cochlear implants in
      China.

PMID- 21949988
TI  - [Research on the relationship of IgE between adenoid and middle ear effusion in
      children otitis media with effusion cases].
AB  - OBJECTIVE: To study the expression of IgE in recur repeatedly children otitis
      media with effusion (OME), and the relativity of IgE between adenoid and middle
      ear effusion. METHOD: Thirty-five cases diagnosed of OME in our department, were
      enrolled in the research. Thirty-one adenoidal hypertrophy cases were selected as
      control group. Obtained middle ear effusion and adenoid samples from experimental
      group, and obtained adenoid samples from control group. All adenoid samples were
      taken for tissue homogenate. Determination all samples of concentration of IgE by
      ELISA. SPSS 18.0 statistical software was used for all relevant data processing
      and analysis. RESULT: Compared the IgE content between experimental group and
      control group with adenoid samples, IgE content increased significantly in
      experimental group (P < 0.05), and IgE in experimental group of middle ear
      effusion samples were also increased (P < 0.05). The content of IgE in the
      experimental group of middle ear effusion and adenoid assumed straight-line
      correlation, in negative correlation (r = 0.580, P < 0.05). CONCLUSION: The
      occurrence of OME is related to immune factors. Adenoidal hypertrophy may lead to
      local immunity enhancement, may cause middle ear cavity immune system
      abnormality, give rise to recur repeatedly with OME and procrastinate does not
      recover.

PMID- 21949989
TI  - [Mastoidectomy and ventilation tube placement for refractory secretory otitis
      media].
AB  - OBJECTIVE: To study the mastoidectomy and ventilation tube placement for
      refractory secretory otitis media of clinical efficacy and mechanism. METHOD:
      Retrospective analysis of 22 patients (33 ears) in refractory secretory otitis
      media, all patients treated by ventilation tube placement have 3 or more than 3
      times, but not significantly alleviate the symptoms. Mastoid surgery and
      ventilation tube placement were basic surgical management. Tympanic membrane
      ventilation tube was pulled out at 3 to 6 months. RESULT: Twenty-two patients
      perceived improvement of hearing after surgery, ear fullness disappeared;
      tympanic membrane was gray, no significant tympanic membrane mobility is limited;
      33 ears conductive hearing loss, air-bone gap(13.54 +/- 4.86) dB; after 29 ears
      tympanograms showed A-type, 4 ears for C-type, 30 ears appear ipsilateral
      acoustic reflex. CONCLUSION: For 3 or more than 3 times repeated ventilation tube
      insertion, patients more than 2 years of refractory secretory otitis media were
      treated with mastoidectomy and ventilation tube placement, it was satisfied that
      ears lesions were cleaned and expanded middle ear and mastoid air cell volume,
      good drainage of the tympanic membrane ventilation tube.

PMID- 21949990
TI  - [Rapid genetic diagnosis of patients with non-syndromic sensorineural hearing
      loss].
AB  - OBJECTIVE: To evaluate the feasibility of a rapid genetic diagnosis technique in
      molecular genetics study of hearing loss. METHOD: One hundred and ten subjects
      including 54 with moderate to profound non-syndromic sensorineural hearing loss
      were enrolled in this study. All with informed consents. Their peripheral blood
      samples were taken and tested using Hearing Loss Array Kit developed by Capital
      Bio. Nine hot mutation sites from 4 high risk genes were tested each. RESULT: The
      overall positive rate in this cohort was 50.9%, while the positive rate among 54
      hearing loss cases was 59.3%. DNA sequence analysis showed 100% coincident with
      gene chip results. CONCLUSION: This Hearing Loss Array Kit (gene chip) has a high
      positive detection ratio, its characteristics such as rapid high-flux sensitive
      and high specific make it possible and promising in future screening and
      diagnosis in patients with sensorineural hearing loss. Molecular genetic
      diagnosis also has a profound value in deafness prevention.

PMID- 21949991
TI  - [Synergic effect of alprostadil injection and ginaton in treating sudden
      deafness].
AB  - OBJECTIVE: To explore synergic effect of Alprostadil injection and ginaton in
      treating sudden deafness. METHOD: ninety one patients with sudden deafness were
      divided into group A, group B and group C at random; 33 ears of group A were
      treated with 70 mg ginaton by vein, 30 ears of group B were treated with 10
      microg Alprostadil injection by vein, 31 ears of group C were treated with 10
      microg Alprostadil injection and ginaton by vein,once a day, the time of
      treatment is 14 days. RESULT: the effective rate of group A is 60.61%, the
      effective rate of group B is 60.00%, the effective rate of group C is 87.09% the
      treating effect was significantly different in the group A and C (P < 0.05), it
      was significantly different in the group B and C (P < 0.05)). CONCLUSION: It is
      effective for Alprostadil injection and ginaton to treat sudden deafness, and it
      has significantly Synergic effect in treating sudden deafness with Alprostadil
      injection and ginaton.

PMID- 21949992
TI  - [Analysis of prognostic factors for sudden sensorineural hearing loss].
AB  - OBJECTIVE: To analysis the prognostic factors of the sudden sensorineural hearing
      loss (SHL), to predict the prognosis of patient with SHL precisely. METHOD: Two
      hundred and fifty-six cases (280 ears) with SHL were reviewed retrospectively
      during January 2005 to Jun 2009. Possible influence factor was analysis with
      logistic stepwise regression to investigate the correlation with prognosis. All
      verified influence factors was analysis with single-factor analysis of variance.
      RESULT: The prognosis of SHL related to age, the trouble time before treatment,
      vertigo with(or) tinnitus, degree of hearing loss, the patterns of audiogram, but
      not to sex and trouble ear. With increasing of age, the prognosis of SHL becomes
      poor. Especially after 40 years old, the prognosis gets worse. Regarding to the
      relationship between the trouble time before treatment and the prognosis. The
      groups within 9 days have no significant difference (P > 0.05). There are
      significant difference between group of > 3-9 days and > 9-15 days (P < 0.05), >
      9-15 days and > 15 days (P < 0.05). Compared with patients suffer from vertigo or
      (and) tinnitus, patients without vertigo or (and) tinnitus obtain a good result
      (P < 0.05). As for initial hearing threshold, flat (upgrade) subgroup, downgrade
      (upgrade) subgroup, upgrade subgroup and valley-mountain subgroup have no
      significant difference (P > 0.05). However, there are significant difference
      between upgrade subgroup and flat subgroup, upgrade subgroup and all the others.
      Furthermore, comparison with the low,midst, severe and profound hearing loss, the
      prognosis among them is no statistical different. But statistical different
      exists between media and profound subgroup. CONCLUSION: The factor of age, the
      trouble time before treatment, vertigo with (or) tinnitus, degree of hearing
      loss, the patterns of audiogram are correlated with prognosis of SHL. The
      prognosis has a poor tendency with age increasing, especially after 40 years old.
      Good result maybe achieved within 9 visiting days. After that, the recovery rates
      declined obviously. Patients have company complication, such as vertigo or (and)
      tinnitus have poor prognosis. The downgrade subgroup of audiogram has high
      incidence rate although upgrade subgroup has a good prognosis. The level of
      hearing loss before medication is not a simple linear correlation with prognosis.
      Media hearing loss demonstrate the best prognosis. On the contrary, profound
      hearing loss has the worst prognosis. With hearing threshold added, the total
      recovery rates goes down.

PMID- 21949993
TI  - [A preliminary observe of the different age children with unilateral hearing
      loss].
AB  - OBJECTIVE: To observe the effect on children with unilateral hearing loss (UHL).
      METHOD: One hundred and one children with unilateral hearing loss were included
      in this study from October 2008 to December 2009 in Shenzhen Children's Hospital,
      95 of them were investigated on speech recognition abilities, learning abilities
      et al by telephone interviews. RESULT: The intelligence quotient (IQ) including
      full-scale intelligence quotient, verbal intelligence quotient and performance
      intelligence quotient were significantly lower in the severe and profound
      unilateral hearing loss group when compared with school children with bilateral
      normal hearing (P < 0.05). The IQ of moderate to severe hearing loss and
      bilateral normal hearing was not significantly different (P > 0.05). CONCLUSION:
      IQ, speech recognition abilities and learning abilities were affected during
      unilateral hearing loss children, but proper, early intervention can compensate
      the deleterious effects of UHL.

PMID- 21949994
TI  - [A study of the pepsin in the sputum for diagnosis and treatment evaluation of
      laryngopharyngeal reflux].
AB  - OBJECTIVE: To study the value of the pepsin in the sputum for diagnosing and
      evaluating the effectiveness of treatment of laryngopharyngeal reflux. METHOD:
      Thirty-six patients with the symptoms of dry pharynx, globus pharyngeus,
      excessive throat clearing, chronic cough and so on were divided into
      laryngopharyngeal reflux group and chronic laryngitis group by the results of
      therapeutic trial taking proton pump inhibitors for 3 months. The estimation of
      the reflux symptom index (RSI), the reflux finding score (RFS) and the detection
      of pepsin in the sputum were done before and after the treatment. The difference
      between two groups and the value of the pepsin were analyzed. RESULT: There were
      significant decreasing in RSI, RFS and pepsin level (P < 0.01) after the
      treatment in all patients. There were statistical differences between the
      laryngopharyngeal reflux group and the chronic laryngitis group in the changes of
      RSI and pepsin level (P < 0.01). CONCLUSION: Pepsin level in the sputum might be
      used as a objective, effective method for diagnosing and evaluating the
      effectiveness in laryngopharyngeal reflux.

PMID- 21949995
TI  - [Computerized three-dimensional reconstruction of cochlear microstructures].
AB  - OBJECTIVE: To explore an useful and practical method for three-dimensional
      reconstruction of cochlear microstructure. METHOD: A digital image dataset of
      magnified forty times of human cochlear tissue can be get from the serial
      sections of transverse cedukol images of male cadavers temporal bone. Photoshop
      6.0 and Amira 3.0 software were used to deal with the digital image dataset, such
      as image-connecting and image inner-location and three-dimensional reconstruction
      of cochlear and scala media. RESULT: The result of three-dimensional
      reconstruction of the cedukol images represents the anatomy of human cochlear and
      scala media transparently and objectively. CONCLUSION: The three-dimensional
      reconstruction technique used in the study is practical for three-dimensional of
      inner ear microstructure.

PMID- 21949996
TI  - [Surgery for mass at root of the neck--with 26 cases report].
AB  - OBJECTIVE: To investigate the surgical treatment of mass at root of the neck.
      METHOD: Twenty-six cases of mass in root of the neck, 10 benign tumor and 16
      malignancy. All the patients were received surgical treatment with "T" or "L"
      shaped incision, and cleidotomy or remove partial of presternum and
      articulationes sternoclavicularis when necessary. RESULT: All the benign tumor
      were removed completely, 1 case with chylous leakage and 1 case with recurrent
      laryngeal nerve injury after operation. Twelve cases of malignant tumor removed
      completely and 4 cases underwent partially resection. Subclavian vein rupture
      occur in 2 cases during operation, and chylous leakage in 1 case, brachial plexus
      or phrenic nerve injury in 2 cases individually, 1 case with mediastinal
      emphysema and 2 cases with hematoma. Follow up for 1 to more than 5 years. No
      patient died and relapsed in benign group. Six malignant cases survive for 5
      years after operation,4 cases survive for more than 3 years,and 2 patients alive
      for 2 years. And the others were died within 1 year in malignancy group.
      CONCLUSION: Surgery for mass in root of the neck is feasible and with good effect
      for benign mass,and also is a way to treat the malignancy in this region.

PMID- 21949997
TI  - [Endoscope-assisted excision of cystic hygroma in neck].
AB  - OBJECTIVE: To get more cosmetic effect, we explore the feasibility, validity and
      security of endoscope-assisted excision of the cystic hygroma. METHOD: Six
      patients of cystic hygroma accepted endoscope-assisted excision of the cystic
      hygroma in neck, 3 by anterior chest approach alone, 1 by upper incision alone,
      and 2 by combined approach. RESULT: All procedures were successfully done using
      the endoscope -assisted approach. There were no conversion of the operations and
      postoperative complications. All families were satisfied with the cosmetic
      results. CONCLUSION: Endoscope-assisted excision of the cystic hygroma via
      different approaches can be applied effectively, safely and feasibly, allowing
      adequate exposure for dissection, and resulting in a good cosmetic results, and
      would be considered as a newly surgery for these patients.

PMID- 21949998
TI  - [Expression and significance of MTA1 and RECK gene in nasopharyngeal carcinoma].
AB  - OBJECTIVE: To determine the expression of MTA1 and RECK gene in nasopharyngeal
      carcinoma (NPC) and its correlation with clinicopathological features. METHOD: In
      situ hybridization was used to detect the expression of MTA1 and RECK mRNA in 60
      cases of primary NPC (30 cases with, 30 cases without cervical lymph node
      metastasis), 10 cases of metastatic lymph node (MLN) and 20 cases of chronic
      nasopharyngitis tissue (CNT). RESULT: 1) Positive rates of MTA1 mRNA expression
      in CNT, NPC and MLN were 30.0% (6/20), 71.7% (43/60) and 80.0% (8/10),
      respectively. The positive expressions of MTA1 in NPC and MLN were significantly
      higher than in CNT (P<0.05). The MTA1 mRNA expression in NPC with lymph node
      metastasis was significantly higher than in NPC without lymph node metastasis
      (83.3% vs. 60.0%, P<0.05). 2) Positive rates of RECK mRNA expression in CNT, NPC
      and MLN were 85.0% (17/20), 26.7% (16/60) and 30.0% (3/10), respectively. The
      positive expression of RECK in NPC and MLN were significantly lower than in CNT
      (P< 0.05). The RECK mRNA expression in NPC with lymph node metastasis was
      significantly lower than in NPC without lymph node metastasis (13.3% vs. 40.0%,
      P<0.05). 3) Abnormal expression of MTA1 and RECK mRNA in NPC had no correlation
      with gender, age, T-stage and clinical stage (P>0.05), while they had positive
      relationship with lymph node metastasis, tumor recurrence and the post-treatment
      5-year survival periods of NPC (P<0.05). The expression of RECK mRNA was
      negatively correlated with the expression of MTA1 mRNA in NPC (r = - 0.541,
      P<0.05). CONCLUSION: These data suggest that the aberrant expression of MTA1 and
      RECK gene may be involved in the invasion and metastasis of NPC. They may be good
      biomarkers for evaluating the cervical lymph node metastasis, recurrence and
      prognosis of NPC.

PMID- 21949999
TI  - [Expression of programmed cell death 4 protein is closely correlated with
      laryngeal squamous cell carcinomas].
AB  - OBJECTIVE: To study whether programmed cell death 4 (PDCD4) is involved in the
      development and progression of laryngeal squamous cell carcinomas (LSCC). METHOD:
      The expressions of PDCD4 protein were examined by immunohistochemical staining
      and Western blot in LSCC tissues and their surrounding laryngeal normal mucosa
      tissues. RESULT: The positive rate of PDCD4 protein in LSCC was significantly
      lower than that in the laryngeal normal mucosa tissues by immunohistochemical
      staining (P<0.01). No correlation was found between positive expression of PDCD4
      and gender, age, tumor site, TNM stage, but there was significant correlation
      between positive expression of PDCD4 from differentiation grading and lymphatic
      matastasis. Meanwhile,we got the similar results by Western blot (P<0.01).
      CONCLUSION: The low expression of PDCD4 protein is closely related to the
      development and progression of LSCC. PDCD4 might be a novel molecular marker for
      prognosticating metastases and prognosis of LSCC.

PMID- 21950000
TI  - [The depth of CO2 laser cordectomy in T1 glottic carcinoma].
AB  - OBJECTIVE: To evaluate if routine resection of thyroarytenoid muscle (TA) with T1
      glottic carcinoma treated by endoscopic CO2 laser cordectomy is necessary.
      METHOD: A cohort of 57 patients staged as T1 underwent endoscopic CO2 laser
      cordectomy at a single institution was retrospectively analyzed. Seven had Tis,
      47 T1a and 3 T1b; 9 cases were treated with type I or II cordectomies, and 48
      patients underwent type III, IV or V cordectomies, with resection of all or part
      of the TA. All histological slides from the 48 patients were re-examined under
      the light microscope for TA invasion by the pathologist and the surgeon. Survival
      and local control were calculated using the Kaplan-Meier method. RESULT: The
      follow-up period for the 57 patients ranged from 4 to 119 months (mean follow-up
      41.5 months). Among the 4 patients who died, 1 of them was related to the glottis
      carcinoma and 3 others had died of other causes with no evidence of locoregional
      glottic disease. The 5 year overall survival, 5 year disease-specific survival
      and 5 year disease-free survival were 89.1%, 96.3% and 78.1%, respectively. When
      the study ended, 10 (17.5%) local and 1 regional recurrences had been observed.
      Over a total of 57 patients, 5 (8.8%) cases showed TA invasion. Open salvage
      therapy was performed during follow-up. Six patients had partial laryngectomy.
      Four patients had total laryngectomy and one with neck dissection. One patient
      had radical neck dissection because of late regional relapse was proven by
      histopathologic examination. Thus, the larynx was preserved in 93.0% (53/57).
      CONCLUSION: TA invasion found histologically in T1 glottic carcinoma. TA
      resection can be performed conservatively according to an accurate preoperative
      and intraoperative evaluation of macroscopic tumour extension.

PMID- 21950001
TI  - [Comparative study of endoscopic and open thyroidectomy].
AB  - OBJECTIVE: To compare the therapeutic effect between endoscopic thyroidectomy and
      open thyroidectomy. METHOD: One hundred and nine patients were randomly divided
      into two groups. The first group with 52 patients were carried out endoscopic
      thyroidectomy; and the second group with 57 patients was carried out open
      thyroidectomy. Clinical features including operation time, operative blood loss,
      hospitalization and complications were compared between the two groups. RESULT:
      The average operative time was (105.1 +/- 30.2) min in endoscopic group and
      (145.3 +/- 27.4) min in open group (P<0.01); the mean operative blood loss was
      (7.5 +/- 4.2) ml in endoscopic group and (48.6 +/- 18.6) ml in open group
      (P<0.01); the average hospitalization after operation was (4.1 +/- 1.4) days and
      (8.0 +/- 1.9) days (P<0.01), the complication rate was 5.8% in endoscopic group
      and 8.8% in open group (P<0.01). CONCLUSION: Compared to the traditional open
      surgery, endoscopic thyroidectomy is safe and effective,with advantages in terms
      of the aesthetic property,the amount of bleeding and the postoperative
      complications.

PMID- 21950002
TI  - [Clinical analysis of 42 cases with adenoid cystic carcinoma of the nasal
      cavity].
AB  - OBJECTIVE: To study the clinical characters, treatment, outcome and the factors
      affecting long-term treatment results of adenoid cystic carcinoma (ACC) of the
      nasal cavity. METHOD: The clinical data were analyzed retrospectively in 42
      patients with ACC of the nasal cavity treated initially. The characters of
      survival rate, local recurrence and distant metastasis were analyzed using Kaplan
      Meier method. Factors that might be related to the prognosis were analyzed by Log
      rank test. RESULT: The 5-,10-,15-,20-year cumulative overall survival and disease
      free survival rate were 88.1%, 54.4%, 35.4%, 35.4% and 60.0%, 53.1%, 30.2%, 30.2%
      respectively. The 5-,10-,15-,20-year cumulative local control rate were 69.5%,
      62.3%, 49.8%, 49.8% respectively and the cumulative distant metastasis rate were
      22.2%, 25.9%, 34.2%, 34.2% respectively. Clinical T stage was the factor
      affecting local control and survival (P<0.05). There was no difference in
      survival for patients treated by surgery along with sufficient margins, compared
      with patients treated by surgery combined with postoperative radiation. Patients
      treated with preoperative radiation had poorer local control and survival than
      patients treated with postoperative radiation, but there was no statistical
      significance (P>0.05). The most of patients (75%) died of local recurrence at the
      primary site. CONCLUSION: The most frequent site of failure was local recurrence
      at the primary site. Patients with early stage disease are amenable to surgery
      alone with sufficient margins. Surgery combined with high-dose postoperative
      radiation improves the local control and survival in patients with positive
      margins, no sufficient margins or advanced disease (T3 + T4). The most of tumors
      could be reduced remarkably and the radical operation may be performed for the
      patients with unresectable advanced tumors after preoperative radiation.

PMID- 21950003
TI  - [Temperature-controlled radiofrequency-assisted endoscopic tonsillectomy and
      adenoidectomy in children].
AB  - OBJECTIVE: To compare the outcomes of temperature-controlled radiofrequency
      assisted endoscopic tonsillectomy and adenoidectomy (rT + A) and conventional
      tonsillectomy and adenoidectomy (cT + A) in children. METHOD: Forty-seven
      children who were with hypertrophy of both tonsils and adenoid and underwent
      tonsillectomy and adenoidectomy were retrospectively studied. There are 24
      patients underwent rT + A and 23 patients underwent cT+A. Data of surgery time,
      bleeding volume, duration of postoperative pain and duration of postoperative
      pseudomembrane were collected and analysed. Hearing and disease-specific quality
      of-life questionnaire (OSA-18) were analysed. RESULT: Surgery times of rT + A are
      statistically shorter than those of cT + A, bleeding volumes of rT + A are
      significantly less than those of cT + A. There are no differences of the duration
      of postoperative pain and duration of pseudomembrane between these two groups.
      Hearings were increased to normal in all conductive hearing loss patients. OSA-18
      scores were declined significantly in rT + A group than cT + A. CONCLUSION:
      Temperature-controlled radiofrequency-assisted endoscopic operation can reduce
      bleeding volume and shorten surgery time without more pain or injury to patients,
      and the effect is satisfactory.

PMID- 21950004
TI  - [The expressions of alpha-enolase in the nasopharyngeal cancer tissue].
AB  - OBJECTIVE: To study the meaning of expressions of ENO1 in the nasopharyngeal
      cancer tissue. METHOD: By using SP immunohistochemical methods. RESULT: The
      positive expressions for ENO1 were 60.0% in the nasopharyngeal cancer
      tissues,significantly higher than that (27.5%, 11/40) of in inflammatory
      nasopharyngeal mucosa (P<0.05). The positive expression rate of ENO1 protein in
      stage T1 + T2 + T3 was higher than that of in patients with T4 (chi2 = 11.424,
      P<0.05). But there was no significant relationship between expression of ENO1 and
      lymph node metastasis and postradiotherapy distant metastasis (P>0.05).
      CONCLUSION: The results show that ENO1 over expression may play a important role
      in cell proliferation and canceration of nasopharyngeal cancer.

PMID- 21950005
TI  - [Preventing laryngeal anterior commissure adhesion after operation: a study in
      canines].
AB  - OBJECTIVE: To explore the better operational methods by the laser surgery to
      treat diseases involving the laryngeal anterior commissure. It can excise the
      diseases as well as avoid anterior commissure adhesion, laryngostenosis and
      dyspnea after operations. METHOD: Twelve dogs were divided into 4 groups at
      random. There were three dogs in one group. A: excising experimental dog's
      anterior commissure by twice operations, the interval time was two weeks; B:
      excising experimental dog's anterior commissure in one time, at the same time
      suturing the silica gel sheet on the anterior commissure; C: excising
      experimental dog's anterior commissure in one time and then applying MMC on the
      wound of the anterior commissure; D: excising experimental dog's anterior
      commissure in one time, without any treatment. RESULT: All of the dog's surgery
      were completed successfully by laser. Four weeks later, we observed the raw
      surfaces. A: the neonatal membrane covered the wound, inflammatory reaction
      slight, we could not see obvious adhesion in the anterior commissure. B: the
      membrane covered the wound, appearing the dark chronic inflammation, we could see
      the adhesion in the anterior commissure slight. C: the membrane covered the
      wound, edematization, we could see the moderate adhesion in the anterior
      commissure. D: edematization, we could see the adhesion in the anterior
      commissure obviously. Four groups were all appeared hoarsenesses, the most
      slightly in group A, secondly in B and C, the worst in D. The analysis of vocal
      cord length of 4 groups, we used matched-pairs t-test, A, B, C groups' P>0.05,
      the vocal cord length didn't become shorter than before obviously. Group D's
      P<0.01, that meant the vocal cord length became shorter obviously. Between each
      group,we used reiterature-measurement analysis of variance (P<0.05), the change
      of vocal cord length had disparity in different groups. The comparison in two
      groups suggested that group A is the best. B and C are inferior ,but no disparity
      between them. The analysis of glottis area of 4 groups, as the same method above,
      A,B groups' P>0.05, the glottis area didn't shrink than before obviously. C and D
      groups' P<0.05, that meant having statistical significance and glottis area
      shrinked obviously. Between each group, we used reiterature-measurement analysis
      of variance (P>0.05), we could not think that the changes of four groups have
      disparity. CONCLUSION: Excising the experimental dog's anterior commissure by
      laser, compared the 4 different operation methods, group A is the best method. B
      and C are inferior. The results are valuable in clinic when we perform operations
      by laser to treat the disease involving the anterior commissure.

PMID- 21950006
TI  - [The report on scientific-organizational activity of Section of Physiology of
      Branch of Biological Sciences RAS in 2010].

PMID- 21950007
TI  - [The organism tolerance to extreme factors: physiological basis, regulation,
      prediction].
AB  - The modern ideas about organism reactivity and tolerance, approaches to their
      estimation and prediction were observed in the paper. The ionizing radiation used
      as the basic factor, because this factor is the most convenient for the
      experimental investigation and experimental modeling of the different factors.
      The individual radiotolerance were observed as the reflection and the component
      of the organism general nonspecific tolerance. The enough voluminous of different
      physical factors combined influences were investigated, their reciprocally
      modified influences to the organism tolerance were estimated. The investigation
      of mammalian organism tolerance types and tactics of adaptation to the repeated
      influence of the stress-factors opens the new way to their estimation and
      prediction. The enough simple and reliable method of the individual tolerance (in
      particular, with used of the hormonal regulation system indices) were devised.
      This method is more effective than methods devised earlier.

PMID- 21950008
TI  - [Displays of individually-typological features of animals and the person at a
      choice of strategy of goal-direction behavior].
AB  - In work the hypothesis according to which different forms of goal-directed
      behavior develop depending on the basis of the undervaluation/supervaluation of
      reinforcement by brain abilities at the conditions of its achievement
      uncertainty. From these positions such opposite biological characteristics of the
      subject, as impulsiveness/self-control, care/propensity to risk on which basis
      there are individually typological features in behavior of the person and animals
      are considered. In the article, our experimental data on animals and the persons
      by behavioral techniques and results of last years on research of neural networks
      of animal cortical and subcortical brain structures depending on the strategy in
      choice behavior are also analyzed.

PMID- 21950009
TI  - [Regulation of motor behaviour].
AB  - The review is devoted to analysis of the basic links of motor behavior control
      systems: sensorimotor cortex, cerebellum, a red nucleus and striatum. The
      organization and communications of these structures and their participation in
      learning and memory processes are described. The synaptic neurotransmitter and
      nonsynaptic neuromodulatory systems innervating these structures are also
      described. Hierarchical synaptic networks are formed by GABA and glutamatergic
      systems. The nonsynaptic dopaminergic system innervates both of these structures,
      but carries out a modulatory function. The mesocorticolimbic dopaminergic system
      induces an emotional and motivational state - processes of reinforcement, and
      participates in realization of purposeful behavior. The nigrostriatal
      dopaminergic system, through triggering an endocellular signal and the processes
      ofphosphorylation and dephosphorylation modulates activity ofGABA and
      glutamatergic receptors ofdorsal striatum spiny neurons and adapted
      thalamocortical networks.

PMID- 21950010
TI  - [Immune links in the system organization of behaviour].
AB  - The work is devoted to the research of immune mechanisms in self-control of
      various functional systems of homeostatic and behavioral levels. Distinction of
      immune mechanisms in rats with different prognostic stress-resistance is
      established. Immunization of rats by conjugates of various neuromediators with
      bovine serum albumin selectively changes the animals stress-resistance.
      Participation cytokines in reactions of a brain's separate neurons and their
      interaction with a leading neuromediator - norepinephrine is established.
      Individual changes of pro- and anti-inflammatory cytokines in blood serum are
      shown in rats with different stress-resistance. There are revealed features of
      morphological distinctions of immunogenic structures small intestine fabrics in
      animals with various behavioral activity in the "Open field" test.

PMID- 21950011
TI  - [My profile and idea on education in anatomy].

PMID- 21950012
TI  - [Exploring and utilization of adult stem/progenitor cells toward regenerative
      medicine].

PMID- 21950013
TI  - [Comparative anatomical and comparative embryological studies on turtle body
      plan].

PMID- 21950014
TI  - [The functional role of stress proteins in ER-stress mediated cell death].

PMID- 21950015
TI  - [Legal measures in illicit drug detection: Results of questionnaires to the
      emergency departments in Japan].

PMID- 21950016
TI  - [Legal measures in illicit drug detection: A study on the doctor's duty in
      confidentiality and notice of patients information].

PMID- 21950017
TI  - [Legal measures in illicit drug detection: Management of urine tests in
      psychiatric treatment of methamphetamine dependence patients].

PMID- 21950018
TI  - [Legal measures in illicit drug detection viewed from the situation of the
      emergency doctors].

PMID- 21950019
TI  - [Brief story of the Clinical Toxicology Photo Contest].

PMID- 21950020
TI  - [Clinical Toxicology Photography Contest: Something coming to my mind].

PMID- 21950021
TI  - [Clinical Toxicology Photography Contest: Photograph and photo contest during my
      life].

PMID- 21950022
TI  - [Clinical Toxicology Photography Contest: I have a passion for taking photos of
      poisonous creatures].

PMID- 21950023
TI  - [Characteristics of plain computed tomography in an overdose: a high density
      deposition in the bottom of stomach].

PMID- 21950024
TI  - [Investigation of the Hounsfield number of drugs in stomach using computed
      tomography in vitro].
AB  - BACKGROUND: A high density area (HDA) that may represent ingested drugs was
      detected in the stomach of a patient with a drug overdose (OD) by computed
      tomography (CT). However, there is no prior evidence that drugs can be visualized
      as an HDA by abdominal CT. We investigated whether drugs can be imaged as an HDA
      by CT. METHODS: Ten tablets, 5 tablets, 1 tablet and 0.1 tablet of either Solanax
      (0.4 mg) or Depas (0.5 mg) or Tryptanol (10 mg) or Paxil (10 mg) or Wintermin (25
      mg) or Phenobal (30 mg) or Hiberna (25 mg) were each added to 10 ml of artificial
      gastric juice. We then measured the Hounsfield numbers immediately after mixing,
      1 hour later and 7 hours later using CT images. RESULTS: All of the drugs
      precipitated in the artificial gastric juice and these precipitations were imaged
      as HDAs over 100 Hounsfield units. Moreover, the drugs maintained high Hounsfield
      numbers after 7 hours although there was a trend to decrease sequentially.
      CONCLUSION: We demonstrated that the precipitated drugs in the artificial gastric
      juice could be imaged as HDAs by CT.

PMID- 21950025
TI  - [Detection of chloropyridinyl neonicotinoid insecticide metabolite 6
      chloronicotinic acid in the urine: six cases with subacute nicotinic symptoms].
AB  - Neonicotinoid is a recently developed insecticide with worldwide use that has
      been increasing. It acts as a nicotinic acetylcholine receptor agonist.
      Chloropyridinyl neonicotinoid is a subgroup of neonicotinoid, and are
      commercially available as imidacloprid, nitenpyram, acetamiprid, and thiacloprid.
      The maximum residue limits of acetamiprid for fruits and tea leaves are high in
      Japan, e.g. 5 ppm for grapes and 30 ppm for tea leaves. 6-chloronicotinic acid (6
      CNA) is a common metabolite in animals after exposure to chloropyridinyl
      neonicotinoids, but has not yet been detected in human urine. 'Spot' urine
      samples on the first visit and after were collected from eleven patients 6-52
      years-old, who visited X-clinic from August to December in 2008, within 24 hours
      after symptom onset with unknown origin. Urinary 6 CNA was detected in six out of
      the eleven patients (IC positive group), by ion chromatography and identified in
      twenty specimens of these six patients by liquid chromatography-mass spectrometry
      (LC/MS), maximum 84.8 microg/L from the first visit to the 20th visit. The
      sensitivity of ion chromatography for LC/MS was 45%, and the specificity was
      100%. The IC positive group showed headache, general fatigue, finger tremor, and
      short time memory disturbance in 100%, fever (> 37.0 degrees C), cough,
      palpitation, chest pain, stomachache, myalgia/muscle spasm/muscle weakness in
      83%, heart rate abnormality (sinus tachycardia, sinus bradycardia, or
      intermittent WPW syndrome) in 83%, high domestic fruits intake (> 500 g/day) in
      83%, high tea beverage intake (> 500 mL/day) in 66%. Five patients who were not
      among the IC positive group showed < 80%, < 40%, 60%, 60%, 20%, respectively. The
      patients gradually recovered through supportive therapy and the restriction of
      fruits and tea intake within several days to two months. In conclusion, urinary 6
      chloronicotinic acid, a common metabolite of chloropyridinyl neonicotinoid
      insecticide, was detected for the first time, from six patients with subacute
      nicotinic symptoms.

PMID- 21950026
TI  - [Lethal myocardial injury associated with hydrogen sulfide poisoning: report of
      two cases].
AB  - We investigated two cases of hydrogen sulfide poisoning in which the patients
      showed lethal myocardial injury. Both patients had planned to commit suicide by
      inhaling hydrogen sulfide. In case 1, a 17-year-old man was confused and was
      brought to our hospital by ambulance. An electrocardiogram (ECG) revealed diffuse
      elevation of the ST segment on the second hospital day. The patient recovered and
      was discharged from the hospital on the 15th day. However, he died suddenly on
      the 18th day. In case 2, a 21-year-old man was found lying on the floor and was
      admitted to our hospital. ECG showed tall T waves after 5 hr. Tachycardia and
      tachypnea occurred after 12 hr. After 16 hr, the ECG showed a marked elevation of
      the ST segment, and the patient developed cardiac arrest. Even though
      percutaneous cardiopulmonary support was used, he died on the 4th day. It is
      highly probable that myocardial injury asscociated with hydrogen sulfide
      poisoning was not caused by systemic hypoxia but by selective myocardial
      toxicity. These cases demonstrate that delayed presentation of a lethal
      myocardial injury should be considered while treating cases of hydrogen sulfide
      poisoning.

PMID- 21950027
TI  - [Case of olmesartan and amlodipine intoxication].
AB  - Although angiotensin II receptor blocker (ARB) is one of the most common drugs
      for hypertension in Japan, there are few reports of ARB intoxication. We report a
      case of persistent hypotension caused by intoxication of olmesartan and
      amlodipine. A 55-year-old female was transferred to our emergency center 4 hours
      after taking 180 mg of olmesartan and 140 mg of amlodipine. Continuous
      hypotension occurred after admission. We used norepinephrine up to 0.33
      microg/kg/min to keep her systolic blood pressure > 80 mmHg. We also used calcium
      gluconate as a treatment for amlodipine intoxication. Although it is predicted
      the abnormality of electrolyte balance, acid-base balance and renal dysfunction,
      she had recovered with no remarkable disability. With stabilization of her
      circulation, we reduced the dose of norepinephrine and stopped it on day 3, and
      she is discharged on day 5. Her serum olmesartan level was 3,980 ng/mL (normal
      C(max): 273.5 ng/mL), and serum amlodipine level was 104.9 ng/mL (normal C(max):
      2.51 ng/mL). We suggest that it is important to stabilize vital sign to treat ARB
      intoxication as same as other drug intoxication.

PMID- 21950028
TI  - [Case report of a dwarf lancehead snake bite in Gifu].

PMID- 21950029
TI  - [Psychotropic drugs].

PMID- 21950030
TI  - [Cancer pain and evaluation of the pain: preface and comments].
AB  - Cancer pain is very unpleasant often difficult to treat. Therefore, we should
      recognize the mechanisms of cancer pain and know the physical pain, psychological
      pain, social pain and spiritual pain as total pain. Besides, we must understand
      how to evaluate the cancer pain using the methods of assessment of cancer pain,
      and scales of pain degree (VAS, NRS, VRS, FRS, FVAS). New devices of pain
      measurement and the character of pain(McGill and Yatabe) are also introduced. The
      mechanism and grade of cancer pain often confuse us to recognize cancer pain. The
      articles in this special issue are useful for the evaluation and treatment of
      cancer pain. I feel happy if these articles contribute to the treatment of
      patients with cancer pain.

PMID- 21950031
TI  - [Mechanisms underlying generation of cancer pain].
AB  - As advances in cancer detection and treatment have increased the life expectancy
      of cancer patients, more attention to improving patient's quality of life (QOL)
      is needed. Among symptoms accompanying cancer, pain has strong impact on QOL.
      Most of cancer patients will experience moderate to severe pain and/or neuropathy
      during the course of their disease. Cancer pain can arise from different
      processes, either by direct tumor infiltration/involvement, or toxicity relating
      to chemotherapy used to treat cancer. The World Health Organization (WHO) has
      proposed a structured approach to drug selection for cancer pain, known as the
      "WHO analgesic ladder". However, several types of pain including bone cancer pain
      and chemotherapy-induced painful peripheral neuropathy are difficult to treat.
      The development of optimal analgesics for cancer pain has been hampered by the
      lack of understanding basic mechanisms that contribute to cancer pain. Recently,
      preclinical models of bone cancer pain and paclitaxel-induced painful peripheral
      neuropathy have been developed. These models have begun to provide insight into
      the mechanisms by which cancer pain is induced and how cancer pain-related
      sensory information is processed. In this paper, we review mechanism of cancer
      pain.

PMID- 21950032
TI  - [Physical pain in advanced cancer].
AB  - This chapter describes physical pain including pain, anorexia-cachexia syndrome,
      nausea-vomiting, abdominal distention, ascites, constipation and dyspnea. In
      effect, patients are more likely to present with several concurrent symptoms.
      Each of these symptoms is described separately in this chapter.

PMID- 21950033
TI  - [Mental distress in cancer patients].
AB  - Cancer patients receive treatments while being subjected to various distresses
      such as matters regarding their job, household, and purpose in life, as well as
      therapeutic problems. Each of these is a marked stress factor, which sometimes
      leads to the onset of mental disorders. About half of cancer patients undergo a
      psychiatric diagnosis during treatment. Anxiety and/or depression for which
      therapeutic intervention is needed is observed in 20 to 40% of them. Mental
      disorders need to be managed promptly because they cause not only distress owing
      to mental manifestations, but also reduce patients' motivation for treatment,
      impair their decision-making, and increase the incidence of suicide.

PMID- 21950034
TI  - [Social pain].
AB  - This chapter focuses on what social pain is and how it should be managed. In
      order to understand social pain in a cancer patient, it is necessary to recognize
      the change in the patient's daily life after the diagnosis of cancer. Because the
      degree of suffering and the relationships with family members and the people he
      or she worked with differ from patient to patient, it is important to note that
      the context of social pain is different in each patient. Five points shown below
      are essential in managing social pain. 1. Economical suffering may be alleviated
      by utilization of the social security system while taking into account each
      patient's standard of living. 2. Burdens on family members should be lessened,
      such as by not having them stay at the patient's bedside every day and letting
      them go home occasionally. 3. The normal patterns of communication, support, and
      conflict in the family should be identified, and the extent to which they have
      been disrupted by the illness should be assessed. 4. It is important to
      understand the ethnic, cultural, and religious background of the patient and the
      potential impact of their influence on the individual and the illness. 5.
      Practical or emotional unfinished business that the patient has needs to be
      identified, and efforts should be made to support fulfillment.

PMID- 21950035
TI  - [Spiritual pain].
AB  - We defined a spiritual pain as feelings of failure and regret at end-of-life,
      followed by hopelessness and worthlessness in patient's own life. In Japanese,
      spiritual pain should be assessed in patient's dignity, psycho-social factor, and
      prognostic stage, not only in religious context. And patient's spirituality
      should be supported with providing pain and symptom relief based on human
      relationships. "Sterbebegleitung" is a German proverb, introduced by Alfons
      Deeken, and seemed to be a suggestive word for such hope-recovering
      relationships.

PMID- 21950036
TI  - [Cancer pain assessment].
AB  - Adequate assessment is a necessary precondition for effective pain management.
      The objectives of cancer pain assessment include: (1) the accurate
      characterization of the pain, including the pain syndrome and inferred
      pathophysiology; and (2) the evaluation of the impact of the pain and the role it
      plays in the overall suffering of the patient. Because patient's self-report is
      the primary source of information for the measurement of pain, assessment is
      predicated on the establishment of a trusting relationship with the patient in
      which the clinician emphasizes the relief of pain and suffering, and encourages
      open communication about symptoms. Physical examination, including neurological
      evaluation, is necessary to identify the underlying aetiology of the pain
      problem, and clarify the extent of the underlying disease. Assessment is an
      ongoing and dynamic process that includes evaluation of presenting problems,
      elucidation of pain syndromes and pathophysiology, and formulation of a
      comprehensive plan for continuing care.

PMID- 21950037
TI  - [Pain intensity scales and assessment of cancer pain].
AB  - The ability to assess pain intensity is essential for both clinical trials and
      effective cancer pain management, although cancer pain assessment is complicated
      by a number of other bodily and mental symptoms such as fatigue and depression,
      all affecting quality of life. Several pain assessment tools have been shown to
      be reliable and reasonably valid in assessing cancer pain. Pain intensity scales
      are classified as self-report or observational and unidimensional or
      multidimensional. They include the numeric rating scales (e. g., 0 to 10), visual
      analogue scales (e. g., a 10-cm line with anchors such as "no pain" on the left
      and "severe pain" on the right; the patient indicates the place on the line that
      best represents the intensity of pain) or a verbal descriptor scales (e. g., "no
      pain", "mild pain", "moderate pain", "severe pain"). A variety of scales use
      drawings of faces (from smiling to distressed) for children or patients with
      cognitive impairment or dementia. The healthcare providers should use tools valid
      for the patient's age and cognitive abilities, with additional attention to the
      language needs of the patient.

PMID- 21950038
TI  - [PainVision].
AB  - Visual analogue pain scale (VAS) is believed to be a gold standard to evaluate
      pain intensity. However in practice it is not so easy to evaluate pain intensity
      by conventional assessment tool including VAS. Especially VAS is considered to be
      affected by a patient's mental state. Recently a newly developed device
      PainVision PS-2100 (Nipro Co., Osaka, Japan) for the quantitative analysis of
      perception and pain sensation was used to obtain pain intensity as "degree of
      pain". A new device PainVision calculating a "degree of pain" in addition to VAS
      may be a helpful tool to assess pain in cancer pain.

PMID- 21950039
TI  - [Evaluation of the quality of cancer pain-McGill Pain Questionnaire, Yatabe
      Guilford test].
AB  - In evaluating cancer pain, a comprehensive viewpoint for the so-called total
      pain, i. e., physical, mental, social as well as spiritual pains is required. The
      McGill pain questionnaire, which is often used to evaluate cancer pain, helps
      physicians understand the characteristics of the pain by asking each patient to
      express his/ her pain using verbal indicators. The Yatabe-Guilford test is also
      useful in evaluating the pain and QOL of the cancer patient, as it is a test
      designed to grasp the patient's personality.

PMID- 21950040
TI  - [Effect of single-shot interscalene block with less than 10 ml of local
      anesthetics on postoperative pain relief after arthroscopic rotator cuff
      reconstruction].
AB  - BACKGROUND: The effect of interscalene block on postoperative pain after
      arthroscopic rotator cuff reconstruction (ARCR) was evaluated. METHODS: Eighty
      four patients scheduled to undergo ARCR from April 2008 to March 2010 were
      assigned to a group receiving interscalene block with general anesthesia (Block
      group, n = 49) and a group receiving general anesthesia solely (General group, n
      = 35). In the Block group, ultrasound-guided single-shot interscalene block was
      performed before induction of general anesthesia with 0.375% ropivacaine 7-10ml.
      Postoperative pain intensity was recorded for 96 hours after the operation.
      Statistical analysis was performed with Mann-Whitney's U-test, and P < 0.05 was
      considered to be significant. RESULTS: Numerous rating scale (NRS) in the Block
      group was significantly lower than that in the General group immediately after
      the operation (median value: Block group = 0, General group = 6). Duration from
      the end of operation to the first administration of additional analgesics in the
      Block group (7 hours) was significantly longer than that in the General group (1
      hour). NRS in the Block group tended to be higher than that in the General group
      from the night of the day of operation. CONCLUSIONS: Single-shot interscalene
      block with less than 10 ml of ropivacaine before ARCR reduced postoperative pain
      only for several hours after the operation.

PMID- 21950041
TI  - [Usefulness of Epidrum for teaching identification of the epidural space].
AB  - BACKGROUND: Epidrum (ED) is a device to facilitate the epidural anesthesia
      procedure. Using ED, we can visually confirm the needle's penetration into the
      epidural space by collapse of the diaphragm. We investigated the usefulness of ED
      for teaching identification of the epidural space. METHODS: Forty parturients
      scheduled for cesarean section were randomly allocated to an ED group or loss of
      resistance (LOR) group. Epidural anesthesia was performed by residents
      (operators) under the instruction of advising doctors (observers). In the LOR
      group, the epidural space was identified by the conventional LOR technique using
      a glass syringe filled with normal saline. In the ED group, ED was attached to a
      Tuohy needle and was charged with 1.5 ml of air to expand its diaphragm. Ease of
      identification of the epidural space was scored by the operator and the observer.
      The time to identify the epidural space (TI) was recorded. RESULTS: TI in the ED
      group was significantly shorter than that in the LOR group. ED was superior to
      LOR for identification of the epidural space not only by operators but also by
      observers. CONCLUSIONS: The results suggest that ED is a useful device for
      teaching identification of the epidural space.

PMID- 21950042
TI  - [Administration of sugammadex to a patient with myasthenia gravis with fade of
      the train-of-four ratio].
AB  - A 50-year-old man (weight 87 kg, height 171 cm) with myasthenia gravis (MG) was
      scheduled for extended thymectomy under general anesthesia. His preanesthetic
      train-of-four ratio (T4/T1) was 59%. The first twitch of the train-of-four (T1)
      was 130% after calibration. We administered rocuronium 10 mg (0.11 mg x kg(-1))
      for tracheal intubation. Maximal suppression was achieved in 50 seconds. During
      the operation, we did continuous infusion of rocuronium to maintain T1 at 10%. We
      discontinued rocuronium infusion before the end of surgery. In patients with MG,
      deep levels of neuromuscular block can be achieved with less rocuronium. We
      hypothesized that the requirement of sugammadex in a patient with MG is less than
      that in normal patients. Therefore, we administered 0.5 mg x kg(-1) of
      sugammadex. After 5 min, T4/T1 had reached 54%, but T1 had not reached the
      control value; therefore, we administered additional 1.5 m x kg(-1) of
      sugammadex. Subsequently, T1 reached 120%. Patients with MG with fade on T4/T1
      require a full dose of sugammadex, identical to the dose administered to normal
      patients.

PMID- 21950043
TI  - [Anesthetic management of cardiac pheochromocytoma resection and coronary artery
      bypass grafting under cardiopulmonary bypass].
AB  - We experienced pheochromocytoma resection and coronary artery bypass grafting
      under cardiopulmonary bypass (CPB). The patient was a 69-year-old man who was
      first diagnosed with atherosclerotic angina. During operation, his blood pressure
      increased at induction and manipulation of the tumor under CPB, associated with
      an increased serum noradrenaline concentration. Starting operation, we monitored
      using transesophageal echocardiography (TEE), and used that view for diagnosis
      and anesthetic or hemodynamic management. It was especially useful after tumor
      resection. Surgical and hemodynamic management was facilitated by TEE. TEE was
      useful to make a diagnosis of cardiac pheochromocytoma, to determine the area of
      resection, to determine the surgical repair, and to make a decision of
      hemodynamic management in this complicated patient. We suggest that perfoming
      these cases under CPB and TEE is recommended for stabilization of hemodynamic
      states.

PMID- 21950044
TI  - [Torsade de pointes (TdP) observed during general anesthesia for cerebral
      aneurysm clipping in a patient with QT prolongation].
AB  - A 55-year-old woman underwent emergency cerebral aneurysm clipping for
      subarachnoid hemorrhage (SAH). Her past and family history was unremarkable.
      Preoperative blood examinations were within normal ranges except for a slight
      decrease in serum potassium level. ECG showed a prolonged QTc interval (0.54
      sec). General anesthesia was induced with propofol, fentanyl and vecuronium, and
      maintained with 1-1.5% sevoflurane, 50% nitrous oxide in oxygen and intermitted
      doses of fentanyl. About three hours after starting the operation, bigeminal
      pulse appeared followed by torsade de pointes. This arrhythmia returned to sinus
      rhythm by continuous infusion of lidocaine, and operation was performed
      completely. At the end of the operation, prolonged QT interval (QTc 0.71 sec) was
      noted. Her postoperative course was unremarkable and she was discharged on
      postoperative day 44. QT prolongation is a frequently seen ECG abnormality in a
      patient with SAH. In anesthetic management in this situation, it is important to
      monitor QT interval closely as well as to use anesthetics that would not
      exacerbate QT interval prolongation.

PMID- 21950045
TI  - [Transient paraplegia due to epidural hematoma after catheter withdrawal].
AB  - A 58-year-old man with hypertension underwent laparoscopic distal gastrectomy
      under general and epidural anesthesia. Preoperative laboratory date revealed a
      normal platelet count and normal coagulation profile. Epidural puncture was
      successfully performed at the T9-10 intervertebral space on the first attempt
      without bleeding. An epidural catheter was smoothly inserted 5 cm cephalad. On
      the third postoperative day, paraplegia due to thoracic epidural hematoma
      developed shortly after extraction of the catheter. At that time, his blood
      pressure was 190/102 mmHg because of a pain due to walk. On using a hypotensive
      drug, his blood pressure fell. Ten minutes later, paraplegia disappeared
      spontaneously. It is suggested that the spinal cord of the patient was subjected
      to transient pressure hematoma. A decline in blood pressure may have caused the
      blood to spread through the epidural space, such that the neurologic symptoms
      disappeared.

PMID- 21950046
TI  - [Torsade de pointes associated with severe bradycardia after induction of general
      anesthesia].
AB  - An 80-year-old woman with chronic atrial flutter/fibrillation, and chronic renal
      failure underwent ileocecal resection. The preoperative electrocadiogram showed
      normal QT interval. Temporary pacemaker catheter was inserted for sinus arrest (5
      6 sec) the day before operation. Anesthesia was induced with remifentanil 0.5
      micro x kg(-1) min(-1), thiamylal 125 mg, and rocuronium 30 mg after intravenous
      atropine sulfate 0.5 mg. Because the heart rate was increased with atropine
      sulfate, the pacemaker was not started. Anesthesia was then maintained with
      intravenous remifentanil and sevoflurane-air-oxygen. Just after induction of
      anesthesia, sinus bradycardia occurred, and 9 minutes after tracheal intubation,
      ECG suddenly showed torsade de pointes (TdP) and the arterial blood pressure
      decreased leading to asystole. We immediately started cardiopulmonary
      resuscitation, and TdP stopped spontaneously within 1 minute. We started
      pacemaker (VVI, 60 beats x min(-1)) and intravenous injection of lidocaine, and
      TdP did not recur. In this case, TdP seemed to have occurred because of
      bradycardia-induced abnormal QT prolongation. This should be considered the risk
      of lethal arrhythmia in patients with severe bradycardia including TdP.

PMID- 21950047
TI  - [Interscalene block combined with general anesthesia under spontaneous breathing
      in a patient with a giant bulla].
AB  - Respiratory management for patients with a giant bulla during anesthesia should
      avoid positive-pressure ventilation to reduce the risk of barotraumas. We report
      a case of anesthetic management of a 42-year-old man with a giant bulla who had
      an elective surgery for biopsy of a tumor on his left elbow. Balanced anesthesia
      consisting of general anesthesia was given under spontaneous breathing combined
      with interscalene brachial plexus blockade for intra- and postoperative analgesia
      for the elbow surgery. The patient was monitored by electrocardiography, non
      invasive arterial pressure, SpO2, endtidal CO2 tension and bispectral index.
      Ultrasound-guided interscalene block was performed with the patient awake. After
      injection of 0.75% ropivacaine 20 ml and 1% lidocaine 16 ml for brachial plexus
      block, general anesthesia was induced with a bolus of fentanyl 100 microg to
      reduce cough reflex and propofol using target control infusion with a 2 microg x
      ml(-1) plasma concentration. The airway was maintained with a size 4 LMA-Proseal,
      which was inserted with care under spontaneous breathing. There were no serious
      complications such as pneumothorax in perioperative period. We performed
      successful anesthetic management, without any complications, combined with
      interscalene brachial plexus block and spontaneous breathing in a patient with a
      giant bulla.

PMID- 21950048
TI  - [Choice of induction with, or standby of, extracorporeal lung assist (ECLA) in
      anesthetic management of bronchoscopic yttrium-aluminium-garnet (YAG) laser
      treatment of airway tumor].
AB  - Bronchoscopy with an yttrium-aluminium-garnet (YAG) laser is often used to resect
      benign and malignant airway tumors and for relief of associated airway stenosis.
      Complications of this procedure include airway obstruction and hemorrhage.
      Partial extracorporeal circulation for YAG laser resection in the airway may be
      helpful in minimizing these complications. Extracorporeal lung assist (ECLA)
      should be available for such bronchoscopic surgery, although it is not always
      required. We managed the general anesthesia for bronchoscopic YAG laser resection
      of airway tumors in two patients. The first case was a 60-year-old man with a
      right bronchial tumor that had invaded into the trachea across the carina. The
      narrowest inner diameter of the part of the trachea affected by the lesion was 3
      mm. ECLA was initiated for a bronchoscopic YAG laser resection. The second case
      was a 74-year-old woman with a metastastic lung tumor from osteosarcoma. The
      narrowest inner diameter of the lesion in the right truncus intermedius was 4 mm.
      ECLA was kept on standby for possible complications in the bronchoscopic YAG
      laser resection. These treatments were completed successfully in both patients
      without any adverse events. ECLA is a useful supporting technique for performing
      bronchoscopic YAG laser treatment safely ECLA is recommended where a bronchial
      lesion invades the trachea and crosses the carina, and where a tracheal lesion
      will not allow passage of a tracheal tube under the bronchoscope. However, ECLA
      may be kept on standby for a airway tumor limited to one main bronchus, and for a
      peripheral bronchial lesion, and even for an invasive tracheal lesion through
      which the tracheal tube under the bronchoscope can pass. Whether it is used or
      kept on standby depends on the location and severity of airway compromise caused
      by the airway lesions.

PMID- 21950049
TI  - [Palliative care in an acute care setting at Kumamoto Regional Medical Center].
AB  - BACKGROUND: The Japanese government promotes allowing patients in palliative care
      to choose where they wish to end their lives. Emergency hospital admissions are
      inevitable for those cared at home. There are not enough cancer centers in Japan
      with palliative care facilities and hospices to admit these patients without
      prior consultation. METHODS: We examined outcomes and characteristics of patients
      receiving palliative care who were transported by ambulance to our hospital.
      RESULTS: From April 2007 to March 2010, 58 patients under palliative care came to
      our emergency department by ambulance. Eight of the 58 (14%) were admitted
      between midnight and 8 am and 21 (36%) on Saturdays or Sundays. We were consulted
      for 19 patients (32%) within one week and saw 14 of these on the day they were
      admitted. Chief complaints were disturbed consciousness (31%), dyspnea (28%),
      pain (14%) and general fatigue (7%). Fifty patients (86%) came directly from
      their homes and the others from another hospital. Thirteen patients (22%) died
      within 48 hours, and 8 (14%) were discharged after their symptoms were treated.
      Thirty-three (57%) patients died and 4 (7%) were discharged within ten days.
      CONCLUSIONS: We admitted patients under palliative care into the acute care
      setting to Kumamoto Regional Medical Center any time.

PMID- 21950050
TI  - [On the diversity of the primary steps of embryonic development in the caudate
      amphibians].
AB  - Literary data on the peculiarities of the egg cleavage process in various
      representatives of the order of caudate amphibians consisting of 10 families have
      been considered. It has been recognized that in considerable number of species of
      Plethodontidae, Cryptobranchidae, and some other families, the synchrony of
      divisions is lost already after the 8-celled stage of the cleavage in large, yolk
      rich and unpigmented eggs. A"standard" cleavage of early embryos of caudate
      amphibians, which had been described in the text-books on developmental biology
      and consists approximately of 10 synchronous divisions of comparatively small
      eggs, is characteristic only of the families Ambystomatidae and Salamandridae
      including 19.3% of species within the order Caudata. However, within each of
      these families there seems to be a number of species with a "nonstandard" type of
      early cleavage. The evolutionary relationships between two main types of early
      embryogenesis within the order Caudata are discussed.

PMID- 21950051
TI  - [Comparative characteristics of new human embryonic stem cell lines SC5, SC6,
      SC7, and SC3a].
AB  - Numerous human embryonic stem cell lines with different genetic background are
      widely used as cell models for fundamental, biomedical and pharmacological
      research. New hES cell lines SC5, SC6, SC7, and SC3a are derived from the
      blastocysts and maintained on mitotically inactivated human feeder cells. All
      derived hES cell lines passed through more than 120 cell population doublings,
      retained normal diploid karyotype and ability of in vitro differentiation in the
      derivates of three germ layers. These lines express the markers of
      undifferentiated hES cells: Oct-4, Nanog, SSEA-4, TRA-1-60, and alkaline
      phosphatase. Moreover, undifferentiated cells of SC5, SC6, and SC7 lines
      expressed germ line specific genes DPPA3/STELLA and DAZL and did not express
      somatic lineages specific genes. In contrast, undifferentiated cells of SC3a line
      did not express DPPA3/STELLA and DAZL but expressed extra embryonic endoderm cell
      markers GATA4 and AFP. Double staining of SC5 and SC3a colonies by antibodies
      against transcription factors Oct-4 and GATA4 has demonstrated that most SC3a
      cells in colonies were positive for both factors. Furthermore, the cells of SC5,
      SC6, SC7 lines but not of SC3a line formed teratomas containing the derivates of
      the three germ layers. These results indicate that, in contrast to the other cell
      lines, the cells in the SC3a colonies represent an early committed cell
      population. Moreover, expression of the multidrug resistance transporter gene
      ABCG2 was detected in undifferentiated cells and differentiating embryonic bodies
      during 10 days of all lines by immunofluorescent and RT-PCR analyses, whereas RT
      PCR analysis has revealed up-regulation of the ABCB1 transporter gene expression
      in differentiating embryoid bodies of SC5, SC6, and SC7 cells only. Thus, these
      findings demonstrate different characteristics and differentiation potential of
      SC5, SC6, SC7, and SC3a hES cell lines which were derived in different
      conditions.

PMID- 21950052
TI  - [Features of the expression of a meristem-specific WOX5 gene during nodule
      organogenesis in legumes].
AB  - In recent years, the role of WOX genes encoding homeodomain transcription factors
      in the development of the apical meristem of shoots and roots has been actively
      investigated. However, the role of WOX genes in the control of the cell
      proliferation in other meristem types is poorly studied. In our work, we have
      studied the role of the WOX5 gene in the development of the meristem in nitrogen
      fixing nodules developing on the roots of legumes in a symbiosis with rhizobia.
      We have shown that the WOX5 gene is involved in the development of the nodule
      meristem in legumes, have quantitatively evaluated the gene's expression at
      different nodule formation stages, and have studied the localization of its
      expression using a construction containing the WOX5 promoter conjugated with a
      reporter gene. The role of the WOX5 transcription factor in the nodule
      organogenesis and its possible interaction with the hormonal system in the course
      of the nodule development has been discussed.

PMID- 21950053
TI  - [The changes in contents and composition of phenolic acids during cell xylem
      growth in scots pine].
AB  - The contents and composition of alcohol soluble phenolic acids were studied
      during cell xylem growth in the course of wood annual increment formation in the
      stems of Scots pine. The cells of cambium zone, of two stages of expansion growth
      and the outset of secondary thickening zone (before lignification) were
      successively gathered from the stem segments of 25-old pine trees in the period
      of earlywood xylem formation with constant anatomical and histochemical control.
      The contents of free and bound forms of phenolic acids, isolated by 80% ethanol
      from tissues, as well as of their ethers and esters were calculated both per dry
      weight and per cell. The content and relation of the fractions and the
      composition of phenolic acid have been found to change significantly from cambium
      zone to the outset of tracheid secondary thickening. The character of the
      variations depends on a calculation method. According to the calculation per cell
      the amount of free and bound phenolic acids and in their composition of esters
      and especially ethers increased at the first step of expansion growth zone,
      decreased at the second one and rose again in the outset of secondary wall
      deposition. In dependence on the stage of cell development the pool of bound
      phenolic acids exceeded of free acid pool in 2-5 times. Sinapic and ferulic acids
      dominated in the composition of free hydroxycinnamic acids. The content and
      composition of hydroxycinnamic acids in ethers and esters depended on cell
      development phase. In cambium p-coumaric and sinapic acids were principal
      aglycons in ethers, at other stages these were sinapic and caffeic acids. The
      esters in cambium zone included essentially p-coumaric acid and at the other
      stages - sinapic and ferulic acids. At the first phase of growth benzoic acid was
      connected principally by ester bonds. The pool of these esters decreased from the
      first phase of growth to the outset of cell wall thickening and in proportion to
      this the level of free benzoic acid rose.

PMID- 21950054
TI  - [Morphogenetic lability of reproductive structures in Ruppia maritima
      (Ruppiaceae, Alismatales): from two lateral flowers to a terminal flower].
AB  - Flowers of Ruppia are normally arranged into an open two-flowered spike, but
      sometimes the two lateral flowers are congenitally united with each other and
      form a terminal flower-like structure. This developmental abnormality resembles
      those described in well-investigated mutants of model organisms of developmental
      genetics such as Arabidopsis Antirrhinum. A study of Ruppia allows investigating
      morphogenetic lability of this feature in natural populations. These data will be
      important for understanding evolutionary transitions between open and closed
      inflorescences. This paper presents first data on frequencies ofterminal flower
      like structures in natural populations of Ruppia maritima and first observations
      of their development. Vascular supply of inflorescences with free and united
      flowers is compared for the first time. Strong differences in frequencies of
      occurrence of terminal flower-like structures among examined natural populations
      are revealed. Data on variation of organ numbers in flowers of plants from
      different populations allow hypothesizing that increased size of floral primordia
      is a factor that plays a role in their amalgamation into ajoint primordium of a
      terminal structure. Vascular system of inflorescences of R. maritima with united
      flowers is quite similar to the vascular system of a flower and nothing
      contradicts a hypothesis on terminal position ofthis structure. Transversally
      inserted stamens in inflorescences with united flowers are usually of inverted
      polarity. This appears to be the first documented example of an inversion of
      relative polarity of stamens and carpels in angiosperms.

PMID- 21950055
TI  - [Development and metabolism of chicken embryos in the prenatal period under
      acoustic stimulation].
AB  - Acoustic influence on the metabolic process in the last days of incubation of
      embryos of domestic chicken was found. It was shown that the changes that appear
      under the influence of acoustic signals lead to a decrease in incubation time. As
      a result of acoustic hyperstimulation, gaseous exchange and growth of the embryo
      continue to follow a power dependence characteristic of an earlier period of
      embryogenesis, i.e., the depression typical of these processes in the end of
      incubation is arrested. In acoustically stimulated embryos, a tendency toward a
      decrease in the total energy expenses on growth and metabolism is observed in the
      period from 17 days of incubation up to hatching, but the daily expenses on
      energetic exchange and growth are higher under acoustic influence than in the
      control group.

PMID- 21950056
TI  - [Different action of the APETALA1 gene on the development of reproductive organs
      in flowers of the abruptus mutant of Arabidopsis thaliana (L.) Heynh].
AB  - The APETALA1 (AP1) gene of A. thaliana codes type II MADS protein with domains
      MADS, I, K, and C. The role of K- and C-domains in the functioning of AP1 protein
      is poorly investigated. The analysis of phenotypic manifestation of mutations
      disrupting the activity of various domains of the protein product allows us to
      obtain information on the function of domains and, thereby, on the structural
      functional organization of the gene. We investigated the action of mutant alleles
      of the AP1 gene whose protein products are probably lacking the functionally
      active domains K (ap1-20), K- and C-domains (ap1-1 and ap1-6), and C-domain (ap 1
      3) on the flower morphology in abr mutant (the ABRUPTUS/PINOID gene allele). It
      was detected that, unlike the ap 1-20 allele, the presence of ap 1-3, ap1-6, and
      ap 1-1 alleles results in reduction of a number of the generative organs in the
      flowers of the double mutants abr ap1-3, abr ap1-6, and abr ap1-1. It was
      suggested that C-domain of the AP1 protein prevents the alteration of
      determination of the type of reproductive organs at ectopic expression of the AP1
      gene in the inner whorls of a flower in the abr mutant.

PMID- 21950057
TI  - [Self-synchronization of the protein synthesis rhythm in HaCaT cultures of human
      keratinocytes].
AB  - In cultures of human keratinocytes HaCaT contained in a serum-free medium on
      glass, a circahoralian rhythm of protein synthesis was found similar to the one
      in hepatocytes in vitro. The intensity of the synthesis was determined by the
      inclusion of 3H-leucine corrected for the pool of free marked leucine. Rhythm was
      studied in washed 1- or 2-day cultures after the change of the medium. The medium
      conditioned with keratinocytes HaCaT synchronized the rarefied hepatocyte
      cultures nonsynchronous in the control. Therefore, the keratinocytes liberate
      synchronizing factors into the medium. A BAPTA-AM chelator of calcium ions
      eliminates the protein synthesis rhythm both in dense hepatocyte cultures
      synchronous in the control and in the HaCaT keratinocyte cultures. The effect of
      the H7 inhibitor of protein kinases was analogous. Thus, both in keratinocytes
      and hepatocytes, self-synchronization of fluctuations of the intensity of protein
      synthesis takes place. The mechanism of self-synchronization is the calcium
      depending phosphorylation of cell proteins.

PMID- 21950058
TI  - [Antioxidants as aromatic amino acid oxidation products].
AB  - The accumulation of UV photolysis products of amino acids tyrosine and
      tryptophan, which possess an antioxidant activity, has been studied by the method
      of luminol-activated chemiluminescence. The amount of antioxidant products was
      judged by the value of the total antioxidant potential of a UV-irradiated
      solution, the measure of which was the distance between the peaks of the
      chemiluminescence curve in the system 2,2'-azo-bis(2-amidinopropane)hydrochloride
      + luminol in a UV-irradiated and an unirradiated samples (induction period,
      tau(i)). Simultaneously, the absorption and fluorescence spectra of unirradiared
      and UV-irradiated amino acid solutions were recorded. It was shown that, upon the
      exposure of a tryptophan solution to radiation, the accumulation of the
      fluorescent product N-formyl kynurenine (lambda(em) = 325 nm, lambda(max) = 440
      nm) occures, and the curve of its accumulation was similar to the curve of growth
      of tau(i) photoproducts produced during UV-radiation. When a tyrosine solution
      was irradiated, the main fluorescent product was dityrosine (lambda(em) = 310 nm,
      lambda(max) = 415 nm). Nevertheless, the dose dependencies of the formation of
      dityrosine, and the total antioxidant potential (tau(i)) were completely
      different. It was found that another product of tyrosine UV-photolysis,
      dioxyphenylalanine, possessed a pronounced antioxidant activity. It was concluded
      that the main antioxidants produced under UV-irradiation of tryptophan is formyl
      kynurenine, and under the irradiation of tyrosine, dioxyphenylalanine.

PMID- 21950059
TI  - [Influence of inorganic phosphate on the production of free radicals in UV
      irradiated frozen tyrosine solutions].
AB  - The role of inorganic phosphate as a catalyzer of the production of tyrosyl
      radical in frozen tyrosine solutions irradiated with near UV light at 77K has
      been demonstrated by the EPR method. It was shown that the increase in the yield
      of tyrosyl radicals at pH < 7 correlates with the production of H* atoms and can
      be explained by the fact that phosphate acts as an acceptor of photoejected
      electrons. At pH > 7, the increase in the yield of tyrosyl radicals is
      accompanied by the production of phosphate radicals and OH* and is caused,
      presumably, by the catalysis of the formation of triplet states of tyrosine
      molecules by the HPO4(2-) form of phosphate, the fact shown by a number of
      authors. A quantitative estimation of relative concentrations of photosensitized
      paramagnetic products was carried out on the basis of computer analysis of
      resultant EPR signals.

PMID- 21950060
TI  - [On the optimal folding of protein molecules].
AB  - The process of globular structure formation from a long molecular chain has been
      examined. In the course of this process, various regions of the chain interact
      with one another. We classify the bonds formed during this process as "correct"
      and "erroneous" ones. The term "correct" bonds implies the bonds characteristic
      for a completely formed native globular structure. All other bonds can be treated
      as "erroneous". It was demonstrated that the process of globule formation may
      proceed actually without the formation and the following decay of "erroneous"
      bonds. Our model permits one to avoid the examination of numerous "erroneous"
      variants since, between the regions of the chain that form "correct" bonds, long
      distance interactions characterized simultaneously by high selectivity take
      place. The existence of interactions of this kind facilitates the drawing
      together and subsequent interaction of just these regions of the chain that yield
      "correct" bonds. Based on the data bank analysis, it was demonstrated that the
      model elaborated is valid not only for abstract structures but also for real
      polypeptide chains capable of forming protein globules and superhelical fibrils.

PMID- 21950061
TI  - [Stabilization energy of the compact Caf1(13-149) subunit from Yersinia pestis].
AB  - It has been shown by a variety of methods (circular dichroism, viscosimetry,
      intrinsic fluorescence, and fluorescence of labels) that, as in the case of small
      globular proteins the folding-unfolding transition in the Caf1(13-149) subunit
      under the action of two denaturants (urea and 1,3-dimethylurea) occurs between
      two major states (unfolded and compact). However, the free energy of the compact
      structure is only 8/9-9/2 kJ/mol (similar values for single-domain small proteins
      are in the range of 21-63 kJ/mol).

PMID- 21950062
TI  - [Lactate dehydrogenase from the tetraploid weatherfish Misgurnus fossilis during
      temperature adaptation: determination of structural differences in two forms of
      the enzyme by molecular modeling methods].
AB  - A structural analysis of two lactate dehydrogenase M4 protein forms has been
      performed. These structures are the protein products of two lactate dehydrogenase
      gene (LDH-A) copies in the weatherfish Misgurnus fossilis genome after thermal
      adaptation (acclimation) to 5 degrees C and 18 degrees C. The localization of
      three earlier identified amino acid substitutions (Gly214Val, Leu304Ile,
      Asp312Glu) has been determined, and the molecular dynamics simulation and
      computer modeling of two forms of the enzyme from skeletal muscles LDH-M4 have
      been carried out. After molecular dynamics trajectory calculations carried out at
      5, 18, and 25 degrees C, the intersubunit distances for all structures used in
      calculations have been determined. It has been found that the Gly214Val
      substitution localized in the intersubunit region leads to a new intersubunit
      interaction, which plays a role in the stabilization of tetrameric enzyme
      structure after the adaptation to 18 degrees C.

PMID- 21950063
TI  - [Investigation of permolecular structure of lipase from Rhizopus niveus].
AB  - It has been shown by classical biophysical and biochemical methods in combination
      with atomic microscopy that lipase from Rhizopus niveus exists in a water
      solution as a dimer with a molecular weight of 96 kDa. The rate of splitting of
      triglycerides by a dimeric molecules is twice that of monomers. The heat
      stability of the monomeric form of lipase at temperatures of 20-60 degrees C is
      significantly higher than that of the native molecule.

PMID- 21950065
TI  - [Computer simulation of the transcription process in the discrete model of DNA
      molecule].
AB  - A mathematical model of the nonlinear dynamics of DNA has been considered, which
      takes into account the real sequence of the nitrous base. Soliton solutions
      describing the nonlinear mechanisms of the regulation of DNA transcription have
      been obtained. It has been shown that the soliton-like excitation may both fade
      in the terminator of the first gene and pass into the promotor of the second
      gene. Thus, transcription processes in one gene and two consecutive genes are
      modeled.

PMID- 21950064
TI  - [Interaction of protein with charged colloidal particles].
AB  - The functional state of three proteins of different molecular weight (urease,
      lactate dehydrogenase, and hemoglobin) in the presence of the linear
      polyelectrolytes poly(allylamine hydrochloride) (PAA) and sodium
      poly(styrenesulfonate) (PSS) in the dissolved state and of the same
      polyelectrolytes bound to the surface of microspheres has been investigated.
      Microspheres were prepared by consecutive absorption of oppositely charged
      polyelectrolytes so that the outer layer of the shell was PAA for the acidic
      protein urease, and PSS for the alkaline proteins LDH and hemoglobin. It was
      shown that the dissolved polyelectrolyte completely inactivates all three
      proteins within one minute with a slight difference in the time constant. (By Hb
      inactivation are conventionally meant changes in the heme environment observed
      from the spectrum in the Soret band.) In the presence of microspheres, the
      proteins were adsorbed on their surface; in this case, more than 95% of the
      activity was retained within two hours. The proportion of the protein adsorbed on
      microspheres accounted for about 98% for urease, 72% for Hb, and 35% for LDH, as
      determined from the tryptophan fluorescence data. The interaction of hemoglobin
      with another type of charged colloidal particles, phospholipid vesicles, leads to
      the destruction of the tertiary structure of the protein, which made itself
      evident in the optical absorption spectra in the Soret band, as well as the
      spectra of tryptophan fluorescence and circular dichroism. In this case,
      according to circular dichroism, the percentage of alpha-helical structure of Hb
      was maintained. The differences in the physical and chemical mechanisms of
      interaction of proteins with these two types of charged colloidal particles that
      leads to differences in the degree of denaturing effects are discussed.

PMID- 21950066
TI  - [Contribution of enthalpy to the energetics of complex formation of aromatic
      ligands with DNA].
AB  - The energy contributions of electrostatic, van der Waals interactions, hydrogen
      bonds, and interactions of charge transfer type to the enthalpy of complex
      formation of the double-stand DNA with the antitumor antibiotics daunomycin,
      nogalamycin, and novantron, as well as the mutagens ethidium bromide and
      proflavine have been calculated. According to the calculations, the van der Waals
      component (except for nogalamycin) is energetically favorable during complex
      formation of the antibiotics with DNA, and the contributions of H bonds and
      electrostatic interactions are unfavorable, with the probability of charge
      transfer in the complexes being low. It has been shown that the relatively low
      value of the experimental enthalpy of binding is the sum of components greater in
      absolute value and different in the sign, which is the cause of large errors in
      estimating the total enthalpy of complex formation of aromatic ligands with DNA.

PMID- 21950067
TI  - [Verification of a decrease in the rigidity of the phage lambda DNA polymeric
      chain in low ionic strength aqueous solutions by testing the polymer-polymer
      interlink interactions].
AB  - Changes in the rigidity of the polymetric chain of phage lambda double-strand DNA
      have been studied by laser correlation spectroscopy. It was shown that, as the
      ionic strength increases, the effect of the screening of the hydrodynamic
      interaction of the links of the polymeric chain specific for polymeric coils
      arises in a DNA solution. It is assumed that the screening occurs when the
      threshold of the overlapping of DNA coils is achieved. The overlapping of coils
      is the result of a previously observed significant rise of DNA coil size from
      abnormally small DNA coils in low ionic strength buffers (about 10(-2) M Na+ or
      less) to maximum possible large coils in the 5SSC and 5SSC-like buffers. Further
      analysis of the far interlink interactions in linear lambda phage DNA coils in
      similar buffers at pH 7 and 4 confirms the earlier proposal about the role of H+
      ions in the appearance of abnormally small DNA coils. The abnormal decrease in
      the DNA coil size in low ionic strength buffers is not a specific feature of
      lambda phage DNA only.

PMID- 21950068
TI  - [Assessment of the distribution of nucleic acid intercalators in yeast cells by
      the pseudospectral image analysis].
AB  - The intracellular location of nucleic acid intercalators (NAI) in live (not
      fixed) Saccharomyces cerevisiae cells has been studied using fluorescence
      microscopy combined with computer pseudospectral image analysis. Three NAI: the
      anthracycline anticancer drug doxorubicin and the nucleic acid dyes ethidium
      bromide (E) and 4',6-diamidino-2-phenylindole (DAPI) were used. All three NAI
      were shown to be localized in nuclei and mitochondria. In contrast to DAPI, which
      interacted only with DNA, a large fraction of doxorubicin and ethidium bromide
      apparently bound to mitochondrial membranes. Upon combined application, a
      competition between these intercalators for binding sites in the nuclear and
      mitochondrial DNA occurred. It was concluded that this approach may be used in
      designing new DNA-targeted drugs and in preliminary studies of their interaction
      with eukaryotic cells.

PMID- 21950069
TI  - [Effect of physicochemical properties of murine liver lipids on the interrelation
      between the parameters of their composition].
AB  - The effect of properties of liver lipids on the interrelation between the
      contents of different lipid fractions has been studied on nine groups of intact
      SHK female mice. To reveal interrelations, lipids were divided into four groups
      depending on their antioxidative activity, prooxidant properties, antiperoxide
      activity, and the content of peroxide in lipids. The data obtained indicate that
      the physicochemical properties of lipids affect the biosynthesis and degradation
      of phospholipids, which plays a significant role in the origination of
      consequences under the action of unfavourable factors on biological objects
      having the different intensity of oxidative processes.

PMID- 21950070
TI  - [A method for the detection and characterization of GABA(A) receptors by calcium
      sensitive fluorescent probes].
AB  - A method for the detection and characterization of GABA(A) receptors of neurons
      has been developed, which is based on the measurement of the activity of
      potential-dependent calcium channels using the fluorescence of the two-wavelength
      calcium-sensitive probe Fura-2. The method makes it possible to detect the
      ligands of GABA(A) receptors and determine the constants of activation and
      inhibition as well as the type of inhibition. The object of investigation was a
      young (two- to four-day-old) rat hippocampal cell culture in which GABA induces
      the depolarization and a transient increase in Ca2+ concentration in the cytosol
      of neurons due to the activation of potential-dependent calcium channels. It was
      shown that a short-time application of GABA induces a decrease in the amplitude
      of calcium responses to subsequent addition of the depolarizing agents GABA or
      KCl. However, at low amplitudes of calcium responses to the addition of GABA,
      this reducing effect on the subsequent addition of KCl was insignificant. It was
      found that the amplitudes of calcium responses to KCl and GABA are linearly
      dependent on the angular coefficient b = 3.41. This enabled one to develop a
      method of normalizing calcium signals, which makes it possible to compare
      experiments performed on different days and different cultures. By using this
      normalization technique, the values of EC50 = 2.21 +/- 0.14 ?M and the Hill
      coefficient = 1.9 +/- 0.2 were estimated. The blocker of potential-dependent
      calcium channels nifedipine suppressed simultaneously the amplitudes of calcium
      responses to the addition of KCl and GABA. In this case, the linear relationship
      between the amplitudes of calcium responses to the addition of KCl and GABA was
      retained. To verify the validity of the method, the constant of inhibition of a
      calcium signal and the type of inhibition for known noncompetitive and
      competitive antagonists of GABA(A) receptors were determined.

PMID- 21950071
TI  - [Transport of protons and potassium ions across the membranes of bacteria
      Enterococcus hirae depends on ATP and nicotineamide adenine dinucleotides].
AB  - The transport of protons and potassium ions across the membranes of the bacteria
      Enterococcus hirae growing in an alkaline medium (pH 8.0) or under experimental
      conditions (pH 7.5) during glucose fermentation accomplished by a KtrI-system of
      absorption of potassium ions, which can interact with F0F1-ATPase to form at H(+)
      K(+)-pump, has been studied. It was found on cells with a high membrane
      permeability that the administration of nicotinamideadenine dinucleotides results
      in the potassium absorption, which is insensitive to the inhibitor of F0F1-ATPase
      N,N'-dicyclohexylcarbodiimide. It is assumed that, along with the KtrI system,
      which interacts with F0F1-ATPase, a separate or another K+ absorption system
      operates in these bacteria under particular conditions, which is dependent on
      NAD(+)+NADH. Presumably, these interact with this system, changing its
      conformational state required for the transition to the "active" form.

PMID- 21950072
TI  - [Changes in the chromatin structure of lymphoid cells under the influence of low
      intensity extremely high-frequency electromagnetic radiation against the
      background of inflammatory process].
AB  - Using the alkaline single cell gel electrophoresis technique (comet assay),
      changes in chromatin structure of peripheral blood leukocytes and peritoneal
      neutrophils have been studied in mice exposed to low-intensity extremely high
      frequency electromagnetic radiation (42.2 GHz, 0.1 mW/cm2, 20 min at 1 h after
      induction of inflammation) against the background of the systemic inflammatory
      process. It was revealed that the exposure of mice with the developing
      inflammation leads to a pronounced decrease in the level of DNA damage to
      peripheral blood leukocytes and peritoneal neutrophils. It is supposed that the
      changes in the chromatin structure of lymphoid cells have a genoprotective
      character in the inflammatory process and can underlie the mechanisms of
      realization of antiinflammatory effects of the electromagnetic radiation.

PMID- 21950073
TI  - [On the nature of the light-induced component of dark respiration of plants].
AB  - The data on the isotope composition of carbon of CO2 of the light-induced dark
      respiration component have been analyzed using the oscillation model of
      photosynthesis. It was concluded that this component originates during the
      transformation of sucrose accumulated by the plant in the oxygenase phase of
      photosynthetic oscillations in the light period into organic acids. The
      transformation occurs in the dark period. It this process, C-3 and C-4 atoms,
      which determine the "heavy" isotope composition of carbon of CO2 of the light
      induced dark respiration component are split off from the hexose link of sucrose.

PMID- 21950074
TI  - [Role of endogenous porphyrins in the effects of low-intensity laser radiation of
      the red region on free radical processes in the blood of rats under experimental
      endotoxic shock].
AB  - The role of endogenous porphyrins in the effects of laser radiation of the red
      region (632.8 nm) on free radical processes in the blood of rats under endotoxic
      shock induced by the administration of lipopolysaccharide B (25 mg/kg) has been
      studied. The measurements of the functional activity of polymorphonuclear
      leukocytes (the method of luminol-dependent chemiluminescence), the superoxide
      dismutase activity of blood plasma (using nitro blue tetrazolium), and the degree
      of lipid oxidation of erythrocyte membranes (the method of fluorescence of cis
      parinaric acid) have been carried out. It has been found that low-intensity laser
      radiation strongly affects all processes examined irrespective of the
      administration of lipopolysaccharide B. The effect of radiation was most
      pronounced in animals injected with the polysaccharide, the changes being
      dependent on the concentration of endogenous porphyrins in samples.

PMID- 21950075
TI  - [Stability of lepidopterous pheromone molecules of forest insects to
      environmental factors].
AB  - The interactions of the pheromones of some representatives of the Lepidoptera
      order with each other and with materials contained in the forest air, as well as
      the effect of electromagnetic radiation on pheromone have been studied. It was
      found that the reactions of pheromones with substances contained in the forest
      air are irreversible and proceed with the liberation of heat. Electromagnetic
      radiation affects very strongly the structure of pheromones. In this case, a
      pheromone molecule is activated and can readily enter into reaction.

PMID- 21950076
TI  - [Relationship between the critical phases of the physiological state of insect
      during supercooling and its dielectric permeability].
AB  - The relationship between critical temperatures causing the cold torpor and
      freezing of liquid fractions of the body of honeybees and their dielectric
      permeability has been studied. It has been shown that the temperature at which
      the freezing of liquid fractions occurs, as distinct from the temperature
      inducing the cold torpor, depends on age and seasonal generation of insects. It
      has been found that changes in the temperature causing the torpor and freezing
      correlate with jumps of dielectric permeability.

PMID- 21950077
TI  - [Some regularities of the pulse rate variability].
AB  - Histograms of heat rate for 878 persons of both sexes aged from 3 to 83 years
      have been analyzed. The total data sampling was more than one hundred thousand
      pulse beats. Summary bar charts (variance pulsograms) were built up separately
      for men and women. Within the range of 60-75 beat/min, the peaks with the beat
      rates corresponding to 60, 61, 63, 65, 68, and 75 beat/min were observed, their
      values being twice as big as those of the neighbouring ones. Within the range of
      79-99 beat/min, minima were observed with beat rates of 79, 87, 91, 94, 97, and
      99 beat/min. The distribution of these beat rates can be approximately described
      by the members of Fibonacci series from the determining beat rate of about 59-60
      beat/min (maximuma) and about 101/102 beat/min towards a decrease in the beat
      rate (minima). The determining beat rates of about 60, 101, and 162 beat/min may
      be evidence of the hierarchy, which is also approximately described by the array
      close to the Fibonacci series. Within the range of 101 to 115 beat/min, the peaks
      for men are marked that correspond to the harmonic series with a period of 2
      beat/min, i.e., 101, 103, 115 beat/min.

PMID- 21950078
TI  - [Dielectric parameters of ascitic and pleural fluids in the microwave range in
      different nosologies].
AB  - The dielectric parameters of ascitic and pleural fluids formed in the human body
      in oncological and nononcological diseases of different nosology have been
      estimated in the range between 400 MHz and 1.2 GHZ. The dependence of refractive
      and absorption indices of ascitic and pleural liquids on the signal frequency and
      mass concentration of dissolved substances was found. Common regularities and
      distinctions in the behavior of their dielectric properties were revealed.

PMID- 21950079
TI  - [Investigation of metabolic paramagnetic centers in the blood of patients with
      prostate adenocarcinoma prior to and after the plastic orchectomy].
AB  - Paramagnetic centers in the blood of patients with prostate adenocarcinoma have
      been studied prior to and after plastic orchectomy by EPR. It has been shown that
      significant alterations in blood paramagnetic centers occur after the surgery.
      These alterations point to an improvement of antioxidant properties of the blood.
      Specifically, the content of the Fe(3+)-transferrin complexes increased, and the
      number of inactivated adrenoreceptors, MetHb, and Mn(2+)-containing complexes
      decreased. It was found that, along with improvement of the antioxidant
      properties of the blood, a significant decrease in the intensity of lipid
      peroxidation in the blood of the patients occurs.

PMID- 21950080
TI  - [The most important stages of the mechanism of action in vivo of carcinogen
      diethylnitrosoamine and its effect on the synthesis of RNA, proteins, DNA, and
      deoxyribonucleotides].
AB  - The mechanisms of nitric oxide (NO) generation from exogenous and endogenous
      sources, induced by the addition of the carcinogen diethylnitrosoamine (DENA) to
      rat organism have been studied. Within 15 h after the addition of DENA, the
      carcinogen itselt acts as an exogenous NO donor. The products of protein
      degradation (the process induced by DENA) act as endogenous donors of NO. It was
      shown that the generation of nitric oxide from diethylnitrosoamine leads to deep
      hemic and tissue hypoxia and induces the inactivation of oxygen-dependent
      enzymes, including ribonucleotide reductase, and the inhibition of ATP synthesis.
      Under these conditions, the protein synthesis and as a consequence the synthesis
      of deoxyribonucleotides and DNA are strongly suppressed; i.e.,
      diethylnitrosoamine produces the effect similar to the action of the antibiotic
      cycloheximide, an inhibitor of translation. The administration of cycloheximide
      to the animal organism also led to the appearance of a considerable amount of
      nitric oxide in the blood. It is assumed that nitric oxide initiates (on the
      administration of the carcinogen) or at least enhances (on the administration of
      cycloheximide) the blockage of the synthesis of the protein,
      deoxyribonucleotides, and DNA. In response to the disturbance of protein
      synthesis, the complex of enzymes is activated that accomplish the utilization of
      the degradation products of proteins, including the inducible form of NO
      synthase.

PMID- 21950081
TI  - [A change in the state of silica in water under external weak influences].
AB  - The role of silica impurities, which can significantly contribute to the state of
      water environment and its response to external factors, has been studied. The
      nonequilibrium state of silica in water, its evolution with time, and its
      dependence on the prehistory of a water sample were shown. Reversible freezing
      thawing of water induces long-term changes in the ratio of the monomeric and
      polymeric forms of silica, which slowly relax to the initial state. It was shown
      that the "field-free" magnetic vector potential has a real effect on freezing.
      With the use of the alternating vector potential, its maximum effect was
      registered at frequencies of 3.5-4 Hz. It was proposed that this results from the
      stochastic resonance during the polymerization of silicic acid.

PMID- 21950082
TI  - [Cognitive control in recognition of emotionally negative face in 5-10-year-old
      children].
AB  - We used the experimental model of cognitive visual set, designed by D.N. Uznadze,
      to study the influence of previous experience on emotional face expression
      recognition in pre-school (6.1 +/- 0.3 years) and elementary school (10.5 +/- 0.1
      years) children. Our results suggest that the ability to form a cognitive set to
      an angry face expression develops in ontogenesis in strong concordance with
      functional maturation of prefrontal cortex that takes place at the age of
      approximately 10 years. At this age children display almost the same level of set
      plasticity and a similar kind of erroneous perceptions during set actualization
      as grown-ups. Children of younger age (6.1 +/- 0.3 years) display more
      perceverative erroneous perceptions, or assimilative illusions (probably of a
      priming origin), than the above mentioned groups. We consider this to be a result
      of a more strong influence of previous experience in their case.

PMID- 21950083
TI  - [Sex differences of spatial-temporal organization of biopotentials of the brain
      in adults and child 5-6 years old].
AB  - Research of topical features of spatial structure of EEG distant relationships
      has been performed with correlation and coherent analyses of EEG for 26 children
      of 5-6 years old (12 boys and 14 girls) in comparison to the data at 33 adult
      subjects (15 men and 18 women). Men have much higher level of EEG
      intrahemispherical relations of posttemporal and frontal regions of the left
      hemisphere whereas women have the higher level prevalence of interhemispheric
      interactions, especially of bilateral-symmetrical arials of both hemispheres.
      Preschoolers have another character of sex differences in the system organization
      of inter-regional interactions of brain biopotentials than adults. In
      particularly the girls have exceeding of EEG distant relations in the same zones
      of left hemispheres, where at men such relations have exceeding in comparison
      with woman. The obtained data shows that the pronounced sexual dimorphism of
      inter-regional interactions of cortical biopotentials at adults and at children
      is formed, first of all, owing to of EEG distant relations topology differing in
      males and females subject. Investigation sex differences of spatial-temporal
      organization of biopotentials of the brain in children can promote forming of
      more hole and deep understanding of role of sex factor in development of human
      brain system activity.

PMID- 21950084
TI  - [Baseline gamma activity EEG and induced responses to facial stimuli of the
      visual cognitive set].
AB  - Power spectra of cortical potentials of baseline activity during interstimuli
      intervals (4 s; Fourier transform in the frequency band of 1-60 Hz) and short
      term (0.8 s) induced responses to facial stimuli (wavelet transform in the 15-60
      Hz band) were assessed in the study of the visual cognitive set to facial
      expression. Significant differences between groups of subjects with different set
      rigidity were observed only at the set-testing stage. Estimation of the short
      term (0.8 s) induced responses of the wavelet spectra in the group with plastic
      set revealed an increase in the power (in comparison with the power of background
      activity) of the gamma2 band (41-60 Hz) in the left hemisphere of the temporal,
      central and occipital areas, whereas in the group with rigid set these power
      spectra decreased. At the same time the power in the gamma1 band (21-40 Hz) was
      significantly lower (at the same level with the rigid form), indicating a
      discrete nature and functional selectivity in the gamma frequency band.

PMID- 21950085
TI  - [The relationship between O2 saturation mixed venous blood and pressure in the
      trunk of the pulmonary artery for healthy people and patients with heart
      defects].
AB  - Investigated the relationship between pulmonary artery pressure (P(LA)) and the
      oxygen saturation of mixed venous blood (S(V)) in 12 group's of surveyed
      individuals (1750 men and 1026 women). We have identified a function (P(LA))
      between P(LA) = f(S(V)), and a function (S(V)) S(V) = f(P(LA)) was estimated for
      each group based on direct measurements of P(LA) and S(V). We found, that factors
      were subordinated to the dependences for a P(LA) = f(S(V)), P(LA) = a x (S(V))(
      b), where b = = -0.2284a + 0.6564 men - and b = -0.285a + 1.2947 in women and the
      other for -S(V) = f(P(LA)), S(V) = c x (P(LA))(-d) where d = -0.251311n(c) +
      1.0212; (R2 = 0.8993) men and d = -1.96451n(c) + 2.852; (R2 = 0.9674) women. Each
      group occupies a position on the curves represented by equations. The subjects
      with a diagnosis of functional murmur in the heart and patients with congenital
      stenos is of the aortic valve form a group, provisionally designated as "group
      norms", which is characterized by its dependence P(LA) = f(S(V)), and -S(V) =
      f(P(LA)). The men in "group norms" additionally include patients with coronary
      heart disease. The equation - CO = Cons.O2/(KEK(S(A) - (c x (P(LA))(-d). It
      relates the P(LA), caused by different reasons, with the corresponding saturation
      of mixed venous blood, and when the saturation of mixed venous blood is also
      caused by various factors, set the corresponding P(LA). Interdependent changes in
      physiological parameters of blood circulation and gas exchange in humans is
      established equilibrium between systemic and pulmonary circulation.

PMID- 21950086
TI  - [Clusters structure of psychomotor and coordination sphere of primary school
      children].
AB  - The main objective of our research is characterization of various motor profiles
      among primary school age children. We examined 89 Moscow schoolchildren of 8-10
      years old, not involved in sports. We analyzed 25 indices from psychomotor,
      psychophysiologic, posturography and locomotor testing during our research.
      Children were divided in 4 groups according to its motor coordination character
      similarity by applying cluster analysis (k-means method). Thereby we obtained 4
      clusters which, as we suppose, can be identified as different types of motor
      coordination or "individual motor profiles" of 8-10 years old children. The
      results of our research shows that there are no significant differences in age,
      gender, body composition within clusters, thus it can be used during sport
      selection process. The most typical features of 1st cluster representatives are:
      the ability to anticipate and a high wrist speed; the 2nd cluster representatives
      are more successful in rapid, rhythmic, automatic actions, based on a mechanism
      of intrinsic programming. Representatives of the 3rd cluster are notable for a
      low level of postural control, smooth, accurate and rhythmic arm actions based on
      a visual feedback, and advanced sense of tempo and space sense. Representatives
      of the 4th cluster shows highest level of development of coordination ability,
      which are significant for them in reaching results in various hard-coordination
      sports and labor activities.

PMID- 21950087
TI  - [Mutual influences of upper and lower extrimities during cyclic movements].
AB  - The possibility of muscle activation of passive arm during its cyclic movements,
      imposed by active movements of contralateral arm or by experimenter was studied,
      as well as the influence of lower extremities cyclic movements onto arm muscles
      activity. In addition to that the activity of legs muscles was estimated in
      dependence on motor task condition for arms. Ten healthy supine subjects carried
      out opposite movements of arms with and without stepping-like movements of both
      legs. The experiment included three conditions for arm movements: 1) the active
      movements of both arms; 2) the active movements of one arm, when other entirely
      passive arm participated in the movement by force; 3) passive arm movement caused
      by experimenter. In the condition 2) additional load on active arm was applied
      (30 N and 60 N). In all three conditions the experiment was carried out with arms
      movements only or together with legs movements. The capability of passive moving
      arm muscles activation depended on increasing afferent inflow from muscles of
      contralateral arm was demonstrated. Emerging electrical activity was modulated in
      the arms movements cycle and depended on the degree of active arm loading. During
      combined active movements of arms and legs the reduction of activity in the
      flexor muscles of shoulder and forearm was observed. Concomitant arms movements
      increased the magnitude ofelectromiographic bursts during passive stepping-like
      movements in the most of recorded muscles, and the same increasing was only
      observed in biceps femoris and tibialis anterior muscles during active legs
      movement. The increasing of loading of one arm caused essential augmentation of
      EMG-activity in the majority of recording legs muscles. The data obtained are the
      additional proof of existence of functionally significant neuronal interaction
      both between arms and between upper and lower extremities, which is evidently
      depend on the intraspinal neuronal connections.

PMID- 21950088
TI  - [Biochemical indicators of blood at sportsmen at joint application of muscular
      and food loading].
AB  - The results of a blood biochemical testing among highly skilled sportsmen,
      coaching under different power conditions accompanied by veloergometer dosed
      stress and a trial carbohydrate breakfast are considered in the research. The
      quantity of glucose, crude protein, albumines, calcium, magnesium, potassium,
      chlorine and sodium were difined in the blood serum. Essential differences in the
      indices of glucose, magnesium, sodium, chlorine among skilled and non-skilled
      sportsmen were taped. The results got testify about the presence of expressed
      alterations in a power and water-salt interacting at trainings under different
      power conditions.

PMID- 21950089
TI  - [The physiological analysis of the possible reasons of hypoxemia in
      weightlessness].
AB  - In spaceflight at cosmonauts decrease of oxygen partial pressure in capillary
      blood on 12-30% in comparison with preflight values is revealed. The analysis of
      the possible reasons and mechanisms of hypoxemia in weightlessness is carried
      out. On the basis of this analysis the conclusion becomes that the principal
      cause of oxygen partial pressure decrease in blood of cosmonauts at microgravity,
      with the big degree of probability, is venoarterial bypassing. It is connected
      with increasing of venous blood passage through lungs, without full gas exchange
      in capillaries of small circulation circle.

PMID- 21950091
TI  - [The center of pathological (toxic) action of metals in an people organisms and a
      role of galvanic currents in its induction].
AB  - Chronic influence of metals on an organism differs from their sharp toxic action.
      In some exposed to long chronic metals influence people appear chronic
      inflammatory diseases, including oncological, on a background of neurologic
      symptoms develop. Today the overwhelming majority of the population is more 40-50
      years old have metal alloys in the form of dental artificial limbs and various
      implantates in a body. Because of metal corrosion in organisms of these people
      concentration of metal ions is created. Galvanic currents induced at presence of
      any metals in an organism, promote corrosion, and carry of metal ions inside
      organism. If these currents are strong (the potential difference more 150 MB),
      local inflammatory pathologies development in organism due to concentration in
      the center of metal ions.

PMID- 21950090
TI  - [Profile of sex steroids in healthy volunteers' urine during experiment in
      isolated object].
AB  - The quantitative determination a number of endogenous steroids and their
      metabolites in urine of healthy volunteers by means of gas chromatography - mass
      spectrometry was performed. The dynamic of steroid profile of healthy individuals
      as well as possible ranges of several endogenous steroid parameters have been
      investigated. Samples were obtained during 105-days experiment with 6 volunteers
      in isolated on ground modules where were modeling the main life conditions which
      could influence the steroid profile: meal volume and composition, water
      consumption, motion activity, air composition and temperature, rate sleep -
      wakefulness and emotional tension. The parameters of urine steroid profile of
      healthy volunteer which were affected by life conditions in isolated object were
      revealed. The parameters of individual and group variability of steroid profile
      and its dependence from definite experiment conditions - change of salt
      consumption periods, autonomy of vital activity were detected.

PMID- 21950092
TI  - [Features of the circadian rhythm of temperature of the skin at children of 8-9
      years and young men and girls].
AB  - Problem of the present work was studying age features circadian rhythm of
      temperature of a skin with application of a method "Termochron iButton". Day
      night rhythm of a skin temperature at two age-grades was investigated: boys and
      girls of 8-9 years and young men and girls of 20-22 years. For this purpose
      monitoring temperature during 48 hours with an interval of registration 10
      minutes has been lead. Are revealed authentic chronobiological differences: mesor
      temperatures above at girls, than at boys, and at young men, above, than at
      girls. Amplitude of a circadian rhythm is above at boys and at girls. Researches
      chronobiological parameters in the different terms of day have shown, that an
      average level of temperature at night below at all examinees. The amplitude at
      adult people in the different terms of day does not differ, while at children it
      above in the night term.

PMID- 21950093
TI  - [Continuity and prospects of development of researches in area system
      integrativity of psychophysiology of functional state and cognitive activity].
AB  - In the review one of actual problems of psychophysiology in studying a phenomenon
      of integration of mechanisms of regulation of state of a brain and features of
      the organization is discussed by a brain of cognitive activity. Basic value of
      results of long-term researches of academician N.P. Bechterevoj and of her school
      is opened in the field of neurophysiology of functional states as bases of the
      organization of mental activity in conditions of direct, long and sparing contact
      to a cortical and subcortical structures of a brain, with the help long-term
      intracerebral electrodes. Arguments about a commensurability and complementary
      value similar on amplitud-time parameters slow and superslow gradual changes of
      neurophysiological processes registered simultaneously in identified zones of
      subcortical structures of a brain and with removal from a surface of a head in
      cortical projections of basic integrativity of the centres are submitted.
      Representations about a brain as difficultly organized "swimming" many-contour,
      neurodinamic informational-controlling suprasystem with hierarchically,
      probability a principle of the organization different on speeds and intensity of
      processes of the ability to live participating in maintenance of a condition of
      rest, mental conditions and cognitive activity are formulated and argued. At the
      limited set universal neurodinamic "languages", the brain has the multiregister
      mechanism of regulation of conditions and selectivity of mechanisms of the
      integration providing the contribution differing on information maintenance
      gradual neurophysiological of processes of different levels of the structurally
      functional organization in formation of brain systems of maintenance of concrete
      kinds of cognitive activity.

PMID- 21950095
TI  - [Psychophysiology of sports addiction (exercises addiction)].
AB  - Addiction is a prevalent and growing concern in all aspects of our modern
      society. There are considerable concerns for the growing frequency of addictions
      to drugs, alcohol, gambling, eating, and even sex. Though exercise is generally
      accepted as a positive behaviour that has many benefits associated with enhanced
      physical and psychological wellbeing, there is an increasing awareness that
      exercise addiction is becoming a common phenomenon. Theories regarding how
      exercise can become addictive, and studies of withdrawal from exercise are
      reviewed. Several physiological mechanisms, including endogenous opioids,
      catecholamines, functional asymmetry of brain activity and thermoregulation have
      been implicated in exercise dependence.

PMID- 21950094
TI  - [Central mechanisms of sleep-wakefulness cycle].
AB  - Brief anatomical, physiological and neurochemical basics of the regulation of
      wakefulness, slow wave (NREM) sleep and paradoxical (REM) sleep are regarded as
      representing by the end of the first decade of the second millennium.

PMID- 21950096
TI  - [Radiation adaptive response as a stress reaction of a cell].
AB  - The published data on the primary changes that occur in human peripheral blood
      lymphocytes after small dose irradiation in vitro (SDI), as well as relation
      between these changes and the adaptive response mechanism (increase of
      radioresistance of lymphocytes after SDI) have been analyzed. The author has come
      to a conclusion in favor of the absence among the revealed primary changes of any
      traces of a specific inducible mechanism that protects a cell from exterior
      influences and elevates cell radioresistance. The changes in cell radioresistance
      following the SDI comprise only an insignificant part of all the changed
      characteristics. There are large numbers of mechanisms by which radioresistance
      changes and they are poorly studied at that. The author speculates that the
      adaptive response isn't a specific radiobiological protective phenomenon, but it
      is rather a type of the cell stress reaction that is evoked by external
      influences. Signals that trigger transition to a state of stress, as well as the
      signals to implement adaptive functions, thus restoring the normal state, can be
      represented, for example, by increased concentrations of reactive oxygen species,
      and most likely by as yet unknown metabolic changes. An irradiated cell transfers
      into the state of stress and mobilizes all possible ways to increase resistance
      to any damaging effects, radiation including. What particular way of increasing
      radioresistance will be used depends on the genotype, experiment conditions, etc.
      The consequences of stress could cause more rapid cell division, malignant
      transformations and increased stability of malignization, hormesis and many other
      things.

PMID- 21950097
TI  - [The peculiarities of polymorphism of XPD and XRCC1 repair genes in cells of Down
      and Ehlers-Danlo syndrome patients characterized by increased radiosensitivity].
AB  - Codon 312 and 751 polymorphisms ofXPD gene and codon 399 polymorphism of XRCC1
      gene of peripheral blood lymphocytes in patients with Down syndrome (DS) (46
      individuals), Ehlers-Danlo syndrome (EDS) (47 individuals) and in a group of
      healthy donors (control) (40 individuals) have been studied. Frequency of XPD
      genotype (G312G) coding for the most effectively functioning form of XPD protein
      was lower in patients with DS (26%) than in a group of healthy donors (42.5%) (p
      = 0.035), whereas no significant differences with the control were revealed for
      this codon in patients with EDS. No patients with XPD genotype (C751C) (p =
      0.036) were revealed in a group of EDS patients, while this genotype was found in
      16% of a group of healthy donors and in 17% of patients with DS. The trend of
      XRCC1 genotype frequency reduction (A399A) (p = 0.085) in EDS patients (3.9%)
      compared with the group of healthy donors (13.5%) and DS patients (13.3%) has
      been obtained. These data show that polymorphisms of the excision repair genes
      under study are accompanied by an elevated individual radio sensitivity in
      patients with DS. Genes investigated (their polymorphic variants) did not
      participate in the mechanisms for radio sensitive phenotype formation in EDS
      patients.

PMID- 21950098
TI  - [Rapid dicentric assay of human blood lymphocytes after exposure to low doses of
      ionizing radiation].
AB  - The probability of losses of different chromosome aberrations during the
      dicentric chromosome assay of metaphase cells with incomplete sets of chromosome
      centromeres was estimated using a mathematical model for low doses of ionizing
      radiation. A dicentric assay of human blood lymphocytes without determination of
      the total amount of chromosome centromeres in cells without chromosome
      aberrations (rapid dicentric assay) has been proposed. The rapid dicentric
      analysis allows to register chromosome aberrations in full compliance with the
      conventional classification. The experimental data have shown no statistically
      significant difference between the frequencies of dicentric chromosomes detected
      by rapid and classical dicentric chromosome assays of human lymphocytes exposed
      to 0.5 Gy of 60Co gamma-rays. The rate of the rapid dicentric assay was almost
      twice as high as that of the classical dicentric assay.

PMID- 21950099
TI  - [Alteration of UV-sensitivity of mice peritoneal macrophage plasma membranes by
      calcium ions].
AB  - Effect of Ca2+ ions on UV-induced mice peritoneal macrophage plasma membrane
      damage has been studied. Drop of the extracellular Ca2+ concentration has been
      found to result in a reduced expression of this damage. On the contrary, a raised
      intra- and extra-cellular Ca2+ level is associated with a higher number of cells
      with damaged plasma membranes. These findings make it possible to suggest that
      this change in the plasma membrane photosensitivity might be a result of
      alterations in the membrane lipid matrix electrical stability owing to UV-induced
      lipid photo-peroxidation. This study has also shown that free radical
      peroxidation of membrane lipids plays a significant part in UV-induced cell
      damage.

PMID- 21950100
TI  - [Ways of realizing apoptosis of human lymphocytes induced by UV-light and
      reactive oxygen species].
AB  - Changes of DNA structural condition, the level of membrane Fas-receptor
      expression, caspase-3 functional activity, concentrations of Ca2+, p53 and
      cytochrome c proteins of human lymphocytes in dynamics of apoptosis development
      induced by UV-light (240-390 nm) at doses 151, 1510, 3020 J/m2 and reactive
      oxygen species (superoxide anion-radical, hydroxyl radicals, hydrogen peroxide,
      singlet oxygen) have been studied. UV-light and reactive oxygen species have been
      established to induce fragmentation of lymphocyte DNA after 20 h incubation of
      the modified cells. It has been shown, that the increase in the expression level
      of membrane death Fas-receptors is observed during 1-5 h after exposure
      oflymphocytes to UV-light and ROS compared with intact cells. Also revealed is
      augmentation of lymphocyte caspase-3 functional activity 4 h after generation of
      singlet oxygen, hydroxyl radical and hydrogen peroxide addition, as well as 8 and
      24 and 6 and 8 h after UV-irradiation of the cells at doses 151 and 1510 J/m2,
      correspondingly. Using DNA-comet method made it possible to tape that DNA damages
      (single-strand breaks) appear 15-20 min after lymphocyte UV-irradiation at doses
      1510 and 3020 J/m and addition of hydrogen peroxide in concentration 10(-6) mol/l
      (C1 type comet) and reach their maximum 6 h after modification of the cells (C2
      and C3 type comets). It has been observed, that 6 h after exposure oflymphocytes
      to hydrogen peroxide and UV-light at doses 1510 and 3020 J/m2, the p53 level of
      investigated cells raises. It has also been shown that the higher level of
      calcium in lymphocyte cytosol in conditions of UV-light exposure (1510 J/m2) and
      exogenous generation of reactive oxygen species is caused by Ca2+ exit from
      intracellular depots as a result of activating the components of the
      phosphoinositide mechanism for transferring information into a cell. Ideas about
      correlation between alterations of the calcium level and initiation of programmed
      cellular destruction of human lymphocytes after exposure to UV-irradiation and
      ROS is proposed. The authors come to the conclusion about the leading role of
      receptor-mediated (Fas-dependent) caspase- and p53-dependent ways of realizing
      apoptosis oflymphocytes induced by UV-light at doses 151 and 1510 J/m2 and active
      oxygen metabolites. The pattern of the possible intracellular events leading to
      apoptotic destruction of lymphocytes after their UV-irradiation is offered.

PMID- 21950101
TI  - [Effect of natural and postradiation volatile secretions of mice on the immune
      reactivity and blood cellularity of irradiated animals].
AB  - It has been shown that natural and postradiation volatile urinary secretions of
      mice can remotely restore the immune reactivity and blood indices reduced as a
      result of exposure of laboratory mice to ionizing radiation. Antibody formation
      in spleen of gamma-irradiated (1 Gy) CBA strain mice was increased after exposure
      of both syngeneic and allogeneic animals with urine volatile secretions. Volatile
      natural secretions of intact mice have a more pronounced antibody stimulating
      activity than volatile secretions from animals exposed to gamma-radiation.
      Immunoreactivity ofy-irradiated C57B16 strain mice with low olfactory reactivity
      increases only after their exposure with volatile secretions of intact syngeneic
      animals. The total number of leukocytes and lymphocytes in the peripheral blood
      of gamma-irradiated (1 Gy) inbred mice increases after exposure with secretions
      obtained from them before irradiation. The role of hemo-signalling in the
      selective stimulation of immunity and blood content in conditions of radiation
      damage is discussed.

PMID- 21950102
TI  - [Particularities of blood lymphocyte response to irradiation in vitro in breast
      cancer patients].
AB  - DNA breaks and their repair efficiency were analyzed in irradiated in vitro
      lymphocytes (at doses 1 Gy, gamma-radiation of 60Co, dose rate 1 Gy/min) isolated
      from peripheral blood of 41 untreated patients with breast cancer and 25 healthy
      donors using the DNA comet assay under non-denaturing conditions (mainly double
      strand DNA breaks (DSB), as well as apoptotic cell death using the DNA halo
      assay. To estimate the expression of bystander effect, the cells were incubated
      in a culture medium obtained from lymphocytes irradiated in vitro at doses 1 Gy.
      The average DSB level in blood lymphocytes of breast cancer patients was shown to
      be significantly higher (p < 0.05) compared with that in control donors. In
      general, the following effects were observed in irradiated in vitro lymphocytes
      of cancer patients: (1) increased sensitivity to y-radiation-induced DNA DSBs
      compared with lymphocytes from healthy donors, (2) reduced repair efficiency of
      these damages. Incubation of irradiated blood lymphocytes in a medium from
      irradiated cells led to an increased relative number of DNA DSBs and an elevated
      fraction of cells dying through apoptotic pathway both in blood lymphocytes from
      cancer patients and control donors. However, these non-targeted effects were more
      expressed for the blood lymphocytes of breast cancer patients.

PMID- 21950103
TI  - [Possibilities of using MIGI-K protective activity under conditions of
      radionuclide contamination].
AB  - Experimental studies of the mussel hydrolyzate (MIGI-K) have shown that this
      preparation can enhance both general and radiation resistance of the organism.
      Moreover, MIGI-K promotes elimination of incorporated radionuclides from the
      organism. Some properties of this preparation, in particular, the absence of
      toxicity or harmful side effects, have made it possible to apply MIGI-K as an
      adaptogen, that is, a food supplement oftherapeutic and preventive action used to
      increase radionuclide excretion in the Chernobyl emergency clean-up workers.

PMID- 21950104
TI  - [Effect of indometofen on the survival and bone marrow hemopoiesis of mice
      exposed to acute external gamma- or X-ray irradiation].
AB  - The purpose of the study is evaluation of radioprotective effectiveness of
      indometofen at its prophylactic administration in conditions of acute
      irradiation. Evaluation of radioprotective efficiency was performed by studying
      the 30-day survival rate, life expectancy, structure of deathly irradiated mice,
      and bone marrow hemopoiesis using methods of endogenous and exogenous colony
      formation. The prophylactic application of indometofen at doses 30 mg/kg for 5
      days before irradiation has been observed to protect mice against radiation death
      induced by gamma or X-ray exposures at doses LD(50-70/30), increasing their
      survival rate by 16-44%, and reduce severity of post radiation disorders of bone
      marrow hemopoiesis.

PMID- 21950105
TI  - [Changes in response of neurons in visual area of cerebral cortex of rabbits to
      flashes of light under the influence of low-intensity physical factors of non
      ionizing nature].
AB  - The effect of various physical factors (SM F: 460 O; microwave EMF: 6 GHz,
      continuous mode, 200 microW/sm2; sound: clicks of 50 Hz, 6 db above a threshold
      of EEG response) on responses of neurons in visual area of cerebral cortex of
      rabbits to light flashes (1 Hz, 1 ms, 0.62 J) has been studied in experiments on
      27 rabbits. The character of changes depended on the indicators for a background
      and for the response to the isolated action of light. Inhibition, rather than
      activation, was observed at a significantly higher initial frequency. Effect of
      the factors of magnetic nature was similar to the action of sound (inadequate
      irritant for the visual area). Inhibitory reactions were observed more frequently
      (significant result for the group of neurons), with their amplification at a
      combined action of irritants (SMF and microwave EMF; SMF and sound). The basic
      character of changes was limited to the drop in the pulsation frequency at the
      first phase of activation and to the increase in the latent periods of the first
      and second active phases. Other indicators for reaction to light flashes actually
      didn't change.

PMID- 21950106
TI  - [Radioecological investigation of the soil cover of eastern Urals State
      radioactive reserve and neighboring areas].
AB  - The contamination levels and spatial distribution of 90Sr and 137Cs in the soil
      cover of the Eastern Ural State Radioactive Reserve and neighboring areas have
      been studied. Situated in the Chelyabinsk region, the Reserve embraces the
      frontal part of the Eastern Urals Radioactive Trace. This Trace emerged in 1957
      as a result of the nuclear accident at the Production Association "Mayak". In the
      studied areas, the content of radionuclides in soils decreases exponentially as
      the distance from the source of contamination increases. 90Sr received by the
      soil cover as a result of the accident in 1957 has remained the main contaminant
      of the Reserve central part (97% of the total contamination). Its contribution
      throughout western neighboring areas reduces up to 67%, which decreases the
      effect of 90Sr on the environment. Within eastern neighboring areas, soil is
      mainly contaminated by 137Cs received as a result of the wind disseminated dried
      sediments from the shores of Lake Karachay (1967) that was used for dumping high
      level radioactive waste. Also observed was enrichment of forest litters with this
      radionuclide due to current atmospheric fallout.

PMID- 21950107
TI  - [Russian National Committee on Non-Ionizing Radiation Protection. Decision.
      "Electromagnetic field of mobile phones: the impact on the health of children and
      young people"].

PMID- 21950108
TI  - [The 57th session of science UNO about the influence of nuclear radiation].

PMID- 21950109
TI  - [Russian scientific conference with international participation "actual problems
      of toxicology and radiobiology"].

PMID- 21950110
TI  - [Plant growth promoting microorganisms as alternative to chemical protection from
      pathogens (review)].
AB  - The review analyses data on physiological and biochemical influence of
      rhizospheric and endophytic microorganisms promoting plant growth (PGPR-plant
      growth promoting rhizobacteria) on induced resistance of plants and the
      possibility of its use in plant cultivation to protect crops from pathogens and
      phytophages. Resistance of plants provided by PGPR due to their endosymbiotic
      interrelationships is directly achieved because they produce peptide antibiotics
      and hydrolases ofchitin and glucan and also because plants form their own system
      of induced resistance, followed by changes in the balance of defensive proteins,
      phytohormones, and pro-/antioxidant status.

PMID- 21950111
TI  - [Antioxidant activity of oxygen-containing aromatic compounds].
AB  - Inhibition efficiency (antioxidant activity) of 26 oxygen-containing aromatic
      compounds was studied in methemalbumin-H202-o-phenylenediamine (PDA) or
      tetramethylbenzidine (TMB) pseudoperoxidase system at 20 degrees C in buffered
      physiological solution (pH 7.4) containing 6% DM F and 0.25% DMSO. The
      inhibitor's efficiency was quantitatively characterized by the inhibition
      constants (Ki, microM) or the inhibition degree (%). Ki values varied in the
      range of4 to 500 microM and were influenced by a substrate, the structure of an
      inhibitor, hydroxyl groups, electron-donating substituents in aromatic ring, and
      steric hindrances. The type of inhibition at cooxidation of eight pairs was
      noncompetitive, and that of five pairs was mixed and determined by the substrate
      nature and the inhibitor structure. Lignin phenolic compounds ofguaiacyl and
      syringal series exhibited high antioxidant activity (Ki in the range of 10-300
      microM), and their efficiency decreased in the following order: caffeic acid >
      synapaldehyde > syringic acid > coniferyl aldehyde > para-hydroxycou maric acid.

PMID- 21950112
TI  - [Identification of a new bioregulator acting in ultralow doses in bulb onion
      (Allium cepa L.)].
AB  - A bioregulator that has physicochemical and biological properties similar to a
      group of bioregulators isolated from various animal tissues has been found in the
      bulb onion (Allium cepa L.). It was determined that the biological action of the
      plant bioregulator is determined by a peptide with molecular weight of 4036 +/- 2
      Da whose 18-C-terminal amino acid sequence consisted of 18 residues. On models of
      seed germination of some vegetable cultures, the ability of the bioregulator
      isolated from supernatant of onion extract in ultralow doses (10(-13) mg of
      protein/ml) to inhibit growth and development was demonstrated.

PMID- 21950113
TI  - [Fragment of the gene encoding chymotrypsin and trypsin inhibitor protein of
      potato tubers].
AB  - Product of polymerase chain reaction designated as PKPIJ-B was isolated after
      amplification from genomic DNA of potato (Solarium tuberosum L., Zhukov Jubilee
      cultivar) using the designed primers. Nucleotide sequence of PKPIJ-B was
      determined and amino acid sequence of protein was restored. Analysis of this
      sequence has allowed us to suggest that isolated gene fragment encodes
      chymotrypsin and trypsin inhibitor protein (PKCI-23 potato Kunitz-type
      chymotrypsin inhibitor) of potato tubers.

PMID- 21950114
TI  - Over-expression, purification and functional characterization of Celosia ClpS as
      a fused protein in Escherichia coli.
AB  - A ClpS homologue from Celosia cristata was expressed as maltose-binding fusion
      protein under the control of strong inducible tac promoter of pMALc2X vector in
      TB 1 strain of Escherichia coli. SDS-PAGE analysis showed that fused ClpS is
      produced as about 63 kDa protein in recombinant bacteria. Expressed product was
      purified to homogeneity with a yield of about 31 mg/l of bacterial culture. The
      results indicated that heterologous expression of Celosia ClpS does not affect
      bacterial growth under different induced conditions. Total cellular antioxidant
      assessment results revealed that the induction of ClpS activates the bacterial
      antioxidative system. Since, the purified ClpS did not exhibit antioxidant
      activity in vitro, we speculated a functional corelation between bacterial
      protelolytic apparatus and its anti-oxidative system. This prediction may
      contribute to our better understanding of functional relationship between
      proteolytic and antioxidative systems in biological worlds in the future
      investigations.

PMID- 21950115
TI  - [Anaerobic synthesis of succinic acid by Escherichia coli strains with activated
      NAD+ reducing pyruvate dehydrogenase complex].
AB  - Effect of constitutive expression of the aceEF-lpdA operon genes coding for the
      enzymes of NAD+ reducing pyruvate dehydrogenase complex on the anaerobic
      production of succinic acids from glucose by recombinant Escherichia coli strains
      was studied. Basic producer strains were obtained by inactivation of the main
      pathways for synthesis of acetic and lactic acids by deletion of the genes ackA,
      pta, poxB, and ldhA (SGMO.1) in E. coli strain MG 1655 cells and additional
      introduction of the Bacillus subtilis pyruvate carboxylase (SG M0.1 [pPYC]). A
      constitutive expression of the genes aceEF-lpdA in derivatives of the basic
      strains SGM0.1 PL-aceEF-lpdA and SGM0.1 PL-aceEF-lpdA [pPYC] was provided by
      replacing the native regulatory region of the operon with the lambda phage PL
      promoter. Molar yields of succinic acid in anaerobic glucose fermentation by
      strains SGM0.1 P(L)-aceEF-lpdA and SGM0.1 PL-aceEF-lpdA [pPYC] exceeded the
      corresponding yields displayed by several control strains (exceeded considerably
      in the case of the strains with a pyruvate carboxylase activity). It is concluded
      that an increase in the succinic acid production by strain SGM0.1 PL-aceEF-lpdA
      [pPYC] as compared with the strains SGM0.1 and SGM0.1 [pPYC], which synthesize
      this substance in the reductive tricarboxylic acid cycle, is determined by
      activation of the glyoxylate shunt.

PMID- 21950116
TI  - Heterogenous expression of poly-gamma-glutamic acid synthetase complex gene of
      Bacillus licheniformis WBL-3.
AB  - Bacillus licheniformis WBL-3, one of poly-gamma-glutamic acid (gamma-PGA)
      producers, depends on the existence of glutamate in the medium. In this paper,
      gamma-PGA synthetase complex gene (pgsBCA) was cloned from Bacillus licheniformis
      WBL-3. pgsBCA gene of B. licheniformis WBL-3 was highly homologous with pgsBCA
      gene of B. licheniformis 14580. The similarity was 97%, but the similarity of
      pgsBCA gene between B. licheniformis WBL-3 and Bacillus subtilis IF03336 was only
      74%. However, when pgsBCA was expressed in Escherichia coli, the E. coli clone
      produced gamma-PGA extracellularly. The yield of gamma-PGA was 8.624 g/l. This
      result infers that B. licheniformis and B. subtilis has the similar gamma-PGA
      biosynthesis mechanism, namely, glutamic acid is catalyzed by an ATP-dependent
      amide ligase to synthesize gamma-PGA.

PMID- 21950117
TI  - [Transformation of delta4-3-ketosteroids by free and immobilized cells of
      Rhodococcus erythropolis actinobacterium].
AB  - 9alpha-Hydroxy derivatives were prepared from 11 steroids ofandrostane and
      pregnane series using Rhodococcus erythropolis VKPM Ac-1740 culture with 0.5-20
      g/l substrate concentration in the reaction mixture. 9alpha-Monohydroxylation
      proceeded regardless of the substituent structure at C17. However, the structure
      of the steroid molecule influenced the time of complete conversion of the
      substrate and the yield of the transformation product. 9alpha-Hydroxy
      androstenedione was obtained in 35 h in a yield of 85% when the maximum
      concentration of androstenedione (AD) was 10 g/l. 9alpha-Hydroxy-AD was also
      formed by the actinobacterium cells entrapped in poly(vinyl alcohol) cryogel
      beads. Nine successive transformation cycles were carried out using immobilized
      cells at 4.0 g/l concentration of AD in the medium. The yield of 9alpha-hydroxy
      AD formed during six cycles (from two to eight with the duration of each cycle
      for 22-24 h) was 98%.

PMID- 21950118
TI  - [Scaling of the process of biosynthesis of surfactants by Rhodococcus
      erythropolis EK-1 on hexadecane].
AB  - Peculiarities of synthesis of surface-active substances (SAS) are studied at
      periodical cultivation of Rhodococcus erythropolis EK-1 in the AK-210 fermenter
      on medium containing n-hexadecane. Maximum indicators of SAS synthesis
      (concentration of extra cellular SAS is 7.2 g/l; factor of emulsification of the
      cultural liquid 50%; SAS yield from the substrate 50%) have been observed at 60
      70% concentration of dissolved oxygen from the saturation level with aerial
      oxygen (pH 8.0) fractional supply of the substrate by portions each being 0.3
      0.4% every 5-6 h to a final volume concentration of 2.4% and with the use of 10%
      inoculate grown until mid-exponential phase on the medium with 1.0 vol % of n
      hexadecane. Implementation of the process of SAS biosynthesis with the
      fermentation equipment provided the possibility to increase almost two-fold the
      amount of the synthesized SAS and reduce 3.5-fold the time of cultivation of the
      producer strain compared with the growth in flasks at shake-flask propagator.

PMID- 21950119
TI  - [Chemiluminescence analysis of oil oxidizing bacteria Actinetobacter
      calcoaceticus extracts: effects of the extracts on pSoxS-lux biosensor].
AB  - A comparative H2O2-luminol- and Fe(II)-induced chemiluminescence analysis of
      extracts of two strains of marine oil oxidizing bacteria Actinetobacter
      calcoaceticus cultivated either in the presence or absence of oil was carried
      out. Effects of these extracts on E. coli MG1655 biosensor (pSoxS-lux) were
      studied. Activation of H2O2-induced chemiluminescence in the presence of oil was
      observed. This suggests activation of free radical lipid peroxidation. Aqueous
      extracts of microorganisms cultivated in the presence of oil were shown to
      activate reactive oxygen species production (ROS) in Fe(II)-induced
      chemiluminescence reaction mixture. Acetone-ethanol extracts induced
      antioxidative systems of both strains. Chemiluminescence analysis in a biological
      system carried utilizing E. coli MG1655 (pSoxS-lux) revealed that aqueous
      extracts of the strains cultivated in the absence of oil contained potential
      antioxidants.

PMID- 21950120
TI  - [Filamentous fungi's cell-wall extraction at different stages of ontogenesis and
      exploration of their carbohydrate composition].
AB  - Methods of obtaining cell walls (CW) for specimens of mucoraceous molds and
      ascomycetic affined fungi are developed at the stage of mycelium and resting
      cells, or spores. CW purity was assessed by electron microscopy, specific
      staining methods, scourage control, presence of ribose and desoxyribose, and the
      comparison of chitin content in whole cells and CW of fungi (a new criteria). The
      authors discuss the significance of the proposed methods of obtaining pure
      fractions of CW and of the study of their carbohydrate content for the
      chemotaxonomy of filamentous fungi.

PMID- 21950121
TI  - An extracellular glucoamylase produced by endophytic fungus EF6.
AB  - A strain of endophytic fungus EF6 isolated from Thai medicinal plants was found
      to produce higher levels of extracellular glucoamylase. This strain produced
      glucoamylase of culture filtrate when grown on 1% soluble starch. The enzyme was
      purified and characterized. Purification steps involved (NH4)2SO4 precipitation,
      anion exchange, and gel filtration chromatography. Final purification fold was
      14.49 and the yield obtained was 9.15%. The enzyme is monomeric with a molecular
      mass of 62.2 kDa as estimated by SDS-PAGE, and with a molecular mass of 62.031
      kDa estimated by MALDI-TOF spectrometry. The temperature for maximum activity was
      60 degrees C. After 30 min for incubation, glucoamylase was found to be stable
      lower than 50 degrees C. The activity decrease rapidly when residual activity was
      retained about 45% at 55 degrees C. The pH optimum of the enzyme activity was
      6.0, and it was stable over a pH range of 4.0-7.0 at 50 degrees C. The activity
      of glucoamylase was stimulated by Ca2+, Co2+, Mg2+, Mn2+, glycerol, DMSO, DTT and
      EDTA, and strongly inhibited by Hg2+. Various types of starch were test, soluble
      starch proved to be the best substrate for digestion process. The enzyme
      catalyzes the hydrolysis of soluble starch and maltose as the substrate, the
      enzyme had Km values of 2.63, and 1.88 mg/ml and Vmax, values of 1.25, and 2.54
      U/min/mg protein, and Vmax/Km values of 0.48 and 1.35, respectively. The internal
      amino acid sequences of endophytic fungus EF6 glucoamylase; RALAN HKQVV DSFRS
      have similarity to the sequence of the glucoamylase purified form Thermomyces
      lanuginosus. From all results indicated that this enzyme is a glucoamylase (1,4
      alpha-D-glucan glucanohydrolase).

PMID- 21950122
TI  - [Antioxidant components of Laetiporus sulphureus (Bull.: Fr.) Murr. fruit
      bodies].
AB  - Antioxidant activity of fruit bodies of Laetiporus sulphureus (Bull.: Fr.) Murr.
      (Polyporales) obtained by the natural plantation growing method in Pribaikal'e
      (Irkutsk region) has been studied. It was determined that the ethyl acetate
      fraction of L. sulphureus, which was chromatographically separated into seven
      compounds identified as quercetin, kaempferol, (+)-catechin, p-coumaric, gallic,
      caffeic, and chlorogenic acids was characterized with more expressed antioxidant
      activity. All compounds were extracted from this basidiomycete species for the
      first time. The quantitative amount of the substances isolated from L. sulphureus
      was determined by HPLC. It was found that antioxidant activity of preparations
      obtained from L. sulphureus is conditioned by phenolic compounds.

PMID- 21950123
TI  - [Physiological and biochemical characteristics of fungi of the genus Penicillium
      as producers of ergot alkaloids and quinocitrinins].
AB  - Four cultures of fungi of the genus Penicillium belonging to Furcatum Pitt
      subgenus, such as P. citrinum Thom, 1910; P. corylophilum Dierckx, 1901; P.
      fellutanum Biourge, 1923; and P. waksmanii Zaleski, 1927, produced the ergot
      alkaloids, namely, agroclavine-I, and epoxyagroclavine-I; their N-N-dimers, such
      as dimer of epoxyagroclavine-I and the mixed dimer of epoxyagroclavine-I and
      agroclavine-I; and also quinoline metabolites, namely, quinocitrinin A and
      quinocitrinin B. Physiological and biochemical characteristics of the producers
      were studied. Optimal conditions for the biosynthesis of metabolome components
      were determined. Zinc additive to the medium stimulated the biosynthesis of the
      ergot alkaloids in all cases; citrinin production was increased only in P.
      citrinum, and that was suppressed in P. corylophinum, P. fellutanum, and P.
      waksmanii. This testifies that genes of the biosynthesis pathways are located in
      the different clusters of the producers.

PMID- 21950124
TI  - [Influence of salicylic acid on biosynthesis of nucleic acids in Polyscias
      filicifolia cell culture under the action of unfavorable temperatures].
AB  - Amounts of DNA and RNA was increased (from 20 to 50%) in the presence of
      salicylic acid in cells of Polyscias filicifolia tissue culture grown in
      Murachige-Skoog modified medium. Treatment of the tissue culture with salicylic
      acid resulted in a significant increase of intracellular protein and decrease of
      proteolytic activity. In cells treated with salicylic acid, the amounts of DNA
      and RNA was higher in conditions of heat (3 h, 45 degrees C) and cold (24 h, 7
      degrees C) stress in comparison with cells exposed to unfavorable temperatures
      without the initial treatment with salicylic acid.

PMID- 21950125
TI  - [Effect of salicylic acid on the proton translocation activity of plasmalemma of
      potato tuber cells].
AB  - Action of salicylic acid (SA) on the activity of membrane bound H(+)-ATPase and
      passive proton permeability of plasmalemma membrane vesicles (PMV) from
      parenchyma cells of potato tubers was detected. A correlation between SA action
      and germination of tubers and activity of plasmalemma H(+)-ATPase was revealed:
      the application of growth-stimulating concentrations of SA (10(-10)-10(-8) M) in
      the system in vitro resulted in activation of plasmalemma H(+)-ATPase, while the
      utilization of growth-inhibiting concentrations (10(-4), 10(-5) M) provoked
      inhibition of the enzyme activity. Addition of jasmonic acid (JA) to the
      incubation mix resulted in increase of SA effect on the accumulation of H+ in
      PMV.

PMID- 21950126
TI  - [Effect of melafen on mitochondrial apparatus of apical meristem in growth
      regulation in potato tubers].
AB  - Growth stimulation in potato Solanum tuberosum L. tubers by melafen preparation
      caused an increase in area ofmitochondrial apparatus (increase in mitochondrial
      size) in apical meristem cells. Melafen stimulated mitochondrial differentiation
      (increase in number of condensed mitochondria enriched in cristas). Obtained data
      revealed an increase in activity of mitochondrial apparatus which is connected
      with an increase in energetic demands of cells in potato tuber apexes at melafen
      growth activation.

PMID- 21950127
TI  - [Oregano essential oil as an inhibitor of higher fatty acid oxidation].
AB  - Inhibition of the oxidation of fatty acids methyl esters by oregano essential oil
      was studied using capillary gas chromatography. A mixture of fatty acids which
      contained saturated, mono-, di-, and polyunsaturated acids with 16-24 carbon
      atoms was extracted from mice brain. Changes in the composition of esters in
      hexane solutions both in the presence of oregano essential oil and without it
      were examined during their autooxidation in light for 1 year. It was found that
      the oxidation rate of unsaturated fatty acids increases with increasing degree of
      their unsaturation. Oregano essential oil inhibited the oxidation process.
      Antioxidant activity of the oil increased with increase of its concentration. It
      was shown that carvacrol and thymol are the main antioxidant components of
      oregano oil.

PMID- 21950128
TI  - [Heat shock protein 90--modulator of TNFalpha-induced apoptosis of Jurkat tumor
      cells].
AB  - rTNFalpha-induced programmed death of Jurkat tumor cells cultured with 17-AAG, a
      selective inhibitor of heat shock protein (Hsp90), was studied by fluorescent
      microscopy with the use of FITC-labeled annexin V and propidium iodide. Caspase-3
      and -8 activities were determined by spectrophotometry using a caspase- 3 and -8
      colorimetric assay kit. It was shown that inhibition of Hsp90 leads to activation
      of Jurkat cell apoptosis while Hsp90 itself suppresses this process. 17-AAG
      enhances rTNFa-induced apoptosis of tumor cells.

PMID- 21950129
TI  - [Migration of 51Cr-labeled neutrophils to rat lungs after administration of
      glucoocorticoid kenalog].
AB  - Cells from the rat bronchoalveolar lavage fluid comprising over 70% of
      neutrophils were labeled with 51Cr and administered intraperitoneally or
      intravenously to control animals and to rats which were injected subcutaneously
      with 2 mg of ketalog 5 days before the onset of experiment. Blood samples, lung,
      hepatic, splenic, renal, small intestinal, and muscular biposies were taken 1
      hour after cell infusion. The intraperitoneal administration of 51Cr-labeled
      neutrophils did not significantly increase the radioactivity count rate in any
      organ examined. The rise was most notable in the lungs after v/v infusion of
      labeled neutrophils. Rats given kenalog showed a low level of radioactivity in
      the lung tissue compared with controls probably because the glucocorticoid caused
      a specific change in the mechanism of uptake of labeled neutrophils.

PMID- 21950130
TI  - [Disorders of psychoneurohumoral interrelations in patients suffering from
      arterial hypertension].
AB  - To elucidate disorders of psychoneurohumoral relationships in patients with grade
      I-II arterial hypertension at low, moderate and high overall cardiovascular risk,
      we measured body mass index, activity of sympathetic nervous system, serum leptin
      level and performed psychological tests aimed to elucidate situational and
      personal anxiety, aggressiveness and hostility. The data obtained allow a patient
      to be referred to one of the three possible types of disturbed psychoneurohumoral
      interrelations, viz. anxiety-metabolic, anxiety-adrenergic, and aggressive
      metabolic, each having its own specific gender-related and clinical features.
      Discrimination between these types permits to substantiate pathogenetic therapy
      of arterial hypertension on an individual basis.

PMID- 21950131
TI  - [Knowledgebase as a tool for monitoring post-genomic medico-biological research].
AB  - On-going molecular biological researches are characterized by exponential
      increase in the amount of experimental data which dictates the necessity to
      develop relevant information technologies. The knowledge-based approach appears
      to be a most promising and flexible tool for analytical processing biomedical
      information that allows new relationships between study objects to be
      established. In this article we analyze the work of researchers based at the
      Institute of Biomedical Chemistry with the materials of the PubMed biomedical
      library. A list of publication IDs for a half-year period has been compiled to
      elucidate individual profiles of research activities. Statistical analysis of
      medical subject headings (MeSH) reveals typical profiles of research of interest
      for separate divisions of the Institute. The proposed approach may be recommended
      as a means for improving the efficiency and coordination of biomedical research.

PMID- 21950132
TI  - [Regulatory T-cells: modern approaches to optimization of their numbers].
AB  - Regulatory T-cells (Tregs) are important components of the complex adaptive
      system of the body responsive to environmental challenges. Tregs ensure
      peripheral tolerance and play an important role in control of inflammatory
      reactions. Several subsets of Tregs have been described. Naturally occurring
      CD4+CD25+ Tregs are recognized as a major subset of immune cells responsible for
      peripheral immune self-tolerance. Another subtype of Tregs is inducible. Such
      Tregs are generated in the periphery and realize their suppressive potential
      largely in the form of anti-inflammatory activity. The latter plays an important
      role in cooperation of three principal anti-inflammatory mechanisms that
      developed in the course of evolution: macrophages possessed of suppressive
      activity, Tregs, and stress hormones. Normally, all the three mechanisms of
      inflammation control are in equilibrium. However, the balance may be disturbed
      with ageing due to repeated episodes of stress and HPA axis activation. As a
      result, secretion of stress hormones coupled to antigen overload leads to Treg
      accumulation. In the course of time activation of the HPA axis is replaced by its
      inhibition manifested both as a decrease of the baseline cortisol level and a
      reduction of stress-induced cortisol response. Cortisol present in blood at low
      concentrations is no longer capable of controlling inflammation and Tregs become
      a principal mechanism of anti-inflammatory machinery. Superfluous Treg
      accumulation results in the development of functional somatic syndromes, such as
      chronic fatigue syndrome, and (in some patients) in the growth of tumours
      resulting from the suppression of anticancer immunity. On the other hand, the
      lack of adequate antigen loading in the childhood may delay Treg maturation.
      Allergy and asthma manifestations may be a consequence of such Treg
      insufficiency. Thus, both excess and deficiency of Tregs may be at the bottom of
      morbid conditions. The advances in modern pharmacology open up opportunities for
      developing new methods to control the Treg level.

PMID- 21950133
TI  - [Adaptive hypometabolism in man].
AB  - Two hypotheses of functional organization of hypoxic hypometabolism in man is
      discussed. One is a bioenergetic hypothesis stating that progressive oxygen
      deficiency in the cells leads to suppression of macrophage production. The other
      regards hypometabolism as a result of decreased energy consumption in response to
      hypoxia or the lack of energy of any etiology; it results in impaired intensity
      of energy metabolism. The letter strategy is underlain by central regulatory
      mechanisms for which proteins of the HIF-factor system are the most probable
      markers.

PMID- 21950134
TI  - [Dmitri Dmitrievich Yablokov, an outstanding representative of Russian
      therapeutic school].
AB  - A short biography and major scientific publications of Dmitri Dmitrievich
      Yablokov (1896-1993), member of the Russian Academy of Medical Sciences and an
      outstanding representative of the Tomsk therapeutic school, are presented.

PMID- 21950135
TI  - [120th anniversary of F.F.Erisman Federal Research Centre for Hygiene].
AB  - F.F.Erisman Federal Research Center for Hygiene is a leading hygienic scientific
      centre of the Federal Service for Supervision in the Field of Consumer Rights
      Protection and Human Well-Being widely known in this country and abroad. The
      history of FRCH can be arbitrarily divided into the following three periods:
      prerevolutionary (1891-1917), Soviet (1917-1991), and modern (1991-the present
      time). The first period is the time of life and work of Fyedor Fyedorovich
      Erisman, professor of Moscow University and the founder of scientific hygiene in
      Russia. The second period is characterized by realization of F.F.Erisman's ideas
      based on achievements in biology, natural and experimental studies. The third
      period is associated with the name of professor A.I. Potapov, member of the
      Russian Academy of Medical Sciences. His authority, scientific experience, and
      organizational work made it possible to come out with credit of a most difficult
      situation in Russian science. Scientific, historical and staff-related issues are
      considered.

PMID- 21950137
TI  - [Molecular genetic analysis of soriz genome (Sorghum oryzoidum)].
AB  - Molecular-genetic analysis of soriz genotypes (Sorghum oryzoidum), its paternal
      form Sorghum bicolor (L.) Moench (grain sorghum), possible parents (Sorghum
      sudanense (Piper.) Stapf. (Sudan grass) and Oryza sativa L. (rice planting)) and
      the nearest relatives has been carried out using microsatellite (MS) loci of
      sorghum and rice. Based on these data genetic distances have been calculated. It
      was shown that soriz do not bear DNA fragments of rice, but contains in its
      genome DNA fragments belonging to the Sudanese grass indicating that the origin
      of soriz is associated with Sorghum sudanense.

PMID- 21950136
TI  - [Peculiarities of urinary bladder cancer tumor cells apoptosis response on
      neoadjuvant chemotherapy].
AB  - Induced apoptosis in urinary bladder cancer tumor cells of patients was studied
      using TUNEL reaction. It was shown that increase in induced apoptosis value had a
      definite correlation between corresponding features of tumor reaction as a
      response on Gemcitabine-Cisplatin neoadjuvant chemotherapy application. It was
      found that evaluation of induced apoptosis in urinary bladder cancer tumor cells
      using TUNEL method allows forecasting the effectiveness of chemotherapy on the
      cellular level in patients with this type of cancer.

PMID- 21950138
TI  - [Study of interaction of wild soybean subpopulations (Glycine soja) in the valley
      of the Tsukanovka river in the south of Far East of Russia].
AB  - A comparative study of the genetic structure of natural and anthropogenic
      populations of G. soja gives significant information about formation of different
      populations, and allows developing measures for preservation of unique natural
      gene bank of wild soybean, the species closely related to cultivated soybean. In
      this study, ISSR markers were used to carry out a comparative analysis of genetic
      structure of natural and anthropogenic subpopulations of G. soja for studying
      possible mutual influence of subpopulations of anthropogenic and natural
      phytocenosis on the formation of their genetic diversity and to study genetic
      structure of natural subpopulations of wild soybean in the contact places between
      the two types ofcenoses. As a result, the characteristics that describe the
      genetic diversity of studied populations have been identified and the important
      role of an interaction between subpopulations of different phytocenoses on
      formation of the spatial genetic structure of population in the valley of
      Tsukanovka river has been demonstrated.

PMID- 21950139
TI  - [Genoprotective activities of the oils from leaves and fruits of Fagus orientalis
      Lipsky].
AB  - The antimutagenic activities of the oils obtained from leaves and fruits of Fagus
      orientalis have been shown in experiments with spontaneous and mutagen- and
      ageing-induced variability. The aberrations of chromosomes in the meristematic
      cells of the Allium cepa L., Vicia faba L., Triticum aestivum L., and marrow
      cells of Vistar rats as well as Arabidopsis thaliana gene mutations have been
      mobilized as experimental tests.

PMID- 21950140
TI  - [Relationship of TLR2 and TLR4 gene polymorphism with a penchant for individual
      urogenital infections].
AB  - We investigated the population prevalence of polymorphisms of Arg753Gln TLR2gene,
      and Asp299Gly, Thr399Ile TLR4 genes among people living in the Poltava region, as
      well as data communication polymorphisms with the presence of diseases caused by
      urogenital infections. The group of population control was a random sample of
      residents of the Poltava region (n = 299). The group of patients with urogenital
      diseases included 156 people. Genotyping of these groups TLR2 Arg753Gln
      polymorphism and the gene TLR4 Asp299Gly, Thr399Ile was performed using PCR and
      subsequent restriction analysis. Statistically significant association of allele
      A ofgene TLR2 (p = 0.0018) and allele G of gene TLR4 (p = 0.085) with the
      presence of urogenital diseases was confirmed.

PMID- 21950141
TI  - [The chiral mutagens: cytogenetic effects on higher plants].
AB  - The paper covers investigation of cytogenetic activity of chiral mutagens and
      their specific effects on the plant cells chromosomes of soft winter wheat
      (Triticum aestivum L.). Comparative analysis of cytogenetic activity of chiral
      NEU: S(+)1-N-nitroso- 1-N-methyl-3-N-sec-buthylureas (S(+)NMsBU) and R(-)1-N
      nitroso- 1N-methyl-3-Nsec-buthylureas (R(-)NMsBU) on winter wheat was performed.
      As it was shown by the frequency of chromosomal aberrations the S(+) stereoisomer
      was twice more active than R(-). In addition to typical anaphase aberrations
      (fragments, bridges, lagging chromosomes) the numerous mitosis pathologies were
      revealed - K-mitoses, hyperspiralization and despiralization of chromosomes,
      unequal allocation of chromosomes between the daughter nuclei, mass
      fragmentation, nondisjunction and chromosome adhesion, three-pole mitoses, etc.
      Neither of the mentioned pathologies was observed under the action of NEU and
      gamma-rays.

PMID- 21950142
TI  - EMS-induced cytomictic variability in safflower (Carthamus tinctorius L.).
AB  - Seeds of safflower (Carthamus tinctorius L.) were subjected to three treatment
      durations (3h, 5h and 7h) of 0.5 % Ethyl Methane Sulphonate (EMS).
      Microsporogenesis was carried out in the control as well as in the treated
      materials. EMS treated plants showed interesting feature of partial inter
      meiocyte chromatin migration through channel formation, beak formation or direct
      cell fusion. Another interesting feature noticed during the study was the fusion
      among tetrads due to wall dissolution. The phenomenon of cytomixis was recorded
      at nearly all the stages of microsporogenesis connecting from a few to several
      meiocytes. Other abnormalities such as laggards, precocious movement, bridge and
      non-disjunction of chromosomes were also recorded but in very low frequencies.
      The phenomenon of cytomixis increased along with the increase in treatment
      duration of EMS. Cells with these types of cytomictic disturbances may probably
      result in uneven formation of gametes or zygote, heterogenous sized pollen grains
      or even loss of fertility in future.

PMID- 21950143
TI  - [Studi "priming" callose accumulation in Allium cepa when processing biotic
      inducers].
AB  - Effect of salicylic and caproic acids as an inducters of plant resistance was
      studied using three onion cultivars differed in resistance to Botrytis spp.
      Salicylic and caproic acids were shown to prime callose accumulation in Allium
      cepa varieties resistant to B. allii and B. cinerea. The results obtained sugest
      that protection of onion against necrotrophs involves the priming of callose
      accumulation which is important mechanical barrier against invading pathogens.

PMID- 21950144
TI  - [Genetic bases and functioning of plant signal transduction at virus resistance].
AB  - Recent insights into virus-host interaction have been compiled in this review,
      focusing on the genetic basis and the modern conception of the molecular
      mechanisms of pathogen (mostly viral) recognition by plants. The significance of
      plant signal transduction systems and their key factors are discussed. The
      possible role of different elicitors in signal transduction processes has been
      considered.

PMID- 21950145
TI  - [Gibberellin signaling pathways in plants].
AB  - During the last decade plant growth and development have been investigated at the
      molecular level. Plant specific family GRAS-proteins plays one of the key roles
      in the molecular mechanisms of this process. In this report we highlight the
      importance of DELLA-proteins and show the model ofgibberellin signalling pathway
      in plants that starts from the binding of biologically active gibberellic acid
      with receptor and DELLA-protein. This complex stimulates ubiquitination and
      degradation of DELLA-proteins through the proteasome pathway. After degradation
      of DELLA-proteins the repression of plant growth stops that allows gibberellin
      response to occur. The role of DELLA-proteins as transcription factors is
      discussed.

PMID- 21950146
TI  - Dose-dependent pharmacokinetics of tyrosol galactoside as an anti-fatigue drug in
      rats.
AB  - Tyrosol galactoside (TG) is a new candidate anti-fatigue agent under development.
      In order to have a good understanding of its pharmacokinetic characters, the
      paper describes the dose-dependent pharmacokinetics of TG in rats after oral and
      intravenous administration. TG was rapidly absorbed after oral administration and
      cleared with first-order rate, for the plasma half-life was independent of dose.
      C(max) and AUC(0-infinity) after both intravenous and oral dosing were all
      linearly correlated with the dose, as the regression correlation coefficient (R)
      was 0.998, 0.989 and 0.994 for AUC(0-infinity) (i.v., P < 0.01) AUC(0-infinity)
      (i.g., P < 0.01) and C(max) (i. g., P < 0.01), respectively. However, these
      parameters increased less than proportionally with increasing dose. In addition,
      the apparent volume of distribution (Vd) and the apparent clearance (Cl) seemed
      to be affected by the dose.

PMID- 21950147
TI  - Fasted state bioavailability of two delayed release formulations of divalproex
      sodium in healthy Iranian volunteers.
AB  - The purpose of this study was to compare the pharmacokinetics and bioavailability
      of two commercial brands of delayed release divalproex sodium (CAS 76584-70-8)
      tablets in healthy male Iranian volunteers in fasted state. Each single-dose,
      randomized, open-label, blind study was conducted according to a crossover design
      in subjects. A washout interval of 14 days separated the doses in each study.
      Serial venous blood samples were obtained over 24 h after each administration to
      measure drug in serum, and placed into tubes containing sodium heparin. Then the
      separated plasma was kept frozen at -20 degrees C for subsequent analysis. The
      plasma concentrations of drug were analyzed by a validated sensitive HPLC method
      with UV detection. Mean maximum serum concentrations of 124.5 +/- 34.8 microg/ml
      and 134.2 +/- 31.1 microg/ml were obtained for the test and reference products,
      respectively. The AULo(t) and AUCo(infinity) were 2023.8 +/- 578.8 1 microg h/ml
      and 2705.3 +/- 792.1 microg h/ml for the test and 2068.2 +/- 526.4 microg h/ml
      and 2729.6 +/- 698.2 microg h/ml for the reference formulation, respectively. The
      calculated 90% confidence intervals for the ratio of C(max) (87.2-101.5%),
      AUCo(t) (92.1-108.6%) and AUCo(infinity) (93.1-110.6%) values for the test and
      reference products were all within the 85-120% interval proposed by the FDA and
      EMA. Therefore the divalproex sodium tablets of the test and reference products
      are bioequivalent in terms of rate and extent of absorption.

PMID- 21950148
TI  - Pharmacokinetics of felodipine extended-release tablets in healthy Taiwanese
      subjects: a retrospective review.
AB  - The objective of this study was to investigate the pharmacokinetics of felodipine
      (CAS 72509-76-3) in healthy male Taiwanese subjects. This is a retrospective
      review of five felodipine pharmacokinetic studies completed in Taiwan. A total of
      100 evaluable healthy Taiwanese males were enrolled in these studies. The
      subjects received 5 mg (n = 80) or 10 mg (n = 20) of Plendil (felodipine extended
      release tablets; felodipine ER) once daily for 6 days. The mean +/- SD t(max,ss,)
      CG(max,ss) and AUG(tau) of dose normalized to 10 mg felodipine was 3.32 +/- 1.33
      h, 13.12 +/- 5.34 nmol/L and 136.33 +/- 63.18 nmol x h/L, respectively. By using
      Kolmogorov-Smirnov's test and probit plots, the results indicated that the
      frequency distribution of AUC/dose, C(min)/dose and CL/F was bimodal. Compared to
      data from the literature, the mean C(max,ss) and AUG(tau) of 5 mg felodipine in
      healthy young Taiwanese subjects were similar to or slightly lower than data from
      Swedish, Danish, Turkish and Canadian studies in healthy young subjects who
      received 10 mg felodipine. Comparable C(max) values and approximately 30% lower
      AUC values were observed when comparing the 5 mg Taiwanese data to data in
      healthy elderly German subjects who also received 5 mg felodipine. Taiwanese
      subjects might have lower CYP3A4 activity to metabolize felodipine, which is
      similar to the phenomenon observed with nifedipine.

PMID- 21950149
TI  - Synthesis and antihyperlipidemic activity of some novel 4-(substitutedamino)-5
      substituted-3-mercapto- (4H)-1,2,4-triazoles.
AB  - Hyperlipidemia is considered one of the key factors for cardiovascular diseases.
      Based on earlier work on a series of 5-alkyl-4-aryl-3-mercapto-(4H)-1,2,4
      triazoles, for further lead modification, a series of 4-(substituted)amino-5
      substituted-3-mercapto-(4H)-1,2,4-triazoles was designed. Target compounds were
      synthesized by the well known Hoggarth synthesis of substituted 1,2,4-triazoles.
      Synthesized compounds were screened for lipid lowering activity using the
      "Poloxamer 407 induced hyperlipidemia in rats" model at a dose of 100 mg/kg p.o.
      Compounds were found to alter serum lipid levels significantly. Most of the
      compounds significantly reduced serum cholesterol and triglyceride levels. Some
      of the compounds were found to reduce triglycerides and elevate high density
      lipoprotein (HDL) levels more than the standard drug atorvastatin (CAS 134523-03
      8). Compounds with chloro substitution on aryl rings were found more active in
      reducing serum lipid levels than other substitutions.

PMID- 21950150
TI  - Investigation of the unique metabolic fate of ethyl (6R)-6- [N- (2-chloro-4
      fluorophenyl) sulfamoyl] cyclohex-1-ene-1-carboxylate (TAK-242) in rats and dogs
      using two types of 14C-labeled compounds having different labeled positions.
AB  - The pharmacokinetics of TAK-242 (ethyl (6R)-6- [N-(2-chloro-4
      fluorophenyl)sulfamoyl]cyclohex-1-ene-1-carboxylate, CAS 243984-11-4) and its
      metabolites were investigated in rats and dogs after intravenous (i.v.) dosing of
      TAK-242 using two types of radiolabeled TAK-242: [phenyl ring-U-14C]TAK-242 and
      [cyclohexene ring-U-14C]TAK-242. The phenyl ring moiety of TAK-242 yielded 2
      chloro-4-fluoroaniline, M-I, and M-I was further acetylated and conjugated to
      form M-II and the glucuronide (M-I-G), respectively. M-I was also converted to M
      III and M-IV by hydroxylation and subsequent sulfate conjugation. Meanwhile, the
      cyclohexene ring moiety of TAK-242 was metabolized to glutathione conjugate, M
      SG, followed by further metabolism of M-SG to form cysteine conjugate (M-Cys) and
      mercapturic acid conjugate (M-Mer). After i.v. injection of [phenyl ring-U
      14C]TAK-242 to rats and dogs, the 14C concentrations in dogs declined slowly with
      a half-life of about 1 week although that in rats was about 6 h. The predominant
      components in the plasma of rats and dogs were M-I-G and M-III, respectively.
      After i.v. injection of [cyclohexene ring-U-14C]TAK-242 to rats and dogs, 14C
      components unextractable by organic solvents were observed in the plasma. These
      results indicated two unique metabolic fates of TAK-242. The phenyl ring moiety
      of TAK-242 showed species differences between rats and dogs in the metabolism and
      excretion kinetics and the cyclohexene ring moiety of TAK-242 showed potential
      for covalent binding to endogenous components such as plasma proteins.

PMID- 21950151
TI  - Preparation of ciprofloxacin-coated zinc oxide nanoparticles and their
      antibacterial effects against clinical isolates of Staphylococcus aureus and
      Escherichia coli.
AB  - In the present research study, ciprofloxacin-coated zinc oxide nanoparticles were
      prepared using a precipitation method. The nature of interactions between zinc
      oxide nanoparticles and ciprofloxacin (CAS 85721-33-1) was studied by Fourier
      transform infrared spectroscopy. The results show that the carbonyl group in
      ciprofloxacin is actively involved in forming chemical--rather than physical-
      bonds with zinc oxide nanoparticles. Also the antibacterial activity of free zinc
      oxide nanoparticles and ciprofloxacin-coated zinc oxide nanoparticles have been
      evaluated against different clinical isolates of Staphylococcus aureus and
      Escherichia coli. The free zinc oxide nanoparticles did not show potent
      antibacterial activity against all test strains. In contrast, only the low
      concentrations of ciprofloxacin-coated zinc oxide nanoparticles (equivalent to
      the sub-minimum inhibitory concentrations of pure ciprofloxacin) considerably
      enhanced the antibacterial activity of zinc oxide nanoparticles against different
      isolates of Staphylococcus aureus and Escherichia coli (4 to 32 fold increase).
      The result is of particular value, since it demonstrates that, by using
      biocompatible zinc oxide nanoparticles in combination therapy, lower amounts of
      antibiotics may be needed.

PMID- 21950152
TI  - Rapid high-performance liquid chromatographic method for determination of
      adefovir in plasma using UV detection: application to pharmacokinetic studies.
AB  - A rapid, sensitive and reproducible HPLC method was developed and validated for
      the analysis of adefovir (CAS 106941-25-7) in human plasma. The separation was
      achieved on a monolithic silica column (Chromolith Performance RP-18e, 100 x 4.6
      mm) using acetonitrile-ammonium dihydrogen phosphate buffer (6:94, v/v), pH 5.2,
      as the mobile phase at a flow rate of 1.5 ml min(-1). The wavelength was set at
      260 nm. The assay enables the measurement of adefovir for therapeutic drug
      monitoring with a minimum quantification limit of 1 ng ml(-1). The method
      involves a simple protein precipitation procedure. Analytical recovery was
      complete. The calibration curve was linear over the concentration range 1-40 ng
      ml(-1). The coefficients of variation for inter-day and intra-day assay were
      found to be less than 5%. The method was applied to the determination of adefovir
      in plasma from 12 subjects dosed with adefovir 2 x 10 mg tablets and
      pharmacokinetic parameters were evaluated.

PMID- 21950153
TI  - Bioequivalence study of two oral tablet formulations containing saquinavir
      mesylate boosted with ritonavir in healthy male subjects.
AB  - Saquinavir (SAQ) mesylate (CAS 149845-06-7) is a potent inhibitor of the HIV-1
      protease indicated in combination with other antiretrovirals for the management
      of HIV-1 infection. The objective of this study was to compare rate and extent of
      absorption and to assess the bioequivalence between a new pharmaceutical
      equivalent tablet formulation containing 500 mg of SAQ mesylate and the innovator
      film coated tablet formulation. A randomized, single-center, open-label, two
      treatment, two-sequence, three-period, replicated crossover bioequivalence study
      in 40 healthy male subjects was conducted. All subjects received 100 mg ritonavir
      (CAS 155213-67-5) twice daily for a run-in period of 3 days before treatment.
      Dosing was separated by a wash-out period of 14 days. Blood samples were
      collected over 72 h and plasma levels of SAQ were determined by a validated
      HPLC/UV assay. The 90% confidence interval (CI) of the ratio of the geometric
      means for log-transformed C(max), AUC(last) and AUC(inf) values were used to
      assess bioequivalence using the equivalence interval of 80-125%. Point estimate
      and 90% CI of the ratios of C(max), AUC(last) and AUC(inf) values were 94.9 (80.9
      111.3), 97.4 (82.4-115.4) and 97.4 (82.5-115.0), respectively. Both treatments
      exhibited similar tolerability and safety. It was concluded that the new
      pharmaceutical product was bioequivalent to the innovator.

PMID- 21950155
TI  - Characterization of the fatty acid composition of Nannochloropsis salina as a
      determinant of biodiesel properties.
AB  - Nannochloropsis salina was cultured batch-wise to evaluate the potential of the
      alga to produce biodiesel. The cells were harvested at the end of the exponential
      growth phase when the concentration was 18 x 10(6) cells/mL culture. The growth
      estimated as dry weight from this cell number was (3.8 +/- 0.7) mg/L. The lipid
      and triglyceride contents were 40% and 12% on a dry weight basis, respectively.
      The amount of the ratio triglycerides/total lipids was approximately 0.3. The
      composition of triglyceride fatty acid methyl esters (biodiesel) was analysed by
      gas-liquid chromatography and identified as: C14:0, C16:0, C16:1, C18:0, C18:1,
      C18:2, C18:3, C20:1, and C20:5. The ratio of unsaturated to saturated fatty acid
      contents was approximately 4.4. Additionally, the characterization of each
      individual fatty acid ester was discussed with regard to the fuel properties of
      biodiesel produced by the alga.

PMID- 21950154
TI  - Quantification of polyacetylenes in apiaceous plants by high-performance liquid
      chromatography coupled with diode array detection.
AB  - Polyacetylenes are known for their biofunctional properties in a wide range of
      organisms. In the present study, the most frequently occurring polyacetylenes,
      i.e. falcarinol, falcarindiol, and falcarindiol-3-acetate, were determined in six
      genera of the Apiaceae family. For this purpose, a straightforward and reliable
      method for the screening and quantification of the polyacetylenes using high
      performance liquid chromatography coupled with diode array and mass spectrometric
      detection without tedious sample clean-up has been developed. Peak assignment was
      based on retention times, UV spectra, and mass spectral data. Quantification was
      carried out using calibration curves of authentic standards isolated from turnip
      rooted parsley and Ligusticum mutellina, respectively. The references were
      unambiguously identified by Fourier transform-IR (FT-IR) spectroscopy, GC-MS,
      HPLC-MSn in the positive ionization mode, and 1H NMR and 13C NMR spectroscopy. To
      the best of our knowledge, the occurrence of falcarindiol-3-acetate in Anthriscus
      sylvestris and Pastinaca sativa has been reported for the first time. The data
      revealed great differences in the polyacetylene contents and varying proportions
      of individual compounds in the storage roots of Apiaceous plants. The results of
      the present study may be used as a suitable tool for authenticity control and
      applied to identify novel sources devoid or particularly rich in polyacetylenes,
      thus facilitating breeding programs for the selective enrichment and depletion of
      these plant secondary metabolites, respectively.

PMID- 21950157
TI  - Antimicrobial evaluation of indole-containing hydrazone derivatives.
AB  - There has been an increasing importance of drug-resistant pathogens in clinical
      microbiological and antibacterial research. Indoles and hydrazone-type compounds
      constitute important classes of compounds in the search for effective agents
      against multidrug-resistant microbial infections. In this study a series of 1
      methylindole-3-carboxaldehyde hydrazone derivatives were evaluated for their in
      vitro antimicrobial activities using the two-fold serial dilution technique
      against Staphylococcus aureus, methicillin-resistant S. aureus, methicillin
      resistant S. aureus isolate, Escherichia coli, Bacillus subtilis, and Candida
      albicans. The minimum inhibitory concentration (MIC) of the test compounds and
      the reference standards sultamicillin, ampicillin, fluconazole, and ciprofloxacin
      was determined. All compounds possessed a broad spectrum of activity having MIC
      values of 6.25-100 microg/ml against the tested microorganisms. Aromaticity and
      disubstitution of the phenyl ring with especially fluorine and chlorine atoms
      were found to be significant for the antimicrobial activity

PMID- 21950156
TI  - Synthesis and in vitro study of antiviral and virucidal activity of novel 2-[(4
      methyl-4H-1,2,4-triazol-3-yl)sulfanyl]acetamide derivatives.
AB  - 2-[(4-Methyl-4H-1,2,4-triazol-3-yl)sulfanyl]acetamide derivatives were
      synthesized and their structures were confirmed by 1H NMR, IR, and elemental
      analysis. Cytotoxicity of the compounds towards HEK-293 and GMK cells was
      evaluated. Moreover, the antiviral and virucidal activities of these compounds
      against human adenovirus type 5 and ECHO-9 virus were assessed. Some of the newly
      synthesized derivatives have the potential to reduce the viral replication of
      both tested viruses.

PMID- 21950158
TI  - Fluorinated s-triazinyl piperazines as antimicrobial agents.
AB  - A series of 1,3,5-triazine derivatives that contain 4-amino-2-trifluoromethyl
      benzonitrile, 8-hydroxyquinoline, and different piperazines as substituents at
      the carbon atoms of the triazine ring have been synthesized by a simple and
      efficient synthetic protocol. The chemical structures of the compounds were
      elucidated with the aid of IR, 1H NMR and 13C NMR spectroscopy, and elemental
      analysis. The antimicrobial activity of the compounds was tested against seven
      bacteria (Staphylococcus aureus MTCC 96, Bacillus cereus MTCC 619, Escherichia
      coli MTCC 739, Pseudomonas aeruginosa MTCC 741, Klebsiella pneumoniae MTCC 109,
      Salmonella typhi MTCC 733, Proteus vulgaris MTCC 1771) and four fungi
      (Aspergillus niger MTCC 282, Aspergillus fumigatus MTCC 343, Aspergillus clavatus
      MTCC 1323, Candida albicans MTCC 183). The results indicate that some of the
      novel s-triazines have noteworthy activity in minimum inhibitory concentration as
      well as agar diffusion tests.

PMID- 21950159
TI  - Pharmacological activity of (R)-(+)-pulegone, a chemical constituent of essential
      oils.
AB  - (R)-(+)-Pulegone is a monoterpene found in essential oils from plants of the
      Labiatae family. This compound is a major constituent of Agastache formosanum
      oil. In this study, the effect of (R)-(+)-pulegone on the central nervous system
      was evaluated. (R)-(+)-Pulegone caused a significant decrease in ambulation and
      an increase in pentobarbital-induced sleeping time in mice, indicating a central
      depressant effect. (+)-Pulegone also significantly increased the latency of
      convulsions as assessed by the pentylenetetrazole (PTZ) method. The
      antinociceptive properties of this monoterpene were studied in chemical and
      thermal models of nociception. Chemical nociception induced in the first and
      second phase of the subplantar formalin test was significantly inhibited by (R)
      (+)-pulegone and was not blocked by naloxone. Thermal nociception was also
      significantly inhibited while (R)-(+)-pulegone increased the reaction latency of
      the mice in the hot plate test. These results suggest that (R)-(+)-pulegone is a
      psychoactive compound and has the profile of an analgesic drug.

PMID- 21950160
TI  - Antileishmanial and antitrypanosomal activity of triterpene derivatives from
      latex of two Euphorbia species.
AB  - The in vitro activity on Leishmania infantum promastigotes and Trypanosoma cruzi
      epimastigotes of 25 semisynthetic terpenoid derivatives has been evaluated. These
      compounds were obtained through chemical modifications of the major components of
      Euphorbia resinifera (alpha-euphol and alpha-euphorbol) and Euphorbia officinarum
      (obtusifoliol and 31-norlanosterol). Leishmaniasis and Chagas' disease are major
      worldwide health problems. The drugs of choice for their treatment are still
      problematic in both cases, and therefore there is an urgent need to discover new
      drugs with high activity and low side effects. Natural products have become a key
      source of new drugs in the last years. The genus Euphorbia has been the subject
      of abundant phytochemical and pharmacological research because of its potential
      medical applications, but the antiparasitic effects of derivatives from plants of
      this genus are still unknown. Our results showed that 76% and 64% of the test
      compounds had antiparasitic effects on L. infantum and T cruzi, respectively. The
      different activities on both parasites, especially their moderate effects on
      mammalian cells, indicate an interesting selective toxicity.

PMID- 21950161
TI  - Antitumour and antioxidant activity of some Red Sea seaweeds in Ehrlich ascites
      carcinoma in vivo.
AB  - The antitumour activities of extracts from the Red Sea seaweeds Jania rubens,
      Sargassum subrepandum, and Ulva lactuca were investigated in an in vivo mice
      model based on intramuscular injection of Ehrlich ascites tumour cells. In
      parallel, antioxidant activities were measured. Tumour marker levels, liver
      biochemical parameters, and hepatic oxidant/antioxidant status were measured to
      prove the anticancer and antioxidant nature of the algal extracts. Significant
      decreases in carcinoembryonic antigen (CEA) and a-fetoprotein (AFP) levels,
      activities of liver enzymes, levels of nitric oxide (NO) and malondialdehyde
      (MDA), and an increase in total antioxidant capacity (TAC) were recorded in
      groups treated with the algal extracts. Jania rubens was selected for
      phytochemical screening of its phytoconstituents. In addition, carotenoids,
      halides, minerals, lipoidal matters, proteins, and carbohydrates were studied.
      Furthermore, 7-oxo-cholest-5(6)-en-3-ol (1) and cholesterol (2) were isolated
      from the dichloromethane fraction.

PMID- 21950162
TI  - Liriodenine, early antimicrobial defence in Annona diversifolia.
AB  - Annonaceae aporphine alkaloids, of which liriodenine is the most abundant, have
      not been extensively studied from a biological standpoint. The goal of this study
      was to investigate the role of liriodenine in antimicrobial defense during early
      developmental stages in Annona diversifolia. The fungi Rhizopus stolonifer and
      Aspergillus glaucus, which are responsible for seed deterioration, were isolated
      during imbibition, and their antifungal activity was determined by diffusion,
      macrodilution, and metabolic inhibition assays using purified liriodenine and
      alkaloid extracts obtained from embryos, radicles, and roots at early
      developmental stages. The presence of liriodenine in extracts was quantified by
      high-performance liquid chromatography. Purified liriodenine and alkaloidal
      extracts inhibited both fungi, and there was a positive relationship between
      extract activity and amount of liriodenine contained therein. The quantity of
      liriodenine present in extracts suggests its importance in controlling other
      phytopathogens.

PMID- 21950163
TI  - Secondary metabolites of ponderosa lemon (Citrus pyriformis) and their
      antioxidant, anti-inflammatory, and cytotoxic activities.
AB  - Column chromatography of the dichloromethane fraction from an aqueous methanolic
      extract of fruit peel of Citrus pyriformis Hassk. (Rutaceae) resulted in the
      isolation of seven compounds including one coumarin (citropten), two limonoids
      (limonin and deacetylnomilin), and four sterols (stigmasterol, ergosterol,
      sitosteryl-3-beta-D-glucoside, and sitosteryl-6'-O-acyl-3-beta-D-glucoside). From
      the ethyl acetate fraction naringin, hesperidin, and neohesperidin were isolated.
      The dichloromethane extract of the defatted seeds contained three additional
      compounds, nomilin, ichangin, and cholesterol. The isolated compounds were
      identified by MS (EI, CI, and ESI), 1H, 13C, and 2D-NMR spectral data. The
      limonoids were determined qualitatively by LC-ESI/MS resulting in the
      identification of 11 limonoid aglycones. The total methanolic extract of the peel
      and the petroleum ether, dichloromethane, and ethyl acetate fractions were
      screened for their antioxidant and anti-inflammatory activities. The ethyl
      acetate fraction exhibited a significant scavenging activity for DPPH free
      radicals (IC50 = 132.3 microg/mL). The petroleum ether fraction inhibited 5
      lipoxygenase with IC50 = 30.6 microg/mL indicating potential anti-inflammatory
      properties. Limonin has a potent cytotoxic effect against COS7 cells [IC50 =
      (35.0 +/- 6.1) microM] compared with acteoside as a positive control [IC50 =
      (144.5 +/- 10.96) microM].

PMID- 21950164
TI  - Chemical characterization and physical and biological activities of rhamnolipids
      produced by Pseudomonas aeruginosa BN10.
AB  - Pseudomonas aeruginosa BN10 isolated from hydrocarbon-polluted soil was found to
      produce rhamnolipids when cultivated on 2% glycerol, glucose, n-hexadecane, and n
      alkanes. The rhamnolipids were partially purified on silica gel columns and their
      chemical structures elucidated by combination of one- and two-dimensional 1H and
      13C NMR techniques and ESI-MS analysis. Eight structural rhamnolipid homologues
      were identified: Rha-C10-C8, Rha-C10-C10, Rha-C10-C12:1, Rha-C10-C12, Rha2-C10
      C8, Rha2-C10-C10, Rha2-C10-C12:1, and Rha2-C10-C12. The chemical composition of
      the rhamnolipid mixtures produced on different carbon sources did not vary with
      the type of carbon source used. The rhamnolipid mixture produced by Pseudomonas
      aeruginosa BN10 on glycerol reduced the surface tension of pure water from 72 to
      29 mN m(-1) at a critical micellar concentration of 40 mg 1(-1), and the
      interfacial tension was 0.9 mN m(-1). The new surfactant product formed stable
      emulsions with hydrocarbons and showed high antimicrobial activity against Gram
      positive bacteria. The present study shows that the new strain Pseudomonas
      aeruginosa BN10 demonstrates enhanced production of the di-rhamnolipid Rha2-C10
      C10 on all carbon sources used. Due to its excellent surface and good
      antimicrobial activities the rhamnolipid homologue mixture from Pseudomonas
      aeruginosa BN10 can be exploited for use in bioremediation, petroleum and
      pharmaceutical industries.

PMID- 21950165
TI  - Effect of a traditional processing method on the chemical composition of local
      white lupin (Lupinus albus L.) seed in North-Western Ethiopia.
AB  - The effect of a traditional Ethiopian lupin processing method on the chemical
      composition of lupin seed samples was studied. Two sampling districts, namely
      Mecha and Sekela, representing the mid- and high-altitude areas of north-western
      Ethiopia, respectively, were randomly selected. Different types of traditionally
      processed and marketed lupin seed samples (raw, roasted, and finished) were
      collected in six replications from each district. Raw samples are unprocessed,
      and roasted samples are roasted using firewood. Finished samples are those ready
      for human consumption as snack. Thousand seed weight for raw and roasted samples
      within a study district was similar (P > 0.05), but it was lower (P < 0.01) for
      finished samples compared to raw and roasted samples. The crude fibre content of
      finished lupin seed sample from Mecha was lower (P < 0.01) than that of raw and
      roasted samples. However, the different lupin samples from Sekela had similar
      crude fibre content (P > 0.05). The crude protein and crude fat contents of
      finished samples within a study district were higher (P < 0.01) than those of raw
      and roasted samples, respectively. Roasting had no effect on the crude protein
      content of lupin seed samples. The crude ash content of raw and roasted lupin
      samples within a study district was higher (P < 0.01) than that of finished lupin
      samples of the respective study districts. The content of quinolizidine alkaloids
      of finished lupin samples was lower than that of raw and roasted samples. There
      was also an interaction effect between location and lupin sample type. The
      traditional processing method of lupin seeds in Ethiopia has a positive
      contribution improving the crude protein and crude fat content, and lowering the
      alkaloid content of the finished product. The study showed the possibility of
      adopting the traditional processing method to process bitter white lupin for the
      use as protein supplement in livestock feed in Ethiopia, but further work has to
      be done on the processing method and animal evaluation.

PMID- 21950167
TI  - Impact of salicylic acid on the antioxidant enzyme system and hydrogen peroxide
      production in Cucumis sativus under chilling stress.
AB  - Salicylic acid (SA) is a naturally produced compound and has been implicated to
      play important roles in defense of plants against diverse biotic and abiotic
      stresses. To understand how SA functions in the tolerance of cucumber (Cucumis
      sativus) to chilling stress, endogenous SA levels in two different cultivars with
      opposite chilling responsiveness were quantified. Membrane integrity, including
      malondialdehyde (MDA) content and leakage of electrolyte, was also examined in SA
      pretreated cucumber plants under chilling conditions. In addition, activities of
      the two antioxidant enzymes peroxidase (POD) and catalase (CAT) were quantified,
      and hydrogen peroxide (H2O2) production was investigated histochemically in SA
      treated leaves under chilling temperature. Chilling stress resulted in greater
      induction of SA levels in the chilling-tolerant cultivar Changchun mici in both
      leaves and seeds compared to the chilling-sensitive one Beijing jietou, while the
      former one contained higher levels of SA than the latter one in the seeds under
      normal conditions. Pretreatment with SA diminished the increased electrolyte
      leakage and MDA content caused by chilling in the leaves of both cultivars, while
      much less MDA and electrolyte leakage were produced in Changchun mici compared to
      Beijing jietou. Moreover, exogenous application of SA increased significantly the
      POD and CAT activities and soluble protein content. Most importantly, exogenous
      SA treatment could eliminate the accumulation of H202 in leaves and cotyledons of
      both cultivars caused by chilling stress. The data clearly demonstrated that the
      chilling-tolerant cultivar displays a higher SA level than the chilling-sensitive
      one, and that exogenous SA can enhance the chilling tolerance ability, which
      might be achieved through modulating the antioxidant system in cucumber.

PMID- 21950166
TI  - Enantiospecific (S)-(+)-linalool formation from beta-myrcene by linalool
      dehydratase-isomerase.
AB  - The linalool dehydratase-isomerase from Castellaniella defragrans strain 65Phen
      catalyzes in the thermodynamically unfavourable direction the hydration of
      betamyrcene to linalool and further the isomerization to geraniol, the initial
      steps in anaerobic beta-myrcene biodegradation. We have now investigated the
      stereochemistry of this reaction. (S)-(+)-Linalool is formed with an enantiomeric
      excess of at least 95.4%. (R)-(-)-Linalool was not detected. This indicates an
      introduction of the hydroxy group on the si-face of beta-myrcene.

PMID- 21950168
TI  - Methyl jasmonate elicitation enhances glycyrrhizin production in Glycyrrhiza
      inflata hairy roots cultures.
AB  - Hairy roots were induced by infecting stems and leaves of Glycyrrhiza inflata
      with Agrobacterium rhizogenes ATCC 15834. The optimization of growth and
      glycyrrhizin accumulation of G. inflata hairy roots was studied. Sucrose (6%,
      w/v) was optimal for growth and glycyrrhizin accumulation in G. inflata hairy
      roots. Effects of elicitors like chitosan, methyl jasmonate, and yeast extract on
      glycyrrhizin production were studied. Methyl jasmonate (100 microM) was most
      efficient in enhancing glycyrrhizin production up to almost 109 microg/g dry
      weight on day 5 of elicitation. These results indicate that application of
      elicitors can enhance the capacity of G. inflata hairy roots to produce
      glycyrrhizin.

PMID- 21950169
TI  - Isolation of eicosapentaenoic acid-producing fungi from soil based on polymerase
      chain reaction amplification.
AB  - A method was developed for rapid screening and isolation of eicosapentaenoic acid
      (EPA)-producing soil fungi through polymerase chain reaction (PCR) amplification.
      Genes coding for delta6 fatty acid desaturase and delta5 fatty acid desaturase
      were used as molecular markers for screening these EPA-producing fungi from soil.
      Three out of 65 soil fungi gave positive results through PCR amplification. Two
      out of these three strains were found to produce EPA when they had grown in 80 ml
      potato/dextrose liquid medium at (25 +/- 1) degrees C for 144 h. The EPA yields
      were 215.81 mg 1(-1) and 263.80 mg 1(-1), respectively. The other positive strain
      was detected to produce arachidonic acid (AA). This study indicates that
      molecular detection of genes encoding delta6 and delta5 desaturases is an
      efficient method for primary screening of EPA- or its related polyunsaturated
      fatty acids (PuFAs)-producing fungi, which can improve the screening efficiency
      prominently.

PMID- 21950170
TI  - Chemical constituents of the femoral gland secretions of male tegu lizards
      (Tupinambis merianae) (Family teiidae).
AB  - In spite of the importance of chemical signals (pheromones) in the reproductive
      behaviour of lizards, the chemical compounds secreted by their femoral glands,
      which may be used as sexual signals, are only known for a few lizard species.
      Based on mass spectra, obtained by GC-MS, we found 49 lipophilic compounds in
      femoral gland secretions of male tegu lizards (Tupinambis merianae) (fam.
      Teiidae), including a very high proportion of carboxylic acids and their esters
      ranging between n-C8 and n-C20 (mainly octadecanoic and 9,12-octadecadienoic
      acids), with much less proportions of steroids, tocopherol, aldehydes, and
      squalene. We discuss the potential function of these compounds in secretions, and
      compare the compounds found here with those documented for other lizard species.

PMID- 21950171
TI  - The continuing search for safety, permanency, and well-being.

PMID- 21950172
TI  - Factors related to resilience in preschool and kindergarten students.
AB  - This study was designed to examine the relationship between resilience and within
      child characteristics of children under the age of 6. Participants included
      preschool and kindergarten students (N = 29) and their parents and teachers from
      two urban communities in New Jersey. Data were obtained through the Joseph
      Picture Self-Concept Scale (Joseph, 2004), the Devereux Early Childhood
      Assessment (LeBuffe & Naglieri, 1999), and a risk factors survey that was created
      for this study. The authors hypothesized that a significant relationship exists
      among resilience, self-concept, and behavioral concerns. Correlational analyses
      were conducted to determine the extent of each relationship. Results suggest a
      significant negative correlation between resilience and behavioral concerns.

PMID- 21950173
TI  - Addressing substance abuse treatment needs of parents involved with the child
      welfare system.
AB  - The goal of this paper is to synthesize available data to help guide policy and
      programmatic initiatives for families with substance abuse problems who are
      involved with the child welfare system, and identify gaps in the research base
      preventing further refinement of practices in this area. To date, Family
      Treatment Drug Court and newly developed home-based substance abuse treatment
      interventions appear the most effective at improving substance abuse treatment
      initiation and completion in child welfare populations. Research is needed to
      compare the efficacy of these two approaches, and examine cost and child well
      being indicators in addition to substance abuse treatment and child welfare
      outcomes.

PMID- 21950174
TI  - Urban American Indian/Alaskan Natives compared to non-Indians in out-of-home
      care.
AB  - Historically, American Indian/Alaskan Native (AI/AN) children have been
      disproportionately represented in the foster care system. In this study,
      nationally representative child welfare data from October 1999 was used to
      compare urban AI/AN children to non-Indian children placed into out-of-home care.
      Compared to non-Indian children, urban AI/AN children were older, were more often
      male, came from poorer homes, and were more frequently placed into group homes/
      residential placements. Urban AI/AN caregivers had a greater prevalence of
      alcohol abuse and mental health problems compared with non-Indian caregivers.

PMID- 21950175
TI  - Mentoring and social skills training: ensuring better outcomes for youth in
      foster care.
AB  - Youth in foster care face significant life challenges that make it more likely
      that they will face negative outcomes (i.e., school failure, homelessness, and
      incarceration). While the reason(s) for out-of-home placement (i.e., family
      violence, abuse, neglect and/or abandonment) provide some context for negative
      outcomes, such negative outcomes need not be a foregone conclusion. In fact,
      interventions created to serve at-risk youth could ostensibly address the needs
      of youth in foster care as well, given that they often face similar social,
      emotional, and other challenges. Specifically, the author posits that supporting
      foster care youth through the use ofmentoring and social skills training could
      reduce the negative outcomes far too common for many of these youth.

PMID- 21950176
TI  - A culture of education: Enhancing school performance of youth living in
      residential group care in Ontario.
AB  - This article presents a synthesis of what is known about the educational
      experiences of youth living in residential group care based on a literature
      review that highlights both the experiences of the youth themselves and the
      operational context of residential group care in Ontario as it pertains to
      educational performance. The author argues that there is little emphasis on
      education within the residential group care sector in Ontario that could
      translate into more productive educational experiences for youth. The article
      then provides a framework for developing a culture of education for residential
      group care that can be acted upon expeditiously. Enhancing the educational
      performance of young people living in group care will require a cultural approach
      that provides for daily and pervasive education supports and encouragement, and
      aims to enhance the lived experience of young people pursuant to their education.

PMID- 21950177
TI  - Evidence-based practice in group care: the effects of policy, research, and
      organizational practices.
AB  - This article describes the effect of a province-wide vision of evidence-based and
      outcome-based services for children and youth and the challenges of implementing
      evidence-based practice (EBP) and evidence-based treatment (EBT) approaches
      within group care settings. The paper is based on the results of a survey of
      group care settings in the province of Ontario, Canada, which was designed to
      understand the factors affecting the use of EBP and EBT. The critical roles of
      policy, access to research, and organizational structure as they affect the
      frontline workforce were explored. The results identified key differences between
      programs who implemented an evidence-based approach and those who are struggling
      to do so. Differences in case management practices as well as organizational
      factors affect the program's ability to use an evidence-based approach.

PMID- 21950178
TI  - [13-year-old girl. Chronic swelling of both elbows for years].

PMID- 21950179
TI  - [Fox tapeworm is spreading. Avoiding wild berries, caution with pets! (interview
      by Dr. Beate Schumacher)].

PMID- 21950180
TI  - [Anticoagulation in atrial fibrillation. Standard in stroke prevention is
      eliminated].

PMID- 21950181
TI  - [Cardiac primary and secondary prevention. Don't worry, be happy].

PMID- 21950182
TI  - [Oral anticoagulants. Large study finds minor risk of hemorrhage in the elderly].

PMID- 21950183
TI  - [End-of-life decisions: the general practitioner plays a decisive role].

PMID- 21950184
TI  - [End-of-life decisions: current legal situation].

PMID- 21950185
TI  - [End-of-life decisions for patients with dementia and the vegetative state].

PMID- 21950186
TI  - [Treatment decisions for severely ill children and adolescents].

PMID- 21950187
TI  - [Emergency checklist: acute anal fissur].

PMID- 21950188
TI  - [Emergency checklist: mushroom poisoning].

PMID- 21950189
TI  - [Worsening of glucose metabolism, demasquerade of drug induced diabetes
      mellitus].

PMID- 21950190
TI  - [Consensus report. Recommendations for the upcoming influenza vaccination
      season].

PMID- 21950191
TI  - [Surgical management of burns--a matter of correct judgement].

PMID- 21950192
TI  - [Detection of human papillomavirus in gingival fluid of Venezuelan HIV patients
      with periodontal disease].
AB  - Evidence suggests that viruses may be involved in the activation of periodontal
      disease, allowing the overgrowth of periodontal pathogens. The purpose of the
      present study was to detect the presence of Human Papillomavirus (HPV) in
      gingival crevicular fluid (GCF) in HIV+ Venezuelan patients with periodontal
      disease. We evaluated GCF samples from 20 HIV+ patients with periodontal disease
      from the Infectious Disease Center, Faculty of Dentistry, Central University of
      Venezuela, and were clinically examined to establish their periodontal
      conditions, 13 under HAART (antiretroviral therapy) and 7 without HAART. Seven
      seronegative patients with chronic periodontitis and 7 seronegative patients,
      without periodontal disease were included. DNA extraction was performed, the
      consensus primers MY09 and MY11 for the HPV L1 region were used for PCR
      amplification. Genotipification was made for the 6, 11, 16, 18, 31 and 45
      genotypes. HPV were detected in 46% of HIV+ patients under therapy. The CD4 cell
      counts in the IIPV+ patients were not significantly different from the HPV-group.
      The viral load in the HPV+ group was significantly higher (200,470 +/- 324,244
      copy/mL) than in the HPV-patients (10,246 +/- 23,805 copy/mL). Genotypes 6 and 11
      were observed in the HPV positive samples, of which 4/6 (66.6%) presented
      coinfection with both types. No significant differences in the periodontal
      conditions were observed between patients with IIPV-HIV infection related to
      patients with only HIV. HPV was detected only in the gingival crevicular fluid of
      HIV+ patients under HAART independently of the periodontal conditions.

PMID- 21950193
TI  - [Determination of the specificity of seric IgA produced in response to antigens
      of Leishmania (Leishmania) mexicana in murine leishmaniasis].
AB  - In experimental leishmaniasis, the role of antibodies is not entirely clear, as
      some authors consider that these proteins are not involved in protection against
      infection. However, histopathological studies in human and experimental
      leishmaniasis lesions, show plasma cell infiltrates positive for IgA and
      secretion of IgM, IgG and IgA could mediate the formation of immune complexes
      with parasite antigens or self components, favoring necrosis leading to the
      elimination of the parasite. In this study, we determined if the serum IgA in the
      murine model has specific reactivity against antigens of Leishmania (Leishmania)
      mexicana of diagnostic utility. To do this, we used mice either susceptible or
      resistant to cutaneous leishmaniasis, and demonstrated by indirect ELISA that
      serum IgA is elevated in susceptible mice compared with that produced by
      resistant mice. Although other studies in murine models show that the serum IgG
      from mice infected with L. (L) mexicana present cross reactivity with unrelated
      parasite antigens derived from Trypanosoma cruzi, the analysis of the specificity
      of IgA by antigens of L. (L) mexicana and T. cruzi, by Western Blot, showed that
      the IgA serum of mice infected with T. cruzi reacts too with antigens of L. (L)
      mexicana. These findings suggest that IgA may be useful for the clinical
      management and prognosis of the disease.

PMID- 21950194
TI  - [Use of warfarin and low range INR in the prevention of recurrent venous
      thrombosis].
AB  - The object of this work was to determine the efficacy of a low range
      International Normalized Ratio (INR) between 1.5 and 1.9, in preventing recurrent
      venous thrombosis and the hemorrhagic manifestations that can complicate
      anticoagulation with warfarin. Thirty nine patients, 10 to 78 years of age were
      studied between January 2006 and November 2009. All of them had been treated with
      warfarin, for at least 6 months, due to deep venous thrombosis or pulmonary
      embolism. The subjects were separated, at random, into two groups. In group A (20
      patients), the doses of warfarin were adjusted until the INR was stabilized
      between 1.5 and 1.9; in group B, the INR was maintained between 2 and 3. The
      coagulant activities of plasma factors II, VII, IX and X were determined in a
      week and between the fourth and fifth weeks, after stabilization of the INR.
      Plasma activities of the coagulation factors assayed were abnormally low in both
      groups, in the two opportunities they were determined, although significantly
      lower in group B (p<0.05). No thromboembolic episodes occurred during the study,
      in any of the patients. One of the patients from group A and four from group B,
      presented minor hemorrhagic manifestations (p N.S.) The above results suggest
      that a range on INR lower that 2, could be sufficient to prevent recurrent
      thrombotic episodes while diminishing the frequency of hemorrhagic complications
      associated with the use of warfarin. However, it is necessary to continue
      incorporating more individuals in the study to obtain greater certainty in the
      analysis of these results.

PMID- 21950195
TI  - [Oxidative stress in soleus and extensor digitorum longus (EDL) muscles of
      spontaneously hypertensive rats].
AB  - Systemic diseases affect skeletal muscle, and inflammation and oxidative stress
      are some of the involved mechanisms. There is scarce information about the
      effects of essential hypertension on skeletal muscle. The soleus and extensor
      digitorum longus (EDL) muscles of spontaneously hypertensive rats (SHR) were
      studied compared to control Wistar Kyoto (WKY) rats. The levels of nitrite and
      nitrate in micromol/mg-protein; endothelial (eNOS), neuronal (nNOS), and
      inducible (iNOS) nitric oxide synthases, nitrotyrosine and tumour necrosis factor
      alpha (TNF-alpha) in ng/mg-protein were determined. Compared with controls, the
      SHR showed increased levels of nitrotyrosine (soleus 24.4 +/- 5.0 vs. 3.3 +/-
      0.3, p<0.001; EDL 20.2 +/- 4.3 vs. 4.5 +/- 0.4, p<0.0037), iNOS (soleus 26.6 +/-
      3.7 vs. 8.3 +/- 0.9; EDL 21.3 +/- 3.7 vs. 11.0 +/- 0.8, both p<0.0001) and TNF
      alpha (soleus 2.2 +/- 0.5 vs. 0.6 +/- 0.1, p<0.05; EDL 1.9 +/- 0.2 vs. 0.6 +/-
      0.1, p<0.02). A decrease of eNOS was found in soleus muscle (20.6 +/- 1.4 vs.
      30.3 +/- 1.2, p<0.00001); of nNOS (soleus 16.8 +/- 1.4 vs. 20.7 +/- 1.8, p< 0.05;
      EDL 13.6 +/- 1.3 vs. 21.9 +/- 1.8, p<.005) and nitrite in EDL (5.8 +/- 0.3 vs.
      7.1 +/- 0.5, p<0.026).There was a positive correlation between TNF-alpha vs.
      nitrotyrosine in soleus (r=0.798; p<0.031) and a tendency in EDL (r=0.739;
      p=0.059); iNOS vs. nitrotyrosine (soleus: r=0.908; p<0.0001; EDL: r=0.707;
      p<0.01), a tendency between TNF-alpha and iNOS (EDL: r=0.736; p<0.059); and a
      negative correlation between eNOS vs. nitrotyrosine in soleus muscle (r=-0.816;
      p<0.0012). In conclusion, in skeletal muscles of SHR an inflammatory process was
      found evidenced by the increase in TNF-alpha, nitrotyrosine and iNOS. The
      decreased levels of constitutive synthases, together with the higher level of
      iNOS, are indicative of endothelial dysfunction.

PMID- 21950196
TI  - Effectiveness of melatonin in tardive dyskinesia.
AB  - Tardive Dyskinesia (TD) is a movement disorder associated with the clinical
      administration of antipsychotics. It is believed that TD is due, among other
      factors, to an increase in the oxidative damage produced by free radicals.
      Antioxidants, like vitamin E, have been used in the treatment of TD but there is
      no evidence of their effectiveness. Melatonin (MEL) is 6 to 10 times more
      effective, as an antioxidant, than vitamin E and it has been used with an
      apparent higher effectiveness in the treatment of TD, although the results have
      not been conclusive. A randomized, double blind, placebo controlled design was
      used to determine the effectiveness of MEL (20 mg/day) during 12 weeks in 7
      patients with TD. Six patients with TD were treated with placebo. The Abnormal
      Involuntary Movement Scale (AIMS) was chosen to assess the severity of TD
      initially and after 4, 8 and 12 weeks. The psychiatric evaluation was done
      following the Brief Psychiatric Rating Scale. In two patients treated with MEL a
      significant improvement (more than 60%) of the values of AIMS was detected. In
      the remainder five, as well as in the patients treated with placebo, no
      difference was observed during the 12 weeks. When compared the AIMS score in all
      the MEL-treated patients with the values in the placebo-treated patients, no
      significant differences were detected during the 12 weeks of the study. However,
      the significant clinical improvement observed in two patients must be considered
      before reaching a final conclusion on the usefulness of MEL in TD.

PMID- 21950197
TI  - [Pearson syndrome. Case report].
AB  - Among the etiologies of anemia in the infancy, the mitochondrial cytopathies are
      infrequent. Pearson syndrome is diagnosed principally during the initial stages
      of life and it is characterized by refractory sideroblastic anemia with
      vacuolization of marrow progenitor cells, exocrine pancreatic dysfunction and
      variable neurologic, hepatic, renal and endocrine failures. We report the case of
      a 14 month-old girl evaluated by a multicentric study, with clinic and molecular
      diagnosis of Pearson syndrome, with the 4,977-base pair common deletion of
      mitochondrial DNA. This entity has been associated to diverse phenotypes within
      the broad clinical spectrum of mitochondrial disease.

PMID- 21950198
TI  - Melanosis of the vagina and human papillomavirus infection, an uncommon
      pathology: case report.
AB  - Benign melanotic lesions of the vagina are uncommon and only a few cases have
      been reported in the literature. A 34-year-old woman was referred because of a
      Vaginal Intraepithelial Neoplasia 1 biopsy result. On the gynecological
      examination, two different hyperpigmented areas were noted in the vagina. The
      colposcopic visualization of the cervix and vagina found an aceto-white lesion at
      the right lateral wall of the upper third of the vagina. Biopsies from three
      areas were taken. Histological study reported a melanosis of the vagina and HPV
      infection. An immunohistochemical panel of epithelial markers was performed in
      vaginal samples, such as Cytokeratin AE1/AE3 and epithelial membrane antigen,
      mesenchymal marker: vimentin; melanocytic makers: protein S-100 and HMB45 (Human
      Melanoma Black); proliferating cell marker: proliferating cell nuclear antigen
      (PCNA), and P-53 oncoprotein. High Risk (16, 18, 31, 45) and Low Risk (6, 11) HPV
      types were studied by In Situ Hybridization using the same vaginal samples. CK,
      EMA and Vimentin were 2+. Melanocytic markers, HMB45 and S100, and PCNA were 1+
      in basal cell layer. P-53 was negative. The melanotic tissue and acetowhite
      lesion were positives to HPV Types 6,11. In conclusion, melanosis of the vagina
      is a uncommon benign pathology. Usually, melanosis is present in women over 40
      years old. We present a case of melanosis of the vagina in a young woman infected
      with low-risk HPV types and review the literature.

PMID- 21950199
TI  - [Relevance of apoptosis in the female reproductive system].
AB  - Apoptosis is a genetically controlled form of cell suicide. Due to the cyclic
      nature of the female reproductive system, the ovary, the endometrium and the
      mammary gland sustain continuous cycles of cell growth and apoptosis in response
      to hormonal changes. Apoptotic cell death plays multiple roles during embryonic
      and organ development. It is involved in sculpturing tissues and serves to delete
      structures that are no longer required. It is clear that apoptosis plays an
      active and important role in ovarian physiological functions. Apoptosis plays a
      major role during folliculogenesis and dominant follicle selection and also plays
      part in corpus luteum regression. In addition, it has been shown that programmed
      cell death plays important roles in the mammary gland development and ductal
      morphogenesis. During puberty, lumen formation is associated with the selective
      apoptosis of centrally located cells. In turn, postlactational involution of the
      mammary gland is characterized by the secretory epithelial cells undergoing
      programmed cell death. Apoptosis has also been associated with physiological, as
      well as pathological, endometrial processes such as cancer and endometriosis. The
      delicate balance between apoptosis and cell proliferation is essential in
      controlling the cyclical growth of the reproductive tissues and plays an
      important role in the prevention of neoplastic transformation.

PMID- 21950200
TI  - Molecular characterisation of the quinolone resistance-determining region (QRDR)
      of the parC gene locus in viridans-group streptococci.
AB  - Forty-eight isolates of viridans-group streptococci (VGS) from adults and
      children in the community are examined for their resistance to ciprofloxacin
      phenotypically by determination of the minimum inhibitory concentration (MIC). In
      addition, the parC gene locus is amplified and sequenced in all isolates and
      mutations noted. Overall, 44 VGS organisms were found to be susceptible to
      ciprofloxacin by the broth microdilution method, and the remaining four strains
      had intermediate susceptibility. Reduced MICs were observed with intermediate
      strains when reserpine was added to the broth, inhibiting any efflux activity.
      Overall, the effect of adding reserpine to the broth medium was to add one
      doubling dilution to the MIC in the case of Streptococcus mitis, S. oralis and S.
      salivarius, as well as to increase the MIC by two doubling dilutions in two of
      the three S. parasanguinis isolates. Amino acid sequence analysis of the
      quinolone resistance-determining region (QRDR) of the parC gene locus showed good
      correlation to the phenotypic resistance to ciprofloxacin, where no confirmed
      mutation conferring quinolone resistance was found. Eleven amino acid positions
      showed discordance with S. pneumoniae R6 and eight (S52, F55, S58, N91, E135,
      K137, F141 and S167) were common in the VGS species examined. In addition, minor
      substitutions were found at three positions (D51, T54 and V86). In conclusion,
      this study demonstrates the low occurrence of ciprofloxacin resistance in a
      population of VGS isolated from the community. In addition, several silent
      mutations were noted in VGS organisms without any increase in MIC against
      ciprofloxacin.

PMID- 21950201
TI  - Creatinine level as a predictor of hypertensive disorders during pregnancy.
AB  - This study aims to examine the association between creatinine level during the
      first 20 weeks of pregnancy and the development of pre-eclampsia in the second
      half of the pregnancy. The study population included all registered births
      (n=9341) between 2001 and 2007 in a tertiary medical centre. Student's t-test and
      receiver operating characteristic (ROC) curves were used to determine any
      association. Significant association was documented between creatinine level in
      the first 20 weeks and the prevalence of hypertensive disorders. The mean plasma
      creatinine value in women with mild pre-eclampsia versus healthy women was 0.59
      mg/dL +/- 0.14 versus 0.57 mg/dL +/- 0.15, respectively (P = 0.023). The mean
      plasma creatinine value in women with severe pre-eclampsia versus healthy women
      was 0.61 mg/dL +/- 0.17 versus 0.58 mg/dL +/- 0.15, respectively (P = 0.040). The
      mean plasma creatinine value in women with hypertensive disorders versus healthy
      women was 0.60 mg/dL +/- 0.15 versus 0.58 mg/dL +/- 0.15, respectively (P=0.003).
      The ROC curve demonstrated a significant association between creatinine level in
      the first 20 weeks of pregnancy and the development of mild and severe pre
      eclampsia in the second half of pregnancy (area under the curve: 0.54, 95%
      confidence interval [CI]: 0.51-0.57, P = 0.02, and 0.56, 95% CI: 0.50-0.62, P =
      0.033, respectively). Higher creatinine levels during the first 20 weeks of
      pregnancy are associated with a higher risk of developing mild and severe pre
      eclampsia.

PMID- 21950202
TI  - Validation of a norovirus multiplex real-time RT-PCR assay for the detection of
      norovirus GI and GII from faeces samples.
AB  - Norovirus is a leading cause of infectious non-bacterial gastroenteritis. The
      virus is highly contagious and has multiple modes of transmission, presenting a
      growing challenge to hospital-based healthcare. In this study, a total of 120
      stool samples are tested for the presence of norovirus GI and GII by the Roche
      two-step Lightcycler 2.0 assay incorporating primers and probes produced by TIB
      Molbiol, and the results are compared with results from the National Virus
      Reference Laboratory. The Roche/TIB Molbiol assay produced 51 positive results
      and 69 negative results. Discrepancy analysis was performed for six conflicting
      results using a second real-time polymerase chain reaction (PCR) assay (Roche/TIB
      Molbiol) and this confirmed that four of the five discrepant positive results
      were true positives. A single discrepant negative result generated by the Roche
      assay remained negative using the second assay. Sensitivity, specificity,
      positive predictive value (PPV) and negative predictive value (NPV) were
      calculated to be 98%, 98.6%, 98.0% and 98.6%, respectively. Melting curve
      analysis was used to differentiate genogroups I and II and this showed that 92%
      of strains belonged to genogroup II.

PMID- 21950203
TI  - Serum globulins contribute to the discrepancies observed between the bromocresol
      green and bromocresol purple assays of serum albumin concentration.
AB  - The bromocresol green (BCG) and bromocresol purple (BCP) assays often yield
      discordant serum albumin results. This study seeks to test the hypothesis that
      bias in albumin results are influenced by the concentration of serum globulin
      subtypes. The concentrations of serum albumin, alpha1-globulin, alpha2-globulin,
      beta-globulin and gamma-globulin are determined in 197 human serum specimens by
      total serum protein quantification and protein electrophoresis, and by the BCG
      and BCP assays. The influence of globulins on albumin measurement is validated
      with protein mixtures of albumin and globulins. The BCG assay bias was directly
      proportional to the concentrations of alpha1-globulin and alpha2-globulin, and
      inversely correlated with the concentrations of beta-globulin and y-globulin (r2
      = 0.793). The BCP assay bias was inversely proportional to the concentration of
      al-globulin and alpha2-globulin (r2 = 0.464) but not related to the
      concentrations of beta-globulin or y-globulin. Among the 197 study participants,
      those with nephrotic syndrome had a significantly higher level of alpha2-globulin
      compared to those in other categories. Thus, the authors conclude that serum
      globulins contribute to the bias seen in the BCG and BCP assays, with the
      greatest effects observed for a-globulin on the BCG assay where higher
      concentrations contributed to a higher bias.

PMID- 21950204
TI  - A cost-effective protocol for screening patients for methicillin-resistant
      Staphylococcus aureus.
AB  - The incidence of hospital-acquired infection with methicillin-resistant
      Staphylococcus aureus (MRSA) is rising worldwide. Rapid identification of MRSA
      carriers is an important step in reducing the risk of transmission to other
      patients. Molecular methods are increasingly popular but are technically
      demanding and expensive. This study assesses the modification of one of the
      commercially available latex agglutination tests (Mastalex-MRSA) for the
      identification of penicillin-binding protein 2' on known strains of MRSA as well
      as other organisms identified from chromogenic agar plates. A total of 3050
      patients with unknown MRSA status were processed through the routine laboratory
      during the investigation period and 73 of these were presumptive positive
      following overnight incubation. Of 70 patients who could be evaluated, 32 (43.8%)
      specimens would be suitable for use with the kit directly from overnight
      incubation on chromogenic agar, and the other 38 (52.1%) would be suitable
      following four hours' incubation on blood agar. The cost of one positive MRSA
      test with the inclusion of this test is Euro 15.15 compared with published
      reports of Euro 35.00 for a commercial polymerase chain reaction (PCR) test. This
      protocol would allow the reporting of presumptive positive MRSA results
      approximately 24 hours earlier than currently achieved.

PMID- 21950205
TI  - Thymoquinone, the active ingredient of Nigella sativa seeds, enhances survival
      and activity of antigen-specific CD8-positive T cells in vitro.
AB  - Recent preclinical and clinical studies provide evidence that adoptive transfer
      of in vitro activated T cells can results in significant antitumour responses in
      vivo upon acquisition of certain survival and homing properties during in vitro
      activation. Based on recent studies showing in vivo antioxidant effects of
      thymoquinone (TQ), the active ingredient of Nigella sativa seeds, this study aims
      to determine whether or not TQ can increase survival and sustain the expression
      of the homing receptor CD62L in antigen-specific T cells in vitro. The results
      showed that stimulation of OT-1 (transgenic CD+) T cells with OVA antigen
      resulted in activation, as shown by a decrease in the surface expression of CD62L
      which coincided with significant apoptosis measured three and five days after
      antigen stimulation. Addition of low concentrations of TQ during CD85+ T-cell
      activation resulted in enhanced survival of the activated T cells and sustained
      expression of CD62L. These effects coincided with enhancement in the capability
      of CD8+ T cells to produce the effector cytokine interferon-gamma (IFNgamma).
      These results suggest that TQ has a beneficial effect in conditioning T cells in
      vitro for adoptive T-cell therapy against cancer and infectious disease.

PMID- 21950206
TI  - Variation in CAG and GGN repeat lengths and CAG/GGN haplotype in androgen
      receptor gene polymorphism and prostate carcinoma in Nigerians.
AB  - Prostate cancer has become the most common cancer in Nigerian men. The growth of
      the prostate gland depends on circulating androgens and intracellular steroid
      signalling pathways. The effects of androgens are mediated through the androgen
      receptor (AR), a nuclear transcription factor encoded by the AR gene. The common
      polymorphisms, CAG and GGN repeats, in exon 1 of this gene have been implicated
      as possible risk factors. Thus far, existing supporting data are scanty and none
      are from sub-Saharan African populations. Therefore, this study investigates the
      possible association between AR polymorphism repeat length (CAG and GGN) and
      prostate cancer in Nigerians. A total of 261 subjects (70 with prostate cancer,
      68 with benign prostate hyperplasia [BPH], 123 age-matched apparently normal
      subjects as controls) were studied. CAG and GGN repeats length were determined by
      fragment length analysis using GeneScan. The CAG repeat length in prostate cancer
      and in BPH compared to the controls was significantly different (P < 0.05) with
      reduce length of CAG repeats showing a significant odds ratio (OR) in both cases.
      However, this was not observed in GGN repeat length, which showed no significant
      difference between cases and controls (P > 0.05). CAG and GGN haplotype variation
      showed no significant difference between cases and controls (P > 0.05), except
      that the haplotypes CAG > or =21 and GGN < or =21 were more common in the control
      group. The results of this study, the first from sub-Saharan Africa, supports the
      hypothesis that reduced CAG repeat length is a risk factor for prostate cancer,
      and also suggests an association with BPH.

PMID- 21950208
TI  - Stability of 27 biochemistry analytes in storage at a range of temperatures after
      centrifugation.
AB  - Knowledge of factors affecting sample integrity is vital to make informed
      judgements on the validity of results. However, the information available for
      sample stability is incomplete, confusing and conflicting, particularly post
      centrifugation. This study aims to investigate the effects of storage conditions
      on biochemical analytes. As part of this study, a new method has been developed,
      based on the manufacturer's stated analytical precision for the methodology. Ten
      adult volunteers were recruited into the study. Blood was collected into serum
      separating tubes, and allowed to clot at room temperature for 30 minutes. After
      centrifugation, serum samples were stored frozen, refrigerated or at ambient
      temperature for between two hours and three months. After the allotted time had
      elapsed, designated serum aliquots were stored at -80 degrees C, before batch
      analysis for 27 biochemical analytes. Twenty-three out of the 27 analytes
      remained stable until the last time-point tested at all temperature conditions.
      Alanine aminotransferase (ALT), lactate dehydrogenase (LD-P), potassium and uric
      acid showed reduced stability with at least one of the storage conditions tested.
      The method developed provided robust sample stability data within the inherent
      imprecision of the assay(s) used. The results generated can be used to create an
      evidence-based policy recommending sample handling and transportation practices
      that will ensure optimal sample integrity, and permit informed judgements to be
      made on results of stored samples. Minimal effects on sample stability were noted
      for the majority of analytes using the storage conditions tested in this study.

PMID- 21950207
TI  - Prevalence of hepatitis B genotype and viral basic core promoter and precore
      mutations among teenagers in Macao: relationship with hepatocellular carcinoma
      development.
AB  - Chronic hepatitis B virus (HBV) infection is a global problem and over 75% of
      cases are reported in the Asia Pacific region. Infection can lead to progressive
      liver disease, cirrhosis and hepatocellular carcinoma (HCC). Previous studies
      suggest the prevalence of HBV carriers in Macau to be approximately 10% of the
      population. This study aims to investigate the prevalence of HBV genotypes among
      HBV-positive teenagers in Macao and the prevalence of base core promoter (BCP)
      and precore (PreC) mutations in the viral genome. In addition, through monitoring
      aminotransferase and alpha-fetoprotein, it aims to investigate relationships
      among HBV genotypes, BCP/PreC mutations and HCC development. This study recruited
      1991 teenagers in Macau in 2008, and the PreS1/S2, BCP and PreC region of the HBV
      genome from 34 HBsAg-positive subjects were amplified and sequenced to determine
      HBV genotype and presence of HCC-associated mutations. Results suggested that the
      average rate of HBV infection among secondary school teenagers in Macao is low,
      and HBV genotype B and C viruses were found to predominate in Macao. The BCP/PreC
      mutations A1762T, G1764A, G1896A and C1766T were identified in 2.9-11.7% of
      subjects. However, no significant relationship was observed between HBV genotype,
      BCP/PreC mutations and HCC development.

PMID- 21950209
TI  - Predicting tumour response to anti-HER1 therapy using medical imaging: a
      literature review and in vitro study of [18F]-FDG incorporation by breast cancer
      cells responding to cetuximab.
AB  - Cetuximab, an anti-HER1 (EGFR) antibody, is currently under trial for the
      treatment of breast cancer. HER1 expression is not necessarily a predictor of
      response to cetuximab as mutant components of the pathways activated by HER1
      which include PI3K/Akt can lead to resistance. Techniques that monitor events
      downstream of HER1 are more likely to provide an accurate measure of the efficacy
      of an anti-HER1 treatment. Glucose metabolism has been shown to be strongly
      influenced by the state of activation of PI3K/Akt. Here, the association between
      [18F]-FDG incorporation in breast cancer cells during response to cetuximab is
      investigated. The study also reviews the development of medical imaging probes
      that target HER1 The sensitivity to cetuximab of three breast tumour cell lines,
      SKBr3, MDA-MB-453 and MDA-MB-468, expressing HER1 at low and high levels, are
      determined using an MTT assay over a six-day period and a clonogenic assay
      carried out after seven- and 10-day exposures. Incorporation of FDG by cells
      treated with growth inhibitory doses of cetuximab were carried out after 4 hand
      two, four and six days of treatment. Glucose transport (rate of uptake of the non
      metabolisable analogue [3H]o-methyl-D-glucose), hexokinase activity and lactate
      production were measured on cells treated with inhibitory doses of cetuximab for
      six days. The IC50, dose for MDA-MB-468 cells and the IC10 (maximum achievable
      inhibition) doses for MDA-MB-543 and SKBr3 treated with cetuximab for six days
      were 2.6, 5 and 148 microg/mL, respectively. Incorporation of FDG by SKBr3 and
      MDA-MB-453 cells was found to be decreased by MDA-MB468 cells using IC50, and
      IC20, doses of cetuximab for six days. Lactate production was found to be
      increased by MDA-MB-468 cells responding to cetuximab. Incorporation of FDG at
      the tumour cell level is modulated by treatment with growth inhibitory doses of
      cetuximab in cells sensitive to cetuximab due to modulation of HK activity.

PMID- 21950210
TI  - Deaths: leading causes for 2007.
AB  - OBJECTIVES: This report presents final 2007 data on the 10 leading causes of
      death in the United States by age, race, sex, and Hispanic origin. Leading causes
      of infant, neonatal, and postneonatal death are also presented. This report
      supplements the Division of Vital Statistics' annual report of final mortality
      statistics. METHODS: Data in this report are based on information from all death
      certificates filed in the 50 states and the District of Columbia in 2007. Causes
      of death classified by the International Classification of Diseases, Tenth
      Revision (ICD-10) are ranked according to the number of deaths assigned to
      rankable causes. Cause-of-death statistics are based on the underlying cause of
      death. RESULTS: In 2007, the 10 leading causes of death were, in rank order:
      Diseases of heart; Malignant neoplasms; Cerebrovascular diseases; Chronic lower
      respiratory diseases; Accidents (unintentional injuries); Alzheimer's disease;
      Diabetes mellitus; Influenza and pneumonia; Nephritis, nephrotic syndrome and
      nephrosis; and Septicemia. They accounted for approximately 76 percent of all
      deaths occurring in the United States. Differences in the rankings are evident by
      age, sex, race, and Hispanic origin. Leading causes of infant death for 2007
      were, in rank order: Congenital malformations, deformations and chromosomal
      abnormalities; Disorders related to short gestation and low birth weight, not
      elsewhere classified; Sudden infant death syndrome; Newborn affected by maternal
      complications of pregnancy; Accidents (unintentional injuries); Newborn affected
      by complications of placenta, cord and membranes; Bacterial sepsis of newborn;
      Respiratory distress of newborn; Diseases of the circulatory system; and Neonatal
      hemorrhage. Important variations in the leading causes of infant death are noted
      for the neonatal and postneonatal periods.

PMID- 21950211
TI  - [Leptospire infections in pigs: epidemiology, diagnostics and worldwide
      occurrence].
AB  - Leptospirosis is a systemic disease affecting humans and animals, and pigs are
      generally considered the reservoir host species for the serovars Pomona,
      Bratislava and Tarrasovi. Endemic infections in swine herds generally remain
      subclinical, as do the vast majority of leptospire infections. However, when a
      susceptible breeding herd is infected for the first time or its immunity is
      compromised, considerable losses can occur due to abortion, stillbirths, weakly
      piglets or infertility. Infections in pigs caused by other serovars tend to occur
      only incidentally, vary regionally, and depend on other reservoir hosts,
      primarily rodents. Leptospires persist in porcine kidneys, and the Bratislava
      serovar, in the genital tract; it is excreted in urine and genital fluids.
      Leptospirosis is transmitted by direct or indirect contact with an infected
      animal. Fundamental research on porcine leptospirosis was conducted in the 1970s
      and 1980s. However, despite subsequent application of the most recent molecular
      biological methods, the pathogenesis of porcine leptospirosis is still largely
      unknown, and research results from the last 25 years on its incidence are very
      heterogeneous, due not only to regional differences but also to differences in
      the evaluation of diagnostic and population studies. Serological testing of pigs
      showed serovar prevalences ranging between as much as 16.3% (Pomona) and
      generally no more than 2.9% (Tarassovi), whereas antibodies against Bratislava
      were found in as many as 41.8% of pigs tested during the last 20 years, as in
      previous studies, indicating that this remains the most prevalent serovar.

PMID- 21950212
TI  - [Identification of Mycobacterium avium ssp. paratuberculosis infected dairy herds
      by environmental sampling].
AB  - In herds with known prevalence (P) use of environmental sampling (ES) to detect
      Mycobacterium avium ssp. paratuberculosis (MAP) infected cattle herds was proofed
      in relation to P. In 31 MAP-infected free stall dairy herds and 15 non-infected
      herds P was defined by annually repeated whole herd testing by fecal culture (34
      877 individual samples). Eight infected herds had a very low (> 0-2%), 14 a low
      (> 2-5%), four a medium (> 5-10%), and five a high P (> 10%). A mean number of
      nine environmental samples per herd were collected from the floor of lactating
      cows, milking, calving and sick cow areas and the crossover to the calf area.
      After twelve weeks cultivation on HEYM-medium with and without mycobactin
      positive samples were further characterized by PCR. All non-infected herds (100%)
      showed negative and 22 (71%) of the infected herds positive results in ES. Nine
      infected herds with negative ES results had a low P (0.04-4,04%). Proportion of
      positive ES depended on P and on sampling areas with 53.3% positive results in
      lactating cow areas and 45.2% in milking areas. For P > 5%, ES in these two areas
      caused a positive herd status; herds with P < 5% required sampling in the other
      areas too. The ES method has a herd sensitivity of 87% for dairy herds with P >
      2% and provides an efficient tool to determine MAP infection status or herd
      prevalence.

PMID- 21950213
TI  - Evaluation of carbon dioxide anaesthesia for the castration of male suckling
      piglets by stress hormone concentrations, behaviour and clinical factors.
AB  - The objective of this study was to examine the effect of an anaesthesia using 70%
      carbon dioxide and 30% oxygen on endocrine stress reaction, behaviour and
      clinical parameters of male suckling piglets during castration. One hundred and
      seventy one male piglets, three to five days of age, were allocated to two
      experiments. They were assigned either to the procedures control handling,
      control castration, handling under anaesthesia or castration under anaesthesia in
      each experiment. In Experiment 1, adrenaline and noradrenaline plasma
      concentrations were measured in blood samples taken before (-15 min) and after
      (immediately, 2 min) handling/castration. In Experiment 2, behavioural
      observations and clinical parameters such as heart and respiratory rate, oxygen
      saturation, reflexes and recovery time were assessed at several sampling times.
      Measurement of adrenaline and noradrenaline concentrations revealed an increase
      in all groups after handling/castration (p < 0.0167), but higher concentrations
      were seen in the anaesthetized groups (25 to 93 times) than in control groups
      (two to four times). The excessive endocrine reaction suggests that carbon
      dioxide inhalation causes a more stressful situation in piglets compared to
      castration without anaesthesia. Behavioural abnormalities, significant decreases
      in the heart rate, the respiratory rate and the oxygen saturation (p < or =
      0.001) including a cardiac arrhythmia (extrasystoles) underline the impression
      that CO2 inhalation anaesthesia negatively affects animal welfare. Based on the
      results of this study, this anaesthetic method is unsuitable to reduce stress
      induced by castration. Further research on alternatives is necessary to ensure
      the well-being of the piglets during castration.

PMID- 21950214
TI  - [Notification for intended animal research - remarks on the future procedures on
      the basis of the European Union Laboratory Animal Guideline 2010/63/EU].
AB  - The new Directive 2010/63/EU on the protection of animals used for scientific
      purposes causes a need of several changes in German animal welfare law. On the
      basis of the regulations in the Directive, adjustments of the existing
      notification procedures are unavoidable. The Directive includes provisions for a
      simplified administrative procedure which differs significantly from the existing
      notification procedures. In any case, an application process will be required for
      projects in the meaning of the Directive. This contribution comments on the
      conceivable changes of the existing notification procedure. The implementation of
      the provisions of the Directive into national law has to be done near-term as the
      Directive is applicable from January 1st 2013. In advance, political and legal
      procedures must be passed through, the adapted regulations are to be notified by
      the European Commission and last but not least the authorities and user
      establishments must have enough time to implement the necessary changes.

PMID- 21950215
TI  - Controlled but pragmatic investigations of interventions for behavioural
      disturbances in dogs and cats.
AB  - Veterinarians are often directly involved in clinical studies or requested for
      information to help interpret their results. Therefore, it is reasonable to
      examine the reservoir of study methods. This article transfers methodological
      considerations from clinical research into veterinary medicine. The study
      question determines the appropriate study method. Recently a ten-step procedure
      was suggested for selection of appropriate study designs in humans. Based on this
      approach, a pragmatic study design was adapted to the conditions prevailing in
      interventional studies in dogs and cats with disturbed behaviour. The different
      concepts for clinical studies are introduced. Whether or not the design and the
      evaluation of pragmatic studies in dogs and cats with disturbed behaviour has
      been maintained and the prerequisites have thereby been fulfilled so that the
      obtained results are suitable to be applied under everyday conditions can be
      tested in eight steps. Using the pragmatic design the superiority of complex
      interventions can be investigated. The results of pragmatic studies help to
      substantiate a value judgement, i. e., the recommendation or rejection of a
      specific therapeutic intervention for a defined disease entity in a specific
      therapeutic setting. The goal of pragmatic studies is to obtain results
      appropriate for use in everyday situations. In conclusion, the suggested
      procedure is useful for the selection of the appropriate study designs for
      specific questions. This procedure is also suitable to test whether the
      conclusions of published study results coincide with the chosen methods.

PMID- 21950216
TI  - Clinicopathologic diagnosis of cutaneous toxoplasmosis in an Angora cat.
AB  - This report deals with a case of cutaneous toxoplasmosis in a 2 year-old female
      Angora cat. Cutaneous lesions were characterized by prescapular ulcers and
      hyperemic nodules in the skin of the inguinal and dorsosacral regions. A skin
      biopsy sample was collected from the lesioned area and processed for
      histopathologic examination and immunoperoxidase test using Toxoplasma gondii and
      Neospora caninum specific antibodies. Toxoplasma gondii immunopositive reactions
      were detected in keratinocytes and dermal macrophages while no immunoreactivity
      was detected for N. caninum. The case of cutaneous toxoplasmosis was further
      confirmed by PCR analysis using T. gondii B1 gene-specific primers. In
      conclusion, we report the first case of cutaneous toxoplasmosis in Angora cats.

PMID- 21950217
TI  - [Reproducibility of bovine neonatal pancytopenia (BNP) via the application of
      colostrum].
AB  - A haemorrhagic diathesis has been observed in young calves since 2007 which is
      described as bovine neonatal pancytopenia (BNP) and presents a completely new
      disease. The objectives of our investigation were to test if BNP could be
      reproduced using colostrum of cows with a BNP history and pre-colostral calves
      from farms where BNP has not been observed. In the present experiment, 22 German
      Holstein calves from BNP-free farms were fed four to six hours after birth 2.5 l
      colostrum from cows which had been reported to have had at least one calf with
      BNP in the last lactation. We distinguished three different experimental groups
      according to the composition of the colostrum. In experimental group I, each of
      the six calves received colostrum of a single cow, in experimental group II all
      six calves received colostrum from the same cow and in experimental group III
      each of the ten calves received a colostrum mix from ten different cows. Clinical
      signs of BNP were observed in 50% of the calves in experimental group I, 67% of
      the calves in experimental group II and all calves in experimental group III. The
      lethality in the three experimental groups was significantly different with rates
      of 16.7%, 66.7% and 80%, respectively. Calves fed with a colostrum-mix in
      experimental group III had the highest lethality. Neither the farm nor the amount
      of the colostrum fed had a significant effect on the occurrence and course of
      BNP. The profiles for thrombocytes, leucocytes and erythrocytes significantly
      differed in dependence of the severity of BNP signs. Calves with non-lethal BNP
      showed thrombocytopenia with values below 100 G/l on the 1th to 3rd and the 7th
      to 11th day of life. In calves with lethal BNP, thrombocytes decreased under 50
      G/l from day 5. In calves with non-lethal BNP, a decrease of the leucocytes under
      the threshold was present only for a short period of time. In calves with lethal
      BNP, leucocytes decreased in the first 5 days after birth continuously and
      increased on the 6th to the 8th day to normal values and then a rapid decrease
      occurred. Erythrocytes decreased under the normal threshold just in the last two
      days before the calves died or were euthanized. Thus, the present experiments
      showed that colostrum of cows with a BNP-history and vaccination with PregSure
      BVD from Pfizer caused lethal BNP. We can assume that the different reactions of
      the calves are due to immunogenetic reactions to colostral alloreactive
      antibodies. The reaction spectrum of calves depends on the presence of antigens
      which can react with these colostral antibodies. The experimental results can
      explain the different incidences of BNP within and among farms as well as between
      breeds.

PMID- 21950218
TI  - [Report on Salmonella isolates submitted to the German National Reference
      Laboratory for running analyses and tests on zoonoses (Salmonella) in the year
      2009].
AB  - The present report deals with Salmonella strains received at the German National
      Reference Laboratory for Salmonella (NRL-Salm) for routine diagnostic in the year
      2009. Hence, the working group continues the previous report from Friedrich et
      al. (2010) about the documentation on the serovar distribution of Salmonella
      received at the NRL-Salm in the years 2004-2008. As in the recent years, most of
      the Salmonella strains originated from livestock and food. In the year 2009 the
      NRL-Salm received 4765 isolates, most of them (85,1 %) were routine diagnostic.
      Salmonella ser. Typhimurium, its monophasic variant S. enterica subspecies
      enterica serovar 1,4,[5],12:i:- and Salmonella ser. Enteritidis were the most
      prevalent serovars. The number of S. enterica subsp. enterica serovar
      1,4,[5],12:i:- isolates increased in 2009, in comparison to the years 2004-2008,
      and became the second most prevalent serovar serotyped at the NRL-Salm.

PMID- 21950219
TI  - Retrospective evaluation of laboratory data on canine vector-borne infections
      from the years 2004-2008.
AB  - The detection and therapy of canine vector-borne diseases in imported dogs are of
      major importance in small animal practice. Over the last years, the import of
      dogs from the Mediterranean region and Southeast Europe has increased, countries
      often endemic for a variety of vector-borne diseases such as babesiosis,
      hepatozoonosis, leishmaniosis, dirofilariosis or ehrlichiosis. This retrospective
      study presents the evaluation of data from our diagnostic laboratory on vector
      borne infections in imported dogs from the years 2004-2008. Specific antibodies
      were detectable in 20.5% of all samples with individual detection rates of 8.9%,
      9.6% and 10.8% for Babesia canis ssp., Leishmania spp. and/or Ehrlichia canis. A
      total of 5.5% of all samples tested by direct methods were positive. Up to 1.1%
      of Giemsa-stained blood/buffy coat smears were positive for B. canis ssp.,
      Rickettsia spp. or Hepatozoon spp. Microfilariae were detectable by the Knott's
      Test in 6.4% and heartworm antigen was detectable using the DiroChek-ELISA in 3%
      of the examined samples. EDTA-blood samples were positive for Leishmania spp.
      (14.9%), E. canis- (5.3%) and A. phagocytophilum-DNA (5.0%) by PCR. Therewith,
      imported dogs have a high chance of being carriers of pathogens. As some diseases
      may also be of a zoonotic concern, in case of the availability of competent
      vectors, the key focus in the future should be aimed at the prevention of
      importing infected dogs or at compulsory diagnostic screening and treatment of
      infected dogs at the time of import.

PMID- 21950220
TI  - [Relevance, measurement and assessment of the antioxidative status in farm
      animals].
AB  - Reactive oxygen species (ROS) are generated in living organisms under
      physiological and pathological conditions. They have to be neutralized by the
      antioxidative system which consists of enzymatic and non enzymatic antioxidants.
      Both, the activity of antioxidative enzymes and the capacity of non enzymatic
      antioxidants are known as the antioxidative status of the organism. If the
      balance between prooxidative processes and antioxidative system is disturbed
      oxidative stress occurs. Oxidative stress is considered to be a major risk factor
      for the reduction of defence mechanisms and development of diseases. The aim of
      the present work is to describe various aspects of the antioxidative status in
      several production animal species. Conclusions for management and therapy are
      drawn when possible. Furthermore the paper provides an overview of methods for
      assessment of antioxidative metabolism. Farm animals undergo several periods of
      severe challenge of the antioxidative system during the production cycle.
      Especially young animals in the first weeks of their life and animals during the
      periparturient period are at high risk. High yielding live stock generally have
      to carry a higher oxidative burden in comparison to animals which are on a medium
      production level or in extensive systems. Other risk factors are unsuitable or
      spoiled components in the diet and heat stress. Exogenous antioxidant supply can
      be optimized by feeding fresh roughage or silage of good quality or if necessary
      by using additives. Changes of the antioxidative system have been described in
      association with displaced abomasum (DA), abomasal volvulus (AV) and reproductive
      problems in swine. Pre- and postoperative supplementation of antioxidants has
      been used with good results as supportive treatment in therapy of cattle with DA.

PMID- 21950221
TI  - Sixty-five years of the Journal Medical Archives.

PMID- 21950222
TI  - Serum lipids and lipoproteins among students of the University of Sarajevo.
AB  - INTRODUCTION: This study researched the distribution of desirable, borderline and
      high-risk values of certain lipid status parameters in healthy young individuals.
      AIM: The purpose of this study was to research the statistical distribution of
      desirable, borderline and high-risk values of certain lipid status parameters in
      healthy young individuals (i.e. medical university students). MATERIAL AND
      METHODS: In this research we tested 112 students studying at the University of
      Sarajevo, of both genders and 20-30 years of age. RESULTS: Total serum
      cholesterol was minimally elevated in 7.1% of tested students, elevated with high
      risk in 2.7% and triglycerides were minimally elevated in 1.8%. Presence of
      elevated LDL cholesterol was found to be 2.7% minimally and 1.8% with high risk.
      HDL cholesterol was minimally decreased in 1 tested student. DISCUSSION: Standard
      biochemical methods were used to determine the values of total cholesterol,
      triglycerides and HDL-cholesterol. The level of LDL cholesterol was also
      calculated. CONCLUSION: Our results point to the need for performing gradual
      laboratory diagnostic procedures for routine check-ups of university students.

PMID- 21950223
TI  - Role of laboratory diagnostic medical biochemistry services -analysis of
      requirements for the laboratory test in the laboratory of primary health care
      center.
AB  - INTRODUCTION: Laboratory diagnosis of medical biochemistry activity plays a
      significant role in the Primary Health Care Center (PHCC), dominated by Family
      medicine and diagnostic services. Medical biochemical diagnosis has a visible
      place at all levels of health care, which shows the number of requests for
      laboratory diagnosis, number and type of required laboratory tests. MATERIALS AND
      METHODS: The study included 1000 requests for laboratory tests at the PHCC in
      Gracanica in primary health care units. We made an analysis of the most common
      laboratory tests in the requests by doctors from primary health care based on
      requests for laboratory diagnosis. RESULTS: The requests of primary health care
      units in PHCC laboratory tests are required at all levels of service: urine, WBC,
      SE, glucose, total bilirubin, ALT, AST, AF, CK, cholesterol, HDL cholesterol,
      triglycerides, creatinine, urea, uric acid, CRP, fibrinogen, calcium and
      phosphorus. The following requirements are the most common laboratory tests with
      94% representation: urine, WBC, glucose, cholesterol, triglycerides,
      aminotransferases, creatinine, and urea. In 1000 requires was required total of
      5333 laboratory tests. Test requirements of a general practice make 44, 1%; FM
      doctors account for 40% and the requirements of other specialists (pediatricians,
      gynecologists and specialists of occupational medicine) are 15, 3%. The doctors
      in family practice most often required: glucose, urine, WBC, SE, TGL., Chol.,
      ALT, AST, creatinine and urea. General practitioners are demanding more
      cholesterol and triglycerides, a family medicine doctors are demanding lower
      cholesterol and triglycerides and higher CRP, fibrinogen, total bilirubin, ALT,
      AST, and other specialists the most demanded urine and WBC. DISCUSSION:
      Laboratory diagnosis is a common diagnosis, which shows the representation of
      required number and type of laboratory tests. In requirements of PHC units in
      PHCC laboratory tests are required at all levels of service: urine, WBC, SE,
      glucose, bilirubin, ALT, AST, AF, CK, cholesterol, HDLchol., triglycerides,
      creatinine, urea, uric acid, CRP, fibrinogen, calcium and phosphorus. The
      following requirements are the most common laboratory tests at the primary level:
      urine, WBC, glucose, cholesterol, urea, and found the secondary level of
      triglycerides, index levels and did not clear the number of searches required by
      the standards and norms of PHC.

PMID- 21950224
TI  - The impact of acute myocardial infarction on left ventricular systolic function.
AB  - BACKGROUND: During acute myocardial infarction left ventricular systolic function
      is an important prognostic factor whose worsening is still frequent despite the
      therapeutic approach. We aimed to estimate the incidence of left ventricular
      systolic dysfunction among patients experiencing acute myocardial infarction.
      METHODS: The study involved 154 consecutive patients admitted at Coronary Care
      Unit. The study design was based upon the collection of patient histories,
      clinical examination and other complementary tests. RESULTS: In overall study
      population, predominantly with male gender, the incidence of left ventricle
      systolic dysfunction was 42.3%, which correlated with myocardial damage,
      electrocardiography changes, myocardial enzymes, and myocardial wall motion.
      CONCLUSIONS: Transthoracic Echocardiography represents a valuable tool and left
      ventricular ejection fraction should be evaluated in all patients experiencing
      acute myocardial infarction since the incidence of left ventricular dysfunction
      in patients with Acute Myocardial Infarction remains relatively high.

PMID- 21950225
TI  - Influence of clonidine on the chemodynamic stability and stress response in the
      course of surgery on general anesthesia.
AB  - This work provides results of therapeutic efficacy testing and clonidine
      toleration in moderating of perioperative tachicardia and hypertension, as well
      as reducing the needs for anaestathic drugs, thus providing better patients'
      cardiovascular stability. MATERIAL AND METHODS: The study involved 60 patients,
      that were subdued to elective non-cardiosurgical operations in general
      anaesthesia. One half of the patients was administred the Clonidine, 0.2
      microg/kg/min in solution, while the other half served as a control group.
      RESULTS: of the study it was evident that the Clonidine group had considerably
      less stress response, which was shown through variaton of cortisol levels during
      operation, glicemy levels and vital parameters. There was a statisticly
      significant difference (p < 0.001) in cortisol serum levels and glicemy beetwen
      these two groups. Complications during anesthesia were fewer in the Clonidine
      group, and the consumption of anesthetic drugs was also lower. CONCLUSION:
      Clonidine effects were favourable during anaesthesia.

PMID- 21950226
TI  - Urinary tract infections in polycystic kidney disease.
AB  - AIM: The aim of this study was to evaluate the bacteriological findings and the
      frequency of urinary tract infections in autosomal dominant polycystic kidney
      disease and their impact on renal function. METHODS: One hundred eighty patients
      with autosomal dominant polycystic kidney disease were studied from 2003 to 2008.
      Subjects were considered as having urinary tract infections if they had had one
      or more episodes of urinary infection. The antibiotic therapy for the treatment
      has been adapted according to the bacteriological findings. RESULTS: Urinary
      tract infections were observed in 60% of our patients (108 patients), and were
      more frequent in women than in men. The infections were typically caused by gram
      negative enteric organisms. Blood culture was positive in 10%, while urine
      culture was negative in 40%. The episodes of isolated cyst infections (negative
      urine culture and absence of white blood cell casts in urinary sediment) were
      more frequent than those of acute or chronic pyelonephritis (urinary sediment was
      positive for white blood cell casts). CONCLUSION: We conclude that urinary tract
      infections are frequent in our patients with autosomal dominant polycystic kidney
      disease. Distinguishing between cyst infection and acute or chronic
      pyelonephritis is often a challenge, and the diagnosis relies mainly on clinical
      and bacteriological findings.

PMID- 21950227
TI  - Assessment of depth of anesthesia: PRST score versus bispectral index.
AB  - Assessment of depth of anesthesia is the basis in anesthesiologists work because
      the occurrence of awareness during general anesthesia is important due to stress,
      which is caused in the patient at that moment, and due to complications that may
      arise later. There are subjective and objective methods used to estimate the
      depth of anesthesia. The aim of this study was to assess the depth of anesthesia
      based on clinical parameters and on the basis bispectral index, and determine the
      part of bispectral monitoring in support to clinical assessment. MATERIAL AND
      METHODS: Sixty patients divided into two groups were analyzed in a prospective
      study. In first group (group 1), the depth of anesthesia was assessed by PRST
      score, and in the second group (group 2) was assessed by bispectral monitoring
      with determination PRST score concurrently. In both groups PRST score was
      assessed in four periods, while bispectral monitoring is used continuously. For
      analysis were used the BIS index values from the equivalent periods as PRST
      scores. PRST score value 0-3, and BIS index 40-60 were considered as adequate
      depth of anesthesia. The results showed that in our study were not waking
      patients during the surgery. In the group where the depth of anesthesia assessed
      clinically, we had a few of respondents (13%) for whom at some point were present
      indicators of light anesthesia. Postoperative interview excluded the possibility
      of intraoperative awareness. In the second group of patients and objective and
      clinical assessment indicated at all times to adequate depth of anesthesia.
      CONCLUSION: The use of BIS monitoring with clinical assessment allows
      anesthesiologists precise decision-making in balancing and dosage of anesthetics
      and other drugs, as well as treatment in certain situations.

PMID- 21950228
TI  - Stress at work and burnout syndrome in hospital doctors.
AB  - INTRODUCTION: Reforming the health care system in Bosnia and Herzegovina began in
      1998 through various forms of amendments to existing health plans and programs.
      There has been the introduction of new technologies, flow of new information from
      the profession, excessive demands on employers, financial constraints, etc. The
      hospital doctors in the workplace suffer from too many stressors. Burnout
      syndrome at work is a form of chronic stress reactions to stressors, and develops
      as a result of inefficient coping with and solving every day, demanding stressful
      situations related to professional duties. GOAL: The goals of this study were: to
      identify the specific stressors of high intensity in the hospital physicians work
      environment, to discover whether and how certain stressors can affect the
      appearance of burnout syndrome at work in a hospital physician, to determine
      whether certain individual factors influence the occurrence of burnout syndrome
      at work. METHODS AND SUBJECTS: We made the intersection study involving the use
      of questionnaires, in order to assess the stressors and burnout syndrome in
      hospital among doctors of the University Clinical Center in Tuzla. RESULTS: The
      study comprised 34.7% hospital doctors (specialists and doctors on
      specialization) of a total 423 employees in various departments of the University
      Hospital Clinical Center in Tuzla. High level of emotional exhaustion was
      recorded in 37.4%, a high level of depersonalization in 45.6%, and a low level in
      perceptions of personal accomplishments in 50.3% of respondents. CONCLUSIONS:
      Continuous exposure to stressors at the workplace, such as work at shifts,
      excessive workload, poor communication with superiors, and lack of continuous
      education of hospital physicians can lead to mental and physical exhaustion,
      professional burnout. Management of the University Clinical Center Tuzla should
      in the future address the structural reorganization of workplaces, as well as
      ongoing prevention interventions in other domains of risk factors or stressors,
      that this study identified.

PMID- 21950229
TI  - Incidence and types of sleep disorders in patients with stroke.
AB  - INTRODUCTION: Sleep disorders (SD) after stroke (stroke) are common occurrences,
      and most often in sleep apnea, insomnia and daytime sleepiness. GOALS. Research
      goals were to determine the types of SD and their frequency in patients with
      stroke in relation to the type of stroke and side of lesion. MATERIALS AND
      METHODS: The study analyzed 200 patients with acute stroke hospitalized in the
      Clinic of Neurology, University Clinical Centre Tuzla in the period from 1st
      August 2007 to 1st June 2008. All patients have confirmed the existence of stroke
      by computerized tomography. SD was verified according to the General Curriculum
      of sleep, the Berlin questionnaire and Epvort scale. Stroke, by type, were
      divided into hemorrhagic and ischemic, and the localization of the stroke to
      right and left cerebral hemispheres. RESULTS: Of the total number of respondents,
      78% had SD. Very serious level of SD had 42% of respondents, 20% moderate, and
      16% of medium-severe degree. There was no statistically significant differences
      in the frequency of SD among patients with ischemic and hemorrhagic stroke
      (76.8%: 82.5%, p = 0.58). In relation to the side of lesion there was more
      patient with SD and stroke in the right cerebral hemisphere, but there were no
      statistically significant differences (39.5%: 33%, p = 0.1). According Epvort
      scale sleep apnea and snoring was present in 86%, daytime sleepiness in 49.5% and
      narcolepsy 0.5%. CONCLUSIONS: Sleep disturbance as a neuropsychological disorder
      has a significant incidence in the acute phase of stroke. SD is slightly more
      common in hemorrhagic stroke and stroke in the right hemisphere. Sleep Apnea and
      snoring are the most common types of SD in patients with stroke.

PMID- 21950230
TI  - Role of renal anemia in the functional, morphological and autoimmune thyroid
      disorders in patients on chronic hemodialysis.
AB  - Thyroid disorders are common in chronic kidney disease. The aim of this study was
      to examine the role of renal anemia on thyroid function, morphology and
      autoimmunity in clinically euthyroid patients on chronic hemodialysis (HD).
      Prospective study during 12 months period included 40 stable patients on chronic
      HD treatment. Patients were divided into two groups according to the serum
      hemoglobin level (group A Hgb > 125 g / L and group B Hgb < 125 g / L). Blood
      samples were taken for determination total and free thyroid hormones, thyroid
      antibodies and standard biochemical tests. Thyroid ultrasonography was performed
      with a 7.5 MHz transducer, 50 mm linear transducer. Thyroid volume was
      calculated, echostructure assessed and presence of nodular changes. In group A,
      was found significantly lower levels of total T3 (1.29 +/- 0469 vs. 1.55 +/-
      0352, p < 0.1); higher prevalence of low T3 syndrome (17.24% (n = 5) vs. 0.00 (n
      = 0), p < 0.05); ultrasound findings suggestive for Hashimoto thyroiditis (13.79
      (n = 4) vs. 0.00% (n = 0), p < 0.05) and multinodular goiter (13.79% (n = 4) vs.
      0.00% (n = 0), p < 0.05). We found no statistically significant difference in the
      mean values of of thyroid antibodies levels, as well as in their percentage
      representation among groups. Morphological, functional and autoimmune disorders
      of thyroid gland are more common in patients on HD with Hgb level < 125 g/L.
      These findings suggest a role of renal anemia in the pathogenesis of these, and
      need for periodical screening of thyroid function, morphology, and titer of
      thyroid antibodies in patients HD, as well as more effective diagnosis and more
      aggressive treatment of renal anemia.

PMID- 21950231
TI  - Evaluation of standardized and applied variables in predicting treatment outcomes
      of polytrauma patients.
AB  - INTRODUCTION: Polytrauma is defined as an injury where they are affected by at
      least two different organ systems or body, with at least one life-threatening
      injuries. Given the multilevel model care of polytrauma patients within KCUS are
      inevitable weaknesses in the management of this category of patients. OBJECTIVE:
      To determine the dynamics of existing procedures in treatment of polytrauma
      patients on admission to KCUS, and based on statistical analysis of variables
      applied to determine and define the factors that influence the final outcome of
      treatment, and determine their mutual relationship, which may result in
      eliminating the flaws in the approach to the problem. MATERIAL AND METHODS: The
      study was based on 263 polytrauma patients. Parametric and non-parametric
      statistical methods were used. Basic statistics were calculated, based on the
      calculated parameters for the final achievement of research objectives,
      multicoleration analysis, image analysis, discriminant analysis and
      multifactorial analysis were used. From the universe of variables for this study
      we selected sample of n = 25 variables, of which the first two modular, others
      belong to the common measurement space (n = 23) and in this paper defined as a
      system variable methods, procedures and assessments of polytrauma patients.
      RESULTS AND DISCUSSION: After the multicoleration analysis, since the image
      analysis gave a reliable measurement results, we started the analysis of
      eigenvalues, that is defining the factors upon which they obtain information
      about the system solve the problem of the existing model and its correlation with
      treatment outcome. CONCLUSION: The study singled out the essential factors that
      determine the current organizational model of care, which may affect the
      treatment and better outcome of polytrauma patients. This analysis has shown the
      maximum correlative relationships between these practices and contributed to
      development guidelines that are defined by isolated factors.

PMID- 21950232
TI  - The hematoma block an effective alternative for fracture reduction in distal
      radius fractures.
AB  - BACKGROUND: An alternative to general anesthesia was tested against hematoma
      block by a double-blind, randomized clinical trial in reduction of Colles
      fracture. METHOD: 96 patients more than 18 years old with displaced fractures of
      distal radius were selected from 2007-2009 on the basis of: 1) informed consent;
      2) no contraindication to any method of analgesia; 3) no associated injury.
      Patients were randomized into 2 equal groups. The A group received Propofol
      intravenously, whereas the B group received 10 ml of 2% Lidocaine Hydrochloride
      into the fracture hematoma. Fractures are reduced under acceptable criteria. Pain
      measured by Visual Analogue Scale (VAS) was recorded before, during, and after
      reduction. Time to Emergency department, to manipulation and to hospital
      discharge is measured. In radiographic before, after reduction and a week later
      the radial tilt, ulnar migration and dorsal tilt are measured. Loss of these
      parameters were study statistically data analysis by KW statistics. RESULTS: 96
      patients with displaced fractures of distal radius at mean age 54.3 (19-84) years
      old, M/F rate 37/59, left/right hand 37/58., from 2005-2008. VAS during reduction
      was 0 in group A and 0.97 +/- 0.7 in group B and VAS after reduction was 2.72 +/-
      0.7 in group A and 2.25 +/- 0.2 in group B. Time to reduction was 2.63 +/- 0.96
      hr in A and 0.90 +/- 0.47 hr in B After a week, 21 fractures lose reduction in
      group A and 22 in group B. CONCLUSION: Hematoma block by local anesthetic is a
      safe and effective alternative to intravenous general anesthesia in reduction of
      Colles fracture.

PMID- 21950233
TI  - Importance of the cytoplasmic super-oxide dismutase in the normal tissue of the
      endometrium and the endometrium carcinoma.
AB  - OBJECTIVES: The objective of the study is comparing pathohistological picture and
      test results of the activity of the enzymes of the anti-oxidative protection 
      cytoplasmic super-oxide dismutase (CuZnSOD) from the blood and endometrium in the
      promotion of the progression or regression of the hyperplasia and endometrium
      carcinoma. MATERIALS AND METHODS: The study has been carried out on 70 patients.
      We have analysed:The age patients, the supersonic test - transvaginal probe,
      pathohistological diagnosis (PHD) analysis of the curet of the patient-we have
      gathered the tissue of the normal and the pathologicaly changed endometrium from
      the exploratory curretage, determining the CuZnSOD in the blood and in the tissue
      of the normal and pathological endometrium of the uterus. The Group A has been
      made out of 30 of them who did not have the irregular bleeding from the uterus,
      and 40 of them represented the Group B with the irregular bleeding, who also had
      PHD confirmed hyperplasia or malign changes of the endometrium. We have tested if
      there has been the pathalogical changes in the small pelvis (the ovary tumor,
      myoma etc.) in both groups. RESULTS: Dominant age in the Group B is 41 - 50
      (55%), in Group A, age difference is not that apparent (p > 0.05). The results of
      the arithmetic mean of the CuZnSOD in the blood (19.90%) and (29.05%) in the
      endometrium which is lower than the Group A (blood-29.95%, endometrium-32.56%).
      Lower values CuZnSOD in the blood (18.9%) and endometrium (30.09%) we have in the
      experimental group patients who have had bleeding as well as those beside
      bleeding had some other gynecological - patological proces (myoma, cyst on the
      ovary etc.) CONCLUSIONS: According to the facts we can see the significance of
      the activity of the enzymes of the anti-oxidative system in the diagnostic of the
      hyperplasia and endometrium carcinoma as well as the possibility of their
      application in the clinical practice.

PMID- 21950234
TI  - The experince with anterior minimally invasive hip surgery.
AB  - Frontal sinus fractures make up about 2-15% of all facial fractures.This is
      relatively low frequency of occurrence, but it has a large potential of
      complication and may involve not only the frontal sinuse but more importantly the
      brain and the eyes. The management depends of the complexity. If anterior wall is
      fractured with grossly involved nasofrontal duct (NFD) in the injury it is
      paramount to occlude NFD. Very often, sinus obliteration is done at the same
      time. In our expirience autogenous cancellous bone graft is considered to be the
      best grafting material. It has the less short - or long-term complications and
      the donor site morbidity is insignificant. KEY

PMID- 21950235
TI  - Managment of frontal sinus fracture: obliteration sinus with cancellous bone
      graft.
AB  - Frontal sinus fractures make up about 2-15% of all facial fractures.This is
      relatively low frequency of occurrence, but it has a large potential of
      complication and may involve not only the frontal sinuse but more importantly the
      brain and the eyes. The management depends of the complexity. If anterior wall is
      fractured with grossly involved nasofrontal duct (NFD) in the injury it is
      paramount to occlude NFD. Very often, sinus obliteration is done at the same
      time. In our expirience autogenous cancellous bone graft is considered to be the
      best grafting material. It has the less short - or long-term complications and
      the donor site morbidity is insignificant.

PMID- 21950236
TI  - Spondylodiscitis due to Sallmonela in an immunocompetent patient.
AB  - Salmonella is a gram-negative bacillus that penetrates in human from contaminated
      food or water. Sallmonela spondylodiscitis is a rare condition occur secondary to
      hematogenous spread after bacteremia episode. We presented a successful treatment
      with Levofloxacin in a 26 years old immunocompetent male with a septic form of
      sallmonelosis complicated with lumbar spondylodiscitis without surgery. He was
      treated with intravenous Levofloxacin for three weeks and was discharged from the
      hospital with oral Levofloxacin for more than two months. Clinical and laboratory
      evaluation two months after oral treatment resulted normal.

PMID- 21950237
TI  - Patents versus patients: must we choose?

PMID- 21950238
TI  - Prizes for innovation of new medicines and vaccines.
AB  - This article argues that prizes can help stimulate medical innovation, control
      costs and ensure greater access to new medicines and vaccines. The authors
      explore four increasingly ambitious prize options to reward medical innovation,
      each addressing flaws in the current patent system. The first option promotes
      innovation through a large prize fund linked to the impact on health outcomes;
      the second option rewards the sharing of knowledge, data, and technology with
      open source dividends; the third option awards prizes for interim benchmarks and
      discrete technical problems; and the final option removes the exclusive right to
      use patented inventions in upstream research in favor of prizes. The authors
      conclude that a system of prizes to reward drug development would break the link
      between R&D incentives and product prices, and that such a reform is needed to
      improve innovation and access to new medicines and vaccines.

PMID- 21950239
TI  - Patents & the progress of personalized medicine: biomarkers research as lens.
AB  - This article addresses the barriers to personalized medicine, focusing on the
      burgeoning field of biomarkers research. The author begins by framing
      intellectual property issues as more than a product of industry incentives and
      suggests that these issues are deeply entangled with other barriers facing
      personalized medicine such as regulatory framework deficiencies. The author
      proposes a set of future research questions to more fully define the barriers to
      biomarkers research and to uncover which corrective measures may be effective.
      The author concludes by recommending an integration of regulatory and patent
      reforms, with a call to action by scholars, scientists, representatives of the
      biopharmaceutical industry, and policy-makers.

PMID- 21950240
TI  - Legal, ethical, and conceptual bottlenecks to the development of useful genomic
      tests.
AB  - This article discusses advances in genomic research in the context of the debate
      surrounding gene patent rights and the limited rights of patient-participants in
      translational research. In addition, the author explores statutory and regulatory
      hurdles to advances in disease diagnosis, such the Bayh-Dole Act, Medicare
      Legislation, and the Health Insurance Portability and Accountability Act. The
      author questions the effectiveness of increasingly commercialized academic
      research and the limited success of the private sector in genomic research. The
      author concludes that future genomic research will require significantly
      increased patient participation, which may necessitate a reshaping of the
      pharmaceutical approach to medicine and the limited stake that patients have in
      the breakthroughs developed through their participation in the process.

PMID- 21950241
TI  - Patents with an "I" = patients.
AB  - The authors address how patent protection in the United States is often quite
      narrow in scope, difficult to obtain, and insufficient in duration, thus stifling
      research and development of potential breakthrough pharmaceuticals. The authors
      further posit that countries that have enacted stronger intellectual property
      rights and research incentives have seen tremendous increases in foreign direct
      investment. In addressing critics of the current patent system, the authors show
      that alternatives to biotechnology patents would not demonstrably improve
      innovation and development of beneficial medicines. The authors conclude that
      given the substantial evidence of the patent system's benefits, and the mere
      speculation that patents have a deleterious effect on patients, no suggestions
      currently proposed to replace or improve the patent system will have the same
      beneficial effects for patients.

PMID- 21950242
TI  - Diseases endemic in developing countries: how to incentivize innovation.
AB  - This comment addresses the inadequacies of research and development for diseases
      endemic in developing countries and explores how the patent system can inhibit
      innovation for new drugs for neglected diseases. The author analyzes four
      strategies to encourage innovation, including open source initiatives, patent
      pools, prizes, and wild card patent extensions, and examines how these
      alternative systems may spur innovation while balancing cost concerns held by
      drug manufacturers and purchasers. The author concludes that a combination of
      solutions may provide the best framework for the creation of essential medicines
      for neglected diseases.

PMID- 21950243
TI  - Ternary rare-earth arsenides REZn3As3 (RE = La-Nd, Sm) and RECd3As3 (RE = La-Pr).
AB  - Ternary rare-earth zinc arsenides REZn(3)As(3) (RE = La-Nd, Sm) with polymorphic
      modifications different from the previously known defect CaAl(2)Si(2)-type forms,
      and the corresponding rare-earth cadmium arsenides RECd(3)As(3) (RE = La-Pr),
      have been prepared by reaction of the elements at 800  degrees C. LaZn(3)As(3)
      adopts a new orthorhombic structure type (Pearson symbol oP28, space group Pnma,
      Z = 4, a = 12.5935(8) A, b = 4.1054(3) A, c = 11.5968(7) A) in which ZnAs(4)
      tetrahedra share edges to form ribbons that are fragments of other layered
      arsenide structures; these ribbons are then interconnected in a three-dimensional
      framework with large channels aligned parallel to the b direction that are
      occupied by La(3+) cations. All remaining compounds adopt the hexagonal
      ScAl(3)C(3)-type structure (Pearson symbol hP14, space group P6(3)/mmc, Z = 2; a
      = 4.1772(7)-4.1501(2) A, c = 20.477(3)-20.357(1) A for REZn(3)As(3) (RE = Ce, Pr,
      Nd, Sm); a = 4.4190(3)-4.3923(2) A, c = 21.4407(13)-21.3004(8) A for RECd(3)As(3)
      (RE = La-Pr)) in which [M(3)As(3)](3-) layers (M = Zn, Cd), formed by a triple
      stacking of nets of close-packed As atoms with M atoms occupying tetrahedral and
      trigonal planar sites, are separated by La(3+) cations. Electrical resistivity
      measurements and band structure calculations revealed that orthorhombic
      LaZn(3)As(3) is a narrow band gap semiconductor.

PMID- 21950244
TI  - Metabolic profiling based on two-dimensional J-resolved 1H NMR data and parallel
      factor analysis.
AB  - Metabolic profiling of natural products is used to map correlated concentration
      variances of known and unknown secondary metabolites in extracts. NMR
      spectroscopy is in this respect regarded as a convenient and reproducible
      technique with the ability to detect a wide range of small organic compounds. Two
      dimensional J-resolved NMR-spectra are used in this context to resolve
      overlapping signals by separating the effect of J-coupling from the effect of
      chemical shifts. Often one-dimensional projections of these data are used as
      input for standard multivariate statistical methods, and only the intensity
      variances along the chemical shift axis are taken into account. Here, we describe
      the use of parallel factor analysis (PARAFAC) as a tool to preprocess a set of
      two-dimensional J-resolved spectra with the aim of keeping the J-coupling
      information intact. PARAFAC is a mathematical decomposition method that fits
      three-way experimental data to a model whose parameters in this case reflect
      concentrations and individual component spectra along the chemical shift axis and
      corresponding profiles along the J-coupling axis. A set of saffron samples,
      directly extracted with methanol-d(4), were used as a model system to evaluate
      the feasibility and merits of the method. To successfully use PARAFAC, the two
      dimensional spectra (n = 96) had to be aligned and processed in narrow windows
      (0.04 ppm wide) along the chemical shift axis. Selection of windows and number of
      components for each PARAFAC-model was done automatically by evaluating amount of
      explained variance and core consistency values. Score plots showing the
      distribution of objects in relation to each other, and loading plots in the form
      of two-dimensional pseudospectra with the same appearance as the original J
      resolved spectra but with positive and negative contributions are presented.
      Loadings are interpreted not only in terms of signals with different chemical
      shifts but also the associated J-coupling profiles.

PMID- 21950245
TI  - Highly tunable self-assembled nanostructures from a poly(2-vinylpyridine-b
      dimethylsiloxane) block copolymer.
AB  - An extraordinarily large degree of tunability in geometry and dimension is
      demonstrated in films of a self-assembled block copolymer. A poly(2-vinylpyridine
      b-dimethylsiloxane) block copolymer with highly incompatible blocks was spun-cast
      on patterned substrates and treated with various solvent vapors. The degree of
      selective swelling in the poly(2-vinylpyridine) matrix block could be controlled
      over an extensive range, leading to the formation of various microdomain
      morphologies such as spheres, cylinders, hexagonally perforated lamellae, and
      lamellae from the same block copolymer. The systematic control of swelling ratio
      and the choice of solvent vapors offer the unusual ability to control the width
      of very well-ordered linear features within a range between 6 and 31 nm. This
      methodology is particularly useful for nanolithography based on directed self
      assembly in that a single block copolymer film can form microdomains with a broad
      range of geometries and sizes without the need to change molecular weight or
      volume fraction.

PMID- 21950246
TI  - Penetration pattern of rhodamine dyes into enamel and dentin: confocal laser
      microscopy observation.
AB  - Enamel and dentin are susceptible to extrinsic and intrinsic stains. The purposes
      of this study were to determine the penetration pattern of Rhodamine B and
      dextran-conjugated Rhodamine B into the enamel and dentin as observed by confocal
      laser microscopy and to relate it to the penetration pattern of hydrogen peroxide
      commonly used as an active ingredient in tooth-whitening agents and high
      molecular-weight staining molecules. Eighteen recently extracted human maxillary
      anterior teeth were used. Teeth were cleaned and painted with nail varnish except
      for the crown area above the cemento-enamel junction (CEJ). The painted teeth
      were then immersed in Rhodamine B and dextran-conjugated Rhodamine B (70 000 MW)
      for 4, 7, 10 and 15 days. Teeth were sliced to 3 mm thickness in transverse plane
      and mounted on a glass slide just prior to observation with confocal laser
      microscopy. Rhodamine B and dextran-conjugated Rhodamine B readily penetrated
      into the enamel and dentin when exposed for 4 and 7 days, respectively. Rhodamine
      B penetrated along the interprismatic spaces of the enamel into the dentin. The
      penetration was accentuated in sections with existing crack lines in the enamel.
      Rhodamine B was readily absorbed into the dentinal tubules at the dentino-enamel
      junction and continued to penetrate through the dentin via the dentinal tubules
      into the pre-dentin. Within the limitations of this study, it is concluded that
      Rhodamine B and dextran-conjugated Rhodamine B when applied to the external
      surface of the tooth readily penetrate into the enamel and dentin via the
      interprismatic spaces in the enamel and dentinal tubules in the dentin,
      suggesting that stain molecules and bleaching agents possibly exhibit similar
      penetration pathways.

PMID- 21950247
TI  - Presidential address. The American Society of Parasitologists: who are we now?

PMID- 21950248
TI  - Emergency contraceptive pill (ECP) use and experiences at college health centers
      in the mid-Atlantic United States: changes since ECP went over-the-counter.
AB  - OBJECTIVE: To investigate the availability of emergency contraceptive pills
      (ECPs) at college health centers since ECP went over-the-counter (OTC) in 2006.
      Related issues, such as distribution procedure, existence of a written protocol,
      personnel involved, contraindications, follow-up procedures, methods of
      advertising, and staff attitudes, were examined. PARTICIPANTS: The sample
      included 135 college and university health centers in the mid-Atlantic region of
      the United States. METHODS: Data were collected via telephone survey with the use
      of a 42-item survey instrument. RESULTS: Forty-three percent of schools reported
      distributing ECPs, for an average of 10.6 years. Major changes in ECP
      distribution and usage since ECP went OTC related primarily to protocol in ECP
      distribution, advertising for ECP services, and ECP accessibility to university
      students. CONCLUSIONS: College health centers are responding to the OTC status of
      ECP in a number of ways, primarily relating to their distribution procedures and
      advertising techniques.

PMID- 21950249
TI  - Nonsuicidal self-injury in a college population: general trends and sex
      differences.
AB  - OBJECTIVE: To describe basic nonsuicidal self-injury (NSSI) characteristics and
      to explore sex differences. METHODS: A random sample from 8 universities were
      invited to participate in a Web-based survey in 2006-2007; 38.9% (n = 14,372)
      participated. Analysis assessed sex differences in NSSI prevalence, practices,
      severity, perceived dependency, and help-seeking; adjusted odds ratios for NSSI
      characteristics were calculated by sex status. RESULTS: Lifetime NSSI prevalence
      rates averaged 15.3%. Females were more likely than males to self-injure because
      they were upset (adjusted odds ratio [AOR] = 1.6; 95% confidence interval [CI] =
      1.3-2.1) or in hopes that someone would notice them (AOR = 1.6, 95% CI = 1.1
      2.7). Males were 1.6 times (95% CI = 1.2-2.2) more likely to report anger and 4.0
      times (95% CI = 2.3-6.8) more likely to report intoxication as an initiating
      factor. Sexual orientation predicted NSSI, particularly for women (Wald F = 8.81,
      p <= .000). Only 8.9% of the NSSI sample reported disclosing NSSI to a mental
      health professional. CONCLUSIONS: NSSI is common in college populations but
      varies significantly by sex and sexual orientation. NSSI disclosure is low among
      both sexes.

PMID- 21950250
TI  - Eating disorder symptoms among college students: prevalence, persistence,
      correlates, and treatment-seeking.
AB  - OBJECTIVE: To examine the prevalence, correlates, persistence, and treatment
      seeking related to symptoms of eating disorders (EDs) in a random sample of
      college students. PARTICIPANTS: A random sample of students at a large university
      were recruited for an Internet survey in Fall 2005 and a follow-up survey in Fall
      2007. METHODS: ED symptoms were measured using the SCOFF screen and adjusted for
      nonresponse using administrative data and a nonresponse survey. RESULTS: 2,822
      (56%) students completed the baseline survey. Among undergraduates the prevalence
      of positive screens was 13.5% for women and 3.6% for men. Among students with
      positive screens, 20% had received past-year mental health treatment. In the
      follow-up sample (N = 753), ED symptoms at baseline significantly predicted
      symptoms 2 years later. CONCLUSIONS: Symptoms of EDs were prevalent and
      persistent among college students in this study. These findings suggest that
      brief screens can identify a large number of students with untreated EDs.

PMID- 21950251
TI  - College students and condom attitude: validation of the Multi-Factor Attitude
      toward Condoms Scale (MFACS).
AB  - OBJECTIVE: Sexually transmitted infections and the human immunodeficiency virus
      incidence rates remain high among college-aged individuals. This study examined
      the validity and reliability of the Multi-Factor Attitude toward Condoms Scale
      (MFACS). PARTICIPANTS: Participants were recruited from a large midwestern
      university during February and March 2009. METHODS: Data were collected using in
      class data collection with a test-retest design from undergraduate courses. A
      total of 442 surveys were collected during initial testing and 421 during
      retesting. RESULTS: Reliability assessments indicated a sufficient Cronbach's
      alpha for the total scale (alpha = .805) and each subscale: affective (alpha =
      .790), perceived effectiveness (alpha = .795), and manageability (alpha = .751).
      Further analyses provide evidence of construct validity. CONCLUSIONS: The study
      reaffirmed the psychometric properties of the MFACS among a sample of college
      students. The MFACS provides a contemporary way to examine condom attitudes as
      sexual health research is moving beyond only disease prevention efforts.

PMID- 21950252
TI  - Depressive symptoms and mental health treatment in an ethnoracially diverse
      college student sample.
AB  - OBJECTIVES: To study (a) the prevalence of depressive symptoms and (b) the
      utilization of mental health treatment in an ethnoracially diverse sample
      consisting primarily of Asian Americans, European Americans, Native Hawaiians,
      and Pacific Islanders. PARTICIPANTS: Five hundred eighty-nine college students.
      METHOD: A questionnaire packet that included the Center for Epidemiological
      Studies Depression Scale (CES-D) was administered to students in introductory
      psychology courses. RESULTS: (a) There were no differences among ethnoracial
      groups in levels of depressive symptoms as measured by the CES-D; (b) 71% of
      participants with high levels of depressive symptoms had not received any mental
      health treatment in the previous 12 months; and (c) European Americans were 3.7
      times more likely to have received mental health treatment in the previous 12
      months than other students. CONCLUSION: Outreach efforts designed to improve
      utilization of mental health treatment services by depressed college students,
      especially by members of ethnoracial minority groups, should be increased.

PMID- 21950253
TI  - What matters most? Assessing the influence of demographic characteristics,
      college-specific risk factors, and poly-drug use on nonmedical prescription drug
      use.
AB  - OBJECTIVE: Although prior recent research has revealed a significant relationship
      between the nonmedical use of prescription drugs, demographic characteristics,
      college-specific risk factors, and other substance use among college students,
      there remains a need to conduct a comparative analysis on the differential impact
      these factors may have on predicting nonmedical prescription drug use.
      PARTICIPANTS AND METHODS: In 2008 a convenience sample of 599 undergraduate
      students attending a southeastern university completed a self-report survey
      measuring substance use behaviors. RESULTS: Males, Greeks, and freshman were more
      likely than females, non-Greeks, and upperclassman to use nonmedical prescription
      drugs in the past year. Multivariate analyses, however, indicate that the
      excessive use of alcohol and other illicit drugs are more influential than
      demographic and college-specific risk factors. CONCLUSION: Poly-drug use was
      found to be the most significant predictor of the use of nonmedical prescription
      drugs as compared to demographic and college-specific risk factors.

PMID- 21950254
TI  - Social control of healthy behavior between intimate college students.
AB  - OBJECTIVE: The author examined whether the type of intimacy (i.e., emotional,
      intellectual, sexual, social, recreational) featured in college students'
      romantic relationships affects the extent to which a partner's health-related
      behavior may be influenced by a variety of behavior change appeals. PARTICIPANTS:
      One hundred and thirteen female and 94 male college students were surveyed.
      METHODS: A questionnaire sought demographic information and included 2 scales to
      determine intimacy type levels and estimated responses to behavior change
      appeals. RESULTS: It was determined that emotional and intellectual intimacy had
      the greatest effects on compliance estimates. The liking strategy was rated as
      generally most effective, whereas caring fared better in highly intimate
      relationships, and both threat and responsibility appeals functioned better in
      relationships featuring lower levels of intimacy. CONCLUSIONS: When appropriately
      qualified as initial findings, the outcomes may suggest routes to successfully
      inspiring particular health behavior changes, especially among partners in
      emotionally and intellectually intimate relationships.

PMID- 21950255
TI  - Assessing university students' self-efficacy to employ alcohol-related harm
      reduction strategies.
AB  - OBJECTIVE: Develop and evaluate key psychometric properties of a self-report
      questionnaire specifically designed to assess student drinkers' self-confidence
      to employ a variety of strategies intended to reduce unhealthy consequences of
      high-risk drinking. METHODS: Four hundred ninety-eight participants rated their
      confidence (from "not at all confident" to "completely confident") to employ 17
      harm reduction strategies when drinking. RESULTS: Factor analysis and internal
      consistency reliability analyses indicated that the 17 items constitute a single
      scale with good test-retest reliability. Consistent with other research examining
      previous use of such strategies, women in our sample reported significantly
      higher harm reduction self-efficacy than did men. Harm reduction self-efficacy
      was also associated with reported number of high-risk drinking episodes in the
      previous 2 weeks. CONCLUSION: This brief and easily administered questionnaire
      holds promise as a clinical tool to identify individuals with low harm reduction
      self-efficacy and as an outcome measure for health promotion and educational
      interventions.

PMID- 21950256
TI  - Sexual and reproductive health behaviors of California community college
      students.
AB  - OBJECTIVE: To explore the sexual and reproductive health behaviors of students
      from 13 community college campuses in California. PARTICIPANTS: Heterosexual
      college students, ages 18 to 24, who have had sexual intercourse (N = 4,487).
      METHODS: The American College Health Association's National College Health
      Assessment (ACHA-NCHA) survey was administered in class to randomly selected
      classrooms at 12 institutions and electronically to randomly selected e-mails of
      students at 1 institution from March through April 2007. RESULTS: This sample of
      community college students reported higher rates of risky sexual behaviors,
      unintended pregnancy, emergency contraception, and sexually transmitted diseases,
      and lower rates of human immunodeficiency virus (HIV) testing, than the overall
      ACHA-NCHA reference group. Those who had been tested for HIV reported more sexual
      partners, and lower rates of condom use. CONCLUSIONS: The data provide
      justification for broader educational programs and access to family planning
      services, condoms, and HIV testing on community college campuses.

PMID- 21950257
TI  - Peer influence: use of alcohol, tobacco, and prescription medications.
AB  - OBJECTIVE: Risk-taking behavior (e.g., alcohol abuse, tobacco usage, misuse of
      prescription medications) among college students is a widespread problem. This
      study focused not only on the frequency of risky health behaviors in college
      students, but also the companions with whom they engaged in such behaviors.
      METHODS: Three hundred and twelve college students completed a survey examining
      the frequency with which they engaged in alcohol, tobacco, and improper
      prescription medication use, as well as with whom they were most likely to engage
      in these behaviors. RESULTS: Results indicated that participants were most likely
      to take health risks when accompanied by someone they consider a friend. Results
      also indicated gender differences in risk-taking behaviors, as well as an
      interaction effect between companion and gender. CONCLUSIONS: This information
      would be useful when developing preventive interventions for college students.
      Implementing interventions that are specific to certain populations might
      generate greater success in reducing risk-taking behavior.

PMID- 21950258
TI  - Chiari type I malformations in young adults: implications for the college health
      practitioner.
AB  - The authors describe 2 cases of Chiari type I malformation (CM-I) in students
      presenting to a college health center within a 6-month period. A review of CM-I,
      including epidemiology, typical presentation, evaluation, and management, is
      followed by a discussion of the clinical and functional implications of the
      disorder in an emerging adult population.

PMID- 21950259
TI  - A collaborative university model for employee wellness.
AB  - Universities are taking a more active approach in understanding and monitoring
      employees' modifiable health risk factors and chronic care conditions by
      developing strategies to encourage employees to start and sustain healthy
      behaviors. WellBama, the University of Alabama's signature health and wellness
      program, utilizes a collaborative model in partnership with select colleges and
      departments to implement strategies to improve employees' health status. The
      program provides onsite health screenings and assessments, timely health advising
      sessions, assistance in setting and monitoring individual health goals to promote
      improved health, and preventive examination referrals.

PMID- 21950260
TI  - Strategies for implementing a tobacco-free campus policy.
AB  - This report examines the rationale for creating a tobacco-free campus to utilize
      in passing antitobacco policies, and recommendations for overcoming barriers. As
      with any type of advocacy effort, a variety of impediments exist, including lack
      of administrative and staff support, absence of student involvement, and sparse
      resources. A variety of potential remedies and advocacy opportunities are
      explored and delineated.

PMID- 21950261
TI  - Adoption of an outdoor residential Hall smoking policy in a California public
      university: a case study.
AB  - OBJECTIVE: Because secondhand smoke is a public health concern, many colleges
      have adopted bans to ensure healthier environments. This study demonstrates how
      outdoor smoking policy change can be accomplished at a large public university.
      PARTICIPANTS: The participants were 1,537 students housed in residential
      communities at the University of California, Berkeley, who completed an online
      survey. METHODS: A proposal for smoke-free residential communities that included
      student resident survey data was prepared. RESULTS: The survey data indicated
      that most students (77%) were bothered by secondhand smoke, and most (66%)
      favored smoke-free environments. The data were used to advocate for a change in
      the residential community smoking policy. CONCLUSION: The survey data and
      institutional comparisons played a key role in administrators' decision-making
      about campus smoking policy. Despite administrators' concerns about students'
      safety and freedom of choice, student-led advocacy was able to influence policy
      change.

PMID- 21950262
TI  - Response to letter to the editors: "Non-group a streptococci as common isolates
      on throat culture among college students with pharyngitis".

PMID- 21950264
TI  - Sweets, sex, or self-esteem? Comparing the value of self-esteem boosts with other
      pleasant rewards.
AB  - Many people ascribe great value to self-esteem, but how much value? Do people
      value self-esteem more than other pleasant activities, such as eating sweets and
      having sex? Two studies of college students (Study 1: N=130; Study 2: N=152)
      showed that people valued boosts to their self-esteem more than they valued
      eating a favorite food and engaging in a favorite sexual activity. Study 2 also
      showed that people valued self-esteem more than they valued drinking alcohol,
      receiving a paycheck, and seeing a best friend. Both studies found that people
      who highly valued self-esteem engaged in laboratory tasks to boost their self
      esteem. Finally, personality variables interacted with these value ratings.
      Entitled people thought they were more deserving of all pleasant rewards, even
      though they did not like them all that much (both studies), and people who highly
      value self-esteem pursued potentially maladaptive self-image goals, presumably to
      elevate their self-esteem (Study 2).

PMID- 21950265
TI  - Rotenone-mediated changes in intracellular coenzyme A thioester levels:
      implications for mitochondrial dysfunction.
AB  - Rotenone, an organic pesticide and potent mitochondrial complex I inhibitor,
      causes Parkinson-like neurodegeneration in rodents and is implicated in human
      Parkinson's disease. In this rapid report, rotenone induced a dose-dependent
      decrease in succinyl-coenzyme A (CoA) and increase in beta-hydroxybutyryl-CoA in
      multiple human cell lines (IC(50) < 100 nM). Rotenone also inhibited [U-(13)C(6)]
      glucose-derived [(13)C]-acetyl-CoA and [(13)C]-succinyl-CoA biosynthesis in SH
      SY5Y neuroblastoma cells. These changes are compatible with a compensatory
      metabolic rearrangement. Stable isotope dilution liquid chromatography-mass
      spectrometry and CoA thioester isotopomer analysis provided insight into
      mechanisms of rotenone toxicity, which will facilitate the development of new
      biomarkers of mitochondrial dysfunction.

PMID- 21950266
TI  - KL-6: a serological biomarker for interstitial lung disease in patients with
      polymyositis and dermatomyositis.
AB  - OBJECTIVES: To investigate whether Caucasian patients with polymyositis (PM) or
      dermatomyositis (DM) and interstitial lung disease (ILD) have elevated serum
      levels of KL-6 compared with patients without ILD and whether KL-6 could be used
      as a marker for ILD activity and treatment efficacy of ILD in PM/DM. DESIGN AND
      METHODS: Thirty patients with PM/DM (seven with ILD) and 17 age- and sex-matched
      healthy controls were included in a retrospective, cross-sectional analysis.
      Twelve patients were followed for longitudinal evaluation. ILD was defined as
      restrictive lung function impairment with radiographic signs of ILD. Serum KL-6
      levels were measured using a sandwich enzyme immunoassay kit. Groups were
      compared by Mann-Whitney U-test. RESULTS: PM/DM patients with ILD had
      significantly higher median serum KL-6 levels compared with those without ILD:
      995 (range 533-2318) versus 322 (range 132-1225) U mL(-1) (P = 0.0002). Median
      serum levels of healthy controls were 225 (range 136-519) U mL(-1) . Serum levels
      of KL-6 were inversely correlated with percentages of forced expiratory volume in
      1 s (FEV1), vital capacity (VC), total lung capacity (TLC), forced VC, diffusing
      capacity of carbon monoxide (DLco), maximal voluntary ventilation at 40 breaths
      min(-1) and residual volume (RV). Changes in KL-6 levels showed a significant
      inverse correlation with changes in percentage FEV1, TLC, DLco and RV. At a cut
      off level of 549 U mL(-1) (mean +/- 2.5 SD for controls), the sensitivity and
      specificity for diagnosis of ILD were 83% and 100%, respectively. CONCLUSION: The
      level of serum KL-6 may serve as measure of ILD in patients with PM/DM and is a
      promising biomarker for use in clinical practice to assess clinical response to
      treatment.

PMID- 21950267
TI  - Oral immunotherapy with immunodominant T-cell epitope peptides alleviates
      allergic reactions in a Balb/c mouse model of egg allergy.
AB  - BACKGROUND:   Allergen-specific T-cell epitopes are obvious targets for
      immunotherapeutic interventions in allergic disease. T-cell epitope peptides
      given orally may provide a practical way of inducing tolerance and preventing
      allergy. OBJECTIVE:   This study investigates oral immunotherapy (OIT) with T
      cell epitope peptides of the dominant egg-white allergen ovomucoid (Ovm) in a
      Balb/c mouse model of egg allergy. METHODS:   Groups of mice were orally
      sensitized to Ovm and subsequently administered Ovm T-cell epitopes [single
      peptide 157-171 (SP) or multiple peptide (157-171)(3) (MP)], followed by oral
      challenge with Ovm. Outcomes post oral challenge were measured as clinical signs,
      serum histamine, antibody activity (IgG, IgE, IgG1, IgG2, IgA), cytokines (IL-4,
      IFN-gamma, IL-12p70, IL-10, TGF-beta, and IL-17), and T regulatory cells (Tregs).
      RESULTS:   Clinical signs were less frequent in both SP and MP groups (P <=
      0.05). Specific IgE was less and IgA was more in both groups; however, SP-treated
      mice had less histamine and IgG1 and more IgG2-related antibodies indicating a
      bias toward the type-1 response (P <= 0.05). Concentration of type-2 cytokine
      interleukin-4 (IL-4) was significantly less in both groups and IL-12p70 and IL-10
      were more in SP-treated mice (P <= 0.001). Interferon-gamma, IL-17, and TGF-beta
      did not differ significantly. There was significant increase in the percentage of
      CD4+FOXP3+ and CD4+CD25+ cells in the SP group, indicating the significant role
      of Tregs in immune regulation. CONCLUSION:   In summary, we demonstrated that OIT
      with SP and MP comprising the immunodominant regions of Ovm was safe and
      significantly reduced subsequent frequency of allergy to Ovm, and validated
      potential use of Ovm T-cell epitope as an immunoregulator.

PMID- 21950268
TI  - Long-term patency of saphenous vein patch plasty for left main coronary artery
      ostial disease.

PMID- 21950269
TI  - Recommendations for the prevention of pregnancy-associated venous
      thromboembolism.
AB  - Pregnancy is a risk factor for venous thromboembolism (VTE), an important cause
      of maternal morbidity and mortality. Although there is a 4-5-fold increased risk
      compared to that of nonpregnant women of the same age, the absolute risk is low
      at no more than two episodes of VTE per 1000 pregnancies. There is uncertainty
      about which women require thromboprophylaxis during pregnancy or postpartum
      because of a lack of data from appropriate clinical trials. For this reason,
      recommendations for prophylaxis should be made only after explaining the
      available evidence to the patient and taking into account her perception of the
      balance of risk and benefit in thromboprophylaxis. The aim of these
      recommendations is to provide clinicians with practical advice to assist in
      decisions regarding thromboprophylaxis in women considered to be at risk of VTE
      during pregnancy and the postpartum. The authors are clinicians from across New
      Zealand and Australia representing the fields of haematology, obstetric medicine,
      anaesthesiology, maternal-fetal medicine and obstetrics. Authors were invited to
      review the relevant literature and then worked collaboratively to devise
      recommendations and resolve areas of controversy. The recommendations contained
      herein were reached by consensus and represent the opinion of the panel. The
      absence of randomised clinical trials in this area limits the strength of
      evidence that can be used, and it is acknowledged that they represent level C
      evidence. The panel advocates for appropriate clinical studies to be carried out
      in this patient population to address the inadequacy of present evidence.

PMID- 21950270
TI  - Assessing the neurophysiological effects of botulinum toxin treatment for adults
      with focal limb spasticity: a systematic review.
AB  - To examine effectiveness of botulinum toxin therapy (BoNT), accurate
      quantification of the neurological component of underlying spasticity is needed.
      PURPOSE: Systematically identify and summarize literature on neurophysiological
      methods to test the effectiveness of BoNT, discuss methodological aspects, and
      recommend best techniques for clinical and research settings. METHODS: Electronic
      databases were searched using specific keywords. Reviews and reference lists were
      hand-checked to find relevant studies. Studies in adults with focal limb
      spasticity were included. RESULTS: Over 300 articles were scanned for relevance,
      and a list of 90 relevant articles was made. After excluding reviews and studies
      in healthy controls or non-spasticity related BoNT, 22 articles were reviewed.
      Neurophysiological techniques included electromyography (EMG; n = 11), electrical
      nerve stimulation (n = 13), transcranial magnetic stimulation (TMS; n = 1),
      functional magnetic resonance imaging (fMRI; n = 1), reflex threshold (n = 4),
      Achilles tendon reflex (n = 1), reflex latency (n = 1). DISCUSSION: Maximum M
      wave amplitude (M-max) and stretch reflex threshold techniques were successfully
      used to measure the neurophysiological effects of BoNT and have high test-retest
      reliability. EMG techniques require effective magnitude normalization techniques
      and establishing test-retest reliability. CONCLUSION: Serial electrical nerve
      stimulation can be incorporated into clinical practice to assist in follow-up. We
      recommend using M-max and stretch reflex threshold techniques to assess the
      neurophysiological effects.

PMID- 21950272
TI  - Sexual antagonism for testosterone maintains multiple mating behaviour.
AB  - 1. The persistence of multiple mating remains one of the fundamental questions in
      evolutionary biology. In theory, multiple mating is predicted to improve female
      fitness cumulatively through direct and/or genetic benefits. However, intra-locus
      sexual conflicts may potentially constrain or even eliminate these benefits owing
      to the gender load imposed by sexually antagonistic selection. 2. Here, we tested
      whether sexually antagonistic selection can maintain the variance in multiple
      mating behaviour of bank voles (Myodes glareolus) by manipulating the hormone
      testosterone through artificial selection in the laboratory. Among mammals,
      testosterone is a sexually dimorphic fitness-related trait under selection and is
      known to affect mating behaviour. We conducted mating trials in which females
      derived from family-based selection of testosterone were sequentially paired with
      four males of different testosterone profiles. 3. We show that artificial
      selection for high testosterone increased the mating rate of males, but clearly
      decreased the number of partners that females mated with (and vice versa).
      Because multiple mating was beneficial for the reproductive success of both
      sexes, as evidenced by the positive Bateman gradients, the divergent evolutionary
      interests of testosterone between the sexes can maintain this polygynandrous
      mating system. 4. Our results highlight how mating rate is concordantly selected
      in both sexes; however, it is largely influenced by testosterone, which is under
      sexually antagonistic selection. 5. This study is the first one to emphasise the
      direct and indirect effects of the endocrine system not only on reproductive
      physiology and behaviour but also for the evolution of genetic mating strategies
      in mammals.

PMID- 21950273
TI  - Case of necrobiosis lipoidica diabeticorum successfully treated by photodynamic
      therapy.

PMID- 21950274
TI  - HIV testing in women: missed opportunities.
AB  - OBJECTIVE: To investigate opportunities for early human immunodeficiency virus
      (HIV) testing of women. METHODS: A retrospective cohort study design linked case
      reports from HIV surveillance to several statewide health-care databases. Medical
      encounters occurring before the first positive HIV test (missed opportunities)
      were categorized by diagnosis/procedure codes to distinguish visits that were
      likely to have prompted an HIV test. Women were categorized as late testers (AIDS
      diagnosis <12 months from first HIV test date), non-late testers (no AIDS
      diagnosis during study period or diagnosis of AIDS >12 months of HIV diagnosis),
      of reproductive age (13-44 years old), and not of reproductive age (>44 years
      old). Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were used to
      estimate risk and its statistical significance. RESULTS: Of 3303 HIV-infected
      women diagnosed during the study period, 2408 (73%) had missed opportunity
      visits. Late testers (39%) were more likely to be black than white (aOR 1.48, 95%
      CI 1.12-1.95), be older (>44 years old; aOR 7.85, 95% CI 4.49-13.7), and have >10
      missed opportunity visits (aOR 2.17, 95% CI 1.62-2.91). Fifty-four percent of
      women >44 years old were also late testers. Women >44 years old had lower median
      initial CD4 counts (p<0.001). The top two procedures were the same for all groups
      of women but mammography was ranked fourth for women >44 years old and
      Papanicolau smear was ranked fourth for late testers. CONCLUSIONS: Feasibility
      and acceptability of routine HIV testing in nontraditional health-care settings,
      such as mammography and Papanicolau screenings, should be explored to identify
      late testers and older (not of reproductive age) HIV-infected women.

PMID- 21950271
TI  - Microbe-I: fungal biota analyses of the Japanese experimental module KIBO of the
      International Space Station before launch and after being in orbit for about 460
      days.
AB  - In addition to the crew, microbes also find their way aboard the International
      Space Station (ISS). Therefore, microbial monitoring is necessary for the health
      and safety of the crew and for general maintenance of the facilities of this
      station. Samples were collected from three sites in the Japanese experimental
      module KIBO on the ISS (air diffuser, handrail, and surfaces) for analysis of
      fungal biota approximately 1 year after this module had docked with the ISS.
      Samples taken from KIBO before launch and from our laboratory were used as
      controls. In the case of KIBO, both microbe detection sheet (MDS) and swab
      culture tests of orbital samples were negative. The MDS were also examined by
      field emission-scanning electron microscopy; no microbial structures were
      detected. However, fungal DNAs were detected by real-time PCR and analyzed by the
      clone library method; Alternaria sp. and Malassezia spp. were the dominant
      species before launch and in space, respectively. The dominant species found in
      specimens from the air conditioner diffuser, lab bench, door push panel, and
      facility surfaces on our laboratory (ground controls) were Inonotus sp.,
      Cladosporium sp., Malassezia spp., and Pezicula sp., respectively. The fungi in
      the KIBO were probably derived from contamination due to humans, while those in
      our laboratory came from the environment (e.g., the soil). In conclusion, the
      cleanliness in KIBO was equivalent to that in a clean room environment on the
      ground.

PMID- 21950284
TI  - Effect of vardenafil on nitric oxide synthase expression in the paraventricular
      nucleus of rats without sexual stimulation.
AB  - Vardenafil hydrochloride (HCl) is a potent and selective phosphodiesterase type-5
      (PDE-5) inhibitor that enhances nitric oxide (NO)-mediated relaxation of human
      corpus cavernosum and NO-induced rabbit penile erection, and enhances erectile
      function in patients. In the present study, the effect of vardenafil on nitric
      oxide synthase (NOS) and neuronal NOS expressions in the paraventricular nucleus
      (PVN) of rats without sexual stimulation was investigated using nicotinamide
      adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry and neuronal
      NOS (nNOS) immunohistochemistry and western blot analysis. The present results
      showed that NOS and nNOS expression in the PVN was increased by vardenafil
      treatment as the dose- and duration-dependently without sexual stimulation. The
      phosphodiesterase type-5 inhibitor, vardenafil, augmented NOS expression in the
      brain without sexual stimulation. The present study suggests that sexual
      behaviour can be directly modulated by neurotransmitters such as nitric oxide.

PMID- 21950285
TI  - Treatment of acne scarring.
AB  - BACKGROUND: Post-acne scarring remains a common entity despite advances in the
      treatment of acne. This represents limitations in our quality of therapy and a
      failure of public education. The level of severe scarring remains as much an
      ongoing challenge to prevent as well as manage. METHODS: This review will
      concentrate on the methods by which acne scarring may be improved and the
      available evidence for their utility. It will also rely on a grading scale of
      disease burden to classify patients and their ideal therapy. New therapies
      allowing treatment of scarring in areas other than the face will also be
      highlighted. RESULTS: Tabulated treatment planning will present algorithms
      summarizing best practice in the treatment of post-acne scarring. CONCLUSION:
      Post-acne scarring is being better managed. Grade 1 scars with flat red, white,
      or brown marks are best treated with topical therapies, fractionated and pigment
      or vascular-specific lasers and, occasionally, pigment transfer techniques. Grade
      2 mild scarring as seen primarily in the mirror is now the territory of non
      ablative fractionated and non-fractionated lasers as well as skin rolling
      techniques. Grade 3 scarring, visible at conversational distance but distensible,
      is best managed by traditional resurfacing techniques or with fractional non
      ablative or ablative devices, sometimes including preparatory surgical
      procedures. Grade 4 scarring, where the scarring is at its most severe and non
      distensible, is most in need of a combined approach.

PMID- 21950286
TI  - Acrodermatitis continua of Hallopeau: evolution of treatment options.
AB  - Ever since its inception, acrodermatitis continua of Hallopeau, has been
      recognized as an uncommon clinical entity which has been sparingly reported from
      across the globe. The attempt to have cumulative information on prevalent
      nomenclature, definition, reminiscences, and clinical overtures has brought
      differential diagnosis and diagnosis in sharp focus, the highlights of which are
      outlined. Hence, it was considered important to review the evolution of treatment
      options available thus far including use of biologics.

PMID- 21950287
TI  - Folliculitis keloidalis nuchae is associated with the risk for bleeding from
      haircuts.
AB  - BACKGROUND: Folliculitis keloidalis nuchae (FKN), characterized by nucheal
      pimples and keloids, has a predilection for curly African hair. The disease is 10
      times more common in males than females. The aim of this study was to investigate
      determinants of FKN in males. METHODS: Factors associated with the presence of
      FKN were investigated from two cross-sectional studies involving 1042 children
      and 874 adults, respectively. All participants had given informed consent. A
      clinical diagnosis of FKN was made only if nucheal keloidal papules (or plaques)
      were present. Multiple logistic regression was used to assess the relationship
      between FKN and specific characteristics in male participants. RESULTS: The odds
      ratio (OR) for FKN in males was higher in the adult than the child study [OR =
      7.26, 95% confidence interval (CI) 3.13-16.88; P < 0.0001]. The OR in the group
      aged <25 years was similar to that in the group aged >50 years (OR = 2.44, 95% CI
      0.75-7.89; P = 0.14) but significantly higher in those aged >25-50 years (OR =
      5.75, 95% CI 2.67-12.64; P < 0.0001), which is inconsistent with inherent
      degenerative disease (in which the OR would be expected to increase or remain
      constant) and may correspond to the current popularity of closely shaven
      hairstyles. Most hair (86%) was cut close to the scalp with clippers, a process
      often accompanied by the exhibition of symptoms. For example, 47% of respondents
      reported transient haircut-related crusts or pimples (Yes vs. No, FKN OR = 3.44,
      95% CI 1.43-8.301; P = 0.006), and 32% of adult males reported at least one
      episode of bleeding (Yes vs. Never, FKN OR = 3.45, 95% CI 1.23-9.68; P < 0.019).
      CONCLUSIONS: Prospective studies are needed to clarify the extent to which
      mechanical haircut-associated injuries cause or are the result of FKN. Haircut
      associated bleeding raises concern about the potential transmission of blood
      borne infections.

PMID- 21950288
TI  - Anxiety and depression in patients with allergic and non-allergic cutaneous
      disorders.
AB  - BACKGROUND: Numerous studies have shown that anxiety and depression are more
      prevalent among patients suffering from chronic skin disorders. OBJECTIVES: The
      aims of this study were to assess the prevalences of depression and anxiety in
      patients suffering from chronic skin disorders, focusing particularly on allergic
      skin conditions. Additionally, we investigated resilience to disease progression
      using the Sense of Coherence Scale. METHODS: A total of 112 consecutive patients
      without known psychiatric disease were interviewed and asked to complete
      questionnaires in order to assess psychiatric symptomatology. The following
      scales were completed: the Mini International Neuropsychiatric Interview; the
      Hamilton Anxiety Scale (HAS); the Hamilton Depression Rating Scale (HDRS); and
      the self-administered questionnaire for the Sense of Coherence Scale (SoCS).
      RESULTS: Rates of anxiety and depression in patients with allergic and non
      allergic conditions were considerably higher than those in the general
      population. This difference was notable in patients with allergic skin diseases,
      reaching 58.3 and 48.3%, compared with 15.4 and 23.1% for participants with non
      allergic conditions, as measured by the HAS and HDRS, respectively (P < 0.05).
      Statistically significant negative correlations between scores on the SoCS and
      scores on the HAS (r = -0.45, P < 0.01) and HDRS (r = -0.37, P < 0.01) were
      observed. CONCLUSIONS: Our findings support the hypothesis that rates of anxiety
      and depression are higher among patients suffering from allergic chronic skin
      disorders. High SoCS scores may protect against the development of psychiatric
      illness in patients suffering from allergic skin disease.

PMID- 21950289
TI  - Hypomelanosis of Ito: pigmentary mosaicism with immature melanosome in
      keratinocytes.
AB  - BACKGROUND: Hypomelanosis of Ito is a rare genetic disorder characterized by
      whorled areas of hypomelanosis. The purpose of the present study was to revisit
      some aspects of Ito's hypomelanosis. METHODS: Clinical observations included
      ultraviolet-light-enhanced visualization (ULEV) method. Histochemistry,
      immunohistochemistry, and electron microscopy were performed on biopsy samples
      from the hypopigmented areas and the surrounding skin. RESULTS: Both the ULEV and
      microscopic examinations revealed the heterogeneity of the pigmentation.
      Hypomelanosis was characterized by a reduction in melanosomes, both in
      melanocytes and keratinocytes. These organelles were immature and atypical,
      showing a weak tyrosinase immunoreactivity. Melanosome macroautophagy was
      prominent in keratinocytes. Some clusters of the same cells exhibited strong
      immunoreactivity for the Mac 387 antibody (Ca(2+) -dependent calprotectin). Ulex
      europaeus agglutinin-1 (UEA-1) decorated the superficial layers of the epidermis.
      Such features are typically found in functionally altered keratinocytes. A number
      of dermal cells exhibited intense phagocytic activity linked to lysozyme
      immunoreactivity. CONCLUSIONS: Both the melanosome depletion and macroautophagy
      of immature melanosomes in keratinocytes appeared to represent prominent aspects
      of hypomelanosis of Ito. In sum, Ito's hypomelanosis combines structural and
      functional changes affecting both the melanocytes and keratinocytes in the skin.

PMID- 21950290
TI  - Adaptation of a Runyankore version of Skindex-16 for oral administration in
      Mbarara, Uganda.
AB  - BACKGROUND: Health-related quality of life instruments are typically developed
      and validated for use in developed countries by patients who can read and write.
      Little is known about the feasibility of using adaptations of validated
      instruments in situations where literacy rates are low. OBJECTIVE: We aimed to
      translate, culturally adapt, and test an oral version of Skindex-16 in
      Runyankore, the predominant language in Mbarara, Uganda, for use in dermatologic
      research. METHODS: Skindex-16 was forward- and back-translated to Runyankore. The
      Runyankore version was administered orally to 47 dermatology patients and 47
      random hospital visitors. Additional questions regarding duration,
      dyspigmentation, concealment status of the skin problem, and overall quality of
      life effect were also asked. RESULTS: Oral delivery was feasible; <= 10 minutes
      per subject. High Cronbach alpha values (0.86, 0.88, and 0.85 for symptoms,
      emotions, and functioning subscales, respectively) demonstrated internal
      consistency reliability. As hypothesized, subjects with reported skin problems,
      dyspigmentation, and difficulty in concealment had higher mean Skindex scores. A
      total of 72.4% of responses to the open-ended question were addressed in Skindex
      16, indicating content validity. CONCLUSION: The orally delivered Runyankore
      version of Skindex-16 is reliable, with construct and content validity, and
      feasible for use in dermatology research in Mbarara, Uganda. Orally administered
      quality of life instruments have potential for use in low literacy groups
      worldwide.

PMID- 21950291
TI  - Lipoatrophy in patients with AIDS: treatment with polymethylmethacrylate in
      Amazonas, Brazil.
AB  - BACKGROUND: The use of antiretroviral therapy (ART) in AIDS has been associated
      with lipodystrophic syndrome, which is characterized by metabolic alterations and
      abnormal corporal fat distribution. Our goal was to describe and evaluate the use
      of polymethylmethacrylate (PMMA) to treat lipoatrophy in patients with AIDS from
      Amazonas, Brazil. METHODS: Patients with AIDS undergoing ART and presenting with
      facial lipoatrophy were invited to participate in the study. A face-to-face
      interview was conducted, and patients were treated with applications of PMMA 30%.
      RESULTS: A total of 49 cases were included. The mean age was 45 (SD 6.1) years
      old, and the mean educational level (measured in schooling years) was 10.5 (SD
      3.2) years of schooling. The median of CD4 cell count was 482.5 (interquartile
      range: 338-574.5) cells/mm(3) . Stavudine and zidovudine were the most frequently
      prescribed ART drugs. The total number of PMMA injections ranged from one to five
      times, and side effects were not frequent. A total of 42 (85.7%) patients
      reported satisfaction after a follow-up of more than 12 months, presenting good
      fullness of the deformity. CONCLUSIONS: Our data showed that patients with AIDS
      with lipoatrophy related to ART could safely benefit from PMMA-based treatment.

PMID- 21950292
TI  - Keratosis circumscripta: a unique case and review of the literature.

PMID- 21950293
TI  - Knowledge, attitude, and performance of students toward skin cancer in Yazd,
      2009.
AB  - BACKGROUND: Cancer is increasingly recognized as a major and growing health
      concern in the Eastern Mediterranean Region (EMR), and skin cancers are the most
      prevalent cancers. The purpose of this study was to evaluate the knowledge,
      attitude, and performance of university students regarding skin cancer. METHODS:
      This cross-sectional study included 230 samples selected randomly from the
      students of Yazd universities. The reliability of the questionnaire was certified
      by specialists, validated by a pilot study, and confirmed by Alpha Cronbachs test
      (alpha = 0.8). SPSS software was used for data entry, manipulation, and analysis.
      RESULTS: The students studied had medium knowledge level related to skin cancer.
      Their attitude towards skin cancer was relatively good. The performance level of
      the population under study was moderate. Non-medical students had more poor
      knowledge, attitude, and performance than medical students. Overall results show
      a significant relationship between knowledge, attitude, and performance level of
      the population under study. CONCLUSION: Skin cancers are the most common form of
      cancers in our state, but my students do not have appropriate knowledge and
      performance levels about this disease. It is therefore proposed that related
      information should be given to them during continuous and regular educational
      programs.

PMID- 21950294
TI  - Invasive cutaneous Trichophyton shoenleinii infection in an immunosuppressed
      patient.

PMID- 21950295
TI  - Toxic epidermal necrolysis in the setting of systemic lupus erythematosus.

PMID- 21950296
TI  - Allergic and photoallergic conditions from unusual chlorpromazine exposure:
      report of three cases.

PMID- 21950297
TI  - Acute tuberculosis cutis miliaris disseminata in a patient with systemic lupus
      erythematosus.

PMID- 21950298
TI  - Acquired and familial mucinous nevus.

PMID- 21950299
TI  - Risk factors for basal cell carcinoma in a southern Brazilian population: a case
      control study.
AB  - BACKGROUND: Basal cell carcinoma (BCC) is the most common cancer to occur in
      Caucasian populations, and its incidence is increasing. Despite its frequency,
      there is a paucity of data on risk factors for BCC in some regions. OBJECTIVES:
      This study investigated the association between pigmentary characteristics,
      distinctive patterns of solar exposure, habits and lifestyle, and risk for BCC
      among patients attending a dermatology center in a region in southern Brazil.
      METHODS: We conducted a hospital-based, case-control study that included 127 case
      patients with histologically confirmed BCC and 280 cancer-free control subjects
      with other dermatologic conditions, observed between January 2006 and December
      2007. The study was conducted using a questionnaire and physical examination by a
      dermatologist. Relative risks were estimated using exposure odds ratios generated
      by cross-tabulation and logistic regression models. RESULTS: Risk for BCC was
      associated with family history of skin cancer, Fitzpatrick skin type I, and the
      presence of actinic keratoses, solar lentigines, leukoderma, and elastosis
      romboidalis nuchae. No effect was found for different patterns of solar exposure,
      eye, hair or skin color, exposure to non-solar ultraviolet radiation (UVR), or
      lifestyle-related habits such as sunscreen use and cigarette smoking.
      CONCLUSIONS: The results of this study suggest that skin type and family history
      of skin cancer may be important in establishing risk for developing BCC.
      Additionally, the detection by clinical examination of skin markers related to
      UVR action is important in establishing which patients are more likely to develop
      BCC.

PMID- 21950300
TI  - Weekly vs. daily administration of oral methotrexate (MTX) for generalized plaque
      psoriasis: a randomized controlled clinical trial.
AB  - Methotrexate (MTX) treatment for psoriasis is most often administered weekly,
      because the drug has been considered more hepatotoxic when taken daily. However,
      some patients may tolerate smaller, more frequent doses better. OBJECTIVE: To
      study the efficacy and toxicity of daily vs. weekly MTX. PATIENTS AND METHODS: In
      a randomized controlled trial, 101 patients with generalized plaque psoriasis
      received oral MTX 2.5 mg daily for weeks, 4 weeks and monthly for a total of 4
      months. Changes in PASI scores were classified into three categories: >75%
      improvement was considered significant; 25-75% moderate; and <25% poor. RESULTS:
      Sixty Group 1 patients and 81 Group 2 patients showed a significant response (P
      value 0.001); 19 patients in Group 1 and 14 in Group 2 responded moderately; 22
      patients in Group 1 and six patients from Group 2 responded poorly. Forty-five
      patients in Group 1 and 33 in Group 2 developed transient increases in liver
      enzymes (P-value 0.11). Nausea, headache, fatigue, and gastrointestinal upset
      were noted in four Group 1 patients and 30 Group 2 patients (P-value 0.0001).
      CONCLUSION: Nausea, vomiting, headache, and fatigue were significantly less
      common side effects in our patients who received MTX daily, but liver enzyme
      abnormalities were less common, and clinical efficacy was greater in the patients
      who received MTX weekly.

PMID- 21950301
TI  - Successful long-term treatment with the bradykinin B2 receptor antagonist
      icatibant in a patient with hereditary angioedema.
AB  - BACKGROUND: Hereditary angioedema (HAE) is a rare, autosomal dominant disorder
      caused by a C1-esterase inhibitor (C1-INH) deficiency (type 1) or qualitative
      defect (type 2). It is characterized by recurrent subcutaneous or submucosal
      edema attacks in various organs with a frequency from a few attacks to over one
      hundred attacks per year. METHODS: We report on the treatment of 141 attacks in a
      patient with hereditary angioedema with the bradykinin B2 receptor antagonist
      icatibant. RESULTS: During the entire observation period, efficacy of icatibant
      was maintained and not altered due to repeated administrations. No systemic or
      cardiovascular side affects were observed. CONCLUSIONS: In the present case,
      icatibant proved to be an effective and safe drug for the symptomatic treatment
      of acute HAE attacks. Its efficacy was not impaired by repeated administrations
      over a three-year period in this patient.

PMID- 21950302
TI  - Chump change: one dermatologist's experiences with market research surveys.

PMID- 21950303
TI  - Epithelioid cell histiocytoma and neurotized melanocytic nevus.

PMID- 21950308
TI  - Kinetics and mechanism of conformational changes in a G-quadruplex of thrombin
      binding aptamer induced by Pb2+.
AB  - It has been shown that guanine-rich DNA can fold into a G-quadruplex with certain
      metal cations. The spectral characteristics, thermostability, and kinetics for
      the formation of a Pb(2+)-driven G-quadruplex of thrombin-binding aptamer (TBA)
      were measured in the current work using a combination of ultraviolet (UV) and
      circular dichroism (CD) spectroscopy along with stopped-flow technique. CD
      spectra demonstrated that TBA could fold into a unique G-quadruplex with a strong
      positive peak at 312 nm. Analysis of the titration data reveals that the binding
      stoichiometry is 1:1 for the titration of TBA with Pb(NO(3))(2), which is in
      accordance with the localization of the Pb(2+) ion between the adjacent G
      quartets. Thermal denaturation profiles indicate that the Pb(2+)-induced
      intramolecular G-quadruplex is more stable than those driven by Na(+) or K(+)
      ions. Kinetic studies suggest that the Pb(2+)-induced folding G-quadruplex of TBA
      probably proceeds through the rapid formation of an intermediate Pb(2+)-TBA
      complex, which then isomerizes to the fully folded structure. Conformational
      changes transpire after the addition of Pb(NO(3))(2) to the Na(+)- or K(+)
      induced G-quadruplexes, which may be attributed to the replacement of Na(+) or
      K(+) ions by Pb(2+) ions and the generation of a more compact structure of the
      Pb(2+)-TBA structure. The relaxation time, tau, of folding the G-quadruplex is
      reduced from 1.05 s in the presence of Pb(2+) ions alone to 0.34 s under the
      cooperation of initially added Na(+) ions, while tau is increased to 8.33 s under
      the competition of initially added K(+) ions.

PMID- 21950309
TI  - Phenylsulfanylation of 3',4'-unsaturated adenosine employing thiophenol-N
      iodosuccinimide leads to 4'-phenylsulfanylcordycepin: synthesis of 4'-substituted
      cordycepins on the basis of substitution of the phenylsulfanyl leaving group.
AB  - Upon reaction of the 3',4'-unsaturated adenosine derivative 2 with N
      iodosuccinimide (NIS) and thiophenol, an unexpected electrophilic
      hydrophenylsulfanylation proceeded to provide 4'-phenylsulfanylcordycepin 7 in
      79% yield with the ratio 7a/7b = 6.6/1. A study of the reaction mechanism
      revealed that hydrogen iodide (HI) generated from NIS and PhSH acted as an active
      species. On the basis of a deuterium experiment using PhSD, initial protonation
      occurred at the beta face of the double bond to furnish the beta-pi complex III,
      which underwent anti addition of PhSH as a major pathway. Nucleophilic
      substitution of N(6)-pivaloylated 9 with various alcohols in the presence of N
      bromosuccinimide (NBS) gave the respective 4'-alpha-alkoxycordycepins 15a-21a as
      the major stereoisomers. Use of DAST in place of an alcohol gave the 4'-alpha
      fluoro analogue 23a stereoselectively. Radical-mediated carbon-carbon bond
      construction was also applicable to 7, giving 4'-alpha-allylcordycepin (24a) and
      4'-alpha-cyanoethylcordycepin (25) derivatives.

PMID- 21950310
TI  - Obesity increases initial rate of fibrin formation during blood coagulation in
      domestic shorthaired cats.
AB  - Obesity predisposes to a prothrombotic state in humans, but whether a similar
      state occurs in obese animals is unknown. The objective of the current study was
      to examine the effect of body fat percentage (BF) on haemostatic parameters
      including thromboelastography with tissue factor as activator (TF-TEG) in client
      owned indoor-confined physically inactive cats. Seventy-two cats were included
      following an initial thorough health examination, and a complete blood count,
      biochemistry panel, conventional coagulation panel and a TF-TEG analysis were
      performed with tissue factor (1:50,000) as activator. The cats were
      anaesthetized, and BF was measured using Dual-energy X-ray absorptiometry.
      Significant difference between lean (BF < 35%, n = 26), overweight (35% < BF <
      45%, n = 28) and obese (BF > 45%, n = 18) cats was identified using ANOVA. The
      correlation between BF, serum leptin and total adiponectin, respectively, with
      individual TEG and conventional coagulation parameters was evaluated. Obese cats
      showed a faster rate of fibrin formation (TF-TEG(R), p < 0.05), and TF-TEG(R) was
      positively correlated with plasma leptin levels. Increasing BF did not affect
      other conventional coagulation or TF-TEG parameters. In conclusion, this study
      indicates a connection between body fat content and altered haemostasis, also in
      cats. Whether feline obesity causes a hypercoagulable state of clinical relevance
      should be further investigated.

PMID- 21950311
TI  - Hybrid cyst on the sole.

PMID- 21950312
TI  - The safety and tolerability of spironolactone in patients with mild to moderate
      chronic kidney disease.
AB  - AIM: Mineralocorticoid receptor blockade (MRBs) in combination with angiotensin
      converting enzyme (ACE) inhibitors and angiotensin-II receptor blockade (ARBs)
      improve prognostic markers of cardiovascular and renal disease in early stage
      chronic kidney disease (CKD). Concerns relating to the safety and tolerability of
      MRBs in CKD may limit their use in a non clinical trial setting. METHODS In the
      Chronic Renal Impairment in Birmingham II study, 115 patients with non-diabetic
      early stage CKD (eGFR 30-89ml/min/1.73m(2) ) received 25mg daily of
      spironolactone for 4 weeks before randomization to continuing treatment or
      placebo for a further 36 weeks. All patients were on ACE inhibitors and/or ARB
      therapy. Potassium and renal function were checked at weeks 1, 2, 4, 8, 16, 28
      and 40. The incidence of hyperkalaemia, significant renal dysfunction (reduction
      eGFR >=25%) and adverse effects was assessed. RESULTS: After 40 weeks of
      treatment the incidence of serious hyperkalaemia (K(+) >=6.0mmol/L) was <1%. A
      potassium 5.5-5.9mmol/L occurred on >=1 occasion over follow-up in 11 patients
      (nine on spironolactone) and was predicted by baseline potassium >=5.0mmol/L and
      eGFR <=45 ml/min/1.73m(2) . Over follow-up, three patients experienced
      significant renal dysfunction but no patients withdrew due to intolerance or side
      effects. Changes in potassium, eGFR and systolic blood pressure were most
      apparent in the first 4 eeks. CONCLUSION: Spironolactone was well tolerated in
      selected patients with early stage CKD. Strict monitoring over the first month of
      treatment followed by standard surveillance as for ACE inhibitors and ARBs is
      suggested.

PMID- 21950313
TI  - Sibling and adult video modelling to teach a student with autism: imitation
      skills and intervention suitability.
AB  - PURPOSE: To investigate the effectiveness of adult-as-model and sibling-as-model
      video modelling procedures for an individual with autism who demonstrated limited
      imitation skills. METHODS: This study assessed the imitation ability of Matthew,
      a 15 year-old boy with autism, and then used video modelling, with his sibling
      and an adult as models, in order to teach him to match coins, respond to
      questions in a group discussion time and prepare a snack of noodles. RESULTS:
      Matthew seldom responded to imitative opportunities in the assessment. Also,
      minimal changes in his ability to perform the target behaviours resulted from
      either of the video modelling conditions. CONCLUSION: An individual's imitation
      skills are an important pre-requisite for successful video modelling
      intervention.

PMID- 21950314
TI  - Mxi2 sustains ERK1/2 phosphorylation in the nucleus by preventing ERK1/2 binding
      to phosphatases.
AB  - ERK1/2 (extracellular-signal-regulated kinase 1/2) MAPKs (mitogen-activated
      protein kinases) are tightly regulated by the cellular microenvironment in which
      they operate. Mxi2 is a p38alpha splice isoform capable of binding to ERK1/2 and
      ensuring their translocation to the nucleus. Therein Mxi2 sustains ERK1/2
      phosphorylation levels and, as a consequence, ERK1/2 nuclear signals are
      enhanced. However, the molecular mechanisms underlying this process are still
      unclear. In the present study, we show that Mxi2 prevents nuclear but not
      cytoplasmic phosphatases from binding to and dephosphorylating ERK1/2, disclosing
      an unprecedented mechanism for the spatial regulation of ERK1/2 activation. We
      also demonstrate that the kinetics of ERK1/2 extranuclear signals can be
      significantly altered by artificially tethering Mxi2 to the cytoplasm. In this
      case, Mxi2 abolishes ERK1/2 inactivation by cytoplasmic phosphatases and
      potentiates ERK1/2 functions at this compartment. These results highlight Mxi2 as
      a key spatial regulator of ERK1/2 functions, playing a pivotal role in the
      balance between ERK1/2 nuclear and cytoplasmic signals.

PMID- 21950315
TI  - Pyrazolylborates and their importance in tuning single-molecule magnet properties
      of {Fe(III)2Ni(II)} complexes.
AB  - A new tricyanoferrate(III) building block and a trinuclear single-molecule magnet
      derivative are described. The treatment of a 2:1 ratio of
      [NEt(4)][(Tp*(Bn))Fe(III)(CN)(3)].H(2)O.MeOH [1; Tp*(Bn) = tris(3,5-dimethyl-4
      benzyl)pyrazolylborate] with nickel(II) trifluoromethanesulfonate gives
      {[(Tp*(Bn))Fe(III)(CN)(3)](2)[Ni(II)(DMF)(4)]}.2DMF (2; DMF = N,N
      dimethylformamide). The symmetry-equivalent Fe(III)(LS) ions lead to a favorable
      alignment of anisotropy tensors (i.e., Fe...B axes) in 2, and an energy barrier
      of Delta(eff)/k(B) = 16.7 K is found for the S(T) = 2 complex.

PMID- 21950316
TI  - Molecular considerations for development of phage antibody libraries.
AB  - Nowadays, phage display libraries are used as robust tools for discovery and
      evolution of peptide/protein based drugs as well as targeting molecules, in
      particular monoclonal antibodies (mAbs) and its fragments (i.e., scFvs, Fabs, or
      bivalent F(ab')2). Phage display technology, as a molecular diversity approach,
      enables selection of antibody fragments (e.g., scFv/Fab) with high affinity,
      specificity and effector functions against various targets. However, such
      selection process itself is largely dependent upon various molecular factors such
      as methods for construction of phage library, phage/phagemid vectors, helper
      phage, host cells and biopanning processes. The current review article provides
      important molecular considerations for successful development of phage antibody
      libraries that may be used as a platform for translation of antibody fragments
      into viable diagnostic/therapeutic reagents.

PMID- 21950317
TI  - Is insulin resistance: the link between TG-rich lipoproteins and excess death?

PMID- 21950319
TI  - Power in group contexts: the influence of group status on promotion and
      prevention decision making.
AB  - This research examines how group status affects the impact of individual power
      positions on promotion versus prevention choices in group decision making. We
      consider that high power not only implies control, but also indicates
      responsibility for the achievement of group goals. We argue that the nature of
      these goals depends on the current status of the group. In Experiment 1,
      individuals who were accorded high power showed more promotion-oriented decisions
      in the low group status condition while decisions were more prevention oriented
      under high group status. Experiment 2 replicated these effects, and further
      demonstrated that they only emerge when those in power are explicitly made
      accountable for the achievement of group goals. These results are discussed in
      relation to regulatory focus theory, power theories, and the role of social
      identities and group goals in group dynamics.

PMID- 21950318
TI  - Myasthenogenicity of the main immunogenic region and endogenous muscle nicotinic
      acetylcholine receptors.
AB  - In myasthenia gravis (MG) and experimental autoimmune MG (EAMG), many
      pathologically significant autoantibodies are directed at the main immunogenic
      region (MIR), a conformation-dependent region at the extracellular tip of alpha1
      subunits of muscle nicotinic acetylcholine receptors (AChRs). Human muscle AChR
      alpha1 MIR sequences were integrated into Aplysia ACh-binding protein (AChBP).
      The chimera was potent in inducing both acute and chronic EAMG, though less
      potent than Torpedo electric organ AChR. Wild-type AChBP also induced EAMG but
      was less potent, and weakness developed slowly without an acute phase. AChBP is
      more closely related in sequence to neuronal alpha7 AChRs that are also
      homomeric; however, autoimmune responses were induced to muscle AChR, but not to
      neuronal AChR subtypes. The greater accessibility of muscle AChRs to antibodies,
      compared to neuronal AChRs, may allow muscle AChRs to induce self-sustaining
      autoimmune responses. The human alpha1 subunit MIR is a potent immunogen for
      producing pathologically significant autoantibodies. Additional epitopes in this
      region or other parts of the AChR extracellular domain contribute significantly
      to myasthenogenicity. We show that an AChR-related protein can induce EAMG. Thus,
      in principle, an AChR-related protein could induce MG. AChBP is a water-soluble
      protein resembling the extracellular domain of AChRs, yet rats that developed
      EAMG had autoantibodies to AChR cytoplasmic domains. We propose that an initial
      autoimmune response, directed at the MIR on the extracellular surface of muscle
      AChRs, leads to an autoimmune response sustained by muscle AChRs. Autoimmune
      stimulation sustained by endogenous muscle AChR may be a target for specific
      immunosuppression.

PMID- 21950320
TI  - G-estimation and artificial censoring: problems, challenges, and applications.
AB  - In principle, G-estimation is an attractive approach for dealing with confounding
      by variables affected by treatment. It has rarely been applied for estimation of
      the effects of treatment on failure-time outcomes. Part of this is due to
      artificial censoring, an analytic device which considers some subjects who
      actually were observed to fail as if they were censored. Artificial censoring
      leads to a lack of smoothness in the estimating function, which can pose problems
      in variance estimation and in optimization. It also can lead to failure to have
      solutions to the usual estimating functions, which then raises questions about
      the appropriate criteria for optimization. To improve performance of the
      optimization procedures, we consider approaches for reducing the amount of
      artificial censoring, propose the substitution of smooth for indicator functions,
      and propose the use of estimating functions scaled to a measure of the
      information in the data; we evaluate performance of these approaches using
      simulation. We also consider appropriate optimization criteria in the presence of
      information loss due to artificial censoring. We motivate and illustrate our
      approaches using observational data on the effect of erythropoietin on mortality
      among subjects on hemodialysis.

PMID- 21950321
TI  - Revisiting the peroxidase oxidation of 2,4,6-trihalophenols: ESR detection of
      radical intermediates.
AB  - The peroxidase oxidation of 2,4,6-trichlorophenol (TCP) has been clearly shown to
      result in 2,6-dichloro-1,4-benzoquinone (DCQ). DCQ is a 2-electron oxidation
      product of TCP that has undergone para dechlorination. Many peroxidases show
      similar oxidation of the substrate, TCP, to yield the quinone, DCQ. Depending on
      the substrate, peroxidases are thought to carry out both 1- and 2-electron
      oxidations; the mechanism can be confirmed by the detection of both enzyme and
      substrate intermediates. This article presents ESR evidence for the transient
      2,4,6-trichlorophenoxyl radical intermediate (TCP*), which exists free in
      solution, i.e., is not enzyme associated. These data are best explained as a 1
      electron peroxidase oxidation of TCP to form TCP*, followed by enzyme-independent
      radical reactions leading to the 2-electron oxidized product. Also presented are
      data for the peroxidase oxidation of 2,4,6-trifluorophenol and 2,6-dichloro-4
      fluorophenol.

PMID- 21950322
TI  - Selective and absolute quantification of endogenous hypochlorous acid with
      quantum-dot conjugated microbeads.
AB  - Endogenous hypochlorous acid (HOCl) secreted by leukocytes plays a critical role
      in both the immune defense of mammalians and the pathogenesis of various diseases
      intimately related to inflammation. We report the first selective and absolute
      quantification of endogenous HOCl produced by leukocytes in vitro and in vivo
      with a novel quantum dot-based sensor. An activated human neutrophil secreted 6.5
      +/- 0.9 * 10(8) HOCl molecules into its phagosome, and kinetic measurement for
      the secretions showed that the extracellular generation of HOCl was temporally
      retarded, but the quantity eventually attained a level comparable with its
      intraphagosomal counterpart with a delay of about 1.5 h. The quantity of HOCl
      secreted from the hepatic leukocytes of rats with or without stimulation of
      lipopolysaccharide was also determined. These results indicate a possibility to
      extend our approach to not only clinical settings for quantitative assessment of
      the bactericidal capability of isolated leukocytes of patients but also
      fundamental biomedical research that requires critical evaluation of the
      inflammatory response of animals.

PMID- 21950323
TI  - Themed section: molecular pharmacology of GPCRs.
AB  - As our knowledge and understanding of the way in which GPCRs operate continues to
      grow rapidly, many new opportunities are emerging to develop novel therapeutic
      agents. This themed issue of the British Journal of Pharmacology contains a
      series of papers that cover recent developments and identify approaches that may
      help determine future directions. Many of these papers contain material that was
      presented at the 6th International Molecular Pharmacology of G Protein-Coupled
      Receptors meeting held at the Monash Institute of Pharmaceutical Sciences in
      Melbourne Australia in late 2010.

PMID- 21950324
TI  - Pericardial monocusp reconstruction for pulmonary valve vegetation secondary to
      patent ductus arteriosus.
AB  - A case of pulmonary valve endocarditis in a patient with a ductus arteriosus
      (PDA) is reported. The PDA was ligated, the septal leaflet of the pulmonary valve
      was excised, and a pericardial monocusp reconstruction was performed.

PMID- 21950325
TI  - Tinea capitis outbreak in a paediatric refugee population, Tel Aviv, Israel.

PMID- 21950326
TI  - Temperature and length scale dependence of tetraalkylammonium ion solvation in
      water, formamide, and ethylene glycol.
AB  - This paper focuses on the temperature and length scale dependence of solvation of
      familiar hydrophobic solutes: tetraalkylammonium ions in highly associated
      solvents with H-bond networks. Standard enthalpies and heat capacities of
      solution of symmetrical tetraalkylammonium bromides in formamide (FA) and
      ethylene glycol (C(2)H(4)(OH)(2)) have been computed using experimental
      DeltaH(m)(sol) values and compared with previously reported enthalpies and heat
      capacities in pure water. Heat capacities of hydration are found to be large,
      positive, and increase almost linearly up to tetrapentylammonium bromide.
      Hydration of tetrahexyl- and tetraheptylammonium bromides is accompanied by much
      smaller heat capacity changes than would be expected from the length scale
      dependence observed. The same behavior reveals enthalpies and heat capacities of
      solute transfer from FA and C(2)H(4)(OH)(2) to water. The results obtained rather
      indicate that solvation of large tetraalkylammonium ions containing more than
      twenty carbon atoms is accompanied by much less water orientational ordering than
      for solutes of a moderate size. It results in smaller fluctuations in the water
      water pair energy in a hydration shell and consequently reduces the heat capacity
      of hydration. The comparison of tetraalkylammonium ion behavior in water and the
      nonaqueous solvents studied shows that the length scale dependence of solvophobic
      solvation is strongly pronounced in water but not in nonaqueous media.

PMID- 21950330
TI  - Mutation analysis of GJB3 and GJB4 in Chinese patients with erythrokeratodermia
      variabilis.

PMID- 21950331
TI  - Theory in plant science.

PMID- 21950332
TI  - Moving copper in plants.

PMID- 21950333
TI  - Ferns: a xylem success story.

PMID- 21950334
TI  - Past UV-B flux from fossil pollen: prospects for climate, environment and
      evolution.

PMID- 21950335
TI  - Bioenergy from trees.

PMID- 21950336
TI  - Fire regimes: moving from a fuzzy concept to geographic entity.

PMID- 21950337
TI  - A rare Y chromosome constitutional rearrangement: a partial AZFb deletion and
      duplication within chromosome Yp in an infertile man with severe
      oligoasthenoteratozoospermia.
AB  - We report a case of an infertile man with severe oligoasthenoteratozoospermia
      with a partial azoospermia factor b (AZFb) deletion and duplication region within
      chromosome Yp11.2. The hormonal profile was normal for serum concentrations of
      follicle-stimulating hormone, luteinizing hormone, testosterone and oestradiol.
      The patient, who showed a 46,XY karyotype, had an approximate 2.4 Mb inherited
      duplication region in Yp11.2 and a de novo partial AZFb deletion, which spanned
      5.25 Mb including eight protein coding genes and four non-coding transcripts, but
      did not remove the RBMY gene family. Both proximal and distal breakpoints of the
      deletion were outside any palindromic region or inverted repeat sequence and
      intra-chromosomal non-allelic homologous recombination could not have been the
      deletion mechanism. The partial AZFb deletion in our case diminished sperm
      production, but did not completely extinguish spermatogenesis. Considering severe
      oligozoospermia, spermatozoa in the patient's ejaculate were used for
      intracytoplasmic sperm injection, resulting in two twin pregnancies.

PMID- 21950339
TI  - Population regulation by habitat heterogeneity or individual adjustment?
AB  - 1. The habitat heterogeneity (HHH) and individual adjustment (IAH) hypotheses are
      commonly proposed to explain a decrease in reproduction rate with increasing
      population density. Higher numbers of low-quality territories with low
      reproductive success as density increases lead to a decrease in reproduction
      under the HHH, while more competition at high density decreases reproduction
      across all territories under the IAH. 2. We analyse the influence of density and
      habitat heterogeneity on reproductive success in eight populations of long-lived
      territorial birds of prey belonging to four species. Sufficient reliability in
      distinguishing between population-wide, site-specific and individual quality
      effects on reproduction was granted through the minimal duration of 20 years of
      all data sets and the ability to control for individual quality in five of them.
      3. Density increased in five populations but reproduction did not decrease in
      these. Territory occupancy as a surrogate of territory quality correlated
      positively with reproductive success but only significantly so in large data sets
      with more than 100 territories. 4. Reproductive success was always best explained
      by measures of territory quality in multivariate models. Direct or delayed (t-1)
      population density entered very few of the best models. Mixed models controlling
      for individual quality showed an increasing reproductive performance in older
      individuals and in those laying earlier, but measures of territory quality were
      also always retained in the best models. 5. We find strong support for the
      habitat heterogeneity hypothesis but weak support for the individual adjustment
      hypothesis. Both individual and site characteristics are crucial for reproductive
      performance in long-lived birds. Proportional occupancy of territories enables
      recognition of high-quality territories as preferential conservation targets.

PMID- 21950338
TI  - Artesunate/dihydroartemisinin pharmacokinetics in acute falciparum malaria in
      pregnancy: absorption, bioavailability, disposition and disease effects.
AB  - AIM: To determine if reported lower plasma concentrations of artemisinin
      derivatives for malaria in pregnancy result from reduced oral bioavailability,
      expanded volume of distribution or increased clearance. METHODS: In a
      sequentially assigned crossover treatment study, pregnant women with
      uncomplicated falciparum malaria received i.v. artesunate (i.v. ARS) (4mgkg(-1) )
      on the first day and oral ARS (4mgkg(-1) ) on the second, or, oral on the first
      and i.v. on the second, in both groups followed by oral ARS (4mgkg(-1) day(-1) )
      for 5 days. Plasma concentrations of ARS and dihyroartemisinin (DHA) were
      measured by liquid chromatography-mass-spectrometry on days 0, 1, 2 and 6.
      Controls were the same women restudied when healthy (3 months post partum).
      RESULTS: I.v. ARS administration resulted in similar ARS and DHA pharmacokinetics
      in pregnant women with malaria (n= 20) and in controls (n= 14). Oral
      administration resulted in higher total drug exposure in pregnancy [AUC (95% CI)
      in (ngml(-1) h)/(mgkg(-1) )] of 55.1 (30.1, 100.0) vs. 26.5 (12.2, 54.3) for ARS,
      P= 0.002 and 673 (386, 1130) vs. 523 (351, 724) for DHA, P= 0.007. The
      corresponding median absolute oral bioavailability (F%) was 21.7 (12.6, 75.1) vs.
      9.9 (6.0, 36.81) for ARS (P= 0.046) and 77.0 (42.2, 129) vs. 72.7 (42.0, 87.7)
      for DHA, P= 0.033. Total DHA exposure was lower at day 6 in pregnant women with
      malaria (P < 0.001) compared with day 0 or 1, but not in the controls (P= 0.084).
      CONCLUSIONS: This study demonstrates the effects of malaria on oral ARS drug
      disposition are greater than those of pregnancy. This probably results from a
      disease related reduction in first pass metabolism. The data are reassuring
      regarding current dosing recommendations.

PMID- 21950340
TI  - A learning assessment procedure as a test supplement for monitoring progress with
      two post-coma persons with a diagnosis of vegetative state.
AB  - OBJECTIVE: Evaluating a learning assessment procedure for monitoring progress
      with two post-coma adults with a diagnosis of vegetative state. METHOD: ABABCBCB
      and ABABCB designs were used for the two participants, with A representing
      baseline, B intervention and C control conditions. Participants' activation of an
      optic microswitch by eyelid closure produced stimulation during B phases.
      RESULTS: One participant increased responding during B phases and decreased it
      during the C condition, suggesting a non-reflective minimal level of
      consciousness. She showed P300 and mismatch negativity responses and scored at
      the vegetative level on the Coma Recovery Scale-Revised (CRS-R). The other
      participant increased responding during the initial B phases without decline
      during the first (viable) part of the C condition, suggesting a pre-conscious
      level. He showed indistinct P300 and mismatch negativity responses and vegetative
      level scores on the CRS-R. CONCLUSION: Learning data seemed reconcilable with
      neurophysiological measures and more positive than CRS-R scores.

PMID- 21950342
TI  - Granulomatous reaction at the site of healed herpes zoster in a patient with
      adult T-cell leukemia/lymphoma.

PMID- 21950341
TI  - Pharmacokinetics and distribution of minocycline in mature horses after oral
      administration of multiple doses and comparison with minimum inhibitory
      concentrations.
AB  - REASONS FOR PERFORMING STUDY: Minocycline holds great potential for use in horses
      not only for its antimicrobial effects but also for its anti-inflammatory and
      neuroprotective properties. However, there are no pharmacokinetic or safety data
      available regarding the use of oral minocycline in horses. OBJECTIVES: To
      determine pharmacokinetics, safety and penetration into plasma, synovial fluid,
      aqueous humour (AH) and cerebral spinal fluid (CSF) of minocycline after oral
      administration of multiple doses in horses and to determine the minimum
      inhibitory concentrations (MIC) of minocycline for equine pathogenic bacteria.
      METHODS: Six horses received minocycline (4 mg/kg bwt q. 12 h for 5 doses).
      Thirty-three blood and 9 synovial fluid samples were collected over 96 h. Aqueous
      humour and CSF samples were collected 1 h after the final dose. Minocycline
      concentrations were measured using high pressure liquid chromatography. The MIC
      values of minocycline for equine bacterial isolates were determined. RESULTS: At
      steady state, the mean +/- s.d. peak concentration of minocycline in the plasma
      was 0.67 +/- 0.26 ug/ml and the mean half-life was 11.48 +/- 3.23 h. The highest
      trough synovial fluid minocycline concentration was 0.33 +/- 0.12 ug/ml. The AH
      concentration of minocycline was 0.09 +/- 0.03 ug/ml in normal eyes and 0.11 +/-
      0.04 ug/ml in blood aqueous barrier-disrupted eyes. The mean CSF concentration of
      minocycline was 0.38 +/- 0.09 ug/ml. The MIC values were determined for 301
      isolates. Minocycline concentrations were above the MIC(50) and MIC(90) for many
      gram-positive equine pathogens. POTENTIAL RELEVANCE: This study supports the use
      of orally administered minocycline at a dose of 4 mg/kg bwt every 12 h for the
      treatment of nonocular infections caused by susceptible (MIC <= 0.25 ug/ml)
      organisms in horses. Further studies are required to determine the dose that
      would be effective for the treatment of ocular infections.

PMID- 21950344
TI  - Linear and cyclic tetrathiafulvalene-naphthalenediimide donor-acceptor molecules:
      metal ions-promoted electron transfer.
AB  - Three linear and one cyclic tetrathiafulvalene-1,4,5,8-naphthalenediimide (TTF
      NDI) compounds 1, 2, 3, and 4 were synthesized and studied in the presence of
      metal ions. Both absorption and electron spin resonance spectroscopic studies
      clearly indicate that electron transfer occurs from TTF to the NDI unit in the
      presence of metal ions (Pb(2+) and Sc(3+)) for linear compounds 1 and 2. The
      mechanism based on the metal ion coordination is proposed for the electron
      transfer within 1 and 2 after the addition of metal ions. Compound 3 exhibits
      intramolecular charge-transfer absorption because of the cyclophane framework.
      Interestingly, intramolecular electron transfer also takes place for 3 after the
      addition of either Sc(3+) or Pb(2+).

PMID- 21950343
TI  - Copine A is expressed in prestalk cells and regulates slug phototaxis and
      thermotaxis in developing Dictyostelium.
AB  - Copines are calcium-dependent membrane-binding proteins found in many eukaryotic
      organisms. We are studying the function of copines using the model organism,
      Dictyostelium discoideum. When under starvation conditions, Dictyostelium cells
      aggregate into mounds that become migrating slugs, which can move toward light
      and heat before culminating into a fruiting body. Previously, we showed that
      Dictyostelium cells lacking the copine A (cpnA) gene are not able to form
      fruiting bodies and instead arrest at the slug stage. In this study, we compared
      the slug behavior of cells lacking the cpnA gene to the slug behavior of wild
      type cells. The slugs formed by cpnA- cells were much larger than wild-type slugs
      and exhibited no phototaxis and negative thermotaxis in the same conditions that
      wild-type slugs exhibited positive phototaxis and thermotaxis. Mixing as little
      as 5% wild-type cells with cpnA- cells rescued the phototaxis and thermotaxis
      defects, suggesting that CpnA plays a specific role in the regulation of the
      production and/or release of a signaling molecule. Reducing extracellular levels
      of ammonia also partially rescued the phototaxis and thermotaxis defects of cpnA-
      slugs, suggesting that CpnA may have a specific role in regulating ammonia
      signaling. Expressing the lacZ gene under the cpnA promoter in wild-type cells
      indicated cpnA is preferentially expressed in the prestalk cells found in the
      anterior part of the slug, which include the cells at the tip of the slug that
      regulate phototaxis, thermotaxis, and the initiation of culmination into fruiting
      bodies. Our results suggest that CpnA plays a role in the regulation of the
      signaling pathways, including ammonia signaling, necessary for sensing and/or
      orienting toward light and heat in the prestalk cells of the Dictyostelium slug.

PMID- 21950345
TI  - Cystic fibrosis transmembrane conductance regulator protein expression rate in
      healthy spermatozoa is not correlated with ovum fertilisation rate.
AB  - Our previous studies have shown that the cystic fibrosis transmembrane
      conductance regulator (CFTR) was important for capacitation and fertilisation in
      mouse, guinea pig and human spermatozoa. However, it is unclear whether CFTR is
      correlated with ovum fertilisation rate. The present study was to test the
      possible relationship between spermatozoa CFTR protein expression rate in healthy
      men and ovum fertilisation rate during in vitro fertilisation. Ninety-four
      couples for female factor infertility for IVF-ET treatments were retrospectively
      studied. All the patients were divided into three groups based on the
      fertilisation rate of ovum in vitro. It was performed to explore whether there
      were differences in sperm CFTR protein expression rate among the three groups and
      the relevance between CFTR protein expression rate and ovum fertilisation rate.
      Our study showed that there was no significant differences in sperm CFTR protein
      expression rate among the three groups (F = 0.614, P = 0.544), and the relevance
      between spermatozoa CFTR protein expression rate and ovum fertilisation rate was
      not significantly different (r = 0.013, P = 0.904). These results further suggest
      that CFTR protein expression rate in healthy men spermatozoa was not associated
      with ovum fertilisation rate and thus we cannot predict ovum fertilisation
      results by sperm CFTR protein expression rate.

PMID- 21950347
TI  - Biochemical insight into physiological effects of H2S: reaction with
      peroxynitrite and formation of a new nitric oxide donor, sulfinyl nitrite.
AB  - The reaction of hydrogen sulfide (H2S) with peroxynitrite (a key mediator in
      numerous pathological states) was studied in vitro and in different cellular
      models. The results show that H2S can scavenge peroxynitrite with a corresponding
      second order rate constant of 3.3 +/- 0.4 * 103 M-1.s-1 at 23 degrees C (8 +/- 2
      * 103 M-1.s-1 at 37 degrees C). Activation parameters for the reaction (DeltaH?,
      DeltaS? and DeltaV?) revealed that the mechanism is rather associative than multi
      step free-radical as expected for other thiols. This is in agreement with a
      primary formation of a new reaction product characterized by spectral and
      computational studies as HSNO2 (thionitrate), predominantly present as sulfinyl
      nitrite, HS(O)NO. This is the first time a thionitrate has been shown to be
      generated under biologically relevant conditions. The potential of HS(O)NO to
      serve as a NO donor in a pH-dependent manner and its ability to release NO inside
      the cells has been demonstrated. Thus sulfide modulates the chemistry and
      biological effects of peroxynitrite by its scavenging and formation of a new
      chemical entity (HSNO2) with the potential to release NO, suppressing the pro
      apoptotic, oxidative and nitrative properties of peroxynitrite. Physiological
      concentrations of H2S abrogated peroxynitrite-induced cell damage as demonstrated
      by the: (i) inhibition of apoptosis and necrosis caused by peroxynitrite; (ii)
      prevention of protein nitration; and (iii) inhibition of PARP-1 [poly(ADP-ribose)
      polymerase 1] activation in cellular models, implying that a major part of the
      cytoprotective effects of hydrogen sulfide may be mediated by modulation of
      peroxynitrite chemistry, in particular under inflammatory conditions.

PMID- 21950348
TI  - Quantile regression for doubly censored data.
AB  - Double censoring often occurs in registry studies when left censoring is present
      in addition to right censoring. In this work, we propose a new analysis strategy
      for such doubly censored data by adopting a quantile regression model. We develop
      computationally simple estimation and inference procedures by appropriately using
      the embedded martingale structure. Asymptotic properties, including the uniform
      consistency and weak convergence, are established for the resulting estimators.
      Moreover, we propose conditional inference to address the special identifiability
      issues attached to the double censoring setting. We further show that the
      proposed method can be readily adapted to handle left truncation. Simulation
      studies demonstrate good finite-sample performance of the new inferential
      procedures. The practical utility of our method is illustrated by an analysis of
      the onset of the most commonly investigated respiratory infection, Pseudomonas
      aeruginosa, in children with cystic fibrosis through the use of the U.S. Cystic
      Fibrosis Registry.

PMID- 21950349
TI  - An update on ethnic differences in drug metabolism and toxicity from anti-cancer
      drugs.
AB  - INTRODUCTION: Based on recent emerging evidence of inter-ethnic differences in
      drug response and toxicity, ethnic diversity in pharmacokinetics,
      pharmacogenomics and clinical outcomes are being increasingly investigated.
      Ultimately, this will promote improved understanding of inter-individual
      differences in the pharmacokinetics and tolerance of cytotoxic drugs. AREAS
      COVERED: This article reviews potential explanations for the observed ethnic
      differences in treatment outcomes and provides clinical data to support this
      concept. A literature search was implemented on PubMed and PharmGKB to
      investigate the areas of ethnic differences in pharmacogenomics, pharmacogenetics
      and clinical outcomes of cancer therapies. EXPERT OPINION: There has been a
      relative paucity of clinical evidence linking genetic polymorphisms of genes
      encoding drug-metabolizing enzymes to the pharmacokinetics, pharmacodynamics and
      tolerance of anti-cancer drugs. Future research should focus on studies using
      large sample sizes, in the hope that they will provide results of high clinical
      significance. Due to the potential for ethnic differences to impact on both
      toxicities and benefits of systemic cancer therapies, the development of new
      therapeutic agents should include patients from diverse geographical ancestries
      in each phase of drug development.

PMID- 21950350
TI  - Expressions of dissatisfaction and complaint by people with learning
      disabilities: a discourse analytic study.
AB  - This paper uses critical discursive psychology to examine expressions of
      dissatisfaction and complaint by people with learning disabilities. UK government
      policies stress that people with learning disabilities should have more control
      over their lives. Expressing dissatisfaction about services is an important
      aspect of this process. However, given that such individuals are often treated as
      incompetent, and given the delicate nature of complaining about services one
      might rely on for day-to-day support, this can be difficult to do. In building
      complaints, speakers drew on repertoires about competence and incompetence, the
      right to free choice as a principle, and tempered dissatisfaction to make
      contrasts between good and bad supporters and practice. While the complaints show
      many of the general features of complaints identified in previous work in the
      general population, they were crafted to the particular institutional context of
      social care, and attended both explicitly and implicitly to the particular issues
      of competence, power, and authority found in those services. Speakers positioned
      themselves as competent, and service workers as more or less competent in their
      roles. Issues of power in social care services were observed explicitly in the
      accounts, whereby people described staff as controlling and it being difficult to
      voice dissatisfaction. They were also implicit in the way speakers drew on the
      others with institutional authority for corroboration and comparison.

PMID- 21950351
TI  - The management of patients on oral anticoagulation undergoing coronary stent
      implantation: a survey among interventional cardiologists from eight European
      countries.
AB  - PURPOSE: To evaluate the current management, and adherence to recommendations, of
      patients on oral anticoagulation (OAC) undergoing coronary stent implantation
      (PCI-S). METHODS: By means of a contact person who had been previously identified
      in 8 European countries, a questionnaire was electronically forwarded between
      April and July 2010 to the national institutions where PCI-S is performed.
      RESULTS: A total of 202 questionnaires (median response rate: 50%, range 33-78%)
      was received. The prevalence of OAC patients among those undergoing PCI-S is
      mostly reported 5-10% (97%). The peri-procedural pharmacological management
      mostly encompasses: preprocedural OAC interruption and bridging with low
      molecular-weight heparin (59%), intraprocedural administration of an
      unfractionated heparin bolus (81%), and use of glycoprotein IIb/IIIa inhibitors
      on an individual basis (79%). The radial approach is reported as the preferred
      option (58%), as well as the implantation of bare metal stents (76%). Triple
      therapy (warfarin, aspirin, clopidogrel) is the most frequently prescribed (80%),
      generally for 1 month after bare metal stent (77%) and for at least 12 months
      after drug-eluting stent (60%). Throughout triple therapy, the International
      Normalized Ratio is mostly targeted to the lower end of the therapeutic range
      (77%), and gastric protection is routinely prescribed (69%), mostly by giving
      proton-pump inhibitors (70%). CONCLUSIONS: Among the 202 interventional
      cardiologists from the 8 European countries interviewed, the management of
      patients on OAC undergoing PCI-S appears variable and only partially adherent to
      currently available recommendations.

PMID- 21950352
TI  - Heat capacities and asymmetric criticality of coexistence curves for benzonitrile
      + alkanes and dimethyl carbonate + alkanes.
AB  - The critical behavior of isobaric heat capacities per unit volume for a series of
      critical binary solutions {benzonitrile + octane, or dodecane, or hexadecane} and
      {dimethyl carbonate + nonane, or decane, or dodecane} were studied. The
      corresponding exponent was obtained to be in consistent with the 3D-Ising value.
      The amplitudes in one-phase and two-phase regions were deduced, which were used
      to test some critical amplitude ratios. Analysis of the dependence of the
      effective critical exponent of the heat capacity on the temperature indicated a
      critical crossover from the 3D-Ising to the mean-field for all the studied
      systems. It was found that the heat capacity does play an important role for
      describing the asymmetric criticality of coexistence curves by the complete
      scaling theory.

PMID- 21950353
TI  - Looking back: an occasion for celebration.

PMID- 21950354
TI  - D-Amino acid oxidase-mediated increase in spinal hydrogen peroxide is mainly
      responsible for formalin-induced tonic pain.
AB  - BACKGROUND AND PURPOSE: Spinal reactive oxygen species (ROS) are critically
      involved in chronic pain. D-Amino acid oxidase (DAAO) oxidizes D-amino acids such
      as D-serine to form the byproduct hydrogen peroxide without producing other ROS.
      DAAO inhibitors are specifically analgesic in tonic pain, neuropathic pain and
      cancer pain. This study examined the role of spinal hydrogen peroxide in pain and
      the mechanism of the analgesic effects of DAAO inhibitors. EXPERIMENTAL APPROACH:
      Formalin-induced pain behaviours and spinal hydrogen peroxide levels were
      measured in rodents. KEY RESULTS: Formalin injected into the paw increased spinal
      hydrogen peroxide synchronously with enhanced tonic pain; both were effectively
      prevented by i.t. fluorocitrate, a selective astrocyte metabolic inhibitor. Given
      systemically, the potent DAAO inhibitor CBIO (5-chloro-benzo[d]isoxazol-3-ol)
      blocked spinal DAAO enzymatic activity and specifically prevented formalin
      induced tonic pain in a dose-dependent manner. Although CBIO maximally inhibited
      tonic pain by 62%, it completely prevented the increase in spinal hydrogen
      peroxide. I.t. catalase, an enzyme specific for decomposition of hydrogen
      peroxide, completely depleted spinal hydrogen peroxide and prevented formalin
      induced tonic pain by 65%. Given systemically, the ROS scavenger PBN (phenyl-N
      tert-butylnitrone) also inhibited formalin-induced tonic pain and increase in
      spinal hydrogen peroxide. Formalin-induced tonic pain was potentiated by i.t.
      exogenous hydrogen peroxide. CBIO did not increase spinal D-serine level, and
      i.t. D-serine did not alter either formalin-induced tonic pain or CBIO's
      analgesic effect. CONCLUSIONS AND IMPLICATIONS: Spinal hydrogen peroxide is
      specifically and largely responsible for formalin-induced pain, and DAAO
      inhibitors produce analgesia by blocking spinal hydrogen peroxide production
      rather than interacting with spinal D-serine.

PMID- 21950360
TI  - Finasteride-related Leydig cell tumour: report of a case and literature review.
AB  - Leydig cell tumours (LCTs) of the testis are rare. Their origin is still unknown.
      This case report describes a potential relationship between LCT and prolonged
      exposure to Finasteride.

PMID- 21950359
TI  - Pregnancy under everolimus-based immunosuppression.
AB  - The ability to give birth to a live child is one of the best success of kidney
      transplantation. While there are an increasing number of pregnancies reported in
      kidney transplant recipients treated with cyclosporine or tacrolimus, there is
      little evidence of pregnancy among kidney transplant recipients exposed to
      sirolimus or everolimus. We present the first successful delivery in an organ
      transplant recipient exposed to everolimus during the whole gestation. The
      absence of congenital anomalies in the child as well as the recipient's
      successful renal outcome are promising, although pregnancy in renal transplant
      recipients exposed to everolimus should be considered at higher risk.

PMID- 21950361
TI  - A dimethyl ketal-protected benzoin-based linker suitable for photolytic release
      of unprotected peptides.
AB  - Photolabile 3',5'-dimethoxybenzoin-based linkers are advantageous for a variety
      of solid-phase synthetic procedures and manipulations of biomolecules because UV
      irradiation in aqueous media provides fast and essentially quantitative release
      of tethered molecules, while generating unreactive side products. Practical
      applications of previously reported linkers are compromised to some extent by the
      1,3-dithiane protection of the benzoin carbonyl group and the lengthy synthesis.
      We have extended the group of photocleavable 3',5'-dimethoxybenzoin-based linkers
      by designing and synthesizing a linker in which the carbonyl group is protected
      as a dimethyl ketal. This protection is compatible with commonly used
      esterification and amide bond formation techniques, including the Fmoc/tBu
      strategy for solid phase peptide synthesis, is stable under mild acidic
      conditions, and can be quantitatively removed in <5 min by 3% TFA in
      dichloromethane. Irradiation of beads carrying peptides attached to the linker at
      350 nm in aqueous or partially aqueous media affords >90% release after 30 min.
      The linker was synthesized from commercially available starting materials in five
      steps with an overall yield of 40% and without any column chromatography
      purification. Additionally, we developed a route to a dithiane-protected linker
      that requires only two steps and proceeds in 65% yield, a significant improvement
      over previous synthetic routes.

PMID- 21950362
TI  - Linking homelessness with mental illness.

PMID- 21950363
TI  - Nurses' perceptions of nursing interventions supporting quality of life in acute
      psychiatric wards.
AB  - PURPOSE: This study aimed to examine nurses' (N=29) perceptions of nursing
      interventions in supporting patients' quality of life (QoL) in acute psychiatric
      inpatient settings. DESIGN AND METHOD: An explorative descriptive study design
      was applied. The data were generated through seven focus group interviews and
      analyzed with qualitative content analysis. FINDINGS: Five main categories of
      nursing interventions to support patients' QoL were identified. Interventions
      were related to care planning, empowering interventions, social interventions,
      activating interventions, and security interventions. PRACTICE IMPLICATIONS:
      Emphasis should be placed on nurses' opportunities to improve patients' QoL
      according to patients' individual needs.

PMID- 21950364
TI  - The psychometric properties of the self-assessment of the Interpersonal
      Relationship Scale.
AB  - PURPOSE: The specific aims of this study were to establish the reliability and
      validity of the Self-Assessment of the Interpersonal Relationship Scale (SAIRS)
      and to ascertain whether the SAIRS measured the development of interpersonal
      competencies. DESIGN AND METHOD: This was an exploratory methodological study
      undertaken to analyze the psychometric properties of the SAIRS. The sample was
      composed of 248 subjects between the ages of 18 and 60. FINDINGS: The factor
      analysis yielded a one-factor solution that explained 33.3% of the variance with
      one component explaining 21% of the variance. Cronbach's alpha (0.92),
      demonstrated high internal consistency. PRACTICE IMPLICATIONS: SAIRS can provide
      nurses, supervisors, and educators with information regarding competency areas
      that need further instruction/practice to enhance the interpersonal relationship.

PMID- 21950365
TI  - His-story or her-story: deconstruction of the concepts of somatization towards a
      new approach in advanced nursing practice care.
AB  - PURPOSE: This article will endeavor to present an alternative view of somatoform
      disorders, assist in understanding the possible underlying comorbid psychiatric
      symptoms, and identify psychopharmacological options for treatment. CONCLUSIONS:
      Recognizing symptom clusters is a useful strategy when considering psychotropic
      options for treatment and management. PRACTICE IMPLICATIONS: The alternative
      strategies presented and discussed in this article can contribute to a useful and
      positive experience for both the clinician and the individual suffering from
      medically unexplained physical symptoms as they promote the care, health, and
      well-being of the individual rather than a cure, illness, and/or disease state
      that needs rendering, mending, and/or surgery.

PMID- 21950366
TI  - Wounding words: swearing and verbal aggression in an inpatient setting.
AB  - PURPOSE: The aim of the research was to investigate swearing and verbal
      aggression in Australian inpatient settings, including incidence, gender, patient
      motivation, and nursing interventions. DESIGN AND METHODS: A mixed methods
      approach utilizing the Overt Aggression Scale and a survey of 107 nurses'
      perceptions of their experience of swearing was used. FINDINGS: High levels of
      swearing and verbal aggression were found, with differing patterns for male and
      female patients. Nurses subjected to swearing experienced high levels of
      distress, especially females. All nurses appeared to use a limited range of
      interventions to deal with patient aggression. PRACTICAL IMPLICATIONS: In order
      to provide optimal care for patients, there is a clear need to improve nurses'
      ability to predict and prevent aggression.

PMID- 21950367
TI  - A case report for diagnosing anxiety in people with intellectual disability: the
      role of nurses in the application of a multidimensional diagnostic guideline.
AB  - PURPOSE: The purpose of this article is the presentation of a multidimensional
      guideline for the diagnosis of anxiety and anxiety-related behavior problems in
      people with intellectual disability (ID), with a substantial role for the nurse
      in this diagnostic process. DESIGN AND METHODS: The guideline is illustrated by a
      case report of a woman with ID with severe problems. FINDINGS: It appears that a
      multidimensional diagnostic approach involving multidisciplinary team efforts can
      result in a more accurate diagnosis and improved subsequent treatment. PRACTICE
      IMPLICATIONS: Nurses should be engaged in the diagnostic process because of their
      ability to make direct observations and to actively participate in carrying out
      all parts of the guideline.

PMID- 21950368
TI  - Prevalence and related factors of mood and anxiety disorders in a clinical sample
      of postmenopausal women.
AB  - PURPOSE: The purpose of the study was to investigate the prevalence and related
      factors of mood and anxiety disorders in postmenopausal women attending a
      gynecological outpatient clinic. METHODS: The study sample included 269
      postmenopausal women. The Structured Clinical Interview for the Diagnostic and
      Statistical Manual of Mental Disorders, 4th edition was performed to determine
      the disorders. RESULTS: Ninety-two (34.2%) women had at least one mood or anxiety
      disorder. The most common specific disorder was generalized anxiety disorder
      (15.6%). The existence of any mood or anxiety disorder was associated with poorer
      economic level. CONCLUSIONS: Mood and anxiety disorders were frequently observed
      in postmenopausal women who were admitted to a gynecology outpatient clinic.

PMID- 21950369
TI  - Biological perspectives: update on newer antipsychotic drugs: are they evidence
      based?

PMID- 21950370
TI  - Endocrine disruptors, the increase of autism spectrum disorder and its
      comorbidity with gender identity disorder--a hypothetical association.

PMID- 21950371
TI  - Pemphigoid gestationis with a complete hydatidiform mole.

PMID- 21950373
TI  - Behavioural trade-offs in response to external stimuli: time allocation of an
      Arctic ungulate during varying intensities of harassment by parasitic flies.
AB  - 1. Macroparasites may be a major factor shaping animal behaviour. Tundra
      ecosystems inhabited by caribou and reindeer (Rangifer tarandus) are known for
      large concentrations of ectoparasites including mosquitoes (Culicidae) and black
      flies (Simuliidae), as well as endoparasitic oestrid flies (Oestridae). 2.
      Increased intensity and duration of insect harassment because of climatic warming
      is hypothesized as a potential factor in recent declines of Rangifer across the
      circumpolar north. Although there is a well-observed relationship between insect
      harassment and caribou/reindeer behaviour, the influence of ecto- relative to
      endoparasitic species is unclear. Climatic changes may favour the activity
      patterns, distribution or abundance of certain insect species; thus,
      understanding differential effects on the behaviour of Rangifer is important. 3.
      We recorded caribou behaviour using group scan and focal sampling methods, while
      simultaneously trapping insects and recording weather conditions on the
      postcalving/summer range of the Bathurst barren-ground caribou herd in Northwest
      Territories and Nunavut, Canada, during 2007-2009. 4. We developed statistical
      model sets representing hypotheses about the effects of insects, weather,
      habitat/location, and date/time on caribou behaviour. We used multinomial
      logistic regression models to explore factors affecting the relative dominance of
      behaviour types within groups of caribou and fractional multinomial logistic
      regression models to determine factors influencing time allocation by individual
      caribou. We examined changes in feeding intensity using fractional logistic
      regression. 5. Relative dominance of insect avoidance behaviour within caribou
      groups and time allocation to insect avoidance by individual caribou increased
      when oestrid flies were present or black flies were active at moderate-high
      levels. Mosquito activity had relatively little effect on caribou behaviour. Time
      spent feeding was reduced by the greatest degree when all three insect types were
      present in combination. Feeding intensity was influenced to a greater extent by
      the accumulation of growing degree days over the course of the postcalving/summer
      season than by insect activity. Changes in Arctic systems that increase the
      activity/abundance of ecto- and endoparasites could have implications for the
      productivity of Rangifer populations.

PMID- 21950372
TI  - The analgesic effect of pregabalin in patients with chronic pain is reflected by
      changes in pharmaco-EEG spectral indices.
AB  - AIM: To identify electroencephalographic (EEG) biomarkers for the analgesic
      effect of pregabalin in patients with chronic visceral pain. METHODS: This was a
      double-blind, placebo-controlled study in 31 patients suffering from visceral
      pain due to chronic pancreatitis. Patients received increasing doses of
      pregabalin (75mg-300mg twice a day) or matching placebo during 3 weeks of
      treatment. Pain scores were documented in a diary based on a visual analogue
      scale. In addition, brief pain inventory-short form (BPI) and quality of life
      questionnaires were collected prior to and after the study period. Multi-channel
      resting EEG was recorded before treatment onset and at the end of the study.
      Changes in EEG spectral indices were extracted, and individual changes were
      classified by a support vector machine (SVM) to discriminate the pregabalin and
      placebo responses. Changes in individual spectral indices and pain scores were
      correlated. RESULTS: Pregabalin increased normalized intensity in low spectral
      indices, most prominent in the theta band (3.5-7.5Hz), difference of -3.18, 95%
      CI -3.57, -2.80; P= 0.03. No changes in spectral indices were seen for placebo.
      The maximum difference between pregabalin and placebo treated patients was seen
      in the parietal region, with a classification accuracy of 85.7% (P= 0.009).
      Individual changes in EEG indices were correlated with changes in pain diary (P=
      0.04) and BPI pain composite scores (P= 0.02). CONCLUSIONS: Changes in spectral
      indices caused by slowing of brain oscillations were identified as a biomarker
      for the central analgesic effect of pregabalin. The developed methodology may
      provide perspectives to assess individual responses to treatment in personalized
      medicine.

PMID- 21950374
TI  - Teaching students with autism to tie a shoelace knot using video prompting and
      backward chaining.
AB  - PURPOSE: To evaluate the effects of video prompting and backward chaining for
      teaching students with autism to tie a shoelace knot. METHOD: Videos featuring an
      adult and a peer or sibling model were used as part of the video prompting
      procedures to teach three boys with autism to tie a shoelace knot. A backward
      chaining procedure involving live modelling and verbal instruction was introduced
      following the video prompting phases. RESULTS: Although the video prompting
      interventions increased the number of steps in the shoelace tying task completed
      by each of the participants, the backward chaining procedure was more effective,
      enabling one participant to reach mastery and a second participant to approach
      mastery. CONCLUSION: Practitioners should consider the pre-requisite skills of
      the participants and the nature of the target behaviour when selecting an
      intervention to teach daily living skills to individuals with autism.

PMID- 21950376
TI  - Identification of a novel HLA-DRB1 allele through sequence-based typing of an
      Italian patient candidate for kidney transplant.
AB  - In this report, we describe the identification of the novel HLA-DRB1*13:120 that
      differs from the closest matching allele HLA-DRB1*13:65 at two nucleotidic
      position in the exon 2.

PMID- 21950375
TI  - Progress against cancer (1971-2011): how far have we come?
AB  - 'The big C', a common euphemism for cancer, has loomed large on the collective
      psyche of the mankind for centuries, not least because of the relative dearth of
      effective treatment against this disease but its ability to relentlessly evade
      them and come back to haunt us. However, the struggle against cancer took a
      decisive turn in 1971 when a relentless campaigning by health activists
      eventually led to signing of the National Cancer Act in the United States, an
      unprecedented event in the history of diseases. As we commemorate the 40th
      anniversary of the signing of that historic legislation, an assessment of the
      progress against cancer would naturally help us understand how we have fared so
      far in this struggle and guide us in our efforts to re-strategize and re-deploy
      our limited resources to their best use against this immortal enemy.

PMID- 21950377
TI  - Systems involving hydrogenated and fluorinated chains: volumetric properties of
      perfluoroalkanes and perfluoroalkylalkane surfactants.
AB  - As part of a combined experimental and theoretical study of the thermodynamic
      properties of perfluoroalkylalkanes (PFAAs), the liquid density of
      perfluorobutylpentane (F4H5), perfluorobutylhexane (F4H6), and
      perfluorobutyloctane (F4H8) was measured as a function of temperature from 278.15
      to 353.15 K and from atmospheric pressure to 70 MPa. The liquid densities of n
      perfluoropentane, n-perfluorohexane, n-perfluorooctane, and n-perfluorononane
      were also measured at room pressure over the same temperature range. The PVT
      behavior of the PFAAs was also studied using the SAFT-VR equation of state. The
      PFAA molecules were modeled as heterosegmented diblock chains, using different
      parameters for the alkyl and perfluoroalkyl segments, that were developed in
      earlier work. Through this simple approach, we are able to predict the
      thermodynamic behavior of the perfluoroalkylalkanes, without fitting to any
      experimental data for the systems being studied. Molecular dynamics simulations
      have also been performed and used to calculate the densities of the
      perfluoroalkylalkanes studied.

PMID- 21950378
TI  - A collagenase gel/physical defect model for controlled induction of superficial
      digital flexor tendonitis.
AB  - REASONS FOR PERFORMING STUDY: A consistent and clinically relevant model for the
      induction of core lesions confined to the mid-metacarpal superficial digital
      flexor tendon (SDFT) has not been previously reported. Injection of bacterial
      collagenase is commonly used but often results in large, irregular and
      inconsistent lesions that disrupt the superficial tendon layers and epitenon.
      OBJECTIVE: To develop and evaluate a new injection technique for collagenase
      induction of SDFT injury. METHODS: Collagenase gel was injected into a physical
      columnar defect created by longitudinally placing a curved 16 gauge 8.89 cm
      needle in the mid-metacarpal SDFT in a randomly selected forelimb of 10 horses. A
      placebo treatment injection was performed 1 week later. Serial ultrasound
      examinations were performed. Horses were subjected to euthanasia at 2 (n = 2), 4
      (n = 2), 8 (n = 4) and 16 (n = 2) weeks post treatment injection. Post mortem
      magnetic resonance imaging and histological analysis were performed. Gene
      expression (18S, SCX, TNC, TNMD, COL1A1, COL3A1, COMP, DCN, MMP1, MMP3 and
      MMP13), total DNA, glycosaminoglycan and collagen content were determined for
      experimental tendons (n = 10) and unaffected tendons (n = 9). RESULTS: Mid
      metacarpal SDFT core lesion induction was successful in all tendons with
      consistent lesion cross-sectional area and minimal epitenon disruption. Histology
      confirmed loss of normal tendon architecture after tendonitis induction and
      subsequent healing of the tendon core lesion. Compared with gene expression in
      unaffected tendons, several tested genes were significantly upregulated (COL1A1,
      COL3A1, TNMD, SCX, TNC, MMP13), while others showed significant downregulation
      (COMP, DCN, and MMP3). CONCLUSION: Compared with the previously used direct
      injection of collagenase, this injection technique was easily performed and
      induced more consistent lesions that were mid-metacarpal and did not disrupt the
      epitenon. POTENTIAL RELEVANCE: This model will allow for objective assessment of
      therapies for tendon regeneration in the mid-metacarpal SDFT prior to clinical
      trials and routine clinical application.

PMID- 21950379
TI  - Scedosporium apiospermum skin infection mimicking tuberous xanthoma.

PMID- 21950381
TI  - Direct liquid chromatography method for the simultaneous quantification of
      hydroxytyrosol and tyrosol in red wines.
AB  - A validated HPLC method with fluorescence detection for the simultaneous
      quantification of hydroxytyrosol and tyrosol in red wines is described. Detection
      conditions for both compounds were optimized (excitation at 279 and 278 and
      emission at 631 and 598 nm for hydroxytyrosol and tyrosol, respectively). The
      validation of the analytical method was based on selectivity, linearity,
      robustness, detection and quantification limits, repeatability, and recovery. The
      detection and quantification limits in red wines were set at 0.023 and 0.076 mg
      L(-1) for hydroxytyrosol and at 0.007 and 0.024 mg L(-1) for tyrosol
      determination, respectively. Precision values, both within-day and between-day (n
      = 5), remained below 3% for both compounds. In addition, a fractional factorial
      experimental design was developed to analyze the influence of six different
      conditions on analysis. The final optimized HPLC-fluorescence method allowed the
      analysis of 30 nonpretreated Spanish red wines to evaluate their hydroxytyrosol
      and tyrosol contents.

PMID- 21950382
TI  - Effect of age on the pharmacokinetics of fimasartan (BR-A-657).
AB  - OBJECTIVES: The aim of this study was to compare the pharmacokinetics (PK) and
      safety of fimasartan (BR-A-657), an angiotensin II receptor antagonist, between
      healthy young (19 - 45 years) and older (>= 65 years) male subjects. METHODS: To
      assess the effect of age on PK and safety, fimasartan was administered as a
      single 240 mg tablet to 12 young and 10 older male subjects, followed by serial
      blood sampling over 48 h. Plasma concentrations of fimasartan were analyzed using
      validated HPLC-MS/MS. Clinical and laboratory adverse events were assessed.
      RESULTS: After oral administration of 240 mg fimasartan, the mean area under the
      plasma concentration-time curve from time zero to infinity (AUC(0->infinity)) was
      2899.0 ng/ml/h in the older, which was significantly greater than in young
      subjects (1767.4 ng/ml/h; p = 0.03). The geometric mean AUC(0->infinity) was
      69.4% higher in older than in young subjects. The maximum plasma concentration
      (C(max)), time to reach C(max) and elimination half-life for fimasartan did not
      differ significantly between the older and young groups. Importantly, fimasartan
      was well tolerated during this study. CONCLUSIONS: While some PK parameters were
      statistically different between the two groups, the effect of age on the PK was
      modest (e.g., AUC increase < twofold in older subjects).

PMID- 21950380
TI  - Structural anatomy of telomere OB proteins.
AB  - Telomere DNA-binding proteins protect the ends of chromosomes in eukaryotes. A
      subset of these proteins are constructed with one or more OB folds and bind with
      G+T-rich single-stranded DNA found at the extreme termini. The resulting DNA-OB
      protein complex interacts with other telomere components to coordinate critical
      telomere functions of DNA protection and DNA synthesis. While the first crystal
      and NMR structures readily explained protection of telomere ends, the picture of
      how single-stranded DNA becomes available to serve as primer and template for
      synthesis of new telomere DNA is only recently coming into focus. New structures
      of telomere OB fold proteins alongside insights from genetic and biochemical
      experiments have made significant contributions towards understanding how protein
      binding OB proteins collaborate with DNA-binding OB proteins to recruit
      telomerase and DNA polymerase for telomere homeostasis. This review surveys
      telomere OB protein structures alongside highly comparable structures derived
      from replication protein A (RPA) components, with the goal of providing a
      molecular context for understanding telomere OB protein evolution and mechanism
      of action in protection and synthesis of telomere DNA.

PMID- 21950383
TI  - Identification of partially linear structure in additive models with an
      application to gene expression prediction from sequences.
AB  - The additive model is a semiparametric class of models that has become extremely
      popular because it is more flexible than the linear model and can be fitted to
      high-dimensional data when fully nonparametric models become infeasible. We
      consider the problem of simultaneous variable selection and parametric component
      identification using spline approximation aided by two smoothly clipped absolute
      deviation (SCAD) penalties. The advantage of our approach is that one can
      automatically choose between additive models, partially linear additive models
      and linear models, in a single estimation step. Simulation studies are used to
      illustrate our method, and we also present its applications to motif regression.

PMID- 21950384
TI  - Impact of intervention: can we affect typical and atypical development of the
      human brain?

PMID- 21950385
TI  - Can cerebral palsy impairments be minimized in infants at risk? Potential
      insights from basic neuroscience research.

PMID- 21950386
TI  - Brain plasticity and recovery from early cortical injury.
AB  - Neocortical development represents more than a simple unfolding of a genetic
      blueprint: rather, it represents a complex dance of genetic and environmental
      events that interact to adapt the brain to fit a particular environmental
      context. Most cortical regions are sensitive to a wide range of experiential
      factors during development and later in life, but the injured cortex appears to
      be unusually sensitive to perinatal experiences. This paper reviews the factors
      that influence how normal and injured brains (both focal and ischemic injuries)
      develop and adapt into adulthood. Such factors include prenatal experiences in
      utero as well as postnatal experiences throughout life. Examples include the
      effects of sensory and motor stimulation, psychoactive drugs (including illicit
      and prescription drugs), maternal and postnatal stress, neurotrophic factors, and
      pre- and postnatal diet. All these factors influence cerebral development and
      influence recovery from brain injury during development.

PMID- 21950387
TI  - Harnessing activity-dependent plasticity to repair the damaged corticospinal
      tract in an animal model of cerebral palsy.
AB  - The corticospinal tract (CST) is the principal motor control pathway for skilled
      movements. It has a protracted postnatal development, creating a protracted
      period of vulnerability to perinatal brain and spinal cord injury. Research has
      shown that the motor signs in cerebral palsy (CP) reflect the loss of CST
      connections as well as development of abnormal motor systems connections,
      especially between the developing CST and spinal motor circuits. In this paper,
      we discuss a feline model of CP that we have developed. The animals develop a
      pattern of abnormal CST connections that is remarkably similar to that seen in
      hemiplegic CP and visuomotor impairments. Using this model we devised neural
      activity-based therapeutic approaches to repair the abnormal CST connections and
      restore normal skilled movement control. Our studies stress that more active CST
      connections are better able to maintain strong synaptic connections with spinal
      motor circuits. We propose that perinatal trauma initiates a vicious cycle in
      which CST axons that are spared after an injury are at a disadvantage for
      maintaining spinal connections, leading to further reductions in connections and
      motor signs. If this is so, targeted activation of the spared CST might interrupt
      this process and lead to functional improvement.

PMID- 21950388
TI  - The experience-dependent maturation of prefronto-limbic circuits and the origin
      of developmental psychopathology: implications for the pathogenesis and therapy
      of behavioural disorders.
AB  - The maturation of prefronto-limbic neuronal pathways that mediate essential
      affective and social regulatory functions is experience dependent. Immediately
      after birth the infant's affective experiences, especially those embedded in the
      relationship with the primary caregiver, trigger the reorganization and adaptive
      fine-tuning of synaptic circuits. Research in humans and in animal models
      supports the hypothesis that socio-emotional deprivation and emotional trauma
      during early childhood may leave 'scars' in prefronto-limbic function, brain
      regions that are essential for emotional behaviour, learning, and memory. The
      focus of this review is to point out that mechanisms involved in structuring and
      optimizing neural circuits during brain development might also be used in
      moulding personality and behaviour during psychotherapy in the adult brain.

PMID- 21950389
TI  - Developmental programming of early brain and behaviour development and mental
      health: a conceptual framework.
AB  - The Developmental Origins of Health and Disease (DOHaD) hypothesis studies the
      short- and long-term consequences of the conditions of the developmental
      environment for phenotypic variations in health and disease. Central to this
      hypothesis is the idea of interdependence of developmental influences, genes, and
      environment. Developmental programming effects are mediated by alterations in
      fundamental life functions, and the most enduring effects seem to occur if the
      main regulatory instances of the organ - the (epi)genome and the brain - are
      affected. Some new insights in the role of chromatin, in cellular development and
      differentiation, and neural plasticity from the field of epigenetics are
      introduced, followed by a section on epigenetics and brain development. It is
      proposed to extend the DOHaD hypothesis into the 'Developmental Origins of
      Behaviour, Health, and Disease' (DOBHaD) concept. Pregnancy and the early
      postnatal period are times of both great opportunity and considerable risk, and
      their influence can extend over a lifetime. The DOBHaD hypothesis opens
      fundamental new perspectives on preventing diseases and disorders.

PMID- 21950390
TI  - Prevention of neurodevelopmental sequelae of jaundice in the newborn.
AB  - Although its cause, jaundice in the newborn, is extremely common, the disabling
      neurological disorder kernicterus is very rare. Kernicterus may be prevented by
      selecting those infants who are at risk of extreme jaundice or who may be
      particularly vulnerable to bilirubin neurotoxicity. Because the tools for
      achieving that goal are inadequate, a secondary strategy is needed. This involves
      a plan for emergency treatment of severely jaundiced infants, in particular those
      who present with neurological symptoms. In this paper I review the strategies for
      preventing extreme jaundice, and for reversing neurotoxicity in those infants for
      whom the principal strategies fail. Briefly, the tools for prevention include
      measurement of bilirubin while the infant is staying in the maternity unit,
      plotting the value on an hour-specific chart, assessing other risk factors for
      jaundice, and educating the parents. Emergency treatment should include
      immediate, high-irradiance phototherapy, consideration of intravenous immune
      globulin, and preparation for an exchange transfusion.

PMID- 21950391
TI  - Ultrasound detection of white matter injury in very preterm neonates: practical
      implications.
AB  - AIM: Diffuse white matter injury is not well detected by cranial ultrasonography
      (CUS). The aim of this study was twofold: (1) to assess in very preterm neonates
      the predictive values of individual CUS abnormalities for white matter injury on
      MRI and neurological outcome; (2) to develop a strategy optimizing CUS detection
      of white matter injury. METHOD: Very preterm neonates (n=67; 44 males, 23
      females) underwent serial CUS and single MRI. Predictive values of CUS findings
      for a white matter classification on MRI, individual MRI findings, and
      neurological outcome at 2 years corrected age were calculated. The effects of
      timing and frequency of CUS were evaluated. RESULTS: Periventricular
      echodensities (PVEs) predicted abnormal white matter on MRI, but absence of PVEs
      did not predict absence of white matter changes. Peri- and intraventricular
      haemorrhage (P/IVH) was highly predictive of abnormal white matter on MRI.
      Frequency and timing of CUS did not influence predictive values. P/IVH and
      abnormal ventricular size/shape were reasonably predictive of unfavourable
      outcome, whereas absence of CUS abnormalities predicted a favorable outcome.
      INTERPRETATION: (1) If PVEs are present, there is a significant chance of
      abnormal white matter on MRI. (2) Increasing frequency of CUS does not increase
      its diagnostic performance for white matter injury. (3) P/IVH is highly
      predictive of abnormal white matter on MRI and reasonably predictive of
      unfavourable outcome. (4) Absence of PVEs and P/IVH on CUS does not guarantee
      normal white matter, but predicts a favourable outcome.

PMID- 21950392
TI  - Neurodevelopmental outcome in preterm infants.
AB  - AIM: To determine the distribution of cognitive and motor scores in preterm
      children, and to establish the influence of brain lesions and decreasing
      gestational age thereon. METHOD: One hundred and six very preterm children (63
      males, 43 females; gestational age 24.0-31.6 wk; birthweight 480-2275 g) were
      assessed for cognition and motor outcome at 6 to 12 years. We assessed total,
      verbal, and performance IQ using the Wechsler Intelligence Scale for Children,
      and motor outcome using the Movement Assessment Battery for Children (Movement
      ABC). RESULTS: The IQs and Movement ABC z-scores were normally distributed, but
      shifted to the left. Mean total IQ (SD) was 91 (12), performance IQ 89 (13), and
      verbal IQ 93 (15), being 0.60, 0.73, and 0.47 SD lower than the norm
      respectively. Movement ABC z-scores were -1.27 SD lower (SD 1.01). IQ and
      Movement ABC z-scores did not correlate with brain lesions or gestational age.
      INTERPRETATION: The distribution curve for cognition and motor outcome at school
      age is shifted to the left in preterm children, with an effect size of 0.60 SD
      for IQ (nine IQ points) and 1.27 SD for motor outcome. These findings are
      restricted to the current group. Developmental disruptions, affecting cerebral
      white matter, cortex, cerebellum, and thalamus might be involved, although the
      exact pathogenetic mechanism is unclear.

PMID- 21950393
TI  - Infant Motor Profile and cerebral palsy: promising associations.
AB  - AIM: The Infant Motor Profile (IMP) is a novel qualitative assessment of motor
      behaviour in infancy. The aim of this study was to determine whether IMP scores
      throughout infancy differ between children with and without cerebral palsy (CP)
      at 18 months. Furthermore, we evaluated the predictive ability of IMP scores
      throughout infancy for CP. METHOD: Fifty-nine preterm (median gestational age
      29.7 wk, median birthweight 1285 g) and 30 term infants (median gestational age
      40.1 wk, median birthweight 3588 g) were included. IMP assessments were
      longitudinally performed at (corrected) ages of 4, 6, 10, and 12 months.
      Neurological outcome was determined at 18 months with the neurological
      examination according to Hempel. We compared total and domain IMP scores
      throughout infancy between infants with and without CP. RESULTS: In the term
      group none of the children was diagnosed with CP at the age of 18 months, in the
      preterm group eight had CP at 18 months (14%). Three had unilateral spastic CP,
      and five bilateral spastic CP. Children with CP (n=8) at 18 months had lower IMP
      scores throughout infancy than children without. These differences were most
      pronounced for the domains variation and performance. The predictive ability of
      the total IMP scores throughout infancy for CP was high (area under receiver
      operating characteristic curve 0.89-0.99) and most pronounced for the variation
      and performance domains. INTERPRETATION: IMP scores throughout infancy and CP at
      18 months are strongly related. In particular, low scores on the variation and
      performance domains were important indicators for CP. To determine the exact
      predictive ability of the IMP, further research is needed.

PMID- 21950394
TI  - The effects of preterm infant massage on brain electrical activity.
AB  - AIM: Early intervention programmes based on the manipulation of the extra-uterine
      environment have been used in preterm infants with the aim of improving
      development and functional outcome. Infant massage, among them, has proved
      effective for weight gain and reduced length of stay in the neonatal intensive
      care unit. We have recently shown that infant massage accelerates brain
      maturation of low-risk preterm infants without brain abnormalities as measured by
      global parameters of electroencephalography (EEG) activity. In the present study
      we further analyse the same cohort of preterm infants, testing the hypothesis
      that massage determines changes in EEG spectral activity, a highly sensitive
      index of brain maturation. METHOD: Infants were randomly allocated to a massage
      or comparison group. Intervention consisted of standard care only (comparison
      group) or standard care plus infant massage (massage group). Massage was started
      at around 10 days after birth and was provided for 12 days during a 2-week
      period. EEG was performed at around 1 and 4 weeks, i.e. before and after
      intervention. Spectral EEG analysis was performed on 80 seconds of active sleep,
      applying the fast Fourier transform on the signal obtained from eight monopolar
      derivations. RESULTS: The modification in global EEG spectral power between the
      two assessments was significantly different for the two groups, especially for
      the delta band activity; the spectral power did not change in massaged infants
      although, not surprisingly, it decreased significantly in the comparison group,
      as shown by previous studies. INTERPRETATION: We propose that massage
      intervention affects the maturation of brain electrical activity and favours a
      process more similar to that observed in utero in term infants.

PMID- 21950395
TI  - Challenges and limitations in early intervention.
AB  - Research over the past three decades has shown that early intervention in infants
      biologically at risk of developmental disorders, irrespective of the presence of
      a brain lesion, is associated with improved cognitive development in early
      childhood without affecting motor development. However, at present it is unknown
      whether early intervention is also able to improve developmental outcome in
      infants with a serious lesion of the brain. This paper discusses factors that
      might play a role in the effect of early intervention. The following picture
      emerged from the limited evidence available: (1) coaching of parents seems an
      effective means of intervention; (2) our understanding of the plasticity of the
      developing human brain is currently too limited to allow a direct practical
      implementation in early intervention; (3) intervention before term age should
      primarily focus on stress reduction, intervention after term age on stimulation
      of infant development; and (4) our knowledge of the best ways to stimulate infant
      development is scant. Nevertheless, preliminary data suggest that offering the
      infant ample opportunities to explore by self-produced motor activities the
      borders of their own abilities might be a good strategy for promoting
      developmental outcome, including functional mobility.

PMID- 21950396
TI  - To constrain or not to constrain, and other stories of intensive upper extremity
      training for children with unilateral cerebral palsy.
AB  - Impaired hand function is among the most functionally disabling symptoms of
      unilateral cerebral palsy. Evidence-based treatment approaches are generally
      lacking. However, recent approaches providing intensive upper extremity training
      appear promising. In this review, we first describe two such approaches,
      constraint-induced movement therapy (CIMT) and bimanual training (hand-arm
      bimanual intensive therapy). We then summarize findings across more than 100
      participants in our CIMT/bimanual training studies since 1997. We show that (1)
      at high intensities, CIMT and bimanual training improve dexterity and bimanual
      upper extremity use; (2) bimanual training may allow direct practice of
      functionally meaningful goals, and such practice may transfer to unpracticed
      goals and improve bimanual coordination; (3) 90 hours of CIMT and bimanual
      training leads to greater improvements than 60 hours of the same treatments; (4)
      higher doses may be required for bimanual training; (5) increased dosing
      frequency and shaping may be needed for older children; and (6) combined
      CIMT/bimanual approaches may be useful, but require sufficient intensity.
      Together these findings suggest that dosage (treatment amount and frequency),
      more so than ingredients, may well be the key to successful training protocols,
      especially for older children. Such rehabilitation efforts should be 'child
      friendly', and as least invasive as possible, especially because these approaches
      may be provided throughout development.

PMID- 21950397
TI  - The role of the family in intervention of infants at high risk of cerebral palsy:
      a systematic analysis.
AB  - During the past two decades, awareness of the role of the family in the child's
      life has increased and the term 'family-centred services' (FCS) has been
      introduced to facilitate care for children with special needs and their families.
      It is, however, unclear how various early intervention programmes incorporate
      family involvement in service delivery. The present study systematically analyses
      the nature of family involvement in six frequently used early intervention
      programmes for infants at high risk of developmental disorders:
      neurodevelopmental treatment, treatment according to Vojta, Conductive Education,
      Infant Health and Development Program, Infant Behaviour Assessment and
      Intervention Program, and Coping with and Caring for infants with special needs -
      a family-centred programme (COPCA). The analysis shows that the role of the
      family is diverse: it varies from parent training to be a therapist without
      attention to family function (in Vojta) to the autonomous family that receives
      coaching (COPCA). The data suggest two trends over time: (1) from child-focused
      to family-focused orientation; and (2) from professionally directed guidance to
      coaching based on equal partnership.

PMID- 21950398
TI  - Family and quality of life: key elements in intervention in children with
      cerebral palsy.
AB  - Modern thinking about children's health, as embodied in the framework of the
      World Health Organization's International Classification of Functioning,
      Disability and Health - Child and Youth Version, requires that we be attentive to
      the 'context' of children's lives, namely their families and the well-being of
      their families. Family-centred services provide both a guide to the 'processes'
      of service by service providers and measurable evidence-based outcomes that link
      better 'processes' with better parental 'outcomes'. This brief paper provides an
      overview of these topics, arguing that the themes we address in services, and the
      way we do that, can have important effects on families, and by extension, on
      their children.

PMID- 21950399
TI  - Relationship between contractions of the uterus and concentration of PGF2alpha in
      uterine venous blood after luteolysis in gilts.
AB  - The origin and physiological significance of high pulses of prostaglandin F2alpha
      (PGF2alpha) in uterine venous blood that occur 2-3 days after luteolysis are not
      well understood. We studied the relationship between contractions of the uterus
      evoked by exogenous oxytocin (OT) and PGF2alpha concentration in uterine venous
      blood on day 17 of the porcine oestrous cycle. The infusion of OT into the
      uterine artery produced an immediate increase in the uterine intraluminal
      pressure (UIP) (p < 0.001) and a simultaneous elevation in PGF2alpha
      concentration in uterine venous blood (p < 0.0001). The infusion of indomethacin
      (IND) into the uterine artery slightly decreased PGF2alpha concentration in
      uterine venous blood, but it did not suppress uterine contraction or the rapid
      increase in PGF2alpha concentration in uterine venous blood just after OT
      infusion (p < 0.0001), which was lower that in gilts not treated with IND. We
      conclude that the spikes of PGF2alpha concentration in uterine venous blood
      occurring after OT infusion on day 17 of the porcine oestrous cycle are mainly
      caused by the excretion with venous blood from the remodelled uterus and that
      PGF2alpha synthesis may contribute to this. These results suggest that the high
      spikes in PGF2alpha concentration that occur 2-3 days after luteolysis in pigs,
      sheep, cows and mares all have a similar origin.

PMID- 21950401
TI  - Pyrosequencing survey of the microbial diversity of 'narezushi', an archetype of
      modern Japanese sushi.
AB  - AIMS: This study aimed to analyse microbiota of the fermented food 'narezushi',
      an archetype of modern Japanese sushi. The pyrosequencing technique was used to
      analyse sequences of 16S ribosomal DNA contained in six narezushi products.
      METHODS AND RESULTS: The V1-V2 regions of the 16S ribosomal DNA were amplified
      from different narezushi products using PCR, and approximately 120,000 sequences
      were phylogenetically assigned at the genus level, using the Ribosomal Database
      Project classifier. In all samples, the microbial populations consisted of more
      than 90% Lactobacillales, mainly Lactobacillus or Pediococcus, reflecting their
      crucial role in narezushi fermentation. There were more than 700 operational
      taxonomy units in all samples, with Shannon-Wiener index varying from 1.69 to
      2.60. CONCLUSIONS: The microbiota of all narezushi products were shown to consist
      largely of Lactobacillales populations. Interestingly, different species were
      found to be dominant in each product. SIGNIFICANCE AND IMPACT OF THE STUDY: This
      study provides an insight into the bacterial composition of fermented fish-based
      foods, which are consumed worldwide. Significant differences in the dominant
      species were observed between products, possibly because of the starter-free
      production process.

PMID- 21950400
TI  - Sulphide quinone reductase contributes to hydrogen sulphide metabolism in murine
      peripheral tissues but not in the CNS.
AB  - BACKGROUND AND PURPOSE: Hydrogen sulphide (H(2) S) is gaining acceptance as a
      gaseous signal molecule. However, mechanisms regarding signal termination are not
      understood. We used stigmatellin and antimycin A, inhibitors of sulphide quinone
      reductase (SQR), to test the hypothesis that the catabolism of H(2) S involves
      SQR. EXPERIMENTAL APPROACH: H(2) S production and consumption were determined in
      living and intact mouse brain, liver and colonic muscularis externa using gas
      chromatography and HPLC. Expressions of SQR, ethylmalonic encephalopathy 1
      (Ethe1) and thiosulphate transferase (TST; rhodanese) were determined by RT-PCR
      and immunohistochemistry. KEY RESULTS: In the colonic muscularis externa, H(2)
      (35) S was catabolized to [(35) S]-thiosulphate and [(35) S]-sulphate, and
      stigmatellin reduced both the consumption of H(2) (35) S and formation of [(35)
      S]-thiosulphate. Stigmatellin also enhanced H(2) S release by the colonic
      muscularis externa. In the brain, catabolism of H(2) (35) S to [(35) S]
      thiosulphate and [(35) S]-sulphate, which was stigmatellin-insensitive, partially
      accounted for H(2) (35) S consumption, while the remainder was captured as
      unidentified (35) S that was probably bound to proteins. Levels of mRNA encoding
      SQR were higher in the colonic muscularis externa and the liver than in the
      brain. CONCLUSIONS AND IMPLICATIONS: These data support the concept that
      termination of endogenous H(2) S signalling in the colonic muscularis externa
      occurs via catabolism to thiosulphate and sulphate partially via a mechanism
      involving SQR. In the brain, it appears that H(2) S signal termination occurs
      partially through protein sequestration and partially through catabolism not
      involving SQR. As H(2) S has beneficial effects in animal models of human
      disease, we suggest that selective inhibition of SQR is an attractive target for
      pharmaceutical development.

PMID- 21950402
TI  - Self-reported discrimination and discriminatory behaviour: the role of attachment
      security.
AB  - Past research shows that attachment security is linked to low prejudice (Hofstra,
      Van Oudenhoven & Bunnk, 2005; Mikulincer & Shaver, 2001). We extend this research
      by examining the role of attachment security in discriminatory choices and
      discriminatory behaviour. The current study examines the influence of primed
      attachment security (vs. neutral prime) on self-reported discrimination and
      actual discriminatory behaviour towards Muslims. Results illustrate that primed
      attachment security (vs. a neutral prime) significantly predicts both the choice
      to discriminate against Muslims and subsequent behavioural discrimination towards
      a Muslim. Implications for increasing attachment security as a means of reducing
      prejudice and discrimination are discussed.

PMID- 21950406
TI  - Periprandial administration of inhaled iloprost: a risk factor for digestive
      bleeding?

PMID- 21950407
TI  - Evaluating the effects of trophic complexity on a keystone predator by
      disassembling a partial intraguild predation food web.
AB  - 1. Many taxa can be found in food webs that differ in trophic complexity, but it
      is unclear how trophic complexity affects the performance of particular taxa. In
      pond food webs, larvae of the salamander Ambystoma opacum occupy the intermediate
      predator trophic position in a partial intraguild predation (IGP) food web and
      can function as keystone predators. Larval A. opacum are also found in simpler
      food webs lacking either top predators or shared prey. 2. We conducted an
      experiment where a partial IGP food web was simplified, and we measured the
      growth and survival of larval A. opacum in each set of food webs. Partial IGP
      food webs that had either a low abundance or high abundance of total prey were
      also simplified by independently removing top predators and/or shared prey. 3.
      Removing top predators always increased A. opacum survival, but removal of shared
      prey had no effect on A. opacum survival, regardless of total prey abundance. 4.
      Surprisingly, food web simplification had no effect on the growth of A. opacum
      when present in food webs with a low abundance of prey but had important effects
      on A. opacum growth in food webs with a high abundance of prey. Simplifying a
      partial IGP food web with a high abundance of prey reduced A. opacum growth when
      either top predators or shared prey were removed from the food web and the loss
      of top predators and shared prey influenced A. opacum growth in a non-additive
      fashion. 5. The non-additive response in A. opacum growth appears to be the
      result of supplemental prey availability augmenting the beneficial effects of top
      predators. Top predators had a beneficial effect on A. opacum populations by
      reducing the abundance of A. opacum present and thereby reducing the intensity of
      intraspecific competition. 6. Our study indicates that the effects of food web
      simplification on the performance of A. opacum are complex and depend on both how
      a partial IGP food web is simplified and how abundant prey are in the food web.
      These findings are important because they demonstrate how trophic complexity can
      create variation in the performance of intermediate predators that play important
      roles in temporary pond food webs.

PMID- 21950408
TI  - Male accessory gland infection frequency in infertile patients with chronic
      microbial prostatitis and irritable bowel syndrome.
AB  - Recently, we reported an increased prevalence of chronic bacterial prostatitis
      (CBP) in patients with prostatitis syndromes (PS) and irritable bowel syndrome
      (IBS) compared with patients with PS alone. The aim of this study was to evaluate
      the frequency of male accessory gland infections (MAGI) in patients with CBP plus
      IBS and to compare the sperm parameters of patients with or without MAGI. Fifty
      consecutive patients with the following criteria were enrolled: (i) infertility;
      (ii) diagnosis of CBP; and (iii) diagnosis of IBS according to the Rome III
      criteria. The following two aged-matched control groups were also studied:
      infertile patients with CBP alone (n = 56) and fertile men (n = 30) who fathered
      a child within the previous 3 months. Patients and controls underwent to an
      accurate anamnesis, administration of the NIH-Chronic Prostatitis Symptom Index
      (NIH-CPSI) and the Rome III questionnaires for prostatitis and IBS, respectively,
      physical examination, and semen analysis. A significantly higher frequency of
      MAGI was found in patients with CBP plus IBS (82.0%) compared with the patients
      with CBP alone (53.6%) or the fertile men (0%). The presence of MAGI in the
      patients with CBP plus IBS was associated with a significantly lower sperm
      concentration, total number, and forward motility, and with a higher seminal
      leucocyte concentration compared with the patients with CBP alone and MAGI. Sperm
      normal morphology was similar in the groups of patients. All sperm parameters did
      not differ significantly in both the groups of patients without MAGI. The
      patients with CBP plus IBS had a significantly higher frequency of MAGI compared
      with the patients with CBP alone. This was associated with worse sperm parameters
      and, hence, poorer reproductive prognosis. We suggest to search for the presence
      of IBS in the patients with PS and in particular when CBP and/or worse sperm
      parameters are present.

PMID- 21950409
TI  - Gold(III)-catalyzed tandem conjugate addition/annulation of 4-hydroxycoumarins
      with alpha,beta-unsaturated ketones.
AB  - An efficient and selective approach for the synthesis of functionalized
      pyranocoumarins has been developed via a gold(III)-catalyzed tandem conjugate
      addition/annulation reaction of 4-hydroxycoumarins with alpha,beta-unsaturated
      ketones.

PMID- 21950410
TI  - Circumscribed palmar or plantar hypokeratosis: two cases and a review of
      published work.

PMID- 21950411
TI  - Less is more.

PMID- 21950412
TI  - An epidemic of plagiarism: original text is best but when is copying copying?

PMID- 21950413
TI  - Detrimental effect of fluid resuscitation in the initial management of severely
      ill children in Africa.

PMID- 21950414
TI  - Use of salivary osmolality to assess dehydration.
AB  - OBJECTIVE: To investigate the ability of salivary osmolality to assess
      dehydration while subjects perform alternating work/rest cycles in personal
      protective equipment (PPE). METHODS: Eight healthy men (mean +/- standard
      deviation age: 23.5 +/- 4.9 years; body fat: 17.8% +/- 5.0%; maximum volume of
      oxygen consumption [VO(2max)]: 57.2 +/- 5.5 mL.kg(-1).min(-1)) performed two
      exercise trials: one while wearing shorts and a T-shirt (EX) and one while
      wearing firefighting PPE (EX+PPE). Saliva samples were taken before exercise, at
      minutes 40, 80, and 120 of the exercise trial, and during recovery. RESULTS:
      Percent body mass loss (BML) was significantly greater while the subjects were
      wearing PPE (2.18% +/- 0.54% vs. control 0.81% +/- 0.30%). Salivary osmolality
      increased significantly in both trials (73.4 +/- 12.4 to 125.1 +/- 30.3 mOsm.kg(
      1) and 70.1 +/- 12.5 to 83.6 +/- 17.7 mOsm.kg(-1)); however, the increase in the
      EX+PPE trial was significantly greater than the increase in the EX trial. Plasma
      osmolality did not change significantly in either trial, whereas urinary
      osmolality increased significantly in both trials. Changes in salivary osmolality
      were strongly correlated with percent BML (r = 0.80; p < 0.01). CONCLUSION:
      Salivary osmolality may be a sensitive indicator of moderate dehydration under
      carefully controlled conditions.

PMID- 21950415
TI  - Topological principles of borosilicate glass chemistry.
AB  - Borosilicate glasses display a rich complexity of chemical behavior depending on
      the details of their composition and thermal history. Noted for their high
      chemical durability and thermal shock resistance, borosilicate glasses have found
      a variety of important uses from common household and laboratory glassware to
      high-tech applications such as liquid crystal displays. In this paper, we
      investigate the topological principles of borosilicate glass chemistry covering
      the extremes from pure borate to pure silicate end members. Based on NMR
      measurements, we present a two-state statistical mechanical model of boron
      speciation in which addition of network modifiers leads to a competition between
      the formation of nonbridging oxygen and the conversion of boron from trigonal to
      tetrahedral configuration. Using this model, we derive a detailed topological
      representation of alkali-alkaline earth-borosilicate glasses that enables the
      accurate prediction of properties such as glass transition temperature, liquid
      fragility, and hardness. The modeling approach enables an understanding of the
      microscopic mechanisms governing macroscopic properties. The implications of the
      glass topology are discussed in terms of both the temperature and thermal history
      dependence of the atomic bond constraints and the influence on relaxation
      behavior. We also observe a nonlinear evolution of the jump in isobaric heat
      capacity at the glass transition when substituting SiO(2) for B(2)O(3), which can
      be accurately predicted using a combined topological and thermodynamic modeling
      approach.

PMID- 21950416
TI  - Evaluation of donor semen quality provided by six sperm banks: a retrospective
      study of 1877 artificial insemination cycles.
AB  - This study aimed at evaluating the impacts of sperm quality of six national sperm
      banks on pregnancy rates (PRs) of artificial insemination with donor sperm (AID)
      in China. A large retrospective analysis was performed on 1877 insemination
      cycles in 1209 women in a unique setting during a 3.5-year period. Global PRs of
      22.1% per cycle and 34.2% per patient were achieved. The PRs of the six banks
      varied from 15.5% to 29.0% (P = 0.011). Significant differences were observed in
      the quality of donor semen provided by the six sperm banks. Moreover, in some
      banks, the poor sperm quality was related to the suboptimal PRs. However, in
      certain banks, high values of sperm parameters did not result in satisfactory PRs
      accordingly. These data demonstrated that variability of donor semen quality
      existed in the different banks. But, sperm parameters after thawing may not be
      detrimental factors affecting the success rate of AID treatment. Further studies
      are needed to seek potential molecular markers for predicting fertility potency
      of donor sperm.

PMID- 21950417
TI  - Optimal photosensitizers for photodynamic therapy of infections should kill
      bacteria but spare neutrophils.
AB  - Photodynamic therapy (PDT) for localized microbial infections exerts its
      therapeutic effect both by direct bacterial killing and also by the bactericidal
      effects of host neutrophils stimulated by PDT. Therefore, PDT-induced damage to
      neutrophils must be minimized, while direct photoinactivation of bacteria is
      maintained to maximize the therapeutic efficacy of antimicrobial PDT in vivo.
      However, there has been no study in which the cytocidal effect of PDT on
      neutrophils was investigated. In this study, the cytocidal effects of PDT on
      neutrophils were evaluated using different antimicrobial photosensitizers to find
      suitable candidate photosensitizers for antimicrobial PDT. PDT on murine
      peripheral-blood neutrophils was performed in vitro using each photosensitizer at
      a concentration that exerted a maximum bactericidal effect on methicillin
      resistant Staphylococcus aureus, and morphological alteration and viability of
      neutrophils were studied. Most neutrophils were viable (>80%) after PDT using
      toluidine blue-O (TB) or methylene blue (MB), while neutrophils showed
      morphological change and their viabilities were decreased (<70%) after PDT using
      other photosensitizers (erythrosine B, rose bengal, crystal violet, Photofrin,
      new methylene blue and Laserphyrin). These results suggest that PDT using TB or
      MB can preserve host neutrophils while exerting a significant therapeutic effect
      on in vivo localized microbial infection.

PMID- 21950418
TI  - The effects of an advanced uterine environment on embryonic survival in the mare.
AB  - REASONS FOR PERFORMING THE STUDY: During embryo transfer (ET) the equine embryo
      can tolerate a wide degree of negative asynchrony but positive asynchrony of >2
      days usually results in embryonic death. There is still confusion over whether
      this is due to the inability of the embryo to induce luteostasis or to an
      inappropriate uterine environment. OBJECTIVES: To assess embryo survival and
      development in an advanced uterine environment. HYPOTHESIS: Embryo-uterine
      asynchrony, not the embryo's inability to induce luteostasis, is responsible for
      embryonic death in recipient mares with a >2 days chronologically advanced
      uterus. METHODS: Experiment 1: Thirteen Day 7 embryos were transferred to the
      uteri of recipient mares with luteal prolongation, occasioned by manual crushing
      of their own conceptus, such that donor-recipient asynchrony was between +13 and
      +49 days. Experiment 2: Day 7 embryos were transferred to recipient mares
      carrying their own conceptus at Days 18 (n = 2), 15 (n = 2), 14 (n = 4), 12 (n =
      4) or 11 (n = 4) of gestation. In addition, Day 8 embryos were transferred to 4
      pregnant recipient mares on Day 11 of gestation. RESULTS: No pregnancies resulted
      following transfer of Day 7 embryos to recipients in prolonged dioestrus with
      asynchronies between +13 and +49 days. However, the use of early pregnant mares
      as recipients resulted in 5/20 (25%) twin pregnancies, 4 of which came from the
      transfer of a Day 8 embryo to a Day 11 recipient. All transferred embryos showed
      retarded growth, with death occurring in 4/5 (80%). CONCLUSIONS AND POTENTIAL
      RELEVANCE: The results emphasise the importance of an appropriate uterine
      environment for embryo growth and the inability of equine embryos to survive
      transfer to a uterus >2 days advanced even when luteostasis is achieved. It is
      possible that in normal, non-ET equine pregnancy, embryo-uterine asynchrony may
      account for some cases of embryonic death.

PMID- 21950419
TI  - Influence of carbohydrates on the interaction of procyanidin B3 with trypsin.
AB  - The biological properties of procyanidins, in particular their inhibition of
      digestive enzymes, have received much attention in the past few years. Dietary
      carbohydrates are an environmental factor that is known to affect the interaction
      of procyanidins with proteins. This work aimed at understanding the effect of
      ionic food carbohydrates (polygalacturonic acid, arabic gum, pectin, and xanthan
      gum) on the interaction between procyanidins and trypsin. Physical-chemical
      techniques such as saturation transfer difference-NMR (STD-NMR) spectroscopy,
      fluorescence quenching, and nephelometry were used to evaluate the interaction
      process. Using STD-NMR, it was possible to identify the binding of procyanidin B3
      to trypsin. The tested carbohydrates prevented the association of procyanidin B3
      and trypsin by a competition mechanism in which the ionic character of
      carbohydrates and their ability to encapsulate procyanidins seem crucial leading
      to a reduction in STD signal and light scattering and to a recovery of the
      proteins intrinsic fluorescence. On the basis of these results, it was possible
      to grade the carbohydrates in their aggregation inhibition ability: XG > PA > AG
      ? PC. These effects may be relevant since the coingestion of procyanidins and
      ionic carbohydrates are frequent and furthermore since these might negatively
      affect the antinutritional properties ascribed to procyanidins in the past.

PMID- 21950420
TI  - Pharmacological treatment of generalized anxiety disorder.
AB  - INTRODUCTION: Generalized anxiety disorder (GAD) is a chronic, relapsing,
      debilitating disorder, associated with markedly impaired social and occupational
      functioning. Pharmacological treatment is considered standard care and several
      drug classes are now FDA approved for the treatment of GAD. While there are clear
      data for the efficacy of short-term acute treatment, long-term treatment and
      treatment-resistant GAD remain challenging. AREAS COVERED: This article describes
      current pharmacological treatment options for GAD, with focus on benzodiazepines,
      azapirones, antidepressants and anticonvulsant and antipsychotic drugs. Recent
      findings from placebo-controlled clinical trials are reviewed and evidence-based
      clinical implications are discussed. A PubMed search was completed using the
      terms: 'generalized anxiety disorder AND treatment' and 'generalized anxiety
      disorder AND therapy'. Additional pivotal trials were included for a historical
      perspective (older landmark trials that established efficacy and safety for older
      drug classes in the treatment of GAD). EXPERT OPINION: Efficacy for treatment of
      GAD has been established for several different drug classes. At present, based on
      clear efficacy and good tolerability, first-line treatment with either a
      selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine
      reuptake inhibitor (SNRI) is indicated. If an initial, at least moderate,
      clinical response is achieved under antidepressant therapy, treatment should be
      at least continued for 12 months.

PMID- 21950421
TI  - Effect of low-concentration chlorine dioxide gas against bacteria and viruses on
      a glass surface in wet environments.
AB  - AIMS: To evaluate the efficacy of low-concentration chlorine dioxide (ClO(2)) gas
      against model microbes in the wet state on a glass surface. METHODS AND RESULTS:
      We set up a test room (39 m(3)) and the ClO(2) gas was produced by a ClO(2) gas
      generator that continuously releases a constant low-concentration ClO(2) gas.
      Influenza A virus (Flu-A), feline calicivirus (FCV), Staphylococcus aureus and
      Escherichia coli were chosen as the model microbes. The low-concentration ClO(2)
      gas (mean 0.05 ppmv, 0.14 mg m(-3)) inactivated Flu-A and E. coli (>5 log(10)
      reductions) and FCV and S. aureus (>2 log(10) reductions) in the wet state on
      glass dishes within 5 h. CONCLUSIONS: The treatment of wet environments in the
      presence of human activity such as kitchens and bathrooms with the low
      concentration ClO(2) gas would be useful for reducing the risk of infection by
      bacteria and viruses residing on the environmental hard surfaces without adverse
      effects. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates that the
      low-concentration ClO(2) gas (mean 0.05 ppmv) inactivates various kinds of
      microbes such as Gram-positive and Gram-negative bacteria, enveloped and
      nonenveloped viruses in the wet state.

PMID- 21950422
TI  - Lipocalin-2 is associated with modulation of disease phenotype in a patient with
      concurrent JAK2-V617F and BCR-ABL mutation.
AB  - We investigated the role of lipocalin-2 (LCN-2) and its receptor (SLC22A17) in
      mediating clonal dominance in a patient with both BCR-ABL and JAK2-V617F
      mutations. LCN-2 mRNA showed a near 50-fold increase in expression, accompanied
      by down-regulation of SLC22A17, coinciding with increase in BCR-ABL transcripts,
      loss of JAK2-V617F and change of clinical phenotype from polycythaemia vera to
      chronic myeloid leukaemia. These changes were reversed after commencing imatinib
      mesylate. Consistent with experimental studies, BCR-ABL+ cells express LCN-2
      leading to suppression of BCR-ABL- cells and explain their eventual dominance
      when occurring together with JAK2-V617F.

PMID- 21950423
TI  - The robot is in.

PMID- 21950427
TI  - Medical robotics a hot technology comes to life.

PMID- 21950428
TI  - Five steps to achieving HIPAA compliance.

PMID- 21950430
TI  - Making the right hires and helping them succeed.

PMID- 21950431
TI  - Spinning out of control? How to combat burnout on the job.

PMID- 21950432
TI  - Software verification and validation: the role of IEC 60601-1.

PMID- 21950433
TI  - A new approach: software development and validation.

PMID- 21950434
TI  - The top five sterilization challenges.

PMID- 21950435
TI  - The use of mobile devices to improve alarm systems.

PMID- 21950436
TI  - Medical imaging advocate tackles industry challenges.

PMID- 21950437
TI  - Strategic planning process sets stage for success.

PMID- 21950438
TI  - CMS' Conditions of Participation Vs. ISO 9001 Requirements.

PMID- 21950439
TI  - X-ray film processors.

PMID- 21950440
TI  - Have you been scrumped?

PMID- 21950441
TI  - How to use financial benchmarks.

PMID- 21950442
TI  - Electrosurgical units and life support equipment.

PMID- 21950443
TI  - Practical guidance for a broad audience.

PMID- 21950444
TI  - Predictions revisited, five years later.

PMID- 21950445
TI  - Device recalls and the recalling company's website.
AB  - An ongoing issue with respect to medical device recalls is getting the
      information to the right people in a timely manner so that appropriate action can
      be taken. For Class I recalls, this is often addressed by one or more means of
      professional and public communications, including after-the-fact posting of such
      recalls by the U.S. Food and Drug Administration (FDA). One resource that could
      be included in a recall strategy is the recalling company's own website where the
      information could be readily available in close association with other
      information on the product, and where it would be readily found by someone making
      a product specific inquiry. However an investigation of 13 Class I recalls from
      the 4th quarter of 2010 shows that only four of these included a web presence,
      and even among these, the recall information was not necessarily easily found,
      nor closely linked, to other product information.

PMID- 21950446
TI  - Being a (clinical) team player.

PMID- 21950447
TI  - Group testing for case identification with correlated responses.
AB  - This article examines group testing procedures where units within a group (or
      pool) may be correlated. The expected number of tests per unit (i.e., efficiency)
      of hierarchical- and matrix-based procedures is derived based on a class of
      models of exchangeable binary random variables. The effect on efficiency of the
      arrangement of correlated units within pools is then examined. In general, when
      correlated units are arranged in the same pool, the expected number of tests per
      unit decreases, sometimes substantially, relative to arrangements that ignore
      information about correlation.

PMID- 21950448
TI  - Prediction of additional lymph node positivity and clinical outcome of
      micrometastases in sentinel lymph nodes in cutaneous melanoma: a multi
      institutional study of 450 patients in Japan.
AB  - Various microscopic classifications of metastatic sentinel lymph nodes (SLN) have
      been reported along with predictors of additional lymph node positivity and their
      correlations with the prognosis. The purpose of this study was to re-evaluate
      these classifications in the Japanese population. We selected the following three
      classifications, based on the procedural simplicity of the measurements: maximum
      diameter (maximum diameter of the largest tumor lesion in the SLN; <0.1, 0.1-1.0,
      >1.0 mm), invasion depth (depth of tumor invasion measured from the capsule in
      the SLN; SI <= 0.3 mm, SII >0.3 to <= 1.0 mm, SIII >1.0 mm), and microanatomic
      location (microanatomic location of the tumor deposits within the SLN;
      "subcapsular", "parenchymal", "combined", "multifocal", "extensive"). A
      retrospective study, using prescribed survey forms, was carried out. Among the
      450 patients, including the 149 cases with SLN metastasis, an additional lymph
      node positivity rate of 0% could be predicted only in patients with a maximum
      diameter category of less than 0.1 mm. As compared with that in the SLN
      metastasis-negative cases, however, the prognosis was poorer in cases with SLN
      metastasis, even those with lesions falling under the maximum diameter category
      of less than 0.1 mm, invasion depth category of SI (<= 0.3 mm) and microanatomic
      location category of subcapsular. The prognosis is particularly poor for the
      microanatomic location category of extensive, which should thus be regarded as a
      macrometastasis. A prospective study with standardized procedures, including
      pathological evaluation, is needed in order to confirm our conclusion.

PMID- 21950449
TI  - Organ biodistribution, clearance, and genotoxicity of orally administered zinc
      oxide nanoparticles in mice.
AB  - Abstract   Understanding tissue biodistribution and clearance of zinc oxide
      nanoparticles (ZnO-NPs) is necessary for its risk assessment. Both fed and
      intraperitoneally injected ZnO-NPs (2.5 g/kg) were absorbed into circulation
      (within 30 min post-dosing), then biodistributed to the liver, spleen, and
      kidney. Intraperitoneally injected ZnO-NPs remained in serum for 72 h and could
      more effectively spread to the heart, lung, and testes, whereas the clearance for
      fed ZnO-NPs in serum began 6 h after oral administration. Compared with zinc
      oxide microparticles (ZnO-MPs), ZnO-NPs exhibited much higher absorptivity and
      tissue biodistribution in fed treatment. A greater fraction of fed ZnO-NPs
      localised in the liver resulted in transient histopathological lesions. However,
      superoxide generation and cytotoxicity were showed in vitro treatment with ZnO
      NPs (above 20 MUg/mL). Considering both in vitro and in vivo data, the ZnO-NPs
      induced acute liver toxicity which was in compliance with its absorption,
      biodistribution, and clearance.

PMID- 21950450
TI  - Differential effect of common ligands and molecular oxygen on antimicrobial
      activity of silver nanoparticles versus silver ions.
AB  - The antibacterial activity of silver nanoparticles (AgNPs) is partially due to
      the release of Ag(+), although discerning the contribution of AgNPs vs Ag(+) is
      challenging due to their common co-occurrence. We discerned the toxicity of Ag(+)
      versus a commercially available AgNP (35.4 +/- 5.1 nm, coated with amorphous
      carbon) by conducting antibacterial assays under anaerobic conditions that
      preclude Ag0 oxidation, which is a prerequisite for Ag(+) release. These AgNPs
      were 20* less toxic to E. coli than Ag(+) (EC50: 2.04 +/- 0.07 vs 0.10 +/- 0.01
      mg/L), and their toxicity increased 2.3-fold after exposure to air for 0.5 h
      (EC50: 0.87 +/- 0.03 mg/L) which promoted Ag(+) release. No significant
      difference in Ag(+) toxicity was observed between anaerobic and aerobic
      conditions, which rules out oxidative stress by ROS as an important antibacterial
      mechanism for Ag(+). The toxicity of Ag(+) (2.94 MUmol/L) was eliminated by
      equivalent cysteine or sulfide; the latter exceeded the solubility product
      equilibrium constant (K(sp)), which is conducive to silver precipitation.
      Equivalent chloride and phosphate concentrations also reduced Ag(+) toxicity
      without exceeding K(sp). Thus, some common ligands can hinder the bioavailability
      and mitigate the toxicity of Ag(+) at relatively low concentrations that do not
      induce silver precipitation. Furthermore, low concentrations of chloride (0.1
      mg/L) mitigated the toxicity of Ag(+) but not that of AgNPs, suggesting that
      previous reports of higher AgNPs toxicity than their equivalent Ag(+)
      concentration might be due to the presence of common ligands that preferentially
      decrease the bioavailability and toxicity of Ag(+). Overall, these results show
      that the presence of O2 or common ligands can differentially affect the toxicity
      of AgNPs vs Ag(+), and underscore the importance of water chemistry in the mode
      of action of AgNPs.

PMID- 21950451
TI  - A pilot comparison of laser-assisted vs piezo drill ICSI for the in vitro
      production of horse embryos.
AB  - Intracytoplasmic sperm injection (ICSI) is the method of choice for the in vitro
      production (IVP) of equine embryos. However, conventional ICSI has been
      associated with mechanical damage to the oocyte caused by the deformation of the
      zona pellucida (ZP) and exposure of the oolemma to negative pressure during
      injection. Introduction of the less traumatic and more efficient piezo drill
      assisted ICSI (PDAI) yielded higher cleavage rates and more consistent results.
      Nevertheless, PDAI is also associated with disadvantages such as the use of
      mercury and possible DNA damage. This led us to explore an alternative method
      avoiding oocyte trauma, namely laser-assisted ICSI (LAI), which involves creating
      a hole in the ZP prior to ICSI. In this pilot study, PDAI and LAI were compared
      for ICSI in the horse. No significant influences on subsequent embryonic
      development were observed.

PMID- 21950455
TI  - The effects of third-party validation and minimization on judgments of the
      transgressor and the third party.
AB  - Victims of interpersonal transgressions often turn to friends, family, and
      trusted others when trying to make sense of negative events. This research
      explored the effect of two of the many ways that these informal third parties can
      respond: validating the victim's experience, and downplaying or minimizing the
      transgression. Two studies found that validation from a third party increases
      revenge motivations and that minimization of the transgression is more effective
      than validation at reducing revenge motivations. However, results also indicated
      that victims judge third parties more positively if they validate rather than
      minimize the transgression. These findings suggest that, when choosing between
      validation and minimization, third parties must make a choice between promoting
      forgiveness and promoting themselves.

PMID- 21950456
TI  - Regional zooplankton biodiversity provides limited buffering of pond ecosystems
      against climate change.
AB  - 1. Climate change and other human-driven environmental perturbations are causing
      reductions in biodiversity and impacting the functioning of ecosystems on a
      global scale. Metacommunity theory suggests that ecosystem connectivity may
      reduce the magnitude of these impacts if the regional species pool contains
      functionally redundant species that differ in their environmental tolerances.
      Dispersal may increase the resistance of local ecosystems to environmental stress
      by providing regional species with traits adapted to novel conditions. 2. We
      tested this theory by subjecting freshwater zooplankton communities in mesocosms
      that were either connected to or isolated from the larger regional species pool
      to a factorial manipulation of experimental warming and increased salinity. 3.
      Compensation by regional taxa depended on the source of stress. Warming tolerant
      regional taxa partially compensated for reductions in heat sensitive local taxa
      but similar compensation did not occur under increased salinity. 4. Dispersal
      mediated species invasions dampened the effects of warming on summer net
      ecosystem productivity. However, this buffering effect did not occur in the fall
      or for periphyton growth, the only other ecosystem function affected by the
      stress treatments. 5. The results indicate that regional biodiversity can provide
      insurance in a dynamic environment but that the buffering capacity is limited to
      some ecosystem processes and sources of stress. Maintaining regional biodiversity
      and habitat connectivity may therefore provide some limited insurance for local
      ecosystems in changing environments, but is unable to impart resistance against
      all sources of environmental stress.

PMID- 21950457
TI  - Different in vitro and in vivo profiles of substituted 3-aminopropylphosphinate
      and 3-aminopropyl(methyl)phosphinate GABA(B)  receptor agonists as inhibitors of
      transient lower oesophageal sphincter relaxation.
AB  - BACKGROUND AND PURPOSE: Gastro-oesophageal reflux is predominantly caused by
      transient lower oesophageal sphincter relaxation (TLOSR) and GABA(B) receptor
      stimulation inhibits TLOSR. Lesogaberan produces fewer CNS side effects than
      baclofen, which has been attributed to its affinity for the GABA transporter
      (GAT), the action of which limits stimulation of central GABA(B) receptors. To
      understand the structure-activity relationship for analogues of lesogaberan (3
      aminopropylphosphinic acids), and corresponding 3-aminopropyl(methyl)phosphinic
      acids, we have compared representatives of these classes in different in vitro
      and in vivo models. EXPERIMENTAL APPROACH: The compounds were characterized in
      terms of GABA(B) agonism in vitro. Binding to GATs and cellular uptake was done
      using rat brain membranes and slices respectively. TLOSR was measured in dogs,
      and CNS side effects were evaluated as hypothermia in mice and rats. KEY RESULTS:
      3-Aminopropylphosphinic acids inhibited TLOSR with a superior therapeutic index
      compared to 3-aminopropyl(methyl)phosphinic acids. This difference was most
      likely due to differential GAT-mediated uptake into brain cells of the former but
      not latter. In agreement, 3-aminopropyl(methyl)phosphinic acids were much more
      potent in producing hypothermia in rats even when administered i.c.v. CONCLUSIONS
      AND IMPLICATIONS: An enhanced therapeutic window for 3-aminopropylphosphinic
      acids compared with 3-aminopropyl(methyl)phosphinic acids with respect to
      inhibition of TLOSR was observed and is probably mechanistically linked to neural
      cell uptake of the former but not latter group of compounds. These findings offer
      a platform for discovery of new GABA(B) receptor agonists for the treatment of
      reflux disease and other conditions where selective peripheral GABA(B) receptor
      agonism may afford therapeutic effects.

PMID- 21950458
TI  - Carbamazepine differentially affects the pharmacokinetics of fexofenadine
      enantiomers.
AB  - AIM: This aim of this study was to characterize the impact of the P-glycoprotein
      (P-gp) inducer, carbamazepine, on fexofenadine enantiomer pharmacokinetics.
      METHODS: Twelve healthy volunteers initially received a 60mg dose of fexofenadine
      alone. Subsequently, a 100mg dose of carbamazepine was administered three times
      daily (300mg day(-1) ), and on day 7, fexofenadine was co-administered. RESULTS:
      Carbamazepine significantly decreased the area under the plasma concentration
      time curve and the amount excreted into the urine of (S)- and (R)-fexofenadine.
      The P-gp inducer showed a greater effect on the pharmacokinetic parameters of (S)
      fexofenadine. CONCLUSION: This study indicates that carbamazepine may alter the
      pharmacokinetics of fexofenadine enantiomers.

PMID- 21950459
TI  - Contact dermatitis caused by bufexamac sparing the eruption of herpes zoster.

PMID- 21950460
TI  - Confinement effects and hyperfine structure in se doped silicon nanowires.
AB  - We report a density functional study of the electronic properties and hyperfine
      structure of substitutional selenium in silicon nanowires using plane-wave
      pseudopotential techniques. We simulated hydrogen passivated [001] oriented
      nanowires with a diameter up to 2 nm, analyzing the effect of quantum confinement
      on the defect formation energy and on the hyperfine parameters as a function of
      the diameter and of the defect position. We show that substitutional Se in
      silicon has favorable configurations for positions near the surface with possible
      formation of chalcogen-hydrogen complexes. We also show that hyperfine
      interactions increase at small diameters, as long as the nanowire is large enough
      to prevent surface distortion which modifies the symmetry of the donor wave
      function. Moreover, surface effects lead to strong differences in the hyperfine
      parameters depending on the Se location inside the nanowire, allowing the
      identification of an impurity site on the basis of electron paramagnetic
      resonance spectra.

PMID- 21950461
TI  - An FCS study of unfolding and refolding of CPM-labeled human serum albumin: role
      of ionic liquid.
AB  - The effect of a room temperature ionic liquid (RTIL) on the conformational
      dynamics of a protein, human serum albumin (HSA), is studied by fluorescence
      correlation spectroscopy (FCS). For this, the protein was covalently labeled by a
      fluorophore, 7-dimethylamino-3-(4-maleimidophenyl)-4-methylcoumarin (CPM). On
      addition of a RTIL ([pmim][Br]) to the native protein, the diffusion coefficient
      (D(t)) decreases and the hydrodynamic radius (R(h)) increases. This suggests that
      the RTIL ([pmim][Br]) acts as a denaturant when the protein is in the native
      state. However, addition of [pmim][Br] to a protein denatured by GdnHCl causes an
      increases in D(t) and decrease in R(h). This suggests that in the presence of
      GdnHCl addition of RTIL helps the protein to refold. In the native state, the
      conformational dynamics of protein is described by three distinct time constants:
      ~3.6 +/- 0.7, ~29 +/- 4.5, and 133 +/- 23 MUs. The faster components (~3.6 +/-
      0.7 and ~29 +/- 4.5 MUs) are ascribed to chain dynamics of the protein, while the
      slowest component (133 MUs) is responsible for interchain interaction or
      concerted motion. On addition of [pmim][Br], the conformational dynamics of HSA
      becomes slower (~5.1 +/- 1, ~43.5 +/- 2.8, and ~311 +/- 2.3 MUs in the presence
      of 1.5 M [pmim][Br]). The time constants for the protein denatured by 6 M GdnHCl
      are 3.2 +/- 0.4, 34 +/- 6, and 207 +/- 38 MUs. When 1.5 M [pmim][Br] is added to
      the denatured protein (in 6 M GdnHCl), the time constants become ~5 +/- 1, ~41 +/
      10, and ~230 +/- 45 MUs. The lifetime histogram shows that, on addition of
      GdnHCl to HSA, the contribution of the shorter lifetime component decreases and
      vanishes at 6 M GdnHCl. The shorter lifetime component immediately reappears
      after addition of RTIL to unfolded HSA. This suggests recoiling of the unfolded
      protein by RTIL.

PMID- 21950462
TI  - Ubiquitin-activating enzyme (UBA1) is required for sperm capacitation, acrosomal
      exocytosis and sperm-egg coat penetration during porcine fertilization.
AB  - Protein ubiquitination is a stable, covalent post-translational modification that
      alters protein activity and/or targets proteins for proteolysis by the 26S
      proteasome. The E1-type ubiquitin-activating enzyme (UBA1) is responsible for
      ubiquitin activation, the initial step of ubiquitin-protein ligation. Proteasomal
      proteolysis of ubiquitinated spermatozoa and oocyte proteins occurs during
      mammalian fertilization, particularly at the site of sperm acrosome contact with
      oocyte zona pellucida. However, it is not clear whether the substrates are solely
      proteins ubiquitinated during gametogenesis or if de novo ubiquitination also
      occurs during fertilization supported by ubiquitin-activating and -conjugating
      enzymes present in the sperm acrosome. Along this line of inquiry, UBA1 was
      detected in boar sperm-acrosomal extracts by Western blotting (WB).
      Immunofluorescence revealed accumulation of UBA1 in the nuclei of spermatogonia,
      spermatocytes and spermatids, and in the acrosomal caps of round and elongating
      spermatids. Thiol ester assays utilizing biotinylated ubiquitin and isolated
      sperm acrosomes confirmed the enzymatic activity of the resident UBA1. A specific
      UBA1 inhibitor, PYR-41, altered the remodelling of the outer acrosomal membrane
      (OAM) during sperm capacitation, monitored using flow cytometry of fluorescein
      isothiocyanate-conjugated peanut agglutinin (FITC-PNA). Although viable and
      motile, the spermatozoa capacitated in the presence of PYR-41, showed
      significantly reduced fertilization rates during in vitro fertilization (IVF; p <
      0.05). Similarly, the fertilization rate was lowered by the addition of PYR-41
      directly into fertilization medium during IVF. In WB, high Mr bands, suggestive
      of protein ubiquitination, were detected in non-capacitated spermatozoa by
      antibodies against ubiquitin; WB with anti-phosphotyrosine antibodies and
      antibodies against acrosomal proteins SPINK2 (acrosin inhibitor) and AQN1
      (spermadhesin) revealed that the capacitation-induced modification of those
      proteins was altered by PYR-41. In summary, it appears that de novo protein
      ubiquitination involving UBA1 contributes to sperm capacitation and acrosomal
      function during fertilization.

PMID- 21950463
TI  - The association between EMS workplace safety culture and safety outcomes.
AB  - BACKGROUND: Prior studies have highlighted wide variation in emergency medical
      services (EMS) workplace safety culture across agencies. OBJECTIVE: To determine
      the association between EMS workplace safety culture scores and patient or
      provider safety outcomes. METHODS: We administered a cross-sectional survey to
      EMS workers affiliated with a convenience sample of agencies. We recruited these
      agencies from a national EMS management organization. We used the EMS Safety
      Attitudes Questionnaire (EMS-SAQ) to measure workplace safety culture and the EMS
      Safety Inventory (EMS-SI), a tool developed to capture self-reported safety
      outcomes from EMS workers. The EMS-SAQ provides reliable and valid measures of
      six domains: safety climate, teamwork climate, perceptions of management, working
      conditions, stress recognition, and job satisfaction. A panel of medical
      directors, emergency medical technicians and paramedics, and occupational
      epidemiologists developed the EMS-SI to measure self-reported injury, medical
      errors and adverse events, and safety-compromising behaviors. We used
      hierarchical linear models to evaluate the association between EMS-SAQ scores and
      EMS-SI safety outcome measures. RESULTS: Sixteen percent of all respondents
      reported experiencing an injury in the past three months, four of every 10
      respondents reported an error or adverse event (AE), and 89% reported safety
      compromising behaviors. Respondents reporting injury scored lower on five of the
      six domains of safety culture. Respondents reporting an error or AE scored lower
      for four of the six domains, while respondents reporting safety-compromising
      behavior had lower safety culture scores for five of the six domains.
      CONCLUSIONS: Individual EMS worker perceptions of workplace safety culture are
      associated with composite measures of patient and provider safety outcomes. This
      study is preliminary evidence of the association between safety culture and
      patient or provider safety outcomes.

PMID- 21950464
TI  - Capecitabine for the treatment for advanced gastric cancer: efficacy, safety and
      ethnicity.
AB  - WHAT IS KNOWN AND OBJECTIVE: Capecitabine- and 5-fluorouracil (5-FU)-based
      regimens are widely used for the treatment for advanced gastric cancer (AGC). We
      aimed to compare the efficacy of the two regimens for both Caucasian and Asian
      subjects, through a meta-analysis of the available trial evidence. METHODS: We
      searched PubMed, ASO, ECCO, ESMO, Wanfang database (Chinese), CNKI (Chinese),
      Weipu database (Chinese) and J-STAGE (Japanese) using combinations of keywords,
      including 'capecitabine', '5-fluorouracil', 'chemotherapy', 'stomach neoplasms'
      and 'gastric cancer'. We identified relevant trial evidence and pooled the
      results on both efficacy and adverse events. RESULTS AND DISCUSSION: Capecitabine
      based chemotherapy for AGC prolonged the overall survival (OS; 10.7 months vs.
      9.5 months, P = 0.03) and enhanced the response rate (RR; OR = 1.32; 95% CI, 1.11
      1.57; P = 0.002) over 5-FU-based chemotherapy. Similar trends were observed in
      both Caucasian and Asian patients. Capecitabine-based regimens were associated
      with reduced incidence rates of grade 3 or grade 4 leukopenia (OR = 0.42; P =
      0.005), stomatitis (OR = 0.43; P = 0.004) and nausea and vomiting (OR = 0.60; P =
      0.002) compared with 5-FU-based treatment. Incidence of haematological toxicity
      such as anaemia (OR = 0.88; P = 0.53), thrombocytopenia (OR = 0.58; P = 0.06),
      neutropenia (OR = 1.03; P = 0.78) and treatment-related mortality was similar
      between capecitabine- and 5-FU-based treatments. Higher frequency of grade 3 or
      grade 4 hand-foot syndrome (HFS; OR 2.45; P = 0.0007) was observed in
      capecitabine-based combination therapies. Asian patients with AGC receiving
      capecitabine-based combination therapies showed less frequent occurrence of grade
      3 or grade 4 gastrointestinal toxicity including nausea and vomiting (OR = 0.24;
      P = 0.0002) and stomatitis (OR = 0.33; P = 0.02) than those receiving 5-FU-based
      regimens. These differences in GI toxicity between treatment regimens were not
      significant in Caucasian subjects. No significant difference was found for the
      occurrence of anaemia (Caucasian subgroup: OR = 0.97, P = 0.88; Asian subgroup:
      OR = 0.63, P = 0.29), neutropenia (Caucasian subgroup: OR = 1.16, P = 0.27; Asian
      subgroup: OR = 0.75, P = 0.21) or thrombocytopenia (Caucasian subgroup: OR =
      0.62, P = 0.18; Asian subgroup: OR = 0.51, P = 0.17) between the two ethnic
      subgroups. WHAT IS NEW AND CONCLUSION: Capecitabine-based chemotherapy strategies
      show prolonged OS and enhanced ORR compared with traditional 5-FU-based
      treatments and therefore should be considered as one of the first choices for
      treatment for AGC. Asian patients also showed less grade 3 or grade 4
      gastrointestinal toxicity with the capecitabine-based regimens.

PMID- 21950465
TI  - A new daunomycin-peptide conjugate: synthesis, characterization and the effect on
      the protein expression profile of HL-60 cells in vitro.
AB  - Daunomycin (Dau) is a DNA-binding antineoplastic agent in the treatment of
      various types of cancer, such as osteosarcomas and acute myeloid leukemia. One
      approach to improve its selectivity and to decrease the side effects is the
      conjugation of Dau with oligopeptide carriers, which might alter the drug uptake
      and intracellular fate. Here, we report on the synthesis, characterization, and
      in vitro biological properties of a novel conjugate in which Dau is attached, via
      an oxime bond, to one of the cancer specific small peptides (LTVSPWY) selected
      from a random phage peptide library. The in vitro cytostatic effect and cellular
      uptake of Dau?Aoa-LTVSPWY-NH(2) conjugate were studied on various human cancer
      cell lines expressing different levels of ErbB2 receptor which could be targeted
      by the peptide. We found that the new daunomycin-peptide conjugate is highly
      cytostatic and could be taken up efficiently by the human cancer cells studied.
      However, the conjugate was less effective than the free drug itself. RP-HPLC data
      indicate that the conjugate is stable at least for 24 h in the pH 2.5-7.0 range
      of buffers, as well as in cell culture medium. The conjugate in the presence of
      rat liver lysosomal homogenate, as indicated by LC-MS analysis, could be
      degraded. The smallest, Dau-containing metabolite (Dau?Aoa-Leu-OH) identified and
      prepared expresses DNA-binding ability. In order to get insight on the potential
      mechanism of action, we compared the protein expression profile of HL-60 human
      leukemia cells after treatment with the free and peptide conjugated daunomycin.
      Proteomic analysis suggests that the expression of several proteins has been
      altered. This includes three proteins, whose expression was lower (tubulin beta
      chain) or markedly higher (proliferating cell nuclear antigen and protein kinase
      C inhibitor protein 1) after administration of cells with Dau-conjugate vs free
      drug.

PMID- 21950466
TI  - Characteristics of Thoroughbred and Quarter Horse racehorses that sustained a
      complete scapular fracture.
AB  - REASONS FOR PERFORMING STUDY: To determine if scapular fractures occur in
      racehorses with distinctive characteristics. OBJECTIVES: To test the hypothesis
      that Thoroughbred (TB) and Quarter Horse (QH) racehorses with a scapular fracture
      have similar characteristics that are different from those of their respective
      racetrack populations. METHODS: Necropsy findings, case details, last race
      information and career earnings for TB and QH racehorses that had a scapular
      fracture in California between 1990 and 2008 were retrospectively compared
      between breeds. Horse signalment, career earnings, career starts and race
      characteristics were obtained for all California racehorses. Comparisons were
      made between affected horses, other racehorses that died, and all horses that
      raced, in California during the 19 year period. RESULTS: Seventy-three TB and 28
      QH racehorses had a similar, complete comminuted scapular fracture with an
      articular component, and right forelimb predilection. The QHs had a higher
      incidence of scapular fracture incurred during racing than TBs (0.98 vs.
      0.39/1000 starters). The TB and QH incident rates for musculoskeletal deaths
      incurred racing were 20.5 and 17.5/1000 starters, respectively; however, a
      greater proportion of TB musculoskeletal deaths occurred training (40% vs. 8%).
      Horses with a scapular fracture were more likely to be male and aged 2 or >= 5
      years than the racetrack population. Most affected QHs (64%) were 2-year-olds;
      most TBs (74%) were aged >= 3 years. Scapular fractures occurred more commonly
      during racing in QHs (70%) than TBs (44%). Race-related scapular fracture was
      more likely to occur in a Maiden race than in a non-Maiden race. Horses with a
      scapular fracture had fewer career starts than the racetrack population.
      CONCLUSIONS AND POTENTIAL RELEVANCE: Despite breed differences for signalment and
      exercise distances, both breeds incur a complete scapular fracture that is more
      likely to occur in the right scapula of young and older, male racehorses, early
      in their race career or after few races. Quarter Horses sustain a catastrophic
      scapular fracture more frequently than TBs.

PMID- 21950467
TI  - Preventing tobacco companies from advertising using their packaging could be an
      important component of comprehensive tobacco control: a commentary on Australia's
      plain packaging of cigarettes.

PMID- 21950468
TI  - The influence of bearing cycles on olive oil quality response to irrigation.
AB  - Five rates of water application were applied in a 4 year study on olive (Olea
      europaea) varieties 'Barnea' and 'Souri'. Increased irrigation lead to increased
      tree-scale oil yields, lower polyphenol content, and, frequently, higher oil
      acidity. These effects were predominant in "off" years. The fatty acid profile
      was influenced primarily by bearing level and variety and secondarily by
      irrigation rate. The saturated to unsaturated fatty acid ratio was higher in
      "off" than in "on" years, and the monounsaturated fatty acid to polyunsaturated
      fatty acid ratio was higher in "on" years as a result of the fact that oleic and
      stearic acids were higher in "on" years, while palmitic, palmitoleic, and
      linoleic acids were greater in "off" years. Squalene was higher in 'Souri' than
      in 'Barnea' oils, was not affected by bearing cycle, and was consistently lower
      in oil from trees receiving the lowest irrigation level.

PMID- 21950469
TI  - Investigation of unanticipated alkylation at the N(pi) position of a histidyl
      residue under Mitsunobu conditions and synthesis of orthogonally protected
      histidine analogues.
AB  - We had previously reported that Mitsunobu-based introduction of alkyl
      substituents onto the imidazole N(pi)-position of a key histidine residue in
      phosphothreonine-containing peptides can impart high binding affinity against the
      polo-box domain of polo-like kinase 1. Our current paper investigates the
      mechanism leading to this N(pi)-alkylation and provides synthetic methodologies
      that permit the facile synthesis of histidine N(pi)-modified peptides. These
      agents represent new and potentially important tools for biological studies.

PMID- 21950470
TI  - Permutation tests for random effects in linear mixed models.
AB  - Inference regarding the inclusion or exclusion of random effects in linear mixed
      models is challenging because the variance components are located on the boundary
      of their parameter space under the usual null hypothesis. As a result, the
      asymptotic null distribution of the Wald, score, and likelihood ratio tests will
      not have the typical chi(2) distribution. Although it has been proved that the
      correct asymptotic distribution is a mixture of chi(2) distributions, the
      appropriate mixture distribution is rather cumbersome and nonintuitive when the
      null and alternative hypotheses differ by more than one random effect. As
      alternatives, we present two permutation tests, one that is based on the best
      linear unbiased predictors and one that is based on the restricted likelihood
      ratio test statistic. Both methods involve weighted residuals, with the weights
      determined by the among- and within-subject variance components. The null
      permutation distributions of our statistics are computed by permuting the
      residuals both within and among subjects and are valid both asymptotically and in
      small samples. We examine the size and power of our tests via simulation under a
      variety of settings and apply our test to a published data set of chronic
      myelogenous leukemia patients.

PMID- 21950471
TI  - Field effect in oral precancer as assessed by DNA flow cytometry and array-CGH.
AB  - OBJECTIVE: 'Field cancerization' is an accepted model for oral carcinogenesis. So
      far, genetically altered fields have been just reported in the presence of
      carcinomas. This study assessed the distant mirror fields (MFs) of oral precancer
      by DNA high-resolution flow cytometry (hr DNA-FCM) and array-Comparative Genomic
      Hybridization (a-CGH). METHODS: Five leukoplakias without dysplasia (OLs), seven
      dysplastic leukoplakias (DOLs), and 12 corresponding visually normal and non
      dysplastic MFs were analyzed. DNA aneuploidy (DNA Index, DI ? 1) was detected by
      hr DNA-FCM on DAPI stained nuclei suspensions. The epithelial DNA aneuploid
      subclones were FCM-sorted to obtain genomic DNA for a-CGH. RESULTS: Mirror
      fields, OLs, and DOLs showed increasing prevalence of DNA aneuploidy of,
      respectively, 8%, 20%, and 57%. The average number of chromosome aberrations (Ch
      Abs) was 2.8 in MFs, 3 in OLs, and 10.6 in DOLs. MFs relative to OLs and DOLs had
      average numbers of Ch-Abs, respectively, of 1.8 and 3.6. Ch-Abs were also
      observed in DNA diploid sublines, and often the same aberrations were observed in
      both MFs and corresponding OLs/DOLs. CONCLUSION: DNA aneuploidy and Ch-Abs in
      MFs, the last ones being mainly gains, indicate an early onset of field effect in
      oral carcinogenesis.

PMID- 21950477
TI  - Two cases of erythema exsudativum multiforme associated with Chlamydia pneumoniae
      infection.
AB  - We report two cases of erythema exsudativum multiforme (EEM) that we concluded
      were caused by infections with Chlamydia pneumoniae. High titers of IgG antibody
      for Chlamydia pneumoniae were shown in the sera of both cases. One case showed
      the classical symptoms of pneumonia together with radiological changes in the
      chest; the other case did not show these symptoms. To the best of our knowledge,
      only three cases of erythema multiforme associated with Chlamydia pneumoniae
      infection have been reported.

PMID- 21950478
TI  - By any means necessary: the effects of regulatory focus and moral conviction on
      hostile and benevolent forms of collective action.
AB  - In two studies, we investigate the effect of individuals' promotion and
      prevention focus on engagement in collective action. We show that responding to
      group-based disadvantage out of a sense of moral conviction motivates prevention
      oriented- but not promotion-oriented- individuals to engage in collective action.
      Furthermore, holding such strong moral convictions about the fair treatment of
      their group causes the prevention-oriented to disregard societal rules against
      hostile forms of collective action (i.e., forms of action that are aimed at
      harming the interests of those held responsible for the group's disadvantage).
      Study 1 showed that prevention-oriented individuals, but not promotion-oriented
      individuals, with a strong moral conviction about the fair treatment of their
      group are willing to support both hostile and benevolent forms of collective
      action. Study 2 replicated this effect and showed that for prevention-oriented
      individuals but not for promotion-oriented individuals, holding a strong moral
      conviction about the fair treatment of the group overrides moral objections to
      hostile forms of collective action in the decision to support these forms of
      action.

PMID- 21950479
TI  - Pelvic dimensions in phenotypically double-muscled Belgian Blue cows.
AB  - Some anatomical characteristics of 507 Belgian Blue (BB) cattle, withers height
      (WH), heart girth (HG), the distance between the two tubera coxae (TcTc) and the
      distance between the two tubera ischiadica (TiTi), were compared with the
      internal pelvic measurements of width, height and area. Mean values were 58.9 +/-
      6.2 cm for TcTc, 14.6 +/- 2.3 cm for TiTi, 15.2 +/- 2.1 cm for pelvic width (PW),
      18.8 +/- 1.9 cm for pelvic height (PH) and 288.5 +/- 60.9 cm(2) for pelvic area
      (PA). Cows that calved per vaginam had larger WH (p < 0.05), TcTc (p < 0.05) and
      TiTi (p < 0.001) and internal pelvic measurements [PH and PA (p < 0.001)]
      compared with those whose parturition was managed by caesarean section (CS):
      Correlations between internal pelvic measurements and TcTc were higher (r = 0.58
      0.63) than TiTi (r = 0.22-0.28). Correlations between other external body
      measures such as HG and WH with the internal pelvic measurements were even higher
      for HG (r = 0.69-0.74) and for WH (r = 0.67-0.74). HG and WH, together with
      internal pelvic measures, may be added to estimated breeding values (EBV's) that
      should assist breeders in selecting cows that can calve per vaginam, thereby
      reducing the breed's dependence on elective CS for maintaining its unique
      characteristics.

PMID- 21950480
TI  - Investigation of the cytotoxicity of nanozeolites A and Y.
AB  - Nanosized zeolite particles are important materials for many applications in the
      field of nanotechnology. The possible adverse effects of these nanomaterials on
      human health have been scarcely investigated and remain largely unknown. This
      study reports the synthesis of nanozeolites Y and A with particle sizes of 25-100
      nm and adequate colloidal stability for in vitro cytotoxicity experiments. The
      cytotoxic response of macrophages, epithelial and endothelial cells to these
      nanocrystals was assessed by determining mitochondrial activity (MTT assay) and
      cell membrane integrity (LDH leakage assay). After 24 h of exposure, no
      significant cytotoxic activity was detected for nanozeolite doses up to 500
      MUg/ml. The addition of fetal calf serum to the cell culture medium during
      exposure did not significantly change this low response. The nanozeolites showed
      low toxicity compared with monodisperse amorphous silica nanoparticles of similar
      size (60 nm). These results may contribute to the application of safe
      nanozeolites for purposes such as medical imaging, sensing materials, low-k films
      and molecular separation processes.

PMID- 21950481
TI  - The effects of including a callous-unemotional specifier for the diagnosis of
      conduct disorder.
AB  - BACKGROUND: 'With Significant Callous-Unemotional Traits' has been proposed as a
      specifier for conduct disorder (CD) in the upcoming revision of the Diagnostic
      and Statistical Manual of Mental Disorders (DSM-V). The impact of this specifier
      on children diagnosed with CD should be considered. METHODS: A multi-site cross
      sectional design with volunteers (n = 1136) in the third-seventh grades and 566
      consecutive referrals (ages 5-18) to a community mental health center were used
      to estimate the prevalence rates of CD with and without the proposed specifier.
      In addition, the degree of emotional and behavioral (especially physical
      aggression) disturbance and level of impairment in youth with and without CD and
      with and without the specifier was evaluated. RESULTS: In the community sample,
      10%-32% of those with CD and 2%-7% of those without CD met the callous
      unemotional (CU) specifier threshold depending on informant. In the clinic
      referred sample, 21%-50% of those with CD and 14%-32% without CD met the CU
      specifier threshold depending on informant. Those with CD and the specifier
      showed higher rates of aggression in both samples and higher rates of cruelty in
      the clinic-referred sample. CONCLUSIONS: Results indicate between 10% and 50% of
      youth with CD would be designated with the proposed CU specifier. Those with CD
      and the specifier appear to be more severe on a number of indices, including
      aggression and cruelty.

PMID- 21950482
TI  - Microbial conversion of glycerol: present status and future prospects.
AB  - Biodiesel has emerged as a potential alternate renewable liquid fuel in the past
      two decades. Total annual production of biodiesel stands at 6.96 million tons and
      11.2 million tons in USA and Europe, respectively. In other countries, Asia and
      Latin America, biodiesel production has increased at unprecedented rate. Despite
      this, the economy of biodiesel is not attractive. An obvious solution for
      boosting the economy of the biodiesel industry is to look for markets for side
      products of the transesterification process of biodiesel synthesis. The main by
      product is glycerol. However, this glycerol is contaminated with alkali/acid
      catalyst and alcohol, and thus, is not useful for conventional applications such
      as in toothpaste, drugs, paints and cosmetics. Conversion of this glycerol to
      value-added product is a viable solution for effective and economic utilization,
      which would also generate additional revenue for the biodiesel industry.
      Intensive research has taken place in area of conversion of glycerol to numerous
      products. The conventional catalytic route of glycerol transformation employs
      prohibitively harsh conditions of temperature and pressure, and thus, has slim
      potential for large-scale implementation. In addition, the selectivity of the
      process is rather small with formation of many undesired side products. The
      bioconversion processes, on the other hand, are highly selective although with
      slower kinetics. In this review, we have given an assessment and overview of the
      literature on bioconversion of glycerol. We have assessed as many as 23 products
      from glycerol bioconversion, and have reviewed the literature in terms of
      microorganism used, mode of fermentation, type of fermentor, yield and
      productivity of the process and recovery/purification of the products. The
      metabolic pathway of conversion of glycerol to various products has been
      discussed. We have also pondered over economic and engineering issues of large
      scale implementation of process and have outlined the constraints and limitations
      of the process. We hope that this review will be a useful source of information
      for biochemists, biotechnologists, microbiologists and chemical engineers working
      in the area of glycerol bioconversion.

PMID- 21950483
TI  - Human sperm DNA oxidation, motility and viability in the presence of L-carnitine
      during in vitro incubation and centrifugation.
AB  - In vitro incubation and centrifugation is known to decrease human sperm quality.
      In the human body, besides its antioxidant effects, L-carnitine (LC) facilitates
      the transport of activated fatty acids from the cytosol to the mitochondrial
      matrix. In this study, we investigated the effect of LC on human sperm motility,
      viability and DNA oxidation after incubation and centrifugation, following the
      sperm preparation protocols of assisted reproduction. Normozoospermic semen
      samples (n = 55) were analysed according to the World Health Organization (WHO)
      guidelines. LC concentrations that are not toxic to spermatozoa as determined by
      sperm motility and viability were standardised after 2 and 4 h of incubation at
      37  degrees C. Semen samples to which the optimal LC concentrations were added
      were also centrifuged for 20 min at 300 g and analysed for sperm motility,
      viability and DNA oxidation. Sperm motility was improved at 0.5 mg ml(-1) LC
      after incubation and centrifugation with 5 * 10(6) sperm ml(-1). Higher
      concentration of LC (50 mg ml(-1)) significantly decreased sperm motility and
      viability. LC did not alter the baseline of sperm DNA oxidation during both
      incubation and centrifugation. In conclusion, LC may enhance sperm motility
      following incubation and centrifugation, while it might not affect sperm
      viability and DNA oxidation.

PMID- 21950484
TI  - The needs of denture-brushing in geriatrics: clinical aspects and perspectives.
AB  - INTRODUCTION: Oral and denture hygiene are often defective in particular with
      dependent persons such as geriatric subjects. The reasons are the lack of hygiene
      education of the subjects or those caring for them. Consequently, oral hygiene is
      often neglected, resulting in poor oral health and an increase in the presence of
      local or general infections. OBJECTIVE: This paper is a report of brushing
      effectiveness on microbial biofilm deposits on dentures of subjects participating
      in a specific oral hygiene programme. MATERIALS AND METHODS: Thirty-nine dentures
      of 30 subjects were assessed for 2 weeks following an educational brushing
      programme. Microbial biofilm was recovered using fluoresceine and then scanned
      and quantified by 'Mesurim' software three times: before study, after 1 and 2
      weeks. RESULTS: The repeated measurement procedures showed a decrease in the
      percentage of biofilm present (F = 15, p < 0.001) whatever the type of denture
      (partial or complete) and for all biomaterials. CONCLUSION: Regular denture
      brushing can improve local hygiene. Consequently, decreasing the biofilm surface
      can reduce the prevalence of oral pathogens, thereby contributing to the general
      prevention of the risks of infections such as pneumotisis.

PMID- 21950485
TI  - Two-photon fluorescence vascular bioimaging with new bioconjugate probes
      selective toward the vascular endothelial growth factor receptor 2.
AB  - We report the synthesis and characterization of two amine reactive fluorescent
      dyes with efficient two-photon absorption (2PA) properties and high fluorescence
      quantum yields. Bioconjugation of these dyes with the DC-101 antibody proved to
      be useful for selectively imaging the vascular endothelial growth factor receptor
      2 (VEGFR-2) in cells expressing this receptor in vitro and in "whole" mounted
      excised tumors (ex vivo) by two-photon fluorescence microscopy (2PFM). The
      penetration depths reached within the tumors by 2PFM was over 800 MUm. In
      addition, the concentration of dye required for incubation of these bioconjugates
      was in the picomolar domain, the probes possessed very good photostability, and
      the 2PFM setup did not require any additional means of increasing the collection
      efficiencies of fluorescent photons to achieve the relatively deep tissue imaging
      that was realized, due, in large part, to the favorable photophysical properties
      of the new probes.

PMID- 21950486
TI  - Effects of P2Y(1)  receptor antagonism on the reactivity of platelets from
      patients with stable coronary artery disease using aspirin and clopidogrel.
AB  - BACKGROUND AND PURPOSE: P2Y(1) is a purine receptor that triggers platelet
      aggregation. Its inhibition was studied in patients with stable coronary artery
      disease (CAD) receiving standard anti-platelet therapy. EXPERIMENTAL APPROACH:
      Blood samples from 10 patients on aspirin therapy (ASA, 80 mg.day(-1) ) were
      withdrawn before and 24 h after the administration of 450 mg clopidogrel (ASA/C)
      and were anti-coagulated with citrate or hirudin/PPACK in the presence or absence
      of the P2Y(1 ) inhibitor MRS2179 (M, 100 uM). Platelet responses to ADP (2.5 uM)
      and TRAP (2.5 uM), and collagen-induced thrombosis under flow conditions were
      analysed. KEY RESULTS: Compared with ASA, ASA + M strongly inhibited ADP-induced
      peak platelet aggregation (88%), late aggregation (84%), P-selectin expression
      (85%) and alpha(IIb) beta(3) activation (62%) (28%, 65%, 70% and 51% inhibition,
      respectively, for ASA/C vs. ASA). ASA + M also inhibited platelet/monocyte and
      platelet/neutrophil conjugate formation by 69% and 71% (57% and 59% for ASA/C vs.
      ASA). In TRAP-activated blood, ASA + M unexpectedly inhibited alpha(IIb) b(3)
      activation by 30%. In blood perfused in collagen-coated glass capillaries (shear
      rate of 1500 s(-1) ), ASA/C prevented thrombus growth beyond 5 min in relation to
      thrombus fragments embolization. ASA + M with or without clopidogrel completely
      prevented thrombus formation. Finally, ex vivo addition of MRS2179 and ASA to the
      blood of healthy donors markedly blocked thrombus formation on collagen in flow
      conditions, in contrast to ASA plus the P2Y(12) inhibitor 2-MeSAMP. CONCLUSIONS
      AND IMPLICATIONS: Through particularly efficient complementarities with ASA to
      inhibit platelet activation and thrombus formation, the inhibition of P2Y(1) in
      the blood of patients with CAD appears to play a more important role than
      previously anticipated.

PMID- 21950487
TI  - Efficacy and safety of dose-modified docetaxel plus cisplatin-based induction
      chemotherapy in Asian patients with locally advanced head and neck cancer.
AB  - WHAT IS KNOWN AND OBJECTIVE: The beneficial effects of docetaxel plus cisplatin
      based induction chemotherapy for patients with unresectable, advanced head and
      neck cancer (HNC) have been documented in Western countries. However, the
      efficacy of such treatment has not been confirmed in Asian patients. We aimed to
      determine whether incorporation of dose-modified docetaxel into a cisplatin-based
      induction regimen would be both effective and tolerable in our Asian population
      of patients. METHODS: Thirty-six patients with stage III or IV HNC who had
      undergone cisplatin-based induction chemotherapy were included in the current
      analysis. Fifty-three percentage of the patients had received induction
      chemotherapy with bolus cisplatin and continuous 5-fluorouracil (PF group), while
      the remaining 47% had additionally received dose-modified docetaxel (TPF group).
      We assessed the relative impact of the two treatments on clinical outcomes and
      treatment-related toxicities. RESULTS AND DISCUSSION: The disease control rate
      was higher in the TPF group (92.9% vs. 76.5%), although the difference did not
      reach statistical significance (P = 0.217). Addition of docetaxel increased the
      median progression-free survival to 435 days, which was 2.3 times longer than
      that (188 days) of patients not receiving docetaxel (P = 0.019). Non
      haematological toxicity profile was similar and acceptable in both treatment
      groups. Higher incidence of grade 3/4 neutropenia and more episodes of
      neutropenic fever-related hospitalization occurred in the docetaxel-treated
      patients, but most of them were managed uneventfully. WHAT IS NEW AND CONCLUSION:
      Addition of dose-modified docetaxel to cisplatin-based induction chemotherapy was
      both efficacious and generally safe. Docetaxel addition significantly prolonged
      progression-free survival and had an acceptable safety profile in our Asian
      population of patients with locoregionally advanced HNC.

PMID- 21950488
TI  - Core/shell Cu@Ag nanoparticle: a versatile platform for colorimetric
      visualization of inorganic anions.
AB  - Recognition and sensing of anions in aqueous media have been of considerable
      interest while remaining a challenging task up to date. In this document, we wish
      to present a simple yet sensitive method to detect inorganic anions by
      colorimetry based on the citrate-stabilized core/shell Cu@Ag nanoparticle (NP).
      It was found that the NP could discriminate some specific anions (Cl(-), Br(-),
      I(-), S(2-), and SCN(-)) from a wide range of environmentally dominant anions (F(
      ), SO(4)(2-), H(2)PO(4)(-), CO(3)(2-), NO(3)(-), etc), identified by the change
      in the color of the buffered NP solution or the surface plasmon resonance (SPR)
      absorbance band in the UV-vis spectrum. Among the recognized anions, four types
      of variation in the SPR absorption band were revealed. It was strongly enhanced
      for Cl(-) and Br(-) and was strongly damped for S(2-). For I(-), it first was
      slightly enhanced at lower concentrations and then gradually was damped at higher
      concentrations. For SCN(-), it first was slightly damped at lower concentrations
      and then was strongly enhanced at higher concentrations. In response to the
      optical change, the color of the NP solution turned from brown to bright yellow
      for Cl(-) (1 mM), Br(-) (10 MUM), and SCN(-) (50 MUM) to brownish orange for I(-)
      (10 MUM) and to reddish orange for S(2-) (50 MUM). The reason for these phenomena
      was postulated by the evidence of transmission electron microscope (TEM) images,
      X-ray photoelectron spectroscopy (XPS), and zeta potentials. In view of the
      importance of anions in the environment and for human health, the Cu@Ag NP
      colorimetric platform may have some applications, such as discriminating
      household table salt (NaCl) from industrial salt (NaNO(2)), testing the quality
      and extent of a variety of waters, and so forth.

PMID- 21950489
TI  - Effective beats dramatic: a commentary on Australia's plain packaging of
      cigarettes.

PMID- 21950490
TI  - Nevoid basal carcinoma syndrome (Gorlin syndrome) and pronounced androgenic
      alopecia in a woman with a novel mutation p.Leu1159fsx32 in the PTCH gene.

PMID- 21950491
TI  - Quality and stability of edible oils enriched with hydrophilic antioxidants from
      the olive tree: the role of enrichment extracts and lipid composition.
AB  - Phenolic extracts from olive tree leaves and olive pomace were used to enrich
      refined oils (namely, maize, soy, high-oleic sunflower, sunflower, olive, and
      rapeseed oils) at two concentration levels (200 and 400 MUg/mL, expressed as
      gallic acid). The concentration of characteristic olive phenols in these extracts
      together with the lipidic composition of the oils to be enriched influenced the
      mass transfer of the target antioxidants, which conferred additional stability
      and quality parameters to the oils as a result. In general, all of the oils
      experienced either a noticeable or dramatic improvement of their quality
      stability parameters (e.g., peroxide index and Rancimat) as compared with their
      nonenriched counterparts. The enriched oils were also compared with extra virgin
      olive oil with a natural content in phenols of 400 MUg/mL. The healthy properties
      of these phenols and the scarce or nil prices of the raw materials used can
      convert oils in supplemented foods or even nutraceuticals.

PMID- 21950492
TI  - Regional differences in surgical intervention following medical termination of
      pregnancy provided by telemedicine.
AB  - OBJECTIVE: Analysis of factors influencing surgical intervention rate after home
      medical termination of pregnancy (TOP) by women in countries without access to
      safe services using the telemedical service 'Women on Web'. DESIGN: Cohort study.
      SETTING: Women with an unwanted pregnancy less than nine weeks pregnant who used
      the telemedicine service of Women on Web between February 2007 and September 2008
      and provided follow-up information. SAMPLE: Women who used medical TOP with a
      known follow up. METHODS: Information from the online consultation, follow-up
      form and emails was used to analyze the outcome of the TOP. MAIN OUTCOME
      MEASURES: Ongoing pregnancy, reason for surgical intervention, perceived
      complications and satisfaction. RESULTS: Of the 2 323 women who did the medical
      TOP and had no ongoing pregnancy, 289 (12.4%) received a surgical intervention.
      High rates were found in Eastern Europe (14.8%), Latin America (14.4%) and
      Asia/Oceania (11.0%) and low rates in Western Europe (5.8%), the Middle East
      (4.7%) and Africa (6.1%; p=0.000). More interventions occurred with longer
      gestational age (p=0.000). Women without a surgical intervention more frequently
      reported satisfaction with the treatment (p=0.000). CONCLUSIONS: The large
      regional differences in the rates of reported surgical interventions after
      medical TOP provided by telemedicine cannot be explained by demographic factors
      or differences in gestational length. It is likely that these differences reflect
      different clinical practice and local guidelines on (incomplete) abortion rather
      than complications that genuinely needed surgical intervention. Surgical
      interventions significantly influenced womens' views on the acceptability of the
      TOP.

PMID- 21950493
TI  - Glass transition dynamics of room-temperature ionic liquid 1-methyl-3
      trimethylsilylmethylimidazolium tetrafluoroborate.
AB  - The conductivity relaxation dynamics of the room-temperature ionic liquid 1
      methyl-3-trimethylsilylmethylimidazolium tetrafluoroborate ([Si-MIm][BF(4)]) have
      been studied by broadband conductivity relaxation measurements at ambient
      pressure and elevated pressures up to 600 MPa. For the first time, several novel
      features of the dynamics have been found in a room-temperature ionic liquid. In
      the electric loss modulus M"(f) spectra, a resolved secondary beta-conductivity
      relaxation appears, and its relaxation time tau(beta) shifts on applying pressure
      in concert with the relaxation time tau(alpha) of the primary alpha-conductivity
      relaxation. The spectral dispersion of the alpha-conductivity relaxation, as well
      as the fractional exponent (1 - n) of the Kohlrausch-Williams-Watts function that
      fits the spectral dispersion, is invariant to various combinations of pressure
      and temperature that keep tau(alpha) constant. Moreover, tau(beta) is unchanged.
      Thus the three quantities, tau(alpha), tau(beta), and n, are coinvariant to
      changes in pressure and temperature. This strong connection to the alpha
      conductivity relaxation shown by the beta-conductivity relaxation in [Si
      MIm][BF(4)] indicates that it is the analogue of the Johari-Goldstein beta
      relaxation in nonionically conducting glass-formers. The findings have
      fundamental implications on theoretical interpretation of the conductivity
      relaxation processes and glass transition in ionic liquids. It is also the first
      time such a secondary conductivity relaxation or the primitive conductivity
      relaxation of the coupling model has been fully resolved and identified in M"(f)
      in any ionically conducting material that we know of.

PMID- 21950494
TI  - Variant screening of the RHD gene in a large cohort of subjects with D phenotype
      ambiguity: report of 17 novel rare alleles.
AB  - BACKGROUND: A considerable number of RHD alleles responsible for weak and partial
      D phenotypes have been identified over the past decade. Two particular concerns,
      namely, 1) that red blood cells of these phenotypes may cause anti-D immunization
      when transfused to D- recipients and 2) that serologic determination of these
      phenotypes is often doubtful, make genetic analysis of the RHD gene highly
      desirable. STUDY DESIGN AND METHODS: Blood samples that displayed D phenotype
      ambiguity (as determined by serologic analyses) were collected from several sites
      of the Etablissement Francais du Sang and subjected to RHD variant screening by
      means of a previously established denaturing high-performance liquid
      chromatography method followed by direct sequencing. RESULTS: Systematic
      screening of the RHD coding sequences as well as the exon-intron boundaries
      identified DNA variants in 755 of the 806 samples analyzed. In particular, this
      resulted in the identification of 10 novel single-nucleotide substitutions and
      seven novel complex alleles. CONCLUSION: This study further increased the already
      large repertoire of RHD allelic variants. Whereas most of the newly found
      variants are putative weak or partial D alleles, most of the complex alleles are
      readily understandable in the present phylogenetic model of RHD.

PMID- 21950495
TI  - Factors associated with emergency medical services scope of practice for acute
      cardiovascular events.
AB  - OBJECTIVES: To examine prehospital emergency medical services (EMS) scope of
      practice for acute cardiovascular events and characteristics that may affect
      scope of practice; and to describe variations in EMS scope of practice for these
      events and the characteristics associated with that variability. METHODS: In
      2008, we conducted a telephone survey of 1,939 eligible EMS providers in nine
      states to measure EMS agency characteristics, medical director involvement, and
      18 interventions authorized for prehospital care of acute cardiovascular events
      by three levels of emergency medical technician (EMT) personnel. RESULTS: A total
      of 1,292 providers responded to the survey, for a response rate of 67%. EMS scope
      of practice interventions varied by EMT personnel level, with the proportion of
      authorized interventions increasing as expected from EMT-Basic to EMT-Paramedic.
      Seven of eight statistically significant associations indicated that EMS agencies
      in urban settings were less likely to authorize interventions (odds ratios <0.7)
      for any level of EMS personnel. Based on the subset of six statistically
      significant associations, fire department-based EMS agencies were two to three
      times more likely to authorize interventions for EMT-Intermediate personnel.
      Volunteer EMS agencies were more than twice as likely as nonvolunteer agencies to
      authorize interventions for EMT-Basic and EMT-Intermediate personnel but were
      less likely to authorize any one of the 11 interventions for EMT-Paramedics.
      Greater medical director involvement was associated with greater likelihood of
      authorization of seven of the 18 interventions for EMT-Basic and EMT-Paramedic
      personnel but had no association with EMT-Intermediate personnel. CONCLUSIONS: We
      noted statistically significant variations in scope of practice by rural vs.
      urban setting, medical director involvement, and type of EMS service (fire
      department-based/non-fire department-based; volunteer/paid). These variations
      highlight local differences in the composition and capacity of EMS providers and
      offer important information for the transition towards the implementation of a
      national scope of practice model.

PMID- 21950496
TI  - The role of mitochondria in energy production for human sperm motility.
AB  - Mitochondria of spermatozoa are different from the corresponding organelles of
      somatic cells, in both their morphology and biochemistry. The biochemical
      differences are essentially related to the existence of specific enzyme isoforms,
      which are characterized by peculiar kinetic and regulatory properties. As
      mitochondrial energy metabolism is a key factor supporting several sperm
      functions, these organelles host critical metabolic pathways during germ cell
      development and fertilization. Furthermore, spermatozoa can use different
      substrates, and therefore activate different metabolic pathways, depending on the
      available substrates and the physico-chemical conditions in which they operate.
      This versatility is critical to ensure fertilization success. However, the most
      valuable aspect of mitochondria function in all types of cells is the production
      of chemical energy in the form of ATP which can be used, in the case of
      spermatozoa, for sustaining sperm motility. The latter, on the other hand,
      represents one of the major determinants of male fertility. Accordingly, the
      presence of structural and functional alterations in mitochondria from
      asthenozoospermic subjects confirms the important role played by these organelles
      in energy maintenance of sperm motility. The present study gives an overview of
      the current knowledge on the energy-producing metabolic pathways operating inside
      human sperm mitochondria and critically analyse the differences with respect to
      somatic mitochondria. Such a comparison has also been carried out between the
      functional characteristics of human sperm mitochondria and those of other
      mammalian species. A deeper understanding of mitochondrial energy metabolism
      could open up new avenues of investigation in bioenergetics of human sperm
      mitochondria, both in physiological and pathological conditions.

PMID- 21950497
TI  - Three-dimensional morphology of iron oxide nanoparticles with reactive concave
      surfaces. A compressed sensing-electron tomography (CS-ET) approach.
AB  - In this paper, we apply electron tomography (ET) to the study of the three
      dimensional (3D) morphology of iron oxide nanoparticles (NPs) with reactive
      concave surfaces. The ability to determine quantitatively the volume and shape of
      the NP concavity is essential for understanding the key-lock mechanism
      responsible for the destabilization of gold nanocrystals within the iron oxide NP
      concavity. We show that quantitative ET is enhanced greatly by the application of
      compressed sensing (CS) techniques to the tomographic reconstruction. High
      fidelity tomograms using a new CS-ET algorithm reveal with clarity the
      concavities of the particle and enable 3D nanometrology studies to be undertaken
      with confidence. In addition, the robust performance of the CS-ET algorithm with
      undersampled data should allow rapid progress with time-resolved 3D nanoscale
      studies, 3D atomic resolution imaging, and cryo-tomography of nanoscale cellular
      structures.

PMID- 21950498
TI  - Mirror, mirror on the wall...how photodamaged am I?

PMID- 21950499
TI  - Interventions for 'rosacea'.

PMID- 21950500
TI  - Human papillomavirus and squamous cell carcinoma.

PMID- 21950501
TI  - English melanoma by body site: keep wearing the trousers?

PMID- 21950502
TI  - British Association of Dermatologists' guidelines for the safe and effective
      prescribing of azathioprine 2011.

PMID- 21950503
TI  - Antigen-presenting cell marker expression and phagocytotic activity in
      periodontal ligament cells.
AB  - BACKGROUND: Periodontal ligament (PDL) cells are the main cellular constituents
      of the periodontium, maintain the integrity of the connective tissue, and impact
      pathology in periodontitis. The aim of this study was to analyze whether PDL
      cells recognize foreign particles and participate in the immune response to
      periodontal pathogens. METHODS: Expression of surface proteins characteristic of
      antigen-presenting cells (APCs) (major histocompatibility complex [MHC] class II,
      CD40, CD80, CD86) was analyzed in PDL cells after challenge with the cytokines
      interleukin (IL)-1beta, IL-17A, and interferon-gamma (IFN-gamma) or with heat
      killed Aggregatibacter actinomycetemcomitans using real-time PCR and flow
      cytometry. Confocal laser scanning microscopy, transmitted light microscopy, flow
      cytometry, and time-lapse microscopy were applied to analyze their phagocytotic
      capacity of collagen (carboxylate-modified microspheres), non-periodontal
      (Escherichia coli) and periodontal (Aggregatibacter actinomycetemcomitans)
      pathogens. Furthermore, it was examined whether cytokine activation of PDL cells
      affects the phagocytosis of collagen or bacteria. RESULTS: PDL cells upregulated
      MHC class II after cytokine stimulation on transcriptional level, whereas co
      stimulatory molecules characteristic of professional APCs were not induced.
      Analyses on protein level revealed that MHC class II was not constitutively
      expressed in all PDL cell lines used. PDL cells phagocytosed both collagen and
      bacteria via acidic vesicles, suggesting the formation of phagosomes.
      Phagocytosis could be partially inhibited by inhibitors of phagocytosis, i.e.,
      dynasore and wortmannin. Pre-incubation with cytokines did not further enhance
      the phagocytosis rate of collagen or bacteria. CONCLUSIONS: These results suggest
      that PDL cells do not only represent bystanders in periodontal infections, but
      display non-professional APC characteristics, suggesting possible participation
      in immune reactions of the oral cavity.

PMID- 21950510
TI  - Preparation of optically pure alpha-trifluoromethyl-alpha-amino acids from N
      tosyl-2-trifluoromethyl-2-alkyloxycarbonyl aziridine.
AB  - The preparation of optically pure alpha-trifluoromethyl-alpha-amino acids from N
      tosyl-2-trifluoromethyl-2-alkyloxycarbonylaziridine is described. Optically pure
      aziridine was prepared with a 60% yield via three steps from optically pure 2,3
      epoxy-1,1,1-trifluoropropane (TFPO). Ring-opening reactions of the aziridine with
      a variety of nucleophiles and subsequent deprotection of the N-tosyl moieties
      gave the optically pure beta-substituted-alpha-trifluoromethyl-alpha-amino acids
      in moderate to good yields (up to 85%) without racemization at the quaternary
      stereogenic center of the amino acid.

PMID- 21950511
TI  - Disruption of barrier function in dermatophytosis and pityriasis versicolor.
AB  - Dermatophytes have the ability to form molecular attachments to keratin and use
      it as a source of nutrients, colonizing keratinized tissues, including the
      stratum corneum of the skin. Malassezia species also affect the stratum corneum
      of the skin. Therefore, dermatophytosis and pityriasis versicolor of the skin are
      thought to be important factors of profound changes in skin barrier structure and
      function. We aimed to describe the changes in transepidermal water loss (TEWL),
      stratum corneum hydration, and skin pH in the lesions of the dermatophytosis and
      pityriasis versicolor. Thirty-six patients with dermatophytosis (14 with tinea
      cruris, 13 with tinea corporis and nine with tinea pedis or tinea manus) and 11
      patients with pityriasis versicolor were included in this study. TEWL, stratum
      corneum conductance and skin pH were determined by biophysical methods to examine
      whether our patients exhibited changes in barrier function. Dermatophytosis and
      pityriasis versicolor except tinea pedis and tinea manus showed highly
      significant increase in TEWL compared with adjacent infection-free skin.
      Hydration was significantly reduced in lesional skin compared with adjacent
      infection-free skin. From this study, infections with dermatophytes and
      Malassezia species on the body can alter biophysical properties of the skin,
      especially the function of stratum corneum as a barrier to water loss. On the
      contrary, infections with dermatophytes on the palms and soles little affect the
      barrier function of the skin.

PMID- 21950513
TI  - Study of sociodemographic variables linked to lifestyle and their possible
      influence on cognitive reserve.
AB  - Cognitive reserve is an active mechanism based on the application of resources
      learned thanks to a good education, profession, or premorbid intelligence. The
      aim of this research is to study whether the inclusion of sociodemographic
      variables linked to lifestyle can discriminate individuals more effectively
      regarding their level of cognitive reserve. Results show the importance of
      educational, intellectual, and professional type variables, which can contribute
      to a deeper knowledge of this construct. In our view, a broad number of variables
      should be used to assess cognitive reserve effectively.

PMID- 21950514
TI  - Effect of chronic sleep restriction on sleepiness and working memory in
      adolescents and young adults.
AB  - OBJECTIVES: To test the feasibility of using a home-based sleep restriction
      protocol in adolescents and young adults; and to examine the different effects of
      chronic sleep restriction on a subjective sleepiness scale and working memory
      task in adolescents and young adults. METHOD: Twenty adolescents (ages 13-16
      years) and 20 young adults (ages 18-20 years) underwent a 2-week home-based sleep
      manipulation protocol consisting of a week of 5 school days with 8 hr spent in
      bed per night and another week of 5 school days with 6 hr spent in bed per night.
      The protocol used a counterbalanced crossover experimental design. Subjective
      sleepiness was scored by the participant each morning, and working memory tests
      were administered during the weekend corresponding to each experimental week.
      RESULTS: Adherence to the prescribed protocol was similar in the two groups, and
      both groups achieved the desired differences in total sleep duration across the
      two sleep conditions. Subjective sleepiness scores significantly increased in
      young adults after sleep restriction, but were not accompanied by significant
      changes in working memory. However, reaction times during simple verbal and
      arithmetic working memory tasks increased among adolescents after sleep
      restriction, without affecting accuracy on task, and without eliciting increases
      in subjective sleepiness scores. CONCLUSION: Mild sleep restriction for 5 days
      impairs reaction times during working memory tasks in adolescents in the absence
      of increased perception of sleepiness.

PMID- 21950512
TI  - Relationship of ethnicity, age, education, and reading level to speed and
      executive function among HIV+ and HIV- women: the Women's Interagency HIV Study
      (WIHS) Neurocognitive Substudy.
AB  - Use of neuropsychological tests to identify HIV-associated neurocognitive
      dysfunction must involve normative standards that are well suited to the
      population of interest. Norms should be based on a population of HIV-uninfected
      individuals as closely matched to the HIV-infected group as possible and must
      include examination of the potential effects of demographic factors on test
      performance. This is the first study to determine the normal range of scores on
      measures of psychomotor speed and executive function among a large group of
      ethnically and educationally diverse HIV-uninfected, high-risk women, as well as
      their HIV-infected counterparts. Participants (n = 1,653) were administered the
      Trail Making Test Parts A and B (Trails A and Trails B), the Symbol Digit
      Modalities Test (SDMT), and the Wide Range Achievement Test-3 (WRAT-3). Among HIV
      uninfected women, race/ethnicity accounted for almost 5% of the variance in
      cognitive test performance. The proportions ofvariance in cognitive test
      performance accounted for by age (13.8%), years of school (4.1%), and WRAT-3
      score (11.5%) were each significant, but did not completely account for the
      effect of race (3%). HIV-infected women obtained lower scores than HIV-uninfected
      women on time to complete Trails A and B, SDMT total correct, and SDMT incidental
      recall score, but after adjustment for age, years of education, racial/ethnic
      classification, and reading level, only the difference on SDMT total correct
      remained significant. Results highlight the need to adjust for demographic
      variables when diagnosing cognitive impairment in HIV-infected women. Advantages
      of demographically adjusted regression equations developed using data from HIV
      uninfected women are discussed.

PMID- 21950516
TI  - Commentary: the how and what of the WHO aims of extending CAMH services in
      developing countries: a response to Morris et al. (2011).

PMID- 21950515
TI  - Correlates of quitting the Paced Auditory Serial Addition Test in cognitively
      normal older adults participating in a study of normal cognitive aging.
AB  - Our study of cognitive aging involves a comprehensive battery of
      neuropsychological measures. The Paced Auditory Serial Addition Test (PASAT) is
      the only test that some of our participants will refuse to complete. We explored
      variables related to quitting versus completing the PASAT in this sample of
      normal older adults. We hypothesized that quitting would be related to
      personality features, subclinical anxiety symptoms, demographics, and/or Wechsler
      Adult Intelligence Scale-Revised (WAIS-R) Arithmetic performance. A logistical
      regression model including NEO Personality Inventory-Revised (NEO-PI-R)
      depression and excitement seeking, age, and WAIS-R Arithmetic classified
      participants with moderate accuracy. We encourage investigators involved in
      longitudinal studies to consider causes for missing data, especially when
      secondary to participant refusal.

PMID- 21950517
TI  - Cognitive and psychiatric phenotypes of movement disorders in children: a
      systematic review.
AB  - AIM: The cognitive and psychiatric aspects of adult movement disorders are well
      established, but specific behavioural profiles for paediatric movement disorders
      have not been delineated. Knowledge of non-motor phenotypes may guide treatment
      and determine which symptoms are suggestive of a specific movement disorder and
      which indicate medication effects. METHOD: The goal of this review is to outline
      the known cognitive and psychiatric symptoms associated with paediatric movement
      disorders. We used a systematic approach, via PubMed, and reviewed over 400
      abstracts of studies of selected disorders, of which 88 papers reporting
      paediatric non-motor symptoms are summarized. RESULTS: Obsessive-compulsive
      disorder was manifest in children with paediatric autoimmune neuropsychiatric
      disorders associated with streptococcal infections and Sydenham chorea. Children
      with opsoclonus-myoclonus syndrome had, for the most part, cognitive and
      behavioural problems, and attention-deficit-hyperactivity disorder was reported
      as a major comorbidity in Tourette syndrome, stereotypies, and restless legs
      syndrome. Symptoms of depression and anxiety were more frequent in individuals
      with idiopathic dystonia. Affective disorders were suggestive of Wilson disease.
      Cognitive decline was common in children with juvenile Huntington disease. A
      limitation of this review was the lack of systematic assessment in paediatric
      movement disorders for evaluation and uniform definitions. INTERPRETATION:
      Although the literature in non-motor phenomena is still emerging, recognition of
      salient cognitive and psychiatric phenomena may facilitate management of
      paediatric movement disorders.

PMID- 21950518
TI  - Effect of vitrification of feline ovarian cortex on follicular and oocyte quality
      and competence.
AB  - Cryopreservation of ovarian cortex has important implications in the preservation
      of fertility and biodiversity in animal species. Slow freezing of cat ovarian
      tissue resulted in the preservation of follicular morphology and in the
      follicular development after xenografting. Vitrification has been recently
      applied to ovarian tissues of different species, but no information is available
      on the effect of this method on feline ovarian cortex. Moreover, meiotic
      competence of fully grown oocytes isolated from cryopreserved tissue has not been
      reported. The aim of this study was to evaluate the effect of vitrification of
      feline ovarian cortex on follicular morphology and oocyte integrity, as well as
      meiotic competence. A total of 352 fragments (1.5-2 mm(3) ) were obtained from
      ovarian cortical tissues: 176 were vitrified and 176 were used fresh as control.
      Histological evaluation of fresh and vitrified fragments showed intact follicles
      after cryopreservation procedures with no statistically significant destructive
      effect from primordial to antral follicles. After IVM, oocytes collected from
      vitrified ovarian fragment showed a higher proportion of gametes arrested at
      germinal vesicle (GV) stage compared to those isolated from fresh control tissue
      (33.8% vs 2.9%; p < 0.001). However, oocytes isolated from vitrified tissues were
      able to resume meiosis, albeit at lower rate than those collected from fresh
      tissues (39.8% vs 85.9%; p < 0.00001). Vitrification induced changes in the
      organization of cytoskeletal elements (actin microfilaments and microtubules) of
      oocytes, but significantly only for actin network (p < 0.001). Finally, chromatin
      configuration within the GV was not affected by the cryopreservation procedure.
      Our study demonstrated that vitrification preserves the integrity of ovarian
      follicles and that oocytes retrieved from cryopreserved tissue maintain the
      capability of resuming meiosis. To our knowledge, this has not previously been
      reported in the cat.

PMID- 21950520
TI  - Synthesis and evaluation of a series of 1,2,4,5-tetrazines for bioorthogonal
      conjugation.
AB  - 1,2,4,5-Tetrazines have been established as effective dienes for inverse electron
      demand [4 + 2] Diels-Alder cycloaddition reactions with strained alkenes for over
      50 years. Recently, this reaction pair combination has been applied to
      bioorthogonal labeling and cell detection applications; however, to date, there
      has been no detailed examination and optimization of tetrazines for use in
      biological experiments. Here, we report the synthesis and characterization of 12
      conjugatable tetrazines. The tetrazines were all synthesized in a similar fashion
      and were screened in parallel to identify candidates most ideally suited for
      biological studies. In depth follow-up studies revealed compounds with varying
      degrees of stability and reactivity that could each be useful in different
      bioorthogonal applications. One promising, highly stable, and water-soluble
      derivative was used in pretargeted cancer cell labeling studies, confirming its
      utility as a bioorthogonal moiety.

PMID- 21950521
TI  - Elimination of bacteria from human semen during sperm preparation using density
      gradient centrifugation with a novel tube insert.
AB  - The occurrence of bacteria in sperm samples intended for in vitro fertilisation
      can compromise the outcome of assisted reproductive techniques. Effective semen
      processing procedures should therefore be implemented to remove bacteria from
      semen. Unfortunately, technique failure does occur whereby bacteria can be found
      in processed sperm preparations. To improve the effectiveness of semen
      processing, a novel centrifuge tube insert was developed to facilitate the
      layering of density gradients and semen, and to prohibit the re-infection of
      purified sperm pellets. The purpose of this study was to: (i) determine the
      prevalence and type of bacteria present in semen of patients participating in the
      Unit's assisted reproduction program and (ii) evaluate the effectiveness of
      density gradient centrifugation with the novel tube insert, for the elimination
      of bacteria and yeast from spiked human semen samples. A survey in 2007-2010
      indicated that 50% of semen samples were found to have positive bacterial
      cultures. Semen processing by means of density gradient centrifugation with the
      novel tube insert eliminated significantly more in vitro derived (spiked)
      bacteria and yeast from semen compared to processing without the insert (P <
      0.004). Therefore, it is highly recommended that the centrifuge tube insert,
      ProInsertTM, be incorporated into assisted reproductive programs.

PMID- 21950522
TI  - Attitudes to and knowledge about oral health care among nursing home personnel-
      an area in need of improvement.
AB  - BACKGROUND: In 1999, a dental reform became law in Sweden that regulated both
      dental care to dependent individuals and training in oral health care for nursing
      home personnel. Substantial resources have been channelled into these efforts,
      but the outcome of these efforts has not been evaluated. The aim of this study
      was to explore attitudes to and knowledge about oral health care among nursing
      home personnel more than 5 years after the law was adopted, that being 2005.
      METHODS: A total of 454 individuals employed at nursing homes answered a
      questionnaire of 16 multiple-choice items concerning attitudes to and knowledge
      about oral health care. RESULTS: Eighty-nine per cent considered oral health care
      to be an important part of good nursing. The answers indicated problems, however,
      when it came to its implementation and knowledge, and 35% stated that they had
      had no formal education in oral health care. CONCLUSIONS: Despite generally
      positive oral health care attitudes, it is important that oral health care
      education is available to and made of interest for all nursing home personnel,
      especially in light of the increase in number of natural teeth and frequency of
      crowns and bridges among dependent elderly.

PMID- 21950525
TI  - Apheresis-related enrichment of CD26++ T lymphocytes: phenotypic characterization
      and correlation with unfavorable outcome in autologous hematopoietic progenitor
      cell transplantation.
AB  - BACKGROUND: The lymphocyte surface glycoprotein CD26 anchors adenosine deaminase
      to the lymphocyte surface and possesses dipeptidyl peptidase IV activity. A
      distinct subset of CD26++ lymphocytes in autologous hematopoietic progenitor cell
      transplants (HPCTs) was investigated with regard to clinical outcome after
      autologous HPCT. The phenotype of these cells was characterized in more detail.
      STUDY DESIGN AND METHODS: Forty-two eligible patients (multiple myeloma, n = 31;
      Hodgkin's disease, n = 3; non-Hodgkin's lymphoma, n = 6; peripheral
      neuroectodermal tumor, n = 1; acute myeloid leukemia, n = 1) were included in a
      retrospective analysis. Distinct cellular subsets, including CD26+/- and CD26++
      subpopulations, were analyzed for correlations with kinetics of engraftment,
      progression-free survival, and overall survival. RESULTS: The numbers of CD26++ T
      lymphocytes in the autograft correlated inversely with progression-free survival
      (p = 0.013). CD26++ T lymphocytes transfused per kg of body weight were
      predictive for the occurrence of disease progression or relapse (p = 0.006).
      Importantly, the numbers of CD26++ cells showed a highly variable degree of
      enrichment in the autograft, but no significant variations in the peripheral
      blood before apheresis. The characterization of CD26++ cells revealed that
      CD26++/CD8+ cells form a homogeneous population with a distinct T memory cell
      phenotype (CD45RO+, CD161++, interleukin-18Ralpha++, CCR7-). CONCLUSION: CD26++
      lymphocytes define a discrete phenotype of T memory cells with known
      chemoresistance and T-cell-repopulating capacity. Their enrichment during
      apheresis and corresponding depletion from the circulation are associated with an
      adverse outcome in autologous HPCT.

PMID- 21950524
TI  - Ursolic acid induces apoptosis in human leukaemia cells and exhibits anti
      leukaemic activity in nude mice through the PKB pathway.
AB  - BACKGROUND AND PURPOSE: Ursolic acid (UA) has been extensively used as an anti
      leukaemic agent in traditional Chinese medicine. In the present study, we
      investigated the ability of UA to induce apoptosis in human leukaemia cells in
      relation to its effects on caspase activation, Mcl-1 down-regulation and
      perturbations in stress-induced signalling pathways such as PKB and JNK.
      EXPERIMENTAL APPROACH: Leukaemia cells were treated with UA after which
      apoptosis, caspase activation, PKB and JNK signalling pathways were evaluated.
      The anti-tumour activity of UA was evaluated using xenograft mouse model. KEY
      RESULTS: UA induced apoptosis in human leukaemia cells in a dose- and time
      dependent manner; this was associated with caspase activation, down-regulation of
      Mcl-1 and inactivation of PKB accompanied by activation of JNK. Enforced
      activation of PKB by a constitutively active PKB construct prevented UA-mediated
      JNK activation, Mcl-1 down-regulation, caspase activation and apoptosis.
      Conversely, UA lethality was potentiated by the PI3-kinase inhibitor LY294002.
      Interruption of the JNK pathway by pharmacological or genetic (e.g. siRNA)
      attenuated UA-induced apoptosis. Furthermore, UA-mediated inhibition of tumour
      growth in vivo was associated with induction of apoptosis, inactivation of PKB as
      well as activation of JNK. CONCLUSIONS AND IMPLICATIONS: Collectively, these
      findings suggest a hierarchical model of UA-induced apoptosis in human leukaemia
      cells in which UA induces PKB inactivation, leading to JNK activation and
      culminating in Mcl-1 down-regulation, caspase activation and apoptosis. These
      findings indicate that interruption of PKB/JNK pathways may represent a novel
      therapeutic strategy in haematological malignancies.

PMID- 21950526
TI  - Mercury emissions from biomass burning in China.
AB  - Biomass burning covers open fires (forest and grassland fires, crop residue
      burning in fields, etc.) and biofuel combustion (crop residues and wood, etc.,
      used as fuel). As a large agricultural country, China may produce large
      quantities of mercury emissions from biomass burning. A new mercury emission
      inventory in China is needed because previous studies reflected outdated biomass
      burning with coarse resolution. Moreover, these studies often adopted the
      emission factors (mass of emitted species per mass of biomass burned) measured in
      North America. In this study, the mercury emissions from biomass burning in China
      (excluding small islands in the South China Sea) were estimated, using recently
      measured mercury concentrations in various biomes in China as emission factors.
      Emissions from crop residues and fuelwood were estimated based on annual reports
      distributed by provincial government. Emissions from forest and grassland fires
      were calculated by combining moderate resolution imaging spectroradiometer
      (MODIS) burned area product with combustion efficiency (ratio of fuel consumption
      to total available fuels) considering fuel moisture. The average annual emission
      from biomass burning was 27 (range from 15.1 to 39.9) Mg/year. This inventory has
      high spatial resolution (1 km) and covers a long period (2000-2007), making it
      useful for air quality modeling.

PMID- 21950527
TI  - The development of the Coalition for Oral Health for the Aging.

PMID- 21950528
TI  - Sugar consumption and preference among Mexican, Chinese, and Nigerian immigrants
      to Texas.
AB  - This pilot study investigated the relationship between sugar consumption/
      preference and the length of residence in the U.S. among certain immigrant
      groups. The study sample consisted of 213 volunteers from community organizations
      and church groups, of Nigerian (45%), Mexican (31%), and Chinese (24%) descent.
      Data were collected on demographics, sugar consumption/preference (24-hour
      dietary recall), and oral health status. The age of respondents varied from 18 to
      93 years with a mean age of 37.0 +/- 11.7 years. The mean length of residence was
      9.2 +/- 7.2 years, and the mean sugar consumption was 122.4 +/- 114.6 g/day.
      Immigrants from Mexico and Nigeria reported consuming more servings of sweets per
      day than the Chinese (p= .006); Mexican immigrants had the highest level of sugar
      preference (p= .001). No significant differences were observed between the length
      of residence and either sugar consumption or sugar preference. Greater
      availability of sugar and sweet snacks does not always result in increased sugar
      consumption or sugar preference.

PMID- 21950529
TI  - Accidental aspiration in a patient with Parkinson's disease during implant
      supported prosthesis construction: a case report.
AB  - This article reports on a case history of an elderly patient with Parkinson's
      disease (PD) who sought treatment at a private dental office. His chief complaint
      was "difficulty in eating due to an illfitting prosthesis." Laboratory tests and
      oral radiographs were made. The surgical placement of an implant was done and,
      subsequently, an implant-supported prosthesis was fitted for the patient. During
      the impression for the construction of the implant-supported prosthesis, the
      patient accidentally aspirated the implant screwdriver. The object was found in
      the lower right lobe of the bronchus, and its removal was necessary in a hospital
      using bronchoscopy under general anesthesia. Patients with PD are considered at
      risk of aspirating and/or ingesting dental instruments. Short treatment periods
      are recommended, preferably during the morning, when the medication prescribed
      for PD is most effective. When treating patients who have a risk for aspirating
      and ingesting small objects, it is important to treat them in a more vertical
      position, and small-sized objects should be secured with dental floss to aid
      retrieval.

PMID- 21950530
TI  - National estimates of the characteristics of individuals infected with HIV who
      are likely to report and receive treatment for painful bleeding gums.
AB  - Painful bleeding gums may be associated with HIV infection. This study examined
      the characteristics of persons reporting the symptom "painful bleeding gums" and
      their likelihood of accessing care. The study population consisted of persons
      receiving care for HIV as part of the HIV Cost and Services Utilization Study
      (HCSUS). In this national population, 5.3% reported painful bleeding gums.
      Significant differences in reporting painful bleeding gums were found between
      Hispanics/Whites, oral health status, and presence of other symptoms. Compared to
      younger persons, those in the middle age group were more likely to seek
      treatment, while persons with the highest CD4 counts were more likely to seek
      treatment than those with the lowest CD4 counts. This study showed that reporting
      painful bleeding gums was a function of ethnicity, other symptoms, and perceived
      oral health, while seeking treatment for painful bleeding gums was related to age
      and CD4 counts. Dentists and other health care providers can have an active role
      in improving the quality of life of persons living with HIV by being aware of the
      relationships that exist between patients with HIV and painful bleeding gums.

PMID- 21950531
TI  - Parents' perspectives on a dental home for children with special health care
      needs.
AB  - The authors surveyed parent-leaders about aspects of a dental home for children
      with special health care needs (CSHCN). State leaders in two advocacy groups
      completed the survey; the response rate was 70.6% of all states. Two of the most
      highly rated aspects of a dental home, endorsed as "essential" by 89% of
      respondents, pertained to dentist-parent interactions: the dentist listens
      carefully to the family, and the dentist helps the family feel like a partner in
      treatment decisions. Likewise, 89% said it was essential that insurance coverage
      allows the child to see needed providers. Dentists' lack of knowledge or
      willingness to treat CSHCN and refusal of Medicaid insurance coverage were
      identified as major barriers to care. More than 84% of respondents reported that
      parents were unaware of the recommendation to establish dental care by 1 year of
      age. Establishing policy and educational strategies should help parents meet this
      dental health goal.

PMID- 21950532
TI  - Caries and periodontal disease in patients with Parkinson's disease.
AB  - Parkinson's disease (PD) has been associated with aging, reduced fine motor
      skills, and malnutrition caused by eating soft sticky foods and a decreased
      liquid intake, which may contribute to the onset of caries, periodontal disease,
      and tooth loss. The objective of this study was to investigate the oral health of
      101 patients with PD (mean age: 66.2 +/- 10.5 years) and compare them to 75
      control subjects (CO) (mean age 71 +/- 10.53). Patients with PD had poorer oral
      health than the control group (papilla bleeding index: PD 6.97 +/- 8.34; CO 2.12
      +/- 2.73). Lower frequencies of daily toothbrushing (PD: 1.69 +/- 0.83; CO: 2.08
      +/- 0.80), longer time since the last dentist visit (PD: 1.94 +/- 1.49; CO: 1.21
      +/- 0.60 years), and reduced salivary flow (PD: 2.69 +/- 0.94; CO: 3.53 +/- 1.11
      ml). All of these factors may be related to the gingival recession and tooth
      mobility found in our patients with PD. Individuals with PD, their caregivers,
      and their physicians need to focus more on their oral health and quality of oral
      hygiene.

PMID- 21950533
TI  - Distraction osteogenesis in the maxilla for a patient with a repaired cleft lip
      and palate: a case report.
AB  - Distraction osteogenesis (DO) has gained wide acceptance as a viable modality for
      lengthening hypoplastic skeletal structures in the maxillofacial region. For
      patients with cleft lip and palate with skeletal maxillary deficiency, this
      technique has recently been applied extensively as an alternative to orthognathic
      surgical procedures. Decreased intraoperative morbidity and rates of
      postoperative midface regression along with esthetically acceptable soft tissue
      profile are the main advantages of this procedure against traditional
      osteotomies. This case report documents the use of rigid external distraction
      (RED) in the treatment of a 20-year-old female patient with midface deficiency
      secondary to cleft lip and palate repair.

PMID- 21950537
TI  - Insulin modulates inflammatory and repair responses to elastase-induced emphysema
      in diabetic rats.
AB  - As pulmonary emphysema and diabetes mellitus are common diseases, concomitance of
      both is correspondingly expected to occur frequently. To examine whether insulin
      influences the development of inflammation in the alveolar septa, diabetic male
      Wistar rats (alloxan, 42 mg/kg, i.v., n = 37) and matching controls (n = 31) were
      used. Ten days after alloxan injection, diabetic and control rats were instilled
      with physiologic saline solution containing porcine pancreatic elastase (PPE,
      0.25 IU/0.2 ml, right lung) or saline only (left lung). The following analyses
      were performed: (i) number of leucocytes in the bronchoalveolar lavage (BAL)
      fluid of the animals, 6 h after PPE/saline instillation (early time point); and
      (ii) mean alveolar diameter (MUm) and quantification of elastic and collagen
      fibres (%) 50 days after PPE/saline instillation (late time point). Relative to
      controls, alloxan-induced diabetic rats showed a 42% reduction in the number of
      neutrophils in BAL fluid, a 20% increase in the mean alveolar diameter and a 33%
      decrease in elastic fibre density in the alveolar septa. Treatment of diabetic
      rats with 4 IU neutral protamine Hagedorn (NPH) insulin, 2 h before elastase
      instillation, restored the number of neutrophils in the BAL fluid. The mean
      alveolar diameter and elastic fibre content in alveolar septa matched the values
      observed in control rats if diabetic rats were treated with 4 IU NPH insulin 2 h
      before instillation followed by 2 IU/day for the next 50 days. Density of
      collagen fibres did not differ between the various groups. Thus, the data
      presented suggest that insulin modulates the inflammatory and repair responses in
      elastase-induced emphysema, and assures normal repair and tissue remodelling.

PMID- 21950539
TI  - Finely tailored performance of inverted organic photovoltaics through layer-by
      layer interfacial engineering.
AB  - Control over interfacial properties in organic photovoltaics (OPVs) is critical
      for many aspects of their performance. Functionalization of the transparent
      conducting electrode, in this case, indium tin oxide (ITO), through an
      electrostatic layer by layer (eLbL) approach with cationic N,N'-bis[2
      (trimethylammonium)ethylene] perylene-3,4,9,10-tetracarboxyldiimide (PTCDI(+))
      and anionic poly(3,4-ethylenedioxythiophene):poly(p-styrenesulfonate) (PEDOT:PSS(
      )), led to high control over the surface properties. The films were studied
      through a variety of surface and spectroscopic techniques, including X-ray
      photoelectron spectroscopy (XPS), UV-visible spectroscopy, atomic force
      microscopy (AFM), and ellipsometry. The work function of modified ITO was
      measured by UV photoelectron spectroscopy (UPS) and showed oscillating values
      with respect to odd-even layer numbers; the strong odd-even effect is due to the
      differing electronic characteristics of the top layer, either PTCDI(+) or
      PEDOT:PSS(-). The modified ITO electrodes were then used as the cathode in a
      series of inverted organic photovoltaic architectures. The performance of
      inverted OPVs was, in parallel to the UPS results, found to be highly dependent
      on the layer number of coated films and showed an obvious oscillation based on
      layer number. Inverted OPVs were retested after 128 days of storage in air, and
      almost all devices maintained over 70% of original power conversion efficiency
      (PCE).

PMID- 21950538
TI  - Toward evidence-based practice in acne: consensus of an Asian Working Group.
AB  - Acne vulgaris is common throughout the world and often perceived by both patients
      and clinicians as an inconsequential disease of adolescence. In reality, however,
      acne is a chronic medical disease that lasts for years and causes a considerable
      impact on quality of life. Many patients with acne experience emotional problems
      due to their disease, which can lead to reduced social interactions and even a
      lower likelihood of employment. Little has been written specifically about acne
      in Asian patients in the English-language medical published work, perhaps due to
      an assumption that the management of acne is the same in all populations. A group
      of acne experts from nine Asian countries and the USA met to review and discuss
      acne care within the Asia-Pacific region, focusing on evidence-based medicine.
      This group developed a care algorithm using results of clinical trials as well as
      knowledge of practice patterns.

PMID- 21950540
TI  - The nature of the sodium dodecylsulfate micellar pseudophase as studied by
      reaction kinetics.
AB  - The nature of the rate-retarding effects of anionic micelles of sodium dodecyl
      sulfate (SDS) on the water-catalyzed hydrolysis of a series of substituted 1
      benzoyl-1,2,4-triazoles (1a-f) has been studied. We show that medium effects in
      the micellar Stern region of SDS can be reproduced by simple aqueous model
      solutions containing small-molecule mimics for the surfactant headgroups and
      tails, namely sodium methyl sulfate (NMS) and 1-propanol, in line with our
      previous kinetic studies for cationic surfactants (     Buurma et al.   J. Org.
      Chem.     2004  ,   69  ,   3899 - 3906  ). We have improved our mathematical
      description leading to the model solution, which has made the identification of
      appropriate model solutions more efficient. For the Stern region of SDS, the
      model solution consists of a mixture of 35.3 mol dm(-3) H(2)O, corresponding to
      an effective water concentration of 37.0 mol dm(-3), 3.5 mol dm(-3) sodium
      methylsulfate (NMS) mimicking the SDS headgroups, and 1.8 mol dm(-3) 1-propanol
      mimicking the backfolding hydrophobic tails. This model solution quantitatively
      reproduces the rate-retarding effects of SDS micelles found for the hydrolytic
      probes 1a-f. In addition, the model solution accurately predicts the
      micropolarity of the micellar Stern region as reported by the E(T)(30)
      solvatochromic probe. The model solution also allows the separation of the
      individual contributions of local water concentration (water activity), polarity
      and hydrophobic interactions, ionic strength and ionic interactions, and local
      charge to the observed local medium effects. For all of our hydrolytic probes,
      the dominant rate-retarding effect is caused by interactions with the surfactant
      headgroups, whereas the local polarity as reported by the solvatochromic E(T)(30)
      probe and the Hammett rho value for hydrolysis of 1a-f in the Stern region of SDS
      micelles is mainly the result of interactions with the hydrophobic surfactant
      tails. Our results indicate that both a mimic for the surfactant tails (NMS) and
      a mimic for the surfactant headgroups (1-propanol) are required in a model
      solution for the micellar pseudophase to reproduce all medium effects experienced
      by a variety of different probes.

PMID- 21950541
TI  - Intrapartum epidural analgesia and ST analysis of the fetal electrocardiogram.
AB  - OBJECTIVE: To evaluate the influence of intrapartum epidural analgesia on the
      occurrence of ST events of the fetal ECG. DESIGN: Nested case-control study.
      SETTING: Single-centre academic hospital in the Netherlands. POPULATION: Laboring
      women with a high-risk singleton pregnancy in cephalic position beyond 36 weeks
      of gestation. METHODS: Data of 72 women who received epidural analgesia using
      bupivacaine combined with sufentanil and 72 control women were collected and
      analyzed. The moment of epidural infusion was defined as t(0) . In the control
      group, t(0) was defined by matching dilatation in centimeters. STAN registrations
      from one hour before until two hours after t(0) were classified, and the numbers
      and types of ST events were recorded and judged according to the STAN clinical
      guidelines. T/QRS ratios were collected from one hour before t(0) until two hours
      after t(0) , and differences were compared between the two groups. MAIN OUTCOME
      MEASURES: Numbers and types of ST events and mean T/QRS ratios before and after
      t(0). RESULTS: There were no significant differences between cases and control
      women regarding the numbers of ST events, types of ST events and whether they
      were significant (intervention advised) or not. Correction for outliers (three
      cases and three control women) did not change the results. Differences of T/QRS
      ratios before and after t(0) were comparable between cases and control women.
      CONCLUSIONS: Epidural analgesia has no effect on the numbers or types of ST
      events when using ST analysis of the fetal ECG.

PMID- 21950542
TI  - Evaluation of three methods for retrospective correction of vignetting on medical
      microscopy images utilizing two open source software tools.
AB  - Correction of vignetting on images obtained by a digital camera mounted on a
      microscope is essential before applying image analysis. The aim of this study is
      to evaluate three methods for retrospective correction of vignetting on medical
      microscopy images and compare them with a prospective correction method. One
      digital image from four different tissues was used and a vignetting effect was
      applied on each of these images. The resulted vignetted image was replicated four
      times and in each replica a different method for vignetting correction was
      applied with fiji and gimp software tools. The highest peak signal-to-noise ratio
      from the comparison of each method to the original image was obtained from the
      prospective method in all tissues. The morphological filtering method provided
      the highest peak signal-to-noise ratio value amongst the retrospective methods.
      The prospective method is suggested as the method of choice for correction of
      vignetting and if it is not applicable, then the morphological filtering may be
      suggested as the retrospective alternative method.

PMID- 21950544
TI  - Glycolic acid chemical peeling improves inflammatory acne eruptions through its
      inhibitory and bactericidal effects on Propionibacterium acnes.
AB  - Glycolic acid chemical peeling is effective for treating comedones, and some
      clinical data show that it also improves inflammatory eruptions. The purpose of
      this study was to identify the mechanism of glycolic acid chemical peeling to
      improve inflammatory acne. To assess growth inhibitory and bactericidal effects
      of glycolic acid on Propionibacterium acnes in vitro, we used an agar diffusion
      method and a time-kill method. To reveal bactericidal effects in vivo, we
      established an agar-attached method which correlated well with the ordinary swab
      wash method, and we used the agar-attached method to compare the numbers of
      propionibacteria on the cheek treated with glycolic acid chemical peeling. Our
      results show that 30% glycolic acid (at pH 1.5, 3.5 and 5.5) formed growth
      inhibitory circles in the agar diffusion method, but the diameters of those
      circles were smaller than with 1% nadifloxacin lotion or 1% clindamycin gel. In
      the time-kill method, 30% glycolic acid (at pH 1.5 and 3.5) or 1% nadifloxacin
      lotion reduced the number of P. acnes to less than 100 CFU/mL within 5 min. In
      contrast, in 30% glycolic acid (at pH 5.5) or in 1% clindamycin gel, P. acnes
      survived for more than 4 h. Chemical peeling with 35% glycolic acid (at pH 1.2)
      decreased the number of propionibacteria on the cheeks of patients compared with
      untreated controls (P < 0.01). Our results demonstrate that glycolic acid has
      moderate growth inhibitory and bactericidal effects on P. acnes, and that
      chemical peeling with glycolic acid works on inflammatory acne via those effects.

PMID- 21950543
TI  - Effectiveness of antioxidants (propolis, blueberry, vitamin E) associated with
      verapamil in the medical management of Peyronie's disease: a study of 151 cases.
AB  - A total of 151 patients (age: 24-74 years, mean: 55 +/- 10.3) diagnosed with
      Peyronie's disease were enrolled in a non-surgical treatment. In addition to
      medical histories and physical examinations, all patients underwent the following
      tests: penile ultrasound, IIEF questionnaire and photographic documentation. The
      penile curvature was measured by taking a photograph during maximum erection. All
      151 patients were treated at different times and with different combinations of
      drugs, and afterwards, they were clinically studied and divided into five
      different treatment groups: 1st = verapamil (injection + iontophoresis) + vitamin
      E + topical diclofenac + blueberries; 2nd = verapamil (injection + iontophoresis)
      + vitamin E + topical diclofenac + propolis; 3rd = verapamil (injection) +
      vitamin E + topical Diclofenac; 4th = verapamil (iontophoresis) + vitamin E +
      topical diclofenac; 5th = verapamil (injection + iontophoresis) + topical
      diclofenac + blueberries + propolis. All patients were treated for 6 months after
      which they underwent the same follow-up tests as performed prior to the
      treatment. The following was achieved: group 1 had the most reduction in plaque
      size (-66.4%; p = 0.000), group 2 obtained the highest rate where penile
      curvature disappeared (24.5%; p = 0.019); the best results with reference to
      decrease in curvature angle were reached by the 2nd group (-14 degrees ) and
      group 1 obtained -9.6 degrees  (p = 0.000).

PMID- 21950547
TI  - Sound and vibration: effects on infants' heart rate and heart rate variability
      during neonatal transport.
AB  - AIM: To measure the effect of sound and whole-body vibration on infants' heart
      rate and heart rate variability during ground and air ambulance transport.
      METHODS: Sixteen infants were transported by air ambulance with ground ambulance
      transport to and from the airports. Whole-body vibration and sound levels were
      recorded and heart parameters were obtained by ECG signal. RESULTS: Sound and
      whole-body vibration levels exceeded the recommended limits. Mean whole-body
      vibration and sound levels were 0.19 m/s(2) and 73 dBA, respectively. Higher
      whole-body vibration was associated with a lower heart rate (p < 0.05), and
      higher sound level was linked to a higher heart rate (p = 0.05). The heart rate
      variability was significantly higher at the end of the transport than at the
      beginning (p < 0.01). Poorer physiological status was associated with lower heart
      rate variability (p < 0.001) and a lower heart rate (p < 0.01). Infants wearing
      earmuffs had a lower heart rate (p < 0.05). CONCLUSIONS: Sound and whole-body
      vibration during neonatal transport exceed recommended levels for adults, and
      sound seem to have a more stressful effect on the infant than vibrations. Infants
      should wear earmuffs during neonatal transport because of the stress-reducing
      effect.

PMID- 21950548
TI  - Pharmacokinetics study about topical clobetasol on oral mucosa.
AB  - BACKGROUND: Clobetasol is the most potent topical corticosteroid used in oral
      medicine for muco-cutaneous diseases. Several papers reported about patients with
      cushingoid appearance, suggesting an adrenal suppression related to clobetasol
      systemic absorption after local application. Owing to the lack of studies, our
      goal is to assess whether transmucosal assimilation, after its application on
      oral mucosa, really occurs and to define clobetasol pharmacokinetics profile.
      METHODS: Data were recorded by collecting blood samples both on 10 patients in
      clobetasol therapy and on 14 healthy volunteers instructed about standardized
      clobetasol applications. A new technique of analytical chemistry was employed to
      detect its serum concentrations. RESULTS: Clobetasol absorption was ascertained,
      showing a certain accumulation rate. Different levels have been found in relation
      to oral disease and individual features (as smoking habits and presence of oral
      mucosa erosion). CONCLUSIONS: Our study validates clobetasol systemic
      transmucosal absorption, also recommending a careful monitoring of patients in
      corticosteroid therapy to avoid local and systemic adverse effects.

PMID- 21950549
TI  - Total synthesis of (+)-yohimbine via an enantioselective organocatalytic Pictet
      Spengler reaction.
AB  - The binolphosphoric acid-catalyzed Pictet-Spengler reaction of an N-(5-oxy-2,4
      pentadienyl)tryptamine derivative with methyl 5-oxo-2-(phenylseleno)pentanoate
      leads to the tetrahydro-beta-carboline in a 92:8 enantiomeric ratio. This product
      is easily converted into the substrate for a stereoselective intramolecular Diels
      Alder reaction of the type earlier reported by Jacobsen. These two key steps
      constitute the basis for a nine-step total synthesis of (+)-yohimbine from
      tryptamine. A similar asymmetric Pictet-Spengler reaction was applied to the
      synthesis of an intermediate in the recent total synthesis of corynantheidine by
      Sato.

PMID- 21950550
TI  - Differential effect of etanercept on cutaneous and joint lesions in psoriatic
      arthritis.

PMID- 21950551
TI  - Surrogate markers of transport distance for out-of-hospital cardiac arrest
      patients.
AB  - BACKGROUND: Transport of out-of-hospital cardiac arrest (OHCA) patients
      expeditiously to appropriately equipped hospitals is of paramount importance.
      OBJECTIVE: We sought to test the correlation of the centroids of geographic units
      with the actual transport distance for OHCA patients in order to determine the
      most appropriate surrogate marker of location for future planning, protocol
      development, and research projects. METHODS: This was a prospective,
      observational analysis of OHCA events in Portland, Oregon. Using geographic
      information systems (GISs), the locations of OHCA events and receiving hospitals
      were identified and geocoded for visual inspection and analysis. Transport
      distance was calculated via network transport distance and Euclidean distance
      from multiple surrogate markers of location (centroids of ZIP code, census tract,
      census block group, and census block). Actual distance from the location of the
      event was then compared with these surrogate markers to determine the accuracy of
      alternative markers of OHCA location. RESULTS: Two hundred seventy patients had
      location data recorded, 163 of whom were transported to a hospital for further
      care. The median transport distance was 5.17 miles. The transport distance of
      OHCA patients from the centroid of the census block had the best correlation
      (R(2) = 0.99) with actual transport distance, whereas the use of the centroid of
      ZIP codes as a surrogate location had the lowest correlation (R(2) = 0.21).
      CONCLUSIONS: The use of centroids of census blocks via network distance is a
      valid surrogate for actual location of an OHCA event when calculating transport
      distance.

PMID- 21950552
TI  - Reduced expression of myocardin and serum response factor in the cavernous tissue
      of diabetic rats.
AB  - This study aimed to investigate the expression of myocardin and serum response
      factor (SRF) in the cavernous tissue of diabetic rats. The experimental diabetes
      model was induced in 8-week-old male Sprague-Dawley rats (200-220 g) by a single
      administration of streptozotocin. Both the diabetes mellitus group (DM group, n =
      20) and the control group (NDM group, n = 10) were injected with a low dose of
      apomorphine to allow for the measurement and comparison of the corresponding
      penile erections. Western blot and qRT-PCR were used to determine the protein and
      mRNA expression levels of myocardin and SRF. Erectile function was significantly
      decreased in the DM group compared with the control group (P < 0.001). The mRNA
      and protein expression levels of myocardin and SRF were reduced in the cavernous
      tissue of diabetic rats compared with the control group (P < 0.001). It is
      concluded that diabetes inhibits the mRNA and protein expression of both
      myocardin and SRF in the cavernous tissue. This could play a key role in the
      development of erectile dysfunction in diabetic rats.

PMID- 21950553
TI  - Effects of copper nanoparticles exposure in the mussel Mytilus galloprovincialis.
AB  - CuO NPs are widely used in various industrial and commercial applications.
      However, little is known about their potential toxicity or fate in the
      environment. In this study the effects of copper nanoparticles were investigated
      in the gills of mussels Mytilus galloprovincialis, comparative to Cu(2+). Mussels
      were exposed to 10 MUg Cu.L(-1) of CuO NPs and Cu(2+) for 15 days, and biomarkers
      of oxidative stress, metal exposure and neurotoxicity evaluated. Results show
      that mussels accumulated copper in gills and responded differently to CuO NPs and
      Cu(2+), suggesting distinct modes of action. CuO NPs induced oxidative stress in
      mussels by overwhelming gills antioxidant defense system, while for Cu(2+)
      enzymatic activities remained unchanged or increased. CuO NPs and Cu(2+)
      originated lipid peroxidation in mussels despite different antioxidant
      efficiency. Moreover, an induction of MT was detected throughout the exposure in
      mussels exposed to nano and ionic Cu, more evident in CuO NPs exposure.
      Neurotoxic effects reflected as AChE inhibition were only detected at the end of
      the exposure period for both forms of copper. In overall, these findings show
      that filter-feeding organisms are significant targets for nanoparticle exposure
      and need to be included when evaluating the overall toxicological impact of
      nanoparticles in the aquatic environment.

PMID- 21950554
TI  - Metabolic comparison of radiolabeled bleomycin and bleomycin-glucuronide labeled
      with 99mTc.
AB  - The metabolic comparison of bleomycin (BLM) and bleomycin-glucuronide (BLMG)
      radiolabeled with (99m)Tc ((99m)Tc-BLM and (99m)Tc-BLMG, respectively) has been
      investigated in this study. Quality control procedures were carried out using
      thin-layer radiochromatography and high-performance liquid chromatography. To
      compare the metabolic behavior of BLM and its glucuronide conjugate radiolabeled
      with (99m)Tc, scintigraphic, and biodistributional techniques were applied using
      male New Zealand rabbits and Albino Wistar rats. The results obtained have shown
      that these compounds were successfully radiolabeled with a labeling yield of
      about 100%. Maximum uptakes of (99m)Tc-BLM and (99m)Tc-BLMG metabolized as N
      glucuronide were observed within 2 hours in the liver, the bladder, and the
      spinal cord for (99m)Tc-BLM and the lung, the liver, the kidney, the large
      intestine, and the spinal cord for (99m)Tc-BLMG, respectively. Scintigraphy and
      biodistributional studies performed on the experimental animals have shown that
      radiopharmaceutical potentials of these compounds are completely different. At
      the same time, uptake of the (99m)Tc-BLMG was found to be better than that of
      (99m)Tc-BLM.

PMID- 21950555
TI  - Inhibition of heme oxygenase-1 enhances the radiosensitivity in human nonsmall
      cell lung cancer a549 cells.
AB  - Abstract undergoing radiotherapy or chemotherapy failed to respond. The aim of
      this study was to evaluate whether Inhibitor of HO-1, zinc protoporphyrin IX
      (Znpp), enhances the radiosensitivity in human nonsmall cell lung cancer (NSCLC)
      A549 Cells. A549 cells were induced by Znpp and irradiated by X-rays. Then,
      expression of HO-1 was measured by real-time polymerase chain reaction. Cell
      survival was evaluated using the MTS assay and the clonogenic survival assay;
      apoptosis and cell cycle distribution were monitored by flow cytometry. First,
      overexpression of the HO-1 mRNA was found in treatment with irradiation alone in
      A549 cells, and expression of the HO-1 mRNA was reduced after combined treatments
      with 12 MUmol/L of Znpp and irradiation. Second, diminished cell viability
      percentage, decreased cell clonogenic survival fraction, enhanced cell apoptotic
      index, and increased percentage of cells in the G1 phase were found after
      combined treatments with 12 MUmol/L of Znpp and irradiation compared to either
      treatment alone (p<0.05). Inhibitor of HO-1, Znpp, can increase the
      radiosensitivity of human NSCLC A549 cells.

PMID- 21950556
TI  - Hypoxia-inducible factor-1alpha downregulation by small interfering RNA inhibits
      proliferation, induces apoptosis, and enhances radiosensitivity in chemical
      hypoxic human hepatoma SMMC-7721 cells.
AB  - Radiation plays an important role in the treatment of hepatoma. In order to
      improve its therapeutic ratio, there has been much interest in augmenting the
      effect of radiation on tumors by combining it with molecularly targeted
      therapeutics. Hypoxia-inducible factor-1 (HIF-1) is an excellent potential
      candidate for targeted molecular therapy to improve radiation outcome. In this
      study, HIF-1alpha-targeted small interfering RNA (siRNA) expression vector was
      constructed and transfected into human hepatoma SMMC-7721 cells, which followed
      by culture in CoCl(2)-induced hypoxia. HIF-1alpha downregulation by siRNA
      inhibited proliferation, induced apoptosis, and enhanced radiosensitivity in
      chemical hypoxic SMMC-7721 cells in vitro. These findings suggest that specific
      inhibition of HIF-1alpha expression in combination with radiotherapy would be
      expected to exert a strong antitumor effect on human hepatoma.

PMID- 21950557
TI  - Intra-arterial treatment with 90yttrium microspheres in treatment-refractory and
      unresectable liver metastases of neuroendocrine tumors and the use of 111in
      octreotide scintigraphy in the evaluation of treatment response.
AB  - PURPOSE: The aim of this study was to examine the efficacy of intra-arterial
      (90)Yttrium treatment in the management of unresectable hepatic neuroendocrine
      tumors (NET) metastases unresponsive to treatment and the role of (111)In
      octreotide scintigraphy in the evaluation of treatment response. METHODS:
      Thirteen (13) patients with a mean age of 53.3 years not eligible for surgical
      treatment were included. Before the procedure, routine tests for renal/hepatic
      functions and bilirubin levels as well as (99m)Tc-macroaggregated albumin test to
      detect any leakage to the lungs were done. Treatment doses were calculated using
      body surface area method and all patients received (90)Y resin microspheres
      through hepatic artery catheter. Abdominopelvic computed tomography (CT) and
      (111)In-octreotide scintigraphy were done before and after treatment. Patients
      were divided into two groups based on their treatment response as assessed by
      either (111)In-octreotide scintigraphy or CT: group 1, responders; group 2,
      nonresponders. RESULTS: For all patients, 1-year survival rate and overall
      survival was 84.7% and 20 months, respectively. Based on (111)In-octreotide
      scintigraphy findings, 1-year survival rate was 90% and 66.7% for responders and
      nonresponders, respectively, whereas corresponding overall survival was 21.3
      months and 15.3 months. Survival data based on CT findings were as follows: 1
      year survival rate, responders, 80%; nonresponders, 100%; overall survival,
      responders, 20.4 months, nonresponders, 18.5 months. CONCLUSIONS: Intra-arterial
      treatment with (90)Y has survival benefits in treatment-refractory liver
      metastases from NETs and it could be used in these patients. Since it is a
      functional imaging method, (111)In-octreotide scintigraphy may be better
      discriminates patients responding to treatment from patients not responding.

PMID- 21950558
TI  - 99mTc-d-penicillamine-glucuronide: synthesis, radiolabeling, in vitro and in vivo
      evaluation.
AB  - The current study was aimed at synthesizing a glucuronide derivative of D
      penicillamine (D-PA) to be used for imaging purposes. First of all, D-PA
      glucuronide (D-PA-Glu) was synthesized by experimental treatments starting with
      uridine 5'-diphospho-glucuronosyltransferase enzyme rich microsome preparate.
      Then, the synthesized compound was labeled with technetium ((99m)Tc) by using a
      reduction method with stannous chloride. Quality controls were performed by using
      high-performance liquid chromatography and thin-layer radio chromatography
      (TLRC). Radiolabeling yield of (99m)Tc-D-PA-Glu was more than 98% according to
      TLRC results. In vitro evaluations of radiolabeled complexes were investigated on
      PC-3 human prostate cancer cells. (99m)Tc-D-PA-Glu exhibited more accumulation on
      PC-3 cells versus (99m)Tc-D-PA at 240 minutes. In order to determine its
      radiopharmaceutical potential, biodistribution studies were carried out in male
      Albino Wistar rats. The biodistribution results of (99m)Tc-D-PA-Glu, showed the
      highest uptake in prostate at 120 minutes postinjection with the main excretion
      route being through kidneys and bladder. (99m)Tc-D-PA-Glu and (99m)Tc-D-PA have
      exhibited different biodistribution results.

PMID- 21950559
TI  - Withania somnifera root extracts induce skin darkening in wall lizard
      melanophores via stimulation of cholinergic receptors.
AB  - The effects of the root extract of Withania somnifera and its active ingredient
      Withaferin A on the isolated melanophores of the wall lizard H. flaviviridis were
      studied in order to establish the mechanism of skin darkening at the cellular
      level. Significant skin darkening activity of the extract of W. somnifera and
      Withaferin A was observed on the isolated melanophores of the wall lizard. The
      melanin dispersal effects leading to the darkening of the skin were antagonised
      by atropine and hyoscine, and were also found to be highly potentiated by
      neostigmine. These findings suggest that the extract of W. somnifera, as well as
      its active principle, mimic the action of acetylcholine in melanin dispersion,
      thus leading to skin darkening via stimulation of cholinergic receptors of
      muscarinic nature within the melanophores of the wall lizard.

PMID- 21950561
TI  - Organic macromolecular high dielectric constant materials: synthesis,
      characterization, and applications.
AB  - Hyperbranched and dendritic architectures have been targeted for various
      applications such as sensing, drug delivery, optical limiting, and light
      harvesting. One interesting development in this area has focused on utilizing the
      existence of long-range delocalization in hyperbranched structures to achieve
      high dielectric constants. In this Feature Article, we will review the creation
      and development of this concept, and we highlight our recent research progress in
      this aspect. In particular, we discuss (1) synthetic methods for a particular
      group of hyperbranched polymers; (2) detailed optical and electronic
      characterization of this group of hyperbranched polymers, revealing the design
      criteria for achieving a good combination of high dielectric constant and minimum
      loss in such materials; and (3) the importance and potential applications of
      these materials.

PMID- 21950560
TI  - Role of 5-HT(1)  receptor subtypes in the modulation of pain and synaptic
      transmission in rat spinal superficial dorsal horn.
AB  - BACKGROUND AND PURPOSE: 5-HT receptor agonists have variable nociceptive effects
      within the spinal cord. While there is some evidence for 5-HT(1A) spinally
      mediated analgesia, the role of other 5-HT(1) receptor subtypes remains unclear.
      In the present study, we examined the spinal actions of a range of 5-HT(1)
      agonists, including sumatriptan, on acute pain, plus their effect on afferent
      evoked synaptic transmission onto superficial dorsal horn neurons. EXPERIMENTAL
      APPROACH: For in vivo experiments, 5-HT agonists were injected via chronically
      implanted spinal catheters to examine their effects in acute mechanical and
      thermal pain assays using a paw pressure analgesymeter and a Hargreave's device.
      For in vitro experiments, whole-cell patch-clamp recordings of primary afferent
      evoked glutamatergic EPSC were made from lamina II neurons in rat lumbar spinal
      slices. KEY RESULTS: Intrathecal (i.t.) delivery of the 5-HT(1A) agonist R +/- 8
      OH-DPAT (30-300 nmol) produced a dose-dependent thermal, but not mechanical,
      analgesia. Sumatriptan and the 5-HT(1B), 5-HT(1D), 5-HT(1F) agonists CP93129,
      PNU109291 and LY344864 (100 nmol) had no effect on either acute pain assay. R +/-
      8-OH-DPAT (1 uM) and sumatriptan (3 uM) both reduced the amplitude of the evoked
      EPSC. In contrast, CP93129, PNU109291 and LY344864 (0.3-3 uM) had no effect on
      the evoked EPSC. The actions of both R +/- 8-OH-DPAT and sumatriptan were
      abolished by the 5-HT(1A) antagonist WAY100635 (3 uM). CONCLUSIONS AND
      IMPLICATIONS: These findings indicate that the 5-HT(1A) receptor subtype
      predominantly mediates the acute antinociceptive and cellular actions of 5-HT(1)
      ligands within the rat superficial dorsal horn.

PMID- 21950562
TI  - The development of two different malignancies in a patient with large congenital
      melanocytic nevus.
AB  - Patients with large congenital melanocytic nevus (LCMN) have a high risk of
      developing malignant melanoma (MM) and other malignancies. We report a case of a
      mesenchymal malignancy that best fit the diagnosis of a malignant peripheral
      nerve sheath tumor and subsequent development of a MM developing from a LCMN.
      There are no previous reports of a second primary malignant neoplasm arising from
      a LCMN.

PMID- 21950563
TI  - How children handle life when their mother or father is seriously ill and dying.
AB  - AIMS AND OBJECTIVES: The aim of this study was to describe and understand how
      children handle their life when a mother or father is dying. METHODOLOGICAL
      DESIGN AND JUSTIFICATION: The research design was phenomenological hermeneutic.
      The phenomenological approach enabled us to capture the concrete everyday life of
      the children as it is understood and experienced by the children themselves. The
      hermeneutical approach offered the possibility of reaching an understanding of
      the children's experiences. RESEARCH METHODS: Seven children aged 11-17 years
      participated in the study. Data were collected using qualitative interviews and
      video diaries. ETHICAL CONSIDERATIONS: The researcher complied with ethical
      guidelines that apply to all researchers and followed ethical guidelines for
      nursing research in the Nordic Countries (Northern Nurses Federation). The
      children's names were changed, and the data were treated confidentially.
      FINDINGS: Analysis produced an overarching theme of death's waiting room, with
      following sub-themes: Relating to death, when death becomes even more clearly
      manifest and handling life in death's waiting room. STUDY LIMITATIONS: This study
      focuses on a limited explored area; children's lived life with a dying parent.
      The study limits itself to focusing on children's life world; by choosing this
      focus, we have not included the relational aspects that are essential aspects of
      children's lives. One might focus on these aspects in a second study to shed
      further light on the children's lives. CONCLUSION: When children live in a family
      with a dying mother or father, they find that their home is transformed from a
      safe base into death's waiting room. The children use a variety of ways to handle
      the confrontation with death. Avoiding talking to the children will not protect
      them from their thoughts about death.

PMID- 21950564
TI  - The androgen receptor CAG repeat polymorphism as a risk factor of low serum
      testosterone and its cardiometabolic effects in men.
AB  - Previous studies reported correlations of CAG repeat length with sex hormone
      serum concentrations and cardiometabolic risk factors, but were limited by small
      cross-sectional samples. We used data of 1859 men aged 20-79 years from the
      population-based Study of Health in Pomerania (SHIP) to investigate the direct
      and modulating effects of CAG repeat length on androgen action and
      cardiometabolic risk factors. We performed cross-sectional and longitudinal
      linear and Poisson regression models adjusted for age, smoking, physical
      activity, alcohol consumption and body mass index. The CAG repeat length was
      categorized into quartiles and low total testosterone (TT) defined according to
      the age-specific (by decades) 10th percentile, respectively. Age-adjusted cross
      sectional linear regression models showed a positive association between CAG
      repeat length and serum testosterone concentrations [beta coefficient for TT,
      0.099 (p = 0.028) and for free T, 0.002 (p = 0.001), respectively]. After a 5.0
      year median follow-up period, men with CAG repeat length in the lowest quartile
      had an increased risk of incident low TT concentrations [relative risk (RR),
      2.31; 95% confidence interval (CI), 1.18-4.55]. We found no direct association
      between CAG repeat length and cardiometabolic risk factors in cross-sectional and
      longitudinal multivariable linear regression analyses; whereas men with longer
      CAG repeat length and low TT concentrations showed the highest risk of incident
      MetS (RR, 1.51; 95% CI, 1.05-2.16). CAG repeat length is a risk factor of
      incident low TT concentrations and a contributing factor of testosterone-related
      cardiometabolic effects. The added clinical value of a combined assessment of CAG
      repeat length and serum TT concentrations merits further investigation.

PMID- 21950565
TI  - Personality, fear of childbirth and cesarean delivery on demand.
AB  - OBJECTIVES:  To investigate both the psychological traits and the demographic
      factors associated with cesarean section on maternal demand.  DESIGN:  Cross
      sectional questionnaire study.  SETTING:  Delivery ward, Edith Wolfson Medical
      Center, Holon, Israel.  SAMPLE:  Fifty-nine healthy primigravida with a singleton
      pregnancy were recruited during 2009, of whom 28 requested and were delivered by
      cesarean section without obstetrical indication, whereas 31 opted for spontaneous
      vaginal delivery.  METHODS:  All questionnaires were administered to the two
      groups at term. Various psychological (fear of childbirth questionnaire, Millon
      Clinical Multiaxial Inventory III, Anxiety Sensitivity Index, State-Trait Anxiety
      Index and social support scale) as well as demographic variables were measured
      before labor and compared. A priori power calculation yielded a power of 95%.
      MAIN OUTCOME MEASURES: Fear of childbirth, various personality disorders and
      psychiatric clinical syndromes (29 Millon Clinical Multiaxial Inventory III
      scales), Anxiety Sensitivity, State Anxiety Index, social support and demographic
      variables.  RESULTS:  Differences in age and method of conceiving (p<0.001) were
      found between the groups. The study group reported a higher level of fear of
      childbirth (p<0.001), but no differences were found in all other personality
      characteristics measured (29 Millon Clinical Multiaxial Inventory III scales,
      State-Trait Anxiety, Anxiety Sensitivity and social support scale). The origin of
      the difference regarding the fear of childbirth was located to two specific
      questions: 'Have you always been afraid of giving birth?' and 'Have you sometimes
      thought of the delivery as something unnatural?'  CONCLUSIONS:  The only
      psychological variable associated with the choice for cesarean section on
      maternal request was the fear of childbirth.

PMID- 21950566
TI  - Analytical electron microscopy of black carbon and microaggregated mineral matter
      in Amazonian dark Earth.
AB  - Black carbon (BC) is one of the most stable forms of soil organic matter. Its
      surface functional groups and structure have been well characterized by a range
      of analytical methods. However, little is known about the mechanisms of
      interactions between the BC particles and the surrounding mineral matter. In this
      paper a range of microscopy techniques, such as transmission electron microscopy
      and scanning transmission electron microscopy, were used to investigate the
      possible reactions of BC particles within microaggregates (<2 mm) found in
      Amazonian dark Earth. Attention is given to the interactions that occur at the
      interfacial regions between the organic and inorganic phases. Examination of
      Amazonian dark Earth showed that the carbon-rich phase detected within the BC
      particles has a significant calcium concentration and a high density of
      micropores was found at the BC-mineral interface. These observations provide
      evidence to support suggested mechanisms of interaction between these phases.

PMID- 21950567
TI  - TGF-beta1 content in atherosclerotic plaques, TGF-beta1 serum concentrations and
      incident coronary events.
AB  - BACKGROUND: We tested the hypothesis that high TGF-beta1 content in
      atherosclerotic plaques and high TGF-beta1 serum levels are associated with lower
      risk of coronary events in two independent prospective studies. MATERIALS AND
      METHODS: In the prospective Athero-Express biobank study, total TGF-beta1 plaque
      levels were measured in 632 atherosclerotic lesions from patients who underwent
      carotid endarterectomy. In a population-based case-cohort study within the
      Monitoring of trends and determinants in cardiovascular disease
      (MONICA)/Cooperative Health Research in the Region of Augsburg (KORA) Augsburg
      studies, baseline total TGF-beta1 serum levels were measured in 333 individuals
      with and 1728 without incident coronary events. RESULTS: Patients with TGF-beta1
      content in their plaques above the study median did not have a lower risk of
      coronary events than patients with lower TGF-beta1 levels [adjusted HR (95% CI)
      1.46 (0.83-2.53); P = 0.16; mean follow-up 2.6 +/- 0.7 years] in the Athero
      Express biobank study. Cox proportional hazard models adjusting for age, sex,
      body mass index, metabolic factors, lifestyle factors and survey did not reveal a
      significant association between TGF-beta1 serum levels and incident coronary
      events [HR (95% CI) for increasing TGF-beta1 tertiles 1.0, 1.22 (0.88-1.68), 1.13
      (0.82-1.57); P = 0.47; mean follow-up: 10.8 +/- 4.6 years] in the MONICA/KORA
      Augsburg studies. CONCLUSION: Our results indicate that high TGF-beta1 content in
      human atherosclerotic plaques and high serum levels of TGF-beta1 are not
      associated with reduced risk of coronary events.

PMID- 21950577
TI  - Synthesis and structure of hypervalent diacetoxybromobenzene and aziridination of
      olefins with imino-lambda3-bromane generated in situ under metal-free conditions.
AB  - Ligand exchange of p-CF(3)C(6)H(4)BrF(2) with acetoxy groups using AcOH and
      Ac(2)O affords (diacetoxybromo)benzene in a high yield, which undergoes
      aziridination of alkenes in the presence of TfNH(2) and sulfamate esters in one
      pot under mild conditions. The aziridination with TfNH(2) proceeds
      stereospecifically with retention of stereochemistry of olefins at room
      temperature using limiting amounts of olefins under transition-metal-free
      conditions. The one-pot aziridination procedure using sulfamate esters can be
      applied to the intramolecular versions.

PMID- 21950578
TI  - A comparative study of the effects of low-dose topiramate versus sodium valproate
      in migraine prophylaxis.
AB  - The present study was performed to evaluate the efficacy of low-dose topiramate
      and compare it with sodium valproate that is prevalently prescribed as a migraine
      prophylaxis. This was a randomized, double-blind, parallel-group clinical trial
      on 56 patients who completed the course of study. Topiramate and valproate were
      administered at 50 mg/day and 400 mg/day, respectively, during the follow-up
      period. Frequency, intensity, duration, associated symptoms with headaches,
      analgesics use, as well as drugs' side effects were studied. Participants
      completed MIDAS and HIT-6 questionnaires before and after treatment. Frequency,
      intensity, and duration of migraine headaches as well as MIDAS score and
      symptomatic medications decreased significantly between repeated follow-up visits
      in both groups. Responder rate for patients treated with topiramate and valproate
      were 71.6% and 64.3%, respectively, and the difference between the two groups was
      not statistically significant. The reduction of headache severity in the
      topiramate group was significantly more than that in the valproate group (p =
      .027). During the study, no statistically significant reduction in associated
      symptoms with migraine were observed in both the groups. Topiramate dose of 50
      mg/day with fewer side effects in comparison with its higher doses may be an
      appropriate substitution for first-line migraine prophylaxis such as valproate.

PMID- 21950579
TI  - The conformation of the poly(ethylene glycol) chain in mono-PEGylated lysozyme
      and mono-PEGylated human growth hormone.
AB  - Covalent conjugation of poly(ethylene glycol) or "PEGylation" has proven an
      effective strategy to improve pharmaceutical protein efficacy by hindering
      recognition by proteases, inhibitors, and antibodies and by retarding renal
      clearance. Because it determines the strength and range of intermolecular steric
      forces and the hydrodynamic properties of the conjugates, the configuration of
      protein-conjugated PEG chains is the key factor determining how PEGylation alters
      protein in vivo circulation time. Mono-PEGylated proteins are typically described
      as having a protective PEG shroud wrapped around the protein, but recent dynamic
      light scattering studies suggested that conjugates adopt a dumbbell
      configuration, with a relatively unperturbed PEG random coil adjacent to the
      globular protein. We used small-angle neutron scattering (SANS) to distinguish
      between the dumbbell model and the shroud model for chicken-egg lysozyme and
      human growth hormone covalently conjugated to a single 20 kDa PEG chain. The SANS
      contrast variation technique was used to isolate the PEG portion of the
      conjugate. Scattering intensity profiles were well described by the dumbbell
      model and inconsistent with the shroud model.

PMID- 21950580
TI  - Distribution of mast cells in vaginal, cervical and uterine tissue of non
      pregnant mares: investigations on correlations with ovarian steroids.
AB  - Mast cells constitute part of the cellular immune system of the genital tract.
      They play a potential role in cervical remodelling during parturition and are
      subject to the influence of ovarian steroids. In this study, the influence of
      oestradiol-17beta and progesterone on the distribution of mast cells in equine
      vaginal, cervical and uterine tissue was evaluated. Genital tracts were retrieved
      from healthy mares at a local slaughterhouse. The cervix was divided along the
      longitudinal axis into five equivalent regions from cranial to caudal (R1 to R5).
      Toluidine blue staining was used for the detection of mast cells. Hormone values
      were determined via radioimmunoassay. In cervical tissue, mast cells were present
      at higher frequency and higher density than in vaginal and uterine tissue.
      Statistically significant differences were obtained between cervical R1 (cranial)
      and uterus as well as cervical R2 and uterus (p < 0.05). In cervical tissue, an
      association between the presence of mast cells and peripheral oestrogen
      concentrations was observed, whereas such correlation could not be established
      for vaginal and uterine tissue. With increasing oestradiol-17beta concentrations,
      the density of mast cells in cervical tissue increased to a statistically
      significant degree in the cranial (r = 0.46; p = 0.05) and caudal (r = 0.5; p =
      0.03) regions. We propose that mast cells play a role in the cyclic remodelling
      of the equine cervix during the course of the oestrous cycle. Elucidation of
      mechanisms controlling cervical remodelling could contribute to development of
      therapies for mares showing a lack in cervical opening during oestrus.

PMID- 21950581
TI  - Immunoregulatory potential of exopolysaccharide from Lactobacillus rhamnosus
      KL37: effects on the production of inflammatory mediators by mouse macrophages.
AB  - The ability to produce exopolysaccharides (EPS) is widespread among lactobacilli
      including Lactobacillus rhamnosus, the commonly used probiotic bacteria.
      Exopolysaccharides are a major component of the bacterial biofilm with a well
      documented impact on adherence of bacteria to host cells. However, their
      immunoregulatory properties are unknown. The aim of this study was to examine the
      immunostimulatory potential of EPS derived from L. rhamnosus KL37. We
      investigated the effect of EPS on the production of inflammatory mediators by
      mouse peritoneal macrophages and compared it with the effect of
      Lipopolysaccharide (LPS). Exopolysaccharides, at concentrations higher than those
      of LPS, stimulated production of both pro-inflammatory (TNF-alpha, IL-6, IL-12)
      and anti-inflammatory (IL-10) cytokines. Interestingly, analysis of the balance
      of TNF-alpha/IL-10 production showed a potential pro-inflammatory effect of EPS.
      Furthermore, our data demonstrate that exposure of macrophages to LPS induced a
      state of hyporesponsiveness, as indicated by reduced production of TNF-alpha
      after restimulation with either LPS or EPS ('cross-tolerance'). By contrast, EPS
      could make cells tolerant only to subsequent stimulation by the same stimulus. We
      also examined the relationship between TNF-alpha production and activation of
      mitogen-activated protein kinases (MAPKs) by EPS and LPS. Pretreatment of
      macrophages with specific inhibitors of p38 and ERK MAPKs reduced TNF-alpha
      production induced by both stimuli to the same extent. In conclusion, these data
      demonstrate that EPS can effectively stimulate production of inflammatory
      mediators by macrophages in vitro. However, to predict whether EPS could be
      clinically useful as an immunomodulatory agent, further in vivo studies with
      highly purified EPS are necessary.

PMID- 21950582
TI  - Storage time of blood products and transfusion-related acute lung injury.
AB  - BACKGROUND: Besides white blood cell antibodies in plasma-rich products, another
      cause of transfusion-related acute lung injury (TRALI) could be release of
      biologically active substances during storage of cellular blood products. We
      aimed to investigate the association of storage time and risk of TRALI for
      different product types. STUDY DESIGN AND METHODS: We compared storage time of
      blood products transfused within 6 hours before the onset of TRALI to storage
      time of a representative sample of all blood products transfused in the
      Netherlands. Generalized linear models were used to correct for confounding
      variables. RESULTS: Platelets (PLTs) in plasma transfused to TRALI patients were
      stored for 0.7 (95% confidence interval [CI], 0.073 to 1.3) days longer than
      those transfused to controls. The relative risk of TRALI, after receiving PLTs
      stored for 4 or 5 days, compared to 3 days or less, was 5.8 (95% CI, 0.99 to 110)
      and increased to 6.3 (95% CI, 1.1 to 118) after more than 5 days (i.e., 6 or 7
      days). CONCLUSIONS: While longer storage of buffy coat-derived PLTs was
      associated with an increased risk of TRALI, storage of plasma for up to 2 years
      and red blood cells for up to 35 days was not associated with the risk of TRALI.

PMID- 21950584
TI  - In situ evolution of trivalent chromium process passive film on Al in a corrosive
      aqueous environment.
AB  - In situ neutron reflectivity (NR) is used to observe the structure and evolution
      of a Trivalent Chromium Process (TCP) passive film on Al in a NaCl-D(2)O
      solution. Using a split liquid reflectivity cell we mimicked the corrosion
      process on the anodic sites in alloy AA 2024-T3 in a pitting scenario. The split
      cell separates the anodic and cathodic reactions, allowing NR observation of the
      corroding anodic surface under potential control. We observed the evolution of
      the TCP film on the Al anode and compared the degradation of the Al with and
      without TCP protection. When held at 100 mV above the open-circuit potential
      (OCP), unprotected aluminum dissolves at a rate of 120 A/h. By contrast, TCP
      coated Al is stable up to the pitting potential (200 mV above OCP). In the
      passive state D(2)O molecules penetrate the bulk TCP film by partially replacing
      the hydrate water. In spite of exchange of hydration water, the TCP film is
      stable and the underlying aluminum is fully protected. The passive character of
      the TCP film is due to a dense layer at the metal-TCP interface and/or to
      suppression of ion transport in the bulk film. As the pitting potential is
      approached the film swells and NaCl-D(2)O solution penetrates the TCP film. At
      this point, 50 vol % of the TCP film is occupied by bulk NaCl-D(2)O solution.
      Failure occurs by aluminum dissolution under the swollen TCP film as the imbibed
      solution contacts the Al metal. Further increase in potential leads to complete
      stripping of the TCP film.

PMID- 21950583
TI  - A modified regimen of pegylated liposomal doxorubicin, bortezomib and
      dexamethasone (DVD) is effective and well tolerated for previously untreated
      multiple myeloma patients.
AB  - The combination of pegylated liposomal doxorubicin (PLD), bortezomib and
      dexamethasone has shown efficacy in the treatment of multiple myeloma (MM)
      patients. Our earlier retrospective study suggested that modification of the
      doses, schedules and route of administration of these drugs appears to reduce
      toxicity without compromising anti-MM activity. As a result, we evaluated this
      modified drug combination in the frontline setting in a prospective multicentre
      phase II trial. Thirty-five previously untreated MM patients were enrolled.
      Dexamethasone IV 40 mg, bortezomib 1 mg/m(2)  and PLD 5 mg/m(2)  were
      administered on days 1, 4, 8 and 11 of a 4-week cycle. Patients were treated to
      their maximum response plus two additional cycles. The treatment regimen was
      discontinued after a maximum of eight cycles. Our modified schedule and dosing
      regimen achieved a high overall response rate of 86%, while showing a marked
      decrease in the incidence and severity of peripheral neuropathy, palmar-plantar
      erythrodysesthesia and myelosuppression compared to the standard dosing on a 3
      week cycle using these drugs. This modified regimen of dexamethasone, bortezomib
      and PLD shows improved tolerability and safety while maintaining a high response
      rate when compared to standard treatment with these agents in the frontline
      setting.

PMID- 21950586
TI  - Assessment of serum vascular endothelial growth factor and nail fold
      capillaroscopy changes in systemic lupus erythematosus with and without cutaneous
      manifestations.
AB  - Angiogenesis and microvascular endothelial injury play a role in the pathogenesis
      of systemic lupus erythematosus (SLE). Vascular endothelial growth factor (VEGF),
      a key regulator of angiogenesis, and nail fold capillaroscopy (NFC) have been
      investigated in few studies in SLE with no reports targeting SLE with cutaneous
      manifestations. To evaluate NFC changes and VEGF serum level in relation to
      disease activity in SLE patients with versus without cutaneous manifestations.
      Thirty SLE patients (15 with cutaneous manifestations [group I], 15 without
      [group II]) and 15 healthy controls were evaluated for VEGF serum levels, NFC
      changes and were related to disease activity. VEGF serum levels were
      significantly higher in patients than controls (median and interquartile range
      [IQR]: 2110.77, 471.09-4714.30 vs. 60.00, 14-366, respectively, P < 0.0001). VEGF
      cut-off value to predict SLE patients was more than 293 and to detect moderate
      and severe SLE activity was more than 422 pg/mL and more than 3800 pg/mL,
      respectively. Serum VEGF levels increased with increased disease activity (P <
      0.05). It was significantly higher in group I than group II (median and IQR:
      2624.74, 1801.39-4141.70 vs. 862.50, 180-2426.95, respectively, P < 0.05). Mean
      serum VEGF was significantly higher with NFC score 3 than 1 (P = 0.008). NFC
      score and SLE activity were significantly associated in patients (P < 0.05).
      Serum VEGF is significantly elevated in SLE patients with cutaneous
      manifestations and its cut-off values to detect different activity grades of SLE
      are identified. Abnormalities in NFC reflect the extent of microvascular
      involvement in SLE.

PMID- 21950587
TI  - Evaluation of the clinical efficacy of a betaine-containing mouthwash and an
      intraoral device for the treatment of dry mouth.
AB  - OBJECTIVE: An evaluation is made of the efficacy and safety of an intraoral
      device with a betaine (BET)-containing mouthwash in treating xerostomia. METHODS:
      A total of 105 patients with dry mouth (xerostomia) were included in a
      randomized, non-blinded, parallel-group, controlled clinical trial. The patients
      were assigned to one of the three groups: A (night guard), B (mouthwash), or C
      (night guard and mouthwash). A xerostomia questionnaire was administered, and
      unstimulated salivary flow was measured. The Oral Health Impact Profile (OHIP) -
      14 was assessed. All measurements were taken before and after treatment, which
      had a duration of 4 weeks. The patients in turn completed a treatment
      satisfaction questionnaire. RESULTS: Ninety patients (eight men and 82 women)
      completed the study. All three treatments alleviated the symptoms of xerostomia,
      with improvement in the OHIP-14 scores and sialometry findings. There were no
      adverse effects. Patient satisfaction with the treatment received showed no
      statistically significant differences among the three groups; though, the
      patients in group A considered treatment to have been extremely beneficial in 10%
      of the cases, while 43% considered it to have been beneficial. CONCLUSIONS: The
      daily use of a night guard and BET-containing mouthwash was seen to improve dry
      mouth during the 4-week duration of the study.

PMID- 21950589
TI  - A 35-year-old pregnant woman presenting with sudden cardiac arrest secondary to
      peripartum cardiomyopathy.
AB  - We present a case of successful resuscitation from cardiac arrest after 25
      minutes of ventricular fibrillation (VF) secondary to peripartum cardiomyopathy.
      This case highlights a rare disease, but also, more importantly, the successful
      use of the five links of survival: early access to 9-1-1, early cardiopulmonary
      resuscitation (CPR), early defibrillation, early advanced life support, and
      postresuscitative care. We also demonstrate the importance of high-quality
      resuscitation practices in order to achieve a successful outcome. Manual
      compressions can be performed at a guidelines-compliant rate. With training,
      users are able to achieve high compression fractions. Pre/post shock delays can
      be minimized to further increase compression fraction. Nationally, CPR
      interruptions are often long. We recommend closer attention to uninterrupted 2
      minute cycles of CPR, minimizing delays in CPR through training, and a focus on a
      closely choreographed approach. User review of transthoracic impedance feedback
      data should play a vital role in a cardiac arrest quality-improvement program.

PMID- 21950590
TI  - Functional characterisation of a natural androgen receptor missense mutation
      (N771H) causing human androgen insensitivity syndrome.
AB  - Androgen insensitivity syndrome (AIS) is an X-linked disorder due to mutations of
      androgen receptor (AR) gene. Various AR mutations have been identified, and the
      characterisation of these mutations greatly facilitates our understanding of AR
      structure-function. In this study, we have analysed an AR missense mutation
      (N771H) identified in patients with AIS. Functional analysis of the mutant AR was
      performed by in vitro mutagenesis-cotransfection assays. Compared to the wild
      type AR, the dose-response curve of dihydrotestosterone-induced transactivation
      activity in the mutant AR was greatly shifted to the right and significantly
      decreased. However, the maximal efficacy of transactivation activity in the
      mutant AR was similar to that of the wild type. Receptor binding assay indicated
      that the mutant AR had an approximately 2.5-fold lower binding affinity to
      dihydrotestosterone compared to the wild type. Western blot analysis showed that
      the size and the expression level of mutant AR in transfected cells were
      comparable to the wild type. These data underscore the importance of asparagine
      at amino acid position 771 of human AR in normal ligand binding and normal
      receptor function, and a mutation at this position results in androgen
      insensitivity in affected subjects.

PMID- 21950588
TI  - Alcohol increases the permeability of airway epithelial tight junctions in Beas
      2B and NHBE cells.
AB  - BACKGROUND: Tight junctions form a continuous belt-like structure between cells
      and act to regulate paracellular signaling. Protein kinase C (PKC) has been shown
      to regulate tight junction assembly and disassembly and is activated by alcohol.
      Previous research has shown that alcohol increases the permeability of tight
      junctions in lung alveolar cells. However, little is known about alcohol's effect
      on tight junctions in epithelium of the conducting airways. We hypothesized that
      long-term alcohol exposure reduces zonula occluden-1 (ZO-1) and claudin-1
      localization at the cell membrane and increases permeability through a PKC
      dependent mechanism. METHODS: To test this hypothesis, we exposed normal human
      bronchial epithelial (NHBE) cells, cells from a human bronchial epithelial
      transformed cell line (Beas-2B), and Beas-2B expressing a PKCalpha dominant
      negative (DN) to alcohol (20, 50, and 100 mM) for up to 48 hours.
      Immunofluorescence was used to assess changes in ZO-1, claudin-1, claudin-5, and
      claudin-7 localization. Electric cell-substrate impedance sensing was used to
      measure the permeability of tight junctions between monolayers of NHBE, Beas-2B,
      and DN cells. RESULTS: Alcohol increased tight junction permeability in a
      concentration-dependent manner and decreased ZO-1, claudin-1, claudin-5, and
      claudin-7 localization at the cell membrane. To determine a possible signaling
      mechanism, we measured the activity of PKC isoforms (alpha, delta, epsilon, and
      zeta). PKCalpha activity significantly increased in Beas-2B cells from 1 to 6
      hours of 100 mM alcohol exposure, while PKCzeta activity significantly decreased
      at 1 hour and increased at 3 hours. Inhibiting PKCalpha with Go-6976 prevented
      the alcohol-induced protein changes in both ZO-1 and claudin-1 at the cell
      membrane. PKCalpha DN Beas-2B cells were resistant to alcohol-induced protein
      alterations. CONCLUSIONS: These results suggest that alcohol disrupts ZO-1,
      claudin-1, claudin-5, and claudin-7 through the activation of PKCalpha, leading
      to an alcohol-induced "leakiness" in bronchial epithelial cells. Such alcohol
      induced airway-leak state likely contributes to the impaired airway host defenses
      associated with acute and chronic alcohol ingestion.

PMID- 21950591
TI  - Extramammary Paget's disease: evaluation of the histopathological patterns of
      Paget cell proliferation in the epidermis.
AB  - Extramammary Paget's disease (EMPD) is a rare malignant skin neoplasm. The
      prototypical pattern of tumor cell proliferation in the epidermis includes single
      cells and/or nest arrangements, mainly in the lower epidermis. Although other
      patterns have been recognized, they have not previously been investigated in
      detail. We aimed to examine the patterns of tumor cell proliferation in the
      epidermis. Surgical specimens were obtained from 38 patients with primary EMPD.
      We defined six patterns, in addition to the prototypical one: (i) glandular; (ii)
      acantholysis-like; (iii) upper nest; (iv) tall nest; (v) budding; and (vi) sheet
      like. There were 26 males and 12 females (mean age, 75.0 years). Lesions were
      located on the scrotum (26 cases) and vulva (12). There were 22 in situ EMPD and
      16 invasive EMPD. The frequencies of the different proliferation patterns were:
      glandular, 36.8%; acantholysis-like, 73.7%; upper nest, 68.4%; tall nest, 28.9%;
      budding, 47.4%; and sheet-like, 23.7%. Upper nest pattern and the presence of
      more than three patterns were significantly more frequent in invasive EMPD than
      in situ EMPD (P < 0.05). We identified the histopathological patterns of Paget
      cell proliferation in the epidermis in EMPD, and suggest that the characteristic
      patterns and the diversity of patterns could be associated with progression and
      dermal invasion in EMPD.

PMID- 21950593
TI  - In situ formation of N-trifluoroacetoxy succinimide (TFA-NHS): one-pot formation
      of succinimidyl esters, N-trifluoroacetyl amino acid succinimidyl esters, and N
      maleoyl amino acid succinimidyl esters.
AB  - A method for the in situ formation of N-trifluoroacetoxy succinimide (TFA-NHS)
      and its application in the formation of succinimidyl esters is presented. The
      developed method provides N-trifluoroacetyl and N-maleoyl amino acid succinimidyl
      esters from a variety of amino acids using a one-pot, high-yielding protocol.
      Investigations into the formation of an N-maleoyl amino acid succinimidyl ester
      supported the proposal of a revised reaction mechanism, and contributed to the
      optimization of the reaction conditions.

PMID- 21950594
TI  - Thermodynamics of cellulose solvation in water and the ionic liquid 1-butyl-3
      methylimidazolim chloride.
AB  - Cellulose is present in biomass as crystalline microfibrils held together by a
      complex network of intermolecular interactions making it difficult to initiate
      its hydrolysis and conversion to fuels. While cellulose is insoluble in water and
      most organic solvents, complete dissolution of cellulose can be achieved in
      certain classes of ionic liquids (ILs). The present study was undertaken to
      analyze the thermodynamic driving forces of this process and to understand how
      the anions and cations comprising an IL interact with the different moieties of
      glucose residues to cause dissolution. All-atom molecular dynamics (MD)
      simulations were performed at two extreme states of cellulose dissolution: a
      crystalline microfibril and a dissociated state in which all the glucan chains of
      the microfibril are fully separated from each other by at least four solvation
      shells. MD simulations of the two states were carried out in water and in the IL
      1-butyl-3-methylimidazolium chloride (BmimCl) to provide a comprehensive analysis
      of solvent effects on cellulose dissolution. The results reveal two important
      molecular aspects of the mechanism of cellulose dissolution. The first is that
      the perturbation of solvent structures by the dissolved glucan chains can be a
      crucial factor in determining solubility, particularly for the insolubility of
      cellulose in water at 300 K. Second, both the Cl(-) and the Bmim(+) ions of
      BmimCl interact with the moieties of glucan residues that form intersheet
      contacts, the most robust component of the interaction network of crystalline
      cellulose. Cl(-) anions can form hydrogen bonds (HBs) with the hydroxyl groups of
      glucan chains from either the equatorial or the axial directions. For Bmim(+)
      cations, the calculated density profiles reveal that the contacts with glucan
      chains along the axial directions are closer than those along the equatorial
      directions. On the basis of the results of atomistic MD simulations, we propose
      that interacting with glucan chains along axial directions and disrupting the
      intersheet contacts of cellulose is an important ability of cellulose
      pretreatment solvents.

PMID- 21950592
TI  - Low dose of propranolol down-modulates bone resorption by inhibiting inflammation
      and osteoclast differentiation.
AB  - BACKGROUND AND PURPOSE: Bones are widely innervated, suggesting an important role
      for the sympathetic regulation of bone metabolism, although there are
      controversial studies. We investigated the effects of propranolol in a model of
      experimental periodontal disease. EXPERIMENTAL APPROACH: Rats were assigned as
      follows: animals without ligature; ligated animals receiving vehicle and ligated
      animals receiving 0.1, 5 or 20 mg.kg(-1) propranolol. After 30 days, haemodynamic
      parameters were measured by cardiac catheterization. Gingival tissues were
      removed and assessed for IL-1beta, TNF-alpha and cross-linked carboxyterminal
      telopeptides of type I collagen (CTX) by elisa, or intercellular adhesion
      molecule 1 (ICAM-1), receptor activator of NF-kappa B ligand (RANKL) and
      osteoprotegerin (OPG) by Western blot analysis. Sections from the mandibles were
      evaluated for bone resorption. Also, we analysed the ability of propranolol to
      inhibit osteoclastogenesis in vitro. RESULTS: Propranolol at 0.1 and 5 mg.kg(-1)
      reduced the bone resorption as well as ICAM-1 and RANKL expression. However, only
      0.1 mg.kg(-1) reduced IL-1beta, TNF-alpha and CTX levels as well as increased the
      expression of OPG, but did not alter any of the haemodynamic parameters.
      Propranolol also suppressed in vitro osteoclast differentiation and resorptive
      activity by inhibiting the nuclear factor of activated T cells (NFATc)1 pathway
      and the expression of tartrate-resistant acid phosphatase (TRAP), cathepsin K and
      MMP-9. CONCLUSIONS AND IMPLICATIONS: Low doses of propranolol suppress bone
      resorption by inhibiting RANKL-mediated osteoclastogenesis as well as
      inflammatory markers without affecting haemodynamic parameters.

PMID- 21950595
TI  - Specimen labelling: before or after collection?

PMID- 21950597
TI  - Detection and quantification of M-proteinemia: comparison of various methods for
      serum protein electrophoresis.
AB  - BACKGROUND: Detection and quantification of monoclonal proteins is hampered when
      the monoclonal peak coincides with one of the regular bands in serum
      proteinelectrophoresis. The objective of this study was to evaluate four
      procedures for serum proteinelectrophoresis with respect to detection and
      quantification of monoclonal proteins. METHODS: For 466 patient samples with a
      monoclonal protein, three variants of agarose gel electrophoresis (5-band, split
      beta and high resolution) and one variant of capillary electrophoresis were
      compared with the results of the routinely used agarose gel electrophoresis
      followed by immunofixation analysis using specific or pentavalent antisera.
      RESULTS: In total, 310 patient samples were analyzed by the four methods,
      consisting of 295 samples with a monoclonal protein, seven with oligoclonal bands
      and eight without any bands. Suspicion of a monoclonal protein was raised in
      295/256/256/232/265 of the samples using the reference/5-band/split-beta/high
      resolution/capillary procedure. In 152/147/135/142/126 of the samples the
      concentration of monoclonal protein was >1.0 g/L and in 51/33/53/33/67 of the
      cases, the monoclonal protein was not separated from one of the normal protein
      zones. CONCLUSIONS: In high resolution agarose gel electrophoresis, monoclonal
      bands of low concentration often remain undetected. In split-beta agarose gel
      electrophoresis as well as capillary electrophoresis monoclonal bands more often
      were not separated from the regular protein bands.

PMID- 21950598
TI  - Comparison of two immunoassays for determining hepatitis B virus serum markers.
AB  - BACKGROUND: To evaluate and compare the detection efficacy of serum hepatitis B
      virus (HBV) markers by two immunoassays: electrochemiluminescence immunoassay
      (ECLIA) and enzyme-linked immunosorbent assay (ELISA). METHODS: ECLIA and ELISA
      were used to analyze 359 serum samples, including 64 HBsAg/anti-HBs coexistence
      serological pattern samples (samples positive for both HBsAg and anti-HBs), 24
      HBeAg/anti-HBe coexistence serological pattern samples (samples positive for both
      HBeAg and anti-HBe), and 271 normal serological pattern samples (negative for
      either of the combinations). RESULTS: In the normal serological pattern samples,
      the concordance rates of the two methods in detecting serum HBV markers were as
      follows: 97.05% for HBsAg, 92.62% for anti-HBs, 100% for HBeAg, 76.75% for anti
      HBe, and 58.67% for anti-HBc. The differences in the qualitative criteria for
      anti-HBc and anti-HBe were primarily responsible for the discrepancy between the
      two methods (kappa-values of 0.657 and 0.253, respectively). Most weak positive
      results, determined by ECLIA, were negative determined by ELISA, whereas the
      results of HBsAg, anti-HBs, and HBeAg detection were generally consistent. In the
      HBsAg/anti-HBs coexistence serological pattern samples, the concordance rates of
      HBsAg and anti-HBs detection were 98.44% and 34.38%, respectively. The positive
      rate of ELISA does not vary as the COI (cut-off index) varies which was
      determined by ECLIA; in the HBeAg/anti-HBe coexistence serological pattern
      samples, the concordance rates of HBeAg and anti-HBe detection were 45.83% and
      79.17%, respectively. Most weak positive results, determined by ECLIA, were
      negative when determined by ELISA. CONCLUSION: The discrepancies between the two
      assays in normal serological patterns samples and HBeAg/anti-HBe coexistence
      serological pattern samples were mostly due to the different sensitivity of the
      two assays, but for the HBsAg/anti-HBs coexistence serological pattern samples,
      the discrepancy was not caused by the different sensitivity. It is the difference
      in determining anti-HBs which led to the discrepancy.

PMID- 21950599
TI  - Photoreduction of chlorothalonil fungicide on plant leaf models.
AB  - Photodegradation is seldom considered at the surface of vegetation after crop
      spraying. Chlorothalonil, a broad-spectrum foliar fungicide with a very
      widespread use worldwide, was considered. To represent the waxy upper layer of
      leaves, tests were performed within thin paraffin wax films or in n-heptane.
      Laser flash photolysis together with steady-state irradiation in n-heptane
      allowed the determination of the photodegradation mechanisms Chlorothalonil
      ability to produce singlet oxygen was measured; noteworthy its efficiency is
      close to 100%. Additionally, chlorothalonil photodegradation mainly proceeds
      through reductive dechlorination. In these hydrophobic media, a radical mechanism
      was evidenced. Photochemical tests on wax films under simulated solar light show
      that formulated chlorothalonil is more reactive than pure chlorothalonil. The
      field-extrapolated half-life of photolysis on vegetation was estimated to 5.3
      days. This value was compared to the half-lives of penetration and volatilization
      available in the literature. It appears that chlorothalonil dissipation from
      crops is ruled by both photodegradation and penetration. The relative importance
      of the two paths probably depends on meteorological factors and on
      physicochemical characteristics of the crop leaf cuticle.

PMID- 21950596
TI  - Recent progress and clinical importance on pharmacogenetics in cancer therapy.
AB  - Recent advances have provided unprecedented opportunities to identify prognostic
      and predictive markers of efficacy of cancer therapy. Genetic markers can be used
      to exclude patients who will not benefit from therapy, exclude patients at high
      risk of severe toxicity and adjust dosing. Genomic approaches for marker
      discovery now include genome-wide association studies and tumor DNA sequencing.
      The challenge is now to select markers for which there is enough evidence to
      transition them to the clinic. The hurdles include the inherent low frequency of
      many of these markers, the lengthy validation process through trials, as well as
      legislative and economic hurdles. Attempts to answer questions about certain
      markers more quickly have led to an increased popularity of trials with
      enrichment design, especially in light of the dramatic phase I results seen in
      recent months. Personalized medicine in oncology is a step closer to reality.

PMID- 21950600
TI  - Depressive mood in women at childbirth predicts their mood and relationship with
      infant and partner during the first year postpartum.
AB  - BACKGROUND: Although many studies have reported negative impact of maternal
      depressive symptoms on family relations, few studies have explored whether or not
      early depressive symptoms influence interfamily relationships. The aim was to
      describe first-time mothers' feelings for their infant and partner during the
      first postpartum year in relation to maternal depressive symptoms. Research
      questions were addressed about: What is the prevalence of maternal depressive
      symptoms 10 days postpartum? How does maternal depressive symptoms on day 10
      relate to her mood and feelings for the infant and partner at days 3 and 10, and
      at 6 and 12 months postpartum? METHODS: A longitudinal study with first-time
      mothers, normal pregnancies, giving birth to healthy babies participated in the
      study; altogether, n = 419. Depressive symptoms were measured by Edinburgh
      Postnatal Depression Scale (EPDS) at 3 and 10 days. Additional questionnaires
      assessing the woman's mood and relationship with her infant and partner were
      filled out at days 3 and 10, and at 6 and 12 months postpartum. RESULTS: Twenty
      two per cent of the women scored high on EPDS on day 10 postpartum. In addition,
      low mood seemed to remain prevalent over the baby's first year, as confirmed by
      the mood scale at 6 and 12 months postpartum. Women with depressive symptoms
      showed less closeness, warmth and confidence as measured by the infant and
      partner relationship scales over the first year. Mothers with a high EPDS score
      on day 3 scored less optimal on the relationship scale to the infant at days 3
      and 10, but not 6 or 12 months postpartum. CONCLUSIONS: To screen women for
      depressive symptoms, 10 days postpartum seems to be predictive of maternal
      assessment of maternal-infant relationship throughout the first year and enables
      early intervention.

PMID- 21950601
TI  - Prospective risk of fetal death in uncomplicated monochorionic twins.
AB  - A retrospective cohort study was carried out in a university teaching hospital to
      determine the prospective risk of unexpected fetal death in uncomplicated
      monochorionic diamniotic (MCDA) twin pregnancies after viability. All MCDA twins
      delivered at or after 24 weeks' gestation from July 1999 to July 2007 were
      included. Pregnancies with twin-twin transfusion syndrome, growth restriction,
      structural abnormalities, or twin reversed arterial perfusion sequence were
      excluded. Of the 144 MCDA twin pregnancies included in our analysis, the risk of
      intrauterine death was 4.9%. The prospective risk of unexpected intrauterine
      death was 1 in 43 after 32 weeks' gestation and 1 in 37 after 34 weeks'
      gestation. Our results demonstrate that despite close surveillance, the
      unexpected intrauterine death rate in uncomplicated MCDA twin pregnancies is
      high. This rate seems to increase after 34 weeks' gestation, suggesting that a
      policy of elective preterm delivery warrants evaluation.

PMID- 21950602
TI  - Macrocycles that inhibit the binding between heat shock protein 90 and TPR
      containing proteins.
AB  - Heat shock protein 90 (Hsp90) accounts for 1-2% of the total proteins in normal
      cells and functions as a molecular chaperone that folds, assembles, and
      stabilizes client proteins. Hsp90 is overexpressed (3- to 6-fold increase) in
      stressed cells, including cancer cells, and regulates over 200 client and co
      chaperone proteins. Hsp90 client proteins are involved in a plethora of cellular
      signaling events including numerous growth and apoptotic pathways. Since pathway
      specific inhibitors can be problematic in drug-resistant cancers, shutting down
      multiple pathways at once is a promising approach when developing new
      therapeutics. Hsp90's ability to modulate many growth and signaling pathways
      simultaneously makes this protein an attractive target in the field of cancer
      therapeutics. Herein we present evidence that a small molecule modulates Hsp90
      via binding between the N and middle domain and allosterically inhibiting the
      binding interaction between Hsp90 and four C-terminal binding client proteins:
      IP6K2, FKBP38, FKBP52, and HOP. These last three clients contain a
      tetratricopeptide-repeat (TPR) region, which is known to interact with the MEEVD
      sequence on the C-terminus of Hsp90. Thus, this small molecule modulates the
      activity between co-chaperones that contain TPR motifs and Hsp90's MEEVD region.
      This mechanism of action is unique from that of all Hsp90 inhibitors currently in
      clinical trials where these molecules have no effect on proteins that bind to the
      C-terminus of Hsp90. Further, our small molecule induces a Caspase-3 dependent
      apoptotic event. Thus, we describe the mechanism of a novel scaffold that is a
      useful tool for studying cell-signaling events that result when blocking the
      MEEVD-TPR interaction between Hsp90 and co-chaperone proteins.

PMID- 21950613
TI  - Triazine-based vanilloid 1 receptor open channel blockers: design, synthesis,
      evaluation, and SAR analysis.
AB  - The thermosensory transient receptor potential vanilloid 1 channel (TRPV1) is a
      polymodal receptor activated by physical and chemical stimuli. TRPV1 activity is
      drastically potentiated by proinflammatory agents released upon tissue damage.
      Given the pivotal role of TRPV1 in human pain, there is pressing need for
      improved TRPV1 antagonists, the development of which will require identification
      of new pharmacophore scaffolds. Uncompetitive antagonists acting as open-channel
      blockers might serve as activity-dependent blockers that preferentially modulate
      the activity of overactive channels, thus displaying fewer side effects than
      their competitive counterparts. Herein we report the design, synthesis,
      biological evaluation, and SAR analysis of a family of triazine-based compounds
      acting as TRPV1 uncompetitive antagonists. We identified the triazine 8aA as a
      potent, pure antagonist that inhibits TRPV1 channel activity with nanomolar
      efficacy and strong voltage dependency. It represents a new class of activity
      dependent TRPV1 antagonists and may serve as the basis for lead optimization in
      the development of new analgesics.

PMID- 21950614
TI  - Antioxidant potential in callus culture of Artemisia amygdalina Decne.
AB  - This study was conducted to analyse the free radical scavenging potential of
      callus obtained from nodal segments and leaf explants of Artemisia amygdalina
      Decne. The explants were inoculated on MS medium augmented with various
      concentrations of BAP, Kn, NAA and 2,4-D for callus induction. In this study,
      12.42 g of callus developed from the leaf explant on MS (NAA 10 + BAP 7.5 uM) and
      8.81 g of callus developed from nodal explant on NAA 2 uM+BAP 2 uM. Callus raised
      from both explants on all treatments seemed non-regenerative but BAP 2 uM
      produced 7.33 shoots and BAP 15 uM produced callus and 5 shoots per nodal
      segment. Callus was analysed for antioxidant activity via DPPH, riboflavin
      photoxidation and DNA damage assays. Methanol and aqueous extracts show more
      scavenging in DPPH, deoxyribose assay and in contrast, petroleum ether and ethyl
      acetate extracts show higher activity in riboflavin photoxidation assay.
      Tocopherol, ascorbic acid and BHT were used as controls.

PMID- 21950615
TI  - Educational support for research utilization and capability beliefs regarding
      evidence-based practice skills: a national survey of senior nursing students.
AB  - AIM: The aim of the study was to investigate Swedish university nursing students'
      experience of educational support for research utilization and capability beliefs
      regarding evidence-based practice skills. BACKGROUND: Nursing programmes are
      offered at 26 universities in Sweden and even though there are common regulations
      for nursing education at the national level, substantial variations are found in
      local curricula. Little is known about students' capability beliefs regarding
      evidence-based practice skills, particularly in comparison across universities.
      METHODS: A cross-sectional survey design using self-administered postal
      questionnaires was conducted in 2006. A total of 1440 students (from 26 different
      universities) participated, constituting 68% of the national population of
      nursing students in their 6th and final semester. RESULTS: Campus education
      supported the students to a greater extent than clinical education in following
      the development of knowledge in an area of interest, using research findings, and
      acquiring knowledge on how to pursue changes in clinical practice. Perceived
      support during campus education varied between universities. Students reported
      high capability beliefs regarding evidence-based practice skills, but large
      differences were found between universities for: stating a searchable question,
      seeking out relevant knowledge and critically appraising and compiling best
      knowledge. CONCLUSION: The identified differences between universities concerning
      the students' perceived support for research utilization and their capability
      beliefs regarding evidence-based practice skills have implications for curricula,
      pedagogical perspectives in nursing education and the potential to implement
      evidence-based practice in healthcare settings. Further studies are warranted to
      investigate students' individual characteristics and organizational
      characteristics as determinants of research utilization support and capability
      beliefs regarding evidence-based practice skills.

PMID- 21950616
TI  - Spermatozoa DNA damage measured by sperm chromatin structure assay (SCSA) and
      birth characteristics in children conceived by IVF and ICSI.
AB  - High levels of spermatozoa DNA damage hinder fertility in vivo but not in vitro.
      It is a source of worry that following in vitro fertilization (IVF) spermatozoa
      DNA damage, if not repaired by the oocyte, might have a negative impact on the
      offspring. The aim of this study was to assess if a high spermatozoa DNA
      Fragmentation Index (DFI) is associated with alterations in birthweight (BW)
      and/or gestational length in IVF children. One hundred and thirty-one singleton
      pregnancies established by standard IVF or intracytoplasmic sperm injection
      (ICSI) were included in the study. DFI was measured by sperm chromatin structure
      assay (SCSA) in semen samples used for fertilization. DFI was categorized as low
      and high, using 20, 30, 40 and 50% as cut-off levels. Birthweight, gestational
      age, as well as gestational age adjusted BW score were used in a linear
      regression model as end points For none of the tested birth characteristics,
      statistically significant differences between the groups with low and high DFI
      were seen regardless of whether 20, 30, 40 or 50% were used as cut-off levels,
      both when the IVF and ICSI data were merged or analysed separately. Spermatozoa
      DNA damage as assessed by SCSA is not associated with BW or gestational length in
      IVF and ICSI children.

PMID- 21950617
TI  - Age assessment of young asylum seekers.
AB  - During 2009, 15,100 unaccompanied children sought asylum in Europe. Many of them
      came from 'failed states' like Somalia and Afghanistan where official documents
      with exact birth dates are rarely issued. This has led to requests to health care
      professionals in many countries to assist migration authorities in determining
      whether a young asylum seeker is a child or an adult. Many different methods are
      currently employed in Europe for this purpose by dentists, paediatricians,
      radiographers and social workers, but no currently available method has been
      demonstrated to have the accuracy needed to be of real use in this decision.
      Unclear guidelines and arbitrary practices may lead to alarming shortcomings in
      the protection of this high-risk group of children and adolescents in Europe.
      Medical participation, as well as non-participation, in these dubious decisions
      raises a number of ethical questions. CONCLUSION: To improve care for young
      asylum seekers with undetermined age, we suggest better legal procedures for the
      determination of age and a more flexible approach to chronological age.

PMID- 21950618
TI  - Failure to thrive in infants with complicated facial hemangiomas.
AB  - We have observed that some children with facial hemangiomas of infancy have
      feeding difficulties coincident with periods of failure to thrive. We evaluated
      the early oral sensory and feeding experiences of four children with facial
      hemangiomas through medical record review and parental surveys to investigate
      their contribution to the patients' failure to thrive. All children with feeding
      irregularities experienced some degree of oral sensory impairment and required
      early oral sensory intervention, but there were varying reports of difficulty or
      delay in the development of oral feeding. The nature of these difficulties is
      discussed. Infants with complicated facial hemangiomas with perioral and airway
      involvement may be at higher risk for feeding and oral sensory problems. We
      recommend close monitoring for failure to thrive and early evaluation by speech
      or occupational therapists.

PMID- 21950619
TI  - Estimation of left ventricular function using a novel acoustic-based device.
AB  - BACKGROUND: We examined the feasibility of estimating left ventricular ejection
      fraction (LVEF) by a novel acoustic-based device [vibration response imaging
      (VRI); Deep Breeze]. METHODS: One hundred and forty-one subjects (117 patients
      and 24 healthy volunteers; age 55 +/- 15 years, 82% men) were examined by both
      VRI and echocardiography. LVEF was determined by echocardiography (echo-LVEF)
      using the biplane Simpson's method. Low-frequency acoustic signals (10-70 Hz)
      were recorded by VRI from the left posterior thorax by a matrix of 36 microphones
      during 8 s of breath holding, and an electrocardiogram was recorded
      simultaneously. The acoustic signals were processed digitally, and an algorithm
      designed to estimate LVEF was developed (VRI-LVEF), based on a combination of
      multiple acoustic (systolic and diastolic acoustic signals, beat-to-beat
      variability of acoustic signals and propagation of acoustic signals throughout
      the matrix), electrocardiographic and clinical parameters. RESULTS: Mean echo
      LVEF was 51 +/- 15% (range, 11-76%). Echo-LVEF was reduced (< 50%) in 55 subjects
      (39%) and severely reduced (< 35%) in 28 subjects (20%). VRI-LVEF calculated by a
      multivariate algorithm correlated significantly with echo-LVEF (R(2) = 0.59; P <
      0.001). VRI-LVEF accurately predicted the presence of reduced (< 50%) or severely
      reduced (< 35%) echo-LVEF, with sensitivities of 84% and 82%, specificities of
      86% and 91%, positive predictive values of 79% and 70% and negative predictive
      values of 89% and 95%, respectively. CONCLUSIONS: LVEF can be estimated using a
      novel acoustic-based device. This device may assist in triage of patients
      according to LVEF prior to definitive assessment of LVEF by echocardiography.

PMID- 21950620
TI  - Thieno[3,2-b]pyrrolo donor fused with benzothiadiazolo, benzoselenadiazolo and
      quinoxalino acceptors: synthesis, characterization, and molecular properties.
AB  - Nitrogen-bridged donor-acceptor multifused dithienopyrrolobenzothiadiazole
      (DTPBT) and dibenzothiadiazolopyrrolothiophene (DBTPT) were successfully
      synthesized by intramolecular Cadogan annulation. The electron-deficient
      benzothiadiazole unit in DTPBT can be converted to benzoselenadiazole and
      quinoxaline moieties through reduction/cyclization to generate
      dithienopyrrolobenzoselenadiazole (DTPBSe) and dithienopyrroloquinoxaline
      (DTPQX), respectively. The nitrogen atoms function as the bridges for covalent
      planarization to induce intermolecular interaction and intramolecular charge
      transfer.

PMID- 21950621
TI  - Demographics of successful, unsuccessful and deferral visits at six blood centers
      over a 4-year period.
AB  - BACKGROUND: Descriptions of donor demographics are of value in formulating
      recruitment and retention strategies. The demographics of successful (SV),
      unsuccessful (UV; meaning a nonuseable unit), and deferred (DV) donor visits over
      a 4-year period were investigated using Retrovirus Epidemiology Donor Study
      (REDS)-II databases. STUDY DESIGN AND METHODS: Fourteen deferral categories were
      created that included low hematocrit (Hct) or hemoglobin (Hb), feeling unwell,
      malaria travel, malaria other, couldn't wait, blood pressure or pulse, medical
      diagnosis, medication, test results, higher-risk behavior, variant Creutzfeldt
      Jakob disease (CJD), CJD, needle exposure or tattoo, and other. Rates per 10,000
      donor presentations were determined for each category globally and for six
      subcategorizations (first-time or repeat donor status, sex, race/ethnicity, age,
      education, and fixed or mobile donation location). Deferral rates were also
      calculated on simultaneous stratifications of donor status, sex, and
      race/ethnicity. RESULTS: Of 5,607,922 donor presentations there were 4,553,145
      SVs (81.2%), 302,828 UVs (5.4%), and 751,381 DVs (13.4%). Overall rates of
      deferral ranged from 0.6 per 10,000 presentations for CJD, human growth hormone,
      or dura mater exposure to 777 per 10,000 presentations for low Hct or Hb.
      Deferral rates were remarkably different by first-time or repeat donor status,
      sex, race/ethnicity, and other demographics. The highest overall deferral rate
      was 3953 per 10,000 presentations, or nearly 40% in first-time, female, Asian
      donors, and the lowest rate was 5.6% in repeat, male, white donors. CONCLUSION:
      Successful donation visits according to demographic characteristics need to be
      placed within the context of all donor visits. Deferral rates indicate that the
      burden of donor deferral is high. Efforts to expand the diversity of the donor
      base through recruitment of minority donors may bring additional challenges
      because certain deferral reasons were proportionally much higher in these groups.

PMID- 21950622
TI  - Translocation of active mitochondria during buffalo (Bubalus bubalis) oocytes in
      vitro maturation, fertilization and preimplantation embryo development.
AB  - Mitochondria are energy-supplying organelles, whose distribution and functional
      integrity are necessary for cell survival and development. In this study, the
      mitochondrial distribution pattern and activity during buffalo oocyte in vitro
      maturation, fertilization and preimplantation embryo development were revealed
      using a fluorescent dye and confocal laser scanning microscopy. Distribution of
      active mitochondria changed during buffalo oocyte in vitro maturation. Active
      mitochondria were transferred from the outer to inner and perinuclear cytoplasm
      as oocytes matured in vitro and aggregated around the pronuclei in the fertilized
      eggs. Active mitochondria were also observed in preimplantation embryos. In the
      two-cell stage, they were distributed throughout the cytoplasm. From four-cell to
      the spherical embryonic stages, active mitochondria translocated to the
      perinuclear and the periphery of the cytoplasm. These results confirm that
      mitochondria play an important role in oocyte and embryo. The distribution of
      active mitochondria might be a marked feature of buffalo oocyte maturation,
      fertilization and preimplantation embryo development in vitro.

PMID- 21950623
TI  - A 35-month prospective study on onset of scabies in a psychiatric hospital:
      discussion on patient transfer and incubation period.
AB  - This study was conducted to evaluate the risk factors of scabies introduction
      into a hospital. We addressed the following question: Do patients transferred
      from other institutions pose a higher risk than patients from the community? From
      July 2003 to May 2006, a trained physician surveyed the inpatients and staff of a
      psychiatric hospital (six wards, 300 beds) on a monthly basis. During the study
      period, specific infection control measures beyond standard precautions, such as
      prophylactic treatment, were not adopted. There were 333 newly-admitted patients
      during the study period and among them, 122 were transferred from other
      institutions. Seven patients were diagnosed with scabies. Two of these patients
      were infected while in the hospital (secondary infection), thus the number of
      introduced scabies cases (index cases) was five. Four of the index cases were
      transferred from other institutions (three from psychiatric hospitals and one
      from a nursing home). The source of infection for one index case was unexplained.
      The rate of scabies infection among transferred patients was 3.3% while the
      infection rate among patients from the community was 0.5%. Therefore, transferred
      patients pose a higher risk than those from the community. The average time from
      admission to diagnosis of scabies was 141 days (range 34-313 days). The hospital
      personnel checked the skin condition of all patients at admission and none of the
      four patients showed symptoms of scabies.

PMID- 21950625
TI  - The influence of psoriatic plaques pretreatment with crude coal tar vs.
      petrolatum on the efficacy of narrow-band ultraviolet B: a half-vs.-half intra
      individual double-blinded comparative study.
AB  - BACKGROUND/PURPOSE: The value of psoriatic plaques pretreatment with specific
      topical preparations in the setting of NB-ultraviolet-B (UVB) therapy is
      debatable. It may be clarified through a comparative assessment between crude
      coal tar and petrolatum as pretreatment candidates. METHODS: A prospective study
      included 40 patients with plaque psoriasis undergoing NB-UVB therapy. We compared
      among three treatment regimens: NB-UVB alone (control group; n=20) as well as NB
      UVB preceded by crude coal tar 3% on one side and petrolatum on the other side
      (cases group I and II; n=20). Tar and petrolatum were topically applied
      thrice/day the day before NB-UVB exposure. Applications were removed using olive
      oil directly before NB-UVB exposure. Regimens' frequency was thrice/week and the
      clinical outcome was assessed, through both psoriasis area and severity index
      (PASI) and physician global assessment (PGA) scores, at baseline and 3 months
      later. RESULTS: There were significant (P<0.01) decreases in both PASI and PGA
      scores in all the groups. In comparison with the controls, cases revealed
      significantly (P<0.05) higher improvement percentages in both PASI and PGA scores
      for both tar and petrolatum. This influence, through the PGA score, was
      significantly (P<0.05) in favor of petrolatum. CONCLUSION: The pretreatment of
      psoriatic plaques with either petrolatum or crude coal tar may enhance the
      therapeutic outcome of NB-UVB, which appeared to favor petrolatum.

PMID- 21950626
TI  - Protection against ultraviolet A-induced oxidative damage in normal human
      epidermal keratinocytes under post-menopausal conditions by an ultraviolet A
      activated caged-iron chelator: a pilot study.
AB  - BACKGROUND/PURPOSE: Human skin is constantly exposed to ultraviolet A (UVA),
      which can generate reactive oxygen species and cause iron release from ferritin,
      leading to oxidative damage in biomolecules. This is particularly true in post
      menopausal skin due to an increase in iron as a result of menopause. As iron is
      generally released through desquamation, the skin becomes a main portal for the
      release of excess iron in this age group. In the present study, we examined a
      strategy for controlling UVA- and iron-induced oxidative stress in skin using a
      keratinocyte post-menopausal cellular model system. METHODS: Keratinocytes that
      had been cultured under normal or high-iron, low-estrogen conditions were treated
      with (2-nitrophenyl) ethyl pyridoxal isonicotinoyl hydrazone (2-PNE-PIH). 2-PNE
      PIH is a caged-iron chelator that does not normally bind iron but can be
      activated by UVA radiation to bind iron. Following incubation with 2-PNE-PIH, the
      cells were exposed to 5 J/cm2 UVA and then measured for changes in lipid
      peroxidation and ferritin levels. RESULTS: 2-PNE-PIH protected keratinocytes
      against UVA-induced lipid peroxidation and ferritin depletion. Further, 2-PNE-PIH
      was neither cytotoxic nor did it alter iron metabolism. CONCLUSION: 2-PNE-PIH may
      be a useful deterrent against UVA-induced oxidative stress in post-menopausal
      women.

PMID- 21950627
TI  - The solar ultraviolet B radiation protection provided by shading devices with
      regard to its diffuse component.
AB  - BACKGROUND: The composition of the incident solar global ultraviolet B (UVB)
      radiation with regard to its beam and diffuse radiation fractions is highly
      relevant with regard to outdoor sun protection. This is especially true with
      respect to sun protection during leisure-time outdoor sun exposure at the shore
      and pools, where people tend to escape the sun under shade trees or different
      types of shading devices, e.g., umbrellas, overhangs, etc., believing they offer
      protection from the erythemal solar radiation. The degree of sun protection
      offered by such devices is directly related to the composition of the solar
      global UVB radiation, i.e., its beam and diffuse fractions. METHODS: The
      composition of the incident solar global UVB radiation can be determined by
      measuring the global UVB (using Solar Light Co. Inc., Model 501A UV-Biometer) and
      either of its components. The beam component of the UVB radiation was determined
      by measuring the normal incidence beam radiation using a prototype, tracking
      instrument consisting of a Solar Light Co. Inc. Model 501A UV-Biometer mounted on
      an Eppley Solar Tracker Model St-1. The horizontal beam component of the global
      UVB radiation was calculated from the measured normal incidence using a simple
      geometric correlation and the diffuse component is determined as the difference
      between global and horizontal beam radiations. RESULTS: Horizontal and vertical
      surfaces positioned under a horizontal overhang/sunshade or an umbrella are not
      fully protected from exposure to solar global UVB radiation. They can receive a
      significant fraction of the UVB radiation, depending on their location beneath
      the shading device, the umbrella radius and the albedo (reflectance) of the
      surrounding ground surface in the case of a vertical surface. CONCLUSIONS:
      Shading devices such as an umbrella or horizontal overhang/shade provide relief
      from the solar global radiation and do block the solar global UVB radiation to
      some extent; nevertheless, a significant fraction of the solar global UVB
      radiation does penetrate this supposedly 'protective or comfort zone'. As a
      result, it is imperative to either apply sunscreen or cover up the exposed body
      surfaces even when under such shading devices.

PMID- 21950628
TI  - Systemic photosensitivity due to Goji berries.
AB  - Systemic photosensitivity due to the intake of plants or herbal compounds is a
      rare phenomenon. Goji berries are widely used as a well-being and anti-aging
      remedy. In spite of this, only a few adverse reactions and no cases of
      photosensitivity have been reported to date. A 53-year-old male consulted due to
      a pruriginous eruption located on sun-exposed areas of 2 weeks of duration. He
      had been taking Goji berries and infusions of cat's claw herb for 5 and 3 months,
      respectively. Minimal erythema dose for UVB (MED-UVB) was diminished when the
      patient was taking these products, and became normal when they were withdrawn.
      Photoprovocation tests with Goji berries and cat's claw were performed. MED-UVB
      decreased after the intake of Goji berries, and was normal with cat's claw. We
      report the first case of systemic photosensitivity due to Goji berries.

PMID- 21950629
TI  - Successful treatment of psoriasis vulgaris with targeted narrow-band ultraviolet
      B therapy using a new flat-type fluorescent lamp.
AB  - Narrow-band ultraviolet B (NB-UVB) therapy is widely used for refractory skin
      diseases. Targeted phototherapy is now being used to reduce the number of
      sessions and to avoid exposing normal skin. We developed a targeted NB-UVB
      therapy using a flat-type lamp emitting a wavelength similar to that of the TL-01
      fluorescent lamp. Six Japanese patients with psoriasis were recruited and treated
      with the flat-type NB-UVB device with an initial dose of 70% of the minimal
      erythema dose, with a 20% increase at each subsequent session. The plaque
      severity score was determined. All lesions of the tested patients were responsive
      to NB-UVB therapy using the flat-type lamp. The mean percent reduction of the
      lesion was 58.3 +/- 17.7%. The mean cumulative dose was 20.8 +/- 10.8 J/cm2. No
      side effects were observed during treatment. The flat-type targeted NB-UVB device
      is compact and convenient, and highly effective for the treatment of limited
      psoriasis lesions.

PMID- 21950630
TI  - Localized bullous pemphigoid induced by photodynamic therapy.
AB  - Topical photodynamic therapy (PDT) causes localized phototoxicity and has been
      shown both in vitro and in humans to have immunomodulatory and immunosuppressive
      effects. We report a case of localized bullous pemphigoid (BP) developing after
      PDT. Although BP has been reported to develop following cutaneous insults such as
      surgery, radiotherapy, psoralen ultraviolet A (PUVA) and ultraviolet B
      phototherapy, PDT has not previously been reported as a trigger. Possible
      mechanisms include direct mechanical injury to the basement membrane and
      subsequent autoantibody formation, an indirect immunomodulatory effect of PDT, or
      most likely, precipitation of BP in individuals with pre-existing low titres of
      epidermal autoantibodies (so-called subclinical BP). PDT should be added to the
      list of possible exogenous triggers for BP and this condition should be
      considered if blistering develops following PDT.

PMID- 21950631
TI  - Successful treatment of cutaneous leishmaniasis with intralesional aminolevulinic
      acid photodynamic therapy.
AB  - Leishmaniasis is a protozoan infectious disease that often affects the skin and
      may acquire a chronic and difficult to treat course. Topical photodynamic therapy
      (PDT) is a novel treatment which involves the selective uptake of a
      photosensitizing agent. Exposure to an appropriate light source in the presence
      of oxygen leads to formation of reactive oxygen species and destruction of the
      target cells. We report on the successful treatment of a 69-year-old patient with
      a relapse of long-standing cutaneous leishmaniasis using intralesional
      aminolevulinic acid-PDT.

PMID- 21950632
TI  - The D-batable safety of sunscreens.

PMID- 21950634
TI  - Photo(chemo)therapy for vitiligo.
AB  - Vitiligo is a common skin disease characterized by loss of normal melanin
      pigments in the skin and its pathogenesis is still unclear. Treatment modalities
      include psoralen plus ultraviolet A, narrow-band ultraviolet B (NB UVB)
      phototherapy, topical and systemic steroids, topical calcineurin inhibitors,
      topical vitamin D analogues in monotherapy or in association with phototherapy,
      and surgical treatment. NB UVB (310-315 nm) radiation is now considered as the
      'gold standard' for the treatment of diffuse vitiligo, and treatment with two
      recently introduced UVB sources that emit 308 nm wavelengths, the 308 nm xenon
      chloride (XeCl) excimer laser and the 308 nm XeCl excimer light, has also been
      reported to be effective and might be the treatment of choice for localized
      disease: this treatment modality has been defined as 'targeted phototherapy.'

PMID- 21950637
TI  - The effectiveness of continuing group psychotherapy for outpatients with alcohol
      dependence: 77-month outcomes.
AB  - BACKGROUND: Group psychotherapy (PT) is one of the most common interventions used
      to treat alcohol dependence (AD), and it is assumed to be effective. Despite its
      common clinical use, long-term trials that have been conducted to examine the
      efficacy of group PT in the treatment of outpatients with AD are limited and
      often lack appropriate comparisons. On that basis, a long-term comparative trial
      was performed with the main objective of evaluating the effectiveness of
      continuing group PT for outpatients with AD. METHODS: Quasi-experimental trial
      was conducted from January 2004 to May 2010 in 177 AD subjects who had completed
      an inpatient 10-week alcohol treatment program. Abstinence rates of the combined
      group (experimental group: outpatient individual PT plus group PT, N = 94) and
      the standard outpatient individual PT-only group (comparison group, N = 83) were
      statistically compared using Kaplan-Meier survival analysis. Predictive factors
      of abstinence rate for alcohol were assessed using Cox regression analysis.
      RESULTS: Abstinence rates of the combined PT group were significantly high
      relative to those of the outpatient individual PT-only group. Significant
      predictive factors for the alcohol abstinence rate were outpatient group PT and
      age. Even after controlling for confounding factors, outpatient group PT was a
      significant predictive factor for the alcohol abstinence rate. CONCLUSIONS: Our
      findings indicate that for AD patients who had completed an inpatient 10-week
      alcohol treatment, outpatient group PT appears to be an effective form of
      continuing care or aftercare within the context of an outpatient service delivery
      system.

PMID- 21950636
TI  - The structure and function of the glucagon-like peptide-1 receptor and its
      ligands.
AB  - Glucagon-like peptide-1(7-36)amide (GLP-1) is a 30-residue peptide hormone
      released from intestinal L cells following nutrient consumption. It potentiates
      the glucose-induced secretion of insulin from pancreatic beta cells, increases
      insulin expression, inhibits beta-cell apoptosis, promotes beta-cell neogenesis,
      reduces glucagon secretion, delays gastric emptying, promotes satiety and
      increases peripheral glucose disposal. These multiple effects have generated a
      great deal of interest in the discovery of long-lasting agonists of the GLP-1
      receptor (GLP-1R) in order to treat type 2 diabetes. This review article
      summarizes the literature regarding the discovery of GLP-1 and its physiological
      functions. The structure, function and sequence-activity relationships of the
      hormone and its natural analogue exendin-4 (Ex4) are reviewed in detail. The
      current knowledge of the structure of GLP-1R, a Family B GPCR, is summarized and
      discussed, before its known interactions with the principle peptide ligands are
      described and summarized. Finally, progress in discovering non-peptide ligands of
      GLP-1R is reviewed. GLP-1 is clearly an important hormone linking nutrient
      consumption with blood sugar control, and therefore knowledge of its structure,
      function and mechanism of action is of great importance.

PMID- 21950638
TI  - Fertility suppression in male albino rats by administration of methanolic extract
      of Opuntia dillenii.
AB  - To control growing world population, there is a need for male contraceptive
      methods that are comparable to female contraceptives, but due to lack of
      knowledge or investigation, no sufficient safe and effective contraceptives were
      developed till now. In the present investigation, the effect of 100% methanol
      extract of Opuntia dillenii phylloclade on reproduction in male rats was studied.
      A first group (I) received vehicle alone to serve as control. The second group
      (II) was further divided into treated and recovery groups, and the plant extract
      at 50 mg kg body weight(-1) was administered orally for 30 days. Biochemical,
      haematological and histopathological analyses were carried out to reveal the
      effects on reproductive organs in the male rats. The weights of reproductive
      organs were recorded. It was found that the number of fertile males, number of
      inseminated females, number of litters delivered and testosterone levels were
      reduced significantly. Epididymal sperm count and motility were also
      significantly decreased. Biochemical parameters support the antifertility
      activity of O. dillenii i.e. decreases in protein, glycogen content and elevation
      in cholesterol level. Testes and sperm morphology were altered significantly.
      Haematological parameters have not shown any significant changes. It is concluded
      that 100% methanol extract of O. dillenii possesses antifertility effects on male
      reproduction without change in general physiology.

PMID- 21950639
TI  - Mapping geographic areas of high and low drug adherence in patients prescribed
      continuing treatment for acute coronary syndrome after discharge.
AB  - ABSTRACT STUDY OBJECTIVE: To determine the feasibility of using geographic
      information system (GIS) technology to identify geographic areas of high and low
      adherence to cardiovascular drug therapy for treatment of acute coronary syndrome
      (ACS) in patients discharged from a university-affiliated hospital. Design.
      Retrospective analysis. DATA SOURCE: A registry of patients admitted to and
      discharged from a large university-affiliated medical center for the treatment of
      ACS. Patients. A total of 1081 adults distributed over 300 census tracts who were
      discharged between April 1999 and December 2004 with a diagnosis of an ACS event
      of unstable angina or acute myocardial infarction. MEASUREMENTS AND MAIN RESULTS:
      Data were collected on patient demographics, home addresses, and adherence to
      four classes of drugs - statins, angiotensin-converting enzyme inhibitors, beta
      blockers, and aspirin - at 6-12 months after discharge for the ACS index event. A
      GIS program was used to map patient addresses and adherence data to geographic
      coordinates. Hot Spot Analysis was used to determine the existence of any spatial
      clustering patterns in adherence rates. The analysis was performed at the census
      tract level by using the percentage of nonadherent patients within a census tract
      to represent adherence for the people living within that tract, standardized by
      the number of residents in a census tract aged 40 years or older. Hot Spot
      Analysis identified unique geographic areas of high, neutral, and low adherence
      in the southeast area. Highly adherent census tracts were primarily located in
      and around the city where the university hospital and clinics are located. Areas
      of low adherence were located to the west, southwest, and southeast of the city.
      All other census tracts were considered neutral in adherence rates. CONCLUSION:
      Mapping geographic areas of drug adherence is feasible with use of GIS
      technology, with spatial mapping able to detect areas of varying levels of
      adherence. Future research should examine local-level factors associated with low
      adherence, which can be used to derive tailored, locally relevant interventions
      to improve long-term drug adherence.

PMID- 21950640
TI  - Steady-state pharmacokinetics of intravenous levetiracetam in neurocritical care
      patients.
AB  - STUDY OBJECTIVES: To characterize the steady-state pharmacokinetics of
      intravenous levetiracetam in neurocritical care patients requiring seizure
      prophylaxis after a neurologic injury and to determine which dosing regimens
      achieve serum concentrations within the recommended therapeutic range of 6-20
      MUg/ml. DESIGN. Prospective, open-label, steady-state pharmacokinetic study.
      SETTING: Neurocritical care unit in a tertiary care medical center. PATIENTS.
      Twelve adults (five men, seven women) admitted to the neurocritical care unit who
      required prophylactic anticonvulsant therapy after subarachnoid hemorrhage,
      subdural hematoma, or traumatic brain injury. INTERVENTION: Patients received an
      intravenous infusion of levetiracetam 500 mg over 15 minutes every 12 hours.
      MEASUREMENTS AND MAIN RESULTS: Serial blood samples were collected from all
      patients after a minimum of four doses of therapy. Serum levetiracetam
      concentrations were determined by ultraperformance liquid chromatography with
      tandem mass spectrometry detection, and pharmacokinetic data were analyzed by
      compartmental and noncompartmental methods. Monte Carlo simulations were
      performed for multiple levetiracetam dosing regimens to determine the probability
      of achieving a target trough concentration of 6 MUg/ml or greater, 20 MUg/ml or
      greater, and 6-20 MUg/ml. The mean +/- SD levetiracetam maximum serum
      concentration was 28.0 +/- 8.0 MUg/ml, minimum serum concentration 3.1 +/- 1.8
      MUg/ml, half-life 5.2 +/- 1.2 hours, systemic clearance 5.6 +/- 1.8 L/hour, and
      volume of distribution at steady state 36.8 +/- 6.3 L. Increasing the doses of
      levetiracetam increased the probability of achieving a target trough
      concentration of 6 MUg/ml or greater but also increased the probability of
      achieving trough concentrations greater than 20 MUg/ml. Levetiracetam doses of
      1000 mg every 8 hours and 1500-2000 mg every 12 hours provided the highest
      probability of achieving a target trough concentration between 6 and 20 MUg/ml.
      CONCLUSION: Compared with previously published results in healthy volunteers and
      adults in status epilepticus, levetiracetam systemic clearance was faster and the
      terminal elimination half-life was shorter in neurocritical care patients. Higher
      doses or more frequent dosing may be needed to achieve target trough
      concentrations of 6-20 MUg/ml.

PMID- 21950641
TI  - Effect of cytochrome P450 3A5 genotype on atorvastatin pharmacokinetics and its
      interaction with clarithromycin.
AB  - Abstract Study Objective. To assess the effects of the cytochrome P450 (CYP) 3A
      genotype, CYP3A5, on atorvastatin pharmacokinetics and its interaction with
      clarithromycin. Design. Prospective, two-phase, randomized-sequence, open-label
      pharmacokinetic study. Setting. Clinical research center at a teaching hospital.
      Subjects. Twenty-three healthy volunteers who were screened for genotype: 10
      subjects carried the CYP3A5*1 allele (expressors) and 13 subjects did not
      (nonexpressors). Intervention. In one phase, subjects received a single oral dose
      of atorvastatin 20 mg. In the other phase, subjects received clarithromycin 500
      mg twice/day for 5 days; on day 4 after the morning dose, subjects also received
      a single oral dose of atorvastatin 20 mg. All subjects participated in both
      phases of the study, which were separated by at least 14 days. Measurements and
      Main Results. Pharmacokinetic parameters of both forms of atorvastatin
      atorvastatin acid and atorvastatin lactone-were compared between CYP3A5
      expressors and nonexpressors, both in the absence and presence of clarithromycin,
      a strong CYP3A inhibitor. The acid form is pharmacologically active, and the
      lactone form has been associated with the atorvastatin's muscle-related adverse
      effects. Atorvastatin acid exposure did not differ significantly between CYP3A5
      genotype groups. When subjects had not received clarithromycin pretreatment, the
      area under the concentration-time curve from time zero extrapolated to infinity
      (AUC(0-infinity)) of atorvastatin lactone was 36% higher in nonexpressors than in
      expressors (median 47.6 ng*hr/ml [interquartile range (IQR) 37.8-64.3 ng*hr/ml]
      vs 34.9 ng*hr/ml [IQR 21.6-42.2 ng*hr/ml], p=0.038). After clarithromycin
      pretreatment, changes in the pharmacokinetic parameters of atorvastatin acid and
      lactone were not significantly different between the nonexpressors versus the
      expressors; however, the increase in the AUC(0-infinity) of atorvastatin lactone
      was 37% greater in expressors than in nonexpressors (geometric mean +/- SD 3.59
      +/- 0.57 vs 2.62 +/- 0.35, p=0.049). Conclusion. Our data suggest that the CYP3A5
      genotype has minimal effects on the pharmacokinetic parameters of atorvastatin
      and its interaction with clarithromycin; these effects are unlikely to be
      clinically significant.

PMID- 21950642
TI  - Telaprevir: a novel NS3/4 protease inhibitor for the treatment of hepatitis C.
AB  - Hepatitis C virus (HCV) infection affects millions of people worldwide; however,
      standard therapy with peginterferon and ribavirin has resulted in suboptimal
      responses. Thus, new anti-HCV drugs with novel mechanisms of action are being
      studied. In particular, new drugs are being developed that target the NS3/4A
      protease complex. We evaluated the literature on telaprevir, a new, oral,
      covalent, reversible NS3/4A HCV protease inhibitor. A MEDLINE search (January
      1996-July 2011) was performed to identify relevant clinical trials, and abstracts
      from hepatology and human immunodeficiency virus (HIV) conferences were reviewed.
      In large clinical trials, the addition of telaprevir to peginterferon and
      ribavirin resulted in high sustained virologic response rates in both treatment
      naive and treatment-experienced patients infected with HCV genotype 1. Clinical
      data with telaprevir in the HIV-HCV coinfected population are emerging, as well
      as data on potential drug-drug interactions with this agent. Preliminary data
      describe the resistance profile of telaprevir; however, more information is
      needed in this evolving area. Telaprevir's most common adverse events included
      rash, pruritis, and anemia. Based on available data, this new anti-HCV drug will
      likely be widely used and may revolutionize the treatment of HCV-infected
      individuals.

PMID- 21950643
TI  - New and emerging anticoagulant therapy for atrial fibrillation and acute coronary
      syndrome.
AB  - Abstract   Thrombosis is an underlying cause of many cardiovascular disorders,
      and generation of thrombi in the arterial circulation can lead to unstable
      angina, myocardial infarction, or ischemic stroke. Antithrombotic therapy is
      widely used, with proven benefit to prevent ischemic stroke and thromboembolic
      events in patients with atrial fibrillation (AF) or to prevent further ischemic
      complications in patients with acute coronary syndrome (ACS). Traditional
      anticoagulants (including unfractionated heparin, low-molecular-weight heparin,
      and warfarin) and antiplatelet agents (including aspirin, clopidogrel, and
      prasugrel) are typically used for these indications. Limitations to their use
      include variable pharmacokinetic and pharmacodynamic profiles, inability to
      inhibit fibrin-bound thrombin, risk of heparin-induced thrombocytopenia, delayed
      onset of action, numerous drug interactions, need for substantial laboratory
      monitoring and dosage titrations, hyporesponsiveness or resistance,
      hypersensitivity, adverse events, and bleeding. To overcome some of the
      limitations of traditional agents, new antithrombotic agents under development
      are highly selective for specific coagulation factors blocking the synthesis of
      thrombin. Clinicians must have an understanding of the new anticoagulants to aid
      in the selection of appropriate therapies for patients. We describe the most
      relevant phases II and III clinical trials that evaluated several recent emerging
      anticoagulant drugs for use in patients with AF or ACS. The advantages of many
      new agents include predictable pharmaco-dynamic response and pharmacokinetic
      parameters, allowing for fixed oral dosing with no need for laboratory
      monitoring. For patients with AF, dabigatran is already approved for the
      prevention of stroke and systemic embolism, rivaroxaban appears to be an
      effective alternative to warfarin in high-risk patients, and apixaban may also be
      an effective alternative to aspirin in patients unable to take warfarin.
      Otamixaban shows promise as an intravenous alternative for patients with ACS in
      the acute care setting. Likewise, rivaroxaban, dabigatran, and darexaban with or
      without dual antiplatelet therapy may be beneficial for secondary prevention of
      ischemic events in patients with ACS.

PMID- 21950644
TI  - Adjunct mirtazapine for negative symptoms of schizophrenia.
AB  - Negative symptoms of schizophrenia are characterized by affective flattening,
      alogia, avolition, and anhedonia and are often nonresponsive to antipsychotic
      therapy. Because negative symptoms are predictive of poor occupational and social
      functioning, as well as poor global outcomes, numerous studies evaluating adjunct
      therapy to antipsychotics have been conducted. This review focuses on the use of
      the antidepressant mirtazapine as adjunct therapy to antipsychotics for the
      treatment of negative symptoms of schizophrenia. A literature search of the
      MEDLINE database (from inception-March 2011) identified eight relevant articles:
      six were randomized, double-blind, placebo-controlled trials, and two were open
      label trials. Of the six randomized trials reviewed, four studies assessed add-on
      mirtazapine to second-generation antipsychotics, whereas two studies examined add
      on mirtazapine to first-generation antipsychotics. Five of the six randomized
      trials supported the use of mirtazapine for negative symptoms of schizophrenia.
      Of the two open-label trials, one naturalistic study demonstrated that
      mirtazapine add-on therapy to clozapine was not associated with improvements in
      negative symptoms; however, this study focused primarily on improvements in
      cognition, not negative symptoms. An open-label extension phase to a randomized
      controlled trial showed that mirtazapine continued to produce significant
      improvement in negative symptoms over a longer duration of time, when added to
      first-generation antipsychotic therapy. Overall, mirtazapine appears to be well
      tolerated and associated with few drug interactions. Although adjunct mirtazapine
      to antipsychotics has been shown to be effective at doses of 30 mg/day in most of
      the trials, limitations of these studies include short study duration and small
      sample sizes. To improve generalizability, larger multicenter studies with
      broader inclusion criteria should be conducted. In addition, studies of longer
      duration that use different mirtazapine dosages are needed to further assess the
      benefits of mirtazapine for negative symptoms of schizophrenia.

PMID- 21950645
TI  - Efficacy, safety, and cost of thrombolytic agents for the management of
      dysfunctional hemodialysis catheters: a systematic review.
AB  - Approximately 100,000 patients begin hemodialysis each year in the United States.
      Although an arteriovenous fistula or graft is the preferred method for long-term
      vascular access during hemodialysis, as these types of vascular access are the
      most reliable, approximately 30% of patients require the use of catheters to
      continue hemodialysis. Tunneled, cuffed hemodialysis catheters are discouraged
      for permanent vascular access because of their high rates of infection, morbidity
      and mortality, and thrombotic and technical complications. These catheters have a
      short functional life span and require medical intervention, often thrombolytic
      therapy, to treat the catheter malfunction. No thrombolytic agent is specifically
      indicated for the management of occluded hemodialysis catheters. Thus, we
      performed a systematic review to critically evaluate all available studies that
      examined the efficacy, safety, and cost of thrombolytic therapy for the
      management of dysfunctional hemodialysis catheters. Studies were included if they
      reported efficacy in a specific proportion of affected dysfunctional hemodialysis
      catheters; reported the proportion of patients experiencing an adverse outcome
      (especially bleeding); and described the type of catheter used, dose of
      thrombolytic agent, administration protocol, dwell time, definition of treatment
      success, time to follow-up for study end points, and sample size. Eighteen
      studies met the inclusion criteria. The mean +/- SD success rate in clearing
      dysfunctional hemodialysis catheters was greatest with reteplase at 88 +/- 4%,
      followed by alteplase at 81 +/- 37% and tenecteplase at 41 +/- 5%. Adverse
      effects associated with the use of these thrombolytic agents administered at low
      doses were extremely rare. No serious adverse bleeding events attributed to
      thrombolytic therapy were reported in any of the trials. Aliquotted reteplase
      from vials for intravenous use was the least costly thrombolytic agent. Thus, at
      centers that use high volumes of thrombolytics for dysfunctional hemodialysis
      catheters, reteplase is the thrombolytic agent of choice.

PMID- 21950650
TI  - Relation between duration and severity in bereavement-related depression.
AB  - OBJECTIVE: Prolonged duration is commonly used as an indicator that bereavement
      related depression (BRD) is pathological. DSM-IV replaced the traditional 1-year
      pathology cut-point by a 2-month cut-point. Yet, little evidence exists regarding
      the validity of these cut-points in indicating increased BRD severity. This study
      evaluated the validity of the 2-month and 1-year cut-points in differentiating
      less severe from more severe BRDs in a nationally representative U.S. sample.
      METHOD: National Comorbidity Survey respondents with BRD's (n = 152) lasting 0-8,
      9-52 and >52 weeks were evaluated for depression severity using six severity
      indicators. Cut-point validity was established by discontinuities in severity
      levels between durations below and above the cut-point. RESULTS: Bereavement
      related depressions of >52-week duration were significantly higher than 9- to 52
      week BRDs on four of six severity indicators and on a cumulative overall severity
      measure of mean number of severity indicators per person, whereas <=8-week and 9-
      to 52-week durational categories differed on one severity indicator and not on
      overall severity. Additional analyses using durations 0-12, 13-26, 27-52 and >52
      weeks suggested that alternative <52-week cut-points also lack validity.
      CONCLUSION: The traditional 1-year cut-point validly identifies increasing BRD
      severity; DSM's 2-month cut-point does not. Duration does not indicate increasing
      BRD severity before 1 year. Research using the 2-month cut-point may yield
      misleading results.

PMID- 21950651
TI  - Anti-inflammatory activities of selected synthetic homoisoflavanones.
AB  - Four homoisoflavanones of the 3-benzylidene-4-chromanone type, some of which were
      previously isolated from Caesalpinia pulcherrima, were synthesised to determine
      their anti-inflammatory activity and cytotoxicity. A range of four different
      homoisoflavanones (compounds 4a-4d) were synthesised from the corresponding
      substituted phenols. 1H- and 13C-NMR data together with high-resolution mass
      spectroscopy data were employed to elucidate the structures. Anti-inflammatory
      activity was determined in mice with acute croton oil-induced auricular
      dermatitis. In vitro cytotoxicity was tested against a Chinese hamster ovarian
      cell line using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide
      (MTT) assay. Compound 4a exhibited a tendency to inhibit oedema in a dose
      dependent manner after 3 and 6 h of treatment. Compounds 4b-4d also inhibited
      oedema, although a clear dose-response relationship was not observed. Compounds
      4a-4c were found to be less cytotoxic than compound 4d. Compound 4b was the least
      cytotoxic. Compounds 4a-4d exhibited anti-inflammatory activity and varying
      levels of cytotoxicity.

PMID- 21950652
TI  - Enhanced transport of colloidal oil droplets in saturated and unsaturated sand
      columns.
AB  - Colloidal-sized triacylglycerol droplets demonstrated enhanced transport compared
      to ideal latex colloid spheres in both saturated and unsaturated quartz sand
      columns. Oil droplets (mean diameter 0.74 +/- 0.03 MUm, density 0.92 g cm(-3),
      zeta-potential -34 +/- 1 mV) were injected simultaneously with latex microsphere
      colloids (FluoSpheres; density 1.055 g cm(-3), diameters 0.02, 0.2, and 1.0 MUm,
      zeta-potentials -16 +/- 1, -30 +/- 2, and -49 +/- 1, respectively) and bromide
      into natural quartz sand (zeta-potential -63 +/- 2 mV) via short-pulse column
      breakthrough experiments. Tests were conducted under both saturated and
      unsaturated conditions. Breakthrough of oil droplets preceded bromide and
      FluoSpheres. Recovery of oil droplets was 20% greater than similarly sized
      FluoSpheres in the saturated column, and 16% greater in the 0.18 +/- 0.01
      volumetric water content (VWC) unsaturated column. Higher variability was
      observed in the 0.14 +/- 0.01 VWC column experiments with oil droplet recovery
      only slightly greater than similarly sized FluoSpheres. The research presents for
      the first time the direct comparison of colloidal oil droplet transport in porous
      media with that of other colloids, and demonstrates transport under unsaturated
      conditions. Based on experimental results and theoretical analyses, we discuss
      possible mechanisms that lead to the observed enhanced mobility of oil droplets
      compared to FluoSpheres with similar size and electrostatic properties.

PMID- 21950653
TI  - Increases in muscle blood flow after a mixed meal are impaired at all stages of
      type 2 diabetes.
AB  - OBJECTIVE: In type 2 diabetes, although the impairment of postprandial muscle
      blood flow response is well established, information on the effect of this
      impairment on glucose uptake and lipid metabolism is controversial. DESIGN:
      Postprandial forearm blood flow responses and metabolic parameters were assessed
      in a cross-sectional study of subjects at various stages of insulin resistance.
      PATIENTS: Eleven healthy subjects (CONTROLS), 11 first-degree relatives of type-2
      diabetics (RELATIVES), 10 patients with impaired glucose tolerance (IGT), 10
      diabetic patients with postprandial hyperglycaemia (DMA), and 13 diabetic
      patients with both fasting and postprandial hyperglycaemia (DMB). MEASUREMENTS:
      All subjects received a meal. Blood was drawn from a forearm deep vein and the
      radial artery at specific time-points during a period of 360 min for measurements
      of glucose, insulin, triglycerides and nonesterified-fatty acids. Forearm muscle
      blood flow was measured with strain-gauge plethysmography. Glucose uptake and ISI
      Index were calculated. RESULTS: Peak-baseline muscle blood flow was higher in
      CONTROLS (3.32 +/- 0.4) than in RELATIVES (0.53 +/- 0.29), IGT (0.82 +/- 0.2),
      DMA (1.44 +/- 0.34), DMB (1.23 +/- 0.35 ml/min/100 ml tissue), P < 0.001. Glucose
      uptake (AUC(0-360,) MUmol/100 ml tissue) was higher in CONTROLS (1023 +/- 132)
      than in RELATIVES (488 +/- 42), IGT (458 +/- 43), DMA (347 +/- 63), DMB (543 +/-
      53), P < 0.001. ISI index, postprandial triglycerides and nonesterified-fatty
      acids behaved in a similar way. Peak-baseline muscle blood flow correlated
      positively with glucose uptake (r = 0.440, P = 0.001) and ISI index (r = 0.397, P
      = 0.003), and negatively with postprandial triglycerides (r = -0.434, P = 0.001)
      and nonesterified-fatty acids (r = -0.370, P = 0.005). CONCLUSIONS: These results
      suggest that increase in muscle blood flow after a meal is impaired at all stages
      of type-2 diabetes. This defect influences glucose uptake and is associated with
      impaired lipid metabolism in the postprandial state.

PMID- 21950654
TI  - Chronic antagonism of the mineralocorticoid receptor ameliorates hypertension and
      end organ damage in a rodent model of salt-sensitive hypertension.
AB  - We investigated the effects of chronic mineralocorticoid receptor blockade with
      eplerenone on the development and progression of hypertension and end organ
      damage in Dahl salt-sensitive rats. Eplerenone significantly attenuated the
      progressive rise in systolic blood pressure (SBP) (204 +/- 3 vs. 179+/-3 mmHg, p
      < 0.05), reduced proteinuria (605.5 +/- 29.6 vs. 479.7 +/- 26.1 mg/24h, p <
      0.05), improved injury scores of glomeruli, tubules, renal interstitium, and
      vasculature in Dahl salt-sensitive rats fed a high-salt diet. These results
      demonstrate that mineralocorticoid receptor antagonism provides target organ
      protection and attenuates the development of elevated blood pressure (BP) in a
      model of salt-sensitive hypertension.

PMID- 21950655
TI  - Evaluation of the impact of nurse consultant roles in the United Kingdom: a mixed
      method systematic literature review.
AB  - AIM: This paper reports a mixed methods systematic review examining the impact of
      nurse consultant roles in adult healthcare settings, with a view to identifying
      indicators for demonstrating their impact on patient and professional outcomes.
      BACKGROUND: Nurse consultants were introduced in England in 2000 with the
      intention to achieve better outcomes for patients by improving quality and
      services. Previous studies have investigated the impact of nurse consultants, but
      attempts to amalgamate this evidence have been methodologically limited. Since
      these reviews were published, the importance of demonstrating the contribution of
      nurse consultants has prompted new research. A robust review of the evidence is
      now required. DATA SOURCES: A broad search strategy was adapted for eight
      databases. Grey literature was sought from various sources. REVIEW METHODS:
      Quantitative and qualitative studies were included. Study quality was assessed
      using appropriate instruments. Cross-study synthesis combined the quantitative
      and qualitative findings in relation to the dimensions of impact identified.
      Measures of impact were mapped against a framework for assessing clinical and
      professional outcomes. RESULTS: Thirty-six studies were included. The findings
      suggest a largely positive influence of nurse consultants on a range of clinical
      and professional outcomes, which map onto the proposed framework of impact.
      However, there was very little robust evidence and the methodological quality of
      studies was often weak. CONCLUSION: Further robust research is required to
      explore nurse consultants' impact on patient and professional outcomes. The
      proposed framework for assessing impact could be used to guide future research
      and assist nurse consultants assess their impact.

PMID- 21950656
TI  - Structure determination and interception of biosynthetic intermediates for the
      plantazolicin class of highly discriminating antibiotics.
AB  - The soil-dwelling, plant growth-promoting bacterium Bacillus amyloliquefaciens
      FZB42 is a prolific producer of complex natural products. Recently, a new FZB42
      metabolite, plantazolicin (PZN), has been described as a member of the growing
      thiazole/oxazole-modified microcin (TOMM) family. TOMMs are biosynthesized from
      inactive, ribosomal peptides and undergo a series of cyclodehydrations,
      dehydrogenations, and other modifications to become bioactive natural products.
      Using high-resolution mass spectrometry, chemoselective modification, genetic
      interruptions, and other spectroscopic tools, we have determined the molecular
      structure of PZN. In addition to two conjugated polyazole moieties, the amino
      terminus of PZN has been modified to N(alpha),N(alpha)-dimethylarginine. PZN
      exhibited a highly selective antibiotic activity toward Bacillus anthracis, but
      no other tested human pathogen. By altering oxygenation levels during
      fermentation, PZN analogues were produced that bear variability in their
      heterocycle content, which yielded insight into the order of biosynthetic events.
      Lastly, genome-mining has revealed the existence of four additional PZN-like
      biosynthetic gene clusters. Given their structural uniqueness and intriguing
      antimicrobial specificity, the PZN class of antibiotics may hold pharmacological
      value.

PMID- 21950657
TI  - Discovery of 2-(4-methylfuran-2(5H)-ylidene)malononitrile and thieno[3,2
      b]thiophene-2-carboxylic acid derivatives as G protein-coupled receptor 35
      (GPR35) agonists.
AB  - Screening with dynamic mass redistribution (DMR) assays in a native cell line HT
      29 led to identification of two novel series of chemical compounds, 2-(4
      methylfuran-2(5H)-ylidene)malononitrile and thieno[3,2-b]thiophene-2-carboxylic
      acid derivatives, as GPR35 agonists. Of these, 2-(3-cyano-5-(3,4-dichlorophenyl)
      4,5-dimethylfuran-2(5H)-ylidene)malononitrile (YE120) and 6-bromo-3
      methylthieno[3,2-b]thiophene-2-carboxylic acid (YE210) were found to be the two
      most potent GPR35 agonists with an EC(50) of 32.5 +/- 1.7 nM and 63.7 +/- 4.1 nM,
      respectively. Both agonists exhibited better potency than that of zaprinast, a
      known GPR35 agonist. DMR antagonist assays, knockdown of GPR35 with interference
      RNA, receptor internalization assays, and Tango beta-arrestin translocation
      assays confirmed that the agonist activity of these ligands is specific to GPR35.
      The present study provides novel chemical series as a starting point for further
      investigations of GPR35 biology and pharmacology.

PMID- 21950658
TI  - Regio- and stereoselective multisubstituted enol ester synthesis.
AB  - Regio- and stereoselective cohalogenation of alkynes with NXS (X = Br, I) was
      achieved, and the stereoselectivity of the resulting alkenes was dependent on the
      substituent on the alkyne. Cohalogenation and successive cross-coupling gave
      multisubstituted enol esters in a one-pot process.

PMID- 21950659
TI  - Effectiveness of intralesional meglumine antimoniate in the treatment of mucosal
      leishmaniasis of the Old World.

PMID- 21950660
TI  - Caesarean section: impact on mother and child.
AB  - Maternal/foetal morbidity/mortality consequent to uterine rupture, placenta
      previa/increta and stillbirth may occur in repeat caesarean section (CS).
      Elective CS before 39 weeks increases respiratory complications, hypoglycaemia,
      sepsis and intensive care unit admissions. Different gut colonization in neonates
      born by CS accounts for increased incidence of food allergy, asthma and possibly
      type 1 diabetes. Epigenetic changes might be responsible - among others - for
      childhood malignancies. CONCLUSION: Decision for primary CS should take into
      consideration possible maternal/neonatal complications.

PMID- 21950671
TI  - Multiple nuchal fibromas in a 2-year-old without Gardner syndrome.
AB  - Nuchal fibromas, uncommon benign soft tissue tumors typically arising along the
      posterior neck, are often associated with Gardner syndrome (GS). These tumors
      have rarely been reported in association with scleroderma or as secondary to
      trauma and diabetes. Nuchal fibromas not associated with GS have been described
      predominantly in men aged 30 to 50. We report a 2-year-old African American girl
      with multiple nuchal fibromas along the posterior aspect of her neck and upper
      back. Retinal examination showed no signs of congenital hypertrophy of the
      retinal pigment epithelium, and genetic testing for the adenomatous polyposis
      coli gene mutation seen in GS was negative.

PMID- 21950673
TI  - Drug fever due to S-carboxymethyl-L-cystein: demonstration of a causative agent
      with patch tests.

PMID- 21950672
TI  - Catalytic mechanism and roles of Arg197 and Thr183 in the Staphylococcus aureus
      sortase A enzyme.
AB  - The sortase A enzyme, which catalyzes the peptidoglycan cell wall anchoring
      reaction of LPXTG surface proteins, has been proposed to be a universal target
      for therapeutic agents against Gram-positive bacteria. The catalytic mechanism of
      the Staphylococcus aureus sortase A enzyme has been systematically studied using
      molecular dynamics simulations, ONIOM(DFT:MM) calculations, and QM/MM charge
      deletion analysis. The catalytic roles of Arg197 and Thr183 were analyzed. Our
      calculations show that Arg197 has several important roles in the mechanism. It is
      crucial for substrate binding, and is capable of reversible shift of its hydrogen
      bonds between the LP and TG carbonyls of the LPXTG substrate motif, depending on
      the protonation state of the catalytic Cys184-His120 dyad. Arg197 stabilizes the
      catalytic dyad in the active ion pair form but at the same time raises the
      barrier to acylation by approximately 8 kcal/mol. Thr183 is also essential for
      the catalytic reaction in that it correspondingly lowers the barrier by the same
      amount via electrostatic interactions. The catalytic mechanism proceeds via
      proton transfer from His120, followed by nucleophilic attack from the thiolate
      anion of Cys184. The data thus supports the proposed reverse protonation
      mechanism, and disproves the hypothesis of the Arg197 generating an oxyanion hole
      to stabilize the tetrahedral intermediate of the reaction.

PMID- 21950674
TI  - Effect of low oxygen tension atmosphere and maturation media supplementation on
      nuclear maturation, cortical granules migration and sperm penetration in swine in
      vitro fertilization.
AB  - The aim of this study was to evaluate the efficiency of low oxygen tension (5%
      CO(2) , 5% O(2) and 90% N(2) ) on in vitro oocyte maturation using defined media
      (0.1% polyvinyl alcohol - PVA) or 10% porcine follicular fluid (PFF)-supplemented
      media. To achieve this goal, oocytes were evaluated regarding cortical granules
      (GCs) migration, nuclear maturation and sperm penetration. Oocytes were in vitro
      matured under different conditions: 5% or 20% O(2) atmosphere and 0.1% PVA- or
      10% PFF-supplemented media and evaluated at 0 and 44 h of maturation. To evaluate
      the migration of CGs and nuclear maturation, by confocal microscopy, oocytes were
      incubated with 100 MUg of FITC-PNA/ml and 10 MUg/ml of propidium iodide. To
      address sperm penetration, after maturation, in vitro fertilization for 6 h and
      in vitro culture for 18 h, zygotes were incubated with 10 mg/ml Hoechst 33342.
      Pronuclei and polar bodies were quantified using an epifluorescence microscope.
      Atmosphere conditions did not affect the CGs migration, but media supplementation
      did. Oocytes matured in 10% PFF media had a higher percentage of CGs in the
      oocyte periphery than oocytes matured in PVA-supplemented media. However, this
      fact did not have effect on in vitro sperm penetration levels. No effect of
      atmosphere conditions and media supplementation was observed on the rates of
      metaphase II oocytes. Therefore, the use of low oxygen tension in association
      with PVA maturation media does not improve the in vitro maturation system of
      porcine oocytes, because its use did not improve nuclear maturation, CGs
      migration and zygotes monospermic rates.

PMID- 21950676
TI  - When is susceptibility to infections abnormal?

PMID- 21950677
TI  - Validity of the Pediatric Asthma Quality of Life Questionnaire in Polish
      children.
AB  - BACKGROUND: Although the Pediatric Asthma Quality of Life Questionnaire (PAQLQ)
      was translated for use in Polish asthmatic children, it is necessary to confirm
      that its validity, reliability, and the accuracy of the responses are not
      influenced by culture difference. Therefore, the objective of this study was to
      validate the Polish version of the Pediatric Asthma Quality of Life
      Questionnaire. METHODS: This was a 9-week period cohort study. The patients were
      interviewed using the PAQLQ on four occasions: at baseline, 1 wk after inclusion,
      and after 5 and 9 wk. At each clinic visit, lung functions test and NO
      measurements were performed. Asthma control (according to GINA) was assessed
      throughout the study. RESULTS: One hundred and one patients completed the study.
      At all visits, moderate correlations (from r = -0.51 to -0.68) between all PAQLQ
      domains and the asthma diary were observed. We noticed a significant improvement
      in the understanding of the questions during the last visit compared to baseline.
      The gradient of correlation coefficients between the symptoms domain of PAQLQ and
      asthma diary was observed across study visits. The standards of reliability
      defined by Cronbach's alpha-coefficient (from 0.75 to 0.91) were fulfilled in all
      domains of the questionnaire, at all visits. We found a higher increase in PAQLQ
      score in patients who obtained asthma control compared to those who lost control
      during the study. There was no relation between PAQLQ and FeNO. At all visits,
      moderate correlations (from r = -0.51 to -0.68) were shown between all PAQLQ
      domains and the asthma diary. CONCLUSIONS: We showed that Polish version of PAQLQ
      is valid and reliable among our study group. Moreover, as far as clinical
      practice is concerned, PAQLQ seems to be a useful tool for monitoring asthma in
      children especially based on the physician's grading of asthma severity according
      to GINA guidelines.

PMID- 21950678
TI  - Development and validation of a nighttime sleep diary in asthmatic children.
AB  - The aim of this study was to derive a shorter version of the asthma diary, 'a
      nighttime sleep diary' from the traditional asthma diary (original version). The
      nighttime sleep diary mainly consisted of nighttime awakening that met the
      criteria of validity and practicality necessary for monitoring clinical control
      in infants and young children with asthma symptoms. Validation of the diary was
      performed in a 6-week prospective study of 40 children aged 6 months to 6 years
      treated with nebulized budesonide inhalation suspension or cromolyn sodium
      nebulized solution. The nighttime awakening score was significantly and
      positively associated with the nighttime asthma symptom score and daytime asthma
      symptom score along with the number of days with a cough. Therefore, the
      nighttime sleep diary is a simple and useful instrument to monitor day-to-day
      fluctuations in young children with asthma.

PMID- 21950679
TI  - The association of maternal prenatal IgE and eczema in offspring is restricted to
      non-atopic mothers.
AB  - The risk of developing eczema is thought to be influenced by both genetic and
      environmental factors. Prenatal factors including the intrauterine environment
      may influence risk. We examined the relationship of maternal total IgE obtained
      during pregnancy to the incidence of atopic dermatitis in their 2-yr-old
      offspring. Subjects were participants in an unselected Detroit area birth cohort.
      Serum IgE was measured from 458 mothers in the third trimester of pregnancy along
      with prenatal family and environmental histories. Children were evaluated at
      approximately 2 yr of age for current or past eczema by maternal questionnaire
      and physician examination. Among the 458 children, 20.3% (n = 93) had a doctor
      confirmed diagnosis of eczema. Prenatal IgE was higher among women whose children
      developed AD vs. women whose children did not [Geometric means and 95% confidence
      intervals 52.7 IU/ml (40.9-68.0) vs. 32.9 IU/ml (28.0-38.7), p = 0.010]. The
      association was only seen in a subgroup of 181 women without allergic
      sensitization (specific IgE >0.35 IU/ml) to a panel of eight common allergens. Of
      the women without allergic sensitization, the mean serum IgE was 24.1 IU/ml (15.5
      37.6) among those whose children had a diagnosis of eczema. The mean serum IgE
      was 11.2 IU/ml (9.2-13.6) among those whose children did not have a diagnosis of
      eczema (p-value 0.002). Maternal prenatal IgE level among women who are not
      sensitized to common allergens is associated with increased risk of eczema in
      offspring.

PMID- 21950680
TI  - Pediatric allergy and immunology in Spain.
AB  - The data of the ISAAC project in Spain show a prevalence of childhood asthma
      ranging from 7.1% to 15.3%, with regional differences; a higher prevalence, 22.6%
      to 35.8%, is described for rhinitis, and atopic dermatitis is found in 4.1% to
      7.6% of children. The prevalence of food allergy is 3%. All children in Spain
      have the right to be visited in the National Health System. The medical care at
      the primary level is provided by pediatricians, who have obtained their titles
      through a 4-yr medical residency training program. The education on pediatric
      allergy during that period is not compulsory and thus very variable. There are
      currently 112 certified European pediatric allergists in Spain, who have obtained
      the accreditation of the European Union of Medical Specialist for proven skills
      and experience in pediatric allergy. Future specialists in pediatric allergy
      should obtain their titles through a specific education program to be developed
      in one of the four accredited training units on pediatric allergy, after
      obtaining the title on pediatrics. The Spanish Society of Pediatric Allergy and
      Clinical Immunology (SEICAP) gathers over 350 pediatric allergists and
      pediatricians working in this field. SEICAP has a growing activity including
      yearly congresses, continued education courses, elaboration of technical clinical
      documents and protocols, education of patients, and collaboration with other
      scientific societies and associations of patients. The official journal of SEICAP
      is Allergologia et Immunophatologia, published every 2 months since 1972. The web
      site of SEICAP, http://www.seicap.es, open since 2004, offers information for
      professionals and extensive information on pediatric allergic and immunologic
      disorders for the lay public; the web site is receiving 750 daily visits during
      2011. The pediatric allergy units are very active in clinical work, procedures as
      immunotherapy or induction of oral tolerance in food allergy, contribution to
      scientific literature, and collaboration in international projects.

PMID- 21950681
TI  - Kawasaki disease, childhood allergy and the hygiene hypothesis.

PMID- 21950683
TI  - Oxidative cyclization of 2-arylphenols to dibenzofurans under
      Pd(II)/peroxybenzoate catalysis.
AB  - 2-Arylphenols undergo intramolecular C-H bond activation/C-O bond formation to
      afford dibenzofuran derivatives under palladium catalysis in the presence of tert
      butyl peroxybenzoate as an oxidant. Kinetic isotope effect experiments indicated
      that C-H bond cleavage is the rate-limiting step of the reaction.

PMID- 21950682
TI  - Validity of HMGB1 measurement in epithelial lining fluid in patients with COPD.
AB  - BACKGROUND: It has been known that high-mobility group box 1 (HMGB1) plays an
      important role in the pathogenesis of various inflammatory disorders in the lung.
      We attempted to determine the validity of measurement of HMGB1 levels in
      epithelial lining fluid (ELF) from patients with chronic obstructive pulmonary
      disease (COPD). MATERIALS AND METHODS: We measured HMGB1 levels in ELF separately
      obtained from central or peripheral airways using a bronchoscopic microsampling
      technique in 14 non-smokers, 13 smokers without COPD and 30 smokers with COPD. We
      also evaluated whether those levels were correlated with the indexes of pulmonary
      function and grade of low-attenuation area (LAA) on high-resolution computed
      tomographic scans. RESULTS: HMGB1 levels in ELF from central airways did not
      significantly differ among the three groups. However, HMGB1 levels in peripheral
      airways were significantly higher in COPD patients than in non-smokers and
      smokers without COPD. Both the concentrations of interleukin-8 and human
      polymorphonuclear elastase in peripheral airways were also significantly higher
      in COPD patients. Moreover, those levels were significantly correlated with HMGB1
      level. In addition, HMGB1 level in peripheral airways was closely correlated with
      the degree of airflow obstruction and grade of LAA in COPD patients. CONCLUSIONS:
      HMGB1 levels in peripheral airways were elevated in smokers without COPD, as
      compared with non-smokers, and those levels were further augmented in COPD
      patients. Those levels were associated with the severity of COPD. Therefore,
      HMGB1 in peripheral airways may be a potentially interesting target for new
      pharmacological treatments in COPD patients.

PMID- 21950684
TI  - Male infertility and adult polycystic kidney disease--revisited: case report and
      current literature review.
AB  - Adult polycystic kidney disease (APKD) is one of the most common inherited
      disorders affecting one in 800-1000 live births. Extra-renal manifestation of
      APKD is not uncommon. Cysts involving the male and female reproductive system
      have been reported. However, fertility is affected only in male subjects. Among
      cysts involving the reproductive system, seminal vesicle cysts have been reported
      to be the most common. The effect of seminal vesicle cysts on male fertility has
      been controversial. Current literature reports that majority of men remain
      fertile. However, uraemia and its implications on fertility and abnormal semen
      parameters in men with seminal vesicle cysts must be taken into consideration. We
      herein present two patients with APKD with contrasting semen parameters and also
      review the current literature.

PMID- 21950685
TI  - The inhibition of eugenol on glucan is essential for the biofilm eradication
      effect on caries-related biofilm in an artificial mouth model.
AB  - This study aimed to evaluate the inhibitory effects of herbal extracts on caries
      related bacteria, glucan and biofilm in vitro. Sensitive tests of bacteria were
      carried out by broth dilution method on a 96-microwell plate. Glucan inhibition
      tests were carried out using the phenol sulphate method. A minimum biofilm
      inhibitory concentration (MBIC) test was performed in an artificial mouth model.
      The results of the MBIC of agents were 8, 16 and 32 mg mL(-1) for eugenol, tannic
      acid and magnolol, respectively. For the results of glucan inhibition tests, over
      63%, 28% and 27% inhibition occurred on insoluble glucan syntheses of
      Streptococcus sobrinus for eugenol, magnolol and tannic acid, respectively. Over
      46%, 16% and 13% inhibition on soluble glucan syntheses for eugenol, magnolol and
      tannic acid, respectively, were also observed. In conclusion, the inhibition of
      eugenol on glucan is essential for the biofilm inhibition effect on caries
      related biofilm in an artificial mouth model in vitro.

PMID- 21950686
TI  - Topological partition of the elastic constants of crystals.
AB  - We present a partitioning of the elastic constants of a crystal into atomic
      contributions by using the atomic basin concept inherent to Bader's Quantum
      Theory of Atoms in Molecules. The partition is made by following the evolution of
      the cell volume and the atomic basin volumes under appropriately defined cell
      deformations. The method is carefully examined, including internal consistency
      checks. The transferability of atomic contributions between different crystals is
      determined by obtaining and comparing the oxygen contribution to the elastic
      constants of a selection of cubic oxides that includes the rock-salt, perovskite,
      antifluorite, and cuprite crystal families.

PMID- 21950688
TI  - Transfusion medicine history illustrated. Giving blood with music.

PMID- 21950687
TI  - High potency inhibition of hERG potassium channels by the sodium-calcium exchange
      inhibitor KB-R7943.
AB  - BACKGROUND AND PURPOSE: KB-R7943 is an isothiourea derivative that is used widely
      as a pharmacological inhibitor of sodium-calcium exchange (NCX) in experiments on
      cardiac and other tissue types. This study investigated KB-R7943 inhibition of
      hERG (human ether-a-go-go-related gene) K(+) channels that underpin the cardiac
      rapid delayed rectifier potassium current, I(Kr) . EXPERIMENTAL APPROACH: Whole
      cell patch-clamp measurements were made of hERG current (I(hERG) ) carried by
      wild-type or mutant hERG channels and of native rabbit ventricular I(Kr) .
      Docking simulations utilized a hERG homology model built on a MthK-based
      template. KEY RESULTS: KB-R7943 inhibited both I(hERG) and native I(Kr) rapidly
      on membrane depolarization with IC(50) values of ~89 and ~120 nM, respectively,
      for current tails at -40 mV following depolarizing voltage commands to +20 mV.
      Marked I(hERG) inhibition also occurred under ventricular action potential
      voltage clamp. I(hERG) inhibition by KB-R7943 exhibited both time- and voltage
      dependence but showed no preference for inactivated over activated channels.
      Results of alanine mutagenesis and docking simulations indicate that KB-R7943 can
      bind to a pocket formed of the side chains of aromatic residues Y652 and F656,
      with the compound's nitrobenzyl group orientated towards the cytoplasmic side of
      the channel pore. The structurally related NCX inhibitor SN-6 also inhibited
      I(hERG) , but with a markedly reduced potency. CONCLUSIONS AND IMPLICATIONS: KB
      R7943 inhibits I(hERG) /I(Kr) with a potency that exceeds that reported
      previously for acute cardiac NCX inhibition. Our results also support the
      feasibility of benzyloxyphenyl-containing NCX inhibitors with reduced potential,
      in comparison with KB-R7943, to inhibit hERG.

PMID- 21950689
TI  - Early hospital care of severe traumatic brain injury.
AB  - Head injury is one of the major causes of trauma-related morbidity and mortality
      in all age groups in the United Kingdom, and anaesthetists encounter this problem
      in many areas of their work. Despite a better understanding of the
      pathophysiological processes following traumatic brain injury and a wealth of
      research, there is currently no specific treatment. Outcome remains dependant on
      basic clinical care: management of the patient's airway with particular attention
      to preventing hypoxia; avoidance of the extremes of lung ventilation; and the
      maintenance of adequate cerebral perfusion, in an attempt to avoid exacerbating
      any secondary injury. Hypertonic fluids show promise in the management of
      patients with raised intracranial pressure. Computed tomography scanning has had
      a major impact on the early identification of lesions amenable to surgery, and
      recent guidelines have rationalised its use in those with less severe injuries.
      Within critical care, the importance of controlling blood glucose is becoming
      clearer, along with the potential beneficial effects of hyperoxia. The major
      improvement in outcome reflects the use of protocols to guide resuscitation,
      investigation and treatment and the role of specialist neurosciences centres in
      caring for these patients. Finally, certain groups are now recognised as being at
      greater risk, in particular the elderly, anticoagulated patient.

PMID- 21950690
TI  - Knowledge and skills of cancer clinical trials nurses in Australia.
AB  - AIMS:   This paper is a report of the development and testing of a questionnaire
      measuring knowledge and skills of cancer clinical trials nurse in Australia.
      BACKGROUND:   The role of cancer clinical trials nurse, widely acknowledged as an
      integral member of the clinical research team, has evolved in recent years.
      Elements of the clinical trials nurse role in cancer have previously been
      described. To evaluate specific cancer clinical trials nurse educational and
      training needs, the development of a valid and reliable tool is required.
      METHODS:   In 2009, a study was conducted in three stages. Stage I: questionnaire
      development and pilot testing; stage II: focus group; stage III: national survey.
      Internal consistency reliability testing and multi-trait analysis of item
      convergent/divergent validity were employed. Regression analysis was used to
      identify predictors of clinical trials nurse knowledge and skills. RESULTS:   The
      national survey was a 48-item questionnaire, measuring six clinical trial
      knowledge and seven skills sub-scales. Of 61 respondents, 90% were women, with
      mean age 43 years, 19 years as a Registered Nurse and 5 years as a cancer
      clinical trials nurse. Self-reported knowledge and skills were satisfactory to
      good. Internal consistency reliability was high (Cronbach's alpha: knowledge =
      0.98; skills = 0.90). Criteria for item convergent/divergent validity were met.
      Number of years as cancer clinical trials nurse was positively related to self
      reported knowledge and skills. CONCLUSION:   Preliminary data suggest that the
      national survey is reliable and valid. Data have contributed to better
      understanding the knowledge and skills of cancer clinical trials nurse in
      Australia and development of a postgraduate course in clinical trials.

PMID- 21950691
TI  - Multiple endocrine neoplasia type 1 in Japan: establishment and analysis of a
      multicentre database.
AB  - OBJECTIVE: Multiple endocrine neoplasia type 1 (MEN1) is less well recognized in
      Asian countries, including Japan, than in the West. The clinical features and
      optimal management of MEN1 have yet to be clarified in Japan. The aim of this
      study was to clarify the clinical features of Japanese patients with MEN1.
      DESIGN/PATIENTS: We established a MEN study group designated the 'MEN Consortium
      of Japan' in 2008, and asked physicians and surgeons to provide clinical and
      genetic information on patients they had treated. Of 680 registered patients, 560
      were analysed. MEASUREMENTS: Clinical and genetic features of Japanese patients
      with MEN1 were examined. RESULTS: Primary hyperparathyroidism,
      gastroenteropancreatic neuroendocrine tumours (GEPNET), and pituitary tumours
      were seen in 94.4%, 58.6% and 49.6% of patients, respectively. The prevalence of
      insulinoma was higher in the Japanese than in the West (22%vs 10%). In addition,
      37% of patients with thymic carcinoids were women, while most were men in western
      countries. The MEN1 mutation positive rate was 91.7% in familial cases and only
      49.3% in sporadic cases. Eight novel mutations were identified. Despite the
      availability of genetic testing for MEN1, the application of genetic testing,
      especially presymptomatic diagnosis for at-risk family members appeared to be
      insufficient. CONCLUSIONS: We established the first extensive database for Asian
      patients with MEN1. Although the clinical features of Japanese patients were
      similar to those in western countries, there were several characteristic
      differences between them.

PMID- 21950692
TI  - Bendamustine, Thalidomide and Dexamethasone is an effective salvage regimen for
      advanced stage multiple myeloma.

PMID- 21950693
TI  - Efficacy of acupuncture and identification of tear protein expression changes
      using iTRAQ quantitative proteomics in rabbits.
AB  - PURPOSE: To evaluate the effect of acupuncture on rabbit tear secretion and
      compare the difference in tear protein expression caused by acupuncture.
      MATERIALS AND METHODS: Ten male New Zealand White rabbits were enrolled in this
      study. The following acupoints around the left eye, Extra 1 (Taiyang), BL 2
      (Zanzhu) and SJ 23 (Sizhukong), were selected for acupuncture therapy. Each
      rabbit received 10 acupuncture sessions of 30 min, three times per week. A
      quantity of 50 MUl rabbit tear was collected at the pre- and post-acupuncture
      stage in every subject, respectively. Total protein content analysis, one
      dimensional gel electrophoresis and quantitative proteomics analysis (iTRAQ) were
      performed and the results were compared. RESULTS: Generally, the tear protein
      expression after acupuncture was different from that before acupuncture though to
      some extent they were similar. The time spent collecting rabbit tear after
      acupuncture was shorter than that before acupuncture. The total protein content
      in rabbit tear pre- and post-acupuncture was 7.12 MUg/MUl versus 11.28 MUg/MUl,
      respectively. One-dimensional gel electrophoresis showed that tear proteins
      collected before acupuncture were substantially different than post-acupuncture
      proteins. In total, twenty-eight tear proteins were identified by iTRAQ.
      Associated with acupuncture were six up-regulated proteins (tear lipocalin, alpha
      1-antiproteinase, histidine-rich glycoprotein, hemopexin, Vitamin D-binding
      protein, alpha-2-HS-glycoprotein) and five down-regulated proteins (Annexin A1,
      serum amyloid A-3 protein, Helicase-like transcription factor, 15 kDa protein A,
      protein S100-A9). CONCLUSIONS: The rabbit tear protein expression difference
      caused by acupuncture indicates that acupuncture not only stimulates lacrimal
      gland secretion function but also induces the quantitative change of some
      proteins in rabbit tear, which may support a positive effect of acupuncture in
      the treatment of dry eye.

PMID- 21950694
TI  - Long-term changes in corneal morphology induced by overnight orthokeratology.
AB  - PURPOSE: To assess long-term morphological and biometric corneal changes produced
      by overnight orthokeratology and to examine their recovery after cessation of
      contact lens wear. METHODS: Prospective, single-center, longitudinal trial.
      Fifteen right eyes with low to moderate myopia underwent overnight
      orthokeratology for 1 year. The central cornea was examined using a confocal
      microscope and changes determined in visual acuity, refractive error and corneal
      topography. Cell counts were performed using both the confocal microscope's
      software and the image analysis software of the USA Health Institute. All
      measurements were made during orthokeratology treatment and 1 month after
      discontinuing treatment. RESULTS: No significant changes in endothelial cell
      density were observed over time but polymegethism increased significantly and
      baseline values were not recovered (p < 0.01). Stromal cell density remained
      unchanged though numbers of activated keratocytes increased during the study and
      returned to baseline when lens wear ceased. Basal epithelium cell densities
      significantly fell (p < 0.01) and epithelial wing and superficial cells showed
      enhanced visibility (p < 0.05). Superficial cells increased in height and width;
      this width increase being significant after 1 year of orthokeratology (p < 0.01).
      All epithelial cell changes returned to baseline. Corneal thickness, Bowman layer
      thickness, subbasal plexus thickness and epithelial thickness were reduced in the
      central cornea but the stroma was thickened. Of these changes, the decrease in
      epithelium thickness reached statistical significance (p < 0.01) and baseline
      values were not recovered. CONCLUSION: Overnight orthokeratology induces
      structural and optical changes particularly in the central corneal epithelium
      during myopia treatment. If confirmed, the irreversible changes detected indicate
      a need for further investigation.

PMID- 21950695
TI  - Factors influencing the changes in coma-like aberrations after myopic laser in
      situ keratomileusis.
AB  - PURPOSE: To assess factors affecting changes in coma-like aberrations after
      myopic laser in situ keratomileusis (LASIK). METHODS: We retrospectively examined
      91 eyes of 48 patients undergoing LASIK (mean patient age +/- standard deviation,
      29.6 +/- 8.1 years; gender, 29 male and 19 female; manifest refraction, -4.76 +/-
      1.42 diopters). We quantitatively assessed the values of coma-like aberrations
      for 4-mm and 6-mm pupils using a Hartmann-Shack aberrometer before and 3 months
      after surgery. Multiple regression analysis was used to assess the relevant
      factors of the changes in coma-like aberrations. RESULTS: The mean changes in
      coma-like aberrations for 4-mm and 6-mm pupils were 0.08 +/- 0.09 MUm and 0.31 +/
      0.30 MUm, respectively. Explanatory variables relevant to the changes in coma
      like aberrations were, in order of influence, amount of spherical equivalent
      correction (partial regression coefficient B = 0.022, p <0.001 for a 4-mm pupil,
      B = 0.090, p <0.001 for a 6-mm pupil), and surgical technique (B = -0.062, p =
      0.01 for a 4-mm pupil, B = -0.169, p = 0.03 for a 6-mm pupil). No significant
      correlation was seen with other clinical factors such as age, gender, astigmatism
      correction, mean keratometric readings, central corneal thickness, or eye
      tracking (with or without). CONCLUSIONS: High myopic eyes requiring larger
      amounts of laser correction and eyes undergoing conventional LASIK tend to induce
      more coma-like aberration after surgery. Wavefront-guided LASIK may be a better
      surgical approach for preventing the induction of coma-like aberrations,
      especially in eyes with high myopia.

PMID- 21950696
TI  - Effect of cysteamine on oxidative stress-induced cell death of human corneal
      endothelial cells.
AB  - PURPOSE: The principal objective of this study was to evaluate the protective
      effect of cysteamine against the oxidative stress-induced cell death of human
      corneal endothelial cells. METHODS: In this study, human corneal endothelial
      cells (HCECs) were cultured according to a previously published method. With
      treatment of 0 mM or 5 mM of tert-butyl hydroperoxide (tBHP) with various
      concentrations (0-50 mM) of cysteamine, reactive oxygen species (ROS) production
      was measured using an oxidation-sensitive fluorescent probe, and
      dichlorofluorescein diacetate (DCFH-DA) methods. Cell viability was assayed via
      the Cell Counting Kit-8 method. The levels of cellular glutathione were also
      assessed enzymatically with glutathione reductase using a commercial glutathione
      assay kit (Cayman Chemical, USA). RESULTS: This study showed that cysteamine
      reduced 2',7'-dihydrodichlorofluorescein oxidation and increased glutathione.
      Cysteamine significantly inhibited tBHP-induced ROS production. Cysteamine
      treated cells evidenced higher viability relative to the controls at 5 mM tBHP,
      and cysteamine also effectively protected HCECs against ROS-induced cell death
      via an increase in intracellular glutathione. CONCLUSIONS: Our data indicate that
      cysteamine was not toxic at low concentrations and, at high concentrations,
      protects HCECs against oxidative injury-mediated cell death via the inhibition of
      ROS production, although cysteamine is toxic in cells at high concentrations
      without oxidative stress.

PMID- 21950697
TI  - Effect of hydroxypropyl-beta-cyclodextrin on the ocular bioavailability of
      dexamethasone from a pH-induced mucoadhesive hydrogel.
AB  - PURPOSE: Dexamethasone (DXN) is an effective anti-inflammatory drug in the
      treatment of acute and chronic eye disease such as uveitis. It is relatively
      lipophilic and permeates biological membranes quite easily. However, its low
      aqueous solubility limits its clinical usefulness. To circumvent this problem
      Hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was used as solubilizer and
      penetration enhancer for DXN. The purpose of this study was to develop HP-beta-CD
      based pH-induced mucoadhesive hydrogel for ophthalmic delivery of DXN to treat
      uveitis. MATERIALS AND METHODS: The formation of inclusion complex of DXN with HP
      beta-CD was characterized in solution and solid states by phase solubility, X-ray
      diffractometry and IR spectrum analyses. To improve ocular retention and
      sustained action Carbopol 980 NF and sodium carboxymethylcellulose (NaCMC) were
      added to the formulations as phase transition and mucoadhesive agents,
      respectively. RESULTS: The HP-beta-CD-based hydrogel system enhanced the
      solubility of DXN and the apparent stability constant (k') of the DXN-HP-beta-CD
      inclusion complex was found to be 258.62 M(-1). The optimum concentrations of
      Carbopol 980NF and NaCMC for the mucoadhesive hydrogel were 0.2% (w/v) and 0.4%
      (w/v), respectively. This mucoadhesive hydrogel could flow freely under non
      physiological condition and showed the character of pseudoplastic fluid under
      both physiological and non-physiological conditions. In vitro release of DXN from
      the HP-beta-CD complex in simulated tear fluid (STF, pH- 7.4), was influenced
      significantly by the properties and concentration of Carbopol and NaCMC. In vivo
      studies in rabbit eye showed a marked improvement in anti-inflammatory activity
      of mucoadhesive hydrogel-treated eye compared with a marketed solution
      formulation in a uveitis-induced rabbit eye model. CONCLUSION: The developed HP
      beta-CD-based mucoadhesive system is a viable alternative to conventional eye
      drops of DXN due to its ability to enhance bioavailability through its longer
      precorneal residence time and ability to sustain the release of the drug.

PMID- 21950698
TI  - Involvement of calpain 2 in ionomycin-induced cell death in cultured mouse lens
      epithelial cells.
AB  - PURPOSE: Calpains are calcium-activated, intracellular, non-lysosomal, cysteine
      proteases that hydrolyze lens crystallins and cytoskeletal proteins. Elevated
      calcium is a frequent finding in both rodent and human cataracts, and calpain 2
      is present in lenses of both species. Lens epithelium forms a critical barrier to
      influx of calcium, but the role of calpain 2 in lens epithelium is poorly
      characterized. Thus, the purpose of the present experiment was to determine the
      role of calpain 2 in lens epithelial cell death. METHODS: Mouse lens epithelial
      cells (alpha-TN4) were cultured with the calcium ionophore ionomycin to promote
      calcium influx. Release of LDH into the culture medium was measured as a general
      marker of cell death, while necrosis and apoptosis were detected by staining with
      ethidium homodimer III (EtD-III) or FITC-annexin V. Calpain activity was
      determined by zymography and immunoblotting for activation-associated, fragments
      of calpain. Breakdown products of calpain substrate alpha-spectrin were also
      detected by immunoblotting as additional markers of calpain activation. RESULTS:
      Calpain 2 was found to be the major calpain isozyme in alpha-TN4 cells. Ionomycin
      caused leakage of LDH into the medium, activation of calpain 2, proteolysis of
      alpha-spectrin, and changes in alpha-TN4 cell morphology and staining
      characteristic of necrotic cell death. Calpain inhibitor SNJ-1945 significantly
      inhibited these changes. CONCLUSIONS: The ability of mouse lens epithelium to
      maintain lens transparency would be compromised by activation of calpain 2 and
      associated necrotic cell death. Since calpain 2 is ubiquitously present in all
      animal lenses so far observed, the current results may predict the pathological
      consequences of calpain 2 activation in animal lenses including those of man.

PMID- 21950699
TI  - Influence of blue light-filtering intraocular lenses on retinal nerve fiber layer
      measurements by spectral-domain optical coherence tomography.
AB  - PURPOSE: The purpose of this study was to assess the influence of blue light
      filtering intraocular lenses (IOL) on peripapillary retinal nerve fiber layer
      (RNFL) thickness measurements by spectral-domain (SD) optical coherence
      tomography (OCT). METHODS: This prospective study included 50 eyes of 50
      patients. Patients were randomly assigned to receive either a blue light
      filtering IOL (acrysof IQ (SN60WF) [Alcon]) or a clear IOL (Tecnis (Z9003)
      [AMO]). The peripapillary RNFL thickness was measured using a Cirrus SD OCT
      before and 8 weeks after cataract surgery. Perioperative differences in RNFL
      thickness measurements and signal strengths (SS) were evaluated and compared in
      both IOL groups. RESULTS: Thirty-nine eyes of 39 patients were included in the
      final analysis. There was a significant increase in average RNFL thickness and SS
      after cataract surgery in both IOL groups. No significant difference in
      perioperative changes of RNFL measurements was noted between yellow and clear IOL
      groups. In the multivariable analysis, the factor affecting perioperative
      differences of RNFL measurements was not IOL type but SS. CONCLUSIONS: Our data
      suggests that blue-light filtering IOL does not influence RNFL thickness
      measurements by Cirrus SD-OCT.

PMID- 21950700
TI  - Evaluation of in vivo human retinal morphology and function in myopes.
AB  - PURPOSE: To compare the retinal sensitivity, using Microperimeter and the
      morphological changes in retinal layers, using Spectral Domain Optical Coherence
      Tomography (SD-OCT), between myopes and age-matched emmetropes. METHODS: Twenty
      nine myopic eyes and 29 emmetropic eyes were enrolled in this prospective case
      control study. All subjects underwent subjective refraction as part of the
      ophthalmic examination and in addition, SDOCT and Microperimetry were performed.
      Based on the reflectivity on the OCT cross sections, the thickness of the retinal
      layers was measured 2.5 mm on either side of the fovea. RESULTS: The mean retinal
      sensitivity was significantly (p = 0.001) reduced in myopes (17.31 +/- 1.80 dB;
      mean +/- SD) compared to that of emmetropes (18.61 +/- 1.08 dB). SD-OCT did not
      show any significant difference in the photoreceptor layer and foveal thickness
      between myopes and emmetropes. The retinal pigment epithelium thickness was
      significantly reduced in myopes (35.03 +/- 4.21 um) compared to emmetropes (37.74
      +/- 4.30 um) (p = 0.019). We found a significant positive correlation between
      refractive error and mean retinal sensitivity (r = 0.725, p = <0.001).
      CONCLUSION: The retinal sensitivity was significantly reduced in myopes in spite
      of normal retinal morphology indicating that functional changes may precede
      structural changes.

PMID- 21950701
TI  - Single cell imaging of the chick retina with adaptive optics.
AB  - PURPOSE: The chick eye is extensively used as a model in the study of myopia and
      its progression; however, analysis of the photoreceptor mosaic has required the
      use of excised retina due to the uncorrected optical aberrations in the lens and
      cornea. This study implemented high resolution adaptive optics (AO) retinal
      imaging to visualize the chick cone mosaic in vivo. METHODS: The New England
      College of Optometry (NECO) AO fundus camera was modified to allow high
      resolution in vivo imaging on two 6-week-old White Leghorn chicks (Gallus gallus
      domesticus)-labeled chick A and chick B. Multiple, adjacent images, each with a
      2.5(o) field of view, were taken and subsequently montaged together. This process
      was repeated at varying retinal locations measured from the tip of the pecten.
      Automated software was used to determine the cone spacing and density at each
      location. Voronoi analysis was applied to determine the packing arrangement of
      the cones. RESULTS: In both chicks, cone photoreceptors were clearly visible at
      all retinal locations imaged. Cone densities measured at 36(o) nasal-12(o)
      superior retina from the pecten tip for chick A and 40(o) nasal-12(o) superior
      retina for chick B were 21,714 +/- 543 and 26,105 +/- 653 cones/mm(2)
      respectively. For chick B, a further 11 locations immediately surrounding the
      pecten were imaged, with cone densities ranging from 20,980 +/- 524 to 25,148 +/-
      629 cones/mm(2). CONCLUSION: In vivo analysis of the cone density and its packing
      characteristics are now possible in the chick eye through AO imaging, which has
      important implications for future studies of myopia and ocular disease research.

PMID- 21950702
TI  - Comparing treatment of neovascular age-related macular degeneration with
      sequential intravitreal Avastin and Macugen versus intravitreal mono-therapy--a
      pilot study.
AB  - PURPOSE: To examine if the sequential treatment of Avastin and Macugen is safe
      and more efficient than the mono-therapies in a prospective randomized masked
      pilot study. MATERIALS AND METHODS: Subjects with exudative age-related macular
      degeneration were randomized to receive three intravitreal injections of either 1
      mg of Avastin, 0.3 mg Macugen, or first 1 mg Avastin followed by retreatment of
      0.3 mg Macugen. Follow-up examinations were performed after 1, 6, 12 weeks, and 6
      months. RESULTS: Forty-eight subjects were included (13:18:17). Avastin resulted
      in lasting significant changes in visual acuity at 6 weeks, increase in contrast
      sensitivity at 6 weeks, and a significant decrease in macular thickness after 6
      and 12 weeks. Macugen showed a significant decrease in retinal thickness after 6
      weeks, but a significant decrease in visual acuity after 6 months, and a
      significant decrease in contrast sensitivity after 12 weeks and 6 months. The
      sequential treatment showed a decrease in retinal thickness after 1 and 12 weeks.
      CONCLUSION: Avastin alone is more effective in increasing visual acuity and
      contrast sensitivity and decreasing retinal thickness, than Macugen or the
      sequential treatment. We conclude that the sequential treatment of Avastin with
      Macugen is safe, but the single treatment of Avastin is more efficient.

PMID- 21950703
TI  - Effects of Y-39983, a selective Rho-associated protein kinase inhibitor, on blood
      flow in optic nerve head in rabbits and axonal regeneration of retinal ganglion
      cells in rats.
AB  - PURPOSE: To investigate the effects of Y-39983, a selective Rho-associated coiled
      coil-forming protein kinase inhibitor, on blood flow in the optic nerve head
      (ONH) in rabbits and axonal regeneration of retinal ganglion cells (RGCs) in
      rats. METHODS: Blood flow in ONH was measured by the laser speckle method after
      topical administration of 0.05% Y-39983 solution or its vehicle in rabbit eyes.
      To investigate the effects of Y-39983 on axonal regeneration of RGCs, RGCs
      purified from rat eyes were cultured with or without 10 MUM Y-39983 and
      morphologically observed by phase-contrast microscopy. Moreover, the effects of
      intravitreal administration of Y-39983 were evaluated using an in vivo model of
      axotomized RGCs in peripheral nerve-grafted rats. RESULTS: Topical administration
      of 0.05% Y-39983 solution significantly increased blood flow in ONH compared with
      the vehicle group in rabbits. Maximum increase in blood flow in the 0.05% Y-39983
      group was 122.84 +/- 5.98 % (Mean +/- S.E.) at 90 minutes after administration
      compared with before administration. Neurites in rat RGCs treated with 10 MUM Y
      39983 were extended compared with those without Y-39983 treatment of RGCs in
      vitro. Y-39983 dose-dependently increased the number of RGCs with regenerating
      axons in vivo. The numbers of RGCs with regenerating axons in 10 and 100 MUM Y
      39983-treated rats were 99.3 +/- 10.5 and 169.5 +/- 43.3 cells/mm(2) (Mean +/-
      S.D.), respectively, and significantly increased compared with those in saline
      treated rats (43.3 +/- 6.0 cells/mm(2)). CONCLUSION: Y-39983 may be a candidate
      drug not only for lowering of IOP but also for increasing of blood flow in ONH in
      the treatment of glaucoma. Moreover, Y-39983 may have therapeutic potential for
      axonal regeneration of RGCs in the treatment of diseases with degenerating axons
      of RGCs including glaucoma, although improvements of formulation or route of
      administration are needed in order to reach an effective concentration in retina.

PMID- 21950704
TI  - Severity of acute illness is associated with baseline readiness to change in
      medical intensive care unit patients with unhealthy alcohol use.
AB  - BACKGROUND: Unhealthy alcohol use predisposes to multiple conditions that
      frequently result in critical illness and is present in up to one-third of
      patients admitted to a medical intensive care unit (ICU). We sought to determine
      the baseline readiness to change in medical ICU patients with unhealthy alcohol
      use and hypothesized that the severity of acute illness would be independently
      associated with higher scores on readiness to change scales. We further sought to
      determine whether this effect is modified by the severity of unhealthy alcohol
      use. METHODS: We performed a cross-sectional observational study of current
      regular drinkers in 3 medical ICUs. The Alcohol Use Disorders Identification Test
      was used to differentiate low-risk and unhealthy alcohol use and further
      categorize patients into risky alcohol use or an alcohol use disorder. The
      severity of a patient's acute illness was assessed by calculating the Acute
      Physiologic and Chronic Health Evaluation II (APACHE II) score at the time of
      admission to the medical ICU. Readiness to change was assessed using standardized
      questionnaires. RESULTS: Of 101 medical ICU patients who were enrolled, 65 met
      the criteria for unhealthy alcohol use. The association between the severity of
      acute illness and readiness to change depended on the instrument used. A higher
      severity of illness measured by APACHE II score was an independent predictor of
      readiness to change as assessed by the Stages of Change Readiness and Treatment
      Eagerness Scale (Taking Action scale; p < 0.01). When a visual analog scale was
      used to assess readiness to change, there was a significant association with
      severity of acute illness (p < 0.01) that was modified by the severity of
      unhealthy alcohol use (p = 0.04 for interaction term). CONCLUSIONS: Medical ICU
      patients represent a population where brief interventions require further study.
      Studies of brief intervention should account for the severity of acute illness
      and the severity of unhealthy alcohol use as potential effect modifiers.

PMID- 21950705
TI  - Cutaneous leishmaniasis in a Japanese returnee from West Africa successfully
      treated with liposomal amphotericin B.
AB  - Leishmaniasis has been occasionally reported in returnees from endemic areas.
      Here, we report a case of cutaneous leishmaniasis in a 33-year-old Japanese man
      who presented with a skin nodule after returning from an 8-year stay in West
      Africa including Burkina Faso. He was successfully treated with liposomal
      amphotericin B with no significant adverse effects. This is the first Japanese
      case of cutaneous leishmaniasis treated successfully with liposomal amphotericin
      B.

PMID- 21950706
TI  - Arsenite oxidation by a poorly-crystalline manganese oxide. 3. Arsenic and
      manganese desorption.
AB  - Arsenic (As) mobility in the environment is greatly affected by its oxidation
      state and the degree to which it is sorbed on metal oxide surfaces. Manganese
      oxides (Mn oxides) have the ability to decrease overall As mobility both by
      oxidizing toxic arsenite (As(III)) to less toxic arsenate (As(V)), and by sorbing
      As. However, the effect of competing ions on the mobility of As sorbed on Mn
      oxide surfaces is not well understood. In this study, desorption of As(V) and
      As(III) from a poorly crystalline phyllomanganate (delta-MnO(2)) by two
      environmentally significant ions is investigated using a stirred-flow technique
      and X-ray absorption spectroscopy (XAS). As(III) is not observed in solution
      after desorption under any conditions used in this study, agreeing with previous
      studies showing As sorbed on Mn-oxides exists only as As(V). However, some As(V)
      is desorbed from the delta-MnO(2) surface under all conditions studied, while
      neither desorptive used in this study completely removes As(V) from the delta
      MnO(2) surface.

PMID- 21950707
TI  - Bacteremia in feverish children presenting to the emergency department: a
      retrospective study and literature review.
AB  - AIM: To evaluate the incidence of bacteremia, and the isolated pathogens, in well
      appearing children with fever without source (FWS) presenting to the pediatric
      emergency department (PED), after pneumococcal conjucate vaccine - 7 valent (PCV
      7) widespread introduction in the Veneto region of north-eastern Italy, and to
      review the main literature contributions on the subject. METHODS: Blood cultures
      performed at the PED of Padova from 1 June 2006 to 31 January 2009 in febrile
      children aged 1-36 months were retrospectively retrieved. Medical records of
      previously healthy well-appearing children with FWS were identified and reviewed.
      RESULTS: The study finally included 392 patients. Bacteremia rate was 0.34% (95%
      CI 0-1) in the age group 3-36 months and 2% (95% CI 0-4.7) in infants 1-3 months.
      No Streptococcus pneumoniae was isolated. The literature review identified 10
      relevant studies carried out in the USA and Spain showing an overall bacteremia
      rate <1% for feverish children aged 3-36 months, with values <0.5% in settings
      with high PCV-7 coverage. CONCLUSION: Overall bacteremia rate is currently <0.5%
      in well-appearing children aged 3-36 months with FWS attending the PED in areas
      with PCV-7 widespread vaccination and is sufficiently low to preclude laboratory
      testing in favour of close follow-up. Further research is needed to evaluate a
      more conservative approach in infants 2-3 months of age.

PMID- 21950720
TI  - Clinical evaluation of a simultaneous closed-loop anaesthesia control system for
      depth of anaesthesia and neuromuscular blockade*.
AB  - We developed a closed-loop system to control the depth of anaesthesia and
      neuromuscular blockade using the bispectral index and the electromyogram
      simultaneously and evaluated the clinical performance of this combined system for
      general anaesthesia. Twenty-two adult patients were included in this study.
      Anaesthesia was induced by a continuous infusion of remifentanil at 0.4 MUg.kg(
      1) .min(-1) (induction dose) and then 0.25 MUg.kg(-1) .min(-1) (maintenance dose)
      and propofol at 2 mg.kg(-1) 3 min later. The combined automatic control was
      started 2 min after tracheal intubation. The depth of anaesthesia was recorded
      using bispectral index monitoring using a target value of 40. The target value of
      neuromuscular blockade, using mivacurium, was a T1/T1(0) twitch height of 10%.
      The precision of the system was calculated using internationally defined
      performance parameters. Twenty patients were included in the data analysis. The
      mean (SD) duration of simultaneous control was 129 (69) min. No human
      intervention was necessary during the computer-controlled administration of
      propofol and mivacurium. All patients assessed the quality of anaesthesia as
      'good' to 'very good'; there were no episodes of awareness. The mean (SD) median
      performance error, median absolute performance error and wobble for the control
      of depth of anaesthesia and for neuromuscular blockade were -0.31 (1.78), 6.76
      (3.45), 6.32 (2.93) and -0.38 (1.68), 3.75 (4.83), 3.63 (4.69), respectively. The
      simultaneous closed-loop system using propofol and mivacurium was able to
      maintain the target values with a high level of precision in a clinical setting.

PMID- 21950721
TI  - Behavioral tests as indicator for pain and distress in a primate endometriosis
      model.
AB  - BACKGROUND: As common marmosets (Callithrix jacchus) are frequently used
      experimental animals, sensitive test systems are needed to evaluate impairment
      and pain caused by procedures and diseases. METHODS: A diurnal profile of healthy
      animals was obtained by videotaping. Differences in social behavior and cognitive
      skills between marmosets with established endometriosis and healthy monkeys were
      investigated using the videotaping, the Wisconsin General Test Apparatus (WGTA),
      and a food tree. RESULTS: The marmosets showed a mostly trimodal course of
      activity. Social grooming and activity were significantly decreased in animals
      with endometriosis; furthermore, the diseased monkeys habituated significantly
      worse to the cognitive test settings. The food tree experiments offered no
      differences between diseased and control animals. CONCLUSION: The videotaping and
      the WGTA are suitable methods to detect disease-related impairments in common
      marmosets, which is essential for the refinement of experiments.

PMID- 21950722
TI  - Transurethral bladder catheterization of male rhesus macaques: a refinement of
      approach.
AB  - BACKGROUND: Successful transurethral bladder catheterization in male non-human
      primates can be challenging. An optimized approach for consistent and
      reproducible catheterization using a refined technique is described. METHODS:
      Under sedated and non-sedated conditions, transurethral bladder catheterization
      was performed on 25 male rhesus macaques of varying ages and body weights over
      time. A refined technique ensuring optimal lubrication of the urethral canal
      prior to catheter insertion was utilized along with various single and multiple
      lumen catheters. RESULTS: All animals were successfully catheterized. Sixty-five
      catheterization sessions were conducted with a high overall success rate (100%).
      The incidence of catheter (10%) and post-catheterization (2%) complications was
      low. CONCLUSIONS: The urinary bladder of male rhesus can be reliably and
      reproducibly catheterized with minimal complication using this approach.
      Successful catheterization was facilitated by thorough urethral lubrication and
      using suitable catheters. In addition, this approach may be performed without
      sedation on thoroughly conditioned animals.

PMID- 21950724
TI  - Spinal muscular atrophy carrier frequency and estimated prevalence of the disease
      in Moroccan newborns.
AB  - Spinal muscular atrophy (SMA) is one of the most common autosomal recessive
      diseases caused by homozygous deletion of exon 7 of the survival motor neuron 1
      (SMN1) gene in approximately 95% of SMA patients. Carrier frequency studies of
      SMA have been reported for various populations. The aim of our study was to
      estimate the carrier frequency of the common SMN1 exon 7 deletion in the Moroccan
      population to achieve an insight into the prevalence of SMA in Morocco. In this
      study, we used a reliable quantitative real-time polymerase chain reaction assay
      with SYBR Green I dye to determine the copy number of the SMN1 gene. Analysis of
      150 Moroccan newborns predicts a carrier frequency of approximately 1:25, which
      would mean a calculated SMA prevalence of 1:1800 after correction due to
      consanguinity. These results show as expected that the SMA carrier frequency in
      Morocco is higher than in the European populations and is close to those of
      Middle Eastern countries. Genetic carrier testing for genetic counseling should
      be recommended particularly to families with a clear clinical history of SMA.

PMID- 21950725
TI  - Atypical nail dystrophy in a possible case of Nagashima-type palmoplantar
      keratosis.

PMID- 21950726
TI  - Pioglitazone induces regression and stabilization of coronary atherosclerotic
      plaques in patients with impaired glucose tolerance.
AB  - AIMS: To observe the effects of pioglitazone on coronary plaque area, plaque
      burden, serum high-sensitivity C-reactive protein, adiponectin and plasma
      endothelin-1 levels in patients with impaired glucose tolerance and coronary
      borderline lesions. METHODS: Thirty patients were randomly divided into two
      groups: a pioglitazone group and a control group. The latter was administered
      placebo in addition to standard therapy; the former pioglitazone 15 mg/d in
      addition to standard therapy. Before treatment and 6 months later, left
      ventricular ejection fraction, serum lipid profile, high-sensitivity C-reactive
      protein, adiponectin and plasma endothelin-1 levels were detected. Coronary
      plaque area and plaque burden were examined using intravascular ultrasound.
      RESULTS: No significant differences were found in left ventricular ejection
      fraction and serum lipid levels pre- and post-trial. Compared with the control
      group, 6 months' treatment with pioglitazone significantly decreased coronary
      plaque burden (50.7 +/- 11.1 vs. 64.1 +/- 10.3%, P < 0.05), plaque area (6.22 +/-
      2.03 vs. 8.31 +/- 4.29, P < 0.05), thin-cap fibroatheroma prevalence (11 vs. 22%,
      P < 0.05) and percentage of necrotic core area (16 +/- 8 vs. 31 +/- 7%, P <
      0.05). Compared with the control group, serum high-sensitivity C-reactive protein
      and plasma endothelin-1 levels were significantly lower and adiponectin level
      significantly higher in patients in the pioglitazone group. Serum adiponectin
      level was negatively correlated with plasma endothelin-1 level and coronary
      plaque area (r = 0.739 and -0.431, respectively, both P < 0.05). CONCLUSIONS:
      Pioglitazone may induce regression and stabilization of coronary atherosclerotic
      plaques. The mechanisms might involve inhibition of inflammation, increase in
      adiponectin level and improvement in endothelial function.

PMID- 21950727
TI  - A double-blind, placebo-controlled trial to assess the efficacy of quetiapine
      fumarate XR in very heavy-drinking alcohol-dependent patients.
AB  - BACKGROUND: Despite advances in developing medications to treat alcohol
      dependence, few such medications have been approved by the Food and Drug
      Administration. Identified molecular targets are encouraging and can lead to the
      development and testing of new compounds. Atypical antipsychotic medications have
      been explored with varying results. Prior research suggests that the
      antipsychotic quetiapine may be beneficial in an alcohol-dependent population of
      very heavy drinkers. METHODS: In this double-blind, placebo-controlled trial, 224
      alcohol-dependent patients who reported very heavy drinking were recruited across
      5 clinical sites. Patients received either quetiapine or placebo and Medical
      Management behavioral intervention. Patients were stratified on gender, clinical
      site, and reduction in drinking prior to randomization. RESULTS: No differences
      between the quetiapine and placebo groups were detected in the primary outcome,
      percentage heavy-drinking days, or other drinking outcomes. Quetiapine
      significantly reduced depressive symptoms and improved sleep but had no effect on
      other nondrinking outcomes. Results from a subgroup analysis suggest that
      patients who reduced their drinking prior to randomization had significantly
      better drinking outcomes during the maintenance phase (p < 0.0001). No
      significant interactions, however, were observed between reducer status and
      treatment group. Finally, quetiapine was generally well tolerated. Statistically
      significant adverse events that were more common with quetiapine versus placebo
      include dizziness (14 vs. 4%), dry mouth (32 vs. 9%), dyspepsia (13 vs. 2%),
      increased appetite (11 vs. 1%), sedation (15 vs. 3%), and somnolence (34 vs. 9%).
      CONCLUSIONS: This multisite clinical trial showed no efficacy for quetiapine
      compared with placebo at reducing alcohol consumption in heavy-drinking alcohol
      dependent patients.

PMID- 21950728
TI  - Preclinical evaluation of a novel SIRT1 modulator SRT1720 in multiple myeloma
      cells.
AB  - SIRT1 belongs to the silent information regulator 2 (Sir2) protein family of
      enzymes and functions as a NAD(+) -dependent class III histone deacetylase. Here,
      we examined the anti-multiple myeloma (MM) activity of a novel oral agent,
      SRT1720, which targets SIRT1. Treatment of MM cells with SRT1720 inhibited growth
      and induced apoptosis in MM cells resistant to conventional and bortezomib
      therapies without significantly affecting the viability of normal cells.
      Mechanistic studies showed that anti-MM activity of SRT1720 is associated with:
      (i) activation of caspase-8, caspase-9, caspase-3, poly(ADP) ribose polymerase;
      (ii) increase in reactive oxygen species; (iii) induction of phosphorylated
      ataxia telangiectasia mutated/checkpoint kinase 2 signalling; (iv) decrease in
      vascular endothelial growth factor-induced migration of MM cells and associated
      angiogenesis; and (v) inhibition of nuclear factor-kappaB. Blockade of ATM
      attenuated SRT1720-induced MM cell death. In animal tumour model studies, SRT1720
      inhibited MM tumour growth. Finally, SRT1720 enhanced the cytotoxic activity of
      bortezomib or dexamethasone. Our preclinical studies provide the rationale for
      novel therapeutics targeting SIRT1 in MM.

PMID- 21950729
TI  - Interactive priming of biochar and labile organic matter mineralization in a
      smectite-rich soil.
AB  - Biochar is considered as an attractive tool for long-term carbon (C) storage in
      soil. However, there is limited knowledge about the effect of labile organic
      matter (LOM) on biochar-C mineralization in soil or the vice versa. An incubation
      experiment (20  degrees C) was conducted for 120 days to quantify the interactive
      priming effects of biochar-C and LOM-C mineralization in a smectitic clayey soil.
      Sugar cane residue (source of LOM) at a rate of 0, 1, 2, and 4% (w/w) in
      combination with two wood biochars (450 and 550  degrees C) at a rate of 2% (w/w)
      were applied to the soil. The use of biochars (~ -360/00) and LOM (-12.70/00) or
      soil (-14.30/00) with isotopically distinct delta(13)C values allowed the
      quantification of C mineralized from biochar and LOM/soil. A small fraction (0.4
      1.1%) of the applied biochar-C was mineralized, and the mineralization of biochar
      C increased significantly with increasing application rates of LOM, especially
      during the early stages of incubation. Concurrently, biochar application reduced
      the mineralization of LOM-C, and the magnitude of this effect increased with
      increasing rate of LOM addition. Over time, the interactive priming of biochar-C
      and LOM-C mineralization was stabilized. Biochar application possesses a
      considerable merit for long-term soil C-sequestration, and it has a stabilizing
      effect on LOM in soil.

PMID- 21950730
TI  - Case of angiolymphoid hyperplasia with eosinophilia associated with scabies
      infestation.

PMID- 21950731
TI  - Growth hormone regimens in Australia: analysis of the first 3 years of treatment
      for idiopathic growth hormone deficiency and idiopathic short stature.
AB  - OBJECTIVE: To investigate response to growth hormone (GH) in the first, second
      and third years of treatment for all idiopathic GH-deficient (GHD) and idiopathic
      short stature (ISS) patients in Australia. CONTEXT: Eligibility for subsidized GH
      treatment in Australia is determined on auxological criteria for the indication
      of Short Stature and Slow Growth (SSSG), which includes ISS (SSSG-ISS). The
      biochemical GHD (BGHD, peak GH < 10 mU/l) and SSSG indications are treated
      similarly: starting dose of 4.5 mg/m(2)/week with provision for incremental
      dosing. Some ISS patients were specifically diagnosed with familial short stature
      (SSSG-FSS). DESIGN: Responses for each year of treatment for BGHD, SSSG-ISS and
      SSSG-FSS cohorts were compared in relation to influencing variables and with
      international benchmarks. The effect of incremental dosing was assessed.
      PATIENTS: Australian BGHD, SSSG-ISS and SSSG-FSS patients who had completed 1, 2,
      or 3 years of treatment and were currently receiving GH. MEASUREMENTS: Growth
      hormone dose, change in height-standard deviation score (DeltaSDS) and growth
      velocity (GV). RESULTS: First-year response was 2-3 times greater than that in
      subsequent years: DeltaSDS(1st year) = 0.92, 0.50 and 0.46 for BGHD, SSSG-ISS and
      SSSG-FSS, respectively. Responses were similar to international reports and
      inversely related to age at commencement of GH. First-year GV-for-age for BGHD
      patients was similar to international standards for idiopathic GHD. However,
      girls had an inferior response to boys when treatment commenced at <6 years of
      age. First-year GV-for-age for SSSG-ISS/FSS patients was less than ISS standards.
      Dose increments attenuated the first- to second-year decline in response to BGHD
      but marginally improved the responses for SSSG-ISS/FSS. CONCLUSIONS: The
      Australian auxology-based GH programme produces comparable responses to
      international programmes. A lower starting dose is offset by the initiation of
      treatment at younger ages. Incremental dosing does not appear optimal. A first
      year dose of 6.4-6.9 mg/m(2)/week for GHD and 8.9 mg/m(2)/week for ISS with early
      commencement of GH treatment may be most efficacious.

PMID- 21950732
TI  - Self-assembled carbohydrate hydrogels for prolonged pain management.
AB  - CONTEXT: Nanoparticulate systems are new tools that promise a revolution in the
      field of drug delivery. Among their numerous benefits, polyelectrolyte complexes
      (PECs) have shown to provide a barrier to drug release. OBJECTIVE: In this study,
      PECs, in the form of self-assembled polymeric nanogels, have been studied as
      potential drug carriers of the freely soluble drug tramadol HCL trying to achieve
      a prolonged percutaneous permeation. METHODOLOGY: The hydrogels were subjected to
      swelling, rheology, release and permeation studies and were characterized by FTIR
      spectroscopy and scanning electron microscopy. RESULTS: P2 hydrogel composed of
      chitosan-carrageenan (1-1) PEC attained the most compromised rheological shear
      thinning thixotropic behavior, good bioadhesive properties, the most retarded
      release and permeation with an f2 value <50 compared to chitosan hydrogel,
      altogether with non-irritancy to the skin. SEM photographs showed that P2 has
      spherical nanosized particles structure. CONCLUSION: This approach can provide us
      promising results for an around-the-clock analgesia with better safety and
      tolerability profile.

PMID- 21950733
TI  - A family systems nursing intervention model for paediatric health crisis.
AB  - AIM: This article discusses the development of a family systems nursing
      intervention for clinical use in health crisis. BACKGROUND: Although studies in
      paediatric critical care provide evidence that family stress is an important
      clinical phenomenon, studies have demonstrated that few nurses have the requisite
      family intervention skills to provide family members with adequate support during
      crisis. In addition, few intervention studies that focus on provider-family
      relationships with the goal of reducing stress have been reported. This article
      contributes to the literature by redressing this lack. Data sources.  The
      literature search supporting this project spanned from 1980 to 2009 and included
      searches from classic nursing theory, family theory and relevant nursing research
      specific to the design of the intervention reported. DISCUSSION: The goal of the
      intervention is to provide a theoretical and practical foundation for explicit
      action that enhances relationships with caregivers thereby supporting the
      integrity of the family and enhancing their coping abilities. The intervention,
      based on the Family Systems Model and the family's understandings of the
      situation, defines specific goals and desired outcomes to guide strategic
      actions. Discussion of the conceptual foundation, procedural development and an
      example of the protocol is provided. Implications for nursing.  The intervention
      is designed for nurses with limited knowledge in family theory to aid them to
      better help families dealing with stress. CONCLUSION: The proposed intervention
      can be used to increase nurses' skills in family centred nursing care. Although
      designed for use in paediatric critical care, it can, with modifications, be used
      in other nursing specialty areas.

PMID- 21950735
TI  - Pioglitazone is a valid alternative to rosiglitazone.
AB  - In 2000, two new thiazolidinediones, pioglitazone and rosiglitazone, were
      approved for the treatment of type 2 diabetes mellitus (T2DM). Administered as
      monotherapy or in combination with other antihyperglycemic agents, they
      represented an effective option for achieving or maintaining good glycemic
      control in patients with T2DM. Despite their efficacy, there was increasing
      concern regarding the potential of an increased cardiovascular risk with
      rosiglitazone. This resulted in the suspension of rosiglitazone from the European
      market by the European Medicines Agency in September 2010. This article focuses
      on the various steps that led to this important decision, and discusses a
      possible alternative for the treatment of patients receiving rosiglitazone.

PMID- 21950734
TI  - CONSTANS and ASYMMETRIC LEAVES 1 complex is involved in the induction of
      FLOWERING LOCUS T in photoperiodic flowering in Arabidopsis.
AB  - Plants monitor changes in day length to coordinate flowering with favorable
      seasons to increase their fitness. The day-length specific induction of FLOWERING
      LOCUS T (FT) regulated by CONSTANS (CO) is the crucial aspect of photoperiodic
      flowering in Arabidopsis thaliana. Recent studies have elucidated some mechanisms
      of CO-dependent FT induction. Here, we demonstrate another mechanism of CO
      dependent FT regulation. Our results indicate that CO protein partially regulates
      FT transcription by forming a complex with ASYMMETRIC LEAVES 1 (AS1) protein,
      which regulates leaf development partly by controlling gibberellin (GA) levels.
      We identified AS1 as a CO-interacting protein in yeast and verified their
      interaction in vitro and in planta. We also showed that the temporal and spatial
      expression pattern of AS1 overlapped with that of CO. In addition, as1 mutants
      showed GA-independent delayed flowering under different light/dark conditions. FT
      expression levels in the as1 mutants and the SUC2:CO-HA/as1 line under long-day
      and 12-h light/12-h dark conditions were reduced compared with wild-type plants
      and the SUC2:HA-CO line, respectively. Moreover, AS1 bound directly to the
      specific regions of the FT promoter in vivo. These results indicate that CO forms
      a functional complex with AS1 to regulate FT expression and that AS1 plays
      different roles in two regulatory pathways, both of which concomitantly regulate
      the precise timing of flowering.

PMID- 21950736
TI  - Polymorphisms of ADORA2A modulate psychomotor vigilance and the effects of
      caffeine on neurobehavioural performance and sleep EEG after sleep deprivation.
AB  - BACKGROUND AND PURPOSE: Prolonged wakefulness impairs sustained vigilant
      attention, measured with the psychomotor vigilance task (PVT), and induces a
      compensatory increase in sleep intensity in recovery sleep, quantified by slow
      wave activity (SWA) in the sleep electroencephalogram (EEG). These effects of
      sleep deprivation are counteracted by the adenosine receptor antagonist caffeine,
      implying involvement of the adenosine neuromodulator/receptor system. To examine
      a role for adenosine A(2A) receptors, we investigated whether variation of the
      A(2A) receptor gene (ADORA2A) modified effects of caffeine on PVT and SWA after
      sleep deprivation. EXPERIMENTAL APPROACH: A haplotype analysis of eight single
      nucleotide polymorphisms of ADORA2A was performed in 82 volunteers. In 45 young
      men carrying five different allele combinations, we investigated the effects of
      prolonged waking and 2 * 200 mg caffeine or 2 * 100 mg modafinil on psychomotor
      vigilance, sleepiness, and the waking and sleep EEG. KEY RESULTS: Throughout
      extended wakefulness, the carriers of haplotype HT4 performed faster on the PVT
      than carriers of non-HT4 haplotype alleles. In haplotype HT4, caffeine failed to
      counteract the waking-induced impairment of PVT performance and the rebound of
      SWA in recovery sleep. However, caffeine was effective in non-HT4 allele
      carriers, and modafinil reduced the consequences of prolonged waking,
      independently of ADORA2A haplotype. CONCLUSIONS AND IMPLICATIONS: Common genetic
      variation of ADORA2A is an important determinant of psychomotor vigilance in
      rested and sleep-deprived state. It also modulates individual responses to
      caffeine after sleep deprivation. These findings demonstrate a role for adenosine
      A(2A) receptors in the effects of prolonged wakefulness on vigilant attention and
      the sleep EEG.

PMID- 21950737
TI  - In vitro and in vivo neuroprotective activity of the cardiac glycoside oleandrin
      from Nerium oleander in brain slice-based stroke models.
AB  - The principal active constituent of the botanical drug candidate PBI-05204, a
      supercritical CO(2) extract of Nerium oleander, is the cardiac glycoside
      oleandrin. PBI-05204 shows potent anticancer activity and is currently in phase I
      clinical trial as a treatment for patients with solid tumors. We have previously
      shown that neriifolin, which is structurally related to oleandrin, provides
      robust neuroprotection in brain slice and whole animal models of ischemic injury.
      However, neriifolin itself is not a suitable drug development candidate and the
      FDA-approved cardiac glycoside digoxin does not cross the blood-brain barrier. We
      report here that both oleandrin as well as the full PBI-05204 extract can also
      provide significant neuroprotection to neural tissues damaged by oxygen and
      glucose deprivation as occurs in ischemic stroke. Critically, we show that the
      neuroprotective activity of PBI-05204 is maintained for several hours of delay of
      administration after oxygen and glucose deprivation treatment. We provide
      evidence that the neuroprotective activity of PBI-05204 is mediated through
      oleandrin and/or other cardiac glycoside constituents, but that additional, non
      cardiac glycoside components of PBI-05204 may also contribute to the observed
      neuroprotective activity. Finally, we show directly that both oleandrin and the
      protective activity of PBI-05204 are blood brain barrier penetrant in a novel
      model for in vivo neuroprotection. Together, these findings suggest clinical
      potential for PBI-05204 in the treatment of ischemic stroke and prevention of
      associated neuronal death.

PMID- 21950738
TI  - Functional characterization of pfm in protein secretion and lung infection of 
      Pseudomonas aeruginosa.
AB  - Lung infections caused by Pseudomonas aeruginosa in cystic fibrosis (CF) patients
      cause progressive airway obstruction and tissue damage, which is the predominant
      cause of morbidity and mortality in patients with CF. This paper describes the
      functional characterization of the pfm gene (open reading frame PA2950) of P.
      aeruginosa. Using DNA microarrays, we found that the transcriptional levels of
      type II secretory system genes were significantly reduced in the pfm mutant
      strain. The type-II-dependent exoprotein LasB could not be secreted normally. The
      pfm gene was identified as a gene involved in bacterial protein secretion that
      was critical for the extracellular release of elastase in P. aeruginosa. The
      abilities to induce lung injury by wild-type and pfm mutant P. aeruginosa were
      evaluated in a murine acute lung infection model. The results showed that the
      pathogenicity and virulence of the pfm mutant strain was significantly reduced
      compared with that of the wild-type strain. The pfm gene and its expression
      product, as potential new drug targets against P. aeruginosa infection, have
      important research significance.

PMID- 21950739
TI  - Surveillance culture monitoring of double-balloon enteroscopy reprocessing with
      high-level disinfection.
AB  - BACKGROUND: Inadequate reprocessing of double-balloon enteroscopy (DBE) or of
      endoscopic accessories may result in iatrogenic infections and present a risk to
      public health. AIM: To use microbiological surveillance culture monitoring (SCM)
      to assess the adequacy of high-level disinfection (HLD) with standard
      reprocessing procedures of DBE. MATERIALS AND METHODS: We performed a prospective
      study on cultures collected from DBEs that had been treated by HLD by an
      automated endoscope washing machine (AEWM) decontamination cycle. This study
      included 42 cases with 57 cultures, which were collected consecutively between
      October 2009 and December 2010. In 31 cases, 31 cultures were collected from oral
      route DBE (mean patient age, 68.9 years), and in 23 cases, 26 cultures were
      collected from anal route DBE (mean patient age, 67.9 years). The results
      obtained were compared with those of our previous study of SCM on gastroscopy
      (GS) and colonoscopy (CS). The samples were collected by flushing 50 mL sterile
      distilled water into the suction channel and collecting the flow-through in a
      sterile container. The samples were then incubated at 37  degrees C and examined
      for bacterial growth. RESULTS: Before HLD, the positive culture rate was 83.9%
      (26/31) for the oral route DBE and 100% (26/26) for the anal route DBE (P =
      0.0406). After HLD, the positive culture rate was 12.9% (4/31) for the oral route
      DBE and 19.2% (5/26) for the anal route DBE (P > 0.05). A linear trend
      relationship was found between positive SCM and the length and category of
      diagnostic instruments--GS, CS, oral route DBE and anal route DBE. CONCLUSIONS:
      Surveillance culture monitoring is a useful method to assess the effectiveness of
      HLD reprocessing of DBE. Machine washing may not achieve complete disinfection.
      Using AEWM regularly is mandatory to minimize cross-contamination and to ensure
      quality assurance. Additional procedures are necessary to employ for the longer
      and anal route DBE.

PMID- 21950740
TI  - Is there a significance of histamine in the control of the human male sexual
      response?
AB  - Although histamine has been suggested to be involved in the control of male
      sexual function, including the induction of penile erection, its role in the
      human corpus cavernosum penis is still poorly understood. The aim of our study
      was to evaluate the course of histamine plasma levels through different stages of
      sexual arousal in the systemic and cavernous blood of healthy male subjects.
      Thirty four (34) healthy men were exposed to erotic stimuli to elicit penile
      erection. Blood was aspirated from the corpus cavernosum and a cubital vein
      during the penile conditions flaccidity, tumescence, rigidity and detumescence.
      Blood was also collected in the post-ejaculatory period. Plasma levels of
      histamine (ng ml(-1)) were determined by means of a radioimmunoassay. Histamine
      slightly decreased in the cavernous blood when the penis became tumescent. During
      rigidity, histamine decreased further but remained unaltered in the phase of
      detumescence and after ejaculation. In the systemic circulation, no alterations
      were observed with the initiation or termination of penile erection, whereas a
      significant drop was registered following ejaculation. Results are not in favour
      of the hypothesis of an excitatory role of histamine in the control of penile
      erection. Nevertheless, the amine might mediate biological events during the post
      ejaculatory period.

PMID- 21950742
TI  - Are non-traditional CD4(+) CD69(+) CD25(-)  regulatory T cells involved in
      disease progression of human hepatocellular carcinoma?

PMID- 21950741
TI  - Effects of statins on cholestasis: good, bad or indifferent?

PMID- 21950743
TI  - Wire-guided cannulation for endoscopic retrograde cholangiopancreatography: now
      is the time to teach trainees a standardized technique.

PMID- 21950744
TI  - Molecular change that distinguishes traditional serrated adenomas from sessile
      serrated adenomas.

PMID- 21950745
TI  - Human dendritic cells transfected with amplified MUC1 mRNA stimulate cytotoxic T
      lymphocyte responses against pancreatic cancer in vitro.
AB  - BACKGROUND AND AIM: Mucin (MUC) 1 is an epithelial cell glycoprotein that is
      aberrantly overexpressed in many adenocarcinomas, including pancreatic cancer
      (PC), providing an ideal tumor-associated antigen and target for immunotherapy.
      In this study, we investigated whether the cytotoxic T lymphocytes (CTLs) induced
      by dendritic cells (DCs) transfected with amplified MUC1 mRNA could respond
      against PC in vitro. METHODS: Amplified mRNA encoding MUC1 were transfected into
      DCs using electroporation with an optimized setting and the MUC1 expression were
      evaluated by quantitative real-time polymerase chain reaction and Western blot.
      The MUC1 specific CTL responses were measured using the standard chromium 51
      (51Cr)-release assays and the interferon-gamma release assay. RESULTS: Dendritic
      cells could be transfected with amplified MUC1 mRNA efficiently. The transfected
      DCs were remarkably effective in stimulating MUC1-specific CTL responses in
      vitro. The function of MUC1 specific CTLs, induced by MUC1 mRNA-transfected DCs,
      was restricted by major histocompatibility complex (MHC) class I antigen
      presentation. CONCLUSION: The CTL responses stimulated by DCs transfected with
      MUC1 mRNA could only recognize and lyse HLA-A2+/MUC1+ PC and other target cells
      under restriction by MHC class I-specific antigen presentation, providing a
      preclinical rationale for using MUC1 as a target structure for immunotherapeutic
      strategies against PC.

PMID- 21950746
TI  - Complex non-invasive fibrosis models are more accurate than simple models in non
      alcoholic fatty liver disease.
AB  - BACKGROUND AND AIM: Significant hepatic fibrosis is prognostic of liver morbidity
      and mortality in non-alcoholic fatty liver disease (NAFLD); however, it remains
      unclear whether non-invasive fibrosis models can determine this end-point. We
      therefore compared the accuracy of simple bedside versus complex fibrosis models
      across a range of fibrosis in a multi-centre NAFLD cohort. METHODS: Simple (APRI,
      BARD) and complex (Hepascore, Fibrotest, FIB4) fibrosis models were calculated in
      242 NAFLD subjects undergoing liver biopsy. Significant (F2-4) and advanced
      fibrosis (F3,4) were defined using Kleiner criteria. Models were compared using
      area under the receiver operator characteristic curves (AUC). Cut-offs were
      determined by Youden Index or 90% predictive values. RESULTS: For significant
      fibrosis, non-invasive fibrosis models had modest accuracy (AUC 0.707-0.743) with
      BARD being least accurate (AUC 0.609, P < 0.05 vs others). Using single cut-offs,
      sensitivities and predictive values were < 80%; using two cut-offs, > 75% of
      subjects fell within indeterminate ranges. Simple models had significantly more
      subjects within indeterminate ranges than complex models (99.1-100% vs 82.1-84.4%
      respectively, P < 0.05 for all). For advanced fibrosis, complex models were more
      accurate than BARD (AUC 0.802-0.858 vs 0.701, P < 0.05). Using two cut-offs,
      complex models had fewer individuals within indeterminate ranges than BARD (11.1
      32.3% vs 70.7%, P < 0.01 for all). For cirrhosis, complex models had higher AUC
      values than simple models. CONCLUSIONS: In NAFLD subjects, non-invasive models
      have modest accuracy for determining significant fibrosis and have predictive
      values less than 90% in the majority of subjects. Complex models are more
      accurate than simple bedside models across a range of fibrosis.

PMID- 21950747
TI  - Education and imaging. Gastrointestinal: rare presentation of appendicitis:
      Amyand's hernia.

PMID- 21950748
TI  - Education and imaging. Gastrointestinal: metastatic ocular melanoma causing
      massive hepatomegaly.

PMID- 21950749
TI  - Education and imaging. Gastrointestinal: beware of the painful rectum.

PMID- 21950750
TI  - Education and imaging. Hepatobiliary and pancreatic: traumatic hepatic
      arterioportal fistula.

PMID- 21950751
TI  - Education and imaging. Hepatobiliary and pancreatic: splenic vein aneurysm with
      portal hypertension and hypersplenism.

PMID- 21950760
TI  - Short-term control of maize cell and root water permeability through plasma
      membrane aquaporin isoforms.
AB  - Although it is widely accepted that aquaporins are involved in the regulation of
      root water uptake, the role of specific isoforms in this process is poorly
      understood. The mRNA expression and protein level of specific plasma membrane
      intrinsic proteins (PIPs) were analysed in Zea mays in relation to cell and root
      hydraulic conductivity. Plants were analysed during the day/night period, under
      different growth conditions (aeroponics/hydroponics) and in response to short
      term osmotic stress applied through polyethylene glycol (PEG). Higher protein
      levels of ZmPIP1;2, ZmPIP2;1/2;2, ZmPIP2;5 and ZmPIP2;6 during the day coincided
      with a higher water permeability of root cortex cells during the day compared
      with night period. Similarly, plants which were grown under aeroponic conditions
      and which developed a hypodermis ('exodermis') with Casparian bands, effectively
      forcing more water along a membranous uptake path across roots, showed increased
      levels of ZmPIP2;5 and ZmPIP1;2 in the rhizodermis and exodermis. When PEG was
      added to the root medium (2-8 h), expression of PIPs and cell water permeability
      in roots increased. These data support a role of specific PIP isoforms, in
      particular ZmPIP1;2 and ZmPIP2;5, in regulating root water uptake and cortex cell
      hydraulic conductivity in maize.

PMID- 21950762
TI  - Immunolocalization of aquaporin-5 in normal human skin and hypohidrotic skin
      diseases.
AB  - Aquaporin (AQP)-5 has been shown to be expressed in the secretory parts of mouse,
      rat and horse sweat glands. However, the precise localization of AQP-5 in normal
      and diseased human skin has not been fully determined. The aim of the present
      study was to further clarify the immunolocalization of AQP-5 in normal human skin
      and hypohidrotic skin diseases. Normal human scalp skin and biopsies from skin
      affected by hypohidrotic diseases were analyzed for AQP-5 and/or dermcidin
      expression by immunohistochemistry, immunofluorescence and/or
      immunoelectronmicroscopy. AQP-5 was expressed on the apical and basolateral
      plasma membranes of the clear cells in eccrine sweat coils, but not in ductal
      components or apocrine glands. Numbers of AQP-5-positive coils in the secretory
      part of eccrine sweat glands were decreased in Sjogren's syndrome, but not in
      skin affected by idiopathic segmental anhidrosis or idiopathic pure sudomotor
      failure. AQP-5 was mostly localized to the plasma membranes of clear cells in the
      secretory coils of eccrine sweat glands, suggesting that it plays a role in
      producing the primary sweat fluid.

PMID- 21950761
TI  - Quantitative proteomic identification of the BRCA1 ubiquitination substrates.
AB  - Mutation of the BRCA1 tumor suppressor gene predisposes women to hereditary
      breast and ovarian cancers. BRCA1 forms a heterodimer with BARD1. The BRCA1/BARD1
      heterodimer has ubiquitin ligase activity, considered to play crucial roles in
      tumor suppression and DNA damage response. Nevertheless, relevant BRCA1
      substrates are poorly defined. We have developed a new approach to systematically
      identify the substrates of ubiquitin ligases by identifying proteins that display
      an enhanced incorporation of His-tagged ubiquitin upon ligase coexpression; using
      this method, we identified several candidate substrates for BRCA1. These include
      scaffold attachment factor B2 (SAFB2) and Tel2 as well as BARD1. BRCA1 was found
      to enhance SAFB protein expression and induce Tel2 nuclear translocation.
      Identification of the ubiquitination substrates has been a major obstacle to
      understanding the functions of ubiquitin ligases. The quantitative proteomics
      approach we devised for the identification of BRCA1 substrates will facilitate
      the identification of ubiquitin ligase-substrate pairs.

PMID- 21950763
TI  - Chronotropic incompetence and abnormal heart rate recovery early after left
      ventricular assist device implantation.
AB  - BACKGROUND: Chronotropic response to exercise and heart rate recovery immediately
      after exercise (HRR(1) ) are valid prognostic markers in patients with chronic
      heart failure (CHF). The aim of this study was to evaluate heart rate profile
      during and after exercise in CHF patients early after left ventricular assist
      device (LVAD) implantation. METHODS: We enrolled seven stable consecutive CHF
      patients (five males, mean age: 45 +/- 16 years) after 1 month of LVAD (HeartMate
      II; Thoratec Corp, Pleasanton, CA, USA) implantation, seven healthy subjects, and
      14 patients with advanced HF (HF control group) who performed an incremental
      symptom-limited cardiopulmonary exercise testing (CPET). CHF patients performed
      CPET at 1 and 3 months after LVAD. HRR(1) was defined as the HR difference from
      peak to 1 minute after exercise and chronotropic response to exercise as the
      chronotropic reserve ([CR, %]=[peak HR-resting HR/220-age-resting HR]* 100).
      RESULTS: LVAD patients 3 months after implantation had a significantly different
      HR profile during exercise compared to healthy controls, with significantly lower
      CR (57 +/- 31 vs 90 +/- 14, %, P < 0.001) and HRR(1) (14 +/- 6 vs 28 +/- 8, bpm,
      P < 0.01). HR profile during exercise did not significantly change 1 and 3 months
      after LVAD implantation. There was no statistical difference compared to HF
      control group and LVAD group regarding cardiopulmonary parameters. CONCLUSIONS:
      LVAD patients present an impaired CR and an abnormal HRR(1) after implantation,
      indicating significant cardiac autonomic abnormalities. These alterations seem to
      remain unaltered 3 months after LVAD implantation.

PMID- 21950764
TI  - alpha-Hemoglobin stabilizing protein: a modulating factor in thalassemias?
AB  - alpha-Hemoglobin stabilizing protein (AHSP) is a small protein of 102 residues
      induced by GATA-1, Oct-1- and EKLF. It is synthesized at a high level in the red
      blood cell precursors and acts as a chaperone protecting the alpha-hemoglobin
      (alpha-Hb) chains against precipitation. alpha-Hemoglobin stabilizing protein
      forms a heterodimer complex with alpha-Hb, then displaying modified oxygen
      binding kinetics. In the absence of AHSP, alpha-Hb oxidizes and precipitates
      within the erythrocyte precursors of bone marrow leading to apoptosis and
      defective erythropoiesis. Several alpha-Hb variants with a structural
      abnormality, frequently located in the contact area between alpha-Hb and AHSP,
      exhibit instability and a thalassemia-like syndrome when they are associated with
      another alpha-thalassemia (alpha-thal) determinant. We suggest that this disorder
      could result from a disturbed interaction between the abnormal alpha-Hb chains
      and AHSP. Hb Groene Hart (Pro119>Ser) was one of the first examples in which we
      observed this abnormality. We later verified this mechanism in a list of several
      variants, now considered as being nondeletional alpha-thalassemias. Conversely,
      it was hypothesized from studies on knock-out mice, that a defect affecting AHSP
      could cause a thalassemia-like syndrome. This was supported in man by studies
      showing that a decreased expression of AHSP linked to specific genetic clades
      could act as a modulating factor in some thalassemia phenotypes. It was also
      supported by our observation of a family from Southeast Asia, in which a child
      homozygous for an AHSP mutant (Val56>Gly) displayed, in his first year of life, a
      moderate thalassemia syndrome. This mutant AHSP was expressed in vitro and
      demonstrated by biochemical and biophysical studies to display a clear defective
      interaction with alpha-Hb, which could support the hypothesis that the reb blood
      cell (RBC) disorders of the child resulted from this abnormality. It therefore
      appears that AHSP is a factor with a key role in the formation of Hb tetramers
      and that structural abnormalities, either on the alpha-Hb or on the AHSP, may act
      as a thalassemia modulating factor.

PMID- 21950766
TI  - How I manage neonatal thrombocytopenia.
AB  - Although neonatal thrombocytopenia (platelet count < 150*10(9) /l) is a common
      finding in hospital practice, a careful clinical history and examination of the
      blood film is often sufficient to establish the diagnosis and guide management
      without the need for further investigations. In preterm neonates, early-onset
      thrombocytopenia (<72h) is usually secondary to antenatal causes, has a
      characteristic pattern and resolves without complications or the need for
      treatment. By contrast, late-onset thrombocytopenia in preterm neonates (>72h) is
      nearly always due to post-natally acquired bacterial infection and/or necrotizing
      enterocolitis, which rapidly leads to severe thrombocytopenia (platelet
      count<50*10(9) /l). Thrombocytopenia is much less common in term neonates and the
      most important cause is neonatal alloimmune thrombocytopenia (NAIT), which
      confers a high risk of perinatal intracranial haemorrhage and long-term
      neurological disability. Prompt diagnosis and transfusion of human platelet
      antigen-compatible platelets is key to the successful management of NAIT. Recent
      studies suggest that more than half of neonates with severe thrombocytopenia
      receive platelet transfusion(s) based on consensus national or local guidelines
      despite little evidence of benefit. The most pressing problem in management of
      neonatal thrombocytopenia is identification of safe, effective platelet
      transfusion therapy and controlled trials are urgently needed.

PMID- 21950767
TI  - An evaluation of P50 paired-click methodologies.
AB  - The utility of P50 paired-click measures is limited by their unestablished
      reliability, unknown effects of time, and long protocol. This study measured
      within-session reliability, temporal course, effect of varying interpair interval
      (IPI), and peak definition and ratio calculation methods on P50 paired-click
      measures in healthy participants. Results indicate higher reliability for
      difference (ICC=.72) than ratio (ICC=.44) method; when P50 peaks are defined as
      baseline-to-peak than peak-to-peak; time-related changes; and comparable P50
      paired-click measures at long (9 s) and short (3-7 s) IPIs. After controlling for
      time effects, P50 paired-click measures are relatively reliable within-session
      and are best measured using the difference method and defined as baseline-to-peak
      amplitude; time effects must be taken into account when measuring P50 paired
      click measures in a long paradigm; and IPI can be shortened in studies with
      healthy samples.

PMID- 21950768
TI  - Anomalous plutonium isotopic ratios in sediments of Lake Qinghai from the Qinghai
      Tibetan Plateau, China.
AB  - The vertical profiles of (239+240)Pu and (137)Cs activities and (240)Pu/(239)Pu
      isotopic ratios are determined for three sediment cores of Lake Qinghai from the
      Qinghai-Tibetan Plateau, China, and compared with those in sediments of another
      three lakes (Lakes Bosten, Sugan, and Shuangta), the only existing ones closest
      to Lop Nor area, China's nuclear weapons test site in the northwestern part of
      the country. The mean inventory of 47.7 +/- 18.7 MBq km(-2) for (239+240)Pu
      activity in Lake Qinghai is comparable to the average value of global fallout
      expected at the same latitude, yet the mean inventory of 1112.0 +/- 78.0 MBq km(
      2) for (137)Cs is slightly lower than that of global fallout. Anomalously low
      (240)Pu/(239)Pu isotopic ratios (0.038-0.125) were found in the 3-6.5 cm deep
      sediment layers, indicating the trace Pu input from early nuclear weapons
      research activities at Atomic City in the lake's watershed during the 1950-60s.
      Model calculation indicated that the Pu input accounted for approximately 5-16%
      of the total Pu inventory. The observation of low (240)Pu/(239)Pu ratio in the
      deep sediment layer provided a new time marker for recent sediment dating in the
      lake and around the area. The results are of great significance to the further
      understanding of sources, records, and environmental impacts of global and
      regional nuclear activities in the environment and provide important
      chronological information for further studies on the water eutrophication process
      and climatic change, and reconstruction of pollution history of organic
      contaminants and heavy metals in the watershed of Lake Qinghai.

PMID- 21950769
TI  - Long-term outcomes of distant metastasis from differentiated thyroid carcinoma.
AB  - BACKGROUND:   The aim of this study was to identify the prognostic factors of
      long-term survival and optimal therapeutic protocol for patients with distant
      metastasis secondary to differentiated thyroid carcinoma (DTC). METHODS:   A
      retrospective review of 1665 patients with DTC treated at a regional tertiary
      hospital in Taiwan between 1986 and 2010 was performed. Among them, 207 patients
      were found to have distant metastasis. For a long-term outcome survey, 126
      patients that had received at least 5 years (mean 9.6 +/- 5.2 years) of follow-up
      after the diagnosis of distant metastasis were analysed for this study.
      Prognostic factor analysis included age, sex, histology, disease stage, type of
      surgical procedure, site of metastatic foci, (131) I avidity of tumour,
      thyroglobulin (Tg) level and accumulated therapeutic dose of radioiodine (RAI).
      RESULTS:   The mean age at diagnosis of distant metastasis was 46.4 +/- 17.2
      years. The female-to-male ratio was 2.1:1. The 10- and 15-year survival rates
      were 70.6% and 64.9%, respectively. The independent predictors of survival were
      younger age, surgical dissection of neck lymph nodes (LNs) and low TSH-stimulated
      Tg level (<400 MUg/l) at the discovery of metastasis. Most cases of resolved
      (131) I-avid disease (79.2%) and disease-free remission (87.5%) received a
      cumulative dose no >600 mCi of (131) I. The mean cumulative doses of (131) I in
      both deceased and living patients were similar. CONCLUSION:   The prognosis of
      patients with distant metastasis from DTC within this study was found to be
      favourable. Survival may be improved by surgical dissection of neck LNs, but
      repeated (131) I therapy >600 mCi is not advised unless there is a high
      probability that it would benefit the patient.

PMID- 21950771
TI  - Multicentric reticulohistiocytosis masquerading as dermatomyositis: similar and
      different features.

PMID- 21950770
TI  - In vitro phosphinate methylation by PhpK from Kitasatospora phosalacinea.
AB  - Radical S-adenosyl-L-methionine, cobalamin-dependent methyltransferases have been
      proposed to catalyze the methylations of unreactive carbon or phosphorus atoms in
      antibiotic biosynthetic pathways. To date, none of these enzymes has been
      purified or shown to be active in vitro. Here we demonstrate the activity of the
      P-methyltransferase enzyme, PhpK, from the phosalacine producer Kitasatospora
      phosalacinea. PhpK catalyzes the transfer of a methyl group from methylcobalamin
      to 2-acetylamino-4-hydroxyphosphinylbutanoate (N-acetyldemethylphosphinothricin)
      to form 2-acetylamino-4-hydroxymethylphosphinylbutanoate (N
      acetylphosphinothricin). This transformation gives rise to the only carbon
      phosphorus-carbon linkage known to occur in nature.

PMID- 21950772
TI  - Casein kinase II alpha subunits affect multiple developmental and stress
      responsive pathways in Arabidopsis.
AB  - Casein kinase II (formerly known as CK2), a ubiquitous Ser/Thr kinase, plays
      critical roles in all higher organisms including plants. The CK2 holoenzyme
      consists of two catalytic alpha subunits and two regulatory beta subunits. The
      Arabidopsis genome has four alpha subunit and four beta subunit genes, and
      members of both the alpha and beta subunit families have been shown to be
      localized in the cytoplasm, nucleus and also in chloroplasts. However, the
      biological roles of CK2 subunits have not been fully characterized yet. Here we
      identified T-DNA insertion mutants in three alpha subunit genes (alpha1, alpha2
      and alpha3) and made double and triple mutants. The CK2 alpha1alpha2alpha3 triple
      mutants displayed reduced CK2 activity compared with wild-type seedlings.
      Phenotypic characterization showed that CK2 alpha1alpha2alpha3 triple mutants are
      late flowering under both long- and short-day conditions. Genes encoding floral
      integrators are differentially regulated in the triple mutant compared with the
      wild-type plants. CK2 alpha1alpha2alpha3 triple mutants also displayed reduced
      hypocotyl growth, smaller cotyledon size and a reduced number of lateral roots
      compared with wild-type seedlings under light. Abscisic acid-induced blockage of
      seed germination and cotyledon greening is reduced in CK2 alpha subunit mutants
      in an additive manner. Moreover, CK2 alpha subunit mutants are also hyposensitive
      to a NaCl-induced blockage of seed germination. Taken together, these data
      suggest that CK2 alpha subunits affect diverse developmental and stress
      responsive pathways in Arabidopsis.

PMID- 21950773
TI  - Sleep disturbances and insulin resistance.
AB  - The causes and risk factors of insulin resistance remain insufficiently
      understood. After taking into account the important roles of adiposity, age, sex
      and race/ethnicity, up to 50% of the individual variability in insulin resistance
      remains unexplained. In recent years, evidence has accumulated to support a role
      for sleep disturbances, including insufficient sleep, poor sleep quality and
      insomnia, and obstructive sleep apnoea, as independent risk factors for the
      development and exacerbation of insulin resistance. The present review summarizes
      the evidence. We will start with a brief introduction to sleep and its disorders
      and then examine in succession the role of the three major types of sleep
      disturbances of modern society, namely insufficient sleep, poor sleep quality
      and/or insomnia and obstructive sleep apnoea. Insulin resistance is a hallmark of
      the polycystic ovary syndrome, the most common endocrine pathology in women, and
      the last section of this review will discuss the role of obstructive sleep apnoea
      in the insulin resistance and metabolic disturbances of polycystic ovary
      syndrome.

PMID- 21950774
TI  - A unique two-way approach for the validation of total antioxidant capacity of
      serum samples.
AB  - BACKGROUND: The human body is constantly exposed to a large variety of reactive
      oxygen species that are implicated in many pathophysiological conditions
      (atherosclerosis, cancer, neurodegenerative diseases etc.). Monitoring the
      antioxidant status of biological fluids could be used as an early warning sign
      'biomarker' of possible disease onset. However, although several methods have
      been developed, questionable sensitivity, unreliability and non-reproducibility
      hamper all, making it difficult to have an internationally accepted standardized
      method. This study presents and demonstrates the remarkable ability of a newly
      developed antioxidant capacity assay method based on tetramethoxy azobismethylene
      quinone (TMAMQ) to measure the total antioxidant capacity of serum samples using
      three complimentary approaches. DESIGN: Using an UV-Vis spectroscopy and oxygen
      sensor, the reduction of TMAMQ by serum antioxidants was compared to either the
      formation of syringaldazine or consumption of oxygen. RESULTS: After adding a
      fraction of human serum, 4.01 MUM TMAMQ was reduced to syringaldazine from a
      stock of 11.74 MUM TMAMQ. Subsequent addition of laccase resulted in the
      oxidation of the formed syringaldazine back to TMAMQ resulting in an increase in
      TMAMQ concentration to 11.71 MUM (re-establishing almost the same initial
      concentration of TMAMQ) while consuming 1.04 MUM molecular oxygen. CONCLUSIONS:
      The reduction of TMAMQ by serum samples is directly proportional to the
      consumption of oxygen and the formation of syringaldazine. This means that either
      the formation of syringaldazine or oxygen consumption can be used to validate or
      confirm data obtained through monitoring TMAMQ reduction.

PMID- 21950775
TI  - Depressive symptoms among Chinese nurses: prevalence and the associated factors.
AB  - AIM:   This article is a report of exploration of depressive symptoms and the
      associated factors among Chinese nurses working at public city hospitals.
      BACKGROUND:   Hospital nurses are known to work in psychologically and physically
      demanding work environment, which may lead to depressive symptoms. However,
      little research has been done to address this problem in Chinese nurses. METHODS:
      A cross-sectional survey was carried out in seven randomly selected city
      hospitals of Liaoning Province, northeast of China in 2009. Depressive symptoms
      of the nurses were measured with the Chinese version of the Center for
      Epidemiologic Studies Depression Scale. Job Content Questionnaire and the effort
      reward imbalance, demographic features, life style and work conditions were
      measured as the related factors. RESULTS:   A total of 1592 nurses participated
      in the study and the effective response rate was 79.5%. The prevalence of
      depressive symptoms among the nurses was 61.7% (n = 886), of whom 74.9% (n = 664)
      had mild depressive symptoms. Multivariate logistic regression analysis showed
      that lower job rank, higher over commitment, alcohol consumption, worse nurse
      patient relationship and higher education background were positively associated
      with depressive symptoms, whereas supervisor support, taking regular meals, doing
      physical exercises, higher skill discretion and higher job satisfaction were
      negatively associated with depressive symptoms. CONCLUSION:   More than half of
      the Chinese nurses had depressive symptoms. As depressive symptoms may adversely
      affect quality of life and quality of care, consultation for the nurses with
      healthy life styles, work stress coping techniques and advice to administrator to
      improve social aspects of the work environment might be helpful to reduce the
      depressive symptoms in nurses.

PMID- 21950776
TI  - The future of cognitive neurorehabilitation.
AB  - Cognitive neurorehabilitation is rooted both in the cognitive function being
      treated and the neural substrates underlying that ability. Recent progress in
      understanding both brain (in particular brain plasticity) and the complexities of
      behaviour imply a promising future for cognitive neurorehabilitation. The
      manuscripts in this issue focuse on advances in the use of non-invasive brain
      stimulation (NIBS) as a tool for cognitive neurorehabilitation. This paper
      presents a broader context in which to understand the importance and potential of
      this specific approach. Achieving the promise requires theoretical and
      experimental rigour including selection of relevant outcome measures, and
      understanding of the complexities of individual patients. Success will depend on
      our ability to integrate knowledge and approaches.

PMID- 21950778
TI  - Extracorporeal perfusion of the swine uterus: effect of human seminal plasma.
AB  - The active transport of sperm through the female genital tract is a very
      important factor in the fertilisation process. There is conflicting evidence as
      to whether seminal plasma has a positive or a negative effect on reproductive
      performance regarding the sperm transport in the female genital tract. In this
      study, we investigated if the perfused swine uterus is an appropriate model to
      study the effect of human seminal plasma on uterine contractility. It was found
      that repeated application of human seminal plasma caused a significantly higher
      rise in pressure and frequency of contractions in perfused swine uteri compared
      to buffer [a 1.8-fold and 1.5-fold pressure rise (Deltat1SP, P = 0.025;
      Deltat2SP, P = 0.004)] after the first and second application of seminal plasma
      respectively, and even a 2-fold pressure rise after the third application with a
      statistical significance of P = 0.007. The pressure rise caused by the seminal
      plasma over the entire period of application was calculated using a mathematical
      programme and was represented by the integral of the pressure curve over time.
      This perfusion model as well as the use of pressure-time integrals is suitable
      for patho-physiological studies of the uterus.

PMID- 21950777
TI  - Characteristics of concatemeric GABA(A)  receptors containing alpha4/delta
      subunits expressed in Xenopus oocytes.
AB  - BACKGROUND AND PURPOSE: GABA(A) receptors mediate both synaptic and extrasynaptic
      actions of GABA. In several neuronal populations, alpha4 and delta subunits are
      key components of extrasynaptic GABA(A) receptors that strongly influence
      neuronal excitability and could mediate the effects of neuroactive agents
      including neurosteroids and ethanol. However, these receptors can be difficult to
      study in native cells and recombinant delta subunits can be difficult to express
      in heterologous systems. EXPERIMENTAL APPROACH: We engineered concatemeric
      (fused) subunits to ensure delta and alpha4 subunit expression. We tested the
      pharmacology of the concatemeric receptors, compared with a common synaptic-like
      receptor subunit combination (alpha1 +beta2 +gamma2L), and with free-subunit
      alpha4/delta receptors, expressed in Xenopus oocytes. KEY RESULTS: delta-beta2 
      alpha4 +beta2-alpha4 cRNA co-injected into Xenopus oocytes resulted in GABA-gated
      currents with the expected pharmacological properties of alpha4/delta-containing
      receptors. Criteria included sensitivity to agonists of different efficacy,
      sensitivity to the allosteric activator pentobarbital, and modulation of agonist
      responses by DS2 (4-chloro-N-[2-(2-thienyl)imidazo[1,2-a]pyridine-3-yl benzamide;
      a delta-selective positive modulator), furosemide, and Zn(2+) . We used the
      concatemers to examine neurosteroid sensitivity of extrasynaptic-like, delta
      containing receptors. We found no qualitative differences between extrasynaptic
      like receptors and synaptic-like receptors in the actions of either negative or
      positive neurosteroid modulators of receptor function. Quantitative differences
      were explained by the partial agonist effects of the natural agonist GABA and by
      a mildly increased sensitivity to low steroid concentrations. CONCLUSIONS AND
      IMPLICATIONS: The neurosteroid structure-activity profile for alpha4/delta
      containing extrasynaptic receptors is unlikely to differ from that of synaptic
      like receptors such as alpha1/beta2/gamma2-containing receptors.

PMID- 21950779
TI  - Bifocals in Down syndrome study (BiDS): analysis of video recorded sessions of
      literacy and visual perceptual skills.
AB  - PURPOSE: In this longitudinal study, a group of school children with Down
      syndrome (DS) and reduced accommodation were prescribed bifocals and followed to
      investigate the impact of bifocal spectacles on early literacy and visual
      perceptual skills. The natural progression of early literacy skills in this
      population along with the changes with bifocals, described by monthly subtest
      scores and the time taken to complete literacy and visual perceptual tasks, are
      reported. METHODS: Fourteen children with DS, aged eight to 18 years, were
      followed for five months with single vision lenses; 11 were prescribed bifocals
      based on their accommodative ability and followed for another five months. A
      battery of reading and visual perceptual tests was administered before and after
      prescription of bifocals. Monthly subtests of similar tasks were administered to
      measure progress. All the visits were videotaped to determine the time taken for
      the child to complete each task. RESULTS: There was no significant measurable
      natural progression of early literacy skills in this group of participants on the
      Word Identification (WI) subtest (Repeated Measures ANOVA, F [4, 24]=1.377, p =
      0.271) and Dolch sight words (RMANOVA F [4, 24]= 0.344, p = 0.846). In contrast,
      once bifocals were prescribed there was significant improvement in the scores of
      the monthly subtests (p = 0.050, 0.025 and 0.023 for WI, Dolch sight words and
      numbers, respectively) and the rate of progress in monthly scores improved for WI
      (p = 0.008). Repeated measures Analysis of Variance showed a significant decrease
      in the completion times with bifocals for the WI test in the full battery of
      tests (p = 0.0015). There was significant correlation between the improvement in
      focus with bifocals and the decrease in completion time for the WI task (p =
      0.004). CONCLUSIONS: This study demonstrates no significant natural progression
      over a five-month period in the group of participants with Down syndrome;
      however, with bifocals, faster and improved performance on some literacy skills
      was observed. We recommend that bifocals be considered in children with Down
      syndrome presenting with inadequate accommodation to optimise their educational
      potential.

PMID- 21950780
TI  - Why use automated office blood pressure measurements in clinical practice?
AB  - Automated office blood pressure (AOBP) measurement with the patient resting alone
      in a quiet examining room can eliminate the white-coat effect associated with
      conventional readings taken by manual sphygmomanometer. The key to reducing the
      white-coat response appears to be multiple blood pressure (BP) readings taken in
      a non-observer office setting, thus eliminating any interaction that could
      provoke an office-induced increase in BP. Furthermore, AOBP readings have shown a
      higher correlation with the mean awake ambulatory BP compared with BP readings
      recorded in routine clinical practice. Although there is a paucity of studies
      connecting AOBP with organ damage, AOBP values were recently found to be equally
      associated with left ventricular mass index as those of ambulatory BP. This
      concludes that in contrast to routine manual office BP, AOBP readings compare
      favourably with 24-hour ambulatory BP measurements in the appraisal of cardiac
      remodelling and, as such, could be complementary to ambulatory readings in a way
      similar to home BP measurements.

PMID- 21950781
TI  - Direct renin inhibition: from pharmacological innovation to novel therapeutic
      opportunities.
AB  - Nowadays, social and economic burden related to cardiovascular and renal diseases
      still remains extremely high, although there has been a dramatic improvement of
      diagnostic options and therapeutic strategies reported in the last 30 years. The
      progressively higher attention towards integrated pharmacological strategies,
      which are able to interfere with different pathophysiological mechanisms, has
      certainly led to better control of cardiovascular and renal diseases. In view of
      the large involvement of the renin-angiotensin system (RAS) in the vast majority
      of pathophysiological mechanisms leading to the development and progression of
      cardiovascular and renal diseases, it can be easily understood why it has been
      long viewed as the 'ideal' target for the pharmacological treatment of several
      clinical conditions. Recently, besides the well known therapeutic approaches for
      RAS blockade, based on the use of ACE inhibitors, angiotensin II type 1 receptor
      antagonists (angiotensin receptor blockers [ARBs]) and aldosterone antagonists,
      both the scientific and medical community have focused their attention on a novel
      therapeutic option. In 2007, aliskiren, the first compound of a new drug class,
      the direct renin inhibitors (DRIs), has become available for clinical use, being
      a novel and innovative therapeutic option. Aliskiren is able to interfere with
      the enzymatic activity of renin by blocking the catalytic site of the molecule
      and inducing an 'upstream' RAS blockade. This leads to a modulation of the
      biological properties of renin, thus resulting in the missed cleavage of
      angiotensinogen to angiotensin I. Aliskiren has demonstrated antihypertensive
      efficacy comparable or even superior to that of other classes of antihypertensive
      drugs, both in monotherapy and in combination therapies. Its safety and
      tolerability are comparable with those of other antihypertensive drug classes and
      almost similar to placebo. In addition, it has been demonstrated to reduce
      progression of cardiac and renal organ damage in addition to ACE inhibitors or
      ARBs. An ambitious and large clinical trial programme specifically designed for
      this innovative antihypertensive drug will evaluate the efficacy of aliskiren in
      terms of reduced incidence of major cardiovascular and renal outcomes in patients
      with hypertension and cardiovascular disease, besides the use of optimal
      (standard) therapeutic strategies, including ACE inhibitors and ARBs.

PMID- 21950782
TI  - Efficacy and safety of treatment of hypertensive patients with fixed combination
      perindopril/indapamide up to 10/2.5 mg: results of the FALCO FORTE programme.
AB  - BACKGROUND: The objective of the FALCO FORTE programme was to demonstrate the
      efficacy and safety of 3 months of therapy with the fixed combination
      perindopril/indapamide in hypertensive patients in everyday medical practice.
      DESIGN AND METHODS: Patients with blood pressure >140/90 mmHg or with blood
      pressure >130/85 mmHg and three or more risk factors were prescribed
      perindopril/indapamide 2.5/0.625 mg or 5/1.25 mg. Dosage could be increased to
      10/2.5 mg at any time during the study. RESULTS: Of the 2327 patients included,
      69% of patients had been unsuccessfully treated with other antihypertensives,
      4.6% had not tolerated previous antihypertensive treatments, and 26.8% were newly
      diagnosed hypertensive patients. Roughly half the cohort was at high or very high
      cardiovascular risk. After 3 months of therapy, systolic blood pressure decreased
      from 156.9 +/- 13.7 to 132.3 +/- 10.6 mmHg (p < 0.0001) and diastolic blood
      pressure from 94.9 +/- 8.2 to 81.3 +/- 6.3 mmHg (p < 0.0001). Target blood
      pressure was reached by 87.1% of patients. Similar changes from baseline were
      observed in patients with diabetes mellitus, metabolic syndrome or left
      ventricular hypertrophy (p < 0.0001). When blood pressure decreases were analysed
      by dose, changes from baseline increased with increasing doses.
      Perindopril/indapamide was well tolerated with no significant changes in
      laboratory parameters being observed. Quality of life improved significantly.
      CONCLUSIONS: Therapy with fixed combination perindopril/indapamide was effective
      and well tolerated in a wide range of patients.

PMID- 21950795
TI  - How linker's modification controls swelling properties of highly flexible
      iron(III) dicarboxylates MIL-88.
AB  - A series of organically modified iron(III) terephthalate MIL-88B and iron(III)
      4,4'-biphenyl dicarboxylate MIL-88D flexible solids have been synthesized and
      characterized through a combination of X-ray diffraction, IR spectroscopy, and
      thermal analysis (MIL stands for Material from Institut Lavoisier). The swelling
      amplitude of the highly flexible MOFs tuned by introducing functional groups onto
      the phenyl rings shows a clear dependence on the steric hindrance and on the
      number of groups per aromatic ring. For instance, while the introduction of four
      methyl groups per spacer in dried MIL-88B results in a large permanent porosity,
      introducing two or four methyl groups in MIL-88D allows an easier pore opening in
      the presence of liquids without drastically decreasing the swelling magnitude.
      The influence of the degree of saturation of the metal center and the nature of
      the solvent on the swelling is also discussed. Finally, a computationally
      assisted structure determination has led to a proposal of plausible structures
      for the closed (dried) and open forms of modified MIL-88B and MIL-88D and to
      evaluation of their framework energies subject to the nature of the functional
      groups.

PMID- 21950797
TI  - The efficiency of the CO2-concentrating mechanism during single-cell C4
      photosynthesis.
AB  - The photosynthetic efficiency of the CO(2)-concentrating mechanism in two forms
      of single-cell C(4) photosynthesis in the family Chenopodiaceae was
      characterized. The Bienertioid-type single-cell C(4) uses peripheral and central
      cytoplasmic compartments (Bienertia sinuspersici), while the Borszczowioid single
      cell C(4) uses distal and proximal compartments of the cell (Suaeda
      aralocaspica). C(4) photosynthesis within a single-cell raises questions about
      the efficiency of this type of CO(2) -concentrating mechanism compared with the
      Kranz-type. We used measurements of leaf CO(2) isotope exchange (Delta(13) C) to
      compare the efficiency of the single-cell and Kranz-type forms of C(4)
      photosynthesis under various temperature and light conditions. Comparisons were
      made between the single-cell C(4) and a sister Kranz form, S. eltonica[NAD malic
      enzyme (NAD ME) type], and with Flaveria bidentis[NADP malic enzyme (NADP-ME)
      type with Kranz Atriplicoid anatomy]. There were similar levels of Delta(13) C
      discrimination and CO(2) leakiness (Phi) in the single-cell species compared with
      the Kranz-type. Increasing leaf temperature (25 to 30  degrees C) and light
      intensity caused a decrease in Delta(13) C and Phi across all C(4) types.
      Notably, B. sinuspersici had higher Delta(13) C and Phi than S. aralocaspica
      under lower light. These results demonstrate that rates of photosynthesis and
      efficiency of the CO(2) -concentrating mechanisms in single-cell C(4) plants are
      similar to those in Kranz-type.

PMID- 21950796
TI  - Autoactivated KlPDR1 gene in the control of multidrug resistance in 
      Kluyveromyces lactis.
AB  - The KlPDR1 gene encodes a zinc finger transcription factor that has recently been
      shown to be involved in the control of multidrug resistance of Kluyveromyces
      lactis . In this work, we provide evidence that the K. lactis KlPDR1 gene is
      under positive autoregulation by KlPdr1p, which plays a role in the activation of
      the main multidrug resistance transporter gene KlPDR5. Electrophoretic mobility
      shift assays, as well as the use of gusA reporter constructs, enabled us to
      identify the 5'-tataTCCGGGTAactt-3' sequence motif in the KlPDR1 promoter (in the
      position -326 to -319 bp) as the PDRE (pleiotropic drug responsive element) for
      the binding of KlPdr1p. The drug sensitivity of Klpdr1Delta mutant cells was
      complemented by introducing the plasmid-born KlPDR1 gene. The KlPdr1p activated
      the expression of the P(KlPDR1)-gusA fusion gene, and the expression of the
      KlPDR1 gene was induced by fluconazole. The PDRE was also found in the promoter
      of KlPDR5, a gene encoding the ATP-dependent efflux pump responsible for the drug
      resistance phenomenon in K. lactis.

PMID- 21950798
TI  - Dual atrioventricular nodal nonreentrant tachycardia: a systematic review.
AB  - BACKGROUND: Dual atrioventricular nodal nonreentrant tachycardia (DAVNNT) is a
      relatively uncommon supraventricular tachycardia. The clinical characteristics
      and optimal management strategies are not well described. METHODS: A systematic
      review of all reported cases of DAVNNT was performed. Articles were included if
      they described spontaneous tachycardias resulting from 1:2 atrioventricular (AV)
      conduction as a result of two AV nodal pathways. Data sources included PubMed
      from 1950 to January 2011, article bibliographies, and the Google internet search
      engine. RESULTS: Ultimately, 44 citations that reported 49 cases met inclusion
      criteria. DAVNNT is being reported with increasing frequency. Clinical
      characteristics were assessed using the 44 cases reported in the English
      language. Palpitations were the most common presenting symptom (89%). The
      majority of patients had a significant delay until the correct diagnosis was made
      (77%). The most common specific mistaken diagnosis was atrial fibrillation (32%)
      and five patients were diagnosed after referral for pulmonary vein isolation.
      Nine reports described association with a tachycardia-mediated cardiomyopathy.
      Catheter ablation has successfully treated all reported cases since 1994.
      CONCLUSIONS: DAVNNT is an uncommon arrhythmia being reported with increasing
      frequency. It is commonly mistaken for atrial fibrillation and is associated with
      a reversible tachycardia-mediated cardiomyopathy. Catheter ablation of the slow
      AV nodal pathway is curative and appears to be the therapy of choice, although
      more systematic study is required.

PMID- 21950799
TI  - Dermoscopy of the pigmented fungiform papillae of the tongue.
AB  - This is the report of two patients with pigmented fungiform papillae of the
      tongue, a benign condition, more frequent in dark skinned patients. We present
      the dermoscopic findings of this condition, which resembled rose petals.

PMID- 21950800
TI  - Delineation of subtelomeric deletion of the long arm of chromosome 6.
AB  - Pure subtelomeric deletion of the long arm of chromosome 6 is rare. The frequency
      of this deletion accounts for approximately 0.05% of subjects with intellectual
      disability and developmental delay with or without dysmorphic features. Common
      phenotypes associated with this deletion include intellectual disability,
      developmental delay, dysmorphic features, seizure, hypotonia, microcephaly and
      hypoplasia of the corpus callosum. The smallest overlapped region is
      approximately 0.4 Mb, and contains three known genes. Of these genes, TBP has
      been considered as a plausible candidate gene for the phenotype in patients with
      a subtelomeric 6q deletion. Analysis of the breakpoints in 14 cases revealed a
      potential common breakpoint interval 8.0-9.0 Mb from the chromosome 6q terminus
      where the FRA6E fragile site exists and the PARK2 gene is located. This suggests
      that breakage at the FRA6E fragile site may be the mechanism behind chromosome 6q
      subtelomeric deletion in some of the cases.

PMID- 21950801
TI  - Quantitative neuroproteomics of an in vivo rodent model of focal cerebral
      ischemia/reperfusion injury reveals a temporal regulation of novel
      pathophysiological molecular markers.
AB  - Cerebral ischemia or stroke, an acute neurological injury lacking an effective
      therapy, is the second leading cause of death globally. The unmet need in stroke
      research is to identify viable targets and to understand their interplay during
      the temporal evolution of ischemia/reperfusion (I/R) injury. Here we report a
      temporal signature of the ischemic hemisphere revealed by the isobaric tag for
      relative and absolute quantification (iTRAQ)-based 2D-LC-MS/MS strategy in an in
      vivo middle cerebral artery occlusion (MCAO) model of focal cerebral I/R injury.
      To recapitulate clinical stroke, two hours of MCAO was followed by 0, 4, and 24 h
      of reperfusion to capture ischemia with an acute and subacute durations of
      reperfusion injury. The subsequent iTRAQ experiment identified 2242 proteins from
      the ischemic hemisphere with <1.0% false discovery rate. Data mining revealed
      that (1) about 2.7% of detected proteins were temporally perturbed having an
      involvement in the energy metabolism (Pygb, Atp5b), glutamate excitotoxicity
      (Slc1a3, Glud1), neuro-inflammation (Tf, C3, Alb), and cerebral plasticity (Gfap,
      Vim, Gap43); (2) astrocytes participated actively in the neurometabolic coupling
      underlining the importance of a cerebro-protective rather than a neuro-protective
      approach; and (3) hyper-acute yet progressive opening of the blood brain barrier
      (BBB), accompanied by stimulation of an innate immune response and late
      activation of a regenerative response, which provides an extended therapeutic
      window for intervention. Several regulated proteins (Caskin1, Shank3, Kpnb1,
      Uchl1, Mtap6, Epb4.1l1, Apba1, and Ube1x) novel in the context of stroke were
      also discovered. In conclusion, our result supports a dynamic multitarget therapy
      rather than the traditional approach of a unilateral and sustained modulation of
      a single target to address the phasic regulation of an ischemic proteome.

PMID- 21950802
TI  - Health, human rights, and performance: interrupted stories.

PMID- 21950803
TI  - The analysis of zero-inflated count data: beyond zero-inflated Poisson
      regression.
AB  - Infrequent count data in psychological research are commonly modelled using zero
      inflated Poisson regression. This model can be viewed as a latent mixture of an
      "always-zero" component and a Poisson component. Hurdle models are an alternative
      class of two-component models that are seldom used in psychological research, but
      clearly separate the zero counts and the non-zero counts by using a left
      truncated count model for the latter. In this tutorial we revisit both classes of
      models, and discuss model comparisons and the interpretation of their parameters.
      As illustrated with an example from relational psychology, both types of models
      can easily be fitted using the R-package pscl.

PMID- 21950804
TI  - Barrett's esophagus: prevalence-incidence and etiology-origins.
AB  - Although the prevalence of Barrett's esophagus (BE) is rising no data exist for
      racial minorities on prevalence in the general population. Minorities have a
      lower prevalence than Caucasians, and yet age, smoking, abdominal obesity, and
      Helicobacter pylori are all risk factors. Metabolic changes induced by
      adipocytokines and the apparently strong association between obesity, central
      adiposity, and BE may lead to reconsideration of some aspects of the natural
      history of BE. There is lack of experimental evidence on acid sensitivity and BE,
      which is hyposensitive compared to esophageal reflux disease. Reactive nitrogen
      and oxygen species lead to impaired expression of tumor suppressor genes, which
      can lead to cancer development; thus, antioxidants may be protective.
      Gastroesophageal reflux disease may be considered an immune-mediated disease
      starting at the submucosal layer; the cytokine profile of the mucosal immune
      response may explain the different outcome of gastroesophageal reflux.

PMID- 21950805
TI  - Barrett's esophagus: genetic and cell changes.
AB  - The following includes commentaries on how genetic code of Barrett's esophagus
      (BE) patients, the mechanisms for GERD-induced esophageal expression of caudal
      homeobox, and the development of Barrett's metaplasia are increasingly better
      known, including the role of stromal genes in oncogenesis. Additional lessons
      have been learned in vitro models in nonneoplastic cell lines, yet there are
      limitations to what can be expected from BE-derived cell lines. Other topics
      discussed include clonal diversity in Barrett's esophagus; the application of
      peptide arrays to clinical samples of metaplastic mucosa; proliferation and
      apoptosis of Barrett's cell lines; tissue biomarkers for neoplasia; and
      transcription factors associated with BE.

PMID- 21950806
TI  - Barrett's esophagus: clinical features, obesity, and imaging.
AB  - The following includes commentaries on clinical features and imaging of Barrett's
      esophagus (BE); the clinical factors that influence the development of BE; the
      influence of body fat distribution and central obesity; the role of
      adipocytokines and proinflammatory markers in carcinogenesis; the role of body
      mass index (BMI) in healing of Barrett's epithelium; the role of surgery in
      prevention of carcinogenesis in BE; the importance of double-contrast
      esophagography and cross-sectional images of the esophagus; and the value of
      positron emission tomography/computed tomography.

PMID- 21950807
TI  - Barrett's esophagus: endoscopic diagnosis.
AB  - This collection of summaries on endoscopic diagnosis of Barrett's esophagus (BE)
      includes the best endoscopic markers of the extent of BE; the interpretation of
      the diagnosis of ultra-short BE; the criteria for endoscopic grading; the
      sensitivity and specificity of endoscopic diagnosis; capsule and magnifying
      endoscopy; narrow band imaging; balloon cytology; the distinction between focal
      and diffuse dysplasia; the techniques for endoscopic detection of dysplasia and
      the grading systems; and the difficulty of interpretation of inflammatory or
      regenerative changes.

PMID- 21950808
TI  - Barrett's esophagus: histology and immunohistology.
AB  - The following on histology and immunohistology of Barrett's esophagus (BE)
      includes commentaries on the various difficulties remaining in reaching a
      consensus on the definition of BE; the difficulties in the characterization of
      intestinal and cardiac mucosa, and in the role of submucosal glands in the
      development of BE; the importance of a new monoclonal antibody to recognize
      esophageal intestinal mucosa; the importance of pseudo goblet cells; the best
      techniques for the endoscopic detection of Barrett's epithelium; and the
      biomarkers for identification of patients predisposed to the development of BE.

PMID- 21950809
TI  - Barrett's esophagus: proton pump inhibitors and chemoprevention I.
AB  - The following on proton pump inhibitors and chemoprevention in Barrett's
      esophagus includes commentaries on normalization of esophageal refluxate; the
      effects of 5-HT(4)  agonists on EGF secretion and of lubripristone on chloride
      channels agents; the role of Campylobacter toxin production; the deleterious
      effects of unconjugated bile acids; the role of baclofen in nonacid reflux; the
      threshold for adequate esophageal acid exposure; the effects of proton pump
      inhibitor (PPI) therapy on normalization of esophageal pH and on cell
      proliferation; the role of the phenotype of cellular proliferation on the effects
      of PPI therapy; and the value of Symptom Index and Symptom Association
      Probability in the evaluation of potential response to treatment.

PMID- 21950810
TI  - Barrett's esophagus: proton pump inhibitors and chemoprevention II.
AB  - The following on proton pump inhibitors (PPIs) and chemoprevention in relation to
      Barrett's esophagus includes commentaries on 48-h pH monitoring, pH-impedence,
      bile acid testing, dyspepsia, long/short segment Barrett's esophagus, nonerosive
      reflux disease (NERD), functional heartburn, dual-release delivery PPIs,
      immediate-release PPIs, long-term PPI use, prokinetic agents, obesity, baclofen,
      nocturnal acid breakthrough, nonsteroidal anti-inflammatory drugs (NSAIDs), and
      new PPIs.

PMID- 21950811
TI  - Barrett's esophagus: endoscopic treatments I.
AB  - The following on endoscopic treatments of Barrett's esophagus includes
      commentaries on indications for endoscopic treatments; endo-luminal plication
      procedures; the cellular modifications induced by the endoscopic ablation
      therapies; eradication by banding without resection; the evaluation of complete
      ablation; recurrence after ablation; association of antireflux surgery;
      radiofrequency ablation; and nondysplastic Barrett's esophagus.

PMID- 21950813
TI  - Barrett's esophagus: surgical treatments.
AB  - The following on surgical treatments for Barrett's esophagus includes
      commentaries on the indications for antireflux surgery after medical treatment;
      the effects of the various procedures on the lower esophageal sphincter; the role
      of impaired esophageal motility and delayed gastric emptying in the choice of the
      surgical procedure; indications for associated highly selective vagotomy,
      duodenal switch, and gastric electrical stimulation; therapeutic strategies for
      detection and treatment of shortened esophagus; the role of antireflux surgery on
      the regression of metaplastic mucosa and the risk of malignant progression; the
      detection of asymptomatic reflux brfore bariatric surgery; the role of non-GERD
      symptoms on the results of surgery; and the indications of Collis gastroplasty
      and choice of the type of fundoplication.

PMID- 21950812
TI  - Barrett's esophagus: endoscopic treatments II.
AB  - The following on endoscopic treatments of Barrett's esophagus includes
      commentaries on animal experiments on cryotherapy; indications for cryotherapy,
      choice of dosimetry, number of sessions, and role in Barrett's esophagus and
      adenocarcinoma; recent technical developments of RFA technology and long-term
      effects; the comparative effects of diverse ablation procedures and the rate of
      recurrence following treatment; and the indications for treatment of dysplasia
      and the role of radiofrequency ablation.

PMID- 21950814
TI  - Barrett's esophagus: surveillance and reversal.
AB  - The following on surveillance and reversal of Barrett's esophagus (BE) includes
      commentaries on criteria for surveillance even when squamous epithelium stains
      normally with a variety of biomarkers; the long-term follow-up of surgery versus
      endoscopic ablation of BE; the recommended surveillance intervals in patients
      without dysplasia; the sampling problems related to anatomic changes following
      fundoplication; the value of tissue spectroscopy and optical coherence
      tomography; the cost-effectiveness of biopsy protocols for surveillance; the
      quality of life of Barrett's patients; and risk stratification and surveillance
      strategies.

PMID- 21950815
TI  - Barrett's esophagus: progression to adenocarcinoma and markers.
AB  - The following on progression to adenocarcinoma and markers of Barrett's esophagus
      includes commentariess on the expression of claudin 4 in Barrett's
      adenocarcinoma; the role of acid and bile salts; the role of insulin-like growth
      factor; the value of reactive oxygen species; the importance of abnormal
      methylation; genetic alterations in stromal cells and genomic changes in the
      epithelial cells; the value of confocal laser endomicroscopy for the subsurface
      analysis of the mucosa; indications for statins as adjuvant chemotherapeutic
      agent; the sequence of molecular events in malignant progression in Barrett's
      mucosa; and the value of the macroscopic markers and of p53 mutations.

PMID- 21950817
TI  - Barrett's esophagus: treatments of adenocarcinomas I.
AB  - The following on the treatments of adenocarcinomas in Barrett's esophagus
      contains commentaries on endo mucosal resection; choice between other ablative
      therapies; the remaining genetic abnormalities following stepwise endoscopic
      mucosal resection and possible recurrences; the Fotelo-Fotesi PDT; the CT TNM
      classification of early stages of Barrett's carcinoma; the indications of
      lymphadenectomy in intramucosal cancer; the differences in lymph node yield in
      transthoracic versus transhiatal dissection; video-assisted lymphadenectomy; and
      the importance of the length of proximal esophageal resectipon; and indications
      of sentinel node dissection.

PMID- 21950816
TI  - Barrett's esophagus: prevalence and incidence of adenocarcinomas.
AB  - The following on prevalence and incidence of adenocarcinomas in Barrett's
      esphophagus (BE) includes commentaries on the mechanisms of a potential
      protective effect of proton pump inhibitors (PPIs) on progression of BE to high
      grade dysplasia; evaluation of the role of PPIs in decreasing the risk of
      degeneration; the geographical variations of incidence of BE; the role of the
      nonmorphologic biomarkers; the relationship between length of BE and development
      of cancer; the confounding factors in incidence rates of BE; the role of the
      increase of cell differentiation and apoptosis induced by PPIs in the diminution
      of cancer risk; the frequency of occult neoplastic foci and unsuspected invasive
      cancer in surgical specimens; the influence on the indications of endoscopic
      therapy; the overestimation of regression in surgical series; attempts to
      evaluate the reasons for variations of cancer incidence in the literature; and
      progress in screening and surveillance for BE.

PMID- 21950819
TI  - Barrett's esophagus: natural history.
AB  - The following on the natural history of Barrett's esophagus (BE) includes
      commentary on histological sequences of the development of Barrett mucosa; the
      transformation of esophageal cells from squamous to columnar phenotype; the
      stages of natural history of dysplasia; the difficulties of predicting
      progression of dysplasia to adenocarcinoma; the preferable biopsy protocols; the
      role of Helicobacter pylori infection and gastric atrophy in the risk of BE; the
      value of decrease of proton pump inhibitor efficacy following eradication of H.
      pylori; the place of antireflux surgery in the natural history of BE; the newest
      procedures for the endoscopic detection of early neoplasia; and the essential
      importance of a good understanding of the natural history for the best management
      of high-grade dysplasia.

PMID- 21950818
TI  - Barrett's esophagus: treatments of adenocarcinomas II.
AB  - The following topics are explored in this collection of commentaries on
      treatments of adenocarcinomas related to Barrett's esophagus: the importance of
      intraoperative frozen sections of the margins for the detection of high
      dysplasia; the preferable way for sentinel node dissection; the current role of
      robotic surgery and of video-endoscopic approach; the value of the Siewert's
      classification of adenocarcinomas; the indications of two-step esophagectomy; the
      evaluation of pathological complete response; the role of PET scan in staging and
      response assessment; the role of p53 in the selection of adenocarcinomas
      patients; chemotherapy regimens for adenocarcinomas; the use of monoclonal
      antibodies in the control of cell proliferation; he attempt to define a stage
      specific strategy, and the possible indications of selective therapy; and changes
      in mortality rates from esophageal cancer.

PMID- 21950820
TI  - Molecular aspects of esophageal development.
AB  - The following on molecular aspects of esophageal development contains
      commentaries on esophageal striated myogenesis and transdifferentiation;
      conversion from columnar into stratified squamous epithelium in the mouse
      esophagus; the roles for BMP signaling in the developing esophagus and
      forestomach; and evidence of a direct conversion from columnar to stratified
      squamous cells in the developing esophagus.

PMID- 21950821
TI  - Esophageal stem cells and 3D-cell culture models.
AB  - The following on esophageal stem cells and 3D-cell culture models contains
      commentaries on metaplasia through transdifferentiation and through stem cells;
      transcription factors that may determine an intestinal-like phenotype; the in
      vitro, organotypic cell culture models; and the role of stem cells in Barrett's
      esophagus and its dysplastic progression.

PMID- 21950822
TI  - The esophagogastric junction.
AB  - The following discussion of the esophagogastric junctions includes commentaries
      on the three component structures of the sphincteric segment between the stomach
      and the esophagus; the pressure contributions from the three sphincteric
      components in normal subjects and in gastroesophageal reflux (GERD) patients; the
      mechanism of action of endoscopic plication to determine the underlying
      pathophysiology of GERD; and in vitro muscle strip studies of defects within the
      gastroesophageal sphincteric segment potentially leading to GERD.

PMID- 21950823
TI  - Distensibility testing of the esophagus.
AB  - The following contains commentaries on distensibility testing using the
      functional lumen imaging probe (FLIP); the use of the distention test of the
      esophageal body in the clinic diagnosis of noncardiac chest pain; the functional
      lumen imaging in gastroesophageal reflux disease-impaired esophagogastric
      junction; a multimodal pain model for the esophagus; the rationale for
      distensibility testing; and further developments in standardized distension
      protocols.

PMID- 21950824
TI  - Mechanism-based evaluation and treatment of esophageal disorders.
AB  - The following on mechanism-based evaluation and treatment of esophageal
      disordered contains commentaries on multimodal stimulation to study esophageal
      function, the neurophysiological and autonomous assessment of sensory
      abnormalities, and the clinical value of the novel diagnostic combinations to
      propose a mechanically targeted treatment.

PMID- 21950825
TI  - High-resolution manometry.
AB  - The following presents commentaries on the interest of high-resolution manometry
      for understanding the anatomy and physiology of the esophagogastric junction; the
      subtypes of achalasia, as diagnosed by high-resolution manometry; the interest of
      high-resolution manometry in the evaluation of dysphagia following
      fundoplication; and the appropriate clinical protocol for high-resolution
      manometry.

PMID- 21950826
TI  - Testing for gastroesophageal reflux in the 21st century.
AB  - The following on testing for gastroesophageal reflux in the 21st century contains
      commentaries on wireless pH monitoring; extension of pH recording duration to 48
      or 96 h; extraesophageal GERD syndromes, diagnosis paradigms, and related
      investigating tools; off- or on-PPI reflux monitoring in the preoperative
      setting; and the potential influence of PPIs on reflux parameters.

PMID- 21950827
TI  - The new requirements of endoscopy.
AB  - The following on new requirements of endoscopy contains commentaries on the risk
      of infection in endoscopy, the need to eliminate contamination, and the use of a
      disposable system in transnasal endoscopy.

PMID- 21950828
TI  - Esophageal disease: updated information on inflammation.
AB  - The following on esophageal disease provides updated information the mucosal
      defense against acid and acid-pepsin injury; the roles of platelet activating
      factor, mast cells, proinflammatory cytokines, and chemokines in inflammation;
      differences and similarities in erosive and nonerosive esophagitis; acid and
      vanilloid receptors in esophageal mucosa; and bile acid receptors in esophageal
      epithelium.

PMID- 21950829
TI  - Esophageal disease and pathology.
AB  - The following on esophageal disease and pathology contains commentaries on the
      varied definitions of Barrett's esophagus (BE); the optimal biopsy strategy in
      BE; reliable biomarkers for progression to neoplasia in BE; and the role of bone
      marrow stem cells in the morphogenesis of Barrett's esophagus.

PMID- 21950830
TI  - Molecular mechanisms of Barrett's esophagus and adenocarcinoma.
AB  - The following on molecular mechanisms of Barrett's esophagus and adenocarcinoma
      contains commentaries on the mechanism of bile and gastric acid induced damage;
      the roles of BMP-4 and CDX-2 in the development of intestinal metaplasia; the
      transcription factors driving intestinalization in Barrett's esophagus; the
      contribution of bone marrow to metaplasia and adenocarcinoma; activation and
      inactivation of transcription factors; and a novel study design targeting
      molecular pathways in Barrett's esophagus.

PMID- 21950831
TI  - Barrett's esophagus and animal models.
AB  - The following on Barrett's esophagus (BE) and animal models contains commentaries
      on the factors of BE carcinogenesis; a duodenoesophageal reflux model;
      translation of targeted therapies for esophageal adenocarcinoma; and novel target
      regimens selected through a proteomics screen.

PMID- 21950832
TI  - Esophageal disease in pediatrics.
AB  - The following on esophageal disease in pediatrics contains commentaries on
      acquisition of neuromuscular maturation; physiology of esophageal peristaltic and
      sphincteric reflexes; implications for clinical practice; and conditions that
      predispose to severe gastroesophageal reflux disease (GERD) in children with
      potential risk for esophageal cancer.

PMID- 21950833
TI  - Barrett's esophagus registries.
AB  - The following on Barrett's esophagus registries contains commentaries on the data
      sets to be included, organizational issues, and the demographic, lifestyle, and
      diagnostic differences between the United States and Europe. The importance of
      collaborative studies is also discussed.

PMID- 21950834
TI  - Interventional endoscopy and single incision surgery.
AB  - The following on interventional endoscopy and single incision surgery contains
      commentaries on transluminal endoscopic esophageal surgery, flexible endoscopy,
      triangulation, advanced flexible operating platforms, experimental
      transesophageal procedures, and para- and intra-esophageal endoscopic surgery.

PMID- 21950835
TI  - Introduction to Barrett's Esophagus.

PMID- 21950836
TI  - Impact of porous media grain size on the transport of multi-walled carbon
      nanotubes.
AB  - Nanoparticles possess unique physical, electrical, and chemical properties which
      make them attractive for use in a wide range of consumer products. Through their
      manufacturing, usage, and eventual disposal, nanoparticles are expected to
      ultimately be released to the environment after which point they may pose
      environmental and human health risks. One critical component of understanding and
      modeling those potential risks is their transport in the subsurface environment.
      This study investigates the mobility of one important nanoparticle (multi-walled
      carbon nanotubes or MWCNTs) through porous media, and makes the first
      measurements on the impact of mean collector grain size (d(50)) on MWCNT
      retention. Results from one-dimensional column experiments conducted under
      various physical and chemical conditions coupled with results of numerical
      modeling assessed the suitability of traditional transport models to predict
      MWCNT mobility. Findings suggest that a dual deposition model coupled with site
      blocking greatly improves model fits compared to traditional colloid filtration
      theory. Of particular note is that the MWCNTs traveled through porous media
      ranging in size from fine sand to silt resulting in normalized concentrations of
      MWCNTs in the effluent in excess of 60% of the influent concentration.

PMID- 21950837
TI  - Self-assembly and reconfigurability of shape-shifting particles.
AB  - Reconfigurability of two-dimensional colloidal crystal structures assembled by
      anisometric particles capable of changing their shape were studied by molecular
      dynamics computer simulation. We show that when particles change shape on cue,
      the assembled structures reconfigure into different ordered structures,
      structures with improved order, or more densely packed disordered structures, on
      faster time scales than can be achieved via self-assembly from an initially
      disordered arrangement. These results suggest that reconfigurable building blocks
      can be used to assemble reconfigurable materials, as well as to assemble
      structures not possible otherwise, and that shape shifting could be a promising
      mechanism to engineer assembly pathways to ordered and disordered structures.

PMID- 21950838
TI  - Atrial fibrillation and hyperthyroidism: relation between transoesophageal
      markers of a thrombogenic milieu and clinical risk factors for thromboembolism.
AB  - Hyperthyroidism is a questionable risk factor for thromboembolism among patients
      with atrial fibrillation. OBJECTIVE:   To correlate clinical risk factors for
      thromboembolism from a group of patients with atrial fibrillation related to
      hyperthyroidism with transoesophageal echocardiography (TOE) markers of a
      thrombogenic milieu. DESIGN:   Clinical risk factors for thromboembolism, thyroid
      hormonal status, time since diagnosis of hyperthyroidism and TOE markers of a
      thrombogenic milieu were assessed in consecutive patients with atrial
      fibrillation related to hyperthyroidism. The following TOE parameters were
      assessed to define the presence of thrombogenic milieu: dense spontaneous echo
      contrast, thrombi or left atrial appendage blood flow velocities <0.20 m/s.
      Clinical risk factors for thromboembolism were based on CHADS(2) (Cardiac
      failure, Hypertension, Age, Diabetes and Stroke) classification. PATIENTS:   This
      study included 31 consecutive patients aged between 18 and 65 years with atrial
      fibrillation related to hyperthyroidism scheduled for TOE. RESULTS:  
      Thrombogenic milieu was present in 14 of 31 (45.2%) patients. The thyroid status
      could not predict the presence of a thrombogenic milieu. Despite low CHADS(2)
      score of 0/1, 6 of 13 (46.1%) patients had a thrombogenic milieu, whereas 10 of
      18 (55.6%) patients with score >=2 had none. The probability of having a
      thrombogenic milieu did not correlate with the number of clinical risk factors.
      CONCLUSION:   Among patients younger than 65 years of age with atrial
      fibrillation related to hyperthyroidism, there is no association between clinical
      risk factors with TOE markers of a thrombogenic milieu. TOE adds useful
      information that may affect antithrombotic therapy guided by clinical risk
      classification.

PMID- 21950839
TI  - Functional consequences of the creation of an Asp-His-Fe triad in a 3/3 globin.
AB  - The proximal side of dehaloperoxidase-hemoglobin A (DHP A) from Amphitrite ornata
      has been modified via site-directed mutagenesis of methionine 86 into aspartate
      (M86D) to introduce an Asp-His-Fe triad charge relay. X-ray crystallographic
      structure determination of the metcyano forms of M86D [Protein Data Bank (PDB)
      entry  3MYN ] and M86E (PDB entry  3MYM ) mutants reveal the structural origins
      of a stable catalytic triad in DHP A. A decrease in the rate of H(2)O(2)
      activation as well as a lowered reduction potential versus that of the wild-type
      enzyme was observed in M86D. One possible explanation for the significantly lower
      activity is an increased affinity for the distal histidine in binding to the heme
      Fe to form a bis-histidine adduct. Resonance Raman spectroscopy demonstrates a pH
      dependent ligation by the distal histidine in M86D, which is indicative of an
      increased trans effect. At pH 5.0, the heme Fe is five-coordinate, and this
      structure resembles the wild-type DHP A resting state. However, at pH 7.0, the
      distal histidine appears to form a six-coordinate ferric bis-histidine
      (hemichrome) adduct. These observations can be explained by the effect of the
      increased positive charge on the heme Fe on the formation of a six-coordinate low
      spin adduct, which inhibits the ligation and activation of H(2)O(2) as required
      for peroxidase activity. The results suggest that the proximal charge relay in
      peroxidases regulate the redox potential of the heme Fe but that the trans effect
      is a carefully balanced property that can both activate H(2)O(2) and attract
      ligation by the distal histidine. To understand the balance of forces that
      modulate peroxidase reactivity, we studied three M86 mutants, M86A, M86D, and
      M86E, by spectroelectrochemistry and nuclear magnetic resonance spectroscopy of
      (13)C- and (15)N-labeled cyanide adducts as probes of the redox potential and of
      the trans effect in the heme Fe, both of which can be correlated with the
      proximity of negative charge to the N(delta) hydrogen of the proximal histidine,
      consistent with an Asp-His-Fe charge relay observed in heme peroxidases.

PMID- 21950840
TI  - Bipolar molecules with high triplet energies: synthesis, photophysical, and
      structural properties.
AB  - This article sheds new light on the interplay of electronic and conformational
      effects in luminescent bipolar molecules. A series of carbazole/1,3,4-oxadiazole
      hybrid molecules is described in which the optoelectronic properties are
      systematically varied by substituent effects which tune the intramolecular
      torsion angles. The synthesis, photophysical properties, cyclic voltammetric
      data, X-ray crystal structures, and DFT calculations are presented. Excited state
      intramolecular charge transfer (ICT) is observed from the donor carbazole/2,7
      dimethoxycarbazole to the acceptor phenyl/diphenyloxadiazole moieties.
      Introducing more bulky substituents onto the diphenyloxadiazole fragment
      systematically increases the singlet and triplet energy levels (E(S) and E(T))
      and blue shifts the absorption and emission bands. The triplet excited state is
      located mostly on the oxadiazole unit. The introduction of 2,7-dimethoxy
      substituents onto the carbazole moiety lowers the value of E(S), although E(T) is
      unaffected, which means that the singlet-triplet gap is reduced (for 7bE(S) -
      E(T) = 0.61 eV). A strategy has been established for achieving unusually high
      triplet levels for bipolar molecules (E(T) = 2.64-2.78 eV at 14 K) while at the
      same time limiting the increase in the singlet energy.

PMID- 21950841
TI  - Giant cell arteritis with polymyalgia rheumatica associated with influenza
      vaccination.

PMID- 21950842
TI  - Implications of psychometric measurement for neuropsychological interpretation.
AB  - The purpose of this study is to examine the implications of various less-examined
      psychometric issues in the interpretation of neuropsychological data. Using a
      dataset of 4371 independent functioning and community-dwelling individuals who
      underwent neuropsychological evaluations, it was demonstrated that many common
      measures are not normally distributed. Non-normalized data can lead to
      erroneously pathological conclusions, particularly on the lower end of negatively
      skewed distributions. Another issue involves scatter. In line with previous
      studies, the current study found that approximately 67% of the 4371 participants
      showed discrepancies of three or more standard deviations between their highest
      and lowest test scores on 21 measures. However, in contradiction to the existing
      literature, in the current study mean scatter levels were relatively stable
      across increasing levels of intelligence. It is argued that this is due to
      regression to the mean. As an individual moves away from the population average
      in either direction, scores on other measures will regress from that person's IQ
      score toward the population mean. The lower a test correlates with IQ, the
      greater will be the regression toward the mean. Therefore the test battery in
      question must be considered during the interpretation process, in addition to the
      individual's premorbid IQ.

PMID- 21950844
TI  - Periodic force induced stabilization or destabilization of the denatured state of
      a protein.
AB  - We have studied the effects of an external sinusoidal force in protein folding
      kinetics. The externally applied force field acts on the each amino acid residues
      of polypeptide chains. Our simulation results show that mean protein folding time
      first increases with driving frequency and then decreases passing through a
      maximum. With further increase of the driving frequency the mean folding time
      starts increasing as the noise-induced hoping event (from the denatured state to
      the native state) begins to experience many oscillations over the mean barrier
      crossing time period. Thus unlike one-dimensional barrier crossing problems, the
      external oscillating force field induces both stabilization or destabilization of
      the denatured state of a protein. We have also studied the parametric dependence
      of the folding dynamics on temperature, viscosity, non-Markovian character of
      bath in presence of the external field.

PMID- 21950843
TI  - Gene network reconstruction identifies the authentic trans-prenyl diphosphate
      synthase that makes the solanesyl moiety of ubiquinone-9 in Arabidopsis.
AB  - Ubiquinone (coenzyme Q) is the generic name of a class of lipid-soluble electron
      carriers formed of a redox active benzoquinone ring attached to a prenyl side
      chain. The length of the latter varies among species, and depends upon the
      product specificity of a trans-long-chain prenyl diphosphate synthase that
      elongates an allylic diphosphate precursor. In Arabidopsis, this enzyme is
      assumed to correspond to an endoplasmic reticulum-located solanesyl diphosphate
      synthase, although direct genetic evidence was lacking. In this study, the
      reconstruction of the functional network of Arabidopsis genes linked to
      ubiquinone biosynthesis singled out an unsuspected solanesyl diphosphate synthase
      candidate--product of gene At2g34630--that, extraordinarily, had been shown
      previously to be targeted to plastids and to contribute to the biosynthesis of
      gibberellins. Green fluorescent protein (GFP) fusion experiments in tobacco and
      Arabidopsis, and complementation of a yeast coq1 knockout lacking mitochondrial
      hexaprenyl diphosphate synthase demonstrated that At2g34630 is also targeted to
      mitochondria. At2g34630 is the main--if not sole--contributor to solanesyl
      diphosphate synthase activity required for the biosynthesis of ubiquinone, as
      demonstrated by the dramatic (75-80%) reduction of the ubiquinone pool size in
      corresponding RNAi lines. Overexpression of At2g34630 gave up to a 40% increase
      in ubiquinone content compared to wild-type plants. None of the silenced or
      overexpressing lines, in contrast, displayed altered levels of plastoquinone.
      Phylogenetic analyses revealed that At2g34630 is the only Arabidopsis trans-long
      chain prenyl diphosphate synthase that clusters with the Coq1 orthologs involved
      in the biosynthesis of ubiquinone in other eukaryotes.

PMID- 21950845
TI  - Quantum and semiclassical theories for nonadiabatic transitions based on overlap
      integrals related to fast degrees of freedom.
AB  - Alternative treatments of quantum and semiclassical theories for nonadiabatic
      dynamics are presented. These treatments require no derivative couplings and
      instead are based on overlap integrals between eigenstates corresponding to fast
      degrees of freedom, such as electronic states. Derived from mathematical
      transformations of the Schrodinger equation, the theories describe nonlocal
      characteristics of nonadiabatic transitions. The idea that overlap integrals can
      be used for nonadiabatic transitions stems from an article by Johnson and Levine
      [Chem. Phys. Lett. 13, 168 (1972)]. Furthermore, overlap integrals in path
      integral form have been recently made available by Schmidt and Tully [J. Chem.
      Phys. 127, 094103 (2007)] to analyze nonadiabatic effects in thermal equilibrium
      systems. The present paper expands this idea to dynamic problems presented in
      path-integral form that involve nonadiabatic semiclassical propagators.
      Applications to one-dimensional nonadiabatic transitions have provided excellent
      results, thereby verifying the procedure. In principle these theories that are
      presented can be applied to multidimensional systems, although numerical costs
      could be quite expensive.

PMID- 21950846
TI  - Coarse-graining Brownian motion: from particles to a discrete diffusion equation.
AB  - We study the process of coarse-graining in a simple model of diffusion of
      Brownian particles. At a detailed level of description, the system is governed by
      a Brownian dynamics of non-interacting particles. The coarse-level is described
      by discrete concentration variables defined in terms of Delaunay cells. These
      coarse variables obey a stochastic differential equation that can be understood
      as a discrete version of a diffusion equation. We study different models for the
      two basic building blocks of this equation which are the free energy function and
      the diffusion matrix. The free energy function is shown to be non-additive due to
      the overlapping of cells in the Delaunay construction. The diffusion matrix is
      state dependent in principle, but for near-equilibrium situations it is shown
      that it may be safely evaluated at the equilibrium value of the concentration
      field.

PMID- 21950848
TI  - A semiclassical study of the thermal conductivity of low temperature liquids.
AB  - The conventional classical energy current auto-correlation function has been
      extended into a quantum mechanical version and then approximated by the
      linearized semiclassical initial value representation approach. Comparison of the
      thermal conductivity to simulation results shows that about 15% quantum
      correction to the classical molecular dynamics results for liquid neon are
      quantitatively predicted. For liquid para-hydrogen the quantum effects are
      sufficiently large that the linearized semiclassical approach is only 20%
      accurate, while for both liquid He(4) and He(3) the thermal conductivity
      disagrees by a factor of 2, although exchange effects appear to play a minor
      role.

PMID- 21950847
TI  - Generalized Langevin dynamics of a nanoparticle using a finite element approach:
      thermostating with correlated noise.
AB  - A direct numerical simulation (DNS) procedure is employed to study the thermal
      motion of a nanoparticle in an incompressible Newtonian stationary fluid medium
      with the generalized Langevin approach. We consider both the Markovian (white
      noise) and non-Markovian (Ornstein-Uhlenbeck noise and Mittag-Leffler noise)
      processes. Initial locations of the particle are at various distances from the
      bounding wall to delineate wall effects. At thermal equilibrium, the numerical
      results are validated by comparing the calculated translational and rotational
      temperatures of the particle with those obtained from the equipartition theorem.
      The nature of the hydrodynamic interactions is verified by comparing the velocity
      autocorrelation functions and mean square displacements with analytical results.
      Numerical predictions of wall interactions with the particle in terms of mean
      square displacements are compared with analytical results. In the non-Markovian
      Langevin approach, an appropriate choice of colored noise is required to satisfy
      the power-law decay in the velocity autocorrelation function at long times. The
      results obtained by using non-Markovian Mittag-Leffler noise simultaneously
      satisfy the equipartition theorem and the long-time behavior of the hydrodynamic
      correlations for a range of memory correlation times. The Ornstein-Uhlenbeck
      process does not provide the appropriate hydrodynamic correlations. Comparing our
      DNS results to the solution of an one-dimensional generalized Langevin equation,
      it is observed that where the thermostat adheres to the equipartition theorem,
      the characteristic memory time in the noise is consistent with the inherent time
      scale of the memory kernel. The performance of the thermostat with respect to
      equilibrium and dynamic properties for various noise schemes is discussed.

PMID- 21950850
TI  - Comparing different protocols of temperature selection in the parallel tempering
      method.
AB  - Parallel tempering Monte Carlo simulations have been applied to a variety of
      systems presenting rugged free-energy landscapes. Despite this, its efficiency
      depends strongly on the temperature set. With this query in mind, we present a
      comparative study among different temperature selection schemes in three lattice
      gas models. We focus our attention in the constant entropy method (CEM), proposed
      by Sabo et al. In the CEM, the temperature is chosen by the fixed difference of
      entropy between adjacent replicas. We consider a method to determine the entropy
      which avoids numerical integrations of the specific heat and other thermodynamic
      quantities. Different analyses for first- and second-order phase transitions have
      been undertaken, revealing that the CEM may be an useful criterion for selecting
      the temperatures in the parallel tempering.

PMID- 21950849
TI  - Zero field splitting of the chalcogen diatomics using relativistic correlated
      wave-function methods.
AB  - The spectrum arising from the (pi*)(2) configuration of the chalcogen dimers,
      namely, the X(2)1, a2, and b0(+) states, is calculated using wave-function theory
      based methods. Two-component (2c) and four-component (4c) multireference
      configuration interaction (MRCI) and Fock-space coupled cluster (FSCC) methods
      are used as well as two-step methods spin-orbit complete active space
      perturbation theory at 2nd order (SO-CASPT2) and spin-orbit difference dedicated
      configuration interaction (SO-DDCI). The energy of the X(2)1 state corresponds to
      the zero-field splitting of the ground state spin triplet. It is described with
      high accuracy by the 2- and 4-component methods in comparison with experiment,
      whereas the two-step methods give about 80% of the experimental values. The b0(+)
      state is well described by 4c-MRCI, SO-CASPT2, and SO-DDCI, but FSCC fails to
      describe this state and an intermediate Hamiltonian FSCC ansatz is required. The
      results are readily rationalized by a two-parameter model; Deltaepsilon, the pi*
      spinor splitting by spin-orbit coupling and K, the exchange integral between the
      pi(1)* and the pi(-1)* spinors with, respectively, angular momenta 1 and -1. This
      model holds for all systems under study with the exception of Po(2).

PMID- 21950851
TI  - Distribution-function approach to free energy computation.
AB  - Connections are explored between the free energy difference of two systems and
      the microscopic distribution functions of the energy difference. On the basis of
      a rigorous relationship between the energy distribution functions and the free
      energy, the scheme of error minimization is introduced to derive accurate and
      simple methods of free energy computation. A set of distribution-function
      approaches are then examined against model systems, and the newly derived methods
      exhibit state-of-art performance. It is shown that the notion of error
      minimization is powerful to improve the free energy calculation using
      distribution functions.

PMID- 21950852
TI  - Exploring the free energy surfaces of clusters using reconnaissance metadynamics.
AB  - A new approach is proposed for exploring the low-energy structures of small to
      medium-sized aggregates of atoms and molecules. This approach uses the recently
      proposed reconnaissance metadynamics method [G. A. Tribello, M. Ceriotti, and M.
      Parrinello. Proc. Natl. Acad. Sci. U.S.A. 107(41), 17509 (2010)] in tandem with
      collective variables that describe the average structure of the coordination
      sphere around the atoms/molecules. We demonstrate this method on both Lennard
      Jones and water clusters and show how it is able to quickly find the global
      minimum in the potential energy surface, while exploring the finite temperature
      free energy surface.

PMID- 21950853
TI  - Multiple time scale molecular dynamics for fluids with orientational degrees of
      freedom. I. Microcanonical ensemble.
AB  - We propose a new approach to eliminate the resonance instabilities inherent in
      multiple time step molecular dynamics simulations. The approach is developed
      within the microcanonical ensemble on the basis of an energy-constrained
      technique in the presence of orientational degrees of freedom. While the single
      and standard multiscale methods are restricted to small time steps of 5 and 8 fs,
      respectively, it is shown in simulations of water that the algorithms we have
      derived postpone the appearance of the instabilities to larger steps of about 16
      fs. Such steps are close to the upper theoretical limit of 20 fs peculiar to the
      microcanonical ensemble and can be used without affecting static and dynamical
      properties.

PMID- 21950854
TI  - Comparing ab initio density-functional and wave function theories: the impact of
      correlation on the electronic density and the role of the correlation potential.
AB  - The framework of ab initio density-functional theory (DFT) has been introduced as
      a way to provide a seamless connection between the Kohn-Sham (KS) formulation of
      DFT and wave-function based ab initio approaches [R. J. Bartlett, I. Grabowski,
      S. Hirata, and S. Ivanov, J. Chem. Phys. 122, 034104 (2005)]. Recently, an
      analysis of the impact of dynamical correlation effects on the density of the
      neon atom was presented [K. Jankowski, K. Nowakowski, I. Grabowski, and J.
      Wasilewski, J. Chem. Phys. 130, 164102 (2009)], contrasting the behaviour for a
      variety of standard density functionals with that of ab initio approaches based
      on second-order Moller-Plesset (MP2) and coupled cluster theories at the singles
      doubles (CCSD) and singles-doubles perturbative triples [CCSD(T)] levels. In the
      present work, we consider ab initio density functionals based on second-order
      many-body perturbation theory and coupled cluster perturbation theory in a
      similar manner, for a range of small atomic and molecular systems. For
      comparison, we also consider results obtained from MP2, CCSD, and CCSD(T)
      calculations. In addition to this density based analysis, we determine the KS
      correlation potentials corresponding to these densities and compare them with
      those obtained for a range of ab initio density functionals via the optimized
      effective potential method. The correlation energies, densities, and potentials
      calculated using ab initio DFT display a similar systematic behaviour to those
      derived from electronic densities calculated using ab initio wave function
      theories. In contrast, typical explicit density functionals for the correlation
      energy, such as VWN5 and LYP, do not show behaviour consistent with this picture
      of dynamical correlation, although they may provide some degree of correction for
      already erroneous explicitly density-dependent exchange-only functionals. The
      results presented here using orbital dependent ab initio density functionals show
      that they provide a treatment of exchange and correlation contributions within
      the KS framework that is more consistent with traditional ab initio wave function
      based methods.

PMID- 21950855
TI  - Producing translationally cold, ground-state CO molecules.
AB  - Carbon monoxide molecules in their electronic, vibrational, and rotational ground
      state are highly attractive for trapping experiments. The optical or ac electric
      traps that can be envisioned for these molecules will be very shallow, however,
      with depths in the sub-milliKelvin range. Here, we outline that the required
      samples of translationally cold CO (X(1)Sigma(+), v'' = 0, N'' = 0) molecules can
      be produced after Stark deceleration of a beam of laser-prepared metastable CO
      (a(3)Pi(1)) molecules followed by optical transfer of the metastable species to
      the ground state via perturbed levels in the A(1)Pi state. The optical transfer
      scheme is experimentally demonstrated and the radiative lifetimes and the
      electric dipole moments of the intermediate levels are determined.

PMID- 21950856
TI  - Valence anions of N-acetylproline in the gas phase: computational and anion
      photoelectron spectroscopic studies.
AB  - We report the photoelectron spectrum of anionic N-acetylproline, (N-AcPro)(-),
      measured with 3.49 eV photons. This spectrum, which consists of a band centered
      at an electron binding energy of 1.4 eV and a higher energy spectral tail,
      confirms that N-acetylproline forms a valence anion in the gas phase. The
      neutrals and anions of N-AcPro were also studied computationally at the B3LYP/6
      31++G(d,p) level. Based on the calculations, we conclude that the photoelectron
      spectrum is due to anions which originated from proton transfer induced by
      electron attachment to the pi* orbital localized at the acetyl group of N-AcPro.
      We also characterized the energetics of reaction paths leading to pyrrolidine
      ring opening in the anionic N-AcPro. These data suggest that electron induced
      decomposition of peptides/proteins comprising proline strongly depends on the
      presence of proton donors in the close vicinity to the proline residue.

PMID- 21950857
TI  - Efficient long-range collisional energy transfer between the E0(g)(+)(3P2) and
      D0(u)(+)(3P2) ion-pair states of I2, induced by H2O, observed using high
      resolution Fourier transform emission spectroscopy.
AB  - Using high-resolution Fourier transform emission techniques, we have resolved
      rotational structure in the D0(u)(+)((3)P(2)) -> X0(g)(+) emission following
      collisional transfer from the E0(g)(+)((3)P(2)) state in I(2). The P:R branch
      ratios in the E0(g)(+)((3)P(2)) -> D0(u)(+)((3)P(2)) transfer are found to vary
      enormously with v(E) and v(D). We show that the observed intensities are all
      consistent with the transfer being dominated by long-range, near-resonant
      collisions with residual H(2)O. Unequal P:R branch ratios in the
      E0(g)(+)((3)P(2)) -> A1(u) emission have been shown to result from mixing of the
      E0(g)(+)((3)P(2)) and beta1(g)((3)P(2)) states via Omega-uncoupling.

PMID- 21950858
TI  - Spectral characterization in a supersonic beam of neutral chlorophyll a
      evaporated from spinach leaves.
AB  - The observation of the light absorption of neutral biomolecules has been made
      possible by a method implemented for their preparation in the gas phase, in
      supersonically cooled molecular beams, based upon the work of Focsa et al. [C.
      Mihesan, M. Ziskind, B. Chazallon, E. Therssen, P. Desgroux, S. Gurlui, and C.
      Focsa, Appl. Surf. Sci. 253, 1090 (2006)]. The biomolecules diluted in frozen
      water solutions are entrained in the gas plume of evaporated ice generated by an
      infrared optical parametric oscillators (OPO) laser tuned close to its maximum of
      absorption, at ~3 MUm. The biomolecules are then picked up in the flux of a
      supersonic expansion of argon. The method was tested with indole dissolved in
      water. The excitation spectrum of indole was found cold and large clusters of
      indole with water were observed up to n = 75. Frozen spinach leaves were examined
      with the same method to observe the chlorophyll pigments. The Q(y) band of
      chlorophyll a has been observed in a pump probe experiment. The Q(y) bands of
      chlorophyll a is centred at 647 nm, shifted by 18 nm from its position in toluene
      solutions. The ionization threshold could also be determined as 6.1 +/- 0.05 eV.

PMID- 21950859
TI  - Resonant two-photon ionization spectroscopy of jet-cooled OsN: 520-418 nm.
AB  - The optical transitions of supersonically cooled OsN have been investigated in
      the range from 19,200 to 23,900 cm(-1) using resonant two-photon ionization
      spectroscopy. More than 20 vibronic bands were observed, 17 of which were
      rotationally resolved and analyzed. The ground state is confirmed to be
      (2)Delta(5/2), deriving from the 1sigma(2) 2sigma(2) 1pi(4) 1delta(3) 3sigma(2)
      electronic configuration. The X (2)Delta(5/2) ground state rotational constant
      for (192)Os(14)N was found to be B(0) = 0.491921(34) cm(-1), giving r(0) =
      1.62042(6) A (1sigma error limits). The observed bands were grouped into three
      band systems with Omega' = 7/2 and four with Omega' = 3/2, corresponding to the
      three (2)Phi(7/2) and four (2)Pi(3/2) states expected from the 1sigma(2)
      2sigma(2) 1pi(4) 1delta(3) 3sigma(1) 2pi(1) and 1sigma(2) 2sigma(2) 1pi(4)
      1delta(2) 3sigma(2) 2pi(1) electronic configurations. In addition, two
      interacting upper states with Omega' = 5/2 were observed, one of which is thought
      to correspond to a 1sigma(2) 2sigma(2) 1pi(3) 1delta(3) 3sigma(2) 2pi(1),
      (2)Delta(5/2) state. Spectroscopic constants are reported for all of the observed
      states, and comparisons to related molecules are made. The ionization energy of
      OsN is estimated as IE(OsN) = 8.80 +/- 0.06 eV.

PMID- 21950860
TI  - Consistent assignment of the vibrations of monosubstituted benzenes.
AB  - We investigate the consistency of the labeling and assignments of the vibrations
      of the monosubstituted benzenes in the electronic ground state. In doing so, we
      also identify some inconsistencies in the labeling of the benzene modes. We
      commence by investigating the behavior of the benzene vibrations as one hydrogen
      is replaced by an artificial atomic substituent of increasing mass via quantum
      chemical calculations; the wavenumber variations with mass give insight into the
      assignments. We also examine how well the monohalobenzene vibrations can be
      described in terms of the benzene ones: consistent with some recent studies, we
      conclude that this is futile in a significant number of cases. We then show that
      "isotopic wavenumbers" obtained by artificially changing the mass of the fluorine
      atom in fluorobenzene are in very good agreement with the wavenumbers obtained
      via explicit calculation for the relevant monohalobenzene (chlorobenzene,
      bromobenzene, and iodobenzene) vibrations. As a consequence, we propose that the
      vibrations of monofluorobenzene be used as the basis for labelling the
      vibrational assignments of monosubstituted benzenes. As well as the four
      monohalobenzenes, we also apply this approach to the vibrations of aniline,
      toluene, benzonitrile, phenylacetylene, phenylphosphine, and nitrobenzene. This
      has allowed a much more consistent picture of the vibrational assignments to be
      obtained across ten monosubstituted benzenes.

PMID- 21950861
TI  - Shattering dissociation in high-energy molecular collisions between nitrate
      esters.
AB  - We present ab initio molecular dynamics simulations of head-on collisions between
      ethyl nitrate molecules at collisional energies from 200 to 1200 kJ/mol. Above a
      threshold energy, an increasing fraction of the collisions led to rapid
      dissociation on impact--"shattering." The probability of the shattering
      dissociation was derived from the quasiclassical trajectories sampling the
      initial vibrational motion at T(vib) = 300 K. Even for the zero impact parameter
      and a fixed orientation considered, the observed dissociation probability
      exhibited a wide spread (much larger than kT(vib)) as a function of the collision
      energy. This is attributed to variations in the initial vibrational phase. We
      propose a closed-form expression for the energy-dependent dissociation
      probability that captures the dependence on the phase and use it to analyze the
      probability of the shattering dissociation of a larger nitrate ester,
      pentaerythritol tetranitrate.

PMID- 21950862
TI  - A quantum reaction dynamics study of the translational, vibrational, and
      rotational motion effects on the HD + H3+ reaction.
AB  - Time-dependent, quantum reaction dynamics wavepacket approach is employed to
      investigate the impacts of the translational, vibrational, and rotational motion
      on the HD+H(3)(+) -> H(2)D(+) + H(2) reaction using the Xie-Braams-Bowman
      potential energy surface [Z. Xie, B. J. Braams, and J. M. Bowman, J. Chem. Phys.
      122, 224307 (2005)]. We treat this five atom reaction with a seven-degree-of
      freedom model by fixing one Jacobi and one torsion angle related to H(3) (+) at
      the lowest saddle point geometry of the potential energy surface. The initial
      state selected reaction probabilities show that the rotational excitations of
      H(+)-H(2) greatly enhance the reactivity with the reaction probabilities
      increased double at high rotational states compared to the ground state. However,
      the vibrational excitations of H(3) (+) hinder the reactivity. The ground state
      reaction probability shows no reaction threshold for this exoergic reaction, and
      as the translational energy increases, the reaction probability decreases.
      Furthermore, reactive resonances and zero point energy play very important roles
      on the reaction dynamics. The obtained integral cross section has the character
      of an exoergic reaction without a threshold: it decreases with the translational
      energy increasing. The calculated thermal rate constants using this seven-degree
      of-freedom model are in agreement with a later experiment measurement.

PMID- 21950863
TI  - Nonadiabatic quantum dynamics of C(1D)+H2->CH+H: coupled-channel calculations
      including Renner-Teller and Coriolis terms.
AB  - The Renner-Teller (RT) coupled-channel dynamics for the C((1)D)+H(2)(X(1)Sigma(g)
      (+))->CH(X(2)Pi)+H((2)S) reaction has been investigated for the first time,
      considering the first two singlet states a(1)A' and b(1)A'' of CH(2) dissociating
      into the products and RT couplings, evaluated through the ab initio matrix
      elements of the electronic angular momentum. We have obtained initial-state
      resolved probabilities, cross sections and thermal rate constants via the real
      wavepacket method for both coupled electronic states. In contrast to the
      N((2)D)+H(2)(X(1)Sigma(g)(+)) system, RT effects tend to reduce probabilities,
      cross sections, and rate constants in the low energy range compared to Born
      Oppenheimer (BO) ones, due to the presence of a repulsive RT barrier in the
      effective potentials and to long-lived resonances. Furthermore, contrary to BO
      results, the rate constants have a positive temperature dependence in the 100-400
      K range. The two-state RT rate constant at 300 K, lower than the BO one, remains
      inside the error bars of the experimental value.

PMID- 21950864
TI  - Fragmentation of singly charged adenine induced by neutral fluorine beam impact
      at 3 keV.
AB  - The fragmentation scheme of singly charged adenine molecule (H(5)C(5)N(5)(+)) has
      been studied via neutral fluorine impact at 3 keV. By analyzing in correlation
      the kinetic energy loss of the scattered projectile F(-) produced in single
      charge transfer process and the mass of the charged fragments, the excitation
      energy distribution of the parent adenine molecular ions has been determined for
      each of the main dissociation channels. Several fragmentation pathways unrevealed
      in standard mass spectra or in appearance energy measurements are investigated.
      Regarding the well-known hydrogen cyanide (HCN) loss sequence, we demonstrate
      that although the loss of a HCN is the dominant decay channel for the parent
      H(5)C(5)N(5)(+) (m = 135), the decay of the first daughter ion H(4)C(4)N(4)(+) (m
      = 108) involves not only the HNC (m = 27) loss but also the symmetric breakdown
      into two dimers of HCN.

PMID- 21950865
TI  - Consistent treatment of coherent and incoherent energy transfer dynamics using a
      variational master equation.
AB  - We investigate the energy transfer dynamics in a donor-acceptor model by
      developing a time-local master equation technique based on a variational
      transformation of the underlying Hamiltonian. The variational transformation
      allows a minimisation of the Hamiltonian perturbation term dependent on the
      system parameters, and consequently results in a versatile master equation valid
      over a range of system-bath coupling strengths, temperatures, and environmental
      spectral densities. While our formalism reduces to the well-known Redfield,
      Forster and polaron forms in the appropriate limits, in general it is not
      equivalent to perturbing in either the system-environment or donor-acceptor
      coupling strengths, and hence can provide reliable results between these limits
      as well. Moreover, we show how to include the effects of both environmental
      correlations and non-equilibrium preparations within the formalism.

PMID- 21950866
TI  - Proton transport in a binary biomimetic solution revealed by molecular dynamics
      simulation.
AB  - We report the simulation results of the proton transport in a binary mixture of
      amphiphilic tetramethylurea (TMU) molecules and water. We identify different
      mechanisms that either facilitate or retard the proton transport. The efficiency
      of these mechanisms depends on the TMU concentration. The overall picture is more
      complicated than a recent suggestion that the presence of amphiphilic molecules
      suppresses the proton mobility by slowing down the reorientation of the
      surrounding water molecules. It has also been suggested that the hydronium ion
      induces local water orientational order, which results in an ordered region that
      has to move along with the proton potentially slowing down the proton transport
      as suggested by experiment. We find that water-wire like structures formed at low
      amphiphile concentrations facilitate proton transfer, and reduction of the
      hydrogen bond connectivity induced at high concentrations retards it.

PMID- 21950867
TI  - Formation and relaxation dynamics of iso-CH2Cl-I in cryogenic matrices.
AB  - Photolysis of chloroiodomethane (CH(2)ClI) in cryogenic matrices followed by
      recombination of the nascent radical pair produces an isomer (CH(2)Cl-I) that
      features a halogen-halogen (Cl-I) bond. Using ultrafast laser pulses, it is
      possible to follow the formation of this isomer by transient electronic
      absorption in low-temperature matrices of N(2), CH(4), and Ar. Frequency-domain
      measurements provide vibrational and electronic spectra, and electronic structure
      calculations give the structures of the isomers and the minimum energy path that
      connects them. The ultrafast experiments cleave the C-I bond with a 267-nm
      photolysis pulse and probe the formation of the isomer at wavelengths between 435
      nm and 510 nm. The longest wavelengths preferentially interrogate vibrationally
      excited molecules, and their transient absorption shows that the highly
      vibrationally excited isomer appears within 1 to 2 ps, depending on the matrix,
      likely reflecting the loss of 2000 cm(-1) or more of energy in a strong,
      inelastic collision of the fragments with the matrix. The subsequent relaxation
      of the vibrationally excited isomer occurs in 20 to 40 ps, a time that is
      comparable to those observed for halomethane molecules and their isomers in
      liquids and in supercritical CO(2). These observations suggest that the formation
      and initial relaxation of the isomer in dense media do not depend strongly on the
      identity of the surroundings.

PMID- 21950868
TI  - Higher order diffusion Monte Carlo propagators for linear rotors as diffusion on
      a sphere: development and application to O2@He(n).
AB  - Exploiting the theoretical treatment of particles diffusing on corrugated
      surfaces and the isomorphism between the "particle on a sphere" and a linear
      molecule rotation, a new diffusion kernel is introduced to increase the order of
      diffusion Monte Carlo (DMC) simulations involving linear rotors. Tests carried
      out on model systems indicate the superior performances of the new rotational
      diffusion kernel with respect to the simpler alternatives previously employed. In
      particular, it is evidenced a second order convergence toward exact results with
      respect to the time step of dynamical correlation functions, a fact that
      guarantees an identical order for the diffusion part of the DMC projector. The
      algorithmic advantages afforded by the latter are discussed, especially with
      respect to the "a posteriori" and "on the fly" extrapolation schemes. As a first
      application to the new algorithm, the structure and energetics of O(2)@He(n) (n =
      1-40) clusters have been studied. This was done to investigate the possible cause
      of the quenching of the reaction between O(2) and Mg witnessed upon increasing
      the size of superfluid He droplets used as a solvent. With the simulations on
      O(2) indicating a strong localization in the cluster core, the behaviour as a
      function of n is ascribed to the extremely fluxional comportment of Mg@He(n),
      which dwells far from the droplet center, albeit being solvated, when n is large.

PMID- 21950869
TI  - Influence of temperature on thymine-to-solvent vibrational energy transfer.
AB  - At the instant following the non-radiative deactivation of its pipi* electronic
      state, the vibrational modes of thymine possess a highly non-equilibrium
      distribution of excitation quanta (i.e., >4 eV in excess energy). Equilibrium is
      re-established through rapid (5 ps) vibrational energy transfer to the
      surrounding solvent. The mechanisms behind such vibrational cooling (VC)
      processes are examined here using femtosecond transient grating and two
      dimensional photon echo spectroscopies conducted at 100 K and 300 K in a mixture
      of methanol and water. Remarkably, we find that this variation in temperature has
      essentially no impact on the VC kinetics. Together the experiments and a
      theoretical model suggest three possible mechanisms consistent with this
      behavior: (i) vibrational energy transfer from the solute to solvent initiates
      (directly) in intramolecular modes of the solute with frequencies >300 cm(-1);
      (ii) the relaxation induced increase in the temperature of the environment
      reduces the sensitivity of VC to the temperature of the equilibrium system; (iii)
      the time scale of solvent motion approaches 0.1 ps even at 100 K. Mechanism (i)
      deserves strong consideration because it is consistent with the conclusions drawn
      in earlier studies of isotope effects on VC in hydrogen bonding solvents. Our
      model calculations suggest that mechanism (ii) also plays a significant role
      under the present experimental conditions. Mechanism (iii) is ruled out on the
      basis of long-lived correlations evident in the photon echo line shapes at 100 K.
      These insights into photoinduced relaxation processes in thymine are made
      possible by our recent extension of interferometric transient grating and photon
      echo spectroscopies to the mid UV spectral region.

PMID- 21950870
TI  - Isotopic effect on the vibrational lifetime of the carbon-deuterium stretch
      excitation on graphene.
AB  - The relaxation of vibrational energy in the H and D stretch modes has been
      studied on the graphene surface using ab initio calculations. The dissipation of
      the vibrational energy stored in the stretching modes proceeds through vibration
      phonon coupling, while the dissipation through electronic excitations makes only
      minor contributions. Recently, we reported the fast relaxation of the H stretch
      energy on graphene [S. Sakong and P. Kratzer, J. Chem. Phys. 133, 054505 (2010)].
      Interestingly, we predict the lifetime of the D stretch to be markedly longer
      compared to the relaxation of the H stretch. This is unexpected since the
      vibrational amplitudes at carbon atoms in the joint C-D vibrational modes are
      larger than in the joint C-H modes, due to the mass ratio m(D)/m(C) > m(H)/m(C).
      However, the vibrational relaxation rate for the D stretch is smaller than for
      the H stretch, because the energy is dissipated to an acoustic phonon of graphene
      in the case of C-D rather than an optical phonon as is the case in C-H, and
      hence, the corresponding phonon density of states is lower in the C-D case. To
      rationalize our findings, we propose a general scheme for estimating vibrational
      lifetimes of adsorbates based on four factors: the density of states of the
      phonons that mediates the transitions, the vibration-phonon coupling strength,
      the anharmonic coupling between local modes, and the number of quanta involved in
      the transitions. Mainly the first two of these factors are responsible for the
      differences in the lifetimes of the C-H and C-D stretches. The possible role of
      the other factors is illustrated in the context of vibrational lifetimes in other
      recently studied systems.

PMID- 21950871
TI  - First-principles calculations of 17O nuclear magnetic resonance chemical
      shielding in Pb(Zr(1/2)Ti(1/2))O3 and Pb(Mg(1/3)Nb(2/3))O3: linear dependence on
      transition-metal/oxygen bond lengths.
AB  - First-principles density functional theory oxygen chemical shift tensors were
      calculated for A(B,B')O(3) perovskite alloys Pb(Zr(1/2)Ti(1/2))O(3) (PZT) and
      Pb(Mg(1/3)Nb(2/3))O(3) (PMN). Quantum chemistry methods for embedded clusters and
      the gauge including projector augmented waves (GIPAW) method [C. J. Pickard and
      F. Mauri, Phys. Rev. B 63, 245101 (2001)] for periodic boundary conditions were
      used. Results from both methods are in good agreement for PZT and prototypical
      perovskites. PMN results were obtained using only GIPAW. Both isotropic
      delta(iso) and axial delta(ax) chemical shifts were found to vary approximately
      linearly as a function of the nearest-distance transition-metal/oxygen bond
      length, r(s). Using these results, we argue against Ti clustering in PZT, as
      conjectured from recent (17)O NMR magic-angle-spinning measurements. Our findings
      indicate that (17)O NMR measurements, coupled with first-principles calculations,
      can be an important probe of local structure in complex perovskite solid
      solutions.

PMID- 21950872
TI  - Chiral hide-and-seek: retention of enantiomorphism in laser-induced nucleation of
      molten sodium chlorate.
AB  - We report the observation of non-photochemical laser-induced nucleation (NPLIN)
      of sodium chlorate from its melt using nanosecond pulses of light at 1064 nm. The
      fraction of samples that nucleate is shown to depend linearly on the peak power
      density of the laser pulses. Remarkably, we observe that most samples are
      nucleated by the laser back into the enantiomorph (dextrorotatory or
      levorotatory) of the solid prior to melting. We do not observe a significant
      dependence on polarization of the light, and we put forward symmetry arguments
      that rule out an optical Kerr effect mechanism. Our observations of retention of
      chirality can be explained by decomposition of small amounts of the sodium
      chlorate to form sodium chloride, which provide cavities for retention of
      clusters of sodium chlorate even 18  degrees C above the melting point. These
      clusters remain sub-critical on cooling, but can be activated by NPLIN via an
      isotropic polarizability mechanism. We have developed a heterogeneous model of
      NPLIN in cavities, which reproduces the experimental data using simple physical
      data available for sodium chlorate.

PMID- 21950873
TI  - Decoupling charge transport from the structural dynamics in room temperature
      ionic liquids.
AB  - Light scattering and dielectric spectroscopy measurements were performed on the
      room temperature ionic liquid (RTIL) [C4mim][NTf2] in a broad temperature and
      frequency range. Ionic conductivity was used to estimate self-diffusion of ions,
      while light scattering was used to study structural relaxation. We demonstrate
      that the ionic diffusion decouples from the structural relaxation process as the
      temperature of the sample decreases toward T(g). The strength of the decoupling
      appears to be significantly lower than that expected for a supercooled liquid of
      similar fragility. The structural relaxation process in the RTIL follows well the
      high-temperature mode coupling theory (MCT) scenario. Using the MCT analysis we
      estimated the dynamic crossover temperature in [C4mim][NTf2] to be T(c) ~ 225 +/-
      5 K. However, our analysis reveals no sign of the dynamic crossover in the ionic
      diffusion process.

PMID- 21950874
TI  - Hydrogen bonded structure and dynamics of liquid-vapor interface of water-ammonia
      mixture: an ab initio molecular dynamics study.
AB  - We have carried out ab initio molecular dynamics simulations of a liquid-vapor
      interfacial system consisting of a mixture of water and ammonia molecules. We
      have made a detailed analysis of the structural and dynamical properties of the
      bulk and interfacial regions of the mixture. Among structural properties, we have
      looked at the inhomogeneous density profiles of water and ammonia molecules,
      hydrogen bond distributions, orientational profiles, and also vibrational
      frequency distributions of bulk and interfacial molecules. It is found that the
      interfacial molecules show preference for specific orientations so as to form
      water-ammonia hydrogen bonds at the interface with ammonia as the acceptor. The
      structure of the system is also investigated in terms of inter-atomic voids
      present in the system. Among the dynamical properties, we have calculated the
      diffusion, orientational relaxation, hydrogen bond dynamics, and vibrational
      spectral diffusion in bulk and interfacial regions. It is found that the
      diffusion and orientation relaxation of the interfacial molecules are faster than
      those of the bulk. However, the hydrogen bond lifetimes are longer at the
      interface which can be correlated with the time scales found from the decay of
      frequency time correlations.

PMID- 21950875
TI  - Infrared spectroscopy of endohedral HD and D2 in C60.
AB  - We report on the dynamics of two hydrogen isotopomers, D(2) and HD, trapped in
      the molecular cages of a fullerene C(60) molecule. We measured the infrared
      spectra and analyzed them using a spherical potential for a vibrating rotor. The
      potential, vibration-rotation Hamiltonian, and dipole moment parameters are
      compared with previously studied H(2)@C(60) parameters [M. Ge, U. Nagel, D.
      Huvonen, T. Room, S. Mamone, M. H. Levitt, M. Carravetta, Y. Murata, K. Komatsu,
      J. Y.-C. Chen, and N. J. Turro, J. Chem. Phys. 134, 054507 (2011)]. The isotropic
      part of the potential is similar for all three isotopomers. In HD@C(60), we
      observe mixing of the rotational states and an interference effect of the dipole
      moment terms due to the displacement of the HD rotation center from the fullerene
      cage center.

PMID- 21950876
TI  - Geometrical structure and spin order of Gd13 cluster.
AB  - The spin-polarized generalized gradient approximation to the density-functional
      theory has been used to determine the lowest energy structure, electronic
      structure, and magnetic property of Gd(13) cluster. Our results show that the
      ionic bonding is combined with the covalent characteristics in stabilizing the Gd
      cluster. The ferrimagnetic icosahedron is found to be the lowest energy
      configuration, in which the centered Gd atom couples antiferromagnetically with
      the rest Gd atoms surrounding it. No spin non-collinear evidence has been
      detected in our calculations. It is identified that the local magnetic moments of
      Gd atom are about 8 MU(B) regardless of geometrical structure. Finally, the
      comprehensive electronic structure analyses show that the indirect long-range
      magnetic coupling between the polarized 4f is mediated by the polarization of 5d,
      6s, and 6p conduction electrons, which is the typical Ruderman-Kittel-Kasuya
      Yosida interactions.

PMID- 21950877
TI  - The dissociative chemisorption of methane on Ni(100): reaction path description
      of mode-selective chemistry.
AB  - We derive a model for the dissociative chemisorption of methane on a Ni(100)
      surface, based on the reaction path Hamiltonian, that includes all 15 molecular
      degrees of freedom within the harmonic approximation. The total wavefunction is
      expanded in the adiabatic vibrational states of the molecule, and close-coupled
      equations are derived for wave packets propagating on vibrationally adiabatic
      potential energy surfaces, with non-adiabatic couplings linking these states to
      each other. Vibrational excitation of an incident molecule is shown to
      significantly enhance the reactivity, if the molecule can undergo transitions to
      states of lower vibrational energy, with the excess energy converted into motion
      along the reaction path. Sudden models are used to average over surface impact
      site and lattice vibrations. Computed dissociative sticking probabilities are in
      good agreement with experiment, with respect to both magnitude and variation with
      energy. The nu(1) vibration is shown to have the largest efficacy for promoting
      reaction, due to its strong non-adiabatic coupling to the ground state, and a
      significant softening of the vibration at the transition state. Most of the
      reactivity at 475 K is shown to result from thermally assisted over-the-barrier
      processes, and not tunneling.

PMID- 21950878
TI  - Complex orientational ordering of C60 molecules on Au(111).
AB  - The orientation and adsorption site for C(60) molecules on Au(111) has been
      studied using low temperature scanning tunneling microscopy. A complex
      orientational ordering has been observed for molecules inside the "in-phase" (R0
      degrees ) domain. A 7-molecule cluster consisting a central molecule sitting atop
      of a gold atom and 6 tilted surrounding molecules is identified as the structural
      motif. The 2?3 * 2?3-R30 degrees  phase consists of molecules bonding to a gold
      atomic vacancies with a preferred azimuthal orientation. The quasi-periodic R14
      degrees  phase is composed of groups of similarly oriented molecules with the
      groups organized into a 4?3 * 4?3-R30 degrees  like super-lattice unit cell.

PMID- 21950879
TI  - A single centre water splitting dye complex adsorbed on rutile TiO2(110):
      photoemission, x-ray absorption, and optical spectroscopy.
AB  - A single centre water splitting dye complex (aqua(2,2'-bipyridyl-4,4'
      dicarboxylic acid)-(2,2':6',6''-terpyridine)Ruthenium(II)), along with a related
      complex ((2,2'-bipyridyl-4,4'-dicarboxylic acid)-(2,2':6',6''
      terpyridine)chloride Ruthenium(II)), has been investigated using photoemission
      and compared to molecules with similar structures. Dye molecules were deposited
      in situ using ultra-high vacuum electrospray deposition, which allows for the
      deposition of thermally labile molecules, such as these dye molecules. Adsorption
      of the dye molecules on the rutile TiO(2)(110) surface has been studied using
      core-level and valence photoemission. Core-level photoemission spectra reveal
      that each complex bonds to the surface via deprotonation of its carboxylic acid
      groups. A consideration of the energy level alignments reveals that both
      complexes are capable of charge transfer from the adsorbed molecules to the
      conduction band of the rutile TiO(2) substrate.

PMID- 21950880
TI  - Anomalous diffusion governed by a fractional diffusion equation and the
      electrical response of an electrolytic cell.
AB  - The electrical response of an electrolytic cell in which the diffusion of mobile
      ions in the bulk is governed by a fractional diffusion equation of distributed
      order is analyzed. The boundary conditions at the electrodes limiting the sample
      are described by an integro-differential equation governing the kinetic at the
      interface. The analysis is carried out by supposing that the positive and
      negative ions have the same mobility and that the electric potential profile
      across the sample satisfies the Poisson's equation. The results cover a rich
      variety of scenarios, including the ones connected to anomalous diffusion.

PMID- 21950881
TI  - Structure of solvent-free grafted nanoparticles: molecular dynamics and density
      functional theory.
AB  - The structure of solvent-free oligomer-grafted nanoparticles has been
      investigated using molecular dynamics simulations and density-functional theory.
      At low temperatures and moderate to high oligomer lengths, the qualitative
      features of the core particle pair probability, structure factor, and the
      oligomer brush configuration obtained from the simulations can be explained by a
      density-functional theory that incorporates the configurational entropy of the
      space-filling oligomers. In particular, the structure factor at small wave
      numbers attains a value much smaller than the corresponding hard-sphere
      suspension, the first peak of the pair distribution function is enhanced due to
      entropic attractions among the particles, and the oligomer brush expands with
      decreasing particle volume fraction to fill the interstitial space. At higher
      temperatures, the simulations reveal effects that differ from the theory and are
      likely caused by steric repulsions of the expanded corona chains.

PMID- 21950882
TI  - Markov chain modeling of polymer translocation through pores.
AB  - We solve the Chapman-Kolmogorov equation and study the exact splitting
      probabilities of the general stochastic process which describes polymer
      translocation through membrane pores within the broad class of Markov chains.
      Transition probabilities, which satisfy a specific balance constraint, provide a
      refinement of the Chuang-Kantor-Kardar relaxation picture of translocation,
      allowing us to investigate finite size effects in the evaluation of dynamical
      scaling exponents. We find that (i) previous Langevin simulation results can be
      recovered only if corrections to the polymer mobility exponent are taken into
      account and (ii) the dynamical scaling exponents have a slow approach to their
      predicted asymptotic values as the polymer's length increases. We also address,
      along with strong support from additional numerical simulations, a critical
      discussion which points in a clear way the viability of the Markov chain approach
      put forward in this work.

PMID- 21950883
TI  - Thermoreversible gelation of isotactic-rich poly(N-isopropylacrylamide) in water.
AB  - We report the experimentally determined phase diagram for an aqueous solution of
      isotactic-rich poly(N-isopropylacrylamide) (PNiPAM) composed of the sol-gel
      transition curve and the cloud-point curve. The meso diad content of isotactic
      rich PNiPAM is 64%, and it is soluble in water at low temperatures, but undergoes
      a sol-to-gel transition with increasing temperature in the investigated
      concentration range of 1.8 wt. %-6.0 wt. %. With a further increase in
      temperature, the system becomes turbid. The gel formation and clouding behavior
      are thermally reversible. This is the first observation of thermoreversible
      gelation under the cloud-point temperature for an aqueous solution of PNiPAM. On
      the basis of the determined phase diagram, we carried out light scattering
      experiments to characterize the sol-gel transition behavior as a function of
      temperature.

PMID- 21950884
TI  - Monte-Carlo simulation of ternary blends of block copolymers and homopolymers.
AB  - We perform a theoretically informed coarse grain Monte-Carlo simulation in the
      nPT-ensemble and the Gibbs ensemble on symmetric ternary mixtures of AB-diblock
      copolymers with the corresponding homopolymers. We study the lamellar period by
      varying the length and amount of homopolymers. The homopolymer distribution
      within the lamellar morphology is determined as is the maximum amount of
      homopolymer within the lamellae. Gibbs ensemble simulations are used to locate
      the three-phase coexistence between two homopolymer-rich phases and a lamellar
      phase.

PMID- 21950885
TI  - Thermodynamics of twisted DNA with solvent interaction.
AB  - The imaginary time path integral formalism is applied to a nonlinear Hamiltonian
      for a short fragment of heterogeneous DNA with a stabilizing solvent interaction
      term. Torsional effects are modeled by a twist angle between neighboring base
      pairs stacked along the molecule backbone. The base pair displacements are
      described by an ensemble of temperature dependent paths thus incorporating those
      fluctuational effects which shape the multisteps thermal denaturation. By summing
      over ~10(7)-10(8) base pair paths, a large number of double helix configurations
      is taken into account consistently with the physical requirements of the model
      potential. The partition function is computed as a function of the twist. It is
      found that the equilibrium twist angle, peculiar of B-DNA at room temperature,
      yields the stablest helicoidal geometry against thermal disruption of the base
      pair hydrogen bonds. This result is corroborated by the computation of
      thermodynamical properties such as fractions of open base pairs and specific
      heat.

PMID- 21950886
TI  - Note: Second virial coefficient of the water-hydrogen complex from an explicitly
      correlated potential energy surface.

PMID- 21950887
TI  - Note: Single-ultraviolet-photon dissociation dynamics of CS2(+)(X2Pi(g)) in 227
      243 nm revealed by time-sliced velocity map imaging.

PMID- 21950888
TI  - Comment on "Isotope effects in liquid water by infrared spectroscopy. IV. No free
      OH groups in liquid water" [J. Chem. Phys. 133, 164509 (2010)].

PMID- 21950894
TI  - In silico prediction of the mechanobiological response of arterial tissue:
      application to angioplasty and stenting.
AB  - One way to restore physiological blood flow to occluded arteries involves the
      deformation of plaque using an intravascular balloon and preventing elastic
      recoil using a stent. Angioplasty and stent implantation cause unphysiological
      loading of the arterial tissue, which may lead to tissue in-growth and
      reblockage; termed "restenosis." In this paper, a computational methodology for
      predicting the time-course of restenosis is presented. Stress-induced damage,
      computed using a remaining life approach, stimulates inflammation (production of
      matrix degrading factors and growth stimuli). This, in turn, induces a change in
      smooth muscle cell phenotype from contractile (as exists in the quiescent tissue)
      to synthetic (as exists in the growing tissue). In this paper, smooth muscle cell
      activity (migration, proliferation, and differentiation) is simulated in a
      lattice using a stochastic approach to model individual cell activity. The
      inflammation equations are examined under simplified loading cases. The
      mechanobiological parameters of the model were estimated by calibrating the model
      response to the results of a balloon angioplasty study in humans. The simulation
      method was then used to simulate restenosis in a two dimensional model of a
      stented artery. Cell activity predictions were similar to those observed during
      neointimal hyperplasia, culminating in the growth of restenosis. Similar to
      experiment, the amount of neointima produced increased with the degree of
      expansion of the stent, and this relationship was found to be highly dependant on
      the prescribed inflammatory response. It was found that the duration of
      inflammation affected the amount of restenosis produced, and that this effect was
      most pronounced with large stent expansions. In conclusion, the paper shows that
      the arterial tissue response to mechanical stimulation can be predicted using a
      stochastic cell modeling approach, and that the simulation captures features of
      restenosis development observed with real stents. The modeling approach is
      proposed for application in three dimensional models of cardiovascular stenting
      procedures.

PMID- 21950895
TI  - A new PMHS model for lumbar spine injuries during vertical acceleration.
AB  - Ejection from military aircraft exerts substantial loads on the lumbar spine.
      Fractures remain common, although the overall survivability of the event has
      considerably increased over recent decades. The present study was performed to
      develop and validate a biomechanically accurate experimental model for the high
      vertical acceleration loading to the lumbar spine that occurs during the catapult
      phase of aircraft ejection. The model consisted of a vertical drop tower with two
      horizontal platforms attached to a monorail using low friction linear bearings. A
      total of four human cadaveric spine specimens (T12-L5) were tested. Each lumbar
      column was attached to the lower platform through a load cell. Weights were added
      to the upper platform to match the thorax, head-neck, and upper extremity mass of
      a 50th percentile male. Both platforms were raised to the drop height and
      released in unison. Deceleration characteristics of the lower platform were
      modulated by foam at the bottom of the drop tower. The upper platform applied
      compressive inertial loads to the top of the specimen during deceleration. All
      specimens demonstrated complex bending during ejection simulations, with the
      pattern dependent upon the anterior-posterior location of load application. The
      model demonstrated adequate inter-specimen kinematic repeatability on a spinal
      level-by-level basis under different subfailure loading scenarios. One specimen
      was then exposed to additional tests of increasing acceleration to induce
      identifiable injury and validate the model as an injury-producing system.
      Multiple noncontiguous vertebral fractures were obtained at an acceleration of 21
      g with 488 g/s rate of onset. This clinically relevant trauma consisted of burst
      fracture at L1 and wedge fracture at L4. Compression of the vertebral body
      approached 60% during the failure test, with -6,106 N axial force and 168 Nm
      flexion moment. Future applications of this model include developing a better
      understanding of the vertebral injury mechanism during pilot ejection and
      developing tolerance limits for injuries sustained under a variety of different
      vertical acceleration scenarios.

PMID- 21950896
TI  - Comparative study of viscoelastic arterial wall models in nonlinear one
      dimensional finite element simulations of blood flow.
AB  - It is well known that blood vessels exhibit viscoelastic properties, which are
      modeled in the literature with different mathematical forms and experimental
      bases. The wide range of existing viscoelastic wall models may produce
      significantly different blood flow, pressure, and vessel deformation solutions in
      cardiovascular simulations. In this paper, we present a novel comparative study
      of two different viscoelastic wall models in nonlinear one-dimensional (1D)
      simulations of blood flow. The viscoelastic models are from papers by Holenstein
      et al. in 1980 (model V1) and Valdez-Jasso et al. in 2009 (model V2). The static
      elastic or zero-frequency responses of both models are chosen to be identical.
      The nonlinear 1D blood flow equations incorporating wall viscoelasticity are
      solved using a space-time finite element method and the implementation is
      verified with the Method of Manufactured Solutions. Simulation results using
      models V1, V2 and the common static elastic model are compared in three
      application examples: (i) wave propagation study in an idealized vessel with
      reflection-free outflow boundary condition; (ii) carotid artery model with
      nonperiodic boundary conditions; and (iii) subject-specific abdominal aorta model
      under rest and simulated lower limb exercise conditions. In the wave propagation
      study the damping and wave speed were largest for model V2 and lowest for the
      elastic model. In the carotid and abdominal aorta studies the most significant
      differences between wall models were observed in the hysteresis (pressure-area)
      loops, which were larger for V2 than V1, indicating that V2 is a more dissipative
      model. The cross-sectional area oscillations over the cardiac cycle were smaller
      for the viscoelastic models compared to the elastic model. In the abdominal aorta
      study, differences between constitutive models were more pronounced under
      exercise conditions than at rest. Inlet pressure pulse for model V1 was larger
      than the pulse for V2 and the elastic model in the exercise case. In this paper,
      we have successfully implemented and verified two viscoelastic wall models in a
      nonlinear 1D finite element blood flow solver and analyzed differences between
      these models in various idealized and physiological simulations, including
      exercise. The computational model of blood flow presented here can be utilized in
      further studies of the cardiovascular system incorporating viscoelastic wall
      properties.

PMID- 21950897
TI  - A nonlinear biphasic fiber-reinforced porohyperviscoelastic model of articular
      cartilage incorporating fiber reorientation and dispersion.
AB  - A nonlinear biphasic fiber-reinforced porohyperviscoelastic (BFPHVE) model of
      articular cartilage incorporating fiber reorientation effects during applied load
      was used to predict the response of ovine articular cartilage at relatively high
      strains (20%). The constitutive material parameters were determined using a
      coupled finite element-optimization algorithm that utilized stress relaxation
      indentation tests at relatively high strains. The proposed model incorporates the
      strain-hardening, tension-compression, permeability, and finite deformation
      nonlinearities that inherently exist in cartilage, and accounts for effects
      associated with fiber dispersion and reorientation and intrinsic viscoelasticity
      at relatively high strains. A new optimization cost function was used to overcome
      problems associated with large peak-to-peak differences between the predicted
      finite element and experimental loads that were due to the large strain levels
      utilized in the experiments. The optimized material parameters were found to be
      insensitive to the initial guesses. Using experimental data from the literature,
      the model was also able to predict both the lateral displacement and reaction
      force in unconfined compression, and the reaction force in an indentation test
      with a single set of material parameters. Finally, it was demonstrated that
      neglecting the effects of fiber reorientation and dispersion resulted in poorer
      agreement with experiments than when they were considered. There was an
      indication that the proposed BFPHVE model, which includes the intrinsic
      viscoelasticity of the nonfibrillar matrix (proteoglycan), might be used to model
      the behavior of cartilage up to relatively high strains (20%). The maximum
      percentage error between the indentation force predicted by the FE model using
      the optimized material parameters and that measured experimentally was 3%.

PMID- 21950898
TI  - Finite element implementation of mechanochemical phenomena in neutral deformable
      porous media under finite deformation.
AB  - Biological soft tissues and cells may be subjected to mechanical as well as
      chemical (osmotic) loading under their natural physiological environment or
      various experimental conditions. The interaction of mechanical and chemical
      effects may be very significant under some of these conditions, yet the highly
      nonlinear nature of the set of governing equations describing these mechanisms
      poses a challenge for the modeling of such phenomena. This study formulated and
      implemented a finite element algorithm for analyzing mechanochemical events in
      neutral deformable porous media under finite deformation. The algorithm employed
      the framework of mixture theory to model the porous permeable solid matrix and
      interstitial fluid, where the fluid consists of a mixture of solvent and solute.
      A special emphasis was placed on solute-solid matrix interactions, such as solute
      exclusion from a fraction of the matrix pore space (solubility) and frictional
      momentum exchange that produces solute hindrance and pumping under certain
      dynamic loading conditions. The finite element formulation implemented full
      coupling of mechanical and chemical effects, providing a framework where material
      properties and response functions may depend on solid matrix strain as well as
      solute concentration. The implementation was validated using selected canonical
      problems for which analytical or alternative numerical solutions exist. This
      finite element code includes a number of unique features that enhance the
      modeling of mechanochemical phenomena in biological tissues. The code is
      available in the public domain, open source finite element program FEBio
      (http://mrl.sci.utah.edu/software).

PMID- 21950899
TI  - Advances in finite element simulations of elastosonography for breast lesion
      detection.
AB  - Among the available tools for the early diagnosis of breast cancer, the
      elastographic technique based on ultrasounds has many advantages such as the
      noninvasive measure, the absence of ionizing effects, the high tolerability by
      patients, and the wide diffusion of the ecographic machines. However this
      diagnostic procedure is strongly affected by many subjective factors and is
      considered not reliable enough even to reduce the number of biopsies used to
      identify the nature of lesions. Therefore in the literature experimental and
      numerical simulations on physical and virtual phantoms are presented to test and
      validate procedures and algorithms and to interpret elastosonographic results. In
      this work, first a description of the elastographic technique and a review of the
      principal finite element (FE) models are provided and second diagnostic indexes
      employed to assess the nature of a lump mass are presented. As advances in FE
      simulations of elastosonography, axisymmetric phantom, and anthropomorphic models
      are described, which, with respect to the literature, include some features of
      breast mechanics. In particular deterministic analyses were used to compare the
      various details of virtual elastograms and also to investigate diagnostic indexes
      with respect to the regions where strains were considered. In order to improve
      the reliability of the elastosonographic procedure, univariate and multivariate
      sensitivity analyses, based on a probabilistic FE approach, were also performed
      to identify the parameters that mostly influence the deformation contrast between
      healthy and cancerous tissues. Moreover, synthetic indicators of the strain
      field, such as the strain contrast coefficient, were evaluated in different
      regions of interest in order to identify the most suitable for lesion type
      assessment. The deterministic analyses show that the malignant lesion is
      characterized by a uniform strain inside the inclusion due to the firmly bonding
      condition, while in the benign inclusion (loosely bonded) a strain gradient is
      observed independently from the elastic modulus contrast. The multivariate
      analyses reveal that the strain contrast depends linearly on the relative
      stiffness between the lesion and the healthy tissue and not linearly on the
      interface friction coefficient. The anthropomorphic model shows other interesting
      features, such as the layer or curvature effects, which introduce difficulties in
      selecting a reference region for strain assessment. The results show that a
      simple axisymmetric model with linear elastic material properties can be suitable
      to simulate the elastosonographic procedure although the breast curvature and
      layer distinction play a significant role in the strain assessment.

PMID- 21950900
TI  - Cell-to-cell variability in deformations across compressed myoblasts.
AB  - Many biological consequences of external mechanical loads applied to cells depend
      on localized cell deformations rather than on average whole-cell-body
      deformations. Such localized intracellular deformations are likely to depend, in
      turn, on the individual geometrical features of each cell, e.g., the local
      surface curvatures or the size of the nucleus, which always vary from one cell to
      another, even within the same culture. Our goal here was to characterize cell-to
      cell variabilities in magnitudes and distribution patterns of localized tensile
      strains that develop in the plasma membrane (PM) and nuclear surface area (NSA)
      of compressed myoblasts, in order to identify resemblance or differences in
      mechanical performances across the cells. For this purpose, we utilized our
      previously developed confocal microscopy-based three-dimensional cell-specific
      finite element modeling methodology. Five different C2C12 undifferentiated cells
      belonging to the same culture were scanned confocally and modeled, and were then
      subjected to compression in the simulation setting. We calculated the average and
      peak tensile strains in the PM and NSA, the percentage of PM area subjected to
      tensile strains above certain thresholds and the coefficient of variation (COV)
      in average and peak strains. We found considerable COV values in tensile strains
      developing at the PM and NSA (up to ~35%) but small external compressive
      deformations induced greater variabilities in intracellular strains across cells
      compared to large deformations. Interestingly, the external deformations needed
      to cause localized PM or NSA strains exceeding each threshold were very close
      across the different cells. Better understanding of variabilities in mechanical
      performances of cells-either of the same type or of different types-is important
      for interpreting experimental data in any experiments involving delivery of
      mechanical loads to cells.

PMID- 21950901
TI  - Design optimization of scaffold microstructures using wall shear stress criterion
      towards regulated flow-induced erosion.
AB  - Tissue scaffolds aim to provide a cell-friendly biomechanical environment for
      facilitating cell growth. Existing studies have shown significant demands for
      generating a certain level of wall shear stress (WSS) on scaffold microstructural
      surfaces for promoting cellular response and attachment efficacy. Recently, its
      role in shear-induced erosion of polymer scaffold has also drawn increasing
      attention. This paper proposes a bi-directional evolutionary structural
      optimization (BESO) approach for design of scaffold microstructure in terms of
      the WSS uniformity criterion, by downgrading highly-stressed solid elements into
      fluidic elements and/or upgrading lowly-stressed fluidic elements into solid
      elements. In addition to this, a computational model is presented to simulate
      shear-induced erosion process. The effective stiffness and permeability of
      initial and optimized scaffold microstructures are characterized by the finite
      element based homogenization technique to quantify the variations of mechanical
      properties of scaffold during erosion. The illustrative examples show that a
      uniform WSS is achieved within the optimized scaffold microstructures, and their
      architectural and biomechanical features are maintained for a longer lifetime
      during shear-induced erosion process. This study provides a mathematical means to
      the design optimization of cellular biomaterials in terms of the WSS criterion
      towards controllable shear-induced erosion.

PMID- 21950902
TI  - Biomechanical assessment of a PEEK rod system for semi-rigid fixation of lumbar
      fusion constructs.
AB  - The concept of semi-rigid fixation (SRF) has driven the development of spinal
      implants that utilize nonmetallic materials and novel rod geometries in an effort
      to promote fusion via a balance of stability, intra- and inter-level load
      sharing, and durability. The purpose of this study was to characterize the
      mechanical and biomechanical properties of a pedicle screw-based
      polyetheretherketone (PEEK) SRF system for the lumbar spine to compare its
      kinematic, structural, and durability performance profile against that of
      traditional lumbar fusion systems. Performance of the SRF system was
      characterized using a validated spectrum of experimental, computational, and in
      vitro testing. Finite element models were first used to optimize the size and
      shape of the polymeric rods and bound their performance parameters. Subsequently,
      benchtop tests determined the static and dynamic performance threshold of PEEK
      rods in relevant loading modes (flexion-extension (F/E), axial rotation (AR), and
      lateral bending (LB)). Numerical analyses evaluated the amount of anteroposterior
      column load sharing provided by both metallic and PEEK rods. Finally, a cadaveric
      spine simulator was used to determine the level of stability that PEEK rods
      provide. Under physiological loading conditions, a 6.35 mm nominal diameter oval
      PEEK rod construct unloads the bone-screw interface and increases anterior column
      load (approx. 75% anterior, 25% posterior) when compared to titanium (Ti) rod
      constructs. The PEEK construct's stiffness demonstrated a value lower than that
      of all the metallic rod systems, regardless of diameter or metallic composition
      (78% < 5.5 mm Ti; 66% < 4.5 mm Ti; 38% < 3.6 mm Ti). The endurance limit of the
      PEEK construct was comparable to that of clinically successful metallic rod
      systems (135N at 5 * 10(6) cycles). Compared to the intact state, cadaveric
      spines implanted with PEEK constructs demonstrated a significant reduction of
      range of motion in all three loading directions (> 80% reduction in F/E, p <
      0.001; > 70% reduction in LB, p < 0.001; > 54% reduction in AR, p < 0.001). There
      was no statistically significant difference in the stability provided by the PEEK
      rods and titanium rods in any mode (p = 0.769 for F/E; p = 0.085 for LB; p =
      0.633 for AR). The CD HORIZON((r)) LEGACY(TM) PEEK Rod System provided
      intervertebral stability comparable to currently marketed titanium lumbar fusion
      constructs. PEEK rods also more closely approximated the physiologic
      anteroposterior column load sharing compared to results with titanium rods. The
      durability, stability, strength, and biomechanical profile of PEEK rods were
      demonstrated and the potential advantages of SRF were highlighted.

PMID- 21950903
TI  - An argument for the use of multiple segment stents in curved arteries.
AB  - Stenting of curved arteries is generally perceived to be more challenging than
      straight vessels. Conceptually implanting multiple shorter stents rather than a
      single longer stent into such a curved artery represents a promising concept, but
      little is known about the impact of such an approach. The objective of this study
      is to evaluate the effectiveness of using a multiple segment stent rather than a
      single long stent to dilate a curved artery using the finite element method. A
      double segment stent (DSS) and a single segment stent (SSS) were modeled. The
      stents were compared when expanded into a model of a curved artery. The model
      predicts that the DSS provides higher flexibility, more conformity, and lower
      recoil in comparison to the SSS. The volume of arterial tissue experiencing high
      levels of stress due to stent implantation is also reduced for the DSS. It is
      suggested that a multiple segment stenting system is a potential solution to the
      problem of higher rates of in-stent restenosis in curved arteries and
      mechanically challenging environments.

PMID- 21950904
TI  - Penetrating annulus fibrosus injuries affect dynamic compressive behaviors of the
      intervertebral disc via altered fluid flow: an analytical interpretation.
AB  - Extensive experimental work on the effects of penetrating annular injuries
      indicated that large injuries impact axial compressive properties of small animal
      intervertebral discs, yet there is some disagreement regarding the sensitivity of
      mechanical tests to small injury sizes. In order to understand the mechanism of
      injury size sensitivity, this study proposed a simple one dimensional model
      coupling elastic deformations in the annulus with fluid flow into and out of the
      nucleus through both porous boundaries and through a penetrating annular injury.
      The model was evaluated numerically in dynamic compression with parameters
      obtained by fitting the solution to experimental stress-relaxation data. The
      model predicted low sensitivity of mechanical changes to injury diameter at both
      small and large sizes (as measured by low and high ratios of injury diameter to
      annulus thickness), with a narrow range of high sensitivity in between. The size
      at which axial mechanics were most sensitive to injury size (i.e., critical
      injury size) increased with loading frequency. This study provides a quantitative
      hypothetical model of how penetrating annulus fibrosus injuries in discs with a
      gelatinous nucleus pulposus may alter disc mechanics by changing nucleus pulposus
      fluid pressurization through introduction of a new fluid transport pathway though
      the annulus. This model also explains how puncture-induced biomechanical changes
      depend on both injury size and test protocol.

PMID- 21950905
TI  - Automatic sound speed selection in photoacoustic image reconstruction using an
      autofocus approach.
AB  - The reconstruction of images in photoacoustic tomography is reliant on specifying
      the speed of sound within the propagation medium. However, for in vivo imaging,
      this value is not normally accurately known. Here, an autofocus approach for
      automatically selecting the sound speed is proposed. This is based on maximizing
      the sharpness of the reconstructed image as quantified by a focus function.
      Several focus functions are investigated, and their performance is discussed. The
      method is demonstrated using phantom measurements made in a medium with a known
      sound speed and in vivo measurements of the vasculature in the flank of an adult
      mouse.

PMID- 21950906
TI  - Laser speckle contrast imaging of cerebral blood flow in freely moving animals.
AB  - We designed a miniature laser speckle imager that weighs ~20 g and is 3.1-cm high
      for full-field high-resolution imaging of cerebral blood flow (CBF) in freely
      moving animals. Coherent laser light illuminates the cortex through a multimode
      optical fiber bundle fixed onto the supporting frame of the imager. The reflected
      lights are then collected by a miniature macrolens system and imaged by a high
      resolution CMOS camera at a high frame rate (50 fps). Using this miniature
      imager, we achieve high spatiotemporal resolution laser speckle contrast imaging
      of CBF in freely moving animals in real time.

PMID- 21950907
TI  - Optical scattering coefficient estimated by optical coherence tomography
      correlates with collagen content in ovarian tissue.
AB  - Optical scattering coefficient from ex vivo unfixed normal and malignant ovarian
      tissue was quantitatively extracted by fitting optical coherence tomography (OCT)
      A-line signals to a single scattering model. 1097 average A-line measurements at
      a wavelength of 1310 nm were performed at 108 sites obtained from 18 ovaries. The
      average scattering coefficient obtained from the normal tissue group consisted of
      833 measurements from 88 sites was 2.41 mm(-1) (+/- 0.59), while the average
      coefficient obtained from the malignant tissue group consisted of 264
      measurements from 20 sites was 1.55 mm(-1) (+/- 0.46). The malignant ovarian
      tissue showed significant lower scattering than the normal group (p < 0.001). The
      amount of collagen within OCT imaging depth was analyzed from the tissue
      histological section stained with Sirius Red. The average collagen area fraction
      (CAF) obtained from the normal tissue group was 48.4% (+/- 12.3%), while the
      average CAF obtained from the malignant tissue group was 11.4% (+/- 4.7%). A
      statistical significance of the collagen content was found between the two groups
      (p < 0.001). These results demonstrated that quantitative measurements of optical
      scattering coefficient from OCT images could be a potential powerful method for
      ovarian cancer detection.

PMID- 21950908
TI  - Three-dimensional photoacoustic tomography based on the focal-line concept.
AB  - A full ring ultrasonic array-based photoacoustic tomography system was recently
      developed for small animal brain imaging. The 512-element array is cylindrically
      focused in the elevational direction, and can acquire a two-dimensional (2D)
      image in 1.6 s. In this letter, we demonstrate the three-dimensional (3D) imaging
      capability of this system. A novel 3D reconstruction algorithm was developed
      based on the focal-line concept. Compared to 3D images acquired simply by
      stacking a series of 2D images, the 3D focal-line reconstruction method renders
      images with much less artifacts, and improves the elevational resolution by 30%
      and the signal-to-noise ratio by two times. The effectiveness of the proposed
      algorithm was first validated by numerical simulations and then demonstrated with
      a hair phantom experiment and an ex vivo mouse embryo experiment.

PMID- 21950910
TI  - Optical delivery of liposome encapsulated chemical stimuli to neuronal cells.
AB  - Spatially confined and precise time delivery of neuroactive molecules is an
      important issue in neurophysiology. In this work we developed a technique for
      delivering chemical stimuli to cultured neurons consisting in encapsulating the
      molecules of interest in liposomes. These vectors were then loaded in reservoirs
      consisting of glass capillaries. The reservoirs were placed in the recording
      chamber and single liposomes were trapped and transported out by optical tweezers
      to the site of stimulation on cultured neurons. Finally, the release of liposome
      content was induced by application of UV-pulses, breaking the liposome membrane.
      The efficiency of encapsulation and release were first evaluated by loading the
      liposomes with fluorescein. In order to test the effect of the UV-induced
      release, liposomes with diameter ranging from 1 to 10 MUm (fL to pL volumes),
      were filled with KCl and tested on neuronal cells. Neuronal cultures, loaded with
      Ca(2+) dye, were monitored by imaging intracellular Ca(2+). An efficient release
      from the liposomes was demonstrated by detectable calcium signals, indicating
      stimulated depolarization of the neuronal cells by KCl. The present technique
      represents an alternative method for focal chemical stimulation of cultured cells
      that circumvents some of the limitations of microejection and photorelease of
      caged compounds.

PMID- 21950909
TI  - Functional photoacoustic imaging to observe regional brain activation induced by
      cocaine hydrochloride.
AB  - Photoacoustic microscopy (PAM) was used to detect small animal brain activation
      in response to drug abuse. Cocaine hydrochloride in saline solution was injected
      into the blood stream of Sprague Dawley rats through tail veins. The rat brain
      functional change in response to the injection of drug was then monitored by the
      PAM technique. Images in the coronal view of the rat brain at the locations of
      1.2 and 3.4 mm posterior to bregma were obtained. The resulted photoacoustic (PA)
      images showed the regional changes in the blood volume. Additionally, the
      regional changes in blood oxygenation were also presented. The results
      demonstrated that PA imaging is capable of monitoring regional hemodynamic
      changes induced by drug abuse.

PMID- 21950911
TI  - Quantitative analysis of dehydration in porcine skin for assessing mechanism of
      optical clearing.
AB  - Dehydration induced by optical clearing agents (OCAs) can improve tissue optical
      transmittance; however, current studies merely gave some qualitative
      descriptions. We develop a model to quantitatively evaluate water content with
      partial least-squares method based on the measurements of near-infrared
      reflectance spectroscopy and weight of porcine skin. Furthermore, a commercial
      spectrometer with an integrating sphere is used to measure the transmittance and
      reflectance of skin after treatment with different OCAs, and then the water
      content and optical properties of sample are calculated, respectively. The
      results show that both the reduced scattering coefficient and dehydration of skin
      decrease with prolongation of action of OCAs, but the relative change in former
      is larger than that in latter after a 60-min treatment. The absorption
      coefficient at 1450 nm decreases completely coincident with dehydration of skin.
      Further analysis illustrates that the correlation coefficient between the
      relative changes in the reduced scattering coefficient and dehydration is ~1
      during the 60-min treatment of agents, but there is an extremely significant
      difference between the two parameters for some OCAs with more hydroxyl groups,
      especially, glycerol or D-sorbitol, which means that the dehydration is a main
      mechanism of skin optical clearing, but not the only mechanism.

PMID- 21950912
TI  - Common-path low-coherence interferometry fiber-optic sensor guided microincision.
AB  - We propose and demonstrate a common-path low-coherence interferometry (CP-LCI)
      fiber-optic sensor guided precise microincision. The method tracks the target
      surface and compensates the tool-to-surface relative motion with better than +/-
      5 MUm resolution using a precision micromotor connected to the tool tip. A single
      fiber distance probe integrated microdissector was used to perform an accurate
      100 MUm incision into the surface of an Intralipid phantom. The CP-LCI guided
      incision quality in terms of depth was evaluated afterwards using three
      dimensional Fourier-domain optical coherence tomography imaging, which showed
      significant improvement of incision accuracy compared to free-hand-only
      operations.

PMID- 21950913
TI  - Color stability of maxillofacial silicone with nanoparticle pigment and opacifier
      submitted to disinfection and artificial aging.
AB  - The purpose of this study was to evaluate the color stability of a maxillofacial
      elastomer with the addition of a nanoparticle pigment and/or an opacifier
      submitted to chemical disinfection and artificial aging. Specimens were divided
      into four groups (n = 30): group I: silicone without pigment or opacifier, group
      II: ceramic powder pigment, group III: Barium sulfate (BaSO(4)) opacifier, and
      group IV: ceramic powder and BaSO(4) opacifier. Specimens of each group (n = 10)
      were disinfected with effervescent tablets, neutral soap, or 4% chlorhexidine
      gluconate. Disinfection was done three times a week during two months. Afterward,
      specimens were submitted to different periods of artificial aging. Color
      evaluation was initially done, after 60 days (disinfection period) and after 252,
      504, and 1008 h of artificial aging with aid of a reflection spectrophotometer.
      Data were analyzed by three-way ANOVA and Tukey test (alpha = 0.05). The isolated
      factor disinfection did not statistically influence the values of color stability
      among groups. The association between pigment and BaSO(4) opacifier (GIV) was
      more stable in relationship to color change (?E). All values of ?E obtained,
      independent of the disinfectant and the period of artificial aging, were
      considered acceptable in agreement with the norms presented in literature.

PMID- 21950914
TI  - Measuring integrated cellular mechanical stress response at focal adhesions by
      optical tweezers.
AB  - The ability of cells to sustain mechanical stress is largely modulated by the
      cytoskeleton. We present a new application of optical tweezers to study cell's
      mechanical properties. We trap a fibronectin-coated bead attached to an adherent
      H4II-EC3 rat hepatoma cell in order to apply the force to the cell surface
      membrane. The bead position corresponding to the cell's local mechanical response
      at focal adhesions is measured with a quadrant detector. We assessed the cell
      response by tracking the evolution of the equilibrium force for 40 cells selected
      at random and selected a temporal window to assess the cell initial force
      expression at focal adhesions. The mean value of the force within this time
      window over 40 randomly selected bead/cell bounds was 52.3 pN. Then, we assessed
      the responses of the cells with modulation of the cytoskeletons, namely the
      ubiquitous actin-microfilaments and microtubules, plus the differentiation
      dependent keratin intermediate filaments. Notably, a destabilization of the first
      two networks led to around 50 and 30% reductions in the mean equilibrium forces,
      respectively, relative to untreated cells, whereas a loss of the third one
      yielded a 25% increase. The differences in the forces from untreated and treated
      cells are resolved by the optical tweezers experiment.

PMID- 21950915
TI  - Azimuthal phase retardation microscope for visualizing actin filaments of
      biological cells.
AB  - We developed a new theory-based azimuthal phase retardation microscope to
      visualize distributions of actin filaments in biological cells without having
      them with exogenous dyes, fluorescence labels, or stains. The azimuthal phase
      retardation microscope visualizes distributions of actin filaments by measuring
      the intensity variations of each pixel of a charge coupled device camera while
      rotating a single linear polarizer. Azimuthal phase retardation delta between two
      fixed principal axes was obtained by calculating the rotation angles of the
      polarizer at the intensity minima from the acquired intensity data. We have
      acquired azimuthal phase retardation distributions of human breast cancer cell,
      MDA MB 231 by our microscope and compared the azimuthal phase retardation
      distributions with the fluorescence image of actin filaments by the commercial
      fluorescence microscope. Also, we have observed movement of human umbilical cord
      blood derived mesenchymal stem cells by measuring azimuthal phase retardation
      distributions.

PMID- 21950916
TI  - Optical coherence tomography to investigate optical properties of blood during
      coagulation.
AB  - This study investigates the optical properties of human blood during the
      coagulation process under statics using optical coherence tomography (OCT). OCT
      signal slope (OCTSS) and 1/e light penetration depth (d(1/e)) were obtained from
      the profiles of reflectance versus depth. Results showed that both OCTSS and
      d(1/e) were able to sensitively differentiate various stages of blood properties
      during coagulating. After 1 h clotting, OCTSS decreased by 47.0%, 15.0%, 13.7%,
      and 8.5% and d(1/e) increased by 34.7%, 29.4%, 24.3%, and 22.9% for the blood
      samples at HCT of 25%, 35%, 45%, and 55%, respectively. The slope of d(1/e)
      versus time (S(r), *10(-4) mm/s), associated with clot formation rate decreased
      from 6.0 +/- 0.3, 3.7 +/- 0.5 to 2.3 +/- 0.4 with the increasing of HCT from 35%,
      45%, to 55%. The clotting time (t(c)) from the d(1/e) evolution curves was
      estimated to be 1969 +/- 92 s, 375 +/- 12 s, 455 +/- 11 s, and 865 +/- 47 s for
      the blood of 25%, 35%, 45%, and 55%. This study demonstrates that the parameters
      (t(c) and S(r)) from the variations in d(1/e) had better sensitivity and smaller
      standard deviation. Furthermore, blood hematocrit affecting backscattering
      properties of blood during coagulation was capable of being discerned by OCT
      parameters. It is concluded that OCT is a potential technique to quantify and
      follow the liquid-gel transition of blood during clotting.

PMID- 21950917
TI  - Optical coherent tomography: promising in vivo measurement of hair shaft cross
      section.
AB  - Variations in hair shaft morphology reflect ethnical diversity, but may also
      indicate internal diseases, nutritional deficiency, or hair and scalp disorders.
      The measurement and the follow-up of the hair shaft thickness over a defined
      period of time would be a valuable diagnostic tool in clinical practice. Standard
      light microscopy (LM) measurements require the epilation of hair shafts and
      frequently yield inaccurate values caused by the elliptic geometry of human hair
      shafts. Optical coherence tomography (OCT) is a noninvasive investigation method
      based on the principles of Michelson interferometry with a detection depth of
      approximately 1 mm in human skin. Two-dimensional images of the cross sections of
      tissue samples at a resolution of approximately 10 MUm are produced, which allows
      convenient calculation of hair shaft thickness. To evaluate this new methodology
      for hair shaft thickness measurements, hair shafts taken from 28 healthy
      volunteers were analyzed by in vivo OCT and compared to standard in vitro LM
      measurements of hair shaft thickness. OCT yielded highly reproducible
      measurements of hair shaft thickness with a distinctly reduced variation compared
      to standard LM. This technique offers a unique opportunity for in vivo
      measurement and a follow-up of the kinetics of hair shaft thickness in humans
      during medical therapy.

PMID- 21950918
TI  - On-the-spot lung cancer differential diagnosis by label-free, molecular
      vibrational imaging and knowledge-based classification.
AB  - We report the development and application of a knowledge-based coherent anti
      Stokes Raman scattering (CARS) microscopy system for label-free imaging, pattern
      recognition, and classification of cells and tissue structures for
      differentiating lung cancer from non-neoplastic lung tissues and identifying lung
      cancer subtypes. A total of 1014 CARS images were acquired from 92 fresh frozen
      lung tissue samples. The established pathological workup and diagnostic cellular
      were used as prior knowledge for establishment of a knowledge-based CARS system
      using a machine learning approach. This system functions to separate normal, non
      neoplastic, and subtypes of lung cancer tissues based on extracted quantitative
      features describing fibrils and cell morphology. The knowledge-based CARS system
      showed the ability to distinguish lung cancer from normal and non-neoplastic lung
      tissue with 91% sensitivity and 92% specificity. Small cell carcinomas were
      distinguished from nonsmall cell carcinomas with 100% sensitivity and
      specificity. As an adjunct to submitting tissue samples to routine pathology, our
      novel system recognizes the patterns of fibril and cell morphology, enabling
      medical practitioners to perform differential diagnosis of lung lesions in mere
      minutes. The demonstration of the strategy is also a necessary step toward in
      vivo point-of-care diagnosis of precancerous and cancerous lung lesions with a
      fiber-based CARS microendoscope.

PMID- 21950919
TI  - Spontaneous ultraweak photon emission imaging of oxidative metabolic processes in
      human skin: effect of molecular oxygen and antioxidant defense system.
AB  - All living organisms emit spontaneous ultraweak photon emission as a result of
      cellular metabolic processes. In this study, the involvement of reactive oxygen
      species (ROS) formed as the byproduct of oxidative metabolic processes in
      spontaneous ultraweak photon emission was studied in human hand skin. The effect
      of molecular oxygen and ROS scavengers on spontaneous ultraweak photon emission
      from human skin was monitored using a highly sensitive photomultiplier tube and
      charged coupled device camera. When spontaneous ultraweak photon emission was
      measured under anaerobic conditions, the photon emission was decreased, whereas
      under hyperaerobic condition the enhancement in photon emission was observed.
      Spontaneous ultraweak photon emission measured after topical application of
      glutathione, alpha-tocopherol, ascorbate, and coenzyme Q10 was observed to be
      decreased. These results reveal that ROS formed during the cellular metabolic
      processes in the epidermal cells play a significant role in the spontaneous
      ultraweak photon emission. It is proposed that spontaneous ultraweak photon
      emission can be used as a noninvasive tool for the temporal and spatial
      monitoring of the oxidative metabolic processes and intrinsic antioxidant system
      in human skin.

PMID- 21950920
TI  - Infrared spectroscopic imaging of renal tumor tissue.
AB  - Fourier transform infrared (FTIR) spectroscopic imaging has been used to probe
      the biochemical composition of human renal tumor tissue and adjacent normal
      tissue. Freshly resected renal tumor tissue from surgery was prepared as a thin
      cryosection and examined by FTIR spectroscopic imaging. Tissue types could be
      discriminated by utilizing a combination of fuzzy k-means cluster analysis and a
      supervised classification algorithm based on a linear discriminant analysis. The
      spectral classification is compared and contrasted with the histological stained
      image. It is further shown that renal tumor cells have spread in adjacent normal
      tissue. This study demonstrates that FTIR spectroscopic imaging can potentially
      serve as a fast and objective approach for discrimination of renal tumor tissue
      from normal tissue and even in the detection of tumor infiltration in adjacent
      tissue.

PMID- 21950921
TI  - Rotationally acquired four-dimensional optical coherence tomography of embryonic
      chick hearts using retrospective gating on the common central A-scan.
AB  - We introduce a new method of rotational image acquisition for four-dimensional
      (4D) optical coherence tomography (OCT) of beating embryonic chick hearts. The
      rotational axis and the central A-scan of the OCT are identical. An out-of-phase
      image sequence covering multiple heartbeats is acquired at every angle of an
      incremental rotation of the deflection mirrors of the OCT system. Image
      acquisition is accomplished after a rotation of 180 degrees . Comparison of a
      displayed live M-mode of the central A-scan with a reference M-mode allows
      instant detection of translational movements of the embryo. For calculation of 4D
      data sets, we apply an image-based retrospective gating algorithm using the phase
      information of the common central A-scan present in all acquired images. This
      leads to cylindrical three-dimensional data sets for every time step of the
      cardiac cycle that can be used for 4D visualization. We demonstrate this approach
      and provide a video of a beating Hamburger and Hamilton stage 16 embryonic chick
      heart generated from a 4D OCT data set using rotational image acquisition.

PMID- 21950923
TI  - Automated determination of cup-to-disc ratio for classification of glaucomatous
      and normal eyes on stereo retinal fundus images.
AB  - Early diagnosis of glaucoma, which is the second leading cause of blindness in
      the world, can halt or slow the progression of the disease. We propose an
      automated method for analyzing the optic disc and measuring the cup-to-disc ratio
      (CDR) on stereo retinal fundus images to improve ophthalmologists' diagnostic
      efficiency and potentially reduce the variation on the CDR measurement. The
      method was developed using 80 retinal fundus image pairs, including 25
      glaucomatous, and 55 nonglaucomatous eyes, obtained at our institution. A disc
      region was segmented using the active contour method with the brightness and edge
      information. The segmentation of a cup region was performed using a depth map of
      the optic disc, which was reconstructed on the basis of the stereo disparity. The
      CDRs were measured and compared with those determined using the manual
      segmentation results by an expert ophthalmologist. The method was applied to a
      new database which consisted of 98 stereo image pairs including 60 and 30 pairs
      with and without signs of glaucoma, respectively. Using the CDRs, an area under
      the receiver operating characteristic curve of 0.90 was obtained for
      classification of the glaucomatous and nonglaucomatous eyes. The result indicates
      potential usefulness of the automated determination of CDRs for the diagnosis of
      glaucoma.

PMID- 21950922
TI  - Protoporphyrin IX fluorescence contrast in invasive glioblastomas is linearly
      correlated with Gd enhanced magnetic resonance image contrast but has higher
      diagnostic accuracy.
AB  - The sensitivity and specificity of in vivo magnetic resonance (MR) imaging is
      compared with production of protoporphyrin IX (PpIX), determined ex vivo, in a
      diffusely infiltrating glioma. A human glioma transfected with green fluorescent
      protein, displaying diffuse, infiltrative growth, was implanted intracranially in
      athymic nude mice. Image contrast from corresponding regions of interest (ROIs)
      in in vivo MR and ex vivo fluorescence images was quantified. It was found that
      all tumor groups had statistically significant PpIX fluorescence contrast and
      that PpIX contrast demonstrated the best predictive power for tumor presence.
      Contrast from gadolinium enhanced T1-weighted (T1W+Gd) and absolute T2 images
      positively predicted the presence of a tumor, confirmed by the GFP positive
      (GFP+) and hematoxylin and eosin positive (H&E+) ROIs. However, only the absolute
      T2 images had predictive power from controls in ROIs that were GFP+ but H&E
      negative. Additionally, PpIX fluorescence and T1W+Gd image contrast were linearly
      correlated in both the GFP+ (r = 0.79, p<1*10(-8)) and H&E+ (r = 0.74, p<0.003)
      ROIs. The trace diffusion images did not have predictive power or significance
      from controls. This study indicates that gadolinium contrast enhanced MR images
      can predict the presence of diffuse tumors, but PpIX fluorescence is a better
      predictor regardless of tumor vascularity.

PMID- 21950924
TI  - In vivo fluorescence confocal microscopy: indocyanine green enhances the contrast
      of epidermal and dermal structures.
AB  - In recent years, in vivo skin imaging devices have been successfully implemented
      in skin research as well as in clinical routine. Of particular importance is the
      use of reflectance confocal microscopy (RCM) and fluorescence confocal microscopy
      (FCM) that enable visualization of the tissue with a resolution comparable to
      histology. A newly developed commercially available multi-laser device in which
      both technologies are integrated now offers the possibility to directly compare
      RCM with FCM. The fluorophore indocyanine green (ICG) was intradermally injected
      into healthy forearm skin of 10 volunteers followed by in vivo imaging at various
      time points. In the epidermis, accurate assessment of cell morphology with FCM
      was supplemented by identification of pigmented cells and structures with RCM. In
      dermal layers, only with FCM connective tissue fibers were clearly contoured down
      to a depth of more than 100 MUm. The fluorescent signal still provided a
      favorable image contrast 24 and 48 hours after injection. Subsequently, ICG was
      applied to different types of skin diseases (basal cell carcinoma, actinic
      keratosis, seborrhoeic keratosis, and psoriasis) in order to demonstrate the
      diagnostic benefit of FCM when directly compared with RCM. Our data suggest a
      great impact of FCM in combination with ICG on clinical and experimental
      dermatology in the future.

PMID- 21950925
TI  - Follow-up of cortical activity and structure after lesion with laser speckle
      imaging and magnetic resonance imaging in nonhuman primates.
AB  - The nonhuman primate model is suitable to study mechanisms of functional recovery
      following lesion of the cerebral cortex (motor cortex), on which therapeutic
      strategies can be tested. To interpret behavioral data (time course and extent of
      functional recovery), it is crucial to monitor the properties of the experimental
      cortical lesion, induced by infusion of the excitotoxin ibotenic acid. In two
      adult macaque monkeys, ibotenic acid infusions produced a restricted, permanent
      lesion of the motor cortex. In one monkey, the lesion was monitored over 3.5
      weeks, combining laser speckle imaging (LSI) as metabolic readout (cerebral blood
      flow) and anatomical assessment with magnetic resonance imaging (T2-weighted
      MRI). The cerebral blood flow, measured online during subsequent injections of
      the ibotenic acid in the motor cortex, exhibited a dramatic increase, still
      present after one week, in parallel to a MRI hypersignal. After 3.5 weeks, the
      cerebral blood flow was strongly reduced (below reference level) and the
      hypersignal disappeared from the MRI scan, although the lesion was permanent as
      histologically assessed post-mortem. The MRI data were similar in the second
      monkey. Our experiments suggest that LSI and MRI, although they reflect different
      features, vary in parallel during a few weeks following an excitotoxic cortical
      lesion.

PMID- 21950926
TI  - Video-rate fluorescence lifetime imaging camera with CMOS single-photon avalanche
      diode arrays and high-speed imaging algorithm.
AB  - A high-speed and hardware-only algorithm using a center of mass method has been
      proposed for single-detector fluorescence lifetime sensing applications. This
      algorithm is now implemented on a field programmable gate array to provide fast
      lifetime estimates from a 32 * 32 low dark count 0.13 MUm complementary metal
      oxide-semiconductor single-photon avalanche diode (SPAD) plus time-to-digital
      converter array. A simple look-up table is included to enhance the lifetime
      resolvability range and photon economics, making it comparable to the commonly
      used least-square method and maximum-likelihood estimation based software. To
      demonstrate its performance, a widefield microscope was adapted to accommodate
      the SPAD array and image different test samples. Fluorescence lifetime imaging
      microscopy on fluorescent beads in Rhodamine 6G at a frame rate of 50 fps is also
      shown.

PMID- 21950927
TI  - Lipidots: competitive organic alternative to quantum dots for in vivo
      fluorescence imaging.
AB  - The use of fluorescent nanostructures can bring several benefits on the signal to
      background ratio for in vitro microscopy, in vivo small animal imaging, and image
      guided surgery. Fluorescent quantum dots (QDs) display outstanding optical
      properties, with high brightness and low photobleaching rate. However, because of
      their toxic element core composition and their potential long term retention in
      reticulo-endothelial organs such as liver, their in vivo human applications seem
      compromised. The development of new dye-loaded (DiO, DiI, DiD, DiR, and
      Indocyanine Green (ICG)) lipid nanoparticles for fluorescence imaging (lipidots)
      is described here. Lipidot optical properties quantitatively compete with those
      of commercial QDs (QTracker((r))705). Multichannel in vivo imaging of lymph nodes
      in mice is demonstrated for doses as low as 2 pmols of particles. Along with
      their optical properties, fluorescent lipidots display very low cytotoxicity
      (IC(50) > 75 nM), which make them suitable tools for in vitro, and especially in
      vivo, fluorescence imaging applications.

PMID- 21950928
TI  - Multichannel wearable system dedicated for simultaneous
      electroencephalography/near-infrared spectroscopy real-time data acquisitions.
AB  - Functional neuroimaging is becoming a valuable tool in cognitive research and
      clinical applications. The clinical context brings specific constraints that
      include the requirement of a high channel count to cover the whole head, high
      sensitivity for single event detection, and portability for long-term bedside
      monitoring. For epilepsy and stroke monitoring, the combination of
      electroencephalography (EEG) and functional near-infrared spectroscopy (NIRS) is
      expected to provide useful clinical information, and efforts have been deployed
      to create prototypes able to simultaneously acquire both measurement modalities.
      However, to the best of our knowledge, existing systems lack portability, NIRS
      sensitivity, or have low channel count. We present a battery-powered, portable
      system with potentially up to 32 EEG channels, 32 NIRS light sources, and 32
      detectors. Avalanche photodiodes allow for high NIRS sensitivity and the autonomy
      of the system is over 24 h. A reduced channel count prototype with 8 EEG
      channels, 8 sources, and 8 detectors was tested on phantoms. Further validation
      was done on five healthy adults using a visual stimulation protocol to detect
      local hemodynamic changes and visually evoked potentials. Results show good
      concordance with literature regarding functional activations and suggest
      sufficient performance for clinical use, provided some minor adjustments were
      made.

PMID- 21950929
TI  - Spectrally resolved multidepth fluorescence imaging.
AB  - We present a multicolor fluorescence imaging modality to visualize in real-time
      tissue structures emitting multispectral fluorescent light from different focal
      depths. Each designated spectrum of fluorescent emission from a specific depth
      within a volumetric tissue is probed by a depth-spectrum selective holographic
      grating. The grating for each fluorescent color are multiplexed within a volume
      hologram, which enables simultaneously obtaining multicolored fluorescent
      information at different depths within a biological tissue sample. We demonstrate
      the imaging modality's ability to obtain laser-induced multicolored fluorescence
      images of a biological sample from different depths without scanning. We also
      experimentally demonstrate that the imaging modality can be simultaneously
      operated at both fluorescent and bright field modes to provide complementary
      information of volumetric tissue structures at different depths in real-time.

PMID- 21950930
TI  - Quantitative photoacoustic imaging: correcting for heterogeneous light fluence
      distributions using diffuse optical tomography.
AB  - The specificity of molecular and functional photoacoustic (PA) images depends on
      the accuracy of the photoacoustic absorption spectroscopy. The PA signal is
      proportional to the product of the optical absorption coefficient and local light
      fluence; quantitative PA measurements of the optical absorption coefficient
      therefore require an accurate estimation of optical fluence. Light-modeling aided
      by diffuse optical tomography (DOT) can be used to map the required fluence and
      to reduce errors in traditional PA spectroscopic analysis. As a proof-of-concept,
      we designed a tissue-mimicking phantom to demonstrate how fluence-related
      artifacts in PA images can lead to misrepresentations of tissue properties. To
      correct for these inaccuracies, the internal fluence in the tissue phantom was
      estimated by using DOT to reconstruct spatial distributions of the absorption and
      reduced scattering coefficients of multiple targets within the phantom. The
      derived fluence map, which only consisted of low spatial frequency components,
      was used to correct PA images of the phantom. Once calibrated to a known
      absorber, this method reduced errors in estimated absorption coefficients from
      33% to 6%. These results experimentally demonstrate that combining DOT with PA
      imaging can significantly reduce fluence-related errors in PA images, while
      producing quantitatively accurate, high-resolution images of the optical
      absorption coefficient.

PMID- 21950931
TI  - Recognition of serous ovarian tumors in human samples by multimodal nonlinear
      optical microscopy.
AB  - We used a multimodal nonlinear optics microscopy, specifically two-photon excited
      fluorescence (TPEF), second and third harmonic generation (SHG/THG) microscopies,
      to observe pathological conditions of ovarian tissues obtained from human
      samples. We show that strong TPEF + SHG + THG signals can be obtained in fixed
      samples stained with hematoxylin and eosin (H&E) stored for a very long time, and
      that H&E staining enhanced the THG signal. We then used the multimodal TPEF-SHG
      THG microscopies in a stored file of H&E stained samples of human ovarian cancer
      to obtain complementary information about the epithelium/stromal interface, such
      as the transformation of epithelium surface (THG) and the overall fibrillary
      tissue architecture (SHG). This multicontrast nonlinear optics microscopy is able
      to not only differentiate between cancerous and healthy tissue, but can also
      distinguish between normal, benign, borderline, and malignant specimens according
      to their collagen disposition and compression levels within the extracellular
      matrix. The dimensions of the layers of epithelia can also be measured precisely
      and automatically. Our data demonstrate that optical techniques can detect
      pathological changes associated with ovarian cancer.

PMID- 21950932
TI  - Fluorescence lifetime imaging for the characterization of the biochemical
      composition of atherosclerotic plaques.
AB  - This study investigates the ability of a flexible fiberoptic-based fluorescence
      lifetime imaging microscopy (FLIM) technique to resolve biochemical features in
      plaque fibrotic cap associated with plaque instability and based solely on
      fluorescence decay characteristics. Autofluorescence of atherosclerotic human
      aorta (11 autopsy samples) was measured at 48 locations through two filters,
      F377: 377/50 and F460: 460/60 nm (center wavelength/bandwidth). The fluorescence
      decay dynamic was described by average lifetime (tau) and four Laguerre
      coefficients (LECs) retrieved through a Laguerre deconvolution technique. FLIM
      derived parameters discriminated between four groups [elastin-rich (ER), elastin
      and macrophage-rich (E+M), collagen-rich (CR), and lipid-rich (LR)]. For example,
      tau(F377) discriminated ER from CR (R = 0.84); tau(F460) discriminated E+M from
      CR and ER (R = 0.60 and 0.54, respectively); LEC-1(F377) discriminated CR from LR
      and E+M (R = 0.69 and 0.77, respectively); P < 0.05 for all correlations. Linear
      discriminant analysis was used to classify this data set with specificity >87%
      (all cases) and sensitivity as high as 86%. Current results demonstrate for the
      first time that clinically relevant features (e.g., ratios of lipid versus
      collagen versus elastin) can be evaluated with a flexible-fiber based FLIM
      technique without the need for fluorescence intensity information or contrast
      agents.

PMID- 21950933
TI  - Optical microangiography provides an ability to monitor responses of cerebral
      microcirculation to hypoxia and hyperoxia in mice.
AB  - In vivo imaging of microcirculation can improve our fundamental understanding of
      cerebral microhemodynamics under various physiological challenges, such as
      hypoxia and hyperoxia. However, existing techniques often involve the use of
      invasive procedures or exogenous contrast agents, which would inevitably perturb
      the intrinsic physiologic responses of microcirculation being investigated. We
      report ultrahigh sensitive optical microangiography (OMAG) for label-free
      monitoring of microcirculation responses challenged by oxygen inhalation. For the
      first time, we demonstrate that OMAG is capable of showing the impact of acute
      hypoxia and hyperoxia on microhemodynamic activities, including the passive and
      active modulation of microvascular density and flux regulation, within capillary
      and noncapillary vessels in rodents in vivo. The ability of OMAG to functionally
      image the intact microcirculation promises future applications for studying
      cerebral diseases.

PMID- 21950934
TI  - Simultaneous optical mapping of transmembrane potential and wall motion in
      isolated, perfused whole hearts.
AB  - Optical mapping of cardiac propagation has traditionally been hampered by motion
      artifact, chiefly due to changes in photodetector-to-tissue registration as the
      heart moves. We have developed an optical mapping technique to simultaneously
      record electrical waves and mechanical contraction in isolated hearts. This
      allows removal of motion artifact from transmembrane potential (V(m)) recordings
      without the use of electromechanical uncoupling agents and allows the interplay
      of electrical and mechanical events to be studied at the whole organ level.
      Hearts are stained with the voltage-sensitive dye di-4-ANEPPS and ring-shaped
      markers are attached to the epicardium. Fluorescence, elicited on alternate
      frames by 450 and 505 nm light-emitting diodes, is recorded at 700 frames/ per
      second by a camera fitted with a 605 +/- 25 nm emission filter. Marker positions
      are tracked in software. A signal, consisting of the temporally interlaced 450
      and 505 nm fluorescence, is collected from the pixels enclosed by each moving
      ring. After deinterlacing, the 505 nm signal consists of V(m) with motion
      artifact, while the 450 nm signal is minimally voltage-sensitive and contains
      primarily artifacts. The ratio of the two signals estimates V(m). Deformation of
      the tissue enclosed by each set of 3 rings is quantified using homogeneous finite
      strain.

PMID- 21950935
TI  - Initial results of imaging melanoma metastasis in resected human lymph nodes
      using photoacoustic computed tomography.
AB  - The pathological status of the sentinel lymph node is important for accurate
      melanoma staging, ascertaining prognosis and planning treatment. The standard
      procedure involves biopsy of the node and histopathological assessment of its
      status. Drawbacks of this examination include a finite sampling of the node with
      the likelihood of missing metastases, and a significant time-lag before
      histopathological results are available to the surgeon. We studied the
      applicability of photoacoustic computed tomographic imaging as an intraoperative
      modality for examining the status of resected human sentinel lymph nodes. We
      first applied the technique to image ex vivo pig lymph nodes carrying metastases
      simulating melanoma cells using multiple wavelengths. The experience gained was
      applied to image a suspect human lymph node. We validated the photoacoustic
      imaging results by comparing a reconstructed slice with a histopathological
      section through the node. Our results suggest that photoacoustics has the
      potential to develop into an intraoperative imaging method to detect melanoma
      metastases in sentinel lymph nodes.

PMID- 21950937
TI  - In vitro tympanic membrane position identification with a co-axial fiber-optic
      otoscope.
AB  - Otitis media diagnosis can be assisted by measuring the shape of the tympanic
      membrane. We have developed an ear speculum for an otoscope, including spatially
      distributed source and detector optical fibers, to generate source-detector
      intensity matrices (SDIMs), representing the curvature of surfaces. The surfaces
      measured were a model ear with a latex membrane and harvested temporal bones
      including intact tympanic membranes. The position of the tympanic membrane was
      shifted from retracted to bulging by air pressure and that of the latex membrane
      by water displacement. The SDIM was normalized utilizing both external (a sheared
      flat plastic cylinder) and internal references (neutral position of the
      membrane). Data was fitted to a two-dimensional Gaussian surface representing the
      shape by its amplitude and offset. Retracted and bulging surfaces were
      discriminated for the model ear by the sign of the Gaussian amplitude for both
      internal and external reference normalization. Tympanic membranes were separated
      after a two-step normalization: first to an external reference, adjusted for the
      distance between speculum and the surfaces, and second by comparison with an
      average normally positioned SDIM from tympanic membranes. In conclusion, we have
      shown that the modified otoscope can discriminate between bulging and retracted
      tympanic membranes in a single measurement, given a two-step normalization.

PMID- 21950936
TI  - Measurement of the complex refractive index of tissue-mimicking phantoms and
      biotissue by extended differential total reflection method.
AB  - Refractive index of biotissue is a useful optical parameter in the biomedical
      field. An extended differential total reflection method is introduced to
      determine the complex refractive index. The real part is directly determined by
      differential of the reflectance curve, and the imaginary part is obtained from
      nonlinear fitting. The method is verified by a series of tissue-mimicking
      phantoms, porcine muscle and porcine adipose.

PMID- 21950938
TI  - Optical properties of neonatal skin measured in vivo as a function of age and
      skin pigmentation.
AB  - Knowledge of the optical properties of neonatal skin is invaluable when
      developing new, or improving existing optical techniques for use at the neonatal
      intensive care. In this article, we present in vivo measurements of the
      absorption MU(a) and reduced scattering coefficient MU(s) (') of neonatal skin
      between 450 and 600 nm and assess the influence of age and skin pigmentation on
      the optical properties. The optical properties were measured using a spatially
      resolved, steady state diffuse reflectance spectroscopy setup, combined with a
      modified spatially resolved diffusion model. The method was validated on phantoms
      with known values for the absorption and reduced scattering coefficient. Values
      of MU(a) and MU(s) (') were obtained from the skin at four different body
      locations (forehead, sternum, hand, and foot) of 60 neonates with varying
      gestational age, postnatal age, and skin pigmentation. We found that MU(a) ranged
      from 0.02 to 1.25 mm(-1) and MU(s) (') was in the range of 1 to 2.8 mm(-1) (5th
      to 95th percentile of the patient population), independent of body location. In
      contrast to previous studies, no to very weak correlation was observed between
      the optical properties and gestational maturity, but a strong dependency of the
      absorption coefficient on postnatal age was found for dark skinned patients.

PMID- 21950939
TI  - Reproducibility of cerebral tissue oxygen saturation measurements by near
      infrared spectroscopy in newborn infants.
AB  - Early detection of cerebral hypoxemia is an important aim in neonatology. A
      relevant parameter to assess brain oxygenation may be the cerebral tissue oxygen
      saturation (StO(2)) measured by near-infrared spectroscopy (NIRS). So far the
      reproducibility of StO(2) measurements was too low for clinical application,
      probably due to inhomogeneities. The aim of this study was to test a novel sensor
      geometry which reduces the influence of inhomogeneities. Thirty clinically stable
      newborn infants, with a gestational age of median 33.9 (range 26.9 to 41.9)
      weeks, birth weight of 2220 (820 to 4230) g, postnatal age of 5 (1 to 71) days
      were studied. At least four StO(2) measurements of 1 min duration were carried
      out using NIRS on the lateral head. The sensor was repositioned between
      measurements. Reproducibility was calculated by a linear mixed effects model. The
      mean StO(2) was 79.99 +/- 4.47% with a reproducibility of 2.76% and a between
      infant variability of 4.20%. Thus, the error of measurement only accounts for
      30.1% of the variability. The novel sensor geometry leads to considerably more
      precise measurements compared to previous studies with, e.g., ~5% reproducibility
      for the NIRO 300. The novel StO(2) values hence have a higher clinical relevance.

PMID- 21950940
TI  - Analyzing near-infrared scattering from human skin to monitor changes in
      hematocrit.
AB  - Probing tissue with near-infrared radiation (NIR) simultaneously produces
      remitted fluorescence and Raman scattering (IE) plus Rayleigh/Mie light
      scattering (EE) that noninvasively give chemical and physical information about
      the materials and objects within. We model tissue as a three-phase system: plasma
      and red blood cell (RBC) phases that are mobile and a static tissue phase. In
      vivo, any volume of tissue naturally experiences spatial and temporal
      fluctuations of blood plasma and RBC content. Plasma and RBC fractions may be
      discriminated from each other on the basis of their physical, chemical, and
      optical properties. Thus, IE and EE from NIR probing yield information about
      these fractions. Assuming there is no void volume in viable tissue, or that void
      volume is constant, changes in plasma and RBC volume fractions may be calculated
      from simultaneous measurements of the two observables, EE and IE. In a previously
      published analysis we showed the underlying phenomenology but did not provide an
      algorithm for calculating volume fractions from experimental data. Now, we
      present a simple analysis that allows monitoring of fluid fraction and hematocrit
      (Hct) changes by measuring IE and EE, and apply it to some experimental in vivo
      measurements.

PMID- 21950941
TI  - Multiple scattering model for the penetration depth of low-coherence enhanced
      backscattering.
AB  - Low-coherence enhanced backscattering (LEBS) is a depth-selective self
      interference phenomenon that originates from light traveling time-reversed paths
      in a scattering medium. The depth selectivity of LEBS and its sensitivity to
      optical properties of the scattering medium has made it a promising technique for
      probing the structure of biological tissue with applications to disease diagnosis
      and, in particular, precancerous conditions. The ability to accurately predict
      the penetration depth of the LEBS signal is important in targeting an optimal
      tissue depth for detecting precancerous cells. This prediction is further
      complicated by the variation in optical properties of different tissue types. In
      this paper, the effects of the reduced scattering coefficient (MU(s)'), the phase
      function and the instrument spatial coherence length (L(sc)) on the LEBS
      penetration depth are quantified. It is determined that the LEBS penetration
      depth is primarily dependent on L(sc), MU(s)', and the anisotropy factor (g), but
      has minimal dependence on higher moments of the phase function. An empirical
      expression, having a similar form as the double scattering approximation for
      LEBS, is found to accurately predict the average penetration depth in the
      multiple scattering regime. The expression is shown to be accurate for a broad
      range of experimentally relevant optical properties and spatial coherence
      lengths.

PMID- 21950943
TI  - Choosing optimal wavelength for photodynamic therapy of port wine stains by
      mathematic simulation.
AB  - Many laser wavelengths have been used in photodynamic therapy (PDT) for port wine
      stains (PWS). However, how these wavelengths result in different PDT outcomes has
      not been clearly illuminated. This study is designed to analyze which wavelengths
      would be the most advantageous for use in PDT for PWS. The singlet oxygen yield
      in PDT-treated PWS skin under different wavelengths at the same photosensitizer
      dosage was simulated and the following three situations were simulated and
      compared: 1. PDT efficiency of 488, 532, 510, 578, and 630 nm laser irradiation
      at clinical dosage (100 mW/cm(2), 40 min); 2. PDT efficiency of different
      wavelength for PWS with hyperpigmentation after previous PDT; 3. PDT efficiency
      of different wavelengths for PWS, in which only deeply located ectatic vessels
      remained. The results showed that singlet oxygen yield is the highest at 510 nm,
      it is similar at 532 nm and 488 nm, and very low at 578 nm and 630 nm. This
      result is identical to the state in clinic. According to this theoretical study,
      the optimal wavelength for PDT in the treatment of PWS should near the absorption
      peaks of photosensitizer and where absorption from native chromophores
      (haemoglobin and melanin) is diminished.

PMID- 21950942
TI  - Breast cancer spatial heterogeneity in near-infrared spectra and the prediction
      of neoadjuvant chemotherapy response.
AB  - We describe an algorithm to calculate an index that characterizes spatial
      differences in broadband near-infrared [(NIR), 650-1000 nm] absorption spectra of
      tumor-containing breast tissue. Patient-specific tumor spatial heterogeneities
      are visualized through a heterogeneity spectrum function (HS). HS is a biomarker
      that can be attributed to different molecular distributions within the tumor. To
      classify lesion heterogeneities, we built a heterogeneity index (HI) derived from
      the HS by weighing the HS in specific NIR absorption bands. It is shown that
      neoadjuvant chemotherapy (NAC) response is potentially related to the tumor
      heterogeneity. Therefore, we correlate the heterogeneity index obtained prior to
      treatment with the final response to NAC. From a pilot study of 15 cancer
      patients treated with NAC, pathological complete responders (pCR) were separated
      from non-pCR according to their HI (-44 +/- 12 and 43 +/- 17, p = 3 * 10(-8),
      respectively). We conclude that the HS function is a biomarker that can be used
      to visualize spatial heterogeneities in lesions, and the baseline HI prior to
      therapy correlates with chemotherapy pathological response.

PMID- 21950944
TI  - Targeted gene transfer into rat facial muscles by nanosecond pulsed laser-induced
      stress waves.
AB  - We investigate the feasibility of using nanosecond pulsed laser-induced stress
      waves (LISWs) for gene transfer into rat facial muscles. LISWs are generated by
      irradiating a black natural rubber disk placed on the target tissue with
      nanosecond pulsed laser light from the second harmonics (532 nm) of a Q-switched
      Nd:YAG laser, which is widely used in head and neck surgery and proven to be
      safe. After injection of plasmid deoxyribose nucleic acid (DNA) coding for Lac Z
      into rat facial muscles, pulsed laser is used to irradiate the laser target on
      the skin surface without incision or exposure of muscles. Lac Z expression is
      detected by X-gal staining of excised rat facial skin and muscles. Strong Lac Z
      expression is observed seven days after gene transfer, and sustained for up to 14
      days. Gene transfer is achieved in facial muscles several millimeters deep from
      the surface. Gene expression is localized to the tissue exposed to LISWs. No
      tissue damage from LISWs is observed. LISW is a promising nonviral target gene
      transfer method because of its high spatial controllability, easy applicability,
      and minimal invasiveness. Gene transfer using LISW to produce therapeutic
      proteins such as growth factors could be used to treat nerve injury and
      paralysis.

PMID- 21950945
TI  - The emergence of cerebral specialization for the human voice over the first
      months of life.
AB  - How specialized is the infant brain for processing voice within our environment?
      Research in adults suggests that portions of the temporal lobe play an important
      role in differentiating vocalizations from other environmental sounds; however,
      very little is known about this process in infancy. Recent research in infants
      has revealed discrepancies in the cortical location of voice-selective
      activation, as well as the age of onset of this response. The current study used
      functional near-infrared spectroscopy (fNIRS) to further investigate voice
      processing in awake 4-7-month-old infants. In listening to voice and non-voice
      sounds, there was robust and widespread activation in bilateral temporal cortex.
      Further, voice-selective regions of the bilateral anterior temporal cortex
      evidenced a steady increase in voice selective activation (voice > non-voice
      activation) over 4-7 months of age. These findings support a growing body of
      evidence that the emergence of cerebral specialization for human voice sounds
      evolves over the first 6 months of age. 

PMID- 21950956
TI  - The particle size effect on the oxygen reduction reaction activity of Pt
      catalysts: influence of electrolyte and relation to single crystal models.
AB  - The influence of particle size on the oxygen reduction reaction (ORR) activity of
      Pt was examined in three different electrolytes: two acidic solutions, with
      varying anionic adsorption strength (HClO(4) < H(2)SO(4)); and an alkaline
      solution (KOH). The experiments show that the absolute ORR rate is dependent on
      the supporting electrolyte; however, the relationship between activity and
      particle size is rather independent of the supporting electrolyte. The specific
      activity (SA) toward the ORR rapidly decreases in the order of polycrystalline Pt
      > unsupported Pt black particles (~30 nm) > high surface area (HSA) carbon
      supported Pt nanoparticle catalysts (of various size between 1 and 5 nm). In
      contrast to previous work, it is highlighted that the difference in SA between
      the individual HSA carbon supported catalysts (1 to 5 nm) is rather trivial and
      that the main challenge is to understand the significant differences in SA
      between the polycrystalline Pt, unsupported Pt particles, and HSA carbon
      supported Pt catalysts. Finally, a comparison between measured and modeled
      activities (based on the distribution of surface planes and their SAs) for
      different particle sizes indicates that such simple models do not capture all
      aspects of the behavior of HSA carbon supported catalysts.

PMID- 21950957
TI  - Bitoric rigid gas permeable contact lens fitting for the management of a corneal
      scar caused by herpes zoster ophthalmicus.
AB  - Empirical fitting of a bitoric rigid gas permeable contact lens for the
      management of a scarred irregular cornea caused by herpes zoster ophthalmicus is
      described. Two corneal scars, which affect the pupil axis, caused an irregular
      cornea and produced low visual acuity and anisometropia. Two contact lenses were
      necessary to complete the fitting. Visual acuity improved from 0.2 to 1.0. The
      rigid gas permeable lenses can be a good alternative in the management of
      patients with irregular corneas caused by herpes zoster ophthalmicus.

PMID- 21950958
TI  - Plasma myeloperoxidase level and peripheral arterial disease.
AB  - BACKGROUND: Myeloperoxidase (MPO) is involved in a multitude of inflammatory
      processes involving oxidative modification of soluble components and cellular
      surfaces. Thus, MPO plays a key role in promoting atherosclerosis via oxidative
      stress by modification of both high- and low-density lipoprotein and production
      of other bioactive molecules. A polymorphism (MPO 463G>A, rs2333227) results in
      different expression rates of MPO. We aimed to assess whether MPO could be of
      clinical use as a risk marker for vascular disease in a high-risk group. MATERIAL
      AND METHODS: Plasma MPO levels of 406 patients suffering from peripheral arterial
      disease (PAD) were measured on an Abbott Architect i2000sr and grouped into
      patients with high (>115 ng/mL) and low (< 115 ng/mL) MPO levels. Genotyping of
      rs2333227 was performed on an ABI TaqMan 7900HT RT-PCR thermocycler. RESULTS: The
      relative risk of major adverse cardiovascular events (MACE) for patients with
      high plasma MPO is 1.2 (95%CI: 1.038-1.377, P < 0.05), initial event-free periods
      in male patients are significantly longer in patients with MPO <115 ng/mL (mean =
      875 days compared with mean = 734 days, P < 0.05) In smokers, an increased hazard
      ratio was computed for patients with high MPO levels (HR = 3.127, 95%CI: 1.258
      7.772, P < 0.05). Effects of MPO [-463A] allele on initial MACE-free intervals
      did not persist after multivariate analysis. CONCLUSIONS: Hence, we suggest
      consideration of plasma MPO for risk stratification of MACE in patients with PAD.
      In contrast, MPO-463G>A is not an independent risk factor for MACE in patients
      suffering from PAD.

PMID- 21950959
TI  - Current perspectives of insulin resistance and polycystic ovary syndrome.
AB  - AIMS: To review the relationship between insulin resistance and polycystic ovary
      syndrome. METHODS: A literature review. RESULTS: Insulin resistance likely plays
      a central pathogenic role in polycystic ovary syndrome and may explain the
      pleiotropic presentation and involvement of multiple organ systems. Insulin
      resistance in the skeletal muscle of women with polycystic ovary syndrome
      involves both intrinsic and acquired defects in insulin signalling. The cellular
      insulin resistance in polycystic ovary syndrome has been further shown to involve
      a novel post-binding defect in insulin signal transduction. Treatment of insulin
      resistance through lifestyle therapy or with a diabetes drug has become
      mainstream therapy in women with polycystic ovary syndrome. However, effects with
      current pharmacologic treatment with metformin tend to be modest, with limited
      benefit as an agent to treat infertility. Insulin resistance contributes to
      increased risk for pregnancy complications, diabetes and cardiovascular disease
      risk profile in polycystic ovary syndrome, which is further exacerbated by
      obesity. While numerous studies demonstrate increased prevalence of
      cardiovascular disease risk factors in women with polycystic ovary syndrome,
      there are limited data showing that women with polycystic ovary syndrome are at
      increased risk for cardiovascular disease events. CONCLUSIONS: Insulin resistance
      is linked to polycystic ovary syndrome. Further study of lifestyle and
      pharmacologic interventions that reduce insulin resistance, such as metformin,
      are needed to demonstrate that they are effective in reducing the risk of
      diabetes, endometrial abnormalities and cardiovascular disease events in women
      with polycystic ovary syndrome.

PMID- 21950960
TI  - Fourier transform infrared spectroscopy and theoretical study of dimethylamine
      dimer in the gas phase.
AB  - Dimethylamine (DMA) has been studied by gas-phase Fourier transform infrared
      (FTIR) spectroscopy. We have identified a spectral transition that is assigned to
      the DMA dimer. The IR spectra of the dimer in the gas phase are obtained by
      spectral subtraction of spectra recorded at different pressures. The enthalpy of
      hydrogen bond formation was obtained for the DMA dimer by temperature-dependence
      measurements. We complement the experimental results with ab initio and
      anharmonic local mode model calculations of monomer and dimer. Compared to the
      monomer, our calculations show that in the dimer the N-H bond is elongated, and
      the NH-stretching fundamental shifts to a lower wavenumber. More importantly, the
      weak NH-stretching fundamental transition has a pronounced intensity increase
      upon complexation. However, the first NH-stretching overtone transition is not
      favored by the same intensity enhancement, and we do not observe the first NH
      stretching overtone of the dimer. On the basis of the measured and calculated
      intensity of the NH-stretching transition of the dimer, the equilibrium constant
      for dimerization at room temperature was determined.

PMID- 21950961
TI  - Cyclosporin variably and inconsistently reduces infarct size in experimental
      models of reperfused myocardial infarction: a systematic review and meta
      analysis.
AB  - Cyclosporin is an immunosuppressant that has recently been proposed as a
      treatment to prevent reperfusion injury in acute myocardial infarction (MI). We
      aimed to determine the overall efficacy of cyclosporin in experimental studies of
      acute reperfused MI. We conducted a systematic review and stratified meta
      analysis of published studies describing the efficacy of cyclosporin in
      experimental models of acute reperfused MI. We included all in vivo publications
      of cyclosporin where infarct size was measured. A literature search identified 29
      potential studies of which 20 fulfilled the eligibility criteria. In these
      studies (involving four species of animals), cyclosporin reduced myocardial
      infarct size by a standardized mean (95% confidence interval) difference of -1.60
      (-2.17, -1.03) compared with controls. Cyclosporin failed to demonstrate a
      convincing benefit in studies involving pigs. Despite this observation, the
      overall efficacy of cyclosporin did not differ across species (P= 0.358). The
      dose of cyclosporin given did not affect final infarct size (P= 0.203). Funnel
      plots of these data suggested heterogeneity among the studies. Cyclosporin had
      variable effects on infarct size compared with placebo. Cyclosporin had no effect
      on myocardial infarct size in swine, raising a question over the potential
      cardioprotective effects of cyclosporin in man.

PMID- 21950963
TI  - Birth of healthy twins after intracytoplasmic sperm injection using ejaculated
      immotile spermatozoa from a patient with Kartagener's syndrome.
AB  - This case report demonstrates a successful pregnancy after ICSI combined with
      hypo-osmotic swelling test in a couple with Kartagener's syndrome with complete
      immotile ejaculated spermatozoa. Our result suggests that even for complete
      immotile spermatozoa, the use of hypo-osmotic swelling test is a good alternative
      to identify viable spermatozoa. When associated with ICSI, it can be a valuable
      tool to get fertilisation and pregnancy.

PMID- 21950962
TI  - SYBR green as a fluorescent probe to evaluate the biofilm physiological state of
      Staphylococcus epidermidis, using flow cytometry.
AB  - Staphylococcus epidermidis biofilms with different proportions of viable but
      nonculturable bacteria were used to show that SYBR green (SYBR) may be used as a
      probe to evaluate the bacterial physiological state using flow cytometry.
      Biofilms grown in excess glucose presented significantly higher proportions of
      dormant bacteria than biofilms grown in excess glucose with buffered pH
      conditions or with exponential-phase planktonic cultures. Bacteria obtained from
      biofilms with high or low proportions of viable but nonculturable cells were
      further cultured in broth medium and stained with SYBR at different time points.
      An association between bacterial growth and SYBR staining intensity was observed.
      In addition, bacteria presenting higher SYBR fluorescence intensity also stained
      more intensely with cyanoditolyl tetrazolium chloride, used as a probe to
      evaluate cellular metabolism. Accordingly, planktonic bacteria treated with
      rifampicin, an inhibitor of bacterial RNA transcription, presented lower SYBR and
      cyanoditolyl tetrazolium chloride staining intensity than nontreated bacteria.
      Overall, our results indicate that SYBR, in addition to being used as a component
      of LIVE/DEAD stain, may also be used as a probe to evaluate the physiological
      state of S. epidermidis cells.

PMID- 21950964
TI  - Autophagosomes accumulation is associated with beta-amyloid deposits and
      secondary damage in the thalamus after focal cortical infarction in hypertensive
      rats.
AB  - Focal cerebral cortical infarction after distal middle cerebral artery occlusion
      causes beta-amyloid deposition and secondary neuronal degeneration in the
      ipsilateral ventroposterior nucleus of the thalamus. Several studies suggest that
      autophagy is an active pathway for beta-amyloid peptide generation. This study
      aimed to investigate the role of autophagy in thalamic beta-amyloid deposition
      and neuronal degeneration after cerebral cortical infarction in hypertensive
      rats. At 7 and 14days after middle cerebral artery occlusion, neuronal death and
      beta-amyloid deposits were evident in the ipsilateral ventroposterior nucleus,
      and the activity of beta-site amyloid precursor protein (APP)-cleaving enzyme 1,
      required for beta-amyloid peptide generation, was elevated in the thalamus. In
      correlation, both the number of cells showing punctate microtubule-associated
      protein 1A light chain 3 fluorescence and levels of light chain 3-II protein, an
      autophagosome marker, were markedly increased. Notably, most of the cells that
      over-expressed beta-site APP-cleaving enzyme 1 displayed punctate light chain 3
      staining. Furthermore, the inhibition of autophagy with 3-methyladenine
      significantly reduced the thalamic neuronal damage, beta-amyloid deposits, and
      beta-site APP-cleaving enzyme 1 activity. These results suggest that
      autophagosomes accumulate within thalamic cells after cerebral cortical
      infarction, which is associated with thalamic beta-amyloid deposition and
      secondary neuronal degeneration via elevation of beta-site APP-cleaving enzyme 1
      level.

PMID- 21950965
TI  - Two cases of congenital aplasia cutis with dermal melanocytosis.

PMID- 21950966
TI  - A comparison of the thermal adaptability of people accustomed to air-conditioned
      environments and naturally ventilated environments.
AB  - It has been reported previously that people who are acclimated to naturally
      ventilated (NV) environments respond to hot and warm environments differently
      than people who are acclimated to air-conditioned (AC) environments. However, it
      is not clear whether physiological acclimatization contributes to this
      discrepancy. To study whether living and working in NV or AC environments for
      long periods of time can lead to different types of physiological
      acclimatization, and whether physiological acclimatization has an important
      influence on people's responses of thermal comfort, measurements of physiological
      reactions (including skin temperature, sweat rate, heart rate variability, and
      heat stress protein 70) and thermal comfort responses were conducted in a 'heat
      shock' environment (climate chamber) with 20 people (10 in the NV group and 10 in
      the AC group). The results showed that the NV group had a significantly stronger
      capacity for physiological regulation to the heat shock than the AC group. In
      other words, the NV group did not feel as hot and uncomfortable as the AC group
      did. These results strongly indicate that living and working in indoor thermal
      environments for long periods of time affects people's physiological
      acclimatization. Also, it appears that long-term exposure to stable AC
      environments may weaken people's thermal adaptability. PRACTICAL IMPLICATIONS:
      This study examined the psychological and physiological differences of thermal
      adaptability of people used to air-conditioned environments and naturally
      ventilated environments. The results suggested that long-term exposure to stable
      air-conditioned environments may weaken people's thermal adaptability. Therefore,
      it might be advantageous for people to spend less time in static air-conditioned
      environments; this is not only because of its possible deleterious impact on
      people's physiological adaptability, but also because the air-conditioners' high
      energy consumption will contribute to the effects of global warming.

PMID- 21950967
TI  - Adsorption kinetics of ultrathin polymer films in the melt probed by dielectric
      spectroscopy and second-harmonic generation.
AB  - We studied the adsorption kinetics of supported ultrathin films of dye-labeled
      polystyrene (l-PS) by combining dielectric spectroscopy (DS) and the interface
      specific nonlinear optical second harmonic generation (SHG) technique. While DS
      is sensitive to the fraction of mobile dye moieties (chromophores), the SHG
      signal probes their anisotropic orientation. Time-resolved measurements were
      performed above the glass transition temperature on two different sample
      geometries. In one configuration, the l-PS layer is placed in contact with the
      aluminum surface, while in the other one, the deposition is done on a strongly
      adsorbed layer of neat PS. From the time dependence of the dielectric strength
      and SHG signal of the l-PS layer in contact with the metal, we detected two
      different kinetics regimes. We interpret these regimes in terms of the interplay
      between adsorption and orientation of the adsorbing labeling moieties. At early
      times, dye moieties get adsorbed adopting an orientation parallel to the surface.
      When adsorption proceeds to completeness, the kinetics slows down and the dye
      moieties progressively orient normal to the surface. Conversely, when the layer
      of l-PS layer is deposited on the strongly adsorbed layer of neat PS, both the
      dielectric strength and the SHG signal do not show any variation with time. This
      means that no adsorption takes place.

PMID- 21950968
TI  - Role of ethylene in alleviation of cadmium-induced photosynthetic capacity
      inhibition by sulphur in mustard.
AB  - Sulphur (S) assimilation leads to the formation of glutathione (GSH) and
      alleviation of cadmium (Cd) stress. GSH is synthesized from its immediate
      metabolite cysteine, which also serves as a metabolite for ethylene formation
      through S-adenosyl methionine. To assess the role of ethylene in S-induced
      alleviation of Cd stress on photosynthesis, the effects of S or ethephon
      (ethylene source) on GSH and ethylene were examined in mustard (Brassica juncea
      L. cv. Varuna). Sufficient-S at 100 mg S kg(-1)  soil alleviated Cd-induced
      photosynthetic inhibition more than excess-S (200 mg S kg(-1)  soil) via ethylene
      by increased GSH. Under Cd stress, plants were less sensitive to ethylene,
      despite high ethylene evolution, and showed photosynthetic inhibition. Ethylene
      sensitivity of plants increased with ethephon or sufficient-S, triggering the
      induction of an antioxidant system, and leading to increased photosynthesis even
      under Cd stress. The effects of ethephon and S under Cd stress were similar. The
      effects of S were reversed by ethylene biosynthesis inhibitor,
      aminoethoxyvinylglycine (AVG), suggesting that ethylene plays an important role
      in S-induced alleviation of Cd stress on photosynthesis.

PMID- 21950969
TI  - Is there any sense in the Palisade endings of eye muscles?
AB  - Palisade endings (PEs), which are unique to the eye muscles, are associated with
      multiply innervated muscle fibers. They lie at the myotendinous junctions and
      form a cap around the muscle fiber tip. They are found in all animals
      investigated so far, but their function is not known. Recently, we demonstrated
      that cell bodies of PEs and tendon organs lie around the periphery of the
      oculomotor nucleus in the C- and S-groups. A morphological analysis of these
      peripheral neurons revealed the existence of different populations within the C
      group. We propose that a small group of round or spindle-shaped cells gives rise
      to PEs, and another group of multipolar neurons provide the multiple motor
      endings. If PEs have a sensory function, then their cell body location close to
      motor neurons would be in an ideal location to control tension in extraocular
      muscles; in the case of the C-group, its proximity to the preganglionic neurons
      of the Edinger-Westphal nucleus would permit its participation in the near
      response. Despite their unusual properties, PEs may have a sensory function.

PMID- 21950971
TI  - The nonlinearity of passive extraocular muscles.
AB  - Passive extraocular muscles (EOMs), like most biological tissues, are
      hyperelastic, that is, their stiffness increases as they are stretched. It has
      always been assumed, and in a few occasions argued, that this is their only
      nonlinearity and that it can be ignored in central gaze. However, using novel
      measurement techniques in anesthetized paralyzed monkeys, we have recently
      demonstrated that EOMs are characterized by another prominent nonlinearity: the
      forces induced by sequences of stretches do not sum. Thus, superposition, a
      central tenet of linear and quasi-linear models, does not hold in passive EOMs.
      Here, we outline the implications of this finding, especially in light of the
      common assumption that it is easier for the brain to control a linear than a
      nonlinear plant. We argue against this common belief: the specific nonlinearity
      of passive EOMs may actually make it easier for the brain to control the plant
      than if muscles were linear.

PMID- 21950970
TI  - Expanding repertoire in the oculomotor periphery: selective compartmental
      function in rectus extraocular muscles.
AB  - Since connective tissue pulleys implement Listing's law by systematically
      changing rectus extraocular muscle (EOM) pulling directions, non-Listing's law
      gaze dependence of the vestibulo-ocular reflex is currently inexplicable.
      Differential activation of compartments within rectus EOMs may endow the ocular
      motor system with more behavioral diversity than previously supposed. Innervation
      to horizontal, but not vertical, rectus EOMs of mammals is segregated into
      superior and inferior compartments. Magnetic resonance imaging in normal subjects
      demonstrates contractile changes in the lateral rectus (LR) inferior, but not
      superior, compartment during ocular counter-rolling (OCR) induced by head tilt.
      In human orbits ipsilesional to unilateral superior oblique palsy, neither LR
      compartment exhibits contractile change during head tilt, although the inferior
      compartment contracts normally in contralesional orbits. This suggests that
      differential compartmental LR contraction assists normal OCR. Computational
      simulation suggests that differential compartmental action in horizontal rectus
      EOMs could achieve more force than required by vertical fusional vergence.

PMID- 21950972
TI  - Factors contributing to failure of neuromuscular transmission in myasthenia
      gravis and the special case of the extraocular muscles.
AB  - Acetylcholine receptors (AchRs) and Na(+)  channels (NaChs) are concentrated on
      neuromuscular junction (NMJ) postsynaptic folds; both are depleted in myasthenia
      gravis (MG), reducing the safety factor (SF) for neuromuscular transmission,
      especially in extraocular muscles (EOM). Studies of human myasthenic nerve-muscle
      preparations indicate that loss of endplate AChRs accounts for 59%, and NaChs for
      40%, of SF reduction. Rodent models of MG indicate that NaChs and AChRs losses
      are due to complement-mediated destruction of postsynaptic folding. Saccades in
      MG show stereotyped, conjugate initial components, similar to normal but
      different from early disconjugacy with ocular nerve palsies. Loss of AChRs,
      NaChs, and postsynaptic folding all contribute to SF reduction in MG. EOM seem
      more susceptible to MG because of poor postsynaptic folding, lower baseline SF,
      and lower levels of intrinsic complement inhibitors. Initial conjugacy of
      saccades in MG reflects selective sparing of neuromuscular transmission of fast,
      pale global fibers, which have better developed postsynaptic folding.

PMID- 21950973
TI  - Three-dimensional kinematics of saccadic eye movements in humans: is the "half
      angle rule" obeyed?
AB  - The "half-angle rule" must be satisfied for Listing's law to be obeyed during
      saccades: the eye velocity axis must tilt away from Listing's plane by half the
      angle of eye position eccentricity from primary position. We aimed to determine
      if this rule is satisfied during saccades. Horizontal and vertical saccades were
      recorded using the search coil technique, at different elevations and azimuths,
      in five normal humans. In all, eye positions were located on a twisted rather
      than planar surface. The mean tilt-angle coefficients (TACs; ratio of angle of
      eye velocity axis tilt to angle of eye position eccentricity) were 0.57 and 0.34
      for horizontal and vertical saccades, respectively. TACs were significantly lower
      for vertical saccades. Thus, Listing's law is not perfectly obeyed during
      saccades. We suggest that the discrepancy in horizontal and vertical TACs causes
      eye positions to lie on a twisted rather than planar surface in three-dimensional
      space.

PMID- 21950974
TI  - Circuit dynamics of the superior colliculus revealed by in vitro voltage imaging.
AB  - The superior colliculus (SC) is well known for its involvement in the conversion
      of sensory stimuli into motor commands. This sensorimotor integration is made
      possible by the collective activity of multiple neuronal connections throughout
      the SC. Still, the majority of SC research focuses on in vivo extracellular
      recordings of behaving monkeys or in vitro patch-clamp recordings from lower
      mammals. Here, we discuss the results of an in vitro voltage-imaging technique in
      which population activity across the rodent SC circuitry was visualized to bridge
      the gap between single-cell recordings and whole-animal behavior. The high
      temporal and spatial resolution of the voltage-imaging technique allowed us to
      visualize patterns of activity following stimulation at discrete laminae.
      Stimulation within either the superficial or intermediate layer showed
      recruitment of disparate SC circuitry. These results provide insight into the
      circuit dynamics and neuronal populations that underlie behavior.

PMID- 21950975
TI  - Do brainstem omnipause neurons terminate saccades?
AB  - Saccade-generating burst neurons (BN) are inhibited by omnipause neurons (OPN),
      except during saccades. OPN activity pauses before saccade onset and resumes at
      the saccade end. Microstimulation of OPN stops saccades in mid-flight, which
      shows that OPN can end saccades. However, OPN pause duration does not correlate
      well with saccade duration, and saccades are normometric after OPN lesions. We
      tested whether OPN were responsible for stopping saccades both in late-onset Tay
      Sachs, which causes premature saccadic termination, and in individuals with
      cerebellar hypermetria. We studied gaze shifts between two targets at different
      distances aligned on one eye, which consist of a disjunctive saccade followed by
      vergence. High-frequency conjugate oscillations during the vergence movements
      that followed saccades were present in all subjects studied, indicating OPN
      silence. Thus, mechanisms other than OPN discharge (e.g., cerebellar caudal
      fastigial nucleus-promoting inhibitory BN discharge) must contribute to saccade
      termination.

PMID- 21950976
TI  - The effects of ion channel blockers validate the conductance-based model of
      saccadic oscillations.
AB  - Conductance-based models of reciprocally inhibiting burst neurons suggest that
      intrinsic membrane properties and postinhibitory rebound (PIR) determine the
      amplitude and frequency of saccadic oscillations. Reduction of the low-threshold
      calcium currents (I(T)) in the model decreased the amplitude but increased the
      frequency of the simulated oscillations. Combined reduction of hyperpolarization
      activated cation current (I(h)) and I(T) in the model abolished the simulated
      oscillations. We measured the effects of a selective blocker of I(T)
      (ethosuximide) in healthy subjects on the amplitude and frequency of saccadic
      oscillations evoked by eye closure and of a nonselective blocker of I(h) and I(T)
      (propronolol) in a patient with microsaccadic oscillation and limb tremor
      syndrome (mSOLT). Ethosuximide significantly reduced the amplitude but increased
      the frequency of the saccadic oscillations during eye closure in healthy
      subjects. Propranolol abolished saccadic oscillations in the mSOLT patient. These
      results support the hypothetical role of postinhibitory rebound, I(h), and I(T) ,
      in generation of saccadic oscillations and determining their kinematic
      properties.

PMID- 21950977
TI  - Influence of orbital eye position on vertical saccades in progressive
      supranuclear palsy.
AB  - Disturbance of vertical saccades is a cardinal feature of progressive
      supranuclear palsy (PSP). We investigated whether the amplitude and peak velocity
      (PV) of saccades are affected by the orbital position from which movements start
      in PSP patients and age-matched control subjects. Subjects made vertical saccades
      in response to +/-5 degrees  vertical target jumps with their heads in one of
      three positions: head "center," head pitched forward ~15 degrees , and head
      pitched back ~15 degrees . All patients showed some effect of starting eye
      position, whether beginning in the upward or downward field of gaze, on saccade
      amplitude, PV, and net range of movement. Generally, reduction of amplitude and
      PV were commensurate and bidirectional in the affected hemifield of gaze. Such
      findings are unlikely to be because of orbital factors and could be explained by
      varying degrees of involvement of rostral midbrain nuclei in the pathological
      process.

PMID- 21950978
TI  - Effects of unilateral midbrain lesions on gaze (eye and head) movements.
AB  - The rostral midbrain, especially the rostral interstitial nucleus of the medial
      longitudinal fasciculus (RIMLF) and the interstitial nucleus of Cajal (INC),
      plays an important role in the control of eye movements. Although the effect of
      midbrain lesions on eye movements is well investigated, little is known about its
      effect on head movements. In this study, we measured eye and head (gaze)
      movements in five patients with unilateral, acute midbrain lesions and nine
      healthy controls. In all patients, vertical eye velocity was reduced as a result
      of the lesion compared to healthy subjects, whereas peak head velocity was not
      affected. Further, most patients displayed an increased contralesional torsion in
      peripheral head positions, independently of whether they presented a head tilt in
      the straight-ahead position or not. Our results indicate that midbrain lesions
      affect the control of eye and head differently and independently.

PMID- 21950979
TI  - Vertical alignment in monkeys with unilateral IV section: effects of prolonged
      monocular patching and trigeminal deafferentation.
AB  - We investigated monocular viewing and trigeminal (V) deafferentation on the
      vertical deviation (VD) in monkeys following intracranial IV section. Two monkeys
      wore a patch for four to six weeks, one over the paretic eye and the other over
      the normal eye following IV section. Two other monkeys had combined IV and V
      section with the paretic eye patched postlesion. In monkeys with IV section
      alone, the VD lessened within the first week postlesion but then increased
      gradually with the same eye still patched. Thus binocular viewing was unnecessary
      for the later VD increase. With combined IV and V section, the VD also
      transiently lessened postlesion. We have proposed that the decrease in VD after
      IV section is adaptive, driven by an error signal using ocular proprioception and
      efference copy. Since V section did not eliminate the early decrease in VD, we
      suggest some orbital afference is transmitted centrally via other cranial nerves.
      However, the later increase in VD suggests either that the proprioceptive effect
      cannot be sustained or that mechanical changes supervene to increase the VD.

PMID- 21950980
TI  - Cells in the supraoculomotor area in monkeys with strabismus show activity
      related to the strabismus angle.
AB  - We have earlier shown that monkeys reared with daily alternating monocular
      occlusion for the first few months of life develop large horizontal strabismus,
      A/V patterns, dissociated vertical deviation (DVD), and dissociated horizontal
      deviation (DHD). Here, we present results from neurophysiological experiments
      that show that neuronal activity of cells within the supraoculomotor area (SOA)
      of juvenile strabismic monkeys is correlated with the angle of strabismus. There
      was no modulation of SOA cell activity with conjugate eye position as tested
      during horizontal smooth pursuit. Comparison of SOA population activity in these
      strabismic animals and normal monkeys (described in the literature) suggests that
      both vergence (misalignment in the case of the strabismic animals) thresholds and
      vergence position sensitivities are different in the strabismic animals compared
      to the normals. Our data suggest that activity within the SOA cells is important
      in determining the state of horizontal strabismus possibly by altering vergence
      tone in extraocular muscle.

PMID- 21950982
TI  - Neural substrate for suppression of omnipause neurons at the onset of saccades.
AB  - The saccade trigger signal was proposed by D.A. Robinson, but neural substrates
      for triggering saccades by inhibiting omnipause neuron (OPN) activity still
      remain controversial. We investigated tectal inputs to OPNs by recording
      intracellular potentials from OPNs and inhibitory burst neurons (IBNs) and
      searched for interneurons to inhibit OPNs in the brainstem of anesthetized cats.
      IBNs received monosynaptic excitation from the contralateral caudal superior
      colliculus (SC) and disynaptic inhibition via contralateral IBNs from the
      ipsilateral caudal SC, whereas IBNs received disynaptic inhibition from the
      rostral SC. The latter disynaptic inhibition was mediated by OPNs, since OPNs
      received monosynaptic excitation from the rostral SC and projected to IBNs. In
      contrast, OPNs received disynaptic inhibition from the caudal SC. This disynaptic
      inhibition from the caudal SC was mediated to OPNs by IBNs. These findings
      suggested possible roles of IBNs for triggering and maintaining saccades by
      actively inhibiting the tonic activity of OPNs.

PMID- 21950981
TI  - Sources of calretinin inputs to motoneurons of extraocular muscles involved in
      upgaze.
AB  - Recent monkey studies showed that motoneurons of the oculomotor nucleus involved
      in upward eye movements receive a selective input from afferents containing
      calretinin (CR). Here, we investigated the sources of these CR-positive
      afferents. After injections of tract-tracers into the oculomotor nucleus (nIII)
      of two monkeys, the retrograde labeling was combined with CR-immunofluorescence
      in frozen brainstem sections. Three sources of CR inputs to nIII were found: the
      rostral interstitial nucleus of the medial longitudinal fascicle (RIMLF), the
      interstitial nucleus of Cajal, and the y-group. CR is not present in all premotor
      upward-moving pathways. The excitatory secondary vestibulo-ocular neurons in the
      magnocellular part of the medial vestibular nuclei contained nonphosphorylated
      neurofilaments, but no CR, and they received a strong supply of large CR-positive
      boutons. In conclusion, the present study presents evidence that only specific
      premotor pathways for upward eye movements--excitatory upgaze pathways--contain
      CR, but not the up vestibulo-ocular reflex pathways. This property may help to
      differentiate between premotor up- and downgaze pathways in correlative clinico
      anatomical studies in humans.

PMID- 21950983
TI  - Triggering mechanisms in microsaccade and saccade generation: a novel proposal.
AB  - Saccades are rapid eye movements that change the line of sight between successive
      points of fixation. Even as we attempt to fixate our gaze precisely, small rapid
      eye movements called microsaccades interrupt fixation one or two times each
      second. Although the neural pathway controlling saccade generation is well
      understood, the specific mechanism for triggering microsaccades is unknown. Here,
      we review the evidence suggesting that microsaccades and saccades are generated
      by the same neural pathway. We also discuss current models of how the saccadic
      system produces microsaccades. Finally, we propose a new mechanism for triggering
      both microsaccades and saccades, based on a circuit formed by omnipause and long
      lead burst neurons and driven by activity in the superior colliculus. Our model
      differs from previous proposals in that it does not require superior colliculus
      activity to surpass a particular threshold to trigger microsaccades and saccades.
      Rather, we propose that the reciprocal inhibition between omnipause and long-lead
      burst neurons gates each microsaccadic or saccadic event, triggering the eye
      movement whenever the activity in the long-lead burst neurons overcomes the
      inhibition from the omnipause neurons.

PMID- 21950984
TI  - Memory-based smooth pursuit: neuronal mechanisms and preliminary results of
      clinical application.
AB  - Using a memory-based smooth-pursuit task, macaque monkeys were trained to pursue
      (i.e., go) or not pursue (i.e., no-go), a cued direction, based on the memory of
      visual motion-direction and a go/no-go instruction. Task-related neuronal
      activity was examined in the supplementary eye fields, caudal frontal eye fields,
      cerebellar floccular region, dorsal vermis lobules VI-VII, and caudal fastigial
      nuclei. Different cerebral and cerebellar areas carried distinctly different
      signals during memory-based smooth pursuit. Chemical inactivation of these areas
      produced effects consistent with the differences in signals represented in each
      area. This task was applied to patients with idiopathic Parkinson's disease (PD),
      because impaired visual working memory has been reported during cognitive tasks
      in PD. None of the PD patients tested exhibited impaired working memory of motion
      direction and/or go/no-go selection, but they had difficulty in preparing for and
      executing smooth-pursuit eye movements, suggesting a selective motor-related
      disturbance in Parkinson's disease.

PMID- 21950985
TI  - Clinical, electrophysiological, and MRI findings in patients with cerebellar
      ataxia and a bilaterally pathological head-impulse test.
AB  - A significant number of patients with bilateral vestibulopathy suffer from
      cerebellar ataxia and central vestibular symptoms and vice versa. We examined 31
      patients presenting with the combination of gait and stance ataxia, cerebellar
      ocular motor signs, and a bilaterally pathological head-impulse test (HIT). Tests
      included neuro-orthoptical examination, electromyography and neurography, caloric
      irrigation, pure-tone audiogram, vestibular-evoked myogenic potentials, and
      volumetric magnetic resonance imaging (MRI). Only 17 of 31 patients had a
      pathological caloric irrigation. Twenty-three patients had evidence of
      polyneuropathy (predominantly mixed sensorimotor involving axonal loss and
      demyelination) and twenty of hypoacusis (1 unilateral and 19 bilateral). Voxel
      based morphometry comparing local gray matter brain volume between patients and
      controls revealed cerebellar atrophy involving both the vermis and the
      hemispheres. We conclude that there is a clinically relevant combination of
      cerebellar ataxia with cerebellar atrophy, bilaterally pathological HIT,
      polyneuropathy, and hypoacusis. This multisensory syndrome is most likely caused
      by a neurodegenerative disorder affecting different systems, leading to severe
      impairment of affected patients.

PMID- 21950986
TI  - Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS): a review
      of the clinical features and video-oculographic diagnosis.
AB  - The association of bilateral vestibulopathy with cerebellar ataxia was first
      reported in 1991 and delineated as a distinct syndrome with a characteristic and
      measurable clinical sign--an absent visually enhanced vestibulo-ocular reflex--in
      2004. We reviewed 27 patients with this syndrome and show that a non-length
      dependent sensory deficit with absent sensory nerve action potentials is an
      integral component of this syndrome, which we now call "cerebellar ataxia with
      neuropathy and bilateral vestibular areflexia syndrome" (CANVAS). All patients
      had brain MRI and 22/27 had evidence of cerebellar atrophy involving anterior and
      dorsal vermis, as well as the hemispheric crus I. Brain and temporal bone
      pathology in one patient showed marked loss of Purkinje cells and of vestibular,
      trigeminal, and facial ganglion cells, but not of spiral ganglion cells. There
      are two sets of sibling pairs, suggesting CANVAS is a late-onset recessive
      disorder. The characteristic clinical sign-the visual vestibulo-ocular reflex
      deficit-can be demonstrated and measured clinically using video-oculography.

PMID- 21950987
TI  - Fast versus slow: different saccadic behavior in cerebellar ataxias.
AB  - Spinocerebellar ataxia type 2 (SCA2) is a genetic neurodegenerative disorder
      primarily characterized by involvement of the brainstem and cerebellum, basal
      ganglia, spinal cord, cerebral cortex, but white matter is also involved. In late
      onset cerebellar ataxia (LOCA), the cerebellum is mainly involved, as
      demonstrated by clinical and neuroradiological findings. These neurodegenerative
      diseases are often associated with progressive abnormalities in eye movement
      control, particularly saccadic changes. We recorded saccadic eye movements in
      eight SCA2 patients and 10 LOCA patients. Here, we suggest that abnormalities in
      saccadic parameters differ in the two groups of patients according to specific
      anatomical substrates. The different saccadic behavior observed in these two
      clinically distinct degenerative cerebellar diseases offers the opportunity to
      simplify some general mechanisms of saccadic motor control. Like his mentor Fred
      Plum, John Leigh strongly encouraged younger neuroscientists to tackle
      neurological problems by investigating "pathological physiology." With this
      teaching in mind, we studied patients with rare neurometabolic and
      neurodegenerative diseases.

PMID- 21950988
TI  - Critical role of cerebellar fastigial nucleus in programming sequences of
      saccades.
AB  - The cerebellum plays an important role in programming accurate saccades.
      Cerebellar lesions affecting the ocular motor region of the fastigial nucleus
      (FOR) cause saccadic hypermetria; however, if a second target is presented before
      a saccade can be initiated (double-step paradigm), saccade hypermetria may be
      decreased. We tested the hypothesis that the cerebellum, especially FOR, plays a
      pivotal role in programming sequences of saccades. We studied patients with
      saccadic hypermetria because of either genetic cerebellar ataxia or surgical
      lesions affecting FOR and confirmed that the gain of initial saccades made to
      double-step stimuli was reduced compared with the gain of saccades to single
      target jumps. Based on measurements of the intersaccadic interval, we found that
      the ability to perform parallel processing of saccades was reduced or absent in
      all of our patients with cerebellar disease. Our results support the crucial role
      of the cerebellum, especially FOR, in programming sequences of saccades.

PMID- 21950989
TI  - The role of regularity and synchrony of cerebellar Purkinje cells for
      pathological nystagmus.
AB  - Previous theories assumed that the beneficial effect of the potassium channel
      blocker 4-aminopyridine (4-AP) for patients suffering from downbeat nystagmus
      (DBN) or episodic ataxia type 2 (EA2) is due to an increase of excitability of
      cerebellar Purkinje cells (PC). Recent experimental results using therapeutic
      doses of 4-AP with a mouse model of EA2 challenged the theory showing that 4-AP
      does not change the firing rate of PC but their regularity. Based on a
      mathematical model of the ocular motor and cerebellar circuitry, we show that
      changes in regularity have no effect without synchrony in PC firing. Together
      with synchronous firing, an increase in regularity may lead to a decrease in
      overall inhibition and may invert the inhibitory to an excitatory response due to
      imprinting, a novel effect of synchronized neural inhibition. Both effects are
      unlikely to be the causative mechanism for the success of 4-AP in treating
      cerebellar disorders.

PMID- 21950990
TI  - The role of prediction and anticipation on age-related effects on smooth pursuit
      eye movements.
AB  - Externally guided sensory-motor processes deteriorate with increasing age.
      Internally guided, for example, predictive, behavior usually helps to overcome
      sensory-motor delays. We studied whether predictive components of visuomotor
      transformation decline with age. We investigated smooth pursuit eye movements
      (SPEM) of 45 healthy subjects with paradigms of different degrees of
      predictability with respect to target motion onset, type (smoothed triangular,
      ramp stimulation), and direction by blanking the target at various intervals of
      the ramp stimulation. Using repetitive trials of SPEM stimulation, we could
      dissociate anticipatory and predictive components of extraretinal smooth pursuit
      behavior. The main results suggest that basic motor parameters decline with
      increasing age, whereas both anticipation and prediction of target motion did not
      change with age. We suggest that the elderly maintain their capability of using
      prediction in the immediate control of motor behavior, which might be a way to
      compensate for age-related delays in sensory-motor transformation, even in the
      absence of sensory signals.

PMID- 21950991
TI  - Spatial separation of visual and vestibular processing in the human hippocampal
      formation.
AB  - The hippocampal formation, that is, the hippocampus proper and the
      parahippocampal region, is essential for various aspects of memory and plays an
      important role in human navigation. Navigational cues can be provided by both the
      visual system (e.g., landmarks, optic flow) and the vestibular system (e.g.,
      estimation of direction during path integration). This study reviews anatomical,
      electrophysiological, and imaging data that support the view that vestibular
      input is primarily processed in the anterior part of the hippocampal formation,
      whereas visual cues are primarily integrated in the posterior part. In cases of
      reduced vestibular or visual input or excessive sensory stimulation, this
      hippocampal navigational network is reorganized. The separation of vestibular and
      visual information in the hippocampal formation has a twofold functional
      consequence: missing input from either system may be partially substituted for,
      and the task-dependent sensorial weight can be shifted to, the more reliable
      modality for navigation.

PMID- 21950992
TI  - Neural mechanisms for smooth pursuit in strabismus.
AB  - The visual and oculomotor systems of primates are immature at birth and sensitive
      to injury. If synergistic interactions between visual and oculomotor systems are
      compromised during the first months of life, disorders in eye alignment, gaze
      holding, and smooth pursuit (SP) follow. Here we consider some potential neural
      mechanisms supporting SP and associated vestibular ocular reflex (VOR) behavior
      in normal and strabismic monkeys. Experimental strabismus was created by prism
      goggle wearing or eye muscle surgery in rhesus monkeys (Macaca mulatta). SP and
      cancellation of the VOR were highly asymmetric in strabismic monkeys during
      monocular viewing conditions. Similar asymmetric SP and VOR cancellation could be
      produced in normal monkeys by delivering unilateral muscimol injections to the
      dorsolateral pontine nucleus (DLPN). We suggest that failure to develop balanced
      cortical-brainstem circuits in strabismus accounts for many of the components of
      infantile strabismus syndrome.

PMID- 21950993
TI  - Antisaccade generation is impaired after parietal lobe lesions.
AB  - Antisaccades are directed away from visual targets. Impaired antisaccade
      generation has been attributed to frontal lobe damage. We studied antisaccades in
      patients with unilateral focal parietal lobe lesions. Normal subjects (N = 10)
      instructed to make 10 degrees  antisaccades opposite to a 100-ms target flash 10
      degrees  to the right or left of center made antisaccades in 86.1% of trials.
      Patients (N = 13) made antisaccades contraversive to their lesions in 55.4% of
      trials and 50.5% of ipsiversive trials. In other trials, reflexive saccades
      occurred toward the target flash. Nine patients with imaged lesions overlapping
      in parietal lobe white matter showed subnormal antisaccade generation.
      Antisaccades provide a means of measuring voluntary saccade function of the
      parietal lobes independent of visual guidance. Impaired suppression of reflexive
      saccades and generation of antisaccades is attributed to disconnection of
      parietal lobe from frontal lobe ocular motor areas.

PMID- 21950994
TI  - Probing V5/MT excitability with transcranial magnetic stimulation following
      visual motion adaptation to random and coherent motion.
AB  - The response to stimulating the visual cortex with transcranial magnetic
      stimulation (TMS) depends on its initial activation state, for example, visual
      motion adaptation biases perceived TMS-induced phosphene characteristics (e.g.,
      color). We quantified this state dependence by assessing the probability of
      reporting a phosphene (P(lambda) ) with "threshold" TMS (i.e., the TMS intensity
      producing P(lambda) = 0.5 at baseline) following visual motion adaptation to a
      random dot motion display. Postadaptation, P(lambda) was increased, and this
      effect was confined to the adapted neuronal population. We then adapted subjects
      using a population of moving dots of fixed average motion direction with standard
      deviations (SD) ranging from 1 degrees  to 128 degrees  (SD fixed for a given
      trial). P(lambda) was significantly increased at all dot motion SDs except SD = 1
      degrees . Neuronal adaptation increases the susceptibility of the neuronal
      population to activation by threshold intensity TMS. Thus the process of neuronal
      adaption is not necessarily synonymous with a downmodulation of neuronal
      excitability.

PMID- 21950995
TI  - What Sherrington missed: the ubiquity of the neural integrator.
AB  - Despite its numerous illustrations unequivocally demonstrating the phenomenon, in
      Sherrington's Integrative Action of the Nervous System, he considered
      "integration" only in its spatial and coordinative aspects, and failed to notice
      time integration as an equally pervasive feature of all motor systems. First
      demonstrated in the oculomotor system by Robinson and others, in the vestibulo
      ocular reflex, and then as a necessary component of the oculomotor "final common
      path" (another Sherringtonian concept), integration is manifested at two further
      levels: in generating optokinetic responses and in the mechanism of saccadic
      decision. But integration is not a purely oculomotor phenomenon: behind it lie
      two fundamental motor principles. First, that the brain operates in terms of
      change, implying differentiation in sensory systems and integration in motor
      ones. Second, that the molecular physiology of muscle contraction means that
      remaining still requires not only continual expenditure of energy but also
      continual computational effort--a firm and precise integrator.

PMID- 21950996
TI  - Orientation adaptation of eye movement-related vestibular neurons due to
      prolonged head tilt.
AB  - Sixteen neurons, including vestibular-only (VO), eye-head velocity (EHV), and
      position-vestibular-pause (PVP) neurons sensitive to head tilt were recorded in
      the rostromedial and in superior vestibular nuclei. Projection of the otolith
      polarization vector to the horizontal plane (response vector orientation [RVO])
      was determined before and after prolonged head orientation in side-down position.
      The RVO of VO neurons shifted toward alignment with the axis of gravity when the
      head was in the position of adaptation. PVP neurons had similar changes in RVO.
      There were also changes in RVO in some EHV neurons, but generally in directions
      not related to gravity. Modeling studies have suggested that the tendency to
      align RVOs with gravity leads to tuning of gravity-dependent angular vestibular
      ocular reflex (aVOR) gain changes to the position of adaptation. Thus, coding of
      orientation in PVP neurons would contribute significantly to the gravity
      dependent adaptation of the aVOR.

PMID- 21950997
TI  - Anticipatory eye movements stabilize gaze during self-generated head movements.
AB  - Visual acuity and motion perception are degraded during head movements unless the
      eyes counter-rotate so as to stabilize the line of sight and the retinal image.
      The vestibulo-ocular reflex (VOR) is assumed to produce this ocular counter
      rotation. Consistent with this assumption, oscillopsia is a common complaint of
      patients with bilateral vestibular weakness. Shanidze et al. recently described
      compensatory eye movements in normal guinea pigs that appear to anticipate self
      generated head movements. These responses effectively stabilize gaze and occur
      independently of the vestibular system. These new findings suggest that the VOR
      stabilizes gaze during passive perturbations of the head in space, but
      anticipatory responses may supplement or even supplant the VOR during actively
      generated head movements. This report reviews these findings, potential
      neurophysiological mechanisms, and their potential application to human clinical
      treatment of patients with vestibular disease.

PMID- 21950998
TI  - A new device to assess static ocular torsion.
AB  - In clinical settings, static ocular torsion is assessed by taking a fundus
      photograph and measuring the angle between a horizontal line and the line
      connecting the fovea to the head of the optic nerve (centro-cecal axis rotation;
      CCAR). We developed and tested a system specifically aimed at CCAR measurements,
      based on low-cost commercial hardware, and that implements an adaptive research
      algorithm that selects and presents bright dots on a monitor to outline the
      borders of the blind spot, locate its center, and measure CCAR. We examined 10
      healthy subjects who underwent four CCAR measurements to evaluate the reliability
      of the system and compared our results with those of fundus photographic
      examination. Our data showed an excyclophoria, with mean ocular torsion of 6.4
      degrees  in the right and 6.7 degrees  in the left eye. These values are in
      keeping with those in the literature. Moreover, the values of the intraclass
      correlation coefficients suggest excellent reliability of the technique.

PMID- 21950999
TI  - The basis for using bone-conducted vibration or air-conducted sound to test
      otolithic function.
AB  - Extracellular single neuron recordings of primary vestibular neurons in Scarpa's
      ganglion in guinea pigs show that low-intensity 500 Hz bone-conducted vibration
      (BCV) or 500 Hz air-conducted sound (ACS) activate a high proportion of otolith
      irregular neurons from the utricular and saccular maculae but few semicircular
      canal neurons. In alert guinea pigs, and humans, 500 Hz BCV elicits otolith
      evoked eye movements. In humans, it also elicits a myogenic potential on tensed
      sternocleidomastoid muscles. Although BCV and ACS activate both utricular and
      saccular maculae, it is possible to probe the functional status of these two
      sense organs separately because of their differential neural projections.
      Saccular neurons have a strong projection to neck muscles and a weak projection
      to the oculomotor system. Utricular afferents have a strong projection to eye
      muscles. So measuring oculomotor responses to ACS and BCV predominantly probes
      utricular function, while measuring neck muscle responses to these stimuli
      predominantly probes saccular function.

PMID- 21951000
TI  - The human translational vestibulo-ocular reflex in response to complex motion.
AB  - We studied the translational vestibulo-ocular reflex (tVOR) in four healthy human
      subjects during complex, unpredictable sum-of-sines head motion (combination of
      0.73, 1.33, 1.93, and 2.93 Hz), while subjects viewed a target 15 cm away. Ideal
      eye velocity was calculated from recorded head motion; actual eye velocity was
      measured with scleral coils. The gain and phase for each frequency component was
      determined by least-squares optimization. Gain averaged approximately 40% and did
      not change with frequency; phase lag increased with frequency to a maximum of 66
      degrees . Fitting actual to ideal eye velocity predicted a tVOR latency of 48 m/s
      for vertical and 38 m/s for horizontal translation. These findings provide
      further evidence that the normal tVOR is considerably undercompensatory, even at
      low frequencies if the stimulus is not predictable. The similarity of this
      behavior to that of pursuit suggests that these two eye movements may share some
      aspects of neural processing.

PMID- 21951001
TI  - Ocular lateropulsion as a central oculomotor sign in acute vestibular syndrome is
      not posturally dependent.
AB  - Horizontal conjugate gaze deviation (h-CGD) in acute vestibular syndrome (AVS)
      may be detected clinically or radiographically. While upright clinical ocular
      lateropulsion (OL) predicts central lesions, supine radiographic h-CGD does not.
      We sought to investigate the cause for this discordance by comparing upright to
      supine OL in AVS. We prospectively recorded clinical and radiographic h-CGD in 17
      AVS patients. Horizontal eye position after brief eyelid closure was tested
      clinically following postural shifts. Radiographic h-CGD was assessed on axial
      magnetic resonance imaging (MRI) or computerized tomography (CT) images. All
      maintained central fixation with eyes open in light. OL was present in 8 (7
      strokes, one central demyelination) and radiographic h-CGD in 14 (including all 6
      with peripheral lesions). OL was unchanged after static postural testing. OL
      predicts central pathology and does not vary with postural shifts, regardless of
      lesion location. Radiographic h-CGD does not help localize, and this is not a
      positional effect.

PMID- 21951002
TI  - Vestibular perceptual thresholds to angular rotation in acute unilateral
      vestibular paresis and with galvanic stimulation.
AB  - Studies of compensation of injury to the human vestibular system have, in the
      main, focused on the vestibular-ocular reflex. Probing vestibular perception
      allows more of the sensory pathway to be assessed. We present a novel paradigm
      for simultaneously testing vestibular perceptual and nystagmic thresholds to
      angular acceleration around an earth vertical axis. The perceptual thresholds can
      be modulated asymmetrically in normal subjects by DC galvanic stimulation with
      the head flexed in the roll plane, as expected from the main torsional plane of
      action of the galvanic stimulus. The perceptual and nystagmic thresholds were
      bilaterally elevated in acute vestibular neuritis, a unilateral condition,
      possibly due to central suppression of vestibular input. The degree of asymmetry
      in thresholds was small in comparison with the large caloric asymmetry present in
      the patients, indicating a relatively preserved capacity for near-threshold
      performance of the non-damaged labyrinth both in the "on" and "off" directions.

PMID- 21951003
TI  - Visual and vestibular determinants of the translational vestibulo-ocular reflex.
AB  - Prior studies indicate that the human translational vestibulo-ocular reflex
      (tVOR) generates eye rotations approximately half the magnitude required to keep
      the line of sight pointed at a stationary object--a compensation ratio (CR) of
      ~0.5. We asked whether changes of visual or vestibular stimuli could increase the
      CR of tVOR. First, subjects viewed their environment through an optical device
      that required eye movements to increase by ~50% to maintain fixation of a
      stationary visual target. During vertical translation, eye movements did
      increase, but tVOR CR remained at ~0.5. Second, subjects viewed through LCD
      goggles providing 4 Hz strobe vision that minimized retinal image motion; this
      reduced tVOR CR. Finally, subjects were rotated in roll while they translated
      vertically; no increase in tVOR occurred. Taken with prior studies, we conclude
      that tVOR is optimally set to generate eye rotations that are about 50% of those
      required to stabilize the line of sight.

PMID- 21951004
TI  - Patterns of dissociate torsional-vertical nystagmus in internuclear
      ophthalmoplegia.
AB  - To explore the patterns and mechanisms of jerky seesaw nystagmus in internuclear
      ophthalmoplegia (INO), we analyzed the nystagmus patterns in 33 patients with
      dissociated torsional-vertical nystagmus and INO. In 11 (33%) patients, the
      nystagmus was ipsiversive torsional in both eyes with vertical components in the
      opposite directions. In contrast, 18 (55%) patients showed ipsiversive torsional
      nystagmus with a larger upbeat component in the contralesional eye. Four (12%)
      patients exhibited ipsiversive torsional nystagmus with a greater downbeat
      component in the ipsilesional eye. At least one component of contraversive ocular
      tilt reaction was associated in most patients (30/33, 91%). The patterns of jerky
      seesaw nystagmus in INO suggest a disruption of neural pathways from the
      contralateral vertical semicircular canals with or without concomitant damage to
      the fibers from the contralateral utricle in or near the medial longitudinal
      fasciculus.

PMID- 21951005
TI  - Paraneoplastic disorders of eye movements.
AB  - Paraneoplastic syndromes affecting the brainstem and cerebellum are reported to
      cause a variety of abnormalities of eye movements. Recent studies have begun to
      account for the mechanisms underlying several syndromes, characterized by
      opsoclonus, slow, or dysmetric saccades, as well as downbeat nystagmus. We
      provide evidence that upbeat nystagmus in a female patient with pancreatic cancer
      reflected a cerebellar-induced imbalance of otolithic pathways: she showed marked
      retropulsion, and her nystagmus was dependent on head position, being absent when
      supine, and suppressed with convergence. In addition to anti-Hu antibodies, we
      demonstrated antibodies to a novel neuronal cell surface antigen. Taken with
      other recent studies, our findings suggest that paraneoplastic syndromes arise
      due to antibodies against surface neuronal antigens, including receptors and
      channels. Abnormal eye movements in paraneoplastic syndromes offer insights into
      the pathogenesis of these disorders and the opportunity to test potential
      therapies, such as new drugs with effects on neuronal channels.

PMID- 21951006
TI  - Comparison of infantile nystagmus syndrome in achiasmatic zebrafish and humans.
AB  - Infantile nystagmus syndrome (INS; formerly called congenital nystagmus) is an
      ocular motor disorder characterized by several typical nystagmus waveforms. To
      date, restrictions inherent to human research and the absence of a handy animal
      model have impeded efforts to identify the underlying mechanism of INS.
      Displaying INS-like spontaneous eye oscillations, achiasmatic zebrafish
      belladonna (bel) mutants may provide new insights into the mystery of INS. In
      this study, we demonstrate that these spontaneous eye oscillations match the
      diagnostic waveforms of INS. As a result, zebrafish bel mutants can be used as an
      animal model for the study of INS. In zebrafish bel mutants, visual pathway
      abnormalities may contribute to the spontaneous nystagmus via an inverted signal
      to the pretectal area. We hypothesized that human INS may also be linked to
      visual pathway abnormalities (possibly underdiagnosed in INS patients) in a
      similar way.

PMID- 21951007
TI  - Foveal development and nystagmus.
AB  - The combination of optical coherence tomography (OCT) and genetic methods along
      with other clinical diagnostic tools permit the discrimination of infantile
      nystagmus subtypes with a precision that has not previously been possible.
      Analysis of specific diseases, such as albinism and achromatopsia as well as
      known genetic abnormalities, such as FRMD7 and PAX6 mutations, shows subtle but
      significant differences between nystagmus subtypes using eye movement recordings.
      In addition, OCT can be used to chart the progression of retinal diseases with
      age, for example, as has been shown in achromatopsia. OCT can also be used to
      predict the level of visual deficit due to retinal abnormalities, as demonstrated
      for albinism. These findings suggest that the classification of all infantile
      nystagmus into one single entity is premature.

PMID- 21951008
TI  - The mechanism of oscillopsia and its suppression.
AB  - We studied the mechanisms of oscillopsia suppression in subjects with infantile
      nystagmus syndrome, fusion maldevelopment nystagmus syndrome, and acquired
      nystagmus (AN). Hypothetical possibilities for perceptual stability were the
      following: (1) epochs of clear and stable vision during foveation periods of
      nystagmus waveforms; (2) cancellation by efference copy of motor output; (3) a
      combination of the effects of both foveation-period stability and efference-copy
      cancellation; or (4) elevated motion-detection threshold and vision suppression.
      Observations, studies, and models of oscillopsia suppression allowed comparison
      of these possibilities. Data from individual subjects supported some of the
      putative hypotheses. However, only one hypothesis remained viable that could
      explain how all subjects maintained perceptual stability despite their different
      nystagmus types, waveforms, and variability. Robust suppression of oscillopsia
      was only possible using efference-copy feedback of the motor output containing
      these specific nystagmus signals to cancel that motion from the retinal error
      signals. In cases of AN, where oscillopsia could not be suppressed, the deficit
      was postulated to interfere with or lie outside of this efference-copy feedback
      loop.

PMID- 21951009
TI  - Diffusion tensor imaging the medial longitudinal fasciculus in INO: opportunities
      and challenges.
AB  - The medial longitudinal fasciculus (MLF) is a white matter pathway in the
      brainstem that plays a key role in coordinating eye movements. Injury to the MLF
      leads to abnormalities in eye movements that can be measured with high precision
      by oculography, making it an ideal eloquent pathway to study imaging/function
      correlates. Tractography is an emerging method for identifying white matter
      pathways and offers the tantalizing promise of noninvasive, quantitative
      characterization of tissue integrity underlying functional deficits. However, the
      small caliber of the MLF and partial volume averaging with signal from nearby
      cerebrospinal fluid pose severe technical challenges to tractography-based
      delineation of the MLF. We discuss progress toward the goal of imaging the MLF
      and potential benefits of achieving this goal. Initial work suggests that ultra
      high field (7 tesla) may complement tractography for characterizing the MLF.

PMID- 21951010
TI  - Modeling the mechanisms of Uhthoff's phenomenon in MS patients with internuclear
      ophthalmoparesis.
AB  - Internuclear ophthalmoparesis (INO) is the most common saccadic eye movement
      disorder observed in patients with multiple sclerosis (MS). It is characterized
      by slowing of the adducting eye during horizontal saccades, and most commonly
      results from a demyelinating lesion in the medial longitudinal fasciculus (MLF)
      within the midline tegmentum of the pons (ventral to the fourth ventricle) or
      midbrain (ventral to the cerebral aqueduct). Recent research has demonstrated
      that adduction velocity in MS-related INO, as measured by infrared eye movement
      recording techniques, is further reduced by a systematic increase in core body
      temperature (utilizing tube-lined water infusion suits in conjunction with an
      ingestible temperature probe and transabdominal telemetry) and reversed to
      baseline with active cooling. These results suggest that INO may represent a
      model syndrome by which we can carefully study the Uhthoff's phenomenon and
      objectively test therapeutic agents for its prevention.

PMID- 21951012
TI  - Persistent ocular motor manifestations and related visual consequences in
      multiple sclerosis.
AB  - Abnormal eye movements in multiple sclerosis (MS) are often persistent and known
      to be associated with general disability. However, there is no precise knowledge
      concerning their incidence and resulting visual handicap. The aim of our study
      was to describe the persistent ocular motor manifestations in MS and relate them
      to visual functions tested with visual acuity and with a vision-related
      questionnaire. We selected 24 MS patients complaining of persistent visual
      disability associated with ocular motor manifestations without any anterior
      visual pathway deficit. Internuclear ophthalmoplegia was the most frequently
      observed symptom, followed by gaze-evoked nystagmus, saccadic hypermetria, and
      then pendular nystagmus. Pendular nystagmus, saccadic hypermetria, and the
      association of internuclear ophthalmoplegia and gaze-evoked nystagmus were
      associated with decreased visual acuity and visual functional scores. There was a
      correlation between the number of abnormal eye movements and visual functions.
      This study demonstrates that ocular motor dysfunction in MS induces specific
      visual dysfunction and handicap.

PMID- 21951011
TI  - Pharmacological tests of hypotheses for acquired pendular nystagmus.
AB  - Acquired pendular nystagmus (APN) occurs with multiple sclerosis (MS) and
      oculopalatal tremor (OPT); distinct features of the nystagmus have led to the
      development of separate models for their pathogenesis. APN in MS has been
      attributed to instability in the neural integrator, which normally ensures steady
      gaze. APN in OPT may result from electrotonic coupling between neurons in the
      hypertrophied inferior olivary nucleus, which induces maladaptive learning in
      cerebellar cortex. We tested these two hypotheses by analyzing the effects of
      gabapentin, memantine, and baclofen on both forms of nystagmus. No drug changed
      the dominant frequency of either form of APN, but the variability of frequency
      was affected with gabapentin and memantine in patients with OPT. The amplitude of
      APN in both MS and OPT was reduced with gabapentin and memantine, but not
      baclofen. Analyzing the effects of drug therapies on ocular oscillations provides
      a novel approach to test models of nystagmus.

PMID- 21951014
TI  - Human congenital diseases with mixed modes of inheritance have a shortage of
      recessive disease. A demographic scenario?
AB  - An archive of congenital human diseases is presented, aiming to contain all those
      where recessive (biallelic) can be compared with X-linked and/or dominant
      (monoallelic) inheritance. A significant deficit of recessive inheritance is
      evident, both in disease inheritance and in contribution to inheritance per known
      disease gene. The deficit contrasts with expectation derived from the cell
      biology of mutation, and from the importance of recessive mutation in evolution
      and its preponderance in N-ethyl-N-nitrosourea (ENU) mutagenesis. The deficit
      fits well with the standard model of demographic change since the neolithic era,
      and may also reflect natural selection acting on heterozygotes.

PMID- 21951015
TI  - Partially dominant mutant channel defect corresponding with intermediate LQT2
      phenotype.
AB  - BACKGROUND: The hereditary Long QT Syndrome is a common cardiac disorder where
      ventricular repolarization is delayed, abnormally prolonging the QTc interval on
      electrocardiograms. LQTS is linked to various genetic loci, including the KCNH2
      (HERG) gene that encodes the alpha-subunit of the cardiac potassium channel that
      carries I(Kr). Here, we report and characterize a novel pathologic missense
      mutation, G816V HERG, in a patient with sudden cardiac death. METHODS: Autopsy
      derived tissue sample was used for DNA extraction and sequencing from an
      unexpected sudden death victim. The G816V HERG mutation was studied using
      heterologous expression in mammalian cell culture, whole cell patch clamp,
      confocal immunofluorescence, and immunochemical analyses. RESULTS: The mutant
      G816V HERG channel has reduced protein expression and shows a trafficking
      defective phenotype that is incapable of carrying current when expressed at
      physiological temperatures. The mutant channel showed reduced cell surface
      localization compared to wild-type HERG (WT HERG) but the mutant and wild-type
      subunits are capable of interacting. Expression studies at reduced temperatures
      enabled partial rescue of the trafficking defect with appearance of potassium
      currents, albeit with reduced current density and altered voltage-dependent
      activation. Lastly, we examined a potential role for hypokalemia as a
      contributory factor to the patient's lethal arrhythmia by possible low-potassium
      induced degradation of WT HERG and haplo-insufficiency of G816V HERG. CONCLUSION:
      The G816V mutation in HERG causes a trafficking defect that acts in a partially
      dominant negative manner. This intermediate severity defect agrees with the mild
      clinical presentation in other family members harboring the same mutation.
      Possible hypokalemia in the proband induced WT HERG degradation combined with
      haplo-insufficiency may have further compromised repolarization reserve and
      contributed to the lethal arrhythmia.

PMID- 21951016
TI  - Increasing the effectiveness of messages promoting responsible undergraduate
      drinking: tailoring to personality and matching to context.
AB  - This study addressed the serious problem of college student binge drinking by
      identifying factors that improve the effectiveness of messages encouraging
      responsible drinking presented through a website simulation. We tested schema
      matching (i.e., whether the message matches the person's self-schema type or not)
      and two types of context matching (i.e., whether the message matches the topic or
      values of the message context) to determine their relative influence on the
      effectiveness of the message. We expected that messages matched to any of these
      factors would be more effective than messages not matched. Schema matching
      reduced intentions to drink while staying in/home, but topic matching reduced
      intentions to drink when going out, suggesting that different factors are
      important for messages targeting drinking behavior in different locations.
      Significant interactions between topic matching and value matching on message
      evaluation variables indicated that the message should not match the message
      context too closely. That is, there appears to be a matching threshold:
      Increasing the number of factors the message matches does not increase message
      effectiveness, possibly because it makes the message too redundant with the
      surrounding content.

PMID- 21951017
TI  - Should testosterone replacement be offered to hypogonadal men treated previously
      for prostatic carcinoma?
AB  - Androgen administration can cause prostate cancer progression, and androgen
      deprivation therapy is a commonly used therapeutic modality in the treatment of
      prostate cancer. In trying to answer the posed clinical question, this article
      reviews the risks and benefits of testosterone replacement therapy in this
      setting and the published data from clinical series. Recommendations are made
      based on the available evidence.

PMID- 21951019
TI  - Single-pixel, single-layer polymer device as a tricolor sensor with signals
      mimicking natural photoreceptors.
AB  - Color sensing procedures typically involve multiple active detectors or a
      photodetector coupled to a filter array. We demonstrate the possibility of using
      a single polymer layer based device structure for multicolor sensing. The device
      structure does not require any color filters or any subpixelation, and it
      distinguishes colors without any external bias. The color sensing relies on an
      appropriate thickness of the active polymer layer that results in a
      characteristic polarity and temporal profile of the photocurrent signal in
      response to various incident colors. The device characteristics reveal
      interesting similarities to the features observed in natural photosensitive
      systems including retinal cone cells.

PMID- 21951018
TI  - Lack of association of vitamin D receptor gene 3'-haplotypes with psoriasis in
      Croatian patients.
AB  - Cis-acting regulatory variants in biologically relevant pathways and target
      tissues are a common source of phenotypic variations and individual disease
      susceptibility. In the skin, vitamin D receptor (VDR) is a master regulator of
      epidermal barrier function, inflammation, stem cell proliferation and microbial
      defense; therefore, we tested whether VDR 3'-regulatory haplotypes, a portion of
      which affect VDR transcriptional efficiency, allelic symmetry and mRNA turnover,
      were associated with psoriasis vulgaris. For this purpose, three VDR tag
      polymorphisms that capture most of the variability of the VDR 3'-regulatory
      element (rs1544410, rs7975232 and rs731236) were genotyped by the polymerase
      chain reaction restriction fragment length polymorphism method in 180 Caucasian
      patients with chronic plaque psoriasis and 366 ethnically matched, healthy
      controls of the Croatian origin. We found no evidence of association for any of
      the selected polymorphisms. Similarly, none of the 3'-VDR restriction haplotypes
      were associated with the risk for development of psoriasis in Croatian patients.
      These results show that neither VDR 3'-restriction polymorphisms nor common 3'
      regulatory haplotypes contribute to psoriasis risk in the Croatian population.

PMID- 21951021
TI  - "The sky is falling, the sky is falling" (maybe some of it is).

PMID- 21951022
TI  - Conservative management of post-surgical urinary incontinence using applied
      kinesiology.

PMID- 21951023
TI  - Sauna as a valuable clinical tool for cardiovascular, autoimmune, toxicant-
      induced and other chronic health problems.
AB  - Sauna therapy has been used for hundreds of years in the Scandinavian region as a
      standard health activity. Studies document the effectiveness of sauna therapy for
      persons with hypertension, congestive heart failure, and for post-myocardial
      infarction care. Some individuals with chronic obstructive pulmonary disease
      (COPD), chronic fatigue, chronic pain, or addictions also find benefit. Existing
      evidence supports the use of saunas as a component of depuration (purification or
      cleansing) protocols for environmentally-induced illness. While far-infrared
      saunas have been used in many cardiovascular studies, all studies applying sauna
      for depuration have utilized saunas with radiant heating units. Overall, regular
      sauna therapy (either radiant heat or far-infrared units) appears to be safe and
      offers multiple health benefits to regular users. One potential area of concern
      is sauna use in early pregnancy because of evidence suggesting that hyperthermia
      might be teratogenic.

PMID- 21951024
TI  - The use of glucosamine, devil's claw (Harpagophytum procumbens), and acupuncture
      as complementary and alternative treatments for osteoarthritis.
AB  - Osteoarthritis is one of the most common chronic inflammatory conditions seen in
      the general population. Current pharmacological treatments focus on reduction of
      pain and increased mobility to improve overall quality of life. However, the
      relief afforded by current standard care is often insufficient and can be
      associated with significant side effects. Many patients, therefore, seek the
      option of non-standard therapies, such as nutritional and herbal supplements,
      acupuncture, and exercise regimens. Glucosamine, Harpagophytum procumbens, and
      acupuncture are among the most commonly used complementary and alternative
      medicine approaches utilized by patients suffering from osteoarthritis. Their
      clinical relevance, safety, and potential mechanisms of action are discussed in
      this review.

PMID- 21951020
TI  - Superparamagnetic plasmonic nanohybrids: shape-controlled synthesis, TEM-induced
      structure evolution, and efficient sunlight-driven inactivation of bacteria.
AB  - Magnetic materials and noble metal-based multifunctional hybrids have attracted
      much attention recently due to their unique properties and potential applications
      in a variety of fields. However, substantial challenges remain to directly obtain
      water-soluble hybrids with well-defined structures and to directly combine
      magnetic nanoparticles with nonspherical noble metals. We describe here for the
      first time a simple solvothermal method to synthesize a series of novel water
      soluble nanohybrids composed of shape-tuned Ag cores and a Fe(3)O(4) shell. We
      found that small Fe(3)O(4) grains can be well-distributed directly on the surface
      on the Ag seeds. Such hybrids have both plasmonic and significant
      superparamagnetic properties, enabling magnetic separation. The plasmon resonance
      frequency of Ag nanostructures can be fine-tuned through the interactions between
      the two components. In addition, the decorated Fe(3)O(4) nanoparticles stabilized
      the Ag nanostructures when exposed to air and natural light for a long time.
      Furthermore, an interesting structural transformation is observed in the one
      dimensional Ag-Fe(3)O(4) nanowires under high-energy electron beam. The Ag core
      can diffuse through the porous iron oxide shell, break away, and result in the
      formation of Ag nanocluster-decorated iron oxide tubes. Finally, the hybrids
      acted as a chemical template for the synthesis of Fe(3)O(4)/Au-AgCl double-layer
      nanotubes that display obvious near-infrared absorption. Importantly, the double
      layer nanotubes exhibited enhanced photocatalytic inactivation of bacteria at
      very low concentrations under natural sunlight.

PMID- 21951026
TI  - A case report of a 53-year-old female with rheumatoid arthritis and osteoporosis:
      focus on lab testing and CAM therapies.
AB  - A 53-year-old female presented with rheumatoid arthritis and osteoporosis.
      Additional conditions and symptoms included Raynaud syndrome, fatigue, irritable
      bowel syndrome associated constipation (IBS-C), gastroesophageal reflux (GERD),
      menopausal symptoms, chronic urinary tract and upper respiratory infections, and
      weight gain. She was taking Arthrotec (a combination of diclofenac and
      misoprostol - for pain and inflammation), Fosamax Plus D (alendronate with
      vitamin D3 - recently prescribed because of low bone density), and Catapres
      (clonidine - for menopausal symptoms). Against the advice of her rheumatologist,
      she had recently discontinued taking Plaquenil (hydroxychloroquine),
      methotrexate, and prednisone due to significant side effects. Lab tests to
      identify underlying imbalances and to direct treatment were ordered. Treatment
      included dietary, nutritional, hormonal, and mind/body support. After one year of
      therapy, the patient experienced improvement with all of her presenting
      conditions and symptoms, which enabled her to discontinue several medications.
      She became versed in identifying and avoiding the environmental triggers of her
      disease, including foods (dairy, wheat, eggs, and soy), molds, and emotional
      stress. Antinuclear antibodies were normalized. She experienced a 7.5-percent
      improvement in left trochanteric bone density - comparable to bisphosphonate
      therapy. Mild improvements were also noted in the spine and bilateral femoral
      neck.

PMID- 21951025
TI  - Reassessing bioavailability of silymarin.
AB  - Silymarin, a flavonolignan derived from Silybum marianum, possesses diverse
      pharmacological activities, including hepatoprotective, antioxidant, anti
      inflammatory, anticancer, and cardioprotective. Although clinical trials have
      shown silymarin is safe at high doses (>1500 mg/day) in humans, the
      pharmacokinetic studies over the past three decades related to absorption,
      distribution, metabolism, and excretion of silymarin have revealed poor
      absorption, rapid metabolism, and ultimately poor oral bioavailability. For
      optimum silymarin bioavailability, issues of solubility, permeability,
      metabolism, and excretion must be addressed. An array of methods have been
      described in recent years that can improve its bioavailability, including
      complexation with beta-cyclodextrins, solid dispersion method, formation of
      microparticles and nanoparticles, self-microemulsifying drug delivery systems,
      micelles, liposomes, and phytosomes. This article critically reviews the recent
      published literature on various techniques for increasing the bioavailability of
      silymarin.

PMID- 21951027
TI  - Pantothenic acid. Monograph.

PMID- 21951028
TI  - Argan oil. Monograph.

PMID- 21951029
TI  - Extended utility of molten-salt chemistry: unprecedented synthesis of a water
      soluble salt-inclusion solid comprised of high-nuclearity vanadium oxide
      clusters.
AB  - Polyoxometallates (POMs) are desirable in materials applications ranging from
      uses as catalysts in selective oxidation reactions to molecular-like building
      blocks for the preparation of new extended solids. With the use of an
      unprecedented approach involving high temperature, molten salt methods, a
      fascinating series of salt-inclusion solids (SISs) that contain high nuclearity
      POMs has been isolated for the first time. Cs(11)Na(3)(V(15)O(36))Cl(6) (1) was
      synthesized using the eutectic NaCl/CsCl flux (mp 493  degrees C) which serves as
      a reactive solvent in crystal growth and allows for the SIS formation. Its
      framework can be viewed as an "ionic" lattice composed of alternately packed
      counterions of Cl-centered [V(15)O(36)Cl](9-) clusters (V15; S = 11/2) and
      multinuclear [Cs(9)Na(3)Cl(5)](7+) cations. In light of the structural analysis,
      1 was proven to be soluble in water giving rise to a dark green solution that is
      similar in color to single crystals of the title compound. Infrared spectroscopy
      of the solid formed from fast evaporation of the solution supports the presence
      of dissolved V15 clusters. Also noteworthy is the magnetization of 1 at 2 K,
      which reveals an s-shaped plot resembling that of superparamagnetic materials.

PMID- 21951030
TI  - Evaluating the cost-effectiveness of reduced mild hypoglycaemia in subjects with
      Type 1 diabetes treated with insulin detemir or NPH insulin in Denmark, Sweden,
      Finland and the Netherlands.
AB  - AIMS: To estimate short-term cost-effectiveness of insulin detemir vs. NPH
      insulin based on the incidence of mild hypoglycaemia in subjects with Type 1
      diabetes in Denmark, Sweden, Finland and the Netherlands. METHODS: A model was
      developed to evaluate cost-effectiveness based on mild (self-treated)
      hypoglycaemia and pharmacy costs over 1 year. Published rates of mild
      hypoglycaemia were used for NPH insulin and insulin detemir. Effectiveness was
      calculated in terms of quality-adjusted life expectancy. Pharmacy costs were
      accounted using published prices and defined daily doses for both insulins. Costs
      were expressed in 2010 euros (?). RESULTS: Treatment with insulin detemir was
      associated with fewer mild hypoglycaemic events than NPH insulin (mean rates of
      26.3 vs. 35.5 events per person-year), leading to an improvement in mean quality
      adjusted life expectancy of approximately 0.019 (0.030) quality-adjusted life
      years (standard deviation). Annual costs were ? 573.55 (110.42) vs. ? 332.76
      (62.18) in Denmark for insulin detemir and NPH insulin, respectively. These
      values were ? 545.79 (106.54) vs. ? 306.12 (57.78) in Sweden, ? 720.10 (140.74)
      vs. ? 408.73 (78.61) in Finland and ? 584.01 (109.47) vs. ? 359.60 (64.84) in the
      Netherlands. Incremental cost-effectiveness ratios were approximately ? 12,644
      (Denmark), ? 12,612 (Sweden), ? 16,568 (Finland) and ? 12,216 (the Netherlands)
      per quality-adjusted life year gained for insulin detemir vs. NPH insulin.
      CONCLUSIONS: Insulin detemir is likely to be cost-effective vs. NPH insulin in
      subjects with Type 1 diabetes in Denmark, Sweden, Finland and the Netherlands.
      Increased pharmacy costs with insulin detemir should not be a barrier to therapy
      based on these findings.

PMID- 21951031
TI  - 'Living stones' reveal alternative petal identity programs within the core
      eudicots.
AB  - Petals, defined as the showy laminar floral organs in the second floral whorl,
      have been shown to be under similar genetic control in distantly related core
      eudicot model organisms. On the basis of these findings, it is commonly assumed
      that the petal identity program regulated by B-class MADS-box gene homologs is
      invariant across the core eudicot clade. However, the core eudicots, which
      comprise >70% of angiosperm species, exhibit numerous instances of petal and
      sepal loss, transference of petal function between floral whorls, and recurrent
      petal evolution. In the face of these complex patterns of perianth evolution, the
      concept of a core eudicot petal identity program has not been tested. We
      therefore examined the petal identity program in the Caryophyllales, a core
      eudicot clade in which perianth differentiation into sepals and petals has
      evolved multiple times. Specifically, we analyzed the expression patterns of B-
      and C-class MADS-box homologs for evidence of a conserved petal identity program
      between sepal-derived and stamen-derived petaloid organs in the 'living stone'
      family Aizoaceae. We found that neither sepal-derived nor stamen-derived petaloid
      organs exhibit gene expression patterns consistent with the core eudicot petal
      identity program. B-class gene homologs are not expressed during the development
      of sepal-derived petals and are not implicated in petal identity in stamen
      derived petals, as their transient expression coincides with early expression of
      the C-class homolog. We therefore provide evidence for petal development that is
      independent of B-class genes and suggest that different genetic control of petal
      identity has evolved within this lineage of core eudicots. These findings call
      for a more comprehensive understanding of perianth variation and its genetic
      causes within the core eudicots--an endeavor that will have broader implications
      for the interpretation of perianth evolution across angiosperms.

PMID- 21951032
TI  - The effect of topical vancomycin applied to sternotomy incisions on postoperative
      serum vancomycin levels.
AB  - BACKGROUND AND AIM: Topical vancomycin has been shown to reduce the incidence of
      sternal wound infections but concerns have been raised that persistent serum
      levels of vancomycin may contribute to the emergence of drug-resistant
      infections. This study was undertaken to determine: (1) whether serum levels of
      vancomycin remain elevated when applied topically to the sternum and (2) whether
      the use of topical vancomycin can potentiate postoperative drug-resistant
      infections. METHODS: Serum vancomycin levels were measured on the evening of
      surgery and the sixth postoperative day in 36 patients in which topical
      vancomycin was applied to the cut edges of the sternum during their cardiac
      surgical procedures. Data are presented as a mean +/- standard deviation and
      statistical significance was tested using paired t-test analyses. RESULTS: There
      was a significant decrease in serum vancomycin levels from the night of surgery
      to the sixth postoperative day (11.5 +/- 1.9 MUg/mL to 2.12 +/- 0.79 MUg/mL; p
      <0.0001). The incidence of sternal infections was 0% and no patient developed any
      infection or had renal toxicity during the 12-month follow-up. CONCLUSIONS: The
      use of topical vancomycin applied to the sternotomy incision does not result in
      persistently elevated levels of serum vancomycin following cardiac surgical
      procedures. Furthermore, topical vancomycin does not potentiate the emergence of
      drug-resistant infections or contribute to postoperative renal toxicity. 

PMID- 21951033
TI  - Long-term outcomes in octogenarians following aortic valve replacement.
AB  - BACKGROUND: The aging of the population has resulted in an increasing number of
      elderly patients undergoing cardiac operations. We reviewed our experience in
      patients over the age of 80 undergoing primary aortic valve replacement (AVR)
      with or without CABG. METHODS: Between 2000 and 2008, 345 patients (226 male)
      >=80 years underwent primary AVR in our unit. The notes of these patients were
      retrospectively reviewed and follow-up information was obtained from their
      general practitioners. They had a mean age of 82.9 +/- 2.3 years and a median
      logistic EuroSCORE of 13.4 (IQR 9.4, 19.1). Isolated AVR was performed in 161
      patients (45.5%), and 184 (51.6%) patients underwent combined AVR and CABG. A
      quality of life questionnaire was sent to all survivors. RESULTS: Hospital
      mortality occurred in 17 patients (4.9%), which was significantly lower than the
      mortality predicted by logistic EuroSCORE (16.2%, p < 0.01). Hospital mortality
      was comparable between patients undergoing isolated AVR and those undergoing
      additional CABG (4.3% vs. 5.4%, respectively). Actuarial survival at one and five
      years was 90.1 +/- 1.6% and 77.2 +/- 2.9%, respectively. There was a 62% response
      on the questionnaire showing 70% of the patients were NYHA I and 83.7% were
      satisfied with the operation outcome. CONCLUSIONS: AVR can be undertaken with
      excellent results in octogenarians and the current risk is significantly lower
      than what is predicted with conventional risk-scoring systems. Patients with
      advanced age should not necessarily be excluded from being candidates for AVR. 

PMID- 21951034
TI  - Resolution of recurrent chest pain with resection of papillary fibroelastoma.
AB  - Papillary fibroelastoma (PFE) is a benign primary tumor of the heart usually
      originating from the heart valves. Nonvalvular fibroelastomas are rare, and
      reported cases have presented either incidentally or with cerebral embolic
      phenomena; none have reported recurrent anginal symptoms. We are reporting a case
      of a 53-year-old female with history of significant radiation exposure to the
      chest in the past, who presented with recurrent chest pain and was found to have
      left atrial nonvalvular PFE managed with surgical excision. 

PMID- 21951035
TI  - Repair of iatrogenic aortic regurgitation following cardiac catheterization.
AB  - Acute aortic regurgitation (AR) related to left cardiac catheterization is an
      exceedingly rare complication. Valve repair is the best therapeutic option in
      case of isolated AR. We report the successful repair of an aortic valve tear
      following cardiac catheterization. 

PMID- 21951036
TI  - Unligated left internal mammary artery side branch resulting in coronary artery
      steal syndrome.
AB  - Whether internal mammary artery side branches have the potential for
      hemodynamically significant flow steal in cases of postcoronary surgery ischemia
      remains a controversial issue. We present a case in which coil embolization of
      two unligated side branches resulted in symptomatic improvement and resolution of
      ischemia as evidenced by myoview imaging. 

PMID- 21951037
TI  - Surgical repair of late aortic dissection after cardiac surgery.
AB  - Late aortic dissection is a rare but serious complication associated with cardiac
      surgery. We report two cases of late aortic dissection that occurred after
      cardiac surgery. The management and review of the preoperative factors, which may
      predispose to this complication, are the subject of this case report. 

PMID- 21951038
TI  - Aortico-right ventricular tunnel with anomalous right coronary artery.
AB  - Two patients with aortic right ventricular tunnel and anomalous origin of the
      right coronary artery from the tunnel are reported. The literature on this
      condition is reviewed. 

PMID- 21951039
TI  - Supracardiac total anomalous pulmonary venous connection with severe rheumatic
      mitral valve disease.
AB  - A rare association of supracardiac total anomalous pulmonary venous connection
      (TAPVC) along with severe rheumatic mitral regurgitation is presented. The
      patient, a 28-year-old female, underwent successful repair of the TAPVC along
      with pericardial patch closure of the atrial septal defect and replacement of the
      mitral valve with a mechanical prosthesis. 

PMID- 21951040
TI  - Timely use of a CentriMag heart assist device improves survival in postcardiotomy
      cardiogenic shock.
AB  - BACKGROUND: Postcardiotomy cardiogenic shock (PCS) is often fatal despite
      inotropic and circulatory support. We compared our experience with the CentriMag
      left ventricular assist device (LVAD) for patients with PCS at two time periods:
      in the operating room (OR) after unsuccessful weaning from cardiopulmonary bypass
      (CPB) and after transfer to the intensive care unit (ICU). METHODS: We reviewed
      22 patients' records (13 men, nine women; age, 65 +/- 12 years) who underwent
      open heart surgery (January 2004 to September 2009) and required LVAD support for
      PCS despite maximal inotropic and intra-aortic balloon pump (IABP) support. In
      ten patients who could not be weaned from CPB despite high-dose inotropic therapy
      (>= 3 agents) and IABP support, the CentriMag was implanted in the OR (immediate
      group). The other 12 patients were weaned from CPB with high-dose inotropic
      therapy and IABP but became increasingly unstable or had a cardiac arrest in the
      ICU, and the CentriMag was implanted for circulatory support (delayed group).
      RESULTS: Preoperatively, the average ejection fraction was 40% +/- 12%, the
      creatinine level was 1.6 +/- 0.6 mg/dL, and the European Systematic Coronary Risk
      Evaluation was 13.1 +/- 4.6. The duration of CentriMag support was 5 +/- 3 days.
      The immediate group had significantly better survival (7/10 vs. 2/12, p = 0.027),
      higher cardiac index (2.4 +/- 0.3 L/min/m(2) vs. 1.7 +/- 0.3 L/min/m(2), p =
      0.001), and lower pulmonary capillary wedge pressure (20 +/- 6 mmHg vs. 29 +/- 8
      mmHg, p = 0.024) than the ICU group. No perioperative complications related to
      device implantation occurred. CONCLUSION: In patients with PCS, timely placement
      of a CentriMag LVAD may increase the chance of eventual recovery. 

PMID- 21951050
TI  - Track structure calculations on intracellular targets responsible for signal
      release in bystander experiments with transfer of irradiated cell-conditioned
      medium.
AB  - PURPOSE: To investigate alternative scenarios for the dose-dependent emission of
      bystander signals by irradiated cells in medium transfer experiments. METHODS:
      Energy deposition patterns to hypothetical intracellular targets whose hit by
      radiation initiates the emission of bystander signals have been simulated by
      Monte Carlo code PARTRAC, evaluating the effects of target size, multiplicity and
      threshold energy for activation. Scenarios in which individual irradiated cells
      release signals independently as well as those with signal amplification by
      neighbour cells have been analyzed. The non-linear response of unirradiated cells
      to signals in the transferred medium has been considered. RESULTS: The
      experimentally observed dose dependence of bystander effects is consistent with
      cell-autonomous signal release with a wide distribution of characteristic doses,
      covering the range of 3 mGy to 3 Gy. Alternatively, the data can be explained by
      assuming that only cells receiving a high specific energy (3 Gy to 0.5 MUm
      targets) release primary signals, which are then amplified by secondary
      signalling by neighbour cells within about a millimetre distance. CONCLUSION:
      Alternative signal emission scenarios are consistent with the observed dose
      dependence of bystander effects in medium transfer experiments. Thus, further
      experimental research is needed to identify the actual mechanism of bystander
      signal emission.

PMID- 21951051
TI  - A calorimetric and spectroscopic comparison of the effects of lathosterol and
      cholesterol on the thermotropic phase behavior and organization of
      dipalmitoylphosphatidylcholine bilayer membranes.
AB  - We performed differential scanning calorimetry (DSC) and Fourier transform
      infrared (FTIR) spectroscopic measurements to study the effects of lathosterol
      (Lath) on the thermotropic phase behavior and organization of
      dipalmitoylphosphatidylcholine (DPPC) bilayer membranes and compared our results
      with those previously reported for cholesterol (Chol)/DPPC binary mixtures. Lath
      is the penultimate intermediate in the biosynthesis of Chol in the Kandutsch
      Russell pathway and differs from Chol only in the double bond position in ring B,
      which is between C7 and C8 in Lath and between C5 and C6 in Chol. Our DSC studies
      indicate that the incorporation of Lath is more effective than Chol in reducing
      the temperature and enthalpy of the DPPC pretransition. At lower sterol
      concentrations (<=10 mol %), incorporation of both Lath and Chol decreases the
      temperature, enthalpy, and cooperativity of the sharp component of the main phase
      transition of DPPC to a similar extent, but at higher sterol concentrations, Lath
      is more effective at decreasing the phase transition temperature, enthalpy, and
      cooperativity than Chol. These results indicate that at higher concentrations,
      Lath is more disruptive of DPPC gel-state bilayer packing than Chol is. Moreover,
      incorporation of Lath decreases the temperature of the broad component of the
      main phase transition of DPPC, whereas Chol increases it; this difference in the
      direction and magnitude of the temperature shift is accentuated at higher sterol
      concentrations. Although at sterol concentrations of <=20 mol % Lath and Chol are
      almost equally effective at reducing the enthalpy and cooperativity of the broad
      component of the main phase transition, at higher sterol levels Lath is less
      effective than Chol in these regards and does not completely abolish the
      cooperative hydrocarbon chain melting phase transition at 50 mol %, as does Chol.
      These latter results indicate that Lath both is more disruptive with respect to
      the low-temperature state of the sterol-enriched domains of DPPC bilayers and has
      a lower lateral miscibility in DPPC bilayers than Chol. Our FTIR spectroscopic
      studies suggest that Lath incorporation produces a less tightly packed bilayer
      than does Chol at both low (gel state) and high (liquid-crystalline state)
      temperatures, which is characterized by increased H-bonding between water and the
      carbonyl groups of the fatty acyl chains in the DPPC bilayer. Overall, our
      studies indicate that Lath and Chol incorporation can have rather different
      effects on the thermotropic phase behavior and organization of DPPC bilayers and
      thus that the position of the double bond in ring B of a sterol molecule can have
      an appreciable effect on the physical properties of sterol molecules.

PMID- 21951052
TI  - Normative adjustments to the D-KEFS trail making test: corrections for education
      and vocabulary level.
AB  - The Delis-Kaplan Executive Function System (D-KEFS) Trail Making Test (TMT), a
      modification of the original TMT, was created to isolate set-shifting (Letter
      Number Switching) from other component skills. This was accomplished by including
      four baseline conditions (Visual Scanning, Number Sequencing, Letter Sequencing,
      and Motor Speed) and by placing equal numbers of stimuli in the three sequencing
      conditions. Given that some studies with the original TMT demonstrated a
      significant effect of education and intellectual functioning on performance, we
      utilized the D-KEFS national standardization sample to examine the effects of
      education and vocabulary level-i.e., Vocabulary subtest from the Wechsler
      Abbreviated Scale of Intelligence (WASI)-on the D-KEFS TMT. The results indicate
      a significant effect of these variables on each D-KEFS TMT condition. Normative
      tables for education- and vocabulary-adjusted scaled scores based on the database
      from the D-KEFS national normative study were generated.

PMID- 21951053
TI  - IsoLasso: a LASSO regression approach to RNA-Seq based transcriptome assembly.
AB  - The new second generation sequencing technology revolutionizes many biology
      related research fields and poses various computational biology challenges. One
      of them is transcriptome assembly based on RNA-Seq data, which aims at
      reconstructing all full-length mRNA transcripts simultaneously from millions of
      short reads. In this article, we consider three objectives in transcriptome
      assembly: the maximization of prediction accuracy, minimization of
      interpretation, and maximization of completeness. The first objective, the
      maximization of prediction accuracy, requires that the estimated expression
      levels based on assembled transcripts should be as close as possible to the
      observed ones for every expressed region of the genome. The minimization of
      interpretation follows the parsimony principle to seek as few transcripts in the
      prediction as possible. The third objective, the maximization of completeness,
      requires that the maximum number of mapped reads (or ?expressed segments? in gene
      models) be explained by (i.e., contained in) the predicted transcripts in the
      solution. Based on the above three objectives, we present IsoLasso, a new RNA-Seq
      based transcriptome assembly tool. IsoLasso is based on the well-known LASSO
      algorithm, a multivariate regression method designated to seek a balance between
      the maximization of prediction accuracy and the minimization of interpretation.
      By including some additional constraints in the quadratic program involved in
      LASSO, IsoLasso is able to make the set of assembled transcripts as complete as
      possible. Experiments on simulated and real RNA-Seq datasets show that IsoLasso
      achieves, simultaneously, higher sensitivity and precision than the state-of-art
      transcript assembly tools.

PMID- 21951054
TI  - An optimization-based sampling scheme for phylogenetic trees.
AB  - Much modern work in phylogenetics depends on statistical sampling approaches to
      phylogeny construction to estimate probability distributions of possible trees
      for any given input data set. Our theoretical understanding of sampling
      approaches to phylogenetics remains far less developed than that for optimization
      approaches, however, particularly with regard to the number of sampling steps
      needed to produce accurate samples of tree partition functions. Despite the many
      advantages in principle of being able to sample trees from sophisticated
      probabilistic models, we have little theoretical basis for concluding that the
      prevailing sampling approaches do in fact yield accurate samples from those
      models within realistic numbers of steps. We propose a novel approach to
      phylogenetic sampling intended to be both efficient in practice and more amenable
      to theoretical analysis than the prevailing methods. The method depends on
      replacing the standard tree rearrangement moves with an alternative Markov model
      in which one solves a theoretically hard but practically tractable optimization
      problem on each step of sampling. The resulting method can be applied to a broad
      range of standard probability models, yielding practical algorithms for efficient
      sampling and rigorous proofs of accurate sampling for heated versions of some
      important special cases. We demonstrate the efficiency and versatility of the
      method by an analysis of uncertainty in tree inference over varying input sizes.
      In addition to providing a new practical method for phylogenetic sampling, the
      technique is likely to prove applicable to many similar problems involving
      sampling over combinatorial objects weighted by a likelihood model.

PMID- 21951055
TI  - A probabilistic model for sequence alignment with context-sensitive indels.
AB  - Probabilistic approaches for sequence alignment are usually based on pair Hidden
      Markov Models (HMMs) or Stochastic Context Free Grammars (SCFGs). Recent studies
      have shown a significant correlation between the content of short indels and
      their flanking regions, which by definition cannot be modelled by the above two
      approaches. In this work, we present a context-sensitive indel model based on a
      pair Tree-Adjoining Grammar (TAG), along with accompanying algorithms for
      efficient alignment and parameter estimation. The increased precision and
      statistical power of this model is shown on simulated and real genomic data. As
      the cost of sequencing plummets, the usefulness of comparative analysis is
      becoming limited by alignment accuracy rather than data availability. Our results
      will therefore have an impact on any type of downstream comparative genomics
      analyses that rely on alignments. Fine-grained studies of small functional
      regions or disease markers, for example, could be significantly improved by our
      method. The implementation is available at
      www.mcb.mcgill.ca/~blanchem/software.html.

PMID- 21951057
TI  - Peculiarities of the environmental influence on the optical properties of push
      pull nonlinear optical molecules: a theoretical study.
AB  - Gas-phase geometry optimization of NLO-active molecules is one of the standard
      approaches in the first principle computational methodology, whereas the
      important role of the environment is usually not considered during the evaluation
      of structural parameters. With a wide variety of environmentally influenced
      models in most cases only the high quality single point calculations are
      prepared. Among different approaches, the most used polarizable continuum model
      (PCM) seems to be promising. In this study, we have compared the electronic
      properties of gas-phase optimized geometries of imidazole-derived push-pull
      compounds with those optimized using PCM solvation approach including CH(2)Cl(2)
      and PMMA as media. We have focused particularly on the linear optical properties
      of investigated molecules, namely on the UV-vis absorption spectra. The analysis
      of presented results shows the applicability of the different quantum chemical
      (QC) methods for the UV-vis spectra calculations of linear NLO molecules. Herein
      we also present the need of molecule geometry optimization affected by the
      environment. Following the performed calculations, the electronic properties of
      gas-phase optimized molecules give conformable results with respect to those
      obtained by more time-consuming continuum optimizations. All computational data
      are supported by experimental investigations.

PMID- 21951056
TI  - A novel compound PTIQ protects the nigral dopaminergic neurones in an animal
      model of Parkinson's disease induced by MPTP.
AB  - BACKGROUND AND PURPOSE: In Parkinson's disease, the dopaminergic neurones in the
      substantia nigra undergo degeneration. While the exact mechanism for the
      degeneration is not completely understood, neuronal apoptosis and
      neuroinflammation are thought to be key contributors. We have recently
      established that MMP-3 plays crucial roles in dopaminergic cell death and
      microglial activation. EXPERIMENTAL APPROACH: We tested the effects of 7-hydroxy
      6-methoxy-2-propionyl-1,2,3,4-tetrahydroisoquinoline (PTIQ) on expression of MMP
      3 and inflammatory molecules and dopaminergic cell death in vitro and in an
      animal model of Parkinson's disease, and Parkinson's disease-related motor
      deficits. The pharmacokinetic profile of PTIQ was also evaluated. KEY RESULTS:
      PTIQ effectively suppressed the production of MMP-3 induced in response to
      cellular stress in the dopaminergic CATH.a cell line and prevented the resulting
      cell death. In BV-2 microglial cells activated with lipopolysaccharide, PTIQ down
      regulated expression of MMP-3 along with IL-1beta, TNF-alpha and cyclooxygenase-2
      and blocked nuclear translocation of NF-kappaB. In the mouse model of Parkinson's
      disease ,induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), PTIQ
      attenuated the associated motor deficits, prevented neurodegeneration and
      suppressed microglial activation in the substantia nigra. Pharmacokinetic
      analysis showed it was relatively stable against liver microsomal enzymes, did
      not inhibit the cytochrome p450 isozymes or the hERG ion channel, exhibited no
      cytotoxicity on liver cells or lethality when administered at 1000 mg kg(-1) and
      entered the brain rather rapidly yielding a 28% brain:plasma ratio after i.p.
      injection. CONCLUSIONS AND IMPLICATIONS: These results suggest PTIQ has potential
      as a candidate drug for disease-modifying therapy for Parkinson's disease.

PMID- 21951058
TI  - A quantum probability account of order effects in inference.
AB  - Order of information plays a crucial role in the process of updating beliefs
      across time. In fact, the presence of order effects makes a classical or Bayesian
      approach to inference difficult. As a result, the existing models of inference,
      such as the belief-adjustment model, merely provide an ad hoc explanation for
      these effects. We postulate a quantum inference model for order effects based on
      the axiomatic principles of quantum probability theory. The quantum inference
      model explains order effects by transforming a state vector with different
      sequences of operators for different orderings of information. We demonstrate
      this process by fitting the quantum model to data collected in a medical
      diagnostic task and a jury decision-making task. To further test the quantum
      inference model, a new jury decision-making experiment is developed. Using the
      results of this experiment, we compare the quantum inference model with two
      versions of the belief-adjustment model, the adding model and the averaging
      model. We show that both the quantum model and the adding model provide good fits
      to the data. To distinguish the quantum model from the adding model, we develop a
      new experiment involving extreme evidence. The results from this new experiment
      suggest that the adding model faces limitations when accounting for tasks
      involving extreme evidence, whereas the quantum inference model does not.
      Ultimately, we argue that the quantum model provides a more coherent account for
      order effects that was not possible before.

PMID- 21951059
TI  - Numerical solution for water table rise estimation behind deep underground dam.
AB  - A comprehensive numerical approach has been developed to solve the transient
      groundwater level changes due to the construction of underground dams. This
      method assumes no flow takes place through the dam and does not require knowledge
      of either the dam hydraulic properties or information about downstream water
      table changing level or aquifer geometry beyond the dam site. It couples the
      solution of the general groundwater flow equation with a modified equation
      derived at the lower boundary nodes of the simulated domain. The robustness of
      this method has been tested against simulations of the full groundwater equation
      for different time periods of up to 50 years with different aquifer
      characteristics. Comparison shows good agreement between the developed model
      outputs and the full groundwater flow equation simulated results, under the
      different simulated scenarios.

PMID- 21951060
TI  - Tuning surface wettability of In(x)Ga(1-x)N nanotip arrays by phosphonic acid
      modification and photoillumination.
AB  - We report a facile route to reversibly tune surface wettability of In(x)Ga((1
      x))N (InGaN) nanotip arrays by octylphosphonic acid (OPA) modification and
      ultraviolet-visible (UV-vis) light illuminations. Well-aligned InGaN nanotip
      arrays were grown by chemical vapor deposition (CVD). OPA was covalently attached
      to the InGaN nanotip surface, which was initially oxidized in Piranha solution.
      Because of the high surface energy of polar groups, OPA-coated InGaN nanotip
      arrays demonstrated superhydrophobic properties (contact angle of 154 degrees ).
      Transitions between superhydrophobicity and hydrophilicity were obtained through
      OPA adsorption and UV-vis light illumination. The InGaN nanotip surface chemistry
      was further characterized by X-ray photoelectron spectroscopy (XPS), which
      suggested a scission mechanism at P-C and MO-P (M = In and Ga) bonds of bound OPA
      molecules. Meanwhile, no significant surface degradation was observed after the
      OPA modification and phototreatments.

PMID- 21951061
TI  - Combined effect of DHA and alpha-tocopherol supplementation during bull semen
      cryopreservation on sperm characteristics and fatty acid composition.
AB  - The aim of this study was to investigate the effect of adding n-3 fatty acids
      (FA) and alpha-tocopherol (VE) to semen extender on freezing ability and FA
      composition of bull sperm. Semen was collected from 10 Iranian Holstein bulls and
      was pooled. In the first experiment, semen was divided into 12 groups including 4
      levels of n-3 FA (0, 0.1, 1, 10 ng ml(-1) ) and 3 levels of VE (0, 0.1, 0.2
      mmol). The treatment of 0.2 mmol VE and 10 ng ml(-1) n-3 FA had the best post
      thawed sperm characteristics (P < 0.01). In the second experiment, lipid
      composition of the latest treatment and control (without FA and VE) was
      determined. Adding n-3 FA increased docosahexaenoic acid (DHA) percentage before
      freezing and after thawing. The ratio of n-3 to n-6 before freezing was higher (P
      < 0.05) in treated group than in control, and this ratio in the fresh sperm was
      greater than in the post-thawed sperm (P = 0.1). Results suggested that adding
      DHA accompanied with an antioxidant to an extender could improve cryosurvival of
      bull sperm via altering membrane lipid composition.

PMID- 21951062
TI  - Effects of topical application of EGCG on testosterone-induced hair loss in a
      mouse model.
AB  - We investigated the effect of topical epigallocatechin-3-gallate (EGCG) on
      testosterone (T)-induced hair loss in mice. Marked hair loss was observed at the
      T-injected site, and topical EGCG significantly reduced the hair loss (P < 0.05).
      TUNEL staining showed apoptosis of follicular epithelial cells in the T-injected
      groups where topical EGCG was found to significantly diminish T-induced apoptosis
      (P < 0.05). Topical EGCG down-regulated the T-induced expression of androgen
      receptor but did not down-regulate 17beta-hydroxysteroid dehydrogenase (HSD) and
      three beta-HSD expression. Analysis using liquid chromatography tandem mass
      spectrometry (LC-MS/MS) on serum and tissue samples revealed no significant
      difference in T and dihydrotestosterone concentrations between the T-injected and
      T + EGCG groups. Thus, we found that T injection in a mouse model induces hair
      loss by apoptosis of the hair follicles rather than through the androgen
      metabolic pathway and also saw that T-induced apoptosis of hair follicles was
      reduced by topical EGCG.

PMID- 21951064
TI  - Neonatal extracorporeal life support: will the newest technology reduce
      morbidity?
AB  - The objectives of this review are to describe the Extracorporeal Life Support
      (ECLS) research at the Penn State Pediatric Cardiovascular Research evaluating
      new pediatric ECLS components and to discuss a proposed continuous quality
      improvement model after implementation of new technology. Review of current
      literature pertaining to studies at the Penn State Hershey Children's Hospital
      (PSHCH) is presented along with a retrospective chart review of ECLS pediatric
      patients from January 2000 to June 2010. We describe improvements in the newest
      hollow-fiber oxygenator demonstrating a lower pressure drop (compared with
      silicone), and in the newest RotaFlow centrifugal pump which allows higher
      hemodynamic energy delivered to the patient at higher flow rates with less
      retrograde flow. The miniaturized pediatric circuit implemented is portable and
      primes quickly for rapid deployment. Our model of continuous quality improvement
      includes in-depth evaluation of all circuit component performance through on-site
      in vivo and in vitro testing at the PSHCH. We utilize the same model to provide
      comprehensive education and hands-on training of the staff. This cycle can be
      repeated for evaluation and implementation of any new circuit component. Our
      comprehensive approach to ECLS may provide the ideal means from which to safely
      introduce new technology.

PMID- 21951063
TI  - Cannabinoid CB(2)  receptors modulate ERK-1/2 kinase signalling and NO release in
      microglial cells stimulated with bacterial lipopolysaccharide.
AB  - BACKGROUND AND PURPOSE: Cannabinoid (CB) receptor agonists have potential utility
      as anti-inflammatory drugs in chronic immune inflammatory diseases. In the
      present study, we characterized the signal transduction pathways affected by
      CB(2) receptors in quiescent and lipopolysaccharide (LPS)-stimulated murine
      microglia. EXPERIMENTAL APPROACH: We examined the effects of the synthetic CB(2)
      receptor ligand, JWH-015, on phosphorylation of MAPKs and NO production. KEY
      RESULTS: Stimulation of CB(2) receptors by JWH-015 activated JNK-1/2 and ERK-1/2
      in quiescent murine microglial cells. Furthermore, CB(2) receptor activation
      increased p-ERK-1/2 at 15 min in LPS-stimulated microglia. Surprisingly, this was
      reduced after 30 min in the presence of both LPS and JWH-015. The NOS inhibitor L
      NAME blocked the ability of JWH-015 to down-regulate the LPS-induced p-ERK
      increase, indicating that activation of CB(2) receptors reduced effects of LPS on
      ERK-1/2 phosphorylation through NO. JWH-015 increased LPS-induced NO release at
      30 min, while at 4 h CB(2) receptor stimulation had an inhibitory effect. All the
      effects of JWH-015 were significantly blocked by the CB(2) receptor antagonist AM
      630 and, as the inhibition of CB(2) receptor expression by siRNA abolished the
      effects of JWH-015, were shown to be mediated specifically by activation of CB(2)
      receptors. CONCLUSIONS AND IMPLICATIONS: Our results demonstrate that CB(2)
      receptor stimulation activated the MAPK pathway, but the presence of a second
      stimulus blocked MAPK signal transduction, inhibiting pro-inflammatory LPS
      induced production of NO. Therefore, CB(2) receptor agonists may promote anti
      inflammatory therapeutic responses in activated microglia.

PMID- 21951065
TI  - Eruptive disseminated porokeratosis following bone marrow transplantation for
      acute lymphoblastic leukemia in a child.

PMID- 21951067
TI  - Optimized preparation method of platelet-concentrated plasma and noncoagulating
      platelet-derived factor concentrates: maximization of platelet concentration and
      removal of fibrinogen.
AB  - Platelet-rich plasma (PRP) has been clinically used as an easily prepared growth
      factor cocktail that can promote wound healing, angiogenesis, and tissue
      remodeling. However, the therapeutic effects of PRP are still controversial, due
      partly to the lack of optimized and standardized preparation protocols. We used
      whole blood (WB) samples to optimize the preparation protocols for PRP, white
      blood cell-containing (W-PRP), platelet-concentrated plasma (PCP), and
      noncoagulating platelet-derived factor concentrate (PFC). PRP and W-PRP were most
      efficiently collected by 10 min centrifugation in a 15-mL conical tube at 230-270
      g and 70 g, respectively. To prepare PCP, platelets were precipitated by
      centrifugation of PRP at >2300 g, 90% of supernatant plasma was removed, and the
      platelets were resuspended. For preparation of noncoagulating PFC, the
      supernatant was replaced with one-tenth volume of saline, followed by platelet
      activation with thrombin. Platelet (before activation) and platelet-derived
      growth factor (PDGF)-BB (after activation) concentrations in PCP were
      approximately 20 times greater than those in WB, whereas PFC contained a 20-times
      greater concentration of platelets before platelet activation and a 50-times
      greater concentration of PDGF-BB without formation of a fibrin gel after platelet
      activation than WB. Surprisingly, total PDGF-BB content in the PFC was twice that
      of activated WB, which suggested that a substantial portion of the PDGF-BB became
      trapped in the fibrin glue, and replacement of plasma with saline is crucial for
      maximization of platelet-derived factors. As an anticoagulant, ethylene di-amine
      tetra-acetic acid disodium inhibited platelet aggregation more efficiently than
      acid citrate dextrose solution, resulting in higher nonaggregated platelet yield
      and final PDGF-BB content. These results increase our understanding of how to
      optimize and standardize preparation of platelet-derived factors at maximum
      concentrations.

PMID- 21951066
TI  - The oxysterol 27-hydroxycholesterol regulates alpha-synuclein and tyrosine
      hydroxylase expression levels in human neuroblastoma cells through modulation of
      liver X receptors and estrogen receptors--relevance to Parkinson's disease.
AB  - Loss of dopaminergic neurons and alpha-synuclein accumulation are the two major
      pathological hallmarks of Parkinson's disease. Currently, the mechanisms
      governing depletion of dopamine content and alpha-synuclein accumulation are not
      well understood. We showed that the oxysterol 27-hydroxycholesterol (27-OHC)
      reduces the expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in
      dopamine synthesis, and increases alpha-synuclein levels in SH-SY5Y cells.
      However, the cellular mechanisms involved in 27-OHC effects were not elucidated.
      In this study, we demonstrate that 27-OHC regulates TH and alpha-synuclein
      expression levels through the estrogen receptors (ER) and liver X receptors
      (LXR). We specifically show that inhibition of ERbeta mediates 27-OHC-induced
      decrease in TH expression, an effect reversed by the ER agonist estradiol. We
      also show that 27-OHC and the LXR agonist GW3965 increase alpha-synuclein while
      the LXR antagonist 5alpha-6alpha-epoxycholesterol-3-sulfate significantly
      attenuated the 27-OHC-induced increase in alpha-synuclein expression. We further
      demonstrate that LXRbeta positively regulates alpha-synuclein expression and 27
      OHC increases LXRbeta-mediated alpha-synuclein transcription. Our results
      demonstrate the involvement of two distinct pathways that are involved in the 27
      OHC regulation of TH and alpha-synuclein levels. Concomitant activation of ERbeta
      and inhibition of LXRbeta prevent 27-OHC effects and may therefore reduce the
      progression of Parkinson's disease by precluding TH reduction and alpha-synuclein
      accumulation.

PMID- 21951068
TI  - A simplified method for determining hiatal biometry.
AB  - INTRODUCTION:   The levator hiatus is the largest potential hernial portal in the
      human body. Its dimensions are measured in the axial plane and are strongly
      associated with female pelvic organ prolapse. We aimed to compare two commonly
      used methods for measuring hiatal dimensions. METHODS:   We performed offline
      analysis of 100 consecutive 4D ultrasound volume datasets of women seen in a
      tertiary urogynecological clinic. Hiatal measurements were obtained in sectional
      planes (SP, Method A) and rendered volumes of 1-2 cm thickness (RV, Method B).
      RESULTS:   A test-retest series in 20 women showed similar repeatability for both
      methods, with an intraclass correlation (ICC) of 0.85 (CI 0.81-0.88) for Method A
      (SP) and of 0.88 (CI 0.85-0.9) for Method B (RV). Measurements taken from
      rendered volumes were generally lower than those taken in axial plane slices,
      reaching significance for area on Valsalva (P=0.005), sagittal diameter and area
      on pelvic floor contraction (P=0.009 and 0.044). Method B seemed more strongly
      associated with symptoms of prolapse than Method A (P=0.008 vs P=0.027).
      CONCLUSIONS:   We recommend that hiatal dimensions be measured in rendered
      volumes whenever possible because this method seems more valid and at least as
      repeatable. This is probably due to the fact that the plane of minimal hiatal
      dimensions is non-Euclidean, i.e., warped, which can be compensated for by
      measuring in a rendered volume of 1-2 cm thickness.

PMID- 21951069
TI  - Leptin, adiponectin and other adipokines in gestational diabetes mellitus and pre
      eclampsia.
AB  - Proteins secreted from adipocytes - so-called adipokines - influence metabolic
      and vascular function. Recent data suggest that various adipokines are
      dysregulated in gestational diabetes mellitus (GDM) and pre-eclampsia (PE) and
      might be of pathophysiological and prognostic significance in these complications
      of pregnancy. This review gives an overview on the regulation and pathophysiology
      of leptin and adiponectin in GDM and PE. Furthermore, data on novel adipokines
      including resistin, visfatin, retinol-binding protein 4 and vaspin are
      summarized.

PMID- 21951071
TI  - Comprehensive and full.

PMID- 21951070
TI  - Postharvest temperature influences volatile lactone production via regulation of
      acyl-CoA oxidases in peach fruit.
AB  - The biosynthesis of volatile compounds in plants is affected by environmental
      conditions. Lactones are considered to be peach-like aroma volatiles; however, no
      enzymes or genes associated with their biosynthesis have been characterized.
      White-fleshed (cv. Hujingmilu) and yellow-fleshed (cv. Jinxiu) melting peach
      (Prunus persica L. Batsch) fruit were used as materials in two successive seasons
      and responses measured to four different temperature treatments. Five major
      lactones accumulated during postharvest peach fruit ripening at 20  degrees C.
      Peach fruit at 5  degrees C, which induces chilling injury (CI), had the lowest
      lactone content during subsequent shelf life after removal, while 0  degrees C
      and a low-temperature conditioning (LTC) treatment alleviated development of CI
      and maintained significantly higher lactone contents. Expression of PpACX1 and
      activity of acyl-CoA oxidase (ACX) with C16-CoA tended to increase during
      postharvest ripening both at 20  degrees C and during shelf life after removal
      from cold storage when no CI was developed. There was a positive correlation
      between ACX and lactones in peach fruit postharvest. Changes in lactone
      production in response to temperatures are suggested to be a consequence of
      altered expression of PpACX1 and long-chain ACX activity.

PMID- 21951072
TI  - Comment on "Understanding the epitaxial growth of Se(x)Te(y)@Te core-shell
      nanorods and the generation of periodic defects".

PMID- 21951075
TI  - Initial practice recommendations for teleneuropsychology.
AB  - Telemedicine refers to the use of electronic communications to deliver health
      related services from a distance, and is particularly useful in bringing
      specialty services to remote and/or underserved areas. Despite the increasing use
      of videoconference technology in psychology, there are very few guidelines to
      direct practitioners as to the ethical practice and utilization of telemedicine,
      and even fewer resources for practitioners of telecognitive assessment or
      teleneuropsychology. This paper seeks to outline several practical and ethical
      considerations that are relevant to the practice of telecognitive assessment and
      to assist practitioners in providing safe, ethical, and competent care to their
      patients by proposing some initial practice recommendations.

PMID- 21951077
TI  - Morphology-dependent voltage sensitivity of a gold nanostructure.
AB  - Gold nanostructures of various morphologies, including nanospheres, nanorods,
      nanoprisms, and thin films, were immobilized on ITO-coated coverslips in order to
      investigate the response of their scattering to potential. Shifts in the plasmon
      band obtained by potential-modulated spectroscopic imaging indicated that the
      voltage sensitivity of the gold nanostructure is dependent on its morphology,
      with nanospheres exhibiting the lowest sensitivity and ultrathin gold films
      exhibiting the highest. The effects of potential on gold nanoparticles are in
      qualitative agreement with Mie and Gans' theories in which the shift of the gold
      plasma frequency is due to the charging-discharging of the nanoparticles.

PMID- 21951076
TI  - Postoperative inotrope and vasopressor use following CABG: outcome data from the
      CAPS-care study.
AB  - BACKGROUND/AIM: Limited clinical data exist to guide practice patterns and
      evidence-based use of inotropes and vasopressors following coronary artery bypass
      grafting (CABG). METHODS: Contemporary Analysis of Perioperative Cardiovascular
      Surgical Care (CAPS-Care) collected detailed perioperative data from 2390 CABG
      patients between 2004 and 2005 at 55 U.S. hospitals. High-risk elective or urgent
      CABG patients were eligible for inclusion. We stratified participating hospitals
      into high, medium, and low tertiles of inotrope use. Hospital-level outcomes were
      compared before and after risk adjustment for baseline characteristics. RESULTS:
      Hospital-level risk-adjusted rates of any inotrope/vasopressor use varied from
      100% to 35%. Hospitals in the highest tertile of use had more patients with
      mitral regurgitation compared to medium- or low-use hospitals (p < 0.001), more
      previous cardiovascular interventions (p = 0.002), longer cardiopulmonary bypass
      (p < 0.001), longer cross-clamp times (p < 0.001), and required more transfusions
      (p = 0.001). Despite these differences, unadjusted outcomes were similar between
      high-, medium-, and low-use hospitals for operative mortality (4.5% vs. 5.3% vs.
      5.2%; p = 0.702), 30-day mortality (4.1% vs. 4.6% vs. 5.0%; p = 0.690),
      postoperative renal failure (7.2% vs. 9.2% vs. 6.6%; p = 0.142), atrial
      fibrillation (23.0% vs. 27.2% vs. 25.6%; p = 0.106), and acute limb ischemia
      (0.6% vs. 0.5% vs. 0.5%; p = 0.945). These similar outcomes persisted after risk
      adjustment: adjusted OR = 0.97 (95% CI [0.94, 1.00], p = 0.086) for operative
      mortality and adjusted OR = 1.00 (95% CI [0.96, 1.04], p = 0.974) for
      postoperative renal failure. CONCLUSION: While considerable variability is
      present among hospitals in inotrope use following CABG, observational comparison
      of outcomes did not distinguish a superior pattern; thus, randomized prospective
      data are needed to better guide clinical practice.

PMID- 21951086
TI  - Transformation of myxofibrosarcoma into myxoinflammatory fibroblastic sarcoma.

PMID- 21951087
TI  - Experimental endoscopic submucosal dissection training in a porcine model:
      learning experience of skilled Western endoscopists.
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) demands a new level of
      endoscopic skill in Europe. A 2-day workshop was set up for trainees to carry out
      five ESD each in order to obtain the skill level required to perform ESD in the
      stomach or rectum. This study describes: (i) the workshop setup; (ii) the
      participant's performance; and (iii) the training effect on post-workshop
      clinical ESD performance. METHODS: Eighteen very experienced European
      endoscopists participated in four half-day (4.5 h) training sessions, with
      everybody rotating daily through six separate training stations (two each with
      dual, hook, or hybrid knives) with expert tutors. One anesthetized piglet was
      used per station and session. After 1 year, the clinical ESD performance was
      surveyed to estimate the training effect of the workshop. RESULTS: Overall, 74
      ESD were performed, that is, 4.1 ESD per participant. On average ESD lasted 57
      min for 6 cm(2) specimens. We detected a 22% rate of perforation (16 of 74 ESD
      with perforations), mostly attributable to participants with less experience in
      ESD. Those who started clinical ESD within 1 year after the workshop performed
      144 clinical ESD (median 8 [0-20] per trainee) mostly in the stomach (40%) and
      large bowel (46%) with an acceptable rate of perforation (9.7%) and surgical
      repair (3.5%) without mortality or persistent morbidity. CONCLUSION: Intense
      skill training for ESD is needed to reduce the risk of perforation, as
      demonstrated by the results of this workshop. We show that experimental ESD
      training, however, enables skilled European endoscopists to perform ESD in
      standard locations with moderate risk of perforation during the clinical learning
      curve.

PMID- 21951088
TI  - Risk factors for bleeding after endoscopic submucosal dissection of gastric
      epithelial neoplasm.
AB  - BACKGROUND: Although endoscopic submucosal dissection (ESD) is standard therapy
      in Japan for gastric epithelial neoplasm, the complication rate is
      unsatisfactory, with postoperative bleeding as the major complication. The aim of
      the present study was to determine risk factors for post-ESD bleeding in patients
      with gastric epithelial neoplasm. PATIENTS AND METHODS: The study included 764
      patients in whom 924 gastric epithelial neoplasms were resected endoscopically
      between June 2005 and December 2009: the period during which preventative
      coagulation for all exposed vessels on the artificial ulcer with hemostatic
      forceps upon completion of ESD was performed routinely. We analyzed the risk
      factors for bleeding after ESD in relation to the various clinical factors.
      RESULTS: The post-ESD bleeding rate was 3.0%. Dialysis (vs no dialysis, P =
      0.034), operation time >=75 min (vs <75 min, P = 0.012) and poor control of
      bleeding during ESD (vs good control, P = 0.014) were significantly related to
      post-ESD bleeding. Poor control of bleeding during ESD (vs good control; P =
      0.04) and operation time >=75 min (vs <75 min; P = 0.012) were significantly
      related to bleeding after second-look endoscopy. CONCLUSIONS: Patients at high
      risk for post-ESD bleeding in gastric epithelial neoplasm were those undergoing
      dialysis, those in whom operation time was >=75 min, and those in whom bleeding
      during ESD was poorly controlled. The latter two are risk factors for bleeding
      even after second-look endoscopy.

PMID- 21951089
TI  - Influential factors in procedure time of endoscopic submucosal dissection for
      gastric cancer with fibrotic change.
AB  - BACKGROUND: Factors correlating with the technical difficulty of endoscopic
      submucosal dissection (ESD) for early gastric cancer (EGC) are still unclear. EGC
      coexisting with fibrosis inside lesions has been a common therapeutic indication
      for ESD. The aim of this study was to clarify the most important factor related
      to difficult ESD for EGC. PATIENTS AND METHODS: Fifty-six patients (49 male and
      seven female, median age 66 years) who received ESD at a single institute for EGC
      with fibrosis in the resected lesion were selected. Various clinicopathological
      factors, including the histological findings of fibrotic changes within the
      cancer area in the resected specimen, were evaluated statistically for
      correlation with ESD procedure time. RESULTS:   Univariate linear regression
      analysis with logarithmic ESD procedure time revealed the upper-third portion of
      lesion in the stomach (P = 0.02), histological classification of dense fibrosis
      (ulcer/ulcer scar-III/IV) within EGC (P < 0.001), and presence of peptic ulcer
      other than EGC (P = 0.04). Areas of the resected specimen (P < 0.001) and
      fibrosis (P < 0.001) were significant factors related to prolonged operation
      times. Multivariate analysis demonstrated that the upper-third portion of lesion
      (P = 0.007), ulcer/ulcer scar-III/IV findings (P = 0.006), and area of resected
      specimen (P = 0.006) were significant independent factors influencing ESD
      procedure time. CONCLUSION: Histological findings of fibrotic changes coexisting
      with EGC are closely related to technical difficulty in ESD as well as the
      location of tumors. Preoperative precise evaluation of fibrotic changes within
      EGC may be helpful to predict a technical difficulty in ESD.

PMID- 21951090
TI  - Small bowel lesions detected with wireless capsule endoscopy in patients with
      active ulcerative colitis and with post-proctocolectomy.
AB  - BACKGROUND: Although rare, duodenal lesions have been reported in association
      with ulcerative colitis (UC); however, there have been very few reports on small
      bowel lesions, and many aspects of their pathology and frequency remain unknown.
      This study determined whether small bowel lesions are present in UC by using
      wireless capsule endoscopy (WCE). PATIENTS AND METHODS: WCE was performed on 20
      patients with active UC and 10 who had undergone proctocolectomy. RESULTS: Small
      bowel lesions (e.g. edema or ulcers) were observed in 11 of the 30 patients
      (36.6%): in eight (40%) of the 20 patients with active UC and in three (33.3%) of
      the 10 post-proctocolectomy patients. Ulcers that extended over a long segment or
      whole tertile of the small bowel were observed in five patients, and the disease
      type was extensive colitis in three of these and pouchitis in the other two. Age
      at onset was significantly lower in the 20 active UC patients that had small
      bowel lesions. CONCLUSION: WCE revealed the presence of ulcers that extended over
      a long segment or a whole tertile in the small bowel in active extensive colitis
      and pouchitis. In future, it will be necessary to assess the clinical
      significance of small bowel lesions in UC in detail.

PMID- 21951092
TI  - Non-alcoholic steatohepatitis mimicking liver metastasis in obesity surgery.
AB  - We describe a case of non-alcoholic steatohepatitis detected incidentally during
      laparoscopic Roux-en-Y gastric bypass (LRYGBP). A 51-year-old female patient was
      scheduled for elective LRYGBP. Her weight was 144.9 kg and her body mass index
      was 56. Liver function tests showed mild elevation in alanine transaminase. The
      patient had a history of hypertension and insulin resistance and had no history
      of alcohol abuse. During LRYGBP, the gross appearance of the liver resembled
      metastatic lesions but the histology confirmed the diagnosis of non-alcoholic
      steatohepatitis. The appearance of the liver necessitated taking biopsies, which
      showed Von Meyenburg complexes and moderate macrovesicular steatosis. This
      patient made an uneventful recovery and was discharged 2 days postoperatively.

PMID- 21951091
TI  - Results of a Japanese multicenter, randomized trial of endoscopic stenting for
      non-resectable pancreatic head cancer (JM-test): Covered Wallstent versus
      DoubleLayer stent.
AB  - BACKGROUND: No study has compared covered metallic stents with Tannenbaum stents.
      We evaluated the efficacy of the DoubleLayer stent (DLS) and Covered Wallstent
      (CWS) in patients with pancreatic head cancer (PHC). PATIENTS & METHODS: This was
      a multicenter, prospective randomized study. Between October 2005 and December
      2007, we enrolled 113 patients (58 DLS, 55 CWS) with unresectable PHC with distal
      biliary obstructions and observed them for at least 6 months. RESULTS: No
      significant difference in patient survival was found between groups, with a
      median survival of 231 and 248 days in the DLS and CWS groups, respectively. The
      cumulative stent patency was significantly higher (P = 0.0072) in the CWS group.
      The respective mean and median stent patency was 202 and 133 days in the DLS
      group and 285 and 419 days in the CWS group. The incidence of DLS occlusion
      (53.5%) was significantly higher than that of CWS (23.6%; P = 0.0019). The
      respective causes of occlusion were tumor overgrowth (0, 1), ingrowth (0, 2),
      sludge (24, 2), food impaction (3, 5), kinking bile duct (2, 0), and other (2,
      3). Other complications were cholecystitis (0, 4), pancreatitis (0, 1), migration
      (1, 5), liver abscess (2, 0), and other (1, 2). No significant difference in the
      incidence of complications between groups was observed. CONCLUSION: CWS had
      significantly longer patency than DLS for the management of PHC with obstructive
      jaundice. The incidence of complications other than stent occlusion was higher in
      CWS, but this difference did not reach significance.

PMID- 21951093
TI  - Endoscopically treated Cronkhite-Canada syndrome associated with minute
      intramucosal gastric cancer: an analysis of molecular pathology.
AB  - There have been no reports of Cronkhite-Canada syndrome (CCS) associated gastric
      cancer resected with endoscopy because it is very difficult to identify small
      cancers that are candidates for endoscopic resection. We report a case of CCS
      with gastric cancer treated with endoscopic submucosal dissection, and we
      evaluate the molecular pathological analysis of malignant transformation in
      patients with CCS. A 74-year-old man had an advanced rectal cancer and
      gastrointestinal polyposis after presenting with hypoproteinemia, partial hair
      loss and atrophic nails as well as hyperpigmentation on the hands. He was
      diagnosed as having CCS. On upper endoscopy, a 7 mm discolored polyp with an
      irregular microvascular pattern revealed by magnified narrow-band imaging (NBI)
      was identified in gastric diffuse CCS polyposis. This lesion was treated with
      endoscopic submucosal dissection and diagnosed as a flat, elevated-type, mucosal
      well-differentiated tubular adenocarcinoma without lymphatic or venous
      infiltration, and with tumor-free margins. Microsatellite instability was
      detected in both the cancer and the surrounding CCS polyps. Mucin-histochemical
      analysis of the cancer area showed the complete intestinal type, and thus may
      have differentiated the CCS polyps from that of the common gastric hyperplastic
      polyps. This case illustrates that a clue to detecting small cancers may be to
      look for the discolored lesion among reddish CCS polyposis and thereafter to
      observe the irregular vascular pattern with NBI endoscopy. From the viewpoint of
      genetic alterations, patients with CCS polyps are considered to be at high risk
      for developing gastric cancer, and therefore careful follow-up examinations are
      necessary for the early detection of malignancies.

PMID- 21951094
TI  - Re: pseudomembranous colitis complicating ulcerative colitis.

PMID- 21951095
TI  - Successful endoscopic mucosal resection of a hyperplastic polyp in a hemophilia A
      patient.

PMID- 21951096
TI  - Endoscopic hemostasis using N-butyl-2-cyanoacrylate for massive gastric bleeding
      during endoscopic transgastric drainage of a pancreatic pseudocyst.

PMID- 21951097
TI  - Regression of multiple duodenal hyperplastic polyps following Helicobacter pylori
      eradication.

PMID- 21951098
TI  - Advanced colorectal cancer with double-hump camel-like appearance.

PMID- 21951099
TI  - The 'Loop Clip' is useful for closing large mucosal defects after colorectal
      endoscopic submucosal dissection: a preliminary clinical study.

PMID- 21951102
TI  - Live-cell-permeant thiophene fluorophores and cell-mediated formation of
      fluorescent fibrils.
AB  - In our search for thiophene fluorophores that can  overcome the limits of
      currently available organic dyes in live-cell staining, we synthesized
      biocompatible dithienothiophene-S,S-dioxide derivatives (DTTOs) that were
      spontaneously taken up by live mouse embryonic fibroblasts and HeLa cells. Upon
      treatment with DTTOs, the cells secreted nanostructured fluorescent fibrils,
      while cell viability remained unaltered. Comparison with the behavior of other
      cell-permeant, newly synthesized thiophene fluorophores showed that the formation
      of fluorescent fibrils was peculiar to DTTO dyes. Laser scanning confocal
      microscopy of the fluorescent fibrils showed that most of them were characterized
      by helical supramolecular organization. Electrophoretic analysis and theoretical
      calculations suggested that the DTTOs were selectively recognized by the HyPro
      component of procollagen polypeptide chains and incorporated through the
      formation of multiple H-bondings.

PMID- 21951103
TI  - Melatonin suppresses acrolein-induced IL-8 production in human pulmonary
      fibroblasts.
AB  - Cigarette smoke (CS) causes harmful alterations in the lungs and airway
      structures and functions that characterize chronic obstructive pulmonary disease
      (COPD). In addition to COPD, active cigarette smoking causes other respiratory
      diseases and diminishes health status. Furthermore, recent studies show that,
      alpha, beta-unsaturated aldehyde acrolein in CS induces the production of
      interleukin (IL)-8, which is known to be related to bronchitis, rhinitis,
      pulmonary fibrosis, and asthma. In addition, lung and pulmonary fibroblasts
      secrete IL-8, which has a chemotactic effect on leukocytes, and which in turn,
      play a critical role in lung inflammation. On the other hand, melatonin regulates
      circadian rhythm homeostasis in humans and has many other effects, which include
      antioxidant and anti-inflammatory effects, as demonstrated by the reduced
      expressions of iNOS, IL-1beta, and IL-6 and increased glutathione (GSH) and
      superoxide dismutase activities. In this study, we investigated whether melatonin
      suppresses acrolein-induced IL-8 secretion in human pulmonary fibroblasts (HPFs).
      It was found that acrolein-induced IL-8 production was accompanied by increased
      levels of phosphorylation of Akt and extracellular signal-regulated kinases
      (ERK1/2) in HPFs, and that melatonin suppressed IL-8 production in HPFs. These
      results suggest that melatonin suppresses acrolein-induced IL-8 production via
      ERK1/2 and phosphatidylinositol 3-kinase (PI3K)/Akt signal inhibition in HPFs.

PMID- 21951104
TI  - Skin perfusion pressure is useful for evaluating digital ulcer caused by systemic
      sclerosis.

PMID- 21951105
TI  - Health-related quality of life, work productivity and health care resource use
      associated with constipation predominant irritable bowel syndrome.
AB  - OBJECTIVES: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder.
      Prevalence estimates of IBS vary widely, from 10 to 15%, in the U.S. However, few
      studies have examined constipation predominant IBS (IBS-C), a subtype of IBS. The
      aim of this study was to assess the effect of IBS-C on health-related quality of
      life (HRQOL), work productivity and activity impairment, and health care resource
      use. METHODS: Using data from the 2007 U.S. National Health and Wellness Survey,
      IBS-C patients (n = 789) were compared to a propensity-score matched comparison
      group (n = 789). Differences between the groups were examined on HRQOL (SF-12v2),
      work productivity and activity impairment (WPAI questionnaire), and self-reported
      resource use in the last 6 months. RESULTS: Patients with IBS-C reported
      significantly lower levels of HRQOL (physical component summary score: 41.55 [95%
      CI: 40.72-42.37] versus 44.49 [95% CI: 43.67-45.31]; mental component summary
      score: 40.58 [95% CI: 39.75-41.40] vs. 45.87 [95% CI: 45.04-46.70]) and
      significantly higher mean levels of presenteeism (31.72% [95% CI: 28.25%-35.61%]
      vs. 21.43% [95% CI: 19.03%-24.15%]), overall work impairment (35.54% [95% CI:
      31.76%-39.76%] vs. 25.29% [95% CI: 22.59%-28.30%]), and activity impairment
      (45.78% [95% CI: 43.08%-48.66%] vs. 33.03% [95% CI: 31.08%-35.11%]) than matched
      comparators (all P values < 0.01). Patients with IBS-C reported significantly
      more provider visits (8.07 [95% CI: 7.38-8.82] vs. 5.55 [95% CI: 5.07-6.08]) and
      emergency room visits (0.57 [95% CI: 0.46-0.70] vs. 0.36 [95% CI: 0.29-0.45]) in
      the past 6 months (all Ps < 0.01). No statistically significant differences
      between the groups were observed in absenteeism or the number of the days
      hospitalized. CONCLUSIONS: IBS-C was associated with poorer HRQOL, greater work
      productivity loss and activity impairment, and greater healthcare resource use.
      Limitations include the study's cross-sectional design and its self-reported
      nature. Nevertheless, improved management of IBS-C may reduce the humanistic and
      economic burden of the condition and benefit patients, employers, and the
      healthcare system.

PMID- 21951107
TI  - Reaction products and kinetics of the reaction of NO2 with gamma-Fe2O3.
AB  - The reaction of NO(2) with Fe(2)O(3) has relevance for both atmospheric chemistry
      and catalysis. Most studies have focused on hematite, alpha-Fe(2)O(3), as it is
      the thermodynamic stable state of iron oxide; however, other forms of Fe(2)O(3)
      naturally occur and may have different chemistries. In this study, we have
      investigated the reaction products and kinetics for NO(2) reacting with gamma
      Fe(2)O(3) powder using diffuse reflectance infrared Fourier transform
      spectroscopy and compared the results to those of previous studies of NO(2)
      reacting with alpha-Fe(2)O(3). Both alpha- and gamma-Fe(2)O(3) produce surface
      bound nitrate at the pressures examined in this study (24-212 mTorr); surface
      bound nitrite products are observed at all pressures for gamma-Fe(2)O(3) whereas
      nitrite was only observed on alpha-Fe(2)O(3) at lower pressures. Surface-bound
      NO(+) and Fe-NO products are observed on gamma-Fe(2)O(3), which have not been
      observed with alpha-Fe(2)O(3). The reaction kinetics show a first-order
      dependence on NO(2) pressure and this is used to support the hypothesis of
      unimolecular reaction of adsorbed NO(2) with the gamma-Fe(2)O(3) surface as the
      slow step in the reaction mechanism. The difference in product formation between
      NO(2) reacting with gamma-Fe(2)O(3) and previous studies of alpha-Fe(2)O(3)
      illustrate the fact that care must be taken in generalizing reactivity of
      different polymorphs.

PMID- 21951106
TI  - Analytical solution for drainage and recession from an unconfined aquifer.
AB  - One-dimensional transient groundwater flow from a divide to a river in an
      unconfined aquifer described by the Boussinesq equation was studied. We derived
      the analytical solution for the water table recession and drainage change process
      described with a linearized Boussinesq equation with a physically based initial
      condition. A method for determining the average water table in the solutions was
      proposed. It is shown that the solution derived in the form of infinite series
      can be well approximated with the simplified solution which contains only the
      leading term of the original solution. The solution and their simplification can
      be easily evaluated and used by others to study the groundwater flow problems,
      such as drainage and base flow estimation, in an unconfined aquifer.

PMID- 21951108
TI  - Preexisting mitral valve prosthesis in patients undergoing left ventricular
      assist device implantation.
AB  - Experience with patients undergoing left ventricular assist device (LVAD)
      implantation with preexisting mitral valve prostheses is limited. Patients with
      mechanical heart valves might have an increased risk of thromboembolism; in
      patients with biologic valves, there might be a risk of structural deterioration
      of the leaflets. Out of 597 patients supported with a LVAD system between 2000
      and 2009, 18 patients had mitral valve surgery prior to implantation. We excluded
      all patients below 18 years of age, those with postcardiotomy failure, and
      patients who had had mitral valve reconstruction. Only 1% of the studied patient
      population (n= 6) had mitral valve replacement. The mitral valve implantation has
      been performed 7.4 +/- 9.4 years prior to LVAD insertion. None of the valves (one
      biologic, five mechanical) were exchanged or explanted. LVAD implantation was
      done either with left lateral thoracotomy (n= 5) or with midline resternotomy (n=
      1). Temporary right ventricular assist device support was necessary in one case
      (16.6%); 30-day mortality was 16.6% (n= 1). Median support time was 14 +/- 15
      months. Two patients received heart transplantation after 6 and 26 months on the
      device; four patients died on mechanical circulatory support after 1, 2, 5, and
      40 months. No valve or pump thrombosis or other clinically relevant
      thromboembolic events were observed. Only a small number of patients (1%) had a
      preexisting mitral valve prosthesis prior to LVAD implantation. No severe adverse
      events were observed when the prosthesis was left in place. Attention should be
      paid to the anticoagulation regime.

PMID- 21951109
TI  - Axonal regeneration and neuroinflammation: roles for the translocator protein 18
      kDa.
AB  - After a traumatic injury of the nervous system or in the course of a
      neurodegenerative disease, the speed of axonal regeneration and the control of
      the inflammatory response are fundamental parameters of functional recovery.
      Spontaneous regeneration takes place in the peripheral nervous system, although
      the process is slow and often incomplete. There is currently no efficient
      treatment for enhancing axonal regeneration, including elongation speed and
      functional reinnervation. Ligands of the translocator protein 18 kDa (TSPO) are
      currently under investigation as therapeutic means for promoting neuroprotection,
      accelerating axonal regeneration and modulating inflammation. The mechanisms of
      action of TSPO ligands involve the regulation of mitochondrial activity and the
      stimulation of steroid biosynthesis. In the peripheral nervous system, TSPO
      expression is strongly up-regulated after injury, primarily in Schwann cells and
      macrophages, but also in neurones. Its levels return to low control values when
      nerve regeneration is completed, strongly supporting an important role in
      regenerative processes. We have demonstrated a role for the benzoxazine etifoxine
      in promoting axonal regeneration in the lesioned rat sciatic nerve, either after
      freeze-injury or complete transection. Etifoxine is already clinically approved
      for the treatment of anxiety disorders (Stresam((r)) , Biocodex, Gentilly,
      France). Daily treatment with etifoxine resulted in a two-fold acceleration in
      axonal regeneration, as well as in a marked improvement of both the speed and
      quality of functional recovery. The neuroregenerative effects of etifoxine are
      likely to be mediated by TSPO, and they may involve an increased synthesis of
      pregnenolone and its metabolites, such as progesterone. After freeze-injury of
      the sciatic nerve, administration of etifoxine also strongly reduced the number
      of activated macrophages and decreased the production of the inflammatory
      cytokines tumour necrosis factor-alpha and interleukin-1beta. Thus, this drug
      offers promise for the treatment of peripheral nerve injuries and axonal
      neuropathies. It may also be used as a lead compound in the development of new
      TSPO-based neuroprotective approaches.

PMID- 21951110
TI  - Rathke's cleft cysts.
AB  - Rathke's cleft cysts (RCCs) are benign, sellar and/or suprasellar lesions
      originating from the remnants of Rathke's pouch. Although a common finding in
      routine autopsies (12-33% of normal pituitary glands), symptomatic cases are rare
      and comprise 5-15% of all surgically resected sellar lesions. Small, asymptomatic
      RCC do not require surgical intervention, and their natural history is not clear.
      In series of nonoperated presumed RCCs, 26-94% did not progress during follow-up
      periods up to 9 years. In symptomatic ones, surgery is indicated, aiming to drain
      the cyst content and safely remove as much of the capsule as possible. Following
      surgical intervention, headaches and visual field defects improve or resolve in a
      significant number of patients (40-100% and 33-100%, respectively) and partial
      hypopituitarism recovers in 14-50%. Data on relapse rates published in the last
      15 years are based on variable follow-up periods and show wide variation (between
      0% and 33%). The lowest relapse rates have been described in reports with
      relatively short mean observation periods (<3 years), whereas in those with
      longer follow-up the relapse rates increase. Most of the relapses occur within 5
      6 years, suggesting that follow-up is required for at least 5 years after
      surgery. Risk factors for relapse include the presence of squamous metaplasia in
      the cyst wall, cyst size and the presence of inflammation. Long-term sufficiently
      powered studies aiming to clarify the natural history of asymptomatic RCCs and of
      those relapsing postoperatively are required.

PMID- 21951111
TI  - Liver hydatidosis in the present decade.

PMID- 21951112
TI  - Profile of patients with hepatic hydatid disease not treated surgically.
AB  - BACKGROUND: hepatic hydatid disease (HHD) is still an important health problem in
      certain areas of Spain where it is endemic. The treatment of HHD is usually
      surgical but certain patients are found to be ineligible after assessment for
      surgery (asymptomatic disease, comorbidity, patient refusal, or other). MATERIAL
      AND METHODS: description of patients assessed in the Department of Surgery for
      hepatic hydatid disease. RESULTS: in a group of 70 patients with HHD, 27 patients
      were not treated surgically (mean age: 72.7 years [range: 47-97], 14 women
      [51.8%]). The number of cysts presented by these patients was 33, with 1.22
      cyst/patient (range: 1-4). The cyst size was 5.5 cm (range: 2.1-12.5 cm). The
      cysts, according to the WHO classification, were CE1: 3 patients, CE3B: 5
      patients, CE4: 10 patients and CE5: 9 patients. The form of presentation was:
      symptomatic in 9 patients, although only 6 were attributable to HHD (22%) and
      asymptomatic in 18 patients. In these cases, imaging was performed for study of
      tumor extension in 6 patients and diverse medical reasons in 12. Only two
      therapeutic interventions were performed: endoscopic retrograde
      cholangiopancreatography (ERCP) with insertion of a bile duct stent, and puncture
      aspiration-injection-re-aspiration (PAIR), both in patients who did not wish to
      undergo surgery.Ten patients had surgical indications: CE1 (3 patients), CE3B (5
      patients), CE4 (1 patient), and CE5 (1 patient). The reasons why the patients did
      not undergo surgical treatment were: refusal (9 patients) and advanced neoplasm
      (1 patient). Surgery was judged necessary in 5 patients. In the mean follow-up
      period of 17 months (range: 1-37), no surgery was performed. CONCLUSIONS: there
      were various causes for not performing surgical intervention of HHD after medical
      evaluation: asymptomatic patients, older patients, patients with multiple
      pathologies and oncologic patients. Usually, they were patients who voluntarily
      chose not to undergo surgery.

PMID- 21951113
TI  - Anti-tissue transglutaminase antibodies (IgA and IgG) in both Crohn's disease and
      autoimmune diabetes.
AB  - OBJECTIVE: a strong association has been observed between celiac disease,
      generally its silent clinical form, and autoimmune disorders. A potential
      correlation with inflammatory bowel disease has also been suggested. Anti-tissue
      transglutaminase antibodies have been detected in Crohn's disease. We
      investigated the prevalence of celiac disease in patients with autoimmune
      diabetes and in Crohn's disease patients and also evaluated the correlation
      between anti-transglutaminase antibody positivity and the clinical status of
      these diseases. METHODS: anti-tissue transglutaminase and anti-endomysium
      antibodies were assessed by enzyme-linked immunosorbent assay and indirect
      immunofluorescence, respectively. Upper digestive endoscopy and duodenal biopsy
      were indicated for cases with positive serology. RESULTS: anti-transglutaminase
      antibodies were detected in five diabetic patients (prevalence of 11.1%), only
      one serum sample was positive for IgG isotypes. Nine of thirty-three patients
      with Crohn's disease had low positive levels for IgA anti-transglutaminase.
      Antiendomysium antibodies were detected only in celiac patients. Celiac disease
      was confirmed in all diabetic patients submitted to duodenal biopsies who
      presented both anti-transglutaminase and anti-endomisyum antibodies positivity.
      In Crohn's disease, its clinical status and the diagnosis of celiac disease were
      not associated with positiveanti-transglutaminase result. CONCLUSIONS: the
      prevalence of celiac disease was high in diabetic patients. Anti-tissue
      transglutaminase antibodies were sensitive and specific markers of celiac disease
      in this diabetic group, while these antibodies were of limited value for celiac
      disease screening in patients with Crohn's disease.

PMID- 21951114
TI  - Colorectal cancer and its delayed diagnosis: have we improved in the past 25
      years?
AB  - OBJECTIVE: to determine the current delay in diagnosing colorectal cancer (CRC)
      and establish whether there has been any improvement in the past 25 years in the
      same healthcare setting using the same methods. PATIENTS AND METHOD: 152 patients
      undergoing surgery at our unit were personally interviewed during their hospital
      stay to determine the delay incurred for the diagnosis and treatment of their
      CRC. SPSS software was used for univariate and multivariate analysis of the data
      obtained. RESULTS: the study population was comprised of 152 patients of mean age
      71 years (SD 10; range 36 to 90 years), 82 men and 70 women (53.9 and 46.1%
      respectively; p > 0.05). The diagnostic delay for CRC at our unit currently runs
      at 7.28 months despite the fact that in 58% of patients the disease produced
      obvious symptoms such as rectal bleeding. Although this delay in diagnosis is
      reduced over that observed 25 years ago, the difference is statistically not
      significant in terms of both doctor-attributed or patient-attributed delay
      (doctor-attributed delay was 3.28 months in 1985 versus 1.89 at present and
      patient-attributed delay was 3.18 months versus today's 2.75; p > 0.05). Unlike
      the situation 25 years ago, no link was detected between diagnostic delay and
      tumor stage. Paradoxically, stage D disease was diagnosed earlier (at 5.71
      months) than stage A disease (at 11.16 months) (p < 0.05). CONCLUSION: the
      diagnostic delay for CRC at our centre is 7.28 months. This delay is excessive
      for a disease that produces evident symptoms in 90% of patients. Over the last 25
      years little improvement has been noted in the overall delay in diagnosing CRC,
      al though the delay attributed to the care provider has significantly improved.
      No relationship was detected between diagnostic delay and disease stage upon
      diagnosis. We feel the high prevalence of CRC, the failure of campaigns to
      increase awareness of early symptoms and no real improvement in its prognosis
      justify the introduction of large-scale colonoscopy screening for this disease.

PMID- 21951115
TI  - Diagnostic accuracy and therapeutic impact of endoscopic ultrasonography in
      patients with intermediate suspicion of choledocholithiasis and absence of
      findings in magnetic resonance cholangiography.
AB  - BACKGROUND: endoscopic ultrasonography (EUS) and magnetic resonance
      cholangiography (MRC) are the elective tests in the diagnosis of
      choledocholithiasis. MRC is best accepted by patients, but its sensitivity might
      decrease in the evaluation of microlithiasis. AIM: to evaluate the diagnostic
      accuracy and therapeutic impact of EUS in a prospective cohort of patients with
      intermediate suspicion of choledocolithiasis and no findings in MRC (normal MRC).
      MATERIAL AND METHODS: during a period of 24 months, all the patients with
      clinical intermediate suspicion of choledocholithiasis and normal MRC were
      included. Sensitivity, specificity, diagnostic accuracy, positive predictive
      value (PPV) and negative predictive value (NPV) of MRC and EUS were compared, and
      so their impact in the management of these patients. RESULTS: seventy six
      patients were evaluated (lithiasis in 30% of them). Sensitivity and diagnostic
      accuracy of EUS (100%, 92%) were significantly higher than MRC values (0%, 70%)
      (p < 0.05). EUS findings (suspicion of choledocholithiasis) favored a significant
      change in therapeutic attitude (therapeutic ERCP was performed) in 38% of the
      patients (in which MRC had ruled out the presence of choledocholithiasis, and so,
      ERCP had not been performed) (p < 0.05). CONCLUSIONS: EUS allows the diagnosis of
      lithiasis in approximately 1/3 of patients with intermediate suspicion of
      choledocholithiasis and normal MRC. EUS findings involve a significant change in
      the management of these patients; this supports the use of EUS in clinical
      practice.

PMID- 21951116
TI  - Hepatotoxicity in 2011--advancing resolutely.

PMID- 21951117
TI  - Intraductal papillary mucinous neoplasm.

PMID- 21951118
TI  - Spontaneous esophageal rupture (Boerhaave's syndrome). An uncommon image.

PMID- 21951119
TI  - Posterolateral Bochdalek diaphragmatic hernia in adults.
AB  - Bochdalek hernias (BHs) are produced in the posterolateral area of the diaphragm.
      They are generally congenital, appearing in childhood, but are also detected in
      asymptomatic adult patients seeking medical attention for other reasons. Computed
      tomography (CT) or magnetic resonance imaging (MRI) is used for the correct
      diagnosis of the hernia type and for its localization, facilitating its
      management and the choice of treatment. We describe three cases of Bochdalek
      hernia, two on the right side and one bilateral, which was larger on the right
      than left side. All of these hernias contained only omental fat. In one patient,
      the right kidney was adjacent to the diaphragmatic defect but remained within the
      abdomen. The patients showed no symptoms and were not surgically treated.
      Examination by multislice CT with the possibility of coronal and sagittal
      reconstruction should be considered the standard method for diagnosing this
      entity. MRI in T1 is highly valuable to evaluate fat-containing chest lesions.
      The incidental finding of BH in asymptomatic adults is increasing, thanks to the
      wider application of new imaging techniques.

PMID- 21951120
TI  - [Information for patients. Functional abdominal pain].

PMID- 21951121
TI  - Diagnosis, treatment and follow-up of gastric carcinoid tumors. Analysis of 14
      cases.

PMID- 21951122
TI  - Biliopleural fistula after radiofrecuency ablation of hepatocellular carcinoma.

PMID- 21951123
TI  - Spontaneous intramural gastric haematoma in an anticoagulated patient.

PMID- 21951124
TI  - Endosonographic diagnosis of aberrant right subclavian artery that leads to
      disphagia lusoria.

PMID- 21951125
TI  - Gastric volvulus associated with cardiac tamponade.

PMID- 21951126
TI  - NOD2/CARD15 gene mutations in patients with inflammatory bowel disease in
      Valladolid.

PMID- 21951127
TI  - Association between Lynch syndrome and renal carcinoma.

PMID- 21951129
TI  - Divalent metal vinylphosphonate layered materials: compositional variability,
      structural peculiarities, dehydration behavior, and photoluminescent properties.
AB  - A family of M-VP (M = Ni, Co, Cd, Mn, Zn, Fe, Cu, Pb; VP = vinylphosphonate) and
      M-PVP (M = Co, Cd; PVP = phenylvinylphosphonate) materials have been synthesized
      by hydrothermal methods and characterized by FT-IR, elemental analysis, and
      thermogravimetric analysis (TGA). Their structures were determined either by
      single crystal X-ray crystallography or from laboratory X-ray powder diffraction
      data. The crystal structure of some M-VP and M-PVP materials is two-dimensional
      (2D) layered, with the organic groups (vinyl or phenylvinyl) protruding into the
      interlamellar space. However, the Pb-VP and Cu-VP materials show dramatically
      different structural features. The porous, three-dimensional (3D) structure of Pb
      VP contains the Pb center in a pentagonal pyramid. A Cu-VP variant of the common
      2D layered structure shows a very peculiar structure. The structure of the
      material is 2D with the layers based upon three crystallographically distinct Cu
      atoms; an octahedrally coordinated Cu(2+) atom, a square planar Cu(2+) atom and a
      Cu(+) atom. The latter has an unusual co-ordination environment as it is 3
      coordinated to two oxygen atoms with the third bond across the double bond of the
      vinyl group. Metal-coordinated water loss was studied by TGA and
      thermodiffractometry. The rehydration of the anhydrous phases to give the initial
      phase takes place rapidly for Cd-PVP but it takes several days for Co-PVP. The M
      VP materials exhibit variable dehydration-rehydration behavior, with most of them
      losing crystallinity during the process.

PMID- 21951128
TI  - Long-term detection of fluorescently labeled human mesenchymal stem cell in vitro
      and in vivo by semi-automated microscopy.
AB  - The use of seeded scaffolds in regenerative medicine is limited by the low
      survival of transplanted mesenchymal stem cells (MSC). Current approaches aim at
      improving cell viability but require an adequate long-term detection of the
      transplanted cells. Unfortunately, commonly performed labeling techniques have
      not been validated for this purpose, and studies often reveal inconclusive
      results. Consequently, we intended to identify the most suitable method for long
      term detection of human MSC (hMSC) in vitro and in vivo. hMSC were labeled using
      the vital stainings PKH26 and carboxyfluorescein diacetate succinimidyl ester
      (CFDA-SE) as well as enhanced green fluorescent protein (eGFP) transduction.
      Metabolic activity and relative fluorescence intensity (RFI) were quantified in
      vitro over 21 days at 8 time points using standardized semi-automated microscopy
      and flow cytometry. In vivo, cell seeded scaffolds were subcutaneously implanted
      in nude mice, and RFI was analyzed over 42 days at 5 time points. In vitro, PKH26
      and CFDA-SE significantly reduced metabolic activity. RFI of both stainings
      significantly decreased after 1 day and further faded to <1% after 7 days. In
      contrast, labeling with eGFP showed no metabolic effect on hMSC, and no
      significant reduction of RFI over the total period of 21 days. In vivo, RFI of
      eGFP labeled cells reached a plateau phase after 21 days and displayed a 3.8-fold
      higher RFI compared with PKH26 and CFDA-SE on day 42 evaluated in 280 field of
      views per scaffold using three scaffolds for each labeling technique and time
      point. We conclude that PKH26 and CFDA-SE are unsuitable for long-term detection
      of hMSC. eGFP transduction, in turn, allows long-term detection of hMSC in vitro
      and in vivo. Our results suggest that eGFP is currently the best option among the
      fluorescent labeling techniques to follow the fate of transplanted hMSC.

PMID- 21951130
TI  - Venous thromboembolism following gynaecological surgery for suspected or
      confirmed malignancy.
AB  - BACKGROUND: Venous thromboembolism (VTE) is a serious complication following
      gynaecological surgery, with malignancy placing patients at an even greater risk.
      AIMS: To review the incidence of VTE following gynaecological surgery for
      suspected or confirmed malignancy with respect to prophylactic modalities and to
      assess the incidence and associated risk factors for bleeding complications.
      METHODS: A retrospective cohort study was undertaken between 2001 to 2006 on 1363
      women undergoing surgery for suspected or confirmed gynaecological malignancy.
      Data on demographic details, diagnosis, radiotherapy/chemotherapy treatment,
      operative details, and hospital length of stay (LOS), thromboprophylaxis, in
      hospital and 3-month readmission rates for deep vein thrombosis (DVT) and/or
      pulmonary embolism (PE) were collected. RESULTS: Median age was 54 years (IQR 44
      66) and hospital LOS 7 days (IQR 5-9). 51.6% had a new malignancy and 33.0%
      benign disease. All in-hospital VTE events (0.4%; 95% CI 0.2-1.0%) occurred in
      women with advanced malignancy. VTE rate was 1.5% (95% CI 1.0-2.3%) at 3 months.
      In-hospital and 3-month non fatal PE occurred in 0.4% (95% CI 0.2-0.9%) and 1.1%
      (95% CI 0.7-1.8%) respectively, with a fatal PE rate of 0.1% (95% CI 0.04-0.5%).
      Malignancy (OR 10.3; 95% CI 1.3-80.6; P = 0.026) and duration of surgery (OR 2.1;
      95% CI 1.4-3.2; P = 0.001) significantly increased bleeding risk. CONCLUSIONS: In
      hospital VTE risk is higher following gynaecological surgery for malignancy than
      for benign disease, despite the use of thromboprophylaxis. Given the higher non
      fatal PE rate after discharge and increasing trend towards shorter hospital LOS,
      extended prophylaxis in these patients should be considered.

PMID- 21951132
TI  - Lipocalin Q83 reveals a dual ligand binding mode with potential implications for
      the functions of siderocalins.
AB  - Siderocalins are particular lipocalins that participate in the innate immune
      response by interfering with bacterial siderophore-mediated iron uptake.
      Additionally, siderocalins are involved in several physiological and pathological
      processes such as inflammation, iron delivery, tissue differentiation, and cancer
      progression. Here we show that siderocalin Q83 displays an unexpected dual ligand
      binding mode as it can bind enterobactin and unsaturated fatty acids
      simultaneously. The solution structure of the siderocalin Q83 in complex with
      arachidonic acid and enterobactin reveals molecular details of this novel dual
      binding mode and the determinants of fatty acid binding specificity. Our results
      suggest that Q83 is a metabolic hub linking iron and fatty acid pathways. This
      unexpected coupling might contribute to the pleiotropic functions of
      siderocalins.

PMID- 21951131
TI  - L-tryptophan ethyl ester dilates small mesenteric arteries by inhibition of
      voltage-operated calcium channels in smooth muscle.
AB  - BACKGROUND AND PURPOSE: L-tryptophan (L-W) is a precursor of the vasoconstrictor,
      5-HT. However, acute administration of L-W ethyl ester (L-Wee) lowered blood
      pressure. The mechanism of action is unknown. This study compares the vascular
      effects of L-W and L-Wee in intact animals, isolated aortic rings, small
      mesenteric arteries (MA) and explores possible mechanisms by studies in vascular
      smooth muscle cells (VSMC) of MA. EXPERIMENTAL APPROACH: Effects of L-W or L-Wee
      (5-50 mg kg(-1) , i.v.) on mean arterial pressure (MAP) and heart rate (HR) were
      determined in male Sprague-Dawley rats. The effects of L-W and L-Wee on basal
      tone and of phenylephrine- or KCl-induced contractions of aortic and MA rings
      were assessed. Effects of L-Wee and L-W on voltage-operated calcium channels
      (VOCC) of VSMC of MA were also examined in patch-clamp studies. KEY RESULTS:
      Administration of L-Wee, but not L-W, evoked a rapid and transient dose-dependent
      decrease in MAP and HR. While both agents failed to affect basal tone, L-Wee
      decreased, concentration-dependently, (I(max) > 98%) tension responses to
      phenylephrine and KCl in an endothelium-independent manner in aorta (IC(50) 2 mM)
      and MA (IC(50) 17 uM). L-Wee evoked concentration-dependent inhibition of VOCC
      currents (IC(50) 12 uM; I(max) 90%) in VSMC of MA. CONCLUSIONS AND IMPLICATIONS:
      Esterified L-W (L-Wee), but not L-W, preferentially relaxed resistance vessels
      rather than conduit vessels. These effects were associated with blockade of VOCC
      by L-Wee. Our findings suggest that the falls in MAP and HR induced by L-Wee were
      due to blockade of VOCC by L-Wee.

PMID- 21951133
TI  - Current advances in intravascular administration of stem cells for neurological
      diseases: a new dose of rejuvenation injected.
AB  - Selection of the appropriate administration route is one of the critical steps in
      a successful therapeutic process. From its beginning, stem cell-based
      rejuvenation of the central nervous system has been based on intraparenchymal
      cell transplantation. However, a high invasiveness of the procedure and a focal
      cell delivery can not be justified for any pathological conditions. This review
      analyses, compares, and comments on observed differences between the
      intraparenchymal and intravascular administration route for neurological
      diseases. A special emphasis has been given to the reported obstacles and
      specific recommendations have been made. More significant success with
      intravascular delivery of stem cells for neurological diseases can be achieved
      with smaller cells, use of dilatators of lung vasculature, blocking of
      endothelial receptors, less aggressive pretreatment of cells, and
      permeabilization of the blood-brain barrier. If these requirements are met,
      intravascular administration represents one of the major options for delivery of
      stem cells to the aging brain, with obvious advantages over direct
      intraparenchymal injection.

PMID- 21951134
TI  - Exclusion of plastid nucleoids and ribosomes from stromules in tobacco and
      Arabidopsis.
AB  - Stromules are stroma-filled tubules that extend from the surface of plastids and
      allow the transfer of proteins as large as 550 kDa between interconnected
      plastids. The aim of the present study was to determine if plastid DNA or plastid
      ribosomes are able to enter stromules, potentially permitting the transfer of
      genetic information between plastids. Plastid DNA and ribosomes were marked with
      green fluorescent protein (GFP) fusions to LacI, the lac repressor, which binds
      to lacO-related sequences in plastid DNA, and to plastid ribosomal proteins Rpl1
      and Rps2, respectively. Fluorescence from GFP-LacI co-localised with plastid DNA
      in nucleoids in all tissues of transgenic tobacco (Nicotiana tabacum L.) examined
      and there was no indication of its presence in stromules, not even in hypocotyl
      epidermal cells, which contain abundant stromules. Fluorescence from Rpl1-GFP and
      Rps2-GFP was also observed in a punctate pattern in chloroplasts of tobacco and
      Arabidopsis [Arabidopsis thaliana (L.) Heynh.], and fluorescent stromules were
      not detected. Rpl1-GFP was shown to assemble into ribosomes and was co-localised
      with plastid DNA. In contrast, in hypocotyl epidermal cells of dark-grown
      Arabidopsis seedlings, fluorescence from Rpl1-GFP was more evenly distributed in
      plastids and was observed in stromules on a total of only four plastids (<0.02%
      of the plastids observed). These observations indicate that plastid DNA and
      plastid ribosomes do not routinely move into stromules in tobacco and
      Arabidopsis, and suggest that transfer of genetic information by this route is
      likely to be a very rare event, if it occurs at all.

PMID- 21951135
TI  - Adipose triglyceride lipase affects triacylglycerol metabolism at brain barriers.
AB  - Currently, little is known about the role of intracellular triacylglycerol (TAG)
      lipases in the brain. Adipose triglyceride lipase (ATGL) is encoded by the PNPLA2
      gene and catalyzes the rate-limiting step of lipolysis. In this study, we
      investigated the effects of ATGL deficiency on brain lipid metabolism in vivo
      using an established knock-out mouse model (ATGL-ko). A moderate decrease in TAG
      hydrolase activity detected in ATGL-ko versus wild-type brain tissue was
      accompanied by a 14-fold increase in TAG levels and an altered composition of TAG
      associated fatty acids in ATGL-ko brains. Oil Red O staining revealed a severe
      accumulation of neutral lipids associated to cerebrovascular cells and in
      distinct brain regions namely the ependymal cell layer and the choroid plexus
      along the ventricular system. In situ hybridization histochemistry identified
      ATGL mRNA expression in ependymal cells, the choroid plexus, pyramidal cells of
      the hippocampus, and the dentate gyrus. Our findings imply that ATGL is involved
      in brain fatty acid metabolism, particularly in regions mediating transport and
      exchange processes: the brain-CSF interface, the blood-CSF barrier, and the blood
      brain barrier.

PMID- 21951136
TI  - Non-fragrance allergens in specific cosmetic products.
AB  - OBJECTIVES: Reports about the nature of the ingredients responsible for allergic
      contact dermatitis caused by specific cosmetic products are scarce. METHODS:
      Between January 2000 and December 2010, the specific cosmetic products having
      caused allergic contact dermatitis, as well as the individual allergenic cosmetic
      ingredients present in them, were recorded by use of a standardized form.
      RESULTS: Among 11 different categories of cosmetic product, skin care products,
      followed by hair care and body-cleansing products, were most often involved. The
      presence of the allergenic ingredient(s) in a specific cosmetic product was
      confirmed according to the ingredient label in 959 of 1448 records. Six hundred
      and twenty-one of 959 concerned non-fragrance components, preservatives being
      responsible for 58% of them. Reactions to formaldehyde and formaldehyde-releasers
      were most often correlated with body-cleansing products, particularly 2-bromo-2
      nitropropane-1,3-diol and skin care products. They were followed by the
      methylchloroisothiazolinone/methylisothiazolinone mixture, most frequently found
      as allergens in hair care and intimate hygiene products, and facial cleansers (in
      the last category together with diazolidinyl urea). Octocrylene was by far the
      most frequent (photo)allergen in sun care products. CONCLUSIONS: This study
      provides information on the presence and frequency of allergens in specific
      causal cosmetic products.

PMID- 21951137
TI  - Fibrin sealant effects on the ilioinguinal nerve.
AB  - BACKGROUND: Chronic pain after mesh repair for inguinal hernia may be related to
      the trauma to the regional nerves by direct compression with sutures, staples, or
      tacks during mesh fixation. Fibrin sealant (FS) has been recommended to eliminate
      this risk. In this experimental study, the effects of FS on the ilioinguinal
      nerve when a mesh was applied was searched. MATERIALS AND METHODS: Fifteen New
      Zealand rabbits were used in three groups. In Group 1, a 2*1 cm, standard
      monofilament, pure polypropylene mesh was laid over ilioinguinal nerve. In Group
      2, 0.5 ml FS was applied on the nerve without using an onlay mesh. In Group 3, a
      2*1 cm mesh was laid onlay and secured with 0.5 ml FS with no fixating suture.
      Three months after surgery bilateral nerve samples were taken from the contiguous
      nerve segment for microscopic study. RESULTS: Group 1 showed prominent findings
      with regard to all parameters. There were significant differences between Group 1
      and Group 2 in respect of fibrosis, lymphocyte, and edema scores, and foreignbody
      reaction. The values of Group 3, where the mesh was secured by the application of
      FS with no suture, were roughly placed in between Group 1 and Group 2. Prominent
      fibrosis and increased collagen proliferation in peripheral area of mesh was seen
      in Group 1 subjects, whereas a mild fibroblastic activity among mesh fibers in
      Group 3 subjects. CONCLUSIONS: FS has no negative effect on ilioinguinal nerve.
      FS application may protect the nerve from the harmful effects of polypropylene
      mesh in inguinal hernia repair.

PMID- 21951138
TI  - Effect of individual suppression of RBCS multigene family on Rubisco contents in
      rice leaves.
AB  - In higher plants, a small subunit of Rubisco is encoded for by an RBCS multigene
      family in the nuclear genome. However, it is unknown how each multigene member
      contributes to the accumulation of Rubisco holoenzyme. Here, four RBCS genes that
      are highly expressed in leaf blaedes of rice (Oryza sativa L.) were individually
      suppressed by RNAi, and the effects on leaf Rubisco content were examined at
      seedling, vegetative and reproductive stages. Rubisco contents in each transgenic
      line declined irrespective of growth stage, and the ratios of Rubisco-N to total
      N were 66-96% of wild-type levels. The mRNA levels of the suppressed RBCS genes
      declined significantly, whereas those of the unsuppressed ones did not change
      drastically. These results indicate that four RBCS genes all contribute to
      accumulation of Rubisco holoenzyme irrespective of growth stage and that
      suppression of one RBCS gene is not fully compensated by other RBCS genes.
      Additionally, the mRNA levels of the large subunit of Rubisco showed a change
      similar to that of total RBCS mRNA level irrespective of genotype and growth
      stage. These results suggest that gene expression of RBCS and RBCL is regulated
      in a coordinated manner at the transcript level in rice.

PMID- 21951139
TI  - Aortic regurgitation due to perforation of the right coronary cusp 10 years after
      implantation of a freestyle stentless bioprosthesis.
AB  - Valve deterioration following aortic valve replacement using the Freestyle
      stentless bioprosthesis is related to cusp tear, operative injury, or infection.
      We report a patient with aortic regurgitation due to perforation of the right
      coronary cusp 10 years after implantation of a Freestyle stentless bioprosthesis
      in the absence of endocarditis.

PMID- 21951140
TI  - Awareness of deficits and on-road driving performance.
AB  - This study examined the relationship of neuropsychological and on-road driving
      evaluations among adults with acquired brain injury (ABI), and the extent to
      which that relationship is moderated by awareness of deficit. Participants were
      62 pairs of adults with ABI and significant-other informants and 40 healthy
      controls (N = 102). Adults with ABI and controls completed neuropsychological and
      on-road evaluations. Multiple regression indicated that neuropsychological
      performance and the interaction between awareness of deficit and
      neuropsychological performance each explained significant variance in driving
      performance (i.e., the relationship between neuropsychological performance and on
      road outcome depends on level of awareness). The moderation effect was
      illustrated by different relationships between neuropsychological and on-road
      performances among awareness groups: Among adults with impaired awareness (n =
      21), neuropsychological functioning was substantially related to driving
      outcomes; in contrast, driving outcome showed weak relation to neuropsychological
      functioning among those with intact awareness (n = 24) or hypervigilance (n = 17)
      toward deficits. An exception was that processing speed showed modest relation to
      on-road outcome for all groups, including controls. Awareness of deficit has a
      considerable influence on driving outcomes both directly and as a moderator
      between the relationship of neuropsychological functioning and driving
      performance. When adults with ABI lack appreciation for their impairments, their
      neuropsychological status is especially important in predicting driving outcomes.

PMID- 21951150
TI  - Formation of kinetically trapped nanoscopic unilamellar vesicles from metastable
      nanodiscs.
AB  - Zwitterionic long-chain lipids (e.g., dimyristoyl phosphatidylcholine, DMPC)
      spontaneously form onion-like, thermodynamically stable structures in aqueous
      solutions (commonly known as multilamellar vesicles, or MLVs). It has also been
      reported that the addition of zwitterionic short-chain (i.e., dihexanoyl
      phosphatidylcholine, DHPC) and charged long-chain (i.e., dimyristoyl
      phosphatidylglycerol, DMPG) lipids to zwitterionic long-chain lipid solutions
      results in the formation of unilamellar vesicles (ULVs). Here, we report a
      kinetic study on lipid mixtures composed of DMPC, DHPC, and DMPG. Two membrane
      charge densities (i.e., [DMPG]/[DMPC] = 0.01 and 0.001) and two solution
      salinities (i.e., [NaCl] = 0 and 0.2 M) are investigated. Upon dilution of the
      high-concentration samples at 50  degrees C, thermodynamically stable MLVs are
      formed, in the case of both weakly charged and high salinity solution mixtures,
      implying that the electrostatic interactions between bilayers are insufficient to
      cause MLVs to unbind. Importantly, in the case of these samples small angle
      neutron scattering (SANS) data show that, initially, nanodiscs (also known as
      bicelles) or bilayered ribbons form at low temperatures (i.e., 10  degrees C),
      but transform into uniform size, nanoscopic ULVs after incubation at 10  degrees
      C for 20 h, indicating that the nanodisc is a metastable structure. The
      instability of nanodiscs may be attributed to low membrane rigidity due to a
      reduced charge density and high salinity. Moreover, the uniform-sized ULVs
      persist even after being heated to 50  degrees C, where thermodynamically stable
      MLVs are observed. This result clearly demonstrates that these ULVs are
      kinetically trapped, and that the mechanical properties (e.g., bending rigidity)
      of 10  degrees C nanodiscs favor the formation of nanoscopic ULVs over that of
      MLVs. From a practical point of view, this method of forming uniform-sized ULVs
      may lend itself to their mass production, thus making them economically feasible
      for medical applications that depend on monodisperse lipid-based systems for
      therapeutic and diagnostic purposes.

PMID- 21951151
TI  - Analysis of 256 cases of basal cell carcinoma after either one-step or two-step
      surgery in a Japanese institution.
AB  - Basal cell carcinoma (BCC) is a common skin cancer that arises from the cells of
      the basal layer of the epithelium or from the external root sheath of the hair
      follicle. In the present report, 256 cases treated surgically between 1999 and
      2008 in our department were retrospectively analyzed. The most frequent BCC
      locations included the face (77.8%), especially the nose (26.9%) and eyelids
      (21.5%). Incomplete excisions occurred in 21 cases. Two patients experienced
      local recurrence; one of these patients exhibited a bone metastasis while the
      other had a metastasis of the parotid gland without the local recurrence. The
      rate of local BCC recurrence was 0.78%, which is lower than that described in
      previous reports. We categorized BCC into four histological types: superficial,
      solid, adenoid and infiltrative. The solid type was the most frequent
      histological type (62.1%). For preventive recurrence, we treated BCC patients
      with two-step surgery when the tumor was large or histologically invasive. At the
      first step, we excised the tumor with a sufficient safety margin, and at the
      second step, we performed reconstruction after the histological confirmation that
      no remnant malignant cells were in the tumor margins. In the present report, no
      local recurrence occurred in patients following the two-step surgery. Therefore,
      two-step surgery is recommended for tumors at locations and with histological
      types related to frequent recurrence.

PMID- 21951152
TI  - Single step modified ink staining for Tzanck test: quick detection of herpetic
      giant cells in Tzanck smear.
AB  - Tzanck test has been recently re-evaluated as a method for the diagnosis of
      herpes virus infection. Giemsa staining for the Tzanck test is time-consuming and
      laborious. There is a need to develop simple and quick staining methods for
      bedside diagnosis of this disease. We report a single step and quick method for
      staining herpes giant cells in Tzanck smears using routinely available inks and
      physiological saline. A keratinocyte cell line (HaCaT) was cultured on a slide
      glass and stained with various commercially available blue, blue-black and black
      inks serially diluted with physiological saline. Clinical smear samples from
      herpes lesions were also stained with these solutions without specific
      pretreatment. The nuclei of HaCaT were clearly stained showing high contrast with
      the cytoplasm using 5% Parker-Quink blue-black ink saline solution. Concentration
      of ink solution higher or lower than 5% resulted in less contrast. Blue or black
      inks or other manufacturers' inks can also be used, but staining of the cultured
      keratinocytes was less clear. Smear of clinical samples from herpes lesions were
      also stained with 5% ink solution. The nuclei of the multinucleated giant cells
      were clearly stained, and the sample could be immediately used for microscopic
      examination. One step staining of Tzanck smear using this diluted ink solution is
      an inexpensive and a convenient bedside diagnostic tool for the dermatologist.

PMID- 21951153
TI  - Melatonin and its analogs in insomnia and depression.
AB  - Benzodiazepine sedative-hypnotic drugs are widely used for the treatment of
      insomnia. Nevertheless, their adverse effects, such as next-day hangover,
      dependence and impairment of memory, make them unsuitable for long-term
      treatment. Melatonin has been used for improving sleep in patients with insomnia
      mainly because it does not cause hangover or show any addictive potential.
      However, there is a lack of consistency on its therapeutic value (partly because
      of its short half-life and the small quantities of melatonin employed). Thus,
      attention has been focused either on the development of more potent melatonin
      analogs with prolonged effects or on the design of slow release melatonin
      preparations. The MT(1) and MT(2) melatonergic receptor ramelteon was effective
      in increasing total sleep time and sleep efficiency, as well as in reducing sleep
      latency, in insomnia patients. The melatonergic antidepressant agomelatine,
      displaying potent MT(1) and MT(2) melatonergic agonism and relatively weak
      serotonin 5HT(2C) receptor antagonism, was found effective in the treatment of
      depressed patients. However, long-term safety studies are lacking for both
      melatonin agonists, particularly considering the pharmacological activity of
      their metabolites. In view of the higher binding affinities, longest half-life
      and relative higher potencies of the different melatonin agonists, studies using
      2 or 3mg/day of melatonin are probably unsuitable to give appropriate comparison
      of the effects of the natural compound. Hence, clinical trials employing
      melatonin doses in the range of 50-100mg/day are warranted before the relative
      merits of the melatonin analogs versus melatonin can be settled.

PMID- 21951155
TI  - An analysis of the isomerization energies of 1,2-/1,3-diazacyclobutadiene,
      pyrazole/imidazole, and pyridazine/pyrimidine with the turn-upside-down approach.
AB  - The isomerization energies of 1,2- and 1,3-diazacyclobutadiene, pyrazole and
      imidazole, and pyridazine and pyrimidine are 10.6, 9.4, and 20.9 kcal/mol,
      respectively, at the BP86/TZ2P level of theory. These energies are analyzed using
      a Morokuma-like energy decomposition analysis in conjunction with what we have
      called turn-upside-down approach. Our results indicate that, in the three cases,
      the higher stability of the 1,3-isomers is not due to lower Pauli repulsions but
      because of the more favorable sigma-orbital interactions involved in the
      formation of two C-N bonds in comparison with the generation of C-C and N-N bonds
      in the 1,2-isomers.

PMID- 21951156
TI  - A new method for laboratory estimation of the transverse dispersion coefficient.

PMID- 21951157
TI  - Intramolecular excimer formation for covalently linked boron dipyrromethene dyes.
AB  - Photophysical properties have been recorded for a small series of covalently
      linked, symmetrical dimers formed around boron dipyrromethene (Bodipy) dyes.
      Within the series, a control dimer is unable to adopt a cofacial arrangement
      because of steric factors, while a second dimer possesses sufficient internal
      flexibility to form the cofacial geometry but with little overlap of the Bodipy
      units. The other three members of the series take up a cofacial arrangement with
      varying bite angles between the planes of the two Bodipy units. Fluorescence
      quantum yields and excited-state lifetimes indicate differing extents of
      electronic interaction between the two Bodipy head-groups, but only the compound
      with the smallest bite angle exhibits excimer emission in solution under ambient
      conditions. Time-resolved fluorescence studies show dual-exponential decay
      kinetics in each case, while temperature-dependent emission studies reveal
      reversible coupling between monomer and lower-energy excimer states. The latter
      is weakly fluorescent, at best, and is seen clearly only for dimers having small
      bite angles. The application of high pressure to dilute solutions of these dimers
      promotes excimer formation in certain cases and leads to loss of monomer-like
      fluorescence. Under high pressure, excimer emission is more evident, and the
      overall results can be discussed in terms of subtle structural rearrangements
      that favor excimer formation.

PMID- 21951158
TI  - Metallic few-layered VS2 ultrathin nanosheets: high two-dimensional conductivity
      for in-plane supercapacitors.
AB  - With the rapid development of portable electronics, such as e-paper and other
      flexible devices, practical power sources with ultrathin geometries become an
      important prerequisite, in which supercapacitors with in-plane configurations are
      recently emerging as a favorable and competitive candidate. As is known,
      electrode materials with two-dimensional (2D) permeable channels, high
      conductivity structural scaffolds, and high specific surface areas are the
      indispensible requirements for the development of in-plane supercapacitors with
      superior performance, while it is difficult for the presently available inorganic
      materials to make the best in all aspects. In this sense, vanadium disulfide
      (VS(2)) presents an ideal material platform due to its synergic properties of
      metallic nature and exfoliative characteristic brought by the conducting S-V-S
      layers stacked up by weak van der Waals interlayer interactions, offering great
      potential as high-performance in-plane supercapacitor electrodes. Herein, we
      developed a unique ammonia-assisted strategy to exfoliate bulk VS(2) flakes into
      ultrathin VS(2) nanosheets stacked with less than five S-V-S single layers,
      representing a brand new two-dimensional material having metallic behavior aside
      from graphene. Moreover, highly conductive VS(2) thin films were successfully
      assembled for constructing the electrodes of in-plane supercapacitors. As is
      expected, a specific capacitance of 4760 MUF/cm(2) was realized here in a 150 nm
      in-plane configuration, of which no obvious degradation was observed even after
      1000 charge/discharge cycles, offering as a new in-plane supercapacitor with high
      performance based on quasi-two-dimensional materials.

PMID- 21951159
TI  - Plasma dehydroepiandrosterone sulphate and insulin-like growth factor I levels in
      obstructive sleep apnoea syndrome.
AB  - CONTEXT: We aimed to assess whether obstructive sleep apnoea syndrome (OSAS)
      affects plasma IGF-1 and dehydroepiandrosterone sulphate (DHEA-S) levels in men,
      factors implicated in the development of age-related metabolic disorders. DESIGN:
      We conducted a cross-sectional and longitudinal clinical study. PATIENTS AND
      SETTING: We measured plasma IGF-1 and DHEA-S levels in 191 non-drug-treated
      Japanese men (34 primary snorers (PS), 88 patients with mild-to-moderate OSAS and
      69 patients severe OSAS ). RESULTS: Plasma IGF-1 and DHEA-S were negatively
      correlated with age. Plasma IGF-1 was also negatively correlated with plasma
      glucose, HOMA-IR and systolic blood pressure and apnoea parameters such as the
      apnoea-hypopnea index, minimum oxygen saturation and slow-wave sleep (SWS) time.
      Plasma DHEA-S was associated with plasma glucose, HbA1c and free fatty acid and
      was negatively correlated with SWS time. To eliminate the influence of age, PS,
      patients with mild-to-moderate OSAS and severe OSAS were divided into three
      groups by age: young (<40 years), middle-aged (40-59 years) and elderly (>= 60
      years). Patients with severe OSAS aged <40 or <60 years had lower plasma IGF-1 or
      DHEA-S levels, respectively, than did the corresponding snorers and mild-to
      moderate OSAS groups. Continuous positive airway pressure therapy for generally
      16-18 months increased plasma IGF-1 levels in patients with severe OSAS aged <40
      years (n = 18). Plasma DHEA-S levels were increased in patients with severe OSAS
      aged <60 years, whose DHEA-S level was below the mean value for that age (n =
      23/41). CONCLUSION: Severe OSAS could reduce plasma IGF-1 and DHEA-S levels in
      younger, but not elderly Japanese men, which is potentially associated with the
      development of metabolic abnormalities.

PMID- 21951161
TI  - A novel hemoglobin-based oxygen carrier, polymerized porcine hemoglobin, inhibits
      H2O2-induced cytotoxicity of endothelial cells.
AB  - Hemoglobin-based oxygen carriers (HBOCs), with their capacity for delivering
      oxygen, could potentially function as red blood cell substitutes or primary
      resuscitation solutions. However, there has been some concern regarding redox
      related safety issues of HBOCs. The present study describes a novel function of
      polymerized porcine hemoglobin (pPolyHb) in protecting a human umbilical vein
      endothelial cell line from H2O2-induced cytotoxicity. Through the examination of
      H2O2 consumption and ferrylhemoglobin formation, we found that pPolyHb exhibits
      antioxidant activity, suggesting that pPolyHb may protect cells from free radical
      induced cell damage. Additionally, we investigated the effect of pPolyHb on H2O2
      induced cell cytotoxicity, and found that pPolyHb significantly inhibits H2O2
      mediated endothelial cell damage as well as apoptosis. Thus, pPolyHb may be
      developed as a new HBOC in the future.

PMID- 21951162
TI  - A survey of policies for the monitoring of fetal growth in Australian and New
      Zealand hospitals.
AB  - BACKGROUND:   Fetal growth restriction is associated with increased perinatal
      mortality and morbidity and adverse developmental outcome. However, evidence is
      lacking on optimal approaches to antenatal screening of fetal size and growth.
      AIMS:   To determine the current policies and practices for assessment of fetal
      size and monitoring fetal growth with a view to informing future research in this
      area. METHODS:   Web-based survey of Directors of Obstetrics and Gynaecology in
      maternity hospitals with over 1000 births per annum in Australia and New Zealand
      (ANZ). The survey focussed on the existence and details of guidelines for the
      clinical assessment of fetal size and growth in low- and high-risk pregnancies,
      techniques utilised for clinical assessment of fetal size and growth and the use
      of birthweight charts. RESULTS:   Completed surveys were received from 49 (66%)
      of the 74 hospitals surveyed. Forty-four percent of hospitals have a fetal growth
      screening guideline, with abdominal palpation and symphysis fundal height (SFH)
      measurement the most common screening tools. Seventy-nine percent indicated that
      obstetric or birthweight charts were in use; 39% were unsure which chart/s were
      in use, and use differed by region. There was reasonable agreement regarding
      decision to take action following discrepancies between gestational age and SFH.
      Sixty-five percent of participants are interested in participating in a
      randomised controlled trial in this area. CONCLUSIONS:   The survey revealed that
      while there is some agreement with respect to methods used in the clinical
      assessment of fetal size and growth, there is interest in ANZ hospitals to pursue
      this area of research further.

PMID- 21951160
TI  - Maternal neglect: oxytocin, dopamine and the neurobiology of attachment.
AB  - Maternal neglect, including physical and emotional neglect, is a pervasive public
      health challenge with serious long-term effects on child health and development.
      I provide an overview of the neurobiological basis of maternal caregiving, aiming
      to better understand how to prevent and respond to maternal neglect. Drawing from
      both animal and human studies, key biological systems are identified that
      contribute to maternal caregiving behaviour, focusing on the oxytocinergic and
      dopaminergic systems. Mesocorticolimbic and nigrostriatal dopamine pathways
      contribute to the processing of infant-related sensory cues leading to a
      behavioural response. Oxytocin may activate the dopaminergic reward pathways in
      response to social cues. Human neuroimaging studies are summarised that
      demonstrate parallels between animal and human maternal caregiving responses in
      the brain. By comparing different patterns of human adult attachment, we gain a
      clearer understanding of how differences in maternal brain and endocrine
      responses may contribute to maternal neglect. For example, in insecure/dismissing
      attachment, which may be associated with emotional neglect, we see reduced
      activation of the mesocorticolimbic dopamine reward system in response to infant
      face cues, as well as decreased peripheral oxytocin response to mother-infant
      contact. We are currently testing whether the administration of intranasal
      oxytocin, as part of a randomised placebo controlled trial, may reverse some of
      these neurological differences, and potentially augment psychosocial and
      behavioural interventions for maternal neglect.

PMID- 21951163
TI  - Two mechanisms for supercontraction in Nephila spider dragline silk.
AB  - Supercontraction in dragline silk of Nephila edulis spider is shown to have two
      distinct components revealed by single fiber measurements using dynamic
      mechanical thermal analysis. The first component relies on a contraction of
      maximum 13% and seems to be associated with relaxation processed through the
      glass transition, T(g), as is induced by increasing temperature and/or humidity.
      The second component is induced by liquid water to the total contraction of 30%.
      The T(g)-induced contraction is linearly correlated with the restraining stress
      on the fiber, and the mechanical properties of the partially contracted silk have
      mechanical profiles that differ from both native and fully supercontracted
      fibers. Here we present novel supercontraction data and discuss their structural
      origins, examining the relaxation of stretched orientation in the different
      primary structure sequences.

PMID- 21951164
TI  - Cerebral subcortical small vessel disease and its relation to cognition in
      elderly subjects: a pathological study in the Oxford Project to Investigate
      Memory and Ageing (OPTIMA) cohort.
AB  - BACKGROUND: Subcortical small vessel disease (SVD) is known to contribute to
      vascular cognitive impairment and vascular dementia, but understanding about the
      extent of its influence is limited because there is a lack of consensus about how
      this pathology should be assessed. METHODS: In this study we have made use of a
      simple, novel, image-matching scoring system to assess the extent of SVD in a
      group of 70 cases from the prospectively assessed Oxford Project to Investigate
      Memory and Ageing (OPTIMA) cohort. These cases were found at autopsy to have
      cerebrovascular disease and no other pathology except Braak stage 4 or less tau
      pathology, and insufficient amyloid plaque pathology to meet Consortium to
      Establish a Registry for Alzheimer's Disease (CERAD) criteria for the diagnosis
      of Alzheimer's disease. Pathology scores for SVD were correlated with cognitive
      scores [Mini-Mental State Examination (MMSE) and cognitive section of the
      Cambridge Examination for Mental Disorders in the Elderly (CAMDEX) (CAMCOG)] at
      the last clinical assessment before death. RESULTS: The severity of SVD pathology
      was inversely related to cognitive score before death (P < 0.008 for MMSE and P <
      0.024 for CAMCOG). Thirty-one per cent and 33% of cases were rated as demented by
      MMSE or CAMCOG respectively. The degree of dementia was generally mild. Age did
      not influence severity of SVD. CONCLUSIONS: An image-based scoring system for SVD
      in a group of 70 elderly subjects enabled the severity of SVD pathology to be
      assessed with results that showed a significant correlation between SVD pathology
      severity and cognitive impairment.

PMID- 21951165
TI  - Reproductive medicine network biorepository: a road map to the future.

PMID- 21951166
TI  - Proactively establishing a biologic specimens repository for large clinical
      trials: an idea whose time has come.
AB  - Large randomized clinical trials are becoming more costly, and resources to
      support them increasingly scarce. Biologic materials, such as blood, DNA, body
      fluids, or tissue samples collected and stored as a component of these studies
      represent an invaluable resource, to answer immediate secondary hypotheses, but
      also as archived material, linked to the study data, for the use of investigators
      long into the future. The regulatory climate surrounding the storage and future
      unconstrained utilization of biologic materials is evolving quickly. It is no
      longer acceptable simply to store samples and use them in an unbridled and
      unregulated fashion. Thus, to fully utilize the tremendous potential of biologic
      samples generated from large clinical trials and their related databases,
      investigators should consider proactively creating a biologic specimen
      repository, or biorepository. A repository likely assures appropriate subject
      consent, sample provenance, secure storage, and codified procedures for sample
      and data retrieval and sharing that protect the subject's confidentiality, the
      investigator's need for accurate data, and the limited resource. Importantly, the
      biorepository specimens/samples are typically collected in addition to local and
      core specimens obtained for the parent study that provide baseline assessments
      for safety and efficacy outcomes.

PMID- 21951167
TI  - Repair of nostril stenosis using a triple flap combination: boomerang,
      nasolabial, and vestibular rotation flaps.
AB  - Tissue losses within the nose due to various reasons result in the loss of normal
      anatomy and function. The external nasal valve area is one of the most important
      functional components of the nose. The columella, lobule, nostril, and alar
      region are among the components forming the external nasal valve area.
      Deformities of the nostrils are among the most frequently observed features that
      interfere with the functional anatomy of the nose. Malformations of the nostrils
      often emerge subsequent to cleft lip repairs. Stenoses are a common type of
      pathology among nostril deformities. In cases where a stenosis has formed,
      breathing problems and developmental anomalies may occur. In the patient with
      nostril stenosis presented in this report, there was a serious alar collapse and
      contracture subsequent to a cleft lip repair. In order to repair the nostril
      stenosis, a "boomerang flap" was chosen. This boomerang flap was used in
      combination with a nasolabial flap, a vestibular rotation flap, and a conchal
      cartilage graft to achieve a satisfactory repair.

PMID- 21951168
TI  - Imaging of cellular spread on a three-dimensional scaffold by means of a novel
      cell-labeling technique for high-resolution computed tomography.
AB  - Computed tomography (CT) represents a truly three-dimensional (3D) imaging
      technique that can provide high-resolution images on the cellular level. Thus,
      one approach to detect single cells is X-ray absorption-based CT, where cells are
      labeled with a dense, opaque material providing the required contrast for CT
      imaging. Within the present work, a novel cell-labeling method has been developed
      showing the feasibility of labeling fixed cells with iron oxide (FeO) particles
      for subsequent CT imaging and quantitative morphometry. A biotin-streptavidin
      detection system was exploited to bind FeO particles to its target endothelial
      cells. The binding of the particles was predominantly close to the cell centers
      on 2D surfaces as shown by light microscopy, scanning electron microscopy, and
      CT. When cells were cultured on porous, 3D polyurethane surfaces, significantly
      more FeO particles were detected compared with surfaces without cells and FeO
      particle labeling using CT. Here, we report on the implementation and evaluation
      of a novel cell detection method based on high-resolution CT. This system has
      potential in cell tracking for 3D in vitro imaging in the future.

PMID- 21951170
TI  - Synthesis, characterization, and cytotoxic activity of novel potentially pH
      sensitive nonclassical platinum(II) complexes featuring 1,3-dihydroxyacetone
      oxime ligands.
AB  - The reaction of 1,3-dihydroxyacetone oxime with diam(m)minediaquaplatinum(II)
      under basic conditions produced zwitterionic diam(m)mine(3-hydroxy-2
      (oxidoimino)propan-1-olato-kappa(2)N,O)platinum(II) complexes featuring the N,O
      chelating ligand. Upon reaction with hydrochloric acid, it was possible to
      isolate either the singly protonated species still exhibiting the intact N,O
      chelate or the open-chain chlorido complex. All complexes were characterized in
      detail with multinuclear ((1)H, (13)C, and (195)Pt) NMR spectroscopy, ESI mass
      spectrometry, and in one case X-ray diffraction. Cytotoxicity was investigated in
      three human cancer cell lines (CH1, SW480, and A549). The obtained IC(50) values
      are in the medium or even low micromolar range, remarkable for platinum complexes
      having N(3)O or N(3)Cl coordination spheres. To study the solution behavior of
      the prepared complexes at physiologically relevant proton concentrations, time
      dependent (1)H NMR measurements were performed for the ethane-1,2-diamine
      containing series at pH values of 7.4, 6.0, and exemplarily 5.0. While the
      zwitterionic complex proved to be stable at both pH 7.4 and 6.0, the protonated
      species were deprotonated at pH 7.4, tending toward ring opening in slightly
      acidic environments, as characteristic for many solid tumors. Finally, the open
      chain form stayed intact at pH 6.0, being completely converted into its chelated
      analogue at pH 7.4. A pH-dependent evaluation of antiproliferative effects of the
      two latter complexes at pH 7.4 and pH 6.0 revealed an activation under slightly
      acidic conditions, which might be of interest for further in vivo studies.

PMID- 21951169
TI  - Identification of Bax-voltage-dependent anion channel 1 complexes in digitonin
      solubilized cerebellar granule neurons.
AB  - Mitochondrial outer membrane Bax oligomers are critical for cytochrome c release,
      but the role of resident mitochondrial proteins in this process remains unclear.
      Membrane-associated Bax has primarily been studied using 3-[(3
      cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) as the solubilizing
      agent, as it does not induce conformational artifacts, although recent evidence
      indicates it may have other artifactual effects. The objective of this study was
      to investigate digitonin as an alternative detergent to assess Bax oligomeric
      state, and possible interaction with voltage-dependent anion channel (VDAC)1 in
      cerebellar granule neurons. VDAC1 co-immunoprecipitated with Bax in digitonin
      extracts from healthy and apoptotic neurons. Two-dimensional blue native-SDS-PAGE
      revealed five Bax and VDAC1 oligomers having similar masses from 120 to 500 kDa.
      The levels of two VDAC1 oligomers in Bax 1D1 immunodepleted extracts negatively
      correlated with levels of co-precipitated VDAC1, indicating the co-precipitated
      VDAC1 was derived from these oligomers. Immunodepletion with the 6A7 antibody
      modestly reduced the levels of Bax oligomers from apoptotic but not healthy
      neurons. A sixth 170 kDa oligomer containing exclusively 6A7 Bax and no VDAC1 was
      identified after apoptosis induction. CHAPS failed to solubilize VDAC1, and
      additionally yielded no distinct oligomers. We conclude that digitonin is a
      potentially useful detergent preserving Bax-VDAC1 interactions that may be
      disrupted with CHAPS.

PMID- 21951171
TI  - A combination of intravitreal bevacizumab injection with tunable argon yellow
      laser photocoagulation as a treatment for adult-onset Coats' disease.
AB  - PURPOSE: The purpose of this study was to investigate the effectiveness of
      intravitreal bevacizumab injections combined with tunable argon yellow laser
      photocoagulation as a treatment for adult-onset Coats' disease. METHODS: We
      consecutively treated 3 patients suffering from Coats' disease diagnosed in
      adulthood with a combination of intravitreal bevacizumab injection and tunable
      argon yellow laser photocoagulation. All patients received an intravitreal
      injection of 2.5 mg bevacizumab together with various sessions of laser
      photocoagulation targeting the area of telangiectasia. The patients' best
      corrected visual acuities were recorded. Fundus photography, fluorescein
      angiography (FA), and optical coherence tomography were used to monitor vascular
      and retinal exudate changes. RESULTS: Fundus photography and FA of all 3 patients
      revealed significant regression of the vascular dilatation and the aneurysmal
      appearance of the telangiectasia areas. Optical coherence tomography also showed
      a significant subsidence of the macular edema and submacular fluid in all
      patients. A concomitant improvement in visual acuity was also noted. No treatment
      related complications were identified. CONCLUSIONS: Combining intravitreal
      bevacizumab and tunable argon yellow laser photocoagulation is an efficient
      treatment of choice for Coats' disease that has been diagnosed in adulthood.

PMID- 21951172
TI  - Left apical pedunculated thrombus with normal ventricular function mimicking an
      intracardiac tumor.
AB  - Left ventricular thrombus formation in the presence of normal ventricular
      function is a rare phenomenon, with only seven cases described in the literature.
      Their morbidity arises from the embolic sequelae that ensues. The management of
      these patients is complex, and requires the decision-making process of both the
      medical and surgical teams.

PMID- 21951173
TI  - Plastid stromules are induced by stress treatments acting through abscisic acid.
AB  - Stromules are highly dynamic stroma-filled tubules that extend from the surface
      of all plastid types in all multi-cellular plants examined to date. The stromule
      frequency (percentage of plastids with stromules) has generally been regarded as
      characteristic of the cell and tissue type. However, the present study shows that
      various stress treatments, including drought and salt stress, are able to induce
      stromule formation in the epidermal cells of tobacco hypocotyls and the root
      hairs of wheat seedlings. Application of abscisic acid (ABA) to tobacco and wheat
      seedlings induced stromule formation very effectively, and application of
      abamine, a specific inhibitor of ABA synthesis, prevented stromule induction by
      mannitol. Stromule induction by ABA was dependent on cytosolic protein synthesis,
      but not plastid protein synthesis. Stromules were more abundant in dark-grown
      seedlings than in light-grown seedlings, and the stromule frequency was increased
      by transfer of light-grown seedlings to the dark and decreased by illumination of
      dark-grown seedlings. Stromule formation was sensitive to red and far-red light,
      but not to blue light. Stromules were induced by treatment with ACC (1
      aminocyclopropane-1-carboxylic acid), the first committed ethylene precursor, and
      by treatment with methyl jasmonate, but disappeared upon treatment of seedlings
      with salicylate. These observations indicate that abiotic, and most probably
      biotic, stresses are able to induce the formation of stromules in tobacco and
      wheat seedlings.

PMID- 21951175
TI  - Cutaneous Mycobacterium massiliense infection: a sporadic case in Japan.

PMID- 21951176
TI  - The Rey 15-item memory test and Spanish-speaking older adults.
AB  - The Rey 15-Item Memory Test (Rey-15) is a standard instrument frequently employed
      to assess suspect effort/motivation in English-speaking populations. The
      objective of the current study was to examine the influence of socio-demographic
      variables on this measure and provide normative data for use with Spanish
      speakers. The performance of 130 primarily Spanish-speaking, cognitively intact,
      older adults (ages 50-69) on six Rey-15 scoring systems and six embedded measures
      of suboptimal performance was examined. Approximately 8% of the sample scored
      below the recommended cut-off of 9 on the Rey-15. The lowest recall score of 6
      was also the minimum score obtained on the recognition trial. Additionally,
      scores on the alternative Rey-15 scoring methods and the embedded measures of
      suboptimal performance were lower in comparison to the normative data presently
      utilized with English speakers, yet comparable across the examined measures.
      Basic mental status and education level were significant predictors of Rey-15
      performance; however, results indicate that these variables may share a close
      relationship with socio-demographic characteristics such as acculturation level
      and years of U.S. residency. Preliminary normative data on the Rey-15 for
      primarily Spanish-speaking older adults, stratified by education, is provided in
      conjunction with a recommendation for the use of the recognition trial when
      interpreting results.

PMID- 21951178
TI  - Enhancing sensitivity and selectivity of long-period grating sensors using
      structure-switching aptamers bound to gold-doped macroporous silica coatings.
AB  - High surface area, sol-gel derived macroporous silica films doped with gold
      nanoparticles (AuNP) are used as a platform for high-density affinity-based
      immobilization of functional structure-switching DNA aptamer molecules onto
      Michelson interferometer long-period grating (LPG) fiber sensors, allowing for
      label-free detection of small molecular weight analytes such as adenosine
      triphosphate (ATP). The high surface area afforded by the sol-gel derived
      material allowed high loading of DNA aptamers, while the inclusion of gold
      nanoparticles within the silica film provided a high refractive index (RI)
      overlay, which is required to enhance the sensitivity of the LPG sensor according
      to our numerical simulations. By using a structure-switching aptamer construct
      that could release an oligonucleotide upon binding of ATP, the effective change
      in RI was both enhanced and inverted (i.e., binding of ATP caused a net reduction
      in molecular weight and refractive index), resulting in a system that prevented
      signals originating from nonspecific binding. This is the first report on the
      coupling of aptamers to LPG fiber sensors and the first use of high RI
      AuNP/silica films as supports to immobilize biomolecules onto the LPG sensor
      surface. The dual functionality of such films to both improve binding density and
      LPG sensor cladding refractive index results in a substantial enhancement in the
      sensitivity of such sensors for small molecule detection.

PMID- 21951180
TI  - Egg donation for stem cell research: ideas of surplus and deficit in Australian
      IVF patients' and reproductive donors' accounts.
AB  - We report on a study undertaken with an Australian in vitro fertilisation (IVF)
      clinic to understand IVF patients' and reproductive donors' perceptions of oocyte
      (egg) donation for stem cell research. Such perspectives are particularly
      valuable because IVF patients form a major recruitment group for oocyte donation
      for research, and because patients and donors have direct experience of the
      medical procedures involved. Similar studies of oocyte donation have been carried
      out elsewhere in the world, but to date very little social science research has
      been published that reports on donation for research, as distinct from donation
      for reproduction. Our respondents expressed a distinct unwillingness to donate
      viable oocytes for stem cell research. In our analysis we consider a number of
      factors that explain this unwillingness. These include the labour of oocyte
      production, the inscrutability of oocytes (the lack of a test to identify degrees
      of fertility) and the extent to which the oocytes' fertility sets the parameters
      for all downstream reproductive possibilities. We draw on the science studies
      literature on affordances to make sense of the social intractability of oocytes,
      and compare them with the respondents' much greater willingness to donate frozen
      embryos for human embryonic stem cells research.

PMID- 21951181
TI  - Thermodynamic analysis of strain in heteroatom derivatives of indene.
AB  - Thermochemical properties of indene, 2,3-benzofuran, indole, and N-methylindole
      have been studied to obtain a better quantitative understanding of the energetics
      associated with these compounds containing five-membered ring units. We used
      combustion calorimetry, transpiration, and high-level first-principles
      calculations to derive gaseous enthalpies of formation of the five-membered
      heterocyclic compounds. Our new values together with selected values for the
      parent heterocyclic compounds, available from the literature were used for
      calculation of the strain enthalpies H(S) of five-membered C, N, and O-containing
      cycles. The quantitative analysis of the resulting stabilization or
      destabilization of a molecule due to interaction of the benzene ring with the
      heteroatom has been performed.

PMID- 21951179
TI  - Orexin A in rat rostral ventrolateral medulla is pressor, sympatho-excitatory,
      increases barosensitivity and attenuates the somato-sympathetic reflex.
AB  - BACKGROUND AND PURPOSE: The rostral ventrolateral medulla (RVLM) maintains
      sympathetic nerve activity (SNA), and integrates adaptive reflexes. Orexin A
      immunoreactive neurones in the lateral hypothalamus project to the RVLM.
      Microinjection of orexin A into RVLM increases blood pressure and heart rate.
      However, the expression of orexin receptors, and effects of orexin A in the RVLM
      on splanchnic SNA (sSNA), respiration and adaptive reflexes are unknown.
      EXPERIMENTAL APPROACH: The effect of orexin A on baseline cardio-respiratory
      variables as well as the somato-sympathetic, baroreceptor and chemoreceptor
      reflexes in RVLM were investigated in urethane-anaesthetized, vagotomized and
      artificially ventilated male Sprague-Dawley rats (n= 50). orexin A and its
      receptors were detected with fluorescence immunohistochemistry. KEY RESULTS:
      Tyrosine hydroxylase-immunoreactive neurones in the RVLM were frequently co
      localized with orexin 1 (OX(1) ) and orexin 2 (OX(2) ) receptors and closely
      apposed to orexin A-immunoreactive terminals. Orexin A injected into the RVLM was
      pressor and sympatho-excitatory. Peak effects were observed at 50 pmol with
      increased mean arterial pressure (42 mmHg) and SNA (45%). Responses to orexin A
      (50 pmol) were attenuated by the OX(1) receptor antagonist, SB334867, and
      reproduced by the OX(2) receptor agonist, [Ala(11) , D-Leu(15) ]orexin B. Orexin
      A attenuated the somato-sympathetic reflex but increased baroreflex sensitivity.
      Orexin A increased or reduced sympatho-excitation following hypoxia or
      hypercapnia respectively. CONCLUSIONS AND IMPLICATIONS: Although central cardio
      respiratory control mechanisms at rest do not rely on orexin, responses to
      adaptive stimuli are dramatically affected by the functional state of orexin
      receptors.

PMID- 21951192
TI  - Silica-dendrimer core-shell microspheres with encapsulated ultrasmall palladium
      nanoparticles: efficient and easily recyclable heterogeneous nanocatalysts.
AB  - We report the synthesis, characterization, and catalytic properties of novel
      monodisperse SiO(2)@Pd-PAMAM core-shell microspheres containing SiO(2)
      microsphere cores and PAMAM dendrimer-encapsulated Pd nanoparticle (Pd-PAMAM)
      shells. First, SiO(2) microspheres, which were prepared by the Stober method,
      were functionalized with vinyl groups by grafting their surfaces with
      vinyltriethoxysilane (VTS). The vinyl groups were then converted into epoxides by
      using m-chloroperoxybenzoic acid. Upon treatment with amine-terminated G4
      poly(amidoamine) (PAMAM) dendrimers, the SiO(2)-supported epoxides underwent ring
      opening and gave SiO(2)@PAMAM core-shell microspheres. Pd nanoparticles within
      the cores of the SiO(2)-supported PAMAM dendrimers were synthesized by letting
      Pd(II) ions complex with the amine groups in the cores of the dendrimers and then
      reducing them into Pd(0) with NaBH(4). This produced the SiO(2)@Pd-PAMAM core
      shell microspheres. The presence of the different functional groups on the
      materials was monitored by following the changes in FTIR spectra, elemental
      analyses, and weight losses on thermogravimetric traces. Transmission electron
      microscopy (TEM) images showed the presence of Pd nanoparticles with average size
      of 1.56 +/- 0.67 nm on the surface of the monodisperse SiO(2)@Pd-PAMAM core-shell
      microspheres. The SiO(2)@Pd-PAMAM core-shell microspheres were successfully used
      as an easily recyclable catalyst for hydrogenation of various olefins, alkynes,
      keto, and nitro groups, giving ~100% conversion and high turnover numbers (TONs)
      under 10 bar H(2) pressure, at room temperature and in times ranging from 10 min
      to 3 h. In addition, the SiO(2)@Pd-PAMAM core-shell microspheres were proven to
      be recyclable catalysts up to five times with barely any leaching of palladium
      into the reaction mixture.

PMID- 21951194
TI  - Comparison of covalent and noncovalent immobilization of Malatya apricot
      pectinesterase (Prunus armeniaca L.).
AB  - Pectinesterase isolated from Malatya apricot pulp was noncovalently and
      covalently immobilized onto bentonite and glutaraldehyde-containing amino group
      functionalized porous glass beads surface at pH 8.0 and pH 9.0, respectively. The
      effect of various parameters such as pH, temperature, activation energy, heat and
      storage stability on immobilized enzyme were investigated. The optimum
      temperature of covalently and noncovalently immobilized PE was 50 degrees C. This
      value was 60 degrees C for free PE. Although optimum pH of covalently-immobilized
      PE was 8.0, this parameter was 9.0 for free and covalently-immobilized PE. The
      noncovalently immobilized enzyme exhibited better thermostability than the free
      and covalently immobilized PE.

PMID- 21951195
TI  - Effect of surfactants on the characteristics of fluconazole niosomes for enhanced
      cutaneous delivery.
AB  - Fluconazole-loaded niosomes were prepared by the film hydration method with
      different surfactants (Span and Brij series) and characterized for various
      parameters. Results showed that niosomes composed of Span 40, Span 60, and Brij
      72 were most stable with smaller size, i.e. 0.378 +/- 0.022 MUm, 0.343 +/- 0.063
      MUm, and 0.287 +/- 0.012 MUm, respectively, along with higher entrapment
      efficiency (approx. > 41%). In vitro skin permeation and retention studies
      suggested that cutaneous accumulation was affected by surfactant property and
      vesicle size. Therefore the niosomes consisting of Span 40, Span 60, and Brij 72
      surfactant are seemingly accumulated and form localized drug depots in the skin,
      thereby releasing the contents in a sustained manner and able to greatly enhance
      cutaneous retention of the drug.

PMID- 21951196
TI  - Diastereoselective Friedel-Crafts alkylation of hydronaphthalenes.
AB  - An efficient and versatile synthesis of chiral tetralins has been developed using
      both inter- and intramolecular Friedel-Crafts alkylation as a key step. The
      readily available hydronaphthalene substrates were prepared via a highly
      enantioselective metal-catalyzed ring opening of meso-oxabicyclic alkenes
      followed by hydrogenation. A wide variety of complex tetracyclic compounds have
      been isolated with high levels of regio-, diastereo-, and enantioselectivity.

PMID- 21951197
TI  - Impact of cell phone use on men's semen parameters.
AB  - The objective of the present retrospective study was to report our experience
      concerning the effects of cell phone usage on semen parameters. We examined 2110
      men attending our infertility clinic from 1993 to October 2007. Semen analysis
      was performed in all patients. Serum free testosterone (T), follicle stimulating
      hormone (FSH), luteinising hormone (LH) and prolactin (PRL) were collected from
      all patients. The information on cell phone use of the patients was recorded and
      the subjects were divided into two groups according to their cell phone use:
      group A: cell phone use (n = 991); group B: no use (n = 1119). Significant
      difference was observed in sperm morphology between the two groups. In the
      patients of group A, 68.0% of the spermatozoa featured a pathological morphology
      compared to only 58.1% in the subjects of group B. Patients with cell phone usage
      showed significantly higher T and lower LH levels than those who did not use cell
      phone. No significant difference between the two groups was observed regarding
      FSH and PRL values. Our results showed that cell phone use negatively affects
      sperm quality in men. Further studies with a careful design are needed to
      determine the effect of cell phone use on male fertility.

PMID- 21951193
TI  - Endocrine disrupters: a review of some sources, effects, and mechanisms of
      actions on behaviour and neuroendocrine systems.
AB  - Some environmental contaminants interact with hormones and may exert adverse
      consequences as a result of their actions as endocrine disrupting chemicals
      (EDCs). Exposure in people is typically a result of contamination of the food
      chain, inhalation of contaminated house dust or occupational exposure. EDCs
      include pesticides and herbicides (such as dichlorodiphenyl trichloroethane or
      its metabolites), methoxychlor, biocides, heat stabilisers and chemical catalysts
      (such as tributyltin), plastic contaminants (e.g. bisphenol A), pharmaceuticals
      (i.e. diethylstilbestrol; 17alpha-ethinylestradiol) or dietary components (such
      as phytoestrogens). The goal of this review is to address the sources, effects
      and actions of EDCs, with an emphasis on topics discussed at the International
      Congress on Steroids and the Nervous System. EDCs may alter reproductively
      relevant or nonreproductive, sexually-dimorphic behaviours. In addition, EDCs may
      have significant effects on neurodevelopmental processes, influencing the
      morphology of sexually-dimorphic cerebral circuits. Exposure to EDCs is more
      dangerous if it occurs during specific 'critical periods' of life, such as
      intrauterine, perinatal, juvenile or puberty periods, when organisms are more
      sensitive to hormonal disruption, compared to other periods. However, exposure to
      EDCs in adulthood can also alter physiology. Several EDCs are xenoestrogens,
      which can alter serum lipid concentrations or metabolism enzymes that are
      necessary for converting cholesterol to steroid hormones. This can ultimately
      alter the production of oestradiol and/or other steroids. Finally, many EDCs may
      have actions via (or independent of) classic actions at cognate steroid
      receptors. EDCs may have effects through numerous other substrates, such as the
      aryl hydrocarbon receptor, the peroxisome proliferator-activated receptor and the
      retinoid X receptor, signal transduction pathways, calcium influx and/or
      neurotransmitter receptors. Thus, EDCs, from varied sources, may have
      organisational effects during development and/or activational effects in
      adulthood that influence sexually-dimorphic, reproductively-relevant processes or
      other functions, by mimicking, antagonising or altering steroidal actions.

PMID- 21951198
TI  - Pro-sexual effects of aqueous extracts of Massularia acuminata root in male
      Wistar rats.
AB  - Aqueous extract of Massularia acuminata root at the doses of 50, 100 and 200 mg
      kg(-1) body weight was investigated for its effect on sexual behaviour in male
      Wistar rats. Phytochemical screening revealed the presence of alkaloids,
      anthraquinones, saponins, phenolics, flavonoids and tannins in the extract. The
      increased (P < 0.05) frequencies of mount and intromission, computed male sexual
      behaviour parameters and significantly prolonged ejaculatory latency by the 50
      and 100 mg kg(-1) body weight of the extract compared favourably (P > 0.05) with
      the reference drug, sildenafil citrate (Viagra). The extract also decreased the
      mount latency. The intromission latency at all the doses of the extract compared
      favourably with the distilled water-treated animals. The concentrations of serum
      testosterone, luteinising and follicle stimulating hormones increased at all the
      doses. All these are indications of prosexual effects of the extract, mediated by
      changes in the hormonal levels, brought about possibly by alkaloids, saponins
      and/or flavonoids. Overall, the present study supported the acclaimed use of M.
      acuminata root as an aphrodisiac in Yorubic medicine of Nigeria. Therefore, the
      aqueous extract of M. acuminata roots at 50 and 100 mg kg(-1) body weight may be
      explored in the management of disorders of desire, premature ejaculation and
      erectile dysfunction in males.

PMID- 21951199
TI  - Comparison of spermatic vein histology in patients with and without varicocele.
AB  - The aim of this study was to investigate and compare histological characteristics
      of spermatic veins in patients with and without varicocele. Between February 2009
      and July 2009, spermatic veins were obtained from 13 patients with varicocele.
      Microsurgical subinguinal low ligation was performed in all patients. Spermatic
      veins of patients without varicocele were obtained from 12 patients who underwent
      radical nephrectomy. Histologically, sections of veins were stained with
      haematoxylin and eosin. Mean tunica adventitia thickness size of the spermatic
      veins was 0.35 +/- 0.08 mm and 0.22 +/- 0.1 mm respectively in patients with
      varicocele and control group (P = 0.001). Similarly, mean tunica media thickness
      size of the spermatic veins was 0.25 +/- 0.05 mm and 0.09 +/- 0.04 mm
      respectively in patients with varicocele and control group (P < 0.001). No
      significant differences were detected regarding the tunica adventitia and tunica
      media thicknesses when patients with grade 2 varicocele were compared with
      patients with grade 3 varicocele (P > 0.05). No significant differences were
      detected between the tunica adventitia and tunica media thicknesses of patients
      with varicocele and sperm parameters (P > 0.05). Our study demonstrated that
      tunica adventitia and tunica media thicknesses seem to be increased in patients
      with varicocele compared with normal subjects.

PMID- 21951200
TI  - The value of epididymal protease inhibitor in differential diagnosis between
      obstructive azoospermia and non-obstructive azoospermia.
AB  - There are no efficient and noninvasive clinical tests to distinguish between
      obstructive azoospermia (OA) and non-obstructive azoospermia (NOA). Epididymal
      protease inhibitor (Eppin) protein is secreted specifically by testes and
      epididymides in male reproductive system. It does not exist in seminal plasma of
      patients with OA in theory. The seminal plasma from 40 normal men and 46
      azoospermic patients was detected via Western blot for investigating the presence
      and characteristics of Eppin protein to distinguish between OA and NOA. The cases
      were diagnosed as NOA whether Eppin in seminal plasma was positive via Western
      blot analysis. The cases were diagnosed as OA when samples were Eppin-negative.
      Additionally, percutaneous epididymal sperm aspiration (PESA) and percutaneous
      testicular sperm aspiration (PTSA) were performed on these patients at the same
      time as the diagnostic criteria to compare with Western blot analysis. Eppin
      detection in seminal plasma showed similar effectivity with PESA/PTSA in
      differential diagnosis between OA and NOA. Compared with PESA/PTSA, Eppin
      detection is a new, efficient and noninvasive method which has good clinical
      application.

PMID- 21951201
TI  - Core lower urinary tract symptom score (CLSS) for the assessment of female lower
      urinary tract symptoms: a comparative study.
AB  - OBJECTIVE: We have recently developed the core lower urinary tract symptom score
      (CLSS) questionnaire to readily address 10 important lower urinary tract symptoms
      (LUTS). The aim of the present study was to evaluate the performance of the CLSS
      in women compared with the International Prostate Symptom Score (IPSS) and
      Overactive Bladder Symptom Score (OABSS). METHODS: Three hundred and eighteen
      treatment-naive consecutive female patients, including 48 controls, completed the
      three questionnaires. Quality of life (QOL) was determined as per the IPSS QOL
      Index. The clinical diagnoses were overactive bladder (n = 69), mixed
      incontinence (n = 42), stress incontinence (n = 17), pelvic organ prolapse (n =
      56), interstitial cystitis (n = 31), bacterial cystitis (n = 16), underactive
      bladder (n = 16), and "other" (n = 23). Simple statistics and the relationship
      between symptom scores and poor QOL (QOL Index >= 4) were examined. RESULTS: All
      symptom scores were significantly increased in symptomatic women. The CLSS
      described the symptom profiles of patients with distinct conditions. The scores
      of corresponding symptoms on the three questionnaires were significantly
      correlated (r = 0.51-0.85; all P < 0.0001). Multivariate logistic regression
      modeling proved five CLSS symptoms (daytime frequency, nocturia, urgency
      incontinence, straining, and urethral pain) as independent predictors of poor
      QOL, with hazard ratios ranging from 2.0 to 4.2. The IPSS included only two
      (urgency and straining) significant symptoms. CONCLUSIONS: The IPSS alone does
      not fully evaluate female LUTS, with a possible negative impact on QOL. Using the
      CLSS questionnaire would enable a simple and comprehensive assessment of female
      LUTS.

PMID- 21951202
TI  - Introduction to lipid biochemistry, metabolism, and signaling.

PMID- 21951203
TI  - Gestational diabetes: development of an early risk prediction tool to facilitate
      opportunities for prevention.
AB  - BACKGROUND AND AIM: In the setting of advancing maternal age, escalating obesity
      and increasing Gestational Diabetes Mellitus (GDM) rates, we aimed to develop a
      novel risk prediction tool to identify high-risk women in early pregnancy,
      specifically to facilitate targeted antenatal prevention of GDM. METHODS: In this
      retrospective, observational study, first-trimester data collected routinely by
      midwifery staff in 4276 women attending a large tertiary hospital in 2007/2008
      was analysed to examine predictive factors for GDM. GDM was diagnosed with a 28
      week oral glucose tolerance test. The data set included a derivation group
      (n=2880, from 2007 deliveries) and a validation group (n = 1396, from 2008).
      Multivariate analysis generated a scoring system. RESULTS: GDM was significantly
      correlated with a number of factors: past history of GDM, increasing maternal age
      and body mass index, Asian descent and family history of diabetes. Validation
      group clinical scores achieved a sensitivity of 61.3% and specificity of 71.4%
      for differentiating women according to their risk of developing GDM. CONCLUSIONS:
      Risk factors for GDM are easily identified at the first-trimester midwifery
      hospital booking visit. A risk prediction tool, derived from risk factors in
      early pregnancy, identifies women at high risk of GDM. This represents a novel
      approach to facilitate targeted early intervention with the potential to prevent
      development of, or ameliorate, GDM.

PMID- 21951204
TI  - Behavioural profile and maternal stress in Greek young children with Williams
      syndrome.
AB  - BACKGROUND: Williams syndrome (WS) is a genetic disorder causing intellectual
      disability. Children with WS often exhibit various kinds of maladaptive
      behaviours that affect their social functioning. In order to determine whether
      these behaviours are syndrome-specific, it would be necessary to compare children
      with WS with children with other syndromes as well as to provide data on the
      socio-emotional profile in WS from a variety of cultures. The present study
      investigated the behavioural profile and its relation to maternal stress in Greek
      young children with WS in comparison with young children with Down syndrome and
      typically developing (TD) children. METHODS: Participants were 60 mothers, 20 in
      each syndrome group and 20 in the control group. The three groups were matched
      for mental age. The behavioural profile of the participants was investigated
      through the Child Behaviour Checklist (1.5-5 years) and maternal stress through
      the Parental Stress Index. RESULTS: In accordance with studies in other cultures,
      it was found that young children with WS received significantly higher rates in
      emotional problems and anxiety/depression, compared with both children with Down
      syndrome and TD children. Moreover, mothers of children with WS reported
      significantly higher scores in the Total Stress index compared with mothers of TD
      children. However, in contrast with previous studies, only 25% of children with
      WS fell into the clinical range in the total Child Behavior Checklist score.
      CONCLUSION: The consistency of the socio-emotional characteristics of children
      with WS across cultures and developmental stages implies a strong influence of
      the genetic phenotype. However, Greek mothers avoided to characterize these
      behaviours as pathological. Implications of these findings for clinical practice
      are also discussed.

PMID- 21951205
TI  - An anti-suction control for an intra-aorta pump using blood assistant index: a
      numerical simulation.
AB  - With the extensive use of the left ventricular assist device (LVAD) as a
      treatment of heart failure, suction detection has become a key issue that
      directly affects the treatment. To detect the phenomenon of suction, a blood
      assistant index (BAI) is defined, which reflects the unloading level of the pump.
      The BAI is a ratio of the external work of LVAD and the input power of
      cardiovascular system. Using the theory of model-free adaptive control algorithm,
      an anti-suction controller, which chooses the heart rate and BAI as control
      variables, is designed. As a key feature, the proposed control algorithm adjusts
      the pump speed according to not only the blood demand of circulatory system but
      also the function of the native heart. Subsequently, the performance and
      robustness of the controller are evaluated using a numerical simulation of the
      assisted circulation and an in vitro experiment. The simulation and experimental
      results demonstrate that the BAI detects the suction occur accurately, and the
      controller can maintain the heart rate and BAI tracking the reference values with
      a response time of less than 6 s.

PMID- 21951207
TI  - Highly active ethylene polymerization and regioselective 1-hexene oligomerization
      using zirconium and titanium catalysts with tridentate [ONO] ligands.
AB  - A series of tridentate dianionic ligands [4-(t)Bu-6-R-2-(3-R'-5-(t)Bu-2
      OC(6)H(2))N=CH C(6)H(2)O](2-) (L) [R = R' = (t)Bu (L1); R = CMe(2)Ph, R' = (t)Bu
      (L2); R = adamantyl, R' = (t)Bu (L3); R = R' = CMe(2)Ph (L4); R = SiMe(2)(t)Bu,
      R' = CMe(2)Ph (L5)] were synthesized. Reactions of TiCl(4) with 1 equiv of
      ligands L1-L5 in toluene afford five-coordinate titanium complexes with general
      formula LTiCl(2) [L = L1 (1); L2 (2); L3 (3); L4 (4); L5 (5)]. The addition of
      tetrahydrofuran (THF) to titanium complex 5 readily gives THF-solvated six
      coordinate complex 6, which also was obtained by reaction of TiCl(4) with 1 equiv
      of ligand L5 in THF. Reactions of ZrCl(4) with 1 or 2 equiv of ligands L1-L5
      afford six-coordinate zirconium mono(ligand) complexes LZrCl(2)(THF) [L = L2 (7);
      L4 (8); L5 (9)], and bis(ligand) complexes L(2)Zr [L = L1 (10); L4 (11)]. The
      molecular structures of complexes 2, 8, and 11 were established by single-crystal
      X-ray diffraction studies. Upon activation with methylaluminoxane, complexes 1-9
      are active for ethylene polymerization. The activities and half-lifes of the
      catalyst systems based on zirconium complexes are more than 10(6) g of
      polyethylene (mol Zr)(-1) h(-1) and 6 h, respectively. Complex 9 is more active
      and long-lived, with a turnover frequency (TOF) of 2.6 * 10(5) (mol C(2)H(4))
      (mol Zr)(-1) h(-1), a half-life of >16 h, and a total turnover number (TON) of
      more than 10(6) (mol C(2)H(4)) (mol Zr)(-1) at 20  degrees C and 0.5 MPa
      pressure. Even at 80  degrees C, complex 9/MAO catalyst system has a long
      lifetime (t(1/2) > 2 h), as well as high activity that is comparable with that at
      20  degrees C. When activated with methylaluminoxane (MAO), complex 9 also show
      moderate catalytic activity and more than 99% 2,1-regioselectivity for 1-hexene
      oligomerization.

PMID- 21951206
TI  - Green proteorhodopsin reconstituted into nanoscale phospholipid bilayers
      (nanodiscs) as photoactive monomers.
AB  - Over 4000 putative proteorhodopsins (PRs) have been identified throughout the
      oceans and seas of the Earth. The first of these eubacterial rhodopsins was
      discovered in 2000 and has expanded the family of microbial proton pumps to all
      three domains of life. With photophysical properties similar to those of
      bacteriorhodopsin, an archaeal proton pump, PRs are also generating interest for
      their potential use in various photonic applications. We perform here the first
      reconstitution of the minimal photoactive PR structure into nanoscale
      phospholipid bilayers (nanodiscs) to better understand how protein-protein and
      protein-lipid interactions influence the photophysical properties of PR. Spectral
      (steady-state and time-resolved UV-visible spectroscopy) and physical (size
      exclusion chromatography and electron microscopy) characterization of these
      complexes confirms the preparation of a photoactive PR monomer within nanodiscs.
      Specifically, when embedded within a nanodisc, monomeric PR exhibits a titratable
      pK(a) (6.5-7.1) and photocycle lifetime (~100-200 ms) that are comparable to the
      detergent-solubilized protein. These ndPRs also produce a photoactive blue
      shifted absorbance, centered at 377 or 416 nm, that indicates that protein
      protein interactions from a PR oligomer are required for a fast photocycle.
      Moreover, we demonstrate how these model membrane systems allow modulation of the
      PR photocycle by variation of the discoidal diameter (i.e., 10 or 12 nm), bilayer
      thickness (i.e., 23 or 26.5 A), and degree of saturation of the lipid acyl chain.
      Nanodiscs also offer a highly stable environment of relevance to potential device
      applications.

PMID- 21951208
TI  - Pharmacokinetic evaluation and antitumor activity of 2-methoxyestradiol
      nanosuspension.
AB  - The aim of the present study was to evaluate the pharmacokinetic and antitumor
      activity of 2-methoxyestradiol (2-ME) nanosuspension relative to 2-ME solution
      both in vitro and in vivo. The pharmacokinetics of 2-ME administered either as a
      nanosuspension or as a solution were compared after I.V. administration to rats.
      In plasma, 2-ME nanosuspension exhibited a significantly (p < 0.01) reduced
      C(max) (1022.8 +/- 467.4 ng/mL versus 2559.2 +/- 775.8 ng/mL) and AUC(0-240min)
      (41566.8 +/- 965.5 ng/mL min versus 79557.7 +/- 256.2 ng/mL min), and a
      significantly (p < 0.01) greater volume of distribution (3.18-fold), clearance
      (1.85-fold), and elimination half-life (156.6 +/- 33.5 min versus 70.0 +/- 22.6
      min) compared to the 2-ME solution. Methyl tetrazolium (MTT) assay showed that
      nanosuspension could significantly enhance the cytotoxicity of 2-ME on EC9706
      cells in vitro. After 72 h exposure, the IC(50) value of 2-ME nanosuspension was
      much lower than that of 2-ME solution (1.81 +/- 0.15 MUmol/L versus 4.14 +/- 0.30
      MUmol/L). Studies on BALB/c mice with EC9706 solid tumors demonstrated
      significantly greater inhibition of tumor growth following treatment with 2-ME
      nanosuspension than 2-ME solution at the same dosage. These results suggest that
      the delivery of 2-ME nanosuspension is a promising approach for the treatment of
      tumors.

PMID- 21951209
TI  - TNF-alpha-induces airway hyperresponsiveness to cholinergic stimulation in guinea
      pig airways.
AB  - BACKGROUND AND PURPOSE: TNF-alpha is an inflammatory cytokine implicated in the
      pathogenesis of asthma and it causes airway inflammation, bronchoconstriction and
      airway hyperresponsiveness to a number of spasmogens following inhalation.
      EXPERIMENTAL APPROACH: We compared contractions of guinea pig isolated trachea
      incubated with saline or TNF-alpha for 1, 2 or 4 days to electrical field
      stimulation (EFS), 5-HT or methacholine. In addition, we compared
      bronchoconstriction in anaesthetized guinea pigs 6 h after intratracheal
      instillation of saline or TNF-alpha to vagal nerve stimulation, i.v. 5-HT or
      methacholine. Differential counts were performed on the bronchoalvelolar lavage
      fluid (BALF). KEY RESULTS: Maximum contractions to methacholine, 5-HT and EFS
      were not different between freshly prepared and saline-incubated tissues.
      Exposure to TNF-alpha concentration-dependently potentiated contractions to 5-HT
      and EFS, but not methacholine. All contractions were atropine-sensitive, but not
      hexamethonium-sensitive. 5-HT-evoked contractions were inhibited by ketanserin or
      epithelial denudation. Only EFS-evoked contractions were tetrodotoxin-sensitive.
      Vagal stimulation, i.v. 5-HT or MCh caused a significant atropine-sensitive,
      frequency- and dose-dependent bronchoconstriction and decreased blood pressure
      similarly in both saline and TNF-alpha pre-treated animals. TNF-alpha potentiated
      the bronchoconstriction to vagal stimulation and 5-HT, but not MCh. The BALF from
      saline-treated animals contained predominantly macrophages, whereas that from TNF
      alpha-treated animals contained neutrophils. CONCLUSIONS AND IMPLICATIONS: TNF
      alpha caused airway hyperresponsiveness to nerve stimulation in vivo and
      increased contractility in vitro. However, responsiveness to MCh was unchanged,
      suggesting a pre-synaptic action of TNF-alpha on parasympathetic nerves. TNF
      alpha-induced airway hyperresponsiveness to 5-HT suggested an increased 5-HT(2A)
      receptor-mediated acetylcholine release from epithelial cells.

PMID- 21951211
TI  - Carpentier edwards porcine valved conduit for right ventricular outflow tract
      reconstruction.
AB  - BACKGROUND: The optimal conduit for right ventricular outflow tract (RVOT)
      reconstruction is uncertain, with varying degrees of longevity reported for
      pericardial, homograft, and xenograft valves utilized in this position. METHODS:
      A retrospective review of children and adults with congenital heart disease who
      underwent RVOT reconstruction with the Carpentier EdwardsTM (CE) porcine valved
      conduit was conducted from 2001 to 2009 at the University of Rochester and SUNY
      Upstate Medical Centers. Clinical data were analyzed for each subject according
      to conduit size, and all of the Doppler derived transconduit gradients from
      postoperative echocardiograms were analyzed. RESULTS: Two hundred and eighteen
      patients received a single CE conduit for RVOT reconstruction with conduit size
      ranging from 12 to 30 mm. Perioperative mortality was 1.8% (4/218). Follow-up
      data were available for 95% of subjects with duration of follow-up ranging from 1
      to 9 years. The increase in transconduit gradient over time was inversely
      proportional to conduit size. For the entire series, freedom from reoperation was
      70.3% at 8.2 years. Patients receiving 25 and 30 mm conduits demonstrated no
      gradient development over this period of follow-up. CONCLUSIONS: In this series,
      the CE conduit showed excellent longevity at intermediate term follow-up, with
      slower progression of conduit stenosis as measured by RVOT gradient change
      compared with previous reports.

PMID- 21951210
TI  - Relationships between in vivo microdamage and the remarkable regional material
      and strain heterogeneity of cortical bone of adult deer, elk, sheep and horse
      calcanei.
AB  - Natural loading of the calcanei of deer, elk, sheep and horses produces marked
      regional differences in prevalent/predominant strain modes: compression in the
      dorsal cortex, shear in medial-lateral cortices, and tension/shear in the plantar
      cortex. This consistent non-uniform strain distribution is useful for
      investigating mechanisms that mediate the development of the remarkable regional
      material variations of these bones (e.g. collagen orientation, mineralization,
      remodeling rates and secondary osteon morphotypes, size and population density).
      Regional differences in strain-mode-specific microdamage prevalence and/or
      morphology might evoke and sustain the remodeling that produces this material
      heterogeneity in accordance with local strain characteristics. Adult calcanei
      from 11 animals of each species (deer, elk, sheep and horses) were transversely
      sectioned and examined using light and confocal microscopy. With light
      microscopy, 20 linear microcracks were identified (deer: 10; elk: six; horse:
      four; sheep: none), and with confocal microscopy substantially more microdamage
      with typically non-linear morphology was identified (deer: 45; elk: 24; horse:
      15; sheep: none). No clear regional patterns of strain-mode-specific microdamage
      were found in the three species with microdamage. In these species, the highest
      overall concentrations occurred in the plantar cortex. This might reflect
      increased susceptibility of microdamage in habitual tension/shear. Absence of
      detectable microdamage in sheep calcanei may represent the (presumably)
      relatively greater physical activity of deer, elk and horses. Absence of
      differences in microdamage prevalence/morphology between dorsal, medial and
      lateral cortices of these bones, and the general absence of spatial patterns of
      strain-mode-specific microdamage, might reflect the prior emergence of non
      uniform osteon-mediated adaptations that reduce deleterious concentrations of
      microdamage by the adult stage of bone development.

PMID- 21951212
TI  - How many names must this disease have before...?

PMID- 21951213
TI  - A morphine/heroin vaccine with new hapten design attenuates behavioral effects in
      rats.
AB  - Heroin use has seriously threatened public heath in many countries, but the
      existing therapies continue to have many limitations. Recently, immunotherapy has
      shown efficacy in some clinical studies, including vaccines against nicotine and
      cocaine, but no opioid vaccines have been introduced in clinical studies. The
      development of a novel opioid antigen designed specifically for the prevention of
      heroin addiction is necessary. A morphine-keyhole limpet hemocyanin conjugate was
      prepared and administered subcutaneously in rats. Antibody titers in plasma were
      measured using an enzyme-linked immunosorbent assay (ELISA). Competitive ELISA
      was used to assess the selectivity of the antibodies. Dopamine concentrations in
      the nucleus accumbens in rats after vaccine administration were determined by
      high-performance liquid chromatography with electrochemical detection. The
      effects of the vaccine on the heroin-primed restatement of self-administration
      and locomotor sensitization were evaluated. A novel hapten, 6-glutarylmorphine,
      was produced, and the vaccine generated a high antibody titer response. This
      vaccine displayed specificity for both morphine and heroin, but the anti-morphine
      antibodies could not recognize dissimilar therapeutic opioid compounds, such as
      buprenorphine, methadone, naloxone, naltrexone, codeine, and nalorphine. The
      morphine antibody significantly decreased morphine-induced locomotor activity in
      rats after immunization. Importantly, rats immunized with this vaccine did not
      exhibit heroin-primed reinstatement of heroin seeking when antibody levels were
      sufficiently high. The vaccine reduced dopamine levels in the nucleus accumbens
      after morphine administration, which is consistent with its behavioral effects.
      These results suggest that immunization with a novel vaccine is an effective
      means of inducing a morphine-specific antibody response that is able to attenuate
      the behavioral and psychoactive effects of heroin.

PMID- 21951214
TI  - Helminth community structure in birds of prey (Accipitriformes and Falconiformes)
      in southern Italy.
AB  - We compared helminth communities in 6 species of birds of prey from the Calabria
      region of southern Italy. In total, 31 helminth taxa, including 17 nematodes, 9
      digeneans, 3 acanthocephalans, and 2 cestodes, were found. All helminth species
      were observed in the gastrointestinal tract, except for 3 spirurid nematodes.
      Most of the parasite species were detected in at least 2 hosts, but 13 helminth
      species were found in only 1 host. At the infracommunity level, the overall
      species richness and Brillouin's index of diversity varied by host, with the
      highest values in a generalist feeder, the Eurasian buzzard (Buteo buteo), and
      the lowest in a specialist, the western honey buzzard (Pernis apivorus). Species
      richness was gender dependent only in the sparrow hawk (Accipiter nisus). The
      helminth communities were characterized by different dominant species, namely,
      Centrorhynchus spp. (Acanthocephala) in the Eurasian buzzard and common kestrel
      (Falco tinnunculus), Parastrigea intermedia (Digenea) in the marsh harrier
      (Circus aeruginosus), Physaloptera alata (Nematoda) in the sparrow hawk,
      Serratospiculum tendo (Nematoda) in the peregrine falcon (Falco peregrinus), and
      Strigea falconis (Digenea) in the western honey buzzard. Statistical analyses
      confirmed a highly significant difference of helminth infracommunity structure
      among host species. We conclude that in the Calabria region of southern Italy,
      each of the raptor species studied is distinct in terms of its helminth
      communities, and more diverse feeding habits of the host correspond with richer
      helminth communities.

PMID- 21951215
TI  - Differences in tissue expression of HBV markers in children with HBV-associated
      glomerulonephritis.
AB  - BACKGROUND/AIMS: Hepatitis B virus-associated glomerulonephritis (HBV-GN) is
      recognized as one of the major secondary nephropathies in HBV high-risk areas. To
      determine possible differences in the expression of HBV immune markers in
      tissues, we retrospectively examined HBV immune markers in the serum, renal
      tissues, and liver tissues in 132 HBV-GN children. METHODS: All 132 patients had
      biopsy-proven HBV-GN including the presence of positive HBV antigens in the
      kidney. Serum-HBV immune markers were tested by an enzyme-linked immunosorbent
      assay. Renal and liver biopsies were done in 26 patients. All renal tissues were
      examined for HBV immune markers by immunofluorescence, and liver tissues were
      examined by immunohistochemistry. RESULTS: Among the 132 patients, all showed
      varying degrees of kidney injury. Serum hepatitis B envelope antigen (HBeAg) was
      positive in 80 patients and negative in 52 patients. The positivity rate of
      Hepatitis B core antigen in renal tissue was statistically higher in serum HBeAg
      (-) than in serum HBeAg (+) patients (96.2% vs. 55.0%). Furthermore, there was no
      relationship between the presence of hepatitis B surface antigen and HBcAg in
      liver and renal tissue. CONCLUSION: HBV markers are not consistently present in
      serum, renal tissues, and liver tissues in children with HBV-GN.

PMID- 21951216
TI  - A clinical study of a laser fluorescence device for the detection of approximal
      caries in primary molars.
AB  - OBJECTIVE: To evaluate the efficacy of laser fluorescence (LF) device in
      detecting approximal caries in primary molars. METHODS: Two hundred and sixteen
      primary molars from 96 children were inspected visually to identify possible
      caries with contact approximal surfaces. Target molars and their contralateral
      molars were examined using bitewing radiographs (BR) and LF. Depending on the
      examination findings, invasive treatments were performed on molars to identify
      the presence of cavitation. RESULTS: Of 256 surfaces evaluated from 216 primary
      molars, 128 were intact, 39 had white spots, and 89 had cavities. At the white
      spot threshold, sensitivity and specificity, respectively, were 2.56% and 94.87%
      for visual inspection (VI); 64.10% and 97.43% for BR; and 56.41% and 94.87% for
      LF. At the cavity threshold, sensitivity and specificity, respectively, were
      70.79% and 95.51% for VI; 97.75% and 93.26% for BR; and 92.14% and 97.75% for LF.
      Significant differences between intact surfaces and white spots, and white spots
      and cavities were shown through LF readings. CONCLUSIONS: Both LF and BR can
      detect cavitations on approximal surfaces of primary molars. LF could be an
      alternative to radiographs in detecting approximal caries in primary molars.

PMID- 21951217
TI  - Cytotoxic T lymphocytes mediate neuronal injury in patients with X-linked
      agammaglobulinemia and progressive neurodegenerative disease.

PMID- 21951225
TI  - Role of endothelin-1 in the hyper-responsiveness to nitrovasodilators following
      acute NOS inhibition.
AB  - BACKGROUND AND PURPOSE: Acute NOS inhibition in humans and animals is associated
      with hypersensitivity to NO donors. The mechanisms underlying this phenomenon
      have not been fully elucidated. The purpose of the present study was to assess
      whether hypersensitivity to NOS-blockade is linked to endothelin-1 (ET-1)
      signalling. EXPERIMENTAL APPROACH: Sprague Dawley rats were instrumented with
      indwelling arterial and venous catheters for continuous assessments of
      haemodynamic parameters and drug delivery, respectively. Mesenteric arteries were
      isolated and tested for reactivity by wire myography. KEY RESULTS: NOS blockade
      with L-N(G)-nitroarginine methyl ester (L-NAME) caused a pronounced increase in
      arterial blood pressure (BP) (~40 mmHg). In L-NAME-treated animals, the dose of
      sodium nitroprusside (SNP) required to cause a significant reduction in arterial
      BP was lower than in vehicle-treated rats (P < 0.001), and the magnitude of the
      reduction in BP was greater. Similar results were obtained with other NO
      mimetics, but not isoprenaline; moreover, decreasing the BP back to baseline
      levels with prazosin after L-NAME treatment did not attenuate the hyper
      responsiveness to NO donors. The increased responsiveness to NO donors was
      abolished by pretreatment with the ET(A/B) receptor antagonist, PD145065, or the
      ET(A) receptor-specific antagonist ABT627. Ex vivo, L-NAME treatment potentiated
      the constriction induced by big endothelin-1 (bET-1), the precursor to active ET
      1, but had no effect on the ET-1-mediated constriction. CONCLUSIONS AND
      IMPLICATIONS: These data suggest that the increased sensitivity to NO donors is
      mediated, at least in part, by ET-1 in vivo, and the mechanism may involve the
      conversion of bET-1 to ET-1.

PMID- 21951226
TI  - Synthesis and pigmental properties of titanium phosphates with the addition of
      urea.
AB  - As a white pigment, titanium oxide is used for cosmetic application. This oxide
      is well known to have the photo catalytic activity. Therefore, a certain degree
      of sebum is decomposed by the ultraviolet radiation in the sunlight. In this
      work, titanium phosphates were prepared as a novel white pigment. Their chemical
      composition, powder properties, photo catalytic activity, moisture retention and
      smooth were studied with the addition of urea. These white pigments had little
      photo catalytic activity. The addition of urea improved the moisture retention of
      titanium phosphates. The slipping resistance of samples became small by heating,
      on the other hand, the roughness of samples became small by the addition of urea.

PMID- 21951227
TI  - Sex steroids and the control of the Kiss1 system: developmental roles and major
      regulatory actions.
AB  - Kisspeptins, encoded by the Kiss1 gene, and their canonical receptor, GPR54 (also
      termed Kiss1R), are unanimously recognised as essential regulators of puberty
      onset and gonadotrophin secretion. These key reproductive functions stem from the
      capacity of kisspeptins to stimulate gonadotrophin-releasing hormone (GnRH)
      secretion in the hypothalamus, where discrete populations of Kiss1 neurones have
      been identified. In rodents, two major groups of hypothalamic Kiss1 neurones
      exist: one present in the arcuate nucleus (ARC) and the other located in the
      anteroventral periventricular area (AVPV/RP3V). In recent years, numerous signals
      have been identified as putative modulators of the hypothalamic Kiss1 system.
      Among them, the prominent role of sex steroids as being important regulators of
      Kiss1 neurones has been documented in different species and developmental stages,
      such as early brain sex differentiation, puberty, adulthood and senescence. These
      regulatory actions are (mainly) conducted via oestrogen receptor (ER)alpha, which
      is expressed in almost all Kiss1 neurones, and likely involve both classical and
      nonclassical pathways. The regulatory effects of sex steroids are nucleus
      specific. Thus, sex steroids inhibit the expression of Kiss1/kisspeptin at the
      ARC, as a mechanism to conduct their negative-feedback actions on gonadotrophin
      secretion. By contrast, oestrogens enhance Kiss1 expression at the AVPV/RP3V in
      rodents, suggesting the involvement of this population in the positive-feedback
      actions of oestradiol to generate the preovulatory surge of gonadotrophins. In
      addition, sex steroids have been shown to act post-transcriptionally, modulating
      GnRH/gonadotrophin responsiveness to kisspeptin. Finally, sex steroids also
      regulate the expression of co-transmitters of Kiss1 neurones, such as neurokinin
      B, whose mRNA content in the ARC fluctuates in parallel to that of Kiss1 in
      response to changes in the circulating levels of sex steroids, therefore
      suggesting the contribution of this neuropeptide in the feedback control of
      gonadotrophin secretion. In sum, compelling experimental evidence obtained in
      different mammalian (and non-mammalian) species, including primates, demonstrates
      that sex steroids are essential regulators of hypothalamic Kiss1 neurones, which
      in turn operate as conduits for their effects on GnRH neurones. The physiological
      relevance of such regulatory phenomena is thoroughly discussed.

PMID- 21951228
TI  - Detoxification of methylmercury by hydrogen sulfide-producing enzyme in Mammalian
      cells.
AB  - Methylmercury (MeHg) covalently modifies cellular proteins through their SH
      groups, resulting in cytotoxicity. We report that cystathionine beta-synthase
      (CBS), which catalyzes the production of hydrogen sulfide, contributes to
      cellular protection against MeHg. Pretreatment with NaHS or overexpression of CBS
      reduced MeHg cytotoxicity, whereas transfection with CBS small interfering RNA
      enhanced MeHg toxicity in human neuroblastoma SH-SY5Y cells. Bismethylmercury
      sulfide ((MeHg)(2)S) was identified as a metabolite of MeHg in SH-SY5Y cells
      exposed to MeHg and in the livers of rats treated with MeHg. (MeHg)(2)S had
      little chemical protein modification capability and little cytotoxicity compared
      with MeHg in vitro and in vivo.

PMID- 21951229
TI  - Transcatheter heart valve with variable geometric configuration: in vitro
      evaluation.
AB  - Clinically, the current transcatheter aortic valve (TAV) technology has shown a
      propensity for paravalvular leakage; studies have correlated this flaw to
      increased calcification at the implantation site and with nonideal geometry of
      the stented valve. The present study evaluated the hydrodynamics of different
      geometric configurations, in particular the intravalvular considerations. Three
      TAV devices were made to create a representative, size 26 mm TAV. Hydrodynamics
      were assessed using a pulse duplicator. The geometries tested were composed of
      the nominal, elliptical, triangular, and undersized shapes; along with half
      constriction, a conformation in which only a portion of the stent was
      constrained. The TAVs were assessed for transvalvular pressure gradient (TVG),
      effective orifice area (EOA), and regurgitant fraction. The nominal-sized shape
      posed a larger TVG (6.2 +/- 0.3 mm Hg) than other configurations (P < 0.001)
      except the undersized valves. EOA of the nominal sized TAV (1.7 +/- 0.1 cm(2) )
      was smaller than that of the triangular and half-elliptical versions (P < 0.001).
      The half- and full-undersized geometries had EOAs smaller than the nominal type
      (P < 0.001). Nominal shape had smaller regurgitation (6.7 +/- 1.4%) than all
      configurations (P < 0.001) except for the half-undersized (4.0 +/- 0.7, P <
      0.001) with no statistically significant difference from the full-undersized (6.8
      +/- 1.3, P = 0.724). The testing of variable geometries showed significant
      differences from the nominal geometry with respect to TVG, EOA, and regurgitant
      fraction. In particular, many of these nonideal configurations demonstrated an
      increased intravalvular regurgitation.

PMID- 21951230
TI  - Incorporation dynamics of molecular guests into two-dimensional supramolecular
      host networks at the liquid-solid interface.
AB  - The objective of this work is to study both the dynamics and mechanisms of guest
      incorporation into the pores of 2D supramolecular host networks at the liquid
      solid interface. This was accomplished by adding molecular guests to
      prefabricated self-assembled porous monolayers and the simultaneous acquisition
      of scanning tunneling microscopy (STM) topographs. The incorporation of the same
      guest molecule (coronene) into two different host networks was compared, where
      the pores of the networks either featured a perfect geometric match with the
      guest (for trimesic acid host networks) or were substantially larger than the
      guest species (for benzenetribenzoic acid host networks). Even the moderate
      temporal resolution of standard STM experiments in combination with a novel
      injection system was sufficient to reveal clear differences in the incorporation
      dynamics in the two different host networks. Further experiments were aimed at
      identifying a possible solvent influence. The interpretation of the results is
      aided by molecular mechanics (MM) and molecular dynamics (MD) simulations.

PMID- 21951231
TI  - Health professionals' perceptions of cultural influences on stroke experiences
      and rehabilitation in Kuwait.
AB  - PURPOSE: The aim of this study was to investigate the perceptions of health
      professionals who treat stroke patients in Kuwait regarding cultural influences
      on the experience of stroke and rehabilitation in Kuwait. Health professionals
      interviewed were from a variety of cultural backgrounds thus providing an
      opportunity to investigate how they perceived the influence of culture on stroke
      recovery and rehabilitation in Kuwait. METHOD: Semi-structured interviews were
      carried out with 12 health professionals with current/recent stroke
      rehabilitation experience in Kuwait, followed by thematic analysis of the
      verbatim transcripts. RESULTS: The health professionals identified several
      features of the Kuwaiti culture that they believed affected the experiences of
      stroke patients. These were religious beliefs, family involvement, limited
      education and public information about stroke, prevailing negative attitudes
      toward stroke, access to finances for private treatment, social stigma and the
      public invisibility of disabled people, difficulties identifying meaningful goals
      for rehabilitation, and an acceptance of dependency linked with the widespread
      presence of maids and other paid assistants in most Kuwaiti homes. CONCLUSION: To
      offer culturally sensitive care, these issues should be taken into account during
      the rehabilitation of Kuwaiti stroke patients in their home country and
      elsewhere.

PMID- 21951232
TI  - Initiation and inhibition of dealloying of single crystalline Cu3Au (111)
      surfaces.
AB  - Dealloying is widely utilized but is a dangerous corrosion process as well. Here
      we report an atomistic picture of the initial stages of electrochemical
      dealloying of the model system Cu(3)Au (111). We illuminate the structural and
      chemical changes during the early stages of dissolution up to the critical
      potential, using a unique combination of advanced surface-analytical tools.
      Scanning tunneling microscopy images indicate an interlayer exchange of topmost
      surface atoms during initial dealloying, while scanning Auger-electron microscopy
      data clearly reveal that the surface is fully covered by a continuous Au-rich
      layer at an early stage. Initiating below this first layer a transformation from
      stacking-reversed toward substrate-oriented Au surface structures is observed
      close to the critical potential. We further use the observed structural
      transitions as a reference process to evaluate the mechanistic changes induced by
      a thiol-based model-inhibition layer applied to suppress surface diffusion. The
      initial ultrathin Au layer is stabilized with the intermediate island morphology
      completely suppressed, along an anodic shift of the breakdown potential. Thiol
      modification induces a peculiar surface microstructure in the form of microcracks
      exhibiting a nanoporous core. On the basis of the presented atomic-scale
      observations, an interlayer exchange mechanism next to pure surface diffusion
      becomes obvious which may be controlling the layer thickness and its later change
      in orientation.

PMID- 21951233
TI  - The effects of light regimes and hormones on corneal growth in vivo and in organ
      culture.
AB  - When chicks are exposed to constant light (CL) during growth, their corneas
      become flatter and lighter in weight, and their anterior segments become
      shallower than those of chicks exposed to cyclical periods of light and dark.
      These effects have been correlated with CL suppression of cyclical changes in
      melatonin levels. The question of whether light directly influences corneal
      growth (e.g. via cryptochromes in the cornea) or acts remotely via the
      suppression of the melatonin rhythm has not yet been answered. Retinoic acid
      (RA), an ubiquitous morphogen, also causes non-functional flattening during
      corneal growth, but its effect in vivo has not been correlated with light
      regimes. We wished to characterize and distinguish between hormonal and light
      effects on corneal growth. We used organ culture to study the direct effects of
      light regimes, melatonin, and RA, and compared these results with those of
      parallel in vivo experiments. In this study, eye drops containing melatonin or RA
      were applied to corneas exposed to CL in vivo or in organ culture, and effects on
      corneal mass and hydration were measured. We applied a melatonin blocker,
      luzindole, to chick corneas in normal light/dark conditions to confirm that the
      observed melatonin effects are mediated at the cell membrane. Anterior chamber
      depth and refraction in vivo were measured. We found that, during CL exposure,
      combined application of melatonin and RA eye drops increased the depth of the
      anterior segment in vivo, (P = 0.003) and interestingly, both also reduced the
      hyperopia of CL exposure after 2 weeks (P = 0.002), thus partially reversing the
      effects of CL. RA increased corneal hydration in vivo (P = 0.030) but not in
      organ culture. Melatonin had no effect on corneal hydration in vivo, but in organ
      culture, melatonin significantly decreased hydration (P < 0.001). We found no
      evidence for a direct effect of light on corneal hydration in growing chick
      corneas in culture. Melatonin is required for normal corneal growth in vivo, and
      together melatonin and RA, or RA alone, affects the regulation of water content
      within the chick cornea. Melatonin also affects corneal hydration in vitro, but
      RA does not.

PMID- 21951234
TI  - Iron(II) vacataporphyrins: a variable annulene conformation inside a regular
      porphyrin frame.
AB  - 5,10,15,20-Tetraaryl-21-vacataporphyrin (1), an annulene-porphyrin hybrid
      containing a butadiene fragment in the macrocycle perimeter, gives paramagnetic
      iron(II) complexes 2. The porphyrin 1 is devoid of one donor atom of the
      coordination core; hence, metal ion is bound in the macrocyclic cavity by only
      three pyrrolic nitrogen atoms. The coordination sphere in 2-X (where X = Cl, Br,
      I) is completed by a halide anion. The butadiene fragment flexibility and
      constraints of coordination lead to two stereoisomers with the chain oriented
      inward (2-i-X) or outward (2-o-X) of the macrocyclic center. Axial halide
      subtraction (AgBF(4) addition) leads to two new forms differing in the butadiene
      chain configuration. The (1)H NMR spectra of all complexes show characteristics
      typical for high-spin iron(II) complexes of porphyrinoids. The dependence of the
      relaxation times T(1) versus Fe(II)...H distances (estimated by MM+ models) for
      three of the isomers is in accordance with the in, out, and/or zigzag geometries.
      The 2-o-X complex is more reactive than 2-i-X and reacts at room temperature with
      dioxygen to form the iron(II) 21-oxaporphyrin complex, conserving the iron(II)
      oxidation state. After the addition of imidazole or excess of methanol to a
      mixture of 2-o-X and 2-i-X, single five-coordinate complexes with out annulene
      configuration and two axial ligands are formed.

PMID- 21951235
TI  - The Euromelanoma skin cancer prevention campaign in Europe: characteristics and
      results of 2009 and 2010.
AB  - BACKGROUND: Euromelanoma is a skin cancer education and prevention campaign that
      started in 1999 in Belgium as 'Melanoma day'. Since 2000, it is active in a large
      and growing number of European countries under the name Euromelanoma. OBJECTIVE:
      To evaluate results of Euromelanoma in 2009 and 2010 in 20 countries, describing
      characteristics of screenees, rates of clinically suspicious lesions for skin
      cancer and detection rates of melanomas. METHODS: Euromelanoma questionnaires
      were used by 20 countries providing their data in a standardized database
      (Belgium, Croatia, Cyprus, Czech Republic, FYRO Macedonia, Germany, Greece,
      Hungary, Italy, Lithuania, Luxembourg, Malta, Moldavia, Portugal, Serbia,
      Slovenia, Spain, Sweden, Switzerland and Ukraine). RESULTS: In total, 59,858
      subjects were screened in 20 countries. Most screenees were female (64%), median
      ages were 43 (female) and 46 (male) and 33% had phototype I or II. The suspicion
      rates ranged from 1.1% to 19.4% for melanoma (average 2.8%), from 0.0% to 10.7%
      for basal cell carcinoma (average 3.1%) and from 0.0% to 1.8% for squamous cell
      carcinoma (average 0.4%). The overall positive predictive value of countries
      where (estimation of) positive predictive value could be determined was 13.0%,
      melanoma detection rates varied from 0.1% to 1.9%. Dermoscopy was used in 78% of
      examinations with clinically suspected melanoma; full body skin examination was
      performed in 72% of the screenees. CONCLUSION: Although the population screened
      during Euromelanoma was relatively young, high rates of clinically suspected
      melanoma were found. The efficacy of Euromelanoma could be improved by targeting
      high-risk populations and by better use of dermoscopy and full body skin
      examination.

PMID- 21951237
TI  - Health literacy: building upon a strong foundation.

PMID- 21951236
TI  - Health literacy and the elimination of health disparities. Foreword.

PMID- 21951238
TI  - Health literacy research: looking forward. Introduction.

PMID- 21951239
TI  - Incorporating health literacy into larger operational environments.

PMID- 21951240
TI  - Health literacy measurement: a proposed research agenda.
AB  - Although the field of health literacy is experiencing tremendous growth in terms
      of producing peer-reviewed journal articles and attracting practitioners, the
      foundation of that growth is potentially unstable. Despite a steady increase in
      their number, existing measures and screeners of health literacy are not based on
      an accepted conceptual framework and fail to align with the growing body of
      theoretical and applied work. Existing measures are mainly focused on assessing
      what individuals can read and understand in clinical contexts. This leaves
      important factors untested, such as how individuals use information, and how
      health professionals and systems communicate with patients. This article outlines
      key elements of a proposed research agenda focusing on development of a new,
      comprehensive approach to measuring health literacy.

PMID- 21951241
TI  - Back to basics: why basic research is needed to create effective health literacy
      interventions.
AB  - Limited health literacy is increasingly recognized as a public health problem.
      Growing recognition of the problem--and the need for solutions--creates an
      imperative for the field of health literacy research to identify effective
      interventions. The National Action Plan to Improve Health Literacy (U.S. DHHS,
      2010) recommends increased basic research in health literacy. This paper
      elaborates on this call by explicating what is meant by basic research and
      describing several of the ways in which basic research will benefit the field of
      health literacy research and, particularly, progress toward designing successful
      interventions.

PMID- 21951242
TI  - Interventions for individuals with low health literacy: a systematic review.
AB  - The U.S. Department of Health and Human Services recently called for action on
      health literacy. An important first step is defining the current state of the
      literature about interventions designed to mitigate the effects of low health
      literacy. We performed an updated systematic review examining the effects of
      interventions that authors reported were specifically designed to mitigate the
      effects of low health literacy. We searched MEDLINE(r), The Cumulative Index to
      Nursing and Allied Health Literature (CINAHL), PsycINFO, Educational Resources
      Information Center (ERIC), and the Cochrane Library databases (2003 forward for
      health literacy; 1966 forward for numeracy). Two reviewers independently reviewed
      titles, abstracts, and full-text articles for inclusion and included studies that
      examined outcomes by health literacy level and met other pre-specified criteria.
      One reviewer abstracted article information into evidence tables; a second
      checked accuracy. Two reviewers independently rated study quality using
      predefined criteria. Among 38 included studies, we found multiple discrete design
      features that improved comprehension in one or a few studies (e.g., presenting
      essential information by itself or first, presenting information so that the
      higher number is better, adding icon arrays to numerical information, adding
      video to verbal narratives). In a few studies, we also found consistent, direct,
      fair or good-quality evidence that intensive self-management interventions
      reduced emergency department visits and hospitalizations; and intensive self- and
      disease-management interventions reduced disease severity. Evidence for the
      effects of interventions on other outcomes was either limited or mixed. Multiple
      interventions show promise for mitigating the effects of low health literacy and
      could be considered for use in clinical practice.

PMID- 21951243
TI  - Understanding the internal and external validity of health literacy
      interventions: a systematic literature review using the RE-AIM framework.
AB  - We conducted a systematic literature review, using the RE-AIM framework, with the
      goal of determining what information is available to inform research to practice
      translation of health promotion interventions developed to address health
      literacy. Thirty-one articles reflecting 25 trials published between 2000 and
      2010 met inclusion criteria. Two researchers coded each article, using a
      validated RE-AIM (reach, effectiveness/efficacy, adoption, implementation,
      maintenance) data extraction tool, and group meetings were used to gain consensus
      on discrepancies. Across all studies (14 randomized controlled trials, 11 quasi
      experimental; 24 clinic-based, 1 community-based), the mean level of reporting RE
      AIM indicators varied by dimension (reach = 69%; efficacy/ effectiveness = 58%;
      adoption = 36%; implementation = 35%; maintenance = 11%). Among participants
      enrolled in the 25 interventions, approximately 38% were identified as low health
      literate. Only eight of the studies examined health literacy status as a
      moderator of intervention effectiveness. This review suggests that the current
      research on health promotion for participants with low health literacy provides
      insufficient information to conclude whether interventions for health literacy
      can attract the target population, achieve an effect that is sustainable, or be
      generalized outside of clinical settings. Recommendations for enhancing the
      design and reporting of these trials are provided.

PMID- 21951244
TI  - "Teach to goal": theory and design principles of an intervention to improve heart
      failure self-management skills of patients with low health literacy.
AB  - Self-management is vital for achieving optimal health outcomes for patients with
      heart failure (HF). We sought to develop an intervention to improve self
      management skills and behaviors for patients with HF, especially those with low
      health literacy. Individuals with low health literacy have difficulty reading and
      understanding written information and comprehending numerical information and
      performing calculations, and they tend to have worse baseline knowledge, short
      term memory, and working memory compared with individuals with higher health
      literacy. This paper describes theoretical models that suggest methods to improve
      the design of educational curricula and programs for low literate audiences,
      including cognitive load theory and learning mastery theory. We also outline the
      practical guiding principles for designing our intervention, which includes a
      multisession educational strategy that teaches patients self-care skills until
      they reach behavioral goals ("Teach to Goal"). Our intervention strategy is being
      tested in a randomized controlled trial to determine if it is superior to a
      single-session brief educational intervention for reducing hospitalization and
      death. If this trial shows that the "Teach to Goal" approach is superior, it
      would support the value of incorporating these design principles into educational
      interventions for other diseases.

PMID- 21951245
TI  - Literacy and retention of information after a multimedia diabetes education
      program and teach-back.
AB  - Few studies have examined the effectiveness of teaching strategies to improve
      patients' recall and retention of information. As a next step in implementing a
      literacy-appropriate, multimedia diabetes education program (MDEP), the present
      study reports the results of two experiments designed to answer (a) how much
      knowledge is retained 2 weeks after viewing the MDEP, (b) does knowledge
      retention differ across literacy levels, and (c) does adding a teach-back
      protocol after the MDEP improve knowledge retention at 2-weeks' follow-up? In
      Experiment 1, adult primary care patients (n = 113) watched the MDEP and answered
      knowledge-based questions about diabetes before and after viewing the MDEP. Two
      weeks later, participants completed the knowledge assessment a third time.
      Methods and procedures for Experiment 2 (n = 58) were exactly the same, except
      that if participants answered a question incorrectly after watching the MDEP,
      they received teach-back, wherein the information was reviewed and the question
      was asked again, up to two times. Two weeks later, Experiment 2 participants
      completed the knowledge assessment again. Literacy was measured using the S
      TOFHLA. After 2 weeks, all participants, regardless of their literacy levels,
      forgot approximately half the new information they had learned from the MDEP. In
      regression models, adding a teach-back protocol did not improve knowledge
      retention among participants and literacy was not associated with knowledge
      retention at 2 weeks. Health education interventions must incorporate strategies
      that can improve retention of health information and actively engage patients in
      long-term learning.

PMID- 21951246
TI  - The development of building wellnessTM, a youth health literacy program.
AB  - Health literacy research has concentrated on adults; there has been inadequate
      research on youth health literacy and the effect it may have on health outcomes.
      Low-income, minority populations have low levels of health literacy and are at
      higher risk of illness and disease. Building WellnessTM is a youth health
      literacy curriculum targeting low-income youth from 3rd grade to 8th grade in
      order to prepare the youth to be active, educated participants in their
      healthcare. Lessons focus on asthma, obesity and overweight, accidental injury,
      and drug and alcohol use. Curriculum development was based on qualitative and
      quantitative assessment of the target population. The preliminary findings from
      the pilot project show an increase in knowledge, improved healthy behaviors, and
      enthusiasm from participants and facilitators. The development of the pilot
      project is described, with a suggestion for future development of youth health
      literacy assessment tools.

PMID- 21951247
TI  - Amplifying diffusion of health information in low-literate populations through
      adult education health literacy classes.
AB  - Over the next decade, as literacy rates are predicted to decline, the health care
      sector faces increasing challenges to effective communication with low-literate
      groups. Considering the rising costs of health care and the forthcoming changes
      in the American health care system, it is imperative to find nontraditional
      avenues through which to impart health knowledge and functional skills. This
      article draws on classroom observations and qualitative interviews with 21
      students and 3 teachers in an adult education health literacy class to explore
      the efficacy of using adult education courses to teach functional health literacy
      skills to low-literate populations. Data were analyzed using a combination of
      thematic and content analyses. Results describe the motivation of students to
      share information within the classroom and with friends and family outside the
      classroom. This article also provides several recommendations to help ensure
      accuracy of diffused information both within and outside of the classroom.
      Ultimately, this study suggests that the adult education system is in a prime
      position to impart functional health literacy skills to low-literate populations
      in the classroom. Significantly, this study demonstrates that adult education
      students themselves may be a powerful vehicle for health communication beyond the
      walls of the classroom.

PMID- 21951248
TI  - Applicability of internationally available health literacy measures in the
      Netherlands.
AB  - Health literacy measures for use in clinical-epidemiological research have all
      been developed outside Europe. In the absence of validated Dutch measures, we
      evaluated the cross-cultural applicability of the Rapid Estimate of Adult
      Literacy in Medicine (REALM), the Newest Vital Sign (NVS), the Set of Brief
      Screening Questions (SBSQ), and the measure of Functional Communicative and
      Critical Health Literacy (FCCHL). Each measure was translated into Dutch
      following standardized procedures. We assessed feasibility, internal consistency,
      and construct validity among patients with coronary artery disease (n = 201) and
      patients with diabetes type 2 (n = 88). Patients expressed most problems in
      responding to the NVS-D. They were not familiar with the type of food label and
      had difficulties calculating in portions instead of grams. The FCCHL-D items
      seemed too theoretical for many patients. Cronbach's alpha was acceptable for all
      measures. Correlation patterns between the measures were moderately coherent with
      a priori hypotheses. All translated measures were able to distinguish between
      high- and low-educated groups of patients, with the NVS-D performing best.
      Despite reasonable psychometric properties as demonstrated so far, these measures
      need to be further developed in order to increase applicability for assessing
      health literacy in clinical-epidemiological research in the Netherlands.

PMID- 21951249
TI  - Health literacy assessment using talking touchscreen technology (Health LiTT): a
      new item response theory-based measure of health literacy.
AB  - The importance of health literacy has grown considerably among researchers,
      clinicians, patients, and policymakers. Better instruments and measurement
      strategies are needed. Our objective was to develop a new health literacy
      instrument using novel health information technology and modern psychometrics. We
      designed Health LiTT as a self-administered multimedia touchscreen test based on
      item response theory (IRT) principles. We enrolled a diverse group of 619 English
      speaking, primary care patients in clinics for underserved patients. We tested
      three item types (prose, document, quantitative) that worked well together to
      reliably measure a single dimension of health literacy. The Health LiTT score
      meets psychometric standards (reliability of 0.90 or higher) for measurement of
      individual respondents in the low to middle range. Mean Health LiTT scores were
      associated with age, race/ethnicity, education, income, and prior computer use (p
      < .05). We created an IRT-calibrated item bank of 82 items. Standard setting
      needs to be performed to classify and map items onto the construct and to
      identify measurement gaps. We are incorporating Health LiTT into an existing
      online research management tool. This will enable administration of Health LiTT
      on the same touchscreen used for other patient-reported outcomes, as well as real
      time scoring and reporting of health literacy scores.

PMID- 21951250
TI  - The association of understanding of medical statistics with health information
      seeking and health provider interaction in a national sample of young adults.
AB  - Numeracy, or, "the ability to use and understand numbers in daily life" is a
      critical component of health literacy. However, little research has focused on
      numeracy in young adults (ages 18-29). We used a national sample to examine how
      health-information seeking, trust in sources, and interactions with health care
      providers differ for young adults with lower and higher numeracy. We included
      respondents ages 18 to 29 (n = 661) from the latest administration (2008) of the
      Health Information National Trends Survey (HINTS). There were no significant
      differences between those with lower and higher numeracy for most
      sociodemographic variables, nor did numeracy predict trust in health information
      sources. However, there were several differences for health-information seeking
      and health-provider interactions. Those with lower numeracy were significantly
      more likely to say their most recent search took a lot of effort (46% vs. 24%, p
      = .0008) and was frustrating (45% vs. 22%, p = .0038). Those in the lower
      numeracy group also reported more negative interactions with health providers,
      including feeling less able to rely on their provider (62% vs. 86%, p < .0001),
      and less likely to say their provider made sure they understood information (70%
      vs. 88%, p = .0001) and helped with any uncertainty (51% vs. 75%, p < .0001),
      even when adjusting for other variables. Our data suggest that limited comfort
      with numbers and statistics can influence a variety of health-related factors for
      young adults. More research is needed to understand how health literacy skills-
      including numeracy--influence health-information seeking, patient-provider
      relationships, and health outcomes, for young adults.

PMID- 21951251
TI  - Patient activation and advocacy: which literacy skills matter most?
AB  - Attention to the effect of a patient's literacy skills on health care
      interactions is relatively new. So, too, are studies of either structural or
      personal factors that inhibit or support a patient's ability to navigate health
      services and systems and to advocate for their own needs within a service
      delivery system. Contributions of the structural environment, of interpersonal
      dynamics, and of a variety of psychological and sociological factors in the
      relationship between patients and providers have long been under study. Less
      frequently examined is the advocacy role expected of patients. However, the
      complex nature of health care in the United States increasingly requires a
      proactive stance. This study examined whether four literacy skills (reading,
      numeracy, speaking, and listening) were associated with patient self-advocacy--a
      component of health literacy itself--when faced with a hypothetical barrier to
      scheduling a medical appointment. Although all literacy skills were significantly
      associated with advocacy when examined in isolation, greater speaking and
      listening skills remained significantly associated with better patient advocacy
      when all four skills were examined simultaneously. These findings suggest that
      speaking and listening skills and support for such skills may be important
      factors to consider when developing patient activation and advocacy skills.

PMID- 21951252
TI  - Associations between older adults' spoken interactive health literacy and
      selected health care and health communication outcomes.
AB  - Recent trends in the conceptualization of health literacy lead toward expansive
      notions of health literacy as social practice, rather than as a narrower
      cognitive capacity to understand health-related texts and materials. These
      expansive and complex constructions of health literacy demand tools for assessing
      individuals' propensities to actively seek information in their interactions with
      health care professionals and other health information sources. This study
      proposes a measure of this information-exchange component of health literacy and
      examines its capacity to predict outcomes and processes such as satisfaction with
      health care and comprehension of spoken health messages. Results for this sample
      ( n = 334) of low socioeconomic status older adults (mean age = 74.70 years)
      reveal that indices derived from the Measure of Interactive Health Literacy
      (MIHL) do contribute unique variance-apart from document-based health-literacy-
      on several criterion measures such as satisfaction with health care services.
      Comprehension checking improved health message listening comprehension, but for
      White participants only. These findings invite further investigations of
      interactive health literacy involving different populations, message topics, and
      elicitation methods.

PMID- 21951253
TI  - "I cried because I didn't know if I could take care of him": toward a taxonomy of
      interactive and critical health literacy as portrayed by caregivers of children
      with special health care needs.
AB  - Although the contributions of reading ability and numeracy skills in successful
      navigation of health-related systems are understood, the skills that comprise
      interactive and critical health literacy are not fully explicit. Using a
      phenomenological approach and the conceptual frame of health literacy as an
      asset, we conducted focus group interviews with 35 caregivers of children who had
      significant medical needs. Caregiver quotes were coded and categorized and then
      compared to the Revised Blooms Taxonomy. The purpose of the analysis was to
      better understand the interactive and critical health literacy skills caregivers
      use when coordinating their children's care. The findings support a dynamic
      constructivist perspective of health literacy such that caregiver skill changed
      relative to the children's health conditions. In addition, a taxonomic code of
      cognitive and communicative skills emerged from the data. This taxonomy may be
      useful in developing instrumentation to measure interactive and critical health
      literacy as well as in identifying a potential foci of interventions aimed at
      improving interactive and critical health literacy.

PMID- 21951254
TI  - The process-knowledge model of health literacy: evidence from a componential
      analysis of two commonly used measures.
AB  - We investigated the effects of domain-general processing capacity (fluid ability
      such as working memory), domain-general knowledge (crystallized ability such as
      vocabulary), and domain-specific health knowledge for two of the most commonly
      used measures of health literacy (S-TOFHLA and REALM). One hundred forty six
      community-dwelling older adults participated; 103 had been diagnosed with
      hypertension. The results showed that older adults who had higher levels of
      processing capacity or knowledge (domain-general or health) performed better on
      both of the health literacy measures. Processing capacity interacted with
      knowledge: Processing capacity had a lower level of association with health
      literacy for participants with more knowledge than for those with lower levels of
      knowledge, suggesting that knowledge may offset the effects of processing
      capacity limitations on health literacy. Furthermore, performance on the two
      health literacy measures appeared to reflect a different weighting for the three
      types of abilities. S-TOFHLA performance reflected processing capacity as well as
      general knowledge, whereas performance on the REALM depended more on general and
      health knowledge than on processing capacity. The findings support a process
      knowledge model of health literacy among older adults, and have implications for
      selecting health literacy measures in various health care contexts.

PMID- 21951255
TI  - Subjective health literacy and older adults' assessment of direct-to-consumer
      prescription drug ads.
AB  - Older adults are increasingly the intended target of direct-to-consumer (DTC)
      prescription drug ads, but limited evidence exists as to how they assess the
      educational value of DTC ads and, more importantly, whether their assessment
      depends on their level of health literacy. In-person interviews of 170 older
      adults revealed that those with low subjective health literacy evaluated the
      educational value of DTC ads significantly lower than did those with high
      subjective health literacy. The results prompt us to pay more scholarly attention
      to determining how effectively DTC ads convey useful medical information,
      particularly to those with limited health literacy.

PMID- 21951256
TI  - Misunderstanding and potential unintended misuse of acetaminophen among
      adolescents and young adults.
AB  - Acetaminophen is highly accessible yet potentially dangerous when used
      incorrectly. In attempts to address concerns about acetaminophen, the U.S. Food
      and Drug Administration (FDA) has identified gaps in evidence about unintentional
      misuse among adolescents. Therefore, our objectives were to assess adolescents'
      (1) health literacy, (2) knowledge about acetaminophen, (3) recent use of over
      the-counter (OTC) medicines, and (4) understanding of medication dosing
      (instructions for how to use the medicine, i.e., "acetaminophen skills"). We
      conducted a cross-sectional survey of adolescents and young adults (ages 16-23
      years) recruited from education settings and health care sites in Monroe County,
      New York, from 11/08-9/09. Using structured in-person interviews, we assessed
      acetaminophen knowledge and recent use of over-the-counter (OTC) medicines.
      Through role-plays of everyday health scenarios, we assessed participants'
      abilities to identify acetaminophen in OTC products and answer questions about
      instructions for acetaminophen use. We measured health literacy with the Rapid
      Estimate of Adult Literacy in Medicine (REALM) for participants >18, and the
      REALM-Teen for those <18. Confusion about acetaminophen and its use was common.
      Limited health literacy was an independent risk factor for poor knowledge,
      misunderstanding, and potential unsafe use of acetaminophen-containing medicines;
      however, most participants at all health literacy levels erred dangerously in
      "unsafe" understanding of acetaminophen use from label instructions. Individuals
      with limited health literacy could face disproportionate risk of unsafe use of
      acetaminophen because of confusion and misunderstanding of label information.
      Better labeling, public health programs, and educational efforts could facilitate
      safer use of acetaminophen.

PMID- 21951257
TI  - Health literacy explains racial disparities in diabetes medication adherence.
AB  - Although low health literacy and suboptimal medication adherence are more
      prevalent in racial/ethnic minority groups than Whites, little is known about the
      relationship between these factors in adults with diabetes, and whether health
      literacy or numeracy might explain racial/ethnic disparities in diabetes
      medication adherence. Previous work in HIV suggests health literacy mediates
      racial differences in adherence to antiretroviral treatment, but no study to date
      has explored numeracy as a mediator of the relationship between race/ethnicity
      and medication adherence. This study tested whether health literacy and/or
      numeracy were related to diabetes medication adherence, and whether either factor
      explained racial differences in adherence. Using path analytic models, we
      explored the predicted pathways between racial status, health literacy, diabetes
      related numeracy, general numeracy, and adherence to diabetes medications. After
      adjustment for covariates, African American race was associated with poor
      medication adherence (r = -0.10, p < .05). Health literacy was associated with
      adherence (r = .12, p < .02), but diabetes-related numeracy and general numeracy
      were not related to adherence. Furthermore, health literacy reduced the effect of
      race on adherence to nonsignificance, such that African American race was no
      longer directly associated with lower medication adherence (r = -0.09, p = .14).
      Diabetes medication adherence promotion interventions should address patient
      health literacy limitations.

PMID- 21951258
TI  - Low health literacy and poor health status in Asian Americans and Pacific
      Islanders in Hawai'i.
AB  - Health literacy is understudied in Asian Americans/Pacific Islanders (AA/PI). We
      used a population-based sample in Hawai'i to consider if low health literacy is
      associated with poor health outcomes in Japanese, Filipino, Native Hawaiians, and
      other AA/PI groups compared with Whites. In data weighted and adjusted for
      population undercounts and complex survey design, low health literacy varied
      significantly by group, from 23.9% among Filipinos, 20.6% in Other AA/PI, 16.0%
      in Japanese, 15.9% in Native Hawaiians, and 13.2% in Whites (chi(2) (4) = 52.22;
      p < .001). In multivariate models, low health literacy was significantly
      associated with (a) poor self-reported health in Japanese, Filipinos, Other
      AA/PI, and Whites; (b) diabetes in Hawaiians and Japanese; and (c) depression for
      Hawaiians. Low health literacy did not significantly predict overweight/obesity
      in any ethnic grouping in multivariate models. The design and relevance of health
      literacy interventions, as well as the pathways that link health literacy to
      health status, may vary by race/ethnicity, culture, and health outcomes.

PMID- 21951259
TI  - Knowledge and perceptions of health literacy among nursing professionals.
AB  - Low health literacy affects nearly half of the U.S. population. Health care
      professionals may not recognize low health literacy in their patients nor
      understand its impact on health outcomes. The purpose of this pilot study was to
      describe nurses' knowledge and perceptions of low health literacy on patients,
      their practice, and the health system. This cross-sectional, descriptive study
      used a web-based survey to assess the knowledge and perceptions of health
      literacy among nursing professionals. Registered nurses licensed by the State of
      California were randomly selected and invited to participate in the study. Data
      analysis included descriptive statistics to describe nursing professionals'
      general knowledge and perceptions. Qualitative textual analysis was done on
      participant responses to a survey question that asks participants to define
      health literacy using their own words. Results of this study revealed that
      nursing professionals' knowledge of health literacy and their understanding on
      the role health literacy plays on patient health outcomes is limited. Health
      literacy was also reported to be a low priority among providers and
      organizations. Nursing plays an important role in direct patient care and in the
      delivery of health services. Educating nurses on health literacy and improving
      patient communication and understanding can improve health outcomes.

PMID- 21951260
TI  - Health literacy and health care spending and utilization in a consumer-driven
      health plan.
AB  - We examined health literacy and health care spending and utilization by linking
      responses of three health literacy questions to 2006 claims data of enrollees new
      to consumer-driven health plans (n = 4,130). Better health literacy on all four
      health literacy measures (three item responses and their sum) was associated with
      lower total health care spending, specifically, lower emergency department and
      inpatient admission spending (p < .05). Similarly, fewer inpatient admissions and
      emergency department visits were associated with higher adequate health literacy
      scores and better self-reports of the ability to read and learn about medical
      conditions (p-value <.05). Members with lower health literacy scores appear to
      use services more appropriate for advanced health conditions, although office
      visit rates were similar across the range of health literacy scores.

PMID- 21951261
TI  - Health literacy--a strategic asset for corporate social responsibility in Europe.
AB  - The European Commission (EU) has launched the strategy "Europe 2020" aimed to
      turn the EU into a smart, sustainable and inclusive economy delivering high
      levels of employment, productivity and social cohesion. A prerequisite for the
      success of Europe 2020 is the availability of a healthy population and a healthy
      work force. An action worth highlighting is raising corporate social
      responsibility (CSR). The aim of this paper is to present how health literacy can
      become a strategic asset in CSR through the introduction of the Collaborative
      Venture on Health Literacy and the development of a business case on health
      literacy meeting targets of Europe 2020. A scope study revealed that a majority
      of companies within the network of CSR Europe already show health-related
      employee programs on their corporate websites, but only a few are focused
      specifically on advancing health literacy. The gap leaves potential opportunities
      for interventions based on research and good practices, where businesses through
      CSR can create a health-friendly environment and stimulate the workforce to
      manage their own health, seek information, and make decisions in terms of
      promoting health and well-being, thereby transforming information into knowledge
      and increased awareness among employees.

PMID- 21951263
TI  - Oxidation with a photolabile carbonyl protecting group.
AB  - A novel oxidation approach utilizing a robust photolabile carbonyl protecting
      group reagent (1) as the oxidizing reagent has been developed. Different from
      existing methods, this approach oxidizes primary alcohols to the photosensitive
      acetals (e.g., 3), providing another unique approach to the protected aldehydes.
      Thus, for the first time, oxidation and protection are achieved in one reaction.
      Secondary alcohols are oxidized to the corresponding ketones. Moreover, the
      photolabile protecting group (PPG) also oxidizes ethers and esters. The oxidation
      is presumably via hydride abstraction by the tritylium ion generated from 1 under
      acidic conditions. However, the mechanisms for primary alcohols and secondary
      alcohols are slightly different.

PMID- 21951264
TI  - Pelvic intravenous leiomyomatosis with trans-caval extension to the heart and
      pulmonary arteries.

PMID- 21951265
TI  - Supporting language and cognitive development of infants and young children
      living in children's homes in Turkey.
AB  - AIM: The purpose of the present study was to improve language and cognitive
      development of infant and young children residing in institutional settings in
      Turkey. METHOD: In Study I, there were 12 children with a mean age of 35 months
      in the intervention group and 12 children with a mean age of 36 months in the
      control group. RESULTS: When both groups' pre-test post-test general development
      t scores and cognitive and language sub-domain developmental gaps were compared,
      neither the time nor the time by group interactions were significant.
      Nevertheless, both groups' developmental gap appeared to decline. In Study II,
      children were recruited from the same institution and randomly assigned to the
      intervention and control groups. Results indicated that infants and children who
      were in the intervention group showed a decline in the language and cognitive
      development gaps, whereas the control group children's developmental gaps were
      increased. CONCLUSIONS: It can be concluded that by increasing the quality of
      care in children's homes infants' and young children's development can be
      enhanced.

PMID- 21951266
TI  - An experimental live chimeric porcine circovirus 1-2a vaccine decreases porcine
      circovirus 2b viremia when administered intramuscularly or orally in a porcine
      circovirus 2b and porcine reproductive and respiratory syndrome virus dual
      challenge model.
AB  - Commercially available inactivated vaccines against porcine circovirus type 2
      (PCV2) have been shown to be effective in reducing PCV2 viremia. Live-attenuated,
      orally administered vaccines are widely used in the swine industry for several
      pathogens because of their ease of use yet they are not currently available for
      PCV2 and efficacy. The aims of this study were to determine the efficacy of a
      live-attenuated chimeric PCV2 vaccine in a dual-challenge model using PCV2b and
      porcine reproductive and respiratory syndrome virus (PRRSV) and to compare
      intramuscular (IM) and oral (PO) routes of vaccination. Eighty-three 2-week-old
      pigs were randomized into 12 treatment groups: four vaccinated IM, four
      vaccinated PO and four non-vaccinated (control) groups. Vaccination was performed
      at 3 weeks of age using a PCV1-2a live-attenuated vaccine followed by no
      challenge, or challenge with PCV2b, PRRSV or a combination of PCV2b and PRRSV at
      7 weeks of age. IM administration of the vaccine elicited an anti-PCV2 antibody
      response between 14 and 28 days post vaccination, 21/28 of the pigs being
      seropositive prior to challenge. In contrast, the anti-PCV2 antibody response in
      PO vaccinated pigs was delayed, only 1/27 of the pigs being seropositive at
      challenge. At 21 days post challenge, PCV2 DNA loads were reduced by 80.4% in the
      IM vaccinated groups and by 29.6% in the PO vaccinated groups. PCV1-2a (vaccine)
      viremia was not identified in any of the pigs. Under the conditions of this
      study, the live attenuated PCV1-2a vaccine was safe and provided immune
      protection resulting in reduction of viremia. The IM route provided the most
      effective protection.

PMID- 21951267
TI  - Pregravid physical activity, dietary intake, and glucose intolerance during
      pregnancy.
AB  - OBJECTIVES: To ascertain prepregnancy physical activity and dietary intake from a
      sample of women in early pregnancy and estimate the effect of prepregnancy
      lifestyle behaviors on the 1-hour glucose challenge test (GCT). METHODS: We
      conducted a prospective analysis of a racially diverse urban-based sample of 152
      pregnant women in the first trimester who were participants in the Parity,
      Inflammation and Diabetes (PID) study. Dietary intake before pregnancy was
      assessed using a modified version of the Block Rapid Food Screener, and leisure
      time physical activity before pregnancy was assessed using the Baecke
      questionnaire. Test results from a nonfasting oral GCT conducted between 26 and
      28 weeks were abstracted from the medical record. Participants were classified as
      having a positive GCT if the blood glucose measurement was >=140 mg/dL and as
      negative with a blood glucose measurement <140 mg/dL. We constructed a series of
      multiple logistic regression models, adjusting for potential confounders to
      determine if prepregnancy dietary intake and leisure activity were associated
      with response to the GCT. RESULTS: Women with higher prepregnancy leisure
      activity scores were 68% less likely to have a 1-hour GCT response >=140mg/dL.
      However, there was no association between dietary intake and response to the GCT.
      CONCLUSIONS: Our data suggest that prevention of an abnormal GCT result should
      include practices to encourage women of reproductive age to engage in leisure
      physical activity in advance of planning a pregnancy.

PMID- 21951268
TI  - Case of insulin edema occurring during intensive insulin therapy after bone
      marrow transplantation.
AB  - A 50-year-old female patient, who had had a long-term history of myelodysplastic
      syndrome and type II diabetes mellitus, had developed acute myelogenous leukemia
      and received allogeneic bone marrow transplantation (BMT). She was being treated
      with tacrolimus, methotrexate and prednisolone for prophylaxis and treatment of
      graft-versus-host disease, and with intensive insulin therapy for better glycemic
      control. The patient suddenly developed marked leg edema at 27 days after
      starting intensive insulin therapy (on day 40 after BMT) without coexistence or
      exacerbation of apparent causes such as renal failure, cardiac dysfunction or leg
      thrombosis around the onset of leg edema. Interestingly, the leg edema regressed
      soon after daytime hyperglycemia and intensive insulin therapy were performed.
      Histopathological examination revealed slight dermal edema and small bullae with
      little inflammatory infiltration but no signs of autoimmune blistering diseases
      or vasculitis. These findings indicate that the present case may be considered a
      form of so-called insulin edema occurring during intensive insulin therapy after
      BMT.

PMID- 21951269
TI  - Inferior vena cava agenesis in a patient with esophagectomy for esophageal
      cancer.

PMID- 21951270
TI  - Association study of functional polymorphisms in serotonin transporter gene with
      temporal lobe epilepsy in Han Chinese population.
AB  - BACKGROUND AND PURPOSE: Serotoninergic dysfunction was reported to be involved in
      aetiology of temporal lobe epilepsy (TLE). Serotonin (5-HT) is actively cleared
      from synaptic cleft by serotonin transporter (5-HTT). We investigated the
      association between three common polymorphisms of 5-HTT gene, which may influence
      gene expression or function, and risk for TLE. METHODS: Three hundred and thirty
      four patients with TLE and four hundred and eighty-seven non-epileptic control
      subjects from Han Chinese origin were enrolled for the present study. Polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was
      used for genotyping. RESULTS: 10-repeat allele frequency of 17 bp variable number
      of tandem repeats in the second intron (5-HTTVNTR) was moderately higher in
      patients with TLE than in controls (9.1% vs. 6.1%, P=0.0187, OR=1.55, 95%CI=1.07
      2.26). CONCLUSION: Our study suggested 10-repeat allele of 5-HTTVNTR may be
      associated with TLE susceptibility.

PMID- 21951271
TI  - Success rates of a mixture of ciprofloxacin, metronidazole, and minocycline
      antibiotics used in the non-instrumentation endodontic treatment of mandibular
      primary molars with carious pulpal involvement.
AB  - OBJECTIVE: To evaluate the clinical and radiographic success rates of three mixed
      antibiotics in the non-instrumentation endodontic treatment of primary mandibular
      molars at 24-27 months postoperatively. METHODS: Eighty cariously involved lower
      primary molars from 58 children (ages 3-8 years) received a 3Mix medicament by
      non-instrumentation endodontic treatment and were then sealed with glass-ionomer
      cement and composite resin before permanent restoration with stainless steel
      crowns. The patients received a clinical and radiographic assessment every 6
      months over a 2-year follow-up period with an intra-examiner reliability of 0.83
      1.00 (kappa value). RESULTS: In 60 cases at 24- to 27-month follow-up, the
      success rates as determined by clinical and radiographic evaluation were 75% and
      36.7%, respectively; however, the overall success rate of 3Mix non
      instrumentation endodontic treatment was 36.7% with 15.8% of cases demonstrating
      a pulpal response of internal resorption. CONCLUSIONS: Non-instrumentation
      endodontic treatment using 3Mix-MP showed good clinical success but had a low
      success rate based on radiographic evaluation at 2-year follow-up. Hence, 3Mix
      antibiotic treatment cannot replace a conventional root canal treatment agent as
      a long-term therapy.

PMID- 21951272
TI  - Restoration of ion channel function in deafness-causing KCNQ4 mutants by
      synthetic channel openers.
AB  - BACKGROUND AND PURPOSE: DFNA2 is a frequent hereditary hearing disorder caused by
      loss-of-function mutations in the voltage-gated potassium channel KCNQ4 (Kv7.4).
      KCNQ4 mediates the predominant K(+) conductance, I(K,n) , of auditory outer hair
      cells (OHCs), and loss of KCNQ4 function leads to degeneration of OHCs resulting
      in progressive hearing loss. Here we explore the possible recovery of channel
      activity of mutant KCNQ4 induced by synthetic KCNQ channel openers. EXPERIMENTAL
      APPROACH: Whole cell patch clamp recordings were performed on CHO cells
      transiently expressing KCNQ4 wild-type (wt) and DFNA2-relevant mutants, and from
      acutely isolated OHCs. KEY RESULTS: Various known KCNQ channel openers robustly
      enhanced KCNQ4 currents. The strongest potentiation was observed with a
      combination of zinc pyrithione plus retigabine. A similar albeit less pronounced
      current enhancement was observed with native I(K,n) currents in rat OHCs. DFNA2
      mutations located in the channel's pore region abolished channel function and
      these mutant channels were completely unresponsive to channel openers. However,
      the function of a DFNA2 mutation located in the proximal C-terminus was restored
      by the combined application of both openers. Co-expression of wt and KCNQ4 pore
      mutants suppressed currents to barely detectable levels. In this dominant
      negative situation, channel openers essentially restored currents back to wt
      levels, most probably through strong activation of only the small fraction of
      homomeric wt channels. CONCLUSIONS AND IMPLICATIONS: Our data suggest that by
      stabilizing the KCNQ4-mediated conductance in OHCs, chemical channel openers can
      protect against OHC degeneration and progression of hearing loss in DFNA2.

PMID- 21951273
TI  - VPAC receptors: structure, molecular pharmacology and interaction with accessory
      proteins.
AB  - The vasoactive intestinal peptide (VIP) is a neuropeptide with wide distribution
      in both central and peripheral nervous systems, where it plays important
      regulatory role in many physiological processes. VIP displays a large biological
      functions including regulation of exocrine secretions, hormone release, fetal
      development, immune responses, etc. VIP appears to exert beneficial effect in
      neuro-degenerative and inflammatory diseases. The mechanism of action of VIP
      implicates two subtypes of receptors (VPAC1 and VPAC2), which are members of
      class B receptors belonging to the super-family of GPCR. This article reviews the
      current knowledge regarding the structure and molecular pharmacology of VPAC
      receptors. The structure-function relationship of VPAC1 receptor has been
      extensively studied, allowing to understand the molecular basis for receptor
      affinity, specificity, desensitization and coupling to adenylyl cyclase. Those
      studies have clearly demonstrated the crucial role of the N-terminal ectodomain
      (N-ted) of VPAC1 receptor in VIP recognition. By using different approaches
      including directed mutagenesis, photoaffinity labelling, NMR, molecular modelling
      and molecular dynamic simulation, it has been shown that the VIP molecule
      interacts with the N-ted of VPAC1 receptor, which is itself structured as a
      'Sushi' domain. VPAC1 receptor also interacts with a few accessory proteins that
      play a role in cell signalling of receptors. Recent advances in the structural
      characterization of VPAC receptor and more generally of class B GPCRs will lead
      to the design of new molecules, which could have considerable interest for the
      treatment of inflammatory and neuro-degenerative diseases.

PMID- 21951274
TI  - Oxidative stress-dependent cyclooxygenase-2-derived prostaglandin f(2alpha)
      impairs endothelial function in renovascular hypertensive rats.
AB  - Abstract   Aims: The role of endothelium-derived contracting factors (EDCFs) in
      regulating renovascular function is yet to be elucidated in renovascular
      hypertension (RH). The current study investigated whether oxidative stress
      dependent cyclooxygenase (COX)-2-derived prostaglandin F(2alpha) (PGF(2alpha))
      impairs endothelial function in renal arteries of renovascular hypertensive rats
      (RHR). RESULTS: Renal hypertension was induced in rats by renal artery stenosis
      of both kidneys using the 2-kidney 2-clip model. Acute treatment with reactive
      oxygen species (ROS) scavengers, COX-2 inhibitors, and thromboxane-prostanoid
      receptor antagonists, but not COX-1 inhibitors, improved endothelium-dependent
      relaxations and eliminated endothelium-dependent contractions in RHR renal
      arteries. Five weeks of treatment with celecoxib or tempol reduced blood
      pressure, increased renal blood flow, and restored endothelial function in RHRs.
      Increased ROS production in RHR arteries was inhibited by ROS scavengers, but
      unaffected by COX-2 inhibitors; whereas increased PGF(2alpha) release was reduced
      by both ROS scavengers and COX-2 inhibitors. ROS also induced COX-2-dependent
      contraction in RHR renal arteries, which was accompanied by the release of COX-2
      derived PGF(2alpha). Further, chronic tempol treatment reduced COX-2 and BMP4
      upregulation, p38MAPK phosphorylation, and the nitrotyrosine level in RHR renal
      arteries. CONCLUSION: These findings demonstrate the functional importance of
      oxidative stress, which serves as an initiator of increased COX-2 activity, and
      that COX-2-derived PGF(2alpha) plays an important role in mediating endothelial
      dysfunction in RH. INNOVATION: The current study, thus, suggests that drugs
      targeting oxidative stress-dependent COX-2-derived PGF(2alpha) may be useful in
      the prevention and management of RH. Antioxid. Redox Signal. 16, 363-373.

PMID- 21951275
TI  - Ovarian cysts in MRL / MpJ mice are derived from the extraovarian rete: a
      developmental study.
AB  - MRL/MpJ (MRL) mice, commonly used as a model for autoimmune disease, have a high
      frequency of ovarian cysts originating from the rete ovarii. In the present
      study, to clarify how the rete ovarii, which are remnants of mesonephric tubules
      during embryogenesis, progress to cystic formation with aging, the morphology of
      MRL rete ovarii was analyzed and compared with that of normal C57BL/6N (B6) mice.
      In B6 mice, the rete ovarii consisted of a series of tubules, including the
      extraovarian rete (ER), the connecting rete (CR), and the intraovarian rete (IR),
      based on their location. Whereas the ER of B6 mice was composed of highly
      convoluted tubules lined by both ciliated and non-ciliated epithelia, the tubules
      in the CR and IR had only non-ciliated cells. In MRL mice, dilations of the rete
      ovarii initiated from the IR rather than the ER or CR. Although the histological
      types of cells lining the lumen of the rete ovarii were the same as those in B6
      mice, the ER in MRL mice showed a variety in morphology. In particular, the
      connections between the ER and ovary tended to disappear with increasing age and
      the development of ovarian cysts. Furthermore, the epithelium lining the large
      ovarian cysts in MRL mice had ciliated cells forming the cluster. On the basis of
      these findings, it is suggested that cystic changes of the rete ovarii in MRL
      mice are caused by the dilations of the IR with invasion of the ER and CR into
      the ovarian medulla. These data provide new pathological mechanisms for ovarian
      cyst formation.

PMID- 21951276
TI  - Progress in stem cell biology in regenerative medicine for liver disease.
AB  - Regenerative medicine using stem cells has attracted much attention, since stem
      cells are responsible for highly proliferative activity and multipotential
      ability of differentiation. Induced pluripotent stem cells and embryonic stem
      cells or the adult stem cells such as bone marrow-derived stem cells and adipose
      tissue-derived stem cells have been expected as a cell source of regenerative
      medicine. Since differentiating methods of human stem cells into the defined
      lineage of cells remains to be developed, we focus on the differentiating
      strategies of pluripotent stem cells and mesenchymal stem cells into liver
      lineage, especially on cytokine function and gene expression during hepatic
      differentiation. The survey of previously published papers discloses that the
      protocols that mimic the liver developmental process seem to be effective in
      obtaining functional hepatocytes. However, in order to develop hepatic
      regenerative medicine that is useful in a clinical setting, more effective and
      potent strategies that obtain mature hepatocytes are required.

PMID- 21951277
TI  - Synthesis and structural characterization of tris(2-mercapto-1
      adamantylimidazolyl)hydroborato complexes: a sterically demanding tripodal [S3]
      donor ligand.
AB  - The tris(2-mercapto-1-adamantylimidazolyl)hydroborato ligand, [Tm(Ad)], has been
      synthesized via the reaction of 1-adamantyl-2-mercaptoimidazole with MBH(4) (M =
      Li, K). [Tm(Ad)]M has been used to synthesize a variety of compounds of the main
      group and transition elements, including [Tm(Ad)]ZnI, {[Tm(Ad)]GaI}[GaI(4)],
      {[Tm(Ad)]GaCl}[GaCl(4)], {[Tm(Ad)]GaGa[Tm(Ad)]}[GaCl(4)](2),
      {[Tm(Ad)](2)In}[InI(4)], [Tm(Ad)]In(kappa(2)-mim(Ad))Cl, [Tm(Ad)]Ga
      >B(C(6)F(5))(3), [Tm(Ad)]In->B(C(6)F(5))(3), and [Tm(Ad)]Re(CO)(3). Structural
      characterization of [Tm(Ad)]Re(CO)(3) demonstrates that the [Tm(Ad)] ligand is
      more encapsulating than other [Tm(R)] ligands, including [Tm(Bu(t))], while IR
      spectroscopic studies indicate that the [Tm(Ad)] and [Tm(Bu(t))] ligands have
      very similar electron-donating properties.

PMID- 21951279
TI  - Role of presenilin 1 in structural plasticity of cortical dendritic spines in
      vivo.
AB  - Mutations in presenilins are the major cause of familial Alzheimer's disease
      (FAD), leading to impairments of memory and synaptic plasticity followed by age
      dependent neurodegeneration. Presenilins are the catalytic subunits of gamma
      secretase, which itself is critically involved in the processing of amyloid
      precursor protein to release neurotoxic amyloid beta (Abeta). Besides Abeta
      generation, there is growing evidence that presenilins play an essential role in
      the formation and maintenance of synapses. To further elucidate the effect of
      presenilin1 (PS1) on synapses, we performed longitudinal in vivo two-photon
      imaging of dendritic spines in the somatosensory cortex of transgenic mice over
      expressing either human wild-type PS1 or the FAD-mutated variant A246E (FAD-PS1).
      Interestingly, the consequences of transgene expression were different in two
      subtypes of cortical dendrites. On apical layer 5 dendrites, we found an enhanced
      spine density in both mice over-expressing human wild-type presenilin1 and FAD
      PS1, whereas on basal layer 3 dendrites only over-expression of FAD-PS1 increased
      the spine density. Time-lapse imaging revealed no differences in kinetically
      distinct classes of dendritic spines nor was the shape of spines affected.
      Although gamma-secretase-dependent processing of synapse-relevant proteins seemed
      to be unaltered, higher expression levels of ryanodine receptors suggest a
      modified Ca(2+) homeostasis in PS1 over-expressing mice. However, the conditional
      depletion of PS1 in single cortical neurons had no observable impact on dendritic
      spines. In consequence, our results favor the view that PS1 influences dendritic
      spine plasticity in a gain-of-function but gamma-secretase-independent manner.

PMID- 21951278
TI  - Effect of orofacial exercises on oral aperture in adults with systemic sclerosis.
AB  - PURPOSE: To examine the effect of a home orofacial exercise program on increasing
      oral aperture among adults with systemic sclerosis (SSc). METHOD: Forty-eight
      adults with SSc were assigned randomly to the multifaceted oral-health
      intervention or usual dental care control group. Participants with an oral
      aperture of <40 mm in the intervention group received an orofacial exercise
      program, which included daily manual mouth-stretching and oral-augmentation
      exercises twice a day with a total of 6 minutes for 6 months. The outcome measure
      was oral aperture which was measured at baseline, 3-months, and 6-months
      intervals. RESULTS: A significantly larger increase in oral aperture for
      participants received the orofacial exercise program was found when compared to
      those in the usual care at 3 months (P = 0.01), but not at 6-months evaluation.
      Participants' adherence rate to the exercise program was low (48.9%).
      CONCLUSIONS: The orofacial exercise program intervention for adults with SSc and
      microstomia did not show significant improvement at 6 months. In addition to the
      low exercise adherence rate, insufficient frequencies, repetitions, and durations
      of the orofacial exercises may contribute to these results.

PMID- 21951280
TI  - Emergency medicine research: to infinity and beyond!

PMID- 21951281
TI  - Superluminescent variants of marine luciferases for bioassays.
AB  - In this study, a rational synthesis of superluminescent variants from marine
      luciferases with prolonged bioluminescence has been demonstrated. A putative
      active site of a model marine luciferase, Gaussia princeps Luciferase (GLuc), was
      assigned and modified by a site-directed mutagenesis. The potent variants were
      found to generate up to 10 times stronger bioluminescence, emitting red shifts of
      up to 33 nm with natural coelenterazine than native GLuc, rendering an efficient
      optical signature in bioassays. The advantageous properties were demonstrated
      with mammalian two-hybrid assays, single-chain probes, and metastases of murine
      B16 melanoma in BALB/c nude mice. The unique ideas for engineering GLuc are
      proved to be valid even for other marine luciferases.

PMID- 21951282
TI  - Monitoring the fidelity of mitotic chromosome segregation by the spindle assembly
      checkpoint.
AB  - Accurate chromosome segregation relies on activity of the spindle assembly
      checkpoint, a surveillance mechanism that prevents premature anaphase onset until
      all chromosomes are properly attached to the mitotic spindle apparatus and
      aligned at the metaphase plate. Defects in this mechanism contribute to
      chromosome instability and aneuploidy, a hallmark of malignant cells. Here, we
      review the molecular mechanisms of activation and silencing of the spindle
      assembly checkpoint and its relationship to tumourigenesis.

PMID- 21951283
TI  - 3-O-methylfunicone, from Penicillium pinophilum, is a selective inhibitor of
      breast cancer stem cells.
AB  - OBJECTIVES: Cancer stem cells make up a subpopulation of cells within tumours
      that drive tumour initiation, growth and recurrence. They are resistant to many
      current types of cancer treatment, causing failure of such therapeutic
      approaches, including chemotherapy and radiotherapy. In the study described here,
      anti-proliferative effects of 3-O-methylfunicone (OMF), a metabolite from
      Penicillium pinophilum, were investigated on human breast cancer MCF-7 cells and
      cancer stem cells selected as mammospheres derived from MCF-7s. MATERIALS AND
      METHODS: Stemness markers were analysed on isolated mammospheres showing positive
      expression of CD24, CD29, CD44, CD133, CD184 and CD338. Cell proliferation and
      apoptosis were analysed by flow cytometry and RT-PCR. Cell colony formation
      assays were performed to evaluate colony formation of mammospheres. RESULTS AND
      CONCLUSION: OMF treatment affected both MCF-7 and mammosphere growth, inducing
      apoptosis. In addition, OMF strongly reduced stemness markers and survivin, hTERT
      and Nanog-1 gene expression. Growth of colonies in soft-agar was significantly
      affected by OMF treatment, too. Lastly, we tested ability of MCF-7 cells to form
      mammospheres after treatment with OMF or cisplatin, demonstrating that OMF
      treatment resulted in drastic reduction in number of mammospheres. These results
      introduce OMF as an effective molecule in suppressing breast cancer stem cells.

PMID- 21951284
TI  - Spontaneous and induced osteoclastogenic behaviour of human peripheral blood
      mononuclear cells and their CD14(+) and CD14(-) cell fractions.
AB  - OBJECTIVES: Osteoclasts are descended from the CD14(+) monocyte/macrophage
      lineage, but influence of other haematopoietic cells on osteoclastic commitment
      of their precursors has remained poorly understood. In this study,
      osteoclastogenic behaviour of peripheral blood mononuclear cells (PBMC) and their
      CD14(+) and CD14(-) subpopulations has been accessed, in the absence or presence
      of M-CSF and RANKL. MATERIALS AND METHODS: Cell cultures were characterized for
      presence of actin rings and vitronectin and calcitonin receptors, TRAP activity
      and calcium phosphate resorbing activity, expression of osteoclast-related genes
      and secretion of M-CSF and RANKL. RESULTS: In the absence of growth factors, PBMC
      and CD14(+) cultures had some degree of cell survival, and some spontaneous
      osteoclastogenesis was observed, only on cultures of the former. Supplementation
      with M-CSF and RANKL significantly increased osteoclastogenic behaviour of cell
      cultures, particularly CD14(+) cell cultures. Nevertheless, PBMC derived a higher
      degree of osteoclastogenesis, either as absolute values or after normalization by
      protein content. It was observed that unlike CD14(+) cells, PBMC were able to
      express M-CSF and RANKL, which increased following growth factor treatment. Also,
      expression of TNF-alpha, GM-CSF, IL-1beta, IL-6 and IL-17 was higher in PBMC
      cultures. Finally, CD14(-) cultures exhibited limited cell survival and did not
      reveal any osteoclast features. CONCLUSIONS: Results show that although
      osteoclastic precursors reside in the CD14(+) cell subpopulation, other
      populations (such as CD14(-) cells) derived from PBMC, have the ability to
      modulate osteoclastogenesis positively.

PMID- 21951285
TI  - Dose-specific effects of tumor necrosis factor alpha on osteogenic
      differentiation of mesenchymal stem cells.
AB  - OBJECTIVES: To investigate tumor necrosis factor alpha (TNF-alpha)-induced
      changes in osteogenic differentiation from mesenchymal stem cells (MSCs).
      MATERIALS AND METHODS: Blockade of nuclear factor-kappaB (NF-kappaB) was achieved
      in ST2 murine MSCs via overexpression of the NF-kappaB inhibitor, IkappaBalpha.
      Osteogenic differentiation was induced in IkappaBalpha-overexpressing ST2 cells
      and normal ST2 cells when these cells were treated with TNF-alpha at various
      concentrations. Expression levels of bone marker genes were determined using real
      time RT-PCR and ALP activity assay. In vitro mineralization was performed to
      determine long-term exposure to TNF-alpha on mineral nodule formation. MTT assay
      was used to determine the changes in cell proliferation/survival. RESULTS: Levels
      of Runx2, Osx, OC and ALP were up-regulated in cell cultures treated with TNF
      alpha at lower concentrations, while down-regulated in cell cultures treated with
      TNF-alpha at higher concentrations. Blockade of NF-kappaB signaling reversed the
      inhibitory effect observed in cell cultures treated with TNF-alpha at higher
      concentrations, but showed no effect on cell cultures treated with TNF-alpha at
      lower concentrations. In contrast, long-term treatment of TNF-alpha at all
      concentrations induced inhibitory effects on in vitro mineral nodule formation.
      MTT assay showed that TNF-alpha inhibits proliferation/survival of mesenchymal
      stem cells when the NF-kappaB signaling pathway is blocked. CONCLUSIONS: The
      binding of TNF-alpha to its receptors results in the activation of multiple
      signaling pathways, which actively interact with each other to regulate the
      differentiation, proliferation, survival and apoptosis of MSCs.

PMID- 21951286
TI  - Importance of Sox2 in maintenance of cell proliferation and multipotency of
      mesenchymal stem cells in low-density culture.
AB  - OBJECTIVES: This study has aimed to repopulate 'primitive' cells from late
      passage mesenchymal stem cells (MSCs) of poor multipotentiality and low cell
      proliferation rate, by simply altering plating density. MATERIALS AND METHODS:
      Effects of low density culture compared t high density culture on late-passage
      bone marrow (BM)-derived MSCs and pluripotency markers of multipotentiality were
      investigated. Cell proliferation, gene expression, RNA interference and
      differentiation potential were assayed. RESULTS AND CONCLUSIONS: We repopulated
      'primitive' cells by replating late-passage MSCs at low density (17 cells/cm(2) )
      regardless of donor age. Repopulated MSCs from low-density culture were smaller
      cells with spindle shaped morphology compared to MSCs from high-density culture.
      The latter had enhanced colony-forming ability, proliferation rate, and
      adipogenic and chondrogenic potential. Strong expression of osteogenic-related
      genes (Cbfa1, Dlx5, alkaline phosphatase and type Iota collagen) in late-passage
      MSCs was reduced by replating at low density, whereas expression of three
      pluripotency markers (Sox2, Nanog and Oct-4), Osterix and Msx2 reverted to levels
      of early-passage MSCs. Knockdown of Sox2 and Msx2 but not Nanog, using RNA
      interference, showed significant decrease in colony-forming ability.
      Specifically, knockdown of Sox2 significantly inhibited multipotentiality and
      cell proliferation. Our data suggest that plating density should be considered to
      be a critical factor for enrichment of 'primitive' cells from heterogeneous BM
      and that replicative senescence and multipotentiality of MSCs during in vitro
      expansion may be predominantly regulated through Sox2.

PMID- 21951287
TI  - Cholesterol synthesis-related enzyme oxidosqualene cyclase is required to
      maintain self-renewal in primary erythroid progenitors.
AB  - OBJECTIVES: Molecular mechanisms controlling cell fate decision making in self
      renewing cells are poorly understood. A previous transcriptomic study, carried
      out in primary avian erythroid progenitor cells (T2ECs), revealed that the gene
      encoding oxidosqualene cyclase (OSC/LSS), an enzyme involved in cholesterol
      biosynthesis, is significantly up-regulated in self-renewing cells. The aim of
      the present work is to understand whether this up-regulation is required for self
      renewal maintenance and what are the mechanisms involved. MATERIALS AND METHODS:
      To investigate OSC function, we studied effects of its enzymatic activity
      inhibition using Ro48-8071, a specific OSC inhibitor. In addition, we completed
      this pharmacological approach by RNAi-mediated OSC/LSS knockdown. The study of
      OSC inhibition was carried out on both self-renewing and differentiating cells to
      observe any state-dependent effect. RESULTS:   Our data show that OSC acts both
      by protecting self-renewing T2EC cells from apoptosis and by blocking their
      differentiation program, as OSC inhibition is sufficient to trigger spontaneous
      commitment of self-renewing cells towards an early differentiation state. This is
      self-renewal specific, as OSC inhibition has no effect on erythroid progenitors
      that have already differentiated. CONCLUSIONS: Taken together, our results
      suggest that OSC/LSS expression and activity are required to maintain cell self
      renewal and may be involved in the self-renewal versus differentiation/apoptosis
      decision making, by keeping cells in a self-renewal state.

PMID- 21951288
TI  - Ethyl acetate extract and its major constituent, isorhamnetin 3-O-rutinoside,
      from Nitraria retusa leaves, promote apoptosis of human myelogenous
      erythroleukaemia cells.
AB  - OBJECTIVE: Fractionation of ethyl acetate extract (EA) obtained from Nitraria
      retusa leaves was assessed using different methods of chromatography, and
      isorhamnetin3-O-rutinoside (I3-O-R) was isolated from this extract. Its structure
      was determined using data obtained from (1) H and (13) C NMR spectra, as well as
      by various correlation experiments (COSY, HMQC and HMBC). Both EA extract and I3
      O-R were investigated for their ability to induce apoptosis in human chronic
      myelogenous erythroleukaemia cells (K562). MATERIALS AND METHODS: Apoptosis of
      cells from the K562 line was detected by DNA fragmentation, PARP cleavage and by
      evaluating activities of caspases 3 and 8. RESULTS: Apoptosis, revealed by DNA
      fragmentation and PARP cleavage, was observed after 48-h incubation of these
      human myelogenous erythroleukaemia cells (K562), with the tested products.
      Likewise, caspase 3 and caspase 8 activities were induced in the presence of the
      EA extract and I3-O-R after 48 h of incubation. CONCLUSION: Our results strongly
      suggest the involvement of the extrinsic pathway of apoptosis in cells treated by
      both the original EA extract and its major component, I3-O-R.

PMID- 21951289
TI  - Expansion of human embryonic stem cells: a comparative study.
AB  - OBJECTIVES: Human embryonic stem cells (hESC) are promising for tissue
      engineering (TE) purposes due to their unique properties. However, current
      standard mechanical passaging techniques limit rates of possible TE experiments,
      as it is difficult to obtain high enough numbers of the cells for
      experimentation. In this study, several dissociative solutions and application
      methods are tested for their applicability to, and influence on, hESC culture and
      expansion. MATERIALS AND METHODS: Expansion of two hESC lines, H1 and VUB01,
      subjected to different passaging techniques, was evaluated. Four dissociative
      solutions - TrypLETM Express, Trypsin-EDTA, Cell Dissociation Solution and
      AccutaseTM- were combined with two application protocols. As reference
      conditions, manual and bead-based passaging techniques were used. RESULTS:
      Results showed that use of Cell Dissociation Solution in combination with a slow
      adaptation protocol, generated the best expansion profile for both cell lines.
      The hESC single cell lines remained pluripotent, had good expansion profiles and
      were capable of differentiation into representatives of all three germ layers.
      Reproducibility of the results was confirmed by adaptation for three other hESC
      lines. CONCLUSION: Use of Cell Dissociation Solution, combined with slow
      adaptation protocol, allows a fast switch from the mechanical passaging technique
      to a single-cell split technique, generating stable and robust hESC cell lines,
      which allow for large scale expansion of hESC for TE purposes.

PMID- 21951290
TI  - Effects of 4-nonylphenol on proliferation of AGS gastric cells.
AB  - OBJECTIVES: Nonylphenol (NP) is present ubiquitously in both aquatic and
      terrestrial environments. This compound is considered an important endocrine
      disruptor and its toxic/oestrogenic activity has been investigated in a number of
      in vitro and in vivo studies. Human exposure to NP may occur by cutaneous
      absorption, ingestion of contaminated food or water and inhalation. Moreover,
      while the cytotoxic effects of NP are known and studied, its effects on cell
      death and related mechanisms are not known. Our group decided to investigate NP
      effects on a gastric epithelial cell line (AGS), in particular NP effects on AGS
      cell cycle and apoptosis. MATERIALS AND METHODS: Cell cycle was analysed by flow
      cytometry, p21 and p27 induction, and apoptosis was analysed by flow cytometry
      and annexin-V assays, Fas, Fas-L, caspase 8 and caspase 3 activation. RESULTS: We
      have demonstrated that NP affected cell cycle and apoptosis in a time- and dose
      dependent manner, reaching the most notable effect at concentration of 10(-7)m,
      for 48 h. Flow cytometry revealed that treatment with 10(-7) m NP led to
      accumulation of cells at G(2) /M transition and increased percentage population
      of apoptotic cells. Results have shown that NP at concentration 10(-7) m induced
      marked increase in Fas and Fas-L expression. Moreover, 10(7) m NP induced
      activation of caspases 8 and 3, but not activation of caspase 9. CONCLUSIONS: The
      results reported suggest that gastric cells can be useful as screening population
      for appropriate study of developmental toxicity.

PMID- 21951292
TI  - Synthesis of well-defined head-to-tail-type oligothiophenes by regioselective
      deprotonation of 3-substituted thiophenes and nickel-catalyzed cross-coupling
      reaction.
AB  - Iterative growth of thiophene oligomers by single-step extensions has been
      realized by regioselective metalation of 3-substituted thiophenes with the
      Knochel-Hauser base (TMPMgCl.LiCl) and coupling with bromothiophene using a
      nickel catalyst. Treatment of 3-hexylthiophene with TMPMgCl.LiCl induces
      metalation at the 5-position selectively. Subsequent addition of 2-bromo-3
      hexylthiophene and a nickel catalyst leads to the corresponding bithiophene. The
      obtained bithiophene is converted to the terthiophene and then to the
      quaterthiophene by repeating the similar protocol. A concise synthesis of MK-1
      and MK-2, which are organic dye molecules bearing an oligothiophene moiety that
      are used in photovoltaic cells, has been achieved.

PMID- 21951291
TI  - Proliferation of dental follicle-derived cell populations in heat-stress
      conditions.
AB  - OBJECTIVES: Isolation and purification of adult stem cells (ASC) are a great
      challenge. Our objectives were to determine whether ASC are more heat-tolerant
      than non-stem cells, and to explore if ASC could be enriched by heat-stress
      treatments. MATERIALS AND METHODS: Rat dental follicle cells were cultured in a
      variety of media to obtain either a heterogeneous cell population (H-DFC)
      consisting of stem cells and non-stem cells, or a homogenous cell population
      (DFC) containing non-stem cells only. Real-time RT-PCR was conducted to compare
      expression of heat-shock proteins (HSPs) between the two populations. To study
      heat tolerance, H-DFC and DFC were incubated under heat-stress conditions and
      cell proliferation was evaluated by alamar blue reduction assay. Furthermore,
      cells resulting from heat-stress treatments were evaluated for differentiation
      capability and expression of stem cell markers. RESULTS: H-DFC expressed higher
      levels of HSP110, HSP70s and HSP27s than did DFC. H-DFC increased levels of
      proliferation at 40  degrees C compared to controls grown at 37  degrees C; no
      significant reduction in proliferation occurred at temperatures below 40.5 
      degrees C. In contrast, DFC showed significant reduction in proliferation under
      all heat-stress treatments. Heat-stressed H-DFC had increased differentiation
      capability and increased expression of stem cell markers. CONCLUSION: Stem cells
      appear to be more tolerant to heat stress than non-stem cells. Incubation of a
      heterogeneous cell population in heat-stress conditions resulted in increased
      stem cell numbers.

PMID- 21951293
TI  - EASI, (objective) SCORAD and POEM for atopic eczema: responsiveness and minimal
      clinically important difference.
AB  - BACKGROUND:   Demonstration of adequate reliability and validity is sufficient
      for concluding that an instrument is applicable for descriptive and predictive
      purposes, but before we can confidently use an outcome measure in clinical
      trials, the responsiveness (synonymous with sensitivity to change) and minimal
      clinically important difference (MCID) should be known. With this study, we aimed
      to assess responsiveness and MCID of four outcome measures used in atopic eczema:
      the Severity Scoring of Atopic Dermatitis (SCORAD), the objective SCORAD, Eczema
      Area and Severity Index (EASI), and the Patient-Oriented Eczema Measure (POEM).
      METHODS:   Data of three randomized controlled trials were used. To demonstrate
      responsiveness, we plotted receiver operating characteristic (ROC) curves. MCID
      was estimated using mean change scores of patients that showed a relevant
      improvement. Bland and Altman methods were used to quantify the limits of
      agreement. RESULTS:   Area under the ROC curve for the SCORAD was 0.70 [95%
      confidence interval (CI): 0.61-0.78], for the objective SCORAD, 0.73 (95% CI:
      0.70-0.77), for the EASI, 0.67 (95% CI: 0.60-0.76), and for the POEM, 0.67 (95%
      CI: 0.59-0.75). Scores above 0.70 represent a fair responsiveness. The MCID was
      8.7 points for the SCORAD, 8.2 for the objective SCORAD, 6.6 for the EASI, and
      3.4 for the POEM. CONCLUSION:   The objective SCORAD and SCORAD showed a fair
      responsiveness. The MCIDs are an important prerequisite for the interpretation of
      published eczema trials and for the planning/sample size estimation of future
      trials.

PMID- 21951294
TI  - A single nucleotide polymorphism rs9468925 of MHC region is associated with
      clinical features of generalized vitiligo in Chinese Han population.
AB  - BACKGROUND: Vitiligo has been found to be associated with different HLA antigens
      in different ethnic groups. In our previous genome-wide association study (GWAS),
      we identified independent association signal of rs9468925 (P = 2.21 * 10(-33), OR
      = 0.74) within HLA-C-HLA-B region. OBJECTIVES: To explore the association between
      rs9468925 polymorphism within MHC and the clinical features of generalized
      vitiligo. METHODS: The study, using 5566 cases and 6462 controls from previous
      GWA study investigated the single and combined (GA + GG) genotypic distribution
      of rs9468925 in subsets of vitiligo patients having different clinical features.
      We performed a QTL analysis (quantitative trait locus) for age of onset with
      genotype of rs9468925. RESULTS: The GA + GG genotypic distribution of SNP
      rs9468925 tested with an additive model was found to be significantly different
      in subgroups of patients of >20 vs. <20 years old (genotypic P = 2.57 * 10(-4),
      combined P = 3.0 * 10(-3), OR = 0.77, 95% CI: 0.64-0.92), and in patients with
      different clinical subtypes of vitiligo (genotypic P = 0.03, combined P = 5.0 *
      10(-3)). However, there was no statistical significance for familial history,
      halo nevi involvement and autoimmune disease involvement. CONCLUSIONS: Allele G
      of rs9468925 on HLA-C-HLA-B may be associated with a higher risk of vitiligo. Our
      study showed a significant genotypic variation between patients with age of onset
      <= 20 years and age of onset >20 years. Obvious clinical differences of
      generalized vitiligo related to genotypic variation found in the Chinese Han
      population were confirmed in this study.

PMID- 21951295
TI  - Gold(I)-catalyzed polycyclizations of polyenyne-type anilines based on
      hydroamination and consecutive hydroarylation cascade.
AB  - A hydroamination-double hydroarylation cascade using aniline derivatives bearing
      a trienyne moiety as the substrate was efficiently promoted by a gold(I) catalyst
      to produce benzo[a]naphtho[2,1-c]carbazole derivatives in good yields. This
      reaction is applicable to various substituted trienyne-type anilines, including
      2,3-diethynylthiophene derivatives. The reaction of anilines bearing a tetraenyne
      and pentaenyne moiety allows direct construction of highly fused carbazoles by
      tetra- and pentacyclization, respectively, through hydroamination and consecutive
      hydroarylation without producing any theoretical waste products from the
      substrates.

PMID- 21951296
TI  - Protist diversity in suboxic and sulfidic waters of the Black Sea.
AB  - The oxic-anoxic transition zone of the Black Sea comprises a large suboxic zone
      as well as anoxic and sulfidic waters. While the prokaryotes and biogeochemical
      cycles that characterize this zone have been frequently studied, little is known
      about the diversity or ecology of its microbial eukaryotes. Here, we present the
      first broad qualitative report of the protist species composition in the Black
      Sea redoxcline using molecular tools. Fingerprint analysis from the whole
      redoxcline revealed a complex community structure of metabolically active
      protists with distinct shifts along the redox gradient. Additionally, 18S rRNA
      gene clone libraries were used to compare protist species composition of suboxic
      and sulfidic water layers. Among the ciliates, sequences related to Pleuronema
      and Strombidium were dominant in both water layers whereas sequences affiliated
      with anaerobic plagiopylids and Cyclidium were detected only in the sulfidic
      zone. Among the flagellates, mainly stramenopiles (mostly bicosoecids and
      chrysophytes) occurred throughout the redoxcline. In the sulfidic zone we found
      stramenopile sequences but also euglenozoans, jakobids and choanoflagellates that
      were related to clonal sequences from other anoxic marine habitats, thus
      indicating the existence of globally distributed groups of anoxic flagellates.
      Higher species diversity in the sulfidic zone and about twice as many novel
      sequence types of ciliates and stramenopiles compared with the suboxic layer
      emphasizes the importance of anoxic, sulfidic waters as habitat for high protist
      diversity although the function of these organisms is yet unknown.

PMID- 21951298
TI  - A new experimental method for hiatal reinforcement using connective tissue patch
      transfer.
AB  - The closure of a large hiatal hernia still represents a challenge for the
      surgeon. Mesh reinforcement of a hiatoplasty generally decreases recurrence rate.
      An artificial mesh is cheaper compared with a biologic one, but has a higher
      complication rate. Our aim was to introduce a new biologic reinforcement method
      with less expenses. During organ donation for transplantation, tissue islets from
      pericardium and fascia lata were cryopreserved in a tissue bank. Later, the
      grafts were transplanted on the diaphragm of mongrel dogs. After 1, 3, and 6
      months, the animals were sacrificed, and the transplanted patches were
      macroscopically and microscopically examined. There were no macroscopic signs of
      inflammation, abcedation, or significant adhesion formation. The grafts were well
      recognizable, with palpable thickening and moderate shrinkage. Microscopically,
      an organization process with fibrosis, neovascularization, and peritoneal
      integration could be observed. Reinforcement of a hiatoplasty with connective
      tissue transfer either with cryopreserved or autologous tissue is a good option.
      This is a cheap and easy method, which should also be tested in human
      interventions.

PMID- 21951299
TI  - Glycoproteins are species-specific markers and major IgE reactants in grass
      pollens.
AB  - Grass pollen allergic patients are concomitantly exposed and sensitized to
      pollens from multiple Pooideae (i.e. common grass) species. As such, they are
      currently desensitized by allergen-specific immunotherapy using extracts made
      from mixes of pollens from Anthoxanthum odoratum, Dactylis glomerata, Lolium
      perenne, Phleum pratense and Poa pratensis. Herein, we demonstrate that species
      specific glycoprotein patterns are documented by 1D and 2D electrophoresis and
      Western blotting analysis, which can be used as an identity test for such
      pollens. Most allergens are glycoproteins bearing complex N-glycans encompassing
      beta1,2 xylose and alpha1,3 fucose glycoepitopes. Glycoepitope destruction using
      periodate oxidation has no impact on seric IgE reactivity in 75% atopic patients
      (n = 24). The latter have thus no significant IgE responses to carbohydrate
      containing epitopes. In contrast, periodate treatment strongly impairs IgE
      recognition of glycoallergens in 25% of patients tested, demonstrating the
      presence of carbohydrate-specific IgE in those patients. While the clinical
      impact of carbohydrate-specific IgE is still a matter of controversy, the
      presence of these IgE in the serum of many allergic patients illustrates the need
      for cross-reacting carbohydrate epitope-free recombinant allergens to develop
      relevant diagnostic tests. These data also support the pertinence of mixing
      multiple grass pollens to desensitize atopic patients, with the aim to broaden
      the repertoire of glycoepitopes in the vaccine, thus mimicking natural exposure
      conditions.

PMID- 21951300
TI  - Combining breast and cervical screening in an attempt to increase cervical
      screening uptake. An intervention study in a South African context.
AB  - During 2008-2009, only 4% of women targeted for cervical screening were screened
      in Tshwane, South Africa. The purpose of the study was to determine whether
      cervical screening uptake could be improved when breast and cervical screening
      are combined. An intervention research design was used. The intervention was
      assessed in terms of two outcomes, namely cervical screening uptake and the
      findings of the screening. The study was conducted in a resource poor environment
      in Tshwane. Convenience sampling was used to recruit the sample (n = 299) and a
      baseline survey was conducted before delivering the intervention. Only 14% of the
      sample (n = 299) reported having been screened for cervical cancer previously.
      The total sample (n = 299) were willing to have a clinical breast examination;
      however, only 65.4% of those eligible for cervical screening (n = 283) used the
      opportunity to be screened. The majority of the sample screened (n = 185) using
      acetic acid for visual inspection (VIA) were VIA negative; 12.4% were VIA
      positive and 4.4% were VIA positive, invasive cancer; the screening of 8.7%
      failed. Despite women's lack of knowledge of cervical cancer and the screening
      thereof, combining cervical screening and breast screening lead to an increase in
      cervical screening uptake.

PMID- 21951301
TI  - Protective effects of mineralocorticoid receptor blockade against neuropathy in
      experimental diabetic rats.
AB  - AIMS: Mineralocorticoid receptor (MR) blockade is an effective treatment for
      hypertension and diabetic nephropathy. There are no data on the effects of MR
      blockade on diabetic peripheral neuropathy (DPN). The aim of this study was to
      determine whether MRs are present in the peripheral nerves and to investigate the
      effectiveness of MR blockade on DPN in streptozotocin (STZ)-induced diabetic
      rats. METHODS: Expression of MR protein and messenger RNA (mRNA) was examined in
      the peripheral nerves using Western blot analysis and RT-PCR. We next studied the
      effects of the selective MR antagonist eplerenone and the angiotensin II receptor
      blocker candesartan on motor and sensory nerve conduction velocity (NCV),
      morphometric changes and cyclooxygenase-2 (COX-2) gene and NF-kappaB protein
      expression in the peripheral nerves of STZ-induced diabetic rats. RESULTS:
      Expression of MR protein and mRNA in peripheral nerves was equal to that in the
      kidney. Motor NCV was significantly improved by 8 weeks of treatment with either
      eplerenone (39.1 +/- 1.2 m/s) or candesartan (46.4 +/- 6.8 m/s) compared with
      control diabetic rats (33.7 +/- 2.0 m/s) (p < 0.05). Sensory NCV was also
      improved by treatment with candesartan or eplerenone in diabetic rats. Eplerenone
      and candesartan caused significant improvement in mean myelin fibre area and mean
      myelin area compared with control diabetic rats (p < 0.05). COX-2 mRNA and NF
      kappaB protein were significantly elevated in the peripheral nerves of diabetic
      rats compared with control rats, and treatment with eplerenone or candesartan
      reduced these changes in gene expression (p < 0.05). CONCLUSION: MR blockade may
      have neuroprotective effects on DPN.

PMID- 21951302
TI  - Protein kinase C alpha and beta are positive regulators of thrombus formation in
      vivo in a zebrafish (Danio rerio) model of thrombosis.
AB  - BACKGROUND: The zebrafish (Danio rerio) is becoming an attractive model organism
      for the assessment of gene function in thrombosis in vivo. Zebrafish, as a
      thrombosis model, have several advantages, with the capacity to follow thrombus
      formation at high resolution in real time using intravital microscopy, without
      the need for complex surgical techniques, and the capability to rapidly knockdown
      gene expression using morpholino antisense approaches. OBJECTIVES: We have
      recently shown, in mouse models, that protein kinase C alpha (PKCalpha) plays a
      critical role in regulating thrombus formation in vivo. PKC beta (beta) plays a
      non-redundant role also in platelet function in vitro, but the function of this
      gene had not yet been assessed in vivo. METHODS: In the present study, we
      analyzed the function of both PKCalpha and PKCbeta in the zebrafish model in
      vivo, by live imaging using a laser-induced injury of the main caudal artery in 3
      day-old larvae. RESULTS: We showed that D. rerio express orthologs of both the
      PKCalpha and PKCbeta genes, with high sequence identity. Translation blocking and
      splice-blocking morpholinos effectively and specifically knockdown expression of
      these genes and knockdown with either morpholino leads to attenuated thrombus
      formation, as assessed by several quantitative parameters including time to
      initial adhesion and peak thrombus surface area. CONCLUSIONS: Our data indicate
      that these two highly related genes play non-redundant roles in regulating
      thrombosis, an observation that supports our previous in vitro murine data, and
      suggests unique roles, and possibly unique regulation, for PKCalpha and PKCbeta
      in controlling platelet function in vivo.

PMID- 21951303
TI  - Significance of microbleeds in patients with transient ischaemic attack.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to determine the prognostic
      significance of microbleeds in TIA-patients. In patients with a transient
      ischaemic attack (TIA), the prognostic value of microbleeds is unknown. METHODS:
      In 176 consecutive TIA patients, the number, size, and location of microbleeds
      with or without acute ischaemic lesions were assessed. We compared microbleed
      positive and microbleed-negative patients with regard to the end-point stroke
      within 3 months. RESULTS: Four of the seven patients with subsequent stroke had
      microbleeds. Microbleed-positive patients had a higher risk for stroke [odds
      ratios (OR) 8.91, 95% CI 1.87-42.51, P<0.01] than those without microbleeds.
      Microbleed-positive patients with accompanying acute ischaemic lesions had a
      higher stroke risk than those with neither an acute ischaemia nor a microbleed
      (OR 6.20, 95% CI 1.10-35.12; P=0.04). CONCLUSION: Microbleeds alone or in
      combination with acute ischaemic lesions may increase the risk for subsequent
      ischaemic stroke after TIA within 3 months.

PMID- 21951304
TI  - Analysis of psoriasis patients registered with the Japanese Society for Psoriasis
      Research from 2002-2008.
AB  - A survey of psoriasis patients from 1982-2001 has been reported by the Japanese
      Society for Psoriasis Research. The aim of this study is to analyze psoriasis
      patients in Japan registered from 2002-2008. A total of 11 631 cases were
      registered from 152 dermatological institutions in Japan. Males (7738 cases,
      66.5%) were predominant over females (3893 cases, 33.5%). The clinical types of
      psoriasis were psoriasis vulgaris (88.5%), guttate psoriasis (3.9%), psoriasis
      arthropathica (3.3%), generalized pustular psoriasis (1.3%), psoriatic
      erythroderma (1.2%), localized pustular psoriasis (0.9%) and infantile psoriasis
      (0.1%). Topical corticosteroids (85.4%) and vitamin D(3) (59.7%) products were
      the main previous topical agents. Previous systemic treatments included
      etretinate (8.8%), cyclosporin (8.3%) and methotrexate (2.0%). Use of topical
      vitamin D(3) and systemic cyclosporin therapies has been increasing during the
      past 7 years. Topical psoralen and ultraviolet A therapy (PUVA) (7.6%) was the
      predominant phototherapy followed by UV-B (7.3%) and systemic PUVA (4.7%). Use of
      UV-B phototherapy has been increasing during the past 5 years. The survey of
      Japanese psoriasis patients during 2002-2008 disclosed that psoriasis
      arthropathica is more prevalent (1%) than that of the previous survey during 1982
      2001. Use of topical vitamin D(3) and systemic cyclosporin has been increasing
      during the past 7 years.

PMID- 21951305
TI  - The caries-preventive effect of xylitol/maltitol and erythritol/maltitol
      lozenges: results of a double-blinded, cluster-randomized clinical trial in an
      area of natural fluoridation.
AB  - OBJECTIVE: Xylitol studies suggest caries reductions in the order of 50%. Based
      on animal/microbial studies, erythritol potentially has caries-preventive
      properties. However, clinical studies are required to confirm this. The aim of
      the study was to investigate the additional caries-preventive effect of
      xylitol/maltitol and erythritol/maltitol lozenges delivered at school, relative
      to controls receiving comprehensive prevention, in a low-caries prevalence
      population. METHODS: A 4-year, cluster-randomized, double-blinded clinical trial.
      Five hundred and seventy-nine 10-year-old consenting subjects from 21 schools
      were randomly assigned to one of five groups. Four groups used the lozenges on
      school days, in three teacher-supervised sessions daily, over 1 or 2 years. The
      daily amount was 4.7 g/4.6 g for xylitol/maltitol and 4.5 g/4.2 g for
      erythritol/maltitol. The groups received free examinations and care in the public
      health centre. Four hundred and ninety-six children were analysed. The main
      outcome measure was dentin caries increment based on a clinical examination at 4
      years since the start. The groups were compared in relation to the increment
      using hierarchical logistic regression to adjust for potential clustering.
      RESULTS: Use of xylitol/maltitol or erythritol/maltitol lozenges did not result
      in caries reduction. A strong relationship between baseline caries prevalence and
      the 4-year increment was observed (OR = 7.38; 95% CI: 3.78-14.41). CONCLUSIONS:
      The results suggest that in relatively low-caries conditions the school-based use
      of xylitol/maltitol or erythritol/maltitol lozenges would not have additional
      caries-preventive effect when compared with comprehensive prevention.

PMID- 21951306
TI  - Costs, equity, efficiency and feasibility of identifying the poor in Ghana's
      National Health Insurance Scheme: empirical analysis of various strategies.
AB  - OBJECTIVES: To analyse the costs and evaluate the equity, efficiency and
      feasibility of four strategies to identify poor households for premium exemptions
      in Ghana's National Health Insurance Scheme (NHIS): means testing (MT), proxy
      means testing (PMT), participatory wealth ranking (PWR) and geographic targeting
      (GT) in urban, rural and semi-urban settings in Ghana. METHODS: We conducted the
      study in 145-147 households per setting with MT as our gold standard strategy. We
      estimated total costs that included costs of household surveys and cost of
      premiums paid to the poor, efficiency (cost per poor person identified), equity
      (number of true poor excluded) and the administrative feasibility of
      implementation. RESULTS: The cost of exempting one poor individual ranged from
      US$15.87 to US$95.44; exclusion of the poor ranged between 0% and 73%. MT was
      most efficient and equitable in rural and urban settings with low-poverty
      incidence; GT was efficient and equitable in the semi-urban setting with high
      poverty incidence. PMT and PWR were less equitable and inefficient although
      feasible in some settings. CONCLUSION: We recommend MT as optimal strategy in low
      poverty urban and rural settings and GT as optimal strategy in high-poverty semi
      urban setting. The study is relevant to other social and developmental programmes
      that require identification and exemptions of the poor in low-income countries.

PMID- 21951307
TI  - Analysis of axon guidance defects at the optic chiasm in heparan sulphate
      sulphotransferase compound mutant mice.
AB  - During embryonic development of the visual system, retinal ganglion cells (RGCs)
      project their axons towards the brain, passing through the optic chiasm. Axons
      are guided on this journey by molecular cues in the environment. The heparan
      sulphate sulphotransferase (Hst) enzymes Hs2st and Hs6st1 are each known to be
      required for specific aspects of axon guidance in the developing visual system,
      as revealed by studies of Hs2st(-/-)  and Hs6st1(-/-)  mutant embryos. However,
      it remained possible that these two enzymes have additional, overlapping,
      functions in RGC axon guidance; but that no effect is manifest in single mutant
      embryos, because the other enzyme is sufficient to fulfil the shared function. To
      investigate this possibility, we generated a set of Hs2st;Hs6st1 double mutant
      embryos that had reduced gene dosage of each of these Hsts, reasoning that any
      additional phenotypes in these animals would indicate the presence of functional
      overlap. We first characterised the structure of the mutant Hs6st1 locus,
      identifying the insertion site of the gene trap vector, to allow us to genotype
      compound mutants reliably. We found that Hs2st(-/-) ;Hs6st1(-/-)  mutants that
      lack both enzymes died prior to E15.5. As the optic chiasm has not formed by this
      stage, we were unable to determine the effect of complete loss of Hs2st and
      Hs6st1 on chiasm formation. However, compound mutant embryos lacking one Hst and
      heterozygous for the other were viable. We found that RGC axon guidance defects
      in such compound mutants were no more severe than those found in the single
      mutant embryos. We also found that expression of the Hs6st1 isoform Hs6st3
      overlaps with that of Hs6st1 in the developing visual system, suggesting that
      some Hs6st activity remains present in this region of Hs6st1(-/-)  mutant
      embryos.

PMID- 21951308
TI  - Pregravid body mass index, psychological factors during pregnancy and
      breastfeeding duration: is there a link?
AB  - Breastfeeding rates in the United States are low, and one possible reason may be
      the high prevalence of overweight/obesity among women of childbearing age. This
      analysis examined the association between pregravid body mass index and
      breastfeeding duration, and explored whether depressive symptoms, perceived
      stress and anxiety during pregnancy mediated this relationship. Participants (n =
      550) in the Pregnancy, Infection and Nutrition Postpartum Study were recruited
      through prenatal clinics prior to 20 weeks gestation and followed to 12 months
      post-partum. Duration of any breastfeeding was categorized as none, less than 4
      months, 4-6 months, 7-12 months and more than 12 months (referent). Exclusive
      breastfeeding was categorized as less than 1 month, 1 to less than 4 months and 4
      months or more (referent). Being overweight/obese before pregnancy (35.7% of 550)
      was inversely associated with the durations of any and exclusive breastfeeding.
      Women who entered pregnancy overweight or obese were more likely to not initiate
      breastfeeding [relative risk ratio (RRR)=5.39 (95% confidence interval: 2.41,
      12.04)] and to breastfeed less than 4 months [RRR=2.38 (1.33, 4.27)] compared
      with women of normal weight status. Among women who initiated breastfeeding,
      being overweight or obese vs. normal weight was related to exclusively
      breastfeeding less than 1 month [RRR=2.09 (1.24, 3.51)]. We did not find evidence
      to support mediation by depressive symptoms, perceived stress or anxiety during
      pregnancy. Future research needs to explore the reasons behind the association
      between overweight/obesity and breastfeeding duration.

PMID- 21951310
TI  - Physiological roles of microglia during development.
AB  - In all the species examined thus far, the behavior of microglia during
      development appears to be highly stereotyped. This reproducibility supports the
      notion that these cells have a physiological role in development. Microglia are
      macrophages that migrate from the yolk sac and colonize the central nervous
      system early during development. The first invading yolk-sac macrophages are
      highly proliferative and their role has not yet been addressed. At later
      developmental stages, microglia can be found throughout the brain and tend to
      preferentially reside at specific locations that are often associated with known
      developmental processes. Thus, it appears that microglia concentrate in areas of
      cell death, in proximity of developing blood vessels, in the marginal layer,
      which contains developing axon fascicles, and in close association with radial
      glial cells. This review describes the main features of brain colonization by
      microglia and discusses the possible physiological roles of these cells during
      development.

PMID- 21951311
TI  - A novel model to predict cutaneous finger blood flow via finger and rectal
      temperatures.
AB  - OBJECTIVES: To generate a model that predicts fingertip blood flow (BF(f) ) and
      to cross-validate it in another group of subjects. METHODS: We used fingertip
      temperature (T(f)), forearm temperature minus T(f) (T(For-f)), rectal temperature
      (T(re)), and their changes across time ((lag) T) to estimate BF(f). Ten
      participants (six male, four female) were randomly divided into "model" and
      "validation" groups. We employed a passive hot-cold water immersion protocol
      during which each participant's core temperature increased and decreased by 0.5
      degrees C above/below baseline during hot/cold conditions, respectively. A
      hierarchical multiple linear regression analysis was introduced to generate
      models using temperature indicators and (lag) T (independent variables) obtained
      from the model group to predict BF(f) (dependent variable). RESULTS: Mean BF(f)
      (109.5 +/- 158.2 PU) and predicted BF(f) (P-BF(f)) (111.4 +/- 136.7 PU) in the
      model group calculated using the strongest (R(2) = 0.766, p < 0.001) prediction
      model [P-BF(f) =T(f) * 19.930 + (lag4) T(f) * 74.766 + (lag4) T(re) * 124.255 -
      447.474] were similar (p = 0.6) and correlated (r = 0.880, p < 0.001).
      Autoregressive integrated moving average time-series analyses demonstrated a
      significant association between P-BF(f) and BF(f) (R(2) = 0.381; Ljung-Box
      statistic = 8.097; p < 0.001) in the validation group. CONCLUSIONS: We provide a
      model that predicts BF(f) via two practical temperature indicators that can be
      implemented in both clinical and field settings.

PMID- 21951309
TI  - Anti-obesity efficacy of LH-21, a cannabinoid CB(1)  receptor antagonist with
      poor brain penetration, in diet-induced obese rats.
AB  - BACKGROUND AND PURPOSE: Peripheral blockade of cannabinoid CB(1) receptors has
      been proposed as a safe and effective therapy against obesity, putatively devoid
      of the adverse psychiatric side effects of centrally acting CB(1) receptor
      antagonists. In this study we analysed the effects of LH-21, a peripherally
      acting neutral cannabinoid receptor antagonist with poor brain penetration, in an
      animal model of diet-induced obesity. EXPERIMENTAL APPROACH: To induce obesity,
      male Wistar rats were fed a high-fat diet (HFD; 60 kcal% fat) whereas controls
      received a standard diet (SD; 10 kcal% fat). Following 10 weeks of feeding,
      animals received a daily i.p. injection of vehicle or 3 mg.kg(-1) LH-21 for 10
      days. Plasma and liver samples were used for biochemical analyses whereas
      visceral fat-pad samples were analysed for lipid metabolism gene expression using
      real-time RT-PCR. In addition, the potential of LH-21 to interact with hepatic
      cytochrome P450 isoforms and cardiac human Ether-a-go-go Related Gene (hERG)
      channels was evaluated. KEY RESULTS: LH-21 reduced feeding and body weight gain
      in HFD-fed animals compared with the control group fed SD. In adipose tissue,
      this effect was associated with decreased gene expression of: (i) leptin; (ii)
      lipogenic enzymes, including SCD-1; (iii) CB(1) receptors; and (iv) both
      PPARalpha and PPARgamma. Although there were no significant differences in plasma
      parameters between HFD- and SD-fed rats, LH-21 did not seem to induce hepatic,
      cardiac or renal toxicity. CONCLUSIONS AND IMPLICATIONS: These results support
      the hypothesis that treatment with the peripherally neutral acting CB(1) receptor
      antagonist, LH-21, may promote weight loss through modulation of visceral adipose
      tissue.

PMID- 21951312
TI  - Rapid reduction of hepatitis C virus-Core protein in the peripheral blood improve
      the immunological response in chronic hepatitis C patients.
AB  - AIM:   The extracellular hepatitis C virus (HCV)-antigen, including HCV-Core
      protein, can suppress immune cells. Recently, the efficacy of double filtration
      plasmapheresis (DFPP) for chronic hepatitis C (CHC) was reported. However, the
      mechanism of efficacy of DFPP might not be only the reduction of HCV but also the
      effect of immune cells via direct and/or indirect mechanisms. The aim of this
      study is to analyze the virological and immunological parameters of difficult-to
      treat HCV patients treated with DFPP combined with Peg-interferon and RBV
      (DFPP/Peg-IFN/RBV) therapy. METHODS:   Twelve CHC patients were enrolled and
      treated with DFPP/Peg-IFN/RBV therapy. The immunological, virological and genetic
      parameters were studied. RESULTS:   All patients (4/4) treated with the major
      IL28B allele (T/T) could achieve complete early virological response (EVR). The
      amounts of HCV-Core antigen in the peripheral blood of EVR patients treated with
      DFPP/Peg-IFN/RBV rapidly declined in comparison to those of late virological
      response (LVR) patients treated with DFPP/Peg-IFN/RBV and EVR patients treated
      with Peg-IFN and RBV (Peg-IFN/RBV). The amount of IFN-gamma produced from
      peripheral blood gradually increased. On the other hand, the amount of IL10
      gradually decreased in the EVR patients. The frequencies of HCV-Core binding on
      CD3+ T cells rapidly declined in EVR patients treated with DFPP/Peg-IFN/RBV
      therapy. Moreover, the distributions of activated CD4(+) and CD8(+)  T cells and
      CD16-CD56 high natural killer cells were significantly changed between before and
      after DFPP. CONCLUSIONS:   The rapid reduction of HCV-Core antigens and changes
      in the distribution of lymphoid cells could contribute to the favorable
      immunological response during DFPP/Peg-IFN/RBV therapy.

PMID- 21951313
TI  - Intravitreal bevacizumab versus ranibizumab for the treatment of retinal
      angiomatous proliferation.
AB  - PURPOSE: To evaluate the effects of intravitreal bevacizumab and ranibizumab
      treatments in retinal angiomatous proliferation (RAP). METHODS: Fifty patients
      affected by RAP were randomly assigned either to intravitreal bevacizumab
      injection (IVBI) or intravitreal ranibizumab injection (IVRI). After a loading
      phase including three consecutive monthly injections, the retreatment was
      administered in cases of persistent RAP. The primary outcome measures were the
      mean changes in BCVA between the two treatment groups, and the proportion of eyes
      gaining 1 and 3 lines at the end of the follow-up. Secondary outcomes included
      central macular thickness (CMT) changes and progression to more advanced stages
      of RAP. RESULTS: Fifty patients affected by stage 1 and 2 RAP were recruited.
      Twenty-six and 24 patients received IVBI and IVRI, respectively. At the baseline,
      mean best corrected visual acuity (BCVA) values were 0.59 +/- 0.21 (LogMAR +/-
      SD, approximately corresponding to 20/80 Snellen Equivalent-SE) in IVBI group and
      0.66 +/- 0.33 (approximately 20/90 SE) in IVRI group with no statistical
      difference. At 12-month examination, both groups showed a statistically
      significant improvement in the BCVA, with a final mean value of 0.43 +/- 0.24
      (approximately 20/54 SE) in IVBI group and 0.50 +/- 0.32 (approximately 20/63 SE)
      in the IVRI group. A BCVA gain of 1 and 3 lines was registered in 20 and 8 eyes,
      respectively, in the IVBI group. Similarly, 17 and 7 eyes showed an improvement
      of 1 or 3 lines, respectively, in the IVRI group. The CMT reduced significantly
      from baseline to 12-month examination in both groups. A lower proportion of eyes
      with complete pigment epithelium detachment resolution was noted in the IVBI
      group than in the IVRI group (40% versus 90%). CONCLUSIONS: Our study shows that
      both IVBI and IVRI are equally effective in improving the BCVA over a 1-year
      follow-up in eyes affected by stage 1 and 2 RAP.

PMID- 21951314
TI  - Effect of mucosal TRPV1 inhibition in allergic rhinitis.
AB  - Transient receptor potential vanilloid-1 (TRPV1) has been implicated as a
      mediator of itch in allergic rhinitis. To address this possibility, we
      synthesized a TRPV1 blocker (SB-705498) for nasal administration in patients with
      seasonal allergic rhinitis. The pharmacological activity of SB-705498 was
      confirmed on human TRPV1-expressing HEK293 cells, using fluorometric calcium
      imaging, and in patients with allergic rhinitis subjected to nasal capsaicin
      challenges. The effect of SB-705498 was studied in patients with seasonal
      allergic rhinitis subjected to daily allergen challenges for 7 days, using a
      double-blind, placebo-controlled, randomized and cross-over design. SB-705498 was
      delivered by nasal lavage 2 min. before each allergen challenge. Primary end
      point was total nasal symptom score on days 5-7. Nasal peak inspiratory flow
      (nPIF) and eosinophil cationic protein (ECP) content in nasal lavages were also
      monitored. Daily topical applications of SB-705498 at a concentration that
      inhibited capsaicin-induced nasal symptoms had no effect on total symptom score,
      nPIF and ECP levels in allergen-challenged patients with seasonal allergic
      rhinitis. The individual symptoms, nasal itch or sneezes, were also not affected.
      These findings may indicate that TRPV1 is not a key mediator of the symptoms in
      allergic rhinitis. However, additional studies, using drug formulations with a
      prolonged duration of action, should be conducted before TRPV1 is ruled out as a
      drug target in allergic rhinitis.

PMID- 21951315
TI  - Relationships between hair growth rate and morphological parameters of human
      straight hair: a same law above ethnical origins?
AB  - After measurement of individual growth rates, natural hair fibres from Asian and
      Caucasian subjects were analysed using scanning electron microscopy. In total,
      more than 1000 hairs were analysed. Measurements of diameter, medulla and
      interscale distance (average distance between two successive cuticle scales) show
      these parameters strongly correlated with hair growth rate. A thicker hair fibre
      corresponds to a faster growth rate, a shorter interscale distance and greater
      probability to have a medulla, and vice versa, a thin hair fibre shows slower
      growth rate, a larger interscale distance and a lower probability to have a
      medulla. Very interestingly, this finding appears to be unrelated to the ethnic
      origin of the subjects, suggesting a common characteristic of human hair, at
      least for the straight or semi-straight hair studied. From a practical viewpoint,
      this finding clearly suggests an alternative method for measuring hair growth
      rates, by measuring the interscale distance, which appears easier than using
      common laboratory equipments.

PMID- 21951316
TI  - Reducing Vibrio load in Artemia nauplii using antimicrobial photodynamic therapy:
      a promising strategy to reduce antibiotic application in shrimp larviculture.
AB  - We propose antimicrobial photodynamic therapy (aPDT) as an alternative strategy
      to reduce the use of antibiotics in shrimp larviculture systems. The growth of a
      multiple antibiotic resistant Vibrio harveyi strain was effectively controlled by
      treating the cells with Rose Bengal and photosensitizing for 30 min using a
      halogen lamp. This resulted in the death of >50% of the cells within the first 10
      min of exposure and the 50% reduction in the cell wall integrity after 30 min
      could be attributed to the destruction of outer membrane protein of V. harveyi by
      reactive oxygen intermediates produced during the photosensitization. Further,
      mesocosm experiments with V. harveyi and Artemia nauplii demonstrated that in 30
      min, the aPDT could kill 78.9% and 91.2% of heterotrophic bacterial and Vibrio
      population respectively. In conclusion, the study demonstrated that aPDT with its
      rapid action and as yet unreported resistance development possibilities could be
      a propitious strategy to reduce the use of antibiotics in shrimp larviculture
      systems and thereby, avoid their hazardous effects on human health and the
      ecosystem at large.

PMID- 21951317
TI  - Parotid gland-recovery after radiotherapy in the head and neck region--36 months
      follow-up of a prospective clinical study.
AB  - BACKGROUND: The aim of the present study was to evaluate the recovery potential
      of the parotid glands after using either 3D-conformal-radiotherapy (3D-CRT) or
      intensity-modulated radiotherapy (IMRT) by sparing one single parotid gland.
      METHODS: Between 06/2002 and 10/2008, 117 patients with head and neck cancer were
      included in this prospective, non-randomised clinical study. All patients were
      treated with curative intent. Salivary gland function was assessed by measuring
      stimulated salivary flow at the beginning, during and at the end of radiotherapy
      as well as 1, 6, 12, 24, and 36 months after treatment. Measurements were
      converted to flow rates and normalized relative to rates before treatment. Mean
      doses (D(mean)) were calculated from dose-volume histograms based on computed
      tomographies of the parotid glands. RESULTS: Patients were grouped according to
      the D(mean) of the spared parotid gland having the lowest radiation exposure:
      Group I - D(mean) < 26 Gy (n = 36), group II - D(mean) 26-40 Gy (n = 45), and
      group III - D(mean) > 40 Gy (n = 36). 15/117 (13%) patients received IMRT. By
      using IMRT as compared to 3D-CRT the D(mean) of the spared parotid gland could be
      significantly reduced (D(mean) IMRT vs. 3D-CRT: 21.7 vs. 34.4 Gy, p < 0.001). The
      relative salivary flow rates (RFSR) as a function of the mean parotid dose after
      24 and 36 months was in group I 66% and 74%, in group II 56% and 49%, and in
      group III 31% and 24%, respectively. Multiple linear regression analyses revealed
      that the parotid gland dose and the tumor site were the independent determinants
      12 and 36 months after the end of RT. Patients of group I and II parotid gland
      function did recover at 12, 24, and 36 months after the end of RT. CONCLUSIONS:
      If a D(mean) < 26 Gy for at least one parotid gland can be achieved then this is
      sufficient to reach complete recovery of pre-RT salivary flow rates. The
      radiation volume which depends on tumor site did significantly impact on the
      D(mean) of the parotids, and thus on the saliva flow and recovery of parotid
      gland.

PMID- 21951318
TI  - Ligand-dependent differences in estrogen receptor beta-interacting proteins
      identified in lung adenocarcinoma cells corresponds to estrogenic responses.
AB  - BACKGROUND: A recent epidemiological study demonstrated a reduced risk of lung
      cancer mortality in breast cancer patients using antiestrogens. These and other
      data implicate a role for estrogens in lung cancer, particularly nonsmall cell
      lung cancer (NSCLC). Approximately 61% of human NSCLC tumors express nuclear
      estrogen receptor beta (ERbeta); however, the role of ERbeta and estrogens in
      NSCLC is likely to be multifactorial. Here we tested the hypothesis that proteins
      interacting with ERbeta in human lung adenocarcinoma cells that respond
      proliferatively to estradiol (E2) are distinct from those in non-E2-responsive
      cells. METHODS: FLAG affinity purification of FLAG-ERbeta-interacting proteins
      was used to isolate ERbeta-interacting proteins in whole cell extracts from E2
      proliferative H1793 and non-E2-proliferative A549 lung adenocarcinoma cell lines.
      Following trypsin digestion, proteins were identified using liquid chromatography
      electrospray ionization tandem mass spectrometry (LC-MS/MS). Proteomic data were
      analyzed using Ingenuity Pathway Analysis. Select results were confirmed by
      coimmunoprecipitation. RESULTS: LC-MS/MS identified 27 non-redundant ERbeta
      interacting proteins. ERbeta-interacting proteins included hsp70, hsp60,
      vimentin, histones and calmodulin. Ingenuity Pathway Analysis of the ERbeta
      interacting proteins revealed differences in molecular and functional networks
      between H1793 and A549 lung adenocarcinoma cells. Coimmunoprecipitation
      experiments in these and other lung adenocarcinoma cells confirmed that ERbeta
      and EGFR interact in a gender-dependent manner and in response to E2 or EGF.
      BRCA1 interacted with ERbeta in A549 cell lines and in human lung adenocarcinoma
      tumors, but not normal lung tissue. CONCLUSION: Our results identify specific
      differences in ERbeta-interacting proteins in lung adenocarcinoma cells
      corresponding to ligand-dependent differences in estrogenic responses.

PMID- 21951319
TI  - Comparing school environments with and without legislation for the prevention and
      management of anaphylaxis.
AB  - BACKGROUND:   School personnel in contact with students with life-threatening
      allergies often lack necessary supports, creating a potentially dangerous
      situation. Sabrina's Law, the first legislation in the world designed to protect
      such children, requires all Ontario public schools to have a plan to protect
      children at risk. Although it has captured international attention, the
      differences a legislative approach makes have not been identified. Our study
      compared the approaches to anaphylaxis prevention and management in schools with
      and without legislation. METHODS:   Legislated (Ontario) and nonlegislated
      (Alberta, British Columbia, Newfoundland and Labrador, and Quebec) environments
      were compared. School board anaphylaxis policies were assessed for consistency
      with Canadian anaphylaxis guidelines. Parents of at-risk children and school
      personnel were surveyed to determine their perspectives on school practices.
      School personnel's EpiPen5 technique was assessed. RESULTS:   Consistency of
      school board policies with anaphylaxis guidelines was significantly better in a
      legislated environment (P=0.009). Parents in a legislated environment reported
      more comprehensive anaphylaxis emergency forms (P<0.001), while school personnel
      in nonlegislated environments reported more comprehensive forms (P=0.004).
      Despite school personnel in both environments receiving EpiPen5 training (>80%),
      suboptimal technique was commonly observed. However, school personnel in the
      legislated environment had better technique (P<0.001). CONCLUSION:   Our results
      suggest that school boards in legislated environments have made greater efforts
      to support students at risk for anaphylaxis compared to nonlegislated
      environments. However, significant gaps exist in both environments, especially
      with respect to EpiPen5 administration, content, and distribution of anaphylaxis
      emergency forms, and awareness of school procedures by school personnel and
      parents.

PMID- 21951320
TI  - A multilevel investigation of inequalities in clinical and psychosocial outcomes
      for women after breast cancer.
AB  - BACKGROUND: In Australia, breast cancer is the most common cancer affecting
      Australian women. Inequalities in clinical and psychosocial outcomes have existed
      for some time, affecting particularly women from rural areas and from areas of
      disadvantage. We have a limited understanding of how individual and area-level
      factors are related to each other, and their associations with survival and other
      clinical and psychosocial outcomes. METHODS/DESIGN: This study will examine
      associations between breast cancer recurrence, survival and psychosocial outcomes
      (e.g. distress, unmet supportive care needs, quality of life). The study will use
      an innovative multilevel approach using area-level factors simultaneously with
      detailed individual-level factors to assess the relative importance of
      remoteness, socioeconomic and demographic factors, diagnostic and treatment
      pathways and processes, and supportive care utilization to clinical and
      psychosocial outcomes. The study will use telephone and self-administered
      questionnaires to collect individual-level data from approximately 3, 300 women
      ascertained from the Queensland Cancer Registry diagnosed with invasive breast
      cancer residing in 478 Statistical Local Areas Queensland in 2011 and 2012. Area
      level data will be sourced from the Australian Bureau of Statistics census data.
      Geo-coding and spatial technology will be used to calculate road travel distances
      from patients' residence to diagnostic and treatment centres. Data analysis will
      include a combination of standard empirical procedures and multilevel modelling.
      DISCUSSION: The study will address the critical question of: what are the
      individual- or area-level factors associated with inequalities in outcomes from
      breast cancer? The findings will provide health care providers and policy makers
      with targeted information to improve the management of women with breast cancer,
      and inform the development of strategies to improve psychosocial care for women
      with breast cancer.

PMID- 21951321
TI  - A new approach to model the spatiotemporal development of biofilm phase in porous
      media.
AB  - Bacteria can exist within biofilms that are attached to the solid matrix of a
      porous medium. Under certain conditions, the biomass can fully occupy the pore
      space leading to reduced hydraulic conductivity and mass transport. Here, by
      treating biofilm as a growing, high-viscosity phase, a novel macroscopic approach
      to model biofilm spatial expansion and its corresponding effects on porous medium
      hydraulic properties is presented. The separate yet coupled flow of the water and
      biofilm phases is handled by using relative permeability curves that allow for
      biofilm movement within the porous medium and bioclogging effects. Fluid flow is
      governed by Darcy's law and component transport is set by the convection
      diffusion equation reaction terms for each component. Here, the system of
      governing equations is solved by using a commercial multiphase flow reservoir
      simulator, which is used to validate the model against published laboratory
      experiments. A comparison of the model and experimental observations reveal that
      the model provides a reasonable means to predict biomass development in the
      porous medium. The results reveal that coupled flow of water and movement of
      biofilm, as described by relative permeability curves, is complex and has a large
      impact on the development of biomass and consequent bioclogging in the porous
      medium.

PMID- 21951322
TI  - Outcome effectiveness of the severe sepsis resuscitation bundle with addition of
      lactate clearance as a bundle item: a multi-national evaluation.
AB  - INTRODUCTION: Implementation of the Surviving Sepsis Campaign (SSC) guidelines
      has been associated with improved outcome in patients with severe sepsis.
      Resolution of lactate elevations or lactate clearance has also been shown to be
      associated with outcome. The purpose of the present study was to examine the
      compliance and effectiveness of the SSC resuscitation bundle with the addition of
      lactate clearance. METHODS: This was a prospective cohort study over 18 months in
      eight tertiary-care medical centers in Asia, enrolling adult patients meeting
      criteria for the SSC resuscitation bundle in the emergency department. Compliance
      and outcome results of a multi-disciplinary program to implement the Primary SSC
      Bundle with the addition of lactate clearance (Modified SSC Bundle) were
      examined. The implementation period was divided into quartiles, including
      baseline, education and four quality improvement phases. RESULTS: A total of 556
      patients were enrolled, with median (25th to 75th percentile) age 63 (50 to 74)
      years, lactate 4.1 (2.2 to 6.3) mmol/l, central venous pressure 10 (7 to 13)
      mmHg, mean arterial pressure (MAP) 70 (56 to 86) mmHg, and central venous oxygen
      saturation 77 (69 to 82)%. Completion of the Primary SSC Bundle over the six
      quartiles was 13.3, 26.9, 37.5, 45.9, 48.8, and 54.5%, respectively (P <0.01).
      The Modified SSC Bundle was completed in 10.2, 23.1, 31.7, 40.0, 42.5, and 43.6%
      patients, respectively (P <0.01). The ratio of the relative risk of death
      reduction for the Modified SSC Bundle compared with the Primary SSC Bundle was
      1.94 (95% confidence interval = 1.45 to 39.1). Logistic regression modeling
      showed that the bundle items of fluid bolus given, achieve MAP >65 mmHg by 6
      hours, and lactate clearance were independently associated with decreased
      mortality - having odds ratios (95% confidence intervals) 0.47 (0.23 to 0.96),
      0.20 (0.07 to 0.55), and 0.32 (0.19 to 0.55), respectively. CONCLUSIONS: The
      addition of lactate clearance to the SSC resuscitation bundle is associated with
      improved mortality. In our study patient population with optimized baseline
      central venous pressure and central venous oxygen saturation, the bundle items of
      fluid bolus administration, achieving MAP >65 mmHg, and lactate clearance were
      independent predictors of outcome.

PMID- 21951323
TI  - Living with life-saving technology - coping strategies in implantable
      cardioverter defibrillators recipients.
AB  - AIMS: To describe coping strategies and coping effectiveness in recipients with
      an implantable cardioverter defibrillator and to explore factors influencing
      coping. BACKGROUND: Implantable cardioverter defibrillators are documented as
      saving lives and are used to treat ventricular tachycardia and ventricular
      fibrillation. Despite the implantable cardioverter defibrillator not evidently
      interfering with everyday life, there is conflicting evidence regarding the
      psychosocial impact of an implantable cardioverter defibrillator implantation
      such as anxiety, depression, perceived control and quality of life and how these
      concerns may relate to coping. DESIGN: Cross-sectional multicentre design.
      METHODS: Individuals (n = 147, mean age 63 years, 121 men) who had lived with an
      implantable cardioverter defibrillator between 6-24 months completed the Jalowiec
      Coping Scale-60, Hospital Anxiety and Depression Scale, Control Attitude Scale
      and Quality of Life Index-Cardiac version. RESULTS: Implantable cardioverter
      defibrillators recipients seldom used coping strategies, and the coping
      strategies used were perceived as fairly helpful. Optimism was found to be the
      most frequently used (1.8 SD 0.68) and most effective (2.1 SD 0.48) coping
      strategy, and recipients perceived moderate control in life. Anxiety (beta = 3.5,
      p <= 0.001) and gender (beta = 12.3, p = 0.046) accounted for 26% of the variance
      in the total use of coping strategies, suggesting that the more symptoms of
      anxiety and being women the greater use of coping strategies. CONCLUSIONS: Most
      recipients with an implantable cardioverter defibrillator did not appraise daily
      concerns as stressors in need of coping and seem to have made a successful
      transition in getting on with their lives 6-24 months after implantation.
      Relevance to clinical practice.  Nurses working with recipients with an
      implantable cardioverter defibrillator should have a supportive communication so
      that positive outcomes such as decreased anxiety and increased perceived control
      and quality of life can be obtained. Through screening for anxiety at follow-up
      in the outpatient clinic, these recipients perceiving mental strain in their
      daily life can be identified.

PMID- 21951324
TI  - Quality assurance and improvement: the Pediatric Regional Anesthesia Network.
AB  - Quality assurance and improvement (QA/QI) is a critical activity in medicine. The
      use of large-scale collaborative databases is increasingly essential to obtain
      enough reports with which to establish standards of practice and define the
      incidence of complications and risk/benefit ratios for rare events. Such projects
      can enhance local QA/QI endeavors by enabling institutions to obtain benchmark
      data against which to compare their performance and can be used for prospective
      analyses of inter-institutional differences to determine 'best practice'. The
      pediatric regional anesthesia network (PRAN) is such a project. The first data
      cohort is currently being analyzed and offers insight into how such data can be
      used to detect trends in adverse events and improve care.

PMID- 21951325
TI  - Pulmonary function over 2 years in diabetic patients treated with prandial
      inhaled Technosphere Insulin or usual antidiabetes treatment: a randomized trial.
AB  - AIMS: Development of inhaled insulin has increased the need to understand its
      pulmonary safety. This study evaluated pulmonary function changes in diabetes
      patients receiving inhaled Technosphere Insulin (TI) or usual antidiabetes
      treatment (usual care). METHODS: This randomized, open-label study was conducted
      at 220 sites (25 July 2005 to 29 August 2008). Pulmonary function tests [forced
      expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC), total lung
      capacity (TLC) and lung diffusion capacity for carbon monoxide (DL(CO))] were
      prospectively followed over 2 years in patients with type 1 or type 2 diabetes
      receiving TI (n = 730) or usual care (n = 824), along with a cohort without
      diabetes not receiving any specific therapy (n = 145). RESULTS: Baseline
      demographics and pulmonary function were similar between diabetes treatment
      groups. Lung function declined from baseline in all groups. TI was non-inferior
      to usual care for mean change in FEV(1) from baseline to month 24 [mean (s.e.m.)
      0.037 (0.0119) l; 95% CI 0.014 to 0.060] using mixed-model repeated-measure with
      a pre-specified non-inferiority margin of 50 ml/year. After a greater initial
      decline at month 3 with TI, rate of change (slope) in FEV(1), FVC and DL(CO)
      (months 3-24) was not statistically different between treatment groups. TI was
      well tolerated; no serious safety concerns emerged. The most common respiratory
      event associated with TI was mild, transient cough, occurring within minutes of
      inhalation. CONCLUSIONS: Observed changes in lung function with TI were small,
      occurred early after therapy initiation, remained non-progressive over 2 years
      and were unlikely to be clinically meaningful.

PMID- 21951326
TI  - Overexpression of the immunoreceptor CD300f has a neuroprotective role in a model
      of acute brain injury.
AB  - It is well known that cell surface immune receptors play a critical role in
      regulating immune and inflammatory processes in the central nervous system (CNS).
      We have analyzed the function of cluster of differentiation (CD)300f
      immunoreceptor in a model of excitotoxic rat brain damage. First, to explore the
      presence of endogenous ligand(s) for this receptor we used a human CD300f-Ig
      soluble protein and confocal microscopy, showing specific staining mainly in CNS
      white matter and on the surface of oligodendrocytes and certain astrocytes. Next,
      we demonstrated in a model of in vivo rat brain excitotoxic damage that the
      overexpression of human CD300f induced a significant reduction in the lesion
      volume. To validate these results, we cloned the rat ortholog of CD300f protein
      (rCD300f). The overexpression of rCD300f receptor had a comparable
      neuroprotective effect after the acute brain injury and a similar CNS staining
      pattern when stained with the rCD300f-Ig soluble protein. Interestingly, when we
      analyzed the expression pattern of rCD300f in brain cells by quantitative
      polymerase chain reaction and immunohistochemistry, we detected the expression of
      CD300f as expected in microglial cells, but also in oligodendrocytes and neurons.
      These data suggest that the neuroprotective role of CD300f would be the result of
      a complex network of cell interactions.

PMID- 21951327
TI  - Anaemia among Egyptian Children between 2000 and 2005: trends and predictors.
AB  - Anaemia remains the most prevalent nutritional disorder among women and children
      in the Middle East and North Africa region. We examined anaemia trends using data
      from the Egyptian Demographic and Health Surveys. Between 2000 and 2005, the
      prevalence of anaemia (defined as haemoglobin concentrations <11 g dL(-1) )
      increased from 37.04% to over 52% among Egyptian children between 12 months and
      36 months of age. We examined the associations of these changes with food
      consumption, vitamin A administration, recent illness, immunization status, socio
      demographic factors and a child's anaemic status. Children under the age of 24
      months who had recently been sick and those who resided in Upper Egypt were
      significantly more likely to be anaemic. Despite significant improvements in
      water and sanitation facilities, maternal education and asset-based household
      wealth, there were marked declines in the consumption of nutritive foods and
      increases in the prevalence of childhood diarrhoea between 2000 and 2005. Placing
      these analyses in the broader context of Egyptian economic trends suggests that
      the nutritional basket consumed by Egyptian households between 2000 and 2005 may
      have shifted towards less nutritive foods with lower costs per calorie, probably
      in response to economic difficulties and increasing food prices. Shifts in
      dietary consumption, in conjunction with increases in diarrhoea, are likely
      contributing to the rapid increase in childhood anaemia in Egypt between 2000 and
      2005. National-level fortification efforts may be one way to combat rising levels
      of anaemia among Egyptian women and children.

PMID- 21951328
TI  - Efficacy of 1-mm minigrafts in treating vitiligo depends on patient age, disease
      site and vitiligo subtype.
AB  - Vitiligo vulgaris is a refractory skin disease. Treatment modalities include
      topical steroids, phototherapy, suction blister roof grafts and cellular grafting
      techniques. Adverse effects may occur, however, and some cases remain
      unresponsive to treatment. To evaluate the efficacy of small (1-mm) punch
      minigraft therapy in relation to patient age, disease site, disease duration and
      vitiligo subtype. We used a recently developed disposable 1.0-mm punch apparatus
      to perform minigraft therapy in 20 patients with either generalized (n = 4),
      segmental (n = 9) or limited (n = 7) vitiligo, and evaluated the area and rate of
      repigmentation in relation to patient age, disease site, disease duration and
      vitiligo subtype. The area of repigmentation was significantly greater in
      patients with segmental vitiligo (n = 9) than in those with generalized vitiligo
      (n = 4). Repigmentation covered a broader area and occurred more quickly in
      patients under 15 years of age than in those over 20 years of age (n = 9).
      Disease duration did not affect the repigmentation rate. The results of the
      present study suggest that 1-mm minigrafts are effective for treating patients
      with vitiligo. Better results occurred in patients under 15 years of age,
      patients with facial grafts, and patients with segmental and limited subtypes.

PMID- 21951329
TI  - Endothelial protein C receptor is required for tissue factor ternary complex
      signaling in the mouse.

PMID- 21951330
TI  - Prediction of sustained response to low-dose pegylated interferon alpha-2b plus
      ribavirin in patients with genotype 1b and high hepatitis C virus level using
      viral reduction within 2 weeks after therapy initiation.
AB  - AIM:   Continuation of pegylated interferon (PEG-IFN) plus ribavirin at the
      recommended dose is difficult in elderly patients and/or patients with cytopenia
      or complications. Whether the therapeutic efficacy of low-dose PEG-IFN plus
      ribavirin therapy could be predicted based on virological response within 2 weeks
      of therapy initiation was evaluated. METHODS:   A total of 106 patients with a
      high viral load of genotype-1b hepatitis C virus (HCV) underwent low-dose PEG-IFN
      plus ribavirin therapy. PEG-IFN alpha 2b (0.75 ug/kg per week) and ribavirin (600
      800 mg/day) were administered for 48 weeks. RESULTS:   Sustained virological
      response (SVR) was achieved in 37%, and treatment was discontinued in 9%. On
      univariate analysis of SVR-contributing factors, significant differences were
      noted in the white blood cell count, platelet count, fibrosis markers, and viral
      reduction within 2 weeks from therapy initiation. On multivariate analysis, the
      platelet count and the reduction in the HCV core antigen level at week 2 were
      independent factors. The positive predictive value (PPV) and the negative
      predictive value (NPV) for SVR based on a 1-log or greater HCV-RNA level
      reduction at week 2 were 65% and 90%, respectively, and those based on HCV core
      antigen level at week 2 were 64% and 97%, respectively. PPV and NPV based on a 2
      log or greater reduction of the RNA level were 86% and 67%, respectively, and
      those based on the core antigen level were 93% and 69%, respectively. CONCLUSION:
      Evaluation of viral reduction at week 2 after therapy initiation is useful for
      predicting SVR to low-dose PEG-IFN plus ribavirin therapy.

PMID- 21951331
TI  - Fat burners: nutrition supplements that increase fat metabolism.
AB  - The term 'fat burner' is used to describe nutrition supplements that are claimed
      to acutely increase fat metabolism or energy expenditure, impair fat absorption,
      increase weight loss, increase fat oxidation during exercise, or somehow cause
      long-term adaptations that promote fat metabolism. Often, these supplements
      contain a number of ingredients, each with its own proposed mechanism of action
      and it is often claimed that the combination of these substances will have
      additive effects. The list of supplements that are claimed to increase or improve
      fat metabolism is long; the most popular supplements include caffeine, carnitine,
      green tea, conjugated linoleic acid, forskolin, chromium, kelp and fucoxanthin.
      In this review the evidence for some of these supplements is briefly summarized.
      Based on the available literature, caffeine and green tea have data to back up
      its fat metabolism-enhancing properties. For many other supplements, although
      some show some promise, evidence is lacking. The list of supplements is industry
      driven and is likely to grow at a rate that is not matched by a similar increase
      in scientific underpinning.

PMID- 21951332
TI  - Factors regulating fat oxidation in human skeletal muscle.
AB  - In modern societies, oversupply of calories leads to obesity and chronic
      metabolic stress, which may lead to development of disease. Oversupply of
      calories is often associated with elevated plasma lipid concentrations and
      accumulation of lipids in skeletal muscle leading to decreased insulin
      sensitivity. Consequently, enhanced fat oxidation might be beneficial in
      counteracting lipid accumulation. Exercise is the most effective way to increase
      fat oxidation, because it increases metabolic rate. Lipid metabolism can also be
      altered by dietary manipulations. Thus, a fat rich diet leads to increased
      potential for fat oxidation by increasing the content of several of the proteins
      in the fat oxidative pathway. The regulation of both exercise and diet induced
      lipid oxidation will be discussed in this review.

PMID- 21951333
TI  - The search for compounds that stimulate thermogenesis in obesity management: from
      pharmaceuticals to functional food ingredients.
AB  - The concept of managing obesity through the stimulation of thermogenesis is
      currently a focus of considerable attention by the pharmaceutical, nutraceutical
      and functional food industries. This paper first reviews the landmark discoveries
      that have fuelled the search for thermogenic anti-obesity products that range
      from single-target drugs to multi-target functional foods. It subsequently
      analyses the thermogenic and fat-oxidizing potentials of a wide array of
      bioactive food ingredients which are categorized under methylxanthines,
      polyphenols, capsaicinoids/capsinoids, minerals, proteins/amino acids,
      carbohydrates/sugars and fats/fatty acids. The main outcome of this analysis is
      that the compounds or combination of compounds with thermogenic and fat-oxidizing
      potentials are those that possess both sympathomimetic stimulatory activity and
      acetyl-coA carboxylase inhibitory property, and are capable of targeting both
      skeletal muscle and brown adipose tissue. The thermogenic potentials of products
      so far tested in humans range from marginal to modest, i.e. 2-5% above daily
      energy expenditure. With an increasing number of bioactive food ingredients
      awaiting screening in humans, there is hope that this thermogenic potential could
      be safely increased to 10-15% above daily energy expenditure - which would have
      clinically significant impact on weight management, particularly in the
      prevention of obesity and in improving the long-term prognosis of post-slimming
      weight maintenance.

PMID- 21951335
TI  - The H(2)S test versus standard indicator bacteria tests for faecal contamination
      of water: systematic review and meta-analysis.
AB  - OBJECTIVES: To assess the diagnostic accuracy of the H(2)S test for
      microbiological contamination of domestic water across different settings, as a
      basis for providing guidance on its use. METHODS: We searched a range of
      bibliographic and 'grey' literature databases to identify studies that had
      processed domestic water samples using both the H(2)S test and recognized tests
      for thermotolerant coliforms or Escherichia coli. We screened 661 study abstracts
      and identified 51 relevant studies based on 13 853 water samples. For each
      relevant study, we recorded the level of correspondence between the H(2)S and
      recognized tests, microbial testing procedures, details of the samples processed
      and study quality indicators. We conducted a meta-analysis to investigate the
      impact of testing procedures, study quality and sample characteristics on the
      diagnostic accuracy of the H(2)S test. RESULTS: H(2)S test implementation varied
      between studies, and the test's diagnostic accuracy varied significantly and
      substantially between studies. Little of this variation was explained by testing
      procedures, study quality or the nature of the samples processed. CONCLUSIONS:
      Although in widespread use, our findings suggest that the diagnostic accuracy,
      particularly specificity, of the H(2)S test is variable. Optimal conditions for
      conducting the test remain unclear. As H(2)S test accuracy is low in a minority
      of these studies, we recommend that its performance be evaluated relative to
      standard methods, prior to its operational deployment in a new setting.

PMID- 21951336
TI  - Early cerebral infarction as a risk factor for poor outcome after aneurysmal
      subarachnoid haemorrhage.
AB  - BACKGROUND AND PURPOSE: After aneurysmal subarachnoid haemorrhage, severity of
      bleeding, and occurrence of rebleeding and cerebral infarcts are the main factors
      predicting outcome. We investigated predictive risk factors for both early and
      late cerebral infarcts, and whether time of appearance of infarct is associated
      with outcome. METHODS: Previous diseases as well as clinical, laboratory and
      radiological variables including serial CT scans were recorded for 173 patients
      admitted within 48 h after bleeding and with ruptured aneurysm occlusion by open
      surgery within 60 h. Factors predicting occurrence of cerebral infarct and poor
      outcome at 3 months according to the Glasgow Outcome Scale were tested using
      multiple logistic regression. RESULTS: Of several potential predictors, poor
      outcome was independently predicted by patient age, rebleeding, intraventricular
      haemorrhage, intracerebral haematoma, delayed cerebral ischaemia with fixed
      symptoms and early new ischaemic lesion on CT scan appearing on the 1st post
      operative morning (P<0.01 for each factor). After adjustment for confounding
      factors, occurrence of early infarct (odds ratio 12.5; 95% confidence interval
      3.2-48.7; P<0.01), both early and late infarct (6.6; 1.1-40.4; P<0.05), and late
      infarct only (2.4; 0.6-9.1) increased risk for poor outcome. Adjusted independent
      significant risk factors for early infarction were duration of artery occlusion
      during surgery (1.4/min; 1.1-1.7, P<0.01) and admission plasma glucose level (1.3
      per mM; 1.0-1.6, P<0.05) and for late infarction amount of subarachnoid blood
      (4.5; 1.3-14.9, P<0.05). CONCLUSION: Early infarction after surgical aneurysm
      occlusion seems to have different risk factors and worse prognosis than late
      infarct which is mostly associated with delayed cerebral ischaemia.

PMID- 21951338
TI  - Biofilm and penile prosthesis infections in the era of coated implants: a review.
AB  - INTRODUCTION: The numbers of inflatable penile prosthesis (IPP) implanted has
      increased yearly due to the large numbers of patients treated for prostate
      cancer, patients becoming refractory to the five phosphodiesterase inhibitors and
      Peyronie's disease. AIM: Prosthesis implantation can be associated with a variety
      of complications with device infection being the most dreaded one. MAIN OUTCOME
      MEASURES: An understanding of the pathogenesis of these infections is necessary
      to allow the surgeon to plan treatment. METHODS: Infection begins with
      colonization of planktonic bacteria in the implant space. Biofilm forms around
      the bacterial mass within 48 hours. Bacteria in biofilm have reduced growth
      rates, may change phenotypically, and develop resistance to drugs. Antibiotics
      and the body's macrophages will kill the planktonic bacteria released from the
      biofilm but never eliminate the infecting organisms. This review will delineate
      present thinking on infection prevention and biofilm's role in device infection.
      IPP infection before and after the coated implants will be characterized. Future
      ideas for prevention and treatment of infection will be explored. RESULTS: The
      coated implants have reduced the incidence of IPP infections. The bacteria that
      cause the majority of infections in the era of the coated implant seem to have
      changed from predominantly nosocomial coagulase-negative Staphylococcus to more
      virulent organisms. Device infection requires new paradigms of prevention and
      treatment strategy because the infecting bacteria are different and the patients
      are sicker. CONCLUSIONS: The problem of infection is considerably decreased with
      coated IPP, yet those infections that do occur are systemic in nature and seem to
      be caused by more aggressive organisms. These infections are not usually amenable
      to salvage because the virulence of the bacteria. Future research to prevent
      these infections must be directed to magnifying the effective dosage of
      antibiotics to penetrate the biofilm or eliminating the bacteria's ability to
      secrete the slime.

PMID- 21951339
TI  - Pemphigus vulgaris: accumulation of apoptotic cells in dermis and epidermis
      possibly relates to pathophysiology through TNF-alpha production by phagocytes.
AB  - Apoptotic cells are present in the epidermis of pemphigus vulgaris (PV) patients
      and their accumulation has been linked to chronic inflammatory disorders. TNF
      alpha is elevated in sera of PV patients and has only been detected in
      acantholytic and periacantholytic keratinocytes (KC), therefore another TNF-alpha
      source might exist. We analyzed, in lesional and perilesional skin of 5 active
      untreated PV patients, the presence of apoptotic cells, TNF-alpha and phagocytic
      infiltrate. In vitro, we analyzed whether phagocytosis of apoptotic KCs by
      monocytes causes TNF-alpha release. We found a significant increase of apoptotic
      cells in the epidermis and dermis of PV patients, by TUNEL, and activated caspase
      3. TNF-alpha was present in the skin of PV patients, especially in the dermis.
      Phagocytic CD14+ cells were increased, mostly in the dermis of PV patients. In
      vitro phagocytosis of apoptotic KCs by monocytes caused enhanced TNF-alpha
      production, which correlated with the number of apoptotic KCs in the co-culture.
      Thus, accumulation of apoptotic cells in PV could promote TNF-alpha production by
      monocytes, which could, in turn, cause further apoptosis, closing a vicious
      circle.

PMID- 21951340
TI  - Mitochondrial genome organization and divergence in hybridizing central European
      waterfrogs of the Pelophylax esculentus complex (Anura, Ranidae).
AB  - Natural transfer of mitochondrial DNA has occurred between three western
      Palaearctic waterfrog taxa: Pelophylax lessonae, Pelophylax ridibundus and their
      hybridogenetic hybrid, Pelophylax kl. esculentus. The transfer is asymmetric with
      most P. kl. esculentus and approximately one third of all central European P.
      ridibundus having mtDNA derived from P. lessonae (L-mtDNA). We obtained complete
      nucleotide sequences of multiple mitochondrial genomes (15,376-78 bp without
      control regions) from all 3 taxa, including a P. ridibundus frog with
      introgressed L-mtDNA. The gene content and organization of the mitogenomes
      correspond to those typical of neobatrachians. Divergence between the mtDNAs of
      P. lessonae and P. ridibundus is high with an uncorrected p-distance of 11.9%
      across the entire mitogenome. However, the rate of nucleotide substitution
      depends on the degree of functional constraint with up to 30-fold differences in
      levels of divergence. In general, mitochondrial genes encoding the translational
      machinery evolve very slowly, whereas genes encoding polypeptides of the electron
      transport system, especially the ND genes, evolve rapidly. Only 25 of 211-213
      observed amino acid replacements could be classified as radical and are therefore
      more likely to be exposed to selection. A disproportionately high number of amino
      acid substitutions has occurred in the ND4, ND4L and cytb genes of the P.
      lessonae lineage (including 36% of all radical changes). In contrast to the
      interspecific divergence, nucleotide polymorphism within L- and R-mtDNA is very
      low: L-mtDNA haplotypes differed on average by only 19 nucleotides, while there
      was no variation within two mtDNAs derived from P. ridibundus. This is an
      expected finding considering that we have sampled a post-glacial expansion area.
      Moreover, the introgressed L-mtDNA on a P. ridibundus background differed from
      other L-mtDNAs by only a few substitutions, indicative of a very recent
      introgression event. We discuss our findings in the context of natural selection
      acting on L-mtDNA and its potential significance in cytonuclear epistasis.

PMID- 21951337
TI  - Xenobiotic particle exposure and microvascular endpoints: a call to arms.
AB  - Xenobiotic particles can be considered in two genres: air pollution particulate
      matter and engineered nanoparticles. Particle exposures can occur in the greater
      environment, the workplace, and our homes. The majority of research in this field
      has, justifiably, focused on pulmonary reactions and outcomes. More recent
      investigations indicate that cardiovascular effects are capable of correlating
      with established mortality and morbidity epidemiological data following particle
      exposures. While the preliminary and general cardiovascular toxicology has been
      defined, the mechanisms behind these effects, specifically within the
      microcirculation, are largely unexplored. Therefore, the purpose of this review
      is several fold: first, a historical background on toxicological aspects of
      particle research is presented. Second, essential definitions, terminology, and
      techniques that may be unfamiliar to the microvascular scientist will be
      discussed. Third, the most current concepts and hypotheses driving cardiovascular
      research in this field will be reviewed. Lastly, potential future directions for
      the microvascular scientist will be suggested. Collectively speaking,
      microvascular research in the particle exposure field represents far more than a
      "niche." The immediate demand for basic, translational, and clinical studies is
      high and diverse. Microvascular scientists at all career stages are strongly
      encouraged to expand their research interests to include investigations
      associated with particle exposures.

PMID- 21951341
TI  - Tregs in infection and vaccinology: heroes or traitors?
AB  - The development of effective vaccines against life-threatening pathogens in human
      diseases represents one of the biggest challenges in biomedical science. Vaccines
      traditionally make use of the body's own immune armoury to combat pathogens. Yet,
      while our immune system is mostly effective in eliminating or controlling a
      diverse range of microorganisms, its responses are incomplete or somewhat limited
      in several other cases. How immune responses are restrained during certain
      infections has been a matter of debate for many years. The discovery of
      regulatory T cells (Tregs), an immune cell type that plays a central role in
      maintaining immune homeostasis and controlling appropriate immune responses, has
      shed light into many questions. Indeed, it has been proposed that while Tregs
      might be beneficial in preventing excessive tissue damage during infection, they
      might also favour pathogen persistence by restraining effector immune responses.
      In addition, Tregs are believed to limit immune responses upon vaccination.
      Different strategies have been pursued to circumvent Treg activity during
      immunization, but the lack of specific tools for their study has led sometimes to
      controversial conclusions. With the advent of novel mouse models that allow
      specific depletion and/or tracking of Treg populations in vivo, novel aspects of
      Treg biology during infection have been unravelled. In this review, we describe
      the new advances in understanding Treg biology during infection and evaluate Treg
      depletion as a novel adjuvant strategy for vaccination.

PMID- 21951342
TI  - The innate and adaptive immune response induced by alveolar macrophages exposed
      to ambient particulate matter.
AB  - Emerging epidemiological evidence suggests that exposure to particulate matter
      (PM) air pollution increases the risk of cardiovascular events but the exact
      mechanism by which PM has adverse effects is still unclear. Alveolar macrophages
      (AM) play a major role in clearing and processing inhaled PM. This comprehensive
      review of research findings on immunological interactions between AM and PM
      provides potential pathophysiological pathways that interconnect PM exposure with
      adverse cardiovascular effects. Coarse particles (10 MUm or less, PM(10)) induce
      innate immune responses via endotoxin-toll-like receptor (TLR) 4 pathway while
      fine (2.5 MUm or less, PM(2.5)) and ultrafine particles (0.1 MUm or less, UFP)
      induce via reactive oxygen species generation by transition metals and/or
      polyaromatic hydrocarbons. The innate immune responses are characterized by
      activation of transcription factors [nuclear factor (NF)-kappaB and activator
      protein-1] and the downstream proinflammatory cytokine [interleukin (IL)-1beta,
      IL-6, and tumor necrosis factor-alpha] production. In addition to the
      conventional opsonin-dependent phagocytosis by AM, PM can also be endocytosed by
      an opsonin-independent pathway via scavenger receptors. Activation of scavenger
      receptors negatively regulates the TLR4-NF-kappaB pathway. Internalized particles
      are subsequently subjected to adaptive immunity involving major
      histocompatibility complex class II (MHC II) expression, recruitment of
      costimulatory molecules, and the modulation of the T helper (Th) responses. AM
      show atypical antigen presenting cell maturation in which phagocytic activity
      decreases while both MHC II and costimulatory molecules remain unaltered. PM
      drives AM towards a Th1 profile but secondary responses in a Th1- or Th-2 up
      regulated milieu drive the response in favor of a Th2 profile.

PMID- 21951343
TI  - Molecular characterization of putative biocorroding microbiota with a novel niche
      detection of Epsilon- and Zetaproteobacteria in Pacific Ocean coastal seawaters.
AB  - Submerged metal surfaces in marine waters undergo rapid microbial colonization
      and biocorrosion, causing huge damage to marine engineering facilities and
      significant financial losses. In coastal areas, an accelerated and particularly
      severe form of biocorrosion termed accelerated low water corrosion (ALWC) is
      widespread globally. While identification of biocorroding microorganisms and the
      dynamics of their community structures is the key for understanding the processes
      and mechanisms leading to ALWC, neither one is presently understood. In this
      study, analysis of constructed clone libraries and qPCR assays targeting group
      specific 16S rRNA or functional marker genes were used to determine the identity
      and abundance of putative early carbon steel surface-colonizing and biocorroding
      microbes in coastal seawater. Diverse microbial groups including 10 bacterial
      phyla, archaea and algae were found to putatively participate in the surface
      colonizing process. Analysis of the community structure of carbon steel surface
      microbiota revealed a temporal succession leading to ALWC. By extending the
      current state of knowledge, our work demonstrates the global importance of
      Alphaproteobacteria (mainly Rhodobacterales), Gammaproteobacteria (mainly
      Alteromonadales and Oceanospirillales), Bacteroidetes (mainly Flavobacteriales)
      and microalgae as the pioneer and sustaining surface colonizers that contribute
      to initial formation and development of surface biofilms. We also discovered
      Epsilonproteobacteria and the recently described Zetaproteobacteria as putative
      corrosion-causing microorganisms during early steps of the ALWC process. Hence,
      our study reports that Zetaproteobacteria may be ubiquitous also in non
      hydrothermal coastal seawaters and that ALWC of submerged carbon steel surfaces
      in coastal waters may involve a highly diverse, complex and dynamic microbial
      consortium. Our finding that Epsilon- and Zetaproteobacteria may play pivotal
      roles in ALWC provides a new starting point for future investigation of the ALWC
      process and mechanism in marine environments. Further studies of Epsilon- and
      Zetaproteobacteria in particular may thus help with the design of effective
      corrosion prevention and control strategies.

PMID- 21951344
TI  - Oncology patients' perceptions of the good nurse: an explorative study on the
      psychometric properties of the Flemish adaptation of the Care-Q instrument.
AB  - AIMS AND OBJECTIVES: The aims of this study were to translate the Care-Q into
      Dutch, adapt it for use in oncological care settings in Flanders and explore its
      psychometric properties in oncology patients. BACKGROUND: The 'good nurse' is a
      difficult concept to measure. Patients' experiences are essential for
      understanding what characterises good nurses in the oncology setting. Although
      the Care-Q is one of the most widely used instruments to measure cancer patients'
      perceptions of good nurses, no translated, validated instrument has been
      developed for Flanders. DESIGN: A quantitative, descriptive, non-experimental
      research design was used. METHOD: We translated the Care-Q into Dutch, adapted it
      and assessed its face and content validity. Its psychometric properties were
      examined in 100 oncology patients. Internal consistency was assessed using
      Cronbach's alpha coefficient, and test-retest reliability was assessed using
      Wilcoxon matched pairs test and Spearman's rho coefficient. Factor structure was
      studied using explorative factor analysis derived from principal component
      analysis with varimax rotation, and the user-friendliness was examined using
      descriptive statistics. RESULTS: Several items from the original Care-Q were
      removed or adapted, and new items were added. The content validity index was
      0.83. Five reliable, consistent and meaningful subscales were identified that
      explained 49.7% of the total variance: good nurses are empathic (towards patients
      and family), professional, patient-centred, respectful and communicative.
      Cronbach's alpha was 0.92 for the whole instrument and 0.65-0.81 for the
      subscales. User-friendliness was deemed favourable. CONCLUSIONS: The Flemish
      adaptation of the Care-Q has favourable psychometric properties. It appears to be
      a useful instrument for studying cancer patients' perceptions of good nurses in
      Flanders. RELEVANCE TO CLINICAL PRACTICE: The Flemish adaptation of the Care-Q is
      useful for helping nurses to reflect critically on the care they offer and to
      adapt and improve care to the real needs and expectations of patients with
      cancer.

PMID- 21951345
TI  - Association of beta-cell function and insulin sensitivity with fasting and 2-h
      plasma glucose in a large Chinese population.
AB  - AIM: Our aim was to provide a quantitative analysis of the changes in the
      principal determinants of insulin sensitivity and secretion in relation to
      fasting plasma glucose (FPG) or 2-h plasma glucose (2h PG) in a Chinese
      population with a wide range of glucose tolerance. METHODS: A total of 5728
      adults spanning the entire range of glucose tolerance were included. Insulin
      sensitivity was measured by Matsuda insulin sensitivity index (ISI(M)) and
      homeostasis model assessment of 1/homeostasis model assessment of insulin
      resistance (HOMA-IR). beta-Cell function adjusted by insulin sensitivity was
      assessed from disposition index (DI) at early-phase DI(30) and total DI(120). The
      exponential curve was established as the best fit for the relationship between
      insulin sensitivity or beta-cell function and FPG or 2h PG. RESULTS: Relative to
      the trend classified as increasing 2h PG, hepatic insulin sensitivity and insulin
      secretion showed a decreasing trend to a substantial degree as FPG increased. A 1
      mmol/l increase in FPG and 2h PG concentration was associated with a -22 and -21%
      decline in ISI(M), -16 and -4% in 1/HOMA-IR, -38 and -35% in DI(30) and -36 and 
      26% in DI(120). The decay constant of ISI(M) and DI(30) in IFG or ISI(M), 1/HOMA
      IR, DI(30) and DI(120) in IGT was lower than that in normal glucose tolerance.
      Significant interactions between sex and glucose levels determining DI were
      found. CONCLUSIONS: We conclude that impairment of insulin sensitivity and
      insulin secretion contributes to both FPG or 2h PG hyperglycaemia in a Chinese
      population, but that the decline in insulin secretion is more pronounced with
      increasing fasting than 2h PG.

PMID- 21951346
TI  - Frequency and large T (LT) sequence of JC polyomavirus DNA in oligodendrocytes,
      astrocytes and granular cells in non-PML brain.
AB  - Progressive multifocal leukoencephalopathy (PML) and JCV granular cell
      neuronopathy occur secondary to JCV polyomavirus (JCV) infection of
      oligodendrocytes and cerebellar granular cell neurons (CGNs) during
      immunosuppression. Pure populations of astrocytes, oligodendrocytes, CGNs and
      microglia from frontal cortex and cerebellum of 17 non-PML patients (9
      immunocompetent; 8 immunosuppressed) were isolated by laser capture
      microdissection (LCM). JCV large T (LT) antigen DNA was detected by triple nested
      polymerase chain reaction (PCR). Sequence analysis was performed to assess LT
      gene variation. JCV DNA was detected in oligodendrocytes, astrocytes and CGNs of
      non-PML brains. The most common site for viral latency was cortical
      oligodendrocytes (65% of samples analyzed). Immunosuppressed patients were
      significantly more likely to harbor JCV DNA in CGN populations than
      immunocompetent patients (P = 0.01). Sequence analysis of the LT region revealed
      eight novel single nucleotide polymorphisms (SNPs) in four immunosuppressed
      patients. Of the eight novel SNPs detected, six were silent and two resulted in
      amino acid changes. JCV DNA is present within cells of the non-PML brain, known
      to be infected during PML and granular cell neuronopathy. This supports the
      argument for a brain only reservoir of JCV and supports the hypothesis that
      reactivation of latent brain JCV may be central to disease pathogenesis.

PMID- 21951348
TI  - Linear lichen planus pigmentosus of the forehead treated by neodymium:yttrium
      aluminum-garnet laser and topical tacrolimus.

PMID- 21951349
TI  - Mid-upper arm circumference and weight-for-height to identify high-risk
      malnourished under-five children.
AB  - The World Health Organization and UNICEF define non-oedematous severe acute
      malnutrition (SAM) either by a mid-upper arm circumference (MUAC) less than 115
      mm or by a weight-for-height z-score (WHZ) less than -3. The objective of this
      study was to assess whether there was any benefit to identify malnourished
      children with a high risk of death to combine these two diagnostic criteria. Data
      of a longitudinal study examining the relationship between anthropometry and
      mortality in rural Senegal and predating the development of community-based
      management of SAM were used for this study. First, the receiver operating
      characteristic (ROC) curves of MUAC and of WHZ to predict mortality were drawn,
      and then the points corresponding to WHZ less than -3 and/or MUAC less than 115
      mm were positioned in relation to these curves. MUAC had the highest ROC curve,
      which indicates that it identifies high-risk children better than WHZ. Both
      points representing WHZ less than -3 and/or MUAC less than 115 mm were below the
      MUAC ROC curve. It is concluded that to identify high-risk malnourished children,
      there is no benefit in using both WHZ less than -3 and/or MUAC less than 115 mm,
      and that using MUAC alone is preferable.

PMID- 21951350
TI  - Ensure your voice is heard in response to proposed changes in IRB rules.

PMID- 21951347
TI  - Islets transplanted in immunoisolation devices: a review of the progress and the
      challenges that remain.
AB  - The concept of using an immunoisolation device to facilitate the transplantation
      of islets without the need for immunosuppression has been around for more than 50
      yr. Significant progress has been made in developing suitable materials that
      satisfy the need for biocompatibility, durability, and permselectivity. However,
      the search is ongoing for a device that allows sufficient oxygen transfer while
      maintaining a barrier to immune cells and preventing rejection of the
      transplanted tissue. Separating the islets from the rich blood supply in the
      native pancreas takes its toll. The immunoisolated islets commonly suffer from
      hypoxia and necrosis, which in turn triggers a host immune response. Efforts have
      been made to improve the supply of nutrients by using proangiogenic factors to
      augment the development of a vascular supply in the transplant site, by using
      small islet cell aggregates to reduce the barrier to diffusion of oxygen, or by
      creating scaffolds that are in close proximity to a vascular network such as the
      omental blood supply. Even if these efforts are successful, the shortage of donor
      islet tissue available for transplantation remains a major problem. To this end,
      a search for a renewable source of insulin-producing cells is ongoing; whether
      these will come from adult or embryonic stem cells or xenogeneic sources remains
      to be seen. Herein we will review the above issues and chart the progress made
      with various immunoisolation devices in small and large animal models and the
      small number of clinical trials carried out to date.

PMID- 21951351
TI  - Relationships between physical activity and depressive symptoms among middle and
      older adolescents: a review of the research literature.
AB  - PURPOSE: The purpose of the review was to describe current knowledge regarding
      relationships between physical activity (PA) and depressive symptoms among
      adolescents. CONCLUSIONS: Inverse relationships were found between PA,
      particularly sports participation, and depressive symptoms. Limitations of the
      current research are discussed, including measurement issues. A major gap exists
      regarding research with youth at high risk for depressive symptoms and low levels
      of PA, including older, low-income, minority females. Future research should
      focus on high-risk populations such as youth attending alternative high schools.
      PRACTICE IMPLICATIONS: Nurses should consider promoting PA among middle and older
      adolescents as a way to prevent depressive symptoms and consider integrating PA
      into care plans for those experiencing depressive symptoms.

PMID- 21951352
TI  - Forensic nurses' experiences of receiving child abuse disclosures.
AB  - PURPOSE: A child's self-disclosure of abuse is a critical component in initiating
      intervention to stop abuse and decrease the likelihood of long-term negative
      outcomes. This study described the context in which child abuse victims disclosed
      to forensic nurses. DESIGN AND METHODS: Thirty interviews were conducted at the
      International Forensic Nurses Scientific Assembly 2007 and then analyzed using
      narrative inquiry methodology. RESULTS: Five themes emerged: child-friendly
      environment, building rapport, engaged listening, believing unconditionally, and
      the potential for false disclosures. PRACTICE IMPLICATIONS:   Nurses can provide
      an environment that allows a child the perception of limitless time to share
      their unique stories.

PMID- 21951353
TI  - Outcomes of nutrition knowledge and healthy food choices in 5- to 6-year-old
      children who received a nutrition intervention based on Piaget's theory.
AB  - PURPOSE: To develop nutrition education for preschool children based on Piaget's
      theory and to examine the effects of this education on children's nutritional
      knowledge, nutritional behaviors, and anthropometric measurements. DESIGN AND
      METHODS: Pre- and postexperimental design. In experimental schools nutrition
      education was given. Children's nutritional knowledge, food consumption
      frequencies, and anthropometric measurements were evaluated. RESULTS: The
      experimental group's nutritional knowledge scores increased and the group's food
      preferences positively changed. No significant difference was observed between
      the experimental and control groups' anthropometric measurements. PRACTICE
      IMPLICATIONS: The nutrition education program used in this study may guide nurses
      in preparing education for preschoolers. The participation of families is
      recommended in their children's nutrition program.

PMID- 21951355
TI  - How effective is a short-term educational and support intervention for families
      of an adolescent with type 1 diabetes?
AB  - PURPOSE: To study adaptation and coping strategies of parents who had adolescents
      with diabetes and the effect of a short-term educational and support
      intervention. DESIGN AND METHOD: A quasi-experimental design was used in the
      study on 23 families of adolescents with diabetes. RESULTS: A significant
      difference was found between parents' coping patterns before the intervention.
      Fathers were, however, found to rate their coping patterns significantly more
      helpful after the intervention than before. The mothers demonstrated,
      nevertheless, a significantly greater use of all the coping patterns. PRACTICE
      IMPLICATIONS: Educational and support intervention is helpful for parents of
      adolescents with diabetes.

PMID- 21951354
TI  - The pediatric PRO-SELF(c): pain control program: an effective educational program
      for parents caring for children at home following tonsillectomy.
AB  - PURPOSE: The purpose of this paper was to provide a description of the components
      of the PEDIATRIC PRO-SELF(c): Pain Control Program. DESIGN AND METHODS: The
      Program, adapted from studies of this intervention in adults with cancer pain,
      was tested in two randomized clinical trials of acute pain management in
      pediatrics. RESULTS: Key strategies most effective for parents in the pediatric
      ambulatory surgery setting included use of an educational booklet and timer to
      facilitate adherence to the prescribed analgesic regimen, as well as interactive
      nursing support. PRACTICE IMPLICATIONS:   The PEDIATRIC PRO-SELF(c): Pain Control
      Program can be used with parents caring for children at home following
      tonsillectomy.

PMID- 21951356
TI  - Care coordination for children with complex care needs significantly reduces
      hospital utilization.
AB  - PURPOSE: The purpose was to evaluate an ambulatory care coordination program for
      children with complex care needs. DESIGN AND METHODS: A pre- and postcohort
      evaluation design was implemented to analyze the impact on hospital utilization.
      RESULTS: Results included a decrease in emergency department presentations (15%,
      p < .001), hospital admissions (9%, p < .019), and hospital bed days (43%, p <
      .001). Economic analysis indicated a cost savings of $A 1.9 million per annum.
      PRACTICE IMPLICATIONS: Hospital utilization is significantly reduced for children
      with complex care needs through 24/7 care coordination.

PMID- 21951357
TI  - Caring for children following radiation disaster.

PMID- 21951358
TI  - Practical issues of physiologic measurement for clinical research with children:
      part II: establishing feasibility.

PMID- 21951359
TI  - Hepatic steatosis in chronic hepatitis C patients infected with genotype 2 is
      associated with insulin resistance, hepatic fibrosis and affects cumulative
      positivity of serum hepatitis C virus RNA in peginterferon and ribavirin
      combination therapy.
AB  - AIM:   Hepatic steatosis is one of the factors limiting the virological response
      to interferon-based antiviral therapy for chronic hepatitis C (CH-C) patients
      infected with genotype 1, while contradictory results have been reported for
      genotype 2. We aimed to clarify the effect of hepatic steatosis on therapeutic
      outcome and cumulative positivity of serum HCV RNA in CH-C patients infected with
      genotype 2 treated by peginterferon (PEG-IFN)alpha2b and ribavirin (RBV)
      combination therapy. METHODS:   A total of 74 treatment-naive non-cirrhotic CH-C
      patients infected with genotype 2 who received PEG-IFNalpha2b and RBV according
      to the standard regimen were divided into hepatic steatosis 0-10% and >10%
      groups. The clinical backgrounds, sustained virological response (SVR) rates and
      cumulative positivity of serum HCV RNA were compared between the two groups.
      RESULTS:   Among the 74 patients, 61 (82.4%) had hepatic steatosis 0-10% and 13
      (17.6%) had hepatic steatosis >10%. Scores of homeostasis model assessment
      insulin resistance and hepatic fibrosis were higher in patients with hepatic
      steatosis >10% than hepatic steatosis 0-10% (P = 0.040 and 0.042, respectively).
      Non-SVR was more frequent in patients with hepatic steatosis >10% than hepatic
      steatosis 0-10% (P = 0.003). Cumulative positivity of serum HCV RNA was
      significantly higher in patients with hepatic steatosis >10% than hepatic
      steatosis 0-10% (P = 0.004). CONCLUSIONS:   In CH-C patients infected with
      genotype 2 treated by PEG-IFNalpha2b and RBV combination therapy, hepatic
      steatosis >10% was associated with increased insulin resistance, advanced hepatic
      fibrosis and higher cumulative positivity of serum HCV RNA, which lead to a
      higher risk of non-SVR.

PMID- 21951360
TI  - A systematic review and meta-analysis of the effect of aerobic vs. resistance
      exercise training on visceral fat.
AB  - It is increasingly recognized that the location of excess adiposity, particularly
      increased deposition of visceral adipose tissue (VAT), is important when
      determining the adverse health effects of overweight and obesity. Exercise
      therapy is an integral component of obesity management, but the most potent
      exercise prescription for VAT benefit is unclear. We aimed to evaluate the
      independent and synergistic effects of aerobic exercise (AEx) and progressive
      resistance training (PRT) and to directly compare the efficacy of AEx and PRT for
      beneficial VAT modulation. A systematic review and meta-analysis was performed to
      assess the efficacy of exercise interventions on VAT content/volume in overweight
      and obese adults. Relevant databases were searched to November 2010. Included
      studies were randomized controlled designs in which AEx or PRT in isolation or
      combination were employed for 4 weeks or more in adult humans, where computed
      tomography (CT) or magnetic resonance imaging (MRI) was used for quantification
      of VAT pre- and post-intervention. Of the 12196 studies from the initial search,
      35 were included. After removal of outliers, there was a significant pooled
      effect size (ES) for the comparison between AEx therapy and control (-0.33, 95%
      CI: -0.52 to -0.14; P < 0.01) but not for the comparison between PRT therapy and
      control (0.09, 95% CI: -0.17 to -0.36; P = 0.49). Of the available nine studies
      which directly compared AEx with PRT, the pooled ES did not reach statistical
      significance (ES = 0.23, 95% CI: -0.02 to 0.50; P = 0.07 favouring AEx). The
      pooled ES did not reach statistical significance for interventions that combined
      AEx and PRT therapy vs. control (-0.28, 95% CI: -0.69 to 0.14; P = 0.19), for
      which only seven studies were available. These data suggest that aerobic exercise
      is central for exercise programmes aimed at reducing VAT, and that aerobic
      exercise below current recommendations for overweight/obesity management may be
      sufficient for beneficial VAT modification. Further investigation is needed
      regarding the efficacy and feasibility of multi-modal training as a means of
      reducing VAT.

PMID- 21951361
TI  - Classical conditioning of sexual response in women: a replication study.
AB  - INTRODUCTION: According to incentive motivation models, sexual stimuli play a
      crucial role in eliciting sexual arousal, desire, and behavior. Therefore, it
      seems highly valuable to investigate the process through which stimuli acquire
      motivational value. Although many theories of human sexual behavior assume that
      sexual stimuli obtain arousing properties through classical conditioning,
      systematic research on classical conditioning of sexual responses in humans is
      scarce. Recently, however, our research group observed conditioned genital
      responses in women using a differential conditioning procedure and genital
      vibrostimulation as unconditional stimulus (US). AIM: The aim of the present
      experiment was to perform an extended replication of this previous study to test
      the efficacy of our conditioning paradigm. METHODS: A differential conditioning
      experiment was conducted in 32 sexually functional women. Neutral pictures served
      as conditional stimuli (CSs) and genital vibrostimulation as US. Only one CS (the
      CS+) was followed by the US during the acquisition phase. Conditioned responses
      were assessed during the extinction phase. MAIN OUTCOME MEASURES: Vaginal pulse
      amplitude (VPA) and skin conductance level were assessed, and ratings of
      affective value and sexual arousal were obtained. RESULTS: As expected, during
      the extinction phase, VPA was higher in response to the CS+ than to the CS-.
      Also, the CS+ tended to be evaluated as more positive and as more sexually
      arousing than the CS-. In addition, the magnitude of conditioned subjective
      affect was related to scores on the Sexual Inhibition?Sexual Excitation Scales.
      Skin conductance levels showed no conditioning effect. CONCLUSIONS: Genital and
      subjective sexual responses were successfully modulated by the differential
      conditioning paradigm. This replication of our previous study confirms the
      effectiveness of our conditioning procedure and indicates that it may provide a
      fruitful paradigm for further research on associative sexual reward learning in
      humans.

PMID- 21951362
TI  - Pigmented Bowen's disease of the digit successfully treated with imiquimod 5%
      cream.

PMID- 21951363
TI  - Synthesis, in vitro antitubercular activity and 3D-QSAR of novel quinoxaline
      derivatives.
AB  - Twenty new quinoxalines bearing azetidinone and thiazolidinone groups were
      synthesized by cyclocondensation of Schiff bases of quinoxaline-2, 3-dione and
      were characterized with several analytical tools. They were tested against
      Mycobacterium tuberculosis H37Rv at a concentration of 10 MUg/mL by Microplate
      Alamar Blue Assay method. Quinoxaline derivatives with 2-chloro, dimethylamino
      and nitro substitutions exhibited in vitro activity, comparable to that of the
      drug, isoniazid. Three-dimensional quantitative structure-activity relationship
      studies indicated that electrostatic and steric field descriptors could explain
      the observed activity. The developed model fits the data well and has good
      predictive capability (r2 = 0.81, q2 = 0.71, F = 27.06, r2 _pred = 0.84, r2(m) =
      0.84, r2 BS = 0.80). Electronegative groups play an important role in the
      antitubercular activity.

PMID- 21951364
TI  - Agomelatine: protecting the CNS from the effects of stress.

PMID- 21951365
TI  - Hypothermia reduces brain edema, spontaneous recurrent seizure attack, and
      learning memory deficits in the kainic acid treated rats.
AB  - AIMS: It is unknown whether hypothermia can disrupt the progress of
      epileptogenesis. The present study aimed to determine the effect of hypothermia
      on brain edema and epileptogenesis and to establish whether brain edema is
      associated with epileptogenesis after severe status epilepticus (SE).
      METHODOLOGY: Rats were injected with a single dose of Kainic acid (KA) to produce
      either chronic epileptic rats (rats with spontaneous recurrent seizure, SRS) or
      rats without spontaneous recurrent seizure (no-SRS rats). A second KA injection
      was used to induce SE in SRS rats and in no-SRS rats. The number of SRS was
      counted and the brain edema induced by SE was assessed by brain water content
      measurement. The cognitive function was assessed by the radial-arm maze (RAM)
      test. RESULTS: A second KA injection resulted in brain edema that was more severe
      in SRS rats than in no-SRS rats. After second injection of KA, hypothermia
      treatment attenuated the KA induced brain edema and reduced the SRS attack in SRS
      rats. Additionally cognitive function was better in hypothermia-treated SRS rats
      than in nomothermia treated SRS rats 1 month after the second KA injection.
      CONCLUSIONS: Hypothermia treatment immediately after SE not only exhibited
      protective effects against the chronic spontaneous recurrent convulsant seizures
      but also improved cognitive function. These antiepileptogenic properties of
      hypothermia may be related to its attenuating effect on brain edema induced by
      SE. They therefore suggest that brain edema may be involved in the progress of
      epileptogenesis.

PMID- 21951366
TI  - Deficiency of NG2+ cells contributes to the susceptibility of stroke-prone
      spontaneously hypertensive rats.
AB  - AIMS: The purpose of this study is to investigate whether the NG2(+) cells, a
      class of oligodendrocyte progenitor cells, is involved in the pathophysiology of
      stroke in stroke-prone spontaneously hypertensive rat (SHR-SP). METHODS: SHR-SP,
      SHR, Wistar-Kyoto rats (WKY), and C57BJ/6 mice were used. Immunohistochemistry
      was conducted to evaluate the number of NG2(+) cells in frozen brain sections.
      Demyelination was evaluated by Sudan black staining and serum level of myelin
      basic protein. Middle cerebral artery occlusion (MCAO) was performed to prepare
      experimental stroke model. RESULTS: The number of NG2(+) cells was significantly
      decreased in infarct core and increased in penumbra in WKY rats after MCAO. In
      brain sections of 6-month-old SHR-SP, the number of NG2(+) cells was
      significantly (P < 0.01) less than that in age-matched SHR and WKY rats. However,
      this phenomenon was not observed in 3-month-old rats. Demyelination was found in
      6-month-old SHR-SP but not in 3-month-old SHR-SP. Pharmacological treatment of
      cuprizone in mice induced demyelination and enlargement of cerebral infarction
      after MCAO. CONCLUSION: The decline of NG2(+) cells may cause demyelination and
      contribute to the susceptibility of SHR-SP to ischemic brain injury.

PMID- 21951367
TI  - Possible role of glia in cognitive impairment in schizophrenia.
AB  - Cognitive impairment is a core disorder of the schizophrenia syndrome. Based on
      glial-neuronal interactions, a pathophysiological model is proposed that could be
      explanatory for cognitive impairment in schizophrenia. The model consists of
      three main hypotheses concerning the pathophysiology in tripartite synapses,
      oligodendrocyte-axonic interactions, and in the glial networks (astrocytic
      syncytium). In tripartite synapses nonfunctional astrocytic receptors may cause
      an unconstrained synaptic information flux, since they cannot be occupied by
      neurotransmitters (NTs). Therefore, a generalization of information processing
      may occur in the brain causing hallucinations, delusions, and thought disorder.
      If the oligodendrocyte-axonic system decomposes, the brain is unable to process
      information in qualitative domains or categories. This may lead to severe
      incoherence phenomena such as thought disorder. Supposing that in the astrocytic
      syncytium gap junctions (g.js) normally form plaques functioning as memory
      devices, loss of function of g.j. may also cause cognitive impairment, since the
      syncytium decomposes and g.j. plaques cannot be generated. These hypotheses are
      experimentally testable. Finally, the problem of treatment of patients with
      schizophrenia is discussed, in case the presented model of schizophrenia might be
      verified.

PMID- 21951368
TI  - Effects of cholinesterase inhibitors in Parkinson's disease dementia: a review of
      clinical data.
AB  - AIMS: Cognitive impairment and dementia are common features of Parkinson's
      disease (PD). Patients with Parkinson's disease dementia (PDD) often have
      significant cholinergic defects, which may be treated with cholinesterase
      inhibitors (ChEIs). The objective of this review was to consider available
      efficacy, tolerability, and safety data from studies of ChEIs in PDD.
      DISCUSSIONS: A literature search resulted in the identification of 20 relevant
      publications. Of these, the treatment of PD patients with rivastigmine,
      donepezil, or galantamine was the focus of six, eleven, and two studies
      respectively, while one study reported use of both tacrine and donepezil. The
      majority of studies were small (<40 patients), with the exception of two large
      randomized controlled trials (RCTs) that are the main focus of this review. In
      the smaller studies, treatment benefits were reported on a range of outcome
      measures, though results were extremely variable. While the full results of a
      large RCT of donepezil in patients with PDD are not yet available, significant
      treatment differences were reported on the CIBIC-plus at the highest treatment
      dose. A trend toward improvement was also observed in treated patients on the
      ADAS-cog. The second large RCT found significant improvements in rivastigmine
      treated patients compared with placebo on both the ADAS-cog (P < 0.001) and the
      ADCS-CGIC (P < 0.007), as well as on all secondary efficacy outcomes.
      Consequently, rivastigmine is now widely approved for the symptomatic treatment
      of mild to moderate PDD. CONCLUSIONS: Taken together, these studies suggest that
      ChEIs are efficacious in the treatment of PDD.

PMID- 21951369
TI  - Acute drug administration in epilepsy: a review.
AB  - AIMS: To review acute administration of drugs in epilepsy for indications other
      than status epilepticus. DISCUSSION: This review looks into the application of
      acute drug administration (ADA) against febrile and prolonged nonfebrile seizures
      in children, seizure clustering (habitual or at drug withdrawal), catamenial
      epilepsy, response to seizure "warnings", and prophylaxis of seizures at
      perceived increased risk (reflex epilepsies, long-distance travel, lifestyle, and
      social occasions). The drugs most commonly used for ADA are the benzodiazepines
      diazepam (oral or rectal), clobazam and buccal or nasal midazolam, and lorazepam.
      Others include valproic acid, nitrazepam, acetazolamide, chloral hydrate,
      pyridoxine, and antipyretics. CONCLUSIONS: The best evidence for the efficacy of
      ADA exists in febrile and nonfebrile childhood seizures, whereas the evidence in
      catamenial epilepsy is weak. Prevention of clusters is a well-proven principle
      but its application has been little studied. Prevention of imminent seizures
      predicted by well-established triggers, defined risk factors, or premonitory
      minor seizure activity seems to be at the same time the most intelligent and the
      least investigated application of ADA and would deserve to be better studied.

PMID- 21951370
TI  - The use of antidepressants for headache prophylaxis.
AB  - The focus of this review is on the efficacy of antidepressants as preventive
      treatments for migraine and chronic tension-type headache (TTH). Pharmacologic
      prophylaxis may be indicated for patients with frequent headaches, who respond
      insufficiently to acute therapies, or for whom medication overuse is a concern.
      The well-documented efficacy of the tricyclic antidepressant amitriptyline, both
      for migraine and chronic TTH, has been followed by widespread use of other
      antidepressants for headache prophylaxis. Although antidepressants in general
      share comparable efficacy for the treatment of depressive disorders, their
      efficacy as headache preventives varies widely. Evidence supporting use of the
      selective serotonin reuptake inhibitors as headache preventives is poor; their
      use should be reserved for treating comorbid depression in a patient who also has
      a headache disorder. Small randomized trials of venlafaxine indicate preliminary
      efficacy both for migraine and tension-type headache. Evidence for other
      antidepressants is lacking. Although antidepressants are often prescribed to
      headache patients under the assumption that the prescribed agent also will be
      effective in reducing symptoms of comorbid depression, the majority of studies
      have failed to find a strong relationship between depression symptoms and
      headache improvement. Suggestions for future research are discussed.

PMID- 21951371
TI  - Neuropsychiatric adverse effects of centrally acting antiobesity drugs.
AB  - INTRODUCTION: Central neurochemical systems including the monoamine, opioid, and
      cannabinoid systems have been promising targets for antiobesity drugs that modify
      behavioral components of obesity. In addition to modulating eating behavior,
      centrally acting antiobesity drugs are also likely to alter emotional behavior
      and cognitive function due to the high expression of receptors for the
      neurochemical systems targeted by these drugs within the fronto-striatal and
      limbic circuitry. METHODS: This paper reviewed the neuropsychiatric adverse
      effects of past and current antiobesity drugs, with a central mechanism of
      action, linking the adverse effects to their underlying neural substrates and
      neurochemistry. RESULTS: Antiobesity drugs were found to have varying
      neuropsychiatric adverse event profiles. Insomnia was the most common adverse
      effect with drugs targeting monoamine systems (sibutramine, bupropion and
      tesofensine). These drugs had some positive effects on mood and anxiety and may
      have added therapeutic benefits in obese patients with comorbid depression and
      anxiety symptoms. Sedation and tiredness were the most common adverse effects
      reported with drugs targeting the m-opioid receptors (i.e., naltrexone) and
      combination therapies targeting the opioid and monoamine systems (i.e.,
      ContraveTM). Cognitive impairments were most frequently associated with the
      antiepileptic drugs, topiramate and zonisamide, consistent with their sedative
      properties. Drugs targeting the cannabinoid system (rimonabant and taranabant)
      were consistently associated with symptoms of anxiety and depression, including
      reports of suicidal ideation. Similar adverse events have also been noted for the
      D1/D5 antagonist ecopipam. CONCLUSION: These findings highlight the need to
      assess neuropsychiatric adverse events comprehensively using sensitive and
      validated methods early in the clinical development of candidate antiobesity
      drugs with a central mechanism of action.

PMID- 21951372
TI  - The genetics of white matter lesions.
AB  - White matter lesions (WMLs), commonly seen as hyperintensities on T2-weighted MRI
      scans of healthy elderly individuals, are considered to be related to small
      vessel disease in the brain, and are often associated with subtle cognitive and
      functional impairments. WMLs also show a strong correlation with a wide range of
      neurodegenerative and neuropsychiatric disorders. Although a number of vascular
      risk factors for WMLs have been identified, genetic factors are also important
      with twin and family studies reporting high heritability. Mutations in several
      genes have been described that lead to monogenic disorders manifesting WMLs, such
      as Fabry disease and CADASIL. Because most individuals with WMLs do not have
      Mendelian disorders, most of the focus has been on single nucleotide
      polymorphisms as genetic risk markers for WMLs, either directly or through their
      interactions with other genes or medical risk factors. Candidate genes examined
      to date include those involved in cholesterol regulation and atherosclerosis,
      hypertension, neuronal repair, homocysteine levels, and oxidative stress
      pathways. In addition, although there have been a few genome-wide linkage
      studies, only one genome-wide association study has been performed. The majority
      of the genetic findings need independent replication, and studies need to be
      extended to other candidate genes. Collaborative efforts to examine genome-wide
      associations in large samples of both sexes of a broad age range using
      longitudinal studies are necessary. The identification of individuals genetically
      at risk of developing white matter lesions will have important implications for
      recognizing the etiology of WMLs and thereby developing clinical intervention
      strategies for their prevention.

PMID- 21951373
TI  - From hypertension to stroke: mechanisms and potential prevention strategies.
AB  - Stroke is a major cause of disability and death worldwide. Prevention aimed at
      risk factors of stroke is the most effective strategy to curb the stroke
      pandemic. Hypertension is one of the most important risk factors for stroke.
      Despite the substantial evidence of the benefits of lowering blood pressure,
      conventional treatment does not normalize the burden of major cardiovascular
      events in patients with hypertension. Fully understanding the factors involved in
      the hypertension-induced stroke helps to develop new strategies for stroke
      prevention. Antihypertensive therapies selected should have positive blood
      pressure-independent effects on stroke risk. This review summarizes the factors
      involved in the hypertension-induced stroke, such as oxidative stress,
      inflammation, and arterial baroreflex dysfunction, and potential strategies for
      its prevention, therefore, provides clues for clinicians.

PMID- 21951374
TI  - Effect of the breast health program based on health belief model on breast health
      perception and screening behaviors.

PMID- 21951375
TI  - No increase in headache after previous intracranial infections: a historical
      cohort study (HUNT).
AB  - BACKGROUND AND PURPOSE: Despite the absence of robust scientific evidence, it is
      today generally accepted that the acute headache typical for intracranial
      infections can develop into permanent headache complaints. This widespread
      concept was explored in the first, large, longitudinal, population-based study.
      METHODS: Data on confirmed exposure to intracranial infections amongst all adult
      inhabitants in a geographical area during a 20-year period were assembled from
      hospital records. Surviving individuals were later invited to the third Nord
      Trondelag Health Survey (HUNT 3), where 39,690 (42%) of 94,194 invited
      inhabitants aged >=20 years responded to a validated headache questionnaire.
      Using logistic regression, the 1-year prevalence of headache and its subtypes
      according to the diagnostic criteria of the International Headache Society was
      assessed and compared between those with and without previous confirmed
      intracranial infection. Age and sex were used as covariates. RESULTS: Overall, 43
      participants were identified with earlier intracranial infection, whereof three
      had more than one infection: bacterial meningitis (n=19), lymphocytic meningitis
      (n=18), encephalitis (n=9), and brain abscess (n=1).The mean interval from
      infection to participation in HUNT 3 was 11.2 (range 1.5-19.7) years. There was
      no significant increase in the prevalence of headache (OR 1.10, 95% CI 0.58
      2.07), its subtypes (migraine, or tension-type headache), or chronic daily
      headache (OR 1.85, 95% CI 0.45-7.68) amongst participants with previous
      intracranial infection compared with the surrounding population. CONCLUSIONS:
      This study challenges the existence of chronic post-bacterial meningitis headache
      and does not indicate the presence of other long-term headaches induced by
      intracranial infection.

PMID- 21951376
TI  - Clinical predictors and outcome of hypoxaemia among under-five diarrhoeal
      children with or without pneumonia in an urban hospital, Dhaka, Bangladesh.
AB  - OBJECTIVE: To explore the predictors and outcome of hypoxaemia in children under
      5 years of age who were hospitalized for the management of diarrhoea in Dhaka,
      where comorbidities are common. METHODS: In a prospective cohort study, we
      enrolled all children <5 years of age admitted to the special care ward (SCW) of
      the Dhaka Hospital of ICDDR,B from September to December 2007. Those who
      presented with hypoxaemia (SpO(2) < 90%) constituted the study group, and those
      without hypoxaemia formed the comparison group. RESULTS: A total of 258 children
      were enrolled, all had diarrhoea. Of the total, 198 (77%) had pneumonia and 106
      (41%) had severe malnutrition (<-3 Z-score of weight for age of the median of the
      National Centre for Health Statistics), 119 (46%) had hypoxaemia and 138 children
      did not have hypoxaemia at the time of admission. Children with hypoxaemia had a
      higher probability of a fatal outcome (21%vs. 4%; P < 0.001). Using logistic
      regression analysis, the independent predictors of hypoxaemia at the time of
      presentation were lower chest wall indrawing [OR 6.91, 95% confidence intervals
      (CI) 3.66-13.08, P < 0.001], nasal flaring (OR 3.22, 95% CI 1.45-7.17, P = 0.004)
      and severe sepsis (OR 4.48, 95% CI 1.62-12.42, P = 0.004). CONCLUSION: In this
      seriously ill population of children with diarrhoea and comorbidities, hypoxaemia
      was associated with high case-fatality rates. Independent clinical predictors of
      hypoxaemia in this population, identifiable at the time of admission, were lower
      chest wall indrawing, nasal flaring and the clinical syndrome of severe sepsis.

PMID- 21951378
TI  - Challenges in handling elder abuse in community care. An exploratory study among
      nurses and care coordinators in Norway and Australia.
AB  - AIM AND OBJECTIVE: The aim of this study was to explore how nurses and care
      coordinators in community care in Norway and Australia experienced and handled
      cases of abused older clients, including the support they received in clinical
      interventions. BACKGROUND: Norway and Australia base their approaches to elder
      abuse problems on similar philosophies. The Australian Government, however, has
      taken a more active position on this issue by focusing on structures and policies
      that might influence professionals' handling of abuse cases. The organisation and
      funding of community care services in the two countries are different, although
      common concerns are client-centeredness, equal access to services and enabling
      the client to live at home as long as possible. DESIGN: Explorative design with a
      qualitative hermeneutic approach. METHOD: Twenty participants, nurses, auxiliary
      nurses and care workers in Norway and Australia, were recruited by purposeful
      sampling. They participated in in-depth interviews. RESULTS: The similarity of
      the information given in the two countries was striking. The interventions
      differed based on the type and seriousness of the abuse and the client's
      cognitive capacity. Financial abuse was a more prominent issue in Australia than
      in Norway. The handling of neglect cases in both countries followed much the same
      pathway and the intervention usually involved long-lasting processes. The
      managers' support and the elder protective services were of great importance to
      the nurses. CONCLUSIONS: Community care agencies in both countries struggle with
      similar problems in handling cases of abuse. The participants' concerns were
      securing and supporting the older victim by individualising the intervention.
      RELEVANCE TO CLINICAL PRACTICE: Community care agencies in both countries need to
      be aware of the huge impact of the managers' involvement and the services'
      responsibility and capacity to support professionals in the handling of elder
      abuse.

PMID- 21951377
TI  - Evaluation of adjuvant chemoradiation therapy for ampullary adenocarcinoma: the
      Johns Hopkins Hospital-Mayo Clinic collaborative study.
AB  - BACKGROUND: The role of adjuvant chemoradiation therapy for ampullary carcinoma
      is unknown. Previous literature suggests that certain populations with high risk
      factors for recurrence may benefit from adjuvant chemoradiation. We combined the
      experience of two institutions to better delineate which patients may benefit
      from adjuvant chemoradiation. METHODS: Patients who underwent curative surgery
      for ampullary carcinoma at the Johns Hopkins Hospital (n=290; 1992-2007) and at
      the Mayo Clinic (n=130; 1977-2005) were reviewed. Patients with <60 days of
      follow-up, metastatic disease at surgery, or insufficient pathologic data were
      excluded. The final combined study consisted of 186 patients (n=104 Johns
      Hopkins, n=82 Mayo). Most patients received 5-FU based chemoradiation with
      conformal radiation. Cox proportional hazards models were used for survival
      analysis. RESULTS: Median overall-survival was 39.9 months with 2- and 5-year
      survival rates of 62.4% and 39.1%. On univariate analysis, adverse prognostic
      factors for overall survival included T3/T4 stage disease (RR=1.86, p=0.002),
      node positive status (RR=3.18, p<0.001), and poor histological grade (RR=1.69,
      p=0.011). Patients who received adjuvant chemoradiation (n=66) vs. surgery alone
      (n=120) showed a higher rate of T3/T4 stage disease (57.6% vs. 30.8%, P<0.001),
      lymph node involvement (72.7% vs. 30.0%, P<0.001), and close or positive margins
      (4.6% vs. 0.0%, P=0.019). Five year survival rates among node negative and node
      positive patients were 58.7% and 18.4% respectively. When compared with surgery
      alone, use of adjuvant chemoradiation improved survival among node positive
      patients (mOS 32.1 vs. 15.7 mos, 5 yr OS: 27.5% vs. 5.9%; RR=0.47, P=0.004).
      After adjusting for adverse prognostic factors on multivariate analysis, patients
      treated with adjuvant chemoradiation demonstrated a significant survival benefit
      (RR=0.40, P<0.001). Disease relapse occurred in 37.1% of all patients, most
      commonly metastatic disease in the liver or peritoneum. CONCLUSIONS: Node
      positive patients with resected ampullary adenocarcinoma may benefit from 5-FU
      based adjuvant chemoradiation. Since a significant proportion of patients develop
      metastatic disease, there is a need for more effective systemic treatment.

PMID- 21951379
TI  - Impact of stroke on health-related quality of life in diverse cultures: the
      Berlin-Ibadan multicenter international study.
AB  - BACKGROUND: Various studies have reported discordant profiles of health-related
      quality of life (HRQOL) after stroke. The aims of this study, the first of its
      kind, were to determine the real impact of stroke on HRQOL across diverse
      cultures; and to compare HRQOL between stroke patients and healthy adults, and
      across stroke severity strata. METHODS: 100 stroke patients and 100 apparently
      healthy adults (AHAs) in Nigeria; as well as 103 stroke and 50 AHAs in Germany
      participated. Stroke severity was measured using the National Institute of Health
      Stroke Scale, Stroke Levity Scale and modified Rankin scale. HRQOL was evaluated
      using the HRQOL In Stroke Patients (HRQOLISP) measure, a holistic multiculturally
      validated measure with seven therapeutically-relevant domains distributed into
      two spheres. RESULTS: Domains within the spiritual sphere were considered more
      important by stroke patients. In both countries, stroke patients significantly
      (0.00001 < p < 0.004) had worse HRQOL than AHAs in all domains within the
      physical sphere. This was not so for the spiritual sphere. Consistently, stroke
      severity correlated significantly with all domains in the physical sphere unlike
      the spiritual sphere. In diverse cultures, the correlation coefficients between
      HRQOL and all indices of stroke severity revealed a decremental trend from the
      physical domain (rho = 0.77, p < 0.00001) to the spiritual domain (rho = 0.01, p
      = 0.893). CONCLUSIONS: Consistently, stroke elicited a decremental response
      across domains, with domains in the spiritual sphere being relatively stroke
      resilient. The potential utility of the relatively preserved spiritual sphere in
      facilitating stroke rehabilitation requires evaluation in diverse cultures.

PMID- 21951380
TI  - Walking the tightrope of bioavailability: growth dynamics of PAH degraders on
      vapour-phase PAH.
AB  - Microbial contaminant degradation may either result in the utilization of the
      compound for growth or act as a protective mechanism against its toxicity.
      Bioavailability of contaminants for nutrition and toxicity has opposite
      consequences which may have resulted in quite different bacterial adaptation
      mechanisms; these may particularly interfere when a growth substrate causes
      toxicity at high bioavailability. Recently, it has been demonstrated that a high
      bioavailability of vapour-phase naphthalene (NAPH) leads to chemotactic movement
      of NAPH-degrading Pseudomonas putida (NAH7) G7 away from the NAPH source. To
      investigate the balance of toxic defence and substrate utilization, we tested the
      influence of the cell density on surface-associated growth of strain PpG7 at
      different positions in vapour-phase NAPH gradients. Controlled microcosm
      experiments revealed that high cell densities increased growth rates close (<2
      cm) to the NAPH source, whereas competition for NAPH decreased the growth rates
      at larger distances despite the high gas phase diffusivity of NAPH. At larger
      distance, less microbial biomass was likewise sustained by the vapour-phase NAPH.
      Such varying growth kinetics is explained by a combination of bioavailability
      restrictions and NAPH-based inhibition. To account for this balance, a novel,
      integrated 'Best Equation' describing microbial growth influenced by substrate
      availability and inhibition is presented.

PMID- 21951381
TI  - Invariable biomass-specific primary production of taxonomically discrete
      picoeukaryote groups across the Atlantic Ocean.
AB  - Oceanic photosynthetic picoeukaryotes (< 3 um) are responsible for > 40% of total
      primary production at low latitudes such as the North-Eastern tropical Atlantic.
      In the world ocean, warmed by climate changes, the expected gradual shift towards
      smaller primary producers could render the role of photosynthetic picoeukaryotes
      even more important than they are today. Little is still known, however, about
      how the taxonomic composition of this highly diverse group affects primary
      production at the basin scale. Here, we combined flow cytometric cell sorting,
      NaH14CO3 radiotracer incubations and class-specific fluorescence in situ
      hybridization (FISH) probes to determine cell- and biomass-specific inorganic
      carbon fixation rates and taxonomic composition of two major photosynthetic
      picoeukaryote groups on a ~7500-km-long latitudinal transect across the Atlantic
      Ocean (Atlantic Meridional Transect, AMT19). We show that even though larger
      cells have, on average, cell-specific CO2 uptake rates ~5 times higher than the
      smaller ones, the average biomass-specific uptake is statistically similar for
      both groups. On the other hand, even at a high taxonomic level, i.e. class, the
      contributions to both groups by Prymnesiophyceae, Chrysophyceae and Pelagophyceae
      are significantly different (P < 0.001 in all cases). We therefore conclude that
      these group's carbon fixation rates are independent of the taxonomic composition
      of photosynthetic picoeukaryotes across the Atlantic Ocean. Because the above
      applies across different oceanic regions the diversity changes seem to be a
      secondary factor determining primary production.

PMID- 21951382
TI  - Exome sequencing identifies a novel missense variant in RRM2B associated with
      autosomal recessive progressive external ophthalmoplegia.
AB  - BACKGROUND: Whole-exome sequencing using next-generation technologies has been
      previously demonstrated to be able to detect rare disease-causing variants.
      Progressive external ophthalmoplegia (PEO) is an inherited mitochondrial disease
      that follows either autosomal dominant or recessive forms of inheritance (adPEO
      or arPEO). AdPEO is a genetically heterogeneous disease and several genes,
      including POLG1 and C10orf2/Twinkle, have been identified as responsible genes.
      On the other hand, POLG1 was the only established gene causing arPEO with
      mitochondrial DNA deletions. We previously reported a case of PEO with
      unidentified genetic etiology. The patient was born of a first-cousin marriage.
      Therefore, the recessive form of inheritance was suspected. RESULTS: To identify
      the disease-causing variant in this patient, we subjected the patient's DNA to
      whole-exome sequencing and narrowed down the candidate variants using public data
      and runs of homozygosity analysis. A total of 35 novel, putatively functional
      variants were detected in the homozygous segments. When we sorted these variants
      by the conservation score, a novel missense variant in RRM2B, whose heterozygous
      rare variant had been known to cause adPEO, was ranked at the top. The list of
      novel, putatively functional variants did not contain any other variant in genes
      encoding mitochondrial proteins registered in MitoCarta. CONCLUSIONS: Exome
      sequencing efficiently and effectively identified a novel, homozygous missense
      variant in RRM2B, which was strongly suggested to be causative for arPEO. The
      findings in this study indicate arPEO to be a genetically heterogeneous disorder,
      as is the case for adPEO.

PMID- 21951383
TI  - Obesity and cardiovascular disease risk among Turkish and Moroccan migrant groups
      in Europe: a systematic review.
AB  - Migrants from Turkey and Morocco are among the largest ethnic minority groups in
      several European countries. In this review, we aimed to systematically search,
      assess and describe the available literature on cardiovascular disease (CVD),
      obesity and other endogenous cardiovascular risk factors among these groups.
      Although the number of publications covering this topic among Turkish and
      Moroccan migrants has increased in the past decades, studies among these groups,
      especially the Moroccan, are still limited. There is a particular lack of
      information on CVD mortality and morbidity rates. Furthermore, studies are often
      hampered by low participation rates, small sample sizes and self-reported data.
      This further complicates drawing sound conclusions on CVD and risk factors among
      these migrant groups. The results with regard to CVD morbidity and mortality
      rates are inconclusive. With regard to CVD risk factors, we tentatively conclude
      that obesity and diabetes are more common among Turkish and Moroccan migrant
      groups in Europe than the western European population. In the Turkish population
      there is also a fair amount of evidence for unfavourable high-density lipoprotein
      cholesterol levels. However, more research on this topic among these major ethnic
      minorities is of high importance.

PMID- 21951384
TI  - Guidelines for the management of adult lower respiratory tract infections-
      summary.
AB  - This document is an update of Guidelines published in 2005 and now includes
      scientific publications through to May 2010. It provides evidence-based
      recommendations for the most common management questions occurring in routine
      clinical practice in the management of adult patients with LRTI. Topics include
      management outside hospital, management inside hospital (including community
      acquired pneumonia (CAP), acute exacerbations of COPD (AECOPD), acute
      exacerbations of bronchiectasis) and prevention. The target audience for the
      Guideline is thus all those whose routine practice includes the management of
      adult LRTI.

PMID- 21951386
TI  - Acute renal failure in acute poisoning: prospective study from a tertiary care
      centre of South India.
AB  - BACKGROUND: Cases of people presenting with poisoning are likely to develop acute
      renal failure (ARF), which may be due to multiple mechanisms/aetiologies. These
      cases need careful observation and appropriate treatment. OBJECTIVE: To find the
      risk of ARF among acute poisoning cases, identify the underlying causes and to
      analyse the outcome. MATERIAL AND METHODS: In this prospective study with nested
      case control, 1,250 cases admitted to the Poison Control, Training and Research
      Centre of Government General Hospital, Madras Medical College were monitored and
      evaluated for development of ARF. Patients with history of diabetes/hypertension,
      known chronic kidney disease, chronic NSAID therapy, those on drugs that increase
      serum creatinine by inhibiting creatinine secretion and other co-morbid illnesses
      were excluded. Data were interpreted after subjecting them to bivariate logistic
      regression and then step wise multivariate analysis. RESULTS: Thirty-two cases
      developed ARF. Twenty-four were due to snake bite, the rest due to chemical
      poisons. Chances of developing ARF were greater (6.15%) among the poisoning due
      to bites and stings than chemical poisoning (0.9%). Five in the former and seven
      in the latter expired. Among cases bitten by snakes, only 22 (7%) cases bitten by
      Russell Viper Daboia russelii developed renal failure. Copper sulphate and rat
      killer poisonings were the commonest causes of chemical induced ARF, dichromate,
      indigenous medicines and vasmol 33 (paraphenelyne diamine) were the least causes
      for ARF. None of the patients with organophosphate developed ARF nor did any of
      the 150 admitted for overdose of medicines developed ARF. CONCLUSION: The risk of
      ARF among the cases of poisoning was 2.5%. The outcome of ARF among bites and
      stings was better than chemical poisoning, and the difference was highly
      significant (p= 0.005, OR = 0.04-1.0, 95% CI = 0.004-0.38). Early recognition and
      appropriate measures reduce the occurrence of ARF.

PMID- 21951385
TI  - Guidelines for the management of adult lower respiratory tract infections--full
      version.
AB  - This document is an update of Guidelines published in 2005 and now includes
      scientific publications through to May 2010. It provides evidence-based
      recommendations for the most common management questions occurring in routine
      clinical practice in the management of adult patients with LRTI. Topics include
      management outside hospital, management inside hospital (including community
      acquired pneumonia (CAP), acute exacerbations of COPD (AECOPD), acute
      exacerbations of bronchiectasis) and prevention. Background sections and graded
      evidence tables are also included. The target audience for the Guideline is thus
      all those whose routine practice includes the management of adult LRTI.

PMID- 21951387
TI  - Current evidence for a role of GLP-1 in Roux-en-Y gastric bypass-induced
      remission of type 2 diabetes.
AB  - Weight-reducing surgical procedures such as Roux-en-Y gastric bypass (RYGB) have
      proven efficient as means of decreasing excess body weight. Furthermore, some
      studies report that up to 80% of patients with type 2 diabetes mellitus (T2DM)
      undergoing RYGB experience complete remission of their T2DM. Interestingly, the
      majority of remissions occur almost immediately following the operation and long
      before significant weight loss has taken place. Following RYGB, dramatic
      increases in postprandial plasma concentrations of the incretin hormone glucagon
      like peptide-1 (GLP-1) have been recorded, and the known antidiabetic effects of
      GLP-1 are thought to be key mediators in RYGB-induced remission of T2DM. However,
      the published studies on the impact of RYGB on GLP-1 secretion are few, small and
      often not controlled properly. Furthermore, mechanistic studies delineating the
      role of endogenous GLP-1 secretion in RYGB-induced remission of T2DM are lacking.
      This article critically evaluates the current evidence for a role of GLP-1 in
      RYGB-induced remission of T2DM.

PMID- 21951388
TI  - An overview of cancer/testis antigens expression in classical Hodgkin's lymphoma
      (cHL) identifies MAGE-A family and MAGE-C1 as the most frequently expressed
      antigens in a set of Brazilian cHL patients.
AB  - ABSTRACT:  BACKGROUND: Cancer/testis antigens are considered potential targets
      for immunotherapy due to their tumor-associated expression pattern. Although
      recent studies have demonstrated high expression of CT45 in classical Hodgkin's
      lymphomas (cHL), less is known about the expression pattern of other families of
      CTAs in cHL. We aim to evaluate the expression of MAGE-A family, MAGE-C1/CT7,
      MAGE-C2/CT10, NY-ESO1 and GAGE family in cHL and to correlate their expression
      with clinical and prognostic factors in cHL. METHODS: Tissue microarray was
      generated from 38 cHL archival cases from Pathology Department of Universidade
      Federal de Sao Paulo. Immunohistochemistry (IHC) was done using the following
      panel of antibodies: MAGE-A family (MA454, M3H67, 57B and 6C1), GAGE (#26), NY
      ESO-1 (E978), MAGE-C1/CT7 (CT7-33) and MAGE-C2/CT10 (CT10#5). RESULTS: We found
      CTA expression in 21.1% of our cHL series. Among the tested CTAs, only MAGE-A
      family 7/38 (18.4%) and MAGE-C1/CT7 5/38 (13.2%) were positive in our cHL
      samples. We found higher CTA positivity in advanced stage (28.6%) compared to
      early stage (11.8%) disease, but this difference was not statistically
      significant. Analysis of other clinicopathological subgroups of cHL including
      histological subtypes, EBV status and response to treatment also did not
      demonstrate statistical significant differences in CTA expression. CONCLUSION: We
      found CTA expression in 21.1% of cHL samples using our panel. Our preliminary
      findings suggest that from all CTAs included in this study, MAGE-A family and
      MAGE-C1/CT7 are the most interesting ones to be explored in further studies.

PMID- 21951389
TI  - Favorable factors for re-treatment with pegylated interferon alpha2a plus
      ribavirin in patients with high viral loads of genotype 1 hepatitis C virus.
AB  - AIM:   Effect of re-treatment for pegylated interferon (PEG-IFN) plus ribavirin
      was not fully evaluated. We examined the effects of re-treatment with PEG-IFN
      plus ribavirin in patients with high viral loads of genotype 1 hepatitis C virus
      who failed to achieve a sustained virological response (SVR) with combination
      therapy. METHODS:   We examined 38 patients who were re-treated with PEG-IFN
      alpha2a plus ribavirin for more than 60 weeks, among whom 14 were non-responders
      and 24 were relapsers after previous treatment with PEG-IFN alpha2b plus
      ribavirin. IL28B genotyping was done in 21 patients. RESULTS:   The overall SVR
      rate was 34%. Analysis of baseline characteristics showed that the relapsers had
      a significantly higher SVR rate than the non-responders (50.0%, 12/24 vs. 7.1%,
      1/14, respectively, P = 0.012) The SVR rates of re-treated patients who had
      turned hepatitis C virus (HCV) RNA-negative at weeks 8, 12, 24, and 48 of the
      previous therapy were 67% (4/6), 67% (4/6), 29% (2/7), and 25% (1/4),
      respectively. Re-treatment achieved an SVR in five of 12 patients with IL28B
      major alleles and three of nine patients with IL28B minor alleles. During the re
      treatment, patients with complete viral suppression at week-12 achieved a
      significantly higher SVR rate (P = 0.001). CONCLUSIONS:   Re-treatment with PEG
      IFN alpha2a plus ribavirin therapy is effective in patients who relapse after a
      course of PEG-IFN alpha2b plus ribavirin therapy. Re-treatment is a particularly
      useful option for patients who achieve early viral clearance during previous
      therapy.

PMID- 21951390
TI  - Facial reversal reaction: a dermatological emergency.

PMID- 21951391
TI  - Testicular function after radiotherapy for rectal cancer--a review.
AB  - INTRODUCTION: Eighty percent of all male rectal cancer patients are sexually
      active at the time of diagnosis. Because of modern multimodal therapy many can
      expect long-term survival. The testes can be exposed to scattered or direct
      radiation during radiotherapy, depending on their position in relation to the
      targeted volume. AIM: This review analyzes the current literature providing data
      on testicular exposure to radiation during radiotherapy for rectal cancer and the
      consequences on testicular function. METHODS: A systematic search was conducted
      in PubMed, Embase, and Cochrane. Ten original articles providing data on
      testicular exposure to radiation and testicular function in men with primary
      rectal cancer were included for qualitative synthesis. MAIN OUTCOME MEASURES:
      Data on testicular exposure to radiation and testosterone levels in men with
      rectal cancer are reported. RESULTS: On average, the testes were exposed to 0.24
      8.4 Gy during long-course radiotherapy for rectal cancer. Testosterone levels
      after radiation were significantly lower compared with pretreatment levels or
      compared with patients treated with surgery alone. After radiotherapy, the
      absolute risk increase was 0.17-0.30 for posttreatment testosterone levels below
      8 nmol/L. In the largest study, the relative risk was 2.7 for testosterone levels
      below 8 nmol/L for men treated with radiotherapy compared with men treated with
      surgery alone. CONCLUSION: Current data generate three hypotheses: (i) during
      long-course radiotherapy for rectal cancer, the testes can be exposed to direct
      and/or scattered radiation; (ii) men treated with radiotherapy seem at risk to
      develop testicular dysfunction with decreased serum testosterone levels compared
      with both pretreatment values and men treated with surgery alone; and (iii) a
      decrease in testosterone levels (<8 nmol/L) may precipitate specific symptoms
      caused by testosterone deficiency such as impaired physical, psychological, and
      sexual function after treatment.

PMID- 21951392
TI  - Amyloid plaques dissociate pentameric to monomeric C-reactive protein: a novel
      pathomechanism driving cortical inflammation in Alzheimer's disease?
AB  - Beta-amyloid (Abeta) plaques and local inflammation are central to the
      pathogenesis of Alzheimer's disease. Although an association between circulating
      pentameric C-reactive protein (pCRP) and Alzheimer's disease has been reported no
      pathomechanistic link has been established. We hypothesized that Abeta plaques
      induce the dissociation of pCRP to individual monomers (mCRP), which possess
      strong pro-inflammatory properties not shared with pCRP and localizing
      inflammation to Alzheimer's plaques. pCRP was incubated with Abeta plaques
      generated in vitro and with non-aggregated Abeta(42) peptide. pCRP dissociation
      to mCRP was found only when co-incubated with Abeta plaques. Furthermore,
      sections of frontal cortex from brains of patients with and without Alzheimer's
      disease were stained with antibodies specific for mCRP and pCRP. There was
      significantly more mCRP in the cortex of Alzheimer's disease patients (P <=
      0.01). In contrast, there was no significant difference in pCRP staining. These
      findings establish that Abeta plaques possess a previously unrecognized potential
      to dissociate pentameric CRP to monomeric CRP. The existence of mCRP but not pCRP
      in the brains of Alzheimer's disease patients strongly indicates that this newly
      described biological effect of Abeta plaques is relevant in Alzheimer
      pathobiology; potentially localizing and amplifying inflammation via the strong
      pro-inflammatory effects of locally generated mCRP.

PMID- 21951393
TI  - Functional and phenotypical alterations of polymorphonuclear cells in Sezary
      syndrome patients.
AB  - Sezary syndrome (SS), the leukemic variant of cutaneous T-cell lymphoma (CTCL),
      has a poor prognosis and infections represent the most frequent cause of death.
      Polymorphonucleate granulocytes (PMNs) constitute an essential part of the innate
      immune system: their phagocytic and killing activity against pathogens is
      mediated by the interactions between Toll-like receptors (TLRs) and the Pathogen
      associated molecular patterns (PAMPs). The aim of this study was to investigate
      PMN functional activity and phenotype in SS patients and their correlation with
      the onset of infectious complications. This prospective study enrolled 18
      consecutive SS patients; PMN functional activity was evaluated by phagocytosis
      and intracellular killing tests towards Klebsiella pneumoniae. Flow-cytometry was
      applied to analyze PMN phenotype. PMNs from SS patients displayed a reduced
      phagocytic activity and intracellular killing against K. pneumoniae at 30 min and
      60 min, more pronounced in SS patients with recurrent infections. CD11b and CD66b
      median fluorescence intensity (MFI) was significantly higher in SS than in
      healthy subjects, whereas CD62L MFI was decreased. No significant differences in
      TLR2, 4, 8 and 9 percentage expression or MFI were found. An increased TLR5
      percentage expression was documented. The impairment in PMN functional activities
      in SS could favour the immune-suppression and raise infection risk.

PMID- 21951394
TI  - Radiopacity of intracerebral hemorrhage correlates with perihemorrhagic edema.
AB  - BACKGROUND: Experimental evidence indicates that iron plays a key role in edema
      formation after intracerebral hemorrhage (ICH). We investigated the relationship
      between ICH radiopacity on CT as a marker of hematoma iron content and
      perihemorrhagic edema (PHE) after ICH. METHODS: We retrospectively investigated
      patients with spontaneous lobar and ganglionic supratentorial ICH who received
      follow-up CT scans during the first 7days after symptom onset (d1, d2-4, d5-7).
      Measurements of ICH and edema volumes were taken using a semiautomatic threshold
      based volumetric algorithm. Radiopacity of the blood clot was determined using
      the mean Hounsfield unit (HU) count of the ICH. RESULTS: A total of 117 patients
      aged 71.92+/-11.55years with spontaneous ICH (34.63+/-32.44ml) were included in
      the analysis. Mean ICH radiopacity was 59.7+/-3.4HU. We found significantly
      larger relative PHE at d2-4 (1.7+/-0.9 vs. 1.3+/-0.8; P=0.032) and d5-7 (2.0+/
      1.3 vs. 1.3+/-0.9; P=0.007) and larger peak relative PHE (2.3+/-1.6 vs. 1.6+/
      1.1; P=0.006) in patients with ICH radiopacity >60HU (n=59), as compared to
      patients with ICH radiopacity <60HU (n=58). CONCLUSIONS: Higher ICH radiopacity,
      reflecting higher in vivo hematoma iron content, is associated with more PHE
      after ICH.

PMID- 21951396
TI  - Prevalence and severity of pulmonary hypertension in asymptomatic rural residents
      with schistosomal infection in the Nile Delta.
AB  - OBJECTIVES: Millions of people in the developing world may suffer from pulmonary
      hypertension (PHTN) because of preexisting infectious conditions. Schistosomiasis
      can cause pulmonary lesions that eventually lead to PHTN. The aim of this study
      was to assess the prevalence of PHTN together with assessment of right
      ventricular (RV) function in asymptomatic rural residents previously infected
      with schistosomiasis. METHODS: Three hundred and seventy asymptomatic people from
      an endemic area in the Nile Delta were screened for antibodies against
      schistosomiasis. All were scheduled for transthoracic echocardiographic study to
      assess pulmonary artery systolic (PASP) and diastolic (PADP) pressures as well as
      RV function. PASP >40 mmHg was considered elevated. RESULTS: Seropositive (SP)
      and seronegative (SN) groups had comparable age and body mass index. PASP >40
      mmHg was met in 18 subjects (Range 42-72 mmHg) (8.6%) of SP group and in no
      subject in SN group (P = 0.000). Compared with SN group, the SP group had higher
      mean values of PASP (30 +/- 10 vs. 24 +/- 7 mmHg, P < 0.000) and PADP (12 +/- 4
      vs. 9 +/- 3 mmHg, P < 0.000). The SP group had lower values of RV ejection
      fraction. CONCLUSION: Prevalence of PHTN as detected by echocardiography in
      asymptomatic rural residents with schistosomiasis in Nile Delta is low with mild
      affection of RV function.

PMID- 21951397
TI  - Residual malformations and leg length discrepancy after treatment of fibular
      hemimelia.
AB  - BACKGROUND: Fibular hemimelia has been reported as the most common congenital
      longitudinal deficiency of the long bones. Previous studies have focused on the
      best treatment options for this congenital condition. There is very little to our
      knowledge in the literature focused on residual persisting malformations and leg
      length discrepancy after treatment. METHODS: Seven patients presenting fibular
      hemimelia in eight fibulae received treatment between years 1988 and 2001. Pre
      treatment average leg length discrepancy was 5.3 cm. All patients presented
      associated congenital deformities of the ipsilateral leg. Six patients received
      surgical treatment. Average post-treatment follow up was 9.7 years. Residual
      malformations and leg length discrepancy were recorded for all patients. It is a
      retrospective case series study at one institution by two of the presenting
      authors as senior surgeons. RESULTS: Average leg length gained after successful
      bone lengthening in six patients was 5.06 cm. Although there was a significant
      functional improvement, a number of residual malformations and leg length
      inequality was recorded. Residual average leg length discrepancy of 3.1 cm was
      observed in five patients who completed surgical treatment. Five patients
      presented a limp. Residual anterior-medial bowing of the tibia was observed in
      four patients. Calf atrophy was present in all seven patients. Valgus deformity
      of the ankle was remained in two patients. CONCLUSIONS: Treatment of fibular
      hemimelia, even in cases graded as successful, showed to be accompanied by a
      number of persisting residual deformities and recurrent leg length inequality.
      Although the number of patients is limited, the high rate of this phenomenon is
      indicative of the significance of the report. The family and the patients
      themselves should have the right expectations and will be more co-operative when
      well informed about this instance. A report of common post-treatment residual
      deformities should be valuable in best possible treatment planning of fibular
      hemimelia.

PMID- 21951398
TI  - Ex vivo hepatic venography for hepatocellular carcinoma in livers explanted for
      liver transplantation.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is supposed to have a venous drainage
      system to a portal vein, which makes intrahepatic metastasis possible. However,
      the mechanism of extrahepatic recurrence, including the possibility of a direct
      route to the systemic circulation from the HCC nodules, remains unclear.
      Therefore, we performed retrograde hepatic venography for HCC in livers that had
      been explanted for liver transplantation in order to explore the possible direct
      connection between the hepatic vein and HCC nodules. METHODS: Of 105 living-donor
      liver transplantations (LDLT) performed up to July, 2009 at the Department of
      Surgery, Nagasaki University Hospital, dynamic hepatic venography was performed
      with contrast media under fluoroscopy for the most recent 13 cases with HCC. The
      presence of a tumor stain for each HCC case was evaluated and compared with the
      histological findings of HCC. RESULTS: Hepatic venography revealed a tumor stain
      in 2 of 13 cases (15%). Neither showed any microscopic tumor invasion of HCC into
      the hepatic vein. In the other 11 cases, there were 4 microscopic portal venous
      invasions and 2 microscopic hepatic venous invasions. No patients have shown HCC
      recurrence in follow-up (median period, 13 months). CONCLUSION: Using ex vivo
      hepatic venography, a direct connection to the hepatic vein from HCC in whole
      liver was revealed in 2 cases without demonstrated histopathological invasion to
      hepatic vein for the first time in the literature. The finding suggests that
      there is direct spillage of HCC cells into the systemic circulation via hepatic
      vein.

PMID- 21951399
TI  - Stem cell approaches for diabetes: towards beta cell replacement.
AB  - Stem cells hold great promise for pancreatic beta cell replacement therapy for
      diabetes. In type 1 diabetes, beta cells are mostly destroyed, and in type 2
      diabetes beta cell numbers are reduced by 40% to 60%. The proof-of-principle that
      cellular transplants of pancreatic islets, which contain insulin-secreting beta
      cells, can reverse the hyperglycemia of type 1 diabetes has been established, and
      there is now a need to find an adequate source of islet cells. Human embryonic
      stem cells can be directed to become fully developed beta cells and there is
      expectation that induced pluripotent stem (iPS) cells can be similarly directed.
      iPS cells can also be generated from patients with diabetes to allow studies of
      the genomics and pathogenesis of the disease. Some alternative approaches for
      replacing beta cells include finding ways to enhance the replication of existing
      beta cells, stimulating neogenesis (the formation of new islets in postnatal
      life), and reprogramming of pancreatic exocrine cells to insulin-producing cells.
      Stem-cell-based approaches could also be used for modulation of the immune system
      in type 1 diabetes, or to address the problems of obesity and insulin resistance
      in type 2 diabetes. Herein, we review recent advances in our understanding of
      diabetes and beta cell biology at the genomic level, and we discuss how stem-cell
      based approaches might be used for replacing beta cells and for treating
      diabetes.

PMID- 21951400
TI  - World Stroke Day special edition: where are we six-years on?

PMID- 21951401
TI  - IJS announces journal series on stroke, cognition and vascular dementia.

PMID- 21951402
TI  - World stroke day.

PMID- 21951403
TI  - World stroke day editorial.

PMID- 21951405
TI  - The future of basic science research and stroke: hubris and translational stroke
      research.

PMID- 21951406
TI  - Is a prestroke modified Rankin Scale sensible?

PMID- 21951407
TI  - Can stroke cause neurodegenerative dementia?
AB  - Stroke and dementia have typically been housed in different taxonomies. They are
      considered to be exemplars of very different forms of brain injury: stroke as an
      acute vascular injury and dementia as a progressive degenerative disease. Yet
      there is definite overlap between the two conditions: stroke increases the
      likelihood of developing dementia. Recent work has confirmed that vascular risk
      factors such as diabetes and hypertension predispose to dementia. However, in the
      absence of any clear findings of a direct pathway from stroke to degenerative
      dementia, the separation has persisted. In this review, we summarize the evidence
      relating to whether stroke can initiate or promote degenerative dementia and, in
      particular, Alzheimer's disease. The evidence comes from autopsy studies, from
      brain imaging studies, from studies of patients with symptomatic stroke and from
      studies in CADASIL. A number of studies have demonstrated that stroke can lead to
      changes in brain volume and cognitive performance, although generally of a
      different profile to the atrophy and cognitive decline seen in Alzheimer's
      disease. Much of the evidence is circumstantial, and does little to support a
      claim that stroke triggers neurodegenerative dementia. The question, then,
      remains open. None of the studies reviewed included the necessary longitudinal
      follow-up of stroke patients incorporating cognitive assessment, imaging and
      pathology. Given the high prevalence and substantial burden of dementia, there is
      much to be gained from identifying prognostic markers and it remains an exciting
      idea that we might be able to identify a subgroup of stroke patients who are at
      high risk.

PMID- 21951408
TI  - Constraint-induced movement therapy for the upper paretic limb in acute or sub
      acute stroke: a systematic review.
AB  - Constraint-induced movement therapy is a commonly used intervention to improve
      upper limb function after stroke. However, the effectiveness of constraint
      induced movement therapy and its optimal dosage during acute or sub-acute stroke
      is still under debate. To examine the literature on the effects of constraint
      induced movement therapy in acute or sub-acute stroke. A literature search was
      performed to identify randomized, controlled trials; studies with the same
      outcome measure were pooled by calculating the mean difference. Separate
      quantitative analyses for high-intensity and low-intensity constraint-induced
      movement therapy were applied when possible. Five randomized, controlled trials
      were included, comprising 106 participants. The meta-analysis demonstrated
      significant mean differences in favor of constraint-induced movement therapy for
      the Fugl-Meyer arm, the Action Research Arm Test, the Motor Activity Log, Quality
      of Movement and the Grooved Pegboard Test. Nonsignificant mean difference in
      favor of constraint-induced movement therapy were found for the Motor Activity
      Log, Amount of Use. Separate analyses for high-intensity and low-intensity
      constraint-induced movement therapy resulted in significant favorable mean
      differences for low-intensity constraint-induced movement therapy for all outcome
      measures, in contrast to high-intensity constraint-induced movement therapy. This
      meta-analysis demonstrates a trend toward positive effects of high-intensity and
      low-intensity constraint-induced movement therapy in acute or sub-acute stroke,
      but also suggests that low-intensity constraint-induced movement therapy may be
      more beneficial during this period than high-intensity constraint-induced
      movement therapy. However, these results were based on a small number of studies.
      Therefore, more trials are needed applying different doses of therapy early after
      stroke and a better understanding is needed about the different time windows in
      which underlying mechanisms of recovery operate.

PMID- 21951410
TI  - Toward understanding the atrial septum in cryptogenic stroke.
AB  - Ischemic stroke in younger people is common, and often remains unexplained. There
      is a well-documented association between unexplained stroke in younger people,
      and the presence of a patent foramen ovale. Therefore, in the absence of a clear
      cause of stroke, the heart is often assessed in detail for such lower risk causes
      of stroke. This usually involves imaging with a transesophageal echo, and
      investigation for a right-to-left shunt. An understanding of the anatomy of the
      atrial septum, and its associated abnormalities, is important for the stroke
      neurologist charged with decision making regarding appropriate secondary
      prevention. In this paper, we review the development and anatomy of the right
      heart with a focus on patent foramen ovale, and other associated abnormalities.
      We discuss how the heart can be imaged in the case of unexplained stroke, and
      provide examples. Finally, we suggest a method of investigation, in light of the
      recent European Association of Echocardiography guidance. Our aim is to provide
      the neurologist with an understanding on how the heart can be investigated in
      unexplained stroke, and the significance of abnormalities detected.

PMID- 21951409
TI  - Is the spontaneously hypertensive stroke prone rat a pertinent model of sub
      cortical ischemic stroke? A systematic review.
AB  - The spontaneously hypertensive stroke prone rat is best known as an inducible
      model of large artery stroke. Spontaneous strokes and stroke propensity in the
      spontaneously hypertensive stroke prone rat are less well characterized; however,
      could be relevant to human lacunar stroke. We systematically reviewed the
      literature to assess the brain tissue and small vessel pathology underlying the
      spontaneous strokes of the spontaneously hypertensive stroke prone rat. We
      searched systematically three online databases from 1970 to May 2010; excluded
      duplicates, reviews, and articles describing the consequences of induced middle
      cerebral artery occlusion or noncerebral pathology; and recorded data describing
      brain region and the vessels examined, number of animals, age, dietary salt
      intake, vascular and tissue abnormalities. Among 102 relevant studies, animals
      sacrificed after developing stroke-like symptoms displayed arteriolar wall
      thickening, subcortical lesions, enlarged perivascular spaces and cortical
      infarcts and hemorrhages. Histopathology, proteomics and imaging studies
      suggested that the changes not due simply to hypertension. There may be
      susceptibility to endothelial permeability increase that precedes arteriolar wall
      thickening, degeneration and perivascular tissue changes; systemic inflammation
      may also precede cerebrovascular changes. There were very few data on venules or
      tissue changes before hypertension. The spontaneously hypertensive stroke prone
      rat shows similar features to human lacunar stroke and may be a good spontaneous
      model of this complex human disorder. Further studies should focus on structural
      changes at early ages and genetics to identify factors that predispose to
      vascular and brain damage.

PMID- 21951411
TI  - Preventing recurrence of thromboembolic events through coordinated treatment in
      the District of Columbia.
AB  - RATIONALE: PROTECT DC examines whether stroke navigators can improve
      cardiovascular risk factors in urban underserved individuals newly hospitalized
      for stroke or ischemic attack. Within one-year of hospital discharge, up to one
      third of patients no longer adhere to secondary prevention behaviors. Adherence
      rates are lower in minority-underserved groups, contributing to health
      disparities. In-hospital programs increase use of stroke prevention therapies but
      may not be as successful in underserved individuals. In these groups, low
      literacy, limited healthcare access, and sparse community resources may reduce
      adherence. Lay community health workers (navigators) improve adherence in other
      illnesses through education and assisting in overcoming barriers to achieving
      desired health behaviors and obtaining needed healthcare services. AIMS AND
      DESIGN: PROTECT DC is a Phase II, single-blind, randomized, controlled trial
      comparing in-hospital education plus stroke navigators to usual care. Atherogenic
      ischemic stroke and transient ischemic attack survivors are recruited from
      Washington, DC hospitals. Navigators meet with participants during the index
      hospitalization, perform home visits, and meet by phone. They focus on stroke
      education, medication compliance, and overcoming practical barriers to adherence.
      The interventions are driven by the theories of reasoned action and planned
      behavior. STUDY OUTCOMES: The primary dependent measure is a summary score of
      four objective measures of stroke risk factor control: systolic blood pressure,
      low-density lipoprotein, hemoglobin Hb A1C, and antiplatelet agent pill counts.
      Secondary outcomes include stroke knowledge, exercise, dietary modification, and
      smoking cessation. CONCLUSION: PROTECT DC will determine whether a Phase III
      trial of stroke navigation for urban underserved individuals to improve adherence
      to secondary stroke prevention behaviors is warranted.

PMID- 21951412
TI  - Standard medical management in secondary prevention of ischemic stroke in China
      (SMART).
AB  - BACKGROUND: Although guidelines for secondary ischemic stroke have been
      developed, there is a gap between guidelines and clinic practice. AIMS: This
      study will investigate the current status of secondary ischemic stroke prevention
      in China, and implement a standard medical program in ischemic stroke and/or
      transient ischemic attack patients, and to examine the feasibility and efficacy
      of the program. DESIGN: This is a multicentre, parallel, randomized, open label,
      controlled trial to evaluate the feasibility and efficacy of a recommended
      guideline based program (SMART) in secondary stroke prevention. Forty-eight sites
      across Mainland China will participate in the trial. The number of enrolled
      patients in the study will be 4074. Primary outcome includes the proportion of
      patients adherent to eligible measures recommend by the SMART program, which is
      derived from current prevention guidelines for ischemic stroke, and the
      proportion of the patients achieving the treatment target. Secondary outcomes
      include new onset ischemic stroke, hemorrhagic stroke, acute coronary syndrome
      and all causes of death. The study has been registered on Clinicaltrials.gov
      (NCT00664846); to date, 3380 patients have been enrolled.

PMID- 21951414
TI  - Stratification with CHA2DS2-VASc score is better than CHADS2 score in reducing
      ischemic stroke risk in patients with atrial fibrillation.

PMID- 21951413
TI  - CXCR4/SDF-1alpha-chemokine regulates neurogenesis and/or angiogenesis within the
      vascular niche of ischemic rats; however, does SDF-1alpha play a role in repair?

PMID- 21951415
TI  - An epidemiological study of stroke and its sub-types in the over 55 Mongolian and
      Han populations in a pastoral area of inner Mongolia.

PMID- 21951417
TI  - Manganese sulfide formation via concomitant microbial manganese oxide and
      thiosulfate reduction.
AB  - The dissimilatory metal-reducing bacterium, Shewanella oneidensis MR-1 produced
      gamma-MnS (rambergite) nanoparticles during the concurrent reduction of MnO2 and
      thiosulfate coupled to H2 oxidation. To investigate effect of direct microbial
      reduction of MnO2 on MnS formation, two MR-1 mutants defective in outer membrane
      c-type cytochromes (DeltamtrC/DeltaomcA and DeltamtrC/DeltaomcA/DeltamtrF) were
      also used and it was determined that direct reduction of MnO2 was dominant
      relative to chemical reduction by biogenic sulfide generated from thiosulfate
      reduction. Although bicarbonate was excluded from the medium, incubations of
      strain MR-1 with lactate as the electron donor produced MnCO3 (rhodochrosite) as
      well as MnS in nearly equivalent amounts as estimated by micro X-ray diffraction
      (micro-XRD) analysis. It was concluded that carbonate released from lactate
      metabolism promoted MnCO3 formation and that Mn(II) mineralogy was strongly
      affected by carbonate ions even in the presence of abundant sulfide and weakly
      alkaline conditions expected to favour the precipitation of MnS. Formation of
      MnS, as determined by a combination of micro-XRD, transmission electron
      microscopy, energy dispersive X-ray spectroscopy, and selected area electron
      diffraction analyses was consistent with equilibrium speciation modelling
      predictions. Biogenic manganese sulfide may be a manganese sink in the Mn
      biogeochemical cycle in select environments such as deep anoxic marine basins
      within the Baltic Sea.

PMID- 21951418
TI  - Negative heterozygosity-fitness correlations observed with microsatellites
      located in functional areas of the genome.
AB  - Genome-wide heterozygosity inferred from neutral markers such as microsatellites
      is often expected to (i) reflect individual inbreeding and (ii) covary positively
      with fitness, generating positive heterozygosity-fitness correlations (HFCs). The
      often forgotten other end of the inbreeding-outbreeding continuum is outbreeding
      depression: past a certain degree of heterozygosity, heterozygotes tend to have
      lower fitness than homozygotes. Outbreeding depression arises from the breakup of
      co-adapted gene complexes and/or the introgression of nonlocally adapted genes.
      Provided that a correlation in heterozygosity exists across loci, outbreeding
      depression will be reflected in negative HFCs. In this issue, Olano-Marin et al.
      (2011a) describe negative heterozygosity-fitness correlations (HFCs) in blue tits
      Cyanistes caeruleus (Fig. 1), whereby heterozygosity has a significant, negative
      effect on female hatching success and recruitment. This study, together with a
      similar study by the same authors published in Evolution (Olano-Marin et al.
      2011b), forms an original contribution in two respects. First, in the same
      population, positive and negative HFCs were recorded, revealing both inbreeding
      and outbreeding depression depending on the trait studied (whereby both processes
      were reliant on unknown, and possibly different, sets of coding loci). Second, a
      large number of microsatellite markers were split into two functional groups:
      microsatellite markers were either designed using zebra finch expressed sequence
      tags (ESTs) or derived using traditional cloning methods and presumed to be
      neutral. Contrasting large classes of loci and their varying levels of
      polymorphism, rather than looking for one locus that would stand out among tens
      of randomly selected markers, pave the way for a more elegant and powerful
      approach to explore how HFCs vary across traits and among regions of the genome.
      [Figure: see text].

PMID- 21951419
TI  - The full path of Janzen-Connell effects: genetic tracking of seeds to adult plant
      recruitment.
AB  - The Janzen-Connell (J-C) model (Janzen 1970; Connell 1971) has been a dominant
      yet controversial paradigm for forest community dynamics for four decades,
      especially in the tropics. With increasing distance from the parent plant, the
      density of dispersed seeds decreases and, because of a reduced impact of distance
      and density-responsive seed and seedling enemies, propagule survival increases,
      resulting in peak recruitment at some distance from the parent and little
      recruitment near adult conspecifics. This spacing generates gaps near adult trees
      for the recruitment of heterospecifics, enhancing species coexistence and species
      richness. Field studies, primarily focused on seeds and young seedlings, have
      repeatedly demonstrated increasing survival with increasing distance from parents
      or decreasing density of propagules (e.g. Clark & Clark 1984; Gilbert et al.
      1994; Swamy & Terborgh 2010). Yet a meta-analysis of distance-dependent propagule
      survival failed to support a general pattern of survival increasing with distance
      from adult conspecifics, suggesting that there is no need for further
      experimental tests of the J-C hypothesis in terms of diversity enhancement
      results are species-specific, not general (Hyatt et al. 2003). However, a lack of
      consistent experimental results is not surprising. The outcome of tests of the
      hypothesis can vary as a function of many factors that can affect successive
      recruitment stages differently (Schupp 1992; Hyatt et al. 2003; Swamy & Terborgh
      2010). This highlights a critical gap-a full test of the J-C model requires data
      demonstrating that effects carry over to recruitment of new reproductive adults,
      yet few studies have gone beyond early stages. There is strong inferential
      evidence that adult trees can show the imprint of J-C effects (e.g. Nathan et al.
      2000; Howe & Miriti 2004), and focal individual modelling has clearly
      demonstrated that J-C effects can operate from sapling through adult stages in a
      significant number of species (Peters 2003). It is likely that such results are
      not unusual, but there have been few attempts to demonstrate J-C spacing at the
      adult stage. In this issue of Molecular Ecology, Steinitz et al. (2011) studied
      the Mediterranean pine Pinus halepensis (Aleppo pine) and combined a unique
      situation with an innovative approach to provide the most elegant demonstration
      yet that adult recruits are spaced further from parents than expected from the
      initial seed distribution, clear evidence of a J-C effect carrying over to
      reproductive adults. A major advancement of this study is that it incorporates
      estimates of the initial patterns of seed dispersal and parentage analysis of
      adult-offspring relationships, illustrating the value of combined field and
      genetic approaches.

PMID- 21951420
TI  - Whole-cell bacterial bioreporter for actively searching and sensing of alkanes
      and oil spills.
AB  - Acinetobacter baylyi ADP1 was found to tolerate seawater and have a special
      ability of adhering to an oil-water interface of 10-80 um emulsified mineral and
      crude oil droplets. These properties make ADP1 an ideal bacterial chassis for
      constructing bioreporters that are able to actively search and sense oil spill in
      water and soils. Acinetobacter baylyi bioreporter ADPWH_alk was developed and
      applied to the detection of alkanes and alkenes in water, seawater and soils.
      Bioreporter ADPWH_alk was able to detect a broad range of alkanes and alkenes
      with carbon chain length from C7 to C36. So far, ADPWH_alk is the only
      bioreporter that is able to detect alkane with carbon chain length greater than
      C18. This bioreporter responded to the alkanes in about 30 min and it was
      independent to the cell growth phase because of two point mutations in alkM
      promoter recognized by alkane regulatory protein ALKR. ADPWH_alk was applied to
      detect mineral oil, Brent, Chestnut and Sirri crude oils in water and seawater in
      the range 0.1-100 mg l(-1), showing that the bioreporter oil detection was semi
      quantitative. This study demonstrates that ADPWH_alk is a rapid, sensitive and
      semi-quantitative bioreporter that can be useful for environmental monitoring and
      assessment of oil spills in seawater and soils.

PMID- 21951421
TI  - A preliminary study of Salmonella, verocytotoxigenic Escherichia coli/Escherichia
      coli O157 and Campylobacter on four mixed farms.
AB  - The aims of this study were to investigate the incidence of Salmonella,
      verocytotoxigenic Escherichia coli (VTEC)/Escherichia coli O157 and Campylobacter
      on four mixed farms and to characterize the isolates in terms of a range of
      virulence factors. Eighty-nine composite (five different samples from the same
      animal species combined) faecal [cattle (24), pigs (14), sheep (4), poultry (4),
      horses (7), deer (4), dogs (9), rodents (2) and wild birds (20)] samples, 16
      composite soil samples plus 35 individual water samples were screened using
      culture-based, immunomagnetic separation and molecular methods. Salmonella was
      detected in bovine faeces, cattle and poultry house water. Salmonella
      serotypes/phage types included Dublin, Kiel and Typhimurium DT193, and most
      isolates were spvC, invA and rck positive. The pefA and rck genes were found
      exclusively in the non-Typhimurium strains, while Salmonella Dublin and
      Salmonella Kiel strains carried Salmonella genomic island I marker(s). VTEC/E.
      coli O157 were found in deer and dog faeces only. The E. coli O157 isolate was an
      enteroinvasive E. coli, while the VTEC isolate was untypable but carried the vt1,
      eaeA, hlyA, tir and eptD genes. This article reports the first confirmed carriage
      of E. coli O157 in Irish deer. Campylobacter species were not detected over the
      course of this study. It was concluded that [1] Salmonella, VTEC and
      Campylobacter have low (<5%) prevalence or are absent on the farms in this study;
      [2] water was an important source of bacterial pathogens; [3] both dogs and deer
      may act as a source of pathogenic E. coli and [4] key virulence and resistance
      determinants are widespread in farm Salmonella strains. This study highlights the
      need to control water as a source of pathogens and suggests that the domestic
      pets and deer should be considered in any farm risk assessment.

PMID- 21951422
TI  - Physical activity for obese individuals: a systematic review of effects on
      chronic disease risk factors.
AB  - The purpose of this review was to determine the effectiveness of physical
      activity in improving chronic disease risk factors in obese individuals. A
      systematic review was conducted to identify randomized physical activity
      intervention studies reporting changes in risk factors among obese individuals
      published prior to March 2010. Studies included in the review were randomized
      trials of at least 10 weeks in duration, with a sample mean body mass index >= 30
      kg/m(2) at baseline, and reporting a relevant risk factor (blood pressure, blood
      lipids, glucose/insulin or C-reactive protein). Forty-four studies met the
      inclusion criteria for this review. Overall, physical activity had no more than a
      modest effect on chronic disease risk factors in obese individuals. There was
      great heterogeneity in responses of risk factors across studies. In many studies
      it was difficult to determine the effect of physical activity, independent of
      changes in body mass consequent to the intervention. Obese individuals should be
      encouraged to undertake physical activity following general recommendations for
      weight loss and health. The degree to which physical activity is effective at
      lowering risk factor levels among high-risk obese individuals is not known.

PMID- 21951423
TI  - Therapeutic effects of ezetimibe for non-alcoholic steatohepatitis in fatty liver
      shionogi-ob/ob mice.
AB  - AIM:   An effective therapy for non-alcoholic steatohepatitis has yet to be
      defined. This study examined the therapeutic effects of ezetimibe, a lipid
      lowering medication, on steatosis and hepatic fibrosis in fatty liver Shionogi
      ob/ob (FLS-ob) mice. METHODS:   Low-dose (0.2 mg/kg body weight) and high-dose
      (1.0 mg/kg body weight) of ezetimibe were administered to FLS-ob mice orally for
      12 weeks. RESULTS:   Administration of ezetimibe significantly and dose
      dependently decreased liver cholesterol content. The area of hepatic fibrosis and
      hepatic hydroxyproline content in the low- and high-dose groups were
      significantly decreased compared with controls. Areas of alpha-smooth muscle
      actin positivity and F4/80 positivity were significantly decreased in a dose
      dependent manner. Percentages of 8-hydroxy-2-deoxyguanosine-positive cells in low
      and high-dose groups were significantly decreased compared with those in
      controls, and 8-hydroxy-2-deoxyguanosine DNA content and thiobarbituric acid
      reactive substances in the high-dose group was also significantly decreased
      compared to controls. Gene expression levels of procollagen I and transforming
      growth factor beta1 mRNA levels were lower in the low- and high-dose groups than
      in controls. Tumor necrosis factor-alpha and sterol regulatory element-binding
      protein 1c mRNA levels were also lower in the low- and high-dose groups than in
      controls. CONCLUSIONS:   Ezetimibe attenuated steatosis and liver fibrosis by
      reducing oxidative stress and lipid peroxidation and suppressing activated
      hepatic stellate cells and Kupffer cells.

PMID- 21951424
TI  - Expression of stromal-cell-derived factor-1 (SDF-1): a predictor of ischaemic
      stroke?
AB  - BACKGROUND AND PURPOSE: Platelet stromal-cell-derived factor-1 (SDF-1) plays a
      pivotal role in angiogenesis and the regeneration of ischaemic tissue through the
      regulation of haematopoietic progenitor cells and is upregulated at the sites of
      vascular injury and platelet activation. Thus, SDF-1 has recently been discussed
      as a predictor in ischaemic diseases such as acute myocardial infarction.
      However, no clinical data pertinent to the investigation of the platelet SDF-1
      expression in patients with stroke are available. METHODS: We consecutively
      evaluated 196 patients who were admitted to the stroke unit with symptoms
      suspected for stroke. Surface expression of the platelet activation markers (P
      selectin and GPIb) and the expression of platelet-bound SDF-1 were determined by
      two-colour whole blood flow cytometry. RESULTS: Patients with transient ischaemic
      attack (TIA) as well as with ischaemic stroke showed similar levels of SDF-1
      expression on hospital admission compared with patients with non-ischaemic (NI)
      events and with 30 healthy controls (TIA (mean fluorescence intensity+/-SD):
      31.5+/-18.2 vs. NI: 26.4+/-15.7; P=0.361; stroke: 28.7+/-19.8 vs. NI; P=0.943;
      control: 26.1+/-11.3; P>0.05 compared with all). Platelet SDF-1 expression showed
      a trend with the severity of stroke according to National Institute of Health
      Stroke Scale score (r=0.125; P=0.085), but significantly correlated with the peak
      levels of C-reactive protein (r=0.218; P=0.002) and with the levels of platelet
      activation (P-selectin: r=0.389; P=0.001). Multifactorial analysis of covariance
      revealed a significant influence on platelet SDF-1 expression by smoking
      (P=0.019). CONCLUSIONS: Platelet SDF-1 surface expression did not show any
      significant difference in patients with TIA and ischaemic stroke compared with
      patients with NI events. Thus, single biomarker evaluation of platelet SDF-1
      surface expression is not helpful to predict ischaemic stroke.

PMID- 21951425
TI  - New therapeutic targets for the treatment of erectile dysfunction.
AB  - INTRODUCTION: Despite the high efficacy and safety rates of the currently
      available treatments for erectile dysfunction, basic research reveals numerous
      new targets that are explored for therapeutic use. AIM: To overview potential new
      targets and to review available animal and human studies focusing on the
      potential of these targets for effective therapy for treating erectile
      dysfunction. METHODS: A comprehensive literature search was conducted using the
      PubMed and Medline database, and citations were selected based on relevance. MAIN
      OUTCOME MEASURES: Data are presented based on the analysis of the selected
      scientific information and published clinical trials. RESULTS: Fundamental
      research has, in the past decade, increased the understanding in both the
      physiological and the pathophysiological pathways that play a role in erectile
      function. As this information increases each day, new targets to treat erectile
      dysfunction are frequently presented. Currently a number of new therapeutic
      targets have been published. Some of them target the nitric oxide/cyclic
      guanosine monophosphate relaxation pathway as the phosphodiesterase type 5
      inhibitors do, others primarily target pathways involved in contraction. Also,
      targets within the central nervous system currently receive much attention. Some
      of these targets have already been used in clinical trials to test their efficacy
      and safety, with either disappointing or promising results. CONCLUSIONS: This
      review overviews potential therapeutic targets and summarizes animal as well as
      human studies evaluating their perspectives for the treatment of erectile
      dysfunction.

PMID- 21951433
TI  - Mindful "Vitality in Practice": an intervention to improve the work engagement
      and energy balance among workers; the development and design of the randomised
      controlled trial.
AB  - BACKGROUND: Modern working life has become more mental and less physical in
      nature, contributing to impaired mental health and a disturbed energy balance.
      This may result in mental health problems and overweight. Both are significant
      threats to the health of workers and thus also a financial burden for society,
      including employers. Targeting work engagement and energy balance could prevent
      impaired mental health and overweight, respectively. METHODS/DESIGN: The study
      population consists of highly educated workers in two Dutch research institutes.
      The intervention was systematically developed, based on the Intervention Mapping
      (IM) protocol, involving workers and management in the process. The workers'
      needs were assessed by combining the results of interviews, focus group
      discussions and a questionnaire with available literature. Suitable methods and
      strategies were selected resulting in an intervention including: eight weeks of
      customized mindfulness training, followed by eight sessions of e-coaching and
      supporting elements, such as providing fruit and snack vegetables at the
      workplace, lunch walking routes, and a buddy system. The effects of the
      intervention will be evaluated in a RCT, with measurements at baseline, six
      months (T1) and 12 months (T2). In addition, cost-effectiveness and process of
      the intervention will also be evaluated. DISCUSSION: At baseline the level of
      work engagement of the sample was "average". Of the study population, 60.1% did
      not engage in vigorous physical activity at all. An average working day consists
      of eight sedentary hours. For the Phase II RCT, there were no significant
      differences between the intervention and the control group at baseline, except
      for vigorous physical activity. The baseline characteristics of the study
      population were congruent with the results of the needs assessment. The IM
      protocol used for the systematic development of the intervention produced an
      appropriate intervention to test in the planned RCT. TRIAL REGISTRATION NUMBER:
      Netherlands Trial Register (NTR): NTR2199.

PMID- 21951435
TI  - An introduction.

PMID- 21951434
TI  - Safe use of oral isotretinoin after pseudo-tumor cerebri due to minocycline.

PMID- 21951436
TI  - Managing ethically questionable parental requests: growth suppression and
      manipulation of puberty.
AB  - Doctors sometimes struggle with ethically challenging requests for treatment from
      children's parents. For instance, we have recently had two requests by parents of
      children, a girl and a boy, each with a severe developmental disability, for
      hormonal therapy to suppress growth and puberty: the girl's parents requested, in
      addition, hysterectomy and mastectomy. We propose a reliable approach to
      assessing the ethical and legal aspects of these and other requests for 'non
      therapeutic' treatment of a minor who lacks the capacity to give informed
      consent. We argue that a doctor should first assess whether the request is one
      that he or she can, in conscience, accede to, and then, if it is, seek the
      authorisation of a court. We outline considerations relevant to the doctor's
      assessment of both the ethical issues and to the need for court authorisation.

PMID- 21951437
TI  - Improved neonatal survival and outcomes at borderline viability brings increasing
      ethical dilemmas.
AB  - With improvements in neonatal intensive care over the past five decades, the
      limits of viability have reduced to around 24 weeks' gestation. While increasing
      survival has been the predominant driver leading to lowering the gestation at
      which care can be provided, these infants remain at significant risk of adverse
      long-term outcomes including neuro-developmental disability. Decisions about
      commencing and continuing intensive care are determined in partnership with
      parents, considering the best interests of the baby and the family. Occasionally,
      clinicians and parents come to an impasse regarding institution or continuation
      of intensive care. Inevitably, these ethical dilemmas need to consider the
      uncertainty of the long-term prognosis and challenges surrounding providing or
      withdrawing active treatment. Further reduction in the gestational age considered
      for institution of intensive care will need to be guided by short- and long-term
      outcomes, community expectations and the availability of sufficient resources to
      care for these infants in the neonatal intensive care unit and beyond.

PMID- 21951438
TI  - Expressing ethical principles of treatment and care in a charter: what value?
AB  - More than ever before, public institutions are expected to have accessible
      guidelines on what they do, both for their staff and for those served by them.
      With this in mind, some principles of treatment and care of sick children were
      drafted for the Children's Hospital at Westmead. These were centred on ethics,
      primarily of what was best for the child. They were neither all-inclusive nor
      specific. They were labelled as a charter. They were rejected by a parent
      committee and met with unenthusiastic responses at meetings of hospital and
      ethics professionals. Reasons for this are unclear, but it is speculated that
      fear of the unknown and distrust of institutions may be factors. To date, the
      charter has not proved useful, except in provoking further discussion on how
      general guidelines are written, used and valued and on end-of-life decision
      making more generally.

PMID- 21951439
TI  - Ethics at the end of life: who should make decisions about treatment limitation
      for young children with life-threatening or life-limiting conditions?
AB  - It is now ethical orthodoxy that parents should be involved in the decision
      making about their children's health care. This extends to decisions about
      whether to continue or to limit life-sustaining medical treatment for a child
      with a life-limiting or life-threatening condition. What remains contested and
      uncertain is the extent and nature of parental involvement, especially in this
      emotionally charged situation. In particular, should it be the parents, who are
      the ultimate decision-makers, taking final responsibility, should it be a shared
      decision, or should it be a medical decision that parents are simply asked to
      consent to? One approach to this issue is to consider the in-principle ethical
      arguments and weigh their merits. The two key principles here are parental rights
      and authority, and the best interests of child, and the contested issue is what
      to do if these appear to clash. Another approach is to consider the principles in
      the practical clinical context. What would be the implications and consequences
      of adopting the model of parents as final decision-makers? Are parents able to
      carry out this role, and do they really want it? What is the effect on parents of
      taking this role? Answers to these questions could modify the in-principle
      ethical position. In this paper, we review the empirical evidence currently
      available on these questions, in relation to parents of infants and young
      children. Overall, the literature suggests that parents do want to be involved
      and do not suffer adverse psychological consequences from their involvement.
      However, the crucial ethical implication of the evidence is that the level and
      nature of parental involvement in decision-making should be negotiated with the
      parents in each case, because parents have a range of different views about
      taking final responsibility for decisions.

PMID- 21951440
TI  - Ethical considerations in paediatric neurology: neuromuscular disease and
      epilepsy.
AB  - The pace of developing technology with respect to many diagnostic tests, as well
      as available treatments including artificial ventilation, may have progressed at
      a faster rate than our ethical, humane ability to decide on the optimal choices
      for our patients. In fact, who should make these choices; physicians or patients
      and families? Certain ethical aspects of neuromuscular disorders and epilepsy are
      reviewed. For neuromuscular disease, the example of Duchenne muscular dystrophy
      (DMD) with regards to genetic testing, relatively early wheelchair placement and
      individualised invasive ventilation is discussed. In epilepsy, performing
      neurosurgery in severely impaired children is probably appropriate in some cases
      if desired by the family. Financial and human costs restrict therapies and
      testing for epilepsy as well as other neurological and medical diseases. Whether
      it is ethical to consider costs in medical treatment or not, it is certainly a
      reality.

PMID- 21951441
TI  - Consent and public engagement in an era of expanded childhood immunisation.
AB  - Childhood immunisation programmes have seen well-heralded successes in disease
      control. An increasing number of scheduled vaccines, narrowing risk-benefit
      ratios and public attention to vaccine safety raise new questions about consent.
      We first explore the challenges that this highly dynamic environment poses for
      valid consent. Then, we broaden this discussion to wider public engagement by
      suggesting how the public - the bearers of vaccine risk and benefit - can be
      better involved in immunisation policy.

PMID- 21951442
TI  - Too big to swallow.
AB  - The failure of current treatment approaches to severe obesity has resulted in
      significant investment by the scientific community to develop new treatments for
      this challenging health problem. Any new treatment must be scientifically tested
      to determine its potential role and any innovation in healthcare can be
      associated with moral and ethical challenges. This reflective piece is based on
      the experience of running the first randomised controlled trial to compare
      laparoscopic adjustable gastric banding to an intensive behaviourally-based
      intervention in adolescents with severe obesity during which many moral and
      ethical concerns were articulated by other health professionals. Five different
      types of responses are described (preventers, druggies, deferrers, slippery
      slopers and simplifiers). While raising important concerns, these responses also
      deflect attention from the urgent need to develop and test new treatments for the
      most severely obese adolescents. The stigma of obesity is posed as an underlying
      yet unaddressed issue.

PMID- 21951443
TI  - Gynaecological issues in adolescents with disability.
AB  - Menstruation and contraception is a concern for families who have a daughter with
      a significant disability, either physical or developmental. Accessing information
      regarding options may be difficult. Maternal experiences of menses further impact
      on the anxiety. The onset of menses is a reminder that their daughter is at risk
      of sexual abuse and pregnancy. It may highlight the fact that they are at their
      limits of coping - without the addition of yet another problem, of managing
      menses. Parental and carer concern is about the practicalities of how the
      adolescent will manage menstruation - both the hygiene aspects of menses and also
      the potential pain. Additionally, information is required about the possible need
      for contraception and the role and importance of reproductive hormones for
      preventing cardiac disease and osteoporosis. Recognition that a number of other
      medical problems may be related to reproductive hormones - such as cyclic
      seizure, behavioural difficulties and osteoporosis - is important as this gives
      an alternative avenue for intervention. The focus of this paper will be on the
      gynaecological aspects of young women with significant disabilities, rather than
      those with mild disabilities.

PMID- 21951444
TI  - Ethical issues in bone marrow transplantation in children.
AB  - In the 50 years since the first successful human bone marrow transplant (BMT) was
      performed in 1959, BMT has become the optimal therapy for a wide variety of life
      threatening paediatric haematological, immunological and genetic disorders.
      Unfortunately, while BMT generally provides the only possibility of cure for such
      afflicted children, few (25%) have a matched sibling available, and suitably
      matched unrelated donors are often not identified for many children in need of
      BMT. And even where BMT is possible, treatment is complex and arduous and
      associated with significant mortality and morbidity. The issues raised when
      either or both the donor and recipient are children and lack the capacity to make
      informed and rational decisions relating to BMT pose great challenges for all
      involved. This paper examines some of the ethical dilemmas that confront
      patients, families and medical practitioners when considering bone marrow
      transplantation in a child.

PMID- 21951445
TI  - Ethics, law and paediatric medicine.
AB  - Medicine is practised within an ethical and a legal framework. Doctors must
      obtain the broad consent of their patients before treatment begins, and tell them
      of their choices and the material risks inherent in treatment. Where children are
      the patients, it is their parents or guardians who must give their consent,
      unless the situation is an emergency or the children have been removed from
      parental custody and care. Today, mature teenagers may consent to their own
      medical treatment. Doctors must protect their patients' confidential information,
      however acquired. There are very limited exceptions where confidential
      information may be revealed, and a few where revelation is mandatory. Effective
      communication between doctors and their patients, or their parents, is of signal
      importance.

PMID- 21951446
TI  - Bad, mad and sad: rethinking the human condition in childhood with special
      relevance to moral development.
AB  - Identifying the territory, between what is subject to change and what is not in
      human functioning, is an extremely important strategy for limiting the range in
      which wisdom (discretion, judgment and the management of uncertainty) must be
      exercised. Over the last 30 years, child and adolescent psychiatry has seen an
      immense shift from the 'cannot change' category to the 'change category' and an
      even bigger shift to the territory between changeable and unchangeable. The
      question of the capacity for change in humans and the more traditional notion of
      'the human condition' are in need of re-evaluation. The possibility that there
      might be elements of the human condition that are beyond good and evil is
      especially relevant to the psychiatric treatment of children and young people.
      The notion of the human condition in children and adolescents becomes problematic
      if an essential element of the human condition is the irreducibly unchangeable,
      as the essence of youth is change and the capacity to change. The notion of
      personality disorder, and the persistence of disturbed behaviour that the
      diagnosis implies, are completely out of place in childhood and adolescence.
      There is a telling discrepancy between the small number of mental health
      treatment facilities and the large number of juvenile detention facilities in
      Australia. The problem is that we can achieve change, and there is little
      political or community will to enable it to happen.

PMID- 21951447
TI  - Parents know best: or do they? Treatment refusals in paediatric oncology.
AB  - Although treatment refusal is an infrequent occurrence in paediatric oncology, it
      is an important issue that threatens the ongoing therapeutic relationship between
      the health-care team and families. While there are good reasons to support the
      decision-making authority of parents in the medical setting, parents' rights in
      this respect are not absolute. Fortunately, most disagreements between clinicians
      and parents regarding treatment decisions for children are resolved within the
      health-care team/family dyad or with the objective advice of other clinicians or
      clinical ethics services. The increasing appeal of 'natural therapies' and
      unsubstantiated confidence with which they are prescribed may lead to more
      frequent refusal of conventional, evidence-based oncology treatment in the
      future. The harm principle may assist paediatric oncologists in the difficult
      task of determining when it is justifiable to refer a case for judicial
      intervention.

PMID- 21951448
TI  - Role and function of a paediatric clinical ethics service: experiences at the
      Royal Children's Hospital, Melbourne.
AB  - This article explores and analyses the role and functions of a clinical ethics
      service in paediatrics. It is based on the experiences of developing ethics
      capacity at the Royal Children's Hospital, Melbourne, which has evolved since
      2002 from a multidisciplinary advisory panel into Australia's first dedicated
      paediatric Children's Bioethics Centre, which opened in 2008. The ultimate goal
      is building ethics capacity and literacy across the hospital and continuing to
      support clinical staff managing patients and their families in ethically
      problematic cases. This is achieved through current case consultation, education
      and training, research and institutional policy, and guideline development. The
      experience of building a clinical ethics service has led to many changes to its
      structure over the years, with issues like timeliness of meeting, constitution of
      the group and referral and reporting structures arising as key elements of
      evolution. Challenges include resourcing and structure, institutional support,
      and family involvement in ethics consultations.

PMID- 21951449
TI  - Organ donation in Australia.
AB  - Organ donation in Australia has undergone a series of important changes in the
      past 3 years. An ethically complex and emotionally profound subject, important
      questions are being raised about the approach to organ donation by the
      government, by health-care professionals and also by the public. This paper
      highlights some of the changes within the Australian organ donation community and
      explores several controversies that accompany the widespread implementation of
      measures aimed at significantly improving organ donation throughout the country.

PMID- 21951450
TI  - Ethical advocacy based on caring: a model for neonatal and paediatric nurses.
AB  - Advocacy has been identified as an ideal in nursing practice. National codes
      (Australian Nursing and Midwifery Council) and professional standards (Australian
      College of Neonatal Nurses) state that nurses are to respect their patients'
      autonomous choices and act as their advocates. This responsibility includes
      acting as advocates for the needs and welfare of patients, for the profession of
      nursing and for the interests of colleagues in nursing. However, ambiguous
      interpretations of the concept of patient advocacy continue to pose a number of
      problems for nurses in practice and in particular neonatal practice. Neonatal
      nurses often perceive themselves primarily as advocates for the rights of
      helpless and vulnerable infants in their care. Advocacy is underpinned by caring,
      which is a significant feature in the delivery of quality care for each baby and
      child. This advocacy may be expressed at the bedside, in committee meetings, in
      agency discussions or in the public arena.

PMID- 21951451
TI  - Science and ethics of human immunodeficiency virus/acquired immunodeficiency
      syndrome controversies in Africa.
AB  - The human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS)
      epidemic in Africa has raised important ethical issues for both researchers and
      clinicians. The most notorious controversy has been related to the zidovudine
      (AZT) trials in Africa in the late 1990s, in which the control groups were given
      a placebo rather than an effective drug to prevent vertical transmission. This
      raised concerns in the sponsoring country about exploitation of subjects,
      injustice and an ethical double standard between donor countries and resource
      poor settings. However, the real double standard is between clinical practice
      standards in Western versus African countries, which must be addressed as part of
      the increasing global inequity of wealth both between countries and also within
      countries. There are important limitations to ethical declarations, principles
      and guidelines on their own without contextual ethical reasoning. The focus on
      research ethics with the HIV epidemic has led to a relative neglect of ethical
      issues in clinical practice. Although the scientific advances in HIV/AIDS have
      changed the ethical issues since the 1990s, there has also been progress in the
      bioethics of HIV/AIDS in terms of ethical review capability by local committees
      as well as in exposure to ethical issues by clinicians and researchers in Africa.
      However, serious concerns remain about the overregulation of research by
      bureaucratic agencies which could discourage African research on specifically
      African health issues. There is also a need for African academic institutions and
      researchers to progressively improve their research capacity with the assistance
      of research funders and donor agencies.

PMID- 21951452
TI  - Going against the grain: Liam's story.
AB  - You might well say, 'Why would you want to write about your son's death?' And in
      response I may ask, 'Why do you want to read it?' Perhaps there are no correct
      answers to our questions, except to say that the only way we learn it, ethically,
      through the experiences of others as we witness their suffering. Although, for
      the most part, this journey would leave me feeling professionally abandoned,
      there were still times of joy, hope and love. I invite you to take this journey
      with me.

PMID- 21951453
TI  - Commentary on "going against the grain: Liam's story".

PMID- 21951454
TI  - Ethical and legal aspects of management for disorders of sex development.
AB  - Intense controversy surrounds the management of disorders of sex development,
      particularly in relation to the validity of parental consent for genital surgery
      and the removal of gonadal tissue carried out during infancy or childhood. Past
      practices have been heavily criticised on ethical grounds by patient advocacy
      organisations, who have demanded a moratorium on these kinds of operations unless
      authorised by a court. Some doctors and hospital administrators have been
      influenced by the controversy and have referred cases to the Family Court of
      Australia, where a series of judgements have now established legal precedents
      that apply across Australia, restricting the circumstances in which parents can
      give consent for surgery. An alternative approach is to use a hospital-based
      Clinical Ethics Response Group and, if necessary, Clinical Ethics Committee,
      which has lay and legal representatives as well as health professionals, as a
      semi-independent committee of review. Finding a solution that protects the human
      rights and best interests of children is an ongoing challenge.

PMID- 21951455
TI  - The ethics of paediatric research.
AB  - Paediatric research is essential for improving health outcomes of children.
      Waiting for adult studies before conducting paediatric studies will prolong the
      denial of effective treatment for children. If we rely on information from adult
      studies rather than conducting studies with children, we risk causing harm to
      children. In this paper, we identify and examine ethical issues unique to
      conducting research with children. These include the function and the value of a
      child's assent and the criteria that should guide a proxy in making decisions
      about a child's involvement in research, offering payment to children for
      research participation and acceptable levels of risk for paediatric research.
      Justice demands that children not be denied the benefits of research, and it is
      the role of the paediatric medical community to advocate not only for more
      research for children but also to ensure that the research conducted is of the
      highest quality.

PMID- 21951456
TI  - Ethical issues in genetics.
AB  - Genetic disorders are caused by abnormalities in genes and chromosomes and for
      the most part have implications for family members, affecting such matters as
      confidentiality and disclosure to third parties. Genetic testing can be not only
      diagnostic but also predictive, raising issues of the need for pre-test
      counselling, protection of children from unwanted testing, and most importantly,
      the imprecision of interpretation of future risk. The rise in availability of
      direct-to-consumer testing is a fresh cause for concern, as are the new
      possibilities in reproductive medicine. New technologies and the falling cost of
      whole genome sequencing ensure that ethics will be a prominent concern for
      clinical genetics.

PMID- 21951457
TI  - Stem cells: research tools and clinical treatments.
AB  - The term 'stem cell' most commonly refers to embryonic stem cells, particularly
      in the lay media; however, it also describes other cell types. A stem cell
      represents a cell of multi-lineage potential with the ability for self-renewal.
      It is now clear that the plasticity and immortality of a given stem cell will
      depend on what type of stem cell it is, whether an embryonic stem cell, a fetal
      placental stem cell or an adult stem cell. Stem cells offer great promise as cell
      based therapies for the future. With evolving technology, much of the socio
      political debate regarding stem cells can now be avoided.

PMID- 21951459
TI  - Letter to the editor.

PMID- 21951461
TI  - Publishing operational research from 'real life' programme data: a better form of
      accountability.
AB  - Publishing in peer-reviewed journals especially from programme work remains very
      limited in low-income countries, and several arguments have been advanced to
      change this situation. In this viewpoint, we propose an additional argument for
      publishing operational research from programmes as a better form of
      accountability. We urge in this article that for those involved in programme
      design, implementation, monitoring and evaluation including donors, if you do not
      publish articles from your programme or research project, you have not accounted
      well enough.

PMID- 21951462
TI  - Remission of alopecia universalis following successful clinical islet
      transplantation.

PMID- 21951463
TI  - A highly sensitive novel PCR assay for detection of Pneumocystis jirovecii DNA in
      bronchoalveloar lavage specimens from immunocompromised patients.
AB  - Pneumocystis jirovecii pneumonia (PCP) is a leading cause of morbidity and
      mortality in immunocompromised patients. Despite the sensitivity of the commonly
      used PCR for diagnosing P. jirovecii with primers pAZ102-H/pAZ102-E and pAZ102
      X/pAZ102-Y derived from mtLSU rRNA (conventional PCR), some PCP patients who had
      demonstrable organisms by staining methods failed to give positive PCR results.
      Herein, we devised a more sensitive PCR assay derived from the same gene target
      to circumvent these false-negative tests. Single brochoalveolar lavage (BAL)
      samples were collected from human immunodeficiency virus (HIV)-infected (n = 66)
      and non-HIV (n = 36) immunocompromised patients presenting with fever, dyspnoea,
      cough and pulmonary infiltrates. Pneumocystis jirovecii was diagnosed with Giemsa
      stained smear, immunofluorescence assay, conventional single-round and nested
      PCR, and new single-round and nested PCR in 46 (45.1%), 53 (52.0%), 69 (67.6%),
      74 (72.6%), 87 (85.3%) and 91 (89.2%) patients, respectively. The new PCR could
      detect P. jirovecii DNA in BAL fluids two to three orders of magnitude more
      dilute than conventional PCR. Sequence analysis revealed one to three nucleotide
      substitutions within the primers for conventional PCR among clinical isolates.
      Although both conventional and new PCR assays were highly specific for diagnosing
      P. jirovecii, the new PCR yielded more positive results than conventional PCR
      among BAL samples that were negative by both Giemsa stain and immunofluorescence
      assay. Hence, the new PCR offered a more sensitive detection of P. jirovecii
      infection and colonization than conventional PCR.

PMID- 21951464
TI  - Implant overdentures and nutrition: a randomized controlled trial.
AB  - We conducted a randomized clinical trial to determine whether providing simple
      mandibular implant overdentures (IODs) to elderly individuals would give them a
      significantly better nutritional profile than those who receive complete dentures
      (CDs). Two hundred fifty-five edentate patients > 65 yrs were randomly assigned
      to receive maxillary CDs and mandibular IODs (n = 128) or CDs (n = 127). Six
      month and one-year post-treatment outcomes were blood plasma levels of
      homocysteine (tHcy), vitamin B12, vitamin B6, albumin, serum folate, and C
      reactive protein concentrations, as well as dietary intake. The association
      between treatment and tHcy levels was not statistically significant. A decline of
      folate from baseline values in both study groups, as well as those of vitamins B6
      and B12 and albumin, was observed. Significant between-group differences were
      detected in food preparation and in the individuals' ability to chew a variety of
      foods. This study suggests that implant overdentures do not have a more positive
      effect on the nutritional state of elderly edentate individuals at 6 and 12 mos
      post-treatment than new complete dentures. However, those wearing IODs are
      significantly more likely to take in their nutrients through fresh, whole fruits
      and vegetables.

PMID- 21951465
TI  - Nuclear dynamics during plant innate immunity.

PMID- 21951466
TI  - Transcriptome response to embolism formation in stems of Populus trichocarpa
      provides insight into signaling and the biology of refilling.
AB  - The mechanism of embolism repair in transpiring plants is still not understood,
      despite significant scientific effort. The refilling process is crucial to
      maintaining stem transport capacity and ensuring survival for plants experiencing
      dynamic changes in water stress. Refilling air-filled xylem vessels requires an
      energy and water source that can only be provided by adjacent living parenchyma
      cells. Here, we report an analysis of the transcriptome response of xylem
      parenchyma cells after embolism formation in Populus trichocarpa trees. Genes
      encoding aquaporins, ion transporters, and carbohydrate metabolic pathways were
      up-regulated, and there was a significant reduction in the expression of genes
      responding to oxidative stress. Thus, a novel view of the plant response to
      embolism emerges that suggests a role for oxygen in embolized vessels as a signal
      triggering xylem refilling and for the activity of cation transport as having a
      significant role in the generation of the energy gradient necessary to heal
      embolized vessels. These findings redefine current hypotheses surrounding the
      refilling phenomenon and provide insight into the complexity of the biological
      response to the seemingly simple physical event of xylem embolism formation.

PMID- 21951467
TI  - Genome-wide direct target analysis reveals a role for SHORT-ROOT in root vascular
      patterning through cytokinin homeostasis.
AB  - SHORT-ROOT (SHR) is a key regulator of root growth and development in Arabidopsis
      (Arabidopsis thaliana). Made in the stele, the SHR protein moves into an adjacent
      cell layer, where it specifies endodermal cell fate; it is also essential for
      apical meristem maintenance, ground tissue patterning, vascular differentiation,
      and lateral root formation. Much has been learned about the mechanism by which
      SHR controls radial patterning, but how it regulates other aspects of root
      morphogenesis is still unclear. To dissect the SHR developmental pathway, we have
      determined the genome-wide locations of SHR direct targets using a chromatin
      immunoprecipitation followed by microarray analysis method. K-means clustering
      analysis not only identified additional quiescent center-specific SHR targets but
      also revealed a direct role for SHR in gene regulation in the pericycle and
      xylem. Using cell type-specific markers, we showed that in shr, the phloem and
      the phloem-associated pericycle expanded, whereas the xylem and xylem-associated
      pericycle diminished. Interestingly, we found that cytokinin level was elevated
      in shr and that exogenous cytokinin conferred a shr-like vascular patterning
      phenotype in wild-type root. By chromatin immunoprecipitation-polymerase chain
      reaction and reverse transcription-polymerase chain reaction assays, we showed
      that SHR regulates cytokinin homeostasis by directly controlling the
      transcription of cytokinin oxidase 3, a cytokinin catabolism enzyme
      preferentially expressed in the stele. Finally, overexpression of a cytokinin
      oxidase in shr alleviated its vascular patterning defect. On the basis of these
      results, we suggest that one mechanism by which SHR controls vascular patterning
      is the regulation of cytokinin homeostasis.

PMID- 21951468
TI  - A new insight into application for barley chromosome addition lines of common
      wheat: achievement of stigmasterol accumulation.
AB  - Barley (Hordeum vulgare) has a much higher content of bioactive substances than
      wheat (Triticum aestivum). In order to investigate additive and/or synergistic
      effect(s) on the phytosterol content of barley chromosomes, we used a series of
      barley chromosome addition lines of common wheat that were produced by normal
      crossing. In determining the plant sterol levels in 2-week-old seedlings and dry
      seeds, we found that the level of stigmasterol in the barley chromosome 3
      addition (3H) line in the seedlings was 1.5-fold higher than that in the original
      wheat line and in the other barley chromosome addition lines, but not in the
      seeds. Simultaneously, we determined the overall expression pattern of genes
      related to plant sterol biosynthesis in the seedlings of wheat and each addition
      line to assess the relative expression of each gene in the sterol pathway. Since
      we elucidated the CYP710A8 (cytochrome P450 subfamily)-encoding sterol C-22
      desaturase as a key characteristic for the higher level of stigmasterol, full
      length cDNAs of wheat and barley CYP710A8 genes were isolated. These CYP710A8
      genes were mapped on chromosome 3 in barley (3H) and wheat (3A, 3B, and 3D), and
      the expression of CYP710A8 genes increased in the 3H addition line, indicating
      that it is responsible for stigmasterol accumulation. Overexpression of the
      CYP710A8 genes in Arabidopsis increased the stigmasterol content but did not
      alter the total sterol level. Our results provide new insight into the
      accumulation of bioactive compounds in common wheat and a new approach for
      assessing plant metabolism profiles.

PMID- 21951469
TI  - Photobodies in light signaling.

PMID- 21951470
TI  - Are parental concerns for child TV viewing associated with child TV viewing and
      the home sedentary environment?
AB  - BACKGROUND: Time spent watching television affects multiple aspects of child and
      adolescent health. Although a diverse range of factors have been found to be
      associated with young people's television viewing, parents and the home
      environment are particularly influential. However, little is known about whether
      parents, particularly those who are concerned about their child's television
      viewing habits, translate their concern into action by providing supportive home
      environments (e.g. rules restricting screen-time behaviours, limited access to
      screen-based media). The aim of this study was to examine associations between
      parental concerns for child television viewing and child television viewing and
      the home sedentary environment. METHODS: Parents of children aged 5-6 years
      ('younger' children, n = 430) and 10-12 years ('older children', n = 640)
      reported usual duration of their child's television (TV) viewing, their concerns
      regarding the amount of time their child spends watching TV, and on aspects of
      the home environment. Regression analyses examined associations between parental
      concern and child TV viewing, and between parental concern and aspects of the
      home environment. Analyses were stratified by age group. RESULTS: Children of
      concerned parents watched more TV than those whose parents were not concerned (B
      = 9.63, 95% CI = 1.58-17.68, p = 0.02 and B = 15.82, 95% CI = 8.85-22.80, p <
      0.01, for younger and older children respectively). Parental concern was
      positively associated with younger children eating dinner in front of the
      television, and with parental restriction of sedentary behaviours and offering
      sedentary activities (i.e. TV viewing or computer use) as a reward for good
      behaviour among older and young children. Furthermore, parents of older children
      who were concerned had fewer televisions in the home and a lower count of
      sedentary equipment in the home. CONCLUSIONS: Children of concerned parents
      watched more TV than those whose parents who were not concerned. Parents appear
      to recognise excessive television viewing in their children and these parents
      appear to engage in conflicting parental approaches despite these concerns.
      Interventions targeting concerned parents may be an innovative way of reaching
      children most in need of strategies to reduce their television viewing and
      harnessing this parental concern may offer considerable opportunity to change the
      family and home environment.

PMID- 21951471
TI  - Surgical treatment of giant plexiform neurofibroma associated with pectus
      excavatum.
AB  - Plexiform neurofibromas are benign tumors originating from subcutaneous or
      visceral peripheral nerves, which are usually associated with neurofibromatosis
      type 1. They are almost always congenital lesions and often cause the surrounding
      soft tissue and bone to grow aberrantly. We treated a 12-year-old boy who
      presented with asymmetric pectus excavaum and an anterior chest wall plexiform
      neurofibroma. The pectus excavaum was corrected by modified Nuss procedure,
      followed by simultaneous resection of the giant mass. The patient is doing well
      at the 4 years follow-up visit.

PMID- 21951472
TI  - The role of endoscopy in the management of choledocholithiasis.

PMID- 21951473
TI  - Complications of colonoscopy.

PMID- 21951474
TI  - Confocal laser endomicroscopy: finally ready to change clinical practice?

PMID- 21951475
TI  - Long-term outcomes of combination of endoscopic submucosal dissection and
      laparoscopic lymph node dissection without gastrectomy for early gastric cancer
      patients who have a potential risk of lymph node metastasis.
AB  - BACKGROUND: Our recently developed procedure, a combination of endoscopic
      submucosal dissection (ESD) and laparoscopic lymph node dissection (LLND), may
      lead to the elimination of unnecessary gastrectomy in early gastric cancer (EGC)
      patients having a potential risk of lymph node metastasis (LNM). OBJECTIVE: To
      examine the long-term outcomes of the combination of ESD and LLND. DESIGN: A
      retrospective study using consecutive data. SETTING: Single academic center.
      PATIENTS AND INTERVENTIONS: Twenty-one EGC patients having a potential risk of
      LNM were treated by ESD followed by LLND. MAIN OUTCOME MEASUREMENTS: Long-term
      outcomes of the combination of ESD and LLND. RESULTS: The histopathological
      examination of the dissected lymph nodes confirmed the absence of LNM in 19 of
      the 21 patients. Two patients who had LNM were followed without any additional
      surgery in accordance with the patients' wishes. During the median follow-up of
      61 months, all of the patients were alive without any recurrent disease. Two
      patients (10%) had symptoms such as abdominal distention and belching, which were
      associated with disturbed gastric emptying between meals. Endoscopic examination
      2 years postoperatively revealed food residue problems in 3 patients (15%).
      However, the preoperative quality of life was restored with no dietary
      restrictions, and body weight was well maintained in all of the patients.
      LIMITATIONS: A retrospective study with a small number of patients. CONCLUSIONS:
      The combination of ESD and LLND can be an effective, minimally invasive treatment
      that maintains long-term quality of life for selected EGC patients having a
      potential risk of LNM.

PMID- 21951476
TI  - Single-operator cholangioscopy in biliary disorders: going beyond visualization.

PMID- 21951477
TI  - The color of the most effective tool to use in dysplasia surveillance in
      inflammatory bowel disease.

PMID- 21951479
TI  - Advanced endoscopy procedures in private practice: is the juice worth the
      squeeze?

PMID- 21951478
TI  - Adverse events in older patients undergoing colonoscopy: a systematic review and
      meta-analysis.
AB  - BACKGROUND: Studies suggest that advancing age is an independent risk factor for
      experiencing adverse events during colonoscopy. Yet many of these studies are
      limited by small sample sizes and/or marked variation in reported outcomes.
      OBJECTIVE: To determine the incidence rates for specific adverse events in
      elderly patients undergoing colonoscopy and calculate incidence rate ratios for
      selected comparison groups. SETTING AND PATIENTS: Elderly patients undergoing
      colonoscopy. DESIGN: Systematic review and meta-analysis. MAIN OUTCOME
      MEASUREMENTS: Perforation, bleeding, cardiovascular (CV)/pulmonary complications,
      and mortality. RESULTS: Our literature search yielded 3328 articles, of which 20
      studies met our inclusion criteria. Pooled incidence rates for adverse events
      (per 1000 colonoscopies) in patients 65 years of age and older were 26.0 (95% CI,
      25.0-27.0) for cumulative GI adverse events, 1.0 (95% CI, 0.9-1.5) for
      perforation, 6.3 (95% CI, 5.7-7.0) for GI bleeding, 19.1 (95% CI, 18.0-20.3) for
      CV/pulmonary complications, and 1.0 (95% CI, 0.7-2.2) for mortality. Among
      octogenarians, adverse events (per 1000 colonoscopies) were as follows:
      cumulative GI adverse event rate of 34.9 (95% CI, 31.9-38.0), perforation rate of
      1.5 (95% CI, 1.1-1.9), GI bleeding rate of 2.4 (95% CI, 1.1-4.6), CV/pulmonary
      complication rate of 28.9 (95% CI, 26.2-31.8), and mortality rate of 0.5 (95% CI,
      0.06-1.9). Patients 80 years of age and older experienced higher rates of
      cumulative GI adverse events (incidence rate ratio 1.7; 95% CI, 1.5-1.9) and had
      a greater risk of perforation (incidence rate ratio 1.6, 95% CI, 1.2-2.1)
      compared with younger patients (younger than 80 years of age). There was an
      increased trend toward higher rates of GI bleeding and CV/pulmonary complications
      in octogenarians but neither was statistically significant. LIMITATIONS:
      Heterogeneity of studies included and not all complications related to
      colonoscopy were captured. CONCLUSIONS: Elderly patients, especially
      octogenarians, appear to have a higher risk of complications during and after
      colonoscopy. These data should inform clinical decision making, the consent
      process, public health policy, and comparative effectiveness analyses.

PMID- 21951480
TI  - Biliary stent migration with colonic perforation: a very rare complication and
      the lesson that should be learned from it.

PMID- 21951481
TI  - Tumor seeding after EUS-guided FNA of pancreatic tail neoplasia.

PMID- 21951482
TI  - Flexible spectral-imaging color enhancement: optimized settings for polyp
      detection?

PMID- 21951483
TI  - The Edinburgh experience with two small-bowel capsule endoscopy systems.

PMID- 21951485
TI  - Accelerated hypofractionated adjuvant whole breast radiotherapy with concomitant
      photon boost after conserving surgery for early stage breast cancer: a
      prospective evaluation on 463 patients.
AB  - The current standard therapeutic option for early stage breast cancer (EBC)
      employs a multimodality treatment approach including conservative surgery,
      radiotherapy, chemotherapy, and hormone therapy. The most common adjuvant
      radiotherapeutic strategy consists of external beam radiation therapy (EBRT)
      delivered to the whole breast using 1.8-2 Gy fractions given five times a week,
      up to a total dose of 45-50 Gy over a period of 5 weeks. In recent years, altered
      schedules employing larger dose per fraction delivered in fewer treatment
      sessions over a shorter overall treatment time began to be explored. We herein
      present clinical data on accelerated hypofractionated adjuvant whole-breast
      radiotherapy delivered on a daily basis for a total treatment time of 20
      fractions. Between February 2005 and June 2009, a total of 463 patients underwent
      hypofractionated accelerated adjuvant radiation after conservative surgery for
      early breast cancer (pathological stage pTis, pT1 or pT2, pN0-N1). The basic
      course of radiotherapy consisted of 45 Gy, to the whole breast in 20 fractions
      with 2.25 Gy/fraction; an additional daily boost dose of 0.25 Gy was
      concomitantly delivered, to the lumpectomy cavity, for an additional total dose
      of 5 Gy. The cumulative nominal dose was 50 Gy. At follow-up, patients were
      examined at 3 and 6 months after the end of radiotherapy and twice a year
      afterward. Toxicity was scored according to the Common Terminology Criteria for
      Adverse Events, using the Radiation Therapy Oncology Group /European Organization
      for Research and Treatment of Cancer toxicity scale. Cosmetic results were
      assessed in agreement with the Harvard criteria. All the 463 patients treated
      with the accelerated hypofractionated adjuvant whole-breast radiotherapy schedule
      achieved at least 6 months' follow-up and subsequently were considered for the
      present analysis. With a median follow-up of 27 months, 5-year DFS is 93.1%. Only
      three patients experienced disease recurrence: two of them with an axillary nodal
      relapse; one patient with systemic spread. No local relapse occurred. No major
      toxicities (grade 3 or more) were detected during follow-up. Only 2% of the
      patients experienced grade 3 skin toxicity at the very end of the radiotherapy
      course. Cosmetic result was assessed and scored at 6 months, 1 year, 2 years:
      100% of patients showed excellent or good cosmetic result. The explored
      accelerated hypofractionated adjuvant radiotherapeutic approach for early breast
      cancer with concomitant photon boost seems to be feasible providing consistent
      clinical results with excellent short-to-medium-term toxicity profile.

PMID- 21951487
TI  - Marine algal pinnatoxins E and F cause neuromuscular block in an in vitro
      hemidiaphragm preparation.
AB  - Members of the cyclic imine group of toxins, gymnodimine and spirolides, have
      been found to be potent antagonists of both muscle type and neuronal nicotinic
      acetylcholine receptors. These toxins exhibit fast acting toxicity in vivo,
      causing death within minutes by respiratory depression. This toxicity is shared
      by the novel cyclic imine pinnatoxins E and F, produced by marine dinoflagellates
      and recently isolated from New Zealand shellfish. However, there is currently
      very little data available regarding the mechanism of action for any of the
      pinnatoxins, and no data at all on the novel pinnatoxins E and F. The aim of the
      current study was to investigate potential antagonism of nicotinic acetylcholine
      receptors by pinnatoxins E and F using two in vitro tissue preparations. Compound
      muscle action potentials elicited by stimulation of the phrenic nerve were
      recorded from the hemidiaphragm in order to test effects on muscle type
      heteromeric nicotinic receptors, while effects on alpha7 homomeric neuronal
      nicotinic receptors were investigated by recording gamma oscillations in response
      to tetanic stimulation of the CA1 region of the hippocampus. Both a crude extract
      containing a mixture of pinnatoxins E and F, as well as pure pinnatoxin F, had no
      effect on gamma oscillation spectral density or spike count at any
      concentrations. Conversely, at these same concentrations, both crude and pure
      pinnatoxin caused an almost complete abolition of nerve-evoked hemidiaphragm
      action potential responses, without any effect on electrically-evoked (direct)
      responses. This neuromuscular block could not be reversed by neostigmine. These
      results show that pinnatoxins E and F block neuromuscular transmission and
      suggest that observed in vivo muscle paralysis by pinnatoxin is due to selective
      antagonism of muscle type nicotinic acetylcholine receptors.

PMID- 21951486
TI  - Population structure of the Yersinia pseudotuberculosis complex according to
      multilocus sequence typing.
AB  - Multilocus sequence analysis of 417 strains of Yersinia pseudotuberculosis
      revealed that it is a complex of four populations, three of which have been
      previously assigned species status [Y. pseudotuberculosis sensu stricto (s.s.),
      Yersinia pestis and Yersinia similis] and a fourth population, which we refer to
      as the Korean group, which may be in the process of speciation. We detected clear
      signs of recombination within Y. pseudotuberculosis s.s. as well as imports from
      Y. similis and the Korean group. The sources of genetic diversification within Y.
      pseudotuberculosis s.s. were approximately equally divided between recombination
      and mutation, whereas recombination has not yet been demonstrated in Y. pestis,
      which is also much more genetically monomorphic than is Y. pseudotuberculosis
      s.s. Most Y. pseudotuberculosis s.s. belong to a diffuse group of sequence types
      lacking clear population structure, although this species contains a melibiose
      negative clade that is present globally in domesticated animals. Yersinia 
      similis corresponds to the previously identified Y. pseudotuberculosis genetic
      type G4, which is probably not pathogenic because it lacks the virulence factors
      that are typical for Y. pseudotuberculosis s.s. In contrast, Y.
      pseudotuberculosis s.s., the Korean group and Y. pestis can all cause disease in
      humans.

PMID- 21951488
TI  - Contagious caprine pleuropneumonia: new aspects of an old disease.
AB  - Contagious caprine pleuropneumonia (CCPP), caused by Mycoplasma capricolum subsp.
      capripneumoniae, is a serious OIE-listed disease affecting goats in the Middle
      East, north and east Africa and Asia. Mortality and morbidity rates can be as
      high as 60% and 90%, respectively, when the disease first enters a territory,
      invariably through carrier animals. Recent detections of CCPP in Pakistan and
      Tajikistan are probably the result of improved diagnosis as the disease has been
      suspected there for many years, while those in Thrace in 2003 and Mauritius in
      2009 represent new outbreaks. CCPP was thought to be highly host specific until
      recent outbreaks in wildlife species including gazelles and gerenuks show that
      the causative mycoplasma has broader specificity. Diagnosis was hampered by the
      fastidiousness of the causative mycoplasma but molecular-based tests like PCR
      have greatly improved detection. Rapid latex agglutination tests that can be
      performed at the penside are also available for antibody detection. Clinically
      affected animals respond to a range of antibiotics although it is unlikely that
      this results in complete elimination of the mycoplasma. Vaccines consisting of
      saponized organisms have been shown to be protective but the quality and efficacy
      may be variable.

PMID- 21951489
TI  - Mass distribution and rotational inertia of "microtype" and "freely mobile"
      middle ear ossicles in rodents.
AB  - The middle ears of seven species of rodents, including four hamster species, were
      examined under light microscopy and through micro-CT imaging. Hamsters were found
      to possess a spectrum of ossicular morphologies ranging from something
      approaching "freely mobile" (Mesocricetus) to something nearer the "microtype"
      (Cricetulus), although no hamster has an orbicular apophysis of the malleus.
      Rats, mice and Calomyscus were found to have typically microtype ossicles. To
      explore the functional effects of these morphological differences, CT scan data
      were used to calculate the magnitudes of the moments of inertia and positions of
      the centres of mass and principal rotational axes for the malleus-incus
      complexes. Microtype species were found to have much greater ossicular inertias,
      relative to size, about the "anatomical axis" extending between anterior process
      of the malleus and short process of the incus; ossicular centres of mass were
      displaced further from this axis. Calculated inertial values were then put into
      an existing model of middle ear function (Hemila et al., 1995), in order to see
      whether the more accurate data would improve predictions of upper hearing limits.
      For the rat and mouse they did, but this was not so for the hamster Mesocricetus.
      This might indicate that the inner rather than the middle ear limits hearing in
      this species, or might simply reflect other shortcomings of the model. Functional
      differences appear to exist even among rodent ears of the same general type, but
      the adaptive significance of these differences remains enigmatic.

PMID- 21951490
TI  - The Lean method as a clinical pathway facilitator in patients with lung cancer.
AB  - INTRODUCTION: Patient flow during workup for lung cancer is often difficult to
      influence because of delay at many levels: patient delay, doctors' delay and
      waiting time for X-ray and CT scan, referral to specialist, and waiting time for
      chemotherapy and radiotherapy or surgery. A mean workup time of 4 months is not
      unusual. OBJECTIVES: To improve quality and shorten the workup time for patients
      with lung cancer. METHODS: It was decided to employ a program designed by the
      Toyota car industry, the Lean process, as a tool to improve workup time. A Lean
      process implicates all levels of an institution with project and focus groups
      having workshops to analyse present status and suggest improvements. RESULTS:
      Since introducing the Lean project, we have decreased the workup time from a mean
      of 64 days to 16 days, and the median time from diagnosis to surgery was reduced
      from 26.5 days to 15 days. CONCLUSION: It is feasible to improve patient flow for
      patients with lung cancer by employing the Lean method as a pathway instrument.

PMID- 21951492
TI  - Special issue: International reviews. Foreword.

PMID- 21951493
TI  - Editors' choice.

PMID- 21951494
TI  - Progress towards achieving Millennium Development Goal 5 in South-East Asia.

PMID- 21951495
TI  - To ensure maternal mortality is reduced, quality of care needs to be monitored
      and improved alongside increasing skilled delivery coverage rates.

PMID- 21951496
TI  - Better understanding of maternal deaths--the new WHO cause classification system.

PMID- 21951497
TI  - Unfolding the universe of newborn health interventions: the role of innovative
      community-based strategies.

PMID- 21951498
TI  - The role of the South Asia Federation of Obstetrics and Gynaecology (SAFOG) in
      South Asia.

PMID- 21951499
TI  - Reducing maternal mortality in Nepal.

PMID- 21951491
TI  - Speciation despite globally overlapping distributions in Penicillium chrysogenum:
      the population genetics of Alexander Fleming's lucky fungus.
AB  - Eighty years ago, Alexander Fleming described the antibiotic effects of a fungus
      that had contaminated his bacterial culture, kick starting the antimicrobial
      revolution. The fungus was later ascribed to a putatively globally distributed
      asexual species, Penicillium chrysogenum. Recently, the species has been shown to
      be genetically diverse, and possess mating-type genes. Here, phylogenetic and
      population genetic analyses show that this apparently ubiquitous fungus is
      actually composed of at least two genetically distinct species with only slight
      differences detected in physiology. We found each species in air and dust samples
      collected in and around St Mary's Hospital where Fleming worked. Genotyping of 30
      markers across the genome showed that preserved fungal material from Fleming's
      laboratory was nearly identical to derived strains currently in culture
      collections and in the same distinct species as a wild progenitor strain of
      current penicillin producing industrial strains rather than the type species P.
      chrysogenum. Global samples of the two most common species were found to possess
      mating-type genes in a near 1:1 ratio, and show evidence of recombination with
      little geographic population subdivision evident. However, no hybridization was
      detected between the species despite an estimated time of divergence of less than
      1MYA. Growth studies showed significant interspecific inhibition by P.
      chrysogenum of the other common species, suggesting that competition may
      facilitate species maintenance despite globally overlapping distributions.
      Results highlight under-recognized diversity even among the best-known fungal
      groups and the potential for speciation despite overlapping distribution.

PMID- 21951500
TI  - The role of family planning in South Asia.

PMID- 21951501
TI  - Achieving Millennium Development Goals 4 and 5 in Bangladesh.
AB  - Bangladesh has made commendable progress in achieving Millennium Development
      Goals (MDGs) 4 and 5. Since 1990, there has been a remarkable reduction in
      maternal and child mortality, with an estimated 57% reduction in child mortality
      and 66% in maternal mortality. This review highlights that, whereas Bangladesh is
      on track for achieving MDG 4 and 5A, progress in universal access to reproductive
      health (5B) is not yet at the required pace to achieve the targets set for 2015.
      In addition, Bangladesh needs to further enhance activities to improve newborn
      health and promote skilled attendance at birth.

PMID- 21951502
TI  - Achieving Millennium Development Goals 4 and 5 in India.
AB  - This review relates to achieving the Millennium Development Goals (MDGs),
      especially MDGs 4 and 5, by India by the year 2015. India contributes the maximum
      number of maternal deaths (68,000) to the global estimate of 358,000 maternal
      deaths annually. Infant mortality rate (IMR) is also high at 50 per 1000 (2009).
      Low budgetary spending on health, poverty, lower literacy, poor nutritional
      status, rural-urban divide and lack of trained workers in the health sector are
      cited as reasons for a high maternal mortality ratio and IMR. Increased spending
      by the Government of India on the health sector has started to show encouraging
      results. Recent assessments by world bodies like the World Health Organisation
      have given hope that MDGs 4 and 5 are achievable.

PMID- 21951503
TI  - Achieving Millennium Development Goals 4 and 5 in Nepal.
AB  - The under 5 child mortality rate in Nepal is on track to achieve the target of 54
      per 1000 live births by 2015 compared with 158 per 1000 live births in 1991. The
      maternal mortality rate also looks set to drop to its target of 134 per 100,000
      live births by 2015 from 539 per 100,000 live births in 1991. A 3-year interim
      plan (2008-11) was established to provide free basic health care for all citizens
      and the safe delivery incentive programme has proved to help progression towards
      achieving Millennium Development Goals 4 and 5. The development of a policy
      targeting women, children and vulnerable populations in hard to reach places is a
      key feature. The principle of a primary healthcare approach is applied in the
      development and implementation of strategy plans and programmes. The focus is on
      ensuring that there are functioning facilities for essential obstetric care at
      health facilities and provision of trained personnel at delivery.

PMID- 21951504
TI  - Achieving Millennium Development Goals 4 and 5 in Pakistan.
AB  - Pakistan is a signatory of many international development strategies including
      the Millennium Development Goals, and the government is committed to achieving a
      reduction in infant mortality rate from 72 to <55 per 1000 live births, the
      newborn mortality rate from 55 to <40 per 1000 live births and the maternal
      mortality rate from 276 per 100,000 to 140 per 100,000 live births by 2015.
      Maternal, newborn and child health play a key role in reducing poverty and
      promoting social and economic development. Improvement in maternal and child
      health is a priority agenda of the Government of Pakistan.

PMID- 21951505
TI  - Achieving Millennium Development Goals 4 and 5 in Sri Lanka.
AB  - Sri Lanka has an exemplary record in maternal and child health care. Provision of
      free education for over 60 years has helped to empower women. Medical care is
      accessible and provided free of charge. The maternal mortality ratio and the
      other indices of maternal and neonatal health have shown uninterrupted
      improvement since 1930. Midwives and the policy to increase their presence has
      been the key to success. Public health midwives provide care at the doorstep.
      Institutional midwives carry out the vast majority of deliveries, of which 99%
      occur in hospitals. Although on target with the Millennium Development Goals,
      some challenges that still remain are maternal death from postpartum haemorrhage
      and unsafe abortion, and perinatal deaths due to congenital abnormalities and
      prematurity.

PMID- 21951506
TI  - From home to hospital, a continuum of care: making progress towards Millennium
      Development Goals 4 and 5 in rural Bangladesh.
AB  - The Lutheran Aid to Medicine in Bangladesh (LAMB) health and development project
      in rural Bangladesh has developed an integrated maternal and child healthcare
      system providing appropriate, accessible and affordable health services for the
      poor, through a home-to-hospital, continuum-of-care approach. LAMB is thus an
      example of how high-quality maternity health services accessible to women of all
      socio-economic classes in a rural context can be provided, making progress
      towards Millennium Development Goals 4 and 5.

PMID- 21951507
TI  - Working with UK-based non-governmental organisations for better reproductive
      health in Nepal.
AB  - Over the years, strong health links have developed between Nepal and the UK with
      the overall aim of helping to achieve Millennium Development Goals 4 and 5. The
      nature of such health links is varied and ranges from education and training
      projects to service work, with a focus on direct medical care. The role of non
      governmental organisations (NGOs) in Nepal cannot be underestimated: there are
      over 5000 NGOs, working in all aspects of Nepali life. Most are not specifically
      dedicated to maternal, neonatal and reproductive health care, but have developed
      this area of interest in response to the identified needs in the local
      communities. The benefits from such health links are immense but, in times of
      limited funding of projects, it is increasingly important that different agencies
      work together to maximise the impact of projects.

PMID- 21951508
TI  - Dying to give birth: the Pakistan Liaison Committee's strategies to improve
      maternal health in Pakistan.
AB  - Pakistan has one of the worst maternal mortality ratios worldwide: 260-490 women
      die for every 100,000 live births in Pakistan. The Pakistan Liaison Group (PLG)
      was formed to work with and through the international office of the Royal College
      of Obstetricians and Gynaecologists (RCOG). It works with the RCOG representative
      committee in Pakistan to improve the health of women. It aims to contribute to
      improving maternal morbidity and mortality through strategies directed at
      improving the education and training of health professionals. In addition, the
      PLG aims to promote changes in the legislature to allow for the notification of
      maternal deaths so that accurate figures can be obtained, and so that health
      parameters can be accurately assessed and, in the long term, a confidential
      enquiry into maternal deaths can be initiated.

PMID- 21951509
TI  - The 'Making it Happen' programme in India and Bangladesh.
AB  - A training package designed to train health care providers in the management of
      common obstetric and newborn complications using a competency based 'skills and
      drills' approach is used in Bangladesh and India as one of the interventions
      under the 'Making it Happen' programme. The programme was commenced in 2009 and
      aims to reduce maternal and newborn mortality and morbidity by improving health
      care providers' capacity to deliver Essential (Emergency) Obstetric and Newborn
      Care (EOC&NC) thus increasing the availability and quality of these services.
      Preliminary results indicate that the training package has improved knowledge and
      skills of trained health care providers and ensures more signal functions of EOC
      are provided.

PMID- 21951510
TI  - Achieving Millennium Development Goals 4 and 5: a snapshot of life in rural
      India.
AB  - The case studies presented here illustrate the poignant reality of life for
      mothers and children in rural India. We highlight the challenges of achieving
      millennium development goals (MDGs) 4 and 5, by exploring the reasons behind
      maternal and childhood mortality using the three-delays model as a framework.
      Gender disparities, lack of empowerment of women, poor understanding of life
      threatening illness, the inability to know when and where to seek help, security
      issues, deficiencies in understanding cultural perceptions, poorly equipped
      health facilities and a lack of skilled personnel are all highlighted.

PMID- 21951511
TI  - Einar Rud and the syndrome that bears his name.

PMID- 21951512
TI  - Anticarcinogenic impact of interferon therapy on the progression of
      hepatocellular carcinoma in patients with chronic viral infection.
AB  - Hepatocellular carcinoma (HCC) is mainly caused by a persistent infection due to
      the hepatitis B or hepatitis C virus. The number of HCC cases is increasing in
      Asian and African countries, as well as in European and American countries.
      Interferon (IFN) therapy, used for type B chronic liver diseases, inhibits
      hepatic carcinogenesis in patients with compensated cirrhosis. However, there is
      insufficient evidence that IFN therapy inhibits hepatic carcinogenesis in
      patients with chronic hepatitis B. There are few cases of HCC due to chronic
      hepatitis B, and long-term follow-up periods verifying the inhibitory effect of
      IFN on hepatic carcinogenesis have not been obtained. To improve the prognosis of
      type B chronic liver diseases, it is important that hepatitis treatment follows
      guidelines in which a patient's age and the extent of hepatic fibrosis are taken
      into account. As for chronic hepatitis C, since a sustained virological response
      (SVR) in IFN therapy inhibits hepatic carcinogenesis and improves prognosis,
      treatment that aims for an SVR while taking into consideration host-sided and
      virus-sided factors is recommended for patients with type C chronic liver
      diseases. In areas with low incidence of HCC (e.g. USA), a large number of cases
      and a long-term follow-up period are needed before it can be accepted that IFN
      therapy inhibits hepatic carcinogenesis. After locally curative treatment of HCC,
      IFN therapy suppresses recurrence and improves survival rates.

PMID- 21951513
TI  - Predictors of recurrence of prolapse after procedure for prolapse and
      haemorrhoids.
AB  - AIM: The procedure for prolapse and haemorrhoids (PPH) is an effective surgical
      therapy for symptomatic haemorrhoids. Compared with haemorrhoidectomy, meta
      analysis has shown PPH to be less painful, with higher patient satisfaction and a
      quicker return to work, but at the cost of higher prolapse recurrence rates. This
      is the first report describing predictors of prolapse recurrence after PPH.
      METHOD: A cohort of patients with symptomatic haemorrhoids, treated with PPH in
      our hospital between 2002 and 2009, was retrospectively analysed. Multivariate
      analysis was performed to identify patient-related and perioperative predictors
      associated with persisting prolapse and prolapse recurrence. RESULTS: In total,
      159 consecutively enrolled patients were analysed. Persistence and recurrence of
      prolapse was observed in 16% of the patients. Increased surgical experience
      showed a trend towards lower recurrence rates. Multivariate analysis identified
      female gender, long duration of PPH surgery and the absence of muscle tissue in
      the resected specimen as independent predictors of postoperative persistence of
      prolapse of haemorrhoids. The absence of prior treatment with rubber band
      ligation (RBL) as well as increased PPH experience at the hospital showed a trend
      towards a higher rate of prolapse recurrence. CONCLUSION: In order to reduce
      recurrence of prolapse, PPH should be performed by a surgeon with adequate PPH
      experience, patients should be treated with RBL prior to PPH and a resection of
      mucosa with underlying muscle fibres should be strived for.

PMID- 21951514
TI  - A multilevel analysis on the relationship between neighbourhood poverty and
      public hospital utilization: is the high Indigenous morbidity avoidable?
AB  - BACKGROUND: The estimated life expectancy at birth for Indigenous Australians is
      10-11 years less than the general Australian population. The mean family income
      for Indigenous people is also significantly lower than for non-Indigenous people.
      In this paper we examine poverty or socioeconomic disadvantage as an explanation
      for the Indigenous health gap in hospital morbidity in Australia. METHODS: We
      utilised a cross-sectional and ecological design using the Northern Territory
      public hospitalisation data from 1 July 2004 to 30 June 2008 and socio-economic
      indexes for areas (SEIFA) from the 2006 census. Multilevel logistic regression
      models were used to estimate odds ratios and confidence intervals. Both total and
      potentially avoidable hospitalisations were investigated. RESULTS: This study
      indicated that lifting SEIFA scores for family income and education/occupation by
      two quintile categories for low socio-economic Indigenous groups was sufficient
      to overcome the excess hospital utilisation among the Indigenous population
      compared with the non-Indigenous population. The results support a reframing of
      the Indigenous health gap as being a consequence of poverty and not
      simplistically of ethnicity. CONCLUSIONS: Socio-economic disadvantage is a likely
      explanation for a substantial proportion of the hospital morbidity gap between
      Indigenous and non-Indigenous populations. Efforts to improve Indigenous health
      outcomes should recognise poverty as an underlying determinant of the health gap.

PMID- 21951515
TI  - Malaria parasites: elimination is not eradication.

PMID- 21951516
TI  - Predicting erectile dysfunction following surgical correction of Peyronie's
      disease without inflatable penile prosthesis placement: vascular assessment and
      preoperative risk factors.
AB  - INTRODUCTION: Surgical therapy remains the gold standard treatment for Peyronie's
      Disease (PD). Surgical options include plication, grafting, and placement of
      inflatable penile prosthesis (IPP). Postoperative erectile dysfunction (ED) is a
      potential complication for PD surgery without IPP. We present our large series
      follow-up to evaluate preoperative risk factors for postoperative ED. AIMS: The
      aim of this study is to evaluate preoperative risk factors for the development of
      ED following surgical correction of PD taking into account the degree of
      curvature, graft size, surgical approach, hypertension, hyperlipidemia, diabetes,
      smoking history, preoperative use of phosphodiesterase 5 inhibitors (PDE5), and
      preoperative duplex ultrasound findings including peak systolic and end diastolic
      velocities and resistive index. METHODS: We identified 218 men undergoing either
      tunica albuginea plication (TAP) or partial plaque excision with pericardial
      grafting for PD following a previously published algorithm between November 1992
      and April 2007. Preoperative and postoperative erectile function, curvature
      characteristics, presence of vascular risk factors, and duplex ultrasound
      findings were available on 109 patients. MAIN OUTCOME MEASURES: Our primary
      outcome measure is the development of ED after surgery for PD. RESULTS: Ten
      percent of TAP and 21% of plaque excision with grafting patients developed
      postoperative ED. Neither curve direction (P = 0.76), graft area (P = 0.78),
      surgical approach (P = 0.12), chronic hypertension (P = 0.51), hyperlipidemia (P
      = 0.87), diabetes (P = 0.69), nor smoking history (P = 0.99) were significant
      predictors of postoperative ED. No combination of risk factors was found to be
      predictive of postoperative ED. Preoperative use of PDE5 was not a significant
      predictor of postoperative ED (P = 0.33). Neither peak systolic, end diastolic,
      nor resistive index were significant predictors of ED (P = 0.28, 0.28, and 0.25,
      respectively). CONCLUSION: This long-term follow-up of a large published series
      suggests that neither preoperative risk factors nor preoperative duplex
      ultrasound findings are predictive of postoperative ED, thus reinforcing the use
      of previously published preoperative treatment algorithms.

PMID- 21951518
TI  - Estimating the budget impact of orphan medicines in Europe: 2010 - 2020.
AB  - BACKGROUND: Orphan drugs are a growing issue of importance to European healthcare
      policy makers. The success of orphan drug legislation in Europe has resulted in
      an increasing number of licensed medicines for rare diseases, and many more yet
      unlicensed products have received orphan drug designation. Increasingly the
      concerns amongst policy makers relate to issues of patient access and
      affordability, yet few studies have sought to estimate the future budget impact
      of orphan drugs. The aim of this study was to predict the total cost of orphan
      medicines in Europe between 2010 and 2020 as a percentage of total European
      pharmaceutical expenditure. METHODS: A disease-based epidemiological model was
      created based upon trends in the designation and approval of new orphan
      medicines, prevalence estimates for orphan diseases, and historical price and
      sales data for orphan drugs in Europe (defined as Eurozone + UK). The analysis
      incorporated two stages: 1) Predicting the number of diseases for which new
      orphan drugs will be approved over the next decade, based on an analysis of
      trends from the EU registry of orphan medicines; 2) Estimating the average ex
      factory drug cost across an orphan disease life cycle, from the year in which the
      first orphan medicine is launched to the point where the first medicine loses
      marketing exclusivity. The two sets of information were combined to quantify the
      annual cost of orphan drugs from 2010 through 2020. RESULTS: The results from the
      model predicted a steady increase in the cumulative number of diseases for which
      an orphan drug is approved, averaging just over 5 new diseases per year over the
      next 10 years. The annual per patient cost of existing orphan drugs was seen to
      vary between ?1,251 and ?407,631, with the median cost being ?32,242 per year.
      The share of the total pharmaceutical market represented by orphan drugs is
      predicted to increase from 3.3% in 2010 to a peak of 4.6% in 2016 after which it
      is expected to level off through 2020, as growth falls into line with that in the
      wider pharmaceutical market. In sensitivity analysis peak-year orphan drug budget
      impact ranged between 3% - 6.6%. CONCLUSIONS: Although European orphan drug
      legislation has led to an increase in the number of approved orphan drugs, the
      growth in cost, as a proportion of total pharmaceutical expenditure, is likely to
      plateau over the next decade as orphan growth rates converge on those in the
      broader pharmaceutical market. Given the assumptions and simplifications inherent
      in such a projection, there is uncertainty around the base case forecast and
      further research is needed to monitor how trends develop. However, fears that
      growth in orphan drug expenditure will lead to unsustainable cost escalation do
      not appear to be justified. Furthermore, based on the results of this budget
      impact forecast, the European orphan drug legislation is not leading to a
      disproportionate impact on pharmaceutical expenditure.

PMID- 21951519
TI  - The visual strategy specific to humans among hominids: a study using the gap
      overlap paradigm.
AB  - Although an extensive body of literature exists on the cognitive underpinnings of
      gaze movements in macaques and humans, few studies have investigated this topic
      from a broader evolutionary perspective. This study used the gap-overlap paradigm
      to examine the timing of the gaze movements by four hominid species: humans,
      chimpanzees, gorillas, and orangutans. The saccade latency involved in shifting
      the gaze from central to peripheral stimuli was measured and compared under two
      conditions, gap and overlap. The central stimulus disappeared shortly before the
      onset of the peripheral stimulus under the gap condition, but it remained under
      the overlap condition. Although all species demonstrated similar saccade
      latencies under the gap condition, the species clearly differed from one another
      under the overlap condition, which may suggest their similar perceptual and motor
      mechanism of making a saccade on the one hand and their differential strategies
      for coping with the competition between two activities involving fixation and
      initiation of a saccade (i.e. central vs. peripheral visual stimuli) on the other
      hand. In particular, humans showed longer saccade latency under the overlap
      condition compared to the other great apes, which may reflect this species'
      unique means of visual processing.

PMID- 21951517
TI  - Maternal HLA panel-reactive antibodies in early gestation positively correlate
      with chronic chorioamnionitis: evidence in support of the chronic nature of
      maternal anti-fetal rejection.
AB  - PROBLEM: Maternal tolerance of the fetus is essential for viviparity, yet anti
      fetal rejection occurs in several pregnancy complications. Chronic
      chorioamnionitis is a feature of anti-fetal cellular rejection. There is a robust
      association between chronic chorioamnionitis and maternal seropositivity for anti
      human leukocyte antigen (HLA) panel-reactive antibodies (PRA) at the time of
      delivery. This longitudinal study was performed to assess maternal HLA PRA status
      in early gestation and the temporal evolution of maternal HLA PRA in the context
      of chronic chorioamnionitis and, thereby, to determine whether HLA PRA during the
      course of pregnancy is useful for the detection of anti-fetal rejection. METHOD
      OF STUDY: Maternal sera obtained before 16 weeks of gestation and at delivery
      were analyzed for HLA PRA in cases with (N = 100) and without (N = 150) chronic
      chorioamnionitis. RESULTS: IgG (but not IgM) HLA class I and II PRA positivity at
      delivery was higher in cases with chronic chorioamnionitis than in those without
      chronic chorioamnionitis. IgG HLA class I PRA positivity before 16 weeks of
      gestation was higher in cases with chronic chorioamnionitis than in those without
      (30.3 versus 13.3%; P = 0.001). Positive conversion (negative HLA PRA before 16
      weeks of gestation but positive at delivery) of IgG HLA class I and II PRA was
      significantly associated with chronic chorioamnionitis. Fetal HLA class I antigen
      specific antibodies were confirmed in 12 of 16 mothers tested who were sensitized
      to HLA class I antigens before 16 weeks of gestation. CONCLUSION: Positive
      maternal HLA PRA before 16 weeks of gestation and the temporal evolution of
      maternal HLA PRA are associated with the presence of chronic chorioamnionitis at
      the time of delivery. Maternal IgG HLA PRA has the potential to be a monitoring
      tool of anti-fetal rejection. Furthermore, the findings herein indicate that
      subsets of fetuses are exposed to alloimmune HLA antibodies for months,
      especially in cases with chronic chorioamnionitis.

PMID- 21951520
TI  - Measuring enjoyment of physical activity in older adults: invariance of the
      physical activity enjoyment scale (paces) across groups and time.
AB  - The purpose of this study was to validate the Physical Activity Enjoyment Scale
      (PACES) in a sample of older adults. Participants within two different exercise
      groups were assessed at two time points, 6 months apart. Group and longitudinal
      invariance was established for a novel, 8-item version of the PACES. The
      shortened, psychometrically sound measure provides researchers and practitioners
      an expedited and reliable instrument for assessing the enjoyment of physical
      activity.

PMID- 21951521
TI  - Use of a handheld, computerized device as a decision support tool for stroke
      classification.
AB  - BACKGROUND: The Trial of ORG 10172 in Acute Stroke Treatment (TOAST)
      classification has been widely used to determine etiology of ischemic stroke.
      However, interrater reliability is known to be modest. The complexity of
      abstraction and the interpretation of various clinical and laboratory data might
      limit the accuracy of the TOAST classification. In this study, we developed a
      computerized clinical decision support system for stroke classification that can
      be used in a handheld device and tested whether this system can improve
      diagnostic accuracy and reliability. METHODS: Based on the TOAST classification,
      a logical algorithm was developed and implemented on a handheld device, named
      iTOAST. After answering six questions using the touch interface, the stroke
      subtype result is displayed on the screen. Four neurology residents were randomly
      assigned to classify stroke subtypes using iTOAST or the conventional method
      (cTOAST). Using a crossover design, they classified the stroke subtypes of 70
      patients. The standard subtypes were determined by three stroke experts.
      Correlated kappa coefficients using iTOAST compared with cTOAST were determined.
      RESULTS: The kappa (SE) value of iTOAST [0.790 (0.041), 95% CI: 0.707-0.870] was
      higher than that of cTOAST [0.692 (0.046), 95% CI: 0.600-0.782] (P<0.001).
      Neither sequence (P=0.857) nor period effect (P=0.999) was observed. CONCLUSIONS:
      The stroke classification tool using a handheld, computerized device was easy,
      accurate, and reliable over the conventional method. It may have additional
      benefit because a handheld, computerized device is accessible anytime and
      anywhere.

PMID- 21951523
TI  - Genetic differentiation among populations of a Hispaniolan trunk anole that
      exhibit geographical variation in dewlap colour.
AB  - Long neglected by classic island biogeographical theory, speciation within and
      among islands is increasingly recognized as a major contributor to insular
      diversity. Although the factors responsible for island speciation remain poorly
      understood, this process appears critically dependent on geographical variation
      and speciation in allopatry or parapatry. Here, we investigate geographical
      variation and speciation in a complex of Hispaniolan trunk anoles (Anolis
      distichus), where populations with strikingly distinct dewlap colours and
      patterns correspond with deeply divergent mtDNA structure. Using a multilocus,
      population-level analysis, we investigate whether these phenotypically and
      mitochondrially distinct populations exhibit the type of nuclear differentiation
      expected among species or incipient species. Along a transect that extends across
      a recently recessed marine barrier, our results are consistent with the
      persistence of an abrupt phenotypic and mitochondrial transition following
      secondary contact, in spite of little or no evidence for a reduction in nuclear
      gene flow. Along a second transect extending across a steep environmental
      gradient, our phenotypic and microsatellite data suggest a sharp genetic break
      with little or no admixture, whereas mtDNA recovers a signature of extensive
      unidirectional introgression. Together, these results are consistent with
      previous studies of Lesser Antillean anoles, suggesting that allopatric
      divergence alone is insufficient for speciation, whereas reduced gene flow and
      partial reproductive isolation may accumulate in the presence of ecological
      gradients. 

PMID- 21951522
TI  - Genome of alkaliphilic Bacillus pseudofirmus OF4 reveals adaptations that support
      the ability to grow in an external pH range from 7.5 to 11.4.
AB  - Bacillus pseudofirmus OF4 is an extreme but facultative alkaliphile that grows
      non-fermentatively in a pH range from 7.5 to above 11.4 and can withstand large
      sudden increases in external pH. It is a model organism for studies of
      bioenergetics at high pH, at which energy demands are higher than at neutral pH
      because both cytoplasmic pH homeostasis and ATP synthesis require more energy.
      The alkaliphile also tolerates a cytoplasmic pH > 9.0 at external pH values at
      which the pH homeostasis capacity is exceeded, and manages other stresses that
      are exacerbated at alkaline pH, e.g. sodium, oxidative and cell wall stresses.
      The genome of B. pseudofirmus OF4 includes two plasmids that are lost from some
      mutants without viability loss. The plasmids may provide a reservoir of mobile
      elements that promote adaptive chromosomal rearrangements under particular
      environmental conditions. The genome also reveals a more acidic pI profile for
      proteins exposed on the outer surface than found in neutralophiles. A large array
      of transporters and regulatory genes are predicted to protect the alkaliphile
      from its overlapping stresses. In addition, unanticipated metabolic versatility
      was observed, which could ensure requisite energy for alkaliphily under diverse
      conditions.

PMID- 21951525
TI  - Dissecting mechanisms of myelinated axon formation using zebrafish.
AB  - The myelin sheath is an essential component of the vertebrate nervous system, and
      its disruption causes numerous diseases, including multiple sclerosis (MS), and
      neurodegeneration. Although we understand a great deal about the early
      development of the glial cells that make myelin (Schwann cells in the peripheral
      nervous system and oligodendrocytes in the central nervous system), we know much
      less about the cellular and molecular mechanisms that regulate the later stages
      of differentiation that orchestrate myelin formation. Over the past decade, the
      zebrafish has been employed as a model with which to dissect the development of
      myelinated axons. Forward genetic screens have revealed new genes essential for
      myelination, as well as new roles for genes previously implicated in myelinated
      axon formation in other systems. High-resolution in vivo imaging in zebrafish has
      also begun to illuminate novel cell behaviors during myelinating glial cell
      development. Here we review the contribution of zebrafish research to our
      understanding of myelinated axon formation to date. We also describe and discuss
      many of the methodologies used in these studies and preview future endeavors that
      will ensure that the zebrafish remains at the cutting edge of this important area
      of research.

PMID- 21951524
TI  - Zebrafish models of germ cell tumor.
AB  - Germ cell tumors are neoplasms arising from pluripotent germ cells. In humans,
      these tumors occur in infants, children and young adults. The tumors display a
      wide range of histologic differentiation states which exhibit different clinical
      behaviors. Information about the molecular basis of germ cell tumors, and
      representative animal models of these neoplasms, are lacking. Germline
      development in zebrafish and humans is broadly conserved, making the fish a
      useful model to probe the connections between germ cell development and
      tumorigenesis. Here, we provide an overview of germline development and a brief
      review of germ cell tumor biology in humans and zebrafish. We also outline some
      methods for studying the zebrafish germline.

PMID- 21951526
TI  - In vivo analysis of white adipose tissue in zebrafish.
AB  - White adipose tissue (WAT) is the major site of energy storage in bony
      vertebrates, and also serves central roles in the endocrine regulation of energy
      balance. The cellular and molecular mechanisms underlying WAT development and
      physiology are not well understood. This is due in part to difficulties
      associated with imaging adipose tissues in mammalian model systems, especially
      during early life stages. The zebrafish (Danio rerio) has recently emerged as a
      new model system for adipose tissue research, in which WAT can be imaged in a
      transparent living vertebrate at all life stages. Here we present detailed
      methods for labeling adipocytes in live zebrafish using fluorescent lipophilic
      dyes, and for in vivo microscopy of zebrafish WAT.

PMID- 21951528
TI  - Hematopoietic stem cell development: using the zebrafish to identify the
      signaling networks and physical forces regulating hematopoiesis.
AB  - Hematopoietic stem cells (HSC) form the basis of the hematopoietic hierarchy,
      giving rise to each of the blood lineages found throughout the lifetime of the
      organism. The genetic programs regulating HSC development are highly conserved
      between vertebrate species. The zebrafish has proven to be an excellent model for
      discovering and characterizing the signaling networks and physical forces
      regulating vertebrate hematopoietic development.

PMID- 21951529
TI  - Zebrafish as a model for hemorrhagic stroke.
AB  - Blood vessels perform the fundamental role of providing conduits for the
      circulation of oxygen and nutrients and the removal of waste products throughout
      the body. Disruption of tissue perfusion by ischemia or hemorrhage of blood
      vessels has a range of devastating consequences including stroke. Stroke is a
      complex trait that includes both genetic and environmental risk factors. The
      zebrafish is an attractive model for the study of hemorrhagic stroke due to the
      conservation of the molecular mechanisms of blood vascular development among
      vertebrates and the experimental advantages that can be applied to zebrafish
      embryos and larva. This chapter will focus on the maintenance of vascular
      integrity and some of the seminal experimentation carried out in the zebrafish.

PMID- 21951527
TI  - Study of host-microbe interactions in zebrafish.
AB  - All animals are ecosystems, home to diverse microbial populations. Animal
      associated microbes play important roles in the normal development and physiology
      of their hosts, but can also be agents of infectious disease. Traditionally, mice
      have been used to study pathogenic and beneficial associations between microbes
      and vertebrate animals. The zebrafish is emerging as a valuable new model system
      for host-microbe interaction studies, affording researchers with the opportunity
      to survey large populations of hosts and to visualize microbe-host associations
      at a cellular level in living animals. This chapter provides detailed protocols
      for the analysis of zebrafish-associated microbial communities, the derivation
      and husbandry of germ-free zebrafish, and the modeling of infectious disease in
      different stages of zebrafish development via different routes of inoculation.
      These protocols offer a starting point for researchers to address a multitude of
      questions about animals' coexistence with microorganisms.

PMID- 21951530
TI  - A zebrafish model for VHL and hypoxia signaling.
AB  - The von Hippel-Lindau (VHL) tumor suppressor gene encodes an adaptor protein that
      regulates an array of transcription-dependent and -independent cellular and
      physiological processes. Mutations in this gene cause VHL disease, congenital
      polycythemia, and several sporadic tumor types. The last 15 years of fundamental
      and clinical research have helped define the phenotypic spectrum of VHL
      associated diseases and have introduced new cellular functions for pVHL. Here, we
      review the current knowledge of VHL function, and the different animal models for
      VHL disease, with a particular focus on the zebrafish. Zebrafish vhl mutants
      develop key aspects of the human disease condition, including activation of the
      hypoxia-inducible factor (HIF) signaling pathway, polycythemia, excessive
      neovascularization, macular edema, and pronephric abnormalities. The zebrafish
      vhl model offers a platform for the identification of genetic pathways,
      modifiers, and interactors involved in the development of VHL-associated
      neoplasms. Vhl mutants represent a unique and clinically relevant in vivo model
      for studying genotype-phenotype correlations and the identification of prognostic
      biomarkers. The amenability of zebrafish for chemical genetic screens will not
      only be helpful to identify novel therapeutic agents but may also reveal novel
      processes that require regulation by VHL.

PMID- 21951531
TI  - Basement membrane diseases in zebrafish.
AB  - Basement membranes (BMs) are a complex, sheet-like network of specialized
      extracellular matrix that underlies epithelial cells and surrounds muscle cells.
      They provide adherence between neighboring tissues, permit some flexibility of
      these adherent structures, and can act as a store for growth factors and as a
      guide for cell migration. The BM is not just a static structure; its deposition
      and remodeling are important for many processes including embryonic development,
      immune response, and wound healing. To date, dysfunction in BM deposition or
      remodeling has been linked to many human congenital disorders and diseases,
      affecting many different tissues in the body, including malformations,
      dystrophies, and cancer. However, many questions remain to be answered on the
      role BM proteins, and their mutations, play in the pathogenesis of human disease.
      In recent years, the zebrafish (Danio rerio) has emerged as a powerful animal
      model for human development and disease. In the first part of this chapter, we
      provide an overview of described defects caused by BM dysfunction in zebrafish,
      including development and function of notochord, muscle, central nervous system,
      skin, cardiovascular system, and kidney. In the second part, we will describe
      details of methods used to visualize and assess the structure of the BM in
      zebrafish, and to functionally analyze its different components.

PMID- 21951532
TI  - Zebrafish provides a novel model for lymphatic vascular research.
AB  - The mammalian lymphatic vasculature has an important function in the maintenance
      of tissue fluid homeostasis, absorption of dietary lipids, and immune
      surveillance. The lymphatic vessels are also recruited by many tumors as primary
      routes for metastasis and mediate immune responses in inflammatory diseases,
      whereas dysfunction of the lymphatic drainage leads to lymphedema. The
      characterization of a lymphatic vasculature in zebrafish has made the advantages
      of this small model organism, the suitability for intravital time-lapse imaging
      of developmental processes and the amenability for chemical and forward genetic
      screens, available to lymphatic vascular research. Here we review our current
      understanding of embryonic lymphangiogenesis in zebrafish, its molecular and
      anatomical similarities to mammalian lymphatic vascular development, and the
      possibilities zebrafish offers to complement mouse models and cell culture assays
      in the lymphangiogenesis field.

PMID- 21951533
TI  - Not all bones are created equal - using zebrafish and other teleost species in
      osteogenesis research.
AB  - Developmental osteogenesis and pathologies of mineralized tissues are areas of
      intense investigations in the mammalian field, but different from other areas of
      organ formation and developmental biology, zebrafish have been somewhat slow in
      joining the area of bone research. In recent years, however, genetic screens have
      provided a number of exciting mutants, and transgenic lines have been developed
      that permit visualization of osteoblasts and osteoclasts in vivo. We here review
      some of the recent literature and provide examples where insights from studies in
      zebrafish have complemented the information available from mammalian models or
      clinical studies. Furthermore, we provide a comparative overview about different
      forms of bone within the teleost lineage, and between teleosts and mammals.

PMID- 21951534
TI  - Zebrafish assays of ciliopathies.
AB  - In light of the growing list of human disorders associated with their
      dysfunction, primary cilia have recently come to attention as being important
      regulators of developmental signaling pathways and downstream processes. These
      organelles, present on nearly every vertebrate cell type, are highly conserved
      structures allowing for study across a range of species. Zebrafish, in
      particular, have emerged as useful organisms in which to explore the consequences
      of ciliary dysfunction and to model human ciliopathies. Here, we present a range
      of useful techniques that allow for investigation of various aspects of ciliary
      function. The described assays capitalize on the hallmark gastrulation defects
      associated with ciliary defects as well as relative ease of visualization of
      cilia in whole-mount embryos. Further, we describe our recently developed assay
      for querying functionality of human gene variants in live developing embryos.
      Finally, a current catalog of known zebrafish ciliary mutant lines is included.
      The techniques presented here provide a basic toolkit for in vivo investigation
      of both the biological and genetic mechanisms underlying a growing class of human
      diseases.

PMID- 21951535
TI  - Infectious disease modeling and innate immune function in zebrafish embryos.
AB  - The major cell types of the innate immune system, macrophages and neutrophils,
      develop during the first two days of zebrafish embryogenesis. The interaction of
      these immune cells with pathogenic microbes can excellently be traced in the
      optically transparent zebrafish embryos. Various tools and methods have recently
      been developed for visualizing and isolating the zebrafish embryonic innate
      immune cells, for establishing infections by different micro-injection
      techniques, and for analyzing the host innate immune response following microbial
      recognition. Here we provide practical guidelines for the application of these
      methodologies and review the current state of the art in zebrafish infectious
      disease research.

PMID- 21951536
TI  - Zebrafish as a model for the study of human cancer.
AB  - Zebrafish provide an exciting animal model system for the study of human cancers.
      During the last few years many zebrafish models of cancer have been generated
      that recapitulate human hematologic malignancies and solid tumors. Concurrent
      technological advances have significantly improved the genetic tractability and
      unique advantage of in vivo imaging in zebrafish, providing a means to dissect
      the molecular pathways underlying tumor initiation, progression and metastasis.
      Comparisons of cancer-associated gene expression profiles have demonstrated a
      high degree of similarity in the gene signatures of specific types of tumor cells
      in fish and humans, indicating that the contributing genetic pathways leading to
      cancer are evolutionarily conserved. Furthermore, the high fecundity, optical
      clarity and small embryo size of zebrafish continue to make it particularly
      amenable to performing whole-organism small molecule screens to identify targets
      for therapeutic development. This chapter reviews a wide array of these zebrafish
      cancer models and illustrates the advantages of the zebrafish system for
      exploring the molecular mechanisms governing cancer-related cellular processes.

PMID- 21951537
TI  - Generating and analyzing fish models of melanoma.
AB  - Melanoma is the most deadly form of skin cancer and incidence continues to rise
      rapidly (Gray-Schopfer et al., 2007). Melanoma develops from melanocytes, the
      pigmented cells that color our skin, hair, and eyes. Fish also have melanocytes,
      among other pigment cell types, and the fish and human developmental programme
      are highly conserved (Kelsh, 2004). The first fish models of melanoma were
      established in Xiphophorus, and more recently, transgenic melanoma models in
      zebrafish and medaka have been developed (Meierjohann and Schartl, 2006; Patton
      et al., 2010; Schartl et al., 2010). In this Chapter, we describe the basic
      techniques to generate genetic, environmental, and transgenic models of melanoma,
      discuss diagnoses, and describe standard molecular analysis techniques.

PMID- 21951538
TI  - Screening pancreatic oncogenes in zebrafish using the Gal4/UAS system.
AB  - Pancreatic cancer is a genetic disease in which somatic mutations in the KRAS
      proto-oncogene are detected in a majority of tumors. KRAS mutations represent an
      early event during pancreatic tumorigenesis, crucial for cancer initiation and
      progression. Recent studies, including comprehensive sequencing of the pancreatic
      cancer exome, have implicated the involvement of a number of additional core
      signaling pathways during pancreatic tumorigenesis. Improving our understanding
      of genetic interactions between KRAS and these additional pathways represents a
      critical challenge, as these interactions may provide novel opportunities for
      diagnosis and treatment. However, studying these interactions requires the
      expression of multiple transgenes in relevant cell types, an effort that has
      proven very difficult to achieve using gene targeted mice and is also technically
      challenging in zebrafish. Based on the ability of the Gal4 transcriptional
      activator to drive the expression of multiple transgenes under regulation of UAS
      (upstream activator sequence) regulatory elements, the Gal4/UAS system represents
      an attractive strategy for the study of genetic interactions. In this chapter, we
      review our experience using the Gal4/UAS system to model KRAS-initiated
      pancreatic cancer in zebrafish, as well as our early efforts using this system to
      study the influence of other cooperating oncogenes. We also describe techniques
      used to identify and characterize pancreatic tumors in adult transgenic fish.

PMID- 21951540
TI  - Transplantation in zebrafish.
AB  - Tissue or cell transplantation has been an extremely valuable technique for
      studying developmental potential of certain cell population, dissecting cell
      environment interaction relationship, identifying stem cells, and many other
      applications. One key technical requirement for performing transplantation assay
      is the capability of distinguishing the transplanted donor cells from the
      endogenous host cells, and tracing the donor cells over time. Zebrafish has
      emerged as an excellent model organism for performing transplantation assay,
      thanks to the transparency of embryos during development and even certain adults.
      Using transgenic techniques and fast-evolving imaging technology, fluorescence
      labeled donor cells can be easily identified and studied in vivo. In this
      chapter, we will first discuss the rationale of different types of zebrafish
      transplantation in both embryos and adults, and then focus on detailed methods of
      three types of transplantation: blastula/gastrula transplantation for mosaic
      analysis, stem cell transplantation, and tumor transplantation.

PMID- 21951539
TI  - Zebrafish models of rhabdomyosarcoma.
AB  - Rhabdomyosarcoma (RMS), an aggressive malignant neoplasm that shows features of
      skeletal muscle, is the most common soft tissue tumor of childhood. In children,
      the major subtypes are embryonal and alveolar. Although localized disease
      responds to a multimodal treatment, the prognosis for patients with high-risk
      features and metastasis remains dismal. Several in vivo models of RMS have been
      developed in mouse, human xenografts, zebrafish, and Drosophila to better
      understand the underlying mechanisms governing malignancy. The findings so far
      have indicated the potential role of skeletal muscle precursor cells in malignant
      transformation. To better understand histogenesis and different aspects of
      tumorigenesis in RMS, we have previously developed a robust zebrafish model of
      kRAS-induced RMS, which shares morphologic and immunophenotypic features with the
      human counterpart. Cross-species mircroarray comparisons confirm that conserved
      genetic pathways drive RMS growth. The ease for ex vivo manipulation allows the
      development of different transgenic and co-injection strategies to induce tumor
      formation in zebrafish. In contrast to other vertebrate model systems, the tumor
      onset in zebrafish is short, allowing for efficient study of different tumor
      processes including tumor growth, self-renewal, and maintenance.

PMID- 21951541
TI  - Disease modeling by gene targeting using microRNAs.
AB  - Zebrafish have proved to be a popular species for the modeling of human disease.
      In this context, there is a need to move beyond chemical-based mutagenesis and
      develop tools that target genes that are orthologous to those that are implicated
      in human heritable diseases. Targeting can take the form of creating mutations
      that are nonsense or mis-sense, or to mimic haploinsufficiency through the
      regulated expression of RNA effector molecules. In terms of the latter, we
      describe here the development and investigation of microRNA (miRNA)-based
      directed gene silencing methods in zebrafish. Unlike small interfering RNAs
      (siRNAs), miRNA-based methods offer temporal and spatial regulation of gene
      silencing. Proof-of-concept experiments demonstrate the efficacy of the method in
      zebrafish embryos, which provide the foundation for developing disease models
      using miRNA-based gene-targeting.

PMID- 21951542
TI  - Fluorescent imaging of cancer in zebrafish.
AB  - Zebrafish are an ideal model organism to research cancer. Zebrafish embryos and
      larvae are optically translucent, which has made imaging multiple processes in
      development and disease possible. When coupled with fluorescent imaging
      techniques, zebrafish are fast becoming a model of choice for following tumor
      formation. This is highlighted by recent studies using fluorescent proteins to
      image xenograft transplantation, neovascularization, growth responses to drug
      treatments, and self-renewal. Fluorescent labeled tumors can be generated in
      zebrafish by multiple methods including chemical mutagenesis, oncogene expression
      by mosaic or stable transgenesis, or genetic mutations that are predisposing to
      cancer. In this chapter, we highlight the studies that have employed fluorescence
      to follow critical aspects of tumorigenesis, with particular focus on providing
      methods for labeling, isolating, transplanting, and imaging fluorescently labeled
      tumors in zebrafish.

PMID- 21951544
TI  - Chemical screening in zebrafish for novel biological and therapeutic discovery.
AB  - Zebrafish chemical screening allows for an in vivo assessment of small molecule
      modulation of biological processes. Compound toxicities, chemical alterations by
      metabolism, pharmacokinetic and pharmacodynamic properties, and modulation of
      cell niches can be studied with this method. Furthermore, zebrafish screening is
      straightforward and cost-effective. Zebrafish provide an invaluable platform for
      novel therapeutic discovery through chemical screening.

PMID- 21951543
TI  - The role of Fanconi anemia/BRCA genes in zebrafish sex determination.
AB  - Fanconi anemia (FA) is a human disease of bone marrow failure, leukemia, squamous
      cell carcinoma, and developmental anomalies, including hypogonadism and
      infertility. Bone marrow transplants improve hematopoietic phenotypes but do not
      prevent other cancers. FA arises from mutation in any of the 15 FANC genes that
      cooperate to repair double stranded DNA breaks by homologous recombination.
      Zebrafish has a single ortholog of each human FANC gene and unexpectedly,
      mutations in at least two of them (fancl and fancd1(brca2)) lead to female-to
      male sex reversal. Investigations show that, as in human, zebrafish fanc genes
      are required for genome stability and for suppressing apoptosis in tissue culture
      cells, in embryos treated with DNA damaging agents, and in meiotic germ cells.
      The sex reversal phenotype requires the action of Tp53 (p53), an activator of
      apoptosis. These results suggest that in normal sex determination, zebrafish
      oocytes passing through meiosis signal the gonadal soma to maintain expression of
      aromatase, an enzyme that converts androgen to estrogen, thereby feminizing the
      gonad and the individual. According to this model, normal male and female
      zebrafish differ in genetic factors that control the strength of the late meiotic
      oocyte-derived signal, probably by regulating the number of meiotic oocytes,
      which environmental factors can also alter. Transcripts from fancd1(brca2)
      localize at the animal pole of the zebrafish oocyte cytoplasm and are required
      for normal oocyte nuclear architecture, for normal embryonic development, and for
      preventing ovarian tumors. Embryonic DNA repair and sex reversal phenotypes
      provide assays for the screening of small molecule libraries for therapeutic
      substances for FA.

PMID- 21951545
TI  - Using the zebrafish photomotor response for psychotropic drug screening.
AB  - Because psychotropic drugs affect behavior, we can use changes in behavior to
      discover psychotropic drugs. The original prototypes of most neuroactive
      medicines were discovered in humans, rodents and other model organisms. Most of
      these discoveries were made by chance, but the process of behavior based drug
      discovery can be made more systematic and efficient. Fully automated platforms
      for analyzing the behavior of embryonic zebrafish capture digital video
      recordings of animals in each individual well of a 96-well plate before, during,
      and after a series of stimuli. To analyze systematically the thousands of
      behavioral recordings obtained from a large-scale chemical screen, we transform
      these behavioral recordings into numerical barcodes, providing a concise and
      interpretable summary of the observed phenotypes in each well. Systems-level
      analysis of these behavioral phenotypes generate testable hypotheses about the
      molecular mechanisms of poorly understood drugs and behaviors. By combining the
      in vivo relevance of behavior-based phenotyping with the scale and automation of
      modern drug screening technologies, systematic behavioral barcoding represents a
      means of discovering psychotropic drugs and provides a powerful, systematic
      approach for unraveling the complexities of vertebrate behavior.

PMID- 21951546
TI  - Designing zebrafish chemical screens.
AB  - The zebrafish is proving to be highly amenable to in vivo small molecule
      screening. With a growing number of screens successfully completed, a rich
      interface is being created between disciplines that have historically used
      zebrafish (e.g., embryology and genetics) and disciplines focused on small
      molecules (e.g., chemistry and pharmacology). Navigating this interface requires
      consideration of the unique demands of conducting high-throughput screening in
      vivo. In this chapter, we discuss design elements of successful zebrafish
      screens, established screening methods, and approaches for mechanism of action
      studies following discovery of novel small molecules. These methods are enabling
      the zebrafish to have an increasingly positive impact on biomedical research and
      drug development.

PMID- 21951547
TI  - Methotrexate in the management of idiopathic granulomatous mastitis: review of
      108 published cases and report of four cases.
AB  - This study aimed to discuss the role of agents, such as steroids and methotrexate
      (MTX), in the treatment of patients with idiopathic granulomatous mastitis (IGM).
      Using Pubmed and Google Scholar data bases, a retrospective study was carried out
      on IGM cases treated with steroids and/or MTX between 1972 and 2010. Four IGM
      cases treated with MTX at our clinic were also summarized in this study. A total
      of 541 IGM cases since 1972, including ours, were retrospectively analyzed.
      Steroid treatment 5-85 mg was administered over 5 days-22 months to 112 patients
      aged 21-48 years. Recurrence occurred in 22 patients, steroid-induced diabetes
      mellitus in 5 patients, no response to treatment was observed in 4 patients, in 2
      patients, the mass decreased in size, and static disease was observed in one. The
      steroid treatment was changed to MTX treatment in 4 patients who had recurrence,
      5 with steroid-induced DM and in 4 who were nonrespondents. Three patients were
      started on steroid together with MTX as a primary treatment. Of the patients
      treated with MTX, a satisfactory result was obtained in 14 cases and in 2,
      mastectomy was performed because of recurrence despite the treatment with MTX.
      IGM is a troublesome condition that presents management problems due to the side
      effects of steroids. Our study demonstrates that the use of MTX in IGM cases has
      been effective in preventing complications, in resolving the inflammatory
      process, and in limiting side effects of corticosteroids.

PMID- 21951548
TI  - Sex differences in lipid profiles in relation to the progression of glucose
      abnormalities.
AB  - BACKGROUND: In the present study, we investigated the role of changes in blood
      lipids in the abolition of the lower cardiovascular risk associated with the
      female gender in individuals with type 2 diabetes mellitus (T2DM). METHODS: An
      oral glucose tolerance test (OGTT) was performed in 1091 consecutive patients
      (478 men and 613 women) and patients were divided into groups as follows: (i)
      those with normal glucose tolerance (NGT; n = 589); (ii) those with pre-diabetes
      (pre-T2DM), who were further divided into those with impaired fasting glucose
      (IFG; n = 212), impaired glucose tolerance (IGT; n = 84), and both IFG and IGT
      (IFG/IGT; n = 102); and (iii) those with T2DM (n = 104). Total cholesterol,
      triglycerides, high-density lipoprotein-cholesterol (HDL-C), low-density
      lipoprotein-cholesterol (LDL-C), apolipoprotein (apo) A-I, apoB, and the
      apoB:apoA-I ratio were determined in each patient. Differences in lipids between
      the different groups were assessed using Student's t-test. RESULTS: Significantly
      higher triglyceride levels and an apoB:apoA-I ratio were found in NGT men (P <
      0.0001), along with lower HDL-C and apoA-I (P < 0.0001). Men in the pre-T2DM
      group maintained a higher apoB:apoA-I ratio (P < 0.05) and lower HDL-C (P <
      0.0001) compared with women. In the T2DM group, only HDL-C was lower in men
      compared with women (P < 0.05). CONCLUSIONS: The progression of glucose
      intolerance from NGT to pre-T2DM and T2DM exhibits striking sex differences
      regarding the lipid profile. The data demonstrate a worsening of plasma lipid
      composition in women who become diabetic. This could explain, at least in part,
      the loss of the more favorable cardiovascular risk normally associated with NGT
      women.

PMID- 21951549
TI  - Octreotide for the treatment of diarrhoea in patients with ileal pouch anal
      anastomosis: a placebo-controlled crossover study.
AB  - AIM: Diarrhoea with urgency is a debilitating long-term complication of ileal
      pouch anal anastomosis (IPAA) after a proctocolectomy. Somatostatin analogues are
      used to control diarrhoea and high-output ostomies. Hence, we designed a
      prospective, double-blind, crossover trial to explore the efficacy and
      tolerability of octreotide to reduce diarrhoea in adult patients with IPAA.
      METHOD: Patients were randomized to octreotide subcutaneously (SC), 500 MUg three
      times daily (t.i.d.), or matching placebo SC for 7 days. Responders (a reduction
      in stool frequency of three or more stools per 24-h period and with a reduction
      in stool frequency of at least 30% after 7 days of treatment compared with
      baseline; the primary end-point) remained in the same group and nonresponders
      could cross over to the alternative treatment for 7 days. Open-label octeotide
      LAR 30 mg was offered to all responders on day 14. Flexible pouchoscopy with
      biopsies was performed at baseline in all patients and was repeated on days 7 and
      14 in patients with pouchitis. RESULTS: Fifteen patients (11 men, median age 52
      years), all with ulcerative colitis, were randomized. Three patients were
      withdrawn for side effects during the blinded phase. Response was achieved by two
      of 12 and two of 11 patients treated with octreotide or placebo, respectively
      (including crossover, P = 0.9). The median stool frequency remained stable in
      both groups [Deltaoctreotide: 0 (IQR, -4 to 0), Deltaplacebo: -1 (IQR, -1 to 1),
      P = 0.45]. Octreotide had no effect on the modified pouch disease activity index
      (mPDAI), and pouchitis persisted in five of six subjects with pouchitis at onset.
      One subject received open-label octreotide LAR. CONCLUSION: Octreotide has no
      clear beneficial effect on the stool pattern or on pouchitis severity in patients
      with high stool frequency after IPAA.

PMID- 21951551
TI  - Clinical characteristics of bacteraemia caused by extended-spectrum beta
      lactamase-producing Enterobacteriaceae in the era of CTX-M-type and KPC-type beta
      lactamases.
AB  - Clin Microbiol Infect 2012; 18: 887-893 ABSTRACT: A multicentre, case-control
      study was conducted to assess risk factors and patient outcomes of bacteraemia
      caused by Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBLs)
      and Klebsiella pneumoniae carbapenemases (KPCs). One hundred and five and 20
      patients with bacteraemia caused by ESBL-producing and KPC-producing organisms
      were matched to controls who had bacteraemia caused by non-ESBL/KPC-producing
      organisms, respectively. Independent risk factors for ESBL production included
      admission from a nursing home (OR 4.64; 95% CI 2.64-8.16), chronic renal failure
      (OR 2.09; 95% CI 1.11-3.92), the presence of a gastrostomy tube (OR 3.36; 95% CI
      1.38-8.18), length of hospital stay before infection (OR 1.02; 95% CI 1.01-1.03),
      transplant receipt (OR 2.48; 95% CI 1.24-4.95), and receipt of antibiotics with
      Gram-negative activity in the preceding 30 days (OR 1.76; 95% CI 1.00-3.08).
      Twenty-eight-day crude mortality rates for patients infected with ESBL-producing
      or KPC-producing organisms and controls were 29.1% (34/117) and 19.5% (53/272),
      respectively (OR 1.70; 95% CI 1.04-2.80). On multivariate analysis, inadequate
      empirical therapy (OR 2.26; 95% CI 1.18-4.34), onset of bacteraemia while in the
      intensive-care unit (OR 2.74; 95% CI 1.47-5.11), Apache II score (OR 1.17; 95% CI
      1.12-1.23) and malignancy (OR 2.66; 95% CI 1.31-5.41) were independent risk
      factors for mortality. CTX-M was the most common ESBL type in Escherichia coli,
      whereas SHV predominated in Klebsiella spp. and Enterobacter spp.

PMID- 21951552
TI  - The ins and outs of HIV-1 Tat.
AB  - HIV-1 encodes for the small basic protein Tat (86-101 residues) that drastically
      enhances the efficiency of viral transcription. The mechanism enabling Tat
      nuclear import is not yet clear, but studies using reporter proteins fused to the
      Tat basic domain indicate that Tat could reach the nucleus by passive diffusion.
      Tat also uses an unusual transcellular transport pathway. The first step of this
      pathway involves high-affinity binding of Tat to phosphatidylinositol (4,5)
      bisphosphate (PI(4,5)P(2)), a phospholipid that is concentrated in the inner
      leaflet of the plasma membrane and enables Tat recruitment at this level. Tat
      then crosses the plasma membrane to reach the outside medium. Although
      unconventional, Tat secretion by infected cells is highly active, and export is
      the major destination for HIV-1 Tat. Secreted Tat can bind to a variety of cell
      types using several different receptors. Most of them will allow Tat endocytosis.
      Upon internalization, low endosomal pH triggers a conformational change in Tat
      that results in membrane insertion. Later steps of Tat translocation to the
      target-cell cytosol are assisted by Hsp90, a general cytosolic chaperone.
      Cytosolic Tat can trigger various cell responses. Indeed, accumulating evidence
      suggests that extracellular Tat acts as a viral toxin that affects the biological
      activity of different cell types and has a key role in acquired immune-deficiency
      syndrome development. This review focuses on some of the recently identified
      molecular details underlying the unusual transcellular transport pathway used by
      Tat, such as the role of the single Trp in Tat for its membrane insertion and
      translocation.

PMID- 21951550
TI  - The clinical features of the overlap between COPD and asthma.
AB  - BACKGROUND: The coexistence of COPD and asthma is widely recognized but has not
      been well described. This study characterizes clinical features, spirometry, and
      chest CT scans of smoking subjects with both COPD and asthma. METHODS: We
      performed a cross-sectional study comparing subjects with COPD and asthma to
      subjects with COPD alone in the COPDGene Study. RESULTS: 119 (13%) of 915
      subjects with COPD reported a history of physician-diagnosed asthma. These
      subjects were younger (61.3 vs 64.7 years old, p=0.0001) with lower lifetime
      smoking intensity (43.7 vs 55.1 pack years, p=0.0001). More African-Americans
      reported a history of asthma (33.6% vs 15.6%, p<0.0001). Subjects with COPD and
      asthma demonstrated worse disease-related quality of life, were more likely to
      have had a severe COPD exacerbation in the past year, and were more likely to
      experience frequent exacerbations (OR 3.55 [2.19, 5.75], p<0.0001). Subjects with
      COPD and asthma demonstrated greater gas-trapping on chest CT. There were no
      differences in spirometry or CT measurements of emphysema or airway wall
      thickness. CONCLUSION: Subjects with COPD and asthma represent a relevant
      clinical population, with worse health-related quality of life. They experience
      more frequent and severe respiratory exacerbations despite younger age and
      reduced lifetime smoking history. TRIAL REGISTRATION: ClinicalTrials.gov:
      NCT00608764.

PMID- 21951553
TI  - Potential role of Thermus thermophilus and T. oshimai in high rates of nitrous
      oxide (N2O) production in ~80  degrees C hot springs in the US Great Basin.
AB  - Ambient nitrous oxide (N(2)O) emissions from Great Boiling Spring (GBS) in the US
      Great Basin depended on temperature, with the highest flux, 67.8 +/- 2.6 MUmol
      N(2)O-N m(-2) day(-1) , occurring in the large source pool at 82  degrees C. This
      rate of N(2)O production contrasted with negligible production from nearby soils
      and was similar to rates from soils and sediments impacted with agricultural
      fertilizers. To investigate the source of N(2)O, a variety of approaches were
      used to enrich and isolate heterotrophic micro-organisms, and isolates were
      screened for nitrate reduction ability. Nitrate-respiring isolates were
      identified by 16S rRNA gene sequencing as Thermus thermophilus (31 isolates) and
      T. oshimai (three isolates). All isolates reduced nitrate to N(2)O but not to
      dinitrogen and were unable to grow with N(2)O as a terminal electron acceptor.
      Representative T. thermophilus and T. oshimai strains contained genes with 96-98%
      and 93% DNA identity, respectively, to the nitrate reductase catalytic subunit
      gene (narG) of T. thermophilus HB8. These data implicate T. thermophilus and T.
      oshimai in high flux of N(2)O in GBS and raise questions about the genetic basis
      of the incomplete denitrification pathway in these organisms and on the fate of
      biogenic N(2)O in geothermal environments.

PMID- 21951554
TI  - Identifying prognostic factors for drug rash with eosinophilia and systemic
      symptoms (DRESS).
AB  - Drug rash with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous
      drug reaction. Although the severity-of-illness score (SCORTEN) has been proposed
      for toxic epidermal necrolysis (TEN) for 10 years, a prognostic score for DRESS
      is still lacking. To identify prognostic factors of DRESS patients during
      hospitalization in one medical health system in Taiwan. We retrospectively
      reviewed all patients with DRESS diagnosed by dermatologists in Chang Gung
      Memorial Hospital (CMGH) Health System from 2001 to 2010. To study prognostic
      factors, we collected data at early disease and maximal disease stages. 91
      individuals, including 13 dead patients, were evaluated. Five independent
      prognostic factors of death were found: heart rate > 90/min, white blood cells
      >12,000/mm(3) and respiratory rate >20/min (at early disease stage), coagulopathy
      and gastrointestinal bleeding (at maximal disease stage). In addition, systemic
      inflammatory response syndrome (SIRS) occurred at a much higher percentage among
      non-survivors throughout hospitalization. We found tachycardia, leukocytosis,
      tachypnea, coagulopathy, gastrointestinal bleeding and SIRS were associated with
      a poor outcome in DRESS patients. DRESS patients with persistent SIRS during
      hospitalization were also associated with a higher mortality risk. Early
      recognition and prompt intervention in these factors may improve outcome.

PMID- 21951555
TI  - Immunomodulatory properties of mesenchymal stem cells: cytokines and factors.
AB  - Mesenchymal stem cells (MSCs) are defined as undifferentiated cells that are
      capable of self renewal and differentiation into several cell types such as
      chondrocyte, adipocyte, osteocyte, myocyte, hepatocyte, and neuron-like cells.
      MSC can be isolated from bone marrow, umbilical cord blood, adipose tissue,
      placenta, periosteum, trabecular bone, synovium, skeletal muscle, and deciduous
      teeth. Immunomodulatory of MSCs is one of the important issues nowadays, because
      this aspect can be clinically applied for graft-versus-host and autoimmune
      diseases. In this review, we tried to discuss in detail about cytokines and
      factors such as members of the transforming growth factor superfamily
      (transforming growth factor-beta), hepatic growth factors (HGF), prostaglandin E2
      (PGE2), IL-10, indolamine 2,3-dioxygenase (IDO), nitric oxide (NO), heme
      oxygenase-1 (HO-1), and human leukocyte antigen-G (HLA-G) that are involved in
      immunomodulatory of MSCs.

PMID- 21951556
TI  - Susceptibility to natural killer cell-mediated lysis of colon cancer cells is
      enhanced by treatment with epidermal growth factor receptor inhibitors through
      UL16-binding protein-1 induction.
AB  - We have previously shown that inhibition of intracellular signaling pathways by
      treatment with quercetin induced the expression of natural killer cell group 2D
      (NKG2D) ligands on cancer cells and made the cells sensitive to natural killer
      (NK)-cell mediated cytotoxicity. In the present study, we investigated whether
      epidermal growth factor receptor (EGFR) inhibitors could induce the expression of
      NKG2D ligands in colon cancer cells. Treatment with EGFR inhibitors predominantly
      increased the levels of mRNA transcripts and surface protein of UL16-binding
      protein-1 (ULBP1) in various colon cancer cells, including KM12, Caco-2, HCT-15,
      and HT-29, which express EGFR, and increased susceptibility of these colon cancer
      cells to NK-92 cells. The expression of ULBP1 was not induced by inhibitors of
      nuclear factor-kappaB, phosphatidylinositol 3 kinase, and MAPK, but was induced
      by inhibitors of PKC, and the induction of ULBP1 expression with EGFR inhibitors
      was prevented by treatment with PMA in colon cancer cells. A transcription
      factor, activator protein-2 alpha (AP-2alpha), which has a suppressive effect on
      ULBP1 transcription, was prevented from binding to the ULBP1 promoter by
      treatment with EGFR inhibitors. The present study suggests that EGFR inhibitors
      can enhance the susceptibility to NK cell-mediated lysis of colon cancer cells by
      induction of ULBP1 via inhibition of the PKC pathway.

PMID- 21951557
TI  - Penile fracture seems more likely during sex under stressful situations.
AB  - INTRODUCTION: The unusual event of penile fracture occurs when there is a
      disruption of the tunica albuginea surrounding engorged erectile tissue during
      aggressive sexual behavior. There is often an audible crack and rapid
      detumescence with subcutaneous hemorrhage that follows. AIMS: Medical literature
      has described the etiology and treatment of penile fracture. We report the
      remarkably unusual social situations of a series of patients who sustained this
      unique injury. METHODS: We conducted a retrospective chart review of 16 patients
      whose injury was severe enough to require surgical repair at the University of
      Maryland between 2007 and 2011. Particular attention was paid to the intake
      interview in the emergency department and the postoperative chart notes by the
      attending urologist to ascertain out-of-the-ordinary social situations in which
      the injury was sustained. MAIN OUTCOME MEASURES: The occurrence of penile
      fracture is sufficiently rare that the author was able to interact personally
      with most of the patients. The patients were remarkably forthcoming with the
      personal social dynamics of the sexual encounter. RESULTS: Half of these penile
      fracture patients sustained the injury during an extramarital affair. Only three
      patients sustained the injury in a bedroom; the remainder was in out-of-the
      ordinary locations for sexual intercourse, e.g., cars, elevator, the workplace,
      and public restrooms. CONCLUSIONS: Penile fracture patients appear to be a unique
      population of men who are having sexual intercourse under stressful situations.
      Extramarital affairs and out-of-the-ordinary locations appear common in patients
      sustaining this relatively rare injury.

PMID- 21951558
TI  - Immobilization strategies to develop enzymatic biosensors.
AB  - Immobilization of enzymes on the transducer surface is a necessary and critical
      step in the design of biosensors. An overview of the different immobilization
      techniques reported in the literature is given, dealing with classical
      adsorption, covalent bonds, entrapment, cross-linking or affinity as well as
      combination of them and focusing on new original methods as well as the recent
      introduction of promising nanomaterials such as conducting polymer nanowires,
      carbon nanotubes or nanoparticles. As indicated in this review, various
      immobilization methods have been used to develop optical, electrochemical or
      gravimetric enzymatic biosensors. The choice of the immobilization method is
      shown to represent an important parameter that affects biosensor performances,
      mainly in terms of sensitivity, selectivity and stability, by influencing enzyme
      orientation, loading, mobility, stability, structure and biological activity.

PMID- 21951559
TI  - Ankles back in randomized controlled trial (ABrCt): braces versus neuromuscular
      exercises for the secondary prevention of ankle sprains. Design of a randomised
      controlled trial.
AB  - BACKGROUND: Ankle sprains are the most common sports and physical activity
      related injury. There is extensive evidence that there is a twofold increased
      risk for injury recurrence for at least one year post injury. In up to 50% of all
      cases recurrences result in disability and lead to chronic pain or instability,
      requiring prolonged medical care. Therefore ankle sprain recurrence prevention in
      athletes is essential. This RCT evaluates the effect of the combined use of
      braces and neuromuscular training (e.g. proprioceptive training/sensorimotor
      training/balance training) against the individual use of either braces or
      neuromuscular training alone on ankle sprain recurrences, when applied to
      individual athletes after usual care. METHODS/DESIGN: This study was designed as
      three way randomized controlled trial with one year follow-up. Healthy
      individuals between 12 and 70 years of age, who were actively participating in
      sports and who had sustained a lateral ankle sprain in the two months prior to
      inclusion, were eligible for inclusion. After subjects had finished ankle sprain
      treatment by means of usual care, they were randomised to any of the three study
      groups. Subjects in group 1 received an eight week neuromuscular training
      program, subjects in group 2 received a sports brace to be worn during all sports
      activities for the duration of one year, and group 3 received a combination of
      the neuromuscular training program and a sports brace to be worn during all
      sports activities for the duration of eight weeks. Outcomes were assessed at
      baseline and every month for 12 months therafter. The primary outcome measure was
      incidence of ankle sprain recurrences. Secondary outcome measures included the
      direct and indirect costs of recurrent injury, the severity of recurrent injury,
      and the residual complaints during and after the intervention. DISCUSSION: The
      ABrCt is the first randomized controlled trial to directly compare the secondary
      preventive effect of the combined use of braces and neuromuscular training,
      against the use of either braces or neuromuscular training as separate secondary
      preventive measures. This study expects to identify the most effective and cost
      efficient secondary preventive measure for ankle sprains. The study results could
      lead to changes in the clinical guidelines on the prevention of ankle sprains,
      and they will become available in 2012. TRIAL REGISTRATION: Netherlands Trial
      Register (NTR): NTR2157.

PMID- 21951561
TI  - Kinship of long-term associates in the highly social sperm whale.
AB  - The evolution of stable social groups can be promoted by both indirect and direct
      fitness benefits. Sperm whales (Physeter macrocephalus) are highly social, with a
      hierarchical social structure based around core groups of adult females and
      subadults, a rare level of complexity among mammals. We combined long-term
      satellite tracking (ranging from 11 to 607 days) of 51 individual sperm whales
      with genetic kinship analysis to assess the pattern of kin associations within
      and among coherent social units. Unlike findings for other species with similar
      social structure, we find no consistent correlation between kinship and
      association apart from close associations between two pairs of first-order
      relatives. A third pair of first-order relatives did not associate, and overall,
      the mean relatedness was the same within as among social groups. However, social
      behaviour can also be promoted by ecological factors such as resource dispersion.
      We assessed putative foraging behaviour during travel from the satellite-tracking
      data, which suggested that prey resources were dispersed and unpredictable, a
      condition that could promote living in groups.

PMID- 21951560
TI  - Noise characteristics of the Escherichia coli rotary motor.
AB  - BACKGROUND: The chemotaxis pathway in the bacterium Escherichia coli allows cells
      to detect changes in external ligand concentration (e.g. nutrients). The pathway
      regulates the flagellated rotary motors and hence the cells' swimming behaviour,
      steering them towards more favourable environments. While the molecular
      components are well characterised, the motor behaviour measured by tethered cell
      experiments has been difficult to interpret. RESULTS: We study the effects of
      sensing and signalling noise on the motor behaviour. Specifically, we consider
      fluctuations stemming from ligand concentration, receptor switching between their
      signalling states, adaptation, modification of proteins by phosphorylation, and
      motor switching between its two rotational states. We develop a model which
      includes all signalling steps in the pathway, and discuss a simplified version,
      which captures the essential features of the full model. We find that the noise
      characteristics of the motor contain signatures from all these processes, albeit
      with varying magnitudes. CONCLUSIONS: Our analysis allows us to address how cell
      to-cell variation affects motor behaviour and the question of optimal pathway
      design. A similar comprehensive analysis can be applied to other two-component
      signalling pathways.

PMID- 21951562
TI  - mRNA expression levels and genetic status of genes involved in the EGFR and NF
      kappaB pathways in metastatic non-small-cell lung cancer patients.
AB  - BACKGROUND: Metastatic non-small-cell lung cancer (NSCLC) has a dismal prognosis.
      EGFR is overexpressed or mutated in a large proportion of cases. Downstream
      components of the EGFR pathway and crosstalk with the NF-kappaB pathway have not
      been examined at the clinical level. We explored the prognostic significance of
      the mRNA expression of nine genes in the EGFR and NF-kappaB pathways and of BRCA1
      and RAP80 in patients in whom EGFR and K-ras gene status had previously been
      determined. In addition, NFKBIA and DUSP22 gene status was also determined.
      METHODS: mRNA expression of the eleven genes was determined by QPCR in 60
      metastatic NSCLC patients and in nine lung cancer cell lines. Exon 3 of NFKBIA
      and exon 6 of DUSP22 were analyzed by direct sequencing. Results were correlated
      with outcome to platinum-based chemotherapy in patients with wild-type EGFR and
      to erlotinib in those with EGFR mutations. RESULTS: BRCA1 mRNA expression was
      correlated with EZH2, AEG-1, Musashi-2, CYLD and TRAF6 expression. In patients
      with low levels of both BRCA1 and AEG-1, PFS was 13.02 months, compared to 5.4
      months in those with high levels of both genes and 7.7 months for those with
      other combinations (P=0.025). The multivariate analysis for PFS confirmed the
      prognostic role of high BRCA1/AEG-1 expression (HR, 3.1; P=0.01). Neither NFKBIA
      nor DUSP22 mutations were found in any of the tumour samples or cell lines.
      CONCLUSIONS: The present study provides a better understanding of the behaviour
      of metastatic NSCLC and identifies the combination of BRCA1 and AEG-1 expression
      as a potential prognostic model.

PMID- 21951563
TI  - Complete genome of Candidatus Chloracidobacterium thermophilum, a chlorophyll
      based photoheterotroph belonging to the phylum Acidobacteria.
AB  - Candidatus Chloracidobacterium thermophilum, which naturally inhabits microbial
      mats of alkaline siliceous hot springs in Yellowstone National Park, is the only
      known chlorophototroph in the phylum Acidobacteria. The Ca. C. thermophilum
      genome was composed of two chromosomes (2,683,362 bp and 1,012,010 bp), and both
      encoded essential genes. The genome included genes to produce chlorosomes, the
      Fenna-Matthews-Olson protein, bacteriochlorophylls a and c as principal pigments,
      and type-1, homodimeric reaction centres. Ca. C. thermophilum is an aerobic
      photoheterotroph that lacks the ability to synthesize several essential
      nutrients. Key genes of all known carbon fixation pathways were absent, as were
      genes for assimilatory nitrate and sulfate reduction and vitamin B(12) synthesis.
      Genes for the synthesis of branched-chain amino acids (valine, isoleucine and
      leucine) were also absent, but genes for catabolism of these compounds were
      present. This observation suggested that Ca. C. thermophilum may synthesize
      branched-chain amino acids from an intermediate(s) of the catabolic pathway by
      reversing these reactions. The genome encoded an aerobic respiratory electron
      transport chain that included NADH dehydrogenase, alternative complex III and
      cytochrome oxidase. The chromosomes of the laboratory isolate were compared with
      assembled, metagenomic scaffolds from the major Ca. C. thermophilum population in
      hot-spring mats. The larger chromosomes of the two populations were highly
      syntenous but significantly divergent (~13%) in sequence. In contrast, the
      smaller chromosomes have undergone numerous rearrangements, contained many
      transposases, and might be less constrained by purifying selection than the large
      chromosomes. Some transposases were homologous to those of mat community members
      from other phyla.

PMID- 21951564
TI  - A review of combined orbital decompression and lower eyelid recession surgery for
      lower eyelid retraction in thyroid orbitopathy.
AB  - BACKGROUND/AIMS: Eyelid retraction in thyroid orbitopathy is traditionally
      managed with staged surgery after orbital decompression. We review the benefit of
      concurrent inferior retractor recession at the time of orbital decompression when
      closing a swinging-eyelid flap. METHODS: A retrospective, comparative, non
      randomised clinical audit of 34 eyes of 22 patients with thyroid orbitopathy over
      a 3-year period was carried out. Patients were divided into a combined orbital
      decompression and inferior retractor recession (with lateral horn release) group
      (RG, n=13) and an orbital decompression non-recession group (NRG, n=21). Groups
      were matched for age, walls decompressed, volume of intraconal fat excised and
      improvement in exophthalmometry. Surgery involved one to three wall
      decompressions and intraconal fat excision via a swinging eyelid and
      transcaruncular approach. We report outcomes at 6 months based on postoperative
      standard photographs. Lower eyelid height, inferior scleral show and lower eyelid
      lateral flare were recorded by two blinded, independent assessors. RESULTS: The
      RG achieved a greater improvement in lower eyelid elevation (1.8 +/- 0.8 mm)
      compared to the NRG (1.1 +/- 0.8 mm) (p=0.042). The RG (58%) and NRG (40%) had
      improvement of lower lid lateral flare. Mean scleral show improved in both the RG
      (1.3 mm) and NRG (0.9 mm). No lower eyelid complications occurred. CONCLUSION:
      Combining orbital decompression with concurrent inferior retractor recession at
      the time of swinging-eyelid flap closure is safe and improves lower lid height
      postoperatively compared to decompression alone.

PMID- 21951565
TI  - Prediction error and myopic shift after intraocular lens implantation (IOL) in
      paediatric cataract patients.

PMID- 21951566
TI  - Validity and reliability of the TED-QOL: a new three-item questionnaire to assess
      quality of life in thyroid eye disease.
AB  - AIM: To develop and test a user-friendly questionnaire for rapidly assessing
      quality of life (QOL) in thyroid eye disease (TED). METHODS: A three-item
      questionnaire, the TED-QOL, was designed and compared to the 16-item Graves
      Ophthalmopathy (GO)-QOL and the nine-item GO-Quality of Life Scale (QLS). 100
      patients with TED were administered all three questionnaires on two occasions.
      Results were compared to clinical severity scores (Vision, Inflammation,
      Strabismus, Appearance (VISA) classification). Main outcomes were construct and
      criterion validity, test-retest reliability, duration, comprehension and
      completion rates. TED-QOL correlated strongly with the other questionnaires for
      corresponding items (Pearson correlation: appearance 0.71, 0.62; functioning
      0.69, 0.66; overall QOL 0.53). Test-retest analysis demonstrated good reliability
      for all three questionnaires (intraclass correlations: TED-QOL 0.81, 0.74, 0.87;
      GO-QOL 0.81, 0.82; GO-QLS 0.74, 0.86, 0.67). TED-QOL was significantly faster to
      complete (1.6 min vs GO-QOL 3.1 min, GO-QLS 2.7 min, p<0.0001) and had a higher
      completion rate (100% vs GO-QOL 78%, GO-QLS 94%). There was only moderate
      correlation between items on all three questionnaires and VISA scores.
      CONCLUSION: The TED-QOL is rapid and easy to complete and analyse and has similar
      validity and reliability to longer questionnaires. All questionnaires showed only
      moderate correlation with disease severity, emphasising the discrepancy between
      objective and subjective assessments and the importance of measuring both.

PMID- 21951567
TI  - Outcomes following three-line vision loss during treatment of neovascular age
      related macular degeneration: subgroup analyses from MARINA and ANCHOR.
AB  - AIM: This study aims to assess the impact of continued ranibizumab treatment for
      neovascular age-related macular degeneration on patients from the MARINA and
      ANCHOR randomised clinical studies who lost >= 3 lines of best-corrected visual
      acuity (BCVA) at any time during the first year of treatment. METHODS: Baseline
      characteristics, mean BCVA over time and ocular adverse events (AEs) were
      evaluated both for patients whose BCVA loss occurred at any post-baseline visit
      and for patients whose BCVA loss was acute. The visit when the >= 3-line BCVA
      loss was detected was defined as the new baseline. RESULTS: Continued monthly
      ranibizumab treatment led to an improvement in mean BCVA from the new baseline.
      On average, patients with acute BCVA loss gained 11.9 letters at 3 months after
      the new baseline, compared with 0.3 letters gained with sham. No strong signals
      were detected in patient demographics and baseline characteristics for prognostic
      markers of BCVA loss. Furthermore, there was no pattern in the AE profile of
      patients with acute BCVA loss to suggest that BCVA recovery could be attributed
      to spontaneously resolving AEs. CONCLUSION: Continued ranibizumab treatment
      appears to be beneficial for patients with neovascular age-related macular
      degeneration who experience a >= 3-line BCVA loss during the first year of
      treatment.

PMID- 21951568
TI  - Is high-resolution spectral domain optical coherence tomography reliable in
      nystagmus?

PMID- 21951569
TI  - Treatment of non-arteritic anterior ischaemic optic neuropathy.

PMID- 21951570
TI  - The temporal and nasal retinal arteriolar and venular angles in preterm infants.
AB  - AIM: To determine the angle between the temporal or nasal retinal vessels in
      preterm infants and to determine the relationship of these angles to birthweight
      (BW), gestational age (GA) and retinopathy of prematurity (ROP) status. METHODS:
      Colour digital images were acquired during ROP screening examinations in infants
      born with a range of BWs and GAs between 33 and 42 weeks postmenstrual age. Four
      retinal vessel angles were measured: temporal venular angle, temporal arteriolar
      angle (tAA), nasal venular angle and nasal arteriolar angle. Measurements were
      performed by Computer-Aided Image Analysis of the Retina, a validated semi
      automated computer software program. The relationship of each of four angles to
      BW and also to GA was determined using Mann-Whitney test and Spearman's rho,
      respectively. RESULTS: tAA was significantly narrower in infants with ROP and
      correlated positively with BW and GA. The other vessel angles, temporal venular
      angle, nasal arteriolar angle and nasal venular angle, showed no significant
      correlation with BW, GA or ROP status. CONCLUSION: The retinal vessel angles can
      be quantified in a simple repeatable manner. tAA correlated positively with BW
      and GA, and was significantly narrower in infants with stage 3 ROP than in those
      without ROP or with mild disease.

PMID- 21951571
TI  - Reaction time as a measure of enhanced blue-light mediated cognitive function
      following cataract surgery.
AB  - BACKGROUND/AIMS: Since 2002 the discovery of a novel population of intrinsically
      photosensitive retinal ganglion cells, expressing the photopigment melanopsin,
      has attracted broad interest in human blue-light mediated non-visual effects
      including circadian regulation and cognitive function. Ageing is associated with
      insomnia and cognitive decline. It has been postulated that reduced blue-light
      transmission through the formation of cataract impairs melanopsin dependant non
      visual brain responses mediated by intrinsically photosensitive retinal ganglion
      cells. We aimed to establish if any objective improvement in cognition could be
      demonstrated using a reaction time task (RTT) following cataract surgery and
      intraocular lens implantation. METHODS: Following strict inclusion and exclusion
      criteria, 15 patients (age range 59-87, mean 75.4 years) with bilateral cataract
      performed the RTT before and after surgery on one eye. The mean and the SD of two
      modalities of reaction time, namely complex reaction time and simple reaction
      time, were measured and analysed. RESULTS: Responses became both quicker and more
      consistent following surgery, with statistically significant improvements in the
      complex reaction time (p=0.016) and the complex reaction time SD (p=0.055), which
      were not due to a learning effect or improved vision. CONCLUSION: The results
      suggest that improved blue-light transmission following cataract surgery has a
      beneficial effect on cognitive function. We advocate the RTT as an objective
      platform for exploring these benefits in large sample randomised controlled
      trials.

PMID- 21951572
TI  - Comprehensive diabetes cardiovascular treatment = sugar + blood pressure +
      lipids.

PMID- 21951573
TI  - Changes in the levels of factor VIII and von Willebrand factor in the puerperium.
AB  - To determine changes in Factor VIII (FVIII) and von Willebrand Factor (VWF) in
      the first 3 days of the puerperium. A prospective study assessing FVIII clotting
      activity, VWF activity and antigen levels in 95 women (with singleton
      uncomplicated pregnancies) during labour and on days 1, 2 and 3 of the
      puerperium. There were no significant differences in FVIII, VWF:Ag and VWF:CB on
      days 1 and 2 of the puerperium compared with levels during labour. There was a
      significant decrease in VWF:Ag (P = 0.009) and VWF:CB (P = 0.04) on day 3. Age,
      ethnicity, duration of labour and mode of delivery did not have any significant
      effect on the changes in FVIII and VWF levels. The pregnancy induced increase in
      FVIII and VWF is maintained in the first 48 h after delivery. VWF levels start to
      decline on day 3 postdelivery.

PMID- 21951575
TI  - The properties of bio-energy transport and influence of structure nonuniformity
      and temperature of systems on energy transport along polypeptide chains.
AB  - A new theory of bio-energy transport along protein molecules in living systems,
      where the energy is released by hydrolysis of adenosine triphosphate (ATP), is
      proposed based on some physical and biological reasons. In the new theory, the
      Davydov's Hamiltonian and wave function of the systems are simultaneously
      modified and extended. A new interaction has been added into Davydov's
      Hamiltonian. The wave function of the excitation state of single particles for
      the excitons in the Davydov model is replaced by a new wave function of two
      quanta quasicoherent state. In such a case, the bio-energy is transported by the
      new soliton, which differs from the Davydov's soliton. The soliton is formed
      through self- trapping of two excitons interacting amino acid residues. The
      exciton is generated by vibrations of amide-I (CO stretching) arising from the
      energy of hydrolysis of ATP. The properties of the new soliton are extensively
      studied by analytical method and its lifetime is calculated using the nonlinear
      quantum perturbation theory and a wide ranges of parameter values relevant to
      protein molecules. The lifetime of the new soliton at the biological temperature
      300 K is enough large and belongs to the order of 10-10 s, or tau/tau0>=700, in
      which the soliton can transports over several hundreds amino acid residues. These
      studied results show clearly that the new soliton is thermally stable and has so
      larger lifetime that it can play an important role in biological processes. Thus
      the new model is a candidate of the bio-energy transport mechanism in protein
      molecules. In the meanwhile, the influences of structure nonuniformity in protein
      molecules and temperature of the systems on the states and properties of the
      soliton transport of bio-energy are numerically simulated and studied by the
      fourth-order Runge-Kutta method. The structure nonuniformity arises from the
      disorder distributions of masses of amino acid residues, side groups and
      impurities, which results also in the fluctuations of the spring constant of
      protein molecules, dipole-dipole interaction between the neighboring amides,
      exciton-phonon (vibration of amino acids)interaction, chain-chain interaction
      among the three channels and ground state energy of the systems. We investigated
      the behaviors and states of the new solitons in a single protein molecular chain
      and alpha-Helix protein molecules with three channels under influences of the
      structure nonuniformity. We prove first that the bio-energy is transported by a
      soliton, which can move without dispersion, retaining its shape, velocity and
      energy in a uniform and periodic protein molecule. When the structure
      nonuniformity exists, although the fluctuations of the spring constant, dipole
      dipole interaction constant, exciton-phonon coupling constant and ground state
      energy and the nonuniformity distributions of masses of amino acid residues can
      change the states and properties of motion of new soliton, they are still quite
      stable and very robust against these structure nonuniformities, i.e., even there
      are a larger structure nonuniformity in the protein molecules, the new solitons
      cannot be still dispersed. If the effects of thermal perturbation of medium on
      the soliton in nonuniform proteins is considered again, the new soliton can
      transport also over a larger spacing of 400 amino acids and has a longer time
      period of 300 ps, it is still thermally stable up to 320 K under the influence of
      the above structure nonuniformities. However, the new soliton disperses in the
      case of a higher temperature of 325 K and in more large structure nonuniformity.
      Thus, we determine that the new soliton's lifetime and critical temperature are
      300 ps and 320 K, respectively. These results are also consistent with analytical
      data obtained via quantum perturbed theory. For alpha-Helix protein molecules
      with three channels, the results obtained show that the structure nonuniformity
      and quantum fluctuation can change the states and features of the new solitons,
      for example, the amplitudes, energies and velocities of the new soliton are
      decreased, but the solitons have been not destroyed, they can still transport
      steadily along the molecular chains retaining energy and momentum. When the
      quantum fluctuations are larger, such as, structure disorders and quantum
      fluctuations of 0.67<alpha(K)<2, DeltaW=+/-8%W-, DeltaJ=+/-1%J-,
      Delta(chi1+chi2)=+/-3%(chi-1+chi-2) and DeltaL=+/-1%L- and DeltaE0=E|beta(n)|,
      E=0.1 meV, |beta(n)|<0.5, the new soliton is still stable. Therefore, the new
      solitons are quite robust against these nonuniform effects. However, they will be
      dispersed or disrupted in cases of very large structure nonuniformity. When the
      influence of temperature on solitons is considered, we find that the new solitons
      can transport steadily over 333 amino acid residues in the case of a long time
      period of 120 ps, in which the soliton can retain its shape and energy to travel
      forward along protein molecules after their mutual collision at the biological
      temperature of 300 K. However, the soliton disperses in cases of higher
      temperatures 325 K under action of a larger structure disorder. Thus, its
      critical temperature is about 320 K. When the effects of structure nonuniformity
      and temperature are considered simultaneously, then the new soliton has still
      high thermal stability and can transport also along the protein molecular chains
      retaining its amplitude, energy and velocity, they will disperses in the larger
      fluctuations, for example, 0.67 M-<M(k)<2M-, DeltaW=+/-6%W-, DeltaJ=+/-1.3%J-,
      Delta(chi1+chi2)=+/-2%(chi-1+chi-2), DeltaL=+/-1.5%L- and DeltaE0=E|beta(n)|,
      E=0.82 meV, |beta(n)|<=0.5 at T=300 K, or at higher temperatures 320 K and the
      fluctuations of 0.67M-<M(k)<2M-, Delta(chi1+chi2=+/-1%(chi-1+chi-2), DeltaJ=+/
      0.7%J-, DeltaW=+/-7%W-, DeltaL=+/-0.8%L- and DeltaE0=E|beta(n)|, E=0.4 meV,
      |beta(n)|<=0.5. These results mean that the critical temperature of the new
      soliton is 315K in this condition. Thus, we can conclude from these
      investigations that the new soliton is quite robust against the structure
      nonuniformities and thermal perturbation of proteins at 300 K in alpha-helix
      protein molecules, then it is a carrier of bio-energy transport and the improved
      model is a candidate for the mechanism of the bio-energy transport in the protein
      molecules. Finally we gave some experimental evidences for real existence of the
      soliton and validity of the theory of bio-energy transport in proteins.

PMID- 21951576
TI  - Screening of differentially expressed genes and predominant expression of beta
      variable region of T cell receptor in peripheral T cells of psoriatic patients.
AB  - Psoriasis is a skin disease featuring epithelial cell hyper-proliferation and T
      cell infiltration. Abnormal T cell immune responses play an important role in
      psoriatic pathogenesis. To screen differentially expressed genes in T cells of
      patients with plaque psoriasis, analyze the predominant expression of the beta
      variable region of T cell receptors and discuss the role of T cells in the
      pathogenesis of psoriasis. High throughput RNA sequencing and Real-time PCR were
      used. RESULTS: A total of 907 genes were differentially expressed in peripheral T
      cells of patients with psoriasis. Among them, 695 genes were mapped to the Gene
      Ontology database, 14 gene terms were significantly enriched, and 418 genes were
      involved in signaling pathways such as apoptosis, B cell receptor signaling and T
      cell receptor signaling. TRBV2, TRBV5-7, TRBV6-6/6-9, TRBV12, TRBV24 and TRBV29
      were significantly up-regulated in psoriatic patients compared to healthy
      subjects, among which, TRBV6-6/6-9, TRBV12 and TRBV29 are predominantly expressed
      in psoriatic patients. Many genes were differentially expressed in T cells of
      psoriatic patients, especially the TRBV gene family, which were predominantly
      expressed in T cells and might play an important role in abnormal immune
      responses of T cells in psoriatic patients.

PMID- 21951574
TI  - Kruppel-like factor 5 contributes to pulmonary artery smooth muscle proliferation
      and resistance to apoptosis in human pulmonary arterial hypertension.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is a vascular remodeling
      disease characterized by enhanced proliferation of pulmonary artery smooth muscle
      cell (PASMC) and suppressed apoptosis. This phenotype has been associated with
      the upregulation of the oncoprotein survivin promoting mitochondrial membrane
      potential hyperpolarization (decreasing apoptosis) and the upregulation of growth
      factor and cytokines like PDGF, IL-6 and vasoactive agent like endothelin-1 (ET
      1) promoting PASMC proliferation. Kruppel-like factor 5 (KLF5), is a zinc-finger
      type transcription factor implicated in the regulation of cell differentiation,
      proliferation, migration and apoptosis. Recent studies have demonstrated the
      implication of KLF5 in tissue remodeling in cardiovascular diseases, such as
      atherosclerosis, restenosis, and cardiac hypertrophy. Nonetheless, the
      implication of KLF5 in pulmonary arterial hypertension (PAH) remains unknown. We
      hypothesized that KLF5 up-regulation in PAH triggers PASMC proliferation and
      resistance to apoptosis. METHODS AND RESULTS: We showed that KFL5 is upregulated
      in both human lung biopsies and cultured human PASMC isolated from distal
      pulmonary arteries from PAH patients compared to controls. Using stimulation
      experiments, we demonstrated that PDGF, ET-1 and IL-6 trigger KLF-5 activation in
      control PASMC to a level similar to the one seen in PAH-PASMC. Inhibition of the
      STAT3 pathway abrogates KLF5 activation in PAH-PASMC. Once activated, KLF5
      promotes cyclin B1 upregulation and promotes PASMC proliferation and triggers
      survivin expression hyperpolarizing mitochondria membrane potential decreasing
      PASMC ability to undergo apoptosis. CONCLUSION: We demonstrated for the first
      time that KLF5 is activated in human PAH and implicated in the pro-proliferative
      and anti-apoptotic phenotype that characterize PAH-PASMC. We believe that our
      findings will open new avenues of investigation on the role of KLF5 in PAH and
      might lead to the identification of new therapeutic targets.

PMID- 21951577
TI  - Multimodality animal rotation imaging system (Mars) for in vivo detection of
      intraperitoneal tumors.
AB  - PROBLEM Ovarian cancer stem cells (OCSCs) have been postulated as the potential
      source of recurrence and chemoresistance. Therefore identification of OvCSC and
      their complete removal is a pivotal stage for the treatment of ovarian cancer.
      The objective of the following study was to develop a new in vivo imaging model
      that allows for the detection and monitoring of OCSCs. METHOD OF STUDY  OCSCs
      were labeled with X-Sight 761 Nanospheres and injected intra-peritoneally (i.p.)
      and sub-cutaneously (s.c.) to Athymic nude mice. The Carestream In-Vivo Imaging
      System FX was used to obtain X-ray and, concurrently, near-infrared fluorescence
      images. Tumor images in the mouse were observed from different angles by
      automatic rotation of the mouse. RESULTS  X-Sight 761 Nanospheres labeled almost
      100% of the cells. No difference on growth rate was observed between labeled and
      unlabeled cells. Tumors were observed and monitoring revealed strong signaling up
      to 21 days. CONCLUSION  We describe the use of near-infrared nanoparticle probes
      for in vivo imaging of metastatic ovarian cancer models. Visualization of
      multiple sites around the animals was enhanced with the use of the Carestream
      Multimodal Animal Rotation System.

PMID- 21951578
TI  - Purified Staphylococcus aureus leukotoxin LukM/F' does not trigger inflammation
      in the bovine mammary gland.
AB  - An early recruitment of neutrophils in mammary tissue and milk is considered an
      important component of the defense of the mammary gland against Staphylococcus
      aureus. We investigated whether the leukotoxin LukM/F', which is produced by a
      proportion of mastitis-causing strains of S. aureus, would be able to trigger
      inflammation in the udder. Infusion of purified LukM/F' toxin in lactating
      mammary glands did not cause neutrophil influx in milk, showing that the toxin
      was not able to cause mastitis on its own. Purified LukM/F' did not kill or
      stimulate mammary epithelial cells in culture. As expected, LukM bound to mammary
      macrophages and the complete LukM/F' toxin killed these cells, but subcytotoxic
      LukM/F' concentrations did not induce secretion of IL-8, TNF-alpha, IL-1beta or
      IL-6 by macrophages. On the contrary, the production of these pro-inflammatory
      mediators by adhesion-stimulated macrophages was reduced. Overall, these results
      indicate that purified leukotoxin LukM/F' is not likely to contribute to the
      initiation of the inflammatory response and could even play an anti-inflammatory
      role in the mammary gland by inactivating macrophages.

PMID- 21951579
TI  - Phytobezoar in a jejunal diverticulum as a cause of small bowel obstruction: a
      case report.
AB  - INTRODUCTION: Phytobezoars are concretions of poorly digested fruit and vegetable
      fibers found in the alimentary tract. Previous gastric resection,
      gastrojejunostomy, or pyloroplasty predispose people to bezoar formation. Small
      bowel bezoars normally come from the stomach, and primary small-bowel bezoars are
      very rare. They are seen only in patients with underlying small-bowel diseases
      such as diverticula, strictures, or tumors. Primary small-bowel bezoars almost
      always present as intestinal obstructions, although it is a very rare cause,
      being responsible for less than 3% of all small-bowel obstructions in one series.
      Jejunal diverticula are rare, with an incidence of less than 0.5%. They are
      usually asymptomatic pseudodiverticula of pulsion type, and complications are
      reported in 10% to 30% of patients. A phytobezoar in a jejunal diverticulum is an
      extremely rare presentation. CASE PRESENTATION: A 78-year-old Pakistani man
      presented to our clinic with small-bowel obstruction. Upon exploration, we found
      a primary small-bowel bezoar originating in a jejunal diverticulum and causing
      jejunal obstruction. Resection and anastomosis of the jejunal segment harboring
      the diverticulum was performed, and our patient had an uneventful recovery.
      CONCLUSION: Primary small-bowel bezoars are very rare but must be kept in mind as
      a possible cause of small-bowel obstruction.

PMID- 21951580
TI  - Predictors of sexual bother in a population of male North American medical
      students.
AB  - INTRODUCTION: The prevalence and associations of sexual bother in male medical
      students has not been extensively studied. AIMS: The aim of this study is to
      analyze predictors of sexual bother in a survey of male North American medical
      students. METHODS: Students enrolled in allopathic and osteopathic medical
      schools in North America between February 2008 and July 2008 were invited to
      participate in an internet-based survey of sexuality and sexual function. MAIN
      OUTCOME MEASURES: The principle outcome measure was a single-item question
      inquiring about global satisfaction with sexual function. The survey also
      consisted of a questionnaire that included ethnodemographic factors, student
      status, sexual history, and a validated scale for the assessment of depression.
      Respondents completed the International Index of Erectile Function, the premature
      ejaculation diagnostic tool, and the Self-Esteem and Relationship Quality survey
      (SEAR). Descriptive statistics, analysis of variance, and multivariable logistic
      regression were utilized to analyze responses. RESULTS: There were 480 male
      subjects (mean age 26.3 years) with data sufficient for analysis. Forty-three
      (9%) reported sexual bother. Sexual bother was significantly more common in men
      with erectile dysfunction (ED), high risk of premature ejaculation (HRPE),
      depressive symptoms, and lower sexual frequency. However, after multivariate
      analysis including SEAR scores, ED, and HRPE were no longer independently
      predictive of sexual bother. Higher scores for all domains of the SEAR were
      associated with lower odds of sexual bother. CONCLUSIONS: ED and HRPE are
      associated with sexual bother in this young and presumably healthy population.
      However, after controlling for relationship factors neither ED nor HRPE
      independently predicted sexual bother. It is plausible to hypothesize that sexual
      dysfunction from organic causes is rare in this population and is seldom
      encountered outside of relationship perturbations. Attention to relationship and
      psychological factors is likely of key importance in addressing sexual concerns
      in this population.

PMID- 21951581
TI  - Prophylaxis, preemption and drug resistance in CMV infection: too little, too
      much or just right?

PMID- 21951582
TI  - Gauzoma of the breast.

PMID- 21951583
TI  - Effect of IL-1beta and TNF-alpha vs IL-13 on bronchial hyperresponsiveness, beta2
      adrenergic responses and cellularity of bronchial alveolar lavage fluid.
AB  - 1 Levels of IL-13, IL-1beta and TNF-alpha are increased in bronchial lavage fluid
      of asthmatics and induce certain significant features of bronchial asthma
      including airway hyper-responsiveness (AHR). In this study, we have investigated
      the effect of these cytokines in naive mice and those sensitized to ovalbumin
      (OVA) on bronchoconstrictions to methacholine (MCh) and the functional antagonism
      induced by beta2 -adrenoceptor agonism. 2 Naive or OVA-sensitized mice were
      treated for 3 days with IL-1beta (250 U), TNF-alpha (150 ng), IL-13 (5 MUg) or
      combinations of IL-1beta with TNF-alpha or IL-1beta with IL-13. MCh-induced
      bronchoconstriction and its sensitivity to albuterol, a beta2-adrenoceptor
      agonist, was assessed 24 h after the last cytokine administration. 3 In naive
      mice, responsiveness to MCh was significantly increased by the combination of IL
      1beta and TNF-alpha, IL-13 alone or in combination with IL-1beta, but not by
      treatment with IL-1beta or TNF-alpha alone. Similar results were obtained in OVA
      sensitized mice except that treatment with IL-13 alone did not increase
      sensitivity to MCh. 4 In naive mice, albuterol sensitivity was only significantly
      attenuated by treatment with IL-1beta and TNF-alpha in combination. In mice
      sensitized to OVA, albuterol sensitivity was significantly attenuated by
      treatment with TNF-alpha, IL-13 or IL-13 in combination with IL-1beta. 5
      Inflammatory cell influx was increased by all cytokines and combinations except
      IL-13 in OVA-sensitized mice. 6 Our data do not support a link between
      inflammatory cell influx and AHR. In addition, the mechanism of IL-13-induced AHR
      might involve decreased beta2-adrenoceptor responsiveness.

PMID- 21951584
TI  - The effect of boric acid on acethylcholine, bethanechol and potasssium-evoked
      responses on ileum of rat.
AB  - 1 The aim of this study was to clarify the effect of boric acid on contractions
      of rat isolated ileum. 2 Contractile responses expressed as Emax and pD2 for
      acetylcholine (10(-3)-10(-8) m, Ach), bethanechol (10(-3)-10(-8) m) and potassium
      (10-80 * 10(-3) m, KCl) were determined in the absence and presence of boric acid
      (10(-3); 5 * 10(-4); 10(-4) m). 3 The contractile response to Ach in the presence
      of verapamil (10(-6) or 10(-8) m) or in calcium-free Tyrode's solution was also
      determined in the absence and presence of boric acid. 4 Boric acid did not affect
      the contractile response to Ach, bethanechol or KCl. Single or cumulative
      treatment of boric acid did not affect ileum muscle contraction evoked by KCl.
      The atropine-resistant component of Ach-induced contraction and 4-diphenyl
      acetoxy-N-methyl-piperidine methiodide-resistant component of bethanechol-induced
      contraction were not inhibited by boric acid (10(-3) m). The contractile response
      to Ach was reduced in calcium-free Tyrode's solution, and the contractile
      response was not affected by (10(-8) m). The addition of boric acid (10(-3) m) in
      combination with verapamil (10(-8) m) did not significantly affect the
      contractile response to Ach. 5 In conclusion, boric acid does not affect
      contractions induced by Ach, bethanechol or potassium in rat isolated ileum.

PMID- 21951585
TI  - Angiotensin II modifies the expression of alpha(1)-adrenoceptors in aorta smooth
      muscle cells of alpha(1D)-adrenoceptor knockout mice.
AB  - 1 The effect of angiotensin II (Ang II) on alpha(1A)-, alpha(1B)-, and a(1D)
      adrenoceptors (alpha(1)-AR) expression was analyzed in aorta smooth muscle cells
      obtained from wild-type (WT) and knock out of alpha(1D)-AR (alpha(1D)-AR KO)
      mice. 2 The relative abundance of mRNA for the three alpha(1)-ARs was determined
      in WT and alpha(1D)-AR KO aortic smooth muscle cells. There were no significant
      differences between WT and alpha(1D)-AR KO cells. 3 As early as 1 h Ang II
      increased alpha(1B)-AR mRNA in WT cells ~ 2 fold compared with control; in
      contrast, in alpha(1D)-AR KO cells the alpha(1B)-AR transcript was ~ 50% of
      control. 4 Western blot assays showed that Ang II incremented protein content for
      alpha(1A)-AR, 86% and 107% in WT and alpha(1D)-AR KO cells, respectively. 5
      Protein for alpha(1B)- and alpha(1D)-ARs did not change significantly with Ang II
      in both WT and a(1D)-AR KO cells. 6 The effect of Ang II on alpha(1B)-AR mRNA
      seems to be influenced by the absence of alpha(1D)-AR in aortic smooth muscle
      cells, which might be important to understand the interactions among alpha(1)
      ARs.

PMID- 21951587
TI  - Effect of biosynthetic intermediates and citrate on the phenyllactic and
      hydroxyphenyllactic acids production by Lactobacillus plantarum CRL 778.
AB  - AIM: To evaluate the influence of biosynthetic precursors, intermediates and
      electron acceptors on the production of antifungal compounds [phenyllactic acid
      (PLA) and hydroxyphenyllactic acid (OH-PLA)] by Lactobacillus plantarum CRL 778,
      a strain isolated from home-made sourdough. METHODS AND RESULTS: Growth of
      fermentative activity and antifungal compounds production by Lact. plantarum CRL
      778 were evaluated in a chemically defined medium (CDM) supplemented with
      biosynthetic precursors [phenylalanine (Phe), tyrosine (Tyr)], intermediates
      [glutamate (Glu), alpha-ketoglutarate (alpha-KG)] and electron acceptors [citrate
      (Cit)]. Results showed that the highest PLA production (0.26 mmol l(-1)), the
      main antifungal compound produced by Lact. plantarum CRL 778, occurred when
      greater concentrations of Phe than Tyr were present. Both PLA and OH-PLA yields
      were increased 2-folds when Cit was combined with alpha-KG instead of Glu at
      similar Tyr/Phe molar ratio. Similarly, glutamate dehydrogenase (GDH) activity
      was significantly (P < 0.01) stimulated by alpha-KG and Cit in Glu-free medium.
      CONCLUSION: Phe was the major stimulant for PLA formation; however, Cit could
      increase both PLA and OH-PLA synthesis by Lact. plantarum CRL 778 probably due to
      an increase in oxidized NAD(+). This effect, as well as the GDH activity, was
      enhanced by alpha-KG and down regulated by Glu. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This is the first study where the role of Glu and GDH activity in the PLA
      and OH-PLA synthesis was evidenced in sourdough lactic acid bacteria (LAB) using
      a CDM. These results contribute to the knowledge on the antifungal compounds
      production by sourdough LAB with potential applications on the baked goods.

PMID- 21951586
TI  - alpha(1D)-Adrenoceptor regulates the vasopressor action of alpha(1A)-adrenoceptor
      in mesenteric vascular bed of alpha(1D)-adrenoceptor knockout mice.
AB  - 1 The pressor action of the alpha(1A)-adrenoceptor (alpha(1A)-AR) agonist A61603
      (N-[5-(4,5-dihydro-1H-imidazol-2-yl)-2-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl]
      methanesulfonamide) and the alpha(1)-ARs agonist phenylephrine and their blockade
      by selective alpha(1)-ARs antagonists in the isolated mesenteric vascular bed of
      wild-type (WT) mice and alpha(1D)-AR knockout (KO alpha(1D)-AR) mice were
      evaluated. 2 The apparent potency of A61603 to increase the perfusion pressure in
      the mesenteric vascular bed of WT and KO alpha(1D)-AR mice is 86 and 138 times
      the affinity of phenylephrine, respectively. 3 A61603 also enhanced the perfusion
      pressure by ~1.7 fold in the mesenteric vascular bed of WT mice compared with KO
      alpha(1D)-AR mice. 4 Because of its high affinity, low concentrations of the
      alpha(1A)-AR selective antagonist RS100329 (5-methyl-3-[3-[4-[2-(2,2,2,
      trifluoroethoxy) phenyl]-1-piperazinyl] propyl]-2,4-(1H)-pyrimidinedione) shifted
      the agonist concentration-response curves to the right in the mesenteric vascular
      bed of WT and KO alpha(1D)-AR mice. 5 The alpha(1D)-AR selective antagonist
      BMY7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5] decane
      7,9-dione) did not modify the A61603 or the phenylephrine-induced pressor effect.
      6 The alpha(1B/D)-ARs alkylating antagonist chloroethylclonidine (CEC) shifted
      the agonist concentration-response curves to the right and decreased the maximum
      phenylephrine-induced vascular contraction in KO alpha(1D)-AR mice when compared
      to WT mice; however, CEC only slightly modified the contraction induced by
      A61603. 7 The results indicate that the isolated mesenteric vascular bed of WT
      and KO alpha(1D)-AR mice expresses alpha(1A)-AR, that the pressor action of
      alpha(1A)-AR is up-regulated for alpha(1D)-AR in WT mice and suggest an important
      role of alpha(1B)-AR in the vascular pressure evoked by phenylephrine in KO
      alpha(1D)-AR mice.

PMID- 21951588
TI  - Replication efficiency of oncolytic vaccinia virus in cell cultures
      prognosticates the virulence and antitumor efficacy in mice.
AB  - BACKGROUND: We have shown that insertion of the three vaccinia virus (VACV)
      promoter-driven foreign gene expression cassettes encoding Renilla luciferase
      Aequorea GFP fusion protein, beta-galactosidase, and beta-glucuronidase into the
      F14.5L, J2R, and A56R loci of the VACV LIVP genome, respectively, results in a
      highly attenuated mutant strain GLV-1h68. This strain shows tumor-specific
      replication and is capable of eradicating tumors with little or no virulence in
      mice. This study aimed to distinguish the contribution of added VACV promoter
      driven transcriptional units as inserts from the effects of insertional
      inactivation of three viral genes, and to determine the correlation between
      replication efficiency of oncolytic vaccinia virus in cell cultures and the
      virulence and antitumor efficacy in mice METHODS: A series of recombinant VACV
      strains was generated by replacing one, two, or all three of the expression
      cassettes in GLV-1h68 with short non-coding DNA sequences. The replication
      efficiency and tumor cell killing capacity of these newly generated VACV strains
      were compared with those of the parent virus GLV-1h68 in cell cultures. The virus
      replication efficiency in tumors and antitumor efficacy as well as the virulence
      were evaluated in nu/nu (nude) mice bearing human breast tumor xenografts.
      RESULTS: we found that virus replication efficiency increased with removal of
      each of the expression cassettes. The increase in virus replication efficiency
      was proportionate to the strength of removed VACV promoters linked to foreign
      genes. The replication efficiency of the new VACV strains paralleled their
      cytotoxicity in cell cultures. The increased replication efficiency in tumor
      xenografts resulted in enhanced antitumor efficacy in nude mice. Similarly, the
      enhanced virus replication efficiency was indicative of increased virulence in
      nude mice. CONCLUSIONS: These data demonstrated that insertion of VACV promoter
      driven transcriptional units into the viral genome for the purpose of insertional
      mutagenesis did modulate the efficiency of virus replication together with
      antitumor efficacy as well as virulence. Replication efficiency of oncolytic VACV
      in cell cultures can predict the virulence and therapeutic efficacy in nude mice.
      These findings may be essential for rational design of safe and potent VACV
      strains for vaccination and virotherapy of cancer in humans and animals.

PMID- 21951589
TI  - Protein trafficking rates assessed by quantum dot quenching with bromocresol
      green.
AB  - Quantum dots are bright, photostable fluorophores used extensively to investigate
      biological processes. In this study, we report that bromocresol green (BCG) at
      low micromolar concentrations rapidly, efficiently and reversibly quenches the
      fluorescence of commercial quantum dots having a wide range of functionalities.
      The broad utility of BCG quenching of quantum dots in cell biology is showed in
      quantitative assays of trafficking of the beta(2) -adrenergic receptor (beta(2)
      AR) and the cystic fibrosis transmembrane conductance regulator (CFTR).

PMID- 21951590
TI  - An IkappaB kinase 2 inhibitor IMD-0354 suppresses the survival of adult T-cell
      leukemia cells.
AB  - Adult T-cell leukemia (ATL) is a fatal T-cell malignancy associated with human T
      cell leukemia virus type I infection. The aberrant expression of nuclear factor
      kappaB (NF-kappaB) is considered to contribute to the malignant phenotype and
      chemo-resistance of ATL cells. Because of the poor prognosis of ATL, the
      development of new therapeutic strategies is direly needed. In the present study,
      we show that an IkappaB kinase 2 (IKK2) inhibitor, IMD-0354, efficiently inhibits
      the survival of CD4(+) CD25(+) primary ATL cells and prevents the growth of or
      induces apoptosis of patient-derived ATL cell lines. Assays of transcription with
      integrated forms of reporter genes revealed that IMD-0354 suppresses NF-kappaB
      dependent transcriptional activity. Moreover, the daily administration of IMD
      0354 prevents the growth of tumors in mice inoculated with ATL cells. Our results
      suggest that targeting IKK2 with a small molecule inhibitor, such as IMD-0354, is
      an attractive strategy for the treatment of ATL.

PMID- 21951591
TI  - Motor performance in chronic low back pain: is there an influence of pain-related
      cognitions? A pilot study.
AB  - BACKGROUND: Chronic low back pain (CLBP) is often accompanied by an abnormal
      motor performance. However, it has not been clarified yet whether these
      deviations also occur during motor tasks not involving the back and whether the
      performance is influenced by pain and pain-related cognitions. Therefore, the aim
      of the present study is to get insight in the contribution of both pain
      experience and pain-related cognitions to general motor task performance in CLBP.
      METHODS: 13 CLBP patients and 15 healthy subjects performed a hand-function task
      in three conditions: sitting, lying prone (lying) and lying prone without trunk
      support (provoking). The last condition was assumed to provoke pain-related
      cognitions, which was considered successful when a patients' pain expectancy on a
      numeric rating scale was at least 1 point higher than actual pain experienced.
      Subjects' performance was expressed in reaction time and movement time. Repeated
      measures analysis of variance was performed to detect main effect for group and
      condition. Special interest was given to group*condition interaction, since
      significant interaction would indicate that patients and healthy subjects
      performed differently throughout the three conditions. RESULTS: Patients were
      slower throughout all conditions compared to healthy subjects. With respect to
      the provoking condition, patients showed deteriorated performance compared to
      lying while healthy subjects' performance remained equal between these two
      conditions. Further analysis of patients' data showed that provocation was
      successful in 54% of the patients. Especially this group showed deteriorated
      performance in the provoking condition. CONCLUSION: It can be concluded that CLBP
      patients in general have worse motor task performance compared to healthy
      subjects and that provoking pain-related cognitions further worsened performance.

PMID- 21951592
TI  - Scuba diving by patients with haemophilia: a few notes of precaution.

PMID- 21951593
TI  - Transcriptomics of environmental acclimatization and survival in wild adult
      Pacific sockeye salmon (Oncorhynchus nerka) during spawning migration.
AB  - Environmental shifts accompanying salmon spawning migrations from ocean feeding
      grounds to natal freshwater streams can be severe, with the underlying stress
      often cited as a cause of increased mortality. Here, a salmonid microarray was
      used to characterize changes in gene expression occurring between ocean and river
      habitats in gill and liver tissues of wild migrating sockeye salmon (Oncorhynchus
      nerka Walbaum) returning to spawn in the Fraser River, British Columbia, Canada.
      Expression profiles indicate that the transcriptome of migrating salmon is
      strongly affected by shifting abiotic and biotic conditions encountered along
      migration routes. Conspicuous shifts in gene expression associated with changing
      salinity, temperature, pathogen exposure and dissolved oxygen indicate that these
      environmental variables most strongly impact physiology during spawning
      migrations. Notably, transcriptional changes related to osmoregulation were
      largely preparatory and occurred well before salmon encountered freshwater. In
      the river environment, differential expression of genes linked with elevated
      temperatures indicated that thermal regimes within the Fraser River are
      approaching tolerance limits for adult salmon. To empirically correlate gene
      expression with survival, biopsy sampling of gill tissue and transcriptomic
      profiling were combined with telemetry. Many genes correlated with environmental
      variables were differentially expressed between premature mortalities and
      successful migrants. Parametric survival analyses demonstrated a broad-scale
      transcriptional regulator, cofactor required for Sp1 transcriptional activation
      (CRSP), to be significantly predictive of survival. As the environmental
      characteristics of salmon habitats continue to change, establishing how current
      environmental conditions influence salmon physiology under natural conditions is
      critical to conserving this ecologically and economically important fish species.

PMID- 21951594
TI  - Reversible control of biofilm formation by Cellulomonas spp. in response to
      nitrogen availability.
AB  - The microbial degradation of cellulose contributes greatly to the cycling of
      carbon in terrestrial environments and feedbacks to the atmosphere, a process
      that is highly responsive to nitrogen inputs. Yet how key groups of cellulolytic
      microorganisms adaptively respond to the global conditions of nitrogen limitation
      and/or anthropogenic or climate nitrogen inputs is poorly understood. The
      actinobacterial genus Cellulomonas is of special interest because it incorporates
      the only species known to degrade cellulose aerobically and anaerobically.
      Furthermore, despite their inability to fix nitrogen, they are active decomposers
      in nitrogen-limited environments. Here we show that nitrogen limitation induced
      biofilm formation in Cellulomonas spp., a process that was coupled to carbon
      sequestration and storage in a curdlan-type biofilm matrix. The response was
      reversible and the curdlan matrix was solubilized and used as a carbon and energy
      source for biofilm dispersal once nitrogen sources became available. The biofilms
      attached strongly to cellulosic surfaces and, despite the growth limitation,
      produced cellulases and degraded cellulose more efficiently. The results show
      that biofilm formation is a competitive strategy for carbon and nitrogen
      acquisition and provide valuable insights linking nitrogen inputs to carbon
      sequestration and remobilization in terrestrial environments.

PMID- 21951595
TI  - British HIV Association guidelines for the treatment of TB/HIV coinfection 2011.

PMID- 21951596
TI  - HIV antiretroviral therapy reduces circulating surfactant protein-D levels.

PMID- 21951597
TI  - The role of antimalarial treatment in the elimination of malaria.
AB  - With declining transmission of malaria in several regions of the world and
      renewed interest in the elimination of malaria, strategies for malaria control
      using antimalarial drugs are being revisited. Drug-based strategies to reduce
      transmission of malaria need to target the asymptomatic carriers of infection.
      Drugs that are effective against gametocytes are few in number, but it may be
      possible to reduce gametocyte production by killing the asexual stages, for which
      more drugs are available. Drugs for use in large-scale programmes must be safe
      and tolerable. Strategies include improving access to treatment for malaria with
      an efficacious drug, intermittent-treatment programmes, and mass drug
      administration, with and without screening for malaria. Recent proposals have
      targeted high-risk groups for interventions. None of the strategies has been
      rigorously tested with appropriate control groups for comparison. Because of the
      lack of field evidence, modelling has been used. Models have shown, first, that
      for long-lasting effects, drug administration programmes should be linked with
      vector control, and second, that if elimination is the aim, programmes are likely
      to be more successful when applied to smaller populations of a few thousand or
      less. In order to sustain the gains following the scaling up of vector control
      and use of artemisinin combination therapies (ACTs), strategies that use
      antimalarials effectively need to be devised and evidence generated for the most
      cost-efficient way forward.

PMID- 21951598
TI  - Permanent Genetic Resources added to Molecular Ecology Resources Database 1 June
      2011-31 July 2011.
AB  - This article documents the addition of 112 microsatellite marker loci and 24
      pairs of single nucleotide polymorphism (SNP) sequencing primers to the Molecular
      Ecology Resources Database. Loci were developed for the following species:
      Agelaius phoeniceus, Austrolittorina cincta, Circus cyaneus, Circus macrourus,
      Circus pygargus, Cryptocoryne * purpurea Ridl. nothovar. purpurea, Mya arenaria,
      Patagioenas squamosa, Prochilodus mariae, Scylla serrata and Scytalopus
      speluncae. These loci were cross-tested on the following species: Cryptocoryne *
      purpurea nothovar. purpurea, Cryptocoryne affinis, Cryptocoryne ciliata,
      Cryptocoryne cordata var. cordata, Cryptocoryne elliptica, Cryptocoryne
      griffithii, Cryptocoryne minima, Cryptocoryne nurii and Cryptocoryne schulzei.
      This article also documents the addition of 24 sequencing primer pairs and 24
      allele-specific primers or probes for Aphis glycines.

PMID- 21951599
TI  - Evidence for protein-mediated fatty acid efflux by adipocytes.
AB  - AIM: The hormonally controlled mobilization and release of fatty acids from
      adipocytes into the circulation is an important physiological process required
      for energy homeostasis. While uptake of fatty acids by adipocytes has been
      suggested to be predominantly protein-mediated, it is unclear whether the efflux
      of fatty acids also requires membrane proteins. METHODS: We used fluorescent
      fatty acid efflux assays and colorimetric assays for free fatty acids and
      glycerol to identify inhibitors with effects on fatty acid efflux, but not
      lipolysis, in 3T3-L1 adipocytes. We assessed the effect of these inhibitors on a
      fibroblast-based cell line expressing fatty acid transport protein 1, hormone
      sensitive lipase and perilipin, which presumably lacks adipocyte-specific
      proteins for fatty acid efflux. RESULTS: We identified 4,4'
      diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) as an inhibitor of fatty
      acid efflux that did not impair lipolysis or the cellular exit of glycerol but
      lead to an accumulation of intracellular fatty acids. In contrast, fatty acid
      efflux by the reconstituted cellular model for fatty acid efflux was responsive
      to lipolytic stimuli, but insensitive to DIDS inhibition. CONCLUSION: We propose
      that adipocytes specifically express an as yet unidentified DIDS-sensitive
      protein that enhances the efflux of fatty acids and therefore may lead to novel
      treatment approaches for obesity-related disorders characterized by abnormal
      lipid fluxes and ectopic triglyceride accumulation.

PMID- 21951600
TI  - Discovering biological connections between experimental conditions based on
      common patterns of differential gene expression.
AB  - BACKGROUND: Identifying similarities between patterns of differential gene
      expression provides an opportunity to identify similarities between the
      experimental and biological conditions that give rise to these gene expression
      alterations. The growing volume of gene expression data in open data repositories
      such as the NCBI Gene Expression Omnibus (GEO) presents an opportunity to
      identify these gene expression similarities on a large scale across a diverse
      collection of datasets. We have developed a fast, pattern-based computational
      approach, named openSESAME (Search of Expression Signatures Across Many
      Experiments), that identifies datasets enriched in samples that display
      coordinate differential expression of a query signature. Importantly, openSESAME
      performs this search without prior knowledge of the phenotypic or experimental
      groups in the datasets being searched. This allows openSESAME to identify
      perturbations of gene expression that are due to phenotypic attributes that may
      not have been described in the sample annotation included in the repository. : To
      demonstrate the utility of openSESAME, we used gene expression signatures of two
      biological perturbations to query a set of 75,164 human expression profiles that
      were generated using Affymetrix microarrays and deposited in GEO. The first
      query, using a signature of estradiol treatment, identified experiments in which
      estrogen signaling was perturbed and also identified differences in estrogen
      signaling between estrogen receptor-positive and -negative breast cancers. The
      second query, which used a signature of silencing of the transcription factor p63
      (a key regulator of epidermal differentiation), identified datasets related to
      stratified squamous epithelia or epidermal diseases such as melanoma.
      CONCLUSIONS: openSESAME is a tool for leveraging the growing body of publicly
      available microarray data to discover relationships between different biological
      states based on common patterns of differential gene expression. These
      relationships may serve to generate hypotheses about the causes and consequences
      of specific patterns of observed differential gene expression.

PMID- 21951601
TI  - Pretreatment with Delta9-tetrahydrocannabinol (THC) increases cocaine-stimulated
      activity in adolescent but not adult male rats.
AB  - Marijuana (Cannabis sativa) remains one of the most widely used illegal drugs,
      with adolescents being particularly vulnerable to its use and abuse. In spite of
      this, most studies are conducted in adult animals even though the effects might
      be quite different in adolescents. Additionally, the use of marijuana often
      precedes the use of other psychoactive drugs including cocaine, especially when
      marijuana exposure begins during early adolescence. The purpose of this study was
      to examine the effects of repeated Delta9-tetrahydrocannabinol (THC), the major
      active ingredient in marijuana, in adolescents compared to adults and to
      determine its subsequent effects on cocaine-stimulated activity. To this end,
      adolescent (postnatal day PND 34) and adult (PND 66) rats were administered 3
      mg/kg/day THC for 8 days and locomotor activity was measured on days 1, 2, 7 and
      8 after dosing. On day 12 (4 days after the last dose of THC), rats were injected
      with escalating doses of cocaine and behavior was recorded. Results show that THC
      depressed locomotor activity in adult rats but not in adolescents. However,
      following a cocaine challenge, adolescents exposed to THC showed increased
      locomotor responses to cocaine compared to chronic vehicle-injected controls.
      This was not seen in adults. These results show that the effects of cocaine are
      enhanced after THC in adolescents, but not adults, and that this might account
      for the greater transition to cocaine after early, as opposed to later, marijuana
      use.

PMID- 21951602
TI  - On the trail of the glucocorticoid receptor: into the nucleus and back.
AB  - The glucocorticoid receptor (GR) belongs to the superfamily of steroid receptors
      and is an important regulator of physiological and metabolic processes. In its
      inactive state, GR is unbound by ligand and resides in the cytoplasm in a
      chaperone complex. When it binds glucocorticoids, it is activated and
      translocates to the nucleus, where it functions as a transcription factor.
      However, the subcellular localization of GR is determined by the balance between
      its rates of nuclear import and export. The mechanism of GR nuclear transport has
      been extensively studied. Originally, it was believed that nuclear import of GR
      is initiated by dissociation of the chaperone complex in the cytoplasm. However,
      several studies show that the chaperone machinery is required for nuclear
      transport of GR. In this review, we summarize the contribution of various
      chaperone components involved in the nuclear transport of GR and propose an
      updated model of its nuclear import and export. Moreover, we review the
      importance of ligand-independent nuclear transport and compare the nuclear
      transport of GR with that of other steroid receptors.

PMID- 21951603
TI  - Sphingosylphosphorylcholine induces stress fiber formation via activation of Fyn
      RhoA-ROCK signaling pathway in fibroblasts.
AB  - Sphingosylphosphorylcholine (SPC), a bioactive sphingolipid, has recently been
      reported to modulate actin cytoskeleton rearrangement. We have previously
      demonstrated Fyn tyrosine kinase is involved in SPC-induced actin stress fiber
      formation in fibroblasts. However, Fyn-dependent signaling pathway remains to be
      elucidated. The present study demonstrates that RhoA-ROCK signaling downstream of
      Fyn controls stress fiber formation in SPC-treated fibroblasts. Here, we found
      that SPC-induced stress fiber formation was inhibited by C3 transferase, dominant
      negative RhoA or ROCK. SPC activated RhoA, which was blocked by pharmacological
      inhibition of Fyn activity or dominant negative Fyn. Constitutively active Fyn
      (ca-Fyn) stimulated stress fiber formation and localized with F-actin at the both
      ends of stress fibers, both of which were prevented by Fyn translocation
      inhibitor eicosapentaenoic acid (EPA). In contrast, inhibition of ROCK abolished
      only the formation of stress fibers, without affecting the localization of ca
      Fyn. These results allow the identification of the molecular events downstream
      SPC in stress fiber formation for a better understanding of stress fiber
      formation involving Fyn.

PMID- 21951605
TI  - T-cell receptor gene therapy targeting melanoma-associated antigen-A4 inhibits
      human tumor growth in non-obese diabetic/SCID/gammacnull mice.
AB  - Adoptive cell therapy with lymphocytes that have been genetically engineered to
      express tumor-reactive T-cell receptors (TCR) is a promising approach for cancer
      immunotherapy. We have been exploring the development of TCR gene therapy
      targeting cancer/testis antigens, including melanoma-associated antigen (MAGE)
      family antigens, that are ideal targets for adoptive T-cell therapy. The efficacy
      of TCR gene therapy targeting MAGE family antigens, however, has not yet been
      evaluated in vivo. Here, we demonstrate the in vivo antitumor activity in
      immunodeficient non-obese diabetic/SCID/gammac(null) (NOG) mice of human
      lymphocytes genetically engineered to express TCR specific for the MAGE-A4
      antigen. Polyclonal T cells derived from human peripheral blood mononuclear cells
      were transduced with the alphabeta TCR genes specific for MAGE-A4, then
      adoptively transferred into NOG mice inoculated with MAGE-A4 expressing human
      tumor cell lines. The transferred T cells maintained their effector function in
      vivo, infiltrated into tumors, and inhibited tumor growth in an antigen-specific
      manner. The combination of adoptive cell therapy with antigen peptide vaccination
      enhanced antitumor activity, with improved multifunctionality of the transferred
      cells. These data suggest that TCR gene therapy with MAGE-A4-specific TCR is a
      promising strategy to treat patients with MAGE-A4-expressing tumors; in addition,
      the acquisition of multifunctionality in vivo is an important factor to predict
      the quality of the T-cell response during adoptive therapy with human
      lymphocytes.

PMID- 21951604
TI  - EGF receptor inhibitors increase ErbB3 mRNA and protein levels in breast cancer
      cells.
AB  - The potential benefits of drugs directly targeting the ErbB receptors for cancer
      therapy have led to an extensive development within this field. However, the
      clinical effects of ErbB receptor-targeting drugs in cancer treatment are limited
      due to a high frequency of resistance. It has been reported that, when inhibiting
      the epidermal growth factor receptor (EGFR) with the tyrosine kinase inhibitor
      gefitinib, increased activation of ErbB3 via MET, or by re-localization of ErbB3
      mediates cell survival. Here we show further evidence that members of the ErbB
      receptor family facilitate resistance to EGFR inhibitor treatment in ErbB2
      overexpressing breast cancer cells. We found that gefitinib treatment increased
      ErbB3 expression, both at protein and mRNA levels. ErbB3 expression was
      upregulated not only by gefitinib but also by a panel of different EGFR
      inhibitors, suggesting that inhibition of EGFR in general affects ErbB3
      expression. In addition, we found that gefitinib treatment increased ErbB2
      expression levels while EGFR inhibitors decreased the activity of ErbB2.
      Concentrations of gefitinib that decreased phospho-ErbB2 reversely increased
      ErbB3 levels. We further examined changes induced by gefitinib treatment on mRNA
      levels of the most common genes known to be involved in breast cancer. As
      expected, we found that gefitinib downregulated genes whose functions were linked
      to cellular proliferation, such as Ki-67, topoisomerase II alpha and cyclins, and
      surprisingly downregulated gene expression of FAS which is involved in apoptotic
      signaling. Together, our data strongly suggest that resistance to EGFR inhibitors
      may result from the compensation of other family members and that combinations of
      anti-cancer drugs are required to increase the sensitivity of these treatments.

PMID- 21951606
TI  - EHEC/EAEC O104:H4 strain linked with the 2011 German outbreak of haemolytic
      uremic syndrome enters into the viable but non-culturable state in response to
      various stresses and resuscitates upon stress relief.
AB  - Various non-spore forming bacteria, including Escherichia coli, enter a dormant
      like state, the viable but non-culturable (VBNC) state, characterized by the
      presence of viable cells but the inability to grow on routine laboratory media.
      Upon resuscitation, these VBNC cells recover both culturability and
      pathogenicity. In 2011, a large outbreak involving more than 3000 cases of bloody
      diarrhoea and haemolytic uremic syndrome was caused by an E. coli O104:H4 strain
      expressing genes characteristic of both enterohaemorrhagic (EHEC) and
      enteroaggregative E. coli (EAEC). The ability of the outbreak strain to enter the
      VBNC state may have complicated its detection in the suspected sources. In this
      paper, we investigated the ability of the outbreak strain to enter and
      subsequently recover from the VBNC state. We found that in a nutrient-poor micro
      environment, various stresses such as toxic concentrations of copper ions or
      certain types of tap water are able to render the bacteria unculturable within a
      few days. Without copper ion stress, the majority of cells remained culturable
      for at least 40 days. Incubation with the stressors at 23 degrees C compared with
      4 degrees C hastened this observed loss of culturability. The integrity of a
      considerable fraction of copper ion- and tap water 1-stressed bacteria was
      demonstrated by live/dead staining and microscopy. Relieving stress by copper-ion
      chelation facilitated resuscitation of these bacteria while preserving their
      fitness, major virulence gene markers (stx2, aggR, aggA genes) and specific
      phenotypes (ESBL resistance, autoaggregation typical for EAEC strains).

PMID- 21951608
TI  - Atypical endosalpingiosis in axillary sentinel lymph node: a potential source of
      false-positive diagnosis of metastasis.

PMID- 21951607
TI  - The role of amputation as an outcome measure in cellular therapy for critical
      limb ischemia: implications for clinical trial design.
AB  - BACKGROUND: Autologous bone marrow-derived stem cells have been ascribed an
      important therapeutic role in No-Option Critical limb Ischemia (NO-CLI). One
      primary endpoint for evaluating NO-CLI therapy is major amputation (AMP), which
      is usually combined with mortality for AMP-free survival (AFS). Only a trial
      which is double blinded can eliminate physician and patient bias as to the timing
      and reason for AMP. We examined factors influencing AMP in a prospective double
      blinded pilot RCT (2:1 therapy to control) of 48 patients treated with site of
      service obtained bone marrow cells (BMAC) as well as a systematic review of the
      literature. METHODS: Cells were injected intramuscularly in the CLI limbs as
      either BMAC or placebo (peripheral blood). Six month AMP rates were compared
      between the two arms. Both patient and treating team were blinded of the
      assignment in follow-up examinations. A search of the literature identified 9 NO
      CLI trials, the control arms of which were used to determine 6 month AMP rates
      and the influence of tissue loss. RESULTS: Fifteen amputations occurred during
      the 6 month period, 86.7% of these during the first 4 months. One amputation
      occurred in a Rutherford 4 patient. The difference in amputation rate between
      patients with rest pain (5.6%) and those with tissue loss (46.7%), irrespective
      of treatment group, was significant (p = 0.0029). In patients with tissue loss,
      treatment with BMAC demonstrated a lower amputation rate than placebo (39.1% vs.
      71.4%, p = 0.1337). The Kaplan-Meier time to amputation was longer in the BMAC
      group than in the placebo group (p = 0.067). Projecting these results to a
      pivotal trial, a bootstrap simulation model showed significant difference in AFS
      between BMAC and placebo with a power of 95% for a sample size of 210 patients.
      Meta-analysis of the literature confirmed a difference in amputation rate between
      patients with tissue loss and rest pain. CONCLUSIONS: BMAC shows promise in
      improving AMP-free survival if the trends in this pilot study are validated in a
      larger pivotal trial. The difference in amp rate between Rutherford 4 & 5
      patients suggests that these patients should be stratified in future RCTs.

PMID- 21951609
TI  - Commentary: one small step.

PMID- 21951610
TI  - The prevalence of transitional vertebrae in the lumbar spine.
AB  - BACKGROUND CONTEXT: Lumbosacral transitional vertebrae (LSTVs) are a congenital
      vertebral anomaly of the L5-S1 junction in the spine. This alteration may
      contribute to incorrect identification of a vertebral segment, leading to wrong
      level spine surgery and poor correlation with clinical symptoms. Although several
      studies describe the occurrence of this anomaly in back pain populations,
      investigation of the prevalence in the American general population is lacking.
      PURPOSE: To establish the prevalence rates for LSTVs in the general population.
      STUDY DESIGN: Retrospective review. PATIENT SAMPLE: Consecutive kidney-urinary
      bladder (KUB) radiographs of subjects from the past 2 years (2008-2009). OUTCOME
      MEASURES: Clinical demographics, number of lumbar vertebrae, L5-S1 transverse
      process (TP) height, and rib length. METHODS: Consecutive adult KUB studies of
      adult subjects were queried with clear visibility of the last rib's vertebral
      body articulation, all lumbar TPs, and complete sacral wings. Exclusion criteria
      consisted of any radiologic evidence of previous lumbosacral surgery that would
      obstruct our measurements. A total of 1,100 abdominal films were reviewed, and
      211 were identified as being adequate for the measurement of the desired
      parameters. RESULTS: Two hundred eleven subjects were identified as eligible for
      the study, and 75 (35.6%) were classified as positive for a transitional
      lumbosacral vertebra. The most common anatomical variant was the Castellvi Type
      IA (14.7%). The average age at the time of the KUB study was 59.8 years (18-95
      years). One hundred ninety-seven subjects (93.4%) presented five lumbar
      (nonribbed) vertebrae, and only 14 (6.6%) had six lumbar vertebrae. CONCLUSIONS:
      The significance of lumbosacral transitional level changes to the establishment
      of pain, degenerative changes, stenosis, and disc disease have been well
      documented in symptomatic patients. Although LSTV's role in low back pain remains
      controversial, our study has shown that, when the same criteria are used for
      classification, prevalence among the general population and symptomatic patients
      may be similar.

PMID- 21951611
TI  - Commentary: surgical management of thoracolumbar neurologic injuries.

PMID- 21951612
TI  - Commentary: "minimally invasive corpectomy and posterior stabilization for lumbar
      burst fracture".

PMID- 21951613
TI  - Response of Lactobacillus casei BL23 to phenolic compounds.
AB  - AIMS: To determine the inhibitory effect of phenolic compounds on Lactobacillus
      casei BL23, the role of two component signal transduction systems (TCS) and the
      response of Lact. casei BL23 to p-coumaric acid. METHODS AND RESULTS: Growth of
      Lact. casei BL23 and 17 derivative strains defective in each TCS harboured by
      this strain in the presence of p-coumaric acid, ferulic acid, caffeic acid or
      methyl gallate was monitored. Furthermore, changes in the protein content of
      Lact. casei BL23 when exposed to p-coumaric acid were evaluated by 2D-SDS-PAGE.
      Eleven proteins differentially expressed in the presence of p-coumaric acid were
      detected. Six of them could be identified: ClpP and HtrA, involved in protein
      turnover and folding, acetyl-CoA carboxylase, involved in lipid metabolism, and
      an arginyl-tRNA synthetase were more abundant, whereas PurL and PurN, involved in
      purine biosynthesis, were less abundant. CONCLUSIONS: No significant differences
      were observed between the parental strain and the TCS-defective mutants. p
      Coumaric acid elicited a response against membrane and cytoplasmic damages.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The inhibitory effect of phenolic compounds
      on Lact. casei BL23 has been determined. For the first time, cytoplasmic proteins
      presumably involved in the response of Lact. casei BL23 against p-coumaric acid
      have been identified.

PMID- 21951614
TI  - A novel method for screening a vertebrate transcriptome for genes involved in
      carotenoid binding and metabolism.
AB  - Carotenoid-based colour signals are widespread in the animal kingdom and common
      textbook examples of sexually selected traits. Carotenoid pigments must be
      obtained through the diet as all animals lack the enzymatic machinery necessary
      to synthesize them from scratch. Once ingested, carotenoids are metabolized,
      stored, transported and deposited, and some or all of these processes may be
      limiting for signal production and thus subjected to social or sexual selection
      on phenotypic coloration. Very little is known about which genes and
      physiological pathways are involved in carotenoid pigmentation which is
      unfortunate, as genetic information would allow us to investigate the biochemical
      consequences of sexual selection. In this study, we present a transcriptome
      screening technique and apply it to a carotenoid-signalling bird species, the
      southern red bishop Euplectes orix, to uncover the gene(s) responsible for the
      conversion of dietary beta-carotene (orange) to canthaxanthin (bright red). The
      transcriptome, extracted from the liver of a male entering his breeding moult, is
      expressed within bacterial cells genetically modified to synthesize beta
      carotene. Effects of expressed E. orix proteins on the structure or amount of
      beta-carotene are initially detected by eye (based on colour change) and
      subsequently confirmed by high-performance liquid chromatography. Here, we
      demonstrate the validity of the technique and provide a list of candidate genes
      involved in the carotenoid pigmentation pathway. We believe that this method
      could be applied to other species and tissues and that this may help researchers
      uncover the genetic basis of carotenoid coloration in vertebrates.

PMID- 21951615
TI  - Alteration in N-glycomics during mouse aging: a role for FUT8.
AB  - We recently reported that N-glycosylation changes during human aging. To further
      investigate the molecular basis determining these alterations, the aging process
      in mice was studied. N-glycan profiling of mouse serum glycoproteins in different
      age groups of healthy C57BL/6 mice showed substantial age-related changes in
      three major N-glycan structures: under-galactosylated biantennary (NGA2F),
      biantennary (NA2), and core alpha-1,6-fucosylated -beta-galactosylated
      biantennary structures (NA2F). Mice defective in klotho gene expression (kl/kl),
      which have a shortened lifespan, displayed a similar but accelerated trend.
      Interestingly, the opposite trend was observed in slow-aging Snell Dwarf mice
      (dw/dw) and in mice fed a calorically restricted diet. We also discovered that
      increased expression and activity of alpha-1,6-fucosyltransferase (FUT8) in the
      liver are strongly linked to the age-related changes in glycosylation and that
      this increased FUT8 and fucosylation influence IGF-1 signaling. These data
      demonstrate that the glycosylation machinery in liver cells is significantly
      affected during aging and that age-related increased FUT8 activity could
      influence the aging process by altering the sensitivity of the IGF-1R signaling
      pathway.

PMID- 21951616
TI  - The impact of systemic lupus erythematosus on women's sexual functioning.
AB  - INTRODUCTION: The effect of systemic lupus erythematosus (SLE) on women's sexual
      functioning has been rarely assessed. AIM: The aim of this study is to evaluate
      the impact of SLE on women's sexual functioning. METHODS: A total of 302
      consecutive female outpatients with SLE were provided with a questionnaire
      composed of the Female Sexual Function Index (FSFI), questions for
      sociodemographic characteristics and comorbidities. Similarly, 2,159 hospital
      female employees were assessed as the control group. In patients, data of SLE
      duration and Sjogren's syndrome were derived from the chart records and the
      disease activity was assessed using the SLE Disease Activity Index 2000. MAIN
      OUTCOME MEASURES: The FSFI scores were compared between the patients and the
      controls. Correlates of the FSFI scores were determined in the patients. RESULTS:
      Of 302 eligible patients, 92.4% (279/302) responded, in addition to 73.2%
      (1,580/2,159) of controls. Ninety-five percent (255/268) of the respondent
      patients were in no-to-mild SLE disease activity. Among the respondents, 171
      (61.3%) patients and 930 (58.9%) controls were sexually active in the previous
      month, P = 0.446. Of the sexually active patients, 52.5% (85/162) had impaired
      sexual function (the FSFI total score < 26.55) and so did 47.1% (408/867) of the
      sexually active controls, P = 0.206. With adjustment of age group, marital status
      and education level, patients had lower FSFI scores than controls only in the
      domains of lubrication and pain. Significant risk factors for lower FSFI scores
      in the patients included persistent activity or flare of SLE, menstrual cycle
      disturbances, and vascular disease. With further adjustment of other risk
      factors, only vascular disease remained significant as a risk factor for impaired
      sexual function (odds ratio = 5.7; 95% confidence interval 1.6-20.1). CONCLUSION:
      When not in an exacerbation period, the impact of SLE on women's sexual
      functioning is not great and is related to vascular factors.

PMID- 21951617
TI  - Altered ionized magnesium levels in mild-to-moderate Alzheimer's disease.
AB  - Magnesium deficiency is present in several chronic, age-related diseases,
      including cardiovascular, metabolic and neurodegenerative diseases. Alzheimer's
      disease (AD) is the most common cause of dementia. The aim of the present study
      was to study magnesium homeostasis in patients with mild to moderate AD. One
      hundred and one elderly (>=65 years) patients were consecutively recruited (mean
      age: 73.4+/-0.8 years; M/F: 42/59). In all patients, a comprehensive geriatric
      assessment was performed including cognitive and functional status. Admission
      criteria for the AD group (diagnosed according to the DSM-IV and the NINCDS-ADRDA
      criteria) included: mild to moderate cognitive impairment (MMSE score: 11-24/30,
      corrected for age and education). Blood samples were analyzed for serum total
      magnesium (Mg-tot) and serum ionized magnesium (Mg-ion). AD patients had
      significantly lower MMSE scores (20.5+/-0.7 vs 27.9+/-0.2; p<0.001), and for the
      physical function tests. Mg-ion was significantly lower in the AD group as
      compared to age-matched control adults without AD (0.50+/-0.01 mmol/L vs 0.53+/
      0.01 mmol/L; p<0.01). No significant differences were found in Mg-tot between the
      two groups (1.91+/-0.03 mEq/L vs 1.95+/-0.03 mEq/L; p=NS). For all subjects, Mg
      ion levels were significantly and directly related only to cognitive function (Mg
      ion/MMSE r=0.24 p<0.05), while no significant correlations were found in this
      group of patients between magnesium and ADL or IADL. Our results show the
      presence of subclinical alterations in Mg-ion in patients with mild to moderate
      AD.

PMID- 21951618
TI  - Effects of Schisandra chinensis extract on the contractility of corpus cavernosal
      smooth muscle (CSM) and Ca2+ homeostasis in CSM cells.
AB  - What's known on the subject? And what does the study add? Schisandra chinensis
      extract (SCE) has been known to have relaxative effects on penile smooth muscle.
      A recent study showed that SCE could enhance slidenafil citrate-induced
      relaxation of penile corpus cavernosum. The current study investigated the
      mechanism of action of SCE and its constituents on corporal smooth muscle cells.
      And this study shows that SCE induced relaxation of CSM primarily through an
      endothelium independent pathway and the relaxation effects of SCE on corporal
      smooth muscle are, in part, due to the activation of K(+) channels and inhibition
      of TRPC6 channels, resulting in decreased [Ca(2+)]. OBJECTIVE: * To evaluate the
      relaxant effects of Schisandra chinensis extract (SCE) on corporal tissue in the
      penis and to investigate the mechanism of action of SCE and its constituents on
      corporal smooth muscle (CSM) cells. MATERIALS AND METHODS: * The fruit of SC was
      collected and extracted with ethanol. Six SC lignans (schisandrol A, schisandrol
      B, schisandrin A, schisandrin B, gomisin N, and schisandrin C) were isolated and
      purified, and the chemical structures were confirmed by (1)H-nuclear magnetic
      resonance (NMR) and (13)C-NMR data. * Isolated rabbit CSM strips were mounted in
      an organ-bath system, and the effects of SCE were evaluated. * To estimate the
      intracellular Ca(2+) level ([Ca(2+)](i)), we used a Fura-2 fluorescent technique,
      and a conventional whole-cell patch-clamp technique was used to measure the
      calcium-sensitive K(+) channels (K(Ca)), inward rectifier K(+) channels (K(IR)),
      and canonical transient receptor potential cation channel 6 (TRPC6) currents.
      RESULTS: * SCE induced concentration-dependent relaxation in contracted CSM
      tissue, and the removal of the endothelium did not significantly affect their
      relaxation potencies. * In CSM cells, extracellular application of SCE
      significantly increased whole-cell K(Ca) currents (117.4%) and K(IR) currents
      (110.0%). These effects were completely abolished by charybdotoxin or BaCl(2). *
      In contrast, carbachol-induced TRPC6 channel activity was significantly inhibited
      (87.3%) by SCE in green fluorescent protein-TRPC6 pcDNA transfected HEK 293
      cells. [Ca(2+)](i) measurements showed that SCE effectively reduced basal
      [Ca(2+)](i) in both cell lines (CSM cells and A7r5 cells) and the [Arg8]
      vasopressin (AVP)-induced [Ca(2+)](i) increase in A7r5 cells. * Among the six SC
      lignans, schisandrin A and schisandrin B most effectively attenuated the AVP
      induced [Ca(2+)](i) increase. CONCLUSIONS: * SCE induced relaxation of CSM that
      occurred primarily via an endothelium-independent pathway. * The relaxation
      effects of SCE on CSM were, in part, due to the activation of K(+) channels and
      inhibition of TRPC6 channels, resulting in decreased [Ca(2+)](i).

PMID- 21951620
TI  - Detailed tracking of body and leg movements of a freely walking female cricket
      during phonotaxis.
AB  - We describe a semi-automated tracking system for insect motion based on
      commercially available high-speed video cameras and freely available software. We
      use it to collect detailed three-dimensional kinematic information from female
      crickets performing free walking phonotaxis towards a calling song stimulus. We
      mark the insect's joints with small dots of paint and record the movements from
      underneath with a pair of cameras following the insect as it walks on the
      transparent floor of an arena. Tracking is done offline, utilizing a kinematic
      model to constrain the processing. We can obtain the positions and angles of all
      joints of all legs and six additional body joints, synchronised with stance-swing
      transitions and the sound pattern, at a 300 Hz frame rate. This data will be used
      in the further development of models of neural control of phonotaxis.

PMID- 21951619
TI  - Chronic instability of the anterior tibiofibular syndesmosis of the ankle.
      Arthroscopic findings and results of anatomical reconstruction.
AB  - BACKGROUND: The arthroscopic findings in patients with chronic anterior
      syndesmotic instability that need reconstructive surgery have never been
      described extensively. METHODS: In 12 patients the clinical suspicion of chronic
      instability of the syndesmosis was confirmed during arthroscopy of the ankle. All
      findings during the arthroscopy were scored. Anatomical reconstruction of the
      anterior tibiofibular syndesmosis was performed in all patients. The AOFAS score
      was assessed to evaluate the result of the reconstruction. At an average of 43
      months after the reconstruction all patients were seen for follow-up. RESULTS:
      The syndesmosis being easily accessible for the 3 mm transverse end of probe
      which could be rotated around its longitudinal axis in all cases during
      arthroscopy of the ankle joint, confirmed the diagnosis. Cartilage damage was
      seen in 8 ankles, of which in 7 patients the damage was situated at the medial
      side of the ankle joint. The intraarticular part of anterior tibiofibular
      ligament was visibly damaged in 5 patients. Synovitis was seen in all but one
      ankle joint. After surgical reconstruction the AOFAS score improved from an
      average of 72 pre-operatively to 92 post-operatively. CONCLUSIONS: To confirm the
      clinical suspicion, the final diagnosis of chronic instability of the anterior
      syndesmosis can be made during arthroscopy of the ankle. Cartilage damage to the
      medial side of the tibiotalar joint is often seen and might be the result of
      syndesmotic instability. Good results are achieved by anatomic reconstruction of
      the anterior syndesmosis, and all patients in this study would undergo the
      surgery again if necessary.

PMID- 21951621
TI  - Adhesion molecule periplakin is involved in cellular movement and attachment in
      pharyngeal squamous cancer cells.
AB  - BACKGROUND: We previously reported that periplakin (PPL) is downregulated in
      human esophageal cancer tissues compared to the adjacent non-cancer epithelium.
      Thus PPL could be a useful marker for detection of early esophageal cancer and
      evaluation of tumor progression, but largely remains unknown in this field. To
      investigate PPL involvement in carcinogenesis, tumor progression, cellular
      movement or attachment activity, siRNAs against PPL were transfected into
      pharyngeal squamous cancer cell lines and their effects on cellular behaviours
      were examined. RESULTS: PPL knockdown appeared to decrease tumor cell growth
      together with G2/M phase accumulation in cells attached to a culture dish.
      However, the extent of cell growth suppression, evaluated by the number of cells
      attached to the culture dish, was too distinctive to be explained only by cell
      cycle delay. Importantly, PPL knockdown suppressed cellular movement and
      attachment to the culture dish accompanied by decreased pAktSer473
      phosphorylation. Additionally, LY294002, a PI3K inhibitor that dephosphorylates
      pAktSer473, significantly suppressed D562 cell migration. Thus PPL potentially
      engages in cellular movement al least partly via the PI3K/Akt axis. CONCLUSIONS:
      PPL knockdown is related to reduced cellular movement and attachment activity in
      association with PI3K/Akt axis suppression, rather than malignant progression in
      pharyngeal cancer cells.

PMID- 21951622
TI  - First case of Chlamydia trachomatis L2b proctitis in a woman.
AB  - Since 2003, outbreaks of lymphogranuloma venereum (LGV) have been reported in
      European countries, North America, and Australia. Current LGV cases have been
      caused by Chlamydia trachomatis serovar L2. This sexually transmitted infection
      is predominantly found among men who have sex with men, specifically men who are
      seropositive for human immunodeficiency virus and have clinical signs of
      proctitis. The current outbreak has been almost exclusively attributed to a new
      variant, designated L2b. Although urogenital cases of LGV have been described in
      the heterosexual population, we report the first case of C. trachomatis L2b
      proctitis in a woman.

PMID- 21951623
TI  - Efficacy of sorafenib, a multi-tyrosine kinase inhibitor, in an adenoid cystic
      carcinoma metastatic to the lung: case report and review of literature.
AB  - INTRODUCTION: Treatment for squamous cell carcinoma of the head and neck has
      significantly improved with the addition of cetuximab, a monoclonal antibody
      against the epidermal growth factor receptor, to conventional cytotoxic agents.
      The most significant aspect of this treatment approach is the proof that head and
      neck cancers are suitable for targeted therapies as has been shown in other
      malignancies. Unfortunately, there are other rare histologic types of head and
      neck cancer such as adenocarcinoma and adenoid cystic carcinoma. The latter has
      traditionally been considered to be chemotherapy resistant and surgical resection
      with or without adjuvant radiation therapy has been the rule as far as treatment
      is concerned. The course of adenoid cystic carcinoma ranges from indolent to
      aggressive; however, most patients succumb to the disease as a result of distant
      metastases. This clinical scenario poses a challenge to oncologists. Several
      conventional chemotherapy regimens and novel targeted agents have been tried in
      this rare histologic subtype without success. CASE PRESENTATION: In this case
      report, we present a 59-year-old Caucasian female with refractory adenoid cystic
      carcinoma of the maxilla metastatic to the lung that responded to sorafenib, a
      novel multi-tyrosine kinase inhibitor, which targets angiogenesis, Raf kinase
      pathway, platelet-derived growth factor Ret, and c-Kit. CONCLUSION: This case
      illustrates the possibility that this chemoresistant tumor may need the
      inhibition or blocking of several oncogenic pathways. Certainly, it is imperative
      that more studies are done in this special population trying to identify
      tumorigenesis mechanisms that may be upregulated in this malignancy and could be
      potential targets for therapeutic development.

PMID- 21951624
TI  - Liver involvement during influenza infection: perspective on the 2009 influenza
      pandemic.
AB  - Elevation of liver transaminase levels is a frequent observation during systemic
      infections. The aim of our study was to investigate liver damage during pandemic
      2009 influenza A/H1N1 infection in comparison with seasonal influenza. Serum
      levels of aspartate aminotransferase, alanine aminotransferase, and gamma
      glutamyl transpeptidase (GGT) were significantly higher in patients with pandemic
      influenza compared to seasonal influenza, which was strongly correlated with
      hypoxia. Moreover, a positive correlation between C-reactive protein and serum
      GGT, alkaline phosphatase, and lactate dehydrogenase was noticed. Our findings
      support the hypothesis that the pandemic 2009 influenza A/H1N1 is an illness with
      a significant immune response to infection leading to hepatocellular injury.

PMID- 21951625
TI  - Islands in the ice: detecting past vegetation on Greenlandic nunataks using
      historical records and sedimentary ancient DNA meta-barcoding.
AB  - Nunataks are isolated bedrocks protruding through ice sheets. They vary in age,
      but represent island environments in 'oceans' of ice through which organism
      dispersals and replacements can be studied over time. The J.A.D. Jensen's
      Nunataks at the southern Greenland ice sheet are the most isolated nunataks on
      the northern hemisphere - some 30 km from the nearest biological source. They
      constitute around 2 km(2) of ice-free land that was established in the early
      Holocene. We have investigated the changes in plant composition at these nunataks
      using both the results of surveys of the flora over the last 130 years and
      through reconstruction of the vegetation from the end of the Holocene Thermal
      Maximum (5528 +/- 75 cal year BP) using meta-barcoding of plant DNA recovered
      from the nunatak sediments (sedaDNA). Our results show that several of the plant
      species detected with sedaDNA are described from earlier vegetation surveys on
      the nunataks (in 1878, 1967 and 2009). In 1967, a much higher biodiversity was
      detected than from any other of the studied periods. While this may be related to
      differences in sampling efforts for the oldest period, it is not the case when
      comparing the 1967 and 2009 levels where the botanical survey was exhaustive. As
      no animals and humans are found on the nunataks, this change in diversity over a
      period of just 42 years must relate to environmental changes probably being
      climate-driven. This suggests that even the flora of fairly small and isolated
      ice-free areas reacts quickly to a changing climate.

PMID- 21951626
TI  - A subtle interplay between three Pex11 proteins shapes de novo formation and
      fission of peroxisomes.
AB  - The organization of eukaryotic cells into membrane-bound compartments must be
      faithfully sustained for survival of the cell. A subtle equilibrium exists
      between the degradation and the proliferation of organelles. Commonly,
      proliferation is initiated by a membrane remodeling process. Here, we dissect the
      function of proteins driving organelle proliferation in the particular case of
      peroxisomes. These organelles are formed either through a growth and division
      process from existing peroxisomes or de novo from the endoplasmic reticulum (ER).
      Among the proteins involved in the biogenesis of peroxisomes, peroxins, members
      of the Pex11 protein family participate in peroxisomal membrane alterations. In
      the yeast Saccharomyces cerevisiae, the Pex11 family consists of three proteins,
      Pex11p, Pex25p and Pex27p. Here we demonstrate that yeast mutants lacking
      peroxisomes require the presence of Pex25p to regenerate this organelle de novo.
      We also provide evidence showing that Pex27p inhibits peroxisomal function and
      illustrate that Pex25p initiates elongation of the peroxisomal membrane. Our data
      establish that although structurally conserved each of the three Pex11 protein
      family members plays a distinct role. While ScPex11p promotes the proliferation
      of peroxisomes already present in the cell, ScPex25p initiates remodeling at the
      peroxisomal membrane and ScPex27p acts to counter this activity. In addition, we
      reveal that ScPex25p acts in concert with Pex3p in the initiation of de novo
      peroxisome biogenesis from the ER.

PMID- 21951627
TI  - Coronary beta2-adrenoreceptors mediate endothelium-dependent vasoreactivity in
      humans: novel insights from an in vivo intravascular ultrasound study.
AB  - AIMS: The interaction between coronary beta(2)-adrenoreceptors and segmental
      plaque burden is complex and poorly understood in humans. We aimed to validate
      intracoronary (IC) salbutamol as a novel endothelium-dependent vasodilator
      utilizing intravascular ultrasound (IVUS), and thus assess relationships between
      coronary beta(2)-adrenoreceptors, regional plaque burden and segmental
      endothelial function. METHODS AND RESULTS: In 29 patients with near-normal
      coronary angiograms, IVUS-upon-Doppler Flowire imaging protocols were performed.
      Protocol 1: incremental IC salbutamol (0.15, 0.30, 0.60 MUg/min) infusions (15
      patients, 103 segments); protocol 2: salbutamol (0.30 MUg/min) infusion before
      and after IC administration of N(G)-monomethyl-L-arginine (L-NMMA) (10 patients,
      82 segments). Vehicle infusions (IC dextrose) were performed in 4 patients (21
      segments). Macrovascular response [% change segmental lumen volume (DeltaSLV)]
      and plaque burden [per cent atheroma volume (PAV)] were studied in 5-mm coronary
      segments. Microvascular response [per cent change in coronary blood flow
      (DeltaCBF)] was calculated following each infusion. Intracoronary salbutamol
      demonstrated significant dose-response DeltaSLV and DeltaCBF from baseline,
      respectively (0.15 MUg/min: 3.5 +/- 1.3%, 28 +/- 14%, P = 0.04, P = NS; 0.30
      MUg/min: 5.5 +/- 1.4%, 54 +/- 17%, P = 0.001, P < 0.0001; 0.60 MUg/min: 4.8 +/-
      1.6%, 66 +/- 15%, P = 0.02, P < 0.0001), with DeltaSLV responses further
      exemplified in low vs. high plaque burden groups. Salbutamol vasomotor responses
      were suppressed by l-NMMA, supporting nitric oxide-dependent mechanisms. Vehicle
      infusions resulted in no significant DeltaSLV or DeltaCBF. Multivariate analysis
      including conventional cardiovascular risk factors, PAV, segmental remodelling
      and plaque eccentricity indices identified PAV as the only significant predictor
      of a DeltaSLV to IC salbutamol (coefficient -0.18, 95% CI -0.32 to -0.044, P =
      0.015). Conclusions Intracoronary salbutamol is a novel endothelium-dependent
      epicardial and microvascular coronary vasodilator. Intravascular ultrasound
      derived regional plaque burden is a major determinant of segmental coronary
      endothelial function.

PMID- 21951629
TI  - Biventricular pacing: current trends and future strategies.
AB  - The role of biventricular pacing is expanding beyond the New York Heart
      Association classes III and IV heart failure (HF) patient to include less
      symptomatic patients, earlier in the course of their disease process. This
      multisite pacing strategy has substantially altered the natural course of
      ventricular failure, exerting its physiological impact through favourable cardiac
      remodelling and improving the ejection fraction. This has in turn resulted in
      long-term clinical benefits such as improved quality of life and functional
      capacity with a concomitant reduction in hospitalization for HF and overall
      mortality. Despite the successes of cardiac resynchronization therapy (CRT) and
      the recent expansion of its role in the treatment of HF patients, there remain
      some inherent limitations to the technology and its delivery. A significant
      minority of patients continue to remain non-responsive to this pacing strategy.
      This review will highlight biventricular pacing in its present form, will
      elaborate on strategies to enhance response to CRT, and outline future trends and
      synergies towards maximizing the potential benefit of this therapeutic modality.

PMID- 21951630
TI  - SYNTAX score and Clinical SYNTAX score as predictors of very long-term clinical
      outcomes in patients undergoing percutaneous coronary interventions: a substudy
      of SIRolimus-eluting stent compared with pacliTAXel-eluting stent for coronary
      revascularization (SIRTAX) trial.
AB  - AIMS: To investigate the ability of SYNTAX score and Clinical SYNTAX score (CSS)
      to predict very long-term outcomes in an all-comers population receiving drug
      eluting stents. METHODS AND RESULTS: The SYNTAX score was retrospectively
      calculated in 848 patients enrolled in the SIRolimus-eluting stent compared with
      pacliTAXel-Eluting Stent for coronary revascularization (SIRTAX) trial. The CSS
      was calculated using age, and baseline left ventricular ejection fraction and
      creatinine clearance. A stratified post hoc comparison was performed for all
      cause mortality, cardiac death, myocardial infarction (MI), ischaemia-driven
      target lesion revascularization (TLR), definite stent thrombosis, and major
      adverse cardiac events (MACE) at 1- and 5-year follow-up. Tertiles for SYNTAX
      score and CSS were defined as SS(LOW) <= 7, 7< SS(MID) <= 14, SS(HIGH) >14 and
      CSS(LOW) <= 8.0, 8.0 <CSS(MID) <= 17.0 and CSS(HIGH) >17.0, respectively. Major
      adverse cardiac events rates were significantly higher in SS(HIGH) compared with
      SS(LOW) at 1- and 5-year follow-up, which was also seen at 5 years for all-cause
      mortality, cardiac death, MI, and TLR. Stratifying outcomes across CSS tertiles
      confirmed and augmented these results. Within CSS(HIGH), 5-year MACE increased
      with use of paclitaxel- compared with sirolimus-eluting stents (34.7 vs. 21.3%, P
      = 0.008). SYNTAX score and CSS were independent predictors of 5-year MACE; CSS
      was an independent predictor for 5-year mortality. Areas-under-the-curve for
      SYNTAX score and CSS for 5-year MACE were 0.61 (0.56-0.65) and 0.62 (0.57-0.67),
      for 5-year all-cause mortality 0.58 (0.51-0.65) and 0.66 (0.59-0.73) and for 5
      year cardiac death 0.63 (0.54-0.72) and 0.72 (0.63-0.81), respectively.
      CONCLUSION: SYNTAX score and to a greater extent CSS were able to stratify risk
      for very long-term adverse clinical outcomes in an all-comers population
      receiving drug-eluting stents. Predictive accuracy for 5-year all-cause mortality
      was improved using CSS. TRIAL REGISTRATION NUMBER: NCT00297661.

PMID- 21951628
TI  - Therapeutic perspectives in hypertension: novel means for renin-angiotensin
      aldosterone system modulation and emerging device-based approaches.
AB  - The conventional antihypertensive therapies including renin-angiotensin
      aldosterone system antagonists (converting enzyme inhibitors, receptor blockers,
      renin inhibitors, and mineralocorticoid receptor blockers), diuretics, beta
      blockers, and calcium channel blockers are variably successful in achieving the
      challenging target blood pressure values in hypertensive patients. Difficult to
      treat hypertension is still a commonly observed problem world-wide. A number of
      drugs are considered to be used as novel therapies for hypertension. Renalase
      supplementation, vasopeptidase inhibitors, endothelin antagonists, and especially
      aldosterone antagonists (aldosterone synthase inhibitors and novel selective
      mineralocorticoid receptor blockers) are considered an option in resistant
      hypertension. In addition, the aldosterone antagonists as well as (pro)renin
      receptor blockers or AT(2) receptor agonists might attenuate end-organ damage.
      This array of medications has now been complemented by a number of new approaches
      of non-pharmacological strategies including vaccination, genomic interference,
      controlled breathing, baroreflex activation, and probably most successfully renal
      denervation techniques. However, the progress on innovative therapies seems to be
      slow and the problem of resistant hypertension and proper blood pressure control
      appears to be still persisting. Therefore the regimens of currently available
      drugs are being fine-tuned, resulting in the establishment of several novel fixed
      dose combinations including triple combinations with the aim to facilitate proper
      blood pressure control. It remains an exciting question which approach will
      confer the best blood pressure control and risk reduction in this tricky disease.

PMID- 21951631
TI  - Bottlenecks drive temporal and spatial genetic changes in alpine caddisfly
      metapopulations.
AB  - BACKGROUND: Extinction and re-colonisation of local populations is common in
      ephemeral habitats such as temporary streams. In most cases, such population
      turnover leads to reduced genetic diversity within populations and increased
      genetic differentiation among populations due to stochastic founder events,
      genetic drift, and bottlenecks associated with re-colonisation. Here, we examined
      the spatio-temporal genetic structure of 8 alpine caddisfly populations
      inhabiting permanent and temporary streams from four valleys in two regions of
      the Swiss Alps in years before and after a major stream drying event, the
      European heat wave in summer 2003. RESULTS: We found that population turnover
      after 2003 led to a loss of allelic richness and gene diversity but not to
      significant changes in observed heterozygosity. Within all valleys, permanent and
      temporary streams in any given year were not differentiated, suggesting
      considerable gene flow and admixture between streams with differing hydroperiods.
      Large changes in allele frequencies after 2003 resulted in a substantial increase
      in genetic differentiation among valleys within one to two years (1-2
      generations) driven primarily by drift and immigration. Signatures of genetic
      bottlenecks were detected in all 8 populations after 2003 using the M-ratio
      method, but in no populations when using a heterozygosity excess method,
      indicating differential sensitivity of bottleneck detection methods. CONCLUSIONS:
      We conclude that genetic differentiation among A. uncatus populations changed
      markedly both temporally and spatially in response to the extreme climate event
      in 2003. Our results highlight the magnitude of temporal population genetic
      changes in response to extreme events. More specifically, our results show that
      extreme events can cause rapid genetic divergence in metapopulations. Further
      studies are needed to determine if recovery from this perturbation through
      gradual mixing of diverged populations by migration and gene flow leads to the
      pre-climate event state, or whether the observed changes represent a new genetic
      equilibrium.

PMID- 21951633
TI  - Morphology and phylogeny of a new urostylid ciliate, Monocoronella carnea n. g.,
      n. sp. (Ciliophora, Hypotricha) from Daya Bay, Southern China.
AB  - The morphology, infraciliature and small subunit ribosomal RNA gene-based
      phylogeny of an urostylid ciliate, Monocoronella carnea n. g., n. sp., found in
      coastal areas off Daya Bay, Southern China, were investigated. The new genus
      Monocoronella n. g. is recognized by the following features: having conspicuous
      frontal cirri forming a long and single corona; buccal and frontoterminal cirri
      present; single marginal row on each side; adoral zone, midventral complex and
      transverse cirri in Pseudokeronopsis mode. The type species M. carnea n. sp. is
      diagnosed by the combination of marine habitat and brown-reddish color of the
      cortical granules. Phylogenetic analyses for the new taxon indicate that
      Monocoronella n. g. is most closely related to Bergeriella, and is located within
      the core Urostylida clade. A misidentification in previous literature was
      recognized and a new species, Monocoronella dragescoi n. sp. [Basionym:
      Holosticha (Keronopsis) monilata (Kahl 1928) sensu Dragesco (1970) et sensu
      Dragesco and Dragesco-Kerneis (1986), non sensu Kahl (1928)], was suggested.

PMID- 21951632
TI  - Activation and role of the medial prefrontal cortex (mPFC) in extinction of
      ethanol-induced associative learning in mice.
AB  - Although the medial prefrontal cortex (mPFC) has been shown to be integrally
      involved in extinction of a number of associative behaviors, its role in
      extinction of alcohol (ethanol)-induced associative learning has received little
      attention. Previous reports have provided evidence supporting a role for the mPFC
      in acquisition and extinction of amphetamine-induced conditioned place preference
      (CPP) in rats, however, it remains unknown if this region is necessary for
      extinction of ethanol (EtOH)-induced associative learning in mice. Using
      immunohistochemical analysis of phosphorylated and unphosphorylated cAMP response
      element-binding protein (CREB), the current set of experiments first showed that
      the prelimbic (PL) and infralimbic (IL) subregions of the mPFC exhibited dynamic
      responses in phosphorylation of CREB to a Pavlovian-conditioned, EtOH-paired cue.
      Interestingly, CREB phosphorylation within these regions was sensitive to
      manipulations of the EtOH-cue contingency-that is, the cue-induced increase of
      pCREB in both the PL and IL was absent following extinction. In order to confirm
      a functional role of the mPFC in regulating the extinction process, we then
      showed that electrolytic lesions of the mPFC following acquisition blocked
      subsequent extinction of EtOH-CPP. Together, these experiments indicate a role
      for the PL and IL subregions of the mPFC in processing changes of the EtOH-cue
      contingency, as well as in regulating extinction of EtOH-induced associative
      learning in mice.

PMID- 21951635
TI  - The ethical complexities of online organ solicitation via donor-patient websites:
      avoiding the "beauty contest".
AB  - The proliferation of the Internet has spurred the creation of websites dedicated
      to facilitating living directed organ donations. We argue that such sites
      potentially devolve into "beauty contests" where patients in need are evaluated
      on the basis of their personal appearance and biography-variables which should
      have no relevance to organ allocation. Altruism should be the guiding motivation
      for all donations, and when it does, there is no place for a beauty contest. The
      power of the Internet is optimally used when it facilitates Good Samaritan
      donations-donations to any stranger, rather than handpicked ones. Social
      networking sites which aim to match potential donors and patients should mask
      personal identifying information, allowing the ethical principles of altruism and
      justice to guide organ allocation.

PMID- 21951634
TI  - A novel diagnostic platform based on multiplex ligase detection-PCR and
      microarray for simultaneous detection of swine viruses.
AB  - Simultaneous detection and identification of multiple pathogens is required in
      many diagnostic fields. In this study a novel method based on a multiplex ligase
      detection (LD)-polymerase chain reaction (PCR) and microarray (MLPM) is described
      to detect simultaneously several swine viruses involved in reproductive and/or
      respiratory problems. The multiplex diagnostic system was validated using
      standard plasmids, and clinical samples. Using this strategy as few as 10 copies
      of target plasmids were detected successfully. Each probe pair yielded specific
      positive signal only in its target site. In addition, when six target plasmids
      were present simultaneously sufficient robust signals were generated in their
      corresponding sites of six plasmid templates and no obvious signals were detected
      in non-target sites. Compared to real-time PCR, the MLPM showed specificities and
      sensitivities of 95.7-100% and 100% for 47 clinical samples tested, respectively.
      The results demonstrate that this novel assay is a specific, sensitive, and
      multiplex diagnostic method for detection of multiple pathogens and can also be
      adapted easily for diagnostic purposes.

PMID- 21951636
TI  - Determination of fluid status in haemodialysis patients with whole body and calf
      bioimpedance techniques.
AB  - AIM: The aim of this study was to demonstrate the ability of widely used
      bioimpedance techniques to assess dry weight (DW) and to predict a state of
      normal hydration in haemodialysis patients whose post-dialysis weight had been
      gradually reduced from baseline in successive treatments over time. METHODS: Calf
      bioimpedance spectroscopy (cBIS) was employed to determine DW (DW(cBIS) ) as
      defined by flattening of an intradialytic continuously measured resistance curve
      and by normalized resistivity (nRho) being in the gender-specific normal range.
      The wECV/TBW ratio was determined by 'classical' wrist-to-ankle whole body
      bioimpedance spectroscopy (wBIS); in addition, a novel whole body model (WBM)
      based on wBIS was used to predict normal hydration weight (NHW(WBM) ). RESULTS:
      Twenty-one haemodialysis patients were studied; 11 +/- 6 measurements were
      performed per patient. Nine patients reached DW(cBIS) (DW(cBIS) group), while 12
      patients remained fluid-overloaded (non-DW(cBIS) group). Change in wECV as
      measured by wBIS accounted for 46 +/- 23% in DW(cBIS) group, which was higher
      than in non-DW(cBIS) group (33 +/- 48%, P < 0.05) of actual weight loss at the
      end of study. In both groups the wECV/TBW ratio did not change significantly
      between baseline and study end. Mean predicted NHW(WBM) at baseline was 3.55 +/-
      1.6 kg higher than DW(cBIS) . The difference in DW(cBIS) and NHW(WBM) was 1.97 +/
      1.0 kg at study end. CONCLUSION: WBM could be useful to predict a target range
      of normal hydration weight particularly for patients with substantial fluid
      overload. The cBIS provides an accurate reference for the estimation of DW so
      that combined use of cBIS and WBM is promising and warrants further studies.

PMID- 21951637
TI  - Tertiary interactions between helices h13 and h44 in 16S RNA contribute to the
      fidelity of translation.
AB  - The A-minor interaction, formed between single-stranded adenosines and the minor
      groove of a receptor helix, is among the most common motifs found in rRNA. Among
      the A-minors found in 16S rRNA are a set of interactions between adenosines at
      positions 1433, 1434 and 1468 in helix 44 (h44) and their receptors in the
      nucleotide 320-340 region of helix 13 (h13). These interactions have been
      implicated in the maintenance of translational accuracy, because base
      substitutions at the adjacent C1469 increase miscoding errors. We have tested
      their functional significance through mutagenesis of h13 and h44. Mutations at
      the h44 A residues, or the A-minor receptors in h13, increase a variety of
      translational errors and a subset of the mutants show decreased association
      between 30S and 50S ribosomal subunits. These results are consistent with the
      involvement of h13-h44 interactions in the alignment and packing of these helices
      in the 30S subunit and the importance of this helical alignment for tRNA
      selection and subunit-subunit interaction.

PMID- 21951638
TI  - Pandemic influenza A (H1N1) virus in households with young children.
AB  - BACKGROUND: Influenza viruses may cause a severe infection in infants and young
      children. The transmission patterns of pandemic 2009 influenza A (H1N1) within
      households with young children are poorly characterized. METHODS: Household
      members of six children younger than 1.5 years with documented 2009 influenza A
      (H1N1) infection were studied by daily symptom diaries and serial parent
      collected nasal swab samples for detection of influenza A by reverse
      transcription polymerase chain reaction (RT-PCR) assay. RESULTS: Laboratory
      confirmed, symptomatic influenza was documented in 11 of 15 household contacts of
      young children with pandemic influenza (73%; 95% CI, 48-99). In five contact
      cases symptoms started earlier, in three cases on the same day, and in three
      cases after the onset of symptoms in the youngest child. The first case with
      influenza A (H1N1) within the household was an elder sibling in two households,
      father in two households, the youngest child in one household, and the youngest
      child at the same time with a sibling in one household. The median copy number of
      influenza virus was higher in children than in adults (4.2 * 10(7) versus 4.9 *
      10(4), P = 0.02). CONCLUSIONS: This study demonstrates the feasibility of nasal
      swab sampling by parents in investigation of household transmission of influenza.
      The results support influenza vaccination of all household contacts of young
      children.

PMID- 21951639
TI  - DNA barcoding of endangered Indian Paphiopedilum species.
AB  - The indiscriminate collections of Paphiopedilum species from the wild for their
      exotic ornamental flowers have rendered these plants endangered. Although the
      trade of these endangered species from the wild is strictly forbidden, it
      continues unabated in one or other forms that elude the current identification
      methods. DNA barcoding that offers identification of a species even if only a
      small fragment of the organism at any stage of development is available could be
      of great utility in scrutinizing the illegal trade of both endangered plant and
      animal species. Therefore, this study was undertaken to develop DNA barcodes of
      Indian species of Paphiopedilum along with their three natural hybrids using loci
      from both the chloroplast and nuclear genomes. The five loci tested for their
      potential as effective barcodes were RNA polymerase-beta subunit (rpoB), RNA
      polymerase-beta' subunit (rpoC1), Rubisco large subunit (rbcL) and maturase K
      (matK) from the chloroplast genome and nuclear ribosomal internal transcribed
      spacer (nrITS) from the nuclear genome. The intra- and inter-specific divergence
      values and species discrimination rates were calculated by Kimura 2 parameter
      (K2P) method using mega 4.0. The matK with 0.9% average inter-specific divergence
      value yielded 100% species resolution, thus could distinguish all the eight
      species of Paphiopedilum unequivocally. The species identification capability of
      these sequences was further confirmed as each of the matK sequences was found to
      be unique for the species when a blast analysis of these sequences was carried
      out on NCBI. nrITS, although had 4.4% average inter-specific divergence value,
      afforded only 50% species resolution. DNA barcodes of the three hybrids also
      reflected their parentage.

PMID- 21951640
TI  - Conserved cysteine residues in the mammalian lamin A tail are essential for
      cellular responses to ROS generation.
AB  - Pre-lamin A and progerin have been implicated in normal aging, and the
      pathogenesis of age-related degenerative diseases is termed 'laminopathies'.
      Here, we show that mature lamin A has an essential role in cellular fitness and
      that oxidative damage to lamin A is involved in cellular senescence. Primary
      human dermal fibroblasts (HDFs) aged replicatively or by pro-oxidants acquire a
      range of dysmorphic nuclear shapes. We observed that conserved cysteine residues
      in the lamin A tail domain become hyperoxidized in senescent fibroblasts, which
      inhibits the formation of lamin A inter- and intramolecular disulfide bonds. Both
      in the absence of lamin A and in the presence of a lamin A cysteine-to-alanine
      mutant, which eliminates these cysteine residues (522, 588, and 591), mild
      oxidative stress induced nuclear disorganization and led to premature senescence
      as a result of decreased tolerance to ROS stimulators. Human dermal fibroblasts
      lacking lamin A or expressing the lamin A cysteine-to-alanine mutant displayed a
      gene expression profile of ROS-responsive genes characteristic of chronic ROS
      stimulation. Our findings suggest that the conserved C-terminal cysteine residues
      are essential for lamin A function and that loss or oxidative damage to these
      cysteine residues promotes cellular senescence.

PMID- 21951641
TI  - Modelling the effect of temperature, water activity and pH on the growth of
      Serpula lacrymans.
AB  - AIMS: To predict the risk factors for building infestation by Serpula lacrymans,
      which is one of the most destructive fungi causing timber decay in buildings.
      METHODS AND RESULTS: The growth rate was assessed on malt extract agar media at
      temperatures between 1.5 and 45 degrees C, at water activity (a(w)) over the
      range of 0.800-0.993 and at pH ranges from 1.5 to 11.0. The radial growth rate
      (MU) and the lag phase (lambda) were estimated from the radial growth kinetics
      via the plots radius vs time. These parameters were then modelled as a function
      of the environmental factors tested. Models derived from the cardinal model (CM)
      were used to fit the experimental data and allowed an estimation of the optimal
      and limit values for fungal growth. Optimal growth rate occurred at 20 degrees C,
      at high a(w) level (0.993) and at a pH range between 4.0 and 6.0. The strain
      effect on the temperature parameters was further evaluated using 14 strains of S.
      lacrymans. The robustness of the temperature model was validated on data sets
      measured in two different wood-based media (Quercus robur L. and Picea abies).
      CONCLUSIONS: The two-step procedure of exponential model with latency followed by
      the CM with inflection gives reliable predictions for the growth conditions of a
      filamentous fungus in our study. The procedure was validated for the study of
      abiotic factors on the growth rate of S. lacrymans. SIGNIFICANCE AND IMPACT OF
      THE STUDY: This work describes the usefulness of evaluating the effect of physico
      chemical factors on fungal growth in predictive building mycology. Consequently,
      the developed mathematical models for predicting fungal growth on a macroscopic
      scale can be used as a tool for risk assessment of timber decay in buildings.

PMID- 21951643
TI  - Influences of graphene oxide support on the electrochemical performances of
      graphene oxide-MnO2 nanocomposites.
AB  - MnO2 supported on graphene oxide (GO) made from different graphite materials has
      been synthesized and further investigated as electrode materials for
      supercapacitors. The structure and morphology of MnO2-GO nanocomposites are
      characterized by X-ray diffraction, X-ray photoemission spectroscopy, scanning
      electron microscopy, transmission electron microscopy, Raman spectroscopy, and
      Nitrogen adsorption-desorption. As demonstrated, the GO fabricated from
      commercial expanded graphite (denoted as GO(1)) possesses more functional groups
      and larger interplane gap compared to the GO from commercial graphite powder
      (denoted as GO(2)). The surface area and functionalities of GO have significant
      effects on the morphology and electrochemical activity of MnO2, which lead to the
      fact that the loading amount of MnO2 on GO(1) is much higher than that on GO(2).
      Elemental analysis performed via inductively coupled plasma optical emission
      spectroscopy confirmed higher amounts of MnO2 loading on GO(1). As the electrode
      of supercapacitor, MnO2-GO(1) nanocomposites show larger capacitance (307.7 F g
      1) and better electrochemical activity than MnO2-GO(2) possibly due to the high
      loading, good uniformity, and homogeneous distribution of MnO2 on GO(1) support.

PMID- 21951644
TI  - Heat shock protein 90 regulates phosphatidylinositol 3-kinase-related protein
      kinase family proteins together with the RUVBL1/2 and Tel2-containing co-factor
      complex.
AB  - Heat shock protein 90 (Hsp90), a conserved molecular chaperone for a specific set
      of proteins critical for signal transduction including several oncogenic
      proteins, has been recognized as a promising target for anticancer therapy. Hsp90
      inhibition also sensitizes cancer cells to DNA damage. However, the underlying
      mechanisms are not fully understood. Here, we provide evidence that Hsp90 is a
      general regulator of phosphatidylinositol 3-kinase-related protein kinase (PIKK)
      family proteins, central regulators of stress responses including DNA damage.
      Inhibition of Hsp90 causes a reduction of all PIKK and suppresses PIKK-mediated
      signaling. In addition, Hsp90 forms complexes with RUVBL1/2 complex and Tel2
      complex, both of which have been shown to interact with all PIKK and control
      their abundance and functions. These results suggest that Hsp90 can form multiple
      complexes with the RUVBL1/2 complex and Tel2 complex and function in the
      regulation of PIKK, providing additional rationale for the effectiveness of Hsp90
      inhibition for anticancer therapy, including sensitization to DNA damage.

PMID- 21951645
TI  - Erectile function and sexual satisfaction before and after penile prosthesis
      implantation in radical prostatectomy patients: a comparison with patients with
      vasculogenic erectile dysfunction.
AB  - INTRODUCTION: Patients with erectile dysfunction (ED) after radical prostatectomy
      (RP) may benefit from penile prosthesis (PP) implantation after failure of less
      invasive treatments. Aim.  To assess surgical outcomes and satisfaction after PP
      implantation in RP patients and compare the results with those in patients with
      vasculogenic ED (controls). METHODS: A database of 415 consecutive PPs (January
      1996-December 2008) was used to collate data on preimplantation ED treatments,
      surgical complications, satisfaction, and International Index of Erectile
      Function (IIEF) scores before and 3 months after implantation. The results for 90
      post-RP implants (79 primary, 11 secondary) and 131 implants for vasculogenic ED
      were compared. MAIN OUTCOME MEASURES: The main outcome measures of this study are
      intra- and postoperative complications and IIEF domain scores. RESULTS: Mean
      follow-up of RP patients was 37.6 +/- 26.8 months. Mean interval between RP and
      PP implantation was 31.5 +/- 28.7 months. Nearly all primary implants (96.2%)
      were inflatable (3-piece, 70.1%; 2-piece, 24.1%). There was no significant
      difference between groups in terms of rates of infection (1.1%), mechanical
      failure (3.3%), and other surgical complications requiring revision surgery
      (migration, auto-inflation) (4.4%). For primary implants, the mean
      preimplantation IIEF score (all items) was significantly lower in RP patients
      than in controls (14.7 +/- 5.9 vs. 22.6 +/- 10.8, P = 0.003), chiefly because of
      significantly lower scores for erectile function, intercourse satisfaction, and
      orgasmic function. After PP implantation in RP patients, the scores for all
      domains improved, but the total score remained significantly lower than in
      controls (63.1 +/- 7.0 vs. 68.5 +/- 6.9, P = 0.005). The orgasmic function score
      was significantly lower (P < 0.001). Overall satisfaction rate was 86.1% in RP
      patients and 90.7% in controls (P = 0.3). CONCLUSIONS: PP implantation after RP
      is associated with low morbidity and high satisfaction. It improves the scores
      for all IIEF domains and, in particular, erectile function. Fibrosis of the
      retropubic space may require a second incision for reservoir placement or
      implantation of a 2-piece PP.

PMID- 21951646
TI  - Adolescent temperament and parental control in the development of the adolescent
      decision making in a Chilean sample.
AB  - The study analyzes the way in which adolescents' temperamental characteristics
      interact with parental control to shape adolescent decision making development. A
      sample of high-school Chilean adolescents (N = 391) answered a self-report
      questionnaire that included measures of behavioral autonomy (the extent to which
      adolescents make decisions in personal and prudential domains), parental
      behavioral and psychological control, and temperamental characteristics. A path
      analysis model indicated that adolescents' anger-frustration had a direct
      association with decision-making in the personal and prudential domains;
      fearfulness had an inverse association with adolescent decision-making, but only
      in the prudential domain. Perceived psychological control was associated with
      adolescents' reduced decision-making autonomy in the personal domain, while
      perceived behavioral control was associated with less adolescent autonomy in both
      personal and prudential domains. Additionally, a moderation effect was found such
      that the association of parental behavioral control on decision-making in the
      prudential domain was dependent on the adolescent fearfulness level.

PMID- 21951647
TI  - Cytoreductive nephrectomy in the elderly: a population-based cohort from the USA.
AB  - Study Type - Therapy (cohort) Level of Evidence 2b What's known on the subject?
      and What does the study add? While cytoreductive nephrectomy is associated with a
      survival benefit in the context of metastatic renal cell carcinoma, the rates of
      morbidity and perioperative mortality remain non-negligible. For example,
      perioperative mortality may be as high as 21% in elderly patients. The study
      shows that perioperative death amongst the elderly was substantially lower than
      what was previously reported from a single institutional report. Nonetheless,
      postoperative adverse outcomes were non-negligible in elderly patients relative
      to their younger counterparts. In consequence, these rates should be discussed at
      informed consent and a rigorous patient selection remains essential. OBJECTIVE: *
      To examine the rate of perioperative mortality (PM), and other adverse outcomes
      in 'elderly' patients treated with cytoreductive nephrectomy (CNT). MATERIAL AND
      METHODS: * Patients who underwent CNT for metastatic renal cell carcinoma were
      abstracted from the Nationwide Inpatient Sample (1998-2007). 'Elderly' was
      defined as >= 75 years, according to previous definition. * Endpoints consisted
      of PM, intraoperative and postoperative complications, blood transfusions and
      length of stay. * We adjusted for the effect of elderly status within five
      separate logistic regression models. Covariates consisted of comorbidity, race,
      gender, year of surgery and hospital region. RESULTS: * Overall, CNT was
      performed in 504 (15.3%) elderly patients and in 2796 (84.7%) 'younger' patients
      (<75 years). * The rate of PM was 4.8% in elderly patients vs 1.9% in the younger
      patients (P < 0.001). Similarly, the rates of blood transfusions (29.8 vs 21.5%),
      postoperative complications (27.8 vs 22.8%), and prolonged length of stay (>= 8
      days) were higher in the elderly (45.0 vs 32.0%; all P < 0.001). * In
      multivariable analyses, elderly patients were 2.2-, 1.5-, and 1.6 fold more
      likely to experience PM, to receive a blood transfusion and to be hospitalized >=
      8 days than the younger patients. CONCLUSIONS: * Although the rate of PM was
      substantially lower than 21%, elderly patients are significantly more likely to
      die after this type of surgery, to receive a transfusion, and to experience a
      prolonged length of stay. * These facts and figures should be discussed at
      informed consent and a rigorous patient selection is essential.

PMID- 21951648
TI  - Novel dimeric beta-helical model of an ice nucleation protein with bridged active
      sites.
AB  - BACKGROUND: Ice nucleation proteins (INPs) allow water to freeze at high subzero
      temperatures. Due to their large size (>120 kDa), membrane association, and
      tendency to aggregate, an experimentally-determined tertiary structure of an INP
      has yet to be reported. How they function at the molecular level therefore
      remains unknown. RESULTS: Here we have predicted a novel beta-helical fold for
      the INP produced by the bacterium Pseudomonas borealis. The protein uses internal
      serine and glutamine ladders for stabilization and is predicted to dimerize via
      the burying of a solvent-exposed tyrosine ladder to make an intimate hydrophobic
      contact along the dimerization interface. The manner in which PbINP dimerizes
      also allows for its multimerization, which could explain the aggregation
      dependence of INP activity. Both sides of the PbINP structure have tandem arrays
      of amino acids that can organize waters into the ice-like clathrate structures
      seen on antifreeze proteins. CONCLUSIONS: Dimerization dramatically increases the
      'ice-active' surface area of the protein by doubling its width, increasing its
      length, and presenting identical ice-forming surfaces on both sides of the
      protein. We suggest that this allows sufficient anchored clathrate waters to
      align on the INP surface to nucleate freezing. As PbINP is highly similar to all
      known bacterial INPs, we predict its fold and mechanism of action will apply to
      these other INPs.

PMID- 21951649
TI  - Dietary Mg2+ regulates the epithelial Mg2+ channel TRPM6 in rat mammary tissue.
AB  - The epithelial Mg(2+) channel TRPM6 is considered a pivotal component in active
      Mg(2+)absorption and re-absorption in the intestine and kidney, but its
      expression and function in other tissues are largely unknown. We have previously
      demonstrated that extracellular Mg(2+) availability modulates TRPM6, but not the
      ubiquitous TRPM7, in cultured mammary epithelial cells; in addition, TRPM6
      protein expression correlated to Mg(2+) influx capacities. Our results closely
      remind the modulation of TRPM6 described by others in murine kidney and colon
      following Mg(2+) dietary restriction. We sought to validate our observations by
      investigating whether TRPM6 modulation by extracellular Mg(2+)also occurs in
      vivo. To this aim, we exploited a model consisting of rats fed either with a
      Mg(2+)-deficient or a Mg(2+)-enriched diet, and studied TRPM6 expression in
      breast and kidney tissues. Immunohistochemical and western blot analyses
      confirmed that rat mammary tissues express TRPM6 protein levels similar to those
      found in the kidney, and that protein expression is modulated by dietary Mg(2+).
      In particular, Mg(2+) restriction upregulated TRPM6 expression, while Mg(2+)
      supplementation resulted in a significant decrease in protein levels. This work
      confirms and extends our previous results on TRPM6 modulation by Mg(2+)
      availability in mammary tissues. Further studies are required to clarify the
      functional significance of these findings, and the role of TRPM6 in tissue
      specific magnesium homeostasis.

PMID- 21951650
TI  - Psychometric evaluation of the Forensic Inpatient Observation Scale (FIOS) in
      youngsters with a judicial measure.
AB  - BACKGROUND: In this article, the psychometric properties of the Forensic
      Inpatient Observation Scale (FIOS) were examined. This instrument was developed
      to observe behavioral functioning of forensic psychiatric patients. Up till now,
      it has only been used among adult forensic psychiatric patients and this is the
      first study in which the FIOS is used with youngsters. METHODS: Data were
      gathered of 133 patients. The FIOS was routinely used to assess the psychiatric
      condition of youngsters at fixed intervals with a three-month time period between
      each measurement. Ward staff working in close contact with the patient conducted
      the assessments. Of these 133 patients, an YSR/ASR questionnaire was available
      for 96 of them and a TRF for 110 of the 133 patients. For the descriptive,
      reliability and validity analyses, SPSS version 16.0 was used. Factor analyses
      were performed by means of Mplus Version 5.2. RESULTS: A series of confirmatory
      and exploratory factor analyses revealed a five-factor structure for the FIOS.
      The five-factor structure consisted of the following scales: self-care, social
      behavior, oppositional behavior, verbal skills and distress. The insight scale of
      the original factor structure could not be replicated in the youth sample.
      Cronbach's alpha's of the five scales ranged from .70 to .85. The self-care,
      verbal skills and oppositional behavior scales of the FIOS showed no relation
      with emotional and behavior problems reported by the patients themselves or their
      teachers. The distress scale of the FIOS did show a relation with the emotional
      problems reported by patients themselves and the social behavior scale with
      behavioral problems as reported by teachers. CONCLUSIONS: The internal
      consistency of the FIOS was sufficient and the factor structure in the present
      sample of youngsters was in general comparable to the original factor structure
      in an adult sample. Its value lies in the focus on behavioral functioning of
      youngsters with judicial measures. What remains to be seen is whether this
      instrument is sensitive enough to register all aspects of behavioral changes,
      whether the interrater reliability is sufficient, and whether it has predictive
      validity to relapse and recidivism.

PMID- 21951651
TI  - Regulation of the MVB pathway by SCAMP3.
AB  - The biogenesis of multivesicular endosomes and the sorting of activated signaling
      receptors into multivesicular endosomes depend on soluble protein complexes
      (ESCRT complexes), which transiently interact with the receptor cargo and the
      endosomal membrane. Previously, it was shown that the transmembrane protein
      secretory carrier membrane protein (SCAMP) 3, which is present on endosomes,
      interacts with ESCRT components. Here, we report that SCAMP3 plays a role in the
      biogenesis of multivesicular endosomes. We find that SCAMP3 plays a role in EGF
      receptor sorting into multivesicular endosomes and in the formation of
      intralumenal vesicles within these endosomes in vitro and thus also controls EGF
      receptor targeting to lysosomes. We also find that SCAMP3 regulates the EGF
      dependent biogenesis of multivesicular endosomes. We conclude that the
      transmembrane protein SCAMP3 has a positive role in sorting into and budding of
      intralumenal vesicles and thereby controls the process of multivesicular endosome
      biogenesis.

PMID- 21951652
TI  - Diagnostic accuracy of venous blood gas electrolytes for identifying diabetic
      ketoacidosis in the emergency department.
AB  - OBJECTIVES: Diagnosing diabetic ketoacidosis (DKA) has traditionally required a
      venous blood gas (VBG) to obtain serum pH and a serum chemistry panel to obtain
      electrolyte values. Because newer blood gas analyzers have the ability to report
      electrolyte values and glucose in addition to pH, this diagnostic process could
      theoretically be condensed. However, neither the diagnostic accuracy of the VBG
      for DKA nor the agreement between the VBG electrolytes and the serum chemistry
      electrolytes, including sodium, chloride, and bicarbonate, has been evaluated in
      the context of acute hyperglycemia. The purpose of this study was to assess the
      accuracy of VBG electrolytes for diagnosing DKA using serum chemistry
      electrolytes measures as the criterion standard and to describe the correlation
      between VBG and serum chemistry electrolytes in a sample of hyperglycemic
      patients seen in the emergency department (ED). METHODS: The authors
      prospectively identified a convenience sample of ED patients with serum blood
      glucose >= 250 mg/dL and examined their paired VBG and serum chemistry
      electrolytes. The diagnosis of DKA was made by using American Diabetes
      Association (ADA) criteria including serum glucose >= 250 mg/dL, serum anion gap
      > 10 mEq/L, bicarbonate <= 18 mEq/L, serum pH <= 7.30, and presence of ketosis.
      Serum chemistry electrolyte values were considered to be the criterion standard.
      Diagnostic test characteristics of VBG electrolytes including sensitivity and
      specificity were compared against this standard. In addition, correlation
      coefficients for individual electrolytes and anion gap between VBG and chemistry
      electrolytes were calculated. RESULTS: Paired VBG and serum chemistry panels were
      available for 342 patients, of whom 46 (13.5%) had DKA. The sensitivity and
      specificity of the VBG electrolytes for diagnosing DKA was 97.8% (95% confidence
      interval [CI] = 88.5% to 99.9%) and 100% (95% CI = 98.8% to 100%), respectively.
      One case of DKA was missed by the VBG. Correlation coefficients between VBG and
      serum chemistry were 0.90, 0.73, 0.94, and 0.81 for sodium, chloride,
      bicarbonate, and anion gap, respectively. CONCLUSIONS: The VBG electrolytes were
      97.8% sensitive and 100% specific for the diagnosis of DKA in hyperglycemic
      patients. These preliminary findings support the use of VBG electrolytes in lieu
      of VBG along with serum chemistry analysis to rule in or rule out DKA.

PMID- 21951654
TI  - Effects of corticosteroids injection in rotator cuff tears.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of intraarticular
      injections of corticosteroids (triamcinolone) in patients with symptomatic
      rotator cuff tears (RCT). DESIGN: Randomized controlled study. SETTING:
      Rehabilitation unit. PATIENTS: Sixty patients with full-thickness RCT were
      enrolled in the study. Patients were randomly divided into three equal groups of
      20 patients. The first group received single intraarticular injection of 40 mg
      triamcinolone, the second group received two injections of 40 mg triamcinolone at
      21-day interval, and the third group received no treatment (control group). All
      patients underwent rehabilitation sessions. Outcome measures were pain, evaluated
      using a visual analog scale, and shoulder functional status, evaluated by
      Constant-Murley score. MEASURES: Outcome measures were pain, evaluated using a
      visual analog scale, and shoulder functional status, evaluated by Constant-Murley
      score. RESULTS: Pain at night score of both groups who received triamcinolone was
      lower than that of Control Group at 1 month (P < 0.05 and P < 0.01 in first and
      second groups, respectively) and at 3 months (P < 0.05 and P < 0.01 in the first
      and second groups, respectively). Similarly, activity pain score of groups
      treated with triamcinolone was lower than that of the control group at 1 month (P
      < 0.001 in both groups) and at 3 months (P < 0.001 in both groups). There was no
      statistically significant difference in pain at night between the first and
      second groups at 1 and at 3 months. There was no statistically significant
      difference among groups at 3 and 6 months in Constant-Murley scores. CONCLUSIONS:
      Our study indicates that intraarticular injection of triamcinolone improves pain
      relief for 3 months in RCT and its action is not prolonged or potentiated by two
      injections of the drug done at 21-day intervals.

PMID- 21951653
TI  - Development of a Pacific oyster (Crassostrea gigas) 31,918-feature microarray:
      identification of reference genes and tissue-enriched expression patterns.
AB  - BACKGROUND: Research using the Pacific oyster Crassostrea gigas as a model
      organism has experienced rapid growth in recent years due to the development of
      high-throughput molecular technologies. As many as 56,268 EST sequences have been
      sequenced to date, representing a genome-wide resource that can be used for
      transcriptomic investigations. RESULTS: In this paper, we developed a Pacific
      oyster microarray containing oligonucleotides representing 31,918 transcribed
      sequences selected from the publicly accessible GigasDatabase. This newly
      designed microarray was used to study the transcriptome of male and female
      gonads, mantle, gills, posterior adductor muscle, visceral ganglia, hemocytes,
      labial palps and digestive gland. Statistical analyses identified genes
      differentially expressed among tissues and clusters of tissue-enriched genes.
      These genes reflect major tissue-specific functions at the molecular level, such
      as tissue formation in the mantle, filtering in the gills and labial palps, and
      reproduction in the gonads. Hierarchical clustering predicted the involvement of
      unannotated genes in specific functional pathways such as the insulin/NPY
      pathway, an important pathway under study in our model species. Microarray data
      also accurately identified reference genes whose mRNA level appeared stable
      across all the analyzed tissues. Adp-ribosylation factor 1 (arf1) appeared to be
      the most robust reference for normalizing gene expression data across different
      tissues and is therefore proposed as a relevant reference gene for further gene
      expression analysis in the Pacific oyster. CONCLUSIONS: This study provides a new
      transcriptomic tool for studies of oyster biology, which will help in the
      annotation of its genome and which identifies candidate reference genes for gene
      expression analysis.

PMID- 21951655
TI  - Houttuynia cordata blocks HSV infection through inhibition of NF-kappaB
      activation.
AB  - Houttuynia cordata Thunb. is a medicinal plant widely used in folk medicine in
      several Asian countries. It has been reported that a water extract of H. cordata
      exhibits activity against herpes simplex virus (HSV) and the virus of severe
      acute respiratory syndrome (SARS), although the mechanisms are not fully
      understood yet. Previous studies have demonstrated absolute requirement of NF
      kappaB activation for efficient replication of HSV-1 and HSV-2 and inhibition of
      NF-kappaB activation has been shown to suppress HSV infection. Here we show that
      a hot water extract of H. cordata (HCWE) inhibits HSV-2 infection through
      inhibition of NF-kappaB activation. The IC(50) was estimated at 50 MUg/ml of
      lyophilized HCWE powder. At 150 and 450 MUg/ml, HCWE blocked infectious HSV-2
      production by more than 3 and 4 logs, respectively. The inhibitory activity was
      concomitant with an inhibition of NF-kappaB activation by HSV-2 infection.
      Although activation of NF-kappaB and Erk MAPK has been implicated for HSV
      replication and growth, HCWE showed no effect on HSV-2-induced Erk activation.
      Furthermore, we show that treatment with quercetin, quercitrin or isoquercitrin,
      major water extractable flavonoids from H. cordata, significantly blocked HSV-2
      infection. These results together demonstrated that H. cordata blocks HSV-2
      infection through inhibition of NF-kappaB activation.

PMID- 21951656
TI  - Effect of point-of-care CD4 cell count tests on retention of patients and rates
      of antiretroviral therapy initiation in primary health clinics: an observational
      cohort study.
AB  - BACKGROUND: Loss to follow-up of HIV-positive patients before initiation of
      antiretroviral therapy can exceed 50% in low-income settings and is a challenge
      to the scale-up of treatment. We implemented point-of-care counting of CD4 cells
      in Mozambique and assessed the effect on loss to follow-up before immunological
      staging and treatment initiation. METHODS: In this observational cohort study,
      data for enrolment into HIV management and initiation of antiretroviral therapy
      were extracted retrospectively from patients' records at four primary health
      clinics providing HIV treatment and point-of-care CD4 services. Loss to follow-up
      and the duration of each preparatory step before treatment initiation were
      measured and compared with baseline data from before the introduction of point-of
      care CD4 testing. FINDINGS: After the introduction of point-of-care CD4 the
      proportion of patients lost to follow-up before completion of CD4 staging dropped
      from 57% (278 of 492) to 21% (92 of 437) (adjusted odds ratio [OR] 0.2, 95% CI
      0.15-0.27). Total loss to follow-up before initiation of antiretroviral treatment
      fell from 64% (314 of 492) to 33% (142 of 437) (OR 0.27, 95% CI 0.21-0.36) and
      the proportion of enrolled patients initiating antiretroviral therapy increased
      from 12% (57 of 492) to 22% (94 of 437) (OR 2.05, 95% CI 1.42-2.96). The median
      time from enrolment to antiretroviral therapy initiation reduced from 48 days to
      20 days (p<0.0001), primarily because of a reduction in the median time taken to
      complete CD4 staging, which decreased from 32 days to 3 days (p<0.0001). Loss to
      follow-up between staging and antiretroviral therapy initiation did not change
      significantly (OR 0.84, 95% CI 0.49-1.45). INTERPRETATION: Point-of-care CD4
      testing enabled clinics to stage patients rapidly on-site after enrolment, which
      reduced opportunities for pretreatment loss to follow-up. As a result, more
      patients were identified as eligible for and initiated antiretroviral treatment.
      Point-of-care testing might therefore be an effective intervention to reduce
      pretreatment loss to follow-up. FUNDING: Absolute Return for Kids and UNITAID.

PMID- 21951657
TI  - Functional morphology of anal sphincter complex unveiled by high definition anal
      manometery and three dimensional ultrasound imaging.
AB  - BACKGROUND: Anal sphincter complex consists of anatomically overlapping internal
      anal sphincter (IAS), external anal sphincter (EAS) and puborectalis muscle
      (PRM). We determined the functional morphology of anal sphincter muscles using
      high definition anal manometery (HDAM), three dimensional (3D)-ultrasound (US)
      and Magnetic resonance (MR) imaging. METHODS: We studied 15 nulliparous women.
      High definition anal manometery probe equipped with 256 pressure transducers was
      used to measure the anal canal pressures at rest and squeeze. Lengths of IAS,
      PRM, and EAS were determined from the 3D-US images and superimposed on the HDAM
      plots. Movements of anorectal angle with squeeze were determined from the dynamic
      MR images. KEY RESULTS: High definition anal manometery plots reveal that anal
      canal pressures are highly asymmetric in the axial and circumferential direction.
      Anal canal length determined by the 3D-US images is slightly smaller than that
      measured by HDAM. The EAS (1.9 +/- 0.5 cm long) and PRM (1.7 +/- 0.4 cm long)
      surround distal and proximal parts of the anal canal, respectively. With
      voluntary contraction, anal canal pressures increase in the proximal (PRM) and
      distal (EAS zone) parts of anal canal. Posterior peak pressure in the anal canal
      moves cranially in relation to the anterior peak pressure, with squeeze. Similar
      to the movement of peak posterior pressure, MR images show cranial movement of
      anorectal angle with squeeze. CONCLUSIONS & INFERENCES: Our study proves that the
      PRM is responsible for the closure of the cranial part of anal canal. HDAM, in
      addition to measuring constrictor function can also record the elevator function
      of levator ani/pelvic floor muscles.

PMID- 21951658
TI  - TheInternational Index of Erectile Function (IIEF-15): psychometric properties of
      the Portuguese version.
AB  - INTRODUCTION: The International Index of Erectile Function (IIEF) is a brief,
      reliable, and multidimensional scale for assessing sexual function in men in both
      research and clinical trials. AIM: The objective of the present study was to
      determine the psychometric properties of the Portuguese version of the IIEF.
      METHODS: A total of 1,363 Portuguese men participated in this study (a clinical
      sample of 37 men and a community sample of 1,326 men). MAIN OUTCOME MEASURES: All
      participants completed a questionnaire regarding demographic information and the
      IIEF. RESULTS: Principal component analysis using varimax rotation indicated a
      two-factor structure explaining approximately 55% of the total variance (one
      factor encompassing erection and orgasmic function domains of the original IIEF,
      and a second factor corresponding to sexual desire, intercourse, and overall
      satisfaction). The differentiated factor structure with five separate domains of
      sexual function was not replicated in the Portuguese version. The two-factor
      model and the original five-factor model of male sexual function were assessed
      with confirmatory factor analysis (CFA), and overall acceptable fits were
      demonstrated for both models. However, despite a non-optimal performance, CFA
      provided a better support for the five-factor solution as the model that best
      fitted the data. An important lack of discriminant validity evidenced by high
      intercorrelations among dimensions was detected in both models, suggesting a
      substantial overlap among factors. Reliability studies showed good internal
      consistency for the five subscales, and test-retest reliability analysis
      supported the stability of the measure over time. Discriminant validity confirmed
      the ability of both subscales to differentiate men with erectile dysfunction from
      matched controls. CONCLUSIONS: Results suggested that the Portuguese version of
      the IIEF has adequate psychometric properties, and its use is recommended for
      clinical and research purposes. Further studies are needed in order to elucidate
      the association among dimensions of male sexual function and, ultimately, to
      offer a clearer conceptualization of male's sexual response.

PMID- 21951659
TI  - Anteroposterior chest radiograph vs. chest CT scan in early detection of
      pneumothorax in trauma patients.
AB  - Pneumothorax is a common complication following blunt chest wall trauma. In
      these patients, because of the restrictions regarding immobilization of the
      cervical spine, Anteroposterior (AP) chest radiograph is usually the most
      feasible initial study which is not as sensitive as the erect chest X-ray or CT
      chest for detection of a pneumothorax. We will present 3 case reports which serve
      for better understanding of the entity of occult pneumothorax. The first case is
      an example of a true occult pneumothorax where an initial AP chest X-ray revealed
      no evidence of pneumothorax and a CT chest immediately performed revealed
      evidence of pneumothorax. The second case represents an example of a missed
      rather than a truly occult pneumothorax where the initial chest radiograph
      revealed clues suggesting the presence of pneumothorax which were missed by the
      reading radiologist. The third case emphasizes the fact that "occult pneumothorax
      is predictable". The presence of subcutaneous emphesema and pulmonary contusion
      should call for further imaging with CT chest to rule out pneumothorax. Thoracic
      CT scan is therefore the "gold standard" for early detection of a pneumothorax in
      trauma patients. This report aims to sensitize readers to the entity of occult
      pneumothorax and create awareness among intensivists and ER physicians regarding
      the proper diagnosis and management.

PMID- 21951661
TI  - Women's knowledge about cervical cancer risk factors, screening, and reasons for
      non-participation in cervical cancer screening programme in Estonia.
AB  - BACKGROUND: The attendance rate in Estonian cervical cancer screening programme
      is too low therefore the programme is hardly effective. A cross-sectional
      population based survey was performed to identify awareness of cervical cancer
      risk factors, reasons why women do not want to participate in cervical screening
      programme and wishes for better organisation of the programme. METHOD: An
      anonymous questionnaire with a covering letter and a prepaid envelope was sent
      together with the screening invitation to 2942 randomly selected women. Results
      are based on the analysis of 1054 (36%) returned questionnaires. RESULTS: Main
      reasons for non-participation in the national screening programme were a recent
      visit to a gynaecologist (42.3%), fear to give a Pap-smear (14.3%), long
      appointment queues (12.9%) and unsuitable reception hours (11.8%). Fear to give a
      Pap-smear was higher among women aged 30 and 35 than 50 and 55 (RR 1.46; 95% CI:
      0.82-2.59) and women with one or no deliveries (RR 1.56, 95% CI: 0.94-2.58). In
      general, awareness of cervical cancer risk factors is poor and it does not depend
      on socio-demographic factors. Awareness of screening was higher among Estonians
      than Russians (RR 1.64, 95% CI: 1.46-1.86). Most women prefer to receive
      information about screening from personally mailed invitation letters (74.8%).
      CONCLUSIONS: Women need more information about cervical cancer risk factors and
      the screening programme. They prefer personally addressed information sharing.
      Minority groups should be addressed in their own language. A better collaboration
      with service providers and discouraging smears outside the programme are also
      required.

PMID- 21951660
TI  - Structural and biochemical characterization of the inhibitor complexes of
      xenotropic murine leukemia virus-related virus protease.
AB  - Interactions between the protease (PR) encoded by the xenotropic murine leukemia
      virus-related virus and a number of potential inhibitors have been investigated
      by biochemical and structural techniques. It was observed that several inhibitors
      used clinically against HIV PR exhibit nanomolar or even subnanomolar values of
      K(i) , depending on the exact experimental conditions. Both TL-3, a universal
      inhibitor of retroviral PRs, and some inhibitors originally shown to inhibit
      plasmepsins were also quite potent, whereas inhibition by pepstatin A was
      considerably weaker. Crystal structures of the complexes of xenotropic murine
      leukemia virus-related virus PR with TL-3, amprenavir and pepstatin A were solved
      at high resolution and compared with the structures of complexes of these
      inhibitors with other retropepsins. Whereas TL-3 and amprenavir bound in a
      predictable manner, spanning the substrate-binding site of the enzyme, two
      molecules of pepstatin A bound simultaneously in an unprecedented manner, leaving
      the catalytic water molecule in place.

PMID- 21951663
TI  - Tenascin-C is expressed in abdominal aortic aneurysm tissue with an active
      degradation process.
AB  - Abdominal aortic aneurysm (AAA) is a common disease caused by segmental weakening
      of the aortic walls and progressive aortic dilation leading to the eventual
      rupture of the aorta. Currently no biomarkers have been established to indicate
      the disease status of AAA. Tenascin-C (TN-C) is a matricellular protein that is
      synthesized under pathological conditions. In the current study, we related TN-C
      expression to the clinical course and the histopathology of AAA to investigate
      whether the pattern of TN-C expression could indicate the status of AAA. We found
      that TN-C and matrix metalloproteinase (MMP)-9 were highly expressed in human
      AAA. In individual human AAA TN-C deposition associated with the tissue
      destruction, overlapped mainly with the smooth muscle actin-positive cells, and
      showed a pattern distinct from macrophages and MMP-9. In the mouse model of AAA
      high TN-C expression was associated with rapid expansion of the AAA diameter.
      Histological analysis revealed that TN-C was produced mainly by vascular smooth
      muscle cells and was deposited in the medial layer of the aorta during tissue
      inflammation and excessive destructive activities. Our findings suggest that TN-C
      may be a useful biomarker for indicating the pathological status of smooth muscle
      cells and interstitial cells in AAA.

PMID- 21951664
TI  - RUNX2 expression in developing human bones and various bone tumors.
AB  - The heterozygous germline mutation of runt-related protein 2 (RUNX2) causes
      cleidocranial dysplasia. To clarify the involvement of RUNX2 in human
      osteogenesis, fetal bones and various bone tumors were immunohistochemically
      examined. During both membranous and endochondral ossification in the fetus (n=
      8), RUNX2 was expressed not only in osteoblastic cells but also in surrounding
      mesenchymal cells and early stage chondrocytes. Such an expression pattern was
      recapitulated in bone tumors: RUNX2 was unequivocally expressed in osteosarcoma
      (n= 20) and fibrous dysplasia (n= 10), regardless of the site of occurrence, cell
      morphology or amount of neoplastic osteoid. RUNX2 expression was limited to less
      differentiated cells in chondrogenic tumors (n= 20). We further analyzed whether
      RUNX2 expression was regulated by bone morphogenetic protein-2 (BMP-2), which is
      critical for osteoblastic differentiation. With real-time polymerase chain
      reaction, the RUNX2 mRNA level was correlated with BMP-2 mRNA level, and both
      levels were significantly higher in three osteosarcoma cell lines than in three
      chondrosarcoma cell lines. With treatment of recombinant BMP-2, the RUNX2 mRNA
      level was significantly altered in these cell lines. RUNX2 expression is
      constitutive in developing and neoplastic human osteogenesis, and is most likely
      to be regulated by BMP-2.

PMID- 21951665
TI  - Greater age and hepatocellular aging are independent risk factors for
      hepatocellular carcinoma arising from non-B non-C non-alcoholic chronic liver
      disease.
AB  - We previously reported that hepatocellular aging can be assessed by measuring the
      nuclear size of hepatocytes. We attempted to elucidate whether this method is
      useful to identify the high risk group of hepatocellular carcinoma (HCC) in the
      patients with non-B non-C non-alcoholic liver injury. Fourteen patients with HCC
      and 78 without HCC, both of whom presented with non-B non-C non-alcoholic chronic
      liver injury and underwent liver biopsy, were selected. Twelve histologically
      normal liver tissues were selected as controls. The relative nuclear size (RNS)
      was calculated as the average nuclear size of the hepatocytes divided by that of
      lymphocytes. Multiple clinicopathological parameters were studied. The RNS values
      of normal livers ranged from 1.32 to 2.10, showing a gradual increase in an age
      dependent manner. The RNS values of the injured livers without HCC increased
      after middle age. Univariate analysis identified greater age, existence of
      diabetes and RNS, as significantly positive contributors and ALT value and the
      degree of steatosis as negative contributors for the occurrence of HCC. Only age
      and RNS retained significance in multivariate analysis. All of the HCC patients
      were older than 50 and showed RNS values higher than 2.00. Therefore, such
      patients are classified as a high risk group of HCC.

PMID- 21951666
TI  - Squamous cell components in a thyroid follicular adenoma: significant evidence of
      follicular cell origin by histomorphological, immunohistochemical and molecular
      analyses.
AB  - Squamous cells in the thyroid appear in a variety of conditions, including
      adenomatous goiters, malignant neoplasms, inflammatory diseases, and embryonic
      remnants. However the origin of the squamous cells is still under dispute. Here
      we report a case of an encapsulated follicular cell tumor consisting of
      follicular cells, basaloid squamous cells, and morphologically intermediate
      cells. The patient was a 66-year-old man presenting with a progressively enlarged
      painless lump in the right side of his neck. A solid tumor with encapsulation in
      the right lobe was confirmed by simple right lobe thyroid lobectomy. This tumor
      demonstrated heterogeneous immunoreactions for Ki-67, thyroglobulin, thyroid
      transcription factor-1, and pan-cytokeratin (AE1/AE3), in that the intermediate
      cells had intermediate immunoreactivity between follicular and basaloid squamous
      cells. p63 was positive in the periphery layer of tumor cell nests of the
      intermediate and squamous cells. A completely negative immunoreaction was noted
      for high molecular weight cytokeratin (34betaE12), calcitonin, CEA, p53, CD5, and
      rearranged in transformation (RET). Mutational analysis of BRAF and RAS were
      negative. These results strongly suggest that this tumor is a follicular adenoma,
      and that the squamous component originated from follicular cells undergoing
      squamous metaplasia. The patient has been disease free more than 40 months after
      surgery.

PMID- 21951667
TI  - Metaplastic breast carcinoma: a case report and systematic review of the
      literature.
AB  - A 78-year-old retired woman was diagnosed with metaplastic breast carcinoma
      (MBC), a rare tumor, in our hospital. We reviewed 15 articles with a total of
      1328 patients to determine the epidemiology, clinical features, biomarkers,
      histology, management and outcome of patients with this tumor. The mean age at
      presentation is 58.5 years (range 32-83). Eighty-one percent of patients
      presented either with a breast mass or abnormal mammographic finding. Twenty
      three percent of patients had a family history of breast cancer. Estrogen
      receptors were only found in 12%, progesterone receptors in 10% and HER2 in 6% of
      patients. The main method of treatment was mastectomy (66.9%) in combination with
      chemotherapy (57%) and radiotherapy (47%). Five-year disease-free survival ranged
      between 40% and 84% and 5-year overall survival ranged between 64 and 83%. We
      have further reviewed the nature of this disease in the light of advancement in
      genetics, such as microarray gene expression profiling. The relationship of MBC
      with triple-negative tumor and basal-like tumor is discussed. It is hoped that
      advances in genetics and biomarkers will bring forward the era of personalized
      medicine in the treatment of breast carcinoma.

PMID- 21951668
TI  - Thyroid papillary carcinoma with solid sclerosing change in IgG4-related
      sclerosing disease.
AB  - IgG4-related sclerosing disease (IgG4-RSD) is an inflammatory and fibrosing
      disorder characterized by lymphoplasmacytic inflammation with infiltration of
      various organs, including the pancreas, bile ducts, lung, kidney, and
      retroperitoneum. As for malignancy in IgG4-RSD, only limited literature is
      available. We report here a case of thyroid papillary carcinoma showing unique
      morphology in IgG4-RSD. Solid tumor nests were surrounded by dense IgG4-positive
      plasma cells and fibrosis at both the primary site and metastatic lymph nodes. In
      contrast the background thyroid showed focal lymphocytic thyroiditis. IgG4
      related sclerosing sialadenitis and autoimmune pancreatitis were also diagnosed,
      and prednisolone treatment improved symptoms and serum IgG4 abnormality. To the
      best of our knowledge, this is the first documentation of a malignancy of the
      thyroid gland occurring in a background of IgG4-RSD. A brief review of the
      literature on the relationship between IgG4 and malignancy is included.

PMID- 21951669
TI  - Tumor-to-tumor metastasis: Hepatocellular carcinoma metastatic to parathyroid
      adenoma.
AB  - Tumor-to-tumor metastasis is a rare, but well-recognized phenomenon. Here, we
      report a unique case of hepatocellular carcinoma (HCC) metastatic to parathyroid
      adenoma. A 53-year-old-man with a history of HCC presented with hypercalcemia. It
      was found that he also had hyperparathyroidism with a hypoechoic mass in the
      lower portion of the right thyroid gland area. The patient underwent
      parathyroidectomy, and a mass measuring 1.5 * 1.0 cm was detected. Microscopic
      and immunohistochemical examination disclosed parathyroid adenoma with a focus of
      metastatic HCC. For the patient, it was the only distant metastasis revealed
      until the last follow-up. To the best of our knowledge, this is the first
      reported case of tumor-to-tumor metastasis in which HCC is the donor.

PMID- 21951670
TI  - Pituicytoma with unusual histological features.
AB  - Pituicytoma is a rare low-grade glial neoplasm that originates in the
      neurohypophysis or infundibulum. Because of its rare occurrence, the morphology
      and differentiation of pituicytoma have not been fully clarified. Here, we report
      a case of pituicytoma with unusual histological features mimicking ependymoma,
      but exhibiting the diverse morphology and differentiation of pituicytoma. The 1.4
      cm-sized suprasellar mass was incidentally found in the magnetic resonance image
      of a 42-year-old Korean woman who had had a traffic accident. Four years later,
      she presented with symptoms of hypopituitarism and the follow-up images revealed
      slight enlargement of the mass. After gross total resection, microscopic
      examination revealed oval to elongated cells with abundant eosinophilic cytoplasm
      arranged in a perivascular pseudorosette pattern and short interlacing fascicles.
      Pleomorphic tumor cells and Herring bodies were diffusely distributed within the
      tumor. Neither Rosenthal fibers nor eosinophilic granular bodies were identified.
      The tumor cells were immunohistochemically positive for glial fibrillary acidic
      protein, vimentin and S-100 protein, but negative for synaptophysin and
      adenohypophyseal hormones. The epithelial membrane antigen and CD99 were
      expressed with a paranuclear dot-like or membranous pattern in some tumor cells.
      Ultrastructural examination revealed that the tumor cells with intermediate
      filaments were closely apposed with intercellular junctions and frequent basal
      lamina production.

PMID- 21951671
TI  - Ductal adenocarcinoma of the pancreas with psammomatous calcification: report of
      a case with immunohistochemical study for bone morphogenetic protein.
AB  - We report a case of invasive ductal adenocarcinoma of the pancreas with
      psammomatous calcification. A 57-year-old man was admitted to our hospital
      complaining of abdominal pain and vomiting. Carcinoma of the head of the pancreas
      was diagnosed based on precise clinical examinations. A subtotal stomach
      preserving pancreaticoduodenectomy was subsequently performed. Histological
      examination of the surgical specimen revealed a well-differentiated
      adenocarcinoma composed of irregular tubular structures involving the head of the
      pancreas. Conspicuously, numerous tiny psammomatous-type calcifications were
      observed, mainly within the neoplastic lumen, but also in association with
      carcinoma cells that had infiltrated the lymphatics and lymph nodes. In addition,
      expression of bone morphogenetic protein, cartilage and bone-inducing factor
      cloned from demineralized bone matrix and the transforming growth factor-beta
      subfamily was immunohistochemically examined for carcinoma cells. Reactivity for
      multiple kinds of bone morphogenetic protein (types 5, 6 and 7) was identified in
      the cytoplasm of carcinoma cells. Psammoma body formation is an unusual event in
      invasive ductal adenocarcinoma of the pancreas, with only one similar case
      previously reported in the English literature. We also discuss the formation of
      psammomatous calcifications by pancreatic cancer cells.

PMID- 21951672
TI  - Mixed adenoneuroendocrine carcinoma (MANEC) of the gallbladder: a possible stem
      cell tumor?
AB  - A 48 year-old African American woman presented to her physician complaining of a
      rapidly evolving epigastric and right upper quadrant abdominal pain. A PET-CT of
      the abdomen and pelvis demonstrated hypermetabolic, polypoid masses within the
      gallbladder and several tumors in the left lobe of the liver for which she
      underwent diagnostic laparoscopy. The gallbladder revealed a 3.5 * 3.3 * 2.4 tan
      brown exophytic mass located at the fundus and growing into the lumen with
      multiple contiguous papillary projections arising from the mucosal surface. A
      concurrent large cell neuroendocrine carcinoma and papillary adenocarcinoma of
      the gallbladder was revealed histologically. There was shared reactivity to
      antibodies directed against the distinct antigens for each morphological
      component with transitional tumor cells (of both histological components) located
      at the areas where the two tumor types merged, revealing common immunoreactivity
      for carcinoembryonic antigen, cancer antigen 19-9, keratin 19, c-kit (cluster of
      differentiation protein 117 (CD117)) and epithelial cell adhesion molecule.
      Ultrastructurally, individual cells were demonstrated to have overlapping
      features of neuroendocrine and glandular differentiation. The aforementioned
      histological, ultrastructural and immunohistochemical profile is strongly
      suggestive of a biphenotypic stem/progenitor cell tumor of the gallbladder.

PMID- 21951673
TI  - Massive myoepithelial proliferation (myoepitheliosis) with lumpy deposits of
      basement membrane material closely associated with apocrine adenosis and ductal
      carcinoma in situ of the breast.

PMID- 21951674
TI  - Determination of foetal sex in pregnancies at risk of haemophilia: a qualitative
      study exploring the clinical practices and attitudes of health professionals in
      the United Kingdom.
AB  - In pregnancies at risk of haemophilia, foetal sex determination is used to plan
      perinatal management and to guide the offer of invasive testing in pregnancies
      with a male foetus. Traditionally ultrasound from 12 weeks gestation has been
      used, but recently options for early foetal sex determination have increased
      following the introduction of non-invasive prenatal diagnosis (NIPD) using cell
      free foetal DNA in maternal plasma. This study was conducted to identify clinical
      practices and examine health professional attitudes regarding NIPD for foetal sex
      determination. A qualitative approach using one-to-one semi structured interviews
      was used to enable an in-depth exploration of current practice, introduction and
      use of NIPD and benefits and disadvantages of offering NIPD. Interviews were
      conducted with consultant haematologists (N = 7), specialist haemophilia nurses
      (N = 7), genetic counsellors (N = 6), consultants in clinical genetics (N = 5),
      specialist midwives (N = 2) and obstetricians (N = 5) from 24 services across the
      United Kingdom (UK). Key differences in how NIPD for foetal sexing is utilized
      throughout the UK were identified. Some services routinely offered NIPD to all
      carriers of haemophilia or to all carriers of severe haemophilia, others
      discussed the value of NIPD with all or primarily offered NIPD as a first step to
      invasive testing. This study informs our understanding of how NIPD is being
      utilized and provides unique insights into current practice. The identification
      of variation between services in how prenatal testing options are offered has
      implications for future policy and guidelines for prenatal care.

PMID- 21951675
TI  - Parallel ecological diversification in Antarctic notothenioid fishes as evidence
      for adaptive radiation.
AB  - Antarctic notothenioid fishes represent a rare example of a marine species flock.
      They evolved special adaptations to the extreme environment of the Southern Ocean
      including antifreeze glycoproteins. Although lacking a swim bladder,
      notothenioids have diversified from their benthic ancestor into a wide array of
      water column niches, such as epibenthic, semipelagic, cryopelagic and pelagic
      habitats. Applying stable carbon (C) and nitrogen (N) isotope analyses to gain
      information on feeding ecology and foraging habitats, we tested whether
      ecological diversification along the benthic-pelagic axis followed a single
      directional trend in notothenioids, or whether it evolved independently in
      several lineages. Population samples of 25 different notothenioid species were
      collected around the Antarctic Peninsula, the South Orkneys and the South
      Sandwich Islands. The C and N stable isotope signatures span a broad range (mean
      delta(13) C and delta(15) N values between -25.40/00 and -21.90/00 and between
      8.50/00 and 13.80/00, respectively), and pairwise niche overlap between four
      notothenioid families was highly significant. Analysis of isotopic disparity
      through-time on the basis of Bayesian inference and maximum-likelihood
      phylogenies, performed on a concatenated mitochondrial (cyt b) and nuclear gene
      (myh6, Ptr and tbr1) data set (3148 bp), showed that ecological diversification
      into overlapping feeding niches has occurred multiple times in parallel in
      different notothenioid families. This convergent diversification in habitat and
      trophic ecology is a sign of interspecific competition and characteristic for
      adaptive radiations.

PMID- 21951676
TI  - The intriguing evolutionary dynamics of plant mitochondrial DNA.
AB  - The mitochondrial genome of plants is-in every respect and for yet unclear
      reasons-very different from the well-studied one of animals. Thanks to next
      generation sequencing technologies, Davila et al. precisely characterized the
      role played by recombination and DNA repair in controlling mitochondrial
      variations in Arabidopsis thaliana, thus opening new perspectives on the long
      term evolution of this intriguing genome.

PMID- 21951677
TI  - From Leonardo to da Vinci: the history of robot-assisted surgery in urology.
AB  - What's known on the subject? and What does the study add? Numerous urological
      procedures can now be performed with robotic assistance. Though not definitely
      proven to be superior to conventional laparoscopy or traditional open surgery in
      the setting of a randomised trial, in experienced centres robot-assisted surgery
      allows for excellent surgical outcomes and is a valuable tool to augment modern
      surgical practice. Our review highlights the depth of history that underpins the
      robotic surgical platform we utilise today, whilst also detailing the current
      place of robot-assisted surgery in urology in 2011. The evolution of robots in
      general and as platforms to augment surgical practice is an intriguing story that
      spans cultures, continents and centuries. A timeline from Yan Shi (1023-957 bc),
      Archytas of Tarentum (400 bc), Aristotle (322 bc), Heron of Alexandria (10-70
      ad), Leonardo da Vinci (1495), the Industrial Revolution (1790), 'telepresence'
      (1950) and to the da Vinci((r)) Surgical System (1999), shows the incredible
      depth of history and development that underpins the modern surgical robot we use
      to treat our patients. Robot-assisted surgery is now well-established in Urology
      and although not currently regarded as a 'gold standard' approach for any
      urological procedure, it is being increasingly used for index operations of the
      prostate, kidney and bladder. We perceive that robotic evolution will continue
      infinitely, securing the place of robots in the history of Urological surgery.
      Herein, we detail the history of robots in general, in surgery and in Urology,
      highlighting the current place of robot-assisted surgery in radical
      prostatectomy, partial nephrectomy, pyeloplasty and radical cystectomy.

PMID- 21951678
TI  - Comparative safety, immunogenicity, and efficacy of several anti-H5N1 influenza
      experimental vaccines in a mouse and chicken models (Testing of killed and live
      H5 vaccine).
AB  - OBJECTIVE: Parallel testing of inactivated (split and whole virion) and live
      vaccine was conducted to compare the immunogenicity and protective efficacy
      against homologous and heterosubtypic challenge by H5N1 highly pathogenic avian
      influenza virus. METHOD: Four experimental live vaccines based on two H5N1
      influenza virus strains were tested; two of them had hemagglutinin (HA) of
      A/Vietnam/1203/04 strain lacking the polybasic HA cleavage site, and two others
      had hemagglutinins from attenuated H5N1 virus A/Chicken/Kurgan/3/05, with amino
      acid substitutions of Asp54/Asn and Lys222/Thr in HA1 and Val48/Ile and
      Lys131/Thr in HA2 while maintaining the polybasic HA cleavage site. The
      neuraminidase and non-glycoprotein genes of the experimental live vaccines were
      from H2N2 cold-adapted master strain A/Leningrad/134/17/57 (VN-Len and Ku-Len) or
      from the apathogenic H6N2 virus A/Gull/Moscow/3100/2006 (VN-Gull and Ku-Gull).
      Inactivated H5N1 and H1N1 and live H1N1 vaccine were used for comparison. All
      vaccines were applied in a single dose. Safety, immunogenicity, and protectivity
      against the challenge with HPAI H5N1 virus A/Chicken/Kurgan/3/05 were estimated.
      RESULTS: All experimental live H5 vaccines tested were apathogenic as determined
      by weight loss and conferred more than 90% protection against lethal challenge
      with A/Chicken/Kurgan/3/05 infection. Inactivated H1N1 vaccine in mice offered no
      protection against challenge with H5N1 virus, while live cold-adapted H1N1
      vaccine reduced the mortality near to zero level. CONCLUSIONS: The high yield,
      safety, and protectivity of VN-Len and Ku-Len made them promising strains for the
      production of inactivated and live vaccines against H5N1 viruses.

PMID- 21951679
TI  - Development and multiplexing of microsatellite markers using pyrosequencing in
      the clonal plant Comarum palustre (Rosaceae).
AB  - Microsatellites represent one of the most commonly used genetic markers for
      population genetic studies. Traditionally, their development is quite time
      consuming, requiring construction of a genomic library enriched for repeated
      motifs. Using pyrosequencing, a fast and cost-effective new generation sequencing
      technique, we produced 24,340,862 bases in 63,860 short fragment reads, including
      1170 dinucleotide motifs with a minimum of six repeats and 1383 trinucleotide
      motifs with a minimum of four repeats for the Marsh Cinquefoil, Comarum palustre
      L., an endangered marsh pioneer species. We selected 58 loci with SSR (Short
      Sequence Repeat) segments (at least 10 repeats) for a preliminary screening. Out
      of them, we screened 29 loci on a capillary sequencer after ligation in a vector
      and PCR using T7 forward primer labelled with FAM fluorescent dye and the
      specific unlabeled reverse primers. This procedure allowed us to screen large
      number of candidate loci with the same labelled primer and unlabelled specific
      primers. Finally, we characterized 20 polymorphic microsatellite markers, nine
      dinucleotides and 11 trinucleotides. We used these markers to assess genetic
      diversity and clonal structure in two Belgian populations. All loci showed a
      maximum of two alleles per individual, suggesting that they are from a diploid
      genome. One genet was detected in a newly extending population while 53 different
      genets in a long-term ecologically managed population. The number of alleles per
      locus ranged from 6 to 14 in this old population with an expected heterozygosity,
      ranging from 0.5964 to 0.8278. These preliminary results show a genet size up to
      7.2 m.

PMID- 21951680
TI  - At the crossroads of chemistry and cell biology: inhibiting membrane traffic by
      small molecules.
AB  - Intracellular membrane traffic regulates cell physiology at multiple levels
      ranging from cell growth and development to the function of the nervous and
      immune systems. Multiple endocytic routes are used by distinct cargoes including
      ligands bound to their receptors but also viruses and pathogens to gain access to
      the cell interior. Within the endosomal system, proteins and lipids are sorted
      for degradation or recycling allowing cells to dynamically respond to
      environmental signals and to regulate cell shape and morphology. Some receptors
      or toxins are sorted along the retrograde pathway from endosomes to the Golgi
      complex, where they intersect with secretory cargo destined for exocytosis.
      Genetic manipulations of these pathways frequently cause problems with regard to
      data interpretation as the resulting phenotypes may be indirect consequences
      resulting from perturbation of multiple steps or trafficking routes. Hence, novel
      approaches are needed to acutely and reversibly perturb intracellular membrane
      traffic, e.g., by small molecule inhibitors. Such drugs may also be
      pharmacologically important as they offer new avenues to fight human diseases.
      Here, we provide an overview of the small molecules available to interfere with
      intracellular membrane traffic and outline strategies for future research.

PMID- 21951681
TI  - Anterior versus lateral needle decompression of tension pneumothorax: comparison
      by computed tomography chest wall measurement.
AB  - OBJECTIVES: Recent research describes failed needle decompression in the anterior
      position. It has been hypothesized that a lateral approach may be more
      successful. The aim of this study was to identify the optimal site for needle
      decompression. METHODS: A retrospective study was conducted of emergency
      department (ED) patients who underwent computed tomography (CT) of the chest as
      part of their evaluation for blunt trauma. A convenience sample of 159 patients
      was formed by reviewing consecutive scans of eligible patients. Six measurements
      from the skin surface to the pleural surface were made for each patient: anterior
      second intercostal space, lateral fourth intercostal space, and lateral fifth
      intercostal space on the left and right sides. RESULTS: The distance from skin to
      pleura at the anterior second intercostal space averaged 46.3 mm on the right and
      45.2 mm on the left. The distance at the midaxillary line in the fourth
      intercostal space was 63.7 mm on the right and 62.1 mm on the left. In the fifth
      intercostal space the distance was 53.8 mm on the right and 52.9 mm on the left.
      The distance of the anterior approach was statistically less when compared to
      both intercostal spaces (p < 0.01). CONCLUSIONS: With commonly available
      angiocatheters, the lateral approach is less likely to be successful than the
      anterior approach. The anterior approach may fail in many patients as well.
      Longer angiocatheters may increase the chances of decompression, but would also
      carry a higher risk of damage to surrounding vital structures.

PMID- 21951682
TI  - Safety and efficacy of bortezomib-melphalan-prednisone-thalidomide followed by
      bortezomib-thalidomide maintenance (VMPT-VT) versus bortezomib-melphalan
      prednisone (VMP) in untreated multiple myeloma patients with renal impairment.
AB  - We assessed efficacy, safety, and reversal of renal impairment (RI) in untreated
      patients with multiple myeloma given bortezomib-melphalan-prednisone-thalidomide
      followed by bortezomib-thalidomide (VMPT-VT) maintenance or bortezomib-melphalan
      prednisone (VMP). Exclusion criteria included serum creatinine >= 2.5 mg/dL. In
      the VMPT-VT/VMP arms, severe RI (estimated glomerular filtration rate [eGFR] <=
      30 mL/min), moderate RI (eGFR 31-50 mL/min), and normal renal function (eGFR > 50
      mL/min), were 6%/7.9%, 24.1%/24.9%, and 69.8%/67.2%, respectively. Statistically
      significant improvements in overall response rates and progression-free survival
      were observed in VMPT-VT versus VMP arms across renal cohorts, except in severe
      RI patients. In the VMPT group, severe RI reduced overall survival (OS). RI was
      reversed in 16/63 (25.4%) patients receiving VMPT-VT versus 31/77 (40.3%)
      receiving VMP. Multivariate analysis showed male sex (P = .022) and moderate RI
      (P = .003) significantly predicted RI recovery. VMP patients achieving renal
      response showed longer OS. In both arms, greater rates of severe hematologic
      adverse events were associated with RI (eGFR < 50 mL/min), however, therapy
      discontinuation rates were unaffected. VMPT-VT was superior to VMP for cases with
      normal renal function and moderate RI, whereas VMPT-VT failed to outperform VMP
      in patients with severe RI, although the relatively low number of cases analyzed
      preclude drawing definitive conclusions. VMPT-VT had no advantage in terms of RI
      reversal over VMP.

PMID- 21951683
TI  - Autologous peripheral blood stem cell transplantation for acute myeloid leukemia.
AB  - We report the results of a prospective, randomized phase 3 trial evaluating
      autologous peripheral blood stem cell transplantation (ASCT) versus intensive
      consolidation chemotherapy in newly diagnosed AML patients in complete remission
      (CR1). Patients with AML (16-60 years) in CR1 after 2 cycles of intensive
      chemotherapy and not eligible for allogeneic SCT were randomized between
      intensive chemotherapy with etoposide and mitoxantrone or ASCT ater high-dose
      cyclophosphamide and busulfan. Of patients randomized (chemotherapy, n = 259;
      ASCT, n = 258), more than 90% received their assigned treatment. The 2 groups
      were comparable with regard to prognostic factors. The ASCT group showed a
      markedly reduced relapse rate (58% vs 70%, P = .02) and better relapse-free
      survival at 5 years (38% vs 29%, P = .065, hazard ratio = 0.82; 95% confidence
      interval, 0.66-1.1) with nonrelapse mortality of 4% versus 1% in the chemotherapy
      arm (P = .02). Overall survival was similar (44% vs 41% at 5 years, P = .86)
      because of more opportunities for salvage with second-line chemotherapy and stem
      cell transplantation in patients relapsing on the chemotherapy arm. This large
      study shows a relapse advantage for ASCT as postremission therapy but similar
      survival because more relapsing patients on the chemotherapy arm were salvaged
      with a late transplantation for relapse. This trial is registered at
      www.trialregister.nl as #NTR230 and #NTR291.

PMID- 21951684
TI  - Erythrocyte membrane changes of chorea-acanthocytosis are the result of altered
      Lyn kinase activity.
AB  - Acanthocytic RBCs are a peculiar diagnostic feature of chorea-acanthocytosis
      (ChAc), a rare autosomal recessive neurodegenerative disorder. Although recent
      years have witnessed some progress in the molecular characterization of ChAc, the
      mechanism(s) responsible for generation of acanthocytes in ChAc is largely
      unknown. As the membrane protein composition of ChAc RBCs is similar to that of
      normal RBCs, we evaluated the tyrosine (Tyr)-phosphorylation profile of RBCs
      using comparative proteomics. Increased Tyr phosphorylation state of several
      membrane proteins, including band 3, beta-spectrin, and adducin, was noted in
      ChAc RBCs. In particular, band 3 was highly phosphorylated on the Tyr-904
      residue, a functional target of Lyn, but not on Tyr-8, a functional target of
      Syk. In ChAc RBCs, band 3 Tyr phosphorylation by Lyn was independent of the
      canonical Syk-mediated pathway. The ChAc-associated alterations in RBC membrane
      protein organization appear to be the result of increased Tyr phosphorylation
      leading to altered linkage of band 3 to the junctional complexes involved in
      anchoring the membrane to the cytoskeleton as supported by coimmunoprecipitation
      of beta-adducin with band 3 only in ChAc RBC-membrane treated with the Lyn
      inhibitor PP2. We propose this altered association between membrane skeleton and
      membrane proteins as novel mechanism in the generation of acanthocytes in ChAc.

PMID- 21951685
TI  - In vivo structure/function and expression analysis of the CX3C chemokine
      fractalkine.
AB  - The CX3C chemokine family is composed of only one member, CX3CL1, also known as
      fractalkine, which in mice is the sole ligand of the G protein-coupled, 7
      transmembrane receptor CX3CR1. Unlike classic small peptide chemokines, CX3CL1 is
      synthesized as a membrane-anchored protein that can promote integrin-independent
      adhesion. Subsequent cleavage by metalloproteases, either constitutive or
      induced, can generate shed CX3CL1 entities that potentially have chemoattractive
      activity. To study the CX3C interface in tissues of live animals, we generated
      transgenic mice (CX3CL1cherry:CX3CR1gfp), which express red and green fluorescent
      reporter genes under the respective control of the CX3CL1 and CX3CR1 promoters.
      Furthermore, we performed a structure/function analysis to differentiate the in
      vivo functions of membrane-tethered versus shed CX3CL1 moieties by comparing
      their respective ability to correct established defects in macrophage function
      and leukocyte survival in CX3CL1-deficient mice. Specifically, expression of
      CX3CL1(105Delta), an obligatory soluble CX3CL1 isoform, reconstituted the
      formation of transepithelial dendrites by intestinal macrophages but did not
      rescue circulating Ly6Clo CX3CR1hi blood monocytes in CX3CR1gfp/gfp mice.
      Instead, monocyte survival required the full-length membrane-anchored CX3CL1,
      suggesting differential activities of tethered and shed CX3CL1 entities.

PMID- 21951686
TI  - Spleen transcriptome response to infection with avian pathogenic Escherichia coli
      in broiler chickens.
AB  - BACKGROUND: Avian pathogenic Escherichia coli (APEC) is detrimental to poultry
      health and its zoonotic potential is a food safety concern. Regulation of
      antimicrobials in food-production animals has put greater focus on enhancing host
      resistance to bacterial infections through genetics. To better define effective
      mechanism of host resistance, global gene expression in the spleen of chickens,
      harvested at two times post-infection (PI) with APEC, was measured using
      microarray technology, in a design that will enable investigation of effects of
      vaccination, challenge, and pathology level. RESULTS: There were 1,101 genes
      significantly differentially expressed between severely infected and non-infected
      groups on day 1 PI and 1,723 on day 5 PI. Very little difference was seen between
      mildly infected and non-infected groups on either time point. Between birds
      exhibiting mild and severe pathology, there were 2 significantly differentially
      expressed genes on day 1 PI and 799 on day 5 PI. Groups with greater pathology
      had more genes with increased expression than decreased expression levels.
      Several predominate immune pathways, Toll-like receptor, Jak-STAT, and cytokine
      signaling, were represented between challenged and non-challenged groups.
      Vaccination had, surprisingly, no detectible effect on gene expression, although
      it significantly protected the birds from observable gross lesions. Functional
      characterization of significantly expressed genes revealed unique gene ontology
      classifications during each time point, with many unique to a particular
      treatment or class contrast. CONCLUSIONS: More severe pathology caused by APEC
      infection was associated with a high level of gene expression differences and
      increase in gene expression levels. Many of the significantly differentially
      expressed genes were unique to a particular treatment, pathology level or time
      point. The present study not only investigates the transcriptomic regulations of
      APEC infection, but also the degree of pathology associated with that infection.
      This study will allow for greater discovery into host mechanisms for disease
      resistance, providing targets for marker assisted selection and advanced drug
      development.

PMID- 21951687
TI  - Comparison of three predictive rules for assessing severity in elderly patients
      with CAP.
AB  - AIM: This study compares the ability of the Pneumonia Severity Index (PSI) and
      the British Thoracic Society CURB-65 and CRB-65 rules in predicting short-term
      mortality among elderly patients with community-acquired pneumonia (CAP).
      METHODS: It is a population-based study including all people over 65 years old
      with a radiographically confirmed CAP in the region of Tarragona (Spain) between
      2002 and 2008. Treatment setting and clinical variables were considered for each
      patient. PSI, CURB-65 and CRB-65 scores were calculated at the moment of
      diagnosis and 30-day mortality was considered as a main dependent variable. The
      rules were compared based on sensitivity, specificity and area under the receiver
      operating characteristic curve (AUC). RESULTS: Of the total 590 CAP cases,
      mortality rate was 13.6% (15.3% in hospitalised and 1.4% in outpatient cases; p =
      0.001). Mortality increased with increasing PSI score (None in class II, 6,9% in
      class III, 14,4% in class IV and 29,5% in class V), CURB-65 score (7.5%, 14.5%,
      26.7%, 53.3% and 100% for scores 1,2,3,4 and 5 respectively) and CRB-65 score
      (6.6%, 26.1%, 40.5% and 50% for scores 1,2,3 and 4 respectively). The three rules
      performed too similarly to predict 30-day mortality, with a ROC area of 0.727
      [95% confidence interval (CI): 0.67-0.79] for the PSI, 0.672 (95% CI: 0.61-0.74)
      for the CURB-65, and 0.719 (95% CI: 0.65-0.78) for the CRB-65. CONCLUSION: Our
      data shows that the analysed rules perform equally well among elderly people with
      CAP which supports the recommendation for using the simplified CRB-65 severity
      score among elderly patients in primary care or emergency visits.

PMID- 21951688
TI  - Fibrocytes in chronic lung disease--facts and controversies.
AB  - Fibrocytes are bone marrow-derived mesenchymal cell precursors, defined primarily
      by their ability to co-express markers of both haematopoietic (e.g. CD45 or
      CXCR4) and stromal (e.g. collagen) lineages. Fibrocytes in culture also have
      ultrastructural cell surface features that distinguish them from other
      leukocytes. Extensive efforts have helped to characterise fibrocytes
      phenotypically and functionally, but it is still unclear exactly how these cells
      contribute to tissue repair and/or pathologic fibrosis. Nevertheless, the varied
      levels of fibrocytes in blood have raised considerable interest as a biomarker of
      disease activity, such as chronic lung diseases, including pulmonary fibrosis,
      asthma and pulmonary hypertension. These cells also may become a novel
      therapeutic target for these difficult to treat disorders. This review will
      briefly summarize the current knowledge about fibrocytes in human lung disease
      and in animal disease models and highlight areas of consensus as well as issues
      that remain controversial to date.

PMID- 21951689
TI  - Double-strand break repair processes drive evolution of the mitochondrial genome
      in Arabidopsis.
AB  - BACKGROUND: The mitochondrial genome of higher plants is unusually dynamic, with
      recombination and nonhomologous end-joining (NHEJ) activities producing
      variability in size and organization. Plant mitochondrial DNA also generally
      displays much lower nucleotide substitution rates than mammalian or yeast
      systems. Arabidopsis displays these features and expedites characterization of
      the mitochondrial recombination surveillance gene MSH1 (MutS 1 homolog), lending
      itself to detailed study of de novo mitochondrial genome activity. In the present
      study, we investigated the underlying basis for unusual plant features as they
      contribute to rapid mitochondrial genome evolution. RESULTS: We obtained evidence
      of double-strand break (DSB) repair, including NHEJ, sequence deletions and
      mitochondrial asymmetric recombination activity in Arabidopsis wild-type and msh1
      mutants on the basis of data generated by Illumina deep sequencing and confirmed
      by DNA gel blot analysis. On a larger scale, with mitochondrial comparisons
      across 72 Arabidopsis ecotypes, similar evidence of DSB repair activity
      differentiated ecotypes. Forty-seven repeat pairs were active in DNA exchange in
      the msh1 mutant. Recombination sites showed asymmetrical DNA exchange within
      lengths of 50- to 556-bp sharing sequence identity as low as 85%. De novo
      asymmetrical recombination involved heteroduplex formation, gene conversion and
      mismatch repair activities. Substoichiometric shifting by asymmetrical exchange
      created the appearance of rapid sequence gain and loss in association with
      particular repeat classes. CONCLUSIONS: Extensive mitochondrial genomic variation
      within a single plant species derives largely from DSB activity and its repair.
      Observed gene conversion and mismatch repair activity contribute to the low
      nucleotide substitution rates seen in these genomes. On a phenotypic level, these
      patterns of rearrangement likely contribute to the reproductive versatility of
      higher plants.

PMID- 21951690
TI  - DNA extraction techniques for DNA barcoding of minute gall-inhabiting wasps.
AB  - DNA extraction from minute hymenopterans and their larvae is difficult and
      challenging because of their small size indicating a low amount of starting
      material. Hence, 11 DNA extraction methods were compared to determine their
      efficacy in isolating DNA. Success of each method was scored on a 2% agarose gel
      after PCR of the cox 1 mitochondrial locus. A silica-membrane-based approach was
      the most successful, followed by a method using a combination of incubation
      buffers and a method using magnetic beads. The method using buffers was the most
      cost- and time effective. Using this method, larvae from Eucalyptus seed capsule
      galls could be assigned a role (parasitoid, gall former or inquiline) in the gall
      inhabiting complex.

PMID- 21951691
TI  - Risk for cancer among men with erectile dysfunction in Taiwan--patient-based or
      population-based?

PMID- 21951692
TI  - Medical interns' knowledge and training regarding urethral catheter insertion and
      insertion-related urethral injury in male patients.
AB  - BACKGROUND: Improper catheterization can lead to urethral injury. Yet research
      from four continents suggests training of junior doctors in catheterization is
      insufficient. European research suggests a majority of catheterization related
      morbidities occur when the procedure is performed by interns. METHODS: To assess
      the knowledge and practices of medical interns relating to urethral
      catheterization and iatrogenic urethral injury secondary to traumatic catheter
      insertion, a questionnaire survey was conducted of all first year medical interns
      at a tertiary national university hospital in the Philippines. The questionnaire
      contained 17 items covering 4 areas: methods of training in catheterization and
      level of experience; perceived adequacy of training; theoretical knowledge of
      catheterization; the mechanisms of catheter-related urethral injury. RESULTS:
      225/240 interns (94%) completed the survey (130 (57.8%) female). 125 (55.6%)
      responded that they had adequate theoretical training and 150 (66.7%) adequate
      practical training. All had performed more than 10 catheterizations and 204 (90%)
      were supervised when they first performed catheterization. Despite relatively
      high levels of experience and confidence, deficits were identified in detailed
      knowledge of correct catheterization procedures and of risks associated with
      urethral injury. CONCLUSIONS: More thorough training of incoming medical interns
      in urinary catheterization may help to reduce the risk of complications and
      injury. Training should be universal and thought given to its timing within the
      curriculum. Training should include step by step instruction in the process,
      emphasis on history taking and awareness of factors associated with increased
      risk of urethral injury.

PMID- 21951693
TI  - Viscosupplementation in haemophilic arthropathy: a long-term follow-up study.
AB  - Haemophilic arthropathy is the most common clinical manifestation of haemophilia,
      secondary to recurrent haemarthroses and chronic synovitis. Modern bleeding
      preventing drugs have limited significantly the incidence of severe arthropathy,
      and primary approach is usually conservative. Use of intra-articular injections
      of hyaluronan acid is considered one of the most efficient treatments for early
      stages of articular degenerative diseases. Assessment of long-term effectiveness
      of intra-articular administration of hyaluronic acid (HA) in knees, ankles and
      elbows of patients affected by haemophilic arthropathy was done for 46 patients
      (10 elbows, 24 knees and 25 ankles) affected by haemophilic arthropathy. They
      received injections of HA and were evaluated with Visual Analogue Scale, Short
      Form-36, World Federation of Haemophilia score and Petterson score with a 6-year
      mean follow-up. Most of the patients showed improvement in pain relief and
      functional recovery without any complications: only a limited number of patients
      (8.6%) found poor results, undergoing surgery or other further treatments in the
      follow-up period for persistent pain or limitation. Viscosupplementation is an
      effective therapeutic strategy in early stages of haemophilic arthropathy, with
      no complications and long-term good clinical results.

PMID- 21951694
TI  - Nomadic sexualities: an in-depth case study about unsafe sex.
AB  - In an era when researchers are identifying increased rates of unsafe sex among
      gay and bisexual men, it is important that the practice of unsafe sex be
      adequately explored. While much literature is already dedicated to this topic,
      only recently have researchers begun to develop in-depth understandings of the
      personal meanings that people ascribe to unsafe sex. This study continues such
      explorations by examining (i) why one self-defined gay man engaged in unsafe sex,
      and (ii) how he defined unsafe sex. The findings suggest that, for this man, his
      sexuality is nomadic and that what he feels is unsafe sex is the outcome of his
      nomadic sexuality conflicting with social imperatives for sexual stratification.

PMID- 21951696
TI  - Assessment of complication and functional outcome reporting in the minimally
      invasive prostatectomy literature from 2006 to the present.
AB  - To query the minimally invasive urological literature from 2006 to the middle of
      2010, focusing on complications and functional outcome reporting in laparoscopic
      radical prostatectomy (LRP) and robot-assisted LRP (RALP), to see if there has
      been an improvement in the overall reporting of complications. We performed a
      Medline search using the Medical Subject Heading terms 'prostatectomy',
      'laparoscopy', 'robotics', and 'minimally invasive'. We then applied the Martin
      criteria for complications reporting to the selected articles. We identified 51
      studies for a total of 32,680 patients. When excluding functional outcomes the
      outpatient complications reporting was 20/51 (39.2%). In all, 35% and 43% of
      papers did not list any method for recording continence and potency,
      respectively. A complication grading system was only used in 30 studies (58.8%).
      Of the 16 papers using a grading scale in 2006-2007, only 31.3% used the Clavien
      system, compared with 69% from 2008 to the first half of 2010. In all, 27% of
      papers used some form of risk-factor analysis for complications. Multivariate
      analysis was used in 43% of papers, 29% looked at body mass index, while one
      looked at prostate weight, and another age. There has been an overall improvement
      in complications reporting in the minimally invasive RP literature since 2005.
      However, most studies still do not fulfil many of the criteria necessary for
      standardised complication reporting. Functional outcome reporting remains poor
      and unstandardised. Given our current reliance on observational studies,
      increased efforts should be made to standardise all complication outcomes
      reporting.

PMID- 21951695
TI  - Membrane interaction of Pasteurella multocida toxin involves sphingomyelin.
AB  - Pasteurella multocida toxin (PMT) is an AB toxin that causes pleiotropic effects
      in targeted host cells. The N-terminus of PMT (PMT-N) is considered to harbor the
      membrane receptor binding and translocation domains responsible for mediating
      cellular entry and delivery of the C-terminal catalytic domain into the host
      cytosol. Previous studies have implicated gangliosides as the host receptors for
      PMT binding. To gain further insight into the binding interactions involved in
      PMT binding to cell membranes, we explored the role of various membrane
      components in PMT binding, utilizing four different approaches: (a) TLC-overlay
      binding experiments with (125) I-labeled PMT, PMT-N or the C-terminus of PMT; (b)
      pull-down experiments using reconstituted membrane liposomes with full-length
      PMT; (c) surface plasmon resonance analysis of PMT-N binding to reconstituted
      membrane liposomes; (d) and surface plasmon resonance analysis of PMT-N binding
      to HEK-293T cell membranes without or with sphingomyelinase, phospholipase D or
      trypsin treatment. The results obtained revealed that, in our experimental
      system, full-length PMT and PMT-N did not bind to gangliosides, including
      monoasialogangliosides GM(1) , GM(2) or GM(3) , but instead bound to membrane
      phospholipids, primarily the abundant sphingophospholipid sphingomyelin or
      phosphatidylcholine with other lipid components. Collectively, these studies
      demonstrate the importance of sphingomyelin for PMT binding to membranes and
      suggest the involvement of a protein co-receptor.

PMID- 21951697
TI  - The effect of age and tongue exercise on BDNF and TrkB in the hypoglossal nucleus
      of rats.
AB  - Age-associated changes in tongue musculature may contribute to dysphagia. One
      possible treatment is tongue exercise. Exercise induces synaptic plasticity by
      increasing neurotrophic factors in spinal cord and limb musculature. However,
      effects of exercise on neurotrophic factors in the cranial sensorimotor system
      are unknown. Our purpose was to examine the effects of age and exercise on brain
      derived neurotrophic factor (BDNF) and its receptor TrkB in the rat hypoglossal
      nucleus. Young, middle-aged, and old rats were assigned to exercise or no
      exercise control conditions. Exercise animals were trained to perform a tongue
      press task for 8 weeks. Samples from the hypoglossal nucleus were analyzed for
      BDNF and TrkB immunoreactivity. Baseline maximum tongue forces were similar in
      all age groups and increased significantly following exercise. BDNF
      immunoreactivity did not show a significant decrease with age in control group.
      However, in the exercise group, BDNF was significantly increased in young
      animals. TrkB immunoreactivity decreased significantly with age in control group,
      but did not change with exercise. BDNF and TrkB immunoreactivity levels were
      positively correlated with exercise in young and middle aged animals, but were
      negatively or weakly correlated with exercise in old animals and with a lack of
      exercise in no-exercise controls. Tongue exercise was associated with increased
      tongue forces in rats at all ages. While increases in BDNF and TrkB levels
      associated with exercise may play a role in mechanisms contributing to increased
      tongue forces in young and middle-aged rats, other mechanisms may be involved in
      increased tongue forces observed in old rats.

PMID- 21951698
TI  - Gene expression during normal and FSHD myogenesis.
AB  - BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is a dominant disease
      linked to contraction of an array of tandem 3.3-kb repeats (D4Z4) at 4q35. Within
      each repeat unit is a gene, DUX4, that can encode a protein containing two
      homeodomains. A DUX4 transcript derived from the last repeat unit in a contracted
      array is associated with pathogenesis but it is unclear how. METHODS: Using exon
      based microarrays, the expression profiles of myogenic precursor cells were
      determined. Both undifferentiated myoblasts and myoblasts differentiated to
      myotubes derived from FSHD patients and controls were studied after
      immunocytochemical verification of the quality of the cultures. To further our
      understanding of FSHD and normal myogenesis, the expression profiles obtained
      were compared to those of 19 non-muscle cell types analyzed by identical methods.
      RESULTS: Many of the ~17,000 examined genes were differentially expressed (>2
      fold, p<0.01) in control myoblasts or myotubes vs. non-muscle cells (2185 and
      3006, respectively) or in FSHD vs. control myoblasts or myotubes (295 and 797,
      respectively). Surprisingly, despite the morphologically normal differentiation
      of FSHD myoblasts to myotubes, most of the disease-related dysregulation was seen
      as dampening of normal myogenesis-specific expression changes, including in genes
      for muscle structure, mitochondrial function, stress responses, and signal
      transduction. Other classes of genes, including those encoding extracellular
      matrix or pro-inflammatory proteins, were upregulated in FSHD myogenic cells
      independent of an inverse myogenesis association. Importantly, the disease-linked
      DUX4 RNA isoform was detected by RT-PCR in FSHD myoblast and myotube preparations
      only at extremely low levels. Unique insights into myogenesis-specific gene
      expression were also obtained. For example, all four Argonaute genes involved in
      RNA-silencing were significantly upregulated during normal (but not FSHD)
      myogenesis relative to non-muscle cell types. CONCLUSIONS: DUX4's pathogenic
      effect in FSHD may occur transiently at or before the stage of myoblast formation
      to establish a cascade of gene dysregulation. This contrasts with the current
      emphasis on toxic effects of experimentally upregulated DUX4 expression at the
      myoblast or myotube stages. Our model could explain why DUX4's inappropriate
      expression was barely detectable in myoblasts and myotubes but nonetheless linked
      to FSHD.

PMID- 21951700
TI  - Serum sex steroids measured in middle-aged European and African-Caribbean men by
      gas chromatography-mass spectrometry.
AB  - BACKGROUND: Differences in circulating steroid hormone levels have been
      hypothesized to explain ethnic differences in steroid-related diseases. The aim
      of this study was to determine the serum levels of a wide panel of steroid
      hormones, both androgens and estrogens, in healthy middle-aged African-Caribbean
      and European men. DESIGN AND METHODS: Serum steroid hormone levels were
      determined in men participating in a systematic public health study funded by the
      French National Health Insurance system. Blood was collected in the morning from
      304 healthy African-Caribbean and European men aged between 40 and 69 years.
      Serum steroids were measured by mass spectrometry-gas chromatography, except for
      DHEAS and sex hormone-binding globulin, which were determined by RIA. Data were
      analyzed in 10-year age intervals by analysis of covariance, with adjustment for
      age, body mass index, waist-to-hip ratio, tobacco and alcohol consumption, and
      season of sampling. RESULTS: Compared with Europeans, African-Caribbean men
      presented significantly higher serum levels of measured bioavailable
      testosterone, 4-androstenedione (4-dione), and estrone (E1) regardless of the age
      group, of 5-androstenediol (5-diol) in those aged 40-49 and 50-59 years, and of
      testosterone (TT) and dihydrotestosterone in those aged 40-49 years. In contrast,
      European men aged 40-69 years showed significantly higher serum levels of DHEA
      and DHEAS. CONCLUSIONS: Significant differences in serum steroid hormone levels
      were observed in middle-aged African-Caribbean and European men. Whether such
      differences could contribute to ethnic differences in disease risk in adult men
      remains to be investigated. Some steroids, such as bioavailable TT, 4-dione, 5
      diol, and E1, deserve particular attention.

PMID- 21951699
TI  - Movement based artifacts may contaminate extracellular electrical recordings from
      GI muscles.
AB  - BACKGROUND: Electrical slow waves drive peristaltic contractions in the stomach
      and facilitate gastric emptying. In gastroparesis and other disorders associated
      with altered gastric emptying, motility defects have been related to altered slow
      wave frequency and disordered propagation. Experimental and clinical measurements
      of slow waves are made with extracellular or abdominal surface recording.
      METHODS: We tested the consequences of muscle contractions and movement on
      biopotentials recorded from murine gastric muscles with array electrodes and
      pairs of silver electrodes. KEY RESULTS: Propagating biopotentials were readily
      recorded from gastric sheets composed of the entire murine stomach. The
      biopotentials were completely blocked by nifedipine (2 MUmol L(-1) ) that blocked
      contractile movements and peristaltic contractions. Wortmannin, an inhibitor of
      myosin light chain kinase, also blocked contractions and biopotentials.
      Stimulation of muscles with carbachol increased the frequency of biopotentials in
      control conditions but failed to elicit biopotentials with nifedipine or
      wortmannin present. Intracellular recording with microelectrodes showed that
      authentic gastric slow waves occur at a faster frequency typically than
      biopotentials recorded with extracellular electrodes, and electrical slow waves
      recorded with intracellular electrodes were unaffected by suppression of
      movement. Electrical transients, equal in amplitude to biopotentials recorded
      with extracellular electrodes, were induced by movements produced by small
      transient stretches (<1 mm) of paralyzed or formalin fixed gastric sheets.
      CONCLUSIONS & INFERENCES: These data demonstrate significant movement artifacts
      in extracellular recordings of biopotentials from murine gastric muscles and
      suggest that movement suppression should be an obligatory control when monitoring
      electrical activity and characterizing propagation and coordination of electrical
      events with extracellular recording techniques.

PMID- 21951701
TI  - Neonatal presentation of familial glucocorticoid deficiency resulting from a
      novel splice mutation in the melanocortin 2 receptor accessory protein.
AB  - BACKGROUND: Familial glucocorticoid deficiency (FGD) is a rare autosomal
      recessive disorder characterised by isolated glucocorticoid deficiency. Mutations
      in the ACTH receptor/melanocortin 2 receptor (MC2R), the MC2R accessory protein
      (MRAP) or the STAR protein (STAR) cause FGD types 1, 2 and 3, respectively,
      accounting for ~50% of all cases. PATIENT AND METHODS: We report a neonate of
      Indian origin, who was diagnosed with FGD in the first few days of life. He
      presented with hypoglycaemic seizures and was noted to have generalised intense
      hyperpigmentation and normal male genitalia. Biochemical investigations revealed
      hypocortisolaemia (cortisol 0.223 MUg/dl; NR 1-23 MUg/dl) and elevated plasma
      ACTH (170 pg/ml). Serum electrolytes, aldosterone and plasma renin activity were
      normal. Peak cortisol following a standard synacthen test was 0.018 MUg/dl. He
      responded to hydrocortisone treatment and continues on replacement. Patient DNA
      was analysed by direct sequencing. The effect of the novel mutation was assessed
      by an in vitro splicing assay using wild type and mutant heterologous minigenes.
      RESULTS: A novel homozygous mutation c.106+2_3dupTA was found in the MRAP gene.
      Both parents were heterozygous for the mutation. In an in vitro splicing assay,
      the mutation resulted in the skipping of exon 3. CONCLUSION: We have identified a
      novel MRAP mutation where disruption of the intron 3 splice-site results in a
      prematurely terminated translation product. This protein (if produced) would lack
      the transmembrane domain that is essential for MC2R interaction. We predict that
      this would cause complete lack of ACTH response thus explaining the early
      presentation in this case.

PMID- 21951702
TI  - Durkheim at the movies: a century of suicide in film.

PMID- 21951704
TI  - Gastrointestinal stromal tumor of the esophagus.

PMID- 21951705
TI  - Type 2 polarized immune response holds a major position in Epstein-Barr virus
      related idiopathic thrombocytopenic purpura (EBV-ITP).
AB  - INTRODUCTION: Dysfunctional cellular immunity is considered to be essential to
      the pathophysiology of Epstein-Barr virus-related idiopathic thrombocytopenic
      purpura (EBV-ITP). Cytokines in peripheral blood and the gene expression of
      transcription factors in T lymphocytes of patients with were investigated to
      correlate the polarization of T helper cell type 1 (Th1)/T helper cell type 2
      (Th2) with the degree of thrombocytopenia. METHODS: The expression of type 1 (T
      bet) and type 2 (GATA-3) in T lymphocytes was detected by semiquantitative
      reverse-transcription-polymerase chain reaction, and plasma cytokine levels were
      measured by enzyme-linked immunoassay in 35 patients and 30 control subjects.
      RESULTS: Th1/Th2 [(interleukin-2 + gamma-interferon)/(interleukin-10 +
      interleukin-13)] cytokine ratios and transcription factor (T-bet/GATA-3) mRNA
      ratios were significantly decreased in patients with EBV-ITP, and the Th1/Th2
      ratio was directly correlated with platelet counts. CONCLUSION: Our findings
      clearly show that type 2 polarization of the autoimmune response accounts for the
      expression of cytokines and transcription factors in EBV-ITP.

PMID- 21951706
TI  - Evidence for morphological and adaptive genetic divergence between lake and
      stream habitats in European minnows (Phoxinus phoxinus, Cyprinidae).
AB  - Natural selection drives local adaptation, potentially even at small temporal and
      spatial scales. As a result, adaptive genetic and phenotypic divergence can occur
      among populations living in different habitats. We investigated patterns of
      differentiation between contrasting lake and stream habitats in the cyprinid fish
      European minnow (Phoxinus phoxinus) at both the morphological and genomic levels
      using geometric morphometrics and AFLP markers, respectively. We also used a
      spatial correlative approach to identify AFLP loci associated with environmental
      variables representing potential selective forces responsible for adaptation to
      divergent habitats. Our results identified different morphologies between lakes
      and streams, with lake fish presenting a deeper body and caudal peduncle compared
      to stream fish. Body shape variation conformed to a priori predictions concerning
      biomechanics and swimming performance in lakes vs. streams. Moreover,
      morphological differentiation was found to be associated with several
      environmental variables, which could impose selection on body and caudal peduncle
      shape. We found adaptive genetic divergence between these contrasting habitats in
      the form of 'outlier' loci (2.9%) whose genetic divergence exceeded neutral
      expectations. We also detected additional loci (6.6%) not associated with habitat
      type (lake vs. stream), but contributing to genetic divergence between
      populations. Specific environmental variables related to trophic dynamics,
      landscape topography and geography were associated with several neutral and
      outlier loci. These results provide new insights into the morphological
      divergence and genetic basis of adaptation to differentiated habitats.

PMID- 21951707
TI  - Mechanism of collapse of endoplasmic reticulum cisternae during African swine
      fever virus infection.
AB  - Infection of cells with African swine fever virus (ASFV) can lead to the
      formation of zipper-like stacks of structural proteins attached to collapsed
      endoplasmic reticulum (ER) cisternae. We show that the collapse of ER cisternae
      observed during ASFV infection is dependent on the viral envelope protein, J13Lp.
      Expression of J13Lp alone in cells is sufficient to induce collapsed ER
      cisternae. Collapse was dependent on a cysteine residue in the N-terminal domain
      of J13Lp exposed to the ER lumen. Luminal collapse was also dependent on the
      expression of J13Lp within stacks of ER where antiparallel interactions between
      the cytoplasmic domains of J13Lp orientated N-terminal domains across ER
      cisternae. Cisternal collapse was then driven by disulphide bonds between N
      terminal domains arranged in antiparallel arrays across the ER lumen. This
      provides a novel mechanism for biogenesis of modified stacks of ER present in
      cells infected with ASFV, and may also be relevant to cellular processes.

PMID- 21951708
TI  - Active and passive MDMA ('ecstasy') intake induces differential transcriptional
      changes in the mouse brain.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') is a recreational drug widely
      used by adolescents and young adults. Although its rewarding effects are well
      established, there is controversy on its addictive potential. We aimed to compare
      the consequences of active and passive MDMA administration on gene expression in
      the mouse brain since all previous studies were based on passive MDMA
      administration. We used a yoked-control operant intravenous self-administration
      paradigm combined with microarray technology. Transcriptomic profiles of ventral
      striatum, frontal cortex, dorsal raphe nucleus and hippocampus were analysed in
      mice divided in contingent MDMA, yoked MDMA and yoked saline groups, and several
      changes were validated by quantitative reverse transcription polymerase chain
      reaction (qRT-PCR). The comparison of contingent MDMA and yoked MDMA vs. yoked
      saline mice allowed the identification of differential expression in several
      genes, most of them with immunological and inflammatory functions, but others
      being involved in neuroadaptation. In the comparison of contingent MDMA vs. yoked
      MDMA administration, hippocampus and the dorsal raphe nucleus showed
      statistically significant changes. The altered expression of several genes
      involved in neuroadaptative changes and synapse function, which may be related to
      learning self-administration behaviour, could be validated in these two brain
      structures. In conclusion, our study shows a strong effect of MDMA administration
      on the expression of immunological and inflammatory genes in all the four brain
      regions studied. In addition, experiments on MDMA self-administration suggest
      that the dorsal raphe nucleus and hippocampus may be involved in active MDMA
      seeking behaviour, and show specific alterations on gene expression that support
      the addictive potential of this drug.

PMID- 21951709
TI  - The role of Candida albicans homologous recombination factors Rad54 and Rdh54 in
      DNA damage sensitivity.
AB  - BACKGROUND: The fungal pathogen Candida albicans is frequently seen in immune
      suppressed patients, and resistance to one of the most widely used antifungals,
      fluconazole (FLC), can evolve rapidly. In recent years it has become clear that
      plasticity of the Candida albicans genome contributes to drug resistance through
      loss of heterozygosity (LOH) at resistance genes and gross chromosomal
      rearrangements that amplify gene copy number of resistance associated genes. This
      study addresses the role of the homologous recombination factors Rad54 and Rdh54
      in cell growth, DNA damage and FLC resistance in Candida albicans. RESULTS: The
      data presented here support a role for homologous recombination in cell growth
      and DNA damage sensitivity, as Candida albicans rad54Delta/rad54Delta mutants
      were hypersensitive to MMS and menadione, and had an aberrant cell and nuclear
      morphology. The Candida albicans rad54Delta/rad54Delta mutant was defective in
      invasion of Spider agar, presumably due to the altered cellular morphology. In
      contrast, mutation of the related gene RDH54 did not contribute significantly to
      DNA damage resistance and cell growth, and deletion of either Candida albicans
      RAD54 or Candida albicans RDH54 did not alter FLC susceptibility. CONCLUSIONS:
      Together, these results support a role for homologous recombination in genome
      stability under nondamaging conditions. The nuclear morphology defects in the
      rad54Delta/rad54Delta mutants show that Rad54 performs an essential role during
      mitotic growth and that in its absence, cells arrest in G2. The viability of the
      single mutant rad54Delta/rad54Delta and the inability to construct the double
      mutant rad54Delta/rad54Delta rdh54Delta/rdh54Delta suggests that Rdh54 can
      partially compensate for Rad54 during mitotic growth.

PMID- 21951710
TI  - The development and psychometric validation of the central sensitization
      inventory.
AB  - Central sensitization (CS) has been proposed as a common pathophysiological
      mechanism to explain related syndromes for which no specific organic cause can be
      found. The term "central sensitivity syndrome (CSS)" has been proposed to
      describe these poorly understood disorders related to CS. The goal of this
      investigation was to develop the Central Sensitization Inventory (CSI), which
      identifies key symptoms associated with CSSs and quantifies the degree of these
      symptoms. The utility of the CSI, to differentiate among different types of
      chronic pain patients who presumably have different levels of CS impairment, was
      then evaluated. Study 1 demonstrated strong psychometric properties (test-retest
      reliability = 0.817; Cronbach's alpha = 0.879) of the CSI in a cohort of
      normative subjects. A factor analysis (including both normative and chronic pain
      subjects) yielded 4 major factors (all related to somatic and emotional
      symptoms), accounting for 53.4% of the variance in the dataset. In Study 2, the
      CSI was administered to 4 groups: fibromyalgia (FM); chronic widespread pain
      without FM; work-related regional chronic low back pain (CLBP); and normative
      control group. Analyses revealed that the patients with FM reported the highest
      CSI scores and the normative population the lowest (P < 0.05). Analyses also
      demonstrated that the prevalence of previously diagnosed CSSs and related
      disorders was highest in the FM group and lowest in the normative group (P <
      0.001). Taken together, these 2 studies demonstrate the psychometric strength,
      clinical utility, and the initial construct validity of the CSI in evaluating CS
      related clinical symptoms in chronic pain populations. 

PMID- 21951711
TI  - Adrenomedullin mediates adipose tissue-derived stem cell-induced restoration of
      erectile function in diabetic rats.
AB  - INTRODUCTION: Erectile dysfunction (ED) is a major health problem. It is known
      that diabetic patients are more refractory to common treatments for ED. AIM: To
      explore the better treatment for ED, we examined the effects of adipose-derived
      stem cells (ASC) on ED using a diabetic rat model. We also analyzed the cytokines
      produced by ASC and implicated in ASC-induced restoration of erectile function.
      METHODS: Male Wistar rats were injected with streptozotocin (STZ) to induce
      diabetes. ASC or adenoviruses were injected into the penis 6 weeks after STZ
      administration. Erectile function, penile histology and protein expression were
      analyzed 4 weeks after the injection of ASC or adenoviruses. MAIN OUTCOME
      MEASURES: Intracavernous pressure and mean arterial pressure were measured to
      evaluate erectile function. The morphology of the penis was analyzed by Elastica
      van Gieson stain and immunohistochemistry. The expression of proteins specific
      for vascular endothelial cells (VEC) was assessed by Western blot analysis.
      RESULTS: ASC restored erectile function especially when they were cultured in
      medium containing growth factors for VEC. This restoration was associated with
      improvement in the histology of the cavernous body, and increased expression of
      VEC markers such as VE-cadherin and endothelial nitric oxide synthase (eNOS).
      When the expression of adrenomedullin (AM), a vasoactive peptide originally
      isolated from human pheochromocytoma tissue, was knocked down, the effect of ASC
      on ED was significantly diminished. Knockdown of AM was associated with decreased
      expressions of VE-cadherin and eNOS. Furthermore, overexpression of AM induced by
      adenovirus infection significantly improved erectile function in these diabetic
      rats. Overexpression of AM was associated with increased expressions of VE
      cadherin and eNOS. CONCLUSIONS: These results suggested that ASC have the
      potentials to restore erectile function and that AM produced by ASC plays a major
      role in the restoration of erectile function.

PMID- 21951713
TI  - An evaluation of the patient education programme for Parkinson's disease in
      clinical practice.
AB  - AIM: The Patient Education Programme for Parkinson's disease (PEPP) was assessed
      in a recent randomised controlled trial (RCT). In this study, a trend was
      identified towards significant improvement of patients' quality of life (Qol) as
      well as a significant reduction of caregivers' psychosocial burden and need for
      help. This study is aimed at evaluating the effectiveness of the PEPP in clinical
      practice as compared with the RCT in an academic setting. The second aim is to
      assess its effectiveness in clinical practice at 6-month follow-up. METHODS:
      Fifty-five patients and 50 caregivers from nine clinical settings participated in
      the PEPP consisting of eight weekly sessions of 90 min. Self-report
      questionnaires were used to assess patients' Qol (PDQ-39) and caregivers'
      psychosocial burden and need for help (BELA-A-k) at baseline, directly after the
      programme and at 6-month follow-up. To compare the baseline data and short-term
      effects, data were used from an RCT study which included 64 Parkinson's disease
      patients and 46 caregivers. RESULTS: Compared with the RCT control group,
      significant effects, after Bonferoni adjustment, were found for patients' Qol as
      well as for caregivers' psychosocial burden and need for help. No significant
      changes were found between baseline scores compared with 6-month follow-up.
      Scores returned to baseline levels at 6-month follow-up. CONCLUSIONS: Effects
      from the RCT study were replicated and the effect on patients' Qol was now
      significant. However, at 6-month follow-up, scores returned to baseline levels,
      indicating the need for some form of a booster session.

PMID- 21951712
TI  - BDE 49 and developmental toxicity in zebrafish.
AB  - The polybrominated diphenyl ethers (PBDEs) are a group of brominated flame
      retardants. Human health concerns of these agents have largely centered upon
      their potential to elicit reproductive and developmental effects. Of the various
      congeners, BDE 49 (2,2',4,5'-tetrabromodiphenyl ether) has been poorly studied,
      despite the fact that it is often detected in the tissues of fish and wildlife
      species. Furthermore, we have previously shown that BDE 49 is a metabolic
      debromination product of BDE 99 hepatic metabolism in salmon, carp and trout,
      underscoring the need for a better understanding of biological effects. In the
      current study, we investigated the developmental toxicity of BDE 49 using the
      zebrafish (Danio rerio) embryo larval model. Embryo and larval zebrafish were
      exposed to BDE 49 at either 5 hours post fertilization (hpf) or 24 hpf and
      monitored for developmental and neurotoxicity. Exposure to BDE 49 at
      concentrations of 4iMU-32 MUM caused a dose-dependent loss in survivorship at 6
      days post fertilization (dpf). Morphological impairments were observed prior to
      the onset of mortality, the most striking of which included severe dorsal
      curvatures of the tail. The incidence of dorsal tail curvatures was dose and time
      dependent. Exposure to BDE 49 caused cardiac toxicity as evidenced by a
      significant reduction in zebrafish heart rates at 6 dpf but not earlier,
      suggesting that cardiac toxicity was non-specific and associated with
      physiological stress. Neurobehavioral injury from BDE 49 was evidenced by an
      impairment of touch-escape responses observed at 5 dpf. Our results indicate that
      BDE 49 is a developmental toxicant in larval zebrafish that can cause
      morphological abnormalities and adversely affect neurobehavior. The observed
      toxicities from BDE 49 were similar in scope to those previously reported for the
      more common tetrabrominated congener, BDE 47, and also for other lower brominated
      PBDEs, suggest that these compounds may share similarities in risk to aquatic
      species.

PMID- 21951714
TI  - Human FAD synthase (isoform 2): a component of the machinery that delivers FAD to
      apo-flavoproteins.
AB  - A soluble form of human FAD synthase (isoform 2; hFADS2) was produced and
      purified to homogeneity as a recombinant His-tagged protein. The enzyme binds 1
      mole of the FAD product very tightly, although noncovalently. Complete release of
      FAD from the 'as isolated' protein requires extensive denaturation. A 75 : 25
      mixture of apo/holoprotein could be prepared by treatment with mild chaotropes,
      allowing estimatation of the contribution made by bound FAD to the protein
      stability and evaluatation of whether structural rearrangements may be required
      for FAD release. Under turnover conditions, the enzyme catalyzes FAD assembly
      from ATP and FMN and, at a much lower rate, the pyrophosphorolytic hydrolysis of
      FAD. Several mechanistic features of both reactions were investigated in detail,
      along with their dependence on environmental conditions (pH, temperature,
      dependence on metals). Our data indicate that FAD release may represent the rate
      limiting step of the whole catalytic cycle and that the process leading to FAD
      synthesis, and delivery to client apoproteins may be tightly controlled.

PMID- 21951715
TI  - Modification of Glasgow Coma Scale criteria for injured elders.
AB  - OBJECTIVES: An abnormal field Glasgow Coma Scale (GCS) score of <=13 has been
      used in our emergency medical services (EMS) system to prompt transport to a
      trauma center. For elders, Ohio has recently adopted a GCS of <=14 to prompt EMS
      transport to a trauma center, as older patients respond differently to trauma and
      may benefit from a different GCS threshold. This study sought to determine if a
      field GCS of 14 is an appropriate cutoff to initiate transport to a trauma center
      among injured elders. METHODS: This was a retrospective, observational statewide
      analysis of injured patients >=16 years old captured by the Ohio Trauma Registry
      from 2002 to 2007. Outcomes studied included mortality, traumatic brain injury
      (TBI), neurosurgical intervention, and endotracheal intubation (ETI). Multiple
      imputation was performed to account for missing data. Age-stratified sensitivity
      and specificity for proposed GCS cutoffs of 13 and 14 were calculated. A series
      of multivariate logistic regression models was then constructed using each
      outcome as a dependent variable. Independent variables included age, GCS score,
      sex, blood pressure, injury type, nontrauma center, race, ethnicity, and Injury
      Severity Score (ISS). Two separate analyses were performed. For each age group,
      odds ratios (ORs) of each outcome were calculated both for the decrease in GCS
      from 15 to 14 and for the decrease from 14 to 13. The group of elders with GCS 14
      was then compared to adults with GCS 13. RESULTS: A total of 52,412 study
      patients were identified. For a GCS cutoff of 13, sensitivity among elders for
      each outcome was >20% less than sensitivity for adults, and specificity was 5% to
      10% greater. Increasing the GCS cutoff for elders to 14 resulted in improved
      sensitivity for all outcomes (approximately 10%), with a decline in specificity
      to values near that of adults with GCS 13. In the multivariate models for elders,
      mortality increased with a decrease in GCS both from 15 to 14 (OR = 1.40, 95%
      confidence interval [CI] = 1.07 to 1.83) and from GCS 14 to 13 (OR = 2.34, 95% CI
      = 1.57 to 3.52). In adults, mortality did not increase with the drop from GCS 15
      to 14 (OR = 1.22, 95% CI = 0.88 to 1.71) or from GCS 14 to 13 (OR = 1.45, 95% CI
      = 0.91 to 2.30). When comparing elders with GCS 14 to adults with GCS 13, elders
      had greater odds of mortality (OR = 4.68, 95% CI = 2.90 to 7.54) and TBI (OR =
      1.84, 95% CI = 1.45 to 2.34). CONCLUSIONS: Changing the EMS trauma triage cutoff
      for elders from GCS 13 to GCS 14 results in improved sensitivity for clinically
      relevant outcomes. In injured elders, the decline in GCS from 15 to 14 is
      associated with increased mortality, a finding not observed in younger adults.
      Elders with GCS 14 have greater odds of mortality and TBI than adults with GCS
      13. These results support recent changes in EMS trauma triage guidelines for
      elders adopted in Ohio.

PMID- 21951716
TI  - Simulating natural selection in landscape genetics.
AB  - Linking landscape effects to key evolutionary processes through individual
      organism movement and natural selection is essential to provide a foundation for
      evolutionary landscape genetics. Of particular importance is determining how
      spatially-explicit, individual-based models differ from classic population
      genetics and evolutionary ecology models based on ideal panmictic populations in
      an allopatric setting in their predictions of population structure and frequency
      of fixation of adaptive alleles. We explore initial applications of a spatially
      explicit, individual-based evolutionary landscape genetics program that
      incorporates all factors--mutation, gene flow, genetic drift and selection--that
      affect the frequency of an allele in a population. We incorporate natural
      selection by imposing differential survival rates defined by local relative
      fitness values on a landscape. Selection coefficients thus can vary not only for
      genotypes, but also in space as functions of local environmental variability.
      This simulator enables coupling of gene flow (governed by resistance surfaces),
      with natural selection (governed by selection surfaces). We validate the
      individual-based simulations under Wright-Fisher assumptions. We show that under
      isolation-by-distance processes, there are deviations in the rate of change and
      equilibrium values of allele frequency. The program provides a valuable tool
      (cdpop v1.0; http://cel.dbs.umt.edu/software/CDPOP/) for the study of
      evolutionary landscape genetics that allows explicit evaluation of the
      interactions between gene flow and selection in complex landscapes.

PMID- 21951717
TI  - Assessment of high-sensitivity CRP as a marker of micro-inflammation in irritable
      bowel syndrome.
AB  - BACKGROUND: The diagnosis of irritable bowel syndrome (IBS) is symptom-based.
      Although considered a functional disease, accumulating evidence supports a low
      grade gut inflammation as an element of its pathophysiology. Thus, high
      sensitivity C-reactive protein (hs-CRP), a marker of micro inflammation, may be
      elevated in IBS. Our aim was to assess whether hs-CRP is higher in IBS patients
      compared to healthy controls (HC) and does it differ among the IBS clinical
      subgroups and correlate with disease severity. METHODS: A diagnostic case control
      study was conducted in two gastroenterology departments. Eighty-eight IBS
      patients who were recruited prospectively answered the Rome III diagnostic
      questionnaire. They all completed the Functional Bowel Disorder Severity Index
      (FBDSI), dietary, and general health questionnaires. All patients underwent blood
      sampling for hs-CRP levels. Each IBS patient was matched to four HC by age,
      gender, and BMI. Blood samples were obtained from the HC at a periodic health
      survey. KEY RESULTS: The mean hs-CRP level in the IBS group was significantly
      higher than in HC (1.17+/-1.26mg L(-1) vs 0.72+/-0.91mg L(-1) respectively,
      P=0.001). Hs-CRP levels were highest in patients with diarrhea-predominant IBS
      and in patients with greater disease severity. A cut-off value of 1.08mg L(-1)
      had a sensitivity of 60.2% and a specificity of 68% for differentiating IBS from
      HC. CONCLUSIONS & INFERENCES: Hs-CRP levels are higher in IBS patients than HC,
      but still in the normal laboratory range. This may reflect the low-grade gut
      inflammation believed to occur in IBS and support its existence.

PMID- 21951718
TI  - Using critical realism in nursing and health research: promise and challenges.

PMID- 21951719
TI  - Long-term outcomes following neoadjuvant chemoradiotherapy in patients with
      clinical T2N0 esophageal squamous cell carcinoma.
AB  - The optimal treatment for patients with local esophageal cancer (cT2N0 disease)
      has not yet been defined. We sought to determine whether neoadjuvant
      chemoradiotherapy (CRT) can improve prognosis compared with direct esophagectomy
      in this patient group. Between 1994 and 2005, patients with cT2N0 esophageal
      squamous cell carcinoma who underwent either neoadjuvant CRT or surgery as first
      line treatment were retrospectively reviewed. We collected information on their
      demographic characteristics, staging modality, clinical and pathological stages,
      perioperative course, and survival. The study endpoints included tumor
      recurrence, disease-specific survival (DSS), and overall survival rate. Of the 71
      eligible patients, 14 received an esophagectomy first, whereas the remaining 57
      received neoadjuvant CRT first. Despite the high pathological complete response
      (pCR) rate of 37% after neoadjuvant CRT, routine neoadjuvant CRT did not
      translate into better survival compared to direct surgery (5-year DSS: 39% vs.
      68%, P= 0.17). The dramatic survival difference between pCR and non-pCR patients
      (5-year DSS: 85% vs. 4%, P < 0.001) accounts for these unsatisfactory results. In
      our series, the administration of neoadjuvant CRT to patients with clinical stage
      T2N0 esophageal squamous cell carcinoma did not significantly improve outcomes
      compared with direct esophagectomy.

PMID- 21951720
TI  - Safety culture in the maternity units: a census survey using the Safety Attitudes
      Questionnaire.
AB  - BACKGROUND: Patient safety has been a priority for many societies and health care
      systems in the last decades. Identification of preventable risks and aversion of
      potentially unsafe situations and fatal complications in maternity units is life
      saving. The explicit need to focus on quality of care underpins the aim of the
      study to initially evaluate the safety culture and teamwork climate in the public
      Maternity Units of the 5 Regional Hospitals in Cyprus as measured by a validated
      safety attitudes tool. METHODS: Data were collected from 140 midwives working in
      the public sector all over Cyprus by the Greek Version of the Safety Attitudes
      Questionnaire-Labor version. RESULTS: One hundred and six (75.71%) registered
      midwives completed the questionnaire fully. The median of total work experience
      as a registered midwife was 3 years (IQR: 2-18.25); whereas the median of total
      working experience in the nursing and maternity units was 5 years (IQR: 2-21.75).
      Experienced midwives rated the following domains higher: team work, safety
      climate, job satisfaction and working conditions as opposed to the midwives with
      less experience. Additionally those with a longer working life in the current
      maternity units rated these domains higher: safety climate, job satisfaction and
      working conditions as opposed to the less experienced midwives. CONCLUSIONS: The
      high mean total score on team work and safety climate in the more experienced
      group of midwives is a predominant finding for the maternity units of Cyprus. In
      Cyprus where facilities are small in size and midwives know each other, share
      more responsibility towards patient safety. It could be suggested that younger
      midwives need more support and teamwork practice to enhance the safety and
      teamwork climate towards self-confidence.

PMID- 21951721
TI  - Prevalence and socio-demographic correlates for serious injury among adolescents
      participating in the Djibouti 2007 Global School-based Health Survey.
AB  - BACKGROUND: Mental health and injury are neglected public health issues
      especially in low-income nations. The objective of the study was to determine the
      prevalence and socio-demographic correlates for serious injury in the last 12
      months. FINDINGS: The study used data of the 2007 Djibouti Global School-based
      Health Survey. Logistic regression analysis was used to establish associations.
      Of the 1, 777 respondents, 61.1% (63.2% males and 57.8% females) reported having
      sustained serious injury (SSI). Compared to participants who were not bullied,
      those who reported being bullied 3-9 days per month were more likely to have
      sustained serious injury in the last 12 months (AOR = 1.27; 95% CI [1.06, 1.52]
      for 3-5 days of bullying victimization per month, and AOR = 3.19; 95% CI [2.28,
      4.47] for 6-9 days per month. Adolescents who were engaged in physical fighting
      were 47% (AOR = 1.47, 95% CI [1.40, 1.55] more likely to have sustained serious
      injury compared to those who were not engaged in the fighting. Meanwhile,
      adolescents who used substances (cigarettes, other forms of tobacco or drugs)
      were 30% (AOR = 1.30, 95% CI [1.19, 1.42]) more likely to have sustained serious
      injury compared to those who did not use substances. CONCLUSIONS: Serious injury
      is common among adolescents in Djibouti, and we suggest that health workers
      attending to injured adolescents explore the patients' psycho-social environment.
      Further, we suggest longitudinal studies where reduction of substance use and
      bullying may be assessed if they have an impact in reducing serious injury among
      adolescents.

PMID- 21951722
TI  - Competitive exclusion: phylogeography's 'elephant in the room'?
AB  - Phylogeographic and evolutionary research programmes have successfully elucidated
      compelling genetic signatures of earth history. Particularly influential
      achievements include the demonstration of postglacial recolonization patterns for
      high-latitude taxa and phylogenetic demonstration of the 'progression rule' along
      oceanic island chains such as Hawaii. While both of these major biogeographic
      patterns clearly rely on rapid dispersal over long distances, their
      phylogeographic detection also apparently relies on the competitive exclusion of
      secondary dispersers. Such exclusion could occur either between or within species
      and might reflect fitness differences between lineages or, alternatively, neutral
      demographic processes (e.g. 'high-density blocking'). Regardless, such spatial
      genetic patterns would be rapidly eroded were it not for the failure of
      subsequent dispersers to contribute genetically to newly colonized populations.
      In addition to its role in revealing colonization patterns, competitive exclusion
      may also explain the maintenance of historic phylogeographic disjunctions long
      after the original physical barriers to dispersal have ceased to exist.
      Additionally, some of the most persuasive evidence of competitive exclusion comes
      from studies of anthropogenic extinction, where surviving lineages have
      subsequently expanded their ranges, apparently benefitting from the demise of
      their prehistoric sisters. Broadly, these biogeographic paradigms are united by
      the 'disconnect' between dispersal and colonization success, the latter being
      heavily influenced by inter- and intraspecific competition. Despite its apparent
      importance, such exclusion (especially within species) has received virtually no
      attention in the phylogeographic literature. Future studies should aim to test
      directly for the role of competitive exclusion in constraining the biogeography
      of highly dispersive taxa.

PMID- 21951723
TI  - The Hsp90 chaperone machinery: conformational dynamics and regulation by co
      chaperones.
AB  - Hsp90 is a dimeric molecular chaperone required for the activation and
      stabilization of numerous client proteins many of which are involved in essential
      cellular processes like signal transduction pathways. This activation process is
      regulated by ATP-induced large conformational changes, co-chaperones and
      posttranslational modifications. For some co-chaperones, a detailed picture on
      their structures and functions exists, for others their contributions to the
      Hsp90 system is still unclear. Recent progress on the conformational dynamics of
      Hsp90 and how co-chaperones affect the Hsp90 chaperone cycle significantly
      increased our understanding of the gearings of this complex molecular machinery.
      This article is part of a Special Issue entitled: Heat Shock Protein 90 (Hsp90).

PMID- 21951726
TI  - Chronic disseminated discoid lupus erythematosus with linear lesions following
      Blaschko's lines on forearm and hand.

PMID- 21951724
TI  - Role of TRIPTYCHON in trichome patterning in Arabidopsis.
AB  - BACKGROUND: Trichome patterning in Arabidopsis thaliana is governed by three
      types of activators, R2R3MYB, bHLH and WD40 proteins, and six R3MYB inhibitors.
      Among the inhibitors TRIPTYCHON (TRY) seems to fulfill a special function. Its
      corresponding mutants produce trichome clusters whereas all other inhibitors are
      involved in trichome density regulation. RESULTS: To better understand the role
      of TRY in trichome patterning we analyzed its transcriptional regulation. A
      promoter analysis identified the relevant regulatory region for trichome
      patterning. This essential region contains a fragment required for a double
      negative feedback loop such that it mediates the repression of TRY/CPC auto
      repression. By transforming single cells of pTRY:GUS lines with p35S:GL1,
      p35S:GL3 and p35S:TTG1 in the presence or absence of p35S:TRY or p35S:CPC we
      demonstrate that TRY and CPC can suppress the TRY expression without the
      transcriptional down regulation of the activators. We further show by
      promoter/CDS swapping experiments for the R3MYB inhibitors TRY and CPC that the
      TRY protein has specific properties relevant in the context of both, cluster
      formation and trichome density. CONCLUSIONS: Our identification of a TRY promoter
      fragment mediating a double negative feedback loop reveals new insight in the
      regulatory network of the trichome patterning machinery. In addition we show that
      the auto-repression by TRY can occur without a transcriptional down regulation of
      the activators, suggesting that the differential complex formation model has a
      biological significance. Finally we show that the unique role of TRY among the
      inhibitors is a property of the TRY protein.

PMID- 21951725
TI  - MICAL-L1 is a tubular endosomal membrane hub that connects Rab35 and Arf6 with
      Rab8a.
AB  - Endocytosis is a conserved process across species in which cell surface receptors
      and lipids are internalized from the plasma membrane. Once internalized,
      receptors can either be degraded or be recycled back to the plasma membrane. A
      variety of small GTP-binding proteins regulate receptor recycling. Despite our
      familiarity with many of the key regulatory proteins involved in this process,
      our understanding of the mode by which these proteins co-operate and the
      sequential manner in which they function remains limited. In this study, we
      identify two GTP-binding proteins as interaction partners of the endocytic
      regulatory protein molecule interacting with casl-like protein 1 (MICAL)-L1.
      First, we demonstrate that Rab35 is a MICAL-L1-binding partner in vivo. Over
      expression of active Rab35 impairs the recruitment of MICAL-L1 to tubular
      recycling endosomes, whereas Rab35 depletion promotes enhanced MICAL-L1
      localization to these structures. Moreover, we demonstrate that Arf6 forms a
      complex with MICAL-L1 and plays a role in its recruitment to tubular endosomes.
      Overall, our data suggest a model in which Rab35 is a critical upstream regulator
      of MICAL-L1 and Arf6, while both MICAL-L1 and Arf6 regulate Rab8a function.

PMID- 21951727
TI  - Sexual behavior of HIV-positive women in Cameroon.
AB  - This study aimed at describing the sexual behavior of HIV-positive women in
      Cameroon. In a cross-sectional study, 282 HIV-infected women were enrolled in 3
      HIV-treatment clinics in Cameroon. Of the 282 participants, 257 had been
      diagnosed with HIV for more than 6 months. Approximately half (46.8%) of these
      257 women reported no sex partners in the 6 months before the study; 42.9% had 1
      partner; and 1.5% had more than 1 partner. There was a significant decrease in
      the number of partners, new partners, and an increase in condom use with these
      partners following HIV diagnosis (P value < .05). However, more than half (55.2%)
      of the sexually active participants reported inconsistent or no condom use during
      sexual intercourse. Although HIV-positive women tend to adopt less risky behavior
      after HIV diagnosis, a substantial proportion of sexually active ones still have
      risky behaviors. Reinforcing risk reduction programs for these women is
      imperative.

PMID- 21951729
TI  - The false diagnosis of venous leak: prevalence and predictors--a comment.

PMID- 21951728
TI  - Poorer ART outcomes with increasing age at a large public sector HIV clinic in
      Johannesburg, South Africa.
AB  - BACKGROUND: As the current HIV-positive population ages, the absolute number of
      patients >50 years on treatment is increasing. METHODS: We analyze the
      differences in treatment outcomes by age category (18-29, 30-39, 40-49, 50-59,
      and >= 60) among 9139 HIV-positive adults initiating ART in South Africa.
      RESULTS: The adjusted hazard ratios (HRs) for all-cause mortality increased with
      increasing age, with the strongest association in the first 12 months of follow
      up among patients 50 to 59 years (HR 1.67; 95% confidence interval [CI]: 1.24
      2.23) versus those <30 years. However, patients 50 to 59 years were less likely
      to be lost during 24 months on antiretroviral therapy ([ART] HR 0.75; 95% CI:
      0.59-0.94) versus patients <30 years. By 6 and 12 months on treatment, older
      patients were less likely to increase their CD4 count by >= 50 cells/mm(3).
      CONCLUSION: Although older patients are at higher risk of mortality and have
      poorer immunological responses than their younger counterparts, they are more
      likely to adhere to care and treatment in the first 24 months on ART.

PMID- 21951730
TI  - Who cares for family caregivers of patients with cancer?

PMID- 21951731
TI  - Accessing implanted ports remains controversial.

PMID- 21951732
TI  - Calculating nutrition needs for a patient with head and neck cancer.
AB  - Patients with head and neck cancer often have distinct nutrition needs. The
      unique set of side effects of the disease process and treatment cause the patient
      to develop nutritional challenges. The challenges are complex to manage, often
      requiring supplemental feedings. Proper calculation of protein and caloric intake
      is necessary to meet the increased needs. Taking treatment and activity levels
      into account also is necessary when calculating nutrition requirements. Fluid
      balance can be delicate and requires attention, too. The dietitian determines the
      fluid needs of patients, using one of several calculations, and need is based on
      the patients' laboratory work and overall hydration status, which can be affected
      by inadequate fluid intake, diarrhea, and vomiting.

PMID- 21951733
TI  - Advancing the scope of nursing practice: hepatic arterial catheter removal.
AB  - A delay in hepatic artery infusion catheter removal may prolong patient
      discomfort and lead to additional complications. As a result, this article
      evaluated the effectiveness of shifting the responsibility of catheter removal
      from advanced practice or medical staff to nurses. Overall, patients were
      satisfied, felt comfortable, and experienced minimal pain irrespective of whether
      their catheter was removed by a nurse, physician, or advanced practice staff.
      Nurses also were satisfied and felt they had enhanced their ability to provide
      quality patient care.

PMID- 21951734
TI  - Dosing done right: a review of common chemotherapy calculations.
AB  - The potential for medication error is great with chemotherapy agents because of
      their high toxicity profile, small therapeutic index, and numerous dose-limiting
      adverse effects. The oncology team involved with chemotherapy treatment planning
      and administration assumes an active role in preventing such events by obtaining
      and maintaining competency in dose calculations, having knowledge of dose
      limiting toxicities, appropriate ordering of drug regimens, and participation in
      safety verification processes. This article will provide a review of evidence
      based formulas and their rationale for use in dosing chemotherapy, case scenarios
      with practice calculations, and recommendations for safe verification of
      chemotherapy drug order accuracy.

PMID- 21951735
TI  - Putting evidence into practice.
AB  - Radiation dermatitis, or radiodermatitis, is a significant symptom caused by
      radiation therapy for the treatment of cancerous and noncancerous conditions.
      Radiodermatitis can negatively affect patients' physical functioning and quality
      of life. The Oncology Nursing Society coordinated a Putting Evidence Into
      Practice (PEP) project team to develop a PEP resource summarizing current
      evidence for the management of patients with radiodermatitis. Oncology nurses
      play an important role in educating, assessing, and monitoring patients for this
      symptom. Many common nursing interventions for radiodermatitis are based on
      tradition or opinion and have not been researched thoroughly. In addition,
      evidence to support some current interventions in practice is lacking. This
      article presents information concerning radiodermatitis, summarizes the evidence
      based review for its prevention and management, and identifies gaps in the
      literature, as well as opportunities for research, education, and practice.

PMID- 21951736
TI  - Preemptive management of dermatologic toxicities associated with epidermal growth
      factor receptor inhibitors.
AB  - Epidermal growth factor receptor inhibitors (EGFRIs) are a treatment option for
      patients diagnosed with advanced-stage gastrointestinal, lung, and head and neck
      cancers. The most prevalent complications associated with EGFRIs are dermatologic
      toxicities, which may result in either disruption or discontinuation of treatment
      and adversely affect patients' quality of life. Nurses play a vital role in
      educating patients about EGFRI-related dermatologic toxicities; therefore, nurses
      must continue to educate themselves on the various aspects of EGFRI treatment. An
      overview of the EGF signaling pathway is provided, and dermatologic toxicities
      associated with EGFRI treatment are described. A review of several studies
      evaluating reactive skin treatment regimens also are discussed. Nurses play a
      critical role in providing patient support. Informing patients about potential
      EGFRI-related symptoms and dermatologic toxicities will help prepare patients for
      their course of treatment. In addition, nurses should provide patients with a
      variety of coping strategies to help manage dermatologic toxicities that will
      assist in enhancing patients' adherence to EGFRI treatment.

PMID- 21951737
TI  - Nursing considerations with pazopanib therapy: focus on metastatic renal cell
      carcinoma.
AB  - The rapid evolution of targeted therapies has had a dramatic impact on multiple
      domains in oncology, particularly metastatic renal cell carcinoma (RCC). Four
      agents antagonizing vascular endothelial growth factor-mediated signaling have
      been approved for the treatment of metastatic RCC, including the monoclonal
      antibody bevacizumab and the small molecular inhibitors sunitinib, sorafenib, and
      pazopanib. Pazopanib was approved in 2009 for this disease on the basis of a
      phase III clinical trial demonstrating a superior progression-free survival
      compared to placebo in 435 patients with either treatment-naive or cytokine
      refractory disease. The trial offered insight related to the toxicity profile
      associated with this agent. The most common clinical adverse events are diarrhea,
      hypertension, nausea, anorexia, and vomiting. With respect to laboratory adverse
      events, hepatotoxicity represents a specific concern with pazopanib. Oncology
      nurses play a critical role in counseling patients regarding the toxicity profile
      and management of adverse events in pazopanib treatment.

PMID- 21951739
TI  - Nurses as patient advocates in oncology care: activities based on literature.
AB  - This article will explore oncology nurses' patient advocacy activities and
      compare those activities with patient advocacy activities defined in an earlier
      study by the authors. Data were collected from 42 English-language peer-reviewed
      articles published from 2000-2010. Search terms used included cancer care and
      advocacy and oncology nursing and advocacy. According to the findings of the
      reviewed articles, oncology nurses promote the interests of their patients by
      analyzing patients' psychosocial and physical distress and care plans,
      particularly at the beginning of the illness trajectory. Oncology nurses also are
      instructed in the literature to educate patients about cancer management prior to
      the first treatment and during cancer management to promote informed consent, but
      not to analyze patients' information or self-determination preferences. Oncology
      nurses do, however, advocate for their patients by presenting and raising
      awareness of patients' needs and preferences in regard to the healthcare system.
      To some degree, this advocacy can be seen as responding to patients' care and
      self-determination preferences. Oncology nurses' patient advocacy activities are
      similar to advocacy activities defined in the context of procedural pain care but
      are more focused on the beginning of the illness trajectory. However, care and
      self-determination needs, information needs, and advocacy needs of patients with
      cancer vary during the illness trajectory. Those needs should be analyzed and
      responded to systematically.

PMID- 21951738
TI  - The use of healing touch in integrative oncology.
AB  - The use of complementary therapies by patients with cancer has become
      increasingly prevalent; as a result, oncology nurses find themselves needing to
      understand those therapies and the evidence-based support for their use. This
      article describes the integrative use of the biofield therapy healing touch in
      conjunction with the chemoradiation received by patients with cervical cancer
      (stages IB1 to IVA) as reported in a 2010 research study. Findings indicated
      effects on the immune response and depression in healing touch recipients
      compared to patients receiving relaxation or standard care. Specifically, healing
      touch recipients demonstrated a minimal decrease in natural killer cell
      cytotoxicity over the course of treatment, whereas the cytotoxicity of patients
      receiving relaxation therapy and standard care declined sharply during radiation.
      Healing touch recipients also showed decreases in depressed mood compared to
      relaxation therapy and standard care recipients. The findings suggest that
      appropriate integration of complementary modalities into oncology care can
      enhance the impact of conventional care by putting patients in the best condition
      to use their innate healing resources.

PMID- 21951740
TI  - Practical management of imatinib in gastrointestinal stromal tumors.
AB  - Gastrointestinal stromal tumors (GISTs) have an incidence of 7-15 occurrences per
      million people. Tyrosine kinase inhibitors (TKIs) have significantly improved
      clinical outcomes as part of multidisciplinary disease management. The authors
      will review developments in the management of GISTs, including diagnosis, risk
      stratification, prognosis, and treatment with imatinib. Imatinib is recommended
      for postsurgical adjuvant therapy and, where appropriate, neoadjuvant therapy.
      Clinical practice guidelines recommend first-line imatinib for metastatic and
      unresectable GISTs based on trials showing efficacy at the standard dose (400 mg
      per day) and at higher doses of 600-800 mg per day. Oncology nurses play a key
      role in patient management through (a) patient education about GISTs and their
      treatment including the use of imatinib, (b) timely scheduling of radiologic
      follow-up to assess treatment response, (c) monitoring treatment adherence, (d)
      helping to sustain imatinib dose intensity by monitoring toxicities and drug
      interactions and by counseling patients to prevent treatment interruptions, and
      (e) collaborating with the multidisciplinary medical team to pursue imatinib dose
      escalation or other treatment options if patients have primary or acquired
      mutation-based resistance to imatinib.

PMID- 21951741
TI  - Current practices in advance care planning: implications for oncology nurses.
AB  - Discussions regarding advance care planning (ACP) among patients with cancer and
      their physicians largely are not happening. Many patients with cancer, even those
      at the end of life (EOL), have not established an advance directive (AD). Lack of
      EOL discussions and receipt of aggressive care at the EOL have resulted in poor
      health outcomes for patients. In contrast, EOL discussions and early palliative
      care resulted in positive health outcomes for patients with cancer. The purpose
      of this review is to determine the current practices of ACP between healthcare
      providers and their patients in the United States and the use of ADs,
      particularly among patients with cancer. In addition, the authors offer
      recommendations for nurses and nurse practitioners on how to assist patients in
      ACP and the establishment of ADs. Research studies from peer-reviewed journals
      and reports from professional associations and agencies in the United States,
      published from 2002-2011, were reviewed and summarized. Nurses and nurse
      practitioners are in key positions to help patients with ACP and establishing
      ADs. Education and training for nurses and nurse practitioners regarding ACP
      needs to continue, and more research on the nurse practitioner's role in ACP
      should be conducted.

PMID- 21951742
TI  - The relationship between vitamin D and cancer.
AB  - Vitamin D, a fat-soluble vitamin naturally present in very few foods, is
      synthesized when ultraviolet rays from sunlight contact the skin. Research
      suggests that vitamin D insufficiency may result from lack of exposure to
      sunlight and ultraviolet-B radiation. Individuals from geographic areas of high
      latitude and low sunlight exposure may be at increased risk for vitamin D
      deficiency. Emerging evidence supports the protective role of vitamin D in the
      prevention of several cancers, including breast, colon, and prostate.

PMID- 21951743
TI  - Hypertrophic osteoarthropathy as a clinical manifestation of lung cancer.
AB  - Hypertrophic osteoarthropathy is a paraneoplastic syndrome most often found in
      non-small cell lung cancer. Diagnosis is confirmed by the presence of clubbing on
      physical examination and periostitis on bone scintigram, and the syndrome
      generally resolves with treatment of the underlying malignancy. This article
      presents a case study and describes symptom management options, including
      nonsteroidal anti-inflammatory agents, octreotide, and bisphosphonates.

PMID- 21951744
TI  - Evolution of an international collaboration: a unique experience across borders.
AB  - An international collaboration to support and mentor palliative care nurses was
      developed between two educational institutions in the New England region of the
      United States and the Hospice Casa Sperantei in Brasov, Romania. Through
      teleconferences, onsite visits, research, and shared publications, the
      collaboration continues to be a dynamic experience for the partners and students.
      The seven-year relationship has affected the Romanian nursing team by providing
      professional education and support, as well as validation of clinical practice.

PMID- 21951745
TI  - Fighting ovarian cancer one step at a time.

PMID- 21951746
TI  - Exercise interventions for upper-limb dysfunction caused by breast cancer
      treatment.

PMID- 21951748
TI  - Immunotherapy for advanced melanoma.
AB  - The anticytotoxic T-lymphocyte antigen-4 (CTLA-4) monoclonal antibody ipilimumab
      was approved recently by the U.S. Food and Drug Administration for the treatment
      of patients with unresectable or metastatic melanoma. Anti-CTLA-4 treatment
      yields tumor responses or stable disease that may last months or years. Antitumor
      responses can occur within the first few weeks or even months after initiation of
      treatment, even as the disease appears to be progressing or new lesions are
      detected. Most side effects are immune related, consistent with the immune-based
      mechanism of action, and generally manageable with supportive measures and
      steroids. With anti-CTLA-4 therapy, patient response differs (both clinically and
      psychologically) to that generally observed with chemotherapy or other agents
      used to treat advanced cancer. Patients and caregivers require education about
      the likely patterns of response to treatment to help them understand why
      beneficial clinical outcomes may require weeks or months to occur and why
      continued treatment may be advisable, even when the disease may appear to be
      progressing. At the author's institution, the staff have noted that patients also
      need increased psychological support as a result of these clinical features and
      decisions. Patients and caregivers require instruction on recognition of
      potential side effects, the importance of reporting them in a timely manner, and
      their management.

PMID- 21951749
TI  - Effects of oncology clinical nurse specialists' interventions on nursing
      sensitive outcomes in South Korea.
AB  - This study compared outcomes, including pain, fatigue, anxiety, satisfaction,
      health-related quality of life (HRQOL), ease of access, and unexpected emergency
      room (ER) visits, for patients with cancer in South Korea who were cared for by
      an oncology clinical nurse specialist (CNS) with patients with cancer who were
      not. Self-report questionnaires and semistructured interviews were used to
      appraise the performance of oncology CNSs, and medical characteristics were
      obtained through chart review. CNS interventions were found to diminish some
      intensity scores of pain and fatigue, and to increase HRQOL, satisfaction with
      trustworthiness, and ease of access. No significant effects were observed on
      anxiety or unexpected ER visits. The current study provides evidence that
      oncology CNSs are effective in South Korea, which will be the basis of validating
      the implementation and expansion of policy for oncology nursing.

PMID- 21951750
TI  - Colorectal cancer family history assessment.
AB  - This article describes family history assessment for colorectal cancer in three
      outpatient gastroenterology units and examines gastroenterology unit nurses'
      knowledge and attitudes about family history assessments. Eighty-eight
      colonoscopy records were surveyed, and 16 RNs were interviewed. The medical
      record documentation was surveyed using a researcher-developed tool to identify
      type of cancer, age at disease onset, family relationship, and number of family
      members with cancer. Gastroenterology unit nurses were interviewed to assess
      knowledge and attitudes about family history assessment regarding colorectal
      cancer. Findings indicate that limited family history documentation was present
      in the medical record and that important age-at-disease-onset information was
      missing in 95% of patients with a family history of colorectal cancer and in 85%
      of patients with a family history of Lynch syndrome-associated cancers. No
      documentation was found in any charts about the number of affected relatives
      within the same family. Inconsistencies in family history documentation within
      the same medical record were noted, and family history information was found in
      multiple chart forms. Gastroenterology nurses rated family history as very
      important but gave a lower rating to personal knowledge about and resources for
      family history assessment.

PMID- 21951751
TI  - Managing stomatitis in patients treated with Mammalian target of rapamycin
      inhibitors.
AB  - Mammalian target of rapamycin (mTOR) inhibitors are a class of targeted cancer
      therapeutic agents with clinical benefit for multiple tumor types. Oral
      ulcerations are a common side effect of mTOR inhibitors; however, the clinical
      findings resemble aphthous stomatitis rather than the mucositis seen with
      chemotherapy. Consequently, the appearance of aphthous-like oral ulcerations has
      been referred to as mTOR inhibitor-associated stomatitis (mIAS). The severity of
      mIAS can be minimized by following common preventive steps and initiating
      treatment at the first sign of mouth discomfort, thereby reducing the likelihood
      of treatment discontinuation. mIAS can be managed through prophylactic measures,
      such as patient education in oral hygiene and avoidance of triggers. Patients who
      develop mIAS may be treated topically using rinses or other local therapies,
      including corticosteroids. In severe cases, dose modifications may be required.
      Oncology nurses have an important role in the management of patients with cancer
      and are well positioned to offer strategies for minimizing the occurrence and
      impact of mIAS.

PMID- 21951752
TI  - An examination of patient-identified goals for treatment in a first-episode
      programme in Chennai, India.
AB  - AIM: Our objective was to describe the goals identified by patients upon entering
      a specialized programme for treatment of first-episode psychosis (FEP) in
      Chennai, India. METHODS: 68 patients with FEP completed the Goal Attainment
      section of the Wisconsin Quality of Life-Client Questionnaire upon entry into
      treatment. Patients were asked to identify a maximum of three treatment goals and
      rate each identified goal on its importance and the extent of its achievement.
      RESULTS: In the order of frequency of endorsement, the primary goals identified
      pertained to work, family/interpersonal relationships, education, symptom relief
      and psychological recovery, living condition, religion, finances, and household
      responsibilities. All patients identified at least one goal, 41 patients
      identified two goals, and 11 patients identified three goals. CONCLUSION:
      Individuals with FEP in India present with a range of realistic and reasonable
      goals. Findings have implications for improving early intervention services in
      India by targeting patient-identified goals.

PMID- 21951753
TI  - Predictors of duloxetine versus other treatments among veterans with diabetic
      peripheral neuropathic pain: a retrospective study.
AB  - OBJECTIVE: This study used medical and pharmacy records from the Veterans Affairs
      (VA) health system to explore the predictors of duloxetine versus other
      treatments for patients with diabetic peripheral neuropathic pain (DPNP).
      METHODS: The electronic medical and pharmacy records from January 2004 to
      December 2008 were requested from the Veterans Integrated Service Network 16 data
      warehouse. All select patients received either duloxetine or other treatments
      [tricyclic antidepressants (TCAs), venlafaxine, gabapentin, and pregabalin] over
      the study period, with the first dispense date of the index agent as the index
      date. All patients must have 1(+) prior DPNP diagnosis (ICD-9-CM: 250.6x or
      357.2), but no diagnoses of prior depression (ICD-9-CM: 296.2, 296.3, 300.4,
      309.1, or 311.0), fibromyalgia (ICD-9-CM: 729.1), or neuralgia (ICD-9-CM: 729.2).
      Logistic regression was used to examine the predictors of receiving duloxetine
      versus other treatments, controlling for demographics, comorbidities, prior pain
      level, prior use of other medications, and opioid use. RESULTS: The analytical
      sample included 2,694 patients (duloxetine cohort, n = 216; other-treatment
      cohort, n = 2,478). Prior uses of gabapentin (odds ratio [OR] = 13.66, 95%
      confidence interval [CI]: 9.70-19.24), TCAs (OR = 5.40, 95% CI: 3.73-7.82), or
      venlafaxine (OR = 3.67, 95% CI: 1.67-8.06) were strong predictors of duloxetine.
      Other comorbidities associated with duloxetine were anxiety (OR= 2.08, 95% CI:
      1.40-3.08), cerebrovascular disease (OR = 1.44, 95% CI: 1.01-2.07), and substance
      abuse (OR = 2.11, 95% CI: 1.10-4.03). Prior opioid users were 1.47 (95% CI: 1.02
      2.12) times as likely to receive duloxetine as those without prior opioid use.
      Patients with self-reported severe pain were 1.66 (95% CI: 1.11-2.50) times as
      likely to receive duloxetine as those with no pain reported. CONCLUSION: DPNP
      patients in the VA healthcare system with prior other treatment use, select
      comorbid conditions, prior substance abuse, prior opioid use, and higher pain
      level were more likely to receive duloxetine.

PMID- 21951754
TI  - Commonly used antihypertensives and lower urinary tract symptoms: results from
      the Boston Area Community Health (BACH) Survey.
AB  - Study Type - Prevalence (inception cohort) Level of Evidence 1b What's known on
      the subject? and What does the study add? Certain antihypertensives, particularly
      diuretics and calcium channel blockers, are known to be associated with increased
      risk of LUTS including nocturia, but little is known about gender-specific
      effects. This is the first epidemiological study, to our knowledge, to compare
      the prevalence of several urological symptoms (storage, voiding and nocturia)
      among male and female users of a wide variety of common antihypertensives using a
      community-based sample. OBJECTIVE: To examine differences in the prevalence of
      lower urinary tract symptom (LUTS) among users of five common AHT classes
      compared with non-users, adjusted for LUTS risk factors in a large,
      representative sample. SUBJECTS AND METHODS: Data were from the Boston Area
      Community Health Survey, a population-based study of community-dwelling male and
      female (30-79 years) residents of Boston, MA, USA for whom prescription drug
      information was collected between 2002 and 2005. The urological symptoms of
      storage, voiding, and nocturia were assessed using interviewer-administered
      questionnaires and the American Urological Association Symptom Index. This
      analysis was conducted among 1865 participants with an AHT indication.
      Associations of angiotensin-converting enzyme inhibitors, beta blockers, calcium
      channel blockers (CCBs) and loop and thiazide diuretics with the three groups of
      LUTS were estimated using odds ratios (ORs) and 95% confidence intervals (CIs)
      from multivariate logistic regression (referent group: untreated hypertension).
      Overlap in use was accounted for using monotherapy and combination therapy
      exposure categories. RESULTS: Among women, monotherapy with CCBs was associated
      with increased prevalence of nocturia (OR = 2.65, 95% CI: 1.04-6.74) and voiding
      symptoms (OR = 3.84, 95% CI: 1.24-11.87); these results were confined to women
      aged <55 years. Among men of all ages, positive associations were observed for
      thiazides and voiding symptoms (monotherapy OR = 2.90, 95% CI: 1.17-7.19), and
      loop diuretics and nocturia (combination therapy OR = 2.55, 95% CI: 1.26-5.14).
      CONCLUSION: Results are consistent with the hypothesis that certain AHTs may
      aggravate LUTS. The presence of new or worsening LUTS among AHT users suggests
      medications should be reviewed and a change in AHT class considered.

PMID- 21951755
TI  - Potential factors that can be used to differentiate between interstitial
      cystitis/painful bladder syndrome and bladder oversensitivity in women.
AB  - AIM: There is considerable overlap between symptoms of interstitial
      cystitis/painful bladder syndrome (IC/PBS) and bladder oversensitivity, thereby
      making it difficult to differentiate between the two based on symptoms alone. We
      investigated factors that could potentially be used to differentiate between
      IC/PBS and bladder oversensitivity in women. MATERIALS AND METHODS: Video
      urodynamic study (VUDS) results in women with lower urinary tract symptoms (LUTS)
      were retrospectively analysed. Patients classified as having increased bladder
      sensation (IBS) were selected for analysis. A potassium chloride (KCl) test was
      performed and pain or urgency elicited was considered positive response.
      Cystoscopic hydrodistention demonstrating glomerulation was considered diagnosis
      of IC/PBS; otherwise bladder oversensitivity was diagnosed. LUTS, urodynamic
      variables and results of the KCl test were used to predict IC/PBS in these women.
      RESULTS: A total of 405 women with IBS and 272 symptomatic controls with normal
      VUDS findings were included. Among 227 IBS patients undergoing KCl test, a
      positive result was found in 190 and a negative test result was found in 37.
      Characteristic glomerulation was noted in 170 patients, including 165 with a
      positive and five with a negative KCl test. We found that storage symptoms and
      pain had a positive predictive value of 45.3% for IC/PBS. When a CBC <= 350 ml
      was added the positive predictive value was 65% for IC/PBS. A combination of
      storage symptoms, a CBC <= 350 ml, a positive KCl test result with an increase of
      >= 2 on the visual analogue pain scale (VAS) provided 100% predictive of IC/PBS.
      CONCLUSION: A diagnosis of IC/PBS can be made without cystoscopic hydrodistention
      in women with increased bladder sensation, having storage symptoms, a CBC <= 350
      ml, a positive KCl test result and a VAS score >= 2.

PMID- 21951756
TI  - Funding grant proposals for scientific research: retrospective analysis of scores
      by members of grant review panel.
AB  - OBJECTIVE: To quantify randomness and cost when choosing health and medical
      research projects for funding. DESIGN: Retrospective analysis. SETTING: Grant
      review panels of the National Health and Medical Research Council of Australia.
      PARTICIPANTS: Panel members' scores for grant proposals submitted in 2009. MAIN
      OUTCOME MEASURES: The proportion of grant proposals that were always, sometimes,
      and never funded after accounting for random variability arising from differences
      in panel members' scores, and the cost effectiveness of different size assessment
      panels. RESULTS: 59% of 620 funded grants were sometimes not funded when random
      variability was taken into account. Only 9% (n = 255) of grant proposals were
      always funded, 61% (n = 1662) never funded, and 29% (n=788) sometimes funded. The
      extra cost per grant effectively funded from the most effective system was
      $A18,541 (L11,848; ?13,482; $19,343). CONCLUSIONS: Allocating funding for
      scientific research in health and medicine is costly and somewhat random. There
      are many useful research questions to be addressed that could improve current
      processes.

PMID- 21951757
TI  - Comparing bivalent and quadrivalent HPV vaccines.

PMID- 21951758
TI  - Comparing bivalent and quadrivalent human papillomavirus vaccines: economic
      evaluation based on transmission model.
AB  - OBJECTIVES: To compare the effect and cost effectiveness of bivalent and
      quadrivalent human papillomavirus (HPV) vaccination, taking into account
      differences in licensure indications, protection against non-vaccine type
      disease, protection against disease related to HPV types 6 and 11, and reported
      long term immunogenicity. DESIGN: A model of HPV transmission and disease
      previously used to inform UK vaccination policy, updated with recent evidence and
      expanded to include scenarios where the two vaccines differ in duration of
      protection, cross protection, and end points prevented. SETTING: United Kingdom.
      Population Males and females aged 12-75 years. MAIN OUTCOME MEASURE: Incremental
      cost effectiveness ratios for both vaccines and additional cost per dose for the
      quadrivalent vaccine to be equally cost effective as the bivalent vaccine.
      RESULTS: The bivalent vaccine needs to be cheaper than the quadrivalent vaccine
      to be equally cost effective, mainly because of its lack of protection against
      anogenital warts. The price difference per dose ranges from a median of L19
      (interquartile range L12-L27) to L35 (L27-L44) across scenarios about vaccine
      duration, cross protection, and end points prevented (assuming one quality
      adjusted life year (QALY) is valued at L30,000 and both vaccines can prevent all
      types of HPV related cancers). CONCLUSIONS: The quadrivalent vaccine may have an
      advantage over the bivalent vaccine in reducing healthcare costs and QALYs lost.
      The bivalent vaccine may have an advantage in preventing death due to cancer.
      However, considerable uncertainty remains about the differential benefit of the
      two vaccines.

PMID- 21951760
TI  - Theoretical analysis of the effect of positioning on hemodynamic stability during
      pregnancy.
AB  - OBJECTIVES: A left lateral tilt of 15 degrees  has been advocated during trauma
      resuscitation of near-term pregnant patients to avoid the potential for
      hemodynamic compromise caused by aortocaval compression in the supine position.
      This recommendation is supported by limited objective evidence, and an
      experimental determination of the optimal tilt required would be very difficult
      to accomplish logistically. A derivation of the Guyton/Coleman/Summers computer
      model of cardiovascular physiology was used to analyze the theoretically expected
      hemodynamic responses to varying degrees of lateral tilt for a normal pregnancy
      and during a simulated hemorrhagic shock. METHODS: Computer simulation studies
      were used to predict the degree of left lateral tilt required to restore
      hemodynamic normalcy during the final 20 weeks of gestation. The analytic
      procedure involved recreating the clinical conditions for a virtual subject
      through a simulated reenactment of the clinical transfer of a pregnant patient
      from a lateral to a supine positioning. An analysis of model validity in the
      context of this particular clinical condition found the model predictions to be
      within 5% to 12% of experimental results. RESULTS: During the simulated lateral
      to supine position transfer, the virtual patient with Class I hemorrhage had a 7%
      greater fall in cardiac output and a 17% greater fall in mean arterial pressure
      (MAP) than the corresponding nonhemorrhagic patient. The model suggests that 15
      degrees  of tilt will result in hemodynamic normalization only up to 26 weeks of
      gestation. In addition, 13% greater tilt is required to achieve hemodynamic
      normalcy in the hemorrhaged term pregnant patient. CONCLUSIONS: Current trauma
      guidelines suggest that the pregnant trauma patient be placed in a 15 degrees 
      left lateral tilt position to prevent aortocaval compression. A computer
      simulation study suggests that this tilt may be inadequate to offload the vena
      cava and normalize the circulation.

PMID- 21951759
TI  - Semantic mappings and locality of nursing diagnostic concepts in UMLS.
AB  - One solution for enhancing the interoperability between nursing information
      systems, given the availability of multiple nursing terminologies, is to cross
      map existing nursing concepts. The Unified Medical Language System (UMLS)
      developed and distributed by the National Library of Medicine (NLM) is a
      knowledge resource containing cross-mappings of various terminologies in a
      unified framework. While the knowledge resource has been available for the last
      two decades, little research on the representation of nursing terminologies in
      UMLS has been conducted. As a first step, UMLS semantic mappings and concept
      locality were examined for nursing diagnostic concepts or problems selected from
      three terminologies (i.e., CCC, ICNP, and NANDA-I) along with corresponding
      SNOMED CT concepts. The evaluation of UMLS semantic mappings was conducted by
      measuring the proportion of concordance between UMLS and human expert mappings.
      The semantic locality of nursing diagnostic concepts was assessed by examining
      the associations of select concepts and the placement of the nursing concepts on
      the Semantic Network and Group. The study found that the UMLS mappings of CCC and
      NANDA-I concepts to SNOMED CT were highly concordant to expert mappings. The
      level of concordance in mappings of ICNP to SNOMED CT, CCC and NANDA-I within
      UMLS was relatively low, indicating the need for further research and
      development. Likewise, the semantic locality of ICNP concepts could be further
      improved. Various stakeholders need to collaborate to enhance the NLM knowledge
      resource and the interoperability of nursing data within the discipline as well
      as across health-related disciplines.

PMID- 21951761
TI  - Dot Bennett.

PMID- 21951763
TI  - Differentiating diabetic foot ulcers that are unlikely to heal by 12 weeks
      following achieving 50% percent area reduction at 4 weeks.
AB  - This retrospective analysis included intent-to-treat control patient data from
      two published, randomised, diabetic foot ulcer (DFU) trials in an effort to
      differentiate ulcers that are unlikely to heal by 12 weeks despite early healing
      progress [>=50% percent area reduction (PAR) at 4 weeks]. Predicted and actual
      wound area trajectories in DFUs that achieved early healing progress were
      analysed from weeks 5 to 12 and compared for ulcers that did and did not heal at
      12 weeks. In 120 patients who achieved >=50% PAR by week 4, 62 (52%) failed to
      heal by 12 weeks. Deviations from the predicted healing course were evident by 6
      weeks for non healing ulcers. A 2-week delay in healing significantly lowered
      healing rates (P = 0.001). For DFUs with >=50% PAR at 4 weeks, those achieving
      >=90% versus <90% PAR at 8 weeks had a 2.7-fold higher healing rate at 12 weeks
      (P = 0.001). A PAR of <90% at 8 weeks provided a negative predictive value for
      DFU healing at 12 weeks of 82%. For ulcers that fail to progress or worsen from
      weeks 4 to 6, and those that fail to achieve 90% PAR at 8 weeks, reevaluation of
      the wound and its treatment is recommended.

PMID- 21951762
TI  - Drosophila insulin and target of rapamycin (TOR) pathways regulate GSK3 beta
      activity to control Myc stability and determine Myc expression in vivo.
AB  - BACKGROUND: Genetic studies in Drosophila melanogaster reveal an important role
      for Myc in controlling growth. Similar studies have also shown how components of
      the insulin and target of rapamycin (TOR) pathways are key regulators of growth.
      Despite a few suggestions that Myc transcriptional activity lies downstream of
      these pathways, a molecular mechanism linking these signaling pathways to Myc has
      not been clearly described. Using biochemical and genetic approaches we tried to
      identify novel mechanisms that control Myc activity upon activation of insulin
      and TOR signaling pathways. RESULTS: Our biochemical studies show that insulin
      induces Myc protein accumulation in Drosophila S2 cells, which correlates with a
      decrease in the activity of glycogen synthase kinase 3-beta (GSK3beta ) a kinase
      that is responsible for Myc protein degradation. Induction of Myc by insulin is
      inhibited by the presence of the TOR inhibitor rapamycin, suggesting that insulin
      induced Myc protein accumulation depends on the activation of TOR complex 1.
      Treatment with amino acids that directly activate the TOR pathway results in Myc
      protein accumulation, which also depends on the ability of S6K kinase to inhibit
      GSK3beta activity. Myc upregulation by insulin and TOR pathways is a mechanism
      conserved in cells from the wing imaginal disc, where expression of Dp110 and
      Rheb also induces Myc protein accumulation, while inhibition of insulin and TOR
      pathways result in the opposite effect. Our functional analysis, aimed at
      quantifying the relative contribution of Myc to ommatidial growth downstream of
      insulin and TOR pathways, revealed that Myc activity is necessary to sustain the
      proliferation of cells from the ommatidia upon Dp110 expression, while its
      contribution downstream of TOR is significant to control the size of the
      ommatidia. CONCLUSIONS: Our study presents novel evidence that Myc activity acts
      downstream of insulin and TOR pathways to control growth in Drosophila. At the
      biochemical level we found that both these pathways converge at GSK3beta to
      control Myc protein stability, while our genetic analysis shows that insulin and
      TOR pathways have different requirements for Myc activity during development of
      the eye, suggesting that Myc might be differentially induced by these pathways
      during growth or proliferation of cells that make up the ommatidia.

PMID- 21951764
TI  - Early out-of-hospital non-invasive ventilation is superior to standard medical
      treatment in patients with acute respiratory failure: a pilot study.
AB  - OBJECTIVE: To assess in patients with acute respiratory failure (ARF) whether out
      of-hospital (OOH) non-invasive ventilation (NIV) is feasible, safe and more
      effective compared with standard medical therapy (SMT). PATIENTS AND
      INTERVENTIONS: Patients with OOH ARF were randomly assigned to receive either SMT
      or NIV. MEASUREMENTS AND RESULTS: Fifty-one patients were enrolled, 26 of whom
      were randomly assigned to SMT and 25 of whom received NIV. Two patients were
      excluded because of protocol violations. OOH NIV was safe and effective in all
      patients. In the SMT group, treatment was not effective in five of 25 patients
      who required OOH mechanical ventilation (p=0.05). Patients in the SMT group were
      admitted to an intensive care unit (ICU) more frequently (n=17) (p<0.05) and for
      longer periods (3.7+/-6.4 days) (p=0.03) compared with patients in the NIV group
      (n=9, 1.3+/-2.6 days). Six patients in the SMT group required subsequent
      inhospital intubation and invasive ventilation during their hospital stays; only
      one patient in the NIV group required intubation (p=0.10). In contrast, patients
      in the NIV group received NIV more frequently (n=14) in hospital compared with
      patients in the SMT group (n=5) (p<0.01). CONCLUSIONS: OOH NIV proved to be
      feasible, safe and more effective for the treatment of ARF compared with SMT. OOH
      NIV promotes inhospital treatment with NIV and may reduce the frequency and
      length of ICU stays. Because the risks of OOH emergency intubation can be
      avoided, NIV should be the first-line treatment in OOH ARF if no
      contraindications are present.

PMID- 21951765
TI  - Less is more. Possible ways to improve tuition of the recovery position.
AB  - AIM: To identify what 10-11-year-old children do and do not learn during a 10 min
      session teaching the recovery position, with a view to suggesting possible
      improvements in training. METHODS: Participants were 148 boys and 144 girls.
      Before intervention, safety knowledge was assessed in a pencil and paper test.
      198 children were taught the recovery position at a safety education centre.
      Three months later, their attempts to leave a casualty in a safe position were
      observed, and compared with the attempts of 94 children who had not received
      training. RESULTS: 19% of the control group and 31% of trained children
      successfully placed a casualty in the recovery position. Only two of the seven
      standard routine moves were used by more than 50% of trained children, namely
      raise the casualty's leg to a flexed position, roll the casualty on to his/her
      side. Even when performed, these and other individual moves were often not
      integrated into an effective routine. CONCLUSIONS: The implication is that in a
      short session it is over-ambitious to attempt to teach a complex routine. It is
      more realistic to focus on a few moves which are easily learnt. The present
      results suggest that these should be flexing the leg and rolling the casualty on
      to his/her side. In this study, simply improving the participants' performance of
      these two moves could increase the number of learners who are successful from
      less than a third to nearly 50%.

PMID- 21951766
TI  - Effective population size of natural populations of Drosophila buzzatii, with a
      comparative evaluation of nine methods of estimation.
AB  - Allozyme and microsatellite data from numerous populations of Drosophila buzzatii
      have been used (i) to determine to what degree N(e)  varies among generations
      within populations, and among populations, and (ii) to evaluate the congruence of
      four temporal and five single-sample estimators of N(e) . Effective size of
      different populations varied over two orders of magnitude, most populations are
      not temporally stable in genetic composition, and N(e)  showed large variation
      over generations in some populations. Short-term N(e)  estimates from the
      temporal methods were highly correlated, but the smallest estimates were the most
      precise for all four methods, and the most consistent across methods. Except for
      one population, N(e)  estimates were lower when assuming gene flow than when
      assuming populations that were closed. However, attempts to jointly estimate N(e)
      and immigration rate were of little value because the source of migrants was
      unknown. Correlations among the estimates from the single-sample methods
      generally were not significant although, as for the temporal methods, estimates
      were most consistent when they were small. These single-sample estimates of
      current N(e)  are generally smaller than the short-term temporal estimates.
      Nevertheless, population genetic variation is not being depleted, presumably
      because of past or ongoing migration. A clearer picture of current and short-term
      effective population sizes will only follow with better knowledge of migration
      rates between populations. Different methods are not necessarily estimating the
      same N(e) , they are subject to different bias, and the biology, demography and
      history of the population(s) may affect different estimators differently.

PMID- 21951767
TI  - Liver transplantation in Spanish haemophiliacs.

PMID- 21951768
TI  - Human leukocyte antigen class I on peripheral blood mononuclear cells as a non
      invasive biomarker for esophageal cancer.
AB  - Esophageal cancer (EC) is a common malignant cancer threatening people's health.
      There are no universally accepted parameters for its early diagnosis. The aim of
      this study was to observe the expression of human leukocyte antigen class I (HLA
      I) on peripheral blood mononuclear cells (PBMCs) of EC patients and in
      individuals of high-incidence area of EC so as to evaluate the feasibility of
      using this parameter as a potential non-invasive biomarker for the early
      diagnosis of EC. The present study enrolled 58 pathological confirmed EC
      patients, 46 patients with benign esophageal disease, and 65 healthy volunteers.
      Expression levels of HLA-I protein and mRNA on PBMCs were determined by flow
      cytometry and quantitative reverse transcriptase polymerase chain reaction,
      respectively. Then, 181 volunteers from Lijiadian, a village with high morbidity
      of EC, and 153 age- and gender-matched health volunteers were involved in this
      study to observe HLA-I expressions in individuals of high-incidence area of EC.
      Compared with benign esophageal disease and health volunteers, the expressions of
      HLA-I protein and mRNA on PBMCs of EC patients are significantly decreased,
      especially in patients with stage III and IV EC, but was not influenced by
      patient's age and gender. Furthermore, individuals of high-incidence area of EC
      also show downregulated HLA-I protein, but not mRNA, expression on PBMCs.
      Altogether, HLA-I expression on PBMCs of EC patients and individuals from high
      incidence area of EC is downregulated, and this parameter might be used as a
      potential predictor of EC.

PMID- 21951769
TI  - Football reminiscence for men with dementia: lessons from a realistic evaluation.
AB  - Football reminiscence for men with dementia: lessons from a realistic evaluation
      A major challenge of studies of non pharmacological dementia interventions is the
      likely modest intervention effect size and difficulties collecting data from
      individuals with behavioural, psychological and communicative symptoms. The
      reported Realist Evaluation is built around sets of contextually comparable case
      studies of Football Focussed Reminiscence for men with dementia. The study aim
      was to evaluate benefits of football related reminiscence for individuals and
      family carers. Four case studies were constructed; two community groups, one
      nursing home groups and individual sessions within their family home. Data was
      collected as field notes from non-participation observation of reminiscence
      sessions, notes of conversations with people with dementia, audio recorded
      interviews with family members, facilitators and dementia link workers. The
      analysis was framed around identification and extraction of data pertaining to
      Context-Mechanism-Outcome configurations within each data set, and patterns and
      threads were compared across the cases. An important finding was that
      anticipation of pleasure in tandem with a sense of continuity appeared to be
      important mechanisms triggering optimal benefit. The paper explores design
      considerations, project delivery experiences and the contribution that innovative
      theory driven research adds to the study of complex interventions including those
      with behavioural and communicative symptoms of dementia.

PMID- 21951770
TI  - Implementing knowledge into practice for improved neonatal survival; a cluster
      randomised, community-based trial in Quang Ninh province, Vietnam.
AB  - BACKGROUND: Globally, almost 4 million newborns die during the first 4 weeks of
      life every year. By increased use of evidence-based knowledge in the healthcare
      system a large proportion of these neonatal deaths could be prevented. But there
      is a severe lack of knowledge on effective methods for successful implementation
      of evidence into practice, particularly in low- and middle-income countries.
      Recent studies have demonstrated promising results with increased survival among
      both mothers and newborns using community-based approaches. In Vietnam evidence
      based guidelines on reproductive health were launched in 2003 and revised in
      2009. The overall objective of the current project is to evaluate if a
      facilitation intervention on the community level, with a problem-solving approach
      involving local representatives if the healthcare system and the community,
      results in improvements of neonatal health and survival. METHODS/DESIGN: The
      study, which has been given the acronym NeoKIP (Neonatal Health - Knowledge Into
      Practice), took place in 8 districts composed by 90 communes in a province in
      northern Vietnam, where neonatal mortality rate was 24/1000 in 2005. A cluster
      randomised design was used, allocating clusters, as defined as a commune and its
      correponding Commune Health Center (CHC) to either intervention or control arm.
      The facilitation intervention targeted staff at healthcare centres and key
      persons in the communes. The facilitator role was performed by lay women (Women's
      Union representatives) using quality improvement techniques to initiate and
      sustain improvement processes targeting identified problem areas. The
      intervention has been running over 3 years and data were collected on the
      facilitation process, healthcare staff knowledge in neonatal care and their
      behaviour in clinical practice, and reproductive and perinatal health indicators.
      Primary outcome is neonatal mortality. DISCUSSION: The intervention is
      participatory and dynamic, focused on developing a learning process and a problem
      solving cycle. The study recognises the vital role of the local community as
      actors in improving their own and their newborns' health, and applies a bottom-up
      approach where change will be accomplished by an increasing awareness at and
      demand from grass root level. By utilising the existing healthcare structure this
      intervention may, if proven successful, be well suited for scaling up. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN44599712.

PMID- 21951771
TI  - Cyclic vomiting syndrome and functional vomiting in adults: association with
      cannabinoid use in males.
AB  - BACKGROUND: Cyclic vomiting syndrome (CVS) is characterized by stereotypical
      episodes of vomiting separated by symptom-free intervals. However, the difficulty
      encountered in the management of patients with CVS may be a reflection of a
      deficiency in our understanding of the disorder. We aimed to evaluate whether
      clinical or gastric emptying (GE) data discriminate patients labeled as having
      CVS from functional vomiting (FV) or irritable bowel syndrome (IBS). METHODS: The
      medical records of patients diagnosed with any vomiting (including CVS, FV) over
      a 13-year period (1993-2006) at our institution were carefully reviewed. Disease
      controls were age and gender matched subjects with IBS. Gastric emptying was
      performed by scintigraphy (99mTc-egg meal). The associations of clinical factors
      and GE data with patient status (CVS vs FV or IBS) were analyzed. KEY RESULTS: A
      total of 82 patients with CVS and 62 FV patients were identified. Younger age
      [per 10 years, OR = 0.7 (0.5, 0.9)], male gender [OR = 0.4 (0.2, 0.9)], and
      cannabinoid use [OR = 2.9 (1.2, 7.2)] were significantly associated with CVS
      compared with FV. However, there were no significant associations between patient
      status (CVS vs FV) and age, BMI, smoking, alcohol use, gastrointestinal symptoms,
      or GE. The proportion of cannabinoid users was significantly higher in patients
      with CVS compared with patients with IBS, whereas proportions for headaches and
      psychiatric disease were higher in subjects with IBS. CONCLUSIONS & INFERENCES:
      Cyclic vomiting syndrome (vs FV) was not associated with clinical factors, but
      was associated with younger age, male gender and cannabinoid use. A larger
      proportion of CVS (vs IBS) patients had used cannabinoids.

PMID- 21951772
TI  - A guide to binary vectors and strategies for targeted genome modification in
      fungi using Agrobacterium tumefaciens-mediated transformation.
AB  - Agrobacterium tumefaciens-mediated transformation (ATMT) of fungi has become a
      common technique for the study of a wide variety of different fungal species over
      the past 12 years. The discovery that the host range of A. tumefaciens could be
      extended to include fungi provided an efficient transformation tool for species
      in which it was previously impossible to conduct molecular genetics experiments.
      ATMT experiments can be divided into three groups: i) Forward genetics (i.e.,
      random mutagenesis), ii) Reverse genetics (i.e., targeted genome modification and
      random integration) and iii) the introduction of reporter genes (e.g., GFP, RFP
      and GUS) that allow in situ monitoring of the fungus. The use of ATMT for forward
      genetics experiments has primarily included classic random insertional
      inactivation strategies to obtain loss-of-function mutants. For reverse genetics
      experiments, ATMT has been used to introduce targeted genome modifications (e.g.,
      disruptions, replacements, overexpression and complementation) and to generate
      random integrations for complementation, heterologous expression, expression of
      transcriptional and translational fusion reporters and RNAi-mediated down
      regulation of gene expression. This review summarizes the technical advances
      within the field from 1998 to the summer of 2011, focusing on the development of
      binary vectors that are compatible with fungal transformation (over 180 general
      vectors) and methods for constructing binary vectors for targeted integration of
      T-DNA into fungal genomes.

PMID- 21951774
TI  - Gender difference in psychogeriatric disorders.

PMID- 21951773
TI  - Perianal basal cell carcinoma - unusual localization of a frequent tumor.
AB  - Basal cell carcinoma is the most common human neoplasia. In more than 80% of
      patients, who are predominantly elderly, it is located in the head-and-neck-area.
      Basal cell carcinomas in non-UV-exposed areas of the body, such as the anogenital
      region, are dermatological rarities. We describe an 88-year-old patient with a
      perianal tumor that was detected during skin cancer screening. Histopathology
      showed the tumor to be a basal cell carcinoma. Immunohistochemical staining for
      Ber-EP4 was highly positive, clearly distinguishing the tumor from basaloid anal
      carcinoma, which is the most important histological differential diagnosis.
      Additional virological analyses for human papil-lomaviruses (HPV) were negative.
      Immunohistochemical staining for p16(INK4a)  demonstrated strong expression in
      the cells of the tumor parenchyma. However, p16(INK4a)  can also be expressed
      independently of HPV. The present case shows that all uncertain perianal skin
      lesions should be biopsied.

PMID- 21951775
TI  - Guidelines for non-medical care providers to manage the first steps of emergency
      triage of elderly evacuees.
AB  - On 11 March 2011, a strong earthquake occurred off of Japan's Pacific coast and
      hit northeastern Japan. The earthquake was followed by huge tsunamis, which
      destroyed many coastal cities. As a result, the Study Group on Guidelines for the
      First Steps and Emergency Triage to Manage Elderly Evacuees quickly established
      guidelines enabling non-medical care providers (e.g. volunteer, helpers, and
      family members taking care of elderly relatives), public health nurses, or
      certified social workers to rapidly detect illnesses in elderly evacuees, and 20
      000 booklets were distributed to care providers in Iwate, Miyagi, and Fukushima
      prefectures. The aim of this publication is to reduce susceptibility to disaster
      related illnesses (i.e. infectious diseases, exacerbation of underlying
      illnesses, and mental stress) and deaths in elderly evacuees.

PMID- 21951776
TI  - Actions of the Japan Geriatric Society in response to the 2011 off the Pacific
      Coast of Tohoku Earthquake: first report.

PMID- 21951777
TI  - Novel approach to ischemic skin ulcer in systemic lupus erythematosus:
      therapeutic angiogenesis by controlled-release basic fibroblast growth factor.

PMID- 21951778
TI  - Self-rated happiness is associated with functional ability, mood, quality of life
      and income, but not with medical condition in community-dwelling elderly in
      Japan.

PMID- 21951779
TI  - Bile duct hamartomas (von Meyenburg complexes) associated with a bacterial
      infection: case report of elderly diabetic patient.

PMID- 21951780
TI  - 18F-Fluorodeoxyglucose positron emission tomography/computed tomography revealed
      the presence of simultaneous colon cancer in mucosa-associated lymphoid tissue
      lymphoma.

PMID- 21951781
TI  - Expression of opioid and anti-opioid receptors in Chinese hamster ovary cells
      after exposure to dimethyl sulfoxide.
AB  - Functional and structural studies on G-protein-coupled receptors (GPCRs) at
      molecular levels require producing and purifying high levels of receptors, and
      recombinant mammalian cell expression systems constitute the best systems to
      obtain receptors resembling those expressed in natural environments. In the
      course of increasing GPCR expression in Chinese hamster ovary (CHO) cells, we
      have expressed mu (MU)- and kappa (kappa)-opioid receptors and neuropeptide FF(1)
      and FF(2) receptors (NPFF(1) and NPFF(2), respectively) in dimethyl sulfoxide.
      This treatment did not modify the affinity (K(d)) for any receptor, but a
      significant increase in functional expression levels was observed for all
      receptors with the noticeable exception of NPFF(1).

PMID- 21951782
TI  - Chitosan functionalized magnetic particle-assisted detection of genetically
      modified soybeans based on polymerase chain reaction and capillary
      electrophoresis.
AB  - The high quality of DNA template is one of the key factors to ensure the
      successful execution of polymerase chain reaction (PCR). Therefore, development
      of DNA extraction methods is very important. In this work, chitosan modified
      magnetic particles (MPs) were synthesized and employed for extraction of genomic
      DNA from genetically modified (GM) soybeans. The extraction protocol used aqueous
      buffers for DNA binding to and releasing from the surface of the MPs based on the
      pH inducing the charge switch of amino groups in chitosan modified MPs. The
      extracted DNA was pure enough (A(260)/A(280)=1.85) to be directly used as
      templates for PCR amplification. In addition, the PCR products were separated by
      capillary electrophoresis for screening of GM organisms. The developed DNA
      extraction method using chitosan modified MPs was capable of preparation of DNA
      templates, which were PCR inhibitor free and ready for downstream analysis. The
      whole process for DNA extraction and detection was preferable to conventional
      methods (phenol-chloroform extraction, PCR, and gel electrophoresis) due to its
      simplicity and rapidity as well as its avoiding the use of toxic reagents and PCR
      inhibitors.

PMID- 21951783
TI  - L-amino acid oxidase-induced apoptosis in filamentous Botrytis cinerea.
AB  - As opposed to single-cell yeast and mammalian cell lines, apoptosis has not been
      greatly investigated in filamentous fungi because antibodies to the relevant
      fungal apoptosis-related proteins are not available commercially and because
      multicellular organisms cannot be studied using flow cytometry. Here we
      demonstrate how antibodies from a nonfungal source could be used to investigate
      this pathway. We show that apoptosis in the filamentous fungus Botrytis cinerea
      is triggered by the mitochondria-mediated caspase pathway, with release of the
      apoptotic factors cytochrome c, caspase 3, and caspase 9, on treatment with
      Trichoderma harzianum-derived L-amino acid oxidase.

PMID- 21951784
TI  - Analysis of oligomeric stability of insulin analogs using hydrogen/deuterium
      exchange mass spectrometry.
AB  - Insulin analog products for subcutaneous injection are prepared as solutions in
      which insulin analog molecules exist in several oligomeric states. Oligomeric
      stability can affect their onset and duration of action and has been exploited in
      designing them. To investigate the oligomeric stability of insulin analog
      products having different pharmacokinetics, we performed hydrogen/deuterium
      exchange mass spectrometry (HDX/MS), which is a rapid method to analyze dynamic
      aspects of protein structures. Two rapid-acting analogs (lispro and glulisine)
      incorporated deuteriums more and faster than recombinant human insulin, whereas a
      long-acting analog (glargine) and two intermediate-acting preparations (protamine
      containing formulations) incorporated them less and more slowly. Kinetic analysis
      revealed that the number of slowly exchanged hydrogens (D(s)) (k<0.01 min(-1))
      accounted for the difference in HDX reactivity among analogs. Furthermore, we
      found correlations between HDX kinetics and pharmacokinetics reported previously.
      Their maximum serum concentration (C(max)) was linearly correlated with D(s)
      (r=0.88) and the number of maximum exchangeable hydrogens (D(infinity)) (r=0.89).
      The maximum drug concentration time (t(max)) was also correlated with reciprocals
      of D(s) and D(infinity) (r=0.86 and r=0.96, respectively). Here we demonstrate
      the ability of HDX/MS to evaluate oligomeric stability of insulin analog
      products.

PMID- 21951785
TI  - Detection of metabolites in the white matter of frontal lobes and hippocampus
      with proton in first-episode treatment-naive schizophrenia patients.
AB  - AIM: This study aimed to investigate the changes of the metabolites in the white
      matter of frontal lobes and hippocampus in schizophrenia by using proton magnetic
      resonance spectroscopy ((1) H-MRS). METHODS: Sixty-three first-episode treatment
      naive schizophrenia (FES) patients and 63 age-, gender- and education level
      matched healthy controls were recruited. The relative levels of metabolites
      including N-acetylaspartate (NAA), choline-containing compounds (Cho), (Cr) and
      myo-inositol (MI) were detected with (1) H-MRS, and the laterality index (Li) was
      calculated. The severity of symptoms was assessed using the Positive and Negative
      Syndrome Scale. RESULTS: Compared with controls, FES patients did not show
      significant differences in all metabolites. The severity of positive symptoms was
      negatively correlated with the NAA/Cho in the white matter of the left frontal
      lobe and positively correlated with the Cho/Cr in the right white matter of
      frontal lobes. A negative correlation was observed between the severity of
      negative symptoms and the NAA/Cr in the white matter of bilateral frontal lobes.
      No difference was shown in the Li of metabolites between FES patients and
      controls. CONCLUSIONS: The metabolites such as NAA, Cho and MI in white matter of
      frontal lobes and hippocampus were not significantly altered in FES patients. The
      lower axonal integrity/number (NAA concentration) may be associated with more
      severe negative symptoms, and dysmetabolism in process of myelination in the
      white matter of frontal lobes associated with more severe positive symptoms.

PMID- 21951786
TI  - Mhp182 (P102) binds fibronectin and contributes to the recruitment of
      plasmin(ogen) to the Mycoplasma hyopneumoniae cell surface.
AB  - Mycoplasma hyopneumoniae is a major, economically damaging respiratory pathogen.
      Although M. hyopneumoniae cells bind plasminogen, the identification of
      plasminogen-binding surface proteins and the biological ramifications of
      acquiring plasminogen requires further investigation. mhp182 encodes a highly
      expressed 102 kDa protein (P102) that undergoes proteolytic processing to
      generate surface-located N-terminal 60 kDa (P60) and C-terminal 42 kDa (P42)
      proteins of unknown function. We show that recombinant P102 (rP102) binds
      plasminogen at physiologically relevant concentrations (K(D) ~ 76 nM) increasing
      the susceptibility of plasmin(ogen) to activation by tissue-specific plasminogen
      activator (tPA). Recombinant proteins constructed to mimic P60 (rP60) and P42
      (rP42) also bound plasminogen at physiologically significant levels. M.
      hyopneumoniae surface-bound plasminogen was activated by tPA and is able to
      degrade fibrinogen, demonstrating the biological functionality of M.
      hyopneumoniae-bound plasmin(ogen) upon activation. Plasmin(ogen) was readily
      detected in porcine ciliated airways and plasmin levels were consistently higher
      in bronchoalveolar lavage fluid from M. hyopneumoniae-infected animals.
      Additionally, rP102 and rP42 bind fibronectin with K(D) s of 26 and 33 nM
      respectively and recombinant P102 proteins promote adherence to porcine kidney
      epithelial-like cells. The multifunctional binding ability of P102 and activation
      of M. hyopneumoniae-sequestered plasmin(ogen) by an exogenous activator suggests
      P102 plays an important role in virulence.

PMID- 21951787
TI  - Comparative effectiveness in pain-related outcomes and health care utilizations
      between veterans with major depressive disorder treated with duloxetine and other
      antidepressants: a retrospective propensity score-matched comparison.
AB  - OBJECTIVES: This study aimed to compare pain-related outcomes and health care
      utilization among patients with major depressive disorder (MDD) treated with
      duloxetine versus other antidepressants in the Veterans Health Administration
      (VHA). METHODS: Patients initiating duloxetine or other antidepressants between
      October 1, 2005, and October 1, 2008 were extracted from the Veterans Integrated
      Service Network (VISN) 16 data warehouse. All patients included had at least 1
      MDD diagnosis (ICD-9-CM: 296.2 or 296.3) and continuous eligibility in the 12
      months prior to the initiation. Patients with prior diabetes (ICD-9-CM: 250.xx),
      schizophrenia (295.xx), or bipolar disorder (ICD-9-CM: 296.4x-296.8x) diagnosis
      were excluded. Duloxetine and nonduloxetine patients were matched via propensity
      scoring (1:1 ratio). Opioid use patterns, diagnosed substance abuse, self
      reported pain score, and health care utilization over the 12-month postindex
      period were compared between cohorts. RESULTS: Compared with duloxetine-treated
      patients (N = 439), nonduloxetine-treated patients (N = 439) during the postindex
      period had more opioid scripts (4.8 vs. 3.6, P = 0.002), longer use of opioid
      (133 vs. 100 days, P = 0.004), and a higher prevalence of substance abuse (41.00%
      vs. 23.69%, P < 0.001). Nonduloxetine-treated group had 12.0 more outpatient
      visits (41.8 vs. 29.8, P < 0.0001), 0.16 more hospital admissions (0.32 vs. 0.16,
      P = 0.001), and 2.36 more hospital days (3.37 vs. 1.01, P= 0.005). Additionally,
      nonduloxetine-treated patients were more likely to be hospitalized (17.8% vs.
      10.9%, P = 0.004) over the postindex period. CONCLUSION: Controlling for cross
      cohort differences, veterans with MDD treated with duloxetine were associated
      with lower risks of opioid use and substance abuse and lower health care
      utilization than those treated with other antidepressants. ?

PMID- 21951789
TI  - [Current status of SNPs interaction in genome-wide association study].
AB  - Identifying genetic variants associated with complex diseases/traits via genome
      wide single nucleotide polymorphisms (SNPs) has proved to be a new and efficient
      method for studying genetics. With a large number of achievements of genome-wide
      association study (GWAS), researchers have focused on performing genome-wide SNPs
      interaction analysis. The search for interaction effects is marked by an
      exponential growth, not only in terms of methodological development, practical
      applications and translation of statistical interaction to biological
      interaction, but also in terms of integration of omics information sources. Many
      strategies and methods have been applied in detecting interaction analysis, which
      provides new insights into genetics basis of complex diseases/traits. In this
      review based on the theory and algorithm realizations, the statistical methods
      have been sorted into regression, machine learning, Bayesian model, SNP filtering
      methods and parallel processing methods. Especially, the principle, efficiency
      and difference of the methods are summarized to offer references to the
      researchers in this field.

PMID- 21951788
TI  - From RNA-seq to large-scale genotyping - genomics resources for rye (Secale
      cereale L.).
AB  - BACKGROUND: The improvement of agricultural crops with regard to yield,
      resistance and environmental adaptation is a perpetual challenge for both
      breeding and research. Exploration of the genetic potential and implementation of
      genome-based breeding strategies for efficient rye (Secale cereale L.) cultivar
      improvement have been hampered by the lack of genome sequence information. To
      overcome this limitation we sequenced the transcriptomes of five winter rye
      inbred lines using Roche/454 GS FLX technology. RESULTS: More than 2.5 million
      reads were assembled into 115,400 contigs representing a comprehensive rye
      expressed sequence tag (EST) resource. From sequence comparisons 5,234 single
      nucleotide polymorphisms (SNPs) were identified to develop the Rye5K high
      throughput SNP genotyping array. Performance of the Rye5K SNP array was
      investigated by genotyping 59 rye inbred lines including the five lines used for
      sequencing, and five barley, three wheat, and two triticale accessions. A
      balanced distribution of allele frequencies ranging from 0.1 to 0.9 was observed.
      Residual heterozygosity of the rye inbred lines varied from 4.0 to 20.4% with
      higher average heterozygosity in the pollen compared to the seed parent pool.
      CONCLUSIONS: The established sequence and molecular marker resources will improve
      and promote genetic and genomic research as well as genome-based breeding in rye.

PMID- 21951790
TI  - [Mutations in mitochondrial DNA associated with hypertension].
AB  - Mutations in mitochondrial DNA (mtDNA) are one of the molecular bases of
      hypertension. Among these, the tRNAMet A4435G, tRNAMet/tRNAGln A4401G, tRNAIle
      A4263G, T4291C and A4295G mutations have been reported to be associated with
      essential hypertension. These mutations alter the structure of the corresponding
      mitochondrial tRNAs and cause failures in tRNA metabolism. These shortages of
      these tRNAs lead to an impairment of mitochondrial protein synthesis and a
      failure in the oxidative phosphorylation function. These result in a deficit in
      ATP synthesis and an increase of generation of reactive oxygen species. As a
      result, these mitochondrial dysfunctions may contribute to the development of
      hypertension. Furthermore, the tissue specificity of these pathogenic mtDNA
      mutations might be associated with tRNA metabolism and nuclear modifier genes.
      These mtDNA mutations should be considered as inherited risk factors for future
      molecular diagnosis. Thus, these findings provide new insights into the molecular
      mechanism, management and treatment of maternally inherited hypertension. This
      review summarized the association between mtDNA mutations and hypertension.

PMID- 21951791
TI  - [Epigenetic mechanisms of the influence of maternal care on off spring
      development].
AB  - It has been demonstrated that the social environment early in life has a long
      lasting effect on the physical and psychological health of the human body.
      However, understanding of the relationship between early life experiences, such
      as maternal care behavior, and life-long cognitive and emotional health can only
      rely on the studies on animal models. In this paper, we summarized the maternal
      care effects on both defensive responses to stress and reproductive behavior in
      rat, and explored the possible underlying epigenetic mechanisms for these
      effects. Based on this model, we further investigated the significance of such
      epigenetic effects on human mental health.

PMID- 21951792
TI  - [Current status and development of miRNA and siRNA research on gastric cancer].
AB  - RNA interference (RNAi) is an important topic of epigenetics research in post
      genome period. RNAi works as a post-DNA replication regulator for gene
      expression, and it is related to the occurrence and development of malignant
      tumors. The most usual participators of RNAi are MicroRNA (miRNA) and small
      interference RNA (siRNA). This review summarizes the basic theory of miRNA and
      siRNA, and provides recent progresses of RNAi research on gastric cancer. RNAi
      analysis and technique not only act as powerful tools for studying gene function
      and action mechanism, but also have diagnostic and therapeutic potential in
      gastric cancer, even in all kinds of tumors.

PMID- 21951793
TI  - [The role of Pax2 in regulation of kidney development and kidney disease].
AB  - Paired box2 (Pax2) gene plays a crucial role in kidney development and is
      expressed in the nephric duct, mesenchyme of pronephrons, mesonephrons, and
      metanephrons with special spatial and temporal characteristic. Research in
      animals indicate that Pax2 can interact with many important transcription factors
      such as Gdnf, Ret, SHH, Wnt4, and Fgf to organize the nephric linage
      specification, pro/mesonephric tubule formation and descent, emergence of the
      ureteric bud, branching morphogenesis, and nephron induction. Pax2 is associated
      with various congenital renal and ureter malformations, and the mutation is
      easist to detected in Renal-coloboma syndrome. In renal cell carcinoma, Wilms
      tumor and many acquired kidney diseases Pax2 is expressed abnormally, whose
      diagnose and therapy value will be the focus of further research. This paper
      reviews the molecular structure, expression and regulation of Pax2 in kidney
      development and diseases.

PMID- 21951794
TI  - [Methylation and acetylation of histones during spermatogenesis].
AB  - Spermatogenesis is a highly complex and unique differentiation process. This
      process involves development of spermatogonia into spermatocytes, formation of
      haploid spermatids, and maturation of spermatozoa. It features stage- and testis
      specific gene expression, mitotic and meiotic divisions, and the histone
      protamine transition. The epigenetic modification plays an important role in
      meiotic recombination, formation of the synaptonemal complex, sister chromatid
      cohesion, spermiogenesis during postmeiotic stages, gene expression repression,
      and heterochromatin formation. The mark of the repressive and/or activating
      histone methylation and acetylation has a defined composition. It not only
      ensures proper chromosome pairing and successful bivalent segregation but also
      mediates highly orchestrated expression of meiosis-specific genes. The incorrect
      histone methylation and/or acetylation during spermatogenesis will directly
      affect the establishment and maintenance of epigenetic patterns, resulting in
      abnormal spermatogenic cells and even male infertility. This article is an effort
      to review the dynamic changes of methylation and acetylation of histones during
      spermatogenesis, as well as the regulatory mechanism of the enzymes involved in
      these processes, which provides some basic information for further study of the
      epigenetic events during spermatogenesis and the prevention of male infertility.

PMID- 21951795
TI  - [Study progress of special AT-rich sequence binding protein 2].
AB  - SATB2 is a transcription factor, which plays an important role in transcriptional
      regulation and chromatin recombinant by combining with matrix attachment regions.
      SATB2 is a key regulatory molecule in the progress of osteoblast differentiation
      and bone matrix formation. Mutations in this gene are associated with congenital
      craniofacial malformation. In addition, SATB2 is involved in the development of
      central nervous system, especially the corpus callosum and the pons. At the same
      time, SATB2 may participate in the process of tumor formation. In malignant
      tumors, such as breast cancer, the expression level of SATB2 is higher than
      normal. The literatures of SATB2 were reviewed in this article.

PMID- 21951796
TI  - [Progress in exploring genes for high fertility in ewes].
AB  - Fecundity trait in sheep is regulated by some major genes. Among them, BMPR-IB,
      BMP-15, and GDF-9 are most distinguishing. The mutant FecB of BMPR-IB has
      multiplicative effects on ovulation. GDF-9's mutants FecGH, FecI, and BMP-15's
      mutants FecXI, FecXH, FecXG, FecXB, FecXL, and FecXR increase ovulation rate in
      the heterozygote but result in sterile phenotypes in the homozygote, while GDF
      9's mutant, FecGE, only increases ovulation rate in the homozygote. In addition,
      Woodlands and Lacaune are known as inheritable major genes. Woodlands gene is an
      X-linked maternally imprinted gene, and Lacaune is similar to FecB with a
      multiplicative effect on ovulation rate. The size of the effect of one copy of a
      mutation on ovulation rate ranges from an extra 0.4 ovulations for the woodlands
      mutation to an extra 1.5 ovulations for the BMPR-IB and Lacaune mutation.
      Investigation into these genes will not only help to select breeds with high
      fertility, but also give a chance to further elucidate the mechanism involved in
      the phenomenon. This review summaries the source, location, phenotype, and
      mechanism of the major genes in all breeds of sheep.

PMID- 21951797
TI  - [Current status and industrialization of transgenic tomatoes].
AB  - In this review, the progress in transgenic tomato research, including disease and
      insect resistance, herbicide resistance, stress tolerance, long-term storage,
      quality improvement, and male sterility, were described. The recent researches on
      producing heterologous proteins using transgenic tomatoes were also reviewed.
      Furthermore, the industrialization status and problems of transgenic tomatoes
      were analyzed and the prospects of both research and industrialization in
      transgenic tomatoes were discussed.

PMID- 21951798
TI  - [Properties comparing and evolutionary analysis of MEF2 of Homo sapiens based on
      bioinformatic methods].
AB  - As one of the members of MADS family, MEF2 group is important in regulating
      development. Analytical tools of NCBI, ExPASy, CBS, CDD, and SABLE were adopted
      to analyze the properties of human MEF2 proteins, and evolutionary tree was built
      according to the result of correlative sequence alignments. The results showed
      that there are various forms of MEF2 in human body, and there are some
      differences in the physicochemical characteristics. Relatively more
      phosphorylation sites are found and the main glycosylation sites are N
      glycosylation sites. All MEF2 proteins of human contain MADS domain, and most
      contain MEF2 domain and HJURP_C domain. Their secondary structures contain three
      dominant states: helix, sheet and coil, their tertiary structures are similar.
      The phylogenetic tree result shows that MEF2B may be original because of its
      difference of sequences and evolutional relation.

PMID- 21951799
TI  - [Cloning, expression analysis and RNA interference of FGF5 gene in sheep].
AB  - The cDNA of fibroblast growth factor 5 (FGF5) gene in sheep was cloned, and the
      nucleotides sequence homology of FGF5 was compared with other six mammal. In
      addition, the expression of FGF5 in different tissues was analysed. Gene FGF5 was
      then recombined into prokaryotic expression vector (pGEX-4T-2) and RNA
      interference vector (pSilencer 5.1 H1) to study its expression in fibroblast cell
      lines. Results showed that the open reading frame (ORF) of cDNA in sheep
      consisted of 813 nucleotide acids encoding 270 amino acids, with the molecular
      mass of 29.58 kDa and theoretical pI of 10.59. The amino acids sequence of FGF5
      gene in sheep shared high identity with those in cow, human, mouse, rat, dog, cat
      and rabbit. In addition, analysis on tissue expression showed that FGF5 expressed
      in skin, heart, kidney, liver, pancreas, spleen, lung, and small intestine,
      especially presenting high levels in skin. The expression of FGF5 in E. coli was
      induced with IPTG, which produced a protein band with the expected size of 56 kDa
      on SDS-PAGE, while the expression of FGF5 in sheep fibroblast cell line was
      knocked down remarkably with the help of integrated RNAi vector.

PMID- 21951800
TI  - [Enrichment and screening of the microsatellite markers in Microtus fortis and
      its preliminary application in genetic diversity research].
AB  - This study was to isolate microsatellite markers from Microtus fortis genome by
      magnetic beads enrichments. Through hybridization of biotin-labeled
      microsatellite oligonucleotide probes, which were captured by streptavidin-coated
      magnetic with the adaptor-ligated enzyme-digested genome fragments, single
      stranded DNA fragments containing microsatellites were obtained. After PCR
      amplification, these fragments were then cloned into T vectors and were
      transformed into competent cells subsequently. Ninety-two microsatellite
      sequences were randomly isolated from 70 positive clones. Twenty-one out of 27
      pairs of designed microsatellite primers were screened out from the
      microsatellite sequences, and 10 out of the 21 microsatellite loci were used to
      investigate the genetic diversity of three populations of M. fortis, Hunan
      (wild), Hunan (domesticated), and Ningxia (domesticated). All the 10
      microsatellite loci used to analyze the genetic diversity exhibited a good level
      of polymorphism. The values of observed number of alleles (Na), effective number
      of alleles (Ne), observed heterozygosity (Ho), expected heterozygosity (He) and
      polymorphic information content (PIC) were all the highest in the Hunan (wild)
      population, lower in the Hunan (domesticated) population, and the lowest in the
      Ningxia (domesticated) population.

PMID- 21951801
TI  - [Polymorphism of SNPs in the lipoprotein lipase (LPL) in Siniperca chuatsi and
      their association with feed habit domestication].
AB  - Sinperca chuatsi usually refuses eating dead bait or man-made feed due to its
      specific feeding habit. It was showed that some S. chuatsi could be induced to
      take lifeless bait with domestication gradually after long-term of cultivation.
      High cost, serious pollution, severe diseases, and other problems of S chuatsi
      cultivation can be solved effectively by selecting those liable to domestication
      via molecular marker and treating them with artificial feed on a large scale.
      Lipoprotein lipase, one of the key enzymes in lipoprotein metabolic processes,
      provides energy by catalyzing the oxidation of triglycerides lie in the core of
      chylomicron and very low density lipoprotein (VLDL) into glycerin and fatty acid,
      and saves energy. In order to search the distribution of the alleles and
      genotypes of lipoprotein lipase gene (lipoprotein LPL) gene in two feed habit
      domestication phenotype populations, SNP genetic polymorphisms in 6 and 7 introns
      and 6, 7, and 8 exons of LPL in S. chuatsi were analyzed by PCR product
      sequencing method. Three SNPs A25T, G26T, and C29G were detected, two of which
      were non-synonymous mutations. It was indicated by Chi-square test that the
      analysis between domesticated and undomesticated populations show no significant
      difference (P>0.05) between the three SNPs and feed habit. However, diplotype 2
      in the two population showed significant difference (P<0.05) by assembling
      different genotypes of the three SNPs into five diplotypes. Polymorphic analysis
      of partial fragment of LPL genome in S. chuatsi was accomplished successfully.
      Therefore, LPL gene can be considered as a candidate gene and genetic marker for
      feed habit domestication in S. chuatsi, which lays the foundation for the work of
      molecular marker and selecting breed, which has extensive application prospect.

PMID- 21951802
TI  - [Genetic screening and analysis of suppressors of asa1-1 (soa) defective in
      jasmonate-mediated lateral root formation in Arabidopsis].
AB  - It has been shown that jasmonate modulates the lateral root development through
      crosstalk with auxin in Arabidopsis thaliana. Exogenous application of jasmonate
      stimulates lateral root formation in wild type but inhibits lateral root
      formation in asa1-1. Our previous work has demonstrated that the lateral root
      formation defect of asa1-1 is co-related with jasmonte effect on PIN2 protein
      levels. To further elucidate the molecular mechanisms underlying jasmonate
      mediated reduction of plasma membrane (PM)-resident PIN2 abundance, we have
      conducted a genetic screen to identify suppressors of asa1-1 (soa), which showed
      lateral root formation in the presence of jasmonate. Here, we described the basic
      characterization of soa563 and soa856. We showed that both soa563 and soa856
      displayed restored lateral root formation in response to exogenous jasmonate. In
      addition, jasmonate-induced PIN2:GFP reduction was blocked in these two mutants.
      Our on-going effort to identify genes defined by these mutants promise to shed
      new light on the understanding of the molecular mechanisms controlling jasmonate
      mediated regulation of PIN2 protein trafficking and turnover.

PMID- 21951803
TI  - [Construction and analysis of the SSH library with the resistant wheat near
      isogenic line and its susceptible parent infected by Puccinia striiformis
      Westend. f. sp. tritici].
AB  - To analyze the differentially expressed genes between resistant and susceptible
      wheat near-isogenic lines infected by Puccinia striiformis Westend. f. sp.
      tritici, a subtractive library containing about 1300 clones was constructed using
      suppression subtractive hybridization (SSH) in which the cDNA from resistant
      Yr4/6 * Taichung 29 seedlings inoculated with race CY26 was used as the tester,
      and the corresponding cDNA from susceptible Taichung 29 as the driver. Six
      hundred clones from the library were analyzed with reverse Northern blot. The
      positive clones were further tested by Northern blotting analysis. Twelve clones
      were verified and showed significant difference. By means of sequencing and
      BlastX analysis, six function-known differentially expressed sequences were
      detected, and their putative products were leucine-rich repeat protein, catalase,
      thioredoxin H-type, RNA binding protein, ascorbate peroxidase, and heat shock
      protein, respectively. Among them, leucine-rich repeat protein belongs to signal
      transduction protein, and others belong to defense response protein.

PMID- 21951804
TI  - [Techniques for rapid preparation of tomato leaf DNA and its application in real
      time quantitative PCR-based transgene detection].
AB  - Using tomato (Solanum lycopersicum L. cv. Micro-Tom) leaf as material, a simple
      and rapid DNA preparation protocol was established. This method required only 2
      20 mm2 leaf with only one extraction solution and involved one pipetation and one
      centrifugation each. No precipitation was required. The suitable volume of
      prepared DNA solution, as PCR template, for real-time quantitative PCR was
      determined to be 0.1?0.2 MUL in 12.5 MUL final reaction volume. The excessive
      template DNA solution was confirmed to reduce PCR efficiency and even can result
      in PCR failure. This technique for rapid preparation of DNA and a compatible real
      time quantitative PCR were successfully applied in transgene detection of tomato
      plants.

PMID- 21951805
TI  - [Repetition of teaching contents between genetics and relative courses in
      agricultural and forestry colleges and approaches to solving the problem].
AB  - Genetics is one of the main courses in agricultural and forestry colleges.
      However, there is large repetition of teaching contents and joining problems
      between genetics and the relative courses. The negative effects of above problems
      are discussed in this paper. In order to relieve the conflict between the
      increase of genetics contents and the decrease of teaching hours in genetics
      teaching of undergraduates and provide reference for future textbook compilation,
      some approaches on solving repetition of teaching content and suggestions on
      joining problems are put forward.

PMID- 21951806
TI  - Age-related beta-adrenergic receptor-mediated vasorelaxation is changed by
      altering G protein receptor kinase 2 expression.
AB  - Beta-adrenergic receptor- (beta-AR) mediated vasorelaxation declines with age.
      This change is likely related to receptor desensitization, rather than down
      regulation. One kinase responsible for desensitization is G protein receptor
      kinase 2 (GRK2). We have shown that GRK expression and activity increases with
      age in Fischer 344 rat aorta. In this study we validated that carotid arteries
      have similar age-related changes in the beta-AR signaling axis as aorta. This
      finding allowed use of in vivo infection and delivery of two adenovirus vectors
      to carotid arteries of 2-month-old (2M) and 12-month-old (12M) male Fischer 344
      rats. Adeno-GRK2 was used to overexpress GRK2, and adeno-beta-ARK-ct was used to
      inhibit GRK2 function. Following a five-day infection, vessels were collected and
      ex vivo tissue bath was used to evaluate vasoreactivity. We used KCl contracted
      segments, and determined that overexpression of GRK2 significantly impaired
      isoproterenol (ISO)-mediated vasorelaxation in both age groups. Maximum
      relaxation (MAX) to ISO in vessels from 2M decreased from 44% to 21%. MAX to ISO
      in vessels from 12M decreased from 12% to 6%. Sensitivity (ED50) in vessels from
      2M and 12M was also impaired 57%, and 30% respectively. We also determined that
      expression of adeno-beta-ARK-ct significantly improved ISO-mediated
      vasorelaxation in both age groups. MAX in vessels from 2M increased from 44% to
      58%. MAX in vessels from 12M increased from 15% to 69%. ED50 in vessels from 2M
      and 12M was also improved 46%, and 50% respectively. These findings further
      implicate age-related increases in GRK2 expression as an important regulator of
      the age-related decline in beta-AR-mediated vasorelaxation.

PMID- 21951808
TI  - The ezetimibe Jonah: the trials and tribulations of an unlucky drug.

PMID- 21951807
TI  - Effect of flow on endothelial endocytosis of nanocarriers targeted to ICAM-1.
AB  - Delivery of drugs into the endothelium by nanocarriers targeted to endothelial
      determinants may improve treatment of vascular maladies. This is the case for
      intercellular adhesion molecule 1 (ICAM-1), a glycoprotein overexpressed on
      endothelial cells (ECs) in many pathologies. ICAM-1-targeted nanocarriers bind to
      and are internalized by ECs via a non-classical pathway, CAM-mediated
      endocytosis. In this work we studied the effects of endothelial adaptation to
      physiological flow on the endocytosis of model polymer nanocarriers targeted to
      ICAM-1 (anti-ICAM/NCs, ~180 nm diameter). Culturing established endothelial-like
      cells (EAhy926 cells) and primary human umbilical vein ECs (HUVECs) under 4
      dyn/cm(2) laminar shear stress for 24 h resulted in flow adaptation: cell
      elongation and formation of actin stress fibers aligned to the flow direction.
      Fluorescence microscopy showed that flow-adapted cells internalized anti-ICAM/NCs
      under flow, although at slower rate versus non flow-adapted cells under static
      incubation (~35% reduction). Uptake was inhibited by amiloride, whereas
      marginally affected by filipin and cadaverine, implicating that CAM-endocytosis
      accounts for anti-ICAM/NC uptake under flow. Internalization under flow was more
      modestly affected by inhibiting protein kinase C, which regulates actin
      remodeling during CAM-endocytosis. Actin recruitment to stress fibers that
      maintain the cell shape under flow may delay uptake of anti-ICAM/NCs under this
      condition by interfering with actin reorganization needed for CAM-endocytosis.
      Electron microscopy revealed somewhat slow, yet effective endocytosis of anti
      ICAM/NCs by pulmonary endothelium after i.v. injection in mice, similar to that
      of flow-adapted cell cultures: ~40% (30 min) and 80% (3 h) internalization.
      Similar to cell culture data, uptake was slightly faster in capillaries with
      lower shear stress. Further, LPS treatment accelerated internalization of anti
      ICAM/NCs in mice. Therefore, regulation of endocytosis of ICAM-1-targeted
      nanocarriers by flow and endothelial status may modulate drug delivery into ECs
      exposed to different physiological (capillaries vs. arterioles/venules) or
      pathological (ischemia, inflammation) levels and patterns of blood flow.

PMID- 21951809
TI  - Pro-inflammatory chemokine C-C motif ligand 16 (CCL-16) dysregulation in
      irritable bowel syndrome (IBS): a pilot study.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a serious health problem that
      affects an estimated 10-15% of people worldwide and has economic consequences in
      the United States of over $30 billion annually. In the US, IBS affects all races
      and both sexes, with more females than males (2:1) reporting symptoms consistent
      with IBS. Although the etiology of this functional gastrointestinal disorder is
      unknown, literature suggests that a subclinical inflammatory component has a role
      in the etiologic mechanisms underlying IBS. The aim of this study was to evaluate
      the gene expression of inflammatory biomarkers in patients with and without IBS
      and among different IBS phenotypes. METHODS: Irritable bowel syndrome patients
      (n=12) that met Rome III Criteria for IBS longer than 6months were compared with
      healthy matched controls (n=12). Peripheral whole blood from fasting participants
      was collected and RNA was extracted. The expression of 96 inflammatory genes was
      then analyzed using a custom quantitative real-time PCR array. KEY RESULTS: CCL
      16 gene expression was upregulated by 7.46-fold in IBS patients when compared
      with controls. CCL-16 was overexpressed by over 130-fold in IBS-constipation
      patients when compared with both controls and IBS-diarrhea patients. CONCLUSIONS
      & INFERENCES: These results further suggest a subclinical inflammatory component
      underlying IBS. To better understand the phenotypic differences in IBS it is
      important to broaden the study of these inflammatory and other biomarkers.

PMID- 21951811
TI  - Behavioural phenotypes: from models to intervention.

PMID- 21951810
TI  - Reference genes for gene expression studies in wheat flag leaves grown under
      different farming conditions.
AB  - BACKGROUND: Internal control genes with highly uniform expression throughout the
      experimental conditions are required for accurate gene expression analysis as no
      universal reference genes exists. In this study, the expression stability of 24
      candidate genes from Triticum aestivum cv. Cubus flag leaves grown under organic
      and conventional farming systems was evaluated in two locations in order to
      select suitable genes that can be used for normalization of real-time
      quantitative reverse-transcription PCR (RT-qPCR) reactions. The genes were
      selected among the most common used reference genes as well as genes encoding
      proteins involved in several metabolic pathways. FINDINGS: Individual genes
      displayed different expression rates across all samples assayed. Applying geNorm,
      a set of three potential reference genes were suitable for normalization of RT
      qPCR reactions in winter wheat flag leaves cv. Cubus: TaFNRII (ferredoxin-NADP(H)
      oxidoreductase; AJ457980.1), ACT2 (actin 2; TC234027), and rrn26 (a putative
      homologue to RNA 26S gene; AL827977.1). In addition of these three genes that
      were also top-ranked by NormFinder, two extra genes: CYP18-2 (Cyclophilin A,
      AY456122.1) and TaWIN1 (14-3-3 like protein, AB042193) were most consistently
      stably expressed.Furthermore, we showed that TaFNRII, ACT2, and CYP18-2 are
      suitable for gene expression normalization in other two winter wheat varieties
      (Tommi and Centenaire) grown under three treatments (organic, conventional and no
      nitrogen) and a different environment than the one tested with cv. Cubus.
      CONCLUSIONS: This study provides a new set of reference genes which should
      improve the accuracy of gene expression analyses when using wheat flag leaves as
      those related to the improvement of nitrogen use efficiency for cereal
      production.

PMID- 21951813
TI  - ACORNS: a tool for the visualisation and modelling of atypical development.
AB  - Across many academic disciplines visualisation and notation systems are used for
      modelling data and developing theory, but in child development visual models are
      not widely used; yet researchers and students of developmental difficulties may
      benefit from a visualisation and notation system which can clearly map
      developmental outcomes and trajectories, and convey hypothesised dynamic causal
      pathways. Such a system may help understanding of existing accounts and be a tool
      for developing new theories. We first present criteria that need to be met in
      order to provide fully nuanced visualisations of development, and discuss
      strengths and weaknesses of the visualisation system proposed by Morton.
      Secondly, we present a tool we have designed to give more precise accounts of
      development while also being accessible, intuitive and visually appealing. We
      have called this an Accessible Cause-Outcome Representation and Notation System
      (ACORNS). This system provides a framework for clear mapping and modelling of
      developmental sequences, illustrating more precisely how functions change over
      time, how factors interact with the environment, and the absolute and relative
      nature of causal outcomes. We provide a new template, a set of rules for the
      appropriate use of boxes and arrows, and a set of visually accessible indicators
      that can be used to show more precisely relative rates, degrees and variance of
      functioning over different capacities at different time points. We have designed
      ACORNS to give a precise and clear visualisation of how development unfolds;
      allowing the representation of less 'static' and more transactional models of
      developmental difficulties. We hope ACORNS will help students, clinicians and
      theoreticians across disciplines to better represent nuances of debates, and be a
      seed for the development of new theory.

PMID- 21951814
TI  - The N-terminal beta-barrel domain of mammalian lipoxygenases including mouse 5
      lipoxygenase is not essential for catalytic activity and membrane binding but
      exhibits regulatory functions.
AB  - Mammalian lipoxygenases (LOXs) have been implicated in cell differentiation and
      in the pathogenesis of inflammatory and hyperproliferative diseases. The
      available structural information indicated that lipoxygenases constitute single
      polypeptide chain enzymes consisting of a small N-terminal beta-barrel domain and
      a larger C-terminal subunit that harbors the catalytic non-heme iron. Because of
      its structural similarity to C2-domains of lipases the N-terminal beta-barrel
      domain of lipoxygenases, which comprises about 110 amino acids, has been
      implicated in membrane binding and activity regulation. To explore the functional
      relevance of the C2-domain in more detail and to develop a more comprehensive
      hypothesis on the biological role of this structural subunit we performed gene
      technical truncation on various mammalian LOX isoforms (12/15-LOXs of various
      species, human 15-LOX2, mouse 5-LOX) and quantified catalytic activity and
      membrane binding properties of the truncated recombinant enzyme species. We found
      that the C2-domain is not essential for catalytic activity and does hardly impact
      reaction specificity. Truncated enzyme species exhibit impaired membrane binding
      properties and altered reaction kinetics. Taken together, our data suggests a
      regulatory importance of the N-terminal beta-barrel domain for mammalian
      lipoxygenase isoforms.

PMID- 21951815
TI  - Ribonucleotide reductase inhibition by p-alkoxyphenols studied by molecular
      docking and molecular dynamics simulations.
AB  - Ribonucleotide reductase (RNR) is necessary for production of the precursor
      deoxyribonucleotides for DNA synthesis. Class Ia RNR functions via a stable free
      radical in one of the two components protein R2. The enzyme mechanism involves
      long range (proton coupled) electron transfer between protein R1 and the tyrosyl
      radical in protein R2. Earlier experimental studies showed that p-alkoxyphenols
      inhibit RNR. Here, molecular docking and molecular dynamics simulations involving
      protein R2 suggest an inhibition mechanism for p-alkoxyphenols . A low energy
      binding pocket is identified in protein R2. The preferred configuration provides
      a structural basis explaining their specific binding to the Escherichia coli and
      mouse R2 proteins. Trp48 (E. coli numbering), on the electron transfer pathway,
      is involved in the interactions with the inhibitors. The relative order of the
      binding energies calculated for the phenol derivatives to protein R2 is
      correlated with earlier experimental data on inhibition efficiency, in turn
      related to increasing size of the hydrophobic alkyl substituents. Using the
      configuration identified by molecular docking as a starting point for molecular
      dynamics simulations, we find that the p-allyloxyphenol interrupts the catalytic
      electron transfer pathway of the R2 protein by forming hydrogen bonds with Trp48
      and Asp237, thus explaining the inhibitory activity of p-alkoxyphenols.

PMID- 21951816
TI  - Infantile bromoderma due to antiepileptic therapy.

PMID- 21951817
TI  - Relational grounding facilitates development of scientifically useful multiscale
      models.
AB  - We review grounding issues that influence the scientific usefulness of any
      biomedical multiscale model (MSM). Groundings are the collection of units,
      dimensions, and/or objects to which a variable or model constituent refers. To
      date, models that primarily use continuous mathematics rely heavily on absolute
      grounding, whereas those that primarily use discrete software paradigms (e.g.,
      object-oriented, agent-based, actor) typically employ relational grounding. We
      review grounding issues and identify strategies to address them. We maintain that
      grounding issues should be addressed at the start of any MSM project and should
      be reevaluated throughout the model development process. We make the following
      points. Grounding decisions influence model flexibility, adaptability, and thus
      reusability. Grounding choices should be influenced by measures, uncertainty,
      system information, and the nature of available validation data. Absolute
      grounding complicates the process of combining models to form larger models
      unless all are grounded absolutely. Relational grounding facilitates referent
      knowledge embodiment within computational mechanisms but requires separate model
      to-referent mappings. Absolute grounding can simplify integration by forcing
      common units and, hence, a common integration target, but context change may
      require model reengineering. Relational grounding enables synthesis of large,
      composite (multi-module) models that can be robust to context changes. Because
      biological components have varying degrees of autonomy, corresponding components
      in MSMs need to do the same. Relational grounding facilitates achieving such
      autonomy. Biomimetic analogues designed to facilitate translational research and
      development must have long lifecycles. Exploring mechanisms of normal-to-disease
      transition requires model components that are grounded relationally. Multi
      paradigm modeling requires both hyperspatial and relational grounding.

PMID- 21951818
TI  - Multimodal therapy as an algorithm to limb salvage in diabetic patients with
      large heel ulcers.
AB  - In many series of diabetic foot ulcer care, heel ulcers greater than 4 cm across
      have been identified as an independent predictor of limb loss. Therefore, we set
      out to pursue the most aggressive limb salvage algorithm in patients with heel
      ulcers greater than 4 cm in diameter. Over 5 years, we identified 21 patients, 39
      84 years of age, all with diabetes mellitus, with heel ulcers greater than 4 cm
      in diameter and had magnetic resonance imaging or bone scan evidence of
      osteomyelitis. Seven of the 21 patients had end-stage renal disease defined as
      being haemodialysis dependent. All patients had ankle brachial indices <0.4 or
      monophasic pulse volume recordings. All patients underwent distal bypass surgery
      with vein. After adequate perfusion was obtained, all patients underwent partial
      calcanectomy and intra-operative negative pressure wound therapy (NPWT)
      placement. This was followed by treatment with recombinant platelet-derived
      growth factor (PDGF). One patient underwent amputation during the healing process
      secondary to ongoing sepsis. Twenty of 21 patients healed acutely (within 6
      months). Three of 20 patients went on to subsequent below knee amputation within
      12 months of healing primarily. At 2 years, 12 of 21 (57%) were ambulating
      independently, 1 of 21 was dead, 4 of 21 had undergone amputation, 4 (19%) had
      limbs that were intact but were not ambulating. A total limb salvage rate of 76%
      at 2 years mirrored the secondary patency rates, with 100% follow up. Heel ulcers
      require multimodality therapy if they are going to have any chance to heal. We
      believe the algorithm presented allows for the required revascularisation and a
      modulation of the heel ulcer microenvironment by augmenting the microcirculation
      through NPWT, and improving the proliferative capacity with PDGF.

PMID- 21951819
TI  - Immune response of 23-valent pneumococcal polysaccharide vaccinated elderly and
      its relation to frailty indices, nutritional status, and serum zinc levels.
AB  - AIM: To detect the immunoglobulin M memory B cell population response following
      vaccination with the 23-valent pneumococcal polysaccharide vaccine and determine
      its relation to frailty indices, nutritional status, and serum zinc levels.
      METHODS: A cross-sectional study was carried out in the outpatient geriatric
      clinic, Ain Shams University Hospital. It included 80 community-dwelling elderly,
      32 male and 48 female. Each participant underwent vaccination with the 23-valent
      pneumococcal polysaccharide vaccine, comprehensive geriatric assessment,
      nutritional assessment with the DETERMINE check list, frailty indices assessment,
      and serum zinc level measurement. The percentage of immunoglobulin M memory B
      cells was evaluated before and 4 weeks after vaccination. Immune response was
      calculated as the difference between cell percentage before and after
      vaccination. RESULTS: Before the vaccination, the immunoglobulin M memory B cell
      percentage was significantly lower among those eating fewer than two meals a day
      and taking three or more drugs a day; after vaccination significance was observed
      among those with tooth or mouth problems that make eating difficult. Immune
      response was significantly lower among those with tooth or mouth problems (P <
      0.001), weight loss (P < 0.001), shrinking (P = 0.001), poor endurance (P =
      0.04), multiple comorbidities (P = 0.013), and cognitive impairment (P = 0.001).
      Participants with immune response >=10% showed significantly higher serum zinc
      levels compared to those with immune response <10% of increase in cell
      percentage. CONCLUSION: Poor nutritional status, frailty and a lower zinc level
      impair the immunological response of elderly individuals.

PMID- 21951821
TI  - Esophageal spasm: demographic, clinical, radiographic, and manometric features in
      108 patients.
AB  - Diffuse esophageal spasm (DES) remains insufficiently understood. Here we aimed
      to summarize the demographic, clinical, radiographic, and manometric features in
      a large cohort of patients with DES. We identified all consecutive patients
      diagnosed with DES from 2000 to 2006 at Mayo Clinic Florida. The computerized
      records of these patients were reviewed to extract relevant information. We
      performed 2654 esophageal motilities during that period. There were 108 patients
      with esophageal spasm, and 55% were female. Median age was 71 years. The most
      common leading symptom was dysphagia in 55, followed by chest pain in 31. Weight
      loss occurred in 28 patients. The median of time from onset of symptoms to
      diagnosis was 48 months (range 0-480), with a median of time from the first
      medical consultation to diagnosis of 8 months (range 0-300). The most frequent
      comorbidities were hypertension and psychiatric problems. At presentation, 81
      patients were taking acid-reducing medications, and 49 patients were taking
      psychotropic drugs. An abnormal esophagogram was noted in 46 of 76 patients with
      this test available, but most radiographic findings were nonspecific with the
      typical 'corkscrew' appearance seen in only three patients. Gastroesophageal
      reflux disease (GERD) was diagnosed by pH testing or endoscopy in 41 patients. We
      did not find any difference between the rate of simultaneous contractions or
      esophageal amplitude between patients with a leading symptom of dysphagia and
      those with chest pain. DES is an uncommon motility disorder that often goes
      unrecognized for years. Physicians should be aware of the clinical heterogeneity
      of DES and consider motility testing early in the course of unexplained
      esophageal symptoms. Given the high prevalence of GERD in DES, the role of GERD
      and the impact of acid-reducing therapy in DES deserve further study.

PMID- 21951822
TI  - Early prophylaxis/FVIII tolerization regimen that avoids immunological danger
      signals is still effective in minimizing FVIII inhibitor developments in
      previously untreated patients--long-term follow-up and continuing experience.

PMID- 21951823
TI  - Actions taken by young people to deal with mental disorders: findings from an
      Australian national survey of youth.
AB  - AIMS: The study examined actions taken by young people to deal with mental
      disorders and the factors associated with help-seeking and self-help behaviours.
      METHODS: Participants in a 2006 national survey of Australian youth (aged 12-25
      years) were contacted 2 years later and participated in telephone interviews
      based on a vignette of one of the following disorders: depression, depression
      with alcohol misuse, social phobia and psychosis. Personal experiences of these
      disorders and subsequent self-help and help-seeking behaviours were examined.
      RESULTS: Of the 2005 participants interviewed, 275 (14%) reported experiencing a
      mental disorder since January 2007, most commonly depression. The most frequent
      sources of help were family (77%) and close friends (73%). General practitioners
      (GPs) were consulted by 53% of respondents. The most frequent self-help
      behaviours were physical activity (70%) and getting up early and out in the
      sunlight (46%). Beliefs about the helpfulness of interventions at baseline were
      compared with actual use in the following 2 years. Interventions ranked higher
      for beliefs about helpfulness than actual use mainly included consulting health
      professionals and cutting down on substance use. Interventions ranked higher for
      actual use than beliefs typically included lifestyle interventions but also
      included consulting GPs. CONCLUSIONS: Young people with mental health problems
      are more likely to seek help from close friends and family and to use self-help
      interventions than to access professional help, although over half of survey
      respondents had visited a GP. Help seeking tended to be better predicted by
      intentions to seek help than by beliefs about the helpfulness of interventions.

PMID- 21951824
TI  - Economic impact of potential drug-drug interactions among osteoarthritis patients
      taking opioids.
AB  - Patients with osteoarthritis (OA) taking at least one CYP450-metabolized opioid
      concurrently with another CYP450-metabolized medication experience a drug-drug
      exposure (DDE), which puts them at risk of a pharmacokinetic drug-drug
      interaction (PK DDI). This study compared patients with and without such an
      incident DDE to determine healthcare utilization and associated payments. Using a
      retrospective database analysis, the impact of DDEs was evaluated in terms of
      associated clinical events, healthcare services utilization (office visits,
      outpatient visits, ED visits, hospitalization), and payments in patient
      populations based on age (those under age 65 and those 65 years of age and
      older), during the 6 months after exposure. DDE patients had significantly more
      inpatient hospitalizations than no-DDE patients. Mean total payments at 6 months
      were significantly higher for both younger and older patients with DDE compared
      to similar patients without DDE ($9,469, SD = $12,192 vs. $8,382, SD = $14,078,
      respectively, for younger patients, resulting in a difference of $1,087, P <
      0.004, and $9,829, SD = $11,721 vs. $8,622, SD = $10,131, respectively, for older
      patients, resulting in a difference of $1,207, P = 0.001). In both age groups,
      DDE patients had significantly higher payments for nonopioid prescription drugs
      ($1,824 SD = $2,420 vs. $1,362, SD = $1,891, respectively, for younger patients,
      resulting in a difference of $462, P < 0.001, and $2,197 SD = $2,332 vs. $2,013,
      SD = $2,437, respectively, for older patients, resulting in a difference of $184,
      P = 0.020). Overall, patients with OA who experienced DDEs had significantly
      greater utilization rates of healthcare resources and higher associated payments
      in the 6-month observation period following the exposure, compared to patients
      without DDEs, consistent with the risk of PK DDIs associated with DDEs.

PMID- 21951825
TI  - Incidence and outcome of first syncope in primary care: A retrospective cohort
      study.
AB  - ABSTRACT:  BACKGROUND: Assessment of risk for serious cardiovascular outcome
      after syncope is difficult. OBJECTIVES: To determine the incidence of first
      syncope in primary care. To investigate the relation between syncope and serious
      cardiovascular (CV) outcome and serious injury. METHODS: Retrospective cohort
      study using data from the Intego general practice-based registration network,
      collecting data from 55 general practices (90 GP's). All patients with a first
      syncope from 1994 to 2008 were included; five participants without syncope were
      matched for age and gender for every patient with syncope. The main outcome
      measures were incidence of first syncope by age and gender and one year risk of
      serious CV outcome or injury after syncope. RESULTS: 2785 patients with syncope
      and 13909 matched patients without syncope were included. The overall incidence
      of a first syncope was 1.91 per 1000 person-years (95% CI 1.83-1.98). The
      incidence was higher in females (2.42 (95% CI 2.32-2.55) per 1000 person-years)
      compared to males (1.4 (95% CI 1.32-1.49) per 1000 person-years) and follows a
      biphasic pattern according to age: a first peak at the age of 15-24 years is
      followed by a sharp rise above the age of 45. One year serious outcome after
      syncope was recorded in 12.3% of patients. Increasing age (HR 1.04 (1.03-1.04)),
      CV comorbidity (HR 3.48 (95% CI 2.48-4.90) and CV risk factors (HR 1.65 (95% CI
      1.24-2.18) are associated with serious outcome. Cox regression, adjusting for
      age, gender, CV comorbidity and risk factors, showed that syncope was an
      independent risk factor for serious CV outcome or injury (HR 3.99 (95% CI 3.44
      4.63)). The other independent risk factors were CV comorbidity (HR 1.81 (95% CI
      1.51-2.17)) and age (HR 1.03 (95% CI 1.03-1.04)). CONCLUSIONS: Incidence rate of
      first syncope in primary care was 1.91 per 1000 person-years. One year risk of
      serious outcome after syncope was 12.3%. Increasing age, CV comorbidity and risk
      factors are associated with serious outcome. Compared to a control group, syncope
      on itself is an independent risk factor for serious outcome (adjusted for age,
      gender, CV comorbidity and risk factors).

PMID- 21951826
TI  - Trends in the use of of nephron-sparing surgery (NSS) at an Australian tertiary
      referral centre: an analysis of surgical decision-making using the R.E.N.A.L.
      nephrometry scoring system.
AB  - Study Type--Therapy (case series). Level of Evidence 4. What's known on the
      subject? And what does the study add? Nephron-sparing surgery (NSS) is
      increasingly recognised as a preferred form of management for the incidentally
      detected small renal mass (SRM). Within the context of equivalent oncological
      outcomes, patients treated by NSS may have a survival advantage over those
      treated by radical nephrectomy (RN) through a reduced risk of chronic kidney
      disease and its associated cardiac morbidity. Despite this, according to Medicare
      data from the USA, a disproportionate number of patients with SRMs continue to be
      treated with RN instead of NSS. Similar data from Australia are not yet
      available. The present study explores the evolving management of SRMs at an
      Australian tertiary centre over a 5-year period. It utilises the R.E.N.A.L.
      Nephrometry Score to assess how lesion complexity has influenced surgical
      decision-making and charts the increasing use of NSS in the management of low
      complexity renal masses at our centre. OBJECTIVE: * To examine recent trends in
      the use of nephron-sparing surgery (NSS) at our centre. Specifically, we sought
      to examine the process of surgical decision-making by applying the R.E.N.A.L.
      nephrometry scoring system to assess the complexity of lesions for which surgery
      was undertaken. PATIENTS AND METHODS: * We performed a retrospective review of
      renal masses treated by surgery from January 2005 to December 2009, including 79
      RN and 70 NSS. * CT images were available for analysis in 50 patients within each
      group. * Lesions were scored on the basis of their complexity using the
      R.E.N.A.L. nephrometry scoring system developed by Kutikov and Uzzo. RESULTS: *
      There was no difference in age between patients undergoing RN and NSS (median age
      61 vs 60 years). * RN was performed for significantly larger lesions (mean [sd]
      68 [9] vs 29 [2] mm, P < 0.05) of predominantly moderate and high complexity (12%
      low, 56% moderate, 32% high). * NSS was primarily used for low-complexity
      lesions, but included four (8%) moderate-complexity lesions in the final 2 years
      of the study. * The use of NSS increased from 28.6% of cases in 2005 to 60.0% of
      cases in 2009, which mirrored the increase in the proportion of operations
      performed for low-complexity lesions (22.2% low-complexity in 2005 to 70.6% in
      2009, P < 0.01 for trend). CONCLUSIONS: * The increasing use of NSS at our
      institution mirrored the increasing treatment of low-complexity renal lesions. *
      This may reflect an increased detection and referral of such lesions, or a shift
      towards treatment of lesions that in the past would have been under surveillance.
      * Practice at our centre reflects a shifting paradigm towards preferential use of
      NSS for the treatment of suitable renal masses.

PMID- 21951829
TI  - Mimicking GEFs: a common theme for bacterial pathogens.
AB  - Small molecular weight GTPases are master regulators of eukaryotic signalling,
      making them prime targets for bacterial virulence factors. Here, we review the
      recent advances made in understanding how bacterial type III secreted effector
      proteins directly activate GTPase signalling cascades. Specifically we focus on
      the SopE/WxxxE family of effectors that functionally mimic guanine nucleotide
      exchange factors (GEFs): the endogenous activators of Rho-family GTPases. Recent
      structural and biochemical studies have provided keen insight into both the
      signalling potency and substrate specificity of bacterial GEFs. Additionally,
      these bacterial GEFs display fascinating cell biological properties that provide
      insight into both host cell physiology and infectious disease strategies.

PMID- 21951830
TI  - Clinicians adopting evidence based guidelines: a case study with
      thromboprophylaxis.
AB  - BACKGROUND: Venous Thromboembolism (VTE) is a cause of hospital mortality and
      managing its morbidity is associated with significant expenditure. Uptake of
      evidenced based guideline recommendations intended to prevent VTE in hospital
      settings is sub-optimal. This study was conducted to explore clinicians'
      attitudes and the clinical environment in which they work to understand their
      reluctance to adopt VTE prophylaxis guidelines. METHODS: Between February and
      November 2009, 40 hospital employed doctors from 2 Australian metropolitan
      hospitals were interviewed in depth. Qualitative data were analysed according to
      thematic methodology. RESULTS: Analysis of interviews revealed that barriers to
      evidence based practice include i) the fragmented system of care delivery where
      multiple members of teams and multiple teams are responsible for each patient's
      care, and in the case of VTE, where everyone shares responsibility and no-one in
      particular is responsible; ii) the culture of practice where team practice is
      tailored to that of the team head, and where medicine is considered an 'art' in
      which guidelines should be adapted to each patient rather than applied
      universally. Interviewees recommend clear allocation of responsibility and
      reminders to counteract VTE risk assessment being overlooked. CONCLUSIONS: Senior
      clinicians are the key enablers for practice change. They will need to be
      convinced that guideline compliance adds value to their patient care. Then with
      the support of systems in the organisation designed to minimize the effects of
      care fragmentation, they will drive practice changes in their teams. We believe
      that evidence based practice is only possible with a coordinated program that
      addresses individual, cultural and organisational constraints.

PMID- 21951831
TI  - Preliminary evidence of an association between the functional c-kit rs6554199
      polymorphism and achalasia in a Turkish population.
AB  - BACKGROUND: C-kit-positive interstitial cells of Cajal (ICC) of the lower
      esophageal sphincter are reduced in achalasia. Two functional gene polymorphisms
      (rs2237025 and rs6554199) within the c-kit gene may affect its transcriptional
      activity. In this pilot study, we hypothesized that these polymorphisms would be
      associated with achalasia. METHODS: Genomic DNA was extracted and real-time PCR
      reactions were used to determine the rs2237025 and rs6554199 c-kit polymorphisms
      in 88 Turkish patients with achalasia and 101 healthy controls. KEY RESULTS: The
      frequency of the T allele of rs6554199 was significantly higher in patients with
      achalasia [odds ratio (OR): 1.55; 95% confidence interval (CI), 1.03-2.34; P =
      0.038] compared with the G allele. Under a dominant model of inheritance, the
      carriage of at least one T allele was significantly more frequent in patients
      with achalasia (80.7%) than in controls (65.3%; OR: 2.21; 95% CI, 1.13-4.33; P =
      0.022). No association of the c-kit rs2237025 polymorphism with achalasia was
      detected. CONCLUSIONS & INFERENCES: Despite the small sample size and the
      possibility of a false positive finding, our preliminary data support the
      hypothesis that the T allele of the c-kit rs6554199 polymorphism may be
      associated with achalasia in the Turkish population. These findings need to be
      replicated in other racial-ethnically diverse populations.

PMID- 21951832
TI  - The incidence of hypoglycaemia in Muslim patients with type 2 diabetes treated
      with sitagliptin or a sulphonylurea during Ramadan: a randomised trial.
AB  - AIMS: To compare the incidence of symptomatic hypoglycaemia in fasting Muslim
      patients with type 2 diabetes treated with sitagliptin or a sulphonylurea during
      Ramadan. METHODS: Patients with type 2 diabetes (age >= 18 years) who were
      treated with a stable dose of a sulphonylurea with or without metformin for at
      least 3 months prior to screening, who had an HbA(1c) < 10% and who expressed
      their intention to daytime fast during Ramadan were eligible for this open-label
      study. Patients were randomised in a 1 : 1 ratio to either switch to sitagliptin
      100 mg qd or to remain on their prestudy sulphonylurea. Patients completed daily
      diary cards to document information on hypoglycaemic symptoms and complications.
      The primary end-point was the overall incidence of symptomatic hypoglycaemia
      recorded during Ramadan. RESULTS: Of the 1066 patients randomised, 1021 (n = 507
      for sitagliptin and n = 514 for sulphonylurea) returned at least one completed
      diary card and were included in the analysis. The proportion of patients who
      recorded one or more symptomatic hypoglycaemic events during Ramadan was lower in
      the sitagliptin group (6.7%) compared with the sulphonylurea group (13.2%). The
      risk of symptomatic hypoglycaemia was significantly decreased with sitagliptin
      relative to sulphonylurea treatment (Mantel-Haenszel relative risk ratio [95% CI]
      = 0.51 [0.34, 0.75]; p < 0.001). There were no reported events that required
      medical assistance (i.e. visits to physician or emergency room or
      hospitalisations) or were considered severe (i.e. events that caused loss of
      consciousness, seizure, coma or physical injury) during Ramadan. CONCLUSIONS: In
      Muslim patients with type 2 diabetes who observed the fast during Ramadan,
      switching to a sitagliptin-based regimen decreased the risk of hypoglycaemia
      compared with remaining on a sulphonylurea-based regimen. The incidence of
      hypoglycaemia was lower with gliclazide relative to the other sulphonylurea
      agents and similar to that observed with sitagliptin.

PMID- 21951833
TI  - The efficacy of optic nerve ultrasonography for differentiating papilloedema from
      pseudopapilloedema in eyes with swollen optic discs.
AB  - PURPOSE: To evaluate the diagnostic yield of optic nerve ultrasonography (US) in
      distinguishing between papilloedema (swollen discs owing to raised intracranial
      pressure) and pseudopapilloedema. METHODS: We prospectively evaluated all
      patients with bilateral optic disc swelling who underwent a complete neuro
      ophthalmological examination. Suitable patients were referred for neuroimaging
      (computerized tomography or magnetic resonance imaging) and lumbar puncture. They
      underwent optic nerve US (A-mode and B-mode), and the findings were compared with
      the final clinical assessment. Sensitivity, specificity and predictive values for
      US distinction between true papilloedema and pseudopapilloedema were calculated
      and compared with those of the other imaging tests. RESULTS: Forty-four patients
      were enrolled. Ultrasonography detected papilloedema with a high degree of
      sensitivity (85%) when the normal optic nerve width (ONW) was set at <=3.3 mm,
      and with an even higher degree of sensitivity (95%) when the normal ONW was set
      at <=3.0 mm. Ultrasonography had a high negative predictive value for detecting
      papilloedema: 83% when the normal ONW was set at <=3.3 mm and 93% when it was set
      at <=3.0 mm. There was a significant correlation between the US findings and the
      final diagnosis (p < 0.001) when the upper limit of the normal ONW was set at 3.0
      mm. CONCLUSIONS: Ultrasonography findings of the ONW correlated well with the
      final diagnosis of papilloedema or pseudopapilloedema, especially when the upper
      limit of the normal ONW was set at 3.0 mm. Ultrasonography could be a useful non
      invasive technique for differentiating papilloedema from other causes for swollen
      discs, such as pseudopapilloedema.

PMID- 21951835
TI  - Prevalence of Korean cats with natural feline coronavirus infections.
AB  - BACKGROUND: Feline coronavirus is comprised of two pathogenic biotypes consisting
      of feline infectious peritonitis virus (FIPV) and feline enteric coronavirus
      (FECV), which are both divided into two serotypes. To examine the prevalence of
      Korean cats infected with feline coronavirus (FCoV) type I and II, fecal samples
      were obtained from 212 cats (107 pet and 105 feral) in 2009. RESULTS: Fourteen
      cats were FCoV-positive, including infections with type I FCoV (n = 8), type II
      FCoV (n = 4), and types I and II co-infection (n = 2). Low seroprevalences
      (13.7%, 29/212) of FCoV were identified in chronically ill cats (19.3%, 16/83)
      and healthy cats (10.1%, 13/129). CONCLUSIONS: Although the prevalence of FCoV
      infection was not high in comparison to other countries, there was a higher
      prevalence of type I FCoV in Korean felines. The prevalence of FCoV antigen and
      antibody in Korean cats are expected to gradually increase due to the rising
      numbers of stray and companion cats.

PMID- 21951836
TI  - Engaging rural preceptors in new longitudinal community clerkships during
      workforce shortage: a qualitative study.
AB  - BACKGROUND: In keeping with its mission to produce doctors for rural and regional
      Australia, the University of Wollongong, Graduate School of Medicine has
      established an innovative model of clinical education. This includes a 12-month
      integrated community-based clerkship in a regional or rural setting, offering
      senior students longitudinal participation in a 'community of practice' with
      access to continuity of patient care experiences, continuity of supervision and
      curriculum, and individualised personal and professional development. This
      required developing new teaching sites, based on attracting preceptors and
      providing them with educational and physical infrastructure. A major challenge
      was severe health workforce shortages. METHODS: Before the new clerkship started,
      we interviewed 28 general practitioners to determine why they engaged as
      clerkship preceptors. Independent researchers conducted semi-structured
      interviews. Responses were transcribed for inductive qualitative content
      analysis. RESULTS: The new model motivated preceptors to engage because it
      enhanced their opportunities to contribute to authentic learning when compared
      with the perceived limitations of short-term attachments. Preceptors appreciated
      the significant recognition of the value of general practice teaching and the
      honour of major involvement in the university. They predicted that the initiative
      would have positive effects on general practitioner morale and improve the
      quality of their practice. Other themes included the doctors' commitment to their
      profession, 'handing on' to the next generation and helping their community to
      attract doctors in the future. CONCLUSIONS: Supervisors perceive that new models
      of clinical education offer alternative solutions to health care education,
      delivery and workforce. The longitudinal relationship between preceptor, student
      and community was seen as offering reciprocal benefits. General practitioners are
      committed to refining practice and ensuring generation of new members in their
      profession. They are motivated to engage in novel regional and rural longitudinal
      clinical clerkships as they perceive that they offer students an authentic
      learning experience and are a potential strategy to help address workforce
      shortages and maldistribution.

PMID- 21951834
TI  - Implication of haematophagous arthropod salivary proteins in host-vector
      interactions.
AB  - The saliva of haematophagous arthropods contains an array of anti-haemostatic,
      anti-inflammatory and immunomodulatory molecules that contribute to the success
      of the blood meal. The saliva of haematophagous arthropods is also involved in
      the transmission and the establishment of pathogens in the host and in allergic
      responses. This survey provides a comprehensive overview of the pharmacological
      activity and immunogenic properties of the main salivary proteins characterised
      in various haematophagous arthropod species. The potential biological and
      epidemiological applications of these immunogenic salivary molecules will be
      discussed with an emphasis on their use as biomarkers of exposure to
      haematophagous arthropod bites or vaccine candidates that are liable to improve
      host protection against vector-borne diseases.

PMID- 21951837
TI  - Comparison of the diagnostic value of 3-deoxy-3-18F-fluorothymidine and 18F
      fluorodeoxyglucose positron emission tomography/computed tomography in the
      assessment of regional lymph node in thoracic esophageal squamous cell carcinoma:
      a pilot study.
AB  - We used pathological examination as golden standard to determine whether 3-deoxy
      3-(18)F-fluorothymidine positron emission tomography/computed tomography (FLT
      PET/CT) can detect regional lymph node metastasis in untreated thoracic
      esophageal squamous cell carcinoma and additionally performed (18)F
      fluorodeoxyglucose (FDG) PET/CT for direct comparison with that of FLT. Twenty
      two patients with thoracic esophageal squamous cell carcinoma underwent dual
      tracer PET/CT examinations before surgery. The results of reviewing CT images and
      side-by-side FDG PET and FLT PET images for the diagnosis of locoregional lymph
      node metastasis were compared prospectively in relation to pathologic findings.
      All patients underwent esophagectomy and lymphadenectomy. Pathologic examination
      confirmed nodes positive for metastasis in 16 patients and 47 of 424 excised
      nodes. The uptake of FDG (median SUVmax, 5.4; range, 2.4-10.6) in locoregional
      lymph nodes metastases was significantly higher than that of FLT (median SUVmax,
      2.8; range, 1.3-4.6). There were 14 false-positive nodes in FDG PET/CT and only 3
      in FLT PET/CT; 8 false-negative nodes in FDG PET/CT, while there were 12 false
      negative nodes in FLT PET/CT. The sensitivity, specificity, accuracy, positive
      predictive value, and negative predictive value of FLT PET/CT were 74.47%,
      99.20%, 96.46%, 92.11%, and 96.89%, respectively, whereas those of FDG PET/CT
      were 82.98%, 96.29%, 94.81%, 82.98%, and 96.29%, respectively. P-values were
      0.450, 0.014, 0.313, 0.050, and 0.555, respectively. FLT uptake in regional lymph
      nodes of esophageal carcinoma is significantly lower compared with FDG uptake.
      FLT PET/CT has fewer false-positive findings and higher specificity compared with
      FDG PET/CT.

PMID- 21951838
TI  - Clinician views of referring people with negative symptoms to outcome research: a
      questionnaire survey.
AB  - This paper reports on a survey of mental health clinician views of including
      people with psychosis and negative symptoms in outcome research. A questionnaire
      was forwarded to clinicians (the majority of whom were mental health nurses)
      completing post-registration undergraduate and postgraduate degree courses in
      psychosocial interventions for psychosis. Fifty questionnaires were returned (a
      response rate of 84.7%). A total of 47% of respondents indicated that they might
      refrain from offering this group as potential participants to clinical trials.
      Thematic analysis suggests views that negative symptoms are not amenable to
      treatment inform such decisions. The results highlight the potential difficulties
      faced by researchers investigating new treatments for people with negative
      symptoms, and suggest further exploration of clinician views of referring this
      group to research and psychosocial treatments is warranted.

PMID- 21951839
TI  - Actions taken to deal with mental health problems in Australian higher education
      students.
AB  - AIMS: With approximately 50% of young people aged 18-24 in tertiary education,
      these are potential settings for programmes to improve mental health literacy. A
      survey was carried out with students and staff of a tertiary education
      institution to investigate psychological distress, actions to deal with mental
      health problems and first-aid behaviours. METHODS: Telephone interviews were
      carried out with 774 students of an Australian metropolitan university (with 422
      staff as a comparison group). They answered questions relating to psychological
      distress, actions to deal with mental health problems and first-aid behaviours.
      RESULTS: Students were more likely to be psychologically distressed than staff
      (21% vs. 13%) and 27% reported experiencing a problem similar to that described
      in a depression vignette. The most common actions taken were talking to a close
      friend, physical activity and talking to close family. Over 72% of students with
      a problem had sought professional help, most often from a general practitioner or
      counsellor. Only 10% reported seeking help from a student counsellor. Helpful
      first-aid behaviours were common and were seen in over 90% of students who had a
      family member or close friend with a similar problem. CONCLUSIONS: There is a
      need for further investigation of levels and factors associated with
      psychological distress in higher education students along with an exploration of
      barriers to and enablers of use of student counselling services. High levels of
      help seeking from friends and first-aid behaviours provided point to the need for
      effective peer-to-peer education.

PMID- 21951841
TI  - The role of surgery in high-risk localised prostate cancer.
AB  - * The optimal management of high-risk localised prostate cancer is a major
      challenge for urologists and oncologists. It is clear that multimodal therapy
      including radical local treatment is needed in these men to achieve the best
      outcomes. * External beam radiotherapy (EBRT) is an essential component of
      therapy either as a primary or adjuvant treatment. However, the role of radical
      prostatectomy (RP) is more controversial. Both methods are currently valid
      therapy options. * There have been many individual studies of EBRT and RP in high
      risk disease, but no good quality large prospective randomized trials. * In EBRT,
      combination with neoadjuvant plus long-term adjuvant androgen-deprivation therapy
      (ADT) has been conclusively shown to improve outcomes and is widely considered
      the standard of care. * However, the role of RP has achieved recent prominence
      with several important studies. Published data from prospective randomized trials
      in patients after RP have shown that in men with adverse pathological features at
      surgery, the addition of adjuvant RT improves biochemical-free and progression
      free survival. * More recently, studies from large-volume centres comparing EBRT
      and RP have provided intriguing suggestions of better outcomes with RP as the
      primary treatment. * An important question therefore, is which of the two methods
      provides the best outcome in men with localised high-risk disease. Crucially,
      does the combination of RP and selective adjuvant EBRT provide clinically
      significant better outcomes compared with EBRT alone? * In this review we discuss
      the current evidence for the role of RP for high-risk localised prostate cancer
      and define the parameters and urgent need for a prospective trial to test the
      role of surgery for this group of patients.

PMID- 21951842
TI  - Rice homeobox transcription factor HOX1a positively regulates gibberellin
      responses by directly suppressing EL1.
AB  - Homeobox transcription factors are involved in various aspects of plant
      development, including maintenance of the biosynthesis and signaling pathways of
      different hormones. However, few direct targets of homeobox proteins have been
      identified. We here show that overexpression of rice homeobox gene HOX1a resulted
      in enhanced gibberellin (GA) response, indicating a positive effect of HOX1a in
      GA signaling. HOX1a is induced by GA and encodes a homeobox transcription factor
      with transcription repression activity. In addition, HOX1a suppresses the
      transcription of early flowering1 (EL1), a negative regulator of GA signaling,
      and further electrophoretic mobility shift assay and chromatin
      immunoprecipitation analysis revealed that HOX1a directly bound to the promoter
      region of EL1 to suppress its expression and stimulate GA signaling. These
      results demonstrate that HOX1a functions as a positive regulator of GA signaling
      by suppressing EL1, providing informative hints on the study of GA signaling.

PMID- 21951843
TI  - PLCepsilon cooperates with the NF-kappaB pathway to augment TNFalpha-stimulated
      CCL2/MCP1 expression in human keratinocyte.
AB  - Phospholipase Cepsilon (PLCepsilon) is a unique class of PLC regulated by both
      Ras family small GTPases and heterotrimeric G proteins. We previously showed by
      using mice bearing its null or transgenic allele that PLCepsilon plays a crucial
      role in various forms of skin inflammation through upregulation of
      proinflammatory cytokine production from keratinocytes. However, molecular
      mechanisms how PLCepsilon augments cytokine production were largely unknown. We
      show here using cultured human keratinocyte PHK16-0b cells that induction of the
      expression of chemokine (C-C motif) ligand 2 (CCL2) following stimulation with
      tumor necrosis factor (TNF)alpha, which primarily depends on the activation of
      the NF-kappaB pathway, is abrogated by small interfering RNA-mediated knockdown
      of PLCepsilon. Enforced expression of PLCepsilon causes substantial CCL2
      expression and cooperates with low level TNFalpha stimulation to induce marked
      overexpression of CCL2, both of which are only partially blocked by
      pharmacological inhibition of the NF-kappaB signaling. However, PLCepsilon
      knockdown exhibits no effect on both the NF-kappaB-cis-element-mediated
      transcription per se and the post-translational modifications of NF-kappaB
      implicated in transcriptional regulation, suggesting that PLCepsilon constitutes
      a yet unknown signaling pathway distinct from the NF-kappaB pathway. This pathway
      can cooperate with the NF-kappaB pathway to achieve a synergistic TNFalpha
      stimulated CCL2 induction in keratinocytes.

PMID- 21951844
TI  - Overexpression of microRNA-29b induces apoptosis of multiple myeloma cells
      through down regulating Mcl-1.
AB  - MicroRNAs (miRNAs) are small, noncoding ribonucleic acids (ncRNAs), which
      regulate gene expression by targeting mRNAs for translational repression and
      degradation. Several lines of evidences have indicated that miRNAs act as tumor
      suppressors and oncogenes. However, the role of miRNAs in pathogenesis of
      multiple myeloma (MM) remains unclear. In this study, we examined the profile of
      miRNA expression of primary MM cells, using miRNA microarray and quantitative
      real-time polymerase chain reaction (qPCR) techniques. These results showed that
      in the bone marrow specimens analyzed, miRNA-29b was significantly downregulated.
      Similar results were also observed in human myeloma cell lines (HMCLs).
      Adenovirus-mediated overexpression of miR-29b induced apoptosis and elevated
      caspase-3 activation in HMCLs. Using a bioinformatics approach, we found a
      perfect complementarity between miRNA-29b and the 3'UTR of myeloid-cell-leukemia
      1(Mcl-1). It is further confirmed that miRNA-29b downregulated the level of Mcl-1
      without effect on the mRNA level using both qRT-PCR assays and Western blot
      analyses. Moreover, we observed that enforced miR-29b expression by using a
      retarget miRNA-29b expression vector (Ad5F11p-miR-29b) could induce apoptosis and
      elevate caspase-3 activation in HMCLs. Our results also indicated that miRNA-29b
      induced apoptosis acted antagonistically with IL-6 in HMCLs. These findings
      suggest that miRNA-29b may play an important role in MM as a tumor suppressor.

PMID- 21951845
TI  - A novel tripolymer coating demonstrating the synergistic effect of chitosan,
      collagen type 1 and hyaluronic acid on osteogenic differentiation of human bone
      marrow derived mesenchymal stem cells.
AB  - The biomimetic approach mimicking in vivo micro environment is the key for
      developing functional tissue engineered constructs. In this study, we used a
      tripolymer combination consisting of a natural polymer, chitosan and two
      extracellular matrix components; collagen type 1 and hyaluronic acid to coat
      tissue culture plate to evaluate their effect on osteogenic differentiation of
      human bone marrow derived mesenchymal stem cells (hMSCs). The polymers were
      blended at different mixing ratios and the tissue culture plates were coated
      either by polyblend method or by surface modification method. hMSCs isolated from
      adult bone marrow were directed to osteoblast differentiation on the coated
      plates. Our results showed that the tripolymer coating of the tissue culture
      plate enhanced mineralization as evidenced by calcium quantification exhibiting
      significantly higher amount of calcium compared to the untreated or individual
      polymer coated plates. We found that the tripolymer coated plates having a 1:1
      mixing ratio of chitosan and collagen type 1, surface modified with hyaluronic
      acid is an ideal combination to achieve the synergistic effect of these polymers
      on in vitro osteogenic differentiation of hMSCs. These results thus, establish a
      novel biomimetic approach of surface modification to enhance osteoblast
      differentiation and mineralization. Our findings hold great promise in
      implementing a biomimetic surface coating to improve osteoconductivity of
      implants and scaffolds for various orthopaedic and bone tissue engineering
      applications.

PMID- 21951846
TI  - Nitrative DNA damage and Oct3/4 expression in urinary bladder cancer with
      Schistosoma haematobium infection.
AB  - To investigate whether mutant stem cells participate in inflammation-related
      carcinogenesis, we performed immunohistochemical analysis to examine nitrative
      and oxidative DNA lesions (8-nitroguanine and 8-oxodG) and a stem cell marker
      Oct3/4 in bladder tissues obtained from cystitis and bladder cancer patients
      infected with Schistosomahaematobium (S. haematobium). We also detected the
      expression of nuclear factor-kappaB (NF-kappaB) and inducible nitric oxide
      synthase (iNOS), which lead to 8-nitroguanine formation. The staining intensity
      of 8-nitroguanine and 8-oxodG was significantly higher in bladder cancer and
      cystitis tissues than in normal tissues. iNOS expression was colocalized with NF
      kappaB in 8-nitroguanine-positive tumor cells from bladder cancer patients.
      Oct3/4 expression was significantly increased in cells from S. haematobium
      associated bladder cancer tissues in comparison to normal bladder and cancer
      tissues without infection. Oct3/4 was also expressed in epithelial cells of
      cystitis patients. Moreover, 8-nitroguanine was formed in Oct3/4-positive stem
      cells in S. haematobium-associated cystitis and cancer tissues. In conclusion,
      inflammation by S.haematobium infection may increase the number of mutant stem
      cells, in which iNOS-dependent DNA damage occurs via NF-kappaB activation,
      leading to tumor development.

PMID- 21951847
TI  - Cysteine 397 plays important roles in the folding of the neuron-restricted
      silencer factor/RE1-silencing transcription factor.
AB  - The neuron-restrictive silencer factor/RE1-silencing transcription factor
      (NRSF/REST) is regarded as not only a key transcriptional repressor but also an
      activator in neuron gene expression by specifically interacting with neuron
      restrictive silencer element (NRSE/RE1) dsDNA and small NRSE/RE1 dsRNA,
      respectively. But its exact mechanism remains unclear. One major problem is that
      it is hard to obtain its functional multiple zinc finger (ZnF) domains in a large
      quantity for further structural studies. To address this issue, in this study, we
      for the first time attained soluble NRSF/REST functional domains named as ZnF5-8,
      ZnF4-8, ZnF3-8 and ZnF2-8 containing four, five, six and seven ZnF motifs in
      tandem, respectively, by using Circular Dichroism (CD) spectrum and two
      dimensional (2D) nucleic magnetic resonance (NMR) (1)H-(1)H NOESY spectrum to
      monitor the folding of each single ZnF peptide. The data indicated that the
      residue cysteine 397 (Cys397) plays important roles in the global folding of
      NRSF/REST multiple ZnFs domain.

PMID- 21951848
TI  - MicroRNA-binding is required for recruitment of human Argonaute 2 to stress
      granules and P-bodies.
AB  - Argonaute proteins are the core components of the RNA-induced silencing complex,
      the central effector of the mammalian RNA interference pathway. In the cytoplasm,
      they associate with at least two types of cytoplasmic RNA granules; processing
      bodies and stress granules, which function in mRNA degradation and translational
      repression, respectively. The significance of Argonaute association with these
      RNA granules is not entirely clear but it is likely related to their activities
      within the RNAi pathway. Understanding what regulates targeting of Argonautes to
      RNA granules may provide clues as to their functions at these organelles. To this
      end, there are a number of conflicting reports that describe the role of small
      RNAs in targeting Argonaute proteins in mammalian cells. We employed quantitative
      microscopic analyses of human Argonaute 2 (hAgo2) mutants to study factors that
      govern localization of this RNA-binding protein to cytoplasmic RNA granules. We
      report, for the first time, that hAgo2 is recruited to stress granules as a
      consequence of its interaction with miRNAs. Moreover, loading of small RNAs onto
      hAgo2 is not required for its stability, suggesting that a pool of unloaded hAgo2
      may exist for extended periods of time in the cytoplasm.

PMID- 21951849
TI  - Low-intensity electromagnetic irradiation of 70.6 and 73 GHz frequencies enhances
      the effects of disulfide bonds reducer on Escherichia coli growth and affects the
      bacterial surface oxidation-reduction state.
AB  - Low-intensity electromagnetic irradiation (EMI) of 70.6 and 73 GHz frequencies
      (flux capacity - 0.06 mW cm(-2)) had bactericidal effects on Escherichia coli.
      This EMI (1h) exposure suppressed the growth of E. coli K-12(lambda). The pH
      value (6.0-8.0) did not significantly affect the growth. The lag-phase duration
      was prolonged, and the growth specific rate was inhibited, and these effects were
      more noticeable after 73 GHz irradiation. These effects were enhanced by the
      addition of DL-dithiothreitol (DTT), a strong reducer of disulfide bonds in
      surface membrane proteins, which in its turn also has bactericidal effect.
      Further, the number of accessible SH-groups in membrane vesicles was markedly
      decreased by EMI that was augmented by N,N'-dicyclohexycarbodiimide and DTT.
      These results indicate a change in the oxidation-reduction state of bacterial
      cell membrane proteins that could be the primary membranous mechanism in the
      bactericidal effects of low-intensity EMI of the 70.6 and 73 GHz frequencies.

PMID- 21951850
TI  - Concanavalin A: a potential anti-neoplastic agent targeting apoptosis, autophagy
      and anti-angiogenesis for cancer therapeutics.
AB  - Concanavalin A (ConA), a Ca(2+)/Mn(2+)-dependent and mannose/glucose-binding
      legume lectin, has drawn a rising attention for its remarkable anti-proliferative
      and anti-tumor activities to a variety of cancer cells. ConA induces programmed
      cell death via mitochondria-mediated, P73-Foxo1a-Bim apoptosis and BNIP3-mediated
      mitochondrial autophagy. Through IKK-NF-kappaB-COX-2, SHP-2-MEK-1-ERK, and SHP-2
      Ras-ERK anti-angiogenic pathways, ConA would inhibit cancer cell survival. In
      addition, ConA stimulates cell immunity and generates an immune memory, resisting
      to the same genotypic tumor. These biological findings shed light on new
      perspectives of ConA as a potential anti-neoplastic agent targeting apoptosis,
      autophagy and anti-angiogenesis in pre-clinical or clinical trials for cancer
      therapeutics.

PMID- 21951851
TI  - Mitochondrial ROS generation for regulation of autophagic pathways in cancer.
AB  - Mitochondria, the main source of reactive oxygen species (ROS), are required for
      cell survival; yet also orchestrate programmed cell death (PCD), referring to
      apoptosis and autophagy. Autophagy is an evolutionarily conserved lysosomal
      degradation process implicated in a wide range of pathological processes, most
      notably cancer. Accumulating evidence has recently revealed that mitochondria may
      generate massive ROS that play the essential role for autophagy regulation, and
      thus sealing the fate of cancer cell. In this review, we summarize mitochondrial
      function and ROS generation, and also highlight ROS-modulated core autophagic
      pathways involved in ATG4-ATG8/LC3, Beclin-1, p53, PTEN, PI3K-Akt-mTOR and MAPK
      signaling in cancer. Therefore, a better understanding of the intricate
      relationships between mitochondrial ROS and autophagy may ultimately allow cancer
      biologists to harness mitochondrial ROS-mediated autophagic pathways for cancer
      drug discovery.

PMID- 21951852
TI  - Interaction abolishment between mutant caveolin-1(Delta62-100) and ABCA1 reduces
      HDL-mediated cellular cholesterol efflux.
AB  - Our previous study shows that caveolin-1 colocalizes and interacts with ATP
      binding cassette transporter A1 (ABCA1), which is intimately involved in cellular
      cholesterol efflux. In this study, we further clarified the region of caveolin-1
      that interacts with ABCA1. We also examined the interaction between mutant
      caveolin-1 and ABCA1 in HDL-mediated cholesterol efflux. We constructed a panel
      of mutant caveolin-1 proteins and co-transfected them into rat aortic endothelial
      and human embryonic kidney 293 (HEK293) cells. The co-immunoprecipitation shows
      that mutant oligomerization domain of caveolin-1, caveolin-1(Delta62-100), is
      required for the interaction of caveolin-1 with ABCA1. Caveolin-1(Delta62-100)
      did not colocalize with ABCA1 in the cholesterol-loaded cells after HDL
      incubation as observed by immunofluorescence confocal microscopy. Concomitantly,
      caveolin-1(Delta62-100) suppressed HDL-mediated cholesterol efflux. The results
      suggest that the region of caveolin-1 between amino acids 62 and 100 is an
      oligomerization domain as well as an attachment site for ABCA1 interaction that
      regulates HDL-mediated cholesterol efflux.

PMID- 21951853
TI  - Senescence marker protein 30 (SMP30)/regucalcin (RGN) expression decreases with
      aging, acute liver injuries and tumors in zebrafish.
AB  - Senescence marker protein 30 (SMP30)/regucalcin (RGN) is known to be related to
      aging, hepatocyte proliferation and tumorigenesis. However, expression and
      function of non-mammalian SMP30/RGN is poorly understood. We found that zebrafish
      SMP30/RGN mRNA expression decreases with aging, partial hepatectomy and
      thioacetamide-induced acute liver injury. SMP30/RGN expression was also greatly
      decreased in a zebrafish liver cell line. In addition, we induced liver tumors in
      adult zebrafish by administering diethylnitrosamine. Decreased expression was
      observed in foci, hepatocellular carcinomas, cholangiocellular carcinomas and
      mixed tumors as compared to the surrounding area. We thus showed the importance
      of SMP30/RGN in liver proliferation and tumorigenesis.

PMID- 21951854
TI  - The involvement of DNA and histone methylation in the repression of IL-1beta
      induced MCP-1 production by hypoxia.
AB  - Hypoxia is a microenvironmental pathophysiologic factor commonly associated with
      tumors and tissue inflammation. We previously reported that hypoxia repressed IL
      1beta-induced monocyte chemoattractant protein-1 (MCP-1) expression. The purpose
      of this study was to investigate the mechanisms involved in the repression of MCP
      1 expression under hypoxia. Treatment of HeLa cells with 5-aza-dC, an inhibitor
      of DNA methylation, abolished the repression of IL-1beta-induced MCP-1 expression
      by hypoxia. A detailed study of the methylation of CpGs sites using bisulfite
      sequencing PCR and 5-methylcytosine immunoprecipitation showed that hypoxia
      induced DNA methylation in both the enhancer and promoter regions of MCP-1in IL
      1beta-treated cells. Next, we analyzed histone methylation within the MCP-1
      promoter and enhancer regions. The level of H3K9 di-methylation, a mark of gene
      repression, in both promoter and enhancer regions was increased by hypoxia in IL
      1beta-treated cells. Our findings suggest that changes in the methylation status
      of CpGs, as well as histone 3 methylation, may represent a critical event in
      transcriptional repression of IL-1beta-induced MCP-1 expression by hypoxia.
      Therefore, DNA methylation is associated with not only epigenetic gene silencing,
      but also with transient transcriptional repression.

PMID- 21951855
TI  - Vesicularization of the endoplasmic reticulum is a fast response to plasma
      membrane injury.
AB  - The endoplasmic reticulum of most cell types mainly consists of an extensive
      network of narrow sheets and tubules. It is well known that an excessive increase
      of the cytosolic Ca(2+) concentration induces a slow but extensive swelling of
      the endoplasmic reticulum into a vesicular morphology. We observed that a similar
      extensive transition to a vesicular morphology may also occur independently of a
      change of cytosolic Ca(2+) and that the change may occur at a time scale of
      seconds. Exposure of various types of cultured cells to saponin selectively
      permeabilized the plasma membrane and resulted in a rapid swelling of the
      endoplasmic reticulum even before a loss of permeability barrier was detectable
      with a low-molecular mass dye. The structural alteration was reversible provided
      the exposure to saponin was not too long. Mechanical damage of the plasma
      membrane resulted in a large-scale transition of the endoplasmic reticulum from a
      tubular to a vesicular morphology within seconds, also in Ca(2+)-depleted cells.
      The rapid onset of the phenomenon suggests that it could perform a physiological
      function. Various mechanisms are discussed whereby endoplasmic reticulum
      vesicularization could assist in protection against cytosolic Ca(2+) overload in
      cellular stress situations like plasma membrane injury.

PMID- 21951856
TI  - Cdk1 and BRCA1 target gamma-tubulin to microtubule domains.
AB  - DNA damage is a critical event that requires an appropriate cellular response.
      This is mediated by checkpoint proteins such as Cdk1 that controls S/G2 and G2/M
      transition. Cdk1 is required for BRCA1 transport to DNA damage sites inside the
      nucleus where BRCA1 functions as a scaffold to initiate a signaling cascade.
      BRCA1 is a multifunctional protein that also ubiquitinates gamma-tubulin and,
      consequently, inhibits microtubule nucleation at the centrosome. Here, we report
      that gamma-tubulin also localizes at confined areas in the microtubule network.
      Nocodazole-mediated microtubule depolymeration results in disappearance of this
      gamma-tubulin fraction, while microtubule stabilization by taxol preserves this
      structure. Surprisingly, overexpression of Cdk1 or BRCA1 greatly expands the
      gamma-tubulin coating of microtubules, suggesting that the microtubule-bound
      gamma-tubulin is involved in DNA damage response. This is in accordance with
      numerous reports of microtubule-associated DNA damage proteins, such as p53, that
      are transported to the nucleus when DNA damage occurs. gamma-Tubulin itself has
      been reported to form complexes with DNA repair proteins in the nucleus.

PMID- 21951857
TI  - Screening for von Willebrand disease: contribution of an automated assay for von
      Willebrand factor activity.
AB  - Measuring von Willebrand factor (VWF) activity is essential to the diagnosis of
      von Willebrand disease (VWD). The VWF activity is usually assessed based on
      measurement of the ristocetin cofactor (VWF:RCo). However, that test is
      technically challenging and has high intra- and inter-assay variabilities. The
      HemosIL VWF activity (VWF:AC) is a fully automated assay, recently proposed as a
      good alternative to VWF:RCo for VWD diagnosis. This study was undertaken to
      assess this new method. First, the analytical performance of VWF:AC on an
      automated coagulo-meter (ACLTop) was determined, and then this new method was
      compared with VWF:RCo and the platelet function analyzer (PFA100) for 160
      patients referred for VWD screening. The VWF:AC achieved acceptable precision
      with within-run and between-run coefficients of variation ranging from 2.3% to
      14.1%, and linearity from 10% to 100%. Despite some marked differences between
      VWF:AC and VWF:RCo for 10 plasmas tested, their agreement for VWD diagnosis was
      good. The VWF:AC had sensitivity similar to that of PFA100 (close to 100%), but
      better specificity (97.7% vs. 66% or 60%, depending on the cartridge used). The
      good analytical performance, and the sensitivity and specificity of VWF:AC to
      detect VWF deficiency renders it a suitable method for VWD screening. Our
      findings support VWF:AC use for the diagnostic work-up of VWD, paying close
      attention to concomitant clinical signs and bleeding score, as recommended for
      VWD.

PMID- 21951858
TI  - Advancing age and bleeding risk are the strongest barriers to anticoagulant
      prescription in atrial fibrillation.

PMID- 21951859
TI  - Anti-biofilm activity of an exopolysaccharide from a sponge-associated strain of
      Bacillus licheniformis.
AB  - BACKGROUND: Secondary metabolites ranging from furanone to exo-polysaccharides
      have been suggested to have anti-biofilm activity in various recent studies.
      Among these, Escherichia coli group II capsular polysaccharides were shown to
      inhibit biofilm formation of a wide range of organisms and more recently marine
      Vibrio sp. were found to secrete complex exopolysaccharides having the potential
      for broad-spectrum biofilm inhibition and disruption. RESULTS: In this study we
      report that a newly identified ca. 1800 kDa polysaccharide having simple
      monomeric units of alpha-D-galactopyranosyl-(1->2)-glycerol-phosphate exerts an
      anti-biofilm activity against a number of both pathogenic and non-pathogenic
      strains without bactericidal effects. This polysaccharide was extracted from a
      Bacillus licheniformis strain associated with the marine organism Spongia
      officinalis. The mechanism of action of this compound is most likely independent
      from quorum sensing, as its structure is unrelated to any of the so far known
      quorum sensing molecules. In our experiments we also found that treatment of
      abiotic surfaces with our polysaccharide reduced the initial adhesion and biofilm
      development of strains such as Escherichia coli PHL628 and Pseudomonas
      fluorescens. CONCLUSION: The polysaccharide isolated from sponge-associated B.
      licheniformis has several features that provide a tool for better exploration of
      novel anti-biofilm compounds. Inhibiting biofilm formation of a wide range of
      bacteria without affecting their growth appears to represent a special feature of
      the polysaccharide described in this report. Further research on such surface
      active compounds might help developing new classes of anti-biofilm molecules with
      broad spectrum activity and more in general will allow exploring of new functions
      for bacterial polysaccharides in the environment.

PMID- 21951861
TI  - Coronary artery calcification score and carotid intima-media  thickness in
      patients with hemophilia.
AB  - BACKGROUND/OBJECTIVES: The traditional view that patients with hemophilia are
      protected against cardiovascular disease is under debate. The aim of the present
      study was to evaluate the presence and extent of atherosclerosis by coronary
      artery calcification score (CACS) and carotid intima media thickness (IMT) in
      patients with hemophilia, and to evaluate their cardiovascular risk profile.
      METHODS: Sixty-nine patients (51 with hemophilia A; 18 with hemophilia B) were
      studied [median age: 52 years (interquartile range [IQR] 43-64)]. Cardiovascular
      risk factors and prior major adverse cardiovascular events (MACEs) were recorded.
      CACS was derived from electron-beam or dual-source computed tomography, and
      carotid IMT was assessed by ultrasound measurements and compared with age
      specific reference values. RESULTS: The median CACS in all patients was 35 (IQR 0
      110) and the geometric mean IMT was 0.80 mm (95% confidence interval [CI] 0.76
      0.84); neither was different from the reference values. Patients with a previous
      MACE (n = 9) had significantly higher CACS and IMT than patients without a
      previous MACE:CACS median 1013 (IQR 530-1306) vs. 0 (IQR 0-67), and IMT geometric
      mean 1.09 mm (95% CI 0.95-1.26) vs. 0.76 mm (95% CI 0.73-0.79), both P < 0.001. A
      higher calculated 10-year cardiovascular risk was related to higher IMT and CACS.
      CONCLUSION: Patients with hemophilia are not protected against the development of
      atherosclerosis as measured by CACS and IMT. The extent of atherosclerosis is
      related to the traditional cardiovascular risk factors. This suggests that
      traditional cardiovascular risk factors should be monitored and treated in
      patients with hemophilia.

PMID- 21951860
TI  - Pseudomonas aeruginosa Psl polysaccharide reduces neutrophil phagocytosis and the
      oxidative response by limiting complement-mediated opsonization.
AB  - Pseudomonas aeruginosa causes chronic lung infections in the airways of cystic
      fibrosis (CF) patients. Psl is an extracellular polysaccharide expressed by non
      mucoid P. aeruginosa strains, which are believed to be initial colonizers. We
      hypothesized that Psl protects P. aeruginosa from host defences within the CF
      lung prior to their conversion to the mucoid phenotype. We discovered that serum
      opsonization significantly increased the production of reactive oxygen species
      (ROS) by neutrophils exposed to a psl-deficient mutant, compared with wild-type
      (WT) and Psl overexpressing strains (Psl(++)). Psl-deficient P. aeruginosa were
      internalized and killed by neutrophils and macrophages more efficiently than WT
      and Psl(++) variants. Deposition of complement components C3, C5 and C7 was
      significantly higher on psl-deficient strains compared with WT and Psl(++)
      bacteria. In an in vivo pulmonary competition assay, there was a 4.5-fold fitness
      advantage for WT over psl-deficient P. aeruginosa. Together, these data show that
      Psl inhibits efficient opsonization, resulting in reduced neutrophil ROS
      production, and decreased killing by phagocytes. This provides a survival
      advantage in vivo. Since phagocytes are critical in early recognition and control
      of infection, therapies aimed at Psl could improve the quality of life for
      patients colonized with P. aeruginosa.

PMID- 21951862
TI  - Parallel manifestations of neuropathologies in the enteric and central nervous
      systems.
AB  - BACKGROUND: Neurodegenerative diseases may extend outside the central nervous
      system (CNS) and involve the gastrointestinal (GI) tract. The gut would appear to
      be a pathological marker for neurodegeneration, as well as a site for studying
      the pathophysiology of neurodegeneration. In fact, both in the ENS and CNS,
      misfolded proteins are likely to initiate a process of neurodegeneration. For
      example, the very same protein aggregates can be detected both in the ENS and
      CNS. In both systems, misfolded proteins are likely to share common cell-to-cell
      diffusion mechanisms, which may occur through a parallel prion-like diffusion
      process. Independently from the enteric or central origin, misfolded proteins may
      proceed along the following steps, they: (i) form aggregates; (ii) are expressed
      on plasma membrane; (iii) are secreted extracellularly; (iv) are glycated to form
      advanced glycation end-products (AGEs); (v) are internalized through specific
      receptors placed on neighboring cells (RAGEs); (vi) are cleared by autophagy; and
      (vii) are neurotoxic. These features are common for a-synuclein (in Parkinson's
      disease and other synucleinopathies), beta-amyloid and tau (in degenerative
      dementia), SOD-1 and TDP43 (in amyotrophic lateral sclerosis), and PrPsc (in
      prion diseases). While in some diseases these features are common to both ENS and
      CNS, in others this remains a working hypothesis. PURPOSE: This review analyzes
      GI alterations from a pathological perspective to assess whether the enteric
      nervous system (ENS) mirrors the neuropathology described in the CNS. We discuss
      the potential mechanisms that lead to the onset and spread of neurodegeneration
      within the gut, from the gut to the brain, and vice versa.

PMID- 21951863
TI  - Cloning and expression analysis of interferon-gamma-inducible-lysosomal thiol
      reductase gene in South African clawed frog (Xenopus laevis).
AB  - In this study, an interferon-gamma-inducible-lysosomal thiol reductase (GILT)
      homologue has been cloned and identified from South African clawed frog Xenopus
      laevis (designated XlGILT). The open reading frame (ORF) of XlGILT consists of
      771 bases encoding a protein of 256 amino acids with an estimated molecular mass
      of 28.76kDa and a theoretical isoelectric point of 5.12. The N-terminus of the
      XlGILT was found to have a putative signal peptide with a cleavage site amino
      acid position at 15-16. SMART analysis showed that the XlGILT contained a GILT
      active-site C(69)GGC(72) motif and a GILT signature motif
      C(114)QHGKEECIGNLIETC(129). The expression levels of XlGILT mRNA were higher in
      spleen and peripheral blood mononuclear cells (PBMCs), moderate in liver,
      intestine, heart and kidney, and lower in lung. The XlGILT mRNA expression was
      significantly up-regulated in spleen in vivo and PBMCs in vitro after LPS
      stimulation. The soluble X. laevis GILT (XlsGILT) was inserted into a pET28a
      vector and expressed in BL21 (DE3) cells as a His-tag fusion enzyme. After
      purification, further study revealed that XlsGILT was capable of catalyzing the
      reduction of the interchain disulfide bonds intact IgG. These results will allow
      for further investigation to unravel the role of this key enzyme in class II MHC
      restricted antigen processing and to use X. laevis as an in vivo model for
      related studies.

PMID- 21951864
TI  - Comparison of particle-exposure triggered pulmonary and systemic inflammation in
      mice fed with three different diets.
AB  - BACKGROUND: Obesity can be linked to disease risks such as diabetes and
      cardiovascular disorders, but recently, the adipose tissue (AT) macrophage also
      emerges as actively participating in inflammation and immune function, producing
      pro- and anti-inflammatory factors. Connections between the AT and chronic lung
      diseases, like emphysema and asthma and a protective role of adipocyte-derived
      proteins against acute lung injury were suggested.In this study we addressed the
      question, whether a diet challenge increases the inflammatory response in the
      alveolar and the blood compartment in response to carbon nanoparticles (CNP), as
      a surrogate for ambient/urban particulate air pollutants. METHODS: Mice were fed
      a high caloric carbohydrate-rich (CA) or a fat-rich (HF) diet for six weeks and
      were compared to mice kept on a purified low fat (LF) diet, respectively.
      Bronchoalveolar lavage (BAL) and blood samples were taken 24 h after
      intratracheal CNP instillation and checked for cellular and molecular markers of
      inflammation. RESULTS AND DISCUSSION: The high caloric diets resulted in distinct
      effects when compared with LF mice, respectively: CA resulted in increased body
      and fat mass without affecting blood cellular immunity. Conversely, HF activated
      the blood system, increasing lymphocyte and neutrophil counts, and resulted in
      slightly increased body fat content. In contrast to higher pro-inflammatory BAL
      Leptin in CA and HF mice, on a cellular level, both diets did not lead to an
      increased pro-inflammatory basal status in the alveolar compartment per se, nor
      did result in differences in the particle-triggered response. However both diets
      resulted in a disturbance of the alveolar capillary barrier as indicated by
      enhanced BAL protein and lactate-dehydrogenase concentrations. Systemically,
      reduced serum Adiponectin in HF mice might be related to the observed white blood
      cell increase. CONCLUSION: The increase in BAL pro-inflammatory factors in high
      caloric groups and reductions in serum concentrations of anti-inflammatory
      factors in HF mice, clearly show diet-specific effects, pointing towards
      augmented systemic inflammatory conditions. Our data suggest that extended
      feeding periods, leading to manifest obesity, are necessary to generate an
      increased susceptibility to particle-induced lung inflammation; although the diet
      challenge already was efficient in driving pro-inflammatory systemic events.

PMID- 21951865
TI  - Bilateral exudative retinal detachment due to retinal pigment epithelial tears
      successfully treated by vitrectomy and scleral window surgery.

PMID- 21951866
TI  - Report on a case of Rothmund-Thomson syndrome associated with esophageal
      stenosis.
AB  - Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive genodermatosis.
      While its incidence is unknown, approximately 300 cases have been reported in the
      literature. The syndrome typically presents with a characteristic facial rash
      (poikiloderma), its diagnostic hallmark, and heterogeneous clinical features
      including congenital skeletal abnormalities, sparse hair distribution, juvenile
      cataracts, and a predisposition to osteosarcoma. Gastrointestinal symptoms, such
      as pyloric stenosis, anal atresia, annular pancreas, and rectovaginal fistula,
      have also been reported sporadically. This is a report describing a patient
      diagnosed with RTS referred to us because of dysphagia caused by esophageal
      stenosis. Long-term results of endoscopic dilation are also presented.

PMID- 21951867
TI  - First report in Italy of the exotic mosquito species Aedes (Finlaya) koreicus, a
      potential vector of arboviruses and filariae.
AB  - BACKGROUND: In the Veneto region (north-eastern Italy) an entomological
      surveillance system has been implemented since the introduction of the Asian
      tiger mosquito (Aedes albopictus) in 1991. During the routine monitoring activity
      in a tiger mosquito-free area, an unexpected mosquito was noticed, which clearly
      did not belong to the recorded Italian fauna. FINDINGS: At the end of May 2011,
      twelve larvae and pupae were collected in a small village in Belluno province
      (Veneto region) from a single manhole. Ten adults reared in the laboratory were
      morphologically and genetically identified as Aedes (Finlaya) koreicus (Edwards,
      1917), a species native to Southeast Asia. The subsequent investigations carried
      out in the following months in the same village provided evidence that this
      species had become established locally. Entomological and epidemiological
      investigations are currently ongoing in the surrounding area, to verify the
      eventual extension of the species outside the village and to trace back the route
      of entry into Italy. CONCLUSIONS: This is the first report in Italy of the
      introduction of the exotic mosquito Ae. koreicus. This species has been shown
      experimentally to be competent in the transmission of the Japanese encephalitis
      virus and of the dog heartworm Dirofilaria immitis and is considered a potential
      vector of other arboviruses. Thus, the establishment of this species may increase
      the current risk or pose new potential threats, for human and animal health. This
      finding considerably complicates the entomological monitoring of the Asian tiger
      mosquito Ae. albopictus in Italy and stresses the importance of implementing the
      entomological surveillance for the early detection of and the rapid response
      against invasive mosquito species.

PMID- 21951869
TI  - Clinicopathological features of non-alcoholic fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic
      liver disease worldwide and its incidence is increasing concomitantly with the
      increase in the prevalence of metabolic syndrome. Fatty liver encompasses a broad
      pathological spectrum of disease, from relatively benign accumulation of fat
      (simple steatosis) to progressive non-alcoholic steatohepatitis (NASH), which is
      associated with necroinflammation and fibrosis. Approximately 20-30% of the
      Japanese population is estimated to have NAFLD, 10% of which is suggested to have
      NASH. The most worrisome feature of NASH is the potential progression to
      cirrhosis, hepatocellular carcinoma (HCC), and finally, mortality. Several
      factors, such as insulin resistance, adipokines, endotoxins and oxidative stress,
      are involved in the pathogenesis of NASH. However, the precise etiological
      mechanism of NAFLD/NASH has yet to be elucidated. This article reviews the
      clinical background, pathogenesis, new diagnostic approaches and future
      directions regarding NAFLD/NASH.

PMID- 21951868
TI  - Novel mutations of TCOF1 gene in European patients with Treacher Collins
      syndrome.
AB  - BACKGROUND: Treacher Collins syndrome (TCS) is one of the most severe autosomal
      dominant congenital disorders of craniofacial development and shows variable
      phenotypic expression. TCS is extremely rare, occurring with an incidence of 1 in
      50.000 live births. The TCS distinguishing characteristics are represented by
      down slanting palpebral fissures, coloboma of the eyelid, micrognathia, microtia
      and other deformity of the ears, hypoplastic zygomatic arches, and macrostomia.
      Conductive hearing loss and cleft palate are often present. TCS results from
      mutations in the TCOF1 gene located on chromosome 5, which encodes a
      serine/alanine-rich nucleolar phospho-protein called Treacle. However,
      alterations in the TCOF1 gene have been implicated in only 81-93% of TCS cases.
      METHODS: In this study, the entire coding regions of the TCOF1 gene, including
      newly described exons 6A and 16A, were sequenced in 46 unrelated subjects
      suspected of TCS clinical indication. RESULTS: Fifteen mutations were reported,
      including twelve novel and three already described in 14 sporadic patients and in
      3 familial cases. Moreover, seven novel polymorphisms were also described. Most
      of the mutations characterised were microdeletions spanning one or more
      nucleotides, in addition to an insertion of one nucleotide in exon 18 and a stop
      mutation. The deletions and the insertion described cause a premature termination
      of translation, resulting in a truncated protein. CONCLUSION: This study confirms
      that almost all the TCOF1 pathogenic mutations fall in the coding region and lead
      to an aberrant protein.

PMID- 21951870
TI  - Liver stiffness measurement using transient elastography and hepatocellular
      carcinoma.
AB  - Liver fibrosis has been gaining noticeable attention because it may lead to end
      stage liver cirrhosis and ultimately to hepatocellular carcinoma. Thus, a precise
      estimation of the degree of liver fibrosis is crucial for predicting prognosis
      and deciding management of patients with chronic liver diseases. Many non
      invasive approaches for the evaluation of liver fibrosis have been developed.
      Among these procedures, transient elastography has recently drawn great
      attention. Transient elastography has been reported to be well correlated with
      the degree of liver fibrosis by many investigators and various institutions.
      Since the degree of liver fibrosis is considered as a strong predictor of risk
      for hepatocellular carcinoma development, several trials have been performed to
      verify the usefulness of measurement of liver stiffness to predict the emergence
      of hepatocellular carcinoma. From these studies, transient elastography seems to
      be a promising procedure to predict the risk of hepatocellular carcinoma;
      however, further cohorts with long-term monitoring of liver stiffness are needed
      to confirm the usefulness of this method.

PMID- 21951871
TI  - Can exercise be a new approach for chronic hepatitis C?

PMID- 21951872
TI  - Dexamethasone attenuates lipopolysaccharide-induced liver injury by
      downregulating glucocorticoid-induced tumor necrosis factor receptor ligand in
      Kupffer cells.
AB  - AIM:   Glucocorticoid-induced tumor necrosis factor receptor ligand (GITRL) plays
      pro-inflammatory roles in immune response. Thus, our aim was to assess if
      dexamethasone attenuates lipopolysaccharide (LPS)-induced liver injury by
      affecting GITRL in Kupffer cells (KC). METHODS:   A BALB/c mouse model of liver
      injury was established by i.p. injecting with LPS (10 mg/kg) co-treated with or
      without dexamethasone (3 mg/kg). Blood and liver samples were obtained for
      analysis of liver morphology, GITRL expression, hepatocellular function and
      cytokine levels at 24 h after injection. KC were isolated and challenged by LPS
      (1 ug/mL), with or without dexamethasone (10 uM) co-treatment, or with GITRL
      siRNA pre-transfection. The GITRL expression and cytokine levels were assayed at
      24 h after challenge. RESULTS:   Dexamethasone treatment significantly improved
      the survival rate of endotoxemic mice (P < 0.05), whereas serum alanine
      aminotransferase, aspartate aminotransferase, tumor necrosis factor (TNF)-alpha,
      interleukin (IL)-6 and gamma-interferon levels were significantly decreased (P <
      0.05, respectively). Concurrently, LPS-induced hepatic tissue injury was
      attenuated as indicated by morphological analysis; and expression of GITRL in
      liver tissue and KC was downregulated (P < 0.05). Consistent with these in vivo
      experiments, inhibited expression of GITRL, TNF-alpha and IL-6 caused by
      dexamethasone treatment were also observed in LPS-stimulated KC. The GITRL, TNF
      alpha and IL-6 expression was also significantly inhibited by GITRL gene
      silencing. CONCLUSION:   The TNF-alpha and IL-6 expression of LPS-stimulated KC
      was inhibited by GITRL gene silencing. Dexamethasone attenuates LPS-induced liver
      injury, at least proportionately, by downregulating GITRL in KC.

PMID- 21951873
TI  - Activation of beta-adrenergic receptors increases the in vitro migration of
      malignant hepatocytes.
AB  - AIM:   Activation of adrenergic receptors (AR) has been reported to enhance the
      growth and invasion of various malignancies. The effects of AR agonists on
      malignant hepatocyte proliferation and migration have yet to be determined.
      METHODS:   PLC/PRF/5 (PLC) and Huh-7 cells were exposed to a wide range of
      concentrations of the AR agonists noradrenaline (NA) and isoprenaline. Cell
      proliferation, migration, intracellular cyclic adenosine monophosphate (cAMP),
      protein kinase A (PKA) and C (PKC), matrix metalloproteinases (MMP)-2, -3, -7 and
      -9, and alpha(1) -, beta(1) - and beta(2) -AR expression were documented in both
      cell lines. RESULTS:   Cell proliferative activity was unaltered following
      exposure to physiological and stress-related concentrations of AR agonists but
      migration was accelerated, an effect that was inhibited by the nonselective beta
      AR antagonist labetalol. cAMP, PKA, PKC or MMP expression remained unchanged.
      Although alpha(1) - and beta(1) -AR expressions were abundant, beta(2) -AR
      expression was limited in both cell lines. CONCLUSION:   Unlike other
      malignancies studied to date, in this study, the proliferative activity of
      malignant hepatocytes was not increased by exposure to AR agonists, a finding
      that could be explained by downregulation of beta(2) -AR expression. The increase
      in malignant hepatocyte migration observed remains unexplained but does not
      appear to involve adenyl cyclase or MMP signaling pathways.

PMID- 21951875
TI  - Acute autoimmune hepatitis.

PMID- 21951874
TI  - Homozygous carrier of the NOD2 1007fs frame-shift mutation presenting with
      refractory community-acquired spontaneous bacterial peritonitis and developing
      fatal pulmonary mucormycosis: A case report.
AB  - Genetic variants of the innate immune system contribute to episodes of
      spontaneous bacterial peritonitis (SBP) in patients with cirrhosis. We herein
      report the case of a patient with the homozygous nucleotide-binding
      oligomerization domain containing 2 (NOD2) frame-shift mutation 1007fs presenting
      with sepsis and community-acquired SBP by Escherichia coli. Secondary
      peritonitis, pancreatic ascites and malignant causes were excluded by extensive
      diagnostic work-up. First-line treatment with ceftriaxone was not successful
      despite in vitro sensitivity of the isolated strain. Despite prolonged second
      line treatment with imipenem/cilastatin and intermittent ascites drainage, the
      ascitic fluid neutrophil count remained markedly elevated in this patient. In the
      course of the disease the patient developed pneumonia with identification of the
      typical hyphae of mucormycosis in the bronchoalveolar lavage and died of sepsis
      with multi-organ failure. On the basis of this observation, variants of the
      innate immunity have to be considered in therapy-refractory SBP, even when they
      are community-acquired and caused by cephalosporin-sensitive Enterobacteriaceae.

PMID- 21951876
TI  - Burden and prevention of viral hepatitis in Bulgaria.
AB  - A meeting of the Viral Hepatitis Prevention Board in Sofia, Bulgaria on 24-25
      March 2011 reviewed the burden and prevention of viral hepatitis in the country.
      It examined the organization and funding of the health system, the surveillance
      systems for infectious diseases, and the epidemiology of viral hepatitis,
      especially the impact of the universal neonatal hepatitis B immunization
      programme introduced almost 20 years ago. It also looked at the implementation of
      new prevention strategies, such as the health mediator concept, as well as
      control measures and monitoring systems. Participants discussed the successes,
      the way forward and possible obstacles.

PMID- 21951878
TI  - Targeting the tick protective antigen subolesin reduces vector infestations and
      pathogen infection by Anaplasma marginale and Babesia bigemina.
AB  - The ultimate goal of vector vaccines is the control of vector infestations while
      reducing pathogen infection and transmission to protect against the many diseases
      caused by vector-borne pathogens. Previously (Vaccine 2011;29:2248-2254), we
      demonstrated that subolesin vaccination and release of tick larvae after
      subolesin knockdown by RNA interference (RNAi) were effective for the control of
      cattle tick, Rhipicephalus (Boophilus) microplus infestations in cattle. In this
      study, we used the fact that these animals were naturally infected with Anaplasma
      marginale and Babesia bigemina to evaluate the effect of subolesin vaccination
      and gene knockdown on tick infection by these cattle tick-transmitted pathogens.
      Ticks fed on vaccinated cattle had lower subolesin mRNA levels when compared to
      controls, resembling RNAi results. A. marginale and B. bigemina infection was
      determined by PCR and decreased by 98% and 99%, respectively in ticks fed on
      vaccinated cattle and by 97% and 99%, respectively after subolesin knockdown.
      These results demonstrated that targeting subolesin expression by vaccination or
      RNAi results in lower subolesin mRNA and pathogen infection levels, probably due
      to the effect of subolesin downregulation on tick feeding, gene expression and
      gut and salivary glands tissue development and function. These results suggested
      that subolesin vaccines could be used for the dual control of tick infestations
      and pathogen infection, a result that could be relevant for other vectors and
      vector-borne pathogens.

PMID- 21951879
TI  - Patient safety: a new paradigm for a health system?

PMID- 21951877
TI  - Bone marrow vaccination: a novel approach to enhance antigen specific antitumor
      immunity.
AB  - Bone marrow (BM) serves as a reservoir for a unique population of memory T cells
      with strong effector properties that make them ideal targets for cancer
      immunotherapy strategies. However, direct vaccination and priming of T cells
      within the BM of the host has never been investigated. This study evaluates the
      specific immune response induced via a new method of direct intra-bone marrow
      (IBM) vaccination in an animal model of human papillomavirus-associated cancer.
      We found that IBM vaccinations with the class I HPV-16 E7 epitope induce large
      numbers of activated, IFN-gamma-producing E7-specific lymphocytes in the BM. In
      prophylactic tumor challenge experiments, direct intra-BM vaccination was found
      to be protective against tumor formation for 80% of the mice. In the therapeutic
      setting, IBM vaccination induced tumor regression in 3 of 10 vaccinated mice and
      delayed tumor growth in the remaining animals. Finally, adoptive transfer of BM
      cells from IBM vaccinated mice to naive animals conferred complete protection
      against tumor growth. These data demonstrate the capacity of direct IBM
      vaccination to induce potent antigen-specific immunity resulting in protection
      from tumor growth in an animal model. Specifically targeting BM T cells with
      vaccines may improve responses to cancer immunotherapy and offer important
      clinical advantages, especially in the setting of bone marrow malignancies.

PMID- 21951880
TI  - Prognostic factors related to mortality in newborns with Bochdalek hernia: a case
      control study.
AB  - BACKGROUND: Bochdalek hernia remains an entity carrying a high mortality. Because
      there are no published studies about prognostic factors for mortality in
      Bochdalek hernia in underdeveloped countries, we designed the present study. Our
      objective was to determine the prognostic factors related to mortality in
      Bochdalek hernia in countries such as Mexico. METHODS: We designed a case
      (deceased)-control (alive) study during a 10-year period analyzing
      epidemiological and pre-, intra- and postoperative factors related to mortality.
      Our protocol is to operate when the patient is hemodynamically stable. RESULTS:
      We analyzed 11 cases and 38 controls. There was pulmonary hypertension in 65% of
      the patients. Associated anomalies were not related to mortality. Low Apgar score
      (p = 0.016), the need for high frequency ventilation (p = 0.003) or having
      postoperative complications (p = 0.025) were related to mortality with pulmonary
      hypertension being the main cause. Odds ratios showed that immediate intubation,
      preoperative pulmonary hypertension (p = 0.05) and the necessity for preoperative
      stabilization (p = 0.043) increased mortality risk by 1.5 times. Using
      preoperative high-frequency ventilation increased the risk nine times and, when
      needed postoperatively, increases the risk 11 times. CONCLUSIONS: Factors related
      to mortality were low Apgar score, immediate intubation, need for stabilization,
      postoperative complications and need for high-frequency ventilation.

PMID- 21951881
TI  - Does the probability of developing ocular trauma-related visual deficiency differ
      between genders?
AB  - BACKGROUND: Ocular trauma affects males more often than females, but the impact
      of this condition regarding visual prognosis is unknown. We undertook this study
      to compare the probability of developing ocular trauma-related visual deficiency
      between genders, as estimated by the ocular trauma score (OTS). METHODS: We
      designed an observational, retrospective, comparative, cross-sectional and open
      label study. Female patients aged >=6 years with ocular trauma were included and
      matched by age and ocular wall status with male patients at a 1:2 male/female
      ratio. Initial trauma features and the probability of developing visual
      deficiency (best corrected visual acuity <20/40) 6 months after the injury, as
      estimated by the OTS, were compared between genders. The proportion and 95%
      confidence intervals (95% CI) of visual deficiency 6 months after the injury were
      estimated. Ocular trauma features and the probability of developing visual
      deficiency were compared between genders (chi(2) and Fisher's exact test); p
      value <0.05 was considered significant. RESULTS: Included were 399 eyes (133 from
      females and 266 from males). Mean age of patients was 25.7 +/- 14.6 years.
      Statistical differences existed in the proportion of zone III in closed globe
      trauma (p = 0.01) and types A (p = 0.04) and type B (p = 0.02) in open globe
      trauma. The distribution of the OTS categories was similar for both genders
      (category 5: p = 0.9); the probability of developing visual deficiency was 32.6%
      (95% CI = 24.6 to 40.5) in females and 33.2% (95% CI = 27.6 to 38.9) in males (p
      = 0.9). CONCLUSIONS: The probability of developing ocular trauma-related visual
      deficiency was similar for both genders. The same standard is required.

PMID- 21951882
TI  - Breast cancer in males.
AB  - BACKGROUND: Male breast cancer has a very low incidence (<1%). It has
      traditionally been considered to have a poorer prognosis than breast cancer in
      females due to delayed diagnosis as a cause of decreased survival. Our goal is to
      analyze our series and to identify factors influencing survival. METHODS: We
      conducted a retrospective study from 1997-2008 (n = 32). Inclusion criteria were
      male gender and histological confirmation of breast cancer. We analyzed
      epidemiological data (age and personal and family history), tumors (size, grade
      of differentiation, histological type, location, TNM stage, receptors),
      therapeutic regimen (surgical technique, adjuvant therapy) and survival (relapse,
      followup, death). RESULTS: Male breast cancer represents 0.9% of all breast
      cancers treated in our center. The average age of our patients was 66.84 years.
      Only 9.3% demonstrated gynecomastia as a presenting complaint. Histologically,
      90% were infiltrating ductal type; 59.25% were diagnosed in early stages (I-II)
      compared to 40.74% in stages III-IV. Aggressive surgical techniques are still
      performed, compared to conservative techniques (74.19% vs. 19.36%). With a median
      follow-up of 52.82 months, the mortality rate was 16%. Existence of distant
      metastasis has been the only statistically significant factor in survival.
      CONCLUSIONS: The percentage of cases of male breast cancer is very low compared
      to breast cancer in females. Limited studies in the literature make gender
      specific findings difficult. A low percentage of conservative surgical procedures
      are performed, even though this has increased considerably in recent years. The
      existence of distant metastasis was the main determinant of survival.

PMID- 21951883
TI  - Pleural effusion and ascites in severe preeclampsia: frequency and correlation
      with plasma colloid osmotic pressure and renal filtration function.
AB  - BACKGROUND: Capillary leak with pleural effusion and/or ascites in severe
      preeclampsia (SP) may be a reason for low plasma colloid osmotic pressure (PCOP)
      and deterioration of renal filtration function. The objective of this study was
      to report the frequency of pleural effusion and/or ascites in patients with SP
      and to compare the correlation with PCOP and renal filtration function. METHODS:
      We conducted a cross-sectional study that included 92 pregnant women with SP. In
      52 patients, no fluid collections were demonstrated and in 40 patients the
      findings were positive. Correlation with PCOP and endogenous creatinine clearance
      (CrCl) was calculated. Student t test and Pearson correlation coefficient (r)
      were used for statistical analysis. RESULTS: Frequency of fluid collections was
      43.48% (ascites, 16 cases; pleural effusion, 12 cases; and ascites with pleural
      effusion, 12 cases). PCOP in patients without and with collections were different
      (20.12 +/- 2.16 vs. 18.78 +/- 2.58 mm Hg, respectively; p = 0.009) as well as
      with endogenous CrCl (111.69 +/- 37.61 vs. 95.27 +/- 34.22 ml/min/1.73 m(2) SC *
      0.85; p = 0.03). Correlation coefficient (r) of PCOP was negative with all the
      fluid collections (ascites -0.25, pleural effusion -0.29, ascites with pleural
      effusion -0.02 and -0.30) as well as the r of endogenous CrCl (ascites -0.01,
      pleural effusion -0.13, ascites with pleural effusion -0.27 and -0.67).
      CONCLUSIONS: Frequency of collections was very high (43.48%). A weak negative
      correlation with PCOP and endogenous CrCl was found.

PMID- 21951884
TI  - Hydatid liver disease: our 25-year experience.
AB  - BACKGROUND: Hydatid disease is a zoonosis caused by Echinococcus spp., which
      inhabits the intestine of some canines (dog). Humans are accidental intermediate
      hosts and can accommodate one or more cysts in different locations, mainly the
      liver and lungs. The standard treatment of hydatid disease has historically been
      surgical, including conservative and radical procedures. The disease is
      considered endemic in the area around Hospital Provincial "Domingo Funes,"
      Cordoba, Argentina. METHODS: We conducted a retrospective and descriptive study
      that included 57 patients diagnosed with hydatid liver disease who were treated
      surgically from January 1985 to December 2009. RESULTS: Females represented 50.9%
      of the subjects with a mean age of 53 years. The main clinical presentation was
      pain in 56% of patients and palpable mass in 33.3%. In 93% of cases we used
      ultrasonography as a diagnostic method (100% sensitivity). Erythrocyte
      sedimentation rate was increased in 63%. Total cystectomy was performed on 47.4%
      of patients. Surgical morbidity was 29.8%. Surgical mortality was zero. The
      average number of days of hospitalization was 12. CONCLUSIONS: Clinical and
      epidemiological analysis is the mainstay of diagnosis, supplemented by
      ultrasound, CT scan and blood tests. We suggest total cystectomy as the first
      surgical choice, when feasible, due to its lower morbidity/mortality and shorter
      postoperative hospital stay, according to similar series.

PMID- 21951885
TI  - Identification of prognostic factors in pancreatic cancer.
AB  - BACKGROUND: Surgical resection is the only potentially curative treatment for
      pancreatic cancer, but it is associated with high complication rates. Outcome is
      poor, even in those resected cases. Identification of prognostic factors
      preoperatively may help to improve treatment of these patients, based on the
      expected response. METHODS: A retrospective study of clinical variables of 59
      patients with histological diagnosis of pancreatic carcinoma at University
      Hospitals Ramon y Cajal and La Princesa (Madrid, Spain) between 1999 and 2003 was
      performed. RESULTS: We analyzed 59 patients (32 males and 27 females) with a mean
      age of 63.76 years. All patients were operated on, performing palliative surgery
      in 32% and tumor resection in 68%, including pancreaticoduodenectomy in 51% and
      distal pancreatectomy in 17%. Median overall survival was 14 months (range: 1-110
      months). We observed that the presence of abdominal pain (p = 0.042) and back
      pain (p = 0.004) at diagnosis, palpation of abdominal mass at physical
      examination (p = 0.012), preoperative levels of hemoglobin <12 g/dl (p = 0.0006)
      and serum albumin <2.8 g/dl (p = 0.021), perineural infiltration (p = 0.025),
      lymph node affection (p = 0.004), stages II, III, and IV (p = 0.001), and
      presence of residual tumor (R+) (p = 0.008) are all associated with poor
      survival. CONCLUSIONS: Abdominal and back pain, palpation of abdominal mass at
      physical examination, preoperative levels of hemoglobin <12 g/dl and serum
      albumin <2.8 g/dl, perineural infiltration, lymph node affection, stages II, III,
      and IV, and the presence of residual tumor are associated with poor outcome.

PMID- 21951886
TI  - Surgical wound infection in general surgery.
AB  - BACKGROUND: The registration of cases of surgical site infection (SSI) for the
      period of hospitalization has a bias whose magnitude is not known in our
      environment. The aim of this study was to measure the incidence of SSI in primary
      interventions for patients using an ambulatory monitoring system. METHODS: We
      designed a cross-sectional, descriptive study of patients undergoing primary
      surgery. All patients were assessed at the 2nd, 7th and 21st day after surgery.
      We used criteria of wound infection according to the Centers for Disease Control
      and Prevention (CDC), Atlanta, GA. Comparison of variables was performed using
      chi(2) and Fisher's exact test. Analysis of variables related to the risk of SSI
      and the control variables was performed using logistic regression. RESULTS: Of
      152 patients (107 males and 45 females), 32 were diagnosed with SSI at 48 h and
      at 7 and 21 days after surgery, respectively. The type of surgery (emergency),
      surgical risk according to the American Society of Anesthesiologists (ASA),
      duration of surgery, body mass index (BMI) and underlying diseases are predictors
      of SSI and were statistically significant (p <0.05). Culture was performed in 32
      cases and Escherichia coli were isolated in 25%. CONCLUSIONS: In this series of
      unselected patients, the incidence of SSI reached 21.1% after a 1-month minimum
      follow-up.

PMID- 21951887
TI  - Cervical bronchogenic cyst mimicking thyroglossal cyst: case report and
      literature review.
AB  - BACKGROUND: Bronchogenic cysts are rare congenital malformations of ventral
      foregut development, often with an intrathoracic location. Presentation at the
      cervical region is very rare. CLINICAL CASE: We present the case of a 29-year-old
      female who demonstrated a 3-cm medial neck mass in relation to the hyoid
      cartilage. The mass was painless with a rubbery consistency, moving with tongue
      movements. Cervical ultrasonography and thyroid scan were suggestive of
      nonfunctioning thyroglossal cyst. Histopathological examination revealed the
      presence of a cervical bronchogenic cyst. CONCLUSIONS: Cervical bronchogenic cyst
      is a rare congenital malformation that usually appears as a painless neck mass.
      Imaging findings are not specific for differentiating thyroid, thyroglossal,
      branchial or thymus cyst; therefore, clinical observation of an asymptomatic
      lateral neck mass in an adult should include the possibility of a bronchogenic
      cyst in the differential diagnosis.

PMID- 21951888
TI  - Long-term follow-up and pregnancy in a patient with neurenteric cyst: case
      report.
AB  - BACKGROUND: Neurenteric cysts (NC) are rare congenital anomalies. Cysts are
      secretory with an epithelial lining and features that resemble those of
      gastrointestinal and/or respiratory mucosa. They originate embryologically and
      result from an incomplete separation of the neurenteric canal from the foregut.
      CLINICAL CASE: We describe the 21-year follow-up of a female patient with a
      history of partial control of urinary and anal sphincters. The patient had a 6
      month course of pain associated with saddle hypoesthesia, limited gait, chronic
      constipation, plus inferior paresthesia of the limbs. These features, along with
      the MRI findings, were compatible with the diagnosis of neurenteric cyst. The
      patient underwent two surgical procedures. We used a nonradical approach because
      of the connection of the cyst with the rectum and nerves in the deep plane. At
      age 22, she became pregnant and, after an uneventful gestation, gave birth to a
      healthy newborn. DISCUSSION: The selection of surgical strategy is oriented to
      mass effect resolution. In accordance with the literature, evaluation of the best
      choice for each patient is mandatory to obtain a balance of the risk and the
      potential functional preservation. This report demonstrates the importance of
      sensory and motor function preservation instead of using aggressive treatment.
      CONCLUSION: Our goal in each procedure was symptom alleviation, reduction of cyst
      size, clearance of the mass effect, and an attempt to resect the cyst capsule as
      much as possible without compromising quality of life and neurological functions.

PMID- 21951889
TI  - Laparoscopic management of retrocaval ureter: case report and literature review.
AB  - BACKGROUND: Retrocaval ureter is a rare congenital anomaly with an incidence of
      approx. 1/1000 live births. Recently, the laparoscopic approach has become the
      gold standard for treatment, relegating open surgery as a second option. CLINICAL
      CASE: We present the case of a 27-year-old male with a 2-year history of colicky
      pain in the right flank radiating to the ipsilateral thigh and genital region.
      The patient was initially treated with a right double-pigtail catheter stent due
      to obstructive uropathy as evidenced by ultrasound. He underwent laparoscopic
      ureteral anteposition with a successful outcome and has remained asymptomatic
      during a 12-month follow-up. CONCLUSIONS: Retrocaval ureter is a rare entity that
      requires a high grade of suspicion for initial diagnosis to provide adequate and
      opportune treatment that will have repercussions on kidney function and quality
      of life for the patient. Open surgery has traditionally been the treatment of
      choice; however, in recent decades laparoscopic surgery has been practiced more
      during this era of minimally invasive therapy, without yet displacing open
      surgery in our country.

PMID- 21951890
TI  - Interposition of gracilis muscle for rectourethral fistula repair: case report.
AB  - BACKGROUND: Rectourethral fistula is a rare disease with a difficult surgical
      treatment. The etiology of rectourethral fistula is iatrogenic, secondary to
      prostate surgery, pelvic radiotherapy and a rare complication of rectal surgery.
      Surgical treatment options for rectourethral fistula are diverse. Interposition
      of gracilis muscle has a curative index of 100% with close surveillance, as
      reported by Nyham. CLINICAL CASE: We present a case of a 58-year-old male with
      iatrogenic rectourethral fistula secondary to radical prostatectomy and who was
      treated with interposition of the gracilis muscle. Eight weeks after surgery and
      with colostomy closed, no evidence of recurrence was detected. CONCLUSIONS:
      Interposition of the gracilis muscle requires a multidisciplinary approach and
      demonstrates good shortterm results.

PMID- 21951891
TI  - Malignant degeneration in pilonidal disease.
AB  - BACKGROUND: Pilonidal disease is one of the most frequent entities in our daily
      surgical activity. Although it is a benign disease, malignant degeneration is
      likely to occur in pilonidal disease. We reviewed surgical interventions for
      pilonidal diseases performed from January 1, 1995 to December 31, 2008. CLINICAL
      CASE: We reviewed all 3729 histology reports obtained after surgical removal of
      pilonidal disease. There were three cases of squamous cell carcinoma and one case
      of basal cell carcinoma. Patients affected by squamous cell carcinoma had a mean
      age of 54.2 years and a mean time of evolution of the lesions of 20.6 years. We
      found local recurrence and lymph node recurrence. Mean follow-up period was 5
      years and there was no mortality. The patient with basal cell carcinoma had 1
      year of pilonidal disease evolution. There were no recurrences. CONCLUSIONS:
      Malignancy can arise in pilonidal diseases with a long evolution time. There is a
      high rate of recurrence and morbimortality in cases of squamous cell carcinomas.
      Adjuvant radiotherapy in addition to complete local excision has demonstrated a
      decrease in the rate of local recurrence.

PMID- 21951892
TI  - Improvement results in paraesophageal hernia.
AB  - Paraesophageal hernias account for between 5 and 14% of hiatal hernias. Surgical
      management is complex and is currently one of the most debated subjects in
      surgery. Every symptomatic patient with a paraesophageal hernia  and no
      contraindication for surgery should undergo repair. It is important to perform an
      evaluation that includes medical history, chest x-rays, barium swallow, upper
      endoscopy and manometry. Surgical approaches include open thoracic and abdominal
      access. Recently, laparoscopic surgery has become an option with less morbidity
      and mortality with results similar to open surgery. Essential technical aspects
      to improve results are reduction of the hernia sac, recognition and management of
      the short esophagus, hiatal closure and an antireflux procedure. Despite
      improving recurrence rates, use of synthetic mesh for hiatal closure has been
      associated with catastrophic complications; therefore, use of biologic mesh is
      preferred.

PMID- 21951893
TI  - Robotic-assisted laparoscopic surgery of the colon and rectum: a literature
      review.
AB  - Although it has been almost a decade since the implementation of robotic
      colorectal surgery, this modality remains under development. The aim of this
      study is to briefly describe, based on a literature review, the current role of
      robotic surgery of the colon and rectum. This emerging technique has revealed
      some benefits such as an improvement in visualization in 3D, image magnification
      up to 10 times the actual size, and better maneuverability with wrist-like
      movements offered by the da Vinci(r) Surgical System. This system is composed of
      the robotic console in which the surgeon performs the movements to be
      accomplished by the robot. The latter presents up to three articulated arms for
      instrumentation as well as the camera arm. Even though the safety and feasibility
      of robotic colon surgery has been demonstrated, there is no complete
      manifestation of the advantages of this technique due to the wide surgical field
      in the abdominal cavity and freedom of movement achieved with other minimally
      invasive techniques. Robotic rectal surgery represents a different scenario since
      the advantages of the da Vinci(r) system are maximally expressed in the confined
      pelvic cavity. Consequently, in some specialized centers, the robotic modality
      represents the first therapeutic choice for resectable rectal cancer. Robotic
      assisted laparoscopy has demonstrated to be a feasible and safe approach in
      colorectal surgery and presents some advantages over other techniques in regards
      to perioperative outcomes. Nonetheless, costs and availability represent the main
      limitations of this technology.

PMID- 21951894
TI  - Maladaptive schemas as a mediator between social defeat and positive symptoms in
      young people at clinical high risk for psychosis.
AB  - AIM: Social defeat may be the mechanism that links past social adversities with
      the development of psychosis. In depression research, it is accepted that adverse
      early social experiences can lead to enduring cognitive vulnerabilities,
      characterized by negative schemas about the self and others. The aim of this
      study was to examine whether negative beliefs about the self and others link
      social defeat to early signs of psychosis. METHODS: Data from a sample of
      individuals at high risk for developing psychosis (n = 38) were assessed using
      measures of social defeat and schemas. RESULTS: High levels of social defeat and
      negative evaluations of the self and others were displayed. Negative beliefs
      mediated the relationship between social defeat and early symptoms, offering some
      support for the notion that maladaptive self-beliefs play a role in the onset of
      psychosis. CONCLUSIONS: These results have implications for prevention because
      these maladaptive schemas are malleable factors for which we have effective
      psychological interventions.

PMID- 21951896
TI  - Methionine/galactose ratio on newborn blood spots useful for reduction of false
      positives for homocystinuria and galactosemia by high-performance anion-exchange
      chromatography with pulsed amperometric detection.
AB  - BACKGROUND: Methionine (Met) in blood and urine is a useful diagnostic marker for
      homocystinuria (HCU). However, galactosemia could be misdiagnosed as HCU when Met
      is used as the sole marker, since elevated excretion of Met presents in both
      galactosemia and HCU. Use of a more specific diagnostic marker in addition to Met
      is therefore necessary for reduction of false positive results for HCU as well as
      confirmative diagnosis of HCU. METHODS: Chromatographic separation was performed
      using an anion-exchange column. The levels of Met and galactose (Gal) on blood
      were measured and Met/Gal ratios were calculated from blood spot samples from 300
      normal volunteers, eight galactosemia patients, and three HCU patients. RESULTS:
      The Met/Gal ratio ranged 0-4.95 for normal blood spots (n=300), 0-0.22 for
      galactosemia samples (n=8), and >1250 for HCU patient samples. CONCLUSIONS:
      Separation, extraction, and deproteinization procedures were established for Met
      and Gal in blood spots. And Met/Gal ratio allowed HCU to clearly distinguish from
      galactosemia. As a way of second tier confirmative analysis, the ratio is the
      best way to reduce false positives. The assay is most appropriate to reduce false
      positives in labs that do not screen for galactosemia.

PMID- 21951897
TI  - Evaluation of genetic trends and determination of the optimal number of
      cumulative records of parity required in reproductive traits in a Large White pig
      population.
AB  - Genetic improvement of the reproductive performance of pigs is important for pig
      breeding despite their low heritabilities. The objectives of this study were to
      investigate the effectiveness of selection concerning reproductive traits and to
      determine the optimal number of parity records required for accurate estimation
      of breeding values (BVs) in the open population of a commercial pig breeding
      company. The study used records of 2220 purebred Large White pigs (9845 litters)
      farrowed between 1998 and 2009 in the two herds of the Pacific Ocean Breeding Co.
      Ltd. The traits studied included farrowing interval (FI), total number of piglets
      at birth (TNB), average weaning weight per litter (AWW), and raising rate (RR). A
      statistical model was applied to the 4-trait repeatability animal model. The
      heritabilities of FI, TNB, AWW and RR were low. The genetic trends in TNB (h(2) =
      0.09) showed approximately 1.0 increase in 6 years from 2003 to 2008. The
      predicted error variances indicated that up to fourth parity records are
      necessary for accurate genetic evaluation. The present study results indicated
      that even reproductive traits with low heritability can be improved.

PMID- 21951898
TI  - Substitution within erythropoietin receptor gene D1 domain associated with litter
      size in Beijing Black pig, Sus scrofa.
AB  - Studies of uterine capacity and litter size in swine have suggested that
      erythropoietin receptor (EPOR) plays an important role in fetal survival through
      maturation of red blood cells. In this study, we screened the porcine EPOR gene
      for mutations and identified three single nucleotide polymorphisms (SNPs): two
      missense mutations and one synonymous mutation. We then genotyped 272 Beijing
      Black sows, Sus scrofa, and compared this data with litter sizes from a total of
      1523 parities among the sows. The G allele of the nonsynonymous SNP, EPOR
      c.434A>G, was associated with greater litter size at both first parity (P < 0.05)
      and at later parities (P < 0.01). This SNP causes His92Arg adjacent to the fourth
      conserved cysteine residue in the mature protein and is in the D1 domain of the
      protein. Additionally, we determined the allele frequencies for this SNP among
      six Chinese indigenous pig breeds (Bamei, Erhualian, Laiwu Black, Mashen, Meishan
      and Min) and three Western commercial pig breeds (Duroc, Landrace and Large
      White). The c.434G allele was significantly more common among the more prolific
      Chinese breeds than the Western breeds, implying that EPOR c.434A>G could be a
      useful genetic marker to improve litter size in swine.

PMID- 21951899
TI  - Fine mapping the number of corpora lutea quantitative trait loci on SSC3:
      analysis of the porcine follicle-stimulating hormone receptor gene.
AB  - In females, follicle-stimulating hormone (FSH) targets a FSH receptor (FSHR)
      expressed only on granulose cells, inducing maturation of the ovarian follicles.
      We hypothesized that genetic variants in the FSHR gene influence litter size by
      affecting the number of corpora lutea. We fine-mapped a region of Sus Scrofa
      chromosome 3 that contains quantitative trait loci for corpora lutea.
      Polymorphisms were detected in the exons and 5' flanking region of the porcine
      FSHR gene, a positional candidate for the statistically most significant of the
      quantitative trait loci. Finally, 248 F(2) animals from a Duroc and Meishan cross
      were genotyped for three FSHR SNPs at positions 74, 532 and 1166, and these were
      correlated with the phenotypes of litter size and corpus luteum number. Three
      haplotypes were identified: M1 (G/G/C), M2 (C/A/T) and D (C/A/C). In the F(2)
      population, the M1 haplotype was associated with a greater number of corpora
      lutea (P < 0.01) and also seemed to be associated with increased litter size,
      although the association was not significant (P = 0.2571). Some polymorphisms
      resulting in amino acid substitutions in these genes were excluded from the
      polymorphisms possibly responsible for the number of corpora lutea.

PMID- 21951900
TI  - Identification of lactic acid bacteria isolated from corn stovers.
AB  - One hundred and twenty-six strains were isolated from corn stover in Henan
      Province, China, of which 105 isolates were considered to be lactic acid bacteria
      (LAB) according to Gram-positive, catalase-negative and mainly metabolic lactic
      acid product. Analysis of the 16S ribosomal DNA sequence of 21 representative
      strains was used to confirm the presence of the predominant groups and to
      determine the phylogenetic affiliation of isolates. The sequences from the
      various LAB isolates showed high degrees of similarity to those of the GenBank
      type strains between 99.4% and 100%. The prevalent LAB, predominantly
      Lactobacillus (85.6%), consisted of L. plantarum (33.3%), L. pentosus (28.6%) and
      L. brevis (23.7%). Other LAB species as Leuconostoc lactis (4.8%), Weissella
      cibaria (4.8%) and Enterococcus mundtii (4.8%) also presented in corn stover. The
      present study is the first to fully document corn stover-associated LAB involved
      in the silage fermentation. The identification results revealed LAB composition
      inhabiting corn stover and enabling the future design of appropriate inoculants
      aimed at improving the fermentation quality of silage.

PMID- 21951901
TI  - Effect of field pea (Pisum sativum L.) level on intake, digestion, ruminal
      fermentation and in vitro gas production in sheep fed maintenance diets.
AB  - The objective of this study was the characterization of the nutritive value,
      ruminal fermentation and nutrient digestibility of field pea (Pisum sativum L.)
      hay (FPH) by-product through in situ, in vitro and in vivo tests. A FPH diet was
      administered ad libitum to four sheep (live weight (LW) 38.0 +/- 2.0 kg) at four
      inclusion levels (0, 25, 50 and 75%) over a conventional sorghum grain/oat straw
      ration in a 4 * 4 Latin square design. The in situ degradability of FPH was 67%
      dry matter (DM), 71% crude protein and 66% neutral detergent fiber (NDF). The
      inclusion of FPH did not affect (P >= 0.05) the DM (61 +/- 0.4 g/LW(0.75) /day)
      and organic matter (OM) intake (56 +/- 0.7 g/LW(0.75) /day). Total DM
      digestibility (68 +/- 2.5%), OM (70 +/- 3%), and NDF (60 +/- 3%), were not
      different (P >= 0.05) between control and FPH inclusion diets. The diet had no
      effect on ruminal pH, ruminal ammonia concentration, total and individual
      volatile fatty acids. The chemical composition and sheep intake behavior indicate
      that FPH by-product is medium quality forage when incorporated in maintenance
      rations.

PMID- 21951902
TI  - Analysis of methanogenic archaeal communities of rumen fluid and rumen particles
      from Korean black goats.
AB  - Molecular diversity of methanogens in the rumen of Korean black goats was
      investigated with 16S rRNA gene clone libraries using methanogen-specific
      primers. The libraries were composed of rumen fluid-associated methanogens (FAM)
      and rumen particle-associated methanogens (PAM) from rumen-fistulated Korean
      black goats. Among the 141 clones of the FAM library, the sequences were mostly
      related to two phyla, the Methanobacteriaceae family (77.3%) and the
      Thermoplasmatales family (22.7%); and among the 68 clones of the PAM library,
      sequences were also mainly clustered in the two phyla, the Thermoplasmatales
      family (63.24%) and the Methanobacteriaceae family (35.29%). Most of the
      sequenced clones in the two libraries were closely related to uncultured
      methanogenic archaeon. Quantitative real-time PCR revealed that PAM (8.97 log 10)
      had significantly higher (P < 0.01) density of methanogens by the methanogenic
      16S rRNA gene copies than FAM (7.57 log 10). The two clone libraries also showed
      difference in Shannon index (FAM library 1.70 and PAM library 1.59) and Chao 1
      estimator (FAM library 18 and PAM library 17 operational taxonomic units).
      Apparent differences found in the microbial community from the two 16S rRNA gene
      libraries could be a result of such factors as the chemical and physical nature
      of the target material surface, types or component of diets, the interaction
      between the methanogens and other microbes, and age of the experimental goats.

PMID- 21951903
TI  - Measurement of carbonic anhydrase isozyme VI (CA-VI) in swine sera, colostrums,
      saliva, bile, seminal plasma and tissues.
AB  - Swine secretory carbonic anhydrase VI (CA-VI) was purified from swine saliva and
      an antibody to CA-VI was generated. A specific and sensitive enzyme-linked
      immunosorbent assay (ELISA) has been developed for the measurement of swine CA
      VI. The assay can detect as little as 5 ng/mL of swine CA-VI. Typical standard
      curves were determined for a range of CA-VI solutions (7.8 to 500 ng/mL). The
      coefficients of variation for these solutions were less than 5%. When 500, 250 or
      100 ng/mL of swine CA-VI was added to swine sera, the recoveries were 102.0%,
      109.7% and 100.2%, respectively. The concentrations of CA-VI in the saliva (26.2
      +/- 30.4 ug/mL), sera (3.3 +/- 4.9 ng/mL), bile (153.0 +/- 114.0 ng/mL), seminal
      plasma (124.0 +/- 39.0 ng/mL) and parotid gland (441.3 +/- 90.0 ug/g wet tissue),
      submaxillary gland (88.1 +/- 124.4 ug/g wet tissue), sublingual gland (58.6 +/-
      24.6 ug/g wet tissue) and gallbladder (2.4 +/- 1.3 ug/1g wet tissue) were
      determined by ELISA. The concentration of CA-VI in colostrum was 163.3 +/- 101.4
      ng/mL and did not decrease within 10 days following parturition. An
      immunohistochemical reaction to anti-CA-VI antiserum was observed in the columnar
      epithelial cells lining the gallbladder. These data suggest that secretory CA-VI
      plays various roles in pH regulation and the maintenance of ion and fluid
      balance.

PMID- 21951904
TI  - Calcitonin receptor binding in the hen anterior pituitary during an oviposition
      cycle.
AB  - The equilibrium dissociation constant (K(d) ) and the maximum binding capacity
      (B(max) ) of calcitonin (CT) receptor in the plasma membrane of the anterior
      pituitary in hens were examined by Scatchard analysis of specific binding of
      (125) I-labeled chicken CT. Values of K(d) and B(max) of CT receptor were smaller
      in laying hens than in non-laying hens. A decrease in the K(d) and B(max) value
      of CT receptor was observed in the anterior pituitary after the injection of
      estradiol-17beta and progesterone into nonlaying hens, but not changed after the
      injection of 5alpha-dihydrotestosterone. During an oviposition cycle, the K(d)
      and the B(max) value decreased 3 h before oviposition. In non-laying hens,
      neither the K(d) nor the B(max) value changed during a full day period. The
      present study suggests that the CT action on the anterior pituitary may increase
      3 h before oviposition by the effect of estradiol-17beta and progesterone in
      laying hens.

PMID- 21951905
TI  - Early milk availability modulates the activity of choline acetyltransferase in
      the cerebral cortex of rats.
AB  - The purpose of the present study was to investigate the effect of milk in the
      early stage of lactation on the maturation of cholinergic neurons in the cerebral
      cortex of rats. Pups were removed from their mothers immediately following
      parturition and placed with foster dams at days 5-7 of lactation. At days 18 and
      56 after birth, the activity of choline acetyltransferase (ChAT), an enzyme
      responsible for acetylcholine synthesis, in different areas of the cerebral
      cortex was examined by high-performance liquid chromatography electrochemical
      detection. In the frontal and hindlimb/parietal regions of the cerebral cortex,
      the lack of early milk significantly decreased ChAT activity at days 18 and 56.
      There was no effect on gains in the body or brain weight of infants. ChAT
      activity in the occipital area tended to be lower in the early milk-deprived
      rats. The intake of early milk potentially contributes not only to nutrients for
      the growth of newborn infants, but also to the functional maturation of the
      cholinergic neurotransmission system in a region-specific manner.

PMID- 21951906
TI  - Relationship between adipose maturity and fatty acid composition in various
      adipose tissues of Japanese Black, Holstein and Crossbred (F1) steers.
AB  - The amount of monounsaturated fatty acid (MUFA) is intimately related to adipose
      softness, melting point (MP) and flavor in beef. Stearoyl-CoA desaturase (SCD) is
      a main gene involved in MUFA synthesis. Mature adipose tends to be highly
      saturated, whereas immature or maturing adipose is highly unsaturated when
      chronologically based, so the degree of non-saturation can be an index of adipose
      maturity. In this study, three different adipose tissues (coelomic (CL),
      perirenal (PR), and subcutaneous (SC)) from three beef breeds with differing
      slaughter ages (Japanese Black (29.5 months), Holstein (20.1 month), and F1
      crossbreed (25.6 months)) were examined to: (i) determine adipose maturity level
      as indexed by MUFA %; and (ii) determine SCD and other lipogenic gene messenger
      RNA (mRNA) expression levels in relation to unsaturated fatty acid content. Fatty
      acid composition was significantly different between adipose tissues (P < 0.05).
      MUFA amount was high in the following order: SC > CL > PR. This pattern
      corresponded to SCD mRNA expression profile showing higher expression in SC than
      CL and PR. However, Japanese black cattle are an exception with CL adipose
      containing similar UFA % as SC adipose, yet having the lowest SCD mRNA expression
      level among all adipose tissues tested. Therefore, SCD mRNA expression and MUFA %
      appear to be directly related; however, differences in SCD mRNA expression among
      three adipose tissues may reflect differences in the fat development
      characteristics affected by chronological age of the cattle breeds.

PMID- 21951907
TI  - Changes in the bovine whey proteome during the early lactation period.
AB  - To investigate time-dependent change in the bovine whey proteome during the early
      lactation period, a two-dimensional gel-based approach was used in this study.
      Milk samples were collected from five healthy Friesian-Holstein dairy cows up to
      10 days postpartum. Spot patterns of whey proteins varied drastically from
      immediately after parturition to 48 h, but no significant changes occurred
      thereafter. Protein identification by mass spectrometry revealed that the ratios
      of caseins and immunoglobulins drastically decreased during 48 h postpartum,
      while those of lower molecular mass proteins such as alpha-lactalbumin and beta
      lactoglobulin increased. More than 100 spots were detected, being much more
      abundant in colostral whey than in mature milk whey. Of a total of 25 proteins
      identified, four, viz. zinc-alpha-2-glycoprotein, vitamin D-binding protein,
      immunoglobulin G2 chain C and beta2-microglobulin, were detectable only in
      colostrum. Our results indicate that most of the minor whey proteins in colostrum
      relate to the passive immunity of newborn calves, but some of them play
      significant roles in nutritional supplementation of the neonate. The
      characteristics of whey proteins in transition imply that enhancement of innate
      immunity becomes more important than protection of the neonate against pathogens
      via passive immunity after 48 h postpartum.

PMID- 21951908
TI  - Effect of temperature on survival of pathogenic bacteria in biogas plants.
AB  - The paper deals with the hygienic advantages of sanitation to treat dairy manure
      in full-scale biogas plants. The slurry samples were collected from two
      thermophilic biogas plants (55 degrees C) and two mesophilic biogas plants (38
      degrees C) in Hokkaido Japan. A detectable number of Coli-aerogenes group and
      Enterococcus in the slurries after anaerobic digestion (AD) could not be found in
      either thermophilic biogas plants. However, in both mesophilic biogas plants the
      viable numbers of Coli-aerogenes group and Enterococcus were detected in the
      slurries even after anaerobic digestion. The mean decimation reduction time
      (T(90) ) values of the Coli-aerogenes group and Enterococcus in the slurries
      during mesophilic digestion were 13.3 days and 16.7 days, respectively.

PMID- 21951909
TI  - Partial sequence of Mongolian gerbil (Meriones unguiculatus) immunoglobulin gamma
      heavy chain constant region.
AB  - We determined the sequence of the immunoglobulin gamma heavy-chain constant
      (IGHC) region of the Mongolian gerbil (Meriones unguiculatus). To isolate a part
      of the IGHC complementary DNA, we designed primers on the basis of highly
      conserved sequences in mouse, rat and hamster. The deduced IGHC is structurally
      similar to counterparts in other mammalian species and shows 84.6% identity to
      the IGHC of hamster IgG, 76.6% to rat IgG1, 83.3% to rat IgG2a, 78.1% to mouse
      IgG1, 81.8% to mouse IgG2a, 79.1% to mouse IgG2b and 79.2% to mouse IgG3 at the
      nucleotide level. The results suggest that gerbil IgG is closely related to
      hamster IgG and rat IgG2a.

PMID- 21951910
TI  - Cheating, trade-offs and the evolution of aggressiveness in a natural pathogen
      population.
AB  - The evolutionary dynamics of pathogens are critically important for disease
      outcomes, prevalence and emergence. In this study we investigate ecological
      conditions that may promote the long-term maintenance of virulence polymorphisms
      in pathogen populations. Recent theory predicts that evolution towards increased
      virulence can be reversed if less-aggressive social 'cheats' exploit more
      aggressive 'cooperator' pathogens. However, there is no evidence that social
      exploitation operates within natural pathogen populations. We show that for the
      bacterium Pseudomonas syringae, major polymorphisms for pathogenicity are
      maintained at unexpectedly high frequencies in populations infecting the host
      Arabidopsis thaliana. Experiments reveal that less-aggressive strains
      substantially increase their growth potential in mixed infections and have a
      fitness advantage in non-host environments. These results suggest that niche
      differentiation can contribute to the maintenance of virulence polymorphisms, and
      that both within-host and between-host growth rates modulate cheating and
      cooperation in P. syringae populations.

PMID- 21951911
TI  - In vitro activities of novel 4-HPR derivatives on a panel of rhabdoid and other
      tumor cell lines.
AB  - BACKGROUND: Rhabdoid tumors (RTs) are aggressive pediatric malignancies with poor
      prognosis. N-(4-hydroxy phenyl) retinamide (4-HPR or fenretinide) is a potential
      chemotherapeutic for RTs with activity correlated to its ability to down-modulate
      Cyclin D1. Previously, we synthesized novel halogen-substituted and
      peptidomimetic-derivatives of 4-HPR that retained activity in MON RT cells. Here
      we analyzed the effect of 4-HPR in inhibiting the growth of several RT, glioma,
      and breast cancer cell lines and tested their effect on cell cycle, apoptosis and
      Cyclin D1 expression. METHODS: Effect of compounds on RT cell cycle profiles, and
      cell death were assessed by MTS cell survival assays and FACS analysis. The
      effects of treatment on Cyclin D1 expression were determined by immunoblotting.
      The efficacy of these compounds on glioma and breast cancer cell lines was also
      determined using MTS assays. RESULTS: Low micromolar concentrations of 4-HPR
      derivatives inhibited cell survival of all RT cells tested. The 4-HPR derivatives
      altered RT cell cycle profiles and induced high levels of cell death that was
      correlated with their potency. ATRA exhibited high IC50 values in all cell lines
      tested and did not cause cell death. In MON RT cells, the iodo-substituted
      compounds were more active than 4-HPR in inducing cell cycle arrest and
      apoptosis. Additionally, the activity of the compounds correlated with their
      ability to down-modulate Cyclin D1: while active compounds reduced Cyclin D1
      levels, inactive ATRA did not. In glioma and breast cancer cell lines, 4-HPR and
      4-HPR derivatives showed variable efficacy. CONCLUSIONS: Here we demonstrate, for
      the first time, that the inhibitory activities of novel halogen-substituted and
      peptidomimetic derivatives of 4-HPR are correlated to their ability to induce
      cell death and down-modulate Cyclin D1. These 4-HPR derivatives showed varied
      potencies in breast cancer and glioma cell lines. These data indicate that
      further studies are warranted on these derivatives of 4-HPR due to their low
      IC50s in RT cells. These derivatives are of general interest, as conjugation of
      halogen radioisotopes such as 18F, 124I, or 131I to 4-HPR will allow us to
      combine chemotherapy and radiotherapy with a single drug, and to perform
      PET/SPECT imaging studies in the future.

PMID- 21951914
TI  - Phylogeny and evolution of bracts and bracteoles in Tacca (Dioscoreaceae).
AB  - Most species in the genus Tacca (Dioscoreaceae) feature green to black purple,
      conspicuous inflorescence involucral bracts with variable shapes, motile filiform
      appendages (bracteoles), and diverse types of inflorescence morphology. To infer
      the evolution of these inflorescence traits, we reconstructed the molecular
      phylogeny of the genus, using DNA sequences from one nuclear, one mitochondrial,
      and three plastid loci (Internal Transcribed Spacer (ITS), atpA, rbcL, trnL-F,
      and trnH-psbA). Involucres and bracteoles characters were mapped onto the
      phylogeny to analyze the sequence of inflorescence trait evolution. In all
      analyses, species with showy involucres and bracteoles formed the most derived
      clade, while ancestral Tacca had small and plain involucres and short bracteoles,
      namely less conspicuous inflorescence structures. Two of the species with the
      most elaborate inflorescence morphologies (T. chantrieri in southeast China and
      T. integrifolia in Tibet), are predominantly self-pollinated, indicating that
      these conspicuous floral displays have other functions rather than pollinator
      attraction. We hypothesize that the motile bracteoles and involucres may
      facilitate selfing; display photosynthesis in the dim understory, and protect
      flowers from herbivory.

PMID- 21951913
TI  - Transplantation of human neural stem/progenitor cells overexpressing galectin-1
      improves functional recovery from focal brain ischemia in the Mongolian gerbil.
AB  - Transplantation of human neural stem/progenitor cells (hNSPCs) is a promising
      method to regenerate tissue from damage and recover function in various
      neurological diseases including brain ischemia. Galectin-1(Gal1) is a lectin that
      is expressed in damaged brain areas after ischemia. Here, we characterized the
      detailed Gal1 expression pattern in an animal model of brain ischemia. After
      brain ischemia, Gal1 was expressed in reactive astrocytes within and around the
      infarcted region, and its expression diminished over time. Previously, we showed
      that infusion of human Gal1 protein (hGal1) resulted in functional recovery after
      brain ischemia but failed to reduce the volume of the ischemic region. This
      prompted us to examine whether the combination of hNSPCs-transplantation and
      stable delivery of hGal1 around the ischemic region could reduce the ischemic
      volume and promote better functional recovery after brain ischemia. In this
      study, we transplanted hNSPCs that stably overexpressed hGal1 (hGal1-hNSPCs) in a
      model of unilateral focal brain ischemia using Mongolian gerbils. Indeed, we
      found that transplantation of hGal1-hNSPCs both reduced the ischemic volume and
      improved deficits in motor function after brain ischemia to a greater extent than
      the transplantation of hNSPCs alone. This study provides evidence for a potential
      application of hGal1 with hNSPCs-transplantation in the treatment of brain
      ischemia.

PMID- 21951915
TI  - Association of C1QB gene polymorphism with schizophrenia in Armenian population.
AB  - BACKGROUND: Schizophrenia is a complex, multifactorial psychiatric disorder. Our
      previous findings indicated that altered functional activity of the complement
      system, a major mediator of the immune response, is implicated in the
      pathogenesis of schizophrenia. In order to explore whether these alterations are
      genetically determined or not, in the present study we evaluated the possible
      association of complement C1Q component gene variants with susceptibility to
      schizophrenia in Armenian population, focusing on four frequent single nucleotide
      polymorphisms (SNPs) of C1QA and C1QB genes. METHODS: In the present study four
      SNPs of the complement C1Q component genes (C1QA: rs292001, C1QB rs291982,
      rs631090, rs913243) were investigated in schizophrenia-affected and healthy
      subjects. Unrelated Caucasian individuals of Armenian nationality, 225
      schizophrenic patients and the same number of age- and sex-matched healthy
      subjects, were genotyped. Genotyping was performed using polymerase chain
      reaction with sequence-specific primers (PCR-SSP) and quantitative real-time
      (qRT) PCR methods. RESULTS: While there was no association between C1QA rs292001,
      C1QB rs913243 and rs631090 genetic variants and schizophrenia, the C1QB
      rs291982*G minor allele was significantly overrepresented in schizophrenic
      patients (G allele frequency 58%) when compared to healthy subjects (46%, OR =
      1.64, p(corr) = 0.0008). Importantly, the susceptibility for schizophrenia was
      particularly associated with C1QB rs291982 GG genotype (OR = 2.5, p(corrected) =
      9.6E-5). CONCLUSIONS: The results obtained suggest that C1QB gene may be
      considered as a relevant candidate gene for susceptibility to schizophrenia, and
      its rs291982*G minor allele might represent a risk factor for schizophrenia at
      least in Armenian population. Replication in other centers/populations is
      necessary to verify this conclusion.

PMID- 21951916
TI  - Nonmuscle myosin IIA is associated with poor prognosis of esophageal squamous
      cancer.
AB  - Nonmuscle myosin IIA (myosin IIA) is a force-producing protein involved in the
      process of cell migration. Its expression has been considered as a bad prognostic
      indicator in stage I lung adenocarcinoma. However, the expression and clinical
      significance of myosin IIA in esophageal cancer has not been explored. In this
      study, we investigate the expression level of myosin IIA in 50 esophageal
      squamous cancer and 30 adjacent normal esophageal tissues by immunohistochemical
      staining and correlated its expression with clinicopathological features. Myosin
      IIA was expressed in all esophageal squamous cancer tissues (100%) and 8 of 30
      adjacent normal tissues (26.7%, P = 0.000). In cancer tissues, elevated myosin
      IIA expression level was significantly correlated with increasing metastatic
      lymph nodes, poorer cancer differentiation, and advanced tumor stage. Further
      univariate analysis suggested that strong myosin IIA expression was associated
      with a significantly shorter overall survival (P = 0.021). In addition, MYH9
      SiRNA was transfected into esophageal squamous cancer cell line (KYSE-510) to
      study the role of myosin IIA in cell migration. SiRNA-mediated depletion of
      myosin IIA in KYSE-510 cells significantly increased cell-matrix adhesion and
      attenuated cell migration ability (P = 0.000). In conclusion, these findings
      indicate that overexpression of myosin IIA may contribute to the progression and
      poor prognosis of esophageal squamous cancer, and this effect may be associated
      with increased cancer cell migration.

PMID- 21951918
TI  - Stimulation of blood mononuclear cells with bacterial virulence factors leads to
      the release of pro-coagulant and pro-inflammatory microparticles.
AB  - Severe infectious diseases remain a major and life-threatening health problem. In
      serious cases a systemic activation of the coagulation cascade and hypovolemic
      shock are critical complications that are associated with high mortality rates.
      Here we report that blood mononuclear cells, stimulated with M1 protein of
      Streptococcus pyogenes or other bacterial virulence factors, produce not only pro
      coagulant, but also pro-inflammatory microparticles (MPs). Our results also show
      that activation of the contact system on MPs contributes to these two effects.
      Phosphatidylserine (PS) plays an important role in these processes as its
      upregulation on MPs allows an assembly and activation of the contact system. This
      in turn results in stabilization of the tissue factor-induced clot and a
      processing of high-molecular-weight kininogen by plasma kallikrein followed by
      the release of bradykinin, a potent vascular mediator. Pro-coagulant monocyte
      derived MPs were identified in plasma samples from septic patients and further
      analysis of MPs from these patients revealed that their pro-coagulant activity is
      dependent on the tissue factor- and contact system-driven pathway.

PMID- 21951917
TI  - Genetic evidence for an essential role of neuronally expressed IL-6 signal
      transducer gp130 in the induction and maintenance of experimentally induced
      mechanical hypersensitivity in vivo and in vitro.
AB  - Tenderness and mechanical allodynia are key symptoms of malignant tumor,
      inflammation and neuropathy. The proinflammatory cytokine interleukin-6 (IL-6) is
      causally involved in all three pathologies. IL-6 not only regulates innate
      immunity and inflammation but also causes nociceptor sensitization and
      hyperalgesia. In general and in most cell types including immune cells and
      sensory neurons, IL-6 binds soluble MU receptor subunits which heteromerizes with
      membrane bound IL-6 signal transducer gp130. In the present study, we used a
      conditional knock-out strategy to investigate the importance of signal transducer
      gp130 expressed in C nociceptors for the generation and maintenance of mechanical
      hypersensitivity. Nociceptors were sensitized to mechanical stimuli by
      experimental tumor and this nociceptor sensitization was preserved at later
      stages of the pathology in control mice. However, in mice with a conditional
      deletion of gp130 in Nav1.8 expressing nociceptors mechanical hypersensitivity by
      experimental tumor, nerve injury or inflammation recovery was not preserved in
      the maintenance phase and nociceptors exhibited normal mechanical thresholds
      comparable to untreated mice. Together, the results argue for IL-6 signal
      transducer gp130 as an essential prerequisite in nociceptors for long-term
      mechanical hypersensitivity associated with cancer, inflammation and nerve
      injury.

PMID- 21951919
TI  - Carboxylesterase expression in human dental pulp cells: role in regulation of
      BisGMA-induced prostanoid production and cytotoxicity.
AB  - Biocompatibility of dentin bonding agents (DBA) and composite resin may affect
      the treatment outcome (e.g., healthy pulp, pulpal inflammation, pulp necrosis)
      after operative restoration. Bisphenol-glycidyl methacrylate (BisGMA) is one of
      the major monomers present in DBA and resin. Prior studies focused on salivary
      esterase for metabolism and degradation of resin monomers clinically. This study
      found that human dental pulp cells expressed mainly carboxylesterase-2 (CES2) and
      smaller amounts of CES1A1 and CES3 isoforms. Exposure to BisGMA stimulated CES
      isoforms expression of pulp cells, and this event was inhibited by catalase.
      Exogenous addition of porcine esterase prevented BisGMA- and DBA-induced
      cytotoxicity. Interestingly, inhibition of CES by bis(p-nitrophenyl) phosphate
      (BNPP) and CES2 by loperamide enhanced the cytotoxicity of BisGMA and DBA.
      Addition of porcine esterase or N-acetyl-l-cysteine prevented BisGMA-induced
      prostaglandin E(2) (PGE(2)) and PGF(2alpha) production. In contrast, addition of
      BNPP and loperamide, but not mevastatin, enhanced BisGMA-induced PGE(2) and
      PGF(2alpha) production in dental pulp cells. These results suggest that BisGMA
      may induce the cytotoxicity and prostanoid production of pulp cells, leading to
      pulpal inflammation or necrosis via reactive oxygen species production.
      Expression of CES, especially CES2, in dental pulp cells can be an adaptive
      response to protect dental pulp against BisGMA-induced cytotoxicity and
      prostanoid release. Resin monomers are the main toxic components in DBA, and the
      ester group is crucial for monomer toxicity.

PMID- 21951920
TI  - Corrosion fatigue of biomedical metallic alloys: mechanisms and mitigation.
AB  - Cyclic stresses are often related to the premature mechanical failure of metallic
      biomaterials. The complex interaction between fatigue and corrosion in the
      physiological environment has been subject of many investigations. In this
      context, microstructure, heat treatments, plastic deformation, surface finishing
      and coatings have decisive influence on the mechanisms of fatigue crack
      nucleation and growth. Furthermore, wear is frequently present and contributes to
      the process. However, despite all the effort at elucidating the mechanisms that
      govern corrosion fatigue of biomedical alloys, failures continue to occur. This
      work reviews the literature on corrosion-fatigue-related phenomena of Ti alloys,
      surgical stainless steels, Co-Cr-Mo and Mg alloys. The aim was to discuss the
      correlation between structural and surface aspects of these materials and the
      onset of fatigue in the highly saline environment of the human body. By
      understanding such correlation, mitigation of corrosion fatigue failure may be
      achieved in a reliable scientific-based manner. Different mitigation methods are
      also reviewed and discussed throughout the text. It is intended that the
      information condensed in this article should be a valuable tool in the
      development of increasingly successful designs against the corrosion fatigue of
      metallic implants.

PMID- 21951921
TI  - Automated calculation of the distal contractile integral in esophageal pressure
      topography with a region-growing algorithm.
AB  - BACKGROUND: The distal contractile integral (DCI) is an index of contractile
      vigor in high-resolution esophageal pressure topography (EPT) calculated as the
      product of amplitude, duration, and span of the distal esophageal contraction.
      The aim of this study was to develop an automated algorithm calculating DCI.
      METHODS: The DCI was calculated conventionally using ManoViewTM (Given Imaging,
      Los Angeles, CA, USA) software in EPT studies from 72 controls and 20 patients
      and compared to the calculation using a MATLABTM (Version 7.9.0, R2009b; The
      MathWorks Inc., Natick, MA, USA) 'region-growing' algorithm. This algorithm first
      established the spatial limits of the distal contraction (the proximal pressure
      trough to either the distal pressure trough or to the superior margin of the
      lower esophageal sphincter at rest). Pixel-by-pixel horizontal line segments were
      then analyzed within this span starting at the pressure maximum and extending
      outward from that point. The limits of 'region-growing' were defined either by
      the spatial DCI limits or by encountering a pressure <20 mmHg. The DCI was then
      calculated as the total units of mmHg s cm greater than 20 mmHg within this
      domain. KEY RESULTS: Excellent correlation existed between the two methods (r =
      0.98, P < 0.001). The DCI values obtained with the conventional calculation were
      slightly but significantly greater than with the region-growing algorithm.
      Differences were attributed to the inclusion of vascular pressures in the
      conventional calculation or to differences in localization of the distal limit of
      the DCI. CONCLUSIONS & INFERENCES: The proposed region-growing algorithm provides
      an automated method to calculate DCI that limits inclusion of vascular pressure
      artifacts and minimizes the need for user input in data analysis.

PMID- 21951922
TI  - Efficacy of pitavastatin for the treatment of non-alcoholic steatohepatitis with
      dyslipidemia: An open-label, pilot study.
AB  - AIM:   Non-alcoholic fatty liver disease (NAFLD) that encompasses a spectrum of
      liver disorders characterized by simple steatosis, non-alcoholic steatohepatitis
      (NASH) through cirrhosis, is becoming an important chronic liver disease in
      Japan. Currently, there is no proven therapy for NASH. In this study, we assessed
      the efficacy of statin therapy in NASH patients with dyslipidemia. METHODS:  
      Twenty patients with biopsy-proven NASH with dyslipidemia who agreed to
      participate in this multicentric prospective study were enrolled. The patients
      were treated for 12 months with pitavastatin 2 mg/day. Clinical and histological
      alterations were comparatively evaluated before and after treatment. Standard
      weight loss counseling was continued during the treatment period. Follow-up liver
      biopsy was performed in 13 patients. RESULTS:   Twenty-five percent of patients
      had hyperlipoproteinemia type IIa and 75% had hyperlipoproteinemia type IIb at
      baseline. The levels of alanine aminotransferase, gamma-glutamyl transpeptidase
      and lipid profiles were significantly improved by the treatment with pitavastatin
      for 12 months. Especially, these improvements were prominent in NASH patients
      with hyperlipoproteinemia type IIb. While non-alcoholic fatty liver disease
      activity score and fibrosis stage did not change significantly in all patients,
      they did improve in 54% and 42% in individual patients, respectively. CONCLUSION:
      NASH-related metabolic parameters improved with therapy including histology in
      some patients. However, three of 13 patients had progression of fibrosis during
      the treatment. Our pilot study demonstrated the efficacy of pitavastatin for the
      treatment of NASH with dyslipidemia, especially with hyperlipoproteinemia type
      IIb and controlled trials are needed in the future.

PMID- 21951923
TI  - Visual impairment among school children in urban Central India: the Central India
      Children Eye Study.

PMID- 21951924
TI  - Virtue, progress and practice.

PMID- 21951925
TI  - Four alternatives to a reductive view of knowledge: a commentary.

PMID- 21951926
TI  - Tacit clues and the science of clinical judgement [a commentary on Henry et al].

PMID- 21951927
TI  - De-mystifying tacit knowing and clues: a comment on Henry et al.

PMID- 21951928
TI  - Opportunities and risks in gauging practitioners' ethical commitments--commentary
      on Little et al.

PMID- 21951929
TI  - Criticizing the data: some concerns about empirical approaches to ethics.
AB  - There are strong arguments in favour of the need for more 'empirically informed
      philosophy'. Using papers in the current issue of JECP as case studies, I raise
      fundamental and unresolved methodological questions about the proper relationship
      between philosophy and empirical research, in particular concerning the
      relationship between 'data' in empirical research and the 'responses' people give
      in to questions in the process of philosophical dialogue. There are tensions
      between the role of data in empirical research and the critical stance required
      for philosophy that need to be addressed, if empirically informed philosophy is
      to make a serious and substantial contribution to our thinking about the matters
      of great import it addresses.

PMID- 21951930
TI  - The value of evidence and evidence of values: bringing together values-based and
      evidence-based practice in policy and service development in mental health.

PMID- 21951931
TI  - Radical liberal values-based practice.

PMID- 21951932
TI  - Values-based practice and bioethics: close friends rather than distant relatives.
      Commentary on 'Fulford (2011). The value of evidence and evidence of values:
      bringing together values-based and evidence-based practice in policy and service
      development in mental health'.

PMID- 21951933
TI  - Which values? And whose? A reply to Fulford.

PMID- 21951934
TI  - The philosopher's task: value-based practice and bringing to consciousness
      underlying philosophical commitments.

PMID- 21951935
TI  - Epistemology and ethics of evidence-based medicine: a response to comments.

PMID- 21951937
TI  - Abortion and referrals for abortion: is the law in need of change?

PMID- 21951938
TI  - Taking Procrustes' Axe to Professor Fisher's response.

PMID- 21951939
TI  - Interdisciplinary workshop on concepts of health and disease: report.

PMID- 21951941
TI  - Evaluation of secondary school teachers' knowledge about psychosis: a
      contribution to early detection.
AB  - AIMS: We sought to evaluate secondary school teachers' knowledge about psychosis
      and their level of interest in this topic given the key role they may be able to
      play in the early detection of psychosis. METHODS: A questionnaire survey of 268
      secondary school teachers from eight secondary schools within the Azienda
      Sanitaria Locale Rome/E and Rome/A catchment areas (two of the five city health
      districts) in Rome. Teachers were asked to complete the Italian version
      Esperienza e Conoscenza delle Difficolto Sociali ed Emotive dei Giovani of the
      Knowledge and Experience of Social Emotional Difficulties among Young people self
      report questionnaire that investigates the diagnosis, age of onset, aetiology,
      prognosis and treatment of psychosis. They were also asked about their experience
      with pupils with possible psychosis. RESULTS: Most of teachers were able to
      recognize psychotic symptoms from a case vignette. Approximately 25% of the
      teachers had experienced a pupil with possible symptoms of psychosis. However,
      teachers displayed little awareness of psychiatric community services available
      for young people. CONCLUSIONS: Our study shows that teachers may play an
      important role in early detection and psychosis prevention strategies. The
      teachers also displayed a keen interest in gaining a deeper knowledge of early
      psychotic signs and in cooperating closely with a mental health specialist to
      obtain guidance and support when faced with serious mentally ill pupils.

PMID- 21951942
TI  - The clinical effectiveness and cost-effectiveness of different surveillance
      mammography regimens after the treatment for primary breast cancer: systematic
      reviews registry database analyses and economic evaluation.
AB  - BACKGROUND: Following primary breast cancer treatment, the early detection of
      ipsilateral breast tumour recurrence (IBTR) or ipsilateral secondary cancer in
      the treated breast and detection of new primary cancers in the contralateral
      breast is beneficial for survival. Surveillance mammography is used to detect
      these cancers, but the optimal frequency of surveillance and the length of follow
      up are unclear. OBJECTIVES: To identify feasible management strategies for
      surveillance and follow-up of women after treatment for primary breast cancer in
      a UK setting, and to determine the effectiveness and cost-effectiveness of
      differing regimens. METHODS: A survey of UK breast surgeons and radiologists to
      identify current surveillance mammography regimens and inform feasible
      alternatives; two discrete systematic reviews of evidence published from 1990 to
      mid 2009 to determine (i) the clinical effectiveness and cost-effectiveness of
      differing surveillance mammography regimens for patient health outcomes and (ii)
      the test performance of surveillance mammography in the detection of IBTR and
      metachronous contralateral breast cancer (MCBC); statistical analysis of
      individual patient data (West Midlands Cancer Intelligence Unit Breast Cancer
      Registry and Edinburgh data sets); and economic modelling using the systematic
      reviews results, existing data sets, and focused searches for specific data
      analysis to determine the effectiveness and cost-utility of differing
      surveillance regimens. RESULTS: The majority of survey respondents initiate
      surveillance mammography 12 months after breast-conserving surgery (BCS) (87%) or
      mastectomy (79%). Annual surveillance mammography was most commonly reported for
      women after BCS or after mastectomy (72% and 53%, respectively). Most (74%)
      discharge women from surveillance mammography, most frequently 10 years after
      surgery. The majority (82%) discharge from clinical follow-up, most frequently at
      5 years. Combining initiation, frequency and duration of surveillance mammography
      resulted in 54 differing surveillance regimens for women after BCS and 56 for
      women following mastectomy. The eight studies included in the clinical
      effectiveness systematic review suggest surveillance mammography offers a
      survival benefit compared with a surveillance regimen that does not include
      surveillance mammography. Nine studies were included in the test performance
      systematic review. For routine IBTR detection, surveillance mammography
      sensitivity ranged from 64% to 67% and specificity ranged from 85% to 97%. For
      magnetic resonance imaging (MRI), sensitivity ranged from 86% to 100% and
      specificity was 93%. For non-routine IBTR detection, sensitivity and specificity
      for surveillance mammography ranged from 50% to 83% and from 57% to 75%,
      respectively, and for MRI from 93% to 100% and from 88% to 96%, respectively. For
      routine MCBC detection, one study reported sensitivity of 67% and specificity of
      50% for both surveillance mammography and MRI, although this was a highly select
      population. Data set analysis showed that IBTR has an adverse effect on survival.
      Furthermore, women experiencing a second tumour measuring >20 mm in diameter were
      at a significantly greater risk of death than those with no recurrence or those
      whose tumour was <10 mm in diameter. In the base-case analysis, the strategy with
      the highest net benefit, and most likely to be considered cost-effective, was
      surveillance mammography alone, provided every 12 months at a societal
      willingness to pay for a quality-adjusted life-year of either L20,000 or L30,000.
      The incremental cost-effectiveness ratio for surveillance mammography alone every
      12 months compared with no surveillance was L4727. LIMITATIONS: Few studies met
      the review inclusion criteria and none of the studies was a randomised controlled
      trial. The limited and variable nature of the data available precluded any
      quantitative analysis. There was no useable evidence contained in the Breast
      Cancer Registry database to assess the effectiveness of surveillance mammography
      directly. The results of the economic model should be considered exploratory and
      interpreted with caution given the paucity of data available to inform the
      economic model. CONCLUSIONS: Surveillance is likely to improve survival and
      patients should gain maximum benefit through optimal use of resources, with those
      women with a greater likelihood of developing IBTR or MCBC being offered more
      comprehensive and more frequent surveillance. Further evidence is required to
      make a robust and informed judgement on the effectiveness of surveillance
      mammography and follow-up. The utility of national data sets could be improved
      and there is a need for high-quality, direct head-to-head studies comparing the
      diagnostic accuracy of tests used in the surveillance population. FUNDING: The
      National Institute for Health Research Health Technology Assessment programme.

PMID- 21951943
TI  - Differences in clinical manifestations between childhood-onset lupus and adult
      onset lupus: a meta-analysis.
AB  - OBJECTIVE: It is known that age at disease onset has an impact on the clinical
      course and outcome of systemic lupus erythematosus (SLE); however, the precise
      differences in the prevalence of SLE manifestations are debated. Our objective
      was to conduct a systematic literature review and meta-analysis of all studies
      that directly compare childhood-onset lupus with adult-onset lupus to determine
      which clinical manifestations vary with age at disease onset. METHODS: A
      comprehensive literature search of the MEDLINE/PubMed,EMBASE, CINAHL, and SCOPUS
      databases was conducted to identify relevant articles. Study quality was assessed
      using the STROBE checklist. Study sample characteristics and clinical
      manifestation event rates were extracted from each study. Pooled odds ratios
      (ORs) were calculated using the random effects method, and between-study
      heterogeneity was quantified using the I (2) statistic. RESULTS: Of the 484
      studies identified by the search strategy, 16 were included in this review. The
      total number of patients was 5993 adults and 905 children with SLE. Study quality
      was on average 16/32, ranging from 8 to 29. Several statistically significant
      differences were found: malar rash, ulcers/mucocutaneous involvement, renal
      involvement, proteinuria, urinary cellular casts, seizures, thrombocytopenia,
      hemolytic anemia, fever, and lymphadenopathy were more common in childhood-onset
      SLE with ORs ranging from 1.3 to 3.7; however, Raynaud's, pleuritis, and sicca
      were more common in adult-onset SLE (twice as common). CONCLUSIONS: The results
      of this meta-analysis suggest that some clinical manifestations of lupus are
      different in childhood-onset SLE and adult-onset SLE.

PMID- 21951944
TI  - The effects of cyclophosphamide and mycophenolate on end-stage renal disease and
      death of lupus nephritis.
AB  - Debate continues about the optimal treatment modality of lupus nephritis (LN). We
      compared the efficacy and safety of intravenous cyclophosphamide (CYC) and
      mycophenolate mofetil (MMF) for LN treatment in Korea. After searching for
      systemic lupus erythematosus (SLE) patients diagnosed between 1998 and 2007 with
      the diagnostic code of ICD10, we selected the 71 patients who were treated with
      CYC or MMF without any other immunosuppressant except systemic steroid. Composite
      outcome was defined as progression to end-stage renal disease (ESRD) and/or all
      cause mortality. The initial manifestations of the CYC group were more severe
      than those of the MMF group. The mean daily MMF dose was 980  +/-  100  mg for
      21.67  +/-  18.25 months. The mean monthly dose per CYC pulse therapy was 850  +/
      30  mg for 17.04  +/-  13.15 months. The incidence of composite outcome was
      5/20 (25%) in the MMF group and 4/51 (7.8%) in the CYC group. The relative risk
      (RR) for composite outcome in the CYC group was 0.249 (95% CI for RR: 0.067
      0.934, p = 0.039) compared with the MMF group with Cox's hazard proportional
      analysis. In Kaplan-Meier analysis, the probability of composite outcome was
      lower in the CYC group than in the MMF group (Log rank test p-value = 0.026). The
      results of this retrospective study suggest that intravenous CYC therapy may be
      more efficacious in averting ESRD and death than MMF. These results need to be
      confirmed in a larger randomized controlled trial.

PMID- 21951945
TI  - The involvement of immune semaphorins and neuropilin-1 in lupus nephritis.
AB  - BACKGROUND AND OBJECTIVES: Neuropilin-1 (NP-1), a functional vascular endothelial
      growth factor (VEGF) receptor, is important in the priming of resting T cells and
      contributes to the development of peripheral tolerance. Semaphorins, a family of
      axon guidance molecules, has been found to be involved in regulating the immune
      system. The aim of this study was to explore the involvement of NP-1 and
      semaphorins in lupus glomerulonephritis (LGN). METHODS: Twelve kidney biopsies
      from LGN patients and five normal biopsies were examined in this study. In
      addition, eight biopsies from patients with primary nephropathy and proteinuria
      were included serving as a disease control group. Biopsies were stained with anti
      VEGF, NP-1, and semaphorins. The Image Pro-Plus software was used to measure the
      intensity and extent of staining. The correlation with clinico-pathological
      parameters was evaluated. RESULTS: VEGF expression was slightly higher in LGN. NP
      1 and semaphorins were stained with significantly higher intensity in LGN when
      compared with both the normal and the disease control groups. NP-1 deposits were
      found only in damaged glomerulus areas and positively correlated with clinico
      pathological parameters of renal disease (a statistical trend). However, the
      semaphorins were found in inverse correlations. DISCUSSION: Being present in
      normal and slightly increased in diseased glomeruli, VEGF is considered
      protective during inflammation. Increased NP-1 expression in LGN may intensify
      the possible protective effect of VEGF, thereby preventing endothelial damage.
      However, one should consider the possibility that increased NP-1 expression is
      harmful and could play a role in the damage of LGN. NP-1 is suggested to be a
      reliable marker differentiating focal versus diffuse LGN. Semaphorin 3A can serve
      as a histological marker for tubular damage. The altered ability of kidneys to
      secrete semaphorins during advanced renal damage may in part explain its inverse
      correlation with renal function. Further work is needed in order to better
      understand the role of NP-1 and semaphorins in LGN.

PMID- 21951946
TI  - Two different clinical subsets of lupus hepatitis exist. Mimicking primary
      autoimmune liver diseases or part of their spectrum?

PMID- 21951947
TI  - An inside look at active transportation in Bogota: a qualitative study.
AB  - BACKGROUND: The health benefits of physical activity are well documented in
      scientific literature. Bicycling for transportation is a modality of physical
      activity that people can incorporate easily into their daily lives. METHODS: A
      qualitative study using 11 semi-structured individual interviews and 5 focus
      groups was conducted among 31 male and 13 female adult residents of Bogota,
      Colombia in 2006, to explore barriers and facilitators of bicycle use for
      transportation purposes. People were selected based on socioeconomic status, age,
      and gender. Thematic analysis complemented with thematic network analysis was
      used to analyze the data. RESULTS: Six main themes emerged from the study: 1)
      general acknowledgment of individual and collective benefits of bicycle use, 2)
      built environment conditions were linked with bicycle use, 3) some social factors
      affect bicycling negatively, 4) people perceived conflicts over public space
      related to the use of bike-paths, 5) general negative public perception of
      bicyclists, and 6) gender differences influence patterns of bicycle use.
      CONCLUSION: The findings from this qualitative study show that various social and
      physical barriers must be addressed to increase bicycle use as a means of
      transportation in Bogota.

PMID- 21951948
TI  - Binding of Sudan II and Sudan IV to bovine serum albumin: comparison studies.
AB  - In this paper, we report the interaction of Sudan II and Sudan IV to bovine serum
      albumin (BSA). Structural analysis showed that both Sudan II and Sudan IV
      interact mainly with BSA at the hydrophobic pocket and via Van der Waals forces.
      The number of bound Sudan molecule for each protein molecule was approximately 1.
      The overall binding constants at 293 K (20 degrees C) estimated for Sudan II and
      Sudan IV were 1.22 * 10(4)M(-1) and 1.48 * 10(4)M(-1), respectively. BSA backbone
      structure was damaged by the dyes with more severe phenomenon observed for Sudan
      IV. For two Sudan dyes with the same concentration, Sudan IV could cause more
      alterations on CD spectra of BSA with slight decrease of alpha-helical content
      and increase of beta-sheet content, suggesting a partial protein unfolding.

PMID- 21951949
TI  - The ecological and evolutionary implications of merging different types of
      networks.
AB  - Interactions among species drive the ecological and evolutionary processes in
      ecological communities. These interactions are effectively key components of
      biodiversity. Studies that use a network approach to study the structure and
      dynamics of communities of interacting species have revealed many patterns and
      associated processes. Historically these studies were restricted to trophic
      interactions, although network approaches are now used to study a wide range of
      interactions, including for example the reproductive mutualisms. However, each
      interaction type remains studied largely in isolation from others. Merging the
      various interaction types within a single integrative framework is necessary if
      we want to further our understanding of the ecological and evolutionary dynamics
      of communities. Dividing the networks up is a methodological convenience as in
      the field the networks occur together in space and time and will be linked by
      shared species. Herein, we outline a conceptual framework for studying networks
      composed of more than one type of interaction, highlighting key questions and
      research areas that would benefit from their study.

PMID- 21951951
TI  - Acute myeloid leukemia of donor origin after allogeneic stem cell transplantation
      from a sibling who harbors germline XPD and XRCC3 homozygous polymorphisms.
AB  - A 54-year-old woman was diagnosed with infiltrative ductal breast carcinoma. Two
      years after treatment, the patient developed an acute myeloid leukemia (AML)
      which harbored del(11q23) in 8% of the blast cells. The patient was submitted for
      allogeneic stem cell transplantation (aSCT) from her HLA-compatible sister. Ten
      months after transplantation, she relapsed with an AML with basophilic maturation
      characterized by CD45(low) CD33(high), CD117+, CD13(-/+), HLA Dr(high),
      CD123(high), and CD203c+ blast cells lacking expression of CD7, CD10, CD34, CD15,
      CD14, CD56, CD36, CD64, and cytoplasmic tryptase. Karyotype analysis showed the
      emergence of a new clone with t(2;14) and FISH analysis indicated the presence of
      MLL gene rearrangement consistent with del(11q23). Interestingly, AML blast cell
      DNA tested with microsatellite markers showed the same pattern as the donor's,
      suggesting that this AML emerged from donor cells. Additionally, polymorphisms of
      the XPA, XPD, XRCC1, XRCC3 and RAD51 DNA repair genes revealed three unfavorable
      alleles with low DNA repair capacity.In summary, we report the first case of AML
      involving XPD and XRCC3 polymorphisms from donor origin following allogeneic stem
      cell transplantation and highlight the potential need for careful analysis of DNA
      repair gene polymorphisms in selecting candidate donors prior to allogeneic stem
      cell transplantation.

PMID- 21951952
TI  - A comprehensive strategy for dementia from primary prevention to end-stage
      management.

PMID- 21951953
TI  - CAMTA1 T polymorphism is associated with neuropsychological test performance in
      older adults with cardiovascular disease.
AB  - BACKGROUND: Cardiovascular disease has long been associated with poor
      neurocognitive outcome, with multiple pathophysiological mechanisms that are
      linked to cognitive impairment in older adults. Although less frequently
      examined, insulin dysregulation is known to affect vascular function and the
      associated brain dysfunction in cardiovascular disease. Accordingly, genetic
      factors tied to insulin regulation may make certain people with cardiovascular
      disease more susceptible to cognitive dysfunction. Specifically, the calmodulin
      binding transcription activator 1 (CAMTA1) genotype, which has been examined as a
      risk factor for Type 2 diabetes and has been linked to reduced episodic memory
      performance in healthy young adults, is a potential candidate gene. METHODS:
      Blood samples were obtained from 113 older adults with cardiovascular disease who
      also underwent neuropsychological testing. Carriers of either one or two copies
      of the T allele of CAMTA1 were categorized into one group (n = 63), whereas non
      carriers were categorized into a second group (n = 50). RESULTS: Analyses showed
      that carriers of the T allele performed more poorly on tests of attention,
      executive function, and psychomotor speed, but not on tests of memory. Carriers
      of the T allele also performed more poorly on a measure of global cognitive
      function. CONCLUSIONS: Results indicate that CAMTA1 genotype is associated with
      cognitive function in older adults with cardiovascular disease, because carriers
      of the T allele performed more poorly on tests of attention, executive function,
      and psychomotor speed. Contrary to expectations, there were no differences in
      memory performance among carriers and non-carriers of the T allele. Given these
      mixed findings, further studies are necessary to elucidate the association
      between CAMTA1 and cognition, particularly gene expression and neuroimaging
      studies.

PMID- 21951954
TI  - Association between brain-derived neurotrophic factor (BDNF) gene polymorphisms
      and executive function in Japanese patients with Alzheimer's disease.
AB  - BACKGROUND: To address the functional roles of genetic polymorphisms of brain
      derived neurotrophic factor (BDNF) in Alzheimer's disease (AD) from a
      neuropsychological aspect, we used a cross-sectional study design to investigate
      the association between novel single nucleotide polymorphisms (SNPs) of the BDNF
      gene (Val66Met (G196A) and C270T) and the Frontal Assessment Battery (FAB) score,
      which reflects executive function as a non-memory cognitive impairment. METHODS:
      One hundred and sixty-nine outpatients with AD or amnestic mild cognitive
      impairment (A-MCI) were recruited to the study and divided into three genotypic
      groups for each representative BDNF functional polymorphism as follows: (i)
      Val66Met (G196A): G/G (n = 45), G/A (n = 104), and A/A (n = 20); and (ii) C270T:
      C/C (n = 160), C/T (n = 9), and T/T (n = 0). Then, age, sex ratio, duration of
      illness (months), education years, Mini-Mental State Examination (MMSE) score,
      behavioral pathology in Alzheimer disease (Behave-AD) score, Clinical Dementia
      Rating (CDR) ratio, and total and subtest FAB scores were compared between the
      genotypic groups for each SNP. RESULTS: Significant differences were found in the
      total (P < 0.01) and subtest (conflicting instructions and prehension behavior; P
      < 0.01) FAB scores between the C270T polymorphism groups (C/C and C/T), but not
      among the G196A polymorphism groups. However, no significant differences in age,
      sex ratio, duration of illness (months), education years, Behave-AD score, CDR
      ratio, or MMSE score (reflecting attention and memory function) were found
      between the individual polymorphism genotypes (G196A and C270T). CONCLUSION: Of
      the known BDNF polymorphisms, the C270T SNP may influence executive dysfunction
      as a non-memory cognitive impairment in Japanese patients with AD.

PMID- 21951955
TI  - Polypharmacy increases the risk of Parkinson's disease in older people in Taiwan:
      a population-based study.
AB  - BACKGROUND: Little is known about the relationship between polypharmacy and
      Parkinson's disease (PD). In the present study, we tested the hypothesis that
      polypharmacy increases the risk of PD in older people in Taiwan. METHODS: From a
      randomly sampled cohort of one million health insurance enrollees, we identified
      2827 new cases of PD over the period 2000-2008 aged >= 65 years and selected 11
      308 age-matched controls without PD. Medication history and baseline
      comorbidities were compared between the two groups. We defined 'polypharmacy' as
      an average daily use of five or more prescribed drugs. RESULTS: Compared with
      patients using between none and one drug, the odds ratios (ORs) for PD increased
      to 1.53, 2.08, 2.64, and 2.95 for patients using two to four, five to seven,
      eight to nine, and >= 10 drugs, respectively. The other conditions associated
      with PD were dementia (OR 3.43), stroke (OR 2.30), depression (OR 2.15), and
      alcoholism (OR 2.11). Hyperlipidemia (OR 0.90) was inversely associated with PD.
      CONCLUSIONS: Polypharmacy was shown to increase the risk of PD in older people in
      Taiwan, with risk increasing with the number of medications taken daily.
      Dementia, stroke, depression, and alcoholism were also associated with an
      increased risk of PD, whereas there was an inverse correlation between PD and
      hyperlipidemia.

PMID- 21951956
TI  - Dementia with Lewy bodies is associated with higher scores on the Geriatric
      Depression Scale than is Alzheimer's disease.
AB  - BACKGROUND: Several reports suggest a higher morbidity of depression in patients
      with dementia with Lewy bodies (DLB) than in patients with Alzheimer's disease
      (AD). However, these results have not been duplicated consistently. The
      psychiatric symptoms of dementia, including depression, are important for its
      diagnosis and management. Thus, the aim of the present study was to clarify the
      characteristics of the depressive symptoms in DLB compared with AD using the
      Geriatric Depression Scale (GDS). METHODS: We examined the GDS score for 86
      patients with probable DLB (based on the Consensus Criteria for the clinical
      diagnosis of DLB) and 86 patients with probable 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
      according to age, sex, education, and Mini-Mental State Examination (MMSE)
      scores. We also examined correlations between GDS scores and age, sex, or MMSE
      scores in both groups. Correlations between GDS scores and
      metaiodobenzylguanidine (MIBG) scintigraphy were examined in patients with DLB.
      To characterize the GDS in DLB, its profile was examined using factor structures.
      RESULTS: Scores for DLB patients were twice as high on the GDS as those for AD
      patients. There was no correlation between GDS score and age, sex, or MMSE scores
      in either group. Furthermore, there was no correlation between the results of
      MIBG scintigraphy and GDS scores in the DLB group. Using factor structures, the
      depression symptom profile of these diseases suggested that depression-specific
      symptoms, such as mood, worry, or future outlook, were more frequent in the DLB
      group than non-specific symptoms, such as lack of energy, decreased
      concentration, or apathy. CONCLUSIONS: The data suggest that depressive symptoms
      are highly specific symptoms of DLB, independent of other features of this
      disorder. The GDS could be used as a subsidiary tool in differentiating DLB from
      AD and is more useful than clinical observations of depression.

PMID- 21951958
TI  - Presenile dementia diagnosed as posterior cortical atrophy.
AB  - Posterior cortical atrophy (PCA) was originally proposed in 1988 based on five
      cases of dementia presenting characteristic clinical symptoms. The concept of PCA
      is still not generally accepted. Herein, we present a case of a presenile female
      with PCA. A 57-year-old woman was brought to the hospital by her older sister.
      The patient's chief complaints were that she could not drive a car safely and had
      caused numerous traffic accidents. Construction apraxia and unilateral spatial
      agnosia were detected by neuropsychological tests. The patient could not write a
      coherent the letter even though she was well educated. In addition, she
      demonstrated slight memory disturbance and she needed her sister's support in
      daily life. Magnetic resonance imaging and single photon emission computed
      tomography examinations confirmed bilateral posterior atrophy and significant
      hypoperfusion in the occipital regions. The neuropathological background of PCA
      remains unclear. Therefore, the concept of PCA should be validated by the
      accumulation of information from more cases.

PMID- 21951957
TI  - Parkinsonism with multiple cysts in the bilateral striata.
AB  - The present paper reports on a 68-year-old man with a 10-year history of
      parkinsonism who developed hallucinations and delusions after admission to an
      intensive care unit for the treatment of organophosphate intoxication. His
      initial diagnosis was delirium. On the basis of brain computed tomography
      findings and clinical symptoms, we diagnosed drug-induced psychosis in
      parkinsonism with multiple cysts in the bilateral striata.

PMID- 21951959
TI  - Depression-dementia medius: between depression and the manifestation of dementia
      symptoms.
AB  - Depression and dementia, among the most common conditions in clinical practice,
      sometimes coexist, sometimes succeed each other, and often confuse clinicians. In
      the present paper, the clinical concept of 'depression-dementia medius' (which
      includes pseudodementia and depression in Alzheimer's disease as exemplars) is
      proposed, in reference to Janet's concept of psychological tension. Because
      psychosomatically complex human lives are always in a state of dynamic
      equilibrium, it seems sensible to propose that pseudodementia and depression in
      Alzheimer's disease are located within a spectrum extending from depression
      without dementia symptoms to dementia without depression. From the Janetian
      viewpoint, pseudodementia is regarded as uncovered latent dementia as a result of
      reduced psychological tension. Dementia is more than a fixed progressive
      condition under this view, and is a manifestation of dynamic mental activities.
      Characterizing these entities through perspectives such as psychological tension
      may yield deep insights in clinical practice.

PMID- 21951960
TI  - Exploring strategies to alleviate caregiver burden: effects of the National Long
      Term Care insurance scheme in Japan.
AB  - The ever-increasing population of older people with disabilities, including
      dementia, has been accompanied by a corresponding growth in the number of family
      caregivers, who are themselves at risk of developing mental and physical health
      problems. As a result, the need for practical and effective approaches for
      alleviating caregiver burden has become a major public health concern. One
      approach involves the development of public policy initiatives to allow the
      caregiver burden to be borne partly by society as a whole, rather than falling
      solely on individuals. In 2000, Japan introduced a National Long-Term Care (LTC)
      insurance scheme that requires adults over the age of 40 years to pay compulsory
      monthly premiums, with one aim of the program being to reduce caregiver burden.
      The present paper reviews the effects of this scheme on caregivers' and the
      general public's perception of caregiver burden and assesses what other measures
      are needed to further reduce and/or prevent burden. Drawing on recent studies,
      four questions are addressed: (i) have caregivers' attitudes towards caregiving
      changed since the implementation of the scheme; (ii) do services provided under
      the scheme alleviate caregiver burden; (iii) what are the general public's
      attitudes to and understanding of family caregiving; and (iv) what is the general
      public's level of understanding of dementia? Results from recent studies suggest
      that the LTC insurance scheme in Japan appears to be an effective measure for
      alleviating the burden of caregiving among current family caregivers, but larger
      studies are needed to determine overall effectiveness.

PMID- 21951961
TI  - Localization of seed oil body proteins in tobacco protoplasts reveals specific
      mechanisms of protein targeting to leaf lipid droplets.
AB  - Oleosin, caleosin and steroleosin are normally expressed in developing seed cells
      and are targeted to oil bodies. In the present work, the cDNA of each gene tagged
      with fluorescent proteins was transiently expressed into tobacco protoplasts and
      the fluorescent patterns observed by confocal laser scanning microscopy. Our
      results indicated clear differences in the endocellular localization of the three
      proteins. Oleosin and caleosin both share a common structure consisting of a
      central hydrophobic domain flanked by two hydrophilic domains and were correctly
      targeted to lipid droplets (LD), whereas steroleosin, characterized by an N
      terminal oil body anchoring domain, was mainly retained in the endoplasmic
      reticulum (ER). Protoplast fractionation on sucrose gradients indicated that both
      oleosin and caleosin-green fluorescent protein (GFP) peaked at different
      fractions than where steroleosin-GFP or the ER marker binding immunoglobulin
      protein (BiP), were recovered. Chemical analysis confirmed the presence of
      triacylglycerols in one of the fractions where oleosin-GFP was recovered.
      Finally, only oleosin- and caleosin-GFP were able to reconstitute artificial oil
      bodies in the presence of triacylglycerols and phospholipids. Taken together, our
      results pointed out for the first time that leaf LDs can be separated by the ER
      and both oleosin or caleosin are selectively targeted due to the existence of
      selective mechanisms controlling protein association with these organelles.

PMID- 21951962
TI  - In vitro susceptibility to pyrimethamine of DHFR I164L single mutant Plasmodium
      falciparum.
AB  - BACKGROUND: Recently, Plasmodium falciparum parasites bearing Pfdhfr I164L single
      mutation were found in Madagascar. These new mutants may challenge the use of
      antifolates for the intermittent preventive treatment of malaria during pregnancy
      (IPTp). Assays with transgenic bacteria suggested that I164L parasites have a
      wild-type phenotype for pyrimethamine but it had to be confirmed by testing the
      parasites themselves. METHODS: Thirty Plasmodium falciparum clinical isolates
      were collected in 2008 in the south-east of Madagascar. A part of Pfdhfr gene
      encompassing codons 6 to 206 was amplified by PCR and the determination of the
      presence of single nucleotide polymorphisms was performed by DNA sequencing. The
      multiplicity of infection was estimated by using an allelic family-specific
      nested PCR. Isolates that appeared monoclonal were submitted to culture
      adaptation. Determination of IC(50s) to pyrimethamine was performed on adapted
      isolates. RESULTS: Four different Pfdhfr alleles were found: the 164L single
      mutant-type (N = 13), the wild-type (N = 7), the triple mutant-type 51I/59R/108N
      (N = 9) and the double mutant-type 108N/164L (N = 1). Eleven out 30 (36.7%) of P.
      falciparum isolates were considered as monoclonal infection. Among them, five
      isolates were successfully adapted in culture and tested for pyrimethamine in
      vitro susceptibility. The wild-type allele was the most susceptible with a 50%
      inhibitory concentration (IC(50)) < 10 nM. The geometric mean of IC(50) of the
      three I164L mutant isolates was 6-fold higher than the wild-type with 61.3 nM (SD
      = 3.2 nM, CI95%: 53.9-69.7 nM). These values remained largely below the IC(50) of
      the triple mutant parasite (13,804 nM). CONCLUSION: The IC(50)s of the I164L
      mutant isolates were significantly higher than those of the wild-type (6-fold
      higher) and close from those usually reported for simple mutants S108N (roughly10
      fold higher than wild type). Given the observed values, the determination of
      IC(50)s directly on parasites did not confirm what has been found on transgenic
      bacteria. The prevalence increase of the Pfdhfr I164L single mutant parasite
      since 2006 could be explained by the selective advantage of this allele under
      sulphadoxine-pyrimethamine pressure. The emergence of highly resistant alleles
      should be considered in the future, in particular because an unexpected double
      mutant-type allele S108N/I164L has been already detected.

PMID- 21951963
TI  - Celastrol-induced apoptosis in human HaCaT keratinocytes involves the inhibition
      of NF-kappaB activity.
AB  - Psoriasis is a chronic inflammatory skin disease affecting 1-3% of the world's
      population. Traditional Chinese medicines have been extensively used for treating
      psoriasis with promising clinical results. Celastrol, a triterpenoid isolated
      from a Chinese herb Celastrus orbiculatus caulis, has been known to have diverse
      pharmacological effects such as anti-inflammatory, anti-cancer and antioxidant
      activities. The present study aimed at evaluating the anti-proliferative action
      of celastrol on cultured HaCaT cells and elucidating the mechanisms of action
      involved. Celastrol was shown to inhibit HaCaT cells growth with an IC50 value of
      1.1 MUM as measured by MTT assay. The ability of celastrol to induce apoptosis
      was studied by flow cytometric and western blot analyses. Celastrol was found to
      be capable of inducing apoptosis in HaCaT cells as characterized by phosphatidyl
      serine (PS) externalization, depolarization of mitochondrial membrane potential
      and activation of caspase-3. The apoptosis induced by celastrol could be
      suppressed by Z-IETD-FMK and Z-LEHD-FMK, the respective caspase-8 and caspase-9
      inhibitor. In addition, western blot analysis revealed a significant augmentation
      in the protein expression of Bax and attenuation in Bcl-2, suggesting that the
      celastrol-induced apoptosis acts through both death receptor and mitochondrial
      pathways. Moreover, western blot analysis on the expression of Rel/NF-kappaB
      demonstrated that the celastrol-mediated apoptosis on HaCaT cells was associated
      with the inhibition of the NF-kappaB pathway. Taken together, the present project
      has for the first time identified celastrol as a naturally occurring compound
      with potent apoptogenic action on cultured human keratinocytes, rendering it a
      promising candidate for further development into an anti-psoriatic agent.

PMID- 21951964
TI  - Acute myocardial ischemia directly modulates the expression of brain natriuretic
      peptide at the transcriptional and translational levels via inflammatory
      cytokines.
AB  - Cardiomyocyte stretching has been reported to be a major trigger for brain
      natriuretic peptide (BNP) release; however, an increase in circulating BNP is
      observed in patients with acute myocardial ischemia in the absence of increased
      left ventricular wall stress or cardiomyocyte stretching. In the present study,
      to investigate the direct and independent effects of acute myocardial ischemia on
      BNP expression and its mechanism, we established an in vitro glucose-free
      ischemia and hypoxia injured model of cultured rat cardiomyotes and proved
      hypoxia upregulated expressions of interleukin-6(il-6) and BNP. Further treatment
      with il-6 elicited dose- and time-dependent increases in BNP mRNA and protein
      expression as well as an upregulation in transforming growth factor-beta1 (TGF
      beta1)/Smad2 expression, which was partially suppressed by a neutralizing
      antibody. In conclusion, our study showed that acute myocardial ischemia can
      directly upregulate BNP expression at the translational and transcriptional
      levels through the action of il-6, and this process is associated with the
      upregulation of TGF-beta1/Smad2 signal path.

PMID- 21951965
TI  - Peripheral inflammation alters desensitization of substance P-evoked current in
      rat dorsal root ganglion neurons.
AB  - The neuropeptide substance P is synthesized in a proportion of neurons of the
      peripheral and central nervous system, and the receptor for substance P,
      tachykinin NK1 receptor, has been identified in numerous areas of the central
      nervous system including the spinal cord. The present investigation was to
      confirm the existence of tachykinin NK1 receptor on rat dorsal root ganglion
      (DRG) neurons and characterize the adaptation of inward current evoked by
      substance P during carrageenan-induced peripheral inflammation. Using whole-cell
      voltage recording technique, our results demonstrated that 1 MUM substance P
      elicited significant inward current in a small population of small-diameter DRG
      neurons of control rats (7%, n=218) and in a bigger proportion of DRG neurons of
      carrageenan-inflamed rats (15%, n=203). Desensitization of substance P-evoked
      current was exhibited in almost all of substance P-responsive DRG neurons in
      control rats (94%, n=16), while it diminished in a bigger proportion of DRG
      neurons (35%, n=31) in inflamed rats. Furthermore, desensitization of substance P
      evoked current was recovered by the activation of protein kinase C (PKC) by
      application of phorbol 12,13-dibutyrate, a selective agonist of PKC, in the DRG
      neurons of the inflamed rats. All these results indicated that tachykinin NK1
      receptor in the primary afferents might contribute to the development and
      maintenance of inflammatory pain.

PMID- 21951966
TI  - Geissoschizine methyl ether has third-generation antipsychotic-like actions at
      the dopamine and serotonin receptors.
AB  - Aripiprazole has made a significant contribution to the treatment of
      schizophrenia and related disorders. It has improved its safety and tolerability
      profiles, and these effects have been attributed to its pharmacological profile
      at the serotonin 5-HT and dopamine D(2) receptors. To discover compounds that
      have a similar pharmacological profile, we introduced a generic single-cell-based
      calcium imaging assay that standardizes the readouts from various assays used in
      previous studies on aripiprazole. In the present assay, the efficacy and potency
      of known ligands of serotonin 5-HT(1A), 5-HT(2A), 5-HT(2C), 5-HT(7) and dopamine
      D(2L) receptors were comparable to those found in previous studies using a
      variety of readouts. The developed assay was also able to reproduce the partial
      agonist activity, the low intrinsic activity and the selective activation of
      aripiprazole at the dopamine D(2L) receptors. Under identical experimental
      conditions, geissoschizine methyl ether (GM), a plant indole alkaloid, behaved as
      a partial agonist at the serotonin 5-HT(1A) receptor, a partial
      agonist/antagonist at the dopamine D(2L) receptor and an antagonist at the
      serotonin 5-HT(2A), 5-HT(2C) and 5-HT(7) receptors. Interestingly, GM showed a
      relatively low intrinsic activity and evoked a partial activation response in a
      subset of cells expressing the dopamine D(2L) receptor; both of these effects
      were similarly observed for aripiprazole. Although GM is far less potent at the
      dopamine receptor than aripiprazole at dopamine D(2L) receptors (EC(50)=4.4 MUM
      for GM vs. EC(50)=56 nM for aripiprazole), GM and GM derivatives may comprise a
      new set of candidates for atypical antipsychotics.

PMID- 21951967
TI  - 1-(5-bromo-2-hydroxy-4-methoxyphenyl)ethanone [SE1] suppresses pro-inflammatory
      responses by blocking NF-kappaB and MAPK signaling pathways in activated
      microglia.
AB  - Unregulated activation of microglia is a key risk factor contributes to
      neurodegenerative diseases and suppression of this phenomenon is considered as a
      potential therapeutic target. The compound isolated from sea horse Hippocampus
      kuda Bleeler; 1-(5-bromo-2-hydroxy-4-methoxyphenyl)ethanone [SE1] was
      characterized for its ability in suppressing LPS mediated activation of murine BV
      2 cells. Despite the presence of various active molecular groups in the
      structure, SE1 has not well explored for its biological activities. The outcome
      of this study clearly indicated that SE1 inhibited the production of inflammatory
      mediators; nitric oxide, prostaglandin E(2) and pro-inflammatory cytokines.
      Furthermore, it inhibited the protein and gene expression levels of inducible
      nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-alpha, interleukin
      1beta and interleukin-6. The responsible signaling mechanisms leading to these
      inhibitions were identified as SE1 mediated blocking of phosphorylation of
      mitogen activate protein kinase (MAPK) molecules; C-jun-N-terminal kinase (JNK),
      p38 and nuclear translocation of nuclear factor-kappaB (NF-kappaB) p65 and p50
      subunits. These results suggest that SE1 has the potential to be further
      developed as therapeutic against neuro-inflammation.

PMID- 21951969
TI  - Long circulating chitosan/PEG blended PLGA nanoparticle for tumor drug delivery.
AB  - Polymeric nanoparticles have long been sought after as carriers for systemic and
      targeted drug delivery. The ability of these particles to circulate in the
      bloodstream for a prolonged period of time is often a prerequisite for successful
      targeted delivery. To achieve this, paclitaxel loaded chitosan and polyethylene
      glycol coated PLGA (PLGA-CS-PEG) nanoparticles were formulated and characterized
      that could efficiently encapsulate hydrophobic drugs, and also evade the
      phagocytic uptake by reducing opsonization by blood proteins, hence increasing
      the bioavailability of the drug. In our study, we primarily assessed a rational
      approach for designing and formulating ideal long-circulating nanoparticles by
      optimizing the concentration of chitosan (CS) and polyethylene glycol (PEG).
      Uptake efficiency and in vitro cytotoxicity of the formulated nanoparticles was
      also evaluated in different cancer cell lines (retinoblastoma, breast cancer and
      pancreatic cancer). PLGA-CS-PEG nanoparticles showed dramatic prolongation in
      blood circulation, as well as reduced macrophage uptake, with only a small amount
      of the nanoparticles sequestered in the liver, when compared to PLGA-CS and PLGA
      nanoparticles. Superior anti-proliferative effect and cell cycle inhibition was
      observed in case of PLGA-CS nanoparticles and PLGA-CS-PEG nanoparticles over PLGA
      nanoparticles and native paclitaxel, which may be due to higher cellular uptake
      resulting in greater antiproliferative activity of nanoparticles. The present
      results thus suggest that, a combinational coating of PEG and chitosan may
      represent a significant step in the development of long-circulating drug delivery
      carriers for tumor drug delivery.

PMID- 21951970
TI  - Economic burden and cost determinants of deep vein thrombosis during 2 years
      following diagnosis: a prospective evaluation.
AB  - BACKGROUND: Few studies have evaluated the long-term economic consequences of
      deep vein thrombosis (DVT). None of them have incorporated prospectively
      collected clinical data to ensure accurate identification of incident cases of
      DVT and DVT-related health outcomes of interest, such as post-thrombotic syndrome
      (PTS). OBJECTIVES: To prospectively quantify medical and non-medical resource use
      and costs related to DVT during 2 years following diagnosis, and to identify
      clinical determinants of costs. METHODS: Three hundred and fifty-five consecutive
      patients with acute DVT were recruited at seven Canadian hospital centers.
      Resource use and cost information were retrieved from three sources: weekly
      patient-completed cost diaries, nurse-completed case report forms, and the Quebec
      provincial administrative healthcare database (RAMQ). RESULTS: The rate of DVT
      related hospitalization was 3.5 per 100 patient-years (95% confidence interval
      [CI] 2.2-4.9). Patients reported a mean (standard deviation) of 15.0 (14.5)
      physician visits and 0.7 (1.2) other healthcare professional visits. The average
      cost of DVT was $5180 (95% CI $4344-6017) in Canadian dollars, with 51.6% of
      costs being attributable to non-medical resource use. Multivariate analysis
      identified four independent predictors of costs: concomitant pulmonary embolism
      (relative increase in cost [RIC] 3.16; 95% CI 2.18-4.58), unprovoked DVT (RIC
      1.65; 95% CI 1.28-2.13), development of PTS during follow-up (RIC 1.35; 95% CI
      1.05-1.74), and management of DVT in the inpatient setting (RIC 1.79; 95% CI 1.33
      2.40). CONCLUSIONS: The economic burden of DVT is substantial. The use of
      measures to prevent the occurrence of PTS and favoring outpatient care of DVT has
      the potential to diminish costs.

PMID- 21951968
TI  - Activation of group I mGlu receptors contributes to facilitation of NMDA receptor
      membrane current in spinal dorsal horn neurons after hind paw inflammation in
      rats.
AB  - The interaction between the group I metabotropic glutamate (mGlu) receptors and N
      methyl-D-aspartate (NMDA) receptors plays a critical role in spinal
      hyperexcitability and hyperalgesia. The cellular mechanisms underlying this
      interaction remain unknown. Utilizing an ex vivo spinal slice preparation from
      young adult rats, we investigated the group I mGlu receptor modulation of NMDA
      receptor-mediated current in superficial dorsal horn neurons by patch clamp
      recording after complete Freund's adjuvant (CFA)-induced hind paw inflammation.
      We show that NMDA receptor-mediated dorsal root stimulation-evoked EPSC (eEPSC)
      and NMDA-induced current was enhanced in the inflamed rats, compared to naive
      rats and this effect was attenuated by AIDA (1 mM), a group I mGlu receptor
      antagonist. There were also increases in the frequency and amplitude of miniature
      excitatory postsynaptic currents in the presence of tetrodotoxin, suggesting
      enhanced presynaptic glutamate release probability and postsynaptic membrane
      responsiveness in inflamed rats. DHPG (10 MUM), a selective group I mGlu receptor
      agonist, further facilitated NMDA receptor-mediated eEPSC and NMDA-induced
      current in inflamed rats. The DHPG-produced facilitation of NMDA-induced current
      was blocked by intracellular dialysis of GDP-beta-S (1 mM), a G protein
      antagonist, and BAPTA (15 mM), an intracellular calcium chelating agent; and by
      pretreatment with U73,122 (10 MUM), a PLC inhibitor, or 2-APB (100 MUM), an IP3
      receptor antagonist. These findings support the hypothesis that signal
      transduction coupling between group I mGlu receptors and NMDA receptors underlies
      the activation of NMDA receptors in spinal hyperexcitability and hyperalgesia.

PMID- 21951971
TI  - Association of methylenetetrahydrofolate reductase C677T-A1298C polymorphisms
      with risk for esophageal adenocarcinoma, Barrett's esophagus, and reflux
      esophagitis.
AB  - Incidence of the esophagus adenocarcinoma has been dramatically increasing in
      Western countries since the last decade. Gastroesophageal reflux disease and
      Barrett's esophagus are risk factors for adenocarcinoma.
      Methylenetetrahydrofolate reductase (MTHFR) genes play a key role not only in
      folate metabolism but also in esophagus, stomach, pancreatic carcinoma, and acute
      leukemias. Studies have suggested that genetic polymorphisms of MTHFR (C677T) may
      clarify the causes and events involved in esophageal carcinogenesis. In this
      study, we evaluated MTHFR C677T and A1298C polymorphisms, and vitamin B12,
      folate, and plasma homocystein levels in patients with esophageal adenocarcinoma
      (EAC), Barrett's esophagus (BE), chronic esophagitis, and healthy controls (n =
      26, n = 14, n = 30, and n = 30, respectively). The mean age of patients in the
      EAC and BE groups was significantly higher compared with the control group (P <
      0.001, P = 0.003, respectively). In all patient groups, serum folate levels were
      significantly lower than that of the control group (P < 0.01, P < 0.05, and P <
      0.01, respectively). There was no statistically significant association between
      folate levels and MTHFR gene polymorphisms. No differences were found in terms of
      MTHFR gene polymorphisms, homocystein, and B12 levels among the groups. MTHFR
      gene polymorphisms and folate deficiency are not predictors of early esophageal
      carcinoma. However, further studies using larger series of patients are needed to
      evaluate the effect of genetic polymorphisms in the folate metabolic pathway and
      to clarify the role of folate deficiency and folate metabolism in the development
      of esophagus adenocarcinoma.

PMID- 21951972
TI  - Percutaneous transtracheal jet ventilation.

PMID- 21951974
TI  - Anti-hypoalbuminemic effect of branched-chain amino acid granules in patients
      with liver cirrhosis is independent of dietary energy and protein intake.
AB  - AIM:   A multicenter prospective intervention study was conducted in 204 patients
      with uncompensated liver cirrhosis to explore the influence of dietary intake and
      patient clinical characteristics on improvement of hypoalbuminemia at weeks 12
      and 24 of treatment with branched-chain amino acid (BCAA) granules. METHODS:  
      The primary endpoint set in this study was improvement of hypoalbuminemia in
      patients with liver cirrhosis. The dietary energy and protein intake per day were
      estimated based on the results of a survey on diet during a 3-day period
      preceding the start of the study. RESULTS:   As for the primary endpoint, the
      mean serum albumin level increased significantly at weeks 12 and 24 of BCAA
      treatment, compared with the baseline level. The mean Child-Pugh score decreased
      significantly at weeks 12 and 24 of treatment as compared to the mean baseline
      score. There was a significant increase in the serum albumin level following
      treatment with BCAA granules regardless of energy intake and of protein intake.
      The incidence of ascites and edema significantly decreased in the overall patient
      population both at weeks 12 and 24 of treatment, compared with the baseline
      incidence. A subgroup analysis conducted in patients stratified according to
      changes in the serum albumin level at week 12 of treatment as against baseline
      showed that the incidence of ascites/edema was significantly reduced not only in
      the increased albumin group but in the unchanged albumin group. CONCLUSION:   The
      present data suggest that the anti-hypoalbuminemic effect of BCAA treatment in
      patients with liver cirrhosis is independent of dietary intake.

PMID- 21951973
TI  - Enteroaggregative Escherichia coli promotes transepithelial migration of
      neutrophils through a conserved 12-lipoxygenase pathway.
AB  - Enteroaggregative Escherichia coli (EAEC) induces release of pro-inflammatory
      markers and disruption of intestinal epithelial barriers in vitro, suggesting an
      inflammatory aspect to EAEC infection. However, the mechanisms underlying EAEC
      induced mucosal inflammatory responses and the extent to which these events
      contribute to pathogenesis is not well characterized. Employing an established in
      vitro model we demonstrated that EAEC prototype strain 042 induces migration of
      polymorphonuclear neutrophils (PMNs) across polarized T84 cell monolayers. This
      event was mediated through a conserved host cell signalling cascade involving the
      12/15-LOX pathway and led to apical secretion of an arachidonic acid-derived
      lipid PMN chemoattractant, guiding PMNs across the epithelia to the site of
      infection. Moreover, supporting the hypothesis that inflammatory responses may
      contribute to EAEC pathogenesis, we found that PMN transepithelial migration
      promoted enhanced attachment of EAEC 042 to T84 cells. These findings suggest
      that EAEC-induced PMN infiltration may favour colonization and thus pathogenesis
      of EAEC.

PMID- 21951975
TI  - Toll-like receptor 2 contributes to chemokine gene expression and macrophage
      infiltration in the dorsal root ganglia after peripheral nerve injury.
AB  - BACKGROUND: We have previously reported that nerve injury-induced neuropathic
      pain is attenuated in toll-like receptor 2 (TLR2) knock-out mice. In these mice,
      inflammatory gene expression and spinal cord microglia actvation is compromised,
      whereas the effects in the dorsal root ganglia (DRG) have not been tested. In
      this study, we investigated the role of TLR2 in inflammatory responses in the DRG
      after peripheral nerve injury. RESULTS: L5 spinal nerve transection injury
      induced the expression of macrophage-attracting chemokines such as CCL2/MCP-1 and
      CCL3/MIP-1 and subsequent macrophage infiltration in the DRG of wild-type mice.
      In TLR2 knock-out mice, however, the induction of chemokine expression and
      macrophage infiltration following nerve injury were markedly reduced. Similarly,
      the induction of IL-1beta and TNF-alpha expression in the DRG by spinal nerve
      injury was ameliorated in TLR2 knock-out mice. The reduced inflammatory response
      in the DRG was accompanied by attenuation of nerve injury-induced spontaneous
      pain hypersensitivity in TLR2 knock-out mice. CONCLUSIONS: Our data show that
      TLR2 contributes to nerve injury-induced proinflammatory chemokine/cytokine gene
      expression and macrophage infiltration in the DRG, which may have relevance in
      the reduced pain hypersensitivity in TLR2 knock-out mice after spinal nerve
      injury.

PMID- 21951976
TI  - UK research expenditure on dementia, heart disease, stroke and cancer: are levels
      of spending related to disease burden?
AB  - BACKGROUND AND PURPOSE: A UK government review recommended that the impact of
      disease on the population and economy should be assessed to inform health
      research priorities. This study aims to quantify UK governmental and charity
      research funding for dementia, cancer, coronary heart disease (CHD) and stroke in
      2007/08 and assess whether the levels of research expenditure are aligned with
      disease and economic burden. METHODS: We identified UK governmental agencies and
      charities providing health research funding and determined their levels of
      funding for dementia, cancer, CHD and stroke. Research funding levels were
      compared to the number of cases, disability-adjusted life years (DALYs) and
      economic burden. Economic costs were estimated using data on morbidity,
      mortality, health and social care use, private costs and other related
      indicators. RESULTS: Research funding to the four diseases was L833 million, of
      which L590 million (71%) was devoted to cancer, L169 million (20%) to CHD, L50
      million (6%) to dementia and L23 million (4%) to stroke. Cancer received L482 in
      research funding per 1000 DALYs lost, CHD received L266, dementia received L166,
      with stroke receiving L71. In terms of economic burden, for every L1 million of
      health and social care costs attributable to each disease, cancer received L129
      269 in research funding, CHD received L73 153, stroke received L8745 and dementia
      received L4882. CONCLUSIONS: Most health research funding in the UK is currently
      directed towards cancer. When compared to their burden, our analysis suggests
      that research spending on dementia and stroke is severely underfunded in
      comparison with cancer and CHD.

PMID- 21951977
TI  - Ocular pulse amplitude measured by PASCAL dynamic contour tonometry in patients
      with a cavernous sinus dural arteriovenous fistula.

PMID- 21951978
TI  - Insulin-like growth factor binding protein-2: NMR analysis and structural
      characterization of the N-terminal domain.
AB  - The insulin-like growth factor binding proteins are a family of six proteins
      (IGFBP-1 to -6) that bind insulin-like growth factors-I and -II (IGF-I/II) with
      high affinity. In addition to regulating IGF actions, IGFBPs have IGF-independent
      functions. IGFBP-2, the largest member of this family, is over-expressed in many
      cancers and has been proposed as a possible target for the development of novel
      anti-cancer therapeutics. The IGFBPs have a common architecture consisting of
      conserved N- and C-terminal domains joined by a variable linker domain. The
      solution structure and dynamics of the C-terminal domain of human IGFBP-2 have
      been reported (Kuang Z. et al. J. Mol. Biol. 364, 690-704, 2006) but neither the
      N-domain (N-BP-2) nor the linker domain have been characterised. Here we present
      NMR resonance assignments for human N-BP-2, achieved by recording spectra at low
      protein concentration using non-uniform sampling and maximum entropy
      reconstruction. Analysis of secondary chemical shifts shows that N-BP-2 possesses
      a secondary structure similar to that of other IGFBPs. Although aggregation
      hampered determination of the solution structure for N-BP-2, a homology model was
      generated based on the high degree of sequence and structure homology exhibited
      by the IGFBPs. This model was consistent with experimental NMR and SAXS data and
      displayed some unique features such as a Pro/Ala-rich non-polar insert, which
      formed a flexible solvent-exposed loop on the surface of the protein opposite to
      the IGF-binding interface. NMR data indicated that this loop could adopt either
      of two alternate conformations in solution - an entirely flexible conformation
      and one containing nascent helical structure. This loop and an adjacent poly
      proline sequence may comprise a potential SH3 domain interaction site for binding
      to other proteins.

PMID- 21951979
TI  - Synthesis of lipophosphoramidyl-cyclodextrins and their supramolecular
      properties.
AB  - The synthesis of lipophosphoramidyl-beta-CD was obtained by an Atherton-Todd (AT)
      reaction that involved dioleylphosphite and either functionalized permethylated
      or native beta-cyclodextrin. This AT reaction that produced dioleylphosphoramide
      by making use of the amino group grafted on cyclodextrin, was optimized for these
      cyclic oligosaccharides. These new amphiphilic compounds were fully
      characterized, and their self-assembling properties were investigated: the mean
      size diameter and polydispersity measured by Dynamic Light Scattering (DLS) were
      affected by the nature of the aqueous media and the temperature of storage. The
      encapsulation properties of these nanoparticles have been evaluated using
      carboxyfluorescein and scopolamine derivatives as model of guests.

PMID- 21951980
TI  - Treating young individuals at clinical high risk for psychosis.
AB  - BACKGROUND: Typically, studies investigating those at clinical high risk for
      psychosis have focused on predictors of conversion and treatments that might
      prevent conversion to full-blown psychosis. Few studies have followed those who
      do not go on to develop a psychotic illness. METHODS: Participants were 48 young
      people who were at risk for developing psychosis based on the Structured
      Interview for Prodromal Symptoms criteria and participated in a treatment
      programme where they were offered up to 6 months of psychosocial treatment and
      psychiatric management. Attenuated psychotic symptoms, negative symptoms,
      depression, anxiety, social functioning, alcohol and drug use, and meta-cognitive
      beliefs were assessed at baseline, 6, 12 and 18 months. Personality
      characteristics were assessed at baseline. Medication use was tracked and
      psychiatric visits were logged over the 18-month study period. RESULTS: On
      average, participants attended 12 sessions of psychosocial treatment and had one
      meeting with the psychiatrist every 6 months. Only 24% were ever prescribed any
      psychotropic medications, and antipsychotics were not used. Significant
      improvements were found over time in attenuated positive symptoms, negative
      symptoms, depression, anxiety, meta-cognitions and social functioning with most
      improvement occurring in the first 6 months. There was no change in the level of
      substance use. For personality assessment, participants generally scored high on
      neuroticism and openness and had low scores on extraversion, agreeableness and
      conscientiousness. CONCLUSION: With minimal treatment and no antipsychotics,
      young people who present as being at risk for developing a psychotic disorder
      demonstrate clinical improvement over time. However, a few continued to have the
      liability of ongoing attenuated psychotic symptoms.

PMID- 21951981
TI  - IL28B polymorphism is associated with treatment response in patients with
      genotype 4 chronic hepatitis C.
AB  - BACKGROUND & AIMS: Polymorphisms in the region of the interleukin (IL)28B gene
      have been associated with pegylated-interferon (PEG-IFN) and ribavirin treatment
      response mainly in genotype 1 HCV infections. However, there are few data on HCV
      genotype 4 (HCV-4) infection. We evaluated, in a unique well-characterized cohort
      of HCV-4 patients, the association of IL28B polymorphism with response to
      treatment or liver disease severity. METHODS: This study included 164 HCV-4
      patients from different ethnic groups (Egyptian, European, and Sub-Saharan
      African). Among these patients, 82 were studied for response and 160 for disease
      severity. Free DNA extracted from all the 164 patient's serum samples was
      analyzed by direct sequencing of the SNP rs12979860 of IL28B. Genetic and bio
      clinical features from patients having sustained virological response (43 SVR
      patients) and from those who did not respond to treatment or had a relapse after
      the end of the treatment (39 NR patients) were compared. IL28B polymorphism was
      compared between the 78 patients with mild fibrosis (Metavir score F0-F1) and the
      82 with advanced fibrosis (F2-F4). RESULTS: Our data showed a better treatment
      response rate of the C allele of the IL28B gene SNP rs12979860 (p=0.0008). The
      response rates were 81.8%, 46.5%, and 29.4% for genotype CC, CT, and TT,
      respectively. No significant relationship was found between rs12979860 and the
      severity of the disease. CONCLUSIONS: The SNP rs12979860 is strongly associated
      with SVR in patients infected with HCV-4, but not with liver disease severity.
      Analysis of IL28B genotype might be used to guide treatment for these patients.

PMID- 21951984
TI  - Vilazodone: clinical basis for the US Food and Drug Administration's approval of
      a new antidepressant.
AB  - OBJECTIVE: Vilazodone was recently approved by the US Food and Drug
      Administration (FDA) for the treatment of major depressive disorder (MDD). The
      purpose of this review is to summarize the FDA's approach to its review of the
      clinical pharmacology and the clinical efficacy and safety data for this new drug
      application, important issues in its decision-making, and its conclusions. DATA
      SOURCES: The data sources for this review were the original raw data sets for all
      clinical trials included in the development program for vilazodone, as well as
      the sponsor's original analyses of these data. STUDY SELECTION: Data were
      available from 24 human trials involving vilazodone, and included a total of
      2,898 human subjects exposed to 1 or more doses of this drug. DATA EXTRACTION:
      The FDA had access to original raw data sets for these trials. RESULTS:
      Vilazodone is effective in treating MDD at a dose of 40 mg/d, but it needs to be
      incrementally adjusted to this dose to minimize gastrointestinal symptoms. It
      needs to be taken with food to ensure adequate plasma concentrations.
      Vilazodone's profile of adverse events is similar to that seen with selective
      serotonin reuptake inhibitors. No dose adjustment is needed based on age, gender,
      or renal or hepatic impairment. It is recommended that the vilazodone dose be
      reduced to 20 mg when it is taken with strong cytochrome P450 (CYP) 3A4
      inhibitors, eg, ketoconazole. Vilazodone is not expected to have important
      effects on the clearance of other drugs that are cytochrome P450 substrates.
      CONCLUSIONS: Vilazodone is a new treatment for MDD, but it is unknown whether it
      has any advantages compared to other drugs in the antidepressant class.

PMID- 21951982
TI  - Is the use of cholesterol in mortality risk algorithms in clinical guidelines
      valid? Ten years prospective data from the Norwegian HUNT 2 study.
AB  - RATIONALE, AIMS AND OBJECTIVES: Many clinical guidelines for cardiovascular
      disease (CVD) prevention contain risk estimation charts/calculators. These have
      shown a tendency to overestimate risk, which indicates that there might be
      theoretical flaws in the algorithms. Total cholesterol is a frequently used
      variable in the risk estimates. Some studies indicate that the predictive
      properties of cholesterol might not be as straightforward as widely assumed. Our
      aim was to document the strength and validity of total cholesterol as a risk
      factor for mortality in a well-defined, general Norwegian population without
      known CVD at baseline. METHODS: We assessed the association of total serum
      cholesterol with total mortality, as well as mortality from CVD and ischaemic
      heart disease (IHD), using Cox proportional hazard models. The study population
      comprises 52 087 Norwegians, aged 20-74, who participated in the Nord-Trondelag
      Health Study (HUNT 2, 1995-1997) and were followed-up on cause-specific mortality
      for 10 years (510 297 person-years in total). RESULTS: Among women, cholesterol
      had an inverse association with all-cause mortality [hazard ratio (HR): 0.94; 95%
      confidence interval (CI): 0.89-0.99 per 1.0 mmol L(-1) increase] as well as CVD
      mortality (HR: 0.97; 95% CI: 0.88-1.07). The association with IHD mortality (HR:
      1.07; 95% CI: 0.92-1.24) was not linear but seemed to follow a 'U-shaped' curve,
      with the highest mortality <5.0 and >=7.0 mmol L(-1) . Among men, the association
      of cholesterol with mortality from CVD (HR: 1.06; 95% CI: 0.98-1.15) and in total
      (HR: 0.98; 95% CI: 0.93-1.03) followed a 'U-shaped' pattern. CONCLUSION: Our
      study provides an updated epidemiological indication of possible errors in the
      CVD risk algorithms of many clinical guidelines. If our findings are
      generalizable, clinical and public health recommendations regarding the 'dangers'
      of cholesterol should be revised. This is especially true for women, for whom
      moderately elevated cholesterol (by current standards) may prove to be not only
      harmless but even beneficial.

PMID- 21951985
TI  - Alzheimer's disease: implications of the updated diagnostic and research
      criteria.

PMID- 21951986
TI  - Focus on childhood and adolescent mental health. A potpourri of timely topics.

PMID- 21951987
TI  - Adjunctive use of repetitive transcranial magnetic stimulation in depressed
      adolescents: a prospective, open pilot study.
AB  - OBJECTIVE: Depression is often a serious and debilitating illness in adolescents.
      Unfortunately, a significant number of adolescents do not respond to
      antidepressant medications or psychotherapy. Repetitive transcranial magnetic
      stimulation (rTMS) is a novel treatment intervention shown to benefit depression
      in adults. This study considered rTMS as an adjunctive treatment in adolescents
      with major depressive disorder. METHOD: This prospective, open, multicenter trial
      of active adjunctive rTMS was conducted with 8 adolescents with DSM-IV-TR major
      depressive disorder (MDD) that had not responded sufficiently to 2 adequate
      antidepressant medication trials. All subjects were maintained on a stable dose
      of a selective serotonin reuptake inhibitor during the trial. Thirty daily rTMS
      treatments were given 5 days per week over 6 to 8 weeks. rTMS was applied to the
      left dorsolateral prefrontal cortex (120% of motor threshold; 10 Hz; 4-second
      trains; 26-second intertrain interval; 75 trains) for a total of 3,000
      stimulations per treatment session. RESULTS: Seven of 8 adolescents completed all
      30 treatments. rTMS was well tolerated, and no significant safety issues were
      identified. Suicidal ideation was present at baseline in 3 of the adolescents,
      and it improved during treatment. The primary outcome measure was the Children's
      Depression Rating Scale-Revised (CDRS-R); results improved significantly from
      baseline (mean [SD]) (65.9 [6.6]) to treatment 10 (50.9 [12]), P < .02. The CDRS
      R scores continued to improve through the rTMS treatment series at treatment 20
      (40.1 [14]), P < .01; treatment 30 (32.6 [7.3]), P < .0001; and at 6-month follow
      up (32.7 [3.8]), P < .0001. CONCLUSIONS: This prospective open trial suggests
      that rTMS is a safe, feasible, and potentially effective adjunctive therapy for
      treatment-resistant MDD in adolescents. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00587639.

PMID- 21951988
TI  - Failure rate and "professional subjects" in clinical trials of major depressive
      disorder.

PMID- 21951990
TI  - Improving treatment adherence in patients with schizophrenia.
AB  - Nonadherence to antipsychotic medications is an enormous challenge for clinicians
      and patients in the treatment of schizophrenia. Nonadherence and partial
      adherence are associated with high rates of relapse, rehospitalization, and
      suicide attempts. Assessing adherence can be difficult because patients are
      likely to overestimate their medication adherence and may not report skipping
      doses or discontinuing medication. Strategies for assessing and improving
      adherence rates among patients with schizophrenia, including the use of long
      acting depot antipsychotic medications, are discussed.

PMID- 21951991
TI  - Performance improvement CME: algorithms and EMRs in depression.
AB  - Major depressive disorder is difficult to treat due to its chronic and recurrent
      nature and the poor performance of most pharmacologic treatment options. To
      improve patient outcomes, clinicians should become familiar with moderators of
      antidepressant response, implement measurement-based care, and follow treatment
      algorithms. The use of electronic medical records and computerized decision
      support systems may improve documentation and facilitate clinicians' adherence to
      current standards of care. This Performance Improvement activity focuses on
      improving treatment outcomes for antidepressant therapy through familiarity with
      moderators of antidepressant response and the use of treatment algorithms,
      measurement-based care, and electronic medical records.

PMID- 21951992
TI  - Prevalence and impact of ADHD in college students.
AB  - The prevalence of ADHD on college campuses has increased dramatically during the
      last several decades. The brain abnormalities caused by ADHD result in
      impairments in executive function, which in turn make ordinary college
      challenges, such as managing long-term class assignments and prioritizing
      academic and social life, especially difficult for those with ADHD. However,
      college students with ADHD who receive proper treatment and take advantage of on
      campus and community disability services can have a successful college career.

PMID- 21951994
TI  - Origin of the magnetic field induced changes of the transverse plasma mode in the
      c-axis infrared response of underdoped YBa2Cu3O(7-delta).
AB  - We report on results of our theoretical study of magnetic field induced changes
      of the c-axis infrared response of bilayer cuprate superconductors using the
      phenomenological multilayer model involving the conductivity of the spacing
      layers and that of the bilayer units. For H perpendicular to the planes, the
      local conductivities have been expressed in terms of a two-fluid approximation-
      as weighted averages of the superconducting state ones and the normal state ones
      representing contributions of the vortex cores, the weight of the latter
      increasing linearly with the field. This allows us to reproduce and interpret the
      fast decrease with increasing H of the well known 400 cm(-1) peak (transverse
      plasma mode) in the c-axis conductivity, observed by LaForge and co-workers. For
      the local conductivities of underdoped YBa(2)Cu(3)O(7-delta) with T(c)=58 K
      reported by Dubroka and co-workers and the fraction of the normal state (T ~
      T(c)) component given by (MU(0)H/25 T), the computed field induced changes of the
      reflectivity are in quantitative agreement with the data. This suggests that the
      response at H=0 and T ~ T(c) is close to that at H=25 T < H(c2) and T ? T(c), in
      accord with theories attributing the above T(c) state to that of a superconductor
      lacking long-range phase coherence. Also discussed are changes of the response
      induced by H parallel to the CuO(2) planes.

PMID- 21951993
TI  - Inhaled surfactant in the treatment of accidental talc powder inhalation: a new
      case report.
AB  - The use of talcum powder is incorrectly part of the traditional care of infants.
      Its acute aspiration is a very dangerous condition in childhood. Although the use
      of baby powder has been discouraged from many authors and the reports of its
      accidental inhalation have been ever more rare, sometimes new cases with several
      fatalities have been reported. We report on a patient in which accidental
      inhalation of baby powder induced severe respiratory difficulties. We also point
      out the benefits of surfactant administration. Surfactant contributed to the
      rapid improvement of the medical and radiological condition, preventing severe
      early and late complications and avoiding invasive approaches.

PMID- 21951995
TI  - The role and influence of grandmothers on child nutrition: culturally designated
      advisors and caregivers.
AB  - Improving the nutritional status of infants and young children in developing
      countries depends to a significant extent on adoption of optimal nutrition
      related practices within the context of the household. Most policies, research
      and programmes on child nutrition in non-Western societies focus narrowly on the
      mother-child dyad and fail to consider the wider household and community
      environments in which other actors, hierarchical patterns of authority and
      informal communication networks operate and influence such practices. In
      particular, the role and influence of senior women, or grandmothers, has received
      limited attention. Research dealing with child nutrition from numerous socio
      cultural settings in Africa, Asia and Latin America reveals three common patterns
      related to the social dynamics and decision-making within households and
      communities. First, grandmothers play a central role as advisers to younger women
      and as caregivers of both women and children on nutrition and health issues.
      Second, grandmother social networks exercise collective influence on maternal and
      child nutrition-related practices, specifically regarding pregnancy, feeding and
      care of infants, young children and sick children. Third, men play a relatively
      limited role in day-to-day child nutrition within family systems. The research
      reviewed supports the need to re-conceptualize the parameters considered in
      nutritional policies and programmes by expanding the focus beyond the mother
      child dyad to include grandmothers given their role as culturally designated
      advisers and caregivers.

PMID- 21951996
TI  - Evaluation of the Clearview(r) Malaria pLDH Malaria Rapid Diagnostic Test in a
      non-endemic setting.
AB  - BACKGROUND: Malaria Rapid Diagnostic Tests (RDTs) are widely used to diagnose
      malaria. The present study evaluated a new RDT, the Clearview(r) Malaria pLDH
      test targeting the pan-Plasmodium antigen lactate dehydrogenase (pLDH). METHODS:
      The Clearview(r) Malaria pLDH test was evaluated on fresh samples obtained in
      returned international travellers using microscopy corrected by PCR as the
      reference method. Included samples were Plasmodium falciparum (139), Plasmodium
      vivax (22), Plasmodium ovale (20), Plasmodium malariae (7), and 102 negative.
      RESULTS: Overall sensitivity for the detection of Plasmodium spp was 93.2%. For
      P. falciparum, the sensitivity was 98.6%; for P. vivax, P. ovale and P. malariae,
      overall sensitivities were 90.9%, 60.0% and 85.7% respectively. For P. falciparum
      and for P. vivax, the sensitivities increased to 100% at parasite densities above
      100/MUl. The specificity was 100%. The test was easily to perform and the result
      was stable for at least 1 hour. CONCLUSION: The Clearview(r) Malaria pLDH was
      efficient for the diagnosis of malaria. The test was very sensitive for P.
      falciparum and P. vivax detection. The sensitivities for P. ovale and P. malariae
      were better than other RDTs.

PMID- 21951997
TI  - Incidence of pregnancy-associated venous thromboembolism in Korea: from the
      Health Insurance Review and Assessment Service database.

PMID- 21951998
TI  - The oral iron chelator deferasirox induces apoptosis in myeloid leukemia cells by
      targeting caspase.

PMID- 21951999
TI  - PHD1 interacts with ATF4 and negatively regulates its transcriptional activity
      without prolyl hydroxylation.
AB  - Cellular response to hypoxia plays an important role in both circulatory and
      pulmonary diseases and cancer. Hypoxia-inducible factors (HIFs) are major
      transcription factors regulating the response to hypoxia. The alpha-subunits of
      HIFs are hydroxylated by members of the prolyl-4-hydroxylase domain (PHD) family,
      PHD1, PHD2, and PHD3, in an oxygen-dependent manner. Here, we report on the
      identification of ATF4 as a protein interacting with PHD1 as well as PHD3, but
      not with PHD2. The central region of ATF4 including the Zipper II domain, ODD
      domain and beta-TrCP recognition motif were involved in the interaction with
      PHD1. Coexistence of PHD1 stabilized ATF4, as opposed to the destabilization of
      ATF4 by PHD3. Moreover, coexpression of ATF4 destabilized PHD3, whereas PHD1
      stability was not affected by the presence of ATF4. Mutations to alanine of
      proline residues in ATF4 that satisfied hydroxylation consensus by PHDs did not
      affect binding activity of ATF4 to PHD1 and PHD3. Furthermore, in vitro prolyl
      hydroxylation assay clearly indicated that ATF4 did not serve as a substrate of
      both PHD1 and PHD3. Coexpression of PHD1 or PHD3 with ATF4 repressed the
      transcriptional activity of ATF4. These results suggest that PHD1 and PHD3
      control the transactivation activity of ATF4.

PMID- 21952001
TI  - First-trimester screening for trisomy 21 using alpha-fetoprotein.
AB  - OBJECTIVE: To investigate the potential value of adding maternal serum alpha
      fetoprotein (AFP) to free beta-human chorionic gonadotropin (beta-hCG) and PAPP-A
      and fetal nuchal translucency (NT) thickness in first-trimester screening for
      trisomy 21. METHODS: In this case control study, serum AFP was measured in 100
      trisomy 21 and 1,500 euploid pregnancies in which screening for trisomy 21 had
      been performed by a combination of serum free beta-hCG and PAPP-A and fetal NT at
      11-13 weeks' gestation. We examined the effect of adding AFP on the performance
      of screening by the combined test. RESULTS: In the trisomy 21 pregnancies, the
      median multiple of the normal median AFP, adjusted for gestational age, maternal
      weight, racial origin, smoking status and method of conception, was significantly
      reduced (0.7037, 95% CI: 0.6398-0.7739). Adding AFP to the combined test improved
      the performance of screening and for a risk cut-off of 1 in 100, the false
      positive rate was reduced from 2.8 by 0.4% (95% CI: 0.13-0.77%) without a
      significant change in detection rate. CONCLUSIONS: Inclusion of serum AFP
      improves the performance of the first-trimester combined test in screening for
      trisomy 21.

PMID- 21952000
TI  - Involvement of peripheral ionotropic glutamate receptors in orofacial thermal
      hyperalgesia in rats.
AB  - BACKGROUND: The purpose of the present study was to elucidate the mechanisms that
      may underlie the sensitization of trigeminal spinal subnucleus caudalis (Vc) and
      upper cervical spinal cord (C1-C2) neurons to heat or cold stimulation of the
      orofacial region following glutamate (Glu) injection. RESULTS: Glu application to
      the tongue or whisker pad skin caused an enhancement of head-withdrawal reflex
      and extracellular signal-regulated kinase (ERK) phosphorylation in Vc-C2 neurons.
      Head-withdrawal reflex and ERK phosphorylation were also enhanced following cold
      stimulation of the tongue but not whisker pad skin in Glu-injected rats, and the
      head-withdrawal reflex and ERK phosphorylation were enhanced following heat
      stimulation of the tongue or whisker pad skin. The enhanced head-withdrawal
      reflex and ERK phosphorylation after heat stimulation of the tongue or whisker
      pad skin, and those following cold stimulation of the tongue but not whisker pad
      skin were suppressed following ionotropic glutamate receptor antagonists
      administration into the tongue or whisker pad skin. Furthermore, intrathecal
      administration of MEK1/2 inhibitor PD98059 caused significant suppression of
      enhanced head-withdrawal reflex in Glu-injected rats, heat head-withdrawal reflex
      in the rats with Glu injection into the tongue or whisker pad skin and cold head
      withdrawal reflex in the rats with Glu injection into the tongue. CONCLUSIONS:
      The present findings suggest that peripheral Glu receptor mechanisms may
      contribute to cold hyperalgesia in the tongue but not in the facial skin, and
      also contribute to heat hyperalgesia in the tongue and facial skin, and that the
      mitogen-activated protein kinase cascade in Vc-C2 neurons may be involved in
      these Glu-evoked hyperalgesic effects.

PMID- 21952002
TI  - Influence of moderate, daily physical activity on body composition and blood
      lipid profile in Swedish adults.
AB  - BACKGROUND: Health organizations suggest that adults ought to engage in at least
      30 minutes of moderate-intensity daily physical activity. This study investigated
      the effects of a 30-minute single daily bout of brisk walking upon risk factors
      for coronary heart disease with blood lipid profile in particular. METHODS:
      Thirty-three (25-45 y) adults, were randomly assigned into an exercise group (EG;
      n=16, 9w) and a control group (CG; n=17, 6w). The EG walked briskly 30 minutes
      daily during the 3-week test period. Compliance/adherence was maximal throughout
      the 3-week intervention due to stringent daily monitoring. RESULTS: The EG showed
      a significant decrease in concentrations of low density lipoprotein cholesterol
      (LDL-C) and total cholesterol (TC) during the intervention period. A significant
      inverse correlation between Delta energy expenditure/day and DeltaLDL-C (r=-0.39,
      P<.05) and an improvement in weight and BMI in the EG was found. Average steps
      during 30 minutes brisk walking bout was 3669 steps/bout generating a mean energy
      expenditure of 191 kcal/ bout. CONCLUSIONS: The most unique findings were that
      daily single bouts of moderate-intensity physical activity for 30 minutes, during
      3 weeks, induced favorable effects upon body weight, BMI, and blood concentration
      of LDL-C and TC in healthy adults.

PMID- 21952003
TI  - Time to treatment initiation with oral antihyperglycaemic therapy in US patients
      with newly diagnosed type 2 diabetes.
AB  - AIM: To compare the time from initial diagnosis to initiation with oral
      antihyperglycaemic treatment in younger versus older patients with type 2
      diabetes, and to evaluate factors associated with initiating treatment. METHODS:
      This was a retrospective US cohort study with a 2-year follow-up period after
      diagnosis of type 2 diabetes. Using the General Electric Healthcare's Clinical
      Data Services electronic medical record database, eligible patients included
      those aged >=30 years at initial diagnosis of type 2 diabetes between January
      2003 and December 2005. In the 2-year period following diagnosis, the time to the
      first prescription of an oral antihyperglycaemic agent was compared between
      younger (30-64 years) and older (>=65 years) patients. Factors associated with
      time to treatment with an oral antihyperglycaemic agent were examined using Cox
      proportional hazards regression. RESULTS: Of the 10 743 patients with newly
      diagnosed type 2 diabetes, 43% were >=65 years old. The mean age at diagnosis was
      73 years for older patients and 52 years for younger patients. Compared to
      younger patients, a greater proportion of older patients had a baseline
      haemoglobin A1c (HbA1c) value <7% (38 vs. 32%; p < 0.001). In the 2-year follow
      up period, a significantly greater proportion of younger patients (59%) received
      oral antihyperglycaemic treatment compared to older patients (44%; p < 0.001).
      The median time between diagnosis and initiating treatment with an oral
      antihyperglycaemic agent was 350 days for younger patients and >2 years for older
      patients. After adjusting for covariates, older patients had a greater risk of
      not receiving treatment with oral antihyperglycaemic therapy than younger
      patients [adjusted hazard ratio = 0.82 (95% confidence interval: 0.75, 0.90)].
      CONCLUSIONS: In patients with newly diagnosed type 2 diabetes, the time to
      initiation of oral antihyperglycaemic therapy was significantly longer in older
      patients (>=65 years old) than younger patients (<65 years).

PMID- 21952004
TI  - Early repolarization patterns: the good, the bad, and the ugly?

PMID- 21952005
TI  - Computed tomography's crucial role in averting a life-threatening complication of
      lead extraction.

PMID- 21952006
TI  - Arrhythmia formation in subclinical ("silent") long QT syndrome requires multiple
      insults: quantitative mechanistic study using the KCNQ1 mutation Q357R as
      example.
AB  - BACKGROUND: In subclinical or silent long QT syndrome, the QT interval is normal
      under basal conditions. The hypothesis that insults to the repolarization reserve
      may cause arrhythmias in silent mutation carriers but not in noncarriers has been
      proposed as a general principle, yet crucial aspects remain descriptive, lacking
      quantification. OBJECTIVE: To utilize accurate mathematical models of the human
      action potential and beta-adrenergic stimulation to quantitatively investigate
      arrhythmia-formation mechanisms peculiar to silent long QT syndrome, using
      mutation Q357R in KCNQ1 (alpha subunit of slow-delayed rectifier I(Ks)) as a
      paradigm. METHODS: Markov models were formulated to account for altered I(Ks)
      kinetics in Q357R compared with wild type and introduced into a detailed model of
      the human ventricular myocyte action potential. RESULTS: Dominant negative loss
      of I(Ks) available reserve accurately represents Q357R. Action potential
      prolongation with mutant I(Ks) was minimal, reproducing the silent phenotype.
      Partial block of rapid delayed rectifier current (I(Kr)) was needed in addition
      to fast pacing and isoproterenol application to cause early afterdepolarizations
      (EADs) in epicardial cells with mutant I(Ks), but this did not produce EADs in
      wild type. Reduced channel expression at the membrane, not I(Ks) kinetic
      differences, caused EADs in the silent mutant. With mutant I(Ks), isoproterenol
      plus partial I(Kr) block resulted in dramatic QT prolongation in the pseudo
      electrocardiogram and EADs formed without I(Kr) block in mid-myocardial cells
      during simulated exercise onset. CONCLUSION: Multiple severe insults are needed
      to evince an arrhythmic phenotype in silent mutation Q357R. Reduced membrane
      I(Ks) expression, not kinetic changes, underlies the arrhythmic phenotype.

PMID- 21952007
TI  - Feasibility of postmortem device acquisition for potential reuse in underserved
      nations.
AB  - OBJECTIVES: The purpose of the present study was to examine the feasibility and
      efficacy of a program to acquire devices with adequate battery life from
      crematories and funeral homes for potential reutilization in underserved nations.
      BACKGROUND: There exists a great health-care disparity between the industrialized
      world and underserved nations--specifically in the frequency of pacemaker
      implantation. METHODS: Flyers were mailed to all 1057 members of the Michigan
      Funeral Directors Association providing information to download a consent-for
      explant form and request a postage-paid envelope from www.myheartyourheart.org in
      order to send explanted devices. Donated devices from funeral homes and
      crematories nationwide were also collected from World Medical Relief. Adequate
      battery life was defined as >=75% or >=4 years of estimated longevity. RESULTS: A
      total of 3176 devices (65% pacemakers, 21% implantable cardioverter
      defibrillators [ICDs], 12% biventricular ICDs, and 3% biventricular pacemakers)
      were donated to the reutilization program. Five hundred fifty devices (21%; 95%
      confidence interval [CI] 19.4-22.6%) were found to have an acceptable battery
      life for reutilization. Among these devices, 313 were pacemakers (17.9%; 95% CI
      16.1-19.8%), 118 were ICDs (17.9%; 95% CI 15.1-21.1%), 112 were biventricular
      ICDs (30.3%; 95% CI 25.6-35.2%), and 7 were biventricular pacemakers (17.3%; 95%
      CI 16.0-18.7%). CONCLUSIONS: Approximately 21% of donated devices and 30% of
      donated biventricular ICDs possess an adequate battery life for potential reuse.
      Device donations from funeral homes and crematories appear to be a potential
      resource for device reutilization for those in need in underserved nations.

PMID- 21952008
TI  - Pharyngocutaneous fistula complicating laryngectomy: can metronidazole help?
AB  - AIM: To evaluate the use of metronidazole as a prophylactic agent against
      pharyngocutaneous fistula (PCF) formation. PATIENTS AND METHODS: Seventy patients
      who underwent total laryngectomy between 2000 and 2008 in our department were
      divided into two groups. The first group (M+ group) was placed on a 10-day
      metronidazole regimen (2 days prior to surgery and 7 days following). The second
      group (M- group) received only regular preoperative chemoprophylaxis. RESULTS: In
      total, 17 (24.3%) incidents of PCF were reported, 3 of which were in the M+
      group, with the remainder in the M- group. A statistically significant reduction
      in the PCF rate was noted in favor of metronidazole in the overall population (p
      = 0.005), as well as in the patient group that had received radiotherapy prior to
      surgery (p = 0.03). CONCLUSION: Metronidazole administered for a total of 10 days
      pre- and postoperatively seems to lower the incidence rate of PCF formation.

PMID- 21952009
TI  - Defining and describing the pre-dementia stages of familial Alzheimer's disease.
AB  - With the prospect of prevention trials for familial Alzheimer's disease on the
      horizon, understanding the natural history of the illness has never been so
      important. Earlier this year in The Lancet Neurology, Acosta-Baena and colleagues
      published the results of the largest and longest retrospective study of pre
      dementia clinical stages in familial Alzheimer's disease to date. By reviewing
      serial neuropsychological assessments of individuals from a large Colombian
      kindred affected by the E280A mutation in the Presenilin 1 gene, they defined
      three stages of pre-dementia cognitive impairment. Using survival analyses, the
      authors estimated the median age at onset and rate of progression through each of
      these stages towards dementia and ultimately death. Their study provides valuable
      insights into the time course of cognitive decline associated with this mutation.
      Furthermore, the study highlights some of the challenges of defining pre-dementia
      clinical stages in familial Alzheimer's disease and the need for the field to
      develop a consistent terminology.

PMID- 21952011
TI  - Safety culture a must.

PMID- 21952010
TI  - Efficacy and safety of recombinant tissue plasminogen activator and gas versus
      bevacizumab and gas for subretinal haemorrhage.
AB  - PURPOSE: To report the 12 months efficacy of initial intravitreal bevacizumab or
      intravitreal recombinant tissue plasminogen activator (rtPA) combined with
      expansile gas in patients with subretinal haemorrhage caused by neovascular age
      related macular degeneration (AMD). METHODS: Forty-five eyes of 45 patients with
      subretinal haemorrhage (1-5 disc diameters) involving the fovea secondary to
      neovascular AMD were evaluated retrospectively consecutively. Thirty-two eyes
      underwent treatment with rtPA (50 MUg/0.05 ml) combined with intravitreal sulphur
      hexafluoride (SF6). The other 13 eyes were treated with bevacizumab (1.25 mg/0.05
      ml) and SF6. Thereafter, all patients received Vascular Endothelial Growth Factor
      (anti-VEGF) treatment according to modified PrONTO criteria. Main outcome was
      change of best-corrected visual acuity (VA) at 12 months as determined by Early
      Treatment Diabetic Retinopathy (ETDRS). RESULTS: There was more improvement in
      patients initially treated with rtPA and gas (14 letters; bevacizumab and gas
      eight letters) and not suffering from adverse events. The incidence of vitreous
      haemorrhages was significantly higher in the rtPA group (nine of 32 versus one of
      13, p < 0.01). In both groups, an average of 3.5 anti-VEGF injections were
      performed per patient during 12 months (no difference between both groups).
      CONCLUSION: Both initial treatment regimen lead to improved functional results
      after 1 year. However, patients, not suffering from adverse events, who underwent
      initial treatment with rtPA and gas showed better results. To maintain VA,
      controlling neovascular AMD by anti-VEGF treatment regime after initial treatment
      with rtPA+gas is important for all cases.

PMID- 21952012
TI  - Wherefore art though, ACOs?

PMID- 21952013
TI  - Connect and engage for better nurse retention.

PMID- 21952014
TI  - 10 ways to practice evidence-based staffing and scheduling.

PMID- 21952015
TI  - The "dance of caring persons".

PMID- 21952017
TI  - Avoiding "groupthink": a manager's challenge.

PMID- 21952018
TI  - Stressed out! Strategies for enhancing performance.

PMID- 21952019
TI  - Structuring education; investing in staffing.

PMID- 21952020
TI  - Understanding the experiences and service needs of siblings of individuals with
      first-episode psychosis: a phenomenological study.
AB  - BACKGROUND: Despite recent focus on developing family-inclusive services to meet
      the needs of young people with first-episode psychosis, the needs of their
      siblings are often overlooked. AIMS: This study explored the experiences and
      needs of siblings of young adults with first-episode psychosis receiving support
      from two Early Intervention in Psychosis Services in South-East England. METHODS:
      Thirty-one siblings aged 11-35 years, were given a semi-structured interview to
      gather their perspectives and accounts of their lived experiences. The resultant
      rich qualitative data was analysed using responsive-reader and framework methods.
      RESULTS: Six themes were identified: siblings' roles and involvement; emotions;
      impact on relationships; coping patterns; resilience; and siblings' service
      needs. CONCLUSION: All participants had been greatly affected by the onset of the
      psychosis in their brother or sister. Most siblings did not identify themselves
      as carers, although most played a significant part in their brother's or sister's
      life. Participants wanted dynamic, robust and accessible services, especially
      information and peer support to meet their needs.

PMID- 21952021
TI  - Healthcare issue.

PMID- 21952022
TI  - Responsibility for Canada's healthcare quality agenda: interviews with Canadian
      health leaders.
AB  - Canadian healthcare is under increased scrutiny to improve quality and
      performance, and for good reason. The proliferation of provincial-level quality
      councils underscores the urgency to establish an aligned national quality agenda.
      Patient safety has long been held as a critical element of a high-quality
      healthcare system; with the inexorable growth in spending, efficiency has more
      recently been introduced. Efficiency and quality are both factors in Ontario's
      Excellent Care for All legislation introduced in June of 2010, and Quebec's
      l'Institut national d'excellence en sante et en services sociaux (INESSS) arising
      from the Castonguay report. These associations of quality and efficiency are also
      echoed in the US, Australian and UK public debates. The development of a quality
      agenda has concurrently precipitated discussion regarding responsibility for
      quality, particularly but not exclusively with the emergence of quality issues in
      the technical and interpretive pathology arena. The discussion and debate on
      responsibility have become preoccupations at the national, provincial,
      institutional and individual profession levels.

PMID- 21952023
TI  - The healthcare quality agenda in Canada.
AB  - Sullivan et al. have captured several important themes. One of the reasons that
      healthcare has been slow to adopt a culture of quality has been that it has taken
      a long time to recognize that quality is a continuous journey along several
      dimensions. Following advances in the early 1990s on appropriateness and
      effectiveness, there has been a decade-long preoccupation with accessibility that
      still remains an issue. Patient-centredness is one of the most recent dimensions
      to receive attention, and the overall goal of quality - improved patient outcomes
      - needs considerable work. Measurement and reporting are fundamental to quality
      improvement, but the provincial and territorial governments have not lived up to
      their Health Accord commitments to regular reporting on common indicators. At
      least six provinces have established health quality councils, but it remains to
      be seen if this bottom-up approach will lead to a common reporting framework that
      will support benchmarking. Canada would likely benefit from a pan-Canadian
      approach to innovation in healthcare quality.

PMID- 21952024
TI  - What's on the quality agenda? Acknowledging progress, respecting the challenges.
AB  - While many quality improvement and performance measurement initiatives are under
      way in Canada and beyond, there are challenges to be met around effectively
      coordinating the national quality agenda, sharing expertise and reducing
      duplication. An important first step has been recognizing the vital connection
      between quality and efficiency.While many provinces and territories have embraced
      the quality challenge, the national quality agenda remains less than coordinated.
      Reaching agreement on goals must be done in full collaboration with the provinces
      and territories, respecting their unique priorities while also providing the
      benefits of a national measurement and performance system and broader-level
      strategies.Workplace culture affects the ability to deliver safe care. Creating
      an integrated culture of quality results in measurable improvements in staff
      satisfaction and patient outcomes. However, this process requires long-term
      commitments from governments, boards, chief executive officers (CEOs) and staff,
      and involvement at all levels in design, initiation and implementation.There is
      frustration with the extensive and growing number of bodies to whom health
      organizations must submit data. This duplication could be reduced through
      consistent definitions, measurement priorities and reporting mechanisms, as well
      as national agreement on core performance measures. Ongoing collaboration at many
      levels is increasing the sharing of information and aligning of definitions in
      this regard.

PMID- 21952025
TI  - You just need to get started.
AB  - An organization can drive quality only through its people. Too often, we relegate
      quality to a single department or a small group of evangelical leaders but fail
      to make it everyone's business. Accountability has become a buzzword, and we have
      translated it into huge agreements with myriads of measures and indicators, all
      purporting to have something to do with quality.Institutions need to focus on a
      few things to improve quality. How do you build a culture? You plan, you pick
      certain goals to which you aspire, you set targets and you measure against those
      targets. You provide the skills, knowledge, expertise and infrastructure
      necessary to enable people to meet those targets, and then you drive for them.
      And you are transparent about it.I often think that we overcomplicate quality. As
      I have said repeatedly, it is as simple as choosing a measure, planning to
      implement some changes and re-measuring to see if your changes have had any
      impact. You don't need a national council, or even a provincial one, to make
      quality happen in the day-to-day operations of every healthcare organization in
      the country. Rather, you just need to get started.

PMID- 21952026
TI  - Building a safety and quality culture in healthcare: where it starts.
AB  - Healthcare in Canada underachieves stakeholders' expectations for safe, high
      quality care. The authors maintain that a common understanding of, and vision
      for, what is required to achieve improved outcomes for patients is missing.
      Educating tomorrow's healthcare professionals is paramount to address this
      critical shortfall. However, healthcare educational institutions must themselves
      break out of a 20th-century paradigm of viewing healthcare safety and quality as
      functions of individual healthcare providers rather than as properties of the
      clinical micro- and meso-systems within which they function and are a part.
      Canadian healthcare systems are ailing; like treating a sick patient,
      interventions should be grounded on a solid understanding of anatomy (structure)
      and physiology (function). The Healthcare Encounter Safety and Quality Model
      (HESQM) highlights the structures underlying healthcare delivery and the key
      system functions required to achieve safe, high-quality care. The model has been
      used to frame the University of Calgary Faculty of Medicine's educational
      strategy for achieving safer, higher-quality care. The HESQM is based on
      leadership - leaders whose decisions and actions are guided by core safety and
      quality principles. Today's and especially tomorrow's healthcare leaders require
      a common understanding of how to achieve higher-performing healthcare systems; it
      is the responsibility of Canada's post-secondary institutions to deliver it.

PMID- 21952027
TI  - Responsibility for Canada's healthcare quality agenda: the home and community
      sector.
AB  - In their study on the current state of the quality agenda in the Canadian
      healthcare system, Sullivan and colleagues interviewed healthcare leaders across
      Canada who predominantly represent the hospital care sector. The home and
      community sector is under-represented in research and discussions about quality
      and patient safety, despite the fact that it is the fastest-growing sector in
      healthcare. Patient safety research in home care has been spearheaded by VON
      Canada and the Canadian Patient Safety Institute since 2005. Quality and safety
      are not just parallel imperatives; rather, they are inextricably linked concepts
      that rely on each other to function effectively. Safety for clients or patients
      is complex when multiple organizations, regulated and unregulated paid providers
      and unpaid family caregivers make up the team providing care in an uncontrolled
      home environment. Add to this the pressure of reducing costs while increasing
      home care admissions, and the equation seems impossible. Client or patient
      participation is increasingly recognized and advocated as a main component in the
      redesign of healthcare processes to improve patient safety and may provide a key
      organizing principle for better care and outcomes.

PMID- 21952028
TI  - The PROMise of quality improvement in healthcare: will Canada choose the right
      road?
AB  - Canadians pride themselves in their healthcare system. Yet, multiple problems are
      the focus of ongoing debates. The adoption of effective clinical and
      organizational interventions to improve health outcomes has not kept pace with
      the science. Solutions lie in health system redesign to improve quality and
      efficiency, focusing on the goal of improving population health. This commentary
      addresses the original conception behind medicare - an unfinished task; the
      implementation of a quality agenda; and the use of patient-reported outcome
      measures (PROMs) to inform the development and evaluation of tailored
      interventions. Finally, it offers considerations for moving the health system
      forward toward the ultimate goal of keeping people well.

PMID- 21952029
TI  - We have a perfect storm - let's use it.
AB  - The lead paper, "Responsibility for Canada's Healthcare Quality Agenda:
      Interviews with Canadian Health Leaders," is a valuable contribution to the
      quality and safety improvement conversations taking place across the country. My
      commentary suggests a dramatic convergence of social, economic, demographic and
      technological forces has brought healthcare to a threshold of a perfect storm. To
      brace ourselves against this storm, I have suggested that we need to understand
      the system not as a structure but as relationships. I argue that alignment is not
      a concept that is particularly well understood - and we tend to focus almost
      exclusively on the component of structure.

PMID- 21952030
TI  - National quality framework - yes we can!
AB  - This commentary provides perspectives from the nursing profession on the lead
      article that address professional and regulatory issues and shares insights
      derived from many years of leading quality enhancement initiatives at policy and
      clinical levels. The commentary calls attention to a number of successful
      national and provincial approaches founded on strong leadership, collaboration
      and consensus building. It also underscores the idea that professional
      organizations and individual health professionals are important drivers of
      quality initiatives at the point of care and when overseeing adherence to
      standards and successful program implementation.

PMID- 21952031
TI  - Healing healthcare in Canada: a shared agenda for healthcare quality and
      sustainability.
AB  - Sullivan et al. make a compelling argument that a "coalition of the willing" must
      seize the nettle and create a national agenda and the capacity for quality
      leadership in Canadian healthcare. While there is reason to believe that Canada
      could benefit from such an agenda, there is also evidence that, if done
      incorrectly, such an agenda could be expensive and counterproductive. To increase
      the likelihood that a national quality agenda will contribute to the creation of
      a sustainable and effective healthcare system, it will be important to understand
      potential pitfalls and to incorporate approaches that have enabled leading
      organizations to achieve success. It will be key to create a shared vision of
      healthcare that focuses on the health needs of our population and engages
      stakeholders broadly.

PMID- 21952033
TI  - Coexistence of exchange bias and magnetization pinning in the MnO(x)/GaMnAs
      system.
AB  - Coexistence of exchange bias (H(E)) and magnetization (M) shift was observed in
      as-grown and field-annealed MnO(x)/Ga(0.95)Mn(0.05)As bilayers. It was found that
      H(E) initially decreases with the annealing time t(a) and then increases when
      t(a) > 30 min, while the M shift remains almost unchanged with t(a). X-ray
      photoelectron spectroscopy (XPS) analysis reveals that MnO(x) is composed of MnO
      and Mn(3)O(4), and the volume amount ratio of Mn(3)O(4) to MnO increases with
      increasing t(a). A simple model based on a uniform MnO-Mn(3)O(4) interface with
      constant 'pinned' uncompensated interfacial spins is proposed to account for the
      observed exchange-biased phenomena in the bilayers.

PMID- 21952034
TI  - Comparison of two modes of vitamin B12 supplementation on neuroconduction and
      cognitive function among older people living in Santiago, Chile: a cluster
      randomized controlled trial. a study protocol [ISRCTN 02694183].
AB  - BACKGROUND: Older people have a high risk of vitamin B12 deficiency; this can
      lead to varying degrees of cognitive and neurological impairment. CBL deficiency
      may present as macrocytic anemia, subacute combined degeneration of the spinal
      cord, or as neuropathy, but is often asymptomatic in older people. Less is known
      about subclinical vitamin B12 deficiency and concurrent neuroconduction and
      cognitive impairment. A Programme of Complementary Feeding for the Older
      Population (PACAM) in Chile delivers 2 complementary fortified foods that provide
      approximately 1.4 MUg/day of vitamin B12 (2.4 MUg/day elderly RDA). The aim of
      the present study is to assess whether supplementation with vitamin B12 will
      improve neuroconduction and cognitive function in older people who have
      biochemical evidence of vitamin B12 insufficiency in the absence of clinical
      deficiency. METHODS: We designed a cluster double-blind placebo-controlled trial
      involving community dwelling people aged 70-79 living in Santiago, Chile. We
      randomized 15 clusters (health centers) involving 300 people (20 per cluster).
      Each cluster will be randomly assigned to one of three arms: a) a 1 mg vitamin
      B12 pill taken daily and a routine PACAM food; b) a placebo pill and the milk
      PACAM food fortified to provide 1 mg of vitamin B12; c) the routine PACAM food
      and a placebo pill.The study has been designed as an 18 month follow up period.
      The primary outcomes assessed at baseline, 4, 9 and 18 months will be: serum
      levels of vitamin B12, neuroconduction and cognitive function. CONCLUSIONS: In
      view of the high prevalence of vitamin B12 deficiency in later life, the present
      study has potential public health interest because since it will measure the
      impact of the existing program of complementary feeding as compared to two
      options that provide higher vitamin B12 intakes that might potentially may
      contribute in preserving neurophysiologic and cognitive function and thus improve
      quality of life for older people in Chile. TRIAL REGISTRATION: ISRCTN:
      ISRCTN02694183.

PMID- 21952035
TI  - Clenbuterol suppresses proteasomal and lysosomal proteolysis and atrophy-related
      genes in denervated rat soleus muscles independently of Akt.
AB  - Although it is well known that administration of the selective beta(2)-adrenergic
      agonist clenbuterol (CB) protects muscle following denervation (DEN), the
      underlying molecular mechanism remains unclear. We report that in vivo treatment
      with CB (3 mg/kg sc) for 3 days induces antiproteolytic effects in normal and
      denervated rat soleus muscle via distinct mechanisms. In normal soleus muscle, CB
      treatment stimulates protein synthesis, inhibits Ca(2+)-dependent proteolysis,
      and increases the levels of calpastatin protein. On the other hand, the
      administration of CB to DEN rats ameliorates the loss of muscle mass, enhances
      the rate of protein synthesis, attenuates hyperactivation of proteasomal and
      lysosomal proteolysis, and suppresses the transcription of the lysosomal protease
      cathepsin L and of atrogin-1/MAFbx and MuRF1, two ubiquitin (Ub) ligases involved
      in muscle atrophy. These effects were not associated with alterations in either
      IGF-I content or Akt phosphorylation levels. In isolated muscles, CB (10(-6) M)
      treatment significantly attenuated DEN-induced overall proteolysis and
      upregulation in the mRNA levels of the Ub ligases. Similar responses were
      observed in denervated muscles exposed to 6-BNZ-cAMP (500 MUM), a PKA activator.
      The in vitro addition of triciribine (10 MUM), a selective Akt inhibitor, did not
      block the inhibitory effects of CB on proteolysis and Ub ligase mRNA levels.
      These data indicate that short-term treatment with CB mitigates DEN-induced
      atrophy of the soleus muscle through the stimulation of protein synthesis,
      downregulation of cathepsin L and Ub ligases, and consequent inhibition of
      lysosomal and proteasomal activities and that these effects are independent of
      Akt and possibly mediated by the cAMP/PKA signaling pathway.

PMID- 21952037
TI  - Disruption of paraoxonase 3 impairs proliferation and antioxidant defenses in
      human A549 cells and causes embryonic lethality in mice.
AB  - We had shown previously that paraoxonase 3 (PON3), a putative circulating
      antioxidant, was systemically upregulated in late-gestation rat, sheep, and human
      fetuses. Our overarching hypothesis is that preterm human infants are delivered
      with low levels of PON3 and that this contributes to a state of oxidative stress.
      We sought to determine whether absence of Pon3 was associated with reduced
      neonatal viability in mice and studied the offspring from crosses between Pon3(+/
      ) mice. The number of Pon3(-/-) animals at E10.5 and E17.5 was significantly
      lower than the expected 25% (9.3 and 7.9% respectively, P < 0.001). On the first
      day of postnatal life, this was reduced further (2.4%, significantly less than
      the proportion in fetal life, P = 0.04). Pon3(+/-) animals had lower body and
      placental weights than wild-type littermates at E17.5, an effect that was
      independent of the parent of origin of the mutant allele. We then studied the
      effect of PON3 knockdown in a human cell line, A549. Stable knockdown of PON3
      using short-hairpin RNA reduced cell proliferation in 21% oxygen. We then studied
      the effect of transient knockdown of PON3 using short interfering RNA (siRNA) in
      the same cell line in low (2%) or ambient (21%) oxygen. Knockdown of PON3 using
      siRNA reduced total antioxidant capacity in 21% (P = 0.008) but not 2% oxygen. We
      conclude that the absence of Pon3 in mice resulted in increased rates of early
      fetal and neonatal death. Knockdown of PON3 in human cells reduced cell
      proliferation and total antioxidant capacity.

PMID- 21952036
TI  - Glucokinase activation repairs defective bioenergetics of islets of Langerhans
      isolated from type 2 diabetics.
AB  - It was reported previously that isolated human islets from individuals with type
      2 diabetes mellitus (T2DM) show reduced glucose-stimulated insulin release. To
      assess the possibility that impaired bioenergetics may contribute to this defect,
      glucose-stimulated respiration (Vo(2)), glucose usage and oxidation,
      intracellular Ca(2+), and insulin secretion (IS) were measured in pancreatic
      islets isolated from three healthy and three type 2 diabetic organ donors.
      Isolated mouse and rat islets were studied for comparison. Islets were exposed to
      a "staircase" glucose stimulus, whereas IR and Vo(2) were measured. Vo(2) of
      human islets from normals and diabetics increased sigmoidally from equal
      baselines of 0.25 nmol/100 islets/min as a function of glucose concentration.
      Maximal Vo(2) of normal islets at 24 mM glucose was 0.40 +/- 0.02 nmol.min(
      1).100 islets(-1), and the glucose S(0.5) was 4.39 +/- 0.10 mM. The glucose
      stimulation of respiration of islets from diabetics was lower, V(max) of 0.32 +/-
      0.01 nmol.min(-1).100 islets(-1), and the S(0.5) shifted to 5.43 +/- 0.13 mM.
      Glucose-stimulated IS and the rise of intracellular Ca(2+) were also reduced in
      diabetic islets. A clinically effective glucokinase activator normalized the
      defective Vo(2), IR, and free calcium responses during glucose stimulation in
      islets from type 2 diabetics. The body of data shows that there is a clear
      relationship between the pancreatic islet energy (ATP) production rate and IS.
      This relationship was similar for normal human, mouse, and rat islets and the
      data for all species fitted a single sigmoidal curve. The shared threshold rate
      for IS was ~13 pmol.min(-1).islet(-1). Exendin-4, a GLP-1 analog, shifted the ATP
      production-IS curve to the left and greatly potentiated IS with an ATP production
      rate threshold of ~10 pmol.min(-1).islet(-1). Our data suggest that impaired beta
      cell bioenergetics resulting in greatly reduced ATP production is critical in the
      molecular pathogenesis of type 2 diabetes mellitus.

PMID- 21952038
TI  - Short-term and long-term leptin exposure differentially affect human natural
      killer cell immune functions.
AB  - Epidemiological studies have indicated that obesity is associated with a higher
      risk for certain cancers caused by elevated levels of adipocyte-derived hormones.
      Leptin, one such hormone produced by adipocytes, is a major regulator of
      metabolism and has also been shown to modulate immunity. However, its role in
      regulating human natural killer (NK) cell functions is largely unknown. Here, we
      show that the leptin receptor (Ob-R) is expressed on 5% of NK cells isolated from
      blood donors, as measured with flow cytometry, and expression of the signal
      transducing long form of the leptin receptor Ob-Rb was confirmed with
      quantitative PCR. The Ob-R+ subpopulation displayed a lower expression of CD16, a
      cell surface receptor mediating antibody-dependent activation. Short-term
      stimulation with leptin increased IFNgamma secretion, CD69 activation marker
      expression, and cytotoxic lysis of tumor cells; this was mediated by an improved
      conjugate forming between NK cells and tumor cells as well as higher expression
      of tumor necrosis factor-related apoptosis-inducing ligand. On the contrary, long
      term incubation with leptin significantly impaired these NK cell immune functions
      and decreased cell proliferation. In addition, phosphorylation of Jak-2 after
      leptin stimulation was reduced in peripheral mononuclear blood cells from obese
      humans compared with normal-weight controls. NK cells represent an immune cell
      population that is crucial for an effective antitumor response. Here, we show
      that long-term exposure to leptin, similarly to the situation in obese
      individuals with elevated serum leptin levels, significantly impairs integral
      parts of NK cell immune functions, possibly linking leptin to increased cancer
      susceptibility in obesity.

PMID- 21952039
TI  - Overactive bladder syndrome: an underestimated long-term problem after treatment
      of patients with localized prostate cancer?
AB  - Study Type - Therapy (case series) Level of Evidence 4 What's known on the
      subject? and What does the study add? In this study we observed courses of
      micturition symptoms and differentiated degrees of symptoms for each point in
      time while also considering the impact of bothersomeness. Our data show that not
      only significantly more patients who have undergone BT suffer from OAB than those
      who have undergone RP, but also that those affected show significantly higher
      values for severity of OAB symptoms throughout the whole observation period of 36
      months. Our data analysis further shows that variability of OAB symptoms as well
      as fluctuation of severity of OAB symptoms vary to a significantly higher degree
      after BT than after RP. Looking only at mean figures at a given point in time
      clearly underestimates the underlying problem. This fact is not reflected in the
      literature. OBJECTIVE: * To look at individual courses of postoperative
      micturition symptoms, especially urgency, in patients treated either with radical
      prostatectomy (RP) or with brachytherapy (BT). PATIENTS AND METHODS: * In a
      prospective longitudinal study we investigated individual changes in micturition
      symptoms before treatment, and 6, 12, 24 and 36 months after treatment. * All
      patients received the European Organization for the Research and Treatment of
      Cancer quality-of-life questionnaire, QLQ-C30, and the International Continence
      Society male questionnaire at each assessment. * We looked at long-term results
      as well as changes in time using repeated measures analysis of variance. We
      further analysed fluctuation of symptoms using sum of changes. RESULTS: * Of the
      389 patients treated consecutively in our clinic over the last few years, 99
      patients with a mean (sd) age of 65 (6.3) years had completed all five
      questionnaires and thus were further analysed. Of these, 66 (66.7%) were treated
      with RP and 33 (33.3%) with BT. * With the exception of age, no significant
      difference was found between the treatment groups either in physical functioning
      or in prevalence and severity of overactive bladder (OAB) symptoms. * Adjusted
      for age and pretreatment symptoms in analysis of covariance, we found that there
      were statistically more symptoms of OAB 36 months after BT compared with those
      patients treated with RP (P < 0.025). Whereas 30% of patients complained about
      severe symptoms of urgency after BT, only 11% did so after RP. * Changes of
      severity of OAB symptoms over the course of time (P < 0.007) using analysis of
      repeated measures as well as variability of OAB symptoms (P < 0.033) using the
      two-sided Wilcoxon t-test were significantly higher in patients treated with BT
      than in patients treated with RP. CONCLUSIONS: * Independently of age and
      physical functioning, BT is significantly associated with higher rates of long
      term urgency symptoms, even after 3 years. * Repeated measurements show that OAB
      symptoms are highly fluctuating and that in patients treated with BT, severity of
      symptoms as well as variability of symptoms was significantly higher than in
      those patients treated with RP. * Persistent OAB seems to be an underestimated
      problem after treatment for localized prostate cancer, especially in patients
      treated with BT.

PMID- 21952040
TI  - Prolonged antispasmodic effect in isolated radial artery graft and pronounced
      platelet inhibition induced by the inodilator drug, levosimendan.
AB  - Radial artery frequently develops spasm and requires vasodilator therapy during
      coronary artery bypass graft surgery (CABG). Levosimendan was recently shown to
      oppose 5-hydroxytryptamine-induced contraction of radial artery (RA) grafts. The
      aim of the present study was to explore whether levosimendan retains its
      vasodilatory capacity following in vitro pre-incubation of RA segments with the
      inodilator. A possible cumulative effect of the drug in human platelets was also
      studied. Human isolated RA segments were pre-incubated in 0.16 MUmol/L
      levosimendan containing solution or in 0.9% NaCl, Bretschneider, 5% albumin and a
      5% human serum protein solution (Biseko) as controls for 45 min. Contractions
      were induced by three consecutive administrations of 5-hydroxytryptamine (0.31
      MUM) 45, 90 and 120 min. after exchanging the pre-incubation solutions with Krebs
      Henseleit solution, uniformly. Receptor-independent contractions (KCl, 80
      mmol/L), endothelium-dependent (acetylcholine, 1 MUmol/L) and independent
      relaxations (papaverine, 100 MUmol/L) were also investigated. Washed human
      platelets were pre-incubated with levosimendan (0.06 MUmol/L) for 2 or 15 min.
      and aggregated with thrombin (0.1 IU/mL). Contractions of RA grafts induced by 5
      hydroxytryptamine were significantly smaller 45 min. and 90 min. after the
      replacement of levosimendan with Krebs-Henseleit solution. Biseko solution also
      decreased the contraction of the graft at 45 min. Contractions did not change in
      time following the pre-incubations of radial arteries with 0.9% NaCl,
      Bretschneider and 5% albumin solutions. The grafts remained intact as assessed by
      their maximum contractions and endothelium-dependent and endothelium-independent
      relaxations at the end of the investigations. Platelets revealed larger anti
      aggregatory effect to levosimendan following the enhancement of the incubation
      time. Results indicate that the antispasmodic and anti-aggregatory effects of
      levosimendan cumulate in the vascular tissue and in platelets. The storage of RA
      with the inodilator before implantation may help to prevent the intraoperative
      spasm of the graft and also thrombotic occlusion during CABG surgery.

PMID- 21952041
TI  - In vivo von Willebrand factor size heterogeneity in spite of the clinical
      deficiency of ADAMTS-13.

PMID- 21952042
TI  - Alterations in chondroitin sulfate proteoglycan expression occur both at and far
      from the site of spinal contusion injury.
AB  - Chondroitin sulfate proteoglycans (CSPGs) present an inhibitory barrier to axonal
      growth and plasticity after trauma to the central nervous system. These
      extracellular and membrane bound molecules are altered after spinal cord
      injuries, but the magnitude, time course, and patterns of expression following
      contusion injury have not been fully described. Western blots and
      immunohistochemistry were combined to assess the expression of four classically
      inhibitory CSPGs, aggrecan, neurocan, brevican and NG2, at the lesion site and in
      distal segments of cervical and thoracic spinal cord at 3, 7, 14 and 28 days
      following a severe mid-thoracic spinal contusion. Total neurocan and the full
      length (250 kDa) isoform were strongly upregulated both at the lesion epicenter
      and in cervical and lumbar segments. In contrast, aggrecan and brevican were
      sharply reduced at the injury site and were unchanged in distal segments. Total
      NG2 protein was unchanged across the injury site, while NG2+ profiles were
      distributed throughout the lesion site by 14 days post-injury (dpi). Far from the
      lesion, NG2 expression was increased at lumbar, but not cervical spinal cord
      levels. To determine if the robust increase in neurocan at the distal spinal cord
      levels corresponded to regions of increased astrogliosis, neurocan and GFAP
      immunoreactivity were measured in gray and white matter regions of the spinal
      enlargements. GFAP antibodies revealed a transient increase in reactive astrocyte
      staining in cervical and lumbar cord, peaking at 14 dpi. In contrast, neurocan
      immunoreactivity was specifically elevated in the cervical dorsal columns and in
      the lumbar ventral horn and remained high through 28 dpi. The long lasting
      increase of neurocan in gray matter regions at distal levels of the spinal cord
      may contribute to the restriction of plasticity in the chronic phase after SCI.
      Thus, therapies targeted at altering this CSPG both at and far from the lesion
      site may represent a reasonable addition to combined strategies to improve
      recovery after SCI.

PMID- 21952043
TI  - Taurine reduces nitrosative stress and nitric oxide synthase expression in high
      glucose-exposed human Schwann cells.
AB  - The role of taurine in regulating glucose-induced nitrosative stress has been
      examined in human Schwann cells, a model for understanding the pathogenesis of
      diabetic neuropathy. Exposure to high glucose increased nitrated proteins (1.56
      fold p<0.05), inducible nitric oxide synthase (iNOS) and neuronal NOS (nNOS) mRNA
      expression (1.55 fold and 2.2 fold respectively, p<0.05 both), phospho-p38 MAPK
      (1.32 fold, p<0.05) abundance and decreased Schwann cell growth (11+/-2%,
      p<0.05). Taurine supplementation prevented high-glucose induced iNOS and nNOS
      mRNA upregulation, reduced nitrated proteins and phospho-p38 MAPK (56+/-11% and
      45+/-18% (p<0.05 both) respectively) and restored Schwann cell growth to control
      levels. High glucose and taurine treatment alone reduced phospho-p42/44 MAPK and
      phospho-AKT to below detectable levels. Treatment of human Schwann cells with
      donors of nitric oxide and peroxynitrite reduced taurine transporter (TauT)
      expression (by 35+/-5% and 29+/-7% respectively p<0.05 both) as well as the
      maximum velocity of taurine uptake (TauT Vmax). NOS inhibition prevented glucose
      mediated TauT mRNA downregulation, and restored TauT Vmax. These data demonstrate
      an important role for taurine in the prevention of nitrosative stress in human
      Schwann cells, which may have important implications for the development and
      treatment of diabetic neuropathy.

PMID- 21952044
TI  - A tiling microarray for global analysis of chloroplast genome expression in
      cucumber and other plants.
AB  - Plastids are small organelles equipped with their own genomes (plastomes).
      Although these organelles are involved in numerous plant metabolic pathways,
      current knowledge about the transcriptional activity of plastomes is limited. To
      solve this problem, we constructed a plastid tiling microarray (PlasTi
      microarray) consisting of 1629 oligonucleotide probes. The oligonucleotides were
      designed based on the cucumber chloroplast genomic sequence and targeted both
      strands of the plastome in a non-contiguous arrangement. Up to 4 specific probes
      were designed for each gene/exon, and the intergenic regions were covered
      regularly, with 70-nt intervals. We also developed a protocol for direct chemical
      labeling and hybridization of as little as 2 micrograms of chloroplast RNA. We
      used this protocol for profiling the expression of the cucumber chloroplast
      plastome on the PlasTi-microarray. Owing to the high sequence similarity of plant
      plastomes, the newly constructed microarray can be used to study plants other
      than cucumber. Comparative hybridization of chloroplast transcriptomes from
      cucumber, Arabidopsis, tomato and spinach showed that the PlasTi-microarray is
      highly versatile.

PMID- 21952045
TI  - DNA-end capping by the budding yeast transcription factor and subtelomeric
      binding protein Tbf1.
AB  - Telomere repeats in budding yeast are maintained at a constant average length and
      protected ('capped'), in part, by mechanisms involving the TG(1-3) repeat-binding
      protein Rap1. However, metazoan telomere repeats (T(2)AG(3)) can be maintained in
      yeast through a Rap1-independent mechanism. Here, we examine the dynamics of
      capping and telomere formation at an induced DNA double-strand break flanked by
      varying lengths of T(2)AG(3) repeats. We show that a 60-bp T(2)AG(3) repeat array
      induces a transient G2/M checkpoint arrest, but is rapidly elongated by
      telomerase to generate a stable T(2)AG(3)/TG(1-3) hybrid telomere. In contrast, a
      230-bp T(2)AG(3) array induces neither G2/M arrest nor telomerase elongation.
      This capped state requires the T(2)AG(3)-binding protein Tbf1, but is independent
      of two Tbf1-interacting factors, Vid22 and Ygr071c. Arrays of binding sites for
      three other subtelomeric or Myb/SANT domain-containing proteins fail to display a
      similar end-protection effect, indicating that Tbf1 capping is an evolved
      function. Unexpectedly, we observed strong telomerase association with non
      telomeric ends, whose elongation is blocked by a Mec1-dependent mechanism,
      apparently acting at the level of Cdc13 binding.

PMID- 21952046
TI  - The complex transcription regulatory landscape of our genome: control in three
      dimensions.
AB  - The non-coding part of our genome contains sequence motifs that can control gene
      transcription over distance. Here, we discuss functional genomics studies that
      uncover and characterize these sequences across the mammalian genome. The picture
      emerging is of a genome being a complex regulatory landscape. We explore the
      principles that underlie the wiring of regulatory DNA sequences and genes. We
      argue transcriptional control over distance can be understood when considering
      action in the context of the folded genome. Genome topology is expected to differ
      between individual cells, and this may cause variegated expression. High
      resolution three-dimensional genome topology maps, ultimately of single cells,
      are required to understand the cis-regulatory networks that underlie cellular
      transcriptomes.

PMID- 21952047
TI  - PKC alpha regulates Sendai virus-mediated interferon induction through HDAC6 and
      beta-catenin.
AB  - Recognition of viral RNA by cytoplasmic retinoic acid inducible gene I (RIG-I)
      like receptors initiates signals leading to the induction of type I interferon
      (IFN) transcription via transcription factors such as interferon regulatory
      factor 3 (IRF3) and nuclear factor kappaB (NF-kappaB). Here, we describe a new
      signalling pathway that involves protein kinase C alpha (PKCalpha), histone
      deacetylase 6 (HDAC6) and beta-catenin (beta-catenin), which is essential for IFN
      gene induction following virus infection. Knockdown of PKCalpha in various human
      cells, including primary cells, inhibited Sendai virus (SeV)-mediated IFN
      induction and enhanced virus replication. In the absence of this pathway IRF3
      becomes activated, but does not bind to its promoter and is thus unable to
      support transcription. Mechanistically, SeV infection induced the activation of
      PKCalpha, which promoted its interaction with HDAC6 and enhanced its
      deacetylation activity in a phosphorylation-dependent manner. Further downstream,
      HDAC6 caused deacetylation of beta-catenin and enhanced its nuclear translocation
      and promoter binding. In the nucleus, beta-catenin acted as a co-activator for
      IRF3-mediated transcription. Our findings suggest an important role of a novel
      signalling pathway mediated by PKCalpha-HDAC6-beta-catenin in controlling IRF3
      mediated transcription.

PMID- 21952048
TI  - Lats2 kinase potentiates Snail1 activity by promoting nuclear retention upon
      phosphorylation.
AB  - Snail1 is a central regulator of epithelial cell adhesion and movement in
      epithelial-to-mesenchymal transitions (EMTs) during embryo development; a process
      reactivated during cancer metastasis. While induction of Snail1 transcription
      precedes EMT induction, post-translational regulation of Snail1 is also critical
      for determining Snail1's protein level, subcellular localization, and capacity to
      induce EMT. To identify novel post-translational regulators of Snail1, we
      developed a live cell, bioluminescence-based screen. From a human kinome RNAi
      screen, we have identified Lats2 kinase as a novel regulator of Snail1 protein
      level, subcellular localization, and thus, activity. We show that Lats2 interacts
      with Snail1 and directly phosphorylates Snail1 at residue T203. This occurs in
      the nucleus and serves to retain Snail1 in the nucleus thereby enhancing its
      stability. Lats2 was found to positively influence cellular EMT and tumour cell
      invasion, in a Snail1-dependent manner. Indeed during TGFbeta-induced EMT Lats2
      is activated and Snail1 phosphorylated at T203. Analysis in mouse and zebrafish
      embryo development confirms that Lats2 acts as a positive modulator of Snail1
      protein level and potentiates its in vivo EMT activity.

PMID- 21952050
TI  - Insights into transport mechanism from LeuT engineered to transport tryptophan.
AB  - LeuT is a bacterial homologue of the neurotransmitter:sodium symporter (NSS)
      family and, being the only NSS member to have been structurally characterized by
      X-ray crystallography, is a model protein for studying transporter structure and
      mechanism. Transport activity in LeuT was hypothesized to require structural
      transitions between open-to-out and occluded conformations dependent upon
      protein:ligand binding complementarity. Here, using crystallographic and
      functional analysis, we show that binding site modification produces changes in
      both structure and activity that are consistent with complementarity-dependent
      structural transitions to the occluded state. The mutation I359Q converts the
      activity of tryptophan from inhibitor to transportable substrate. This mutation
      changes the local environment of the binding site, inducing the bound tryptophan
      to adopt a different conformer than in the wild-type complex. Instead of trapping
      the transporter open, tryptophan binding now allows the formation of an occluded
      state. Thus, transport activity is correlated to the ability of the ligand to
      promote the structural transition to the occluded state, a step in the transport
      cycle that is dependent on protein:ligand complementarity in the central binding
      site.

PMID- 21952051
TI  - Upregulation of nestin protects podocytes from apoptosis induced by puromycin
      aminonucleoside.
AB  - BACKGROUND: Nestin is an intermediate filament protein widely used as a marker of
      stem cells or progenitor cells. Nestin is also highly expressed in the glomerular
      podocyte, a type of terminally differentiated epithelial cell. Little is known
      about the significance of nestin in podocytes. METHODS: Puromycin aminonucleoside
      (PAN) was injected into the rats to produce a PAN nephrosis model. Transmission
      electronic microscopy and terminal dUTP nick end-labeling assay were used to
      examine the podocyte foot process (FP) effacement and apoptosis, respectively. A
      mouse podocyte cell line was cultured and incubated with PAN. Immunoblot was used
      to examine the level of nestin expression both in vivo and in vitro. Enhanced
      green fluorescence protein-tagged plasmids containing nestin shRNA were
      transfected into the cultured podocytes to silence nestin expression. F-actin
      arrangement within cultured podocytes was investigated by immunofluorescence,
      while the apoptosis rate was examined by both Hoechst stain and flow cytometry.
      RESULTS: In the PAN-induced rat nephrosis model, podocyte nestin expression was
      increased in the absence of apparent podocyte apoptosis, even though the FP was
      significantly effaced. In the cultured mouse podocytes, PAN upregulated nestin
      expression in a time-dependent manner within 24 h of treatment. Notably, no
      significant apoptosis occurred, however knocking down nestin expression resulted
      in a remarkable derangement of actin cytoskeleton and an increase in apoptosis in
      the cultured podocytes 24 h after being incubated with PAN. CONCLUSIONS:
      Upregulation of nestin expression during PAN nephrosis could protect podocytes
      from apoptosis and that this process is mediated by maintaining the regular
      arrangement of actin cytoskeleton.

PMID- 21952052
TI  - Comparison of home and away-from-home physical activity using accelerometers and
      cellular network-based tracking devices.
AB  - BACKGROUND: Measuring physical at home and away from home is essential for
      assessing health and well-being, and could help design interventions to increase
      physical activity. Here, we describe how physical activity at home and away from
      home can be quantified by combining information from cellular network-based
      tracking devices and accelerometers. METHODS: Thirty-five working adults wore a
      cellular network-based tracking device and an accelerometer for 6 consecutive
      days and logged their travel away from home. Performance of the tracking device
      was determined using the travel log for reference. Tracking device and
      accelerometer data were merged to compare physical activity at home and away from
      home. RESULTS: The tracking device detected 98.6% of all away-from-home
      excursions, accurately measured time away from home and demonstrated few
      prolonged signal drop-out periods. Most physical activity took place away from
      home on weekdays, but not on weekends. Subjects were more physically active per
      unit of time while away from home, particularly on weekends. CONCLUSIONS:
      Cellular network-based tracking devices represent an alternative to global
      positioning systems for tracking location, and provide information easily
      integrated with accelerometers to determine where physical activity takes place.
      Promoting greater time spent away from home may increase physical activity.

PMID- 21952049
TI  - The Cutoff protein regulates piRNA cluster expression and piRNA production in the
      Drosophila germline.
AB  - In a broad range of organisms, Piwi-interacting RNAs (piRNAs) have emerged as
      core components of a surveillance system that protects the genome by silencing
      transposable and repetitive elements. A vast proportion of piRNAs is produced
      from discrete genomic loci, termed piRNA clusters, which are generally embedded
      in heterochromatic regions. The molecular mechanisms and the factors that govern
      their expression are largely unknown. Here, we show that Cutoff (Cuff), a
      Drosophila protein related to the yeast transcription termination factor Rai1, is
      essential for piRNA production in germline tissues. Cuff accumulates at
      centromeric/pericentromeric positions in germ-cell nuclei and strongly
      colocalizes with the major heterochromatic domains. Remarkably, we show that Cuff
      is enriched at the dual-strand piRNA cluster 1/42AB and is likely to be involved
      in regulation of transcript levels of similar loci dispersed in the genome.
      Consistent with this observation, Cuff physically interacts with the
      Heterochromatin Protein 1 (HP1) variant Rhino (Rhi). Our results unveil a link
      between Cuff activity, heterochromatin assembly and piRNA cluster expression,
      which is critical for stem-cell and germ-cell development in Drosophila.

PMID- 21952053
TI  - "A morning since eight of just pure grill": a multischool qualitative study of
      student abuse.
AB  - PURPOSE: Previous medical student abuse research employed quantitative surveys
      that failed to explore factors thought to contribute to abuse and students'
      actions in the face of abuse. This study examined medical student abuse
      narratives to identify types of perceived abuse, factors cited by students as
      contributing to abuse, and students' actions at the time of abuse. METHOD: A
      qualitative design was adopted employing 22 individual and 32 group interviews to
      elicit narratives of professionalism dilemmas from 200 medical students at two 5
      year undergraduate programs and one 4-year graduate entry program (England,
      Wales, and Australia) between 2007 and 2009. Thematic analysis of abuse
      narratives was conducted. RESULTS: Of 833 professionalism dilemma narratives, 86
      (10%) involved perceived medical student abuse. Within these narratives, students
      reported mostly covert, status-related abuse, direct verbal abuse, and sexual
      harassment and discrimination. Some narrators described multiple factors
      contributing to abuse (individual, work, and/or organization); most cited factors
      focusing on individuals. Despite the abuse typically recounted with negative
      emotion, few participants reported resisting at the time of abuse by challenging
      or reporting the perpetrator. Participants gave a variety of reasons for this
      inaction (e.g., anxiety about receiving bad marks from the perpetrator) and for
      resisting (e.g., the abuse was affecting their education negatively).
      CONCLUSIONS: Although narratives focused predominantly on individual factors
      contributing to abuse and responses to abuse, educators should focus on the
      dynamic interplay between individual and organizational factors to combat abuse.
      Several opportunities to mitigate this continuing blight on the conscience of the
      profession are described.

PMID- 21952054
TI  - Going beyond Kirkpatrick in evaluating a clinician scientist program: it's not
      "if it works" but "how it works".
AB  - PURPOSE: To explore how the Canadian Child Health Clinician Scientist Program
      (CCHCSP) works to achieve prearticulated and emergent outcomes. METHOD: In 2009,
      after gaining ethical approval from the Hospital for Sick Children, the authors
      examined quantitative data (e.g., participation in curriculum elements) to ensure
      sufficient exposure by trainees to the program and quantitative outputs (e.g.,
      publications) to measure achievement of CCHCSP goals. They identified emergent
      outcomes through grouping and analyzing qualitative data generated through
      interviews with program graduates. Then, to explore possible theoretical
      explanations for the emergent findings, the authors conducted a literature
      review. RESULTS: Graduates participated in high rates in each component of the
      CCHCSP and produced publications, presented research, and received funding.
      Interview data revealed an unexpected outcome: that the CCHCSP helped graduates
      to form new professional identities. These data, along with theoretical
      assumptions from Ibarra's theory on professional identity change, informed a new
      theory or model for the CCHCSP. CONCLUSIONS: Early investment in building a
      program's logic model is invaluable for understanding program goals and for
      guiding program planning and development. Both employing a strategy that captures
      emergent program outcomes and investigating (e.g., through a literature search)
      why and how the program actually works to arrive at these outcomes informs the
      development and evaluation of future program offerings and may, as in the case of
      the CCHCSP, offer a new program model or theory.

PMID- 21952055
TI  - Factors affecting weight counseling attitudes and behaviors among U.S. medical
      students.
AB  - PURPOSE: To identify the factors associated with perceived relevance and reported
      frequency of weight counseling among medical students. METHOD: The authors
      surveyed all medical students in the Class of 2003 at 16 U.S. medical schools
      during first-year orientation (1999), orientation to wards (2000-2001), and
      fourth year (2002-2003). RESULTS: Across the three time points, response rates
      were, respectively, 89% (1,846/2,080), 82% (1,630/1,982), and 77% (1,469/1,901);
      a total of 2,316 medical students participated. More than half of the students
      felt that weight counseling was highly relevant to their intended practice
      (respectively, 63% [1,149/1,812], 70% [1,050/1,509], and 54% [717/1,329]). Among
      fourth-year students, 25% (350/1,393) reported that they "usually-always"
      provided weight counseling to general medicine patients. Perceived relevance
      peaked at orientation to wards (odds ratio [OR]=1.88), then declined to initial
      levels.Greater school support for health promotion was positively associated with
      high counseling frequency (OR=1.06). Students interested in non-primary-care
      specialties were less likely than others to consider weight counseling highly
      relevant (OR=0.59) or, in their fourth year, to provide it to patients (OR=0.50).
      Finally, higher personal fruit/vegetable consumption and confidence that this
      intake would increase were positively associated with high perceived relevance
      (both OR=1.07) and frequency of weight counseling (OR=1.09 and 1.16,
      respectively). CONCLUSIONS: The majority of medical students consider weight
      counseling relevant to their intended careers. Promoting healthy personal
      behaviors and encouraging acquisition of skills in weight management across all
      specialties would likely improve clinical practice.

PMID- 21952056
TI  - Professional challenges of non-U.S.-born international medical graduates and
      recommendations for support during residency training.
AB  - PURPOSE: Despite a long history of international medical graduates (IMGs) coming
      to the United States for residencies, little research has been done to find
      systematic ways in which residency programs can support IMGs during this
      vulnerable transition. The authors interviewed a diverse group of IMGs to
      identify challenges that might be eased by targeted interventions provided within
      the structure of residency training. METHOD: In a qualitative study conducted
      between March 2008 and April 2009, the authors contacted 27 non-U.S.-born IMGs
      with the goal of conducting qualitative interviews with a purposeful sample. The
      authors conducted in-person, in-depth interviews using a standardized interview
      guide with potential probes. All participants were primary care practitioners in
      New York, New Jersey, or Connecticut. RESULTS: A total of 25 IMGs (93%)
      participated. Interviews and subsequent analysis produced four themes that
      highlight challenges faced by IMGs: (1) Respondents must simultaneously navigate
      dual learning curves as immigrants and as residents, (2) IMGs face insensitivity
      and isolation in the workplace, (3) IMGs' migration has personal and global
      costs, and (4) IMGs face specific needs as they prepare to complete their
      residency training. The authors used these themes to inform recommendations to
      residency directors who train IMGs. CONCLUSIONS: Residency is a period in which
      key elements of professional identity and behavior are established. IMGs are a
      significant and growing segment of the physician workforce. Understanding
      particular challenges faced by this group can inform efforts to strengthen
      support for them during postgraduate training.

PMID- 21952057
TI  - Effect of educational interventions and medical school policies on medical
      students' attitudes toward pharmaceutical marketing practices: a multi
      institutional study.
AB  - PURPOSE: To determine the effect of educational interventions on medical
      students' attitudes toward pharmaceutical industry marketing practices and
      whether restrictive medical school policies governing medicine-industry
      interactions are associated with student support for banning such interactions.
      METHOD: Prospective cohort study involving the graduating classes of 2009
      (intervention, n=474) and 2010 (control, n=459) at four U.S. medical schools.
      Intervention students experienced a former pharmaceutical representative's
      presentation, faculty debate, and a Web-based course. Both groups completed
      baseline and follow-up attitude surveys about pharmaceutical marketing. RESULTS:
      A total of 482 students (51.6%) completed both surveys. In regression analyses,
      intervention students were more likely than control students to think that
      physicians are strongly or moderately influenced by pharmaceutical marketing (OR,
      2.29; 95% CI, 1.46-3.59) and believed they would be more likely to prescribe a
      company's drug if they accepted that company's gifts and food (OR, 1.68; 95% CI,
      1.12-2.52). Intervention students were more likely to support banning
      interactions between pharmaceutical representatives and students (OR, 4.82; 95%
      CI, 3.02-7.68) and with physicians (OR, 6.88; 95% CI, 4.04-11.70). Students from
      schools with more restrictive policies were more likely to support banning
      interactions between pharmaceutical representatives and students (OR, 1.99; 95%
      CI, 1.26-3.16) and with physicians (OR, 3.44; 95% CI, 2.05-5.79). CONCLUSIONS:
      Education about pharmaceutical marketing practices and more restrictive policies
      governing medicine-industry interactions seem to increase medical students'
      skepticism about the appropriateness of such marketing practices and disapproval
      of pharmaceutical representatives in the learning environment.

PMID- 21952058
TI  - Perspective: Creating the next generation of general internists: a call for
      medical education reform.
AB  - The United States is faced with an increasing shortage of physicians in the
      primary care workforce. The number of medical school graduates selecting careers
      in primary care internal medicine has fallen dramatically since 1985. Although
      political, financial, and organizational reform of the medical system is
      necessary, these changes will address only part of the problem. Endeavors
      designed to ameliorate this current crisis in primary care practice must also
      address the education and training of future primary care internists. Learners
      require specialized training in primary care internal medicine to be able to
      provide high-quality, patient-centered, outcome-oriented care. This article
      examines the impact of educational interventions in undergraduate medical
      education (UME) and graduate medical education (GME) on primary care internal
      medicine career choice and makes suggestions for future educational changes.
      Suggested UME changes include providing early longitudinal clinical experiences
      and providing the option for an integrated ambulatory third year of training.
      Suggested GME changes include early, sustained exposure to general internal
      medicine and differentiated training tracks for residents interested in primary
      care. Key among these changes are that medical students and residents must have
      adequate mentorship from primary care internists and clinical experiences in
      highly functioning primary care settings established as patient-centered medical
      homes. Academic centers have a unique opportunity to contribute to these
      imperatives by reengineering the practice of primary care in a way that embodies
      the core values of effective, patient-centered care.

PMID- 21952059
TI  - Going MAD: development of a "matrix academic division" to facilitate translating
      research to personalized medicine.
AB  - Personalized medicine integrates an individual's genetic and other information
      for the prevention or treatment of complex disorders, and translational research
      seeks to identify those data most important to disease processes based on
      observations at the bench and the bedside. To understand complex disorders such
      as chronic pancreatitis, inflammatory bowel disease, liver cirrhosis, and other
      idiopathic chronic inflammatory diseases, physician-scientists must
      systematically collect data on relevant risks, clinical status, biomarkers, and
      outcomes. The author describes a "matrix academic division" (MAD), a highly
      effective academic program created at the University of Pittsburgh School of
      Medicine and the University of Pittsburgh Medical Center using translational
      research to rapidly develop personalized medicine for digestive diseases. MAD is
      designed to capture patient-specific data and biologic samples for analysis of
      steps in a complex process (reverse engineering), reconstructing the system
      conceptually and mathematically (disease modeling), and deciphering disease
      mechanism in individual patients to predict the effects of interventions
      (personalized medicine). MAD draws on the expertise of the medical school's and
      medical center's physician-scientists to translate essential disease information
      between the bed and the bench and to communicate with researchers from multiple
      domains, including epidemiology, genetics, cell biology, immunology, regenerative
      medicine, neuroscience, and oncology. The author illustrates this approach by
      describing its successful application to the reverse engineering of chronic
      pancreatitis.

PMID- 21952060
TI  - Perspective: Leveraging the health care workforce: what do we need and what
      educational system will get us there?
AB  - Shortages of 100,000 physicians and up to one million nurses are projected in the
      next 10 years. If these statistics are close to true, medical schools would need
      a 100% increase in graduates over the next 4 years, and nursing schools a 100%
      increase over the next 13 years. These calculations are instructive in that they
      demonstrate the absurdity of expecting schools to provide these sorts of
      increases in that time frame. Other solutions must be considered. For instance,
      do doctors and nurses need to do everything they are currently called on to do?
      Could not other members of the health care workforce, such as well-trained lay
      workers, be leveraged to do some of the more routine work, freeing medical
      professionals to perform their unique roles? How is such a workforce built, and
      how shall learners be educated to fill those needs? This article presents a
      hypothetical model that could be implemented based on carefully researched pilots
      to meet health care education needs. The model features three essential
      components: (1) a school for the public in which lay teachers develop curricula
      with members of the public, for example, about how to incentivize healthy
      behavior, (2) a college for health as part of a university with interdisciplinary
      teaching, where patients, faculty members, and students interact in each of the
      schools and learn together, and (3) the most effective and efficient nursing and
      medical school curricula, developed together based on evidence of what the
      student needs to know.

PMID- 21952061
TI  - Similarities and differences in the career trajectories of male and female career
      development award recipients.
AB  - PURPOSE: To examine the careers of career development award recipients. METHOD:
      In 2009, a postal survey was conducted of 818 recipients of K08 and K23 awards in
      2000-2001 to examine career paths and personal characteristics. RESULTS: Of 589
      respondents (72% response rate), 211 (35.9%) were female. Women were less likely
      to have children (P<.001) than men. The vast majority of respondents (89.6%)
      remained in academic medicine. Among those, over three-quarters continued to
      spend significant time on research. On univariate analysis, women were not
      significantly less likely to report promotion, leadership positions, or
      application for R01 grants. They were less likely to have received an R01
      (P=.006) and to perceive themselves as successful (P=.002), and they published
      fewer papers (P=.001). Overall, 118 women (55.9%) and 274 men (72.5%) met at
      least one of the following criteria for success: serving as principal
      investigator on an R01 or grants>$1,000,000 since K award receipt, publishing at
      least 35 publications since K award year, or serving as dean, department chair,
      or division chief. In a multivariate model, gender (odds ratio 1.72, P=.003) was
      associated with the likelihood of success by this definition, and analysis
      revealed no significant interactions (including with parental status).
      CONCLUSIONS: Most of these promising investigators of both genders remained in
      academia and received promotions. However, gender differences in success existed,
      unrelated to parental status, suggesting a need for ongoing investigation of the
      causes of gender differences in academic medical careers.

PMID- 21952062
TI  - Medical student and faculty perceptions of volunteer outpatients versus simulated
      patients in communication skills training.
AB  - PURPOSE: To determine whether medical students and faculty perceive differences
      in the effectiveness of interactions with real patients versus simulated patients
      (SPs) in communication skills training. METHOD: In 2008, the authors recruited
      volunteer outpatients (VOs) from the Johns Hopkins University School of Medicine
      internal medicine practice to participate in communication skills training for
      all first-year medical students. VOs and SPs were assigned to clinic rooms in the
      simulation center. Each group of five students and its preceptor rotated through
      randomly assigned rooms on two of four session days; on both days, each student
      interviewed one patient for 15 minutes, focusing on past medical and family
      history or social history. Patients used their own histories, not scripts;
      students were not blinded to patient type. Students and faculty then rated
      aspects of the interview experience. Generalized linear latent and mixed-models
      analysis was used to compare ratings of communication skills training with VOs
      versus SPs. RESULTS: All 121 first-year students participated in 242 interviews,
      resulting in 237 usable questionnaires (98%). They rated their experiences with
      VOs significantly higher than those with SPs on comfort, friendliness, amount of
      learning, opportunity to build relationships, and overall meeting of
      communication skills training needs. The 24 faculty preceptors' ratings of the
      242 interactions did not differ significantly between VOs and SPs. CONCLUSIONS:
      Use of VOs was well received by students and faculty for teaching communication
      skills. Expanding and further studying VOs' participation will allow greater
      understanding of their potential role in communication skills training of
      preclinical medical students.

PMID- 21952063
TI  - Relationship of pass/fail grading and curriculum structure with well-being among
      preclinical medical students: a multi-institutional study.
AB  - PURPOSE: Psychological distress is common among medical students. Curriculum
      structure and grading scales are modifiable learning environment factors that may
      influence student well-being. The authors sought to examine relationships among
      curriculum structures, grading scales, and student well-being. METHOD: The
      authors surveyed 2,056 first- and second-year medical students at seven U.S.
      medical schools in 2007. They used the Perceived Stress Scale, Maslach Burnout
      Inventory, and Medical Outcomes Study Short Form (SF-8) to measure stress,
      burnout, and quality of life, respectively. They measured curriculum structure
      using hours spent in didactic, clinical, and testing experiences. Grading scales
      were categorized as two categories (pass/fail) versus three or more categories
      (e.g., honors/pass/fail). RESULTS: Of the 2,056 students, 1,192 (58%) responded.
      In multivariate analyses, students in schools using grading scales with three or
      more categories had higher levels of stress (beta 2.65; 95% CI 1.54-3.76,
      P<.0001), emotional exhaustion (beta 5.35; 95% CI 3.34-7.37, P<.0001), and
      depersonalization (beta 1.36; 95% CI 0.53-2.19, P=.001) and were more likely to
      have burnout (OR 2.17; 95% CI 1.41-3.35, P=.0005) and to have seriously
      considered dropping out of school (OR 2.24; 95% CI 1.54-3.27, P<.0001) compared
      with students in schools using pass/fail grading. There were no relationships
      between time spent in didactic and clinical experiences and well-being.
      CONCLUSIONS: How students are evaluated has a greater impact than other aspects
      of curriculum structure on their well-being. Curricular reform intended to
      enhance student well-being should incorporate pass/fail grading.

PMID- 21952065
TI  - Influencing residency choice and practice location through a longitudinal rural
      pipeline program.
AB  - PURPOSE: The University of Missouri School of Medicine developed the Rural Track
      Pipeline Program (MU-RTPP) to increase the supply and retention of rural
      physicians statewide. The MU-RTPP features a preadmissions program for rural
      students (Rural Scholars), a Summer Community Program for rising second-year
      students, a six-month Rural Track Clerkship (RTC) Program for third-year
      students, and a Rural Track Elective Program for fourth-year students. The
      purpose of this study is to report the specialty choices and first practice
      locations of Rural Scholars, RTC-only participants, and Rural Track Clerkship
      Plus (RTC+) participants (students who participated in the RTC Program plus an
      additional MU-RTPP component). METHOD: The authors compared the residency
      specialty choices of 48 Rural Scholars (tracked since 2002) with those of 506
      nonparticipants and the residency specialty choices of 83 RTC participants and 75
      RTC+ participants (tracked since 1997) with those of 840 nonparticipants. The
      authors calculated the relative risk (RR) for the likelihood of participants
      matching into primary care compared with nonparticipants and analyzed first
      practice location. RESULTS: Rural Scholars were more than twice as likely to
      match into family medicine (RR=2.6; 95% confidence interval 1.5-4.4). RTC and
      RTC+ participants entered primary care, especially family medicine, at rates
      significantly higher than nonparticipants. Over 57% of students who participated
      in the RTC program (and potentially other MU-RTPP offerings) chose a rural
      location for their first practice. CONCLUSIONS: The longitudinal MU-RTPP
      successfully recruits students for rural and primary care practice to address the
      health care needs of Missouri.

PMID- 21952064
TI  - The prevalence and economic impact of low-enrolling clinical studies at an
      academic medical center.
AB  - PURPOSE: The authors assessed the prevalence and associated economic impact of
      low-enrolling clinical studies at a single academic medical center. METHOD: The
      authors examined all clinical studies receiving institutional review board (IRB)
      review between FY2006 and FY2009 at Oregon Health & Science University (OHSU) for
      recruitment performance and analyzed them by type of IRB review (full-board,
      exempt, expedited), funding mechanism, and academic unit. A low-enrolling study
      included those with zero or one participant at the time of study termination. The
      authors calculated the costs associated with IRB review, financial setup,
      contract negotiation, and department study start-up activities and the total
      economic impact on OHSU of low-enrolling studies for FY2009. RESULTS: A total of
      837 clinical studies were terminated during the study period, 260 (31.1%) of
      which were low-enrolling. A greater proportion of low-enrolling studies were
      government funded than industry funded (P=.006). The authors found significant
      differences among the various academic units with respect to percentages of low
      enrolling studies (from 10% to 67%). The uncompensated economic impact of low
      enrolling studies was conservatively estimated to be nearly $1 million for
      FY2009. CONCLUSIONS: A substantial proportion of clinical studies incurred high
      institutional and departmental expense but resulted in little scientific benefit.
      Although a certain percentage of low-enrolling studies can be expected in any
      research organization, the overall number of such studies must be managed to
      reduce the aggregate costs of conducting research and to maximize research
      opportunities. Effective, proactive interventions are needed to address the
      prevalence and impact of low enrollment.

PMID- 21952066
TI  - Patient safety stories: a project utilizing narratives in resident training.
AB  - Incident reports have traditionally been the vehicle for identifying, assessing,
      and responding to quality gaps in hospitals. Yet because of a variety of
      barriers, residents often fail to participate in this formal process. The authors
      created a project to engage residents in incident reporting through the use of an
      online, anonymous narrative format, faculty-facilitated discussion groups, and
      involvement of patient safety officers in the educational process. During three
      months, 36 residents submitted a total of 79 stories about patient care that did
      not "go as intended." The authors reviewed and scored each story for contributing
      factors and outcomes. The residents met monthly in small groups with trained
      faculty facilitators to analyze the stories, which were also shared with the
      patient safety officers. The stories, narratives of both personal involvement and
      observed events, ranged from near-misses to sentinel events. Key contributing
      factors included lapses of professionalism, decision errors,
      communication/information mishaps, transition mix-ups, and workload difficulties.
      The narrative format proved a feasible tool for collecting significant,
      previously unrecognized patient safety issues. Internal medicine residents were
      willing to discuss gaps in care when given the tools and opportunity for
      anonymous storytelling and blame-free dialogue.

PMID- 21952067
TI  - The effect of patient feedback on physicians' consultation skills: a systematic
      review.
AB  - PURPOSE: The effect of patient feedback interventions as a method of improving
      physicians' consultation (i.e., communication, interpersonal) skills is
      equivocal; research is scarce, and methods and rigor vary. The authors conducted
      this systematic review to analyze the educational effect of feedback from real
      patients on physicians' consultation skills at the four Kirkpatrick levels.
      METHOD: The authors searched five databases (PubMed, EMBASE, Cochrane, PsycInfo,
      ERIC; April 2010). They included empirical studies of all designs (randomized
      controlled, quasi-experimental, cross-sectional, and qualitative) if the studies
      concerned physicians in general health care who received formal feedback
      regarding their consultation skills from real patients. The authors have briefly
      described aspects of the included studies, analyzed their quality, and examined
      their results by Kirkpatrick educational effect level. RESULTS: The authors
      identified 15 studies (10 studies in primary care; 5 in other specialties) in
      which physicians received feedback in various ways (e.g., aggregated patient
      reports or educator-mediated coaching sessions), conducted in the United States,
      the Netherlands, the United Kingdom, Australia, and Canada. All studies that
      assessed level 1 (valuation), level 2 (learning), and level 3 (intended behavior)
      demonstrated positive results; however, only four of the seven studies that
      assessed level 4 (change in actual performance or results) found a beneficial
      effect. CONCLUSIONS: Some evidence for the effectiveness of using feedback from
      real patients to improve knowledge and behavior exists; however, before
      implementing patient feedback into training programs, educators and policy makers
      should realize that the evidence for effecting actual improvement in physicians'
      consulting skills is rather limited.

PMID- 21952068
TI  - A study on sexual function of men with anterior urethral stricture before and
      after treatment.
AB  - INTRODUCTION: Male urethral reconstruction for anterior urethral stricture has
      become increasingly popular and effective. Little is known about its potential
      impact on subsequent sexual performance. PATIENTS AND METHODS: Thirty-four
      patients of anterior urethral stricture disease were studied from January 2008 to
      November 2009. The data were collected before surgery and at a follow-up of 3
      months after completing the treatment. Evaluation of sexual function was done
      using O'Leary's Brief Male Sexual Function Inventory. RESULTS: Patients were
      divided into two categories: <40 and >40 years of age. Younger patients had more
      improvement in ejaculatory function and overall satisfaction after surgery than
      elderly. Elderly males had lower sexual drive scores. Patients with traumatic
      stricture had significant improvement in ejaculation and overall satisfaction.
      Patients without history of prior optical internal urethrotomy or dilatations
      reported a significant improvement in their ejaculatory function and overall
      satisfaction. CONCLUSION: Erectile dysfunction is not significant after anterior
      urethral reconstruction. The improvement is most pronounced in ejaculation and
      overall satisfaction, which was mostly appreciated by younger men. A successful
      urethral reconstructive procedure leads to rehabilitation of the patient back
      into a healthy sexual life. Dorsomedial dissection of bulbar urethra should be
      limited and cautery use should be minimized in that area.

PMID- 21952069
TI  - Targeted therapy for advanced renal cell cancer (RCC): a Cochrane systematic
      review of published randomised trials.
AB  - OBJECTIVE: To estimate the effects of drugs with molecular targets on patients
      with advanced renal cell cancer (RCC). PATIENTS AND METHODS: MEDLINE, EMBASE, and
      the Cochrane Collaboration Library were systematically searched on-line through
      to June 2011 to identify eligible randomised trials. We also searched abstract
      reports from major oncology and urology meetings. We included randomised trials
      that tested a targeted agent and reported at least one outcome by allocation on
      an intent-to-treat basis. Completeness of ascertainment and risk of bias were
      assessed. Our primary outcome was progression-free survival (PFS). RESULTS: In
      all, 28 studies met our inclusion criteria and 10 were placebo-controlled. Two
      studies were too small to assess, and five early studies used nonspecific anti
      angiogenic agents with poor activity. In all, 15 studies, in 5587 patients,
      tested anti-vascular epithelial growth factor (VEGF) agents: bevacizumab (BEV),
      sorafenib, sunitinib, pazopanib, tivozanib, or axitinib. Three studies, in 1147
      patients, tested the mammalian target of rapamycin (mTOR) inhibitors,
      temsirolimus or everolimus. Two studies included epidermal growth factor receptor
      (EGFR) inhibitors, and one tested the combination of temsirolimus plus BEV. In
      treatment-naive patients with mostly good-moderate prognostic risk, in separate
      trials oral sunitinib (one trial) and intravenous BEV plus subcutaneousinterferon
      alpha (two trials) improved PFS compared with the previous standard of care
      interferon-alpha within randomised phase III trials. Sorafenib did not improve
      PFS over interferon-alpha in the first-line setting and the addition of cytokines
      did not improve sorafenib efficacy. In poor-risk patients, the mTOR inhibitor
      temsirolimus improved PFS and overall survival (OS). The studies of other VEGF
      inhibitors have used placebo controls no longer appropriate in this setting,
      although pazopanib is an approved option. Several trials examined agents in the
      second-line setting. After cytokine therapy, sorafenib (one study) and pazopanib
      (one study) prolonged PFS over placebo. A preliminary report of the
      investigational VEGF receptorinhibitor axitinib gave superior PFS to sorafenib
      after either prior cytokine or prior sunitinib treatment. After cancer
      progression <=6 months of sunitinib and/or sorafenib therapy, everolimusprolonged
      PFS. OS was marginally improved in several studies. A more substantial effect on
      OS may have been diluted by crossover from control therapy to the investigational
      arm and/or by other anti-angiogenic agents after trial closure. Patient-reported
      outcomes were considered unreliable in trials without 'blinding'. A clear cell
      RCC (ccRCC) component was required for most trials, and information for non
      ccRCCs is consequently limited CONCLUSIONS: Agents targeting VEGF and mTOR
      pathways improve PFS in both first-line and second-line settings. These
      treatments rarely yield complete responses and thus are not curative. No placebo
      controlled trial has reported a health-related quality of life benefit.

PMID- 21952070
TI  - Effect of disorder on the magnetic properties of a partially filled skutterudite.
AB  - The magnetic properties of the partially filled skutterudite Eu(0.5)Co(4)Sb(12)
      are investigated by a model Hamiltonian, with special emphasis on the effect of
      ordering and disordering occupancy of the filler atoms Eu on the magnetic
      properties. The magnetization, magnetic specific heat and entropy are calculated
      within the mean-field approximation. By introducing the position disorder of the
      filler atoms, the critical temperature T(C) above which the magnetization
      disappears is changed. The magnetization curve near T(C) also becomes concave
      compared to the convex magnetization of the ordered system. The filler
      disordering also leads to a kink in the isothermal magnetization curve and a
      valley in the magnetic specific heat near T(C). The effective magnetic field
      acting on the localized spin of the filler atoms has a competitive effect with
      the disorder and therefore makes the valley disappear.

PMID- 21952071
TI  - Reorganization of motor system in Parkinson's disease.
AB  - BACKGROUND/AIMS: We investigated adaptive reorganization in Parkinson's disease
      (PD) by fMRI using a passive movement task and compared the brain activation
      patterns of 10 patients with left- versus right-sided dominant symptoms. Five
      healthy controls were also investigated with the same settings. METHODS: We
      grouped patients according to the predominant side of symptoms; thus, a right
      sided dominant and a left-sided dominant group was formed. The paradigm consisted
      of a 4-finger passive movement task, which altered with resting states. For each
      subject, this examination was performed twice: on the left and on the right hand
      separately. RESULTS: In healthy controls, motor-related areas contralateral to
      the moving fingers showed activation on fMRI. Concerning PD patients, motor
      related areas of the ipsilateral hemisphere - including the primary motor cortex,
      supplementary motor area, and basal ganglia - seemed to be involved in the motor
      reorganization in PD. However, we could only demonstrate this reorganization in
      patients with right-sided dominant symptoms. CONCLUSIONS: We suggest that the
      human brain in PD tries to compensate for the failure of the basal ganglia motor
      loop by employing alternative (ipsilateral) motor pathways, indicating that a
      complex reorganization can also take place in disorders like PD which affect the
      whole motor-related network.

PMID- 21952073
TI  - Association between Helicobacter pylori infection and laryngeal squamous cell
      carcinoma in a Chinese male population.
AB  - OBJECTIVES: To investigate the presence of Helicobacter pylori in the larynx, and
      to identify the relationship between H. pylori infection and laryngeal squamous
      cell carcinoma in a male population. METHODS: This study included 59 male
      patients with laryngeal squamous cell carcinoma and 41 control subjects. Nested
      polymerase chain reaction and target fragment sequencing were used to detect the
      presence of H. pylori in laryngeal mucosa. Logistic regression analysis was used
      to assess the association between H. pylori infection and laryngeal cancer.
      RESULTS: H. pylori was present in a significantly greater number of patients with
      laryngeal carcinoma (76.3%) than in control subjects (31.7%) (p < 0.001). The
      correlation between H. pylori infection and laryngeal cancer was highly
      significant (OR = 9.82, 95% CI [3.35, 28.80], p < 0.001). CONCLUSIONS: The
      present study shows that H. pylori is present in the laryngeal mucosa of men, and
      supports a possible relationship between H. pylori infection and laryngeal
      squamous cell carcinoma in a male population.

PMID- 21952072
TI  - Generation of tumor-initiating cells by exogenous delivery of OCT4 transcription
      factor.
AB  - INTRODUCTION: Tumor-initiating cells (TIC) are being extensively studied for
      their role in tumor etiology, maintenance and resistance to treatment. The
      isolation of TICs has been limited by the scarcity of this population in the
      tissue of origin and because the molecular signatures that characterize these
      cells are not well understood. Herein, we describe the generation of TIC-like
      cell lines by ectopic expression of the OCT4 transcription factor (TF) in primary
      breast cell preparations. METHODS: OCT4 cDNA was over-expressed in four different
      primary human mammary epithelial (HMEC) breast cell preparations from reduction
      mammoplasty donors. OCT4-transduced breast cells (OTBCs) generated colonies
      (frequency ~0.01%) in self-renewal conditions (feeder cultures in human embryonic
      stem cell media). Differentiation assays, immunofluorescence,
      immunohistochemistry, and flow cytometry were performed to investigate the cell
      of origin of OTBCs. Serial dilutions of OTBCs were injected in nude mice to
      address their tumorigenic capabilities. Gene expression microarrays were
      performed in OTBCs, and the role of downstream targets of OCT4 in maintaining
      self-renewal was investigated by knock-down experiments. RESULTS: OTBCs overcame
      senescence, overexpressed telomerase, and down-regulated p16INK4A. In
      differentiation conditions, OTBCs generated populations of both myoepithelial and
      luminal cells at low frequency, suggesting that the cell of origin of some OTBCs
      was a bi-potent stem cell. Injection of OTBCs in nude mice generated poorly
      differentiated breast carcinomas with colonization capabilities. Gene expression
      microarrays of OTBC lines revealed a gene signature that was over-represented in
      the claudin-low molecular subtype of breast cancer. Lastly, siRNA-mediated
      knockdown of OCT4 or downstream embryonic targets of OCT4, such as NANOG and
      ZIC1, suppressed the ability of OTBCs to self-renew. CONCLUSIONS: Transduction of
      OCT4 in normal breast preparations led to the generation of cell lines possessing
      tumor-initiating and colonization capabilities. These cells developed high-grade,
      poorly differentiated breast carcinomas in nude mice. Genome-wide analysis of
      OTBCs outlined an embryonic TF circuitry that could be operative in TICs,
      resulting in up-regulation of oncogenes and loss of tumor suppressive functions.
      These OTBCs represent a patient-specific model system for the discovery of novel
      oncogenic targets in claudin-low tumors.

PMID- 21952074
TI  - Electrochemical DNA sensor by the assembly of graphene and DNA-conjugated gold
      nanoparticles with silver enhancement strategy.
AB  - Sensitive and selective detection of DNA is in urgent need due to its important
      role in human bodies. Many disorders, such as Alzheimer's disease and various
      cancers, are closely related with DNA damage. In this work, a novel
      electrochemical DNA biosensor was constructed on a DNA-assembling graphene
      platform which provided a robust, simple and biocompatible platform with large
      surface area for DNA immobilization. The as-designed DNA sensor was fabricated by
      directly assembling captured ssDNA on a graphene-modified electrode through the
      pi-pi stacking interaction between graphene and ssDNA bases. Then, the target DNA
      sequence and oligonucleotide probes-labeled AuNPs were able to hybridize in a
      sandwich assay format, following the AuNPs-catalyzed silver deposition. The
      deposited silver was further detected by differential pulse voltammetry. Owing to
      the high DNA loading ability of graphene and the distinct signal amplification by
      AuNPs-catalyzed silver staining, the resulting biosensor exhibited a good
      analytical performance with a wide detection linear range from 200 pM to 500 nM,
      and a low detection limit of 72 pM. Additionally, the biosensor was proved to be
      able to discriminate the complementary sequence from the single-base mismatch
      sequence. The simple biosensor is promising in developing electronic, on-chip
      assays in clinical diagnosis, environmental control, and drug discovery.

PMID- 21952079
TI  - Graphene oxide induced growth of one-dimensional fusiform zirconia nanostructures
      for highly selective capture of phosphopeptides.
AB  - Graphene oxide (GO) has been demonstrated as a nanostructure growth-directing
      template for the synthesis of fusiform zirconia nanostructures on GO planes. The
      obtained fusiform zirconia-GO hybrid composites (FZGO) have good dispersion
      ability and show highly selective capture of phosphopeptides from complex peptide
      mixtures.

PMID- 21952080
TI  - An artifacts removal post-processing for epiphyseal region-of-interest (EROI)
      localization in automated bone age assessment (BAA).
AB  - BACKGROUND: Segmentation is the most crucial part in the computer-aided bone age
      assessment. A well-known type of segmentation performed in the system is adaptive
      segmentation. While providing better result than global thresholding method, the
      adaptive segmentation produces a lot of unwanted noise that could affect the
      latter process of epiphysis extraction. METHODS: A proposed method with
      anisotropic diffusion as pre-processing and a novel Bounded Area Elimination
      (BAE) post-processing algorithm to improve the algorithm of ossification site
      localization technique are designed with the intent of improving the adaptive
      segmentation result and the region-of interest (ROI) localization accuracy.
      RESULTS: The results are then evaluated by quantitative analysis and qualitative
      analysis using texture feature evaluation. The result indicates that the image
      homogeneity after anisotropic diffusion has improved averagely on each age group
      for 17.59%. Results of experiments showed that the smoothness has been improved
      averagely 35% after BAE algorithm and the improvement of ROI localization has
      improved for averagely 8.19%. The MSSIM has improved averagely 10.49% after
      performing the BAE algorithm on the adaptive segmented hand radiograph.
      CONCLUSIONS: The result indicated that hand radiographs which have undergone
      anisotropic diffusion have greatly reduced the noise in the segmented image and
      the result as well indicated that the BAE algorithm proposed is capable of
      removing the artifacts generated in adaptive segmentation.

PMID- 21952081
TI  - Evidence for cAMP-independent bTREK-1 inhibition by ACTH and NPS-ACTH in
      adrenocortical cells.
AB  - Bovine adrenal zona fasciculata (AZF) cells express bTREK-1 K(+) channels that
      are inhibited by ACTH through cAMP-dependent pathways. In whole cell patch clamp
      recordings from AZF cells, we found that ACTH may also inhibit bTREK-1 by a cAMP
      independent mechanism. When the potent adenylyl cyclase (AC) antagonist 2,5
      dideoxyadenosine-3'-triphosphate (2,5-dd-3'-ATP) was applied intracellularly
      through the patch pipette, bTREK-1 inhibition by the AC activator forskolin was
      blocked. In contrast, bTREK-1 inhibition by ACTH was unaltered. The selective
      G(Salpha) antagonist NF449 also failed to blunt bTREK-1 inhibition by ACTH. At
      concentrations that produce little measurable increase in cAMP in bovine AZF
      cells, the O-nitrophenyl, sulfenyl-derivative of ACTH (NPS-ACTH) also inhibited
      bTREK-1 almost completely. Accordingly, 2,5-dd-3'-ATP at concentrations more than
      1000* its reported IC(50) did not block bTREK-1 inhibition by NPS-ACTH. These
      results indicate that ACTH and NPS-ACTH can inhibit native bTREK-1 K(+) channels
      in AZF cells by a mechanism that does not involve activation of AC.

PMID- 21952083
TI  - The role of miRNAs in progesterone action.
AB  - Small non-coding RNAs termed microRNAs (miRNAs) are mediators of post
      transcriptional gene silencing and are involved in all aspects of cell biology.
      Progesterone receptors (PR) are intimately involved in the normal physiology and
      diseases of hormone responsive tissues including the uterus and the breast.
      Recent evidence suggests that hormone regulated miRNAs play a substantial role in
      hormone receptor mediated gene regulation. However, relatively little is known
      regarding miRNAs regulated by PR or that target PR as compared to those regulated
      by or targeting estrogen receptors (ER). We summarize the state of current
      knowledge regarding miRNAs and PR action. We also delineate how progesterone
      regulated miRNAs might provide an additional level of control and fine tuning of
      gene regulation by hormone receptors and also facilitate cell- and tissue
      specific gene regulation PR.

PMID- 21952082
TI  - Progesterone receptors, their isoforms and progesterone regulated transcription.
AB  - This review discusses mechanisms by which progesterone receptors (PR) regulate
      transcription. We examine available data in different species and tissues
      regarding: (1) regulation of PR levels; and (2) expression profiling of progestin
      regulated genes by total PRs, or their PRA and PRB isoforms. (3) We address
      current views about the composition of progesterone response elements, and
      postulate that PR monomers acting through "half-site" elements are common,
      entailing cooperativity with neighboring DNA-bound transcription factors. (4) We
      summarize transcription data for multiple progestin-regulated promoters as
      directed by total PR, or PRA vs. PRB. We conclude that current models and methods
      used to study PR function are problematical, and recommend that future work
      employ cells and receptors appropriate to the species, focusing on analyses of
      the effects of endogenous receptors targeting endogenous genes in native
      chromatin.

PMID- 21952085
TI  - Exercise and IBS: no pain, no gain.

PMID- 21952084
TI  - Improved delivery of cardiovascular care (IDOCC) through outreach facilitation:
      study protocol and implementation details of a cluster randomized controlled
      trial in primary care.
AB  - BACKGROUND: There is a need to find innovative approaches for translating best
      practices for chronic disease care into daily primary care practice routines.
      Primary care plays a crucial role in the prevention and management of
      cardiovascular disease. There is, however, a substantive care gap, and many
      challenges exist in implementing evidence-based care. The Improved Delivery of
      Cardiovascular Care (IDOCC) project is a pragmatic trial designed to improve the
      delivery of evidence-based care for the prevention and management of
      cardiovascular disease in primary care practices using practice outreach
      facilitation. METHODS: The IDOCC project is a stepped-wedge cluster randomized
      control trial in which Practice Outreach Facilitators work with primary care
      practices to improve cardiovascular disease prevention and management for
      patients at highest risk. Primary care practices in a large health region in
      Eastern Ontario, Canada, were eligible to participate. The intervention consists
      of regular monthly meetings with the Practice Outreach Facilitator over a one- to
      two-year period. Starting with audit and feedback, consensus building, and goal
      setting, the practices are supported in changing practice behavior by
      incorporating chronic care model elements. These elements include (a) evidence
      based decision support for providers, (b) delivery system redesign for practices,
      (c) enhanced self-management support tools provided to practices to help them
      engage patients, and (d) increased community resource linkages for practices to
      enhance referral of patients. The primary outcome is a composite score measured
      at the level of the patient to represent each practice's adherence to evidence
      based guidelines for cardiovascular care. Qualitative analysis of the Practice
      Outreach Facilitators' written narratives of their ongoing practice interactions
      will be done. These textual analyses will add further insight into understanding
      critical factors impacting project implementation. DISCUSSION: This pragmatic,
      stepped-wedge randomized controlled trial with both quantitative and process
      evaluations demonstrates innovative methods of implementing large-scale quality
      improvement and evidence-based approaches to care delivery. This is the first
      Canadian study to examine the impact of a large-scale multifaceted cardiovascular
      quality-improvement program in primary care. It is anticipated that through the
      evaluation of IDOCC, we will demonstrate an effective, practical, and sustainable
      means of improving the cardiovascular health of patients across Canada. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT00574808.

PMID- 21952090
TI  - Study of brain plasticity ramps up in the 1970s: new phenomena and new
      explanations.

PMID- 21952087
TI  - A woman with a rare cause of ascites diagnosed on endoscopic ultrasonography.

PMID- 21952091
TI  - Do teleost fishes possess a homolog of mammalian isocortex?

PMID- 21952092
TI  - Sleep and wake in rhythmic versus arrhythmic chronotypes of a microphthalmic
      species of African mole rat (Fukomys mechowii).
AB  - The giant Zambian mole rat (Fukomys mechowii) is a subterranean Afrotropical
      rodent noted for its regressed visual system and unusual patterns of circadian
      rhythmicity--within this species some individuals exhibit distinct regular
      circadian patterns of locomotor activity while others have arrhythmic circadian
      patterns. The current study was aimed at understanding whether differences in
      circadian chronotypes in this species affect the patterns and proportions of the
      different phases of the sleep-wake cycle. Physiological parameters of sleep
      (electroencephalogram and electromyogram) and behaviour (video recording) were
      recorded continuously for 72 h from 6 mole rats (3 rhythmic and 3 arrhythmic)
      using a telemetric system and a low-light CCTV camera connected to a DVD
      recorder. The results indicate that the arrhythmic individuals spend more time in
      waking with a longer average duration of a waking episode, less time in non-rapid
      eye movement (NREM) with a shorter average duration of an NREM episode though a
      greater NREM sleep intensity, and similar sleep cycle lengths. The time spent in
      rapid eye movement (REM) and the average duration of an REM episode were similar
      between the chronotypes.

PMID- 21952094
TI  - Neutralizing antibodies to interferon beta-1b multiple sclerosis: a clinico
      radiographic paradox in the BEYOND trial.
AB  - BACKGROUND: The frequency and impact of neutralizing antibodies (NAbs) to
      interferon beta-1b (IFNbeta-1b) on clinical and radiographic outcomes is
      controversial. OBJECTIVE: To assess NAb impact in the BEYOND study. METHODS: 2244
      patients were randomized (2:2:1) to receive IFNbeta-1b, either 250 or 500 ug, or
      glatiramer acetate, 20 mg, and observed for 2-3.5 years. NAb titers were
      determined every 6 months. A titer >=20 NU/ml was considered NAb positive.
      Efficacy was compared between NAb-positive and NAb-negative patients, using
      comprehensive statistical analyses, taking into account the delayed appearance of
      NAbs, the time-dependent changes in the relapse rate, spontaneous reversions to
      NAb-negative status, NAb-titer level, and also adjusting for baseline factors.
      RESULTS: In the IFNbeta-1b 250 ug group, NAb-positive titers were detected (>=
      once) in 319 patients (37.0%); of these, 112 (35.1%) reverted to NAb-negative
      status. In the IFNbeta-1b 500 ug group, 340 patients (40.7%) became NAb-positive
      and 119 (35.0%) reverted to NAb-negative status. In both IFNbeta groups,
      especially the 250 ug arm, NAb-positive status was not associated with a
      convincing impact on any clinical outcome measure by any statistical analysis. By
      contrast, in both IFNbeta groups, NAbs were associated with a very consistent
      deleterious impact on most MRI outcomes. CONCLUSION: There was a notable
      dissociation between the impact of NAbs on MRI and clinical outcomes. On MRI
      measures, the impact was consistent and convincing, whereas on clinical measures
      a negative impact of NAbs was not found. The basis for this clinico-radiographic
      paradox is unknown but it suggests that the relationship between NAbs and the
      therapeutic effects of IFNbeta-1b is complex.

PMID- 21952095
TI  - The role of CD8(+) T cells in a model of multiple sclerosis induced with
      recombinant myelin oligodendrocyte glycoprotein.
AB  - BACKGROUND AND OBJECTIVES: Since CD8(+) T cells may be important in the
      pathogenesis of multiple sclerosis (MS), we examined their role in the DA rat
      experimental autoimmune encephalomyelitis (EAE) model induced by immunization
      with recombinant myelin oligodendrocyte glycoprotein (rMOG). METHODS: The
      inflammatory infiltrate in the spinal cord of affected animals was assessed by
      histology, electrophysiology and flow cytometry during the course of the disease
      (the first peak, remission and the second peak). The proportions of
      activated/memory effector (CD8(+)CD44(+)) and putative suppressor (CD8(+)CD28(-),
      CD8(+)CD25(high)) CD8(+) T cells in the draining lymph nodes were determined. To
      explore the role of CD8(+) T cells, similar experiments were performed in CD8(+)
      T cell depleted rats, before, during and after the first peak of the disease.
      RESULTS: Throughout the disease, both CD4(+) T cells and macrophages/activated
      microglia outnumbered CD8(+) T cells within the spinal cord. The number of
      putative suppressor CD8(+) T cells increased significantly both during and after
      the first peak suggesting the induction of a regulatory CD8(+) T-cell response.
      However, antibody-mediated depletion of CD8(+) T cells before induction of the
      disease, or after the first peak, did not significantly alter the incidence,
      severity or course of rMOG-induced EAE. CONCLUSIONS: The findings suggest that
      CD8(+) T cells do not play a significant role in the pathogenesis or regulation
      of EAE induced by rMOG in DA rats. In this respect, rMOG-induced EAE is not an
      appropriate model for studying the role of CD8(+) T cells in MS.

PMID- 21952096
TI  - Sunlight exposure and sun sensitivity associated with disability progression in
      multiple sclerosis.
AB  - BACKGROUND: Sunlight and vitamin D have been inversely associated with the risk
      of multiple sclerosis (MS). OBJECTIVE: We investigated sunlight exposure and sun
      sensitivity in relation to disability progression in MS. METHODS: We conducted a
      survey among persons with MS, registered by the Flemish MS society, Belgium, and
      stratified data according to relapsing-onset and progressive-onset MS. We used
      Kaplan-Meier survival and Cox proportional hazard regression analyses with time
      to Expanded Disability Status Scale (EDSS) 6 as outcome measure. Hazard ratios
      for the time from onset and from birth were calculated for the potentially
      predictive variables, adjusting for age at onset, gender and immunomodulatory
      treatment. RESULTS: 704 (51.3%) of the 1372 respondents had reached EDSS 6. In
      relapsing-onset MS, respondents reporting equal or higher levels of sun exposure
      than persons of the same age in the last 10 years had a decreased risk of
      reaching EDSS 6. In progressive-onset MS, increased sun sensitivity was
      associated with an increased hazard of reaching EDSS 6. CONCLUSION: The
      association of higher sun exposure with a better outcome in relapsing-onset MS
      may be explained by either a protective effect or reverse causality. Mechanisms
      underlying sun sensitivity might influence progression in progressive-onset MS.

PMID- 21952097
TI  - Temporal trends of disability progression in multiple sclerosis: findings from
      British Columbia, Canada (1975-2009).
AB  - BACKGROUND: Recent natural history studies suggest that multiple sclerosis (MS)
      is a more slowly progressing disease than previously thought. These observations
      are from studies separated by time, geography and methodological approach.
      OBJECTIVES: We investigated whether MS disease progression has changed over time
      in British Columbia, Canada. METHODS: The British Columbia MS database was
      queried for relapsing-onset MS patients with symptom onset from 1975 to <1995,
      first assessed within 15 years from onset and with at least two Expanded
      Disability Status Scale (EDSS) scores. Latest follow-up was to 2009. Patients
      were grouped by 5-year onset intervals (1975 to <1980, 1980 to <1985, 1985 to
      <1990, 1990 to <1995). Outcome was defined as time to reach sustained and
      confirmed EDSS 6 within 15 years of disease duration. Kaplan-Meier analysis was
      used to compare: the proportion of patients reaching EDSS 6 (primary analysis)
      and the time to EDSS 6 (secondary analysis) across the time-period groups.
      RESULTS: A total of 2236 relapsing-onset MS patients (73.4% female; mean age at
      onset: 32.3 +/- 8.8 years) were included. No significant temporal trend was found
      in the proportion of patients reaching EDSS 6 within 15 years from onset (28.5%,
      26.4%, 27.7%, 22.3% for intervals 1975 to <1980, 1980 to <1985, 1985 to <1990,
      1990 to <1995, respectively; p = 0.09) or in survival curves for time to reach
      the outcome (p = 0.14). CONCLUSIONS: Rates of disease progression remained
      relatively stable over two decades of MS onset in British Columbia, Canada. Our
      results suggest that differences in disease progression findings between natural
      history studies may be related to factors other than time period.

PMID- 21952098
TI  - Which walking capacity tests to use in multiple sclerosis? A multicentre study
      providing the basis for a core set.
AB  - BACKGROUND: Many different walking capacity test formats are being used. It is
      unclear whether walking speed, obtained from short tests, and walking distance,
      obtained from long tests, provide different clinical information. OBJECTIVES: To
      determine the differential effect of various short and long walk test formats on
      gait velocity, and the actual relationship between walking speed and walking
      distance in multiple sclerosis (MS) patients with diverse ambulation status.
      METHODS: A cross-sectional multicentre study design was applied. Ambulatory MS
      patients (Expanded Disability Status Scale (EDSS) 0-6.5; n = 189) were tested at
      11 sites. Short tests consisted of the Timed 25-Foot Walk (static start, fastest
      speed) and 10-Metre Walk Test (dynamic start, usual and fastest speed). Long
      tests consisted of the 2- and 6-Minute Walk Tests (fastest speed). Subjects were
      divided into mild (EDSS 0-4; n = 99) or moderate (EDSS 4.5-6.5; n = 79)
      disability subgroups. RESULTS: In both subgroups, the start protocol, instructed
      pace and length of test led to significantly different gait velocities. Fastest
      walking speed and 6-Minute walking distance showed the strongest correlation (R
      (2) = 0.78 in mild and R (2) = 0.81 in moderate MS; p < 0.01). Short tests'
      relative estimation errors for 6-Minute walking distance were 8-12% in mildly and
      15-16% in moderately affected subjects. Based on the 2-Minute Walk Test,
      estimation errors significantly reduced to approximately 5% in both subgroups.
      CONCLUSIONS: A single short test format at fastest speed accurately describes an
      MS patient's general walking capacity. For intervention studies, a long test is
      to be considered. We propose the Timed 25-Foot Walk and 2-Minute Walk Test as
      standards. Further research on responsiveness is needed.

PMID- 21952099
TI  - Abenquines A-D: aminoquinone derivatives produced by Streptomyces sp. strain
      DB634.
AB  - New bioactive secondary metabolites, called abenquines, were found in the
      fermentation broth of Streptomyces sp. strain DB634, which was isolated from the
      soils of the Chilean highland of the Atacama Desert. They are composed of an
      amino acid linked to an N-acetyl-aminobenzoquinone. Isolation of the abenquines
      (1-4), their structure elucidation by NMR analysis and MS, as well as the
      kinetics of their production are presented. The abenquines show inhibitory
      activity against bacteria, dermatophytic fungi and phosphodiesterase type 4b. The
      amino acid attached to the quinone is relevant to the enzyme inhibitory activity.

PMID- 21952100
TI  - Accelerometer measured level of physical activity indoors and outdoors during
      preschool time in Sweden and the United States.
AB  - BACKGROUND: It is important to understand the correlates of physical activity
      (PA) to influence policy and create environments that promote PA among preschool
      children. We compared preschoolers' PA in Swedish and in US settings and
      objectively examined differences boys' and girls' indoor and outdoor PA regarding
      different intensity levels and sedentary behavior. METHODS: Accelerometer
      determined PA in 50 children with mean age 52 months, (range 40-67) was recorded
      during preschool time for 5 consecutive weekdays at 4 sites. The children wore an
      Actigraph GTIM Monitor. RESULTS: Raleigh preschool children, opposite to Malmo
      preschoolers spent significantly more time indoors than outdoors (P<.001).
      Significantly more moderate-to-vigorous intensity physical activity (MVPA) was
      observed outdoors (P<.001) in both settings. Malmo children accumulated
      significantly more counts/min indoors (P<.001). The percent of MVPA during
      outdoor time did not differ between children at Raleigh and Malmo. CONCLUSION:
      Physical activity counts/minutes was significantly higher outdoors vs. indoors in
      both Malmo and Raleigh. Malmo preschoolers spent 47% of attendance time outdoors
      compared with 18% for Raleigh preschoolers which could have influenced the
      difference in preschool activity between the 2 countries. Time spent in MVPA at
      preschool was very limited and predominantly adopted outdoors.

PMID- 21952102
TI  - Discussion of preventive measures against the increase of suicide among males in
      Japan.

PMID- 21952101
TI  - Retinal complications after damaging the vitreolenticular barrier.
AB  - This article gives an overview of the vitreal anatomy and its changes in ageing,
      which have a significant impact on the two main retinal complications after
      damage of the vitreolenticular barrier, namely retinal detachment and cystoid
      macular edema. The possible reasons and pathomechanisms for this entity of
      retinal diseases in the context of anterior segment interaction are highlighted,
      and a summary of references is provided showing the epidemiology and consequences
      of such interventions.

PMID- 21952103
TI  - Does a sixth mechanism exist to explain lightning injuries?: investigating a
      possible new injury mechanism to determine the cause of injuries related to close
      lightning flashes.
AB  - Five mechanisms have been described in the literature regarding lightning injury
      mechanisms. A sixth mechanism is proposed in this article, namely, lightning
      barotrauma. A simple laboratory experiment was conducted using ordnance gelatin
      for ballistic studies. Lightning was simulated in a high-voltage laboratory using
      an 8/20-microsecond current impulse generator and discharged through ballistic
      gel. Temporary and permanent cavity formations were confirmed. The cavities
      formed were directly proportional to the currents used. Findings suggest that a
      sixth mechanism of lightning injury, namely, barotrauma, should be considered.

PMID- 21952106
TI  - Retractor with radial incision for scleral buckling.

PMID- 21952104
TI  - Vascular smooth muscle cell-derived adiponectin: a paracrine regulator of
      contractile phenotype.
AB  - Adiponectin is a cardioprotective adipokine derived predominantly from visceral
      fat. We recently demonstrated that exogenous adiponectin induces vascular smooth
      muscle cell (VSMC) differentiation via repression of mTORC1 and FoxO4. Here we
      report for the first time that VSMC express and secrete adiponectin, which acts
      in an autocrine and paracrine manner to regulate VSMC contractile phenotype.
      Adiponectin was found to be expressed in human coronary artery and mouse aortic
      VSMC. Importantly, siRNA knock-down of endogenous adiponectin in VSMC
      significantly reduced the expression of VSMC contractile proteins. Contractile
      protein deficiency was also observed in primary VSMC isolated from Adiponectin(-/
      ) mice. This deficiency could be rescued by culturing Adiponectin(-/-) VSMC in
      conditioned media from wild type (WT) VSMC. Moreover, the paracrine effect of
      VSMC-derived adiponectin was confirmed as adiponectin neutralizing antibody
      blocked the rescue. Overexpressed adiponectin also exerted paracrine effects on
      neighboring untransfected VSMC, which was also blocked by adiponectin
      neutralizing antibody. Interestingly, adiponectin expression was inducible by the
      PPARgamma agonist rosiglitazone. Our data support an important role for VSMC
      derived adiponectin in maintaining VSMC contractile phenotype, contributing to
      critical cardioprotective functions in the vascular wall. This article is part of
      a Special Issue entitled "Local Signaling in Myocytes".

PMID- 21952105
TI  - Detection of morphologic alterations by spectral-domain optical coherence
      tomography before and after half-dose verteporfin photodynamic therapy in chronic
      central serous chorioretinopathy.
AB  - PURPOSE: To study the morphologic features of serous retinal detachment, the
      photoreceptor inner and outer segment junction line, retinal pigment epithelium
      irregularities, pigment epithelial detachment, and the subfoveal choroid before
      and after treatment of chronic central serous chorioretinopathy, using spectral
      domain optical coherence tomography. METHODS: We studied 17 eyes of 17
      consecutive patients (all men) with chronic central serous chorioretinopathy. We
      performed photodynamic therapy (PDT) with half-dose (3 mg/m2) verteporfin. We
      studied morphologic features using spectral-domain optical coherence tomography
      before and at 1, 3, 6, and 12 months after PDT. RESULTS: Retinal detachment
      showed reattachment in 16 of the 17 eyes by 3 months after PDT. The inner and
      outer segment junction line could be visualized in 13 eyes at 6 months after PDT.
      Retinal pigment epithelium irregularities were confirmed in all 17 eyes before
      and during the year after PDT. Pigment epithelial detachment initially
      disappeared but then recurred in 5 eyes after PDT. Subfoveal highly reflective
      substances first lessened in intensity but then again became prominent in 2 eyes.
      CONCLUSION: The authors identified recurrent pigment epithelial detachment and/or
      retinal detachment during the 1-year period after PDT. Even if retinal detachment
      initially disappears, retinal pigment epithelium or choroidal morphologic changes
      can still develop. The effect of half-dose PDT for chronic central serous
      chorioretinopathy may thus be temporary.

PMID- 21952107
TI  - Formation and stability of oil-in-water nanoemulsions containing rice bran oil:
      in vitro and in vivo assessments.
AB  - BACKGROUND: Nanoemulsions have practical application in a multitude of commercial
      areas, such as the chemical, pharmaceutical and cosmetic industries. Cosmetic
      industries use rice bran oil in sunscreen formulations, anti ageing products and
      in treatments for skin diseases. The aim of this study was to create rice bran
      oil nanoemulsions using low energy emulsification methods and to evaluate their
      physical stability, irritation potential and moisturising activity on volunteers
      with normal and diseased skin types. RESULTS: The nanoemulsion developed by this
      phase diagram method was composed of 10% rice bran oil, 10% surfactants sorbitan
      oleate/PEG-30 castor oil, 0.05% antioxidant and 0.50% preservatives formulated in
      distilled water. The nanoemulsion was stable over the time course of this study.
      In vitro assays showed that this formulation has a low irritation potential, and
      when applied to human skin during in vivo studies, the nanoemulsion improved the
      skin's moisture and maintained normal skin pH values. CONCLUSION: The results of
      irritation potential studies and in vivo assessments indicate that this
      nanoemulsion has potential to be a useful tool to treat skin diseases, such as
      atopic dermatitis and psoriasis.

PMID- 21952108
TI  - Evaluation of traumatic optic neuropathy in patients with optic canal fracture
      using diffusion tensor magnetic resonance imaging: a preliminary report.
AB  - OBJECTIVE: To investigate the role of diffusion tensor magnetic resonance imaging
      (DT-MRI) in the evaluation of traumatic optic neuropathy (TON). METHODS: Six
      patients with TON underwent DT-MRI prior to decompression surgery. DTV 2 and
      Volume One 1.44 software were used to measure the fractional anisotropy (FA) and
      the mean apparent diffusion coefficient (ADC) of the optic nerves. White matter
      fiber bundle tracking was used to display optic nerves. RESULTS: Visual acuity
      was improved in 1 of the 6 patients after surgery. The mean FA of the injured eye
      declined significantly with regard to that of the normal eye (0.2438 +/- 0.0670
      vs. 0.4524 +/- 0.0531; t = 8. 711; p = 0. 000). The mean ADC on the injured side
      increased significantly compared with that on the normal side [(1.4172 +/-
      0.1208) * 10(-3) mm(2)/s vs. (1.0866 +/- 0.1179) * 10(-3) mm(2)/s; t = -5.316; p
      = 0. 003). The continuity of the intracanalicular segment of the optic nerve was
      interrupted in 3 patients without improved postoperative visual acuity. In 1
      patient with improved postoperative visual acuity, the fiber bundle of the optic
      nerve was somewhat less dense in the injured eye than in the normal eye.
      CONCLUSIONS: DT-MRI provides valuable information for evaluating the fibers of
      optic nerves in TON.

PMID- 21952109
TI  - Persistence of magnons in a site-diluted dimerized frustrated antiferromagnet.
AB  - We present inelastic neutron scattering and thermodynamic measurements
      characterizing the magnetic excitations in a disordered spin-liquid
      antiferromagnet with non-magnetic substitution. The parent compound
      Ba(3)Mn(2)O(8) is a dimerized, quasi-two-dimensional geometrically frustrated
      quantum disordered antiferromagnet. We substitute this compound with non-magnetic
      V(5+) for the S=1 Mn(5+) ions, Ba(3)(Mn(1-x)V (x))(2)O(8), and find that the
      singlet-triplet excitations which dominate the spectrum of the parent compound
      persist for the full range of substitution examined, up to x=0.3. We also observe
      additional low-energy magnetic fluctuations which are enhanced at the greatest
      substitution values.

PMID- 21952110
TI  - Mechanisms underlying potentiation of endothelin-1-induced myofilament Ca(2+)
      sensitization after subarachnoid hemorrhage.
AB  - Increased vascular smooth muscle contractility has an important role in the
      development of cerebral vasospasm after subarachnoid hemorrhage (SAH).
      Myofilament Ca(2+) sensitivity is a major determinant of smooth muscle
      contractility. We investigated changes in the Ca(2+)-sensitizing effect of
      endothelin-1 (ET-1) and the mechanisms underlying ET-1-induced Ca(2+)
      sensitization after SAH using a rabbit SAH model. After SAH, the contractile
      response to ET-1 was enhanced, and the ET(A) receptor expression was upregulated
      in the basilar artery. In alpha-toxin-permeabilized preparations, ET-1 induced
      enhanced and prolonged contraction after SAH, suggesting that ET-1-induced Ca(2+)
      sensitization is potentiated after SAH. Endothelin-1-induced Ca(2+) sensitization
      became less sensitive to inhibitors of Rho-associated coiled-coil protein kinase
      (ROCK) and protein kinase C (PKC) after SAH. The expression of PKCalpha, ROCK2,
      PKC-potentiated phosphatase inhibitor of 17 kDa (CPI-17) and myosin phosphatase
      target subunit 1 (MYPT1) was upregulated, and the level of phosphorylation of CPI
      17 and MYPT1 was elevated after SAH. This study demonstrated for the first time
      that the Ca(2+)-sensitizing effect of ET-1 on myofilaments is potentiated after
      SAH. The increased expression and activity of PKCalpha, ROCK2, CPI-17, and MYPT1,
      as well as the upregulation of ET(A) receptor expression are suggested to
      underlie the enhanced and prolonged Ca(2+) sensitization induced by ET-1.

PMID- 21952112
TI  - Ancient diversity of splicing motifs and protein surfaces in the wild emmer wheat
      (Triticum dicoccoides) LR10 coiled coil (CC) and leucine-rich repeat (LRR)
      domains.
AB  - In this study, we explore the diversity and its distribution along the wheat leaf
      rust resistance protein LR10 three-dimensional structure. Lr10 is a leaf rust
      resistance gene encoding a coiled coil-nucleotide-binding site-leucine-rich
      repeat (CC-NBS-LRR) class of protein. Lr10 was cloned and sequenced from 58
      accessions representing diverse habitats of wild emmer wheat in Israel.
      Nucleotide diversity was very high relative to other wild emmer wheat genes (pi=
      0.029). The CC domain was found to be the most diverse domain and subject to
      positive selection. Superimposition of the diversity on the CC three-dimensional
      structure showed that some of the variable and positively selected residues were
      solvent exposed and may interact with other proteins. The LRR domain was
      relatively conserved, but showed a hotspot of amino acid variation between two
      haplotypes in the ninth repeat. This repeat was longer than the other LRRs, and
      three-dimensional modelling suggested that an extensive alpha helix structure was
      formed in this region. The two haplotypes also differed in splicing regulation
      motifs. In genotypes with one haplotype, an intron was alternatively spliced in
      this region, whereas, in genotypes with the other haplotype, this intron did not
      splice at all. The two haplotypes are proposed to be ancient and maintained by
      balancing selection.

PMID- 21952111
TI  - PDGFR-beta as a positive regulator of tissue repair in a mouse model of focal
      cerebral ischemia.
AB  - Although platelet-derived growth factors (PDGFs) and receptors (PDGFRs) are
      abundantly expressed in the central nervous system, their functions largely
      remain elusive. We investigated the role of PDGFR-beta in tissue responses and
      functional recovery after photothrombolic middle cerebral artery occlusion
      (MCAO). In the normal adult mouse brain, PDGFR-beta was mainly localized in
      neurons and in pericyte/vascular smooth muscle cells (PC/vSMCs). From 3 to 28
      days after MCAO, postnatally induced systemic PDGFR-beta knockout mice (Esr-KO)
      exhibited the delayed recovery of body weight and behavior, and larger infarction
      volume than controls. In Esr-KO, PC/vSMC coverage was decreased and vascular
      leakage of infused fluorescent-labeled albumin was extensive within the ischemic
      lesion, but not in the uninjured cerebral cortex. Angiogenesis levels were
      comparable between Esr-KO and controls. In another PDGFR-beta conditional KO
      mouse (Nestin-KO), PDGFR-beta was deleted in neurons and astrocytes from
      embryonic day 10.5, but was preserved in PC/vSMCs. After MCAO, vascular leakage
      and infarction volume in Nestin-KO were worse than controls, but partly improved
      compared with Esr-KO. Astroglial scar formation in both Esr-KO and Nestin-KO was
      similarly reduced compared with controls after MCAO. These data suggested that
      PDGFR-beta signaling is crucial for neuroprotection, endogenous tissue repair,
      and functional recovery after stroke by targeting neurons, PC/vSMCs, and
      astrocytes.

PMID- 21952113
TI  - Interaction of the retinoic acid signaling pathway with spicule formation in the
      marine sponge Suberites domuncula through activation of bone morphogenetic
      protein-1.
AB  - BACKGROUND: The formation of the spicules in siliceous sponges involves the
      formation of cylinder-like structures in the extraspicular space, composed of the
      enzyme silicatein and the calcium-dependent lectin. SCOPE OF REVIEW: Molecular
      cloning of the cDNAs (carotene dioxygenase, retinal dehydrogenase, and BMB-1
      [bone morphogenic protein-1]) from the demosponge Suberites domuncula was
      performed. These tools were used to understand the retinoid metabolism in the
      animal by qRT-PCR, immunoblotting and TEM. MAJOR CONCLUSIONS: We demonstrate that
      silintaphin-2, a silicatein-interacting protein, is processed from a longer-sized
      15-kDa precursor to a truncated, shorter-sized 13kDa calcium-binding protein via
      proteolytic cleavage at the dipeptide Ala?Asp, mediated by BMP-1. The expression
      of this protease as well as the expression of two key enzymes of the carotinoid
      metabolism, the beta,beta-carotene-15,15'-dioxygenase and the retinal
      dehydrogenase/reductase, were found to be strongly up-regulated by retinoic acid.
      Hence retinoic acid turned out to be a key factor in skeletogenesis in the most
      ancient still existing metazoans, the sponges. GENERAL SIGNIFICANCE: It is shown
      that retinoic acid regulates the formation of the organic cylinder that surrounds
      the axis of the spicules and enables, as a scaffold, the radial apposition of new
      silica layers and hence the growth of the spicules.

PMID- 21952114
TI  - 'Cognitive' sinking skin flap syndrome.

PMID- 21952115
TI  - Graphdiyne: a versatile nanomaterial for electronics and hydrogen purification.
AB  - We theoretically extend the applications of graphdiyne, an experimentally
      available one-atom-thin carbon allotrope, to nanoelectronics and superior
      separation membrane for hydrogen purification on a precise level.

PMID- 21952116
TI  - Ab initio calculation of the MgO(100) interaction with He and Ne: a HF + MP2 and
      HF + MP2(B3LYP) comparison.
AB  - Second order Rayleigh Schrodinger perturbation theory is applied to calculate the
      correlation energy contribution to the London dispersion interaction to
      approximate the interaction of the He and Ne with the MgO(100) surface; single
      particle orbitals using either Hartree-Fock theory or hybrid-exchange density
      functional theory are used as the reference state.

PMID- 21952117
TI  - Associations between physical activity and overweight among U.S. youth by
      immigrant generation: results from the 2007 National Survey of Children's Health.
AB  - BACKGROUND: This study examines relations between parent and youth physical
      activity (PA; days per week), sports participation, and overweight (BMI>=85th
      percentile) among U.S. youth, and whether this relationship varies by immigrant
      generation and sex. METHODS: Participants included 28,691 youth ages 10-17 years
      from the 2007 National Survey of Children's Health. Youth were grouped into
      first, second, and third or higher generation. Primary analyses include Chi
      square and post hoc tests to assess mean differences, and adjusted logistic
      regressions to test associations between weight status and independent variables.
      RESULTS: Each additional day youth participated in PA decreased their odds of
      overweight (OW) by 10% [OR: 0.90 (0.87-0.94)]; participation in sports
      significantly reduced their odds of OW by 17% [OR: 0.83 (0.71-0.98)]. First
      generation boys who participated in sports had 70% lower odds of OW [OR: 0.30
      (0.11-0.83)] compared with first generation boys who did not participate in
      sports. For third generation girls, participation in sports reduced the odds of
      OW by 23% [OR: 0.77 (0.62-0.96)] compared with those who did not participate in
      sports. CONCLUSION: The protective influence of PA on youth's risk of OW varies
      by immigrant generation and sex. Parent PA was not related to youth's risk of OW.

PMID- 21952118
TI  - The solid-state organization of 'self-doped' PPV oligomers.
AB  - Using a combination of multi-frequency EPR and NMR spectroscopy and quantum
      chemical calculations at the level of Density Functional Theory (DFT), the
      organization of self-doped PPV oligomers in their solid state is investigated.
      The analysis of the different spectra shows that the electrochemical procedure
      used to self-dope these materials produces positive radicals (polarons) in an
      almost quantitative way, but still magnetically isolated polarons are observed.
      The difference between chemical and electrochemical oxidation of the oligomers is
      studied in detail. Furthermore, ageing of the electrochemically oxidized
      oligomers may be accompanied by a stacking of the oligomers.

PMID- 21952119
TI  - Enzyme-linked immunosorbent assay gliadin assessment in processed food products
      available for persons with celiac disease: a feasibility study for developing a
      gluten-free food database.
AB  - Inappropriate food labeling and unwillingness of food companies to officially
      register their own gluten-free products in the Greek National Food Intolerance
      Database (NFID) result in a limited range of processed food products available
      for persons with celiac disease (CDP). The objective of the study was to evaluate
      the feasibility of developing a gluten-free food product database based on the
      assessment of the gluten content in processed foods available for CDP. Gluten was
      assessed in 41 processed food products available for CDP. Group A consisted of 26
      products for CDP included in the NFID, and group B contained 15 food products for
      CDP not registered in the NFID but listed in the safe lists of the local Celiac
      Association (CA). High-sensitivity omega-gliadin enzyme-linked immunosorbent
      assay (ELISA) was used for analysis. Gluten was lower than 20 ppm in 37 of 41
      analyzed products (90.2%): in 24 of 26 (92.3%) products in group A and in 13 of
      15 (86.7%) products in group B (P = .61). No significant difference was found
      between the 2 groups regarding gluten content. No product in either group
      contained gluten in excess of 100 ppm. Most of the analyzed products included in
      the Greek NFID or listed in the lists of the local CA, even those not officially
      labeled "gluten free," can be safely consumed by CDP. The use of commercially
      available omega-gliadin ELISA is able to identify those products that contain
      inappropriate levels of gluten, making feasible it to develop an integrated
      gluten-free processed food database.

PMID- 21952120
TI  - The red cell distribution width: what is its value for risk prognostication and
      for understanding disease pathophysiology?

PMID- 21952121
TI  - Correlation between reentrant spin glass behavior and the magnetic order-disorder
      transition of the martensite phase in Ni-Co-Mn-Sb Heusler alloys.
AB  - We have performed ac susceptibility and dc magnetization measurements in Ni(50
      x)Co(x)Mn(38)Sb(12) Heusler alloys. From the ac susceptibility measurements, the
      existence of reentrant spin glass (RSG) state is observed for x=0-5. It is found
      that the signature of RSG behavior diminishes with increase in x. This behavior
      is in contrast to the fact that the exchange bias field increases with x, which
      reveals that the origins of RSG and exchange bias are different in the present
      system. It is found that the system enters a frustrated ferromagnetic state just
      below the Curie temperature of the martensite phase (T(M)(C)) and then the RSG
      state at low temperature. The strength of the RSG state is critically dependent
      on the sharpness of the magnetic transition at (T(M)(C)). This proposition is
      further supported by the thermo-remanent magnetization and low field
      thermomagnetic measurements.

PMID- 21952123
TI  - Good news and bad news:  depressive symptoms decline and undertreatment increases
      with age in home care and institutional settings.
AB  - OBJECTIVES: Examination of prevalence of depressive symptoms among older persons
      in home care (HC) and complex continuing care (CCC) hospitals/units, factors
      associated with depressive symptoms in those settings, and rate of antidepressant
      use among older persons with depressive symptoms. DESIGN: Observational study
      using data from interRAI assessments used in normal clinical practice. Logistic
      regression models were used to identify factors associated with depressive
      symptoms in the frail elderly and treatment approaches were described. SETTINGS:
      Fourteen HC agencies and 134 CCC hospitals/units in Ontario, Canada.
      PARTICIPANTS: Older persons (N = 191,9871) aged 65 years and older, including
      114,497 persons from HC and 77,490 persons from CCC. MEASUREMENT: Data were
      collected using Resident Assessment Instrument 2.0 (RAI 2.0) (1996-2004) in CCC
      and Resident Assessment Instrument for Home Care (RAI-HC) (2003-2004) in HC.
      RESULTS: Prevalence of depressive symptoms among older HC enrollees was lower
      (12.0%) than in CCC (23.6%). It decreased significantly with age in HC (to about
      6% in those older than 95 years) but there were not substantial age differences
      in CCC. Common factors associated with depressive symptoms in both types of care
      were cognitive impairment, instability of health, daily pain, disability in
      activities of daily living; however, advanced age lost its protective effect in
      CCC. Less than half of the persons in HC and CCC with depressive symptoms were
      treated with antidepressants and their use decreased with age. CONCLUSIONS:
      Undertreatment of depressive symptoms among older persons remains a serious
      problem. Learning more about factors associated with depressive symptoms among
      the oldest old might improve detection and treatment of depression.

PMID- 21952122
TI  - The relationship of preparation for future care to depression and anxiety in
      older primary care patients at 2-year follow-up.
AB  - BACKGROUND: : Preparation for future care needs has been hypothesized to help
      older adults adjust to inevitable life and health transitions and thereby
      decrease the likelihood of developing depression or anxiety. METHODS: : A total
      of 190 primary care patients aged 65 years or more completed semistructured
      research interviews and mail-back surveys at study intake and 2 years later.
      Interviews included the Structured Clinical Interview for Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition, the Hamilton Depression
      Rating Scale, Clinical Anxiety Scale and a measure of preparation for future
      care. Multiple regression analyses were used to determine the independent
      association of preparation for future care at intake with depression and anxiety
      severity at 2-year follow-up. RESULTS: : Patients who had made more concrete
      plans at intake were less likely to meet criteria for depression diagnosis at
      follow-up. They also had lower anxiety severity scores. Patients who had avoided
      thinking about future care needs had greater depression symptom severity at
      follow-up. Findings were independent of potential confounds, including illness
      burden. CONCLUSIONS: : Failure to prepare for future care is a novel putative
      risk marker for depression and anxiety in older adulthood. Clinicians should be
      aware that the lack of care planning and frank avoidance may pose a risk for
      depression and anxiety older their patients. Future research should explore the
      mechanisms of care planning's effects on subsequent mood.

PMID- 21952124
TI  - Microwave assisted synthesis and magnetic properties of octanuclear and
      enneanuclear Ni(II) complexes: an unprecedented coordination mode for the NO(2)(
      ) ligand.
AB  - Octanuclear and enneanuclear Ni(II) complexes have been synthesized using a
      microwave reactor. The octanuclear complex Ni(8) presents a new triply bridging
      coordination mode for the NO(2)(-) ligand.

PMID- 21952125
TI  - Aerobic oxidation of alcohols over hydrotalcite-supported gold nanoparticles: the
      promotional effect of transition metal cations.
AB  - Chromium (III)-containing hydrotalcites show strong synergy with gold
      nanoparticles in achieving high activity in the aerobic oxidation of alcohols.

PMID- 21952126
TI  - Sultone opening with [18F]fluoride: an efficient 18F-labelling strategy for PET
      imaging.
AB  - Sultones were subject to ring opening by nucleophilic attack with [(18)F]fluoride
      to afford easily purified (18)F-labelled hydrophilic sulfonated products in high
      yields. A two-step sequence including radiofluorination and coupling to lysine
      was then developed from a bis-sultone precursor as a model approach for the
      labelling of biopolymers.

PMID- 21952128
TI  - D184E mutation in aquaporin-4 gene impairs water permeability and links to
      deafness.
AB  - Aquaporins (AQPs) play a physiological role in several organs and tissues, and
      their alteration is associated with disorders of water regulation. The
      identification of molecular interactions, which are crucial in determining the
      rate of water flux through the channel, is of pivotal role for the discovery of
      molecules able to target those interactions and therefore to be used for
      pathologies ascribable to an altered AQP-dependent water balance. In the present
      study, a mutational screening of human aquaporin-4 (AQP4) gene was performed on
      subjects with variable degrees of hearing loss. One heterozygous missense
      mutation was identified in a Spanish sporadic case, leading to an Asp/Glu amino
      acid substitution at position 184 (D184E). A BLAST analysis revealed that the
      amino acid D184 is conserved across species, consistently with a crucial role in
      the structure/function of AQP4 water channels. The mutation induces a significant
      reduction in water permeability as measured by the Xenopus laevis oocytes
      swelling assay and by the use of mammalian cells by total internal reflection
      microscopy. By Western blot, immunofluorescence and 2D Blue Native/SDS-PAGE we
      show that the reduction in water permeability is not ascribable to a reduced
      expression of AQP4 mutant protein or to its incorrect plasma membrane targeting
      and aggregation into orthogonal arrays of particles. Molecular dynamics
      simulation provided a molecular explanation of the mechanism whereby the mutation
      induces a loss of function of the channel. Substituting glutamate for aspartate
      affects the mobility of the D loop, which acquires a higher propensity to
      equilibrate in a "closed conformation", thus affecting the rate of water flux. We
      speculate that this mutation, combined with other genetic defects or concurrently
      with certain environmental stimuli, could confer a higher susceptibility to
      deafness.

PMID- 21952129
TI  - Compulsivity predicts fronto striatal activation in severely anorectic
      individuals.
AB  - Anorexia nervosa is a severe illness and shows one of the highest death rates
      among psychiatric or psychosomatic diseases. However, despite several lines of
      research, the etiology of this disease is still unknown. One of those features is
      the rigidity of behaviors, for example, controlling of weight and pursuing of
      thinness, that often meets the criteria for obsessive-compulsive behavior. In
      this study, it was investigated whether the clinical feature of compulsivity in
      anorexia nervosa patients relates to regional brain activation. Using functional
      magnetic resonance imaging, 12 severely anorectic women were compared to 12
      normal-weight female individuals following a cue-reactivity paradigm. Cues
      comprised food cues of high and low calorie content as well as eating-related
      utensils. Voxel-based morphometric analysis indicated significantly overall
      reduced gray matter volume and significantly increased cerebrospinal fluids in
      anorexia nervosa (AN) patients, which was controlled for in subsequent analyses.
      Following the high-calorie stimulation, AN patients activated the right caudate
      body and right precuneus, whereas control subjects did not show significant
      regional activations. In both other conditions, low-calorie foods and eating
      utensils, regional brain activations did not survive FDR thresholds. During the
      high-calorie condition, compulsivity, that is, the subscore "obsessive thoughts,"
      predicted activation of the superior frontal gyrus [Brodmann areas (BA) 10],
      inferior frontal gyrus, anterior cingulate cortex (BA 32), cingulate gyrus (BA
      24), caudate body, cuneus, pre- and postcentral gyrus. The subscore "compulsive
      acts" correlated with activation of the claustrum during the high-calorie
      condition and predicted a number of deactivations of frontal and temporal
      regions. We conclude that in severely anorectic individuals, the degree of
      compulsivity predicts activation and deactivation of the fronto-striatal pathway.

PMID- 21952130
TI  - Electrophysiological characteristics of inhibitory neurons of the prepositus
      hypoglossi nucleus as analyzed in Venus-expressing transgenic rats.
AB  - The identification and characterization of excitatory and inhibitory neurons are
      significant steps in understanding neural network functions. In this study, we
      investigated the intrinsic electrophysiological properties of neurons in the
      prepositus hypoglossi nucleus (PHN), a brainstem structure that is involved in
      gaze holding, using whole-cell recordings in brainstem slices from vesicular GABA
      transporter (VGAT)-Venus transgenic rats, in which inhibitory neurons express the
      fluorescent protein Venus. To characterize the intrinsic properties of these
      neurons, we recorded afterhyperpolarization (AHP) profiles and firing patterns
      from Venus-expressing [Venus+] and Venus-non-expressing [Venus-] PHN neurons.
      Although both types of neurons showed a wide variety of AHP profiles and firing
      patterns, oscillatory firing was specific to Venus+ neurons, while a firing
      pattern showing only a few spikes was specific to Venus- neurons. In addition,
      AHPs without a slow component and delayed spike generation were preferentially
      displayed by Venus+ neurons, whereas a firing pattern with constant interspike
      intervals was preferentially displayed by Venus- neurons. We evaluated the mRNAs
      expression of glutamate decarboxylase (GAD65, GAD67) and glycine transporter 2
      (GlyT2) to determine whether the recorded Venus+ neurons were GABAergic or
      glycinergic. Of the 67 Venus+ neurons tested, GlyT2 expression alone was detected
      in only one neuron. Approximately 40% (28/67) expressed GAD65 and/or GAD67
      (GABAergic neuron), and the remainder (38/67) expressed both GAD(s) and GlyT2
      (GABA&GLY neuron). These results suggest that most inhibitory PHN neurons use
      either GABA or both GABA and glycine as neurotransmitters. Although the overall
      distribution of firing patterns in GABAergic neurons was similar to that of
      GABA&GLY neurons, only GABA&GLY neurons exhibited a firing pattern with a long
      first interspike interval. These differential electrophysiological properties
      will be useful for the identification of specific types of PHN neurons.

PMID- 21952131
TI  - Pharmacological inhibition of endocannabinoid degradation modulates the
      expression of inflammatory mediators in the hypothalamus following an
      immunological stressor.
AB  - The endocannabinoid system is an important regulator of the nervous,
      neuroendocrine, and immune systems, thus representing a novel therapeutic target
      for stress-related neuroinflammatory and psychiatric disorders. However, there is
      a paucity of data relating to the effects of endocannabinoids on
      neuroinflammatory mediators following an immune stress/challenge in vivo. This
      study investigated the effects of URB597, a selective inhibitor of fatty acid
      amide hydrolyase (FAAH), the enzyme that preferentially metabolizes anandamide,
      on lipopolysaccharide (LPS)-induced increases in the expression of immune
      mediators in the hypothalamus. Systemic administration of URB597 increased the
      levels of anandamide and the related N-acylethanolamines, N
      palmitoylethanolamide, and N-oleoylethanolamide, but not 2-arachidonoyl glycerol,
      in the hypothalamus and spleen. URB597 attenuated the LPS-induced increase in
      interleukin (IL)-1beta expression while concurrently augmenting the LPS-induced
      increase in suppressor of cytokine signalling (SOCS)-3 expression. In addition,
      URB597 tended to enhance and reduce the LPS-induced increase in IL-6 and IL-10
      mRNA expression, respectively. LPS-induced increases in peripheral cytokine
      levels or plasma corticosterone were not altered by URB597. The present study
      provides evidence for a role for FAAH in the regulation of LPS-induced expression
      of inflammatory mediators in the hypothalamus. Improved understanding of
      endocannabinoid-mediated regulation of neuroimmune function has fundamental
      physiological and potential therapeutic significance in the context of stress
      related disorders.

PMID- 21952132
TI  - Restricted feeding regime affects clock gene expression profiles in the
      suprachiasmatic nucleus of rats exposed to constant light.
AB  - The master circadian clock located in the suprachiasmatic nuclei (SCN) is
      dominantly entrained by external light/dark cycle to run with a period of a solar
      day, that is, 24 h, and synchronizes various peripheral clocks located in the
      body's cells and tissues accordingly. A daily restricted normocaloric feeding
      regime synchronizes the peripheral clocks but has no effect on SCN rhythmicity.
      The aim of this study was to elucidate whether feeding regime may affect the
      molecular mechanism generating SCN rhythmicity under conditions in which the
      rhythmicity is disturbed, as occurs under constant light. The rats were
      maintained under constant light for 30 days and were either fed ad libitum during
      the whole period, or their access to food was restricted to only 6 h a day during
      the last 2 weeks in constant light. Locomotor activity was monitored during the
      whole experiment. On the last day in constant light, daily expression profiles of
      the clock genes Per1, Per2, Bmal1, and Rev-erbalpha were determined in the SCN of
      both groups by in situ hybridization. Due to their exposure to constant light,
      the rats fed ad libitum became completely arrhythmic, while those exposed to the
      restricted feeding were active mostly during the time of food availability. In
      the SCN of behaviorally arrhythmic rats, no oscillations in Rev-erbalpha and
      Bmal1 gene expression were detected, but very low amplitude, borderline
      significant, oscillations in Per1 and Per2 persisted. Restricted feeding induced
      significant circadian rhythms in Rev-erbalpha and Bmal1 gene expression, but did
      not affect the low amplitude oscillations of Per1 and Per2 expression. These
      findings demonstrate that, under specific conditions, when the rhythmicity of the
      SCN is disturbed and other temporal entraining cues are lacking, the SCN
      molecular clockwork may likely sense temporal signals from changes in metabolic
      state delivered by normocaloric food.

PMID- 21952133
TI  - Interactive and individual effects of sensory potentiation and region-specific
      changes in excitability after spinal cord injury.
AB  - While promoting regeneration across lesion sites is a main focus of research into
      spinal injury, changes also occur in the sublesion spinal cord and its sensory
      inputs. However, how these varied effects relate to recovery remains largely
      unknown. Here, we have examined changes in sensory inputs and region-specific
      changes in spinal cord excitability after spinal cord lesions in the lamprey, a
      model system for studying regeneration and functional recovery, and related the
      changes to the degree of locomotor recovery.Proprioceptive responses below lesion
      sites were potentiated and their rate of adaptation reduced 8-10 weeks after
      lesioning (i.e. when animals usually showed significant locomotor recovery).
      These effects were associated with changes in cellular properties that were
      consistent with an increase in proprioceptor excitability. However, the changes
      in proprioceptive inputs did not correlate with the degree of locomotor recovery.
      There were region-specific changes in spinal cord excitability below lesion
      sites. In isolation, these excitability changes also did not correlate with the
      degree of locomotor recovery, but in this case, there were significant
      interactions between the magnitude of stimulation-evoked responses across the
      lesion site (used to assess the extent of regeneration) and sublesion changes in
      excitability. These interactions differed in animals that recovered well or
      poorly, suggesting that the nature of this interaction influenced recovery. These
      results add to the evidence for diverse changes in the spinal cord after injury,
      and suggest that regenerated inputs and their interactions with sublesion
      networks influence the degree of functional recovery.

PMID- 21952134
TI  - A regression model approach to enable cell morphology correction in high
      throughput flow cytometry.
AB  - Cells exposed to stimuli exhibit a wide range of responses ensuring phenotypic
      variability across the population. Such single cell behavior is often examined by
      flow cytometry; however, gating procedures typically employed to select a small
      subpopulation of cells with similar morphological characteristics make it
      difficult, even impossible, to quantitatively compare cells across a large
      variety of experimental conditions because these conditions can lead to profound
      morphological variations. To overcome these limitations, we developed a
      regression approach to correct for variability in fluorescence intensity due to
      differences in cell size and granularity without discarding any of the cells,
      which gating ipso facto does. This approach enables quantitative studies of
      cellular heterogeneity and transcriptional noise in high-throughput experiments
      involving thousands of samples. We used this approach to analyze a library of
      yeast knockout strains and reveal genes required for the population to establish
      a bimodal response to oleic acid induction. We identify a group of epigenetic
      regulators and nucleoporins that, by maintaining an 'unresponsive population,'
      may provide the population with the advantage of diversified bet hedging.

PMID- 21952135
TI  - Arabidopsis G-protein interactome reveals connections to cell wall carbohydrates
      and morphogenesis.
AB  - The heterotrimeric G-protein complex is minimally composed of Galpha, Gbeta, and
      Ggamma subunits. In the classic scenario, the G-protein complex is the nexus in
      signaling from the plasma membrane, where the heterotrimeric G-protein associates
      with heptahelical G-protein-coupled receptors (GPCRs), to cytoplasmic target
      proteins called effectors. Although a number of effectors are known in metazoans
      and fungi, none of these are predicted to exist in their canonical forms in
      plants. To identify ab initio plant G-protein effectors and scaffold proteins, we
      screened a set of proteins from the G-protein complex using two-hybrid
      complementation in yeast. After deep and exhaustive interrogation, we detected
      544 interactions between 434 proteins, of which 68 highly interconnected proteins
      form the core G-protein interactome. Within this core, over half of the
      interactions comprising two-thirds of the nodes were retested and validated as
      genuine in planta. Co-expression analysis in combination with phenotyping of loss
      of-function mutations in a set of core interactome genes revealed a novel role
      for G-proteins in regulating cell wall modification.

PMID- 21952138
TI  - Interaction between a novel intronic IVS3+172 variant and N29I mutation in PRSS1
      gene is associated with pancreatitis in a Malaysian Chinese family.
AB  - BACKGROUND/AIMS: Hereditary pancreatitis (HP) is a very rare form of early-onset
      chronic pancreatitis, which usually begins in childhood with a variable spectrum
      of severity of disease. HP is commonly caused by variants/mutations in the PRSS1
      gene as reported in many studies. Therefore, in this study, we aimed to
      investigate the possible association of PRSS1 gene variants/mutations in a
      Malaysian Chinese family with HP. METHODS: Genomic DNA of the 6 family members
      was extracted, amplified using polymerase chain reaction and the entire PRSS1
      gene was analyzed via sequencing. RESULTS: PRSS1 gene sequencing results revealed
      two variants/mutations in this study. The results show that all the subjects
      (patients) inherited an intronic SNP IVS3+172 variant, together with a p.N29I
      mutation except for subjects 3 and 4 who are normal. CONCLUSION: We believe that
      interaction between the novel IVS3+172 intronic variant and p.N29I mutation in
      the PRSS1 gene is associated with HP in this Malaysian Chinese family.

PMID- 21952137
TI  - Transcriptional activity regulates alternative cleavage and polyadenylation.
AB  - Genes containing multiple pre-mRNA cleavage and polyadenylation sites, or polyA
      sites, express mRNA isoforms with variable 3' untranslated regions (UTRs). By
      systematic analysis of human and mouse transcriptomes, we found that short 3'UTR
      isoforms are relatively more abundant when genes are highly expressed whereas
      long 3'UTR isoforms are relatively more abundant when genes are lowly expressed.
      Reporter assays indicated that polyA site choice can be modulated by
      transcriptional activity through the gene promoter. Using global and reporter
      based nuclear run-on assays, we found that RNA polymerase II is more likely to
      pause at the polyA site of highly expressed genes than that of lowly expressed
      ones. Moreover, highly expressed genes tend to have a lower level of nucleosome
      but higher H3K4me3 and H3K36me3 levels at promoter-proximal polyA sites relative
      to distal ones. Taken together, our results indicate that polyA site usage is
      generally coupled to transcriptional activity, leading to regulation of
      alternative polyadenylation by transcription.

PMID- 21952136
TI  - The MHC I immunopeptidome conveys to the cell surface an integrative view of
      cellular regulation.
AB  - Self/non-self discrimination is a fundamental requirement of life. Endogenous
      peptides presented by major histocompatibility complex class I (MHC I) molecules
      represent the essence of self for CD8 T lymphocytes. These MHC I peptides (MIPs)
      are collectively referred to as the immunopeptidome. From a systems-level
      perspective, very little is known about the origin, composition and plasticity of
      the immunopeptidome. Here, we show that the immunopeptidome, and therefore the
      nature of the immune self, is plastic and moulded by cellular metabolic activity.
      By using a quantitative high-throughput mass spectrometry-based approach, we
      found that altering cellular metabolism via the inhibition of the mammalian
      target of rapamycin results in dynamic changes in the cell surface MIPs
      landscape. Moreover, we provide systems-level evidence that the immunopeptidome
      projects at the cell surface a representation of biochemical networks and
      metabolic events regulated at multiple levels inside the cell. Our findings open
      up new perspectives in systems immunology and predictive biology. Indeed,
      predicting variations in the immunopeptidome in response to cell-intrinsic and 
      extrinsic factors could be relevant to the rational design of immunotherapeutic
      interventions.

PMID- 21952139
TI  - Novel transcript variants of TRAIL show different activities in activation of NF
      kappaB and apoptosis.
AB  - AIMS: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has
      many transcript variants, but whether they possess distinct function is not
      completely known. In the present study, we compared the function of these TRAIL
      variants. MAIN METHODS: A bioinformatics analysis was performed to examine
      potential TRAIL variants. For the functional study, over-expression of TRAIL
      isoforms was used to examine their NF-kappaB inducing and apoptotic activities in
      both cancer and normal cells. Moreover, soluble TRAIL E4 variant protein was
      expressed and purified in prokaryotic cells, and was used for apoptotic assay.
      KEY FINDINGS: We cloned seven truncated TRAIL variants, designated as AK, E2, E3,
      E4, DA, BX424, and BX439. In comparison with the wild type TRAIL protein
      expressed from full-length RefSeq, over-expression of all these TRAIL variants
      activated NF-kappaB and its targeting genes in human cells at varying degrees.
      Some isoforms including BX424, DA and E4 even showed NF-kappaB, IL8, CCL4 and
      CCL20 promoter activating activity stronger than the wild type protein. All
      truncated variant proteins had no toxicity to normal human cells, similar to the
      wild type protein; however, they all failed to induce apoptosis in cancer cells
      that are sensitive to TRAIL. Recombinant soluble TRAIL E4 protein also failed to
      antagonize TRAIL-induced apoptosis in cancer cells. SIGNIFICANCE: Truncated TRAIL
      variant proteins lost apoptotic activity but retained or even enhanced the NF
      kappaB activating potentials, these results suggest that TRAIL variants may play
      roles in non-apoptotic cellular processes that are more important than we
      previously thought.

PMID- 21952140
TI  - Characteristics of utility cyclists in Queensland, Australia: an examination of
      the associations between individual, social, and environmental factors and
      utility cycling.
AB  - BACKGROUND: Initiatives to promote utility cycling in countries like Australia
      and the US, which have low rates of utility cycling, may be more effective if
      they first target recreational cyclists. This study aimed to describe patterns of
      utility cycling and examine its correlates, among cyclists in Queensland,
      Australia. METHODS: An online survey was administered to adult members of a state
      based cycling community and advocacy group (n=1813). The survey asked about
      demographic characteristics and cycling behavior, motivators and constraints.
      Utility cycling patterns were described, and logistic regression modeling was
      used to examine associations between utility cycling and other variables.
      RESULTS: Forty-seven percent of respondents reported utility cycling: most did so
      to commute (86%). Most journeys (83%) were >5 km. Being male, younger, employed
      full-time, or university-educated increased the likelihood of utility cycling
      (P<.05). Perceiving cycling to be a cheap or a convenient form of transport was
      associated with utility cycling (P<.05). CONCLUSIONS: The moderate rate of
      utility cycling among recreational cyclists highlights a potential to promote
      utility cycling among this group. To increase utility cycling, strategies should
      target female and older recreational cyclists and focus on making cycling a cheap
      and convenient mode of transport.

PMID- 21952143
TI  - Mutism and amnesia following high-voltage electrical injury: psychogenic
      symptomatology triggered by organic dysfunction?
AB  - BACKGROUND: Mutism and dense retrograde amnesia are found both in organic and
      dissociative contexts. Moreover, dissociative symptoms may be modulated by right
      prefrontal activity. A single case, M.R., developed left hemiparesis, mutism and
      retrograde amnesia after a high-voltage electric shock without evidence of
      lasting brain lesions. M.R. suddenly recovered from his mutism following a mild
      brain trauma 2 years later. METHODS: M.R.'s neuropsychological pattern and
      anatomoclinical correlations were studied through (i) language and memory
      assessment to characterize his deficits, (ii) functional neuroimaging during a
      standard language paradigm, and (iii) assessment of frontal and left insular
      connectivity through diffusion tractography imaging and transcranial magnetic
      stimulation. A control evaluation was repeated after recovery. FINDINGS: M.R.
      recovered from the left hemiparesis within 90 days of the accident, which
      indicated a transient right brain impairment. One year later, neurobehavioral,
      language and memory evaluations strongly suggested a dissociative component in
      the mutism and retrograde amnesia. Investigations (including MRI, fMRI, diffusion
      tensor imaging, EEG and r-TMS) were normal. Twenty-seven months after the
      electrical injury, M.R. had a very mild head injury which was followed by a rapid
      recovery of speech. However, the retrograde amnesia persisted. DISCUSSION: This
      case indicates an interaction of both organic and dissociative mechanisms in
      order to explain the patient's symptoms. The study also illustrates dissociation
      in the time course of the two different dissociative symptoms in the same
      patient.

PMID- 21952144
TI  - Oxidizing metal ions with graphene oxide: the in situ formation of magnetic
      nanoparticles on self-reduced graphene sheets for multifunctional applications.
AB  - Fe(2+) cations in FeCl(2) or FeSO(4) were oxidized by graphene oxide, leading to
      an in situ deposition of Fe(3)O(4) nanoparticles onto the self-reduced graphene
      oxide (rGO) sheets. The resultant Fe(3)O(4)/rGO sheets were demonstrated to
      possess interesting magnetic and electrochemical properties attractive for a
      large variety of potential applications.

PMID- 21952145
TI  - Clathrate hydrate formation after CO2-H2O vapour deposition.
AB  - We study vapour condensation of carbon dioxide and water at 77 K in a high-vacuum
      apparatus, transfer the sample to a piston-cylinder apparatus kept at 77 K and
      subsequently heat it at 20 MPa to 200 K. Samples are monitored by in situ
      volumetric experiments and after quench-recovery to 77 K and 1 bar by powder X
      ray diffraction. At 77 K a heterogeneous mixture of amorphous solid water (ASW)
      and crystalline carbon dioxide is produced, both by co-deposition and sequential
      deposition of CO(2) and H(2)O. This heterogeneous mixture transforms to a mixture
      of cubic structure I carbon dioxide clathrate and crystalline carbon dioxide in
      the temperature range 160-200 K at 20 MPa. However, no crystalline ice is
      detected. This is, to the best of our knowledge, the first report of CO(2)
      clathrate hydrate formation from co-deposits of ASW and CO(2). The presence of
      external CO(2) vapour pressure in the annealing stage is not necessary for
      clathrate formation. The solid-solid transformation is accompanied by a density
      increase. Desorption of crystalline CO(2) atop the ASW sample is inhibited by
      applying 20 MPa in a piston-cylinder apparatus, and ultimately the clathrate is
      stabilized inside layers of crystalline CO(2) rather than in cubic or hexagonal
      ice. The vapour pressure of carbon dioxide needed for clathrate hydrate formation
      is lower by a few orders of magnitude compared to other known routes of CO(2)
      clathrate formation. The route described here is, thus, of relevance for
      understanding formation of CO(2) clathrate hydrates in astrophysical
      environments.

PMID- 21952146
TI  - Facile eta5-eta3 hapticity interconversion in pentamethylcyclopentadienyl
      ruthenium(II) complexes containing a phenylmethallyl ("open indenyl") ligand.
AB  - The indenyl effect has been introduced to pentadienyl ("open cyclopentadienyl")
      chemistry by preparation of the phenylmethallyl ("open indenyl") ligand oInd(Me).
      The reaction of its potassium salt K(oInd(Me)) with [(eta(5)-C(5)Me(5))RuCl](4)
      afforded the sandwich complex [(eta(5)-C(5)Me(5))Ru(eta(5)-oInd(Me))] (1), which,
      upon treatment with PMe(3), CO, and 2,6-dimethylphenyl isocyanide (CN-o-Xy),
      easily underwent eta(5)-eta(3) hapticity interconversion and formed the complexes
      [(eta(5)-C(5)Me(5))Ru(eta(3)-oInd(Me))(L)] (2, L = PMe(3); 3, L = CO; 4, L = CN-o
      Xy). In these complexes, the eta(3)-bound phenylmethallyl ligand adopts an anti
      conformation with regard to the relative positions of the phenyl and methyl
      substituents. For the PMe(3) complex anti-2, slow conversion to the syn-isomer
      was observed, and this equilibrium reaction was monitored by NMR spectroscopy at
      50  degrees C to determine a first order rate constant of k(323 K) = 6.57 * 10(
      6) (+/- 0.02 * 10(-6)) s(-1) and an activation barrier of DeltaG degrees  = 26.8
      kcal mol(-1). DFT calculations afforded a stabilization of syn-2 and syn-3 by
      DeltaG(298) = -1.54 and -1.74 kcal mol(-1) over the respective anti-isomer.

PMID- 21952147
TI  - Pardon my asking: do we need eMinence-based bioethics?

PMID- 21952148
TI  - Ethical issues in videorecording patients lacking capacity to consent.
AB  - Videorecording of patients requires the utmost respect for the privacy and
      confidentiality of the patients. Consent should be requested from patients for
      all videorecording. When a mental disability or mental or physical illness
      prevents patients from giving their permission, agreement to recording from a
      legal representative or from a close relative or carer are necessary. Three
      documents on this subject issued in the United Kingdom, the United State of
      America and Italy are briefly summarized and discussed. The problem of consent
      for videorecording is addressed particularly in reference to persons incapable of
      making decisions on their own, such as persons in vegetative state. The general
      ethical framework is outlined and a few practical proposals are given.

PMID- 21952149
TI  - Awareness, understanding and attitudes of Italians regarding palliative care.
AB  - There are numerous difficulties encountered in the diffusion of palliative care
      (PC) in developed countries. A correct and widespread awareness of PC among the
      general public represents an important factor for its enhanced diffusion and use.
      The aim of this study is to verify the level of awareness of PC among Italians
      and their perception of the needs of patients with incurable illness. A random
      sample of 1897 adult subjects, aged 18 to 74 years, representative of the Italian
      population, was interviewed after stratification by gender, age (6 strata),
      education (3 levels), geographic area of residency (4 areas) and town of
      residency (4 dimensions). 59.4% of those interviewed had heard of PC, but only
      23.5% of them believed that they had an adequate or precise idea of what PC is;
      27% of them did not know or had a mistaken idea about the nature of PC. The most
      accepted perception was that PC alleviates pain and improves quality-of-life. The
      principal concerns attributed to incurable patients were: fear of suffering and
      of death, and the principal needs were perceived as: relief from pain and
      physical suffering. The primary needs of the family were identified in: medical
      and nursing care at home, followed by: care provided by volunteers and
      psychological support. The most appropriate care-setting for these patients was
      indicated as their home, possibly with the support of professional carers. In the
      case of children, the main concern indicated was that of being "separated" from
      family, friends, home and toys. Only 45.2% of interviewees thought that they knew
      a person who had experienced PC. In conclusion, the awareness of the Italian
      population of PC is scarce and often incorrect. In order to achieve a greater
      diffusion and better use of PC in our country, this awareness needs to be
      improved by appropriate intervention.

PMID- 21952150
TI  - Smoke-free policy development in Italy through the legislative process of the ban
      2000-2005, and press media review 1998-2008.
AB  - The objective of this article is to describe the process of approval of the
      Italian smoking ban, enacted in 2005. The method is to conduct a review of
      proposed and approved legislation 2000- 2005, and of articles published in
      Italian newspapers, 1998-2008. Enabling factors in the process were: the
      leadership of two consecutive Health Ministers, both physicians, who introduced
      the bill four times between 2000-2002; the repeated presentation and final
      approval of the bill as an amendment within a bill on public administration which
      enabled timely approval of the ban; and the stringent air quality standards in
      the 2003 regulation that made building smoking rooms impracticable and
      prohibitively expensive. Limiting factors in the process were: the 6-month delay
      in approving the regulation on smoking rooms; the 1.5-year delay in approving the
      regulation establishing owners' responsibility for enforcing the ban in
      hospitality premises and the legal action in August 2005, which shifted
      responsibility for enforcement to police. Eighty-three percent of the 808
      articles published on smoking in 1998-2008 were released between 2000-2005,
      during the policy process. While the press devoted considerable attention to the
      issues raised by the hospitality sector, the long legislative process of the bill
      and its regulations also stimulated coverage on tobacco control issues.

PMID- 21952151
TI  - Prevention, communication and equity in environmental epidemiology: ethical
      issues.
AB  - In environmental epidemiology research, decisions about when and how to intervene
      requires adequate ethical reflection. In fact, different kinds of issues may
      arise about: research methods and knowledge production; management of the results
      in terms of their overall assessments or for the implementation of preventive
      actions; reclamation intervention. In this contribution we propose to consider
      three topics we regard as crucial to this ethical debate: the reporting of
      conclusive research data; the correct application of the precautionary principle;
      and the environmental equity issues.

PMID- 21952152
TI  - Ethical issues in neonatal intensive care.
AB  - Recent progress in neonatal care have significantly improved the prognosis and
      chances of survival of critically ill or extremely preterm neonates and have
      modified the limits of viability. However, in some circumstances, when the
      child's death can only be briefly postponed at the price of severe suffering, or
      when survival is associated with severe disabilities and an intolerable life for
      the child and his/her parents, the application of the full armamentarium of
      modern neonatal intensive care may not be appropriate. In such circumstances the
      limitation of intensive treatments (withholding or withdrawing) and shift towards
      palliative care, can represent a more humane and reasonable alternative. This
      article examines and discusses the ethical principles underlying such difficult
      decisions, the most frequent situations in which these decisions may be
      considered, the role of parents in the decisional process, and the opinions and
      behaviours of neonatologists of several European neonatal intensive units as
      reported by the EURONIC study.

PMID- 21952153
TI  - Hypovolemic shock due to severe gastrointestinal bleeding in a child taking an
      herbal syrup.
AB  - We report the case of a 4-years-old boy who was admitted with hypovolemic shock
      due to a severe gastrointestinal bleeding. The esophagogastroduodenoscopy (EGDS)
      showed hiatus hernia, erosions and ulcerations of the lower esophagus, possibly
      due to a gastroesophageal reflux, and a small duodenal erosion. The child was
      previously healthy and he had never shown any symptoms related to this condition.
      The only product taken by the child in the previous days was a syrup containing
      several herbs, among which Filipendula ulmaria (L.) Maxim. and Salix spp. (known
      to contain salicylates), marketed as food and prescribed by his paediatrician to
      treat a mild cold accompanied by fever. Quali-quantitative analysis confirmed the
      presence of salicylates in the syrup. Naranjo algorithm showed a probable
      correlation between the onset of symptoms and the consumption of the herbal
      remedy. The child recovered after receiving intensive care. The product was
      withdrawn from Italian market.

PMID- 21952154
TI  - Effect of eye NGF administration on two animal models of retinal ganglion cells
      degeneration.
AB  - The aim of this study was to investigate the effect of nerve growth factor (NGF)
      administration on retinal ganglion cells (RGCs) in experimentally induced
      glaucoma (GL) and diabetic retinopathy (DR). GL was induced in adult rats by
      injection of hypertonic saline into the episcleral vein of the eye and diabetes
      (DT) was induced by administration of streptozoticin. Control and experimental
      rats were treated daily with either ocular application of NGF or vehicle
      solution. We found that both animal models present a progressive degeneration of
      RGCs and changing NGF and VEGF levels in the retina and optic nerve. We then
      proved that NGF eye drop administration exerts a protective effect on these
      models of retinal degeneration. In brief, our findings indicate that NGF can play
      a protective role against RGC degeneration occurring in GL and DR and suggest
      that ocular NGF administration might be an effective pharmacological approach.

PMID- 21952155
TI  - Signaling pathway-focused gene expression profiling in pressure overloaded
      hearts.
AB  - The beta-blocker propranolol displays antihypertrophic and antifibrotic
      properties in the heart subjected to pressure overload. Yet the underlying
      mechanisms responsible for these important effects remain to be completely
      understood. The purpose of this study was to determine signaling pathway-focused
      gene expression profile associated with the antihypertrophic action of
      propranolol in pressure overloaded hearts. To address this question, a focused
      real-time PCR array was used to screen left ventricular RNA expression of 84 gene
      transcripts representative of 18 different signaling pathways in C57BL/6 mice
      subjected to transverse aortic constriction (TAC) or sham surgery. On the surgery
      day, mice received either propranolol (80 mg/kg/day) or vehicle for 14 days. TAC
      caused a 49% increase in the left ventricular weight-to-body weight (LVW/BW)
      ratio without changing gene expression. Propranolol blunted LVW/BW ratio increase
      by approximately 50% while causing about a 3-fold increase in the expression of
      two genes, namely Brca1 and Cdkn2a, belonging to the TGF-beta and estrogen
      pathways, respectively. In conclusion, after 2 weeks of pressure overload, TAC
      hearts show a gene expression profile superimposable to that of sham hearts.
      Conversely, propranolol treatment is associated with an increased expression of
      genes which negatively regulate cell cycle progression. It remains to be
      established whether a mechanistic link between gene expression changes and the
      antihypertrophic action of propranolol occurs.

PMID- 21952156
TI  - Mortality study in an asbestos cement factory in Naples, Italy.
AB  - The objective of this paper is to investigate mortality among 1247 male asbestos
      cement workers employed in an asbestos-cement plant located in Naples. The cohort
      included 1247 men hired between 1950 and 1986. The follow-up began on January 1st
      1965. The vital status and causes of death were ascertained up to December 31
      2005. Cause-specific mortality rates of the Campania Region population were used
      as reference. Relative risks were estimated using Standardized Mortality Ratios
      (SMRs), and the confidence intervals were calculated at a 95% level (95% CI). A
      significant increase in mortality was observed for respiratory disease (81
      deaths; SMR = 187; 95% CI = 149- 233), particularly for pneumoconiosis (42
      deaths; SMR = 13 313; 95% CI = 9595-17 996) of which 41 deaths for asbestosis
      (SMR = 43 385; 95% CI = 31 134-58 857), for pleural cancer (24 deaths; SMR =
      2617; 95% CI = 1677-3893), for lung cancer (84 deaths; SMR=153; 95% CI = 122-189)
      and for peritoneal cancer (9 deaths; SMR = 1985; 95% CI = 908-3769). Non
      significant increases were also observed for rectum cancer (6 deaths; SMR = 157;
      95% CI = 58-342). In conclusion, consistently with other mortality studies on
      asbestos-cement workers performed in different countries, an increased mortality
      from asbestosis, lung cancer, pleural and peritoneal mesothelioma was detected in
      the present cohort.

PMID- 21952157
TI  - Focus on coal power station installations and population health.
AB  - Damage to health associated with emissions from coal power stations can vary
      greatly from one location to another depending on the size of the plant, location
      and the characteristics of the population. Population-based studies conducted by
      independent groups in different locations around the world show effects on health
      in populations at higher risk, but failed to definitely demonstrate direct
      effects on morbidity and mortality, to be exclusively attributed to the presence
      of active power stations. However, evidence on the role of micropollutants from
      power station activities suggests that a complete and thorough analysis should be
      made on the environmental cycle. Therefore danger should in any case be assessed
      as carefully as possible while assuming, at most, that all micropollutants may
      come into direct contact with man through the various potential pathways
      throughout their entire lifetime, regardless of the factors that reduce their
      presence.

PMID- 21952158
TI  - Persistent organic pollutants (POPs) in fish collected from the urban tract of
      the river Tiber in Rome (Italy).
AB  - European eel and chub samples were analyzed to determine the levels of non-dioxin
      like polychlorobiphenyls (NDL-PCBs), polychlorodibenzodioxins (PCDDs) and
      polychlorodibenzofurans (PCDFs), dioxin-like PCBs (DL-PCBs), and brominated
      polybromodiphenyl ethers (PBDEs) in order to evaluate the extent of contamination
      of the river Tiber along the urban tract through the city of Rome (Italy). All
      samples presented detectable levels of the chemicals analyzed, and exhibited
      species-specific differences in terms of congener composition and total
      concentrations. On average the European eel presented the highest values. In this
      species the dioxin-like compound sums (WHO-TEQs) exceeded the pertinent maximum
      levels (MLs). Non-ortho PCBs constituted approximately 80% of WHO-TEQ
      toxicological potential whereas NDL-PCB and PBDE concentrations appeared to match
      values determined in other polluted aquatic ecosystems where non-point
      contamination sources were present. The contamination patterns determined in fish
      tissues seemed to reflect the impact of generic contamination source(s).

PMID- 21952159
TI  - Proposal for a new detection method of substance abuse risk in Croatian
      adolescents.
AB  - One of the most important factors of successful substance abuse treatment is the
      early start of the same treatment. Recent selection method for identification of
      Croatian adolescents in the substance abuse risk that has been using drug tests
      from urine samples, has been simple and exact on the one hand, but on the other,
      has been very rare and usually guided by the pressure of parents or the court.
      Besides, such method presented the source of legal and ethical questions. So, the
      proposal of application of standardized psychological tests during systematic
      medical exams of Croatian adolescents at the age range of 15-22 years could help
      with the early detection of those adolescents who were in the substance abuse
      risk or already had the developed addiction problem.

PMID- 21952160
TI  - Echocardiographic investigations of myocardial function in mitral stenosis:
      making sense of the echolalia.

PMID- 21952161
TI  - Development of the physical activity index as a measure of total activity load
      and total kilocalorie expenditure during submaximal walking.
AB  - BACKGROUND: Pedometers are most accurate at measuring steps, less accurate at
      estimating distance, and even less accurate at estimating kilocalorie
      expenditure. The purpose of this investigation was to create a Physical Activity
      Index (PAI) using pedometer step counts and rating of perceived exertion (RPE) to
      enhance the ability to estimate kilocalorie expenditure during walking exercise.
      METHODS: Thirty-two females performed 3 counterbalanced walking bouts. During
      each bout, oxygen consumption, RPE, and step counts were measured. The PAI was
      calculated as the product of RPE and step count for each of the bouts. RESULTS:
      Concurrent validation of the PAI was established using VO2 as the criterion
      variable. A multiple regression analysis revealed a strong, positive relation
      between PAI score and VO2 (r=.91). Data were then used to develop a statistical
      model to estimate kcal expenditure using the PAI score as the predictor variable.
      CONCLUSION: The PAI was found to be an accurate method of estimating kcal
      expenditure and is a simple, unobtrusive and inexpensive tool which may be used
      in public health settings.

PMID- 21952162
TI  - An aryl-phosphonate appended macrocyclic platform for lanthanide based bimodal
      imaging agents.
AB  - Four ligand systems have been prepared whose characteristics are well suited to
      the design of bimodal MRI and luminescence probes. The lanthanide complexes
      display high relaxivities and luminescence quantum yields. These properties are
      retained at higher magnetic fields and in a range of competitive environments
      including model extracellular medium and cultured cells.

PMID- 21952163
TI  - Cardioprotective effects of low-dose cyclosporin A added to histidine-tryptophan
      ketoglutarate cardioplegia solution prior to total myocardial ischemia: an in
      vitro rabbit heart study.
AB  - BACKGROUND/AIMS: Mitochondrial permeability transition pore (MPTP) opening
      appears to play a key role in myocardial cell survival after ischemia-reperfusion
      injury and can be inhibited by cyclosporin A (CsA). We investigated whether low
      dose CsA added to histidine-tryptophan-ketoglutarate (HTK) cardioplegia solution
      could improve myocardial protection during longer periods of global myocardial
      ischemia as encountered during cardiac surgery. METHODS: Rabbit hearts perfused
      on a Langendorff apparatus were arrested with cold HTK solution containing 1
      MUmol/l CsA. After 90 min of ischemia, the hearts were reperfused and pmax, max
      dp/dt, min dp/dt, myocardial stiffness, pO(2), coronary flow and heart rate
      recorded. Tissue ATP and malondialdehyde (MDA) were measured to assess cell
      energy content and oxidative stress, respectively. RESULTS: CsA-treated hearts
      recovered pmax (p = 0.026), max dp/dt (p = 0.028) and min dp/dt (p = 0.025) more
      quickly and to a greater extent than non-treated hearts. They required markedly
      less oxygen (p = 0.041) in the first 10 min of reperfusion. Hearts treated with
      CsA produced 44% less MDA (1.09 vs. 1.93, p = 0.008), while ATP levels were
      unchanged. CONCLUSIONS: HTK cardioplegia solution containing CsA at a dose well
      below that expected to cause systemic immunosuppressive effects leads to a
      significant and timelier recovery of myocardial contractility, while consuming
      less oxygen.

PMID- 21952165
TI  - Aire controls mesenchymal stem cell-mediated suppression in chronic colitis.
AB  - Mesenchymal stem cells (MSCs) are emerging as a promising immunotherapeutic,
      based largely on their overt suppression of T lymphocytes under inflammatory and
      autoimmune conditions. While paracrine cross-talk between MSCs and T cells has
      been well-studied, an intrinsic transcriptional switch that programs MSCs for
      immunomodulation has remained undefined. Here we show that bone marrow-derived
      MSCs require the transcriptional regulator Aire to suppress T cell-mediated
      pathogenesis in a mouse model of chronic colitis. Surprisingly, Aire did not
      control MSC suppression of T cell proliferation in vitro. Instead, Aire reduced T
      cell mitochondrial reductase by negatively regulating a proinflammatory cytokine,
      early T cell activation factor (Eta)-1. Neutralization of Eta-1 enabled Aire(-/-)
      MSCs to ameliorate colitis, reducing the number of infiltrating effector T cells
      in the colon, and normalizing T cell reductase levels. We propose that Aire
      represents an early molecular switch imposing a suppressive MSC phenotype via
      regulation of Eta-1. Monitoring Aire expression in MSCs may thus be a critical
      parameter for clinical use.

PMID- 21952166
TI  - Rational design of therapeutic siRNAs: minimizing off-targeting potential to
      improve the safety of RNAi therapy for Huntington's disease.
AB  - RNA interference (RNAi) provides an approach for the treatment of many human
      diseases. However, the safety of RNAi-based therapies can be hampered by the
      ability of small inhibitory RNAs (siRNAs) to bind to unintended mRNAs and reduce
      their expression, an effect known as off-target gene silencing. Off-targeting
      primarily occurs when the seed region (nucleotides 2-8 of the small RNA) pairs
      with sequences in 3'-UTRs of unintended mRNAs and directs translational
      repression and destabilization of those transcripts. To date, most therapeutic
      RNAi sequences are selected primarily for gene silencing efficacy, and later
      evaluated for safety. Here, in designing siRNAs to treat Huntington's disease
      (HD), a dominant neurodegenerative disorder, we prioritized selection of
      sequences with minimal off-targeting potentials (i.e., those with a scarcity of
      seed complements within all known human 3'-UTRs). We identified new promising
      therapeutic candidate sequences which show potent silencing in cell culture and
      mouse brain. Furthermore, we present microarray data demonstrating that off
      targeting is significantly minimized by using siRNAs that contain "safe" seeds,
      an important strategy to consider during preclinical development of RNAi-based
      therapeutics.

PMID- 21952167
TI  - Systemic administration of combinatorial dsiRNAs via nanoparticles efficiently
      suppresses HIV-1 infection in humanized mice.
AB  - We evaluated the in vivo efficacy of structurally flexible, cationic PAMAM
      dendrimers as a small interfering RNA (siRNA) delivery system in a Rag2(-)/
      gammac-/- (RAG-hu) humanized mouse model for HIV-1 infection. HIV-infected
      humanized Rag2-/-gammac-/- mice (RAG-hu) were injected intravenously (i.v.) with
      dendrimer-siRNA nanoparticles consisting of a cocktail of dicer substrate siRNAs
      (dsiRNAs) targeting both viral and cellular transcripts. We report in this study
      that the dendrimer-dsiRNA treatment suppressed HIV-1 infection by several orders
      of magnitude and protected against viral induced CD4(+) T-cell depletion. We also
      demonstrated that follow-up injections of the dendrimer-cocktailed dsiRNAs
      following viral rebound resulted in complete inhibition of HIV-1 titers.
      Biodistribution studies demonstrate that the dendrimer-dsiRNAs preferentially
      accumulate in peripheral blood mononuclear cells (PBMCs) and liver and do not
      exhibit any discernable toxicity. These data demonstrate for the first time
      efficacious combinatorial delivery of anti-host and -viral siRNAs for HIV-1
      treatment in vivo. The dendrimer delivery approach therefore represents a
      promising method for systemic delivery of combinations of siRNAs for treatment of
      HIV-1 infection.

PMID- 21952168
TI  - Optimization of hCFTR lung expression in mice using DNA nanoparticles.
AB  - Efficient and prolonged human cystic fibrosis transmembrane conductance regulator
      (hCFTR) expression is a major goal for cystic fibrosis (CF) lung therapy. A hCFTR
      expression plasmid was optimized as a payload for compacted DNA nanoparticles
      formulated with polyethylene glycol (PEG)-substituted 30-mer lysine peptides. A
      codon-optimized and CpG-reduced hCFTR synthetic gene (CO-CFTR) was placed in a
      polyubiquitin C expression plasmid. Compared to hCFTR complementary DNA (cDNA),
      CO-CFTR produced a ninefold increased level of hCFTR protein in transfected
      HEK293 cells and, when compacted as DNA nanoparticles, produced a similar
      improvement in lung mRNA expression in Balb/c and fatty acid binding protein
      promoter (FABP) CF mice, although expression duration was transient. Various
      vector modifications were tested to extend duration of CO-CFTR expression. A
      novel prolonged expression (PE) element derived from the bovine growth hormone
      (BGH) gene 3' flanking sequence produced prolonged expression of CO-CFTR mRNA at
      biologically relevant levels. A time course study in the mouse lung revealed that
      CO-CFTR mRNA did not change significantly, with CO-CFTR/mCFTR geometric mean
      ratios of 94% on day 2, 71% on day 14, 53% on day 30, and 14% on day 59.
      Prolonged CO-CFTR expression is dependent on the orientation of the PE element
      and its transcription, is not specific to the UbC promoter, and is less dependent
      on other vector backbone elements.

PMID- 21952169
TI  - Hepatitis C virus NS3/NS4A DNA vaccine induces multiepitope T cell responses in
      rhesus macaques mimicking human immune responses [corrected].
AB  - Numerous studies have suggested that an effective hepatitis C virus (HCV) vaccine
      must induce a strong T helper 1 (Th1) T cell response. While several therapeutic
      vaccine candidates have shown promise in clinical trials, response rates have
      been low suggesting that further optimization is important. However, such
      optimization has been hindered by a lack of a benchmark animal model in which to
      test vaccine-induced immune responses before clinical evaluation. The goal of
      this study was to analyze the utility of the rhesus macaque vaccination model in
      assessing HCV vaccine-induced T cell responses. To test this, we employed the use
      of a novel HCV genotype 1a/1b consensus DNA vaccine encoding both HCV
      nonstructural protein 3 (NS3) and nonstructural protein 4A (NS4A) proteins.
      Following immunization, rhesus macaques mounted HCV-specific responses strikingly
      similar to those reported in resolving patients, including strong NS3-specific
      interferon-gamma (IFN-gamma) responses, robust CD4(+) and CD8(+) T cell
      proliferation, and induction of polyfunctional T cells. Additionally, fine
      epitope mapping revealed one animal that mounted a T cell response against a
      known HCV NS3 human leukocyte antigen A2 (HLA-A2) epitope previously identified
      in humans. Taken together our findings suggest that the rhesus macaque
      vaccination model is a useful tool in the evaluation of immune responses induced
      by HCV immunogens.

PMID- 21952170
TI  - A shift from cell cultures to creatures: in vivo imaging of small animals in
      experimental regenerative medicine.
AB  - Although the use of small animals for in vivo experimentation has been
      widespread, only recently has there been easy availability of techniques that
      allow noninvasive in vivo imaging of small animals. Because these techniques
      allow the same individual subject to be followed longitudinally throughout the
      duration of an experiment, their use is rapidly changing the way small animals
      are employed in the laboratory. In this review, we focus on six imaging
      modalities that are increasingly employed for small animal in vivo imaging:
      optical imaging (OI), magnetic resonance imaging (MRI), computed tomography (CT),
      single-photon emission tomography (SPECT), ultrasound (US), and positron-emission
      tomography (PET). Each modality allows for the noninvasive tracking of cells and
      cell products in vivo. In addition, multimodality imaging, combining two or more
      of these techniques, has also been increasingly employed to overcome the
      limitations of each independent technique. After reviewing these available
      imaging modalities, we detail their experimental application, exemplified by the
      emerging field of regenerative medicine, referring to publications whose
      conclusions would otherwise be difficult to support without the availability of
      in vivo imaging.

PMID- 21952172
TI  - Synthesis of Fe3O4-graphene-TiO2 ternary composite networks for enhanced capture
      of phosphopeptides.
AB  - Fe(3)O(4)-graphene-TiO(2) ternary composite networks were first synthesized,
      which exhibited high selectivity and capacity in the capture of phosphopeptides,
      due to the enhanced contact to phosphopeptides given by the graphene scaffold.

PMID- 21952171
TI  - Hematopoietic stem cell mobilization for gene therapy of adult patients with
      severe beta-thalassemia: results of clinical trials using G-CSF or plerixafor in
      splenectomized and nonsplenectomized subjects.
AB  - The safety and efficacy of hematopoietic stem cell (HSC) mobilization was
      investigated in adult splenectomized (SPL) and non-SPL patients with thalassemia
      major, in two clinical trials, using different mobilization modes: granulocyte
      colony-stimulating factor (G-CSF)-alone, G-CSF following pretreatment with
      hydroxyurea (HU), plerixafor-alone. G-CSF-mobilization was both safe and
      effective in non-SPL patients. However, in SPL patients the procedure resulted in
      excessive response to G-CSF, expressed as early hyperleukocytosis necessitating
      significant dose reduction, and suboptimal CD34(+) cells yields. One-month HU
      pretreatment prevented hyperleukocytosis and allowed successful CD34(+) cell
      collections when an optimal washout period was maintained, but it significantly
      prolonged the mobilization procedure. Plerixafor resulted in rapid and effective
      mobilization in both SPL and non-SPL patients and was well-tolerated. For gene
      therapy of thalassemia, G-CSF or Plerixafor could be used as mobilization agents
      in non-SPL patients whereas Plerixafor appears to be the mobilization agent of
      choice in SPL adult thalassemics in terms of safety and efficacy.

PMID- 21952173
TI  - From laboratory to bedside: ethical, legal and social issues in translational
      research.

PMID- 21952174
TI  - The harmful, nontherapeutic use of animals in research is morally wrong.
AB  - It is argued that using animals in research is morally wrong when the research is
      nontherapeutic and harmful to the animals. This article discusses methods of
      moral reasoning and discusses how arguments on this and other bioethical issues
      might be defended and critiqued. A basic method of moral argument analysis is
      presented and used to show that common objections to the view that "animal
      research is morally wrong" fail: ie, common arguments for the view that "animal
      research is morally permissible" are demonstrably unsound or in need of defense.
      It is argued that the best explanations why harmful, nontherapeutic research on
      human beings is wrong, ie, what it is about humans that makes such
      experimentation wrong, apply to many animals as well. Thus, harmful and
      nontherapeutic animal experimentation is wrong for reasons similar to the reasons
      that harmful and nontherapeutic human experimentation is wrong.

PMID- 21952175
TI  - Patients are not rodents writ large.

PMID- 21952176
TI  - What does built-in software of home ventilators tell us? An observational study
      of 150 patients on home ventilation.
AB  - BACKGROUND: Recent home ventilators are equipped with built-in software which
      provides data such as compliance, estimations of leaks, tidal volume, minute
      ventilation, respiratory rate, apnea and apnea-hypopnea indexes, and percentage
      of inspirations triggered by the patient (or ventilator). However, for many of
      these variables, there is neither consensus nor documentation as to what is to be
      expected in a population of stable patients under noninvasive ventilation (NIV).
      OBJECTIVES: To document the values and distribution of specific items downloaded
      from ventilator monitoring software, by diagnostic category. METHODS: Analysis of
      data downloaded from home ventilators in clinically stable patients under long
      term NIV, during elective home visits by specialized nurses. RESULTS: Data were
      collected from home ventilators of 150 patients with chronic obstructive
      pulmonary disease (n = 32), overlap syndrome (n = 29), obesity-hypoventilation (n
      = 38), neuromuscular disorders (n = 19), restrictive disorders (n = 21), and
      central sleep apnea syndrome (n = 11). On average, leaks were low, being lowest
      in patients with facial masks (vs. nasal masks), and increased with older age.
      Compliance was excellent in all groups. Patients with neuromuscular diseases
      triggered their ventilators less and tended to be 'captured', while other groups
      triggered at least half of inspiratory cycles. Most patients had a respiratory
      rate just slightly above the back-up rate. Residual apneas and hypopneas were
      highest in patients with central apneas. CONCLUSIONS: Built-in software of home
      ventilators provides the clinician with new parameters, some of which are a
      useful adjunct to recommended tools for monitoring NIV and may contribute to a
      better understanding of residual hypoventilation and/or desaturations. However,
      an independent validation of the accuracy of this information is mandatory.

PMID- 21952177
TI  - Tuning the emissive triplet excited states of platinum(II) Schiff base complexes
      with pyrene, and application for luminescent oxygen sensing and triplet-triplet
      annihilation based upconversions.
AB  - Pt(II) Schiff base complexes containing pyrene subunits were prepared using the
      chemistry-on-complex approach. This is the first time that supramolecular
      photochemical approach has been used to tune the photophysical properties of
      Schiff base Pt(II) complexes, such as emission wavelength and lifetimes. The
      complexes show intense absorption in the visible region (epsilon = 13100 M(-1)
      cm(-1) at 534 nm) and red phosphorescence at room temperature. Notably, much
      longer triplet excited state lifetimes (tau = 21.0 MUs) were observed, compared
      to the model complexes (tau = 4.4 MUs). The extension of triplet excited state
      lifetimes is attributed to the establishment of equilibrium between the metal-to
      ligand charge-transfer ((3)MLCT) state (coordination centre localized) and the
      intraligand ((3)IL) state (pyrene localized), or population of the long-lived
      (3)IL triplet excited state. These assignments were fully rationalized by
      nanosecond time-resolved difference absorption spectra, 77 K emission spectra and
      density functional theory calculations. The complexes were used as triplet
      sensitizers for triplet-triplet-energy-tranfer (TTET) processes, i.e. luminescent
      O(2) sensing and triplet-triplet annihilation (TTA) based upconversion. The O(2)
      sensitivity (Stern-Volmer quenching constant) of the complexes was quantitatively
      evaluated in polymer films. The results show that the O(2) sensing sensitivity of
      the pyrene containing complex (K(SV) = 0.04623 Torr(-1)) is 15-fold of the model
      complex (K(SV) = 0.00313 Torr(-1)). Furthermore, significant TTA upconversion
      (upconversion quantum yield Phi(UC) = 17.7% and the anti-Stokes shift is 0.77 eV)
      was observed with pyrene containing complexes being used as triplet sensitizers.
      Our approach to tune the triplet excited states of Pt(II) Schiff base complexes
      will be useful for the design of phosphorescent transition metal complexes and
      their applications in light-harvesting, photovoltaics, luminescent O(2) sensing
      and upconversion, etc.

PMID- 21952178
TI  - Liquid structures of water, methanol, and hydrogen fluoride at ambient conditions
      from first principles molecular dynamics simulations with a dispersion corrected
      density functional.
AB  - Using first principles molecular dynamics simulations in the isobaric-isothermal
      ensemble (T = 300 K, p = 1 atm) with the Becke-Lee-Yang-Parr exchange/correlation
      functional and a dispersion correction due to Grimme, the hydrogen bonding
      networks of pure liquid water, methanol, and hydrogen fluoride are probed.
      Although an accurate density is found for water with this level of electronic
      structure theory, the average liquid densities for both hydrogen fluoride and
      methanol are overpredicted by 50 and 25%, respectively. The radial distribution
      functions indicate somewhat overstructured liquid phases for all three compounds.
      The number of hydrogen bonds per molecule in water is about twice as high as for
      methanol and hydrogen fluoride, though the ratio of cohesive energy over number
      of hydrogen bonds is lower for water. An analysis of the hydrogen-bonded
      aggregates revealed the presence of mostly linear chains in both hydrogen
      fluoride and methanol, with a few stable rings and chains spanning the simulation
      box in the case of hydrogen fluoride. Only an extremely small fraction of smaller
      clusters was found for water, indicating that its hydrogen bond network is
      significantly more extensive. A special form of water with on average about two
      hydrogen bonds per molecule yields a hydrogen-bonding environment significantly
      different from the other two compounds.

PMID- 21952179
TI  - Periventricular white matter injury by primary intraventricular hemorrhage: a
      diffusion tensor imaging study.
AB  - OBJECTIVES: Intraventricular hemorrhage (IVH) in adult stroke patients is known
      to be an independent risk factor for poor functional outcome. Using diffusion
      tensor imaging (DTI), we attempted to investigate the effect of IVH on the white
      matter. METHODS: We recruited 10 consecutive patients with IVH and 18 age- and
      sex-matched control subjects. Using a 1.5-T Philips Gyroscan Intera system, DTI
      data was acquired at an average of 84 days (range: 38-149) after IVH onset. We
      measured fractional anisotropy (FA) and apparent diffusion coefficient (ADC)
      values at the fornix, corpus callosum (CC), corona radiata (CR), and posterior
      limb of the internal capsule (PL). In addition, integrity and fiber number were
      measured for the fornix. RESULTS: DTI revealed disruption of the fornix in all
      patients. FA values showed a decrease in the fornix, CC, and CR; in contrast, the
      ADC value showed an increase in the CC, without changes in the fornix or CR.
      Fiber number of the fornix also decreased. However, no change was observed in the
      PL. CONCLUSIONS: We found periventricular white matter (fornix, CC, and CR)
      injury following IVH. We think that this result would be helpful in the
      establishment of management strategies for patients with IVH.

PMID- 21952180
TI  - Effects of resistance training and dietary changes on physical function and body
      composition in overweight and obese older adults.
AB  - BACKGROUND: Community-based interventions that incorporate resistance training
      (RT) and dietary changes have not been extensively studied in overweight and
      obese older adults. The purpose of this investigation was to determine the
      effects of a community-based RT and dietary intervention on physical function and
      body composition in overweight and obese older adults. METHODS: Ninety-five
      overweight and obese (BMI=33.4+/-4.0 kg/m2) older adults aged 55-80 years
      completed an 8-week RT and dietary intervention at 4 Rhode Island senior centers.
      Participants performed RT twice-weekly using resistance tubing, dumbbells, and
      ankle weights. Participants also attended 1 weekly dietary counseling session on
      a modified Dietary Approaches to Stop Hypertension diet. Outcome measurements
      included anthropometrics, body composition, and physical function. RESULTS: There
      were small changes in body mass (-1.0+/-1.8 kg, P<.001), waist circumference (
      5.2+/-3.8 cm, P<.001), and percent body fat (-0.5+/-1.4%, P<.001). In addition,
      significant improvements were observed in knee extensor torque (+7.9+/-19.1 N-m,
      P<.001), handgrip strength (+1.2+/-2.5 kg, P<.001), and 8-foot up-and-go test
      time (-0.56+/-0.89 s, P<.001). CONCLUSION: Community-based RT and dietary
      modifications can improve body composition, muscle strength, and physical
      function in overweight and obese older adults. Future investigations should
      determine if this intervention is effective for long-term changes.

PMID- 21952181
TI  - Chronic low back pain: a heterogeneous condition with challenges for an evidence
      based approach.
AB  - "Chronic" low back pain (LBP), defined as present for 3 or more months, has
      become a major socioeconomic problem insufficiently addressed by five major
      entities largely working in isolation from one another - procedural based
      specialties, strength based rehabilitation, cognitive behavioral therapy, pain
      management and manipulative care. As direct and indirect costs continue to rise,
      many authors have systematically evaluated the body of evidence in an effort to
      demonstrate the effectiveness (or lack thereof) for various diagnostic and
      therapeutic interventions. The objective of this Spine Focus issue is not to
      replicate previous work in this area. Rather, our expert panel has chosen a set
      of potentially controversial topics for more in-depth study and discussion. A
      recurring theme is that chronic LBP is a heterogeneous condition, and this
      affects the way it is diagnosed, classified, treated, and studied. The efficacy
      of some treatments may be appreciated only through a better understanding of
      heterogeneity of treatment effects (i.e., identification of clinically relevant
      subgroups with differing responses to the same treatment). Current clinical
      guidelines and payer policies for LBP are systematically compared for consistency
      and quality. Novel approaches for data gathering, such as national spine
      registries, may offer a preferable approach to gain meaningful data and direct us
      towards a "results-based medicine." This approach would require more high-quality
      studies, more consistent recording for various phenotypes and exploration of
      studies on genetic epidemiologic undertones to guide us in the emerging era of
      "results based medicine."

PMID- 21952182
TI  - Methodology for the systematic reviews on an evidence-based approach for the
      management of chronic low back pain.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: To provide a detailed description of
      the methods undertaken in the systematic search and analytical summary of chronic
      low back pain (CLBP) management issues and to describe the process used to
      develop clinical recommendations regarding challenges in the management of
      patients with CLBP. SUMMARY OF BACKGROUND DATA: We present methods used in
      conducting the systematic, evidence-based reviews and development of expert panel
      recommendations on key challenges to CLBP assessment and management. Our intent
      is that clinicians will combine the information from these reviews with an
      understanding of their own capacities and experience to better manage patients
      with chronic LBP and to consider future research that identifies patients or
      subgroups that respond differently with regard to benefits and safety to various
      treatment interventions. METHODS: A systematic search and critical review of the
      English language literature was undertaken for articles published on the
      classification, measurement, and management of CLBP. Citations were screened for
      relevance using a priori criteria, and relevant studies were critically reviewed.
      Whether an article was included for review depended on whether the study question
      was descriptive, one of therapy, one of prognosis, or one of diagnosis. When
      evaluating differential treatment benefits by specific disease, sociodemographic,
      and psychological subgroups, we sought to evaluate the heterogeneity of treatment
      effects. Studies were included if they made the treatment comparison and
      presented treatment effects by the predefined subgroup. The strength of evidence
      for the overall body of literature in each topic area was determined by two
      independent reviewers considering risk of bias, consistency, directness, and
      precision of results using a modification of the Grades of Recommendation
      Assessment, Development and Evaluation (GRADE) criteria. Disagreements were
      resolved by consensus. Findings from studies meeting inclusion criteria were
      summarized. From these summaries, clinical recommendations were formulated from
      consensus achieved among subject experts through a modified Delphi process.
      RESULTS: We identified and screened 2845 citations in 13 topic areas relating to
      the classification, measurement, and management of CLBP. Of these, 118 met our
      predetermined inclusion criteria and were used to attempt to answer specific
      clinical questions within each topic area. Some of the highlights of the analysis
      revealed a limited number of studies meeting inclusion criteria for topics
      evaluating therapy, use of magnetic resonance imaging, and classification
      systems. Few studies comparing surgical fusion to nonoperative care were
      identified that presented treatment effects by subgroups limiting the evaluation
      of heterogeneity of treatment effects. CONCLUSION: We undertook systematic
      reviews to understand the classification, measurement, and management of CLBP and
      to provide clinical recommendations. This article reports the methods used in the
      reviews. CLINICAL RECOMMENDATIONS: Clinical recommendations were made where
      appropriate using the GRADE/Agency for Healthcare Research and Quality approach,
      which imparts a deliberate separation between the quality of the evidence (i.e.,
      high, moderate, low, or inconclusive) from the strength of the recommendation.
      The quality of evidence plays only a part as the strength of the recommendation
      reflects the extent to which we can, across the range of patients for whom the
      recommendations are intended, be confident that desirable effects of a management
      strategy outweigh undesirable effects.

PMID- 21952183
TI  - Effectiveness of spinal fusion versus structured rehabilitation in chronic low
      back pain patients with and without isthmic spondylolisthesis: a systematic
      review.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: To determine if the presence of
      isthmic spondylolisthesis modifies the effect of treatment (fusion vs.
      multidimensional supervised rehabilitation) in patients with chronic low back
      pain (CLBP). SUMMARY OF BACKGROUND DATA: Results of spinal surgery for CLBP are
      variable. It is unclear whether patients with CLBP and isthmic spondylolisthesis
      have more success with surgery versus a multidimensional supervised
      rehabilitation program when compared with those with CLBP but without
      spondylolisthesis. METHODS: A systematic search was conducted in MEDLINE and the
      Cochrane Collaboration Library for articles published through January 2011.
      Randomized controlled trials (RCTs) were included that compared spine fusion
      versus multidimensional supervised rehabilitation in patients with and without
      isthmic spondylolisthesis. Standardized mean differences (SMDs) and risk
      differences were calculated for common outcomes, and then compared to determine
      potential heterogeneity of treatment effect. The final strength of the body of
      literature was expressed as "high," "moderate," or "low" confidence that the
      evidence reflects the true effect. RESULTS: No studies were found that directly
      compared the two subgroups. Three RCTs compared fusion with supervised
      nonoperative care in patients with CLBP without isthmic spondylolisthesis; one
      RCT evaluated these treatments in patients with isthmic spondylolisthesis. There
      were study differences in patient characteristics, type of fusion, the nature of
      the rehabilitation, outcomes assessed, and length of follow-up. The SMDs for pain
      in favor of fusion were modest at 2 years for those without isthmic
      spondylolisthesis, but large in favor of fusion for those with isthmic
      spondylolisthesis compared with rehabilitation. Similarly, the SMDs for function
      in patients without isthmic spondylolisthesis compared with rehabilitation was
      small at 2 years, but appreciably higher in favor of fusion in patients with
      isthmic spondylolisthesis. CONCLUSION: The overall strength of evidence
      evaluating whether the presence of isthmic spondylolisthesis modifies the effect
      of fusion compared with rehabilitation patients with CLBP is "low." Fusion should
      be considered for patients with low back pain and isthmic spondylolisthesis who
      have failed nonoperative treatment. CLINICAL RECOMMENDATIONS: We recommend
      considering fusion for patients with isthmic spondylolisthesis and lower back
      pain who have failed nonoperative treatment. RECOMMENDATION: Weak.

PMID- 21952184
TI  - Comparative effectiveness of exercise, acupuncture, and spinal manipulation for
      low back pain.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: We sought to answer the following
      clinical questions: (1) Is structured exercise more effective in the treatment of
      chronic low back pain (LBP) than spinal manipulative therapy (SMT)? (2) Is
      structured exercise more effective in the treatment of chronic LBP than
      acupuncture? (3) Is SMT more effective in the treatment of chronic LBP than
      acupuncture? (4) Do certain subgroups respond more favorably to specific
      treatments? (5) Are any of these treatments more cost-effective than the others?
      SUMMARY OF BACKGROUND DATA: Exercise, SMT, and acupuncture are widely used
      interventions in the treatment of chronic LBP. There is evidence that all of
      these approaches may offer some benefit for patients with chronic LBP when
      compared with usual care or no treatment. The relative benefits or cost
      effectiveness of any one of these treatments when compared with the others are
      less well-defined, and it is difficult to identify specific subgroups of those
      with chronic LBP who may preferentially respond to a particular treatment
      modality. METHODS: A systematic review of the literature was performed to
      identify randomized controlled trials comparing a structured exercise program,
      SMT, or acupuncture with one another in patients with chronic LBP. RESULTS: Two
      studies were identified comparing the use of structured exercise with SMT that
      met our inclusion criteria. Although these studies utilized different approaches
      for the exercise and SMT treatment groups, patients in both groups improved in
      terms of pain and function in both studies. Using random-effects modeling, there
      was no difference between the exercise and SMT groups when the data from these
      studies were pooled. We identified no studies meeting our inclusion criteria that
      compared acupuncture with either structured exercise or SMT or that addressed the
      relative cost-effectiveness of these approaches in the treatment of patients with
      chronic LBP. CONCLUSION: The studies identified indicate that structured exercise
      and SMT appear to offer equivalent benefits in terms of pain and functional
      improvement for those with chronic LBP with clinical benefits evident within 8
      weeks of care. However, the level of evidence is low. There is insufficient
      evidence to comment on the relative benefit of acupuncture compared with either
      structured exercise or SMT or to address the differential effects of structured
      exercise, SMT, or acupuncture for specific subgroups of individuals with chronic
      LBP. There is also insufficient evidence regarding the relative cost
      effectiveness of structured exercise, SMT, or acupuncture in the treatment of
      chronic LBP. CLINICAL RECOMMENDATIONS: Structured exercise and SMT appear to
      offer equivalent benefits in the management of pain and function for patients
      with nonspecific chronic LBP. If no clinical benefit is appreciated after using
      one of these approaches for 8 weeks, then the treatment plan should be
      reevaluated and consideration should be given to modifying the treatment approach
      or using alternate forms of care. Strength of recommendation: Weak.There is
      insufficient evidence regarding the relative benefits of the acupuncture compared
      with either structured exercise or SMT in the treatment of chronic LBP.There is
      insufficient evidence to address differential effects of structured exercise,
      SMT, or acupuncture for specific subgroups of individuals with chronic LBP. There
      is insufficient evidence regarding the relative cost-effectiveness of structured
      exercise, SMT, or acupuncture in the treatment of chronic LBP.

PMID- 21952185
TI  - Pharmacologic management of chronic low back pain: synthesis of the evidence.
AB  - STUDY DESIGN: Systematic review of the literature with subgroup analysis for
      heterogeneous treatment effects. OBJECTIVE: The objectives of this systematic
      review were to summarize prior Cochrane reports regarding the safety and
      effectiveness of opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), and
      antidepressants for treatment of chronic low back pain (LBP) and to evaluate
      whether certain subpopulations respond more favorably to pharmacological
      management. SUMMARY OF BACKGROUND DATA: While medications are a mainstay of LBP
      management, there is uncertainty as to the optimal use of commonly prescribed
      medications such as opioids, antidepressants, and NSAIDS. METHODS: To summarize
      the overall treatment effect and safety for each of the three pharmacological
      drug classes (opioids, NSAIDs, or antidepressants), we summarized existing
      Cochrane reviews. To evaluate whether the effects of treatment varied by specific
      subgroups of patients, we sought randomized controlled trials (RCTs) evaluating
      one of the three pharmacological drug classes versus an alternative management
      for chronic LBP. RESULTS: Based on the Cochrane reviews, opioids are more
      effective than placebo with respect to pain and disability, with a much greater
      effect size for pain than disability. When compared with NSAIDs, opioids did not
      confer a greater benefit with regard to pain and disability. The rate of side
      effects from opioids is significantly greater than placebo with differences
      ranging between 2% and 9%. The systematic review of RCTs showed that
      antidepressants are not more effective than placebo with respect to pain,
      functional status, or depression. Certain subgroup treatment effects were
      identified, supporting our hypothesis that chronic LBP should be considered a
      heterogeneous set of disorders. As such, chronic LBP subgroups should be
      considered both when making clinical treatment decisions and when designing
      future research trials. CONCLUSION: Opioids and NSAIDs are effective for chronic
      LBP, while antidepressants have no meaningful clinical benefit. Based on the
      significant rate of side effects with opioids and the lack of convincing
      superiority over NSAIDs, opioids are not recommended as a treatment for chronic
      LBP. Attention to subgroups of patients will likely help guide treatment, and
      will likely help increase the clinical impact of future research. CLINICAL
      RECOMMENDATIONS: Recommendation 1: NSAIDs should be considered as a treatment of
      chronic LBP (Strength: Strong). There is evidence demonstrating favorable
      effectiveness, but also significant side effects that may have meaningful
      clinical consequences. Recommendation 2: Opioids may be considered in the
      treatment of chronic LBP but should be avoided if possible (Strength: Weak).
      There is evidence demonstrating favorable effectiveness compared to placebo,
      similar effectiveness compared to NSAIDs, and with significant side effects
      including decreasing effectiveness related to habituation when used long-term.
      Recommendation 3: Antidepressants should not be routinely used for the treatment
      of chronic LBP (Strength: Strong). There is evidence that they are not more
      effective than placebo with respect to pain, functional status, or depression.
      Based on the hypothesis that chronic LBP is a symptom reflective of a
      heterogeneous group of disorders, categorization of certain patient specific
      subgroups may be helpful in guiding future treatment decision making. It is
      likely that inclusion of subgroup factors in future RCTs will provide information
      needed to improve the strength and specificity of future clinical
      recommendations.

PMID- 21952186
TI  - Clinical guidelines and payer policies on fusion for the treatment of chronic low
      back pain.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: The purpose of this review is to
      provide a critical appraisal of general and fusion-specific clinical practice
      guidelines on the treatment of chronic nonradicular low back pain and compare the
      quality and evidence base of fusion guidelines and select payer policies. SUMMARY
      OF BACKGROUND DATA.: The treatment of lumbar spondylosis associated with low back
      pain with lumbar arthrodesis, or fusion, has risen fourfold in the past two
      decades. Given the significant associated health care costs, there is an increase
      in clinical guidelines and payer policies influencing patient treatment options.
      Assessment of the medical necessity of a treatment, such as lumbar fusions, based
      on medical literature will frequently supersede the determination of the
      physician in the care of their patient. Concerns regarding the effectiveness and
      costs of the surgical treatment of spinal disorders presenting with low back pain
      has placed enormous scrutiny on the value of surgical treatments to our patients.
      As both clinical guidelines and payer policies have a major impact on the
      perceived effectiveness, or medical necessity, of lumbar fusions for the
      treatment of chronic nonradicular low back pain, a review of this topic was
      undertaken. METHODS: An electronic literature search of PubMed, the National
      Guideline Clearinghouse and the International Network of Agencies for Health
      Technology Assessment was performed to identify clinical practice guidelines on
      assessment and treatment of chronic nonradicular low back pain, including those
      on use of lumbar fusion, as well as relevant technology assessments. A Google
      search for publicly available private and public payer policies related to fusion
      was also performed. A hand search was used to identify specific studies cited for
      support of the recommendations made. A modified Appraisal of Guidelines Research
      and Evaluation instrument was used to provide a standardized assessment method
      for evaluating the quality of development of the evidence base and
      recommendations in guidelines and selected health policies. This was combined
      with appraisal of the evidence base supporting the recommendations. RESULTS:
      Three systematic reviews of general guidelines from a PubMed search yielding 94
      citations were included. A convenience sample of five guidelines with
      recommendations on fusion was taken from 182 citations identified by the National
      Guideline Clearinghouse and the International Network of Agencies for Health
      Technology Assessment searches. Two guidelines were developed by US professional
      societies, (neurosurgery and pain management), and three were European-based
      guidelines (Belgium, United Kingdom, and the European Cooperation in Science and
      Technology). The general guidelines were consistent with their recommendations
      for diagnosis, but inconsistent regarding recommendations for treatment. All
      guidelines and payer policies with recommendations on fusion included some set of
      the primary randomized controlled trials comparing fusion to other treatment
      options with the exception of one policy. However, no clear pattern with regard
      to the quality of development was identified based on the modified Appraisal of
      Guidelines Research and Evaluation tool. There were differences in specialty
      society recommendations. CONCLUSION: Three systematic reviews of evidence-based
      guidelines that provide general guidance for the assessment and treatment of
      chronic low back pain described consistent recommendations and guidance for the
      evaluation of chronic low back pain but inconsistent recommendations and guidance
      for treatment. Five evidence-based guidelines with recommendations on the use of
      fusion for the treatment of chronic low back pain were evaluated. There is some
      consistency across guidelines and policies that are government sponsored with
      regard to development process and critical evaluation of index studies as well as
      overall recommendations. There were differences in specialty society
      recommendations. There is heterogeneity in the medical payer policies reviewed
      possibly due to variations in the literature cited and transparency of the
      development process. A description of how recommendations are formulated and
      disclosure of any potential bias in policy development is important. Three
      medical payer policies reviewed are of poor quality with one rated as good with
      respect to their development based on the modified Appraisal of Guidelines
      Research and Evaluation tool. Medical payer policies influence patient care by
      defining medical necessity for approving treatments, and should be held to the
      same standards for transparency and development as guidelines. CLINICAL
      RECOMMENDATIONS: The spine care community needs to develop (or update) high
      quality treatment guidelines. The process should be transparent, methodologically
      rigorous, and consistent with the Appraisal of Guidelines Research and Evaluation
      and Institute of Medicine recommendations. This effort should be collaborative
      across specialty/society groups and would benefit from patient and public input.
      Payer policies and treatment guidelines need to be transparent and based on the
      highest quality evidence available. Clinicians from specialty/society groups,
      guideline developers and policy makers should collaborate on their development.
      This process would also benefit from public and patient input.

PMID- 21952187
TI  - A systematic review of clinical pathways for lower back pain and introduction of
      the Saskatchewan Spine Pathway.
AB  - STUDY DESIGN: Systematic review of spine care pathways and case study of the
      Saskatchewan Spine Pathway (SSP). OBJECTIVE: (1) What are the differences between
      clinical pathways and clinical guidelines? (2) Are there examples of clinical
      pathways in the management of lower back pain (LBP)? Is there evidence that they
      are successful? (3) What is the SSP, and what are its key features? SUMMARY OF
      BACKGROUND DATA: Adherence to evidence-based guidelines for LBP produces superior
      outcomes and may improve efficiency by reducing unnecessary imaging, ineffective
      treatments, and inappropriate surgical referrals. A clinical pathway is an
      attempt to bridge the "translation gap" between guidelines and clinical practice.
      METHODS: A qualitative review was performed for question 1. For question 2, a
      systematic review of the English language literature was performed for articles
      published through March 31, 2011. A case study is provided for question 3.
      RESULTS: (1) Evidence for clinical pathways is mainly derived from guidelines,
      but pathways are distinguished by several features including the coordination of
      multidisciplinary care, facilitation of communication among care providers,
      resources for ongoing quality improvements, and a central focus on the patient
      experience. (2) Five articles describing four clinical pathways met the a priori
      criteria, but none tested comparative effectiveness. (3) The SSP is unique in
      that it is (a) inclusive for all types of LBP, (b) based on a classification
      system, (c) patient-focused mostly at primary care rather than in specialized
      clinics, (d) implemented in the health care system of a geopolitically defined
      region, and (e) includes all of the defining features of modern care pathways.
      CONCLUSION: Several clinical pathways for LBP have been described, but
      effectiveness has not been tested. CLINICAL RECOMMENDATIONS: Clinical pathways
      for LBP need to be further developed and investigated as a means to facilitate
      guidelines-concordant practice and improve patient outcomes. LEVEL OF EVIDENCE:
      Insufficient. RECOMMENDATION: Weak.

PMID- 21952188
TI  - The role of classification of chronic low back pain.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: To describe the various ways chronic
      low back pain (CLBP) is classified, to determine if the classification systems
      are reliable and to assess whether classification-specific interventions have
      been shown to be effective in treating CLBP. SUMMARY OF BACKGROUND DATA: A
      classification system by which individual patients with CLBP could be identified
      and directed to an effective treatment protocol would be beneficial. Those
      systems that direct treatment have the greatest potential influence on patient
      outcomes. METHODS: A systematic search was conducted in MEDLINE and the Cochrane
      Collaboration Library for English language literature published through January
      2011. We included articles that specifically described a clinical classification
      system for CLBP, reported on the reliability of a classification system, or
      evaluated the effectiveness of classification-specific interventions. RESULTS: A
      total of 60 articles were initially reviewed. We identified 28 classification
      systems that met inclusion criteria: 16 diagnostic systems, 7 prognostic systems,
      and 5 treatment-based systems. In addition, we found 10 randomized controlled
      trials of CLBP treatment from which we compared inclusion and exclusion criteria.
      Treatment-based systems were all directed at nonoperative management. Four of the
      5 treatment-based systems underwent reliability testing and were found to have
      interobserver agreement of 70% to 100%. Reliability increased with training and
      familiarity with a given classification. As the number of subgroups within a
      classification increased, interobserver agreement decreased. Function and pain
      were similar between patients treated with the McKenzie classification system and
      those treated with dynamic strengthening training after 8 months of follow-up in
      one randomized controlled trial. One prospective cohort study reported better
      pain and function using the Canadian Back Institute Classification system than
      with standard rehabilitation. An analysis of the admission criteria to recent
      randomized studies with either nonoperative care or another surgical intervention
      provided a methodology for refining criteria to be met by patients considering
      surgery. CONCLUSION: There currently are many classification systems for CLBP;
      some that are descriptive, some prognostic, and some that attempt to direct
      treatment. We recommend that no one classification system be adopted for all
      purposes. We further recommend that future efforts in developing a classification
      system focus on one that helps to direct both surgical and nonsurgical
      treatments. CLINICAL RECOMMENDATIONS: There currently are many classification
      systems for CLBP; some that are descriptive, some prognostic, and some that
      attempt to direct treatment. We recommend that no one classification system be
      adopted for all purposes. We further recommend that future efforts in developing
      a classification system focus on one that helps to direct both surgical and
      nonsurgical treatments.

PMID- 21952189
TI  - Degenerative magnetic resonance imaging changes in patients with chronic low back
      pain: a systematic review.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: To systematically search for
      critically appraise and summarize studies that (1) evaluated the association
      between degenerative magnetic resonance imaging (MRI) changes and chronic low
      back pain (CLBP) and (2) compared surgical and nonsurgical treatment of these
      degenerative MRI changes. SUMMARY OF BACKGROUND DATA: The role of routine MRI in
      patients with CLBP is unclear. It is also uncertain whether or not surgical
      treatment of degenerative MRI changes results in alleviation of back pain.
      METHODS: Systematic literature searches were conducted in PubMed for studies
      published through March 1, 2011. To evaluate whether MRI degenerative changes are
      associated with CLBP, studies that were designed to compare the prevalence of MRI
      changes among subjects with and without CLBP were sought. The prevalence odds
      ratio was used to compare the odds of degenerative MRI findings in subjects with
      CLBP to the odds of such findings among those without CLBP. To evaluate whether
      surgical treatment of degenerative MRI changes is associated with different
      outcomes compared with nonsurgical treatment, comparative studies were sought.
      The GRADE system as applied to describe the strength of the overall body of
      evidence. RESULTS: Regarding the association of degenerative changes on MRI and
      CLBP, five studies were included, all of which were cross-sectional in design. On
      the basis of these studies, a statistically significant association was found in
      all but one study regarding the presence of disc degeneration and CLBP (odds
      ratio range: 1.8-2.8). The overall strength of evidence across studies was
      considered to be insufficient, however. No comparative studies of surgical versus
      nonsurgical treatment of degenerative MRI changes were identified. CONCLUSION:
      Although there may be an association between degenerative MRI changes and CLBP,
      it is unknown if these estimates accurately represent the association given the
      quality of included studies, lack of a direct link between degenerative MRI
      changes and CLBP, and heterogeneity across studies. Thus, a strong recommendation
      against the routine use of MRI for CLBP evaluation is made. Since there are no
      data evaluating the efficacy of the surgical treatment of degenerative MRI
      changes, a strong recommendation is made against the surgical treatment of CLBP
      based solely upon degenerative MRI changes. CLINICAL RECOMMENDATIONS: 
      RECOMMENDATION 1: There is insuffi cient evidence to support the routine use of
      MRI in patients with CLBP. RECOMMENDATION: Strong RECOMMENDATION 2: Surgical
      treatment of CLBP based exclusively on MRI fi ndings of degenerative changes is
      not recommended. RECOMMENDATION: Strong.

PMID- 21952190
TI  - Evaluating common outcomes for measuring treatment success for chronic low back
      pain.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: To identify, describe, and evaluate
      common outcome measures in patients with chronic low back pain (CLBP). SUMMARY OF
      BACKGROUND DATA: The treatment of CLBP has been associated with multiple clinical
      challenges. Further complicating this is the myriad of outcome scores used to
      assess treatment of CLBP. These scores have been used to examine different
      domains of patient satisfaction and quality of life in the literature. Critical
      assessment of the frequency, parity, and the quality of these outcomes are
      essential to improve our understanding of CLBP. METHODS: A systematic review of
      the English-language literature was undertaken for articles published from
      January 2001 through December 31, 2010. Electronic databases and reference lists
      of key articles were searched to identify measures used to evaluate outcomes in
      six different domains in patients with CLBP. The titles and abstracts of the peer
      reviewed literature of LBP were searched to determine which of these measures
      were most commonly reported in the literature and which have been validated in
      populations with CLBP. RESULTS: We identified 75 outcome measures cited to
      evaluate CLBP. Twenty-nine of these outcome measures were excluded because of
      only a single citation leaving 46 measures for the evaluation. The most commonly
      used functional outcomes were the Oswestry Disability Index, Roland Morris
      Disability Index, and range of motion. For pain, the Numeric Pain Rating Scale,
      Brief Pain Inventory, Pain Disability Index, McGill Pain Questionnaire, and
      visual analog scale were most commonly cited. For psychosocial function, the Fear
      Avoidance Beliefs Questionnaire, Tampa Scale for Kinesiophobia, and Beck
      Depression Inventory were most commonly used. For generic quality of life, short
      form 36, Nottingham Health Profile, short form 12, and Sickness Impact Profile
      were the most common measures. For objective measures, the work status/return to
      work, complications or adverse events, and medications used were the most
      commonly cited. For preference-based measures, the Euro-Quol 5 dimensions and
      short form 6 dimensions were most commonly cited. The validity, reliability,
      responsiveness, universality, and potential proprietary requirements are
      summarized for each. CONCLUSION: Outcome measures should be routinely assessed in
      patients with CLBP. The choice of appropriate outcome measure should be
      influenced by the study objectives and design, as well as properties of the
      particular measure within the context of CLBP. CLINICAL RECOMMENDATIONS:
      Recommendation 1: When selecting the appropriate outcome measures for clinical or
      research purposes, consider domains that best measure what are most important to
      patients. Measures that are valid, reliable, and responsive to change should be
      considered first. Other considerations include the number of items required
      (especially in the context of multiple measures), whether the measure is
      validated in the relevant language, and the associated costs or fees. Strength:
      Strong Recommendation 2: Domains of greatest importance include pain, function,
      and quality of life. If cost utilization is a priority, then preference-based
      measures should be considered. For pain, we recommend the VAS and NRPS because of
      their ease of administration and responsiveness. For function, we recommend the
      ODI and RMDQ. The SF-36 and its shorter versions are most commonly used and
      should be considered if quality of life is important. If cost utility is
      important, consider the EQ-5D or SF-6D. Psychosocial tests are best used as
      screening tools prior to surgery because of their lack of responsiveness.
      Complications should always be assessed as a standard of clinical practice.
      Return to work and medication use are complicated outcome measures and not
      recommended unless the specific study question is focused on these domains.
      Consider staff and patient burden when prioritizing one's battery of measures.

PMID- 21952191
TI  - Fusion versus nonoperative management for chronic low back pain: do
      sociodemographic factors affect outcome?
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: The objectives of this systematic
      review were to determine whether sociologic and demographic factors modify the
      effect of fusion versus nonoperative management in patients with chronic low back
      pain. SUMMARY OF BACKGROUND DATA: Chronic low back pain is among the most common
      symptoms leading patients to seek medical care and presents significant
      challenges in treatment decision making. This is due to the wide array of
      pathologic conditions causing back pain, the multitude of patient variables
      (i.e., litigation, psychologic issues, social issues) that are thought to
      influence the perception of back pain, and the wide variation in treatment
      response. Sociodemographic factors are thought to play a role in pain perception
      and treatment response, though this has been poorly assessed in the literature.
      METHODS: Systematic review of the literature, focused on randomized controlled
      trials to assess the heterogeneity of treatment effect of sociodemographic
      factors on the outcomes of fusion versus nonoperative care of the treatment of
      chronic low back pain. RESULTS: The only sociologic factors evaluated in
      randomized controlled trials adequate to assess heterogeneity of treatment effect
      are pending litigation, worker's compensation, sick leave, and heavy labor job
      type. Litigation patients, although thought to do poorly with treatment of
      chronic low back pain in general, responded more favorably to fusion than
      nonoperative care. Likewise, patients with lighter jobs and those patients who
      were not on sick leave did better with fusion than nonoperative care. No
      demographic factors were observed to respond more favorably to one treatment over
      the other. CONCLUSION: Sociodemographic factors are not well studied in the
      literature, but are assumed to affect treatment outcomes. After rigorous review,
      few studies held up to the standards required for defining the comparative
      treatment effect of these factors. Pending litigation may negatively impact
      outcomes of patients with chronic low back pain; however, those who underwent
      fusion had better outcomes than those with nonoperative management in two
      European studies. There is no evidence to suggest that sociodemographic factors
      alone should preclude surgery. Well-constructed prospective randomized studies
      with predefined subgroup analyses are required to further understand the impact
      of sociodemographic factors in the treatment of chronic low back pain. CLINICAL
      RECOMMENDATIONS: Sociodemographic factors should be considered when making
      treatment decisions for patients with chronic low back pain, but alone do not
      preclude fusion for chronic low back pain. Strength of recommendation: Weak.

PMID- 21952192
TI  - Fusion versus nonoperative care for chronic low back pain: do psychological
      factors affect outcomes?
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: The objectives of this systematic
      review were to determine whether fusion is superior to conservative management in
      certain psychological subpopulations and to determine the most common
      psychological screening tests and their ability to predict outcome after
      treatment in patients with chronic lower back pain. SUMMARY OF BACKGROUND DATA:
      Many studies have documented the effects of various psychological disorders on
      outcomes in the treatment of lower back pain. The question of whether patients
      with certain psychological disorders would benefit more from conservative
      treatment than fusion is not clear. Furthermore, the most appropriate screening
      tools for assessing psychological factors in the presence of treatment decision
      making should be recommended. METHODS: Systematic review of the literature,
      focused on randomized controlled trials to assess the heterogeneity of treatment
      effect of psychological factors on the outcomes of fusion versus nonoperative
      care of the treatment of chronic low back pain. In the analysis of psychological
      screening tests, we searched for the most commonly reported questionnaires and
      those that had been shown to predict lower back pain treatment outcomes. RESULTS:
      Few studies comparing fusion to conservative management reported differences in
      outcome by the presence or absence of a psychological disorder. Among those that
      did, we observed the effect of fusion compared with conservative management was
      more favorable in patients without a personality disorder, neuroticism, or
      depression. The most commonly reported, validated psychological screening tests
      for lower back pain are the Beck Depression Inventory, the Fear Avoidance Belief
      Questionnaire, the Spielberger Trait Anxiety Inventory, the Zung Depression
      Scale, and the Distress Risk Assessment Method. CONCLUSION: Psychological
      disorders affect chronic lower back pain treatment outcomes. Patients with a
      personality disorder appear to respond more favorably to conservative management
      and those without a personality disorder more favorably to fusion. Patients with
      higher depression and neuroticism scores may also respond more favorably to
      conservative management. CLINICAL RECOMMENDATIONS: Recommendation 1: Chronic LBP
      patients with depression, neuroticism, and certain personality disorders should
      preferentially be treated nonoperatively. Strength of recommendation: Weak.
      Recommendation 2: Consider the use of a validated psychological screening
      questionnaire such as the BDI, FABQ, DRAM, ZDI or STAI, when treating patients
      with CLBP. Strength of recommendation: Weak.

PMID- 21952193
TI  - The neural basis of the Enigma illusion: a transcranial magnetic stimulation
      study.
AB  - The aim of this study was to test the role of the visual primary (V1) and the
      middle temporal area (V5/MT) in the illusory motion perception evoked by the
      Enigma figure. The Enigma figure induces a visual illusion that is characterized
      by apparent rotatory motion in the presence of a static figure. By means of
      repetitive transcranial magnetic stimulation (rTMS) we show that V5/MT is
      causally linked to the illusory perception of motion. When rTMS was applied
      bilaterally over V5/MT just prior to presentation of the Enigma figure, the
      perception of illusory motion was disrupted for approximately 400 ms resulting in
      a delayed illusion onset. In contrast, rTMS applied over V1 did not have any
      effect on the illusory perception of motion. These results show that V5/MT, a
      visual cortical area associated with real motion perception, is also important
      for the perception of illusory motion, while V1 appears not to be functionally
      involved in illusory motion perception.

PMID- 21952194
TI  - Multimodal alexia: neuropsychological mechanisms and implications for treatment.
AB  - Letter-by-letter (LBL) reading is the phenomenon whereby individuals with
      acquired alexia decode words by sequential identification of component letters.
      In cases where letter recognition or letter naming is impaired, however, a LBL
      reading approach is obviated, resulting in a nearly complete inability to read,
      or global alexia. In some such cases, a treatment strategy wherein letter tracing
      is used to provide tactile and/or kinesthetic input has resulted in improved
      letter identification. In this study, a kinesthetic treatment approach was
      implemented with an individual who presented with severe alexia in the context of
      relatively preserved recognition of orally spelled words, and mildly impaired
      oral/written spelling. Eight weeks of kinesthetic treatment resulted in improved
      letter identification accuracy and oral reading of trained words; however, the
      participant remained unable to successfully decode untrained words. Further
      testing revealed that, in addition to the visual-verbal disconnection that
      resulted in impaired word reading and letter naming, her limited ability to
      derive benefit from the kinesthetic strategy was attributable to a disconnection
      that prevented access to letter names from kinesthetic input. We propose that
      this kinesthetic-verbal disconnection resulted from damage to the left parietal
      lobe and underlying white matter, a neuroanatomical feature that is not typically
      observed in patients with global alexia or classic LBL reading. This unfortunate
      combination of visual-verbal and kinesthetic-verbal disconnections demonstrated
      in this individual resulted in a persistent multimodal alexia syndrome that was
      resistant to behavioral treatment. To our knowledge, this is the first case in
      which the nature of this form of multimodal alexia has been fully characterized,
      and our findings provide guidance regarding the requisite cognitive skills and
      lesion profiles that are likely to be associated with a positive response to
      tactile/kinesthetic treatment.

PMID- 21952195
TI  - Pre-stimulus pattern of activity in the fusiform face area predicts face percepts
      during binocular rivalry.
AB  - Visual input is ambiguous, yet conscious experience is unambiguous. In binocular
      rivalry the two eyes receive conflicting images, but only one of them is
      consciously perceived at a time. Here we search for the neural sites of the
      competitive interactions underlying this phenomenon by testing whether neural
      pattern activity occurring before stimulus presentation can predict the initial
      dominant percept in binocular rivalry and, if so, where in the brain such
      predictive activity is found. Subjects were scanned while viewing an image of a
      face in one eye and an image of a house in the other eye with anaglyph glasses.
      The rivalrous stimulus was presented briefly for each trial, and the subject
      indicated which of the two images he or she preferentially perceived. Our results
      show that BOLD fMRI multivariate pattern activity in the fusiform face area (FFA)
      before the stimulus is presented predicts which of the two images will be
      dominant, suggesting that higher extrastriate areas, such as the FFA, are not
      only correlated with, but may also be involved in determining the initial
      dominant percept in binocular rivalry. Furthermore, by examining pattern activity
      before and after trial onset, we found that pre-trial activity in the FFA for the
      rivalrous face trials is no more similar to the post-trial activity for the non
      rivalrous face trials than to that for the non-rivalrous house trials, indicating
      a dissociation between neural pattern information, which predicts a given state
      of awareness, and mean responses, which reflect the state of awareness ultimately
      achieved.

PMID- 21952196
TI  - Strong red emission of pure Y2O3 nanoparticles from oxygen related defects.
AB  - Y(2)O(3) nanoparticles with strong red luminescence (quantum yield about 25%) was
      synthesized via simple hydroxylation of yttrium nitrate using
      hexamethylenetetramine as an additive; the red luminescence is emitted from
      oxygen-related defects of pure Y(2)O(3) nanoparticles, and is tunable by altering
      the additive.

PMID- 21952197
TI  - H-reflex, muscle voluntary activation level, and fatigue index of flexor carpi
      radialis in individuals with incomplete cervical cord injury.
AB  - BACKGROUND: Individuals with incomplete spinal cord injury (SCI) are predisposed
      to muscle fatigue during voluntary exercise. However, the origin of fatigue is
      unclear. OBJECTIVE: The authors examined the motoneuron excitability, muscle
      activation level, and fatigue properties of the flexor carpi radialis muscle,
      just below the level of injury. METHODS: Nine individuals with chronic,
      incomplete cervical cord injury and 9 age-matched healthy individuals were
      recruited. The authors tested maximum voluntary contraction (MVC), motoneuron
      excitability by the maximum amplitude of the H-reflex (Hmax at C-7), and muscle
      voluntary activation level measured by the interpolated twitch technique.
      Subjects were fatigued by repetitive maximal voluntary isometric wrist flexion.
      General fatigue index (GFI), central fatigue index (CFI), and peripheral fatigue
      index (PFI) of flexor carpi radialis were examined before, during, and
      immediately after exercise. RESULTS: The Hmax in the SCI group was significantly
      higher (P = .0028) than in controls. The MVC (P < .001) and voluntary activation
      level (P = .016) in the SCI group were significantly lower. The GFI and CFI
      decreased in both the SCI and the non-SCI groups. The PFI in the SCI group was
      significantly higher (ie, less fatigue) than that in controls at 30 repetitive
      contractions. CONCLUSIONS: In individuals with incomplete SCI, the deficit in
      central drive is an important source of muscle weakness and fatigue in the muscle
      below the level of injury.

PMID- 21952198
TI  - Increase in sensorimotor cortex response to somatosensory stimulation over
      subacute poststroke period correlates with motor recovery in hemiparetic
      patients.
AB  - BACKGROUND: . Somatosensory input to the motor cortex may play a critical role in
      motor relearning after hemiparetic stroke. OBJECTIVE: . The authors tested the
      hypothesis that motor recovery after hemiparetic stroke relates to changes in
      responsiveness of the sensorimotor cortex (SMC) to somatosensory input. METHODS:
      . A total of 10 hemiparetic stroke patients underwent serial functional magnetic
      resonance imaging (fMRI) during tactile stimulation and testing of sensorimotor
      function over 1 year-at early subacute, late subacute, and chronic poststroke
      time points. RESULTS: . Over the subacute poststroke period, increased
      responsiveness of the ipsilesional SMC to tactile stimulation of a stroke
      affected digit correlated strongly with concurrent gains in motor function.
      Increased responsiveness of the ipsilesional and contralesional SMC over the
      subacute period also correlated strongly with motor recovery experienced over the
      first year poststroke. CONCLUSIONS: . These findings suggest that increased
      responsiveness of the SMC to somatosensory stimulation over the subacute
      poststroke period may contribute to motor recovery.

PMID- 21952200
TI  - Beta-arrestin2 as a competitor for GRK2 interaction with the GLP-1 receptor upon
      receptor activation.
AB  - The signaling of seven transmembrane receptors/G-protein- coupled receptors
      (GPCRs) is regulated by a number of receptor interacting proteins, including
      betaarrestins (betaarrs) and GPCR kinases (GRKs). In the present report, we have
      analyzed the interaction pattern between the glucagon-like peptide-1 (GLP-1)
      receptor (GLP-1R), betaarr2, and GRK2 using bioluminescence resonance energy
      transfer assays. We found that betaarr2 interacts with the GLP-1R in a biphasic
      manner with a phosphorylation-independent and a phosphorylation-dependent
      component. In competition experiments, we observed betaarr2 competing with GRK2
      for interaction with GLP-1R. We propose a model were betaarr2 competes with GRK2
      for interaction with the activated and GRK phosphorylated GLP-1R, suggesting a
      new role of betaarr2 in regulating the orchestration of GRK2 functionality.

PMID- 21952201
TI  - A self-assembled helical anthracene nanofibre whose P- and M-isomers show unequal
      linear dichroism in a vortex.
AB  - An anthracene derivative, having benzamide substituents bearing optically active
      alkyl chains, in hexane forms one-handedly biased helical supramolecular
      nanofibres, which show unequal linear dichroism (LD) in right- and left-handed
      vortex flows.

PMID- 21952202
TI  - Photoreactive gold(I) macrocycles with diphosphine and trans,trans-muconate
      ligands.
AB  - A pair of trans,trans-muconate ligands have been successfully aligned in two
      novel Au(I) macrocycles by design from phosphino metal precursors that undergo
      photochemical cycloaddition reactions quantitatively, resulting in the formation
      of cyclooctadiene derivatives.

PMID- 21952203
TI  - Remote-conditioning ischemia provides a potential approach to mitigate contrast
      medium-induced reduction in kidney function: a retrospective observational cohort
      study.
AB  - Contrast medium administration during imaging and therapeutic procedures can
      cause renal injury, partly due to ischemia. Therefore, we hypothesized that brief
      ischemia and reperfusion episodes applied at a distant site - multiple balloon
      inflations and deflations during angioplasty - may serve as a remote-conditioning
      (RC) stimulus and thereby protect against contrast-induced kidney injury. To test
      this hypothesis, we (1) utilized cases from a prior study in which patients
      undergoing emergent angioplasty for ST segment elevation myocardial infarction
      received either 1-3 balloon inflations (controls) or were 'conditioned' with
      multiple (>=4) inflations, and (2) assessed renal function for 3 days in patients
      with an estimated glomerular filtration rate (eGFR) of <90 ml/min/1.73 m(2) prior
      to revascularization (mild kidney disease). Both groups displayed increased eGFR
      at day 1 after angioplasty versus baseline; attributed to in-hospital hydration
      (control: 77 +/- 14 vs. 68 +/- 12 ml/min/1.73 m(2); p < 0.01; RC: 81 +/- 21 vs.
      69 +/- 12 ml/min/1.73 m(2); p < 0.01). In controls, this improvement was
      transient: eGFR subsequently decreased to 70 +/- 14 ml/min/1.73 m(2) at day 3 (p
      < 0.05). In contrast, the RC group (despite receiving 25% more contrast volume)
      showed no functional decline at day 3 (80 +/- 14 ml/min/1.73 m(2)). These results
      are consistent with remote ischemic conditioning providing a novel potential
      approach to attenuate contrast-associated renal injury.

PMID- 21952204
TI  - Initiation of chromosomal DNA replication in eukaryotic cells; contribution of
      yeast genetics to the elucidation.
AB  - Chromosomal DNA replication is a fundamental process in the transmission of
      genetic information through generations. While the molecular mechanism of DNA
      replication has been studied for a long time, knowledge regarding this process in
      eukaryotic cells has advanced rapidly in the past 20 years. Yeast genetics
      contributed profoundly to this rapid advancement. Reverse genetics and genetic
      screenings identified all genes encoding replication proteins in budding yeast.
      Moreover, the genetic interactions that were used in screenings and analyses
      provided an insight into the molecular mechanism of chromosomal DNA replication.
      Further studies showed that complicated but sophisticated mechanisms govern
      chromosomal DNA replication. The retrospective view of the genetic approaches
      used to elucidate DNA replication in eukaryotes, together with current knowledge,
      tell us the reasons why some of the genetic screenings are successful, and also
      provide ideas for future directions.

PMID- 21952205
TI  - trans-translation-mediated tight regulation of the expression of the alternative
      ribosome-rescue factor ArfA in Escherichia coli.
AB  - Ribosomes translating mRNA without an in-frame stop codon (non-stop mRNA) stall
      at its 3' end. In eubacteria, such ribosomes are rescued by SsrA-mediated trans
      translation. Recently, we have shown that Escherichia coli ArfA (formerly YhdL)
      also rescues stalled ribosomes by a mechanism distinct from that of trans
      translation. Synthetic lethality phenotype of ssrA arfA double mutants suggests
      that accumulation of stalled ribosomes is deleterious to E. coli cells. In this
      report, we show that the expression of ArfA is tightly regulated by the system
      involving trans-translation. Both premature transcription termination and
      specific cleavage by RNase III were programmed at the specific sites within the
      arfA open reading frame (ORF) and produced arfA non-stop mRNA. C-terminally
      truncated ArfA protein synthesized from arfA non-stop mRNA was tagged through
      SsrA-mediated trans-translation and degraded in wild type cell. In the absence of
      SsrA, however, C-terminally truncated ArfA escaped from degradation and had a
      function to rescue stalled ribosomes. Full-length ArfA produced only when arfA
      mRNA escapes from both premature transcription termination and RNase III cleavage
      was unstable. From these results, we illustrate a regulatory model in which ArfA
      is expressed only when it is needed, namely, when the ribosome rescue activity of
      trans-translation system is insufficient to support cell viability. This
      sophisticated regulatory mechanism suggests that the ArfA-mediated ribosome
      rescue is a backup system for trans-translation.

PMID- 21952206
TI  - Individual chromosome assignment and chromosomal collinearity in Gossypium
      thurberi, G. trilobum and D subgenome of G. barbadense revealed by BAC-FISH.
AB  - The experiment on individual chromosome assignments and chromosomal diversity was
      conducted using a multi-probe fluorescence in situ hybridization (FISH) system in
      D subgenome of tetraploid Gossypium barbadense (D(b)), G. thurberi (D(1)) and G.
      trilobum (D(8)), which the later two were the possible subgenome donors of
      tetraploid cottons. The FISH probes contained a set of bacterial artificial
      chromosome (BAC) clones specific to 13 individual chromosomes from D subgenome of
      G. hirsutum (D(h)), a D genome centromere-specific BAC clone 150D24, 45S and 5S
      ribosomal DNA (rDNA) clones, respectively. All tested chromosome orientations
      were confirmed by the centromere-specific BAC probe. In D(1) and D(8), four 45S
      rDNA loci were found assigning at the end of the short arm of chromosomes 03, 07,
      09 and 11, while one 5S rDNA locus was successfully marked at pericentromeric
      region of the short arm of chromosome 09. In D(b), three 45S rDNA loci and two 5S
      rDNA loci were found out. Among them, two 45S rDNA loci were located at the
      terminal of the short arm of chromosomes D(b)07 and D(b)09, whilst one 5S rDNA
      locus was found situating near centromeric region of the short arm of chromosome
      D(b)09. The positions of the BAC clones specific to the 13 individual chromosomes
      from D(h) were compared between D(1), D(8) and D(b). The result showed the
      existence of chromosomal collinearity within D(1) and D(8), and as well between
      them and D(b). The results will serve as a base for understanding chromosome
      structure of cotton and polyploidy evolution of cotton genome and will provide
      bio-information for assembling the sequences of finished and the on-going cotton
      whole genome sequencing projects.

PMID- 21952208
TI  - Identification of a large deletion in the first intron of the Vrn-D1 locus,
      associated with loss of vernalization requirement in wild wheat progenitor
      Aegilops tauschii Coss.
AB  - Vernalization promotes flowering in winter wheat cultivars, whereas spring wheat
      cultivars are able to transition from vegetative to reproductive phase without
      vernalization. The wheat vernalization requirement is mainly controlled by the
      major locus Vrn-1, an APETALA1/FRUITFULL MADS-box gene homolog. To study natural
      variation of the vernalization requirement in a wild progenitor of common wheat,
      we sequenced the Vrn-D(t)1 locus in four accessions of Aegilops tauschii Coss.
      Some structural mutations were found in the promoter and first intron regions of
      Vrn-D(t)1, and haplotype analysis was conducted to examine the distribution of
      each identified mutation within 211 accessions of Ae. tauschii germplasm. Out of
      the total, nine accessions, which were originally collected in Afghanistan and
      Pakistan, contained deletions of a 5.4-kb sequence in the critical region of the
      Vrn-D(t)1 first intron. The 5.4-kb deletion mutation appeared independently of
      the dominant allele of the common wheat Vrn-D1 locus. The large deletion was
      absolutely associated with a lack of vernalization requirement for flowering
      under long-day conditions, but had no influence on heading date under field
      growth conditions. The levels of Vrn-1 and WFT transcript increased in the Ae.
      tauschii accessions having the large deletion. Identification of natural mutant
      accessions with a loss of vernalization requirement indicates the agricultural
      significance of Ae. tauschii as a genetic resource for wheat breeding.

PMID- 21952207
TI  - Heading date 1 (Hd1), an ortholog of Arabidopsis CONSTANS, is a possible target
      of human selection during domestication to diversify flowering times of
      cultivated rice.
AB  - During the domestication of rice (Oryza sativa L.), diversification of flowering
      time was important in expanding the areas of cultivation. Rice is a facultative
      short day (SD) plant and requires certain periods of dark to induce flowering.
      Heading date 1 (Hd1), a regulator of the florigen gene Hd3a, is one of the main
      factors used to generate diversity in flowering. Loss-of-function alleles of Hd1
      are common in cultivated rice and cause the diversity of flowering time. However,
      it is unclear how these functional nucleotide polymorphisms of Hd1 accumulated in
      the course of evolution. Nucleotide polymorphisms within Hd1 and Hd3a were
      analyzed in 38 accessions of ancestral wild rice Oryza rufipogon and compared
      with those of cultivated rice. In contrast to cultivated rice, no nucleotide
      changes affecting Hd1 function were found in 38 accessions of wild rice
      ancestors. No functional changes were found in Hd3a in either cultivated or
      ancestral rice. A phylogenetic analysis indicated that evolution of the Hd1
      alleles may have occurred independently in cultivars descended from various
      accessions of ancestral rice. The non-functional Hd1 alleles found in cultivated
      rice may be selected during domestication, because they were not found or very
      rare in wild ancestral rice. In contrast with Hd3a, which has been highly
      conserved, Hd1 may have undergone human selection to diversify the flowering
      times of rice during domestication or the early stage of the cultivation period.

PMID- 21952209
TI  - Mining of EST-SSR markers in clam Meretrix meretrix larvae from 454 shotgun
      transcriptome.
AB  - A total of 2,970 EST-SSRs (2.38%) were identified by transcriptome sequencing of
      clam Meretrix meretrix (751,970 reads, ~310.82 Mbp), using 454 Genome Sequencer
      FLX next-generation sequencing platform. Dinucleotide SSR was the dominant repeat
      type (40.2%), followed by trinucleotide (37.8%), tetranuleotide (12.0%) and
      pentanucleotide (2.0%) SSR. The dominant repeat motif was AT (71.3%) in the
      dinucleotide SSR type and AAC (45.6%) in the trinucleotide SSR type. Nearly 79%
      of all microsatellites had flanking sequences suitable for PCR primer design.
      Half of PAL were found to be polymorphic in a subset of 40 primer pairs randomly
      selected. Specifically, the density of dinucleotide, trinucleotide and
      tetranucleotide repeats showed significant variation among four development
      stages (trochophore, D-veliger, pediveliger and postlarva). The results suggested
      that dinucleotide, trinucleotide and tetranucleotide SSRs may play an important
      role in contributing to the different expression profiles in larval stages.

PMID- 21952210
TI  - On an approximate formula for the distribution of 2-locus 2-allele model with
      mutual mutations.
AB  - An asymptotic approximation of the density function of 2-locus 2-allele model
      with mutual neutral mutations was obtained invoking the small disturbance
      asymptotic theory. It was shown by comparing the approximate formula with
      simulations that this asymptotic method gives a good approximation over the whole
      time evolution when the mutation rates are high, though it does not give good
      approximations near the stationary state when the mutation rates are low. On the
      stationary state, the squared standard linkage deviation made up by using the
      approximate formula was compared with the exact one obtained by Ohta and Kimura
      (1969b). It gave a good approximation when the recombination rate is high, even
      under low mutation rates. Furthermore, as an application of the asymptotic
      method, The Ancestral Recombination Graph (ARG) was considered.

PMID- 21952211
TI  - Examination of transpositional activity of nDart1 at different stages of rice
      development.
AB  - As a useful tool to elucidate gene functions, a rice transposon tagging line has
      been developed using an active endogenous DNA transposon, nDart1. It was highly
      desirable to evaluate the transposition timing and frequency of the nDart1
      elements during rice development to facilitate the generation of an efficient
      mutant isolation system. Comparison of the detected new insertions at different
      stages of rice development by transposon display analysis demonstrated that the
      last heading tiller carry a higher number of nDart1 elements than the main culm.
      Moreover, it was revealed that the last heading tiller could produce progeny that
      carried more new insertions of nDart1 elements, mainly as a result of the
      accumulation of somatic insertions in the parental plant. This report
      demonstrates that late tillers increase the probability of producing independent
      mutant lines.

PMID- 21952212
TI  - Platinum supported on CeO2 effectively scavenges free radicals within the
      electrolyte of an operating fuel cell.
AB  - CeO(2), Pt/CeO(2) and MnO(2) additives were found to lower the rate of free
      radical induced polymer electrolyte membrane degradation in an operating fuel
      cell by over one order of magnitude.

PMID- 21952213
TI  - Reduction in average fluoroscopic exposure times for interventional spinal
      procedures through the use of pulsed and low-dose image settings.
AB  - OBJECTIVE: A practice improvement project was completed with the goal of reducing
      radiation exposure times in a busy spinal intervention practice through the use
      of "pulsed" and "low-dose fluoroscopy." The goal was to quantify the reduction in
      fluoroscopy exposure times with these modes. DESIGN: Exposure times were recorded
      for 316 patients undergoing spinal interventional procedures before and after the
      implementation of this project. Before implementation, 158 consecutive patients
      received spinal interventions with nonpulsed fluoroscopy on an Orthopedic
      Equipment Company 9800 and exposure times were recorded. After implementation of
      the practice improvement project, 158 consecutive patients received spinal
      interventions with pulsed and low-dose modes. Exposure times were then compared
      between these groups. RESULTS: Pulsed and low-dose fluoroscopy modes reduced
      overall exposure times by 56.7% after implementation of the practice improvement
      project. CONCLUSIONS: The use of pulsed and low-dose fluoroscopy in addition to
      lead shielding; increasing distance from the radiation source; collimation;
      limited use of magnification, boost, or digital subtraction; and proficiency with
      interventional techniques should be used to reduce radiation exposure in
      concordance with the principle of "as low as reasonably achievable."

PMID- 21952214
TI  - Dysphagia associated with unilateral vocal cord immobility after cardiovascular
      surgery.
AB  - OBJECTIVE: Dysphagia associated with unilateral vocal cord immobility (UVCI) has
      received much less attention than did voice and phonation. The aim of this
      descriptive study was to evaluate the outcome of dysphagia associated with UVCI.
      DESIGN: Between June 2006 and September 2009, 69 hospitalized patients who
      underwent cardiovascular surgery were referred for dysphagia. Video endoscopic
      evaluation of swallowing was used for the detection of swallowing difficulties.
      Severity of dysphagia was assessed using the Dysphagia Severity Scale. RESULTS:
      Among the 69 patients, 31 UVCI patients who underwent video endoscopic evaluation
      of swallowing at least twice were used for analysis. All patients had severe to
      mild dysphagia at the first evaluation. Nineteen patients recovered from the UVCI
      at a mean follow-up of 125 days, whereas 12 had persistent UVCI at a mean follow
      up of 216 days. Dysphagia Severity Scale at the first evaluation was not
      significantly different in both groups. At the last follow-up, the Dysphagia
      Severity Scale improved considerably without a significant difference in the
      magnitude of improvement in both groups. In the recovered and persistent UVCI
      groups, 16 and 7 patients, respectively, resumed their regular diets.
      CONCLUSIONS: Dysphagia associated with UVCI after surgery recovers, irrespective
      of the functional results of the UVCI.

PMID- 21952215
TI  - Robot-assisted exercise for hand weakness after stroke: a pilot study.
AB  - OBJECTIVE: Upper-limb paresis is a major source of disability in stroke
      survivors, and robotic device-aided exercise therapy is a promising approach to
      enhance motor abilities. Few robotic devices have been available to provide
      therapy to the fingers and hand. This study was designed to test a new robotic
      device for hand rehabilitation in stroke survivors. DESIGN: This is an open-label
      pilot study of 12 individuals with chronic moderate hemiparesis after stroke.
      Participants underwent a 6-wk training program using a hand robotic device.
      Participants received a total of 18 hrs of robotic therapy. RESULTS: Improvements
      were found in multiple measures of motor performance, including the Upper
      Extremity Fugl-Meyer test, the Motor Activity Log, the Manual Ability Measure-36,
      and the Jebsen Hand Function Test. All subjects tolerated the treatment well and
      no complications were observed. CONCLUSIONS: Robotic therapy for hand paresis
      after stroke is safe and feasible, and further studies of efficacy are justified
      by these preliminary results.

PMID- 21952216
TI  - Room temperature magnetic materials from nanostructured diblock copolymers.
AB  - Nanostructured magnetic materials are important for many advanced applications.
      Consequently, new methods for their fabrication are critical. However, coupling
      self-assembly to the generation of magnetic materials in a simple, straight
      forward manner has remained elusive. Although several approaches have been
      considered, most have multiple processing steps, thus diminishing their use of
      self-assembly to influence magnetic properties. Here we develop novel block
      copolymers that are preprogrammed with the necessary chemical information to
      microphase separate and deliver room temperature ferromagnetic properties
      following a simple heat treatment. The importance of the nanostructured
      confinement is demonstrated by comparison with the parent homopolymer, which
      provides only paramagnetic materials, even though it is chemically identical and
      has a higher loading of the magnetic precursor. In addition to the room
      temperature ferromagnetic properties originating from the block copolymer, the in
      situ generation densely functionalizes the surface of the magnetic elements,
      rendering them oxidatively stable.

PMID- 21952217
TI  - Identification and microbial production of a terpene-based advanced biofuel.
AB  - Rising petroleum costs, trade imbalances and environmental concerns have
      stimulated efforts to advance the microbial production of fuels from
      lignocellulosic biomass. Here we identify a novel biosynthetic alternative to D2
      diesel fuel, bisabolane, and engineer microbial platforms for the production of
      its immediate precursor, bisabolene. First, we identify bisabolane as an
      alternative to D2 diesel by measuring the fuel properties of chemically
      hydrogenated commercial bisabolene. Then, via a combination of enzyme screening
      and metabolic engineering, we obtain a more than tenfold increase in bisabolene
      titers in Escherichia coli to >900 mg l(-1). We produce bisabolene in
      Saccharomyces cerevisiae (>900 mg l(-1)), a widely used platform for the
      production of ethanol. Finally, we chemically hydrogenate biosynthetic bisabolene
      into bisabolane. This work presents a framework for the identification of novel
      terpene-based advanced biofuels and the rapid engineering of microbial farnesyl
      diphosphate-overproducing platforms for the production of biofuels.

PMID- 21952218
TI  - A shift of the TOR adaptor from Rictor towards Raptor by semaphorin in C.
      elegans.
AB  - The target of rapamycin (TOR), a central regulator for cell growth and
      metabolism, resides in the two functionally distinct complexes TORC1 and TORC2,
      which are defined by their adaptors Raptor and Rictor, respectively. How the
      formation of the two TORCs is orchestrated remains unclear. Here we show the
      control of TOR partnering by semaphorin-plexin signalling in Caenorhabditis
      elegans. In semaphorin and plexin mutants, TOR-Raptor association decreases
      whereas TOR-Rictor association increases, concomitantly with TORC1 down- and
      TORC2 up-regulation. Epidermal defects in the mutants are suppressed by
      inhibiting TORC2 or reinforcing TORC1 signalling. Conversely, inhibition of TORC1
      signalling phenocopies the mutants. Thus, our results indicate that TORC
      formation is a singularly important step in semaphorin signalling that culminates
      in diverse outcomes including TORC1-promoted messenger RNA translation and TORC2
      regulated cytoskeletal remodelling.

PMID- 21952219
TI  - The collagen-binding protein of Streptococcus mutans is involved in haemorrhagic
      stroke.
AB  - Although several risk factors for stroke have been identified, one-third remain
      unexplained. Here we show that infection with Streptococcus mutans expressing
      collagen-binding protein (CBP) is a potential risk factor for haemorrhagic
      stroke. Infection with serotype k S. mutans, but not a standard strain,
      aggravates cerebral haemorrhage in mice. Serotype k S. mutans accumulates in the
      damaged, but not the contralateral hemisphere, indicating an interaction of
      bacteria with injured blood vessels. The most important factor for high-virulence
      is expression of CBP, which is a common property of most serotype k strains. The
      detection frequency of CBP-expressing S. mutans in haemorrhagic stroke patients
      is significantly higher than in control subjects. Strains isolated from
      haemorrhagic stroke patients aggravate haemorrhage in a mouse model, indicating
      that they are haemorrhagic stroke-associated. Administration of recombinant CBP
      causes aggravation of haemorrhage. Our data suggest that CBP of S. mutans is
      directly involved in haemorrhagic stroke.

PMID- 21952220
TI  - Role of mid-gap states in charge transport and photoconductivity in semiconductor
      nanocrystal films.
AB  - Colloidal semiconductor nanocrystals have attracted significant interest for
      applications in solution-processable devices such as light-emitting diodes and
      solar cells. However, a poor understanding of charge transport in nanocrystal
      assemblies, specifically the relation between electrical conductance in dark and
      under light illumination, hinders their technological applicability. Here we
      simultaneously address the issues of 'dark' transport and photoconductivity in
      films of PbS nanocrystals, by incorporating them into optical field-effect
      transistors in which the channel conductance is controlled by both gate voltage
      and incident radiation. Spectrally resolved photoresponses of these devices
      reveal a weakly conductive mid-gap band that is responsible for charge transport
      in dark. The mechanism for conductance, however, changes under illumination when
      it becomes dominated by band-edge quantized states. In this case, the mid-gap
      band still has an important role as its occupancy (tuned by the gate voltage)
      controls the dynamics of band-edge charges.

PMID- 21952221
TI  - Capturing the essence of folding and functions of biomolecules using coarse
      grained models.
AB  - The distances over which biological molecules and their complexes can function
      range from a few nanometres, in the case of folded structures, to millimetres,
      for example, during chromosome organization. Describing phenomena that cover such
      diverse length, and also time, scales requires models that capture the underlying
      physics for the particular length scale of interest. Theoretical ideas, in
      particular, concepts from polymer physics, have guided the development of coarse
      grained models to study folding of DNA, RNA and proteins. More recently, such
      models and their variants have been applied to the functions of biological
      nanomachines. Simulations using coarse-grained models are now poised to address a
      wide range of problems in biology.

PMID- 21952222
TI  - Effects of a small acute subdural hematoma following traumatic brain injury on
      neuromonitoring, brain swelling and histology in pigs.
AB  - An acute subdural hematoma (ASDH) induces pathomechanisms which worsen outcome
      after traumatic brain injury, even after a small hemorrhage. Synergistic effects
      of a small ASDH on brain damage are poorly understood, and were studied here
      using neuromonitoring for 10 h in an injury model of controlled cortical impact
      (CCI) and ASDH. Pigs (n = 32) were assigned to 4 groups: sham, CCI (2.5 m/s),
      ASDH (2 ml) and CCI + ASDH. Intracranial pressure was significantly increased
      above sham levels by all injuries with no difference between groups. CCI and ASDH
      reduced ptiO(2) by a maximum of 36 +/- 9 and 26 +/- 11%, respectively. The
      combination caused a 31 +/- 11% drop. ASDH alone and in combination with CCI
      caused a significant elevation in extracellular glutamate, which remained
      increased longer for CCI + ASDH. The same two groups had significantly higher
      peak lactate levels compared to sham. Somatosensory evoked potential (SSEP)
      amplitude was persistently reduced by combined injury. These effects translated
      into significantly elevated brain water content and histological damage in all
      injury groups. Thus, combined injury had stronger effects on glutamate and SSEP
      when compared to CCI and ASDH, but no clear-cut synergistic effects of 2 ml ASDH
      on trauma were observed. We speculate that this was partially due to the CCI
      injury severity.

PMID- 21952224
TI  - Gender differences in sociodemographic and behavioral influences of physical
      activity in Mexican-origin adolescents.
AB  - BACKGROUND: Understanding the factors that contribute to physical activity (PA)
      in Mexican-origin adolescents is essential to the design of effective efforts to
      enhance PA participation in this population. METHODS: Multivariable logistic
      regression was used to identify sociodemographic and behavioral correlates of
      self-reported PA in school and community settings in 1154 Mexican-origin
      adolescents aged 12-17 years in Houston, TX. RESULTS: The majority of adolescents
      were born in the US (74%), approximately half (51%) were overweight or obese, and
      nearly three-quarters (73%) watched more than 2 hours of weekday television.
      Similarities and differences by setting and gender were observed in the
      relationships between sociodemographic and behavioral characteristics and PA. In
      boys, parental education and attending physical education (PE) were positively
      associated with PA across multiple PA outcomes. Adolescent linguistic
      acculturation was inversely associated with participation in community sports,
      whereas parental linguistic acculturation was positively associated with PA at
      school. In girls, PA in school and community settings was inversely associated
      with TV viewing and positively associated with PE participation. CONCLUSIONS:
      These findings highlight similarities and differences in correlates of PA among
      boys and girls, and point toward potential sources of opportunities as well as
      disparities for PA behaviors in Mexican-origin adolescents.

PMID- 21952225
TI  - Effects of hydrogen sulfide synthesis inhibitors on posthypoxic ventilatory
      behavior in the C57BL/6J mouse.
AB  - BACKGROUND: H(2)S synthesis inhibitors (HSSI) have been shown to impact
      respiratory control. For instance, the HSSI hydroxylamine (HA) decreases the
      respiratory discharge rate from isolated medullary sections, and HA in addition
      to other HSSIs propargylglycine and amino-oxyacetic acid (AOAA) have been found
      to reduce hypoxic responsiveness. OBJECTIVES: The aim of this study was to
      determine if administration of HSSIs could improve respiratory stability in an
      intact organism prone to recurrent central apneas. METHODS: Saline and HSSI
      compounds were administered to C57BL/6J mice (n = 24), a strain predisposed to
      recurrent central apneas, prior to measurement of hypoxic and posthypoxic
      ventilatory behavior. RESULTS: Administration of HA and AOAA resulted in a
      significantly smaller percentage of animals expressing one or more apneas during
      reoxygenation compared to saline control, and animals given AOAA demonstrated a
      smaller coefficient of variation for frequency during reoxygenation, a marker
      suggesting greater respiratory stability. This occurred despite varying effects
      of the three HSSI compounds on hypoxic ventilatory response. CONCLUSIONS:
      Instability and pause expression are improved by targeting H(2)S synthesis, an
      effect not predicted by effects on hypoxic responsiveness.

PMID- 21952226
TI  - Cobalt(II), nickel(II) and copper(II) complexes of a hexadentate pyridine amide
      ligand. Effect of donor atom (ether vs. thioether) on coordination geometry, spin
      state of cobalt and M(III)-M(II) redox potential.
AB  - Using an acyclic hexadentate pyridine amide ligand, containing a -OCH(2)CH(2)O-
      spacer between two pyridine-2-carboxamide units (1,4-bis[o-(pyrydine-2
      carboxamidophenyl)]-1,4-dioxabutane (H(2)L(9)), in its deprotonated form), four
      new complexes, [Co(II)(L(9))] (1) and its one-electron oxidized counterpart
      [Co(III)(L(9))][NO(3)].2H(2)O (2), [Ni(II)(L(9))] (3) and [Cu(II)(L(9))] (4),
      have been synthesized. Structural analyses revealed that the Co(II) centre in 1
      and the Ni(II) centre in 3 are six-coordinate, utilizing all the available donor
      sites and the Cu(II) centre in 4 is effectively five-coordinated (one of the
      ether O atoms does not participate in coordination). The structural parameters
      associated with the change in the metal coordination environment have been
      compared with corresponding complexes of thioether-containing hexadentate
      ligands. The MU(eff) values at 298 K of 1-4 correspond to S = 3/2, S = 0, S = 1
      and S = 1/2, respectively. Absorption spectra for all the complexes have been
      investigated. EPR spectral properties of the copper(II) complex 4 have been
      investigated, simulated and analyzed. Cyclic voltammetric experiments in
      CH(2)Cl(2) reveal quasireversible Co(III)-Co(II), Ni(III)-Ni(II) and Cu(II)-Cu(I)
      redox processes. In going from ether O to thioether S coordination, the effect of
      the metal coordination environment on the redox potential values of Co(III)
      Co(II) (here the effect of spin-state as well), Ni(III)-Ni(II) and Cu(II)-Cu(I)
      processes have been systematically analyzed.

PMID- 21952227
TI  - Water and aqueous solutions: simple non-speculative model approach.
AB  - Different ways of molecular modeling of water are analyzed and their similarities
      and differences identified. An up-to-date summary of achievements of a general
      approach to common rigid site-site interaction models of molecular fluids applied
      to water and aqueous solutions is then presented and discussed. The method is
      based on considering only a short-range part of a total realistic potential (such
      as SPC/E or TIPxP) which determines the structure of water (and fluids in
      general). A simplification of the interactions at short intermolecular
      separations leads then to simple models, called primitive models. Quite accurate
      results in an analytic form for the thermodynamic properties of the models are
      obtained using the thermodynamic perturbation theory. It is shown that the
      properly constructed primitive models reproduce, qualitatively, anomalies of pure
      water and basic characteristics of hydrophobic hydration. The concept of an
      extended excluded volume, based on pseudo-hard bodies, is introduced and
      exemplified by considering the partial molar volume of apolar solutes. Potential
      future development towards a theory of water based on the primitive models as a
      reference with the long-range contributions added as a perturbation is discussed.

PMID- 21952228
TI  - Photocatalytic water oxidation on F, N co-doped TiO2 with dominant exposed {001}
      facets under visible light.
AB  - Visible-light-responsive anatase TiO(2) platelets with dominant {001} facets were
      prepared via a facile nitridation reaction from a TiOF(2) precursor. The in situ
      co-doping of N and F in the anatase TiO(2) nanoparticles leads to drastically
      enhanced absorption and excellent water oxidation performance in the visible
      light region.

PMID- 21952231
TI  - Self-stacked Co3O4 nanosheets for high-performance lithium ion batteries.
AB  - Self-stacked Co(3)O(4) nanosheets separated by carbon layers were synthesized via
      a facile method. They exhibit excellent electrochemical performance that results
      from superior electronic conductivity endowed by carbon, a reduced Li(+)
      diffusion length within the building blocks and a large electrode/electrolyte
      contact area due to the interspaces between the blocks.

PMID- 21952229
TI  - Chronic social stress induces cardiomyocyte contractile dysfunction and
      intracellular Ca2+ derangement in rats.
AB  - Chronic psychosocial stress triggers cardiovascular diseases although underlying
      mechanisms are still elusive. This study examined the effect of social stress on
      cardiomyocyte contractile function and pathological changes in myocardium using
      the visible burrow system (VBS) model. Chronic social stress was induced using a
      mixed-sex VBS housing in adult Sprague-Dawley (SD) rats. Contractile and
      intracellular Ca(2+) properties were evaluated in isolated cardiomyocytes
      including peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening
      (TR(90)), maximal velocity of shortening/relengthening (+/- dL/dt), Fura-2
      fluorescence intensity, and intracellular Ca(2+) decay. Myocardial histology was
      evaluated using Masson trichrome staining. Social stress led to depressed PS, +/-
      dL/dt, shortened TPS and prolonged TR(90) compared with the unstressed controls.
      Baseline and electrically-stimulated rise in Ca(2+) were reduced whereas
      intracellular Ca(2+) decay was delayed in stressed rats. Histological analyses
      exhibited overt interstitial fibrosis and cardiomyocyte hypertrophy in stressed
      rats. The GSH/GSSG ratio (indicative of oxidative stress status) was reduced
      whereas oxidative protein carbonyl formation was elevated in stressed rats.
      Western blot analysis showed unchanged expression of superoxide dismutase 1
      (SOD1), beta(1)-adrenoceptor (beta(1)-AR) levels, reduced sarco(endo)plasmic
      reticulum Ca(2+)-ATPase (SERCA2a) levels, and elevated phosphorylation of the
      stress signaling protein kinase JNK but not ERK in myocardium from stressed rats.
      Short-term in vitro treatment of cardiomyocytes with the stress inducer
      phenylephrine mimicked cell damage and intracellular Ca(2+) mishandling, the
      effects of which were mitigated by antioxidant, JNK inhibition, carvedilol and
      SERCA2a adenovirus. These findings indicate that chronic social stress is
      detrimental to cardiac structure and function possibly via mechanisms associated
      with oxidative injury and intracellular Ca(2+) mishandling.

PMID- 21952233
TI  - Physical examination and electrocardiographic findings in young subjects--are
      they predictive of echocardiographic findings?

PMID- 21952235
TI  - Sirt1 is a regulator of bone mass and a repressor of Sost encoding for
      sclerostin, a bone formation inhibitor.
AB  - Sirt1, the mammalian ortholog of the yeast Sir2 (silent information regulator 2),
      was shown to play an important role in metabolism and in age-associated diseases,
      but its role in skeletal homeostasis and osteoporosis has yet not been studied.
      Using 129/Sv mice with a germline mutation in the Sirt1 gene, we demonstrate that
      Sirt1 haplo-insufficient (Sirt1(+/-)) female mice exhibit a significant reduction
      in bone mass characterized by decreased bone formation and increased marrow
      adipogenesis. Importantly, we identify Sost, encoding for sclerostin, a critical
      inhibitor of bone formation, as a novel target of Sirt1. Using chromatin
      immunoprecipitation analysis, we reveal that Sirt1 directly and negatively
      regulates Sost gene expression by deacetylating histone 3 at lysine 9 at the Sost
      promoter. Sost down-regulation by small interfering RNA and the administration of
      a sclerostin-neutralizing antibody restore gene expression of osteocalcin and
      bone sialoprotein as well as mineralized nodule formation in Sirt1(+/-) marrow
      derived mesenchymal stem cells induced to osteogenesis. These findings reveal a
      novel role for Sirt1 in bone as a regulator of bone mass and a repressor of
      sclerostin, and have potential implications suggesting that Sirt1 is a target for
      promoting bone formation as an anabolic approach for treatment of osteoporosis.

PMID- 21952234
TI  - Fetal hypothalamus-pituitary-adrenal responses to estradiol sulfate.
AB  - Estradiol (E(2)) is an important modifier of the activity of the fetal
      hypothalamus-pituitary-adrenal axis. We have reported that estradiol-3-sulfate
      (E(2)SO(4)) circulates in fetal blood in far higher concentrations than E(2) and
      that the fetal brain expresses steroid sulfatase, required for local
      deconjugation of E(2)SO(4). We performed the present study to test the hypothesis
      that chronic infusion of E(2)SO(4) chronically increases ACTH and cortisol
      secretion and that it shortens gestation. Chronically catheterized fetal sheep
      were treated with E(2)SO(4) intracerebroventricular (n = 5), E(2)SO(4) iv (n =
      4), or no steroid infusion (control group, n = 5). Fetuses were subjected to
      arterial blood sampling every other day until spontaneous birth for plasma
      hormone analysis. Treatment with E(2)SO(4) attenuated preparturient increases in
      ACTH secretion near term without affecting the ontogenetic rise in plasma
      cortisol. Infusion of E(2)SO(4) intracerebroventricularly significantly increased
      plasma E(2), plasma E(2)SO(4), and plasma progesterone and shortened gestation
      compared with all other groups. These results are consistent with the conclusion
      that E(2)SO(4): 1) interacts with the hypothalamus-pituitary-adrenal axis
      primarily by stimulating cortisol secretion and inhibiting ACTH and pro-ACTH
      secretion by negative feedback; and 2) stimulates the secretion of E(2) and
      E(2)SO(4). We conclude that the endocrine response to E(2)SO(4) in the fetus is
      not identical with the response to E(2).

PMID- 21952236
TI  - Intrinsic sexually dimorphic expression of the principal human CYP3A4 correlated
      with suboptimal activation of GH/glucocorticoid-dependent transcriptional
      pathways in men.
AB  - Cytochrome P450 (CYP)3A4 is the principal and most abundant human isoform of CYP
      responsible for the metabolism of more than 50% of all consumed drugs and
      innumerable endogenous compounds. Expression of CYP3A4 is sexually dimorphic and
      regulated by the combined actions of GH and glucocorticoids. In the case of the
      rat, nearly all of the CYPs are "intrinsically" or "inherently" sexually
      dimorphic, meaning that the expressed sex differences are permanent and
      irreversible. Using primary hepatocyte cultures derived from men and women
      exposed to physiologic-like levels of continuous GH (the feminine circulating
      profile) alone, dexamethasone alone, and the combined regimen, we observed a
      dramatic inherent CYP3A4 sexual dimorphism (women more than men) with all
      treatments. The molecular basis for this intrinsic sexually dimorphic expression
      of CYP3A4 appears to be due, at least in part, to a greater level of hormone
      dependent activation and nuclear translocation of both hepatocyte nuclear factor
      4alpha (HNF-4alpha) and pregnane X receptor in female hepatocytes. Furthermore,
      these transcription factors exhibited significantly higher DNA binding levels to
      their specific motifs on the CYP3A4 promoter in female hepatocytes, inferring a
      possible explanation for the elevated expression of CYP3A4 in women. Accordingly,
      experiments using HepG2 cells treated with small inhibitory RNA-induced knockdown
      of HNF-4alpha and/or transfected with luciferase reporter constructs containing a
      CYP3A4 promoter lacking HNF-4alpha-binding motifs demonstrated that GH, to a
      greater extent dexamethasone, and to the greatest extent the combine hormone
      regimen, stimulated HNF-4alpha and pregnane X receptor promoter transactivation,
      signifying enhanced transcription of CYP3A4 and, thus, identifying a molecular
      mechanism contributing to the intrinsic sexual dimorphic expression of human
      CYP3A4.

PMID- 21952237
TI  - Toll-like receptor-3 ligation-induced indoleamine 2, 3-dioxygenase expression in
      human trophoblasts.
AB  - Indoleamine 2,3-dioxygenase (IDO) is an enzyme that degrades an essential amino
      acid, tryptophan, and plays a role in inhibiting the proliferation of T cells and
      intracellular pathogens. Inhibiting IDO in mice leads to fetal rejection,
      suggesting its significance in establishing pregnancy. Toll-like receptor 3 (TLR
      3) is a key component of the innate immune system that recognizes viral double
      stranded RNA and triggers immune reactions by producing type I interferon. Using
      a human trophoblast cell culture system, we studied the effect of TLR-3 ligation
      on IDO expression and function by treating trophoblasts with polyinosinic
      polycytidylic acid [poly(I:C)] (a synthetic double stranded RNA, which mimics
      viral RNA). Real-time PCR and Western blot analysis revealed that IDO mRNA and
      protein expression was significantly induced by poly(I:C). The activity of IDO
      was also increased by poly(I:C) given that the L-kynurenine concentrations were
      elevated in conditioned media. Conditioned media from poly(I:C)-treated
      trophoblasts were found to inhibit the proliferation of human T cells
      significantly. Poly(I:C) was also shown to induce interferon (IFN)-beta mRNA
      expression in trophoblasts. Recombinant human IFN-beta increased IDO mRNA
      expression in trophoblasts more rapidly than poly(I:C). Pretreating with
      neutralizing antibody against IFN-beta significantly suppressed IDO induction by
      poly(I:C). Collectively we have demonstrated that ligation of TLR-3 by poly(I:C)
      induces IDO expression in human first-trimester trophoblasts via an IFN-beta
      dependent pathway. These findings suggest that upon viral infection, trophoblasts
      induce IDO and in turn contribute to antimicrobial activity and maintenance of
      fetomaternal tolerance.

PMID- 21952238
TI  - Depletion of Bhmt elevates sonic hedgehog transcript level and increases beta
      cell number in zebrafish.
AB  - Betaine homocysteine S-methyltransferase (BHMT, EC 2.1.1.5) is a key enzyme in
      the methionine cycle and is highly expressed in the liver. Despite its important
      biochemical function, it is not known whether BHMT plays a role during organ
      development. In this report, we showed that early in development of zebrafish
      before endoderm organogenesis, bhmt is first expressed in the yolk syncytial
      layer and then after liver formation becomes a liver-enriched gene. By using the
      anti-bhmt morpholinos that deplete the Bhmt, we found that in morphant embryos,
      several endoderm-derived organs, including liver, exocrine pancreas, and
      intestine are hypoplastic. Strikingly, the number of beta-cells in the pancreatic
      islet was increased rather than reduced in the morphant. Additional studies
      showed that Bhmt depletion elevates the sonic hedgehog (shh) transcript level in
      the morphant, whereas Bhmt-depletion in the Shh-deficient mutant syu failed to
      rescue the isletless phenotype. These molecular and genetic data strongly suggest
      that Shh functions downstream of Bhmt to promote beta-cell development.
      Therefore, although there are still many intriguing questions to be answered, our
      finding may identify a novel function for Bhmt involving modulation of Shh
      signaling to control beta-cell development.

PMID- 21952239
TI  - Minireview: Putting physiology back into estrogens' mechanism of action.
AB  - After decades of research, the mechanism by which estrogens stimulate the
      proliferation of epithelial cells in the endometrium and mammary gland, and in
      the carcinomas that arise in those tissues, is still not understood. Cells do not
      proliferate in response to 17beta-estradiol (E2) alone, and although it is widely
      recognized that growth factors play a role in E2's proliferative effect, exactly
      how they are involved is unclear. It has long been known that the proliferation
      of endometrial epithelial cells is preceded by dramatic increases in blood flow
      and microvascular permeability, filling the subepithelial stroma with plasma and
      the proteins it contains, such as IGF-I, which is known to synergize with E2 in
      the induction of cell proliferation. The hyperpermeability is caused by vascular
      endothelial growth factor (VEGF), which is rapidly induced by E2, via the
      transcription factors hypoxia-inducible factor 1 and estrogen receptor alpha, in
      luminal epithelial cells in vivo. As we recently showed, VEGF is also strongly
      induced in endometrial cancer cells in vitro when excessive degradation of
      hypoxia-inducible factor 1alpha, caused by the abnormally high oxygen level to
      which cultured cells are exposed, is prevented. Putting these facts together, we
      now propose a new model of E2-induced proliferation in which VEGF-induced
      vascular hyperpermeability plays an essential role. E2 first induces the
      expression by endometrial epithelial cells of VEGF, which then acts in a
      paracrine manner to induce interendothelial cell gaps in subepithelial blood
      vessels, through which plasma and the proteins therein enter the adjacent stroma.
      Plasma carries even more E2, which circulates bound to proteins, and IGF-l, which
      together drive epithelial cells completely through the cell cycle.

PMID- 21952240
TI  - Testicular somatic cells, not gonocytes, are the major source of functional
      activin A during testis morphogenesis.
AB  - Proper development of the seminiferous tubules (or testis cords in embryos) is
      critical for male fertility. Sertoli cells, somatic components of the
      seminiferous tubules, serve as nurse cells to the male germline, and thus their
      numbers decide the quantity of sperm output in adulthood. We previously
      identified activin A, the protein product of the activin betaA (Inhba) gene, as a
      key regulator of murine Sertoli cell proliferation and testis cord expansion
      during embryogenesis. Although our genetic studies implicated fetal Leydig cells
      as the primary producers of testicular activin A, gonocytes are another potential
      source. To investigate the relative contribution of gonocyte-derived activin A to
      testis morphogenesis, we compared testis development in the Inhba global knockout
      mouse, which lacks activin A production in all cells (including the gonocytes),
      and a steroidogenic factor 1 (Sf1)-specific conditional knockout model in which
      activin A expression in testicular somatic cells is disrupted but gonocyte
      expression of activin A remains intact. Surprisingly, testis development was
      comparable in these two models of activin A insufficiency, with similar
      reductions in Sertoli cell proliferation and minor differences in testis
      histology. Thus, our findings suggest activin A from male gonocytes is
      insufficient to promote Sertoli cell proliferation and testis cord expansion in
      the absence of somatic cell-derived activin A. Evaluation of adult male mice with
      fetal disruption of activin A revealed reduced testis size, lowered sperm
      production, altered testicular histology, and elevated plasma FSH levels, defects
      reminiscent of human cases of androgen-sufficient idiopathic oligozoospermia.

PMID- 21952241
TI  - Pioglitazone induces a proadipogenic antitumor response in mice with PAX8
      PPARgamma fusion protein thyroid carcinoma.
AB  - Approximately 35% of follicular thyroid carcinomas harbor a chromosomal
      translocation that results in expression of a paired box gene 8-peroxisome
      proliferator-activated receptor gamma gene (PPARgamma) fusion protein (PPFP). To
      better understand the oncogenic role of PPFP and its relationship to endogenous
      PPARgamma, we generated a transgenic mouse model that combines Cre-dependent PPFP
      expression (PPFP;Cre) with homozygous deletion of floxed Pten (PtenFF;Cre), both
      thyroid specific. Although neither PPFP;Cre nor PtenFF;Cre mice develop thyroid
      tumors, the combined PPFP;PtenFF;Cre mice develop metastatic thyroid cancer,
      consistent with patient data that PPFP is occasionally found in benign thyroid
      adenomas and that PPFP carcinomas have increased phosphorylated AKT/protein
      kinase B. We then tested the effects of the PPARgamma agonist pioglitazone in our
      mouse model. Pioglitazone had no effect on PtenFF;Cre mouse thyroids. However,
      the thyroids in pioglitazone-fed PPFP;PtenFF;Cre mice decreased 7-fold in size,
      and metastatic disease was prevented. Remarkably, pioglitazone caused an
      adipogenic response in the PPFP;PtenFF;Cre thyroids characterized by lipid
      accumulation and the induction of a broad array of adipocyte PPARgamma target
      genes. These data indicate that, in the presence of pioglitazone, PPFP has
      PPARgamma-like activity that results in trans-differentiation of thyroid
      carcinoma cells into adipocyte-like cells. Furthermore, the data predict that
      pioglitazone will be therapeutic in patients with PPFP-positive carcinomas.

PMID- 21952242
TI  - Calcium insufficiency accelerates type 1 diabetes in vitamin D receptor-deficient
      nonobese diabetic (NOD) mice.
AB  - Vitamin D exerts important regulatory effects on the endocrine and immune
      systems. Autoimmune type 1 diabetes (T1D) development in the inbred NOD mouse
      strain can be accelerated by vitamin D insufficiency or suppressed by chronic
      treatment with high levels of 1alpha,25-dihydroxyvitamin D(3). Consequently, a
      report that T1D development was unaffected in NOD mice genetically lacking the
      vitamin D receptor (VDR) was unexpected. To further assess this result, the
      mutant stock was imported to The Jackson Laboratory, backcrossed once to
      NOD/ShiLtJ, and progeny rederived through embryo transfer. VDR-deficient NOD mice
      of both sexes showed significant acceleration of T1D. This acceleration was not
      associated with alterations in immune cells targeting pancreatic beta-cells.
      Rather, the capacity of beta-cells to produce and/or secrete insulin was severely
      impaired by the hypocalcaemia developing in VDR-deficient NOD mice fed a standard
      rodent chow diet. Feeding a high-lactose calcium rescue diet that circumvents a
      VDR requirement for calcium absorption from the intestine normalized serum
      calcium levels, restored beta-cell insulin secretion, corrected glucose
      intolerance, and eliminated accelerated T1D in VDR-deficient NOD mice. These
      findings suggest that calcium and/or vitamin D supplementation may improve
      disease outcomes in some T1D-prone individuals that are calcium deficient.

PMID- 21952243
TI  - Inhibition of the protein tyrosine phosphatase SHP-1 increases glucose uptake in
      skeletal muscle cells by augmenting insulin receptor signaling and GLUT4
      expression.
AB  - The protein tyrosine phosphatase (PTPase) Src-homology 2-domain-containing
      phosphatase (SHP)-1 was recently reported to be a novel regulator of insulin's
      metabolic action. In order to examine the role of this PTPase in skeletal muscle,
      we used adenovirus (AdV)-mediated gene transfer to express an interfering mutant
      of SHP-1 [dominant negative (DN)SHP-1; mutation C453S] in L6 myocytes. Expression
      of DNSHP-1 increased insulin-induced Akt serine-threonine kinase phosphorylation
      and augmented glucose uptake and glycogen synthesis. Pharmacological inhibition
      of glucose transporter type 4 (GLUT4) activity using indinavir and GLUT4
      translocation assays revealed an important role for this transporter in the
      increased insulin-induced glucose uptake in DNSHP-1-expressing myocytes. Both
      GLUT4 mRNA and protein expression were also found to be increased by DNSHP-1
      expression. Furthermore, AdV-mediated delivery of DNSHP-1 in skeletal muscle of
      transgenic mice overexpressing Coxsackie and AdV receptor also enhanced GLUT4
      protein expression. Together, these findings confirm that SHP-1 regulates muscle
      insulin action in a cell-autonomous manner and further suggest that the PTPase
      negatively modulates insulin action through down-regulation of both insulin
      signaling to Akt and GLUT4 translocation, as well as GLUT4 expression.

PMID- 21952244
TI  - A role for metalloendopeptidases in the breakdown of the gut hormone, PYY 3-36.
AB  - Peptide YY(3-36) (PYY(3-36)) is a gut hormone that acts on Y2 receptors to reduce
      appetite. Obese humans are sensitive to the anorectic effects of PYY(3-36) and
      display a blunted postprandial rise in PYY(3-36). Bariatric surgery results in
      increased circulating PYY-immunoreactivity, which appears to play a role in
      postoperative weight loss. The utility of PYY(3-36) as an antiobesity treatment
      is limited by its short circulating half-life. Insight into the mechanisms by
      which PYY(3-36) is degraded may aid design of long-acting PYY(3-36) analogues or
      enzyme inhibitor therapies. We aimed to investigate the role of
      metalloendopeptidases in PYY(3-36) degradation and determine whether modulation
      of these enzymes enhanced PYY(3-36) plasma levels and bioactivity in vivo.
      Degradation and resultant cleavage products of PYY(3-36) were characterized after
      incubation with neprilysin and meprin beta and with a kidney brush border
      preparation in vitro. Specific metalloendopeptidase inhibitors were
      coadministered with PYY(3-36) to mice and subsequent PYY(3-36) plasma levels and
      bioactivity determined. Meprin beta cleaves PYY(3-36) at multiple conserved
      acidic sites. Blocking the actions of meprin beta prevents the degradative effect
      of kidney brush borders on PYY(3-36). In mice, pretreatment with actinonin
      significantly prolonged the anorectic effect of PYY(3-36) and maintained higher
      PYY(3-36) plasma levels than treatment with PYY(3-36) alone. These studies
      suggest that inhibiting the degradation of PYY(3-36) using specific inhibitor
      therapies and/or the design of analogues resistant to cleavage by meprins may be
      useful to antiobesity therapeutics.

PMID- 21952245
TI  - Mesenchymal activin-A overcomes defective human trisomy 21 trophoblast fusion.
AB  - Placental development is markedly abnormal in trisomy 21 (T21) pregnancies. We
      hypothesized that abnormal paracrine cross talk between the fetal mesenchymal
      core and the trophoblast might be involved in the defect of syncytiotrophoblast
      formation and function. In a large series of primary cultured human
      cytotrophoblasts isolated from second-trimester control (n = 44) and T21
      placentae (n = 71), abnormal trophoblast fusion and differentiation was observed
      in more than 90% of T21 cases. We then isolated and cultured villous mesenchymal
      cells from control (n = 10) and T21 placentae (n = 8) and confirmed their fetal
      origin. Conditioned medium of control mesenchymal cells overcame the abnormal
      trophoblast fusion of T21 cytotrophoblasts by activating the TGFbeta signaling
      pathway, as shown by the phosphospecific protein microarray analysis and the use
      of TGFbeta signaling pathway antagonists. Using protein arrays, we further
      analyzed the cytokines present in the conditioned medium from control and T21
      mesenchymal cells. Activin-A was identified as strongly secreted by cells from
      both sources, but at a significantly (P < 0.01) lower level in the case of T21
      mesenchymal cells. Recombinant activin-A stimulated T21 trophoblast fusion.
      Blocking activin-A antibody inhibited the fusion induced by conditioned medium
      and exogenous activin-A. Furthermore, follistatin, an activin-A binding protein
      largely secreted by T21 mesenchymal cells, inhibited the conditioned medium
      fusogenic activity. These results show that the defective trophoblast fusion and
      differentiation associated with T21 can be overcome in vitro and reveal the key
      role of the fetal mesenchymal core in human trophoblast differentiation.

PMID- 21952246
TI  - Identification and functional characterization of zebrafish solute carrier
      Slc16a2 (Mct8) as a thyroid hormone membrane transporter.
AB  - Most components of the thyroid system in bony fish have been described and
      characterized, with the notable exception of thyroid hormone membrane
      transporters. We have cloned, sequenced, and expressed the zebrafish solute
      carrier Slc16a2 (also named monocarboxylate transporter Mct8) cDNA and
      established its role as a thyroid hormone transport protein. The cloned cDNA
      shares 56-57% homology with its mammalian orthologs. The 526-amino-acid sequence
      contains 12 predicted transmembrane domains. An intracellular N-terminal PEST
      domain, thought to be involved in proteolytic processing of the protein, is
      present in the zebrafish sequence. Measured at initial rate and at the
      body/rearing temperature of zebrafish (26 C), T(3) uptake by zebrafish Slc16a2 is
      a saturable process with a calculated Michaelis-Menten constant of 0.8 MUM T(3).
      The rate of T(3) uptake is temperature dependent and Na(+) independent.
      Interestingly, at 26 C, zebrafish Slc16a2 does not transport T(4). This implies
      that at a normal body temperature in zebrafish, Slc16a2 protein is predominantly
      involved in T(3) uptake. When measured at 37 C, zebrafish Slc16a2 transports T(4)
      in a Na(+)-independent manner. In adult zebrafish, the Slc16a2 gene is highly
      expressed in brain, gills, pancreas, liver, pituitary, heart, kidney, and gut.
      Beginning from the midblastula stage, Slc16a2 is also expressed during zebrafish
      early development, the highest expression levels occurring 48 h after
      fertilization. This is the first direct evidence for thyroid hormone membrane
      transporters in fish. We suggest that Slc16a2 plays a key role in the local
      availability of T(3) in adult tissues as well as during the completion of
      morphogenesis of primary organ systems.

PMID- 21952248
TI  - TLR4 activation and IL-6-mediated cross talk between adipocytes and mononuclear
      cells synergistically stimulate MMP-1 expression.
AB  - Obesity is associated with increased monocyte infiltration into adipose tissue
      and hence increased interaction between adipocytes and monocytes. Although it has
      been shown that matrix metalloproteinases (MMP) play a critical role in adipose
      tissue development, the effect of adipocyte and monocyte interaction on MMP
      production remains largely unknown. Furthermore, although it has been shown that
      Toll-like receptor 4 (TLR4), a receptor mediating innate immune response, plays
      an important role in the obesity-associated inflammation and insulin resistance,
      the effect of TLR4 activation in coculture of adipocytes and monocytes on MMP
      production has not been investigated. In this study, we cocultured adipocytes
      with U937 mononuclear cells in a Transwell coculture system and activated TLR4
      with lipopolysaccharide or palmitic acid. We found that TLR4 activation and the
      coculture had a synergistic effect on MMP-1 production. In our further
      investigation on the underlying mechanisms, it was indicated that adipocyte
      derived IL-6 and TLR4 activation acted in concert to synergistically stimulate
      MMP-1 expression by U937 cells. Taken together, this study has uncovered a novel
      mechanism potentially involved in MMP-1 up-regulation in adipose tissue, which
      may facilitate adipose tissue development and obesity.

PMID- 21952247
TI  - Loss of Foxd3 results in decreased beta-cell proliferation and glucose
      intolerance during pregnancy.
AB  - A complete molecular understanding of beta-cell mass expansion will be useful for
      the improvement of therapies to treat diabetic patients. During normal periods of
      metabolic challenges, such as pregnancy, beta-cells proliferate, or self-renew,
      to meet the new physiological demands. The transcription factor Forkhead box D3
      (Foxd3) is required for maintenance and self-renewal of several diverse
      progenitor cell lineages, and Foxd3 is expressed in the pancreatic primordium
      beginning at 10.5 d postcoitum, becoming localized predominantly to beta-cells
      after birth. Here, we show that mice carrying a pancreas-specific deletion of
      Foxd3 have impaired glucose tolerance, decreased beta-cell mass, decreased beta
      cell proliferation, and decreased beta-cell size during pregnancy. In addition,
      several genes known to regulate proliferation, Foxm1, Skp2, Ezh2, Akt2, and
      Cdkn1a, are misregulated in islets isolated from these Foxd3 mutant mice.
      Together, these data place Foxd3 upstream of several pathways critical for beta
      cell mass expansion in vivo.

PMID- 21952249
TI  - Influence of estrogens on GH-cell network dynamics in females: a live in situ
      imaging approach.
AB  - The secretion of endocrine hormones from pituitary cells finely regulates a
      multitude of homeostatic processes. To dynamically adapt to changing
      physiological status and environmental stimuli, the pituitary gland must undergo
      marked structural and functional plasticity. Endocrine cell plasticity is thought
      to primarily rely on variations in cell proliferation and size. However, cell
      motility, a process commonly observed in a variety of tissues during development,
      may represent an additional mechanism to promote plasticity within the adult
      pituitary gland. To investigate this, we used multiphoton time-lapse imaging
      methods, GH-enhanced green fluorescent protein transgenic mice and sexual
      dimorphism of the GH axis as a model of divergent tissue demand. Using these
      methods to acutely (12 h) track cell dynamics, we report that ovariectomy induces
      a dramatic and dynamic increase in cell motility, which is associated with gross
      GH-cell network remodeling. These changes can be prevented by estradiol
      supplementation and are associated with enhanced network connectivity as
      evidenced by increased coordinated GH-cell activity during multicellular calcium
      recordings. Furthermore, cell motility appears to be sex-specific, because
      reciprocal alterations are not detected in males after castration. Therefore, GH
      cell motility appears to play an important role in the structural and functional
      pituitary plasticity, which is evoked in response to changing estradiol
      concentrations in the female.

PMID- 21952250
TI  - Co-administration of ondansetron decreases the analgesic efficacy of tramadol in
      humans.
AB  - Tramadol, a central analgesic acting on serotonin neurotransmission, is often co
      used with ondansetron, a 5-HT(3) antagonist, for the management of postoperative
      pain to decrease nausea and vomiting. The aim of the study is to test the
      hypothesis that this drug combination raises tramadol requirement by patient
      controlled analgesia (PCA). Forty patients undergoing hernioplasty or
      thyroidectomy were enrolled in a randomized, controlled study and allocated to
      receive ondansetron 4 mg i.v. (n = 20) or saline (n = 20). At 0, 1, 2, 4 and 24 h
      of PCA, tramadol consumption was evaluated. Tramadol consumption (mg * kg(-1) *
      h(-1)) was higher in the ondansetron group at the 2-hour time point compared to
      the control group (0.24 +/- 0.1 vs. 0.17 +/- 0.16; p = 0.01). Our study suggests
      that ondansetron acutely reduces the analgesic efficacy of tramadol.

PMID- 21952251
TI  - Evolution of the inflammatory and fibroproliferative responses during resolution
      and repair after ventilator-induced lung injury in the rat.
AB  - BACKGROUND: The time course and mechanisms of resolution and repair, and the
      potential for fibrosis following ventilation-induced lung injury (VILI), are
      unclear. We sought to examine the pattern of inflammation, injury, repair, and
      fibrosis following VILI. METHODS: Sixty anesthetized rats were subject to high
      stretch; low-stretch, or sham ventilation, and randomly allocated to undergo
      periods of recovery of 6, 24, 48, and 96 h, and 7 and 14 days. Animals were then
      reanesthetized, and the extent of lung injury, inflammation, and repair
      determined. RESULTS: No injury was seen following low-stretch or sham
      ventilation. VILI caused severe lung injury, maximal at 24 h, but largely
      resolved by 96 h. Arterial oxygen tension decreased from a mean (SD) of 144.8
      (4.1) mmHg to 96.2 (10.3) mmHg 6 h after VILI, before gradually recovering to
      131.2 (14.3) mmHg at 96 h. VILI induced an early neutrophilic alveolitis and a
      later lymphocytic alveolitis, followed by a monocyte/macrophage infiltration.
      Alveolar tumor necrosis factor-alpha, interleukin-1beta, and transforming growth
      factor-beta1 concentrations peaked at 6 h and returned to baseline within 24 h,
      while interleukin-10 remained increased for 48 h. VILI generated a marked but
      transient fibroproliferative response, which restored normal lung architecture.
      There was no evidence of fibrosis at 7 and 14 days. CONCLUSIONS: High-stretch
      ventilation caused severe lung injury, activating a transient inflammatory and
      fibroproliferative repair response, which restored normal lung architecture
      without evidence of fibrosis.

PMID- 21952253
TI  - Prolonged central venous desaturation measured by continuous oximetry is
      associated with adverse outcomes in pediatric cardiac surgery.
AB  - BACKGROUND: The role of continuous central venous oxygen saturation (ScvO2)
      oximetry during pediatric cardiac surgery for predicting adverse outcomes is not
      known. Using a recently available continuous ScvO2 oximetry catheter, we examined
      the association between venous oxygen desaturations and patient outcomes. We
      hypothesized that central venous oxygen desaturations are associated with adverse
      clinical outcomes. METHODS: Fifty-four pediatric patients undergoing cardiac
      surgery were prospectively enrolled in an unblinded observational study. ScvO2
      was measured continuously in the operating room and for up to 24 h post-Intensive
      Care Unit admission. The relationships between ScvO2 desaturations, clinical
      outcomes, and major adverse events were determined. RESULTS: More than 18 min of
      venous saturations less than 40% were associated with major adverse events with
      100% sensitivity and 97.6% specificity. Significant correlations resulted between
      the ScvO2 area under the curve less than 40% and creatinine clearance at 12 h in
      the Intensive Care Unit (r = -0.58), Intensive Care Unit length of stay (r =
      0.56), max inotrope use (r = 0.52), inotrope use at 24 h (r = 0.40), inotrope
      index score (r = 0.39), hospital length of stay (r = 0.36), and length of
      intubation (r = 0.32). CONCLUSIONS: We demonstrate that ScvO2 desaturations by
      continuous oximetry are associated with major adverse events in pediatric
      patients undergoing cardiac surgery. The most significant associations with major
      adverse events are seen in patients with greater than 18 min of central venous
      saturations less than 40%. Our results support the further investigation of ScvO2
      as a potential target parameter in high-risk pediatric patients to minimize the
      risk of major adverse events.

PMID- 21952252
TI  - Advances in the management of sepsis and the understanding of key immunologic
      defects.
AB  - Anesthesiologists are increasingly confronting the difficult problem of caring
      for patients with sepsis in the operating room and in the intensive care unit.
      Sepsis occurs in more than 750,000 patients in the United States annually and is
      responsible for more than 210,000 deaths. Approximately 40% of all intensive care
      unit patients have sepsis on admission to the intensive care unit or experience
      sepsis during their stay in the intensive care unit. There have been significant
      advances in the understanding of the pathophysiology of the disorder and its
      treatment. Although deaths attributable to sepsis remain stubbornly high, new
      treatment algorithms have led to a reduction in overall mortality. Thus, it is
      important for anesthesiologists and critical care practitioners to be aware of
      these new therapeutic regimens. The goal of this review is to include practical
      points on important advances in the treatment of sepsis and provide a vision of
      future immunotherapeutic approaches.

PMID- 21952254
TI  - Invasive and concomitant noninvasive intraoperative blood pressure monitoring:
      observed differences in measurements and associated therapeutic interventions.
AB  - BACKGROUND: Noninvasive (NIBP) and intraarterial (ABP) blood pressure monitoring
      are used under different circumstances and may yield different values. The
      authors endeavored to characterize these differences and hypothesized that there
      could be differences in interventions associated with the use of ABP alone
      ([ABP]) versus ABP in combination with NIBP ([ABP+NIBP]). METHODS: Simultaneous
      measurements of ABP and NIBP made during noncardiac cases were extracted from
      electronic anesthesia records; the differences were subjected to regression
      analysis. Records of blood products, vasopressors, and antihypertensives
      administered were also extracted, and associations between the use of these
      therapies and monitoring strategy ([ABP] vs. [ABP+NIBP]) were tested using
      univariate, multivariate, and propensity score matched analyses. RESULTS: Among
      24,225 cases, 63% and 37% used [ABP+NIBP] and [ABP], respectively. Systolic NIBP
      was likely to be higher than ABP when ABP was less than 111 mmHg and lower than
      ABP otherwise. Among patients with hypotension, transfusion occurred in 27%
      versus 43% of patients in the [ABP+NIBP] versus [ABP] group, respectively (odds
      ratio = 0.4; 95% CI 0.35-0.46), and 7% versus 18% of patients in the [ABP+NIBP]
      versus [ABP] group received vasopressor infusions, respectively (P < 0.01). Among
      hypertensive patients, 12% versus 44% of those in the [ABP+NIBP] versus [ABP]
      group received antihypertensive agents, respectively (P < 0.01). CONCLUSIONS:
      NIBP was generally higher than ABP during periods of hypotension and lower than
      ABP during periods of hypertension. The use of NIBP measurements to supplement
      ABP measurements was associated with decreased use of blood transfusions,
      vasopressor infusions, and antihypertensive medications compared with the use of
      ABP alone.

PMID- 21952255
TI  - Eye drops and tears.

PMID- 21952256
TI  - Interactions between nitrous oxide and tissue plasminogen activator in a rat
      model of thromboembolic stroke.
AB  - BACKGROUND: Preclinical evidence in rodents has suggested that inert gases, such
      as xenon or nitrous oxide, may be promising neuroprotective agents for treating
      acute ischemic stroke. This has led to many thinking that clinical trials could
      be initiated in the near future. However, a recent study has shown that xenon
      interacts with tissue-type plasminogen activator (tPA), a well-recognized
      approved therapy of acute ischemic stroke. Although intraischemic xenon inhibits
      tPA-induced thrombolysis and subsequent reduction of brain damage, postischemic
      xenon virtually suppresses both ischemic brain damage and tPA-induced brain
      hemorrhages and disruption of the blood-brain barrier. The authors investigated
      whether nitrous oxide could also interact with tPA. METHODS: The authors
      performed molecular modeling of nitrous oxide binding on tPA, characterized the
      concentration-dependent effects of nitrous oxide on tPA enzymatic and
      thrombolytic activity in vitro, and investigated the effects of intraischemic and
      postischemic nitrous oxide in a rat model of thromboembolic acute ischemic
      stroke. RESULTS: The authors demonstrate nitrous oxide is a tPA inhibitor,
      intraischemic nitrous oxide dose-dependently inhibits tPA-induced thrombolysis
      and subsequent reduction of ischemic brain damage, and postischemic nitrous oxide
      reduces ischemic brain damage, but in contrast with xenon, it increases brain
      hemorrhages and disruption of the blood-brain barrier. CONCLUSIONS: In contrast
      with previous studies using mechanical acute stroke models, these data obtained
      in a clinically relevant rat model of thromboembolic stroke indicate that nitrous
      oxide should not be considered a good candidate agent for treating acute ischemic
      stroke compared with xenon.

PMID- 21952257
TI  - Observation of long-range f-f interactions between two f-electronic systems in
      quadruple-decker phthalocyanines.
AB  - Homo and heteronuclear quadruple-decker phthalocyanine tetramers containing Y(3+)
      and/or magnetically anisotropic lanthanide ions such as Tb(3+), Dy(3+), and
      Er(3+) have been synthesized, and their magnetic properties have been elucidated,
      giving clear evidence of the long-range interactions between two f-electronic
      centers.

PMID- 21952258
TI  - Development of the GABAergic system from birth to adolescence.
AB  - The neurotransmitter GABA (gamma-aminobutyric acid), acting via inotropic GABA(A)
      and metabotropic GABA(B) receptors, plays an essential role in a variety of
      distinct neuronal processes, including regulation of neuronal excitability,
      determination of temporal aspects of spike trains, control of the size and
      propagation of neuronal assemblies, generation of oscillatory activity, and
      neuronal plasticity. Although the developmental switch between excitatory and
      inhibitory GABA(A) receptor-mediated responses is widely appreciated, the fact
      that the postnatal maturation of the GABAergic system lasts until late
      adolescence is not so persuasively promoted. This review summarizes recent
      knowledge of the maturation of various aspects of the GABAergic systems, like
      functional expression of GABA synthesizing/degrading enzymes and transporters,
      density of GABAergic synapses, GABAergic projection patterns, GABA receptor
      subunit composition, and properties of GABAergic interneurons, with an emphasis
      on the late developmental alterations. In addition, some aspects of the
      development of mental capabilities during adolescence and their relation the
      delayed maturation of the GABAergic system are presented.

PMID- 21952259
TI  - High-throughput rheology in a microfluidic device.
AB  - High-throughput rheological measurements in a microfluidic device are
      demonstrated. A series of microrheology samples are generated as droplets in an
      immiscible spacer fluid using a microfluidic T-junction. The compositions of the
      sample droplets are continuously varied over a wide range. Rheology measurements
      are made in each droplet using multiple particle tracking microrheology. We
      review critical design and operating parameters, including the droplet size, flow
      rates and rapid fabrication methods. Validation experiments are performed by
      measuring the solution viscosity of glycerine and the biopolymer heparin as a
      function of concentration. Overall, the combination of microrheology with
      microfluidics maximizes the number of rheological measurements while
      simultaneously minimizing the sample preparation time and amount of material, and
      should be particularly suited to the characterization of scarce or expensive
      materials.

PMID- 21952261
TI  - Surprise! A unifying model of dorsal anterior cingulate function?

PMID- 21952260
TI  - Heterogeneity of CNS myeloid cells and their roles in neurodegeneration.
AB  - The diseased brain hosts a heterogeneous population of myeloid cells, including
      parenchymal microglia, perivascular cells, meningeal macrophages and blood-borne
      monocytes. To date, the different types of brain myeloid cells have been
      discriminated solely on the basis of their localization, morphology and surface
      epitope expression. However, recent data suggest that resident microglia may be
      functionally distinct from bone marrow- or blood-derived phagocytes, which invade
      the CNS under pathological conditions. During the last few years, research on
      brain myeloid cells has been markedly changed by the advent of new tools in
      imaging, genetics and immunology. These methodologies have yielded unexpected
      results, which challenge the traditional view of brain macrophages. On the basis
      of these new studies, we differentiate brain myeloid subtypes with regard to
      their origin, function and fate in the brain and illustrate the divergent
      features of these cells during neurodegeneration.

PMID- 21952262
TI  - Regulation of complex I by Engrailed is complex too.

PMID- 21952263
TI  - Receptors in (e)motion.

PMID- 21952264
TI  - Is that a bathtub in your kitchen?

PMID- 21952265
TI  - Maintaining a Highwire act.

PMID- 21952266
TI  - Direct implantation of VX-2 carcinoma: a new rabbit bone model using a three
      dimensional matrix as a carrier for the tumor cells.
AB  - BACKGROUND: Animal bone models are inevitable for musculoskeletal research. The
      induction of a local bone tumor is complex and time consuming. In this study a
      new model is presented using a direct implantation of tumor cells into the bone
      without a preliminary passaging of the cells. METHODS: A three-dimensional matrix
      consisting of alginate spheroids and carrying the VX-2 tumor suspension was used
      for implantation into the bone of 6 female New Zealand white rabbits. X-ray
      imaging, CT and MRI scans as well as a histological examination were carried out.
      RESULTS: All rabbits developed local bone tumor in the metaphysis of the femoral
      leg. Bone tumor was identifiable on average 6.2 weeks after implantation.
      Fluoroscopy, CT and MRI scans showed a cortical reaction but no destruction of
      the compact bone together with a mean tumor size of 14 mm. Histological
      examination revealed a tumor infiltration with an activation of osteoclasts and
      an osteoclastic resorption. CONCLUSION: The direct implantation of a VX-2 tumor
      suspension into the rabbit bone using alginate spheroids is an effective and
      reproducible way to successfully induce bone tumor. This new animal model allows
      further examination of surgical and minimal invasive therapy in musculoskeletal
      research.

PMID- 21952268
TI  - C-N bond formation via ligand-induced nucleophilicity at a coordinated
      triamidoamine ligand.
AB  - Reaction of (N(3)N)ZrX complexes (X = amido, Cl(-), CH(3)(-)) with carbodiimide
      substrates results in insertion into an Zr-N bond of the triamidoamine ligand
      rather than the Zr-X bond as has been observed for related (N(3)N)ZrX complexes
      (X = PR(2)(-), AsR(2)(-)).

PMID- 21952269
TI  - Electrogenerated chemiluminescence triggered by electroseparation of Ru(bpy)3(2+)
      across a supported liquid membrane.
AB  - We demonstrate here for the first time the detection of electrogenerated
      chemiluminescence (ECL) upon selective, electrochemically triggered tris(2,2'
      bipyridyl)ruthenium(II) (Ru(bpy)(3)(2+)) transport across a supported liquid
      membrane doped with a lipophilic cation-exchanger. This approach allows one to
      separate the location of ECL generation from the sample compartment, thereby
      avoiding the contamination of the sample with compounds necessary for ECL.

PMID- 21952267
TI  - Is baseline physical activity a determinant of participation in worksite walking
      clubs? Data from the HealthWorks Trial.
AB  - BACKGROUND: Some evidence suggests that physical activity programs mainly attract
      employees who are already active. This study examined the degree to which
      baseline physical activity was associated with enrollment in worksite walking
      clubs. METHODS: All variables were measured at baseline. Walking club
      participation was measured over 2 years. There were 642 individuals from 3
      worksites with complete data available for logistic regression analyses. RESULTS:
      Baseline physical activity [OR (95% CI)=1.00 (0.99, 1.01)] was not a significant
      predictor of walking club participation. Participants who were older [OR=1.03
      (1.01, 1.04)] or indicated more social support for physical activity [OR=1.13
      (1.02, 1.25)] had significantly higher odds of participation relative to those
      who were younger or indicated less social support, respectively. In addition, men
      [OR=-0.25 (0.18, 0.36)] and employees from the second worksite [OR=-0.41 (0.25,
      0.67)] had significantly lower odds of participation relative to women and
      employees from the first or third worksites, respectively. Sensitivity analyses
      arrived at similar conclusions. CONCLUSIONS: Worksite walking clubs were
      appealing across varying levels of physical activity. Future research should
      improve marketing and program design to engage harder-to-reach segments of the
      workforce, particularly young men and those with limited social support.

PMID- 21952270
TI  - Second harmonic generation monitoring of nitric acid extraction by a monoamide at
      the water-dodecane interface.
AB  - The interface dynamic properties of a monoamide extractant with potential for
      application to the front end of the nuclear cycle and to waste treatment are
      examined by second harmonic generation. The results are compared with bulk nitric
      ion titration and surface pressure measurements. SH static studies show the
      extractant reaching the interface and accurately match the IFT measurements. The
      main feature of the SH dynamic studies is a chaotic fluctuation period, strongly
      related to intense extraction. Fluctuations are a signature of the interface
      behaviour during the extraction process. Vertical development of the interface,
      often called protrusion, remains the most probable origin of the measured
      fluctuation. Additionally, interfacial measurements show a non-monotonic lag time
      during extraction, probably related to cooperative effects not observed in the
      bulk at the working concentration. Such mutual behaviour could be a supplementary
      prerequisite for the ion transfer across this liquid-liquid interface.

PMID- 21952271
TI  - Self-assembled layered hybrid [Ru(bpy)3]2+/manganese(III,IV) oxide: a new and
      efficient strategy for water oxidation.
AB  - For the first time, a self-assembled layered hybrid
      [Ru(bpy)(3)](2+)/manganese(III,IV) as a water oxidizing system is reported.

PMID- 21952273
TI  - Combined modality treatment with chemotherapy, radiation therapy, bevacizumab,
      and erlotinib in patients with locally advanced squamous carcinoma of the head
      and neck: a phase II trial of the Sarah Cannon oncology research consortium.
AB  - PURPOSE: : The aim of the study was to evaluate the feasibility and efficacy of
      adding bevacizumab and erlotinib to concurrent chemoradiation therapy for first
      line treatment of patients with locally advanced squamous carcinoma of the head
      and neck. METHODS: : Sixty previously untreated patients with squamous carcinoma
      of the head and neck (36 with oropharyngeal primaries; 83% men; median age, 56
      years; 73% stage IV) received induction chemotherapy with 6 weeks of paclitaxel,
      carboplatin, infusional 5-fluorouracil, and bevacizumab; this treatment was
      followed by radiation therapy, weekly paclitaxel, bevacizumab, and erlotinib.
      RESULTS: : After a median follow up of 32 months, the estimated 3-year
      progression-free and overall survival rates are 71% and 82%, respectively. Sixty
      five percent of patients had major responses after induction therapy; after
      completion of therapy, 95% of patients had either partial or complete response
      radiographically. As expected, grade 3/4 mucosal toxicity occurred frequently
      (88%) during combined modality; no unexpected toxicity resulted from the addition
      of bevacizumab and erlotinib. CONCLUSIONS: : The addition of bevacizumab and
      erlotinib to first-line combined modality therapy was feasible in a community
      based setting, producing toxicity comparable to other effective combined modality
      regimens for head and neck cancer. The high level of efficacy suggests that
      incorporation of these targeted agents into first-line therapy should be further
      explored.

PMID- 21952274
TI  - Commentary: bevacizumab and erlotinib with chemoradiation for head and neck
      cancer.

PMID- 21952275
TI  - Therapeutic cancer vaccine development: will it ride the wave of new
      immunomodulatory agents?.

PMID- 21952276
TI  - Melanoma vaccines.
AB  - There is much renewed activity in the testing of vaccines that target metastatic
      melanoma, driven by successes in other areas, most notably prostate cancer. Yet,
      sound evidence that any stand-alone vaccination approach has clinical benefit
      against melanoma remains lacking. With phase III studies showing no efficacy of
      promising whole-cell vaccines and heat shock proteins, peptide and dendritic cell
      vaccines remain the most common approaches. A major obstacle to progress is the
      lack of any surrogate measures in phase II studies that associate meaningfully
      with clinical benefit, and this is further complicated by phase III evidence in
      prostate cancer that immunologic monitoring, tumor response rates, or even times
      to tumor progression may not accurately predict survival benefit. The area with
      the most progress has been in combining vaccines with other systemic
      immunostimulatory agents. Although no vaccine has been found which fulfills the
      prediction from murine models that they can enhance the efficacy of ipilimumab,
      combining a peptide vaccination with high-dose interleukin 2 was shown to enhance
      complete and overall response rates compared with interleukin 2 alone. These
      promising combinations continue to struggle with the same unresolved issues that
      have plagued melanoma vaccines from the beginning-what are the best antigens to
      target, what are the best methods of vaccination, and what constitutes a
      sufficient immune response to be of value? Virtually no progress has been made
      toward answering these questions.

PMID- 21952277
TI  - Vaccines for colorectal cancer and renal cell carcinoma.
AB  - Vaccines have shown promise for the prevention and treatment of solid tumors.
      Colorectal cancer and renal cell carcinoma are common malignancies that may be
      amenable to vaccine strategies. This review summarizes target antigens in
      colorectal and renal cell carcinoma, discusses some of the vaccine approaches in
      development, and details the results of pivotal phase III trials evaluating
      therapeutic vaccines in patients with advanced colorectal and renal cell
      carcinoma. Finally, some of the challenges with vaccine development for
      colorectal and renal cell carcinoma are described.

PMID- 21952278
TI  - Update on prostate cancer vaccines.
AB  - The recent approval of Sipuleucel-T (Dendreon, Seattle, WA) from the Food and
      Drug Administration for the treatment of men with asymptomatic or minimally
      symptomatic castrate-resistant prostate cancer was a landmark in cancer
      immunotherapy, making this the first cancer "vaccine" approved for use in a
      treatment setting. This approval has led to renewed interest in cancer vaccines
      and to the recognition that prostate cancer represents an immunologically
      sensitive disease. At the current time, several vaccine approaches are under
      clinical investigation. These include viral vectors, antigen-loaded dendritic
      cells, and DNA vaccines. Each approach has its own set of advantages and
      disadvantages. This review will introduce the basic technology underlying these
      different vaccines and briefly discuss completed and ongoing clinical trials. As
      a great number of prostate cancer vaccines have been investigated in both
      preclinical and clinical settings, we will focus primarily on vaccines that are
      currently in clinical trials, as ascertained by a recent inquiry of the clinical
      trials database, www.clinicaltrials.gov.

PMID- 21952279
TI  - Synthetic vaccine for the treatment of lesions caused by high risk human
      papilloma virus.
AB  - Until recently, therapeutic cancer vaccines only sporadically led to long-term
      clinical responses. We here report on a novel vaccine modality, characterized by
      the administration of long (23-45 amino acids) synthetic peptides in incomplete
      Freund adjuvant (mineral oil-based, Montanide ISA-51), delivered subcutaneously.
      Such vaccines were first demonstrated to be much more potent in preclinical T
      cell response induction and tumor therapy experiments than short major
      histocompatibility complex class I-binding peptides that have been used
      extensively in the clinic. A long-peptide vaccine consisting of 13 overlapping
      peptides, together covering the entire length of the 2 oncogenic proteins E6 and
      E7 of high-risk human papilloma virus type 16 (HPV16), caused complete regression
      of all lesions and eradication of virus in 9 of 20 women with high-grade vulvar
      intraepithelial neoplasia. The nature and strength of the vaccine-induced T-cell
      response were significantly correlated with the clinical response. This vaccine
      promises to be of use, not only in patients with premalignant lesions caused by
      high-risk HPV16, but also in patients with malignant tumors caused by this virus,
      including HPV16-positive cervical cancer, anal cancer, and head and neck cancer.

PMID- 21952280
TI  - Lung cancer vaccines.
AB  - To date, in lung cancer, early attempts to modulate the immune system via vaccine
      based therapeutics have been unsuccessful. An improved understanding of tumor
      immunology has facilitated the production of more sophisticated lung cancer
      vaccines. It is anticipated that it will likely require multiple epitopes of a
      diverse set of genes restricted to multiple haplotypes to generate a truly
      effective vaccine that is able to overcome the various immunologic escape
      mechanisms that tumors employ. Other issues to overcome include optimal patient
      selection, which adjuvant agent to use, and how to adequately monitor for an
      immunologic response. This review discusses the most promising vaccination
      strategies for non-small cell lung cancer including the allogeneic tumor cell
      vaccine belagenpumatucel-L, which is a mixture of 4 allogeneic non-small cell
      lung cancer cell lines genetically modified to secrete an antisense
      oligonucleotide to transforming growth factor beta2 and 3 other target protein
      specific vaccines designed to induce responses against melanoma-associated
      antigen A3, mucin 1, and epidermal growth factor.

PMID- 21952282
TI  - Tumor-specific antigens and immunologic adjuvants in cancer immunotherapy.
AB  - T cell-based cancer immunotherapy relies on advancements made over the last 20
      years on the molecular mechanisms underlying the antigenicity of tumors. This
      review focuses on human tumor antigens recognized by T lymphocytes, particularly
      the reasons why some are tumor-specific but others are not, and on the
      immunologic adjuvants used in clinical trials on therapeutic vaccination with
      defined tumor antigens.

PMID- 21952283
TI  - Autologous versus allogeneic cell-based vaccines?
AB  - Devitalized tumor cells either autologous or allogeneic have been used as anti
      cancer vaccines with the purpose of facilitating the induction of an immune
      response able to destroy growing tumor cells since the identification of tumor
      antigens was deemed not to be necessary, particularly in the autologous system.
      Such vaccines were tested first in animal models and then in the clinics as
      unmodified tumor cells or after insertion of genes coding for factors known to
      increase the immune response against tumors. These vaccines were usually given by
      subcutaneous injections along with different immunological adjuvants. Such
      immunization approaches were found to be effective in mice when carried out in a
      tumor preventive setting but significantly less in the therapeutic context, that
      is, in the presence of an established tumor. By analyzing several clinical trials
      of vaccination using either autologous or allogeneic unmodified and gene-modified
      tumor cells published in the last 10 to 15 years, we conclude for a lack of
      sufficient evidence for efficacy of this strategy in inducing both a strong
      immune response and a therapeutic response. A potential variant of this strategy
      is the direct intratumoral injection of immunostimulatory genes delivered by
      vectors in vivo. But even this approach failed to provide a statistically
      significant clinical benefit for the cancer patients.We also point out the
      inherent drawbacks of the tumor cell-based vaccine strategy that include (a) a
      limited frequency by which human tumor lines can be obtained from clinical
      samples, (b) the low number of available cells for vaccination, (c) the release
      of immune-suppressive factors by tumor cells, and (d) the cost and time necessary
      for standardization and collecting/expanding a number of cells according to the
      approved regulatory requirements. Thus, taking into consideration the new
      developments in cancer vaccines, we believe that tumor cell-based vaccines should
      be dismissed as anti-cancer vaccines unless a clear benefit could be demonstrated
      by the few ongoing trials of combination with new immunomodulating reagents (eg,
      anti-CTLA4, PD-1, chemotherapy).

PMID- 21952284
TI  - Dendritic cells: indispensable?
AB  - Dendritic cells (DCs) control the initiation and differentiation of T cells. In
      the steady state, DCs mediate tolerance. To achieve immunization, the tolerogenic
      function of DCs must be switched off by inducing their maturation with
      appropriate "adjuvants." Dendritic cells form a system composed of distinct
      subsets that differ in their expression of endocytic and signaling receptors.
      These subsets have different capacities to differentiate and polarize T cells and
      to cross-present antigen to expand CD8+ T cells. Optimization of vaccines is
      possible by exploiting the unique biological properties of DCs.

PMID- 21952281
TI  - Evaluation of current cancer immunotherapy: hemato-oncology.
AB  - Hematologic malignancies were the first diseases in clinical oncology for which
      the potential of harnessing the immune system as targeted therapy was
      unequivocally demonstrated. Unfortunately, the use of this highly efficacious
      modality has been limited to only a subset of patients and diseases because of
      immune-mediated toxicities resulting from incomplete specificity, and disease
      specific determinants of sensitivity versus resistance to immune effector
      mechanisms. Recent studies, however, have begun to elucidate the molecular basis
      of the observed clinical effects allowing the rational development of next
      generation of immunotherapeutic combinations. We discuss here cancer antigen
      targets in hematologic malignancies and the specific approaches to induce
      immunity being pursued, the importance of modulating the host immunoregulatory
      environment, and the special features of immunological monitoring in clinical
      investigation. The hematologic malignancies represent an ideal setting for the
      development of immunotherapy due to logistical, clinical monitoring, and disease
      biology factors and may represent an exemplar for immune-based treatment in other
      cancer types.

PMID- 21952286
TI  - Prerequisites for the antitumor vaccine-like effect of chemotherapy and
      radiotherapy.
AB  - For a long time, anticancer therapies were believed to work (and hence convey a
      therapeutic benefit) either by killing cancer cells or by inducing a permanent
      arrest in their cell cycle (senescence). In both scenarios, the efficacy of
      anticancer regimens was thought to depend on cancer cell-intrinsic features only.
      More recently, the importance of the tumor microenvironment (including stromal
      and immune cells) has been recognized, along with the development of therapies
      that function by modulating tumor cell-extrinsic pathways. In particular, it has
      been shown that some chemotherapeutic and radiotherapeutic regimens trigger
      cancer cell death while stimulating an active immune response against the tumor.
      Such an immunogenic cell death relies on the coordinated emission of specific
      signals from dying cancer cells and their perception by the host immune system.
      The resulting tumor-specific immune response is critical for the eradication of
      tumor cells that may survive therapy. In this review, we discuss the molecular
      mechanisms that underlie the vaccine-like effects of some chemotherapeutic and
      radiotherapeutic regimens, with particular attention to the signaling pathways
      and genetic elements that constitute the prerequisites for immunogenic anticancer
      therapy.

PMID- 21952285
TI  - The present and future of peptide vaccines for cancer: single or multiple, long
      or short, alone or in combination?
AB  - Peptide vaccines incorporate one or more short or long amino acid sequences as
      tumor antigens, combined with a vaccine adjuvant. Thus, they fall broadly into
      the category of defined antigen vaccines, along with vaccines using protein,
      protein subunits, DNA, or RNA. They remain one of the most immunogenic
      approaches, based on measures of T-cell response in the blood or in draining
      lymph nodes. However, existing peptide vaccines have had limited success at
      inducing clinical tumor regressions, despite reliable induction of T-cell
      responses. Several new developments offer promise for improving peptide vaccines,
      including use of long peptides, optimization of adjuvants including toll-like
      receptor agonists, and combination with systemic therapies that may reduce tumor
      associated immune dysfunction, such as blockade of PD-1/PD-L1 interactions. To
      apply these new approaches optimally, it will be critical to study their effects
      in the context of defined antigens, for which peptide vaccines are optimal.

PMID- 21952287
TI  - Viral vector-based therapeutic cancer vaccines.
AB  - Most viruses are naturally immunogenic and can be engineered to express tumor
      antigen transgenes. Moreover, many types of recombinant viruses have been shown
      to infect professional antigen-presenting cells, specifically dendritic cells,
      and express their transgenes. This enhanced presentation of tumor antigens to the
      immune system has led to an increase in the frequency and avidity of cytotoxic T
      lymphocytes that target tumor cells expressing the tumor antigen(s) encoded in
      the vaccine vector. Logistically, recombinant viruses can be produced,
      administered, and quality controlled more easily compared with other
      immunotherapy strategies. The intrinsic properties of each virus have distinct
      advantages and disadvantages, which can determine their applicability in a
      particular therapeutic setting. The disadvantage of some vectors is the
      development of host-induced neutralizing antibodies to the vector itself, thus
      limiting its continued use. The "off-the-shelf" nature of viral vaccine platforms
      renders them exceptionally suitable for multicenter randomized trials. This
      review described and discussed the strategies used and results using viral-based
      vaccines, with emphasis on phases II and III clinical trials. Future directions
      will involve the evaluation of viral-based vaccines in the adjuvant and
      neoadjuvant settings, in patients with low burden metastatic disease, and in
      combination with other forms of therapy including immunotherapy.

PMID- 21952288
TI  - Beyond cancer vaccines: a reason for future optimism with immunomodulatory
      therapy.
AB  - Despite significant scientific knowledge in the field of cancer immunology,
      therapeutic strategies using cancer vaccines to generate anti-tumor immunity have
      historically resulted in only modest clinical benefit. Disappointing results from
      prior cancer vaccine trials are likely due to multifactorial causes. Perhaps the
      most important is the role of inherent tumor-induced immune suppression and
      enhanced immunologic tolerance. Current research directed toward understanding
      the mechanisms of immunologic tolerance has led to the development of promising
      therapeutic immune regulatory antibodies that inhibit immunologic checkpoints and
      subsequently enhance immunologic anti-tumor activity. This review discusses the
      prior challenges associated with cancer vaccines and describes how, by breaking
      immune inhibition and facilitating immune stimulation, immune regulatory
      antibodies show great promise in the treatment of a variety of tumors.

PMID- 21952290
TI  - Vaccines targeting cancer stem cells: are they within reach?
AB  - Increased appreciation of intraclonal heterogeneity of tumors in the past decade
      has led to the resurgence of the cancer stem cell hypothesis. This hypothesis
      also has potential implications for immunologic approaches targeting cancer, and
      it has been suggested that vaccines targeting cancer stem cells may be essential
      for durable antitumor immunity. Recent studies have provided novel insights into
      the nature of antigenic targets expressed on putative cancer stem cells and the
      capacity of both the innate and the adaptive immune system to target these cells,
      as well as the associated challenges. While the phenotypic properties of cancer
      stem cells may be plastic, their stemness and capacity for self-renewal may
      depend on a limited set of genes. Several of these genes overlap with those
      regulating stemness in embryonal stem cells and are also emerging as potential
      oncogenes in some cancers. Immunologic approaches targeting stemness-associated
      pathways in cancer may provide an important strategy for the prevention of
      diverse cancers, including those occurring in the context of regenerative
      therapies.

PMID- 21952289
TI  - Multiple vaccinations: friend or foe.
AB  - Few immunotherapists would accept the concept of a single vaccination inducing a
      therapeutic anticancer immune response in a patient with advanced cancer. But
      what is the evidence to support the "more-is-better" approach of multiple
      vaccinations? Because we are unaware of trials comparing the effect of a single
      vaccine versus multiple vaccinations on patient outcome, we considered that an
      anticancer immune response might provide a surrogate measure of the effectiveness
      of vaccination strategies. Because few large trials include immunologic
      monitoring, the majority of information is gleaned from smaller trials in which
      an evaluation of immune responses to vaccine or tumor, before and at 1 or more
      times following the first vaccine, was performed. In some studies, there is
      convincing evidence that repeated administration of a specific vaccine can
      augment the immune response to antigens contained in the vaccine. In other
      settings, multiple vaccinations can significantly reduce the immune response to 1
      or more targets. Results from 3 large adjuvant vaccine studies support the
      potential detrimental effect of multiple vaccinations as clinical outcomes in the
      control arms were significantly better than that for treatment groups. Recent
      research has provided insights into mechanisms that are likely responsible for
      the reduced responses in the studies noted above, but supporting evidence from
      clinical specimens is generally lacking. Interpretation of these results is
      further complicated by the possibility that the dominant immune response may
      evolve to recognize epitopes not present in the vaccine. Nonetheless, the Food
      and Drug Administration approval of the first therapeutic cancer vaccine and
      recent developments from preclinical models and clinical trials provide a
      substantial basis for optimism and a critical evaluation of cancer vaccine
      strategies.

PMID- 21952291
TI  - Left ventricular noncompaction in a patient with fabry disease: overdiagnosis,
      morphological manifestation of fabry disease or two unrelated rare conditions in
      the same patient?
AB  - We report a clinical case of a young female with Fabry disease but without left
      ventricular hypertrophy, which fulfills the diagnostic criteria of left
      ventricular noncompaction (LVNC). To our knowledge, this is the first report of
      LVNC in a patient with Fabry disease. The possibility of an overdiagnosis of LVNC
      is discussed based on the limitations of the current diagnostic criteria. This
      case was further investigated by genetic analysis, which came to demonstrate the
      limited usefulness of genetic testing in the diagnosis of LVNC. Assuming a true
      trabecular pattern of LVNC, the hypothesis that the same patient has two
      unrelated and rare conditions, although possible, is unlikely. The genetic and
      clinical heterogeneity of LVNC is discussed and supports, along with this
      clinical case, the hypothesis that LVNC is a morphological expression of
      different diseases rather than a distinct cardiomyopathy. Accordingly, LVNC could
      be a rare cardiac manifestation of Fabry disease.

PMID- 21952292
TI  - The biologics anakinra and etanercept prevent cytokine-induced growth retardation
      in cultured fetal rat metatarsal bones.
AB  - BACKGROUND/AIMS: Chronic inflammation during childhood often leads to impaired
      bone growth and reduced adult height. Proinflammatory cytokines interleukin (IL)
      1beta and tumor necrosis factor (TNF)-alpha synergistically impair bone growth in
      vitro. We hypothesized that biologic agents may rescue bones from cytokine
      induced growth impairment and that insulin growth factor (IGF)-I may potentiate
      such an effect. METHODOLOGY: Metatarsal bones from fetal Sprague-Dawley rats (19
      20 days p.c.) were treated with IL-1beta plus TNF-alpha, or the combination of
      these cytokines with anakinra (IL-1 receptor antagonist), etanercept (TNF
      inhibitor) and/or IGF-I. The bones were measured and growth expressed as percent
      increase in bone length over the 7-day culture period. RESULTS: When exposed to
      IL-1beta plus TNF-alpha (10 + 10 ng/ml), bone growth was markedly suppressed (6.6
      +/- 1.4 vs. 50.6 +/- 2.5% in control bones; p < 0.001). The growth of cytokine
      exposed bones (IL-1beta plus TNF-alpha) was dose-dependently rescued by anakinra
      (0.05-500 MUg/ml) or etanercept (0.5-500 MUg/ml); at the highest concentrations,
      growth was similar as in control bones never exposed to cytokines. Also when
      combining IGF-I (100 ng/ml) and relatively low concentrations of anakinra (0.05
      MUg/ml) or etanercept (5 MUg/ml), growth was rescued in an additive way.
      CONCLUSION: Etanercept and anakinra efficiently and dose-dependently prevent
      cytokine-induced bone growth impairment, and combination with IGF-I further
      improves bone growth.

PMID- 21952294
TI  - 2D assembly of non-interacting magnetic iron oxide nanoparticles via"click"
      chemistry.
AB  - Azide-terminated magnetic iron oxide nanoparticles have been assembled in 2D on
      alkyne-terminated self-assembled monolayers (SAMs) by the copper(i) catalyzed
      alkyne-azide cycloaddition (CuAAC) "click" reaction; the kinetics of the reaction
      is an important parameter to control the interparticle distance and thus the
      dipolar interactions.

PMID- 21952295
TI  - The effect of globalization on employee psychological health and job satisfaction
      in Malaysian workplaces.
AB  - OBJECTIVE: To examine the impact of globalization on employee psychological
      health and job satisfaction via job characteristics (i.e., job demands and job
      resources) in an emerging economy, that of Malaysia. As external factors are
      regarded as influences on the working environment, we hypothesized that global
      forces (increased pressure and competition) would have an impact on burnout and
      job satisfaction via increased demands (role conflict, emotional demands) and
      reduced resources (supervisor support, coworkers support). METHODS: Data were
      collected using a population based survey among 308 employees in the state of
      Selangor, Malaysia. Participants were approached at home during the weekend or on
      days off from work. Only one participant was selected per household. Structural
      equation modelling was used to analyse the data. Nearly 54% of respondents agreed
      that they need to work harder, 25% agreed that their job was not secure and 24%
      thought they had lost power and control on the job due to global trade
      competition. RESULTS: Consistent with our predictions, demands mediated the
      globalization to burnout relationship, and resources mediated the globalization
      to job satisfaction relationship. CONCLUSIONS: Together, these results support
      the idea that external factors influence work conditions and in turn employee
      health and job satisfaction. We conclude that the jobs demands-resources
      framework is applicable in an Eastern setting and that globalization is a key
      antecedent of working environments.

PMID- 21952296
TI  - Noise and health--sleep disturbance in adults.
AB  - Factors modifying the effect of environmental noise on sleep include sex, age,
      susceptibility, personality and the health status, including past and present
      history of disease. OBJECTIVE: The effects of noise on sleep and habituation of
      sleep to noise were summarized. RESULTS AND CONCLUSIONS: 1) The effect of noise
      on sleep is associated with physical changes, such as changes in heart rate,
      blood flow volume, breathing and the immune and neurocirculatory systems. During
      sleep, specific changes in these indicators are noted during different sleep
      stages. There are individual and sex differences, and it is important to
      understand the effects of noise on sleep considering several related factors. 2)
      Habituation to noise is also an important phenomenon that must be addressed while
      considering the effects of noise on sleep. Habituation is dependent on the type
      and sound level of the noise. In occupational fields, shift work and job stress
      should be considered to determine the association between noise and sleep, which
      is important to retaining a good quality of working life.

PMID- 21952297
TI  - Occupational violence at Lebanese emergency departments: prevalence,
      characteristics and associated factors.
AB  - BACKGROUND: Emergency departments (EDs) workers are at increased risk of exposure
      to occupational violence. The prevalence of occupational violence is potentially
      higher and consequences are more serious in areas with poor security conditions.
      OBJECTIVES: We investigated the prevalence, characteristics and factors
      associated with the exposure of ED workers to violence at Lebanese hospitals.
      METHODS: All ED employees at six tertiary hospitals in Lebanon were surveyed
      using a cross-sectional design. The survey instrument included four sections
      collecting demographic/professional information and measuring exposure to
      violence, degree of job satisfaction and degree of professional burnout. The
      questionnaire was distributed to all ED employees at participating hospitals and
      was completed by 256 ED workers (70.3% response rate). Multinomial and binary
      logistic regressions were used to investigate factors significantly associated
      with verbal and physical violence. RESULTS: Over the past 12 mo, four in five ED
      employees were verbally abused and one in four was physically assaulted. Exposure
      to verbal abuse was associated with serious outcomes including significantly
      higher levels of occupational burnout and an increased likelihood to quit current
      job. Exposure to physical violence was associated with increased likelihood-to
      quit, nurse status and "public hospital" employment. CONCLUSION: Violence largely
      prevails at Lebanese EDs. Most vulnerable are nurses and employees of public
      hospitals who are disproportionally exposed to violence. ED stakeholders must
      work collaboratively to investigate the root causes of violence and devise and
      implement effective antiviolence policies and measures. Such measures will be
      necessary to protect the well-being and decrease the turnover of ED workers.

PMID- 21952298
TI  - Effect of simvastatin on expression of transforming growth factor-beta and
      collagen type IV in rat mesangial cells.
AB  - OBJECTIVE: Diabetic nephropathy is characterized by the accumulation of
      extracellular matrix in the glomerular mesangium as a result of an imbalance
      between matrix synthesis and degradation. Since simvastatin has been proposed to
      decrease renal interstitial fibrosis, we hypothesized that the protective effect
      of statins was related to the expression of transforming growth factor-beta (TGF
      beta) and type IV collagen (Col IV). METHODS: Cultured rat mesangial cells (RMC)
      were exposed to high glucose (HG), advanced glycosylation end products (AGE) or
      H(2)O(2) in the absence and presence of simvastatin. Expression of TGF-beta and
      Col IV was determined by Western blotting. RESULTS: Coincubation of RMC with HG,
      AGE or H(2)O(2) resulted in a significant increase of the expression of TGF-beta
      and Col IV (p < 0.05). Simvastatin significantly inhibited HG-, AGE- or H(2)O(2)
      induced expression of TGF-beta and Col IV (p < 0.05). Moreover, simvastatin also
      inhibited HG-, AGE- and H(2)O(2)-induced activation of p38 mitogen-activated
      protein kinase, which indicated that the preventive effect of simvastatin on TGF
      beta and Col IV may be associated with p38. CONCLUSION: These findings suggest
      that simvastatin can reduce HG-, AGE- and H(2)O(2)-induced expression of TGF-beta
      and Col IV by inhibition of the p38 pathway.

PMID- 21952299
TI  - Chromatin: Chromatin state reaches out.

PMID- 21952301
TI  - Deconstructing the cell cycle.

PMID- 21952302
TI  - Lanthanide complexes of DOTA monoamide derivatives bearing an isophthalate
      pendent arm.
AB  - An isophthalate-bearing DOTA monoamide derivative has been synthesised and used
      to prepare a family of lanthanide complexes. Luminescence and NMR studies in
      solution show that the predominant form of the complexes in solution is a mono
      capped square antiprism about the lanthanide centre, in which a solvent molecule
      occupies the ninth coordination site. The crystal structure of the terbium
      complex is presented and is in close agreement with the solution state data.

PMID- 21952300
TI  - Forming functional fat: a growing understanding of adipocyte differentiation.
AB  - Adipose tissue, which is primarily composed of adipocytes, is crucial for
      maintaining energy and metabolic homeostasis. Adipogenesis is thought to occur in
      two stages: commitment of mesenchymal stem cells to a preadipocyte fate and
      terminal differentiation. Cell shape and extracellular matrix remodelling have
      recently been found to regulate preadipocyte commitment and competency by
      modulating WNT and RHO-family GTPase signalling cascades. Adipogenic stimuli
      induce terminal differentiation in committed preadipocytes through the epigenomic
      activation of peroxisome proliferator-activated receptor-gamma (PPARgamma). The
      coordination of PPARgamma with CCAAT/enhancer-binding protein (C/EBP)
      transcription factors maintains adipocyte gene expression. Improving our
      understanding of these mechanisms may allow us to identify therapeutic targets
      against metabolic diseases that are rapidly becoming epidemic globally.

PMID- 21952303
TI  - Customizing preoperative fasting protocols to reduce ischemia/reperfusion injury.

PMID- 21952304
TI  - The dual role of epithelial-to-mesenchymal transition in chronic allograft injury
      in pediatric renal transplantation.
AB  - BACKGROUND: Tubulointerstitial damage (TID) is a key feature of chronic allograft
      injury (CAI) and loss. One proposed mechanism attributing to TID is epithelial-to
      mesenchymal transition (EMT); however, it has recently been shown to be unrelated
      to early TID in adult renal allografts. This has yet to be studied in late TID or
      in pediatric renal transplantation; both questions were investigated. METHODS: By
      using 83 unique pediatric renal transplant recipients, 126 protocol, serial,
      posttransplant renal biopsies were examined by centralized, blinded Banff grading
      for CAI and transcriptional profiling (AffyU133+2.0) at 3 (n=20), 6 (n=45), 12
      (n=19), and 24 months (n=42). Two hundred forty-three EMT-associated genes,
      identified from the literature, were interrogated for their differential
      expression in biopsies with and without CAI, using standard bioinformatic
      algorithms. RESULTS: Early (3-6 months) enrichment of EMT (P<=0.05) related gene
      expression was noted, correlating with inflammation in the graft (total i
      scores), with upregulation of hepatocyte growth factor at 24 months, indicating a
      time-dependent mechanism of action. We observed a strong correlation of EMT
      related gene expression with early interstitial fibrosis (r<0.45) for size
      mismatched allograft recipients. Throughout 24 months posttransplant, EMT
      signaling and epithelial-mesenchymal-epithelial cycling were associated with
      progressive CAI injury, with the greatest risk factors being ischemia, immune
      burden, and the calcineurin inhibitor toxicity score. CONCLUSIONS: EMT has a role
      in the evolution of CAI in pediatric transplantation. We postulate that EMT
      dysregulation plays a dual role in fibrosis/injury repair and healing. The
      evolution of this chronic injury response stems from size- mismatched transplant
      ischemia, calcineurin inhibitor nephrotoxicity, and inflammatory response within
      the allograft.

PMID- 21952305
TI  - Corneal transplantation: changing techniques.

PMID- 21952307
TI  - Establishing new porcine ischemic cardiomyopathy model by transcatheter ischemia
      reperfusion of the entire left coronary artery system for preclinical
      experimental studies.

PMID- 21952309
TI  - Dynamic instability of central airways and peripheral airspace in rat lungs
      perfused with cold preservation solutions.
AB  - BACKGROUND/AIMS: For lung preservation, one of two types of solutions is commonly
      employed: Euro-Collins (EC) or low potassium dextran glucose (LPDG). These two
      solutions have been compared regarding biological, morphometrical and
      physiological outcomes in many experiments. However, the dynamic mechanics of
      perfused lung are not well understood because the dynamic characteristics cannot
      be assessed under static conditions; hence, the primary goal of the present study
      was to assess this in perfused rat lungs during the preservation period,
      comparing EC with LPDG at 0 or 9 h at 4 degrees C. METHODS: Lung impedance was
      measured using a forced oscillation technique. Lung resistance and elastance
      values were obtained by the fast Fourier transform algorithm. The instability of
      central airways and heterogeneity of ventilation were estimated. RESULTS: In the
      EC group, airway resistance and instability were high after perfusion, and the
      lung elastance was high and more heterogeneous after cold storage. In contrast,
      those parameters were stable in the LPDG group during cold storage. CONCLUSION:
      Such dynamic stability might facilitate the handling of lung grafts and eliminate
      injurious cyclic ventilation stress after reperfusion. Thus, we conclude that the
      impedance frequency characteristic represents a novel informative parameter for
      investigating lung preservation techniques.

PMID- 21952308
TI  - Plasmonically active micron-sized beads for integrated solid-phase synthesis and
      label-free SERS analysis.
AB  - Self-assembly of gold nanospheres with a very thin glass shell onto the surface
      of beads yields a plasmonically active micron-sized substrate for integrated
      solid-phase synthesis and label-free SERS analysis. The proof-of-principle of
      this approach is demonstrated by the vibrational spectroscopic discrimination of
      three distinct amino acids and a dipeptide.

PMID- 21952310
TI  - Forthcoming Lab on a Chip tutorial series on acoustofluidics: acoustofluidics
      exploiting ultrasonic standing wave forces and acoustic streaming in microfluidic
      systems for cell and particle manipulation.

PMID- 21952312
TI  - Sunlight-induced efficient and selective photocatalytic benzene oxidation on TiO2
      supported gold nanoparticles under CO2 atmosphere.
AB  - The sunlight-induced photocatalytic oxidation of aqueous benzene on TiO(2)
      supported gold nanoparticles was considerably improved when the reaction was
      conducted under a CO(2) atmosphere. 13% yield and 89% selectivity of phenol was
      obtained on P25-supported gold nanoparticles under 230 kPa of CO(2).

PMID- 21952313
TI  - How can we overcome tumor hypoxia in radiation therapy?
AB  - Local recurrence and distant metastasis frequently occur after radiation therapy
      for cancer and can be fatal. Evidence obtained from radiochemical and
      radiobiological studies has revealed these problems to be caused, at least in
      part, by a tumor-specific microenvironment, hypoxia. Moreover, a transcription
      factor, hypoxia-inducible factor 1 (HIF-1), was identified as pivotal to hypoxia
      mediated radioresistance. To overcome the problems, radiation oncologists have
      recently obtained powerful tools, such as "simultaneous integrated boost
      intensity-modulated radiation therapy (SIB-IMRT), which enables a booster dose of
      radiation to be delivered to small target fractions in a malignant tumor",
      "hypoxia-selective cytotoxins/drugs", and "HIF-1 inhibitors" etc. In order to
      fully exploit these innovative and interdisciplinary strategies in cancer
      therapy, it is critical to unveil the characteristics, intratumoral localization,
      and dynamics of hypoxia/HIF-1-active tumor cells during tumor growth and after
      radiation therapy. We have performed optical imaging experiments using tumor
      bearing mice and revealed that the locations of HIF-1-active tumor cells changes
      dramatically as tumors grow. Moreover, HIF-1 activity changes markedly after
      radiation therapy. This review overviews 1) fundamental problems surrounding
      tumor hypoxia in current radiation therapy, 2) the function of HIF-1 in tumor
      radioresistance, 3) the dynamics of hypoxic tumor cells during tumor growth and
      after radiation therapy, and 4) how we should overcome the difficulties with
      radiation therapy using innovative interdisciplinary technologies.

PMID- 21952315
TI  - Hepatic regeneration after sublethal partial liver irradiation in cirrhotic rats.
AB  - Our previous animal study had demonstrated that partial liver irradiation (IR)
      could stimulate regeneration in the protected liver, which supported the
      measurements adopted in radiotherapy planning for hepatocellular carcinoma. The
      purpose of this present study is to investigate whether cirrhotic liver
      repopulation could be triggered by partial liver IR. The cirrhosis was induced by
      thioacetamide (TAA) in rats. After cirrhosis establishment, TAA was withdrawn. In
      Experiment 1, only right-half liver was irradiated with single doses of 5 Gy, 10
      Gy and 15 Gy, respectively. In Experiment 2, right-half liver was irradiated to
      15 Gy, and the left-half to 2.5 Gy, 5 Gy and 7.5 Gy, respectively. The
      regeneration endpoints, including liver index (LI); mitotic index (MI); liver
      proliferation index (LPI); PCNA-labeling index (PCNA-LI); serum HGF, VEGF, TGF
      alpha and IL-6, were evaluated on 0 day, 30-day, 60-day, 90-day, 120-day and 150
      day after IR. Serum and in situ TGF-beta1 were also measured. In both
      experimental groups, the IR injuries were sublethal, inducing no more than 9%
      animal deaths. Upon TAA withdrawal, hepatic regeneration decelerated in the
      controls. In Experiment 1 except for LI, all other regeneration parameters were
      significantly higher than those in controls for both right-half and left-half
      livers. In Experiment 2 all regeneration parameters were also higher compared
      with those in controls for both half livers. Serum HGF and VEGF were increased
      compared with that of controls. Both unirradiated and low dose-irradiated
      cirrhotic liver were able to regenerate triggered by sublethal partial liver IR
      and higher doses and IR to both halves liver triggered a more enhanced
      regeneration.

PMID- 21952314
TI  - Radioprotection of sensitive rat tissues by oligoelements Se, Zn, Mn plus
      Lachesis muta venom.
AB  - In this study we first evaluated the general radioprotective efficacy of Se, Zn
      and Mn (4 ug/ml each) plus Lachesis muta venom (4 ng/ml) combination (O-LM) by
      determining survival on rats irradiated with lethal doses of gamma-rays. The aim
      of the second part of the study was to investigate the O-LM ability to prevent
      ionizing radiation-induced damage on small intestine, bone marrow and
      submandibular glands. Hence, histological characteristics and functional studies,
      together with proliferation and apoptotic marker levels on whole body irradiated
      rats with a 5 Gy dose were evaluated. Results show that all animals of the
      untreated group died after whole body irradiation with 8 and 10 Gy while 60 day
      survival was more than 80% and 40% in O-LM-treated animals, respectively.
      Histopathological examinations revealed a high degree of small intestine and
      submandibular gland radioprotection 3 days post-irradiation. O-LM inhibited
      histological damage on small intestine, restoring the radiation-induced reduction
      in villous height and crypt number. O-LM prevented radiation-induced loss of
      salivary gland function and morphological alterations. These effects were
      associated to a complete inhibition of radiation-induced apoptosis. Furthermore,
      studies performed 30 days post-irradiation revealed that O-LM significantly
      improved bone marrow repopulation, increasing all medullar progenies to the
      extent of the non-irradiated animals, and completely prevented permanent
      submandibular gland alterations. Based on the present results and taking into
      account that O-LM is being safely administered in phase I clinical trial as an
      immunomodulator, we conclude that O-LM is a non-toxic promising approach to
      achieve radioprotection for patients undergoing radiotherapy.

PMID- 21952316
TI  - The effect of vitamin D prophylaxis on radiation induced pulmonary damage.
AB  - Vitamin D has a selective radio and chemosensitizing effect on tumor cells. In
      vitro and in vivo studies have shown that vitamin D inhibits collagen gel
      construction, induces type II pneumocyte proliferation and surfactant synthesis
      in the lungs, and decreases vascular permeability caused by radiation. The aim of
      this experimental study was to determine if vitamin D has a protective effect
      against radiation-induced pulmonary damage. Adult Wistar rats were divided into 4
      groups. Group 1 was comprised of control animals. Group 2, which was administered
      0.25 ug/kg/day of vitamin D3 for 8 weeks, was the vitamin D control group. Rats
      in groups 3 and 4 were given 20 Gy right hemithorax radiotherapy, and in addition
      group 4 was given vitamin D3 treatment, which began the day before the
      radiotherapy and continued for 8 weeks. At the 8(th) and the 12(th) weeks of the
      study 4 rats from each group were sacrificed. Right lungs were dissected for
      light and electron microscopic study. The electron microscopy examinations
      revealed statistically significant differences between group 3 and 4, and in
      group 4 there was less interstitial inflammation and collagen deposition, and the
      alveolar structure and the cells lining the alveolar walls were protected. These
      results confirm that vitamin D has a protective effect against radiation-induced
      pulmonary toxicity. These findings should be evaluated with further clinical
      studies.

PMID- 21952317
TI  - Hydrogen sulfide contributes to hypoxia-induced radioresistance on hepatoma
      cells.
AB  - Growing evidence has demonstrated that, as an endogenous signaling
      gasotransmitter, hydrogen sulfide (H(2)S) plays an important role in regulating
      numerous biological functions. The role of H(2)S in hypoxia-induced
      radioresistance on hepatoma cells was investigated in the present work. Results
      showed that, when HepG2 cells were maintained in hypoxia circumstances for 4 h,
      the cellular radioresistance was extensively increased so that the oxygen
      enhancement ratio of the survival fraction approached 2.68. Under this hypoxic
      condition, when the cells were treated with DL-propargylglycine (PPG) and
      aminooxyacetic acid (AOAA), a specific inhibitor of H(2)S synthase of
      cystathionine-gamma-lyase (CSE) and cystathionine-beta-synthase (CBS)
      respectively, radiation responses including cell killing, micronuclei (MN)
      formation, and caspase-3 activity were significantly enhanced. However, treatment
      of cells with low concentrations of NaHS (<= 100 uM) protected cells from these
      radiation damages. Western bolting assay showed that CSE and CBS were over
      expressed in the irradiated hypoxic cells in a dose dependent manner. Moreover,
      when the hypoxic HepG2 cells were treated with NaHS together with glibenclamide,
      a specific inhibitor of K(+)(ATP) channels, the role of exogenous H(2)S in
      radioprotection was partly eliminated. This study demonstrated that H(2)S
      contributed to hypoxia-induced radioresistance probably via the opening of
      K(+)(ATP) channels, which suggests that the endogenous H(2)S synthase could be a
      potential radiotherapeutic target for a hypoxic tumor.

PMID- 21952318
TI  - Screening for 137Cs body burden due to the Chernobyl accident in Korosten City,
      Zhitomir, Ukraine: 1996-2008.
AB  - During the Chernobyl Nuclear Power Plant (CNPP) accident on 26 April 1986, large
      amounts of radionuclides were released and spread to vast areas. Inhabitants
      residing around CNPP have been exposed to external and internal irradiation due
      to the long half-life of (137)Cs (30 years). In this study, we screened for
      internal whole-body (137)Cs concentration using a whole-body counter in the
      Zhitomir state of Ukraine. The total number of participants was 144,972 (96,149
      females and 48,823 males). The median body burden of (137)Cs per body weight
      decreased from 1996 to 2008. In particular, after 2003, more than half of
      subjects had internal exposure doses below the detectable level. A weak seasonal
      effect was found in measurement data from 1997 to 1999, but no such effects were
      observed in later years. We also calculated annual dose for each year and
      confirmed that doses have been decreasing gradually. In particular, after 2003,
      the annual effective dose decreased to 0.1 mSv y(-1) for 95% of the participants.
      Only two persons were found to have received more than 5 mSv y(-1) since 2007.
      Although the health effects of (137)Cs body burden due to the Chernobyl accident
      remain uncertain, further screening is needed to monitor the health status and to
      allay the anxiety of inhabitants in the contaminated areas around CNPP.

PMID- 21952319
TI  - Preliminary results of conformal computed tomography (CT)-based intracavitary
      brachytherapy (ICBT) for locally advanced cervical cancer: a single institution's
      experience.
AB  - Intracavitary brachytherapy using tandem and ovoids is an important component of
      definitive treatment for cervical cancer. In the present study, we analyzed the
      dose-volume histograms (DVHs) of the tumor volume and organs at risk including
      the sigmoid colon by CT-based treatment planning for high dose rate (HDR)
      intracavitary brachytherapy (ICBT) in cervical cancer. Seventeen patients with
      carcinoma of the cervix uteri were treated with external beam radiotherapy plus
      concurrent chemotherapy. For brachytherapy, the planning procedure started by
      performing a conventional plan which prescribed a dose of 6.5-7 Gy per fraction
      to point A, then optimized the dose based on CT imaging. Volumes and DVHs were
      calculated for the HR-CTV, bladder, rectum and sigmoid colon. The mean BED(2Gy)
      total doses of post-optimized plans of HR-CTV, bladder, rectum and sigmoid colon
      were: 89.6, 94.1, 74.0 and 69.8 Gy, respectively. For conventional plans, the
      calculated mean BED(2Gy) total doses of HR-CTV, bladder, rectum and sigmoid colon
      were 92.2, 120.1, 75.7 and 78.3 Gy, respectively. This study showed statistical
      significant higher BED(2Gy) total doses for bladder and sigmoid colon (p < 0.001)
      using conventional plans versus post-optimized, CT-based plans, while no
      difference between HR-CTV and rectum BED(2Gy) total doses could be detected.
      After a median follow-up of nineteen months, all seventeen patients had a
      clinical complete response. Two patients developed distant metastasis. Compared
      with conventional treatment, CT based brachytherapy planning was very effective
      in reducing doses to OARs, especially bladder and sigmoid colon whilst
      maintaining a high therapeutic dose for tumor target volumes in the treatment of
      cervical carcinoma.

PMID- 21952320
TI  - A novel combination treatment of armed oncolytic adenovirus expressing IL-12 and
      GM-CSF with radiotherapy in murine hepatocarcinoma.
AB  - In this study, a novel combination treatment of armed oncolytic adenovirus
      expressing interleukin 12 (IL-12) and granulocyte-macrophage colony-stimulating
      factor (GM-CSF) with radiation was investigated for antitumor and antimetastatic
      effect in a murine hepatic cancer (HCa-I) model. Tumor bearing syngeneic mice
      were treated with radiation, armed oncolytic virus Ad-DeltaE1Bmt7 (dB7)
      expressing both IL-12 and GM-CSF (armed dB7), or a combination of both. The
      adenovirus was administered by intratumoral injection 1 * 10(8) PFU per tumor in
      50 ul of PBS four times every other day. Tumor response to treatment was
      determined by a tumor growth delay assay. Metastatic potential was evaluated by a
      lung metastasis model. To understand the underlying mechanism, the level of
      apoptosis was examined as well as the change in microvessel density and
      expression of immunological markers: CD4+, CD8+ and Cd11c. The combination of
      armed dB7 and radiation resulted in significant growth delay of murine hepatic
      cancer, HCa-1, with an enhancement factor of 4.3. The combination treatment also
      resulted in significant suppression of lung metastasis. Increase of apoptosis
      level as well as decrease of microvessel density was shown in the combination
      treatment, suggesting an underlying mechanism for the enhancement of antitumor
      effect. Expression of immunological markers: CD4+, CD8+ and Cd11c also increased
      in the combination treatment. This study showed that a novel combination
      treatment of radiotherapy with armed oncolytic adenovirus expressing IL-12 and GM
      CSF was effective in suppressing primary tumor growth.

PMID- 21952321
TI  - Silent cardiac ischemia after an ischemic stroke of the right hemisphere.
AB  - A patient is described who previously had daily complaints of angina pectoris,
      yet no longer experienced chest pain after an ischemic stroke of the right
      hemisphere, despite several recorded episodes of electrocardiographic changes and
      an elevation of cardiac enzymes compatible with myocardial ischemia. The
      cingulate gyrus is involved in spatial attention and neglect, and is, according
      to positron emission tomography studies, less activated in silent myocardial
      ischemia. We suggest that this patient was not aware of the angina because of
      putamen ischemia and secondary disturbed projection to the cingulate gyrus and no
      longer felt or experienced this referred pain.

PMID- 21952322
TI  - High sensitive trap loss spectroscopic detection of the lowest vibrational levels
      of ultracold molecules.
AB  - We present a controllable three-dimensional fluorescence modulation technique for
      the high sensitive trap loss detection of ultracold molecules. The lowest
      vibrational levels (v = 0 and 1) of the pure long-range state 0(-)(g) (6S(1/2) +
      6P(3/2)) of a cesium molecule are detected directly with high rotational
      resolution. Our technique proved to be a robust tool for effectively improving
      the detection sensitivity of trap loss spectroscopy.

PMID- 21952323
TI  - Chromogenic and fluorogenic detection of a nerve agent simulant with a rhodamine
      deoxylactam based sensor.
AB  - A chromogenic and fluorogenic detection of a nerve agent simulant was developed
      based on diethyl chlorophosphate triggered tandem phosphorylation and
      intramolecular cyclization of N-(rhodamine B)-deoxylactam-2-aminoethanol.

PMID- 21952324
TI  - Thin bronchoscope for evaluating stenotic airways during stenting procedures.
AB  - BACKGROUND: Flexible bronchoscopy can play an important role in the evaluation of
      an airway lumen during therapeutic bronchoscopic procedures. Despite its
      potential usefulness, however, evaluation with a standard-sized bronchoscope,
      which cannot pass completely through a severely stenosed airway, is often
      unsatisfactory. OBJECTIVES: This study aimed to evaluate the usefulness of
      prototype thin bronchoscopes for assessing stenotic airways during stenting
      procedures. METHODS: Forty-six patients with central airway stenosis requiring
      stent implantation were enrolled in this prospective study. After inserting a
      rigid bronchoscope under general anesthesia, a flexible bronchoscopic evaluation
      using a 5.9- or 6.0-mm standard bronchoscope was performed, followed by
      evaluation using a prototype 3.4- or 3.5-mm thin bronchoscope for airways beyond
      the site of stenosis, which could not be visualized by the standard bronchoscope.
      RESULTS: A standard bronchoscope could not pass through the stenotic airway in 15
      of 46 patients (33%). On univariate analysis, the grade of stenosis (p < 0.001),
      the presence or absence of atelectasis (p = 0.04) and the presence or absence of
      viscous secretions (p = 0.02) were related to the rate of successful passage by a
      standard bronchoscope. On multivariate analysis, only the grade of stenosis
      remained independently associated with the success rate. In 12 of the 15 patients
      (80%), the airway lumen beyond the stenotic lesion, which could not be reached by
      a standard bronchoscope, was successfully visualized and evaluated with a thin
      bronchoscope. No significant complications were associated with the procedures.
      CONCLUSION: The thin bronchoscope can be a useful tool for evaluating a severely
      stenosed airway during the stenting procedure.

PMID- 21952325
TI  - What is high quality critical care?

PMID- 21952326
TI  - Aiming for zero: decreasing central line associated bacteraemia in the intensive
      care unit.
AB  - AIM: To eliminate Central Line Associated Bacteraemia (CLAB) in the Critical Care
      Complex (CCC)-Intensive Care Unit (ICU) and High Dependency Unit (HDU)-Middlemore
      Hospital. METHOD: Multifaceted quality improvement programme that included:
      engagement with ICU leadership and education of ICU staff; the introduction of a
      CLAB prevention bundle of care through standardised checklists for central line
      insertion (December 2008) and line maintenance (July 2009); the development of a
      central line pack; and rapid, visual feedback of results. RESULTS: Absolute
      numbers of CLAB in the CCC decreased from 14 in 2008, to 4 in 2009 and 1 in the
      first 6 months of 2010 (despite increase in bed census and a doubling of
      admissions). The CLAB rate per 1,000 line days decreased from 6.6 to 0.9. The
      days between CLAB increased from a median of 30 to >100 days, with zero CLAB for
      5 of the last 6 months. Mortality for patients with CLAB was 37%, compared with
      mortality of 13% for all other ICU patients. The conservative cost savings were
      $200,000 in 2009 and $260,000 in 2010. CONCLUSION: Using an evidenced-based
      quality improvement approach, it is possible to significantly decrease Central
      Line Associated Bacteraemia in the Critical Care Complex. In doing so patient
      morbidity and mortality are reduced and money is saved for other healthcare
      needs.

PMID- 21952327
TI  - Why Maori women continue to smoke while pregnant.
AB  - AIM: To investigate why some Maori women continue smoking during pregnancy.
      METHODS: An exploratory qualitative study was conducted with 60 pregnant Maori
      women aged from 17-43. A questionnaire was used to guide the interviews.
      Responses were categorised using Te Whare Tapa Wha (the four-sided house), an
      Indigenous theoretical framework. RESULTS: The women smoked on average 9
      cigarettes per day. Many (45%) were very concerned for their baby's health. The
      main reasons for quitting were for their own and their baby's health. The
      majority (77%) reported no smoking-related health problems. All the women lived
      with at least one other smoker. Over half of the participants (62%) predominantly
      socialised with people who smoked and nearly all said it was easy to smoke in
      their socialising and work environments. Partners and mothers were the most
      common source of support or advice to quit, however, often that support person
      also smoked. There was a lack of understanding of the harms associated with
      maternal smoking. CONCLUSIONS: Motivation to quit smoking was low. The women all
      lived with smokers which reportedly made it harder to quit; most of them lived in
      a smoky environment, where family, friends and coworkers smoked. This highlights
      the need to include family in cessation interventions.

PMID- 21952328
TI  - Post-caesarean section surgical site infection: rate and risk factors.
AB  - AIM: To identify the incidence of surgical site infection (SSI) post-caesarean
      section, and important contributory risk factors. METHOD: A retrospective
      analysis was conducted to identify cases with SSI, using as a population all the
      caesarean sections for the 6-month period from 16 March 2009-15 September 2009
      performed at Waikato Hospital (n=526). Cases (n=25) were compared with randomly
      selected controls (n=50) to identify important risk factors. RESULTS: In total,
      25 of the 526 patients (5%) had a SSI post-caesarean section. Of these, 15 were
      revealed during the initial admission (3%), and the other 10 required hospital
      care post-discharge for treatment of infection (2%). The key risk factors for
      surgical site infection post-caesarean section identified were elevated BMI,
      longer duration of labour, and having an emergency procedure. CONCLUSION: This
      study has identified significant risk factors for surgical site infection post
      caesarean section. Identification of these risk factors reminds obstetric staff
      that appropriate targeting of infection reducing strategies to women at high risk
      is needed.

PMID- 21952329
TI  - Self-reported oral health care and access to oral health information among
      pregnant women in Wellington, New Zealand.
AB  - OBJECTIVES: The aims of this study were to gain an understanding of pregnant
      women's oral health care practices, access to information, and dental care usage
      in New Zealand, and to investigate whether these differed between
      sociodemographic groups. METHODS: One researcher visited 69 antenatal classes in
      the Wellington region to explain the study. Women self-completed the
      questionnaire and returned it by post. RESULTS: A total of 405 women (55%
      response rate) took part. 79.2% of participants identified as New Zealand
      European and most were of high income and education levels, 32% visited the
      dentist during pregnancy and more than 60% reported bleeding gums. Women with a
      household income under NZ$70,000 per year were significantly less likely to
      report access to oral health information (OR 0.27, 95%CI 0.10-0.76) and more
      likely to report the need to see a dentist (OR 2.55, 95%CI 1.08-5.99) compared to
      women with an income over NZ$100,000 per year. CONCLUSIONS: Visits to the dentist
      and access to oral health information were more common among New Zealand European
      women with higher education achievements and higher socioeconomic backgrounds
      with only a third of women went seeing a dentist during pregnancy. Improving the
      oral health of pregnant women will have follow-on benefits of improved oral
      health outcomes for their children.

PMID- 21952330
TI  - Impact of the human papillomavirus (HPV) vaccine on genital wart diagnoses at
      Auckland Sexual Health Services.
AB  - AIM: To review cases of genital warts diagnosed at Auckland Sexual Health Service
      (ASHS) and to document any change following the introduction of the human
      papillomavirus (HPV) vaccination. The national HPV immunisation programme, using
      the quadrivalent vaccine Gardasil, commenced on 1 September 2008. The publically
      funded programme provides for the ongoing vaccination of girls in year 8 with an
      initial catch-up programme for young women born after 1 January 1990 until the
      end of 2010. Monitoring rates of diagnosis of genital warts should provide the
      earliest clinical indicator of a population response to the vaccine. METHOD: The
      proportion of new clients attending ASHS who were diagnosed with genital warts
      from 1 January 2007 to 31 December 2008 was compared to the proportion diagnosed
      from 1 January 2009 to 30 June 2010. RESULTS: 40,793 new clients attended the
      ASHS between 2007 and June 2010 and genital warts were diagnosed in 3125 (7.7%).
      Genital warts were diagnosed in 9.2% of new clients in 2007 decreasing to 6.6%
      for the first 6 months of 2010. Analysis of the subgroup of clients under the age
      of 20 years, found genital warts in males decreased from 11.5% in 2007 to 6.9% in
      2010 while in females the rates decreased from 13.7% to 5.1% over the same time
      period. In comparison, the rates decreased from 7.5% in 2007 to 5.9% in 2010 for
      females aged 20 years and over. Thus there was evidence of a significant
      difference, in the pre to post vaccination era, in the proportion of female
      clinic visits for genital warts in those aged less than 20 years and those aged
      21 years or older (p=0.02) and further a borderline significant difference for
      males aged less than 20 years (p=0.05). CONCLUSION: A significant decline in the
      incidence of genital warts in the target population suggests an early response to
      the HPV vaccination programme with some evidence of an effect for males aged less
      than 20 years.

PMID- 21952331
TI  - Terminations of pregnancy associated with isotretinoin use in New Zealand.
AB  - AIMS: Oral isotretinoin is a highly-effective treatment for severe acne. It is
      also highly teratogenic. Recently, funded access was widened (from vocationally
      registered dermatologists only) to include vocationally trained general
      practitioners and nurse practitioners acting within their scope of practice. This
      decision has caused some debate. While it is hoped that it will increase access
      to those living in more deprived areas, there are concerns that there will be an
      increase in the number of affected pregnancies. This study aims to report on
      terminations of pregnancy occurring while using isotretinoin in New Zealand.
      METHOD: Using NHI numbers, termination of pregnancy admissions were matched to
      recent isotretinoin prescriptions. RESULTS: This study has revealed that there
      appears to have been more unintended pregnancies related to isotretinoin use than
      previously thought. A total of 39 terminations of pregnancy related to
      isotretinoin use were identified in the year ending June 2008. This gave a crude
      termination of pregnancy rate of 73 per 10,000 females aged 10-44 years.
      CONCLUSIONS: While there are some limitations to this study, the results are
      consistent with recent international research suggesting previous pregnancy rates
      on isotretinoin have been underestimates. Widening funding of isotretinoin will
      likely increase the absolute numbers of pregnancies but also has the potential to
      increase relative numbers. As such, it will be vital that primary care is alert
      to the risks of isotretinoin use and gain experience in its day-to-day usage.
      Although access has been widened, all requests for funding will now be recorded
      on a national database (Special Authority database) to enable closer monitoring
      of isotretinoin usage.

PMID- 21952332
TI  - The role of humans in the importation of ticks to New Zealand: a threat to public
      health and biosecurity.
AB  - Humans coming into New Zealand occasionally, and unwittingly, bring exotic ticks
      with them, either attached to their bodies or with luggage. Of the 172 available
      records for tick interception at New Zealand's border, half can be attributed to
      human agency. Here, together with an outline of tick biology and ecology, we
      present evidence of at least 17 species of ticks being brought in by humans, with
      Australia, North America and Asia the most frequent countries of origin. Risks
      posed by some of the nine species of ticks already in New Zealand are briefly
      examined. Sites of attachment of ticks and associated symptoms where these have
      been recorded are presented. Diseases transmitted by ticks and most likely to be
      encountered by travellers are briefly discussed together with the most practical
      method of tick removal. A plea is made for practitioners to increase their
      awareness of the risks to New Zealand's biosecurity and public health posed by
      ticks and to ensure that as many as possible of these unwelcome 'souvenirs' are
      collected and passed on for identification.

PMID- 21952333
TI  - Improving termination of pregnancy services in New Zealand.
AB  - The aim of this article is to review evidence of the access and timeliness of
      termination of pregnancy (TOP) services to date in New Zealand and to provide
      clinic level and policy recommendations for service improvement. Compared to
      other countries, New Zealand successfully provides access to TOP services
      regardless of ability to pay, yet still lags behind other OECD countries in
      timeliness of services. There are clear differences in the organisational
      structure of clinics around the country, the most striking difference being
      between the private and public sectors. Streamlining referral pathways, expanding
      the availability of medical TOPs, and improving the organisational structure of
      clinics would all contribute to improving the timeliness of services and
      therefore the quality of care received by women. Improvements in the timeliness
      of TOP services in New Zealand are needed and achievable, even without
      legislative changes.

PMID- 21952334
TI  - Sirenomelia.
AB  - Sirenomelia is a rare malformation of caudal part of embryo. It is characterised
      by complete or partial fusion of the legs into a single lower limb. Abnormalities
      of the kidneys, large intestines and genitalia are common. Sirenomelia cases have
      only one umbilical artery and one vein. Upper body birth defects are rare and
      include abnormalities of heart, lungs, arms, spine and brain. Here we report a
      case of sirenomelia with uncommon upper body birth defects involving right
      forearm and hand, and the rib cage. Vascular steal phenomenon cannot explain the
      upper body birth defects.

PMID- 21952335
TI  - Medical image. Intimal intimation.

PMID- 21952336
TI  - A paradigm shift in recreational drug use: the challenge of legal highs in New
      Zealand.

PMID- 21952337
TI  - Seroprevelance study of pandemic strain influenza A H1N1 (pH1N1) in Wellington
      children: the usefulness of testing children in a hospital setting.

PMID- 21952338
TI  - Are healthy people being manipulated into becoming chiropractic clients?

PMID- 21952339
TI  - Colchicine prescribing in patients with gout.

PMID- 21952340
TI  - The "Twin Study" and the misunderstanding of epidemiology that clouds
      occupational associations and low back disorder.

PMID- 21952341
TI  - Spigelian hernia secondary to trauma in an adult patient.

PMID- 21952342
TI  - The obesity pandemic, the diabetes 'tsunami', and the lack of adequate sports
      grounds for children in Auckland, New Zealand.

PMID- 21952343
TI  - Graphene oxide as an efficient signal-to-background enhancer for DNA detection
      with a long range resonance energy transfer strategy.
AB  - A long range resonance energy transfer (LrRET) strategy for label-free and
      sensitive DNA detection is outlined by introducing graphene oxide (GO) as an
      efficient signal-to-background enhancer, giving a limit of determination (3sigma)
      of 0.31 nM.

PMID- 21952345
TI  - Post-thrombotic syndrome patient education based on the health belief model: self
      reported intention to comply with recommendations.
AB  - PURPOSE: This study was designed to evaluate patient responses to a patient
      education handout on post-thrombotic syndrome prevention based on the Health
      Belief Model. DESIGN: This quasi-experimental pilot study involved a patient
      survey to be completed after reviewing a patient education handout. PARTICIPANTS
      AND SETTING: A convenience sample of 25 patients with deep vein thrombosis
      confirmed by venous Doppler assessment with a lower extremity deep vein
      thrombosis admitted to a Midwestern community hospital was identified. Seven
      patients were excluded and 5 declined participation; 13 completed the survey
      patients. Subjects were older than 18 years and able to read and understand
      English. Patients with hospice or palliative care service or life expectancy less
      than 6 months were excluded. METHODS: Subjects were provided with the post
      thrombotic syndrome (PTS), patient education handout, and the PTS patient
      education survey. The PTS patient education handout consisted of a 1-page
      informational sheet based on PTS and Health Belief Model literature. The 24-item
      PTS Patient Education Survey required approximately 15 minutes to complete; items
      included demographic information, questions regarding previous deep vein
      thrombosis and Likert scale opinion statements regarding PTS based on Health
      Belief Model components. Patients meeting inclusion criteria were approached by
      the investigator, invited to participate in the study, and offered the option of
      having the investigator collect the survey or return in an addressed, stamped
      envelope. RESULTS: Respondents tended to agree that PTS was a serious condition
      and that it would negatively affect their life, primarily in relation to comfort
      and the ability to engage in leisure activities. Ten participants (76.9%)
      acknowledged that they were susceptible to PTS, and that elastic graduated
      compression stockings were effective. The most commonly cited barrier to wearing
      the stockings was difficulty with application. Five patients (38.5%) agreed that
      they had the ability to prevent PTS and 9 (69.2%) indicated that they intended to
      wear the stockings. CONCLUSIONS: Patient education for post-thrombotic syndrome
      prevention based on the Health Belief Model resulted in self-reported intention
      to comply with recommendations to wear graduated elastic compression stockings.
      Compliance may be enhanced by specifically addressing individual risk factors and
      barriers to stocking application.

PMID- 21952346
TI  - A 3-in-1 perineal care washcloth impregnated with dimethicone 3% versus water and
      pH neutral soap to prevent and treat incontinence-associated dermatitis: a
      randomized, controlled clinical trial.
AB  - PURPOSE: We compared the effectiveness of a 3-in-1 perineal care washcloth versus
      standard of care (water and pH neutral soap) to prevent and treat incontinence
      associated dermatitis (IAD). The product under study was a soft, premoistened
      washcloth, including a 3% dimethicone formula, with cleansing, moisturizing, and
      barrier protection properties. DESIGN: Randomized, controlled clinical trial.
      SUBJECTS AND SETTING: The study sample comprised a random sample of 11 nursing
      home wards (6 experimental and 5 control) in a convenience sample of 4 nursing
      homes in Belgium. The sample included nursing home residents at risk for and/or
      affected by IAD defined as incontinent of urine, feces, urine/feces, and/or
      having erythema of the perineal skin (not caused by pressure/shear), and/or
      having an edematous skin in the genital area. METHODS: Participants in the
      experimental group were treated according to a standardized protocol, including
      the use of a 3-in-1 perineal care washcloth impregnated with a 3% dimethicone
      skin protectant. Participants in the control group received perineal skin care
      with water and pH neutral soap, the standard of care in Belgian nursing homes.
      The study period was 120 days. Data were collected between February and May 2010.
      Incontinence-associated dermatitis prevalence and severity were assessed using
      the IAD Skin Condition Assessment Tool. The surface (cm), redness, and depth of
      the perineal lesion were assessed daily by the nurses. This tool generates a
      cumulative severity score (maximum score = 10) based on area of skin affected,
      degree of redness, and depth of erosion. RESULTS: Four hundred sixty-four nursing
      home residents were assessed and 32.9% (n = 141) met the criteria for inclusion,
      including 73 subjects in the experimental group and 68 in the control group.
      Baseline IAD prevalence was comparable in both groups (experimental: 22.3% vs
      control: 22.8%, P = .76). Baseline IAD severity was 6.9/10 in the experimental
      group and 7.3/10 in the control group. A significant intervention effect on IAD
      prevalence was found (experimental: 8.1% vs control: 27.1%, F = 3.1, P = .003). A
      nonsignificant effect on IAD severity could be determined (experimental: 3.8/10
      vs control: 6.9/10, F = 0.8, P = .06). CONCLUSION: The use of a 3-in-1 washcloth,
      impregnated with a 3% dimethicone formula, resulted in a significantly reduced
      prevalence of IAD and a trend toward less severe lesions. These findings provide
      indicative evidence for the use of 3-in-1 perineal care washcloth as an effective
      intervention against the use of water and a pH neutral soap to prevent and/or
      treat IAD.

PMID- 21952347
TI  - Issues related to accurate classification of buttocks wounds.
AB  - PURPOSE: This study was designed to determine the level of agreement among wound
      care nurses when asked to classify the etiology of 9 wounds located on the
      buttocks and within the intergluteal cleft. SUBJECTS: Study subjects were 100
      wound care nurses who responded to an invitation placed on the WOCN Society's
      wound care forum and to an e-mail sent to members of the WOCN Iowa Affiliate.
      METHODS: Respondents were asked to view 9 unique wound photos and to determine
      whether the primary etiologic factor was pressure, moisture, incontinence
      associated dermatitis, or skin tear. Subjects were given no background
      information regarding the patients but were allowed to add comments. RESULTS: The
      overall kappa analysis of the 9 photos combined was 0.1708 (99% confidence
      interval, 0.1630-0.1786). The testing of the overall kappa for the 9 photos
      equaling "0" or mere chance produced a P < .0001. Analyses revealed that the
      agreement between the 100 respondents for the 9 photos was only 17% better than
      chance alone. In summary, our study revealed only "Slight Agreement" between
      wound care nurses' classifications of photo subgroups or for all 9 photos
      analyzed together. IMPLICATIONS: Accurate wound classification impacts not only
      treatment decisions but also reimbursement, risk of litigation, and accuracy of
      data regarding prevalence and incidence of pressure ulcers. It is, therefore,
      critical for professional societies such as the WOCN to begin development of
      consensus definitions and guidelines to ensure consistency and accuracy in wound
      classification.

PMID- 21952348
TI  - Predictors of help seeking among Korean American women with urinary incontinence.
AB  - PURPOSE: The purpose of this study was to test an adapted theoretical model to
      predict help-seeking behavior (HSB) for urinary incontinence (UI) among Korean
      American women. SUBJECTS AND SETTINGS: A sample of 149 Korean American women with
      UI was recruited from local religious organizations in Arizona. DESIGN: This
      study uses a cross-sectional correlation descriptive design. METHODS: Respondents
      completed 7 instruments: the HSB, Brief Acculturating Rating Scale of Korean
      American-II, family tradition and authority orientation, incontinence quiz,
      incontinence severity index, incontinence-specific quality of life (QOL), and
      social support tool. Respondents either completed questionnaires or they were
      administered face to face. Descriptive statistics, standardized Cronbach alpha
      coefficients, factor analysis, and hierarchical multiple regression were used to
      analyze data. RESULTS: Thirty-six percent of variance in HSB was explained by
      severity of UI, incontinence-specific QOL, and social support in the proposed
      theoretical framework. Health care support facilitates help seeking among Korean
      American women who have severe UI symptoms and low UI-specific QOL. Social
      support from friends, family, and available information facilitates help seeking
      in this group. CONCLUSION: WOC and continence nurses should take an active role
      to design intervention for Korean American women with UI emphasizing on social
      support from family and friends and available information in Korean.

PMID- 21952349
TI  - Remote ischemic postconditioning: does it protect against ischemic damage in
      percutaneous coronary revascularization? justification and design of a randomized
      placebo-controlled clinical trial.
AB  - OBJECTIVE: Myocardial damage that is associated with percutaneous coronary
      intervention (PCI) partially affects the results of the procedure, and is related
      to medium-term cardiovascular death. Remote postischemic conditioning might
      reduce the myocardial lesions that are associated with PCI, but perhaps less so
      in diabetics. The aim of this study was to evaluate the protective effect of
      remote postischemic conditioning in patients undergoing elective PCI for stable
      angina or non-ST elevation acute coronary syndrome with troponin <1 ng/ml at the
      time of randomization. METHODS: This randomized single-blinded single-center
      clinical trial involved 320 patients undergoing elective PCI who were randomized
      to either receive three 5-min cycles of ischemia by inflation of a cuff on the
      non-dominant arm to 200 mm Hg (remote postischemic conditioning) or to placebo
      (uninflated cuff). The primary outcome variable was the maximum increase in
      troponin in the first 24 h. The secondary outcome variable was readmission due to
      heart failure or cardiovascular mortality after 1 year of follow-up. In addition,
      a diabetic population was studied. CONCLUSIONS: This clinical trial evaluated the
      possible reduction in intervention-related myocardial damage that was
      attributable to remote postischemic conditioning.

PMID- 21952350
TI  - [Molecular mechanism of bacterial sphingomyelinase C].

PMID- 21952351
TI  - [Analysis of regulatory system of toxin production by cell-cell signaling in
      Clostridium perfringens].

PMID- 21952352
TI  - [Genomic analyses of mechanisms of virulence evolution in enterohemorrhagic E.
      coli and enteropathogenic E. coli].

PMID- 21952353
TI  - Intracranial ultrasound abnormalities and fetal cytomegalovirus infection: report
      of 8 cases and review of the literature.
AB  - OBJECTIVES: The aim of this study was to evaluate fetal intracranial and other
      ultrasonographic findings in cytomegalovirus (CMV) infection. METHODS: Data on
      amniotic fluid CMV-DNA-PCR-positive pregnancies detected in our institution
      between January 2006 and June 2009 were reviewed retrospectively. Fetal biometric
      measurements, fetal anatomy, amniotic fluid volume, placental thickness and
      texture were analyzed for abnormalities. RESULTS: Eight fetuses were diagnosed
      with congenital CMV infection during the study interval. Their mean gestational
      age at diagnosis was 25.8 weeks (range: 23-29). All fetuses had intracranial
      abnormalities; increased periventricular echogenicity (n = 7), ventriculomegaly
      (n = 5), intracranial calcifications (n = 4), intraventricular adhesions (n = 4),
      thalamic hyperechogenicity (n = 3), mega cisterna magna (n = 3), lissencephaly (n
      = 2), vermian defect (n = 2) and cerebellar cyst (n = 1). All of them had
      accompanying extracranial findings, including hyperechogenic bowel (n = 6),
      cardiomegaly (n = 3), pericardial effusion (n = 2) and hepatosplenomegaly (n =
      1). Intrauterine growth retardation was detected in 3 cases. Five pregnancies
      were terminated, and 1 intrauterine death occurred. The remaining 2 delivered
      vaginally at term. One of the live-born babies suffers from tetraparesis, mental
      retardation and autism, and the other has mild hemiplegia. CONCLUSIONS: The
      spectrum of sonographic findings may vary widely in patients with congenital CMV
      infection in the prenatal period. CMV should be kept in mind in differential
      diagnosis, particularly in fetuses with intracranial sonographic findings such as
      ventriculomegaly, calcifications, intraventricular adhesions and increased
      periventricular echogenicity.

PMID- 21952354
TI  - Colorimetric detection of c-Kit mutations using electrostatic attraction induced
      aggregation of peptide nucleic acid modified gold nanoparticles.
AB  - We report a colorimetric detection of c-Kit mutations using selective aggregation
      of the peptide nucleic acid modified gold nanoparticles that is caused by
      electrostatic attraction.

PMID- 21952355
TI  - 18F-fluorodeoxyglucose and 131I radioguided surgical management of thyroid
      cancer.
AB  - OBJECTIVE: To describe a technique that assists in the surgical management of
      recurrent local regional well-differentiated thyroid cancer (WDTC). STUDY DESIGN:
      Case series with chart review. SETTING: Two academic health centers from 2001 to
      2009. SUBJECTS AND METHODS: Patients operated upon by the senior surgeon (BCS)
      for recurrent WDTC. RESULTS: Thirteen patients with recurrent WDTC were operated
      upon with radioguided surgical (RGS) technique to indentify recurrence for
      excision. Eight patients had iodine avid disease and were candidates for RGS with
      (131)I. The remaining 5 patients had cancer with a proven loss of iodine avidity
      and were, therefore, operated upon with a fluorodeoxygluocose (FDG) RGS
      technique. CONCLUSION: RGS is a feasible approach to identify recurrent disease
      in an operated field and ensure its successful excision. Although focal disease
      may be identified with this technique, this is not a tool for limited excisions
      ("berry picking").

PMID- 21952356
TI  - Silent sinus syndrome after lateral fracture of the inferior turbinate.

PMID- 21952357
TI  - Effect of silymarin in the treatment of allergic rhinitis.
AB  - OBJECTIVE: Although the role of oxidative stresses has been confirmed in the
      pathophysiology of allergic rhinitis and the protective effect of silymarin
      against oxidative stresses has been proven in different organs, no study has yet
      been conducted on the impact of silymarin on allergic rhinitis treatment. STUDY
      DESIGN: A randomized clinical trial study. SETTING: Two tertiary referral centers
      with otorhinolaryngology-head and neck surgery and allergy and immunology
      departments. PATIENTS AND METHODS: In a randomized clinical trial, 94 patients
      with the signs and symptoms of allergic rhinitis and a positive skin prick test
      were selected and randomly divided into 2 groups. Their signs and symptoms,
      eosinophil percentage on nasal smear, serum IgE, and interleukin (IL-4, IL-5,
      interferon-gamma) levels were recorded. The study group was treated with
      silymarin, whereas the control group received placebo, both for 1 month, along
      with routine antihistamine treatment. At the end of the treatment course,
      clinical and laboratory findings were statistically analyzed. RESULTS: Sixty
      patients completed the trial. Based on the Sino-Nasal Outcome Test 20 (SNOT-20),
      a significant improvement in clinical symptom severity was observed in both
      groups (9.23 +/- 5.14 vs 2.20 +/- 2.69; P < .001), which was statistically
      significantly higher in the study group (P < .001). Posttreatment percentage of
      nasal eosinophils and cytokine levels showed no significant difference (P > .05).
      Rise in serum IgE level was seen after treatment with silymarin (P = .003).
      CONCLUSION: Considering the statistically effective role of silymarin in
      alleviating the severity of allergic rhinitis symptoms, applying this herbal
      antioxidant along with other medications may result in better management.

PMID- 21952358
TI  - Current world literature.

PMID- 21952360
TI  - A density functional theory study of uranium(VI) nitrate monoamide complexes.
AB  - Density functional theory calculations were performed on uranyl complexed with
      nitrate and monoamide ligands (L) [UO(2)(NO(3))(2).2L]. The obtained results show
      that the complex stability is mainly governed by two factors: (i) the
      maximization of the polarizability of the coordinating ligand and (ii) the
      minimization of the steric hindrance effects. Furthermore, the electrostatic
      interaction between ligands and uranium(vi) was found to be a crucial parameter
      for the complex stability. These results pave the way to the definition of
      (quantitative) property/structure relationships for the in silico screening of
      monoamide ligands with improved extraction efficiency of uranium(vi) in nitrate
      acidic solution.

PMID- 21952361
TI  - Feasibility of using global positioning systems (GPS) with diverse urban adults:
      before and after data on perceived acceptability, barriers, and ease of use.
AB  - BACKGROUND: Global positioning systems (GPS) have emerged as a research tool to
      better understand environmental influences on physical activity. This study
      examined the feasibility of using GPS in terms of perceived acceptability,
      barriers, and ease of use in a racially/ethnically diverse sample of lower
      socioeconomic position (SEP). METHODS: Data were from 2 pilot studies involving a
      total of 170 African American, Hispanic, and White urban adults with a mean
      (standard deviation) age of 47.8 (+/-13.1) years. Participants wore a GPS for up
      to 7 days. They answered questions about GPS acceptability, barriers (wear
      related concerns), and ease of use before and after wearing the GPS. RESULTS: We
      found high ratings of GPS acceptability and ease of use and low levels of wear
      related concerns, which were maintained after data collection. While most were
      comfortable with their movements being tracked, older participants (P < .05) and
      African Americans (P < .05) reported lower comfort levels. Participants who were
      younger, with higher education, and low incomes were more likely to indicate that
      the GPS made the study more interesting (P < .05). Participants described
      technical and wear-related problems, but few concerns related to safety, loss, or
      appearance. CONCLUSIONS: Use of GPS was feasible in this racially/ethnically
      diverse, lower SEP sample.

PMID- 21952362
TI  - Commentary on 'Decompressive hemicraniectomy for pediatric traumatic brain
      injury: long-term outcome based on quality of life' by Arun T. Jacob et al.,
      Pediatr Neurosurg DOI: 10.1159/000329624.

PMID- 21952363
TI  - Cysteine and histidine shuffling: mixing and matching cysteine and histidine
      residues in zinc finger proteins to afford different folds and function.
AB  - Zinc finger proteins utilize zinc for structural purposes: zinc binds to a
      combination of cysteine and histidine ligands in a tetrahedral coordination
      geometry facilitating protein folding and function. While much is known about the
      classical zinc finger proteins, which utilize a Cys(2)His(2) ligand set to
      coordinate zinc and fold into an anti-parallel beta sheet/alpha helical fold,
      there are thirteen other families of 'non-classical' zinc finger proteins for
      which relationships between metal coordination and protein structure/function are
      less defined. This 'Perspective' article focuses on two classes of these non
      classical zinc finger proteins: Cys(3)His type zinc finger proteins and
      Cys(2)His(2)Cys type zinc finger proteins. These proteins bind zinc in a
      tetrahedral geometry, like the classical zinc finger proteins, yet they adopt
      completely different folds and target different oligonucleotides. Our current
      understanding of the relationships between ligand set, metal ion, fold and
      function for these non-classical zinc fingers is discussed.

PMID- 21952364
TI  - Culture-based and denaturing gradient gel electrophoresis analysis of the
      bacterial community structure from the intestinal tracts of earthworms(Eisenia
      fetida).
AB  - The bacterial communities in the intestinal tracts of earthworm were investigated
      by culture-dependent and - independent approaches. In total, 72 and 55 pure
      cultures were isolated from the intestinal tracts of earthworms under aerobic and
      anaerobic conditions, respectively. Aerobic bacteria were classified as Aeromonas
      (40%), Bacillus (37%), Photobacterium (10%), Pseudomonas (7%), and Shewanella
      (6%). Anaerobic bacteria were classified as Aeromonas (52%), Bacillus (27%),
      Shewanella (12%), Paenibacillus (5%), Clostridium (2%), and Cellulosimicrobium
      (2%). The dominant microorganisms were Aeromonas and Bacillus species under both
      aerobic and anaerobic conditions. In all, 39 DNA fragments were identified by
      polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE)
      analysis. Aeromonas sp. was the dominant microorganism in feeds, intestinal
      tracts, and casts of earthworms. The DGGE band intensity of Aeromonas from feeds,
      intestinal tracts, and casts of earthworms was 12.8%, 14.7%, and 15.1%,
      respectively. The other strains identified were Bacillus, Clostridium,
      Enterobacter, Photobacterium, Pseudomonas, Shewanella, Streptomyces, uncultured
      Chloroflexi bacterium, and uncultured bacterium. These results suggest that PCR
      DGGE analysis was more efficient than the culture-dependent approach for the
      investigation of bacterial diversity and the identification of unculturable
      microorganisms.

PMID- 21952365
TI  - Salinity stress resistance offered by endophytic fungal interaction between
      Penicillium minioluteum LHL09 and glycine max. L.
AB  - Endophytic fungi are little known for their role in gibberellins (GAs) synthesis
      and abiotic stress resistance in crop plants. We isolated 10 endophytes from the
      roots of field-grown soybean and screened their culture filtrates (CF) on the GAs
      biosynthesis mutant rice line - Waito-C. CF bioassay showed that endophyte GMH-1B
      significantly promoted the growth of Waito-C compared with controls. GMH-1B was
      identified as Penicillium minioluteum LHL09 on the basis of ITS regions rDNA
      sequence homology and phylogenetic analyses. GC/MS-SIM analysis of CF of P.
      minioluteum revealed the presence of bioactive GA(4) and GA(7). In endophyte
      soybean plant interaction, P. minioluteum association significantly promoted
      growth characteristics (shoot length, shoot fresh and dry biomasses, chlorophyll
      content, and leaf area) and nitrogen assimilation, with and without sodium
      chloride (NaCl)-induced salinity (70 and 140 mM) stress, as compared with
      control. Field-emission scanning electron microcopy showed active colonization of
      endophyte with host plants before and after stress treatments. In response to
      salinity stress, low endogenous abscisic acid and high salicylic acid
      accumulation in endophyte-associated plants elucidated the stress mitigation by
      P. minioluteum. The endophytic fungal symbiosis of P. minioluteum also increased
      the daidzein and genistein contents in the soybean as compared with control
      plants, under salt stress. Thus, P. minioluteum ameliorated the adverse effects
      of abiotic salinity stress and rescued soybean plant growth by influencing
      biosynthesis of the plant's hormones and flavonoids.

PMID- 21952366
TI  - Cell death mediated by Vibrio parahaemolyticus type III secretion system 1 is
      dependent on ERK1/2 MAPK, but independent of caspases.
AB  - Vibrio parahaemolyticus, which causes gastroenteritis, wound infection, and
      septicemia, has two sets of type III secretion systems (TTSS), TTSS1 and TTSS2. A
      TTSS1- deficient vcrD1 mutant of V. parahaemolyticus showed an attenuated
      cytotoxicity against HEp-2 cells, and a significant reduction in mouse lethality,
      which were both restored by complementation with the intact vcrD1 gene. V.
      parahaemolyticus also triggered phosphorylation of mitogenactivated protein
      kinases (MAPKs) including p38 and ERK1/2 in HEp-2 cells. The ability to activate
      p38 and ERK1/2 was significantly affected in a TTSS1-deficient vcrD1 mutant.
      Experiments using MAPK inhibitors showed that p38 and ERK1/2 MAPKs are involved
      in V. parahaemolyticus-induced death of HEp-2 cells. In addition, caspase-3 and
      caspase-9 were processed into active forms in V. parahaemolyticus-exposed HEp-2
      cells, but activation of caspases was not essential for V.
      parahaemolyticusinduced death of HEp-2 cells, as shown by both annexin V staining
      and lactate dehydrogenase release assays. We conclude that secreted protein(s) of
      TTSS1 play an important role in activation of p38 and ERK1/2 in HEp-2 cells that
      eventually leads to cell death via a caspaseindependent mechanism.

PMID- 21952368
TI  - Antidiabetic activities of extract from Malva verticillata seed via the
      activation of AMP-activated protein kinase.
AB  - Stimulation of AMP-activated protein kinase (AMPK) signaling followed by increase
      of glucose uptake in L6 myotubes were studied with organic solvent extract of
      Malva verticillata (MV) seeds. Ethanol extract of M. verticillata seeds (MVE)
      significantly increased the phosphorylation level of AMPK, acetyl-CoA carboxylase
      (ACC), and glucose uptake in L6 myotube cells. The MVE was fractionated with n
      hexane (MVE-H), chloroform (MVE-C), ethylacetate (MVE-E), n-butanol (MVE-B), and
      water (MVE-W). MVE-H (150 microgram/ml) showed the highest phosphorylating
      activity and increased glucose uptake by 2.3-fold. Oral administration of MVE-H
      (40 mg/kg) for 4 weeks to type 2 diabetic (db/db) mice reduced non-fasting and
      fasting blood glucose levels by 17.1% and 23.3%, respectively. Phosphorylation
      levels of AMPK and ACC in the soleus muscle and liver tissue of db/db mice were
      significantly increased by the administration of MVE-H. MVE-H was further
      fractionated using preparative HPLC to identify the AMPK-activating compounds.
      The NMR and GC-MS analyses revealed that beta-sitosterol was a major effective
      compound in MVE-H. Phosphorylation levels of AMPK and ACC, and glucose uptake
      were significantly increased by the treatment of MVE-S (beta-sitosterol) isolated
      from M. verticillata to L6 cells, and these effects were attenuated by an AMPK
      inhibitor (Compound C) pretreatment. These results, taken together, demonstrate
      that increased glucose uptake in L6 myotubes by MVE-H treatment is mainly
      accomplished through the activation of AMPK. Our finding suggests that the
      extract isolated from M. verticillata seed would be beneficial for the treatment
      of metabolic disease including type 2 diabetes and hyperlipidemia.

PMID- 21952367
TI  - Molecular cloning and characterization of mannitol-1-phosphate dehydrogenase from
      Vibrio cholerae.
AB  - Vibrio cholerae utilizes mannitol through an operon of the phosphoenolpyruvate
      dependent phosphotransferase (PTS) type. A gene, mtlD, encoding mannitol-1
      phosphate dehydrogenase was identified within the 3.9 kb mannitol operon of V.
      cholerae. The mtlD gene was cloned from V. cholerae O395, and the recombinant
      enzyme was functionally expressed in E. coli as a 6*His-tagged protein and
      purified to homogeneity. The recombinant protein is a monomer with a molecular
      mass of 42.35 kDa. The purified recombinant MtlD reduced fructose 6-phosphate
      (F6P) using NADH as a cofactor with a K(m) of 1.54 +/- 0.1 mM and V(max) of 320.8
      +/- 7.81 micronmol/min/mg protein. The pH and temperature optima for F6P
      reduction were determined to be 7.5 and 37 degrees C, respectively. Using
      quantitative real-time PCR analysis, mtlD was found to be constitutively
      expressed in V. cholerae, but the expression was up-regulated when grown in the
      presence of mannitol. The MtlD expression levels were not significantly different
      between V. cholerae O1 and non-O1 strains.

PMID- 21952369
TI  - Wewakamide A and guineamide G, cyclic depsipeptides from the marine cyanobacteria
      Lyngbya semiplena and Lyngbya majuscula.
AB  - Two new cyclic depsipeptides wewakamide A (1) and guineamide G (2) have been
      isolated from the marine cyanobacterium Lyngbya semiplena and Lyngbya majuscula,
      respectively, collected from Papua New Guinea. The amino and hydroxy acid partial
      structures of wewakamide A and guineamide G were elucidated through extensive
      spectroscopic techniques, including HR-FABMS, 1D (1)H and (13)C NMR, as well as
      2D COSY, HSQC, HSQCTOCSY, and HMBC spectra. The sequence of the residues of
      wewakamide A was determined through a combination of ESI-MS/MS, HMBC, and ROESY.
      Wewakamide A possesses a beta-amino acid, 3-amino-2-methylbutanoic acid (Maba)
      residue, which has only been previously identified in two natural products,
      guineamide B (3) and dolastatin D (4). Although both new compounds (1,2) showed
      potent brine shrimp toxicity, only guineamide G displayed significant
      cytotoxicity to a mouse neuroblastoma cell line with LC(50) values of 2.7
      micrometer.

PMID- 21952370
TI  - Molecular characterization of a novel vegetative insecticidal protein from
      Bacillus thuringiensis effective against sap-sucking insect pest.
AB  - Several isolates of Bacillus thuringiensis (Bt) were screened for the vegetative
      insecticidal protein (Vip) effective against sap-sucking insect pests. Screening
      results were based on LC(50) values against cotton aphid (Aphis gossypii), one of
      the dangerous pests of various crop plants including cotton. Among the isolates,
      the Bt#BREF24 showed promising results, and upon purification the aphidicidal
      protein was recognized as a binary toxin. One of the components of this binary
      toxin was identified by peptide sequencing to be a homolog of Vip2A that has been
      reported previously in other Bacillus spp. Vip2 belongs to the binary toxin group
      Vip1-Vip2, and is responsible for the enzymatic activity; and Vip1 is the
      translocation and receptor binding protein. The two genes encoding the
      corresponding proteins of the binary toxin, designated as vip2Ae and vip1Ae, were
      cloned from the Bt#BREF24, sequenced, and heterologously expressed in Escherichia
      coli. Aphid feeding assay with the recombinant proteins confirmed that these
      proteins are indeed the two components of the binary toxins, and the presence of
      both partners is essential for the activity. Aphid specificity of the binary
      toxin was further verified by ligand blotting experiment, which identified an ~50
      kDa receptor in the brush border membrane vesicles of the cotton aphids only, but
      not in the lepidopteran insects. Our finding holds a promise of its use in future
      as a candidate gene for developing transgenic crop plants tolerant against sap
      sucking insect pests.

PMID- 21952371
TI  - Parametric optimization of feruloyl esterase production from Aspergillus terreus
      strain GA2 isolated from tropical agro-ecosystems cultivating sweet sorghum.
AB  - A fungal strain, Aspergillus terreus strain GA2, isolated from an agricultural
      field cultivating sweet sorghum, produced feruloyl esterase using maize bran. In
      order to obtain maximum yields of feruloyl esterase, the solid state fermentation
      (SSF) conditions for enzyme production were standardized. Effective feruloyl
      esterase production was observed with maize bran as substrate followed by wheat
      bran, coconut husk, and rice husk among the tested agro-waste crop residues.
      Optimum particle size of 0.71- 0.3 mm and moisture content of 80% favored enzyme
      production. Moreover, optimum feruloyl esterase production was observed at pH 6.0
      and a temperature of 30 degrees C. Supplementation of potato starch (0.6%) as the
      carbon source and casein (1%) as the nitrogen source favored enzyme production.
      Furthermore, the culture produced the enzyme after 7 days of incubation when the
      C:N ratio was 5. Optimization of the SSF conditions revealed that maximum enzyme
      activity (1,162 U/gds) was observed after 7 days in a production medium of 80%
      moisture content and pH 6.0 containing 16 g maize bran [25% (w/v)] of particle
      size of 0.71-0.3 mm, 0.6% potato starch, 3.0% casein, and 64 ml of formulated
      basal salt solution. Overall, the enzyme production was enhanced by 3.2-fold as
      compared with un-optimized conditions.

PMID- 21952372
TI  - Profiling of recovery efficiencies for three standard protocols (FDA-BAM, ISO
      11290, and modified USDA) on temperature-injured Listeria monocytogenes.
AB  - There have been a number of studies conducted in order to compare the
      efficiencies of recovery rates, utilizing different protocols, for the isolation
      of L. monocytogenes. However, the severity of multiple cell injury has not been
      included in these studies. In the current study, L. monocytogenes ATCC 19112 was
      injured by exposure to extreme temperatures (60 degrees C and -20 degrees C) for
      a one-step injury, and for a two-step injury the cells were transferred directly
      from a heat treatment to frozen state to induce a severe cell injury (up to 100%
      injury). The injured cells were then subjected to the US Food and Drug
      Administration (FDA), the ISO-11290, and the modified United States Department of
      Agriculture (mUSDA) protocols, and plated on TSAyeast (0.6% yeast), PALCAM agar,
      and CHROMAgar Listeria for 24 h or 48 h. The evaluation of the total recovery of
      injured cells was also calculated based on the costs involved in the preparation
      of media for each protocol. Results indicate that the mUSDA method is best able
      to aid the recovery of heat-injured, freeze-injured, and heat-freeze-injured
      cells and was shown to be the most cost effective for heat-freeze-injured cells.

PMID- 21952373
TI  - Optimization of tannase production by Aspergillus niger in solid-state packed-bed
      bioreactor.
AB  - Tannin acyl hydrolase, also known as tannase, is an enzyme with important
      applications in the food, feed, pharmaceutical, and chemical industries. However,
      despite a growing interest in the catalytic properties of tannase, its practical
      use is very limited owing to high production costs. Several studies have already
      demonstrated the advantages of solid-state fermentation (SSF) for the production
      of fungal tannase, yet the optimal conditions for enzyme production strongly
      depend on the microbial strain utilized. Therefore, the aim of this study was to
      improve the tannase production by a locally isolated A. niger strain in an SSF
      system. The SSF was carried out in packed-bed bioreactors using polyurethane foam
      as an inert support impregnated with defined culture media. The process
      parameters influencing the enzyme production were identified using a Plackett
      Burman design, where the substrate concentration, initial pH, and incubation
      temperature were determined as the most significant. These parameters were then
      further optimized using a Box-Behnken design. The maximum tannase production was
      obtained with a high tannic acid concentration (50 g/l), relatively low
      incubation temperature (30 degrees C), and unique low initial pH (4.0). The
      statistical strategy aided in increasing the enzyme activity nearly 1.97-fold,
      from 4,030 to 7,955 U/l. Consequently, these findings can lead to the development
      of a fermentation system that is able to produce large amounts of tannase in
      economical, compact, and scalable reactors.

PMID- 21952374
TI  - Mannitol production by Leuconostoc citreum KACC 91348P isolated from Kimchi.
AB  - Leuconostoc genus, which comprise heterofermentative lactic acid bacteria,
      reduces fructose to mannitol by recycling intracellular NADH. To evaluate the
      mannitol productivities of different Leuconostoc species, 5 stock cultures and 4
      newly isolated strains were cultivated in MRS and simplified media containing
      glucose and fructose (1:2 ratio). Among them, L. citreum KACC 91348P, which was
      isolated from kimchi, showed superior result in cell growth rate, mannitol
      production rate, and yield in both media. The optimal condition for mannitol
      production of this strain was pH 6.5 and 30 degrees C. When L. citreum KACC was
      cultured in simplified medium in a 2 l batch fermenter under optimal conditions,
      the maximum volumetric productivity was 14.83 g.l(-1)h(-1) and overall yield was
      86.6%. This strain is a novel and efficient mannitol producer originated from
      foods to be used for fermentation of fructose-containing foods.

PMID- 21952375
TI  - Repeated-batch operation of immobilized beta-galactosidase inclusion bodies
      containing Escherichia coli cell reactor for lactose hydrolysis.
AB  - In this study, we investigated the performance of an immobilized beta
      galactosidase inclusion bodies-containing Escherichia coli cell reactor, where
      the cells were immobilized in alginate beads, which were then used in repeated
      batch operations for the hydrolysis of o-nitrophenyl-beta-D-galactoside or
      lactose over the long-term. In particular, in the Tris buffer system,
      disintegration of the alginate beads was not observed during the operation, which
      was observed for the phosphate buffer system. The o-nitrophenyl-beta-D
      galactoside hydrolysis was operated successfully up to about 80 h, and the runs
      were successfully repeated at least eight times. In addition, hydrolysis of
      lactose was successfully carried out up to 240 h. Using Western blotting
      analyses, it was verified that the beta-galactosidase inclusion bodies were
      sustained in the alginate beads during the repeated-batch operations.
      Consequently, we experimentally verified that beta-galactosidase inclusion bodies
      containing Escherichia coli cells could be used in a repeated-batch reactor as a
      biocatalyst for the hydrolysis of o-nitrophenyl-beta-D-galactoside or lactose. It
      is probable that this approach can be applied to enzymatic synthesis reactions
      for other biotechnology applications, particularly reactions that require long
      term and stable operation.

PMID- 21952376
TI  - Roles of putative sodium-hydrogen antiporter (SHA) genes in S. coelicolor A3(2)
      culture with pH variation.
AB  - Culture pH change has some important roles in signal transduction and secondary
      metabolism. We have already reported that acidic pH shock enhanced actinorhodin
      production in Streptomyces coelicolor. Among many potential governing factors on
      pH variation, the putative Na(+)/H(+) antiporter (sha) genes in S. coelicolor
      have been investigated in this study to elucidate the association of the sha on
      pH variation and secondary metabolism. Through the transcriptional analysis and
      overexpression experiments on 8 sha genes, we observed that most of the sha
      expressions were promoted by pH shock, and in the opposite way the pH changes and
      actinorhodin production were enhanced by the overexpression of each sha. We also
      confirmed that sha8 especially has a main role in maintaining cell viability and
      pH homeostasis through Na(+) extrusion, in salt effect experiment under the
      alkaline medium condition by deleting sha8. Moreover, this gene was observed to
      have a function of pH recovery after pH variation such as the pH shock, being
      able to cause the sporulation. However, actinorhodin production was not induced
      by the only pH recovery. The sha8 gene could confer on the host cell the ability
      to recover pH to the neutral level after pH variation like a pH drop. Sporulation
      was closely associated with this pH recovery caused by the action of sha8,
      whereas actinorhodin production was not due to such pH variation patterns alone.

PMID- 21952377
TI  - Effect of ammonium concentration on the emission of N(2)O under oxygen-limited
      autotrophic wastewater nitrification.
AB  - A significant amount of nitrous oxide (N(2)O), which is one of the serious
      greenhouse gases, is emitted from nitrification and denitrification of
      wastewater. Batch wastewater nitrifications with enriched nitrifiers were carried
      out under oxygen-limited condition with synthetic (without organic carbon) and
      real wastewater (with organic carbon) in order to find out the effect of ammonium
      concentration on N(2)O emission. Cumulated N(2)O-N emission reached 3.0, 5.7,
      6.2, and 13.5 mg from 0.4 l of the synthetic wastewater with 50, 100, 200, and
      500 mg/l NH(4)(+)-N, respectively, and 1.0 mg from the real wastewater with 125
      mg/l NH(4)(+)-N. The results indicate that N(2)O emission increased with ammonium
      concentration and the load. The ammonium removal rate and nitrite concentration
      also increased N(2)O emission. Comparative analysis of N(2)O emission from
      synthetic and real wastewaters revealed that wastewater nitrification under
      oxygen-limited condition emitted more N(2)O than that of heterotrophic
      denitrification. Summarizing the results, it can be concluded that
      denitrification by autotrophic nitrifiers contributes significantly to the N(2)O
      emission from wastewater nitrification.

PMID- 21952378
TI  - Bioremediation of crude oil by white rot fungi Polyporus sp. S133.
AB  - The bioremediation potential of crude oil by Polyporus sp. S133 pre-grown in wood
      meal was investigated in two separate experiment trials; liquid medium and soil.
      The effect of three nutrients (glucose, polypeptone, and wood meal), oxygen flow,
      and some absorbent on the efficiency of the process was also evaluated.
      Degradation of crude oil in soil was significantly increased with an addition of
      oxygen flow and some absorbent (kapok and pulp). The highest degradation rate of
      crude oil was 93% in the soil with an addition of 10% kapok. The present study
      clearly demonstrates that, if suitably developed, Polyporus sp. S133 could be
      used to remediate soil contaminated with crude oil.

PMID- 21952379
TI  - Vaccination to prevent otitis media in New Zealand.

PMID- 21952380
TI  - Stroke Services in New Zealand: should where you live determine the quality of
      stroke care you receive?

PMID- 21952381
TI  - New Zealand National Acute Stroke Services Audit 2009: organisation of acute
      stroke services in New Zealand.
AB  - AIMS: To characterise the nature of acute stroke services provided by District
      Health Boards (DHBs) in New Zealand. METHODS: An audit of all 21 DHBs was carried
      out in 2009 via an online survey examining the structural and process elements of
      acute stroke service provision. A clinical audit involving a retrospective review
      of consecutive admitted stroke patients is reported separately. RESULTS: The
      organisational survey found that most patients (82%) are admitted to hospitals in
      the 13 large and medium DHBs. Only 8 DHBs had stroke units and 5 of the large and
      medium DHBs did not have stroke units. On audit day, only 39% of all New Zealand
      patients were being managed in a stroke unit, compared with 51% of all Australian
      patients. Even in the 8 DHBs with stroke units, only 64% of patients were
      actually being managed in the stroke unit on the day of the audit. New Zealand
      compared favourably with Australia in aspects of TIA management and in access to
      brain imaging. CONCLUSION: There is significant regional variation in the
      provision of organised stroke care and the level of stroke unit care is low by
      international standards. This audit provides a benchmark against which to compare
      future changes in the delivery of stroke care.

PMID- 21952382
TI  - Quality-of-life outcomes for adult cochlear implant recipients in New Zealand.
AB  - AIM: There were two aims to this study: to investigate the effect of a cochlear
      implant (CI) on quality-of-life (QOL) for adult recipients in New Zealand; and to
      determine which aspects of life that these changes are most noticed. METHOD:
      There were two groups of participants: CI Group - 94 postlingually deafened adult
      CI recipients; and WL group - 70 postlingually deafened adults on the waiting
      list (WL) for a CI. Two questionnaires were developed for this study. RESULTS:
      The results showed that cochlear implantation had a significant positive impact
      on QOL for recipients. The CI group had significantly higher ratings in all areas
      of QOL and satisfaction compared to the WL group. CONCLUSION: Overall, high QOL
      and satisfaction ratings were obtained from CI recipients. The significantly
      lower ratings from those on the WL for an implant highlight the difficulties
      experienced by those with a significant hearing impairment. Assessment of CI
      outcomes should include QOL measures in order to provide a more holistic picture.

PMID- 21952383
TI  - Patterns of ophthalmic referral and emergency presentations to an acute tertiary
      eye service in New Zealand.
AB  - BACKGROUND: To establish demographics, referral patterns and clinical
      characteristics of patients attending an emergency eye service within a major
      public tertiary teaching hospital and to identify possible targets to improve
      delivery of patient care. METHODS: Retrospective study of all patients (N=504)
      attending an acute eye clinic over a representative 2-week period within
      Greenlane Clinical Centre, Auckland. RESULTS: Mean age was 42.4 plus or minus
      20.6 years with mean visual acuity of 6/10. Referrals came from: general
      practitioners (GP) (26.2%), self-referrals (18.6%), hospital medical-officers
      (7.4%), accident and emergency clinics (6.6%) and optometrists (2.2%). 39.1% of
      patients were follow-up reviews. Main presenting symptoms were pain, red eye and
      reduced vision. Average waiting-time was 119 plus or minus 98 min. Major
      diagnoses were trauma, uveitis and adenoviral keratoconjunctivitis (AKC). Males
      were more likely to present with ocular trauma, whereas females were more likely
      to exhibit uveitis, contact-lens related keratitis and AKC. Outcomes included
      follow-up (48.2%), referral to speciality ophthalmology care (19.0%), referral to
      other clinics (5.75%), and discharge (33.7%). CONCLUSION: A significant
      proportion of presentations could have been appropriately referred to outpatient
      departments or potentially managed by primary healthcare providers. Potential
      initiatives to manage excessive workload demands might target prevention of
      ocular trauma, improved contact-lens education, limiting the spread of AKC and
      improved GP education.

PMID- 21952384
TI  - Severe cyclophosphamide-induced haemorrhagic cystitis treated with hyperbaric
      oxygen.
AB  - AIM: Cyclophosphamide-induced haemorrhagic cystitis (CHC) is an uncommon but well
      recognised condition caused by a metabolite, acrolein, which is toxic to the
      urothelium. Based on similarities in the histopathology of radiation- and
      chemotherapy-induced haemorrhagic cystitis, benefit from hyperbaric oxygen
      therapy (HBOT) has been proposed. HBOT produces an increased oxygen partial
      pressure diffusion gradient between the circulation and surrounding tissues,
      which enhances neutrophil function and fibroblast and macrophage migration into
      damaged hypoxic soft tissue, promoting collagen formation, fibroblast growth,
      angiogenesis and white-cell bacterial killing. There are only isolated case
      reports of HBOT for CHC, in the literature so we reviewed the New Zealand
      experience with HBOT in CHC. METHOD: The case records of all patients with CHC
      referred to the three hyperbaric medicine units in New Zealand between 2000 and
      2007 were reviewed retrospectively. RESULTS: Six patients, with life-threatening
      haemorrhage at the time of referral for HBOT weeks or months after initial
      presentation with CHC, were identified. Cessation of bleeding occurred in all six
      patients after 14 to 40 HBOT, without complications. All patients remained clear
      of haematuria at 11 to 36 months follow-up. CONCLUSIONS: We recommend the use of
      HBOT in the management of intractable cyclophosphamide-induced haemorrhagic
      cystitis as an effective and low-risk therapy.

PMID- 21952385
TI  - Spinal manipulation: an update of a systematic review of systematic reviews.
AB  - OBJECTIVES: The aim of this update is to critically evaluate the evidence for or
      against the effectiveness of spinal manipulation in patients with any type of
      clinical condition. DESIGN: Four electronic databases were searched to identify
      all relevant systematic reviews of the effectiveness of spinal manipulation in
      any condition published between 2005 and January 2011. Reviews were defined as
      systematic, if they included an explicit and repeatable inclusion and exclusion
      criteria for studies. RESULTS: Forty-five systematic reviews were included
      relating to the following conditions: low back pain (n=7), headache (n=6), neck
      pain (n=4), asthma (n=4), musculoskeletal conditions (n=3), any non
      musculoskeletal conditions (n=2), fibromyalgia (n=2), infant colic (n=2), any
      medical problem (n=1), any paediatric conditions (n=1), carpal tunnel syndrome
      (n=1), cervicogenic dizziness (n=1), dysmenorrhoea (n=1), gastrointestinal
      problems (n=1), hypertension (n=1), idiopathic scoliosis (n=1), lateral
      epicondylitis (n=1), lower extremity conditions (n=1), pregnancy and related
      conditions (n=1), psychological outcome (n=1), shoulder pain (n=1), upper
      extremity conditions (n=1) and whiplash injury (n=1). Positive or, for multiple
      SR, unanimously positive conclusions were drawn for psychological outcomes (n=1)
      and whiplash (n=1). CONCLUSION: Collectively these data fail to demonstrate
      convincingly that spinal manipulation is an effective intervention for any
      condition.

PMID- 21952386
TI  - CPR in New Zealand hospitals: an alternate perspective on lawfulness and ways to
      improve practice.
AB  - The current approach to CPR in New Zealand hospitals is that it is attempted on
      all patients in cardiac arrest unless a DNR order is in place. Concern has been
      raised that this approach results in some "unlawful" CPR on the grounds that it
      is not in the patient's best interests. It has been suggested that policy change
      is required and one suggestion is a move away from DNR orders to mandatory "For
      CPR" orders. Ensuring lawfulness of CPR and more importantly quality care for
      patients is however more likely to be achieved not by policy change but by
      improved understanding by doctors and patients of the nature of these decisions,
      and by training programmes and work environments which value and facilitate
      difficult conversations, mutually respectful relationships and shared decisions.

PMID- 21952387
TI  - A large tricuspid valve mass associated with rectal carcinoma.

PMID- 21952388
TI  - A case of tricuspid valve endocarditis due to Burkholderia cepacia complex.
AB  - Burkholderia cepacia complex organisms are environmental Gram-negative bacteria
      which rarely cause disease in otherwise immunocompetent individuals. We describe
      a case of tricuspid valve endocarditis secondary to B. cepacia complex in an
      injecting intravenous drug user in Auckland, New Zealand.

PMID- 21952389
TI  - Medical image. Cutis marmorata.

PMID- 21952390
TI  - New Zealand's shocking diabetes rates can be reduced--9 urgently needed actions.

PMID- 21952391
TI  - The chiropractic profession: a response to Shaun Holt's letter.

PMID- 21952392
TI  - Chiropractor code of ethics: the importance of setting a good example.

PMID- 21952393
TI  - Improvement in the accuracy of hospital ethnicity data.

PMID- 21952394
TI  - The need for a uniform approach to paediatric pain management in emergency
      departments (EDs).

PMID- 21952395
TI  - A better night's sleep: an audit of medications used to treat insomnia in a
      psychiatric inpatient unit.

PMID- 21952397
TI  - Evaluation of different fluoride concentrations supplemented with
      trimetaphosphate on enamel de- and remineralization in vitro.
AB  - Trimetaphosphate (TMP) effects on demineralized bovine enamel were studied after
      15 days of pH cycling. Treatments included 30 wt% (weight percent) dilutions of
      0, 500, 1,500 or 3,000 MUg F/g aqueous NaF solutions with or without 3% TMP.
      Treated specimens were assessed by transverse microradiography. With the
      exception of the 3,000 MUg F/g case, 3% TMP addition provided significant
      additional overall remineralization compared with F alone. Mineral content
      profiles differed significantly between corresponding F and F + TMP groups.
      Fluoride alone resulted in more remineralization in the original demineralized
      zone, whereas F + TMP caused less demineralization in the underlying, originally
      sound enamel.

PMID- 21952398
TI  - Comparison of behavioral effects of morphine and fentanyl in dogs and cats.
AB  - Behavioral effects induced by intravenous administration of morphine at 0.3, 0.6,
      1.2, and 2.4 ug/kg and fentanyl at 5, 10, 20, and 40 ug/kg were evaluated in dogs
      and cats. In dogs, fentanyl and morphine depressed activity and level of
      consciousness in a dose- dependant manner. In cats, higher doses of fentanyl
      stimulated activity temporarily, but excitement, so-called "opioid mania," was
      not observed. Morphine induced distinctive behavioral changes characterized by
      sitting with fixed staring, and "opioid mania" was not observed in cats.

PMID- 21952399
TI  - Lectin binding pattern of gastric mucosa of pacific white-sided dolphin,
      Lagenorhynchus obliquidens.
AB  - The stomach of the Pacific white-sided dolphin is divided into three parts:
      forestomach, proper gastric gland portion, and pyloric chamber. The histological
      features of the dolphin stomach are similar to those of terrestrial mammal
      stomachs, although the distribution of glycoconjugates in mucosal cells of the
      dolphin stomach is unknown. To learn about glycoconjugates in cetacean gastric
      mucosa, the glycoconjugate distribution in the mucous epithelium of the Pacific
      white-sided dolphin was studied using 21 lectins. Among the lectins tested, GSL-I
      and DBA specifically labelled the superficial layer of the forestomach
      epithelium. GSL-I, SBA, RCA-I, VVA, GSL-II, DSL, LEL, STL, s-WGA, WGA, PNA, and
      Jacalin labelled the luminal surface of the chief cells in the proper gastric
      gland. GSL-I, SBA, RCA-I, DSL, LEL, STL, s-WGA, PNA, and LCA labelled tubular
      structures in the cytoplasm of parietal cells. The surface portion of the pits in
      the pyloric chamber strongly reacted with RCA-I, GSL-II, WGA, PNA, LCA, PHA-L,
      and UEA-I, whereas the neck portion reacted weakly. Although lining one tubular
      portion, individual secretory cells in the pyloric gland displayed a
      heterogeneous reaction. This is the first report on the lectin histochemistry of
      a cetacean stomach and reveals GSL-I and DBA as specific marker lectins for the
      cornified stratified squamous epithelium cells of the Pacific white-sided
      dolphin. The stomachs of cetaceans and terrestrial mammals have similar
      histological features and mucous glycoconjugate content.

PMID- 21952400
TI  - Identification and characterization of feline UBE1L gene.
AB  - Interferon-stimulated gene 15 (ISG15) is one of the type I interferon-inducible
      proteins. Addition of ISG15 known as ISGylation is an ubiquitin-like
      posttranslational modification. Coexpression of ISG15 and ubiquitin-activating
      enzyme E1-like protein (UBE1L) is required to induce ISGylation. Previously, we
      identified feline ISG15 gene and found that the capsid protein of feline
      immunodeficiency virus was ISGylated in vitro by treatment with feline interferon
      omega. In this study, we cloned feline UBE1L (FeUBE1L) gene to further study the
      mechanism of the antiviral activities induced by ISGylation. Sequencing analysis
      revealed that active sites of FeUBE1L were highly conserved. These data suggest
      that FeUBE1L has an enzymatic activity. Further, expression of FeUBE1L was
      induced in feline cell lines by treatment with feline interferon-omega and ovine
      interferon-tau.

PMID- 21952401
TI  - Polymorphic porous supramolecular networks mediated by halogen bonds on Ag(111).
AB  - Intermolecular structures of porous two-dimensional supramolecular networks are
      studied using scanning tunnelling microscopy combined with density functional
      theory calculations. The local configurations of halogen bonds in polymorphic
      porous supramolecular networks are directly visualized in support of previous
      bulk crystal studies.

PMID- 21952405
TI  - Effect of level of presentation to listeners on scaled speech intelligibility of
      speakers with dysarthria.
AB  - OBJECTIVE: This study examined the effect of intensity level of presentation on
      scaling of speech intelligibility in speakers with and without dysarthria.
      PATIENTS AND METHODS: A total of 50 utterances produced by speakers with
      dysarthria and healthy speakers were played to 60 listeners in four conditions,
      which consisted of two different presentation levels ('high' vs. 'low') and
      equalization of levels across utterances ('adjusted' vs. 'unadjusted'). Speech
      intelligibility was scaled by using a direct magnitude estimation technique with
      and without modulus. RESULTS: A significant decrease in speech intelligibility
      was indicated when the stimuli were adjusted to have fixed intensity on the most
      intense vocalic nuclei of each word, while no significant change was found
      between 'high' and 'low' presentation level conditions. CONCLUSION: The findings
      suggest that an increase in presentation level alone does not result in
      significant improvement in speech intelligibility ratings. The results are
      discussed by considering clinical implications in conducting speech therapy with
      emphasis on intensity variation.

PMID- 21952406
TI  - Current world literature.

PMID- 21952408
TI  - Early detection of non-ST-elevation myocardial infarction in geriatric patients
      by a new high-sensitive cardiac troponin T assay.
AB  - BACKGROUND AND AIMS: The new high sensitivity cardiac Troponin T (cTnThs) assay
      has recently been introduced in our clinic and ensures higher sensitivity than
      the fourth-generation cardiac troponin T (cTnT) assay from the same manufacturer
      (Roche Diagnostics). We determined the diagnostic performance of the cTnThs
      compared with the cTnT assay in geriatric patients, especially those with non-ST
      elevation myocardial infarction (NSTE- MI). METHODS: We retrospectively analysed
      253 patients (age 82 +/- 8 years; 82 men, 172 women) with diagnoses of suspected
      NSTEMI admitted to our Department of Geriatric Medicine. Patients were divided
      into one group of 113 patients using cTnThs, and another of 140 patients using
      cTnT for diagnosis. Each group included patients at the same months but different
      years, in either cTnThs or cTnT assays. NSTEMI was diagnosed according to current
      guidelines. RESULTS: Baseline characteristics were similar in both groups. The
      proportions of patients with elevated cardiac troponin (cTn) levels significantly
      increased from 35% in the cTnT group to 76% in the cTnThs group (p<0.001),
      although no coronary cause for the elevated cTn levels was shown in about two
      thirds of these patients. In patients with NSTE- MI, 58% in the cTnThs group vs
      42% in the cTnT group were diagnosed within 4 hours of the onset of symptoms,
      whereas 42% in the cTnThs group vs 58% in the cTnT group were diagnosed more than
      4 hours later (p=0.018). CONCLUSIONS: The prevalence of elevated cTn has more
      than doubled with the use of cTnThs. However, no coronary cause was found in two
      thirds of our geriatric patients, al- though more NSTEMI patients were diagnosed
      earlier by cTnThs.

PMID- 21952409
TI  - Reshaping of vertebrae during treatment with neridronate or pamidronate in
      children with osteogenesis imperfecta.
AB  - BACKGROUND/AIMS: Osteogenesis imperfecta (OI) is a hereditary disease causing
      increased bone fragility. Pamidronate (PAM), which has to be administered as a 3
      day course according to the original protocol by Glorieux, is the most frequently
      used therapy. Other bisphosphonates like neridronate (NER), which can be infused
      during an outpatient visit, have also proven to be effective. This is the first
      analysis comparing the effect of PAM and NER using vertebral morphometry.
      METHODS: 28 patients with OI type III and IV were retrospectively analyzed by
      matched pairs. RESULTS: No differences were detected between patients treated
      with PAM or NER at the start of therapy: mean age 4.4 years (p = 0.730), mean
      height 86.8 cm/85.3 cm (p = 0.854), lumbar vertebral area 208.9 mm(2)/206.0 mm(2)
      (p = 0.555), and in all vertebral indices. After 1 year of treatment (mean 1.16
      years; p = 0.854) both groups showed a significant increase in the vertebral area
      and improved vertebral indices. Again there were no differences between the
      groups in the vertebral area (p = 0.590). CONCLUSION: In this study there was no
      difference between patients treated with PAM or NER regarding vertebral
      morphometry during the first year of therapy. Because of the possibility of an
      outpatient setting, NER is convenient for these children.

PMID- 21952410
TI  - Polyelectrolyte nanocages via crystallized miniemulsion droplets.
AB  - Polyelectrolyte nanocages were synthesized by interfacial cross-linking of
      monolayers of vinyl-functionalized surfactant molecules adsorbed by crystallized
      miniemulsion droplets. The monolayer-thick shell of these nanocages was confirmed
      by AFM analysis.

PMID- 21952411
TI  - Phosphidation of Li4Ti5O12 nanoparticles and their electrochemical and
      biocompatible superiority for lithium rechargeable batteries.
AB  - Phosphidated-Li(4)Ti(5)O(12) shows high capacity with a significantly enhanced
      kinetics opening new possibilities for ultra-fast charge/discharge of lithium
      rechargeable batteries. The in vitro cytotoxicity test proves its fabulous cell
      viability, indicating that the toxicity problem of nanoparticles can be also
      solved by phosphidation.

PMID- 21952412
TI  - Bronsted acid-catalyzed enantioselective Friedlander condensations: achiral amine
      promoter plays crucial role in the stereocontrol.
AB  - A highly enantioselective Friedlander condensation has been established by using
      chiral Bronsted acids in combination with achiral amines to give quinolines in
      high yields (up to 99%) and with excellent enantioselectivities (up to 95%).

PMID- 21952413
TI  - Evaluation of a questionnaire to assess sedentary and active behaviors in the
      Southern Community Cohort Study.
AB  - BACKGROUND: Low physical activity (PA) is linked to cancer and other diseases
      prevalent in racial/ethnic minorities and low-income populations. This study
      evaluated the PA questionnaire (PAQ) used in the Southern Cohort Community Study,
      a prospective investigation of health disparities between African-American and
      white adults. METHODS: The PAQ was administered upon entry into the cohort (PAQ1)
      and after 12-15 months (PAQ2) in 118 participants (40-60 year-old, 48% male, 74%
      African-American). Test-retest reliability (PAQ1 versus PAQ2) was assessed using
      Spearman correlations and the Wilcoxon signed rank test. Criterion validity of
      the PAQ was assessed via comparison with a PA monitor and a last-month PA survey
      (LMPAS), administered up to 4 times in the study period. RESULTS: The PAQ test
      retest reliability ranged from 0.25-0.54 for sedentary behaviors and 0.22-0.47
      for active behaviors. The criterion validity for the PAQ compared with PA monitor
      ranged from 0.21-0.24 for sedentary behaviors and from 0.17-0.31 for active
      behaviors. There was general consistency in the magnitude of correlations between
      the PAQ and PA-monitor between African-Americans and whites. CONCLUSIONS: The
      SCCS-PAQ has fair to moderate test-retest reliability and demonstrated some
      evidence of criterion validity for ranking participants by their level of
      sedentary and active behaviors.

PMID- 21952415
TI  - Size control and quantum confinement in Cu2ZnSnS4 nanocrystals.
AB  - Starting with metal dithiocarbamate complexes, we synthesize colloidal
      Cu(2)ZnSnS(4) (CZTS) nanocrystals with diameters ranging from 2 to 7 nm.
      Structural and Raman scattering data confirm that CZTS is obtained rather than
      other possible material phases. The optical absorption spectra of nanocrystals
      with diameters less than 3 nm show a shift to higher energy due to quantum
      confinement.

PMID- 21952414
TI  - Carbohydrate hydration: heavy water complexes of alpha and beta anomers of
      glucose, galactose, fucose and xylose.
AB  - The singly and doubly hydrated complexes of the alpha and beta anomers of a
      systematically varied set of monosaccharides, O-phenyl D-gluco-, D-galacto-, L
      fuco- and D-xylopyranoside, have been generated in a cold molecular beam and
      probed through infrared-ultraviolet double resonance ion-dip (IRID) spectroscopy
      coupled with quantum mechanical calculations. A new 'twist' has been introduced
      by isotopic substitution, replacing H(2)O by D(2)O to separate the carbohydrate
      (OH) and hydrate (OD) vibrational signatures and also to relieve spectral
      congestion. The new spectroscopic and computational results have exposed subtle
      aspects of the intermolecular interactions which influence the finer details of
      their preferred structures, including the competing controls exerted by co
      operative hydrogen bonding, bi-furcated and OH-pi hydrogen bonding,
      stereoelectronic changes associated with the anomeric effect, and dispersion
      interactions. They also reassert the operation of general 'working rules'
      governing conformational change and regioselectivity in both singly and doubly
      hydrated monosaccharides.

PMID- 21952416
TI  - A robust pure hydrocarbon derivative based on the (2,1-b)-indenofluorenyl core
      with high triplet energy level.
AB  - A unique (2,1-b)-indenofluorenyl core flanked with two spirofluorene units,
      possessing a high triplet energy value and excellent thermal/morphological
      stability, is reported.

PMID- 21952417
TI  - High levels of comorbidity and disability cancel out the dementia effect in
      predictions of long-term mortality after discharge in the very old.
AB  - BACKGROUND/AIMS: The relative weight of various etiologies of dementia as
      predictors of long-term mortality after other risk factors have been taken into
      account remains unclear. We investigated the 5-year mortality risk associated
      with dementia in elderly people after discharge from acute care, taking into
      account comorbid conditions and functionality. METHODS: A prospective cohort
      study of 444 patients (mean age: 85 years; 74% female) discharged from the acute
      geriatric unit of Geneva University Hospitals. On admission, each subject
      underwent a standardized diagnostic evaluation: demographic variables, cognitive,
      comorbid medical conditions and functional assessment. Patients were followed
      yearly by the same team. Predictors of survival at 5 years were evaluated by Cox
      proportional hazards models. RESULTS: The univariate model showed that being
      older and male, and having vascular and severe dementia, comorbidity and
      functional disability, were predictive of shorter survival. However, in the full
      multivariate model adjusted for age and sex, the effect of dementia type or
      severity completely disappeared when all the variables were added. In
      multivariate analysis, the best predictor was higher comorbidity score, followed
      by functional status (R(2) = 23%). CONCLUSIONS: The identification of comorbidity
      and functional impairment effects as predictive factors for long-term mortality
      independent of cognitive status may increase the accuracy of long-term discharge
      planning.

PMID- 21952418
TI  - A comparison of the Endurance Shuttle Walk test and the Six Minute Walk test for
      assessment of exercise capacity in older people.
AB  - BACKGROUND AND AIMS: The six minute walk test is widely used to measure aerobic
      exercise capacity in older people, but lack responsiveness to change. We aimed to
      compare the reliability, responsiveness and completion rates of the six minute
      walk with a new test of aerobic exercise capacity - the endurance shuttle walk
      test. METHODS: Two groups were studied: 18 patients from a Medicine for the
      Elderly Day Hospital (study 1) receiving physiotherapy, and 15 community dwelling
      older people (study 2) receiving caffeine or placebo in a crossover study,
      followed by a weekly exercise programme. Six minute walk test and endurance
      shuttle walk test were performed at baseline and after interventions. Intraclass
      correlation coefficients were calculated for reliability, and Cohen's effect
      sizes were calculated to characterize responsiveness. RESULTS: 6/18 of patients
      in study 1 completed the baseline shuttle walk successfully. For those completing
      baseline and week one shuttle walk, similar intraclass correlation coefficients
      were seen (shuttle walk 0.97; six minute walk 0.90). In study 2, all attendees
      completed baseline and follow-up shuttle walk. 7/15 managed the maximum shuttle
      walk time at baseline. Effect sizes for caffeine intervention (0.29 for six
      minute walk, 0.01 for shuttle walk) and for exercise intervention (0.15 for six
      minute walk, 0.24 for shuttle walk) were similarly low for both tests.
      CONCLUSION: The endurance shuttle walk is no more responsive to change than the
      six minute walk in older people, is limited by ceiling effects, and cannot be
      performed successfully by very frail older people.

PMID- 21952419
TI  - New distributional records and conservation implications for the critically
      endangered greater bamboo lemur Prolemur simus.
AB  - To improve our knowledge of the distribution of the critically endangered greater
      bamboo lemur Prolemur simus, we surveyed 6 sites in eastern Madagascar. We found
      its characteristic feeding signs at 5 sites and made a direct sighting at one of
      these. One site represents a northern extension of 45 km of the known extant
      range of the species. Two sites are located in a forest corridor approximately
      halfway between the previously known southern and northern populations, therefore
      suggesting a broadly continuous distribution of the species within its range
      rather than the previously suspected distribution of two distinct populations
      separated by a distance of over 200 km. Our results illustrate the benefit of
      species-focussed surveys in determining the true distribution of endangered
      species, a realistic measure which is necessary in order to assess their current
      status and to prioritise long-term conservation interventions.

PMID- 21952420
TI  - Relationship between recurrent miscarriage and insulin resistance.
AB  - AIMS: To investigate the differences in insulin resistance between women with
      recurrent miscarriage and those with normal pregnancy. METHODS: Pregnant women
      with a history of recurrent miscarriage were included in the patient group (n =
      97), while those with no history of abnormal pregnancy were included in the
      control group (n = 52). Both groups consented to undertake an oral glucose
      tolerance test and insulin-releasing test between the 5th and 13th weeks of
      pregnancy. RESULTS: (1) Levels of fasting plasma glucose, fasting plasma insulin,
      homeostasis model assessment of insulin resistance index, and homeostasis model
      assessment beta function were not statistically significantly different (p <
      0.05) between the two groups. (2) The area under the curve of glucose and area
      under the curve of insulin were higher in the patient group than in the control
      group. The composite insulin sensitivity index of the patient group was lower
      than that of the control group. The differences in these three parameters between
      the groups were statistically significant (p < 0.05). CONCLUSION: Women with a
      history of recurrent miscarriage are at an increased risk for insulin resistance
      during the first trimester of a new pregnancy.

PMID- 21952421
TI  - Road traffic noise: self-reported noise annoyance versus GIS modelled road
      traffic noise exposure.
AB  - BACKGROUND AND OBJECTIVES: self-reported road traffic noise annoyance is commonly
      used in epidemiological studies for assessment of potential health effects.
      Alternatively, some studies have used geographic information system (GIS)
      modelled exposure to road traffic noise as an objective parameter. The aim of
      this study was to analyse the association between noise exposure due to
      neighbouring road traffic and the noise annoyance of adults, taking other
      determinants into consideration. METHODS: parents of 951 Munich children from the
      two German birth cohorts GINIplus and LISAplus reported their annoyance due to
      road traffic noise at home. GIS modelled road traffic noise exposure (L(den),
      maximum within a 50 m buffer) from the noise map of the city of Munich was
      available for all families. GIS-based calculated distance to the closest major
      road (>=10,000 vehicles per day) and questionnaire based-information about family
      income, parental education and the type of the street of residence were explored
      for their potential influence. An ordered logit regression model was applied. The
      noise levels (L(den)) and the reported noise annoyance were compared with an
      established exposure-response function. RESULTS: the correlation between noise
      annoyance and noise exposure (L(den)) was fair (Spearman correlation r(s) =
      0.37). The distance to a major road and the type of street were strong predictors
      for the noise annoyance. The annoyance modelled by the established exposure
      response function and that estimated by the ordered logit model were moderately
      associated (Pearson's correlation r(p) = 0.50). CONCLUSIONS: road traffic noise
      annoyance was associated with GIS modelled neighbouring road traffic noise
      exposure (L(den)). The distance to a major road and the type of street were
      additional explanatory factors of the noise annoyance appraisal.

PMID- 21952422
TI  - One step continuous hydrothermal synthesis of very fine stabilized
      superparamagnetic nanoparticles of magnetite.
AB  - Stable suspensions of citrated SPIO nanoparticles were synthesised in one step
      using a hydrothermal continuous process. Citrates control the crystallite size
      and the oxidation degree of metallic ions despite the very short reaction time (4
      s). Magnetite particles, Fe(2.94)O(4), with an average size of 4 nm and good
      monodispersity were obtained.

PMID- 21952423
TI  - Association of HLA alleles with autoimmune thyroid disease in Korean children.
AB  - BACKGROUNDS: Data regarding genetics of Hashimoto's disease (HD) and Graves'
      disease (GD) in Korean children are lacking. METHODS: 73 patients with autoimmune
      thyroid disease (AITD; HD 32, GD 41) were recruited. We analyzed human leukocyte
      antigen (HLA) class I and HLA-DRB1 by PCR-SSP, and compared them with those of
      159 controls. RESULTS: In AITD, the allele frequencies of HLA-A*02, -B*46, -Cw*01
      and -DRB1*08 were higher and those of HLA-A*30, -B*07, -Cw*07 and -DRB1*01 were
      lower than in controls. In HD, those of HLA-B*46 and -Cw*01 were higher and those
      of HLA-DRB1*01 and -Cw*07 were lower than in controls. In GD, those of HLA-A*02, 
      B*46, -Cw*01 and -DRB1*08 were higher and those of HLA-DRB1*07 and -Cw*07 were
      lower than in controls. Between HD and GD, there were no significant differences
      in allele frequencies. The risk of AITD in the presence of both HLA-B*46 and 
      Cw*01 is higher than in the presence of either allele alone. CONCLUSION: The
      susceptible and protectable alleles in HD are similar to those in GD. Coexistence
      of HLA-B*46 and -Cw*01 may be a genetic gene marker for early-onset AITD in
      Koreans.

PMID- 21952427
TI  - Personal privacy, public benefits, and biobanks: A conjoint analysis of policy
      priorities and public perceptions.
AB  - PURPOSE:: To assess the public's perception of biobank research and the relative
      importance they place on concerns for privacy and confidentiality, when compared
      with other key variables when considering participation in biobank research.
      METHODS:: Conjoint analysis of three key attributes (research focus, research
      beneficiary, and privacy and confidentiality) under conditions of either blanket
      or specific consent. RESULTS:: Although the majority of our participants
      described themselves as private individuals, they consistently ranked privacy and
      confidentiality as the least important of the variables they considered. The
      potential beneficiary of proposed research ranked the highest under conditions of
      both blanket and specific consent. When completing the conjoint task under
      conditions of blanket consent, participants tended to act more altruistically.
      CONCLUSION:: The public tend to view biobanks as public goods designed primarily
      for public benefit. As such they tend to act altruistically with respect to the
      potential benefits that might accrue from research using biobanked samples.
      Participants expressed little concern about informational risks (i.e., privacy
      and confidentiality) should they choose to participate. The manner in which
      policy priorities are framed could impact participant value preferences with
      regard to a number of governance issues in biobanking.

PMID- 21952432
TI  - Pro-oxidative effect of peroxynitrite regarding biological systems: a special
      focus on high-molar-mass hyaluronan degradation.
AB  - Current understanding on the role of peroxynitrite in etiology and pathogenesis
      of some human diseases, such as cardio-vascular diseases, stroke, cancer,
      inflammation, neurodegenerative disorders, diabetes mellitus and diabetic
      complications has recently led to intensive investigation of peroxynitrite
      involvement in physiology and pathophysiology. Mechanism of cytotoxic effects of
      peroxynitrite involve its reactions with lipids, DNA/RNA, proteins, and
      polysaccharides, thus triggering cellular responses ranging from subtle changes
      of cell functioning to severe oxidative damage of the affected macromolecules
      leading to necrosis or apoptosis. The present work is aimed at providing a brief
      overview of i) peroxynitrite biosynthesis and reaction pathways in vivo, ii) its
      synthetic preparation in vitro, and iii) to reveal its potential damaging role in
      vivo, on actions studied via monitoring in vitro hyaluronan degradation. The
      complex biochemical behavior of peroxynitrite is determined by a number of
      variables, such as chemistry of the reaction itself, depending mostly on the
      involvement of conformational structures of different energy states,
      concentration of the species involved, content of reactive intermediates and
      trace transition metal ions, contribution of carbon dioxide, presence of trace
      organics, and by the reaction kinetics. Recently, in vitro studies of oxidative
      cleavage of hyaluronan have, in fact, been the subject of growing interest. Here
      we also describe our experimental set-up for studying peroxynitrite-mediated
      degradation of hyaluronan, a system, which may be suitable for testing
      prospective pharmacological substances.

PMID- 21952433
TI  - Investigation of ABC transporter from mycobacterial arabinogalactan biosynthetic
      cluster.
AB  - Two genes from the "mycobacterial arabinogalactan biosynthetic cluster" spanning
      the region from Rv3779 to Rv3809c in the genome of Mycobacterium tuberculosis
      H37Rv were annotated as possible components of the ATP-binding cassette
      transporter. Rv3781 encodes a nucleotide-binding domain and Rv3783 determines
      production of a membrane-spanning domain. We have examined possible roles of
      these genes in mycobacterial cell wall biosynthesis through inactivation of their
      respective orthologs in Mycobacterium smegmatis mc(2)155, phenotypic
      characterization of the mutant strains via metabolic labeling with [U-(14)C]
      glucose, cell-free reactions with UDP-[U-(14)C]-galactose monitoring galactan
      build-up and transcriptional analysis. Several lines of evidence suggest that
      this ABC transporter is involved in biosynthesis of arabinogalactan, although
      more investigation is needed to establish its precise role or the transported
      substrate.

PMID- 21952434
TI  - The beta isoenzyme of Ca(2+)/calmodulin-dependent kinase type II as possible
      mediator of somatostatin functions in pituitary tumour cells.
AB  - Somatostatin or somatostatin release inhibiting factor (SRIF) analogues are
      indicated for the treatment of somatotropinomas that hypersecrete growth hormone
      (GH). Indeed, SRIF inhibits intracellular Ca(2+) concentration ([Ca(2+)](i)),
      thus allowing the inhibition of GH secretion. In the present study, our
      hypothesis was that Ca(2+)/calmodulin-dependent kinase type II (CaMKII), a
      multifunctional serine/threonine protein kinase, is part of those signalling
      mechanisms mediating SRIF functions. All four CaMKII isoenzymes (termed alpha,
      beta, gamma and delta) are expressed in rat somatotroph GC cells, although only
      CaMKIIbeta is inhibited by SRIF at both mRNA and protein levels. Similarly to
      SRIF, the specific knockdown of CaMKIIbeta by RNA interference induces a decrease
      of [Ca(2+)](i). The effects of SRIF and those of CaMKIIbeta knockdown are non
      additive. These results are confirmed by the pharmacological blockade of CAMKII.
      We also observed that, similarly to SRIF, the specific knockdown of CaMKIIbeta
      induces a decrease of both GH content/secretion. These results raise the
      hypothesis that CaMKIIbeta may mediate, at least in part, the SRIF-induced
      control of [Ca(2+)](i). In addition, CaMKIIbeta seems to play a positive role in
      maintaining the exocytosis of GH. Our data provide a framework for better
      elucidating the pathophysiological role of SRIF transduction network in
      somatotropinomas.

PMID- 21952435
TI  - Modulations of behavioral consequences of minor cortical ischemic lesion by
      application of free radicals scavengers.
AB  - Functional and morphological consequences of ischemic lesions are partially
      related to the production of reactive oxygen species (ROS). The aim of the study
      was to create a unilateral photothrombic lesion with minimal morphological
      changes and minor sensorimotor and cognitive deficits and also to test whether
      the application of ROS scavengers after the end of induction of ischemia had
      improved the functional outcome. Adult Wistar male rats were randomly divided
      into five groups: naive control, sham operated animals, animals with induced
      ischemia, and two groups of animals with induced ischemia and subsequent ROS
      scavenger application -melatonin or tempol. The group subjected to ischemia
      showed a significant decline in performance in sensorimotor tests and the Morris
      water maze (MWM) test, compared to control animals. Tempol (50 mg/kg, i.p.) did
      not improve sensorimotor function and did not change spatial learning. Melatonin
      (100 mg/kg, i.p.), on the contrary, resulted in a significant improvement in
      animals' performances. All the ischemia subjected animals had increased speed of
      swimming in the MWM test, compared to the control group. Our findings showed that
      subsequent application of ROS scavengers improve ischemia outcomes, with
      melatonin being more potent. Conversely, neither melatonin, nor tempol decreased
      swimming speed cased by ischemia.

PMID- 21952436
TI  - Interaction between sympathetic nervous system and renin angiotensin system on
      MMPs expression in juvenile rat aorta.
AB  - The aim of our present study is to investigate the interaction between
      angiotensin II (ANG II) and sympathetic nervous system (SNS) on matrix
      metalloproteinase MMP-2 and MMP-9 expression and activity in juvenile rat aorta
      under normal conditions. Sympathectomy with guanethidine and blockade of the ANG
      II receptors (AT1R) by losartan were performed alone or in combination on new
      born rats. mRNA, protein expression and activity of MMP-2 and MMP-9 were examined
      by Q-RT-PCR, immunoblotting and zymography, respectively. MMP-2 mRNA and protein
      amount were decreased after sympathectomy or AT1R blockade and an additive effect
      was observed after combined treatment. However, MMP-9 expression was reduced to
      the same level in the three treated groups. There were some detectable
      gelatinolytic activity of the MMPs in both control and treated rats. We concluded
      that ANG II stimulates directly and indirectly (via sympathostimulator pathway)
      the MMP-2 expression but seems unable to affect MMP-9 expression through direct
      pathway. Combined inhibition of SNS and ANG II were more efficient than a single
      inhibition in reducing MMP amounts in rat vessels.

PMID- 21952437
TI  - Antidiabetic and antioxidant potentials of Euphorbia hirta leaves extract studied
      in streptozotocin-induced experimental diabetes in rats.
AB  - Euphorbia hirta, commonly known as asthma weed, is a popular folk remedy for the
      treatment of various ailments. Recent studies have indicated that plant has
      potent antioxidant properties. As part of an ongoing programme to validate the
      use of some reputed herbs in Indian traditional medicines, the present study was
      aimed to evaluate the antidiabetic and antioxidant potentials of E. hirta leaves
      in streptozotocin-induced experimental diabetes in rats. Oral administration of
      E. hirta leaves extract (300 mg/kg b.w./rat/day) for a period of 30 days
      indicated the antidiabetic nature of the leaves extract. Determination of the
      lipid peroxides, hydroperoxides, and both enzymatic and non-enzymatic
      antioxidants evidenced the antioxidant potential of the leaves extract. Assay of
      enzymes such as serum aspartate transaminase (AST), serum alanine transaminase
      (ALT) and serum alkaline phosphatase (ALP) revealed the non-toxic nature of E.
      hirta leaves. The hypoglycemic activity of the leaves extract was comparable with
      gliclazide, a standard reference drug.

PMID- 21952438
TI  - Study of membrane attachment and in vivo co-localization of TerB protein from
      uropathogenic Escherichia coli KL53.
AB  - The tellurite resistance operon has been found in a wide range of bacteria. We
      have previously identified the ter operon (terXYW and terZABCDEF) of the
      uropathogenic strain Escherichia coli KL53. In this study, we use an innovative
      approach to identify putative protein-protein interaction partners for one of the
      essential tellurite resistance proteins - TerB. We observe that N-terminus of
      TerB attaches to the periplasmic membrane, while the C-terminus is partly
      localized in the cytoplasm. Subsequently, by methods of in vivo cross-linking and
      mass-spectroscopic analysis, we have determined the proteins from both the
      membrane and cytoplasmic fractions, which can potentially interact with TerB.

PMID- 21952439
TI  - The effects of vitamin C and nitric oxide synthase inhibition on coronary flow
      and oxidative stress markers in isolated rat heart.
AB  - The aim of this study was to assess the effects of vitamin C (ascorbic acid) on
      coronary flow and oxidative stress markers with or without non-specific
      inhibition of nitric oxide synthase by N(omega)-nitro-L-arginine monomethyl ester
      (L-NAME) in isolated rat hearts. The hearts of male Wistar albino rats (n = 12,
      age 8 weeks, body mass 180-200 g) were retrograde perfused according to the
      Langendorff technique at gradually increased constant perfusion pressure (40-120
      cm H2O). Coronary flow, nitrite outflow, superoxide anion production, and index
      of lipid peroxidation (by measuring thiobarbituric acid reactive substances) in
      coronary effluent were determined. The experiments were performed during control
      conditions and in presence of vitamin C (100 uM) alone or vitamin C (100 uM) + L
      NAME (30 uM). Administration of vitamin C induced only increase of nitrite
      levels, while vitamin C + L-NAME induced significant decrease of coronary flow
      above autoregulatory range, i.e. especially at higher coronary perfusion pressure
      (CPP) values, accompanied with similar dynamic in nitrite outflow. Vitamin C + L
      NAME also induced significant decrease in TBARS production. The results of our
      study show no significant effects of vitamin C administration either on ROS
      levels or on coronary flow in isolated rat heart.

PMID- 21952440
TI  - Biophoton emissions from cell cultures: biochemical evidence for the plasma
      membrane as the primary source.
AB  - Photon emissions were measured at ambient temperature (21 degrees C) in complete
      darkness once per min from cultures of 10(6) cells during the 12 h following
      removal from 37 degrees C. The energy of emission was about 10(-20) J/s/cell. Of
      8 different cell lines, B16-BL6 (mouse melanoma cells) demonstrated the most
      conspicuous emission profile. Acridine orange and ethidium bromide indicated the
      membranes were intact with no indication of (trypan blue) cell necrosis.
      Treatments with EGF and ionomycin produced rapid early (first 3 h) increases in
      energy emission while glutamine-free, sodium azide and wortmanin-treated cells
      showed a general diminishment 3 to 9 h later. The results suggested the most
      probable origin of the photon emission was the plasma cell membrane. Measures
      from cells synchronized at the M- and S-phase supported this inference.

PMID- 21952441
TI  - Functional changes in the septal GABAergic system of animals with a model of
      temporal lobe epilepsy.
AB  - The septal GABAergic system plays a central role in the regulation of activity
      and excitability of the hippocampus (the main locus of temporal lobe epilepsy,
      TLE), but the character of changes the septum undergoes in this pathology remains
      unknown. To address this issue we studied the influences on GABAergic receptors
      in septal slices from the brain of epileptic guinea pigs compared to a control.
      In the epileptic brain, the overall increase in the mean frequency of neuronal
      discharges and the rise in the number of bursting neurons were revealed. The
      inhibitory action of exogenously applied GABA on neuronal activity is sharply
      enhanced, whereas the efficacy of action of GABA(A) and GABA(B) receptor blockers
      decreases, indicating the alteration of intraseptal inhibitory processes in
      epilepsy. In epilepsy, GABA sharply increases the oscillatory activity of the
      part of pacemakers, and the opposite effect was observed in the control. In
      epileptic animals, the GABA receptor blockers did not affect burst neurons,
      indicating the disturbance of the tonic GABAergic control of the oscillatory
      activity. Thus, we demonstrated for the first time that the activity of septal
      neurons and their reactions to GABAergic substances in animals with TLE model
      changed sharply compared to healthy ones.

PMID- 21952442
TI  - The effect of chronic food restriction on immunopositive ACTH cells in
      peripubertal female rats.
AB  - In peripubertal female rats, we have previously found that 50% food restriction
      (FR) increases plasma IL-6, haptoglobin and both alanine transaminase (ALT) and
      alkaline phosphatase (AST) aminotransferases, indicating the existence of an
      inflammatory response. To study whether such FR influences the hypothalamic
      pituitary-adrenal (HPA) axis, we examined by immunohistochemistry the
      morphofunctional features of pituitary adrenocorticotroppic (ACTH) cells. In FR
      rats the volume and volume density of ACTH cells as well as plasma ACTH levels
      were increased by 17.6%, 12.5% and 13.4%, respectively, in comparison with
      controls (p<0.05). We concluded that chronic FR is a systemic stressor in young
      females, capable to stimulate the HPA axis, probably as a result of IL-6 action.

PMID- 21952443
TI  - Growth of an oligopyridine adlayer on Ag(100)--a scanning tunnelling microscopy
      study.
AB  - The growth behaviour of the oligopyridine derivative 2-phenyl-4,6-bis(6-(pyridine
      2-yl)-4-(pyridine-4-yl)pyridine-2-yl)pyrimidine (2,4'-BTP) on Ag(100) in the sub
      monolayer regime was investigated by variable temperature scanning tunneling
      microscopy under ultra-high vacuum conditions. Over the entire coverage range,
      the molecules are adsorbed in a flat lying configuration, with preferential
      orientations with respect to the <110> direction of the surface. The azimuth
      angles are derived using a previously introduced algorithm that fits the
      positions of the intramolecular N atoms geometrically to the underlying surface
      lattice ("points-to-lattice fit") [H.E. Hoster et al., Langmuir 2007, 23, 11570],
      indicating that the orientation of the admolecules and thus of the adllayer
      structure with respect to the Ag(100) surface lattice is determined by the 2,4'
      BTP-Ag(100) interaction, while intermolecular interactions are decisive for the
      structure of the adlayer. The results will be compared to other adsorption
      systems.

PMID- 21952444
TI  - p-tert-Butylcalix[8]arene: a support for sodium and sodium-manganese clusters
      that exhibit interesting self-assembly properties.
AB  - A series of new sodium and mixed sodium/manganese clusters have been formed using
      p-tert-butylcalix[8]arene as a support. In all cases the calixarene adopts the
      pleated-loop conformation, and the resulting complexes show interesting self
      assembly properties depending on the ligated solvent molecules around individual
      cluster cores.

PMID- 21952445
TI  - Implementation of an electronic health record.

PMID- 21952446
TI  - UK drinking guidelines are better for the alcohol industry than the public.

PMID- 21952447
TI  - Predicting adult height from a child's current height.

PMID- 21952448
TI  - Voluntary approaches work in removal of artificial trans fats.

PMID- 21952449
TI  - Preventing NCDs through nutritional change is not as complex as it may seem.

PMID- 21952450
TI  - The sodium phantom.

PMID- 21952452
TI  - Full, not selective, information needed for melanoma risk.

PMID- 21952453
TI  - Arrow plots show results of meta-analyses of surrogate and clinical outcomes.

PMID- 21952454
TI  - The truth, such as it is, about melanoma risk.

PMID- 21952455
TI  - Use of Freedom of Information Act to produce research on the cheap?

PMID- 21952457
TI  - No comparative drug efficacy without legislation.

PMID- 21952458
TI  - Closing hospitals with warm sympathy.

PMID- 21952459
TI  - Drug approvals and size of prescribing pool.

PMID- 21952460
TI  - If and butts about smoking cessation.

PMID- 21952461
TI  - Health experts give qualified approval to previous government's health reforms.

PMID- 21952462
TI  - Imports of polio to China and western Africa threaten global eradication.

PMID- 21952463
TI  - US Supreme Court may have to settle dispute over patenting DNA sequences.

PMID- 21952464
TI  - First NHS club drug clinic opens its doors.

PMID- 21952465
TI  - Investigation into data fraud results in heart researcher's dismissal.

PMID- 21952466
TI  - Iron-catalyzed oxidative coupling of arylboronic acids with benzene derivatives
      through homolytic aromatic substitution.
AB  - Fe(OTf)(3)-1,10-phenanthroline catalyzes oxidative coupling of arylboronic acids
      with benzene derivatives using t-BuOOt-Bu as an oxidant. The reaction proceeds
      through homolytic aromatic substitution with aryl radicals generated from
      arylboronic acids and t-BuO.

PMID- 21952467
TI  - Immune profile and Epstein-Barr virus infection in acute interstitial nephritis:
      an immunohistochemical study in 78 patients.
AB  - BACKGROUND: Acute interstitial nephritis (AIN) is a common cause of acute kidney
      injury and is characterised by a dense interstitial cellular infiltrate, which
      has not been well defined. Previous studies have demonstrated a correlation
      between Epstein-Barr virus (EBV) infection and AIN. The purpose of our study was
      to define the nature of the interstitial immune infiltrate and to investigate the
      possibility of renal infection with EBV. METHODS: Seventy-eight patients with AIN
      were identified from renal biopsy reports in a single centre over an 18-year
      period. Immunohistochemical staining was performed to define the cellular
      infiltrate. In situ hybridization and immunohistology were used to detect EBV.
      RESULTS: A positive correlation between CD68 macrophage infiltration and serum
      creatinine concentration at presentation was identified. IL-4, eotaxin, CCR3,
      CCR5 and VCAM-1 were all expressed in biopsies of AIN. Using in situ
      hybridization and immunohistochemistry, EBV was not detected in any of the AIN
      sections analysed. CONCLUSION: This study has assessed the nature of the
      interstitial infiltrate in AIN. EBV was not detected in the renal biopsies,
      suggesting that EBV is not a pathogenetic factor in AIN.

PMID- 21952468
TI  - Phenotypic variability in fetuses with down syndrome: a case-control pathological
      evaluation.
AB  - OBJECTIVES: Evaluation of morphological and morphometric characteristics of
      fetuses with Down syndrome based on a detailed postmortem examination and
      comparison of these fetuses with a control group of fetuses with normal karyotype
      to improve the prenatal knowledge of Down syndrome characteristics. MATERIAL AND
      METHODS: A case-control study was undertaken in a tertiary referral hospital. The
      Down syndrome fetuses (50) were compared with chromosomally normal fetuses (47)
      matched for gestational age. Biometric and morphological parameters were
      compared. RESULTS: The biometry of fetuses with Down syndrome differs from
      control fetuses only in the occipitofrontal diameter and in the nasal bone
      length. There were craniofacial anomalies in 96% of fetuses with Down syndrome
      and in 51% of fetuses with normal karyotype. With the exception of small ears,
      all craniofacial features analyzed were significantly different between Down
      syndrome fetuses and control fetuses. All extremity features of fetuses with Down
      syndrome were significantly different from fetuses without Down syndrome. There
      were 31 fetuses with Down syndrome (62%) with 55 internal anomalies. Nineteen
      fetuses (38.8%) showed 27 cardiac anomalies. Six fetuses had more than one
      anomaly. There were 18 fetuses (36%) with 28 noncardiac anomalies. DISCUSSION:
      The importance of studying the morphological characteristics of fetuses with Down
      syndrome is the contribution to a better knowledge of fetal characteristics and
      probably to optimize prenatal diagnosis.

PMID- 21952469
TI  - Long-range atmospheric transport of persistent organochlorinated compounds from
      south and mainland south-eastern Asia to a remote mountain site in south-western
      China.
AB  - A range of organochlorinated compounds have been consumed in China, India and the
      countries of mainland southeast Asia (MSA). Considering their persistence in the
      environment and ability in long-range atmospheric transport (LRAT), the potential
      outflow of these compounds from this region is therefore of great concern in the
      context of the global distribution of toxic chemicals. As part of a monitoring
      campaign aimed at investigating the LRAT of organochlorine pesticides (OCPs) and
      polychlorinated biphenyls (PCBs) from southern China, MSA and northern India,
      atmospheric levels of OCPs and PCBs were measured once a week from October 2005
      through December 2006 at Tengchong Mountain (TM), a remote site located in south
      western China. The average concentrations of OCPs were found to be higher than
      those in other remote stations in the Arctic and the Tibetan plateau, except for
      alpha-hexachlorocyclohexane (alpha-HCH). A high level of beta-HCH and low alpha
      HCH/beta-HCH ratio was attributed to an accidental release of beta-HCH from
      unknown sources, besides obvious evidence of lindane (gamma-HCH) and technical
      HCH usage. Temporal variations of chlordanes and endosulfan were related to the
      usage pattern of these compounds, as well as LRAT. In contrast,
      dichlorodiphenyltrichloroethane (DDT) exhibited a relatively minor seasonal
      variation. The OCP levels at the monitoring site were found to be related to the
      air parcel back trajectories on the basis of four distinct clusters. Elevated
      levels of HCHs and DDTs were observed when air parcels originated from northern
      India where considerable OCP usage was reported recently, while high levels of
      gamma-HCH and TC (trans-chlordane) were mainly associated with air masses from
      southern China and northern MSA. The study highlighted the high background level
      of OCPs as well as their temporal patterns of trans-boundary LRAT in the MSA
      region.

PMID- 21952470
TI  - Staging dementia using proxy-reported activities of daily living.
AB  - BACKGROUND/AIM: It has been questioned whether cognitive and behavioral scales
      sufficiently address the impact of dementia on the everyday life of patients.
      Therefore, other instruments are used, such as scales of activities of daily
      living (ADL). Our goal was to analyze variables influencing the appraisal of ADL.
      METHOD: Prospective cohort study on 202 patients with dementia and their proxies.
      RESULTS: Two clusters of patients were identified. These clusters differed
      significantly in their constituting variables and all variables that informants
      reported regarding the patients. However, severity of dementia and other
      variables were similar in the two clusters. CONCLUSION: We conclude that ratings
      of basic and instrumental ADL by proxy are modulated by the informants'
      variables, particularly if these informants are female. Use of ADL scales to
      assess the impact of dementia or treatment thereof needs to be handled
      cautiously.

PMID- 21952475
TI  - Isolation of a cancer-associated microchromosome in the sperm-dependent
      parthenogen Poecilia formosa.
AB  - In the asexual all-female fish species Poecilia formosa, the Amazon molly,
      supernumerary chromosomes have frequently been found in both laboratory-reared
      and wild-caught individuals. While wild-caught individuals with B chromosomes are
      phenotypically indifferent from conspecifics, individuals carrying B chromosomes
      from recent introgression events in the laboratory show phenotypic changes.
      Former analyses showed that the expression of a pigment cell locus is associated
      with the presence of these B chromosomes. In addition, they contain a so far
      unidentified locus that confers a higher susceptibility to tumor formation in the
      presence of pigmentation pattern. Isolation by microdissection and hybridization
      to metaphase chromosomes revealed that they contain one or several sequences with
      similarity to a highly repetitive pericentromeric and subtelomeric sequence in A
      chromosomes. Isolation of one particular sequence by AFLP showed that the B
      chromosomes contain at least 1 copy of an A-chromosomal region which is highly
      conserved in the whole genus Poecilia, i.e. more than 5 million years old. We
      propose it to be a single copy sequence.

PMID- 21952476
TI  - Wilkinson's iridium acetate trimer as a water-oxidation catalyst.
AB  - The catalytic water-oxidation activity of Wilkinson's iridium acetate trimer (1)
      has been characterized electrochemically and by using chemical oxidants. We show
      that 1 can function as an operationally homogeneous water-oxidation catalyst when
      driven with sodium periodate as a primary oxidant, but rapidly decomposes using
      Ce(IV) as a primary oxidant.

PMID- 21952477
TI  - Monitoring mRNA in living cells in a 3D in vitro model using TAT-peptide linked
      molecular beacons.
AB  - There is a growing need for the development of in vitro 3D cell culture models
      for assessing newer therapeutics for clinical applications and mechanisms of
      human pathology. Molecular beacons have been successfully delivered in two
      dimensional (2D) systems to monitor, detect, and localize specific mRNA
      expression in living cells at the single cell level. However, to date the use of
      molecular beacons in three-dimensional (3D) systems has not been reported. To
      translate this technology into specific clinical targeted applications, it is
      critical to develop and demonstrate efficacy in a 3D system. For the first time
      the use of TAT-peptide conjugated molecular beacons to monitor mRNA in a 3D in
      vitro system has been reported.

PMID- 21952478
TI  - Designs for life: protocell models in the laboratory.
AB  - Compartmentalization of primitive biochemical reactions within membrane-bound
      water micro-droplets is considered an essential step in the origin of life. In
      the absence of complex biochemical machinery, the hypothetical precursors to the
      first biological cells (protocells) would be dependent on the self-organization
      of their components and physicochemical conditions of the environment to attain a
      basic level of autonomy and evolutionary viability. Many researchers consider the
      self-organization of lipid and fatty acid molecules into bilayer vesicles as a
      simple form of membrane-based compartmentalization that can be developed for the
      experimental design and construction of plausible protocell models. In this
      tutorial review, we highlight some of the recent advances and issues concerning
      the construction of simple cell-like systems in the laboratory. Overcoming many
      of the current scientific challenges should lead to new types of chemical bio
      reactors and artificial cell-like entities, and bring new insights concerning the
      possible pathways responsible for the origin of life.

PMID- 21952479
TI  - Open-shell spherical aromaticity: the 2N2 + 2N + 1 (with S = N + 1/2) rule.
AB  - 4N Baird's rule represented the extension of Huckel's 4N + 2 rule to triplet
      state systems. In this work we extend the 2(N + 1)(2) Hirsch rule for spherical
      aromatic species to open-shell spherical compounds and we provide evidence that
      those spherical species having a same-spin half-filled last energy level with the
      rest of the levels being fully-filled, i.e., those having 2N(2) + 2N + 1
      electrons and S = N + 1/2, are aromatic.

PMID- 21952480
TI  - Basic science for the clinician 53: mast cells.
AB  - Mast cells stand at the interface between the innate immune system and the
      acquired (adaptive) immune response, serving as sentinels detecting invaders and
      directing a concerted and coordinated response. Mast cells reside immediately
      under body surfaces and within lymph nodes, near blood vessels and nerves,
      perfectly situated to for early detection and defense. They secrete a wide array
      of prostanoids, cytokines, chemokines, and other proteins mediators and modifiers
      of a variety of immune and inflammatory functions and bear surface markers
      suggesting broad functions, including as antigen-presenting cells. Although
      usually not given their due in medical school lectures, there is great likelihood
      that mast cells will be implicated in the pathogenesis of rheumatoid arthritis,
      scleroderma, multiple sclerosis, and perhaps cancer. Thus, better insights into
      mast cell functions and mast cell-derived effector molecules should command our
      attention as we move forward in better understanding disease immunopathogenesis
      and directed intelligent therapeutics development.

PMID- 21952481
TI  - Antecubital fossa cyst in longstanding seropositive rheumatoid arthritis.

PMID- 21952482
TI  - Nail-patella syndrome.

PMID- 21952483
TI  - Pelvic finger: an unusual cause of pelvic pain.

PMID- 21952485
TI  - Familial osteopoikilosis.

PMID- 21952487
TI  - Modelling the evaporation of thin films of colloidal suspensions using dynamical
      density functional theory.
AB  - Recent experiments have shown that various structures may be formed during the
      evaporative dewetting of thin films of colloidal suspensions. Nanoparticle
      deposits of strongly branched 'flower-like', labyrinthine and network structures
      are observed. They are caused by the different transport processes and the rich
      phase behaviour of the system. We develop a model for the system, based on a
      dynamical density functional theory, which reproduces these structures. The model
      is employed to determine the influences of the solvent evaporation and of the
      diffusion of the colloidal particles and of the liquid over the surface. Finally,
      we investigate the conditions needed for 'liquid-particle' phase separation to
      occur and discuss its effect on the self-organized nanostructures.

PMID- 21952488
TI  - A turn-on fluorescence sensor for cyanide from mechanochemical reactions between
      quantum dots and copper complexes.
AB  - Manual grinding of CuCl(2), 2,2'-bipyridine and hydrophobic CdSe QDs creates a
      selective and fast turn-on fluorescence sensor for detection of nanogram
      quantities of solid cyanide salts by the naked-eye. Using a fluorescence detector
      this simple sensor detects 100 ppm of NaCN in sand.

PMID- 21952489
TI  - SymGF: a symbolic tool for quantum transport analysis and its application to a
      double quantum dot system.
AB  - We report the development and an application of a symbolic tool, called SymGF,
      for analytical derivations of quantum transport properties using the Keldysh
      nonequilibrium Green's function (NEGF) formalism. The inputs to SymGF are the
      device Hamiltonian in the second quantized form, the commutation relation of the
      operators and the truncation rules of the correlators. The outputs of SymGF are
      the desired NEGF that appear in the transport formula, in terms of the
      unperturbed Green's function of the device scattering region and its coupling to
      the device electrodes. For complicated transport analysis involving strong
      interactions and correlations, SymGF provides significant assistance in
      analytical derivations. Using this tool, we investigate coherent quantum
      transport in a double quantum dot system where strong on-site interaction exists
      in the side-coupled quantum dot. Results obtained by the higher-order
      approximation and Hartree-Fock approximation are compared. The higher-order
      approximation reveals Kondo resonance features in the density of states and
      conductances. Results are compared both qualitatively and quantitatively to the
      experimental data reported in the literature.

PMID- 21952491
TI  - Role of arginase in impairing relaxation of lung parenchyma of hyperoxia-exposed
      neonatal rats.
AB  - BACKGROUND: Prolonged exposure of immature lungs to hyperoxia contributes to
      neonatal lung injury and airway hyperreactivity. We have previously demonstrated
      that neonatal exposure of rat pups to >=95% O2 impairs airway relaxation due to
      disruption of nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signaling.
      OBJECTIVE: We now hypothesize that these impaired relaxation responses are
      secondary to hyperoxia-induced upregulation of arginase, which competes with NO
      synthase for L-arginine. METHODS: Rat pups were exposed to moderate neonatal
      hyperoxia (50% O2) or room air for 7 days from birth. In additional hyperoxic and
      room air groups, exogenous L-arginine (300 mg/kg/day i.p.) or arginase inhibitor
      (Nomega-hydroxy-nor-arginine, 30 mg/kg/day i.p.) were administered daily. After 7
      days, animals were anesthetized and sacrificed either for preparation of lung
      parenchymal strips or lung perfusion. RESULTS: In response to electrical field
      stimulation (EFS), bethanechol-preconstricted lung parenchymal strips from
      hyperoxic pups exhibited significantly reduced relaxation compared to room air
      controls. Supplementation of L-arginine or arginase blockade restored hyperoxia
      induced impairment of relaxation. Expression of arginase I in airway epithelium
      was increased in response to hyperoxia but reduced by arginase blockade. Arginase
      activity was also significantly increased in hyperoxic lungs as compared to room
      air controls and reduced following arginase blockade. EFS-induced production of
      NO was decreased in hyperoxia-exposed airway smooth muscle and restored by
      arginase blockade. CONCLUSION: These data suggest that NO-cGMP signaling is
      disrupted in neonatal rat pups exposed to even moderate hyperoxia due to
      increased arginase activity and consequent decreased bioavailability of the
      substrate L-arginine. We speculate that supplementation of arginine and/or
      inhibition of arginase may be a useful therapeutic tool to prevent or treat
      neonatal lung injury.

PMID- 21952492
TI  - Facile synthesis of superparamagnetic Fe3O4@Au nanoparticles for photothermal
      destruction of cancer cells.
AB  - Superparamagnetic Fe(3)O(4) nanoparticles with positive surface xi-potential were
      synthesized via a solvothermal route. After Fe(3)O(4) was mixed with HAuCl(4) and
      NaBH(4), the reduced Au nanoparticles could be directly adsorbed onto the surface
      of Fe(3)O(4) nanoparticles. The as-synthesized nanocomposites were successfully
      applied to photothermal destruction of cancer cells.

PMID- 21952493
TI  - Novel counter electrode catalysts of niobium oxides supersede Pt for dye
      sensitized solar cells.
AB  - Synthesized niobium oxides (Nb(2)O(5) and NbO(2)) were applied for the first time
      as counter electrodes (CEs) in dye-sensitized solar cells (DSCs). The DSC using
      NbO(2) CE showed a higher power conversion efficiency of 7.88%, compared with
      that of the DSC using Pt CE (7.65%).

PMID- 21952494
TI  - Carbonic anhydrase inhibitors: X-ray crystallographic studies for the binding of
      N-substituted benzenesulfonamides to human isoform II.
AB  - N-substituted benzenesulfonamides, incorporating the N-amino-, N-hydroxy- and N
      methoxy-moieties at the sulfonamide zinc binding group, have been investigated as
      CAIs by means of inhibition and structural studies, unraveling interesting
      aspects related to their inhibition mechanism.

PMID- 21952496
TI  - DNA-templated preparation of gold nanoparticles.
AB  - DNA-mediated gold nanoparticles were prepared by chemical reduction of DNA
      Au(III) complex. The DNA-Au(III) was first formed by reacting DNA with HAuCl4 at
      a pH of 5.6. The complex in solution was reacted with hydrazine reducing Au(III)
      to Au. The reduced Au formed nanodimensional aggregates. The particle
      distributions were obtained by scanning electron microscopy (SEM) and
      transmission electron microscopy (TEM). This method resulted in a rather uniform
      dispersion of Au nanoparticles of near-spherical shape and 45~80 nm in diameter.
      Gold nanoparticles were embedded and stabilized by DNA.

PMID- 21952495
TI  - Total versus hemithyroidectomy for microscopic papillary thyroid cancer.
AB  - BACKGROUND: No increased mortality has been reported in patients with thyroid
      papillary microcarcinoma (PMC); however, neck recurrences and distant metastases
      have been described. In this study, we compare patients' outcomes after total
      thyroidectomy vs hemithyroidectomy for treatment of thyroid PMC. METHODS: Two
      hundred and ninety-three patients from two major medical centers in Israel were
      included. The mean follow-up period was 7.2+/-6.8 yr. RESULTS: Total
      thyroidectomy was performed in 214 patients and hemithyroidectomy in 79 patients.
      Mean tumor size was 6.3+/-3 mm. Lymph-node (LN) metastases and extraglandular
      extension were more frequent in the total thyroidectomy group than in the
      hemithyroidectomy group, 24.8% vs 1.3% (p<0.001) and 11.7% vs 3.8% (p=0.042),
      respectively. The cumulative incidence of recurrence at the end of follow-up was
      13.2% in the total thyroidectomy group and 14.3% in the hemithyroidectomy group
      (p=ns). The incidence of recurrence was higher in patients with LN involvement in
      both groups. Considering low risk patients only (monofocal tumors, no LN
      involvement, no extraglandular extension; no.=63 in the total thyroidectomy group
      vs no.=60 in the hemithyroidectomy group) neck recurrence was found in 10% of
      patients in the hemithyroidectomy group but none in the total thyroidectomy
      group. In the hemithyroidectomy group, all locoregional recurrences were
      diagnosed using ultrasonography, compared to 47.6% in the total thyroidectomy
      group. CONCLUSION: For patients with monofocal disease within the thyroid gland
      and no LN involvement, hemithyroidectomy can be considered an option, bearing in
      mind a higher risk for recurrence. For all other patients with PMC, we propose
      total thyroidectomy as initial treatment.

PMID- 21952497
TI  - Chamaejasmine inactivates Akt to trigger apoptosis in human HEp-2 larynx
      carcinoma cells.
AB  - In the present study, we investigated the mechanisms of chamaejasmine action on
      human HEp-2 larynx carcinoma cells, which possess constitutively active Akt.
      Results indicated that chamaejasmine showed more notable anticancer activity than
      apigenin against HEp-2, PC-3, NCI-H1975, HT-29 and SKOV-3. Moreover,
      chamaejasmine presented most significantly inhibition towards HEp-2, with IC50
      values of 1.92 uM. Treatment of HEp-2 cells with chamaejasmine (1-4 MUM) resulted
      in significant dose-dependent decrease in Akt phosphorylation at Serine473.
      Chamaejasmine-mediated dephosphorylation of Akt resulted in inhibition of its
      kinase activity, which was confirmed by reduced phosphorylation of proapoptotic
      proteins BAD and glycogen synthase kinase-3, essential downstream targets of Akt.
      Inactivation of Akt seems to be associated with downregulation of insulin-like
      growth factor receptor 1 protein level and inhibition of its autophosphorylation
      upon chamaejasmine treatment. Exposure to chamaejasmine significantly induced
      caspase-9 and caspase-3 activity. In vivo, chamaejasmine intake through gavage
      resulted in inactivation of Akt and induction of apoptosis in HEp-2 tumors. These
      results suggest that Akt inactivation and dephosphorylation of BAD is a critical
      event, at least in part, in chamaejasmine-induced HEp-2 cells apoptosis.

PMID- 21952498
TI  - Chamaejasmine induces apoptosis in human lung adenocarcinoma A549 cells through a
      Ros-mediated mitochondrial pathway.
AB  - In the present study, the anticancer activity of chamaejasmine towards A549 human
      lung adenocarcinoma cells was investigated. In order to explore the underlying
      mechanism of cell growth inhibition of chamaejasmine, cell cycle distribution,
      ROS generation, mitochondrial membrane potential (Deltapsi(m)) disruption, and
      expression of cytochrome c, Bax, Bcl-2, caspase-3, caspase-9 and PARP were
      measured in A549 cells. Chamaejasmine inhibited the growth of A549 cells in a
      time and dose-dependent manner. The IC50 value was 7.72 uM after 72 h treatment.
      Chamaejasmine arrested the cell cycle in the G2/M phase and induced apoptosis via
      a ROS-mediated mitochondria-dependent pathway. Western blot analysis showed that
      chamaejasmine inhibited Bcl-2 expression and induced Bax expression to
      desintegrate the outer mitochondrial membrane and causing cytochrome c release.
      Mitochondrial cytochrome c release was associated with the activation of caspase
      9 and caspase-3 cascade, and active-caspase-3 was involved in PARP cleavage. All
      of these signal transduction pathways are involved in initiating apoptosis. To
      the best of our knowledge, this is the first report demonstrating the cytotoxic
      activity of chamaejasmine towards A549 in vitro.

PMID- 21952499
TI  - Comparison of clinical outcomes between 'on-flap' and 'off-flap' epi-LASIK for
      myopia: a meta-analysis.
AB  - OBJECTIVE: To examine possible differences in clinical outcomes between off-flap
      and on-flap epipolis laser in situ keratomileusis (epi-LASIK) for myopia.
      METHODS: Pertinent studies were selected by extensive searches. A total of 9
      studies reporting on a total of 958 eyes were included in the present meta
      analysis. Statistical analysis was performed using RevMan 5.0 software. RESULTS:
      There were no significant differences in the final refractive spherical
      equivalent (p = 0.38), manifest refractive spherical equivalent within +/-0.50 D
      of the target (p = 0.76), final uncorrected visual acuity (p = 0.90), loss of >=1
      line of best spectacle-corrected visual acuity (p = 0.99), and corneal haze at 3
      months postoperatively (p = 0.96) or more than 6 months (p = 0.64). More patients
      felt severe pain in the on-flap group than in the off-flap group, although this
      finding was not statistically significant (p = 0.05). However, off-flap epi-LASIK
      had a better mean uncorrected visual acuity at 3 days (p = 0.04) and 5 days (p =
      0.01), and faster re-epithelialization (p < 0.00001) after surgery. CONCLUSIONS:
      According to the available data, off-flap and on-flap epi-LASIK had equal visual
      and refractive outcomes for the treatment of myopia. Off-flap epi-LASIK had more
      rapid re-epithelialization and visual recovery compared to on-flap epi-LASIK.

PMID- 21952500
TI  - Structure-function relationships using the Cirrus spectral domain optical
      coherence tomograph and standard automated perimetry.
AB  - PURPOSE: To evaluate the relationship between glaucomatous structural damage
      assessed by the Cirrus Spectral Domain OCT (SDOCT) and functional loss as
      measured by standard automated perimetry (SAP). METHODS: Four hundred twenty-two
      eyes (78 healthy, 210 suspects, 134 glaucomatous) of 250 patients were recruited
      from the longitudinal Diagnostic Innovations in Glaucoma Study and from the
      African Descent and Glaucoma Evaluation Study. All eyes underwent testing with
      the Cirrus SDOCT and SAP within a 6-month period. The relationship between
      parapapillary retinal nerve fiber layer thickness (RNFL) sectors and
      corresponding topographic SAP locations was evaluated using locally weighted
      scatterplot smoothing and regression analysis. SAP sensitivity values were
      evaluated using both linear as well as logarithmic scales. We also tested the fit
      of a model (Hood) for structure-function relationship in glaucoma. RESULTS:
      Structure was significantly related to function for all but the nasal thickness
      sector. The relationship was strongest for superotemporal RNFL thickness and
      inferonasal sensitivity (R(2)=0.314, P<0.001). The Hood model fitted the data
      relatively well with 88% of the eyes inside the 95% confidence interval predicted
      by the model. CONCLUSIONS: RNFL thinning measured by the Cirrus SDOCT was
      associated with correspondent visual field loss in glaucoma.

PMID- 21952501
TI  - Cortical and hippocampal atrophy in patients with autosomal dominant familial
      Alzheimer's disease.
AB  - BACKGROUND: Both familial and sporadic Alzheimer's disease (AD) result in
      progressive cortical and subcortical atrophy. Familial autosomal dominant AD
      (FAD) allows us to study AD brain changes presymptomatically. METHODS: 33
      subjects at risk for FAD (25 for PSEN1 and 8 for APP mutations; 22 mutation
      carriers and 11 controls) and 3 demented PSEN1 mutation carriers underwent T(1)
      weighted MPRAGE 1.5T MRI. Using the hippocampal radial distance and cortical
      pattern matching techniques, we investigated the effects of carrier status and
      dementia diagnosis on cortical and hippocampal atrophy. All analyses were
      corrected for age and relative age (years to median age of disease onset in the
      family). RESULTS: The dementia cases had pronounced cortical atrophy in the
      lateral and medial parietal, posterior cingulate and frontal cortices and
      hippocampal atrophy bilaterally relative to both nondemented carriers and
      controls. Nondemented carriers did not show significant cortical thinning or
      hippocampal atrophy relative to controls. CONCLUSIONS: FAD is associated with
      thinning of the posterior association and frontal cortices and hippocampal
      atrophy. Larger sample sizes may be necessary to reliably identify cortical
      atrophy in presymptomatic carriers.

PMID- 21952502
TI  - The eldercare factory.
AB  - Rapid advances in service robotics together with dramatic shifts in population
      demographics have led to the notion that technology may be the answer to our
      eldercare problems. Robots are being developed for feeding, washing, lifting,
      carrying and mobilising the elderly as well as monitoring their health. They are
      also being proposed as a substitute for companionship. While these technologies
      could accrue major benefits for society and empower the elderly, we must balance
      their use with the ethical costs. These include a potential reduction in human
      contact, increased feeling of objectification and loss of control, loss of
      privacy and personal freedom as well as deception and infantilisation. With
      appropriate guidelines in place before the introduction of robots en masse into
      the care system, robots could improve the lives of the elderly, reducing their
      dependence and creating more opportunities for social interaction. Without
      forethought, the elderly may find themselves in a barren world of machines, a
      world of automated care: a factory for the elderly.

PMID- 21952504
TI  - Hierarchically structured nanocrystalline hydroxyapatite assembled hollow fibers
      as a promising protein delivery system.
AB  - Nanocrystalline hydroxyapatite assembled hollow fibers (NHAHF) in the membrane
      form were fabricated by combining the electrospinning technique and the
      hydrothermal method. This novel hierarchical tubular structure of hydroxyapatite
      exhibited excellent protein loading capacity and long-term sustained release
      property.

PMID- 21952505
TI  - Dual-functional ZnO nanorod aggregates as scattering layer in the photoanode for
      dye-sensitized solar cells.
AB  - A bilayered ZnO photoanode was constructed for dye-sensitized solar cells with a
      high conversion efficiency of 4.0%. One layer made of ZnO nanocrystallites
      increases dye adsorption, and the other consisting of ZnO nanorod aggregates
      provides a directed electron pathway for the electron transport together with a
      prominent aggregation-induced light scattering.

PMID- 21952507
TI  - Nonlinear optical properties in a nanoring: quantum size and magnetic field
      effect.
AB  - We have studied the nonlinear optical absorption and the nonlinear optical
      rectification of an exciton in a nanoring in the presence of magnetic flux. The
      calculation results show that one can control the properties of nonlinear optical
      absorption and nonlinear optical rectification of a nanoring by tuning the outer
      and inner radius. Moreover, we find that the nonlinear optical properties of a
      nanoring can be modulated by the magnetic flux through the nanoring.

PMID- 21952506
TI  - Synthesis and photophysical characterization of highly luminescent silica films
      doped with substituted 2-hydroxyphthalamide (IAM) terbium complexes.
AB  - Innovative Tb(3+) antenna complexes employing two different substituted 2
      hydroxyphthalamide ligands (HxOH-IAM and bis-HxOH-IAM) acting simultaneously as
      coordinating sites and light collector units have been synthesized and
      successively anchored in silica layers by the sol-gel technique. The complexes
      show remarkable photoluminescence (PL) quantum yields in methanol solution, as
      high as 0.30 and 0.40 for (HxOH-IAM)(4)?Tb(3+) and (bis-HxOH-IAM)(2)?Tb(3+),
      respectively. The grafting of the Tb(3+) complexes in silica single layers
      accomplished by exploiting the terminal hydroxyl groups of the IAM chains results
      in highly transparent and homogeneous films displaying bright green emission and
      PL efficiencies of up to 0.40. The silica layers containing the (bis-HxOH
      IAM)(2)?Tb(3+) show remarkable photostability even under prolonged and continuous
      irradiation (up to 3.5 h). The nature of the IAM ligands allows the
      photoexcitation of the complexes at wavelengths even longer than 350 nm, which is
      a spectral window suitable to develop luminescent lanthanide probes dedicated to
      bioanalyses and bioimaging applications.

PMID- 21952508
TI  - Only 11 of 91 countries meet WHO standard on air quality.

PMID- 21952509
TI  - High cost of cancer treatment doesn't reflect benefits, say specialists.

PMID- 21952510
TI  - Adipokine expression in brown and white adipocytes in response to hypoxia.
AB  - BACKGROUND: Adipose tissue has emerged as an important endocrine regulator by
      secreting hormones referred to as adipokines. Recent studies showed that adipose
      tissue considerably responds to hypoxia. Although the impact of white adipose
      tissue on regulative processes is established, the importance of brown adipose
      tissue in adults has emerged just recently. METHODS: Brown (BA) and white
      adipocytes (WA) were cultured either in the presence of chemical hypoxia-mimetics
      or under hypoxic atmosphere of 1% oxygen. Expression of hypoxia-inducible factor
      1alpha (HIF- 1alpha) was assessed by western blot. The expression levels of
      several known HIF-1alpha-regulated proteins [vascular endothelial growth factor
      (VEGF), leptin, adiponectin, and angiotensinogen (AGT)] were quantified. RESULTS:
      Both chemical hypoxia-mimetics and physical hypoxia led to increased nuclear HIF
      1alpha expression and to decreased cytoplasmatic adiponectin in both cell types.
      In contrast, VEGF and AGT expression did not change upon hypoxic stimulation.
      Leptin was exclusively detectable in WA, while uncoupling-protein 1 (UCP-1) was
      expressed in BA only. CONCLUSIONS: WA and BA are sensitive to hypoxia, in which
      HIF-1alpha expression is induced. Protein expression of adiponectin is hypoxia
      dependent, whereas AGT, VEGF, leptin, and UCP-1 expression do not change
      secondary to hypoxia.

PMID- 21952511
TI  - Fluorescent coronene monoimide gels via H-bonding induced frustrated dipolar
      assembly.
AB  - Two stage self-assembly of novel coronene monoimide (CMI) based gels that results
      in resurfacing of monomer emission in the aggregated state is reported. This
      process is attributed to a frustrated head-head dipolar assembly forced by
      hydrogen bonding.

PMID- 21952513
TI  - Oxygen sensing in retinal health and disease.
AB  - The retina has a uniquely high metabolic demand for oxygen that is normally met
      by a highly efficient vascular supply. Oxygen plays an essential role in
      oxidative phosphorylation as an electron acceptor in the mitochondrial
      respiratory chain in the synthesis of adenosine triphosphate required to support
      the metabolic demand, including that of the visual cycle. Maintenance of normal
      retinal function depends on a continuous supply of oxygen and on the capability
      to detect and respond rapidly to local oxygen deficiency (hypoxia). The
      functional reserve of oxygen is small and retinal hypoxia can cause neuroretinal
      dysfunction and degeneration that lead directly to vision loss. Local oxygen
      sensing mechanisms control adaptive responses that can help protect against
      ischaemic injury. In the retina, powerful oxygen sensing mechanisms rapidly
      detect alterations in intracellular oxygen tension and respond with adaptive
      changes that redress the balance between oxygen supply and demand. These
      responses include rapid changes in blood flow, protective metabolic adaptations
      and angiogenesis. In the eye, however, the angiogenic response to hypoxia is
      typically associated with oedema, haemorrhage and fibrosis that can exacerbate
      hypoxic neuroretinal injury, causing severe vision loss. This aberrant response
      is the target of novel therapies including inhibitors of vascular endothelial
      growth factor. However, non-specific angiostatic agents fail to consider
      appropriate beneficial adaptive responses to hypoxia, and risk compromising
      neuroprotective mechanisms. In this review, we discuss the current understanding
      of retinal oxygenation and oxygen sensing in health and disease, focussing on the
      central role of hypoxia-inducible transcription factors, and suggest that
      therapeutic strategies may be improved by considering more targeted
      interventions.

PMID- 21952514
TI  - Target-selective photodegradation of oligosaccharides by a fullerene-boronic acid
      hybrid upon visible light irradiation.
AB  - A fullerene derivative was found to be capable of photodegrading oligosaccharides
      under irradiation with not only UV but also visible light. Furthermore, target
      selective photodegradation of oligosaccharides (beta-D-galactofuranosides) was
      achieved by a designed and synthesized fullerene-boronic acid hybrid upon
      irradiation with visible light in the absence of any additives under neutral
      conditions.

PMID- 21952515
TI  - Lewis acid fragmentation of a lithium aryloxide cage: generation of new
      heterometallic aluminium-lithium species.
AB  - Heterometallic aluminium-lithium species were prepared by the fragmentation
      reaction of the hexametallic cage compound [Li{2,6-(MeO)(2)C(6)H(3)O}](6) (1)
      with alkyl aluminium derivatives. Depending on the aluminium precursor, the
      species formed present different nuclearities in the solid state as shown by
      single crystal X-ray analysis. Spectroscopic and computational studies have been
      performed to study the nuclearity of the synthesized compounds in solution.

PMID- 21952516
TI  - A Zn4O-containing doubly interpenetrated porous metal-organic framework for
      photocatalytic decomposition of methyl orange.
AB  - A doubly interpenetrated semiconducting MOF Zn(4)O(2,6
      NDC)(3)(DMF)(1.5)(H(2)O)(0.5).4DMF.7.5H(2)O (UTSA-38) of a cubic net has been
      constructed, which exhibits photocatalytic activity for the degradation of methyl
      orange in aqueous solution.

PMID- 21952518
TI  - Plasma C-terminal pro-endothelin-1 and the natriuretic pro-peptides NT-proBNP and
      MR-proANP in very preterm infants with patent ductus arteriosus.
AB  - BACKGROUND: In very preterm infants, clinical decision-making, such as closing a
      patent ductus arteriosus (PDA), may be aided by measuring circulating natriuretic
      and endothelial pro-peptides. OBJECTIVES: To investigate the association between
      perinatal characteristics, PDA echocardiography and plasma concentrations of
      stable pro-peptides of B-type natriuretic peptide (NT-proBNP), atrial natriuretic
      peptide (MR-proANP) and endothelin-1 (CT-proET-1). METHODS: A prospective, cross
      sectional, single-center study was performed in 66 infants who were less than 32
      weeks of gestational age. Pro-peptide concentrations were determined at birth and
      at day 2-3 of life. RESULTS: Plasma concentrations of all 3 pro-peptides
      increased on average 2- to 5-fold from birth to day 2-3 of life. NT-proBNP and MR
      proANP were closely related at birth and at day 2-3 (Rs 0.902 and 0.897,
      respectively, p < 0.001), whereas CT-proET-1 was related to NT-proBNP and MR
      proANP at birth (Rs 0.478 and 0.460, respectively, p < 0.001) but not at day 2-3.
      Birth weight was negatively related to all 3 pro-peptides at birth (p < 0.01);
      however, preeclampsia and compromised placental perfusion were associated with
      elevated NT-proBNP and MR-proANP concentrations at birth. At day 2-3, MR-proANP
      and NT-proBNP correlated significantly with the ductal diameter (Rs 0.416 and
      0.415, respectively, both p = 0.011), whereas CT-proET-1 correlated with the left
      atrium/aorta ratio (Rs 0.506, p = 0.027). CT-proET-1 was elevated in infants with
      treated compared to untreated PDA [median (5-95% range) 388 (272-723) vs. 303
      (152-422) pmol/l, p = 0.011], but not NT-proBNP or MR-proANP. CONCLUSION: CT
      proET-1 is a promising predictor in determining the need for PDA intervention.

PMID- 21952519
TI  - Selective one-step synthesis of triple-decker (porphyrinato)(phthalocyaninato)
      early lanthanides: the balance of concurrent processes.
AB  - An effective one-step approach for the preparation of
      (porphyrinato)(phthalocyaninato) early lanthanides of type
      [Br(4)TPP]Ln[(15C5)(4)Pc]Ln[Br(4)TPP], where Br(4)TPP = 5,10,15,20-tetrakis-(4
      bromophenyl)-porphyrinato-ligand, (15C5)(4)Pc = tetrakis-(15-crown-5)
      phthalocyaninato-ligand and Ln = La, Pr, Nd or Eu, is developed. The influence of
      various factors on the reaction pathway and yields of the complexes is
      investigated in detail. The developed protocol is found to be general for the
      early lanthanide subgroup. Variation of the synthetic conditions allowed the
      determination and isolation of possible side-products, namely heteroleptic double
      deckers [Br(4)TPP]Ln[(15C5)(4)Pc] (Ln = Nd, Eu) and triple-decker
      [Br(4)TPP]Nd[(15C5)(4)Pc]Nd[(15C5)(4)Pc]. The peculiarities of the NMR lanthanide
      induced shifts (LIS) of resonances of the synthesized triple-decker complexes are
      precisely investigated. The isostructurality of the synthesized complexes within
      the series as well as isostructurality with previously synthesized compounds is
      demonstrated in terms of two-nuclei analysis of LIS.

PMID- 21952520
TI  - Seeded growth of two-dimensional dendritic gold nanostructures.
AB  - We show that seeded growth can be applied to creating two-dimensional (2D)
      dendritic Au nanostructures on sample grids, which can be directly characterized
      by transmission electron microscopy (TEM). The 2D synthesis of highly consistent
      structures offers a novel mechanistic perspective on the aggregation of colloidal
      Au nanocrystals on a surface.

PMID- 21952521
TI  - Bacterial contamination and the transport vial material affect cerebrospinal
      fluid concentrations of beta-Amyloid and Tau protein as determined by enzyme
      immunoassay.
AB  - BACKGROUND/AIMS: Determination of marker proteins of neuronal degeneration in
      cerebrospinal fluid (CSF) is of increasing importance. However, preanalytical
      problems may compromise the results. METHODS: We studied the influence of the
      transport tube material and shaking at room temperature on the CSF concentrations
      of beta-amyloid and tau protein determined by enzyme immunoassays. RESULTS: The
      materials of the transport tube moderately influenced the CSF concentrations of
      beta-amyloid and tau protein. Polyethylene and polypropylene tubes were well
      suited, but glass, polycarbonate and polystyrene tubes caused a decrease in the
      CSF beta-amyloid and tau protein concentrations. The strongest impact, however,
      was caused by bacterial contamination of samples. Contamination with high
      concentrations of Pseudomonas aeruginosa and related species rendered beta
      amyloid undetectable and strongly diminished tau protein concentrations. The
      effects of several Gram-positive bacteria were less pronounced. Addition of 0.1%
      sodium azide prior to bacterial contamination increased the interval at which CSF
      could be kept at room temperature without a substantial reduction of the beta
      amyloid or tau protein concentration. CONCLUSION: Polyethylene or polypropylene
      tubes are suitable transport vessels for CSF samples. Bacterial contamination
      during sampling and portioning must be avoided. Addition of sodium azide may be
      an option when transport of the sample is delayed.

PMID- 21952522
TI  - Digital ocular fundus imaging: a review.
AB  - Ocular fundus imaging plays a key role in monitoring the health status of the
      human eye. Currently, a large number of imaging modalities allow the assessment
      and/or quantification of ocular changes from a healthy status. This review
      focuses on the main digital fundus imaging modality, color fundus photography,
      with a brief overview of complementary techniques, such as fluorescein
      angiography. While focusing on two-dimensional color fundus photography, the
      authors address the evolution from nondigital to digital imaging and its impact
      on diagnosis. They also compare several studies performed along the transitional
      path of this technology. Retinal image processing and analysis, automated disease
      detection and identification of the stage of diabetic retinopathy (DR) are
      addressed as well. The authors emphasize the problems of image segmentation,
      focusing on the major landmark structures of the ocular fundus: the vascular
      network, optic disk and the fovea. Several proposed approaches for the automatic
      detection of signs of disease onset and progression, such as microaneurysms, are
      surveyed. A thorough comparison is conducted among different studies with regard
      to the number of eyes/subjects, imaging modality, fundus camera used, field of
      view and image resolution to identify the large variation in characteristics from
      one study to another. Similarly, the main features of the proposed
      classifications and algorithms for the automatic detection of DR are compared,
      thereby addressing computer-aided diagnosis and computer-aided detection for use
      in screening programs.

PMID- 21952523
TI  - Transverse spin current in the s-wave/p-wave Josephson junction.
AB  - We report a theoretical study on spin transport in the hybrid Josephson junction
      composed of singlet s-wave and triplet p-wave superconductor. The node of the
      triplet pair potential is considered perpendicular to the interface of the
      junction. Based on a symmetry analysis, we predict that there is no net spin
      density at the interface of the junction but instead a transverse mode-resolved
      spin density can exist and a nonzero spin current can flow transversely along the
      interface of the junction. The predictions are numerically demonstrated by means
      of the lattice Matsubara Green's function method. It is also shown that, when a
      normal metal is sandwiched in between two superconductors, both spin current and
      transverse mode-resolved spin density are only residing at two interfaces due to
      the smearing effect of the multimode transport. Our findings are useful for
      identifying the pairing symmetry of the p-wave superconductor and generating spin
      current.

PMID- 21952524
TI  - Adiponectin, leptin, and resistin in patients with aortic stenosis without
      concomitant atherosclerotic vascular disease.
AB  - INTRODUCTION: Early stages of atherosclerosis and aortic stenosis (AS) are
      similar. Advanced coronary artery disease is characterized by altered profile of
      circulating adipocytokines. We hypothesized that plasma profile of adipocytokines
      is associated with the severity of AS. OBJECTIVES: The aim of the study was to
      evaluate the relationship between AS and adipocytokines. PATIENTS AND METHODS: In
      74 patients with AS without atherosclerosis and left ventricular ejection
      fraction above 50% (57 men, 17 women, aged 58 +/-9.1 years) and 74 controls,
      resistin, leptin, and adiponectin levels were determined by the Bio-Rad Luminex
      system. Aortic valve area indexed to body surface area (AVAI) as well as the mean
      and peak transvalvular pressure gradients (PG) were assessed by echocardiography.
      RESULTS: We observed similar adiponectin and leptin levels in patients with AS
      and controls (20.8 +/-7.9 vs. 20.4 +/-3.9 MUg/ml, P = 0.67 and 17.0 +/-6.4 vs.
      16.4 +/-5.9 ng/ml, P = 0.52, respectively). Twenty-one patients had mild, 21
      moderate, and 32 severe AS. After adjusting for age and the body mass index,
      adiponectin levels were 20.3 +/-0.5 MUg/ml in controls, 26.7 +/-0.9 MUg/ml in
      mild, 20.2 +/-0.9 MUg/ml in moderate, and 17.5 +/-0.7 MUg/ml in severe AS (P
      <0.001). Leptin levels were 16.4 +/-0.7 ng/ml in controls, 21.1 +/-1.3 ng/ml in
      mild, 16.9 +/-1.3 ng/ml in moderate, and 14.4 +/-1.1 ng/ml in severe AS (P =
      0.003). Adiponectin and leptin correlated with the AVAI (r = 0.70, P <0.001; r =
      0.37, P = 0.001; respectively), mean PG (r = -0.72, P <0.001; r = -0.27, P =
      0.009; respectively), and peak PG (r = -0.67, P <0.001; r = -0.23, P = 0.03;
      respectively). In a multivariable analysis, the mean PG was the only independent
      echocardiographic predictor of adiponectin levels (P <0.001), while the AVAI was
      the only independent echocardiographic predictor of leptin levels in AS patients
      (P = 0.049). CONCLUSIONS: Lower levels of adiponectin and leptin, but not
      resistin, are associated with severe AS, suggesting that adipocytokines may be
      involved in the progression of AS, and especially adiponectin, which plays a
      protective role in this process.

PMID- 21952525
TI  - Benefits of antihypertensive drugs when blood pressure is below 140/90 mmHg.
AB  - Antihypertensive medications are used to lower blood pressure (BP) but,
      ultimately, their true value lies in reductions in morbidity and mortality
      (cardiovascular, cerebrovascular, and renal diseases). Hypertension is defined
      discreetly (generally 140/90 mmHg) but the actual relationship between BP and
      adverse cardiac and cerebrovascular outcomes is continuous. Observational studies
      have demonstrated a powerful log-linear relationship between BP and mortality due
      to ischemic heart disease (IHD) or stroke over the range of 115/75 to 185/115
      mmHg. Clinical trials and meta-analyses have clearly demonstrated benefits of
      antihypertensive drugs in nonhypertensive individuals: delay or prevention of the
      onset of hypertension and microalbuminuria and reduced morbidity and mortality
      from IHD, stroke, and chronic kidney disease. This is not surprising given that
      various antihypertensive drug classes have multiple potential beneficial effects.
      A persistent concern is that overtreatment of hypertension may increase risk in
      individuals with coronary artery disease, but a "J-curve" effect is not
      consistently found in clinical studies. The use of antihypertensive drugs in at
      risk individuals who are below the traditional threshold (140/90 mmHg) is fully
      justifiable, but the decision requires adequate clinical experience and judgment
      and a full assessment of risks and benefits.

PMID- 21952526
TI  - Acquired dysfibrinogenemia in atherosclerotic vascular disease.
AB  - Acquired qualitative abnormalities of fibrinogen molecules, termed acquired
      dysfibrinogenemia, have been demonstrated in several disease states mostly
      related to prothrombotic tendency, including multiple myeloma and liver disease.
      Fibrin is abundant in atherosclerotic plaques. Altered plasma fibrin properties,
      reflected usually by reduced clot permeability and impaired fibrinolysis, have
      been reported in patients with acute or prior myocardial infarction, ischemic
      stroke, and peripheral artery disease. Moreover, prothrombotic clot phenotype has
      been observed in patients with previous no-reflow phenomenon and stent
      thrombosis. Growing evidence indicates that acquired dysfibrinogenemia
      contributes to the progression of atherosclerotic vascular disease and the
      occurrence of its thrombotic manifestations. The review summarizes current
      knowledge on the links between fibrin clot phenotype and atherosclerotic vascular
      disease and describes a wide spectrum of cardiovascular risk factors as modifiers
      of fibrin network characteristics.

PMID- 21952527
TI  - Iodobenzene catalysed synthesis of spirofurans and benzopyrans by oxidative
      cyclisation of vinylogous esters.
AB  - Vinylogous esters bearing para or meta methoxy benzyl groups undergo oxidative
      cyclisation with 5-20 mol% iodobenzene and m-CPBA to give spirofuran or
      benzopyran containing heterocycles. The reaction allows rapid generation of
      skeletal complexity in good to excellent yields via a novel oxidative
      cyclisation.

PMID- 21952529
TI  - Life-threatening hyponatremia and acute renal failure due to iatrogenic neonatal
      bladder rupture.
AB  - Neonatal urinary ascites is a rare entity, usually associated with a spontaneous
      rupture of the bladder with an underlying pathology such as high pressure or wall
      disruption. Its presentation involves abdominal distension, metabolic derangement
      and respiratory compromise. We report the case of a male neonate with solitary
      functioning kidney presented with life-threatening persistent hyponatremia and
      acute renal failure due to iatrogenic bladder rupture after catheterization. The
      aim of our report is to raise awareness on the possibility of bladder perforation
      in neonates even in the absence of technical faults. We discuss the uncommon
      presentation of our case and highlight the need for early recognition and
      management of urinary ascites, addressing all subspecialties involved in
      diagnostic or therapeutic procedures of neonates with urinary abnormalities.

PMID- 21952530
TI  - Design, synthesis and protein-targeting properties of thioether-linked hydrogen
      bond surrogate helices.
AB  - Appropriately-placed hydrogen bond surrogates have been demonstrated to
      efficiently nucleate helical conformations. Herein we describe an efficient
      method for the synthesis of thioether-based hydrogen bond surrogate (teHBS)
      helices. A teHBS helix is shown to adopt a stable conformation and target its
      cognate protein receptor with high affinity.

PMID- 21952531
TI  - Formation of a non-crystalline bimolecular porous network at a liquid/solid
      interface.
AB  - An equimolar mixture of two structurally related molecular building blocks self
      assembles into a 2D non-crystalline bimolecular porous pattern at a liquid-solid
      interface as revealed by scanning tunneling microscopy.

PMID- 21952532
TI  - Ratiometric luminescent molecular oxygen sensors based on uni-luminophores of C^N
      Pt(II)(acac) complexes that show intense visible-light absorption and balanced
      fluorescence/phosphorescence dual emission.
AB  - Uni-luminophores of C^N cyclometalated Pt(II) complexes with balanced room
      temperature fluorescence/phosphorescence dual emission were prepared for
      ratiometric oxygen sensing in both intensity mode and lifetime mode.

PMID- 21952533
TI  - Binding of citrus flavanones and their glucuronides and chalcones to human serum
      albumin.
AB  - Naringenin and hesperetin glycosides are the major polyphenols (flavanones) of
      citrus fruits and juices and are thought to participate in the cardioprotective
      effects of diets rich in plant products. Naringenin and hesperetin glucuronides
      (resulting from conjugation at the A- or B-ring) are the main circulating
      metabolites in humans and their binding to human serum albumin (HSA) is expected
      to modulate their half-life in plasma and tissue distribution. In this work, the
      binding of flavanone glucuronides to HSA was investigated by fluorescence
      spectroscopy. Binding constants in the range of 3-9 * 10(4) M(-1) were estimated.
      The affinity of glucuronides for HSA is close to that of naringenin and
      hesperetin themselves. Competition experiments in the presence of the fluorescent
      probes dansylsarcosine and quercetin were used to gain information on the
      flavanone binding site. Naringenin and hesperetin chalcones were also included
      for comparison as their glucuronides too were detected in the general
      circulation. Naringenin and hesperetin chalcones spontaneously undergo
      cyclization back to the parent flavanones under neutral conditions. The
      cyclization was significantly slowed down by HSA but led to a racemic mixture of
      (2R) and (2S) flavanones in the absence or presence of HSA.

PMID- 21952534
TI  - Initial proximal obstruction of ventriculoperitoneal shunt in patients with
      preterm-related posthaemorrhagic hydrocephalus.
AB  - BACKGROUND/AIMS: Obstruction is the most common complication of
      ventriculoperitoneal shunts in patients with hydrocephalus. Despite technical
      advances, rates of obstruction have barely decreased and remain at over 40% of
      cases. Patients suffering from preterm-related posthaemorrhagic hydrocephalus are
      considered a group with a particularly high risk of obstruction. The aim of the
      present study was to review our series of patients with preterm-related
      posthaemorrhagic hydrocephalus and analyse the occurrence of the first
      ventricular shunt obstruction as well as the related clinical and radiological
      factors. METHODS: We conducted a retrospective review of 103 cases treated from
      1982 to 2010. Descriptive analysis, raw and adjusted bivariate correlations and
      survival analysis were performed. RESULTS: Over the course of the follow-up, 42
      patients presented at least one episode of obstruction that required proximal
      revision. Medium-opening pressure valves were associated with a higher rate of
      obstruction compared to low-opening pressure valves; however, in our series this
      association became statistically significant only in patients with a weight of
      over 2,000 g at the time of surgery (odds ratio 6.75). The occurrence of previous
      infection and the development of late slit ventricle syndrome were also
      significantly associated with obstruction of the ventricular catheter (odds
      ratios 3.35 and 4.27, respectively). CONCLUSIONS: Rates of shunt obstruction in
      preterm-related posthaemorrhagic hydrocephalus remain high but do not seem to be
      higher than in other groups of paediatric hydrocephalus. Prevention of infection
      and the use of the appropriate type of valve design can help to decrease the
      incidence of proximal shunt obstruction, which in turn could decrease the
      incidence of symptomatic slit ventricle syndromes.

PMID- 21952535
TI  - Early postnatal surge of serum Clara cell secretory protein in newborn infants.
AB  - BACKGROUND: Clara cell secretory protein (CCSP) is an anti-inflammatory mediator,
      but its role in neonatal lung adaptation and diseases is uncertain. OBJECTIVE: To
      characterize postnatal changes in serum CCSP in relation to gestation,
      respiratory disease (RDS) and bronchopulmonary dysplasia (BPD) in comparison with
      other anti-inflammatory cytokines (IL-4, -10 and -13). METHODS: Blood was
      collected from 76 infants (26 of 23-29 weeks' gestation, 33 of 30-36 weeks'
      gestation and 17 term infants) at birth (preterm cord blood); on admission; at
      12, 24 and 48 h; and on days 3-4 and 7 of life. CCSP was assayed by ELISA and
      cytokines by Bio-Plex. RESULTS: Median serum CCSP in extremely and moderately
      preterm infants rose from a baseline of 13.6 and 15.9 to 33.4 ng/ml (p = 0.04)
      and 59.8 ng/ml (p = 0.03) at 12 h of age, respectively. CCSP levels were highest
      in term infants (80.7 ng/ml at 12 h). CCSP then decreased to 22.5 ng/ml on days 3
      4 (p = 0.001). CCSP of 37 RDS infants fell to a lower baseline on days 4 and 7
      than that of the 22 non-RDS preterms. The 8 infants who developed BPD had
      persistently low serum CCSP (12.7 ng/ml at 12 h). In contrast, early postnatal
      changes were not seen in IL-4, -10 and -13 levels, but low IL-10 and -13 levels
      were found on day 7 in BPD infants. CONCLUSIONS: Serum CCSP levels were
      characterized by an early postnatal surge. This apparent gestation-influenced
      surge may represent an initiation of a protective cascade against postnatal lung
      injury during extrauterine adaptation.

PMID- 21952536
TI  - Enhancement of local superconductivity in ferromagnetic FeCrB metallic glass by
      Ar+ ion irradiation.
AB  - We have reinforced local superconductivity in ferromagnetic Fe(67)Cr(18)B(15)
      metallic glasses by ion irradiation. Superconductivity in this medium appears due
      to the presence of large-scale layered clusters of metallic Fe-Cr phase, 150-230
      A in size, with a ferromagnetic (or superparamagnetic) Fe-rich core and
      nonmagnetic Cr-rich superconducting shell. Here we show that due to the
      intensification of concentration phase separation in the Fe-Cr clusters under ion
      (Ar(+)) irradiation, the volume of the superconducting phase increases from the
      initial 0.4-0.5% up to 7-8%. After irradiation, the resistivity jump Deltarho/rho
      in the temperature range T=3.1-3.6 K increases ~14 times, reaching 19%, as
      compared to 1.36% for the initial sample. In the interval of T=3.1-3.6 K, the
      rate of resistance change reaches 79% K(-1) for the irradiated sample instead of
      3.6% K(-1) for the initial sample. In the same temperature interval, the rate of
      magnetoresistance change increases from 3% K(-1) for the initial sample up to 70%
      K(-1) after irradiation.

PMID- 21952537
TI  - Regional differences in effects of APOE epsilon4 on cognitive impairment in non
      demented subjects.
AB  - BACKGROUND: The APOE epsilon4 allele is a risk factor for Alzheimer's disease
      (AD). APOE epsilon4 is common in non-demented subjects with cognitive impairment.
      In both healthy people and people with AD, its prevalence has a north-south
      gradient across Europe. In the present study, we investigated whether the
      relation between the APOE epsilon4 allele and cognitive impairment varied across
      Northern, Middle and Southern Europe. We also investigated whether a north-south
      gradient existed in subjects with subjective cognitive impairment (SCI), amnestic
      mild cognitive impairment (MCI) and non-amnestic MCI. METHODS: Data from 16
      centers across Europe were analyzed. RESULTS: A north-south gradient in APOE
      epsilon4 prevalence existed in the total sample (62.7% for APOE epsilon4 carriers
      in the northern region, 42.1% in the middle region, and 31.5% in the southern
      region) and in subjects with SCI and amnestic MCI separately. Only in Middle
      Europe was the APOE epsilon4 allele significantly associated with poor
      performance on tests of delayed recall and learning, as well as with the amnestic
      subtype of MCI. CONCLUSION: The APOE epsilon4 allele frequencies in subjects with
      SCI and amnestic MCI have a north-south gradient. The relation between the APOE
      epsilon4 allele and cognition is region dependent.

PMID- 21952538
TI  - Genome sequence of Cronobacter sakazakii E899, a strain associated with human
      illness.
AB  - Cronobacter has caused numerous illnesses in neonates, infants, and children.
      Here we report the draft genome of Cronobacter sakazakii E899. Whole-genome
      sequence analysis of Cronobacter strains provides a tool for understanding the
      genomic regions specific to each individual species.

PMID- 21952539
TI  - The genome of the plant growth-promoting rhizobacterium Paenibacillus polymyxa M
      1 contains nine sites dedicated to nonribosomal synthesis of lipopeptides and
      polyketides.
AB  - The genome of Paenibacillus polymyxa M-1 consisted of a 5.8-Mb chromosome and a
      360-kb plasmid. Nine sites were dedicated to nonribosomal synthesis of
      lipopeptides and polyketides. Eight of them were located at the chromosome, while
      one gene cluster predicted to encode an unknown secondary metabolite was present
      on the plasmid.

PMID- 21952540
TI  - Draft genome sequence of Sporolactobacillus inulinus strain CASD, an efficient D
      lactic acid-producing bacterium with high-concentration lactate tolerance
      capability.
AB  - Sporolactobacillus inulinus CASD is an efficient D-lactic acid producer with high
      optical purity. Here we report for the first time the draft genome sequence of S.
      inulinus (2,930,096 bp). The large number of annotated two-component system genes
      makes it possible to explore the mechanism of extraordinary lactate tolerance of
      S. inulinus CASD.

PMID- 21952541
TI  - Genome sequence of the Mycobacterium colombiense type strain, CECT 3035.
AB  - We report the first whole-genome sequence of the Mycobacterium colombiense type
      strain, CECT 3035, which was initially isolated from Colombian HIV-positive
      patients and causes respiratory and disseminated infections. Preliminary
      comparative analyses indicate that the M. colombiense lineage has experienced a
      substantial genome expansion, possibly contributing to its distinct pathogenic
      capacity.

PMID- 21952542
TI  - Genome sequence of Weissella thailandensis fsh4-2.
AB  - Weissella thailandensis fsh4-2 is a heterofermentative lactic acid bacterium
      isolated from the Korean fermented seafood condiment jeotkal. Here we report the
      draft genome sequence of W. thailandensis fsh4-2 (1,651 genes, 1,436 encoding
      known proteins, 183 encoding unknown proteins, 32 RNA genes), which consists of
      50 large contigs of >100 bp.

PMID- 21952543
TI  - Genome sequence of Thermotoga sp. strain RQ2, a hyperthermophilic bacterium
      isolated from a geothermally heated region of the seafloor near Ribeira Quente,
      the Azores.
AB  - Thermotoga sp. strain RQ2 is probably a strain of Thermotoga maritima. Its
      complete genome sequence allows for an examination of the extent and consequences
      of gene flow within Thermotoga species and strains. Thermotoga sp. RQ2 differs
      from T. maritima in its genes involved in myo-inositol metabolism. Its genome
      also encodes an apparent fructose phosphotransferase system (PTS) sugar
      transporter. This operon is also found in Thermotoga naphthophila strain RKU-10
      but no other Thermotogales. These are the first reported PTS transporters in the
      Thermotogales.

PMID- 21952544
TI  - Complete genome sequence of type strain Campylobacter fetus subsp. venerealis
      NCTC 10354T.
AB  - Campylobacter fetus subsp. venerealis is the etiologic agent of bovine genital
      campylobacteriosis, a sexually transmitted disease of cattle that is of worldwide
      importance. The complete sequencing and annotation of the genome of the type
      strain C. fetus subsp. venerealis NCTC 10354(T) are reported.

PMID- 21952545
TI  - Genome sequence of the human pathogen Vibrio cholerae Amazonia.
AB  - Vibrio cholerae O1 Amazonia is a pathogen that was isolated from cholera-like
      diarrhea cases in at least two countries, Brazil and Ghana. Based on multilocus
      sequence analysis, this lineage belongs to a distinct profile compared to strains
      from El Tor and classical biotypes. The genomic analysis revealed that it
      contains Vibrio pathogenicity island 2 and a set of genes related to pathogenesis
      and fitness, such as the type VI secretion system, present in choleragenic V.
      cholerae strains.

PMID- 21952546
TI  - Genome sequences for five strains of the emerging pathogen Haemophilus
      haemolyticus.
AB  - We report the first whole-genome sequences for five strains, two carried and
      three pathogenic, of the emerging pathogen Haemophilus haemolyticus. Preliminary
      analyses indicate that these genome sequences encode markers that distinguish H.
      haemolyticus from its closest Haemophilus relatives and provide clues to the
      identity of its virulence factors.

PMID- 21952547
TI  - Genome sequence of the marine photoheterotrophic bacterium Erythrobacter sp.
      strain NAP1.
AB  - Here we report the full genome sequence of marine phototrophic bacterium
      Erythrobacter sp. strain NAP1. The 3.3-Mb genome contains a full set of
      photosynthetic genes organized in one 38.9-kb cluster; however, it does not
      contain genes for CO(2) or N(2) fixation, thereby confirming that the organism is
      a photoheterotroph.

PMID- 21952548
TI  - Genome sequence of duck pathogen Mycoplasma anatis strain 1340.
AB  - Mycoplasma anatis, a member of the class Mollicutes, is the causative agent of a
      contagious infectious disease of domestic ducklings, wild birds, and eggs.
      Increasing reports show that coinfection of M. anatis with Escherichia coli
      results in substantial economic impacts on the duck farms in China. Here, we
      announce the first genome sequence of M. anatis.

PMID- 21952549
TI  - Patient safety dialogue:  evaluation of an intervention aimed at achieving an
      improved patient safety culture.
AB  - OBJECTIVES: Patient Safety Dialogue, a local intervention inspired by walk round
      style approaches, was implemented in 2005 in a Swedish county council to achieve
      a positive patient safety culture in health care. This paper evaluates the
      results and changes after 5 years of the Patient Safety Dialogue in 50
      departments (37 medical and 13 psychiatric) in 3 hospitals. METHODS: The patient
      safety culture maturity was rated on 5 levels that correspond with the Manchester
      Patient Safety Assessment Framework. The assessment was based on information
      supplied by the departments and discussions between clinical leaders and staff
      members with special patient safety assignments and representatives from a
      patient safety unit. Three patient safety areas were assessed: hospital-acquired
      infections, outcome measurements, and general patient safety. Each department was
      assessed 3 times: at baseline and at follow-ups at 18 and 36 months. Average
      scores were calculated for each of the 3 safety areas on all occasions. The
      departments were classified into 3 types of trajectories on the basis of the
      development of their scores over time. RESULTS: More than two-thirds of the
      departments attained higher scores in round 3 than in round 1. Seventy-eight
      percent of the departments in the general patient safety area were categorized as
      continuously improving or developing, compared with 68% for outcome measurement
      and 50% for hospital-acquired infection. Approximately one-third was categorized
      as nonimproving, with scores in round 3 lower than or equal to the scores in
      round 1. The medical departments had higher scores than the psychiatric
      departments in all rounds. CONCLUSIONS: Most of the 50 departments were evaluated
      to have improved their patient safety culture during the 5 years of the Patient
      Safety Dialogue, suggesting that the intervention is effective in supporting an
      improved patient safety culture. However, one-third of the departments did not
      improve during the 5-year study period.

PMID- 21952551
TI  - A hybrid nanostructure of platinum-nanoparticles/graphitic-nanofibers as a three
      dimensional counter electrode in dye-sensitized solar cells.
AB  - We directly synthesized a platinum-nanoparticles/graphitic-nanofibers
      (PtNPs/GNFs) hybrid nanostructure on FTO glass. We applied this structure as a
      three-dimensional counter electrode in dye-sensitized solar cells (DSSCs), and
      investigated the cells' photoconversion performance.

PMID- 21952552
TI  - A copper(II) rhodamine complex with a tripodal ligand as a highly selective
      fluorescence imaging agent for nitric oxide.
AB  - A copper(II) complex CuRBT with a ring-closed rhodamine-containing tripodal
      ligand was synthesized as a highly selective fluorescent imaging agent for nitric
      oxide (NO). It featured a 700-fold fluorescent enhancement toward NO from a dark
      background with the detection limit of NO about 1 nM in aqueous solution and
      could be applied for monitoring intracellular NO.

PMID- 21952553
TI  - Reassessment of sst(5) somatostatin receptor expression in normal and neoplastic
      human tissues using the novel rabbit monoclonal antibody UMB-4.
AB  - OBJECTIVE: The frequent overexpression of somatostatin receptors (sst) in
      neuroendocrine tumors provides the molecular basis for the diagnostic and
      therapeutic application of stable somatostatin analogs. Whereas octreotide acts
      mainly via the sst(2) receptor, the novel pan-somatostatin analog pasireotide
      exhibits particular high affinity for the sst(5) receptor. To determine whether a
      patient is a candidate for octreotide or pasireotide therapy, it is important to
      evaluate the somatostatin receptor status. However, so far highly specific rabbit
      monoclonal antibodies have been developed for the sst(2) receptor only (clone UMB
      1). METHODS: Here, we have extensively characterized a novel rabbit monoclonal
      antibody for the human sst(5) receptor (clone UMB-4). In a comparative
      immunohistochemical study, the expression of sst(5) and sst(2) receptors was
      assessed using UMB-4 and UMB-1, respectively. RESULTS: Western blot experiments
      unequivocally demonstrated that UMB-4 selectively detected its cognate sst(5)
      receptor and did not cross-react with other proteins present in crude tissue
      homogenates. UMB-4 yielded a highly effective immunostaining of distinct cell
      populations in formalin-fixed, paraffin-embedded human tissues with a
      predominance of plasma membrane staining. In the pituitary, sst(5) was present on
      all growth hormone (GH)- and adrenocorticotropin hormone (ACTH)-producing cells
      whereas sst(2) was only observed on a subpopulation of GH-positive cells.
      Consequently, sst(5) was detectable on the majority of GH and ACTH adenomas. In
      contrast, sst(2) was only seen on GH but not on ACTH adenomas. CONCLUSIONS: The
      rabbit monoclonal antibodies UMB-4 and UMB-1 will facilitate the assessment of
      the somatostatin receptor status of human tumors during routine histopathological
      examinations.

PMID- 21952554
TI  - Retinoic acid rescues deficient airway innervation and peristalsis of hypoplastic
      rat lung explants.
AB  - BACKGROUND: Bronchial peristalsis modulates lung growth and is deficient in
      hypoplastic nitrofen-exposed rat lung explants. Retinoic acid (RA) rescues lung
      hypoplasia. This study examines whether decreased bronchial innervation
      contributes to this developmental deficiency and if RA is able to recover
      bronchial innervation and motility. MATERIAL AND METHODS: After IRB approval,
      pregnant rats received either 100 mg nitrofen or vehicle on gestational day 9.5
      (E9.5). Embryonic lung primordia harvested on E13 were cultured for 72 h and RA
      was added daily to the medium when appropriate. Lung growth was assessed by
      counting the number of terminal buds and measuring explant surface, total DNA and
      protein in control, control + RA, nitrofen and nitrofen + RA groups. Peristaltic
      contractions were recorded for 10 min under an inverted microscope. Lung explants
      stained for anti-protein gene product 9.5 (PGP 9.5) and smooth muscle alpha-actin
      were examined under a confocal microscope for depicting the specific relationship
      between neural and smooth muscle cells. PGP 9.5 and smooth muscle alpha-actin
      levels were quantified by Western blot analysis for assessing the neural and
      muscle cell expressions. Comparisons between groups were made with non-parametric
      tests. RESULTS: The number of terminal buds, the explants' surface and the DNA
      and protein contents were significantly decreased in nitrofen-exposed lungs in
      comparison with controls. In contrast, these measurements were normal in explants
      exposed to both nitrofen and RA. Bronchial peristalsis (contractions/min) was
      significantly decreased in nitrofen-exposed lungs in comparison with controls; in
      contrast, in nitrofen + RA lungs it was similar to controls. In all study groups,
      the airways were surrounded by smooth muscle and ensheathed in a plexus of nerve
      fibers containing ganglia. PGP 9.5 protein levels were decreased in nitrofen
      exposed lungs, but they normalized when RA was added. No differences were found
      in alpha-actin protein levels. Explants exposed only to RA were similar to
      control. CONCLUSIONS: Lung growth, bronchial innervation and peristalsis are
      decreased in nitrofen-exposed lung explants and are rescued by RA. If deficient
      airway innervation contributing to dysmotility and pulmonary hypoplasia can be
      pharmacologically rescued, new relatively simple prenatal interventions could be
      envisioned.

PMID- 21952555
TI  - Lowbush blueberries inhibit scavenger receptors CD36 and SR-A expression and
      attenuate foam cell formation in ApoE-deficient mice.
AB  - Blueberries have recently been reported to reduce atherosclerotic lesion
      progression in apoE deficient (apoE(-/-)) mice. However, the underlying
      mechanisms are not fully understood. The objective of this study was to determine
      whether lowbush blueberries altered scavenger receptor expression and foam cell
      formation in apoE(-/-) mice. ApoE(-/-) mice were fed AIN-93 diet (CD) or CD
      formulated to contain 1% freeze-dried lowbush blueberries (BB) for 20 weeks. Gene
      expression and protein levels of scavenger receptor CD36 and SR-A in aorta and
      thioglycollate-elicited peritoneal macrophages (PM) were lower in mice fed BB (P
      < 0.05). In the second experiment, apoE(-/-) mice were fed CD or BB for 5 weeks.
      PM were collected and cultured. Gene expression and protein levels of CD36 and SR
      A were found to be lower in PM of BB fed mice (P < 0.05). In PM from BB fed mice,
      fewer oxLDL-induced foam cells were formed compared to those from mice fed CD.
      Gene expression and protein levels of PPARgamma were lower in the PM of BB fed
      mice (P < 0.05). Detectable isomers of hydroxyoctadecadienoic acids (HODEs) and
      hydroxyeicosatetraenoic acid (HETEs) were also lower in the PM of BB fed mice (P
      < 0.05 or P < 0.01). In conclusion, BB inhibited expression of the two major
      scavenger receptors CD36 and SR-A in PM of apoE(-/-) mice, at least in part
      through down-regulating PPARgamma and reducing its endogenous ligands HODEs and
      HETEs. We proposed that BB mediated reduction of scavenger receptor expression
      and attenuation of oxLDL-induced foam cell formation in PM of apoE(-/-) mice are
      important mechanisms of the athero-protective effects of BB.

PMID- 21952556
TI  - Thalidomide in 42 patients with prurigo nodularis Hyde.
AB  - The aim of this study was to describe the use of thalidomide in the treatment of
      prurigo nodularis Hyde (PNH) refractory to other treatments or in cases where
      other treatments cannot be used due to side effects. 77 medical records were
      retrospectively reviewed for the following data: sex, age, age at the beginning
      of thalidomide treatment, dermatological diagnosis, duration of the skin disease,
      previous treatments, indications for treatment with thalidomide, effect of
      treatment, duration of treatment with thalidomide, reasons for cessation of
      thalidomide treatment, and side effects. 54 patients had PNH. All patients were
      refractory to standard therapy or had side effects to treatment. 42 patients were
      treated with thalidomide and the majority of patients experienced clinical
      improvement. The most common reason for discontinuation of therapy was side
      effects, the most frequent being peripheral neuropathy and sedation. Thalidomide
      effectively treats PNH refractory to standard medications. However, physicians
      must be aware of possible side effects, especially peripheral neuropathy.

PMID- 21952557
TI  - Copper inducing Abeta42 rather than Abeta40 nanoscale oligomer formation is the
      key process for Abeta neurotoxicity.
AB  - Copper is known to be a critical factor in Alzheimer's disease (AD) pathogenesis,
      as it is involved in amyloid-beta (Abeta) peptide related toxicity. However, the
      relationship between neurotoxicity and Abeta peptide in the presence of copper
      remains unclear. The effect of copper has not been clearly differentiated between
      Abeta42 and Abeta40, and it is still debated whether copper-mediated
      neurotoxicity is due to reactive oxygen species (ROS) accumulation or other
      molecular mechanisms. Here, we describe that copper dramatically affects Abeta42
      aggregation and enhances Abeta42 cytotoxicity while it shows no significant
      effects on Abeta40. These phenomena are mainly because that the strong
      interactions between copper and Abeta42 lead to great conformation changes, and
      stabilize Abeta42 aggregates at highly toxic nanoscale oligomer stage, whereas
      copper shows no similar impact on Abeta40. We also propose a possible molecular
      mechanism that copper enhances Abeta42 cytotoxicity via perturbing membrane
      structure. Moreover, we test the effect of an analogue of copper, nickel, on
      Abeta aggregation and cytotoxicity, finding that nickel also enhances
      cytotoxicity via Abeta42 nanoscale oligomer formation. These results clarify that
      the copper-induced Abeta42 nanoscale oligomer formation is the key process for
      Abeta neurotoxicity, and suggest that disrupting the interactions between copper
      and Abeta42 peptide to inhibit nanoscale oligomerization process, deserves more
      attention in AD drug development.

PMID- 21952558
TI  - NO and O2 reactivities of synthetic functional models of nitric oxide reductase
      and cytochrome c oxidase.
AB  - Though nitric oxide reductase (NOR) and cytochrome c oxidase (CcO) have similar
      active sites, they exhibit quite different functions. While NOR reduces NO to
      N(2)O, CcO reduces O(2) to H(2)O. Further, CcO is reversibly inhibited by NO, the
      substrate for NOR, and NOR is reversibly inhibited by O(2), which is the
      substrate for CcO. Over the past decade several structural and functional models
      of these enzymes have been reported. The mimics have been used to understand the
      reaction mechanism of these enzymes and develop structure function correlations
      for these active sites. This article summarizes these recent developments with
      particular stress on the reactivities of functional mimics of CcO with NO and
      functional mimics of NOR with O(2).

PMID- 21952561
TI  - Evidence for altered anorectal function in irritable bowel syndrome patients with
      sleep disturbance.
AB  - BACKGROUND/AIMS: Sleep dysfunction is associated with altered gastrointestinal
      functioning and the presence of irritable bowel syndrome (IBS). We aimed to
      investigate whether sleep dysfunction would influence anorectal motility in IBS
      patients. METHODS: A total of 16 healthy volunteers and 15 IBS patients underwent
      anorectal manometry. The anorectal parameters included resting and squeeze
      sphincter pressure, sensory thresholds in response to balloon distension, and
      rectoanal inhibitory reflex. Sleep dysfunction was assessed by using the
      Pittsburgh Sleep Quality Index (PSQI). RESULTS: IBS patients had a lower
      threshold volume for urge (p = 0.04) and pain (p = 0.002) as compared with the
      controls. IBS patients with sleep dysfunction had a significantly lower threshold
      volume for urge (p = 0.04) and anal sphincter pressure for maximal squeeze (p =
      0.048) as compared with those without sleep dysfunction. In IBS patients, the
      PSQI score significantly correlated with threshold volume for first sensation (r
      = -0.55; p = 0.03), urge (r = -0.56; p = 0.03) and pain (r = -0.58; p = 0.03).
      CONCLUSIONS: IBS patients with sleep dysfunction are characterized by lower
      thresholds for rectal perception. Sleep disturbance might be associated with
      anorectal dysfunction and appears to create some degree of rectal hyperalgesia in
      patients with IBS.

PMID- 21952560
TI  - Potential treatment of hypoparathyroidism with recombinant plasmids encoding
      preproparathyroid hormone.
AB  - Hypoparathyroidism cannot be cured by oral or intravenous calcium supplements.
      Using molecular biology techniques to induce the production of PTH is an ideal
      option to treat hypoparathyroidism. In this study, we established a recombinant
      plasmid encoding a mutant preproPTH with a skeletal muscle creatine kinase
      promoter (pCKM-mPTH). The sequence of the chimeric pCKM-mPTH gene was fully
      consistent with the DNA sequence reported previously and the site-directed
      mutagenesis was completed. Overlapping and nested PCR showed that PTH was highly
      expressed in and secreted from skeletal muscle cells transfected with the pCKM
      mPTH plasmid: the PTH concentration in the culture medium 24 h after transfection
      was 26.37 pg/l. In the rat hypoparathyroidism model, serum PTH level
      significantly increased after injection with the pCKM-mPTH plasmid, compared with
      control groups (p<0.01). The effect lasted for about 30 days. Our results
      indicated that the recombinant mutant pCKM-mPTH plasmid was successfully
      constructed and was highly expressed in skeletal muscle cells. In vivo, the
      plasmid was introduced successfully into rat muscles and could express PTH for a
      decent period of time.

PMID- 21952563
TI  - Cultural meaning of cancer suffering.
AB  - It is not possible to understand the cancer experience independent from the
      specific culture. The history, culture, related values, and traditions shape the
      experience of Turkish cancer patients. This article aims to review the current
      Turkish literature on the psychological and psychosocial effects of cancer and
      its related burden. The psychological and psychosocial burden of cancer is
      discussed. The review clearly documents that an interdisciplinary approach that
      combines oncologic and psychiatric treatments is required for decreasing the
      emotional, physiological, and social burden of cancer in Turkey.

PMID- 21952564
TI  - Impact of culture on the expression of pain and suffering.
AB  - A primary human challenge is how to alleviate suffering and loss. One way is
      through culture. The core characteristics of culture are symbols, sharing and
      groups. These three factors enable society to help the individual cope with loss.
      In the modern age traditional culture is disintegrating and is being replaced.
      Often it is outstanding individuals who provide the impetus and tools with which
      to change the culture and to adapt to new challenges. One lesson to be drawn from
      the discussion is the idea of using our culture more pro-actively to routinely
      contemplate loss, ageing and death.

PMID- 21952565
TI  - Unsteady balance:  the constraints of informal care.
AB  - The enduring cultural image of cancer is of an acute and deadly disease that acts
      swiftly to end life. Although it is the case that cancer mortality rates remain
      obstinately high in industrial countries, cancers are now seen as a chronic
      disease with uncertainty in remission, new recurrence, palliation, and death.
      Caregivers' commitment, emotional involvement, and understanding of the patients'
      needs demonstrate that caring is a special way of being, thinking and growing
      within the experience of the illness trajectory. Caring is fundamental to human
      survival. It is understood to imply a distinct way of being, believing, and
      acting that calls for commitment, knowledge, and new coping skills. It motivates
      families and gives meaning and structure to life. Informal family caregivers of
      cancer patients are required to meet multidimensional needs, including treatment
      monitoring; treatment-related symptom management; emotional, financial, and
      spiritual support; and assistance with personal and instrumental care. Families
      are increasingly replacing skilled healthcare workers in the delivery of
      unfamiliar complex care to their ill family members despite the other obligations
      and responsibilities that characterize their lives.

PMID- 21952566
TI  - Psychosocial challenges of elderly patients coping with cancer.
AB  - The objective of discussion is to stimulate healthcare professionals to deepen
      knowledge and understanding of the difficulties, challenges, and developmental
      tasks of elderly patients coping with cancer. Current research suggests that the
      psychological impact of cancer is less negative among the elderly, compared with
      younger patients (such as easier adjustment process). However, the specific
      psychosocial themes and needs of the elderly patients are not well enough
      adapted. Evidence-based data may offer clinicians and researchers a better
      understanding of the coping mechanisms defining elderly people, which may play a
      role in protecting them from severe emotional distress. Clinical implications
      would be improved screening, evaluation and intervention skills, which are
      suitable and adequate to the needs of the elderly population.

PMID- 21952567
TI  - Training oncology practitioners in communication skills.
AB  - Many practitioners in oncology receive no or little training in how to
      effectively communicate with patients and families who are dealing with cancer.
      Moreover medical teachers are not always aware of the pedagogy of teaching
      communication skills in a way that results in performance improvement in this
      area. In this paper a method of small group teaching that was used to instruct
      medical oncology fellows in the essentials of communication using a retreat
      format that lasted three days is described. The paper covers the theoretical
      basis for the teaching format as well as the specific components of the
      workshops. It describes the process of facilitation using a "learner-centered"
      approach using standardized patients who take on the role of cancer patients
      along the trajectory of the illness. It discuss the use of small group process to
      facilitate skills acquisition and other strategies that facilitate learning such
      as reflective exercises, open role play and parallel process. It concludes with a
      consideration of the various ways that such workshops can be evaluated.

PMID- 21952568
TI  - The importance of good communication between patient and health professionals.
AB  - This article emphasizes the importance of a good communication between patients
      and health professionals. It focuses on how patients feels during the cancer
      journey and how professionals should behave to them. It also go through the
      different dilemmas and conflicts health professionals may come across in their
      interaction with patients and it suggests different ways about how those dilemmas
      can be resolved. The main idea of this article is the fact that health
      professionals-whether physicians, nurses or psychologists-need to focus on and
      improve, if necessary, their communication with patients; basically, learn how to
      unite the humanistic side of care with the technical side; how to be
      professionals without losing their humanistic identity.

PMID- 21952569
TI  - The National Palliative Care Research Center and the Center to Advance Palliative
      Care: a partnership to improve care for persons with serious illness and their
      families.
AB  - The elimination of suffering and the cure of disease are the fundamental goals of
      medicine. While medical advances have transformed previously fatal conditions
      such as cancer and heart disease into illnesses that people can live with for
      many years, they have not been accompanied by corresponding improvements in the
      quality of life for these patients and their families. Living with a serious
      illness should not mean living in pain or experiencing symptoms like shortness of
      breath, nausea, or fatigue. Yet, multiple studies over the past decade suggest
      that medical care for patients with advanced illness is characterized by
      inadequately treated physical distress; fragmented care systems; poor
      communication between doctors, patients, and families; and enormous strains on
      family caregiver and support systems. Palliative care is interdisciplinary care
      focused on relief of pain and other symptoms and support for best possible
      quality of life for patients with serious illness, and their families. It is
      appropriate at the point of diagnosis of a serious illness. It goes beyond
      hospice care to offer patients and their families treatments focused on improving
      quality of life while they are receiving life-prolonging and curative treatments.
      Palliative care programs have been shown to reduce symptoms, improve doctor
      patient-family communication and satisfaction with care, as well as enhance the
      efficiency and effectiveness of hospital services. In the last 5 years alone the
      number of palliative care programs has more than doubled. This growth is in
      response to the increasing numbers and needs of Americans living with serious,
      complex and chronic illnesses, and the realities of the care responsibilities
      faced by their families. In order to ensure that all persons with serious illness
      and their families receive the quality of care they deserve, palliative care must
      become an integral part of the U.S. healthcare landscape. Specifically, persons
      facing serious illness and their families must know to request palliative care,
      medical professionals must have the knowledge and skills to provide palliative
      care, and hospitals and other healthcare institutions must be equipped to deliver
      and support palliative care services. The Center to Advance Palliative Care
      (CAPC) and the National Palliative Care Research Center (NPCRC) are accomplishing
      this three-part mission by working in partnership to: 1) Develop research to
      serve as the knowledge base for quality clinical care and the foundation on which
      to build palliative care programs and systems; 2) Disseminate this knowledge to
      patients, families, professionals, and institutions throughout the United States
      and ensure that it is integrated within mainstream healthcare; and 3) Influence
      and collaborate with policy makers , regulatory bodies, and federal funding
      agencies to ensure that the healthcare infrastructure supports the continued
      growth and development of palliative care.

PMID- 21952570
TI  - The barriers to and evidence for palliative care.
AB  - It is undeniable that there are barriers to providing palliative care. Recent
      research suggests there is value in palliative care for patients, families, and
      those providing this care. Specifically, the research suggests that the earlier a
      patient receives palliative care, the better outcomes they will receive. This
      article will serve 2 important purposes. First, this article will look at some of
      the barriers that sometimes prevent offering adequate palliative care to patient
      and families when the care is needed most. Second, this article will present
      results in a simplistic manner from actual research studies, which helps make the
      case through evidence of the value of palliative and quality end of life care.

PMID- 21952571
TI  - Ten best practices to enhance culturally competent communication in palliative
      care.
AB  - Communication involves a 2-way process of sending and receiving verbal and
      nonverbal messages. Communication is socially constructed and embedded in
      culture. This paper addresses the connection between communication and culture
      and provides several areas of importance to consider when assuring that
      individualized care is provided for persons with cancer and their families. Ten
      recommendations or best practices are suggested to enhance culturally competent
      communication in palliative care for adults with cancer.

PMID- 21952572
TI  - Measuring death-related anxiety in advanced cancer: preliminary psychometrics of
      the Death and Dying Distress Scale.
AB  - The alleviation of distress associated with death and dying is a central goal of
      palliative care, despite the lack of routine measurement of this outcome. In this
      study, we introduce the Death and Dying Distress Scale (DADDS), a new, brief
      measure we have developed to assess death-related anxiety in advanced cancer and
      other palliative populations. We describe its preliminary psychometrics based on
      a sample of 33 patients with advanced or metastatic cancer. The DADDS broadly
      captures distress about the loss of time and opportunity, the process of death
      and dying, and its impact on others. The initial version of the scale has a one
      factor structure and good internal reliability. Dying and death-related distress
      was positively associated with depression and negatively associated with
      spiritual, emotional, physical, and functional well-being, providing early
      evidence of construct validity. This distress was relatively common, with 45% of
      the sample scoring in the upper reaches of the scale, suggesting that the DADDS
      may be a relevant outcome for palliative intervention. We conclude by presenting
      a revised 15-item version of the scale for further study in advanced cancer and
      other palliative populations.

PMID- 21952573
TI  - Nurse's role in controlling cancer pain.
AB  - Nurses spend more time with patients than any other member of the healthcare
      team. They play a critical, active and very important part in controlling cancer
      patients' pain and alleviating suffering. In controlling cancer pain the nurse
      needs to understand the psychological state of the cancer patient, cancer pain,
      cancer pain treatment, deleterious effects of unrelieved cancer pain and
      patient's socio cultural background. She needs to understand that there are two
      types of pain, nociceptive and neuropathic pains and that 80% of the cancer
      patients in pain could have 2 or more than 4 different pains at the same time.
      Nurses' role in controlling cancer pain include believing the patient, assessing
      pain, identifying the root of the problem, planning the care, administering
      medication, evaluating effectiveness, ensuring good pain control and
      individualizing treatment. It also includes nursing interventions such as giving
      tender nursing care, preventing pain, educating, advocating, communicating,
      comforting, supporting, and counseling the patient. The nurse must use both
      pharmacological and non pharmacological treatments to individualize treatment,
      know all the drugs that are used for the treatment of Cancer Pain, how these
      drugs relieve pain and what their side effects are. She must use the WHO
      guidelines to treat pain and must choose the right drug, right dose, given at the
      right times, with the right intervals and to the right patient. She must evaluate
      effectiveness of treatment, give PRN doses for breakthrough pain and recommend
      for specific changes. The role of the nurse is to anticipate the patient's pain
      needs, advocate for the patient for what feels appropriate for him within his
      cultural context and incorporate the patient's belief. The nurse can physically
      relieve pain by promoting comfort, support painful area, gentleness in handling
      the patient and use nursing treatments. The nurse can recommend physiotherapy,
      (TENS)/Acupuncture, Occupational therapy, spiritual support, social worker,
      psychologist, and psychiatrist to address different types of pain. She must
      relieve both pain and other symptoms. and ensure that the patient has good sleep.
      She must show kindness, compassion and empathize with him. Each patient is unique
      the process of controlling cancer pain develops differently each time. The
      nurse's role is challenging, she must demonstrate that she is not only clinically
      proficient but culturally competent. She has to use creative assessment skills,
      clinical judgment, psychological support, advocacy and good communication skills
      in such a way that the contribution of drugs, nursing care, nursing and other non
      pharmacological treatments are maximized to the patient's benefit. When
      evaluating the overall care the nurse must find out what is the total effect of
      all approaches taken to relieve pain. Nurses can make a difference between a
      patient who suffers until the last breath of his/her life and a patient who is
      comfortable and dies pain free and in dignity.

PMID- 21952574
TI  - Unequal treatment in the US: lessons and recommendations for cancer care
      internationally.
AB  - Despite interventions that have improved the overall health of the majority of
      Americans, racial and ethnic minorities have benefited less from these advances.
      Research has shown that multiple factors contribute to racial and ethnic
      disparities in health, health care, and cancer care. The Institute of Medicine
      Report, "Unequal Treatment" provides a detailed examination of racial/ethnic
      disparities in health care in the U.S., highlighting three clinical contributors-
      poor provider-patient communication, stereotyping in clinical decisionmaking, and
      patient mistrust. Although the findings and recommendations in "Unequal
      Treatment" are broad in scope, they provide a blueprint for how to address
      disparities in health care in general-as well as cancer care-and have direct
      implications for clinical practice, both nationally and internationally. We
      propose a patient-based approach to cross-cultural care as a model to improve
      communication with racial and ethnic minorities, and cross-cultural populations
      in general. We also highlight the importance of community based interventions,
      such as those that use health care navigators to promote cancer screening. If we
      hope to provide effective cancer care around the world, we must be attentive to
      the factors that impact minorities and vulnerable populations, and be prepared to
      address them.

PMID- 21952575
TI  - Reality of pediatric cancer in Iraq.
AB  - This brief report displays comprehensive details of health services provided by
      Children's Welfare Teaching Hospital, medical city, Baghdad. In 2010; 366
      children with newly diagnosed cancer were admitted for treatment, two thirds were
      leukemia and lymphoma cases followed by other solid tumors except brain tumors.
      With this large number of patients; there are shortcomings in provision of health
      services in many aspects including professional manpower, infrastructure,
      diagnostic and therapeutic facilities, supportive and palliative care. The
      previous wars and sanction and the current instability of the country added to
      the socioeconomic difficulties of the families jeopardizing the appropriate
      therapy and ultimately the poor treatment outcome. Since 2003 an international
      collaboration had a major contribution in many aspects like provision of drugs
      and medical supplies, attendance of scientific workshops, and updating doctor's
      knowledge and experience through telemedicine programs which resulted in
      decreasing the induction mortality in acute lymphoblastic leukemia from 24% in
      the year 2007% to 10% in 2010 after introduction of pre-phase steroids and in
      acute promyelocytic leukemia from 95% to 5% after introduction of all trans
      retinoic acid. A collaborative work with Rome University resulted in changing
      diagnosis of 20% of pathological samples sent there for reevaluation. Iraqi
      pediatric oncologists still need real attempts to improve infrastructure and
      human resources in addition to twinning programs with internationally recognized
      cancer centers to face these management challenges.

PMID- 21952576
TI  - Development of palliative care in Israel and the rising status of the clinical
      nurse specialist.
AB  - It was in 2009 that the Ministry of Health in Israel issued unique recognition
      for registered nurses. Palliative Care has been recognized as a specialty for
      nurses, working already in different clinical specialties. By obtaining the
      qualification of a Clinical Nurse Specialist in Palliative Care, nurses obtained
      the de jure status of what they have been doing for years de facto.

PMID- 21952577
TI  - Perspective in supportive care--practical experiences in Georgia.
AB  - Authors describe the first steps of Palliative Care development in Georgia,
      including policy, educational issues, drug availability and services. It is
      underlined the importance and effectiveness of collaboration of Governmental
      institutions, NGOs and international organizations and experts to create the
      basis for Palliative care system in the Country. Georgian experience on revealing
      of problems of adequate pain control gained by survey with participation of
      advanced patients and their family members is also discussed. All current
      activities in the sphere of Palliative Care as well as the future models of
      Palliative Care provision in the capital and regions of Georgia is shown.

PMID- 21952578
TI  - Cultural perspectives in cancer care: impact of Islamic traditions and practices
      in Middle Eastern countries.
AB  - People's attitudes to cancer and its treatment are influenced by the patient's
      and his family's faith, beliefs, societal traditions, and cultural taboos and
      stigmatism. In most Middle Eastern countries Islam is the dominant religion, yet
      there are differences as to people's acceptance of cancer, starting with the
      realization of the diagnosis and the subsequent treatment planning. In many
      societies in the Middle East, patients prefer that their families will be the
      first to know about the disease and to agree to the planned treatment protocols.
      Whereas in Western societies the patient is usually the first to know,
      understand, and agree to the proposed therapeutic procedures; this is not the
      case in various Muslim societies. Health care professionals have to accept these
      kinds of practices and find ways to cope with their patients' sensitivities,
      thereby preserving their dignity and faith.

PMID- 21952579
TI  - Palliative care and the cancer patient:  current state and state of the art.
AB  - Comprehensive cancer care requires the integration of palliative care practices
      and principles across the trajectory of the cancer experience. It complements the
      treatment of curable disease and may be the sole focus of care for those patients
      with advanced incurable disease. As the incidence of cancer increases worldwide
      and the burden of cancer rises, especially in low and middle resource countries,
      the need for palliative care is greater than ever before. There are numerous
      barriers to the provision of integrated care, including the ongoing misconception
      that palliative care is end-of-life care, the "cure-care dichotomy," inadequate
      training of health professionals and lack of resources. This article reviews the
      essential elements of comprehensive cancer care and the challenges to providing
      integrated cancer and palliative care to patients world-wide.

PMID- 21952580
TI  - Impact of culture on health outcomes.
AB  - The diagnosis of cancer creates anticipatory grief and fear for the patient and
      the family, and the x cancer care experience is fraught with physical, emotional
      and spiritual challenges. The palliative care literature in Europe and North
      American is rapidly growing, but such literature is sparse in other parts of the
      world. Translating the findings from the West however, may be problematic in non
      Western, and particularly, non-Christian cultures, for many of the assumptions
      that underlie the approach to suffering and death in the West are culturally
      based in the values and beliefs of western European society. Therefore this paper
      provides a means to explore how such translation across cultures might occur by:
      (1) providing a definition of culture so that the context for the subsequent
      discussion is framed, (2) describing how culture impacts the cancer experience,
      (3) how culture affects communication to relieve suffering and improve quality of
      life for patients and families. The paper closes with 8 recommended steps to
      improve communication cross-culturally to provide effective quality palliative
      care for patients and families from diverse backgrounds.

PMID- 21952581
TI  - Cultural and spiritual considerations in palliative care.
AB  - Culture is a fundamental part of one's being. Spirituality is integrated with
      culture and both play a significant role in a person's journey through life. Yet,
      culture and spirituality are often misunderstood and may not seem to be important
      in healthcare settings. For adults with cancer and their families, this cannot be
      ignored. This paper reviews The Purnell Model of Cultural Competence as a
      framework for considering culture and spirituality in healthcare and discusses
      the importance of acknowledging and incorporating practices that support culture
      and spirituality in healthcare settings. Examples of how to include cultural and
      spiritual care in palliative and end-of-life care in healthcare settings are
      provided.

PMID- 21952582
TI  - Performance of a colorectal cancer screening protocol in an economically and
      medically underserved population.
AB  - The performance of combining fecal immunochemical tests (FITs) and a high-risk
      factor questionnaire (HRFQ) in colorectal cancer (CRC) screening in economically
      and medically underserved populations is uncertain. This study investigated the
      performance of a CRC screening protocol of combining FITs and an HRFQ as primary
      screening methods in a rural Chinese population. A CRC mass screening was
      conducted using FITs and an HRFQ as the first and colonoscopy as the second stage
      of screening in Jiashan, 2007-2009. The target population was 31,963 residents in
      three communities. The compliance was 84.7% for HRFQ, 76.4% for FITs, and 78.7%
      for colonoscopy. The detected rates of cancer, adenoma, nonadenomatous polyps,
      and advanced neoplasm were 2.7%, 14.8%, 5.9%, and 8.9% by FITs, which were higher
      than those by HRFQ (0.5%, 9.2%, 4.8%, and 3.8%, respectively). There was no
      significant difference in detected rate for nonadenomatous polyps between FITs
      and HRFQ. A total of 41.2% adenomas, 53.2% nonadenomatous polyps, and 29.8%
      advanced neoplasms were detected by HRFQ but missed by FITs. Positive predictive
      value of the screening protocol of combining FITs and HRFQ for advanced neoplasm
      was 5.7%, which was higher than FITs alone. Men had a higher prevalence of
      advanced neoplasm than women. Results indicate that combining FITs and HRFQ as
      primary screening methods is an efficient CRC screening strategy in economically
      and medically underserved populations.

PMID- 21952583
TI  - Revisit of field cancerization in squamous cell carcinoma of upper aerodigestive
      tract: better risk assessment with epigenetic markers.
AB  - We quantified field cancerization of squamous cell carcinoma in the upper
      aerodigestive tract with epigenetic markers and evaluated their performance for
      risk assessment. Methylation levels were analyzed by quantitative methylation
      specific PCR of biopsied specimens from a training set of 255 patients and a
      validation set of 224 patients. We also measured traditional risk factors based
      on demographics, lifestyle, serology, genetic polymorphisms, and endoscopy. The
      methylation levels of four markers increased stepwise, with the lowest levels in
      normal esophageal mucosae from healthy subjects without carcinogen exposure, then
      normal mucosae from healthy subjects with carcinogen exposure, then normal
      mucosae from cancer patients, and the highest levels were in cancerous mucosae (P
      < 0.05). Cumulative exposure to alcohol increased methylation of homeobox A9 in
      normal mucosae (P < 0.01). Drinkers had higher methylation of ubiquitin carboxyl
      terminal esterase L1 and metallothionein 1M (P < 0.05), and users of betel quid
      had higher methylation of homeobox A9 (P = 0.01). Smokers had increased
      methylation of all four markers (P < 0.05). Traditional risk factors allowed us
      to discriminate between patients with and without cancers with 74% sensitivity
      (95% CI: 67%-81%), 74% specificity (66%-82%), and 80% area under the curve (67%
      91%); epigenetic markers in normal esophageal mucosa had values of 74% (69%-79%),
      75% (67%-83%), and 83% (79%-87%); and both together had values of 82% (76%-88%),
      81% (74%-88%), and 91% (88%-94%). Epigenetic markers done well in the validation
      set with 80% area under the curve (73%-85%). We concluded that epigenetics could
      improve the accuracies of risk assessment.

PMID- 21952585
TI  - Possible role of visfatin in hepatoma progression and the effects of branched
      chain amino acids on visfatin-induced proliferation in human hepatoma cells.
AB  - Obesity and related metabolic abnormalities, including adipocytokine dysbalance,
      are risk factors for hepatocellular carcinoma (HCC). Visfatin, an adipocytokine
      that is highly expressed in visceral fat, is suggested to play a role in the
      progression of human malignancies. Branched-chain amino acids (BCAA) reduce the
      incidence of HCC in obese patients with liver cirrhosis and prevent obesity
      related liver carcinogenesis in mice. In this study, we investigated the possible
      role of visfatin on HCC progression and the effects of BCAA on visfatin-induced
      proliferation of HCC cells. In patients with HCCs, serum visfatin levels were
      significantly correlated with stage progression and tumor enlargement. Visfatin
      preferentially stimulated the proliferation of HepG2, Hep3B, and HuH7 human HCC
      cells compared with Hc normal hepatocytes. Visfatin phosphorylated extracellular
      signal-regulated kinase (ERK), Akt, and GSK-3beta proteins in HepG2 cells.
      LY294002 [a phosphoinositide-3-kinase (PI3K) inhibitor], PD98059 [a MAP/ERK 1
      kinase (MEK1) inhibitor], CHIR99021 (a GSK-3beta inhibitor), and BCAA
      significantly inhibited visfatin-induced proliferation in HepG2 cells. BCAA also
      inhibited phosphorylation of GSK-3beta, increased cellular levels of p21(CIP1),
      caused cell-cycle arrest in G(0)/G(1) phase, and induced apoptosis in HCC cells
      in the presence of visfatin. These findings suggest that visfatin plays a
      critical role in the proliferation of HCC cells and may be associated with the
      progression of this malignancy. In addition, BCAA might inhibit obesity-related
      liver carcinogenesis by targeting and, possibly, by overcoming the stimulatory
      effects of visfatin.

PMID- 21952584
TI  - Dietary energy balance modulates prostate cancer progression in Hi-Myc mice.
AB  - Male Hi-Myc mice were placed on three dietary regimens [30% calorie restriction
      (CR), overweight control (modified AIN76A with 10 kcal% fat), and a diet-induced
      obesity regimen (DIO) 60 kcal% fat]. All diet groups had approximately similar
      incidence of hyperplasia and low-grade prostatic intraepithelial neoplasia in the
      ventral prostate at 3 and 6 months of age. However, 30% CR significantly reduced
      the incidence of in situ adenocarcinomas at 3 months compared with the DIO group
      and at 6 months compared with both the overweight control and DIO groups.
      Furthermore, the DIO regimen significantly increased the incidence of
      adenocarcinoma with aggressive stromal invasion, as compared with the overweight
      control group (96% vs. 65%, respectively; P = 0.02) at the 6-month time point. In
      addition, at both 3 and 6 months, only in situ carcinomas were observed in mice
      maintained on the 30% CR diet. Relative to overweight control, DIO increased
      whereas 30% CR reduced activation of Akt, mTORC1, STAT3, and NFkappaB (p65) in
      ventral prostate. DIO also significantly increased (and 30% CR decreased) numbers
      of T-lymphocytes and macrophages in the ventral prostate compared with overweight
      control. The mRNA levels for interleukin (IL) 1alpha, IL1beta, IL6, IL7, IL23,
      IL27, NFkappaB1 (p50), TNFalpha, and VEGF family members were significantly
      increased in the ventral prostate of the DIO group compared with both the
      overweight control and 30% CR diet groups. Collectively, these findings suggest
      that enhanced growth factor (Akt/mTORC1 and STAT3) and inflammatory (NFkappaB and
      cytokines) signaling may play a role in dietary energy balance effects on
      prostate cancer progression in Hi-Myc mice.

PMID- 21952587
TI  - Toll-like receptor 1/2 stimulation induces elevated interleukin-8 secretion in
      polymorphonuclear leukocytes isolated from preterm and term newborn infants.
AB  - BACKGROUND: Neonatal neutrophil dysfunction contributes to inflammatory tissue
      damage in newborn infants. Toll-like receptors (TLRs) activate the innate immune
      response through recognition of pathogen-associated molecular patterns.
      Expression and function of TLRs by neonatal neutrophils has not well been
      characterized. OBJECTIVE: We hypothesized that, compared to polymorphonuclear
      leukocytes (PMNs) isolated from adults, neonatal PMNs isolated from either term
      or preterm infants express and release different levels of inflammatory cytokines
      and chemokines in response to stimulation with TLR1-9 agonists. METHODS: We
      stimulated PMNs isolated from preterm (n = 12) and term (n = 10) infants as well
      as adults (n = 10) with agonists recognized by TLRs1-9 and quantified chemokine
      and cytokine expression and secretion by ELISA and Luminex(r) multiplex
      quantification assay. RESULTS: Neonatal and adult PMNs stimulated with agonists
      recognized by TLRs1-9 differentially secrete inflammatory products. Signaling via
      TLR2 heterodimers is a potent mechanism for release of interleukin-8, a critical
      proinflammatory chemokine, by neonatal PMNs--a previously unrecognized facet of
      neonatal inflammation. Following TLR1/2 (PAM3CSK4) stimulation, interleukin-8
      secretion by neonatal PMNs, whether term or preterm, substantially exceeds that
      of adult PMNs assayed in parallel. CONCLUSIONS: These studies provide new
      insights relevant to the inflammatory biology of neonates, both term and preterm,
      and implicate exaggerated PMN recruitment in neonatal syndromes of dysregulated
      inflammation such as necrotizing enterocolitis or neonatal chronic lung disease.

PMID- 21952589
TI  - Study of the incorporation and release of the non-conventional half-sandwich
      ruthenium(II) metallodrug RAPTA-C on a robust MOF.
AB  - The highly porous and robust [Ni(8)(OH)(4)(OH(2))(2)(4,4'-(buta-1,3-diyne-1,4
      diyl)bispyrazolato)(6)](n) MOF can be used as a proof of concept for the
      incorporation and release of the non-conventional [Ru(p-cymene)Cl(2)(pta)] RAPTA
      C metallodrug.

PMID- 21952590
TI  - Simple routes to bulky silyl-substituted acetylide ligands and examples of
      V(III), Fe(II), and Mn(II) complexes.
AB  - Synthesis of substituted phenylacetylide ligands 2,6
      bis(trimethylsilyl)phenylacetylene (H1) and 2-(triphenylsilyl)phenylacteylene
      (H2) is reported. Ligand 1 supports tetrahedral complexes of V(III), Fe(II), and
      Mn(II) (3-5). Complexes 3-5 are high-spin and redox active.

PMID- 21952591
TI  - Instantaneous room-temperature and highly enantioselective ArTi(O-i-Pr)3
      additions to aldehydes.
AB  - Direct asymmetric additions of ArTi(O-i-Pr)(3) to aldehydes catalyzed by a
      titanium catalyst of (R)-H(8)-BINOL are reported. The reactions proceed
      instantaneously at room temperature, affording alcohols in >=90% ee. Importantly,
      the ArTi(O-i-Pr)(3) reagent differentiates the ligand effectiveness in an order
      of H(8)-BINOL > BINOL > TADDOL > diol 3 > disulfonamide 2.

PMID- 21952592
TI  - The use of non-invasive ventilation by Italian physicians in the clinical
      practice.

PMID- 21952593
TI  - Changes in heart rate variability across different degrees of acute dilutional
      anemia.
AB  - BACKGROUND: We investigated changes in heart rate variability (HRV) across
      different degrees of acute dilutional anemia (hemoglobin [Hb]=9, 7, 5, 4, and 3
      g/dL) in a pig model. METHODS: Twelve anesthetized mechanically ventilated pigs
      of either gender (mean body weight 27.5+/-5.5 kg) were hemodiluted by exchange of
      blood for hydroxyethyl starch (6%; 200000/0.5) from baseline values to each
      animal's individual critical hemoglobin concentration (Hbcrit 3.3 [2.3/3.6]
      g/dL). Differences in time- and frequency-domain calculations of HRV were
      analyzed throughout the hemodilution procedure by using short-term
      electrocardiogram recordings (analysis of variance+Dunn's post-hoc test).
      RESULTS: During the hemodilution procedure, the standard deviation of normal R-R
      intervals and the coefficient of variation changed at Hb 5.3 (4.2/5.7) g/dL.
      Thereafter, the high-frequency power (HF), total power of the variance, and root
      mean square of successive N-N interval differences changed at Hb 3.9 (3.1/4.3)
      g/dL. The low-frequency power (LF) and the LF/HF ratio remained unaffected by
      hemodilution to Hbcrit. CONCLUSION: Acute dilutional anemia resulted in
      significant changes in different time- and frequency-domain variables in HRV
      analysis. These changes occurred considerably earlier than did commonly
      recognized transfusion triggers or signs of general tissue hypoxia. Further
      investigation is warranted to elucidate whether these changes can be considered
      as indicators of imminent tissue hypoxia.

PMID- 21952594
TI  - Relationship between mixed venous oxygen saturation and regional cerebral
      oxygenation in awake, spontaneously breathing cardiac surgery patients.
AB  - BACKGROUND: In search of a non-invasive method for estimation of the oxygen
      balance this prospective study evaluates the relationship between regional
      cerebral oxygenation (rScO2) and mixed venous oxygen saturation in awake,
      spontaneously breathing patients after cardiac surgery. METHODS: After approval
      by the local ethical committee and written informed consent, 26 consecutive
      patients after cardiac surgery with cardiopulmonary bypass were enrolled. On
      intensive care unit (ICU), several hours after extubation, patients were
      connected to the INVOS 5100 cerebral monitor. Blood samples for determination of
      mixed venous oxygen saturation (SvO2) and central venous oxygen saturation
      (ScvO2) were drawn successively and rScO2 was documented. Patients were studied
      twice, breathing room air for the first measurement cycle, and breathing 4L/min
      supplemental oxygen by face mask, achieving a transcutaneous oxygen saturation
      above 98%, for a second measurement. RESULTS: Hemodynamic variables, hemoglobin
      and arterial carbon dioxide tension (PaCO2) remained stable between the two
      measurement cycles. Without oxygen, SvO2 and rScO2 showed a bias of -2.0%, limits
      of agreement (LOA) of -15.0 to 10.9% and a percentage error (PE) of 20.3%. SvO2
      and ScvO2 showed a bias of -3.9%, LOA of -13.9 to 6.2% and PE 15.7%. With oxygen,
      the bias between SvO2 and rScO2 was -2.5%, LOA -14.2 to 9.2%, PE 17.2%. Between
      SvO2 and ScvO2 the bias was -4.1%, LOA -10.2 to 2.1%, PE 9.0%. CONCLUSION: The
      rScO2 measured by near infrared spectroscopy was sufficiently representing mixed
      venous oxygen saturation in awake, hemodynamically stable, spontaneously
      breathing patients after cardiac surgery. The agreement was comparable to the
      agreement between SvO2 and ScvO2 with smaller differences in the lower ranges of
      SvO2.

PMID- 21952595
TI  - The nerve stimulation technique versus the loss of resistance technique for the
      posterior approach to lumbar plexus block: a randomized, prospective, observer
      blinded, pilot study.
AB  - BACKGROUND: This prospective, randomized, observer-blinded, pilot study compares
      the effects of the nerve stimulation guidance technique (NS) with the loss of
      resistance technique (LOR) on readiness for surgery during the posterior approach
      to lumbar plexus block. METHODS: Thirty ASA status I-III patients who were 18-85
      years old and who were undergoing hip fracture repair were enrolled. After
      parasacral sciatic nerve block, patients were randomly allocated to receive a
      continuous posterior lumbar plexus block using nerve stimulation (n=15) or a
      continuous psoas compartment block using the loss of resistance technique (n=15)
      with 20 ml of 1.5% mepivacaine. A blinded observer monitored for sensory and
      motor block onsets every 5 minutes. We defined readiness for surgery as complete
      numbness to the pinprick test and complete motor block on the surgical side. If
      incomplete, the lumbar plexus block was supplemented with 10 mL of 1.5%
      mepivacaine through the catheter before surgery. Intraoperative fentanyl or
      general anesthesia requirements, pain scores, local anesthetic consumption,
      morphine requirements for breakthrough pain and side effects were monitored.
      RESULTS: The mean time to readiness for surgery was 12+/-6 min Group NS and 22+/
      6 min in Group LOR (P=0.03). Three patients in Group NS and 9 patients in Group
      LOR required additional boluses of local anesthetic through the lumbar plexus
      catheter before surgery (P=0.113). CONCLUSION: Nerve stimulation allowed faster
      readiness for surgery than loss of resistance. Nevertheless, the two techniques
      seem to be comparable in terms of local anesthetic consumption, morphine
      requirements and pain scores.

PMID- 21952596
TI  - Superinfections in Pseudomonas aeruginosa ventilator-associated pneumonia.
AB  - BACKGROUND: Data on superinfections in patients with ventilator-associated
      pneumonia vary, but different pathogens are typically studied as a single
      category. We studied the incidence of superinfections and the outcomes of
      patients with superinfections in Pseudomonas aeruginosa ventilator-associated
      pneumonia. METHODS: Sixty patients with Pseudomonas aeruginosa ventilator
      associated pneumonia were initially treated appropriately. On day three of follow
      up, bronchoalveolar lavage was collected. For Pseudomonas aeruginosa species that
      reached >104 colony forming units/ml upon follow-up, bronchoalveolar lavage
      pulsed gel field electrophoresis was applied. Accordingly, Pseudomonas aeruginosa
      was identified as a superinfection when isolates were genetically unrelated to
      those isolated at study entry or as a persistence of infection when isolates were
      closely related. RESULTS: Upon follow-up, 15 (25%) patients displayed
      superinfections with Pseudomonas aeruginosa that was resistant to the initial
      antibiotic regimen. Forty-five (75%) patients did not have a superinfection upon
      follow-up. Among these patients, 18 (30%) had a persistent infection , as
      determined by the significant counts of initial Pseudomonas aeruginosa isolates
      that had developed resistance, and 27 (45%) had persistence in which
      insignificant counts of initial Pseudomonas aeruginosa isolates remained
      sensitive to the initial antibiotics. Antibiotic treatment was adjusted for
      patients with superinfections and persistence with the development of resistance.
      The Simplified Acute Physiology Score (45.1+/-4.9 versus 43+/-4.9, P=0.38), the
      Sequential Organ Failure Assessment (4.13+/-2.5 versus 4.7+/-2.7, P=0.53) and
      mortality (20% versus 17.7%, P~1.00) were comparable on day-14 for patients with
      and without a superinfection. CONCLUSION: For Pseudomonas aeruginosa ventilator
      associated pneumonia, superinfections are not uncommon as early as day three, but
      they do not increase mortality.

PMID- 21952597
TI  - Survey of non-invasive ventilation practices: a snapshot of Italian practice.
AB  - BACKGROUND: In Italy, NIV began to be employed in the late 1980s. Because it was
      adopted earlier than in Italy than in other countries, the pattern and rate of
      utilization of NIV may be different. We aim to determine factors that may
      influence Italian physicians' preferences towards NIV use, with a particular
      emphasis on the primary specialty of these physicians and the type of hospital in
      which they work. METHODS: We re-examined the data from our European survey
      conducted in 2008 and focused our analysis on the Italian subsets of respondents
      to explore factors that influence physicians' perceptions of their NIV practices
      in four scenarios: acute hypercapnic respiratory failure (AHRF), cardiogenic
      pulmonary edema (CPE), de novo respiratory failure, and weaning/post-extubation
      failure (W/PE). RESULTS: On average, NIV was equally applied in university and
      community hospitals (P>0.05) and its utilization rate was higher for
      pulmonologists (62% reported >20% of patients treated with NIV a year) vs.
      intensivists (17%) and others (21%) (P<0.05). A greater use of NIV was related to
      a smaller number of unit beds in de novo respiratory failure (56% vs. 40%) and a
      larger amount of unit beds in AHRF (16% vs. 7%) (P<0.05). Dedicated NIV platforms
      and ICU ventilators with NIV modules were the preferred machines in AHRF
      (P<0.05), while a greater utilization of ICU ventilators with NIV modules was
      observed in de novo respiratory failure. In all the scenarios, a facial mask was
      predominantly used (P<0.05), with the helmet rated as the second preferred choice
      in CPE. CONCLUSION: Overall, Italian physicians perceived that NIV represents an
      essential tool when dealing with acute episodes of respiratory failure,
      irrespective of the type of hospital in which they worked.

PMID- 21952598
TI  - Reliability of the HemoCue(r) hemoglobinometer in critically ill patients: a
      prospective observational study.
AB  - BACKGROUND: The aim of the study was to assess the reliability of hemoglobin
      measurements made with HemoCue(r), compared with those made with the reference
      method in critically ill patients. METHODS: A prospective observational study was
      conducted in three adult surgical intensive care units of a university hospital.
      One hundred and ninety-eight consecutive patients were included, and a total of
      1166 hemoglobin concentrations were measured using arterial blood samples in the
      laboratory (HbLAB) and at bedside (HbHC.art) with a portable hemoglobinometer
      (HemoCue(r) Hb201+). Simultaneously, a capillary measurement (HbHC.cap) was
      performed at bedside using the same device. RESULTS: The mean difference (bias)
      between HbHC.cap and HbLAB was 0.2 g/dL (95%CI, 0.1;0.3), and limits of agreement
      were -1.3 g/dL (95%CI, -1.4;-1.2) to 1.7 g/dL (95%CI, 1.6;1.9). The discrepancies
      between HbHC.cap and HbLAB were greater than 1 g/dL in 30.8% of cases. The bias
      between HbHC.art and HbLAB was -0.1 g/dL (95% CI, -0.2;0.2), and limits of
      agreement were slightly better at -1.1 g/dL (95% CI, -1.2;-1.0) and 1.0 g/dL (95%
      CI, 0.9;1.1). The HemoCue(r)'s accuracy was not affected by the hospital unit,
      the puncture site (finger or ear), norepinephrine administration or by hemoglobin
      levels below 10 g/dL or 8 g/dL. CONCLUSION: Capillary HemoCue(r) is not
      sufficiently accurate to make a therapeutic decision such as whether a blood
      transfusion should be performed. The method's performance was moderately improved
      by the use of arterial blood.

PMID- 21952599
TI  - Differences between adult and pediatric septic shock.
AB  - Sepsis is a significant public health problem that affects children and adults
      alike. Despite some similarities in the approach to pediatric and adult septic
      shock, there are key differences as it relates to pathophysiology, clinical
      presentation, and therapeutic approaches. In this review article, we discuss
      these differences under 4 headings: a) Developmental differences in the
      hemodynamic response, b) Activated Protein C, c) Thrombocytopenia associated
      multiple organ failure and d) Hemophagocytic Lymphohistiocytosis (HLH).

PMID- 21952600
TI  - Advances in resuscitative trauma care.
AB  - Over the last two decades, experimental and clinical data have begun to shape a
      more discriminating approach to intravascular (IV) fluid infusions in the
      resuscitation of trauma patients with presumed internal hemorrhage. This approach
      takes into account the presence of potentially uncontrollable hemorrhage (e.g.,
      deep intra-abdominal or intra-thoracic injury) versus a controllable source (e.g.
      distal extremity wound). This limitation on fluid resuscitation is particularly
      applicable in the case of patients with penetrating truncal injury being
      transported rapidly to a nearby definitive care center. Meanwhile, longstanding
      debates over the type of fluid that should be infused remain largely unresolved
      and further complicated by recent clinical trials that did not demonstrate
      support for either hemoglobin-based oxygen carriers or hypertonic saline.
      However, there is also growing evidence that does support the increased use of
      fresh frozen plasma as well as tourniquets, and intra-osseous devices. While a
      more discriminating approach to fluid infusions have evolved, it has also become
      clear that positive pressure ventilatory support should be limited in the face of
      potential severe hemorrhage due to the accompanying reductions in venous return.
      Controversies over prehospital endotracheal tube placement are confounded by this
      factor as well as the effects of paramedic deployment strategies and related
      skills usage. Beyond these traditional areas of focus, a number of very
      compelling clinical observations and an extensive body of experimental data has
      generated a very persuasive argument that intravenous estrogen and progesterone
      may be of value in trauma management, particularly severe traumatic brain injury
      and burns.

PMID- 21952601
TI  - Italian intersociety consensus statement on antithrombotic prophylaxis in hip and
      knee replacement and in femoral neck fracture surgery.
AB  - Anticoagulant prophylaxis for preventing venous thrombembolism (VTE) is a
      worldwide established procedure in hip (HR) and knee replacement (KR) surgery, as
      well as in the treatment of femoral neck fractures (FNF). Different guidelines
      are available in the literature, with quite different recommendations. None of
      them is a multidisciplinary effort as the one presented. The Italian Society for
      Studies on Hemostasis and Thrombosis, the Italian Society of Orthopedics and
      Traumatology, the association of Orthopedic Traumatology of Italian Hospitals,
      together with the Italian Society of Anesthesia, Analgesia, Resuscitation, and
      Intensive Care have set down easy and quick suggestions for VTE prophylaxis in HR
      and KR surgery as well as in FNF treatment. This inter-society consensus
      statement aims at simplifying the grading system reported in the literature, and
      thus at improving its proper application. Special focus is given to fragile
      patients, those with high bleeding risk, and on those receiving chronic
      antiplatelet and vitamin K antagonists treatment. A special chapter is dedicated
      to regional anesthesia and VTE prophylaxis.

PMID- 21952602
TI  - Can we easily anticipate on admission pediatric patient transfers from
      intermediate to intensive care?

PMID- 21952603
TI  - Should we revise out-of-hospital rewarming following successful CPR in pediatric
      drowning victims?

PMID- 21952604
TI  - Apoptosis in skeletal myocytes: a potential target for interventions against
      sarcopenia and physical frailty - a mini-review.
AB  - BACKGROUND: Sarcopenia, the age-related loss of muscle mass and function,
      represents a relevant public health issue due to its high prevalence and
      detrimental consequences. While the exact mechanisms underlying the pathogenesis
      of sarcopenia are not clear, growing experimental evidence indicates that
      progressive myonuclear elimination over the course of aging via an apoptosis-like
      process may represent a converging mechanism through which muscle atrophy and
      loss of physical function develop. Notably, the proapoptotic environment taking
      place in aged muscle appears amenable to interventions. OBJECTIVE: We aimed at
      providing (1) an overview of signaling pathways of apoptosis relevant to
      sarcopenia, and (2) a review of the literature supporting myocyte apoptosis as a
      target for interventions against muscle aging. METHODS: We summarized findings
      from studies focused on skeletal myocyte apoptosis as a mechanism in the
      development of sarcopenia and reports supporting myonuclear apoptosis as a target
      for interventions against age-related muscle loss. RESULTS: Advanced age is
      associated with increased signaling through extrinsic and intrinsic apoptotic
      pathways in skeletal myocytes. In contrast, downregulation of myocyte apoptosis
      through calorie restriction, exercise training, hormonal supplementation, drugs
      (e.g. angiotensin-converting enzyme inhibitors, acetaminophen, antimyostatin
      antibodies), nutraceuticals or genetic interventions (e.g. PGC-1alpha
      overexpression) is linked with preservation of muscle integrity and improved
      physical performance in late life. Preliminary data also indicate that skeletal
      myocyte apoptotic signaling may be downregulated by compounds, such as
      resveratrol, with calorie restriction-mimicking properties. Whether exercise
      mimetics exert a similar effect has not yet been investigated. CONCLUSIONS:
      Available evidence suggests that targeting myonuclear apoptosis might provide
      novel and effective therapeutic tools to combat sarcopenia. Further research is
      required to definitely establish if downregulating myonuclear apoptosis is
      effective in maintaining muscle mass and function in late life, identify the most
      relevant apoptotic pathway(s) to target, and determine the optimal timing for
      intervening.

PMID- 21952605
TI  - A novel approach to the study of hypoxia-ischemia-induced clinical and
      subclinical seizures in the neonatal rat.
AB  - Perinatal hypoxic-ischemic encephalopathy (HIE) is a major cause of acute
      mortality and chronic neurologic morbidity in infants and children. HIE is the
      most common cause of neonatal seizures, and seizure activity in neonates can be
      clinical, with both EEG and behavioral symptoms, subclinical with only EEG
      activity, or just behavioral. The accurate detection of these different seizure
      manifestations and the extent to which they differ in their effects on the
      neonatal brain continues to be a concern in neonatal medicine. Most experimental
      studies of the interaction between hypoxia-ischemia (HI) and seizures have
      utilized a chemical induction of seizures, which may be less clinically relevant.
      Here, we expanded our model of unilateral cerebral HI in the immature rat to
      include video EEG and electromyographic recording before, during and after HI in
      term-equivalent postnatal-day-12 rats. We observed that immature rats display
      both clinical and subclinical seizures during the period of HI, and that the
      total number of seizures and time to first seizure correlate with the extent of
      tissue damage. We also tested the feasibility of developing an automated seizure
      detection algorithm for the unbiased detection and characterization of the
      different types of seizure activity observed in this model.

PMID- 21952606
TI  - Reactivity of acyclic (pentadienyl)iron(1+) cations: synthetic studies directed
      toward the frondosins.
AB  - A short, 4-step route to the scaffold of frondosin A and B is reported. The [1
      methoxycarbonyl-5-(2',5'-dimethoxyphenyl)pentadienyl]Fe(CO)(3)(+) cation was
      prepared in two steps from (methyl 6-oxo-2,4-hexadienoate)Fe(CO)(3). Reaction of
      this cation with isopropenyl Grignard or cyclohexenyllithium reagents affords (2
      alkenyl-5-aryl-1-methoxycarbonyl-3-pentene-1,5-diyl)Fe(CO)(3) along with other
      addition products. Oxidative decomplexation of these (pentenediyl)iron complexes,
      utilizing CuCl(2), affords 6-aryl-3-methoxycarbonyl-1,4-cycloheptadienes via the
      presumed intermediacy of a cis-divinylcyclopropane.

PMID- 21952607
TI  - Hypocomplementemic urticarial vasculitis syndrome: a rare cause of basilar
      panacinar emphysema.
AB  - Hypocomplementemic urticarial vasculitis syndrome (HUVS) is a rare condition
      characterized by an immune complex-mediated disruption of multiple organ systems.
      Pulmonary involvement is a major cause of morbidity and mortality in patients
      with HUVS. HUVS has been described by clinical, histological, and laboratory
      findings. However, the role of radiography in the diagnosis and management of
      HUVS has not been established. We examine computed tomography findings in a
      patient with HUVS and explore the potential of thoracic computed tomography
      imaging to augment the management of HUVS by serving as a diagnostic tool and
      marker of disease severity.

PMID- 21952608
TI  - Exogenous lipoid pneumonia induced by aspiration of insecticide.
AB  - Exogenous lipoid pneumonia is a rare disorder caused by inhalation and/or
      aspiration of oil-based substances. The confirmed diagnosis of exogenous lipoid
      pneumonia is difficult, especially in cases for which it is impossible to
      ascertain a history of inhalation or aspiration. We present a case of exogenous
      lipoid pneumonia due to aspiration of insecticide, for which the computed
      tomography findings of fat attenuation within the lesion were helpful in reaching
      a correct diagnosis.

PMID- 21952609
TI  - Evaluation of perivalvular infectious ventricular pseudoaneurysm by ECG-gated
      cardiac computed tomography: 2 case reports.
AB  - Left ventricular (LV) pseudoaneurysm is a serious complication of periannular
      extension of infective endocarditis (IE). Because pseudoaneurysm carries a high
      risk of rupture, its detection and evaluation are crucial for patient management
      and surgical planning. We report 2 cases with LV pseudoaneurysms, one near the
      aortic valve and the other near the mitral valve, which were caused by IE and
      treated successfully. In both cases, cardiac multidetector-row computed
      tomography enabled detection of the LV pseudoaneurysm and a detailed
      demonstration of its anatomic relationship with surrounding structures, which
      helped guide surgical planning.

PMID- 21952610
TI  - An extended bioreaction database that significantly improves reconstruction and
      analysis of genome-scale metabolic networks.
AB  - The bioreaction database established by Ma and Zeng (Bioinformatics, 2003, 19,
      270-277) for in silico reconstruction of genome-scale metabolic networks has been
      widely used. Based on more recent information in the reference databases KEGG
      LIGAND and Brenda, we upgrade the bioreaction database in this work by almost
      doubling the number of reactions from 3565 to 6851. Over 70% of the reactions
      have been manually updated/revised in terms of reversibility, reactant pairs,
      currency metabolites and error correction. For the first time, 41 spontaneous
      sugar mutarotation reactions are introduced into the biochemical database. The
      upgrade significantly improves the reconstruction of genome scale metabolic
      networks. Many gaps or missing biochemical links can be recovered, as exemplified
      with three model organisms Homo sapiens, Aspergillus niger, and Escherichia coli.
      The topological parameters of the constructed networks were also largely
      affected, however, the overall network structure remains scale-free. Furthermore,
      we consider the problem of computing biologically feasible shortest paths in
      reconstructed metabolic networks. We show that these paths are hard to compute
      and present solutions to find such paths in networks of small and medium size.

PMID- 21952611
TI  - Usefulness of a slow nutrient drinking test for evaluating gastric perception and
      accommodation.
AB  - BACKGROUND/AIM: An implication of the drinking test for gastric function is
      controversial. We evaluated the usefulness of a nutrient drinking test for
      examining gastric function by comparing it with a gastric barostat study.
      METHODS: We investigated perceived pressure of an intragastric bag with stepwise
      distension and postprandial peak gastric volume (accommodation volume) with a
      consistent pressure after drinking a liquid meal (200 ml, 300 kcal) in 18
      volunteers. Drinking a similar liquid meal on a different day at a continual rate
      of 15 ml/min was performed to score satiety and bloated sensations at 5-min
      intervals. An additional 10 volunteers performed the drinking test before and
      after administration of mosapride citrate or a placebo in a double-blind
      crossover study. RESULTS: Pressure to induce severe discomfort correlated
      positively with maximum satiety volume in the drinking test (r = 0.60, p = 0.02).
      Accommodation volume in the barostat study showed a significant correlation (r =
      0.59, p = 0.03) with threshold volume to induce bloating in the drinking test.
      Mosapride tended to increase the volume inducing the first bloated sensation as
      compared to the placebo. CONCLUSION: The present drinking test may be useful for
      evaluating the threshold to induce severe discomfort and accommodation volume.

PMID- 21952612
TI  - Sedimentation velocity of intrinsically disordered proteins: what information can
      we actually obtain?
AB  - Intrinsically disordered proteins are a challenge to characterise structurally
      because of their innate flexibility. Hydrodynamic methods such as sedimentation
      velocity analytical ultracentrifugation have been proposed as methods for their
      characterisation. By examining in detail this assumption we show that although
      velocity measurements do yield information on gross conformation, the information
      is restricted to only the weight averaged sedimentation and diffusion
      coefficients of the conformational ensemble.

PMID- 21952613
TI  - Titanium wire-based SPE coupled with HPLC for the analysis of PAHs in water
      samples.
AB  - Titanium wire-based solid phase extraction (SPE) is developed for the analysis of
      six different polycyclic aromatic hydrocarbons in water samples with coupling
      with high performance liquid chromatography. The adsorbent is a Ti wire on which
      TiO(2) nanotubes are first formed by anodization and then Au nanoparticles and n
      octadecanethiol are modified. The surface composition and structure of the
      adsorbent were characterized in detail using field emission scanning electron
      microscope and Fourier transform infrared spectroscopy. The main parameters
      affecting the extraction efficiency, such as the volume of the organic modifier,
      extraction time, elution solvent, and desorption time were optimized. Good
      linearities ranging from 0.025 to 30 MUg L(-1) with correlation coefficients
      (R(2)) ranging from 0.9964 to 0.9999 and low limits of detection were obtained in
      spiked water samples. Furthermore, this method was successfully applied in the
      analysis of real river water samples with recoveries in the range of 75.33
      115.83% and relative standard deviations ranging from 4.85 to 10.77%. The
      developed SPE can be a particularly convenient means of sample pretreatment for
      environmental water samples.

PMID- 21952615
TI  - Impaired diastolic function and disruption of the force-frequency relationship in
      the right ventricle of newborn pigs resuscitated with 100% oxygen.
AB  - BACKGROUND: Resuscitation with 100% oxygen increases oxidative stress and is
      detrimental for organ function. OBJECTIVE: To study the effects of resuscitation
      with 100% oxygen compared to room-air on myocardial function. METHODS: Twenty
      eight newborn pigs underwent global hypoxia (8% oxygen/N2) until base excess
      reached -20 mmol/l. The animals were randomized into two groups and resuscitated
      with either 100% or room air for 30 min. Myocardial tissue Doppler velocities and
      acceleration of the mitral and tricuspid valve annuli during systole and diastole
      were assessed before global hypoxia and after resuscitation together with
      troponin I. RESULTS: Peak early diastolic velocity (E') and acceleration (pEac)
      in the septum and pEac in the lateral tricuspid valve annulus were lower after
      resuscitation with 100% oxygen, suggesting impaired diastolic relaxation in the
      right ventricle. Lower systolic velocities and acceleration in the right
      ventricle relative to heart rate indicate disruption of the right ventricular
      force-frequency relationship after resuscitation with 100% oxygen. Troponins were
      higher in the 100% oxygen group, suggesting increased myocardial damage in this
      group. CONCLUSION: Resuscitation with 100% oxygen compared to room air induces
      diastolic dysfunction, disrupts the systolic force-frequency relationship and
      increases myocardial damage in the newborn pig.

PMID- 21952617
TI  - Competitive binding of small molecules with biopolymers: a fluorescence
      spectroscopy and chemometrics study of the interaction of aspirin and ibuprofen
      with BSA.
AB  - The interaction of aspirin and ibuprofen with bovine serum albumin (BSA) was
      studied by spectrofluorimetry under simulated physiological conditions. Both
      aspirin and ibuprofen quenched the intrinsic fluorescence of BSA and the binding
      ratios obtained were 2 : 1 for aspirin-BSA and 3 : 1 for ibuprofen-BSA
      interactions, respectively. The thermodynamic parameters (DeltaH, DeltaS and
      DeltaG) obtained from the fluorescence spectroscopy data showed that the binding
      of aspirin to BSA involved van der Waals interactions and hydrogen bonds.
      Competitive experiments using warfarin and diazepam as site markers indicated
      that aspirin was mainly located in the hydrophobic pocket of site II of the
      protein as well as to a small extent in site I. Furthermore, the competitive
      interaction of the aspirin and ibuprofen with BSA, which was studied with the use
      of the three-way excitation-emission fluorescence spectra and a parallel factor
      analysis (PARAFAC) chemometrics method, showed that the competitive effect of
      ibuprofen was stronger than that of aspirin, i.e. the former molecule replaced
      the aspirin from the aspirin-BSA complex.

PMID- 21952618
TI  - Characterization of 4,4'-biphenylene-silicas and a chiral sensor for silicas.
AB  - The CD spectra of chiral 4,4'-biphenylene-silicas were measured and simulated
      using time-dependent density functional theory and a chiral sensor for silicas
      was developed.

PMID- 21952616
TI  - Focal adhesion kinase regulates neuronal growth, synaptic plasticity and
      hippocampus-dependent spatial learning and memory.
AB  - The focal adhesion kinase (FAK) is a non-receptor tyrosine kinase abundantly
      expressed in the mammalian brain and highly enriched in neuronal growth cones.
      Inhibitory and facilitatory activities of FAK on neuronal growth have been
      reported and its role in neuritic outgrowth remains controversial. Unlike other
      tyrosine kinases, such as the neurotrophin receptors regulating neuronal growth
      and plasticity, the relevance of FAK for learning and memory in vivo has not been
      clearly defined yet. A comprehensive study aimed at determining the role of FAK
      in neuronal growth, neurotransmitter release and synaptic plasticity in
      hippocampal neurons and in hippocampus-dependent learning and memory was
      therefore undertaken using the mouse model. Gain- and loss-of-function
      experiments indicated that FAK is a critical regulator of hippocampal cell
      morphology. FAK mediated neurotrophin-induced neuritic outgrowth and FAK
      inhibition affected both miniature excitatory postsynaptic potentials and
      activity-dependent hippocampal long-term potentiation prompting us to explore the
      possible role of FAK in spatial learning and memory in vivo. Our data indicate
      that FAK has a growth-promoting effect, is importantly involved in the regulation
      of the synaptic function and mediates in vivo hippocampus-dependent spatial
      learning and memory.

PMID- 21952619
TI  - Percutaneous management of ureteral stenosis of transplanted kidney: technical
      and clinical aspects.
AB  - In the field of renal transplantation, advances in the management of graft
      rejection have led to improved graft and patient survival rates, however other
      types of complications have now become more apparent, e.g. vascular or
      urological. The most common urological complications following renal
      transplantation are ureteral stenosis or obstruction, constituting a significant
      problem of the renal graft's survival. The most important aspects concerning
      these complications are early diagnosis and prompt treatment since any delay in
      their management may lead to renal graft dysfunction or even graft loss.
      Developments in interventional radiology have provided minimally invasive means
      to treat urological complications with low complication rates. Herein we review
      the literature in order to evaluate the efficacy of percutaneous management of
      ureteral stenosis regarding its safety, immediate and long-term results,
      complications as well as rate of recurrence.

PMID- 21952620
TI  - The influence of cyclodextrin modification on cellular uptake and transfection
      efficiency of polyplexes.
AB  - Cyclodextrin-modified polycations have been studied widely due to their low
      cytotoxicity, low immunogenicity and the ability to form inclusion complexes.
      However, the influence of CD modification on cellular uptake and transfection
      efficiency of polyplexes is still unclear. In this research, cyclodextrin
      modified polyethylenimines (PEI-CD) with different CD-grafting levels were
      synthesized, which were named PEI-CD(15) and PEI-CD(41), respectively, according
      to the CD number per PEI chain. CD modification showed great influence on the DNA
      condensation ability of the polycation. PEI-CD(15) could protect DNA completely
      above N/P ratio of 2. The particle sizes of these polyplexes were about 120 nm.
      However, PEI-CD(41) could not protect DNA below N/P of 6, and PEI-CD(41)/DNA
      polyplexes were larger than 1 MUm, even at N/P ratio of 10. Therefore, this
      research was mainly focused on PEI-CD(15). It was interesting that the PEI
      CD(15)/DNA polyplexes at N/P ratio of 8 and 10 displayed excellent stability in
      physiological salt conditions, probably due to the hydration shell of CDs. The
      influence of CD modification on the cellular uptake and transfection efficiency
      of polyplexes depended on the type of the cells. Uptake inhibition experiments
      indicated that PEI/DNA polyplexes were internalized by HEK293T cells by both
      clathrin-mediated endocytosis and caveolae-mediated endocytosis. The route of
      caveolae-mediated endocytosis was significantly promoted after CD modification.
      So the cell uptake and transfection efficiency of PEI-CD(15)/DNA polyplexes were
      significantly improved for HEK293T cells. However, the uptake and transfection
      efficiency of PEI-CD(15)/DNA polyplexes in HepG2 cells was similar to that of
      PEI/DNA polyplexes, probably due to the lack of endogenous caveolins.

PMID- 21952621
TI  - Upregulated FGFR1 expression is associated with the transition of hormone-naive
      to castrate-resistant prostate cancer.
AB  - BACKGROUND: Prostate cancer (PC) represents a global health issue. Treatment for
      locally advanced and metastatic PC remains unsatisfactory. The androgen receptor
      (AR) has been validated in having a key role in both naive and castrate-resistant
      PC (CRPC). However, the significance of other signalling pathways in CRPC is less
      well validated. METHODS: To gain a better insight into the molecular signalling
      cascades involved in clinical CRPC, we performed gene expression profiling using
      the Illumina DASL assay and studied matched hormone-naive (HN) and CR prostate
      tumours (n=10 pairs). Ingenuity Pathways Analysis (IPA) was used to identify
      potential networks involved, and further validation was performed in in vitro
      cell models and clinical tumours. RESULTS: Expression of 50 genes was
      significantly different between HN and CRPC. IPA revealed two networks of
      particular interest, including AR and FGFR1, respectively. FGFR1 expression was
      confirmed to be significantly upregulated in CRPC (P <= 0.005), and abnormal
      FGFR1 expression was associated with shorter time to biochemical relapse in HNPC
      (P=0.006) and less favourable disease-specific survival in CRPC (P=0.018).
      CONCLUSION: For the first time, our gene expression profiling experiment on
      archival tumour materials has identified upregulated FGFR1 expression to be
      associated with PC progression to the CR state.

PMID- 21952622
TI  - BRCA2 is a moderate penetrance gene contributing to young-onset prostate cancer:
      implications for genetic testing in prostate cancer patients.
AB  - BACKGROUND: A family history of prostate cancer (PrCa) is a strong risk factor
      for the disease, indicating that inherited factors are important in this disease.
      We previously estimated that about 2% of PrCa cases diagnosed <= 55 years harbour
      a BRCA2 mutation and PrCa among BRCA2 carriers has been shown to be more
      aggressive, with poorer survival. METHODS: To further evaluate the role of BRCA2
      in PrCa predisposition, we screened 1864 men with PrCa aged between 36 and 88
      years. We analysed the BRCA2 gene using a novel high-throughput multiplex
      fluorescence heteroduplex detection system developed for the ABI3130xl genetic
      analyzer. RESULTS: We identified 19 protein-truncating mutations, 3 in-frame
      deletions and 69 missense variants of uncertain significance (UV) in our sample
      set. All the carriers of truncating mutations developed PrCa at <= 65 years, with
      a prevalence of BRCA2 mutation of 1.20% for cases in this age group. CONCLUSION:
      Based on the estimated frequency of BRCA2 mutations in the United Kingdom we
      estimate that germline mutations in the BRCA2 gene confer an ~ 8.6-fold increased
      risk of PrCa by age 65, corresponding to an absolute risk of ~ 15% by age 65.
      These results suggest that routine testing of early onset PrCa cases for germline
      BRCA2 mutations will further help to refine the prevalence and risk associated
      with BRCA2 mutations and may be useful for guiding management options.

PMID- 21952623
TI  - Adenoviruses-mediated transduction of human oesophageal carcinoma cells with the
      interferon-lambda genes produced anti-tumour effects.
AB  - BACKGROUND: Interferon-lambdas (IFN-lambdas) are novel cytokines with multiple
      functions, like IFN-alpha and -beta. We examined possible anti-tumour effects
      produced by adenoviruses bearing the IFN-lambda1 or -lambda2 gene (Ad/IFN-lambda)
      with the type-35 fibre-knob structure. METHODS: Proliferation of oesophageal
      carcinoma cells transduced with Ad/IFN-lambda and mechanisms of the inhibited
      growth were investigated. RESULTS: Transduction with Ad/IFN-lambda upregulated
      the expression of the class I antigens of the major histocompatibility complexes
      and induced the growth suppression. Increased sub-G1 populations and the cleavage
      of caspase-3 and poly (ADP-ribose) polymerase were detected in IFN-lambda
      sensitive YES-2 and T.Tn cells. The cell death was accompanied by cytoplasmic
      cytochrome C and increased cleaved caspase-9 and Bax expression, suggesting
      mitochondria-mediated apoptosis. Adenovirus/IFN-lambda-infected YES-2 cells
      subsequently reduced the tumourigenicity. Adenovirus/IFN-lambda-infected
      fibroblasts, negative for the IFN-lambda receptors, induced death of YES-2 or
      T.Tn cells that were co-cultured. Inoculation of YES-2 cells in nude mice, when
      mixed with the Ad/IFN-lambda-infected fibroblasts, resulted in retardation of the
      tumour growth. The growth suppression was not linked with upregulated CD69
      expression on natural killer cells or increased numbers of CD31-positive cells.
      CONCLUSION: Adenovirus/IFN-lambda induced apoptosis, and fibroblast-mediated
      delivery of IFN-lambdas is a potential cancer treatment by inducing direct cell
      death of the target carcinoma.

PMID- 21952624
TI  - Overexpression of cIAP2 contributes to 5-FU resistance and a poor prognosis in
      oral squamous cell carcinoma.
AB  - BACKGROUND: Resistance to 5-fluorouracil (5-FU) is a major obstacle in treating
      oral squamous cell carcinoma (OSCC). However, little is known about apoptosis
      resistance, which contributes to 5-FU resistance in OSCC. METHODS: We focussed on
      the cellular inhibitor of apoptosis protein 2 (cIAP2) on the basis of a DNA
      microarray data using parental and 5-FU-resistant OSCC cell lines. The effects of
      cIAP2 downregulation on 5-FU sensitivity and apoptosis were evaluated. An
      immunohistochemical analysis of cIAP2 and related proteins, cIAP1 and X-linked
      IAP, was performed in 54 OSCC patients who were treated with 5-FU-based
      chemoradiotherapy and surgery. RESULTS: The downregulation of cIAP2 significantly
      enhanced the sensitivity of the 5-FU-resistant cells to 5-FU, with a significant
      increase in apoptosis. The immunohistochemical analysis demonstrated a high cIAP2
      tumour expression to significantly correlate with the pathological response to
      chemoradiotherapy. Furthermore, a Cox regression analysis revealed the cIAP2
      expression status (hazard ratio, 4.91; P=0.037) and the pathological response to
      chemoradiotherapy (hazard ratio, 0.418; P=0.016) to be significant prognostic
      factors for OSCC patients. CONCLUSION: These novel findings demonstrate that
      cIAP2 may represent a potentially useful therapeutic target for improving the
      treatment and survival of OSCC patients, particularly in the setting of 5-FU
      resistance.

PMID- 21952625
TI  - Antibodies against lytic and latent Kaposi's sarcoma-associated herpes virus
      antigens and lymphoma in the European EpiLymph case-control study.
AB  - BACKGROUND: Kaposi's sarcoma-associated herpes virus is associated with primary
      effusion lymphoma and multicentric Castleman's disease. METHODS: Seropositivity
      to lytic and latent Kaposi's sarcoma herpes virus (KSHV) antigens were examined
      in 2083 lymphomas and 2013 controls from six European countries. RESULTS:
      Antibodies against KSHV latent and lytic antigens were detectable in 4.5% and
      3.4% of controls, respectively, and 3.6% of cases (P>0.05). The KSHV
      seropositivity was associated with splenic marginal zone lymphoma (SMZL) (odds
      ratio (OR)=4.11, 95% confidence interval (CI)=1.57-10.83) and multiple myeloma
      (OR=0.31, 95% CI=0.11-0.85). CONCLUSION: The KSHV is unlikely to contribute
      importantly to lymphomagenesis among immunocompetent subjects. However, the
      observed association with SMZL may underline a chronic antigen mechanism in its
      aetiology.

PMID- 21952626
TI  - PTEN regulates colorectal epithelial apoptosis through Cdc42 signalling.
AB  - BACKGROUND: Phosphatase and tensin homologue deleted on chromosome 10 (PTEN)
      regulation of the Rho-like GTPase Cdc42 has a central role in epithelial
      polarised growth, but effects of this molecular network on apoptosis remain
      unclear. METHODS: To investigate the role of Cdc42 in PTEN-dependent cell death,
      we used flow cytometry, in vitro pull-down assays, poly(ADP ribose) polymerase
      (PARP) cleavage and other immunoblots in isogenic PTEN-expressing and -deficient
      colorectal cells (HCT116PTEN(+/+), HCT116PTEN(-/-), Caco2 and Caco2 ShPTEN cells)
      after transfection or treatment strategies. RESULTS: The PTEN knockout or
      suppression by short hairpin RNA or small interfering RNA (siRNA) inhibited Cdc42
      activity, PARP cleavage and/or apoptosis in flow cytometry assays. Transfection
      of cells with wild-type or constitutively active Cdc42 enhanced PARP cleavage,
      whereas siRNA silencing of Cdc42 inhibited PARP cleavage and/or apoptosis.
      Pharmacological upregulation of PTEN by sodium butyrate (NaBt) treatment enhanced
      Cdc42 activity, PARP cleavage and apoptosis, whereas Cdc42 siRNA suppressed NaBt
      induced PARP cleavage. Cdc42-dependent signals can suppress glycogen synthase
      kinase-beta (GSK3beta) activity. Pharmacological inhibition of GSK3beta by
      lithium chloride treatment mimicked effects of Cdc42 in promotion of PARP
      cleavage and/or apoptosis. CONCLUSION: Phosphatase and tensin homologue deleted
      on chromosome 10 may influence apoptosis in colorectal epithelium through Cdc42
      signalling, thus providing a regulatory framework for both polarised growth and
      programmed cell death.

PMID- 21952627
TI  - HPV in exhaled breath condensate of lung cancer patients.
AB  - BACKGROUND: A recent intriguing carcinogenetic hypothesis for lung cancer
      foresees its viral aetiology. The human papilloma virus (HPV) is the main virus
      actually recognised in the pathogenesis of lung cancer. The aim of this study was
      to investigate, for the first time to our knowledge, the presence of HPV in the
      exhaled breath condensate (EBC) of lung cancer patients. MATERIALS AND METHOD: We
      enrolled 89 patients affected by lung cancer and 68 controls. HPV infections were
      investigated in their EBC, paired bronchial brushing and neoplastic lung tissue
      through genotyping. RESULTS: We were able to detect HPV in the EBC, bronchial
      brushing and neoplastic lung tissue. We described the presence of an HPV
      infection in 16.4% of the subjects affected by non-small cell lung cancer, but in
      none of the controls. HPV 16 and 31 turned out to be the most widespread
      genotypes. The HPV positivity in airways as well as in the smoking habit was seen
      to independently increase the individual's susceptibility to developing lung
      cancer. CONCLUSION: When summing up, we demonstrated the possibility to identify
      an HPV infection in the EBC of lung cancer patients; further, we supported the
      notion that the EBC is a suitable tool to study airway colonisation. That being
      said, although further studies are needed to confirm our results, we retain the
      study of HPV in EBC to be very interesting in terms of future programmes
      involving lung-cancer screening.

PMID- 21952628
TI  - Postmenopausal circulating levels of 2- and 16alpha-hydroxyestrone and risk of
      endometrial cancer.
AB  - BACKGROUND: It has been suggested that the relative importance of oestrogen
      metabolising pathways may affect the risk of oestrogen-dependent tumours
      including endometrial cancer. One hypothesis is that the 2-hydroxy pathway is
      protective, whereas the 16alpha-hydroxy pathway is harmful. METHODS: We conducted
      a case-control study nested within three prospective cohorts to assess whether
      the circulating 2-hydroxyestrone : 16alpha-hydroxyestrone (2-OHE1 : 16alpha-OHE1)
      ratio is inversely associated with endometrial cancer risk in postmenopausal
      women. A total of 179 cases and 336 controls, matching cases on cohort, age and
      date of blood donation, were included. Levels of 2-OHE1 and 16alpha-OHE1 were
      measured using a monoclonal antibody-based enzyme assay. RESULTS: Endometrial
      cancer risk increased with increasing levels of both metabolites, with odds
      ratios in the top tertiles of 2.4 (95% CI=1.3, 4.6; P(trend)=0.007) for 2-OHE1
      and 1.9 (95% CI=1.1, 3.5; P(trend)=0.03) for 16alpha-OHE1 in analyses adjusting
      for endometrial cancer risk factors. These associations were attenuated and no
      longer statistically significant after further adjustment for oestrone or
      oestradiol levels. No significant association was observed for the 2-OHE1 :
      16alpha-OHE1 ratio. CONCLUSION: Our results do not support the hypothesis that
      greater metabolism of oestrogen via the 2-OH pathway, relative to the 16alpha-OH
      pathway, protects against endometrial cancer.

PMID- 21952629
TI  - Fructose malabsorption: how much fructose can a healthy subject tolerate?
AB  - BACKGROUND/AIMS: In a prospective study, we evaluated fructose absorption
      capacity in 17 healthy female volunteers aged 16-27 years. METHODS: All
      volunteers underwent analysis of their daily food intake diary and standardized
      breath tests. The volunteers were challenged consecutively with oral intake of
      50, 25 and 15 g of fructose. RESULTS: The average daily ingestion of fructose
      (19.54 +/- 14.95 g) was not different between volunteers with positive and
      negative breath tests. On day 1, 53% of subjects exhibited a significant (>=20
      ppm) increase in breath hydrogen and gastrointestinal symptoms upon challenge
      with 50 g of fructose. Moreover, 37.5% of the volunteers with a negative breath
      test became positive upon a second challenge with 50 g of fructose but remained
      asymptomatic. On day 2, 1 of the 9 volunteers (12.5%) with a positive breath test
      on day 1 exhibited an asymptomatic positive breath test upon exposure to 25 and
      15 g of fructose on day 3. The 8 volunteers with a negative test (25 g of
      fructose) remained negative after a second exposure to 25 g of fructose.
      CONCLUSION: The results of this study indicate that hydrogen breath tests with
      fructose challenge of 50 g of fructose are inappropriate to characterize
      clinically significant fructose malabsorption.

PMID- 21952630
TI  - Reactivity studies of a corrole germanium hydride complex with aldehydes, olefins
      and alkyl halides.
AB  - The tris(pentafluorophenyl) corrole germanium hydride complex (TPFC)Ge-H was
      prepared by the reduction of (TPFC)Ge-OCH(3) with NaBH(4). The reactivity of
      (TPFC)Ge-H with series of aldehydes, olefins and alkyl halides to produce alpha
      hydroxy alkyl and alkyl complexes was studied.

PMID- 21952631
TI  - Rattle-type microspheres as a support of tiny gold nanoparticles for highly
      efficient catalysis.
AB  - SiO(2)/poly(ethyleneglycol dimethacrylate) (PEGDMA) rattle-type microspheres
      loaded with tiny sized gold nanoparticles (~2 nm) were prepared through a facile
      and novel method. Catalyzed reduction of 4-nitrophenol with NaBH(4) demonstrated
      that this rattle-type microsphere possessed high catalytic efficiency.

PMID- 21952632
TI  - Good aerobic or muscular fitness protects overweight men from elevated oxidized
      LDL.
AB  - INTRODUCTION: Oxidized LDL (ox-LDL) is associated with lifestyle diseases such as
      cardiovascular diseases, metabolic syndrome, and type 2 diabetes. The present
      study investigated the association between ox-LDL and overweight/obesity and how
      cardiorespiratory or muscle fitness affects this association. METHODS: Healthy
      young (mean age = 25.1 yr, range = 18-48 yr) men (n = 831) were divided into
      normal-weight (n = 486), overweight (n = 269), and obese (n = 76) groups
      according to their body mass index (BMI). The participants underwent physical
      fitness tests (maximal oxygen uptake with bicycle ergometer and muscle fitness
      index using series of muscle endurance tests), a general health examination
      including determination of lipid profile, and a detailed questionnaire. Subjects
      were further divided into six subgroups according to BMI (normal vs overweight)
      and physical fitness (fitness tertiles: unfit, average, fit). Age and smoking
      were used in the statistical analysis as covariates. RESULTS: In overweight and
      obese participants, the concentrations of ox-LDL (14%/32%) and the ratio of ox
      LDL/HDL cholesterol (32%/68%) were higher compared with subjects with normal
      weight (P < 0.005, in all). In BMI and cardiovascular fitness subgroups, ox-LDL
      (23%, P < 0.0001) and the ox-LDL/HDL cholesterol ratio (45%, P < 0.0001) were
      higher in the overweight/unfit subgroup when compared with the normal
      weight/unfit subgroup, whereas no differences were observed between the
      overweight/fit and normal-weight/fit subjects. Among the BMI and muscle fitness
      subgroups, ox-LDL (24%, P < 0.0001) and the ox-LDL/HDL cholesterol ratio (51%, P
      < 0.0001) were higher in the overweight/unfit group compared with the normal
      weight/unfit group. CONCLUSIONS: Overweight and obesity are associated with ox
      LDL lipids and serum conventional lipids. However, both good cardiorespiratory
      fitness and muscular fitness seem to protect overweight subjects from the
      atherogenic lipid profile.

PMID- 21952633
TI  - Anaerobic capacity as a determinant of performance in sprint skiing.
AB  - PURPOSE: As cross-country sprint competitions rely on maximal-effort durations of
      ~3 min, a significant anaerobic energy contribution is expected. Anaerobic energy
      production during supramaximal exercise has been estimated in different sports
      from the accumulated oxygen deficit (SigmaO2 deficit) but, to date, not in cross
      country skiing. Therefore, this study investigated the relative contribution of
      the aerobic and anaerobic energy systems to performance in ski skating sprint
      time trials using V1 and V2 techniques. METHODS: Twelve elite senior male cross
      country skiers participated in the study (24 +/- 3 yr, 183 +/- 5 cm, 79 +/- 7 kg,
      VO(2max) = 72 +/- 3 mL.kg-1.min-1 or 5.7 +/- 0.5 L.min-1). Three submaximal
      trials (4 degrees -6 degrees ), one VO(2max) test (8 degrees ), and one
      performance test (7 degrees , 600 m) were performed both in the V1 and in the V2
      ski skating technique on a roller ski treadmill. RESULTS: SigmaO2 deficit was ~60
      mL.kg-1 and contributed to ~26% of the total energy release during the ~170-s
      time trials. Low to moderate correlations (r = 0.09-0.51) were found between O2
      cost of skiing, fractional utilization of VO(2peak), fractional utilization, and
      600-m time. However, a moderate to strong correlation was found between SigmaO2
      deficit and 600-m time in both the V1 (r = -0.75) and the V2 tests (r = -0.64)
      (both P < 0.05). No significant differences were found between techniques
      according to 600-m time or physiological responses. CONCLUSIONS: The contribution
      from anaerobic energy systems was ~26% and seemed independent of technique. In a
      group of elite skiers, the difference in roller ski treadmill sprint performance
      is more related to differences in anaerobic capacity than maximal aerobic power
      and O2 cost.

PMID- 21952634
TI  - Physical activity and total antioxidant capacity across an adult lifespan of men.
AB  - PURPOSE: The aim of the study was to determine the association between the long
      term physical activity (PA) and the total antioxidant capacity (TAC) of blood
      serum and their association with coexisting risk factors of cardiometabolic
      diseases in a group of relatively healthy men. METHODS: The research was
      conducted among 422 males age 19.2-89.8 yr, either sedentary or involved in
      recreational sports activities. Anthropometric measurements, lipid profile, and
      measurement of glucose and uric acid levels were performed in every man. Current
      PA, historical PA, and aerobic fitness (physical working capacity) were assessed.
      TAC was determined with two spectrophotometric methods: the ferric reducing
      ability of serum (TAC-FRAS) and 2,2-diphenyl-1-picryl-hydrazyl (TAC-DPPH) tests.
      RESULTS: TAC was not related to the age of the subjects. Higher current and
      historical PA were associated with a more favorable cardiometabolic risk profile
      but not TAC. In fact, current PA level was connected with lower values of TAC
      FRAS. Values of both TAC-FRAS and TAC-DPPH decreased with an increase of aerobic
      capacity. Individuals with coexisting anthropometric and biochemical risk factors
      of cardiovascular diseases and with elevated values of arterial pressure had
      higher TAC. Values of both TAC-FRAS (r = 0.66) and TAC-DPPH (r = 0.39) were
      strongly positively correlated with uric acid level. CONCLUSIONS: Overweight,
      obesity, higher blood pressure, unfavorable blood lipid profile, and especially
      higher uric acid levels are connected with greater TAC of blood serum across an
      adult man's life. High PA and fitness are associated with a more favorable
      overall risk profile of cardiovascular and metabolic diseases but are related to
      lower TAC.

PMID- 21952635
TI  - Training preserves the intestinal cytokine response to acute exercise in older
      mice.
AB  - Long-term freewheel training in young animals decreases intestinal lymphocyte
      expression of inflammatory cytokines and apoptotic proteins. Little is known
      about these responses in older animals. PURPOSE: This study aimed to evaluate the
      effect of training on intestinal lymphocyte expression of proinflammatory and
      anti-inflammatory cytokines and proapoptotic and anti-apoptotic proteins after an
      acute exercise challenge in older mice. METHODS: Eighty female C57BL/6 mice, aged
      11 months at the start of the study, were randomized to two exercise training
      conditions for 4 months: access to in-cage running wheels (WR, n = 40) or to a no
      running-wheel condition (NWR, n = 40). After 4 months of training, WR and NWR
      mice underwent a single bout of treadmill exercise with immediate sacrifice (n =
      20 and n = 20, respectively) or were sedentary with exposure only to treadmill
      noise and vibrations without actual running (n = 20 and n = 20, respectively).
      Plasma 8-iso-PGF2alpha and corticosterone levels and intestinal lymphocyte
      cytokine (tumor necrosis factor (TNF)-alpha, interleukin (IL)-beta, IL-10) and
      apoptotic protein (caspase-3, caspase-7, Bcl-2) expression were assessed by
      enzyme immunoassay and by Western blotting. RESULTS: Older (15-16 months) WR mice
      had greater intestinal lymphocyte expression of proinflammatory (TNF-alpha, IL
      1beta) and anti-inflammatory (IL-10) cytokines and proapoptotic (caspase-3,
      caspase-7) proteins and decreased expression of antiapoptotic (Bcl-2) proteins
      after acute treadmill challenge relative to older WR sedentary mice. Older NWR
      mice had few changes in intestinal lymphocyte cytokine or apoptotic protein
      expression after an acute treadmill exercise relative to NWR sedentary mice.
      CONCLUSIONS: Long-term freewheel training preserves the intestinal lymphocyte
      cytokine and apoptotic protein responses in older mice similar to that previously
      reported for young animals. Older NWR (untrained) mice have blunted
      responsiveness (cytokines and apoptotic protein expression) after acute exercise
      suggestive of immunosenescence.

PMID- 21952636
TI  - Within-subject variation in hemoglobin mass in elite athletes.
AB  - Illicit autologous blood transfusion to improve performance in elite sport is
      currently undetectable, but the stability of longitudinal profiles of an
      athlete's hemoglobin mass (Hbmass) might be used to detect such practices.
      PURPOSE: Our aim was to quantify within-subject variation of Hbmass in elite
      athletes, and the effects of potentially confounding factors such as reduced
      training or altitude exposure. METHODS: A total of 130 athletes (43 females and
      87 males) were measured for Hbmass an average of six times during a period of
      approximately 1 yr using carbon monoxide rebreathing. Linear mixed models were
      used to quantify within-subject variation of Hbmass and its associated analytical
      and biological components for males and females, as well as the effects of
      reduced training and moderate altitude exposure in certain athletes. RESULTS: The
      maximum within-subject coefficient of variation (CV) for Hbmass was 3.4% for
      males and 4.0% for females. The analytical CV was ~2.0% for both males and
      females, and the long-term biological CV, after allowing for analytical
      variation, was 2.8% for males and 3.5% for females. On average, self-reported
      reduced training resulted in a 2.8% decrease in Hbmass and altitude exposure
      increased Hbmass by 1.5% to 2.9%, depending on the duration and type of exposure.
      CONCLUSIONS: The within-subject CV for Hbmass of ~4% indicates that athletes may
      experience changes up to ~20% with a 1-in-1000 probability. Changes of this
      magnitude for measures taken a few months apart suggest that Hbmass has a limited
      capacity to detect autologous blood doping. However, changes in Hbmass may be a
      useful indicator when combined with other measures of blood manipulation.

PMID- 21952637
TI  - Cobalt stress in Escherichia coli and Salmonella enterica: molecular bases for
      toxicity and resistance.
AB  - Cobalt (Co) is present in trace amounts in the environment but it can be toxic
      when it accumulates in cells. The question of how Co produces its toxic effects
      and how living organisms protect themselves from, and resist to, such a stress
      remains to be clarified. Studies pertaining to these issues were recently carried
      out in Escherichia coli and Salmonella enterica. Iron-sulfur proteins were
      identified as primary targets of Co ions. Perturbation of iron homeostasis,
      oxidative stress and possible effects on sulfur assimilation were noticed. Cells
      were found to respond by up-regulating genes involved in the biosynthesis of Fe-S
      clusters as well as genes involved in Co efflux. These data are summarized in
      this review article to provide a preliminary general view of Co toxicity
      mechanisms in these two bacterial models.

PMID- 21952638
TI  - [I Latin American guidelines for the diagnosis and treatment of Chagas
      cardiomyopathy].

PMID- 21952640
TI  - Nanoporous titanium borophosphates with rigid gainesite-type framework structure.
AB  - Nanoporous titanium borophosphates have been synthesized which exhibit a rigid
      gainesite-type framework of polyhedra. The open-framework character is supported
      by the reversibility of de- and rehydration processes.

PMID- 21952639
TI  - NIRF constitutes a nodal point in the cell cycle network and is a candidate tumor
      suppressor.
AB  - In biological networks, a small number of "hub" proteins play critical roles in
      the network integrity and functions. The cell cycle network orchestrates
      versatile cellular functions through interactions between many signaling modules,
      whose defects impair diverse cellular processes, often leading to cancer.
      However, the network architecture and molecular basis that ensure proper
      coordination between distinct modules are unclear. Here, we show that the
      ubiquitin ligase NIRF (also known as UHRF2), which induces G1 arrest, interacts
      with multiple cell cycle proteins including cyclins (A2, B1, D1 and E1), p53 and
      pRB, and ubiquitinates cyclins D1 and E1. Consistent with its versatility, a
      bioinformatic network analysis demonstrated that NIRF is an intermodular hub
      protein that is responsible for the coordination of multiple network modules.
      Notably, intermodular hubs are frequently associated with oncogenesis. Indeed, we
      detected loss of heterozygosity of the NIRF gene in several kinds of tumors. When
      a cancer outlier profile analysis was applied to the Oncomine database, loss of
      the NIRF gene was found at statistically significant levels in diverse tumors.
      Importantly, a recurrent microdeletion targeting NIRF was observed in non-small
      cell lung carcinoma. Furthermore, NIRF is immediately adjacent to the single
      nucleotide polymorphism rs719725, which is reportedly associated with the risk of
      colorectal cancer. These observations suggest that NIRF occupies a prominent
      position within the cell cycle network, and is a strong candidate for a tumor
      suppressor whose aberration contributes to the pathogenesis of diverse
      malignancies.

PMID- 21952642
TI  - Unusual course of myelodysplastic syndrome with presumed familial origin.

PMID- 21952643
TI  - Renal stone disease: a commentary on the nature and significance of Randall's
      plaque.

PMID- 21952644
TI  - Acetophenone hydrogenation over a Pd catalyst in the presence of H2O and CO2.
AB  - The addition of carbon dioxide and water enhances acetophenone hydrogenation
      activity over an activated carbon-supported palladium catalyst, and 1
      phenylethanol can be easily recovered without distillation and neutralization.
      Two liquid phases (water and acetophenone) are indispensable for enhancement of
      the hydrogenation rate.

PMID- 21952645
TI  - The oxidative conversion of the N,S-bridged complexes [{RhLL'(MU-X)}2] to
      [(RhLL')3)(MU-X)2]+ (X = mt or taz): a comparison with the oxidation of N,N
      bridged analogues.
AB  - The structures of [{RhLL'(MU-X)}(2)] [LL' = cod, (CO)(2), (CO)(PPh(3)) or
      {P(OPh)(3)}(2); X = mt or taz], prepared from [{RhLL'(MU-Cl)}(2)] and HX in the
      presence of NEt(3), depend on the auxiliary ligands LL'. The head-to-tail
      arrangement of the two N,S-bridges is accompanied by a rhodium-eclipsed
      conformation for the majority but the most hindered complex,
      [{Rh[P(OPh)(3)](2)(MU-taz)}(2)], uniquely adopts a sulfur-eclipsed structure. The
      least hindered complex, [{Rh(CO)(2)(MU-mt)}(2)], shows intermolecular stacking of
      mt rings in the solid state. The complexes [{RhLL'(MU-X)}(2)] are chemically
      oxidised to trinuclear cations, [(RhLL')(3)(MU-X)(2)](+), most probably via
      reaction of one molecule of the dimer, in the sulfur-eclipsed form, with the
      fragment [RhLL'](+) formed by oxidative cleavage of a second.

PMID- 21952646
TI  - Rosacea-like demodicosis mimicking cutaneous lymphoma.

PMID- 21952647
TI  - Mononuclear Zn(II)- and Cu(II)-complexes of a hydroxynaphthalene-derived
      dipicolylamine: fluorescent sensing behaviours toward pyrophosphate ions.
AB  - Mononuclear Zn(II)-DPA and Cu(II)-DPA complexes crafted on 2-hydroxy-6
      cyanonaphthalene fluorophore selectively recognize PPi over ATP and other anions
      including inorganic phosphates in aqueous medium, showing turn-on type
      fluorescence enhancements. Coordination of a hydroxyl group of the fluorophore,
      directly or in alkoxy form, to the central metal ion is crucial for the sensing
      processes. Both the complexes elicit a fluorescence increase in a time-dependent
      fashion.

PMID- 21952648
TI  - Facile creation of hierarchical PDMS microstructures with extreme underwater
      superoleophobicity for anti-oil application in microfluidic channels.
AB  - Composition modification and surface microstructures have been widely utilized in
      interface science to improve the surface performance. In this paper, we observed
      a significant improvement of oil contact angle (CA) from 66 +/- 2 degrees  to 120
      +/- 4 degrees  by introducing a radical silanol group on a flat PDMS surface
      through oxygen plasma pretreatment. By combining surface microstructures and
      plasma modification, we produced three kinds of superoleophobic surfaces: 20 MUm
      pitch micropillar arrays, 2.5 MUm pitch micropillar arrays and gecko foot-like
      hierarchical microstructures. Among them, the hierarchical surface with high
      surface roughness showed extreme underwater superoleophobicity, which featured
      ultrahigh CA (175 +/- 3 degrees ) and ultrasmall sliding angle (<1 degrees ).
      Quantitative measurements demonstrated that these superoleophobic surfaces
      exhibited distinct adhesive behaviors, by which they were interpreted as
      Wenzel's, Cassie's and the Lotus state, respectively. A microfluidic channel with
      superoleophobic microstructures was further created by novel curve-assisted
      imprint lithography, and the characterization based on anti-oil contamination
      applications was carried out and discussed. We believe that the superoleophobic
      surfaces will power broad applications in oil microdroplet transportation, anti
      oil channels and droplet microfluidic systems.

PMID- 21952649
TI  - Use of HC2 to triage women with borderline and mild dyskaryosis in the UK.

PMID- 21952650
TI  - Role of the conformational changes brought in the arms of the 1,3-di-capped
      conjugate of calix[4]arene (L) in turning on the fluorescence of L by Hg2+.
AB  - A new 1,3-di-capped calix[4]arene conjugate of salicylidene (L) has been
      synthesized, characterized and the structure has been established by single
      crystal XRD. L shows selectivity towards Hg(2+) in ethanol by turn-on
      fluorescence among the biologically important metal ions studied. The species of
      recognition has been modeled by DFT computational calculations to result in
      conformational changes in the arms that support the turn-on fluorescence
      behaviour.

PMID- 21952651
TI  - CdSe quantum dots as labels for sensitive immunoassay of cancer biomarker
      proteins by electrogenerated chemiluminescence.
AB  - A sensitive and specific immunoassay method for detecting alpha-fetoprotein (AFP)
      based on electrogenerated chemiluminescence (ECL) was described. ECL could
      perform detection for a series of different concentrations of AFP. CdSe quantum
      dots (QDs) were used as labels and were linked to AFP antibody (anti-AFP, the
      secondary antibody, Ab2*). Immunoassay was carried out on a modified electrode
      using a sandwich assay approach, where anti-AFP (Ab1) was covalently bound to the
      surface of an Au electrode to be allowed to capture AFP specifically. Afterwards,
      Ab2* was allowed to bind selectively to the captured AFP. The non-specific
      adsorption was negligible. In the presence of H(2)O(2), the ECL intensity
      increased with the increase of AFP, which indicated that an immunosensor for AFP
      was constructed. The detection of AFP based on measuring the ECL intensity of
      CdSe without the enzyme and mediator can promote the stability of the
      immunosensor. The linear range of the AFP assay was from 0.002 to 32 ng mL(-1).
      Furthermore, the immunosensor showed high sensitivity, good precision, stability,
      and reproducibility and could be used for the detection of real samples with
      consistent results in comparison with those obtained by the enzyme-linked
      immunosorbent assay (ELISA) method. The strategy was successfully demonstrated as
      a simple, cost-effective, specific, and potential method to detect AFP in
      practical samples.

PMID- 21952652
TI  - Rational control of a polyacetylene helix by a pendant rotaxane switch.
AB  - Polyacetylene bearing a pendant rotaxane moiety with an optically active wheel
      component was synthesized to realize reversible structural control of its helical
      structure by position control of the wheel component. Polyacetylene formed a one
      handed helical structure only when the optically active wheel component moved
      close to the main chain.

PMID- 21952653
TI  - Effects of electrocautery to provoke endovascular thermal injury.
AB  - PURPOSE: To investigate the effects of a new electrocautery device to provoke
      endovascular venous thermal injury. METHODS: An experimental endovascular
      electrocautery was placed inside eight ex-vivo bovine saphenous veins models.
      Each one was divided in eight segments and progressive intensities of electric
      energy liberated. The macroscopic and microscopic effects were analyzed. RESULTS:
      Forty bovine saphenous veins segments were studied. The higher the electric
      energy applied the greater the nuclear picnosis and more intense the
      cytoplasmatic shrinkage and electrocoagulation effects. CONCLUSION: The
      experimental endovascular electrocautery device demonstrated to be both capable
      of inducing the destruction of the intimal layers of the studied vein model and
      provoke endovascular thermal injury.

PMID- 21952654
TI  - Evaluation of castor oil-based polyurethane membranes in rat bone-marrow cell
      culture.
AB  - PURPOSE: To evaluate three methods to isolate rats MSCs and to analyze the
      potential of a castor oil polyurethane base membrane as a scaffold for MSCs.
      METHODS: Four male Wistar rats, aged 20-30 days were used. Bone marrow aspirates
      from femur and tibia were harvested using DMEM high glucose and heparin. The cell
      culture was performed in three different ways: direct culture and two types of
      density gradients. After 15 days, was made the 1st passage and analyzed cell
      viability with markers Hoerscht 33342 and propidium iodide. The MSCs were
      characterized by surface markers with the aid of flow cytometry. After this,
      three types of castor oil polyurethane membranes associated with the MSCs were
      kept on the 6-well plate for 5 days and were analyzed by optical microscopy to
      confirm cell aggregation and growth. RESULTS: Separation procedures 1 and 2
      allowed adequate isolation of MSCs and favored cell growth with the passage being
      carried out at 70% confluence after 15 days in culture. The cells could not be
      isolated using procedure 3. When the 3 castor oil polyurethane membrane types
      were compared it was possible to observe that the growth of MSCs was around 80%
      in membrane type 3, 20% in type 2, and 10% in type 1. CONCLUSION: Both Ficoll
      Hypaque densities allow isolation of rat MSCs, and especially castor oil-based
      membrane type 3 may be used as a scaffold for MSCs.

PMID- 21952655
TI  - Effects of broccoli extract on biodistribution and labeling blood components with
      99mTc-GH.
AB  - PURPOSE: People consume vegetables without the knowledge of the side effects of
      the biological and chemical contents and interactions between
      radiopharmaceuticals and herbal extract. To this end, current study is focused on
      the effects of broccoli extract on biodistribution of radiolabeled glucoheptonate
      ((99m)Tc-GH) and radiolabeling of blood components. METHODS: GH was labeled with
      (99m)Tc. Quality control studies were done utilizing TLC method. Biodistribution
      studies were performed on male rats which were treated via gavage with either
      broccoli extract or SF as control group for 15 days. Blood samples were withdrawn
      from rats' heart. Radiolabeling of blood constituents performed incubating with
      GH, SnCl2 and (99m) Tc. RESULTS: Radiochemical yield of (99m)Tc-GH is 98.46+/
      1.48 % (n=8). Biodistribution studies have shown that according to the control,
      the treated group with broccoli has approximately 10 times less uptake in kidney.
      The percentage of the radioactivity ratios of the blood components is found to be
      same in both groups. CONCLUSIONS: Although there is no considerable effect on the
      radiolabeling of blood components, there is an outstanding change on the
      biodistribution studies especially on kidneys. The knowledge of this change on
      kidney uptake may contribute to reduce the risk of misdiagnosis and/or repetition
      of the examinations in Nuclear Medicine.

PMID- 21952656
TI  - Electroacupuncture versus morphine for the postoperative control pain in dogs.
AB  - PURPOSE: [corrected] To compare the postoperative analgesic effects of
      electroacupuncture, morphine or sham acupuncture in dogs undergoing mastectomy.
      METHODS: Thirty client-owed dogs undergoing to mastectomy were randomly assigned
      to three groups of 10 animals each and received either morphine (T-M), the
      electroacupuncture (T-EA) or sham procedure (T-Sham). Pre-anesthetic medication
      was acepromazine (0.05 mg kg(-1), IM). Anesthesia was induced with propofol (4 to
      5 mg kg(-1), IV) and maintained with isoflurane. Postoperatively pain degree was
      assessed using a numerical rating scale. Dogs were scored at 1, 3, 6 and 12 hours
      post-extubation. If the pain score was >=6, supplemental morphine was
      administered. Serum cortisol concentration was measured before pre-anesthetic
      medication, at 45 minutes after the anesthetic induction, and at 1, 3 and 6 hours
      post-extubation. RESULTS: The pain score did not differ among the treatments, but
      rescue analgesia was lower in the T-EA group (2 of 10 dogs), when compared with T
      Sham (6 of 10 dogs) and T-M (6 of 10 dogs) groups. Serum cortisol concentration
      did not differ among the treatments. CONCLUSION: Electroacupuncture reduces the
      postoperative analgesic requirement and promotes satisfactory analgesia in dogs
      undergoing mastectomy.

PMID- 21952657
TI  - Technique of blind tracheal intubation in rabbits (Oryctolagus cuniculi)
      supported by previous maneuver of esophageal cannulization.
AB  - PURPOSE: To describe and evaluate a modified technique of blind orotraqueal
      intubation in rabbits, by supporting of previous cannulization of the esophagus.
      METHODS: Twelve New Zealand rabbits, weighing between 2,780 a 4,140 kg were
      anesthetized with xilazine (3mg/Kg) and ketamine (20mg/Kg). The animals were
      positioned in ventral decubitus with the head hyperextend. With one of the hands
      the anesthetist with the index and thumb fingers positioned in the labial
      fissures carry on the opening of animal oral cavity. The esophagus was previously
      cannulized with a tube # 3.5 (3.5mm ID), obstructing its lumen. The trachea lumen
      was intubated with a probe # 2.5 (2.5mm ID). The positioning of the probe was
      confirmed through the oscillatory movement of a gauze filament put at outside
      extremity of tube, resulting from the inspiratory and expiratory flow. RESULTS:
      The success index was of 100%. CONCLUSIONS: This technique is of easy execution,
      high success index, sparing the use of several devices for visualization of the
      larynx and glottis. No complications were observed. It also serves for short
      period training of human resources.

PMID- 21952658
TI  - Morphological findings in the tracheal epithelium of dogs exposed to the
      inhalation of poorly conditioned gases under use of an endotracheal tube or
      laryngeal mask airway.
AB  - PURPOSE: To study morphological findings in the tracheal epithelium of dogs
      exposed to the inhalation of poorly conditioned gases under use of an
      endotracheal tube (ET) or laryngeal mask airway (LMA). METHODS: Twelve dogs
      randomly were allocated to two groups: ET group (n-6) and LMA group (n-6),
      anaesthetized and mechanically ventilated, without CO(2) reabsorption.
      Haemodynamic and ventilatory parameters, tympanic temperature, temperature,
      relative and absolute humidity of the ambient and inhaled gases were analyzed
      during three hours. The animals were submitted to euthanasia and biopsies were
      carried out along the tracheal segment to morphological study. Three healthy dogs
      were used to morphological control. RESULTS: Inhaled gas temperature was
      maintained between 24oC and 26oC, relative humidity between 10% and 12%, and
      absolute humidity between 2 - 3 mg H(2)O.L(-1) with no significant differences
      between groups. In both groups, histological analysis showed epithelial
      inflammation and congestion in the corion and scanning electron microscopy showed
      ciliary grouping and disorganization. Transmission electron microscopy showed
      higher alterations in ET group than LMA group as widening of cell junctions,
      ciliary disorientation, cytoplasmic vacuolization, nuclear abnormalities,
      picnosis and chromatin condensation. CONCLUSION: LMA determined less pronounced
      changes in the tracheal epithelium in dogs exposed to the inhalation of poorly
      conditioned gases.

PMID- 21952659
TI  - Experimental dry socket: microscopic and molecular evaluation of two treatment
      modalities.
AB  - PURPOSE: To evaluate two treatment modalities of dry socket in rats and to
      discuss the first findings of the molecular analysis in this experimental model.
      METHODS: 84 rats underwent a tooth extraction were divided in 4 groups: I
      uninfected socket (control), II-infected socket without any treatment, III
      infected socket treated with irrigation of 2% sodium iodide and 3% hydrogen
      peroxide solution, IV-infected socket submitted to curettage, irrigation with
      physiological saline solution and fulfilled with metronidazole paste as base. The
      groups were subdivided in postoperative sacrifice periods: 6/15/28 days. A
      quantitative and a qualitative microscopic analysis was performed. Also, a
      quantitative analysis was performed using a RealTimePCR to evaluate the genes
      expression in the wound healing: Collagen Type I/COL-I, vascular endothelial
      growth factor/VEGF, osteocalcin/OCN, alkaline phosphatase/ALP, runt-related
      transcription factor 2/RUNX2 and tumor necrosis factor alpha/TNF-alpha. RESULTS:
      The group I showed higher bone formation, followed by groups IV, III, II
      respectively. The group II presented higher inflammatory infiltrate and the wound
      healing was delayed compared with other groups. It was obtained a significant
      positive correlation between bone neoformation and the expression of OCN and
      RUNX2, inflammatory infiltrate with TNF-alpha and a negative correlation between
      bone neoformation and TNF-alpha. CONCLUSION: No significant difference was found
      between the treatments.

PMID- 21952660
TI  - Healing activity of laser InGaAlP (660nm) in rats.
AB  - PURPOSE: To evaluate the effect the healing activity of diode laser Indium
      Gallium Aluminum Phosphorus (InGaAlP) e660nm on healing of surgical wounds in
      rats. METHODS: Fifty-four female Wistar rats were used, divided into three groups
      (n=18) and subdivided into three subgroups (n=6) to be studied in 5, 10 and
      15(th) days after surgical procedures. The wound was induced in the dorsal
      cervical using punch. The lesions were irradiated on alternate days with InGaAlP
      laser, the energy densities of 3J/cm(2) (L3) or 6J/cm(2) (L6). The control group
      received no irradiation. At 5, 10 and 15(th) days after surgery the animals were
      euthanized and the repair area was removed and histological sections were stained
      with hematoxylin-eosin and picrossirius. We evaluated macroscopic and
      histological lesions in the times cited, as well as morphometric analysis of
      angiogenesis and collagen content. RESULTS: The wound healing activity InGaAlP
      laser was evidenced by increased angiogenesis group L3 and L6 in relation to
      control group (CG) at the 5(th) day (p=0.0001) and decreased polymorphonuclear
      infiltrate and hemorrhage (p=0.045 and p=0.07 respectively) in the groups L3 and
      L6 in relation to control group (GC). On the 10 and 15(th) days was also observed
      in groups treated with laser L3 and L6 stimulation was pronounced fibroplasia
      (p=0.0003 and p=0.034 respectively) when compared with the control group (CG).
      CONCLUSION: The InGaAlP laser acted positively on the healing of skin wounds in
      rats.

PMID- 21952661
TI  - Gel from unripe Musa sapientum peel to repair surgical wounds in rats.
AB  - PURPOSE: To determine the optimum concentration of a gel obtained from unripe
      banana (Musa sapientum) peel for wound treatment in rats. METHODS: A randomized
      triple blind study was conducted with 40 Wistar rats, which were divided into 4
      groups: CG, control group; G2%, 2% gel concentration group; G4%, 4% gel
      concentration group; and G10%, 10 % gel concentration group. The banana peel gel
      was applied daily, for 7 days, to a 4-cm(2) wound created on the back of each
      animal of all groups. After this period, the wounds were biopsied. Statistical
      analysis was carried out using the Kruskal-Wallis test complemented by the
      Student-Newman-Keuls test. RESULTS: Macroscopic examination revealed that partial
      epithelialization occurred in all groups. Wound contraction was also observed in
      all groups and ranged from 1.38 to 1.57 mm in the study groups, and from 1.03 to
      1.10 mm in the control group, with significant differences (p < 0.05) between the
      groups: CG and G10%, G2% and G4%, G2% and G10%. The interquartile deviation was
      smaller between the groups CG and G4%. CONCLUSION: The 4% gel obtained from
      unripe banana peel (G4%) resulted in better epithelialization of wounds healed by
      secondary intention compared with other gel concentrations.

PMID- 21952662
TI  - Comparative study of the areas of osteochondral defects produced in the femoral
      condyles of rabbits treated with gel of sugarcane biopolymer.
AB  - PURPOSE: To measure the healed areas of osteochondral defects produced in femoral
      condyles of rabbits filled with biopolymer sugar cane gel and to compare these
      with those of the control group at 90, 120 and 180 days. METHODS: A study was
      made of 16 New Zealand rabbits, 6 and 7 months old, weighing between 2 and 2.5
      kg. Defects of 3.2 x 4 mm were made, with trephine, in the femoral condyles of
      the right and left knees. As to the study group defects of the medial and lateral
      condyles of the right knee were used which were filled with Biopolymer Sugar Cane
      Gel; as to the Control Group defects of the medial and lateral condyles of the
      left t knees were used which were left open for natural healing. The defects were
      analyzed at 90, 120 and 180 days after surgery. After euthanasia, the knees were
      removed and fixed in Bouin's solution for later digital photographic
      documentation with a digital camera. The areas healed were measured in both the
      study and control groups using the images obtained from an Image-J((r)) program.
      Statistical analysis was conducted using the non-parametric Mann-Whitney test.
      RESULTS: There were no significant differences between the means of the healed
      areas in the study and control groups at 90, 120 and 180 days after surgery.
      CONCLUSION: The dimension of the healed areas of the defects treated with the
      biopolymer sugar-cane gel in the study group was similar to those of the control
      group, which healed naturally.

PMID- 21952663
TI  - Clinical importance and prevalence of testicular microlithiasis in pediatric
      patients.
AB  - PURPOSE: To evaluate the prevalence of testicular microlithiasis among pediatric
      patients with inguinoscrotal affections. METHODS: Between January 2005 and
      January 2010, we evaluated, prospectively 1504 children ranging from 1 to 15
      years with inguinoscrotal affections with a high-frequency ultrasound system,
      which employs a 10-MHz transducer. RESULTS: Testicular microlithiasis was
      identified in 20 testes of eleven children (0.71% of 1504 patients evaluated),
      through an ultrasound scan. Testicular microlithiasis was found in 5 children
      with cryptorchidism (3.93% of 127 patients), 4 children with retractile testes
      (14.8% of 27 patients), 1 child with a hypotrophic testis (100% of 1 patient),
      and 1 child with inguinal hernia (0.07% of 1349 patients). The children with
      testicular microlithiasis were submitted to annual physical examinations and
      ultrasound evaluations. CONCLUSIONS: Testicular microlithiasis was a rare
      condition and occurred in 0.7% of the subjects studied. The association with
      cryptorchidism, retractile and hypotrophic testis was significant.

PMID- 21952664
TI  - Telescopic straight ileo-anal anastomosis in dogs.
AB  - PURPOSE: To study outcomes and functional results of a telescopic straight ileo
      anal anastomosis. METHODS: Thirty-six mongrel dogs were submitted to total
      proctocolectomy and telescopic straight ileo-anal anastomosis (ileal mucosa
      submucosa pulled-through the rectal cuff). They were divided in 3 groups,
      sacrificed after one, two or eight weeks after the initial procedure. Gross and
      microscopic (degree of cooptation and signs of ischemia) aspects of the
      anastomosis, as well, the aspect of defecation were analyzed. RESULTS: On
      microscopy all anastomosis analysed showed a continuous epithelial line and were
      considered good. After two-months no signs of ischemia were identified.
      Defecation aspect has considerably changed during the study, so no dogs presented
      solid defecation within the first two weeks, whereas 80% of dogs presented solid
      stools after two months. CONCLUSION: Telescopic ileo-anal anastomosis is a safe
      alternative and may provide good functional results after some small period of
      time.

PMID- 21952665
TI  - Effects of ischemic preconditioning associated to different preservation
      solutions in protecting the intestinal graft.
AB  - PURPOSE: To evaluate the effects of ischemic preconditioning (IPC) associate with
      different preservation solutions, in the protecting of gut. METHODS: Four groups
      of 14 rats underwent laparotomy and collecting 20 cm of ileum, for preservation,
      at 4oC, in Belzer (Belz), Ringer (RL), Celsior (Cs) and Custodiol (Cust)
      solutions, for 24 hours. Prior to collection, half of the animals in each group
      were subjected to IPC. During preservation, in the periods of zero, 12, 18 and 24
      hours, were conducted evaluating the degree of mucosal injury and dosage of
      malondialdehyde acid (MDA). RESULTS: In all periods the RL group, with and
      without IPC, presented MDA values higher than the Belz and Cs. The degree of
      mucosal injury in the non-ipc RLgroup with 12h preservation was higher than the
      others; with 18 and 24h, the RL and Cust had higher degrees of damage than Cs and
      Belz. With IPC, in all periods, the group Cs and Belz had lower degrees of
      injury. CONCLUSION: The Celsior and Belzer solutions had better protective
      effects on the gut and these effects were enhanced by IPC.

PMID- 21952666
TI  - Peripherally inserted central catheters in the neonatal period.
AB  - PURPOSE: Peripherally inserted central catheters (PICC) have been extensively
      used in neonates. However, insertion of these thinnest catheters is a very
      delicate procedure associated with a high failure rate. In our Neonatal Surgical
      Intensive Care Unit, we developed a very easy new PICC insertion and evaluated
      the neonates treated with PICCs which were inserted by using our technique as
      well as catheter features such as success rate, number of insertion attempts,
      reason for removal and complications. METHODS: Information was retrospectively
      collected on all 40 PICCs inserted at Kutahya Evliya Celebi Goverment Hospital
      and Dicle University Hospital during a 6-years period from September 2004 to
      September 2010. RESULTS: A total of 40 PICCs were inserted in 37 patients (26,
      70% males, 11, 30% females) by using new technique. The median age of patients
      was 8.3 days (range 1 to 66 days) and the median weight of patients was 2365 g
      (range 600 to 5000 g). The vein most commonly accessed was long saphenous vein
      (85%). The length of PICCs in the body was 19.6 cm (range 5 cm to 30 cm). The tip
      was located in a central vein in all patients. Surgical abdomen was the most
      common cause for PICC insertion (38%). Duration of catheterization was 7.7+/-5.6
      days (1-F 5.5 days, 2-F 8.6 days). Almost all of the PICCs were inserted
      successfully (40/42, success rate 95%) and in the first venipucture (36/42, 86%).
      Completion of therapy and removed after death were achieved with 87% of PICCs.
      Three minor complications were noted. Minor bleeding in the insertion site which
      was stopped via compression occurred in two neonates. Major complication was not
      seen. No deaths were directly attributed to PICCs use. CONCLUSION: The new
      insertion technique of the neonatal peripherally inserted central catheters may
      be one of the easiest and safest techniques, in comparison to previous techniques
      reported in the literature.

PMID- 21952667
TI  - A novel nickel responsive MerR-like regulator, NimR, from Haemophilus influenzae.
AB  - We have identified a novel regulator from the MerR family of transcription
      factors in the bacterial pathogen Haemophilus influenzae (HI1623; nickel
      associated merR-like Regulator--NimR). NimR regulates the expression of a Ni(2+)
      uptake transporter (NikKLMQO). The promoters for nimR and the nik operon are
      divergent and overlapping and NimR binds at a site between the promoter elements
      for nikKLMQO. Expression of this operon requires NimR and depends on Ni(2+).
      Growth rates of the H. influenzae nimR and nikQ mutants were reduced in
      chemically defined media compared to the wild type and the mutants were unable to
      grow in the presence of EDTA. The mutant strains were less tolerant of acidic pH
      and the wild type Rd KW20 could not tolerate low pH in the presence of
      fluoramide, a urease specific inhibitor, confirming that both nickel transport
      and urea hydrolysis are a central process in pH control. H. influenzae nimR and
      nikQ strains were deficient in urease activity, but this could be specifically
      restored by the addition of excess Ni(2+). NimR did not directly regulate the
      expression of urease genes but the activity of urease requires both nimR and
      nikQ. Purified NimR is a dimer that binds 1 Ni(2+)ion. NimR is the first example
      of a Ni-dependent regulator from the MerR family and targeting a metal ion uptake
      system; it is distinct from NikR the Ni-responsive regulators of the ribbon-helix
      helix family.

PMID- 21952668
TI  - MDMA (ecstasy) effects on actual driving performance before and after sleep
      deprivation, as function of dose and concentration in blood and oral fluid.
AB  - RATIONALE: Experimental research has shown that 3,4-methylenedioxymethamphetamine
      (MDMA) can improve some psychomotor driving skills when administered during the
      day. In real life, however, MDMA is taken during the night, and driving may
      likely occur early in the morning after a night of "raving" and sleep loss.
      OBJECTIVES: The present study assessed the effects of MDMA on road-tracking and
      car-following performance in on-the-road driving tests in normal traffic.
      METHODS: Sixteen recreational MDMA users participated in a randomized double
      blind placebo-controlled four-way cross-over design. They received single,
      evening doses of 0, 25, 50, and 100 mg MDMA on separate occasions. Actual driving
      tests were conducted in the evening when MDMA serum concentrations were maximal
      and in the morning after a night of sleep loss. RESULTS: The primary measure of
      driving, i.e., standard deviation of lateral position (SDLP, a measure of
      weaving) was significantly increased during driving tests in the morning in all
      treatment conditions, irrespective of MDMA dose and concentration. The increments
      in SDLP were of high clinical relevance and comparable to those observed for
      alcohol at blood alcohol concentrations >0.8 mg/mL. These impairments were
      primarily caused by sleep loss. CONCLUSIONS: In general, MDMA did not affect
      driving performance nor did it change the impairing effects of sleep loss. It is
      concluded that MDMA cannot compensate for the impairing effects of sleep loss and
      that drivers who are under the influence of MDMA and sleep deprived are unfit to
      drive.

PMID- 21952669
TI  - Binge drinking differentially affects adolescent male and female brain
      morphometry.
AB  - RATIONALE: Adolescent binge drinking is concerning, as important
      neurodevelopments occur during this stage. Previous research suggests that binge
      drinking may disrupt typical brain development, and females may be particularly
      vulnerable. OBJECTIVES: We used magnetic resonance imaging (MRI) to examine
      cortical thickness in adolescent females and males with and without histories of
      binge drinking. METHODS: Participants (N = 59) were 16-19-year-old adolescents
      recruited from local schools. Recent binge drinkers (n = 29, 48% female) were
      matched to non-drinkers (n = 30, 50% female) on age, gender, pubertal
      development, and familial alcoholism. Participants completed a neuropsychological
      battery and MRI session. Cortical surfaces were reconstructed with FreeSurfer.
      RESULTS: Binge * gender interactions (p < .05) were seen for cortical thickness
      in four left frontal regions: frontal pole, pars orbitalis, medial orbital
      frontal, and rostral anterior cingulate. For all interactions, female bingers had
      thicker cortices than female controls, while male bingers had thinner cortices
      than male controls. Thicker left frontal cortices corresponded with poorer
      visuospatial, inhibition, and attention performances for female bingers (r = 
      0.69 to 0.50, p < 0.05) and worse attention for male bingers (r = -0.69, p =
      0.005). CONCLUSIONS: Adolescent females with recent binge drinking showed ~8%
      thicker cortices in left frontal regions than demographically similar female non
      drinkers, which was linked to worse visuospatial, inhibition, and attention
      performances. In contrast, adolescent binge-drinking males showed ~7% thinner
      cortices in these areas than non-drinking males. These cross-sectional data
      suggest either different gray matter risk factors for males as for females toward
      developing heavy drinking, or differential adverse sequelae.

PMID- 21952670
TI  - Opposing efficacy of group III mGlu receptor activators, LSP1-2111 and AMN082, in
      animal models of positive symptoms of schizophrenia.
AB  - RATIONALE: Several studies have suggested that modulation of the glutamatergic
      system via metabotropic glutamate receptors (mGlu) could be a new and efficient
      way to achieve antipsychotic-like activity. OBJECTIVES: Here, we decided to
      investigate the possible role of the group III mGlu receptor ligands, LSP1-2111,
      the group III mGlu receptor orthosteric agonist, preferentially stimulating mGlu4
      receptors especially in low doses, and AMN082, the mGlu7 receptor positive
      modulator. We used MK-801- and amphetamine-induced hyperactivity tests, as well
      as DOI-induced head twitches in mice as models for positive symptoms of
      psychosis. The C57Bl/6J mGlu7 receptor knockout mice were used to confirm that
      AMN082-induced effect was receptor specific. A non-selective antagonist of the
      group II/III mGlu receptors, LY341495, was used to block LSP1-2111-induced
      effects. RESULTS: LSP1-2111 (1, 2, and 5 mg kg(-1)) dose dependently inhibited
      both MK-801- and amphetamine-induced hyperactivities. Moreover, the drug
      antagonized DOI-induced head twitches. The effects of the drug were antagonized
      by LY341495 administration (1.5 mg kg(-1), i.p.). In contrast, AMN082 (3 and 6 mg
      kg(-1)) had no effect on amphetamine-induced hyperactivity but induced an
      enhancement of MK-801-induced hyperactivity and DOI-induced head twitches in
      mice. In C57Bl/6J mGlu7 receptor knockout animals (KO), those effects of AMN082
      were not observed. Moreover, mGlu7 KO animals were less sensitive for DOI-induced
      effect than their wild type littermates. CONCLUSIONS: Altogether, we propose that
      among group III mGlu receptors, mGlu4 receptor may be a promising target for the
      development of novel antipsychotic drugs.

PMID- 21952671
TI  - Delay and probability discounting in pathological gamblers with and without a
      history of substance use problems.
AB  - RATIONALE: Pathological gambling and substance use disorders are highly comorbid,
      possibly because they both stem from a similar process-impulsivity. Although much
      data exist regarding the association between delay discounting and these
      psychiatric disorders, relatively little research has examined probability
      discounting and its relationship with either substance use or gambling.
      OBJECTIVES: The goal of the current study was to compare rates of probability and
      delay discounting in a large population of pathological gamblers with and without
      a history of substance use problems. METHODS: Treatment-seeking pathological
      gamblers with (n = 117) and without (n = 119) a history of substance use problems
      completed questionnaires about discounting of hypothetical monetary outcomes and
      the Eysenck Impulsivity Questionnaire. The delay-discounting questionnaire
      involved choices between a smaller amount of money delivered immediately versus a
      larger amount delivered later, and the probability questionnaire was comprised of
      choices between a smaller certain versus a larger probabilistic monetary outcome.
      Hyperbolic functions estimated delay and probability discounting rates based on
      the indifference points obtained through the questionnaires. RESULTS: Results
      revealed significant effects of substance use problem status on delay but not on
      probability discounting, with no significant correlation noted between the two
      discounting processes. Only delay discounting correlated with Eysenck impulsivity
      scores. CONCLUSIONS: These data suggest that delay and probability discounting
      tap different dimensions, and delay discounting is more closely linked with
      substance use problem histories in pathological gamblers.

PMID- 21952672
TI  - Effect of craving induction on inhibitory control in opiate dependence.
AB  - RATIONALE: Current neurobiological models of addiction posit that drug seeking is
      much more likely to occur during emotionally charged states (such as craving), as
      deficits in inhibitory control become more pronounced during heightened
      motivational states. OBJECTIVE: The purpose of this study was to examine the
      effect of cue-induced craving states on attention and inhibitory control within
      addicted individuals. METHODS: We tested the performance of 39 opiate-dependent
      individuals on cognitive measures of attention (Digit Span, Digit Symbol, and
      Telephone Search) and inhibitory control (Counting Stroop and Go-No-Go) both
      before and after exposure to an autobiographical craving script. A non-drug using
      healthy control group (n = 19) performed the same tasks before and after
      listening to a relaxation tape. RESULTS: Following craving induction, opiate
      dependent individuals demonstrated improved performance on tests of processing
      speed and attentional span (consistent with the practice effect observed in
      controls) and increased their response errors on the Stroop task (in contrast to
      controls), while selective attention was unaffected. Individual differences in
      compulsivity mediated the association between craving and Stroop performance,
      such that low-compulsive (but not high-compulsive) individuals committed more
      response errors after craving induction. CONCLUSIONS: These findings challenge
      the notion of cue-induced craving as a primary trigger of disrupted cognition and
      drug-seeking behavior in addicted individuals, and raise the need to explore
      individual differences in compulsivity when addressing the links between craving
      and loss of control within research and clinical settings.

PMID- 21952673
TI  - Synthesis of uronic-noeurostegine--a potent bacterial beta-glucuronidase
      inhibitor.
AB  - Inhibition of beta-glucuronidases has recently been shown to be useful in
      alleviating drug toxicity for common colon cancer chemotherapeutic CPT-11 (also
      called Irinotecan). We have prepared a new compound of the nortropane-type,
      uronic-Noeurostegine, and demonstrated that this is a competitive and potent E.
      coli beta-glucuronidase inhibitor, while inhibition of the mammalian beta
      glucuronidase from bovine liver was found to be less significant. Although not
      intended, two other compounds having N-ethyl and N-(4-hydroxybutyl) substituents
      were also prepared in this study due to the sluggish debenzylation in the final
      step. The N-substituents are believed to come from reaction with the solvents
      used being ethanol and THF, respectively. These compounds also inhibited the two
      beta-glucuronidases albeit to a lesser extent compared to the parent compound.
      Noeurostegine and the three uronic-noeurostegines were additionally evaluated as
      inhibitors against a wide panel of glycosidases with the former showing potent
      inhibition of rat intestinal lactase and trehalase, whereas the latter was found
      to be inactive.

PMID- 21952674
TI  - Bluish pigmentation of the gingiva in a homeless patient: a quiz. Burton's line
      revealing chronic lead poisoning (plumbism).

PMID- 21952675
TI  - Exploring the spectral enantiodiscrimination potential of a DNA-based orienting
      medium using deuterium NMR spectroscopy.
AB  - (2)H-{(1)H} 1D and 2D-NMR spectroscopy is used to evaluate the
      enantiodiscrimination potential of DNA-based, lyotropic chiral mesophases on a
      series of (pro)chiral amino acids.

PMID- 21952676
TI  - Optical pulse-shaping for internal cooling of molecules.
AB  - We consider the use of pulse-shaped broadband femtosecond lasers to optically
      cool rotational and vibrational degrees of freedom of molecules. Since this
      approach relies on cooling rotational and vibrational quanta by exciting an
      electronic transition, it is most easily applicable to molecules with similar
      ground and excited potential energy surfaces, such that the vibrational state is
      usually unchanged during electronic relaxation. Compared with schemes that cool
      rotations by exciting vibrations, this approach achieves internal cooling on the
      orders-of-magnitude faster electronic decay timescale and is potentially
      applicable to apolar molecules. For AlH(+), a candidate species, a rate-equation
      simulation indicates that rovibrational equilibrium should be achievable in 8
      MUs. In addition, we report laboratory demonstration of optical pulse shaping
      with sufficient resolution and power for rotational cooling of AlH(+).

PMID- 21952677
TI  - Neuroendocrine interactions in the thymus: from physiology to therapy.

PMID- 21952678
TI  - Evidence of conserved neuroendocrine interactions in the thymus: intrathymic
      expression of neuropeptides in mammalian and non-mammalian vertebrates.
AB  - The function of lymphoid organs and immune cells is often modulated by hormones,
      steroids and neuropeptides produced by the neuroendocrine and immune systems. The
      thymus intrinsically produces these factors and a comparative analysis of the
      expression of neuropeptides in the thymus of different species would highlight
      the evolutionary importance of neuroendocrine interaction in T cell development.
      In this review, we highlight the evidence which describes the intrathymic
      expression and function of various neuropeptides and their receptors, in
      particular somatostatin, substance P, vasointestinal polypeptide, calcitonin gene
      related peptide and neuropeptide Y, in mammals (human, rodent) and non-mammals
      (avian, amphibian and teleost), and conclude that neuropeptides play a conserved
      role in vertebrate thymocyte development.

PMID- 21952679
TI  - Eph/Ephrin-mediated interactions in the thymus.
AB  - In the present study, we review available information on the relevance of Eph and
      ephrins in numerous processes occurring in the thymus that regulate not only T
      cell differentiation but also thymic epithelial cell (TEC) development and
      organization. Eph/ephrins are a large family of receptors and ligands involved in
      organogenesis and homeostasis of adult tissues. They are extensively expressed in
      the thymus and seem to be involved in the colonization of lymphoid progenitor
      cells and their migration throughout the thymic parenchyma necessary to provide
      an adequate topological location of developing thymocytes in the epithelial
      network that ensures their correct differentiation. In addition, EphB2 and EphB3
      play a cell-autonomous role in regulating the transitions of double-negative to
      double-positive cells and of double-positive to single-positive thymocytes and
      the lack of these molecules or their ligands ephrin B1 and ephrin B2 induces
      profound alterations of the TEC maturation and in the arrangement of epithelial
      network. We emphasize that these results are largely reflecting the role played
      by this family of molecules in controlling thymocyte-TEC interactions within the
      thymus.

PMID- 21952680
TI  - Thymic involution: where endocrinology meets immunology.
AB  - The decline in immune function with aging represents a major clinical challenge
      in many disease conditions. It is manifest in many parameters but is essentially
      linked to the adaptive immune responses. The prediction would be that
      abnormalities in both T and B lymphocytes underlie the loss of cellular and
      humoral capacity, respectively. Somewhat surprisingly, this is not reflected in
      numerical losses but more in alterations at the population and single cell
      levels. There is a major reduction in naive T cells with a proportional increase
      in memory cells, and also a generally reduced function of these cells. While bone
      marrow function reduces with age, the most obvious reason for the T cell defects
      is the severe atrophy of the thymus. This is closely aligned with puberty,
      thereby implicating a major aetiological role for sex steroids in both thymus and
      immune system deterioration with age. Accordingly surgical or chemical castration
      (utilizing luteinizing hormone-releasing hormone) blocks sex steroids resulting
      in profound rejuvenation of the immune system.

PMID- 21952681
TI  - Age-associated remodeling of neural and nonneural thymic catecholaminergic
      network affects thymopoietic productivity.
AB  - Ageing is associated with a progressive decline in thymic cytoarchitecture
      followed by a less efficient T cell development and decreased emigration of naive
      T cells to the periphery. These thymic changes are linked to increased morbidity
      and mortality from infectious, malignant and autoimmune diseases in old age.
      Therefore, it is of paramount importance to understand the thymic homeostatic
      processes across the life span, as well as to identify factors and elucidate
      mechanisms driving or contributing to the thymic involution. Catecholamines (CAs)
      derived from sympathetic nerves and produced locally by thymic cells represent an
      important component of the thymic microenvironment. In young rats, they provide a
      subtle tonic suppressive influence on T cell development acting via beta(2)- and
      alpha(1)-adrenoceptors (ARs) expressed on thymic nonlymphoid cells and
      thymocytes. In the face of thymic involution, a progressive increase in the
      thymic noradrenaline level, reflecting a rise in the density of noradrenergic
      nerve fibers and CA-synthesizing cells, occurs. In addition, the density of
      beta(2)- and alpha(1)-AR-expressing thymic nonlymphoid cells and the alpha(1)-AR
      thymocyte surface density also exhibit a pronounced increase with age. The data
      obtained from studies investigating effects of AR blockade on T cell development
      indicated that age-related changes in CA-mediated thymic communications,
      certainly those involving alpha(1)-ARs, may contribute to diminished thymopoietic
      efficiency in the elderly. Having in mind thymic plasticity in the course of
      ageing, and broadening possibilities for pharmacological modulation of CA
      signaling, we here present and discuss the progress in research related to a role
      of CAs in thymic homeostasis and age-related decay in the thymic naive T cell
      output.

PMID- 21952682
TI  - Growth hormone is a modulator of lymphocyte migration.
AB  - Cell migration is crucial for intrathymic T cell differentiation and export of
      mature T lymphocytes to the peripheral lymphoid organs. The intrinsic regulation
      of T cell migration, mediated by adhesion molecules and chemokines, can be
      influenced by a number of endogenous factors, such as hormones, as for instance
      growth hormone (GH). Laminin deposition was enhanced in GH-treated mice and in GH
      transgenic animals, compared with corresponding controls, and thymocyte adhesion
      to laminin was increased by in vivo GH treatment. An enhancing effect was also
      observed ex vivo in relation to the number of migrating cells in laminin-coated
      transwell chambers. Additionally, we found that the chemokine CXCL12, in
      conjunction with laminin, further enhanced the migration of thymocytes previously
      exposed to high concentrations of GH in vivo. Moreover, an increase in CXCL12
      production has been detected in the thymus of GH-transgenic mice as well as in
      primary thymic epithelial cell cultures derived from these animals, as compared
      to age-matched wild-type counterparts. In keeping with these data, in vivo
      experiments showed that GH favors the trafficking of naive CD4+CD8- recent thymic
      emigrants to the peripheral lymph nodes. In addition, we found that migration of
      lymphocytes from mesenteric lymph nodes of GH-transgenic mice, triggered by the
      chemokine CXCL12, in conjunction with laminin or fibronectin, was enhanced, when
      compared to lymphocytes from control mice. Since GH-based therapy has been used
      in human and experimental infectious diseases, this hormone can be envisioned as
      an additional therapeutic tool in situations in which increasing lymphocyte
      numbers and migration are required for correcting a given pathological state.

PMID- 21952683
TI  - The role of the thymus in the integrated evolution of the recombinase-dependent
      adaptive immune response and the neuroendocrine system.
AB  - Before being able to react against infectious non-self-antigens, the immune
      system has to be educated in recognition and tolerance of neuroendocrine self
      proteins. This sophisticated educational process takes place only in the thymus.
      The development of an autoimmune response directed to neuroendocrine glands has
      been shown to result from a thymus dysfunction in programming immunological self
      tolerance to neuroendocrine-related antigens. This thymus dysfunction leads to a
      breakdown of immune homeostasis with an enrichment of 'forbidden' self-reactive T
      cells and a deficiency in self-antigen-specific natural regulatory T cells in the
      peripheral T lymphocyte repertoire. A large number of neuroendocrine self
      antigens are expressed by the thymic epithelium, under the control of the
      autoimmune regulator (AIRE) gene/protein in the medulla. Based on the close
      homology and cross-tolerance between thymic type 1 diabetes-related self-antigens
      and peripheral antigens targeted in beta-cells by autoimmunity, a novel type of
      vaccination is currently developed for the prevention and cure of type 1
      diabetes. If this approach were found to be effective in reprogramming
      immunological tolerance that is absent or broken in this disease, it could pave
      the way for the design of negative/tolerogenic self-vaccines against other
      endocrine and organ-specific autoimmune disorders.

PMID- 21952684
TI  - Intercommunication between the neuroendocrine and immune systems: focus on
      myasthenia gravis.
AB  - Crosstalk exists between the nervous, endocrine, and immune systems, and
      perturbations in these interactions have been associated with disease. This
      includes production of neuroendocrine factors that alter immune system activity
      and increase susceptibility to or severity of immune-related conditions, such as
      myasthenia gravis (MG)--a T-cell-dependent, B-cell-mediated autoimmune disorder.
      MG results from impairment of transmission to the neuromuscular junction and
      involves the thymus--especially in early-onset disease, but the exact mechanism
      by which the thymus impacts disease is unclear. MG afflicts millions of
      individuals worldwide each year, and both men and women can develop symptoms.
      However, prevalence and age of onset differs between men and women. Women exhibit
      higher incidence and earlier age of onset compared to men, and disease fluctuates
      during pregnancy. This suggests that sex hormones play a role in influencing
      disease outcome. In this review, we will consider what is known about the
      manifestation of MG, theories on how different forms of MG are influenced or
      alleviated by steroid hormones, current treatment options, and what measures
      could be important to consider in the future.

PMID- 21952685
TI  - Immunoendocrinology of the thymus in Chagas disease.
AB  - During immune response to infectious agents, the host develops an inflammatory
      response which could fail to eliminate the pathogen or may become dysregulated.
      In this case, the ongoing response acquires a new status and turns out to be
      detrimental. The same elements taking part in the establishment and regulation of
      the inflammatory response (cytokines, chemokines, regulatory T cells and
      counteracting compounds like glucocorticoids) may also mediate harmful effects.
      Thymic disturbances seen during Trypanosoma cruzi (T. cruzi) infection fit well
      with this conceptual framework. After infection, this organ suffers a severe
      atrophy due to apoptosis-induced thymocyte exhaustion, mainly affecting the
      immature double-positive (DP) CD4+CD8+ population. Thymus cellularity depletion,
      which occurs in the absence of main immunological mediators involved in anti-T.
      cruzi defense, seems to be linked to a systemic cytokine/hormonal imbalance,
      involving a dysregulated increase in Tumor Necrosis Factor alpha (TNF-alpha) and
      corticosterone hormone levels. Additionally, we have found an anomalous exit of
      potentially autoimmune DP cells to the periphery, in parallel to a shrinkage in
      the compartment of natural regulatory T cells. In this context, our data clearly
      point to the view that the thymus is a target organ of T. cruzi infection.
      Preserved thymus may be essential for the development of an effective immune
      response against T. cruzi, but this organ is severely affected by a dysregulated
      circuit of proinflammatory cytokines and glucocorticoids. Also, the alterations
      observed in the DP population might have potential implications for the
      autoimmune component of human Chagas disease.

PMID- 21952686
TI  - The role of the sympathetic nervous system in the thymus in health and disease.
AB  - The existence of a network of immunoneuroendocrine interactions that results in
      the reciprocal modulation of the classical functions of each system is well
      established at present. Most of the evidence derives from studies on secondary
      lymphoid organs, such as the spleen and lymph nodes. In this article, several
      aspects relevant to understand the role of the sympathetic nervous system in the
      establishment of these interactions in the thymus are discussed. At present, the
      sympathetic innervation of the thymus, the expression of adrenergic receptors in
      thymic cells, particularly of beta-adrenergic receptors, and the effect of
      sympathetic neurotransmitters, although mainly derived from in vitro or
      pharmacological studies, seem to be relatively well studied. However, other
      aspects, such as the relevance that immune-sympathetic interactions at the thymic
      level may have for certain diseases, specially autoimmune or other diseases that
      primarily involve the activation of the immune system, as well as how the
      integration of sympathetic and hormonal signals at local levels may affect thymic
      functions, certainly deserve further investigation.

PMID- 21952687
TI  - Thymulin-based gene therapy and pituitary function in animal models of aging.
AB  - Thymulin is a thymic hormone exclusively produced by the thymic epithelial cells.
      After its discovery and initial characterization in the 1970s, it was
      demonstrated that thymulin production and secretion is strongly influenced by the
      neuroendocrine system. Conversely, a growing core of information, to be reviewed
      here, points to thymulin as a hypophysiotropic peptide. Additionally, thymulin
      was shown to possess anti-inflammatory and analgesic properties in the brain. In
      recent years, a synthetic DNA sequence coding for a biologically active analog of
      thymulin, metFTS, was constructed and cloned in different adenoviral vectors.
      These include bidirectional regulatable Tet-Off vector systems that
      simultaneously express metFTS and green fluorescent protein and that can be
      downregulated reversibly by the addition of the antibiotic doxycycline. A number
      of recent studies suggest that thymulin gene therapy may be a suitable
      therapeutic strategy to prevent some of the endocrine and reproductive
      alterations that typically appear in congenitally athymic (nude) mice, taken as a
      suitable model of neuroendocrine and reproductive aging. The present article
      briefly reviews the literature on the physiology of the thymulin-pituitary axis
      as well as on the new molecular tools available to exploit the therapeutic
      potential of thymulin.

PMID- 21952688
TI  - The relationship between immediate relevant basic science knowledge and clinical
      knowledge: physiology knowledge and transthoracic echocardiography image
      interpretation.
AB  - Two major views on the relationship between basic science knowledge and clinical
      knowledge stand out; the Two-world view seeing basic science and clinical science
      as two separate knowledge bases and the encapsulated knowledge view stating that
      basic science knowledge plays an overt role being encapsulated in the clinical
      knowledge. However, resent research has implied that a more complex relationship
      between the two knowledge bases exists. In this study, we explore the
      relationship between immediate relevant basic science (physiology) and clinical
      knowledge within a specific domain of medicine (echocardiography). Twenty eight
      medical students in their 3rd year and 45 physicians (15 interns, 15 cardiology
      residents and 15 cardiology consultants) took a multiple-choice test of
      physiology knowledge. The physicians also viewed images of a transthoracic
      echocardiography (TTE) examination and completed a checklist of possible
      pathologies found. A total score for each participant was calculated for the
      physiology test, and for all physicians also for the TTE checklist. Consultants
      scored significantly higher on the physiology test than did medical students and
      interns. A significant correlation between physiology test scores and TTE
      checklist scores was found for the cardiology residents only. Basic science
      knowledge of immediate relevance for daily clinical work expands with increased
      work experience within a specific domain. Consultants showed no relationship
      between physiology knowledge and TTE interpretation indicating that experts do
      not use basic science knowledge in routine daily practice, but knowledge of
      immediate relevance remains ready for use.

PMID- 21952689
TI  - Acute myeloid leukemia unlikely related to trabectedin treatment.

PMID- 21952690
TI  - A maternal erythrocyte DHA content of approximately 6 g% is the DHA status at
      which intrauterine DHA biomagnifications turns into bioattenuation and postnatal
      infant DHA equilibrium is reached.
AB  - PURPOSE: Higher long-chain polyunsaturated fatty acids (LCP) in infant compared
      with maternal lipids at delivery is named biomagnification. The decline of infant
      and maternal docosahexaenoic acid (DHA) status during lactation in Western
      countries suggests maternal depletion. We investigated whether biomagnification
      persists at lifelong high fish intakes and whether the latter prevents a
      postpartum decline of infant and/or maternal DHA status. METHODS: We studied 3
      Tanzanian tribes with low (Maasai: 0/week), intermediate (Pare: 2-3/week), and
      high (Sengerema: 4-5/week) fish intakes. DHA and arachidonic acid (AA) were
      determined in maternal (m) and infant (i) erythrocytes (RBC) during pregnancy
      (1st trimester n = 14, 2nd = 103, 3rd = 88), and in mother-infant pairs at
      delivery (n = 63) and at 3 months postpartum (n = 104). RESULTS: At delivery,
      infants of all tribes had similar iRBC-AA which was higher than, and unrelated
      to, mRBC-AA. Transplacental DHA biomagnification occurred up to 5.6 g% mRBC-DHA;
      higher mRBC-DHA was associated with "bioattenuation" (i.e., iRBC-DHA < mRBC-DHA).
      Compared to delivery, mRBC-AA after 3 months was higher, while iRBC-AA was lower.
      mRBC-DHA after 3 months was lower, while iRBC-DHA was lower (low fish intake),
      equal (intermediate fish intake), and higher (high fish intake) compared to
      delivery. We estimated that postpartum iRBC-DHA equilibrium is reached at 5.9 g%,
      which corresponds to a mRBC-DHA of 6.1 g% throughout pregnancy. CONCLUSION:
      Uniform high iRBC-AA at delivery might indicate the importance of intrauterine
      infant AA status. Biomagnification reflects low maternal DHA status, and
      bioattenuation may prevent intrauterine competition of DHA with AA. A mRBC-DHA of
      about 6 g% during pregnancy predicts maternal-fetal equilibrium at delivery,
      postnatal iRBC-DHA equilibrium, but is unable to prevent a postnatal mRBC-DHA
      decline.

PMID- 21952691
TI  - High-level dietary fibre up-regulates colonic fermentation and relative abundance
      of saccharolytic bacteria within the human faecal microbiota in vitro.
AB  - BACKGROUND: Health authorities around the world advise citizens to increase their
      intake of foods rich in dietary fibre because of its inverse association with
      chronic disease. However, a few studies have measured the impact of increasing
      mixed dietary fibres directly on the composition of the human gut microbiota.
      AIMS OF THE STUDY: We studied the impact of high-level mixed dietary fibre intake
      on the human faecal microbiota using an in vitro three-stage colonic model.
      METHODS: The colonic model was maintained on three levels of fibre, a basal level
      of dietary fibre, typical of a Western-style diet, a threefold increased level
      and back to normal level. Bacterial profiles and short chain fatty acids
      concentrations were measured. RESULTS: High-level dietary fibre treatment
      significantly stimulated the growth of Bifidobacterium, Lactobacillus
      Enterococcus group, and Ruminococcus group (p < 0.05) and significantly increased
      clostridial cluster XIVa and Faecalibacterium prausnitzii in vessel 1 mimicking
      the proximal colon (p < 0.05). Total short chain fatty acids concentrations
      increased significantly upon increased fibre fermentation, with acetate and
      butyrate increasing significantly in vessel 1 only (p < 0.05). Bacterial species
      richness changed upon increased fibre supplementation. The microbial community
      and fermentation output returned to initial levels once supplementation with high
      fibre ceased. CONCLUSIONS: This study shows that high-level mixed dietary fibre
      intake can up-regulate both colonic fermentation and the relative abundance of
      saccharolytic bacteria within the human colonic microbiota. Considering the
      important role of short chain fatty acids in regulating human energy metabolism,
      this study has implications for the health-promoting potential of foods rich in
      dietary fibres.

PMID- 21952693
TI  - Effect of soy and milk protein supplementation on serum lipid levels: a
      randomized controlled trial.
AB  - BACKGROUND/OBJECTIVE: Previous clinical trials have documented that soy protein
      reduces low-density lipoprotein cholesterol and increases high-density
      lipoprotein (HDL) cholesterol compared with milk protein. However, the effect of
      soy protein on lipids compared with carbohydrate has not been not well studied.
      We examined the effect of soy and milk protein supplementation on lipids and
      lipoproteins compared with carbohydrate among adults without
      hypercholesterolemia. SUBJECTS/METHODS: We conducted a randomized, double-blind,
      3-phase crossover trial among 352 US adults with serum total cholesterol level of
      <240 mg/dl from September 2003 to April 2008. Trial participants were assigned to
      40 g/day supplementation of soy protein, milk protein or complex carbohydrate
      from wheat each for 8 weeks in random order with a 3-week washout period between
      interventions. Overnight fasting blood samples were collected at the termination
      of each intervention phase. RESULTS: Compared with carbohydrate, soy protein
      supplementation was significantly associated with a net change (95% confidence
      interval (CI)) in total cholesterol and total/HDL cholesterol ratio of -3.97
      mg/dl (-7.63 to -0.31, P=0.03) and -0.12 (-0.23 to -0.01, P=0.03), respectively.
      Compared with milk protein, soy protein supplementation was significantly
      associated with a net change (95% CI) in HDL and total/HDL cholesterol ratio of
      1.54 mg/dl (0.63 to 2.44, P=0.0009) and -0.14 (-0.22 to -0.05, P=0.001),
      respectively. Compared with carbohydrate, milk protein supplementation was
      significantly associated with a net change (95% CI) in HDL of -1.13 mg/dl (-2.05
      to -0.22, P=0.02). CONCLUSIONS: This randomized controlled trial indicates that
      soy protein, but not milk protein, supplementation improves the lipid profile
      among healthy individuals.

PMID- 21952692
TI  - Consumption of fructose-sweetened beverages for 10 weeks reduces net fat
      oxidation and energy expenditure in overweight/obese men and women.
AB  - BACKGROUND/OBJECTIVES: The results of short-term studies in humans suggest that,
      compared with glucose, acute consumption of fructose leads to increased
      postprandial energy expenditure and carbohydrate oxidation and decreased
      postprandial fat oxidation. The objective of this study was to determine the
      potential effects of increased fructose consumption compared with isocaloric
      glucose consumption on substrate utilization and energy expenditure following
      sustained consumption and under energy-balanced conditions. SUBJECTS/METHODS: As
      part of a parallel arm study, overweight/obese male and female subjects, 40-72
      years, consumed glucose- or fructose-sweetened beverages providing 25% of energy
      requirements for 10 weeks. Energy expenditure and substrate utilization were
      assessed using indirect calorimetry at baseline and during the 10th week of
      intervention. RESULTS: Consumption of fructose, but not glucose, led to
      significant decreases of net postprandial fat oxidation and significant increases
      of net postprandial carbohydrate oxidation (P<0.0001 for both). Resting energy
      expenditure (REE) decreased significantly from baseline values in subjects
      consuming fructose (P=0.031) but not in those consuming glucose. CONCLUSIONS:
      Increased consumption of fructose for 10 weeks leads to marked changes of
      postprandial substrate utilization including a significant reduction of net fat
      oxidation. In addition, we report that REE is reduced compared with baseline
      values in subjects consuming fructose-sweetened beverages for 10 weeks.

PMID- 21952694
TI  - Associations between mothers' perceptions of the cost of fruit and vegetables and
      children's diets: will children pay the price?
AB  - BACKGROUND/OBJECTIVES: Perceptions that fruit and vegetables are expensive are
      more common among the socio-economically disadvantaged groups and are linked to
      poor dietary outcomes. Such perceptions may be exacerbated in countries recently
      affected by natural disasters, where devastation of fruit and vegetable crops has
      resulted in increase in prices of fruit and vegetables. Examining the
      associations of perceptions of fruit and vegetable affordability and children's
      diets can offer insights into how the high prices of fruit and vegetables might
      have an impact on the diets of children. SUBJECTS/METHODS: We analysed the data
      from 546 socio-economically disadvantaged mother-child pairs to assess the
      relationship between maternal perceptions of fruit and vegetable affordability
      and the diets of their children. RESULTS: Fruit consumption was lower among
      children whose mothers felt the cost of fruit was too high. Maternal perceptions
      of fruit and vegetable affordability were not associated with any other aspect of
      child's diet. CONCLUSIONS: Our results suggest a possible role for maternal
      perceptions of fruit affordability in children's diet, though further research is
      warranted.

PMID- 21952696
TI  - The association between inflammatory biomarkers and metabolically healthy obesity
      depends of the definition used.
AB  - BACKGROUND/OBJECTIVES: To assess the distribution of interleukin (IL)-1beta, IL
      6, tumour necrosis factor (TNF)-alpha and C-reactive protein (CRP) according to
      the different definitions of metabolically healthy obesity (MHO).
      SUBJECTS/METHODS: A total of 881 obese (body mass index (BMI) > or =30 kg/m2)
      subjects derived from the population-based CoLaus Study participated in this
      study. MHO was defined using six sets of criteria including different
      combinations of waist, blood pressure, total high-density lipoprotein cholesterol
      or low-density lipoprotein -cholesterol, triglycerides, fasting glucose,
      homeostasis model, high-sensitivity CRP, and personal history of cardiovascular,
      respiratory or metabolic diseases. IL-1beta, IL-6 and TNF-alpha were assessed by
      multiplexed flow cytometric assay. CRP was assessed by immunoassay. RESULTS: On
      bivariate analysis some, but not all, definitions of MHO led to significantly
      lower levels of IL-6, TNF-alpha and CRP compared with non-MH obese subjects. Most
      of these differences became nonsignificant after multivariate analysis. An
      posteriori analysis showed a statistical power between 9 and 79%, depending on
      the inflammatory biomarker and MHO definition considered. Further increasing
      sample size to overweight+obese individuals (BMI > or =25 kg/m2, n=2917) showed
      metabolically healthy status to be significantly associated with lower levels of
      CRP, while no association was found for IL-1beta. Significantly lower IL-6 and
      TNF-alpha levels were also found with some but not all MHO definitions, the
      differences in IL-6 becoming nonsignificant after adjusting for abdominal obesity
      or percent body fat. CONCLUSIONS: MHO individuals present with decreased levels
      of CRP and, depending on MHO definition, also with decreased levels in IL-6 and
      TNF-alpha. Conversely, no association with IL-1beta levels was found.

PMID- 21952697
TI  - The mental development and behavior of low-birth-weight Bangladeshi infants from
      an urban low-income community.
AB  - BACKGROUND/OBJECTIVES: Adverse developmental consequences of low-birth-weight
      (LBW) infants have been frequently reported from developed countries where most
      of them are preterm. Few reports are available from developing countries, where
      the problem is huge and newborns are mostly term babies. We aimed to compare
      mental and psychomotor development and behavior of LBW Bangladeshi infants with
      those of normal-birth-weight (NBW) infants. SUBJECT/METHODS: Secondary data
      analyses from a randomized controlled trial of fish oil supplementation during
      pregnancy on infants' development at 10 month. There was no effect of
      supplementation on infants' development. All LBW (n=66) and NBW (n=183) infants
      were assessed for their mental development index (MDI), psychomotor development
      index (PDI), behavior and quality of psychosocial stimulation received at home.
      Socioeconomic information and anthropometric measurements were available, and
      bivariate and multivariate analyses were performed to examine group differences.
      RESULTS: LBW infants scored significantly lower than NBW infants on MDI, PDI,
      activity and emotional tone. They came from comparatively poorer families and had
      lower gestational age than the NBW infants. After controlling for possible
      confounders, the NBW infants had significantly higher MDI (B=2.7, s.e.=1.1, 95%
      confidence interval (CI): 0.6-4.8), PDI (B=3.5, s.e.=1.3, 95% CI: 1.0-6.0) and
      activity (B=0.5, s.e.=0.2, 95% CI: 0.1-0.9) scores. Furthermore, in a subgroup
      analyses, a consistent pattern of developmental delay was also noted in favor of
      term-LBW infants. CONCLUSIONS: In a poor-urban Bangladeshi community, LBW infants
      had significantly lower mental and psychomotor developments and were less active
      than NBW infants at 10 months of age.

PMID- 21952698
TI  - Seeing more is seeing better.

PMID- 21952695
TI  - Beverage consumption among European adolescents in the HELENA study.
AB  - BACKGROUND/OBJECTIVES: Our objective was to describe the fluid and energy
      consumption of beverages in a large sample of European adolescents.
      SUBJECTS/METHODS: We used data from 2741 European adolescents residing in 8
      countries participating in the Healthy Lifestyle in Europe by Nutrition in
      Adolescence Cross-Sectional Study (HELENA-CSS). We averaged two 24-h recalls,
      collected using the HELENA-dietary assessment tool. By gender and age subgroup
      (12.5-14.9 years and 15-17.5 years), we examined per capita and per consumer
      fluid (milliliters (ml)) and energy (kilojoules (kJ)) intake from beverages and
      percentage consuming 10 different beverage groups. RESULTS: Mean beverage
      consumption was 1611 ml/day in boys and 1316 ml/day in girls. Energy intake from
      beverages was about 1966 kJ/day and 1289 kJ/day in European boys and girls,
      respectively, with sugar-sweetened beverages (SSBs) (carbonated and non
      carbonated beverages, including soft drinks, fruit drinks and
      powders/concentrates) contributing to daily energy intake more than other groups
      of beverages. Boys and older adolescents consumed the most amount of per capita
      total energy from beverages. Among all age and gender subgroups, SSBs, sweetened
      milk (including chocolate milk and flavored yogurt drinks all with added sugar),
      low-fat milk and fruit juice provided the highest amount of per capita energy.
      Water was consumed by the largest percentage of adolescents followed by SSBs,
      fruit juice and sweetened milk. Among consumers, water provided the greatest
      fluid intake and sweetened milk accounted for the largest amount of energy intake
      followed by SSBs. Patterns of energy intake from each beverage varied between
      countries. CONCLUSIONS: European adolescents consume an average of 1455 ml/day of
      beverages, with the largest proportion of consumers and the largest fluid amount
      coming from water. Beverages provide 1609 kJ/day, of which 30.4%, 20.7% and 18.1%
      comes from SSBs, sweetened milk and fruit juice, respectively.

PMID- 21952699
TI  - A study on the diagnosis of minimal endoscopic lesions in nonerosive reflux
      esophagitis using computed virtual chromoendoscopy (FICE).
AB  - CONTEXT: Gastroesophageal reflux disease is very prevalent in the world.
      Endoscopically it can be classified as nonerosive when there is no mucosal
      erosive lesion on endoscopy. The presence of endoscopic minimal lesions is
      included in the Los Angeles classification for reflux disease. Virtual
      chromoendoscopy Fuji Intelligent Color Enhancement (FICE) is an endoscopic
      technique that enhances detection of small lesions of the digestive tract.
      OBJECTIVE: To evaluate whether the use of FICE improves the diagnosis of minimal
      lesions on endoscopy, and to assess the association of symptoms with minimal
      lesions in patients with nonerosive reflux disease. METHODS: One hundred fifty
      five patients were enrolled, 62 with typical reflux symptoms and 93 without
      esophageal symptoms. The patients had normal esophageal endoscopy or minimal
      lesions. Each patient was examined initially by conventional video endoscopy and
      then using FICE. RESULTS: Among 155 patients, 113 had a normal conventional
      endoscopy and 42 had minimal lesions. Sixty-two patients had typical reflux
      symptoms, and 93 other symptoms unrelated to reflux. In 104 patients, the
      esophageal mucosa was normal for both conventional endoscopy and FICE, in 42
      patients both techniques showed minimal lesions, in 9 patients conventional
      endoscopy was normal and minimal lesions were shown by FICE. The height and
      circumference of minimal lesions were greater using FICE than that measured by
      conventional endoscopy. There was a significant association of the presence of
      minimal lesions with male gender, but not with alcoholism, smoking, anti
      inflammatory drugs and age. The diagnosis of minimal lesions was observer
      dependent, both in conventional endoscopy as using FICE. CONCLUSIONS: The use of
      FICE improves the diagnosis of minimal lesions as compared to conventional
      videoendoscopy, although this diagnosis remains observer-dependent. There was no
      association between the presences of minimal lesions with reflux symptoms.

PMID- 21952700
TI  - High prevalence of duodenal ulcer in a tertiary care hospital in the city of Sao
      Paulo, SP, Brazil.
AB  - CONTEXT: In spite of Helicobacter pylori infection being the etiological cause of
      peptic ulcer and its high prevalence in Brazil, the prevalence of peptic ulcer
      disease has been poorly studied. OBJECTIVES: To verify the peptic ulcer disease
      prevalence in patients of a tertiary care hospital. METHODS: Diagnostic findings
      from 1,478 consecutive endoscopies were correlated with the urease test results
      for H. pylori infection diagnosis and demographic data in a total of 3,779
      endoscopies performed in 2005. The mean age of the patients was 51.14 +/- 16.46,
      being 613 (41.5%) men. RESULTS: Peptic ulcer was diagnosed in 494 (33.4%)
      patients with a mean age of 54.86 +/- 14.53, 205 (52%) were men, being 391
      (26.5%) duodenal ulcer and 103 (7%) gastric ulcer. Normal endoscopy was found in
      272 (18.4%) patients with a mean age of 38.4 +/- 15.22, being 49 (18%) men. The
      comparison of peptic ulcer group with the patients that had normal endoscopy
      revealed that H. pylori infection [P = 0.005; OR = 1.70; 95% CI = 1.17-2.47],
      male gender [P<0.0001; OR = 5.53; 95%CI = 3.67-8.34] and older age [P<0.0001; OR
      = 1.08; 95%CI = 1.06-1.09] increased the risk of peptic ulcers. The overall H.
      pylori prevalence was 53% (786). CONCLUSIONS: Prevalence of duodenal ulcer is
      high in a Brazilian population that had H. pylori infection associated with older
      age and male gender as important determinants to gastrointestinal diseases
      outcome. Future prospective studies should confirm these findings.

PMID- 21952701
TI  - Change in platelet count in patients with hypersplenism subjected to liver
      transplantation.
AB  - CONTEXT: Most patients subjected to liver transplantation presents hypersplenism,
      which is reversed after the operation. However, some patients remain with
      moderate to intense hypersplenism. OBJECTIVES: To study the effect of liver
      transplantation on platelet count in patients with hypersplenism. METHOD: Of a
      total of 233 patients who underwent liver transplantation, 162 were excluded from
      the present study because of occurrence of steroid-resistant rejection, absence
      of hypersplenism before the transplantation, absence of follow-up for at least 2
      years or incomplete exams data. The electronic study protocols of the remaining
      71 patients were reviewed to determine the demographics, etiology of cirrhosis,
      and results of pathologic examination of the explanted liver. Serial platelet
      count was obtained from the study protocol on the day before liver
      transplantation and 1, 2, 4, and 6 months and 1 year after liver transplantation.
      Statistical analysis was performed using the Student's t-test, chi-square test,
      and Spearman's correlation test. RESULTS: Posttransplant platelet count at all
      time intervals was significantly higher than the pretransplant value (P<0.001 for
      all time intervals). Thrombocytopenia was reversed (platelet count
      >100,000/mm(3)) in 58 patients (81.7%) 1 month after liver transplantation.
      Twelve patients (16.9%) remained with thrombocytopenia 1 year after liver
      transplantation. Three patients (4.2%) had recurrence of thrombocytopenia within
      1 year after liver transplantation. There was no correlation between
      pretransplant platelet count and the Child-Pugh class or the MELD score.
      CONCLUSION: Liver transplantation reverses hypersplenism in most patients.

PMID- 21952702
TI  - Analysis of the sustained virological response in patients with chronic hepatitis
      C and liver steatosis.
AB  - CONTEXT: Chronic hepatitis C as well as non-alcoholic fatty liver disease are
      recognized as the main cause of liver disease in Western countries. It is common
      to see the concomitance of the diseases and the influence of steatosis in the
      sustained virological response of patients with hepatitis C virus. OBJECTIVE:
      Assess the sustained virological response in chronic hepatitis C patients
      according to the presence of liver steatosis. METHODS: One hundred sixty patients
      with chronic hepatitis C were retrospectively evaluated. Demographic data such as
      gender, age, body mass index, presence of diabetes mellitus and systemic arterial
      hypertension, virus genotype and use of pegylated interferon were analyzed, as
      was the staging of fibrosis and the presence of steatosis at histology. RESULTS:
      Most patients were male (57.5%), with a mean age of 48 +/- 9.7 years. The most
      frequent genotype observed was 3 (56.9%) and, in the histological evaluation,
      steatosis was observed in 65% of the patients (104/160). Sustained virological
      response in patients with steatosis occurred in 38.5%, and in 32.1% in patients
      without steatosis (P = 0.54). When we analyzed possible factors associated with
      the presence of steatosis, only body mass index and systemic arterial
      hypertension revealed a significant association. When the factors that influenced
      sustained virological response were evaluated in a logistic regression, genotype
      and use of pegylated interferon proved to be independent factors associated to
      the response. CONCLUSION: In the evaluated patients the presence of liver
      steatosis did not influence the sustained virological response of patients with
      chronic hepatitis C treated with interferon and ribavirin.

PMID- 21952703
TI  - Gluco-lipidic indices in treated hypothyroidism associated with nonalcoholic
      fatty liver disease.
AB  - CONTEXT: Thyroid hormones may interfere with regulation of lipid and carbohydrate
      metabolism as well as with severity of nonalcoholic fatty liver disease (NAFLD),
      however results are still debated. OBJECTIVES: Retrospective evaluation of
      clinical and metabolic correlations between hypothyroidism and NAFLD was the
      target. METHODS: Clinical, biochemical and histological investigation of 103
      NAFLD patients exhibiting drug-treated hypothyroidism was conducted. RESULTS:
      Steatosis was present in 32.0% of the population and nonalcoholic steatohepatitis
      in 68.0%. Females were the majority in both groups, with age of 50.0 +/- 1.5 and
      56.0 +/- 1.1 years, respectively. Hypothyroidism was not rare (15.5%), and
      multivariate analysis confirmed positive correlation with this disease for
      insulin (r = 0.213, P = 0.03), glucose homeostasis index "HOMA" (r = 0.221, P =
      0.02), aspartate aminotransferase (r = 0.234, P = 0.01) and triglycerides above
      150 mg/dL (r = 0.233, P = 0.01). No association between hypothyroidism and
      steatohepatitis could be established. CONCLUSION: A link could be identified
      between hypothyroidism and markers of glucose and lipid homeostasis, but not with
      severity of NAFLD. The lack of correlation with liver biopsy requires further
      studies.

PMID- 21952704
TI  - Comparison of three methods based on endoscopic gastric biopsies for diagnosis of
      Helicobacter pylori active infection in a clinical setting.
AB  - CONTEXT: The correct diagnosis and effective treatment of Helicobacter pylori
      gastric infection are essential in controlling this infection. OBJECTIVE: To
      compare the diagnostic value of three tests based in endoscopic gastric biopsies
      histopathological evaluation with hematoxylin-eosin (H-E) staining, urease rapid
      test and microbiological culture for detecting Helicobacter pylori active
      infection, in order to make recommendations for daily clinical practice. METHODS:
      Gastric biopsies from 115 adult patients (85 female/30 male) were obtained by
      upper gastrointestinal endoscopy and studied by histopathological evaluation with
      H-E (antrum-corpus), urease test in 2 hours (antrum) and microbiological culture
      (antrum). RESULTS: Helicobacter pylori active infection was diagnosed in 67% of
      patients. Helicobacter pylori active infection was detected by histopathological
      evaluation with H-E, urease test and microbiological culture in 87%, 79% and 70%
      of the positive cases, respectively. There were significant differences when
      histopathological evaluation with H-E and urease test rapid test when compared
      with microbiological test (P<0.01). There was no significant difference between
      histopathological evaluation with H-E and urease test (P = 0.7). The kappa index
      of agreement for histopathological evaluation with H-E/urease test was 0.56,
      histopathological evaluation with H-E/microbiological culture 0.6, and urease
      test/microbiological culture 0.64. CONCLUSIONS: In a hospital setting like the
      one studied, histopathological evaluation with H-E and urease test are the most
      recommended tests for diagnosis of Helicobacter pylori active infection based in
      endoscopic biopsies. If pathological information of gastric lesions will be
      required, histopathological evaluation with H-E is essential. Urease test is
      mandatory if a prompt diagnosis is necessary. Microbiological culture can be used
      in cases of persistent or complicated infection, which may require studies on
      Helicobacter virulence or antimicrobial susceptibility. Selected cases might
      demand a combination of several tests. The three tests exhibit a good concordance
      level for Helicobacter pylori active infection diagnosis.

PMID- 21952705
TI  - Possible interaction of gender and age on human swallowing behavior.
AB  - CONTEXT: The swallowing behavior is affected by age and possibly by gender.
      However, the interaction of the effects of age and gender on swallowing is not
      completely known. OBJECTIVES: To evaluate the possibility of interaction of
      gender and age on human swallowing behavior. METHOD: Swallowing was evaluated in
      89 healthy subjects by the water swallowing test, 43 men and 46 women aged 20-40
      years (younger, n = 38), 41-60 years (middle-aged, n = 31) and 61-80 years
      (older, n = 20). Each subject ingested in triplicate 50 mL of water while
      precisely timed and the number of swallows needed to ingest all the volume was
      counted. RESULTS: The interval between swallows was shorter and the volume in
      each swallow was smaller in women compared to men. In older subjects the time to
      ingest the 50 mL of water was longer, the interval between swallows was longer,
      and swallowing flow and volume in each swallow were smaller than in younger and
      middle-aged subjects. The swallowing flow was lower in women compared to men in
      younger subjects. The volume of each swallow was smaller in women than in men in
      younger and middle-aged subjects. There was no difference in swallowing flow and
      volume between older men and older women. CONCLUSION: Age and gender influence
      swallowing behavior, with the effect of gender being more evident in younger
      subjects and the effect of age being more evident in men.

PMID- 21952706
TI  - Adherence of enteroaggregative Escherichia coli to the ileal and colonic mucosa:
      an in vitro study utilizing the scanning electron microscopy.
AB  - CONTEXT: Enteroaggregative Escherichia coli strains have been associated with
      persistent diarrhea in several developing countries. In vivo procedures with
      animal models, in vitro assays with cellular lines and in vitro organ culture
      with intestinal fragments have been utilized to study these bacteria and their
      pathogenicity. OBJECTIVE: The present experimental research assessed the
      pathogenic interactions of three enteroaggregative Escherichia coli strains,
      using the in vitro organ culture, in order to show the adherence to different
      regions of both, the ileal and the colonic mucosa and demonstrate possible
      mechanisms that could have the participation in the prolongation of
      diarrheiogenic process. METHODS: This study used intestinal fragments from
      terminal ileum and colon that were excised from pediatric patients undergoing
      intestinal surgeries and from adult patients that underwent to colonoscopic
      procedures. Each strain was tested with three intestinal fragments for each
      region. Tissue was fixed for scanning electron microscopic analysis. RESULTS:
      These bacteria colonized ileal and colonic mucosa in the typical stacked-brick
      configuration in the ileum and colon. In both regions, the strains were seen over
      a great amount of mucus and sometimes over the intact epithelium. In some
      regions, there is a probable evidence of effacement of the microvilli. It was
      possible to see adhered to the intestinal surface, bacteria fimbrial structures
      that could be responsible for the adherence process. CONCLUSION: In order to
      cause diarrhea, enteroaggregative Escherichia coli strains adhere to the
      intestinal mucosa, create a mucoid biofilm on the small bowel surface that could
      justify the digestive-absorptive abnormalities and consequently, prolonging the
      diarrhea.

PMID- 21952707
TI  - Analysis of myosin-V immunoreactive myenteric neurons from arthritic rats.
AB  - CONTEXT: The inflammatory response itself and the consequent oxidative stress are
      able to promote neurodegeneration. So, it is possible that enteric nervous system
      is affected by inflammatory diseases threatening quality of life of patients.
      However, gastrointestinal symptoms of arthritis are usually attributed to anti
      inflammatory drugs rather than neural damage. OBJECTIVE: To confirm if the
      general population of myenteric neurons from the ileum and jejunum of rats is
      affected by arthritis. METHODS: Twenty Holtzmann rats, 58-day-old male, were used
      and divided in four groups: control group (C30), arthritic group (Art30), older
      control group (C60) and older arthritic group (Art60). At 58 days old, the
      animals in groups Art30 and Art60 received an injection of the complete Freund's
      adjuvant in order to induce arthritis. The whole-mount preparations of ileum and
      jejunum were processed for myosin-V immunohistochemistry. Quantitative and
      morphometric analyses were performed. RESULTS: Groups Art30 and Art60 presented,
      respectively, a reduction of 2% and 6% in intestinal area when compared to their
      control groups. No significant differences were observed in general neuronal
      density among the four groups (P>0.05). Group C60 presented a reduction of 14.4%
      and 10.9% in mean neuronal cell body area when compared to group C30 (P<0.05),
      for the ileum and jejunum, respectively. The other groups had a similar mean
      neuronal cell body area (P>0.05). CONCLUSION: Arthritis does not promote
      quantitative or morphological damages in general myenteric population. However,
      studies in progress have revealed some significant alterations in myenteric
      neurons subpopulations (nitrergic and VIP-ergic neurons).

PMID- 21952708
TI  - Protection of estrogen in portal hypertension gastropathy: an experimental model.
AB  - CONTEXT: Portal hypertension is a complication secondary to cirrhosis that is
      characterized by increased blood flow and/or vascular resistance in the portal
      system, causing the appearance of a hyperdynamic collateral circulation. Partial
      portal vein ligation is an experimental model used in rats to study the
      pathophysiological mechanisms involved in pre-hepatic portal hypertension.
      Estrogen E2 is an antioxidant molecule with various physiological actions.
      OBJECTIVES: To evaluate the antioxidant activity of endogenous estrogen in an
      experimental model of partial portal vein ligation by comparing intact with
      castrated rats. METHODS: Twenty Wistar rats, weighing on average 250 g were used
      and divided into four groups: sham-operated (SO); intact (I) with partial portal
      vein ligation (I + PPVL), castrated (C) and castrated with partial ligation of
      the vein (C + PPVL). Day 1: castration or sham-operation; day 7, PPVL surgery; on
      day 15 post-PPVL, portal pressure in the mesenteric vein of rats was measured on
      polygraph Letica. Lipid peroxidation in the stomach was assessed using the
      technique of thiobarbituric acid reactive substances and activity of antioxidant
      enzymes superoxide dismutase, catalase and glutathione peroxidase. Statistical
      analysis was done with ANOVA - Student-Newman-Keuls (mean +/- SE), and P<0.05 was
      considered as significant. RESULTS: Portal pressure was significantly increased
      in C + PPVL as compared to the other groups. There was no significant difference
      in the group of intact rats. TBARS showed significant damage in C and C + PPVL in
      relation to others. Antioxidant enzymes were significantly increased in the
      castrated rats with subsequent PPVL as compared to the other groups. CONCLUSION:
      We suggest that estrogen E2 plays a protective role in intact compared with
      castrated rats because it presents hydrophenolic radicals in its molecule, thus
      acting as an antioxidant in this experimental model.

PMID- 21952709
TI  - The role of hilar lymphadenectomy in patients subjected to hepatectomy due to
      colorectal metastasis.
AB  - CONTEXT: Hepatectomy is the treatment of choice for colorectal liver metastases,
      and several studies have shown good results, with 5-year survival rates ranging
      from 40% to 57%. Several clinical and pathological predictive factors for
      survival after liver resection have been studied. Involvement of the hepatic
      hilum lymph nodes, the incidence of which varies from 2% to 10%, indicates a poor
      long-term prognosis. RESULTS: Despite variable results, some authors have
      reported a not-insignificant improvement in survival rate in liver-metastasis
      patients with hilar lymph node involvement who undergo combined liver resection
      and lymphadenectomy. Due to the low rates of morbidity and mortality for liver
      resection surgery, several specialized centers perform liver resections combined
      with lymphadenectomies in selected cases. It should be noted that the therapeutic
      value of systemic lymphadenectomy is not yet entirely understood, and only
      controlled studies comparing groups with and without lymphadenectomy can fully
      resolve the issue. CONCLUSION: In any case, hilar lymph node dissection has been
      shown to be a useful tool for improving the accuracy of extra hepatic disease
      staging, regardless of its impact on survival.

PMID- 21952710
TI  - Capsule endoscopy in clinical practice: four years of experience from a single
      center.
AB  - Capsule endoscopy is a diagnostic method of increasing use nowadays, with various
      applications such as, evaluation of obscure gastrointestinal bleeding, chronic
      diarrhea and anemia. The experience of 4 years is reported in a retrospective
      review of 109 medical records to determine the main indications and the most
      common diagnostic findings and the percentage of positive studies. The main
      indications were obscure bleeding in 65%, chronic anemia in 8%. Vascular lesions
      in 33%, being that, hematocistic spot was found in 53% of studies. The location
      of active bleeding was possible in five patients (4.5%). Capsule endoscopy shows
      a high diagnostic yield in obscure bleeding.

PMID- 21952711
TI  - N-1-(2-mercaptoethyl)thymine modification of gold nanoparticles: a highly
      selective and sensitive colorimetric chemosensor for Hg2+.
AB  - An approach for mercury ions (Hg(2+)) sensing based on the Hg(2+)-induced
      aggregation of thymine (T)-SH-functionalized gold nanoparticles (AuNPs) has been
      reported. The T-SH ligands that we synthesized can easily be coupled to the
      surface of AuNPs through the Au-S bond and can recognize Hg(2+) with high
      selectivity by forming a T-Hg-T complex with strong affinity. For the T-SH
      functionalized AuNPs (T-S-AuNPs) sensor, upon addition of Hg(2+), the formation
      of the T-Hg-T complex induces aggregation of T-S-AuNPs and results in a
      significant change of color and UV-Vis absorption spectra. Thus, our method can
      be used for the rapid, easy and reliable screening of Hg(2+) in aqueous solution,
      with high sensitivity (2.8 nM) and selectivity over competing analytes. The
      developed method is successfully applied to the sensing of Hg(2+) in real
      environmental samples.

PMID- 21952712
TI  - Revisiting the holo- and hemidirected structural transition within the
      [Pb(CO)n]2+ model series using first-principles molecular dynamics.
AB  - In this article, we resort to first-principles molecular dynamic simulations to
      examine the thermal effects on the structure of [Pb(CO)(n)](2+) complexes. Values
      of n are chosen to sample structures where hemidirected (n = 2, 4 and 6) or
      holodirected (n = 7 and 8) structures are found when using static approaches. In
      all cases, highly flexible structures are observed. In particular,
      hemidirectional distortions are characterized using geometrical and topological
      analysis. The octacarbonyl complex exhibits the decoordination of one of its
      carbonyl ligands at 300 K.

PMID- 21952713
TI  - Direct arylation of unactivated aromatic C-H bonds catalyzed by a stable organic
      radical.
AB  - A stable zwitterionic radical can catalyze direct arylation of unactivated
      aromatic C-H bonds via a chain homolytic aromatic substitution mechanism in the
      presence of potassium tert-butoxide.

PMID- 21952714
TI  - Accelerated versus nonaccelerated rehabilitation after anterior cruciate ligament
      reconstruction: a prospective, randomized, double-blind investigation evaluating
      knee joint laxity using roentgen stereophotogrammetric analysis.
AB  - BACKGROUND: The relationship between the biomechanical dose of rehabilitation
      exercises administered after anterior cruciate ligament (ACL) reconstruction and
      the healing response of the graft and knee is not well understood. HYPOTHESIS:
      After ACL reconstruction, rehabilitation administered with either accelerated or
      nonaccelerated programs produces the same change in the knees' 6 degrees of
      freedom, or envelope, laxity values. STUDY DESIGN: Randomized controlled trial;
      Level of evidence, 1. METHODS: Patients who underwent ACL reconstruction with a
      bone-patellar tendon-bone autograft were randomized to rehabilitation with either
      accelerated (19 week) or nonaccelerated (32 week) programs. At the time of
      surgery, and then 3, 6, 12, and 24 months later, the 6 degrees of freedom knee
      laxity values were measured using roentgen stereophotogrammetric analysis and
      clinical, functional, and patient-oriented outcome measures. RESULTS: Eighty-five
      percent of those enrolled were followed through 2 years. Laxity of the
      reconstructed knee was restored to within the limits of the contralateral, normal
      side at the time of surgery (baseline) in all participants. Patients in both
      programs underwent a similar increase in the envelope of knee laxity over the 2
      year follow-up interval (anterior-posterior translation 3.2 vs 4.5 mm, and
      coupled internal-external rotations 2.6 degrees  vs 1.9 degrees  for participants
      in the accelerated and nonaccelerated programs, respectively). Those who
      underwent accelerated rehabilitation experienced a significant improvement in
      thigh muscle strength at the 3-month follow-up (P < .05) compared with those who
      participated in nonaccelerated rehabilitation, but no differences between the
      programs were seen after this time interval. At the 2-year follow-up, the groups
      were similar in terms of clinical assessment, patient satisfaction, function,
      proprioception, and isokinetic thigh muscle strength. CONCLUSION: Rehabilitation
      with the accelerated and nonaccelerated programs administered in this study
      produced the same increase in the envelope of knee laxity. A majority of the
      increase in the envelope of knee laxity occurred during healing when exercises
      were advanced and activity level increased. Patients in both programs had the
      same clinical assessment, functional performance, proprioception, and thigh
      muscle strength, which returned to normal levels after healing was complete. For
      participants in both treatment programs, the Knee Injury and Osteoarthritis
      Outcome Score (KOOS) assessment of quality of life did not return to preinjury
      levels.

PMID- 21952715
TI  - Cartilage injury after acute, isolated anterior cruciate ligament tear: immediate
      and longitudinal effect with clinical/MRI follow-up.
AB  - BACKGROUND: Anterior cruciate ligament (ACL) tears have been implicated in the
      development of osteoarthritis. Limited data exist on longitudinal follow-up of
      isolated ACL injury. HYPOTHESES: All isolated ACL tears are associated with some
      degree of cartilage injury that will deteriorate over time. There is a threshold
      of magnetic resonance imaging (MRI)-detectable cartilage injury that will
      correlate with adverse change in subjective patient-reported outcome measures.
      STUDY DESIGN: Cohort study, Level of evidence, 2. METHODS: The authors conducted
      a prospective, observational analysis of 42 knees in 40 patients with acute,
      isolated ACL injury (14 treated nonoperatively, 28 by reconstruction) with
      imaging at the time of injury and yearly follow-up for a maximum of 11 years.
      Morphologic MRI and quantitative T2 mapping was performed with validated outcome
      measures. RESULTS: All patients sustained chondral damage at initial injury. The
      adjusted risk of cartilage loss doubled from year 1 for the lateral compartment
      and medial femoral condyle (MFC) and tripled for the patella. By years 7 to 11,
      the risk for the lateral femoral condyle was 50 times baseline, 30 times for the
      patella, and 19 times for the MFC. There was increased risk of cartilage
      degeneration over the medial tibial plateau (MTP) (P = .047; odds ratio = 6.23;
      95% confidence interval [CI], 1.03-37.90) and patella (P = .032; odds ratio =
      4.88; 95% CI, 1.14-20.80) in nonsurgical patients compared with surgically
      treated patients. Size of the bone-marrow edema pattern was associated with
      cartilage degeneration from baseline to year 3 (P = .001 to .039). Each increase
      in the MFC Outerbridge score resulted in a 13-point decrease in the International
      Knee Documentation Committee subjective knee score (P = .0002). Each increase in
      the MTP resulted in a 2.4-point decrease in the activity rating scale (P = .002).
      CONCLUSION: All patients with acute, traumatic ACL disruption sustained a
      chondral injury at the time of initial impact with subsequent longitudinal
      chondral degradation in compartments unaffected by the initial "bone bruise," a
      process that is accelerated at 5 to 7 years' follow-up.

PMID- 21952716
TI  - Circumferential labral tears resulting from a single anterior glenohumeral
      instability event: a report of 3 cases in young athletes.

PMID- 21952717
TI  - Organocatalytic enantioselective formal synthesis of bromopyrrole alkaloids via
      aza-Michael addition.
AB  - An unprecedented organocatalytic enantioselective formal synthesis of
      bromopyrrole alkaloid natural products is reported. An organocatalytic aza
      Michael addition using pyrroles as the N-centered nucleophile is utilized as the
      enantioselective step to construct the nitrogen-substituted stereogenic carbon
      center in bromopyrrole alkaloids in good yield and excellent enantioselectivity.
      The aza-Michael product is converted via lactamization using a Staudinger-type
      reductive cyclization to the key intermediate, which was previously used in the
      total synthesis of bromopyrrole alkaloid natural products.

PMID- 21952718
TI  - Structural and magnetic properties of Zn-substituted cobalt ferrites prepared by
      co-precipitation method.
AB  - Zn substituted cobalt ferrite spinels with the general formula Zn(x)Co(1
      x)Fe(2)O(4) (with x varying from 0 to 0.5) were synthesized by a co-precipitation
      method and calcined at 500  degrees C and 800  degrees C. It was found that Zn
      substitution has a big effect in decreasing the Curie temperature (T(c)), from
      around 440  degrees C for the undoped sample to ~180  degrees C with x = 0.5.
      However, these values were also strongly affected by the pre-calcination
      temperature of the samples, thus T(C) shifts from ~275  degrees C for the x = 0.3
      sample to ~296  degrees C after calcination at 500  degrees C and 800  degrees C
      respectively. These effects are due to facilitation of demagnetisation by
      substitution of the non-magnetic Zn ions and by production of very small
      nanoparticles. The latter are removed by higher temperature calcinations and so
      T(C) increases.

PMID- 21952719
TI  - Association of TMEM18 variants with BMI and waist circumference in children and
      correlation of mRNA expression in the PFC with body weight in rats.
AB  - Genome-wide association studies have shown a strong association of single
      nucleotide polymorphisms (SNPs) in the near vicinity of the TMEM18 gene. The
      effects of the TMEM18-associated variants are more readily observed in children.
      TMEM18 encodes a 3TM protein, which locates to the nuclear membrane. The
      functional context of TMEM18 and the effects of its associated variants are as of
      yet undetermined. To further explore the effects of near-TMEM18 variants, we have
      genotyped two TMEM18-associated SNPs, rs6548238 and rs4854344, in a cohort of
      2352 Greek children (Healthy Growth Study). Included in this study are data on
      anthropomorphic traits body weight, BMI z-score and waist circumference. Also
      included are dietary energy and macronutrient intake as measured via 24-h recall
      interviews. Major alleles of rs6548238 and rs4854344 were significantly
      associated with an increased risk of obesity (odds ratio = 1.489 (1.161-1.910)
      and 1.494 (1.165-1.917), respectively), and positively correlated to body weight
      (P = 0.017, P = 0.010) and waist circumference (P = 0.003, P = 0.003). An
      association to energy and macronutrient intake was not observed in this cohort.
      We also correlated food intake and body weight in a food choice model in rats to
      Tmem18 expression in central regions involved in feeding behavior. We observed a
      strong positive correlation between TMEM18 expression and body weight in the
      prefrontal cortex (PFC) (r = 0.5694, P = 0.0003) indicating a potential role for
      TMEM18 in higher functions related to feeding involving the PFC.

PMID- 21952720
TI  - De novo deletions and duplications detected by array CGH: a study of parental
      origin in relation to mechanisms of formation and size of imbalance.
AB  - We report a large series of 173 patients with physical and/or neurological
      abnormalities and a de novo imbalance identified by array CGH. Breakpoint
      intervals were screened for the presence of low copy repeats (LCRs) to
      distinguish between rearrangements formed by non-allelic homologous recombination
      (NAHR) and rearrangements formed by other mechanisms. We identified significant
      differences in size and parental origin between the LCR-mediated and non-LCR
      groups. Non-LCR imbalances were evenly distributed among the four size intervals
      we defined, whereas LCR-mediated rearrangements had a narrow size distribution,
      predominantly between 1 and 5 Mb (P = 0.001). Among the LCR-mediated
      rearrangements there were equal numbers of maternally and paternally derived
      cases. In contrast, for the non-LCR rearrangements there was a significant excess
      of paternal cases (P = 0.024) over a wide size range including below 1 Mb. Our
      results provide novel evidence that unbalanced chromosome rearrangements are not
      only more frequent in males, but may also arise through different mechanisms than
      those seen in females. Although the paternal imbalances identified in our study
      are evenly distributed throughout the four size groups, there are very few
      maternal imbalances either <1 Mb or >10 Mb. Furthermore, a lower proportion of
      paternal imbalances are LCR mediated (13/71) compared with the maternal
      imbalances (12/30). We hypothesise that imbalances of maternal origin arise
      predominantly through NAHR during meiosis, while the majority of imbalances of
      paternal origin arise through male-specific mechanisms other than NAHR. Our data
      suggest that mitotic mechanisms could be important for the formation of
      chromosome imbalances; however, we found no association with increased paternal
      age.

PMID- 21952721
TI  - Functional regulation of interleukin-31 production by its genetic polymorphism in
      patients with extrinsic atopic dermatitis.

PMID- 21952722
TI  - Synthesis and electrospray mass spectrometry determination of thiolate-protected
      Au55(SR)31 nanoclusters.
AB  - Since the pioneering work of Schmid et al. on phosphine-capped Au(55) clusters,
      the search for thiolated Au(55) has long been of major interest. This work
      reports the synthesis and electrospray ionization mass spectrometry (ESI-MS)
      evidence of Au(55)(SCH(2)CH(2)Ph)(31) clusters.

PMID- 21952723
TI  - The cultivation of a prosocial value orientation through community service: an
      examination of organizational context, social facilitation, and duration.
AB  - Community service is widely regarded as a fundamental experience in preparation
      for good citizenship, but it remains unclear whether common variants of service
      are consequential for civic outcomes. This study examines changes in the relative
      importance assigned to prosocial and egoistic values associated with service
      through different types of organizations, service prompted by external
      contingencies, and service that spans a narrow or wide frame of time. Data were
      drawn from the survey responses of 16,749 secondary school students (50 percent
      female, 28 percent ethnic minority, modal age = 15) who participated in the
      National Educational Longitudinal Study during their sophomore year in 1990 and
      completed a follow-up survey during their senior year in 1992. Results from a
      propensity score analysis indicated that service through humanitarian
      organizations but not other types of organizations was positively associated with
      the adoption of a prosocial value orientation. Service prompted by an
      institutional mandate or social pressure was negatively associated with
      prosociality relative to service characterized as strictly voluntary, although
      all students except those with an initially egoistic value orientation benefited
      from mandatory service relative to no service. While short-term service during
      the sophomore year had no enduring effect, long-term service predicted gains in
      prosociality above and beyond the effect of concurrent service. The findings
      suggest that the relationship between community service and prosocial value
      development can be optimized to the extent that service through a humanitarian
      organization is prompted by autonomy-supportive conditions over the course of 2
      years.

PMID- 21952724
TI  - Combinatorial biosynthesis in plants: a (p)review on its potential and future
      exploitation.
AB  - Combinatorial biochemistry, also called combinatorial biosynthesis, comprises a
      series of methods that establish novel enzyme-substrate combinations in vivo and,
      in turn, lead to the biosynthesis of new, natural product-derived compounds that
      can be used in drug discovery programs. Plants are an extremely rich source of
      bioactive natural products and continue to possess a huge potential for drug
      discovery. In this review, we discuss the state-of-the-art in combinatorial
      biosynthesis methods to generate novel molecules from plants. We debate on the
      progress and potential in biotransformation, mutasynthesis, combinatorial
      metabolism in hybrids, activation of silent plant metabolism and synthetic
      biology in plants to create opportunities for the combinatorial biosynthesis of
      plant-derived natural products, and, ultimately, for drug discovery. The
      therapeutic value of two classes of natural products, the terpenoid indole
      alkaloids and the triterpene saponins, is particularly highlighted.

PMID- 21952725
TI  - Questioning 'participation': a critical appraisal of its conceptualization in a
      Flemish participatory technology assessment.
AB  - This article draws attention to struggles inherent in discourse about the meaning
      of participation in a Flemish participatory technology assessment (pTA) on
      nanotechnologies. It explores how, at the project's outset, key actors (e.g.,
      nanotechnologists and pTA researchers) frame elements of the process like 'the
      public' and draw on interpretive repertoires to fit their perspective. The
      examples call into question normative commitments to cooperation, consensus
      building, and common action that conventionally guide pTA approaches. It is
      argued that pTA itself must reflect an awareness of competing interests and
      perspectives inherent in the discourse associated with the meaning of
      'participation' if it is to incite action beyond vested interests and ensure
      genuine mutual learning.

PMID- 21952726
TI  - Tuning of the morphology of a riboflavin-melamine equimolar supramolecular
      assembly by in situ silver nanoparticle formation.
AB  - Tuning the supramolecular morphology of an equimolar complex of riboflavin and
      melamine by the in situ formation of different size silver nanoparticles,
      affecting the photoluminescence property.

PMID- 21952728
TI  - Hydrodynamic focusing--a versatile tool.
AB  - The control of hydrodynamic focusing in a microchannel has inspired new
      approaches for microfluidic mixing, separations, sensors, cell analysis, and
      microfabrication. Achieving a flat interface between the focusing and focused
      fluids is dependent on Reynolds number and device geometry, and many hydrodynamic
      focusing systems can benefit from this understanding. For applications where a
      specific cross-sectional shape is desired for the focused flow, advection
      generated by grooved structures in the channel walls can be used to define the
      shape of the focused flow. Relative flow rates of the focused flow and focusing
      streams can be manipulated to control the cross-sectional area of the focused
      flows. This paper discusses the principles for defining the shape of the
      interface between the focused and focusing fluids and provides examples from our
      lab that use hydrodynamic focusing for impedance-based sensors, flow cytometry,
      and microfabrication to illustrate the breadth of opportunities for introducing
      new capabilities into microfluidic systems. We evaluate each example for the
      advantages and limitations integral to utilization of hydrodynamic focusing for
      that particular application.

PMID- 21952729
TI  - The Agrobacterium-mediated transformation of common wheat (Triticum aestivum L.)
      and triticale (x Triticosecale Wittmack): role of the binary vector system and
      selection cassettes.
AB  - The influence of two binary vector systems, pGreen and pCAMBIA, on the
      Agrobacterium-mediated transformation ability of wheat and triticale was studied.
      Both vectors carried selection cassettes with bar or nptII driven by different
      promoters. Two cultivars of wheat, Kontesa and Torka, and one cultivar of
      triticale, Wanad, were tested. The transformation rates for the wheat cultivars
      ranged from 0.00 to 3.58% and from 0.00 to 6.79% for triticale. The best values
      for wheat were 3.58% for Kontesa and 3.14% for Torka, and these were obtained
      after transformation with the pGreen vector carrying the nptII selection gene
      under the control of 35S promoter. In the case of the bar selection system, the
      best transformation rates were, respectively, 1.46 and 1.79%. Such rates were
      obtained when the 35S::bar cassette was carried by the pCAMBIA vector; they were
      significantly lower with the pGreen vector. The triticale cultivar Wanad had its
      highest transformation rate after transformation with nptII driven by 35S in
      pCAMBIA. The bar selection system for the same triticale cultivar was better when
      the gene was driven by nos and the selection cassette was carried by pGreen. The
      integration of the transgenes was confirmed with at least three pairs of specific
      starters amplifying the fragments of nptII, bar, or gus. The expression of
      selection genes, measured by reverse transcriptase polymerase chain reaction (RT
      PCR) in relation to the actin gene, was low, ranging from 0.00 to 0.63 for nptII
      and from 0.00 to 0.33 for bar. The highest relative transcript accumulation was
      observed for nptII driven by 35S and expressed in Kontesa that had been
      transformed with pGreen.

PMID- 21952730
TI  - Gene expression analysis identifies new candidate genes associated with the
      development of black skin spots in Corriedale sheep.
AB  - The white coat colour of sheep is an important economic trait. For unknown
      reasons, some animals are born with, and others develop with time, black skin
      spots that can also produce pigmented fibres. The presence of pigmented fibres in
      the white wool significantly decreases the fibre quality. The aim of this work
      was to study gene expression in black spots (with and without pigmented fibres)
      and white skin by microarray techniques, in order to identify the possible genes
      involved in the development of this trait. Five unrelated Corriedale sheep were
      used and, for each animal, the three possible comparisons (three different
      hybridisations) between the three samples of interest were performed.
      Differential gene expression patterns were analysed using different t-test
      approaches. Most of the major genes with well-known roles in skin pigmentation,
      e.g. ASIP, MC1R and C-KIT, showed no significant difference in the gene
      expression between white skin and black spots. On the other hand, many of the
      differentially expressed genes (raw P-value < 0.005) detected in this study, e.g.
      C-FOS, KLF4 and UFC1, fulfil biological functions that are plausible to be
      involved in the formation of black spots. The gene expression of C-FOS and KLF4,
      transcription factors involved in the cellular response to external factors such
      as ultraviolet light, was validated by quantitative polymerase chain reaction
      (PCR). This exploratory study provides a list of candidate genes that could be
      associated with the development of black skin spots that should be studied in
      more detail. Characterisation of these genes will enable us to discern the
      molecular mechanisms involved in the development of this feature and, hence,
      increase our understanding of melanocyte biology and skin pigmentation. In sheep,
      understanding this phenomenon is a first step towards developing molecular tools
      to assist in the selection against the presence of pigmented fibres in white
      wool.

PMID- 21952731
TI  - Binding activity, structure, and immunogenicity of synthetic peptides derived
      from Plasmodium falciparum CelTOS and TRSP proteins.
AB  - Several sporozoite proteins have been associated with Plasmodium falciparum cell
      traversal and hepatocyte invasion, including the cell-traversal protein for
      ookinetes and sporozoites (CelTOS), and thrombospondin-related sporozoite protein
      (TRSP). CelTOS and TRSP amino acid sequences have been finely mapped to identify
      regions specifically binding to HeLa and HepG2 cells, respectively. Three high
      activity binding peptides (HABPs) were found in CelTOS and one HABP was found in
      TRSP, all of them having high alpha-helical structure content. These HABPs'
      specific binding was sensitive to HeLa and HepG2 cells' pre-treatment with
      heparinase I and chondroitinase ABC. Despite their similarity at three
      dimensional (3D) structural level, TRSP and TRAP HABPs located in the TSR domain
      did not compete for the same binding sites. CelTOS and TRSP HABPs were used as a
      template for designing modified sequences to then be assessed in the Aotus monkey
      experimental model. Antibodies directed against these modified HABPs were able to
      recognize both the native parasite protein by immunofluorescence assay and the
      recombinant protein (expressed in Escherichia coli) by Western blot and ELISA
      assays. The results suggested that these modified HABPs could be promising
      targets in designing a fully effective, antimalarial vaccine.

PMID- 21952732
TI  - Ornithinibacillus scapharcae sp. nov., isolated from a dead ark clam.
AB  - A novel Gram-positive, aerobic, motile, hemolytic, endospore-forming and rod
      shaped bacterium TW25(T) was isolated from a dead ark clam during a mass
      mortality event on the South coast of Korea. The strain grew optimally at 30
      degrees C, at pH 8-9, and with 1% (w/v) NaCl. The 16S rRNA gene sequence analysis
      indicated that strain TW25(T) was associated with the genus Ornithinibacillus and
      that it was most closely related to the type strain of Ornithinibacillus
      californiensis (98.5% similarity). The dominant cellular fatty acids were iso
      C15:0, anteiso-C15:0 and C16:0. The peptidoglycan amino acid type was A4beta,
      containing L: -ornithine and D: -aspartic acid. The polar lipids were
      diphosphatidylglycerol, phosphatidylglycerol, four unidentified phospholipids,
      two unidentified aminolipids and two unidentified lipids. The major respiratory
      quinone was menaquinone-7 (MK-7). The G + C content of genomic DNA was 36.7 mol%.
      DNA-DNA hybridization experiments with related strains revealed lower than 11 +/-
      3% relatedness. Based on this polyphasic taxonomic study, strain TW25(T)
      represents a novel species in the genus Ornithinibacillus, for which the name
      Ornithinibacillus scapharcae sp. nov. is proposed. The type strain is TW25(T)
      (=KACC 15116(T) = JCM 17314(T)).

PMID- 21952733
TI  - Secretome of apoptotic peripheral blood cells (APOSEC) confers cytoprotection to
      cardiomyocytes and inhibits tissue remodelling after acute myocardial infarction:
      a preclinical study.
AB  - Heart failure following acute myocardial infarction (AMI) is a major cause of
      morbidity and mortality. Our previous observation that injection of apoptotic
      peripheral blood mononuclear cell (PBMC) suspensions was able to restore long
      term cardiac function in a rat AMI model prompted us to study the effect of
      soluble factors derived from apoptotic PBMC on ventricular remodelling after AMI.
      Cell culture supernatants derived from irradiated apoptotic peripheral blood
      mononuclear cells (APOSEC) were collected and injected as a single dose
      intravenously after myocardial infarction in an experimental AMI rat model and in
      a porcine closed chest reperfused AMI model. Magnetic resonance imaging (MRI) and
      echocardiography were used to quantitate cardiac function. Analysis of soluble
      factors present in APOSEC was performed by enzyme-linked immunosorbent assay
      (ELISA) and activation of signalling cascades in human cardiomyocytes by APOSEC
      in vitro was studied by immunoblot analysis. Intravenous administration of a
      single dose of APOSEC resulted in a reduction of scar tissue formation in both
      AMI models. In the porcine reperfused AMI model, APOSEC led to higher values of
      ejection fraction (57.0 vs. 40.5%, p < 0.01), a better cardiac output (4.0 vs.
      2.4 l/min, p < 0.001) and a reduced extent of infarction size (12.6 vs. 6.9%, p <
      0.02) as determined by MRI. Exposure of primary human cardiac myocytes with
      APOSEC in vitro triggered the activation of pro-survival signalling-cascades
      (AKT, Erk1/2, CREB, c-Jun), increased anti-apoptotic gene products (Bcl-2, BAG1)
      and protected them from starvation-induced cell death. Intravenous infusion of
      culture supernatant of apoptotic PBMC attenuates myocardial remodelling in
      experimental AMI models. This effect is probably due to the activation of pro
      survival signalling cascades in the affected cardiomyocytes.

PMID- 21952734
TI  - Small molecule inhibitors that discriminate between protein arginine N
      methyltransferases PRMT1 and CARM1.
AB  - Protein arginine N-methyltransferases (PRMTs) selectively replace N-H for N-CH(3)
      at substrate protein guanidines, a post-translational modification important for
      a range of biological processes, such as epigenetic regulation, signal
      transduction and cancer progression. Selective chemical probes are required to
      establish the dynamic function of individual PRMTs. Herein, model inhibitors
      designed to occupy PRMT binding sites for an arginine substrate and S
      adenosylmethionine (AdoMet) co-factor are described. Expedient access to such
      compounds by modular synthesis is detailed. Remarkably, biological evaluation
      revealed some compounds to be potent inhibitors of PRMT1, but inactive against
      CARM1. Docking studies show how prototype compounds may occupy the binding sites
      for a co-factor and arginine substrate. Overlay of PRMT1 and CARM1 binding sites
      suggest a difference in a single amino acid that may be responsible for the
      observed selectivity.

PMID- 21952735
TI  - Reconstructing the diets of Greek Byzantine populations (6th-15th centuries AD)
      using carbon and nitrogen stable isotope ratios.
AB  - Documentary evidence and artistic representations have traditionally served as
      the primary sources of information about Byzantine diet. According to these
      sources, Byzantine diet was based on grain (primarily wheat and barley), oil, and
      wine, supplemented with legumes, dairy products, meat, and marine resources.
      Here, we synthesize and compare the results of stable isotope ratio analyses of
      eight Greek Byzantine populations (6th-15th centuries AD) from throughout Greece.
      The delta(13) C and delta(15) N values are tightly clustered, suggesting that all
      of these populations likely consumed a broadly similar diet. Both inland and
      coastal Byzantine populations consumed an essentially land-based C(3) diet,
      significant amounts of animal protein, and possibly some C(4) plants, while no
      evidence of a general dependence on low-delta(15) N legumes was observed. One
      interesting result observed in the isotopic data is the evidence for the
      consumption of marine protein at both coastal sites (a reasonable expectation
      given their location) and for some individuals from inland sites. This pattern
      contrasts with previous isotopic studies mainly on prehistoric Greek populations,
      which have suggested that marine species contributed little, or not at all, to
      the diet. The possibility that fasting practices contributed to marine protein
      consumption in the period is discussed, as are possible parallels with published
      isotope data from western European medieval sites.

PMID- 21952736
TI  - Molecular imaging of cartilage damage of finger joints in early rheumatoid
      arthritis with delayed gadolinium-enhanced magnetic resonance imaging.
AB  - OBJECTIVE: To assess cartilage glycosaminoglycan content and cartilage thickness
      in the metacarpophalangeal (MCP) joints of patients with early rheumatoid
      arthritis (RA) and healthy volunteers. METHODS: After review board approval and
      informed consent were obtained, 22 subjects were prospectively enrolled (9
      patients with early RA [7 women and 2 men with a mean +/- SD age of 49 +/- 13
      years; range 25-68 years] and 13 healthy volunteers [10 women and 3 men with a
      mean +/- SD age of 51 +/- 12 years; range 25-66 years). In a total of 44 MCP
      joints of the index and middle fingers, measurements of cartilage thickness and
      delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage
      (dGEMRIC) index (T1 [msec]) were obtained using the variable flip-angle method
      and a 3T MR scanner. MRIs were evaluated for bone edema, erosions, and synovitis
      (using the RA MRI Scoring criteria). Student's t-test was used to test the
      significance of differences between groups. RESULTS: The mean +/- SD dGEMRIC
      index was 497 +/- 86 msec in healthy volunteers and was significantly lower in
      the early RA group (421 +/- 76 msec) (P = 0.042). There was no joint space
      narrowing seen on standard radiographs. No significant difference was found
      between cartilage thickness in patients with early RA and that in controls (index
      finger mean +/- SD 1.27 +/- 0.23 mm in RA patients versus 1.46 +/- 0.34 mm in
      controls [P = 0.16] and middle finger 1.26 +/- 0.23 mm in RA patients versus 0.97
      +/- 0.47 mm in controls [P = 0.10]). No significant correlation was noted between
      cartilage thickness and dGEMRIC index (R = 0.36, P = 0.88 in RA patients; R =
      0.156, P = 0.445 in controls). CONCLUSION: Our findings indicate that cartilage
      damage is present in the MCP joints of patients with early RA despite the absence
      of joint space narrowing on standard radiographs and MRI. Cartilage damage in RA
      can be imaged with dGEMRIC.

PMID- 21952737
TI  - Functional and morphological effects of resistance exercise on disuse-induced
      skeletal muscle atrophy.
AB  - Abstract quality of life. Since there is no currently effective and safe
      treatment available for skeletal muscle atrophy, the search for new alternatives
      is necessary. Resistance exercise (RE) seems to be an important tool in the
      treatment of disuse-induced skeletal muscle atrophy by promoting positive
      functional (strength and power) and structural (hypertrophy and phenotypic
      changes) adaptive responses. Human and animal studies using different types of
      resistance exercise (flywheel, vascular occlusion, dynamic, isometric, and
      eccentric) have obtained results of great importance. However, since RE is a
      complex phenomenon, lack of strict control of its variables (volume, frequency,
      intensity, muscle action, rest intervals) limits the interpretation of the impact
      of the manipulation on skeletal muscle remodeling and function under disuse. The
      aim of this review is to critically describe the functional and morphological
      role of resistance exercise in disuse-induced skeletal muscle atrophy with
      emphasis on the principles of training.

PMID- 21952738
TI  - TRP channels, omega-3 fatty acids, and oxidative stress in neurodegeneration:
      from the cell membrane to intracellular cross-links.
AB  - The transient receptor potential channels family (TRP channels) is a relatively
      new group of cation channels that modulate a large range of physiological
      mechanisms. In the nervous system, the functions of TRP channels have been
      associated with thermosensation, pain transduction, neurotransmitter release, and
      redox signaling, among others. However, they have also been extensively
      correlated with the pathogenesis of several innate and acquired diseases. On the
      other hand, the omega-3 polyunsaturated fatty acids (n-3 fatty acids) have also
      been associated with several processes that seem to counterbalance or to
      contribute to the function of several TRPs. In this short review, we discuss some
      of the remarkable new findings in this field. We also review the possible roles
      played by n-3 fatty acids in cell signaling that can both control or be
      controlled by TRP channels in neurodegenerative processes, as well as both the
      direct and indirect actions of n-3 fatty acids on TRP channels.

PMID- 21952739
TI  - Adeno-associated virus for cystic fibrosis gene therapy.
AB  - Gene therapy is an alternative treatment for genetic lung disease, especially
      monogenic disorders such as cystic fibrosis. Cystic fibrosis is a severe
      autosomal recessive disease affecting one in 2500 live births in the white
      population, caused by mutation of the cystic fibrosis transmembrane conductance
      regulator (CFTR). The disease is classically characterized by pancreatic enzyme
      insufficiency, an increased concentration of chloride in sweat, and varying
      severity of chronic obstructive lung disease. Currently, the greatest challenge
      for gene therapy is finding an ideal vector to deliver the transgene (CFTR) to
      the affected organ (lung). Adeno-associated virus is the most promising viral
      vector system for the treatment of respiratory disease because it has natural
      tropism for airway epithelial cells and does not cause any human disease. This
      review focuses on the basic properties of adeno-associated virus and its use as a
      vector for cystic fibrosis gene therapy.

PMID- 21952741
TI  - Dicarboxylate-bridged (Mo2)n (n = 2, 3, 4) paddle-wheel complexes: potential
      intermediate building blocks for metal-organic frameworks.
AB  - The treatment of the dimeric paddle-wheel (PW) compound
      [Mo(2)(NCCH(3))(10)][BF(4)](4)1 with oxalic acid (0.5 equiv.), 1,1
      cyclobutanedicarboxylic acid (1 equiv.), 5-hydroxyisophthalic acid (1 equiv.) (m
      bdc-OH) or 2,3,5,6-tetrafluoroterephthalic acid (0.5 or 1 equiv.) leads to the
      formation of macromolecular dicarboxylate-linked (Mo(2))(n) entities (n = 2, 3,
      4). The structure of the compounds depends on the length and geometry of the
      organic linkers. In the case of oxalic acid, the dimeric compound
      [(CH(3)CN)(8)Mo(2)(OOC-COO)Mo(2)(NCCH(3))(8)][BF(4)](6)2 is formed selectively,
      whereas the use of 2,3,5,6-tetrafluoroterephthalic acid affords the square-shaped
      complex [(CH(3)CN)(6)Mo(2)(OOC-C(6)F(4)-COO)](4)[BF(4)](8)3. Bent linkers with a
      bridging angle of 109 degrees  and 120 degrees , respectively, lead to the
      formation of the molecular loop [(CH(3)CN)(6)Mo(2)(OOC-C(4)H(6)
      COO)](2)[BF(4)](4)4 and the bowl-shaped molecular triangle [(CH(3)CN)(6)Mo(2)(m
      bdc-OH)](3)[BF(4)](6)5. All complexes are characterised by X-ray single crystal
      diffraction, NMR ((1)H, (11)B, (13)C and (19)F) and UV-Vis spectroscopy.

PMID- 21952740
TI  - Replication of association of the PTPRC gene with response to anti-tumor necrosis
      factor therapy in a large UK cohort.
AB  - OBJECTIVE: Several rheumatoid arthritis (RA) susceptibility variants map close to
      genes involved in the tumor necrosis factor (TNF) signaling pathway, prompting
      the investigation of RA susceptibility variants in studies of predictors of
      response to TNF blockade. Based on a previously reported association of RA with
      the PTPRC genetic locus, the present study was undertaken to test established RA
      susceptibility variants, including PTPRC, in the prediction of response to TNF
      blockade in a large cohort of patients from the UK. METHODS: DNA was extracted
      from the blood of 1,115 UK patients with RA who were receiving anti-TNF biologic
      therapy. Samples were analyzed for 29 single-nucleotide polymorphisms (SNPs)
      previously established as RA susceptibility variants. In the primary analysis,
      the effect of each SNP on treatment response was assessed by linear regression,
      using an additive model, in which absolute change in the Disease Activity Score
      in 28 joints at 6 months of followup was the outcome measure. In a secondary
      analysis, logistic regression models were used to compare patients with a good
      treatment response (n = 274) to those with a poor response (n = 195), as defined
      using the European League Against Rheumatism response criteria. Results were
      combined with those from previous studies to confirm the findings by meta
      analysis. RESULTS: The PTPRC rs10919563 SNP was associated with improved
      treatment response in both the primary analysis (regression coefficient 0.19, 95%
      confidence interval [95% CI] 0.09, 0.37; P = 0.04) and secondary analysis (odds
      ratio 0.62, 95% CI 0.40, 0.95; P = 0.03). A meta-analysis combining these data
      with the results from a previous study strengthened the evidence for association
      with the PTPRC SNP (P = 5.13 * 10(-5) ). No convincing association of the
      treatment response with other candidate loci was detected. CONCLUSION: Presence
      of the rs10919563 RA susceptibility variant at the PTPRC gene locus predicts
      improved response to anti-TNF biologic therapy. Fine-mapping studies are required
      to determine whether this SNP or another variant at the locus provides the
      greatest predictive accuracy for treatment response.

PMID- 21952742
TI  - Standardized diagnostic criteria for developmental dysplasia of the hip in early
      infancy.
AB  - BACKGROUND: Clinicians use various criteria to diagnose developmental dysplasia
      of the hip (DDH) in early infancy, but the importance of these various criteria
      for a definite diagnosis is controversial. The lack of uniform, widely agreed-on
      diagnostic criteria for DDH in patients in this age group may result in a delay
      in diagnosis of some patients. QUESTIONS/PURPOSES: Our purpose was to establish a
      consensus among pediatric orthopaedic surgeons worldwide regarding the most
      relevant criteria for diagnosis of DDH in infants younger than 9 weeks. MATERIAL
      AND METHODS: We identified 212 potential criteria relevant for diagnosing DDH in
      infants by surveying 467 professionals. We used the Delphi technique to reach a
      consensus regarding the most important criteria. We then sent the survey to 261
      orthopaedic surgeons from 34 countries. RESULTS: The response rate was 75%.
      Thirty-seven items were identified by surgeons as most relevant to diagnose DDH
      in patients in this age group. Of these, 10 of 37 (27%) related to patient
      characteristics and history, 13 of 37 (35%) to clinical examination, 11 of 37
      (30%) to ultrasound, and three of 37 (8%) to radiography. A Cronbach alpha of 0.9
      for both iterations suggested consensus among the panelists. CONCLUSION: We
      established a consensus regarding the most relevant criteria for the diagnosis of
      DDH in early infancy and established their relative importance on an
      international basis. The highest ranked clinical criteria included the
      Ortolani/Barlow test, asymmetry in abduction of 20 degrees  or greater, breech
      presentation, leg-length discrepancy, and first-degree relative treated for DDH.
      LEVEL OF EVIDENCE: Level IV, diagnostic study. See the Guidelines for Authors for
      a complete description of levels of evidence.

PMID- 21952743
TI  - Cauda equina syndrome after a TLIF resulting from postoperative expansion of a
      hydrogel dural sealant.
AB  - BACKGROUND: DuraSeal(TM) (Coviden, Waltham, MA, USA), a hydrogel sealant, is
      primarily used as an adjunct to a dural repair. Its use has also been described
      to seal off an annulotomy after a transforaminal lumbar interbody fusion when
      recombinant human bone morphogenetic protein-2 (rhBMP-2) is used. This aids in
      the reduction of postoperative radiculitis caused by rhBMP-2. However, as a
      result of its hydrophilic properties, DuraSeal(TM) has the potential to swell,
      which could lead to compression of the thecal sac. CASE DESCRIPTION: We report a
      57-year-old woman who developed cauda equina after a transforaminal lumbar 47
      interbody fusion (TLIF) procedure in which the expansion of the DuraSeal(TM) was
      believed to be the causative factor. The patient developed urinary retention,
      bowel incontinence, and paresthesias in the saddle region on postoperative Day 3.
      She underwent emergent exploration and decompression of the thecal sac. The gel
      like DuraSealTM material was causing significant compression of the thecal sac.
      LITERATURE REVIEW: Multiple reports have documented that DuraSeal(TM), used as an
      adjunct to dural repair, can swell leading to compression of the spinal cord
      and/or neural elements. Our case demonstrates the use of DuraSeal(TM) both over a
      site of a dural repair and over an annulotomy site, through which a TLIF was
      performed, is associated with the risk of developing postoperative cauda equina
      syndrome as a result of swelling of the DuraSeal(TM). CLINICAL RELEVANCE: Those
      using DuraSealTM to seal off the annulotomy after a TLIF procedure performed with
      rhBMP-2 should use the product with an understanding of the potential
      postoperative swelling of the product and resulting neurologic sequela,
      particularly if DuraSeal(TM) is used concomitantly at the site of dural repair.

PMID- 21952744
TI  - Public reporting of cost and quality information in orthopaedics.
AB  - BACKGROUND: Public reporting of patient health outcomes offers the potential to
      incentivize quality improvement by fostering increased accountability among
      providers. Voluntary reporting of risk-adjusted outcomes in cardiac surgery, for
      example, is viewed as a "watershed event" in healthcare accountability. However,
      public reporting of outcomes, cost, and quality information in orthopaedic
      surgery remains limited by comparison, attributable in part to the lack of
      standard assessment methods and metrics, provider fear of inadequate adjustment
      of health outcomes for patient characteristics (risk adjustment), and
      historically weak market demand for this type of information. QUESTIONS/PURPOSES:
      We review the origins of public reporting of outcomes in surgical care, identify
      existing initiatives specific to orthopaedics, outline the challenges and
      opportunities, and propose recommendations for public reporting of orthopaedic
      outcomes. METHODS: We performed a comprehensive review of the literature through
      a bibliographic search of MEDLINE and Google Scholar databases from January 1990
      to December 2010 to identify articles related to public reporting of surgical
      outcomes. RESULTS: Orthopaedic-specific quality reporting efforts include the
      early FDA adverse event reporting MedWatch program and the involvement of
      surgeons in the Physician Quality Reporting Initiative. Issues that require more
      work include balancing different stakeholder perspectives on quality reporting
      measures and methods, defining accountability and attribution for outcomes, and
      appropriately risk-adjusting outcomes. CONCLUSIONS: Given the current limitations
      associated with public reporting of quality and cost in orthopaedic surgery,
      valuable contributions can be made in developing specialty-specific evidence
      based performance measures. We believe through leadership and involvement in
      policy formulation and development, orthopaedic surgeons are best equipped to
      accurately and comprehensively inform the quality reporting process and its
      application to improve the delivery and outcomes of orthopaedic care.

PMID- 21952745
TI  - Perioperative closure-related complication rates and cost analysis of barbed
      suture for closure in TKA.
AB  - BACKGROUND: The use of barbed suture for surgical closure has been associated
      with lower operative times, equivalent wound complication rate, and comparable
      cosmesis scores in the plastic surgery literature. Similar studies would help
      determine whether this technology is associated with low complication rates and
      reduced operating times for orthopaedic closures. QUESTIONS/PURPOSES: We compared
      a running barbed suture with an interrupted standard suture technique for layered
      closure in primary TKA to determine if the barbed suture would be associated with
      (1) shorter estimated closure times; (2) lower cost; and (3) similar closure
      related perioperative complication rates. METHODS: We retrospectively compared
      two-layered closure techniques in primary TKA with either barbed or knotted
      sutures. The barbed group consisted of 104 primary TKAs closed with running
      barbed suture. The standard group consisted of 87 primary TKAs closed with
      interrupted suture. Cost analysis was based on cost of suture and operating room
      time. Clinical records were assessed for closure-related complications within the
      6-week perioperative period. RESULTS: Average estimated closure time was 2.3
      minutes shorter with the use of barbed suture. The total closure cost was similar
      between the groups. The closure-related perioperative complication rates were
      similar between the groups. CONCLUSIONS: Barbed suture is associated with a
      slightly shorter estimated closure time, although this small difference is of
      questionable clinical importance. With similar overall cost and no difference in
      perioperative complications in primary TKA, this closure methodology has led to
      more widespread use at our institution.

PMID- 21952746
TI  - Rosacea treatment with intermediate-dose isotretinoin: follow-up with erythema
      and sebum measurements.
AB  - Isotretinoin is one of the therapeutic options for rosacea. However, the response
      of erythema to treatment with isotretinoin is usually slow and incomplete with
      common (0.5-1 mg/kg/day) or low (10 mg/day) doses. This study investigated the
      efficacy of, and relapse on, 20 mg/day isotretinoin treatment in rosacea, with
      the aid of instrumental measurement of facial erythema and sebum levels. A 20
      mg/day dose of isotretinoin was given for 4 months, and then the dose was tapered
      off within the following 6 months. A total of 25 patients were included in the
      study. Papule and pustule counts, erythema index, sebum level, dermatologist's
      and patient's erythema scores, and dermatologist's sebum scores were
      significantly lower in the first month of therapy compared with pre-treatment
      values (p < 0.05). Within a median follow-up of 11 months (95% confidence
      interval: 8.4-13.5 months) 45% of patients had a relapse. In conclusion, 20
      mg/day isotretinoin was rapidly efficient for reducing both inflammatory lesions
      and erythema in rosacea.

PMID- 21952747
TI  - Doping dependent crystal structures and optoelectronic properties of n-type
      CdSe:Ga nanowries.
AB  - Although CdSe nanostructures possess excellent electrical and optical properties,
      efforts to make nano-optoelectronic devices from CdSe nanostructures have been
      hampered by the lack of efficient methods to rationally control their structural
      and electrical characteristics. Here, we report CdSe nanowires (NWs) with doping
      dependent crystal structures and optoelectronic properties by using gallium (Ga)
      as the efficient n-type dopant via a simple thermal co-evaporation method. The
      phase change of CdSe NWs from wurtzite to zinc blende with increased doping level
      is observed. Systematical measurements on the transport properties of the CdSe:Ga
      NWs reveal that the NW conductivity could be tuned in a wide range of near nine
      orders of magnitude by adjusting the Ga doping level and a high electron
      concentration up to 4.5 * 10(19) cm(-3) is obtained. Moreover, high-performance
      top-gate field-effect transistors are constructed based on the individual CdSe:Ga
      NWs by using high-kappa HfO(2) as the gate dielectric. The great potential of the
      CdSe:Ga NWs as high-sensitive photodetectors and nanoscale light emitters is also
      exploited, revealing the promising applications of the CdSe:Ga NWs in new
      generation nano-optoelectronics.

PMID- 21952748
TI  - EGFR- and AKT-mediated reduction in PTEN expression contributes to tyrphostin
      resistance and is reversed by mTOR inhibition in endometrial cancer cells.
AB  - Loss or mutation of the PTEN (phosphatase and tensin homologue deleted on
      chromosome 10) gene is associated with resistance to epidermal growth factor
      receptor (EGFR) inhibitors. However, the mechanism underlying remains elusive. In
      this study, we aimed to explore whether sensitivity to the EGFR tyrosine kinase
      inhibitor (TKI) is affected by PTEN status in endometrial cancer cells. PTEN
      siRNA and the PTEN gene were transfected into HEC-1A and Ishikawa endometrial
      cancer cells using lentiviral vectors. Cells were treated under various
      concentrations of RG14620 and rapamycin, which are EGFR and mammalian target of
      rapamycin (mTOR) inhibitors, respectively. The IC(50) of RG16420 was determined
      by using the MTT method. Cell apoptosis and the cell cycle were studied, and
      activation of EGFR, AKT, and p70S6 were detected by Western blot analysis. Loss
      of PTEN promoted cell proliferation and led to significant increases in the
      levels of EGFR, phospho-EGFR, AKT, phospho-AKT, and phospho-mTOR proteins.
      Ishikawa and HEC-1A(PTENkd) cells that displayed loss and inactivation of PTEN
      function were resistant to RG14620. HEC-1A and Ishikawa(PTEN) cells with intact
      PTEN were sensitive to RG14620. The combination of two inhibitors was more
      effective than both monotherapies, particularly in carcinoma cells with PTEN
      dysfunction. Decreased phospho-EGFR protein expression was observed in all cell
      lines that were sensitive to RG14620. Decreased phospho-AKT and phospho-p70S6
      protein expression was observed in PTEN-intact cells that were sensitive to
      RG14620. PTEN loss results in resistance to EGFR TKI, which was reversed by PTEN
      reintroduction or mTOR inhibitor treatment. The combined treatment of EGFR TKI
      and the mTOR inhibitor provided a synergistic effect by promoting cell death in
      PTEN-deficient and PTEN-intact endometrial cancer cells, particularly in PTEN
      deficient carcinoma cells with up-regulated EGFR activation.

PMID- 21952749
TI  - Isoniazid metal complex reactivity and insights for a novel anti-tuberculosis
      drug design.
AB  - For over a decade, tuberculosis (TB) has been the leading cause of death among
      infectious diseases. Since the 1950s, isoniazid has been used as a front-line
      drug in the treatment of TB; however, resistant TB strains have limited its use.
      The major route of isoniazid resistance relies on KatG enzyme disruption, which
      does not promote an electron transfer reaction. Here, we investigated the
      reactivity of isoniazid metal complexes as prototypes for novel self-activating
      metallodrugs against TB with the aim to overcome resistance. Reactivity studies
      were conducted with hydrogen peroxide, hexacyanoferrate(III), and
      aquopentacyanoferrate(III). The latter species showed a preference for the inner
      sphere electron transfer reaction pathway. Additionally, electron transfer
      reaction performed with either free isoniazid or (isoniazid)pentacyanoferrate(II)
      complex resulted in similar oxidized isoniazid derivatives as observed when the
      KatG enzyme was used. However, upon metal coordination, a significant enhancement
      in the formation of isonicotinic acid was observed compared with that of
      isonicotinamide. These results suggest that the pathway of a carbonyl-centered
      radical might be favored upon coordination to the Fe(II) owing to the pi-back
      bonding effect promoted by this metal center; therefore, the isoniazid metal
      complex could serve as a potential metallodrug. Enzymatic inhibition assays
      conducted with InhA showed that the cyanoferrate moiety is not the major player
      involved in this inhibition but the presence of isoniazid is required in this
      process. Other isoniazid metal complexes, [Ru(CN)(5)(izd)](3-) and
      [Ru(NH(3))(5)(izd)](2+) (where izd is isoniazid), were also unable to inhibit
      InhA, supporting our proposed self-activating mechanism of action. We propose
      that isoniazid reactivity can be rationally modulated by metal coordination
      chemistry, leading to the development of novel anti-TB metallodrugs.

PMID- 21952751
TI  - Acquired pH-responsive and reversible enrichment of organic dyes by peroxide
      modified ultrathin TiO2 nanosheets.
AB  - The acquired pH-responsive and reversible enrichment of organic dyes from aqueous
      solutions by peroxide modified ultrathin nanosheets of anatase and TiO(2)(B) is
      illustrated in comparison with P25 and TiO(2)(B) nanowires.

PMID- 21952750
TI  - Prognostic impact of insulin receptor expression on survival of patients with
      nonsmall cell lung cancer.
AB  - BACKGROUND: The purpose of this study was to characterize insulin receptor (IR)
      and insulin-like growth factor-1 receptor (IGF-1R) expression in patients with
      nonsmall cell lung cancer (NSCLC). METHODS: A total of 459 patients who underwent
      curative resection of NSCLC were studied (median follow-up duration, 4.01 years).
      Expression of the IR and IGF-1R protein in tumor specimens was assessed
      immunohistochemically using tissue microarrays. RESULTS: The cytoplasmic IR score
      was higher in patients with adenocarcinoma (ADC) than in those with squamous cell
      carcinoma (SCC), whereas cytoplasmic IGF-1R score was higher in patients with SCC
      than those with ADC. Neither IR nor IGF-1R expression was associated with sex,
      smoking history, or clinical stage. Patients with positive IR or IGF-1R
      expression levels had poor recurrence-free (RFS) (3.8 vs 3.3 years; 3.8 vs 2.0
      years, respectively), but similar overall survival (OS). Patients with high
      expression levels of IR and IGF-1R had shorter RFS and OS compared with those
      with low levels of IR and/or IGF-1R expression. Finally, a multivariate analysis
      revealed the impact of IR, but not of IGF-1R, as an independent predictive marker
      of NSCLC survival: hazard ratio (HR) for OS, 1.005 (95% confidence interval [CI],
      1.001-1.010], HR for RFS, 1.005 (95% CI, 1.001-1.009), when IR score was tested
      as a continuous variable. CONCLUSIONS: Overexpression of IR predicts a poor
      survival among patients with NSCLC, especially those with SCC. These results
      might serve as future guidance to the clinical trials involving IR or IGR-1R
      targeting agents.

PMID- 21952752
TI  - Tunable charge tags for electron-based methods of peptide sequencing: design and
      applications.
AB  - Charge tags using basic auxiliary functional groups 6-aminoquinolinylcarboxamido,
      4-aminopyrimidyl-1-methylcarboxamido, 2-aminobenzoimidazolyl-1-methylcarboxamido,
      and the fixed-charge 4-(dimethylamino)pyridyl-1-carboxamido moiety are evaluated
      as to their properties in electron transfer dissociation mass spectra of arginine
      C-terminated peptides. The neutral tags have proton affinities that are
      competitive with those of amino acid residues in peptides. Charge reduction by
      electron transfer from fluoranthene anion-radicals results in peptide backbone
      dissociations that improve sequence coverage by providing extensive series of N
      terminal c-type fragments without impeding the formation of C-terminal z
      fragments. Comparison of ETD mass spectra of free and tagged peptides allows one
      to resolve ambiguities in fragment ion assignment through mass shifts of c ions.
      Simple chemical procedures are reported for N-terminal tagging of Arg-containing
      tryptic peptides.

PMID- 21952754
TI  - An unusual family of glycosylated peptides isolated from Dendroaspis angusticeps
      venom and characterized by combination of collision induced and electron transfer
      dissociation.
AB  - This study describes the structural characterization of a totally new family of
      peptides from the venom of the snake green mamba (Dendroaspis angusticeps).
      Interestingly, these peptides differ in several points from other already known
      mamba toxins. First of all, they exhibit very small molecular masses, ranging
      from 1.3 to 2.4 kDa. The molecular mass of classical mamba toxins is in the range
      of 7 to 25 kDa. Second, the new peptides do not contain disulfide bonds, a post
      translational modification commonly encountered in animal toxins. The third
      difference is the very high proportion of proline residues in the sequence
      accounting for about one-third of the sequence. Finally, these new peptides
      reveal a carbohydrate moiety, indicating a glycosylation in the sequence. The
      last two features have made the structural characterization of the new peptides
      by mass spectrometry a real analytical challenge. Peptides were characterized by
      a combined use of MALDI- TOF/TOF and nanoESI-IT-ETD experiments to determine not
      only the peptide sequence but also the composition and the position of the
      carbohydrate moiety. Anyway, such small glycosylated and proline-rich toxins are
      totally different from any other known snake peptide and form, as a consequence,
      a new family of peptides.

PMID- 21952755
TI  - Numerical simulation and experimental validation of the three-dimensional flow
      field and relative analyte concentration distribution in an atmospheric pressure
      ion source.
AB  - In this study, the validation and analysis of steady state numerical simulations
      of the gas flows within a multi-purpose ion source (MPIS) are presented. The
      experimental results were obtained with particle image velocimetry (PIV)
      measurements in a non-scaled MPIS. Two-dimensional time-averaged velocity and
      turbulent kinetic energy distributions are presented for two dry gas volume flow
      rates. The numerical results of the validation simulations are in very good
      agreement with the experimental data. All significant flow features have been
      correctly predicted within the accuracy of the experiments. For technical
      reasons, the experiments were conducted at room temperature. Thus, numerical
      simulations of ionization conditions at two operating points of the MPIS are also
      presented. It is clearly shown that the dry gas volume flow rate has the most
      significant impact on the overall flow pattern within the APLI source; far less
      critical is the (larger) nebulization gas flow. In addition to the approximate
      solution of Reynolds-Averaged Navier-Stokes equations, a transport equation for
      the relative analyte concentration has been solved. The results yield information
      on the three-dimensional analyte distribution within the source. It becomes
      evident that for ion transport into the MS ion transfer capillary,
      electromagnetic forces are at least as important as fluid dynamic forces.
      However, only the fluid dynamics determines the three-dimensional distribution of
      analyte gas. Thus, local flow phenomena in close proximity to the spray shield
      are strongly impacting on the ionization efficiency.

PMID- 21952753
TI  - Sulfonium ion derivatization, isobaric stable isotope labeling and data dependent
      CID- and ETD-MS/MS for enhanced phosphopeptide quantitation, identification and
      phosphorylation site characterization.
AB  - An amine specific peptide derivatization strategy involving the use of novel
      isobaric stable isotope encoded 'fixed charge' sulfonium ion reagents, coupled
      with an analysis strategy employing capillary HPLC, ESI-MS, and automated data
      dependent ion trap CID-MS/MS, -MS(3), and/or ETD-MS/MS, has been developed for
      the improved quantitative analysis of protein phosphorylation, and for
      identification and characterization of their site(s) of modification.
      Derivatization of 50 synthetic phosphopeptides with S,S'
      dimethylthiobutanoylhydroxysuccinimide ester iodide (DMBNHS), followed by
      analysis using capillary HPLC-ESI-MS, yielded an average 2.5-fold increase in
      ionization efficiencies and a significant increase in the presence and/or
      abundance of higher charge state precursor ions compared to the non-derivatized
      phosphopeptides. Notably, 44% of the phosphopeptides (22 of 50) in their
      underivatized states yielded precursor ions whose maximum charge states
      corresponded to +2, while only 8% (4 of 50) remained at this maximum charge state
      following DMBNHS derivatization. Quantitative analysis was achieved by measuring
      the abundances of the diagnostic product ions corresponding to the neutral losses
      of 'light' (S(CH(3))(2)) and 'heavy' (S(CD(3))(2)) dimethylsulfide exclusively
      formed upon CID-MS/MS of isobaric stable isotope labeled forms of the DMBNHS
      derivatized phosphopeptides. Under these conditions, the phosphate group stayed
      intact. Access for a greater number of peptides to provide enhanced
      phosphopeptide sequence identification and phosphorylation site characterization
      was achieved via automated data-dependent CID-MS(3) or ETD-MS/MS analysis due to
      the formation of the higher charge state precursor ions. Importantly, improved
      sequence coverage was observed using ETD-MS/MS following introduction of the
      sulfonium ion fixed charge, but with no detrimental effects on ETD fragmentation
      efficiency.

PMID- 21952756
TI  - A novel APPI-MS setup for in situ degradation product studies of atmospherically
      relevant compounds: capillary atmospheric pressure photo ionization (cAPPI).
AB  - We report on the development of a novel atmospheric pressure photoionization
      setup and its applicability for in situ degradation product studies of
      atmospherically relevant compounds. A custom miniature spark discharge lamp was
      embedded into an ion transfer capillary, which separates the atmospheric pressure
      from the low pressure region in the first differential pumping stage of a
      conventional atmospheric pressure ionization mass spectrometer. The lamp operates
      with a continuous argon flow and produces intense light emissions in the VUV. The
      custom lamp is operated windowless and efficiently illuminates the sample flow
      through the transfer capillary on an area smaller than 1 mm(2). Limits of
      detection in the lower ppbV range, a temporal resolution of milliseconds in the
      positive as well as the quasi simultaneously operating negative ion mode, and a
      significant reduction of ion transformation processes render this system
      applicable to real time studies of rapidly changing chemical systems. The method
      termed capillary atmospheric pressure photo ionization (cAPPI) is characterized
      with respect to the lamp emission properties as a function of the operating
      conditions, temporal response, and its applicability for in situ degradation
      product studies of atmospherically relevant compounds, respectively.

PMID- 21952758
TI  - Density functional theory and mass spectrometry of phthalate fragmentations
      mechanisms: modeling hyperconjugated carbocation and radical cation complexes
      with neutral molecules.
AB  - This is the first ab initio study of the energetics of the fragmentation
      mechanisms of phthalate, by mass spectrometry, leading to protonated phthalic
      anhydride (m/z 149). Phthalates fragment by two major pathways; namely, the
      McLafferty + 1 rearrangement and the loss of alkoxy. Both pathways involve a
      carbonyl oxygen attack to the ortho-carbonyl carbon leading to structures with
      tetrahedral carbon intermediates that eventually give m/z 149. These pathways
      were studied by collision induced dissociation (CID) using triple quadrupole mass
      spectrometry. The proposed McLafferty + 1 pathway proceeds through a distonic
      M(*+), leading to the loss of an allylic-stabilized alkene radical. The
      McLafferty rearrangement step proceeds through a six-membered ring transition
      state with a small activation energy ranging 0.4-6.2 kcal/mol; the transfer of a
      second H from the distonic ion of the rearrangement step proceeds through a
      radical cation molecule complex. Based on quantum chemical modeling of the cation
      molecule complexes, two kinds of cation molecule complexes were identified as
      radical cation molecule complex and hyperconjugated cation molecule complex. This
      distinction is based on the cation and simplifies future modeling of similar
      complexes. Optimization of important fragments in these pathways showed cyclized
      and hydrogen-bonded structures to be favored. An exception was the optimized
      structure of the protonated phthalic anhydride (m/z 149) that showed a structure
      with an open anhydride ring.

PMID- 21952757
TI  - Simultaneous identification of tyrosine phosphorylation and sulfation sites
      utilizing tyrosine-specific bromination.
AB  - Tyrosine phosphorylation and sulfation play many key roles in the cell. Isobaric
      phosphotyrosine and sulfotyrosine residues in peptides were determined by mass
      spectrometry using phosphatase or sulfatase to remove the phosphate or the
      sulfate group. Unique Br signature was introduced to the resulting tyrosine
      residues by incubation with 32% HBr at -20  degrees C for 20 min. MS/MS analysis
      of the brominated peptide enabled unambiguous determination of the
      phosphotyrosine and the sulfotyrosine sites. When phosphotyrosine and
      sulfotyrosine as well as free tyrosine were present in the same peptide, they
      could be determined simultaneously using either phosphatase or sulfatase
      following acetylation of the free tyrosine.

PMID- 21952759
TI  - Unusual fragmentation of Pro-Ser/Thr-containing peptides detected in collision
      induced dissociation spectra.
AB  - During collision-induced dissociation (CID)-, phosphoserine- and phosphothreonine
      containing peptides frequently undergo neutral loss of phosphoric acid.
      Subsequent amide bond cleavage N-terminal to the site of phosphorylation results
      in a y ion with a mass 18 Da lower than the corresponding unmodified y fragment.
      We report here that when the phosphoserine or phosphothreonine is directly
      preceded by a proline, an unusual fragment with a mass 10 Da higher than the
      corresponding unmodified y ion is frequently observed. Accurate mass measurements
      are consistent with elimination of the phosphoric acid followed by fragmentation
      between the alpha carbon and the carbonyl group of the proline residue. We
      propose a cyclic oxazoline structure for this fragment. Our observation may be
      explained by the charge-directed S(N)2 neighboring group participation reaction
      proposed for the phosphoric acid elimination by Palumbo et al. [Palumbo, A. M.,
      Tepe, J. J., Reid, G. E. Mechanistic Insights into the Multistage Gas-Phase
      Fragmentation Behavior of Phosphoserine- and Phosphothreonine-Containing
      Peptides. J. Protein Res. 7(2), 771-779 (2008)]. Considering such specific
      fragment ions for confirmation purposes after regular database searches may boost
      the confidence of peptide identifications as well as phosphorylation site
      assignments.

PMID- 21952760
TI  - Overtone mobility spectrometry: part 4. OMS-OMS analyses of complex mixtures.
AB  - A new, two-dimensional overtone mobility spectrometry (OMS-OMS) instrument is
      described for the analysis of complex peptide mixtures. OMS separations are based
      on the differences in mobilities of ions in the gas phase. The method utilizes
      multiple drift regions with modulated drift fields such that only ions with
      appropriate mobilities are transmitted to the detector. Here we describe a hybrid
      OMS-OMS combination that utilizes two independently operated OMS regions that are
      separated by an ion activation region. Mobility-selected ions from the first OMS
      region are exposed to energizing collisions and may undergo structural
      transitions before entering the second OMS region. This method generates
      additional peak capacity and allows for higher selectivity compared with the one
      dimensional OMS method. We demonstrate the approach using a three-protein tryptic
      digest spiked with the peptide Substance P. The [M + 3H](3+) ion from Substance P
      can be completely isolated from other components in this complex mixture prior to
      introduction into the mass spectrometer.

PMID- 21952761
TI  - Anion effects on sodium ion and acid molecule adduction to protein ions in
      electrospray ionization mass spectrometry.
AB  - Gaseous protein-metal ion and protein-molecule complexes can be readily formed by
      electrospray ionization (ESI) from aqueous solutions containing proteins and
      millimolar concentrations of sodium salts of various anions. The extent of sodium
      and acid molecule adduction to multiply charged protein ions is inversely related
      and depends strongly on the proton affinity (PA) of the anion, with extensive
      sodium adduction occurring for anions with PA values greater than ~300 kcal.mol(
      1) and extensive acid molecule adduction occurring for anions with PA values less
      than 315 kcal.mol(-1). The role of the anion on the extent of sodium and acid
      molecule adduction does not directly follow the Hofmeister series, suggesting
      that direct protein-ion interactions may not play a significant role in the
      observed effect of anions on protein structure in solution. These results
      indicate that salts with anions that have low PA values may be useful solution
      phase additives to minimize nonspecific metal ion adduction in ESI experiments
      designed to identify specific protein-metal ion interactions.

PMID- 21952762
TI  - Homolytic reactive mass spectrometry of fullerenes: interaction of C60 and C70
      with ketones in the electron impact ion source of a mass spectrometer and the
      comparison of results with those of photochemical reactions of C60 with several
      ketones in solution.
AB  - Our previous investigations showed that homolytic reactions of C(60) with a
      number of perfluoroorganic and organomercury(II) compounds occurring under
      electron impact (EI) in the ionization chamber (IC) of a mass spectrometer could
      predict the reactivity of C(60) towards these compounds in solution or solid
      state. To expand the scope of this statement, C(60) and C(70) have been reacted
      with ketones RCOR(1), where R and R(1) are alkyl, aryl, benzyl, and CF(3), in an
      IC under EI to yield products of the addition of R(.) and R(1)(.) radicals to the
      fullerenes, paramagnetic ones being stabilized by hydrogen addition and loss.
      Experimental evidence in support of a mechanism involving homolytic dissociation
      of ketone molecules via superexcited states to afford these radicals that react
      with the fullerenes at the IC surface has been obtained. As anticipated, the
      reactions between C(60) and several ketones conducted in solution under UV
      irradiation have afforded Me-, Ph-, and CF(3)-derivatives of C(60). However, some
      other products have been identified by mass spectrometry and their formation is
      reasonably explained. When decalin has been employed as a solvent, decalinyl
      derivatives of the fullerene have been found among the products and the (9
      decalinyl)fullerenyl radical has been registered by EPR. Thus, incomplete but
      reasonable conformity of the results of the reactions of fullerenes with ketones
      in an IC under EI with those of the reactions of the same reagents in solution
      under UV irradiation has been demonstrated, and the former results can predict
      the latter ones to a reasonable extent.

PMID- 21952763
TI  - Mass spectrometry analysis of 2-nitrophenylhydrazine carboxy derivatized
      peptides.
AB  - Peptides with two or more basic residues, including those with post-translational
      modifications (PTMs), such as methylation and phosphorylation, can be highly
      hydrophilic and, therefore, are often difficult to be retained on a reversed
      phase (RP) column. In addition, these highly hydrophilic peptides may carry two
      or more positive charges, which often fragment poorly upon collisionally
      activated dissociation (CAD), resulting in few sequence-specific ions. C-terminal
      rearrangement may also occur during CAD. Furthermore, some PTMs are labile and
      tend to be lost when subjected to CAD as is the case with phosphorylation on
      serine or threonine. To overcome the difficulties of separation, detection, and
      fragmentation of highly hydrophilic peptides, we report here the effect of
      carboxy group derivatization with 2-nitrophenylhydrazine (this strategy will be
      called NPHylation for simplicity). NPHylation significantly increases the
      hydrophobicity of the peptides, eliminates C-terminal rearrangement in all cases,
      and offers enhanced sensitivity in some cases. In addition, the CAD spectra of
      the resulting NPHylated peptides carry more sequence-specific ions due to
      significant reduction of sequence scrambling as observed for peptide EHAGVISVL.
      Furthermore, the different carboxy derivatives of this peptide undergo sequence
      scrambling to varying degrees, which clearly demonstrates that the C-terminus has
      a profound effect on peptide fragmentation. Finally, sequence scrambling is a
      charge dependent phenomenon, which affects CAD of doubly charged peptides far
      more than their singly charged counterparts.

PMID- 21952764
TI  - Large carbon cluster anions generated by laser ablation of graphene.
AB  - The formation of large even-numbered carbon cluster anions, C(n)-, with n up to
      500 were observed in the mass spectra generated by laser ablation of graphene and
      graphene oxide, and the signal intensity of the latter is much weaker than that
      of the former. The cluster distributions generated from graphene can be readily
      altered by changing the laser energy and the accumulation period in the FT-ICR
      cell. By choosing suitable experimental conditions, weak signals of odd-numbered
      anions from C125- to C211-, doubly charged anions from C702- to C2302- and triply
      charged cluster anions from C803- to C2243- can be observed. Tandem MS was
      applied to some selected cluster anions. Though no fragment anions larger than
      C20- can be observed by the process of collisional activation with N(2) gas for
      most cluster ions, several cluster anions can lose units of C(2), C(4), C(6) or
      C(8) in their collision process. The differences in their dissociation kinetics
      and structures require further calculations and experimental studies.

PMID- 21952765
TI  - Mass spectrometry characterization of the thermal decomposition/digestion (TDD)
      at cysteine in peptides and proteins in the condensed phase.
AB  - We report on the characterization by mass spectrometry (MS) of a rapid,
      reagentless and site-specific cleavage at the N-terminus of the amino acid
      cysteine (C) in peptides and proteins induced by the thermal decomposition at 220
      250  degrees C for 10 s in solid samples. This thermally induced cleavage at C
      occurs under the same conditions and simultaneously to our previously reported
      thermally induced site-specific cleavage at the C-terminus of aspartic acid (D)
      (Zhang, S.; Basile, F. J. Proteome Res. 2007, 6, (5), 1700-1704). The C cleavage
      proceeds through cleavage of the nitrogen and alpha-carbon bond (N-terminus) of
      cysteine and produces modifications at the cleavage site with an amidation (-1
      Da) of the N-terminal thermal decomposition product and a -32 Da mass change of
      the C-terminal thermal decomposition product, the latter yielding either an
      alanine or beta-alanine residue at the N-terminus site. These modifications were
      confirmed by off-line thermal decomposition electrospray ionization (ESI)-MS,
      tandem MS (MS/MS) analyses and accurate mass measurements of standard peptides.
      Molecular oxygen was found to be required for the thermal decomposition and
      cleavage at C as it induced an initial cysteine thiol side chain oxidation to
      sulfinic acid. Similar to the thermally induced D cleavage, missed cleavages at C
      were also observed. The combined thermally induced digestion process at D and C,
      termed thermal decomposition/digestion (TDD), was observed on several model
      proteins tested under ambient conditions and the site-specificity of the method
      confirmed by MS/MS.

PMID- 21952766
TI  - Intriguing differences in the gas-phase dissociation behavior of protonated and
      deprotonated gonyautoxin epimers.
AB  - The aim of this study was to investigate the unusual gas-phase dissociation
      behavior of two epimer pairs of protonated gonyautoxins (GTX) following
      electrospray ionization in comparison to their deprotonated counterparts. The
      chemical structures of the investigated GTX1-4 variants vary in their
      substitution pattern at N-1 and the stereochemical orientation of the
      hydroxysulfate group at C-11 (11alpha for GTX1/2 versus 11beta for GTX3/4). The
      direct comparison of mass spectra in positive and negative ion modes illustrated
      two distinct features: first, an intriguing difference between protonated 11alpha
      and 11beta species, where 11alpha conformations exhibited almost complete
      dissociation of [M + H](+) ions via facile SO(3) elimination, while 11beta
      species remained mostly intact as [M + H](+); and second, the lack of such
      differences for the deprotonated counterparts. In this study, we propose an acid
      catalyzed elimination mechanism from density functional theory calculations,
      initiated by a proton transfer of a guanidinium proton to the hydroxysulfate
      group with simultaneous SO(3) release, which is only possible for the 11alpha
      conformation based on intramolecular distances. The same mechanism explains the
      lack of a comparable SO(3) loss in the negative ion mode. CID experiments
      supported this proposed mechanism for GTX1 and GTX2. Computational modeling of
      product ions seen in the CID spectra of GTX3 and GTX4 established that the lowest
      energy dissociation pathway for the 11beta epimers is elimination of water with
      the possibility for further SO(3) release from the intermediate product.
      Experimental data for structurally analogous decarbamoyl gonyautoxins confirmed
      the evidence for the GTX compounds as well as the proposed elimination
      mechanisms.

PMID- 21952767
TI  - Thermodynamics and mechanisms of protonated diglycine decomposition: a
      computational study.
AB  - We present a full computational description of the fragmentation reactions of
      protonated diglycine (H(+)GG). Relaxed potential energy surface scans performed
      at B3LYP/6-31 G(d) or B3LYP/6-311 + G(d,p) levels are used to map the reaction
      coordinate surfaces and identify the transition states (TSs) and intermediate
      reaction species for seven reactions observed experimentally in the succeeding
      companion paper. All structures are optimized at the B3LYP/6-311 + G(d,p) level,
      with single point energies of the key optimized structures calculated at B3LYP
      and MP2(full) levels using a 6-311 + G(2 d,2p) basis set. These theoretical
      structures and energies are compared with extensive calculations in the
      literature. Although the pathways elucidated here are generally in agreement with
      those previously outlined, new details and, for some reactions, lower energy
      transition states are located. Further, the mechanism for the combined loss of
      carbon monoxide and ammonia is explored for the first time.

PMID- 21952768
TI  - Thermodynamics and mechanisms of protonated diglycine decomposition: a guided ion
      beam study.
AB  - We present a full molecular description of fragmentation reactions of protonated
      diglycine (H(+)GG) by studying their collision-induced dissociation (CID) with Xe
      using a guided ion beam tandem mass spectrometer (GIBMS). Analysis of the kinetic
      energy-dependent CID cross sections provides the 0 K barriers for the sequential
      H(2)O+CO and CO+NH(3) losses from H(+)GG as well as for the reactions involved in
      y(1) and a(1) ion formation, after accounting for unimolecular decay rates,
      internal energy of reactant ions, and multiple ion-molecule collisions. Here,
      seven energetic barriers are measured for the fragmentation processes of H(+)GG,
      including the loss of H(2)O and of CO at ~140 and ~156 kJ/mol, the combined loss
      of (H(2)O+CO) and of (CO+NH(3)) at ~233 and ~185 kJ/mol, and formation of y(1)
      and a(1) ions at ~191 and ~212 kJ/mol, respectively, with a second channel for
      a(1) formation opening at ~326 kJ/mol. Theoretical energies from the preceding
      paper are compared with our experimental energies and found to be in good
      agreement. This validates the mechanisms explored computationally, including
      unambiguous identification of the b(2) ion as protonated 2-aminomethyl-5
      oxazolone, thereby allowing a complete characterization of the elementary steps
      of H(+)GG decomposition. These results also demonstrate that all reactive species
      are available from the ground state conformation, as opposed to involving an
      initial broad distribution of protonated conformers. This result verifies the
      utility of the "mobile proton" model for understanding the fragmentation of
      protonated proteins.

PMID- 21952769
TI  - Gas-phase coordination complexes of U(VI)O2(2+), Np(VI)O2(2+), and Pu(VI)O2(2+)
      with dimethylformamide.
AB  - Electrospray ionization of actinyl perchlorate solutions in H(2)O with 5% by
      volume of dimethylformamide (DMF) produced the isolatable gas-phase complexes,
      [An(VI)O(2)(DMF)(3)(H(2)O)](2+) and [An(VI)O(2)(DMF)(4)](2+), where An = U, Np,
      and Pu. Collision-induced dissociation confirmed the composition of the
      dipositive coordination complexes, and produced doubly- and singly-charged
      fragment ions. The fragmentation products reveal differences in underlying
      chemistries of uranyl, neptunyl, and plutonyl, including the lower stability of
      Np(VI) and Pu(VI) compared with U(VI).

PMID- 21952770
TI  - Imaging of phospholipids in formalin fixed rat brain sections by matrix assisted
      laser desorption/ionization mass spectrometry.
AB  - Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a
      valuable tool for the analysis of molecules directly from tissue. Imaging of
      phospholipids is gaining widespread interest, particularly as these lipids have
      been implicated in a variety of pathologic processes. Formalin fixation (FF) is
      the standard protocol used in histology laboratories worldwide to preserve tissue
      for analysis, in order to aid in the diagnosis and prognosis of diseases. This
      study assesses MALDI imaging of phospholipids directly in formalin fixed tissue,
      with a view to future analysis of archival tissue. This investigation proves the
      viability of MALDI-MSI for studying the distribution of lipids directly in
      formalin fixed tissue, without any pretreatment protocols. High quality molecular
      images for several phosphatidylcholine (PC) and sphingomyelin (SM) species are
      presented. Images correspond well with previously published data for the analysis
      of lipids directly from freshly prepared tissue. Different ionization pathways
      are observed when analyzing fixed tissue compared with fresh, and this change was
      found to be associated with formalin buffers employed in fixation protocols. The
      ability to analyze lipids directly from formalin fixed tissue opens up new doors
      in the investigation of disease profiles. Pathologic specimens taken for
      histologic investigation can be analyzed by MALDI-MS to provide greater
      information on the involvement of lipids in diseased tissue.

PMID- 21952771
TI  - Characterizing the intramolecular H-bond and secondary structure in methylated
      GlyGlyH+ with H2 predissociation spectroscopy.
AB  - We report vibrational predissociation spectra of the four protonated dipeptides
      derived from glycine and sarcosine, GlyGlyH(+)*(H(2))(1,2), GlySarH(+)*(D(2))(2),
      SarGlyH(+)*(H(2))(2), and SarSarH(+)*(D(2))(2), generated in a cryogenic ion
      trap. Sharp bands were recovered by monitoring photoevaporation of the weakly
      bound H(2) (D(2)) molecules in a linear action regime throughout the 700-4200 cm(
      1) range using a table-top laser system. The spectral patterns were analyzed in
      the context of the low energy structures obtained from electronic structure
      calculations. These results indicate that all four species are protonated on the
      N-terminus, and feature an intramolecular H-bond involving the amino group. The
      large blue-shift in the H-bonded N-H fundamental upon incorporation of a methyl
      group at the N-terminus indicates that this modification significantly lowers the
      strength of the intramolecular H-bond. Methylation at the amide nitrogen, on the
      other hand, induces a significant rotation (~110 degrees ) about the peptide
      backbone.

PMID- 21952772
TI  - A practical approach for determination of mass spectral baselines.
AB  - Precise determination of the baseline levels of mass spectra is critical for
      identification and quantification of analytes. Herein, we present a practical
      approach for determination of the baselines of mass spectra acquired under
      differential conditions. The baseline determined by this approach was the sum of
      baseline drift and noise level. The baseline drift was determined by averaging a
      number of lowest ion intensities. The noise level was determined based on the
      fact that an accelerated intensity change exists from noise to signal. This
      change was best revealed by the established accumulative layer thickness curve
      that was derived from the thicknesses of individual deducted layers. Deductions
      were performed sequentially layer by layer, each of which has a thickness of
      averaged lowest ion intensities from existing spectral data. The layer where the
      accelerated intensity change occurred was defined as a transition layer, which
      was determined from the polynomial regression in the sixth order of the
      accumulative layer thickness curve followed by resolving the roots of its fourth
      derivative. We validated the presence of this transition layer through
      determination of its convergence from various accumulative layer thickness curves
      generated by varying either the ending or the fineness of the sequential layer
      deductions. This simple, practical, program-based baseline determination approach
      should greatly increase the accuracy and consistency of identification and
      quantification by mass spectrometry, and facilitate the automation of data
      processing, thereby increasing the power of any high throughput methodology in
      general and of shotgun lipidomics in particular.

PMID- 21952773
TI  - Electrospray post-ionization mass spectrometry of electrosurgical aerosols.
AB  - The feasibility of electrospray (ES) ionization of aerosols generated by
      electrosurgical disintegration methods was investigated. Although electrosurgery
      itself was demonstrated to produce gaseous ions, post-ionization methods were
      implemented to enhance the ion yield, especially in those cases when the ion
      current produced by the applied electrosurgical method is not sufficient for MS
      analysis. Post-ionization was implemented by mounting an ES emitter onto a
      Venturi pump, which is used for ion transfer. The effect of various parameters
      including geometry, high voltage setting, flow parameters, and solvent
      composition was investigated in detail. Experimental setups were optimized
      accordingly. ES post-ionization was found to yield spectra similar to those
      obtained by the REIMS technique, featuring predominantly lipid-type species.
      Signal enhancement was 20- to 50-fold compared with electrosurgical
      disintegration in positive mode, while no improvement was observed in negative
      mode. ES post-ionization was also demonstrated to allow the detection of non
      lipid type species in the electrosurgical aerosol, including drug molecules.
      Since the tissue specificity of the MS data was preserved in the ES post
      ionization setup, feasibility of tissue identification was demonstrated using
      different electrosurgical methods.

PMID- 21952774
TI  - High throughput enzyme inhibitor screening by functionalized magnetic
      carbonaceous microspheres and graphene oxide-based MALDI-TOF-MS.
AB  - In this work, a high throughput methodology for screening enzyme inhibitors has
      been demonstrated by combining enzyme immobilized magnetic carbonaceous
      microspheres and matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF MS) with grapheme oxide as matrix. First, model enzyme
      acetylcholinesterase (AChE) was immobilized onto the 3
      glycidoxypropyltrimethoxysilane (GLYMO)-modified magnetic carbonaceous (MC)
      microspheres, displaying a high enzyme activity and stability, and also
      facilitating the separation of enzyme from substrate and product. The efficiency
      of immobilized AChE was monitored by biochemical assay, which was carried out by
      mixing enzyme-immobilized MC microspheres with model substrate acetylcholine
      (ACh), and subsequent quantitative determination of substrate ACh and product
      choline using graphene oxide-based MALDI-TOF-MS with no background inference. The
      limit of detection (LOD) for ACh was 0.25 fmol/MUL, and excellent linearity
      (R(2)=0.9998) was maintained over the range of 0.5 and 250 fmol/MUL. Choline was
      quantified over the range of 0.05 and 15 pmol/MUL, also with excellent linearity
      (R(2)=0.9994) and low LOD (0.15 fmol/MUL). Good accuracy and precision were
      obtained for all concentrations within the range of the standard curves. All
      together, eight compounds (four known AChE inhibitors and four control chemical
      compounds with no AChE inhibit effect) were tested with our promoted methodology,
      and the obtained results demonstrated that our high throughput screening
      methodology could be a great help to the routine enzyme inhibitor screening.

PMID- 21952775
TI  - Fragmentation reactions of b(5) and a (5) ions containing proline--the structures
      of a(5) ions.
AB  - A detailed study has been made of the b(5) and a(5) ions derived from the amides
      H-Ala-Ala-Ala-Ala-Pro-NH(2), H-Ala-Ala-Ala-Pro-Ala-NH(2), and H-Ala-Ala-Pro-Ala
      Ala-NH(2). From quasi-MS(3) experiments it is shown that the product ion mass
      spectra of the three b(5) ions are essentially identical, indicating
      macrocyclization/reopening to produce a common mixture of intermediates prior to
      fragmentation. This is in agreement with numerous recent studies of sequence
      scrambling in b ions. By contrast, the product ion mass spectra for the a(5) ions
      show substantial differences, indicating significant differences in the mixture
      of structures undergoing fragmentation for these three species. The results are
      interpreted in terms of a mixture of classical substituted iminium ions as well
      as protonated C-terminal amides formed by cyclization/rearrangement as reported
      recently for a(4) ions (Bythell, Maitre , Paizs, J . Am. Chem. Soc. 2010, 132,
      14761-14779). Novel fragment ions observed upon fragmentation of the a(5) ions
      are protonated H-Pro-NH(2) and H-Pro-Ala-NH(2) which arise by fragmentation of
      the amides. The observation of these products provides strong experimental
      evidence for the cyclization/rearrangement reaction to form amides and shows that
      it also applies to a(5) ions.

PMID- 21952777
TI  - Many overlapping peptides for protein hydrogen exchange experiments by the
      fragment separation-mass spectrometry method.
AB  - Measurement of the naturally occurring hydrogen exchange (HX) behavior of
      proteins can in principle provide highly resolved thermodynamic and kinetic
      information on protein structure, dynamics, and interactions. The HX fragment
      separation-mass spectrometry method (HX-MS) is able to measure hydrogen exchange
      in biologically important protein systems that are not accessible to NMR methods.
      In order to achieve high structural resolution in HX-MS experiments, it will be
      necessary to obtain many sequentially overlapping peptide fragments and be able
      to identify and analyze them efficiently and accurately by mass spectrometry.
      This paper describes operations which, when applied to four different proteins
      ranging in size from 140 to 908 residues, routinely provides hundreds of useful
      unique peptides, covering the entire protein length many times over. Coverage in
      terms of the average number of peptide fragments that span each amino acid
      exceeds 10. The ability to achieve these results required the integrated
      application of experimental methods that are described here and a computer
      analysis program, called ExMS, described in a following paper.

PMID- 21952776
TI  - Electron induced dissociation of singly deprotonated peptides.
AB  - Dissociation of singly charged species is more challenging compared with that of
      multiply charged precursor ions because singly charged ions are generally more
      stable. In collision activated dissociation (CAD), singly charged ions also gain
      less kinetic energy in a fixed electric field compared with multiply charged
      species. Furthermore, ion-electron and ion-ion reactions that frequently provide
      complementary and more extensive fragmentation compared with CAD typically
      require multiply charged precursor ions. Here, we investigate electron induced
      dissociation (EID) of singly deprotonated peptides and compare the EID
      fragmentation patterns with those observed in negative ion mode CAD.
      Fragmentation induced upon electron irradiation and collisional activation is not
      specific and results in the formation of a wide range of product ions, including
      b-, y-, a-, x-, c-, and z-type ions. Characteristic amino acid side chain losses
      are detected in both techniques. However, differences are also observed between
      EID and CAD spectra of the same species, including formation of odd-electron
      species not seen in CAD, in EID. Furthermore, EID frequently results in more
      extensive fragmentation compared with CAD. For modified peptides, EID resulted in
      retention of sulfonation and phosphorylation, allowing localization of the
      modification site. The observed differences are likely due to both vibrational
      and electronic excitation in EID, whereas only the former process occurs in CAD.

PMID- 21952778
TI  - ExMS: data analysis for HX-MS experiments.
AB  - A previous paper considered the problems that presently limit the hydrogen
      exchange-mass spectrometry (HX-MS) method for studying the biophysical and
      functional properties of proteins. Many of these problems can be overcome by
      obtaining and analyzing hundreds of sequentially overlapping peptide fragments
      that cover the protein many times over (Mayne et al. J. Am. Soc. Mass Spectrom.
      2011: 10.1007/s13361-011-0235-4). This paper describes a computer program called
      ExMS that furthers this advance by making it possible to efficiently process
      crowded mass spectra and definitively identify and characterize these many
      peptide fragments. ExMS automatically scans through high resolution MS data to
      find the individual isotopic peaks and isotopic envelopes of a list of peptides
      previously identified by MS/MS. It performs a number of tests to ensure correct
      identification in spite of peptide overlap in both chromatographic and mass
      spectrometric dimensions and possible multi-modal envelopes due to static or
      dynamic structural heterogeneity or HX EX1 behavior. The program can
      automatically process data from many sequential HX time points with no operator
      intervention at the rate of ~2 sec per peptide per HX time point using desktop
      computer equipment, but it also provides for rapid manual checking and decision
      when ambiguity exists. Additional subroutines can provide a step by step report
      of performance at each test along the way and parameter adjustment, deconvolute
      isotopic envelopes, and plot the time course of single and multi-modal H-D
      exchange. The program will be available on an open source basis at:
      http://HX2.med.upenn.edu/download.html.

PMID- 21952779
TI  - Evaluation of normalization methods on GeLC-MS/MS label-free spectral counting
      data to correct for variation during proteomic workflows.
AB  - Normalization of spectral counts (SpCs) in label-free shotgun proteomic
      approaches is important to achieve reliable relative quantification. Three
      different SpC normalization methods, total spectral count (TSpC) normalization,
      normalized spectral abundance factor (NSAF) normalization, and normalization to
      selected proteins (NSP) were evaluated based on their ability to correct for day
      to-day variation between gel-based sample preparation and chromatographic
      performance. Three spectral counting data sets obtained from the same biological
      conidia sample of the rice blast fungus Magnaporthe oryzae were analyzed by 1D
      gel and liquid chromatography-tandem mass spectrometry (GeLC-MS/MS). Equine
      myoglobin and chicken ovalbumin were spiked into the protein extracts prior to 1D
      SDS- PAGE as internal protein standards for NSP. The correlation between SpCs of
      the same proteins across the different data sets was investigated. We report that
      TSpC normalization and NSAF normalization yielded almost ideal slopes of unity
      for normalized SpC versus average normalized SpC plots, while NSP did not afford
      effective corrections of the unnormalized data. Furthermore, when utilizing TSpC
      normalization prior to relative protein quantification, t-testing and fold-change
      revealed the cutoff limits for determining real biological change to be a
      function of the absolute number of SpCs. For instance, we observed the variance
      decreased as the number of SpCs increased, which resulted in a higher propensity
      for detecting statistically significant, yet artificial, change for highly
      abundant proteins. Thus, we suggest applying higher confidence level and lower
      fold-change cutoffs for proteins with higher SpCs, rather than using a single
      criterion for the entire data set. By choosing appropriate cutoff values to
      maintain a constant false positive rate across different protein levels (i.e.,
      SpC levels), it is expected this will reduce the overall false negative rate,
      particularly for proteins with higher SpCs.

PMID- 21952780
TI  - Effects of select anions from the Hofmeister series on the gas-phase
      conformations of protein ions measured with traveling-wave ion mobility
      spectrometry/mass spectrometry.
AB  - The gas-phase conformations of ubiquitin, cytochrome c, lysozyme, and alpha
      lactalbumin ions, formed by electrospray ionization (ESI) from aqueous solutions
      containing 5 mM ammonium perchlorate, ammonium iodide, ammonium sulfate, ammonium
      chloride, ammonium thiocyanate, or guanidinium chloride, are examined using
      traveling-wave ion mobility spectrometry (TWIMS) coupled to time-of-flight (TOF)
      mass spectrometry (MS). For ubiquitin, cytochrome c, and alpha-lactalbumin,
      adduction of multiple acid molecules results in no significant conformational
      changes to the highest and lowest charge states formed from aqueous solutions,
      whereas the intermediate charge states become more compact. The transition to
      more compact conformers for the intermediate charge states occurs with fewer
      bound H(2)SO(4) molecules than HClO(4) or HI molecules, suggesting ion-ion or
      salt-bridge interactions are stabilizing more compact forms of the gaseous
      protein. However, the drift time distributions for protein ions of the same net
      charge with the highest levels of adduction of each acid are comparable,
      indicating that these protein ions all adopt similarly compact conformations or
      families of conformers. No significant change in conformation is observed upon
      the adduction of multiple acid molecules to charge states of lysozyme. These
      results show that the attachment of HClO(4), HI, or H(2)SO(4) to multiply
      protonated proteins can induce compact conformations in the resulting gas-phase
      protein ions. In contrast, differing Hofmeister effects are observed for the
      corresponding anions in solution at higher concentrations.

PMID- 21952781
TI  - Fullerenes, nanotubes, and graphite as matrices for collision mechanism in
      secondary ion mass spectrometry: determination of cyclodextrin.
AB  - A technique for improving the sensitivity of high mass molecular analysis is
      described. Three carbon species, fullerenes, single walled carbon nanotubes, and
      highly ordered pyrolytic graphite are introduced as matrices for the secondary
      ion mass spectrometry analysis of cyclodextrin (C(42)H(70)O(35), 1134 u). The
      fullerene and nanotubes are deposited as single deposition, and 10, 20, or 30
      deposition films and cyclodextrin is deposited on top. The cyclodextrin parent
      like ions and two fragments were analyzed. A 30 deposition fullerene film
      enhanced the intensity of cationized cyclodextrin with Na by a factor of 37.
      While the C(6)H(11)O(5) fragment, corresponding to one glucopyranose unit,
      increased by a factor of 16. Although fragmentation on fullerene is not
      suppressed, the intensity is twice as low as the parent-like ion. Deprotonated
      cyclodextrin increases by 100* and its C(8)H(7)O fragment by 10*. While the
      fullerene matrix enhances secondary ion emission, the nanotubes matrix film
      generates a basically constant yield. Graphite gives rise to lower intensity
      peaks than either fullerene or nanotubes. Scanning electron microscopy and atomic
      force microscopy provide images of the fullerene and nanotubes deposition films
      revealing flat and web structured surfaces, respectively. A "colliding ball"
      model is presented to provide a plausible physical mechanism of parent-like ion
      enhancement using the fullerene matrix.

PMID- 21952782
TI  - N-Protonated isomers as gateways to peptide ion fragmentation.
AB  - According to the popular "mobile proton model" for peptide ion fragmentation in
      tandem mass spectrometry, peptide bond cleavage is typically preceded by
      intramolecular proton transfer from basic sites to an amide nitrogen in the
      backbone. If the intrinsic barrier to dissociation is the same for all backbone
      sites, the fragmentation propensity at each amide bond should reflect the
      stability of the corresponding N-protonated isomer. This hypothesis was tested by
      using ab initio and force-field computations on several polyalanines and Leu
      enkephalin. The results agree acceptably with experimental reports, supporting
      the hypothesis. It was found that backbone N-protonation is most favorable near
      the C-terminus. The preference for C-terminal N-protonation, which is stronger
      for longer polyalanines, may be understood in terms of the well known "helix
      macrodipole" in the corresponding helical conformations. The opposite stability
      trend is found for peptides constrained to be linear, which is initially
      surprising but turns out to be consistent with the reversed direction of the
      macrodipole in the linear conformation.

PMID- 21952783
TI  - Electron transfer dissociation reveals changes in the cleavage frequencies of
      backbone bonds distant to amide-to-ester substitutions in polypeptides.
AB  - Interrogation of electron transfer dissociation (ETD) mass spectra of peptide
      amide-to-ester backbone bond substituted analogues (depsipeptides) reveals
      substantial differences in the entire backbone cleavage frequencies. It is
      suggested that the point permutation of backbone bonds leads to changes in the
      predominant ion structures by removal/weakening of specific hydrogen bonding. ETD
      responds to these changes by redistributing the cleavage frequencies of the
      peptide backbone bonds. In comparison, no distinction between depsi-/peptide was
      observed using collision-activated dissociation, which is consistent with a
      general unfolding and elimination of structural information of these ions. These
      results should encourage further exploration of depsipeptides for gas-phase
      structural characterization.

PMID- 21952784
TI  - Blackbody infrared radiative dissociation of protonated oligosaccharides.
AB  - The dissociation pathways, kinetics, and energetics of protonated
      oligosaccharides in the gas phase were investigated using blackbody infrared
      radiative dissociation (BIRD). Time-resolved BIRD measurements were performed on
      singly protonated ions of cellohexaose (Cel(6)), which is composed of beta-(1->4)
      linked glucopyranose rings, and five malto-oligosaccharides (Mal(x), where x=4
      8), which are composed of alpha-(1->4)-linked glucopyranose units. At the
      temperatures investigated (85-160  degrees C), the oligosaccharides dissociate at
      the glycosidic linkages or by the loss of a water molecule to produce B- or Y
      type ions. The Y ions dissociate to smaller Y or B ions, while the B ions yield
      exclusively smaller B ions. The sequential loss of water molecules from the
      smallest B ions (B(1) and B(2)) also occurs. Rate constants for dissociation of
      the protonated oligosaccharides and the corresponding Arrhenius activation
      parameters (E(a) and A) were determined. The E(a) and A-factors measured for
      protonated Mal(x) (x>4) are indistinguishable within error (~19 kcal mol(-1),
      10(10) s(-1)), which is consistent with the ions being in the rapid energy
      exchange limit. In contrast, the Arrhenius parameters for protonated Cel(6) (24
      kcal mol(-1), 10(12) s(-1)) are significantly larger. These results indicate that
      both the energy and entropy changes associated with the glycosidic bond cleavage
      are sensitive to the anomeric configuration. Based on the results of this study,
      it is proposed that formation of B and Y ions occurs through a common
      dissociation mechanism, with the position of the proton establishing whether a B
      or Y ion is formed upon glycosidic bond cleavage.

PMID- 21952785
TI  - Spectral accuracy and sulfur counting capabilities of the LTQ-FT-ICR and the LTQ
      Orbitrap XL for small molecule analysis.
AB  - Color Index Disperse Yellow 42 (DY42), a high-volume disperse dye for polyester,
      was used to compare the capabilities of the LTQ-Orbitrap XL and the LTQ-FT-ICR
      with respect to mass measurement accuracy (MMA), spectral accuracy, and sulfur
      counting. The results of this research will be used in the construction of a dye
      database for forensic purposes; the additional spectral information will increase
      the confidence in the identification of unknown dyes found in fibers at crime
      scenes. Initial LTQ-Orbitrap XL data showed MMAs greater than 3 ppm and poor
      spectral accuracy. Modification of several Orbitrap installation parameters
      (e.g., deflector voltage) resulted in a significant improvement of the data. The
      LTQ-FT-ICR and LTQ-Orbitrap XL (after installation parameters were modified)
      exhibited MMA <= 3 ppm, good spectral accuracy (chi(2) values for the isotopic
      distribution <= 2), and were correctly able to ascertain the number of sulfur
      atoms in the compound at all resolving powers investigated for AGC targets of
      5.00 * 10(5) and 1.00 * 10(6).

PMID- 21952786
TI  - Transition metal ions: charge carriers that mediate the electron capture
      dissociation pathways of peptides.
AB  - Electron capture dissociation (ECD) of model peptides adducted with first row
      divalent transition metal ions, including Mn(2+), Fe(2+), Co(2+), Ni(2+), Cu(2+),
      and Zn(2+), were investigated. Model peptides with general sequence of ZGGGXGGGZ
      were used as probes to unveil the ECD mechanism of metalated peptides, where X is
      either V or W; and Z is either R or N. Peptides metalated with different divalent
      transition metal ions were found to generate different ECD tandem mass spectra.
      ECD spectra of peptides metalated by Mn(2+) and Zn(2+) were similar to those
      generated by ECD of peptides adducted with alkaline earth metal ions. Series of c
      /z-type fragment ions with and without metal ions were observed. ECD of Fe(2+),
      Co(2+), and Ni(2+) adducted peptides yielded abundant metalated a-/y-type
      fragment ions; whereas ECD of Cu(2+) adducted peptides generated predominantly
      metalated b-/y-type fragment ions. From the present experimental results, it was
      postulated that electronic configuration of metal ions is an important factor in
      determining the ECD behavior of the metalated peptides. Due presumably to the
      stability of the electronic configuration, metal ions with fully-filled (i.e.,
      Zn(2+)) and half filled (i.e., Mn(2+)) d-orbitals might not capture the incoming
      electron. Dissociation of the metal ions adducted peptides would proceed through
      the usual ECD channel(s) via "hot-hydrogen" or "superbase" intermediates, to form
      series of c-/z(*)- fragments. For other transition metal ions studied, reduction
      of the metal ions might occur preferentially. The energy liberated by the metal
      ion reduction would provide enough internal energy to generate the "slow-heating"
      type of fragment ions, i.e., metalated a-/y- fragments and metalated b-/y-
      fragments.

PMID- 21952787
TI  - Discrimination between peptide O-sulfo- and O-phosphotyrosine residues by
      negative ion mode electrospray tandem mass spectrometry.
AB  - Unambiguous differentiation between isobaric sulfated and phosphorylated tyrosine
      residues (sTyr and pTyr) of proteins by mass spectrometry is challenging, even
      using high resolution mass spectrometers. Here we show that upon negative ion
      mode collision-induced dissociation (CID), pTyr- and sTyr-containing peptides
      exhibit entirely different modification-specific fragmentation patterns leading
      to a rapid discrimination between the isobaric covalent modifications using the
      tandem mass spectral data. This study reveals that the ratio between the relative
      abundances of [M-H-80](-) and [M-H-98](-) fragment ions in ion-trap CID and
      higher energy collision dissociation (HCD) spectra of singly deprotonated +80 Da
      Tyr-peptides can be used as a reliable indication of the Tyr modification group
      nature. For multiply deprotonated +80 Da Tyr-peptides, CID spectra of sTyr- and
      pTyr-containing sequences can be readily distinguished based on the
      presence/absence of the [M-nH-79]((n-1)-) and [M-nH-79-NL]((n-1)-) (n=2, 3)
      fragment ions (NL=neutral loss).

PMID- 21952788
TI  - Type and location of tumor-infiltrating macrophages and lymphatic vessels predict
      survival of colorectal cancer patients.
AB  - The type of tumor-infiltrating macrophages may be decisive in tumor immunity,
      lymphangiogenesis and in the clinical outcome of cancer. Here, we elucidated the
      prognostic significance of lymphatic vessels, different types of macrophages and
      the balance between different macrophage types in colorectal cancer. We analyzed
      the impact of density, type and location of macrophages on the clinical behavior
      of 159 primary colorectal carcinomas using CD68 as a pan-macrophage marker and
      CLEVER-1/Stabilin-1 as a marker for regulatory/suppressive macrophages.
      Podoplanin was used as a pan-lymphatic vessel marker. A high number of CLEVER
      1/Stabilin-1(+)  peritumoral macrophages positively correlated with survival (p =
      0.04). However, in more advanced disease (Stage IV), the patients with a high
      number of peritumoral or intratumoral CLEVER-1/Stabilin-1(+)  macrophages had a
      shorter disease-specific survival (p = 0.05, and p = 0.008, respectively).
      Moreover, a low number of suppressive intratumoral CLEVER-1/Stabilin-1(+) 
      macrophages among high numbers of CD68(+)  macrophages correlated with a low
      number of distant recurrences (p = 0.01) and to fewer disease relapses
      exclusively in the liver as well (p = 0.006). A high number of intratumoral
      lymphatics correlated with poor survival (p = 0.03). The results of this work
      suggest that the type of macrophages, number of lymphatic vessels and their
      location contribute to the clinical behavior of colorectal cancer in a disease
      stage-specific manner.

PMID- 21952789
TI  - The stability of rhythmic movement coordination depends on relative speed: the
      Bingham model supported.
AB  - Following many studies showing that the coupling in bimanual coordination can be
      perceptual, Bingham (Ecol Psychol in 16:45-53, 2001; 2004a, b) proposed a
      dynamical model of such movements. The model contains three key hypotheses: (1)
      Being able to produce stable coordinative movements is a function of the ability
      to perceive relative phase, (2) the information to perceive relative phase is
      relative direction of motion, and (3) the ability to resolve this information is
      conditioned by relative speed. The first two hypotheses have been well supported
      (Wilson and Bingham in Percept Psychophys 70:465-476, 2008; Wilson et al. in J
      Exp Psychol Hum 36:1508-1514, 2010a), but the third was not supported when tested
      by de Rugy et al. (Exp Brain Res 184:269-273, 2008) using a visual coordination
      task that required simultaneous control of both the amplitude and relative phase
      of movement. The purposes of the current study were to replicate this task with
      additional measures and to modify the original model to apply it to the new task.
      To do this, we conducted two experiments. First, we tested the ability to produce
      180 degrees  visual coordination at different frequencies to determine
      frequencies suitable for testing in the de Rugy et al. task. Second, we tested
      the de Rugy et al. task but included additional measures that yielded results
      different from those reported by de Rugy et al. These results were used to
      elaborate the original model. First, one of the phase-driven oscillators was
      replaced with a harmonic oscillator, so the resulting coupling was
      unidirectional. This change resulted in the model producing less stable 180
      degrees  coordination behavior beyond 1.5 Hz consistent with the results obtained
      in Experiment 1. Next, amplitude control and phase correction elements were added
      to the model. With these changes, the model reproduced behaviors observed in
      Experiment 2. The central finding was that the stability of rhythmic movement
      coordination does depend on relative speed and, thus, all three of the hypotheses
      contained in the original Bingham model are supported.

PMID- 21952790
TI  - Structural aspects and physiological consequences of APP/APLP trans-dimerization.
AB  - The amyloid precursor protein (APP) is one of the key proteins in Alzheimer's
      disease (AD), as it is the precursor of amyloid beta (Abeta) peptides
      accumulating in amyloid plaques. The processing of APP and the pathogenic
      features of especially Abeta oligomers have been analyzed in detail. Remarkably,
      there is accumulating evidence from cell biological and structural studies
      suggesting that APP and its mammalian homologs, the amyloid precursor-like
      proteins (APLP1 and APLP2), participate under physiological conditions via trans
      cellular dimerization in synaptogenesis. This offers the possibility that loss of
      synapses in AD might be partially explained by dysfunction of APP/APLPs cell
      adhesion properties. In this review, structural characteristics of APP trans
      cellular interaction will be placed critically in context with its putative
      physiological functions focusing on cell adhesion and synaptogenesis.

PMID- 21952791
TI  - Effects of experimentally induced low back pain on the sit-to-stand movement and
      electroencephalographic contingent negative variation.
AB  - It is becoming increasingly evident that people with chronic, recurrent low back
      pain (LBP) exhibit changes in cerebrocortical activity that associate with
      altered postural coordination, suggesting a need for a better understanding of
      how the experience of LBP alters postural coordination and cerebrocortical
      activity. To characterize changes in postural coordination and pre-movement
      cerebrocortical activity related to the experience of acutely induced LBP, 14
      healthy participants with no history of LBP performed sit-to-stand movements in 3
      sequential conditions: (1) without experimentally induced LBP; NoPain1, (2) with
      movement-associated LBP induced by electrocutaneous stimulation; Pain, and (3)
      again without induced LBP; NoPain2. The Pain condition elicited altered muscle
      activation and redistributed forces under the seat and feet prior to movement,
      decreased peak vertical force exerted under the feet during weight transfer,
      longer movement times, as well as decreased and earlier peak hip extension.
      Stepwise regression models demonstrated that electroencephalographic amplitudes
      of contingent negative variation during the Pain condition significantly
      correlated with the participants' change in sit-to-stand measures between the
      NoPain1 and Pain conditions, as well as with the subsequent difference in sit-to
      stand measures between the NoPain1 and NoPain2 conditions. The results,
      therefore, identify the contingent negative variation as a correlate for the
      extent of an individual's LBP-related movement modifications and to the
      subsequent change in movement patterns from before to after the experience of
      acutely induced LBP, thereby providing a direction for future studies aimed to
      understand the neural mechanisms underlying the development of altered movement
      patterns with LBP.

PMID- 21952792
TI  - Phenotypic and genetic analyses of the Wisconsin Card Sort.
AB  - The present study assessed the factor structure and etiology of traditional
      perseverative and nonperseverative errors, and six narrowly defined errors that
      occur during the Wisconsin Card Sorting Task (WCST). A computer-administered
      version of the WCST, designed to maximize the variance in a nonclinical sample,
      was used. Phenotypic factor analysis and twin models were used to examine the
      structure and genetic and environmental etiology in 191 monozygotic and 165
      dizygotic adolescent twin pairs. Factor analysis did not support the traditional
      division of errors into perseverative and nonperseverative errors. Heritability
      of individual indices was small to moderate (a(2) = 0.10 - 0.42), with varying
      significance. Estimates of shared environment (c(2) = 0.00 - 0.14) were not
      significant. The best fitting multivariate genetic model had one genetic factor,
      with specific variance and covariance due to nonshared environmental influences.
      These results suggest that there are common underlying genetic influences on WCST
      indices, along with index-specific environmental variance that does not
      correspond to the traditional division between perseverative and nonperseverative
      errors.

PMID- 21952793
TI  - Comparison between Gelfoam packing and no packing after endoscopic sinus surgery
      in the same patients.
AB  - After functional endoscopic sinus surgery (FESS), nasal packing may be necessary
      and a packing material which has benefits in both cost and efficacy would be
      required. This study aimed to determine the efficacy of Gelfoam packing on
      hemostasis and wound healing after FESS. Patients who underwent bilateral FESS
      due to chronic bilateral rhinosinusitis were enrolled. Randomly, one side was
      selected for Gelfoam packing and the other side for no packing. Subjective
      symptoms and objective findings such as synechia, granulation, pus discharge,
      edema, stenosis, and crust were evaluated. A total of 21 patients (17 men and 4
      women; mean age 39.7 years ranging from 12 to 75 years) were included. There were
      no statistical significant differences between two groups regarding both
      subjective symptoms and objective findings during 4 months after surgery. Three
      patients had postoperative bleeding in the no packing side. Gelfoam packing may
      be recommendable in terms of efficacy and cost-benefit after FESS.

PMID- 21952794
TI  - Oriented collagen as a potential cochlear implant electrode surface coating to
      achieve directed neurite outgrowth.
AB  - In patients with severe to profound hearing loss, cochlear implants (CIs) are
      currently the only therapeutic option when the amplification with conventional
      hearing aids does no longer lead to a useful hearing experience. Despite its
      great success, there are patients in which benefit from these devices is rather
      limited. One reason may be a poor neuron-device interaction, where the electric
      fields generated by the electrode array excite a wide range of tonotopically
      organized spiral ganglion neurons at the cost of spatial resolution. Coating of
      CI electrodes to provide a welcoming environment combined with suitable surface
      chemistry (e.g. with neurotrophic factors) has been suggested to create a closer
      bioelectrical interface between the electrode array and the target tissue, which
      might lead to better spatial resolution, better frequency discrimination, and
      ultimately may improve speech perception in patients. Here we investigate the use
      of a collagen surface with a cholesteric banding structure, whose orientation can
      be systemically controlled as a guiding structure for neurite outgrowth. We
      demonstrate that spiral ganglion neurons survive on collagen-coated surfaces and
      display a directed neurite growth influenced by the direction of collagen fibril
      deposition. The majority of neurites grow parallel to the orientation direction
      of the collagen. We suggest collagen coating as a possible future option in CI
      technology to direct neurite outgrowth and improve hearing results for affected
      patients.

PMID- 21952795
TI  - Comparison of three techniques in pediatric tonsillectomy.
AB  - The objective of this study was to compare the thermal welding technique (TWT),
      classic dissection (CD) tonsillectomy and bipolar cautery dissection (BCD) for
      pediatric tonsillectomy. Three hundred and five consecutive children with chronic
      tonsillitis and/or upper airway obstruction were alternately assigned to the TWT,
      CD, or BCD tonsillectomy groups. Age, gender, operation time, intraoperative
      blood loss, early postoperative pain, time to regain normal diet, and extent of
      healing of the tonsillar fossa on the tenth postoperative day were evaluated. The
      rate of intraoperative blood loss was significantly lower in the thermal welding
      and BCD groups (p < 0.001). The difference between mean operative time of TWT and
      BCD groups was not statistically significant (p > 0.001). The difference between
      mean operative time of the two groups against cold dissection group was
      statistically significant (p < 0.001). No significant difference was found in the
      incidence of posttonsillectomy hemorrhage between the three patient groups (p >
      0.001). The mean pain score was 4.8 +/- 1.2 (median 5, range 4-6) in the TWT
      group, 8.3 +/- 1.3 (median 8, range 7-10) in the BCD group, and 5.1 +/- 1.2
      (median 5, range 4-7) in the CD group 6 h to 7 days post-surgery. The difference
      between mean pain score between TWT and CD was not statistically significant (p >
      0.001). The difference between mean pain score of the two groups against BCD
      group was statistically significant (p < 0.001). The results showed TWT as a new
      tonsillectomy technique with advantages such as shorter operation time and
      minimal intraoperative blood loss for children patient's post operative comfort.
      When we compared TWT with the cold dissection and bipolar cautery tonsillectomy,
      we found that TWT tonsillectomy offered an innovative new tonsillectomy method
      with significantly reduced blood loss and reduced surgical time and without any
      increase in the postoperative pain.

PMID- 21952797
TI  - EFIS-EJI supported events: courses, schools, symposia and meetings with a
      European flavour.

PMID- 21952798
TI  - Diversity and plasticity of mononuclear phagocytes.

PMID- 21952799
TI  - F4/80 and the related adhesion-GPCRs.
AB  - The F4/80 monoclonal antibody was first reported in this journal 30 years ago
      (Eur. J. Immunol. 1981. 11: 805-815). F4/80 has become a widely used marker for
      monocytes and many, but not all, tissue macrophages in the mouse. F4/80 is a
      member of the EGF-TM7 family of leukocyte plasma membrane heptahelical molecules,
      which includes CD97 and EMR2. This Viewpoint summarises current knowledge of the
      expression, structure and functions of the EGF-TM7 family, as part of a larger
      family of tissue adhesion-GPCRs.

PMID- 21952801
TI  - MicroRNAs and the resolution phase of inflammation in macrophages.
AB  - Toll-like receptors (TLRs) signal the presence of pathogens and tissue injury,
      triggering the inflammatory process in macrophages. The goal of inflammation is
      to resolve the injury and return the body to homeostasis. MicroRNAs are an
      important group of regulators of TLR signaling and several are induced by TLRs in
      macrophages. These TLR-induced microRNAs target signaling components in the TLR
      pathway, thereby producing a negative feedback loop, and they are therefore prime
      candidates for the initiation of repair. Importantly, their dysregualtion may be
      important for chronic inflammation, which in turn can lead to autoimmunity and
      cancer, as discussed in this Viewpoint.

PMID- 21952800
TI  - Inflammatory signaling in macrophages: transitions from acute to tolerant and
      alternative activation states.
AB  - Acute inflammatory activation of macrophages by Toll-like and related receptors
      is characterized by transient activation of MAPK-, NF-kappaB- and IRF-mediated
      signaling pathways and expression of pro-inflammatory genes. This activation
      state is inherently unstable and often transitions into a state of 'tolerance'
      characterized by diminished signaling, repressive chromatin modifications, and an
      alternative gene expression program. This Viewpoint describes signaling and
      epigenetic mechanisms associated with transition to tolerant states, which are
      proposed to correspond to alternative activation states programmed by the
      original inflammatory stimuli.

PMID- 21952802
TI  - Transcriptional control of macrophage diversity and specialization.
AB  - The key driving force underlying cell identity is represented by the complex and
      dynamic interplay between cell-intrinsic, lineage-restricted developmental
      pathways on the one hand, and cell-extrinsic, tissue-specific microenvironmental
      signals on the other. In this context, macrophages are a paradigmatic cell
      population whose functional specialization in vivo reflects the impact of the
      local microenvironment on the intrinsic differentiation program, leading to a
      variety of specialized macrophage types in different tissues and conditions;
      however, how this is translated into a biological outcome is not appreciably
      understood. The kind of investigations described in this Viewpoint aim to explore
      the inner determinants of cell identity and functional diversification at a
      genomic level; mechanisms that permit plastic cell types, like macrophages, to
      adapt to different environments.

PMID- 21952803
TI  - Epigenetic control of macrophage polarization.
AB  - Epigenetic control of gene expression is critical for cellular differentiation
      and development. Macrophage development, polarization and activation are also
      controlled by DNA and histone modifications. This Viewpoint summarizes the recent
      findings on the role of histone modifications regulating macrophage polarization
      toward M1 and M2 subtypes.

PMID- 21952804
TI  - Intestinal macrophages - specialised adaptation to a unique environment.
AB  - Interest in intestinal mononuclear phagocytes (MPs), both DCs and macrophages
      (Mphis), has exploded in the recent years. In this Viewpoint we will detail how
      resident intestinal lamina propria (LP) Mphis possess distinctive properties that
      reflect adaptation to a unique microenvironment. They play quite different roles
      in the normal and inflamed mucosa and, as we will show, the existing paradigms of
      differentiated Mphi subsets and of 'resident' versus 'inflammatory' monocytes
      based on other tissues may not apply to the gut. Strategies for targeting Mphis
      as a means of dampening intestinal inflammation will need to take account of
      these unique characteristics.

PMID- 21952805
TI  - Regulatory macrophages: setting the threshold for therapy.
AB  - Macrophages exhibit remarkable plasticity and can change their phenotype in
      response to different environmental cues. They can become activated to kill
      intracellular microbes or they can assume regulatory properties to modulate
      immune responses. Regulatory macrophages are fundamentally different from
      classically activated, and we propose from non-classically activated macrophages;
      they arise in response to different stimuli and perform different physiological
      functions. They are likely to express unique biochemical markers that could be
      exploited to identify and potentially target these macrophage subsets in tissue.
      Furthermore, inducers of regulatory macrophages may have the potential to be used
      as anti-inflammatory therapeutics. Therefore, a better understanding of the
      various macrophage phenotypes may pave the way for new therapies that are
      directed at modulating macrophage functions or manipulating individual macrophage
      subsets.

PMID- 21952806
TI  - Macrophage heterogeneity and acute inflammation.
AB  - In this Viewpoint, we concentrate on the aspects of macrophage biology that we
      believe are fundamental for an appropriate contextual understanding of macrophage
      function during acute inflammation. These are the different origins of macrophage
      populations (and the implications of this for the renewal of these populations in
      the adult); and the impact of specific homeostatic or disease-associated
      microenvironments upon cellular heterogeneity, activation and effector functions.

PMID- 21952807
TI  - Macrophage activation governs schistosomiasis-induced inflammation and fibrosis.
AB  - Macrophages regulate the initiation, maintenance, and resolution of chronic
      inflammatory responses and their function depends on their activation status.
      Studies in mice infected with the helminth parasite Schistosoma mansoni have been
      particularly helpful in defining the in vivo function of classically and
      alternatively activated macrophages (AAMphis). These studies have shown that
      AAMphis protect mice from acute and chronic S. mansoni infection through distinct
      mechanisms, which are discussed in this Viewpoint.

PMID- 21952808
TI  - The role of macrophages and dendritic cells in the clearance of apoptotic cells
      in advanced atherosclerosis.
AB  - Accumulating evidence supports the notion that defective phagocytic clearance of
      dying cells, or defective "efferocytosis," is causally linked to the progression
      of advanced atherosclerosis. In advanced atherosclerotic lesions, defective
      efferocytosis leads to post-apoptotic necrosis, expansion of plaque necrotic
      cores, and susceptibility to atherothrombosis. Both macrophages and DC-like
      efferocytes are juxtaposed near expanding necrotic cores, where they engage
      apoptotic cells. In this Viewpoint, we discuss how reduced efferocytosis by
      macrophages and CD11c(HI)  DC-like cells may combine to reduce overall plaque
      stability and therefore promote susceptibility to acute atherothrombosis.

PMID- 21952809
TI  - Monocytes link atherosclerosis and cancer.
AB  - From many perspectives, cardiovascular diseases and cancers are fundamentally
      different. On the one hand, atherosclerosis is a disease of lipid accumulation
      driven by diet and lifestyle, whereas cancer is an attack "from within" driven by
      mutations. Nevertheless, studies over the past 20 years have forced us to re
      evaluate such a view. We are learning that, among other factors, the immune
      system is indispensable for the development and progression of both diseases. Its
      components are not only reactive but can also orchestrate both tumor and
      atherosclerotic lesion growth. In this Viewpoint, we explore how monocytes, which
      are key constituents of the immune system, forge links between cardiovascular
      diseases and cancers.

PMID- 21952810
TI  - Cancer-promoting tumor-associated macrophages: new vistas and open questions.
AB  - Tumor-associated macrophages (TAMs) are key components of the tumor
      macroenvironment. Cancer- and host cell-derived signals generally drive the
      functions of TAMs towards an M2-like polarized, tumor-propelling mode; however,
      when appropriately re-educated. TAMs also have the potential to elicit tumor
      destructive reactions. Here, we discuss recent advances regarding the
      immunobiology of TAMs and highlight open questions including the mechanisms of
      their accumulation (recruitment versus proliferation), their diversity and how to
      best therapeutically target these cells.

PMID- 21952811
TI  - Langerin, the "Catcher in the Rye": an important receptor for pathogens on
      Langerhans cells.
AB  - Langerhans cells (LCs) are a distinct subset of DCs that resides in the epidermis
      and other epithelia. They are potent antigen-presenting cells and strong inducers
      of T-cell responses. Like other DC types, LCs express C-type lectins that serve
      as antigen/pathogen uptake receptors, with Langerin/CD207 being the
      characteristic LC C-type lectin. In this issue of the European Journal of
      Immunology, Geijtenbeek and colleagues [Eur. J. Immunol. 2011. 41: 2619-2631]
      assign a role to Langerin on human LCs for binding and capturing measles virus.
      Interestingly, however, this function does not correlate with productive
      infection or with cross-presentation of measles virus. These authors show that
      measles virus does not infect the LCs via Langerin, and that LCs cannot cross
      present the virus to CD8(+)  T cells; however, presentation of this virus to
      CD4(+)  T cells occurs and is dependent on virus capture by Langerin. Thus, cross
      presentation of measles virus may be left to skin DCs other than LCs. This
      highlights the complexity of anti-viral T-cell responses that originate in the
      skin and also emphasizes the need for intensified investigations into human skin
      DCs in order to be able to ultimately harness their potential for immunotherapy.

PMID- 21952812
TI  - Memory lapses in graft-versus-host disease.
AB  - "Faster, better, more" is the conventional benchmark used to define responses of
      memory T cells when compared with their naive counterparts. In this issue of the
      European Journal of Immunology, Mark and Warren Shlomchik and colleagues [Eur. J.
      Immunol. 2011. 41: 2782-2792] make the intriguing observation that murine memory
      CD4(+)  T-cell populations enriched for alloreactive precursors are fully capable
      of rejecting allogeneic skin grafts but yet are incapable of inducing significant
      graft-versus-host disease. These observations add to the emerging concept that
      memory CD4(+)  T-cell development is more nuanced and complex than predicted by
      conventional models. In particular, the data suggest that it may be just as
      important to consider what naive or effector cells have "lost" in their
      transition to memory.

PMID- 21952813
TI  - Revisiting the protective and pathogenic roles of neutrophils: Ly-6G is key!
AB  - The physiological and pathophysiological roles of neutrophils in immune
      homeostasis and disease have been investigated extensively by way of anti-Gr-1
      mAb-mediated depletion experiments; however, the ability of the anti-Gr-1 mAb to
      specifically deplete neutrophils has long been questioned and it is now known
      that this mAb, which binds Ly6C and Ly6G, is also able to deplete monocytes and
      subsets of CD8(+)  T cells. This, therefore, casts doubt on the previous
      conclusions regarding the role of neutrophils drawn from studies using this mAb.
      Another mAb, which targets Ly6G only, has recently been shown to deplete
      neutrophils specifically and a study by Carr et al. (Eur. J. Immunol. 2011. 41:
      2666-2676) in this issue of the European Journal of Immunology utilizes this Ly
      6G mAb to reveal the precise role of neutrophils during Listeria monocytogenes
      (LM) infection. Carr et al. find that monocytes/macrophages, rather than
      neutrophils, dominate the initial control of LM growth in the spleen, whereas
      neutrophils in the liver are key for host resistance to LM infection. These data
      suggest that the previously reported protective or pathogenic roles of
      neutrophils in disease models need to be reconsidered through anti-Ly6G mAb
      mediated depletion experiments.

PMID- 21952814
TI  - T helper cell populations: as flexible as the skin?
AB  - T helper cells can be defined by the cytokines they produce and are divided into
      Th1, Th2, Th17, T(FH)  or regulatory T cells. Th17 cells have been shown to
      produce, in addition to IL-17, IL-22. In the current issue of the European
      Journal of Immunology, an article by Larsen et al. (Eur. J. Immunol. 2011. 41:
      2596-2605) provides evidence that human T helper cells, like murine cells, can
      also express IL-22 in the absence of the other T helper cell signature cytokines.
      Moreover, they show that these IL-22-producing cells, namely Th22 cells, can be
      found in the skin of psoriasis patients, where they might contribute to the
      pathogenesis of this inflammatory skin disease. Finally, they show that,
      molecularly, Th22 cells are related to Th17 cells, and might therefore be derived
      from the latter. In this Commentary, the development of the pro-inflammatory T
      helper populations in the skin are discussed and a model that explains the
      development of Th22 cells found in the skin of psoriasis patients is proposed.

PMID- 21952818
TI  - Regioselective and stereoselective cyclizations of cyclohexadienones tethered to
      active methylene groups.
AB  - The cyclization of 2,5-cyclohexadienones tethered to activated methylene groups
      was studied. The substitution around the cyclohexadienone ring serves to
      regioselectively direct these cyclizations based primarily on electronic effects.
      In the case of brominated substrates, these reactions proceed to give highly
      unusual electron-deficient tricyclic cyclopropanes. By using a Cinchona alkaloid
      based phase-transfer catalyst, prochiral cyclohexadienones can be desymmetrized
      with moderate stereoselectivity.

PMID- 21952819
TI  - Direct evidence of redox interaction between metal ion and support oxide in
      Ce(0.98)Pd(0.02)O(2-delta) by a combined electrochemical and XPS study.
AB  - A combined electrochemical method and X-ray photo electron spectroscopy (XPS) has
      been utilized to understand the Pd(2+)/CeO(2) interaction in Ce(1-x)Pd(x)O(2
      delta) (x = 0.02). A constant positive potential (chronoamperometry) is applied
      to Ce(0.98)Pd(0.02)O(2-delta) working electrode which causes Ce(4+) to reduce to
      Ce(3+) to the extent of ~35%, while Pd remains in the +2 oxidation state.
      Electrochemically cycling this electrode between 0.0-1.2 V reverts back to the
      original state of the catalyst. This reversibility is attributed to the
      reversible reduction of Ce(4+) to Ce(3+) state. CeO(2) electrode with no metal
      component reduces to CeO(2-y) (y~0.4) after applying 1.2 V which is not
      reversible and the original composition of CeO(2) cannot be brought back in any
      electrochemical condition. During the electro-catalytic oxygen evolution reaction
      at a constant 1.2 V for 1000 s, Ce(0.98)Pd(0.02)O(2-delta) reaches a steady state
      composition with Pd in the +2 states and Ce(4+): Ce(3+) in the ratio of
      0.65:0.35. This composition can be denoted as Ce(4+)(0.63)Ce(3+)(0.35)Pd(0.02)O(2
      delta-y) (y~0.17). When pure CeO(2) is put under similar electrochemical
      condition, it never reaches the steady state composition and reduces almost to
      85%. Thus, Ce(0.98)Pd(0.02)O(2-delta) forms a stable electrode for the electro
      oxidation of H(2)O to O(2) unlike CeO(2) due to the metal support interaction.

PMID- 21952820
TI  - Joining carbon nanotubes.
AB  - To fully exploit the exceptional electronic and mechanical properties of carbon
      nanotubes in real-world applications, it is desirable to create carbon nanotube
      networks in which separate, multiple nanotubes are joined so that as many as
      possible of the properties of single nanotubes are conserved. In this review we
      summarize the progress made towards this goal, covering techniques including
      electron and ion beam irradiation, Joule heating and spark plasma sintering.

PMID- 21952821
TI  - Effect of antioxidant N-acetylcysteine on diabetic retinopathy and expression of
      VEGF and ICAM-1 from retinal blood vessels of diabetic rats.
AB  - Diabetic retinopathy (DR) is a leading cause of blindness globally and its
      pathogenesis has still not been completely elucidated. Some studies show a close
      relation between oxidative stress and DR. This study was aimed to investigate the
      effects of anti-oxidant in DR and expression of vascular endothelial growth
      factor (VEGF) and intercellular adhesion molecule-1 (ICAM-1) from retinal blood
      vessels in diabetic rats. Diabetic rat models were established by intraperitoneal
      injection of streptozotocin (60 mg/kg) and confirmation of high serum glucose
      levels in the animals. Antioxidant N-acetylcysteine was given to diabetic rats to
      elicit antioxidative responses, and rats were sacrificed at 3 and 5 months.
      Ultrastructures of retinal vascular tissues were observed under transmission
      electron microscope, and pathology of retinal capillaries was examined using
      retinal vascular digest preparations. Changes in the expression of VEGF and ICAM
      1 were examined by immunofluorescence; and reactive oxygen species contents in
      the retinas were detected using dichlorofluorescein assay. Compared with normal
      rats, diabetic rats displayed significant retinopathy both under electronic and
      light microscopy, accompanied by elevated reactive oxygen species contents in the
      retinas; N-acetylcysteine treatment alleviated the pathological changes and also
      decreased reactive oxygen species, most significantly at 5 months. VEGF and ICAM
      1 expressions were significantly up-regulated in retinal blood vessels from
      diabetic rats, and such up-regulation was attenuated by N-acetylcysteine
      treatment. The expression of both factors returned to basal levels after 5-month
      treatment with N-acetylcysteine. Long-term N-acetylcysteine treatment exerts
      protective effects on the diabetic retinas, possibly through its down-regulation
      of the expression of VEGF and ICAM-1, and reduction of reactive oxygen species
      content in retinal vascular tissues in diabetic rats.

PMID- 21952822
TI  - Role of microRNAs in endothelial inflammation and senescence.
AB  - The functionality of endothelial cells is fundamental for the homoeostasis of the
      vascular system. Increasing evidence shows that endothelial inflammation and
      senescence contribute greatly to multiple vascular diseases including
      atherosclerosis. However, little is known regarding the complex upstream
      regulators of gene expression and translation involved in these responses.
      MicroRNAs (miRNAs) have emerged as a novel class of endogenous, small, non-coding
      RNAs that negatively regulate over 30% of genes in a cell via degradation or
      translational inhibition of their target mRNAs. During the past few years, miRNAs
      have emerged as key regulators for endothelial biology and function. Endothelial
      inflammation is critically regulated by miRNAs such as miR-126 and miR-10a in
      vitro and in vivo. Endothelial aging is additionally controlled by miR-217 and
      miR-34a. In this review, we summarize the role of miRNAs and their target genes
      in endothelial inflammation and senescence, and discuss their applicability as
      drug targets.

PMID- 21952823
TI  - Involvement of SEPT4_i1 in hepatocellular carcinoma: SEPT4_i1 regulates
      susceptibility to apoptosis in hepatocellular carcinoma cells.
AB  - SEPT4 belongs to the Septin family with multiple functions in cell division,
      cytoskeletal organization and other processes. This study aims to investigate the
      relationship between SEPT4_i1 isoform and human hepatocellular carcinoma (HCC).
      We showed that over-expression of SEPT4_i1 in HCC cells was able to sensitize
      cells to serum starvation-induced apoptosis. By contrast, knockdown of SEPT4_i1
      expression in HCC cells was able to rescue cells from apoptosis induced by serum
      deprivation and to promote cell growth. Expressional analysis of SEPT4_i1 in
      tumor tissues further revealed that SEPT4_i1 was significantly down-regulated in
      human HCC tissues. Taken together, these data suggests a tumor suppressor role of
      SEPT4_i1 in HCC through regulating HCC cell apoptosis.

PMID- 21952824
TI  - Meta-analysis shows significant association of the TP53 Arg72Pro with ovarian
      cancer risk.
AB  - Growing bodies of studies have been conducted on the association of TP53 Arg72Pro
      polymorphism with susceptibility to ovarian cancer and have yielded conflicting
      results. Thus, a meta-analysis was performed to summarize the possible
      association. 18 case-control studies, including 2,193 ovarian cancer cases and
      5,175 controls were identified. The quality of the studies was assessed according
      to a predefined scale. The strength of the associations between TP53 Arg72Pro
      polymorphism and ovarian cancer was measured by crude odds ratios (ORs) with 95%
      confidence intervals (CIs). Overall, no significant association was found between
      TP53 Arg72Pro polymorphism and ovarian cancer risk when all studies pooled into
      the meta-analysis in all genetic model. In the subgroup analysis by ethnicity,
      still no association of this polymorphism with ovarian cancer risk was obtained
      for all comparison models. However, significantly decreased risks of ovarian
      cancer were found for Arg/Arg versus Arg/Pro+Pro/Pro (OR 0.84, 95% CI 0.74-0.96)
      when the analysis was restricted to high quality studies. Conversely, when it was
      restricted to low quality studies, significantly increased risks were observed
      for Arg/Arg versus Pro/Pro (OR 1.58, 95% CI 1.09-2.28) and Arg/Arg+Arg/Pro versus
      Pro/Pro: (OR 1.50, 95% CI 1.10-2.06), which might be spurious due to the poor
      design of these studies. In conclusion, this meta-analysis suggests that the Arg
      allele is at a moderately reduced risk for ovarian cancer and this polymorphism
      might protect against ovarian carcinogenesis.

PMID- 21952825
TI  - Characterization of splice variants of the genes encoding human mitochondrial HMG
      CoA lyase and HMG-CoA synthase, the main enzymes of the ketogenesis pathway.
AB  - The genes HMGCS2 and HMGCL encode the two main enzymes for ketone-body synthesis,
      mitochondrial HMG-CoA synthase and HMG-CoA lyase. Here, we identify and describe
      possible splice variants of these genes in human tissues. We detected an
      alternative transcript of HMGCS2 carrying a deletion of exon 4, and two
      alternative transcripts of HMGCL with deletions of exons 5 and 6, and exons 5, 6
      and 7, respectively. All splice variants maintained the reading frame. However,
      Western blot studies and overexpression measurements in eukaryotic or prokaryotic
      cell models did not reveal HL or mHS protein variants. Both genes showed a
      similar distribution of the inactive variants in different tissues. Surprisingly,
      the highest percentages were found in tissues where almost no ketone bodies are
      synthesized: heart, skeletal muscle and brain. Our results suggest that
      alternative splicing might coordinately block the two main enzymes of ketogenesis
      in specific human tissues.

PMID- 21952826
TI  - Tissue transglutaminase inhibits the TRPV5-dependent calcium transport in an N
      glycosylation-dependent manner.
AB  - Tissue transglutaminase (tTG) is a multifunctional Ca(2+)-dependent enzyme,
      catalyzing protein crosslinking. The transient receptor potential vanilloid
      (TRPV) family of cation channels was recently shown to contribute to the
      regulation of TG activities in keratinocytes and hence skin barrier formation. In
      kidney, where active transcellular Ca(2+) transport via TRPV5 predominates, the
      potential effect of tTG remains unknown. A multitude of factors regulate TRPV5,
      many secreted into the pro-urine and acting from the extracellular side. We
      detected tTG in mouse urine and in the apical medium of polarized cultures of
      rabbit connecting tubule and cortical collecting duct (CNT/CCD) cells.
      Extracellular application of tTG significantly reduced TRPV5 activity in human
      embryonic kidney cells transiently expressing the channel. Similarly, a strong
      inhibition of transepithelial Ca(2+) transport was observed after apical
      application of purified tTG to polarized rabbit CNT/CCD cells. Furthermore, tTG
      promoted the aggregation of the plasma membrane-associated fraction of TRPV5.
      Using patch clamp analysis, we observed a reduction in the pore diameter after
      tTG treatment, suggesting distinct structural changes in TRPV5 upon crosslinking
      by tTG. As N-linked glycosylation of TRPV5 is a key step in regulating channel
      function, we determined the effect of tTG in the N-glycosylation-deficient TRPV5
      mutant. In the absence of N-linked glycosylation, TRPV5 was insensitive to tTG.
      Taken together, these observations imply that tTG is a novel extracellular enzyme
      inhibiting the activity of TRPV5. The inhibition of TRPV5 occurs in an N
      glycosylation-dependent manner, signifying a common final pathway by which
      distinct extracellular factors regulate channel activity.

PMID- 21952827
TI  - Establishment of intestinal homeostasis during the neonatal period.
AB  - The intestinal mucosa faces the challenge of regulating the balance between
      immune tolerance towards commensal bacteria, environmental stimuli and food
      antigens on the one hand, and induction of efficient immune responses against
      invading pathogens on the other hand. This regulatory task is of critical
      importance to prevent inappropriate immune activation that may otherwise lead to
      chronic inflammation, tissue disruption and organ dysfunction. The most striking
      example for the efficacy of the adaptive nature of the intestinal mucosa is
      birth. Whereas the body surfaces are protected from environmental and microbial
      exposure during fetal life, bacterial colonization and contact with potent
      immunostimulatory substances start immediately after birth. In the present
      review, we summarize the current knowledge on the mechanisms underlying the
      transition of the intestinal mucosa during the neonatal period leading to the
      establishment of a stable, life-long host-microbial homeostasis. The
      environmental exposure and microbial colonization during the neonatal period, and
      also the influence of maternal milk on the immune protection of the mucosa and
      the role of antimicrobial peptides, are described. We further highlight the
      molecular mechanisms of innate immune tolerance in neonatal intestinal
      epithelium. Finally, we link the described immunoregulatory mechanisms to the
      increased susceptibility to inflammatory and infectious diseases during the
      neonatal period.

PMID- 21952828
TI  - Haploinsufficiency in mouse models of DNA repair deficiency: modifiers of
      penetrance.
AB  - Mouse models of DNA repair deficiency are useful tools for determining
      susceptibility to disease. Cancer predisposition and premature aging are commonly
      impacted by deficiencies in DNA repair, presumably as a function of reduced
      genomic fitness. In this review, a comprehensive analysis of all DNA repair
      mutant mouse models has been completed in order to assess the importance of
      haploinsufficiency for these genes. This analysis brings to light a clear role
      for haploinsufficiency in disease predisposition. Unfortunately, much of the data
      on heterozygous models are buried or underinvestigated. In light of a better
      understanding that the role of DNA repair haploinsufficiency may play in
      penetrance of other oncogenic or disease causing factors, it may be in the
      interest of human health and disease prevention to further investigate the
      phenotypes in many of these mouse models.

PMID- 21952829
TI  - Characteristic vibration patterns of odor compounds from bread-baking volatiles
      upon protein binding: density functional and ONIOM study and principal component
      analysis.
AB  - As the mechanism underlying the sense of smell is unclear, different models have
      been used to rationalize structure-odor relationships. To gain insight into
      odorant molecules from bread baking, binding energies and vibration spectra in
      the gas phase and in the protein environment [7-transmembrane helices (7TMHs) of
      rhodopsin] were calculated using density functional theory [B3LYP/6-311++G(d,p)]
      and ONIOM [B3LYP/6-311++G(d,p):PM3] methods. It was found that acetaldehyde
      ("acid" category) binds strongly in the large cavity inside the receptor, whereas
      2-ethyl-3-methylpyrazine ("roasted") binds weakly. Lys296, Tyr268, Thr118 and
      Ala117 were identified as key residues in the binding site. More emphasis was
      placed on how vibrational frequencies are shifted and intensities modified in the
      receptor protein environment. Principal component analysis (PCA) suggested that
      the frequency shifts of C-C stretching, CH(3) umbrella, C = O stretching and
      CH(3) stretching modes have a significant effect on odor quality. In fact, the
      frequency shifts of the C-C stretching and C = O stretching modes, as well as
      CH(3) umbrella and CH(3) symmetric stretching modes, exhibit different behaviors
      in the PCA loadings plot. A large frequency shift in the CH(3) symmetric
      stretching mode is associated with the sweet-roasted odor category and separates
      this from the acid odor category. A large frequency shift of the C-C stretching
      mode describes the roasted and oily-popcorn odor categories, and separates these
      from the buttery and acid odor categories.

PMID- 21952830
TI  - Notch in the kidney: development and disease.
AB  - Notch signalling is a highly conserved cell-cell communication mechanism that
      regulates development, tissue homeostasis, and repair. Within the kidney, Notch
      has an important function in orchestrating kidney development. Recent studies
      indicate that Notch plays a key role in establishing proximal epithelial fate
      during nephron segmentation as well as the differentiation of principal cells in
      the renal collecting system. Notch signalling is markedly reduced in the adult
      kidney; however, increased Notch signalling has been noted in both acute and
      chronic kidney injury. Increased glomerular epithelial Notch signalling has been
      associated with albuminuria and glomerulosclerosis, while tubular epithelial
      Notch activation caused fibrosis development most likely inducing an improper
      epithelial repair pathway. Recent studies thereby indicate that Notch is a key
      regulator of kidney development, repair, and injury.

PMID- 21952831
TI  - Abrogation of Cbl-PI3K interaction increases bone formation and osteoblast
      proliferation.
AB  - Cbl is an adaptor protein and E3 ligase that plays both positive and negative
      roles in several signaling pathways that affect various cellular functions.
      Tyrosine 737 is unique to Cbl and phosphorylated by Src family kinases.
      Phosphorylated CblY737 creates a binding site for the p85 regulatory subunit of
      phosphatidylinositol 3 kinase (PI3K) that also plays an important role in the
      regulation of bone homeostasis. To investigate the role of Cbl-PI3K interaction
      in bone homeostasis, we examined knock-in mice in which the PI3K binding site on
      Cbl was ablated due to the substitution of tyrosine 737 to phenylalanine
      (Cbl(YF/YF), YF mice). We previously reported that bone volume in these mice is
      increased due to decreased osteoclast function (Adapala et al., J Biol Chem
      285:36745-36758, 19). Here, we report that YF mice also have increased bone
      formation and osteoblast numbers. In ex vivo cultures bone marrow-derived YF
      osteoblasts showed increased Col1A expression and their proliferation was also
      significantly augmented. Moreover, proliferation of MC3T3-E1 cells was increased
      after treatment with conditioned medium generated by culturing YF bone marrow
      stromal cells. Expression of stromal derived factor-1 (SDF-1) was increased in YF
      bone marrow stromal cells compared to wild type. Increased immunostaining of SDF
      1 and CXCR4 was observed in YF bone marrow stromal cells compared to wild type.
      Treatment of YF condition medium with neutralizing anti-SDF-1 and anti-CXCR4
      antibodies attenuated MC3T3-E1 cell proliferation. Cumulatively, these results
      show that abrogation of Cbl-PI3K interaction perturbs bone homeostasis, affecting
      both osteoclast function and osteoblast proliferation.

PMID- 21952832
TI  - Significant association between common polymorphisms in the aromatase gene
      CYP19A1 and bone mineral density in postmenopausal women.
AB  - 17beta-Estradiol is important in maintaining bone structure, and regulation of
      its synthesis plays an important role in the development of postmenopausal
      osteoporosis. We and others have demonstrated associations between variation in
      the CYP19A1 gene (encoding aromatase) and areal bone mineral density (aBMD)
      phenotypes in women. In the present study 33 tag polymorphisms were genotyped
      across the CYP19A1 gene in a population of 1,185 Caucasian postmenopausal women
      to test the association between sequence variations, total DXA hip aBMD, and
      circulating 17beta-estradiol levels. An in silico bioinformatics analysis was
      performed for single nucleotide polymorphisms (SNPs) associated with aBMD to
      identify putative functional effects, while linkage disequilibrium analysis of
      these SNPs was undertaken with previously published sequence variants. Five SNPs
      located in the central third of the gene were strongly associated with total-hip
      aBMD after adjustment for age (P = 0.006-0.013). A haplotype analysis of these
      five SNPs revealed an association between the haplotype C-G-G-G-C and increased
      aBMD (P = 0.008) and the haplotype A-A-A-A-A and a decreased aBMD (P = 0.021).
      The haplotype frequency was 9.0% for C-G-G-G-C and 15.4% for A-A-A-A-A, with the
      variation in mean total-hip aBMD explained by the haplotype analyses being 5% and
      7%, respectively. None of these polymorphisms was significantly associated with
      circulating 17beta-estradiol levels. In conclusion, common genetic variations
      within the CYP19A1 gene are significantly associated with aBMD in postmenopausal
      Caucasian women.

PMID- 21952833
TI  - Tidal lung recruitment and exhaled nitric oxide during coronary artery bypass
      grafting in patients with and without chronic obstructive pulmonary disease.
AB  - BACKGROUND: We studied the occurrence of intraoperative tidal alveolar
      recruitment/derecruitment, exhaled nitric oxide (eNO), and lung dysfunction in
      patients with and without chronic obstructive pulmonary disease (COPD) undergoing
      coronary artery bypass grafting (CABG). METHODS: We performed a prospective
      observational physiological study at a university hospital. Respiratory
      mechanics, shunt, and eNO were assessed in moderate COPD patients undergoing on
      pump (n = 12) and off-pump (n = 8) CABG and on-pump controls (n = 8) before
      sternotomy (baseline), after sternotomy and before cardiopulmonary bypass (CPB),
      and following CPB before and after chest closure. Respiratory system resistance
      (R (rs)), elastance (E (rs)), and stress index (to quantify tidal recruitment)
      were estimated using regression analysis. eNO was measured with
      chemiluminescence. RESULTS: Mechanical evidence of tidal
      recruitment/derecruitment (stress index <1.0) was observed in all patients, with
      stress index <0.8 in 29% of measurements. Rrs in on-pump COPD was larger than in
      controls (p < 0.05). Ers increased in controls from baseline to end of surgery
      (19.4 +/- 5.5 to 27.0 +/- 8.5 ml cm H(2)O(-1), p < 0.01), associated with
      increased shunt (p < 0.05). Neither Ers nor shunt increased significantly in the
      COPD on-pump group. eNO was comparable in the control (11.7 +/- 7.0 ppb) and COPD
      on-pump (9.9 +/- 6.8 ppb) groups at baseline, and decreased similarly by 29% at
      end of surgery(p < 0.05). Changes in eNO were not correlated to changes in lung
      function. CONCLUSIONS: Tidal recruitment/derecruitment occurs frequently during
      CABG and represents a risk for ventilator-associated lung injury. eNO changes are
      consistent with small airway injury, including that from tidal recruitment
      injury. However, those changes are not correlated with respiratory dysfunction.
      Controls have higher susceptibility to develop complete lung derecruitment.

PMID- 21952834
TI  - Meta-analysis of laparoscopy-assisted distal gastrectomy with D2 lymph node
      dissection for gastric cancer.
AB  - BACKGROUND: To assess the value of laparoscopy-assisted distal gastrectomy with
      D2 dissection for treatment of gastric cancer. METHODS: We collected studies that
      have compared laparoscopy-assisted distal gastrectomy (LADG) and open distal
      gastrectomy (ODG) with D2 dissection for treatment of gastric cancer in the past
      15 years. Data of interest for LADG and ODG were subjected to meta-analysis using
      a fixed-effect and random-effect model. RESULTS: We analyzed 8 studies that
      included 1,065 patients. There were significant differences in operating time,
      blood loss, time to first flatus and first eating, postoperative hospital stay,
      and postoperative complications between the LADG and ODG groups. Compared with
      the ODG group, blood loss and complications in the LADG group decreased, time to
      recovery of gastrointestinal function and hospitalization period were shorter,
      but operating time was longer. There were no significant differences in the
      number of harvested lymph nodes, mortality, and rate of recurrence between the
      groups. CONCLUSIONS: Compared with ODG, LADG with D2 dissection has the
      advantages of minimal invasion, faster recovery, and fewer complications, and it
      can achieve the same degree of radicality and short-term prognosis as ODG. The
      drawbacks are that the operating time is slightly longer and long-term prognosis
      is not clear.

PMID- 21952835
TI  - Mucormycosis in Mato Grosso, Brazil: a case reports, caused by Rhizopus
      microsporus var. oligosporus and Rhizopus microsporus var. rhizopodiformis.
AB  - We identified the etiological agents responsible for two fatal cases of
      rhinocerebral mucormycosis with the classical risk factor for uncontrolled type
      II diabetes mellitus. Their initial symptoms did not point immediately to the
      suspicion of mucormycosis. Case 1, caused by Rhizopus microsporus var.
      oligosporus, was a 52-year-old man who presented with a painful pimple on his
      nose, which evolved with swelling, erythema, and a central pustule on his right
      hemiface suspected to be cellulitis. After 7 days of antibiotic treatment, the
      patient worsened with signs of sepsis and the lesion evolved to necrosis
      involving all his right face. Case 2, caused by Rhizopus microsporus var.
      rhizopodiformis, was a 57-year-old woman placed on continuous therapy with
      azathioprine and corticoids after a renal transplant due to chronic arterial
      hypertension and uncontrolled type II diabetes mellitus. Because she was
      suspected to have sepsis, the patient was treated with broad-spectrum antibiotics
      and mechanical ventilation, yet she deteriorated. Because Candida spp. were
      isolated from urine and a BAL, she was treated with fluconazole for 10 days, then
      substituted by caspofungin. Two weeks later, she presented with exophthalmus of
      the left eye that was surrounded by a large inflammatory and necrotic area. Both
      patients were the diagnosed with mucormycosis via direct microscopy of necrotic
      material prior to their death.

PMID- 21952836
TI  - Hydroxyurea enhances post-fusion hyphal extension during sexual development in C.
      neoformans var. grubii.
AB  - Mating and sexual development in C. neoformans var. grubii strains of the H99
      background is often less robust than that laboratory generated isogenic C.
      neoformans var. neoformans strains in the JEC21 background. In Candida albicans
      and Saccharomyces serevisiae, slowing of DNA synthesis and engagement of the
      replication stress response, such as that caused by treatment with hydroxyurea
      (HU), induces filamentation and pseudohyphal growth, respectively. In this study,
      we investigated the effect of HU treatment on C. neoformans var. grubii
      morphogenesis. Treatment with HU did not induce filamentation of yeast cells
      either in liquid culture or on solid YPD or V8 agar. In the presence of the
      opposite mating partner, we observed early emergence of hyphae in the presence of
      HU. Semi-quantitative analysis of fusion using marked strains demonstrated that
      no significant enhancement of fusion in the presence of HU. Transfer of fusion
      colonies from crosses performed in the absence of HU to V8 + HU revealed enhanced
      hyphal growth in the presence of HU. Analysis of expression of the target of HU,
      ribonucleotide reductase, revealed that a phylogenetically divergent catalytic
      subunit is replication stress responsive in C. neoformans. These results suggest
      that induction of replication stress promotes post-fusion hyphal growth of C.
      neoformans var. grubii strains in the H99 background.

PMID- 21952838
TI  - Active and non-active large-area metal-molecules-metal junctions.
AB  - The study of charge transport processes through organic molecules by using
      molecular junctions has generated great attention in the last few years,
      partially triggered by the possibility of developing molecular electronic devices
      to be implemented somehow into current silicon-based technology. As experimental
      tools, a large variety of conceptually and geometrically different metal
      molecule(s)-metal junctions has been proposed. While the intrinsic conductivity
      of a molecule is still elusive, parameters crucial for molecular electronics have
      been extracted by using a variety of junctions. Significantly, the results
      extracted from molecular junctions and those obtained by the kinetic approach in
      supramolecular D-B-A systems are complementary. For the sake of a practical
      discussion, a distinction is made between "active junctions" and "non-active
      junctions". Active junctions are those aimed at switching the electrical response
      by an external stimulus acting "in situ" to modify the electronic structure of
      the molecular system. Non-active junctions are those aimed at studying different
      conduction regimes by incorporating molecules of different electronic structures.
      Depending on their geometry, the junctions can incorporate different numbers of
      molecules. Large area molecular junctions present two main advantages: (1) a
      simpler assembly, by requiring less sophisticated fabrication and (2) a higher
      versatility, relative to single molecule junctions, towards potential
      applications in organic electronics. The present chapter focuses on the
      fabrication of a variety of large-area molecular junctions and summarizes and
      compares the experimental results.

PMID- 21952837
TI  - The use of residual dipolar coupling in studying proteins by NMR.
AB  - The development of residual dipolar coupling (RDC) in protein NMR spectroscopy,
      over a decade ago, has become a useful and almost routine tool for accurate
      protein solution structure determination. RDCs provide orientation information of
      magnetic dipole-dipole interaction vectors within a common reference frame. Its
      measurement requires a nonisotropic orientation, through a direct or indirect
      magnetic field alignment, of the protein in solution. There has been recent
      progress in the developments of alignment methods to allow the measurement of RDC
      and of methods to analyze the resulting data. In this chapter we briefly go
      through the mathematical expressions for the RDC and common descriptions of the
      alignment tensor, which may be represented using either Saupe order or the
      principal order matrix. Then we review the latest developments in alignment
      media. In particular we looked at the lipid-compatible media that allow the
      measurement of RDCs for membrane proteins. Other methods including conservative
      surface residue mutation have been invented to obtain up to five orthogonal
      alignment tensors that provide a potential for de novo structure and dynamics
      study using RDCs exclusively. We then discuss approximations assumed in RDC
      interpretations and different views on dynamics uncovered from the RDC method. In
      addition to routine usage of RDCs in refining a single structure, novel
      applications such as ensemble refinement against RDCs have been implemented to
      represent protein structure and dynamics in solution. The RDC application also
      extends to the study of protein-substrate interaction as well as to solving
      quaternary structure of oligomer in equilibrium with a monomer, opening an avenue
      for RDCs in high-order protein structure determination.

PMID- 21952839
TI  - Frontiers of organic conductors and superconductors.
AB  - We review the development of conductive organic molecular assemblies including
      organic metals, superconductors, single component conductors, conductive films,
      conductors with a switching function, and new spin state (quantum spin liquid
      state). We emphasize the importance of the ionicity phase diagram for a variety
      of charge transfer systems to provide a strategy for the development of
      functional organic solids (Mott insulator, semiconductor, superconductor, metal,
      complex isomer, neutral-ionic system, alignment of chemical potentials, etc.).
      For organic (super)conductors, the electronic dimensionality of the solids is a
      key parameter and can be designed based on the self-aggregation ability of a
      molecule. We present characteristic structural and physical properties of organic
      superconductors.

PMID- 21952840
TI  - EPR spectroscopy in polymer science.
AB  - Synthetic polymers belong to the vast realm of soft matter and are one of the key
      types of materials to address societal needs at the beginning of the twenty-first
      century. Polymer science progressively addresses questions that deal with tuning
      mesoscopic and macroscopic structures and functions of polymers by understanding
      the effects that govern these systems on the nanoscopic level. EPR spectroscopy
      as a local, sensitive, and extremely specific magnetic resonance technique in
      many cases shows sensitivity on well-suited length- (0-10 nm) and time scales
      (MUs-ps) and can deliver unique information on structure, dynamics, and in
      particular function of polymeric systems. A short review of recent literature is
      given and the power of simple EPR methods, especially CW EPR performed on a low
      cost benchtop spectrometer, to elucidate complex polymeric materials is shown
      with specific examples from thermoresponsive polymer systems. These bear great
      potential in molecular transport and biomedical applications (e.g., drug
      delivery) and insights into interactions between carrier and small molecule are
      fundamental for designing and tuning these materials.

PMID- 21952841
TI  - Fluorous hydrosilylation.
AB  - In this review, we describe the papers and patents dealing with the fluorous
      biphasic system (FBS) hydrosilylation reactions reported to date. Despite the
      limited number of reports, the FBS hydrosilylation reaction has been extremely
      successful. In all cases fluorous monophosphines (either alkylic or
      perfluoroalkylsilyl-substituted derivatives of triphenylphosphine) have been
      employed as ligands to synthesize and inmobilize the metal catalysts (either
      rhodium(I) or gold(I) derivatives) in the fluorous solvent (including a fluorous
      ionic liquid). The hydrosilylation of alkenes, ketones and enones with fluorous
      rhodium analogs to the Wilkinson's catalyst [RhCl(PPh(3))(3)], have afforded high
      TON/TOF and a very efficient separation and recycling of the fluorous catalyst.
      Modification of the fluorous content and position of the fluorous tails in the
      aryl groups of the phosphines have allowed for further optimization of the
      process and a better recovery of the catalyst with minimal leaching of rhodium
      and fluorous ligand to the organic phase. Moreover, the use of the so-called
      second generation methods which eliminate the need of fluorous solvents by
      exploiting the temperature-dependent solubilities of fluorous catalysts in common
      organic solvents (thermomorphic properties) have permitted the use and separation
      of fluorous alkyl-phosphine rhodium catalysts in hydrosilylation reactions in
      conventional organic solvents. The addition of an insoluble fluorous support such
      as Teflon tape allowed for an exceptionally easy and efficient recovery of
      fluorous rhodium catalysts ("catalyst-on-a-tape") in the hydrosilylation of
      ketones. In the case of the FBS gold-catalyzed hydrosilylation of aldehydes, new
      fluorous gold catalysts with alkylic phosphines have led to an efficient
      separation and recycling of the gold catalysts although the TON/TOF are lower
      than in the rhodium-catalyzed hydrosilylation of alkenes and ketones. A detailed
      study of the non-fluorous gold-catalyzed version has helped to explain how this
      catalytic system could be improved.

PMID- 21952842
TI  - Molecular cages and capsules with functionalized inner surfaces.
AB  - Molecular containers enclose a well defined cavity in which an appropriate guest
      molecule can be included. The corresponding complexes are generally characterized
      by high kinetic stability. Thermodynamic stability can be rather low, however,
      because attractive interactions are largely missing between host and guest
      causing binding to be mainly due to entropic factors. This situation can be
      improved by distributing appropriate binding sites across the inner surface of a
      molecular container to which an included guest can bind. This approach, while
      being conceptually simple, is not straightforward since the incorporation of
      converging binding sites into a concave surface is difficult and usually requires
      receptors architectures that differ from those of conventional covalently
      assembled molecular containers. Therefore, the term molecular cage rather than
      molecular container is often more appropriate for such types of receptors. In
      this overview, a selection of cage-type receptors is presented whose inner cavity
      is functionalized with groups that can engage in directed interactions with an
      included guest. These receptors, classified according to the type of interaction
      responsible for guest binding, were chosen to illustrate effects of the inwardly
      directed binding sites on receptor affinity, selectivity, or other binding
      properties.

PMID- 21952843
TI  - Powder diffraction crystallography of molecular solids.
AB  - Many important crystalline solids cannot be prepared as single crystals of
      suitable size and quality for structural characterization by conventional single
      crystal X-ray diffraction techniques and can instead be prepared only as
      microcrystalline powders. However, recent advances in techniques for determining
      crystal structures directly from powder X-ray diffraction data have created a
      unique opportunity for establishing structural properties of such materials. This
      chapter surveys the applications of powder X-ray diffraction across various
      aspects of structural and materials chemistry, focusing mainly on the
      opportunities that have emerged in recent years for carrying out complete crystal
      structure determination from powder X-ray diffraction data and giving particular
      emphasis to the case of molecular crystal structures. The current scope and
      future potential of powder X-ray diffraction as a strategy for crystal structure
      determination are discussed, and examples of applications across several
      disciplines of materials chemistry are presented.

PMID- 21952844
TI  - Biotransformation and enzymatic reactions of synthetic pyrethroids in mammals.
AB  - Synthetic pyrethroids, a major insecticide group, are used worldwide for
      controlling indoor and agricultural pests. Extensive mammalian metabolism studies
      have been carried out since the late 1960s, and major metabolic reactions have
      been found to be oxidation of the acid or alcohol moiety, ester cleavage, and
      conjugation reactions. In addition, various conjugation reactions occur in
      mammals, forming hydrophilic and lipophilic conjugates. Pyrethroids are generally
      rapidly metabolized in mammals and completely excreted from the body in a short
      period. Human and laboratory animals share similar metabolic reactions for
      pyrethroids. Oxidation reactions in humans are mediated by several CYP isoforms.
      On the other hand, ester bonds of pyrethroids are hydrolyzed mainly by
      carboxylesterase(s).

PMID- 21952845
TI  - Synthetic and biological applications of fluorous reagents as phase tags.
AB  - The search for new and better techniques for the purification of organic
      compounds has made the recent emergence of fluorous chemistry in the field of
      organic synthesis possible. Using fluorous reagents as phase tags allows for the
      access of different synthetic routes, and this has been translated into a time
      reduction and higher simplicity compared to standard, nonfluorous procedures. The
      synthesis in fluorous phase of target molecules can be pursued in a parallel or
      combinatorial manner in order to access chemical libraries with structural and/or
      stereochemical diversity. The preparation of radiolabeled molecules also benefits
      from the advantages of fluorous synthesis. Finally, biochemical tools such as
      microarrays or proteomic techniques are improved by means of fluorous-tagged
      compounds.

PMID- 21952846
TI  - Chemical applications of fluorous reagents and scavengers.
AB  - Fluorous modified reagents and scavengers have been widely used in the synthesis
      of small molecules and small molecule libraries. This chapter highlights some of
      those applications based on type of transformation and reagent or scavenger.

PMID- 21952847
TI  - Biology of fluoro-organic compounds.
AB  - Investigations on diverse aspects of fluoro-organic compounds have rapidly
      increased during the past decades. Because natural sources of fluoro-organic
      compounds are extremely rare, the industrial synthesis of fluorinated organic
      compounds and production of fluorinated natural product derivatives have greatly
      expanded in recent years because of their increasing importance in the
      agrochemical and pharmaceutical industries. Due to structural complexity or
      instability, synthetic modification is often not possible, and various
      biofluorination strategies have been developed in recent years for applications
      in the anti-cancer, anti-viral and anti-infection fields. Despite the industrial
      importance of fluorinated compounds, there have been serious concerns worldwide
      over the levels and synthetic routes of certain fluorinated organic compounds, in
      particular perfluorinated chemicals (PFCs). PFCs are emerging and recalcitrant
      pollutants which are widely distributed in the environment and have been detected
      in humans and wildlife globally. PFCs have been demonstrated to be potentially
      carcinogenic, adversely affect the neuroendocrine and immune systems, and produce
      neurotoxicity, heptatotoxicity and endocrine disrupting effects in vertebrate
      animals. Here, we provide an overview of recent advances in our understanding of
      the biology of various fluoro-organic compounds and perspectives for new enzymes
      and metabolic pathways for bioremediation of these chemicals.

PMID- 21952848
TI  - Drug delivery by water-soluble organometallic cages.
AB  - Until recently, organometallic derivatives were generally viewed as moisture- and
      air-sensitive compounds, and consequently very challenging to synthesise and very
      demanding in terms of laboratory requirements (Schlenk techniques, dried solvent,
      glove box). However, an increasing number of stable, water-soluble organometallic
      compounds are now available, and organometallic chemistry in aqueous phase is a
      flourishing area of research. As such, coordination-driven self-assemblies using
      organometallic building blocks are compatible with water, thus opening new
      perspectives in bio-organometallic chemistry.This chapter gives a short history
      of coordination-driven self-assembly, with a special attention to organometallic
      metalla-cycles, especially those composed of half-sandwich complexes. These
      metalla-assemblies have been used as sensors, as anticancer agents, as well as
      drug carriers.

PMID- 21952849
TI  - Ecotoxicology of organofluorous compounds.
AB  - Organofluorous compounds have been developed for myriad purposes in a variety of
      fields, including manufacturing, industry, agriculture, and medicine. The
      widespread use and application of these compounds has led to increasing concern
      about their potential ecological toxicity, particularly because of the stability
      of the C-F bond, which can result in chemical persistence in the environment.
      This chapter reviews the chemical properties and ecotoxicology of four groups of
      organofluorous compounds: fluorinated refrigerants and propellants, per- and
      polyfluorinated compounds (PFCs), fluorinated pesticides, and fluoroquinolone
      antibiotics. These groups vary in their environmental fate and partitioning, but
      each raises concern in terms of ecological risk on both the regional and global
      scale, particularly those compounds with long environmental half-lives. Further
      research on the occurrence and toxicities of many of these compounds is needed
      for a more comprehensive understanding of their ecological effects.

PMID- 21952850
TI  - Fluorous hydrogenation.
AB  - The application of fluorous phosphine-modified catalysts for the hydrogenation of
      olefins is reviewed.

PMID- 21952851
TI  - PtI2-catalyzed tandem 3,3-rearrangement/Nazarov reaction of arylpropargylic
      esters: synthesis of indanone derivatives.
AB  - An efficient PtI(2)-catalyzed tandem reaction of arylpropargylic esters,
      involving 3,3-rearrangement and Nazarov reaction, has been developed to produce 3
      substituted and 3,3-disubstituted indanone derivatives. This approach provided a
      pathway to the synthesis of indanone skeletons in natural products.

PMID- 21952852
TI  - The Bambui Cohort Study of Aging (1997-2008).

PMID- 21952853
TI  - The Bambui Cohort Study of Aging: methodology and health profile of participants
      at baseline.
AB  - The cohort study was initiated in 1997 to investigate the incidence and
      predictors of health outcomes in an elderly population with low socio-economic
      level. The eligible population consisted of all 1,742 residents in Bambui, Minas
      Gerais State, Brazil, aged 60 years and over (1,606 participated). During 10
      years of follow-up, 641 participants died and 96 were lost, leading to 13,739
      person-years of observation. The baseline health profile of participants revealed
      a double burden of diseases with high prevalence of chronic non-transmissible
      diseases and widespread Trypanosoma cruzi infection. The most common health
      condition was hypertension (61.5%), followed by chronic knee or hand symptoms
      (43.6%), common mental disorders (38.5%), T. cruzi infection (38.1%), and
      insomnia (36.7%). In general, the baseline prevalence of mental symptoms and
      cardiovascular diseases or risk factors was comparable to those found in
      populations in high income countries.

PMID- 21952854
TI  - Predictors of 10-year hospital use in a community-dwelling population of
      Brazilian elderly: the Bambui Cohort Study of Aging.
AB  - We use data from a population-based cohort of elderly Brazilians to assess
      predictors of hospitalizations during ten years of follow-up. Participants were
      1,448 persons aged 60 years and over at baseline (1997). The outcome was self
      reported number of hospitalizations per year. Slightly more than a fifth (23%)
      experienced no hospitalizations during the 10 year follow-up. About 30% had 1-2
      events, 31% had between 3 and 7 events, and about 18% had 8 or more events during
      this time. Results of multivariable hurdle and Cox proportional hazards models
      showed that the risk of hospitalization was positively associated with male sex,
      increased age, chronic conditions, and visits to the doctors in the previous 12
      months. Underweight was a predictor of any hospitalization, while obesity was an
      inconsistent predictor of hospitalization.

PMID- 21952855
TI  - Trajectories of cognitive decline over 10 years in a Brazilian elderly
      population: the Bambui Cohort Study of Aging.
AB  - Few population-based studies have examined long term cognitive trajectory, and
      these studies were conducted in high income countries. We investigated the
      association of age, gender and education with 10-year cognitive trajectory in a
      well-defined population of elderly using data from the Bambui Cohort Study of
      Aging, in Brazil. Cognition was measured using the Mini- Mental State Examination
      (MMSE). Cohort members underwent annual follow-ups. This analysis was based on
      12,206 MMSE measurements from 1,461 (91%) baseline participants. We used mixed
      effects models to study MMSE as outcome. The key findings from this analysis are
      that women and people with a higher schooling level at baseline had high scores
      of MMSE, while older participants started off lower. Regarding cognitive decline,
      women, older people and those with a higher schooling level declined faster.

PMID- 21952856
TI  - Dyslipidemia and the risk of incident hypertension in a population of community
      dwelling Brazilian elderly: the Bambui Cohort Study of Aging.
AB  - This study aimed to examine the prognostic value of lipid parameters for incident
      hypertension in elderly living in a community. The study included 306 (81% from
      total) persons aged > 60 years who were free of hypertension and of
      cardiovascular diseases at the baseline survey of the Bambui Cohort Study of
      Aging. The cumulative incidence of hypertension over three years was 37.3%. The
      relative risk (RR) of incident hypertension decreased 0.92 for each unit of HDL
      cholesterol (95%CI: 0.86-0.99) independent of several potential confounding
      factors. Individuals with HDL-cholesterol in the top tercile (> 55 mg/dL) had a
      risk of hypertension halve that those in the bottom tercile (RR = 0.54; 95%CI:
      0.33-0.90). Other lipid parameters had no significant effect on the outcome. High
      HDL-cholesterol showed an independent protective effect on subsequent development
      of hypertension in the elderly.

PMID- 21952857
TI  - Predictors of 10-year mortality in a population of community-dwelling Brazilian
      elderly: the Bambui Cohort Study of Aging.
AB  - We used data on 1,399 participants aged 60 and over from the Bambui Cohort Study
      of Aging to examine predictors of mortality in a socioeconomically disadvantaged
      population. From 1997 to 2007, 599 participants died and 6.2% were lost to follow
      up, leading to 12,415 person-years (pyrs) of observation. The death rate was 48.3
      per 1,000 pyrs. Age (adjusted hazard ratio [HR] = 1.40), male gender (HR = 1.80),
      never married (HR = 1.78) or a widow (HR = 1.26), poor self-rated health (HR =
      1.31), inability to perform four or more activities of daily living (HR = 3.29),
      number of cardiovascular risk factors (HR = 1.51 for two and HR = 1.91 for three
      or more), Trypanosoma cruzi infection (HR = 1.27), and number of medications (HR
      = 1.06) were each significantly (p < 0.05) and independently associated with
      mortality. The Mini-Mental State Examination score showed a protective effect (HR
      = 0.96). Except T. cruzi infection, other predictors of mortality were highly
      consistent with those found in more affluent elderly populations.

PMID- 21952858
TI  - An anthropologic study on strategies for addressing health problems among the
      elderly in Bambui, Minas Gerais State, Brazil.
AB  - This paper explores the contribution of anthropological perspectives for
      clarifying the mechanisms through which socioeconomic circumstances influence the
      strategies developed by elderly for addressing their health problems in a small
      Brazilian city. Interviews with 20 key-informants explored the community's broad
      perception of the health situation of the elderly. Life histories collected from
      30 elderly women examined their own perception of their health status and their
      health strategies. Narratives converge in emphasising the important role played
      by financial factors in accessing health services and medication. Life histories
      also describe some damaging strategies resorted to by the elderly to deal with
      their lack of resources. Elderly women emphasize the crucial support they receive
      from their family and/or neighbours to overcome health problems. Thus, the issue
      of poverty is not only a matter of socioeconomic circumstances, but also the
      poverty of broader social networks.

PMID- 21952859
TI  - Balking blood pressure "control" by older persons of Bambui, Minas Gerais State,
      Brazil: an ethno-epidemiological inquiry.
AB  - This ethno-epidemiological inquiry aims to comprehend hypertension-related
      experiences in the elderly population of Bambui, in the State of Minas Gerais,
      Brazil. It combines ethnographic descriptions with statistical data. The
      subjective significance of factors associated with adequate arterial pressure
      control is explored. A baseline cohort of 26 people with hypertension, randomly
      selected from a total number of 1,494 residents over the age of 60, was
      interviewed utilizing signs, meanings and actions methodology. Multivariate
      analysis shows an association (p < 0.001) between female gender and monthly
      household income and treatment of hypertension and adequate blood pressure
      control. The number of doctor visits is associated with treatment but not with
      adequate blood pressure control. Conflicting cultural construction of "blood
      pressure problems" contributes to "non-adherence" to treatment. There is a fine
      line between blood pressure "control" and what is perceived as health
      professionals "controlling" patients' lives. Doctor-prescribed regimes are
      perceived as "prohibiting life's pleasures" and "controlling" personal liberty
      and free choice. Giving elderly people a voice regarding their social context can
      promote autonomy, well-being and happiness in later life.

PMID- 21952860
TI  - Satisfaction with the neighborhood environment and health in older elderly: cross
      sectional evidence from the Bambui Cohort Study of Aging.
AB  - In order to investigate the association between satisfaction with the
      neighborhood environment and self-rated health among older elderly, data from 814
      participants of the eleventh wave of the Bambui Cohort Study of Aging were
      analyzed using robust Poisson regression analyses. Those elderly with higher
      satisfaction with their neighborhoods (PR = 0.75; 95%CI: 0.63-0.87) were less
      likely to report worse self-rated health. The number of chronic diseases (two, PR
      = 1.69; 95%CI: 1.05-2.70, three or more, PR = 1.99, 95%CI: 1.27-3.13), difficulty
      in performing daily activities (PR = 1.51; 95%CI: 1.28-1.78), presence of
      depressive symptoms (PR = 1.68; 95%CI: 1.44-1.95) and frequency of leisure-time
      exercise in previous 90 days (less than once a week, PR =1.24; 95%CI: 1.03-1.50)
      were all positively and significantly associated with poor self-rated health.
      This study provided empirical evidence that satisfaction with the neighborhood
      environment was associated with the health of the older elderly. The findings
      further suggest the potential importance of including this indicator in analyses
      of place and health among the elderly.

PMID- 21952861
TI  - Energy expenditure through physical activity in a population of community
      dwelling Brazilian elderly: cross-sectional evidences from the Bambui Cohort
      Study of Aging.
AB  - The aim of this study was to estimate physical activity energy expenditure among
      older adults. The study comprised 1,585 residents in Bambui, Minas Gerais State,
      Brazil, aged > 60 years (91% of the town's total elderly), and examined the
      frequency and duration of 23 types of physical activity among them. Median energy
      expenditure was 975 MET.min/week (1,195.8 among men and 803.1 among women),
      declining significantly with age in both sexes. The prevalence of sedentary
      lifestyles (< 450 MET.min/week) was 31.2%. Unhurried walking accounted for about
      1/3 of total energy expenditure. Multivariate analysis based on ordinal logistic
      regression showed inverse associations between energy expenditure and age and
      hospitalizations in both sexes. Among men, inverse associations were observed
      with smoking, number of chronic diseases and number of medical appointments.
      These results emphasize the need for effective strategies to increase physical
      activity in older elderly, and underscore the high prevalence of walking in this
      group.

PMID- 21952862
TI  - Birth cohort differences in cardiovascular risk factors in a Brazilian population
      of older elderly: the Bambui Cohort Study of Aging (1997 and 2008).
AB  - The aim of this study was to investigate whether cohort differences exist in the
      prevalence of cardiovascular risk factors among older elderly from the Bambui
      Cohort Study of Aging. Participants were those aged 71-81 years at two points in
      time a decade apart: 457 in 1997 (earlier cohort) and 553 in 2008 (recent
      cohort). The prevalence of hypertension (PR = 1.27; 95%CI: 1.19-1.36) and of
      diabetes mellitus (PR = 1.39; 95%CI: 1.06-1.83) was higher in the recent cohort
      compared to the earlier one, regardless of sex. The recent cohort had a lower
      prevalence of smoking (PR = 0.58; 95%CI: 0.42-0.80), and lower total
      cholesterol/HDL cholesterol ratio level (PR = 0.85; 95%CI: 0.80-0.89). There was
      a 136% increase in the pharmacologic treatment of diabetes and a 56% increase in
      pharmacologic management of hypertension in 2008 in comparison with 1997.
      Overall, the number of cardiovascular risk factors in the recent cohort remained
      similar to that of the early cohort.

PMID- 21952863
TI  - Birth cohort differences in anthropometric measures in the older elderly: the
      Bambui Cohort Study of Aging (1997 and 2008).
AB  - The aim of this study was to evaluate the effect of birth cohort on nutritional
      status among older elderly (71-81 years old) from the Bambui Cohort Study of
      Aging, conducted in Brazil in 1997 and 2008. We compared the two birth cohorts-
      1916-1926 (older cohort) and 1927-1937 (recent cohort)--considering body mass
      index (BMI = weight/height2), waist circumference (WC) and prevalence of
      overweight (BMI 3 27 kg/m2). BMI (beta = 0.09, 95%CI: 0.04, 0.15) and prevalence
      of overweight (PR = 1.02; 95%CI: 1.01; 1.03) were higher in the recent cohort
      than the earlier cohort, regardless of sex and schooling. No difference was
      observed in WC. Stratified by sex, similar overall trends were observed for men,
      and WC was higher in the recent cohort. Among women there was no difference in
      BMI and overweight, but WC was lower in the recent cohort. The cohort effect was
      greater among older men and, in the near future, may result in greater prevalence
      of overweight in this group.

PMID- 21952864
TI  - Birth cohort differences in hypertension control in a Brazilian population of
      older elderly: the Bambui Cohort Study of Aging (1997 and 2008).
AB  - We examined for cohort differences in hypertension control between participants
      in the Bambui Cohort Study of Aging of aging born 1916-1926 and 1927-1937.
      Participants included hypertensive elderly aged 71-81 at baseline (n = 313) and
      at 11th wave follow up (n = 484). Prevalence of hypertension awareness (70.9% and
      81.2%, respectively), median medical appointments in previous 12 months (2 and 3,
      respectively) and antihypertensive drug use (74.4% and 90.7% respectively)
      increased significantly from older to younger cohort. However, prevalence of
      appropriately controlled hypertension among those treated (< 140/< 90 mmHg) was
      similar in both cohorts (44.6% and 40.1%, p = 0.255). Multivariate analysis
      returned schooling as the only factor independently associated with appropriately
      controlled hypertension. Despite increased medical appointments and drug use in
      the recent cohort, the prevalence of appropriately controlled hypertension
      remained as low as in the older cohort.

PMID- 21952865
TI  - Birth cohort differences in the use of medications in a Brazilian population of
      older elderly: the Bambui Cohort Study of Aging (1997 and 2008).
AB  - This study examined differences in the use of medications in two birth cohorts
      (born from 1916 to 1926 and from 1927 to 1937) among older elderly in the
      population-based cohort study in Bambui, Minas Gerais State, Brazil. The study
      used data on participants who were 71-81 years of age in the baseline survey in
      1997 (n = 492) and in the 11th wave, in 2008 (n = 620). The number of medications
      currently consumed (mean = 4.6 and 3.4, respectively) and prevalence of
      polypharmacy (46.6% and 29.1%, respectively) were higher in the more recent
      cohort as compared to the earlier one. These differences were independent of
      gender, age, schooling, number of medical visits in the previous 12 months, and
      number of chronic conditions. The more recent cohort showed significant
      differences in the use of psychoactive drugs, lipid modifying agents, drugs for
      diabetes, and antithrombotic agents, as well as changes in drugs used for
      arterial hypertension. In general, these changes are consistent with those
      observed in elderly populations in high-income countries.

PMID- 21952866
TI  - Birth cohort differences in physical functioning levels among elderly Brazilians:
      findings from the Bambui Cohort Study of Aging (1997-2008).
AB  - The aim of this study was to investigate the cohort differences in physical
      functioning levels among the older (cohort members born in 1916-1926 and in 1927
      1937) participants of the Bambui Cohort Study of Aging. The data came from
      participants aged 71-81 who took part at baseline in 1997 (n = 491) and in the
      11th wave in 2008 (n = 620). The physical functioning variables included the
      following self-reported measures: activities of daily living, the instrumental
      activities of daily living and mobility. Poisson regression analyses were used to
      investigate the cohort year differences in physical functioning levels. Overall,
      the young cohort (2008) showed better levels of physical functioning compared to
      the older cohort (1997) across all three measures of physical functioning used.

PMID- 21952867
TI  - Changes in serum zinc levels associated with giardiasis and dietary zinc intake
      in mice.
AB  - The association of giardiasis with the malabsorption of zinc remains
      controversial. This study investigated changes in serum zinc levels in Giardia
      infected mice subjected to different dietary zinc regimens. Thirty-five mice
      (strain C(3)H/H(e)J) were randomly categorized into two groups. The first group
      was inoculated with 5 * 10(6) Giardia trophozoites (n = 18), and the second group
      remained Giardia free (n = 17). Each group (Giardia infected and Giardia free)
      was randomly classified into three subgroups and given low (9 mg Zn/kg), normal
      (33 mg Zn/kg), and high levels (288 mg Zn/kg) of dietary zinc over a 2-week
      period for acclimation. Fourteen days post-Giardia infection, all of the mice
      were euthanized and blood samples were collected. The number of trophozoites was
      quantified (hematocytometer), and serum zinc levels were determined via atomic
      absorption spectrophotometry. Significant increases in the median weights were
      only found in the Giardia-free mice (p < 0.05). A higher final median weight was
      found in the Giardia-free group when compared with that of the Giardia-infected
      group given low dietary zinc (p = 0.013). In the Giardia-infected group with low
      dietary zinc, the geometric mean of trophozoites was 3,498 +/- 101 (SE) per
      milliliter. The Giardia-infected group had lower serum zinc levels than did the
      Giardia-free group with the high dietary zinc regimens (p < 0.05). Our results
      are consistent with studies among human populations, but further studies are
      required to elucidate the actual mechanism governing the zinc-giardiasis
      interaction.

PMID- 21952868
TI  - Chlorate ion mediated rutile to anatase reverse phase transformation in the TiO2
      nanosystem.
AB  - Rutile TiO(2) nanoneedles (8 nm * 100 nm) synthesized at room temperature by
      anodization in perchloric acid (pH < 1) are shown to undergo an interesting
      reverse phase transformation to anatase nanoparticles (8 nm) at 300  degrees C
      only if the chlorate ions are maintained in the ambient medium. When chlorate
      ions are removed by multiple washing, the rutile phase and the needle morphology
      are maintained. The mechanism of formation of the ion-stabilized solid and its
      thermal evolution is discussed.

PMID- 21952869
TI  - Social-emotional dysfunction after isolated right anterior insular infarction.

PMID- 21952870
TI  - Neurological disorders in Iraqi refugees in Jordan: data from the United Nations
      Refugee Assistance Information System.
AB  - The United Nations High Commissioner for Refugees (UNHCR) recognizes 43.7 million
      forcibly displaced persons and asylum seekers due to conflict and persecution
      worldwide. Neurological disorders have rarely been described in displaced persons
      but likely pose a significant burden of disease. We describe the disease spectrum
      and health service utilization of Iraqi refugees and asylum seekers with
      neurological disorders using an information system developed by the UNHCR.
      Neurological disorders were actively monitored among the 7,642 UNHCR-registered
      Iraqi refugees and asylum seekers who received health and humanitarian assistance
      using a pilot, centralized, database called the Refugee Assistance Information
      System (RAIS) in the Kingdom of Jordan in 2010. There were 122 neurological
      diagnoses reported in 1,328 refugees (mean age 41 years, 49% female, 10%
      disabled, 43% with pending resettlement applications) in 2,659 health visits,
      accounting for 17% of all refugees who sought health assistance in RAIS. Referral
      to a neurologist occurred in 178 cases (13.4%). The most frequent ICD-10
      neurological diagnoses were dorsalgia (back pain) (29.7% of individuals with
      neurological disorders), headache (13.1%), and epilepsy (12.6%). Approximately 1
      in 20 Iraqi refugees with a neurological diagnosis self-reported a history of
      torture, which was higher than Iraqi refugees without a history of torture
      [66/1,328 versus 196/6,314, odds ratio (OR) = 1.63, 95% confidence interval (CI)
      1.21-2.18]. Neurological disease affects a high proportion of Iraqi refugees,
      including victims of torture and the disabled. Refugees require dedicated care
      for treatment of neurological disease with a focus on pain disorders and
      epilepsy.

PMID- 21952872
TI  - Clinical heterogeneity and underlying pathophysiological mechanisms of lateral
      flexion of the trunk in Parkinson's disease.

PMID- 21952871
TI  - Difference in chronological changes of outcome measures between untreated and
      placebo-treated patients of spinal and bulbar muscular atrophy.
AB  - Spinal and bulbar muscular atrophy (SBMA) is an adult-onset, X-linked motor
      neuron disease characterized by muscle atrophy, weakness, and bulbar involvement.
      The aim of this study was to analyze the differential change of various outcome
      measures by comparing the progression of motor impairment in the two independent
      groups: placebo-treated group (PTG) and natural history group (NHG). For the PTG,
      we analyzed 99 patients who participated in a previous double-blind phase III
      clinical trial and received placebo. For the NHG, a total of 34 patients were
      followed with no specific treatment. The characteristics of both groups did not
      differ at baseline except for disease duration. Although the 6 min walk distance
      (6MWD) showed almost the same progression in both groups (-14.7 +/- 7.3 m in NHG,
      -14.0 +/- 4.7 m in PTG; NS), there was a significant difference of progression in
      the ALSFRS-R between the NHG and PTG (-1.18 +/- 0.38, -0.14 +/- 0.24; p = 0.03).
      A similar tendency was also seen in the subgroup analysis of the patients whose
      disease durations were less than 10 years. Although the relationship between the
      ALSFRS-R and 6MWD at week 48 was similar to that at baseline in the NHG, the
      slope of the regression at week 48 was significantly milder than at baseline in
      the PTG (p = 0.04). In conclusion, these two groups demonstrated a large
      difference in the chronological analysis of a motor function score, but showed
      similar changes in objective measures of walking capacity. These findings should
      be thoroughly considered when designing clinical trials for slowly progressive
      neurodegenerative diseases such as SBMA.

PMID- 21952873
TI  - Optical and electrical properties of colloidal (spherical Au)-(spinel ferrite
      nanorod) heterostructures.
AB  - We report here a simple synthetic route to Au-Fe(x)O(y) heterostructures in which
      spinel ferrite (Fe(x)O(y)) grows as a nanorod on a spherical gold (Au) seed. The
      large red shift in the plasmon resonance in the heterostructures could be
      explained by a dielectric effect (although we could not entirely exclude a
      contribution due to electron transfer from Au to defect states at the Au
      Fe(x)O(y) interface), while the magnetic properties of the Au-Fe(x)O(y)
      heterostructures were basically the same as those of the corresponding
      nanocrystals after Au leaching. In films of Au-Fe(x)O(y) heterostructures the
      electrical conductivity appeared to be mediated by the Au domains.

PMID- 21952874
TI  - Na+/H+ exchanger 1 gene expression in tissues of yellow chicken.
AB  - The Na(+)/H(+) exchanger 1 (NHE1) transmembrane protein regulates intracellular
      pH, cell survival, cell growth, cell differentiation and plays a critical role in
      the progression of some diseases, including the pathogenesis of J avian leukosis.
      The chicken is an ideal model to study the function of NHE1 because it has
      developed highly efficient Na(+)-absorptive mechanisms in its small and large
      intestines. To date, there has been no detailed expression analysis to determine
      NHE1 expression in various tissues of the chicken. We determined the mRNA and
      protein expression levels of avian NHE1 by real-time quantitative PCR and
      immunohistochemical analysis. NHE1 mRNA was detected in all chicken tissues
      examined. Protein expression levels varied widely among tissues and did not
      always correlate with mRNA expression. Determining the mRNA and protein of NHE1
      expression patterns in chicken should help to delineate the NHE1 role in
      different tissues and its contribution to physiological and pathological
      processes. These data provide the basis for examining the distinct function of
      chicken NHE1 compared with its mammalian counterpart.

PMID- 21952875
TI  - Positive selection and functional divergence after melanopsin gene duplication.
AB  - A newly discovered melanopsin gene (Opn4) encodes a member of the opsins,
      melanopsin. Two melanopsin genes, mammalian-like Opn4m and Xenopus-like Opn4x,
      have been described in nonmammalian vertebrates, but the underlying evolutionary
      mechanisms behind the duplication of melanopsin genes remain unclear. We
      conducted a comprehensive evolutionary analysis within a phylogenetic framework.
      In our phylogenetic tree, the duplication of Opn4m and Opn4x probably occurred
      prior to the emergence of vertebrates, and subsequently Opn4x disappeared in the
      lineages leading to mammalian species. Evolutionary analyses show strong
      purifying selection during melanopsin evolution. We also provide evidence that
      Opn4x underwent positive selection after the early gene duplication events. It
      has been indicated that functional divergence and altered functional constraints
      occurred between Opn4m and Opn4x duplicates with the identification of positively
      selected amino acids. Our findings highlight the evolutionary malleability in
      vertebrate melanopsin genes and provide a genetic basis for comparative studies
      of functional properties of these two melanopsins.

PMID- 21952876
TI  - Influence of eight unclassified missense variants of the MLH1 gene on Lynch
      syndrome susceptibility.
AB  - Missense mutations in MLH1 have frequently been detected in patients with Lynch
      syndrome, but their genetic significance has not been extensively assessed. In
      this study, we attempt to evaluate the etiological role of eight MLH1 missense
      variants. The variants were analyzed for their ability to affect MLH1 protein
      interaction with its partner PMS2 in vivo employing a yeast two-hybrid system. In
      addition, a SIFT (sorting intolerant from tolerant) algorithm was adopted to
      predict the effects of amino acid substitutions. Finally, scanning of mutations
      in a normal Chinese population and assay of the clinical characteristics have all
      been taken into account. Our results demonstrated that the MLH1 variants D485E
      and L653R cause functional alterations of the human MutLalpha complex
      significantly. The R265C, D304V, A586P, and R755S variants affect partial
      interaction. The remaining two variants, N38D and L559R, could be nonfunctional
      polymorphisms or might affect the mismatch repair system through other
      mechanisms.

PMID- 21952877
TI  - Polymorphism of the apolipoprotein B gene and association with plasma lipid and
      lipoprotein levels in the Mongolian Buryat.
AB  - Allele frequencies at six RFLP sites (Ins/Del, ApaLI, AluI, XbaI, MspI, and
      EcoRI) of the apolipoprotein B gene (APOB) and the relationship of genotypes with
      plasma lipid and lipoprotein levels in the Mongolian Buryat were investigated.
      Common alleles at these sites in 110 Buryat subjects were I, G, A-, X-, M+, and
      E+; the frequencies of 0.809-0.991 differed strikingly from those of a few Asians
      and most Europeans. Five unambiguous haplotypes of all sites were revealed at
      74%; haplotype IGA-X-M+E+ (000000) was the most frequent (67%), followed by IGA+X
      M+E+ (001000) (19%). The frequency constitution differed significantly from the
      Chinese, Malaysians, and Caucasians but resembled the Indians. No APOB
      polymorphisms were associated with cholesterol levels (total, HDL and LDL).
      Significant associations of genotypes were shown with the triglyceride level only
      at the AluI and XbaI sites. The lipid level of A-A+ females or X-X+ males was
      higher than that of A-A- females or X-X- males, respectively.

PMID- 21952878
TI  - Prion protein coding gene (PRNP) variability in sheep from Turkey and Iran.
AB  - This study was designed to analyze variation of ovine prion protein in sheep
      breeds in Iran and Turkey. A competitive approach was used to analyze the open
      reading frame (ORF) of the ovine PRNP gene using a total of 186 samples from five
      indigenous sheep breeds. The ARQ allele was found to be the predominant allele in
      five breeds. The ARR allele was not observed in homozygous combination among the
      11 genotypes found in the study. In addition, six other polymorphisms were
      indicated. These findings have great significance for estimating genetic
      variability in the PRNP gene with regard to Iranian and Turkish sheep. Since no
      information on the susceptibility of some genotypes identified in this study has
      been reported, no grouping was made on the basis of susceptibility.

PMID- 21952879
TI  - Association between left atrial size and measures of adiposity among normal
      adolescent boys.
AB  - Obesity (OB) in adults is associated with insulin resistance, hypertension, and
      left atrial (LA) enlargement. This study aimed to determine the association
      between LA size and (1) different components of the metabolic syndrome (body mass
      index [BMI], waist circumference [WC], insulin levels, lipid levels, and blood
      pressure), and (2) left ventricular (LV) diameters and diastolic function. Data
      were collected cross-sectionally from 142 healthy adolescent boys age 16.8 +/-
      2.0 years in 2009. Measurements of BMI, WC, blood pressure, lipid profile, and
      insulin were performed. Mode M, two-dimensional Doppler echocardiography was
      performed. Measurements of LA area, LV end diastolic diameter (EDD), end systolic
      diameter (ESD), posterior wall, interventricular septum (IVS), and shortening
      fraction were performed. Tisular Doppler of the diastolic mitral annular E wave
      (DTE) and A wave (DTA) and the ratio of maximal early diastolic filling wave
      velocity to maximal early diastolic myocardial velocity (E/e') were recorded. The
      study group included 38 OB boys (26.8%) and 32 overweight boys (22.5%).
      Significant univariate association was found between LA area and BMI (r = 0.61),
      WC (r = 0.56), systolic blood pressure (r = 0.21), insulinemia (r = 0.28), high
      density lipoprotein-cholesterol (HDL-C) (r = -0.24), triglycerides (r = 0.20),
      EDD (r = 0.25), LV posterior wall (r = 0.25), IVS (r = 0.25), DTE (r = 0.27), DTA
      (r = 0.30), and E/e' (r = -0.28). Multiple linear regression analysis showed that
      LA area was associated with BMI (B = 0.61; R (2) = 0.47) adjusted for confounding
      variables. In adolescents, BMI and WC were significantly associated with LA,
      suggesting that OB could be associated with LA enlargement as early as
      adolescence.

PMID- 21952882
TI  - Ion mobility-mass spectrometry reveals conformational changes in charge reduced
      multiprotein complexes.
AB  - Characterizing intact multiprotein complexes in terms of both their mass and size
      by ion mobility-mass spectrometry is becoming an increasingly important tool for
      structural biology. Furthermore, the charge states of intact protein complexes
      can dramatically influence the information content of gas-phase measurements
      performed. Specifically, protein complex charge state has a demonstrated
      influence upon the conformation, mass resolution, ion mobility resolution, and
      dissociation properties of protein assemblies upon collisional activation. Here
      we present the first comparison of charge-reduced multiprotein complexes
      generated by solution additives and gas-phase ion-neutral reaction chemistry.
      While the charge reduction mechanism for both methods is undoubtedly similar,
      significant gas-phase activation of the complex is required to reduce the charge
      of the assemblies generated using the solution additive strategy employed here.
      This activation step can act to unfold intact protein complexes, making the data
      difficult to correlate with solution-phase structures and topologies. We use ion
      mobility-mass spectrometry to chart such conformational effects for a range of
      multi-protein complexes, and demonstrate that approaches to reduce charge based
      on ion-neutral reaction chemistry in the gas-phase consistently produce protein
      assemblies having compact, 'native-like' geometries while the same molecules
      added in solution generate significantly unfolded gas-phase complexes having
      identical charge states.

PMID- 21952881
TI  - An electrostatic charge partitioning model for the dissociation of protein
      complexes in the gas phase.
AB  - Electrosprayed multi-protein complexes can be dissociated by collisional
      activation in the gas phase. Typically, these processes follow a mechanism
      whereby a single subunit gets ejected with a disproportionately high amount of
      charge relative to its mass. This asymmetric behavior suggests that the departing
      subunit undergoes some degree of unfolding prior to being separated from the
      residual complex. These structural changes occur concomitantly with charge
      (proton) transfer towards the subunit that is being unraveled. Charge
      accumulation takes place up to the point where the subunit loses physical contact
      with the residual complex. This work develops a simple electrostatic model for
      studying the relationship between conformational changes and charge enrichment
      during collisional activation. Folded subunits are described as spheres that
      carry continuum surface charge. The unfolded chain is envisioned as random coil
      bead string. Simulations are guided by the principle that the system will adopt
      the charge configuration with the lowest potential energy for any backbone
      conformation. A finite-difference gradient algorithm is used to determine the
      charge on each subunit throughout the dissociation process. Both dimeric and
      tetrameric protein complexes are investigated. The model reproduces the
      occurrence of asymmetric charge partitioning for dissociation events that are
      preceded by subunit unfolding. Quantitative comparisons of experimental MS/MS
      data with model predictions yield estimates of the structural changes that occur
      during collisional activation. Our findings suggest that subunit separation can
      occur over a wide range of scission point structures that correspond to different
      degrees of unfolding.

PMID- 21952883
TI  - A new ion source and procedures for atmospheric pressure-electron capture
      dissociation of peptides.
AB  - We introduce a new atmospheric pressure-electron capture dissociation (AP-ECD)
      source in which conventional nanospray emitters are coupled with the source block
      and photoionization lamp of a PhotoSpray APPI source. We also introduce
      procedures for data collection and processing, aimed at maximizing the signal-to
      background ratio of ECD products. Representative data from Substance P are
      presented to demonstrate the performance of the technique. Further, we
      demonstrate the effects of two important experimental variables, source
      temperature and vacuum-interface declustering potential (DP), on the method.
      Last, we show that even when a high source temperature is used to maximize
      efficiency, AP-ECD fragments of a model phosphorylated peptide retain the
      modification.

PMID- 21952884
TI  - Evidence of molecular fragmentation inside the charged droplets produced by
      electrospray process.
AB  - The behavior of the analyte molecules inside the neutral core of the charged
      droplet produced by the electrospray (ES) process is not unambiguously known to
      date. We have identified interesting molecular transformations of two suitably
      chosen analytes inside the ES droplets. The highly stable Ni(II) complex of 1,8
      dimethyl-1,3,6,8,10,13-hexaazacyclotetradecane (1) that consists of a positive
      charge at the metal center, and the allyl pendant armed tertiary amine containing
      macrocycle 3,4,5:12,13,14-dipyridine-2,6,11,15-tetramethyl-1,7,10,16-tetraallyl
      1,4,7,10,13,16-hexaazacyclooctadeca-3,13-diene (M(4p)) have been studied by ESI
      mass spectrometry as the model analytes. We have shown that these two molecules
      are not representatively transferred from solution to gas phase by ESI; rather,
      they undergo fragmentation inside the charged droplets. The results indicated
      that a charged analyte such as 1 was possibly unstable inside the neutral core of
      the ES droplet and undergoes fragmentation due to the Coulombic repulsion
      imparted by the surface protons. Brownian motion of the neutral analyte such as
      M(4p) inside the droplet, on the other hand, may lead to proton attachment on
      interaction with the charged surface causing destabilization that leads to
      fragmentation of M(4p) and release of resonance stabilized allyl cations from the
      core of the droplet. Detailed solvent dependence and collision-induced
      dissociation (CID) studies provided compelling evidences that the fragmentation
      of the analytes indeed occurs inside the charged ES droplets. A viable model of
      molecular transformations inside the ES droplet was proposed based on these
      results to rationalize the behavior of the analyte molecules inside the charged
      ES droplets.

PMID- 21952885
TI  - Topography and field effects in secondary ion mass spectrometry--part I:
      conducting samples.
AB  - Quantitative chemical characterization of surfaces with topography by secondary
      ion mass spectrometry (SIMS) remains a significant challenge due to the lack of
      systematic and validated measurement methods. In this study, we combine an
      experimental approach using a simple model system with computer simulation using
      SIMION, to understand and quantify the key factors that give rise to unwanted
      topographic artefacts in SIMS images of conducting samples with microscale
      topography. Experimental data are acquired for gold wires (diameters 33 to 125
      MUm) mounted onto silicon wafers. Significant loss of ion intensities and
      shadowing arise from the distortion of the extraction field, and the chemical
      analysis over the whole of the sample surface is difficult. For large primary ion
      incidence angles of >=55 degrees  to the surface normal, a fraction of the
      primary ions are scattered from the target and impact the substrate, emitting
      secondary ions that may be mistaken as originating from the wire. For conducting
      samples, topographic field effects may be reduced by the use of a smaller
      extraction voltage and an extraction delay. The effects of an extraction delay on
      ion intensities, mass resolution and time-of-flight are studied, and its
      application is demonstrated on an anisotropically etched silicon sample. The use
      of a simple sample holder with a V-shaped groove to reduce topographic field
      effects for wires is also presented. Using these results, we provide clear
      guidance to analysts for the diagnosis and identification of topography effects
      in SIMS, and present key recommendations to minimize them in practical analysis.

PMID- 21952886
TI  - Identification of different copper green pigments in Renaissance paintings by
      cluster-TOF-SIMS imaging analysis.
AB  - Time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging using cluster
      primary ion beams is used for the identification of a green painting layer on the
      scene The Angels Concert from the Issenheim Altarpiece (painted in 1516) from a
      German Renaissance painter, Matthias Grunewald. Copper carboxylate clusters
      inside a basic copper chloride (atacamite) layer have been identified and located
      in the copper green layer. The mechanisms of transformation of atacamite into
      copper carboxylates may be initiated by an aging of the paint layers. The
      combination of the high mass resolution of the technique together with a
      micrometer spatial resolution and the possibility to simultaneously identify both
      minerals and organics, has proven to be the method of choice for the study of the
      stratigraphy of a paint cross-section.

PMID- 21952887
TI  - Liquid microjunction surface sampling probe fluid dynamics: characterization and
      application of an analyte plug formation operational mode.
AB  - The recently discovered sample plug formation and injection operational mode of a
      continuous flow, coaxial tube geometry, liquid microjunction surface sampling
      probe (LMJ-SSP) was further characterized and applied for concentration and
      mixing of analyte extracted from multiple areas on a surface and for nanoliter
      scale chemical reactions of sampled material. A transparent LMJ-SSP was
      constructed and colored analytes were used so that the surface sampling process,
      plug formation, and the chemical reactions could be visually monitored at the
      sampling end of the probe before being analyzed by mass spectrometry of the
      injected sample plug. Injection plug peak widths were consistent for plug hold
      times as long as the 8 min maximum attempted (RSD below 1.5%). Furthermore,
      integrated injection peak signals were not significantly different for the range
      of hold times investigated. The ability to extract and completely mix individual
      samples within a fixed volume at the sampling end of the probe was demonstrated
      and a linear mass spectral response to the number of equivalent analyte spots
      sampled was observed. Using the color and mass changing chemical reduction of the
      redox dye 2,6-dichlorophenol-indophenol with ascorbic acid, the ability to
      sample, concentrate, and efficiently run reactions within the same plug volume
      within the probe was demonstrated.

PMID- 21952888
TI  - Tandem mass spectrometric analysis of a mixture of isobars using the survival
      yield technique.
AB  - Collision induced dissociation tandem mass spectrometry experiments were
      performed to unequivocally separate compounds from an isobaric mixture of two
      products. The Survival Yield curve was obtained and is shown to consist in a
      linear combination of the curves corresponding to the two components separately.
      For such a mixture, a plateau appears on the diagram in lieu of the continuous
      decrease expected allowing for the structural study of the two components
      separately. The width of the plateau critically relates to the fragmentation
      parameters of the two molecular ions, which need to be sufficiently different
      structurally for the plateau to be observed. However, at constant fragmentation
      parameters, we have observed the width significantly increases at large m/z. This
      makes the separation more and more efficient as isobars have larger m/z and the
      technique complementary to those applicable at low m/z only. We have observed
      that the vertical position of the plateau relates linearly to the relative
      concentration of the two compounds that may be useful for quantification.
      Repeatability was estimated at 2% on a quadrupole ion trap. An advantage of using
      survival yield curves only, is that a priori knowledge of the respective
      fragmentation patterns of the two isobars becomes unnecessary. Consequently,
      similar performances are obtained if fragments are isobaric, which is also
      demonstrated in our study. The critical case of reverse peptides, at low m/z and
      similar fragmentation parameters, is also presented as a limitation of the
      method.

PMID- 21952889
TI  - Identification of proteins and phosphoproteins using pulsed Q collision induced
      dissociation (PQD).
AB  - Pulsed Q collision induced dissociation (PQD) was developed to facilitate
      detection of low-mass reporter ions from labeling reagents (e.g., iTRAlphaQ) in
      peptide quantification using an LTQ mass spectrometer (MS). Despite the large
      number of linear ion traps worldwide, the use and optimization of PQD for protein
      identification have been limited, in part due to less effective ion fragmentation
      relative to the collision induced dissociation (CID). PQD expands the m/z
      coverage of fragment ions to the lower m/z range by circumventing the typical low
      mass cut-off of an ion trap MS. Since database searching relies on the matching
      between theoretical and observed spectra, it is not clear how ion intensity and
      peak number might affect the outcomes of a database search. In this report, we
      systematically evaluated the attributes of PQD mass spectra, performed intensity
      optimization, and assessed the benefits of using PQD on the identification of
      peptides and phosphopeptides from an LTQ. Based on head-to-head comparisons
      between CID (higher intensity) and PQD (better m/z coverage), peptides identified
      using PQD generally have Xcorr scores lower than those using CID. Such score
      differences were considerably diminished by the use of 0.1% m-nitrobenzyl alcohol
      (m-NBA) in mobile phases. The ion intensities of both CID and PQD were adversely
      affected by increasing m/z of the precursor, with PQD more sensitive than CID. In
      addition to negating the 1/3 rule, PQD enhances direct bond cleavage and
      generates patterns of fragment ions different from those of CID, particularly for
      peptides with a labile functional group (e.g., phosphopeptides). The higher
      energy fragmentation pathway of PQD on peptide fragmentation was further compared
      to those of CID and the quadrupole-type activation in parallel experiments.

PMID- 21952890
TI  - Heme binding in gas-phase holo-myoglobin cations: distal becomes proximal?
AB  - His64 and His93 are the two well-known sites of heme binding in water-dissolved
      holo-myoglobin, with His93 being a proximal, strongly binding partner, while the
      distal His64 weakly coordinates to the heme through a small-molecule ligand,
      e.g., water or O(2). The heme bonding scheme in a water-free environment is as
      yet unclear. Here we employed electron transfer dissociation tandem mass
      spectrometry to study the preferential attachment site of the ferri-heme (Fe(3+))
      in electrospray-produced 12+, 14+, and 16+ holo-myoglobin ions. Contrary to
      expectations, in lower-charge complexes that should have a structure resembling
      that in solution, the heme seems to be preferentially attached to the "distal"
      histidine. In contrast, in the highest studied charge state, the "proximal"
      histidine is the site of preferential attachment; the 14+ charge state is an
      intermediate case. This surprising finding raises a question of heme coordination
      in proteins transferred to water-free environment, as well as the effect of the
      protonation sites on heme bonding.

PMID- 21952891
TI  - Tandem mass spectrometric characterization of thiol peptides modified by the
      chemoselective cationic sulfhydryl reagent (4-iodobutyl)triphenylphosphonium-
      effects of a cationic thiol derivatization on peptide fragmentation.
AB  - Fixed charge chemical modifications on peptides and proteins can impact
      fragmentation behaviors in tandem mass spectrometry (MS/MS). In this study, we
      employed a thiol-specific cationic alkylation reagent, (4
      iodobutyl)triphenylphosphonium (IBTP), to selectively modify cysteine thiol
      groups in mitochondrial proteome samples. Tandem mass spectrometric
      characteristics of butyltriphenylphosphonium (BTP)-modified peptides were
      evaluated by comparison to their carbamidomethylated (CAM) analogues using a
      quadrupole time-of-flight (Q-TOF) instrument under low energy collision-induced
      dissociation (CID) conditions. Introduction of the fixed charge modification
      resulted in the observation of peptide and fragment (b(n) and y(n)) ions with
      higher charge states than those observed for CAM-modified analogues. The charged
      BTP moiety had a significant effect on the neighboring amide bond fragmentation
      products. A decrease in relative abundances of the product ions at the
      corresponding cleavage sites was observed compared with those from the CAM
      modified derivatives. This effect was particularly noticeable when an Xxx-Pro
      bond was in the vicinity of a BTP group. We hypothesized that the presence of a
      phosphonium moiety will reduce the tendency for protonation of the proximal amide
      bonds in the peptide backbone. Indeed, calculations indicated that proton
      affinities of backbone amide bonds close to the modified cysteine residues were
      generally 20-50 kcal/mol lower for BTP-modified peptides than for the unmodified
      or CAM-modified analogues with the sequence motif -Ala-Cys-Ala(n)-Ala(2)-, -Ala
      Cys-Ala(n)-Pro-Ala-, and -Ala-Pro-Ala(n)-Cys-Ala-, n=0-3.

PMID- 21952892
TI  - ETD in a traveling wave ion guide at tuned Z-spray ion source conditions allows
      for site-specific hydrogen/deuterium exchange measurements.
AB  - The recent application of electron transfer dissociation (ETD) to measure the
      hydrogen exchange of proteins in solution at single-residue resolution (HX-ETD)
      paves the way for mass spectrometry-based analyses of biomolecular structure at
      an unprecedented level of detail. The approach requires that activation of
      polypeptide ions prior to ETD is minimal so as to prevent undesirable gas-phase
      randomization of the deuterium label from solution (i.e., hydrogen scrambling).
      Here we explore the use of ETD in a traveling wave ion guide of a quadrupole-time
      of-flight (Q-TOF) mass spectrometer with a "Z-spray" type ion source, to measure
      the deuterium content of individual residues in peptides. We systematically
      identify key parameters of the Z-spray ion source that contribute to collisional
      activation and define conditions that allow ETD experiments to be performed in
      the traveling wave ion guide without gas-phase hydrogen scrambling. We show that
      ETD and supplemental collisional activation in a subsequent traveling wave ion
      guide allows for improved extraction of residue-specific deuterium contents in
      peptides with low charge. Our results demonstrate the feasibility, and illustrate
      the advantages of performing HX-ETD experiments on a high-resolution Q-TOF
      instrument equipped with traveling wave ion guides. Determination of parameters
      of the Z-spray ion source that contribute to ion heating are similarly pertinent
      to a growing number of MS applications that also rely on an energetically gentle
      transfer of ions into the gas-phase, such as the analysis of biomolecular
      structure by native mass spectrometry in combination with gas-phase ion-ion/ion
      neutral reactions or ion mobility spectrometry.

PMID- 21952893
TI  - Structure and reactivity of the N-acetyl-cysteine radical cation and anion: does
      radical migration occur?
AB  - The structure and reactivity of the N-acetyl-cysteine radical cation and anion
      were studied using ion-molecule reactions, infrared multi-photon dissociation
      (IRMPD) spectroscopy, and density functional theory (DFT) calculations. The
      radical cation was generated by first nitrosylating the thiol of N-acetyl
      cysteine followed by the homolytic cleavage of the S-NO bond in the gas phase.
      IRMPD spectroscopy coupled with DFT calculations revealed that for the radical
      cation the radical migrates from its initial position on the sulfur atom to the
      alpha-carbon position, which is 2.5 kJ mol(-1) lower in energy. The radical
      migration was confirmed by time-resolved ion-molecule reactions. These results
      are in contrast with our previous study on cysteine methyl ester radical cation
      (Osburn et al., Chem. Eur. J. 2011, 17, 873-879) and the study by Sinha et al.
      for cysteine radical cation (Phys. Chem. Chem. Phys. 2010, 12, 9794-9800) where
      the radical was found to stay on the sulfur atom as formed. A similar approach
      allowed us to form a hydrogen-deficient radical anion of N-acetyl-cysteine, (M -
      2H)( *- ). IRMPD studies and ion-molecule reactions performed on the radical
      anion showed that the radical remains on the sulfur, which is the initial and
      more stable (by 63.6 kJ mol(-1)) position, and does not rearrange.

PMID- 21952894
TI  - Structural characterization of oxidized glycerophosphatidylserine: evidence of
      polar head oxidation.
AB  - Non-oxidized phosphatidylserine (PS) is known to play a key role in apoptosis but
      there is considerable research evidence suggesting that oxidized PS also plays a
      role in this event, leading to the increasing interest in studying PS oxidative
      modifications. In this work, different PS (1-palmitoyl-2-linoleoyl-sn-glycero-3
      phospho-L-serine (PLPS), 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine
      (POPS), and 1,2-dipalmitoyl-sn-glycero-3-phospho-L-serine (DPPS) were oxidized in
      vitro by hydroxyl radical, generated under Fenton reaction conditions, and the
      reactions were monitored by ESI-MS in negative mode. Oxidation products were then
      fractionated by thin layer chromatography (TLC) and characterized by tandem mass
      spectrometry (MS/MS). This approach allowed the identification of hydroxyl,
      peroxy, and keto derivatives due to oxidation of unsaturated fatty acyl chains.
      Oxidation products due to oxidation of serine polar head were also identified.
      These products, with lower molecular weight than the non-modified PS, were
      identified as [M - 29 - H](-) (terminal acetic acid), [M - 30 - H](-) (terminal
      acetamide), [M - 13 - H](-) (terminal hydroperoxyacetaldehyde), and [M - 13 - H](
      ) (terminal hydroxyacetaldehyde plus hydroxy fatty acyl chain). Phosphatidic acid
      was also formed in these conditions. These findings confirm the oxidation of the
      serine polar head induced by the hydroxyl radical. The identification of these
      modifications may be a valuable tool to evaluate phosphatidylserine alteration
      under physiopathologic conditions and also to help understand the biological role
      of phosphatidylserine oxidation in the apoptotic process and other biological
      functions.

PMID- 21952895
TI  - Electrospray ionization mass spectrometry of palladium(II)
      quinolinylaminophosphonate complexes.
AB  - The mass spectrometric behavior of palladium(II) halide complexes of three types
      of quinolinylaminophosphonates, diethyl and dibutyl esters of [alpha-anilino
      (quinolin-2-yl)methyl]phosphonic (L1, L2), [alpha-anilino-(quinolin-3
      yl)methyl]phosphonic (L3, L4), and [alpha-(quinolin-3-ylamino)-N
      benzyl]phosphonic acid (L5, L6), was investigated under positive ion electrospray
      ionization conditions. Each type of ligand forms complexes with different metal
      ligand interactions. Mononuclear dihalide adducts cis-[Pd(L1/L2)X(2)] (1-4) and
      trans-[Pd(L3/L4)(2)X(2)] (5-8) as well as dinuclear tetrahalide complexes
      [Pd(2)(L5/L6)(3)X(4)] (9-12) (X=Cl, Br) are formed by metal bonding either
      through the quinoline or both the quinoline and amino nitrogen atoms. The
      sodiated molecule [M + Na](+) is observed in the mass spectra of all the
      complexes, and its abundance as well as the fragmentation pathway depend on the
      type of the complex. In the cis complexes (1-4) the initial decomposition goes
      under two fragmentation routes: those in which the sodium molecular adduct
      sequentially loses halides HX/NaX and those in which this loss is in the
      competition with the loss of dialkyl phosphite. The predominant pathways for
      decomposition of trans dihalide (5-8) and tetrahalide (9-12) complexes include
      three competitive reactions; the loss of halides, dialkyl phosphites and the
      intact phosphonate ligand molecule and its fragments formed by ester dissociation
      or complete loss of the phosphonate ester moiety. A series of acetonitrile
      adducts and cluster ions derived from dimolecular clusters [2M + Na](+) were also
      detected. The most important fragmentation patterns are rationalized and
      supported by the MS(n) studies.

PMID- 21952896
TI  - Optimization and comparison of ESI and APCI LC-MS/MS methods: a case study of
      Irgarol 1051, Diuron, and their degradation products in environmental samples.
AB  - A systematic and detailed optimization strategy for the development of
      atmospheric pressure ionization (API) LC-MS/MS methods for the determination of
      Irgarol 1051, Diuron, and their degradation products (M1, DCPMU, DCPU, and DCA)
      in water, sediment, and mussel is described. Experimental design was applied for
      the optimization of the ion sources parameters. Comparison of ESI and APCI was
      performed in positive- and negative-ion mode, and the effect of the mobile phase
      on ionization was studied for both techniques. Special attention was drawn to the
      ionization of DCA, which presents particular difficulty in API techniques.
      Satisfactory ionization of this small molecule is achieved only with ESI positive
      ion mode using acetonitrile in the mobile phase; the instrumental detection limit
      is 0.11 ng/mL. Signal suppression was qualitatively estimated by using purified
      and non-purified samples. The sample preparation for sediments and mussels is
      direct and simple, comprising only solvent extraction. Mean recoveries ranged
      from 71% to 110%, and the corresponding (%) RSDs ranged between 4.1 and 14%. The
      method limits of detection ranged between 0.6 and 3.5 ng/g for sediment and
      mussel and from 1.3 to 1.8 ng/L for sea water. The method was applied to sea
      water, marine sediment, and mussels, which were obtained from marinas in Attiki,
      Greece. Ion ratio confirmation was used for the identification of the compounds.

PMID- 21952897
TI  - Gas chromatographic-ion trap mass spectrometric analysis of volatile organic
      compounds by ion-molecule reactions using the electron-deficient reagent ion
      CCl3(+).
AB  - When using tetrachloromethane as the reagent gas in gas chromatography-ion trap
      mass spectrometry equipped with hybrid ionization source, the cation CCl(3)(+)
      was generated in high abundance and further gas-phase experiments showed that
      such an electron-deficient reagent ion CCl(3)(+) could undergo interesting ion
      molecule reactions with various volatile organic compounds, which not only
      present some informative gas-phase reactions, but also facilitate qualitative
      analysis of diverse volatile compounds by providing unique mass spectral data
      that are characteristic of particular chemical structures. The ion-molecule
      reactions of the reagent ion CCl(3)(+) with different types of compounds were
      studied, and results showed that such reactions could give rise to structurally
      diagnostic ions, such as [M+CCl(3) - HCl](+) for aromatic hydrocarbons, [M -
      OH](+) for saturated cyclic ether, ketone, and alcoholic compounds, [M - H](+)
      ion for monoterpenes, M(.+) for sesquiterpenes, [M - CH(3)CO](+) for esters, as
      well as the further fragment ions. The mechanisms of ion-molecule reactions of
      aromatic hydrocarbons, aliphatic ketones and alcoholic compounds with the reagent
      ion CCl(3)(+) were investigated and proposed according to the information
      provided by MS/MS experiments and theoretical calculations. Then, this method was
      applied to study volatile organic compounds in Dendranthema indicum var.
      aromaticum and 20 compounds, including monoterpenes and their oxygen-containing
      derivatives, aromatic hydrocarbon and sesquiterpenes were identified using such
      ion-molecule reactions. This study offers a perspective and an alternative tool
      for the analysis and identification of various volatile compounds.

PMID- 21952898
TI  - Comprehensive two-dimensional separation of hydroxylated polybrominated diphenyl
      ethers by ultra-performance liquid chromatography coupled with ion mobility-mass
      spectrometry.
AB  - A comprehensive two-dimensional system coupling ultra-performance liquid
      chromatography (UPLC) and ion mobility-mass spectrometry (IM-MS) has been applied
      for the separation and analysis of hydroxylated polybrominated diphenyl ethers
      (OH-PBDEs). A complex mixture containing 23 OH-PBDE congeners ranging from
      hydroxylated monobromodiphenyl ether (OH-monoBDE) to hydroxylated
      octabromodiphenyl ether (OH-octaBDE) was satisfactorily separated within 16 min
      of analysis time. The first-dimensional reversed-phase UPLC was performed on a
      sub-2 MUm BEH C(18) chromatographic column using acetonitrile-water gradient
      elution program with a flow rate ramp. It enabled excellent chromatographic
      separation for both between-class and within-class OH-PBDEs based on their
      differences in hydrophobicity. Following the pre-ionization resolution in the
      first dimension, the second-dimensional IM-MS employed a hybrid electrospray
      quadrupole ion mobility time-of-flight mass spectrometer and added an extra post
      ionization separation for between-class OH-PBDE congeners on account of their
      relative mobility disparity during a very short period of 8.80 ms. The
      orthogonality of the developed two-dimensional system was evaluated with the
      correlation coefficient of 0.9665 and peak spreading angle of 14.87 degrees . The
      peak capacity of the system was calculated to be approximately 2 and 15 times
      higher than that of the two dimensions used alone, respectively. The two
      dimensional separation plane also contributed to the removal of background
      interference ions and the enhanced confidence in the characterization of OH-PBDEs
      of interest.

PMID- 21952899
TI  - Infrared multiple photon dissociation action spectroscopy and theoretical studies
      of triethyl phosphate complexes: effects of protonation and sodium cationization
      on structure.
AB  - The gas-phase structures of protonated and sodium cationized complexes of
      triethyl phosphate, [TEP + H](+) and [TEP + Na](+), are examined via infrared
      multiple photon dissociation (IRMPD) action spectroscopy using tunable IR
      radiation generated by a free electron laser, a Fourier transform ion cyclotron
      resonance mass spectrometer with an electrospray ionization source, and
      theoretical electronic structure calculations. Measured IRMPD action spectra are
      compared to linear IR spectra calculated at the B3LYP/6-31 G(d,p) level of theory
      to identify the structures accessed in the experimental studies. For comparison,
      theoretical studies of neutral TEP are also performed. Sodium cationization and
      protonation produce changes in the central phosphate geometry, including an
      increase in the alkoxy ?OPO bond angle and shortening of the alkoxy P-O bond.
      Changes associated with protonation are more pronounced than those produced by
      sodium cationization.

PMID- 21952900
TI  - IonCCD detector for miniature sector-field mass spectrometer: investigation of
      peak shape and detector surface artifacts induced by keV ion detection.
AB  - A recently described ion charge coupled device detector IonCCD (Sinha and
      Wadsworth, Rev. Sci. Instrum. 76(2), 2005; Hadjar, J. Am. Soc. Mass Spectrom.
      22(4), 612-624, 2011) is implemented in a miniature mass spectrometer of sector
      field instrument type and Mattauch-Herzog (MH)-geometry (Rev. Sci. Instrum.
      62(11), 2618-2620, 1991; Burgoyne, Hieftje and Hites J. Am. Soc. Mass Spectrom.
      8(4), 307-318, 1997; Nishiguchi, Eur. J. Mass Spectrom. 14(1), 7-15, 2008) for
      simultaneous ion detection. In this article, we present first experimental
      evidence for the signature of energy loss the detected ion experiences in the
      detector material. The two energy loss processes involved at keV ion kinetic
      energies are electronic and nuclear stopping. Nuclear stopping is related to
      surface modification and thus damage of the IonCCD detector material. By
      application of the surface characterization techniques atomic force microscopy
      (AFM) and X-ray photoelectrons spectroscopy (XPS), we could show that the
      detector performance remains unaffected by ion impact for the parameter range
      observed in this study. Secondary electron emission from the (detector) surface
      is a feature typically related to electronic stopping. We show experimentally
      that the properties of the MH-mass spectrometer used in the experiments, in
      combination with the IonCCD, are ideally suited for observation of these stopping
      related secondary electrons, which manifest in reproducible artifacts in the mass
      spectra. The magnitude of the artifacts is found to increase linearly as a
      function of detected ion velocity. The experimental findings are in agreement
      with detailed modeling of the ion trajectories in the mass spectrometer. By
      comparison of experiment and simulation, we show that a detector bias retarding
      the ions or an increase of the B-field of the IonCCD can efficiently suppress the
      artifact, which is necessary for quantitative mass spectrometry.

PMID- 21952901
TI  - An alternative paper based tissue washing method for mass spectrometry imaging:
      localized washing and fragile tissue analysis.
AB  - Surface treatment of biological tissue sections improves detection of peptides
      and proteins for mass spectrometry imaging. However, liquid surface treatments
      can result in diffusion of surface analytes and fragile tissue sections can be
      easily damaged by typical washing solvents. Here, we present a new surface
      washing procedure for mass spectrometry imaging. This procedure uses solvent
      wetted fiber-free paper to enable local washing of tissue sections for mass
      spectrometry imaging and tissue profiling experiments. In addition, the method
      allows fragile tissues that cannot be treated by conventional washing techniques
      to be analyzed by mass spectrometry imaging.

PMID- 21952903
TI  - The laryngoscope gets a new editor.

PMID- 21952904
TI  - Does balloon catheter sinuplasty have a role in the surgical management of
      pediatric sinus disease?

PMID- 21952905
TI  - Anesthetic complications in pediatric patients undergoing cochlear implantation.
AB  - OBJECTIVES/HYPOTHESIS: Cochlear implantation (CI) is effective in the treatment
      of childhood sensorineural hearing loss and is associated with minimal surgical
      complications. We investigated the incidence of anesthetic complications in young
      patients undergoing general anesthesia for CI. STUDY DESIGN: Retrospective chart
      review. METHODS: A retrospective chart review of 123 patients younger than 18
      years, who underwent CI between 2007 and 2008, was conducted for identification
      of intra- and postoperative anesthesia-related complications. The relation of
      collected variable to the complication events was analyzed using logistic
      regression. RESULTS: Of the 123 CI procedures, eight patients had nine anesthesia
      related complications, yielding a complication rate of 6.5% and included the
      following: postoperative wheezing/stridor (5 cases), laryngospasm (3 cases), and
      emesis during inhalational induction (1 case). Divided by age group, 12 patients
      were <12 months with one complication (8%), 18 patients were between 1 and 2
      years with one complication (5.6%), 35 patients were between 2 and 5 years with
      one complication (3%), 39 patients were between 5 and 12 years with five
      complications (13%), and 19 patients were older than 12 years with no
      complication (0%). Logistic regression failed to identify a significant
      association of any collected variable(s) with the observed complications. The
      incidence of complications is similar to that previously reported in elderly
      patients (4.3%) (Pearson chi(2) , P = .523). CONCLUSIONS: General anesthesia is
      well tolerated by pediatric patients undergoing CI, even under 1 year of age.
      Significant perioperative complications are primarily respiratory, are usually
      free of long-term sequelae, and occur with an incidence similar to other reported
      age groups.

PMID- 21952907
TI  - Predictors of survival among older adults with ependymoma.
AB  - The biological process of aging encompasses a multitude of complex physiological
      and lifestyle changes that may alter the way typical prognostic factors affect
      survival among older ependymoma patients. Because very little is known about the
      clinical significance of traditional prognostic factors and the magnitude of
      their effects among older individuals, the purpose of this study was to evaluate
      the associations between survival and demographic and tumor characteristics among
      patients with ependymoma who were 60 years of age or older. Using the 1973-2007
      dataset from the Surveillance, Epidemiology and End Results (SEER) program, we
      evaluated the impact of several factors on both overall and ependymoma-specific
      survival, utilizing multivariable Cox proportional hazards regression. We
      identified 367 ependymoma cases who were 60 years of age or older at diagnosis
      and had complete data from SEER. Of these, 19 (5.2%) had anaplastic tumors; all
      others were low-grade tumors. Age, tumor site, extent of surgery, and tumor
      histology were found to be significant predictors of ependymoma prognosis. The
      strongest predictor of poor outcome was supratentorial tumor location (adjusted
      HR: 6.94, 95% CI: 3.19-15.08, compared to spinal cord tumors). Our study suggests
      that tumor location, tumor histology, and surgical margin may be key predictors
      of survival among older ependymoma patients. We believe our study is one of the
      first to assess the prognostic value of these factors for ependymoma survival
      exclusively in an older patient population.

PMID- 21952906
TI  - Factors associated with physical activity among Canadian high school students.
AB  - OBJECTIVES: Identifying multi-level factors affecting physical activity (PA)
      levels among adolescents is essential to increasing activity to promote health
      within this population. This study examines the associations between PA and 11
      independent factors among Manitoba high school students. METHODS: The sample
      included 31,202 grade 9-12 students who completed the Manitoba Youth Health
      Survey. Associations between PA and independent factors were examined separately
      and through multivariate regression. Analyses were stratified by gender. RESULTS:
      Perception of athletic ability, school location, parental encouragement and
      number of active friends were strong predictors of activity for moderately active
      and active males and females. Grade was a significant predictor of PA for females
      at both levels of activity but only significant for males when comparing active
      to inactive students. Perception of schoolwork and means of transport were
      minimally associated with PA. CONCLUSIONS: Results highlight the importance of
      targeting multiple levels of influence to increase PA among youth. Programs
      should focus on older students, females and those who are inactive or moderately
      active. In addition, social modeling of PA and increasing self-efficacy around
      activity should be encouraged.

PMID- 21952908
TI  - Bortezomib-induced congestive cardiac failure in a patient with multiple myeloma.
AB  - Bortezomib therapy is known to be associated with neurological side effects and
      thrombocytopenia. Its cardiac side effects are however not well known. The
      patient, a 70-year-old woman, with a previous history of myocardial infarction
      and subsequent coronary stenting, was detected to have multiple myeloma stage
      IIIa. She was started on Inj. Bortezomib (1.3 mg/m(2)) and Tab. Dexamethasone 40
      mg on a weekly basis. She showed good response to therapy. Three days after
      administration of the 22nd dose of bortezomib, she presented to the hospital with
      congestive cardiac failure. Echocardiography revealed a drop in the left
      ventricular ejection fraction from pretreatment levels of 45-50 to 25%. Patient
      was treated medically for left ventricular failure secondary to a suspected
      ischemic etiology. Coronary angiography revealed non-critical coronary artery
      disease with patent right coronary artery and left circumflex stents. The N
      terminal pro-brain natriuretic peptide (NT-proBNP) levels that were initially
      raised 4,030 pg/ml (<125 pg/ml) declined to 2,280 pg/ml a week later and
      subsequently normalized over the next 2 weeks. The patient responded well to
      treatment and was then discharged. The left ventricular ejection normalized over
      the next 3 months. Cardiac side effects of bortezomib are not well reported.
      Elderly patients and those with preexisting cardiac conditions could be at
      increased cardiovascular risk. Since this risk increases once a cumulative dose
      of 20 mg/m(2) has been administered, patients need to be monitored more
      intensively once this threshold has been attained. Increased awareness of these
      cardiac side effects is necessary for patients' safety.

PMID- 21952909
TI  - Enantioselective organocatalytic asymmetric allylic alkylation.
      Bis(phenylsulfonyl)methane addition to MBH carbonates.
AB  - The highly enantioselective asymmetric allylic alkylation of Morita-Baylis
      Hillman carbonates with bis(phenylsulfonyl)methane is presented. The reaction is
      simply catalyzed by cinchona alkaloid derivatives affording the final alkylated
      products in good yields and enantioselectivities.

PMID- 21952910
TI  - Rhinocerebral mucormycosis--a case report.
AB  - BACKGROUND: Rhinocerebral mucormycosis (RCM) is a rare, fulminating opportunistic
      fungal infection caused by a fungus of order Mucorales. These fungi are
      ubiquitus, subsisting on decaying vegetation and diverse organic material.
      Although fungi and spores of Mucorales show minimal intrinsic pathogenicity
      towards normal person, they can initiate aggressive and fulminating infection in
      immunocompromised host. Since RCM occurs infrequently, it may pose a diagnostic
      and therapeutic dilemma for those who are not familiar with its clinical
      presentation. CASE REPORT: We present a patient with classical presentation of
      RCM involving paranasal sinuses, orbit, and cranial base who was treated by
      combination of aggressive surgical and medical therapy. DISCUSSION: The purpose
      of this paper is to draw attention to the clinical presentation and pathogenesis
      of RCM and to emphasize need for high index of suspicion in diagnosis and
      treatment.

PMID- 21952911
TI  - Reply to the letter by Zhang and Hoffman: Comments on corneal intrastromal tissue
      modeling with the femtosecond laser.

PMID- 21952912
TI  - "Kilroy was here"-- plus!

PMID- 21952914
TI  - Synthesis of encephalomyocarditis virus in a cell-free system: from DNA to RNA
      virus in one tube.
AB  - Virus particles are used in vaccination, drug delivery, and material sciences.
      Here we devised a system where the RNA virus encephalomyocarditis virus (EMCV) is
      synthesized from DNA templates in vitro. When a plasmid or a PCR product
      harboring the full-length cDNA of EMCV in the T7 promoter/terminator unit was
      incubated in a HeLa cell extract supplemented with T7 RNA polymerase, EMCV was
      produced within 4 h at an efficiency of over 10-fold compared with the system
      programmed with the EMCV RNA. The EMCV RNA transcribed by the virally encoded RNA
      dependent RNA polymerase was predominantly incorporated into the EMCV particle
      even in the presence of a larger amount of the EMCV RNA transcribed by T7 RNA
      polymerase from the plasmid.

PMID- 21952915
TI  - Hydrogen abstraction reactions of OH radicals with CH3CH2CH2Cl and CH3CHClCH3: a
      mechanistic and kinetic study.
AB  - The hydrogen abstraction reactions of OH radicals with CH3CH2CH2Cl and CH3CHClCH3
      (R2) have been investigated theoretically by a dual-level direct dynamics method.
      The optimized geometries and frequencies of the stationary points are calculated
      at the B3LYP/6-311G(d,p) level. To improve the reaction enthalpy and potential
      barrier of each reaction channel, the single point energy calculation is
      performed by the BMC-CCSD method. Using canonical variational transition-state
      theory (CVT) with the small-curvature tunneling correction, the rate constants
      are evaluated over a wide temperature range of 200-2000 K at the BMC
      CCSD//B3LYP/6-311G(d,p) level. For the reaction channels with the negative
      barrier heights, the rate constants are calculated by using the CVT. The
      calculated total rate constants are consistent with available experimental data.
      The results show that at lower temperatures, the tunneling correction has an
      important contribution in the calculation of rate constants for all the reaction
      channels with the positive barrier heights, while the variational effect is found
      negligible for some reaction channels. For reactions OH radicals with CH3CH2CH2Cl
      (R1) and CH3CHClCH3 (R2), the channels of H-abstraction from -CH2 - and -CHCl
      groups are the major reaction channels, respectively, at lower temperatures. With
      temperature increasing, contributions from other channels should be taken into
      account. Finally, the total rate constants are fitted by two models, i.e., three
      parameter and four-parameter expressions. The enthalpies of formation of the
      species CH3CHClCH2, CH3CHCH2Cl, and CH3CH2CH2Cl are evaluated by isodesmic
      reactions.

PMID- 21952916
TI  - Enzyme replacement therapy induces T-cell responses in late-onset Pompe disease.
AB  - INTRODUCTION: Enzyme replacement therapy (ERT) in ultra-orphan Pompe disease
      generates anti-rhGAA antibodies, which may interfere with efficacy. METHODS:
      rhGAA-specific T-cell responses were examined at different time-points in 6
      Hungarian patients treated with rhGAA and compared with 1 untreated patient and 5
      healthy controls. RESULTS: The ex vivo percentage of activated T cells was
      increased in treated patients. rhGAA stimulation in vitro generated a dose
      dependent increase in intracellular interferon-gamma (IFN-gamma) expression in
      CD4(+) and CD8(+) T cells. Isolated CD4(+) and CD8(+) T cells produced increased
      amounts of IFN-gamma and tumor necrosis factor-alpha (TNF-alpha) in half of the
      patients after in vitro stimulation with rhGAA, whereas interleukin (IL)-4, IL-6,
      and IL-17 levels were not elevated. Expression of cytotoxic FasL and perforin
      molecules by natural killer (NK), NKT-like, and CD8(+) T cells were not increased
      ex vivo. CONCLUSIONS: We found that enzyme replacement therapy (ERT) induces pro
      inflammatory T-cell responses in addition to the antibody response in Pompe
      disease.

PMID- 21952917
TI  - Controllable formation and TEM spatial visualization of cross-linked gold
      nanoparticle spherical aggregates.
AB  - Gold nanoparticles (NPs) were assembled and cross-linked into spherical
      aggregates by colloidal emulsion evaporation and ligand exchanging. The optical
      absorption, conventional transmission electron microscopy (TEM) and bright field
      (BF) TEM tomography confirm that the cross-linking of the pre-condensed
      aggregates generates high stability and compactness.

PMID- 21952919
TI  - Rocaglamide and a XIAP inhibitor cooperatively sensitize TRAIL-mediated apoptosis
      in Hodgkin's lymphomas.
AB  - Although most of the patients with Hodgkin's lymphoma (HL) can be cured by the
      current regimen of high-dose multiagent chemotherapy, the treatment causes high
      risks of later toxicities including secondary malignancies. Therefore, new
      rational strategies are needed for HL treatment. Tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL) is a promising anticancer agent due to its
      tumor selectivity and its lack of toxicity for normal cells. Unfortunately, many
      cancers remain resistant to TRAIL including HL. HL is characterized by enhanced
      expression of cellular caspase-8 (FLICE)-inhibitory protein (c-FLIP) and X-linked
      inhibitor of apoptosis (XIAP), which block receptor-mediated apoptosis by
      inhibiting caspase-8 and caspase-3, respectively. We have recently discovered the
      herbal compound Rocaglamide, which breaks TRAIL-resistance in acute T cell
      leukemia through inhibition of c-FLIP expression. We have also shown that small
      molecule XIAP inhibitors can sensitize TRAIL-mediated apoptosis in several
      resistant tumors. However, whether targeting XIAP or c-FLIP is also a suitable
      strategy to prime HL cells for TRAIL-induced apoptosis has not yet been
      investigated. In our study, we show that Rocaglamide suppresses c-FLIP expression
      in HL cells in a dose- and time-dependent manner. However, downregulation of c
      FLIP alone was not sufficient to sensitize TRAIL-induced apoptosis in HL cells.
      Similarly, treatment of HL cells with a small molecule XIAP inhibitor resulted in
      a moderate induction of apoptosis. However, inhibition of XIAP alone was also not
      sufficient to enhance TRAIL-induced cell death. Synergistic increase in TRAIL
      mediated killing of HL cells was only obtained by combination of Rocaglamide and
      XIAP inhibitors. Our study demonstrates that targeting both c-FLIP and XIAP are
      necessary for an efficient treatment of HL.

PMID- 21952918
TI  - Evidence for gene-gene epistatic interactions among susceptibility loci for
      systemic lupus erythematosus.
AB  - OBJECTIVE: Several confirmed genetic susceptibility loci for lupus have been
      described. To date, no clear evidence for genetic epistasis in lupus has been
      established. The aim of this study was to test for gene-gene interactions in a
      number of known lupus susceptibility loci. METHODS: Eighteen single-nucleotide
      polymorphisms tagging independent and confirmed lupus susceptibility loci were
      genotyped in a set of 4,248 patients with lupus and 3,818 normal healthy control
      subjects of European descent. Epistasis was tested by a 2-step approach using
      both parametric and nonparametric methods. The false discovery rate (FDR) method
      was used to correct for multiple testing. RESULTS: We detected and confirmed gene
      gene interactions between the HLA region and CTLA4, IRF5, and ITGAM and between
      PDCD1 and IL21 in patients with lupus. The most significant interaction detected
      by parametric analysis was between rs3131379 in the HLA region and rs231775 in
      CTLA4 (interaction odds ratio 1.19, Z = 3.95, P = 7.8 * 10(-5) [FDR <=0.05], P
      for multifactor dimensionality reduction = 5.9 * 10(-45)). Importantly, our data
      suggest that in patients with lupus, the presence of the HLA lupus risk alleles
      in rs1270942 and rs3131379 increases the odds of also carrying the lupus risk
      allele in IRF5 (rs2070197) by 17% and 16%, respectively (P = 0.0028 and P =
      0.0047, respectively). CONCLUSION: We provide evidence for gene-gene epistasis in
      systemic lupus erythematosus. These findings support a role for genetic
      interaction contributing to the complexity of lupus heritability.

PMID- 21952920
TI  - Collective arousal when reuniting after temporary separation in Tonkean macaques.
AB  - Celebrations and bursts of communal joy can occur spontaneously in human
      communities based on mechanisms of emotional contagion. Some examples of similar
      collective excitement have been reported in animals when they reunite or
      anticipate rewards, but little is known about the processes and meaning of these
      multiple interactions. We experimentally studied such collective arousals in two
      captive groups of Tonkean macaques (Macaca tonkeana) within the context of
      reunions following the temporary separation of two subgroups. We compared the
      behaviors of individuals after separation periods of 2 and 48 h with a control
      period with no separation. This study showed that it is possible to reproducibly
      induce bursts of friendly interactions in which groupmates run around over a
      period of several minutes, embracing and grasping one another while displaying
      numerous affiliative vocalizations and facial expressions. The longer the period
      of separation, the higher and longer-lasting the rates of affiliative
      interactions were. Individuals affiliated more frequently with groupmates from a
      previously separated subgroup than with those having stayed in their own
      subgroup. Collective arousal was followed by a quieter period characterized by
      high rates of contact-sitting and social grooming. These results point at the
      role of collective arousals in social cohesion; they could resolve social tension
      and renew social relationships. We propose that the emotional state experienced
      by Tonkean macaques during such events represents a disposition similar to that
      giving rise to what we humans call "shared joy."

PMID- 21952921
TI  - Sinonasal surgery in Wegener's granulomatosis: is it time to go on?

PMID- 21952922
TI  - Is public communication about end-of-life care helping to inform all? Cancer news
      coverage in African American versus mainstream media.
AB  - BACKGROUND: Because cancers are a leading cause of death, these diseases receive
      a great deal of news attention. However, because news media frequently target
      specific racial or ethnic audiences, some populations may receive different
      information, and it is unknown whether reporting equally informs all audiences
      about the options for care at the end of life. This study of news reporting
      compared "mainstream" (general market) media with African American media, which
      serves the largest minority group. The specific goal of this study was to
      determine whether these news media communicate differently about cure-directed
      cancer treatment and end-of-life alternatives. METHODS: This content analysis
      included 660 cancer news stories from online and print media that targeted either
      African American or mainstream audiences. The main outcome measures included
      whether reporting discussed adverse events of cancer treatment, cancer treatment
      failure, cancer death/dying, and end-of-life palliative or hospice care. RESULTS:
      Unadjusted and adjusted analyses indicated that the news stories in the African
      American media are less likely than those in mainstream media to discuss each of
      the topics studied. Comparing the proportions of news stories in mainstream
      versus African American media, 31.6% versus 13.6% discussed adverse events (odds
      ratio [OR], 2.92; 95% confidence interval [CI], 1.51-5.66; P = .001); 14.1%
      versus 4.2% mentioned treatment failure (OR, 3.79; 95% CI, 1.45-9.88; P = .006);
      and 11.9% versus 3.8% focused on death/dying (OR, 3.42; 95% CI, 1.39-8.38; P =
      .007). Finally, although very few news stories discussed end-of-life hospice or
      palliative care, all were found in mainstream media (7/396 vs 0/264). CONCLUSION:
      The African American news media sampled are less likely than mainstream news
      media to portray negative cancer outcomes and end-of-life care. Given media's
      segmented audiences, these findings raise concerns that not all audiences are
      being informed equally well. Because media content is modifiable, there may be
      opportunities to improve public cancer communication.

PMID- 21952923
TI  - Overexpression of the oncostatin M receptor in cervical squamous cell carcinoma
      cells is associated with a pro-angiogenic phenotype and increased cell motility
      and invasiveness.
AB  - Oncostatin M receptor (OSMR) shows frequent copy number gain and overexpression
      in advanced cervical squamous cell carcinoma (SCC). We used cell-based in vitro
      assays, RNA interference, and integrative gene expression profiling to
      investigate the functional significance of this observation. CaSki and SW756 were
      selected as representative cervical SCC cells that overexpressed OSMR, and ME180
      and MS751 as cells that did not. The STAT-dependent pro-angiogenic factors VEGF-A
      and ID1 were rapidly induced by OSM in CaSki/SW756 but not in ME180/MS751.
      However, rapid induction did occur in MS751 following forced OSMR overexpression,
      while depleting OSMR in CaSki abrogated VEGF-A expression. Conditioned medium
      from both CaSki and SW756 stimulated endothelial tube formation in vitro, effects
      that were inhibited by depleting OSMR in the SCC cells. For both CaSki and SW756,
      migration in a wound healing assay and invasion through Matrigel were stimulated
      by OSM and consistently inhibited by OSMR depletion. The phenotype was rescued by
      transfection with OSMR containing a silent mutation that provided specific siRNA
      resistance. Overall, there was a positive correlation between OSMR levels and
      invasiveness. We used gene expression profiling to identify genes induced by OSM
      in CaSki/SW756 but not in ME180/MS751. The most prominent gene ontology category
      groups for the differentially expressed genes were cell motility/invasion,
      angiogenesis, signal transduction, and apoptosis. We also profiled 23 cervical
      SCC samples, identifying genes that were differentially expressed in cases with
      OSMR overexpression versus those without. Integration of the datasets identified
      15 genes that showed consistent differential expression in association with OSMR
      levels in vitro and in vivo. We conclude that OSMR overexpression in cervical SCC
      cells provides increased sensitivity to OSM, which induces pro-malignant changes.
      OSMR is a potential prognostic and therapeutic target in cervical SCC. The genes
      that mediate OSM:OSMR effects will be valuable indicators of the effectiveness of
      antibody blockade in pre-clinical systems.

PMID- 21952924
TI  - Histone deacetylases are dysregulated in rheumatoid arthritis and a novel histone
      deacetylase 3-selective inhibitor reduces interleukin-6 production by peripheral
      blood mononuclear cells from rheumatoid arthritis patients.
AB  - OBJECTIVE: To characterize the role of histone deacetylase (HDAC) activity in
      rheumatoid arthritis (RA) and to evaluate the effects of MI192, a novel HDAC-3
      selective inhibitor, compared with the established nonselective HDAC inhibitor
      trichostatin A (TSA), on proinflammatory cytokine production. METHODS: Activity
      of HDAC and histone acetyltransferase was measured in peripheral blood
      mononuclear cells (PBMCs) from RA patients by spectrophotometric assay, prior to
      and after 12 weeks of etanercept therapy. The effects of HDAC inhibitor treatment
      on cytokine production in both RA and healthy PBMCs were assessed by enzyme
      linked immunosorbent assay. RESULTS: RA PBMCs exhibited significantly increased
      HDAC activity (P = 0.007) compared to PBMCs from healthy individuals, and the
      increase was unaltered after 12 weeks of etanercept therapy. TSA was a potent
      inhibitor of tumor necrosis factor (TNF) and interleukin-6 (IL-6) production in
      both RA and healthy PBMCs and of interferon-gamma (IFNgamma) production in
      healthy PBMCs; IFNgamma was not produced by RA PBMCs. MI192 inhibited TNF
      production at high concentrations and dose-dependently inhibited IL-6 in RA PBMCs
      but not healthy PBMCs, across a dose range of 10 MUM-5 nM. CONCLUSION: HDAC
      activity is dysregulated in RA PBMCs and is a potential target for therapeutic
      intervention, as it is not affected by conventional anti-TNF treatment with
      etanercept. Both the selective and the nonselective HDAC inhibitors (MI192 and
      TSA, respectively) were found to regulate cytokine production from PBMCs, but
      their effects were cell type and compound specific. HDAC inhibitors have
      potential in the treatment of RA, and HDAC-selective inhibition may improve the
      therapeutic margin of safety; however, further clinical characterization and
      evaluation for adverse effects is needed.

PMID- 21952925
TI  - A systematic review of microsurgical reconstruction of the jaws using
      vascularized fibula flap technique in patients with bisphosphonate-related
      osteonecrosis.
AB  - OBJECTIVE: The aim of this systematic review was to assess the role of
      microsurgical reconstruction of the jaws in patients with bisphosphonate-related
      osteonecrosis, and biological complications after an observation period of at
      least 12 months. MATERIAL AND METHODS: An electronic MEDLINE search supplemented
      by manual searching was conducted to identify studies reporting data of at least
      12 months observation on the microsurgical reconstruction of the jaws in patients
      with bisphosphonate-related osteonecrosis. RESULTS: Four studies resulted
      eligible for the analysis yielded. Three out of five studies were free of
      complications, with a success rate of 100% as no recurrence of osteonecrosis was
      registered. CONCLUSIONS: Microsurgical reconstruction of the jaws represents a
      valid treatment modality in patients with bisphosphonate-related osteonecrosis at
      3rd stage of the disease.

PMID- 21952926
TI  - Reconstruction of bony facial contour deficiencies with polymethylmethacrylate
      implants: case report.
AB  - Facial trauma can be considered one of the most serious aggressions found in the
      medical centers due to the emotional consequences and the possibility of
      deformity. In craniofacial surgery, the use of autologous bone is still the first
      choice for reconstructing bony defects or irregularities. When there is a
      shortage of donor bone or a patient refuses an intracranial operation,
      alloplastic materials such as polymethylmethacrylate (PMMA) can be used. The PMMA
      prosthesis can be pre-fabricated, bringing advantages such as reduction of
      surgical time, easy technical handling and good esthetic results. This paper
      describes the procedures for rehabilitating a patient with PMMA implants in the
      region of the face, recovering the facial contours and esthetics of the patient.

PMID- 21952927
TI  - Early treatment of Class III malocclusion: 10-year clinical follow-up.
AB  - Angle Class III malocclusion has been a challenge for researchers concerning
      diagnosis, prognosis and treatment. It has a prevalence of 5% in the Brazilian
      population, and may have a genetic or environmental etiology. This malocclusion
      can be classified as dentoalveolar, skeletal or functional, which will determine
      the prognosis. Considering these topics, the aim of this study was to describe
      and discuss a clinical case with functional Class III malocclusion treated by a
      two-stage approach (interceptive and corrective), with a long-term follow-up. In
      this case, the patient was treated with a chincup and an Eschler arch, used
      simultaneously during 14 months, followed by corrective orthodontics. It should
      be noticed that, in this case, initial diagnosis at the centric relation allowed
      visualizing the anterior teeth in an edge-to-edge relationship, thereby favoring
      the prognosis. After completion of the treatment, the patient was followed for a
      10-year period, and stability was observed. The clinical treatment results showed
      that it is possible to achieve favorable outcomes with early management in
      functional Class III malocclusion patients.

PMID- 21952929
TI  - [Imaging for intensive care medicine and emergency medicine].

PMID- 21952928
TI  - The phosphatidyl inositol 3 kinase-glycogen synthase kinase 3beta pathway
      mediates bilobalide-induced reduction in amyloid beta-peptide.
AB  - Bilobalide (BB), a sesquiterpenoid extract of Ginkgo biloba leaves, has been
      demonstrated to have neuroprotective effects. The neuroprotective mechanisms were
      suggested to be associated with modulation of intracellular signaling cascades
      such as the phosphatidyl inositol 3-kinase (PI3K) pathway. Since some members of
      intracellular signalling pathways such as PI3K have been demonstrated to be
      involved in amyloid precursor protein (APP) processing, the present study
      investigated whether BB has an influence on the beta-secretase-mediated APP
      cleavage via PI3K-dependent pathway. Using HT22 cells and SAMP8 mice (a
      senescence-accelerated strain of mice), this study showed that BB treatment
      reduced generation of two beta-secretase cleavage products of APP, the amyloid
      beta-peptide (Abeta) and soluble APPbeta (sAPPbeta), via PI3K-dependent pathway.
      Additionally, glycogen synthase kinase 3beta (GSK3beta) signaling might be
      involved in BB-induced Abeta reduction as a downstream target of the activated
      PI3K pathway. BB showed no significant effects on beta-site APP cleaving enzyme 1
      (BACE-1) or gamma-secretase but inhibited the beta-secretase activity of another
      protease cathepsin B, suggesting that BB-induced Abeta reduction was probably
      mediated through modulation of cathepsin B rather than BACE-1. Similarly,
      inhibition of GSK3beta did not affect BACE-1 activity but decreased cathepsin B
      activity, suggesting that the PI3K-GSK3beta pathway was probably involved in BB
      induced Abeta reduction. Increasing evidence suggests that decreasing Abeta
      production in the brain via modulation of APP metabolism should be beneficial for
      the prevention and treatment of Alzheimer's disease (AD). BB may offer such an
      approach to combat AD.

PMID- 21952930
TI  - Forensic odontology involvement in disaster victim identification.
AB  - Forensic odontology is one of three primary identifiers designated by Interpol to
      identify victims of mass casualty events. Forensic odontology is involved in all
      five phases-Scene, Postmortem, Antemortem, Reconciliation and Debrief. Forward
      planning, adequate funding, international cooperation and standardization are
      essential to guarantee an effective response. A Standard Operation Procedure
      should be utilized to maximize quality, facilitate occupation and health issues,
      maintain security and form a structure to the relief program. Issues that must be
      considered in the management of the forensic odontology component of disaster
      victim identification are given in "Appendix 1". Each stage of the disaster, from
      initial notification to debrief, is analyzed and a comprehensive checklist of
      actions suggested.

PMID- 21952931
TI  - Enantioselective synthesis of alpha-deuterium labelled chiral alpha-amino acids
      via dynamic kinetic resolution of racemic azlactones.
AB  - Catalytic dynamic kinetic resolution (DKR) of racemic azlactones with EtOD using
      squaramide-based dimeric cinchona alkaloid organocatalysts is shown to be a
      highly effective strategy for the preparation of enantiomerically pure alpha
      deuterated chiral alpha-amino acids.

PMID- 21952932
TI  - The role of monocytes and inflammation in the pathophysiology of heart failure.
AB  - There is growing evidence to support an important role of inflammation in the
      underlying pathophysiology of heart failure (HF). Indeed, inflammatory cytokine
      levels are well recognized to be increased in patients with left ventricular
      dysfunction and appear to have prognostic implications. Monocytes play a pivotal
      role in the inflammatory cascade and are a major source of both pro- and anti
      inflammatory cytokines. They are intimately involved in tissue damage and repair
      and an imbalance of these processes may have detrimental consequences for the
      failing myocardium. Importantly, monocytes comprise of distinct subsets with
      different cell surface markers and functional characteristics and this
      heterogeneity may be important in understanding their specific role in HF. In HF,
      monocyte activation involves interplay between pattern recognition molecules,
      endotoxins, cytokines, and acute phase proteins. Activated monocytes migrate to
      the myocardium in response to powerful chemokines, where they must then attach to
      the endothelial wall before infiltrating into the myocardium itself. This review
      article aims to discuss the role of monocytes and inflammation in HF, focusing on
      monocyte activation, mobilisation, recruitment and endothelial adherence, as well
      as the effects they may have on myocardial performance. The therapeutic
      modulation of inflammation and monocyte activation in HF treatment will also be
      reviewed.

PMID- 21952933
TI  - Bimetallic aluminum alkyl complexes as highly active initiators for the
      polymerization of epsilon-caprolactone.
AB  - Two dinuclear aluminum alkyl complexes supported by a piperazidine-bridged
      bis(phenolato) group were prepared, and both complexes exhibited extremely high
      activity for the ring-opening polymerization of epsilon-caprolactone. In the
      presence of benzyl alcohol (BnOH), the polymerization accelerated dramatically.

PMID- 21952934
TI  - ACE2 overexpression in the paraventricular nucleus attenuates angiotensin II
      induced hypertension.
AB  - AIMS: Angiotensin II (Ang II) has been shown to have both central and peripheral
      effects in mediating hypertension, for which the hypothalamic paraventricular
      nucleus (PVN) is an important brain cardio-regulatory centre. Angiotensin
      converting enzyme 2 (ACE2) has been identified as a negative regulator of the pro
      hypertensive actions of Ang II. Recent findings from our laboratory suggest that
      Ang II infusion decreases ACE2 expression in the PVN. In the present study, we
      hypothesized that ACE2 overexpression in the PVN will have beneficial effects in
      counteracting Ang II-induced hypertension. METHODS AND RESULTS: Male Sprague
      Dawley rats were used in this study. Bilateral microinjection of an adenovirus
      encoding hACE2 (Ad-ACE2) into the PVN was used to overexpress ACE2 within this
      region. Mean arterial pressure measured by radiotelemetry was significantly
      increased after 14 days in Ang II-infused (200 ng/kg/min) rats vs. saline-infused
      controls (162.9 +/- 3.6 vs. 102.3 +/- 1.5 mmHg). Bilateral PVN microinjection of
      Ad-ACE2 attenuated this Ang II-induced hypertension (130.2 +/- 5.7 vs. 162.9 +/-
      3.6 mmHg). ACE2 overexpression also significantly decreased AT(1)R and ACE
      expression and increased AT(2)R and Mas expression in the PVN. Additionally, ACE2
      overexpression in the PVN attenuated the Ang II-induced increase in the
      expression of the pro-inflammatory cytokines tumour necrosis factor-alpha,
      interleukin (IL)-1beta and IL-6 in the PVN. CONCLUSION: Our findings suggest that
      attenuation of pro-inflammatory cytokines in the PVN in combination with the
      shift of the renin-angiotensin system towards the anti-hypertensive axis
      (ACE2/Ang-(1-7)/Mas) may be responsible for the overall beneficial effects of
      ACE2 overexpression in the PVN on the Ang II-induced hypertensive response.

PMID- 21952935
TI  - Candesartan restored cardiac Hsp72 expression and tolerance against reperfusion
      injury in hereditary insulin-resistant rats.
AB  - AIMS: We tested the hypothesis that candesartan, an angiotensin II (AII) type 1
      receptor antagonist, would restore the depressed phosphatidylinositol 3 (PI3)
      kinase-dependent Akt phosphorylation, an essential signal to induce heat-shock
      protein 72 (Hsp72) in response to hyperthermia, in Otsuka Long-Evans Tokushima
      fatty (OLETF) rats. METHODS AND RESULTS: At 14 weeks of age, male OLETF rats and
      Long-Evans Tokushima Otsuka (LETO) rats were treated with candesartan (0.25
      mg/kg/day) for 2 weeks. Thereafter, hyperthermia (43 degrees C for 20 min) was
      applied. We observed the following: (i) Candesartan did not improve insulin
      sensitivity in OLETF rats. (ii) Candesartan restored depressed PI3 kinase
      dependent Akt phosphorylation and Hsp72 expression in OLETF rat hearts. (iii)
      Cardiac ventricular tissue contents of AII were greater in OLETF rats, which were
      suppressed by candesartan. (iv) Cardiac levels of phosphatase and tensin
      homologue deleted on chromosome 10 (PTEN) phosphorylation were greater in OLETF
      rats, which were suppressed by candesartan. In cultured cardiomyocytes,
      application of AII induced PTEN phosphorylation, which was suppressed by
      candesartan. (v) In high-fat diet insulin-resistant rats, similar results were
      observed with respect to Hsp72 expression, Akt phosphorylation and PTEN
      phosphorylation. (vi) In isolated, perfused heart experiments, reperfusion
      induced cardiac functional recovery was suppressed in OLETF rat hearts, which was
      improved by candesartan. CONCLUSION: Our results suggest that the depression of
      PI3 kinase-dependent Akt activation in response to hyperthermia in OLETF rats can
      be restored by candesartan. Substantial activation of the renin-angiotensin
      system, represented by increased myocardial AII content and subsequent PTEN
      phosphorylation, may underlie the pathogenesis which is ameliorated by
      candesartan.

PMID- 21952936
TI  - Mapping QTLs for tissue culture response in soybean (Glycine max (L.) Merr.).
AB  - Quantitative trait loci (QTLs) that control the tissue culture response in
      soybean were detected by using 184 recombinant inbred lines (RILs) derived from
      two varieties: Kefeng No.1 and Nannong 1138-2. The molecular map consisting of
      834 molecular markers using this population covered space 2307.83 cM of the
      genome throughout 24 linkage groups. The performance of tissue culture in soybean
      was evaluated by two indices: callus induction frequency (CIF) and somatic
      embryos initiation frequency (SEIF). They were expressed as the number of
      explants producing callus/ the number of total explants and the number of
      explants producing somatic embryos/ the number of total explants, respectively.
      The RIL lines showed continuous segregation for both indices. With the composite
      interval mapping (CIM) described in Windows QTL Cartographer Version 2.5, three
      quantitative trait loci (QTLs) were identified for the frequency of callus
      induction, on chromosomes B2 and D2, accounting for phenotypic variation from
      5.84% to 16.60%; four QTLs on chromosome G were detected for the frequency of
      somatic embryos initiation and explained the phenotypic variation from 7.79% to
      14.16%. The information of new QTLs identified in the present study will
      contribute to genetic improvement of regeneration traits with marker-assisted
      selection (MAS) in soybean.

PMID- 21952937
TI  - Pairwise verlet lists: combining cell lists and verlet lists to improve memory
      locality and parallelism.
AB  - Verlet lists, which are commonly used in many particle-based simulations, are not
      suited for modern, shared-memory parallel multicore architectures. In this
      article, we introduce pairwise Verlet lists: local Verlet lists containing only
      interacting particle pairs between a pair of neighboring computational cells. We
      show that these pairwise Verlet lists are more efficient and scale much better
      than the traditional global Verlet list, both on a single processor as well as on
      multiple shared-memory cores. The improved performance on a single core makes
      them an interesting option for distributed-memory simulations as well.

PMID- 21952938
TI  - Do work ability and job involvement channel later personal goals in retirement?
      An 11-year follow-up study.
AB  - OBJECTIVE: The present study investigates the role of work ability and job
      involvement in personal life goals later in retirement. METHODS: The study is
      based on longitudinal research on Finnish employees working in managerial
      positions. At the study baseline (in 1996), 120 employed managers responded to a
      questionnaire regarding their work ability and job involvement, and 11 years
      later (in 2007) when they were retired, they responded to an open-ended question
      regarding their personal goals. The retired participants were 58-76 years old (M
      = 66 years), and they had been retired for 1-10 years (M = 4.3 years, SD = 2.9).
      RESULTS: On the basis of the participants' responses to the open-ended question,
      six main content categories of personal goals were formed. According to these
      categories, the personal goals in retirement focused on (1) hobbies and leisure
      time, (2) social relationships, (3) health and well-being, (4) housing and
      finance, (5) self-development and ideology, and (6) other activities. The
      managers with better work ability and job involvement at the baseline of the
      study had fewer personal goals related to health and well-being later in
      retirement. In addition, better work ability predicted more personal goals
      related to self-development and ideology views. CONCLUSIONS: The preceding work
      ability and job involvement seem to channel personal goal pursuit in retirement.
      Thus, sustaining employees' work ability and job involvement are not only
      essential for developing employees' ability to cope with work demands but also
      for their functional capacity in their later stages of life, such as in
      retirement.

PMID- 21952939
TI  - Inactivation of phosphomannose isomerase gene abolishes sporulation and
      antibiotic production in Streptomyces coelicolor.
AB  - Phosphomannose isomerases (PMIs) in bacteria and fungi catalyze the reversible
      conversion of D-fructose-6-phosphate to D-mannose-6-phosphate during biosynthesis
      of GDP-mannose, which is the main intermediate in the mannosylation of important
      cell wall components, glycoproteins, and certain glycolipids. In the present
      study, the kinetic parameters of PMI from Streptomyces coelicolor were obtained,
      and its function on antibiotic production and sporulation was studied. manA
      (SCO3025) encoding PMI in S. coelicolor was deleted by insertional inactivation.
      Its mutant (S. coelicolor?manA) was found to exhibit a bld-like phenotype.
      Additionally, S. coelicolor?manA failed to produce the antibiotics actinorhodin
      and red tripyrolle undecylprodigiosin in liquid media. To identify the function
      of manA, the gene was cloned and expressed in Escherichia coli BL21 (DE3). The
      purified recombinant ManA exhibited PMI activity (K(cat)/K(m) (mM(-1) s(-1) =
      0.41 for D-mannose-6-phosphate), but failed to show GDP-D-mannose
      pyrophosphorylase [GMP (ManC)] activity. Complementation analysis with manA from
      S. coelicolor or E. coli resulted in the recovery of bld-like phenotype of S.
      coelicolor?manA. SCO3026, another ORF that encodes a protein with sequence
      similarity towards bifunctional PMI and GMP, was also tested for its ability to
      function as an alternate ManA. However, the purified protein of SCO3026 failed to
      exhibit both PMI and GMP activity. The present study shows that enzymes involved
      in carbohydrate metabolism could control cellular differentiation as well as the
      production of secondary metabolites.

PMID- 21952940
TI  - LysA2, the Lactobacillus casei bacteriophage A2 lysin is an endopeptidase active
      on a wide spectrum of lactic acid bacteria.
AB  - The lysin gene (lysA2) of the Lactobacillus casei bacteriophage A2 was cloned and
      expressed in Escherichia coli. LysA2 is an endopeptidase that hydrolyzes the bond
      between the terminal D: -alanine of the peptidoglycan tetrapeptide and the
      aspartic acid residue that forms the bridge with the L: -lysine of a neighboring
      peptidoglycan chain, characteristic of Gram-positive bacteria included into the
      A4 peptidoglycan subgroup. This includes most lactobacilli, Lactococcus lactis,
      Pediococcus acidilactici, and Pediococcus pentosaceus, the walls of all of which
      were substrates for the enzyme. Specific binding of LysA2 to the wall of these
      bacteria is mediated by its C-terminal moiety, does not need the N-terminal
      catalytic domain for recognition, and is stable: at least 88% of the molecules
      were still bound to L. casei after 3 days in phosphate buffer at 4 degrees C. The
      enzyme acts as a monomer, is active at pH values between 4 and 6, and at
      temperatures ranging between 18 degrees C and 50 degrees C while being
      independent of divalent cation addition. The enzyme showed strong resistance to
      incubation at high and low pH values but became progressively inactivated at 50
      degrees C and above. LysA2 is bactericidal, the viability of L. casei cultures
      dropping to 1% in 10 min, under the standard conditions used for the enzymatic
      assay.

PMID- 21952941
TI  - Phosphorus removal characteristics of granular and flocculent sludge in SBR.
AB  - Aerobic granulation technology has become a novel biotechnology for wastewater
      treatment. However, the distinct properties and characteristics of phosphorus
      removal between granules and flocculent sludge are still sparse in enhanced
      biological phosphorus removal process. Two identical sequencing batch reactors
      (SBRs) were operated to compare phosphorus removal performance with granular
      sludge (R1) and flocculate activated sludge (R2). Results indicated that the
      start-up period was shorter in R2 than R1 for phosphorus removal, which made R2
      reach the steady-state condition on day 21, while R1 was on day 25, and R2
      released and took up more phosphorus than R1. As a result, the phosphorus removal
      was around 90% in R2 while 80% in R1 at the steady-state system. The special
      phosphorus release rate and special phosphorus uptake rate were 8.818 mg P/g
      volatile suspended solids (VSS)/h and 9.921 mg P/g VSS/h in R2, which were
      consistently greater than those (0.999 and 3.016 mg P/g VSS/h) in R1. The
      chemical oxygen demand removal in two reactors was similar. The granular SBR had
      better solid-separation performance and higher removal efficiency of NH (4) (+) 
      N than flocculent SBR. Denaturing gradient gel electrophoresis of PCR-amplified
      16S rDNA fragment analysis revealed that the diversity and the level of
      phosphorus-accumulating bacteria in flocculent sludge were much more than those
      in the granular sludge.

PMID- 21952942
TI  - NLRP3 inflammasome-mediated neutrophil recruitment and hypernociception depend on
      leukotriene B(4)  in a murine model of gout.
AB  - OBJECTIVE: Deposition of monosodium urate monohydrate (MSU) crystals in the
      joints promotes an intense inflammatory response and joint dysfunction. This
      study evaluated the role of the NLRP3 inflammasome and 5-lipoxygenase (5-LOX)
      derived leukotriene B(4)  (LTB(4) ) in driving tissue inflammation and
      hypernociception in a murine model of gout. METHODS: Gout was induced by
      injecting MSU crystals into the joints of mice. Wild-type mice and mice deficient
      in NLRP3, ASC, caspase 1, interleukin-1beta (IL-1beta), IL-1 receptor type I (IL
      1RI), IL-18R, myeloid differentiation factor 88 (MyD88), or 5-LOX were used.
      Evaluations were performed to assess neutrophil influx, LTB(4)  activity,
      cytokine (IL-1beta, CXCL1) production (by enzyme-linked immunosorbent assay),
      synovial microvasculature cell adhesion (by intravital microscopy), and
      hypernociception. Cleaved caspase 1 and production of reactive oxygen species
      (ROS) were analyzed in macrophages by Western blotting and fluorometric assay,
      respectively. RESULTS: Injection of MSU crystals into the knee joints of mice
      induced neutrophil influx and neutrophil-dependent hypernociception. MSU crystal
      induced neutrophil influx was CXCR2-dependent and relied on the induction of
      CXCL1 in an NLRP3/ASC/caspase 1/IL-1beta/MyD88-dependent manner. LTB(4)  was
      produced rapidly after injection of MSU crystals, and this was necessary for
      caspase 1-dependent IL-1beta production and consequent release of CXCR2-acting
      chemokines in vivo. In vitro, macrophages produced LTB(4)  after MSU crystal
      injection, and LTB(4)  was relevant in the MSU crystal-induced maturation of IL
      1beta. Mechanistically, LTB(4)  drove MSU crystal-induced production of ROS and
      ROS-dependent activation of the NLRP3 inflammasome. CONCLUSION: These results
      reveal the role of the NLRP3 inflammasome in mediating MSU crystal-induced
      inflammation and dysfunction of the joints, and highlight a previously
      unrecognized role of LTB(4)  in driving NLRP3 inflammasome activation in response
      to MSU crystals, both in vitro and in vivo.

PMID- 21952943
TI  - Beneficial effects of albuterol in congenital endplate acetylcholinesterase
      deficiency and Dok-7 myasthenia.
AB  - INTRODUCTION: Congenital myasthenic syndromes (CMS) are disabling but treatable
      disorders. Anticholinesterase therapy is effective in most of them, but is
      contraindicated in endplate (EP) acetylcholinesterase (AChE) deficiency, the slow
      channel syndrome, Dok-7 myasthenia, and beta(2) -laminin deficiency, and is not
      useful in CMS due to defects in muscle-specific kinase (MuSK), agrin, and
      plectin. EP AChE, Dok-7, and beta(2)-laminin deficiencies respond favorably to
      ephedrine, but ephedrine can no longer be prescribed in the USA. METHODS: We used
      albuterol, another sympathomimetic agent, to treat 3 patients with EP AChE
      deficiency and 15 with Dok-7 myasthenia. Response to therapy was evaluated by a 9
      point questionnaire pertaining to activities of daily life. RESULTS: Comparison
      of the pre- and posttreatment responses indicated a beneficial response to
      albuterol (P < 0.001) in both patient groups. The adverse effects of therapy were
      like those of ephedrine. CONCLUSION: Our observations should spur controlled,
      prospective clinical trials of albuterol in these as well as other CMS.

PMID- 21952944
TI  - Peripheral blood reverse transcription PCR assay for prostate stem cell antigen
      correlates with androgen-independent progression in advanced prostate cancer.
AB  - Recent studies show that prostate stem cell antigen (PSCA) mRNA positivity in
      peripheral blood correlates with disease progression in prostate cancer (PCa).
      Our study is to evaluate the association between peripheral blood PSCA status and
      androgen-independent progression (AIP) in a cohort of patients with advanced PCa
      under androgen deprivation therapy (ADT). PSCA mRNA was measured by reverse
      transcriptase polymerase chain reaction (RT-PCR) assay in peripheral blood
      samples from 116 patients with locally advanced or metastatic PCa who were
      treated with primary ADT and from 40 healthy controls. The Kaplan-Meier and the
      Cox proportional hazards methods were used to assess potential predictors of AIP.
      Pretreatment RT-PCR-PSCA was positive in 37 (31.9%) of 116 patients. All healthy
      volunteers were negative for PSCA mRNA. Although seven (14.9%) of 47 patients
      with Gleason score <=7 were PSCA positive, 30 (43.5%) of 69 patients with Gleason
      score >7 were PSCA positive (p = 0.016). PSCA mRNA was detected in 28 (58.3%) of
      48 patients with metastatic PCa, compared to nine (13.2%) of 68 patients with
      locally advanced disease (p = 0.012). AIP developed in 59 (50.9%) patients during
      a median follow-up period of 35.4 months (range: 4-78 months). Patients with PSCA
      negativity experienced significantly longer remissions compared to those with
      PSCA positivity (log-rank test: p < 0.001). Multivariate Cox regression analysis
      further demonstrated that PSCA positivity had a significantly increased risk of
      AIP (HR = 4.303, 95% CI: 3.761-7.482, p < 0.001). Pretreatment RT-PCR PSCA
      positivity in peripheral blood independently signals the presence of AIP in
      patients with advanced PCa treated with ADT.

PMID- 21952945
TI  - Learning styles in otolaryngology fellowships.
AB  - OBJECTIVES/HYPOTHESIS: Previous studies have identified a predominant learning
      style in trainees from different specialties, more recently in otolaryngology
      residents. The purpose of our study was to determine a predominant learning style
      within otolaryngology fellowships and to identify any differences between
      otolaryngology fellows and residents. STUDY DESIGN: We conducted a survey of
      otolaryngology fellows at 25 otolaryngology fellowship programs accredited by the
      Accreditation Council for Graduate Medical Education. METHODS: We emailed Kolb's
      Learning Style Index version 3.1 to 16 pediatric otolaryngology (PO) and 24
      otology/neurotology (ON) fellows. This index is a widely used 12-item
      questionnaire. The participants answered each item in the questionnaire as it
      applied to their preferred learning style: accommodating, converging, diverging,
      or assimilating. Results were then analyzed and compared between each
      subspecialty and the previously reported preferred styles of otolaryngology
      residents. RESULTS: Ten PO and 20 ON fellows completed the survey, with an
      overall response rate of 75%. PO and ON fellows (60% of each group) preferred a
      learning style that was "balanced" across all four styles. For ON fellows, 35%
      preferred converging and 5% preferred accommodating styles. For PO fellows,
      converging and accommodating styles accounted for 20% each. CONCLUSIONS: It was
      previously reported that 74.4% of otolaryngology residents prefer either
      converging or accommodating styles. We believe that the fellowship training
      environment calls for fellows to use more than one learning style to become
      proficient physicians, hence the trend toward potentially developing a balanced
      style when at this level.

PMID- 21952946
TI  - Malignant Polyp in a Colonic Diverticulum: a Rare Cause of Diverticular
      Hemorrhage.

PMID- 21952948
TI  - Omission of radiation therapy after breast-conserving surgery in the United
      States: a population-based analysis of clinicopathologic factors.
AB  - BACKGROUND: Radiation therapy (RT) after breast-conserving surgery (BCS) is
      associated with a significant reduction in ipsilateral breast tumor recurrence
      and breast cancer mortality rates in patients with early stage breast cancer. The
      authors of this report sought to determine which patients with breast cancer do
      not receive RT after BCS in the United States. METHODS: The Surveillance,
      Epidemiology, and End Results registry was used to determine the rates of RT
      after BCS for women with stage I through III breast cancer in the United States
      from 1992 through 2007. A multivariate analysis was performed to identify
      independent predictors of omission of RT. RESULTS: In total, 294,254 patients
      with invasive, nonmetastatic breast cancer were identified who underwent surgery
      from 1992 through 2007. Most patients (57%) underwent BCS; among those, 21.1% did
      not receive RT after BCS. The omission of RT increased significantly from 1992
      (15.5%) to 2007 (25%). The receipt of RT also decreased significantly for
      patients with increased cancer stage, age <55 years, high-grade tumors, large
      tumors, positive or untested lymph node status, African American or Hispanic
      race, and negative or unknown estrogen receptor status. Significant geographic
      variation was observed in the rates of RT after BCS. CONCLUSIONS: The omission of
      RT after BCS was more common in recent years, especially among women who had an
      increased risk of breast cancer recurrence. This trend represents a serious
      health care concern because of the potential increased risk of local recurrence
      and breast cancer mortality.

PMID- 21952947
TI  - Gain-of-function mutant p53 but not p53 deletion promotes head and neck cancer
      progression in response to oncogenic K-ras.
AB  - Mutations in p53 occur in over 50% of the human head and neck squamous cell
      carcinomas (SCCHN). The majority of these mutations result in the expression of
      mutant forms of p53, rather than deletions in the p53 gene. Some p53 mutants are
      associated with poor prognosis in SCCHN patients. However, the molecular
      mechanisms that determine the poor outcome of cancers carrying p53 mutations are
      unknown. Here, we generated a mouse model for SCCHN and found that activation of
      the endogenous p53 gain-of-function mutation p53$^{?rm{R172H}}$, but not deletion
      of p53, cooperates with oncogenic K-ras during SCCHN initiation, accelerates oral
      tumour growth, and promotes progression to carcinoma. Mechanistically, expression
      profiling of the tumours that developed in these mice and studies using cell
      lines derived from these tumours determined that mutant p53 induces the
      expression of genes involved in mitosis, including cyclin B1 and cyclin A, and
      accelerates entry in mitosis. Additionally, we discovered that this oncogenic
      function of mutant p53 was dependent on K-ras because the expression of cyclin B1
      and cyclin A decreased, and entry in mitosis was delayed, after suppressing K-ras
      expression in oral tumour cells that express p53$^{?rm{R172H}}$. The presence of
      double-strand breaks in the tumours suggests that oncogene-dependent DNA damage
      resulting from K-ras activation promotes the oncogenic function of mutant p53.
      Accordingly, DNA damage induced by doxorubicin also induced increased expression
      of cyclin B1 and cyclin A in cells that express p53$^{?rm{R172H}}$. These
      findings represent strong in vivo evidence for an oncogenic function of
      endogenous p53 gain-of-function mutations in SCCHN and provide a mechanistic
      explanation for the genetic interaction between oncogenic K-ras and mutant p53.

PMID- 21952949
TI  - Asymmetric first total syntheses and assignment of absolute configuration of
      oxazinin-5, oxazinin-6 and preoxazinin-7.
AB  - Asymmetric first total syntheses of the unprecedented toxins oxazinin-5, oxazinin
      6 and preoxazinin-7 have been achieved from a common key intermediate 18, derived
      from a regiocontrolled Sharpless asymmetric aminohydroxylation and oxa-Michael
      reaction, which in addition to confirming the structure also established the
      absolute configuration of the natural products. On the way an expeditious
      synthesis of a metabolite bursatellin was completed in 8 steps.

PMID- 21952950
TI  - Targeting integrins and enhanced permeability and retention (EPR) effect for
      optical imaging of oral cancer.
AB  - BACKGROUND AND OBJECTIVES: Near-infrared (NIR) fluorescence optical imaging is a
      promising technique to assess the tumor margins during cancer surgery. This
      technique requires targeting by specific fluorescence agents to differentiate
      tumor from normal surrounding tissue. We assessed the feasibility of cancer
      detection using NIR fluorescence agents that target either alphavbeta3 integrins
      or the enhanced permeability and retention (EPR) effect in an orthotopic mouse
      model of oral cancer. METHODS: Binding of the integrin-targeted agent to tumor
      cells was assessed in vitro. Oral cancer was induced in 6 BALB/c nu/nu mice by
      submucosal inoculation of human OSC19-luc cells into the tongue. Tumor growth was
      followed with bioluminescence imaging. A combination of agents targeting
      integrins or EPR effect was injected followed by fluorescence imaging in vivo and
      ex vivo after resection of the tongues. RESULTS: Oral cancer was clearly
      demarcated in vitro; in vivo; and on histological analysis with sufficient tumor
      to-background ratios of the contrast agents. CONCLUSION: This study demonstrates
      the feasibility of optical imaging of oral squamous cell carcinoma based on
      targeting of alphavbeta3 integrins and the EPR effect. Once these NIR
      fluorescence agents become available for clinical testing, optical image-guided
      surgery could reduce residual disease after oral cancer surgery.

PMID- 21952951
TI  - The efficacy and safety of liraglutide.
AB  - AIM OF THE REVIEW: To systematically analyze the efficacy and safety of
      liraglutide for the treatment of diabetes mellitus in comparison to other mono-
      and combination therapies. METHOD: PubMed (any date) and EMBASE (all years)
      search was conducted with liraglutide as a search term. Phase III clinical trials
      retrieved by the two databases and resources posted in Drug@FDA website were
      evaluated with regard to outcomes of efficacy and safety. RESULTS: Eight Phase
      III clinical studies compared the efficacy and safety of liraglutide to other
      monotherapies or combinations. Liraglutide as monotherapy in doses of 0.9 mg or
      above showed a significantly superior reduction in HbA1C compared to
      monotherapies with glimepiride or glyburide. When liraglutide was used as add-on
      therapy to glimepiride in doses of 1.2 mg or above, the reduction of HbA1C was
      greater than that in the combination therapy of glimepiride and rosiglitazone.
      However, liraglutide as add-on therapy to metformin failed to show benefit over
      combination of metformin and glimepiride. Triple therapy of using liraglutide in
      addition to metformin plus either glimepiride or rosiglitazone resulted in
      additional benefit in HbA1C reduction. Most common adverse events were
      gastrointestinal disturbance such as nausea, vomit, diarrhea, and constipation.
      During the eight clinical studies, six cases of pancreatitis and five cases of
      cancer were reported in liraglutide arm, whereas there was one case of each of
      pancreatitis in exenatide and glimepiride arms, respectively, and one case of
      cancer in metformin plus sitagliptin arm. CONCLUSION: Liraglutide is a new
      therapeutic option to improve glycemic control in patients with type 2 diabetes.
      However, the present lack of evidence of durability of efficacy and long-term
      safety appear to limit its utility in the general treatment of type 2 diabetes at
      this time.

PMID- 21952953
TI  - Perceptions and attitudes of Jordanian paediatricians towards off-label
      paediatric prescribing.
AB  - OBJECTIVE: To assess current experiences and attitudes of hospital based
      paediatricians towards off-label medicine prescribing. SETTING: Paediatric
      hospital wards and out-patient clinics. DESIGN: A prospective, questionnaire
      based study. RESULTS: A 30 item questionnaire was sent to 300 hospital based
      paediatricians and 250 (83%) were returned completed. Over 69% of responders were
      familiar with the term off-label medicines. However, only 28% were knowingly
      prescribing off-label medicines to children. The majority of respondents (90%)
      expressed concerns about the safety and efficacy of off-label medicines. Only 15%
      had observed Adverse Drug Reactions, and 31% a treatment failure. The vast
      majority of respondents (83%) did not obtain informed consent or tell parents
      they were prescribing off label medicines to their children. CONCLUSIONS: Off
      label prescribing of medicines to children is a familiar concept to the majority
      of paediatricians in Jordan although only a smaller number are aware that it is
      common in their practice. Respondents showed concern about off label prescribing,
      although the majority do not consider it necessary to inform parents. More
      comprehensive research is needed in this area in Jordan and other Middle Eastern
      countries.

PMID- 21952954
TI  - Plasmon hybridization and strong near-field enhancements in opposing nanocrescent
      dimers with tunable resonances.
AB  - A novel dimer nanostructure architecture featuring two symmetrically arranged
      crescents with opposing, nanometer-sized tips in close proximity is fabricated by
      colloidal lithography. This structure exhibits a strong and highly localized
      electrical near-field in the gap region between the tips. The close proximity of
      the tips in the nanocrescent dimers leads to a strong coupling process which
      generates new hybrid plasmon modes with different optical resonances. The optical
      properties of both single crescents and dimeric double crescent arrangements are
      investigated in detail, and correlations between resonance wavelengths and
      geometrical parameters are established. We apply plasmon hybridization theory to
      explain the spectral shifts between coupled and uncoupled crescent nanostructures
      based on simple geometric arguments for all polarization-dependent resonances.
      Computer simulations support the hybridization model and were further used to
      examine and compare the near-field enhancement of single and opposing double
      crescents. For close proximities of the two opposing crescents, a strong near
      field with an enhancement factor of approximately 53 was detected. Compared to
      the near-field enhancement of approximately 20 for single crescents, the
      proximity of the second crescents further increases the near-field to more than
      seven times the initial value.

PMID- 21952952
TI  - Clinical pharmacists and basic scientists: do patients and physicians need this
      collaboration?
AB  - The aim of this commentary is to highlight the vital and beneficial role that
      pharmacists and inter-professional collaborative practice play in patient care
      from the economic, humanistic, efficacy, and safety perspectives. Pharmacists,
      particularly those with an in-depth knowledge of the basic pharmaceutical
      sciences, recognize the need to collaborate with other healthcare professions and
      understand the importance of combining all of the components of their education
      into a well-rounded, comprehensive clinical practice. Indeed, there is ample
      evidence in the literature that pharmacists equipped with a solid foundation in
      basic pharmaceutical science, coupled with clinical knowledge and skills can,
      more effectively, contribute to pharmacotherapy and patient care, particularly in
      a collaborative practice setting. Consequently, the burden on pharmacy education
      is to maintain its emphasis on the basic sciences while promoting the application
      of these sciences in clinical practice, in the Pharm. D. curriculum. This is a
      goal that can also be achieved through inter-professional educational approaches.

PMID- 21952955
TI  - Oviposition behavior of Grapholita molesta Busck (Lepidoptera: Tortricidae) at
      different temperatures.
AB  - Cultivation of temperate-climate fruits is economically important for Brazil.
      Grapholita molesta Busck is a pest that causes damage to apples, peaches, plums,
      and pears growing in different micro-regions of southern Brazil, and
      understanding its reproductive behavior is essential to develop control
      strategies. The objective of this study was to ascertain the influence of
      different temperatures (13, 16, 19, 22, and 25oC) on the oviposition behavior of
      G. molesta. Females of G. molesta were placed in individual plastic containers,
      and the pre-oviposition period and the number of eggs laid were assessed until
      adult death. Temperature influenced the pre-oviposition period, and females kept
      at 22o were the first to lay their eggs. Oviposition occurred over a longer
      period of time at 13oC than at the higher temperatures. The highest total number
      of eggs was obtained at 19oC, with the mean daily oviposition being directly
      proportional to the temperature. There was a negative interaction between the pre
      oviposition period and the total number of eggs laid by females. The most
      suitable temperature for oviposition of G. molesta was 19oC.

PMID- 21952956
TI  - Haplotype identification within Spodoptera frugiperda (J.E. Smith) (Lepidoptera:
      Noctuidae) corn and rice strains from Colombia.
AB  - The fall army worm Spodoptera frugiperda (Smith) is a migratory important pest of
      corn, sorghum, rice, grass and bermudagrass in North and South America. This
      species has diverged into two genetically differentiated but morphologically
      identical strains, "the rice" and "the corn". They have been analyzed by
      sequencing the genes cytochrome oxydase I, II and ITS1 from populations from the
      United States and Brazil. However, no such studies were performed in Colombia. In
      here, we identified 43 haplotypes by sequencing a fragment of the COI gene from
      102 individuals, of which 40 had already been identified as the "corn" and "rice"
      strains or to their hybrids from Tolima, and the rest were collected from corn,
      cotton, sorghum, grass and rice fields in other regions of Colombia. The corn
      strain haplotype H1 was the most frequently found in this country, representing
      the main target for FAW monitoring programs. AMOVA analysis confirmed the
      population structure between Colombian and North American S. frugiperda
      haplotypes (F(ST) = 0.76812, P < 0.001), but not within the different Colombian
      regions, suggesting high gene flow within the country. The ML trees obtained for
      Tolima and for Colombia as a whole did not generate clustering amongst S.
      frugiperda sequences, neither via host-plant association nor by geographical
      areas. The minimum spanning network for Colombia corroborated our finding that
      the haplotype H1 has the highest frequency in the country. Our data suggest that
      haplotype frequency determination will be useful in the establishment of a
      monitoring system for this species.

PMID- 21952957
TI  - Flower-visiting insects of five tree species in a restored area of semideciduous
      seasonal forest.
AB  - The reinstatement of biodiversity and ecological processes must be the major goal
      in restoration projects, which requires the establishment of biological
      interactions in addition to native plant population recovery. Therefore, we
      assessed the flower visitors of five tree species in a restored area of
      Semideciduous Seasonal Forest, in Ribeirao Preto, SP, Brazil. The specimens were
      collected using entomological net on flowers of Acacia polyphylla, Aegiphila
      sellowianna, Croton floribundus, Croton urucurana and Schinus terebinthifolius
      from October 2007 to September 2008. A total of 139 insect species belonging to
      five orders were collected. Hymenoptera was the most diverse order collected.
      From a total of 37 families, Vespidae (15 species), Cabronidae (12), Apidae (10),
      Halictidae (10), Syrphidae (12), Tachinidae (6) and Hesperidae (7) were the
      richest ones. Schinus terebinthifolius flowers presented the most abundant and
      diverse insect visitors (60), suggesting it is an important attractive species to
      the fauna in restoration programs. Our data suggest that mutualistic interactions
      between some of these plants and their flower-visiting insects may be in a
      reinstatement process, and will support the design and monitoring of future
      restoration efforts.

PMID- 21952958
TI  - Nutrient flux associated with the emergence of Quesada gigas Olivier (Hemiptera:
      Cicadidae) in an urban ecosystem.
AB  - Large-bodied arthropods, such as cicadas, can be able to reallocate significant
      amounts of nutrients during adult emergence. Evidence suggests that Quesada gigas
      Olivier emergence constitutes an important nutrient flux from belowground to
      aboveground. The purpose of this study was to estimate the amount of nitrogen,
      proteins, and lipids resulting from the emergence of Q. gigas in an urban
      ecosystem in Central Brazil. Adult specimens captured from September to November
      2006 were weighed and submitted to biochemical analysis. Population density was
      approximately 4,200 individuals per hectare. Mean individual dry mass was 1.03 g
      and contained 12.6% proteins, 8.4% lipids, and 5% nitrogen. Total biomass input
      from the species was 4.3 kg ha(-1) y(-1), with a consequent annual reallocation
      of approximately 545 g of proteins, 363 g of lipids, and 216 g of nitrogen per
      hectare. The data obtained suggest that Q. gigas emergence can cause significant
      translocation of nutrients from belowground to aboveground, and is therefore an
      important biological event for ecosystem function.

PMID- 21952959
TI  - Relocation of Croton sonderianus (Euphorbiaceae) seeds by Pheidole fallax Mayr
      (Formicidae): a case of post-dispersal seed protection by ants?
AB  - Although seed dispersal by ants might reduce seed predation near the parent
      plants, predation on discarded seeds clustered on nest refuse piles may reduce
      any initial benefit provided by seed removal. Here we examine the fate of Croton
      sonderianus seeds that were discarded by Pheidole fallax Mayr ants on their nest
      refuses in caatinga vegetation of northeast Brazil. We collected all seeds
      discarded in refuse piles of 20 nests and within a radius of 50 cm from their
      borders, and examined them for evidence of predation. A total of 3,017 seeds were
      recorded either located in the P. fallax refuse piles (89.1%) or nest vicinity
      (10.9%). Predation was three fold higher in nest vicinity as compared to refuse
      piles. By removing seeds from beneath parent plants and relocating then to refuse
      piles, P. fallax is possibly providing double protection services for C.
      sonderianus seeds. Our findings represent the first evidence for predator
      avoidance as benefit for plants resulting from ant seed-dispersal in the
      neotropics.

PMID- 21952960
TI  - Description and key to the fifth-instars of some Cicadas (Hemiptera: Cicadidae)
      associated with coffee plants in Brazil.
AB  - Fifth-instars of the cicada species Dorisiana drewseni (Stal), Dorisiana viridis
      (Olivier), Fidicina mannifera (Fabricius), Fidicinoides pronoe (Walker) and
      Carineta fasciculata (Germar) are described and illustrated. Moreover, a key to
      the nymphs of these species along with Quesada gigas (Olivier) is also provided.

PMID- 21952961
TI  - New species of Tetramorium Mayr (Hymenoptera: Formicidae) from Puebla State,
      Mexico.
AB  - Tetramorium notomelanum sp. n. is described from the Tehuacan Valley, state of
      Puebla, Mexico. Its distribution and relation with other species of the tortuosum
      group is discussed. The new species of Tetramonium is described from workers, and
      distinguished from others of the group by several characters: i) black coloration
      of the body; ii) size: T. notomelanum sp. n. is smaller than T. hispidum
      (Wheeler), T. mexicanum Bolton and T.spinosum (Pergande), but larger than T.
      bicolorum Vasquez-Bolanos and T. placidum Bolton; iii) length of the hairs of the
      dorsal of the head are equal to the diameter of eye; iv) the length of the hairs
      on the scape and tibiae less than the width of the appendage where they are
      located. This is the second species of the tortuosum group of Tetramorium found
      in the State of Puebla, and the fourth recorded in Mexico.

PMID- 21952962
TI  - Changes in the fat body during the post-embryonic development of the predator
      Toxorhynchites theobaldi (Dyar & Knab) (Diptera: Culicidae).
AB  - Several studies have focused on understanding the biochemistry and morphology of
      the fat body of the hematophagous mosquito Aedes aegypti (L.) (Diptera:
      Culicidae). In contrast, few studies, if any, have focused on morphological
      characters of the fat body in other mosquitoes, especially non-hematophagous taxa
      such as the culicid Toxorhynchites. Larvae of Toxorhynchites prey upon the larvae
      of other mosquito species and are used in vector mosquito control. We
      investigated aspects of the fat body trophocytes, including the morphometric
      analyses of the lipid droplets, protein granules and nuclei, during
      Toxorhynchites theobaldi (Dyar & Knab) post-embryonic development. Following the
      body weight increase from larval stage L2 to L4, the size of lipid droplets
      within the trophocytes also increase, and are likely the result of lipogenesis.
      Lipid droplets decrease in size during L4 to the female pupal stage and increase
      once again during the period from newly-emerged to mature adult females. Protein
      granules are observed for the first time in female pupae, and their appearance
      might be related to protein storage during metamorphosis. The size of the nucleus
      of trophocytes also increases during larval development, followed by a decrease
      during metamorphosis and an additional increase as adult female ages. In
      conclusion, the morphology of the fat body of T. theobaldi changes according to
      the developmental stage. Our study provides for the first time important insights
      into T. theobaldi fat body development and contributes to understand this species
      biology.

PMID- 21952963
TI  - Allometry and ontogeny in Callibia diana Stal (Mantodea: Acanthopidae).
AB  - The life-cycle of Callibia diana Stal is described and linear and geometric
      morphometrics are used for studying allometrics and shape changes throughout this
      neotropical mantid species' life-cycle. Significant changes were expected in the
      allometry and shape of the raptorial leg and abdomen, given the importance of
      hunting and reproduction. The allometric slopes were obtained by using total
      length as the independent variable. Geometric morphometrics of landmarks were
      used for frontal femur and tibia. Hunting and reproduction-related structures had
      the steepest slopes and positive allometries. Negative growth of both disc width
      and head width found in the last moulting event may be a consequence of
      prothoracic muscle growth which is responsible for predatory strike strength. The
      tibial claw and femur of the raptorial leg become larger, while their spines
      become more orthogonal to the longitudinal axes which may facilitate prey
      retention. These changes in mantid shape throughout ontogeny were consistent and
      suggested the resource allocation and development programming of the body that
      improved reaching distance and prey retention.

PMID- 21952964
TI  - Cage and field assessments of Beauveria bassiana-based Mycoinsecticides for Myzus
      persicae Sulzer (Hemiptera: Aphididae) control in cabbage.
AB  - The efficiency of formulated Beauveria bassiana-based mycoinsecticides to control
      Myzus persicae (Sulzer) in cabbage was assessed under field conditions. Aqueous
      conidial suspensions (0.01% Tween 80 + 0.01% v/v Agral) of three fungal isolates
      were sprayed twice at different dates, each with 2.0 x 10(9) viable conidia per
      potted plant using screened cages. The number of nymphs and adults of M. persicae
      per leaf was significantly reduced in plots treated with isolates CG 864 and PL
      63, with control efficiency ranging from 57% to 60%. Further field trials using
      screened cages with isolate CG 864 formulated as oil dispersion reduced the aphid
      population by 85-87% as compared to the control, whereas a 71% reduction was seen
      in plants treated with the aqueous conidial suspension 20 days following the
      first spray. The last experiment was conducted in a commercial cabbage field
      (without cages), in which the fungus was applied at three different dates, each
      with an equivalent of 1.0 x 10(13) viable conidia/ha. The reduction in the number
      of aphids per leaf was more evident between four and five weeks following the
      first spray, resulting in 76-83% and 57-65% control efficiency for oil
      dispersions and unformulated conidia, respectively. However, with the exception
      of imidacloprid-treated plants, rapid aphid re-infestation was observed in all
      treatments. In this study, the stand-alone use of mycoinsecticides for aphid
      control was not a satisfactory strategy, although utilization of B. bassiana in
      IPM strategies remains a field to be explored.

PMID- 21952965
TI  - Host quality of different aphid species for rearing Diaeretiella rapae (McIntosh)
      (Hymenoptera: Braconidae).
AB  - This study aimed to evaluate the quality of the aphid Myzus persicae (Sulzer),
      Lipaphis erysimi (Kaltenbach) and Brevicoryne brassicae (L.) as hosts for the
      parasitoid Diaeretiella rapae (McIntosh). Parasitization by D. rapae was higher
      on M. persicae than on L. erysimi and B. brassicae. The time of development of D.
      rapae from egg to mummy or egg to adult male or female were shorter on M.
      persicae than on L. erysimi and B. brassicae. Moreover, D. rapae showed no
      significant differences in the emergence rate, sex ratio and longevity when
      reared on the three aphid species. Myzus persicae was the largest aphid host,
      with B. brassicae and L. erysimi being of intermediate and of small size,
      respectively. Diaeretiella rapae reared on M. persicae was larger than when
      reared on L. erysimi and B. brassicae, and females of D. rapae were significantly
      larger than males on M. persicae, but males of D. rapae were larger than females
      when reared on L. erysimi. No difference in size was detected between males and
      females in parasitoids reared on B. brassicae. Among the aphid species studied,
      M. persicae was found to be the most suitable to D. rapae.

PMID- 21952966
TI  - [Economic damage level for leaf-cutting ants in function of the productivity
      index of eucalyptus plantations in an Atlantic Forest region].
AB  - The production and quality of eucalyptus plantations have been studied in areas
      with different densities of ant nests, being important to estimate losses caused
      by leaf-cutting ants. The effects of leaf-cutting ant on wood production in
      differents productivity sites were studied in eucalyptus plantations in the
      region of Atlantic Forest, Minas Gerais State, Brazil from 2003 to 2006. Data of
      plots of the continuous forest inventory and data of leaf-cutting ant monitoring
      in eucalyptus plantations were obtained. Each unitary increment in the area of
      Atta spp. nests per hectare reduced the wood production of the eucalyptus forest
      between 0.04 and 0.13 m3.ha(-1), resulting in a level of economic damage for leaf
      cutting ants between 13.4 and 39.2 m2.ha(-1), in this region. Moreover, this
      study innovated when using indices of forest productivity (site index) that
      promote better adjustment of the models and produce estimate more accurate of the
      level of economic damage for leaf-cutting ants in cultivated forests, allowing to
      conclude that the increase of the total area of ant nests reduces the wooden
      volume of eucalyptus, proportionally to the productive potential of the forest.

PMID- 21952967
TI  - Resistance of citrus genotypes to Phyllocnitis citrella Stainton (Lepidoptera:
      Gracillariidae).
AB  - The development and reproduction of the citrus leafminer (CLM), Phyllocnistis
      citrella Stainton, were evaluated in six citrus genotypes in order to identify
      genotypes with resistance traits that could be applied in a program for the
      development of citrus varieties resistant to the citrus leafminer. Tests were
      conducted under controlled laboratory conditions (25 +/- 1oC, 70 +/- 10% RH, and
      14h photophase). Seedlings of each genotype tested were infested with eggs
      obtained from a stock colony of CLM maintained on 'Cravo' lemon (Citrus limonia
      L. Osbeck), and the duration and survival of the eggs, larval and pupal stages,
      pupal size and weight, fecundity and longevity of adults, and sex ratio were
      evaluated. No influence was observed on the duration and survival of eggs, larvae
      and pupae of P. citrella. However, pupae obtained in the hybrid C x R(4) were
      significantly smaller and lighter than pupae from the remaining treatments. Adult
      females from the hybrids C x R(4) and C x R(315) were the least fecund. However,
      the lowest value for the corrected reproductive potential (CRP) was recorded in
      the hybrid C x R(315), suggesting that this genotype is the least favorable for
      the development and reproduction of CLM. On the other hand, the highest CRP value
      obtained in the 'Rugoso' lemon confirms the susceptibility of this genotype,
      indicating it as the most suitable for CLM.

PMID- 21952968
TI  - Silicon influence on resistance induction against Bemisia tabaci biotype B
      (Genn.) (Hemiptera: Aleyrodidae) and on vegetative development in two soybean
      cultivars.
AB  - The potential of populations of Bemisia tabaci (Genn.) to become resistant to
      insecticides has stimulated research into alternative tactics of integrated pest
      management such as the induction of host-plant resistance. Recent data have shown
      that silicon can increase the degree of resistance of host plants to insect
      pests. Therefore the aim of our work was to study the effects of silicon
      application on the vegetative development of soybean plants and on the induction
      of resistance to the silverleaf whitefly, B. tabaci biotype B. We performed
      choice and no-choice tests of oviposition preference on two soybean cultivars,
      IAC-19 (moderately resistant to B. tabaci biotype B) and MONSOY-8001
      (susceptible), with and without application of silicon. Silicon did not affect
      silverleaf whitefly oviposition preferences, but caused significant mortality in
      nymphs. Thus, silicon increased the degree of resistance to silverleaf whitefly.
      Silicon decreased the production of phenolic compounds, but did not affect lignin
      production. However, when applied to cultivar IAC-19, it increased the production
      of non-protein organic nitrogen. Silicon had no effect on the vegetative
      development of soybean plants, but it increased the degree of resistance to the
      silverleaf whitefly. We conclude that silicon applications combined with cultivar
      IAC-19 can significantly decrease silverleaf whitefly populations, having a
      positive impact both on the soybean plant and on the environment.

PMID- 21952969
TI  - Genetic differentiation in natural populations of Lutzomyia longipalpis (Lutz &
      Neiva) (Diptera: Psychodidae) with different phenotypic spot patterns on tergites
      in males.
AB  - Entomological surveys in the state of Maranhao have recorded morphologically
      distinct populations of Lutzomyia longipalpis (Lutz & Neiva). Some populations
      have one pair of spots (1S) on the fourth tergite, while others have two pairs
      (2S) on the third and fourth tergites of males. In the present study we
      investigated the degree of genetic polymorphism among four populations in the
      municipalities of Caxias, Codo and Raposa, in the state of Maranhao, Brazil, by
      using RAPD (Random Amplified Polymorphic DNA) markers. A total of 35 loci were
      identified, of which 30 were polymorphic. The highest polymorphism was observed
      with primer OPA 4, which produced 11 different profiles. Genetic diversity was
      assessed using grouping methods that produced a dendrogram in which the genotypes
      could be clearly separated into two main clades according to the number of spots
      on the male abdominal tergites. One cluster contained the populations from Caxias
      and Codo, and the other was formed by the populations from Raposa and Codo. The
      results of our RAPD analysis showed a clear separation between the populations
      with one and two pairs of spots. The epidemiologic significance of this genetic
      differentiation should be investigated in future studies.

PMID- 21952970
TI  - Nasal mites (Gamasida: Rhinonyssidae) of Paroaria coronata (Miller)
      (Passeriformes: Emberezidae).
AB  - With the aim of identifying the species of nasal mites of Paroaria coronata (red
      crested cardinal), the nasal cavity of 40 birds were examined. The nasal mites
      were identified as Ptilonyssus sairae de Castro and Sternostoma pirangae Pence,
      with 50% and 7.5% of prevalence, respectively. This is the first record of these
      mite species parasitizing P. coronata. This report also amplifies the area of
      occurrence of S. pirangae for Brazil and that of P. sairae for Rio Grande do Sul,
      Brazil.

PMID- 21952971
TI  - Amblyomma dissimile Koch (Acari: Ixodidae) attacking Primolius maracana Vieillot
      (Psittaciformes: Psittacidae) in the Amazon region, State of Para, Brazil.
AB  - The tick Amblyomma dissimile Koch feeds preferentially on reptiles (Squamata),
      although amphibians (Anura) also seem to be important hosts. We report an A.
      dissimile nymph infesting a blue-winged macaw, Primolius maracana, held in
      captivity in the Mangal das Garcas Park, State of Para, Brazil. Environmental
      observations suggest that free-living iguanas (Iguana iguana), which used to walk
      on the bird enclosure in the park, were the source of the A. dissimile tick that
      infested the blue-winged macaw. We provide the second world record of a bird host
      for A. dissimile, and the first bird record for this species in South America.

PMID- 21952972
TI  - New host plant records for Oenomaus ortygnus (Cramer) (Lepidoptera: Lycaenidae)
      in Mexico.
AB  - This is the first record of Oenomaus ortygnus (Cramer) damaging fruits of ilama
      (Annona diversifolia) and extends the butterfly distribution for three states in
      Mexico.

PMID- 21952973
TI  - First report of Elasmus polistis Burks (Hymenoptera: Eulophidae) recovered from
      Polistes versicolor (Olivier) (Hymenoptera: Vespidae) nests in Brazil.
AB  - The first record of Elasmus polistis Burks in Polistes versicolor (Olivier) nests
      in the Rio Grande do Sul state and in Brazil is provided. A total of 173
      specimens of P. versicolor and 790 specimens of E. polistis were collected from
      two nests from Gramado and Santa Cruz do Sul, RS, Brazil.

PMID- 21952974
TI  - First record of Anastrepha flavipennis Greene (Diptera: Tephritidae) and of its
      host in the Brazilian Amazon.
AB  - Anastrepha flavipennis Greene was obtained from Pouteria glomerata (Sapotaceae)
      fruits, known as "abiurana-da-varzea" in the Brazilian Amazon. This is the first
      record of A. flavipennis for the state of Amazonas and of P. glomerata as a host
      for this fruit fly in the Amazon Basin.

PMID- 21952975
TI  - What is the ability of anti-cyclic citrullinated peptide antibodies determination
      in synovial fluid in discriminating rheumatoid arthritis from non-rheumatoid
      arthritis patients? A Tunisian cross-sectional study.
AB  - Anti-cyclic citrullinated peptide antibodies (ACPA) seem to be produced locally
      at the site of joints inflammation in the first stage of rheumatoid arthritis
      (RA). A strong correlation between serum ACPA and ACPA in the synovial fluid (SF
      ACPA) is now suggested. A case-control study was conducted to evaluate the
      usefulness of ACPA determination in SF of patients with RA. A total of 53
      patients with a knee-joint effusion (26 RA, 18 peripheral spondyloarthropathies
      (SPA), and 9 osteoarthritis (OA)) were included in our study. SF samples were
      obtained by performing therapeutic arthrosynthesis. IgG serum ACPA and SF-ACPA
      levels were determined by the enzyme-linked immunosorbent assay (ELISA). We have
      also determined IgG levels in serum and SF by nephelometry. Higher levels of IgG
      ACPA antibodies in SF (p = 0.045) and serum (p = 0.045) were found in patients
      with RA with respect to SPA and OA patients. The Spearman correlation analysis
      showed a significant and positive correlation between ACPA in serum and SF (rho =
      0.516; p = 0.007) not only in the RA group but also in patients with SPA. Serum
      ACPA discriminated RA from non-RA at a cut-off value of 2.7 U/ml (sensitivity,
      69%; specificity, 78%; and area under the curve (AUC), 0.72), whereas SF-ACPA
      discriminated RA from non-RA at a higher cut-off value of 4.95 U/ml (sensitivity,
      73%; specificity, 61%; and AUC, 0.71). Our study suggests that the determination
      of SF-ACPA give complement information to serum ACPA in patients with RA.

PMID- 21952976
TI  - alpha-L-rhamnosidase and beta-D-glucosidase activities in fungal strains isolated
      from alkaline soils and their potential in naringin hydrolysis.
AB  - alpha-L-Rhamnosidases (EC 3.2.1.40) and beta-D-glucosidases (EC 3.2.1.21)
      obtained from several microbial sources are potential catalysts in food,
      beverage, and pharmaceutical industries. However, the enzyme preparations
      currently used have limitations related to the stability and activity of the
      enzyme as well to their reuse. A microtiter screening was carried out in 55
      fungal strains isolated from alkaline soils, to obtain active alpha-L
      rhamnosidases and beta-D-glucosidases at pH 9.0. While alpha-L-rhamnosidase
      activity was detected in 45% of the strains tested, beta-D-glucosidase activity
      was found only in 27%. Based on the fungal ability to produce alpha -L
      rhamnosidase activity, cultures were supplemented with naringin to study the
      activities of the enzymes and the potential of the fungal strains on naringin
      hydrolysis. About 70% of the fungal strains tested increased the activities of
      both enzymes in the naringin-supplemented cultures as compared to non
      supplemented ones. This effect was higher in Acrostalagmus luteo-albus LPSC 427
      (15.3 fold) for alpha-L-rhamnosidase activity and Metarrhizium anisopliae LPSC
      996 (51.1 fold) for beta-D-glucosidase activity. All the enzyme preparations
      tested hydrolyzed naringin at pH 9.0, being that obtained from Acremonium murorun
      LPSC 927 cultures the one which showed highest hydrolysis. Here, different fungal
      species are reported for the first time for their ability to produce alpha-L
      rhamnosidase and beta-D-glucosidase activity at alkaline pH.

PMID- 21952977
TI  - Electronic structure and low temperature thermoelectric properties of In24M8O48
      (M = Ge(4+), Sn(4+), Ti(4+), and Zr(4+)).
AB  - The electronic structure and transport properties of In24M8O48 (M = Ge(4+),
      Sn(4+), Ti(4+), and Zr(4+)) have been studied by using the full-potential
      linearized augmented plane-wave method and the semiclassical Boltzmann theory,
      respectively. It is found that the magnitude of powerfactor with respect to
      relation time follows the order of In24Sn8O48 > In24Zr8O48 > In24Ge8O48 >
      In24Ti8O48. The largest powerfactor is 2.7 * 1012 W/K2 ms for In24Sn8O48 at 60 K,
      which is nearly thirty times larger than those of conventional n-type
      thermoelectric materials. The origin of the different thermoelectric behavior for
      these compounds is discussed from the electronic structure level. It is found
      that, at low temperature, the dopant strongly affect the bands near the Fermi
      level, which consequently leads to their different thermoelectric properties. The
      electronic configuration and the difference in atomic number between the dopant
      and the host atom also play an important role on the thermoelectric properties of
      In24M8O48. Our calculations give a valuable insight on how to enhance the
      thermoelectric performance of In32O48.

PMID- 21952978
TI  - Phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550)
      or adalimumab monotherapy versus placebo in patients with active rheumatoid
      arthritis with an inadequate response to disease-modifying antirheumatic drugs.
AB  - OBJECTIVE: To compare the efficacy, safety, and tolerability of 5 doses of oral
      tofacitinib (CP-690,550) or adalimumab monotherapy with placebo for the treatment
      of active rheumatoid arthritis (RA) in patients with an inadequate response to
      disease-modifying antirheumatic drugs. METHODS: In this 24-week, double-blind,
      phase IIb study, patients with RA (n = 384) were randomized to receive placebo,
      tofacitinib at 1, 3, 5, 10, or 15 mg administered orally twice a day, or
      adalimumab at 40 mg injected subcutaneously every 2 weeks (total of 6 injections)
      followed by oral tofacitinib at 5 mg twice a day for 12 weeks. The primary end
      point was the responder rate according to the American College of Rheumatology
      20% improvement criteria (ACR20) at week 12. RESULTS: Treatment with tofacitinib
      at a dose of >=3 mg twice a day resulted in a rapid response with significant
      efficacy when compared to placebo, as indicated by the primary end point (ACR20
      response at week 12), achieved in 39.2% (3 mg; P <= 0.05), 59.2% (5 mg; P <
      0.0001), 70.5% (10 mg; P < 0.0001), and 71.9% (15 mg; P < 0.0001) in the
      tofacitinib group and 35.9% of patients in the adalimumab group (P = 0.105),
      compared with 22.0% of patients receiving placebo. Improvements were sustained at
      week 24, according to the ACR20, ACR50, and ACR70 response rates as well as
      classifications of remission according to the 3-variable Disease Activity Score
      in 28 joints (DAS28) using C-reactive protein and the 4-variable DAS28 using the
      erythrocyte sedimentation rate. The most common treatment-emergent adverse events
      (AEs) in patients across all tofacitinib treatment arms (n = 272) were urinary
      tract infection (7.7%), diarrhea (4.8%), headache (4.8%), and bronchitis (4.8%).
      CONCLUSION: Tofacitinib monotherapy at >=3 mg twice a day was efficacious in the
      treatment of patients with active RA over 24 weeks and demonstrated a manageable
      safety profile.

PMID- 21952979
TI  - Transcriptome analysis.
AB  - Transcriptome analysis technologies are important systems-biology methods for the
      investigation and optimization of mammalian cell cultures concerning with regard
      to growth rates and productivity. For the production of recombinant proteins,
      knowledge of the expression conditions of the influencing genes is a major issue
      in the improvement of cell lines by means of genome engineering. This chapter
      presents two main techniques for transcriptome analysis: microarray technology
      and next-generation sequencing. Protein-based methods are also briefly outlined.
      Furthermore, the impact of these technologies on mammalian cell culture
      improvement is discussed.

PMID- 21952980
TI  - Chin force in violin playing.
AB  - Force generated between the left mandible of violinists and the chinrest of the
      violin was examined using a force-sensing chinrest developed in this study. A
      strain-gauge force sensor was built, and it was fixed between the violin's top
      plate and a chin cup. Fifteen professional/amateur violinists held the violin
      statically, played musical scales with different sound properties and sounding
      techniques, as well as an excerpt from a Max Bruch concerto. Peak and mean forces
      were evaluated for each task. In a separate experiment, lateral movement of the
      lower teeth due to different levels of voluntary chin force exertion was
      measured. Static holding forces observed were 15 and 22 N with and without the
      help of the left hand, respectively. Peak force increased from 16 N at soft
      dynamics to 20 N at strong dynamics during scales. The force further increased to
      29 N with the use of vibrato technique and 35 N during shifts. Tempo and hand
      position did not affect the force. Playing a Bruch concerto induced a mean peak
      force of 52 N, ranging from 31 to 82 N among the violinists. The developed force
      sensing chinrest could accurately record the generated chin force. Typical chin
      force to stabilize the violin during ordinary musical performance was less than
      30 N, but it could momentarily exceed 50 N when technically demanding musical
      pieces were performed. The lateral shift of the mandible was fairly small (<0.4
      mm) even with high chin-force exertion, possibly due to clenching of the molars.

PMID- 21952981
TI  - Reliability of near infrared spectroscopy (NIRS) for measuring forearm
      oxygenation during incremental handgrip exercise.
AB  - The purpose of this study was to test the reliability of a new handgrip exercise
      protocol measuring forearm oxygenation in 20 healthy subjects on two occasions.
      The retest took place 48 h later and at the same time of the day. The incremental
      exercise consisted of 2 min steps of cyclic handgrip contraction (1/2 Hz)
      separated by 1 min of recovery. The exercise started at 20% MVC, was increased
      with 10% MVC each step and was performed until exhaustion (69.5 and 73% MVC).
      Near infrared spectroscopy (NIRS) was used to measure deoxygenation (deoxy[Hb +
      Mb]) and oxygen saturation (SmO(2)) in the forearm muscles. Prior to the exercise
      protocol an arterial occlusion of the forearm was performed until deoxy(Hb + Mb)
      did no longer increase. Maximal increase in deoxy[Hb + Mb] during 10 s of each
      exercise bout was expressed relative to the occlusion amplitude. ICC was used to
      examine the test-retest reliability. Significant ICC's were reported at 50% (r =
      0.466, p = 0.017) and 60% MVC (r = 0.553, p = 0.005). The group mean of the
      maximum increase in oxygen extraction was 45.6 +/- 16.7% and at the retest 44.9
      +/- 17.0% with an ICC of r = 0.867 (p < 0.001) which could be classified (Landis
      and Koch 1979) as almost perfect. The absolute SmO(2) values showed reliable
      ICC's for every submaximal intensity except at 60% MVC. An ICC of r = 0.774 (p <
      0.001) was found at maximal intensity. The results of the present study show that
      deoxy[Hb + Mb] and SmO(2) responses during this protocol are highly reliable and
      indicate that this protocol could be used to get insight into deoxygenation and
      oxygen saturation in a population with low exercise tolerance.

PMID- 21952982
TI  - Brain temperature measurement: A study of in vitro accuracy and stability of
      smart catheter temperature sensors.
AB  - The injured brain is vulnerable to increases in temperature after severe head
      injury. Therefore, accurate and reliable measurement of brain temperature is
      important to optimize patient outcome. In this work, we have fabricated,
      optimized and characterized temperature sensors for use with a micromachined
      smart catheter for multimodal intracranial monitoring. Developed temperature
      sensors have resistance of 100.79 +/- 1.19Omega and sensitivity of 67.95 mV/
      degrees C in the operating range from15-50 degrees C, and time constant of 180
      ms. Under the optimized excitation current of 500 MUA, adequate signal-to-noise
      ratio was achieved without causing self-heating, and changes in immersion depth
      did not introduce clinically significant errors of measurements (<0.01 degrees
      C). We evaluated the accuracy and long-term drift (5 days) of twenty temperature
      sensors in comparison to two types of commercial temperature probes (USB
      Reference Thermometer, NIST-traceable bulk probe with 0.05 degrees C accuracy;
      and IT-21, type T type clinical microprobe with guaranteed 0.1 degrees C
      accuracy) under controlled laboratory conditions. These in vitro experimental
      data showed that the temperature measurement performance of our sensors was
      accurate and reliable over the course of 5 days. The smart catheter temperature
      sensors provided accuracy and long-term stability comparable to those of
      commercial tissue-implantable microprobes, and therefore provide a means for
      temperature measurement in a microfabricated, multimodal cerebral monitoring
      device.

PMID- 21952984
TI  - Evidence for a role of microRNA-146a in the pathogenesis of systemic lupus
      erythematosus with atherosclerosis: comment on the article by Li et al.

PMID- 21952983
TI  - Comparison of the effects of genetic and environmental risk factors on in situ
      and invasive ductal breast cancer.
AB  - Little is known about the etiology of in situ ductal breast cancer (DCIS) or what
      influences its possible progression to invasive ductal disease. Comparison of
      risk factors for DCIS and invasive ductal cancer may throw some light on these
      issues. We estimated relative risks for DCIS and invasive ductal breast cancer
      according to 12 genetic and eight environmental risk factors among 1.1 million
      postmenopausal women in a large prospective UK study. There was no strong
      evidence of a different association with DCIS versus invasive ductal cancer for
      any of the 12 susceptibility loci examined. We also found similar associations of
      age at menarche, age at first birth, parity, age at menopause, family history of
      breast cancer and use of hormone replacement therapy with DCIS and invasive
      ductal cancer. Only body mass index (BMI) showed a clear difference in
      association in that it was positively associated with the risk of invasive ductal
      cancer but not DCIS (RRs per 5 kg/m(2)  = 1.20 and 1.01, respectively; p-value
      for heterogeneity = 0.002). The very similar risk factor profiles observed here
      for DCIS and invasive ductal cancer suggest that DCIS is a precursor of invasive
      ductal cancer and most risk factors affect the risk of invasive ductal cancer
      primarily through their effects on the risk of DCIS. The lack of association
      between BMI and DCIS suggests a greater influence of BMI on disease progression.

PMID- 21952985
TI  - Prenatal diagnosis of diastematomyelia: a case report and review of the
      literature.
AB  - Diastematomyelia is a rare congenital disorder in which the spinal cord is
      divided longitudinally for part of its length. It can be accurately identified in
      the prenatal period by detailed sonographic examination of the spine. We report a
      case of diastematomyelia localized to spinal levels T6-T9 diagnosed prenatally at
      31 weeks' gestation and review the existing literature on the diagnosis and
      management of this condition during pregnancy.

PMID- 21952986
TI  - Brief communication: comparing loading scenarios in lower first molar supporting
      bone structure using 3D finite element analysis.
AB  - Finite element analysis (FEA) is a widespread technique to evaluate the
      stress/strain distributions in teeth or dental supporting tissues. However, in
      most studies occlusal forces are usually simplified using a single vector (i.e.,
      point load) either parallel to the long tooth axis or oblique to this axis. In
      this pilot study we show how lower first molar occlusal information can be used
      to investigate the stress distribution with 3D FEA in the supporting bone
      structure. The LM(1)  and the LP(2) -LM(1)  of a dried modern human skull were
      scanned by MUCT in maximum intercuspation contact. A kinematic analysis of the
      surface contacts between LM(1)  and LP(2) -LM(1)  during the power stroke was
      carried out in the occlusal fingerprint analyzer (OFA) software to visualize
      contact areas during maximum intercuspation contact. This information was used
      for setting the occlusal molar loading to evaluate the stress distribution in the
      supporting bone structure using FEA. The output was compared to that obtained
      when a point force parallel to the long axis of the tooth was loaded in the
      occlusal basin. For the point load case, our results indicate that the buccal and
      lingual cortical plates do not experience notable stresses. However, when the
      occlusal contact areas are considered, the disto-lingual superior third of the
      mandible experiences high tensile stresses, while the medio-lingual cortical bone
      is subjected to high compressive stresses. Developing a more realistic loading
      scenario leads to better models to understand the relationship between
      masticatory function and mandibular shape and structures. Am J Phys Anthropol,
      2012. (c) 2011 Wiley Periodicals, Inc.

PMID- 21952988
TI  - Sequential learning and rule abstraction in Bengalese finches.
AB  - The Bengalese finch (Lonchura striata var. domestica) is a species of songbird.
      Males sing courtship songs with complex note-to-note transition rules, while
      females discriminate these songs when choosing their mate. The present study uses
      serial reaction time (RT) to examine the characteristics of the Bengalese
      finches' sequential behaviours beyond song production. The birds were trained to
      produce the sequence with an "A-B-A" structure. After the RT to each key position
      was determined to be stable, we tested the acquisition of the trained sequential
      response by presenting novel and random three-term sequences (random test). We
      also examined whether they could abstract the embedded rule in the trained
      sequence and apply it to the novel test sequence (abstract test). Additionally,
      we examined rule abstraction through example training by increasing the number of
      examples in baseline training from 1 to 5. When considered as (gender) groups,
      training with 5 examples resulted in no statistically significant differences in
      the abstract tests, while statistically significant differences were observed in
      the random tests, suggesting that the male birds learned the trained sequences
      and transferred the abstract structure they had learned during the training
      trials. Individual data indicated that males, as opposed to females, were likely
      to learn the motor pattern of the sequence. The results are consistent with
      observations that males learn to produce songs with complex sequential rules,
      whereas females do not.

PMID- 21952989
TI  - "Normal" liver stiffness measure (LSM) values are higher in both lean and obese
      individuals: a population-based study from a developing country.
AB  - The liver stiffness measure (LSM) needs to be explored in ethnically and
      anthropometrically diverse healthy subjects (to derive an acceptable normal
      range) and also in patients with liver disease. In view of this objective, LSM
      was performed by transient elastography (TE) using FibroScan in 437 healthy
      subjects with normal alanine aminotransferase (ALT) levels, recruited from a free
      living population of the Birbhum Population Project (BIRPOP; www.shds.in), a
      Health and Demographic Surveillance System (HDSS), and from 274 patients with
      liver disease attending the Hepatology Clinic of the School of Digestive and
      Liver Diseases (SDLD; Institute of Post Graduate Medical Education & Research
      [IPGME&R], Kolkata, India) including 188 with nonalcoholic fatty liver disease
      (NAFLD) and 86 with chronic hepatitis of viral and other etiologies. Liver biopsy
      was performed in 125 patients. The range of normal values for LSM, defined by 5th
      and 95th percentile values in healthy subjects, was 3.2 and 8.5 kPa,
      respectively. Healthy subjects with a lower body mass index (BMI; < <18.5
      kg/m(2)) had a higher LSM compared with subjects who had a normal BMI; this LSM
      value was comparable to that of obese subjects (6.05 +/- 1.78 versus 5.51 +/-
      1.59 and 6.60 +/- 1.21, P = 0.016 and 0.349, respectively). Liver disease
      patients without histologic fibrosis had significantly higher LSM values compared
      with healthy subjects (7.52 +/- 5.49 versus 5.63 +/- 1.64, P < 0.001). Among the
      histologic variables, stage of fibrosis was the only predictor for LSM. LSM did
      not correlate with inflammatory activity and ALT in both NAFLD and chronic
      hepatitis groups. CONCLUSION: LSM varies between 3.2 and 8.5 kPa in healthy
      subjects of South Asian origin. Both lean and obese healthy subjects have higher
      LSM values compared with subjects with normal BMI. Liver stiffness begins to
      increase even before fibrosis appears in patients with liver disease.

PMID- 21952987
TI  - NADPH oxidase inhibition ameliorates Trypanosoma cruzi-induced myocarditis during
      Chagas disease.
AB  - Trypanosoma cruzi, the aetiological agent of Chagas disease, invades nucleated
      mammalian cells including macrophages. In this study, we investigated the
      crosstalk between T. cruzi-induced immune activation of reactive oxygen species
      (ROS) and pro-inflammatory responses, and their role in myocardial pathology.
      Splenocytes of infected mice (C3H/HeN) responded to Tc-antigenic stimulus by more
      than a two-fold increase in NADPH oxidase (NOX) activity, ROS generation,
      cytokine production (IFN-gamma > IL-4 > TNFalpha > IL1-beta~ IL6), and
      predominant expansion of CD4(+) and CD8(+) T cells. Inhibition of NOX, but not of
      myeloperoxidase and xanthine oxidase, controlled the ROS (>98%) and cytokine (70
      89%) release by Tc-stimulated splenocytes of infected mice. Treatment of infected
      mice with apocynin (NOX inhibitor) in drinking water resulted in a 50-90% decline
      in endogenous NOX/ROS and cytokine levels, and splenic phagocytes' proliferation.
      The splenic percentage of T cells was maintained, though more than a 40% decline
      in splenic index (spleen weight/body weight) indicated decreased T-cell
      proliferation in apocynin-treated/infected mice. The blood and tissue parasite
      burden were significantly increased in apocynin-treated/infected mice, yet acute
      myocarditis, ie inflammatory infiltrate consisting of macrophages, neutrophils,
      and CD8(+) T cells, and tissue oxidative adducts (eg 8-isoprostanes, 3
      nitrotyrosine, and 4-hydroxynonenal) were diminished in apocynin-treated/infected
      mice. Consequently, hypertrophy (increased cardiomyocytes' size and beta-MHC,
      BNP, and ANP mRNA levels) and fibrosis (increased collagen, glycosaminoglycans,
      and lipid contents) of the heart during the chronic phase were controlled in
      apocynin-treated mice. We conclude that NOX/ROS is a critical regulator of the
      splenic response (phagocytes, T cells, and cytokines) to T. cruzi infection, and
      bystander effects of heart-infiltrating phagocytes and CD8(+) T cells resulting
      in cardiac remodelling in chagasic mice.

PMID- 21952990
TI  - Muscle metabolic alterations assessed by 31-phosphorus magnetic resonance
      spectroscopy in mild Becker muscular dystrophy.
AB  - Although the molecular defect causing Becker muscular dystrophy (BMD) has been
      identified, the biochemical mechanisms that lead to muscle necrosis remain
      unclear. Exercise-related muscle metabolism in 9 mildly affected BMD patients was
      assessed by muscle 31-phosphorus magnetic resonance spectroscopy ((31)P MRS)
      during an incremental workload. Compared with normal controls, BMD patients
      showed deregulation of resting pH and intramuscular membrane breakdown. We also
      observed increased reliance upon anaerobic metabolism during sustained submaximal
      contraction and maintenance of oxidative function during recovery.

PMID- 21952991
TI  - MutYH mutation carriers have increased breast cancer risk.
AB  - BACKGROUND: Variants of the mutY homolog gene MutYH, a DNA repair gene, are
      associated with increased risk of colorectal cancer; however, it remains unclear
      whether these variants also are associated with the risk of other cancers. The
      authors studied the risk of breast cancer associated with MutYH variants in a
      unique ethnic group of Sephardi Jews in Israel with a high prevalence of MutYH
      mutations. METHODS: The study participants were 930 Sephardi Jewish women of
      North African origin who were recruited into the population-based case-control
      Breast Cancer in Northern Israel Study (BCINIS) either as breast cancer cases or
      as healthy controls. All participants contributed a blood sample and completed an
      interview. Two MutYH variants, a glycine-to-aspartic acid substitution at codon
      396 (G396D) and a tyrosine-to-cysteine substitution at codon 179 (Y179C), were
      studied. RESULTS: In the Sephardi Jews, among the healthy controls, 20 women
      (3.7%) were homozygote or heterozygote carriers of the G396D variant, and 4 women
      (0.7%) were heterozygote carriers of the Y179C variant. Breast cancer cases had a
      6.7% prevalence of G396D, yielding a significantly elevated risk estimate for
      breast cancer (odds ratio, 1.86; 95% confidence interval, 1.02-3.39; P = .039).
      The tumors detected in carriers with MutYH variants were similar in
      characteristics to those without MutYH variants, as was the age at diagnosis.
      CONCLUSIONS: Carriers of variants in MutYH, although not very common, may have an
      increased risk of breast cancer in Jews of North African origin. Identification
      of such carriers and special surveillance protocols may be warranted.

PMID- 21952992
TI  - Primary liver cancer presenting as pyogenic liver abscess: characteristics,
      diagnosis, and management.
AB  - BACKGROUND AND OBJECTIVES: Primary liver cancer (PLC) presenting as pyogenic
      liver abscess (PLA) is potentially life-threatening, but has been occasionally
      reported, especially for cholangiocarcinoma. METHODS: Medical records of nine
      patients who presented as PLA, but were eventually confirmed as hepatocellular
      carcinoma (HCC; n = 5) or intrahepatic cholangiocarcinoma (IHCC; n = 4), from
      September 1997 through April 2011, were retrospectively reviewed. RESULTS:
      Presenting symptoms included fever, chills, right-upper-quadrant abdominal pain,
      nausea, vomiting, weight loss, and diarrhea. Physical signs included tenderness
      in the right-upper-quadrant abdomen, jaundice, and ascites. With the exception of
      elevated alpha-fetoprotein (AFP) in HCC patients and elevated carbohydrate
      antigen 19-9 (CA19-9) in IHCC patients, lab results were not significantly
      different between these nine patients and PLA patients. All the nine patients
      underwent invasive treatment in addition to antibiotics. CONCLUSIONS: Elevated
      AFP and CA19-9 could suggest HCC and IHCC in patients with symptoms/signs typical
      of PLA. Contrast-enhanced computed tomography could be helpful in patients with
      normal AFP and CA19-9. Making an accurate and early diagnosis and seizing the
      opportunity of surgery are essential to improve the management strategies of
      patients with PLC mimicking PLA.

PMID- 21952993
TI  - Lupus clinical trials: medication failure or failure in study design.

PMID- 21952994
TI  - IgA nephropathy in patients with spondyloarthritis followed-up at the
      Rheumatology Service of Hospital das Clinicas/UFMG.
AB  - OBJECTIVE: To determine the frequency of glomerulonephritis in patients with
      spondyloarthritis followed-up at a Brazilian Rheumatology Service, and to
      evaluate the clinical variables associated. PATIENTS AND METHODS: Patients were
      assessed for sociodemographic characteristics, type of spondyloarthritis, time
      since diagnosis and disease activity, non-steroidal anti-inflammatory drug use,
      HLA-B27 positivity, creatinine and urea serum levels, major comorbidities,
      hematuria and proteinuria. Patients with hematuria were subsequently assessed for
      the presence of dysmorphic red blood cells in urine, and those with proteinuria
      underwent 24-hour urine protein measurement. Renal biopsy was performed in
      patients with glomerular hematuria and/or proteinuria over 3.5 g/24-hour.
      RESULTS: Seventy-six patients were assessed. Microscopic hematuria was the most
      frequently found abnormality in urinalysis (44.7%), usually intermittent and in
      spot urine samples during patients' follow-up. In eight patients (10.5%),
      glomerular hematuria was suspected. Renal biopsy was performed in fi ve of them,
      showing IgA nephropathy in four (5.3%) and thin membrane disease in one patient.
      CONCLUSIONS: A high frequency of urinalysis alterations was observed in that
      subgroup of patients, as well as a high prevalence of IgA nephropathy. Although
      further studies on this subject are needed to better clarify these results,
      periodic urinalysis of patients with spondyloarthritis should be recommended.

PMID- 21952995
TI  - Prevalence of clinical and laboratory manifestations and comorbidities in
      polymyositis according to gender.
AB  - OBJECTIVE: To assess gender distribution in polymyositis (PM) and its influence
      on disease, regarding clinical and laboratory manifestations, outcome and
      comorbidities. METHODS: Retrospective single-center cohort study assessing 75
      consecutive patients with PM (Bohan and Peter, 1975) from 1990 to 2010.
      Complementary tests were related to early diagnosis of PM. RESULTS: The study
      assessed 52 women and 23 men (ratio 2.3:1), most of whom white (84.0%), with a
      mean age of 42.7 +/- 13.7 years (16 to 67 years), and mean disease duration of
      6.9 +/- 5.5 years (0 to 20 years). Approximately 50% experienced disease relapse
      during follow-up. Nevertheless, two thirds were in remission at the end of this
      study, with 4.0% of deaths. There was no difference between genders regarding
      demographic, clinical and laboratory characteristics, clinical outcome and the
      drug therapy instituted. Regarding comorbidities, there was a high prevalence of
      hypertension (38.7%) and diabetes mellitus (17.3%), equally distributed between
      genders. There was also a high prevalence of depression and fibromyalgia, which
      were only observed among females. CONCLUSIONS: The prevalence of PM was higher
      among women than among men (2.3:1). Because the prevalence of comorbidities was
      high in the case series studied, it is worth emphasizing the need for their
      control to provide better quality of life for patients with PM.

PMID- 21952996
TI  - Immediate effect of the elastic knee sleeve use on individuals with
      osteoarthritis.
AB  - BACKGROUND: Knee osteoarthritis (KOA) is one of the major reasons for seeking
      medical and physical therapy services, because it usually causes difficulties in
      performing daily life activities. There are several types of treatment, with
      varied results. The use of knee sleeve as an adjuvant resource has been
      controversial in the literature. OBJECTIVE: To assess the immediate efficacy of
      elastic knee sleeve on pain and functional capacity of individuals with KOA.
      METHODS: Seventy-four patients (132 knees) with symptomatic KOA were assessed by
      use of the Stair Climb Power Test (SCPT), Timed Up and Go (TUG) and 8-Meter Walk
      (8MW) tests, in addition to the VAS for pain. The tests were performed with and
      without knee sleeves, with a cover on the knees to hide knee sleeve. The order
      and the presence of the knee sleeve were randomized, and the investigator was
      blind. RESULTS: A statistically significant difference was found between the two
      compared circumstances (with and without knee sleeve) when using the VAS (P <
      0.001), which showed a reduction in pain with the knee sleeve use. Analyses of
      the three functional tests under both circumstances were performed, resulting in
      statistically significant differences in 8MW and TUG tests (P < 0.05), but not in
      SCPT (P > 0.1339). CONCLUSION: The elastic knee sleeve proved to be effective to
      immediately improve the functional capacity and pain of individuals with KOA,
      because it enhanced performance during the tests proposed. Thus, the knee sleeve
      is an adjuvant resource for treating KOA, because it is practical, useful, and of
      easy clinical use, and can aid in the practice of therapeutic exercises.

PMID- 21952997
TI  - Correlation of fatigue with pain and disability in rheumatoid arthritis and
      osteoarthritis, respectively.
AB  - OBJECTIVE: To investigate the correlation of fatigue with pain in rheumatoid
      arthritis patients and with disability in osteoarthritis patients. METHODS:
      Twenty patients with rheumatoid arthritis and 20 patients with osteoarthritis
      were evaluated. The degree of fatigue was evaluated with a visual analogue scale
      and the Multidimensional Assessment of Fatigue. Pain was evaluated with a visual
      analogue scale as well as Patient Global Assessment. For disability evaluation,
      the Health Assessment Questionnaire was performed. Age, gender, disease duration,
      education, income, antirheumatic drugs used and comorbidity were also obtained.
      Statistical analysis included Fisher exact, Shapiro-Wilk, Kruskal-Wallis and
      Spearman tests. The significance level was 0.05. RESULTS: Fatigue was more
      significantly increased in patients with osteoarthritis than in patients with
      rheumatoid arthritis when evaluated with Multidimensional Assessment of Fatigue
      (P < 0.05). Pain was found to correlate with fatigue evaluated with visual
      analogue scale or Multidimensional Assessment of Fatigue in patients with
      rheumatoid arthritis (r = 0.46; P < 0.05). Health Assessment Questionnaire was
      associated with fatigue visual analogue scale in patients with osteoarthritis (r
      = 0.54; P < 0.05). Patient Global Assessment correlates with fatigue visual
      analogue scale (r = 0.44; P < 0.003). Patients were similar in both groups: all
      females, similar mean age, with long disease duration and low income. CONCLUSION:
      Our results corroborate that fatigue in rheumatoid arthritis patients correlates
      with the degree of pain, while in osteoarthritis patients it is associated with
      disability. Therefore, we found that fatigue has different correlates in
      osteoarthritis and rheumatoid arthritis, and we suggest that disability, not
      pain, is a correlate of fatigue in osteoarthritis patients.

PMID- 21952998
TI  - Prolactin, estradiol and anticardiolipin antibodies in premenopausal women with
      systemic lupus erythematosus: a pilot study.
AB  - INTRODUCTION: Systemic lupus erythematosus (SLE) is an autoimmune disease, with
      higher prevalence in women. An incidence peak occurs during the reproductive
      years, suggesting that estradiol may play a role in the clinical presentation of
      SLE. Anticardiolipin antibodies (ACA) are associated with antiphospholipid
      antibody syndrome (APLS), but can be found in patients with SLE without APLS, and
      relate to cardiovascular risk and nephrite. OBJECTIVE: This study aimed at
      assessing whether the presence of ACA is associated with hormonal changes in a
      sample of women with SLE. METHODS: Forty-seven women diagnosed with SLE according
      to the American College of Rheumatology criteria, aged 30.8 +/- 8.12 years, were
      evaluated. None was on hormonal contraception, and their SLE activity was
      estimated using the SLE Disease Activity Index (SLEDAI). Patients were
      stratified, according to the presence or absence of ACA, and estradiol and
      prolactin levels were measured. RESULTS: Nine (19.1%) of 47 patients were
      positive for ACA. No differences were found between groups concerning age,
      duration of disease, and SLEDAI. In contrast, the median estradiol level was
      lower in the ACA-positive group [46.8 (21.0-72.1) pg/mL] than in the ACA-negative
      group [122.3 (64.8-172.7) pg/mL, P = 0.004]. CONCLUSION: These results suggest,
      for the first time, an inverse association between ACA and estradiol levels in
      premenopausal SLE patients. Considering that both lower endogenous estradiol
      levels and ACA positivity are related to atherosclerosis, our finding may be
      clinically relevant in predicting cardiovascular risk and/or APLS development in
      SLE.

PMID- 21952999
TI  - Study of the frequency of HLA-DRB1 alleles in Brazilian patients with rheumatoid
      arthritis.
AB  - The HLA-DRB1 alleles encoding an amino acid sequence (QKRAA/QRRAA/RRRAA) at
      position 70 74 of the third hypervariable region of the beta1 chain of the HLA
      DRB1 gene, called shared epitope (SE), are associated with increased
      susceptibility to and severity of rheumatoid arthritis (RA) in different
      populations. OBJECTIVE: To determine the frequency of HLA-DRB1 alleles in
      Brazilian patients with RA and their association with rheumatoid factor (RF) and
      anti-citrullinated peptide antibodies (ACPA). METHODS: Four hundred and twelve
      patients with RA (ACR 1987) and 215 controls were included. HLA-DRB1 typing was
      performed by use of polymerase chain reaction (PCR) with specific primers and
      hybridization with sequence-specific oligonucleotide probe (SSOP). ACPA was
      measured by use of the ELISA technique and RF by nephelometry. The statistical
      analysis comprised the chi-square and Student t tests and logistic regression.
      RESULTS: HLA-DRB1*04:01, *04:04, *04:05 alleles were associated with RA (P <
      0.05); despite the wide confidence interval, it is worth noting the association
      between the DRB1*09:01 allele and RA (P < 0.05). HLA-DRB1 SE+ alleles were
      observed in 62.8% of the patients and in 31.1% of controls (OR 3.62; P < 0.001)
      and were associated with ACPA (OR 2.03; P < 0.001). DRB1-DERAA alleles showed a
      protective effect against RA (OR 0.42; P < 0.001). CONCLUSION: In a sample of
      Brazilian patients with RA, most of whom of mixed heritage, HLA-DRB1 SE+ alleles
      were associated with susceptibility to disease and presence of ACPA.

PMID- 21953000
TI  - Therapeutic effects of exercise training in patients with pediatric rheumatic
      diseases.
AB  - Over the past decades, the role of exercise training in rheumatic diseases has
      been largely explored. Currently, physical activity is well known to benefit
      patients with osteoporosis, osteoarthritis, systemic lupus erythematosus,
      systemic sclerosis, idiopathic inflammatory myopathy, fibromyalgia and rheumatoid
      arthritis. Therefore, exercise training has been considered a valuable tool for
      treating rheumatic patients. The therapeutic effects of exercise training have
      also been investigated in pediatric rheumatic diseases. Collectively, studies
      have revealed the therapeutic potential of exercise in juvenile idiopathic
      arthritis, juvenile systemic lupus erythematosus, juvenile dermatomyositis,
      juvenile fibromyalgia and other causes of chronic pain. The aim of this review is
      to familiarize the pediatric rheumatologist with the exercise science field;
      discuss the potential benefits of exercise training in pediatric rheumatic
      diseases, emphasize both research and clinical perspectives of this promising
      field; and propose practical models of pre-participation examinations and
      contraindications to exercise.

PMID- 21953001
TI  - Expression of complement regulatory proteins CD55, CD59, CD35, and CD46 in
      rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is an autoimmune disease associated with polyarticular
      inflammatory synovitis affecting mainly peripheral joints. It affects
      approximately 1% of the world population, being two to three times more prevalent
      in women. Rheumatoid arthritis has a complex and multifactorial pathogenesis. The
      synovium of the affected joints is infiltrated by T and B lymphocytes,
      macrophages, and granulocytes. The rheumatoid synovium has proliferative
      characteristics, forming the pannus, which invades cartilage and bone, leading to
      normal architecture destruction and function loss. The decreased expression of
      complement regulatory proteins (CRP) seems to play an important role in RA
      activity, and is associated with worsening of the clinical symptoms. In several
      models of autoimmune diseases, the overactivation of the complement system (CS)
      is the cause of disease exacerbation. This article aimed at reviewing the main
      aspects related to CS regulation in RA in order to provide a better understanding
      of the potential role of this system in the pathophysiology and activity of the
      disease.

PMID- 21953002
TI  - Phlegmasia cerulea dolens in patient with systemic lupus erythematosus in the
      remote postpartum period.
AB  - Vascular manifestations are not rare in systemic lupus erythematosus and, in most
      cases, are associated with antiphospholipid antibodies. Phlegmasia cerulea dolens
      is an unusual and severe complication of deep venous thrombosis of the lower
      limbs, which has a high mortality rate. In the literature, only two cases of
      phlegmasia cerulea dolens associated with primary antiphospholipid syndrome have
      been reported, but none associated with systemic lupus erythematosus. We report
      one case of phlegmasia cerulea dolens with rapid evolution to death in a patient
      with systemic lupus erythematosus in the remote postpartum period.

PMID- 21953003
TI  - Septic arthritis due to Streptococcus bovis in a patient with liver cirrhosis due
      to hepatitis C virus: case report and literature review.
AB  - Monoarthritis remains a diagnostic challenge in Rheumatology and Orthopedics. The
      author reports a case of septic arthritis due to Streptococcus bovis after
      several episodes of joint effusion treated with hyaluronic acid (Hylan G-F 20)
      and methylprednisolone acetate in a 69-year-old patient with liver cirrhosis due
      to hepatitis C virus. Neither adenoma of the colon nor endocarditis was present.
      The diagnostic possibilities for this case of monoarthritis, the pathologies
      related to the microorganism of interest to the rheumatologist, and the possible
      involvement of joint reaction to hyaluronic acid as a predisposing factor to
      joint effusion are discussed.

PMID- 21953004
TI  - Takayasu's arteritis in children and adolescents: report of three cases.
AB  - Takayasu's arteritis (TA) is a systemic vasculitis that affects mainly the aorta
      and its major branches. Despite being the third most frequent vasculitis in
      childhood, the occurrence of TA in the pediatric age group is scarce. We report
      three cases of TA in children, emphasizing signs and symptoms, angiographic
      alterations and therapeutics.

PMID- 21953005
TI  - The presence of the Brazilian rheumatology in the GRAPPA.

PMID- 21953006
TI  - Synthesis of alpha,beta-unsaturated gamma-amino esters with a quaternary center
      by ruthenium-catalyzed codimerization of N-acetyl alpha-arylenamines and
      acrylates.
AB  - Ruthenium-catalyzed highly selective codimerization of N-acetyl alpha
      arylenamines with ethyl acrylates is reported. This codimerization reaction
      provides a new efficient method for the synthesis of alpha,beta-unsaturated gamma
      amino esters with a quaternary center.

PMID- 21953007
TI  - Change in physical activity during active treatment in a prospective study of
      breast cancer survivors.
AB  - Physical activity offers many benefits to breast cancer survivors, yet research
      on physical activity during the immediate period following a breast cancer
      diagnosis is limited. In a prospective cohort study of 1,696 women diagnosed with
      invasive breast cancer in the Kaiser Permanente Northern California Medical Care
      Program from 2006-2009, we describe change in self-reported physical activity
      levels from around diagnosis to 6 months post-diagnosis and determine factors
      associated with change. Participants completed a comprehensive physical activity
      questionnaire at baseline (2 months post-diagnosis) and at follow-up (8 months
      post-diagnosis). Predictors of physical activity change were determined by
      multivariable linear regression. Reductions in all physical activity levels were
      observed (P < 0.0001); mean (SD) change (h/week) of moderate-vigorous physical
      activity (MVPA) was -1.28 (4.48) and sedentary behavior was -0.83 (6.95). In
      fully-adjusted models, overweight and obesity were associated with greater
      declines in MVPA of -1.58 h/week (SD = 0.92) and -1.29 h/week (SD = 0.93),
      respectively (P = 0.0079). Receipt of chemotherapy only was also associated with
      a greater decrease in MVPA (-2.12 h/week; SD = 0.92; P < 0.0001), specifically
      for recreational activities (-1.62 h/week; SD = 0.64; P = 0.0001). These data
      suggest challenges in maintaining physical activity levels during active
      treatment among women with breast cancer. Interventions to encourage physical
      activity in breast cancer survivors should be pursued.

PMID- 21953008
TI  - Prediction of tumour necrosis fractions using metabolic and volumetric 18F-FDG
      PET/CT indices, after one course and at the completion of neoadjuvant
      chemotherapy, in children and young adults with osteosarcoma.
AB  - PURPOSE: The utility of combined metabolic and volumetric (18)F-FDG PET/CT
      indices for predicting tumour necrosis fractions following neoadjuvant
      chemotherapy has not been extensively studied in osteosarcoma. Furthermore,
      little is known of the early PET/CT responses after only one chemotherapy course.
      METHODS: Enrolled in the study were 20 children and young adults with resectable
      osteosarcoma who had undergone (18)F-FDG PET/CT scans before and after
      neoadjuvant chemotherapy. Maximum standardized uptake value (mSUV), metabolic
      tumour volume (MTV), and total lesion glycolysis (TLG) were measured. From among
      the 20 patients, 14 were prospectively recruited and underwent an additional
      PET/CT scan after one chemotherapy course. Histopathological necrosis fractions
      were compared with the above-mentioned PET/CT indices and their ratios. RESULTS:
      MTV at the SUV threshold of 2 g/ml was closely correlated with the magnetic
      resonance image volumes before therapy (r = 0.91). In the prospective cohort,
      five patients were classified as good responders and nine as poor responders. All
      the metabolic indices (mSUV and its ratio) and combined metabolic/volumetric
      indices (MTV, TLG, and their ratios) except the mSUV ratio determined after
      therapy showed significant differences between good and poor responders (P
      <0.05). Differences were also noted for all of these indices determined after one
      chemotherapy course. Furthermore, most of these indices determined after therapy
      as well as after one chemotherapy course had good sensitivity, specificity,
      positive predictive value and negative predictive value with respect to
      predicting histological response to chemotherapy. CONCLUSION: In our osteosarcoma
      patient population, (18)F-FDG PET/CT indices (either combined
      metabolic/volumetric or metabolic indices) determined after neoadjuvant
      chemotherapy were useful in predicting tumour responses. This held true after
      only one chemotherapy course.

PMID- 21953009
TI  - PDGF-AA mediates B104CM-induced oligodendrocyte precursor cell differentiation of
      embryonic neural stem cells through Erk, PI3K, and p38 signaling.
AB  - The conditioned medium from B104 neuroblastoma cells (B104CM) induces neural stem
      cells (NSCs) to differentiate into OPCs in vitro, which indicates that certain
      factor(s) contained within the B104CM must give instructional signals that direct
      OPC differentiation of NSCs. However, the OPC-inductive factor(s) present within
      the B104CM has not been well identified yet. Platelet-derived growth factor AA
      (PDGF-AA) was not only known to be a potent mitogen for OPC proliferation but
      also to act as a regulator of oligodendrocyte differentiation from multipotent
      embryonic NSCs. This raises the possibility that B104CM induces OPC
      differentiation of NSCs through secretion of PDGF-AA. In the present study, we
      detected the expression of PDGF-AA mRNA in B104 cells and the high level of PDGF
      AA protein in B104CM. Most importantly, B104CM-induced OPC differentiation of
      NSCs could be completely blocked by AG1295, a specific inhibitor of PDGFR signal
      pathway, suggesting that the PDGF-AA in B104CM is the key factor that induces
      NSCs to differentiate into OPCs. Moreover, such B104CM-induced OPC
      differentiation appears to be mediated by the extracellular signal-regulated
      kinases 1 and 2 (Erk1/2), phosphatidylinositol-3 kinase (PI3K), and p38 signal
      pathway because B104CM elicited the activation of Erk1/2, PI3K, and p38, which
      could be markedly blocked by U0126, LY294002, and SB203580, several specific
      inhibitors of these signal pathway, respectively. These inhibitors also abolished
      OPC differentiation of NSCs completely. Together our study suggests that PDGF-AA
      contained in B104CM is the key regulating molecule that instructs OPC
      differentiation from embryonic NSCs through the activation of Erk, PI3K, and p38
      signal pathway in vitro.

PMID- 21953010
TI  - Regulation of Na+/H+ exchanger in dendritic cells by Akt2.
AB  - Dendritic cells (DCs) are antigen-presenting cells decisive in primary immune
      responses and establishment of immunological memory. They are activated by
      bacterial lipopolysaccharides (LPS), which lead to activation of Na(+)/H(+)
      exchanger activity, cell swelling, reactive oxygen species (ROS) formation, and
      migration. The effects require functional phosphoinositide 3 kinase and are
      paralleled by Akt phosphorylation. The present study explored the putative
      involvement of the Akt isoform Akt2. To this end, experiments were performed in
      DCs isolated from bone marrow of mice lacking functional Akt2/PKBbeta (akt2 (-/
      )) and respective wild-type animals (akt2 (+/+)). Based on BCECF fluorescence,
      cytosolic pH (pH(i)) was significantly lower in akt2 (-/-) than in akt2 (+/+)
      DCs. Transient exposure to NH(4)Cl was followed by profound cytosolic
      acidification in both genotypes. Subsequent re-alkalinization was largely
      dependent on Na(+) thus reflecting Na(+)/H(+) exchanger activity and was
      significantly lower in akt2 (-/-) than in akt2 (+/+) DCs. According to forward
      scatter in FACS analysis, cell volume was significantly lower in akt2 (-/-) than
      in akt2 (+/+) DCs. Exposure of DCs to LPS led within 4 h to significant increases
      of Na(+)/H(+) exchanger activity, cell volume, ROS production, and migration in
      akt2 (+/+) mice, and its effects were significantly blunted in akt2 (-/-) DCs.
      The present observations disclose a role of Akt2 in the regulation of pH(i), cell
      volume, ROS production, and migration in dendritic cells.

PMID- 21953012
TI  - Tail growth tracks the ontogeny of prehensile tail use in capuchin monkeys (Cebus
      albifrons and C. apella).
AB  - Physical anthropologists have devoted considerable attention to the structure and
      function of the primate prehensile tail. Nevertheless, previous morphological
      studies have concentrated solely on adults, despite behavioral evidence that
      among many primate taxa, including capuchin monkeys, infants and juveniles use
      their prehensile tails during a greater number and greater variety of positional
      behaviors than do adults. In this study, we track caudal vertebral growth in a
      mixed longitudinal sample of white-fronted and brown capuchin monkeys (Cebus
      albifrons and Cebus apella). We hypothesized that young capuchins would have
      relatively robust caudal vertebrae, affording them greater tail strength for more
      frequent tail-suspension behaviors. Our results supported this hypothesis. Caudal
      vertebral bending strength (measured as polar section modulus at midshaft) scaled
      to body mass with negative allometry, while craniocaudal length scaled to body
      mass with positive allometry, indicating that infant and juvenile capuchin
      monkeys are characterized by particularly strong caudal vertebrae for their body
      size. These findings complement previous results showing that long bone strength
      similarly scales with negative ontogenetic allometry in capuchin monkeys and add
      to a growing body of literature documenting the synergy between postcranial
      growth and the changing locomotor demands of maturing animals. Although expanded
      morphometric data on tail growth and behavioral data on locomotor development are
      required, the results of this study suggest that the adult capuchin prehensile
      tail phenotype may be attributable, at least in part, to selection on juvenile
      performance, a possibility that deserves further attention.

PMID- 21953013
TI  - A novel treatment strategy for EGFR mutant NSCLC with T790M-mediated acquired
      resistance.
AB  - The purpose of our study was to identify novel kinase inhibitors for the
      treatment of genetic subsets of non-small cell lung cancer (NSCLC). NSCLC cell
      lines (n = 8) with known oncogenic backgrounds (K-Ras, EGFR and EML4-ALK) were
      exposed to several kinase inhibitors and analyzed for cell growth/cytotoxicity
      and signaling. Go6976, a classical protein kinase C inhibitor, showed high
      potency against mutated EGFR and was further validated in vitro using additional
      NSCLC lines (n = 4) and Ba/F3 models and in vivo using a xenograft model. Go6976
      was identified to be a potent inhibitor of mutated EGFR with IC50 values from
      0.033 nM to 3.3 MUM and down regulating phosphorylation of EGFR, AKT and ERK1/2
      at concentrations in the range of the IC(50)  values. Go6976 has only a minor
      effect on wild-type EGFR and cell lines independent of signaling from the mutant
      EGFR. Most importantly, the activity of Go6976 remains unchanged despite the
      presence of the T790M-mediated resistance, and it prevents the occurrence of this
      resistance in vitro. Go6976 was also shown to significantly reduce tumor growth
      in an in vivo xenograft model with a EGFR-mutated NSCLC cell line containing
      T790M. These findings demonstrate that Go6976 acts as a potent inhibitor of
      mutant EGFR despite the presence of T790M, the most important mechanism of
      acquired resistance for EGFR tyrosine kinase inhibitors, in both in vitro and in
      vivo models.

PMID- 21953011
TI  - Drug-induced sleep: theoretical and practical considerations.
AB  - Faithful replication of normal sleep through medications--can it be achieved?
      Departure from normal sleep with the use of drugs--when is it desired? Answers to
      these questions depend on accurate understanding of sleep and on concrete
      criteria upon which to define it. Since these elements are evolving sciences, as
      yet incompletely known, one might take a nihilistic approach that we simply
      cannot judge whether we have successfully replicated sleep, since we do not fully
      grasp what sleep is or what it does. To address these potential obstacles, our
      article is written in two sections. The first addresses theoretical
      considerations for how medications might be seen in the larger framework of
      sleep. The purpose of this section is to inform readers about key issues in
      evaluating whether a drug has sufficient data to persuasively argue it is re
      creating sleep. (We hope that researchers interested in conducting studies, or
      critical readers of the drug-study literature, might find this section
      particularly useful.) The second section of this article approaches exemplary,
      current concepts of pharmacologic manipulation of sleep, organized by disorders
      as articulated by the International Classification of Sleep Disorders (2005).
      This second section will combine practical knowledge of clinical sleep medicine,
      with emphasis on contemporary knowledge about molecular mechanisms that are felt
      to underlie some of these phenomena. We recognize that our collective knowledge
      about sleep will advance in the coming years. We hope that this article serves to
      facilitate that advance.

PMID- 21953014
TI  - Culture-independent analysis of the soil bacterial assemblage at the Great Salt
      Plains of Oklahoma.
AB  - The Great Salt Plains (GSP) of Oklahoma is a natural inland terrestrial
      hypersaline environment that forms evaporite crusts of mainly NaCl. Previous work
      described GSP bacterial assemblages through the phylogenetic and phenetic
      characterization of 105 isolates from 46 phylotypes. The current report describes
      the same bacterial assemblages through culture-independent 16S rRNA gene clone
      libraries. Although from similar hypersaline mud flats, the bacterial libraries
      from two sites, WP3 and WP6, were quite different. The WP3 library was dominated
      by cyanobacteria, mainly Cyanothece and Euhalothece. The WP6 library was rich in
      anaerobic sulfur-cycle organisms, including abundant Desulfuromonas. This pattern
      likely reflects differences in abiotic factors, such as frequency of flooding and
      hydrologic push. While more than 100 OTUs were identified, the assemblages were
      not as diverse, based on Shannon indexes, as bacterial communities from
      oligohaline soils. Since natural inland hypersaline soils are relatively
      unstudied, it was not clear what kind of bacteria would be present. The bacterial
      assemblage is predominantly genera typically found in hypersaline systems,
      although some were relatives of microbes common in oligohaline and marine
      environments. The bacterial clones did not reflect wide functional diversity,
      beyond phototrophs, sulfur metabolizers, and numerous heterotrophs.

PMID- 21953015
TI  - Should combination therapy be the paradigm for future nonalcoholic
      steatohepatitis clinical trials?

PMID- 21953016
TI  - Demonstration of inferior vena cava compression by probe pressure during
      subxiphoid echocardiography.
AB  - We sought to compare the inferior vena cava diameter measured by transthoracic
      echocardiography and by transesophageal echocardiography in human and animals.
      Transthoracic echocardiography yielded lower inferior vena cava diameter values
      than transesophageal echocardiography. Adult and pediatric intensivists should
      pay attention to the risk of false measurement of the inferior vena cava anterior
      posterior diameter that may be due to compression of the inferior vena cava by
      the sonographic probe when the subxiphoid view is used.

PMID- 21953017
TI  - MRI findings in subacute combined degeneration of the spinal cord in a patient
      with restricted diet.

PMID- 21953018
TI  - Clinical images: Magnetic resonance imaging appearance of alkaptonuria.

PMID- 21953019
TI  - Structural properties of DNA oligomers containing (GACX)(n)  and (GAXC)(n) 
      tandem repeats.
AB  - The antisense DNA sequence of mature mouse micro RNA, miR341, includes three
      repeats of the tetranucleotide (GACC). The -GAC- repeat is known to form a
      parallel duplex, in acidic environments. The thermal melting profile of miR341
      DNA, at pH 4, 5, and 6 indicates the formation of a very stable structure, which
      loses its stability when pH is increased. Thus, the addition of a cytosine at the
      3' end of the (GAC) motif preserves the molecule's potential to fold into an
      unusual structure at low pH. The effect of modifying the nucleotide composition
      of the GACC sequence on the secondary structures formed by oligomers containing
      seven tandem repeats of the altered motifs was examined here. UV melting profiles
      were determined, as a function of pH, for 28-mers of the two series (GAXC)(7) and
      (GACX)(7) (X= A/C/T/G)(.) The sequence (GACC)(7) was found to be extremely
      sensitive to pH variations, with a stable structure formed at pH 5 (T(m) >= 60
      degrees C). NMR spectroscopy established that the low pH structure is not B-DNA.
      (GACA)(7) and (GACT)(7) also formed stable structures at low pH but the addition
      of guanine at the 3'end, as seen in the (GACG) series resulted in the loss of
      this property. Introducing a break in the 5'-GAC-3' motif, explored in the (GAXC)
      series, also inhibits formation of stable structures under acidic conditions.

PMID- 21953020
TI  - Prognostic factors in carpal tunnel syndrome treated with a corticosteroid
      injection.
AB  - INTRODUCTION: Symptoms often return in patients with carpal tunnel syndrome (CTS)
      who are treated with a local corticosteroid injection. We aimed to determine
      prognostic factors for a successful long-term outcome. METHODS: We prospectively
      followed 113 patients who received an injection for CTS. Clinical,
      electrophysiological, and ultrasonographic tests were done at baseline, and
      clinical outcome was evaluated after 1, 3, 6, and 12 months. The primary outcome
      measure for success was no need for additional treatment (e.g., surgery) within 1
      year. RESULTS: After 1 month, most patients improved, but after 12 months 67.4%
      had surgery. Patients with a successful outcome had a lower median nerve
      ultrasonographic cross-sectional area (CSA) at the pisiform bone, a lower
      swelling ratio, and a lower symptom severity score. CONCLUSIONS: Less pronounced
      median nerve swelling measured by ultrasonography may indicate a less severe
      stage of CTS, which is more likely to respond to treatment with a corticosteroid
      injection.

PMID- 21953021
TI  - A Ki67/BCL2 index based on immunohistochemistry is highly prognostic in ER
      positive breast cancer.
AB  - There is an urgent need to improve prognostic classifiers in breast cancer. Ki67
      and B-cell lymphoma 2 protein (BCL2) are established prognostic markers which
      have traditionally been assessed separately, in a dichotomous manner. This study
      was conducted to test the hypothesis that combinatorial assessment of these
      markers would provide superior prognostic information and improve their clinical
      utility. Tissue microarrays were used to assess the expression of Ki67 and BCL2
      in 2749 cases of invasive breast cancer. We devised a Ki67/BCL2 index
      representing the relative expression of each protein and assessed its association
      with breast cancer-specific survival (BCSS) using a Cox proportional-hazards
      model. Based on our findings, an independent cohort of 3992 cases was used to
      validate the prognostic significance of the Ki67/BCL2 index. All survival
      analyses were conducted on complete data as well as data where missing values
      were resolved using multiple imputation. This study complied with reporting
      recommendations for tumour marker prognostic studies (REMARK) criteria. The
      Ki67/BCL2 index showed a significant association with BCSS at 10 years in
      estrogen receptor (ER)-positive disease. In multivariate analysis, adjusting for
      major clinical and molecular markers, the Ki67/BCL2 index retained prognostic
      significance, robustly classifying cases into three risk groups [intermediate-
      versus low-risk hazard ratio (HR), 1.5; 95% confidence interval (95% CI), 1.0
      2.0; p = 0.031; high- versus low-risk HR, 2.6; 95% CI, 1.3-5.0; p = 0.005]. This
      finding was validated in an independent cohort of 3992 tumours containing 2761 ER
      positive tumours (intermediate- versus low-risk HR, 1.7; 95% CI, 1.3-2.1; p <
      0.001; high- versus low-risk HR, 2.0; 95% CI, 1.4-2.9; p < 0.001). Ki67 and BCL2
      can be effectively combined to produce an index which is an independent predictor
      of BCSS in ER-positive breast cancer, enhancing their potential prognostic
      utility.

PMID- 21953022
TI  - Longitudinal changes in social functioning in mildly disabled patients with
      relapsing-remitting multiple sclerosis receiving subcutaneous interferon beta-1a:
      results from the COGIMUS (COGnitive Impairment in MUltiple Sclerosis) study (II).
AB  - PURPOSE: To report longitudinal changes in and explore the influence of cognition
      on social functioning in mildly disabled patients with relapsing-remitting
      multiple sclerosis (RRMS). METHODS: Italian patients (18-50 years) with RRMS and
      Expanded Disability Status Scale (EDSS) score <=4.0 were assigned to interferon
      beta-1a, 44 or 22 MUg subcutaneously three times weekly, and underwent annual
      assessments for social functioning (Environmental Status Scale [ESS]) over 3
      years. RESULTS: Baseline total ESS score did not differ between patients with and
      without cognitive impairment (P = 0.505). Total ESS score remained low (<2.0) and
      stable over 3 years in the whole study population, but worsened slightly when
      assessed by assigned treatment or treatment and baseline cognitive status (both P
      = 0.004), driven mostly by changes in the 'transportation' and
      'financial/economic status' subscales. The strongest independent predictor of
      worsening ESS score was baseline EDSS score. Test-retest analyses confirmed that
      total ESS score and most subscales changed little over 3 years. CONCLUSION: ESS
      scores remained low and changed minimally over 3 years, reflecting the mild
      physical disability and good cognitive performance in this patient population.
      Determining the influence of cognitive function and treatment on longitudinal
      changes in social functioning requires further studies.

PMID- 21953023
TI  - Intratumoral neutrophils and plasmacytoid dendritic cells indicate poor prognosis
      and are associated with pSTAT3 expression in AJCC stage I/II melanoma.
AB  - BACKGROUND: Tumor cell and host immune cell interaction plays a key role in
      carcinogenesis. Signal transducer and activator of transcription 3 (STAT3) is
      constitutively activated in cancer and believed to be an important mediator of
      tumor-induced immunosuppression. This paper aims to describe the prognostic
      impact of neutrophil and dendritic cell infiltration in primary melanoma and the
      association of this infiltration with activated STAT3 (pSTAT3) in primary
      melanoma cells. METHODS: Formalin-fixed, paraffin-embedded primary melanomas from
      186 stage-I/II melanoma patients surgically resected from 1997 to 2000.
      Infiltrating neutrophils (CD66b), dendritic cells (CD123+ and DC-LAMP+), T
      lymphocytes (CD8) and pSTAT3 melanoma cell expression were studied by
      immunohistochemistry and evaluated as present or absent. DC-LAMP+ cell
      infiltration was evaluated as absent/few versus dense. Study endpoints: relapse
      free survival, melanoma-specific, and overall survival. RESULTS: The median
      observation time was 12.2 years (range, 10.4-14.2 years). Fifty-one deaths were
      observed of which 38 (20%) were melanoma-specific. In a multivariate Cox
      proportional hazards model including ulceration and melanoma thickness,
      neutrophil and CD123+ dendritic cell infiltration were independently associated
      with poor prognosis (CD66b: hazard ratio [HR] = 3.13; 95% confidence interval
      [CI], 1.43-6.83; P = .004; CD123: HR = 2.45; 95% CI, 1.22-4.92; P = .012). The
      association between melanoma cell pSTAT3 expression and immune infiltration
      (neutrophils and CD123+ cells) was strong. pSTAT3 expression, CD8 and DC-LAMP
      infiltration were not independently associated with poor prognosis. CONCLUSIONS:
      Neutrophil infiltration and CD123+ dendritic cell infiltration in primary
      melanoma are independently associated with poor prognosis. Melanoma cell
      expression of pSTAT3 is strongly associated with the surrounding immune
      infiltrate.

PMID- 21953024
TI  - Impact of perineal pseudocontinent colostomy on perineal wound healing after
      abdominoperineal resection.
AB  - BACKGROUND: Abdominoperineal resections (APR) for anorectal tumors are associated
      with a high rate of perineal wound complications. The aim of this study was to
      evaluate the impact of pseudocontinent perineal colostomy (PPC) following APR on
      perineal wound healing. METHODS: All patients undergoing APR between 2000 and
      2009 were retrospectively reviewed. Perineal wound healing was compared between
      patients with PPC and those with perineal closure alone. RESULTS: APR was
      performed in 132 patients, including 31 with PPC and 101 with no PPC. Risk
      factors such as radiotherapy, smoking, diabetes mellitus, and obesity were not
      different between the two groups. The PPC group had significantly fewer cases of
      omentoplasty and adenocarcinoma histology. The overall perineal complication
      rate, perineal infection, or wound dehiscence was similar in the two groups, but
      the perineal healing rate at 6 and 12 weeks was significantly increased in the
      PPC group than in the non-PPC group (70.9% vs. 50%, P = 0.04, at 6 weeks; 90.3%
      vs. 73%, P = 0.04, at 12 weeks). CONCLUSIONS: PPC accelerates perineal wound
      healing after APR without decreasing the overall perineal complication rate.

PMID- 21953025
TI  - Self-perceived oral health and associated factors among the elderly in Campinas,
      Southeastern Brazil, 2008-2009.
AB  - OBJECTIVE: To describe self-perceived oral health among elderly people and assess
      associated sociodemographic and clinical factors. METHODS: A cross-sectional
      study was carried out with 876 participants forming a representative sample of
      elderly people (65 years of age or over) in Campinas, Southeastern Brazil, in
      2008-2009. Dental examinations were conducted in accordance with criteria
      standardized by the World Health Organization for epidemiological surveys on oral
      health. Self-perceived oral health was evaluated using the Geriatric Oral Health
      Assessment Index (GOHAI). Individuals were classified according to
      sociodemographic characteristics, dental factors and prevalence of biological
      frailty. Associations were assessed using Poisson regression analysis, taking
      into consideration sample weights and the complex structure of the cluster
      sampling. RESULTS: The subjects' mean age was 72.8 years; 70.1% were women. The
      proportion of the individuals with more than 20 teeth present was 17.2%; 38.2%
      were using full dentures in both arches; 8.5% needed dental prostheses in at
      least one arch. On average, the GOHAI was high: 33.9 (maximum possible: 36.0).
      Retaining 20 teeth or more, using full dentures in both arches, not needing such
      treatment, not presenting any oral mucosa abnormalities and not presenting
      biological frailty were factors significantly associated with better self
      perceived oral health (p < 0.05). CONCLUSIONS: Assessment of self-perceived oral
      health made it possible to identify the main factors associated with this
      outcome. This tool may contribute towards planning dental services and guide
      health promotion strategies for improving the quality of life of individuals
      within this age group.

PMID- 21953026
TI  - Traffic accidents in Brazil from 1998 to 2010: many changes and few effects.
AB  - The paper describes the situation of road traffic accidents in Brazil since 1998,
      when a new Brazilian traffic law was approved, up to the year 2010. A review of
      both academic and non-academic literature was carried out, including journals
      (both indexed and non-indexed), technical reports, author searches, searches in
      paper reference lists and direct contact with researchers. The main problems
      related to road traffic accidents in Brazil identified were the increase in the
      absolute number of deaths and in the mortality rates, a rapid increase in the
      number of motorcycles, and drink & driving. Influent authors in the field and
      centers of expertise were identified. Some potential solutions are presented by
      the authors, who suggest that the public offices related to traffic regulation
      and control are not taking suitable measures for control and reduction of road
      traffic accidents.

PMID- 21953027
TI  - [Unexplained fever and B-symptoms in a young male Black African].
AB  - An immunocompetent Nigerian developed a fulminant hemophagocytic
      lymphohistiocytosis due to Epstein-Barr virus reactivation. The patient initially
      presented with fever, hepatosplenomegaly and pancytopenia. The clinical status of
      our patient deteriorated quickly despite treatment with corticoids. Escalation of
      immunosuppressive treatment was not possible. He died of lung, liver and
      circulatory failure in our intensive care unit.Hemophagocytic lymphohistiocytosis
      is a rare disease characterized by inflammation due to prolonged and excessive
      activation of antigen-presenting cells. High plasma ferritin levels and
      phagocytosis of hematopoetic cells in bone marrow, spleen and liver lead to the
      diagnosis. Hemophagocytic lymphohistiocytosis should therefore be included in the
      differential diagnosis in patients with persistent fever, hepatosplenomegaly and
      cytopenia.

PMID- 21953028
TI  - Unusual augmentation of germline genome size in Cyclops kolensis (Crustacea,
      Copepoda): further evidence in support of a revised model of chromatin
      diminution.
AB  - Embryonic chromatin diminution, the selective excision of large amounts of
      heterochromatic DNA from presomatic cell lineages, provides an example of an
      unusually large augmentation of the germline genome and raises questions
      regarding the source of the increased amount of DNA and its relevance to the
      biology of the organism. DNA levels in adult germ cell nuclei of the copepod
      Cyclops kolensis were determined by DNA-Feulgen cytophotometry and compared with
      those of somatic nuclei of adults and both pre- and postdiminuted embryos from
      the same mothers. Almost 75 pg DNA/nucleus is excised by diminution, resulting in
      the return of each generation to the approximately 1 pg DNA/nucleus level found
      for adult soma. To account for the increase in DNA levels of germ cells observed
      here, we propose alternative hypotheses to the original model of chromatin
      diminution: (1) repetitive endocycles or (2) proliferation of genetic elements.
      Specific tests for these hypotheses using next-generation sequencing and
      quantitative cytophotometry, as well as the functional significance of germ cell
      DNA augmentation to the copepod, are discussed.

PMID- 21953029
TI  - Silk tape nanostructure and silk gland anatomy of trichoptera.
AB  - Caddisflys (order Trichoptera) construct elaborate protective shelters and food
      harvesting nets with underwater adhesive silk. The silk fiber resembles a
      nanostructured tape composed of thousands of nanofibrils (~ 120 nm) oriented with
      the major axis of the fiber, which in turn are composed of spherical subunits.
      Weaker lateral interactions between nanofibrils allow the fiber to conform to
      surface topography and increase contact area. Highly phosphorylated (pSX)(4)
      motifs in H-fibroin blocks of positively charged basic residues are conserved
      across all three suborders of Trichoptera. Electrostatic interactions between the
      oppositely charged motifs could drive liquid-liquid phase separation of silk
      fiber precursors into a complex coacervates mesophase. Accessibility of
      phosphoserine to an anti-phosphoserine antibody is lower in the lumen of the silk
      gland storage region compared to the nascent fiber formed in the anterior
      conducting channel. The phosphorylated motifs may serve as a marker for the
      structural reorganization of the silk precursor mesophase into strongly
      refringent fibers. The structural change occurring at the transition into the
      conducting channel makes this region of special interest. Fiber formation from
      polyampholytic silk proteins in Trichoptera may suggest a new approach to create
      synthetic silk analogs from water-soluble precursors.

PMID- 21953030
TI  - Analysis of acute-phase proteins, AHSG, C3, CLI, HP and SAA, reveals distinctive
      expression patterns associated with breast, colorectal and lung cancer.
AB  - Early detection, clinical management and disease recurrence monitoring are
      critical areas in cancer treatment in which specific biomarker panels are likely
      to be very important in each of these key areas. We have previously demonstrated
      that levels of alpha-2-heremans-schmid-glycoprotein (AHSG), complement component
      C3 (C3), clusterin (CLI), haptoglobin (HP) and serum amyloid A (SAA) are
      significantly altered in serum from patients with squamous cell carcinoma of the
      lung. Here, we report the abundance levels for these proteins in serum samples
      from patients with advanced breast cancer, colorectal cancer (CRC) and lung
      cancer compared to healthy controls (age and gender matched) using commercially
      available enzyme-linked immunosorbent assay kits. Logistic regression (LR) models
      were fitted to the resulting data, and the classification ability of the proteins
      was evaluated using receiver-operating characteristic curve and leave-one-out
      cross-validation (LOOCV). The most accurate individual candidate biomarkers were
      C3 for breast cancer [area under the curve (AUC) = 0.89, LOOCV = 73%], CLI for
      CRC (AUC = 0.98, LOOCV = 90%), HP for small cell lung carcinoma (AUC = 0.97,
      LOOCV = 88%), C3 for lung adenocarcinoma (AUC = 0.94, LOOCV = 89%) and HP for
      squamous cell carcinoma of the lung (AUC = 0.94, LOOCV = 87%). The best dual
      combination of biomarkers using LR analysis were found to be AHSG + C3 (AUC =
      0.91, LOOCV = 83%) for breast cancer, CLI + HP (AUC = 0.98, LOOCV = 92%) for CRC,
      C3 + SAA (AUC = 0.97, LOOCV = 91%) for small cell lung carcinoma and HP + SAA for
      both adenocarcinoma (AUC = 0.98, LOOCV = 96%) and squamous cell carcinoma of the
      lung (AUC = 0.98, LOOCV = 84%). The high AUC values reported here indicated that
      these candidate biomarkers have the potential to discriminate accurately between
      control and cancer groups both individually and in combination with other
      proteins.

PMID- 21953031
TI  - Evaluation of the ESPLINE(r) Influenza A & B-N assay for the detection of
      influenza A and B in nasopharyngeal aspirates.
AB  - Several direct antigen tests for the detection of influenza often lack
      sensitivity compared to immunofluorescence (IF) on the specimens and viral
      culture (VC). We evaluated the performance of a rapid test, the ESPLINE(r)
      Influenza A & B-N assay. A total of 302 respiratory specimens were collected at
      the University Hospital of Antwerp. A first group of 60 samples taken during the
      H1N1 outbreak (2009-2010) and a second group of 242 samples stored during the
      seasonal influenza epidemics (2000-2009) were analyzed with the ESPLINE(r) test.
      A subset of samples were also evaluated with the BinaxNOW Influenza and the
      Clearview Exact Influenza. The results were compared to IF on the specimens, VC
      with IF, and the combination of both, which was considered as the gold standard.
      The ESPLINE(r) test's overall sensitivity and specificity were 91% and 97%,
      during the H1N1 season 80% and 93%, and for the detection of seasonal influenza
      93% and 97%, respectively. In comparison to the BinaxNOW Influenza and the
      Clearview Exact Influenza, all tests demonstrated a similar specificity of 92.0
      100% but a significantly different sensitivity of 44.4-86.0%, with the ESPLINE(r)
      test being significantly more sensitive. Due to its very good performance and
      simplicity, the ESPLINE(r) test facilitates urgent testing. The test seems less
      sensitive to detect H1N1 compared to seasonal influenza, although the difference
      is borderline not significant (p = 0.067).

PMID- 21953032
TI  - Population genetic structure of Guizhou snub-nosed monkeys (Rhinopithecus
      brelichi) as inferred from mitochondrial control region sequences, and comparison
      with R. roxellana and R. bieti.
AB  - The Guizhou snub-nosed monkey (Rhinopithecus brelichi) is a primate species
      endemic to the Wuling Mountains in southern China. With a maximum of 800 wild
      animals, the species is endangered and one of the rarest Chinese primates. To
      assess the genetic diversity within R. brelichi and to analyze its genetic
      population structure, we collected fecal samples from the wild R. brelichi
      population and sequenced the hypervariable region I of the mitochondrial control
      region from 141 individuals. We compared our data with those from the two other
      Chinese snub-nosed species (R. roxellana, R. bieti) and reconstructed their
      phylogenetic relationships and divergence times. With only five haplotypes and a
      maximum of 25 polymorphic sites, R. brelichi shows the lowest genetic diversity
      in terms of haplotype diversity (h), nucleotide diversity (pi), and average
      number of pairwise nucleotide differences (Pi). The most recent common ancestor
      of R. brelichi lived ~0.36 million years ago (Ma), thus more recently than those
      of R. roxellana (~0.91 Ma) and R. bieti (~1.33 Ma). Phylogenetic analysis and
      analysis of molecular variance revealed a clear and significant differentiation
      among the three Chinese snub-nosed monkey species. Population genetic analyses
      (Tajima's D, Fu's F(s) , and mismatch distribution) suggest a stable population
      size for R. brelichi. For the other two species, results point in the same
      direction, but population substructure possibly introduces some ambiguity.
      Because of the lower genetic variation, the smaller population size and the more
      restricted distribution, R. brelichi might be more vulnerable to environmental
      changes or climate oscillations than the other two Chinese snub-nosed monkey
      species. Am J Phys Anthropol, 2012. (c) 2011 Wiley Periodicals, Inc.

PMID- 21953033
TI  - Brain abscess caused by Lactococcus lactis cremoris in a child.
AB  - Lactococcus lactis cremoris infections are very rare in humans. It is recognized
      as a commensal organism of mucocutaneous surfaces of cattle, and is occasionally
      isolated from human mucocutaneous surfaces. We report a brain abscess caused by
      L. lactis cremoris in an immunocompetent child. A 19-month-old female patient was
      admitted with fever and vomiting. Brain computed tomography (CT) revealed brain
      abscess. L. lactis cremoris was isolated from culture of the abscess material.
      The patient was treated with pus drainage from brain abscess and antibiotics
      including vancomycin and meropenem. The patient recovered completely. To our
      knowledge, this is the first report of a L. lactis cremoris infection in
      children.

PMID- 21953034
TI  - Identification of host-specific Bacteroidales 16S rDNA sequences from human
      sewage and ruminant feces.
AB  - The need to identify the source of fecal contamination of water has led to the
      development of various fecal source identification methods, a field known as
      microbial source tracking (MST). One promising method of MST focuses on fecal
      members of the order Bacteroidales, some of which exhibit a high degree of host
      specificity. In order to identify host-specific Bacteroidales genetic markers, a
      ~1060 bp section of Bacteroidales 16S rDNA was amplified from human sewage (n =
      6), and bovine (n = 6) and ovine fecal (n = 5) samples and used for the
      generation of three clone libraries. Phylogenetic analysis of sequences from the
      three clone libraries revealed that the Bacteroidales species found in both human
      sewage and bovine and ovine feces were a highly diverse group of organisms, many
      of which were not represented by previously characterised 16S rDNA. Ovine and
      bovine feces appear to host similar populations of Bacteroidales species and
      these species were more diverse and less closely related to cultivated species
      than the Bacteroidales population found in human sewage. Species of Bacteroidales
      from the ruminant and human feces formed isolated clusters containing putatively
      host-specific sequences. These sequences were subsequently exploited for the
      design of host-specific primers which were used in MST studies.

PMID- 21953035
TI  - Focus in honor of Marvin L. Vestal, recipient of the 2010 Award for a
      Distinguished Contribution in Mass Spectrometry.

PMID- 21953036
TI  - The future of biological mass spectrometry.
AB  - Biological applications of mass spectrometry have grown exponentially since the
      discovery of MALDI and electrospray ionization techniques. This growth has been
      further fueled by the massive volume of DNA sequence information that is now
      available. An ambitious goal of some of this research is to monitor the level and
      modification of all proteins and metabolites in a biological sample such as
      plasma. A major research effort in mass spectrometry and related disciplines has
      been expended over the past several years toward reaching this and other less
      ambitious goals, and considerable progress has been made; but the presently
      available tools are clearly not sufficient for these very difficult tasks. In
      this "critical insight" discussion we suggest that recent advances in time-of
      flight (TOF) technology with MALDI ionization may provide some important new
      tools for achieving the goals of biological research.

PMID- 21953037
TI  - Mass spectrometric immunoassay revisited.
AB  - The progressive understanding and improvement of matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS), realized
      over the years through the considerable efforts of Dr. Marvin Vestal, have made
      possible numerous comparable efforts involving its application in the biological
      sciences. Here we revisit the concepts behind one such analytical approach, Mass
      Spectrometric Immunoassay, which is designed to selectively detect and quantify
      proteins present in biological milieu.

PMID- 21953038
TI  - Production of reliable MALDI spectra with quality threshold clustering of
      replicates.
AB  - We present the first application of the quality threshold (QT) clustering
      algorithm to mass spectrometry (MS) data. The unique abilities of QT clustering
      to yield precision nodes that are commensurate with the mass measurement
      precision of the instrument are exploited to generate a consensus spectrum out of
      multiple replicate spectra. The spectral dot product and confidence intervals are
      used as a tool for evaluating the similarity and reproducibility between the
      consensus and replicates. The method is equally applicable to high and low
      resolution measurements. This paper demonstrates applications to linear spectra
      from a matrix assisted laser desorption ionization (MALDI) time of flight (TOF)
      instrument as well as peptide fragmentation data obtained from a TOF/TOF after
      unimolecular decomposition. The advantages of clustering to mitigate the inherent
      precision the shortcomings of MALDI data are discussed.

PMID- 21953039
TI  - Compelling evidence for Lucky Survivor and gas phase protonation: the unified
      MALDI analyte protonation mechanism.
AB  - This work experimentally verifies and proves the two long since postulated matrix
      assisted laser desorption/ionization (MALDI) analyte protonation pathways known
      as the Lucky Survivor and the gas phase protonation model. Experimental
      differentiation between the predicted mechanisms becomes possible by the use of
      deuterated matrix esters as MALDI matrices, which are stable under typical sample
      preparation conditions and generate deuteronated reagent ions, including the
      deuterated and deuteronated free matrix acid, only upon laser irradiation in the
      MALDI process. While the generation of deuteronated analyte ions proves the gas
      phase protonation model, the detection of protonated analytes by application of
      deuterated matrix compounds without acidic hydrogens proves the survival of
      analytes precharged from solution in accordance with the predictions from the
      Lucky Survivor model. The observed ratio of the two analyte ionization processes
      depends on the applied experimental parameters as well as the nature of analyte
      and matrix. Increasing laser fluences and lower matrix proton affinities favor
      gas phase protonation, whereas more quantitative analyte protonation in solution
      and intramolecular ion stabilization leads to more Lucky Survivors. The presented
      results allow for a deeper understanding of the fundamental processes causing
      analyte ionization in MALDI and may alleviate future efforts for increasing the
      analyte ion yield.

PMID- 21953040
TI  - Identification of nitrotyrosine containing peptides using combined fractional
      diagonal chromatography (COFRADIC) and off-line nano-LC-MALDI.
AB  - Protein nitration take place on tyrosine residues under oxidative stress
      conditions and may influence a number of processes including enzyme activity,
      protein-protein interactions and phospho-tyrosine signalling pathways. Nitrated
      proteins have been identified in a number of diseases, however, the study of
      these proteins has been compromised by the lack of good methods for identifying
      nitrated proteins, their nitration sites and the level of nitration. Here, we
      present a method for identification of nitrated peptides that allows the site
      specific assignment of nitration, is easy to use and reproducible, and opens up
      for the possibility to quantify the level of nitration of specific peptides as
      function of different oxidative conditions, namely combined fractional diagonal
      chromatography (COFRADIC) in combination with off-line nano-LC-MALDI. We identify
      six nitrated peptides from in vitro nitrated bovine serum albumin and propose
      that automated COFRADIC using nano-LC and off-line MALDI-MS might be a
      possibility for identification of tyrosine nitrated proteins and the nitration
      sites in complex samples.

PMID- 21953041
TI  - Electron transfer dissociation of milk oligosaccharides.
AB  - For structural identification of glycans, the classic collision-induced
      dissociation (CID) spectra are dominated by product ions that derived from
      glycosidic cleavages, which provide only sequence information. The peaks from
      cross-ring fragmentation are often absent or have very low abundances in such
      spectra. Electron transfer dissociation (ETD) is being applied to structural
      identification of carbohydrates for the first time, and results in some new and
      detailed information for glycan structural studies. A series of linear milk
      sugars was analyzed by a variety of fragmentation techniques such as MS/MS by CID
      and ETD, and MS(3) by sequential CID/CID, CID/ETD, and ETD/CID. In CID spectra,
      the detected peaks were mainly generated via glycosidic cleavages. By comparison,
      ETD generated various types of abundant cross-ring cleavage ions. These
      complementary cross-ring cleavages clarified the different linkage types and
      branching patterns of the representative milk sugar samples. The utilization of
      different MS(3) techniques made it possible to verify initial assignments and to
      detect the presence of multiple components in isobaric peaks. Fragment ion
      structures and pathways could be proposed to facilitate the interpretation of
      carbohydrate ETD spectra, and the main mechanisms were investigated. ETD should
      contribute substantially to confident structural analysis of a wide variety of
      oligosaccharides.

PMID- 21953042
TI  - MALDI mass spectrometric imaging of lipids in rat brain injury models.
AB  - Matrix-assisted laser desorption ionization/ionization imaging mass spectrometry
      (MALDI IMS) with a time-of-flight analyzer was used to characterize the
      distribution of lipid molecular species in the brain of rats in two injury
      models. Ischemia/reperfusion injury of the rat brain after bilateral occlusion of
      the carotid artery altered appearance of the phospholipids present in the
      hippocampal region, specifically the CA1 region. These brain regions also had a
      large increase in the ion abundance at m/z 548.5 and collisional activation
      supported identification of this ion as arising from ceramide (d18:1/18:0), a
      lipid known to be associated with cellular apoptosis. Traumatic brain injury
      model in the rat was examined by MALDI IMS and the area of damage also showed an
      increase in ceramide (d18:1/18:0) and a remarkable loss of signal for the
      potassium adduct of the most abundant phosphocholine molecular species 16:0/18:1
      (PC) with a corresponding increase in the sodium adduct ion. This change in PC
      alkali attachment ion was suggested to be a result of edema and influx of
      extracellular fluid likely through a loss of Na/K-ATPase caused by the injury.
      These studies reveal the value of MALDI IMS to examine tissues for changes in
      lipid biochemistry and will provide data needed to eventually understand the
      biochemical mechanisms relevant to tissue injury.

PMID- 21953043
TI  - High-speed MALDI-TOF imaging mass spectrometry: rapid ion image acquisition and
      considerations for next generation instrumentation.
AB  - A prototype matrix-assisted laser desorption ionization time-of-flight (MALDI
      TOF) mass spectrometer has been used for high-speed ion image acquisition. The
      instrument incorporates a Nd:YLF solid state laser capable of pulse repetition
      rates up to 5 kHz and continuous laser raster sampling for high-throughput data
      collection. Lipid ion images of a sagittal rat brain tissue section were
      collected in 10 min with an effective acquisition rate of roughly 30 pixels/s.
      These results represent more than a 10-fold increase in throughput compared with
      current commercially available instrumentation. Experiments aimed at improving
      conditions for continuous laser raster sampling for imaging are reported,
      highlighting proper laser repetition rates and stage velocities to avoid signal
      degradation from significant oversampling. As new high spatial resolution and
      large sample area applications present themselves, the development of high-speed
      microprobe MALDI imaging mass spectrometry is essential to meet the needs of
      those seeking new technologies for rapid molecular imaging.

PMID- 21953044
TI  - Towards understanding the tandem mass spectra of protonated oligopeptides. 2: The
      proline effect in collision-induced dissociation of protonated Ala-Ala-Xxx-Pro
      Ala (Xxx = Ala, Ser, Leu, Val, Phe, and Trp).
AB  - The product ion spectra of proline-containing peptides are commonly dominated by
      y(n) ions generated by cleavage at the N-terminal side of proline residues. This
      proline effect is investigated in the current work by collision-induced
      dissociation (CID) of protonated Ala-Ala-Xxx-Pro-Ala (Xxx includes Ala, Ser, Leu,
      Val, Phe, and Trp) in an electrospray/quadrupole/time-of-flight (QqTOF) mass
      spectrometer and by quantum chemical calculations on protonated Ala-Ala-Ala-Pro
      Ala. The CID spectra of all investigated peptides show a dominant y(2) ion (Pro
      Ala sequence). Our computational results show that the proline effect mainly
      arises from the particularly low threshold energy for the amide bond cleavage N
      terminal to the proline residue, and from the high proton affinity of the proline
      containing C-terminal fragment produced by this cleavage. These theoretical
      results are qualitatively supported by the experimentally observed y(2)/b(3)
      abundance ratios for protonated Ala-Ala-Xxx-Pro-Ala (Xxx = Ala, Ser, Leu, Val,
      Phe, and Trp). In the post-cleavage phase of fragmentation the N-terminal
      oxazolone fragment with the Ala-Ala-Xxx sequence and Pro-Ala compete for the
      ionizing proton for these peptides. As the proton affinity of the oxazolone
      fragment increases, the y(2)/b(3) abundance ratio decreases.

PMID- 21953045
TI  - Differentiation of protonated aromatic regioisomers related to lignin by
      reactions with trimethylborate in a Fourier transform ion cyclotron resonance
      mass spectrometer.
AB  - Several lignin model compounds were examined to test whether gas-phase ion
      molecule reactions of trimethylborate (TMB) in a FTICR can be used to
      differentiate the ortho-, meta-, and para-isomers of protonated aromatic
      compounds, such as those formed during degradation of lignin. All three
      regioisomers could be differentiated for methoxyphenols and hydroxyphenols.
      However, only the differentiation of the ortho-isomer from the meta- and para
      isomers was possible for hydroxyacetophenones and hydroxybenzoic acids.
      Consideration of the previously reported proton affinities at all basic sites in
      the isomeric hydroxyphenols, and the calculated proton affinities at all basic
      sites in the three methoxyphenol isomers, revealed that the proton affinities of
      the analytes relative to that of TMB play an important role in determining
      whether and how they react with TMB. The loss of two methanol molecules (instead
      of one) from the adducts formed with TMB either during ion-molecule reactions, or
      during sustained-off resonance irradiated collision-activated dissociation of the
      ion-molecule reaction products, revealed the presence of two functionalities in
      almost all the isomers. This finding supports earlier results suggesting that TMB
      can be used to count the functionalities in unknown oxygen-containing analytes.

PMID- 21953046
TI  - Negative ion CID fragmentation of O-linked oligosaccharide aldoses--charge
      induced and charge remote fragmentation.
AB  - Collision induced dissociation (CID) fragmentation was compared between reducing
      and reduced sulfated, sialylated, and neutral O-linked oligosaccharides. It was
      found that fragmentation of the [M - H](-) ions of aldoses with acidic residues
      gave unique Z-fragmentation of the reducing end GalNAc containing the acidic C-6
      branch, where the entire C-3 branch was lost. This fragmentation pathway, which
      is not seen in the alditols, showed that the process involved charge remote
      fragmentation catalyzed by a reducing end acidic anomeric proton. With structures
      containing sialic acid on both the C-3 and C-6 branch, the [M - H](-) ions were
      dominated by the loss of sialic acid. This fragmentation pathway was also
      pronounced in the [M - 2H](2-) ions revealing both the C-6 Z-fragment plus its
      complementary C-3 C-fragment in addition to glycosidic and cross ring
      fragmentation. This generation of the Z/C-fragment pairs from GalNAc showed that
      the charges were not participating in their generation. Fragmentation of neutral
      aldoses showed pronounced Z-fragmentation believed to be generated by proton
      migration from the C-6 branch to the negatively charged GalNAc residue followed
      by charge remote fragmentation similar to the acidic oligosaccharides. In
      addition, A-type fragments generated by charge induced fragmentation of neutral
      oligosaccharides were observed when the charge migrated from C-1 of the GalNAc to
      the GlcNAc residue followed by rearrangement to accommodate the (0,2)A
      fragmentation. LC-MS also showed that O-linked aldoses existed as interchangeable
      alpha/beta pyranose anomers, in addition to a third isomer (25% of the total free
      aldose) believed to be the furanose form.

PMID- 21953047
TI  - Evaluation of the performance of small diode pumped UV solid state (DPSS) Nd:YAG
      lasers as new radiation sources for atmospheric pressure laser ionization mass
      spectrometry (APLI-MS).
AB  - The performance of a KrF* bench top excimer laser and a compact diode pumped UV
      solid state (DPSS) Nd:YAG laser as photo-ionizing source in LC-APLI MS is
      compared. The commonly applied bench-top excimer laser, operating at 248 nm,
      provides power densities of the order of low MW/cm(2) on an illuminated area of
      0.5 cm(2) (8 mJ/pulse, 5 ns pulse duration, beam waist area 0.5 cm(2), 3
      MW/cm(2)). The DPSS laser, operating at 266 nm, provides higher power densities,
      however, on a two orders of magnitude smaller illuminated area (60 MUJ/pulse, 1
      ns pulse duration, beam waist area 2 * 10(-3) cm(2), 30 MW/cm(2)). In a common LC
      APLI MS setup with direct infusion of a 10 nM pyrene solution, the DPSS laser
      yields a significantly smaller ion signal (0.9%) and signal to noise ratio (1.4%)
      compared with the excimer laser. With respect to the determined low detection
      limits (LODs) for PAHs of 0.1 fmol using an excimer laser, LODs in DPSS laser LC
      APLI MS in the low pmol regime are expected. The advantages of the DPSS laser
      with respect to applicability (size, cost, simplicity) may render this light
      source the preferred one for APLI applications not focusing on ultimately high
      sensitivities. Furthermore, the impact of adjustable ion source parameters on the
      performance of both laser systems is discussed in terms of the spatial
      sensitivity distribution described by the distribution of ion acceptance (DIA)
      measurements. Perspectives concerning the impact on future APLI-MS applications
      are given.

PMID- 21953048
TI  - Expansion cooling in the matrix plume is under-recognized in MALDI mass
      spectrometry.
AB  - Time-of-flight (TOF) mass spectra for a peptide (Y(6)) were obtained by utilizing
      matrix-assisted infrared laser desorption ionization (IR-MALDI) with glycerol as
      the matrix and by ultraviolet MALDI with alpha-cyano-4-hydroxycinnamic acid
      (CHCA), sinapinic acid (SA), and 2,5-dihydroxybenzoic acid (DHB). Collisional
      activation during ion extraction and exothermicity in the gas-phase proton
      transfer were found to be unimportant as the driving forces for in-source (ISD)
      and post-source (PSD) decays, indicating that the thermal energy acquired during
      photo-ablation is responsible for their occurrence. The temperatures of [Y(6) +
      H](+) in the 'early' and 'late' matrix plumes were estimated by the kinetic
      analysis of the ISD and PSD yields, respectively. The order of the temperatures
      was glycerol < DHB ~ SA < CHCA in the early plume and glycerol < DHB < SA < CHCA
      in the late plume. For each matrix, the temperature in the late plume was lower
      than in the early plume by 300-400 K, which was attributed to expansion cooling.
      The model (thermalization followed by expansion cooling) proposed to explain the
      occurrence of both rapid ISD and slow PSD is not only in sharp contrast with but
      also mutually exclusive with the prevailing explanation that the exothermicity in
      proton transfer and in-plume collisional activation are the driving forces for
      ion fragmentation in MALDI. The model also explains why MALDI is more successful
      for mass spectrometry of labile molecules than other desorption techniques that
      do not utilize a matrix. Factors affecting the plume temperature are also
      discussed.

PMID- 21953049
TI  - Digital imaging mass spectrometry.
AB  - Methods to visualize the two-dimensional (2D) distribution of molecules by mass
      spectrometric imaging evolve rapidly and yield novel applications in biology,
      medicine, and material surface sciences. Most mass spectrometric imagers acquire
      high mass resolution spectra spot-by-spot and thereby scan the object's surface.
      Thus, imaging is slow and image reconstruction remains cumbersome. Here we
      describe an imaging mass spectrometer that exploits the true imaging capabilities
      by ion optical means for the time of flight mass separation. The mass
      spectrometer is equipped with the ASIC Timepix chip as an array detector to
      acquire the position, mass, and intensity of ions that are imaged by matrix
      assisted laser desorption/ionization (MALDI) directly from the target sample onto
      the detector. This imaging mass spectrometer has a spatial resolving power at the
      specimen of (84 +/- 35) MUm with a mass resolution of 45 and locates atoms or
      organic compounds on a surface area up to ~2 cm(2). Extended laser spots of ~5
      mm(2) on structured specimens allows parallel imaging of selected masses. The
      digital imaging mass spectrometer proves high hit-multiplicity, straightforward
      image reconstruction, and potential for high-speed readout at 4 kHz or more. This
      device demonstrates a simple way of true image acquisition like a digital
      photographic camera. The technology may enable a fast analysis of biomolecular
      samples in near future.

PMID- 21953050
TI  - Metastable atom-activated dissociation mass spectrometry of phosphorylated and
      sulfonated peptides in negative ion mode.
AB  - The dissociation behavior of phosphorylated and sulfonated peptide anions was
      explored using metastable atom-activated dissociation mass spectrometry (MAD-MS)
      and collision-induced dissociation (CID). A beam of high kinetic energy helium
      (He) metastable atoms was exposed to isolated phosphorylated and sulfonated
      peptides in the 3- and 2- charge states. Unlike CID, where phosphate losses are
      dominant, the major dissociation channels observed using MAD were C(alpha) - C
      peptide backbone cleavages and neutral losses of CO(2), H(2)O, and [CO(2) +
      H(2)O] from the charge reduced (oxidized) product ion, consistent with an
      electron detachment dissociation (EDD) mechanism such as Penning ionization.
      Regardless of charge state or modification, MAD provides ample backbone cleavages
      with little modification loss, which allows for unambiguous PTM site
      determination. The relative abundance of certain fragment ions in MAD is also
      demonstrated to be somewhat sensitive to the number and location of deprotonation
      sites, with backbone cleavage somewhat favored adjacent to deprotonated sites
      like aspartic acid residues. MAD provides a complementary dissociation technique
      to CID, ECD, ETD, and EDD for peptide sequencing and modification identification.
      MAD offers the unique ability to analyze highly acidic peptides that contain few
      to no basic amino acids in either negative or positive ion mode.

PMID- 21953051
TI  - Signal enhancement of abiotically-synthesized RNA oligonucleotides and other
      biopolymers using unmodified fused silica in MALDI-MS.
AB  - Metal is the standard desorption platform for MALDI-MS but other surfaces have
      been shown to offer advantages for particular types of analytes or applications.
      One such substrate is fused silica, which has been employed for matrix-free
      detection of low mass analytes and for affinity MALDI-MS in which binding ligands
      are immobilized at the fused silica surface. The present work reports improved
      MALDI-MS detection of RNA oligonucleotides, including polyA, polyU, and polyA/U,
      at the high end of the mass range when unmodified fused silica is used instead of
      stainless steel as the MALDI target. The RNA oligonucleotides were abiotically
      synthesized from activated monomers on catalytic clay surfaces. Further
      investigation found enhanced signals as well for other anionic biopolymers,
      including DNA oligonucleotides and heparin. Enhancement also was observed for
      dextran, which is neutral, indicating that the effect is not restricted to
      anionic biopolymers. Among more general analytical applications, the results are
      particularly relevant to rapid screening of abiotic RNA polymerization toward
      elucidating pathways to life on Earth.

PMID- 21953052
TI  - Implementing photodissociation in an Orbitrap mass spectrometer.
AB  - We modified a dual pressure linear ion trap Orbitrap to permit infrared
      multiphoton dissociation (IRMPD) in the higher energy collisional dissociation
      (HCD) cell for high resolution analysis. A number of parameters, including the
      pressures of the C-trap and HCD cell, the radio frequency (rf) amplitude applied
      to the C-trap, and the HCD DC offset, were evaluated to optimize IRMPD efficiency
      and maintain a high signal-to-noise ratio. IRMPD was utilized for
      characterization of phosphopeptides, supercharged peptides, and N-terminal
      modified peptides, as well as for top-down protein analysis. The high resolution
      and high mass accuracy capabilities of the Orbitrap analyzer facilitated
      confident assignment of product ions arising from IRMPD.

PMID- 21953053
TI  - From cell regulation to patient survival: 2nd Cancer Immunotherapy and
      Immunomonitoring (CITIM) meeting, Budapest, 2-5 May 2011.

PMID- 21953055
TI  - Reference data for ulnar nerve short segment conduction studies at the elbow.
AB  - INTRODUCTION: The aim of this study was to generate reference data for ulnar
      nerve short segment conduction studies (SSCSs) at 2-cm intervals. METHODS: Ulnar
      nerve SSCS data were collected from dominant and non-dominant arms of 200 healthy
      volunteers. The effects of age, gender, weight, height, and body mass index (BMI)
      on SSCSs were also investigated. RESULTS: High percentile values for short
      segment latency changes varied from 0.4 to 0.7 ms. Ulnar nerve conductions were
      slower in the segments 2 cm below and above the elbow compared with the other
      segments. The amplitude was found not to decrease by >15% in subsequent short
      segments. There were no significant effects of age and gender on the SSCS
      parameters. Conductions over the short segments tended to be faster as BMI
      increased. CONCLUSIONS: Reference values should be determined separately over
      each 2-cm segment, and the effect of BMI should be considered when interpreting
      SSCSs.

PMID- 21953054
TI  - Frequencies of KIT and PDGFRA mutations in the MolecGIST prospective population
      based study differ from those of advanced GISTs.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common human sarcoma. Most
      of the data available on GISTs derive from retrospective studies of patients
      referred to oncology centers. The MolecGIST study sought to determine and
      correlate clinicopathological and molecular characteristics of GISTs. Tumor
      samples and clinical records were prospectively obtained and reviewed for
      patients diagnosed in France during a 24-month period. Five hundred and ninety
      six patients were included, of whom 10% had synchronous metastases. GISTs
      originated from the stomach, small bowel or other site in 56.4, 30.2 and 13.4% of
      cases, respectively. The main prognostic markers, tumor localization, size and
      mitotic index were not independent variables (P < 0.0001). Mutational status was
      determined in 492 (83%) patients, and 138 different mutations were identified.
      KIT and PDGFRA mutations were detected in 348 (71%) and 74 (15%) patients,
      respectively, contrasting with 82.8 and 2.1% in patients with advanced GIST
      (MetaGIST) (P < 0.0001). Further comparison of localized GISTs in the MolecGIST
      cohort with advanced GISTs from previous clinical trials showed that the
      mutations of PDGFRA exon18 (D842V and others) as well as KIT exon11 substitutions
      (W557R and V559D) were more likely to be seen in patients with localized GISTs
      (odds ratio 7.9, 3.1, 2.7 and 2.5, respectively), while KIT exon 9 502_503dup and
      KIT exon 11 557_559del were more frequent in metastatic GISTs (odds ratio of 0.3
      and 0.5, respectively). These data suggest that KIT and PDGFRA mutations and
      standardized mitotic count deserve to be investigated to evaluate the relapse
      risk of GISTs.

PMID- 21953056
TI  - miR-25 targets TNF-related apoptosis inducing ligand (TRAIL) death receptor-4 and
      promotes apoptosis resistance in cholangiocarcinoma.
AB  - It has been established that microRNA expression and function contribute to
      phenotypic features of malignant cells, including resistance to apoptosis.
      Although targets and functional roles for a number of microRNAs have been
      described in cholangiocarcinoma, many additional microRNAs dysregulated in this
      tumor have not been assigned functional roles. In this study, we identify
      elevated miR-25 expression in malignant cholangiocarcinoma cell lines as well as
      patient samples. In cultured cells, treatment with the Smoothened inhibitor,
      cyclopamine, reduced miR-25 expression, suggesting Hedgehog signaling stimulates
      miR-25 production. Functionally, miR-25 was shown to protect cells against TNF
      related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Correspondingly,
      antagonism of miR-25 in culture sensitized cells to apoptotic death.
      Computational analysis identified the TRAIL Death Receptor-4 (DR4) as a potential
      novel miR-25 target, and this prediction was confirmed by immunoblot, cell
      staining, and reporter assays. CONCLUSION: These data implicate elevated miR-25
      levels in the control of tumor cell apoptosis in cholangiocarcinoma. The
      identification of the novel miR-25 target DR4 provides a mechanism by which miR
      25 contributes to evasion of TRAIL-induced cholangiocarcinoma apoptosis.

PMID- 21953058
TI  - Sonographic measurement of corpus spongiosum in male fetuses.
AB  - OBJECTIVE: To establish a nomogram of the corpus spongiosum dimensions in male
      fetuses and to evaluate its correlation with penile length. These references can
      be useful when fetal genital anomalies are suspected, particularly to distinguish
      micropenis from concealed penis cases. METHOD: A cross-sectional prospective
      study was conducted on 486 fetuses of normal singleton pregnancies between 18 and
      40 weeks. Corpus spongiosum length, penile length, penile diameter and scrotal
      diameter were measured by one operator. All measurements were analyzed according
      to gestational age. RESULTS: The four measurements were studied as a function of
      gestational age. Median values, 3(rd) and 97(th) percentiles were determined
      using regression curves. A correlation between penile length and corpus
      spongiosum length (r(2) = 0.845) was observed. CONCLUSION: We established
      measurements of the length of fetal corpus spongiosum and a correlation between
      the former and the penile length. These references can be useful when fetal
      genital anomalies are suspected.

PMID- 21953057
TI  - Microchimerism in the rheumatoid nodules of patients with rheumatoid arthritis.
AB  - OBJECTIVE: The rheumatoid nodule is a lesion commonly found on extraarticular
      areas prone to mechanic trauma. When present with inflammatory symmetric
      polyarthritis, it is pathognomonic of rheumatoid arthritis (RA), an autoimmune
      disease in which naturally acquired microchimerism has previously been described
      and can sometimes contribute to RA risk. Since RA patients harbor microchimerism
      in the blood, we hypothesized that microchimerism is also present in rheumatoid
      nodules and could play a role in rheumatoid nodule formation. This study was
      undertaken to investigate rheumatoid nodules for microchimerism. METHODS:
      Rheumatoid nodules were tested for microchimerism by real-time quantitative
      polymerase chain reaction (qPCR). The rheumatoid nodules of 29 female patients
      were tested for a Y chromosome-specific sequence. After HLA genotyping of
      patients and family members, rheumatoid nodules from 1 man and 14 women were
      tested by HLA-specific qPCR, targeting a nonshared HLA allele of the potential
      microchimerism source. Results were expressed as genome equivalents of
      microchimeric cells per 10(5) patient genome equivalents (GE/10(5)). RESULTS:
      Rheumatoid nodules from 21% of the female patients contained male DNA (range
      <0.5, 10.3 GE/10(5)). By HLA-specific qPCR, 60% of patients were microchimeric
      (range 0, 18.5 GE/10(5)). Combined microchimerism prevalence was 47%. A fetal or
      maternal source was identified in all patients who tested positive by HLA
      specific qPCR. Unexpectedly, a few rheumatoid nodules also contained
      microchimerism without evidence of a fetal or maternal source, suggesting
      alternative sources. CONCLUSION: Our findings indicate that microchimerism is
      frequently present in the rheumatoid nodules of RA patients. Since microchimerism
      is genetically disparate, whether microchimerism in rheumatoid nodules serves as
      an allogeneic stimulus or allogeneic target warrants further investigation.

PMID- 21953059
TI  - Thrombin induces osteosarcoma growth, a function inhibited by low molecular
      weight heparin in vitro and in vivo: procoagulant nature of osteosarcoma.
AB  - BACKGROUND: Procoagulant states, leading to activation of the coagulation
      protease thrombin, are common in cancer and portend a poor clinical outcome.
      Although procoagulant states in osteosarcoma patients have been described,
      studies exploring osteosarcoma cells' ability to directly contribute to
      procoagulant activity have not been reported. This study explores the hypothesis
      that osteosarcoma can regulate thrombin generation and proliferate in response to
      thrombin, and that attenuating thrombin generation with anticoagulants can slow
      tumor growth. METHODS: Pathologic analysis of osteosarcoma with adjacent venous
      thrombus was performed. In vitro proliferation assays, cell-based coagulant
      activity assays, and quantification of coagulation cofactor expression were
      performed on human and murine osteosarcoma cell lines with varying
      aggressiveness. The efficacy of low molecular weight heparin (LMWH) attenuation
      of tumor-dependent thrombin generation and growth in vitro and in vivo was
      determined. RESULTS: Venous thrombi adjacent to osteosarcoma were found to harbor
      tumor surrounded by fibrin expressing coagulation cofactors, a finding associated
      with poor clinical outcome. More aggressive osteosarcoma cell lines had greater
      surface expression of procoagulant factors and generated more thrombin than less
      aggressive cell lines and were found to proliferate in response to thrombin.
      Treatment with LMWH reduced in vitro osteosarcoma proliferation and procoagulant
      activity as well as tumor growth in vivo. CONCLUSIONS: These findings suggest
      that elements of the coagulation cascade may play a role in and represent a
      pharmaceutical target to disrupt osteosarcoma growth. They also have broader
      implications, as they suggest that, to be effective, dosing of anticoagulants
      must take into account an individual tumor's capacity to generate thrombin.

PMID- 21953060
TI  - Comparison of surgical outcomes between endoscopic and robotic thyroidectomy.
AB  - OBJECTIVES: Gasless transaxillary endoscopic thyroidectomy offers a distinct
      advantage over the conventional open operation because it leaves no visible neck
      scar. Indications have expanded with the development of new surgical techniques
      and instruments. However, because of the two-dimensional view and the nonflexible
      instruments, this procedure is not easily amenable for total thyroidectomy. So,
      robotic surgery has been introduced and offers improved visualization and
      dexterity. But, it remains unclear whether robotic thyroidectomy offers any
      potential benefits over endoscopic thyroidectomy. The aim of this present study
      was to determine whether robotic surgery is superior to endoscopic surgery
      through a comparison of surgical outcomes. METHODS: Between May 2009 and February
      2011, 165 patients underwent endoscopic thyroidectomy (endoscopy group) and 46
      patients underwent robotic thyroidectomy (robot group). A gasless transaxillary
      approach was used in both groups. The two groups were compared in terms of
      patient characteristics, perioperative clinical results, pathologic findings, and
      postoperative complication. RESULTS: Both patient groups were similar in terms of
      patient characteristics, mean number of retrieved central lymph nodes,
      pathological features, length of hospital stays, postoperative complication rate,
      and serum Tg level. However, the mean total operation time for thyroidectomy was
      126.2 +/- 37.84 min in the endoscopy group and 179.6 +/- 44.34 min in the robot
      group (P < 0.001). Postoperative total drainage for lobectomy was 153.3 +/- 45.64
      for the endoscopy group and 179.9 +/- 49.15 for the robot group (P = 0.031). Cost
      effectiveness is also an important consideration when evidence for predominance
      of two surgical techniques is lacking. The mean cost of robotic thyroidectomy was
      $6,655, compared with $829 for endoscopic thyroidectomy (P < 0.001). There was no
      significant difference in postoperative complications as hypocalcemia, recurrent
      laryngeal nerve injury, chyle leakage and tracheal injury in the two groups (P =
      0.332). CONCLUSION: Robotic thyroidectomy was lengthier in duration than
      endoscopic thyroidectomy, more costly, and associated with increased
      postoperative drainage with no improvement in oncologic outcomes or complication
      rates. Therefore our data do not support any advantage of robotic surgery over
      endoscopic surgery.

PMID- 21953061
TI  - Relationship between post-traumatic stress disorder and diabetes among 105,180
      asylum seekers in the Netherlands.
AB  - BACKGROUND: Several reports have demonstrated a relationship between post
      traumatic stress disorder (PTSD) and type 2 diabetes (T2DM) mainly in combat
      veterans. The relationship between PTSD and T2DM has not been evaluated among
      vulnerable migrant populations. The main objective of this study was therefore to
      assess the relationship between PTSD and T2DM among asylum seekers in the
      Netherlands. METHODS: Analysis of a national electronic database of the Dutch
      Community Health Services for Asylum seekers aged>=18 years (N=105,180). RESULTS:
      Asylum seekers with PTSD had a higher prevalence of T2DM compared with those
      without PTSD. The age-adjusted prevalence ratios (APR) were 1.40 (95% CI, 1.12
      1.76) in men and 1.22 (95% CI, 0.95-1.56) in women compared with individuals
      without PTSD, respectively. There was an interaction between PTSD and comorbid
      depression (P<0.05) in men and women, indicating that the effect of PTSD and
      comorbid depression on T2DM differed. When the analyses were stratified by
      depression status, among non-depressed group, individuals with PTSD had a higher
      prevalence of T2DM compared with those without PTSD [APR=1.47 (95% CI, 1.15-1.87)
      in men and APR=1.27 (95% CI, 0.97-1.66) in women]. Among the depressed
      individuals, however, there was no association between PTSD and T2DM [APR=0.87
      (95% CI, 0.43-1.76) in men, and APR=1.00, (95% CI, 0.54-1.83) in women].
      CONCLUSION: The findings suggest that history of PTSD is related to high levels
      of T2DM among asylum seekers independent of comorbid depression. Clinicians and
      policy makers need to take PTSD into account when assessing and treating diabetes
      among vulnerable migrant populations.

PMID- 21953062
TI  - Socio-economic position and mental disorders in a working-age Finnish population:
      the health 2000 study.
AB  - BACKGROUND: Mental disorders are more common in people with lower socio-economic
      position (SEP) but it is not known which specific SEP component is most strongly
      linked to poor mental health. We compared the strength of associations of three
      SEP components-occupation, income and education-with common mental disorders in a
      Finnish population. METHODS: Cross-sectional analysis of a nationally
      representative sample of 4561 men and women aged 30-65 years. Mental disorders
      were assessed using the Composite International Diagnostic Interview resulting in
      12-month DSM-IV diagnoses of depressive, anxiety and alcohol use disorders.
      Participants were classified as having low SEP if they worked in a manual
      occupation, lacked secondary-level education or had income below the Organisation
      for Economic Co-operation and Development (OECD) definition of relative poverty.
      RESULTS: In models comparing the simultaneous association of all three socio
      economic indicators with mental disorders, low income was associated with
      increased risk for depressive disorder [odds ratio (OR)=1.73, 95% confidence
      interval (CI) =1.31-2.29] and anxiety disorder (OR=1.56, 95% CI 1.14-2.12).
      Manual occupational class was modestly associated with risk for alcohol use
      disorder (OR=1.44, 95% CI 1.06-1.95). Low income was the only socio-economic
      component associated with psychiatric comorbidity, that is, a combination of
      various disorders within the same individual (OR 2.26, 95% CI 1.52-3.37 for any
      combination). CONCLUSION: Low income seems to be a more important correlate of
      mental disorders than education or occupation in a high-income country such as
      Finland.

PMID- 21953063
TI  - Socio-economic determinants of early discontinuation of anti-depressant treatment
      in young adults.
AB  - BACKGROUND: Early discontinuation of anti-depressant treatment is common. This
      study analysed whether socio-economic factors influence early discontinuation
      among new anti-depressant users aged 20-34 years. METHODS: Our study population
      included all Swedes aged 20-34 years who purchased anti-depressants in 2006 and
      had not purchased such drugs in the preceding 6 months (n = 25,003). We obtained
      prescription data from the Swedish Prescribed Drug Register. Information about
      demographic and socio-economic factors (country of birth, marital status,
      household size, education level, occupation, income and social assistance) was
      collected from Statistics Sweden by record linkage. We defined early
      discontinuation as filling only one anti-depressant prescription within a 6-month
      period. We used multiple logistic regression analysis to analyse the socio
      economic factors associated with early discontinuation. RESULTS: We identified
      6536 individuals (26.1%) as early discontinuers. Early discontinuation was less
      common among women [odds ratio (OR) = 0.82; 95% confidence intervals (CI) 0.75
      0.87] and in those with at least two years of higher education (OR = 0.71; 95% CI
      0.61-0.83), whereas it was more common among those born outside Sweden (OR =
      1.76; 95% CI 1.48-2.10) and those who received social assistance (OR = 1.26; 95%
      CI 1.11-1.44). Compared with selective serotonin re-uptake inhibitors, SSRI,
      early discontinuation was more common among individuals who started treatment
      with a tri-cyclic anti-depressant, TCA, (OR = 2.58; 95% CI 2.24-2.98) or an anti
      depressant other than SSRIs, TCAs or selective serotonin-norepinephrine re-uptake
      inhibitors/norepinephrine (noradrenaline) re-uptake inhibitors (OR = 2.90; 95% CI
      2.05-4.10). CONCLUSION: Early discontinuation occurred more commonly among social
      assistance recipients and those with immigrant background, suggesting that those
      groups might require greater support when initiating anti-depressant therapy.

PMID- 21953064
TI  - Ventilation inhomogeneity in children with primary ciliary dyskinesia.
AB  - BACKGROUND: The lung clearance index (LCI) derived from the multiple breath inert
      gas washout (MBW) test reflects global ventilation distribution inhomogeneity. It
      is more sensitive than forced expiratory volume in 1 s (FEV(1)) for detecting
      abnormal airway function and correlates closely with structural lung damage in
      children with cystic fibrosis, which shares features with primary ciliary
      dyskinesia (PCD). Normalised phase III slope indices S(cond) and S(acin) reflect
      function of the small conducting and acinar airways, respectively. The
      involvement of the peripheral airways assessed by MBW tests has not been
      previously described in PCD. METHODS: A cross-sectional MBW study was performed
      in 27 children and adolescents with verified PCD, all clinically stable and able
      to perform lung function tests. LCI, S(cond) (n=23) and S(acin) (n=23) were
      derived from MBW using a mass spectrometer and sulfur hexafluoride as inert
      marker gas. MBW indices were compared with present age, age at diagnosis and
      spirometry findings, and were related to published normative values. RESULTS:
      LCI, S(cond) and S(acin) were abnormal in 85%, 96% and 78% of patients with PCD
      and in 81%, 93% and 79%, respectively, of 13/27 subjects with normal FEV(1). LCI
      and S(acin) correlated significantly while S(cond) did not correlate with any
      other lung function parameters. None of the lung function measurements correlated
      with age or age at diagnosis. CONCLUSIONS: PCD is characterised by marked
      peripheral airway dysfunction. MBW seems promising in the early detection of lung
      damage, even in young patients with PCD. The relationship of MBW indices to the
      outcome of long-term disease and their role in the management of PCD need to be
      assessed.

PMID- 21953065
TI  - Flight-related complications are infrequent in patients with hereditary
      haemorrhagic telangiectasia/pulmonary arteriovenous malformations, despite low
      oxygen saturations and anaemia.
AB  - Individuals with pulmonary arteriovenous malformations (PAVMs) and hereditary
      haemorrhagic telangiectasia (HHT) commonly have low oxygen saturations and
      anaemia, two parameters generally used to indicate medical fitness to fly. Using
      a retrospective questionnaire-based study, the authors examined in-flight
      complications and predictors in 145 HHT patients (96 with PAVMs) who reported
      3950 flights, totalling 18 943 flight hours. Dyspnoea and thrombotic
      complications were less common than expected, and could not be predicted from sea
      level oxygen saturations or haemoglobin concentrations. Nosebleeds that can bar
      individuals from boarding a flight occurred in 13.6% (11.5% to 15.8%) of long
      haul flights. The findings should influence preflight advice.

PMID- 21953066
TI  - Effect of late preterm birth on longitudinal lung spirometry in school age
      children and adolescents.
AB  - BACKGROUND: Rates of preterm birth have increased in most industrialised
      countries but data on later lung function of late preterm births are limited. A
      study was undertaken to compare lung function at 8-9 and 14-17 years in children
      born late preterm (33-34 and 35-36 weeks gestation) with children of similar age
      born at term (>=37 weeks gestation). Children born at 25-32 weeks gestation were
      also compared with children born at term. METHODS: All births from the Avon
      Longitudinal Study of Parents and Children (n=14 049) who had lung spirometry at
      8-9 years of age (n=6705) and/or 14-17 years of age (n=4508) were divided into
      four gestation groups. RESULTS: At 8-9 years of age, all spirometry measures were
      lower in the 33-34-week gestation group than in controls born at term but were
      similar to the spirometry decrements observed in the 25-32-week gestation group.
      The 35-36-week gestation group and term group had similar values. In the late
      preterm group, at 14-17 years of age forced expiratory volume in 1 s (FEV(1)) and
      forced vital capacity (FVC) were not significantly different from the term group
      but FEV(1)/FVC and forced expiratory flow at 25-75% FVC (FEF(25-75%)) remained
      significantly lower than term controls. Children requiring mechanical ventilation
      in infancy at 25-32 and 33-34 weeks gestation had in general lower airway
      function (FEV(1) and FEF(25-75)) at both ages than those not ventilated in
      infancy. CONCLUSIONS: Children born at 33-34 weeks gestation have significantly
      lower lung function values at 8-9 years of age, similar to decrements observed in
      the 25-32-week group, although some improvements were noted by 14-17 years of
      age.

PMID- 21953067
TI  - [Effects of alcohol and smoking in pregnancy].
AB  - Nicotine and alcohol are legal drugs, which damage not only the health of the
      consumer, but also the society due to health-economic costs. In pregnancy, the
      consequences of alcohol consumption and smoking for the unborn life in pregnancy
      are dramatic. The irreversibly damaging effect of alcohol is proven in each stage
      of the pregnancy, whereby the phase of the organogenesis is the most sensitive
      period. Beside a higher incidence for deformations of all organs, the damage of
      the central nervous system is leading, since mental-intellectual retardation of
      children after alcohol consumption in pregnancy is proven. Smoking in pregnancy
      leads likewise to harmful effects, with the intrauterine growth retardation of
      the fetus being the leading smoking-induced pathology. Smoking- and alcohol
      induced damages for the unborn life are irreversible with no therapeutic options.
      The only therapy is prevention, which means complete cessation of alcohol and
      smoking in pregnancy.

PMID- 21953071
TI  - Hsa-miR-375 is differentially expressed during breast lobular neoplasia and
      promotes loss of mammary acinar polarity.
AB  - Invasive lobular carcinoma (ILC) of the breast, characterized by loss of E
      cadherin expression, accounts for 5-15% of invasive breast cancers and it is
      believed to arise via a linear histological progression. Genomic studies have
      identified a clonal relationship between ILC and concurrent lobular carcinoma in
      situ (LCIS) lesions, suggesting that LCIS may be a precursor lesion. It has been
      shown that an LCIS diagnosis confers a 15-20% risk of progression to ILC over a
      lifetime. Currently no molecular test or markers can identify LCIS lesions likely
      to progress to ILC. Since microRNA (miRNA) expression changes have been detected
      in a number of other cancer types, we explored whether their dysregulation might
      be detected during progression from LCIS to ILC. Using the Illumina miRNA
      profiling platform, designed for simultaneous analysis of 470 mature miRNAs, we
      analysed the profiles of archived normal breast epithelium, LCIS lesions found
      alone, LCIS lesions concurrent with ILC, and the concurrent ILCs as a model of
      linear histological progression towards ILC. We identified two sets of
      differentially expressed miRNAs, the first set highly expressed in normal
      epithelium, including hsa-miR-224, -139, -10b, -450, 140, and -365, and the
      second set up-regulated during lobular neoplasia progression, including hsa-miR
      375, -203, -425-5p, -183, -565, and -182. Using quantitative RT-PCR, we validated
      a trend of increasing expression for hsa-miR-375, hsa-miR-182, and hsa-miR-183
      correlating with ILC progression. As we detected increased expression of hsa-miR
      375 in LCIS lesions synchronous with ILC, we sought to determine whether hsa-miR
      375 might induce phenotypes reminiscent of lobular neoplasia by expressing it in
      the MCF-10A 3D culture model of mammary acinar morphogenesis. Increased
      expression of hsa-miR-375 resulted in loss of cellular organization and
      acquisition of a hyperplastic phenotype. These data suggest that dysregulated
      miRNA expression contributes to lobular neoplastic progression.

PMID- 21953072
TI  - Suspected osseous recurrence visualized on a (68)Ga-DOTATATE PET/CT scan during
      the follow-up of a patient with a resected pulmonary carcinoid tumour.

PMID- 21953073
TI  - Inhibition of Polo-like kinase 1 prevents the growth of metastatic breast cancer
      cells in the brain.
AB  - Few therapeutic strategies exist for the treatment of metastatic tumor cells in
      the brain because the blood-brain barrier (BBB) limits drug access. Thus the
      identification of molecular targets and accompanying BBB permeable drugs will
      significantly benefit brain metastasis patients. Polo-like kinase 1 (Plk1) is an
      attractive molecular target because it is only expressed in dividing cells and
      its expression is upregulated in many tumors. Analysis of a publicly available
      database of human breast cancer metastases revealed Plk1 mRNA expression was
      significantly increased in brain metastases compared to systemic metastases (P =
      0.0018). The selective Plk1 inhibitor, GSK461364A, showed substantial uptake in
      normal rodent brain. Using a breast cancer brain metastatic xenograft model (231
      BR), we tested the efficacy of GSK461364A to prevent brain metastatic
      colonization. When treatment was started 3 days post-injection, GSK461364A at 50
      mg/kg inhibited the development of large brain metastases 62% (P = 0.0001) and
      prolonged survival by 17%. GSK461364A sensitized tumor cells to radiation induced
      cell death in vitro. Previously, it was reported that mutations in p53 might
      render tumor cells more sensitive to Plk1 inhibition; however, p53 mutations are
      uncommon in breast cancer. In a cohort of 41 primary breast tumors and matched
      brain metastases, p53 immunostaining was increased in 61% of metastases; 44% of
      which were associated with primary tumors with low p53. The data suggest that p53
      overexpression occurs frequently in brain metastases and may facilitate
      sensitivity to Plk1 inhibition. These data indicate Plk1 may be a new druggable
      target for the prevention of breast cancer brain metastases.

PMID- 21953074
TI  - CD44 is a biomarker associated with human prostate cancer radiation sensitivity.
AB  - CD44 plays an important role in cancer metastasis, chemotherapy, and radiation
      resistance. The present study investigated the relationship of CD44 expression
      and radioresistance, and the potential mechanisms of CD44 in radiosensitivity
      using prostate cancer (CaP) cell lines. CD44 was knocked down in three CaP cell
      lines (PC-3, PC-3M-luc, and LNCaP) using small interfering RNA (siRNA) and
      clonogenic survival fractions after single dose irradiation were compared before
      and after CD44 knocking down (KD). The effect of radiation on cell cycle
      distribution was examined by flow cytometry and the cell cycle-related protein
      levels of phospho-Chk1 and phospho-Chk2 were ascertained by Western blotting. The
      expression of the DNA double strand break (DSB) marker-gammaH2AX was also
      quantified by immunofluorescence staining. Our results indicate that the down
      regulation of CD44 enhanced radiosensitivity in PC-3, PC-3M-luc, and LNCaP CaP
      cells, the sensitizing enhancement ratio for these cell lines was 2.3, 1.3, and
      1.5, respectively and that the delay of DNA DSB repair in low CD44-expressing KD
      CaP cells correlated with ineffective cell cycle arrest and the delayed
      phosphorylation of Chk1 and Chk2. These findings suggest that CD44 may be a
      valuable biomarker and a predictor of radiosensitivity in CaP treatment.

PMID- 21953075
TI  - Functional mutation analysis of EGFR family genes and corresponding lymph node
      metastases in head and neck squamous cell carcinoma.
AB  - Tumors with certain mutations in the epidermal growth factor receptor (EGFR)
      family genes dramatically respond to EGFR inhibitors. Therefore, these mutations
      are important factors that influence disease progression and patient survival. We
      previously studied the mutation status of EGFR in patients with head and neck
      squamous cell carcinoma (HNSCC). However, the mutation status of lymph node
      metastases and the frequency of mutations in EGFR family genes have not been
      extensively studied. In this study, we sequenced the catalytic domains of the
      three other members of the EGFR family, HER2, HER3, and HER4 in 92 clinical
      samples of HNSCC. We identified a HER2 mutation (K716E) in one sample but no
      mutations were found in HER3 or HER4. Next to investigate the relationship
      between EGFR mutations and tumor metastasis, we compared the DNA sequences of the
      EGFR gene between the primary tumor and the lymph node metastasis in 31 clinical
      samples. Only one of the patients with an EGFR mutation in the primary HNSCC
      carried the same mutation (L858R) in the lymph node metastasis. Finally, we
      explored the tumorigenic potential of the EGFR mutations that we had previously
      identified and their sensitivity to two different EGFR tyrosine kinase inhibitors
      (CL-387785, OSI-420). Ba/F3 cells transformed with mutant EGFR genes were
      sensitive to treatment with lower concentrations of CL-387785 than of OSI-420.
      These results contribute to our understanding of the genetic basis of drug
      sensitivity and will help design drugs that specifically target different
      subtypes of HNSCC.

PMID- 21953076
TI  - Comparison of ultrasonographically guided fine-needle aspiration and core needle
      biopsy in the diagnosis of parotid masses.
AB  - BACKGROUND: To retrospectively compare the accuracies of ultrasound-guided fine
      needle aspiration (USFNA) and ultrasound-guided core needle biopsy (USCNB) in the
      diagnosis of parotid masses. METHODS: A total of 171 patients (aged 17-86 years,
      mean 54 years) with parotid masses (35 malignant and 136 benign lesions)
      underwent either USFNA (n = 107) or USCNB (n = 64). The diagnostic accuracies for
      differentiating benign from malignant lesions of both examinations were compared.
      Surgical histopathology (n = 104) and clinical diagnosis (n = 67) were used to
      establish the final diagnoses. RESULTS: USCNB had a significantly higher
      sensitivity (94.1%) than USFNA (55.6%) (p < 0.05) in differentiating benign
      lesions from malignant conditions. The specificity and overall accuracy of USCNB
      were higher than those of USFNA (100% and 98.4% versus 93.3% and 86.9%,
      respectively). USCNB provided more specific diagnosis than USFNA (100% versus
      93.3%, p < 0.05). All six patients with lymphomas who underwent USCNB were
      accurately diagnosed, whereas all four patients with lymphomas who underwent
      USFNA were not. CONCLUSIONS: USCNB should be preferred to USFNA when a definite
      diagnosis of a parotid solid mass is needed.

PMID- 21953077
TI  - Violence behavior and factors associated among students of Central-West Brazil.
AB  - OBJECTIVE: To estimate the prevalence of violence among adolescents and young
      adults and to identify associated factors. METHODS: Cross-sectional study carried
      out in 2008 with systematic random sampling of 699 elementary and high school
      students enrolled in urban state schools of Barra do Garcas, Central-Western
      Brazil. A self-administered questionnaire was applied in the classrooms without
      the presence of the teacher. The outcome "violent behavior" was defined as (1)
      use of firearm or sharp instrument, and/or (2) aggression against oneself and/or
      others, and/or (3) suicide attempt. The analyzed independent variables were age,
      gender, socioeconomic status, use of alcohol, use of psychoactive drugs, sexual
      activity, and relationship between parents. Univariate analysis was conducted, as
      well as multiple regression adjusted for effect of clustering. RESULTS: Violence
      prevalence was of 18.6%, varying with age: 10.1% in the group aged 10 and 11
      years; 20.2% for those aged 12-19 years; and 4.5% in the group aged 20-21 years.
      The factors associated with violent behavior were use of alcohol (RP = 2.51,
      95%CI 1.22;5.15), use of psychoactive drugs (RP = 2.10, 95%CI 1.61;2.75), male
      gender (RP = 1.63, 95%CI 1.13;2.35) and unsatisfactory relationship between
      parents (RP = 1.64, 95%CI 1.25;2.15). CONCLUSIONS: Results indicate high
      prevalence of violence among adolescents in the age group 12-19 years, mainly
      among users of alcohol and drugs, of the male sex, from families whose parents do
      not have satisfactory relationships. Although without statistical significance in
      the final regression model, school result discrepancy and socioeconomic level
      should be considered in educational actions for prevention of violence behavior
      among students.

PMID- 21953078
TI  - Assessment of a clinical score for screening suspected pulmonary tuberculosis
      cases.
AB  - OBJECTIVE: To assess the accuracy (sensitivity) of a clinical score for
      presumptive pulmonary tuberculosis cases during screening. METHODS: Descriptive
      cross-sectional study comprising 1,365 patients attending the department of lung
      diseases at a secondary care outpatient clinic in the city of Rio de Janeiro,
      Southeastern Brazil, during 2006 and 2007. All respondents answered a
      standardized questionnaire administered by the clinic's nursing staff.
      Information on age, weight and clinical symptoms were collected. The presumptive
      diagnosis of pulmonary tuberculosis was made by summing up the scores of the data
      collected. The diagnosis of active tuberculosis was based on bacteriological
      findings and medical criteria. There were estimated sensitivity, specificity,
      positive predictive value and negative predictive value for a set prevalence, and
      95% confidence intervals for different score cutoffs. The score performance was
      assessed using the receiver operating characteristic (ROC) curve. RESULTS: For
      the diagnosis of tuberculosis, cough for more than one week and cough for more
      than three weeks showed a sensitivity of 88.2% (86.2, 90.2) and 61.1% (57.93,
      64.3), specificity 19.2% (16.6, 21.8) and 51.3% (48.1, 54.5), respectively. The
      clinical score of 8 had a sensitivity of 83.13% (77.8, 87.6), specificity of
      51.8% (48.5, 55.1), positive predictive value of 91.6% (90.0, 83.2) and negative
      predictive value of 32.9% (30.1, 35.7). CONCLUSIONS: Cough for more than three
      weeks showed low sensitivity and specificity. A highly sensitive clinical score
      can be an alternative tool for screening pulmonary tuberculosis as it allows
      early care of suspected cases and standard nursing care approach.

PMID- 21953079
TI  - Years of potential life lost and hospitalization costs associated with
      leptospirosis in Brazil.
AB  - OBJECTIVE: To estimate costs of hospitalization and years of potential life lost
      associated with leptospirosis. METHODS: Databases of the Brazilian Ministry of
      Health's information system were used to carry out probabilistic linkage of cases
      and hospitalizations leading to death by leptospirosis in 2007. Within the
      Information System for Notifiable Diseases, confirmed cases were subdivided into
      hospitalization and death. These were then linked to the Hospital Information
      System (records with primary diagnosis) and the Mortality Information System
      (underlying cause of death A27.0, A27.8, and A27.9) databases. The partial cost
      of hospitalization, deaths by disease, and years of potential life and work lost,
      were estimated. RESULTS: Most hospitalizations leading to death occurred among
      males aged 18-49 years, of white ethnicity, living in urban areas, and with
      incomplete elementary education. Years of potential life lost amounted to 6,490,
      75% of which were in the 20-49 years age group. When adjusted for the population,
      this loss represented 15 days of life/thousand persons. The ratio of years of
      potential life lost to number of deaths was on average 30 years per death. The
      estimated financial impact amounted to R$ 22.9 million in non-earned wages.
      Hospitalization costs totaled R$ 831.5 thousand. Estimated days of wages lost per
      admission period (median: 6 days) amounted to R$ 103.0 thousand. CONCLUSIONS:
      There was a high social cost in terms of years of potential life lost and partial
      hospital costs associated with leptospirosis when compared to the possibility of
      early treatment or prevention of infection, both of which could minimize the
      impact of the disease on the Brazilian population.

PMID- 21953080
TI  - The microRNA-processing enzymes: Drosha and Dicer can predict prognosis of
      nasopharyngeal carcinoma.
AB  - PURPOSE: Dysregulation of microRNA (miRNA) metabolism has been observed in a
      variety of human cancers, but the expression patterns of the enzymes responsible
      for generating miRNAs remain largely unexplored. In this study, we investigated
      the expression profiles of the two most important enzymes of the miRNA machinery,
      Drosha and Dicer, which were closely correlated with nasopharyngeal carcinoma
      (NPC) and patient survival. METHODS: Dicer and Drosha mRNA levels were detected
      by quantitative real-time reverse transcriptase polymerase chain reaction (qRT
      PCR) using 24 NPC tissues, 7 normal nasopharyngeal epithelium samples (NPE) and
      NPC cell lines. In addition, protein levels were detected by immunohistochemistry
      (IHC) using an NPC tissue microarray (TMA), which include 251 NPC and 105 NPE
      cases. For some NPC patients can not be contacted, the survival data were
      available only for 146 patients. Kaplan-Meier analysis was performed, and the chi
      square and log-rank tests were used to detect significance levels using SPSS 15.0
      software. RESULTS: The mean level of Dicer and Drosha mRNA were significantly
      down-regulated in NPC tissue specimens and cell lines when compared with
      controls. The low levels of Dicer and Drosha protein were frequently seen in NPC,
      and the low expression of Dicer and Drosha protein was significantly correlated
      with shorter progression-free survival (PFS) and overall survival (OS) of NPC
      patients. CONCLUSIONS: We observed that Drosha and Dicer expression was
      dysregulation in NPC compared with healthy control samples and was significantly
      correlated with shorter PFS and OS of NPC patients. Therefore, we hypothesise
      that the expression levels of Dicer and Drosha could be used as potential
      prognostic biomarkers for NPC.

PMID- 21953081
TI  - Conformational space exploration of Met- and Leu-enkephalin using the MOLS
      method, molecular dynamics, and Monte Carlo simulation--a comparative study.
AB  - We report here a comparative study of the molecular conformational energy
      landscape generated using the mutually orthogonal Latin squares (MOLS) method,
      molecular dynamics (MD), and Monte Carlo (MC) simulation. The MOLS method, as
      described earlier from our laboratory, uses an experimental design technique to
      rapidly and exhaustively sample the low energy conformations of a molecule. MD
      and MC simulations have been used to perform similar tasks. In the comparison
      reported here, the three methods were applied to a pair of neuropeptides, namely
      Met- and Leu-enkephalin. A set of 1500 conformations of these enkephalins were
      generated using these methods with CHARMM22 force field, and the resulting
      samples were analyzed to determine the extent and nature of coverage of the
      conformational space. The results indicate that the MOLS method samples a larger
      number of possible conformations and identifies conformations closer to the
      experimental structures than the MD and MC simulations.

PMID- 21953083
TI  - Presumptive role of 129 strain-derived Sle16 locus in rheumatoid arthritis in a
      new mouse model with Fcgamma receptor type IIb-deficient C57BL/6 genetic
      background.
AB  - OBJECTIVE: Fcgamma receptor type IIb (FcgammaRIIb) is a major negative regulator
      of B cells, and the lack of FcgammaRIIb expression has been reported to induce
      systemic lupus erythematosus (SLE) in mice of the C57BL/6 (B6) genetic
      background. The 129 strain-derived Sle16 locus on the telomeric region of
      chromosome 1 including polymorphic Fcgr2b confers the predisposition to systemic
      autoimmunity when present on the B6 background. We undertook this study to
      examine the effect of the Sle16 locus on autoimmune disease in FcgammaRIIb
      deficient B6 mice. METHODS: We established 2 lines of FcgammaRIIb-deficient B6
      congenic mouse strains (KO1 and KO2) by selective backcrossing of the originally
      constructed FcgammaRIIb-deficient mice on a hybrid (129*B6) background into a B6
      background. Although both lack FcgammaRIIb expression, the KO1 and KO2 strains
      carry different lengths of the 129 strain-derived telomeric chromosome 1 segment
      flanked to the null-mutated Fcgr2b gene; the KO1 strain carries a 129 strain
      derived ~6.3-Mb interval distal from the null-mutated Fcgr2b gene within the
      Sle16 locus, while this interval in the KO2 strain is of B6 origin. RESULTS:
      Unexpectedly, both strains failed to develop SLE; instead, the KO1 strain, but
      not the KO2 strain, spontaneously developed severe rheumatoid arthritis (RA) with
      an incidence reaching >90% at age 12 months. CONCLUSION: The current study shows
      evidence that the epistatic interaction between the Fcgr2b-null mutation and a
      polymorphic gene(s) in the 129 strain-derived interval located in the distal
      Sle16 locus contributes to RA susceptibility in a new mouse model with the B6
      genetic background, although the participation of other genetic polymorphisms
      cannot be totally excluded.

PMID- 21953084
TI  - Protective effect of RC-3095, an antagonist of the gastrin-releasing peptide
      receptor, in experimental arthritis.
AB  - OBJECTIVE: To evaluate the antiinflammatory effects of RC-3095 in 2 experimental
      models of arthritis, collagen-induced arthritis (CIA) and antigen-induced
      arthritis (AIA), and to determine the mechanisms of action involved. METHODS: RC
      3095 was administered daily to mice with CIA and mice with AIA, after induction
      of disease with methylated bovine serum albumin. Disease incidence and severity
      were assessed using a clinical index and evaluation of histologic features,
      respectively. In mice with CIA, gastrin-releasing peptide receptor (GRPR) was
      detected by immunohistochemical analysis, while in mice with AIA, migration of
      neutrophils, presence of glycosaminoglycans, and lymphocyte proliferation,
      determined using the MTT assay, were assessed. Expression of cytokines
      interleukin-17 (IL-17), IL-1beta, and tumor necrosis factor alpha (TNFalpha) was
      evaluated in all mouse knees using enzyme-linked immunosorbent assay. Treg cell
      production was assessed by flow cytometry in the joints of mice with AIA.
      RESULTS: In mice with AIA, administration of RC-3095 reduced neutrophil
      migration, mechanical hypernociception, and proteoglycan loss. These findings
      were associated with inhibition of the levels of all 3 proinflammatory cytokines,
      decreased lymphocyte proliferation, and increased Treg cell numbers. In the CIA
      model, treatment with RC-3095 led to a significant reduction in arthritis
      clinical scores and the severity of disease determined histologically. Synovial
      inflammation, synovial hyperplasia, pannus formation, and extensive erosive
      changes were all dramatically reduced in the arthritic mice treated with RC-3095.
      Furthermore, arthritic mice treated with RC-3095 showed a significant reduction
      in the concentrations of IL-17, IL-1beta, and TNFalpha, and showed a diminished
      expression of GRPR. CONCLUSION: These findings suggest that the GRP pathway has a
      significant role in chronic arthritis, and its inhibition can be explored as a
      possible therapeutic strategy in rheumatoid arthritis.

PMID- 21953085
TI  - Characterization of a new animal model for evaluation and treatment of back pain
      due to lumbar facet joint osteoarthritis.
AB  - OBJECTIVE: Osteoarthritic (OA) degeneration of the lumbar facet joints has been
      implicated in low back pain. This study was undertaken to investigate the
      biologic links between cellular and structural alterations within facet joint
      components and the development of symptomatic chronic back pain. METHODS: We
      generated an animal model of facet joint degeneration by intraarticular injection
      of monosodium iodoacetate (MIA) into facet joints (L3-L4, L4-L5, L5-L6) of
      Sprague-Dawley rats. Pain sensation due to pressure, which mimics a mechanical
      stimulus for facet joint injury, was measured using an algometer. Pain response
      was also assessed in a straight leg raising test. Cartilage alterations were
      assessed by biochemical evaluation and microfocal computed tomography (micro-CT).
      Therapeutic modulation of chronic facet joint pain with the use of various
      pharmacologic agents was investigated. RESULTS: MIA injection resulted in
      severely damaged facet joint cartilage, proteoglycan loss, and alterations of
      subchondral bone structure. Micro-CT analyses suggested that the behavioral
      hyperalgesia from facet joint degeneration was not associated with foraminal
      stenosis. The biologic and structural changes in facet joints were closely
      associated with sustained and robust chronic pain. Morphine and pregabalin
      markedly alleviated pressure hyperalgesia, while celecoxib (a selective inhibitor
      of cyclooxygenase 2 [COX-2]) produced moderate antihyperalgesic effects and the
      effect of ketorolac (an inhibitor of COX-1 and COX-2) was negligible. CONCLUSION:
      Our findings demonstrate that MIA injection provides a useful model for the study
      of OA changes in the facet joint and indicate that facet joint degeneration is a
      major cause of chronic low back pain. The treatment results suggest that classes
      of drugs that are widely used to treat OA, such as nonsteroidal antiinflammatory
      drugs, may have limited efficacy once joint destruction is complete.

PMID- 21953086
TI  - Semaphorin 3A is expressed in human osteoarthritic cartilage and antagonizes
      vascular endothelial growth factor 165-promoted chondrocyte migration: an
      implication for chondrocyte cloning.
AB  - OBJECTIVE: Vascular endothelial growth factor 165 (VEGF165) and its receptors,
      including neuropilin 1 (NRP-1), are overexpressed in human osteoarthritic (OA)
      articular cartilage, although their functional roles in the cartilage are not
      fully understood. An axon-guidance molecule, semaphorin 3A (Sema3A), which binds
      to NRP-1, acts as an antagonist of VEGF signaling in endothelial cells. The aim
      of this study was to examine the expression of Sema3A and the functions of the
      VEGF165/Sema3A/NRP-1 axis in OA cartilage. METHODS: The expression of Sema3A in
      OA and normal cartilage samples was examined by real-time polymerase chain
      reaction and immunohistochemical analyses. Functional analyses of VEGF165 and
      Sema3A were carried out using OA chondrocytes in culture. The migration activity
      of chondrocytes was examined in a monolayer wound assay. The effects of Sema3A on
      VEGF165-induced up-regulation of matrix metalloproteinases (MMPs) and
      intracellular signaling were also studied in cultured chondrocytes. RESULTS:
      Sema3A expression was significantly elevated in OA cartilage as compared to
      normal cartilage. Sema3A immunoreactivity directly correlated with the Mankin
      score and with chondrocyte cloning. VEGF165 promoted the migration of
      chondrocytes, and this activity was suppressed by VEGF receptor 2 tyrosine kinase
      inhibitors. Sema3A antagonized the chondrocyte migration promoted by VEGF165, and
      the activity was blocked by a selective inhibitor of, or small interfering RNA
      for, Sema3A. VEGF165-induced overexpression of MMPs and phosphorylation of ERK
      and focal adhesion kinase in chondrocytes were inhibited by Sema3A. CONCLUSION:
      Our findings provide the first evidence that Sema3A is overexpressed, with a
      direct correlation with cloning, in OA cartilage and that it suppresses the
      VEGF165-promoted migration of chondrocytes. Our findings also suggest that Sema3A
      plays a role in chondrocyte cloning through inhibition of cell migration in OA
      cartilage.

PMID- 21953087
TI  - Generation of human induced pluripotent stem cells from osteoarthritis patient
      derived synovial cells.
AB  - OBJECTIVE: This study was undertaken to generate and characterize human induced
      pluripotent stem cells (PSCs) from patients with osteoarthritis (OA) and to
      examine whether these cells can be developed into disease-relevant cell types for
      use in disease modeling and drug discovery. METHODS: Human synovial cells
      isolated from two 71-year-old women with advanced OA were characterized and
      reprogrammed into induced PSCs by ectopic expression of 4 transcription factors
      (Oct-4, SOX2, Klf4, and c-Myc). The pluripotency status of each induced PSC line
      was validated by comparison with human embryonic stem cells (ESCs). RESULTS: We
      found that OA patient-derived human synovial cells had human mesenchymal stem
      cell (MSC)-like characteristics, as indicated by the expression of specific
      markers, including CD14-, CD19-, CD34-, CD45-, CD44+, CD51+, CD90+, CD105+, and
      CD147+. Microarray analysis of human MSCs and human synovial cells further
      determined their unique and overlapping gene expression patterns. The
      pluripotency of established human induced PSCs was confirmed by their human ESC
      like morphology, expression of pluripotency markers, gene expression profiles,
      epigenetic status, normal karyotype, and in vitro and in vivo differentiation
      potential. The potential of human induced PSCs to differentiate into distinct
      mesenchymal cell lineages, such as osteoblasts, adipocytes, and chondrocytes, was
      further confirmed by positive expression of markers for respective cell types and
      positive staining with alizarin red S (osteoblasts), oil red O (adipocytes), or
      Alcian blue (chondrocytes). Functional chondrocyte differentiation of induced
      PSCs in pellet culture and 3-dimensional polycaprolactone scaffold culture was
      assessed by chondrocyte self-assembly and histology. CONCLUSION: Our findings
      indicate that patient-derived synovial cells are an attractive source of MSCs as
      well as induced PSCs and have the potential to advance cartilage tissue
      engineering and cell-based models of cartilage defects.

PMID- 21953088
TI  - High incidence of potentially virus-induced malignancies in systemic lupus
      erythematosus: a long-term followup study in a Danish cohort.
AB  - OBJECTIVE: Patients with systemic lupus erythematosus (SLE) seem to experience an
      increased prevalence of oncogenic virus infections. The aim of the present study
      was to investigate whether SLE patients have an increased risk of virus
      associated malignancies, defined as malignancies potentially caused by virus
      infection. METHODS: A hospital-based cohort of 576 SLE patients was linked to the
      Danish Cancer Registry. The cohort was followed up for malignancies from the date
      of SLE diagnosis, and standardized incidence ratios (SIRs) were calculated for
      various forms of cancer. RESULTS: The median duration of followup was 13.2 years.
      Compared to the general population, the patients experienced an increased overall
      risk of cancer (SIR 1.6 [95% confidence interval (95% CI)] 1.2-2.0). We observed
      an increased risk of virus-associated cancers combined (SIR 2.9 [95% CI 2.0
      4.1]). Among human papillomavirus (HPV)-associated malignant and premalignant
      conditions, high risk was found for anal cancer (SIR 26.9 [95% CI 8.7-83.4]),
      vaginal/vulvar cancer (SIR 9.1 [95% CI 2.3-36.5]), epithelial dysplasia/carcinoma
      in situ of the uterine cervix (SIR 1.8 [95% CI 1.2-2.7]), and nonmelanoma skin
      cancer (SIR 2.0 [95% CI 1.2-3.6]). Increased SIRs were also found for other
      potentially virus-induced cancer types (liver cancer SIR 9.9 [95% CI 2.5-39.8],
      bladder cancer SIR 3.6 [95% CI 1.4-9.7], and non-Hodgkin's lymphoma SIR 5.0 [95%
      CI 1.9-13.3]). CONCLUSION: The patients in this SLE cohort experienced an
      increased risk of HPV-associated tumors and other potentially virus-induced
      cancers during long-term followup. Our findings call for clinical alertness to
      oncogenic virus infections in SLE patients.

PMID- 21953089
TI  - Incidence of nontraumatic osteonecrosis of the femoral head in the Japanese
      population.
AB  - OBJECTIVE: To estimate the incidence rate of nontraumatic osteonecrosis of the
      femoral head (ONFH) in the Japanese population. METHODS: A survey was conducted
      to ascertain newly identified patients with nontraumatic ONFH in the Specified
      Disease Treatment Research Program of Fukuoka Prefecture (population 5 million)
      between 1999 and 2008. Distributions of age and sex in this population were
      investigated. Crude incidence rates of nontraumatic ONFH were calculated, and age
      adjusted incidence rates were estimated by adjusting the crude values against
      those for the Japanese standard population in each year. RESULTS: In Fukuoka
      Prefecture, 1,244 newly identified patients with nontraumatic ONFH were recruited
      into the Japanese subsidy program over the span of 10 years. The ratio of men to
      women was 1.6, comprising 758 men (61%; mean age 48 years) and 486 women (39%;
      mean age 56 years). The crude incidence rate of nontraumatic ONFH in the 10-year
      period was 2.58 cases per 100,000 person-years (range 1.54-3.66). The mean age
      adjusted incidence rate was 2.51 cases per 100,000 person-years. CONCLUSION: This
      study showed that the incidence rate of nontraumatic ONFH was 2.51 cases per
      100,000 person-years in the Japanese population.

PMID- 21953091
TI  - Expression of ER stress and autophagy-related molecules in human non-small cell
      lung cancer and premalignant lesions.
AB  - Stress that impairs endoplasmic reticulum (ER) function leads to an accumulation
      of unfolded or misfolded proteins in the ER (ER stress). Autophagy is a lysosomal
      pathway involved in the turnover of cellular macromolecules and organelles, which
      emerging data indicate that ER stress is also a potent inducer of autophagy. ER
      stress and autophagy are involved in human cancer. We examined the expression of
      ER stress-related proteins [GRP78 and C/EBP homologous protein (CHOP)] and
      autophagic proteins (Beclin-1 and LC3) in non-small cell lung carcinomas
      (NSCLCs), bronchioloalveolar carcinomas (BACs) and atypical adenomatous
      hyperplasias (AAHs) to understand their role in the NSCLC pathogenesis. The
      expression of GRP78 and CHOP, Beclin-1 and LC3 were analyzed using
      immunohistochemistry on tissue sections from 133 NSCLC (69 squamous cell
      carcinomas, 56 adenocarcinomas (AC) and eight other NSCLCs), 21 BAC and 9 AAH.
      Expression of GRP78 and Beclin-1 was correlated with low tumor stage (p < 0.001
      and p = 0.019, respectively) and longer survival (p = 0.007 and p <0.001,
      respectively) by Kaplan-Meier analysis. However, CHOP was correlated with high
      tumor stage (p = 0.038) and shorter survival (p = 0.012). Expression of GRP78 and
      Beclin-1 was positively correlated (p = 0.006). Our study showed that the
      expression of GRP78, CHOP, Beclin-1 and LC3 in lung cancer and its relation with
      clinicopathologic factors and patients survival. These results suggest that
      GRP78, CHOP and Beclin-1 may play an important role in tumorigenesis of lung AC
      and may serve as new prognostic indicators for outcome of the patients with
      NSCLC.

PMID- 21953092
TI  - Target-decoy approach and false discovery rate: when things may go wrong.
AB  - The target-decoy approach (TDA) has done the field of proteomics a great service
      by filling in the need to estimate the false discovery rates (FDR) of peptide
      identifications. While TDA is often viewed as a universal solution to the problem
      of FDR evaluation, we argue that the time has come to critically re-examine TDA
      and to acknowledge not only its merits but also its demerits. We demonstrate that
      some popular MS/MS search tools are not TDA-compliant and that it is easy to
      develop a non-TDA compliant tool that outperforms all TDA-compliant tools. Since
      the distinction between TDA-compliant and non-TDA compliant tools remains
      elusive, we are concerned about a possible proliferation of non-TDA-compliant
      tools in the future (developed with the best intentions). We are also concerned
      that estimation of the FDR by TDA awkwardly depends on a virtual coin toss and
      argue that it is important to take the coin toss factor out of our estimation of
      the FDR. Since computing FDR via TDA suffers from various restrictions, we argue
      that TDA is not needed when accurate p-values of individual Peptide-Spectrum
      Matches are available.

PMID- 21953093
TI  - Sequence scrambling in shotgun proteomics is negligible.
AB  - Analysis of 15,897 low-energy (CAD) and 10,878 higher-energy (HCD) collisional
      dissociation mass spectra of doubly protonated tryptic peptides taken with high
      resolution revealed that the rate of sequence scrambling due to b-ion cyclization
      is negligible (<1%) and can be safely ignored as a possible source of erroneous
      sequence assignment in shotgun proteomics. On the other hand, there is
      significant presence of normal (non-scrambled) internal fragments in HCD, which
      should be taken into account by MS/MS search engines.

PMID- 21953094
TI  - Initial experimental characterization of a new ultra-high resolution FTICR cell
      with dynamic harmonization.
AB  - A new Fourier transform ion cyclotron resonance (FTICR) cell based on completely
      new principles of formation of the effective electric potential distribution in
      Penning type traps, Boldin and Nikolaev (Proceedings of the 58th ASMS Conference,
      2010), Boldin and Nikolaev (Rapid Commun Mass Spectrom 25:122-126, 2011) is
      constructed and tested experimentally. Its operation is based on the concept of
      electric potential space-averaging via charged particle cyclotron motion. Such an
      averaging process permits an effective electric force distribution in the entire
      volume of a cylindrical Penning trap to be equal to its distribution in the field
      created by hyperbolic electrodes in an ideal Penning trap. The excitation and
      detection electrodes of this new cell are shaped for generating a quadratic
      dependence on axial coordinates of an averaged (along cyclotron motion orbit)
      electric potential at any radius of the cyclotron motion. These electrodes
      together with the trapping segments form a cylindrical surface like in a
      conventional cylindrical cell. In excitation mode this cell being elongated
      behaves almost like an open cylindrical cell of the same length. It is more
      effective in ion motion harmonization at larger cyclotron radii than a Gabrielse
      et al.-type (Int J Mass Spectrom Ion Processes 88:319-332, 1989) cylindrical cell
      with four compensation sections. A mass resolving power of more than twenty
      millions of reserpine (m/z 609) and more than one million of highly charged BSA
      molecular ions (m/z 1357) has been obtained in a 7T magnetic field.

PMID- 21953095
TI  - A mass-selective variable-temperature drift tube ion mobility-mass spectrometer
      for temperature dependent ion mobility studies.
AB  - A hybrid ion mobility-mass spectrometer (IM-MS) incorporating a variable
      temperature (80-400 K) drift tube is presented. The instrument utilizes an
      electron ionization (EI) source for fundamental small molecule studies. Ions are
      transferred to the IM-MS analyzer stages through a quadrupole, which can operate
      in either broad transmission or mass-selective mode. Ion beam modulation for the
      ion mobility experiment is accomplished by an electronic shutter gate. The
      variable-temperature ion mobility spectrometer consists of a 30.2 cm uniform
      field drift tube enclosed within a thermal envelope. Subambient temperatures down
      to 80 K are achievable through cryogenic cooling with liquid nitrogen, while
      elevated temperatures can be accessed through resistive heating of the envelope.
      Mobility separated ions are mass analyzed by an orthogonal time-of-flight (TOF)
      mass spectrometer. This report describes the technological considerations for
      operating the instrument at variable temperature, and preliminary results are
      presented for IM-MS analysis of several small mass ions. Specifically, mobility
      separations of benzene fragment ions generated by EI are used to illustrate
      significantly improved (greater than 50%) ion mobility resolution at low
      temperatures resulting from decreased diffusional broadening. Preliminary results
      on the separation of long-lived electronic states of Ti(+) formed by EI of
      TiCl(4) and hydration reactions of Ti(+) with residual water are presented.

PMID- 21953096
TI  - Separation and classification of lipids using differential ion mobility
      spectrometry.
AB  - Correlations between the dimensions of a 2-D separation create trend lines that
      depend on structural or chemical characteristics of the compound class and thus
      facilitate classification of unknowns. This broadly applies to conventional ion
      mobility spectrometry (IMS)/mass spectrometry (MS), where the major biomolecular
      classes (e.g., lipids, peptides, nucleotides) occupy different trend line
      domains. However, strong correlation between the IMS and MS separations for ions
      of same charge has impeded finer distinctions. Differential IMS (or FAIMS) is
      generally less correlated to MS and thus could separate those domains better. We
      report the first observation of chemical class separation by trend lines using
      FAIMS, here for lipids. For lipids, FAIMS is indeed more independent of MS than
      conventional IMS, and subclasses (such as phospho-, glycero-, or sphingolipids)
      form distinct, often non-overlapping domains. Even finer categories with
      different functional groups or degrees of unsaturation are often separated. As
      expected, resolution improves in He-rich gases: at 70% He, glycerolipid isomers
      with different fatty acid positions can be resolved. These results open the door
      for application of FAIMS to lipids, particularly in shotgun lipidomics and
      targeted analyses of bioactive lipids.

PMID- 21953098
TI  - Liquid microjunction surface sampling probe fluid dynamics: computational and
      experimental analysis of coaxial intercapillary positioning effects on sample
      manipulation.
AB  - A coaxial geometry liquid microjunction surface sampling probe (LMJ-SSP) enables
      direct extraction of analytes from surfaces for subsequent analysis by techniques
      like mass spectrometry. Solution dynamics at the probe-to-sample surface
      interface in the LMJ-SSP has been suspected to influence sampling efficiency and
      dispersion but has not been rigorously investigated. The effect on flow dynamics
      and analyte transport to the mass spectrometer caused by coaxial retraction of
      the inner and outer capillaries from each other and the surface during sampling
      with a LMJ-SSP was investigated using computational fluid dynamics and
      experimentation. A transparent LMJ-SSP was constructed to provide the means for
      visual observation of the dynamics of the surface sampling process. Visual
      observation, computational fluid dynamics (CFD) analysis, and experimental
      results revealed that inner capillary axial retraction from the flush position
      relative to the outer capillary transitioned the probe from a continuous sampling
      and injection mode through an intermediate regime to sample plug formation mode
      caused by eddy currents at the sampling end of the probe. The potential for
      analytical implementation of these newly discovered probe operational modes is
      discussed.

PMID- 21953099
TI  - What happens to hydrophobic interactions during transfer from the solution to the
      gas phase? The case of electrospray-based soft ionization methods.
AB  - The disappearance of the hydrophobic effect in the gas phase due to the absence
      of an aqueous surrounding raises a long-standing question: can noncovalent
      complexes that are exclusively bound by hydrophobic interactions in solution be
      preserved in the gas phase? Some reports of successful detection by mass
      spectrometry of complexes largely stabilized by hydrophobic effect are
      questionable by the presence of electrostatic forces that hold them together in
      the gas phase. Here, we report on the MS-based analysis of model supramolecular
      complexes with a purely hydrophobic association in solution, beta-cyclodextrin,
      and synthetic adamantyl-containing ligands with several binding sites. The
      stability of these complexes in the gas phase is investigated by quantum chemical
      methods (DFT-M06). Compared with the free interaction partners, the inclusion
      complex between beta-cyclodextrin and adamantyl-containing ligand is shown to be
      stabilized in the gas phase by DeltaG = 9.6 kcal mol(-1). The host-guest
      association is mainly enthalpy-driven due to strong dispersion interactions
      caused by a large nonpolar interface and a high steric complementarity of the
      binding partners. Interference from other types of noncovalent binding forces is
      virtually absent. The complexes are successfully detected via electrospray
      ionization mass spectrometry, although a high dissociation yield is also
      observed. We attribute this pronounced dissociation of the complexes to the
      collisional activation of ions in the atmospheric interface of mass spectrometer.
      The comparison of several electrospray-based ionization methods reveals that cold
      spray ionization provides the softest ion generation conditions for these
      complexes.

PMID- 21953100
TI  - Protein conformation and supercharging with DMSO from aqueous solution.
AB  - The efficacy of dimethyl sulfoxide (DMSO) as a supercharging reagent for protein
      ions formed by electrospray ionization from aqueous solution and the mechanism
      for supercharging were investigated. Addition of small amounts of DMSO to aqueous
      solutions containing hen egg white lysozyme or equine myoglobin results in a
      lowering of charge, whereas a significant increase in charge occurs at higher
      concentrations. Results from both near-UV circular dichroism spectroscopy and
      solution-phase hydrogen/deuterium exchange mass spectrometry indicate that DMSO
      causes a compaction of the native structure of these proteins at low
      concentration, but significant unfolding occurs at ~63% and ~43% DMSO for
      lysozyme and myoglobin, respectively. The DMSO concentrations required to
      denature these two proteins in bulk solution are ~3-5 times higher than the
      concentrations required for the onset of supercharging, consistent with a
      significantly increased concentration of this high boiling point supercharging
      reagent in the ESI droplet as preferential evaporation of water occurs. DMSO is
      slightly more basic than m-nitrobenzyl alcohol and sulfolane, two other
      supercharging reagents, based on calculated proton affinity and gas-phase
      basicity values both at the B3LYP and MP2 levels of theory, and all three of
      these supercharging reagents are significantly more basic than water. These
      results provide additional evidence that the origin of supercharging from aqueous
      solution is the result of chemical and/or thermal denaturation that occurs in the
      ESI droplet as the concentration of these supercharging reagents increases, and
      that proton transfer reactivity does not play a significant role in the charge
      enhancement observed.

PMID- 21953101
TI  - Gas-phase ions of human hemoglobin A, F, and S.
AB  - Hemoglobin (Hb) (alpha(2)beta(2)) is a tetrameric protein-protein complex.
      Collision cross sections, hydrogen exchange levels, and tandem mass spectrometry
      have been used to investigate the properties of gas-phase monomer, dimer, and
      tetramer ions of adult human hemoglobin (Hb A, alpha(2)beta(2)), and two variant
      hemoglobins: fetal hemoglobin (Hb F, alpha(2)gamma(2)) and sickle hemoglobin (Hb
      S, alpha(2)beta(2), E6V[beta]). All three proteins give similar mass spectra.
      Monomers of Hb S and Hb F have similar cross sections, ca. 10% greater than those
      of Hb A. Cross sections of dimer ions of Hb S are 11% greater than those of Hb A
      and 6% greater than those of Hb F. Tetramers of Hb S are 13% larger than
      tetramers of Hb A or Hb F. Monomers and dimers of all three Hb have similar
      hydrogen-deuterium exchange (HDX) levels. Tetramers of Hb S exchange 16% more
      hydrogens than Hb A and Hb F. In tandem mass spectrometry, monomers of Hb S and
      Hb F require ca. 10% greater internal energy for heme loss than Hb A. Dimers
      (+11) of Hb A and Hb S dissociate to monomers with asymmetrical charge division;
      dimers of Hb F (+11) dissociate with nearly equal charge division. Tetramer ions
      dissociate to monomers and trimers, unlike solution Hb, which dissociates to
      dimers. The most stable dimers are from Hb S; the most stable tetramers from Hb
      F. The results with Hb S show that a single mutation in the beta chain can change
      the physical properties of this gas-phase protein-protein complex.

PMID- 21953102
TI  - Diagnostic NH and OH vibrations for oxazolone and diketopiperazine structures: b2
      from protonated triglycine.
AB  - We present infrared multiple photon dissociation (IRMPD) spectra in the hydrogen
      stretching region of the simplest b fragment, b(2) from protonated triglycine,
      contrasted to that of protonated cyclo(Gly-Gly). Both spectra confirm the
      presence of intense, diagnostic vibrations linked to the site of proton
      attachment. Protonated cyclo(Gly-Gly) serves as a reference spectrum for the
      diketopiperazine structure, showing a diagnostic O-H(+) stretch of the protonated
      carbonyl group at 3585 cm(-1). Conversely, b(2) from protonated triglycine
      exhibits a strong band at 3345 cm(-1), associated with the N-H stretching mode of
      the protonated oxazolone ring structure. Other weaker N-H stretches can also be
      discerned, such as the amino NH(2) and amide NH bands. These results demonstrate
      the usefulness of the hydrogen stretching region, and hence benchtop optical
      parametric oscillator/amplifier (OPO/A) set-ups, in making structural assignments
      of product ions in collision-induced dissociation (CID) of peptides.

PMID- 21953103
TI  - Integration of high accuracy N-terminus identification in peptide sequencing and
      comparative protein analysis via isothiocyanate-based isotope labeling reagent
      with ESI ion-trap TOF MS.
AB  - A multifunctional isothiocyanate-based isotope labeling reagent, [d (0)]-/[d (6)]
      4,6-dimethoxy pyrimidine-2-isothiocyanate (DMPITC), has been developed for
      accurate N-terminus identification in peptide sequencing and comparative protein
      analysis by ESI Ion-trap TOF mass spectrometry. In contrast with the conventional
      labeling reagent phenyl isothiocyanate (PITC), DMPITC showed more desirable
      properties such as rapid labeling, sensitivity enhancement, and facilitating
      peptide sequencing. More significantly, DMPITC-based labeling strategy possessed
      the capacity of higher reliable N-terminus identification owning to the high
      yield b(1) ion combined with the isotope validation of 6 Da. Meanwhile, it also
      showed potential in differentiating isomeric residues of leucine and isoleucine
      at N-terminus on the basis of the relative abundance ratios between the fragment
      ions of their respective b(1) ions. The strategy not only allows accurate
      interpretation for peptide but also ensures rapid and sensitive comparative
      analysis for protein by direct MS analysis. Using trypsin-digested bovine serum
      albumin (BSA), both peptide N-terminus identification and quantitative analysis
      were accomplished with high accuracy, efficiency, and reproducibility. The
      application of DMPITC-based labeling strategy is expected to serve as a promising
      tool for proteome research.

PMID- 21953104
TI  - Second order rate constants of donor-strand exchange reveal individual amino acid
      residues important in determining the subunit specificity of pilus biogenesis.
AB  - P pili are hair-like adhesive structures that are assembled on the outer membrane
      (OM) of uropathogenic Escherichia coli by the chaperone-usher pathway. In this
      pathway, chaperone-subunit complexes are formed in the periplasm and targeted to
      an OM assembly platform, the usher. Pilus subunits display a large groove caused
      by a missing beta-strand which, in the chaperone-subunit complex, is provided by
      the chaperone. At the usher, pilus subunits are assembled in a mechanism termed
      "donor-strand exchange (DSE)" whereby the beta-strand provided by the chaperone
      is exchanged by the incoming subunit's N-terminal extension (Nte). This occurs in
      a zip-in-zip-out fashion, starting with a defined residue, P5, in the Nte
      inserting into a defined site in the groove, the P5 pocket. Here, electrospray
      ionization-mass spectrometry (ESI-MS) has been used to measure DSE rates in
      vitro. Second order rate constants between the chaperone-subunit complex and a
      range of Nte peptides substituted at different residues confirmed the importance
      of the P5 residue of the Nte in determining the rate of DSE. In addition,
      residues either side of the P5 residue (P5 + 1 and P5 - 1), the side-chains of
      which are directed away from the subunit groove, also modulate the rates of DSE,
      most likely by aiding the docking of the Nte into the P5 pocket on the accepting
      subunit prior to DSE. The ESI-MS approach developed is applicable to the
      measurement of rates of DSE in pilus biogenesis in general and demonstrates the
      scope of ESI-MS in determining biomolecular processes in molecular detail.

PMID- 21953105
TI  - Calpha-C bond cleavage of the peptide backbone in MALDI in-source decay using
      salicylic acid derivative matrices.
AB  - The use of 5-formylsalicylic acid (5-FSA) and 5-nitrosalicylic acid (5-NSA) as
      novel matrices for in-source decay (ISD) of peptides in matrix-assisted laser
      desorption/ionization (MALDI) is described. The use of 5-FSA and 5-NSA generated
      a- and x-series ions accompanied by oxidized peptides [M - 2 H + H](+). The
      preferential formation of a- and x-series ions was found to be dependent on the
      hydrogen-accepting ability of matrix. The hydrogen-accepting ability estimated
      from the ratio of signal intensity of oxidized product [M - 2 H + H](+) to that
      of non-oxidized protonated molecule [M + H](+) of peptide was of the order 5-NSA
      > 5-FSA > 5-aminosalicylic acid (5-ASA) ? 2,5-dihydroxyl benzoic acid (2,5-DHB) ?
      0. The results suggest that the hydrogen transfer reaction from peptide to 5-FSA
      and 5-NSA occurs during the MALDI-ISD processes. The hydrogen abstraction from
      peptides results in the formation of oxidized peptides containing a radical site
      on the amide nitrogen with subsequent radical-induced cleavage at the Calpha-C
      bond, leading to the formation of a- and x-series ions. The most significant
      feature of MALDI-ISD with 5-FSA and 5-NSA is the specific cleavage of the Calpha
      C bond of the peptide backbone without degradation of side-chain and post
      translational modifications (PTM). The matrix provides a useful complementary
      method to conventional MALDI-ISD for amino acid sequencing and site localization
      of PTMs in peptides.

PMID- 21953106
TI  - The role of nebulizer gas flow in electrosonic spray ionization (ESSI).
AB  - In this work, we investigated the role of the nebulizer gas flow in electrosonic
      spray ionization (ESSI), by systematically studying the relation between the flow
      and the ion signals of proteins, such as cytochrome c and holomyoglobin using
      ESSI-mass spectrometry (MS). When a neutral solution was delivered with a small
      sample flow rate (<=5 MUL/min), no obvious transition from electrospray
      ionization (ESI) to ESSI was found as the gas velocity varies from subsonic to
      supersonic speed. Droplets mostly experienced acceleration instead of breakup by
      the high-speed nebulizer gas. On the contrary, using particular experimental
      conditions, such as an acidic solution or high sample flow rate (>=200 MUL/min),
      more folded protein ions appear to be kept in droplets of diminishing size due to
      breakup by the high-speed nebulizer gas in ESSI compared with ESI. Theoretical
      analyses and numerical simulations were also performed to explain the observed
      phenomena. These systematic studies clarify the ionization mechanism of ESSI and
      provide valuable insight for optimizing ESSI and other popular pneumatically
      assisted electrospray ionization methods for future applications.

PMID- 21953107
TI  - A nano-chip-LC/MSn based strategy for characterization of modified nucleosides
      using reduced porous graphitic carbon as a stationary phase.
AB  - LC/MS analysis of ribonucleosides is traditionally performed by reverse phase
      chromatography on silica based C18 type stationary phases using MS compatible
      buffers and methanol or acetonitrile gradients. Due to the hydrophilic and polar
      nature of nucleosides, down-scaling C18 analytical methods to a two-column nano
      flow setup is inherently difficult. We present a nano-chip LC/MS ion-trap
      strategy for routine characterization of RNA nucleosides in the fmol range.
      Nucleosides were analyzed in positive ion mode by reverse phase chromatography
      using a 75 MU * 150 mm, 5 MU particle porous graphitic carbon (PGC) chip with an
      integrated 9 mm, 160 nL trapping column. Nucleosides were separated using a
      formic acid/acetonitrile gradient. The method was able to separate isobaric
      nucleosides as well as nucleosides with isotopic overlap to allow unambiguous MS(
      n ) identification on a low resolution ion-trap. Synthesis of 5-hydroxycytidine
      (oh(5)C) was achieved from 5-hydroxyuracil in a novel three-step enzymatic
      process. When operated in its native state using formic acid/acetonitrile, PGC
      oxidized oh(5)C to its corresponding glycols and formic acid conjugates.
      Reduction of the PGC stationary phase was achieved by flushing the chip with 2.5
      mM oxalic acid and adding 1 mM oxalic acid to the online solvents. Analyzed under
      reduced chromatographic conditions oh(5)C was readily identified by its MH(+) m/z
      260 and MS(n) fragmentation pattern. This investigation is, to our knowledge, the
      first instance where oxalic acid has been used as an online reducing agent for
      LC/MS. The method was subsequently used for complete characterization of
      nucleosides found in tRNAs using both PGC and C18 chips.

PMID- 21953108
TI  - Isomeric distinction of small oligosaccharides: a bottom-up approach using the
      kinetic method.
AB  - Isomeric distinction of di- and tri-saccharides could be efficiently achieved by
      using data previously obtained while performing experiments aimed at
      discriminating monosaccharides using trimeric ion dissociation with data analysis
      by the kinetic method. This study shows that effects observed for lower
      homologues when one of the partners is changed in the metal/reference system
      (typically a transition metal divalent cation associated to amino acids) can be
      extrapolated to upper homologues, at least for the tested analyte series. Systems
      allowing galactose, glucose, and fructose distinction were used as starting
      conditions to resolve cellobiose, lactose, maltose, and saccharose disaccharides.
      When a unique dissociation reaction was observed from the trimeric clusters, a
      new reference was selected based on its propensity to favor the analyte or the
      reference release, as revealed from monosaccharide experiments, depending on the
      desired effect. The same approach could be implemented from data obtained for
      disaccharides to select efficient metal/reference systems to distinguish
      cellotriose, isomaltotriose, maltotriose, and panose trisaccharides. As a result,
      method optimization is greatly improved due to an enhanced rationalization of the
      search for discriminant systems. While 40 systems had to be tested for
      monosaccharides, by screening five transition metals and eight amino acids, the
      proposed approach allowed efficient metal/reference systems to be found for
      disaccharides after testing 18 combinations; then, only four systems had to be
      scrutinized to achieve trisaccharide distinction. Accurate quantitative analyses
      could be performed in binary mixtures using three-point calibration curves to
      correct for competition effects between analytes for the formation of the
      trimeric clusters.

PMID- 21953109
TI  - Gas phase reactions of 1,3,5-triazine: proton transfer, hydride transfer, and
      anionic sigma-adduct formation.
AB  - The gas phase reactivity of 1,3,5-triazine with several oxyanions and carbanions,
      as well as amide, was evaluated using a flowing afterglow-selected ion flow tube
      mass spectrometer. Isotopic labeling, H/D exchange, and collision induced
      dissociation experiments were conducted to facilitate the interpretation of
      structures and fragmentation processes. A multi-step (-> HCN + HC(2)N (2) (-) ->
      CN(-) + 2 HCN) and/or single-step (-> CN(-) + 2 HCN) ring-opening collision
      induced fragmentation process appears to exist for 1,3,5-triazinide. In addition
      to proton and hydride transfer reactions, the data indicate a competitive
      nucleophilic aromatic addition pathway (S(N)Ar) over a wide range of relative gas
      phase acidities to form strong anionic sigma-adducts (Meisenheimer complexes).
      The significant hydride acceptor properties and stability of the anionic sigma
      adducts are rationalized by extremely electrophilic carbon centers and symmetric
      charge delocalization at the electron-withdrawing nitrogen positions. The types
      of anion-arene binding motifs and their influence on reaction pathways are
      discussed.

PMID- 21953110
TI  - Direct laser desorption ionization of endogenous and exogenous compounds from
      insect cuticles: practical and methodologic aspects.
AB  - We recently demonstrated that ultraviolet laser desorption ionization orthogonal
      time-of-flight mass spectrometry (UV-LDI o-TOF MS) could be used for the matrix
      free analysis of cuticular lipids (unsaturated aliphatic and oxygen-containing
      hydrocarbons and triacylglycerides) directly from individual Drosophila
      melanogaster fruit flies (Yew, J. Y.; Dreisewerd, K.; Luftmann, H.; Pohlentz, G.;
      Kravitz, E. A., Curr. Biol. 2009, 19, 1245-1254). In this report, we show that
      the cuticular hydrocarbon, fatty acid, and triglyceride profiles of other insects
      and spiders can also be directly analyzed from intact body parts. Mandibular
      pheromones from the jaw of a queen honey bee are provided as one example. In
      addition, we describe analytical features and examine mechanisms underlying the
      methodology. Molecular ions of lipids can be generated by direct UV-LDI when non
      endogenous compounds are applied to insect wings or other body parts. Current
      sensitivity limits are in the 10 pmol range. We show also the dependence of ion
      signal intensity on collisional cooling gas pressure in the ion source, laser
      wavelength (varied between 280-380 nm and set to 2.94 MUm for infrared LDI), and
      laser pulse energy.

PMID- 21953112
TI  - Efficient analysis of non-polar environmental contaminants by MALDI-TOF MS with
      graphene as matrix.
AB  - In this Application Note, we describe, for the first time, the rapid analysis of
      hydrophobic compounds present in environmental contaminants, which includes
      polycyclic aromatic hydrocarbons (PAHs) and estrogen, by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with the
      use of graphene as matrix. MALDI-TOF MS with conventional matrix has limitations
      in analyzing low-polarity compounds owing to their difficulty in ionization. We
      demonstrate that compared with conventional matrix, graphene displays higher
      desorption/ionization efficiencies for PAHs, and no fragment ions are observed.
      The method also holds potential in quantitative analysis. In addition, the
      ionization signal increases with the increasing number of benzene rings in the
      PAHs, suggesting that graphene binds to PAHs via pi-pi stacking interactions.
      Furthermore, graphene as adsorbent for solid-phase extraction of coronene from
      river water sample displays good performance with a detection limit of 10(-7) M.
      This work provides a novel and convenient method for analyzing low-polarity
      environmental contaminants by MALDI-TOF MS.

PMID- 21953111
TI  - Direct detection of pharmaceuticals and personal care products from aqueous
      samples with thermally-assisted desorption electrospray ionization mass
      spectrometry.
AB  - An ambient mass spectrometric method based on desorption electrospray ionization
      (DESI) has been developed to allow rapid, direct analysis of contaminated water
      samples, and the technique was evaluated through analysis of a wide array of
      pharmaceutical and personal care product (PPCP) contaminants. Incorporating
      direct infusion of aqueous sample and thermal assistance into the source design
      has allowed low ppt detection limits for the target analytes in drinking water
      matrices. With this methodology, mass spectral information can be collected in
      less than 1 min, consuming ~100 MUL of total sample. Quantitative ability was
      also demonstrated without the use of an internal standard, yielding decent
      linearity and reproducibility. Initial results suggest that this source
      configuration is resistant to carryover effects and robust towards multi
      component samples. The rapid, continuous analysis afforded by this method offers
      advantages in terms of sample analysis time and throughput over traditional
      hyphenated mass spectrometric techniques.

PMID- 21953113
TI  - The transcription factor c-Jun protects against sustained hepatic endoplasmic
      reticulum stress thereby promoting hepatocyte survival.
AB  - Endoplasmic reticulum (ER) stress due to accumulation of hepatoviral or misfolded
      proteins is increasingly recognized as an important step in the pathogenesis of
      inflammatory, toxic, and metabolic liver diseases. ER stress results in the
      activation of several intracellular signaling pathways including Jun N-terminal
      kinase (JNK). The AP-1 (activating protein 1) transcription factor c-Jun is a
      prototypic JNK target and important regulator of hepatocyte survival,
      proliferation, and liver tumorigenesis. Because the functions of c-Jun during the
      ER stress response are poorly understood, we addressed this issue in primary
      hepatocytes and livers of hepatocyte-specific c-Jun knockout mice. ER stress was
      induced pharmacologically in vitro and in vivo and resulted in a rapid and robust
      induction of c-Jun protein expression. Interestingly, ER-stressed hepatocytes
      lacking c-Jun displayed massive cytoplasmic vacuolization due to ER distension.
      This phenotype correlated with exacerbated and sustained activation of canonical
      ER stress signaling pathways. Moreover, sustained ER stress in hepatocytes
      lacking c-Jun resulted in increased cell damage and apoptosis. ER stress is also
      a strong inducer of macroautophagy, a cell-protective mechanism of self
      degradation of cytoplasmic components and organelles. Interestingly,
      autophagosome numbers in response to ER stress were reduced in hepatocytes
      lacking c-Jun. To further validate these findings, macroautophagy was inhibited
      chemically in ER-stressed wildtype hepatocytes, which resulted in cytoplasmic
      vacuolization and increased cell damage closely resembling the phenotypes
      observed in c-Jun-deficient cells. CONCLUSION: Our findings indicate that c-Jun
      protects hepatocytes against excessive activation of the ER stress response and
      subsequent cell death and provide evidence that c-Jun functionally links ER
      stress responses and macroautophagy.

PMID- 21953114
TI  - The influence of light at night exposure on melatonin levels among Canadian
      rotating shift nurses.
AB  - BACKGROUND: Shift work has been identified as a risk factor for several cancer
      sites in recent years, with melatonin as a potential intermediate on the proposed
      causal pathway. This study examined the influence of nighttime light exposure on
      melatonin levels among 123 rotating shift nurses. METHODS: Nurses working a
      rotating shift schedule (two 12-hour days, two 12-hour nights, and five days off)
      were recruited and participated on a day and night shift in both the summer and
      winter seasons. Over each 48-hour study period, nurses wore a light data logger
      and provided two urine and four saliva samples. RESULTS: Saliva measurements
      showed that the pattern of melatonin production did not differ between day and
      night shifts. Mean light exposure was significantly higher (P < 0.0001) when
      nurses were working at night, although peak melatonin levels (P = 0.65) and the
      daily change in melatonin levels (P = 0.80) were similar across day/night shifts.
      Multivariate analysis did not show an association between light exposure and
      melatonin levels when data from both shifts was combined; however, when data from
      the night shift was considered alone, a statistically significant inverse
      relationship between light and change in melatonin was observed (P = 0.04).
      CONCLUSION: These results show that light exposure does not seem to be strongly
      related to reduced melatonin production among nurses on this rapidly rotating
      shift schedule. IMPACT: Future research considering more extreme shift patterns
      or brighter lighting conditions could further clarify the relationship between
      light exposure and melatonin production in observational settings.

PMID- 21953115
TI  - Cancer fatalism and poor self-rated health mediate the association between
      socioeconomic status and uptake of colorectal cancer screening in England.
AB  - BACKGROUND: Little is known about the psychological predictors of colorectal
      screening uptake in England and mediators of associations between uptake and
      socioeconomic status (SES). This study tested the hypotheses that although higher
      threat and efficacy beliefs, lower cancer fatalism, lower depression, and better
      self-rated health would predict higher screening uptake, only efficacy beliefs,
      fatalism, depression, and self-rated health would mediate associations between
      uptake and SES. METHODS: Data from 529 adults aged 60 to 69 who had completed a
      postal survey in 2005-2006 were linked with data on fecal occult blood test
      (FOBt) uptake recorded at the screening "hub" following its introduction in 2007,
      resulting in a prospective study. RESULTS: Screening uptake was 56% and was
      higher among people with higher SES, better self-rated health, higher self
      efficacy beliefs, and lower cancer fatalism in univariate analyses. Path analysis
      on participants with complete data (n = 515) showed that both better self-rated
      health and lower cancer fatalism were directly associated with higher uptake of
      FOBt screening and significantly mediated pathways from SES to uptake. Lower
      depression only had an indirect effect on uptake through better self-rated
      health. Efficacy beliefs did not mediate the relationship between SES and uptake.
      CONCLUSION: SES differences in uptake of FOBt in England are partially explained
      by differences in cancer fatalism, self-rated health, and depression. IMPACT:
      This is one of only a few studies to examine mediators of the relationship
      between SES and screening uptake, and future research could test the
      effectiveness of interventions to reduce fatalistic beliefs to increase equality
      of uptake.

PMID- 21953116
TI  - Inflammation, focal atrophic lesions, and prostatic intraepithelial neoplasia
      with respect to risk of lethal prostate cancer.
AB  - BACKGROUND: A challenge in prostate cancer (PCa) management is identifying
      potentially lethal disease at diagnosis. Inflammation, focal prostatic atrophy,
      and prostatic intraepithelial neoplasia (PIN) are common in prostate tumor
      specimens, but it is not clear whether these lesions have prognostic
      significance. METHODS: We conducted a case-control study nested in a cohort of
      men diagnosed with stage T1a-b PCa through transurethral resection of the
      prostate in Sweden. Cases are men who died of PCa (n = 228). Controls are men who
      survived more than 10 years after PCa diagnosis without metastases (n = 387).
      Slides were assessed for Gleason grade, inflammation, PIN, and four subtypes of
      focal prostatic atrophy: simple atrophy (SA), postatrophic hyperplasia (PAH),
      simple atrophy with cyst formation, and partial atrophy. We estimated OR and 95%
      CI for odds of lethal PCa with multivariable logistic regression. RESULTS:
      Chronic inflammation and PIN were more frequently observed in tumors with PAH,
      but not SA. No specific type of atrophy or inflammation was significantly
      associated with lethal PCa overall, but there was a suggestion of a positive
      association for chronic inflammation. Independent of age, Gleason score, year of
      diagnosis, inflammation, and atrophy type, men with PIN were 89% more likely to
      die of PCa (95% CI: 1.04-3.42). CONCLUSION: Our data show that PIN, and perhaps
      presence of moderate or severe chronic inflammation, may have prognostic
      significance for PCa. IMPACT: Lesions in tumor adjacent tissue, and not just the
      tumor itself, may aid in identification of clinically relevant disease.

PMID- 21953117
TI  - Effect of static magnetic fields on the growth, photosynthesis and ultrastructure
      of Chlorella kessleri microalgae.
AB  - Microalgal biotechnology could generate substantial amounts of biofuels with
      minimal environmental impact if the economics can be improved by increasing the
      rate of biomass production. Chlorella kessleri was grown in a small-scale raceway
      pond and in flask cultures with the entire volume, 1% (v/v) at any instant,
      periodically exposed to static magnetic fields to demonstrate increased biomass
      production and investigate physiological changes, respectively. The growth rate
      in flasks was maximal at a field strength of 10 mT, increasing from 0.39 +/- 0.06
      per day for the control to 0.88 +/- 0.06 per day. In the raceway pond the 10 mT
      field increased the growth rate from 0.24 +/- 0.03 to 0.45 +/- 0.05 per day,
      final biomass from 0.88 +/- 0.11 to 1.56 +/- 0.18 g/L per day, and maximum
      biomass production from 0.11 +/- 0.02 to 0.38 +/- 0.04 g/L per day. Increased
      pigment, protein, Ca, and Zn content made the biomass produced with magnetic
      stimulation nutritionally superior. An increase in oxidative stress was measured
      indirectly as a decrease in antioxidant capacity from 26 +/- 2 to 17 +/- 1 umol
      antioxidant/g biomass. Net photosynthetic capacity (NPC) and respiratory rate
      were increased by factors of 2.1 and 3.1, respectively. Loss of NPC enhancement
      after the removal of magnetic field fit a first-order model well (R(2)  = 0.99)
      with a half-life of 3.3 days. Transmission electron microscopy showed enlarged
      chloroplasts and decreased thylakoid order with 10 mT treatment. By increasing
      daily biomass production about fourfold, 10 mT magnetic field exposure could make
      algal oil cost competitive with other biodiesel feedstocks.

PMID- 21953118
TI  - Laser-induced carotid artery injury model in the rat for therapeutic agent
      screening.
AB  - The aims of this study were to establish a rat model of carotid artery injury and
      to evaluate its suitability for evaluating therapeutic agents active against
      endothelial proliferation. Wistar-Kyoto rats were injected intravenously with the
      photochemically reactive dyes rose bengal or Evans blue, and the carotid artery
      was then focally irradiated with laser light of the appropriate wavelength.
      Histological sections of the carotid artery were analyzed to determine the
      appropriate parameters for this model. Ferulic acid was used to assess the
      suitability of this model for drug screening. No animal died as a result of the
      photochemical treatment. Endothelial proliferation in the carotid artery was
      observed in rats injected with rose Bengal and exposed to green laser light.
      Ferulic acid (400 mg/kg per day) significantly (p<0.05) reduced endothelial
      proliferation in the carotid artery 28 days after injury in dye-treated animals
      compared with vehicle-treated animals. This simple experimental rat model is
      suitable for studying factors inhibiting endothelial thickening after vessel
      damage and for developing therapeutic strategies active against endothelial
      proliferation.

PMID- 21953119
TI  - Interactions between bicarbonate, potassium, and magnesium, and sulfur-dependent
      induction of luminescence in Vibrio fischeri.
AB  - In spite of its central importance in research efforts, the relationship between
      seawater compounds and bacterial luminescence has not previously been
      investigated in detail. Thus, in this study, we investigated the effect of
      cations (Na(+) , K(+) , NH(4) (+) , Mg(2+) , and Ca(2+) ) and anions (Cl(-) ,
      HCO(3) (-) , CO(3) (2-) , and NO(3) (-) ) on the induction of both inorganic
      (sulfate, sulfite, and thiosulfate) and organic (L-cysteine and L-cystine) sulfur
      dependent luminescence in Vibrio fischeri. We found that HCO(3) (-) (bicarbonate)
      and CO(3) (2-) (carbonate), in the form of various compounds, had a stimulatory
      effect on sulfur-dependent luminescence. The luminescence induced by bicarbonate
      was further promoted by the addition of magnesium. Potassium also increased
      sulfur-dependent luminescence when sulfate or thiosulfate was supplied as the
      sole sulfur source, but not when sulfite, L-cysteine, or L-cystine was supplied.
      The positive effect of potassium was accelerated by the addition of magnesium
      and/or calcium. Furthermore, the additional supply of magnesium improved the
      induction of sulfite- or L-cysteine-dependent luminescence, but not the l-cystine
      dependent type. These results suggest that sulfur-dependent luminescence of V.
      fischeri under nutrient-starved conditions is mainly controlled by bicarbonate,
      carbonate, and potassium. In addition, our results indicate that an additional
      supply of magnesium is effective for increasing V. fischeri luminescence.

PMID- 21953120
TI  - Antioxidant supplement use after breast cancer diagnosis and mortality in the
      Life After Cancer Epidemiology (LACE) cohort.
AB  - BACKGROUND: There is concern that antioxidant supplement use during chemotherapy
      and radiation therapy may decrease treatment effects, yet the effects of such
      supplements on recurrence and survival are largely unknown. METHODS: The authors
      prospectively examined the associations between antioxidant use after breast
      cancer (BC) diagnosis and BC outcomes in 2264 women in the Life After Cancer
      Epidemiology (LACE) cohort. The cohort included women who were diagnosed with
      early stage, primary BC from 1997 to 2000 who enrolled, on average, 2 years
      postdiagnosis. Baseline data were collected on antioxidant supplement use since
      diagnosis and other factors. BC recurrence and mortality were ascertained, and
      hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using
      delayed entry Cox proportional hazards models. All tests of statistical
      significance were 2-sided. RESULTS: Antioxidant supplement use after diagnosis
      was reported by 81% of women. Among antioxidant users, frequent use of vitamin C
      and vitamin E was associated with a decreased risk of BC recurrence (vitamin C:
      HR, 0.73; 95% CI, 0.55-0.97; vitamin E: HR, 0.71; 95% CI, 0.54-0.94); and vitamin
      E use was associated with a decreased risk of all-cause mortality (HR, 0.76; 95%
      CI, 0.58-1.00). Conversely, frequent use of combination carotenoids was
      associated with increased risk of death from BC (HR, 2.07; 95% CI, 1.21-3.56) and
      all-cause mortality (HR, 1.75; 95% CI, 1.13-2.71). CONCLUSIONS: Frequent use of
      vitamin C and vitamin E in the period after BC diagnosis was associated with a
      decreased likelihood of recurrence, whereas frequent use of combination
      carotenoids was associated with increased mortality. The effects of antioxidant
      supplement use after diagnosis likely differ by type of antioxidant.

PMID- 21953121
TI  - Tumour necrosis factor-alpha drives Alport glomerulosclerosis in mice by
      promoting podocyte apoptosis.
AB  - Chronic renal failure involves the progressive loss of renal parenchymal cells.
      For example, Alport syndrome develops from mutated type IV collagen that fosters
      the digestion of glomerular basement membranes and podocyte loss, followed by
      progressive glomerulosclerosis, ie Alport nephropathy. Here we show that
      autosomal recessive Alport nephropathy in collagen 4a3-deficient mice is
      associated with increased intrarenal expression of the pro-apoptotic cytokine
      tumour necrosis factor-alpha (TNF-alpha) in glomerular cells including podocytes
      as well as in infiltrating leukocytes. We therefore hypothesized that TNF-alpha
      contributes to Alport glomerulosclerosis by inducing podocyte apoptosis. To
      address this issue, we treated 4-week-old collagen 4a3-deficient mice with either
      vehicle or the TNF-alpha antagonist etanercept for a period of 5 weeks.
      Etanercept treatment prolonged mean survival from 68 to 81 days as compared to
      vehicle-treated mice. The beneficial effect of etanercept on survival was
      associated with a significant improvement of the glomerulosclerosis score,
      proteinuria, and the glomerular filtration rate at 9 weeks of age. Etanercept
      treatment specifically reduced the numbers of apoptotic podocytes, increased
      total podocyte counts, and increased the renal mRNA expression of nephrin and
      podocin without affecting markers of renal inflammation. TNF-alpha-induced
      podocyte loss is a previously unrecognized pathological mechanism of Alport
      glomerulosclerosis, and TNF-alpha blockade might be a therapeutic option to delay
      the progression of Alport nephropathy and potentially of other forms of
      glomerulosclerosis.

PMID- 21953122
TI  - Potent antitumour activity of the combination of HSV-TK and endostatin armed
      oncolytic adeno-associated virus for bladder cancer in vitro and in vivo.
AB  - BACKGROUND: Gene therapy may offer a new tool for the treatment of bladder
      cancer. Previously, we have shown a significant antitumour effect in bladder
      cancer xenografts in a nude mouse model using intratumoural herpes simple virus
      thymidine (HSV-TK) and Endostatin gene therapy. OBJECTIVES: Given the high
      vascularity of human bladder cancer and the ability of HSV-TK or Endostatin
      monotherapy to eradicate the tumours, we decided to test a novel combination of
      cytotoxicity and antiangiogenisis gene therapy using intratumourally delivered
      HSV-TK and Endostatin adeno-associated viruses (AAVs). METHODS: We constructed
      plasmid AAV-TK-IRES-Endostatin (pAAV-TIE) and packaged the AAV particles contain
      gene fragments of HSV-TK and Endostatin. The function of HSV-TK and Endostatin
      was evaluated separately in vitro via T24 bladder tumour cells and human
      umbilical vein endothelial (HUVEC) cells. The combination anticancer effect of
      recombinant AAV-TIE (rAAV-TIE) was measured in vivo while rAAV-HSV-TK and rAAV
      Endostatin as control groups. RESULTS: In vitro, rAAV-TIE was found to induce a
      significant increase in apoptosis in HUVEC cells equally as rAAV-Endostatin and
      confirmed that the inhibition of endothelial cells mediated by rAAV-TIE was
      associated with the apoptotic process. rAAV-TIE was found to induce a significant
      increase in apoptosis in T24 cells equally as rAAV-HSV-TK and confirmed that the
      inhibition of T24 cells mediated by rAAV-TIE was associated with the apoptotic
      process too. In vivo, our results showed that the tumours in mice injected with
      the rAAV-TIE not only took significantly longer to emerge but also that their
      growth, once established, was significant slower than that of tumours grown,
      compared with single HSV-TK or Endostatin treated animals. CONCLUSIONS: We
      concluded that the inhibition of angiogenesis using Endostatin gene transfer,
      together with the cytotoxicity HSV-TK gene therapy, resulted in a significant
      antitumour effect compared to the single gene based therapy in BTCC. The results
      warrant further development of the combination gene therapy, and suggest that
      this approach, directed towards systemic efficiency, could be used as an
      additional treatment for human BTCC.

PMID- 21953123
TI  - Expanding the phenotype of late-onset Pompe disease: tongue weakness: a new
      clinical observation.
AB  - INTRODUCTION: Following the clinical observation of lingual weakness in 2
      patients with late-onset Pompe disease (LOPD), tongue strength was assessed in 19
      consecutive patients to determine the frequency and severity of this neurological
      sign. METHODS: Lingual strength was assessed using manual muscle testing; if
      weakness was present, severity was established as mild, moderate, or severe.
      RESULTS: All the patients exhibited lingual weakness, even 2 asymptomatic
      patients with a positive family history. Weakness was mild in 12 (63%), moderate
      in 6 (32%), and severe in 1 (5%). Dysarthria and/or dysphagia were observed or
      reported in 7 of 19 (37%) patients. CONCLUSIONS: Lingual weakness may be present
      as an axial sign of LOPD, even relatively early in the disease course, and may
      contribute to the differential diagnosis of this now treatable condition.
      Dysphagia and/or dysarthria may also occur. This finding further expands the
      phenotype of LOPD.

PMID- 21953125
TI  - General surgery in patients with a bleeding diathesis: how we do it.
AB  - BACKGROUND: This study was undertaken to assess perioperative management,
      postoperative complications, and the adequacy of perioperative plasma factor
      levels in a regional hemophilia center. METHODS: A total of 113 consecutive
      patients (75 men, 38 women; median age 48 years, range 18-86 years) with bleeding
      disorders undergoing general surgical and endoscopic procedures (144 procedures:
      15 urgent, 129 elective) were reviewed. The episodes were identified from a
      prospectively collected database at a regional hemophilia center from 1998 to the
      end of 2008. In all, 46% of the surgical patients had hemophilia A, 38% had von
      Willebrand disease, 6% had hemophilia B, 5% had factor XI deficiency, and 4% had
      other disorders. RESULTS: Procedures carried out were endoscopic in 40%, minor in
      25%, and intermediate and major in 35%. There were two postoperative deaths, both
      in patients undergoing urgent major procedures. Postoperative complications
      occurred after 7.6% (4.0% hemorrhagic, 3.6% nonhemorrhagic) of the procedures.
      Four of six patients with postoperative hemorrhage required further operative
      intervention. The median dose of clotting factor for Hemophilia A patients was
      2240 U for endoscopic procedures, 7500 U for minor procedures, and 23,500 U for
      intermediate/major procedures. In hemophiliacs, the mean preoperative plasma
      factor level attained was 129 IU/dl (SD 16) in patients who developed
      postoperative hemorrhagic complications and 125 IU/dl (SD 37) in those who did
      not have bleeding, indicating that in no case was hemorrhage attributable to
      inadequate factor replacement. CONCLUSIONS: General surgical and endoscopic
      procedures can be performed with low morbidity and mortality rates when there is
      appropriate factor replacement and good support from the hemophilia team.

PMID- 21953126
TI  - Sentinel lymph node biopsy for papillary thyroid cancer: commentary on the
      Efficacy of lateral neck sentinel lymph node biopsy in papillary thyroid
      carcinoma by Se Kyung Lee et al.

PMID- 21953124
TI  - Human U6 promoter drives stronger shRNA activity than its schistosome orthologue
      in Schistosoma mansoni and human fibrosarcoma cells.
AB  - Blood flukes or schistosomes are the causative agents of human schistosomiasis,
      one of the major neglected tropical diseases. Draft genome sequences have been
      reported for schistosomes, but functional genomics tools are needed to
      investigate the role and essentiality of the newly reported genes. Vector based
      RNA interference can contribute to functional genomics analysis for schistosomes.
      Using mRNA encoding reporter firefly luciferase as a model target, we compared
      the performance of a schistosome and a human promoter from the U6 gene in driving
      shRNA in human fibrosarcoma cells and in cultured schistosomes. Further, both a
      retroviral [Murine leukemia virus (MLV)] and plasmid (piggyBac, pXL-Bac II)
      vector were utilized. The schistosome U6 gene promoter was 270 bp in length, the
      human U6 gene promoter was 264 bp; they shared 41% identity. Following
      transduction of both HT1080 fibrosarcoma cells and schistosomules of Schistosoma
      mansoni with pseudotyped MLV virions, stronger knockdown of luciferase activity
      was seen with the virions encoding the human U6 promoter driven shRNA than the
      schistosome U6 promoter. A similar trend was seen after transfection of HT1080
      cells and schistosomules with the pXL-Bac-II constructs-stronger knockdown of
      luciferase activity was seen with constructs encoding the human compared to
      schistosome U6 promoter. The findings indicate that a human U6 gene promoter
      drives stronger shRNA activity than its schistosome orthologue, not only in a
      human cancer cell line but also in larval schistosomes. This RNA polymerase III
      promoter represents a potentially valuable component for vector based RNA
      interference studies in schistosomes and related platyhelminth parasites.

PMID- 21953129
TI  - Prognostic factors of papillary thyroid carcinoma vary according to sex and
      patient age.
AB  - BACKGROUND: We previously showed that preoperative and intraoperative evaluations
      of papillary thyroid carcinoma (PTC) are important for predicting a patient's
      prognosis, and we identified several prognostic factors. In this study, we
      investigated differences in the significance of these factors according to
      patient age and sex. METHODS: A total of 5768 PTC patients (608 men, 5160 women)
      without distant metastasis at diagnosis who underwent initial surgery between
      1987 and 2004 in Kuma Hospital were enrolled in this study. The postoperative
      follow-up period was 129 months (10.8 years) on average. RESULTS: We examined
      variations in the prognostic significance of tumor size >4 cm (T), extrathyroid
      extension (Ex), node metastasis >3 cm (N), and extranodal (tumor extension (LN
      Ex)--which were identified as prognostic factors in our previous studies--in four
      subsets of patients based on age and sex. In older women, Ex was the most
      significant prognostic factor for local and distant recurrences and carcinoma
      death. In older men as well, Ex was a strong prognostic factor, but N had a
      prognostic impact similar to Ex for local recurrence and LN-Ex was the strongest
      prognostic factor for carcinoma death. N was the most significant prognostic
      factor for local and distant recurrences and carcinoma death in younger women. T
      and N independently affected local recurrence with similar significance, and Ex
      was the only independent prognostic factor for distant recurrence in younger men.
      Because only two of the younger men in this series died of carcinoma, we could
      not analyze prognostic factors for carcinoma death in this subgroup. CONCLUSIONS:
      The significance of prognostic factors of PTC varied according to patient sex and
      age, which might contribute not only to evaluating the prognosis but also to
      deciding therapeutic strategies for each patient. Because Ex was a prominent
      prognostic factor for local and distant recurrences in older patients, careful
      and extensive excision of the site of carcinoma extension and extensive lymph
      node dissection should be performed, especially for older patients with Ex.

PMID- 21953130
TI  - Indications for staging laparoscopy in clinical T4M0 gastric cancer.
AB  - BACKGROUND: This study was undertaken to determine the efficacy of the clinical
      indications for performing staging laparoscopy for locally advanced gastric
      cancer to detect peritoneal metastasis or positive cytology findings. METHODS:
      The study included 231 patients with T4 gastric cancer without hematogenous or
      clinically evident peritoneal metastasis. The clinicopathologic features,
      including T and N factors, were diagnosed by clinical staging. The relation
      between the clinicopathologic features and the presence of peritoneal metastasis
      or lavage cytology at surgery was analyzed. RESULTS: A total of 31 patients
      underwent staging laparoscopy; 200 others underwent open surgery as a primary
      treatment. Both peritoneal metastasis and lavage cytology were negative in 145
      (62.8%) patients, whereas peritoneal metastasis or lavage cytology was positive
      in 86 patients (37.2%). When calculating diagnostic accuracy in the 23 patients
      who underwent open laparotomy after staging laparoscopy, the accuracy rate was
      95.7%. A multivariate analysis showed that a tumor location involving three
      portions; macroscopic type 3, 4, or 5; and positive lymph node metastasis to all
      three is significantly correlated with either peritoneal metastasis or positive
      cytology. When patients had two or three factors among these three independent
      risk factors, peritoneal metastasis or positive cytology could be detected with
      91.9% sensitivity and 46.7% positive predictive value. CONCLUSIONS: The selection
      of T4 tumors based on clinically evaluable risk factors is therefore considered
      useful for detecting peritoneal metastasis efficiently and hence avoiding
      unnecessary staging laparoscopy.

PMID- 21953131
TI  - The utility of a noninvasive 13C-acetate breath test to predict quality of life
      after gastrectomy.
AB  - BACKGROUND: The radioscintigraphic technique has been accepted as the standard by
      which to measure gastric emptying but it is invasive and expensive. A 13C-acetate
      breath test was reported to be a noninvasive and reliable method. The aim of this
      study was to investigate the accuracy of a 13C-acetate breath test in reflecting
      gastric function and the relationship between food intake and change in body
      weight after distal gastrectomy. METHODS: Twenty-five patients who had undergone
      curative distal gastrectomy with Billroth-I reconstruction for gastric cancer and
      ten healthy volunteers were included in the study. The gastrectomy group was
      divided into two groups: the stasis group and the nonstasis group. The breath
      test was performed on the patients with gastrectomy and the healthy volunteers,
      and the time lag between ingestion and the peak of (13)CO(2) expiration (T lag)
      was calculated. The manometry study was performed on the patients who underwent
      gastrectomy and the motility index (MI) was calculated. The relationships between
      T lag and food intake and body weight were examined. RESULTS: The T lag was
      significantly shorter in the nonstasis group than in the stasis group. The MI in
      the duodenum in the nonstasis group was significantly larger than that in the
      stasis group. There was significant correlation between T lag and food intake,
      but no significant correlation between T lag and body weight. CONCLUSION: The 13C
      acetate breath test might be useful not only for the evaluation of the function
      of the remnant stomach, but also for the prediction of postoperative status.

PMID- 21953133
TI  - Cigarette sales in pharmacies in the USA (2005-2009).
AB  - BACKGROUND: Several US jurisdictions have adopted policies prohibiting pharmacies
      from selling tobacco products. Little is known about how pharmacies contribute to
      total cigarette sales. METHODS: Pharmacy and total cigarette sales in the USA
      were tabulated from AC Nielsen and Euromonitor, respectively, for the years 2005
      2009. Linear regression was used to characterise trends over time, with observed
      trends extrapolated to 2020. RESULTS: Between 2005 and 2009, pharmacy cigarette
      sales increased 22.72% (p=0.004), while total cigarette sales decreased 17.43%
      (p=0.015). In 2005, pharmacy cigarette sales represented 3.05% of total cigarette
      sales, increasing to 4.54% by 2009. Extrapolation of these findings resulted in
      estimated pharmacy cigarette sales of 14.59% of total US cigarette sales by 2020.
      CONCLUSIONS: Cigarette sales in American pharmacies have risen in recent years,
      while cigarette sales nationally have declined. If current trends continue,
      pharmacy cigarette market share will, by 2020, increase to more than four times
      the 2005 share.

PMID- 21953132
TI  - Decreased collagen-induced arthritis severity and adaptive immunity in MKK-6
      deficient mice.
AB  - OBJECTIVE: The MAPK kinases MKK-3 and MKK-6 regulate p38 MAPK activation in
      inflammatory diseases such as rheumatoid arthritis (RA). Previous studies
      demonstrated that MKK-3 or MKK-6 deficiency inhibits K/BxN serum-induced
      arthritis. However, the role of these kinases in adaptive immunity-dependent
      models of chronic arthritis is not known. The goal of this study was to evaluate
      MKK-3 and MKK-6 deficiency in the collagen-induced arthritis (CIA) model.
      METHODS: Wild-type (WT), MKK-3(-/-) , and MKK-6(-/-)  mice were immunized with
      bovine type II collagen. Disease activity was evaluated by semiquantitative
      scoring, histologic assessment, and micro-computed tomography. Serum anticollagen
      antibody levels were quantified by enzyme-linked immunosorbent assay. In vitro T
      cell cytokine response was measured by flow cytometry and multiplex analysis.
      Expression of joint cytokines and matrix metalloproteinases (MMPs) was determined
      by quantitative polymerase chain reaction. RESULTS: MKK-6 deficiency markedly
      reduced arthritis severity compared with that in WT mice, while the absence of
      MKK-3 had an intermediate effect. Joint damage was minimal in arthritic MKK-6(-/
      )  mice and intermediate in MKK-3(-/-)  mice compared with WT mice. MKK-6(-/-) 
      mice had modestly lower levels of pathogenic anticollagen antibodies than did WT
      or MKK-3(-/-)  mice. In vitro T cell assays showed reduced proliferation and
      interleukin-17 (IL-17) production by lymph node cells from MKK-6(-/-)  mice in
      response to type II collagen. Gene expression of synovial IL-6, MMP-3, and MMP-13
      was significantly inhibited in MKK-6-deficient mice. CONCLUSION: Reduced disease
      severity in MKK-6(-/-)  mice correlated with decreased anticollagen antibody
      responses, indicating that MKK-6 is a crucial regulator of inflammatory joint
      destruction in CIA. MKK-6 is a potential therapeutic target in complex diseases
      involving adaptive immune responses, such as RA.

PMID- 21953134
TI  - [Neuropsychology of psychoeducation in schizophrenia: results of the Munich
      COGPIP study].
AB  - BACKGROUND: The aim of the study was to examine whether the efficacy of
      psychoeducation in patients with schizophrenia is dependent on their cognitive
      performance and if a preceding cognitive training can enhance the therapeutic
      effects of psychoeducation. PATIENTS AND METHODS: A total of 116 inpatients were
      randomly assigned to either a standardized cognitive training (COGPACK) or to
      routine occupational therapy, followed by a psychoeducational group program of 8
      sessions within 4 weeks for all study patients. The effects of cognitive training
      and psychoeducation were assessed directly afterwards and in a follow-up after 9
      months. RESULTS: The patient knowledge and compliance improved. Neurocognition
      and especially memory acquisition significantly predicted illness knowledge after
      psychoeducation, whereas psychopathology did not. No differential effects of the
      COGPACK training were found. After 9 months 75% of the patients showed a very
      good compliance and the readmission rate was 18%. The results were comparable
      under both study conditions. CONCLUSION: Besides baseline illness knowledge
      neurocognition was the only significant predictor for illness knowledge after
      psychoeducation. Patients with cognitive deficits can profit from psychoeducation
      in the long run as well. In future it should be examined whether a modified
      cognitive training program could achieve a faster improvement of the illness
      knowledge.

PMID- 21953135
TI  - Intra- and inter-rater reliability for analysis of hyoid displacement measured
      with sonography.
AB  - PURPOSE: Anterior hyoid displacement is essential for efficient swallowing and is
      usually investigated with videofluoroscopy. Ultrasound offers a less expensive
      and noninvasive method of investigation. The present study investigated the
      viability of a novel method of quantifying hyoid displacement from sonograms
      using an anatomic reference point, through an evaluation of inter- and intra
      rater reliability. METHODS: Three raters reviewed the sonographic video sweeps of
      five discrete swallows from each of five participants for inter-rater
      reliability. The primary investigator measured each swallow on two occasions for
      intra-rater reliability. Electronic calipers were used to measure distances from
      a "rest" frame prior to the swallow of interest and a "maximal displacement"
      frame, at which the hyoid bone was at maximal anterior displacement during each
      swallow. RESULTS: Single-measure intraclass correlation coefficient was high for
      inter-rater agreement at 0.86 for rest measures and 0.86 for maximal
      displacement. Intra-rater reliability was even higher at 0.95 for rest and 0.98
      for maximal displacement. CONCLUSIONS: These preliminary results suggest that by
      using a novel analysis approach involving an anatomic reference point, raters can
      achieve high agreement on measurement of position of hyoid at maximal
      displacement relative to rest.

PMID- 21953137
TI  - Adenovirus-36 seropositivity enhances effects of nutritional intervention on
      obesity, bright liver, and insulin resistance.
AB  - BACKGROUND: Obesity and liver steatosis are both currently attributed to
      inappropriate lifestyle and nutrition. Higher prevalence of human adenovirus Ad36
      seropositivity (Ad36+) is reported only in obesity. AIMS: To investigate whether
      a lifestyle-nutritional intervention achieves different outcomes in NAFLD
      patients, i.e., if is blunted or enhanced according to Ad36 seropositivity
      status. METHODS: One-year nutritional intervention was planned and accomplished
      for 62 non-alcoholic fatty liver disease overweight-obese patients, studied by
      liver ultrasound, evaluating Bright Liver Score (BLS), by Homeostatic Model
      assessment of Insulin Resistance (HOMA), by body composition and Ad36+ assay.
      Lower salt/lower calories Mediterranean diet, physical activity increase, smoking
      withdrawal and lifestyle counseling, provided by a health psychologist, were
      given. RESULTS: Ad36 seropositive patients have baseline greater BMI with the
      same level of BLS. Different prevalence of post-interventional response,
      significantly greater among Ad36+ patients, is observed: greater decrease of
      obesity, assessed by BMI, greater reduction of insulin resistance, assessed by
      HOMA and higher prevalence of bright liver disappearance. A BMI-adjusted multiple
      linear regression model explains significantly 23.8% (p < 0.04) of the variance;
      significant predictive variables are Ad36 seropositivity (p < 0.012) and fat mass
      loss (p < 0.011) accounting for the variance of the occurrence of bright liver
      disappearance. CONCLUSIONS: Ad36 previous infection is significantly associated
      with enhanced weight loss, bright liver disappearance, and recovery of insulin
      sensitivity through the chosen tailored nutritional interventional treatment.
      Nonetheless, Ad36 seronegative NAFLD patients' fatty liver pattern improves, at a
      lower extent, also without significant weight loss: an effect of dietary changes
      profile, Mediterranean diet, not only of lowered food caloric intake, is
      conceivably operating.

PMID- 21953138
TI  - Predictors of liver transplant eligibility for patients with hepatocellular
      carcinoma in a safety net hospital.
AB  - BACKGROUND: Liver transplantation for patients with hepatocellular carcinoma
      (HCC) affords excellent long-term survival but is limited to patients with early
      stage tumors. Predictors for orthotopic liver transplantation eligibility are not
      well defined for patients in a safety-net hospital system. AIMS: To clarify the
      clinical presentation of HCC and define predictors for early stage disease in a
      racially diverse safety-net hospital system. METHODS: We retrospectively reviewed
      records of patients with HCC presenting to a large urban county hospital between
      January 1998 and October 2007. Logistic regression analysis was used to find
      predictors of OLT eligibility. RESULTS: Of the 266 patients with HCC, 62% had
      multiple tumors, 47% had portal vein thrombosis and only 22% were potential liver
      transplant candidates based on Milan criteria. Male gender (OR 0.33; 95% CI 0.17
      0.65) and AFP levels > 20 ng/mL (OR 0.22; 95% CI 0.11-0.45) were negative
      predictors of liver transplant eligibility. Age, race, and underlying viral liver
      disease were not significant predictors of early tumor stage. CONCLUSIONS: A
      minority of HCC patients in a safety-net hospital are eligible for liver
      transplant at the time of diagnosis. Men have more advanced tumors at
      presentation, which may be related to more aggressive tumor biology or
      differential rates of HCC surveillance.

PMID- 21953139
TI  - Incidence and risk factors of hepatocellular carcinoma recurrence after liver
      transplantation in the MELD era.
AB  - BACKGROUND AND AIMS: Deceased donor liver transplantation (DDLT) rates for
      candidates with hepatocellular carcinoma (HCC) have significantly increased in
      the MELD era because of the extra priority given to these candidates. We examined
      the incidence and pre-DDLT radiological and donor factors associated with post
      DDLT HCC recurrence in the MELD era. METHODS: Outcomes of HCC candidates aged
      >=18 years that underwent DDLT between 2/28/02 and 6/30/08 (n = 94) were
      reviewed. The primary outcome was biopsy-proven post-LT HCC recurrence at any
      site. Kaplan-Meier analysis was used to calculate the cumulative incidence and
      Cox regression was used to identify the predictors of post-LT HCC recurrence.
      RESULTS: The median age of the 94 candidates who met the study criteria was 54
      years, 64% had hepatitis C, median lab MELD was 13, and median pre-LT AFP was 47
      ng/dl. Based upon pre-DDLT imaging, 94% candidates met the Milan criteria. The
      median waiting time to transplant was 47 days and 27% received pre-DDLT loco
      regional therapy. Seventeen (18%) developed HCC recurrence after 2.1 median years
      with a cumulative incidence of 6.8, 12, and 19% at 1, 2, and 3 years post-DDLT.
      The pre-DDLT number of lesions (p = 0.015), largest lesion diameter (p = 0.008),
      and higher donor age (p = 0.002) were the significant predictors of HCC
      recurrence after adjusting for pre-LT loco-regional therapy and waiting time.
      Post-LT HCC recurrence (p < 0.0001) and higher donor age (p = 0.029) were
      associated with lower post-LT survival. CONCLUSIONS: Post-LT HCC recurrence is
      higher in our MELD era cohort than the reported rate of 8% at 4 years in
      Mazzaferro et al.'s study. The risk of HCC recurrence was significantly
      associated with the number of lesions and size of the largest lesion at the time
      of DDLT as well as with older donor age. Risk stratification using a predictive
      model for post-LT HCC recurrence based on pre-LT imaging and donor factors may
      help guide candidate selection and tailoring of HCC surveillance strategies after
      LT.

PMID- 21953136
TI  - Transforming growth factor beta signaling in adult cardiovascular diseases and
      repair.
AB  - The majority of children with congenital heart disease now live into adulthood
      due to the remarkable surgical and medical advances that have taken place over
      the past half century. Because of this, adults now represent the largest age
      group with adult cardiovascular diseases. It includes patients with heart
      diseases that were not detected or not treated during childhood, those whose
      defects were surgically corrected but now need revision due to maladaptive
      responses to the procedure, those with exercise problems and those with age
      related degenerative diseases. Because adult cardiovascular diseases in this
      population are relatively new, they are not well understood. It is therefore
      necessary to understand the molecular and physiological pathways involved if we
      are to improve treatments. Since there is a developmental basis to adult
      cardiovascular disease, transforming growth factor beta (TGFbeta) signaling
      pathways that are essential for proper cardiovascular development may also play
      critical roles in the homeostatic, repair and stress response processes involved
      in adult cardiovascular diseases. Consequently, we have chosen to summarize the
      current information on a subset of TGFbeta ligand and receptor genes and related
      effector genes that, when dysregulated, are known to lead to cardiovascular
      diseases and adult cardiovascular deficiencies and/or pathologies. A better
      understanding of the TGFbeta signaling network in cardiovascular disease and
      repair will impact genetic and physiologic investigations of cardiovascular
      diseases in elderly patients and lead to an improvement in clinical
      interventions.

PMID- 21953140
TI  - Xenon-inhalation computed tomography for noninvasive quantitative measurement of
      tissue blood flow in pancreatic tumor.
AB  - BACKGROUND AND AIMS: The purpose of this prospective study was to demonstrate the
      ability to measure pancreatic tumor tissue blood flow (TBF) with a noninvasive
      method using xenon inhalation computed tomography (xenon-CT) and to correlate TBF
      with histological features, particularly microvascular density (MVD). METHODS:
      TBFs of pancreatic tumors in 14 consecutive patients were measured by means of
      xenon-CT at diagnosis and following therapy. Serial abdominal CT scans were
      obtained before and after inhalation of nonradioactive xenon gas. TBF was
      calculated using the Fick principle. Furthermore, intratumoral microvessels were
      stained with anti-CD34 monoclonal antibodies before being quantified by light
      microscopy (*200). We evaluated MVD based on CD34 expression and correlated it
      with TBF. RESULTS: The quantitative TBF of pancreatic tumors measured by xenon CT
      ranged from 22.3 to 111.4 ml/min/100 g (mean +/- SD, 59.6 +/- 43.9 ml/min/100 g).
      High correlation (r = 0.885, P < 0.001) was observed between TBF and intratumoral
      MVD. CONCLUSION: Xenon-CT is feasible in patients with pancreatic tumors and is
      able to accurately estimate MVD noninvasively.

PMID- 21953141
TI  - Eradication of H. pylori did not improve abnormal sonic hedgehog expression in
      the high risk group for gastric cancer.
AB  - BACKGROUND: Sonic hedgehog (SHH) acts as a proliferation factor in both the
      normal mucosa and in malignant lesions. Helicobacter pylori-associated atrophic
      gastritis is characterized by loss of SHH. AIM: The purpose of this study was to
      investigate the effects of H. pylori eradication on SHH mRNA and methylation
      levels in the patients at high risk for gastric cancer comparing to those in the
      controls. METHODS: Gastric corpus biopsies taken from 20 patients with endoscopic
      resection for early gastric cancer and 14 sex- and age-matched controls before
      and 1 year after eradication were examined for SHH and downstream regulators mRNA
      expression using whole biopsy specimens and microdissected gastric glands.
      Methylation of SHH promoter was evaluated using quantitative methylation-specific
      PCR. RESULTS: SHH mRNA levels eradication were significantly lower (2.75 * 10(-2)
      vs. 7.37 * 10(-2), P = 0.004) in the cancer group than in the controls. PTCH and
      BMP4 mRNA levels as well as MUC5AC were significantly increased only in the
      control group and were significantly higher in the controls than those in the
      cancer group after eradication. After eradication, SHH methylation levels in the
      non-metaplastic glands were significantly higher (86.4% vs. 22.2%, P < 0.001) in
      the cancer group than in the controls. CONCLUSIONS: H. pylori eradication can
      enhance SHH and its downstream regulators expression diminishing SHH methylation
      and reverse gastric phenotype, but not in the patients with high risk for gastric
      cancer.

PMID- 21953142
TI  - Gastric tube reconstruction reduces postoperative gastroesophageal reflux in
      adenocarcinoma of esophagogastric junction.
AB  - BACKGROUND: The anastomosis of gastric remnant to esophagus after proximal
      gastrectomy is the traditional surgical treatment procedure for patients with
      types II and III adenocarcinoma of esophagogastric junction. However, the
      postoperative complications such as gastroesophageal reflux are frequent. AIMS:
      To assess the outcome of the intraperitoneal anastomosis of the reconstructed
      gastric tube to esophagus after proximal gastrectomy for types II and III
      adenocarcinoma of esophagogastric junction. METHODS: Seventy-six consecutive
      patients with preoperative diagnosis of type II or type III adenocarcinoma of
      esophagogastric junction were recruited. Forty-one patients had the traditional
      anastomosis of gastric remnant to esophagus and 35 patients underwent an
      anastomosis of esophagus to a gastric tube that was constructed from the gastric
      remnant after proximal gastrectomy. RESULTS: Twenty-three (56.1%) versus 12
      (28.6%) patients (p = 0.016) complained various discomforts and/or were diagnosed
      with complications in the traditional group and gastric tube group, respectively,
      although there were no significant differences between the two groups in
      demographic data and pathological characteristics. Fourteen (34.1%) versus five
      (14.3%) patients (p = 0.046) complained of heartburn or acid regurgitation and
      nine (22.0%) versus two (5.7%) patients (p = 0.045) were confirmed reflux
      esophagitis in the traditional group and the gastric tube group, respectively.
      CONCLUSIONS: The intraperitoneal anastomosis of the reconstructed gastric tube to
      esophagus demonstrates less complaints of gastroesophageal reflux and reflux
      esophagitis than the traditional anastomosis of gastric remnant to esophagus in
      the surgical treatment of types II and III adenocarcinoma of esophagogastric
      junction in 1-year follow-up.

PMID- 21953143
TI  - Circulating markers of vascular injury and angiogenesis in antineutrophil
      cytoplasmic antibody-associated vasculitis.
AB  - OBJECTIVE: To identify biomarkers that distinguish between active antineutrophil
      cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and remission in a manner
      superior or complementary to established markers of systemic inflammation.
      METHODS: Markers of vascular injury and angiogenesis were measured before and
      after treatment in a large clinical trial in AAV: 163 subjects enrolled in the
      Rituximab in ANCA-Associated Vasculitis trial were screened for the present
      study. Serum levels of E-selectin, intercellular adhesion molecule 3 matrix
      metalloproteinase protein 1 (MMP-1), MMP-3, MMP-9, P-selectin, thrombomodulin,
      and vascular endothelial growth factor were measured at study screening (time of
      active disease) and at month 6. Erythrocyte sedimentation rate (ESR) and C
      reactive protein (CRP) levels had been measured at the time of the clinical
      visit. The primary outcome measure was the difference in marker level between
      screening and month 6 among patients whose disease was in remission (Birmingham
      Vasculitis Activity Score for Wegener's granulomatosis [BVAS/WG] score of 0) at
      month 6. RESULTS: All patients had severe active vasculitis at screening (mean +/
      SD BVAS/WG score 8.6 +/- 3.2). Among the 123 patients whose disease was
      clinically in remission at month 6, levels of all markers except E-selectin
      showed significant declines. MMP-3 levels were also higher among the 23 patients
      with active disease at month 6 than among the 123 patients whose disease was in
      remission. MMP-3 levels correlated weakly with ESR and CRP levels. CONCLUSION:
      Many markers of vascular injury and angiogenesis are elevated in severe active
      AAV and decline with treatment, but MMP-3 appears to distinguish active AAV from
      remission better than the other markers studied. Further study of MMP-3 is
      warranted to determine its clinical utility in combination with conventional
      markers of inflammation and ANCA titers.

PMID- 21953144
TI  - Myeloid suppressor cells induced by hepatitis C virus suppress T-cell responses
      through the production of reactive oxygen species.
AB  - Impaired T-cell responses in chronic hepatitis C virus (HCV) patients have been
      reported to be associated with the establishment of HCV persistent infection.
      However, the mechanism for HCV-mediated T-cell dysfunction is yet to be defined.
      Myeloid-derived suppressor cells (MDSCs) play a pivotal role in suppressing T
      cell responses. In this study we examined the accumulation of MDSCs in human
      peripheral blood mononuclear cells (PBMCs) following HCV infection. We found that
      CD33(+) mononuclear cells cocultured with HCV-infected hepatocytes, or with HCV
      core protein, suppress autologous T-cell responses. HCV core-treated CD33(+)
      cells exhibit a CD14(+) CD11b(+/low) HLADR(-/low) phenotype with up-regulated
      expression of p47(phox) , a component of the NOX2 complex critical for reactive
      oxygen species (ROS) production. In contrast, immunosuppressive factors, arginase
      1 and inducible nitric oxide synthase (iNOS), were not up-regulated. Importantly,
      treatment with an inactivator of ROS reversed the T-cell suppressive function of
      HCV-induced MDSCs. Lastly, PBMCs of chronic HCV patients mirror CD33(+) cells
      following treatment with HCV core where CD33(+) cells are CD14(+) CD11b(+) HLADR(
      /low) , and up-regulate the expression of p47(phox). CONCLUSION: These results
      suggest that HCV promotes the accumulation of CD33(+) MDSC, resulting in ROS
      mediated suppression of T-cell responsiveness. Thus, the accumulation of MDSCs
      during HCV infection may facilitate and maintain HCV persistent infection.

PMID- 21953177
TI  - Kinetic and thermodynamic investigation of mancozeb degradation in tomato
      homogenate during thermal processing.
AB  - BACKGROUND: The kinetic and thermodynamic parameters of mancozeb degradation in
      tomato homogenates under the conditions prevailing in the manufacture of tomato
      products (at 60-100  degrees C for 0-60 min) were investigated. A gas
      chromatography-mass spectrometry method was used to analyse residual mancozeb in
      tomato homogenate. Ethylenethiourea (ETU), the main toxic degradation product of
      mancozeb, was measured by high-performance liquid chromatography (HPLC)-with
      photodiode array detector (PDA). RESULTS: The degradation of mancozeb and the
      formation of ETU in tomato homogenates were adequately described as first-order
      kinetics. Dependence of the rate constant followed the Arrhenius relationship.
      Apparent activation energies, temperature coefficients, half time and time to
      reduce to 90% of the initial value of mancozeb were calculated as kinetic
      parameters. The thermodynamic parameters of mancozeb were also described as
      Deltag(d) = - 2.440 and 7.074 kJ mol-1; Deltah(d) = - 32.555 and - 42.767 kJ mol
      1; Deltas(d) = - 0.090 and - 0.150 kJ mol-1 K-1; K(e) = 0.414 and 9.797 L g-1 for
      333 and 373 K respectively. CONCLUSION: Current findings may shed light on the
      reduction of mancozeb residue and its toxic degradation product during thermal
      processing of tomatoes and may also be valuable in awareness and prevention of
      potential risks from dietary exposure.

PMID- 21953178
TI  - Anti-tumor activity of a B-cell receptor-targeted peptide in a novel disseminated
      lymphoma xenograft model.
AB  - Receptor-targeted therapies have become standard in the treatment of various
      lymphomas. In view of its unparalleled specificity for the malignant B-cell
      clone, the B-cell receptor (BCR) on B cell lymphoma cells is a potential
      therapeutic target. We have used two BCR epitope mimicking peptides binding to
      the Burkitt's lymphoma cell lines CA46 and SUP-B8. We proved their functionality
      by demonstrating calcium flux and BCR-mediated endocytosis upon peptide receptor
      binding. Toxicity experiments in vitro via cross-linking of the BCR with
      tetramerized epitope mimics lead to apoptosis in both cell lines but was far more
      effective in SUP-B8 cells. We established a SUP-B8-based disseminated Burkitt's
      lymphoma model in NOD/SCID mice. Treatment of tumor-bearing mice with
      tetramerized epitope mimics had significant anti-tumor effects in vivo. We
      conclude that peptide-mediated, BCR-targeted therapy is a promising approach
      which may be explored and further developed for application in highly aggressive
      lymphoma.

PMID- 21953179
TI  - Comparative genomics and functional analysis of the NiaP family uncover
      nicotinate transporters from bacteria, plants, and mammals.
AB  - The transporter(s) that mediate uptake of nicotinate and its N-methyl derivative
      trigonelline are not known in plants, and certain mammalian nicotinate
      transporters also remain unidentified. Potential candidates for these missing
      transporters include proteins from the ubiquitous NiaP family. In bacteria, niaP
      genes often belong to NAD-related regulons, and genetic evidence supports a role
      for Bacillus subtilis and Acinetobacter baumannii NiaP proteins in uptake of
      nicotinate or nicotinamide. Other bacterial niaP genes are, however, not in NAD
      related regulons but cluster on the chromosome with choline-related (e.g.,
      Ralstonia solanacearum and Burkholderia xenovorans) or thiamin-related (e.g.,
      Thermus thermophilus) genes, implying that they might encode transporters for
      these compounds. Radiometric uptake assays using Lactococcus lactis cells
      expressing NiaP proteins showed that B. subtilis, R. solanacearum, and B.
      xenovorans NiaP transport nicotinate via an energy-dependent mechanism. Likewise,
      NiaP proteins from maize (GRMZM2G381453, GRMZM2G066801, and GRMZM2G081774),
      Arabidopsis (At3g13050), and mouse (SVOP) transported nicotinate; the Arabidopsis
      protein also transported trigonelline. In contrast, T. thermophilus NiaP
      transported only thiamin. None of the proteins tested transported choline or the
      thiazole and pyrimidine products of thiamin breakdown. The maize and Arabidopsis
      NiaP proteins are the first nicotinate transporters reported in plants, the
      Arabidopsis protein is the first trigonelline transporter, and mouse SVOP appears
      to represent a novel type of mammalian nicotinate transporter. More generally,
      these results indicate that specificity for nicotinate is conserved widely, but
      not absolutely, among pro- and eukaryotic NiaP family proteins.

PMID- 21953180
TI  - Mouse intermittent hypoxia mimicking apnoea of prematurity: effects on
      myelinogenesis and axonal maturation.
AB  - Premature babies are at high risk for both infantile apnoea and long-term
      neurobehavioural deficits. Recent studies suggest that diffuse structural changes
      in brain white matter are a positive predictor of poor cognitive outcomes. Since
      oligodendrocyte maturation, myelination, axon development, and synapse formation
      mainly occur in the third trimester of gestation and first postnatal year,
      infantile apnoea could lead to and/or exaggerate white matter impairments in
      preterm neonates. Therefore, we investigated oligodendroglia and axon development
      in a neonatal mouse model of intermittent hypoxia between postnatal days 2 and
      10. During critical phases of central nervous system development, intermittent
      hypoxia induced hypomyelination in the corpus callosum, striatum, fornix, and
      cerebellum, but not in the pons or spinal cord. Intermittent hypoxia-elicited
      alterations in myelin-forming processes were reflected by decreased expression of
      myelin proteins, including MBP, PLP, MAG, and CNPase, possibly due to arrested
      maturation of oligodendrocytes. Ultrastructural abnormalities were apparent in
      the myelin sheath and axon. Immature oligodendrocytes were more vulnerable to
      neonatal intermittent hypoxia exposures than developing axons, suggesting that
      hypomyelination may contribute, at least partially, to axonal deficits.
      Insufficient neurofilament synthesis with anomalous components of neurofilament
      subunits, beta-tubulin, and MAP2 isoforms indicated immaturity of axons in
      intermittent hypoxia-exposed mouse brains. In addition, down-regulation of
      synapsin I, synaptophysin, and Gap-43 phosphorylation suggested a potential stunt
      in axonogenesis and synaptogenesis. The region-selective and complex impairment
      in brain white matter induced by intermittent hypoxia was further associated with
      electrophysiological changes that may underlie long-term neurobehavioural
      sequelae.

PMID- 21953182
TI  - Focus in honor of David Muddiman, recipient of the 2010 Biemann Medal.

PMID- 21953181
TI  - Interactions between Zn and bacteria in marine tropical coastal sediments.
AB  - PURPOSE: The main goals of this study were (1) to examine the effects of zinc on
      the microbial community structure of anthropogenically impacted sediments in a
      tropical coastal ecosystem and (2) to determine whether these microbial benthic
      communities may enhance the adsorption of zinc. METHODS: The interactions between
      zinc and bacteria in tropical sediments were studied in sediment microcosms
      amended with 2.5 mg L-1 of Zn in the water phase and incubated for 8 days under
      different environmental conditions, oxic/anoxic and glucose addition. At the end
      of incubation, microbial structure was assessed by molecular fingerprints (T
      RFLP) analysis and Zn speciation in the sediment was determined by sequential
      extraction. RESULTS: In the three studied sediments, Zn spiking resulted in only
      slight changes in bacterial community structure. In contrast, the addition of low
      concentrations of glucose (5 mM) strongly modified the bacterial community
      structure: <20% of similarity with the initial structure concomitant with a
      strong diminution of the specific richness. Overall, these results suggest that
      highly labile organic matter has a larger impact on microbial structure than
      heavy metal. These weak impacts of Zn on bacteria diversity might be partly
      explained by (1) the strong adsorption of Zn in the presence of bacteria and/or
      (2) the incorporation of Zn into a nonbioavailable fraction. Nevertheless, Zn
      spiking resulted in significant changes in nutrient cycles, suggesting that
      bacterial metabolisms were impacted by the heavy metal. This led to an increase
      in nutrient supplies to the water column, potentially enhancing eutrophication in
      a nutrient-limited, oligotrophic ecosystem.

PMID- 21953183
TI  - John Bennett Fenn: a curious road to the prize.
AB  - John Bennett Fenn shared the 2002 Nobel Prize in Chemistry for his development of
      electrospray ionization (ESI). There are several excellent, in-depth biographical
      reviews of Fenn's scientific career Fenn (Angew. Chem., Int. Ed. 42, 3871-3894,
      2003) and Fenn (Annu. Rev. Phys. Chem. 47, 1-41, 1996). The focus of this report
      is to trace the random walk nature of Fenn's career path and to highlight those
      critical events along that path that led him to the important work for which he
      was recognized, the development of ESI as a means of ionizing large molecules and
      interfacing the liquid chromatograph to the mass spectrometer. In addition, this
      report should hopefully convey something of the curious, generous, kind, and
      outgoing nature of the man.

PMID- 21953184
TI  - Hydrophobic derivatization of N-linked glycans for increased ion abundance in
      electrospray ionization mass spectrometry.
AB  - A library of neutral, hydrophobic reagents was synthesized for use as
      derivatizing agents in order to increase the ion abundance of N-linked glycans in
      electrospray ionization mass spectrometry (ESI MS). The glycans are derivatized
      via hydrazone formation and are shown to increase the ion abundance of a glycan
      standard more than 4-fold. Additionally, the data show that the systematic
      addition of hydrophobic surface area to the reagent increases the glycan ion
      abundance, a property that can be further exploited in the analysis of glycans.
      The results of this study will direct the future synthesis of hydrophobic
      reagents for glycan analysis using the correlation between hydrophobicity and
      theoretical non-polar surface area calculation to facilitate the development of
      an optimum tag for glycan derivatization. The compatibility and advantages of
      this method are demonstrated by cleaving and derivatizing N-linked glycans from
      human plasma proteins. The ESI-MS signal for the tagged glycans are shown to be
      significantly more abundant, and the detection of negatively charged sialylated
      glycans is enhanced.

PMID- 21953185
TI  - Improving liquid chromatography-mass spectrometry sensitivity using a subambient
      pressure ionization with nanoelectrospray (SPIN) interface.
AB  - In this work, the subambient pressure ionization with nanoelectrospray (SPIN) ion
      source and interface, which operates at ~15-30 Torr, is demonstrated to be
      compatible with gradient reversed-phase liquid chromatography-MS applications,
      exemplified here with the analysis of complex samples (a protein tryptic digest
      and a whole cell lysate). A low liquid chromatographic flow rate (100-400 nL/min)
      allowed stable electrospray to be established while avoiding electrical
      breakdown. Efforts to increase the operating pressure of the SPIN source relative
      to previously reported designs prevented solvent freezing and enhanced charged
      cluster/droplet desolvation. A 5- to 12-fold improvement in sensitivity relative
      to a conventional atmospheric pressure nanoelectrospray ionization (ESI) source
      was obtained for detected peptides.

PMID- 21953186
TI  - Distinctive glycerophospholipid profiles of human seminoma and adjacent normal
      tissues by desorption electrospray ionization imaging mass spectrometry.
AB  - Desorption electrospray ionization mass spectrometry (DESI-MS) has been
      successfully used to discriminate between normal and cancerous human tissue from
      different anatomical sites. On the basis of this, DESI-MS imaging was used to
      characterize human seminoma and adjacent normal tissue. Seminoma and adjacent
      normal paired human tissue sections (40 tissues) from 15 patients undergoing
      radical orchiectomy were flash frozen in liquid nitrogen and sectioned to 15 MUm
      thickness and thaw mounted to glass slides. The entire sample was two
      dimensionally analyzed by the charged solvent spray to form a molecular image of
      the biological tissue. DESI-MS images were compared with formalin-fixed,
      hematoxylin and eosin (H&E) stained slides of the same material. Increased signal
      intensity was detected for two seminolipids [seminolipid (16:0/16:0) and
      seminolipid (30:0)] in the normal tubule testis tissue; these compounds were
      undetectable in seminoma tissue, as well as from the surrounding fat, muscle, and
      blood vessels. A glycerophosphoinositol [PI(18:0/20:4)] was also found at
      increased intensity in the normal testes tubule tissue when compared with
      seminoma tissue. Ascorbic acid (i.e., vitamin C) was found at increased amounts
      in seminoma tissue when compared with normal tissue. DESI-MS analysis was
      successfully used to visualize the location of several types of molecules across
      human seminoma and normal tissues. Discrimination between seminoma and adjacent
      normal testes tubules was achieved on the basis of the spatial distributions and
      varying intensities of particular lipid species as well as ascorbic acid. The
      increased presence of ascorbic acid within seminoma compared with normal
      seminiferous tubules was previously unknown.

PMID- 21953187
TI  - Trapping radial electric field optimization in compensated FTICR cells.
AB  - Herein, we present the theoretical and experimental study of the recently
      introduced FTICR cell designs. We developed an approach that determines the
      electric field inside the cell, based on the measurement of calibration
      coefficients as a function of post-excitation radius and other conditions. Using
      the radial electric field divided by radius (E(r)/r) as a criterion of the cell
      harmonization, we compare the compensated cell approach with alternative designs
      and discuss practical implications of the cell compensation.

PMID- 21953188
TI  - A novel 9.4 tesla FTICR mass spectrometer with improved sensitivity, mass
      resolution, and mass range.
AB  - Fourier transform ion cyclotron resonance (FTICR) mass spectrometry provides
      unparalleled mass measurement accuracy and resolving power. However, propagation
      of the technique into new analytical fields requires continued advances in
      instrument speed and sensitivity. Here, we describe a substantial redesign of our
      custom-built 9.4 tesla FTICR mass spectrometer that improves sensitivity,
      acquisition speed, and provides an optimized platform for future instrumentation
      development. The instrument was designed around custom vacuum chambers for
      improved ion optical alignment, minimized distance from the external ion trap to
      magnetic field center, and high conductance for effective differential pumping.
      The length of the transfer optics is 30% shorter than the prior system, for
      reduced time-of-flight mass discrimination and increased ion transmission and
      trapping efficiency at the ICR cell. The ICR cell, electrical vacuum
      feedthroughs, and cabling have been improved to reduce the detection circuit
      capacitance (and improve detection sensitivity) 2-fold. The design simplifies
      access to the ICR cell, and the modular vacuum flange accommodates new ICR cell
      technology, including linearized excitation, high surface area detection, and
      tunable electrostatic trapping potential.

PMID- 21953189
TI  - Infrared laser ablation sample transfer for MALDI and electrospray.
AB  - We have used an infrared laser to ablate materials under ambient conditions that
      were captured in solvent droplets. The droplets were either deposited on a MALDI
      target for off-line analysis by MALDI time-of-flight mass spectrometry or flow
      injected into a nanoelectrospray source of an ion trap mass spectrometer. An
      infrared optical parametric oscillator (OPO) laser system at 2.94 MUm wavelength
      and approximately 1 mJ pulse energy was focused onto samples for ablation at
      atmospheric pressure. The ablated material was captured in a solvent droplet 1-2
      mm in diameter that was suspended from a silica capillary a few millimeters above
      the sample target. Once the sample was transferred to the droplet by ablation,
      the droplet was deposited on a MALDI target. A saturated matrix solution was
      added to the deposited sample, or in some cases, the suspended capture droplet
      contained the matrix. Peptide and protein standards were used to assess the
      effects of the number of IR laser ablation shots, sample to droplet distance,
      capture droplet size, droplet solvent, and laser pulse energy. Droplet collected
      samples were also injected into a nanoelectrospray source of an ion trap mass
      spectrometer with a 500 nL injection loop. It is estimated that pmol quantities
      of material were transferred to the droplet with an efficiency of approximately
      1%. The direct analysis of biological fluids for off-line MALDI and electrospray
      was demonstrated with blood, milk, and egg. The implications of this IR ablation
      sample transfer approach for ambient imaging are discussed.

PMID- 21953190
TI  - Mass spectrometry-based quantification of pseudouridine in RNA.
AB  - Direct detection of pseudouridine (psi), an isomer of uridine, in RNA is
      challenging. The most popular method requires chemical derivatization using N
      cyclohexyl-N'-beta-(4-methylmorpholinum ethyl) carbodiimide p-tosylate (CMCT)
      followed by radiolabeled primer extension mediated by reverse transcriptase. More
      recently, mass spectrometry (MS)-based approaches for sequence placement of
      pseudouridine in RNA have been developed. Nearly all of these approaches,
      however, only yield qualitative information regarding the presence or absence of
      pseudouridine in a given RNA population. Here, we have extended a previously
      developed liquid chromatography tandem mass spectrometry (LC-MS/MS) method to
      enable both the qualitative and quantitative analysis of pseudouridine.
      Quantitative selected reaction monitoring (SRM) assays were developed using
      synthetic oligonucleotides, with or without pseudouridine, and the results
      yielded a linear relationship between the ion abundance of the pseudouridine
      specific fragment ion and the amount of pseudouridine-containing oligonucleotide
      present in the original sample. Using this quantitative SRM assay, the extent of
      pseudouridine hypomodification in the conserved T-loop of tRNA isolated from two
      different Escherichia coli strains was established.

PMID- 21953191
TI  - Software lock mass by two-dimensional minimization of peptide mass errors.
AB  - Mass accuracy is a key parameter in proteomic experiments, improving specificity,
      and success rates of peptide identification. Advances in instrumentation now make
      it possible to routinely obtain high resolution data in proteomic experiments. To
      compensate for drifts in instrument calibration, a compound of known mass is
      often employed. This 'lock mass' provides an internal mass standard in every
      spectrum. Here we take advantage of the complexity of typical peptide mixtures in
      proteomics to eliminate the requirement for a physical lock mass. We find that
      mass scale drift is primarily a function of the m/z and the elution time
      dimensions. Using a subset of high confidence peptide identifications from a
      first pass database search, which effectively substitute for the lock mass, we
      set up a global mathematical minimization problem. We perform a simultaneous fit
      in two dimensions using a function whose parameterization is automatically
      adjusted to the complexity of the analyzed peptide mixture. Mass deviation of the
      high confidence peptides from their calculated values is then minimized globally
      as a function of both m/z value and elution time. The resulting recalibration
      function performs equal or better than adding a lock mass from laboratory air to
      LTQ-Orbitrap spectra. This 'software lock mass' drastically improves mass
      accuracy compared with mass measurement without lock mass (up to 10-fold), with
      none of the experimental cost of a physical lock mass, and it integrated into the
      freely available MaxQuant analysis pipeline ( www.maxquant.org ).

PMID- 21953192
TI  - QMS in the third stability zone with a transverse magnetic field applied.
AB  - We report here a study using a quadrupole mass spectrometer (QMS) in which a
      static magnetic field is applied transversely to the body of the mass filter
      operating in stability zone 3. Significant improvement in QMS performance was
      obtained under certain magnetic field conditions, and these have been explained
      in terms of our theoretical model. The theoretical approach assumed in the model
      is that the QMS contains hyperbolic rods as electrodes and that the magnetic
      field acts over the full length of the mass filter assembly. Our latest analysis
      also predicts for what values of operating parameters an enhancement of the
      quadrupole resolution is achieved when a transverse magnetic field is applied.
      The model predicts instrument resolution R > 5000 for Ar with a 100 mm long mass
      filter and R > 3500 for a HT and D(2) mixture with a 200 mm long mass filter via
      application of a transverse magnetic field.

PMID- 21953193
TI  - Characterization of the ion beam focusing in a mass spectrometer using an
      IonCCDTM detector.
AB  - A position sensitive pixel-based detector array, referred to as the IonCCD, has
      been employed to characterize the ion optics and ion beam focusing in a custom
      built mass spectrometer designed for soft and reactive landing of mass-selected
      ions onto surfaces. The IonCCD was placed at several stages along the path of the
      ion beam to determine the focusing capabilities of the various ion optics, which
      include an electrodynamic ion funnel, two radiofrequency (rf)-only collision
      quadrupoles, a mass resolving quadrupole, a quadrupole bender, and two einzel
      lens assemblies. The focusing capabilities of the rf-only collision quadrupoles
      and einzel lenses are demonstrated by large decreases in the diameter of the ion
      beam. In contrast, the mass resolving quadrupole is shown to significantly
      defocus the mass-selected ion beam resulting in an expansion of the measured ion
      beam diameter. Combined with SIMION simulations, we demonstrate that the IonCCD
      can identify minor errors in the alignment of charged-particle optics that result
      in erratic trajectories and significant deflections of the ion beam. This
      information may be used to facilitate the design, assembly, and maintenance of
      custom-built mass spectrometry instrumentation.

PMID- 21953194
TI  - Aliphatic hydrocarbon spectra by helium ionization mass spectrometry (HIMS) on a
      modified atmospheric-pressure source designed for electrospray ionization.
AB  - Chemical-ionization techniques that use metastable species to ionize analytes
      traditionally use a flat pin or a sharp solid needle onto which the high
      potential needed to generate the discharge plasma is applied. We report here that
      direct analysis of samples containing volatile and semivolatile compounds,
      including saturated and unsaturated aliphatic hydrocarbons, can be achieved on
      any electrospray-ionization mass spectrometer by passing helium though the sample
      delivery metal capillary held at a high potential. In the helium plasma
      ionization source (HPIS) described here, the typical helium flow required (about
      20-30 mL/min), was significantly lower than that needed for other helium
      ionization sources. By this procedure, positive ions were generated by nominal
      hydride ion removal from molecules emanating from heated saturated hydrocarbons
      as large as tetratetracontane (C(44)H(90)), at capillary voltages ranging from
      2.0 to 4.0 kV. Unsaturated hydrocarbons, on the other hand, underwent facile
      protonation under much lower capillary voltages (0.9 to 2.0 kV). Although
      saturated and monounsaturated hydrocarbons bearing the same number of carbon
      atoms generate ions of the same m/z ratio, a gas-phase deuterium exchange method
      is described to ascertain the identity of these isomeric ions originating from
      either protonation or hydride abstraction mechanisms. Moreover, mass
      spectrometric results obtained by exposing unsaturated hydrocarbons to D(2)O
      vapor in an HPIS-MS instrument confirmed that the proton donor for ionization of
      unsaturated hydrocarbons is protonated water.

PMID- 21953195
TI  - Depth profiling (ICP-MS) study of trace metal 'grains' in solid asphaltenes.
AB  - Knowledge of trace metal 'grains' in asphaltenes could play a significant role in
      enhancing refining and processing of crudes and also in providing useful
      information on mechanistic and migratory features linked to asphaltenes. These
      metals originate directly from interaction of oils with source-rock, mineral
      matter, and formation water and their accumulation in asphaltene matrices could
      vary from oil well to oil well. Suitable asphaltene samples were subjected to
      high-performance ICP-MS laser depth profiling (213 nm) to depths of 50 MUm at 5
      MUm intervals. The study was conducted in the absence of standardization and
      characteristic intensities originating from the metals of interest were measured.
      Ten metal profiles were investigated (Na, Mg, Al, Mn, Fe, Zn, Sr, Pb, V, and Ni).
      The experimental results showed non-uniform distribution of trace metals and
      identified areas where such metals agglomerate. The data suggested that certain
      chemical and physical conditions within the structure of asphaltenes are
      favorable for metal 'grain' formation at specific points. The exact mechanism for
      this behavior is not clear at this stage, and has considerable scope for future
      studies, including mathematical modeling simulations of asphaltenes. We also
      found that solid asphaltenes could be a useful forerunner of scale formation.

PMID- 21953196
TI  - Reagent precoated targets for rapid in-tissue derivatization of the anti
      tuberculosis drug isoniazid followed by MALDI imaging mass spectrometry.
AB  - Isoniazid (INH) is an important component of front-line anti-tuberculosis therapy
      with good serum pharmacokinetics but unknown ability to penetrate tuberculous
      lesions. However, endogenous background interferences hinder our ability to
      directly analyze INH in tissues. Chemical derivatization has been successfully
      used to measure isoniazid directly from tissue samples using matrix-assisted
      laser desorption/ionization (MALDI) imaging mass spectrometry (IMS). MALDI
      targets were pretreated with trans-cinnamaldehyde (CA) prior to mounting tissue
      slices. Isoniazid present in the tissues was efficiently derivatized and the INH
      CA product measured by MS/MS. Precoating of MALDI targets allows the tissues to
      be directly thaw-mounted and derivatized, thus simplifying the preparation. A
      time-course series of tissues from tuberculosis infected/INH dosed animals were
      assayed and the MALDI MS/MS response correlates well with the amount of INH
      determined to be in the tissues by high-performance liquid chromatography (HPLC)
      MS/MS.

PMID- 21953197
TI  - Tandem mass spectrometry measurement of the collision products of carbamate
      anions derived from CO2 capture sorbents: paving the way for accurate
      quantitation.
AB  - The reaction between CO(2) and aqueous amines to produce a charged carbamate
      product plays a crucial role in post-combustion capture chemistry when primary
      and secondary amines are used. In this paper, we report the low energy negative
      ion CID results for several anionic carbamates derived from primary and secondary
      amines commonly used as post-combustion capture solvents. The study was performed
      using the modern equivalent of a triple quadrupole instrument equipped with a T
      wave collision cell. Deuterium labeling of 2-aminoethanol (1,1,2,2,-d(4)-2
      aminoethanol) and computations at the M06-2X/6-311++G(d,p) level were used to
      confirm the identity of the fragmentation products for 2-hydroxyethylcarbamate
      (derived from 2-aminoethanol), in particular the ions CN(-), NCO(-) and facile
      neutral losses of CO(2) and water; there is precedent for the latter in condensed
      phase isocyanate chemistry. The fragmentations of 2-hydroxyethylcarbamate were
      generalized for carbamate anions derived from other capture amines, including
      ethylenediamine, diethanolamine, and piperazine. We also report unequivocal
      evidence for the existence of carbamate anions derived from sterically hindered
      amines (Tris(2-hydroxymethyl)aminomethane and 2-methyl-2-aminopropanol). For the
      suite of carbamates investigated, diagnostic losses include the decarboxylation
      product (-CO(2), 44 mass units), loss of 46 mass units and the fragments NCO(-)
      (m/z 42) and CN(-) (m/z 26). We also report low energy CID results for the
      dicarbamate dianion ((-)O(2)CNHC(2)H(4)NHCO(2)(-)) commonly encountered in CO(2)
      capture solution utilizing ethylenediamine. Finally, we demonstrate a promising
      ion chromatography-MS based procedure for the separation and quantitation of
      aqueous anionic carbamates, which is based on the reported CID findings. The
      availability of accurate quantitation methods for ionic CO(2) capture products
      could lead to dynamic operational tuning of CO(2) capture-plants and, thus, cost
      savings via real-time manipulation of solvent regeneration energies.

PMID- 21953198
TI  - Mapping a noncovalent protein-peptide interface by top-down FTICR mass
      spectrometry using electron capture dissociation.
AB  - Noncovalent protein-ligand and protein-protein complexes are readily detected
      using electrospray ionization mass spectrometry (ESI MS). Furthermore, recent
      reports have demonstrated that careful use of electron capture dissociation (ECD)
      fragmentation allows covalent backbone bonds of protein complexes to be
      dissociated without disruption of noncovalent protein-ligand interactions. In
      this way the site of protein-ligand interfaces can be identified. To date,
      protein-ligand complexes, which have proven tractable to this technique, have
      been mediated by ionic electrostatic interactions, i.e., ion pair interactions or
      salt bridging. Here we extend this methodology by applying ECD to study a protein
      peptide complex that contains no electrostatics interactions. We analyzed the
      complex between the 21 kDa p53-inhibitor protein anterior gradient-2 and its
      hexapeptide binding ligand (PTTIYY). ECD fragmentation of the 1:1 complex occurs
      with retention of protein-peptide binding and analysis of the resulting fragments
      allows the binding interface to be localized to a C-terminal region between
      residues 109 and 175. These finding are supported by a solution-phase competition
      assay, which implicates the region between residues 108 and 122 within AGR2 as
      the PTTIYY binding interface. Our study expands previous findings by
      demonstrating that top-down ECD mass spectrometry can be used to determine
      directly the sites of peptide-protein interfaces. This highlights the growing
      potential of using ECD and related top-down fragmentation techniques for
      interrogation of protein-protein interfaces.

PMID- 21953199
TI  - Effects of peptide backbone amide-to-ester bond substitution on the cleavage
      frequency in electron capture dissociation and collision-activated dissociation.
AB  - Probing the mechanism of electron capture dissociation on variously modified
      model peptide polycations has resulted in discovering many ways to prevent or
      reduce N-Calpha bond fragmentation. Here we report on a rare finding of how to
      increase the backbone bond dissociation rate. In a number of model peptides,
      amide-to-ester backbone bond substitution increased the frequency of O-Calpha
      bond cleavage (an analogue of N-Calpha bonds in normal peptides) by several
      times, at the expense of reduced frequency of cleavages of the neighboring N
      Calpha bonds. In contrast, the ester linkage was only marginally broken in
      collisional dissociation. These results further highlight the complementarity of
      the reaction mechanisms in electron capture dissociation (ECD) and collision
      activated dissociation (CAD). It is proposed that the effects of amide-to-ester
      bond substitution on fragmentation are mainly due to the differences in product
      ion stability (ECD, CAD) as well as proton affinity (CAD). This proposal is
      substantiated by calculations using density functional theory. The implications
      of these results in relation to the current understanding of the mechanisms of
      electron capture dissociation and electron transfer dissociation are discussed.

PMID- 21953200
TI  - Differentiation of alpha- or beta-aspartic isomers in the heptapeptides by the
      fragments of [M + Na]+ using ion trap tandem mass spectrometry.
AB  - Electrospray ionization coupled with low energy collision induced dissociation
      (CID) in an ion trap mass spectrometer was used to examine the fragmentation
      patterns of the [M + Na](+) of eight pairs of heptapeptides containing alpha- or
      beta-Asp residues in second and sixth amino acid positions, respectively.
      Selective cleavages at the peptide backbone C-terminal to two Asp residues were
      observed, which generated a series of C-terminal y(5) ions and N-terminal b(6)
      ions. Two typical ions: [y5 + Na - H]+ and [b6 + Na + OH]+, produced by alpha-Asp
      containing peptides were noted to be much more abundant than those of the
      peptides with beta-Asp, which could be used for distinction of the isomers in
      Asp2 and Asp6, respectively. In addition, a series of internal ions generated by
      simultaneous cleavages at Asp residues were detected. Competitive reactions of
      carboxylic groups occurred between Asp6 side chain and C-terminus. Formation
      mechanisms of most product ions are proposed. The results obtained in this work
      are significant since low energy CID has been demonstrated to be effective for
      the distinction of Asp isomers.

PMID- 21953201
TI  - Differentiation of compact and extended conformations of di-ubiquitin conjugates
      with lysine-specific isopeptide linkages by ion mobility-mass spectrometry.
AB  - Modification of ubiquitin, a key cellular regulatory polypeptide of 76 amino
      acids, to polyubiquitin conjugates by lysine-specific isopeptide linkage at one
      of its seven lysine residues has been recognized as a central pathway determining
      its biochemical properties and cellular functions. Structural details and
      differences of distinct lysine-isopeptidyl ubiquitin conjugates that reflect
      their different functions and reactivities, however, are only partially
      understood. Ion mobility spectrometry (IMS) combined with mass spectrometry (MS)
      has recently emerged as a powerful tool for probing conformations and topology
      involved in protein interactions by an electric field-driven separation of
      polypeptide ions through a drift gas. Here we report the conformational
      characterization and differentiation of Lys63- and Lys48-linked ubiquitin
      conjugates by IMS-MS. Lys63- and Lys48-linked di-ubiquitin conjugates were
      prepared by recombinant bacterial expression and by chemical synthesis using a
      specific chemical ligation strategy, and characterized by high-resolution Fourier
      transform ion cyclotron resonance mass spectrometry, circular dichroism
      spectroscopy, and molecular modeling. IMS-MS was found to be an effective tool
      for the identification of structural differences of ubiquitin complexes in the
      gas phase. The comparison of collision cross-sections of Lys63- and Lys48-linked
      di-ubiquitin conjugates showed a more elongated conformation of Lys63-linked di
      ubiquitin. In contrast, the Lys48-linked di-ubiquitin conjugate showed a more
      compact conformation. The IMS-MS results are consistent with published structural
      data and a comparative molecular modeling study of the Lys63- and Lys48-linked
      conjugates. The results presented here suggest IMS techniques can provide
      information that complements MS measurements in differentiating higher-order
      polyubiquitins and other isomeric protein linkages.

PMID- 21953202
TI  - An efficient and inexpensive refrigerated LC system for H/D exchange mass
      spectrometry.
AB  - Loss of deuterium label during the LC step in amide hydrogen/deuterium exchange
      mass spectrometry (H/D-MS) is minimized by maintaining an acidic mobile phase pH
      and low temperature (pH 2.5, 0  degrees C). Here we detail the construction and
      performance of a low-cost, thermoelectrically refrigerated enclosure to house
      high-performance liquid chromatography (HPLC) components and cool mobile phases.
      Small volume heat exchangers rapidly decrease mobile phase temperature and keep
      the temperature stable to +/-0.2  degrees C. Using a superficially porous
      reversed-phase column, we obtained excellent chromatographic performance in the
      separation of peptides with a median peak width of 4.4 s. Average deuterium
      recovery was 80.2% with an average relative precision of 0.91%.

PMID- 21953203
TI  - Nanosecond electric pulses cause mitochondrial membrane permeabilization in
      Jurkat cells.
AB  - Nanosecond, high-voltage electric pulses (nsEP) induce permeabilization of the
      plasma membrane and the membranes of cell organelles, leading to various
      responses in cells including cytochrome c release from mitochondria and caspase
      activation associated with apoptosis. We report here evidence for nsEP-induced
      permeabilization of mitochondrial membranes in living cells. Using three
      different methods with fluorescence indicators-rhodamine 123 (R123), tetramethyl
      rhodamine ethyl ester (TMRE), and cobalt-quenched calcein-we have shown that
      multiple nsEP (five pulses or more, 4 ns duration, 10 MV/m, 1 kHz repetition
      rate) cause an increase of the inner mitochondrial membrane permeability and an
      associated loss of mitochondrial membrane potential. These effects could be a
      consequence of nsEP permeabilization of the inner mitochondrial membrane or the
      activation of mitochondrial membrane permeability transition pores. Plasma
      membrane permeabilization (YO-PRO-1 influx) was detected in addition to
      mitochondrial membrane permeabilization.

PMID- 21953204
TI  - Marginal association measures for clustered data.
AB  - The use of correlation coefficients in measuring the association between two
      continuous variables is common, but regular methods of calculating correlations
      have not been extended to the clustered data framework. For clustered data in
      which observations within a cluster may be correlated, regular inferential
      procedures for calculating marginal association between two variables can be
      biased. This is particularly true for data in which the number of observations in
      a given cluster is informative for the association being measured. In this paper,
      we apply the principle of inverse cluster size reweighting to develop estimators
      of marginal correlation that remain valid in the clustered data framework when
      cluster size is informative for the correlation being measured. These
      correlations are derived as analogs to regular correlation estimators for
      continuous, independent data, namely, Pearson's rho and Kendall's tau. We present
      the results of a simple simulation study demonstrating the appropriateness of our
      proposed estimators and the inherent bias of other inferential procedures for
      clustered data. We illustrate their use through an application to data from
      patients with incomplete spinal cord injury in the U.S.A.

PMID- 21953205
TI  - Development of responder definitions for fibromyalgia clinical trials.
AB  - OBJECTIVE: To develop responder definitions for fibromyalgia (FM) clinical trials
      using key symptom and function domains. METHODS: Twenty-four candidate responder
      definitions were developed by expert consensus and were evaluated in 12
      randomized, placebo-controlled trials of 4 medications for the treatment of FM.
      For each definition, the treatment effects of the medication compared with
      placebo were analyzed using Cochran-Mantel-Haenszel tests or chi-square tests. A
      meta-analysis of the pooled results for the 4 medications established risk ratios
      to determine the definitions that best favored medication over placebo. RESULTS:
      Two definitions performed best in the analyses. Both definitions included >=30%
      reduction in pain and >=10% improvement in physical function. The definitions
      differed in that one (>=30% improvement in FM [FM30] short version) included
      >=30% improvement in sleep or fatigue, and the other (FM30 long version) required
      >=30% improvement in 2 of the following symptoms: sleep, fatigue, depression,
      anxiety, or cognition. In the analysis of both versions, the response rate was
      >=15% for each medication and was significantly greater compared with placebo.
      The risk ratio favoring drug over placebo in the pooled analysis for FM30 version
      3 (short version) was 1.50 (95% confidence interval [95% CI] 1.24-1.82; P <=
      0.0001); the risk ratio for FM30 version 6 (long version) was 1.60 (95% CI 1.31
      1.96; P <= 0.00001). CONCLUSION: Among the 24 responder definitions tested, 2
      were identified as most sensitive in identifying response to treatment. The
      identification of responder definitions for FM clinical trials that include
      assessments of key symptom and function domains may improve the sensitivity of
      clinical trials to identify meaningful improvements, leading to improved
      management of FM.

PMID- 21953206
TI  - Reproducibility of MUNIX in patients with amyotrophic lateral sclerosis.
AB  - INTRODUCTION: In this study we investigated the reproducibility of motor unit
      number index (MUNIX) in patients with amyotrophic lateral sclerosis (ALS).
      METHODS: MUNIX was recorded in patients with ALS. Studies were performed in 18
      thenar and 18 hypothenar muscles by two operators. The reproducibility was
      assessed using mean MUNIX values, linear regression, correlation coefficient, and
      coefficient of variation (COV) in individual studies. RESULTS: The mean values
      showed no significant difference. The linear regression showed a strong
      correlation. Most patients had low COV. A high COV was seen when MUNIX was very
      low. The COV was higher in thenar than in hypothenar muscles. CONCLUSIONS: MUNIX
      has very good reproducibility in ALS patients. COV may exaggerate interoperator
      variation when MUNIX is very low. The higher variability in the thenar muscle is
      also due to variability in compound muscle action potential amplitude. Although
      both muscles show good reproducibility, the hypothenar is better suited for
      serial studies in individual patients.

PMID- 21953207
TI  - Characterization of heterotic quantitative trait loci in maize by evaluation of
      near-isogenic lines and their crosses at two competition levels.
AB  - In a previous study on a maize (Zea mays L.) population of recombinant inbreds
      derived from B73 * H99, we identified several quantitative trait loci (QTL) for
      agronomic traits with high dominance-additive ratio. Then, for four of these QTL,
      we developed families of near-isogenic lines (NILs) homozygous either for the QTL
      allele from B73 (BB) or from H99 (HH); for two of these QTL, the NILs' families
      were produced in two different genetic backgrounds. The present study was
      conducted to: (1) characterize these QTL for agronomic traits and (2) verify
      whether their effects were influenced by the genetic background, inbreeding level
      and plant density (PD). The six NILs' families were tested across 3 years and in
      three experiments at different inbreeding levels as NILs per se and their
      reciprocal crosses (Experiment 1), NILs crossed to related inbreds B73 and H99
      (Experiment 2) and NILs crossed to four unrelated inbreds (Experiment 3).
      Experiment 2 was conducted at two PDs (4.5 and 9.0 plants m(-2)). Results of
      Experiments 1 and 2 confirmed previous findings as to QTL effects, with dominance
      additive ratio superior to 1 for several traits; as a tendency, dominance effects
      were more pronounced in Experiment 1. The QTL effects were also confirmed in
      Experiment 3. The interactions involving QTL effects, families and PD were
      generally negligible, suggesting a certain stability of the QTL. Results
      emphasize the importance of dominance effects for these QTL, suggesting that they
      might deserve further studies, using the NILs' families and their crosses as base
      materials.

PMID- 21953208
TI  - Molecular mapping of resistance gene to English grain aphid (Sitobion avenae F.)
      in Triticum durum wheat line C273.
AB  - The English grain aphid, Sitobion avenae (Fabricius), is one of the most
      important insect pests causing substantial yield losses in wheat production in
      China and other grain-growing areas in the world. The efficient utilization of
      wheat genes for resistance to English grain aphid (EGA) provides an efficient,
      economic and environmentally sound approach to reduce the yield losses. In the
      present study, the wheat line C273 (Triticum durum AABB, 2n = 4x = 28), is
      resistant to EGA in greenhouse and field tests. To identify the resistance gene,
      designated RA-1 temporarily, C273 was crossed with susceptible genotype Poland
      305 (T. polonicum, AABB, 2n = 4x = 28). The F(1), F(2) and F(2:3) lines were
      tested with EGA in the field and greenhouse. The results indicated that RA-1 is a
      single dominant gene, closely linked to the microsatellite markers (SSR) Xwmc179,
      Xwmc553 and Xwmc201 on chromosome 6AL at genetic distances of 3.47, 4.73 and 7.57
      cM, respectively. The three SSR markers will be valuable in marker-assisted
      selection for resistance to EGA as well as for cloning this gene in the future.

PMID- 21953209
TI  - Pancreatic arteriovenous malformation involving the duodenum embolized with
      ethylene-vinyl alcohol copolymer (Onyx).
AB  - Arteriovenous malformation (AVM) of the pancreas is a rare condition. Most
      patients are asymptomatic or alternatively may present with a wide spectrum of
      symptoms. Traditionally, surgery has been considered the treatment of choice;
      however, alternative approaches, such as transcatheter embolization (TAE), may be
      proposed. We report a case of a 48-year-old man with a pancreatic head AVM,
      presenting with upper abdominal pain and slight anemia. The patient refused
      surgery and underwent TAE by means of ethylene-vinyl alcohol copolymer (EVOH). At
      3 months follow-up, the patient was able to eat regularly, with no residual pain
      and no signs of anemia.

PMID- 21953210
TI  - Correction of head movements in positron emission tomography using point source
      tracking system: a simulation study.
AB  - AIM: The motion of the head during brain positron emission tomography (PET)
      acquisitions has been identified as a source of artifact in the reconstructed
      image. In this study, a method is described to develop an image-based motion
      correction technique for correcting the post-acquisition data without using
      external optical motion-tracking system such as POLARIS. METHOD: In this
      technique, GATE has been used to simulate PET brain scan using point sources
      mounted around the head to accurately monitor the position of the head during the
      time frames. RESULT: The measurement of head motion in each frame showed a
      transformation in the image frame matrix, resulting in a fully corrected data
      set. CONCLUSION: Using different kinds of phantoms and motions, the accuracy of
      the correction method is tested and its applicability to experimental studies is
      demonstrated as well.

PMID- 21953211
TI  - Cortical-limbic regions modulate depression and anxiety factors in functional
      dyspepsia: a PET-CT study.
AB  - OBJECTIVE: To observe some specific brain areas or cerebral functional network
      participating in the modulation of depression and anxiety factors in functional
      dyspepsia (FD) patients by detecting cerebral glucose metabolism (CGM) in
      fluorine-18 fluorodeoxyglucose ((18)F-FDG) positron emission tomography-computed
      tomography (PET-CT) scans. METHODS: Eight FD patients with depression and anxiety
      (DA-FD group) and eight FD patients without depression and anxiety (non-DA-FD
      group) were recruited and evaluated by the Nepean Dyspepsia Index (NDI) and
      Dyspepsia Symptom Scores (DSS). Cerebral (18)F-FDG PET-CT scans were performed on
      the DA-FD group and non-DA-FD group, respectively. The differences in CGM between
      the two groups were analyzed with SPM2. RESULTS: Extensive changes in the CGM
      signals were observed in the cerebral cortex and limbic system of FD patients
      with depression and anxiety. Compared to non-DA-FD patients, DA-FD patients
      showed a higher glucose metabolism in the right postcentral gyrus (BA 1 and 5),
      inferior frontal gyrus (BA 45), superior temporal gyrus (BA 22), middle temporal
      gyrus (BA 22), inferior parietal lobule (BA 40), lingual gyrus (BA 18) and the
      left middle occipital gyrus (BA 37), as well as the limbic system including the
      left thalamus, lateral globus pallidus, parahippocampal gyrus (BA 35), right
      insular cortex (BA 13) and parahippocampal gyrus (BA 18); a lower glucose
      metabolism was presented in the left middle cingulated gyrus (BA 24), the right
      superior frontal gyrus (BA 6), the medial frontal gyrus (BA 6) and middle
      temporal gyrus (BA 21). CONCLUSION: An extensive cortical-limbic brain network
      might modulate the procession of FD patients with depression and anxiety factors.

PMID- 21953212
TI  - FDG-avid sclerotic bone metastases in breast cancer patients: a PET/CT case
      series.
AB  - Distant metastases from breast cancer most frequently occur in the skeleton.
      Although 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), with or
      without computed tomography (CT), is superior to bone scintigraphy for the
      detection of osteolytic bone metastases, it has been reported that sclerotic bone
      metastases frequently show no or only a low degree of FDG uptake on PET and
      PET/CT. Since both lytic and sclerotic metastases can occur in breast cancer
      patients, bone scintigraphy may remain of additional value in these patients. In
      this case series, we describe four breast cancer patients in whom FDG PET/CT has
      clearly visualized sclerotic bone metastases because of increased FDG uptake. Not
      so much the type of metastasis (sclerotic or lytic), but possibly the
      characteristics of the primary tumor or treatments prior to the FDG PET/CT scan
      might influence the degree of FDG uptake of bone metastases. The ability to
      detect sclerotic bone metastases based on increased FDG uptake supports the use
      of FDG PET/CT as a staging procedure in breast cancer patients, but knowledge of
      factors determining the visibility of bone metastases with FDG PET/CT is crucial.

PMID- 21953213
TI  - Efficacy of neoadjuvant therapy with trastuzumab concurrent with anthracycline-
      and nonanthracycline-based regimens for HER2-positive breast cancer.
AB  - BACKGROUND: The aim of this study was to evaluate the pathologic complete
      response (pCR) rates and relapse-free survival (RFS) and overall survival (OS) of
      patients receiving neoadjuvant systemic therapy (NST) with trastuzumab in
      combination with an anthracycline- or nonanthracycline-based regimen. METHODS: In
      this retrospective nonrandomized study, the authors reviewed records of 300
      patients with HER2-positive breast cancer treated with either sequential
      paclitaxel and trastuzumab and FEC75 in combination with trastuzumab (PH-FECH) or
      docetaxel, carboplatin, and trastuzumab (TCH). The Kaplan-Meier product-limit
      method was used to estimate RFS and OS rates. Logistic regression models and Cox
      proportional hazards models were fit to determine the associations between NST,
      pCR, and survival. RESULTS: There was no significant difference in the decline in
      cardiac ejection fraction; however, patients who received PH-FECH had fewer
      cardiac comorbidities at baseline (P = .002). pCR rates were 60.6% and 43.3% for
      patients who received PH-FECH (n = 235) and TCH (n = 65), respectively (P =
      .016). Patients who received PH-FECH were 1.45 times more likely to have a pCR
      (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.06-1.98; P = .02). Three
      year RFS rates were 93% and 71% (P < .001), and 3-year OS rates were 96% and 86%
      (P = .008) for patients who received PH-FECH and TCH, respectively. Patients who
      received PH-FECH had a lower risk of recurrence (hazard ratio [HR], 0.27; 95% CI,
      0.12-0.60; P = .001) and death (HR, 0.37; 95% CI, 0.12-1.13; P = .08) than those
      treated with TCH. CONCLUSIONS: The type of NST in HER2-positive breast cancer is
      predictive of pCR rate independent of disease and patient characteristics.
      Although TCH is active, PH-FECH shows a higher pCR rate and RFS advantage.

PMID- 21953214
TI  - Cloning and characterization of a bifunctional glycosyl hydrolase from an
      antagonistic Pseudomonas putida strain P3(4).
AB  - A fluorescent pseudomonad strain P3(4) showing chitinolysis on chitinase
      detection agar and antagonism against Fusarium oxysporum f.sp dianthi causing
      vascular wilt of carnation was isolated from pea rhizosphere soil. PCR primers
      specific for glycosyl hydrolase family 5 (GH5) of Pseudomonas putida isolate
      KT2440 amplified a 947 bp fragment of the GH5 gene from P3(4). Cloning of this
      gene into Escherichia coli M15 using an expression vector pQE-30UA and screening
      on chitin and chitosan detection agar identified one positive clone (Pchi(+) ).
      Sequence analysis of the cloned insert revealed an open reading frame of 947
      nucleotides corresponding to a protein of 315 amino acids with a predicted
      molecular mass of 38.0 kDa. The deduced amino acid sequence of the open reading
      frame (gene product/GH) showed 83-84% homology to the GH5 of P. putida strains F1
      and KT2440, respectively. The purified enzyme was homogenous, as examined by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis and was visualized as
      single fluorescent band in native gel assay with 4-methylumbelliferyl-N -acetyl
      beta;-D-glucosaminide and glycol chitosan, respectively. For hydrolysis of 4
      nitrophenyl-N -acetyl-beta;-D-glucosaminide (pNP-(GlcNAc) and colloidal chitosan,
      the enzyme had an optimal temperature of 40  degrees C, and was stable within the
      temperature range of 10  degrees C to 40  degrees C. The enzyme showed an optimal
      pH of 3.5, with maximum stabilities at 5.0 and 5.5 for hydrolysis of pNP-(GlcNAc)
      and colloidal chitosan, respectively. Fe(3+) and Cu(2+) stimulated chitinase and
      chitosanase activities by 74.2 and 51.4%, respectively. The purified GH displayed
      70 and 45% inhibition of spore germination of the pathogenic fungi, Fusarium
      oxysporum f.sp. dianthi and Alternaria solani, respectively.

PMID- 21953215
TI  - Joint damage in rheumatoid arthritis progresses in remission according to the
      Disease Activity Score in 28 joints and is driven by residual swollen joints.
AB  - OBJECTIVE: Remission has been defined as the ultimate target for patients with
      rheumatoid arthritis. The Disease Activity Score in 28 joints (DAS28) has been
      criticized for the amount of disease activity that remains in patients despite
      their achieving DAS28 remission. This study was undertaken to investigate the
      significance of residual inflammation in remission in relation to radiographic
      progression. METHODS: We pooled 1-year clinical data, kindly provided by the
      respective sponsors, on 864 patients in methotrexate monotherapy arms of recent
      pivotal trials. We identified patients who had attained persistent DAS28
      remission from month 6 through month 12 (a DAS28(6-12)  of <2.6). Among these
      patients we then assessed radiographic progression in total Sharp/van der Heijde
      scores (SHS) from baseline to 12 months between those with residual joint
      swelling (defined as a swollen joint count from month 6 through month 12 [SJC(6
      12) ] of >=2) and those without residual joint swelling (defined as an SJC(6-12) 
      of <2). RESULTS: One hundred fourteen patients (13.2%) achieved a DAS28(6-12)  of
      <2.6, of whom those without residual joint swelling (n = 92, 80.7%) had less
      radiographic progression over 1 year than those with residual joint swelling (n =
      22, 19.3%) (mean +/- SD SHS progression 0.2 +/- 2.6 versus 2.2 +/- 4.2; P =
      0.11). Likewise, the proportion of patients with a total SHS progression of
      >0.5/year was significantly lower among those without joint swelling than among
      those with joint swelling (27.2% versus 50.0%; P = 0.039). DAS28 remitters
      without joint swelling showed progression comparable to that in the total group
      of remitters by the Simplified Disease Activity Index (remission defined as
      <=3.3) and Clinical Disease Activity Index (remission defined as <=2.8), namely,
      0.2 versus -0.07 versus 0.16, respectively (P = 0.66). CONCLUSION: Radiographic
      progression with nonbiologic treatment is minimal only when patients in DAS28
      remission have no persistent residual joint swelling. Under these conditions,
      progression is comparable to that in patients with disease in remission according
      to other disease activity indices.

PMID- 21953217
TI  - The phenology of cherry blossom (Prunus yedoensis "Somei-yoshino") and the
      geographic features contributing to its flowering.
AB  - We investigated relationships between the flowering phenology of Prunus yedoensis
      "Somei-yoshino" (cherry blossom) and the local temperatures in Japan. Our
      observations were carried out across the Okayama Plain, which included Okayama
      City (about 700,000 inhabitants), from the winter of 2008 to the spring of 2009.
      Local air temperature (AT) and the globe temperature (GT) were recorded at the
      tree height. The flowering dates (FDs) of P. yedoensis were earliest in the
      central commercial area (located at the center of the plain), followed by the
      north residential area (further inland), and finally the south residential area
      (seaward). The recorded FDs were related to the period-averaged daily
      maximum/minimum AT and GT, and the phenologically effective AT and GT defined in
      this study. Of these parameters, the phenologically effective GTs correlated most
      with the FDs. Since the GT is determined by AT, solar and infrared radiations,
      and wind speed, our previous result suggests that a combination of these three
      components surrounding the tree is more important for budding and flowering than
      is AT alone. The supposition is supported by the flowering of P. yedoensis being
      the latest at the coastal region of the Okayama Plain where the AT were higher
      than at the inland region, excluding the urban area; it is probably caused by
      stronger winds there than at the other sites.

PMID- 21953216
TI  - Osteopontin, an oxidant stress sensitive cytokine, up-regulates collagen-I via
      integrin alpha(V)beta(3) engagement and PI3K/pAkt/NFkappaB signaling.
AB  - A key feature in the pathogenesis of liver fibrosis is fibrillar Collagen-I
      deposition; yet, mediators that could be key therapeutic targets remain elusive.
      We hypothesized that osteopontin (OPN), an extracellular matrix (ECM) cytokine
      expressed in hepatic stellate cells (HSCs), could drive fibrogenesis by
      modulating the HSC pro-fibrogenic phenotype and Collagen-I expression.
      Recombinant OPN (rOPN) up-regulated Collagen-I protein in primary HSCs in a
      transforming growth factor beta (TGFbeta)-independent fashion, whereas it down
      regulated matrix metalloprotease-13 (MMP13), thus favoring scarring. rOPN
      activated primary HSCs, confirmed by increased alpha-smooth muscle actin
      (alphaSMA) expression and enhanced their invasive and wound-healing potential.
      HSCs isolated from wild-type (WT) mice were more profibrogenic than those from
      OPN knockout (Opn(-/-)) mice and infection of primary HSCs with an Ad-OPN
      increased Collagen-I, indicating correlation between both proteins. OPN induction
      of Collagen-I occurred via integrin alpha(v)beta(3) engagement and activation of
      the phosphoinositide 3-kinase/phosphorylated Akt/nuclear factor kappa B
      (PI3K/pAkt/NFkappaB)-signaling pathway, whereas cluster of differentiation 44
      (CD44) binding and mammalian target of rapamycin/70-kDa ribosomal protein S6
      kinase (mTOR/p70S6K) were not involved. Neutralization of integrin alpha(v)
      beta(3) prevented the OPN-mediated activation of the PI3K/pAkt/NFkappaB-signaling
      cascade and Collagen-I up-regulation. Likewise, inhibition of PI3K and NFkappaB
      blocked the OPN-mediated Collagen-I increase. Hepatitis C Virus (HCV) cirrhotic
      patients showed coinduction of Collagen-I and cleaved OPN compared to healthy
      individuals. Acute and chronic liver injury by CCl(4) injection or thioacetamide
      (TAA) treatment elevated OPN expression. Reactive oxygen species up-regulated OPN
      in vitro and in vivo and antioxidants prevented this effect. Transgenic mice
      overexpressing OPN in hepatocytes (Opn(HEP) Tg) mice developed spontaneous liver
      fibrosis compared to WT mice. Last, chronic CCl(4) injection and TAA treatment
      caused more liver fibrosis to WT than to Opn(-/-) mice and the reverse occurred
      in Opn(HEP) Tg mice. CONCLUSION: OPN emerges as a key cytokine within the ECM
      protein network driving the increase in Collagen-I protein contributing to
      scarring and liver fibrosis.

PMID- 21953218
TI  - Changes in the electrical and contractile activities of rat atrial myocardium
      caused by carbon monoxide.

PMID- 21953219
TI  - Frequency threshold curves of auditory interneurons of male mosquitoes Culex
      pipiens pipiens L. (Diptera, Culicidae).

PMID- 21953220
TI  - Simulation of the interferon-mediated protective field in lymphoid organs with
      their spatial and functional organization taken into consideration.

PMID- 21953221
TI  - Genomic study of gene expression in the mouse lumbar spinal cord under the
      conditions of simulated microgravity.

PMID- 21953222
TI  - The effect of emotional stress on the expression of the alpha-ENaC gene mRNA in
      the kidney of hypertensive ISIAH rats.

PMID- 21953223
TI  - Functional geometry of human left ventriculum in ontogenesis.

PMID- 21953224
TI  - Semax increases erythrocyte deformability in the shearing blood stream in intact
      rats and rats with cerebral ischemia.

PMID- 21953225
TI  - Photoactivation and chemical activation of single electron transfer in pathology
      modeling on DBA/2 mice.

PMID- 21953226
TI  - Taxonomic value of petiole anatomy in the genus Megadenia Maxim. (Cruciferae).

PMID- 21953227
TI  - Continuous biomonitoring of behavioral responses of mussels: the first experience
      in the Kola Bay (Barents Sea).

PMID- 21953228
TI  - The effect of amplitude modulation on the spectrum structure of the Pallas's Pika
      (Mammalia, Lagomorpha) sound signal.

PMID- 21953229
TI  - Interpopulation karyotype variability in hamster of the "barabensis" Group
      (Cricetidae, Rodentia) from Central Mongolia and possible reasons of its origin.

PMID- 21953230
TI  - Carotenoids of phototrophic organisms in bottom sediments of meromictic Lake
      Shira (Siberia, Russia) as an indicator of past stratification.

PMID- 21953231
TI  - Comparison of the resistances of Arabidopsis (Arabidopsis thaliana) and
      Thellungiella (Thellungiella salsuginea) suspension cultures to high
      temperatures.

PMID- 21953232
TI  - NO-dependent accumulation of inorganic ions and proline determines the protective
      effect of nitric oxide on mustard growth under the conditions of salinization.

PMID- 21953233
TI  - Kinematics of the shoulder girdle in bats.

PMID- 21953234
TI  - Bighorn sheep from Yakutia.

PMID- 21953235
TI  - Accumulation of 241Am by crucian carp from food and water.

PMID- 21953236
TI  - Peculiarities of megabenthos distribution in the upper sublittoral zone of Kola
      Bay (the Barents Sea).

PMID- 21953237
TI  - Characteristics of seasonal dynamics of Betula platyphylla Sukacz. Dehydrins
      associated with frost hardiness development under the cryolitic zone conditions.

PMID- 21953238
TI  - Are melibiose-fermenting intestinal and alpechin strains of Saccharomyces
      cerevisiae a novel type of yeast probiotics?

PMID- 21953239
TI  - The influence of silatranes, germatranes, protatranes, and triethanolamine on
      vital functions of microorganisms.

PMID- 21953240
TI  - Sonographic diagnosis of choledochocele.
AB  - We present a case of a 48-year-old female with a history of cholecystectomy and
      recurrent attacks of pancreatitis whose initial abdominal sonography (US)
      revealed multiple conglomerated stones in the descending part of the duodenum.
      Abdominal CT, MRI, and magnetic resonance cholangiopancreatography showed the
      same findings. The distended sacciform distal intramural segment of the common
      bile duct was protruding into the duodenum. The imaging findings explained the
      etiology of the patient's recurrent attacks of pancreatitis and led to surgical
      excision of the choledococele.

PMID- 21953241
TI  - Decreased insulin sensitivity and increased oxidative damage in wasting adipose
      tissue depots of wild-type mice.
AB  - Unintentional weight loss (wasting) in the elderly is a major health concern as
      it leads to increased mortality. Several studies have focused on muscle loss, but
      little is known about the mechanisms giving rise to loss of fat mass at old ages.
      To investigate potential mechanisms, white adipose tissue (WAT) characteristics
      and proteomic profiles were compared between adult (10-12-month-old) and aged (22
      24-month-old) wild-type mice. Four individual WAT depots were analyzed to account
      for possible depot-specific differences. Proteomic profiles of WAT depots, along
      with body weights and compositions, plasma levels of insulin, leptin and
      adiponectin, insulin tolerance, adipocyte sizes, and products of oxidative damage
      in each WAT depot were determined. We found that lean mass remained constant
      while fat mass and insulin tolerance were decreased in old age, as were adipocyte
      sizes in the WAT depots. Proteomic results showed increased levels of enolase,
      pyruvate dehydrogenase E1beta, NAD(+)-dependent isocitrate dehydrogenase alpha,
      and ATP synthase subunit beta, and decreased levels of carbonic anhydrase 3 in
      WAT of aged mice. These data suggest increased aerobic glucose oxidation in
      wasting WAT, consistent with decreased insulin signaling. Also, Cu/Zn superoxide
      dismutase and two chaperones were increased in aged WAT depots, indicating higher
      stress resistance. In agreement, lipid peroxidation (HNE-His adducts) increased
      in old age, although protein oxidation (carbonyl groups) showed no increase. In
      conclusion, features of wasting WAT were similar in the four depots, including
      decreased adipocyte sizes and alterations in protein expression profiles that
      indicated decreased insulin sensitivity and increased lipid peroxidation.

PMID- 21953242
TI  - The effects of the intraperitoneal administration of oxaliplatin and 5-FU on the
      healing of colonic anastomoses: an experimental study.
AB  - BACKGROUND: The purpose of this experimental study was to assess the effects of
      the immediate postoperative intraperitoneal administration of oxaliplatin and 5
      FU on the healing of colonic anastomoses in rats. METHODS: Sixty rats were
      randomized into 4 groups of 15 rats each and were subjected to colonic
      anastomoses. To the 1st group, saline solution was administered immediately
      postoperatively, intraperitoneally. To the 2nd group, 5-FU was administered, to
      the 3rd group oxaliplatin and to the 4th group 5-FU and oxaliplatin were
      administered immediately postoperatively, intraperitoneally. After killing the
      rats on the 8th postoperative day, the anastomoses were examined macroscopically
      and the anastomotic bursting pressures were measured. The anastomoses were also
      examined histologically and the hydroxyproline contents were determined. RESULTS:
      Rupture of the anastomosis was observed in no rats of the 1st group, in 3 rats of
      the 2nd group, in 4 rats of the 3rd group and in 7 rats of the 4th group (P =
      0.016). The bursting pressure (P < 0.001), the hydroxyproline content (P < 0.001)
      and the concentration of collagen (P < 0.001) and fibroblasts (P < 0.001) were
      significantly lower in the 2nd, 3rd and 4th group in comparison with the 1st
      group. The formation of adhesions and the leukocytosis on the anastomoses were
      significantly higher in the 2nd, 3rd and 4th group than in the 1st group (P <
      0.001). CONCLUSIONS: The immediate postoperative, intraperitoneal administration
      of oxaliplatin, 5-FU or the combination of 5-FU and oxaliplatin impairs the
      healing of colonic anastomoses in rats.

PMID- 21953243
TI  - Robotic TransAnal Minimally Invasive Surgery in a cadaveric model.
AB  - The technique of TransAnal Minimally Invasive Surgery (TAMIS) was pioneered in
      2009 as a hybrid approach to endoluminal resections of appropriately selected
      rectal lesions. There are, however, limitations to performing this type of
      resection. Robotic TAMIS is a novel, experimental technique and in this study was
      performed in a cadaveric model at a surgical education center. Various tasks were
      carried out using robotic TAMIS, including full-thickness sharp and cautery
      excision of rectal wall, as well as intra-luminal suturing of the surgical
      defect. It was found that for the da Vinci-trained surgeon, these tasks were
      simple to perform and accomplished with greater precision when compared to
      standard TAMIS. Our initial results indicate that robotic TAMIS overcomes the
      limitations of standard TAMIS and that it is a feasible platform for transanal
      surgery. The cost, however, of performing robotic TAMIS may limit its application
      to special cases in which standard TAMIS or transanal endoscopic microsurgery
      resections may prove difficult. Further study is necessary to validate these
      preliminary findings before robotic TAMIS is performed on live patients.

PMID- 21953245
TI  - Impact of sodium chloride on wheat flour dough for yeast-leavened products. I.
      Rheological attributes.
AB  - BACKGROUND: The rheological properties of wheat dough for yeast-leavened products
      were tested at different levels of sodium chloride (NaCl) addition ranging from 0
      to 40 g NaCl kg-1 wheat flour. Rheological tests carried out to make this
      evaluation included (1) empirical rheological methods of the Farinograph, load
      extension and a dough stickiness test and (2) fundamental rheological methods of
      creep recovery and dynamic rheometry. Modifications to the gluten matrix
      microstructure by NaCl were examined by confocal laser-scanning microscopy.
      RESULTS: Highly significant (P?0.001) differences due to NaCl addition could be
      determined in particular by the stickiness test as well as by examination of the
      creep test with the Burger model. Rheological changes measured in the creep test
      probably depend on protein charge shielding due to NaCl interaction, resulting in
      an improvement in gluten network formation. An increase in dough stickiness was
      measured when using NaCl. CONCLUSION: The present result for stickiness is
      contrary to the common subjective results. Therefore the theory proposed here for
      increased stickiness suggests that it is based on more non-protein-bound water in
      the dough system due to NaCl interaction and thus more viscous dough behaviour,
      which leads to higher stickiness as measured with the stickiness test. This may
      also suggest that the objectively measured 'stickiness' in this case does not
      properly indicate the subjectively measured stickiness it was designed to
      represent.

PMID- 21953246
TI  - Differential magnetic field effects on heart rate and nociception in anosmic
      pigeons.
AB  - Several studies have shown that exposure to altered magnetic fields affects
      nociception by suppressing stress-induced hypoalgesia, and that this effect is
      reduced or abolished if the treatment is performed in the absence of light. This
      raises the question as to whether other sources of sensory stimuli may also
      modulate these magnetic effects. We investigated the possible role of olfaction
      in the magnetically induced effects on sensitivity to nociceptive stimuli and
      heart rate (HR) in restraint-stressed homing pigeons exposed to an Earth
      strength, irregularly varying (<1 Hz) magnetic field. The magnetic treatment
      decreased the nociceptive threshold in normally smelling birds and an opposite
      effect was observed in birds made anosmic by nostril plugging. Conversely, no
      differential effect of olfactory deprivation was observed on HR, which was
      reduced by the magnetic treatment both in smelling and anosmic pigeons. The
      findings highlight an important role of olfactory environmental information in
      the mediation of magnetic effects on nociception, although the data cannot be
      interpreted unambiguously because of the lack of an additional control group of
      olfactory-deprived, non-magnetically exposed pigeons. The differential effects on
      a pigeon's sensitivity to nociceptive stimulus and HR additionally indicate that
      the magnetic stimuli affect nociception and the cardiovascular system in
      different ways.

PMID- 21953247
TI  - Glycosaminoglycan mimicry by COAM reduces melanoma growth through chemokine
      induction and function.
AB  - Chlorite-oxidized oxyamylose (COAM), a glycosaminoglycan mimetic and potent
      antiviral agent, provided significant growth reduction of syngeneic murine B16-F1
      melanoma tumors. A single early dose (100 MUg, into the site of tumor cell
      inoculation) was sufficient to establish a persistent effect over 17 days
      (resected tumor volume of 78.3 mm(3)  in COAM-treated mice compared to 755.2
      mm(3)  in the control cohort, i.e., 89.6% reduction of tumor volumes). COAM was a
      much better antitumoral agent than the polyanionic glycosaminoglycan heparin.
      COAM retained its antitumoral effect in lymphopenic mice, reinforcing the idea of
      myeloid cell involvement. Massive recruitment of myeloid cells into dermal air
      pouches in response to COAM and their increased presence in early-treated tumors
      indicated that mainly CD11b(+)  GR-1(+)  myeloid cells were attracted by COAM to
      exert antitumoral effects. Leukocyte chemotaxis was mediated by the chemokine
      system through the induction in B16-F1 cells of mouse granulocyte chemotactic
      protein-2/CXCL6 upon COAM treatment. Thus, COAM constitutes a novel tool to study
      the role of innate immune cells in the initial stages of tumor development and an
      example that innate immunostimulating glycosaminoglycan mimicry may be exploited
      therapeutically.

PMID- 21953248
TI  - Phase 2 study of bevacizumab plus erlotinib in patients with advanced
      hepatocellular cancer.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) and vascular endothelial
      growth factor (VEGF) are rational targets for therapy in hepatocellular cancer
      (HCC). METHODS: Patients with histologically proven HCC and not amenable to
      curative or liver directed therapy were included in this 2-stage phase 2 trial.
      Eligibility included an Eastern Cooperative Oncology Group (ECOG) performance
      status (PS) of 0 or 1 and Child's Pugh score of A or B, and 1 prior systemic
      therapy. Patients received erlotinib 150 mg daily and bevacizumab 10 mg/kg on
      days 1 and 15 every 28 days. Objective tumor response was the primary end point.
      RESULTS: Twenty-seven patients with advanced HCC (median age, 60 years) were
      enrolled in this multi-institutional study. The proportion of patients with
      Child's A classification was 74%. One patient had a confirmed partial response
      and 11 (48%) achieved stable disease. Median time to disease progression was 3.0
      months (95% confidence interval [CI], 1.8-7.1). Median survival time was 9.5
      months (95% CI, 7.1-17.1). Grade 3 toxicities included rash, hypertension,
      fatigue, and diarrhea. CONCLUSIONS: In this trial, erlotinib combined with
      bevacizumab had minimal activity in patients with advanced HCC based on objective
      response and progression-free survival. The role of targeting EGFR and VEGF in
      HCC needs further evaluation in molecularly selected patients.

PMID- 21953249
TI  - CERT depletion predicts chemotherapy benefit and mediates cytotoxic and polyploid
      specific cancer cell death through autophagy induction.
AB  - Chromosomal instability (CIN) has been implicated in multidrug resistance and the
      silencing of the ceramide transporter, CERT, promotes sensitization to diverse
      cytotoxics. An improved understanding of mechanisms governing multidrug
      sensitization might provide insight into pathways contributing to the death of
      CIN cancer cells. Using an integrative functional genomics approach, we find that
      CERT-specific multidrug sensitization is associated with enhanced autophagosome
      lysosome flux, resulting from the expression of LAMP2 following CERT silencing in
      colorectal and HER2(+) breast cancer cell lines. Live cell microscopy analysis
      revealed that CERT depletion induces LAMP2-dependent death of polyploid cells
      following exit from mitosis in the presence of paclitaxel. We find that CERT is
      relatively over-expressed in HER2(+) breast cancer and CERT protein expression
      acts as an independent prognostic variable and predictor of outcome in adjuvant
      chemotherapy-treated patients with primary breast cancer. These data suggest that
      the induction of LAMP2-dependent autophagic flux through CERT targeting may
      provide a rational approach to enhance multidrug sensitization and potentiate the
      death of polyploid cells following paclitaxel exposure to limit the acquisition
      of CIN and intra-tumour heterogeneity.

PMID- 21953250
TI  - An ion mobility/ion trap/photodissociation instrument for characterization of ion
      structure.
AB  - A new instrument that combines ion mobility spectrometry (IMS) separations with
      tandem mass spectrometry (MS(n)) is described. Ion fragmentation is achieved with
      vacuum ultraviolet photodissociation (VUV PD) and/or collision-induced
      dissociation (CID). The instrument is comprised of an approximately 1 m long
      drift tube connected to a linear trap that has been interfaced to a pulsed F(2)
      laser (157 nm). Ion gates positioned in the front and the back of the primary
      drift region allow for mobility selection of specific ions prior to their storage
      in the ion trap, mass analysis, and fragmentation. The ion characterization
      advantages of the new instrument are demonstrated with the analysis of the
      isomeric trisaccharides, melezitose and raffinose. Mobility separation of
      precursor ions provides a means of separating the isomers and subsequent VUV PD
      generates unique fragments allowing them to be distinguished.

PMID- 21953251
TI  - Adaptation of a 3-D quadrupole ion trap for dipolar DC collisional activation.
AB  - Means to allow for the application of a dipolar DC pulse to the end-cap
      electrodes of a three-dimensional (3-D) quadrupole ion trap for as short as a
      millisecond to as long as hundreds of milliseconds are described. The
      implementation of dipolar DC does not compromise the ability to apply AC
      waveforms to the end-cap electrodes at other times in the experiment. Dipolar DC
      provides a nonresonant means for ion acceleration by displacing ions from the
      center of the ion trap where they experience stronger rf electric fields, which
      increases the extent of micro-motion. The evolution of the product ion spectrum
      to higher generation products with time, as shown using protonated leucine
      enkephalin as a model protonated peptide, illustrates the broad-band nature of
      the activation. Dipolar DC activation is also shown to be effective as an ion
      heating approach in mimicking high amplitude short time excitation (HASTE)/pulsed
      Q dissociation (PQD) resonance excitation experiments that are intended to
      enhance the likelihood for observing low m/z products in ion trap tandem mass
      spectrometry.

PMID- 21953252
TI  - Sequential and exhaustive ionization of analytes with different surface activity
      by probe electrospray ionization.
AB  - The probe electrospray ionization (PESI) is an ESI-based ionization technique
      that generates electrospray from the tip of a solid metal needle. In this work,
      mass spectra for the single-shot PESI were measured as a function of time for a
      mixture of several analytes with different surface activity values. It was found
      that the analytes were elecrosprayed in the order of their surface activity. For
      example, detergent and protein were detected separately and respectively at the
      first and last stages of electrospray, for a mixed sample of 10(-3) M Triton X100
      and 10(-5) M cytochrome c. For human breast cancer tissue, at first proteins such
      as alpha and beta chains of hemoglobin, were observed as the dominant ions, but
      just before the liquid droplet on the needle was depleted only lipids were
      observed, meaning that PESI has the advantage of the suppression effect with
      analytes being detected separately in the order of their surface activity values.

PMID- 21953253
TI  - Quantitative analysis of therapeutic drugs in dried blood spot samples by paper
      spray mass spectrometry: an avenue to therapeutic drug monitoring.
AB  - A method is presented for the direct quantitative analysis of therapeutic drugs
      from dried blood spot samples by mass spectrometry. The method, paper spray mass
      spectrometry, generates gas phase ions directly from the blood card paper used to
      store dried blood samples without the need for complex sample preparation and
      separation; the entire time for preparation and analysis of blood samples is
      around 30 s. Limits of detection were investigated for a chemically diverse set
      of some 15 therapeutic drugs; hydrophobic and weakly basic drugs, such as
      sunitinib, citalopram, and verapamil, were found to be routinely detectable at
      approximately 1 ng/mL. Samples were prepared by addition of the drug to whole
      blood. Drug concentrations were measured quantitatively over several orders of
      magnitude, with accuracies within 10% of the expected value and relative standard
      deviation (RSD) of around 10% by prespotting an internal standard solution onto
      the paper prior to application of the blood sample. We have demonstrated that
      paper spray mass spectrometry can be used to quantitatively measure drug
      concentrations over the entire therapeutic range for a wide variety of drugs. The
      high quality analytical data obtained indicate that the technique may be a viable
      option for therapeutic drug monitoring.

PMID- 21953254
TI  - Cage structure formation of singly doped aluminum cluster cations Al(n)TM+ (TM =
      Ti, V, Cr).
AB  - Structural information on free transition metal doped aluminum clusters,
      Al(n)TM(+) (TM = Ti, V, Cr), was obtained by studying their ability for argon
      physisorption. Systematic size (n = 5-35) and temperature (T = 145-300 K)
      dependent investigations reveal that bare Al(n)(+) clusters are inert toward
      argon, while Al(n)TM(+) clusters attach one argon atom up to a critical cluster
      size. This size is interpreted as the geometrical transition from surface-located
      dopant atoms to endohedrally doped aluminum clusters with the transition metal
      atom residing in an aluminum cage. The critical size, n(crit), is found to be
      surprisingly large, namely n(crit) = 16 and n(crit) = 19-21 for TM = V, Cr, and
      TM = Ti, respectively. Experimental cluster-argon bond dissociation energies have
      been derived as function of cluster size from equilibrium mass spectra and are in
      the 0.1-0.3 eV range.

PMID- 21953255
TI  - "Meta elimination," a diagnostic fragmentation in mass spectrometry.
AB  - The diagnostic value of the "ortho effect" for unknown identification by mass
      spectrometry is well known. Here, we report the existence of a novel "meta
      effect," which adds to the repertoire of useful mass spectrometric fragmentation
      mechanisms. For example, the meta-specific elimination pathway described in this
      report enables unequivocal identification of meta isomers from ortho and para
      isomers of carboxyanilides. The reaction follows a specific path to eliminate a
      molecule of meta-benzyne, from the anion produced after the initial
      decarboxylation of the precursor. Consequently, in the CID spectra of
      carboxyanilides, a peak for the (R-CO-NH)(-) anion is observed only for the meta
      isomers. For example, the peaks observed at m/z 58, 86, 120, 128, and 170 from
      acetamido-, butamido-, benzamido, heptamido-, and decanamido-benzoates,
      respectively, were specific only to the spectra of meta isomers.

PMID- 21953256
TI  - N-centered odd-electron ions formation from collision-induced dissociation of
      electrospray ionization generated even-electron ions: single electron transfer
      via ion/neutral complex in the fragmentation of protonated N,N'
      dibenzylpiperazines and protonated N-benzylpiperazines.
AB  - Single electron transfer (SET) via ion/neutral complex (INC) was proposed and
      confirmed to be the key step in the formation of N-centered odd-electron ions
      from fragmentation of protonated even-electron ions in the present study. Upon
      collisional activation, the model compounds, protonated N,N'-dibenzylpiperazine
      and protonated N-benzylpiperazines initially dissociated to form intermediate
      INCs consisting of N-benzylpiperazine (or piperazine) and benzyl cation. In these
      ion/neutral complexes, SET reaction and direct separation as well as other
      reactions were observed and characterized experimentally and theoretically.
      Density functional theory calculations demonstrated that the energy requirement
      for homolysis of the precursor ion was so large that it could not be achieved,
      whereas the heterolytic dissociation followed by electron transfer via INC was
      energetically preferred. The SET process occurred only when the radical products
      were more stable than the separation products. The energy barrier for SET in the
      compounds studied was roughly estimated by comparison with other competing
      reactions. When the INC contained electron donor with lower ionization energy and
      electron acceptor with higher electron affinity, the SET reaction was more
      efficient.

PMID- 21953257
TI  - Gas-phase fragmentation analysis of nitro-fatty acids.
AB  - Nitro-fatty acids are electrophilic signaling mediators formed in increased
      amounts during inflammation by nitric oxide and nitrite-dependent redox
      reactions. A more rigorous characterization of endogenously-generated species
      requires additional understanding of their gas-phase induced fragmentation. Thus,
      collision induced dissociation (CID) of nitroalkane and nitroalkene groups in
      fatty acids were studied in the negative ion mode to provide mass spectrometric
      tools for their structural characterization. Fragmentation of nitroalkanes
      occurred mainly through loss of the NO(2)(-) anion or neutral loss of HNO(2). The
      CID of nitroalkenes proceeds via a more complex cyclization, followed by
      fragmentation to nitrile and aldehyde products. Gas-phase fragmentation of
      nitroalkene functional groups with additional gamma or delta unsaturation
      occurred through a multiple step cyclization reaction process, leading to 5 and 6
      member ring heterocyclic products and carbon chain fragmentation. Cyclization
      products were not obtained during nitroalkane fragmentation, highlighting the
      role of double bond pi electrons during NO(2)(-) rearrangements, stabilization
      and heterocycle formation. The proposed structures, mechanisms and products of
      fragmentation are supported by analysis of (13)C and (15)N labeled parent
      molecules, 6 different nitroalkene positional isomers, 6 nitroalkane positional
      isomers, accurate mass determinations at high resolution and quantum mechanics
      calculations. Multiple key diagnostic ion fragments were obtained through this
      analysis, allowing for the precise placement of double bonds and sites of fatty
      acid nitration, thus supporting an ability to predict nitro positions in
      biological samples.

PMID- 21953258
TI  - Localization of fatty acyl and double bond positions in phosphatidylcholines
      using a dual stage CID fragmentation coupled with ion mobility mass spectrometry.
AB  - A high content molecular fragmentation for the analysis of phosphatidylcholines
      (PC) was achieved utilizing a two-stage [trap (first generation fragmentation)
      and transfer (second generation fragmentation)] collision-induced dissociation
      (CID) in combination with travelling-wave ion mobility spectrometry (TWIMS). The
      novel aspects of this work reside in the fact that a TWIMS arrangement was used
      to obtain a high level structural information including location of fatty acyl
      substituents and double bonds for PCs in plasma, and the presence of alkali metal
      adduct ions such as [M + Li](+) was not required to obtain double bond positions.
      Elemental compositions for fragment ions were confirmed by accurate mass
      measurements. A very specific first generation fragment ion m/z 577 (M-phosphoryl
      choline) from the PC [16:0/18:1 (9Z)] was produced, which by further CID
      generated acylium ions containing either the fatty acyl 16:0 (C(15)H(31)CO(+),
      m/z 239) or 18:1 (9Z) (C(17)H(33)CO(+), m/z 265) substituent. Subsequent water
      loss from these acylium ions was key in producing hydrocarbon fragment ions
      mainly from the alpha-proximal position of the carbonyl group such as the
      hydrocarbon ion m/z 67 (+H(2)C-HC = CH-CH = CH(2)). Formation of these ions was
      of important significance for determining double bonds in the fatty acyl chains.
      In addition to this, and with the aid of (13)C labeled lyso-phosphatidylcholine
      (LPC) 18:1 (9Z) in the omega-position (methyl) TAP fragmentation produced the ion
      at m/z 57. And was proven to be derived from the alpha-proximal (carboxylate) or
      distant omega-position (methyl) in the LPC.

PMID- 21953260
TI  - Thermochemistry of microhydration of sodiated and potassiated monosaccharides.
AB  - The thermochemical properties DeltaH(o)(n), DeltaS(o)(n), and DeltaG(o)(n) for
      the hydration of sodiated and potassiated monosaccharides (Ara = arabinose, Xyl =
      xylose, Rib = ribose, Glc = glucose, and Gal = galactose) have been
      experimentally studied in the gas phase at 10 mbar by equilibria measurements
      using an electrospray high-pressure mass spectrometer equipped with a pulsed ion
      beam reaction chamber. The hydration enthalpies for sodiated complexes were found
      to be between -46.4 and -57.7 kJ/mol for the first, and -42.7 and -52.3 kJ/mol
      for the second water molecule. For potassiated complexes, the water binding
      enthalpies were similar for all studied systems and varied between -48.5 and 
      52.7 kJ/mol. The thermochemical values for each system correspond to a mixture of
      the alpha and beta anomeric forms of monosaccharide structures involved in their
      cationized complexes.

PMID- 21953261
TI  - LC-MS(n) analysis of isomeric chondroitin sulfate oligosaccharides using a
      chemical derivatization strategy.
AB  - Improved methods for structural analyses of glycosaminoglycans (GAGs) are
      required to understand their functional roles in various biological processes.
      Major challenges in structural characterization of complex GAG oligosaccharides
      using liquid chromatography-mass spectrometry (LC-MS) include the accurate
      determination of the patterns of sulfation due to gas-phase losses of the sulfate
      groups upon collisional activation and inefficient on-line separation of
      positional sulfation isomers prior to MS/MS analyses. Here, a sequential chemical
      derivatization procedure including permethylation, desulfation, and acetylation
      was demonstrated to enable both on-line LC separation of isomeric mixtures of
      chondroitin sulfate (CS) oligosaccharides and accurate determination of sites of
      sulfation by MS(n). The derivatized oligosaccharides have sulfate groups replaced
      with acetyl groups, which are sufficiently stable to survive MS(n) fragmentation
      and reflect the original sulfation patterns. A standard reversed-phase LC-MS
      system with a capillary C18 column was used for separation, and MS(n) experiments
      using collision-induced dissociation (CID) were performed. Our results indicate
      that the combination of this derivatization strategy and MS(n) methodology
      enables accurate identification of the sulfation isomers of CS hexasaccharides
      with either saturated or unsaturated nonreducing ends. Moreover, derivatized CS
      hexasaccharide isomer mixtures become separable by LC-MS method due to different
      positions of acetyl modifications.

PMID- 21953262
TI  - NanoESI mass spectrometry of Rubisco and Rubisco activase structures and their
      interactions with nucleotides and sugar phosphates.
AB  - Ribulose bisphosphate carboxylase/oxygenase (Rubisco) is the protein that is
      responsible for the fixation of carbon dioxide in photosynthesis. Inhibitory
      sugar phosphate molecules, which can include its substrate ribulose-1,5
      bisphosphate (RuBP), can bind to Rubisco catalytic sites and inhibit catalysis.
      These are removed by interaction with Rubisco activase (RA) via an ATP hydrolytic
      reaction. Here we show the first nanoESI mass spectra of the hexadecameric
      Rubisco and of RA from a higher plant (tobacco). The spectra of recombinant,
      purified RA revealed polydispersity in its oligomeric forms (up to hexamer) and
      that ADP was bound. ADP was removed by dialysis against a high ionic strength
      solution and nucleotide binding experiments showed that ADP bound more tightly to
      RA than AMP-PNP (a non-hydrolysable ATP analog). There was evidence that there
      may be two nucleotide binding sites per RA monomer. The oligomerization capacity
      of mutant and wild-type tobacco RA up to hexamers is analogous to the subunit
      stoichiometry for other AAA+ enzymes. This suggests assembly of RA into hexamers
      is likely the most active conformation for removing inhibitory sugar phosphate
      molecules from Rubisco to enable its catalytic competency. Stoichiometric binding
      of RuBP or carboxyarabinitol bisphosphate (CABP) to each of the eight catalytic
      sites of Rubisco was observed.

PMID- 21953263
TI  - Biologically-inspired peptide reagents for enhancing IMS-MS analysis of
      carbohydrates.
AB  - The binding properties of a peptidoglycan recognition protein are translated via
      combinatorial chemistry into short peptides. Non-adjacent histidine, tyrosine,
      and arginine residues in the protein's binding cleft that associate specifically
      with the glycan moiety of a peptidoglycan substrate are incorporated into linear
      sequences creating a library of 27 candidate tripeptide reagents (three possible
      residues permutated across three positions). Upon electrospraying the peptide
      library and carbohydrate mixtures, some noncovalent complexes are observed. The
      binding efficiencies of the peptides vary according to their amino acid
      composition as well as the disaccharide linkage and carbohydrate ring-type. In
      addition to providing a charge-carrier for the carbohydrate, peptide reagents can
      also be used to differentiate carbohydrate isomers by ion mobility spectrometry.
      The utility of these peptide reagents as a means of enhancing ion mobility
      analysis of carbohydrates is illustrated by examining four glucose-containing
      disaccharide isomers, including a pair that is not resolved by ion mobility
      alone. The specificity and stoichiometry of the peptide-carbohydrate complexes
      are also investigated. Trihistidine demonstrates both suitable binding efficiency
      and successful resolution of disaccharides isomers, suggesting it may be a useful
      reagent in IMS analyses of carbohydrates.

PMID- 21953264
TI  - Tandem MS analysis of selenamide-derivatized peptide ions.
AB  - Our previous study showed that selenamide reagents such as ebselen and N
      (phenylseleno)phthalimide (NPSP) can be used for selective and rapid
      derivatization of protein/peptide thiols in high conversion yield. This paper
      reports the systematic investigation of MS/MS dissociation behaviors of
      selenamide-derivatized peptide ions upon collision induced dissociation (CID) and
      electron transfer dissociation (ETD). In the positive ion mode, derivatized
      peptide ions exhibit tag-dependent CID dissociation pathways. For instance,
      ebselen-derivatized peptide ions preferentially undergo Se-S bond cleavage upon
      CID to produce a characteristic fragment ion, the protonated ebselen (m/z 276),
      which allows selective identification of thiol peptides from protein digest as
      well as selective detection of thiol proteins from protein mixture using
      precursor ion scan (PIS). In contrast, NPSP-derivatized peptide ions retain their
      phenylselenenyl tags during CID, which is useful in sequencing peptides and
      locating cysteine residues. In the negative ion CID mode, both types of tags are
      preferentially lost via the Se-S cleavage, analogous to the S-S bond cleavage
      during CID of disulfide-containing peptide anions. In consideration of the
      convenience in preparing selenamide-derivatized peptides and the similarity of Se
      S of the tag to the S-S bond, we also examined ETD of the derivatized peptide
      ions to probe the mechanism for electron-based ion dissociation. Interestingly,
      facile cleavage of Se-S bond occurs to the peptide ions carrying either protons
      or alkali metal ions, while backbone cleavage to form c/z ions is severely
      inhibited. These results are in agreement with the Utah-Washington mechanism
      proposed for depicting electron-based ion dissociation processes.

PMID- 21953265
TI  - Negative ion fragmentation of cysteic acid containing peptides: cysteic acid as a
      fixed negative charge.
AB  - We present here a study of the collision induced dissociation (CID) of
      deprotonated cysteic acid containing peptides produced by MALDI. The effect of
      cysteic acid (C(ox)) position is interrogated by considering the positional
      isomers, C(ox)LVINVLSQG, LVINVLSQGC(ox), and LVINVC(ox)LSQG. Although
      considerable variation between the CID spectra is observed, the mechanistic
      picture that emerges involves charge retention at the deprotonated cysteic acid
      side chain. Fragmentation occurs in the proximity of the cysteic acid group by
      charge directed mechanisms as well as remote from this group to form ions, which
      may be rationalized by charge remote mechanisms. Additionally, the formation of
      the SO(3)(-*) ion is observed in all cases. Fragmentation of C(ox)LVINVLSQC(ox)
      provides both N- and C-terminal, y and b ions, respectively indicating that the
      negative charge may be retained at either of the cysteic acids; however, there is
      some evidence that charge retention at the C-terminal cysteic acid may be
      preferred. Fragmentation of tryptic type peptides containing a C-terminal
      arginine or lysine residue is considered through comparison of three peptides
      C(ox)LVINKLSQG, C(ox)LVINVLSQK, and C(ox)LVINVLSQR. Lastly, we rationalize the
      formation of b(n-1)+ H(2)O and a(n-1) ions through a mechanism involving
      rearrangement of the C-terminal residue to form a mixed anhydride intermediate.

PMID- 21953266
TI  - Dissociation channel dependence on peptide size observed in electron capture
      dissociation of tryptic peptides.
AB  - Electron capture dissociation (ECD) of a series of five residue peptides led to
      the observation that these small peptides did not lead to the formation of the
      usual c/z ECD fragments, but to a, b, y, and w fragments. In order to determine
      how general this behavior is for small sized peptides, the effect of peptide size
      on ECD fragments using a complete set of ECD spectra from the SwedECD spectra
      database was examined. Analysis of the database shows that b and w fragments are
      favored for small peptide sizes and that average fragment size shows a linear
      relationship to parent peptide size for most fragment types. From these data, it
      appears that most of the w fragments are not secondary fragments of the major z
      ions, in sharp contrast with the proposed mechanism leading to these ions. These
      data also show that c fragment distributions depend strongly on the nature of C
      terminal residue basic site: arginine leads to loss of short neutral fragments,
      whereas lysine leads to loss of longer neutral fragments. It also appears that b
      ions might be produced by two different mechanisms depending on the parent
      peptide size. A model for the fragmentation pathways in competition is proposed.
      These relationships between average fragment size and parent peptide size could
      be further exploited also for CID fragment spectra and could be included in
      fragmentation prediction algorithms.

PMID- 21953267
TI  - Diagnosing the protonation site of b2 peptide fragment ions using IRMPD in the X
      H (X = O, N, and C) stretching region.
AB  - Charge-directed fragmentation has been shown to be the prevalent dissociation
      step for protonated peptides under the low-energy activation (eV) regime. Thus,
      the determination of the ion structure and, in particular, the characterization
      of the protonation site(s) of peptides and their fragments is a key approach to
      substantiate and refine peptide fragmentation mechanisms. Here we report on the
      characterization of the protonation site of oxazolone b(2) ions formed in
      collision-induced dissociation (CID) of the doubly protonated tryptic model
      peptide YIGSR. In support of earlier work, here we provide complementary IR
      spectra in the 2800-3800 cm(-1) range acquired on a table-top laser system.
      Combining this tunable laser with a high power CO(2) laser to improve
      spectroscopic sensitivity, well resolved bands are observed, with an excellent
      correspondence to the IR absorption bands of the ring-protonated oxazolone isomer
      as predicted by quantum chemical calculations. In particular, it is shown that a
      band at 3445 cm(-1), corresponding to the asymmetric N-H stretch of the
      (nonprotonated) N-terminal NH(2) group, is a distinct vibrational signature of
      the ring-protonated oxazolone structure.

PMID- 21953268
TI  - Experimental and theoretical investigation of the proton-bound dimer of lysine.
AB  - The structure of the proton-bound lysine dimer has been investigated by infrared
      multiple photon dissociation (IRMPD) spectroscopy and electronic structure
      calculations. The structures of different possible isomers of the proton-bound
      lysine dimer have been optimized at the B3LYP/6-31 + G(d) level of theory and IR
      spectra calculated using the same computational method. Based on relative Gibbs
      free energies (298 K) calculated at the MP2/aug-cc-pVTZ//B3LYP/6-31 + G(d) level
      of theory, LL-CS01, and followed closely (1.1 kJ mol(-1)) by LL-CS02 are the most
      stable non-zwitterionic isomers. At the MP2/aug-cc-pVTZ//6-31 + G(d) and MP2/aug
      cc-pVTZ//6-31 + (d,p) levels of theory, isomer LL-CS02 is favored by 3.0 and 2.3
      kJ mol(-1), respectively. The relative Gibbs free energies calculated by the
      aforementioned levels of theory for LL-CS01 and LL-CS02 are very close and
      strongly suggest that diagnostic vibrational signatures found in the IRMPD
      spectrum of the proton-bound dimer of lysine can be attributed to the existence
      of both isomers. LL-ZW01 is the most stable zwitterionic isomer, in which the
      zwitterionic structure of the neutral lysine is well stabilized by the protonated
      lysine moiety via a very strong intermolecular hydrogen bond. At the MP2/aug-cc
      pVTZ//B3LYP/6-31 + G(d), MP2/aug-cc-pVTZ//6-31 + G(d) and MP2/aug-cc-pVTZ//6-31 +
      G(d,p) levels of theory, the most stable zwitterionic isomer (LL-ZW01) is less
      favored than LL-CS01 by 7.3, 4.1 and 2.3 kJ mol(-1), respectively. The
      experimental IRMPD spectrum also confirms that the proton-bound dimer of lysine
      largely exists as charge-solvated isomers. Investigation of zwitterionic and
      charge-solvated species of amino acids in the gas phase will aid in a further
      understanding of structure, property, and function of biological molecules.

PMID- 21953269
TI  - Direct quantitative analysis of a 20 kDa PEGylated human calcitonin gene peptide
      antagonist in cynomolgus monkey serum using in-source CID and UPLC-MS/MS.
AB  - PEGylation is a successful strategy to improve the pharmacokinetic and
      pharmaceutical properties of therapeutic peptides. However, quantitative analysis
      of PEGylated peptides in biomatrix by LC-MS/MS poses significant analytical
      challenge due to the polydispersity of the polyethylene glycol (PEG), and the
      multiple charge states observed for both the peptide and PEG moieties. In this
      report, a novel LC-MS/MS method for direct quantitative analysis of 20 kDa
      PEGylated CGRP[Cit, Cit] in cynomolgus monkey serum is presented. CGRP[Cit, Cit]
      is an investigational human calcitonin gene peptide receptor antagonist with
      amino acid sequence Ac -WVTH[Cit]LAGLLS[Cit]SGGVVRKNFVPT DVGPFAF-NH(2). In-source
      collision-induced dissociation (in-source CID) of 20 kDa PEGylated peptide was
      used to generate CGRP[Cit, Cit] fragment ions, among which the most abundant
      b(8)(+) ion was selected and measured as a surrogate for the 20 kDa PEGylated
      peptide. A solid phase extraction (SPE) method was used to extract the PEGylated
      peptides from the biomatrix prior to the UPLC-MS/MS analysis. This method
      achieved a lower limit of quantitation (LLOQ) of 5.00 ng/mL with a serum sample
      volume of 100 MUL, and was linear over the calibration range of 5.00 to 500 ng/mL
      in cynomolgus monkey serum. Intraday and interday accuracy and precision from QC
      samples were within +/-15%. This method was successfully applied to a
      pharmacokinetic study of the 20 kDa PEGylated CGRP[Cit, Cit] in cynomolgus
      monkeys.

PMID- 21953270
TI  - Quantification of tryptic peptides in quadrupole ion trap using high-mass signals
      derived from isotope-coded N-acetyl dipeptide tags.
AB  - Isotope-labeled N-acetyl dipeptides (Ac-Xxx-Ala) are coupled to the primary
      amines of tryptic peptides and then analyzed by tandem mass spectrometry. Amide
      bond cleavage between Xxx and Ala provides both low- and high-mass isotope-coded
      signals for quantification of peptides. Especially, facile cleavage at the
      modified lysine side chain yields very strong high-mass quantitation signals in a
      noise-free region. Tagging tryptic peptides with isobaric N-acetyl dipeptides is
      a viable strategy for accurate quantification of proteins, which can be used with
      most quadrupole ion trap mass spectrometers carrying the 1/3 mass cut-off
      problem.

PMID- 21953271
TI  - In vitro cytotoxic screening of selected Saudi medicinal plants.
AB  - Many natural products from plants have been identified to exert anticancer
      activity. It might be expected to be a challenge to look at the Saudi plants in
      order to discover new sources for new molecules which may have anticancer
      activity. The methanolic extracts of forty species of plants traditionally used
      in Saudi Arabia for the treatment of a variety of diseases were tested in vitro
      for their potential anticancer activity on different human cancer cell lines. The
      cytotoxic activity of the methanolic extracts of the tested plants were
      determined using three human cancer cell lines, namely, breast cancer (MCF7),
      hepatocellular carcinoma (HEPG2), and cervix cancer (HELA) cells. In addition,
      human normal melanocyte (HFB4) was used as normal nonmalignant cells.
      Sulforhodamine B colorimetric assay was used to evaluate the in vitro cytotoxic
      activity of the different extracts. The growth inhibition of 50% (IC(50)) for
      each extract was calculated from the optical density of treated and untreated
      cells. Doxorubicin, a broad-spectrum anticancer drug, was used as the positive
      control. Nine plant extracts were chosen for further fractionation based on their
      activity and availability. Interesting cytotoxic activity was observed for
      Hypoestes forskaolii, Withania somnifera, Solanum glabratum, Adenium obesum,
      Pistacia vera oleoresin, Caralluma quadrangula, Eulophia petersii, Phragmanthera
      austroarabica, and Asparagus officinalis. Other extracts showed poor activity.

PMID- 21953272
TI  - Report of the Fifth meeting of the International Network for Pediatric
      Hemophilia: a focus on prophylaxis and immune tolerance induction.

PMID- 21953273
TI  - Molecular mechanisms of HTLV-1 infection and pathogenesis.
AB  - Human T cell leukemia virus type 1 (HTLV-1) is an etiological pathogen of several
      human diseases, including adult T-cell leukemia (ATL), HTLV-1-associated
      myelopathy (HAM)/tropical spastic paraparesis (TSP), and inflammatory disorders
      such as uveitis and dermatitis. HTLV-1 spreads mainly through cell-to-cell
      transmission, induces clonal proliferation of infected T cells in vivo, and after
      a long latent period, a subset of HTLV-1 carriers develop ATL. Understanding the
      molecular mechanisms of infection and oncogenesis is important for the
      development of new strategies of prophylaxis and molecular-targeted therapies,
      since ATL has a poor prognosis, despite intensive chemotherapy. In this review,
      we will summarize recent progress in HTLV-1 research, and especially novel
      findings on viral transmission and leukemogenic mechanisms by two viral
      oncogenes, HBZ and tax.

PMID- 21953274
TI  - Work productivity and health of informal caregivers of persons with advanced
      cancer.
AB  - The purpose of this study was to describe health promotion behaviors and work
      productivity loss in informal caregivers of individuals with advanced stage
      cancer. Using a cross-sectional, correlational design, 70 caregivers completed
      measures of health behaviors, mood, social support, and burden. Absenteeism and
      presenteeism were evaluated in employed caregivers (n = 40). Caregivers reported
      low levels of physical activity. The mean percentage of work productivity loss
      due to caregiving was 22.9%. Greater work productivity loss was associated with
      greater number of caregiving hours, higher cancer stage, married status, and
      greater anxiety, depression, and burden related to financial problems, disrupted
      schedule, and health. Nurses should assess caregivers and provide health
      promotion interventions, which may ultimately reduce the economic impact of
      caregiving.

PMID- 21953275
TI  - A phase I, open-label, randomized crossover study to assess the effect of dosing
      of the MEK 1/2 inhibitor Selumetinib (AZD6244; ARRY-142866) in the presence and
      absence of food in patients with advanced solid tumors.
AB  - PURPOSE: This Phase I study assessed whether food influences the rate and extent
      of selumetinib absorption in patients with advanced solid malignancies and
      determined the safety, tolerability, and pharmacokinetic (PK) profile of
      selumetinib and its active metabolite N-desmethyl-selumetinib in fed and fasted
      states. METHODS: A single dose of 75 mg selumetinib was to be taken with food on
      Day 1 followed by a single dose of 75 mg after fasting for at least 10 h on Day
      8, or vice versa, followed by twice daily dosing of 75 mg selumetinib from Day
      10. Plasma concentrations and PK parameters were determined on Days 1 and 8.
      Patients could continue to receive selumetinib for as long as they benefitted
      from treatment. RESULTS: In total, 31 patients were randomized to receive
      selumetinib; 15 to fed/fasted sequence and 16 to fasted/fed sequence.
      Comprehensive PK sampling was performed on 11 and 10 patients, respectively. The
      geometric least-squares means of C(max) and AUC for selumetinib were reduced by
      62% (ratio 0.38 90% CI 0.29, 0.50) and 19% (ratio 0.81 90% CI 0.74, 0.88),
      respectively, under fed compared with fasting conditions. The rate of absorption
      (t(max)) of selumetinib (fed) was delayed by approximately 2.5 h (median). The
      food effect was also observed for the active metabolite N-desmethyl-selumetinib.
      Selumetinib was well tolerated. CONCLUSIONS: The presence of food decreased the
      extent of absorption of selumetinib. It is recommended that for further clinical
      studies, selumetinib be taken on an empty stomach. Selumetinib demonstrated an
      acceptable safety profile in the advanced cancer population.

PMID- 21953277
TI  - Association studies of novel obesity-related gene variants with quantitative
      metabolic phenotypes in a population-based sample of 6,039 Danish individuals.
AB  - AIMS/HYPOTHESIS: Genome-wide association studies have identified novel WHR and
      BMI susceptibility loci. The aim of this study was to elucidate if any of these
      loci had an effect on quantitative measures of glucose homeostasis, including
      estimates of insulin release and insulin sensitivity in an epidemiological
      setting. METHODS: By applying an additive genetic model, 14 WHR-associated gene
      variants and 18 BMI-associated variants were investigated for their relationships
      with glucose-related metabolic traits in treatment-naive individuals from the
      population-based Inter99 study sample (n = 6,039). RESULTS: Of the variants
      associated with BMI, the QPCTL rs2287019 C allele was associated with an
      increased insulinogenic index of 7.4% per risk allele (p = 4.0 * 10-7) and
      increased disposition index of 5.6% (p = 6.4 * 10-5). The LRP1B rs2890652 C
      allele was associated with insulin resistance, showing a 3.3% increase (p =
      0.0011) using the HOMA-insulin resistance (HOMA-IR) index and a 2.2% reduction (p
      = 0.0014) with the Matsuda index. Of the variants associated with WHR,
      LYPLAL1/SLC30A10 rs4846567 G allele carriers showed a 5.2% lower HOMA-IR (p =
      0.00086) in women, indicating improved insulin sensitivity. Female carriers of
      the VEGFA rs6905288 A allele were insulin resistant, with a 3.7% increase in HOMA
      IR (p = 0.00036) and 4.0% decrease in Matsuda index (p = 2 * 10-4). CONCLUSIONS:
      Our correlative findings from analysing single-locus data suggest that some
      variation in validated BMI and WHR loci are associated with either increased or
      decreased insulin sensitivity and thereby potentially with metabolically healthy
      or metabolically unhealthy subsets of obesity. The results call for testing in
      larger study samples and for further physiological exploration of the possible
      metabolic implications of these loci.

PMID- 21953276
TI  - Diabetes mellitus, glycated haemoglobin and C-peptide levels in relation to
      pancreatic cancer risk: a study within the European Prospective Investigation
      into Cancer and Nutrition (EPIC) cohort.
AB  - AIMS/HYPOTHESIS: There has been long-standing debate about whether diabetes is a
      causal risk factor for pancreatic cancer or a consequence of tumour development.
      Prospective epidemiological studies have shown variable relationships between
      pancreatic cancer risk and blood markers of glucose and insulin metabolism,
      overall and as a function of lag times between marker measurements (blood
      donation) and date of tumour diagnosis. METHODS: Pre-diagnostic levels of HbA(1c)
      and C-peptide were measured for 466 participants with pancreatic cancer and 466
      individually matched controls within the European Prospective Investigation into
      Cancer and Nutrition. Conditional logistic regression models were used to
      estimate ORs for pancreatic cancer. RESULTS: Pancreatic cancer risk gradually
      increased with increasing pre-diagnostic HbA(1c) levels up to an OR of 2.42 (95%
      CI 1.33, 4.39 highest [>= 6.5%, 48 mmol/mol] vs lowest [<= 5.4%, 36 mmol/mol]
      category), even for individuals with HbA(1c) levels within the non-diabetic
      range. C-peptide levels showed no significant relationship with pancreatic cancer
      risk, irrespective of fasting status. Analyses showed no clear trends towards
      increasing hyperglycaemia (as marked by HbA(1c) levels) or reduced pancreatic
      beta cell responsiveness (as marked by C-peptide levels) with decreasing time
      intervals from blood donation to cancer diagnosis. CONCLUSIONS/INTERPRETATION:
      Our data on HbA(1c) show that individuals who develop exocrine pancreatic cancer
      tend to have moderate increases in HbA(1c) levels, relatively independently of
      obesity and insulin resistance-the classic and major risk factors for type 2
      diabetes. While there is no strong difference by lag time, more data are needed
      on this in order to reach a firm conclusion.

PMID- 21953279
TI  - Risk factors for relapse of antineutrophil cytoplasmic antibody-associated
      vasculitis.
AB  - OBJECTIVE: To determine the association between characteristics at diagnosis and
      the time to first relapse in a large cohort of patients with antineutrophil
      cytoplasmic antibody-associated vasculitis (AAV). METHODS: We studied long-term
      followup data from 4 clinical trials that included newly diagnosed patients with
      a broad spectrum of AAV severity and manifestations. Patient and disease
      characteristics at baseline were used in competing risk regression models with
      relapse as the event of interest and death as the competing event. RESULTS: We
      assessed 535 patients with 1,804 patient-years at risk of relapse. At diagnosis,
      the median age was 60.7 years (interquartile range [IQR] 48.8-69.1 years), 284
      patients (53%) had granulomatosis with polyangiitis (Wegener's), and the median
      creatinine level was 203 MUmoles/liter (IQR 97-498). A total of 201 patients
      (38%) experienced a relapse and 133 patients (25%) died, 96 of whom had not had
      prior relapse. Anti-proteinase 3 antibodies (subhazard ratio [sHR] 1.62 [95%
      confidence interval 1.39-1.89]) and cardiovascular involvement (sHR 1.59 [95%
      confidence interval 1.07-2.37]) were independently associated with a higher risk
      of relapse. Compared with patients with a creatinine level <=100 MUmoles/liter,
      patients with higher creatinine levels had a lower risk of relapse (sHR 0.81 [95%
      confidence interval 0.77-0.85] for a creatinine level of 101-200 MUmoles/liter;
      sHR 0.39 [95% confidence interval 0.22-0.69] for a creatinine level >200
      MUmoles/liter). CONCLUSION: Relapse of disease is common for patients with AAV. A
      creatinine level >200 MUmoles/liter at the time of diagnosis is strongly
      associated with a reduced risk of relapse and may help guide monitoring and
      treatment of patients with AAV.

PMID- 21953280
TI  - Relationship between total concentration and dilute HCl extraction of heavy
      metals in sediments of harbors and coastal areas in Korea.
AB  - Total concentrations of Cr, Ni, Cu, Zn, Cd and Pb in surface sediments were
      determined to investigate the regional trends of heavy metal contamination in 11
      coastal areas in Korea. Enrichment factor (EF) of heavy metals was calculated by
      comparing the level of their regional background. The averages of EF values in
      study areas were 0.99 for Cr, 1.05 for Ni, 4.23 for Cu, 1.80 for Zn, 3.92 for Cd
      and 1.54 for Pb, respectively. Dilute HCl extractions were useful to deduce the
      anthropogenic sources of heavy metals and the 1 M HCl extractable fractions of
      each metal varied from 0.3 to 37.3% for Cr, 1.9 to 66.3% for Ni, 4.2 to 92.9% for
      Cu, 7.1 to 99.7% for Zn, 10.9 to 98.9% for Cd and 15.0 to 99.1% for Pb. Comparing
      1 M HCl extractable fraction to total concentration, large portions of Cu, Zn, Cd
      and Pb were present as potentially bioavailable fractions from anthropogenic
      input and were significantly correlated with their EF values showing r > 0.68.

PMID- 21953281
TI  - Differences in physical activity among adults in households with and without
      children.
AB  - BACKGROUND: The study aim was to assess the relation of parent status to physical
      activity (PA) and the impact of parental roles, age and number of children on PA.
      METHODS: Data for 909 women and 965 men, aged 20-57, were analyzed. Mixed Models
      were used to assess differences in PA between parents and adults without
      children, with analyses stratified by sex. The primary outcome was accelerometer
      measured total daily minutes of moderate-to-vigorous PA (MVPA). RESULTS:
      Parenthood was not related to MVPA, but mothers reported more total PA than
      nonmothers. For mothers and fathers, self-reported household activity was higher
      and sitting time lower, compared with nonparents. Both men and women with
      children aged 0-5 reported the highest household activity and the lowest sitting
      time, with household PA higher and sitting time lower with more children. There
      was no evidence that leisure, transport, or occupational activity varied by
      parenthood. CONCLUSIONS: Considering the potential impact of child-rearing on
      parent time demands, there was little difference in parents' objectively measured
      MVPA compared with nonparents. Educational interventions or extracurricular
      programs for students and parents could target families with school-aged
      children. Development of tools to obtain parent reports of child care-specific PA
      behaviors would be useful.

PMID- 21953282
TI  - The human gallbladder secretes fibroblast growth factor 19 into bile: towards
      defining the role of fibroblast growth factor 19 in the enterobiliary tract.
AB  - Fibroblast growth factor 19 (FGF19) plays a crucial role in the negative feedback
      regulation of bile salt synthesis. In the postprandial state, activation of ileal
      farnesoid X receptor (FXR) by bile salts results in transcriptional induction of
      FGF19 and elevation of circulating FGF19 levels. An intestinal-liver axis of
      FGF19 signaling results in down-regulation of bile salt synthesis. The aim of
      this study was to explore a broader signaling activity of FGF19 in organs engaged
      in the enterohepatic circulation of bile salts. For this aim, FGF19 expression
      and aspects of FGF19 signaling were studied in surgical specimens and in cell
      lines of hepatobiliary and intestinal origin. FGF19 messenger RNA was found to be
      abundantly expressed in the human gallbladder and in the common bile duct, with
      only minor expression observed in the ileum. Interestingly, human gallbladder
      bile contains high levels of FGF19 (21.9 +/- 13.3 versus 0.22 +/- 0.14 ng/mL in
      the systemic circulation). Gallbladder explants secrete 500 times more FGF19 than
      FXR agonist-stimulated ileal explants. Factors required for FGF19 signaling
      (i.e., FGFR4 and betaKlotho) are expressed in mucosal epithelial cells of the
      gallbladder and small intestine. FGF19 was found to activate signaling pathways
      in cell lines of cholangiocytic, enteroendocrine, and enterocytic origin.
      CONCLUSION: The combined findings raise the intriguing possibility that biliary
      FGF19 has a signaling function in the biliary tract that differs from its
      established signaling function in the portal circulation. Delineation of the
      target cells in bile-exposed tissues and the affected cellular pathways, as well
      as a possible involvement in biliary tract disorders, require further studies.

PMID- 21953283
TI  - Is peak exposure to computer use a risk factor for neck and upper-extremity
      symptoms?
AB  - OBJECTIVES: Epidemiologic studies on physical exposure during computer use have
      mainly focused on average exposure duration. In this study, we aimed to relate
      periods of high peak exposure during computer use with the occurrence of neck
      shoulder (NS) and arm-wrist-hand (AWH) symptoms. METHODS: A prospective cohort
      study among 1951 office workers was carried out for two years, with periodical
      questionnaires and continuous measurements of computer input use. To define peak
      exposure, a distinction was made between peak days and weeks. Peak days were
      defined as days with a long duration of computer (ie, >=4 hours) or mouse use
      (ie, >=2.5 hours) or days with high frequency of mouse (ie, >=20 clicks per
      minute) or keyboard use (ie, >=160 keystrokes per minute). Weeks containing >=3
      peak days were considered peak weeks. Independent variables were numbers of peak
      days and peak weeks during a 3-month measurement period; dependent variables were
      self-reported NS and AWH symptoms during the following 3-month measurement
      period. RESULTS: Valid data were available for 2116 measurements of 774 office
      workers. No relation was found between any of the peak exposure parameters and
      AWH symptoms or with peak exposure in duration and NS symptoms. Most parameters
      referring to high frequency-related peak exposure were associated with less NS
      symptoms, but the effect estimates were very small and the confidence intervals
      close to the null. CONCLUSION: In this study, we found no indication that high
      peaks in computer use were related to the occurrence of NS or AWH symptoms.

PMID- 21953284
TI  - Hispanic adolescents coping with parental cancer.
AB  - AIM: The aim of this study was to identify the coping strategies Hispanic
      adolescents employed to deal with parental cancer, looking specifically at how
      gender and psychological symptoms such as depression and anxiety relate to such
      strategies. METHODS: Participants were 51 Puerto Rican adolescents who have a
      parent living with cancer. Adolescents completed a structured questionnaire with
      scales measuring depression (CES-D), anxiety (STAI), and coping strategies
      (COPE). RESULTS: The strategies used with the highest frequency were those
      generally viewed as positive and emotion-focused: emotional support, acceptance,
      and religion. The means for these coping strategies indicated that they occurred
      with high frequency. The findings revealed no differences in coping strategies
      between girls and boys. Depression was related to two maladaptive coping
      strategies: denial and behavioral disengagement; and one emotion-focused
      strategy: acceptance. Anxiety had significant correlations with one emotion
      focused strategy: acceptance; and two dysfunctional strategies: substance use and
      behavioral disengagement. The best predictors of adolescents' depression and
      anxiety were dysfunctional coping and problem-focused strategies. CONCLUSIONS:
      The study contributes to the knowledge about the coping strategies of Hispanic
      adolescents experiencing parental cancer and the importance of taking individual
      coping strategies into account when evaluating the impact of parental cancer on
      psychological well-being. This is especially true for adolescents who are likely
      to use dysfunctional strategies such as denial, substance use, and behavioral
      disengagement. Through psychosocial interventions, professionals need to assist
      these adolescents to improve and learn better coping strategies.

PMID- 21953285
TI  - The impact of randomization on the analysis of clinical trials.
AB  - The design of a comparative clinical trial involves a method of allocating
      treatments to patients. Usually, this assignment is performed to achieve several
      objectives: to minimize selection and accidental bias, to achieve balanced
      treatment assignment in order to maximize the power of the comparison, and most
      importantly, to obtain the basis for a valid statistical inference. In this
      paper, we are concerned exclusively with the last point. In our investigation, we
      will assume that measurements can be decomposed in a patient-specific effect, a
      treatment effect, and a measurement error. If the patient can be considered to be
      randomly drawn from a population, the randomization method does not affect the
      analysis. In fact, under this so-called population model, randomization would be
      unnecessary to obtain a valid inference. However, when individuals cannot be
      considered randomly selected, the patient effects may become fixed but unknown
      constants. In this case, randomization is necessary to obtain valid statistical
      analyses, and it cannot be precluded that the randomization method has an impact
      on the results. This paper elaborates that the impact can be substantial even for
      a two-sample comparison when a standard t-test is used for data analysis. We
      provide some theoretical results as well as simulations.

PMID- 21953286
TI  - Regulation of osteoclast function.
AB  - Osteoclasts are terminally differentiated multinucleated cells that are the
      principal resorptive cells of bone, playing a central role in the formation of
      the skeleton and regulation of its mass. The molecular events involved in the
      differentiation and function of osteoclasts had not been clarified for a long
      time. Over the past two decades, several novel approaches have been developed and
      adopted to investigate osteoclast biology. In the present review, we would like
      to update recent progress in the elucidation of the molecular mechanism of
      osteoclast activation and function.

PMID- 21953287
TI  - Value of serum IgG4 in the diagnosis of IgG4-related disease and in
      differentiation from rheumatic diseases and other diseases.
AB  - IgG4-related disease (IgG4-RD) is a novel disease entity that includes Mikulicz's
      disease, autoimmune pancreatitis (AIP), and many other conditions. It is
      characterized by elevated serum IgG4 levels and abundant IgG4-bearing plasmacyte
      infiltration of involved organs. We postulated that high levels of serum IgG4
      would comprise a useful diagnostic tool, but little information is available
      about IgG4 in conditions other than IgG4-RD, including rheumatic diseases.
      Several reports have described cutoff values for serum IgG4 when diagnosing IgG4
      RD, but these studies mostly used 135 mg/dL in AIP to differentiate from
      pancreatic cancer instead of rheumatic and other common diseases. There is no
      evidence for a cutoff serum IgG4 level of 135 mg/dL for rheumatic diseases and
      common diseases that are often complicated with rheumatic diseases. The aim of
      this work was to re-evaluate the usual cutoff serum IgG4 value in AIP (135 mg/dL)
      that is used to diagnose whole IgG4-RD in the setting of a rheumatic clinic by
      measuring serum IgG4 levels in IgG4-RD and various disorders. We therefore
      constructed ROC curves of serum IgG4 levels in 418 patients who attended Sapporo
      Medical University Hospital due to IgG4-RD and various rheumatic and common
      disorders. The optimal cut-off value of serum IgG4 for a diagnosis of IgG4-RD was
      144 mg/dL, and the sensitivity and specificity were 95.10 and 90.76%,
      respectively. Levels of serum IgG4 were elevated in IgG4-RD, Churg-Strauss
      syndrome, multicentric Castleman's disease, eosinophilic disorders, and in some
      patients with rheumatoid arthritis, systemic sclerosis, chronic hepatitis, and
      liver cirrhosis. The usual cut-off value of 135 mg/dL in AIP is useful for
      diagnosing whole IgG4-RD, but high levels of serum IgG4 are sometimes observed in
      not only IgG4-RD but also other rheumatic and common diseases.

PMID- 21953288
TI  - Effects of usnic acid exposure on human hepatoblastoma HepG2 cells in culture.
AB  - Usnic acid, a natural botanical product, is a constituent of some dietary
      supplements used for weight loss. It has been associated with clinical
      hepatotoxicity leading to liver failure in humans. The present study was
      undertaken for metabolism and toxicity evaluations of usnic acid in human
      hepatoblastoma HepG2 cells in culture. The cells were treated with the vehicle
      control and usnic acid at concentrations of 0-100 um for 24 h at 37  degrees C in
      5% CO2 . Following the treatment period, the cells were evaluated by biochemical
      and toxicogenomic endpoints of toxicity that included cytochrome P450 activity,
      cytotoxicity, oxidative stress, mitochondrial dysfunction and changes in pathway
      focused gene expression profiles. Usnic acid exposure resulted in increased P450
      activity, cytotoxicity, oxidative stress and mitochondrial dysfunction in HepG2
      cells. The pathway-focused gene expression analysis resulted in significantly
      altered expression of six genes out of a total of 84 genes examined. Of the six
      altered genes, three genes were up-regulated and three genes down-regulated. A
      marked up-regulation of one gene CCL21 associated with inflammation, one gene
      CCNC associated with proliferation and carcinogenesis and one gene UGT1A4
      associated with metabolism as well as DNA damage and repair were observed in the
      usnic acid-treated cells compared with the vehicle control. Also a marked down
      regulation of one gene CSF2 associated with inflammation and two genes (CYP7A1
      and CYP2E1) associated with oxidative metabolic stress were observed in the usnic
      acid-treated cells compared with the control. The biomarkers used in this study
      demonstrate the toxicity of usnic acid in human hepatoblastoma HepG2 cells,
      suggesting an oxidative mechanism of action.

PMID- 21953289
TI  - Immunization with Porphyromonas gingivalis enolase induces autoimmunity to
      mammalian alpha-enolase and arthritis in DR4-IE-transgenic mice.
AB  - OBJECTIVE: To examine the hypothesis that the subset of rheumatoid arthritis (RA)
      characterized by antibodies to citrullinated alpha-enolase is mediated by
      Porphyromonas gingivalis enolase in the context of DR4 alleles. METHODS:
      Recombinant human alpha-enolase and P gingivalis enolase, either citrullinated or
      uncitrullinated, were used to immunize DR4-IE-transgenic mice and control mice
      (class II major histocompatibility complex-deficient [class II MHC(-/-)] and
      C57BL/6 wild-type mice). Arthritis was quantified by measurement of ankle
      swelling in the hind paws and histologic examination. Serum IgG reactivity with
      alpha-enolase and citrullinated alpha-enolase was assayed by Western blotting and
      enzyme-linked immunosorbent assay (ELISA). Antibodies to peptide 1 of
      citrullinated alpha-enolase (CEP-1) and its arginine-bearing control peptide, REP
      1, were also assessed by ELISA. RESULTS: Significant hind-ankle swelling (>=0.3
      mm) occurred in DR4-IE-transgenic mice immunized with citrullinated human alpha
      enolase (9 of 12 mice), uncitrullinated human alpha-enolase (9 of 12 mice),
      citrullinated P gingivalis enolase (6 of 6 mice), and uncitrullinated P
      gingivalis enolase (6 of 6 mice). Swelling peaked on day 24. None of the control
      groups developed arthritis. The arthritic joints showed synovial hyperplasia and
      erosions, but there was a paucity of leukocyte infiltration. Antibodies to human
      alpha-enolase, both citrullinated and unmodified, and to CEP-1 and REP-1 were
      detectable in all immunized mice except the class II MHC(-/-) control mice.
      CONCLUSION: This is the first animal model that links an immune response to P
      gingivalis enolase to an important subset of RA, defined by antibodies to
      citrullinated alpha-enolase in the context of DR4. The fact that arthritis and
      anti-CEP-1 antibodies were induced independent of citrullination of the
      immunizing antigen suggests that the unmodified form of alpha-enolase may be
      important in initiating the corresponding subset of human RA.

PMID- 21953290
TI  - Significant damage-rescuing effects of wood vinegar extract in living
      Caenorhabditis elegans under oxidative stress.
AB  - BACKGROUND: Wood vinegar (WV), a byproduct from the charcoal production process,
      has been reported to have excellent antioxidant capability by chemical
      examination. However, the biological effect of WV in living animals is still
      unknown. In this study, a simple model organism, the nematode Caenorhabditis
      elegans, was used as an in vivo system to assess the biological effects of wood
      vinegar through the development, lifespan, brood size, germline cell apoptosis
      and superoxide dismutase (SOD) level. RESULTS: Wood vinegar extract (WVE)
      promoted the development, prolonged the lifespan and increased the brood size in
      reactive oxidative species (ROS)-sensitive mutant worms. WVE treatment rescued
      the effects of damage in germline cell apoptosis and SOD upregulation induced by
      paraquat, an ROS generator, to the control level. Additionally, WVE showed
      comparative ability in rescuing damage as compared with L-ascorbic acid and alpha
      tocopherol. CONCLUSION: WVE treatment exhibits a remedial/beneficial effect on
      ROS-sensitive mutant under normal cultural conditions and on wild-type worms
      under oxidative stress. ROS scavenging is involved in the damage-rescuing
      mechanism. This study will provide a basal biological and nutritional exploration
      for the use of WV as a functional food, and for the substitution of chemical
      antioxidants with side effects in food.

PMID- 21953291
TI  - Postchemotherapy histological analysis of major intrahepatic vessels for reversal
      of attachment or invasion by colorectal liver metastases.
AB  - BACKGROUND: Although tumor reduction via present-day prehepatectomy chemotherapy
      can render initially unresectable disease potentially resectable, little is known
      about the effects of such chemotherapy on liver metastases with known attachment
      to or invasion of major intrahepatic vessels. We histologically assessed the
      relationships of liver tumors to major intrahepatic vessels after chemotherapy.
      METHODS: In 45 patients who underwent chemotherapy and hepatectomy with
      pretreatment images showing metastases attached to or invading major intrahepatic
      vessels, 77 metastases showed attachment to or invasion of 96 vessels. RESULTS:
      Using postchemotherapy imaging, 11 of 77 metastases (14.3%) appeared separated
      from 12 of 96 major hepatic vessels (12.5%). Among 83 vessels later examined
      pathologically, 29 showed direct invasion (35%) and 10 showed attachment (12%).
      Tumors involved another 9 vessels (11%) that were separated surgically from the
      tumor and preserved during hepatectomy. Tumor attachment that exceeded 25% of
      vessel circumferences via imaging after chemotherapy was a factor associated with
      pathological vascular invasion or attachment according to multivariate analysis
      (relative risk, 8.449; 95% confidence interval, 1.961-36.415; P = .0042).
      CONCLUSIONS: Liver metastasis attachment to or invasion of major intrahepatic
      vessels is difficult to eradicate even with otherwise effective chemotherapy.

PMID- 21953292
TI  - Effect of magnetic fields on antioxidative defense and fitness-related traits of
      Baculum extradentatum (insecta, phasmatodea).
AB  - This study aimed to determine the effect of magnetic fields on the antioxidative
      defense and fitness-related traits of Baculum extradentatum. Following exposure
      to magnetic fields, antioxidative defense (superoxide dismutase (SOD), catalase
      (CAT) activities, and total glutathione (GSH) content) and fitness-related traits
      (egg mortality, development dynamics, and mass of nymphs) were monitored in
      nymphs. The experimental groups were: control (kept out of influence of the
      magnets), a group exposed to a constant magnetic field (CMF) of 50 mT, and a
      group exposed to an alternating magnetic field (AMF) of 50 Hz, 6 mT. We found
      increased SOD and CAT activities in animals exposed to constant and AMFs, whereas
      GSH activity was not influenced by experimental magnetic fields. No differences
      were found in egg mortality between control and experimental groups. Significant
      differences in the time of development between the control and the CMF group were
      observed, as well as between the CMF and the AMF group. No differences were found
      in the mass of the nymphs between the three experimental groups. In conclusion,
      CMF and AMF have the possibility to modulate the antioxidative defense and some
      of the fitness-related traits in B. extradentatum.

PMID- 21953293
TI  - Global microRNA expression profiling of microdissected tissues identifies miR
      135b as a novel biomarker for pancreatic ductal adenocarcinoma.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is known for its poor prognosis resulting
      from being diagnosed at an advanced stage. Accurate early diagnosis and new
      therapeutic modalities are therefore urgently needed. MicroRNAs (miRNAs),
      considered a new class of biomarkers and therapeutic targets, may be able to
      fulfill those needs. Combining tissue microdissection with global miRNA array
      analyses, cell type-specific miRNA expression profiles were generated for normal
      pancreatic ductal cells, acinar cells, PDAC cells derived from xenografts and
      also from macrodissected chronic pancreatitis (CP) tissues. We identified 78
      miRNAs differentially expressed between ND and PDAC cells providing new insights
      into the miRNA-driven pathophysiological mechanisms involved in PDAC development.
      Having filtered miRNAs which are upregulated in the three pairwise comparisons of
      PDAC vs. ND, PDAC vs. AZ and PDAC vs. CP, we identified 15 miRNA biomarker
      candidates including miR-135b. Using relative qRT-PCR to measure miR-135b
      normalized to miR-24 in 75 FFPE specimens (42 PDAC and 33 CP) covering a broad
      range of tumor content, we discriminated CP from PDAC with a sensitivity and
      specificity of 92.9% [95% CI=(80.5, 98.5)] and 93.4% [95% CI=(79.8, 99.3)],
      respectively. Furthermore, the area under the curve (AUC) value reached of 0.97
      was accompanied by positive and negative predictive values of 95% and 91%,
      respectively. In conclusion, we report pancreatic cell-specific global miRNA
      profiles, which offer new candidate miRNAs to be exploited for functional studies
      in PDAC. Furthermore, we provide evidence that miRNAs are well-suited analytes
      for development of sensitive and specific aid-in-diagnosis tests for PDAC.

PMID- 21953294
TI  - hsp70 mRNA temporal localization in rat skeletal myofibers and blood vessels post
      exercise.
AB  - Rapid transcription of the survival transcript, inducible heat shock protein 70
      (hsp70), is critical for mounting cytoprotection against severe cellular stress,
      like elevated temperature. Previous investigations have demonstrated that
      exercise-induced expression of Hsp70 protein occurs in a fiber-specific pattern;
      however, the activation pattern of hsp70 mRNA expression remains unclear in
      skeletal muscle. Consequentially, the temporal localization of hsp70 mRNA was
      characterized via in situ hybridization (ISH) experiments examining fast-muscle,
      white vastus: 1, 3, 10, and 24 h after a single bout of intense treadmill running
      (1 h, 30 m/min, 6% grade) in rats. The role that the physiologic temperature
      stress associated with exercise (raising core body temperature to 40.0 degrees C
      for 15 min (HS-40.0 degrees C)) might play in inducing hsp70 mRNA expression was
      also explored. In skeletal muscle myofibers (SkM), hsp70 mRNA ISH signal was
      observed to be concentrated in a punctate manner that was associated with nuclei
      post-exercise. HS-40 degrees C treatment produced minimal detectable hsp70 mRNA
      ISH signal in SkM. In large intermyofibrillar blood vessels (BV), peak hsp70 mRNA
      signal, distributed throughout the vessel wall, was observed 1 h post-exercise.
      In BV, no differences in hsp70 mRNA signal were observed between HS-40 degrees C
      and EX-1 h. Results indicate that the majority of hsp70 mRNA is retained in a
      perinuclear localization in SkM post-exercise. They further suggest a muscle-type
      specific time course for peak hsp70 mRNA expression. This investigation suggests
      that the physiologic rise in core temperature associated with exercise per se is
      not the key stimulus responsible for inducing hsp70 mRNA transcription in SkM.

PMID- 21953296
TI  - Magnetosomes on surface: an imaging study approach.
AB  - In this study, we deposited isolated magnetosomes from magnetotactic bacteria
      Magnetospirillum strain AMB-1 onto solid surfaces using spin coating (SC) and
      drop coating (DC) techniques. Four imaging techniques have been used to visualize
      the sample structure: scanning and transmission electron microscopy (SEM, TEM),
      atomic and magnetic force microscopy (AFM, MFM). Additionally, dynamic light
      scattering was applied to measure the hydrodynamic radius of
      agglomerated/aggregated magnetosomes in a liquid environment. This manuscript
      discusses observed differences between structures obtained by two deposition
      techniques, i.e. possible interactions and factors responsible for magnetosomes'
      formation, their morphology on surfaces as a result of agglomeration and
      aggregation phenomena. Moreover, topography and homogeneity of obtained
      structures as well as thickness of protein-based membrane were also examined and
      described. Using high-resolution TEM, we analyzed the size of magnetic cores,
      their crystal structure and quality. We found that the SC technique provides a
      homogenous layer of magnetosomes and hydrophilization of silicon surfaces
      improves the deposition of magnetosomes. However, due to strong hydrogen
      interaction to the hydrophilic silicone surface, the organic membrane of
      magnetosomes is mostly flattened. As a matter of fact, the size distributions of
      magnetosomes deposited by SC and DC techniques (logarithmic-normal tendency)
      differ from the Feret diameter distribution (normal). Furthermore, our study
      confirms the good crystalline quality of magnetosomes' cores. It also shows that
      they are magnetic in the all their volume.

PMID- 21953297
TI  - Nuclear lamins and laminopathies.
AB  - Nuclear lamins are intermediate filament proteins that polymerize to form the
      nuclear lamina on the inner aspect of the inner nuclear membrane. Long known to
      be essential for maintaining nuclear structure and disassembling/reassembling
      during mitosis in metazoans, research over the past dozen years has shown that
      mutations in genes encoding nuclear lamins, particularly LMNA encoding the A-type
      lamins, cause a broad range of diverse diseases, often referred to as
      laminopathies. Lamins are expressed in all mammalian somatic cells but mutations
      in their genes lead to relatively tissue-selective disease phenotypes in most
      cases. While mutations causing laminopathies have been shown to produce
      abnormalities in nuclear morphology, how these disease-causing mutations or
      resultant alterations in nuclear structure lead to pathology is only starting to
      be understood. Despite the incomplete understanding of pathogenic mechanisms
      underlying the laminopathies, basic research in cellular and small animal models
      has produced promising leads for treatments of these rare diseases.

PMID- 21953298
TI  - Asymmetric properties of long-term and total heart rate variability.
AB  - We report on two new physiological phenomena: the long-term and total heart rate
      asymmetry, which describe a significantly larger contribution of heart rate
      accelerations to long-term and total heart rate variability. In addition to the
      existing pair of indices, SD1(d); SD1(a); which are based on partitioning short
      term variance, we introduce two other pairs of descriptors based on partitioning
      longterm (SD2(d); SD2(a)) and total (SDNN(d); SDNN(a)) heart rate variability.
      The new asymmetric descriptors are used to analyze RR intervals time series
      derived from the 30-min ECG recordings of 241 healthy subjects resting in supine
      position. It is shown that both new types of asymmetry are present in 76% of the
      subjects. The new phenomena reported here are real physiological findings rather
      than artifacts of the method since they vanish after data shuffling.

PMID- 21953299
TI  - Identification of osteopontin as a novel marker for early hepatocellular
      carcinoma.
AB  - The aim of this study was to identify a biomarker that could improve alpha
      fetoprotein (AFP) performance in hepatocellular carcinoma (HCC) surveillance
      among patients with cirrhosis. We performed proteomic profiling of plasma from
      patients with cirrhosis or HCC and validated selected candidate HCC biomarkers in
      two geographically distinct cohorts to include HCC of different etiologies. Mass
      spectrometry profiling of highly fractionated plasma from 18 cirrhosis and 17 HCC
      patients identified osteopontin (OPN) as significantly up-regulated in HCC cases,
      compared to cirrhosis controls. OPN levels were subsequently measured in 312
      plasma samples collected from 131 HCC patients, 76 cirrhosis patients, 52 chronic
      hepatitis C (CHC) and B (CHB) patients, and 53 healthy controls in two
      independent cohorts. OPN plasma levels were significantly elevated in HCC
      patients, compared to cirrhosis, CHC, CHB, or healthy controls, in both cohorts.
      OPN alone or in combination with AFP had significantly better area under the
      receiver operating characteristic curve, compared to AFP, in comparing cirrhosis
      and HCC in both cohorts. OPN overall performance remained higher than AFP in
      comparing cirrhosis and the following HCC groups: HCV-related HCC, HBV-associated
      HCC, and early HCC. OPN also had a good sensitivity in AFP-negative HCC. In a
      pilot prospective study including 22 patients who developed HCC during follow-up,
      OPN was already elevated 1 year before diagnosis. CONCLUSION: OPN was more
      sensitive than AFP for the diagnosis of HCC in all studied HCC groups. In
      addition, OPN performance remained intact in samples collected 1 year before
      diagnosis.

PMID- 21953300
TI  - Intravitreal bevacizumab for severe vaso-occlusive retinopathy in systemic lupus
      erythematosus.
AB  - Severe vaso-occlusive retinopathy is a relatively rare form of retinopathy in
      systemic lupus erythematosus (SLE). We report two patients with severe vaso
      occlusive retinopathy in SLE who were treated with intravitreal bevacizumab
      (IVB). (Patient 1) A 35-year-old woman presented with left visual loss and was
      diagnosed with SLE after systemic evaluation. Despite systemic immunosuppressive
      therapy, retinal vascular obstruction progressed and neovascularization of the
      disk (NVD) developed. The patient was treated with IVB and pan retinal
      photocoagulation. The progression of vascular obstruction ceased and regressed.
      (Patient 2) A 24-year-old man with SLE presented with left visual loss. There was
      retinal vascular obstruction with macular edema in both eyes, and then the
      patient was treated with IVB. One month after injection, minimal capillary
      nonperfusion increased to 10 disk area, and 5 months later, neovascularization
      elsewhere (NVE) developed in the right eye. Six months after injection, vitreous
      hemorrhage with florid NVE and NVD developed in the left eye. In selected severe
      vaso-occlusive retinopathy in SLE patients, IVB may be an adjuvant option for
      treatment.

PMID- 21953301
TI  - Reliability and efficacy of the new massage technique on the treatment in the
      patients with carpal tunnel syndrome.
AB  - We aimed to bring a more understandable and applicable technique to the
      literature instead of "massage therapy" in CTS. We compared our new technique
      with the splint wear, of which the efficacy in CTS has been proven with many
      studies. Eighty-four patients between 31 and 65 years of age were included in the
      study. The patients were divided into two equal groups. In the first group,
      splint and "Madenci" hand massage technique were applied, and in the second group
      only splint was applied. A splint was provided for all patients with tendon and
      nerve gliding exercises, and also when needed analgesic drugs were given. When
      the pretreatment and posttreatment parameters were compared via repetitive
      measurement analysis, it was found that PGA and MDPGA were significantly
      decreased in both groups (P = 0.001), whereas grip strength was significantly
      increased (P = 0.001). While no statistically significant difference was found
      between the groups regarding pretreatment values (P > 0.05), the posttreatment
      PGA, MDPGA, and grip strength scores were significantly improved in Group I
      compared to Group II (P < 0.05). To the best our knowledge, the present study is
      the first and largest study in the literature conducted on the massage technique
      that will contribute to the treatment of CTS. As this new massage technique is
      easy for self-application, cheap, and practical, every patient with CTS can apply
      the massage to him/herself easily.

PMID- 21953303
TI  - Three cases of fever of unknown origin (FUO) with acute multifocal non-bacterial
      osteitis (NBO) as reactive osteomyelitis.
AB  - Evaluation for fever of unknown origin (FUO) requires a long list of studies.
      Recently, the validity of PET scan in FUO evaluation has been approved for
      screening and qualification. Non-bacterial osteitis (NBO) refers to non-bacterial
      and non-specific inflammation of bone, which is usually chronic, and involves
      multiple bony sites. We have experienced 3 cases of FUO associated with increased
      symmetric multiple fluorodeoxyglucose uptake preferentially at the epiphysis of
      the femur and tibia on fusion Positron emission tomography/Computed tomography
      (PET/CT). Patients were young women, who complained of intermittent fever lasting
      several months, which was associated only with neutropenia and relative
      lymphocytosis. Bone biopsies revealed increased lymphocytes and histiocyte
      infiltration of the cortical bone with reactive bone marrow. With no evidence of
      infection, the fever showed spontaneous remission within 2 weeks of conservative
      treatment. We report on 3 cases of FUO with self-limited acute NBO as reactive
      osteomyelitis and suggest that this unique pattern on PET/CT would be helpful for
      FUO evaluation.

PMID- 21953302
TI  - Understanding rheumatic fever.
AB  - Through a comprehensive review of the recent findings on rheumatic fever, we
      intend to propose a new physiopathologic model for this disease. A Medline search
      was performed for all articles containing the terms rheumatic fever or rheumatic
      heart disease in title or abstract from 1970 to 2011. Best evidence qualitative
      technique was used to select the most relevant. The scientific interest on
      rheumatic fever has notably diminished throughout the twentieth century as
      evidenced by the comparison of the proportion of articles in which RF was a
      subject in 1950 (0.26%) and today (0.03%) [Pubmed]. However, RF remains a major
      medical and social problem in the developing world and in the so-called hotspots,
      where it still causes around 500.000 deaths each year, not too different from the
      pre-antibiotic era. The role of genetic factors in RF susceptibility is
      discussed. Familiar aggregation, similarity of disease patterns between siblings,
      identical twin, and HLA correlation studies are evidence for a genetic influence
      on RF susceptibility. The suspect-involved genes fall mainly into those capable
      of immunologic mediation. Molecular mimicry explains the triggering of RF, but an
      intense and sustained inflammation is needed to cause sequels. Also, RF patients
      vary greatly in terms of symptoms. It is likely that a genetic background
      directing immune response towards a predominantly Th1 or Th2 pattern contributes
      to these features. The recent findings on rheumatic fever provide important
      insight on its physiopathology that helps understanding this prototype post
      infectious autoimmune disease giving insights on other autoimmune conditions.

PMID- 21953304
TI  - Development of a novel recombinant biotherapeutic with applications in targeted
      therapy of human arthritis.
AB  - OBJECTIVE: To isolate recombinant antibodies with specificity for human arthritic
      synovium and to develop targeting reagents with joint-specific delivery capacity
      for therapeutic and/or diagnostic applications. METHODS: In vivo single-chain Fv
      (scFv) antibody phage display screening using a human synovial xenograft model
      was used to isolate antibodies specific to the microvasculature of human
      arthritic synovium. Single-chain Fv antibody tissue-specific reactivity was
      assessed by immunostaining of synovial tissues from normal controls and from
      patients with rheumatoid arthritis and osteoarthritis, normal human tissue
      arrays, and tissues from other patients with inflammatory diseases displaying
      neovasculogenesis. In vivo scFv antibody tissue-specific targeting capacity was
      examined in the human synovial xenograft model using both (125)I-labeled and
      biotinylated antibody. RESULTS: We isolated a novel recombinant human antibody,
      scFv A7, with specificity for the microvasculature of human arthritic synovium.
      We showed that in vivo, this antibody could efficiently target human synovial
      microvasculature in SCID mice transplanted with human arthritic synovial
      xenografts. Our results demonstrated that scFv A7 antibody had no reactivity with
      the microvasculature or with other cellular components found in a comprehensive
      range of normal human tissues including normal human synovium. Further, we showed
      that the reactivity of the scFv A7 antibody was not a common feature of
      neovasculogenesis associated with chronic inflammatory conditions. CONCLUSION:
      Here we report for the first time the identification of an scFv antibody, A7,
      that specifically recognizes an epitope expressed in the microvasculature of
      human arthritic synovium and that has the potential to be developed as a joint
      specific pharmaceutical.

PMID- 21953305
TI  - The impact of misclassification due to survey response fatigue on estimation and
      identifiability of treatment effects.
AB  - Response fatigue can cause measurement error and misclassification problems in
      survey research. Questions asked later in a long survey are often prone to more
      measurement error or misclassification. The response given is a function of both
      the true response and participant response fatigue. We investigate the
      identifiability of survey order effects and their impact on estimators of
      treatment effects. The focus is on fatigue that affects a given answer to a
      question rather than fatigue that causes non-response and missing data. We
      consider linear, Gamma, and logistic models of response that incorporate both the
      true underlying response and the effect of question order. For continuous data,
      survey order effects have no impact on study power under a Gamma model. However,
      under a linear model that allows for convergence of responses to a common mean,
      the impact of fatigue on power will depend on how fatigue affects both the rate
      of mean convergence and the variance of responses. For binary data and for less
      than a 50% chance of a positive response, order effects cause study power to
      increase under a linear probability (risk difference) model but decrease under a
      logistic model. The results suggest that measures designed to reduce survey order
      effects might have unintended consequences. We present a data example that
      demonstrates the problem of survey order effects.

PMID- 21953306
TI  - Small-vessel vasculitis surrounding an uninflamed temporal artery and isolated
      vasa vasorum vasculitis of the temporal artery: two subsets of giant cell
      arteritis.
AB  - OBJECTIVE: To evaluate the frequency and clinical characteristics of
      periadventitial small-vessel vasculitis (SVV) and isolated vasa vasorum
      vasculitis (VVV). METHODS: We identified 455 temporal artery biopsies performed
      in residents of Reggio Emilia, Italy between 1986 and 2003. Slides of temporal
      artery biopsy specimens were reviewed by a pathologist who was blinded with
      regard to clinical data. SVV was defined as inflammation of the small vessels
      external to the temporal artery adventitia, and VVV was defined as isolated
      inflammation of temporal artery vasa vasorum. Medical records of patients with
      SVV and/or VVV were reviewed, and demographic, clinical, laboratory, and followup
      data were collected. For comparison purposes, we collected the same data from an
      equal number of randomly selected patients with evidence of classic giant cell
      arteritis (GCA). RESULTS: Sixteen patients had SVV, 18 had isolated VVV, and 5
      had both SVV and VVV. Compared with patients with classic GCA, the frequencies of
      headache, scalp tenderness, abnormalities of temporal arteries, jaw claudication,
      anorexia, and weight loss, the levels of acute-phase reactant at diagnosis, and
      the initial and cumulative doses prednisone were significantly lower and the
      frequency of peripheral synovitis was higher in the patients with SVV, and the
      frequency of cranial ischemic events was similar in the 2 groups. In contrast,
      the clinical characteristics and erythrocyte sedimentation rate at diagnosis of
      patients with isolated VVV were similar to those of patients with classic GCA.
      CONCLUSION: Our findings indicate that isolated VVV and SVV should be considered
      part of the histopathologic spectrum of GCA.

PMID- 21953307
TI  - Organophosphorus pesticides residues in fish samples from the River Nile
      tributaries in Egypt.
AB  - The concentration of organophosphorus pesticides in fish samples from different
      tributaries of the Nile River in Egypt was monitored. Fish samples were collected
      from El Menofiya, canal water supplies (El-Sarsawia, El-Bagoria and Bahr Shebin),
      in addition to El-Embaby, El-Menofi and Miet Rabiha drainage canals each 2 month
      during periods of 16 month, June 2007-Septemper 2008. Chloropyrifos, cadusafos,
      diazinon, prothiphos and malathion were detected in fish tissues samples at level
      below the maximum residue limit. The highest average amount of chlorpyrifos (9.38
      ng g(-1)) and malathion (8.31 ng g(-1)) were detected in El-Embaby drain.
      Prothiphos were found in tissues collected from El-Sarsawia canal and Miet-Rabiha
      drain at mean concentration of 4.91 and 6.55 ng g(-1), respectively. Diazinon was
      only found in one fish sample that collected from El-Menofi drain at the level of
      9.23 ng g(-1).

PMID- 21953308
TI  - Neurodevelopment of infants with prenatal exposure to polybrominated diphenyl
      ethers.
AB  - The study aimed to examine the impact of prenatal exposure to polybrominated
      diphenyl ethers (PBDEs) on infant neurodevelopment. PBDEs levels in 36 cord blood
      samples were analyzed with a high-resolution-gas-chromatograph/high-resolution
      mass-spectrometer and infant neurodevelopment was assessed using the Bayley
      Scales of Infant and Toddler Development, Third Edition. The mean and median of
      Sigma(11)PBDEs were 6.63 and 4.63 ng/g lipid, respectively. As compared to the
      lower PBDEs group (Sigma(11)PBDEs < 4.63 ng/g lipid), the higher PBDEs group
      (Sigma(11)PBDEs > 4.63 ng/g lipid) had a significantly higher actual odds ratio
      (OR = 1.13, p < 0.05) of the cognition score as well as a lower odds ratio (OR =
      0.904, p < 0.01) of the adaptive behavior score, suggesting that prenatal PBDEs
      exposure may potentially affect infant neurodevelopment.

PMID- 21953309
TI  - Unusual combination of bilateral testicular microlithiasis and tubular ectasia of
      the rete testis with left intra- and extratesticular varicocele in a 17-year-old
      boy.
AB  - We describe the rare combination of testicular microlithiasis, unilateral
      intra/extratesticular varicocele, and tubular ectasia of the rete testis in a 17
      year-old boy who presented with testicular pain following a trauma. He had a
      prior history of undescended testis and orchiopexy in childhood. His workup
      included a normal abdominal ultrasound and a sperm analysis demonstrating a low
      sperm count with sperm dysmotility. A follow-up ultrasound was unchanged, and he
      has been managed conservatively. This combined set of findings has not been
      previously reported.

PMID- 21953310
TI  - Heart rate variability and endothelial function after sleep deprivation and
      recovery sleep among male shift and non-shift workers.
AB  - OBJECTIVES: Endothelial dysfunction and alterations in heart rate variability
      (HRV) as well as sleep deprivation and shift work have been associated with
      cardiovascular disease. The aim of this study was to compare HRV and endothelial
      function among shift and matched non-shift workers in response to total sleep
      deprivation and recovery sleep under identical laboratory settings. METHODS:
      Eleven experienced male shift workers (shift work >= 5 years) and 14 non-shift
      workers were matched for age, body mass index, and cholesterol. HRV parameters
      [eg, HR variance and low frequency/high frequency (LF/HF) ratio] were derived
      from 5-minute electrocardiogram bins at 0.25, 4.25, 11.5, 12.5, and 13.5 hours
      after habitual wake-up time and endothelial function was assessed by flow
      mediated dilatation (FMD) using ultrasound at 0.75 and 10.75 hours after habitual
      wake-up time, following baseline sleep, total sleep deprivation, and recovery
      sleep (posture- and food-controlled throughout). Circadian phase was assessed
      before baseline sleep by salivary dim light melatonin onset. RESULTS: There was
      no difference in circadian phase between shift and non-shift workers. HR variance
      was highest at 0.25 hours following total sleep deprivation and lowest after
      recovery sleep. A significantly higher LF/HF ratio, significantly lower HR
      variance, and a trend for a lower %FMD (P=0.08) were observed among shift
      compared to non-shift workers. CONCLUSION: Despite similar demographics,
      circadian phase, posture and food intake, differences in endothelial function and
      HRV were observed in the two groups, which may reflect higher sympathetic and/or
      lower parasympathetic activity, contributing to increased cardiovascular risk
      among the shift workers.

PMID- 21953311
TI  - Predictors of adherence to supervised and unsupervised exercise in the Alberta
      Physical Activity and Breast Cancer Prevention Trial.
AB  - BACKGROUND: Few studies have examined the predictors of adherence separately for
      supervised and unsupervised exercise or in postmenopausal women over an extended
      time period. Here, we report the predictors of exercise adherence in the Alberta
      Physical Activity and Breast Cancer Prevention (ALPHA) Trial. METHODS: The ALPHA
      trial randomized 160 postmenopausal women in Calgary and Edmonton, Canada to an
      exercise intervention that consisted of an average of 200 min/wk of supervised
      (123 minutes) and unsupervised (77 minutes) exercise over a 1-year period.
      Baseline data were collected on demographic, health-related fitness, quality of
      life, and motivational variables from the theory of planned behavior. RESULTS:
      Participants completed an average of 95% of their supervised exercise and 79% of
      their unsupervised exercise. In multivariate analyses, 8.1% (P=.001) of the
      variance was explained for supervised exercise by being from Edmonton (beta=0.22;
      P=.004) and older (beta=0.15; P=.050). For unsupervised exercise, 21.1% (P<.001)
      of the variance was explained by being from Calgary (beta=-0.39; P<.001), having
      a family history of breast cancer (beta=0.21; P=.003), and having higher vitality
      (beta=0.19; P=.011). CONCLUSIONS: Predictors of adherence may differ for
      supervised and unsupervised exercise, moreover, predicting adherence to
      supervised exercise may be particularly difficult in well-controlled efficacy
      trials.

PMID- 21953312
TI  - Starch determination, amylose content and susceptibility to in vitro amylolysis
      in flours from the roots of 25 cassava varieties.
AB  - BACKGROUND: Cassava cultivars are classified following different criteria, such
      as cyanogenic glucoside content or starch content. Here, flours from the roots of
      25 cassava varieties cultivated simultaneously in a single plantation, were
      characterized in terms of starch content (SC), amylose content (AC), alpha
      amylolysis index (AI) and gel formation ability. Resistant starch content (RS)
      was measured in 10 of the samples. RESULTS: Cassava flours exhibited high SC, low
      AC and low AI values, with differences among varieties. Cluster analysis based on
      these parameters divided the cultivars in four groups differing mainly in SC and
      AC. AI and AC were inversely correlated (r = -0.59, P < 0.05) in 18 of the
      cultivars, suggesting AC as an important factor governing the susceptibility to
      enzymatic hydrolysis of starch in raw cassava. Differences in susceptibility to
      amylolysis, assessed by RS, were also recorded in the sample subset analyzed.
      Most flours yielded pastes or gels upon heating and cooling. Gels differed in
      their subjective grade of firmness, but none exhibited syneresis, confirming the
      low retrogradation proclivity of cassava starch. CONCLUSION: Some differences
      were found among cassava samples, which may be ascribed to inter-cultivar
      variation. This information may have application in further agronomic studies or
      for developing industrial uses for this crop.

PMID- 21953313
TI  - Differential effects of nutritional and non-nutritional therapies on intestinal
      barrier function in an in vitro model.
AB  - BACKGROUND: Diminished intestinal epithelial barrier function contributes to the
      pathogenesis of Crohn's disease. Clinical and experimental studies propose that
      increased tumor necrosis factor (TNF)-alpha promotes barrier dysfunction. The aim
      of this study was to investigate the effects of nutritional and other therapies
      upon intestinal barrier function in the presence of TNF-alpha in an in vitro
      model. METHODS: Caco-2 monolayers were grown to confluence on membrane supports
      and then exposed to TNF-alpha in the presence of polymeric formula,
      hydrocortisone or infliximab. Monolayer permeability was evaluated by measuring
      epithelial resistance, short-circuit current and horseradish peroxidase flux in
      an Ussing chamber. Tight junction and myosin II regulatory light-chain kinase
      gene expression was analysed by real-time PCR, with protein expression and
      localization analysed by Western blot and immunofluorescence. RESULTS: TNF-alpha
      increased monolayer permeability and diminished tight junction integrity. However
      both polymeric formula and infliximab completely abrogated the effects of TNF
      alpha. These monolayers displayed unchanged permeability and tight junction
      integrity compared to untreated cells (media-no-TNF-alpha controls). In contrast,
      hydrocortisone only partially abrogated the effects of TNF-alpha, with these
      monolayers having increased permeability and altered tight junction integrity
      compared to media-no-TNF-alpha controls. CONCLUSIONS: Both polymeric formula and
      infliximab completely prevent epithelial barrier dysfunction in the presence of
      TNF-alpha, whereas hydrocortisone partially prevents barrier dysfunction. These
      results provide evidence that superior mucosal healing can be achieved with both
      polymeric formula and infliximab compared to hydrocortisone.

PMID- 21953314
TI  - Development of a new immunoassay for the accurate determination of anti
      infliximab antibodies in inflammatory bowel disease.
AB  - BACKGROUND: The formation of antibodies to infliximab (ATIs) is closely
      associated with the loss of response to infliximab in patients with inflammatory
      bowel disease (IBD). We evaluated the clinical utility of a novel method to
      measure serum ATI levels in the presence of infliximab. METHODS: ATI levels were
      measured using a novel immunoassay and the conventional method in 58 patients
      with Crohn's disease (CD) under infliximab maintenance therapy. The serum
      infliximab trough levels were determined by enzyme-linked immunosorbent assay.
      RESULTS: ATIs were detected in 16 out of 58 patients (27.6%) by the new method,
      but the conventional method detected only 2 patients (3.4%) who had the two
      highest ATI titers assayed by the new method. The presence of ATIs in the samples
      positive by the new method but negative by the conventional method was confirmed
      by Western blot analysis. Western blotting analysis also indicated that the new
      method could restore the binding capacities of the ATIs whose recognition sites
      were occupied by free infliximab. In the new method, the addition of infliximab
      to the samples dose-dependently blocked the detection of ATIs. Patients positive
      for ATIs had significantly lower serum trough levels of infliximab (P < 0.01) and
      significantly higher clinical activity scores (P < 0.001) as compared with
      patients negative for ATI. CONCLUSIONS: The new method makes it possible to
      measure serum ATI levels in the presence of infliximab. This method is useful for
      deciding the optimal management strategies for IBD patients with loss of response
      to infliximab.

PMID- 21953315
TI  - In vitro evaluation of the cytotoxic and genotoxic effects of artemether, an
      antimalarial drug, in a gastric cancer cell line (PG100).
AB  - Artemisinin is a sesquiterpene lactone endoperoxide, obtained from Artemisia
      annua, and extensively used as an antimalarial drug. Many studies have reported
      the genotoxic and cytotoxic effects of artemisinins; however, there are no
      studies that compare such effects between cancer cell lines and normal human
      cells after treatment with artemether, an artemisinin derivative. Gastric cancer
      is the fourth most frequent type of cancer and the second highest cause of cancer
      mortality worldwide. Thus, the aim of this study was to evaluate the in vitro
      genotoxic and cytotoxic effects induced by artemether in gastric cancer cell line
      (PG100) and compare them with the results obtained in human lymphocytes exposed
      to the same conditions. We used MTT (3-(4,5-methylthiazol-2-yl)-2, 5-diphenyl
      tetrazolium bromide) assay, comet assay and ethidium bromide/acridine orange
      viability staining to evaluate the cytotoxic and genotoxic effects of artemether
      in PG100. MTT assay showed a decrease in the survival percentages for both cell
      types treated with different concentrations of artemether (P < 0.05). PG100 also
      showed a significant dose-dependent increase in DNA damage index at
      concentrations of 119.4 and 238.8 ug ml(-1) (P < 0.05). Our results showed that
      artemether induced necrosis in PG100 at concentrations of 238.8 and 477.6 ug ml(
      1), for all the tested harvest times (P < 0.05). In lymphocytes, artemether
      induced both apoptosis and necrosis at concentrations of 238.8 and 477.6 ug ml(
      1), for all the tested harvest times (P < 0.05). In conclusion, human lymphocytes
      were more sensitive to the cytotoxic effects of the antimalarial drug than the
      gastric cancer cell line PG100.

PMID- 21953316
TI  - Racial disparities in breast cancer mortality in a multiethnic cohort in the
      Southeast.
AB  - BACKGROUND: Although much has been done to examine those factors associated with
      higher mortality among African American women, there is a paucity of literature
      that examines disparities among rural African Americans in South Carolina. The
      purpose of this investigation was to examine the association of race and
      mortality among breast cancer patients in a large cohort residing in South
      Carolina for which treatment regimens are standardized for all patients. METHODS:
      Subjects included 1209 women diagnosed with breast cancer between 2000 and 2002
      at a large, local hospital containing a comprehensive breast center. Kaplan-Meier
      survival curves were calculated to determine survival rates among African
      American and European American women, stratified by disease stage or other
      prognostic characteristics. Adjusting for various characteristics, Cox
      multivariate survival models were used to estimate the hazard ratio (HR).
      RESULTS: The 5-year overall all-cause mortality survival proportion was ~78% for
      African American women and ~89% for European American women, P < 0.01. In
      analyses of subpopulations of women with identical disease characteristics,
      African American women had significantly higher mortality than European American
      women for the same type of breast cancer disease. In multivariate models, African
      American women had significantly higher mortality than European American women
      for both breast cancer-specific death (HR, 2.41; 95% confidence interval [CI],
      1.21-4.79) and all-cause mortality (HR, 1.42; 95% CI, 1.06-1.89). CONCLUSIONS:
      African American women residing in rural South Carolina had lower survival for
      breast cancer even after adjustment for disease-related prognostic
      characteristics. These findings support health interventions among African
      American breast cancer patients aimed at tertiary prevention strategies or
      further down-staging of disease at diagnosis.

PMID- 21953317
TI  - Peptide mapping using capillary electrophoresis offline coupled to matrix
      assisted laser desorption ionization time of flight mass spectrometry.
AB  - This article reports the results of a study carried out to evaluate the offline
      hyphenation of capillary zone electrophoresis with matrix-assisted lased
      desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) for the
      analysis of low-abundant complex samples, represented by the tryptic
      phosphorylated peptides of phosphoproteins, such as alpha-casein, beta-casein,
      and fetuin. The proposed method employs a latex-coated capillary and consists in
      the online preconcentration of the tryptic peptides by a pH-mediated stacking
      method, their separation by capillary zone electrophoresis, and subsequent
      deposition of the separated analytes onto a MALDI target for their MS analysis.
      The online preconcentration method allows loading a large sample volume (~150
      nL), which is introduced into the capillary after the hydrodynamic injection of a
      short plug of 1.0 M ammonium hydroxide solution and is sandwiched between two
      plugs of the acidic background electrolyte solution (BGE) filling the capillary.
      The sample spotting of the separated analytes onto the MALDI target is performed
      either during or postseparation using an automatic spotting device connected to
      the exit of the separation capillary. The proposed method allows the separation
      and identification of multiphosphorylated peptides from other peptides and
      enables their identification at femtomole level with improved efficiency compared
      with LC approaches hyphenated to MS.

PMID- 21953318
TI  - Hyphal morphology modification in thermal adaptation by the white-rot fungus
      Fomes sp. EUM1.
AB  - A thermotolerant white-rot fungus was identified as Fomes sp. EUM1. The strain
      exhibited maximum growth at 30  degrees C, with activation and inactivation
      energy values of 68 and 32 kJ/mol, respectively. The temperature affected the
      hyphal morphology, which was related to the thermotolerance of the microorganism:
      A shift from 30 to 40  degrees C in the growth temperature caused a decrease
      (15%) in mycelium branching; also longer (32%) and thinner (13%) hyphae were
      produced. In addition, as the temperature rose from 25 to 45  degrees C, an
      increase was observed in both the hyphal surface area (43%) and the surface
      growth rate (193%). The modification of the hyphal morphology suggests a strategy
      to colonize nutrient-rich areas while spending minimal energy for biomass
      formation under thermal stress.

PMID- 21953319
TI  - The impact of new (orphan) drug approvals on premature mortality from rare
      diseases in the United States and France, 1999-2007.
AB  - This paper investigates the impact of the introduction of new orphan drugs on
      premature mortality from rare diseases using longitudinal, disease-level data
      obtained from a number of major databases. The analysis is performed using data
      from two countries: the United States (during the period 1999-2006) and France
      (during the period 2000-2007). For both countries, we estimate models using two
      alternative definitions of premature mortality, several alternative criteria for
      inclusion in the set of rare diseases, and several values of the potential lag
      between new drug approvals and premature mortality reduction. Both the United
      States and French estimates indicate that, overall, premature mortality from rare
      diseases is unrelated to the cumulative number of drugs approved 0-2 years
      earlier but is significantly inversely related to the cumulative number of drugs
      approved 3-4 years earlier. This delay is not surprising, since most patients
      probably do not have access to a drug until several years after it has been
      launched. Although the estimates for the two countries are qualitatively similar,
      the estimated magnitudes of the US coefficients are about four times as large as
      the magnitudes of the French coefficients. This may be partly due to greater
      errors in measuring dates of drug introduction in France. Also, access to new
      drugs may be more restricted in France than it is in the United States. Our
      estimates indicate that, in the United States, potential years of life lost to
      rare diseases before age 65 (PYLL65) declined at an average annual rate of 3.3%
      and that, in the absence of lagged new drug approvals, PYLL65 would have
      increased at a rate of 0.9%. Since the US population aged 0-64 was increasing at
      the rate of 1.0% per year, this means that PYLL65 per person under 65 would have
      remained approximately constant. The reduction in the US growth rate of PYLL65
      attributable to lagged new drug approvals was 4.2%. In France, PYLL65 declined at
      an average annual rate of 1.8%. The estimates imply that, in the absence of
      lagged new drug approvals, it would have declined at a rate of 0.6%. The
      reduction in the French growth rate of PYLL65 attributable to lagged new drug
      approvals was 1.1%. Earlier access to orphan drugs could result in earlier
      reductions in premature mortality from rare diseases.

PMID- 21953320
TI  - Determinants of household direct and indirect costs: an insight for health
      seeking behaviour in Burkina Faso.
AB  - The objective of the study is to identify the determinants of household direct
      and indirect costs in the Nouna District, Burkina Faso. The data used were from a
      household survey conducted during 2000-2001. The multinominal logit models were
      applied to investigate the determinants of direct and indirect costs. The
      respondents who were sick in the rainy season and severity of illness
      significantly increased the probability of having high direct and indirect
      household costs. Acute illness occured in an adult was positively associated with
      magnitude of household indirect costs. Household economic status and utilization
      of western medical care played an important role in magnitude of direct cost. The
      information on determinants of household direct and indirect costs is necessary
      in order to get a complete picture of household costs for seeking health care and
      identification of vulnerable social groups and households.

PMID- 21953321
TI  - ASMS Directory of 2011 Members.

PMID- 21953322
TI  - High-mobility group box 1 is associated with clinicopathologic features in
      patients with hepatocellular carcinoma.
AB  - High-mobility group box 1(HMGB1) has been associated with many human cancers, but
      the role of HMGB1 in hepatocellular carcinoma (HCC) remains unclear. The aim of
      this study is to investigate the expression of HMGB1 in human HCC with regard to
      its clinical significance. Twelve cases of normal liver tissues, 34 cases of HCC
      and the corresponding liver tissue just around the tumor (LAT) were collected.
      Then, all the samples were subjected to clinicopathologic examination, reverse
      transcription-polymerase chain reaction (RT-PCR), Western-blot (WB) and
      immunohistochemical analysis for the expression of HMGB1. The relationships
      between HMGB1 mRNA expression and clinicopathologic parameters were analyzed. RT
      PCR demonstrated that the expression of relative HMGB1 mRNA (HMGB1/GAPDH) was
      0.854 +/- 0.172; the highest in the tissue of HCC, significantly up-regulated
      compared with that of 0.527 +/- 0.155 in LAT and of 0.405 +/- 0.087 in normal
      liver tissues (P < 0.001). HMGB1 mRNA overexpression was significantly associated
      with Edmondson stage, TNM stage, vascular invasion and capsule invasion. Western
      blot showed the expression of HMGB1 protein in HCC also as the highest among all
      the groups. Furthermore this overexpression revealed by immunostaining was
      predominantly localized in the nuclei of HCC; whereas, none of the stains were
      seen in normal liver cells and only a trace of it was detected in the cytoplasm
      of LAT cells. Our results suggested the overexpression of HMGB1 might be an
      important pathogenetic factor in HCC. The mechanisms of HMGB1 in HCC genesis,
      development and its possible diagnostic and prognostic roles need to be further
      explored.

PMID- 21953323
TI  - Collision metastases of breast and rectal carcinoma--a possible role for
      chemokines receptors expression.

PMID- 21953324
TI  - Relapsing tumefactive lesion in an adult with medulloblastoma previously treated
      with chemoradiotherapy and stem cell transplant.
AB  - Herein, we present an adult case of medulloblastoma who received chemotherapy,
      radiation therapy and stem cell transplantation, and underwent multiple surgical
      resections for what were thought to be recurrences; however pathology confirmed a
      diagnosis of relapsing tumefactive lesions. This phenomenon seems to be a
      consequence of stem cell transplantation rather than a simple radiation treatment
      effect.

PMID- 21953325
TI  - Anoikis: an emerging hallmark in health and diseases.
AB  - Anoikis is a programmed cell death occurring upon cell detachment from the
      correct extracellular matrix, thus disrupting integrin ligation. It is a critical
      mechanism in preventing dysplastic cell growth or attachment to an inappropriate
      matrix. Anoikis prevents detached epithelial cells from colonizing elsewhere and
      is thus essential for tissue homeostasis and development. As anchorage
      independent growth and epithelial-mesenchymal transition, two features associated
      with anoikis resistance, are crucial steps during tumour progression and
      metastatic spreading of cancer cells, anoikis deregulation has now evoked
      particular attention from the scientific community. The aim of this review is to
      analyse the molecular mechanisms governing both anoikis and anoikis resistance,
      focusing on their regulation in physiological processes, as well as in several
      diseases, including metastatic cancers, cardiovascular diseases and diabetes.

PMID- 21953326
TI  - Qualitative analysis of peer coaches' experiences with counseling African
      Americans about reducing heart disease risk.
AB  - BACKGROUND: Despite mounting evidence that peer coaches can make significant
      contributions to patient health, little is known about factors that must be
      addressed to engage and retain them in their role. OBJECTIVE: To identify
      motivators and barriers to serving as a peer coach. DESIGN: Open ended semi
      structured interviews. PARTICIPANTS AND SETTING: In a randomized trial of peer
      support, patients with well controlled hypertension and good interpersonal skills
      were recruited and trained to serve as peer coaches for African-American patients
      from the same practices who had poorly controlled hypertension. Peer coaches
      spoke by telephone at least three times with their same sex patient-clients on
      alternate months during the 6-month intervention and counseled about medication
      adherence as well as other healthy lifestyles. KEY RESULTS: Of 15 trained peer
      coaches, ten were contacted and agreed to participate in the qualitative
      interview. Peer coaches had a mean age of 66 years, 50% were women, and 80% were
      African-American. Themes regarding favorable aspects of the peer coach experience
      included: meaning and satisfaction derived from contributing to community health
      and the personal emotional and physical benefits derived from serving as a peer
      coach. Negative aspects centered on: challenges in establishing the initial
      telephone contact and wanting more information about their patient-clients'
      personal health conditions and status. Peer coaches endorsed gender matching but
      were less clear about race-matching. CONCLUSIONS: Programs that utilize peer
      support to enhance positive health behaviors should recognize that a spirit of
      volunteerism motivates many successful peer coaches. Program planners should
      acknowledge the special characteristics required of successful peer coaches when
      selecting, motivating and training individuals for this role.

PMID- 21953328
TI  - Access to care: too much or not enough?

PMID- 21953327
TI  - Mentorship, productivity, and promotion among academic hospitalists.
AB  - BACKGROUND: United States academic hospitals have rapidly adopted the hospitalist
      model of care. Academic hospitalists have taken on much of the clinical and
      teaching responsibilities at many institutions, yet little is known about their
      academic productivity and promotion. OBJECTIVE: We sought to discover the
      attitudes and attributes of academic hospitalists regarding mentorship,
      productivity, and promotion. DESIGN: We performed a web-based email survey of
      academic hospitalists consisting of 61 questions. PARTICIPANTS: Four hundred and
      twenty academic hospitalists. MAIN MEASURES: Demographic details, scholarly
      production, presence of mentorship and attitudes towards mentor, academic rank
      KEY RESULTS: Two hundred and sixty-six (63%) of hospitalists responded. The
      majority were under 41 (80%) and had been working as hospitalists for <5 years
      (62%). Only 42% of academic hospitalists had a mentor. Forty-four percent of
      hospitalists had not presented a poster or abstract at national meeting; 51% had
      not been first author on a peer-reviewed publication. Factors positively
      associated with publication of a peer-reviewed first author paper included: 1)
      male gender, AOR = 2.38 (95% CI 1.30, 4.33), 2) >20% "protected" time, AOR = 1.92
      (95% CI 1.00, 3.69), and 3) a better-than-average understanding of the criteria
      for promotion, AOR = 3.66 (95% CI 1.76, 7.62). A lack of mentorship was
      negatively associated with producing any peer-reviewed first author publications
      AOR = 0.43 (95% CI 0.23, 0.81); any non-peer reviewed publications AOR = 0.45
      (95% CI 0.24, 0.83), and leading a teaching session at a national meeting AOR =
      0.41 (95% CI 0.19, 0.88). Most hospitalists promoted to the level of associate
      professor had been first author on four to six peer-reviewed publications.
      CONCLUSIONS: Most academic hospitalists had not presented a poster at a national
      meeting, authored an academic publication, or presented grand rounds at their
      institution. Many academic hospitalists lacked mentorship and this was associated
      with a failure to produce scholarly activity. Mentorship may improve academic
      productivity among hospitalists.

PMID- 21953329
TI  - Perioperative infusion of dexmedetomidine at a high dose reduces postoperative
      analgesic requirements: a randomized control trial.
AB  - PURPOSE: We hypothesized that a high dose of dexmedetomidine (1 MUg/kg/h) could
      reduce postoperative analgesic requirements of patients. METHODS: This was a
      prospective, randomized, double-blind, placebo-controlled study carried out in
      Tohoku University Hospital. Thirty-two patients who underwent open gynecological
      abdominal surgery were randomly divided into a control (group C) and a
      dexmedetomidine group (group D). In both groups of patients, an epidural catheter
      was put in position prior to the induction of anesthesia, and continuous epidural
      infusion was started using a patient-controlled epidural analgesia (PCEA) pump.
      During the induction of anesthesia, group D patients received a loading dose of
      dexmedetomidine (1 MUg/kg over 10 min), followed by a continuous infusion at a
      rate of 1 MUg/kg/h. The patients in group C received a volume-matched infusion of
      normal saline as placebo. Consumption of PCEA bolus (local anesthetics) during
      the first postoperative 24 h, postoperative pain scores, and side effects related
      to the use of dexmedetomidine were recorded. RESULTS: Dexmedetomidine (1
      MUg/kg/h) significantly reduced PCEA bolus consumption [15.9 +/- 6.5 (group C)
      vs. 5.3 +/- 5.0 ml (group D); P = 0.0001] and postoperative pain scores. The
      infusion of dexmedetomidine produced no serious side effects, such as hemodynamic
      changes. CONCLUSIONS: Among this small patient cohort, perioperative infusion of
      dexmedetomidine (1 MUg/kg/h) resulted in antinociception without severe side
      effects. These results suggest that this method could be of interest with respect
      to improving postoperative pain status.

PMID- 21953330
TI  - High-throughput assessment of transgene copy number in sugarcane using real-time
      quantitative PCR.
AB  - Accurate and timely detection of transgene copy number in sugarcane is currently
      hampered by the requirement to use Southern blotting, needing relatively large
      amounts of genomic DNA and, therefore, the continued growth and maintenance of
      bulky plants in containment glasshouses. In addition, the sugarcane genome is
      both polyploid and aneuploid, complicating the identification of appropriate
      genes for use as references in the development of a high-throughput method. Using
      bioinformatic techniques followed by in vitro testing, two genes that appear to
      occur once per base genome of sugarcane were identified. Using these genes as
      reference genes, a high-throughput assay employing RT-qPCR was developed and
      tested using a group of sugarcane plants that contained unknown numbers of copies
      of the nptII gene encoding kanamycin resistance. Using this assay, transgene copy
      numbers from 3 to more than 50 were identified. In comparison, Southern blotting
      accurately identified the number of transgene copies for one line and by
      inference for another, but was not able to provide an accurate estimation for
      transgenic lines containing numerous copies of the nptII gene. Using the
      reference genes identified in this study, a high-throughput assay for the
      determination of transgene copy number was developed and tested for sugarcane.
      This method requires much less input DNA, can be performed much earlier in the
      production of transgenic sugarcane plants and allows much more efficient
      assessment of numerous potentially transgenic lines than Southern blotting.

PMID- 21953331
TI  - Mutations in proteasome subunit beta type 8 cause chronic atypical neutrophilic
      dermatosis with lipodystrophy and elevated temperature with evidence of genetic
      and phenotypic heterogeneity.
AB  - OBJECTIVE: Chronic atypical neutrophilic dermatosis with lipodystrophy and
      elevated temperature (CANDLE syndrome) is an autoinflammatory syndrome recently
      described in children. We undertook this study to investigate the clinical
      phenotype, genetic cause, and immune dysregulation in 9 CANDLE syndrome patients.
      METHODS: Genomic DNA from all patients was screened for mutations in PSMB8
      (proteasome subunit beta type 8). Cytokine levels were measured in sera from 3
      patients. Skin biopsy samples were evaluated by immunohistochemistry, and blood
      microarray profile and STAT-1 phosphorylation were assessed in 4 patients and 3
      patients, respectively. RESULTS: One patient was homozygous for a novel nonsense
      mutation in PSMB8 (c.405C>A), suggesting a protein truncation; 4 patients were
      homozygous and 2 were heterozygous for a previously reported missense mutation
      (c.224C>T); and 1 patient showed no mutation. None of these sequence changes was
      observed in chromosomes from 750 healthy controls. Of the 4 patients with the
      same mutation, only 2 shared the same haplotype, indicating a mutational hot
      spot. PSMB8 mutation-positive and -negative patients expressed high levels of
      interferon-gamma (IFNgamma)-inducible protein 10. Levels of monocyte chemotactic
      protein 1, interleukin-6 (IL-6), and IL-1 receptor antagonist were moderately
      elevated. Microarray profiles and monocyte STAT-1 activation suggested a unique
      IFN signaling signature, unlike in other autoinflammatory disorders. CONCLUSION:
      CANDLE syndrome is caused by mutations in PSMB8, a gene recently reported to
      cause "JMP" syndrome (joint contractures, muscle atrophy, microcytic anemia, and
      panniculitis-induced childhood-onset lipodystrophy) in adults. We extend the
      clinical and pathogenic description of this novel autoinflammatory syndrome,
      thereby expanding the clinical and genetic disease spectrum of PSMB8-associated
      disorders. IFN may be a key mediator of the inflammatory response and may present
      a therapeutic target.

PMID- 21953332
TI  - Modeling the electrophoresis of oligolysines.
AB  - CE is used to measure the electrophoretic mobility of low molecular mass oligo-L
      lysines (n=1-8) in aqueous LiH2PO4 buffer, BGE, at pH 2.5 over a range of
      temperatures (25-50  degrees C) and ionic strengths (10-100 mM). Mobilities are
      corrected for Joule heating and under the conditions of the experiment,
      interaction of the peptides with the capillary walls can be ignored. A "coarse
      grained" bead modeling methodology (BMM) (H. Pei et al., J. Chromatogr. A 2009,
      1216, 1908-1916) is used to model the mobilities. This model partially accounts
      for peptide conformation as well as the assumed form of its secondary structure.
      For highly charged oligolysines, it is necessary to properly account for the
      relaxation effect. In the present study, the BMM approach tends to overestimate
      oligolysine mobility and that effect tends to increase with increasing ionic
      strength and peptide length. It is proposed that association between the
      oligolysines and buffer components (H2PO4- in this case) that go beyond classical
      electrostatic interactions are responsible for this discrepancy. A simple binding
      model is introduced that illustrates how this association can reconcile model and
      experiment.

PMID- 21953333
TI  - Characterization of rhizobia from legumes of agronomic interest grown in semi
      arid areas of Central Spain relates genetic differences to soil properties.
AB  - A study of symbiotic bacteria from traditional agricultural legumes from Central
      Spain was performed to create a collection of rhizobia from soils differing in
      physicochemical, analytical and/or agroecological properties which could be well
      adapted to the environmental conditions of this region, and be used for
      sustainable agricultural practices. Thirty-six isolates were obtained from root
      nodules of fifteen legume species (including Cicer arietinum, Lathyrus sativus,
      Lens culinaris, Lupinus spp., Medicago sativa, Phaseolus vulgaris, Pisum sativum,
      and Vicia spp.) from three agriculture areas with soils of different pHs and from
      a forest area with undisturbed soils. Phenotypical characterization revealed
      uniformity across the thirty-six isolates, with important exceptions in terms of
      environmental tolerance (three isolates survived at high temperatures, three at
      high salinity and three at acid pH). The molecular analysis of 16S rRNA gene
      showed a close relationship of twenty-nine isolates to Rhizobium leguminosarum,
      one to Rhizobium gallicum, one to Mesorhizobium ciceri, two to Sinorhizobium
      (Ensifer) meliloti and three to Bradyrhizobium canariense. The sequence analysis
      of a symbiosis-specific gene, nod C, showed a correlation with the plant host and
      grouped twenty-six isolates with Rhizobium leguminosarum bv. viciae, establishing
      the diversity in relation to legume-host. The 16S-23S rRNA intergenic spacer
      (IGS) region allowed for intraspecific differentiation, so that strains with
      equal 16S rRNA were grouped by means of their soil origin. These results
      indicated that phenotypical and genetically related strains may be widely
      distributed in this region and that soil abiotic characteristics could have a
      substantial bearing on the selection of the strains living in each environment.

PMID- 21953334
TI  - Takayasu arteritis is characterised by disturbances of B cell homeostasis and
      responds to B cell depletion therapy with rituximab.
AB  - Introduction Takayasu arteritis (TA) is a large vessel vasculitis involving the
      aorta and its major branches. T cell-mediated autoimmunity is thought to play a
      major role in its pathogenesis, while the role of B cells is still unclear.
      METHODS: B cell subsets in the peripheral blood of 17 patients with TA were
      analysed and compared with nine patients with active systemic lupus erythematosus
      (SLE) and nine healthy controls by flow cytometry. Based on these findings, three
      patients with active refractory TA were treated with B cell depletion therapy
      (BCDT) using monoclonal anti-CD20 antibodies (rituximab). RESULTS: The absolute
      number and frequency of peripheral blood CD19(+)/CD20(-)/CD27(high) antibody
      secreting cells in patients with active TA was significantly higher than in
      healthy donors. As in active SLE, the majority of these cells are newly generated
      plasmablasts which significantly correlated with TA activity. Three patients with
      active refractory TA and expansion of plasmablasts were successfully treated with
      BCDT, which resulted in remission. CONCLUSION: Disturbances of B cell homeostasis
      may be critical in TA. Circulating plasmablasts could be a useful biomarker of
      disease activity and a tool for selecting appropriate candidates for BCDT. B
      cells and plasmablasts/plasma cells may therefore represent novel targets for
      effective therapies for TA.

PMID- 21953335
TI  - The sympathetic nervous system stimulates anti-inflammatory B cells in collagen
      type II-induced arthritis.
AB  - BACKGROUND: As previously shown, the sympathetic nervous system (SNS) shows
      proinflammatory activity during initiation of arthritis but is anti-inflammatory
      in established collagen-induced arthritis (CIA). Interleukin 10 (IL-10)-producing
      B cells suppress arthritis and are a potential target of the SNS because (1) B
      cells express functional beta(2)-adrenoceptors (beta(2)ARs) and (2) IL-10, at
      least in monocytes/macrophages, is regulated in a cAMP/PKA/CREB-dependent manner.
      OBJECTIVE: To test the hypothesis that anti-inflammatory effects of the SNS in
      CIA are mediated by stimulating IL-10-producing anti-inflammatory B cells.
      METHODS: Collagen-induced arthritis in DBA/1 mice, sympathectomy, adoptive B cell
      transfer, in vitro B cell culture, and assessment of B cell IL-10 production.
      RESULTS AND CONCLUSION: Mice treated with B cells from SNS-intact mice showed
      less severe arthritis than mice treated with B cells from sympathectomised mice.
      This anti-inflammatory action of B cells from SNS-intact mice correlated with
      increased IL-10 produced by B cells, which was mediated by norepinephrine (NE),
      in a beta(2)AR, PKA-dependent manner. However, an NE-mediated increase in IL-10
      was seen only in B cells from immunised but not naive mice, explaining in part
      the anti-inflammatory properties of the SNS in the late phase of arthritis.
      Finally, animals treated with B cells isolated from immunised mice and activated
      in vitro in the presence of a beta(2)AR stimulus showed a decrease in arthritis
      severity in comparison with controls, an approach that might be used for future
      cellular treatment strategies.

PMID- 21953336
TI  - European League Against Rheumatism recommendations for the management of
      psoriatic arthritis with pharmacological therapies.
AB  - BACKGROUND: Psoriatic arthritis (PsA) is a clinically heterogeneous disease.
      Clear consensual treatment guidance focused on the musculoskeletal manifestations
      of PsA would be advantageous. The authors present European League Against
      Rheumatism (EULAR) recommendations for the treatment of PsA with systemic or
      local (non-topical) symptomatic and disease-modifying antirheumatic drugs
      (DMARD). METHODS: The recommendations are based on evidence from systematic
      literature reviews performed for non-steroidal anti-inflammatory drugs (NSAID),
      glucocorticoids, synthetic DMARD and biological DMARD. This evidence was
      discussed, summarised and recommendations were formulated by a task force
      comprising 35 representatives, and providing levels of evidence, strength of
      recommendations and levels of agreement. RESULTS: Ten recommendations were
      developed for treatment from NSAID through synthetic DMARD to biological agents,
      accounting for articular and extra-articular manifestations of PsA. Five
      overarching principles and a research agenda were defined. CONCLUSION: These
      recommendations are intended to provide rheumatologists, patients and other
      stakeholders with a consensus on the pharmacological treatment of PsA and
      strategies to reach optimal outcomes, based on combining evidence and expert
      opinion. The research agenda informs directions within EULAR and other
      communities interested in PsA.

PMID- 21953337
TI  - Selective involvement of ERK and JNK mitogen-activated protein kinases in early
      rheumatoid arthritis (1987 ACR criteria compared to 2010 ACR/EULAR criteria): a
      prospective study aimed at identification of diagnostic and prognostic biomarkers
      as well as therapeutic targets.
AB  - OBJECTIVES: To investigate the expression and activation of mitogen-activated
      protein kinases in patients with early arthritis who are disease-modifying
      antirheumatic drug (DMARD) naive. METHODS: A total of 50 patients with early
      arthritis who were DMARD naive (disease duration <1 year) were prospectively
      followed and diagnosed at baseline and after 2 years for undifferentiated
      arthritis (UA), rheumatoid arthritis (RA) (1987 American College of Rheumatology
      (ACR) and 2010 ACR/European League Against Rheumatism (EULAR) criteria), or
      spondyloarthritis (SpA). Synovial biopsies obtained at baseline were examined for
      expression and phosphorylation of p38, extracellular signal regulated kinase
      (ERK) and c-Jun N-terminal kinase (JNK) by immunohistochemistry and digital
      analysis. Synovial tissue mRNA expression was measured by quantitative PCR
      (qPCR). RESULTS: ERK and JNK activation was enhanced at inclusion in patients
      meeting RA criteria compared to other diagnoses. JNK activation was enhanced in
      patients diagnosed as having UA at baseline who eventually fulfilled 1987 ACR RA
      criteria compared to those who remained UA, and in patients with RA fulfilling
      2010 ACR/EULAR criteria at baseline. ERK and JNK activation was enhanced in
      patients with RA developing progressive joint destruction. JNK activation in UA
      predicted 1987 ACR RA classification criteria fulfilment (R(2)=0.59, p=0.02)
      after follow-up, and disease progression in early arthritis (R(2)=0.16, p<0.05).
      Enhanced JNK activation in patients with persistent disease was associated with
      altered synovial expression of extracellular matrix components and CD44.
      CONCLUSIONS: JNK activation is elevated in RA before 1987 ACR RA classification
      criteria are met and predicts development of erosive disease in early arthritis,
      suggesting JNK may represent an attractive target in treating RA early in the
      disease process.

PMID- 21953339
TI  - Undifferentiated arthritis characteristics and outcomes when applying the 2010
      and 1987 criteria for rheumatoid arthritis.
AB  - OBJECTIVE: Undifferentiated arthritis (UA) is a diagnosis 'per exclusionem'.
      Therefore this patient population may change since the development of the
      ACR/EULAR 2010-criteria for RA. This study evaluated characteristics and outcomes
      of UA in its new shape. Second, it was evaluated whether the 2010-criteria and
      the Leiden prediction rule were congruent in categorizing UA-patients. METHODS:
      2,472 early arthritis patients were studied. RA was classified according to
      either the 1987 or the 2010-criteria. UA was defined as not fulfilling existing
      classification criteria. UA-patients were compared for baseline characteristics
      and outcomes. In 1987-UA-patients both the 2010-criteria and the Leiden
      prediction rule were applied and categorization compared. RESULTS: 2010-UA
      patients (n=776) had milder baseline characteristics than 1987-UA-patients
      (n=1,166). During follow-up, still 24% of the 2010-UA-patients fulfilled the 1987
      RA-criteria compared to 32% of the 1987-UA-patients. The 2010-UA-patients started
      less frequent DMARD-therapy and reached more frequent sustained DMARD-free
      remission. 30% of 2010-criteria-positive patients were predicted to have a low
      risk on RA; these patients achieved more frequent DMARD-free sustained remission
      than other 2010-criteria-positive patients. CONCLUSION: UA in the era of the 2010
      criteria is less prevalent and milder at presentation and in outcome. This
      implies that UA-patients with unfavorable characteristics are now more often
      classified as RA.

PMID- 21953338
TI  - Development of heart block in children of SSA/SSB-autoantibody-positive women is
      associated with maternal age and displays a season-of-birth pattern.
AB  - OBJECTIVE: Congenital heart block may develop in the fetuses of Ro/SSA-positive
      and La/SSB-positive mothers. Recurrence rates of only 10-20% despite persisting
      maternal antibodies indicate that additional factors are critical for the
      establishment of heart block. The authors investigated the influence of other
      maternal and fetal factors on heart block development in a Swedish population
      based cohort. METHODS: The influence of fetal gender, maternal age, parity and
      time of birth on heart block development was analysed in 145 families, including
      Ro/La-positive (n=190) and Ro/La-negative (n=165) pregnancies. RESULTS: There was
      a recurrence rate of 12.1% in Ro/La-positive women, and no recurrence in Ro/La
      negative women. Fetal gender and parity did not influence the development of
      heart block in either group. Maternal age in Ro/La-positive pregnancies with a
      child affected by heart block was, however, significantly higher than in
      pregnancies resulting in babies without heart block (p<0.05).Seasonal timing of
      pregnancy influenced the outcome. Gestational susceptibility weeks 18-24
      occurring during January-March correlated with a higher proportion of children
      with heart block and lower vitamin D levels during the same period in a
      representative sample of Swedish women and a corresponding higher proportion of
      children with heart block born in the summer (p<0.02). Maternal age or seasonal
      timing of pregnancy did not affect the outcome in Ro/La-negative pregnancies.
      CONCLUSION: This study identifies maternal age and seasonal timing of pregnancy
      as novel risk factors for heart block development in children of Ro/La-positive
      women. These observations may be useful for counselling when pregnancy is
      considered.

PMID- 21953340
TI  - Diagnosis of gout in patients with asymptomatic hyperuricaemia: a pilot
      ultrasound study.

PMID- 21953341
TI  - Histone deacetylase inhibitors suppress rheumatoid arthritis fibroblast-like
      synoviocyte and macrophage IL-6 production by accelerating mRNA decay.
AB  - BACKGROUND: Histone deacetylase inhibitors (HDACi) display potent therapeutic
      efficacy in animal models of arthritis and suppress inflammatory cytokine
      production in rheumatoid arthritis (RA) synovial macrophages and tissue.
      OBJECTIVES: To determine the molecular mechanisms contributing to the suppressive
      effects of HDACi on RA synovial cell activation, using interleukin 6 (IL-6)
      regulation as a model. METHODS: RA fibroblast-like synoviocytes (FLS) and healthy
      donor macrophages were treated with IL-1beta, tumour necrosis factor (TNF)alpha,
      lipopolysaccharide or polyinosinic:polycytidylic acid (poly(I:C)) in the absence
      or presence of the HDACi trichostatin A (TSA) or ITF2357 (givinostat). IL-6
      production and mRNA expression was measured by ELISA and quantitative PCR (qPCR),
      respectively. Protein acetylation and the activation of intracellular signalling
      pathways were assessed by immunoblotting. The DNA-binding activity of nuclear
      factor kappaB (NFkappaB) and activator protein 1 (AP-1) components was measured
      by ELISA-based assays. RESULTS: HDACi (0.25-1.0 MUM) suppressed RA FLS IL-6
      production induced by IL-1beta, TNFalpha and Toll-like receptor ligands.
      Phosphorylation of mitogen-activated protein kinases and inhibitor of kappaBalpha
      (IkappaBalpha) following IL-1beta stimulation were unaffected by HDACi, as were
      AP-1 composition and binding activity, and c-Jun induction. TSA induced a
      significant reduction in nuclear retention of NFkappaB in FLS 24 h after IL-1beta
      stimulation, but this did not reduce NFkappaB transcriptional activity or
      correlate temporally with reductions in IL-6 mRNA accumulation. HDACi
      significantly reduced the stability of IL-6 mRNA in FLS and macrophages.
      CONCLUSIONS: Our study identifies a novel, shared molecular mechanism by which
      HDACi can disrupt inflammatory cytokine production in RA synovial cells, namely
      the promotion of mRNA decay, and suggests that targeting HDAC activity may be
      clinically useful in suppressing inflammation in RA.

PMID- 21953342
TI  - The association between smoking and the development of psoriatic arthritis among
      psoriasis patients.
AB  - AIM: To investigate the association between smoking and psoriatic arthritis (PsA)
      among patients with psoriasis and its interaction with the HLA-C*06 allele.
      METHODS: In this exploratory case-control study, smoking status was determined at
      the time of the diagnosis of arthritis for PsA patients and at their first study
      visit for psoriasis patients, when they were confirmed not to have PsA. The
      proportions of patients exposed to smoking were compared in patients with PsA to
      those with psoriasis alone. A logistic regression model was constructed to test
      the independent association of smoking and PsA after adjusting for potential
      confounders. The statistical interaction between HLA-C*06 and smoking was tested
      through a regression model. RESULTS: The proportions of current and past smokers
      were higher in the psoriasis group compared with the PsA group (30.2% vs 23.4%
      and 26.7% vs 22.3%, p=0.001, respectively). On multivariate analysis being a
      current smoker versus a lifetime non-smoker remained inversely associated with
      PsA (OR 0.57, p=0.002), while past smoker versus lifetime non-smoker status was
      no longer significant. In a subgroup analysis, smoking remained inversely
      associated with PsA only among patients who were HLA-C*06 negative. Regression
      analysis revealed that the interaction between smoking status (ever smoked vs
      lifetime non-smoker) and HLA-C*06 was statistically significant (p=0.01).
      CONCLUSION: Smoking may be inversely associated with PsA among psoriasis
      patients. This association is not present among HLA-C*06-positive individuals.

PMID- 21953343
TI  - Disability in rheumatoid arthritis in the era of biological treatments.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is a disabling disease. The authors studied
      the impact of new, expensive and occasionally toxic biological treatments on
      disability outcomes in real-world populations of patients with RA. METHODS: The
      authors analysed Health Assessment Questionnaire Disability Index data on 4651
      adult patients with RA collected prospectively from 1983 to 2006. They studied
      trends in disability using multilevel mixed-effects multivariable linear
      regression (mixed) models that adjusted for the effects of time trends in gender,
      ethnicity, age, smoking behaviour and disease duration. RESULTS: Overall, the
      patients were predominantly female (76%), were predominantly white (88%), had 13
      years of education and have had RA for 13 years, on average. The time period from
      1983 to 2006 saw major increases in the use of disease-modifying agents and
      biological agents, and a decrease in smoking. After adjustments, the disability
      rates declined at annual rates of 1.7% (1.5-1.8%) overall and 2.7% (2.4-3.1%)
      among men. The annual rate of disability declines in the biological era was
      greater than that in the preceding period, suggesting accelerated improvement.
      These declines were documented in all patient subgroups such as men, women,
      African-Americans, obese, older age groups and early disease (p<0.001), but not
      among the 1401 patients (where disability remained stable) who died on follow-up.
      CONCLUSION: Aggressive use of traditional disease-modifying agents and
      introduction of biological agents were associated with substantial gains in
      disability outcomes. Our finding supports the prevailing notion that 'tight
      inflammation control' is a desirable therapeutic strategy.

PMID- 21953344
TI  - Subclinical renal dysfunction is independently associated with cardiovascular
      events in rheumatoid arthritis: the CARRE Study.
AB  - BACKGROUND: Patients with rheumatoid arthritis (RA) have double the risk of
      cardiovascular (CV) disease, largely independently of traditional CV risk
      factors. Renal dysfunction is associated with CV morbidity and mortality in the
      general population, but data on this association in RA are lacking. OBJECTIVE: To
      investigate the association between renal function and CV events in RA. METHODS:
      The CARRE Study is an ongoing prospective cohort study of Dutch patients with RA,
      which records CV events. Glomerular filtration rate (GFR) was estimated with the
      abbreviated Modification of Diet in Renal Disease formula. Logistic regression
      determined the association between estimated GFR and the occurrence of CV events.
      RESULTS: 353 patients were followed for 3 years, and 23 (7%) had a CV event.
      Patients who had an event had a significantly lower baseline GFR than those who
      did not (59 vs 79 ml/min, p=0.001). This association remained significant after
      adjustment for traditional risk factors: in this analysis, a decrease in GFR of 5
      ml/min was associated with a 30% (95% CI 7% to 59%) increase in the occurrence of
      CV events. During follow-up, an unfavourable change in GFR was noted in patients
      who later had a CV event compared with those who did not. CONCLUSION: These data
      confirm that, in RA, renal dysfunction is associated with a higher risk of CV
      disease independently of traditional CV risk factors.

PMID- 21953345
TI  - The anti-inflammatory effects of sympathectomy in murine antigen-induced
      arthritis are associated with a reduction of Th1 and Th17 responses.
AB  - BACKGROUND: Both facilitatory and inhibitory effects of the sympathetic nervous
      system (SNS) on experimental arthritis have been reported. It is unknown whether
      such bidirectional effects are inherent to all experimental arthritis models
      and/or whether critical time windows exist for influences of the SNS on
      inflammation. OBJECTIVES: To assess the effect of sympathectomy at different time
      points on the course and severity of murine antigen-induced arthritis (AIA).
      METHODS: AIA was induced in mice. Chemical sympathectomy with 6-hydroxydopamine
      was carried out either neonatally, in the immunisation phase, or immediately
      before AIA elicitation, or during the chronic phase. In sympathectomised and non
      sympathectomised AIA mice the inflammatory process (joint swelling,
      histopathology of inflammation and joint destruction), pain-related behaviour and
      cellular and humoral immune responses were analysed. RESULTS: Sympathectomy
      during AIA induction or neonatal sympathectomy significantly reduced the severity
      of acute AIA. Neither sympathectomy in the immunisation phase nor in the chronic
      phase influenced AIA. Flare-up reactions were reduced by sympathectomy just
      before flare-up or during the initial acute AIA stage. Sympathectomised AIA mice
      showed less hyperalgesia. Sympathectomy significantly reduced interleukin (IL) 2,
      IL-17 and transforming growth factor beta in supernatants from lymph nodes and/or
      spleen cells and antigen-specific Th1-associated IgG2a in serum; IgG1 titres were
      unaffected. The beta blocker, propranolol, and the norepinephrine reuptake
      inhibitor bupropion produced similar anti-inflammatory effects, whereas the beta
      adrenergic agonist isoproterenol increased AIA severity in neonatally
      sympathectomised mice. CONCLUSIONS: Sympathetic activity mainly increases the
      severity of acute episodes of immune-mediated arthritis. Therapeutic reduction of
      sympathetic activity at acute stages attenuates inflammation, hyperalgesia and
      proinflammatory immune parameters.

PMID- 21953347
TI  - Remission in early rheumatoid arthritis defined by 28 joint counts: limited
      consequences of residual disease activity in the forefeet on outcome.
AB  - Introduction The new American College for Rheumatology (ACR)/European League
      Against Rheumatism (EULAR) remission criteria are based on the assessment of 28
      joints. A study was undertaken to study the consequences of remission
      misclassification due to residual disease activity in the feet on physical
      function and joint damage in the subsequent year in an observational early
      disease cohort. METHODS: All patients with rheumatoid arthritis at inclusion or
      at 1-year follow-up in the early arthritis cohort of the Jan van Breemen
      Institute, The Netherlands were included. ACR/EULAR remission definitions for
      trials and clinical practice were calculated twice, once using a 28-joint count
      and once using a 38-joint count that included the 10 metatarsophalangeal joints.
      Disease stability was defined as stable x-ray scores over 1 year (change <= 0 in
      Sharp/van der Heijde scores) and stable and low scores on the Health Assessment
      Questionnaire (HAQ change <= 0 and HAQ score consistently <= 0.5), all during the
      second year after inclusion. Analyses comprised residual disease activity
      (swollen or tender joints >0) in the feet of patients who fulfilled the candidate
      remission criteria using a 28-joint count and likelihood ratios of remission
      definitions to predict disease stability. RESULTS: Of 421 patients, 9-15% reached
      remission at 1 year using a 28-joint count. Of these, 26-40% showed activity in
      the feet. Misclassification due to reduced joint counts was observed in 2-3%. A
      state of remission increased the likelihood of stability of both x-ray and HAQ,
      with similar likelihood ratios for definitions using 38-joint counts and those
      using 28-joint counts. CONCLUSION: The ability of remission definitions with 28
      joint counts versus 38-joint counts to predict long-term good radiological and
      functional outcome is similar. This confirms that inclusion of ankles and
      forefeet in the assessment of remission is not required, although inclusion of
      these joints in the examination is recommended.

PMID- 21953346
TI  - Mycophenolate mofetil but not atorvastatin attenuates atherosclerosis in lupus
      prone LDLr(-/-) mice.
AB  - RATIONALE: Recent clinical and preclinical studies have demonstrated that
      systemic lupus erythematosus (SLE) is associated with an increased risk for
      cardiovascular disease (CVD). However, unlike in the general population, little
      is known regarding the efficacy of atheroprotective interventions in patients
      with SLE. The current study aims to determine the benefit of lymphocyte
      inhibition on reducing the atherosclerotic burden in SLE-susceptible LDLr
      deficient mice. METHODS: Female LDLr(-/-) mice were lethally irradiated and
      reconstituted with bone marrow from C57Bl/6 mice (LDLr.B6) or the SLE-susceptible
      B6.Sle1.2.3 mice (LDLr.Sle). At 16 weeks post transplant, mice were treated with
      atorvastatin (10 mg/kg), mycophenolate mofetil (MMF; 40 mg/kg), or both (MMF-A)
      for 8 weeks, after which the extent of atherosclerosis and the presence of SLE
      were assessed. RESULTS: Following 8 weeks of treatment, we observed that
      atorvastatin-mediated reduction in cholesterol levels attenuated atherogenesis in
      LDLr.B6 mice but failed to significantly reduce atherosclerotic lesion size in
      LDLr.Sle mice, in spite of a significant reduction in serum cholesterol levels.
      Treatment with MMF and MMF-A attenuated atherogenesis in LDLr.B6 and LDLr.Sle
      mice. In addition, MMF-containing regimens inhibited recruitment of CD4+ T cells
      to atherosclerotic lesions in LDLr.Sle mice. In these mice, MMF also reduced the
      proportion of activated splenic T cells, as well as interleukin 10 secretion by T
      cells. With regard to lupus activity, MMF had no overt effect on anti-double
      stranded DNA (dsDNA) antibody titres or kidney function and pathology.
      CONCLUSIONS: The current study demonstrates that reduction of cholesterol levels
      alone is not atheroprotective in lupus-mediated atherogenesis. This is the first
      study to demonstrate that MMF reduces the atherosclerotic burden in a model of
      lupus-accelerated atherosclerosis. Our results suggest that MMF treatment may
      prove beneficial in preventing CVD in patients with SLE.

PMID- 21953348
TI  - Resveratrol modulates murine collagen-induced arthritis by inhibiting Th17 and B
      cell function.
AB  - BACKGROUND: Alcohol intake is inversely related to rheumatoid arthritis (RA)
      disease incidence and severity. Resveratrol, a safe, well-described plant-derived
      compound, possesses anti-inflammation and immune-regulatory properties and is
      present in red wine. As such, it could mediate anti-inflammatory properties of
      the latter and offer novel therapeutic utility in is own right. OBJECTIVE: To
      evaluate the therapeutic effect of resveratrol on collagen-induced arthritis
      (CIA) and its putative immune modulation in mice. METHODS: CIA was induced in
      DBA1 mice by immunisation with collagen II. Different doses of resveratrol were
      administered before or after the development of CIA. The levels of antibody and
      cytokines in serum or in draining lymph node (DLN) lymphocyte culture
      supernatants were measured by ELISA and Th17 cell development in DLN was
      monitored by flow cytometry. RESULTS: Either prophylactic or therapeutic
      administration of resveratrol attenuated clinical parameters and bone erosion in
      CIA mice. The arthritis-protective effects were associated with markedly reduced
      serum levels of pro-inflammatory cytokines and collagen-specific, but not total,
      IgG, and with reduced numbers of Th17 cells and the production of IL-17 in DLN.
      CONCLUSION: Resveratrol modulates inflammatory arthritis in rodents by
      selectively suppressing key cellular and humoral responses necessary for disease
      development. This may partly explain the protective effects of red wine but
      importantly may offer a novel, effective and safe pathway whereby novel agents
      could be developed to treat RA.

PMID- 21953349
TI  - Clinical manifestations of antiphospholipid syndrome (APS) with and without
      antiphospholipid antibodies (the so-called 'seronegative APS').
AB  - OBJECTIVES: Although the medical literature currently provides a growing number
      of isolated case reports of patients with clinically well-defined
      antiphospholipid syndrome (APS) and persistently negative antiphospholipid
      antibodies (aPL), there are no studies including a series of patients addressing
      the clinical features of this condition. METHODS: The authors assessed clinical
      manifestations of APS in 154 patients: 87 patients with seropositive APS and 67
      patients with thrombosis and/or pregnancy morbidity persistently negative for aPL
      and presenting with at least two additional non-criteria manifestations of APS
      (the so-called 'seronegative APS', SN-APS). Patients were interviewed at the time
      of recruitment, and a retrospective file review was carried out. RESULTS: There
      were no significant differences in the frequency of thrombotic events or
      obstetric morbidity in patients with SN-APS versus patients with seropositive
      APS: deep vein thrombosis (31.4% vs 31.0%), pulmonary embolism (23.8% vs 28.7%),
      stroke (14.9% vs 17.2%), transient ischaemic attack (11.9% vs 10.3%), early
      spontaneous abortions (67.1% vs 52.1%), stillbirths (62.5% vs 59.4%), prematurity
      (28.1% vs 21.7%) or pre-eclampsia (28.1% vs 23.1%). CONCLUSIONS: Classic and SN
      APS patients show similar clinical profiles. The results suggest that clinical
      management in patients with APS should not be based only on the presence of
      conventional aPL.

PMID- 21953350
TI  - Late-onset, eruptive syringoma in an elderly man: correlation with carbamazepine.

PMID- 21953351
TI  - Haptic processing in newborns of depressed and nondepressed mothers.
AB  - This study was conducted to compare how newborns of depressed mothers and
      newborns of nondepressed mothers gather tactile information about texture.
      Spontaneous manual activity on objects with a smooth or rough texture was
      recorded in 20 newborns born of mothers with a high risk of depression or a low
      risk of depression. An important result of the present study is that texture
      based modulation of hand-pressing frequency was observed in both neonates born of
      depressed mothers and neonates born of nondepressed mothers. Moreover, hand
      pressing frequency did not depend on the pressure exerted on the object, since
      all neonates displayed comparable pressure on the held object. Lastly, the
      results revealed that newborns of depressed mothers held the rough object twice
      as long as newborns of nondepressed mothers. These results are analyzed in
      reference to deregulated biochemical functions in neonates born of mothers with a
      high risk of depression.

PMID- 21953352
TI  - Motivated but not active: the dilemmas of incorporating interactive dance into
      gym class.
AB  - BACKGROUND: Dance Dance Revolution (DDR) is considered a tool to help children
      promote a healthy active lifestyle. Empirical studies in this field have been
      largely unexplored. The purpose of this study was to examine the relationships
      between students' mastery experiences, situational motivation, and physical
      activity levels in DDR. METHODS: One hundred and ninety-five seventh, eighth, and
      ninth graders participated in a 2-week DDR unit. Students' physical activity
      levels and situational motivation [intrinsic motivation (IM), identified
      regulation (IR), external regulation, and amotivation) were measured for 3
      classes. RESULTS: Students were motivated to play DDR, but their moderate-to
      vigorous physical activity (MVPA) was low (ie, mean=4.95%). In addition, students
      with successful mastery experiences had significantly higher IM, IR, and MVPA.
      CONCLUSIONS: Although students were motivated for DDR, they were not physically
      active in DDR. In addition, successful mastery experience played an important
      role in students' motivation and physical activity levels in DDR.

PMID- 21953353
TI  - How is retrospective independent review influenced by investigator-introduced
      informative censoring: a quantitative approach.
AB  - A reliable determination of progression is of key importance in determining
      progression-free survival in oncology trials. An independent review of tumour
      assessments made by investigators is often implemented with the aim of reducing a
      possible bias. Often, the independent review is performed in a prespecified but
      retrospective fashion by reviewing a patient after all assessments have been
      performed. It has been discussed that this mechanism can lead to informative
      censoring with respect to independent review. This is caused by the fact that
      often no further assessments are available after the investigator has declared
      the patient to be progressive, possibly leading to a considerable amount of
      patients being judged progressive by the investigator and being censored by
      independent review. We introduce and investigate a model for the error in
      assessment with the aim of quantifying the bias in independent review. The model
      is based on single error probabilities at each assessment time-point that are
      independent from each other but dependent on the time to the true progression
      time-point. The bias introduced for the independent review is described and
      quantified. We show that the investigator assessments of progression can lead to
      less bias for progression-free survival than the results for independent review.
      Results show that a within-arm discordance rate is not necessarily correlated
      with the bias in independent review. Finally, we propose an approach for a
      sensitivity analysis that is a useful tool to sandwich the true underlying
      distribution by the results for independent review itself and the described
      sensitivity analysis.

PMID- 21953354
TI  - Ascorbic acid mitigates the myocardial injury after cardiac arrest and electrical
      shock.
AB  - PURPOSE: To examine the effects of ascorbic acid (AA) administrated during
      cardiopulmonary resuscitation (CPR) on the myocardial injury in a rat model of
      ventricular fibrillation (VF) and electrical shock (ES). METHODS: VF was induced
      in male Wistar rats and left untreated for 5 min, followed by 1 min of CPR, and
      then one ES of 5 J. At the start of CPR, animals received either intravenous
      administration of AA (100 mg/kg) or Tempol (30 mg/kg), two antioxidants, or 0.9%
      saline (VF + ES group). After ES, animals were immediately killed. Myocardial
      lipoxidation was determined by malondialdehyde (MDA) assay. The histology and
      ultrastructural changes of myocardium were also evaluated. The mitochondrial
      permeability transition pore (mPTP) opening was measured based on the
      mitochondrial swelling rate. The complex activities and respiration of
      mitochondria were assessed, too. RESULTS: Increased myocardial injury and
      mitochondrial damage in the VF + ES group were noted. AA and Tempol alleviated
      such damages. Both AA and Tempol improved accelerated mitochondrial swelling;
      decreased complex activities and respiratory dysfunction occurred in the VF + ES
      group. The animals receiving AA and Tempol during CPR had better successful
      resuscitation rates and 72-h survival than the VF + ES group. CONCLUSIONS:
      Intravenous administration of AA and Tempol at the start of CPR may reduce lipid
      peroxidation and myocardial necrosis, diminish mitochondrial damage, facilitate
      resuscitation, and improve outcomes after VF + ES.

PMID- 21953355
TI  - A software framework for analysing solid-state MAS NMR data.
AB  - Solid-state magic-angle-spinning (MAS) NMR of proteins has undergone many rapid
      methodological developments in recent years, enabling detailed studies of protein
      structure, function and dynamics. Software development, however, has not kept
      pace with these advances and data analysis is mostly performed using tools
      developed for solution NMR which do not directly address solid-state specific
      issues. Here we present additions to the CcpNmr Analysis software package which
      enable easier identification of spinning side bands, straightforward analysis of
      double quantum spectra, automatic consideration of non-uniform labelling schemes,
      as well as extension of other existing features to the needs of solid-state MAS
      data. To underpin this, we have updated and extended the CCPN data model and
      experiment descriptions to include transfer types and nomenclature appropriate
      for solid-state NMR experiments, as well as a set of experiment prototypes
      covering the experiments commonly employed by solid-sate MAS protein NMR
      spectroscopists. This work not only improves solid-state MAS NMR data analysis
      but provides a platform for anyone who uses the CCPN data model for programming,
      data transfer, or data archival involving solid-state MAS NMR data.

PMID- 21953356
TI  - [Subtypes of patients with fibromyalgia, psychopathological characteristics and
      quality of life].
AB  - INTRODUCTION. The main goal of this work was to identify subgroups of patients
      with fibromyalgia (FM) by means of a frequently used clinical tool, the
      Fibromyalgia Impact Questionnaire (FIQ). METHODOLOGY. A total of 66 women
      diagnosed with FM participated in the study. Two subgroups of patients were
      identified by analysis of a hierarchical cluster of selected items from the FIQ
      (pain, fatigue, morning tiredness, stiffness, anxiety and depressive symptoms).
      RESULTS. The type I FM-group had very high levels of fatigue, morning tiredness
      and anxiety, and high levels of joint stiffness, pain and depressive symptoms,
      while the type II FM-group had predominantly moderate levels of fatigue and
      morning tiredness, with moderate low levels of pain and stiffness along with a
      low level of depression and anxiety. CONCLUSIONS. Type I FM-group also had lower
      healthrelated quality of life, especially through emotional reactions and social
      isolation as well as more psychopathological affections than presented by type II
      FM-group.

PMID- 21953357
TI  - [Outcomes of a suicide prevention program in the general population; Barcelona
      Dreta de L Eixample district].
AB  - BACKGROUND AND OBJECTIVE. Suicide and self-destructive behaviors are not only
      health problems but are also related to social and personal aspects. Public
      health and community action can play an important role in increasing survival
      among those at risk. We present the results of a program based on health
      education among the general population and in a specific health care setting to
      monitor the at risk population. SUBJECTS AND METHOD. The Suicide Behavior
      Prevention Program (SBPP) developed in the Dreta de l'Eixample district in
      Barcelona city included 219 patients, 148 (67.5%) of whom completed a 12-month
      follow-up. We selected a comparison group from a neighboring district that did
      not have a SBPP. This group was made up of 180 patients, 167 of whom completed
      the 12-month follow-up. RESULTS. Main differences between the two groups were
      that patients who were enrolled in the SBPP consulted more often for suicidal
      thoughts than those in the comparative group (36% vs 25%), had fewer hospital
      admissions (6% vs 36%), presented fewer repeated suicide attempts over the 12-
      month follow-up (11% vs 32%) and showed longer time to repeat attempt.
      CONCLUSIONS. Early detection of suicidal ideation and adherence to post-suicide
      attempt treatment reduce the risk of recurrent suicide attempts. Further studies
      with longer follow up may help to reduce suicide mortality. Key words (MEDLINE
      MeSH): Suicide, "Suicide, attempted", Risk reduction behavior, Health education,
      Follow-up studies, "Outcome assessment (Health care)"

PMID- 21953358
TI  - [Do depressed patients comply with treatments prescribed?: a cross-sectional
      study of adherence to the antidepressant treatment].
AB  - INTRODUCTION. Compliance with antidepressant treatment is a very relevant factor
      in the outcome of depressive disorders. Poor compliance has been associated with
      worse outcome, increased rate of relapses and greater cost. This study has aimed
      to describe adherence to antidepressant treatment in a sample of primary care
      patients with a diagnosis of depression in 2007. METHODS. Randomized sampling was
      made of patients with depression and antidepressant treatment attended in two
      primary care teams. Their medical records were reviewed to obtain the total
      number of prescriptions given to patients and the total number of prescriptions
      dispensed in the pharmacies. The difference between prescriptions written and
      collected was calculated. A difference of +/- 2 was considered as good
      compliance. Results are shown as percentages. Comparisons were made with the chi
      square, Student's T and ANOVA tests, where appropriate. RESULTS. The simple was
      made up of 212 patients. Mean age was 63.2 years (SD 15.27). In the sample, 66.5%
      were treated with only one antidepressant and 24.1% with two. The percentage of
      non-compliance was 33.96% (95% CI: 25.35-40.57). Treatment-adherent patients have
      a lower percentage of long-term treatment with other drugs. The percentage of
      treatment-adherent women was higher than non-adherent (p=0.015). No differences
      were found in compliance among patients treated in the mental health center.
      CONCLUSIONS. One third of patients on antidepressant drug treatment were non
      compliers because the drugs were not picked up properly from the pharmacies. We
      need to develop strategies to improve the therapeutic adherence of patients.

PMID- 21953359
TI  - [Research contributions of Spanish Psychiatry (2004-2009): a bibliometric
      analysis of a university department].
AB  - Psychiatric research in Spain went through a notorious increase in quality and
      quantity of peer-reviewed papers during the last decade of the previous century,
      in parallel with other medical disciplines. Although there have been systematic
      studies of scientific production, they are inadequate from the perspective of the
      research groups and particularly from university departments. We considered this
      bibliometric study, in order to analyze the scientific production of the
      Department of Psychiatry and Forensic Medicine, at the Autonomous University of
      Barcelona, UAB [DPsML]. METHODOLOGY. In a cross-sectional survey of independent
      groups (n = 57, 54% men), indicators were applied to production, quality,
      visibility/distribution and sustained popularity. RESULTS. DPsML research groups,
      published 314 articles and/or reviews (216 international) between 2004 - 2009,
      reaching a total of 974 quotations in the period (16 quots./ basic researcher and
      11.3 quots./clinical researcher). Contributions at the Thomson Scientific Index
      [TSI], come from clinical groups (56.48%), and basic groups: 43.52%. The basic
      groups showed on average impact factor of 5.12 and clinical groups of 2.
      CONCLUSIONS. DPsML published 11.84% of most cited papers in Spanish psychiatry,
      20% in the field of drug addiction and 20.84% in the field of behavioral
      science,1 the inconsistent results with other bibliometric studies2 on the same
      researchers, shows the need for more tight and demanding indicators and mapping
      of production encompassing, both research groups as molar units (university
      departments). Key words: Bibliometrics, Scientific output, Impact index, Citation
      analysis, Psychiatry.

PMID- 21953360
TI  - [Typus melancholicus from tellenbach up to the present day: a review about the
      premorbid personality vulnerable to melancholia].
AB  - The concept of Typus Melancholicus (TM) was shaped by Tellenbach to describe the
      premorbid and intermorbid personality vulnerable to endogenous depression. The
      first part of this paper aims to point out the basic principles of Tellenbach's
      theory - the method, the concept of endon, of rhythmic, of situation, of
      rimanence, of includence and of despair. Then, we present a systematic
      description of the premorbid personality features - orderliness,
      conscientiousness, hyper/hetereonomia and intolerance of ambiguity. Furthermore,
      we present two clinical cases, one from Tellenbach and the other from our
      clinical practice to underline the typical way which links the premorbid
      condition to melancholia. Also, we propose a review of the scientific literature
      from Tellenbach's work to the present day. Finally, we discuss the clinical
      importance of the TM construct.

PMID- 21953361
TI  - [Therapeutic and pharmacologic differences between medications used in the
      treatment of bipolar disorders: seven-year update].
AB  - A detailed review was published in 2004 on the therapeutic properties of the
      medications used in the treatment of bipolar disorders (Tamayo, JM et al. Actas
      Esp Psiquiatr 2004;32(Supl. 1):3-17). At the time it could be concluded that
      although mood stabilizers (euthymics) share some action mechanisms, they are also
      significantly different from each other with respect to their therapeutic
      properties in the various phases of bipolar disorders. This led to a proposed
      change in their generic classification as "mood stabilizers" to a new
      classification that includes: antimanic medications, partial mood stabilizers,
      and euthymics. Since then, several randomized, double-blind studies and meta
      analyses that explore the effectiveness and tolerability of these medications
      have been published. This updated review aims to assess the validity of the
      proposed classification in the light of new evidence.

PMID- 21953362
TI  - [Psychological study of the dysthymic disorder in the woman].
AB  - In this article, we study two dysthymic women who we are treating with
      psychotherapy in order to reveal the inner components that maintain depressive
      symptoms. The same findings have been confirmed in other dysthymic patients. The
      result of the study consisted in discovering a sentimental separation from their
      love object, while the woman still lives with her partner and while the
      depressive symptoms are appearing insidiously. This development leads them to the
      deterioration in the "ideal of love" they sought, that supported their lives and
      served as an "anchor of their personality. This point of view places classic
      notion about mourning into doubt.

PMID- 21953363
TI  - Effect of raloxifene (a Selective Estrogen Receptor Modulator (SERM)) as
      coadjuvant to antidepressant treatment: a case report.
AB  - We report a case of a woman with a depressive disorder with partial response to
      antidepressant treatment. Raloxifene, a Selective Estrogen Receptor Modulator
      (SERM) was added to the treatment, the patient achieving complete remission of
      her depressive symptoms. The interest of our case lies in the fact that it
      exemplifies the relationship between depressive disorders and hormonal changes
      during menopause. Furthermore, raloxifene may become a novel therapeutic option
      in some postmenopausal women who do not respond or only partially respond to
      SSRIs, especially in those with a history of depressive disorders related to
      menopause.

PMID- 21953364
TI  - [Switching to quetiapine fumarate monotherapy for treatment-resistant
      schizophrenia: a report of five cases].
AB  - We assessed the efficacy and tolerance of switching to monotherapy with
      quetiapine fumarate (QF) in treatmentresistant schizophrenia with other
      antipsychotics, including atypical ones. QF treatment was maintained for 8 weeks.
      The PANSS scores improved at least 40% over this period. QF was well tolerated
      without the presence of serious adverse effects. Switching to QF in these
      patients may therefore be considered as optimal in response and tolerance. Key
      words: Schizophrenia, Treatment-resistant, Antipsychotics, Quetiapine fumarate.

PMID- 21953365
TI  - Production of polyhydroxyalkanoates by Burkholderia cepacia ATCC 17759 using a
      detoxified sugar maple hemicellulosic hydrolysate.
AB  - Sugar maple hemicellulosic hydrolysate containing 71.9 g/l of xylose was used as
      an inexpensive feedstock to produce polyhydroxyalkanoates (PHAs) by Burkholderia
      cepacia ATCC 17759. Several inhibitory compounds present in wood hydrolysate were
      analyzed for effects on cell growth and PHA production with strong inhibition
      observed at concentrations of 1 g/l furfural, 2 g/l vanillin, 7 g/l levulinic
      acid, and 1 M acetic acid. Gradual catabolism of lower concentrations of these
      inhibitors was observed in this study. To increase the fermentability of wood
      hydrolysate, several detoxification methods were tested. Overliming combined with
      low-temperature sterilization resulted in the highest removal of total inhibitory
      phenolics (65%). A fed-batch fermentation exhibited maximum PHA production after
      96 h (8.72 g PHA/L broth and 51.4% of dry cell weight). Compositional analysis by
      NMR and physical-chemical characterization showed that PHA produced from wood
      hydrolysate was composed of polyhydroxybutyrate (PHB) with a molecular mass (M
      (N)) of 450.8 kDa, a melting temperature (T (m)) of 174.4 degrees C, a glass
      transition temperature (T (g)) of 7.31 degrees C, and a decomposition temperature
      (T (decomp)) of 268.6 degrees C.

PMID- 21953367
TI  - Encapsulation of thyme (Thymus serpyllum L.) aqueous extract in calcium alginate
      beads.
AB  - BACKGROUND: Encapsulation of Thymus serpyllum L. aqueous extract within calcium
      alginate beads was studied in order to produce dosage formulations containing
      polyphenolic compounds. Electrostatic extrusion was applied for encapsulation of
      thyme aqueous extract in alginate gel beads. In addition to hydrogel beads, heat
      dried and freeze-dried forms of beads were examined. METHODS: Encapsulation
      systems were examined and compared in order to choose the optimal one with
      respect to entrapment efficiency, preservation of antioxidant activity and
      thermal behaviour under heating conditions simulating the usual food processing.
      RESULTS: The beads obtained with approximately 2 mg g-1 of gallic acid
      equivalents encapsulated in 0.015 g mL-1 of alginate were spheres of a uniform
      size of about 730 um. Encapsulation efficiency varied in the range 50-80%
      depending on the encapsulation method. Besides, the analysis reveals that the
      encapsulation process and the material used did not degrade the bioactive
      compounds, as the total antioxidant content remained unchanged. This was verified
      by Fourier transform infrared analysis, which proved the absence of chemical
      interactions between extracted compounds and alginate. Addition of a filler
      substance, such as sucrose and inulin, in the dried product reduced its collapse
      and roundness distortion during drying process. CONCLUSION: This study
      demonstrates the potential of using hydrogel material for encapsulation of plant
      poplyphenols to improve their functionality and stability in food products.

PMID- 21953366
TI  - Induction of osteoarthritis and metabolic inflammation by a very high-fat diet in
      mice: effects of short-term exercise.
AB  - OBJECTIVE: To test the hypotheses that obesity due to a very high-fat diet
      induces knee osteoarthritis (OA), and that short-term wheel-running exercise
      protects against obesity-induced knee OA by reducing systemic inflammation and
      metabolic dysregulation. METHODS: Male C57BL/6J mice were fed either a control
      diet (13.5% kcal from fat) or a very high-fat diet (60% kcal from fat) from age
      12 weeks to age 24 weeks. From 20 to 24 weeks of age, half of the mice were
      housed with running wheels. The severity of knee OA was determined by assessing
      histopathologic features, and serum cytokines were measured using a multiplex
      bead immunoassay and enzyme-linked immunosorbent assays. Body composition was
      quantified by dual-energy x-ray absorptiometry, and insulin resistance was
      assessed by glucose tolerance testing. RESULTS: Feeding mice with a very high-fat
      diet increased knee OA scores and levels of serum leptin, adiponectin, KC (mouse
      analog of interleukin-8 [IL-8]), monokine induced by interferon-gamma (CXCL9),
      and IL-1 receptor antagonist to an extent in proportion to the gain in body fat
      (3-fold increase in percent body fat compared to controls). Wheel-running
      exercise reduced progression of OA in the medial femur of obese mice. In
      addition, exercise disrupted the clustering of cytokine expression and improved
      glucose tolerance, without reducing body fat or cytokine levels. CONCLUSION:
      Obesity induced by a very high-fat diet in mice causes OA and systemic
      inflammation in proportion to body fat. Increased joint loading is not sufficient
      to explain the increased incidence of knee OA with obesity, as wheel running is
      protective rather than damaging. Exercise improves glucose tolerance and disrupts
      the coexpression of proinflammatory cytokines, suggesting that increased aerobic
      exercise may act independently of weight loss in promoting joint health.

PMID- 21953368
TI  - Sonographic detection of transient gas in the portal vein in an infant following
      abdominal surgery: a possible sign of adhesive small bowel obstruction.
AB  - We present a case of sonographically detected transient gas in the portal vein in
      a 4.5-month-old infant who had a history of two consecutive jejunectomies due to
      jejunal stenoses and was admitted to our hospital with clinical and laboratory
      findings consistent with a subacute small bowel obstruction and dehydration.
      Sonography excluded other pathologies and the patient was treated conservatively
      with success. The presence of gas in the portal vein could be a sign of an
      underlying mechanical obstacle, as another episode of small bowel obstruction 1
      month later required surgical treatment of adhesive intestinal obstruction.

PMID- 21953369
TI  - Patients with minimal hepatic encephalopathy show impaired mismatch negativity
      correlating with reduced performance in attention tests.
AB  - Attention deficit is an early event in the cognitive impairment of patients with
      minimal hepatic encephalopathy (MHE). The underlying mechanisms remain unclear.
      Mismatch negativity (MMN) is an auditory event-related potential that reflects an
      attentional trigger. Patients with schizophrenia show impaired attention and
      cognitive function, which are reflected in altered MMN. We hypothesized that
      patients with MHE, similarly to those with schizophrenia, should show MMN
      alterations related with attention deficits. The aims of this work were to assess
      whether (1) MMN is altered in cirrhotic patients with MHE, compared to those
      without MHE, (2) MMN changes in parallel with performance in attention tests
      and/or MHE in a longitudinal study, and (3) MMN predicts performance in attention
      tests and/or in the Psychometric Hepatic Encephalopathy Score (PHES). We
      performed MMN analysis as well as attention and coordination tests in 34 control
      subjects and in 37 patients with liver cirrhosis without MHE and 23 with MHE.
      Patients with MHE show reduced performance in selective and sustained attention
      tests and in visuomotor and bimanual coordination tests. The MMN wave area was
      reduced in patients with MHE, but not in those without MHE. In the longitudinal
      study, MMN area improved in parallel with performance in attention tests and PHES
      in 4 patients and worsened in parallel in another 4. Logistic regression analyses
      showed that MMN area predicts performance in attention tests and in PHES, but not
      in other tests or critical flicker frequency. Receiver operating characteristic
      curve analyses showed that MMN area predicts attention deficits in the number
      connection tests A and B, Stroop tasks, and MHE, with sensitivities of 75%-90%
      and specificities of 76%-83%. CONCLUSION: MMN area is useful to diagnose
      attention deficits and MHE in patients with liver cirrhosis.

PMID- 21953371
TI  - Vascular response to zotarolimus-coated balloons in injured superficial femoral
      arteries of the familial hypercholesterolemic Swine.
AB  - BACKGROUND: Drug-coated balloons are rapidly emerging as a therapeutic
      alternative for the interventional treatment of peripheral vascular disease. The
      purpose of this study was to test the hypothesis that an angioplasty balloon
      coated with the mTOR inhibitor zotarolimus (ZCB) would inhibit neointimal
      hyperplasia in a novel injury-based superficial femoral artery model in the
      familial hypercholesterolemic swine. METHODS AND RESULTS: A total of 44 familial
      hypercholesterolemic swine were included (12 designated to study tissue
      pharmacokinetics and 32 to study safety and efficacy). Fogarty balloon denudation
      was performed in all superficial femoral artery segments, followed by balloon
      angioplasty. In the pharmacokinetic study, a total of 24 ZCBs (300 MUg/cm(2))
      were used. Zotarolimus was detected in arterial tissue at 5 minutes (162 ng/mg of
      tissue), 24 hours (5.9 ng/mg of tissue), and 28 days (0.007 ng/mg of tissue)
      after ZCB inflation. In the safety and efficacy study, superficial femoral artery
      segments were randomized to either high-dose (600 MUg/cm(2), n=16), low-dose (300
      MUg/cm(2), n=16), or paired uncoated balloons (high-dose ZCB control, n=16; low
      dose ZCB control, n=16). At 28 days, the percentage of angiographic stenosis was
      similar among all tested groups. Histological analysis demonstrated a reduction
      in neointimal formation in both ZCB groups compared with controls (high-dose ZCB
      44% reduction, P=0.007; low-dose ZCB 22% reduction, P=0.08). There was no
      evidence of delayed arterial healing or vascular toxicity in any of the ZCB
      groups. CONCLUSIONS: The single delivery of zotarolimus via coated balloon is
      feasible, and therapeutic levels are maintained up to 28 days. The ZCB technology
      appears to be effective in the reduction of neointimal proliferation in the
      superficial femoral artery of the familial hypercholesterolemic swine.

PMID- 21953370
TI  - Paclitaxel-eluting stents show superiority to balloon angioplasty and bare metal
      stents in femoropopliteal disease: twelve-month Zilver PTX randomized study
      results.
AB  - BACKGROUND: Sustained benefits of drug-eluting stents in femoropopliteal arteries
      have not been demonstrated. This prospective, multinational, randomized study was
      designed to compare the 12-month safety and effectiveness of a polymer-free,
      paclitaxel-coated nitinol drug-eluting stent (DES) with percutaneous transluminal
      angioplasty (PTA) and provisional bare metal stent (BMS) placement in patients
      with femoropopliteal peripheral artery disease. METHODS AND RESULTS: Patients
      were randomly assigned to primary DES implantation (n=236) or PTA (n=238).
      Demographics and lesion characteristics were similar between groups (eg, average
      lesion length, approximately 65+/-40 mm). One hundred twenty patients had acute
      PTA failure and underwent secondary random assignment to provisional DES (n=61)
      or BMS (n=59). Primary end points were the 12-month rates of event-free survival
      and patency in the primary DES and PTA groups. Compared with the PTA group, the
      primary DES group exhibited superior 12-month event-free survival (90.4% versus
      82.6%; P=0.004) and primary patency (83.1% versus 32.8%; P<0.001), satisfying the
      primary hypotheses. In the secondary evaluations, (1) the primary DES group
      exhibited superior clinical benefit compared with the PTA group (88.3% versus
      75.8%; P<0.001), (2) the provisional DES group exhibited superior primary patency
      (89.9% versus 73.0%; P=0.01) and superior clinical benefit (90.5% and 72.3%,
      P=0.009) compared with the provisional BMS group, and (3) the stent fracture rate
      (both DES and BMS) was 0.9% (4/457). CONCLUSIONS: Femoropopliteal peripheral
      artery disease treatment with the paclitaxel-eluting stent was associated with
      superior 12-month outcomes compared with PTA and provisional BMS placement.

PMID- 21953372
TI  - Ranolazine injection into coronary or femoral arteries exerts marked, transient
      regional vasodilation without systemic hypotension in an intact porcine model.
AB  - BACKGROUND: We examined whether intracoronary or intrafemoral administration of
      ranolazine produces local vasodilation. METHODS AND RESULTS: Effects of intra
      arterial ranolazine on coronary and femoral artery vasodilation and systemic
      hemodynamic function were studied in anesthetized pigs (n=27). Ranolazine,
      nitroglycerin, or saline (control) was injected into the left anterior descending
      (LAD) coronary artery or femoral artery (2-mL bolus in 10 seconds). Pretreatment
      with prazosin (300 MUg/kg IV) allowed determination of alpha(1)-adrenergic
      receptor involvement (n=8). Rapid intracoronary administration of ranolazine
      (0.048 mg/kg) to achieve high local concentrations resulted in 91+/-11% increase
      in LAD coronary artery flow and 39+/-7% reduction in coronary vascular resistance
      (both, P<0.0001). This effect lasted 2-3 minutes without change in heart rate or
      rate-pressure product. Mean arterial pressure decreased marginally (by 2+/-1 mm
      Hg, P=0.01). Maximum systemic plasma concentration (0.93+/-0.29 MUmol/L) remained
      in subtherapeutic range. Pretreatment with prazosin abolished these effects.
      Intracoronary nitroglycerin (100 MUg) increased LAD coronary artery flow by 112+/
      25% (P=0.02), but the effect lasted <2 minutes; mean arterial pressure decreased
      by 4+/-1 mm Hg (P=0.01). Intrafemoral injection of ranolazine (0.24 mg/kg, ie,
      one-tenth of the systemic bolus) resulted in a 70+/-19% increase in femoral
      artery flow (P=0.05) and 26+/-5% reduction in femoral artery resistance
      (P=0.004). At 2 minutes after the injection, the femoral flow remained 16+/-9%
      above the baseline and dilatory effects occurred without tolerance to repeated
      injections. CONCLUSIONS: Intracoronary or intrafemoral ranolazine bolus exerts a
      marked, 2- to 3-minute dilatory effect that is comparable to nitroglycerin in
      magnitude but more persistent, attributable primarily to alpha(1)-adrenergic
      blockade.

PMID- 21953373
TI  - Transarterial Medtronic CoreValve system implantation for degenerated surgically
      implanted aortic prostheses.
AB  - BACKGROUND: To assess the results of transcatheter aortic valve implantation
      (TAVI) using the Medtronic CoreValve System (MCS), through the transarterial
      approach, in high-risk patients with degenerated surgically implanted aortic
      bioprostheses (SP). METHODS AND RESULTS: Of 241 patients who underwent TAVI, 10
      (4%) had a degenerated SP. The approach was percutaneous transfemoral in 9 cases
      and surgical transaxillary in 1. Patients were age 75+/-10 years of age. All were
      in New York Heart Association classes III or IV and at high risk for repeated
      surgery. Seven patients had stented, 2 stentless, and 1 homograft SP. The failure
      mode was predominant regurgitation in 7 cases and stenosis (aortic valve area,
      0.7+/-0.2 cm(2); mean gradient, 58+/-16 mm Hg) in 3. Based on the echographic
      measurements, 8 patients received a 26-mm, and 2 a 29-mm-diameter MCS. Procedural
      success rate was 100%. There was 1 in-hospital death, 1 stroke with moderate
      sequelae, and 1 pacemaker implantation. There were no other adverse events at 30
      days. The mean postimplantation transprosthetic gradient was 13+/-7 mm Hg;
      periprosthetic regurgitation was absent or trivial in 9 cases and grade 2 in 1.
      After a median follow-up of 5 months, there were no additional adverse events.
      All but 1 of the hospital survivors were in New York Heart Association classes I
      or II. CONCLUSIONS: These results suggest that transarterial MCS implantation in
      degenerated SP is feasible and may lead to hemodynamic and clinical improvement
      in patients who are poor candidates for repeated surgery, pending confirmation in
      larger series with longer follow-up.

PMID- 21953374
TI  - Critical evaluation of the use of cell cultures for inclusion in clinical trials
      of patients affected by collagen VI myopathies.
AB  - Collagen VI myopathies (Ullrich congenital muscular dystrophy (UCMD), Bethlem
      myopathy (BM), and myosclerosis myopathy) share a common pathogenesis, that is,
      mitochondrial dysfunction due to deregulation of the permeability transition pore
      (PTP). This effect was first identified in the Col6a1(-/-) mouse model and then
      in muscle cell cultures from UCMD and BM patients; the normalizing effect of
      cyclosporin A (CsA) confirmed the pathogenic role of PTP opening. In order to
      determine whether mitochondrial performance can be used as a criterion for
      inclusion in clinical trials and as an outcome measure of the patient response to
      therapy, it is mandatory to establish whether mitochondrial dysfunction is
      conserved in primary cell cultures from UCMD and BM patients. In this study we
      report evidence that mitochondrial dysfunction and the consequent increase of
      apoptotic rate can be detected not only, as previously reported, in muscle, but
      also in fibroblast cell cultures established from muscle biopsies of collagen VI
      related myopathic patients. However, the mitochondrial phenotype is no longer
      maintained after nine passages in culture. These data demonstrate that the dire
      consequences of mitochondrial dysfunction are not limited to myogenic cells, and
      that this parameter can be used as a suitable diagnostic criterion, provided that
      the cell culture conditions are carefully established.

PMID- 21953375
TI  - Investigation into the biological properties of the olive polyphenol,
      hydroxytyrosol: mechanistic insights by genome-wide mRNA-Seq analysis.
AB  - The medicinal properties of the leaves and fruit of Olea Europaea (olive tree)
      have been known since antiquity. Numerous contemporary studies have linked the
      Mediterranean diet with increased health. In particular, consumption of olive oil
      has been associated with a decreased risk of cardiovascular disease and certain
      cancers. Increasingly, there has been an interest in the biological properties of
      polyphenols, which are minor constituents of olive oil. For example,
      hydroxytyrosol has been shown to be a potent antioxidant and has anti-atherogenic
      and anti-cancer properties. The overall aim of this study was to provide insights
      into the molecular mechanisms of action of hydroxytyrosol using genome-wide mRNA
      Seq. Initial experiments were aimed at assessing cytotoxicity, apoptosis and cell
      cycle effects of hydroxytyrosol in various cell lines. The findings indicated a
      dose-dependent reduction in cell viability in human erythroleukemic K562 and
      human keratinocytes. When comparing the viability in parental CEM-CCRF and R100
      cells (which overexpress the P-glycoprotein pump), it was determined that the
      R100 cells were more resistant to effects of hydroxytyrosol suggesting efflux by
      the multi-drug resistance pump. By comparing the uptake of Hoechst 33342 in the
      two cell lines that had been pretreated with hydroxytyrosol, it was determined
      that the polyphenol may have P-glycoprotein-modulating activity. Further, initial
      studies indicated modest radioprotective effects of relatively low doses of
      hydroxytyrosol in human keratinocytes. Analysis of mRNA sequencing data
      identified that treatment of keratinocytes with 20 MUM hydroxytyrosol results in
      the upregulation of numerous antioxidant proteins and enzymes, including heme
      oxygenase-1 (15.46-fold upregulation), glutaredoxin (1.65) and glutathione
      peroxidase (1.53). This may account for the radioprotective activity of the
      compound, and reduction in oxidative stress suggests a mechanism for
      chemoprevention of cancer by hydroxytyrosol. Alteration in the expression of
      transcription factors may also contribute to the anti-cancer effects described in
      numerous studies. These include changes in the expression of STAT3, STAT6, SMAD7
      and ETS-1. The telomerase subunit TERT was also found to be downregulated in K562
      cells. Overall, our findings provide insights into the mechanisms of action of
      hydroxytyrosol, and more generally, we identify potential gene candidates for
      further exploration.

PMID- 21953376
TI  - MRI of colorectal cancer liver metastases: comparison of orally administered
      manganese with intravenously administered gadobenate dimeglumine.
AB  - OBJECTIVES: To compare the sensitivity of MRI to detect colorectal cancer liver
      metastases (CRLM) after ingestion of manganese-based contrast agent (CMC-001)
      with that of a comprehensive intravenous gadobenate dimeglumine protocol, and to
      assess the safety and acceptability of oral manganese. METHODS: 20 patients
      suspected of having 1-6 CRLM were included prospectively in this randomised cross
      over study. Liver MRI was performed with a one-week interval at 1.5 T and
      included T1-w VIBE and T2-HASTE, before and after administration of 1.6 g CMC-001
      or 0.1 mmol/kg gadobenate dimeglumine. The metastasis-to-liver signal intensity
      (SI) ratio was calculated. Standard of reference was histopathology after
      surgery, or combination of other imaging studies and/or follow up. Adverse events
      (AE) and clinicolaboratory tests were monitored. RESULTS: Of 44 metastases, 41
      were detected after CMC-001 (93%) and 42 after gadobenate dimeglumine (95%).
      Fifteen false-positive lesions were found after CMC-001 and 2 after gadobenate
      dimeglumine. The metastasis-to-liver SI ratio was significantly higher after CMC
      001 than after gadobenate dimeglumine (0.51 and 0.21 respectively, P < 0.0001).
      More AE occurred after manganese compared to gadobenate dimeglumine. CONCLUSIONS:
      CMC-001 is as sensitive as an extensive intravenous gadobenate dimeglumine
      protocol in detecting CRLM. It was relatively well tolerated but had higher rates
      of gastrointestinal AE. KEY POINTS: * Liver MRI after ingestion of manganese is
      highly sensitive for detecting metastases * High false-positive rate necessitates
      further evaluation, in some cases * The MR examination time is short * Oral
      ingestion of manganese seems safe and relatively well tolerated by patients *
      Manganese compounds may be useful for liver metastasis surveillance after
      colorectal cancer.

PMID- 21953378
TI  - Disentangling vitality, well-being, and quality of life: a conceptual examination
      emphasizing their similarities and differences with special application in the
      physical activity domain.
AB  - BACKGROUND: Given trends toward studying positive mental health in the behavioral
      sciences, the concepts of vitality, well-being, and quality of life (QoL) have
      received significant attention. Unfortunately, interpreting their empirical
      findings and applications is difficult given a tendency to use these terms
      synonymously and/or without clear apriori definitions. METHODS: This review
      presents an in-depth, critical examination of vitality, well-being, and QoL
      (especially health-related QoL) while paying particular attention to their
      similarities and differences. Given the proliferation of studies in the area of
      physical activity psychology, this review draws from a collection of knowledge in
      the physical activity domain to provide readers with concrete examples and to
      support arguments that are raised. RESULTS: The narrative content is divided into
      3 sections with critical appraisals of each: definitions and meaning, theoretical
      views, and research, the latter of which is further subdivided into measurement
      and findings. Several parallels and discrepancies between the constructs are
      brought forward. CONCLUSIONS: Important arguments, among others, include the
      precision or specificity of the definition of vitality compared with well-being
      and QoL, and the emergence of a spectrum along which these constructs can be
      aligned with regards to the breadth of internal and external experiences they
      capture.

PMID- 21953377
TI  - Are either or both hyperuricemia and xanthine oxidase directly toxic to the
      vasculature? A critical appraisal.

PMID- 21953380
TI  - Sonographic diagnosis of a posttraumatic arteriocavernosal fistula resulting in
      high-flow priapism.
AB  - We present a case of high-flow priapism due to perineal trauma and subsequent
      arteriocavernosal fistula, which was diagnosed by sonography. Selective arterial
      embolization led to complete detumescence without compromising the patient's
      erectile function. Color Doppler sonography is an appropriate diagnostic tool to
      diagnose arteriocavernosal fistula. Selective arterial embolization is a safe and
      effective therapeutic option.

PMID- 21953379
TI  - Graft-dependent differences in the ligamentization process of anterior cruciate
      ligament grafts in a sheep trial.
AB  - PURPOSE: The structural properties of the healing ligament are the determining
      factor for the stability of the reconstruction before, during, and after osseous
      integration of anterior cruciate ligament grafts. Over the course of
      ligamentization, the stability of synovialized grafts seems lower than that of
      non-synovialized patellar tendon grafts. METHODS: In an animal study on 42 sheep,
      21 non-synovialized grafts (patellar tendon) and 21 synovialized grafts (flexor
      digitorum superficialis tendon) were performed to replace the anterior cruciate
      ligament. After 6, 12, and 24 weeks, 7 animals from each group were euthanized
      and investigated. Anteroposterior stability of the knee was assessed. After
      removal of all other soft tissues, the ACL was loaded to failure. Histology and
      histological analysis of the intra-articular graft region was then performed.
      RESULTS: There were no significant differences in the translation test comparing
      synovialized and non-synovialized grafts. After 6, 12, and 24 weeks, all
      transplants failed in the tensile test due to interligamentous rupture or
      avulsion. After 6 weeks, transplants did not show significant biomechanical
      differences. Load to failure and stiffness of the patellar tendon was more than
      twice those of synovialized tendon (P = 0.002) after 12 weeks. Histology revealed
      necrosis in patellar tendon specimens after 12 weeks. A significant increase in
      load to failure was determined in synovialized ligament grafts between 12 and 24
      weeks (P = 0.005). Its load capacity then tended to be higher than that of
      patellar tendon grafts. CONCLUSION: The stability of synovialized ligament grafts
      is significantly lower than that of non-synovialized patellar tendon grafts after
      12 weeks. This difference is compensated after 24 weeks. The significantly lower
      load to failure of synovialized compared with non-synovialized grafts after 12
      weeks may be clinically relevant for the rehabilitation process of anterior
      cruciate ligament grafts in humans.

PMID- 21953381
TI  - The cortisol awakening response (CAR) in 2- to 4-year-old children: effects of
      acute nighttime sleep restriction, wake time, and daytime napping.
AB  - The cortisol awakening response (CAR) is presumed critically important for
      healthy adaptation. The current literature, however, is hampered by systematic
      measurement difficulties relative to awakening, especially with young children.
      While reports suggest the CAR is smaller in children than adults, well-controlled
      research in early childhood is scarce. We examined whether robust CARs exist in 2
      to 4-year-old children and if sleep restriction, wake timing, and napping
      influence the CAR (n = 7). During a 25-day in-home protocol, researchers
      collected four salivary cortisol samples (0, 15, 30, 45 min post-wake) following
      five polysomnographic sleep recordings on nonconsecutive days after 4 hr (morning
      nap), 7 hr (afternoon nap), 10 hr (evening nap), 13 hr (baseline night), and 16
      hr (sleep restriction night) of wakefulness (20 samples/child). The CAR was
      robust after nighttime sleep, diminished after sleep restriction, and smaller but
      distinct after morning and afternoon (not evening) naps. Cortisol remained
      elevated 45 min after morning and afternoon naps. .

PMID- 21953382
TI  - Investigation of photoplethysmographic signals  and blood oxygen saturation
      values obtained from human splanchnic organs using a fiber optic sensor.
AB  - OBJECTIVE: A reliable, continuous method of monitoring splanchnic organ oxygen
      saturation could allow for the early detection of malperfusion, and may prevent
      the onset of multiple organ failure. Current monitoring techniques have not been
      widely accepted in critical care monitoring. As a preliminary to developing a
      continuous indwelling device, this study evaluates a new handheld fiber optic
      photoplethysmographic (PPG) sensor for estimating the blood oxygen saturation
      (SpO(2)) of splanchnic organs during surgery. METHODS: A fiber optic splanchnic
      PPG sensor, instrumentation system and virtual instrument were developed to
      facilitate PPG and SpO(2) measurement from splanchnic organs. Following Local
      Research Ethics Committee approval, the sensor was evaluated on seventeen ASA 1
      and 2 patients undergoing open laparotomy. PPG signals were obtained from the
      large bowel, small bowel, liver and stomach. Simultaneous PPG signals from the
      finger were also obtained using an identical fiber optic sensor. RESULTS: Good
      quality PPG signals with high signal-to-noise (SNR) ratios were obtained from all
      splanchnic sites under investigation. Analysis of the ac and dc amplitudes of the
      red and infrared PPG signals showed there to be a statistically significant
      difference between PPG signals obtained from splanchnic organs with those
      obtained from the finger (using fiber optic sensors). Estimated SpO(2) values
      from the splanchnic organs show good agreement with those obtained from the
      finger using both a fiber optic sensor and a commercial device. Furthermore, the
      results of a Bland and Altman analysis indicate that fiber optic splanchnic pulse
      oximetry, particularly of the bowel, may provide a suitable method for monitoring
      splanchnic organ perfusion. CONCLUSION: The evaluation of a new fiber optic
      sensor on anaesthetized patients undergoing laparotomy demonstrated that good
      quality PPG signals and SpO(2) estimates can be obtained from splanchnic organs.
      Such a sensor may provide a useful tool for the intraoperative assessment of
      splanchnic perfusion.

PMID- 21953383
TI  - The evolutionary importance of cell ratio between notochordal and nucleus
      pulposus cells: an experimental 3-D co-culture study.
AB  - INTRODUCTION: Notochordal cells and nucleus pulposus cells are co-existing in the
      intervertebral disc at various ratios among different mammalians. This fact rises
      the question about the interactions and the evolutionary relevance of this
      phenomenon. It has been described that these relatively large notochordal cells
      are mainly dominant in early lifetime of all vertebrates and then differences
      occur with ageing. Human, cattle, sheep, and goat lose the cells with age,
      whereas rodents and lagomorphs maintain these throughout their lifetime.
      MATERIALS AND METHODS: Here, we addressed the importance of cell ratio using
      alginate bead 3-D co-culture of bovine nucleus pulposus cells (bNPC) and porcine
      notochordal cells (pNCs) for 14 days using culture inserts. RESULT: We found a
      significant stimulation of bNPC in the presence of pNC in terms of cell activity
      and glycosaminoglycan production, but not for proliferation (DNA content).
      Relative gene expression was significantly stimulated for collagen type 2 and
      aggrecan. CONCLUSION: The stimulating effect of NC was confirmed and the ideal
      ratio of NPC: NC was found to be ~50:50. This has direct implications for tissue
      engineering approaches, which aim to repopulate discs with NP-like precursor
      cells.

PMID- 21953385
TI  - Special corner on "cognitive robotics".

PMID- 21953387
TI  - A homogeneous assay to assess GABA transporter activity.
AB  - This unit describes a convenient functional uptake assay for GABA transport into
      cell lines transiently transfected with GABA transporter-1 (GAT-1) and other GAT
      isoforms. This facile, homogeneous assay allows for the determination of K(m),
      V(max), and K(i) values. The assay utilizes commercially available microtiter
      plates that contain scintillant embedded in the bottom of the wells. Whereas a
      signal is generated as the cell accumulates the labeled neurotransmitter, label
      in the medium is undetected. While GABA uptake is observed in several cell lines
      transfected with GAT-1, K(m) values for GABA uptake may vary with the cell line.
      This indicates that the choice of cell line is an important consideration when
      conducting uptake assays.

PMID- 21953386
TI  - Physical activity and its related motivational attributes in adolescents with
      different BMI.
AB  - BACKGROUND: A number of obesity studies have been focused on identifying the
      relationships between socioeconomic status and physical activity involvement. In
      behavioral medicine, the limited data are available on obese people's physical
      activity and its related psychological predictors based on psychological
      theories. PURPOSE: To identify the differences in physical activity and its
      related motivational attributes among normal weight, overweight, and obese
      adolescents and to find the effect of body mass index (BMI) and the Self
      Determination Theory (SDT) constructs in predicting physical activity. METHOD:
      One thousand seventy-one students ranging from seventh to ninth grades were
      randomly selected from three junior high schools in Seoul (359 normal weight
      students, 468 overweight students, and 244 obese students). A Korean version of
      Behavioral Regulation in Exercise Questionnaire-2 and Leisure Time Exercise
      Questionnaire were applied to measure the participants' motivational attributes
      and physical activity. RESULTS: Overweight and obese adolescents showed higher
      scores on amotivation and externally motivated regulations for physical activity
      than their normal weight counterparts. Internal regulation was more significant
      for physical activity in normal weight adolescent. However, there was no
      difference in physical activity among the three groups. Additionally, the
      findings identified that BMI and the SDT constructs were significant to explain
      physical activity. CONCLUSION: This study offers fundamental knowledge in gaining
      a clearer understanding of the types of motivation most likely to contribute to
      the initiation and promotion of physical activity in overweight and obese
      adolescents.

PMID- 21953388
TI  - Functional screening in the melanophore bioassay.
AB  - The melanophore bioassay is a robust, sensitive, and versatile procedure for
      screening G protein-coupled receptors in a variety of formats. Because
      melanophores contain a wide variety of G proteins, they can be employed as a
      sensitive, real-time response system for studying transfected receptors and for
      defining equilibria for drug effects. This assay can be run in 96-well microtiter
      plates or in open-lawn 1536 format, and can yield conventional agonist-antagonist
      as well as constitutive assays.

PMID- 21953389
TI  - Adenylyl and guanylyl cyclase assays.
AB  - This unit presents two basic protocols to determine adenylyl cyclase and guanylyl
      cyclase activity in tissue and cell homogenates, permeabilized cells, or
      subcellular fractions. Each method is divided into two parts: the enzyme reaction
      that causes the formation of the labeled cyclic nucleotide, and the separation of
      cyclic nucleotide products from unreacted nucleotide triphosphates and
      metabolites using Dowex 50 resin and aluminum oxide chromatographies. In the case
      of guanylyl cyclase, alternative separation protocols are also provided.
      Additionally, protocols are provided that describe preparation of both the
      columns used in the assays and the tissue or cells to be assayed.

PMID- 21953390
TI  - Assay of receptor-stimulated phosphoinositide turnover.
AB  - The stimulation of phosphoinositide turnover is one of the key means by which
      receptors evoke responses in target cells and tissues. This is true for both G
      protein-coupled receptors and receptors that couple via tyrosine kinase activity.
      The protocols in this unit allow for pharmacological analysis of receptors
      coupled to phosphoinositide turnover. In general, the [(3)H]myo-inositol
      prelabeling methodology (described for both tissue slices and cultured cells) is
      the more widely applicable, since it requires fewer experimental steps and
      typically gives rise to a better signal-to-noise ratio. Individual inositol
      phosphates can also be determined as described by chromatographic separation on
      ion-exchange columns. In some circumstances (for example, when rapid responses to
      receptor stimulation are to be investigated or when the absolute levels of the
      active inositol phosphate are to be examined), it is preferable to use the mass
      assay described here for inositol (1,4,5)-trisphosphate from either tissue slices
      and cultured cells. This unit also provides support protocols for the preparation
      of [(3)H]myo-inositol, chromatography columns, tissue slices, and the IP(3)
      binding protein.

PMID- 21953391
TI  - Measurement and characterization of energy expenditure as a tool in the
      development of drugs for metabolic diseases, such as obesity and diabetes.
AB  - The need for treatment of obesity and obesity-related diseases, such as type 2
      diabetes, has been intensified by the epidemic rise of obesity. Recent advances
      make possible continuous monitoring of metabolically relevant functions in
      animals to identify novel thermogenic and anorectic compounds. This unit
      describes non-invasive in vivo calorimetric assessment of energy expenditure
      using measurements of oxygen consumption and carbon dioxide production,
      complemented by telemetric monitoring of body core temperature and locomotor
      activity in mice and rats. Reference compounds are used to illustrate the
      determination of substance-specific parameters, such as the dose that produces
      the half-maximal effect (ED(50)), the maximal effect, as well as the time of
      onset and duration of compound action. Indirect calorimetry performed at
      different temperatures provides information on several other well-defined
      parameters, including resting metabolic rate, basal metabolic rate, lower
      critical temperature, temperature sensitivity, defended body temperature, and
      respiratory quotient.

PMID- 21953392
TI  - Measurement and characterization of energy intake in the mouse.
AB  - Because of the dramatic increase in obesity and related conditions, such as type
      2 diabetes, efforts have intensified to develop medications to assist in losing
      weight or in minimizing weight gain. To this end, methods that allow for the
      continuous monitoring of metabolically relevant functions in laboratory animals
      have been developed to help identify novel anorectic and thermogenic agents.
      Described in this unit is an in vivo procedure for simultaneous recording of
      feeding, drinking, and motor activity in mice. Data obtained using reference
      compounds are presented to illustrate how results are calculated, including the
      minimum effective dose and the dose producing a half-maximal effect (ED(50)), as
      well as the time of onset and duration of action. Information derived from this
      procedure reveals the specificity of an anorectic effect, which, when combined
      with parameters of meal patterns, allows for inferences to be made about the
      effects of test compounds on satiety and hunger.

PMID- 21953393
TI  - Animal models of erectile dysfunction.
AB  - The neuroanatomy of the rat, as well as the morphology of the rat corpus
      cavernosum, is well characterized. Several molecular biological methods, as well
      as in vitro preparations, are available for the corpus cavernosum (CC) from rats
      or mice, and functional investigations of the erectile tissues from these species
      have revealed similar responses to activation of nerves, endothelium, or
      pharmacological agents compared with other mammals. By recording intracavernous
      pressure (ICP), erectile responses to stimulation of nerves at peripheral sites
      can be evaluated objectively in anesthetized animals. It is thereby possible to
      isolate and study the effects of regulatory mechanisms of the autonomic nervous
      system on erection, and to quantify the effect of pharmacological modulation on
      nerve-induced responses as changes in ICP. In the conscious rodent model,
      erectile responses include activities in supraspinal and spinal regulatory units,
      which lead to activation of both autonomic and somatic pathways destined for the
      CC or the penile striated muscles. These components can be evaluated by recording
      ICP in conscious animals, allowing the investigator to avoid possible deleterious
      effects of anesthesia on supraspinal and spinal transmitter pathways that may be
      involved in the regulation of erection.

PMID- 21953394
TI  - MPTP-induced models of Parkinson's disease in mice and non-human primates.
AB  - The pro-toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is widely used
      to create animal models of Parkinson's disease. This unit describes protocols for
      the production of stable and substantial lesions in the dopaminergic
      nigrostriatal pathway of mice and non-human primates. The models can be employed
      for assessing the neural mechanisms underlying the development of Parkinson's
      disease and for screening potential therapies for the treatment of this
      condition.

PMID- 21953395
TI  - Overview of pharmacokinetics.
AB  - In addition to having potency against the molecular target, a compound must be
      able to reach its intended site of action in vivo in sufficient quantity and for
      the appropriate duration to exert a biological effect. The fate of a compound
      after in vivo administration depends upon the absorption, distribution,
      metabolism, and excretion (ADME) of the compound, and the concentration of the
      compound in the blood, plasma, or other tissues represents the sum of all of
      these processes. Described in this unit are protocols for administering a
      compound by a variety of routes and for collecting the appropriate samples to
      determine the pharmacokinetic profile. The basic terms used in pharmacokinetic
      studies are defined, and representative examples are given to illustrate
      important variables to consider.

PMID- 21953396
TI  - Overview of anti-infective drug development.

PMID- 21953397
TI  - Overview of antibacterial target selection.

PMID- 21953398
TI  - Basic microbiological techniques used in antibacterial drug discovery.

PMID- 21953399
TI  - Primary rodent infection models for testing antibacterial compound efficacy in
      vivo.

PMID- 21953400
TI  - Overview of signal transduction.
AB  - Receptor- and ion channel-coupled signal transduction mechanisms are downstream
      communication processes used by regulatory molecules to modulate the essential
      cell processes of growth, differentiation and survival. Knowledge of signal
      transduction processes has dramatically increased in the past decade, and the
      basic principles of intracellular signaling are now quite well established. Cell
      signaling in higher organisms is a major, highly complex, phenomena that occupies
      a central position in current biomedical research. The complex machinery of
      intracellular signaling also has the potential to provide a wealth of novel drug
      discovery targets, from protein kinases, adaptor proteins, lipases, and
      cytoskeletal proteins, to nuclear effectors. This overview describes common
      features of cellular signaling pathways, including their interactions and
      responses to environmental stimuli. In particular, the overview focuses on the
      regulation of signaling pathways by protein functional-domain interactions as
      well as the intracellular proteins that mediate signal transduction.

PMID- 21953401
TI  - Competing risks and the clinical community: irrelevance or ignorance?
AB  - Life expectancy has dramatically increased in industrialized nations over the
      last 200 hundred years. The aging of populations carries over to clinical
      research and leads to an increasing representation of elderly and multimorbid
      individuals in study populations. Clinical research in these populations is
      complicated by the fact that individuals are likely to experience several
      potential disease endpoints that prevent some disease-specific endpoint of
      interest from occurrence. Large developments in competing risks methodology have
      been achieved over the last decades, but we assume that recognition of competing
      risks in the clinical community is still marginal. It is the aim of this article
      to address translational aspects of competing risks to the clinical community. We
      describe clinical populations where competing risks issues may arise. We then
      discuss the importance of agreement between the competing risks methodology and
      the study aim, in particular the distinction between etiologic and prognostic
      research questions. In a review of 50 clinical studies performed in individuals
      susceptible to competing risks published in high-impact clinical journals, we
      found competing risks issues in 70% of all articles. Better recognition of issues
      related to competing risks and of statistical methods that deal with competing
      risks in accordance with the aim of the study is needed.

PMID- 21953402
TI  - Effect of seabuckthorn (Hippophae rhamnoides ssp. sinensis) leaf extract on the
      swimming endurance and exhaustive exercise-induced oxidative stress of rats.
AB  - BACKGROUND: Seabuckthorn (SBT) leaves have significant antioxidant,
      immunomodulatory and anti-inflammatory properties. The objective of this study
      was to assess the anti-fatigue, antioxidant and tissue-protective properties of
      aqueous lyophilised extracts of SBT dried leaves in the hearts of Wistar male
      rats undergoing exhaustive physical exercise. Doses of 50, 200 and 800 mg kg-1
      body weight (BW) day-1 were given orally for 1 week. A week later the rats were
      forced to swim in barrels until they were exhausted. The times were noted to
      establish the effective dose of the extracts in rats. After establishing the
      effective dose, the rats were then sacrificed and assessed for various
      biochemical parameters. RESULTS: SBT leaf aqueous extracts (200 and 800 mg kg-1
      BW) markedly prolonged the swim time of rats. Supplementation with SBT leaf
      aqueous extracts helped reduce the exhaustive exercise-induced increase in
      malondialdehyde level and selenium-dependent glutathione peroxidase activity.
      Alanine aminotransferase and creatine kinase levels were lowered in the
      exhaustive exercise with SBT treatment group (E + SBT) compared with the
      exhaustive exercise group (E). CONCLUSION: The findings suggest that SBT leaf
      aqueous extract supplements can enhance exercise capacity and protect against
      oxidative damage caused by exhaustive exercise in rats.

PMID- 21953403
TI  - Interaction of endophytic microbes with legumes.
AB  - Large numbers of bacterial and fungal endophytes have been reported from
      different plant tissues: roots, nodules, leaves, flowers and sprouts of legumes,
      with numbers ranging from few to more than 150. Endophytes can accelerate
      seedling emergence, promote plant establishment under adverse conditions and
      enhance plant growth. Endophytic microbes promote plant growth by helping plants
      in acquiring nutrients, e.g. via nitrogen fixation, phosphate solubilization or
      iron chelation, by preventing pathogen infections via antifungal or antibacterial
      agents, by outcompeting pathogens for nutrients by siderophore production, or by
      establishing the plant's systemic resistance. Further growth promotion is
      affected by producing phytohormones such as auxin or cytokinin, or by producing
      the enzyme 1-aminocyclopropane-1-carboxylate (ACC) deaminase, which lowers plant
      ethylene levels. For establishment of endophytes in different tissues, endophytic
      microbes must be compatible with the host plants and able to colonize the tissues
      of the host plants without being recognized as pathogens. A particular bacterium
      or fungus may affect plant growth and development using one or more of these
      mechanisms, and they may use different mechanisms at various times. The
      population density of endophytes is highly variable, depending mainly on the
      microbial species and host genotypes, developmental stage and environmental
      conditions. Genotypic and cultivar specific endophytes have also been reported.
      The quantum benefit derived by plants from an endophyte and vice versa is still
      not clear. It seems that the endophytic genus or species best adapted for living
      inside a plant is naturally selected. Here, we concentrate on soil or rhizosphere
      derived endophytes recruited out of a large pool of soil or rhizospheric
      microbes. Some endophytes are more aggressive colonizers and displace others, but
      seeming lack of strict specificity has been observed. However, the processes of
      host-microbe signaling and colonization and the mechanisms leading to mutual
      benefits are less-well characterized. It is still not clear which population of
      microorganisms (endophytes or rhizospheric) promotes plant growth and the way the
      interactions among endophytes influence plant productivity. Though attempts to
      know the molecular ecology and interactions are underway, a high amount of
      progress is required to fully understand the mechanism of establishment, the way
      interactions take place in planta, between different microbes and plants and
      exlusive benefits by endophytes and plants.

PMID- 21953404
TI  - Efficacy of the antiphospholipid score for the diagnosis of antiphospholipid
      syndrome and its predictive value for thrombotic events.
AB  - OBJECTIVE: To define the antiphospholipid score (aPL-S) by testing multiple
      antiphospholipid antibodies (aPL) and to evaluate its efficacy for the diagnosis
      of antiphospholipid syndrome (APS) and predictive value for thrombosis. METHODS:
      This study comprised 2 independent sets of patients with autoimmune diseases. In
      the first set of patients (n = 233), the aPL profiles were analyzed. Five
      clotting assays for testing lupus anticoagulant and 6 enzyme-linked immunosorbent
      assays (IgG/IgM anticardiolipin antibodies, IgG/IgM anti-beta(2)-glycoprotein I,
      and IgG/IgM phosphatidylserine-dependent antiprothrombin antibodies) were
      included. The association of the aPL-S with a history of thrombosis/pregnancy
      morbidity was assessed. In the second set of patients (n = 411), the predictive
      value of the aPL-S for thrombosis was evaluated retrospectively. Two hundred
      ninety-six of these patients were followed up for >2 years. The relationship
      between the aPL-S and the risk of developing thrombosis was analyzed. RESULTS: In
      the first set of patients, the aPL-S was higher in those with
      thrombosis/pregnancy morbidity than in those without manifestations of APS (P <
      0.00001). For the aPL-S, the area under the receiver operating characteristic
      curve value was 0.752. In the second set of patients, new thromboses developed in
      32 patients. The odds ratio (OR) for thrombosis in patients with an aPL-S of >=30
      was 5.27 (95% confidence interval [95% CI] 2.32-11.95, P < 0.0001). By
      multivariate analysis, an aPL-S of >=30 appeared to be an independent risk factor
      for thrombosis (hazard ratio 3.144 [95% CI 1.383-7.150], P = 0.006). CONCLUSION:
      The aPL-S is a useful quantitative index for diagnosing APS and may be a
      predictive marker for thrombosis in autoimmune diseases.

PMID- 21953405
TI  - Predoctoral prescriptive authority curricula: a training option.
AB  - The purpose of the current article is to encourage discussion among stakeholders
      about the viability and benefits of predoctoral prescriptive authority (RxP)
      training. The existing APA model curriculum for RxP training requires that such
      training is postdoctoral. However, predoctoral models are potentially viable and
      offer several distinct advantages: reducing the time and financial costs of
      training, attracting more applicants with a biopsychosocial orientation, and, as
      more individuals complete this training, enlarging the constituency for state
      prescriptive authority initiatives. Several possible predoctoral model curricula
      including the incorporation of a postdoctoral master's degree in clinical
      psychopharmacology are described within existing APA PhD program requirements,
      with suggested accommodations for PsyD programs. These are offered as
      alternatives to, rather than as replacements for, postdoctoral training for RxP.

PMID- 21953406
TI  - Human leukocyte antigen class II molecules confer both susceptibility and
      progression in Japanese patients with primary biliary cirrhosis.
AB  - Along with twin and family studies, recent genome-wide association studies
      suggest that genetic factors contribute to the susceptibility and severity of
      primary biliary cirrhosis (PBC). Although several reports have demonstrated that
      the human leukocyte antigen (HLA) DRB1*08:03 allele is associated with disease
      susceptibility in Japan, the precise analysis of HLA haplotypes and the role of
      amino acid alignment have not been fully clarified. We investigated HLA class I
      A, B, and C and HLA class II DRB1 and DQB1 alleles and haplotypes in 229 Japanese
      patients with PBC and compared them with the published data of 523 healthy
      subjects. Significant associations were found with PBC susceptibility for the
      DRB1*08:03-DQB1*06:01 (13% versus 6%; P = 0.000025; odds ratio [OR] = 2.22) and
      DRB1*04:05-DQB1*04:01 haplotypes (17% versus 13%; P = 0.044; OR = 1.38).
      Conversely, there were significant protective associations with the DRB1*13:02
      DQB1*06:04 (2% versus 5%; P = 0.00093; OR = 0.27) and DRB1*11:01-DQB1*03:01
      haplotypes (1% versus 4%; P = 0.03; OR = 0.37). The frequency of the DRB1*09:01
      DQB1*03:03 haplotype was significantly higher in patients who had received
      orthotopic liver transplantation (33% versus 11%; P = 0.0012; OR = 3.96).
      Furthermore, the frequency of serine at position 57 (P = 0.0000015; OR = 1.83) of
      the DRbetachain differed the most in patients with PBC, compared with healthy
      subjects. CONCLUSION: This study established the role of HLA haplotypes in
      determining PBC susceptibility and progression in the Japanese population.
      Further resequencing of the HLA region is required to more precisely identify the
      genetic components of PBC.

PMID- 21953408
TI  - Proliferative nodule in small congenital melanocytic naevus after childhood.

PMID- 21953407
TI  - Community Outreach and Cardiovascular Health (COACH) Trial: a randomized,
      controlled trial of nurse practitioner/community health worker cardiovascular
      disease risk reduction in urban community health centers.
AB  - BACKGROUND: Despite well-publicized guidelines on the appropriate management of
      cardiovascular disease and type 2 diabetes, the implementation of risk-reducing
      practices remains poor. This report describes the results of a randomized,
      controlled clinical trial evaluating the effectiveness of a comprehensive program
      of cardiovascular disease risk reduction delivered by nurse practitioner
      /community health worker (NP/CHW) teams versus enhanced usual care (EUC) to
      improve lipids, blood pressure, glycated hemoglobin (HbA1c), and patient
      perceptions of the quality of their chronic illness care in patients in urban
      community health centers. METHODS AND RESULTS: A total of 525 patients with
      documented cardiovascular disease, type 2 diabetes, hypercholesterolemia, or
      hypertension and levels of LDL cholesterol, blood pressure, or HbA1c that
      exceeded goals established by national guidelines were randomly assigned to
      NP/CHW (n=261) or EUC (n=264) groups. The NP/CHW intervention included aggressive
      pharmacological management and tailored educational and behavioral counseling for
      lifestyle modification and problem solving to address barriers to adherence and
      control. Compared with EUC, patients in the NP/CHW group had significantly
      greater 12-month improvement in total cholesterol (difference, 19.7 mg/dL), LDL
      cholesterol (difference,15.9 mg/dL), triglycerides (difference, 16.3 mg/dL),
      systolic blood pressure (difference, 6.2 mm Hg), diastolic blood pressure
      (difference, 3.1 mm Hg), HbA1c (difference, 0.5%), and perceptions of the quality
      of their chronic illness care (difference, 1.2 points). CONCLUSIONS: An
      intervention delivered by an NP/CHW team using individualized treatment regimens
      based on treat-to-target algorithms can be an effective approach to improve risk
      factor status and perceptions of chronic illness care in high-risk patients.

PMID- 21953409
TI  - Downregulation of CD40 signal and induction of TGF-beta by phosphatidylinositol
      mediates reduction in immunogenicity against recombinant human Factor VIII.
AB  - Factor VIII (FVIII) is an important coagulation cofactor and its deficiency
      causes Hemophilia A, a bleeding disorder. Replacement therapy using recombinant
      FVIII is currently the first line of therapy for Hemophilia A, but the
      development of neutralizing antibody is a major clinical complication for this
      therapy. Recently, it has been shown that FVIII associated with
      phosphatidylinositol (PI)-containing lipidic nanoparticles reduced development of
      neutralizing antibodies in Hemophilia A mice (Peng A, Straubinger RM, Balu-Iyer
      SV. 2010. AAPS J 12(3):473-481). Here, we investigated the underlying mechanism
      of this reduction in antibody response in culturing conditions. In vitro, PI
      interfered with the processing of FVIII by cultured dendritic cells (DC),
      resulting in a reduction in the upregulation of phenotypic costimulatory signal
      CD40. Furthermore, PI increased secretion of regulatory cytokines Transforming
      Growth Factor beta1 and Interleukin 10 (IL-10) but reduced the secretion of
      proinflammatory cytokines IL-6 and IL-17. The data suggest that PI reduces
      immunogenicity of FVIII by modulating DC maturation and inducing secretion of
      regulatory cytokines.

PMID- 21953410
TI  - Dickkopf1: a tumor suppressor or metastasis promoter?
AB  - Dickkopf1 (DKK1), a secreted inhibitor of the Wnt/beta-catenin pathway, is a
      negative regulator of bone formation. DKK1 acts as a switch that transitions
      prostate cancer bone metastases from osteolytic to osteoblastic and also is an
      active indicator of poor outcome for multiple myeloma. However, in other tumor
      types, DKK1 upregulation or overexpression suppresses tumor growth. Thus, the
      role of DKK1 in cancer appears to be diverse. This raises a question: Could the
      increased levels of DKK1 still be tumor protective when observed in high levels
      in the serum of patients? Here, we summarize the diverse, seemingly contradicting
      roles of DKK1 and attempt to explain the apparent dichotomy in its activity. We
      propose that DKK1 is a critical secreted factor that modulates microenvironment.
      Based on the location and components of the microenvironment DKK1 will support
      different outcomes.

PMID- 21953411
TI  - Identification of the translocation breakpoints in the Ts65Dn and Ts1Cje mouse
      lines: relevance for modeling Down syndrome.
AB  - Down syndrome (DS) is the most frequent genetic disorder leading to intellectual
      disabilities and is caused by three copies of human chromosome 21. Mouse models
      are widely used to better understand the physiopathology in DS or to test new
      therapeutic approaches. The older and the most widely used mouse models are the
      trisomic Ts65Dn and the Ts1Cje mice. They display deficits similar to those
      observed in DS people, such as those in behavior and cognition or in neuronal
      abnormalities. The Ts65Dn model is currently used for further therapeutic
      assessment of candidate drugs. In both models, the trisomy was induced by
      reciprocal chromosomal translocations that were not further characterized. Using
      a comparative genomic approach, we have been able to locate precisely the
      translocation breakpoint in these two models and we took advantage of this
      finding to derive a new and more efficient Ts65Dn genotyping strategy.
      Furthermore, we found that the translocations introduce additional aneuploidy in
      both models, with a monosomy of seven genes in the most telomeric part of mouse
      chromosome 12 in the Ts1Cje and a trisomy of 60 centromeric genes on mouse
      chromosome 17 in the Ts65Dn. Finally, we report here the overexpression of the
      newly found aneuploid genes in the Ts65Dn heart and we discuss their potential
      impact on the validity of the DS model.

PMID- 21953412
TI  - Molecular characterization of the translocation breakpoints in the Down syndrome
      mouse model Ts65Dn.
AB  - Ts65Dn is a mouse model of Down syndrome: a syndrome that results from chromosome
      (Chr) 21 trisomy and is associated with congenital defects, cognitive impairment,
      and ultimately Alzheimer's disease. Ts65Dn mice have segmental trisomy for distal
      mouse Chr 16, a region sharing conserved synteny with human Chr 21. As a result,
      this strain harbors three copies of over half of the human Chr 21 orthologs. The
      trisomic segment of Chr 16 is present as a translocation chromosome (Mmu17(16)),
      with breakpoints that have not been defined previously. To molecularly
      characterize the Chrs 16 and 17 breakpoints on the translocation chromosome in
      Ts65Dn mice, we used a selective enrichment and high-throughput paired-end
      sequencing approach. Analysis of paired-end reads flanking the Chr 16, Chr 17
      junction on Mmu17(16) and de novo assembly of the reads directly spanning the
      junction provided the precise locations of the Chrs 16 and 17 breakpoints at
      84,351,351 and 9,426,822 bp, respectively. These data provide the basis for low
      cost, highly efficient genotyping of Ts65Dn mice. More importantly, these data
      provide, for the first time, complete characterization of gene dosage in Ts65Dn
      mice.

PMID- 21953413
TI  - Intraarticular soluble interleukin-7 [corrected] receptor levels are increased in
      patients with rheumatoid arthritis and correlate with local mediators of
      inflammation: comment on the article by Pickens et al.

PMID- 21953414
TI  - Transurethral holmium laser intravesical tape excision following TVT procedure:
      results from seven patients in a 12-month follow-up.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of this study is to evaluate the efficacy
      and the safety of the holmium:YAG laser for intravesical mesh excision in female
      patients with urinary bladder erosion complicated tension-free vaginal tape (TVT)
      procedure. METHODS: Between June 2, 2008 and December 31, 2009, seven patients
      who underwent laser excision of an intravesically protruding tape were followed
      up every 3 months for a total period of 1 year by disease-specific
      questionnaires, physical examination, cough stress test, urine analysis, urine
      bacterial culture, ultrasound and uroflowmetry. Filling cystometry was offered
      preoperatively and at the 3rd month, while cystoscopy was offered preoperatively
      and at the 1st month. The presenting symptoms were dysuria, urgency, hematuria,
      and recurrent lower urinary tract infections. Holmium laser was used for ablation
      and removal of the tape. The postoperative period was uneventful. RESULTS: There
      was a substantial improvement in the urgency status, in the maximum flow rate (Q
      (max)) from 11.29 ml/s to 19.43 ml/s, in the voided volume (VV) from 185 ml to
      251.43 ml and in the maximum cystometric capacity (C) from 237.86 ml to 310.64 ml
      pre- and postoperative, respectively. CONCLUSIONS: Holmium laser ablation
      represents a simple, safe and efficacious procedure to manage intravesical mesh
      complications following TVT procedure.

PMID- 21953415
TI  - Update: peripheral T-cell lymphomas.
AB  - Peripheral T-cell lymphomas (PTCLs) are a group of biologically heterogeneous but
      typically aggressive diseases. Progress in understanding and developing optimal
      therapies for PTCLs has been hampered by disease rarity and only relatively
      recent recognition of the importance of the T-cell phenotype. The International
      Peripheral T-cell Lymphoma Project was a large collaborative effort to provide a
      broader understanding of prognosis. Recently, several new therapies have shown
      promise in the treatment of PTCLs.

PMID- 21953416
TI  - Engaging paediatricians in planning the training of our future workforce.
AB  - Fundamental reform to the way we train and develop our future workforce is
      planned. In order to successfully achieve change the engagement of those
      delivering care is necessary. In this study the authors used a novel
      participatory design to seek the opinions of medical students, foundation
      doctors, specialty trainees and consultants on some key statements regarding
      proposed improvements to postgraduate medical education. While there was overall
      agreement on many of the recommendations of the Temple report, some aspects were
      potentially divisive, with significant differences between the views of
      consultants and those more junior to them. This work emphasises the importance of
      engaging all members of the healthcare workforce, both present and future, in the
      reasons for, and outcomes of, healthcare reform.

PMID- 21953417
TI  - Management of a child with suspected acute septic arthritis.
AB  - Acute septic arthritis of childhood is a potentially devastating disease that
      causes permanent disability and can result in death. Traditional treatment
      consists of a prolonged course of intravenous antibiotics combined with
      aggressive surgery. However, this approach is challenged by trials showing
      satisfactory outcomes with shorter treatment and less invasive surgery.
      Diagnostic arthrocentesis alone and an antibiotic for a fortnight, including
      initial intravenous administration for 2-4 days, suffice in most non-neonatal
      cases. A good penetrating agent, such as clindamycin or a first-generation
      cephalosporin, exceptionally high doses, and administration four times a day are
      probably key factors. If the symptoms and signs subside within a few days, and
      the serum C-reactive protein level drops below 20 mg/l, the antibiotic can
      usually be safely discontinued. Methicillin-resistant Staphylococcus aureus is a
      concern, but fortunately, most strains have retained susceptibility to
      clindamycin. The above guidance is not applicable to neonates and
      immunocompromised patients who may require a different approach.

PMID- 21953418
TI  - Torque teno virus 10 isolated by genome amplification techniques from a patient
      with concomitant chronic lymphocytic leukemia and polycythemia vera.
AB  - An infectious etiology has been proposed for many human cancers, but rarely have
      specific agents been identified. One difficulty has been the need to propagate
      cancer cells in vitro to produce the infectious agent in detectable quantity. We
      hypothesized that genome amplification from small numbers of cells could be
      adapted to circumvent this difficulty. A patient with concomitant chronic
      lymphocytic leukemia (CLL) and polycythemia vera (PV) requiring therapeutic
      phlebotomy donated a large amount of phlebotomized blood to test this
      possibility. Using genome amplification methods, we identified a new isolate
      (BIS8-17) of torque teno virus (TTV) 10. The presence of blood isolate sequence 8
      17 (BIS8-17) in the original plasma was confirmed by polymerase chain reaction
      (PCR), validating the approach, since TTV is a known plasma virus. Subsequent PCR
      testing of plasmas from additional patients showed that BIS8-17 had a similar
      incidence (~20%) in CLL (n = 48) or PV (n = 10) compared with healthy controls (n
      = 52). CLL cells do not harbor BIS8-17; PCR did not detect it in CLL peripheral
      blood genomic deoxyribonucleic acid (DNA) (n = 20). CLL patient clinical outcome
      or prognostic markers (immunoglobulin heavy chain variable region [IGHV ]
      mutation, CD38 or zeta-chain associated protein kinase 70 kDa [ZAP-70]) did not
      correlate with BIS8-17 infection. Although not causative to our knowledge, this
      is the first reported isolation and detection of TTV in either CLL or PV. TTV
      could serve as a covirus with another infectious agent or TTV variant with
      rearranged genetic components that contribute to disease pathogenesis. These
      results prove that this method identifies infectious agents and provides an
      experimental methodology to test correlation with disease.

PMID- 21953419
TI  - Differences in regional brain activation patterns assessed by functional magnetic
      resonance imaging in patients with systemic lupus erythematosus stratified by
      disease duration.
AB  - The mediators of tissue damage in systemic lupus erythematosus (SLE) such as
      antibodies, cytokines and activated immune cells have direct access to most
      organs in the body but must penetrate the blood-brain barrier (BBB) to gain
      access to brain tissue. We hypothesized that compromise of the BBB occurs
      episodically such that the brain will acquire tissue damage slowly and not at the
      same rate as other organs. On the basis of these assumptions, we wished to
      determine if duration of disease correlated with brain injury, as measured with
      functional magnetic resonance imaging (fMRI), and if this was independent of
      degree of tissue damage in other organs. We investigated differences in brain
      activation patterns using fMRI in 13 SLE patients stratified by disease duration
      of <=2 years (short-term [ST]) or >=10 years (long-term [LT]). Two fMRI paradigms
      were selected to measure working memory and emotional response (fearful faces
      task). Performance in the working memory task was significantly better in the ST
      group for one and two shape recall; however, both groups did poorly with three
      shape recall. Imaging studies demonstrated significantly increased cortical
      activation in the ST group in regions associated with cognition during the two
      shape retention phase of the working memory task (P < 0.001) and increased
      amygdala (P < 0.05) and superior parietal (P < 0.01) activation in response to
      the fearful faces paradigm. In conclusion, analysis of activation patterns
      stratified by performance accuracy, differences in co-morbid disease,
      corticosteroid doses or disease activity suggests that these observed differences
      are attributable to SLE effects on the central nervous system exclusive of
      vascular disease or other confounding influences. Our hypothesis is further
      supported by the lack of correlation between regional brain abnormalities on fMRI
      and the Systemic Lupus International Collaborating Clinics (SLICC) damage index.

PMID- 21953420
TI  - Serum amyloid A directly accelerates the progression of atherosclerosis in
      apolipoprotein E-deficient mice.
AB  - Although serum amyloid A (SAA) is an excellent marker for coronary artery
      disease, its direct effect on atherogenesis in vivo is obscure. In this study we
      investigated the direct effect of SAA on promoting the formation of
      atherosclerosis in apolipoprotein E-deficient (ApoE-/-) mice. Murine SAA
      lentivirus was constructed and injected into ApoE-/- mice intravenously. Then,
      experimental mice were fed a chow diet (5% fat and no added cholesterol) for 14
      wks. The aortic atherosclerotic lesion area was larger with than without SAA
      treatment. With increased SAA levels, the plasma levels of interleukin-6 and
      tumor necrosis factor-alpha were significantly increased. Macrophage infiltration
      in atherosclerotic regions was enhanced with SAA treatment. A migration assay
      revealed prominent dose-dependent chemotaxis of SAA to macrophages. Furthermore,
      the expression of monocyte chemotactic protein-1 and vascular cell adhesion
      molecule-1 (VCAM-1) was upregulated significantly with SAA treatment. SAA-induced
      VCAM-1 production was detected in human aortic endothelial cells in vitro. Thus,
      an increase in plasma SAA directly accelerates the progression of atherosclerosis
      in ApoE-/- mice. SAA is not only a risk marker for atherosclerosis but also an
      active participant in atherogenesis.

PMID- 21953421
TI  - Prenatal sonographic monitoring of idiopathic megacystis.
AB  - This case report is of a female fetus diagnosed with severe idiopathic megacystis
      at 21 weeks of pregnancy. Sonographic monitoring demonstrated normal amniotic
      fluid volume and renal structures, absence of hydronephrosis, ureteral dilation,
      and associated abnormalities. Conservative management was chosen with postnatal
      confirmation of diagnosis. The neonate presented seizures, and subsequent
      magnetic resonance imaging demonstrated transverse sinus thrombosis with adjacent
      ischemic damage. At present, the infant is 2 years old, and she is thriving
      normally and maintains urinary continence with spontaneous voidings.

PMID- 21953422
TI  - Type 1 diabetes mellitus and celiac disease: endothelial dysfunction.

PMID- 21953423
TI  - Minimal incidence of neonatal/infancy onset diabetes in Italy is 1:90,000 live
      births.
AB  - Until early 2000, permanent and transient neonatal diabetes mellitus (NDM),
      defined as diabetes with onset within 6 weeks from birth that requires insulin
      therapy for at least 2 weeks, were considered exceedingly rare conditions, with a
      global incidence of 1:500,000-1:400,000 live births. The new definition of NDM
      recently adopted, that includes patients with diabetes onset within 6 months of
      age, has prompted studies that have set the incidence of the permanent form alone
      between 1:210,000 and 1:260,000 live births. Aim of the present work was to
      ascertain the incidence of NDM (i.e. permanent + transient form) in Italy for
      years 2005-2010. Patients referred to the Italian reference laboratory for NDM
      between years 2005 and 2010 and screened for mutations in common NDM genes
      (KCNJ11, ABCC8, and INS) and for uniparental isodisomy of chromosome 6 (UDP6)
      were reviewed. A questionnaire aimed at identifying NDM cases investigated in
      other laboratories was sent to 54 Italian reference centers for pediatric
      diabetes. Twenty-seven patients with NDM born between 2005 and 2010 were referred
      to the reference laboratory. In this group, a mutation of either KCNJ11, ABCC8 or
      INS was found in 18 patients, and a case with UDP6 was identified. Questionnaires
      revealed 4 additional cases with transient neonatal diabetes due to UDP6.
      Incidence of NDM was calculated at 1:90,000 (CI: 1:63,000-1:132,000) live births.
      Thus, with the definition currently in use, about 6 new cases with NDM are
      expected to be born in Italy each year.

PMID- 21953424
TI  - [Urologic oncology].

PMID- 21953425
TI  - [Urothelial carcinoma of the upper urinary tract: clinical and pathological
      criteria and their predictive implications after radical nephroureterectomy].
AB  - Recent multicentric studies contributed significantly to the understanding of
      clinical and pathological criteria and their implications as prognosticators of
      the upper urinary tract urothelial carcinoma. They demonstrated a large variety
      of prognosticators influencing the course of this rare disease. The influence of
      gender and age and the presence of symptoms and renal obstruction in addition to
      pathologic criteria such as staging, tumor architecture, lymphnode invasion,
      localization and the presence of CIS or tumor necrosis on prognosis and disease
      recurrence after radical nephroureterectomy were investigated. Additional
      multicentric, ideally prospective studies are warranted to validate current
      findings.

PMID- 21953426
TI  - [Systemic therapy of muscle invasive bladder cancer - an update].
AB  - Urothelial cancer is a highly common tumor with increasing incidence worldwide
      and a peak in the seventh decade. Locally advanced disease has a significant risk
      for developing metastases. Neoadjuvant, platinum-containing combination
      chemotherapy improves survival over radical cystectomy. Chemotherapy with
      gemcitabine plus cisplatin shows equivalent efficacy with less toxicity to MVAC
      in metastatic setting. New therapy strategies, especially in elderly patients,
      are urgently needed.

PMID- 21953427
TI  - [Neoadjuvant therapy before radical prostatectomy - indications and protocols].
AB  - As neoadjuvant chemotherapy is established for a variety of nonorgan confined
      malignancies, neoadjuvant hormone ablation for hormone sensitive prostate cancer
      has demonstrated encouraging results. Neoadjuvant therapy not only provides
      possible early systemic treatment for subclinical distant disease, but also aims
      to improve local disease control and to increase the number of patients eligible
      for definitive local therapy via downstaging. However, only limited, heterogenous
      studies are available. Therefore, prospective high quality studies are urgently
      needed to assess the future role of neoadjuvant hormone ablation.

PMID- 21953428
TI  - [Current treatment of locally advanced and metastatic prostate cancer].
AB  - Despite the broad use of PSA-testing in western medicine, still an estimated 1/3
      of carcinomas of the prostate (PC) are diagnosed in a locally advanced or
      metastatic stage. In the current treatment-algorithm for locally advanced PC,
      radical prostatectomy, external beam radiation therapy (with and without hormonal
      therapy) and primary androgen deprivation are available. In fact, in a majority
      of patients treatment of this tumor stage will be a multimodal approach, which
      has to be discussed individually. For metastatic PC hormonal deprivation therapy
      is still the gold standard. Beside LHRH-agonists, surgical castration and
      complete androgen deprivation today LHRH-antagonists represent the different
      therapeutic options in this tumor stage. Effects on natural course of this
      disease have to be balanced to the side effects of long-term therapy. Castration
      resistant PC is not the object of this overview even though there are a variety
      of new medical interventions emerging for the treatment of this stage of PC.

PMID- 21953429
TI  - [Systemic treatment of renal cell carcinoma - recent update].
AB  - Renal cell cancer is the most common form of all malignant renal cancers. The
      most important exogenic risk factors are smoking and obesity. Most presentations
      are incidental and, when systemic symptoms occur they are often due to
      metastases. The mortality rate is still 30% in this disease. The only curative
      treatment option is surgery. Until recently interferon alpha and/or interleukin-2
      were standard treatments in the palliative setting, but efficacy was limited. But
      in the last years advances could be made. Targeted therapies like sunitinib could
      demonstrate a significant improvement in progression free survival. Moreover,
      there are now treatment options even in second line palliative treatment.
      Nevertheless there are still enough questions to be answered: the optimal
      sequential therapy, how long should we treat our patients and can we combine
      theses targeted therapies? Studies to answer all these burning questions are
      already ongoing.

PMID- 21953430
TI  - Pre-competition cardiac screening in professional handball players - setting up
      at the EHF European Handball Championship 2010 in Austria.
AB  - In many sports, regular cardiac screening for exercise-associated sudden cardiac
      death is still not provided. To set up the current situation in top-skilled
      handball players qualified for the 2010 European Handball Championship in
      Austria, a standardised questionnaire was sent to every team. The fact that only
      42.7% of the players returned the questionnaire may lead to the conclusion that
      the awareness of the problem is quite low. However, 82% of these players have
      been screened according to current recommendations. Half of the teams were
      screened inhomogeneously: 5 players (4.1%) have not been screened within the last
      years, 1 athlete (0.8%) was screened without an ECG. While 69% of the athletes
      got their first screening only after the age of 18, 16 players (13.1%) never went
      through a specific screening ever. We identified 17 athletes (13.9%) with a
      highly suspicious history, 2 of them (1.6%) never underwent a medical screening
      at all.

PMID- 21953431
TI  - Incidental finding of a splenic hamartoma with tumour-like extramedullary
      erythropoiesis.
AB  - Hamartomas of the spleen are rare benign tumour-like lesions that tend to be
      asymptomatic incidental findings. Splenic hamartomas with tumour-like
      extramedullary erythropoiesis are extremely rare. A 70-year-old male patient with
      dyspnoea and a nodular intrapulmonary lesion morphologically verified by CT
      underwent fibre bronchoscopy, which showed a pea-shaped foreign body that was
      retrieved without complication. As a secondary finding, the CT showed a splenic
      lesion of about 8 cm in size. An MR study showed an expansive process in the
      center of the spleen. The patient was completely free of clinical symptoms.
      Because of the unknown nature and the high risk for spontaneous rupture of the
      lesion, a splenectomy was performed. The histological analyses revealed tumour
      like extramedullary erythropoiesis of the spleen. The patient was discharged in
      good condition ten days postoperatively. A hamartoma of the spleen with
      extramedullary tumor-like erythropoiesis should be considered in the differential
      diagnosis of a splenic lesion.

PMID- 21953432
TI  - [Commentary on the planned restructuring of mammography screening in Austria].
AB  - With regards to the planned reorganisation of screening mammography in Austria -
      from an opportunistic to an organised system - the problems related with such a
      change are depicted from an epidemiological point of view. We were able to
      demonstrate earlier that opportunistic screening mammography matches the results
      of controlled screening mammography in Finland and Sweden. Switching to a
      controlled system in Austria would - besides the need for a change in legislation
      - lead to enormous expenditures in terms of resources needed and moreover, it
      could be not evaluated for years.

PMID- 21953434
TI  - Abstracts of the Annual Meeting of the Canadian Anesthesiologists' Society. June
      24-28, 2011. Toronto, Ontario, Canada.

PMID- 21953433
TI  - Eyeblink conditioning in the developing rabbit.
AB  - Eyeblink classical conditioning in pre-weanling rabbits was examined in the
      present study. Using a custom lightweight headpiece and restrainer, New Zealand
      white littermates were trained once daily in 400 ms delay eyeblink classical
      conditioning from postnatal days (PD) 17-21 or PD 24-28. These ages were chosen
      because eyeblink conditioning emerges gradually over PD 17-24 in rats [Stanton et
      al., (1992) Behavioral Neuroscience, 106(4):657-665], another altricial species
      with neurodevelopmental features similar to those of rabbits. Consistent with
      well-established findings in rats, rabbits trained from PD 24-28 showed greater
      conditioning relative to littermates trained from PD 17-21. Both age groups
      displayed poor retention of eyeblink conditioning at retraining 1 month after
      acquisition. These findings are the first to demonstrate eyeblink conditioning in
      the developing rabbit. With further characterization of optimal conditioning
      parameters, this preparation may have applications to neurodevelopmental disease
      models as well as research exploring the ontogeny of memory.

PMID- 21953435
TI  - Synthesis and photo-physical characteristics of ESIPT inspired 2-substituted
      benzimidazole, benzoxazole and benzothiazole fluorescent derivatives.
AB  - Novel 2-(1H-benzimidazol-2-yl)-5-(N,N-diethylamino) phenol, 2-(1,3-benzoxazol-2
      yl)-5-(N,N-diethylamino) phenol, 2-(1,3-benzothiazol-2-yl)-5-(N,N-diethylamino)
      phenol and their derivatives have been synthesized from p-N,N-diethyl amino
      salicylaldehyde with different substituted o-phenylenediamine or o-aminophenol or
      o-aminothiophenol and their photo-physical properties were studied. Effects of
      solvent polarity in the absorption-emission properties of synthesized compounds
      were investigated. All these compounds shows excited state intra-molecular proton
      transfer pathway having single absorption and dual emission characteristics. The
      fluorescent compounds were characterised by FT-IR, (1)HNMR, (13)C NMR and Mass
      spectral analysis. TGA analysis showed these compounds are thermally stable up to
      200  degrees C.

PMID- 21953436
TI  - Photoluminescence and energy transfer study of Eu3+ codoped with CdS
      nanoparticles in silica glass.
AB  - The CdS nanoparticles along with Eu(3+) ions were embedded in silica xerogel by
      sol gel technique. The samples were studied by TGA, DTA and fluorescence
      techniques. The result suggested that doping of CdS nanoparticles enhanced the
      luminescence properties of Eu(3+) even in the gel stage itself and this avoids
      the need of heating gel at higher temperature. The effects of CdS nanoparticles
      on the Eu(3+) luminescence were discussed.

PMID- 21953437
TI  - Spectrofluorimetric determination of aliskiren in tablets and spiked human plasma
      through derivatization with dansyl chloride.
AB  - A simple and sensitive method has been developed and validated for the
      determination of aliskiren (ALS) in its dosage forms and spiked plasma. The
      method was based on the reaction of the drug with dansyl chloride in the presence
      of bicarbonate solution of pH 10.5 to give a highly fluorescent derivative which
      was measured at 501 nm with excitition at 378 nm in dichloromethane. Different
      experimental parameters affecting the development of the method and stability
      were carefully studied and optimized. The calibration curves were linear over the
      concentration ranges of 100-700 and 50-150 ng/mL for standard solution and
      plasma, respectively. The limits of detection were 27.52 ng/mL in standard
      solution, 4.91 ng/mL in plasma. The developed method was successfully applied to
      the analysis the drug in the commercial tablets and spiked plasma samples. The
      mean recovery of ALS from tablets and plasma was 100.10 and 97.81%, respectively.
      A proposal of the reaction pathway was presented.

PMID- 21953438
TI  - Mitochondrial DNA analysis of Hokkaido Jomon skeletons: remnants of archaic
      maternal lineages at the southwestern edge of former Beringia.
AB  - To clarify the colonizing process of East/Northeast Asia as well as the peopling
      of the Americas, identifying the genetic characteristics of Paleolithic Siberians
      is indispensable. However, no genetic information on the Paleolithic Siberians
      has hitherto been reported. In the present study, we analyzed ancient DNA
      recovered from Jomon skeletons excavated from the northernmost island of Japan,
      Hokkaido, which was connected with southern Siberia in the Paleolithic period.
      Both the control and coding regions of their mitochondrial DNA (mtDNA) were
      analyzed in detail, and we confidently assigned 54 mtDNAs to relevant
      haplogroups. Haplogroups N9b, D4h2, G1b, and M7a were observed in these
      individuals, with N9b being the predominant one. The fact that all these
      haplogroups, except M7a, were observed with relatively high frequencies in the
      southeastern Siberians, but were absent in southeastern Asian populations,
      implies that most of the Hokkaido Jomon people were direct descendants of
      Paleolithic Siberians. The coalescence time of N9b (ca. 22,000 years) was before
      or during the last glacial maximum, implying that the initial trigger for the
      Jomon migration in Hokkaido was increased glaciations during this period.
      Interestingly, Hokkaido Jomons lack specific haplogroups that are prevailing in
      present-day native Siberians, implying that diffusion of these haplogroups in
      Siberia might have been after the beginning of the Jomon era, about 15,000 years
      before present.

PMID- 21953439
TI  - Pseudosibship methods in the case-parents design.
AB  - Recent evidence suggests that complex traits are likely determined by multiple
      loci, each of which contributes a weak to moderate individual effect. Although
      extensive literature exists on multilocus analysis of unrelated subjects, there
      are relatively fewer strategies for jointly analyzing multiple loci using family
      data. Here we address this issue by evaluating two pseudosibship methods: the 1:1
      matching, which matches each affected offspring to the pseudosibling formed by
      the alleles not transmitted to the affected offspring, and the exhaustive
      matching, which matches each affected offspring to the pseudosiblings formed by
      all the other possible combinations of parental alleles. We prove that the two
      matching strategies use exactly and approximately the same amount of information
      from data under additive and multiplicative genetic models, respectively. Using
      numerical calculations under a variety of models and testing assumptions, we show
      that compared with the exhaustive matching, the 1:1 matching has comparable
      asymptotic power in detecting multiplicative/additive effects in single-locus
      analysis and main effects in multilocus analysis, and it allows association
      testing of multiple linked loci. These results pave the way for many existing
      multilocus analysis methods developed for the case-control (or matched case
      control) design to be applied to case-parents data with minor modifications. As
      an example, with the 1:1 matching, we applied an L1 regularized regression to a
      Crohn's disease dataset. Using the multiple loci selected in our approach, we
      obtained an order-of-magnitude decrease in p-value and an 18.9% increase in
      prediction accuracy when compared with using the most significant individual
      locus.

PMID- 21953440
TI  - Enhancement of soluble dietary fibre, polyphenols and antioxidant properties of
      chapatis prepared from whole wheat flour dough treated with amylases and
      xylanase.
AB  - BACKGROUND: Chapati preparation involves various processing steps such as mixing
      the flour into dough, sheeting and baking. During these processing steps, flour
      components are likely to undergo changes in their nutrient and polyphenol
      composition and their antioxidant properties due to phenol-mediated crosslinking
      of proteins and carbohydrates. Therefore, in the present study, changes in
      nutritional, nutraceutical and antioxidant properties of chapatis prepared from
      doughs treated with amylases and xylanase were determined. RESULTS: An increase
      in insoluble dietary fibre content and a decrease in soluble polyphenol content
      were observed during preparation of control chapatis from whole wheat flours.
      However, significant increases in soluble dietary fibre and soluble polyphenol
      contents were observed in chapatis prepared from amylase-treated doughs compared
      with control chapatis. Extracts of chapatis prepared from amylase- and xylanase
      treated doughs showed better antioxidant properties than extracts of control
      chapatis. Among these enzyme treatments, chapatis prepared from amylase-treated
      doughs showed better antioxidant properties than chapatis prepared from xylanase
      treated doughs. High-performance liquid chromatography analysis of extracts of
      chapatis prepared from doughs treated with amylases showed the presence of
      potential antioxidant phenolic acids such as caffeic, gentisic and syringic acids
      in addition to the phenolic acids present in control chapatis. CONCLUSION:
      Treatment of doughs with amylases increased the contents of soluble dietary fibre
      and soluble polyphenols as well as improving the antioxidant properties of
      chapatis.

PMID- 21953441
TI  - Treatment failure in behavior therapy: focus on behavioral activation for
      depression.
AB  - Behavioral activation (BA) has come to be recognized as an empirically supported
      treatment for depression. Despite the general success of the approach, many
      patients experience treatment failure. Based on behavioral models of depression,
      we present several reasons for treatment failure in BA, including patient
      inability to understand and adopt the treatment rationale, lack of awareness or
      ability to articulate and behave according to life values, behavioral
      noncompliance, and ineffectiveness of contingency management to increase exposure
      to environmental rewards and reduce contact with both aversive environmental
      events and reinforcement of depressed behavior. A case study of treatment failure
      with a depressed breast cancer patient is presented, along with recommendations
      to reduce failure rates in BA.

PMID- 21953443
TI  - c-myb mediates inflammatory reaction against oxidative stress in human breast
      cancer cell line, MCF-7.
AB  - Emerging evidence suggests that oncogenes play an important role in the
      inflammatory reactions in cancer cells, but the precise molecular and cellular
      mechanisms linking the oncogenes to inflammation is unclear. This study examined
      the contribution of proto-oncogene c-myb to inflammation in MCF-7 breast cancer
      cells. An inflammatory response was elicited directly by the cells using an in
      vitro culture system whereby the cells were exposed to H(2) O(2) . Upon exposure
      to H(2) O(2) , the cells showed a local inflammatory response, as evidenced by
      matrix metalloproteinases (MMPs) and ICAM-1 expression. Significant up-regulation
      of the proto-oncogene c-myb also was observed under inflammatory conditions. c
      myb, overexpressed in the cells by transducing with Ad/c-myb, showed an increase
      in MMPs and ICAM-1 expression under H(2) O(2) stimulation. Despite H(2) O(2)
      stimulation, the c-myb down-regulated cells by c-myb siRNA inhibit the expression
      of MMPs and ICAM-1. Among the MAPKs, ERK1/2 and SAPK/JNK were activated by the
      H(2) O(2) treatment. Interestingly, the H(2) O(2) -induced activation of ERK1/2
      and SAPK/JNK was inhibited by siRNA c-myb. These results suggest that breast
      cancer cells may play a significant role in sustaining and amplifying the
      inflammation process through the activation of c-myb, which results in the
      activation of the ERK1/2 and SAPK/JNK pathway. This condition highlights the
      potential link between inflammation and its involvement in promoting breast
      cancer proliferation.

PMID- 21953442
TI  - Serum ferritin is an independent predictor of histologic severity and advanced
      fibrosis in patients with nonalcoholic fatty liver disease.
AB  - Serum ferritin (SF) levels are commonly elevated in patients with nonalcoholic
      fatty liver disease (NAFLD) because of systemic inflammation, increased iron
      stores, or both. The aim of this study was to examine the relationship between
      elevated SF and NAFLD severity. Demographic, clinical, histologic, laboratory,
      and anthropometric data were analyzed in 628 adult patients with NAFLD (age, >=
      18 years) with biopsy-proven NAFLD and an SF measurement within 6 months of their
      liver biopsy. A threshold SF >1.5 * upper limit of normal (ULN) (i.e., >300 ng/mL
      in women and >450 ng/mL in men) was significantly associated with male sex,
      elevated serum alanine aminotransferase, aspartate aminotransferase, iron,
      transferrin-iron saturation, iron stain grade, and decreased platelets (P <
      0.01). Histologic features of NAFLD were more severe among patients with SF >1.5
      * ULN, including steatosis, fibrosis, hepatocellular ballooning, and diagnosis of
      NASH (P < 0.026). On multiple regression analysis, SF >1.5 * ULN was
      independently associated with advanced hepatic fibrosis (odds ratio [OR], 1.66;
      95% confidence interval [CI], 1.05-2.62; P = 0.028) and increased NAFLD Activity
      Score (NAS) (OR, 1.99; 95% CI, 1.06-3.75; P = 0.033). CONCLUSIONS: A SF >1.5 *
      ULN is associated with hepatic iron deposition, a diagnosis of NASH, and worsened
      histologic activity and is an independent predictor of advanced hepatic fibrosis
      among patients with NAFLD. Furthermore, elevated SF is independently associated
      with higher NAS, even among patients without hepatic iron deposition. We conclude
      that SF is useful to identify NAFLD patients at risk for NASH and advanced
      fibrosis.

PMID- 21953444
TI  - Extracellular proteinase formation in carbon starving Aspergillus nidulans
      cultures--physiological function and regulation.
AB  - Extracellular proteinase formation in carbon depleted cultures of the model
      filamentous fungus Aspergillus nidulans was studied to elucidate its regulation
      and possible physiological function. As demonstrated by gene deletion, culture
      optimization, microbial physiological and enzymological experiments, the PrtA and
      PepJ proteinases of A. nidulans did not appear to play a decisive role in the
      autolytic decomposition of fungal cells under the conditions we tested. However,
      carbon starvation induced formation of the proteinases observable in autolytic
      cultures. Similar to other degradative enzymes, production of proteinase was
      regulated by FluG-BrlA asexual developmental signaling and modulated by PacC
      dependent pH-responsive signaling. Under the same carbon starved culture
      conditions, alterations of CreA, MeaB or heterotrimeric G protein mediated
      signaling pathways caused less significant changes in the formation of
      extracellular proteinases. Taken together, these results indicate that while the
      accumulation of PrtA and PepJ is tightly coupled to the initiation of autolysis,
      they are not essential for autolytic cell wall degradation in A. nidulans. Thus,
      as Aspergillus genomes contain a large group of genes encoding proteinases with
      versatile physiological functions, selective control of proteinase production in
      fungal cells is needed for the improved industrial use of fungi.

PMID- 21953445
TI  - Physical activity and energy expenditure in adolescent male sport participants
      and nonparticipants aged 13 to 16 years.
AB  - BACKGROUND: Sport has high social valence and is a primary context for physical
      activity for the majority of youth. The aim of this study was to estimate the
      contribution of participation in organized sport to the total daily energy
      expenditure and also to its moderate-to-vigorous portion in male adolescents.
      METHODS: The sample comprised 165 Portuguese male youth, aged 13 to 16 years.
      Physical activity was assessed with a multi-method approach (Actigraph GT1M
      accelerometer plus 3-day diary record). Differences in the intensities of
      physical activity and sedentary behavior of male sport participants and nonsport
      participants were compared using independent sample t-test. RESULTS: Male
      participants in organized sports spent significantly more time in moderate-to
      vigorous activities than nonparticipants, although the P-value for the 15 to 16
      years age-group was marginal (P = .08) on the weekend days. In addition, male
      adolescents spent 11% to 13% of total daily energy expenditure in organized
      sports which corresponded to 35% to 42% of the moderate-to-vigorous portion of
      daily energy expenditure. CONCLUSION: Organized sport appears to be a relevant
      component of daily activity energy expenditure to promote healthy lifestyles
      among male adolescents.

PMID- 21953446
TI  - Beyond the "syndrome": antiphospholipid antibodies as risk factors.

PMID- 21953447
TI  - Hemorphin as a prognostic biomarker and potential drug for breast cancer?

PMID- 21953448
TI  - Hydrogen sulfide and L-cysteine increase phosphatidylinositol 3,4,5-trisphosphate
      (PIP3) and glucose utilization by inhibiting phosphatase and tensin homolog
      (PTEN) protein and activating phosphoinositide 3-kinase (PI3K)/serine/threonine
      protein kinase (AKT)/protein kinase Czeta/lambda (PKCzeta/lambda) in 3T3l1
      adipocytes.
AB  - This work examined the novel hypothesis that reduced levels of H(2)S or L
      cysteine (LC) play a role in the impaired glucose metabolism seen in diabetes.
      3T3L1 adipocytes were treated with high glucose (HG, 25 mM) in the presence or
      absence of LC or H(2)S. Both LC and H(2)S treatments caused an increase in
      phosphatidylinositol-3,4,5 trisphosphate (PIP3), AKT phosphorylation, and glucose
      utilization in HG-treated cells. The effect of LC on PIP3 and glucose utilization
      was prevented by propargylglycine, an inhibitor of cystathionine gamma-lyase that
      catalyzes H(2)S formation from LC. This demonstrates that H(2)S mediates the
      effect of LC on increased PIP3 and glucose utilization. H(2)S and LC caused
      phosphatidylinositol 3-kinase activation and PTEN inhibition. Treatment with LC,
      H(2)S, or PIP3 increased the phosphorylation of IRS1, AKT, and PKCzeta/lambda as
      well as GLUT4 activation and glucose utilization in HG-treated cells. This
      provides evidence that PIP3 is involved in the increased glucose utilization
      observed in cells supplemented with LC or H(2)S. Comparative signal silencing
      studies with siAKT2 or siPKCzeta revealed that PKCzeta phosphorylation is more
      effective for the GLUT4 activation and glucose utilization in LC-, H(2)S-, or
      PIP3-treated cells exposed to HG. This is the first report to demonstrate that
      H(2)S or LC can increase cellular levels of PIP3, a positive regulator of glucose
      metabolism. The PIP3 increase is mediated by PI3K activation and inhibition of
      PTEN but not of SHIP2. This study provides evidence for a molecular mechanism by
      which H(2)S or LC can up-regulate the insulin-signaling pathways essential for
      maintenance of glucose metabolism.

PMID- 21953449
TI  - Collapsin response mediator proteins (CRMPs) are a new class of microtubule
      associated protein (MAP) that selectively interacts with assembled microtubules
      via a taxol-sensitive binding interaction.
AB  - Collapsin response mediator proteins are ubiquitously expressed from multiple
      genes (CRMPs 1-5) and play important roles in dividing cells and during
      semaphorin 3A (Sema3A) signaling. Nonetheless, their mode of action remains
      opaque. Here we carried out in vivo and in vitro assays that demonstrate that
      CRMPs are a new class of microtubule-associated protein (MAP). In experiments
      with CRMP1 or CRMP2 and their derivatives, only the C-terminal region (residues
      490-572) mediated microtubule binding. The in vivo microtubule association of
      CRMPs was abolished by taxol or epothilone B, which is highly unusual. CRMP2
      depleted cells exhibited destabilized anaphase astral microtubules and altered
      spindle position. In a cell-based assay, all CRMPs stabilized interphase
      microtubules against nocodazole-mediated depolymerization, with CRMP1 being the
      most potent. Remarkably, a 82-residue C-terminal region of CRMP1 or CRMP2,
      unrelated to other microtubule binding motifs, is sufficient to stabilize
      microtubules. In cells, we demonstrate that glycogen synthase kinase-3beta
      (GSK3beta) inhibition potentiates this activity. Thus, CRMPs are a new class of
      MAP that binds through a unique motif, but in common with others such as Tau, is
      antagonized by GSK3beta. This regulation is consistent with such kinases being
      critical for the Sema3A (collapsin) pathway. These findings have implications for
      cancer and neurodegeneration.

PMID- 21953450
TI  - A complex of nuclear factor I-X3 and STAT3 regulates astrocyte and glioma
      migration through the secreted glycoprotein YKL-40.
AB  - Nuclear factor I-X3 (NFI-X3) is a newly identified splice variant of NFI-X that
      regulates expression of several astrocyte-specific markers, such as glial
      fibrillary acidic protein. Here, we identified a set of genes regulated by NFI-X3
      that includes a gene encoding a secreted glycoprotein YKL-40. Although YKL-40
      expression is up-regulated in glioblastoma multiforme, its regulation and
      functions in nontransformed cells of the central nervous system are widely
      unexplored. We find that expression of YKL-40 is activated during brain
      development and also differentiation of neural progenitors into astrocytes in
      vitro. Furthermore, YKL-40 is a migration factor for primary astrocytes, and its
      expression is controlled by both NFI-X3 and STAT3, which are known regulators of
      gliogenesis. Knockdown of NFI-X3 and STAT3 significantly reduced YKL-40
      expression in astrocytes, whereas overexpression of NFI-X3 dramatically enhanced
      YKL-40 expression in glioma cells. Activation of STAT3 by oncostatin M induced
      YKL-40 expression in astrocytes, whereas expression of a dominant-negative STAT3
      had a suppressive effect. Mechanistically, NFI-X3 and STAT3 form a complex that
      binds to weak regulatory elements in the YKL-40 promoter and activates
      transcription. We propose that NFI-X3 and STAT3 control the migration of
      differentiating astrocytes as well as migration and invasion of glioma cells via
      regulating YKL-40 expression.

PMID- 21953451
TI  - Identification of nicotinamide mononucleotide deamidase of the bacterial pyridine
      nucleotide cycle reveals a novel broadly conserved amidohydrolase family.
AB  - The pyridine nucleotide cycle is a network of salvage and recycling routes
      maintaining homeostasis of NAD(P) cofactor pool in the cell. Nicotinamide
      mononucleotide (NMN) deamidase (EC 3.5.1.42), one of the key enzymes of the
      bacterial pyridine nucleotide cycle, was originally described in Enterobacteria,
      but the corresponding gene eluded identification for over 30 years. A genomics
      based reconstruction of NAD metabolism across hundreds of bacterial species
      suggested that NMN deamidase reaction is the only possible way of nicotinamide
      salvage in the marine bacterium Shewanella oneidensis. This prediction was
      verified via purification of native NMN deamidase from S. oneidensis followed by
      the identification of the respective gene, termed pncC. Enzymatic
      characterization of the PncC protein, as well as phenotype analysis of deletion
      mutants, confirmed its proposed biochemical and physiological function in S.
      oneidensis. Of the three PncC homologs present in Escherichia coli, NMN deamidase
      activity was confirmed only for the recombinant purified product of the ygaD
      gene. A comparative analysis at the level of sequence and three-dimensional
      structure, which is available for one of the PncC family member, shows no
      homology with any previously described amidohydrolases. Multiple alignment
      analysis of functional and nonfunctional PncC homologs, together with NMN docking
      experiments, allowed us to tentatively identify the active site area and
      conserved residues therein. An observed broad phylogenomic distribution of
      predicted functional PncCs in the bacterial kingdom is consistent with a possible
      role in detoxification of NMN, resulting from NAD utilization by DNA ligase.

PMID- 21953452
TI  - Membrane curvature sensing by amphipathic helices: a single liposome study using
      alpha-synuclein and annexin B12.
AB  - Preferential binding of proteins on curved membranes (membrane curvature sensing)
      is increasingly emerging as a general mechanism whereby cells may effect protein
      localization and trafficking. Here we use a novel single liposome fluorescence
      microscopy assay to examine a common sensing motif, the amphipathic helix (AH),
      and provide quantitative measures describing and distinguishing membrane binding
      and sensing behavior. By studying two AH-containing proteins, alpha-synuclein and
      annexin B12, as well as a range of AH peptide mutants, we reveal that both the
      hydrophobic and hydrophilic faces of the helix greatly influence binding and
      sensing. Although increased hydrophobic and electrostatic interactions with the
      membrane both lead to greater densities of bound protein, the former yields
      membrane curvature-sensitive binding, whereas the latter is not curvature
      dependent. However, the relative contributions of both components determine the
      sensing of AHs. In contrast, charge density in the lipid membrane seems important
      primarily in attracting AHs to the membrane but does not significantly influence
      sensing. These observations were made possible by the ability of our assay to
      distinguish within our samples liposomes with and without bound protein as well
      as the density of bound protein. Our findings suggest that the description of
      membrane curvature-sensing requires consideration of several factors such as
      short and long range electrostatic interactions, hydrogen bonding, and the volume
      and structure of inserted hydrophobic residues.

PMID- 21953453
TI  - Identification of a novel Mcl-1 protein binding motif.
AB  - Recent characterization of Mcl-1 as the primary anti-apoptotic Bcl-2 family
      member expressed in solid tumors, coupled with its ability to enable therapeutic
      resistance, has provided the impetus for further study into how Mcl-1 is involved
      in apoptosis signaling. Here, we employ Sabutoclax, a potent and effective Mcl-1
      antagonist, as a competing agent to screen a randomized 12-residue phage display
      library for peptides that bind strongly to the Bcl-2 homology 3 (BH3) binding
      groove of Mcl-1. Although the screen identified a number of alpha-helical
      peptides with canonical BH3 domain sequences, it also isolated a pair of unique
      peptide sequences. These sequences exhibit a reverse organization of conserved
      hydrophobic and acidic residues when compared with canonical BH3 sequences, and
      we therefore refer to them as reverse BH3 (rBH3) peptides. Furthermore, studies
      of the rBH3 peptides using NMR spectroscopy, fluorescence polarization
      displacement assays, and alanine scanning data all suggest that they bind to the
      BH3 binding groove of Mcl-1 selectively over Bcl-x(L). A search for proteins
      containing the rBH3 motif has identified a number of interesting Mcl-1 protein
      partners, some of which have previously been associated with apoptosis regulation
      involving Mcl-1. These findings provide insights into the development of more
      specific Mcl-1 antagonists and open the way to the identification of a previously
      unknown family of apoptosis-regulating and Mcl-1 interacting proteins.

PMID- 21953454
TI  - CRM1 protein-mediated regulation of nuclear clusterin (nCLU), an ionizing
      radiation-stimulated, Bax-dependent pro-death factor.
AB  - Expression of the clusterin (CLU) gene results in the synthesis of a conventional
      secretory isoform set (pre- and mature secretory clusterin proteins, psCLU/sCLU),
      as well as another set of intracellular isoforms, appearing in the cytoplasm (pre
      nuclear CLU, pnCLU) and in the nucleus as an ~55-kDa mature nuclear clusterin
      (nCLU) form. These two isoform sets have opposing cell functions: pro-survival
      and pro-death, respectively. Although much is known about the regulation and
      function of sCLU as a pro-survival factor, the regulation and function of
      endogenous nCLU in cell death are relatively unexplored. Here, we show that
      depletion of endogenous nCLU protein using siRNA specific to its truncated mRNA
      increased clonogenic survival of ionizing radiation (IR)-exposed cells. nCLU
      mediated apoptosis was Bax-dependent, and lethality correlated with accumulation
      of mature nCLU protein. nCLU accumulation was regulated by CRM1 because binding
      between CRM1 and nCLU proteins was significantly diminished by leptomycin B
      (LMB), and nuclear levels of nCLU protein were significantly enhanced by LMB and
      IR co-treatment. Moreover, LMB treatment significantly enhanced IR-induced nCLU
      mediated cell death responses. Importantly, bax(-/-) and bax(-/-)/bak(-/-) double
      knock-out cells were resistant to nCLU-mediated cell death, whereas bak(-/-) or
      wild-type bax(+/+)/bak(+/+) cells were hypersensitive. The regulation of nCLU by
      CRM1 nuclear export/import may explain recent clinical results showing that
      highly malignant tumors have lost the ability to accumulate nCLU levels, thereby
      avoiding growth inhibition and cell death.

PMID- 21953455
TI  - Evidence for ATP-dependent structural rearrangement of nuclease catalytic site in
      DNA mismatch repair endonuclease MutL.
AB  - DNA mismatch repair (MMR) greatly contributes to genome integrity via the
      correction of mismatched bases that are mainly generated by replication errors.
      Postreplicative MMR excises a relatively long tract of error-containing single
      stranded DNA. MutL is a widely conserved nicking endonuclease that directs the
      excision reaction to the error-containing strand of the duplex by specifically
      nicking the daughter strand. Because MutL apparently exhibits nonspecific nicking
      endonuclease activity in vitro, the regulatory mechanism of MutL has been argued.
      Recent studies suggest ATP-dependent conformational and functional changes of
      MutL, indicating that the regulatory mechanism involves the ATP binding and
      hydrolysis cycle. In this study, we investigated the effect of ATP binding on the
      structure of MutL. First, a cross-linking experiment confirmed that the N
      terminal ATPase domain physically interacts with the C-terminal endonuclease
      domain. Next, hydrogen/deuterium exchange mass spectrometry clarified that the
      binding of ATP to the N-terminal domain induces local structural changes at the
      catalytic sites of MutL C-terminal domain. Finally, on the basis of the results
      of the hydrogen/deuterium exchange experiment, we successfully identified novel
      regions essential for the endonuclease activity of MutL. The results clearly show
      that ATP modulates the nicking endonuclease activity of MutL via structural
      rearrangements of the catalytic site. In addition, several Lynch syndrome-related
      mutations in human MutL homolog are located in the position corresponding to the
      newly identified catalytic region. Our data contribute toward understanding the
      relationship between mutations in MutL homolog and human disease.

PMID- 21953456
TI  - Mechanism of HIV reverse transcriptase inhibition by zinc: formation of a highly
      stable enzyme-(primer-template) complex with profoundly diminished catalytic
      activity.
AB  - Several physiologically relevant cations including Ca(2+), Mn(2+), and Zn(2+)
      have been shown to inhibit HIV reverse transcriptase (RT), presumably by
      competitively displacing one or more Mg(2+) ions bound to RT. We analyzed the
      effects of Zn(2+) on reverse transcription and compared them to Ca(2+) and
      Mn(2+). Using nucleotide extension efficiency as a readout, Zn(2+) showed
      significant inhibition of reactions with 2 mM Mg(2+), even when present at only
      ~5 MUM. Mn(2+) and Ca(2+) were also inhibitory but at higher concentrations. Both
      Mn(2+) and Zn(2+) (but not Ca(2+)) supported RT incorporation in the absence of
      Mg(2+) with Mn(2+) being much more efficient. The maximum extension rates with
      Zn(2+), Mn(2+), and Mg(2+) were ~0.1, 1, and 3.5 nucleotides per second,
      respectively. Zinc supported optimal RNase H activity at ~25 MUM, similar to the
      optimal for nucleotide addition in the presence of low dNTP concentrations.
      Surprisingly, processivity (average number of nucleotides incorporated in a
      single binding event with enzyme) during reverse transcription was comparable
      with Zn(2+) and Mg(2+), and single RT molecules were able to continue extension
      in the presence of Zn(2+) for several hours on the same template. Consistent with
      this result, the half-life for RT-Zn(2+)-(primer-template) complexes was 220 +/-
      60 min and only 1.7 +/- 1 min with Mg(2+), indicating ~130-fold more stable
      binding with Zn(2+). Essentially, the presence of Zn(2+) promotes the formation
      of a highly stable slowly progressing RT-(primer-template) complex.

PMID- 21953457
TI  - Reduced stimulation of recombinant DNA polymerase gamma and mitochondrial DNA
      (mtDNA) helicase by variants of mitochondrial single-stranded DNA-binding protein
      (mtSSB) correlates with defects in mtDNA replication in animal cells.
AB  - The mitochondrial single-stranded DNA-binding protein (mtSSB) is believed to
      coordinate the functions of DNA polymerase gamma (pol gamma) and the
      mitochondrial DNA (mtDNA) helicase at the mtDNA replication fork. We generated
      five variants of the human mtSSB bearing mutations in amino acid residues
      specific to metazoans that map on the protein surface, removed from the single
      stranded DNA (ssDNA) binding groove. Although the mtSSB variants bound ssDNA with
      only slightly different affinities, they exhibited distinct capacities to
      stimulate the DNA polymerase activity of human pol gamma and the DNA unwinding
      activity of human mtDNA helicase in vitro. Interestingly, we observed that the
      variants with defects in stimulating pol gamma had unaltered capacities to
      stimulate the mtDNA helicase; at the same time, variants showing reduced
      stimulation of the mtDNA helicase activity promoted DNA synthesis by pol gamma
      similarly to the wild-type mtSSB. The overexpression of the equivalent variants
      of Drosophila melanogaster mtSSB in S2 cells in culture caused mtDNA depletion
      under conditions of mitochondrial homeostasis. Furthermore, we observed more
      severe reduction of mtDNA copy number upon expression of these proteins during
      recovery from treatment with ethidium bromide, when mtDNA replication is
      stimulated in vivo. Our findings suggest that mtSSB uses distinct structural
      elements to interact functionally with its mtDNA replisome partners and to
      promote proper mtDNA replication in animal cells.

PMID- 21953458
TI  - Express path analysis identifies a tyrosine kinase Src-centric network regulating
      divergent host responses to Mycobacterium tuberculosis infection.
AB  - Global gene expression profiling has emerged as a major tool in understanding
      complex response patterns of biological systems to perturbations. However, a lack
      of unbiased analytical approaches has restricted the utility of complex
      microarray data to gain novel system level insights. Here we report a strategy,
      express path analysis (EPA), that helps to establish various pathways
      differentially recruited to achieve specific cellular responses under contrasting
      environmental conditions in an unbiased manner. The analysis superimposes
      differentially regulated genes between contrasting environments onto the network
      of functional protein associations followed by a series of iterative enrichments
      and network analysis. To test the utility of the approach, we infected THP1
      macrophage cells with a virulent Mycobacterium tuberculosis strain (H37Rv) or the
      attenuated non-virulent strain H37Ra as contrasting perturbations and generated
      the temporal global expression profiles. EPA of the results provided details of
      response-specific and time-dependent host molecular network perturbations.
      Further analysis identified tyrosine kinase Src as the major regulatory hub
      discriminating the responses between wild-type and attenuated Mtb infection. We
      were then able to verify this novel role of Src experimentally and show that Src
      executes its role through regulating two vital antimicrobial processes of the
      host cells (i.e. autophagy and acidification of phagolysosome). These results
      bear significant potential for developing novel anti-tuberculosis therapy. We
      propose that EPA could prove extremely useful in understanding complex cellular
      responses for a variety of perturbations, including pathogenic infections.

PMID- 21953459
TI  - The Fbw7 tumor suppressor regulates nuclear factor E2-related factor 1
      transcription factor turnover through proteasome-mediated proteolysis.
AB  - Nuclear factor E2-related factor 1 (Nrf1) is a basic leucine zipper transcription
      factor that plays important roles in cellular stress response and development.
      Currently, the mechanism regulating Nrf1 expression is poorly understood. We
      report here that Nrf1 is a short-lived protein that is targeted by F-box protein
      Fbw7, which is the substrate-specifying component of SCF (Skp1-Cul1-Fbox protein
      Rbx1)-type ubiquitin ligase for degradation via the ubiquitin-proteasome pathway.
      We show that Fbw7 directly binds Nrf1 through a Cdc4 phosphodegron and that
      enforced expression of Fbw7 promotes the ubiquitination and degradation of Nrf1.
      Conversely, depletion of endogenous Fbw7 leads to decreased Nrf1 ubiquitination
      and accumulation of Nrf1 protein. Accordingly, expression of Fbw7 leads to down
      regulation of antioxidant response element-driven gene activation, whereas
      disruption of Fbw7-mediated destabilization of Nrf1 leads to increased
      antioxidant response element-driven gene expression. Together, these data
      identify Fbw7 as a regulator of Nrf1 expression and reveal a novel function of
      Fbw7 in cellular stress response.

PMID- 21953460
TI  - Two-component PhoB-PhoR regulatory system and ferric uptake regulator sense
      phosphate and iron to control virulence genes in type III and VI secretion
      systems of Edwardsiella tarda.
AB  - Inorganic phosphate (P(i)) and iron are essential nutrients that are depleted by
      vertebrates as a protective mechanism against bacterial infection. This
      depletion, however, is sensed by some pathogens as a signal to turn on the
      expression of virulence genes. Here, we show that the PhoB-PhoR two-component
      system senses changes in P(i) concentration, whereas the ferric uptake regulator
      (Fur) senses changes in iron concentration in Edwardsiella tarda PPD130/91 to
      regulate the expression of type III and VI secretion systems (T3SS and T6SS)
      through an E. tarda secretion regulator, EsrC. In sensing low P(i) concentration,
      PhoB-PhoR autoregulates and activates the phosphate-specific transport operon,
      pstSCAB-phoU, by binding directly to the Pho box in the promoters of phoB and
      pstS. PhoB also binds with EsrC simultaneously on the promoter of an E. tarda
      virulence protein, evpA, to regulate directly the transcription of genes from
      T6SS. In addition, PhoB requires and interacts with PhoU to activate esrC and
      suppress fur indirectly through unidentified regulators. Fur, on the other hand,
      senses high iron concentration and binds directly to the Fur box in the promoter
      of evpP to inhibit EsrC binding to the same region. In addition, Fur suppresses
      transcription of phoB, pstSCAB-phoU, and esrC indirectly via unidentified
      regulators, suggesting negative cross-talk with the Pho regulon. Physical
      interactions exist between Fur and PhoU and between Fur and EsrC. Our findings
      suggest that T3SS and T6SS may carry out distinct roles in the pathogenicity of
      E. tarda by responding to different environmental factors.

PMID- 21953461
TI  - The transcriptome of a human polar body accurately reflects its sibling oocyte.
AB  - Improved methods are needed to reliably and accurately evaluate oocyte quality
      prior to fertilization and transfer into the woman of human embryos created
      through in vitro fertilization (IVF). All oocytes that are retrieved and matured
      in culture are exposed to sperm with little in the way of evaluating the oocyte
      quality. Furthermore, embryos created through IVF are currently evaluated for
      developmental potential by morphology, a criterion lacking in quantitation and
      accuracy. With the recent successes in oocyte vitrification and storage, clear
      metrics are needed to determine oocyte quality prior to fertilizing. The first
      polar body (PB) is extruded from the oocyte before fertilization and can be
      biopsied without damaging the oocyte. Here, we tested the hypothesis that the PB
      transcriptome is representative of that of the oocyte. Polar body biopsy was
      performed on metaphase II (MII) oocytes followed by single-cell transcriptome
      analysis of the oocyte and its sibling PB. Over 12,700 unique mRNAs and miRNAs
      from the oocyte samples were compared with the 5,431 mRNAs recovered from the
      sibling PBs (5,256 shared mRNAs or 97%, including miRNAs). The results show that
      human PBs reflect the oocyte transcript profile and suggests that mRNA detection
      and quantification through high-throughput quantitative PCR could result in the
      first molecular diagnostic for gene expression in MII oocytes. This could allow
      for both oocyte ranking and embryo preferences in IVF applications.

PMID- 21953462
TI  - MicroRNA-18a enhances the interleukin-6-mediated production of the acute-phase
      proteins fibrinogen and haptoglobin in human hepatocytes.
AB  - The acute-phase response is an inflammatory process triggered mainly by the
      cytokine IL-6. Signaling of IL-6 is transduced by activation of STAT3 (signal
      transducer and activator of transcription 3), which rapidly induces the
      production of acute-phase proteins such as haptoglobin and fibrinogen. Another
      target of the IL-6/STAT3 signal transduction pathway is the microRNA cluster miR
      17/92. Here, we investigated the interplay of miR-17/92 and STAT3 signaling and
      its impact on the acute-phase response in primary human hepatocytes and hepatoma
      (HepG2) cells. Employing a reporter gene system consisting of STAT3-sensitive
      promoter sequences, we show that the miR-17/92 cluster member miR-18a enhanced
      the transcriptional activity of STAT3. IL-6 stimulation experiments in miR-18a
      overexpressing hepatocytes and HepG2 cells revealed an augmented acute-phase
      response indicated by increased expression and secretion of haptoglobin and
      fibrinogen. This effect was due, at least in part, to repression of PIAS3
      (protein inhibitor of activated STAT, 3), a repressor of STAT3 activity, which we
      identified as a novel direct target of miR-18a. Finally, we demonstrate that the
      expression of miR-17/92 in primary hepatocytes and HepG2 cells is modulated by IL
      6. Our data reveal, for the first time, a microRNA-mediated positive feedback
      loop of IL-6 signal transduction leading to an enhanced acute-phase response in
      human hepatocytes.

PMID- 21953463
TI  - The E3 ubiquitin ligase SMAD ubiquitination regulatory factor 2 negatively
      regulates Kruppel-like factor 5 protein.
AB  - The zinc finger transcription factor Kruppel-like factor 5 (KLF5) is regulated
      posttranslationally. We identified SMAD ubiquitination regulatory factor 2
      (SMURF2), an E3 ubiquitin ligase, as an interacting protein of KLF5 by yeast two
      hybrid screen, coimmunoprecipitation, and indirect immunofluorescence studies.
      The SMURF2-interacting domains in KLF5 were mapped to its carboxyl terminus,
      including the PY motif of KLF5 and its zinc finger DNA-binding domain. KLF5
      protein levels were reduced significantly upon overexpression of SMURF2 but not
      catalytically inactive SMURF2-C716A mutant or SMURF1. SMURF2 alone reduced the
      protein stability of KLF5 as shown by cycloheximide chase assay, indicating that
      SMURF2 specifically destabilizes KLF5. In contrast, KLF5(1-165), a KLF5 amino
      terminal construct that lacks the PY motif and DNA binding domain, was not
      degraded by SMURF2. The degradation of KLF5 by SMURF2 was blocked by the
      proteasome inhibitor MG132, and SMURF2 efficiently ubiquitinated both
      overexpressed and endogenous KLF5. In contrast, knocking down SMURF2 by siRNAs
      significantly enhanced KLF5 protein levels, reduced ubiquitination of KLF5, and
      increased the expression of cyclin D1 and PDGF-A, two established KLF5 target
      genes. In consistence, SMURF2, but not the E3 ligase mutant SMURF2-C716A,
      significantly inhibited the transcriptional activity of KLF5, as demonstrated by
      dual luciferase assay using the PDGF-A promoter, and suppressed the ability of
      KLF5 to stimulate cell proliferation as measured by BrdU incorporation. Hence,
      SMURF2 is a novel E3 ubiquitin ligase for KLF5 and negatively regulates KLF5 by
      targeting it for proteasomal degradation.

PMID- 21953464
TI  - Structure-guided inhibitor design for human acetyl-coenzyme A carboxylase by
      interspecies active site conversion.
AB  - Inhibition of acetyl-CoA carboxylases (ACCs), a crucial enzyme for fatty acid
      metabolism, has been shown to promote fatty acid oxidation and reduce body fat in
      animal models. Therefore, ACCs are attractive targets for structure-based
      inhibitor design, particularly the carboxyltransferase (CT) domain, which is the
      primary site for inhibitor interaction. We have cloned, expressed, and purified
      the CT domain of human ACC2 using baculovirus-mediated insect cell expression
      system. However, attempts to crystallize the human ACC2 CT domain have not been
      successful in our hands. Hence, we have been using the available crystal
      structure of yeast CT domain to design human ACC inhibitors. Unfortunately, as
      the selectivity of the lead series has increased against the full-length human
      enzyme, the potency against the yeast enzyme has decreased significantly. This
      loss of potency against the yeast enzyme correlated with a complete lack of
      binding of the human-specific compounds to crystals of the yeast CT domain. Here,
      we address this problem by converting nine key active site residues of the yeast
      CT domain to the corresponding human residues. The resulting humanized yeast ACC
      CT (yCT-H9) protein exhibits biochemical and biophysical properties closer to the
      human CT domain and binding to human specific compounds. We report high
      resolution crystal structures of yCT-H9 complexed with inhibitors that show a
      preference for the human CT domain. These structures offer insights that explain
      the species selectivity of ACC inhibitors and may guide future drug design
      programs.

PMID- 21953465
TI  - A1Ao-ATP synthase of Methanobrevibacter ruminantium couples sodium ions for ATP
      synthesis under physiological conditions.
AB  - An unresolved question in the bioenergetics of methanogenic archaea is how the
      generation of proton-motive and sodium-motive forces during methane production is
      used to synthesize ATP by the membrane-bound A(1)A(o)-ATP synthase, with both
      proton- and sodium-coupled enzymes being reported in methanogens. To address this
      question, we investigated the biochemical characteristics of the A(1)A(o)-ATP
      synthase (MbbrA(1)A(o)) of Methanobrevibacter ruminantium M1, a predominant
      methanogen in the rumen. Growth of M. ruminantium M1 was inhibited by
      protonophores and sodium ionophores, demonstrating that both ion gradients were
      essential for growth. To study the role of these ions in ATP synthesis, the
      ahaHIKECFABD operon encoding the MbbrA(1)A(o) was expressed in Escherichia coli
      strain DK8 (Deltaatp) and purified yielding a 9-subunit protein with an SDS
      stable c oligomer. Analysis of the c subunit amino acid sequence revealed that it
      consisted of four transmembrane helices, and each hairpin displayed a complete
      Na(+)-binding signature made up of identical amino acid residues. The purified
      MbbrA(1)A(o) was stimulated by sodium ions, and Na(+) provided pH-dependent
      protection against inhibition by dicyclohexylcarbodiimide but not tributyltin
      chloride. ATP synthesis in inverted membrane vesicles lacking sodium ions was
      driven by a membrane potential that was sensitive to cyanide m
      chlorophenylhydrazone but not to monensin. ATP synthesis could not be driven by a
      chemical gradient of sodium ions unless a membrane potential was imposed. ATP
      synthesis under these conditions was sensitive to monensin but not cyanide m
      chlorophenylhydrazone. These data suggest that the M. ruminantium M1 A(1)A(o)-ATP
      synthase exhibits all the properties of a sodium-coupled enzyme, but it is also
      able to use protons to drive ATP synthesis under conditions that favor proton
      coupling, such as low pH and low levels of sodium ions.

PMID- 21953466
TI  - Membrane depolarization increases membrane PtdIns(4,5)P2 levels through
      mechanisms involving PKC betaII and PI4 kinase.
AB  - In a previous study, we showed that membrane depolarization induced elevation of
      membrane phosphatidylinositol 4,5-bisphosphates (PtdIns(4,5)P(2), also known as
      PIP(2)) and subsequently increased the KCNQ2/Q3 currents expressed in Xenopus
      oocytes through increased PI4 kinase activity. In this study, the underlying
      mechanism for this depolarization-induced enhancement of PIP(2) synthesis was
      further investigated. Our results indicate that activation of protein kinase C
      (PKC) isozyme betaII was responsible for the enhanced PIP(2) synthesis. We found
      that phorbol-12-myristate, 13-acetate (PMA), an activator of PKC, mimicked the
      effects of the membrane depolarization by increasing KCNQ2/Q3 activity, elevating
      membrane PIP(2) levels and increasing activity of PI4 kinase beta. Furthermore,
      membrane depolarization enhanced PKC activity. The effects of both depolarization
      and PMA were blocked by a PKC inhibitor or PI4 kinase beta RNA interference.
      Further results demonstrate that the depolarization selectively activated the PKC
      betaII isoform and enhanced its interaction with PI4 kinase beta. These results
      reveal that the depolarization-induced elevation of membrane PIP(2) is through
      activation of PKC and the subsequent increased activity of PI4 kinase beta.

PMID- 21953467
TI  - Ubiquitination in the first cytoplasmic loop of MU-opioid receptors reveals a
      hierarchical mechanism of lysosomal down-regulation.
AB  - MU-Type opioid receptors (MORs) are members of the large seven-transmembrane
      receptor family which transduce the effects of both endogenous neuropeptides and
      clinically important opioid drugs. Prolonged activation of MORs promotes their
      proteolytic degradation by endocytic trafficking to lysosomes. This down
      regulation process is known to contribute to homeostatic regulation of cellular
      opioid responsiveness, but mechanisms that mediate and control MOR down
      regulation have not been defined. We show here that lysosomal down-regulation of
      MORs is ESCRT (endosomal sorting complex required for transport)-dependent and
      involves ubiquitin-promoted transfer of internalized MORs from the limiting
      endosome membrane to lumen. We also show that MOR down-regulation measured by
      conventional radioligand binding assay is determined specifically by
      ubiquitination in the first cytoplasmic loop. Surprisingly, we were unable to
      find any role of ubiquitination in determining whether internalized receptors
      recycle or are delivered to lysosomes. Instead, this decision is dictated
      specifically by the MOR C-tail and occurs irrespectively of the presence or
      absence of receptor ubiquitination. Our results support a hierarchical
      organization of discrete ubiquitin-independent and -dependent sorting operations,
      which function non-redundantly in the conserved down-regulation pathway to
      mediate precise endocytic control. Furthermore, they show that this hierarchical
      mechanism discriminates the endocytic regulation of naturally occurring MOR
      isoforms. Moreover, they are the first to reveal, we believe, for any seven
      transmembrane receptor, a functional role of ubiquitination in the first
      cytoplasmic loop.

PMID- 21953468
TI  - Transmembrane gate movements in the type II ATP-binding cassette (ABC) importer
      BtuCD-F during nucleotide cycle.
AB  - ATP-binding cassette (ABC) transporters are ubiquitous integral membrane proteins
      that translocate substrates across cell membranes. The alternating access of
      their transmembrane domains to opposite sides of the membrane powered by the
      closure and reopening of the nucleotide binding domains is proposed to drive the
      translocation events. Despite clear structural similarities, evidence for
      considerable mechanistic diversity starts to accumulate within the importers
      subfamily. We present here a detailed study of the gating mechanism of a type II
      ABC importer, the BtuCD-F vitamin B(12) importer from Escherichia coli,
      elucidated by EPR spectroscopy. Distance changes at key positions in the
      translocation gates in the nucleotide-free, ATP- and ADP-bound conformations of
      the transporter were measured in detergent micelles and liposomes. The
      translocation gates of the BtuCD-F complex undergo conformational changes in line
      with a "two-state" alternating access model. We provide the first direct evidence
      that binding of ATP drives the gates to an inward-facing conformation, in
      contrast to type I importers specific for maltose, molybdate, or methionine.
      Following ATP hydrolysis, the translocation gates restore to an apo-like
      conformation. In the presence of ATP, an excess of vitamin B(12) promotes the
      reopening of the gates toward the periplasm and the dislodgment of BtuF from the
      transporter. The EPR data allow a productive translocation cycle of the vitamin
      B(12) transporter to be modeled.

PMID- 21953469
TI  - The cancer-associated K351N mutation affects the ubiquitination and the
      translocation to mitochondria of p53 protein.
AB  - Stress-induced monoubiquitination of p53 is a crucial event for the nuclear
      cytoplasm-mitochondria trafficking and transcription-independent pro-apoptotic
      functions of p53. Although an intact ubiquitination pathway and a functional
      nuclear export sequence are required for p53 nuclear export, the role of specific
      residues within this region in regulating both processes remains largely unknown.
      Here we characterize the mechanisms accounting for the nuclear accumulation of a
      new point mutation (Lys-351 to Asn) in the nuclear export sequence of p53
      identified in a cisplatin-resistant ovarian carcinoma cell line (A2780 CIS). We
      found that K351N substitution abrogates the monoubiquitination of p53 induced by
      both Mdm2 and MSL2 E3-ligases. As a consequence, cells expressing p53 K351N
      mutant showed defects in cisplatin-induced translocation of p53 to mitochondria,
      Bax oligomerization, and mitochondrial membrane depolarization. These data
      identify K351N as a critical mutation of p53 that contributes to the development
      and maintenance of resistance to cisplatin.

PMID- 21953470
TI  - Supersaturating drug delivery systems: fast is not necessarily good enough.
AB  - An emerging technology subtype that has been adopted by formulators to address
      low-solubility issues is the supersaturating drug delivery system; this system is
      based on the "spring" and "parachute" design elements, which have been applied to
      lipid-based formulations, S(M)EDDS, solid dispersions, nano-based systems, and
      many others. This broad formulation approach attempts to delicately balance the
      need of creating intraluminal drug concentrations in excess of its thermodynamic
      solubility while at the same time providing for sufficient solution stability to
      allow for useful drug absorption. The conundrum created is that the higher the
      extent of supersaturation, the lower the physical stability of the metastable
      solution based on an increased tendency for a solubilized drug to precipitate.
      Traditional dissolution testing is a touchstone of formulation development based
      on the need for useful dissolution rates and drug availability. Dissolution
      testing is likewise important in the development and characterization of enabling
      and supersaturating drug delivery systems; however, their execution and
      interpretation are distinct from that associated with conventional dosage forms.
      The nature of the dissolution assay (sink versus nonsink, apparatus type, and
      rate and extent of supersaturation) can impact the ability to efficiently use the
      dissolution data in the configuration of these enabling formulations.

PMID- 21953471
TI  - Efficacy of monthly oral ibandronate is sustained over 5 years: the MOBILE long
      term extension study.
AB  - The long-term efficacy and safety of once-monthly ibandronate were studied in
      this extension to the 2-year Monthly Oral Ibandronate in Ladies (MOBILE) trial.
      Over 5 years, lumbar spine bone mineral density (BMD) increased from baseline
      with monthly ibandronate 150 mg (8.4%). Long-term monthly ibandronate is
      effective and well tolerated for up to 5 years in women with postmenopausal
      osteoporosis. INTRODUCTION: Once-monthly therapy with ibandronate has been
      studied for up to 5 years in a long-term extension (LTE) to the 2 year MOBILE
      trial. METHODS: This multicenter, double-blind extension study of monthly
      ibandronate involved postmenopausal women who had completed 2 years of the MOBILE
      core study, with >=75% adherence. Patients were reallocated, or were randomized
      from daily therapy, to ibandronate 100 mg monthly or 150 mg monthly for a further
      3 years. RESULTS: A pooled intent-to-treat (ITT) analysis of 344 patients
      receiving monthly ibandronate from the core MOBILE baseline showed increases over
      5 years in lumbar spine BMD (8.2% with 100 mg and 8.4% with 150 mg). Three-year
      data relative to MOBILE LTE baseline in the full ITT population of all 698
      patients randomized or reallocated from MOBILE (including those previously on
      daily treatment) showed, on average, maintenance of proximal femur BMD gains
      achieved in the core 2-year study, with further small gains in lumbar spine BMD.
      In general, maintenance of efficacy was also indicated by markers of bone
      metabolism. CONCLUSIONS: There were no tolerability concerns or new safety
      signals. Monthly treatment with ibandronate 100 and 150 mg is effective and well
      tolerated for up to 5 years in women with postmenopausal osteoporosis.

PMID- 21953472
TI  - A reappraisal of generic bisphosphonates in osteoporosis.
AB  - The competitive price of generic bisphosphonates has had a marked effect on
      practice guidelines, but an increasing body of evidence suggests that they have
      more limited effectiveness than generally assumed. INTRODUCTION: The purpose of
      this study is to review the impact of generic bisphosphonates on effectiveness in
      the treatment of osteoporosis. METHODS: This study is a literature review.
      RESULTS: A substantial body of evidence indicates that many generic formulations
      of alendronate are more poorly tolerated than the proprietary preparations which
      results in significantly poorer adherence and thus effectiveness. Poorer
      effectiveness may result from faster disintegration times of many generics that
      increase the likelihood of adherence of particulate matter to the oesophageal
      mucosa. Unfortunately, market authorisation, based on the bioequivalence of
      generics with a proprietary formulation, does not take into account the potential
      concerns about safety. The poor adherence of many generic products has
      implications for guideline development, cost-effectiveness and impact of
      treatment on the burden of disease. CONCLUSIONS: The impact of generic
      bisphosphonates requires formal testing to re-evaluate their role in the
      management of osteoporosis.

PMID- 21953474
TI  - A meta-analysis of brief high-impact exercises for enhancing bone health in
      premenopausal women.
AB  - A snapshot of current evidence from 6 randomised controlled trials for the
      effects of short bouts of high-impact exercises in 256 women via meta-analysis
      reveals that ample osteogenic response could be realised at the femoral neck and
      trochanter of premenopausal women with rest-inserted bouts of few mechanical bone
      loading cycles. INTRODUCTION: Exercise is an important means of improving bone
      health and preventing osteoporosis. Brief bouts of simple exercises may be useful
      for aiding lifestyle compliance to physical activity. This study aimed to review
      the evidence on the effect of brief, high-impact exercise on bone health among
      premenopausal women. METHODS: A structured and comprehensive search of databases
      was undertaken along with hand searching of key journals and reference lists to
      locate relevant studies published and unpublished up to January 2011. Six
      randomised controlled trials met predetermined inclusion criteria. Brief high
      impact exercises (<30 min) were examined for their effect on bone mineral density
      (BMD) among premenopausal women. Trial quality was assessed using the Effective
      Public Health Practice Project quality assessment tool. Study outcomes for
      analysis, absolute change (grams per square centimetre) or relative change (in
      percent) in BMD at femoral neck, trochanter and lumbar spine were compared by
      calculating standardised mean difference (SMD) using fixed- and random effects
      models. RESULTS: Quality of included trials varied from medium to high on a scale
      of 1 to 3. Brief bouts of exercise led to significant increases in femoral neck
      BMD (SMD = 0.64, 95% confidence interval (CI) = 0.38, 0.90, overall effect Z
      value = 4.84, p = 0.001); a modest increase in trochanteric BMD (SMD = 0.36, 95%
      CI = 0.10, 0.61, Z value = 2.08, p = 0.04) and no increase in spinal BMD (SMD =
      0.04, 95% CI= -0.23, 0.31, Z value = 0.26, p = 0.79). CONCLUSION: Based on the
      meta-analysis, brief high-impact exercise improves BMD at the hip but not at the
      lumbar spine. Effectiveness of this form of exercise as a lifestyle physical
      activity for prevention of osteoporosis should be explored in larger populations.

PMID- 21953475
TI  - Cost-effectiveness of the Concord Minimal Trauma Fracture Liaison service, a
      prospective, controlled fracture prevention study.
AB  - We evaluated the cost-effectiveness of a fracture liaison service prospectively
      designed to have a parallel control group treated by standard care. The clinical
      effectiveness of this service was associated with an incremental cost
      effectiveness ratio versus standard care of Australian dollars (AUD) 17,291 per
      quality-adjusted life year (QALY) gained. INTRODUCTION: Osteoporotic fractures
      are a major burden for national health services. The risk of re-fracture
      following an osteoporotic fracture is particularly high. In a study unique in
      prospectively having a control group treated by standard care, we recently
      demonstrated that a Minimal Trauma Fracture Liaison (MTFL) service significantly
      reduces the risk of re-fracture by 80%. Since the service involves greater use of
      resources, we have now evaluated whether it is cost-effective. METHODS: A Markov
      model was developed that incorporated fracture probabilities and resource
      utilization data (expressed in AUD) obtained directly from the 4-year MTFL
      service clinical study. Resource utilization, local cost and mortality data and
      fracture-related health utility data were used to calculate QALYs with the MTFL
      service and standard care. Main outcome measures were: additional costs of the
      MTFL service over standard care, the financial savings achieved through reduced
      fractures and changes in QALYs associated with reduced fractures calculated over
      a 10-year simulation period. Costs and QALYs were discounted at 5% annually.
      Sensitivity analyses quantified the effects of different assumptions of
      effectiveness and resource utilization associated with the MTFL service. RESULTS:
      The MTFL service improved QALYs by 0.089 years and led to increased costs of AUD
      1,486 per patient versus standard care over the 10-year simulation period. The
      incremental cost-effectiveness ratio versus standard care was AUD 17,291 per QALY
      gained. Results were robust under all plausible assumptions. CONCLUSIONS: The
      MTFL service is a cost-effective intervention to reduce recurrent osteoporotic
      fractures.

PMID- 21953476
TI  - Association of N-terminal pro-brain natriuretic peptide with cardiac disease, but
      not with vascular disease, in systemic lupus erythematosus.

PMID- 21953477
TI  - Stevens-Johnson Syndrome induced by masitinib.

PMID- 21953478
TI  - Exclusively intradural exposure and clip reconstruction in complex paraclinoid
      aneurysms.
AB  - BACKGROUND: The management of complex paraclinoid aneurysms is still challenging.
      In this article we describe our approach to paraclinoid aneurysms, which has
      evolved over several years, using an exclusively intradural approach. METHOD: All
      procedures are done under continuous electrophysiological monitoring. A standard
      pterional approach is used to access the paraclinoid region exclusively
      intraduraly. After optic nerve unroofing and tailored clinoidectomy, the aneurysm
      neck is visualized and clipped using the tandem clipping technique and suction
      decompression if necessary. Aneurysm occlusion is verified using intraoperative
      ICG angiography and postoperative 3D DSA. CONCLUSION: The exclusively intradural
      approach to complex paraclinoid aneurysms with tailored clinoidectomy offers an
      excellent surgical corridor for the treatment of these challenging lesions.

PMID- 21953479
TI  - Multifocal choroid plexus papillomas: case report.
AB  - Choroid plexus papillomas (CPP) are rare tumors of the central nervous system,
      usually occurring in the ventricular system. Apart from spinal drop metastases,
      CPPs are generally unique tumors. In this report, the authors present two
      exceptional adult cases involving multiple benign CPPs located in both intra- and
      extraventricular locations. The tumors were located in the fourth ventricle and
      Meckel's cave in one case and the cerebellopontine angle, the frontotemporal
      region and the fourth ventricle in the other. A review of the literature revealed
      that these two cases represent the first reported occurrences of multiple choroid
      plexus papillomas involving Meckel's cave and frontotemporal intraparenchymal
      locations.

PMID- 21953480
TI  - [Experiences with chronic central serous chorioretinopathy treated with half-dose
      photodynamic therapy and verteporfin].
AB  - BACKGROUND: Chronic central serous chorioretinopathy (CSR) is an idiopathic,
      often self-limiting disease usually occurring in younger patients. A
      characteristic sign of CSR is a serous detachment of the neurosensory retina.
      Prognosis with regard to visual acuity is generally good. The disease is chronic
      or recurrent in up to 30% of cases. There is a risk for the development of
      secondary choroidal neovascularization. Therapeutic options include
      photocoagulation or photodynamic therapy (PDT) with verteporfin. In recent years
      there have been several approaches aiming to minimize the side-effects of PDT and
      the treatment protocols were designated half-dose, reduced fluence or low fluence
      PDT. PATIENTS AND METHODS: A total of 7 eyes from 6 male patients with CSR were
      analyzed retrospectively. Before half-dose PDT and at the end of follow-up best
      corrected visual acuity and retinal thickness were measured by spectral domain
      optical coherence tomography. RESULTS: The mean age of the patients was 40.7 +/-
      10.3 years, 5 eyes were treated with a single session of half-dose PDT (25 J /
      cm(2)), 1 with 2 PDTs and 1 with a total of 3 PDTs. Mean follow-up was 79.8 +/-
      104.5 months. Mean visual acuity (Snellen) before PDT was 0.4 +/- 0.2 and 0.4 +/-
      0.3 after PDT (p = 0.49). During the observation period the mean retinal
      thickness (RT) decreased from 479 MUm +/- 233 to 242 MUm +/- 60 (p = 0.08).
      CONCLUSIONS: Half-dose PDT is a safe option for patients with long-standing CSR.
      All patients showed a decrease of retinal thickness, 6 eyes showed a total
      resolution of subretinal fluid and 5 eyes also showed functional improvement.

PMID- 21953481
TI  - Unexpected pancytopenia following treatment of acute lymphoblastic leukemia.

PMID- 21953482
TI  - Human puberty: salivary melatonin profiles in constant conditions.
AB  - This analysis examined the relative contributions of sex, age, body mass index
      (BMI), and puberty (Tanner) stage on salivary melatonin amplitude. Sixty-nine
      children and adolescents (30 females; 9.6-17.8 years) were examined for Tanner
      stage. Serial salivary melatonin samples were collected in controlled conditions,
      from which these melatonin amplitude measures were derived: area under the curve
      (AUC) and maximum value (MAX). AUC declined with advancing Tanner stage. This
      melatonin decline was similar between boys and girls, but girls secreted more
      melatonin compared to boys. Tanner stage and sex explained AUC variability, but
      age and BMI did not; similar results emerged for MAX. These results indicate that
      puberty stage may either mediate the decline of melatonin, or the decrease in
      melatonin amplitude may be an indicator of pubertal progression. These findings
      also indicate that the melatonin decline during puberty is not entirely accounted
      for by body mass or by age.

PMID- 21953483
TI  - Simulating response of N2O emissions to fertiliser N application and climatic
      variability from a rain-fed and wheat-cropped soil in Western Australia.
AB  - BACKGROUND: Besides land management and soil properties, nitrous oxide (N(2)O)
      emissions from the soil may be responsive to climatic variation. In this study
      the Water and Nitrogen Management Model (WNMM) was calibrated and validated to
      simulate N(2)O emissions from a rain-fed and wheat-cropped system on a sandy
      duplex soil at Cunderdin, Western Australia, from May 2005 to May 2007, then it
      was deployed to simulate N(2)O emissions for seven scenarios of fertiliser N
      application under various climatic conditions (1970-2006). RESULTS: The WNMM
      satisfactorily simulated crop growth, soil water content and mineral N contents
      of the surface soil (0-10 cm), soil temperatures at depths and N(2)O emissions
      from the soil compared with field observations in two fertiliser treatments
      during calibration and validation. About 70% of total N(2)O emissions were
      estimated as nitrification-induced. The scenario analysis indicated that the WNMM
      simulated annual N(2)O emissions for this rain-fed and wheat-cropped system were
      significantly correlated with annual average minimum air temperature (r = 0.21),
      annual pan evaporation (r = 0.20) and fertiliser N application rate (r = 0.80).
      Both annual rainfall and wheat yield had weak and negative correlations with
      annual N(2)O emissions. Multiple linear regression models for estimating annual
      N(2)O emissions were developed to account for the impacts of climatic variation
      (including temperature and rainfall), fertiliser N application and crop yield for
      this rain-fed and wheat-cropped system in Western Australia, which explained 64
      74% of yearly variations of the WNMM-estimated annual N(2) O emissions.
      CONCLUSION: The WNMM was tested and capable of simulating N(2) O emissions from
      the rain-fed and wheat-cropped system. The inclusion of climatic variables as
      predictors in multiple linear regression models improved their accuracy in
      predicting inter-annual N(2)O emissions.

PMID- 21953484
TI  - A wide repertoire of miRNA binding sites: prediction and functional implications.
AB  - MOTIVATION: Over the past decade, deciphering the roles of microRNAs (miRNAs) has
      relied heavily upon the identification of their targets. Most of the targets that
      were computationally and experimentally characterized were evolutionarily
      conserved 'seed' targets, containing a perfect 6-8 nt match between the miRNA
      5(')-region and the messenger RNA (mRNA). Gradually, it has become evident that
      other types of miRNA binding can confer target regulation, but their
      characterization has been lagging behind. RESULTS: Here, we complement the
      putative evolutionarily-conserved seed-containing targets by a wide repertoire of
      putative targets exhibiting a variety of miRNA binding patterns, predicted by our
      algorithm RepTar. These include non-conserved sites, 'seed' binding sites with
      G:U-wobbles within the seed, '3(') compensatory' sites and 'centered' sites.
      Apart from the centered sites, we demonstrate the functionality of these sites
      and characterize the target profile of a miRNA by the types of binding sites
      predicted in its target 3(') UTRs. We find that different miRNAs have individual
      target profiles, with some more inclined to seed binding and others more inclined
      to binding through 3(') compensatory sites. This diversity in targeting patterns
      is also evident within several miRNA families (defined by common seed sequences),
      leading to divergence in the target sets of members of the same family. The
      prediction of non-conventional miRNA targets is also beneficial in the search for
      targets of the non-conserved viral miRNAs. Analyzing the cellular targets of
      viral miRNAs, we show that viral miRNAs use various binding patterns to exploit
      cellular miRNA binding sites and suggest roles for these targets in virus-host
      interactions.

PMID- 21953485
TI  - Incidence of deepening of the upper eyelid sulcus after switching from
      latanoprost to bimatoprost.
AB  - PURPOSE: To investigate the incidence of deepening of the upper eyelid sulcus
      (DUES) after use of bimatoprost in Japanese glaucoma patients. METHODS: Twenty
      five open-angle glaucoma Japanese patients treated with latanoprost in both eyes
      for 6 months or longer and needing further intraocular pressure (IOP) reduction
      were enrolled prospectively. Latanoprost was switched to bimatoprost, and the
      patients were observed at 1, 3, and 6 months. The patients were queried for the
      presence of DUES at every visit. Sex, refraction, and IOP were evaluated as
      related factors. The photographs of the eyes and forehead taken at each of the
      four visits were randomly displayed and judged for the presence of DUES with
      unanimous confirmation by three examiners. RESULTS: One month after the switch to
      bimatoprost, 44% (11/25) of the patients had DUES, including three with
      unilateral DUES. At 3 and 6 months, 60% (15/25) of the patients had DUES. The
      incidence was significantly higher in older patients and nonmyopic eyes (P <
      0.01), but not related to sex or IOP reduction. Finally, 53.3% (8/15) of the
      patients objectively judged to have DUES noticed the presence of DUES by
      themselves. Only one patient dropped out of the study because of DUES (after 3
      months). CONCLUSION: DUES is an often-observed side effect of bimatoprost topical
      treatment in Japanese glaucoma patients.

PMID- 21953486
TI  - Detection of ICP0 protein in tear fluid of individuals with active herpetic
      epithelial keratitis.
AB  - PURPOSE: Infected cell protein 0 (ICP0) has been detected in the tear fluid of
      rabbits with herpetic keratitis. Here, we investigated whether ICP0 of herpes
      simplex virus 1 is detectable in the tear fluid of patients with herpetic
      epithelial keratitis. METHODS: Seven patients with herpetic epithelial keratitis
      (age range, 51-76 years) and 11 healthy volunteers (age range, 48-85 years) were
      enrolled in the study. Tear fluid was collected with the use of Schirmer test
      strips and subjected to immunoblot analysis with antibodies to ICP0. RESULTS:
      ICP0 was not detected in the tear fluid of the healthy controls, whereas it was
      detected in 4 of the 7 patients with herpetic keratitis. The tear fluid of the 4
      ICP0-positive patients was collected within 3 days of the onset of keratitis,
      whereas that of the ICP0-negative patients was obtained at least 7 days after
      disease onset. CONCLUSIONS: ICP0 was detected in the tear fluid of patients in
      the early phase of herpetic epithelial keratitis, but not in that of patients in
      the later stages of the disease nor in that of the healthy controls. ICP0
      expression may thus be dependent on the disease phase.

PMID- 21953488
TI  - Is bitter better? The benefits of chocolate for the cardiovascular system.

PMID- 21953487
TI  - Beyond genome-wide association studies: new strategies for identifying genetic
      determinants of hypertension.
AB  - Genetic linkage and association methods have long been the most important tools
      for gene identification in humans. These approaches can either be hypothesis
      based (i.e., candidate-gene studies) or hypothesis-free (i.e., genome-wide
      studies). The first part of this review offers an overview of the latest
      successes in gene finding for blood pressure (BP) and essential hypertension
      using these DNA sequence-based discovery techniques. We further emphasize the
      importance of post-genome-wide association study (post-GWAS) analysis, which aims
      to prioritize genetic variants for functional follow-up. Whole-genome next
      generation sequencing will eventually be necessary to provide a more
      comprehensive picture of all DNA variants affecting BP and hypertension. The
      second part of this review discusses promising novel approaches that move beyond
      the DNA sequence and aim to discover BP genes that are differentially regulated
      by epigenetic mechanisms, including microRNAs, histone modification, and
      methylation.

PMID- 21953489
TI  - Behavioral, neurochemical and histological alterations promoted by bilateral
      intranigral rotenone administration: a new approach for an old neurotoxin.
AB  - Rotenone exposure in rodents provides an interesting model for studying
      mechanisms of toxin-induced dopaminergic neuronal injury. However, several
      aspects remain unclear regarding the effects and the accuracy of rotenone as an
      animal model of Parkinson's disease (PD). In order to counteract these
      limitations, this study characterized a precise neurotoxin-delivery strategy
      employing the bilateral intranigral administration protocol of rotenone as a
      reliable model of PD. We performed bilateral intranigral injections of rotenone
      (12 MUg) and subsequent general activity (1, 10, 20, and 30 days after rotenone)
      and cognitive (7, 8, 15, and 30 days after rotenone) evaluations followed by
      neurochemical and immunohistochemical tests. We have observed that rotenone was
      able to produce a remarkable reduction on the percentage of tyrosine hydroxylase
      immunoreactive neurons (about 60%) within the substantia nigra pars compacta.
      Dopamine (DA) was severely depleted at 30 days after rotenone administration,
      similarly to its metabolites. In addition, an increase in DA turnover was
      detected at the same time-point. In parallel, striatal serotonin and its
      metabolite were found to be increased 30 days after the neurotoxic insult,
      without apparent modification in the serotonin turnover. Besides, motor behavior
      was impaired, mainly 1 day after rotenone. Furthermore, learning and memory
      processes were severely disrupted in different time-points, particularly at the
      training and test session (30 days). We now provide further evidence of a time
      dependent neurodegeneration associated to cognitive impairment after the single
      bilateral intranigral administration of rotenone. Thus, it is proposed that the
      current rotenone protocol provides an improvement regarding the existing rotenone
      models of PD.

PMID- 21953490
TI  - Technical note: estimating sex using cervical canine odontometrics: a test using
      a known sex sample.
AB  - The size of the permanent human canine tooth is one of the few sexually dimorphic
      features to be present in childhood and as such offers the opportunity to assist
      in the identification of sex in remains where no other appropriate criteria
      exist, such as in subadults. However, canine odontometrics are often associated
      with high levels of interobserver error and can be difficult to access if
      dentition is in situ. Additionally, appropriate points of measurement can be
      difficult to identify if the tooth is worn. Alternate measurements of the
      cervical canine diameters have been proposed as solutions to these issues, but
      the utility of these measurements in estimating sex has not been conclusively
      demonstrated. This study uses the buccolingual and mesiodistal cervical diameter
      of the canines from a known-sex sample from St. Bride's Church, London and a
      partially known-sex sample from the Old Church, Chelsea, London to classify
      individuals as male or female. A discriminant function classification using these
      diameters successfully identifies sex in 93.8% of the known-sex assemblage and
      95% of the partially osteologically estimated sex assemblage. It is suggested
      that cervical canine diameters are highly repeatable measurements with low
      interobserver error, can be obtained on worn and in situ teeth, and provide as
      good or better guidance on estimating sex in human remains as standard maximal
      diameters.

PMID- 21953491
TI  - Hepatocyte polarization is essential for the productive entry of the hepatitis B
      virus.
AB  - Human hepatitis B virus (HBV) is characterized by a high species specificity and
      a distinct liver tropism. Within the liver, HBV replication occurs in
      differentiated and polarized hepatocytes. Accordingly, the in vitro HBV infection
      of primary human hepatocytes (PHHs) and the human hepatoma cell line, HepaRG, is
      restricted to differentiated, hepatocyte-like cells. Though preparations of PHH
      contain up to 100% hepatic cells, cultures of differentiated HepaRG cells are a
      mixture of hepatocyte-like and biliary-like epithelial cells. We used PHH and
      HepaRG cells and compared the influence of virus inoculation dose, cell
      differentiation, and polarization on productive HBV infection. At multiplicities
      of genome equivalents (mge) >8,000, almost 100% of PHHs could be infected. In
      contrast, only a subset of HepaRG cells stained positive for HBcAg at comparable
      or even higher mge. Infection predominantly occurred at the edges of islands of
      hepatocyte-like HepaRG cells. This indicates a limited accessibility of the HBV
      receptor, possibly as a result of its polar sorting. Multidrug resistance protein
      2 (MRP2), a marker selectively transported to the apical (i.e., canalicular) cell
      membrane, revealed two polarization phenotypes of HepaRG cells. HBV infection
      within the islands of hepatocyte-like HepaRG cells preferentially occurred in
      cells that resemble PHH, exhibiting canalicular structures. However, disruption
      of cell-cell junctions allowed the additional infection of cells that do not
      display a PHH-like polarization. CONCLUSION: HBV enters hepatocytes via the
      basolateral membrane. This model, at least partially, explains the difference of
      PHH and HepaRG cells in infection efficacy, provides insights into natural HBV
      infection, and establishes a basis for optimization of the HepaRG infection
      system.

PMID- 21953492
TI  - Synthesis and in-vivo evaluation of carbonyl-amide linkage based new
      benzimidazole derivatives.
AB  - In search of pharmacologically active potent compounds, a series of carbonyl
      amide linkage based new benzimidazole derivatives were synthesized from acid,
      aldehydes and isocyanide at ambient temperature via Passerini reaction. All the
      compounds synthesized were screened for their potential anti-inflammatory,
      antidiabetic and anticonvulsant properties. The results revealed that compounds
      2i and 2j were found to be the most potent anti-inflammatory agents, while
      compounds 2a, 2c, 2e, 2f, 2i and 2j showed increased antidiabetic activity than
      the reference drugs and 2a, 2g, 2h, 2i and 2j were found to be the main
      structural requirement for maintaining anticonvulsant activity.

PMID- 21953493
TI  - A new strategy for meta-analysis of continuous covariates in observational
      studies.
AB  - When several studies are available, a meta-analytic assessment of the effect of a
      risk or prognostic factor on an outcome is often required. We propose a new
      strategy, requiring individual participant data, to provide a summary estimate of
      the functional relationship between a continuous covariate and the outcome in a
      regression model, adjusting for confounding factors. Our procedure comprises
      three steps. First, we determine a confounder model. Ideally, the latter should
      include the same variables across studies, but this may be impossible. Next, we
      estimate the functional form for the continuous variable of interest in each
      study, adjusted for the confounder model. Finally, we combine the individual
      functions by weighted averaging to obtain a summary estimate of the function.
      Fractional polynomial methodology and pointwise weighted averaging of functions
      are the key components. In contrast to a pooled analysis, our approach can
      reflect more variability between functions from different studies and more
      flexibility with respect to confounders. We illustrate the procedure by using
      data from breast cancer patients in the Surveillance, Epidemiology, and End
      Results Program database, where we consider data from nine individual registries
      as separate studies. We estimate the functional forms for the number of positive
      lymph nodes and age. The former is an example where a strong prognostic effect
      has long been recognized, whereas the prognostic effect of the latter is weak or
      even controversial. We further discuss some general issues that are found in meta
      analyses of observational studies.

PMID- 21953494
TI  - Effect of HMGB1 silencing on cell proliferation, invasion and apoptosis of MGC
      803 gastric cancer cells.
AB  - High-mobility group box 1 (HMGB1) is a multifunctional protein with intranuclear
      and extracellular functions. Although HMGB1 is overexpressed in approximately 85%
      of gastric cancers, the role of HMGB1 in gastric cancer biology remains unclear.
      In this study, we investigate the effect of downregulation of HMGB1 on the
      biological behavior of gastric cancer cells. MGC-803 gastric cancer cells were
      transduced with HMGB1-specific RNAi lentiviral vectors. Real-time polymerase
      chain reaction and Western blot analysis of HMGB1 mRNA and protein, respectively,
      validated the silencing effects. HMGB1-specific silencing significantly decreased
      cell proliferation. The impact on proliferation was observed at the cell cycle
      level--the number of cells in the G0/G1 phase increased, whereas that in S and
      G2/M phases decreased. Cell cycle changes were accompanied by decreases in cyclin
      D1 expression. Furthermore, HMGB1 silencing sensitized cells to apoptosis that
      was induced by oxaliplatin and mediated by the caspase-3 pathway. Finally,
      silencing of HMGB1 expression significantly reduced cellular metastatic ability
      and MMP-9 expression in MGC-803 cells. In summary, HMGB1 not only plays an
      essential role in the proliferation and invasion of MGC-803 cells but also
      represents a potential target for the therapeutic intervention of gastric cancer.

PMID- 21953495
TI  - Failures in cognitive-behavior therapy for children.
AB  - This article discusses treatment failures in child therapy, specifically
      cognitive-behavioral therapy (CBT) for anxiety and its disorders. The theoretical
      foundations and principles of CBT are discussed first, followed by a summary of
      the treatment outcome literature. Also discussed is how treatment failure is
      defined and gauged in CBT, as well as factors implicated in treatment failure. A
      case illustration highlights these factors, which resulted in the child not
      advancing positively in treatment. The article concludes with key practice
      recommendations.

PMID- 21953496
TI  - The role of melanoma tumor-derived nitric oxide in the tumor inflammatory
      microenvironment: its impact on the chemokine expression profile, including
      suppression of CXCL10.
AB  - Melanoma appears to be heterogeneous in terms of its molecular biology, etiology
      and epidemiology. We previously reported that the expression of inducible nitric
      oxide synthase (iNOS) in melanoma tumor cells is strongly correlated with poor
      patient survival. Therefore, we hypothesized that nitric oxide (NO) produced by
      iNOS promotes the melanoma inflammatory tumor microenvironment associated with
      poor outcome. To understand the role of NO and iNOS in the melanoma inflammatory
      tumor microenvironment, polymerase chain reaction arrays of inflammatory and
      autoimmunity genes were performed on a series of stage III melanoma lymph node
      metastasis samples to compare the gene expression profiles of iNOS-expressing and
      nonexpressing tumor samples. The results indicate that expression of CXC
      chemokine ligand 10 (CXCL10) was inversely correlated with iNOS expression, and
      the high CXCL10-expressing cases had more favorable prognoses than the low CXCL10
      expressing cases. Functional studies revealed that treating iNOS-negative/CXCL10
      positive melanoma cell lines with a NO donor suppressed the expression of CXCL10.
      Furthermore, scavenging NO from iNOS-expressing cell lines significantly affected
      the chemokine expression profile. Culture supernatants from NO scavenger-treated
      melanoma cells promoted the migration of plasmacytoid dendritic cells, which was
      diminished when the cells were treated with a CXCL10-neutralizing antibody.
      CXCL10 has been reported to be an antitumorigenic chemokine. Our study suggests
      that the production of NO by iNOS inhibits the expression of CXCL10 in melanoma
      cells and leads to a protumorigenic tumor microenvironment. Inhibiting NO induces
      an antitumorigenic environment, and thus, iNOS should be considered to be an
      important therapeutic target in melanoma.

PMID- 21953497
TI  - A phase II, multicenter, open-label study evaluating dosing and preliminary
      safety and efficacy of canakinumab in systemic juvenile idiopathic arthritis with
      active systemic features.
AB  - OBJECTIVE: To assess dosing, preliminary safety, and efficacy of canakinumab, a
      fully human anti-interleukin-1beta (anti-IL-1beta) antibody, in children with
      systemic juvenile idiopathic arthritis (JIA) and active systemic features.
      METHODS: In this phase II, multicenter, open-label, dosage-escalation study,
      children with systemic JIA who were >=4 years of age, had fever, and were
      receiving <=0.4 mg/kg/day of corticosteroids were administered a single
      subcutaneous dose of canakinumab, 0.5-9 mg/kg of body weight, and were redosed
      upon relapse. Response to treatment was assessed according to an adaptation of
      the American College of Rheumatology (ACR) pediatric criteria for improvement.
      RESULTS: A total of 23 children ages 4-19 years with active disease were
      enrolled. Of these, 1 patient was excluded from analysis, and 3 of the reenrolled
      patients were included twice in the efficacy analysis. By day 15 of the first
      treatment cycle, 15 of 25 patients (60%) had achieved an adapted ACR Pediatric 50
      response, with 4 of them achieving inactive disease status. Response was
      sustained over time, with 11 of 13 patients able to maintain their response
      throughout the study. In 8 of the 11 responders who had been receiving steroids
      at baseline, the steroid dosage was decreased from a mean of 0.38 mg/kg/day to
      0.13 mg/kg/day over the first 5 months, and 4 of them were able to discontinue
      steroids. At a dose of 4 mg/kg of canakinumab given subcutaneously every 4 weeks,
      the median percentage of patients predicted to relapse within 4 weeks was
      estimated to be 6% (95% confidence interval 1-21). Therapy was generally well
      tolerated and few patients experienced injection-site reactions. CONCLUSION:
      Canakinumab has a promising preliminary safety and efficacy profile in this
      limited cohort. Based on the findings of this trial, further studies in a larger
      population of children with systemic JIA are warranted.

PMID- 21953498
TI  - Community health workers and medicaid managed care in New Mexico.
AB  - We describe the impact of community health workers (CHWs) providing community
      based support services to enrollees who are high consumers of health resources in
      a Medicaid managed care system. We conducted a retrospective study on a sample of
      448 enrollees who were assigned to field-based CHWs in 11 of New Mexico's 33
      counties. The CHWs provided patients education, advocacy and social support for a
      period up to 6 months. Data was collected on services provided, and community
      resources accessed. Utilization and payments in the emergency department,
      inpatient service, non-narcotic and narcotic prescriptions as well as outpatient
      primary care and specialty care were collected on each patient for a 6 month
      period before, for 6 months during and for 6 months after the intervention. For
      comparison, data was collected on another group of 448 enrollees who were also
      high consumers of health resources but who did not receive CHW intervention. For
      all measures, there was a significant reduction in both numbers of claims and
      payments after the community health worker intervention. Costs also declined in
      the non-CHW group on all measures, but to a more modest degree, with a greater
      reduction than in the CHW group in use of ambulatory services. The incorporation
      of field-based, community health workers as part of Medicaid managed care to
      provide supportive services to high resource-consuming enrollees can improve
      access to preventive and social services and may reduce resource utilization and
      cost.

PMID- 21953499
TI  - Enhanced immune response against pertussis toxoid by IgA-loaded chitosan-dextran
      sulfate nanoparticles.
AB  - The objective of the present study was to evaluate immunological activities of
      chitosan-dextran sulfate (CS-DS) nanoparticle formulation of pertussis toxoid
      (PTXd) and its combination with a potential immunological adjuvant,
      immunoglobulin A (IgA). CS-DS nanoparticles were prepared using a complex
      coacervation (polyelectrolyte complexation) technique. CS-DS nanoparticle
      formulations with size and zeta potential in a range of 300-350 nm and +40-+55
      mV, respectively, were obtained. An entrapment efficiency of more than 90% was
      obtained for pertussis toxin and IgA in CS-DS nanoparticles. All loaded
      nanoparticle formulations showed less than 20% of release within 24 h in in vitro
      release studies. The immunological evaluation of developed formulations in female
      Balb/c mice groups showed that the CS-DS nanoparticles formulations induced
      significantly higher serum IgG and IgG1 titers (p < 0.05) as compared with
      conventional alum-adjuvanted PTXd formulation administered by subcutaneous route.
      This study indicated the potential of CS-DS nanoparticles to be a simple and
      effective particulate delivery system with in-built immunological adjuvant
      property for acellular protein antigens. The study also revealed the potential
      important role of IgA-loaded CS-DS nanoparticles as a novel immunological
      adjuvant for vaccine delivery.

PMID- 21953500
TI  - CREMalpha suppresses spleen tyrosine kinase expression in normal but not systemic
      lupus erythematosus T cells.
AB  - OBJECTIVE: T cells from patients with systemic lupus erythematosus (SLE) display
      increased amounts of spleen tyrosine kinase (Syk), which is involved in the
      aberrant CD3/T cell receptor-mediated signaling process, and increased amounts of
      CREMalpha, which suppresses the production of interleukin-2. Syk expression can
      be suppressed by CREMalpha. This study was undertaken to investigate why
      CREMalpha fails to suppress Syk expression in SLE T cells. METHODS: CREMalpha was
      overexpressed in healthy T cells by transfection with CREMalpha expression
      vector, and Syk expression and phosphorylation were measured. A newly identified
      cAMP response element (CRE) site on the SYK promoter was characterized by
      chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assay.
      The CREMalpha-mediated repression of Syk expression was further evaluated by
      analyzing SYK promoter activity. T cells from SLE patients and healthy
      individuals were subjected to ChIP to evaluate CREMalpha binding and histone H3
      acetylation. RESULTS: Increased CREMalpha levels suppressed Syk expression by
      direct binding to a CRE site of the SYK promoter in T cells from healthy
      individuals but failed to do so in T cells from SLE patients. The failure of
      CREMalpha to suppress Syk expression in SLE T cells was due to weaker binding to
      the CRE site of the SYK promoter compared to healthy T cells because the promoter
      site is hypoacetylated in SLE T cells and therefore of limited access to
      transcription factors. CONCLUSION: Our findings indicate that epigenetic
      alteration of the SYK promoter in SLE T cells results in the inability of the
      transcriptional repressor CREMalpha to bind and suppress the expression of Syk,
      resulting in aberrant T cell signaling.

PMID- 21953502
TI  - Cetuximab pharmacokinetics influences progression-free survival of metastatic
      colorectal cancer patients.
AB  - PURPOSE: An ancillary phase II study was conducted to study interindividual
      variability in cetuximab pharmacokinetics and its influence on progression-free
      survival (PFS) in metastatic colorectal cancer patients cotreated with irinotecan
      and 5-fluorouracil. EXPERIMENTAL DESIGN: Ninety-six patients received cetuximab
      as an infusion loading dose of 400 mg/m(2) followed by weekly infusions of 250
      mg/m(2). Doses of irinotecan and 5-fluorouracil were adjusted individually.
      Cetuximab concentrations were measured by ELISA. Compartmental pharmacokinetic
      parameters were estimated by a population approach, and PFS was analyzed using a
      Cox model. RESULTS: Cetuximab pharmacokinetics was best described using a two
      compartment model with both first-order and saturable (zero-order) elimination.
      Estimated pharmacokinetic parameters (% standard error) were as follows: central
      volume of distribution V(1) = 2.96 L (4%), peripheral volume of distribution V(2)
      = 4.65 L (6%), elimination clearance CL = 0.497 L/d (4%), distribution clearance
      Q = 0.836 L/d (8%), and zero-order elimination rate k(0) = 8.71 mg/d (10%). Body
      surface area influenced V(1), V(2), and k(0). Pretreatment serum albumin
      influenced CL. Risk of disease progression decreased with cetuximab global
      clearance (cumulative dose/cumulative area under the concentration versus time
      curve; P = 0.00016). Median PFS of patients with a cetuximab residual
      concentration on day 14 below median value was 3.3 months as compared with 7.8
      months for the other patients (P = 0.004). CONCLUSIONS: Cetuximab
      pharmacokinetics in colorectal cancer patients can be described using a model
      combining linear and nonlinear elimination rates. PFS is influenced by global
      clearance of cetuximab, a parameter that can be estimated using cetuximab
      residual concentration on day 14.

PMID- 21953501
TI  - Beyond VEGF: inhibition of the fibroblast growth factor pathway and
      antiangiogenesis.
AB  - Fibroblast growth factor (FGF) signaling regulates cell proliferation,
      differentiation, survival, angiogenesis, and wound healing. Compelling evidence
      for deregulated FGF signaling in tumorigenesis continues to emerge, and a growing
      body of research suggests that FGF may also play an integral role in the
      resistance to anti-VEGF therapy. Although agents targeting FGF signaling are
      early in development, the potential to target both the VEGF and FGF pathways may
      translate into improvements in the clinical care of cancer patients.

PMID- 21953503
TI  - Reduced miR-128 in breast tumor-initiating cells induces chemotherapeutic
      resistance via Bmi-1 and ABCC5.
AB  - PURPOSE: Tumor-initiating cells are resistant to chemotherapy, but how microRNAs
      play a role in regulating drug resistance of breast tumor-initiating cells (BT
      IC) needs to be clarified. EXPERIMENTAL DESIGN: Lentivirus-mediated miR-128
      transduction was done in BT-ICs, enriched by mammosphere cultures or CD44(+)CD24(
      ) fluorescence-activated cell sorting. Apoptosis and DNA damage were determined
      upon treatment with doxorubicin. Expression of miR-128 in breast cancer tissues
      was examined by in situ hybridization and correlated with breast tumor response
      to neoadjuvant chemotherapy and patient survival. RESULTS: MiR-128 was
      significantly reduced in chemoresistant BT-ICs enriched from breast cancer cell
      lines and primary breast tumors (P < 0.01), accompanied by an overexpression of
      Bmi-1 and ABCC5, which were identified as targets of miR-128. Ectopic expression
      of miR-128 reduced the protein levels of Bmi-1 and ABCC5 in BT-ICs, along with
      decreased cell viability (P < 0.001) and increased apoptosis (P < 0.001) and DNA
      damage (P < 0.001) in the presence of doxorubicin. Reduced miR-128 expression in
      breast tumor tissues was associated with chemotherapeutic resistance (P < 0.001)
      and poor survival of breast cancer patients (P < 0.05; n = 57). CONCLUSIONS:
      Reduction in miR-128 leading to Bmi-1 and ABCC5 overexpression is a stem cell
      like feature of BT-ICs, which contributes to chemotherapeutic resistance in
      breast cancers. Ectopic expression of miR-128 sensitizes BT-ICs to the
      proapoptotic and DNA-damaging effects of doxorubicin, indicating therapeutic
      potential.

PMID- 21953504
TI  - Spatial and temporal variations of total and methylmercury concentrations in
      plankton from a mercury-contaminated and eutrophic reservoir in Guizhou Province,
      China.
AB  - Total mercury (THg) and methylmercury (MeHg) concentrations in four size
      fractions of plankton from three sampling stations in the Hg-contaminated and
      eutrophic Baihua Reservoir, Guizhou, China, were investigated for
      biomagnification and trophic transfer of Hg at different sites with various
      proximity to the major point sources of nutrients and metals. Total Hg
      concentrations in plankton of the various size fractions varied from 49 to 5,504
      ng g(-1) and MeHg concentrations ranged from 3 to 101 ng g(-1). The percentage of
      Hg as MeHg varied from 0.16 to 70%. Total Hg and MeHg concentrations in plankton
      samples differed among the three sampling stations with different proximities
      from the major point sources. The plankton from the site closest to the dam
      contained the highest concentrations of MeHg. The successive increase of the
      ratios of MeHg to Hg from seston to macroplankton at all sites indicated that
      biomagnification is occurring along the plankton food web. However,
      biomagnification factors (BMF) for MeHg were low (1.5-2.0) between trophic
      levels. Concentrations of THg in seston decreased with an increase of chlorophyll
      concentrations, suggesting a significant dilution effect by the algae bloom for
      Hg. Eutrophication dilution may be a reason for lower MeHg accumulation by the
      four size classes of plankton in this Hg-contaminated reservoir.

PMID- 21953505
TI  - Left atrial dilatation and ST-T changes predict cardiovascular outcome in chronic
      hemodialysis patients.
AB  - The left atrium (LA) is afterload-sensitive, meaning that it responds to changes
      in left ventricular diastolic pressure, and left atrial volumetric remodeling has
      been reported. We prospectively examined the effects of LA enlargement and ST-T
      changes on cardiovascular outcome of chronic hemodialysis (HD) patients.
      Echocardiography was performed twice, a mean interval of 2.1 +/- 0.4 years apart,
      and LA size, left ventricular mass index (LVMI), and other indices were
      evaluated. The prognostic value of ST-T changes and LA dilatation for
      cardiovascular events was investigated in a cohort of 112 HD patients. The LVDd,
      interventricular septum thickness, fractional shortening, and LVMI values were
      higher in the HD patients with ST-T changes and LA dilatation at the second
      echocardiography. Moreover, LV hypertrophy (LVH) and new cardiovascular events
      were more common in HD patients with both ST-T changes and LA dilatation (p =
      0.0127). Interdialysis weight gain, presence of ST-T changes and LA dilatation,
      and use of calcium channel blockers were significantly associated with LVH, and
      the odds ratios were 1.740, 2.870, and 0.304, respectively. Over a mean follow-up
      period of 2.1 +/- 0.4 years, 27 patients experienced new cardiovascular event. A
      Cox proportional hazard analysis revealed that complication of coronary artery
      diseases, the presence of ST-T changes and LA dilatation, and serum albumin
      levels were significantly associated with incident cardiovascular events, and the
      hazard ratios were 3.898, 5.182, and 0.185 (1 g/dl per year increase),
      respectively. In a Kaplan-Meier analysis, incident cardiovascular events were
      significantly less common in HD patients without ST-T changes and LA dilatation
      than those with (p < 0.0001), 50% event-free period was about 2 years in HD
      patients with ST-T changes and LA dilatation. In conclusion, ST-T changes and LA
      dilatation predict the cardiovascular outcome of chronic HD patients. Detecting
      ST-T changes on ECG and LA dilatation is useful for monitoring cardiovascular
      risk in chronic HD patients.

PMID- 21953506
TI  - Microbial diversity during Rotary Drum and Windrow Pile composting.
AB  - This study investigates the prevailing microbial communities during the
      composting of vegetable waste, cattle manure and saw dust, in a household (250 l)
      batch scale Rotary Drum composter and Windrow Pile. Physico-chemical parameters
      were analyzed to study the organic matter transformations. Total organic matter
      reduced from 63.8% to 36.2% in rotary drum and 39.6% in windrow pile composting.
      The C/N ratio decreased from 26.52 to 8.89 and 14.33 in rotary drum and windrow
      pile composting. The indigenous population of total heterotrophic bacteria
      decreased in rotary drum and windrow pile composting after 20 days. However,
      total fungal load initially increased within initial 4 days, then subsequently
      reduced in final composts. The average number of fecal coliforms and fecal
      Streptococci showed decrement with time, in both composting systems. Escherichia
      coli and Salmonella species number deduced during the study. Composting cycle
      started with Gram positive rods but ended up with the dominance of Gram negative
      bacilli shaped bacteria. Transformation of organic compounds during the
      biodegradation of organic waste, difference in the utilization of nutrients
      (organic matter) by the different group of microbes and high temperature could be
      cited as a possible reason of the above changes. Scanning electron microscopy has
      been used to obtain the surface structures of the cultured mycoflora. Results of
      the study revealed that higher diversity of microbes prevailed in rotary drum as
      compared to windrow pile, yielding more stable and pathogenic free compost in
      lesser period of composting.

PMID- 21953507
TI  - Effects of foliar and fruit addition of sodium selenate on selenium accumulation
      and fruit quality.
AB  - BACKGROUND: We investigated the effects of the foliar and fruit application of
      sodium selenate on selenium (Se) accumulation, fruit growth and ripening in peach
      and pear. Trials were conducted in two growing seasons. In 2008 selenate was
      applied at a rate of 0.1 and 1.0 mg Se L-1 to the leaves of peach. In 2009
      selenate was applied at a rate of 1 mg Se L-1 via foliar (LT) or fruit (FT)
      application to peach and pear. RESULTS: The foliar addition of selenate to peach
      resulted in an increase in Se concentration both in leaves and fruit. The higher
      Se content in fruit resulted in an increase in flesh firmness and a decrease in
      soluble solid content. LT significantly increased the Se content in the leaves
      and fruit of peach and pear, and leaves showed the highest Se concentrations. FT
      increased the fruit Se concentration in both crops, and it was more effective
      than LT in increasing Se content. After storage, flesh firmness decreased in all
      treatments, but it was significantly higher in FT compared to LT and control
      samples. CONCLUSION: Foliar and fruit selenium spraying appeared effective in
      increasing the Se content of fruit in peach and pear. The enhanced Se
      concentration affected the shelf life of fruit, delaying the reduction in flesh
      firmness and fruit ripening, thus positively affecting fruit storage.

PMID- 21953508
TI  - High levels of antenatal maternal anxiety are associated with altered cognitive
      control in five-year-old children.
AB  - This longitudinal prospective study examined the relation between maternal
      anxiety during pregnancy and specific aspects of children's cognitive functioning
      at age five. Antenatal maternal state-anxiety was measured around the 16th week
      of pregnancy. Children's neurocognitive functioning was examined using a simple
      reaction time (RT) task, and a choice RT task. Multiple regression analyses in
      the total sample (N = 922) showed that antenatal anxiety was positively related
      to children's intra-individual variability in RT in the simple task. In a
      subsample (n = 100) of women with state-anxiety scores above the 90th percentile,
      antenatal anxiety was positively associated with mean RT and intra-individual
      variability in RT in the incompatible trials of the choice RT task. In addition,
      in this subsample of highly anxious mothers we found a significant positive
      association in boys but not in girls, between prenatal maternal anxiety and intra
      individual variability in RT in the simple task.

PMID- 21953509
TI  - Weekly exercise does not improve fatigue levels in Parkinson's disease.
AB  - BACKGROUND: Fatigue is one of the most disabling non-motor symptoms for people
      with Parkinson's disease. Exercise may modify fatigue. This study examines
      prescribed exercise effects on physical activity levels, well-being, and fatigue
      in Parkinson's disease. METHODS: In this single-blinded trial, participants were
      randomly assigned to either a 12 week community exercise program or control
      group. Primary outcome measures were fatigue (Fatigue Severity Scale) and
      physical activity. RESULTS: Thirty-nine people with Parkinson's disease were
      included: 20 in exercise and 19 in control. Sixty-five percent of the study group
      were fatigued (n = 24, mean 4.02, SD 1.48). Increased fatigue was associated with
      lower mobility and activity (P < .05). Individuals participated in a mean of 15
      (SD 10) exercise sessions with no significant change in fatigue, mobility, well
      being, or physical activity after exercise (P >= .05). CONCLUSION: Participation
      in weekly exercise did not improve fatigue in people with Parkinson's Disease.

PMID- 21953510
TI  - Clinical outcome and monitoring of minimal residual disease in patients with
      acute lymphoblastic leukemia expressing the MLL/ENL fusion gene.
AB  - We analyzed 12 MLL/ENL positive ALL patients consecutively diagnosed between 1999
      and 2009. The MLL/ENL fusion was identified in 4/150 (2.6%), 8/993 (0.8%), and
      0/70 of pediatric, adult, and elderly patients, respectively. Eight patients had
      a WBC count >50 * 10(9) /L. Ten cases had an evaluable immunophenotyping. A B or
      T precursor ALL occurred in 7 and 3 patients, respectively. Eleven/12 patients
      (92%) achieved CR. At 48 months, overall survival and event-free survival rates
      were 73.3% and 67%, respectively. At CR, a parallel RT-PCR evaluation of the
      MLL/ENL expression was available in 5 cases. Of these latter, 2 tested MLL/ENL
      negative and 3 positive. The minimal residual disease molecular monitoring showed
      that MLL/ENL status did not correlate with outcome. In fact, all the 2 PCR
      negative and 1 of the 3 PCR-positive cases relapsed. Further, a MLL/ENL
      expression, not preceding a relapse, was detected several times during the follow
      up of five long-survivors. In conclusion, also in adults, the MLL/ENL fusion
      identifies a rare leukemic entity with a favorable prognosis. The observed
      inconsistency between the clinical cure and the presence of detectable MLL/ENL
      transcript suggests the existence of a MLL/ENL-expressing "preleukemia" stem
      cells, similar to what demonstrated for the AML1/ETO-positive leukemia setting.

PMID- 21953512
TI  - An unusual neurological syndrome of crawling gait, dystonia, pyramidal signs, and
      limited speech.
AB  - BACKGROUND: The purpose of the study was to identify and molecularly characterize
      a neurological syndrome in a consanguineous Pakistani family. METHODS: Five
      patients, their 2 siblings, and their parents were clinically examined. DNA from
      all 7 siblings was genotyped with Affymetrix SNP arrays and sequencing of
      selected candidate genes. RESULTS: An unusual neurological syndrome of crawling
      gait, predominant leg dystonia, pyramidal signs, microcephaly, and suspected
      deafness segregated in the family. Three patients ambulated on hands and knees,
      either by hopping and crossing their legs, or by dragging the legs behind them.
      Two patients have acquired the ability to walk bipedally with a dystonic gait.
      Unexpectedly, no chromosomal region was homozygous in patients only. Under
      different disease models, we localized 7 chromosomal regions in the genome common
      to all patients. No pathogenic mutations were identified in selected candidate
      genes or the mitochondrial genome. CONCLUSION: We describe an unusual movement
      disorder syndrome reminiscent of but distinct from Uner Tan syndrome.

PMID- 21953511
TI  - Immunobiology of Merkel cell carcinoma: implications for immunotherapy of a
      polyomavirus-associated cancer.
AB  - Merkel cell carcinoma (MCC) is an aggressive skin malignancy with a high
      mortality rate and an increasing incidence. The recent discovery of Merkel cell
      polyomavirus has revolutionized our understanding of MCC pathogenesis. Viral
      oncoproteins appear to play a critical role in tumor progression and are
      expressed in the majority of MCC tumors. Virus-specific humoral and cellular
      immune responses are detectable in MCC patients and are linked to the natural
      history of the disease. Despite persistent expression of immunogenic viral
      proteins, however, MCC tumors are able to evade the immune system. Understanding
      of the mechanisms of immune evasion employed by MCC tumors is rapidly increasing
      and offers opportunities for development of rational immune therapies to improve
      patient outcomes. Here we review recent discoveries in MCC with a special focus
      on the pathogenic role of Merkel cell polyomavirus and the immunobiology of this
      virus-associated disease.

PMID- 21953513
TI  - Effect of recombinant erythropoietin on ischemia-reperfusion-induced apoptosis in
      rat liver.
AB  - Ischemia-reperfusion (I/R) cannot be avoided in liver transplantation procedures,
      and apoptosis is a central mechanism of cell death after liver reperfusion.
      Protective effect of recombinant erythropoietin (rhEPO) on liver apoptosis has
      not been clearly investigated. This work investigated intraportal (IP) rhEPO
      protective effect in a rat model of hepatic I/R-induced apoptosis and its
      appropriated time and dose of administration. Eight groups were included (n =
      10/group): sham-operated, I/R (45 min ischemia and 2 h reperfusion),
      preconditioned rhEPO I/R (24 h or 30 min before ischemia), and postconditioned
      rhEPO I/R (before reperfusion) using two different rhEPO doses (1,000 and 5,000
      IU/kg). When compared with the sham-operated group, the I/R group showed
      significant increase of serum levels of aspartate and alanine aminotransferases
      (AST, ALT), hepatic caspase-9 activity(894.99 +/- 176.90 relative fluorescence
      units (RFU)/mg/min versus 458.48 +/- 82.96 RFU/mg/min), and Fas ligand (FasL)
      expression, histopathological damages, and significant decrease in the
      antiapoptotic Bcl-xL/apoptotic Bax ratio(0.38 +/- 0.21 versus 3.35 +/- 0.77)
      rhEPO-improved ALT and AST but failed to reduce FasL expression in all groups
      compared with the I/R group. Thirty minutes and 24 h preconditioning with rhEPO
      (1,000 IU/kg) increased Bcl-xL/Bax ratio and reduced caspase-9 activity, and the
      same effect was observed when higher dose was given 24 h before ischemia.
      Preconditioning was more effective than postconditioning in improving caspase-9
      activity, and no dose-dependent effect was observed. In conclusion, single IP
      rhEPO injection 30 min before ischemia has an advantage over rhEPO
      postconditioning in improving post-hepatic I/R-induced apoptosis with no
      additional time- and dose-dependent effects which may provide potentially useful
      guide in liver transplantation procedures.

PMID- 21953514
TI  - Regulation of hepatic lipin-1 by ethanol: role of AMP-activated protein
      kinase/sterol regulatory element-binding protein 1 signaling in mice.
AB  - Lipin-1 is a protein that exhibits dual functions as a phosphatidic acid
      phosphohydrolase enzyme in the triglyceride synthesis pathways and a
      transcriptional coregulator. Our previous studies have shown that ethanol causes
      fatty liver by activation of sterol regulatory element-binding protein 1 (SREBP
      1) and inhibition of hepatic AMP-activated protein kinase (AMPK) in mice. Here,
      we tested the hypothesis that AMPK-SREBP-1 signaling may be involved in ethanol
      mediated up-regulation of lipin-1 gene expression. The effects of ethanol on
      lipin-1 were investigated in cultured hepatic cells and in the livers of chronic
      ethanol-fed mice. Ethanol exposure robustly induced activity of a mouse lipin-1
      promoter, promoted cytoplasmic localization of lipin-1, and caused excess lipid
      accumulation, both in cultured hepatic cells and in mouse livers. Mechanistic
      studies showed that ethanol-mediated induction of lipin-1 gene expression was
      inhibited by a known activator of AMPK or overexpression of a constitutively
      active form of AMPK. Importantly, overexpression of the processed nuclear form of
      SREBP-1c abolished the ability of 5-aminoimidazole-4-carboxamide ribonucleoside
      to suppress ethanol-mediated induction of lipin-1 gene-expression level.
      Chromatin immunoprecipitation assays further revealed that ethanol exposure
      significantly increased the association of acetylated histone H3 at lysine 9 with
      the SRE-containing region in the promoter of the lipin-1 gene. CONCLUSION: In
      conclusion, ethanol-induced up-regulation of lipin-1 gene expression is mediated
      through inhibition of AMPK and activation of SREBP-1.

PMID- 21953516
TI  - Non-inferiority test and confidence interval for the difference in correlated
      proportions in diagnostic procedures based on multiple raters.
AB  - The efficacy of diagnostic procedures is generally evaluated on the basis of the
      results from multiple raters. However, there are few adequate methods of
      performing non-inferiority tests with confidence intervals to compare the
      accuracies (sensitivities or specificities) when multiple raters are considered.
      We propose new statistical methods for comparing the accuracies of two diagnostic
      procedures in a non-inferiority trial, on the basis of the results from multiple
      independent raters who are also independent of the study centers. We consider a
      study design in which each patient is subjected to two diagnostic procedures and
      all images are read by all raters. By assuming a multinomial distribution for
      matched-pair categorical data arising from the study design, we derive a score
      based full menu, that is, a non-inferiority test, confidence interval and sample
      size formula, for inference of the difference in correlated proportions between
      the two diagnostic procedures. We conduct Monte Carlo simulation studies to
      examine the validity of the proposed methods, which showed that the proposed test
      has a size closer to the nominal significance level than a Wald-type test and
      that the proposed confidence interval has better empirical coverage probability
      than a Wald-type confidence interval. We illustrate the proposed methods with
      data from a study of diagnostic procedures for the diagnosis of oesophageal
      carcinoma infiltrating the tracheobronchial tree.

PMID- 21953515
TI  - Administration of memantine and imipramine alters mitochondrial respiratory chain
      and creatine kinase activities in rat brain.
AB  - Several studies have appointed for a role of glutamatergic system and/or
      mitochondrial function in major depression. In the present study, we evaluated
      the creatine kinase and mitochondrial respiratory chain activities after acute
      and chronic treatments with memantine (N-methyl-D: -aspartate receptor
      antagonist) and imipramine (tricyclic antidepressant) in rats. To this aim, rats
      were acutely or chronically treated for 14 days once a day with saline, memantine
      (5, 10 and 20 mg/kg) and imipramine (10, 20 and 30 mg/kg). After acute or chronic
      treatments, we evaluated mitochondrial respiratory chain complexes (I, II, II-III
      and IV) and creatine kinase activities in prefrontal cortex, hippocampus and
      striatum. Our results showed that both acute and chronic treatments with
      memantine or imipramine altered respiratory chain complexes and creatine kinase
      activities in rat brain; however, these alterations were different with relation
      to protocols (acute or chronic), complex, dose and brain area. Finally, these
      findings further support the hypothesis that the effects of imipramine and
      memantine could be involve mitochondrial function modulation.

PMID- 21953517
TI  - Activity patterns in the Sahara Desert: an interpretation based on cross
      sectional geometric properties.
AB  - The Garamantian civilization flourished in modern Fezzan, Libya, between 900 BC
      and 500 AD, during which the aridification of the Sahara was well established.
      Study of the archaeological remains suggests a population successful at coping
      with a harsh environment of high and fluctuating temperatures and reduced water
      and food resources. This study explores the activity patterns of the Garamantes
      by means of cross-sectional geometric properties. Long bone diaphyseal shape and
      rigidity are compared between the Garamantes and populations from Egypt and
      Sudan, namely from the sites of Kerma, el-Badari, and Jebel Moya, to determine
      whether the Garamantian daily activities were more strenuous than those of other
      North African populations. Moreover, sexual dimorphism and bilateral asymmetry
      are assessed at an intra- and inter-population level. The inter-population
      comparisons showed the Garamantes not to be more robust than the comparative
      populations, suggesting that the daily Garamantian activities necessary for
      survival in the Sahara Desert did not generally impose greater loads than those
      of other North African populations. Sexual dimorphism and bilateral asymmetry in
      almost all geometric properties of the long limbs were comparatively low among
      the Garamantes. Only the lower limbs were significantly stronger among males than
      females, possibly due to higher levels of mobility associated with herding. The
      lack of systematic bilateral asymmetry in cross-sectional geometric properties
      may relate to the involvement of the population in bilaterally intensive
      activities or the lack of regular repetition of unilateral activities.

PMID- 21953518
TI  - Running wheel exercise ameliorates methamphetamine-induced damage to dopamine and
      serotonin terminals.
AB  - Repeated administration of methamphetamine (mAMPH) to rodents in a single-day
      "binge" produces long-lasting damage to dopaminergic and serotonergic terminals.
      Because previous research has demonstrated that physical activity can ameliorate
      nigrostriatal injury, this study investigated whether voluntary exercise in rats
      can alter the monoaminergic damage resulting from a neurotoxic mAMPH binge. Adult
      male rats were allowed constant access to running wheels or kept in nonwheel
      cages for three weeks, then given a binge dosing regimen of mAMPH or saline. The
      rats were returned to their original environments for three additional weeks post
      mAMPH. [(125) I]RTI-55 binding and autoradiography was used to quantify dopamine
      transporters (DAT), and radioimmunocytochemistry was used to quantify striatal
      tyrosine hydroxylase (TH). Binge mAMPH treatment significantly reduced striatal
      DAT and TH in a regionally specific pattern; with greatest effects in ventral
      caudate-putamen (CP) and relative sparing of the nucleus accumbens septi (NAc).
      The effects of mAMPH on striatal DAT and TH were ameliorated in the running,
      compared to the sedentary, animals. Also, mAMPH was found to reduce [(125) I]RTI
      55 binding to serotonin transporters (SERT) in frontoparietal cortex, and this
      too was significantly attenuated by exercise. Additional correlational analyses
      showed that the post-mAMPH running of individual animals predicted the
      amelioration of striatal DAT and TH as well as frontoparietal SERT. Overall,
      voluntary exercise significantly diminished mAMPH-induced forebrain monoaminergic
      damage. The significant correlations between post-mAMPH exercise and markers of
      monoaminergic terminal integrity provide novel evidence that voluntary exercise
      may exert beneficial effects on behavior in recovering mAMPH addicts.

PMID- 21953520
TI  - Hierarchy of risk of childhood-onset rheumatoid arthritis conferred by HLA-DRB1
      alleles encoding the shared epitope.
AB  - OBJECTIVE: Associations between shared epitope (SE)-encoding HLA-DRB1 alleles and
      rheumatoid arthritis (RA) are well established. However, only a limited number of
      studies have investigated these alleles in patients with childhood-onset RA,
      which is defined as rheumatoid factor- and/or anti-citrullinated protein antibody
      positive juvenile idiopathic arthritis. The aims of this study were to
      investigate the largest cohort of patients with childhood-onset RA for
      association with SE alleles and to determine whether there is a hierarchy of risk
      based on the amino acid sequence of the SE. METHODS: High-resolution HLA-DRB1
      genotypes were obtained for 204 patients with childhood-onset RA and 373 healthy
      control subjects. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were
      calculated for different SE-encoding HLA-DRB1 alleles. In addition, genotype ORs
      were calculated for combinations of SE alleles classified into S(2) , S(3P) , or
      L alleles, based on amino acid sequences in position 70-74 of the DRbeta1 chain,
      as proposed by Tezenas du Montcel et al. RESULTS: We confirmed associations
      between HLA-DRB1 SE alleles and childhood-onset RA (76% of patients carried 1 or
      2 SE alleles compared with 46% of control subjects; OR 3.81, 95% CI 2.4-6.0, P <
      1 * 10(-7) ). We also observed associations between individual SE alleles (HLA
      DRB1*0101, *0401, *0404, *0405, *0408, and *1001) and childhood-onset RA.
      Genotype-specific risk estimates suggested a hierarchy of risk, with the highest
      risk among individuals heterozygous for S(2) /S(3P)  (OR 22.3, 95% CI 9.9-50.5, P
      < 0.0001). CONCLUSION: We confirm the association between SE-encoding HLA-DRB1
      alleles and susceptibility to childhood-onset RA. The excess risk conferred by
      carriage of the combination of S(2)  and S(3P)  risk alleles suggests that
      children with DRbeta1 chains containing the KRAA and QRRAA or RRRAA sequences are
      especially susceptible to RA.

PMID- 21953521
TI  - Dynamics and diversity of phosphate mineralizing bacteria in the coral reefs of
      Gulf of Mannar.
AB  - Phosphatase Producing Bacteria (PPB) and Inorganic Phosphate Solubilizing
      Bacteria (IPSB) are important to reef nutrition. These microbes and phosphate
      concentration play a significant role in the productivity of coral reef
      ecosystems. A study was conducted in Gulf of Mannar coral reef ecosystem to
      understand the diversity of these groups of bacteria and their competence in
      mineralizing the phosphate. The PPB isolates were identified under six genera
      i.e. Bacillus, Pseudomonas, Micrococcus, Vibrio, Arthrobacter and Brevibacterium.
      Likewise, the IPSB isolates were also identified that belong to six genera i.e.
      Bacillus, Arthrobacter, Pseudomonas, Flavobacterium, Flavomonas and Micrococcus.
      Among the PPB and IPSB strains, Bacillus represented more number of species than
      others. PPB exhibited maximum activity between pH 8 and 9 and the lowest was at
      pH 6. Among the phosphatase producers Bacillus cereus (546) showed maximum
      activity (0.333 mmol/l P) at pH 8. In general, the phosphatase activity in most
      of the Bacillus species varied with reference to different pH. The species
      Bacillus megaterium (573) showed highest phosphate solubilizing activity (0.906
      mmol/l P) by producing 2-ketogluconic acid. The production of organic acids and
      phosphatase enzymes by these bacterial groups are responsible for the conversion
      of insoluble inorganic and organic phosphates into soluble forms which are
      available for the reef organisms.

PMID- 21953522
TI  - Indications and relative renal function for paediatric nephrectomy over a 20-year
      period.
AB  - BACKGROUND: The indications for partial or total nephrectomy for urological
      reasons are not clearly documented in the paediatric surgical literature and
      there are only a limited number of publications on this subject. PURPOSE: In
      order to clarify the situation in our centre, we reviewed our own indications for
      nephrectomy over a 20-year period. METHODS: Medical records of patients who
      underwent nephrectomy for urological and oncological causes between May 1990 and
      October 2010 at our centre were retrospectively reviewed. Indications for
      nephrectomy were noted. Renal function was noted for urological cases. RESULTS: A
      total of 357 nephrectomies were undertaken; out of these, 241 cases were for
      urological causes and 116 for oncological reasons. The majority of total
      nephrectomies were performed for multicystic dysplastic kidneys, reflux
      nephropathy, pelvi-ureteric junction obstruction and dysplasia. Eighty-seven
      patients exhibited no function at the time of nephrectomy. Of the remainder, 17
      had <5% function, 18 had 5-10% function, 5 had 10-15% function and 2 patients had
      15-20% function. CONCLUSIONS: This is the largest series of nephrectomies in the
      paediatric surgery literature to date. The majority of nephrectomies were
      undertaken for urological conditions with relative renal function of <10% and
      could not have been usefully preserved in situ. We suggest that kidneys with >10%
      function should not be routinely removed.

PMID- 21953523
TI  - Effectiveness of ultrasonography in the postoperative follow-up of pediatric
      patients undergoing ureteroscopic stone manipulation.
AB  - OBJECTIVES: To evaluate the effectiveness of ultrasonography and to determine
      whether ionizing radiation is necessary in the postoperative follow-up of
      children undergoing ureteroscopy. METHODS: We reviewed the charts of 49 children
      who underwent 51 ureteroscopic procedures for ureteral calculi. Renal ultrasound
      and intravenous urography were performed in all patients at 3 months after
      surgery for postoperative evaluation. RESULTS: In three cases, stones migrated to
      the kidney. Retrograde intrarenal surgery was performed in two patients and one
      patient required shockwave lithotripsy to become stone-free. Fourty-six children
      were completely stone-free and 3 had residual fragments on plain film in the
      postoperative 3 month. The sensitivity, specificity, negative and positive
      predictive values of ultrasonography for detecting hydronephrosis were 85.7, 100,
      97.7 and 100%, respectively. Two patients under observation and three patients
      under medical expulsive therapy had resolution of hydronephrosis on follow-up.
      One patient required ureteroscopy for residual obstructing fragments.
      CONCLUSIONS: Ultrasonography has limited accuracy for detecting residual ureteral
      stones, but it is a highly specific and reasonably sensitive test for detecting
      hydronephrosis. A combination of ultrasonography and plain film is a safe and
      effective imaging procedure in postoperative follow-up of children undergoing
      ureteroscopy.

PMID- 21953524
TI  - Plasma cotinine levels and pancreatic cancer in the EPIC cohort study.
AB  - Smoking is an established risk factor for pancreatic cancer, previously
      investigated by the means of questionnaires. Using cotinine as a biomarker for
      tobacco exposure allows more accurate quantitative analyses to be performed. This
      study on pancreatic cancer, nested within the European Prospective Investigation
      into Cancer and Nutrition (EPIC cohort), included 146 cases and 146 matched
      controls. Using liquid chromatography-mass spectrometry, plasma cotinine levels
      were analyzed on average 8.0 years before cancer onset (5-95% range: 2.8-12.0
      years). The relation between plasma cotinine levels and pancreatic cancer was
      analyzed with conditional logistic regression for different levels of cotinine in
      a population of never and current smokers. This was also done for the self
      reported number of smoked cigarettes per day at baseline. Every increase of 350
      nmol/L of plasma cotinine was found to significantly elevate risk of pancreatic
      cancer [odds ratio (OR): 1.33, 95% confidence interval (CI): 1.11-1.60]. People
      with a cotinine level over 1187.8 nmol/L, a level comparable to smoking 17
      cigarettes per day, have an elevated risk of pancreatic cancer, compared to
      people with cotinine levels below 55 nmol/L (OR: 3.66, 95% CI: 1.44-9.26). The
      results for self-reported smoking at baseline also show an increased risk of
      pancreatic cancer from cigarette smoking based on questionnaire information.
      People who smoke more than 30 cigarettes per day showed the highest risk compared
      to never smokers (OR: 4.15, 95% CI: 1.02-16.42). This study is the first to show
      that plasma cotinine levels are strongly related to pancreatic cancer.

PMID- 21953525
TI  - Fe3+-immobilized nanoparticle-modified capillary for capillary electrophoretic
      separation of phosphoproteins and non-phosphoproteins.
AB  - A fused-silica capillary modified with Fe3+-immobilized magnetic nanoparticles
      (Fe3+-IMAN) has been investigated for the capillary electrophoretic (CE)
      separation of phosphoproteins and non-phosphoproteins. The Fe3+-IMAN capillary
      was achieved by covalently immobilising epoxy-based magnetic silica nanoparticles
      (160 nm) on the prederivatized 3-aminopropyl-trimethoxysilane (APTMS) fused
      silica capillary (75 MUm id), followed by disodium iminodiacetate and Fe3+. The
      buildup process was examined by measuring the streaming potentials of the bare
      capillary, APTMS capillary, epoxy-based nanoparticle capillary and Fe3+-IMAN
      capillary by varying the buffer pH. An inverted fluorescence microscope was used
      to determine the surface features of the Fe3+-IMAN capillary derivatized with
      morin. Further experimental results confirmed that Fe3+-IMAN bonded on the inner
      wall of the APTMS capillary could provide sufficient solute-bonded phase
      interactions to allow for the CE separation of phosphoproteins and non
      phosphoproteins at concentration levels down to 50 MUg/mL. The highest number of
      theoretical plates obtained was about 233,000/m, and the relative standard
      deviation (RSD) for migration times was <2.57% for eight consecutive runs,
      respectively. Additionally, the Fe3+-IMAN modifing method was also applied to the
      analyses of bovine milk proteins. With simplicity, high resolving power, and high
      repeatability, the proposed method has shown great potential for
      phosphoproteomics applications.

PMID- 21953526
TI  - Effects of desipramine on the antioxidant status in rat tissues at carrageenan
      induced paw inflammation.
AB  - The pathogenesis of many diseases and different pathological conditions,
      including inflammation, is associated with excess production of reactive oxygen
      species (ROS). The present study aimed to investigate the effects of the
      antidepressant desipramine (DES) on carrageenan (CG)-induced inflammation, as
      well as on the endogenous levels of cell enzyme and non-enzyme antioxidants in
      rat liver and spleen, 4 and 24 h after CG injection. The intra-plantar CG
      injection into the right hind paw resulted in a time-dependent increase in the
      paw volume; the maximum of CG-induced edema peak was in 2-4 h. A single DES dose
      of 20 mg . kg(-1) , administered 30 min before CG, had no effect on paw edema,
      whereas the higher drug dose used (50 mg . kg(-1) ) suppressed the edematous
      response to CG. The latter drug dose protected CG-induced decrease of glutathione
      (non-enzyme antioxidant) in the liver; it did not affect CG-unchanged activities
      of superoxide dismutase, glutathione peroxidase (enzyme antioxidants) and glucose
      6-phosphate dehydrogenase (enzyme, important for the activity of glutathione
      conjugated antioxidant enzymes) in both liver and spleen. The drug showed an
      efficient antioxidant capacity in ROS-generating chemical systems; it was higher
      than that of fluoxetine (another type of antidepressant). The present results
      suggest that the good antioxidant activity of DES might contribute to its
      beneficial effects in liver injuries.

PMID- 21953527
TI  - Reproduction of aquatic hyphomycetes at low concentrations of Ca2+, Zn2+, Cu2+,
      and Cd2+.
AB  - Maple leaf disks were conditioned in a stream for three weeks and then aerated
      for 2 d in distilled water to induce fungal sporulation. The release of aquatic
      hyphomycete spores increased when the water was supplemented with low
      concentrations of Ca(2+) (5 ug/L), Zn(2+) (2.5 ug/L), Cu(2+) (0.5 ug/L), or
      Cd(2+) (0.125 ug/L). Higher supplement concentrations inhibited sporulation. Over
      the concentration range used, the sporulation response was generally best
      described by a quadratic regression, suggesting a biphasic or hormetic response.
      A similar pattern was found with the number of fungal species as the dependent
      variable. Anguillospora filiformis and Anguillospora longissima were generally
      least inhibited by metal supplements, and Ca(2+) was the least and Cd(2+) the
      most toxic metal. Combinations of metals had a more severe effect on fungal
      sporulation than predicted from addition of the effects of the metals in
      isolation. The biological significance of the hormetic response is unclear;
      however, acknowledging it is clearly relevant for establishing guidelines or
      recommendations in toxicology.

PMID- 21953528
TI  - Transdermal delivery using a novel electrochemical device, part 1: device design
      and in vitro release/permeation of fentanyl.
AB  - A new type of electrochemical transdermal patch has been investigated using
      release/permeation experiments with excised nude mouse skin. The patch comprises
      a drug-containing hydrogel sandwiched between two electrodes that are arranged
      parallel to the skin surface. The objective was to determine the mechanism of
      working of enhanced flux for the drug fentanyl when low voltages are applied. The
      results indicate that a voltage-induced hydrolysis of the water present in the
      patch's hydrogel occurs. This causes a pH shift that results in deprotonization
      of the fentanyl and hence enhanced release/permeation. The enhanced flux is up to
      approximately 30 MUg/(cm(2) h) over 20 h and requires only a low-voltage
      application over a duration of just 60 s. Because the enhancement mechanism
      occurs in the patch and not in the skin, the potential for substantially reduced
      skin irritation compared with iontophoresis is given.

PMID- 21953529
TI  - Synthesis and cytotoxicity studies of novel 2-Hydrazonylpyrido[2,3-b]pyrazin
      3(4H)-ones.
AB  - In an attempt to develop potent antitumor agents, a series of novel 2
      hydrazonylpyrido[2,3-b]pyrazin-3(4H)-one derivatives were designed and
      synthesized. All the prepared compounds were screened for their cytotoxic
      activities against A549, MDA-MB-231 and HT-29 cell lines in vitro.
      Pharmacological data indicated that five of the target compounds showed
      cytotoxicity against A549 cell line below a concentration of 1 uM. Compound 15g
      was the most potent one with IC(50)  values of 0.19, 2.11 and 2.15 uM against
      A549, MDA-MB-231 and HT29 cell lines, respectively.

PMID- 21953530
TI  - Giant cell aortitis of the ascending aorta without signs or symptoms of systemic
      vasculitis is associated with elevated risk of distal aortic events.

PMID- 21953531
TI  - Olfaction in pathologically proven patients with multiple system atrophy.

PMID- 21953532
TI  - Cytotoxicity and glycan-binding profile of a D-galactose-binding lectin from the
      eggs of a Japanese sea hare (Aplysia kurodai).
AB  - A divalent cation-independent 16 kDa D-galactose binding lectin (AKL-2) was
      isolated from eggs of sea hare, Aplysia kurodai. The lectin recognized D
      galactose and D-galacturonic acid and had a 32 kDa dimer consisting of two
      disulfide-bonded 16 kDa subunits. Eighteen N-terminus amino acids were identified
      by Edman degradation, having unique primary structure. Lectin blotting analysis
      with horseradish peroxidase-conjugated lectins has shown that AKL-2 was a
      glycoprotein with complex type oligosaccharides with N-acetyl D-glucosamine and
      mannose at non-reducing terminal. Two protein bands with 38 and 36 kDa in the
      crude extract of sea hare eggs after purification of the lectin was isolated by
      AKL-2-conjugated Sepharose column and elution with 0.1 M lactose containing
      buffer. It suggested that the lectin binds with an endogenous ligand in the eggs.
      AKL-2 kept extreme stability on haemagglutination activity if it was treated at
      pH 3 and 70  degrees C for 1 h. Glycan binding profile of AKL-2 by frontal
      affinity chromatography technology using 15 pyridylamine labeled oligosaccharides
      has been appeared that the lectin uniquely recognized globotriose (Galalpha1
      4Galbeta1-4Glc; Gb3) in addition to bi-antennary complex type N-linked
      oligosaccharides with N-acetyllactosamine. Surface plasmon resonance analysis of
      AKL-2 against a neo-glycoprotein, Gb3-human serum albumin showed the k(ass) and
      k(diss) values are 2.4 * 103 M-1 s-1 and 3.8 * 10-3 s-1, respectively. AKL-2
      appeared cytotoxicity against both Burkitt's lymphoma Raji cell and
      erythroleukemia K562. The activity to Raji by the lectin was preferably cancelled
      by the co-presence of melibiose mimicing Gb3. On the other hand, K562 was
      cancelled effectively by lactose than melibiose. It elucidated that AKL-2 had
      cytotoxic ability mediated glycans structure to cultured cells.

PMID- 21953533
TI  - Evidence-based laboratory medicine: how well do laboratories follow
      recommendations and guidelines? The Cardiac Marker Guideline Uptake in Europe
      (CARMAGUE) study.

PMID- 21953534
TI  - Overexpression of HOXB7 and homeobox genes characterizes multiple myeloma
      patients lacking the major primary immunoglobulin heavy chain locus
      translocations.
AB  - Homeobox (HOX) gene transcription factors are frequently deregulated in
      hematologic malignancies and involved in leukemogenic transformation [1].
      Moreover, their overexpression has been associated with tumoral-induced
      neoangiogenesis in solid cancer [2]. The expression and the role of these genes
      have not yet been completely elucidated in multiple myeloma (MM). Recently, we
      reported that a small fraction of MM patients shows a HOXB7 overexpression as
      compared with normal samples and that HOXB7 expression correlates with bone
      marrow angiogenesis and the production of the proangiogenic factors by MM cells
      [3]. Other authors previously reported that HOXA cluster genes are expressed in a
      small fraction of MM patients [4]. Herein, we extended our previous evidences
      with the evaluation of the expression level of HOXB7 and the other gene family
      members in a large number of primary MM cells in relationship with the different
      molecular subgroups of MM and the presence of specific chromosome translocations.
      We found that HOXB7 and other genes of HOX family have a preferential
      distribution based on the characteristics of molecular MM subtypes based on the
      translocations/cyclins (TC) classification, suggesting a potential relationship
      between HOX genes expression, angiogenesis, and molecular features of MM
      patients.

PMID- 21953535
TI  - Response of soil organic carbon mineralization in typical Karst soils following
      the addition of 14C-labeled rice straw and CaCO3.
AB  - BACKGROUND: Organic substrates and calcium are important factors controlling
      organic matter turnover in Karst soils. To understand their effects on soil
      organic carbon (SOC) mineralization, an incubation experiment was conducted
      involving a control treatment (CK), the addition of a (14)C-labeled rice straw
      (T1), CaCO(3) (T2), and both (14)C-labeled rice straw and CaCO(3) (T3) to two
      types of Karst soils (terra fusca and rendzina) and a red soil from southwestern
      China. RESULTS: Cumulative mineralization of the rice straw over 100 days in
      rendzina (22.96 mg kg(-1)) and terra fusca (23.19 mg kg(-1)) was higher than in
      the red soil (15.48 mg kg(-1); P < 0.05). Cumulative mineralization of native SOC
      decreased following addition of (14)C-labeled rice straw in the rendzina and
      terra fusca but increased in the red soil (negative and positive priming effects
      on native SOC). The turnover times of (14)C-labeled microbial biomass C (MBC) in
      the red soil, terra fusca and rendzina were 71 +/- 2, 243 +/- 20 and 254 +/- 45
      days, respectively. By adding CaCO(3), the accumulation of SOC was greater in the
      Karst soils than in the red soil. CONCLUSION: Although the interactions between
      rice straw decomposition and priming effects on native SOC are not yet
      understood, there was considerable variation between Karst and red soils. Soil
      calcium was a positive factor in maintaining SOC stability. MBC from rice straws
      was stable in terra fusca and rendzina, whereas it was active in the red soil.
      The Karst soils (terra fusca and rendzina) used in this study benefited SOC
      accumulation.

PMID- 21953536
TI  - Stabilization of proteins by nanoencapsulation in sugar-glass for tissue
      engineering and drug delivery applications.

PMID- 21953538
TI  - Surgical education in the United States 2010: developing intellectual, technical
      and human values.

PMID- 21953537
TI  - Longitudinal stability and developmental properties of salivary cortisol levels
      and circadian rhythms from childhood to adolescence.
AB  - This study aimed to (1) identify a stable, trait-like component to cortisol and
      its circadian rhythm, and (2) investigate individual differences in developmental
      trajectories of HPA-axis maturation. Multiple salivary cortisol samples were
      collected longitudinally across four assessments from age 9 (3rd grade) through
      age 15 (9th grade) in a community sample of children (N = 357). Sophisticated
      statistical models examined cortisol levels and its rhythm over time; effects of
      age, puberty and gender were primarily considered. In addition to situation
      specific and stable short-term or epoch-specific cortisol components, there is a
      stable, trait-like component of cortisol levels and circadian rhythm across
      multiple years covering the transition from childhood into adolescence. Youth had
      higher cortisol and flatter circadian rhythms as they got older and more
      physically developed. Girls had higher cortisol, stronger circadian rhythms, and
      greater developmental influences across adolescence. Distinguishing a stable,
      trait-like component of cortisol level and its circadian rhythm provides the
      empirical foundation for investigating putative mechanisms underlying individual
      differences in HPA functioning. The findings also provide important descriptive
      information about maturational processes influencing HPA-axis development.

PMID- 21953539
TI  - Synergistic antidyskinetic effects of topiramate and amantadine in animal models
      of Parkinson's disease.
AB  - L-Dopa-induced dyskinesia in patients with Parkinson's disease can be alleviated
      by amantadine, an antagonist at N-methyl-D-aspartate glutamate receptors. The
      antiepileptic drug topiramate, which blocks alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid receptors, has also been shown to reduce dyskinesia. The
      purpose of this study was to examine the behavioral pharmacology of topiramate
      alone and in combination with amantadine in animal models of PD and L-dopa
      induced dyskinesia. The effects of topiramate (5-20 mg/kg) and amantadine (5-20
      mg/kg) on abnormal involuntary movements (the rat homologue of dyskinesia) and
      Rotarod performance were assessed alone and in combination in the 6
      hydroxydopamine-lesioned rat following chronic L-dopa treatment. Dyskinesia,
      parkinsonian disability, and "on-time" were assessed in the MPTP-lesioned
      nonhuman primate following administration of topiramate (5-20 mg/kg) and
      amantadine (0.1-1.0 mg/kg) alone and in combination. Topiramate and amantadine
      dose-dependently reduced dyskinesia in the 6-hydroxydopamine-lesioned rat,
      whereas topiramate reduced Rotarod performance; there was no effect on
      parkinsonian disability in the MPTP-lesioned nonhuman primate, in which both
      drugs reduced dyskinesia. Topiramate and amantadine exhibited differential
      antidyskinetic effects on dyskinesia elicited by the dopamine D1 receptor agonist
      SKF 38393 (2 mg/kg). Subthreshold doses of both drugs in combination had a
      synergistic effect on dyskinesia in the 6-hydroxydopamine-lesioned rat, with no
      worsening of motor performance; this effect was confirmed in the MPTP-lesioned
      nonhuman primate, with a selective reduction in "bad on-time." These data confirm
      the antidyskinetic potential of topiramate and suggest that combination with low
      dose amantadine may allow better reduction of dyskinesia with no adverse motor
      effects.

PMID- 21953540
TI  - Integrated model for denosumab and ibandronate pharmacodynamics in postmenopausal
      women.
AB  - This study aims to characterize the pharmacodynamic properties of denosumab, a
      RANK ligand inhibitor, and ibandronate, a bisphosphonate, using an integrated
      bone homeostasis model in postmenopausal women. Mean temporal profiles of
      denosumab, serum and urine N-telopeptide (sNTX, uNTX), lumbar spine bone mineral
      density (BMD) following denosumab administration, and urine C-telopeptide (uCTX)
      and lumbar spine BMD upon ibandronate administration were extracted from the
      literature. A mechanistic model was developed that integrates denosumab
      pharmacokinetics with binding to RANK ligand and ibandronate inhibition of
      osteoclast precursor differentiation to active osteoclasts (AOC). Biomarker
      concentrations were linked to the AOC pool. The BMD was characterized by a
      turnover model with stimulation of bone formation and degradation by AOB (active
      osteoblasts) and AOC pools. The estimated basal sNTX, uNTX and uCTX
      concentrations were 7.24 nm, 14.4 nmol/mmolCr and 31ug/mmolCr. The BMD
      degradation rate was 0.00161 day(-1) with stimulation constants associated with
      AOB and AOC of 1214 and 790 pm(-1) . The plasma ibandronate concentration
      producing 50% of maximum inhibition of osteoclast differentiation was 522 ng/l.
      The integrated model, which incorporates multiple pathways of therapeutic
      intervention, quantitatively describes changes in clinical biomarkers of bone
      turnover and BMD after denosumab and ibandronate exposures in postmenopausal
      women.

PMID- 21953542
TI  - Evaluating f-element bonding from structure and thermodynamics.
AB  - The practical goal to measure and understand the thermodynamic properties of
      molecules and materials containing f-elements is often achieved through indirect
      methods. Of the characterization tools available to inorganic chemists, few are
      more powerful than X-ray crystallography. Yet for lanthanides and actinides,
      interpretation of a bond length is a challenging undertaking that involves a
      complex interplay of steric and electronic forces. In this Concept article, we
      perform an analysis of selected examples in which structural criteria alone have
      been used to draw qualitative conclusions about chemical bonding. In other
      instances for which such an analysis is not valid, thermodynamic information is
      evaluated side by side with structural data to provide reasonable interpretations
      of a covalent/ionic mode of bonding. A geometric variation larger than 3sigma is
      not necessarily correlated to a change in bonding, nor is an increase in bond
      energy related to a bond with more covalent character. However, careful
      consideration of thermodynamic information can lead to reasonable interpretations
      of electronic structure, and may provide a more reliable benchmark for the
      theoretical methods which can describe f-elements.

PMID- 21953541
TI  - Predicting the survival of experimental ischaemic small bowel using
      intraoperative near-infrared fluorescence angiography.
AB  - BACKGROUND: Predicting the long-term viability of ischaemic bowel during surgery
      is challenging. The aim was to determine whether intraoperative near-infrared
      angiography (NIR-AG) of ischaemic bowel might provide metrics that were
      predictive of long-term outcome. METHODS: NIR-AG using indocyanine green was
      performed on 24 pigs before, and after inducing bowel ischaemia to determine the
      feasibility of NIR-AG for detecting compromised perfusion. Contrast-to-background
      ratio (CBR) over time was measured in regions of interest throughout the bowel,
      and various metrics of the CBR-time curve were developed. Sixty rat small bowels,
      with or without strangulation, were imaged during surgery and on day 3 after
      operation. CBR metrics and clinical findings were assessed quantitatively for
      their ability to predict animal survival, histological grade of ischaemic injury
      and visible necrosis on day 3. RESULTS: In ischaemic pig small bowel, various
      qualitative and quantitative CBR metrics appeared to correlate with bowel injury
      as a function of distance from normal bowel. In rats, intraoperative clinical
      assessment showed high specificity but low sensitivity for predicting outcome on
      day 3 after operation. Qualitative patterns of the CBR-time curve, such as
      absence of an arterial inflow peak and presence of a NIR filling defect, resulted
      in better prediction of survival (90 per cent), histological grade (85 per cent)
      and visible necrosis on day 3 (92 per cent). CONCLUSION: Survival of ischaemic
      bowel was predicted by intraoperative NIR-AG with greater accuracy than clinical
      evaluation alone.

PMID- 21953544
TI  - Acanthamoeba polyphaga, a potential environmental vector for the transmission of
      food-borne and opportunistic pathogens.
AB  - The endosymbiotic relationship could represent for many bacteria an important
      condition favouring their spread in the environment and in foods. For this
      purpose we studied the behaviour of some food-borne and opportunistic pathogens
      (Listeria monocytogenes, Staphylococcus aureus, Enterococcus faecalis, Salmonella
      enterica serovar Enteritidis, Aeromonas hydrophila, Yersinia enterocolitica) when
      internalized in Acanthamoeba polyphaga. Our results confirm the capability of the
      bacteria tested to grow within amoebal hosts. We can observe two types of
      interactions of the bacteria internalized in A. polyphaga. The first type, showed
      by Y. enterocolitica and A. hydrophila, was characterized by an early
      replication, probably followed by the killing and digestion of the bacteria. The
      second type, showed by E. faecalis and S. aureus was characterized by the
      persistence and grow inside the host without lysis. Lastly, when amoebae were co
      cultured with L. monocytogenes and S. Enteritidis, an eclipse phase followed by
      an active intracellular growth was observed, suggesting a third type of predator
      prey trend. The extracellular count in presence of A. polyphaga, as a result of
      an intracellular multiplication and subsequent release, was characterized by an
      increase of E. faecalis, S. aureus, L. monocytogenes and S. Enteritidis, and by a
      low or absent cell count for Y. enterocolitica and A. hydrophila. Our study
      suggests that the investigated food-borne and opportunistic pathogens are, in
      most cases, able to interact with A. polyphaga, to intracellularly replicate and,
      lastly, to be potentially spread in the environment, underlining the possible
      role of this protozoan in food contamination.

PMID- 21953543
TI  - Slow phasic and tonic activity of ventral pallidal neurons during cocaine self
      administration.
AB  - Ventral pallidal (VP) neurons exhibit rapid phasic firing patterns within seconds
      of cocaine-reinforced responses. The present investigation examined whether VP
      neurons exhibited firing rate changes: (1) over minutes during the inter-infusion
      interval (slow phasic patterns) and/or (2) over the course of the several-hour
      self-administration session (tonic firing patterns) relative to pre-session
      firing. Approximately three-quarters (43/54) of VP neurons exhibited slow phasic
      firing patterns. The most common pattern was a post-infusion decrease in firing
      followed by a progressive reversal of firing over minutes (51.16%; 22/43). Early
      reversals were predominantly observed anteriorly whereas progressive and late
      reversals were observed more posteriorly. Approximately half (51.85%; 28/54) of
      the neurons exhibited tonic firing patterns consisting of at least a two-fold
      change in firing. Most cells decreased firing during drug loading, remained low
      over self-administration maintenance, and reversed following lever removal. Over
      a whole experiment (tonic) timescale, the majority of neurons exhibited an
      inverse relationship between calculated drug level and firing rates during
      loading and post-self-administration behaviors. Fewer neurons exhibited an
      inverse relationship of calculated drug level and tonic firing rate during self
      administration maintenance but, among those that did, nearly all were progressive
      reversal neurons. The present results show that, similar to its main afferent the
      nucleus accumbens, VP exhibits both slow phasic and tonic firing patterns during
      cocaine self-administration. Given that VP neurons are principally GABAergic, the
      predominant slow phasic decrease and tonic decrease firing patterns within the VP
      may indicate a disinhibitory influence upon its thalamocortical, mesolimbic, and
      nigrostriatal targets during cocaine self-administration.

PMID- 21953545
TI  - The correspondence between proximal phalanx morphology and locomotion:
      implications for inferring the locomotor behavior of fossil catarrhines.
AB  - Phalanges are considered to be highly informative in the reconstruction of
      extinct primate locomotor behavior since these skeletal elements directly
      interact with the substrate during locomotion. Variation in shaft curvature and
      relative phalangeal length has been linked to differences in the degree of
      suspension and overall arboreal locomotor activities. Building on previous work,
      this study investigated these two skeletal characters in a comparative context to
      analyze function, while taking evolutionary relationships into account. This
      study examined the correspondence between proportions of suspension and overall
      substrate usage observed in 17 extant taxa and included angle of curvature and
      relative phalangeal length. Predictive models based on these traits are reported.
      Published proportions of different locomotor behaviors were regressed against
      each phalangeal measurement and a size proxy. The relationship between each
      behavior and skeletal trait was investigated using ordinary least-squares,
      phylogenetic generalized least-squares (pGLS), and two pGLS transformation
      methods to determine the model of best-fit. Phalangeal curvature and relative
      length had significant positive relationships with both suspension and overall
      arboreal locomotion. Cross-validation analyses demonstrated that relative length
      and curvature provide accurate predictions of relative suspensory behavior and
      substrate usage in a range of extant species when used together in predictive
      models. These regression equations provide a refined method to assess the amount
      of suspensory and overall arboreal locomotion characterizing species in the
      catarrhine fossil record.

PMID- 21953547
TI  - Regional and subcellular distribution of the receptor-targeting protein PIST in
      the rat central nervous system.
AB  - Protein interacting specifically with Tc10, PIST, is a Golgi-associated sorting
      protein involved in regulating cell-surface targeting of plasma membrane
      receptors. The present study provides the first comprehensive description of PIST
      distribution in the mammalian central nervous system and of its subcellular
      localization by immunocytochemistry. PIST is distributed widely throughout the
      neuraxis, predominantly associated with neuronal cell bodies and dendrites. In
      hippocampal neurons, in vitro and in situ, PIST displayed a patchy subcellular
      distribution in an area surrounding the nucleus and extending into one of the
      major dendrites. By colocalization with the trans-Golgi marker TGN38, we were
      able to show that PIST is associated largely but not exclusively with the trans
      Golgi network in central neurons. High or moderate to high levels of PIST-like
      immunoreactivity were found in cortical areas, in particular in layer V of the
      neocortex. The motor cortex was most strongly labeled. Also, the piriform and
      insular cortices displayed strong PIST labeling. In the hippocampus, CA2 but not
      CA1 or CA3 pyramidal cells displayed strong PIST-labeling, extending into their
      apical dendrites. In the thalamus, ventrolateral and laterodorsal nuclei were
      most strongly stained, whereas in the hypothalamus the supraoptic nucleus stood
      out with strong immunoreactivity. Strikingly, in the brainstem all cranial nerve
      motor nuclei were PIST-positive at varying levels, which is in keeping with the
      prominent expression of PIST in forebrain motor areas. This selective
      distribution of PIST suggests that the protein serves distinctive roles in
      specific neuronal populations, establishing functionally distinct zones, for
      instance, in the hippocampus.

PMID- 21953546
TI  - Noninvasive imaging identifies new roles for cyclooxygenase-2 in choline and
      lipid metabolism of human breast cancer cells.
AB  - The expression of cyclooxygenase-2 (COX-2) is observed in approximately 40% of
      breast cancers. A major product of the COX-2-catalyzed reaction, prostaglandin
      E(2), is an inflammatory mediator that participates in several biological
      processes, and influences invasion, vascularization and metastasis. Using
      noninvasive MRI and MRS, we determined the effect of COX-2 downregulation on the
      metabolism and invasion of intact poorly differentiated MDA-MB-231 human breast
      cancer cells stably expressing COX-2 short hairpin RNA. Dynamic tracking of
      invasion, extracellular matrix degradation and metabolism was performed with an
      MRI- and MRS-compatible cell perfusion assay under controlled conditions of pH,
      temperature and oxygenation over the course of 48  h. COX-2-silenced cells
      exhibited a significant decrease in invasion relative to parental cells that was
      consistent with the reduced expression of invasion-associated matrix
      metalloproteinase genes and an increased level of the tissue inhibitor of
      metalloproteinase-1. We identified, for the first time, a role for COX-2 in
      mediating changes in choline phospholipid metabolism, and established that
      choline kinase expression is partly dependent on COX-2 function. COX-2 silencing
      resulted in a significant decrease in phosphocholine and total choline that was
      detected by MRS. In addition, a significant increase in lipids, as well as lipid
      droplet formation, was observed. COX-2 silencing transformed parental cell
      metabolite patterns to those characteristic of less aggressive cancer cells.
      These new functional roles of COX-2 may identify new biomarkers and new targets
      for use in combination with COX-2 targeting to prevent invasion and metastasis.

PMID- 21953548
TI  - The autoantigen DNA topoisomerase I interacts with chemokine receptor 7 and
      exerts cytokine-like effects on dermal fibroblasts.
AB  - OBJECTIVE: Previous studies have demonstrated that, once released into the
      extracellular environment, the systemic sclerosis (SSc)-associated autoantigen
      DNA topoisomerase I (topo I) binds specifically to the surface of fibroblasts via
      an unknown receptor. We extended these results by identifying topo I-mediated
      cellular effects and characterizing the specific target of topo I on fibroblast
      surfaces. METHODS: Purified topo I was used to investigate intracellular
      signaling pathway activation and tested for cell migration. To demonstrate the
      expression of specific chemokine receptors on fibroblasts, we performed
      immunoblotting and flow cytometry. To evaluate the direct interaction between
      chemokine receptor and topo I, a protein-protein based enzyme-linked
      immunosorbent assay (ELISA) was used. Finally, topo I coupled to the fluorochrome
      phycoerythrin (PE) was used to investigate competition of topo I specific binding
      on fibroblast surfaces with chemokine ligand. RESULTS: Topo I stimulated the
      phosphorylation of phospholipase Cgamma1, c-Raf, ERK-1/2, and p38 MAPK,
      intracellular signaling pathways that stimulated fibroblast migration via a
      G(alphai)  protein-coupled receptor. CCR7 was found to interact directly with
      topo I. Furthermore, its ligand, CCL21, competed in vitro for this interaction
      and in vivo with the binding of PE-coupled topo I to fibroblast surfaces.
      CONCLUSION: These new roles of topo I in fibroblast physiology and the
      identification of its target on the cell surface demonstrate that topo I is a
      bifunctional autoantigen and open up new perspectives of study in the field of
      SSc-associated anti-topo I autoantibodies.

PMID- 21953549
TI  - Ecosystem functions and densities of contributing functional groups respond in a
      different way to chemical stress.
AB  - Understanding whether and to what extent ecosystem functions respond to chemicals
      is a major challenge in environmental toxicology. The available data gathered by
      ecosystem-level experiments (micro- and mesocosms) often describe the responses
      of taxa densities to stress. However, whether these responses are proportional to
      the responses of associated ecosystem functions to stress is unclear. By
      combining a carbon budget modeling technique with data from a standardized
      microcosm experiment with a known community composition, we quantified three
      ecosystem functions (net primary production [NPP], net mesozooplankton production
      [NZP], and net bacterial production [NBP]) at three Cu concentrations, with a
      control. Changes of these ecosystem functions with increasing chemical
      concentrations were not always proportional to the Cu effects on the densities of
      the contributing functional groups. For example, Cu treatments decreased
      mesozooplankton density by 100-fold and increased phytoplankton density 10- to
      100-fold while increasing NZP and leaving NPP unaltered. However, in contrast, Cu
      affected microzooplankton and the associated function (NBP) in a comparable way.
      We illustrate that differences in the response of phytoplankton/mesozooplankton
      densities and the associated ecosystem functions to stress occur because
      functional rates (e.g., photosynthesis rates/ingestion rates) vary among Cu
      treatments and in time. These variations could be explained by food web ecology
      but not by direct Cu effects, indicating that ecology may be a useful basis for
      understanding environmental effects of stressors.

PMID- 21953550
TI  - Novel pH-sensitive physical hydrogels of carboxymethyl scleroglucan.
AB  - A carboxymethyl derivative of scleroglucan (Scl-CM) with derivatization degree
      300 +/- 10 was synthesized and characterized by Fourier transform infrared
      spectroscopy, potentiometer titration, mucus adhesion studies, and rheological
      measurements. Rheological measurements showed the ability of the polymer to
      undergo sol-gel transitions even in the absence of salts. Swelling experiments,
      performed on freeze-dried samples in different media, showed good affinity of
      these hydrogels toward the aqueous media and a pH-sensitive behavior. Four
      nonsteroidal anti-inflammatory drugs (NSAIDs) were loaded into the physical
      hydrogels obtained from 2.0% (w/v) solutions of the polymer. The results of the
      release studies carried out in conditions simulating the gastrointestinal tract
      showed that the new hydrogels could be suggested for the modified oral delivery
      of NSAIDs, particularly damaging for the gastric mucosa. In vivo studies proved
      the biocompatibility of the matrix and the absence of any gastric damage for
      administration of ulcerogenic doses of diclofenac loaded into the hydrogel
      (DIC/Scl-CM-300). Moreover, DIC/Scl-CM-300 was found to be effective in
      peripheral analgesia.

PMID- 21953551
TI  - The impact of solubility and electrostatics on fibril formation by the H3 and H4
      histones.
AB  - The goal of this study was to examine fibril formation by the heterodimeric
      eukaryotic histones (H2A-H2B and H3-H4) and homodimeric archaeal histones (hMfB
      and hPyA1). The histone fold dimerization motif is an obligatorily domain-swapped
      structure comprised of two fused helix:beta-loop:helix motifs. Domain swapping
      has been proposed as a mechanism for the evolution of protein oligomers as well
      as a means to form precursors in the formation of amyloid-like fibrils. Despite
      sharing a common fold, the eukaryotic histones of the core nucleosome and
      archaeal histones fold by kinetic mechanisms of differing complexity with
      transient population of partially folded monomeric and/or dimeric species. No
      relationship was apparent between fibrillation propensity and equilibrium
      stability or population of kinetic intermediates. Only H3 and H4, as isolated
      monomers and as a heterodimer, readily formed fibrils at room temperature, and
      this propensity correlates with the significantly lower solubility of these
      polypeptides. The fibrils were characterized by ThT fluorescence, FTIR, and far
      UV CD spectroscopies and electron microscopy. The helical histone fold comprises
      the protease-resistant core of the fibrils, with little or no protease protection
      of the poorly structured N-terminal tails. The highly charged tails inhibit
      fibrillation through electrostatic repulsion. Kinetic studies indicate that H3
      and H4 form a co-fibril, with simultaneous incorporation of both histones. The
      potential impact of H3 and H4 fibrillation on the cytotoxicity of extracellular
      histones and alpha-synuclein-mediated neurotoxicity and fibrillation is
      considered.

PMID- 21953553
TI  - The coupling constant polarizability and hyperpolarizabilty of 1J(NH) in N
      methylacetamide, and its application for the multipole spin-spin coupling
      constant polarizability/reaction field approach to solvation.
AB  - We present a benchmark study of a combined multipole spin-spin coupling constant
      (SSCC) polarizability/reaction field (MJP/RF) approach to the calculation of both
      specific and bulk solvation effects on SSCCs of solvated molecules. The MJP/RF
      scheme is defined by an expansion of the SSCCs of the solvated molecule in terms
      of coupling constant dipole and quadrupole polarizabilities and
      hyperpolarizabilities derived from single molecule ab initio calculations. The
      solvent electric field and electric field gradient are calculated based on data
      derived from molecular dynamics (MD) simulations thereby accounting for solute
      solvent dynamical effects. The MJP/RF method is benchmarked against polarizable
      QM/MM calculations for the one-bond N-H coupling constant in N-methylacetamide.
      The best agreement between the MJP/RF and QM/MM approaches is found by truncating
      the electric field expansion in the MJP/RF approach at the linear electric field
      level. In addition, we investigate the sensitivity of the results due to the
      choice of one-electron basis set in the ab initio calculations of the coupling
      constant (hyper-)polarizabilities and find that they are affected by the basis
      set in a way similar to the coupling constants themselves.

PMID- 21953552
TI  - Translationally controlled tumor protein induces mitotic defects and chromosome
      missegregation in hepatocellular carcinoma development.
AB  - Emerging evidence implicates the chromodomain helicase/ATPase DNA binding protein
      1-like gene (CHD1L) as a specific oncogene in human hepatocellular carcinoma
      (HCC). To better understand the molecular mechanisms underlying HCC cases
      carrying CHD1L amplification (>50% HCCs), we identified a CHD1L target,
      translationally controlled tumor protein (TCTP), and investigated its role in HCC
      progression. Here, we report that CHD1L protein directly binds to the promoter
      region (nt -733 to -1,027) of TCTP and activates TCTP transcription.
      Overexpression of TCTP was detected in 40.7% of human HCC samples analyzed and
      positively correlated with CHD1L overexpression. Clinically, overexpression of
      TCTP was significantly associated with the advanced tumor stage (P = 0.037) and
      overall survival time of HCC patients (P = 0.034). In multivariate analyses, TCTP
      was determined to be an independent marker associated with poor prognostic
      outcomes. In vitro and in vivo functional studies in mice showed that TCTP has
      tumorigenic abilities, and overexpression of TCTP induced by CHD1L contributed to
      the mitotic defects of tumor cells. Further mechanistic studies demonstrated that
      TCTP promoted the ubiquitin-proteasome degradation of Cdc25C during mitotic
      progression, which caused the failure in the dephosphorylation of Cdk1 on Tyr15
      and decreased Cdk1 activity. As a consequence, the sudden drop of Cdk1 activity
      in mitosis induced a faster mitotic exit and chromosome missegregation, which led
      to chromosomal instability. The depletion experiment proved that the
      tumorigenicity of TCTP was linked to its role in mitotic defects. CONCLUSION:
      Collectively, we reveal a novel molecular pathway (CHD1L/TCTP/Cdc25C/Cdk1), which
      causes the malignant transformation of hepatocytes with the phenotypes of
      accelerated mitotic progression and the production of aneuploidy.

PMID- 21953554
TI  - Fast and accurate computation schemes for evaluating vibrational entropy of
      proteins.
AB  - Standard normal mode analysis (NMA) method is able to calculate vibrational
      entropy of proteins, but it is computationally intensive, especially for large
      proteins. To evaluate vibrational entropy efficiently and accurately, we, here,
      propose computation schemes based on coarse-grained NMA methods. This can be
      achieved by rescaling coarse-grained results with a specific factor that is
      derived on the basis of the linear correlation of protein vibrational entropy
      between standard NMA and coarse-grained NMA. Our coarse-grained NMA computation
      schemes can repeat correctly and efficiently the results of standard NMA for
      large proteins.

PMID- 21953555
TI  - In silico evaluation of proposed biosynthetic pathways for the unique dithiolate
      ligand of the H-cluster of [FeFe]-hydrogenase.
AB  - The biosynthesis of the active site of the [FeFe]-hydrogenases (H-cluster)
      remains a tantalizing puzzle due to its unprecedented and complex ligand
      environment. It contains a [2Fe] cluster ([2Fe](H)) bearing cyanide and carbon
      monoxide ligands attached to low-valence Fe ions and an abiological dithiolate
      ligand (SCH(2)XCH(2)S)(2-) that bridges the two iron centers. Various
      experimentally testable hypotheses have already been put forward regarding the
      precursor molecule and the biosynthetic mechanism that leads to the formation of
      the dithiolate ligand. In this work, we report a density functional theory-based
      theoretical evaluation of these hypotheses. We find preference for a
      mechanistically simple and energetically favorable pathway that includes known
      radical-SAM (S-adenosylmethionine) catalyzed reactions. We modeled this pathway
      using a long alkyl chain precursor molecule that leads to the formation of
      pronanadithiolate (X = CH(2)). However, the same pathway can be readily adopted
      for the biosynthesis of the dithiomethylamine (X = NH) or the dithiomethylether
      (X = O) analog, provided that the proper precursor molecule is available.

PMID- 21953556
TI  - New insights in quantum chemical topology studies using numerical grid-based
      analyses.
AB  - New insights in Quantum Chemical Topology of one-electron density functions have
      been proposed here by using a recent grid-based algorithm (Tang et al., J Phys
      Condens Matter 2009, 21, 084204), initially designed for the decomposition of the
      electron density. Beyond the charge analysis, we show that this algorithm is
      suitable for different scalar functions showing a more complex topology, that is,
      the Laplacian of the electron density, the electron localization function (ELF),
      and the molecular electrostatic potential (MEP). This algorithm makes use of a
      robust methodology enabling to numerically assign the data points of three
      dimensional grids to basin volumes, and it has the advantage of requiring only
      the values of the scalar function without details on the wave function used to
      build the grid. Our implementation is briefly outlined (program named TopChem),
      its capabilities are examined, and technical aspects in terms of CPU requirement
      and accuracy of the results are discussed. Illustrative examples for individual
      molecules and crystalline solids obtained with gaussian and plane-wave-based
      density functional theory calculations are presented. Special attention was given
      to the MEP because its topological analysis is complex and scarce.

PMID- 21953557
TI  - Using Huffman coding method to visualize and analyze DNA sequences.
AB  - On the basis of the Huffman coding method, we propose a new graphical
      representation of DNA sequence. The representation can avoid degeneracy and loss
      of information in the transfer of data from a DNA sequence to its graphical
      representation. Then a multicomponent vector from the representation is
      introduced to characterize quantitatively DNA sequences. The components of the
      vector are derived from the graphical representation of DNA primary sequence. The
      examination of similarities and dissimilarities among the complete coding
      sequences of beta-globin gene of 11 species and six ND6 proteins shows the
      utility of the scheme.

PMID- 21953558
TI  - Soft-core potentials in thermodynamic integration: comparing one- and two-step
      transformations.
AB  - Molecular dynamics-based free energy calculations allow the determination of a
      variety of thermodynamic quantities from computer simulations of small molecules.
      Thermodynamic integration (TI) calculations can suffer from instabilities during
      the creation or annihilation of particles. This "singularity" problem can be
      addressed with "soft-core" potential functions which keep pairwise interaction
      energies finite for all configurations and provide smooth free energy curves.
      "One-step" transformations, in which electrostatic and van der Waals forces are
      simultaneously modified, can be simpler and less expensive than "two-step"
      transformations in which these properties are changed in separate calculations.
      Here, we study solvation free energies for molecules of different hydrophobicity
      using both models. We provide recommended values for the two parameters alpha(LJ)
      and beta(C) controlling the behavior of the soft-core Lennard-Jones and Coulomb
      potentials and compare one- and two-step transformations with regard to their
      suitability for numerical integration. For many types of transformations, the one
      step procedure offers a convenient and accurate approach to free energy
      estimates.

PMID- 21953560
TI  - A semiempirical long-range corrected exchange correlation functional including a
      short-range Gaussian attenuation (LCgau-B97).
AB  - We applied an improved long-range correction scheme including a short-range
      Gaussian attenuation (LCgau) to the Becke97 (B97) exchange correlation
      functional. In the optimization of LCgau-B97 functional, the linear parameters
      are determined by least squares fitting. Optimizing MU parameter (0.2) that
      controls long-range portion of Hartree-Fock (HF) exchange to excitation energies
      of large molecules (Chai and Head-Gordon, J Chem Phys 2008, 128, 084106) and
      additional short-range Gaussian parameters (a = 0.15 and k = 0.9) that controls
      HF exchange inclusion ranging from short-range to mid-range (0.5-3 A) to ground
      state properties achieved high performances of LCgau-B97 simultaneously on both
      ground state and excited state properties, which is better than other tested
      semiempirical density functional theory (DFT) functionals, such as omegaB97,
      omegaB97X, BMK, and M0x-family. We also found that while a small MU value (~0.2)
      in LC-DFT is appropriate to the local excitation and intramolecular charge
      transfer excitation energies, a larger MU value (0.42) is desirable in the
      Rydberg excitation-energy calculations.

PMID- 21953559
TI  - Interactions between free radicals and a graphene fragment: physical versus
      chemical bonding, charge transfer, and deformation.
AB  - The adsorption of six free radicals (FRs) respectively on a graphene fragment was
      studied using a density functional tight-binding method with the inclusion of an
      empirical dispersion term in total energy. The results indicate that the
      different interaction paths between the FRs and the graphene lead to different
      forms of physical (PA) or chemical adsorptions (CA). The CA appears only in the
      condition where some of the nonhydrogen atoms are closer to the graphene, with
      the deformation occurring in the latter. The charge transfer increases with the
      increase in adsorption energy in every FR-graphene system. Although the
      deformation in the graphene is negligible in all PA cases, the FR is closer to
      the graphene and the graphene deformation is clearer in all CA cases, with all
      atomic displacements being larger than 0.1 A. Our findings are useful not only
      for FR scavenging but also for studying the interaction between general molecules
      and material surfaces.

PMID- 21953561
TI  - A theoretical study of CO adsorption on gold by Huckel theory and density
      functional theory calculations.
AB  - It is crucial to understand the nature of CO adsorption on gold so as to
      elucidate the mechanism of low-temperature CO oxidation on nanogold catalysts. We
      performed theoretical analysis of CO adsorption on gold by using Huckel theory
      and density functional theory (DFT) calculations. Huckel theory indicates that CO
      adsorption on gold is dominated by the electron distribution at the Au atom,
      which is greatly affected by neighboring Au atoms, coadsorbed or doping species.
      The increase of sigma-bonding electrons should weaken the CO adsorption, while
      the increase of pi-electrons should strengthen the adsorption. DFT calculations
      proved this prediction quantitatively for various systems, including CO
      adsorption on a Au(100)-hex surface with locally varying subsurface
      configurations and CO coadsorption with acceptor or donor species.

PMID- 21953562
TI  - Interplay between halogen bond and lithium bond in MCN-LiCN-XCCH (M = H, Li, and
      Na; X = Cl, Br, and I) complex: the enhancement of halogen bond by a lithium
      bond.
AB  - Quantum chemical calculations have been performed to study the complex of MCN
      LiCN-XCCH (M = H, Li, and Na; X = Cl, Br, and I). The aim is to study the
      cooperative effect between halogen bond and lithium bond. The alkali metal has an
      enhancing effect on the lithium bond, making it increased by 77 and 94% for the
      Li and Na, respectively. There is the cooperativity between the lithium bond and
      halogen bond. The former has a larger enhancing effect on the latter, being in a
      range of 11.7-29.4%. The effect of cooperativity on the halogen bond is dependent
      on the type of metal and halogen atoms. The enhancing mechanism has been analyzed
      in views with the orbital interaction, charge transfer, dipole moment,
      polarizability, atom charges, and electrostatic potentials. The results show that
      the electrostatic interaction plays an important role in the enhancement of
      halogen bond.

PMID- 21953563
TI  - An efficient parallel algorithm for the calculation of unrestricted canonical MP2
      energies.
AB  - We present details of our efficient implementation of full accuracy unrestricted
      open-shell second-order canonical Moller-Plesset (MP2) energies, both serial and
      parallel. The algorithm is based on our previous restricted closed-shell MP2 code
      using the Saebo-Almlof direct integral transformation. Depending on system
      details, UMP2 energies take from less than 1.5 to about 3.0 times as long as a
      closed-shell RMP2 energy on a similar system using the same algorithm. Several
      examples are given including timings for some large stable radicals with 90+
      atoms and over 3600 basis functions.

PMID- 21953564
TI  - Theoretical insights on the electron doping and Curie temperature in La-doped
      Sr2CrWO6.
AB  - The structure and electronic and magnetic properties of La(x)Sr(2-x)CrWO(6) (x =
      0.0, 0.5, 1.0, 1.5, 2.0) were investigated by using the density functional
      theory. With the increase of La doping, the extra electrons are injected into W
      5d orbitals, which makes the spin moments of W increase. In addition, the
      calculated Curie temperature and total magnetic moments decrease with the
      increase of the electron doping, in agreement with the experimental observation.
      This also means that the decrease of Curie temperature with the electron doping
      is intrinsic. Half metallic properties are obtained for x = 0.0, 0.5, 1.5, and
      2.0, whereas for x = 1.0, the compound is semiconducting.

PMID- 21953565
TI  - Molecular dynamics simulations of triflic acid and triflate ion/water mixtures: a
      proton conducting electrolytic component in fuel cells.
AB  - Triflic acid is a functional group of perflourosulfonated polymer electrolyte
      membranes where the sulfonate group is responsible for proton conduction.
      However, even at extremely low hydration, triflic acid exists as a triflate ion.
      In this work, we have developed a force-field for triflic acid and triflate ion
      by deriving force-field parameters using ab initio calculations and incorporated
      these parameters with the Optimized Potentials for Liquid Simulations - All Atom
      (OPLS-AA) force-field. We have employed classical molecular dynamics (MD)
      simulations with the developed force field to characterize structural and
      dynamical properties of triflic acid (270-450 K) and triflate ion/water mixtures
      (300 K). The radial distribution functions (RDFs) show the hydrophobic nature of
      CF(3) group and presence of strong hydrogen bonding in triflic acid and
      temperature has an insignificant effect. Results from our MD simulations show
      that the diffusion of triflic acid increases with temperature. The RDFs from
      triflate ion/water mixtures shows that increasing hydration causes water
      molecules to orient around the SO(3)(-) group of triflate ions, solvate the
      hydronium ions, and other water molecules. The diffusion of triflate ions,
      hydronium ion, and water molecules shows an increase with hydration. At lambda =
      1, the diffusion of triflate ion is 30 times lower than the diffusion of triflic
      acid due to the formation of stable triflate ion-hydronium ion complex. With
      increasing hydration, water molecules break the stability of triflate ion
      hydronium ion complex leading to enhanced diffusion. The RDFs and diffusion
      coefficients of triflate ions, hydronium ions and water molecules resemble
      qualitatively the previous findings using per-fluorosulfonated membranes.

PMID- 21953566
TI  - DynamO: a free O(N) general event-driven molecular dynamics simulator.
AB  - Molecular dynamics algorithms for systems of particles interacting through
      discrete or "hard" potentials are fundamentally different to the methods for
      continuous or "soft" potential systems. Although many software packages have been
      developed for continuous potential systems, software for discrete potential
      systems based on event-driven algorithms are relatively scarce and specialized.
      We present DynamO, a general event-driven simulation package, which displays the
      optimal O(N) asymptotic scaling of the computational cost with the number of
      particles N, rather than the O(N) scaling found in most standard algorithms.
      DynamO provides reference implementations of the best available event-driven
      algorithms. These techniques allow the rapid simulation of both complex and large
      (>10(6) particles) systems for long times. The performance of the program is
      benchmarked for elastic hard sphere systems, homogeneous cooling and sheared
      inelastic hard spheres, and equilibrium Lennard-Jones fluids. This software and
      its documentation are distributed under the GNU General Public license and can be
      freely downloaded from http://marcusbannerman.co.uk/dynamo.

PMID- 21953567
TI  - Design and synthesis of novel diphenyl oxalamide and diphenyl acetamide
      derivatives as anticonvulsants.
AB  - A series of novel N(1) -substituted-N(2) ,N(2) -diphenyl oxalamides 3a-l were
      synthesized in good yield by stirring diphenylcarbamoyl formyl chloride (2) and
      various substituted aliphatic, alicyclic, aromatic, heterocyclic amines in DMF
      and K(2) CO(3) . Also 2-substituted amino-N,N-diphenylacetamides 5a-m were
      designed by pharmacophore generation and synthesized by stirring 2-chloro-N,N
      diphenylacetamide (4) and various substituted amines in acetone using triethyl
      amine as a catalyst. All the synthesized compounds were screened for
      anticonvulsant activity in Swiss albino mice by MES and ScPTZ induced seizure
      tests. Neurotoxicity screening and behavioral testing was also carried out. Some
      of the synthesized test compounds were found to be more potent than the standard
      drug.

PMID- 21953569
TI  - X-chromosome-located microRNAs in immunity: might they explain male/female
      differences? The X chromosome-genomic context may affect X-located miRNAs and
      downstream signaling, thereby contributing to the enhanced immune response of
      females.
AB  - In this paper, we hypothesize that X chromosome-associated mechanisms, which
      affect X-linked genes and are behind the immunological advantage of females, may
      also affect X-linked microRNAs. The human X chromosome contains 10% of all
      microRNAs detected so far in the human genome. Although the role of most of them
      has not yet been described, several X chromosome-located microRNAs have important
      functions in immunity and cancer. We therefore provide a detailed map of all
      described microRNAs located on human and mouse X chromosomes, and highlight the
      ones involved in immune functions and oncogenesis. The unique mode of inheritance
      of the X chromosome is ultimately the cause of the immune disadvantage of males
      and the enhanced survival of females following immunological challenges. How
      these aspects influence X-linked microRNAs will be a challenge for researchers in
      the coming years, not only from an evolutionary point of view, but also from the
      perspective of disease etiology.

PMID- 21953568
TI  - Identification of genomic aberrations associated with disease transformation by
      means of high-resolution SNP array analysis in patients with myeloproliferative
      neoplasm.
AB  - Myeloproliferative neoplasms (MPN) include polycythemia vera (PV), essential
      thrombocythemia (ET), and primary myelofibrosis (PMF). These disorders may
      undergo phenotypic shifts, and may specifically evolve into secondary
      myelofibrosis (MF) or acute myeloid leukemia (AML). We studied genomic changes
      associated with these transformations in 29 patients who had serial samples
      collected in different phases of disease. Genomic DNA from granulocytes, i.e.,
      the myeloproliferative genome, was processed and hybridized to genome-wide human
      SNP 6.0 arrays. Most patients in chronic phase had chromosomal regions with
      uniparental disomy (UPD) and/or copy number changes. Disease progression to
      secondary MF or AML was associated with the acquisition of additional chromosomal
      aberrations in granulocytes (P = 0.002). A close relationship was observed
      between aberrations of chromosome 9p (UPD and/or gain) and progression from PV to
      post-PV MF (P = 0.002). The acquisition of one or more aberrations involving
      chromosome 5, 7, or 17p was specifically associated with progression to AML (OR
      5.9, 95% CI 1.2-27.7, P = 0.006), and significantly affected overall survival (HR
      18, 95% CI 1.9-164, P = 0.01). These observations indicate that disease
      progression from chronic-phase MPN to secondary MF or AML is associated with
      specific chromosomal aberrations that can be detected by means of high-resolution
      SNP array analysis of granulocyte DNA.

PMID- 21953570
TI  - Exogenous mammalian sex hormones mitigate inhibition in growth by enhancing
      antioxidant activity and synthesis reactions in germinating maize seeds under
      salt stress.
AB  - BACKGROUND: Mammalian sex hormones (MSH)-progesterone, beta-estradiol and
      androsterone-enhance plant growth and development by stimulating significant
      morphological and biochemical parameters under normal conditions. However, there
      is no report regarding their effects on plants exposed to environmental stress
      conditions. Therefore, the present study was focused on elucidating the possible
      positive effects of MSH on seedling growth, antioxidant activity and synthesis
      reactions in maize seeds exposed to salt stress, one of the most important
      environmental stresses. For this purpose, the various concentrations (10-6, 10-8,
      10-10 and 10-12 mol L-1) of MSH were studied. RESULTS: Salinity (100 mmol L-1
      NaCl) significantly reduced root length and seedling height, whereas MSH
      treatment significantly ameliorated the adverse effects of salinity on root
      length and seedling height. On the other hand, although salinity increased
      soluble protein, soluble sugar and proline content in 7-day-old maize seedlings,
      these were higher in MSH-treated seedlings. Similarly, MSH treatment augmented
      superoxide dismutase, peroxidase and catalase activities under salt stress,
      whereas it decreased superoxide production and lipid peroxidation level. The most
      favorable concentrations were determined as 10-8 mol L-1 for progesterone and
      beta-estradiol and 10-10 mol L-1 for androsterone. CONCLUSION: Exogenous MSH
      application was found to have an important ameliorative effect on growth of seeds
      exposed to salt stress by stimulating antioxidant activity and synthesis
      reactions. This is the first study investigating the effects of MSH on
      germination of seeds exposed to stress conditions.

PMID- 21953571
TI  - Clinical implications of pathophysiological and demographic covariates on the
      population pharmacokinetics of trastuzumab emtansine, a HER2-targeted antibody
      drug conjugate, in patients with HER2-positive metastatic breast cancer.
AB  - Trastuzumab emtansine (T-DM1) is a HER2-targeted antibody-drug conjugate in
      development for treatment of HER2-positive cancers. T-DM1 has been tested as a
      single agent in a phase I and 2 phase II studies of patients with heavily
      pretreated metastatic breast cancer (MBC), with the maximum tolerated dose
      established at 3.6 mg/kg intravenously for every-3-week dosing. The authors
      present results from the population pharmacokinetics analysis for T-DM1.
      Population pharmacokinetics for T-DM1 were characterized using a clinical
      database of 273 patients from the 3 studies. Pharmacokinetics was best described
      by a linear 2-compartment model. Population estimates (interindividual
      variability [IIV]) for pharmacokinetic parameters were clearance, 0.7 L/d
      (21.0%); central compartment volume (V(c)), 3.33 L (13.2%); peripheral
      compartment volume (V(p)), 0.89 L (50.4%); and intercompartmental clearance, 0.78
      L/d. Body weight, albumin, tumor burden, and aspartate aminotransferase levels
      were identified as statistically significant covariates accounting for
      interindividual variability in T-DM1 pharmacokinetics, with body weight having a
      greater effect on IIV of clearance and V(c) than other covariates. T-DM1 exposure
      was relatively consistent across the weight range following body weight-based
      dosing. This analysis suggests no further T-DM1 dose adjustments are necessary in
      heavily pretreated patients with MBC.

PMID- 21953572
TI  - Tigecycline pharmacokinetics in subjects with various degrees of renal function.
AB  - The pharmacokinetic parameters of tigecycline were assessed in subjects with
      severe renal impairment (creatinine clearance <30 mL/min, n = 6), subjects
      receiving hemodialysis (4 received tigecycline before and 4 received tigecycline
      after hemodialysis), and subjects with age-adjusted, normal renal function (n =
      6) after administration of single 100-mg doses. Serial serum and urine samples
      were collected and assayed using validated liquid chromatography with tandem mass
      spectrometer (LC/MS/MS) methods. Concentration-time data were then analyzed using
      noncompartmental pharmacokinetic methods. Tigecycline renal clearance in subjects
      with normal renal function represented approximately 20% of total systemic
      clearance. Tigecycline clearance was reduced by approximately 20%, and area under
      the tigecycline concentration-time curve increased by approximately 30% in
      subjects with severe renal impairment. Tigecycline was not efficiently removed by
      dialysis; thus, it can be administered without regard to timing of hemodialysis.
      Based on these pharmacokinetic data, tigecycline requires no dosage adjustment in
      patients with renal impairment.

PMID- 21953573
TI  - Beneficial effect of vardenafil on aortic stiffness and wave reflections.
AB  - Although vardenafil is widely prescribed for erectile dysfunction (ED), its
      effect on arterial function is not defined. Aortic stiffness, aortic pressures,
      and wave reflections are predictors of cardiovascular risk. The investigators
      assessed the hypothesis that vardenafil acutely improves aortic stiffness, aortic
      pressures, and wave reflections in ED patients. Twelve ED patients (mean age 58
      +/- 9 years) received vardenafil 20 mg in a randomized, placebo-controlled,
      double-blind, 2-way crossover design. Aortic stiffness was evaluated with carotid
      femoral pulse wave velocity (PWV); wave reflections and aortic pressures were
      evaluated with augmentation index (AIx) and systolic, diastolic, and pulse
      pressure of the aortic pressure waveform, respectively. PWV, aortic pressures,
      and AIx were measured at baseline and for 3 hours after vardenafil intake or
      placebo. PWV decreased significantly (by 0.7 m/s, P = .001), denoting a decrease
      in aortic stiffness. AIx decreased significantly (by 7%, P = .008), denoting a
      decreased effect of wave reflections from the periphery. Aortic pressures
      decreased significantly (all P < .05). Statin use at baseline significantly
      interacted with the effects of treatment on both PWV and AIx (P = .003 and P <
      .001, respectively). This study shows, for the first time, that vardenafil has a
      favorable acute effect on aortic stiffness and wave reflection in ED patients.

PMID- 21953574
TI  - Fixed drug eruption: levofloxacin, another culprit drug.

PMID- 21953575
TI  - An experimental study on MR imaging of atherosclerotic plaque with SPIO marked
      endothelial cells in a rabbit model.
AB  - PURPOSE: To investigate how to label macrophages in atherosclerotic plaques with
      superparamagnetic iron oxide (SPIO) nanoparticles and trace SPIO with MR imaging.
      MATERIALS AND METHODS: Atherosclerotic lesions of a rabbit model were induced by
      a combination of high-fat and high-cholesterol diet and subsequent endothelial
      abrasion of the abdominal aorta. SPIO particles were pretreated with poly-L
      lysine. SPIO nanoparticles and SPIO-labeled human endothelial cells (ECV-304)
      were IV injected into model animals, respectively. The MRI scans and
      histopathological examination were performed 12 h and 24 h after the injection.
      The imaging and histopathological data were analyzed. RESULTS: Prussian blue
      staining of the vessel specimens indicated that SPIO particles were not found in
      the atheroma but in the Kupffer's cells of the liver after SPIO injection.
      However, the accumulation of SPIO particles in the atheroma was confirmed in
      animals received SPIO-labeled endothelial cell transplantation. The best quality
      MR scan sequences of rabbit abdominal aorta were T(2) WI fat suppression, T(1)
      WI, and DIR series, on which of MR image had a higher quality. Signal loss of the
      original incrassate plaque in the vessel wall on T(2) WI was found in 6 of 10
      animals received SPIO-labeled endothelial cell transplantation. CONCLUSION: SPIO
      labeled endothelial cells were superior to SPIO for MR imaging of atherosclerotic
      plaques.

PMID- 21953576
TI  - The synthesis and coating of long, thin copper nanowires to make flexible,
      transparent conducting films on plastic substrates.

PMID- 21953577
TI  - Increases of pentraxin 3 plasma levels in patients with Parkinson's disease.
AB  - Pentraxin 3 is a prototypic long pentraxin. Pentraxin 3 is a soluble recognition
      receptor that is involved in innate immunity and the inflammatory response. Its
      expression is induced by proinflammatory signals. The aim of this study was to
      compare the plasma levels of pentraxin 3 in healthy subjects and patients with
      neurodegenerative disorders such as mild cognitive impairment, Alzheimer's
      disease, and Parkinson's disease (PD). Thirty-nine patients with mild cognitive
      impairment, 75 patients with Alzheimer's disease, 66 patients with PD, and 41
      healthy elderly controls were recruited for this study. We performed an extensive
      battery of neuropsychological tests, including a Mini-Mental Status Examination,
      clinical dementia rating, and the Unified Parkinson's Disease Rating Scale. A
      variety of clinical information was collected from the administered
      semistructured questionnaire. Plasma pentraxin 3 levels were measured using a
      specific enzyme-linked immunosorbent assay. Plasma pentraxin 3 levels were
      significantly higher in the PD patients than in the patients with mild cognitive
      impairment and Alzheimer's disease and in the control subjects. Plasma pentraxin
      3 levels in the PD patients were correlated with activities of daily living (r =
      0.368; P = .003) and motor function (r = 0.358; P = .004). Plasma pentraxin 3
      levels could be a new biochemical marker for PD, and they may be associated with
      the severity of motor dysfunction and other clinical symptoms in PD patients.

PMID- 21953579
TI  - Painless legs and moving toes: symptom reduction during pregnancy.

PMID- 21953578
TI  - A randomized trial of internet-based versus traditional sexual counseling for
      couples after localized prostate cancer treatment.
AB  - BACKGROUND: After treatment for prostate cancer, multidisciplinary sexual
      rehabilitation involving couples appears more promising than traditional urologic
      treatment for erectile dysfunction (ED). The authors of this report conducted a
      randomized trial comparing traditional or internet-based sexual counseling with
      waitlist (WL) control. METHODS: Couples were randomized adaptively to a 3-month
      WL, a 3-session face-to-face format (FF), or an internet-based format (WEB1). A
      second internet-based group (WEB2) was added to examine the relation between web
      site use and outcomes. At baseline, post-WL, post-treatment, and 6-month, and 12
      month follow-up assessments, participants completed the International Index of
      Erectile Function (IIEF), the Female Sexual Function Index (FSFI), the Brief
      Symptom Inventory-18 to measure emotional distress, and the abbreviated Dyadic
      Adjustment Scale. RESULTS: Outcomes did not change during the WL period. Of 115
      couples that were randomized to FF or WEB1 and 71 couples in the WEB2 group, 34%
      dropped out. Neither drop-outs nor improvements in outcomes differed
      significantly between the 3 treatment groups. In a linear mixed-model analysis
      that included all participants, mean +/- standard deviation IIEF scores improved
      significantly across time (baseline, 29.7 +/- 17.9; 12 months, 36.2 +/- 22.4; P <
      .001). FSFI scores also improved significantly (baseline, 15.4 +/- 8.5; 12
      months, 18.2 +/- 10.7; P = .034). Better IIEF scores were associated with finding
      an effective medical treatment for ED and normal female sexual function at
      baseline. In the WEB2 group, IIEF scores improved significantly more in men who
      completed >75% of the intervention. CONCLUSIONS: An internet-based sexual
      counseling program for couples was as effective as a brief, traditional sex
      therapy format in producing enduring improvements in sexual outcomes after
      prostate cancer.

PMID- 21953580
TI  - Subdiaphragmatic vagotomy induces a functional change in visceral Adelta primary
      afferent fibers in rats.
AB  - Vagal nerves modulate not only physical homeostasis, but also pain transmission.
      It has been reported that subdiaphragmatic vagal dysfunction causes visceral
      pain. However, the functional changes in nociceptive primary afferent fibers
      under such visceral pain soon after subdiaphragmatic vagal dysfunction are not
      fully documented. The present study was designed to investigate changes in the
      sensitivity of primary afferent fibers in the distal colon using a Neurometer
      which individually stimulates C, Adelta and Abeta fibers. Under stimulation with
      a handmade stimulus electrode in the distal colon, the current threshold in the
      distal colon was recorded with high reproducibility. Subdiaphragmatic vagotomy
      significantly decreased the current threshold of Adelta fibers in the distal
      colon with no change in the sensitivity of C or Abeta fibers. These results
      suggest that vagal dysfunction at an early stage may cause, at least in part,
      hypersensitivity of visceral Adelta fibers.

PMID- 21953581
TI  - Persistent sensitization of depressive-like behavior and thermogenic response
      during maternal separation in pre- and post-weaning guinea pigs.
AB  - Early attachment disruption is thought to promote later onset of depressive
      illness through a process involving sensitization. Maternal separation in guinea
      pig pups produces depressive-like behavior and core body temperature fluctuations
      that appear to be mediated by proinflammatory activity. In pups near the age of
      weaning (~20 days of age), these responses are increased during repeated
      separations occurring over several days. Here, enhanced depressive-like behavior
      and core body temperature responses were observed during repeated separations in
      guinea pigs from ~10 to 30 days of age. The sensitization lasted for more than a
      week, with the greatest temperature response occurring during the final
      separation. These results demonstrate persisting sensitization of behavioral and
      thermogenic responses to maternal separation over the age range in which these
      responses are known to occur. The findings are consistent with the hypothesis
      that proinflammatory activity contributes to the sensitization response and
      provide further suggestion that the impact of early attachment disruption on
      susceptibility to depression may involve proinflammatory processes.

PMID- 21953582
TI  - HLA-E/beta2 microglobulin overexpression in colorectal cancer is associated with
      recruitment of inhibitory immune cells and tumor progression.
AB  - The host immune response plays a major role in colorectal carcinoma (CRC)
      progression. A mechanism of tumor immune escape might involve expression of the
      human leucocyte antigen (HLA)-E/beta2m on tumor cells. The inhibitory effect of
      HLA-E/beta2m on CD8+ cytotoxic T lymphocytes and natural killer (NK) cells is
      mediated by the main HLA-E receptor CD94/NKG2A. As the pathophysiological
      relevance of this mechanism in CRC remains unknown, this prompted us to examine,
      in situ, in a series of 80 CRC (i) the HLA-E and beta2m coexpression by tumor
      cells, (ii) the density of CD8+, cytotoxic, CD244+ and NKP46+ intraepithelial
      tumor-infiltrating lymphocyte (IEL-TIL) and (iii) the expression of CD94/NKG2
      receptor on IEL-TIL. These data were then correlated to patient survival. We
      provided (i) the in situ demonstration of HLA-E/beta2m overexpression by tumor
      cells in 21% of CRC characterized by an overrepresentation of signet ring cell
      carcinomas, mucinous carcinomas and medullary carcinomas, (ii) the significant
      association between HLA-E/beta2m overexpression by tumor cells and increased
      density of CD8+ cytotoxic, CD244+ and CD94+ IEL-TIL and (iii) finally, the
      unfavorable prognosis associated with HLA-E/beta2m overexpression by tumor cells.
      Our findings show that HLA-E/beta2m overexpression is a surrogate marker of poor
      prognosis and point to a novel mechanism of tumor immune escape in CRC in
      restraining inhibitory IEL-TIL.

PMID- 21953583
TI  - CXCL12gamma isoform is expressed on endothelial and dendritic cells in rheumatoid
      arthritis synovium and regulates T cell activation.
AB  - OBJECTIVE: CXCL12gamma is an alternative splicing isoform of CXCL12 with enhanced
      affinity for heparan sulfate (HS) proteoglycans. This study was undertaken to
      investigate the distribution and potential function of CXCL12gamma in rheumatoid
      arthritis (RA) synovium and normal lymphoid tissue, where its immobilization to
      HS may be relevant in pathologic or homeostatic immune cell migration and
      activation. METHODS: Expression of CXCL12 or CXCL12gamma was immunodetected in RA
      and normal synovium, lymphoid tissue, and cultured cells with anti-pan-CXCL12 or
      anti-CXCL12gamma-specific monoclonal antibodies. CXCL12alpha and CXCL12gamma
      messenger RNA expression was analyzed by quantitative reverse transcription
      polymerase chain reaction. Binding of wild-type CXCL12 isoforms or their HS
      binding-defective mutants to monocyte-derived dendritic cells (DCs) was analyzed
      by flow cytometry. The effect of DC-bound CXCL12alpha and CXCL12gamma on T cell
      activation was analyzed in DC/T cell allogeneic cultures. RESULTS: CXCL12gamma
      expression was increased in RA compared to normal synovium and preferentially
      located in endothelia and DC-SIGN-positive cells. This distribution was also
      observed in lymphoid organs. Surface-bound CXCL12gamma was detected in a fraction
      of freshly isolated DCs. Monocyte-derived DCs, but not monocytes, showed a high
      capacity to bind CXCL12gamma in an HS-dependent manner. Surface-bound CXCL12alpha
      and CXCL12gamma on monocyte-derived DCs were potent inhibitors of allogeneic T
      cell activation, in contrast to the T cell-stimulatory effects of soluble CXCL12
      proteins. CONCLUSION: CXCL12gamma shows a specific and similar distribution in RA
      synovium and lymphoid tissue, consistent with its higher HS binding affinity.
      Presentation of CXCL12 to T cells on membrane HS in DCs can play a distinct
      regulatory role in T cell activation.

PMID- 21953584
TI  - The antidepressant citalopram inhibits delayed rectifier outward K+ current in
      mouse cortical neurons.
AB  - Citalopram, a selective serotonin (5-HT) reuptake inhibitor (SSRI) as well as an
      antidepressant, is thought to exert its effects by increasing synaptic 5-HT
      levels. However, few studies have addressed the possibility that citalopram has
      other molecular mechanisms of action. We examined the effects of citalopram on
      delayed rectifier outward K(+) current (I(K) ) in mouse cortical neurons.
      Extracellular citalopram reversibly inhibited I(K) in a dose-dependent manner and
      significantly shifted both steady-state activation and inactivation curves toward
      hyperpolarization. Neither 5-HT itself nor antagonists of 5-HT and dopamine
      receptors could abolish citalopram-induced inhibition of I(K) . In addition,
      intracellular application of GTPgamma-S similarly failed to prevent the
      inhibition of I(K) by citalopram. When applied intracellularly, citalopram had no
      effect on I(K) and did not influence the reduction of I(K) induced by
      extracellular citalopram. The effect of citalopram was use dependent, but not
      frequency dependent, and it did not require channel opening. Electrophysiological
      recordings in acute cortical slice showed that citalopram significantly reduced
      the action potential (AP) firing frequency of cortical neurons and increased
      action potential duration (APD). The selective Kv2.1 subunit blocker
      Jingzhaotoxin-III (JZTX-III) did not abolish citalopram-induced I(K) inhibition.
      Transfection of HEK293 cells with Kv2.1 or Kv2.2 constructs indicated that
      citalopram mainly inhibited Kv2.2 current. We suggest that citalopram-induced
      inhibition of I(K) in mouse cortical neurons is independent of G-protein-coupled
      receptors and might exert its antidepressant effects by enhancing presynaptic
      efficiency. Our results may help to explain some of the unknown therapeutic
      effects of citalopram.

PMID- 21953585
TI  - External-energy-independent polymer capsule motors and their cooperative
      behaviors.
AB  - The design and development of mobile nano-, micro-, and millimeter-scale
      autonomous systems have been perused over several decades. Here, we introduce a
      millimeter-sized polymer capsule motor with specific features and
      functionalities. It runs without any external energy sources or the consumption
      of external fuels such as H(2)O(2) or glucose. The occurrence of motion is due to
      the asymmetric release of organic solvent from the capsule and the asymmetric
      change in the surface tension of the surrounding liquid. The capsule moves from a
      place of lower surface tension to a place of higher surface tension (Marangoni
      effect) in an attempt by the system to attain the desirable lowest-free-energy
      state. The operation of the motor is versatile in terms of the environment, as it
      moves on a wide variety of liquid/air interfaces, including water, sea water,
      organic solvent/water mixtures, and acids. A high-motion velocity was observed,
      with a travelling distance of over 20 meters. The manipulation of its motion was
      achieved upon functionalization with nickel powder and application of an external
      magnetic field. Long-range interaction behaviors and surface-cleaning effects due
      to the chemotaxis effect were also demonstrated when the capsule was
      functionalized with sodium dodecyl sulfate (SDS). We believe that a plethora of
      applications can be envisioned with this motor, such as cargo delivery,
      manipulation of matter, sensing and detection, biorecognition, and environmental
      remediation.

PMID- 21953586
TI  - Proteomic analysis of arsenite - mediated multiple antibiotic resistance in
      Yersinia enterocolitica biovar 1A.
AB  - Arsenic is one of the most important global environmental pollutants. In the
      present study, fifty one clinical strains of Yersinia enterocolitica biovar 1A
      showed high resistance to arsenite and arsenate. The minimum inhibitory
      concentration (MIC) of arsenite (0.625-20 mM) was lower than arsenate (10-80 mM).
      Growth of Y. enterocolitica in 2 mM arsenite led to 2-8 fold increase in MICs of
      the five antibiotics (amikacin, ciprofloxacin, gentamycin, kanamycin and
      tetracycline), suggesting expression of arsenite-induced multiple antibiotic
      resistance among the strains. Proteomic analysis of Y. enterocolitica revealed
      differential expression of certain proteins following arsenite exposure, which
      included a putative outer membrane porin (OmpA) and a putative amino acid
      transporter protein. In conclusion, modulation of membrane permeability may be
      involved in the induction of arsenite-mediated expression of multiple antibiotic
      resistance in Y. enterocolitica.

PMID- 21953587
TI  - Evidence for the presence of proteolytically active secreted aspartic proteinase
      1 of Candida parapsilosis in the cell wall.
AB  - Pathogenic yeasts of the genus Candida produce secreted aspartic proteinases,
      which are known to enhance virulence. We focused on Sapp1p proteinase secreted by
      Candida parapsilosis and studied the final stage of its passage through the cell
      wall and release into the extracellular environment. We found that Sapp1p
      displays enzyme activity prior to secretion, and therefore, it is probably fully
      folded within the upper layer of the cell wall. The positioning of cell surface
      associated Sapp1p was detected by cell wall protein labeling using biotinylation
      agents, extraction of cell wall proteins by beta-mercaptoethanol, immunochemical
      detection, and mass spectrometry analysis. All lysine residues present in the
      structure of soluble, purified Sapp1p were labeled with biotin. In contrast, the
      accessibility of individual lysines in cell wall-associated Sapp1p varied with
      the exception of four lysine residues that were biotinylated in all experiments
      performed, suggesting that Sapp1p has a preferred orientation in the cell wall.
      As the molecular weight of this partially labeled Sapp1p did not differ among the
      experiments, we can assume that the retaining of Sapp1p in the cell wall is not a
      totally random process and that pathogenic yeasts might use this cell-associated
      proteinase activity to enhance degradation of appropriate substrates.

PMID- 21953588
TI  - Hepatocellular carcinoma confirmation, treatment, and survival in surveillance,
      epidemiology, and end results registries, 1992-2008.
AB  - Approaches to the diagnosis and management of hepatocellular carcinoma (HCC) are
      improving survival. In the Surveillance, Epidemiology, and End Results-13
      registries, HCC stage, histological confirmation, and first-course surgery were
      examined. Among 21,390 HCC cases diagnosed with follow-up of vital status during
      1998-2008, there were 4,727 (22%) with reported first-course invasive liver
      surgery, local tumor destruction, or both. The proportion with reported liver
      surgery or ablation was 39% among localized stage cases and only 4% among
      distant/unstaged cases. Though 70% of cases had histologically confirmed
      diagnoses, the proportion with confirmed diagnoses was higher among cases with
      reported invasive surgery (99%), compared to cases receiving ablation (81%) or no
      reported therapy (65%). Incidence rates of histologically unconfirmed HCC
      increased faster than those of confirmed HCC from 1992 to 2008 (8% versus 3% per
      year). Two encouraging findings were that incidence rates of localized-stage HCC
      increased faster than rates of regional- and distant-stage HCC combined (8%
      versus 4% per year), and that incidence rates of reported first-course surgery or
      tumor destruction increased faster than incidence rates of HCC without such
      therapy (11% versus 7%). Between 1975-1977 and 1998-2007, 5-year cause-specific
      HCC survival increased from just 3% to 18%. Survival was 84% among transplant
      recipients, 53% among cases receiving radiofrequency ablation at early stage, 47%
      among cases undergoing resection, and 35% among cases receiving local tumor
      destruction. Asian or Pacific Islander cases had significantly better 5-year
      survival (23%) than white (18%), Hispanic (15%), or black cases (12%).
      CONCLUSION: HCC survival is improving, because more cases are diagnosed and
      treated at early stages. Additional progress may be possible with continued use
      of clinical surveillance to follow individuals at risk for HCC, enabling early
      intervention.

PMID- 21953589
TI  - Metabolic effects of high-dose prednisolone treatment in early rheumatoid
      arthritis: balance between diabetogenic effects and inflammation reduction.
AB  - OBJECTIVE: To investigate the dose-related effects of glucocorticoid treatment on
      glucose tolerance, beta cell function, and insulin sensitivity in patients with
      early active rheumatoid arthritis (RA). METHODS: A randomized, controlled, single
      blind trial was conducted in 41 patients with early active RA. At the beginning
      of the trial patients had not been treated for their RA, and were randomized to
      begin treatment with prednisolone at 60 mg/day or 30 mg/day. Before and at the
      end of 1 week of treatment, a frequently sampled oral glucose tolerance test was
      performed. The glucose area under the curve (AUC(G) ) was calculated. In
      addition, beta cell function and insulin sensitivity parameters were computed.
      RESULTS: Patients (mean +/- SD age 55.5 +/- 14.8 years and 54.2 +/- 12.6 years in
      the prednisone 60 mg/day and prednisone 30 mg/day groups, respectively; body mass
      index 24.5 +/- 4.1 kg/m(2)  and 25.4 +/- 4.2 kg/m(2) , respectively) had active
      disease at baseline (mean +/- SD Disease Activity Score in 44 joints 4.1 +/- 0.7
      and 4.0 +/- 0.8, respectively; median C-reactive protein [CRP] level 14 mg/liter
      [interquartile range 6-34] and 19 mg/liter [interquartile range 3-39],
      respectively). In addition, 56% of the patients had impaired glucose tolerance at
      baseline, and 7% were found to have previously unrecognized type 2 diabetes
      mellitus (DM). Associations of the AUC(G)  with erythrocyte sedimentation rate
      (beta = 2.430 [95% confidence interval 0.179-4.681], P = 0.04) and with CRP level
      (beta = 2.358 [95% confidence interval 0.210-4.506], P = 0.03) were demonstrated.
      Treatment with prednisolone at both dosages reduced CRP levels significantly. The
      incidence of type 2 DM increased to 24% (P < 0.001) (evenly distributed across
      the groups). The mean AUC(G)  did not change in either treatment arm. Beta cell
      function improved during prednisone treatment at 60 mg/day (P = 0.02) and at 30
      mg/day (P = 0.04). Disease duration was associated with changes in the AUC(G) 
      (beta = 3.626 [95% confidence interval 1.077-6.174], P = 0.007) and with
      deterioration of the glucose state (odds ratio 1.068 [95% confidence interval
      1.017-1.122], P = 0.009). CONCLUSION: In this study, short-term treatment with
      prednisolone 60 mg or 30 mg per day improved disease activity without
      deterioration of glucose tolerance in patients with active RA. However, due to
      individual differences, monitoring is recommended.

PMID- 21953590
TI  - Differential sensitivity of specific neuronal populations of the rat hypothalamus
      to prolactin action.
AB  - Prolactin stimulates dopamine release from neuroendocrine dopaminergic (NEDA)
      neurons in the hypothalamic arcuate nucleus (ARC) to maintain low levels of serum
      prolactin. Elevated prolactin levels during pregnancy and lactation may mediate
      actions in other hypothalamic regions such as the paraventricular nucleus (PVN)
      and rostral preoptic area (rPOA). We predicted that NEDA neurons would be more
      sensitive prolactin targets than neurons in other regions because they are
      required to regulate basal prolactin secretion. Moreover, differences in the
      accessibility of the ARC to prolactin in blood may influence the responsiveness
      of this population. Therefore, we compared prolactin-induced signaling in
      different hypothalamic neuronal populations following either systemic or
      intracerebroventricular (icv) prolactin administration. Phosphorylation of the
      signal transduction factor, STAT5 (pSTAT5), was used to identify prolactin
      responsive neurons. In response to systemic prolactin, pSTAT5-labeled cells were
      widely observed in the ARC but absent from the rPOA and PVN. Many of these
      responsive cells in the ARC were identified as NEDA neurons. The lowest icv
      prolactin dose (10 ng) induced pSTAT5 in the ARC, but with higher doses (>500 ng)
      pSTAT5 was detected in numerous regions, including the rPOA and PVN. NEDA neurons
      were maximally labeled with nuclear pSTAT5 in response to 500 ng prolactin and
      appeared to be more sensitive than dopaminergic neurons in the rPOA.
      Subpopulations of oxytocin neurons in the hypothalamus were also found to be
      differentially sensitive to prolactin. These data suggest that differences in the
      accessibility of the arcuate nucleus to prolactin, together with intrinsic
      differences in the NEDA neurons, may facilitate homeostatic feedback regulation
      of prolactin release.

PMID- 21953591
TI  - Tissue interaction is required for glenoid fossa development during
      temporomandibular joint formation.
AB  - The mammalian temporomandibular joint (TMJ) develops from two distinct
      mesenchymal condensations that grow toward each other and ossify through
      different mechanisms, with the glenoid fossa undergoing intramembranous
      ossification while the condyle being endochondral in origin. In this study, we
      used various genetically modified mouse models to investigate tissue interaction
      between the condyle and glenoid fossa during TMJ formation in mice. We report
      that either absence or dislocation of the condyle results in an arrested glenoid
      fossa development. In both cases, glenoid fossa development was initiated, but
      failed to sustain, and became regressed subsequently. However, condyle
      development appears to be independent upon the presence of the forming glenoid
      fossa. In addition, we show that substitution of condyle by Meckel's cartilage is
      able to sustain glenoid fossa development. These observations suggest that proper
      signals from the developing condyle or Meckel's cartilage are required to sustain
      the glenoid fossa development.

PMID- 21953593
TI  - Development of bone-targeted catalase derivatives for inhibition of bone
      metastasis of tumor cells in mice.
AB  - Removal of hydrogen peroxide by delivering catalase to the vicinity of
      metastasizing tumor cells is a promising approach for inhibiting tumor
      metastasis. To inhibit bone metastasis, catalase was conjugated with 3,5
      di(ethylamino-2,2-bisphosphono)benzoic acid (Bip), a derivative of bone-seeking
      bisphosphonates, polyethylene glycol (PEG), or both. Bip-conjugated catalase
      derivatives, that is, catalase-Bip and PEG-catalase-Bip, exhibited a higher
      affinity for bone matrix as compared with their counterparts without Bip. The
      tissue distribution of (111) In-labeled catalase derivatives indicated that the
      accumulation of radioactivity in bones was increased by conjugation of either Bip
      or PEG with catalase. An experimental bone metastasis model was developed by
      injecting male C57BL/6 mice with murine melanoma B16-BL6/Luc cells, which stably
      express firefly luciferase into left ventricle. Repeated injections of catalase
      to tumor-bearing mice had no significant effect on the number of melanoma cells
      in tibiae and femurs, whereas injections of catalase-Bip, PEG-catalase, or PEG
      catalase-Bip significantly reduced the number. These results indicate that
      targeted delivery of catalase to the bones can be achieved by conjugating the
      enzyme with either Bip or PEG, and this delivery is effective in inhibiting the
      bone metastasis of tumor cells.

PMID- 21953594
TI  - Clinical and molecular characterization of limb-girdle muscular dystrophy due to
      LAMA2 mutations.
AB  - INTRODUCTION: In this study we describe the clinical and molecular
      characteristics of limb-girdle muscular dystrophy (LGMD) due to LAMA2 mutations.
      METHODS: Five patients clinically diagnosed with LGMD and showing brain white
      matter hyperintensities on MRI were evaluated using laminin alpha2 genetic and
      protein testing. RESULTS: The patients had slowly progressive, mild muscular
      dystrophy with various degrees of CNS involvement. Epilepsy was observed in 2,
      and subtle symptoms of CNS involvement (mild deficit in executive functions and
      low IQ scores) were noted in 3 patients. Novel LAMA2 mutations were identified in
      all patients. The amount of laminin alpha2 protein in the muscle biopsies ranged
      from trace to about 50% compared with controls. CONCLUSIONS: This study
      represents the largest series of LGMD laminin alpha2-deficient patients and
      expands the clinical phenotype associated with LAMA2 mutations. The findings
      suggest that brain MRI could be included in the diagnostic work-up of patients
      with undiagnosed LGMD.

PMID- 21953592
TI  - Immune regulation in chronically transfused allo-antibody responder and
      nonresponder patients with sickle cell disease and beta-thalassemia major.
AB  - Red blood cell alloimmunization is a major complication of transfusion therapy.
      Host immune markers that can predict antibody responders remain poorly described.
      As regulatory T cells (Tregs) play a role in alloimmunization in mouse models, we
      analyzed the Treg compartment of a cohort of chronically transfused patients with
      sickle cell disease (SCD, n = 22) and beta-thalassemia major (n = 8) with and
      without alloantibodies. We found reduced Treg activity in alloantibody responders
      compared with nonresponders as seen in mice. Higher circulating anti-inflammatory
      IL-10 levels and lower IFN-gamma levels were detected in non-alloimmunized SCD
      patients. Stimulated sorted CD4+ cells from half of the alloimmunized patients
      had increased frequency of IL-4 expression compared with nonresponders,
      indicating a skewed T helper (Th) 2 humoral immune response in a subgroup of
      antibody responders. All patients had increased Th17 responses, suggesting an
      underlying inflammatory state. Although small, our study indicates an altered
      immunoregulatory state in alloantibody responders which may help future
      identification of potential molecular risk factors for alloimmunization.

PMID- 21953595
TI  - Implications of X-linked gene regulation for sex differences in disease
      pathogenesis (comment on DOI 10.1002/bies.201100047).

PMID- 21953596
TI  - The effect of structure and phase transformation on the mechanical properties of
      Re2N and the stability of Mn2N.
AB  - First-principles calculations were carried out on recently synthesized Re2N and
      Re3N as well as hypothetical Tc and Mn nitrides. It is found that structure and
      covalent bonds play an important role in determining mechanical properties. Under
      a large strain along (0001)<1010> direction, Re2N undergoes a phase
      transformation with a slight increase in ideal shear strength. On the other hand,
      it is transformed into a phase with weaker mechanical properties, if the strain
      is along Re2 <1210> direction. Mn2N can be synthesized under moderate conditions
      due to its more negative formation energy. Re2N, Re3N, and Mn2 N show structure
      related mechanical property under larger strains to ReB2 but exhibit much lower
      ideal strengths, which is attributed to the larger ionicity of cation-anion bond.
      Three-dimensional framework of strong covalent bonds is thus highly recommended
      to design superhard materials.

PMID- 21953597
TI  - Bioconcentration of methylmercury in microzooplankton in a temperate river.
AB  - To understand the bioconcentration of methylmercury (MeHg) at the base of the
      riverine food chain, we determined levels of dissolved organic carbon,
      microseston, Hg, and MeHg in surface water in relation to the microzooplankton
      MeHg from Yeongsan River. The spatial distribution of unfiltered Hg (0.29-3.1
      ng/L) and dissolved Hg (0.15-0.74 ng/L) closely followed the microseston
      distribution. The spatial distribution of unfiltered MeHg (0.0078-0.077 ng/L) and
      dissolved MeHg (0.0069-0.018 ng/L) increased with increasing distance from the
      river mouth and appeared to arise from the shallow wetlands surrounding the upper
      riverbanks and then to be transported downstream. The logarithm of the MeHg
      bioconcentration factor for microzooplankton ranged from 5.3 to 6.0 (5.7 +/-
      0.18), and for microseston ranged from 4.0 to 5.4 (4.9 +/- 0.35). Linear
      correlation statistics comparing microzooplankton MeHg and river water
      characteristics revealed that microzooplankton MeHg concentration was most
      significantly correlated with unfiltered MeHg (r = 0.83) and particulate MeHg (r
      = 0.80) levels. This result suggests that MeHg in unfiltered river water, which
      is relatively easy to determine, can be used as a surrogate for MeHg in
      microzooplankton that may influence MeHg levels in higher-trophic-level
      organisms.

PMID- 21953598
TI  - Quality assessment of tomato landraces and virus-resistant breeding lines: quick
      estimation by near infrared reflectance spectroscopy.
AB  - BACKGROUND: Several tomato landraces are very popular in south-eastern Spain for
      their organoleptic fruit quality, but these cultivars are highly susceptible to
      several viruses. A breeding programme is being carried out for the introduction
      of virus resistances into these landraces. In the last steps of our breeding
      programme a high number of breeding lines must be evaluated for agronomic and
      organoleptic quality parameters. Near infrared reflectance spectroscopy (NIRS)
      technology shows considerable promise and is ideally suited to the requirements
      of breeders. RESULTS: Significant differences between a set of 35 tomato breeding
      lines, seven landraces and one commercial hybrid were observed for quality and
      mineral content parameters, suggesting that there are considerable levels of
      genetic diversity between the cultivar groups studied. Using NIRS on dry samples
      of tomato constitutes a feasible technique to estimate the content of several
      minerals (C, N, P, K, Ca, Na, Mn, Mg and Cu) according to the coefficient of
      determination for calibration (R(2) > 0.90). NIRS estimations of soluble solids
      content and titratable acidity obtained were considered useful only for general
      screening purposes. CONCLUSIONS: NIRS technology may be a useful tool in the
      selection of lines coming out of tomato breeding programs, allowing a quick
      estimation of mineral content. However, the estimation of soluble solids content
      and titratable acidity by NIRS must be improved.

PMID- 21953599
TI  - Direct MR arthrography of cadaveric wrists: comparison between MR imaging at 3.0T
      and 7.0T and gross pathologic inspection.
AB  - PURPOSE: To prospectively evaluate the diagnostic accuracy of magnetic resonance
      (MR) arthrography for the detection of articular cartilage abnormalities at 3.0T
      and 7.0T in cadaveric wrists. MATERIALS AND METHODS: MR imaging (MRI) was
      performed in nine cadaveric wrists (four right wrists, five left; mean age, 81.0
      +/- 9.8 years) after the intraarticular administration of gadoterate-meglumine. A
      3.0T and 7.0T MR system, mechanically identical custom-built 8-channel wrist coil
      arrays and a similar standard MRI protocol, were used. MR images were evaluated
      for visibility of articular cartilage surfaces, presence of cartilage lesions,
      and confidence of diagnosis by two independent radiologists. Open pathologic
      inspection served as reference standard. Sensitivity, specificity, negative
      predictive values (NPV) and positive predictive values (PPV), and accuracy (ACC)
      were calculated. Wilcoxon signed rank test was used to assess differences in the
      diagnostic performance. RESULTS: Visibility of articular cartilage surfaces was
      significantly better at 3.0T than at 7.0T (P < 0.001). Mean sensitivity,
      specificity, NPV, PPV, ACC for both readers were 63%, 90%, 85%, 76%, 82% at 3.0T,
      respectively, and 52%, 91%, 82%, 75%, 79% at 7.0T. The difference between 3.0T
      and 7.0T was not significant for reader 1 (P = 0.51), but was significant for
      reader 2 (P = 0.01). The level of confidence was significantly higher at 3.0T
      than at 7.0T for both readers (P = 0.004; P = 0.03). CONCLUSION: MR arthrography
      of the wrist at 7.0T is still limited by the lack of commercially available
      radiofrequency coils and limited experience in sequence optimization, resulting
      in a significantly lower visibility of anatomy, lower diagnostic accuracy, and
      level of confidence in judging cartilage lesions compared to 3.0T.

PMID- 21953600
TI  - Polymers with tailored electronic structure for high capacity lithium battery
      electrodes.

PMID- 21953601
TI  - TRPV1 antagonist, A-889425, inhibits mechanotransmission in a subclass of rat
      primary afferent neurons following peripheral inflammation.
AB  - TRPV1 (transient receptor potential vanilloid family type 1) is a nonselective
      cation channel that is activated and/or sensitized by noxious heat, protons, and
      other endogenous molecules released following tissue injury. In addition, a role
      for TRPV1 in mechanotransmission is emerging. We have recently reported that a
      selective TRPV1 receptor antagonist, A-889425, reduces mechanical allodynia and
      spinal neuron responses to mechanical stimulation of complete Freund's adjuvant
      (CFA)-inflamed rat hind paws. The population of peripheral nerve fibers through
      which TRPV1 antagonists mediate their effect on mechanotransmission have not yet
      been described. The objective of this study was to characterize TRPV1-mediated
      modulation of mechanically evoked activity in sensory axons innervating rat hind
      paws. We used an in vitro skin-nerve preparation to record neural activity from
      single axons isolated from rat tibial nerve. Single fibers were classified by
      conduction velocity, mechanical threshold, and stimulus-response relationships.
      We used A-889425 to investigate uninjured and inflamed skin afferent neuron
      populations to evoked mechanical stimulation. Application of A-889425 had no
      effect on the mechanical responsiveness of Adelta and C-fiber units innervating
      uninjured skin. In contrast, A-889425 inhibited responses of slowly conducting
      Adelta fiber units to noxious mechanical stimulation in a population of axons
      innervating CFA-inflamed hind paws. These data support a role for TRPV1 in
      mechanotransmission following peripheral inflammation, and highlight the
      importance of a distinct subclass of primary afferent neurons in mediating this
      effect.

PMID- 21953602
TI  - Acute glucocorticoid effects on the multicomponent model of working memory.
AB  - OBJECTIVE: In comparison with basal physiological levels, acute, high levels of
      cortisol affect learning and memory. Despite reports of cortisol-induced episodic
      memory effects, no study has used a comprehensive battery of tests to evaluate
      glucocorticoid effects on the multicomponent model of working memory. Here, we
      report the results of a double-blind, placebo-controlled, between-subjects study.
      METHODS: Twenty healthy young men were randomly assigned to either acute cortisol
      (30 mg hydrocortisone) or placebo administration. Participants were subjected to
      an extensive cognitive test battery that evaluated all systems of the
      multicomponent model of working memory, including various executive domains
      (shifting, updating, inhibition, planning and access to long-term memory).
      RESULTS: Compared with placebo, hydrocortisone administration increased cortisol
      blood levels and impaired working memory in storage of multimodal information in
      the episodic buffer and maintenance/reverberation of information in the
      phonological loop. Hydrocortisone also decreased performance in planning and
      inhibition tasks, the latter having been explained by changes in storage of
      information in working memory. CONCLUSIONS: Thus, hydrocortisone acutely impairs
      various components of working memory, including executive functioning. This
      effect must be considered when administering similar drugs, which are widely used
      for the treatment of many clinical disorders.

PMID- 21953603
TI  - Caffeine in Parkinson's disease: a pilot open-label, dose-escalation study.
AB  - INTRODUCTION: Epidemiologic studies consistently find an inverse association
      between caffeine use and PD. Numerous explanations exist, but are difficult to
      evaluate as caffeine's symptomatic effect and tolerability in PD are unknown.
      PATIENTS AND METHODS: We designed an open-label, 6-week dose-escalation study of
      caffeine to establish dose tolerability and evaluate potential motor/nonmotor
      benefits. Caffeine was started at 200 mg daily and was increased to a maximum of
      1,000 mg. RESULTS: Of 25 subjects, 20 tolerated 200 mg, 17 tolerated 400 mg, 7
      tolerated 800 mg, and 3 tolerated 1,000 mg. The most common adverse events were
      gastrointestinal discomfort, anxiety, and worsening/emerging tremor. At 400 mg
      daily, we found potential improvements in motor manifestations and somnolence
      (UPDRS III: -4.5 +/- 4.6, P = 0.003; Epworth: -2.0 +/- 3.0, P = 0.015).
      CONCLUSION: Maximum dose tolerability for caffeine in PD appears to be 100 to 200
      mg BID. We found pilot preliminary evidence that caffeine may improve some motor
      and nonmotor aspects of PD, which must be confirmed in longer term, placebo
      controlled, clinical trials.

PMID- 21953604
TI  - Isolation of Rhizobacteria from Jatropha curcas and characterization of produced
      ACC deaminase.
AB  - Decreased levels of ACC (1-aminocyclopropane-1-carboxylic acid) result in lower
      levels of endogenous ethylene, which eliminate the potentially inhibitory effects
      of stress-induced higher ethylene concentrations. It is worth noting the
      substantial ability of the bacterial species to colonize different environments,
      including taxonomically distinct plants cultivated in distantly separated
      geographical regions. For example, Enterobacter cloacae, designated as MSA1 and
      Enterobacter cancerogenus, designated as MSA2 were recovered from the rhizosphere
      of Jatropha in the present work. This study first time confirms the ACC deaminase
      activity in the Enterobacter cancerogenus on the preliminary basis. Several
      bacterial plant growth-promoting mechanisms were analyzed and detected like
      phosphate solubilization, siderophore production, IAA production, GA(3)
      (gibberellic acid) production and ACC deaminase activity in the isolated
      cultures. Isolates were grown until exponential growth phase to evaluate their
      ACC deaminase activity and the effect of pH, temperature, salt, metals and
      substrate concentration after the partial purification of enzyme by ion exchange
      chromatography. The FOURIER TRANSFORM INFRARED (FT-IR) spectra were recorded for
      the confirmation of alpha-ketobutyrate production. By using lineweaver Burk plot
      K(m) and V(max) value for ACC deaminase of both the organism was calculated in
      the different fractions. In this work, we discuss the possible implications of
      these bacterial mechanisms on the plant growth promotion or homeostasis
      regulation in natural conditions.

PMID- 21953605
TI  - Reduced risk of breast, endometrial and ovarian cancer in women with celiac
      disease.
AB  - Women with celiac disease (CD) may be at decreased risk of female hormone-related
      cancers given the observed reduction in breast cancer seen in some cohorts. Using
      biopsy data from all 28 pathology departments in Sweden, we identified 17,852
      women with CD who were diagnosed between 1969 and 2007. We used Cox regression
      model to estimate their risk of breast, endometrial and ovarian cancer and then
      compared them with 88,400 age- and sex-matched controls. The results indicate
      that individuals with CD were at a lower risk for all three outcomes: breast
      cancer (hazard ratio, HR = 0.85; 95% CI = 0.72-1.01), endometrial cancer (HR =
      0.60; 95% CI =0.41-0.86) and ovarian cancer (HR = 0.89; 95% CI =0.59-1.34). This
      inverse relationship was strengthened when we excluded the first year of follow
      up beyond CD diagnosis (breast: HR = 0.82; 95% CI =0.68-0.99; endometrial: HR =
      0.58; 0.39-0.87; ovarian cancer: HR = 0.72; 0.45-1.15). In conclusion, CD seems
      to be inversely related not only to breast cancer but also to endometrial and
      ovarian cancer. Potential explanations include shared risk factors and early
      menopause.

PMID- 21953606
TI  - Peak and decline in cancer incidence, mortality, and prevalence at old ages.
AB  - BACKGROUND: Cancer incidence and mortality increase with age through much of
      adulthood, but earlier work has found that these rates decline among the very
      elderly. To compare incidence and mortality at the oldest ages, the authors
      investigated both in the same large population, which comprised 9.5% of the
      United States in 2000. The authors also report age-specific prevalence among the
      elderly, which has received little attention. METHODS: Twenty-three cancer types
      were studied in men, and 24 cancer types were studied in women. Patient records
      were obtained from the SEER 9 cancer registries, and population figures were
      taken from the 2000 US Census. The authors explored the reliability of census
      data on the oldest old, which has been questioned. RESULTS: Age-specific
      incidence, prevalence, and mortality results are presented for the years 1998 to
      2002. Incidence and mortality usually decreased or plateaued at very old ages.
      Prevalence usually decreased swiftly at ages >90 years. When there was
      statistical power, incidence normally peaked between ages 75 years and 90 years,
      dropping abruptly afterward. With several large exceptions, peak incidence and
      mortality coincided within +/-5 years. Both rates often trended toward zero among
      centenarians, who may be asymptomatic or insusceptible. CONCLUSIONS: The current
      results were found to be consistent with autopsy and survival studies. Most age
      specific models of carcinogenesis are based on cancer rate data for ages <85
      years. The authors argue that these models could not fit the current results
      without fundamental modification and outline biologic mechanisms for such
      modification, mostly cellular and tissue senescence. They also recommend caution
      to researchers who use census data on the very elderly.

PMID- 21953607
TI  - Interferon signals and monocytic sensitization of the interferon-gamma signaling
      pathway in the peripheral blood of patients with rheumatoid arthritis.
AB  - OBJECTIVE: Both type I interferons (IFNalpha and IFNbeta) and type II IFN
      (IFNgamma) signal via pSTAT-1. Immunohistochemistry and the gene expression
      signatures of rheumatoid arthritis (RA) synovial tissue suggest an activated
      IFN/STAT-1 signaling pathway. The aim of this study was to determine the systemic
      activity of the IFN/STAT-1 signaling pathway in the peripheral blood cells of
      patients with RA. METHODS: Fluorocytometry or quantitative polymerase chain
      reaction was used to measure the expression of STAT-1, pSTAT-1, and IFN-inducible
      genes (monokine induced by interferon-gamma [MIG], interferon-gamma-inducible
      protein 10 [IP-10], and 2',5'-oligoadenylate synthetase [OAS]) in the peripheral
      blood mononuclear cells (PBMCs) and purified CD14+ peripheral blood monocytes of
      patients with RA and healthy control subjects. PBMCs were also incubated for 48
      hours with IFNs and several other cytokines to investigate influences on STAT-1
      levels. To examine the significance of STAT-1 activation in RA monocytes after
      stimulation with IFNgamma, the expression of pSTAT-1 and of the IFNgamma
      inducible chemokine MIG was measured using fluorocytometry. RESULTS: Levels of
      STAT-1 were significantly increased in peripheral lymphocytes and monocytes from
      patients with RA compared with those from healthy control subjects. STAT-1 levels
      correlated well with RA disease activity, as measured by the Disease Activity
      Score in 28 joints and the Clinical Disease Activity Index. Furthermore, STAT-1
      messenger RNA expression in RA CD14+ monocytes correlated with the expression of
      other IFN-target genes, such as IP-10, OAS, or MIG. In RA PBMCs, STAT-1
      expression was increased not only by IFNs but also by tumor necrosis factor. RA
      monocytes demonstrated a considerably higher increase in pSTAT-1 and MIG levels
      upon IFNgamma stimulation when compared with monocytes from control subjects,
      indicating that RA monocytes are more sensitive to IFNgamma stimulation.
      CONCLUSION: In addition to supporting the role of IFNs in systemic
      proinflammatory activity, the results of this study further suggest preactivation
      of the IFNgamma/STAT-1 signaling pathway, especially in RA monocytes.

PMID- 21953608
TI  - Alkyne-aldehyde reductive C-C coupling through ruthenium-catalyzed transfer
      hydrogenation: direct regio- and stereoselective carbonyl vinylation to form
      trisubstituted allylic alcohols in the absence of premetallated reagents.
AB  - Nonsymmetric 1,2-disubstituted alkynes engage in reductive coupling to a variety
      of aldehydes under the conditions of ruthenium-catalyzed transfer hydrogenation
      by employing formic acid as the terminal reductant and delivering the products of
      carbonyl vinylation with good to excellent levels of regioselectivity and with
      complete control of olefin stereochemistry. As revealed in an assessment of the
      ruthenium counterion, iodide plays an essential role in directing the
      regioselectivity of C-C bond formation. Isotopic labeling studies corroborate
      reversible catalytic propargyl C-H oxidative addition in advance of the C-C
      coupling, and demonstrate that the C-C coupling products do not experience
      reversible dehydrogenation by way of enone intermediates. This transfer
      hydrogenation protocol enables carbonyl vinylation in the absence of
      stoichiometric metallic reagents.

PMID- 21953610
TI  - Neuroprotection by hypoxic preconditioning involves upregulation of hypoxia
      inducible factor-1 in a prenatal model of acute hypoxia.
AB  - The molecular pathways underlying the neuroprotective effects of preconditioning
      are promising, potentially drugable targets to promote cell survival. However,
      these pathways are complex and are not yet fully understood. In this study we
      have established a paradigm of hypoxic preconditioning based on a chick embryo
      model of normobaric acute hypoxia previously developed by our group. With this
      model, we analyzed the role of hypoxia-inducible factor-1alpha (HIF-1alpha)
      stabilization during preconditioning in HIF-1 signaling after the hypoxic injury
      and in the development of a neuroprotective effect against the insult. To this
      end, we used a pharmacological approach, based on the in vivo administration of
      positive (Fe(2+), ascorbate) and negative (CoCl(2)) modulators of the activity of
      HIF-prolyl hydroxylases (PHDs), the main regulators of HIF-1. We have found that
      preconditioning has a reinforcing effect on HIF-1 accumulation during the
      subsequent hypoxic injury. In addition, we have also demonstrated that HIF-1
      induction during hypoxic preconditioning is necessary to obtain an enhancement in
      HIF-1 accumulation and to develop a tolerance against a subsequent hypoxic
      injury. We provide in vivo evidence that administration of Fe(2+) and ascorbate
      modulates HIF accumulation, suggesting that PHDs might be targets for
      neuroprotection in the CNS.

PMID- 21953609
TI  - Hormonal and physical markers of puberty and their relationship to adolescent
      typical novelty-directed behavior.
AB  - The extent to which characteristic adolescent behaviors are associated with
      pubertal changes or driven by more general, puberty-independent developmental
      alterations is largely unknown. Using physiological and hormonal markers of
      puberty, this experiment characterized pubertal timing across adolescence and
      examined the relationships among these variables and novelty-directed behaviors.
      Males and females were tested for response to novelty at P28, P32, P36, P40, P44,
      P48, and P75, and examined for balano-preputial skinfold separation and sperm
      presence (males) or vaginal opening (females), followed by blood collection for
      hormonal assessments. Despite earlier pubertal maturation in females, with
      maturation generally completed by P36 in females and P44 in males, novelty
      directed behavior peaked at P32 and P36 in both sexes, and was unrelated to
      pubertal measures. These data support the suggestion that the ontogenetic peak in
      this behavior during adolescence is not notably puberty dependent.

PMID- 21953611
TI  - Prospectively determined impact of type 1 diabetes on brain volume during
      development.
AB  - OBJECTIVE: The impact of type 1 diabetes mellitus (T1DM) on the developing
      central nervous system is not well understood. Cross-sectional, retrospective
      studies suggest that exposure to glycemic extremes during development is harmful
      to brain structure in youth with T1DM. However, these studies cannot identify
      brain regions that change differentially over time depending on the degree of
      exposure to glycemic extremes. RESEARCH DESIGN AND METHODS: We performed a
      longitudinal, prospective structural neuroimaging study of youth with T1DM (n =
      75; mean age = 12.5 years) and their nondiabetic siblings (n = 25; mean age =
      12.5 years). Each participant was scanned twice, separated by 2 years. Blood
      glucose control measurements (HbA(1c), glucose meter results, and reports of
      severe hypoglycemia) were acquired during the 2-year follow-up. Sophisticated
      image registration algorithms were performed, followed by whole brain and voxel
      wise statistical analyses of the change in gray and white matter volume,
      controlling for age, sex, and age of diabetes onset. RESULTS: The T1DM and
      nondiabetic control (NDC) sibling groups did not differ in whole brain or voxel
      wise change over the 2-year follow-up. However, within the T1DM group,
      participants with more hyperglycemia had a greater decrease in whole brain gray
      matter compared with those with less hyperglycemia (P < 0.05). Participants who
      experienced severe hypoglycemia had greater decreases in occipital/parietal white
      matter volume compared with those with no severe hypoglycemia (P < 0.05) and
      compared with the NDC sibling group (P < 0.05). CONCLUSIONS: These results
      demonstrate that within diabetes, exposure to hyperglycemia and severe
      hypoglycemia may result in subtle deviation from normal developmental
      trajectories of the brain.

PMID- 21953612
TI  - Specific control of pancreatic endocrine beta- and delta-cell mass by class IIa
      histone deacetylases HDAC4, HDAC5, and HDAC9.
AB  - OBJECTIVE: Class IIa histone deacetylases (HDACs) belong to a large family of
      enzymes involved in protein deacetylation and play a role in regulating gene
      expression and cell differentiation. Previously, we showed that HDAC inhibitors
      modify the timing and determination of pancreatic cell fate. The aim of this
      study was to determine the role of class IIa HDACs in pancreas development.
      RESEARCH DESIGN AND METHODS: We took a genetic approach and analyzed the
      pancreatic phenotype of mice lacking HDAC4, -5, and -9. We also developed a novel
      method of lentiviral infection of pancreatic explants and performed gain-of
      function experiments. RESULTS: We show that class IIa HDAC4, -5, and -9 have an
      unexpected restricted expression in the endocrine beta- and delta-cells of the
      pancreas. Analyses of the pancreas of class IIa HDAC mutant mice revealed an
      increased pool of insulin-producing beta-cells in Hdac5(-/-) and Hdac9(-/-) mice
      and an increased pool of somatostatin-producing delta-cells in Hdac4(-/-) and
      Hdac5(-/-) mice. Conversely, HDAC4 and HDAC5 overexpression showed a decreased
      pool of insulin-producing beta-cells and somatostatin-producing delta-cells.
      Finally, treatment of pancreatic explants with the selective class IIa HDAC
      inhibitor MC1568 enhances expression of Pax4, a key factor required for proper
      beta-and delta-cell differentiation and amplifies endocrine beta- and delta
      cells. CONCLUSIONS: We conclude that HDAC4, -5, and -9 are key regulators to
      control the pancreatic beta/delta-cell lineage. These results highlight the
      epigenetic mechanisms underlying the regulation of endocrine cell development and
      suggest new strategies for beta-cell differentiation-based therapies.

PMID- 21953613
TI  - Induction of heme oxygenase 1 prevents progression of liver fibrosis in Mdr2
      knockout mice.
AB  - Induction or overexpression of the heme-degrading enzyme, heme oxygenase 1 (HO
      1), has been shown to protect mice from liver damage induced by acute
      inflammation. We have investigated the effects of HO-1 induction in a mouse model
      of chronic liver inflammation and fibrogenesis with progression to hepatocellular
      carcinoma (HCC) (Mdr2ko; FVB.129P2-Abcb4(tm1Bor)). HO-1 was induced in vivo by
      treatment with cobalt protoporphyrin IX, starting at week 5 or 12 of mice
      lifespan, and continued for 7 weeks. Our results showed that HO-1 induction
      reduced liver damage and chronic inflammation by regulating immune cell
      infiltration or proliferation as well as tumor necrosis factor receptor
      signaling. Fibrosis progression was significantly reduced by HO-1 induction in
      mice with mild, as well as established, portal and lobular fibrosis. HO-1
      induction significantly suppressed hepatic stellate cell activation. During
      established fibrosis, HO-1 induction was able to revert portal inflammation and
      fibrosis below levels observed at the start of treatment. Moreover,
      hepatocellular proliferation and signs of dysplasia were decreased after HO-1
      induction. CONCLUSION: Induction of HO-1 interferes with chronic inflammation and
      fibrogenesis and, in consequence, might delay progression to HCC.

PMID- 21953614
TI  - Usefulness of anti-p155 autoantibody for diagnosing cancer-associated
      dermatomyositis: a systematic review and meta-analysis.
AB  - OBJECTIVE: Anti-p155 autoantibody, which was recently described in adult patients
      with dermatomyositis (DM), seems to be associated with cancer in this population.
      We performed a systematic review and meta-analysis to ascertain the accuracy of
      anti-p155 testing for the diagnosis of cancer-associated myositis. METHODS: We
      searched relevant databases, with no restrictions on study design or language,
      for original studies that included adult patients with probable/definite DM or
      amyopathic DM who were evaluated for neoplasm and anti-p155 status. Pooled
      sensitivity and specificity were calculated using a bivariate model. We computed
      the diagnostic odds ratio (OR), likelihood ratios (LRs) for positive and negative
      test results, positive and negative predictive values, and the summary receiver
      operating characteristic (SROC) curve. Statistical heterogeneity between studies
      was assessed using the I(2)  statistic, and 95% confidence intervals (95% CIs)
      were computed for the parameters studied. RESULTS: Six studies including a total
      of 312 adult patients with DM were selected. The pooled sensitivity of anti-p155
      for diagnosing cancer-associated DM was 78% (95% CI 45-94%), and specificity was
      89% (95% CI 82-93%). The diagnostic OR was 27.26 (95% CI 6.59-112.82), and LRs
      for positive and negative test results were 6.79 (95% CI 4.11-11.23) and 0.25
      (95% CI 0.08-0.76), respectively. Heterogeneity was substantial except with
      regard to the LR for a positive test result. The area under the SROC curve was
      0.91 (95% CI 0.88-0.93). Taking the pooled prevalence of 17% as pretest
      probability, anti-p155 had a positive predictive value of 58% and a negative
      predictive value of 95%. CONCLUSION: Our findings indicate that anti-p155
      autoantibody determination is useful for diagnosing cancer-associated myositis
      and guiding disease management.

PMID- 21953615
TI  - Mouse versus rat: Profound differences in meiotic regulation at the level of the
      isolated oocyte.
AB  - Cumulus cell-enclosed oocytes (CEO), denuded oocytes (DO), or dissected follicles
      were obtained 44-48 hr after priming immature mice (20-23 days old) with 5 IU or
      immature rats (25-27 days old) with 12.5 IU of equine chorionic gonadotropin, and
      exposed to a variety of culture conditions. Mouse oocytes were more effectively
      maintained in meiotic arrest by hypoxanthine, dbcAMP, IBMX, milrinone, and 8-Br
      cGMP. Atrial natriuretic peptide, a guanylate cyclase activator, suppressed
      maturation in CEO from both species, but mycophenolic acid reversed IBMX
      maintained meiotic arrest in mouse CEO with little activity in rat CEO. IBMX
      arrested mouse, but not rat, CEO were induced to undergo germinal vesicle
      breakdown (GVB) by follicle-stimulating hormone (FSH) and amphiregulin, while
      human chorionic gonadotropin (hCG) was ineffective in both species. Nevertheless,
      FSH and amphiregulin stimulated cumulus expansion in both species. FSH and hCG
      were both effective inducers of GVB in cultured mouse and rat follicles while
      amphiregulin was stimulatory only in mouse follicles. Changing the culture medium
      or altering macromolecular supplementation had no effect on FSH-induced
      maturation in rat CEO. The AMP-activated protein kinase (AMPK) activator, AICAR,
      was a potent stimulator of maturation in mouse CEO and DO, but only marginally
      stimulatory in rat CEO and ineffective in rat DO. The AMPK inhibitor, compound C,
      blocked meiotic induction more effectively in hCG-treated mouse follicles and
      heat-treated mouse CEO. Both agents produced contrasting results on polar body
      formation in cultured CEO in the two species. Active AMPK was detected in
      germinal vesicles of immature mouse, but not rat, oocytes prior to hCG-induced
      maturation in vivo; it colocalized with chromatin after GVB in rat and mouse
      oocytes, but did not appear at the spindle poles in rat oocytes as it did in
      mouse oocytes. Finally, cultured mouse and rat CEO displayed disparate maturation
      responses to energy substrate manipulation. These data highlight significant
      differences in meiotic regulation between the two species, and demonstrate a
      greater potential in mice for control at the level of the cumulus CEO.

PMID- 21953616
TI  - A phase and frequency alignment protocol for 1H MRSI data of the prostate.
AB  - (1)H MRSI of the prostate reveals relative metabolite levels that vary according
      to the presence or absence of tumour, providing a sensitive method for the
      identification of patients with cancer. Current interpretations of prostate data
      rely on quantification algorithms that fit model metabolite resonances to
      individual voxel spectra and calculate relative levels of metabolites, such as
      choline, creatine, citrate and polyamines. Statistical pattern recognition
      techniques can potentially improve the detection of prostate cancer, but these
      analyses are hampered by artefacts and sources of noise in the data, such as
      variations in phase and frequency of resonances. Phase and frequency variations
      may arise as a result of spatial field gradients or local physiological
      conditions affecting the frequency of resonances, in particular those of citrate.
      Thus, there are unique challenges in developing a peak alignment algorithm for
      these data. We have developed a frequency and phase correction algorithm for
      automatic alignment of the resonances in prostate MRSI spectra. We demonstrate,
      with a simulated dataset, that alignment can be achieved to a phase standard
      deviation of 0.095  rad and a frequency standard deviation of 0.68  Hz for the
      citrate resonances. Three parameters were used to assess the improvement in peak
      alignment in the MRSI data of five patients: the percentage of variance in all
      MRSI spectra explained by their first principal component; the signal-to-noise
      ratio of a spectrum formed by taking the median value of the entire set at each
      spectral point; and the mean cross-correlation between all pairs of spectra.
      These parameters showed a greater similarity between spectra in all five datasets
      and the simulated data, demonstrating improved alignment for phase and frequency
      in these spectra. This peak alignment program is expected to improve pattern
      recognition significantly, enabling accurate detection and localisation of
      prostate cancer with MRSI.

PMID- 21953617
TI  - The coexistence of chronic lymphocytic leukemia and myeloproliperative neoplasms:
      a retrospective multicentric GIMEMA experience.
AB  - Although the coexistence of chronic lymphocytic leukemia (CLL) and
      myeloproliferative neoplasms (MPN) has been sporadically reported in the
      literature, no systematic studies on this disease association are available. We
      retrospectively analyzed 46 patients affected by CLL/MPN referred by 15 Italian
      GIMEMA centers. The aim of this retrospective multicenter study was to define the
      following: clinico-biological characteristics, possible familiarity, clinical
      course of both diseases, and influence of MPN chemotherapy on the course of CLL.
      Among 46 patients, 30 patients were males, 16 patients were females; median age
      was 71 years. Only one case had familiar CLL. Myeloproliferative disorders
      consisted of essential thrombocytemia in 18 cases, polycythemia vera in 10 cases,
      chronic myeloid leukemia in 9 cases, primary myelofibrosis in 6 cases, and
      MPN/myelodysplastic syndrome in 3 cases. The lymphoproliferative disorder was
      diagnosed as monoclonal B-cell lymphocytosis in 8 patients and as Binet Stage A
      CLL in 38 patients. After a median follow-up of 49 months, 9 patients experienced
      progressive CLL and only 6 patients required treatment after a median of 57.5
      months. The biological profile confirmed a subset of low-risk CLL. Twenty
      patients received chemotherapy for MPN without influence on the course of CLL:
      lymphocyte counts remained unchanged after 3, 6, and 12 months of treatment. This
      series is the largest so far reported in literature. The diagnosis of concomitant
      CLL/MPN is a rare event and lymphoproliferative disorders present a clinical
      indolent course with a low-risk biological profile. MPN therapy does not
      interfere with the prognosis of patients with CLL.

PMID- 21953619
TI  - Segregation of visual inputs from different regions of the compound eye in two
      parallel pathways through the anterior optic tubercle of the bumblebee (Bombus
      ignitus).
AB  - Visually guided behaviors require the brain to extract features of the visual
      world and to integrate them in a context-specific manner. Hymenopteran insects
      have been prime models for ethological research into visual behaviors for decades
      but knowledge about the underlying central processing is very limited. This is
      particularly the case for sky-compass navigation. To learn more about central
      processing of visual information in general and specifically to reveal a possible
      polarization vision pathway in the bee brain, we used tracer injections to
      investigate the pathways through the anterior optic tubercle, a prominent output
      target of the insect optic lobe, in the bumblebee Bombus ignitus. The anterior
      optic tubercle of the bumblebee is a small neuropil of 200 MUm width and is
      located dorsolateral to the antennal lobe at the anterior surface of the brain.
      It is divided into a larger upper and a smaller lower subunit, both of which
      receive input from the optic lobe and connect to the lateral accessory lobe, and
      the contralateral tubercle, via two parallel pathways. The lower subunit receives
      input from the dorsal rim area (DRA) of the compound eye. The bumblebee DRA
      shares structural similarities with polarization-sensitive DRAs of other insects
      and looks similar to that of honeybees. We identified several neurons within this
      pathway that could be homologous to identified polarization-sensitive neurons in
      the locust brain. We therefore conclude that the pathway through the lower
      subunit of the anterior optic tubercle could carry polarization information from
      the periphery to the central brain.

PMID- 21953618
TI  - Hepatocyte growth factor-regulated tyrosine kinase substrate (Hgs) is involved in
      BMP signaling through phosphorylation of SMADS and TAK1 in early mouse embryo.
AB  - Hepatocyte growth factor-regulated tyrosine kinase substrate that is encoded by
      Hgs promotes degradation of ubiquitinated signaling molecule in the early
      endosome. We previously reported that a targeted mutation in Hgs results in
      embryonic lethality soon after gastrulation in the mouse. Here, we report that
      downstream target genes for BMP signaling were highly down-regulated in the Hgs
      mutant embryos. We also showed that Hgs is required for phosphorylation of
      SMAD1/5/8 and TAK1/p38 to transduce BMP signaling. Furthermore, we found that HGS
      functions to localize TAK1 in early endosome for its activation. These results
      suggest that HGS is critical to localize TAK1 to early endosome for transducing
      BMP signaling for proper development. Our data revealed a new mechanism to modify
      BMP signaling by Hgs during early mouse development.

PMID- 21953620
TI  - Detection of a minor amorphous phase in crystalline etoricoxib by dynamic
      mechanical analysis: comparison with Raman spectroscopy and modulated
      differential scanning calorimetry.
AB  - Detection and quantification of the amorphous phase of etoricoxib bulk drug
      substances, a selective cycloogenase-2 inhibitor used for the treatment of
      osteoarthritis, rheumatoid arthritis, and dental pain, was carried out using
      modulated differential scanning calorimetry (MDSC), dynamic mechanical analysis
      (DMA), and Raman spectroscopy. Detection of amorphous content in pharmaceutical
      powders by DMA is a special application of dynamic mechanical spectroscopy. DMA
      was found to be a sensitive technique, able to detect the presence of an
      amorphous phase in a crystalline phase at concentrations as low as 0.5%. The
      limit of detection (LOD) determined for DMA was 2.5%. In comparison, Raman
      spectroscopy and MDSC had LOD values of 2% and 5% amorphous, respectively.

PMID- 21953621
TI  - Electrophysiological testing of spinal accessory nerve in suspected cases of
      nerve transection.
AB  - INTRODUCTION: In this study we sought to determine whether standard
      electrophysiological testing of the spinal accessory nerve (SAN) accurately
      identifies patients who would benefit from surgical repair. METHODS: Sixteen
      consecutive patients sent for surgical evaluation of unilateral SAN injury were
      studied clinically and electrophysiologically. RESULTS: All patients demonstrated
      a low-amplitude SAN compound muscle action potential (CMAP) that required a
      higher stimulus intensity to obtain it than on the unaffected side. Upper
      trapezius needle electromyography showed dense fibrillation potentials in 16 of
      16 nerves, with voluntary motor unit potentials (MUPs) in 5 of 16.
      Intraoperatively, 12 of 16 nerves were transected; 4 of 16 had neuromas across
      which there was no nerve action potential. Patients underwent direct repair (6 of
      16) or interpositional nerve grafting (10 of 16). Fourteen of 15 patients seen
      postoperatively had improvement in pain, muscle bulk, and range of motion.
      CONCLUSIONS: Surgical exploration of the SAN is warranted in patients with
      clinical signs of severe injury, even when electrophysiological testing shows low
      amplitude CMAPs and/or residual MUPs.

PMID- 21953622
TI  - Lipase-catalysed production of triacylglycerols enriched in pinolenic acid at the
      sn-2 position from pine nut oil.
AB  - BACKGROUND: The purpose of this study was to produce triacylglycerols (TAGs)
      enriched in pinolenic acid (PLA) at the sn-2 position using the principle of acyl
      migration, from the pine nut oil containing PLA esterified exclusively at the sn
      3 position. RESULTS: Two types of lipase-catalysed reactions, i.e. redistribution
      and reesterification of fatty acids, were successively performed using seven
      commercially available lipases as biocatalysts. Of the lipases tested, Novozym
      435 and Lipozyme TL IM were effective biocatalysts for positioning PLA at the sn
      2 location. These biocatalysts were selected for further evaluation of the
      effects of reaction parameters, such as temperature and water content on the
      migration of PLA residues to the sn-2 position and TAG content. For both lipases,
      a significant decrease in TAG content was observed after the lipase-catalysed
      redistribution of fatty acids for both lipases. The reduced TAG content could be
      enhanced up to approx. 92%, through lipase-catalysed re-esterification of the
      hydrolysed fatty acids under vacuum. CONCLUSION: TAG enriched in PLA at the sn-2
      position was synthesised from pine nut oil via lipase-catalysed redistribution
      and re-esterification of fatty acid residues using Lipozyme TL IM and Novozym 435
      as biocatalysts.

PMID- 21953623
TI  - Granulocyte colony stimulating factor neuroprotective effects on spinal
      motoneurons after ventral root avulsion.
AB  - G-CSF is a glycoprotein commonly used to treat neutropenia. Recent studies have
      shown that the G-CSF receptor (G-CSF-R) is expressed by neurons in the central
      nervous system (CNS), and neuroprotective effects of G-CSF have been observed. In
      this study, the influence of G-CSF treatment on the glial reactivity and synaptic
      plasticity of spinal motoneurons in rats subjected to ventral root avulsion (VRA)
      was investigated. Lewis rats (7 weeks old) were subjected to unilateral VRA and
      divided into two groups: G-CSF and placebo treated. The drug treated animals were
      injected subcutaneously with 200 MUg/kg/day of G-CSF for 5 days post lesion. The
      placebo group received saline buffer. After 2 weeks, both groups were sacrificed
      and their lumbar intumescences processed for transmission electron microscopy
      (TEM), motoneuron counting, and immunohistochemistry with antibodies against
      GFAP, Iba-1, and synaptophysin. Furthermore, in vitro analysis was carried out,
      using newborn cortical derived astrocytes. The results indicated increased
      neuronal survival in the G-CSF treated group coupled with synaptic preservation.
      TEM analyses revealed an improved preservation of the synaptic covering in
      treated animals. Additionally, the drug treated group showed an increase in
      astroglial reactivity both in vivo and in vitro. The astrocytes also presented an
      increased cell proliferation rate when compared with the controls after 3 days of
      culturing. In conclusion, the present results suggest that G-CSF has an influence
      on the stability of presynaptic terminals in the spinal cord as well as on the
      astroglial reaction, indicating a possible neuroprotective action.

PMID- 21953624
TI  - LC-ESI-MS/MS determination of paclitaxel on dried blood spots.
AB  - A simple and rapid high-performance liquid chromatography-tandem mass
      spectrometric assay for determination of paclitaxel on rat dried blood spots was
      developed and validated. The extracted sample was chromatographed without further
      treatment using a reverse-phase Oyster ODS3, 4.6 * 50 mm, 3 um column with mass
      spectrometry detection. The mobile phase comprised of acetonitrile-water, 60:40
      v/v, with a flow rate of 0.4 mL/min was used. The calibration was linear over the
      range 0.2-20 ng/mL. The limits of detection and quantification were 0.08 and 0.2
      ng/mL, respectively. The intra- and inter-day precision (CV%) and accuracy
      (relative error %) were less than 10 and 12%, respectively.

PMID- 21953625
TI  - Folate, vitamin B(6) , vitamin B(12) , methionine and alcohol intake in relation
      to ovarian cancer risk.
AB  - Folate, methionine, vitamin B(6)  and vitamin B(12)  may influence carcinogenesis
      due to their roles in the one-carbon metabolism pathway, which is critical for
      DNA synthesis, methylation and repair. Low intake of these nutrients has been
      associated with an increased risk of breast, colon and endometrial cancers.
      Previous studies that have examined the relation between these nutrients and
      ovarian cancer risk have been inconsistent and have had limited power to examine
      the relation by histologic subtype. We investigated the association between
      folate, methionine, vitamin B(6) , vitamin B(12)  and alcohol among 1910 women
      with ovarian cancer and 1989 controls from a case-control study conducted in
      eastern Massachusetts and New Hampshire from 1992 to 2008. Diet was assessed via
      food frequency questionnaire. Participants were asked to recall diet one-year
      before diagnosis or interview. Logistic regression models were used to calculate
      odds ratios (OR) and 95% confidence intervals (95% CIs). We also examined whether
      the associations varied by ovarian cancer histologies using polytomous logistic
      regression. We observed an inverse association between dietary vitamin B(6) 
      (covariate-adjusted OR = 0.76, 95% CI 0.64-0.92; p(trend)  = 0.002) and
      methionine intake (covariate-adjusted OR = 0.72, 95% CI = 0.60-0.87; p(trend)  <
      0.001) and ovarian cancer risk comparing the highest to lowest quartile. The
      association with dietary vitamin B(6)  was strongest for serous borderline
      (covariate-adjusted OR = 0.49, 95% CI = 0.32-0.77; p(trend)  = 0.001) and serous
      invasive (covariate-adjusted OR = 0.74, 95% CI = 0.58-0.94; p(trend)  = 0.012)
      subtypes. Overall, we observed no significant association between folate and
      ovarian cancer risk. One-carbon metabolism related nutrients, especially vitamin
      B(6)  and methionine, may lower ovarian cancer risk.

PMID- 21953626
TI  - Growth of single crystal graphene arrays by locally controlling nucleation on
      polycrystalline Cu using chemical vapor deposition.

PMID- 21953628
TI  - Effects of pelvic organ prolapse repair on urinary symptoms: a comparative study
      between the laparoscopic and vaginal approach.
AB  - OBJECTIVE: To compare changes in urinary symptoms before and after pelvic organ
      prolapse (POP) surgery, using either laparoscopic sacrocolpopexy (LSC) or
      transvaginal porcine dermis hammock placement with sacrospinous ligament
      suspension (VS). MATERIALS AND METHODS: Data were prospectively collected from
      all women undergoing POP surgery between May 2001 and October 2009. Pre- and
      postoperative urinary symptoms, Urinary Distress Inventory (UDI), and Urinary
      Impact Questionnaires (UIQ) scores were compared within and between groups. A
      generalized linear model was used for multivariate analysis. RESULTS: Out of the
      151 patients included, 87 patients underwent LSC, and 64 VS. Overall, after a
      median follow-up of 32.4 months, POP surgery improved urinary frequency (P =
      0.006), voiding difficulty (P = 0.001), stress urinary incontinence (SUI) (P =
      0.001), but not urgency (P = 0.29). VS was more effective in treating SUI (P <
      0.001 vs. 0.52) while LSC more effective on voiding difficulty (P = 0.01 vs.
      0.08). Postoperative de novo symptoms were observed in 35.8% of patients with no
      difference between the groups (P = 0.06). UDI (P = 0.04) and UIQ (P = 0.01)
      scores were significantly lower after surgery. However, LSC significantly
      improved UDI (P = 0.03) with no effect on UIQ (P = 0.29) scores while VS
      significantly improved both scores (P = 0.02 and 0.001, respectively). Upon
      multivariate analysis, only the improvement in the impact of urinary symptoms on
      daily living was independently associated to VS (OR = 5.45 [95% confidence
      interval 2.20-13.44], P = 0.01). CONCLUSION: Most preoperative urinary symptoms
      decreased after POP surgery with equivalent proportion of de novo symptoms after
      vaginal and laparoscopic approaches.

PMID- 21953627
TI  - Accelerated aortic imaging using small field of view imaging and
      electrocardiogram-triggered quadruple inversion recovery magnetization
      preparation.
AB  - PURPOSE: To accelerate and optimize black blood properties of the quadruple
      inversion recovery (QIR) technique for imaging the abdominal aortic wall.
      MATERIALS AND METHODS: QIR inversion delays were optimized for different heart
      rates in simulations and phantom studies by minimizing the steady state
      magnetization of blood for T(1) = 100-1400 ms. To accelerate and improve black
      blood properties of aortic vessel wall imaging, the QIR prepulse was combined
      with zoom imaging and (a) "traditional" and (b) "trailing" electrocardiogram
      (ECG) triggering. Ten volunteers were imaged pre- and post-contrast
      administration using a conventional ECG-triggered double inversion recovery (DIR)
      and the two QIR implementations in combination with a zoom-TSE readout. RESULTS:
      The QIR implemented with "trailing" ECG-triggering resulted in consistently good
      blood suppression as the second inversion delay was timed during maximum systolic
      flow in the aorta. The blood signal-to-noise ratio and vessel wall to blood
      contrast-to-noise ratio, vessel wall sharpness, and image quality scores showed a
      statistically significant improvement compared with the traditional QIR
      implementation with and without ECG-triggering. CONCLUSION: We demonstrate that
      aortic vessel wall imaging can be accelerated with zoom imaging and that
      "trailing" ECG-triggering improves black blood properties of the aorta which is
      subject to motion and variable blood flow during the cardiac cycle.

PMID- 21953630
TI  - Predictive clinical outcome of the intratumoral CD66b-positive neutrophil-to-CD8
      positive T-cell ratio in patients with resectable nonsmall cell lung cancer.
AB  - BACKGROUND: The role of the interaction between tumor cells and inflammatory
      cells in nonsmall cell lung carcinoma (NSCLC) is unclear. In this study, the
      authors assessed the prognostic impact of intratumoral cluster of differentiation
      66b (carcinoembryonic antigen-related cell adhesion molecule 8 [CD66b])-positive
      neutrophils and of the intratumoral CD66b-positive neutrophil-to-cluster of
      differentiation 8 (cell surface antigen T8 [CD8])-positive lymphocytes (the CD66b
      positive neutrophil-to-CD8-positive lymphocyte ratio [iNTR]) in patients with
      resectable NSCLC. METHODS: Expression levels of CD66b and CD8 were evaluated by
      immunohistochemistry on tissue microarrays consisting of 632 NSCLC specimens from
      patients who underwent curative surgery. The relation between clinicopathologic
      variables and patient outcome was assessed. RESULTS: Intratumoral CD66b-positive
      neutrophils were elevated in 318 patients (50%). In univariate analysis, an
      increase in CD66b-positive cells was associated with a high cumulative incidence
      of relapse (CIR) (median CIR, 51 months for low CD66b-positive cell density; 36
      months for high CD66b-positive cell density; P = .002) and trended toward worse
      overall survival (OS) (median OS, 57 months for low CD66b-positive cell density;
      54 months for high CD66b-positive cell density; P = .088). The iNTR was elevated
      in 190 patients (30%). An increased iNTR was strongly associated with both a high
      CIR (median CIR: 43 months for an iNTR <=1; 34 months for an iNTR >1; P < .0001)
      and poor OS (median OS: 60 months for an iNTR <=1; 46 months for an iNTR >1; P <
      .0001). In multivariate analysis, independent prognostic factors for a higher CIR
      were high iNTR (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.56-0.90;
      P = .005) and tumor stage >I, (HR, 0.39; 95% CI, 0.30-0.52; P < .0001).
      Independent prognostic factors for worse OS were a high iNTR (HR, 0.70; 95% CI,
      0.54-0.91; P = .007) and tumor stage >I (HR, 0.35; 95% CI, 0.26-0.47; P < .0001).
      CONCLUSIONS: The current results indicated that the iNTR is a novel, independent
      prognostic factor for a high rate of disease recurrence and poor OS in patients
      with resectable NSCLC.

PMID- 21953629
TI  - Levetiracetam in primary orthostatic tremor: a double-blind placebo-controlled
      crossover study.
AB  - BACKGROUND: In a double-blind crossover study we evaluated the antitremor effect
      of a 4-week treatment with either escalating dosages of levetiracetam or placebo
      in orthostatic tremor. METHODS: Twelve patients with orthostatic tremor
      participated in the study. Primary end point was improvement in stance duration.
      Secondary end points were total track length of the sway path and tremor total
      power. The patients' impression of impairment was assessed by a visual analog
      scale and quality of life by the SF-36. RESULTS: We found no significant effect
      of dosage or treatment on stance duration (P = .175), total track length (P =
      .690), total power (P = .280), or visual analog scale (P =.735). Neither was SF
      36 differentially changed by levetiracetam or placebo (SF-36, Physical Component
      Summary: P = .079; SF-36, Mental Component Summary: P = .073). Side effects like
      dizziness, fatigue, or nausea were only mild to moderate. CONCLUSIONS:
      Levetiracetam is ineffective in the treatment of orthostatic tremor.

PMID- 21953631
TI  - Purification and characterization of an extracellular 24 kDa chitobiosidase from
      the mycoparasitic fungus Trichoderma saturnisporum.
AB  - A Trichoderma saturnisporum Hamill isolate GITX-Panog (C) exhibiting strong
      chitinolytic and antifungal activity against Fusarium oxysporum f.sp. dianthi,
      the causal agent of vascular wilt in carnation was used to purify extracellular
      chitobiosidase using Czapek-Dox broth amended with the fungal mycelium as the
      carbon source. The protein was purified by precipitation with ammonium sulphate,
      followed by DEAE-Cellulose anion-exchange and Sephacryl S-200 high resolution gel
      filtration chromatography. The purity of the enzyme was determined by SDS-PAGE,
      with an estimated molecular mass of 24 kDa. In native gel assay with 4
      methylumbelliferyl -N,N ' diacetyl-beta-D-chitobioside (4-Mu-(GluNAc)(2) , the
      purified chitobiosidase was visualized as single fluorescent band. Enzyme
      activity towards short oligomeric natural substrates indicated that the enzyme
      has properties that are characteristic to exochitinases. The enzyme was active up
      to 60  degrees C and at pH 4.0, and displayed maximum stability at 50  degrees C.
      Mn(2+) and Zn(2+) stimulated the enzyme activity by 63% and 41%, respectively.
      The K(m) and V(max) values of the purified enzyme for 4-Mu-(GluNAc)(2) were 338.9
      MUM ml(-1) and 0.119 MUM ml(-1) min(-1) , respectively. This appears to be the
      first report of characterization of a chitobiosidase from antagonistic
      Trichoderma saturnisporum.

PMID- 21953632
TI  - Electrophysiological indices of altered working memory processes in long-term
      ecstasy users.
AB  - OBJECTIVE: The aim of this study was to determine the effect of light long-term
      ecstasy consumption on verbal short-term and working memory and to identify the
      cognitive processes contributing to task performance. METHOD:
      Electroencephalogram was recorded while ecstasy users (N = 11), polydrug users (N
      = 13), and non-users (N = 13) completed forward and backward serial recognition
      tasks designed to engage verbal short-term memory and verbal working memory,
      respectively. RESULTS: All three groups displayed significantly lower digit
      backward span than digit-forward span with ecstasy users displaying the greatest
      difference. The parietally distributed P3b was significantly smaller in the
      digits backward task than in the digits forward task in non-ecstasy-using
      controls. Ecstasy users did not show the reduced P3b component in the backward
      task that was seen in both non-ecstasy-using control groups. CONCLUSIONS: Ecstasy
      users' performance was suppressed more by the concurrent processing demands of
      the working memory task than that of the non-ecstasy-using controls. Non-ecstasy
      using controls showed differential event-related potential wave forms in the
      short-term and working memory tasks, and this pattern was not seen in the ecstasy
      users. This is consistent with a reduction in the cognitive resources allocated
      to processing in working memory in ecstasy users.

PMID- 21953634
TI  - International consensus guidelines on anticardiolipin and anti-beta2-glycoprotein
      I testing: report from the 13th International Congress on Antiphospholipid
      Antibodies.

PMID- 21953633
TI  - Mature hepatocytes exhibit unexpected plasticity by direct dedifferentiation into
      liver progenitor cells in culture.
AB  - Although there have been numerous reports describing the isolation of liver
      progenitor cells from the adult liver, their exact origin has not been clearly
      defined; and the role played by mature hepatocytes as direct contributors to the
      hepatic progenitor cell pool has remained largely unknown. Here, we report strong
      evidence that mature hepatocytes in culture have the capacity to dedifferentiate
      into a population of adult liver progenitors without genetic or epigenetic
      manipulations. By using highly purified mature hepatocytes, which were obtained
      from untreated, healthy rat liver and labeled with fluorescent dye PKH2, we found
      that hepatocytes in culture gave rise to a population of PKH2-positive liver
      progenitor cells. These cells, liver-derived progenitor cells, which share
      phenotypic similarities with oval cells, were previously reported to be capable
      of forming mature hepatocytes, both in culture and in animals. Studies done at
      various time points during the course of dedifferentiation cultures revealed that
      hepatocytes rapidly transformed into liver progenitors within 1 week through a
      transient oval cell-like stage. This finding was supported by lineage-tracing
      studies involving double-transgenic AlbuminCreXRosa26 mice expressing beta
      galactosidase exclusively in hepatocytes. Cultures set up with hepatocytes
      obtained from these mice resulted in the generation of beta-galactosidase
      positive liver progenitor cells, demonstrating that they were a direct
      dedifferentiation product of mature hepatocytes. Additionally, these progenitors
      differentiated into hepatocytes in vivo when transplanted into rats that had
      undergone retrorsine pretreatment and partial hepatectomy. CONCLUSION: Our
      studies provide strong evidence for the unexpected plasticity of mature
      hepatocytes to dedifferentiate into progenitor cells in culture, and this may
      potentially have a significant effect on the treatment of liver diseases
      requiring liver or hepatocyte transplantation.

PMID- 21953635
TI  - Investigating cation binding in the polyoxometalate-super-crown [P8W48O184]40-.

PMID- 21953637
TI  - Fighting allergies beyond symptoms: the European Declaration on Immunotherapy.

PMID- 21953638
TI  - Extracellular proteolysis in macrophage migration: losing grip for a
      breakthrough.
AB  - Macrophage tissue infiltration is a hallmark of several pathological situations
      including cancer, neurodegenerative disorders and chronic inflammation. Hence,
      deciphering the mechanisms of macrophage migration across a variety of tissues
      holds great potential for novel anti-inflammatory therapies. Leukocytes have long
      been thought to migrate through tissues by using the amoeboid (protease
      independent) migration mode; however, recent evidence indicates that macrophages
      can use either the amoeboid or the mesenchymal (protease-dependent) migration
      mode depending on the environmental constraints. Proteolytic activity is required
      for several key processes including cell migration. Paradoxically, the role of
      proteases in macrophage migration has been poorly studied. Here, by focusing on
      the best characterized extracellular protease families - MMPs, cathepsins and
      urokinase-type plasminogen activator - we give an overview of their probable
      involvement in macrophage migration. These proteases appear to play a role in all
      of the situations encountered by migrating macrophages, i.e. diapedesis, 2D and
      3D migration. Migration of macrophages across tissues seems to proceed through an
      integrative analysis of numerous environmental clues allowing the cells to adapt
      their migration mode (amoeboid/mesenchymal) and secrete dedicated proteases to
      ensure efficient tissue infiltration, as discussed in this review. The role of
      proteases in macrophage migration is an emerging field of research, which
      deserves further work to allow a more precise understanding.

PMID- 21953639
TI  - New vistas on TLR9 activation.
AB  - Together with other reports, evidence published in this issue of the European
      Journal of Immunology by Avalos and Ploegh (Eur. J. Immunol. 2011. 41: 2820-2827)
      implies that trafficking of TLR9 from the ER to endolysosomal compartments, which
      is aided by the transmembrane UNC93B1 ER protein, is followed by proteolytic
      cleavage of the TLR9 ectodomain (TLR9ecto). Furthermore, Avalos and Ploegh
      elegantly show that RAW 264.7 macrophages stably expressing tagged TLR9 display
      significant amounts of cleaved TLR9 already when at rest. It is of note that
      inhibitory oligonucleotides (IN-ODNs) do not affect TLR9 cleavage but
      competitively prevent CpG-ligand binding to the C-terminal TLR9 fragment.
      Compared with phosphorothioated (PS) CpG-oligodeoxynucleotides (ODNs), natural
      phosphorodiester (PD) CpG-ODNs differ in their TLR9 activation efficiency. In
      this Commentary, a model is proposed that accounts for the differences in PS- and
      PD-ODNs with respect to TLR binding and activation.

PMID- 21953640
TI  - New insights into cathelicidin modulation of adaptive immunity.
AB  - Cathelicidins are a family of host defence peptides that are known to selectively
      alter innate immunity in response to infection and other changes in immune
      status. A study in this issue of the European Journal of Immunology elucidates a
      new role for mouse cathelin-related antimicrobial peptide in the adaptive immune
      response by clearly demonstrating for the first time that a cathelicidin can
      alter T-cell-dependent activation of the humoral response in vivo and thus
      modulate the activities of both B and T lymphocytes.

PMID- 21953644
TI  - Blastic plasmacytoid dendritic cell neoplasm.

PMID- 21953641
TI  - Regulation of the development of acute hepatitis by IL-23 through IL-22 and IL-17
      production.
AB  - IL-23 plays a critical role in the expansion of highly proinflammatory Th17 cells
      secreting IL-17 and IL-22. Recently, we demonstrated that Notch signaling drives
      IL-22 secretion through the aryl hydrocarbon receptor (AHR) and plays a
      protective role in Con A-induced hepatitis. In this study, we investigated the
      role of IL-23 in hepatitis using IL-23p19- and IL-17-deficient mice. In WT mice,
      the injection of Con A induced the upregulation of various cytokines, which
      included IL-23, IL-22, IL-17, IFN-gamma and TNF-alpha. In IL-23p19-deficient
      mice, exacerbated hepatitis was observed and serum IL-22 and IL-17 levels were
      greatly reduced, whereas in IL-17-deficient mice, ameliorated hepatitis was
      observed. The injection of exogenous IL-22 protected p19-deficient mice from
      hepatitis, whereas the injection of exogenous IL-23 significantly increased the
      serum levels of not only IL-22 but also IL-17, and less effectively protected
      against hepatitis in IL-17-dependent and -independent manners. Finally, it was
      revealed that STAT3, STAT4 and Notch contributed to the production of both the
      cytokines, and that the AHR was important only for IL-22 production in response
      to Con A and IL-23 in liver mononuclear cells. These results suggest that IL-23
      plays a protective role in hepatitis through IL-22 production and also a
      pathological role via IL-17-dependent and -independent mechanisms.

PMID- 21953645
TI  - Prescribing practices in a US cohort of rheumatoid arthritis patients before and
      after publication of the American College of Rheumatology treatment
      recommendations.
AB  - OBJECTIVE: To examine prescribing practices in the use of biologic and
      nonbiologic disease-modifying antirheumatic drugs (DMARDs) to treat patients with
      rheumatoid arthritis (RA), before and after publication of the American College
      of Rheumatology (ACR) treatment recommendations. METHODS: Biologics-naive RA
      patients under the care of a rheumatologist in the US were identified from the
      Consortium of Rheumatology Researchers of North America registry. Patients were
      included if their visits occurred prior to and/or at least 6 months after
      publication of the ACR treatment recommendations (time periods of February 2002
      June 2008 versus December 2008-December 2009). The population was divided into 2
      mutually exclusive cohorts: 1) methotrexate (MTX) monotherapy users, and 2)
      multiple nonbiologic DMARD users. Initiation or dose escalation of biologic and
      nonbiologic DMARDs in response to active disease was assessed cross-sectionally
      and longitudinally in comparison to the ACR recommendations. The impact of the
      publication of the ACR recommendations on treatment practices was assessed using
      logistic regression, stratified by disease activity and adjusted for clustering
      of physicians and geographic region. RESULTS: After 1 visit, 24-37% of patients
      receiving MTX monotherapy who had moderate disease activity and a poor prognosis
      or high disease activity received care consistent with the ACR recommendations;
      after 2 visits, 34-56% of the MTX monotherapy group received care consistent with
      the recommendations. In the patients receiving multiple nonbiologic DMARDs, 31
      47% of those with moderate or high disease activity received care consistent with
      the recommendations after 1 visit, and 43-51% received such care after 2 visits.
      Publication of the recommendations did not significantly change treatment
      patterns for those with active disease. CONCLUSION: Substantial numbers of RA
      patients with active disease did not receive care consistent with the current ACR
      treatment recommendations. Innovative approaches to improve care are necessary.

PMID- 21953646
TI  - MiR-17/106b seed family regulates p21 in Hodgkin's lymphoma.
AB  - Hodgkin's lymphoma (HL) is a B cell-derived lymphoma characterized by a minority
      of malignant Hodgkin Reed-Sternberg (HRS) cells that have lost their normal B
      cell phenotype. Alterations in the cell cycle and apoptosis pathways might
      contribute to their resistance to apoptosis and sustained cell cycle progression.
      A key player in both cell cycle arrest and apoptosis is CDKN1A, encoding
      p21$^{{?rm{waf/cip1}}}$ (p21). P21 is regulated by p53 and can function as a cell
      cycle inhibitor when in the nucleus or as an apoptosis inhibitor when localized
      in the cytoplasm. We observed expression of p53, p21 and p-p21 in a variable
      number of HRS cells in 24 of 40 cases. Expression of miR-17 and miR-106a was
      detected in HRS cells of 10 HL cases. MiR-17/106b seed family members, CDKN1A RNA
      and p21 protein levels were variable in HL cell lines. We showed effective
      targeting of the CDKN1A 3' UTR by miR-17/106b in HL cell lines in a luciferase
      reporter assay and up-regulation of p21 protein levels upon anti-miR-17 treatment
      of KM-H2 cells. Functional studies indicated a p21-mediated G(1) arrest after miR
      17/106b down-regulation in KM-H2, whereas no G(1) arrest was observed for U-HO1
      and L428. This difference could not be explained by differences in the 3' UTR,
      the cellular location of p21 or expression variation during cell cycle
      progression. A strong correlation was observed for the miR-17/106b:CDKN1A ratio
      and the responsiveness to miR-17 inhibition, ie a low ratio in KM-H2 and an
      extremely high ratio in the two unresponsive HL cell lines. In conclusion, we
      show that miR-17/106b regulates p21 protein levels in HL and that the effect of
      miR-17/106b-mediated inhibition depends on the miRNA : target gene ratio. Thus,
      in HL high miR-17/106b expression contributes to a dysfunctional p53 pathway and
      thereby also to the malignant phenotype.

PMID- 21953647
TI  - Drosophila as a model of wound healing and tissue regeneration in vertebrates.
AB  - Understanding the molecular basis of wound healing and regeneration in
      vertebrates is one of the main challenges in biology and medicine. This
      understanding will lead to medical advances allowing accelerated tissue repair
      after wounding, rebuilding new tissues/organs and restoring homeostasis.
      Drosophila has emerged as a valuable model for studying these processes because
      the genetic networks and cytoskeletal machinery involved in epithelial movements
      occurring during embryonic dorsal closure, larval imaginal disc
      fusion/regeneration, and epithelial repair are similar to those acting during
      wound healing and regeneration in vertebrates. Recent studies have also focused
      on the use of Drosophila adult stem cells to maintain tissue homeostasis. Here,
      we review how Drosophila has contributed to our understanding of these processes,
      primarily through live-imaging and genetic tools that are impractical in mammals.
      Furthermore, we highlight future research areas where this insect may provide
      novel insights and potential therapeutic strategies for wound healing and
      regeneration.

PMID- 21953648
TI  - Ten-year survival of esophageal cancer after an en-bloc esophagectomy.
AB  - BACKGROUND: Esophagectomy with gastric pull-up is the optimal treatment for
      patients with resectable esophageal cancer. Although the morbidity and mortality
      of an esophagectomy is reduced, the long-term outcome remains poor. The aim of
      this study was to evaluate the 10-year survival of a standardized
      multidisciplinary therapy concept for esophageal cancer. METHODS: Between 1989
      and 1999, 114 patients were treated for esophageal cancer at the University of
      Essen. All patients underwent an en-bloc esophagectomy with systematic
      lymphadenectomy. Patients with locally advanced disease (stage III) received
      neoadjuvant therapy. All patients were followed-up for 10 years or more or until
      death. RESULTS: The 3-year survival was 35%, the 5-year survival 25%, and the 10
      year survival was 18%. The recurrence rate was 44% with a median time of 13
      months. There was no significant difference in survival between patients with
      locally advanced disease who received neoadjuvant therapy and patients with early
      disease (stadium I + II) who underwent surgery alone. Of the patients who
      achieved 10-year survival, 60% had locally advanced disease and received
      neoadjuvant therapy. CONCLUSION: Patients with locally advanced disease, managed
      by a multidisciplinary treatment strategy, achieved a similar long-term survival
      to patients with early disease (stadium I + II).

PMID- 21953650
TI  - Linear-scaling soft-core scheme for alchemical free energy calculations.
AB  - Alchemical free energy calculations involving the removal or insertion of atoms
      into condensed phase systems generally make use of soft-core scaling of nonbonded
      interactions, designed to circumvent numerical instabilities that arise from
      weakly interacting "hard" atoms in close proximity. Current methods model soft
      core atoms by introducing a nonlinear dependence between the shape of the
      interaction potential and the strength of the interaction. In this article, we
      propose a soft-core method that avoids introducing such a nonlinear dependence,
      through the application of a smooth flattening of the potential energy only in a
      region that is energetically accessible under normal conditions. We discuss the
      benefits that this entails and explore a selection of applications, including
      enhanced methods for the estimation of free energy differences and for the
      automated optimization of the placement of intermediate states in multistage
      alchemical calculations.

PMID- 21953649
TI  - An in vitro, short-term culture method for mammalian haploid round spermatids
      amenable for molecular manipulation.
AB  - Extensive chromatin remodeling is a characteristic feature of mammalian
      spermiogenesis. To date, methods for the molecular manipulation of haploid
      spermatids are not available as there is a lack of a well-established culture
      system. Biochemical experiments and knockout studies reveal only the final
      outcome; studying the incremental details of the intricate mechanisms involved is
      still a challenge. We have established an in vitro culture system for pure
      haploid round spermatids isolated from rat testes that can be maintained with
      good viability for up to 72 hr. Changes in cell morphology and flagellar growth
      were also studied in the cultured spermatids. Further, we have demonstrated that
      upon treatment of cells with specific histone deacetylase inhibitors, sodium
      butyrate and trichostatin A, there is an increase in the hyperacetylation status
      of histone H4, mimicking an important event characteristic of histone replacement
      process that occurs during later stages of spermiogenesis. We have also tried
      various methods for introducing DNA and protein into these round spermatids in
      culture, and report that while DNA transfection is still a challenging task,
      protein transfection could be achieved using ChariotTM peptide as a transfection
      reagent. Thus, the method described here sets a stage to study the molecular
      roles of spermatid-specific proteins and chromatin remodelers in the cellular
      context.

PMID- 21953651
TI  - Determination of enalapril and enalaprilat in small human serum quantities for
      pediatric trials by HPLC-tandem mass spectrometry.
AB  - The angiotensin converting enzyme-inhibitor enalapril is the prodrug of
      enalaprilat and used in the treatment pediatric hypertension and chronic heart
      failure. Pharmacokinetic data are lacking to provide adequate dosing and for
      pediatric pharmacotherapeutical trials it is imperative to minimize sample
      volume. Therefore an HPLC-tandem mass spectrometry (MS) method for the
      determination of enalapril and enalaprilat in 100 MUL of human serum was
      developed and validated with benazepril as internal standard (IS). After solid
      phase extraction, chromatography was performed on a Luna((r)) RP-C(18) (2) column
      with methanol-water-formic acid (65:35:1, v/v/v) as mobile phase and a flow rate
      of 0.4 mL/min. The MS was set to positive-mode electrospray ionization and
      multiple reaction monitoring, analyzing the m/z transitions channels 377.3 ->
      234.2, 349.3 -> 206.1 and 425.3 -> 351.2 for enalapril, enalaprilat and IS.
      Calibration curves were linear in the range of 1.61-206 ng/mL (enalapril) and
      1.84-236 ng/mL (enalaprilat) with coefficients of determination >0.99. Relative
      standard deviations of intra- and inter-run precisions were below 7% and relative
      errors were below 6 +/- 7% for both analytes. Also stabilities were acceptable
      for both analytes. As an application example, concentrations of enalapril and
      enalaprilat in serum after oral administration of 20 mg enalapril maleat in a
      healthy volunteer were determined.

PMID- 21953652
TI  - On the need for scholarly practitioners in CPD.

PMID- 21953653
TI  - Pharmacist Web-based training program on medication use in chronic kidney disease
      patients: impact on knowledge, skills, and satisfaction.
AB  - INTRODUCTION: Chronic kidney disease (CKD) patients are multimorbid elderly at
      high risk of drug-related problems. A Web-based training program was developed
      based on a list of significant drug-related problems in CKD patients requiring a
      pharmaceutical intervention. The objectives were to evaluate the impact of the
      program on community pharmacists' knowledge and skills and their satisfaction
      with the training. METHODS: Pharmacists were randomized to the training program
      or the control group. Training comprised a 60-minute Web-based interactive
      session supported by a clinical guide. Pharmacists completed a questionnaire on
      knowledge (10 multiple-choice questions) and skills (2 clinical vignettes) at
      baseline and a second time within 1 month. Trained pharmacists completed a
      written satisfaction questionnaire. Semidirected telephone interviews were
      conducted with 8 trained pharmacists. Changes in knowledge and skills scores were
      compared between the groups. RESULTS: Seventy pharmacists (training: 52; control:
      18) were recruited; the majority were women with <15 years' experience. Compared
      with the control group, an adjusted incremental increase in the knowledge score
      (22%; 95% confidence interval [CI]: 16%-27%) and skills score (24%; 95% CI: 16%
      33%) was observed in the training group. Most pharmacists (87%-100%) rated each
      aspect of the program "excellent'' or "very good." Additional training and adding
      a discussion forum were suggested to complement the program. DISCUSSION:
      Pharmacists like the Web-based continuing education program. Over a short time
      span, the program improved their knowledge and skills. Its impact on their
      clinical practices and quality of medication use in CKD patients remains to be
      assessed.

PMID- 21953654
TI  - Moving into medical practice in a new community: the transition experience.
AB  - INTRODUCTION: Physicians undertake many transitions during the course of a
      medical career. The purpose of this study was to explore the experiences of
      physicians who moved to a new community. METHODS: A semistructured interview
      format was used to explore transitional experiences, including reasons for
      moving; the role of colleagues, learning, and organizational structures; how
      various mediating factors affected perceptions; and how the experience affected
      the physicians personally. We used qualitative methods in which data were
      collected, coded, and analyzed concurrently. RESULTS: 20 physicians from family
      medicine, internal medicine, and pediatrics described their experiences. Both the
      professional context and the geographic location affected physicians' perceptions
      of the move. Both internal and external mediating factors appeared to influence
      how physicians experienced and adjusted to the move. Physicians who joined
      functioning units appeared to have fewer problems. The physicians who had more
      difficulty were physicians who did not come to a specific job, often coming as
      the result of a spousal move; did not have a professional network in the city;
      had not sorted out licensure requirements; and were entering community (not
      institutional) practice. DISCUSSION: This study demonstrates the critical nature
      of institutional support structures to integrate the newcomer, collegial
      relationships within the workplace, and the importance of family and friends in
      mediating the adjustment period. Consideration should be given to structured
      mentorship or peer-buddy programs and longitudinal educational programs (eg,
      rounds) that may enable physicians to establish networks and gain practical local
      knowledge quickly.

PMID- 21953655
TI  - Confidence-based learning CME: overcoming barriers in irritable bowel syndrome
      with constipation.
AB  - INTRODUCTION: Performance of health care professionals depends on both medical
      knowledge and the certainty with which they possess it. Conventional continuing
      medical education interventions assess the correctness of learners' responses but
      do not determine the degree of confidence with which they hold incorrect
      information. This study describes the use of confidence-based learning (CBL) in
      an activity designed to enhance learners' knowledge, confidence in their
      knowledge, and clinical competence with regard to constipation-predominant IBS
      (IBS-C), a frequently underdiagnosed and misdiagnosed condition. METHODS: The
      online CBL activity included multiple-choice questions in 2 modules: Burden of
      Care (BOC; 28 questions) and Patient Scenarios (PS; 9 case-based questions).
      After formative assessment, targeted feedback was provided, and the learner
      focused on material with demonstrated knowledge and/or confidence gaps. The
      process was repeated until 85% of questions were answered correctly and
      confidently (ie, mastery was attained). RESULTS: Of 275 participants (24%
      internal medicine, 13% gastroenterology, 32% family medicine, and 31% other), 249
      and 167 completed the BOC and PS modules, respectively. Among all participants,
      61.8% and 98.2% achieved mastery in the BOC and PS modules, respectively.
      Baseline mastery levels between specialties were significantly different in the
      BOC module (p = 0.002); no significant differences were evident between
      specialties in final mastery levels. Approximately one-third of learners were
      confident and wrong in topics of epidemiology, defining IBS and constipation, and
      treatments in the first iteration. No significant difference was observed between
      specialties for the PS module in either the first or last iterations. DISCUSSION:
      Learners achieved mastery in topics pertaining to IBS-C regardless of baseline
      knowledge or specialty. These data indicate that CME activities employing CBL can
      be used to address knowledge and confidence gaps.

PMID- 21953656
TI  - CPD and KT: a special collaboration.

PMID- 21953657
TI  - CPD and KT: models used and opportunities for synergy.
AB  - The two fields of continuing professional development (CPD) and knowledge
      translation (KT) within the health care sector, and their related research have
      developed as somewhat parallel paths with limited points of overlap or
      intersection. This is slowly beginning to change. The purpose of this paper is to
      describe and compare the dominant conceptual models informing each field with the
      view of increasing understanding and appreciation of the two fields, how they are
      similar and where they differ, and the current and potential points of
      intersection. The models include the "knowledge-to-action'' (KTA) cycle informing
      KT, models informing CPD curriculum design and individual self-directed learning,
      and the Kirkpatrick model for evaluating educational outcomes. When compared
      through the perspectives of conceptual designs, processes, and outcomes, the
      models overlap. We also identify shared gaps in both fields (eg, the need to
      explore the influence of the context in which CPD and KT interventions take
      place) and suggest opportunities for synergies and for moving forward.

PMID- 21953658
TI  - Knowledge translation research: the science of moving research into policy and
      practice.
AB  - Research findings will not change health outcomes unless health care
      organizations, systems, and professionals adopt them in practice. Knowledge
      translation research is the scientific study of the methods to promote the uptake
      of research findings by patients, health care providers, managers, and policy
      makers. Many forms of enquiry addressing different questions are needed to
      develop the evidence base for knowledge translation. In this paper we will
      present a description of the broad scope of knowledge translation research with a
      reflection on activities needed to further develop the science of knowledge
      translation. Consideration of some of the shared research challenges facing the
      fields of knowledge translation and continuing professional development will also
      be presented.

PMID- 21953659
TI  - Partnerships for knowledge translation and exchange in the context of continuing
      professional development.
AB  - Continuing professional development (CPD) is an important vehicle for knowledge
      translation (KT); however, selecting CPD strategies that will impact health
      professionals' behavior and improve patient outcomes is complex. In response, we,
      KT researchers and CPD knowledge users, have recently formed a partnership known
      as the National Network for Patient-Centered Evidence-Based Continuing
      Professional Development. The partnership was initiated in 2006 with a series of
      CIHR Knowledge Translation: Planning, Meetings and Dissemination grants. The
      objectives of these grants were to bring members of the CPD and KT communities
      together, determine their interest in working together, identify similarities and
      differences in the fields of CPD and KT, and develop working groups to inform
      larger collaborative initiatives to support knowledge translation and exchange.
      The vision for this partnership is to become a premiere knowledge translation
      collaboration and a cutting-edge implementation network that informs the
      provision of CPD across Canada and abroad. This paper reports on the development
      and outcomes of this network to date.

PMID- 21953660
TI  - Using film in multicultural and social justice faculty development: scenes from
      Crash.
AB  - We designed a faculty development workshop integrating scene excerpts from the
      Academy Award-winning movie Crash and active learning methods to encourage
      faculty participation and generate participant dialogue. The aims of this
      workshop were to enhance awareness of issues related to teaching in a
      multicultural classroom; stimulate discussion on teaching and learning about
      potentially contentious issues linked to race, ethnicity, religion, gender,
      geographical origin, and class; and expose faculty to the use of multimedia to
      facilitate discussion on topics of diversity and social justice. Twenty-five
      faculty attended 3 workshops in various venues, 18 of whom completed workshop
      evaluations. The workshop evaluation revealed that all participants believed that
      the scene excerpts and discussions helped them to reflect on their own attitudes
      toward race and diversity and felt better prepared to effectively facilitate
      classroom discussions on similar issues. This workshop is a useful tool for
      helping faculty to develop the skills and confidence to facilitate, manage, and
      stimulate discussions on controversial issues in multicultural education that may
      otherwise be avoided due to lack of expertise or experience.

PMID- 21953661
TI  - Educating clinicians about cultural competence and disparities in health and
      health care.
AB  - An extensive body of literature has documented significant racial and ethnic
      disparities in health and health care. Cultural competency interventions,
      including the training of physicians and other health care professionals, have
      been proposed as a key strategy for helping to reduce these disparities. The
      continuing medical education (CME) profession can play an important role in
      addressing this need by improving the quality and assessing the outcomes of
      multicultural education programs. This article provides an overview of health
      care policy, legislative, accreditation, and professional initiatives relating to
      these subjects. The status of CME offerings on cultural competence/disparities is
      reviewed, with examples provided of available curricular resources and online
      courses. Critiques of cultural competence training and selected studies of its
      effectiveness are discussed. The need for the CME profession to become more
      culturally competent in its development, implementation, and evaluation of
      education programs is examined. Future challenges and opportunities are
      described, and a call for leadership and action is issued.

PMID- 21953662
TI  - Integrating essential components of quality improvement into a new paradigm for
      continuing education.
AB  - Continuing education (CE) that strives to improve patient care in a complex
      health care system requires a different paradigm than CE that seeks to improve
      clinician knowledge and competence in an educational setting. A new paradigm for
      CE is necessary in order to change clinician behavior and to improve patient
      outcomes in an increasingly patient-centered, quality-oriented care context. The
      authors assert that a new paradigm should focus attention on an expanded and
      prioritized list of educational outcomes, starting with those that directly
      affect patients. Other important components of the paradigm should provide
      educational leaders with guidance about what interventions work, reasons why
      interventions work, and what contextual factors may influence the impact of
      interventions. Once fully developed, a new paradigm will be helpful to educators
      in designing and implementing more effective CE, an essential component of
      quality improvement efforts, and in supporting policy trends and in promoting CE
      scholarship. The purpose of this article is to rekindle interest in CE theory and
      to suggest key components of a new paradigm.

PMID- 21953663
TI  - "Friending Facebook?" A minicourse on the use of social media by health
      professionals.
AB  - INTRODUCTION: Health professionals are working in an era of social technologies
      that empower users to generate content in real time. This article describes a 3
      part continuing education minicourse called "Friending Facebook?" undertaken at
      Penn State Hershey Medical Center that aimed to model the functionality of
      current technologies in health care and encourage discussion about how health
      professionals might responsibly utilize social media. METHODS: Fifteen health
      professionals participated in the course and provided written evaluation at its
      conclusion. The course instructor took field notes during each of the 3 classes
      to document emergent themes. RESULTS: The course received uniformly positive
      evaluations, and participants identified several current tools perceived as being
      potentially useful in their professional lives, including news aggregators,
      Google Alerts, and--if used responsibly--social networking sites such as
      Facebook. DISCUSSION: Developing innovative and appropriate programming that
      teaches to emerging social media technologies and ideologies will be crucial to
      helping the health professions adapt to a new, networked era. Medical
      institutions would do well to foster interprofessional-and perhaps even
      intergenerational-conversations to share not only the dangers and risks of social
      media, but also the opportunities that are emerging out of a rapidly evolving
      online world.

PMID- 21953664
TI  - A mixed-methods, multiprofessional approach to needs assessment for designing
      education.

PMID- 21953665
TI  - Prisoners holding their own medications during imprisonment in England and Wales:
      a survey and qualitative exploration of staff and prisoners' views.
AB  - BACKGROUND: Traditionally, medication in prison has been administered in single,
      supervised doses. Prisons in England and Wales, however, have now been encouraged
      to allow prisoners to hold and manage their own medication themselves as 'in
      possession' medication, in line with community practices. AIMS: We aimed to
      examine the range of policies and practices used to manage in-possession
      medication in prisons, and to explore staff and patient perspectives. METHODS: A
      mixed methods design was selected. Questionnaires were sent to all prisons
      throughout England and Wales in 2008, and follow-up interviews were completed
      with 68 staff and 24 patients at 12 prisons. RESULTS: In-possession medication
      was permitted to some degree within all prisons. Interviewees identified its
      principal benefit in terms of empowerment, whilst acknowledging the need to
      minimise health and security risks. Structured methods of risk assessment were
      used in 93% of establishments, although content and structure varied widely.
      CONCLUSION: There is still some way to go before in-possession medication
      policies are fully embraced in prisons. Staff and patients recognise its
      benefits, but some remain uneasy around the perceived risks. Risk management
      processes in some establishments may still require development. KEY MESSAGES:
      Prisoners and staff generally find it acceptable for prisoners to have their own
      medication in their possession, to manage themselves, unless individual risk
      assessment indicates otherwise. Achievement of the optimum balance between
      security, safety and empowering patients is difficult in practice. Robust,
      specific methods of risk management in relation to in-possession medication may
      help prisons move from being 'risk averse' to 'risk aware'.

PMID- 21953666
TI  - Malaria--one swallow makes a summer.

PMID- 21953669
TI  - Replacing alkoxy groups with alkylthienyl groups: a feasible approach to improve
      the properties of photovoltaic polymers.

PMID- 21953670
TI  - Highly conducting coordination polymers based on infinite M(4,4'-bpy) chains
      flanked by regular stacks of non-integer TCNQ radicals.

PMID- 21953671
TI  - Asymmetric total synthesis of the epoxykinamycin FL-120 B'.

PMID- 21953673
TI  - Sunitinib-induced changes in circulating endothelial cell-related proteins in
      patients with metastatic renal cell cancer.
AB  - Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors
      are effective agents in the treatment of metastatic renal cell cancer (mRCC). We
      here investigated whether inhibition of VEGFR signalin by sunitinib causes
      changes in plasma proteins associated with tumor endothelium. Forty-three
      patients with mRCC received sunitinib 50 mg/day in a 4-weeks on 2-weeks off
      schedule. Sequential plasma samples were obtained before treatment (C1D1), on
      C1D14, on C1D28, and on C2D1 before start of cycle 2. Plasma levels were assessed
      for VEGF, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble
      intercellular cell adhesion molecule-1 (sICAM-1), von Willebrand factor (vWF),
      circulating angiopoietin-2 (Ang-2) and soluble Tie-2 (sTie-2). Total tumor burden
      was calculated at baseline and at first evaluation. Progression-free survival
      (PFS) and overall survival (OS) were determined. Tumor burden was positively
      associated with baseline circulating Ang-2 [Spearman's rho (rho) = 0.378, p =
      0.028] and vWF (rho = 0.417, p = 0.008). During sunitinib treatment, circulating
      Ang-2 and sTie-2 significantly decreased (p < 0.001 for both), plasma levels of
      sVCAM-1 and VEGF significantly increased (p = 0.022 and p < 0.001), whereas those
      of sICAM-1 and vWF remained stable. These protein changes had recovered on C2D1.
      The reduction in circulating Ang-2 levels on C1D28 was positively correlated with
      the percentage decrease in tumor burden (rho = 0.605; p = 0.002). Baseline
      protein levels and subsequent changes were not associated with PFS or OS. In
      conclusion, sunitinib-induced changes in Ang-2, sTie-2, sVCAM-1 and VEGF are
      related to the administration schedule, while reduction in Ang-2 is also
      associated with decrease in tumor burden.

PMID- 21953674
TI  - Alumina-coated patterned amorphous silicon as the anode for a lithium-ion battery
      with high coulombic efficiency.

PMID- 21953675
TI  - Biosynthesis and characterization of Au-nanostructures by metal tolerant fungi.
AB  - Microorganisms being eco-friendly and encompassing special features are widely
      employed in the biosynthesis of different metal nanoparticles (NPs). In the
      present study, the potential of different fungal strains has been explored for
      the synthesis of various morphologies of gold nanostructures. Preliminary
      confirmation of nanosized particles formation has been done with visual
      observation as the synthesized gold nanoparticles exhibited a variety of colours
      covering whole visible spectra. Crystallographic and morphological
      characterization of synthesized nano-materials associated with different fungal
      strains have been done using X-ray diffraction (XRD) and transmission electron
      microscope (TEM). Nanoparticles morphology dependence on different fungal strains
      has been studied and described in detail. A wide variation in shape and size of
      gold nanoparticles with different strains has been reported as a function of
      strain characteristics.

PMID- 21953676
TI  - A 1,2,3,4,5-pentaphenylferrocene-stoppered rotaxane capable of electrochemical
      anion recognition.
AB  - The chloride anion templated synthesis of an electrochemical anion sensory
      interlocked host system, prepared by the integration of redox-active 1,2,3,4,5
      pentaphenylferrocene stopper groups into the structure of a rotaxane capable of
      binding anionic guests is described. Extensive (1)H NMR and electrochemical
      titration investigations were used to probe the anion recognition and sensing
      properties of the rotaxane, compared to the axle and model system components. A
      characteristic electrochemical response was observed for chloride binding by the
      rotaxane, which was attributed to the topologically constrained cavity of the
      interlocked host molecule.

PMID- 21953679
TI  - Reinnervation of urethral and anal sphincters with femoral motor nerve to
      pudendal nerve transfer.
AB  - AIMS: Lower motor neuron damage to sacral roots or nerves can result in
      incontinence and a flaccid urinary bladder. We showed bladder reinnervation after
      transfer of coccygeal to sacral ventral roots, and genitofemoral nerves (L1, 2
      origin) to pelvic nerves. This study assesses the feasibility of urethral and
      anal sphincter reinnervation using transfer of motor branches of the femoral
      nerve (L2-4 origin) to pudendal nerves (S1, 2 origin) that innervate the urethral
      and anal sphincters in a canine model. METHODS: Sacral ventral roots were
      selected by their ability to stimulate bladder, urethral sphincter, and anal
      sphincter contraction and transected. Bilaterally, branches of the femoral nerve,
      specifically, nervus saphenous pars muscularis [Evans HE. Miller's anatomy of the
      dog. Philadelphia: W.B. Saunders; 1993], were transferred and end-to-end
      anastomosed to transected pudendal nerve branches in the perineum, then enclosed
      in unipolar nerve cuff electrodes with leads to implanted RF micro-stimulators.
      RESULTS: Nerve stimulation induced increased anal and urethral sphincter
      pressures in five of six transferred nerves. Retrograde neurotracing from the
      bladder, urethral sphincter, and anal sphincter using fluorogold, fast blue, and
      fluororuby, demonstrated urethral and anal sphincter labeled neurons in L2-4 cord
      segments (but not S1-3) in nerve transfer canines, consistent with reinnervation
      by the transferred femoral nerve motor branches. Controls had labeled neurons
      only in S1-3 segments. Postmortem DiI and DiO labeling confirmed axonal regrowth
      across the nerve repair site. CONCLUSIONS: These results show spinal cord
      reinnervation of urethral and anal sphincter targets after sacral ventral root
      transection and femoral nerve transfer (NT) to the denervated pudendal nerve.
      These surgical procedures may allow patients to regain continence.

PMID- 21953680
TI  - Long-term follow-up of polytetrafluoroethylene-covered stents implanted during
      percutaneous coronary intervention for management of acute coronary perforation.
AB  - OBJECTIVE: To determine the long-term outcomes for patients receiving
      polytetrafluoroethylene (PTFE)-covered stents as definitive therapy, in our
      institution, for the management of acute coronary perforation. BACKGROUND:
      Coronary perforation as a complication of percutaneous coronary intervention
      (PCI) is associated with high morbidity and mortality. Management options
      included observation only or a combination of several or all of these approaches:
      reversal of anticoagulation, prolonged balloon inflation, deployment of a
      standard stent, emergent cardiac surgery, or insertion of a PTFE-covered stent.
      METHODS: With our IRB approval, records of 12,093 consecutive patients who
      received PCI during a 5-year period from January 2002 to December 2006 were
      reviewed and 50 patients who had coronary perforation as a complication of PCI
      were identified. RESULTS: Of the 21 patients who received a PTFE-covered stent to
      manage coronary perforation, one died secondary to acute thrombosis within the
      PTFE-covered stent in the first 24 hrs and one required emergent cardiac surgery
      due to continued contrast extravasation despite PTFE-covered stent deployment.
      The other 19 patients were followed long term (mean 55 months) and only one
      survivor had a potentially life-threatening outcome (subacute stent thrombosis)
      over that time period. CONCLUSION: Utilization of a PTFE-covered stent may be a
      reasonable short- and long-term option to manage acute coronary perforation that
      occurs during PCI. On the basis of this limited experience, successful PTFE
      covered stent deployment as the conclusive treatment for coronary perforation is
      associated with a favorable long-term event-free survival rate.

PMID- 21953682
TI  - Sex differences in sleep after a single oral morning dose of olanzapine in
      healthy volunteers.
AB  - OBJECTIVE: Polysomnography abnormalities are frequent in schizophrenia and have
      been correlated with clinical variables. Because women with schizophrenia present
      a general better clinical outcome than men, we aimed to determine whether sex
      differences in antipsychotic-induced effects on sleep could contribute to this
      difference. METHODS: Single oral morning doses of olanzapine (5 mg) were
      administered to 10 men and 10 women. Sleep variables were evaluated using
      traditional polysomnography Rechstschaffen and Kales criteria and all-night sleep
      electroencephalogram spectral analysis. Drug plasma concentrations were also
      measured. RESULTS: Significant sex-by-drug interactions were obtained in slow
      wave sleep. After olanzapine, women showed an increase in slow-wave sleep,
      whereas men showed a decrease. We did not observe sex differences in olanzapine
      induced hypnotic effects. Neither did we find any significant differences in
      pharmacokinetic parameters between sexes. Significant sex effects were observed
      in deep sleep, with women showing longer periods than men. CONCLUSION: Our
      results showed significant pharmacodynamic differences in olanzapine sleep
      effects between men and women. Further studies in clinical populations are needed
      to assess if these sex-based differences suggest that optimal treatment and doses
      should differ between men and women.

PMID- 21953681
TI  - A mouse model of accelerated liver aging caused by a defect in DNA repair.
AB  - The liver changes with age, leading to an impaired ability to respond to hepatic
      insults and increased incidence of liver disease in the elderly. Therefore, there
      is critical need for rapid model systems to study aging-related liver changes.
      One potential opportunity is murine models of human progerias or diseases of
      accelerated aging. Ercc1(-/Delta) mice model a rare human progeroid syndrome
      caused by inherited defects in DNA repair. To determine whether hepatic changes
      that occur with normal aging occur prematurely in Ercc1(-/Delta) mice, we
      systematically compared liver from 5-month-old progeroid Ercc1(-/Delta) mice to
      old (24-36-month-old) wild-type (WT) mice. Both displayed areas of necrosis, foci
      of hepatocellular degeneration, and acute inflammation. Loss of hepatic
      architecture, fibrosis, steatosis, pseudocapillarization, and anisokaryosis were
      more dramatic in Ercc1(-/Delta) mice than in old WT mice. Liver enzymes were
      significantly elevated in serum of Ercc1(-/Delta) mice and old WT mice, whereas
      albumin was reduced, demonstrating liver damage and dysfunction. The regenerative
      capacity of Ercc1(-/Delta) liver after partial hepatectomy was significantly
      reduced. There was evidence of increased oxidative damage in Ercc1(-/Delta) and
      old WT liver, including lipofuscin, lipid hydroperoxides and acrolein, as well as
      increased hepatocellular senescence. There was a highly significant correlation
      in genome-wide transcriptional changes between old WT and 16-week-old, but not 5
      week-old, Ercc1(-/Delta) mice, emphasizing that the Ercc1(-/Delta) mice acquire
      an aging profile in early adulthood. CONCLUSION: There are strong functional,
      regulatory, and histopathological parallels between accelerated aging driven by a
      DNA repair defect and normal aging. This supports a role for DNA damage in
      driving aging and validates a murine model for rapidly testing hypotheses about
      causes and treatment for aging-related hepatic changes.

PMID- 21953683
TI  - Age-related cerebral perfusion changes in the parietal and temporal lobes
      measured by pulsed arterial spin labeling.
AB  - PURPOSE: To investigate age-related regional perfusion changes focused on the
      medial temporal lobes and related parietal areas using a pulsed arterial spin
      labeling technique. MATERIALS AND METHODS: Resting cerebral blood flow (CBF) maps
      were obtained from 44 healthy volunteers (18 male, 26 female; age range, 19 to 79
      years) using a pulsed arterial spin labeling (PASL) MRI technique at 3 Tesla
      focused on the parietal and temporal lobes. Repeated measurements were performed
      in 20 subjects to assure the reliability and reproducibility of the applied PASL
      technique. RESULTS: Focal age-related CBF decreases were detected in the parietal
      cortex, cuneus and caudate, whereas increases were seen in the lateral and medial
      temporal lobe such as hippocampus, the calcarine gyrus and the thalamus.
      Moreover, repeated measurements demonstrated a high reliability and
      reproducibility of the applied PASL technique. CONCLUSION: Data provide evidence
      for regionally dissociated patterns of perfusion increases and decreases during
      ageing in the temporal and parietal lobes.

PMID- 21953684
TI  - Effects of benzene and its metabolites on global DNA methylation in human normal
      hepatic L02 cells.
AB  - Benzene is an important industrial chemical that is also widely present in
      cigarette smoke, automobile exhaust, and gasoline. It is reported that benzene
      can cause hematopoietic disorders and has been recognized as a human carcinogen.
      However, the mechanisms by which it increases the risk of carcinogenesis are only
      partially understood. Aberrant DNA methylation is a major epigenetic mechanism
      associated with the toxicity of carcinogens. To understand the carcinogenic
      capacity of benzene, experiments were designed to investigate whether exposure to
      benzene and its metabolites would change the global DNA methylation status in
      human normal hepatic L02 cells and then to evaluate whether the changes would be
      induced by variation of DNA methyltransferase (DNMT) activity in HaeIII DNMT
      mediated methylation assay in vitro. Our results showed that hydroquinone and 1,4
      benzoquinone could induce global DNA hypomethylation with statistically
      significant difference from control (p < 0.05), but no significant global DNA
      methylation changes were observed in L02 cells with benzene, phenol, and 1,2,4
      trihydroxybenzene exposure. Benzene metabolites could not influence HaeIII DNMT
      activity except that 1,4-benzoquinone shows significantly inhibiting effect on
      enzymatic methylation reaction at concentrations of 5 MUM (p < 0.05). These
      results suggest that benzene metabolites, hydroquinone, and 1,4-benzoquinone can
      disrupt global DNA methylation, and the potential epigenetic mechanism by which
      that global DNA hypomethylation induced by 1,4-benzoquinone may work through the
      inhibiting effects of DNMT activity at 10 MUM (p < 0.05).

PMID- 21953685
TI  - Facile and general synthesis of photoactivatable xanthene dyes.

PMID- 21953686
TI  - Diagnosis of systemic lupus erythematosus from a bone marrow aspirate.

PMID- 21953688
TI  - A validated Fourier transform infrared spectroscopy method for quantification of
      total lactones in Inula racemosa and Andrographis paniculata.
AB  - INTRODUCTION: Fourier transform infrared (FT-IR) spectroscopy is a technique
      widely used for detection and quantification of various chemical moieties. This
      paper describes the use of the FT-IR spectroscopy technique for the
      quantification of total lactones present in Inula racemosa and Andrographis
      paniculata. OBJECTIVE: To validate the FT-IR spectroscopy method for
      quantification of total lactones in I. racemosa and A. paniculata. METHODOLOGY:
      Dried and powdered I. racemosa roots and A. paniculata plant were extracted with
      ethanol and dried to remove ethanol completely. The ethanol extract was analysed
      in a KBr pellet by FT-IR spectroscopy. The FT-IR spectroscopy method was
      validated and compared with a known spectrophotometric method for quantification
      of lactones in A. paniculata. RESULTS: By FT-IR spectroscopy, the amount of total
      lactones was found to be 2.12 +/- 0.47% (n = 3) in I. racemosa and 8.65 +/- 0.51%
      (n = 3) in A. paniculata. The method showed comparable results with a known
      spectrophotometric method used for quantification of such lactones: 8.42 +/-
      0.36% (n = 3) in A. paniculata. Limits of detection and quantification for
      isoallantolactone were 1 ug and 10 ug respectively; for andrographolide they were
      1.5 ug and 15 ug respectively. Recoveries were over 98%, with good intra- and
      interday repeatability: RSD <= 2%. CONCLUSION: The FT-IR spectroscopy method
      proved linear, accurate, precise and specific, with low limits of detection and
      quantification, for estimation of total lactones, and is less tedious than the UV
      spectrophotometric method for the compounds tested. This validated FT-IR
      spectroscopy method is readily applicable for the quality control of I. racemosa
      and A. paniculata.

PMID- 21953689
TI  - Application of molecular dynamics simulations in molecular property prediction
      II: diffusion coefficient.
AB  - In this work, we have evaluated how well the general assisted model building with
      energy refinement (AMBER) force field performs in studying the dynamic properties
      of liquids. Diffusion coefficients (D) have been predicted for 17 solvents, five
      organic compounds in aqueous solutions, four proteins in aqueous solutions, and
      nine organic compounds in nonaqueous solutions. An efficient sampling strategy
      has been proposed and tested in the calculation of the diffusion coefficients of
      solutes in solutions. There are two major findings of this study. First of all,
      the diffusion coefficients of organic solutes in aqueous solution can be well
      predicted: the average unsigned errors and the root mean square errors are 0.137
      and 0.171 * 10(-5) cm(-2) s(-1), respectively. Second, although the absolute
      values of D cannot be predicted, good correlations have been achieved for eight
      organic solvents with experimental data (R(2) = 0.784), four proteins in aqueous
      solutions (R(2) = 0.996), and nine organic compounds in nonaqueous solutions
      (R(2) = 0.834). The temperature dependent behaviors of three solvents, namely,
      TIP3P water, dimethyl sulfoxide, and cyclohexane have been studied. The major
      molecular dynamics (MD) settings, such as the sizes of simulation boxes and
      with/without wrapping the coordinates of MD snapshots into the primary simulation
      boxes have been explored. We have concluded that our sampling strategy that
      averaging the mean square displacement collected in multiple short-MD simulations
      is efficient in predicting diffusion coefficients of solutes at infinite
      dilution.

PMID- 21953690
TI  - Composition and architecture of biofilms on used voice prostheses.
AB  - BACKGROUND: Biofilms on medical devices are a frequent reason for failure of the
      device. Voice prostheses in laryngectomized patients deteriorate within 3 to 4
      months due to adhering biofilms, impeding proper functioning. Recently, we showed
      that these biofilms are dominated by Candida and lactobacilli. However, the early
      report of this finding lacked an in depth analysis of the species diversity and
      community structure. METHODS: Denaturing gradient gel electrophoresis (DGGE) and
      sequence analysis of amplified rRNA genes was used to identify microorganisms.
      Fluorescence in situ hybridization (FISH) was used to analyze biofilm
      architecture. RESULTS: Candida are the predominant fungi in the biofilms, while
      lactobacilli are the predominant bacteria in all investigated biofilms, followed
      by streptococci. FISH shows that lactobacilli and streptococci seem to have an
      important interaction with fungi. CONCLUSION: The results give a better
      understanding of biofilm formation and can be used in further development to
      prevent biofilm formation on voice prostheses.

PMID- 21953691
TI  - How to manage vaccinations in children with cancer.
AB  - The optimal use of routine childhood immunizations in children with malignancy is
      still a matter of debate. Despite their higher risk of contracting vaccine
      preventable diseases and of suffering important complications, there is little
      understanding of the magnitude of the possible benefit of administering active
      immunization in this population due to a paucity of clinical trial data. Our
      review focuses on the management of children with cancer and offers some
      suggestions regarding their vaccination schedules.

PMID- 21953692
TI  - An uncommon morphological variant of acute promyelocytic leukemia.

PMID- 21953693
TI  - Treatment of dysarthria following subthalamic nucleus deep brain stimulation for
      Parkinson's disease.
AB  - BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an
      established treatment for patients with Parkinson's disease (PD). Speech
      impairment is a frequent side effect of the surgery. This study examined the
      efficacy of an intensive speech treatment, the Lee Silverman Voice Treatment
      (LSVT) on dysarthria after STN-DBS. METHODS: The LSVT was administered to 10
      patients with STN-DBS (surgical group) and 10 patients without (medical group).
      Patients were assessed before, immediately after, and 6 months following the
      speech treatment using sustained phonation, a speech intelligibility scale, and
      monologue. Vocal loudness, speech intelligibility, and perceptual ratings were
      the primary outcome measures. RESULTS: Vocal loudness and perceptual scores
      improved significantly across tasks for the medical group only. Speech
      intelligibility did not significantly change for either group. Results in the
      surgical group were variable, with some patients deteriorating. CONCLUSIONS:
      Treatment of dysarthria following STN-DBS needs further investigation because of
      the variable response to LSVT.

PMID- 21953694
TI  - Potassium silanide (KSiH3): a reversible hydrogen storage material.
AB  - KSi silicide can absorb hydrogen to directly form the ternary KSiH(3) hydride.
      The full structure of alpha-KSiD(3), which has been solved by using neutron
      powder diffraction (NPD), shows an unusually short Si-D lengths of 1.47 A.
      Through a combination of density functional theory (DFT) calculations and
      experimental methods, the thermodynamic and structural properties of the
      KSi/alpha-KSiH(3) system are determined. This system is able to store 4.3 wt% of
      hydrogen reversibly within a good P-T window; a 0.1 MPa hydrogen equilibrium
      pressure can be obtained at around 414 K. The DFT calculations and the
      measurements of hydrogen equilibrium pressures at different temperatures give
      similar values for the dehydrogenation enthalpy (~23 kJ mol(-1) H(2)) and entropy
      (~54 J K(-1) mol(-1) H(2)). Owing to its relatively high hydrogen storage
      capacity and its good thermodynamic values, this KSi/alpha-KSiH(3) system is a
      promising candidate for reversible hydrogen storage.

PMID- 21953695
TI  - Photoprotection by dietary carotenoids: concept, mechanisms, evidence and future
      development.
AB  - Carotenoids are micronutrients present mainly in fruits and vegetables, and they
      are ingested from these sources with the diet. They exhibit specific antioxidant
      activity but also influence signaling and gene expression at the cellular level.
      beta-Carotene and lycopene, the colorants of carrots and tomatoes, respectively,
      are among the most prominent members of this group of lipids, and they are
      usually the dominating carotenoids in human blood and tissues. Both compounds
      modulate skin properties when ingested as supplements or as dietary products.
      There is evidence that they protect the skin against sunburn (solar erythema) by
      increasing the basal defense against UV light-mediated damage. Their
      photoprotective efficacy, however, is not comparable to the use of a sunscreen.
      In vitro data show that also other carotenoids are efficient photoprotectors.
      Among them are lutein and structurally unusual phenolic polyenes like 3,3'
      dihydroxyisorenieratene.

PMID- 21953698
TI  - Oxidative carbonylation reactions: organometallic compounds (R-M) or hydrocarbons
      (R-H) as nucleophiles.
AB  - Oxidative carbonylation reactions have attracted broad interest from both
      academia and industry in recent years. Enormous efforts have gone into the
      syntheses of carbonate and urea derivatives through the oxidative carbonylation
      of alcohols and amines. Very recently, organometallic reagents (R-M) and
      hydrocarbons(R-H) were directly employed as nucleophiles to construct a C-C bond
      in oxidative carbonylation reactions. This Minireview summarizes this novel type
      of oxidative carbonylation reaction.

PMID- 21953696
TI  - The neurexin ligands, neuroligins and leucine-rich repeat transmembrane proteins,
      perform convergent and divergent synaptic functions in vivo.
AB  - Synaptic cell adhesion molecules, including the neurexin ligands, neuroligins
      (NLs) and leucine-rich repeat transmembrane proteins (LRRTMs), are thought to
      organize synapse assembly and specify synapse function. To test the synaptic role
      of these molecules in vivo, we performed lentivirally mediated knockdown of NL3,
      LRRTM1, and LRRTM2 in CA1 pyramidal cells of WT and NL1 KO mice at postnatal day
      (P)0 (when synapses are forming) and P21 (when synapses are largely mature). P0
      knockdown of NL3 in WT or NL1 KO neurons did not affect excitatory synaptic
      transmission, whereas P0 knockdown of LRRTM1 and LRRTM2 selectively reduced AMPA
      receptor-mediated synaptic currents. P0 triple knockdown of NL3 and both LRRTMs
      in NL1 KO mice yielded greater reductions in AMPA and NMDA receptor-mediated
      currents, suggesting functional redundancy between NLs and LRRTMs during early
      synapse development. In contrast, P21 knockdown of LRRTMs did not alter
      excitatory transmission, whereas NL manipulations supported a role for NL1 in
      maintaining NMDA receptor-mediated transmission. These results show that neurexin
      ligands in vivo form a dynamic synaptic cell adhesion network, with compensation
      between NLs and LRRTMs during early synapse development and functional divergence
      upon synapse maturation.

PMID- 21953699
TI  - Enhancement of the capability of hydroxyapatite formation on Zr with anodic ZrO2
      nanotubular arrays via an effective dipping pretreatment.
AB  - Hydroxyapatite (HA) depositions on metallic biomedical implants are widely
      applied to generate bioactive surfaces in simulated biological environments.
      Highly ordered anodic ZrO2 nanotubes have attracted increasing interest for
      biomedical applications. However, previous reports showed that at least 14-28
      days were required to obtain HA coating on ZrO2 nanotubular arrays under
      biomimetic condition, thus capability to grow HA coating on ZrO 2nanotubular at
      room temperature needs to be enhanced. In the present work, we demonstrate that
      ZrO2 nanotubular arrays are suitable for an effective dipping treatment to induce
      more rapid HA coating. A series of ZrO2 nanotubular arrays having different
      dimensions were fabricated in fluoride containing electrolyte. Then, we used a
      dipping treatment for biomimetic formation of an adhesive HA coating on the
      nanotubular arrays. The coatings formed rapidly using this procedure under
      biomimetic conditions and did not require a high-temperature annealing process.
      The as-formed ZrO2 nanotubular arrays were treated using several dip-and-dry
      steps, through which the nanotubular arrays were filled and covered with calcium
      phosphate (CaP) nucleation sites. The specimens readily grew HA once immersed in
      the simulated biological fluid after 2 days immersion. The carbonated HA coating
      had several micron thickness after 8 days of immersion while only a thin layer of
      CaP were observed on annealed ZrO2 nanotubes immersed in the same solution for
      the same duration. Tensile testing showed that bonding strength between HA
      coating and substrate was 21.6 +/- 1.6 MPa. This treatment dramatically improves
      efficiency for promoting HA formation on anodic ZrO2 nanotubes at room
      temperature.

PMID- 21953697
TI  - Ubiquitin ligase Nedd4 promotes alpha-synuclein degradation by the endosomal
      lysosomal pathway.
AB  - alpha-Synuclein is an abundant brain protein that binds to lipid membranes and is
      involved in the recycling of presynaptic vesicles. In Parkinson disease, alpha
      synuclein accumulates in intraneuronal inclusions often containing ubiquitin
      chains. Here we show that the ubiquitin ligase Nedd4, which functions in the
      endosomal-lysosomal pathway, robustly ubiquitinates alpha-synuclein, unlike
      ligases previously implicated in its degradation. Purified Nedd4 recognizes the
      carboxyl terminus of alpha-synuclein (residues 120-133) and attaches K63-linked
      ubiquitin chains. In human cells, Nedd4 overexpression enhances alpha-synuclein
      ubiquitination and clearance by a lysosomal process requiring components of the
      endosomal-sorting complex required for transport. Conversely, Nedd4 down
      regulation increases alpha-synuclein content. In yeast, disruption of the Nedd4
      ortholog Rsp5p decreases alpha-synuclein degradation and enhances inclusion
      formation and alpha-synuclein toxicity. In human brains, Nedd4 is present in
      pigmented neurons and is expressed especially strongly in neurons containing Lewy
      bodies. Thus, ubiquitination by Nedd4 targets alpha-synuclein to the endosomal
      lysosomal pathway and, by reducing alpha-synuclein content, may help protect
      against the pathogenesis of Parkinson disease and other alpha-synucleinopathies.

PMID- 21953700
TI  - Mechanical control of nanomaterials and nanosystems.
AB  - In situations of power outage or shortage, such as periods just following a
      seismic disaster, the only reliable power source available is the most
      fundamental of forces i.e., manual mechanical stimuli. Although there are many
      macroscopic mechanical tools, mechanical control of nanomaterials and nanosystems
      has not been an easy subject to develop even by using advanced nanotechnological
      concepts. However, this challenge has now become a hot topic and many new ideas
      and strategies have been proposed recently. This report summarizes recent
      research examples of mechanical control of nanomaterials and nanosystems.
      Creation of macroscopic mechanical outputs by efficient accumulation of molecular
      level phenomena is first briefly introduced. We will then introduce the main
      subject: control of molecular systems by macroscopic mechanical stimuli. The
      research described is categorized according to the respective areas of mechanical
      control of molecular structure, molecular orientation, molecular interaction
      including cleavage and healing, and biological and micron-level phenomena.
      Finally, we will introduce two more advanced approaches, namely, mechanical
      strategies for microdevice fabrication and mechanical control of molecular
      machines. As mechanical forces are much more reliable and widely applicable than
      other stimuli, we believe that development of mechanically responsive
      nanomaterials and nanosystems will make a significant contribution to fundamental
      improvements in our lifestyles and help to maintain and stabilize our society.

PMID- 21953701
TI  - Validity and reliability of a Turkish version of the body shape questionnaire
      among female high school students: preliminary examination.
AB  - The aim of this study is to assess the validity and reliability of a Turkish
      version of the Body Shape Questionnaire (BSQ) among young people. The BSQ was
      initially administrated to female high school students (N = 665) and administered
      a second time to a subset of subjects (N = 144). The subjects also completed the
      Eating Attitudes Test, the Body Image Satisfaction Questionnaire (a dieting
      questionnaire) and the Hopkins Symptom Checklist (SCL-90), and were weighed, and
      their body mass indices were calculated. Test-retest reliability of the BSQ was
      0.81. The BSQ score correlated highly with the Eating Attitudes Test, Body Image
      Satisfaction Questionnaire and the Hopkins Symptom Checklist. Higher BSQ scores
      were also associated with higher body mass index. The results suggest that the
      Turkish version of BSQ is a valid and reliable tool for assessing body image
      concerns in teenagers.

PMID- 21953702
TI  - Stroke due to late device thrombosis following successful percutaneous patent
      foramen ovale closure.
AB  - We report a case of stroke due to device thrombosis occurring three years
      following percutaneous patent foramen ovale (patent foramen ovale) closure with
      an Amplatzer atrial septal occluder device. We discuss risk factors that may have
      contributed to device thrombosis and raise concerns regarding the lack of a
      dedicated PFO closure device for clinical use in the United States.

PMID- 21953703
TI  - Fluorescence of 1,2-diaminoanthraquinone and its nitric oxide reaction product
      within macrophage cells.
AB  - Nitric oxide (NO) is involved in many biological processes. Aromatic ortho
      diamine derivatives are commonly used in the fluorescence imaging of NO in living
      cells. ortho-diamino (o-diamino) compounds are believed to react with NO in an
      oxygenated medium leading to the formation of a triazole derivative. One such o
      diamino compound, 1,2-diaminoanthraquinone (DAA), is a nontoxic probe for the
      detection of NO in living tissues and cells. The formation of the DAA triazole
      derivative (DAA-TZ) upon reaction of DAA with NO/O(2)  within cells has not been
      demonstrated previously. The aim of this study was to confirm that DAA-TZ is the
      species formed intracellularly when DAA reacts with NO in the presence of oxygen.
      The chemical synthesis and characterisation of DAA-TZ was performed together with
      intracellular studies of DAA and DAA-TZ. Raw 264.7 macrophages were loaded with
      the DAA or DAA-TZ under conditions of no-stimulation or stimulation with
      interferon-gamma and lipopolysaccharide to produce NO. Confocal microscopy was
      used to image the DAA-loaded macrophage cells. Analysis of the emission spectra
      allowed precise discrimination of the fluorescence of each species in the
      macrophage cells, and confirmed the identity of DAA-TZ as the intracellular
      reaction product between DAA and NO in the presence of oxygen.

PMID- 21953704
TI  - Ecstasy use and self-reported disturbances in sleep.
AB  - OBJECTIVE: Ecstasy users report a number of complaints after its use including
      disturbed sleep. However, little is known regarding which attributes of ecstasy
      use are associated with sleep disturbances, which domains of sleep are affected
      or which factors may predict those ecstasy users likely to have poor sleep
      quality and/or excessive daytime sleepiness. METHODS: This study examined
      questionnaire responses of social drug users (n = 395) to the Pittsburgh Sleep
      Quality Index and the Epworth Sleepiness Scale. RESULTS: A significant proportion
      of ecstasy users (69.5%) had Pittsburgh Sleep Quality Index scores above the
      threshold used to identify sleep disturbance. Although frequency of ecstasy use
      did not affect the degree of reported sleep disturbance, participants who used
      larger amounts of ecstasy had poorer sleep. In addition, participants who
      perceived harmful consequences arising from their ecstasy use or had experienced
      remorse following ecstasy use had poorer sleep. Clinically relevant levels of
      sleep disturbance were still evident after controlling for polydrug use. Risk
      factors for poor sleep quality were younger age, injury post-ecstasy use and
      having been told to cut down on ecstasy use. CONCLUSIONS: Many ecstasy users
      report poor sleep quality, which likely contributes to the negative effects
      reported following ecstasy use.

PMID- 21953705
TI  - Mechanisms involved in endothelin-1-induced contraction of the pig urinary
      bladder neck.
AB  - AIMS: There is no information about the signaling pathways involved in the
      endothelin-1 (ET-1)-induced contraction of bladder neck. The current study
      investigates the mechanisms involved in the ET-1-elicited contraction in the pig
      bladder neck. METHODS: Bladder neck strips were mounted in organ baths containing
      physiological saline solution at 37 degrees C and gassed with 95% O(2) and 5%
      CO(2) , for isometric force recording to endothelin receptor agonists,
      noradrenaline (NA), and electrical field stimulation. Endothelin ET(A) receptor
      expression was also determined, by both immunohistochemistry and Western blot.
      RESULTS: ET(A) receptor expression (Western blot) was observed in the muscular
      layer and urothelium. A strong ET(A) -immunoreactivity (ET(A) -IR) was identified
      within nerve fibers among smooth muscle bundles. ET-1 and ET-2 evoked similar
      concentration-dependent contractions of urothelium-denuded preparations. ET-3
      produced a slight response, whereas the ET(B) receptor agonist BQ3020 failed to
      promote contraction. BMS182874, an ET(A) receptor antagonist, reduced ET-1
      induced contraction whereas BQ788, an ET(B) antagonist, did not change such
      responses. ET-1 contractions were reduced by extracellular Ca(2+) removal and by
      inhibition of voltage-gated Ca(2+) (VOC) (L-type) and non-VOC channels, Rho/Rho
      kinase pathway, and neuronal VOC channels. NA produced contractions which were
      enhanced by ET-1 threshold concentrations. ET(A) receptor blockade enhanced
      nitric oxide-dependent nerve-mediated relaxations. CONCLUSIONS: These results
      suggest that ET-1 produces contraction via muscular ET(A) receptors coupled to
      extracellular Ca(2+) entry via VOC (L-type) and non-VOC channels. Intracellular
      Ca(2+) mobilization and a Rho/Rho-kinase pathway could also be involved in these
      responses. ET-1-evoked potentiation on noradrenergic contraction, and neuronal
      ET(A) receptors modulating nitrergic inhibitory neurotransmission, are also
      demonstrated.

PMID- 21953706
TI  - Effect of J-coupling on lipid composition determination with localized proton
      magnetic resonance spectroscopy at 9.4 T.
AB  - PURPOSE: To demonstrate, at 9.4 T, that J-coupling interactions exhibited by
      lipid protons affects lipid composition determination with a point resolved
      spectroscopy (PRESS) sequence. MATERIALS AND METHODS: Experiments were conducted
      on four oils (almond, corn, sesame, and sunflower), on visceral adipose tissue of
      a euthanized mouse, and on pure linoleic acid at 9.4 T. The 2.1, 2.3, and 2.8 ppm
      resonances were measured at multiple echo times (TEs) by a standard PRESS
      sequence and by a PRESS sequence consisting of narrow-bandwidth refocusing pulses
      designed to rewind the J-coupling evolution of the target peak protons in the
      voxel of interest. T(2) corrections were performed on both groups of data for the
      three peaks and lipid compositions for the oils and for the mouse tissue were
      determined. Lipid compositions were also calculated from a short-TE standard
      PRESS spectrum. RESULTS: A chemical analysis of the samples was not performed;
      however, the oil compositions calculated from resonance peaks acquired with the
      PRESS sequence designed to minimize J-coupling effects, following T(2) relaxation
      correction, closely agreed with values in the literature, which was not the case
      for all of the compositions determined from the regular PRESS spectra.
      CONCLUSION: The presented work brings to attention the significance of J-coupling
      effects when calculating lipid compositions from localized proton spectra.

PMID- 21953707
TI  - Oleanolic acid prevents glucocorticoid-induced hypertension in rats.
AB  - The present study was designed to evaluate the antihypertensive activity of
      oleanolic acid isolated from Viscum articulatum, Burm. (Loranthaceae) in
      glucocorticoid (dexamethasone)-induced hypertension in rats and to propose a
      probable mechanism of action for this effect. Male Wistar rats (300-350 g)
      received dexamethasone (20 MUg/kg/day s.c.) or saline (vehicle) for 10 days. In a
      prevention study, the rats received oleanolic acid (60 mg/kg i.p.) for 5 days,
      followed by dexamethasone or saline for 10 days. During this period the systolic
      blood pressure and body weight were evaluated on alternate days. At the end of
      the experiment, the weight of the thymus gland, plasma nitrate/nitrite (nitric
      oxide metabolites) concentration and cardiac lipid peroxidation value were
      determined. Oleanolic acid (60 mg/kg i.p.) significantly prevented a rise in the
      systolic blood pressure and cardiac lipid peroxidation level after administration
      of dexamethasone (p < 0.01 and p < 0.05, respectively) without showing any
      significant effect on the dexamethasone-induced change in body and thymus
      weights. The decrease in concentration of plasma nitrate/nitrite due to
      dexamethasone was prevented significantly in the group treated with oleanolic
      acid (p < 0.05). These findings suggest that oleanolic acid (60 mg/kg i.p.)
      prevents dexamethasone-induced hypertension in rats, which may be attributed to
      its antioxidant and nitric oxide releasing action.

PMID- 21953708
TI  - Common responses in gene expression by Ephedra herba in brain and heart of mouse.
AB  - The physiological activities of Ephedra herba have been investigated extensively,
      particularly in the cardiovascular and cerebrovascular systems. However, the
      molecular mechanisms underlying the effects of Ephedra herba on the brain and
      heart have yet to be thoroughly elucidated at the whole genome level. Therefore,
      the present study focused on the identification of the regulatory pattern of gene
      expression occurring in response to Ephedra herba, using microarray assays in
      three mouse organs - namely, the brain, heart and liver. Interestingly, the brain
      and heart exhibited a similar reciprocal pattern of gene expression during the
      early stages after the administration of Ephedra herba, whereas the liver
      evidenced a different gene expression profile. Moreover, pathways analysis showed
      that genes regulated reciprocally by Ephedra herba were associated with neural
      disease-related functions, such as the Parkinson's disease pathway, in both the
      brain and the heart. Promoter sequence analysis demonstrated that reciprocally
      regulated genes could be classified into subgroups on the basis of the similarity
      of their transcription factor binding sequences, in which temporally up-regulated
      genes were clustered as distinctive subgroups. In conclusion, the brain and heart
      responded commonly to Ephedra herba with a temporally reciprocal pattern of gene
      expression.

PMID- 21953709
TI  - HPLC fingerprint of a flower extract of Tilia * viridis and correlation with
      antiproliferative and antioxidant activity.
AB  - Tilia species have been used in Europe and in America to treat anxiety and also
      for the treatment of colds, influenza, bronchitis, fever and inflammation. Tilia
      * viridis is a Tilia species distributed widely in Buenos Aires, Argentina. The
      flavonoids present in Tilia species have antioxidant properties, acting as
      reactive oxygen species (ROS) scavengers, principally on hydrogen peroxide
      (H(2)O(2)) and the superoxide anion (O(2)(.-)), which are involved in many
      diseases, including cancer. The aim of this study was to determine the
      phytochemical pattern of the ethanol extract of Tilia * viridis, principally the
      flavonoid content, and to evaluate the antiproliferative effects on both normal
      and tumoral cells, and the antioxidant activity in relation to H(2)O(2)
      modulation. The extract was found to present a selective antiproliferative
      activity on a lymphoma cell line and this was related to free radical scavenging
      activity. In addition, one of its main compounds, rutin, showed antioxidant
      effects related to peroxidase activity. T. * viridis may therefore be a source of
      antioxidant compounds that contribute to a selective antiproliferative action on
      tumoral cells, acting by modulation of H(2)O(2) levels.

PMID- 21953710
TI  - Genome wide expression analysis of the effect of the Chinese patent medicine
      Zilongjin tablet on four human lung carcinoma cell lines.
AB  - Zilongjin (ZLJ) tablet, which is a traditional Chinese medicine, has been
      approved as a new anti-tumor drug by the State Food and Drug Administration of
      China; however, its anti-cancer mechanisms remain elusive. The goal of this study
      was to investigate the underlying anti-cancer activities of ZLJ tablet in vitro.
      In this study, four lung cancer cell lines, A549, H446, H460 and H520, were
      treated with 2.2 mg/mL of ZLJ solution for 24 h at 37  degrees C under 5% CO(2) .
      RNA was isolated and a microarray experiment using the Affymetrix Human Genome
      U133 plus 2.0 Array was employed to differentiate the expression patterns of
      cancer-related genes after drug treatment. Of 483 genes in 63 functional
      categories and 25 different pathways that showed at least a 2-fold change of
      expression level in the four cancer cell lines, 170 genes were upregulated, and
      313 genes were downregulated. Eleven of the 483 genes were cancer-related and
      belong to the three known pathways: apoptosis, cell cycle regulation and mitogen
      activated protein kinase (MAPK) cascade. The microarray data were validated by
      real-time RT-PCR. The results of this investigation suggest possible anti-cancer
      mechanisms of the ZLJ tablet, and lay a foundation to further analyse its
      therapeutic roles.

PMID- 21953711
TI  - 6-gingerol prevents patulin-induced genotoxicity in HepG2 cells.
AB  - Patulin (PAT) is a mycotoxin produced by several Penicillium, Aspergillus and
      Byssochlamys species. Since PAT is a potent genotoxic compound, and PAT
      contamination is common in fruits and fruit products, the search for newer,
      better agents for protection against genotoxicity of PAT is required. In this
      study, the chemoprotective effect of 6-gingerol against PAT-induced genotoxicity
      in HepG2 cells was investigated. The comet assay and micronucleus test (MNT) were
      used to monitor genotoxic effects. To further elucidate the underlying
      mechanisms, the intracellular generation of reactive oxygen species (ROS) and
      level of reduced glutathione (GSH) were tested. In addition, the level of
      oxidative DNA damage was evaluated by immunocytochemical analysis of 8
      hydroxydeoxyguanosine (8-OHdG). The results showed that 6-gingerol significantly
      reduced the DNA strand breaks and micronuclei formation caused by PAT. Moreover,
      6-gingerol effectively suppressed PAT-induced intracellular ROS formation and 8
      OHdG level. The GSH depletion induced by PAT in HepG2 cells was also attenuated
      by 6-gingerol pretreatment. These findings suggest that 6-gingerol has a strong
      protective ability against the genotoxicity caused by PAT, and the antioxidant
      activity of 6-gingerol may play an important part in attenuating the genotoxicity
      of PAT.

PMID- 21953713
TI  - The end of the beginning: a commentary on 'Evaluation metrics for biostatistical
      and epidemiological collaborations'.
AB  - The paper 'Evaluation Metrics for Biostatistical and Epidemiological
      Collaborations' of Rubio et al. represents an important initial advance in the
      evaluation of biostatistics, epidemiology, and research design (BERD). The
      authors present a sensible three-domain model (collaboration with investigators,
      application of BERD-related methods, and discovery of new BERD methodologies),
      rightly acknowledge the importance of team science, and break new ground in
      illustrating that the Clinical Translational Science Awards can function as a
      kind of national laboratory for the development and exploration of measures and
      metrics. Building upon these gains, there are several future considerations
      worthy of subsequent serious attention: strengthening the connection between BERD
      evaluation and both the science of team science and the field of evaluation;
      facing the challenges of operationalization of the conceptual domains; augmenting
      the work of Rubio et al. with standard evaluative models; and anticipating the
      need for multiplistic mixed methods and experimental and quasi-experimental
      complements to the proposed BERD metrics. Several common pitfalls will also be
      important to avoid, including the tendency to conflate the meaning of 'metrics'
      and 'measures' and the potential for a premature rush to adopt national
      'standards' before adequately pilot testing the initial set of methods they have
      worked so diligently to develop.

PMID- 21953715
TI  - Hierarchically assembled ZnO nanocrystallites for high-efficiency dye-sensitized
      solar cells.

PMID- 21953712
TI  - Oncogene addiction as a foundational rationale for targeted anti-cancer therapy:
      promises and perils.
AB  - A decade has elapsed since the concept of oncogene addiction was first proposed.
      It postulates that - despite the diverse array of genetic lesions typical of
      cancer - some tumours rely on one single dominant oncogene for growth and
      survival, so that inhibition of this specific oncogene is sufficient to halt the
      neoplastic phenotype. A large amount of evidence has proven the pervasive power
      of this notion, both in basic research and in therapeutic applications. However,
      in the face of such a considerable body of knowledge, the intimate molecular
      mechanisms mediating this phenomenon remain elusive. At the clinical level,
      successful translation of the oncogene addiction model into the rational and
      effective design of targeted therapeutics against individual oncoproteins still
      faces major obstacles, mainly due to the emergence of escape mechanisms and drug
      resistance. Here, we offer an overview of the relevant literature, encompassing
      both biological aspects and recent clinical insights. We discuss the key
      advantages and pitfalls of this concept and reconsider it as an illustrative
      principle to guide post-genomic cancer research and drug development.

PMID- 21953718
TI  - Wilms tumor in Africa: challenges to cure.

PMID- 21953719
TI  - Role of surface iron in enhanced activity for the oxygen reduction reaction on a
      Pd3Fe(111) single-crystal alloy.

PMID- 21953720
TI  - Effect of storage time and conditions on the diene valepotriates content of the
      extract of Valeriana glechomifolia obtained by supercritical carbon dioxide.
AB  - INTRODUCTION: Valepotriates (epoxy iridoid esters) represent an important group
      of constituents that contribute to pharmacological effects for the genus
      Valeriana. Storage and extraction of valepotriates is a demanding task, as these
      compounds are thermolabile and unstable: even when decomposition products are not
      formed, isovaleric acid liberation from the iridoid nucleus originate compounds
      with less complex substituents. OBJECTIVE: To study the influence of time and
      storage conditions on the diene valepotriates (valtrate, isovaltrate,
      acevaltrate, 1-beta-acevaltrate, 1-beta-aceacevaltrate) content of the Valeriana
      glechomifolia (native to southern Brazil), extract was obtained by supercritical
      fluid extraction using CO2 as the fluid (SF-CO2). METHODOLOGY: Above-ground and
      below-ground material of V. glechomifolia was extracted by SF-CO2 (40  degrees C,
      90 bar). The extract was stored under nitrogen atmosphere or solubilised in
      methanol. Valepotriates stability was accessed during storage at -20  degrees C
      over 8 months through reverse-phase HPLC (mobile phase acetonitrile:water 50:50
      (v/v); 254 nm). RESULTS: A gradual increase in valtrate levels and decrease in
      acevaltrate, 1-beta-acevaltrate and 1-beta-aceacevaltrate, concentration were
      observed from the first month of storage for the dry extract. However, for the
      methanol solubilised extract these changes occurred only after the third month
      and were accompanied by reduction in isovaltrate levels and formation of
      decomposition products. CONCLUSION: SF-CO2 showed high selectivity for
      valepotriates extraction. This is the first report on valepotriates molecular
      conversion, which was less accelerated when the extract was stored in methanol,
      but under this condition degradation products are also present, probably
      baldrinals, that are not observed in the dry extract.

PMID- 21953721
TI  - Pharyngoesophageal stricture after treatment for head and neck cancer.
AB  - BACKGROUND: The purpose of this study was to report the risk of
      pharyngoesophageal stricture after treatment for head and neck cancer. METHODS:
      Human studies on radiation therapy with or without chemotherapy for head and neck
      cancer published in peer-reviewed journals with assessment of pharyngoesophageal
      stricture with barium swallow or endoscopy were included. RESULTS: A total of
      4727 patients from 26 studies treated between 1989 and 2008 were eligible for
      analysis. The reported overall risk of stricture was 7.2%. The risks of
      pharyngoesophageal stricture in both conventional and intensity-modulated
      radiation therapy (IMRT) studies were 5.7% and 16.7%, respectively (p < .001).
      Use of concurrent (p < .001) and taxane (p = .01) chemotherapy was associated
      with the IMRT technique. Prospective studies reported a 3.3-fold increased risk
      of stricture compared with that of retrospective studies (odds ratio: 3.3; 95%
      confidence interval: 2.3-4.8; p < .001). CONCLUSIONS: Pharyngoesophageal
      stricture after IMRT and chemotherapy treatment for head and neck cancer is not
      uncommon. Videofluoroscopic swallow study should be performed prospectively to
      evaluate swallowing function.

PMID- 21953722
TI  - Diagnosis of a primary cardiac B-cell lymphoma.

PMID- 21953723
TI  - In Situ one-step electrochemical preparation of graphene oxide nanosheet-modified
      electrodes for biosensors.

PMID- 21953724
TI  - The p.S77N presenilin-associated rhomboid-like protein mutation is not a frequent
      cause of early-onset Parkinson's disease.

PMID- 21953725
TI  - Viscosity gradient as a novel mechanism for the centrifugation-based separation
      of nanoparticles.

PMID- 21953726
TI  - New silica monolith bonded chiral (R)-gamma butyrolactone for enantioselective
      micro high-performance liquid chromatography.
AB  - A single low-molecular mass chiral selector namely (R)-acryloyloxy-beta-beta
      dimethyl-gamma-butyrolactone has been bonded to a modified silica-based monolith
      to form a new brush-type chiral stationary phase for micro-high performance
      liquid chromatography (HPLC) separation.

PMID- 21953727
TI  - Cogrinding significance for calcium carbonate-calcium phosphate mixed cement. II.
      Effect on cement properties.
AB  - In the present study, we aim to evaluate the contribution of the cogrinding
      process in controlling calcium carbonate-dicalcium phosphate dihydrate cement
      properties. We set a method designed to evaluate phase separation, usually
      occurring during paste extrusion, which is quantitative, reliable, and
      discriminating and points out the determining role of cogrinding to limit filter
      pressing. We show that solid-phase cogrinding leads to synergistic positive
      effects on cement injectability, mechanical properties, and radio-opacity. It
      allows maintaining a low (<0.4 kg) and constant load during the extrusion of
      paste, and the paste's composition remains constant and close to that of the
      initial paste. Analogous behavior was observed when adding a third component into
      the solid phase, especially SrCO(3) as a contrasting agent. Moreover, the
      cement's mechanical properties can be enhanced by lowering the L/S ratio because
      of the lower plastic limit. Finally, unloaded or Sr-loaded cements show uniform
      and increased optical density because of the enhanced homogeneity of dry
      component distribution. Interestingly, this study reveals that cogrinding
      improves and controls essential cement properties and involves processing
      parameters that could be easily scaled up. This constitutes a decisive advantage
      for the development of calcium carbonate-calcium phosphate mixed cements and,
      more generally, of injectable multicomponent bone cements that meet a surgeon's
      requirements.

PMID- 21953728
TI  - Cocoa-rich diet prevents azoxymethane-induced colonic preneoplastic lesions in
      rats by restraining oxidative stress and cell proliferation and inducing
      apoptosis.
AB  - Cocoa is a rich source of bioactive compounds with potential chemopreventive
      ability but up to date its effectiveness in animal models of colon carcinogenesis
      has not been addressed. Herein, we investigated the in vivo effect of a cocoa
      rich diet in the prevention of azoxymethane (AOM)-induced colon cancer and the
      mechanisms involved. Our results showed that cocoa feeding significantly reduced
      AOM-induced colonic aberrant crypt foci formation and crypt multiplicity.
      Oxidative imbalance in colon tissues seems to be prevented by cocoa as indicated
      by reduced oxidation markers levels and increased enzymatic and non-enzymatic
      endogenous defences. Cocoa-rich diet also exhibited antiproliferative effects by
      decreasing the levels of extracellular regulated kinases, protein kinase B and
      cyclin D1 together with pro-apoptotic effects evidenced by reduced Bcl-x(L) 
      levels and increased Bax levels and caspase-3 activity. Our findings provide the
      first in vivo evidence that a cocoa-rich diet may inhibit the early stage of
      colon carcinogenesis probably by preventing oxidative stress and cell
      proliferation and by inducing apoptosis.

PMID- 21953729
TI  - Analgesic and antiinflammatory activities of taxoids from Taxus wallichiana Zucc.
AB  - A study was conducted to identify constituents that might be responsible for
      analgesic and antiinflammatory conditions. Tasumatrol B, 1,13-diacetyl-10
      deacetylbaccatin III (10-DAD) and 4-deacetylbaccatin III (4-DAB) were isolated
      from the bark extract of Taxus wallichiana Zucc. All the compounds were assessed
      for analgesic and antiinflammatory activities using an acetic acid-induced
      writhing model, a hot-plate test, a carrageenan-induced paw oedema model, a
      cotton-pellet oedema model and in vitro lipoxygenase inhibitory assay. All the
      compounds, especially tasumatrol B, revealed significant analgesic activity in
      comparison to a saline group based on an acetic acid-induced model. Similarly all
      of the test compounds, particularly tasumatrol B, showed significant
      antiinflammatory activity. However, all the compounds failed to exhibit any
      considerable activity in of the hot-plate test and the in vitro lipoxygenase
      inhibitory assay. This study has highlighted the potential of tasumatrol B to be
      further explored as a new lead compound for the management of pain and
      inflammation, one that has been discovered by scientific validation of the
      traditional medicinal use of T. wallichiana Zucc.

PMID- 21953730
TI  - Ex vivo water diffusion tensor properties of the fibroid uterus at 7 T and their
      relation to tissue morphology.
AB  - PURPOSE: To investigate the water diffusion tensor properties of ex vivo tissue
      in the fibroid uterus, including the influence of degeneration, and the relevance
      of the principal eigenvector orientation to the underlying tissue structure.
      MATERIALS AND METHODS: Following hysterectomy, high-resolution structural T(2) 
      weighted and diffusion tensor magnetic resonance imaging (DT-MRI) were performed
      on nine uteri at 7 T. Mean diffusivity (MD), fractional anisotropy (FA), and
      principal eigenvector orientation were measured in myometrium and in myxoid and
      dense tissue in fibroids. Imaging data and measurements of water diffusion
      parameters were compared with histopathology findings. RESULTS: The nine uteri
      yielded 23 fibroids. MD was 50% higher in regions of myxoid degeneration compared
      to dense fibroid tissue (P = 0.001), while myometrium was intermediate in value
      (dense fibroid tissue, P = 0.15; myxoid degeneration, P = 0.23). FA was lower in
      dense fibroid tissue than in myometrium (P = 3 * 10(-5) ), but higher than in
      myxoid tissue (P = 0.003). Principal eigenvector orientation corresponded
      qualitatively with that of uterine smooth muscle fibers. CONCLUSION: The water
      diffusion tensor measured ex vivo in the fibroid uterus is a sensitive probe of
      tissue type, myxoid degeneration, and morphology.

PMID- 21953731
TI  - Aortic valve annulus diameter in Chinese patients with severe calcific aortic
      valve stenosis: implications for transcatheter aortic valve implantation.
AB  - OBJECTIVES: The objective of the study was to describe the distribution and
      determine the predictors of aortic valve annulus diameter (AVAD) in Chinese
      patients with severe calcific aortic valve stenosis (CAS). BACKGROUND: AVAD in
      Chinese patients with CAS has not been reported. Predictors of AVAD in patients
      with CAS are unclear. METHODS: One hundred elderly patients (>=60 years) with
      severe CAS were included in the study. AVAD in all patients was measured by
      transthoracic echocardiograph (AVAD-TTE) and in 74 patients of them was measured
      intra-operatively (AVAD-intra). RESULTS: The intraclass correlation coefficient
      (ICC) between AVAD-TTE and AVAD-intra was 0.81 (95% CI: 0.72-0.88). The
      differences between AVAD-TTE and AVAD-intra ranged from -3 to 3 mm and were <=<=
      2mm in 91.9% (68/74) of patients. The intra-observer ICC for TTE was 0.87 (95%
      CI: 0.74-0.94). Mean AVAD in the whole population was 21.80 +/- 2.09 (17-27) mm.
      11% of cases had an AVAD < 20 mm, 78% had an AVAD between 20 and 24 mm, and 11%
      had an AVAD between 25 and 27 mm. The correlation between AVAD and height (r =
      0.476, P < 0.001) was stronger than that between AVAD and weight (r = 0.215, P =
      0.034) or body surface area (BSA) (r = 0.358, P < 0.001). Multivariate regression
      showed that height, sex, and age but not BSA were independent predictors of AVAD
      (all P < 0.05). CONCLUSION: Most of Chinese patients with CAS can be candidates
      for transcatheter aortic valve implantation procedure in terms of AVAD, whereas
      more sizes of prosthetic valves need to be developed. Sex, age, and especially
      height, but not BAS, are independent predictors of AVAD in patients with CAS.

PMID- 21953732
TI  - Hereditary cancer syndromes: if you look, you will find them.

PMID- 21953733
TI  - Perspective of physicians within a multidisciplinary team: content validation of
      the comprehensive ICF core set for head and neck cancer.
AB  - BACKGROUND: The Comprehensive International Classification of Functioning,
      Disability and Health Core Set for Head and Neck Cancer (ICF-HNC) is an
      application of the ICF and guides multidisciplinary cancer follow-up and
      rehabilitation in patients with head and neck cancer. The objective of this study
      was to understand the role of physicians within the multidisciplinary team and to
      explore the content validity of the ICF-HNC from the perspective of physicians.
      METHODS: In a 3-round Delphi survey, physicians experienced in the treatment of
      head and neck cancer were asked what patients' problems, resources, and aspects
      of environment they treat. The responses of the first round were linked to the
      ICF. In the second round the participants received a list of identified ICF
      categories and were asked if these ICF categories represent patients' problems,
      resources, and aspects of the environment they treat. Round 3 required a
      reconsideration of the given answers in accord with the group response. The
      agreement of the linking process between 2 health care professionals was
      calculated using kappa statistics. RESULTS: In all, 55 physicians from 25
      countries gave 781 statements; 83 ICF categories were linked to the statements
      after the first round; 55 ICF categories reached consensus of >= 75% after the
      third round. Of these, 46 categories (84%) are already included in the ICF-HNC.
      Within the entire ICF-HNC, physicians treat most categories from body structures
      (88%) and functions (76%) and some categories from activities and participation
      (15%) and environmental factors (21%). The kappa coefficient for linking ICF
      categories was 0.988 (95% bootstrapped confidence interval: 0.95-0.99).
      CONCLUSIONS: The content validity of the ICF-HNC was supported by the perspective
      of physicians. This study supports the need for a multidisciplinary team. The
      aspects of functioning which are not treated by physicians should be addressed by
      timely involvement of other health professions.

PMID- 21953734
TI  - Quantifying the effect of urodynamic catheters on urine flow rate measurement.
AB  - INTRODUCTION: The effect of urodynamic catheters on urine flow rate (Q(max) ) is
      well documented but under-researched. Several studies show reduced Q(max) but
      methodologies and patient demographics differ. The aims of this study were to
      further quantify the effect of urodynamic catheters on Q(max) and to explore if
      this was consistent across different urodynamic diagnoses. METHODS: Four groups
      of 50 consecutive men attending for urodynamic studies (UDS) were retrospectively
      analyzed: Group 1 comprised 50 men with normal UDS, Group 2 was 50 men with BOO,
      and Group 3 contained 50 men with detrusor underactivity. Groups 1-3 had UDS
      performed using both 10 Fr filling and 4 Fr measuring catheters in situ. Group 4
      comprised 50 men who had UDS performed with a smaller catheter assembly (8 Fr
      dual-lumen). Values of Q(max) with and without catheters present were compared
      using paired Student's t-tests. Differences between groups were compared using
      ANOVA. RESULTS: Q(max) measured during UDS in men from Groups 1-3 showed a mean
      reduction of 38% compared to Q(max) from "free" uroflowmetry. ANOVA indicated
      this reduction was significantly greater among men with normal UDS. Interestingly
      the group who underwent UDS with a smaller catheter assembly showed no
      significant reduction in Q(max) measured with catheters in situ. CONCLUSION: Our
      findings are in line with previous work suggesting that smaller calibre urethral
      catheters do not cause a significant obstructive effect during voiding. In
      addition it would appear that the reduction in Q(max) with larger urethral
      catheters in situ is greatest in those with normal urodynamics.

PMID- 21953735
TI  - The molecular mechanism of enzymatic glycosyl transfer with retention of
      configuration: evidence for a short-lived oxocarbenium-like species.

PMID- 21953736
TI  - Repeatable procedure for evaluating taper damage on femoral stems with modular
      necks.
AB  - Understanding the performance of dual-taper modular femoral stems necessitates
      detailed quantitative assessment. This study reports a repeatable procedure to
      identify and measure damage on modular taper surfaces and determines whether
      damage area is a useful parameter for discerning modular femoral stem performance
      during in vitro corrosion and endurance tests. Twenty-four dual-taper modular
      necks representing a range of functional conditions were evaluated, including 15
      necks previously subjected to in vitro testing and 9 necks explanted during
      revision hip arthroplasty. Objective identification of six surface features,
      including four unique damage modes, was accomplished using defined criteria
      combined with a standardized photogrammetric method for accurate and repeatable
      measurement of damage area and location. Damage area was a useful parameter for
      discerning the performance of modular femoral stems subjected to different in
      vitro tests. The sum of burnished smooth and textured damage areas was linearly
      correlated with the magnitude of material removed (weight loss) during in vitro
      testing, predicting ~ 1.0 mg additional weight loss for every 10% increase in
      those combined damage areas. Modular necks tested with higher load magnitudes and
      those coupled with larger, stiffer femoral stems were readily distinguished and
      showed significantly larger areas of burnished smooth and textured damage.

PMID- 21953737
TI  - Visual symptoms in Parkinson's disease and Parkinson's disease dementia.
AB  - Visual symptoms are common in PD and PD dementia and include difficulty reading,
      double vision, illusions, feelings of presence and passage, and complex visual
      hallucinations. Despite the established prognostic implications of complex visual
      hallucinations, the interaction between cognitive decline, visual impairment, and
      other visual symptoms remains poorly understood. Our aim was to characterize the
      spectrum of visual symptomatology in PD and examine clinical predictors for their
      occurrence. Sixty-four subjects with PD, 26 with PD dementia, and 32 age-matched
      controls were assessed for visual symptoms, cognitive impairment, and ocular
      pathology. Complex visual hallucinations were common in PD (17%) and PD dementia
      (89%). Dementia subjects reported illusions (65%) and presence (62%) more
      frequently than PD or control subjects, but the frequency of passage
      hallucinations in PD and PD dementia groups was equivalent (48% versus 69%,
      respectively; P = 0.102). Visual acuity and contrast sensitivity was impaired in
      parkinsonian subjects, with disease severity and age emerging as the key
      predictors. Regression analysis identified a variety of factors independently
      predictive of complex visual hallucinations (e.g., dementia, visual acuity, and
      depression), illusions (e.g., excessive daytime somnolence and disease severity),
      and presence (e.g., rapid eye movement sleep behavior disorder and excessive
      daytime somnolence). Our results demonstrate that different "hallucinatory"
      experiences in PD do not necessarily share common disease predictors and may,
      therefore, be driven by different pathophysiological mechanisms. If confirmed,
      such a finding will have important implications for future studies of visual
      symptoms and cognitive decline in PD and PD dementia.

PMID- 21953738
TI  - An additional dehydratase-like activity is required for lankacidin antibiotic
      biosynthesis.

PMID- 21953739
TI  - Effects of a randomised reading intervention study: an application of structural
      equation modelling.
AB  - An intensive phonics-based intervention program for nine-year-old Swedish pupils
      with reading difficulties was performed. Pupils (N = 112) were randomly assigned
      to either an intervention or a control group. The training was tailored to the
      Swedish transparent orthography and designed for one-to-one-tutoring during
      twelve weeks. Previously, reading speed has been shown to be hard to remediate,
      and one important purpose was to improve reading speed by explicit training. The
      intervention group showed improvements immediately after intervention in
      spelling, reading comprehension, reading speed, and phoneme awareness. There were
      also significant indirect effects from intervention to all variables one year
      later. Reading comprehension at immediate post-test predicted spelling one year
      later, and phoneme awareness at post-test predicted both spelling and reading
      comprehension one year later. The results suggest the importance of a multi
      component intervention, even in transparent orthographies, which includes phonics
      combined with comprehension strategies and fluency training.

PMID- 21953741
TI  - Logistic regression analysis of biomarker data subject to pooling and
      dichotomization.
AB  - There is growing interest in pooling specimens across subjects in epidemiologic
      studies, especially those involving biomarkers. This paper is concerned with
      regression analysis of epidemiologic data where a binary exposure is subject to
      pooling and the pooled measurement is dichotomized to indicate either that no
      subjects in the pool are exposed or that some are exposed, without revealing
      further information about the exposed subjects in the latter case. The pooling
      process may be stratified on the disease status (a binary outcome) and possibly
      other variables but is otherwise assumed random. We propose methods for
      estimating parameters in a prospective logistic regression model and illustrate
      these with data from a population-based case-control study of colorectal cancer.
      Simulation results show that the proposed methods perform reasonably well in
      realistic settings and that pooling can lead to sizable gains in cost efficiency.
      We make recommendations with regard to the choice of design for pooled
      epidemiologic studies.

PMID- 21953740
TI  - Alkaloid Profiling as an Approach to Differentiate Lupinus garfieldensis, Lupinus
      sabinianus and Lupinus sericeus.
AB  - INTRODUCTION: Many species in the Lupinus genus are poorly defined
      morphologically, potentially resulting in improper taxonomic identification.
      Lupine species may contain quinolizidine and/or piperidine alkaloids that can be
      acutely toxic and/or teratogenic, the latter resulting in crooked calf disease.
      OBJECTIVE: To identify characteristic alkaloid profiles of Lupinus sabinianus, L.
      garfieldensis and L. sericeus which would aid in discriminating these species
      from each other and from L. sulphureus. METHODS AND MATERIALS: Quinolizidine and
      piperidine alkaloids were extracted from herbarium specimens and recent field
      collections of L. sabinianus, L. garfieldensis and L. sericeus. The alkaloid
      composition of each species was defined using GC-FID and GC-MS and compared using
      multivariate statistics. RESULTS: Each of the three species investigated
      contained a diagnostic chemical fingerprint composed of quinolizidine and/or
      piperidine alkaloids. CONCLUSION: The alkaloid profiles of Lupinus sabinianus, L.
      garfieldensis and L. sericeus can be used as a tool to discriminate these species
      from each other and L. sulphureus as long as one considers locality of the
      collection in the case of L. sabinianus.

PMID- 21953742
TI  - Regio- and chemoselective metalation of arenes and heteroarenes using hindered
      metal amide bases.
AB  - The preparation of highly functionalized organometallic compounds can be achieved
      by direct C-H activation of a broad range of unsaturated substrates using lithium
      chloride solubilized 2,2,6,6-tetramethylpiperidide bases (TMP(n)MX(m)?p LiCl).
      These are excellent reagents for converting a wide range of aromatic and
      heterocyclic substrates into valuable organometallic reagents with broad
      applications in organic synthesis.

PMID- 21953744
TI  - Validation of a radioimmunoassay for measuring testosterone concentrations in
      plasma samples of the subterranean rodent Ctenomys talarum: outstandingly
      elevated levels in the wild and the effect of captivity.
AB  - We validated the Coat-a-Count radioimmunoassay (RIA) kit for measuring
      testosterone in plasma samples of the subterranean rodent Ctenomys talarum and
      evaluated testosterone levels in free-living and captive individuals. The
      performance of the assay was evaluated by the assessment of parallelism, accuracy
      and precision. Moreover, the high specificity of the assay antibody was confirmed
      by high-pressure liquid chromatography with ultraviolet detector, followed by
      electrospray ionization tandem mass spectrometry. Results indicated that plasma
      samples have to be treated with heat and diluted before the RIA for the
      optimization of the assay. Plasma testosterone concentrations in free-living
      animals were outstandingly elevated (up to 329 ng/mL), which are among the
      highest ever reported for mammals. On the other hand, captivity produced a 14
      fold decrease in plasma testosterone concentrations, emphasizing that very
      significant changes in the endocrine milieu may occur in wild animals kept under
      laboratory conditions. Our results place tuco-tucos as an interesting model for
      the study of androgen regulation in mammals, suggesting that target tissues may
      have low sensitivity to the testosterone signal and agree with a scenario of
      elevated levels of sex hormone-binding globulin in plasma.

PMID- 21953745
TI  - Recognition and uptake of free and nanoparticle-bound betalactoglobulin--a food
      allergen--by human monocytes.
AB  - SCOPE: To improve our understanding of the interaction of food allergens with
      cells of the immune system, the endocytosis by human monocytes of bovine beta
      lactoglobulin (BLG) and ovomucoid (OM)--two major food allergens--and human serum
      albumin (HSA) was studied. METHODS AND RESULTS: BLG was covalently conjugated to
      dextran-coated magnetic nanoparticles (MNPs) without affecting its structure and
      immunoreactivity. BLG-conjugated MNPs were taken up by human monocytes much more
      efficiently than non-conjugated MNPs, allowing easy magnetic separation of cells
      that had adsorbed the allergen. BLG, OM, and HSA were conjugated to MNPs also
      labeled with a fluorescent probe. The uptake of these materials by human
      monocytes was monitored through flow cytometry, and compared with fluorescent
      MNPs and the free fluorescently labeled proteins, confirming higher uptake of the
      BLG-conjugated MNPs versus non-conjugated MNPs. OM but not HSA conjugation to
      particles enhanced uptake of the MNPs. Confocal microscopy provided direct
      evidence of the actual internalization of BLG-MNP conjugates into the cytoplasm.
      CONCLUSIONS: These results contribute to the current understanding of the
      interaction between food allergens and antigen-presenting cells, and demonstrate
      that the BLG is readily endocytosed by monocytes both as the single protein and
      as a conjugate.

PMID- 21953746
TI  - Emeraldicene as an acceptor moiety: balanced-mobility, ambipolar, organic thin
      film transistors.

PMID- 21953747
TI  - The fine balance of quality and quantity: the time has come to define quality of
      PCI!

PMID- 21953743
TI  - RNAi screening: new approaches, understandings, and organisms.
AB  - RNA interference (RNAi) leads to sequence-specific knockdown of gene function.
      The approach can be used in large-scale screens to interrogate function in
      various model organisms and an increasing number of other species. Genome-scale
      RNAi screens are routinely performed in cultured or primary cells or in vivo in
      organisms such as C. elegans. High-throughput RNAi screening is benefitting from
      the development of sophisticated new instrumentation and software tools for
      collecting and analyzing data, including high-content image data. The results of
      large-scale RNAi screens have already proved useful, leading to new
      understandings of gene function relevant to topics such as infection, cancer,
      obesity, and aging. Nevertheless, important caveats apply and should be taken
      into consideration when developing or interpreting RNAi screens. Some level of
      false discovery is inherent to high-throughput approaches and specific to RNAi
      screens, false discovery due to off-target effects (OTEs) of RNAi reagents
      remains a problem. The need to improve our ability to use RNAi to elucidate gene
      function at large scale and in additional systems continues to be addressed
      through improved RNAi library design, development of innovative computational and
      analysis tools and other approaches.

PMID- 21953748
TI  - Cardiogenic shock complicating acute myocardial infarction in the elderly:
      predictors of long-term survival.
AB  - BACKGROUND: Cardiogenic shock (CS) is a severe complication of acute myocardial
      infarction (AMI), associated with a high mortality. A significant improvement in
      survival has been reported with immediate coronary revascularization. However,
      there is no clear evidence of such an improvement amongst older patients. The aim
      of our work was to evaluate in-hospital and long-term outcomes in the group of
      elderly AMI patients with CS (>=75 years old). METHODS: We collected data of 157
      consecutive AMI patients with CS who underwent percutaneous coronary intervention
      (PCI) and compared clinical and procedural characteristics and in-hospital and
      long-term outcomes between patients <75 years and patients >=75 years old.
      RESULTS: There were 58 patients (36.9%) with age >=75 years and 99 patients
      (63.1%) with age <75 years. Patients were followed up for an average period of 34
      months (range 5-69). In-hospital and long-term mortality was significantly higher
      in the older group (55 vs. 25%, P < 0.0001; and 62.1 vs. 37.3%, P = 0.005,
      respectively). Multivariate predictors of in-hospital mortality were age >=75
      years (hazard ratio 1.81, 95% CI 1.006-3.27, P = 0.04) and PCI failure (hazard
      ratio 2.67, 95% CI 1.34-5.307, P = 0.005), whereas, the only multivariate
      predictor of long-term mortality was PCI failure (hazard ratio 2.88, 95% CI 1.52
      5.46, P = 0.001). Age >=75 years showed only a trend toward statistical
      significance (hazard ratio 1.62, 95% CI 0.96-2.76, P = 0.07). CONCLUSIONS: In
      elderly AMI patients with CS, PCI can be performed with an acceptable risk that
      seems lower than that reported in most previous studies.

PMID- 21953749
TI  - Shock and age: the role of an early invasive strategy.

PMID- 21953750
TI  - The ACSIS Registry and primary angioplasty following coronary bypass surgery.

PMID- 21953751
TI  - The revascularization paradox rules.

PMID- 21953752
TI  - Confined distally: a novel method for retrieving a trapped burr.

PMID- 21953753
TI  - Getting out of jail: creative solutions in a moment of crisis.

PMID- 21953754
TI  - No news is good news, but....

PMID- 21953755
TI  - The flow from below.

PMID- 21953756
TI  - In-stent restenosis: while not exactly about smoking, it so often is about
      smoking.

PMID- 21953757
TI  - Timing of nitinol stent restenosis in superficial artery disease: one year is
      good enough?

PMID- 21953758
TI  - Radial perforation: after the routine has failed.

PMID- 21953759
TI  - Fate of mitral regurgitation following transcatheter aortic valve implantation:
      the achilles heel of core valve?

PMID- 21953760
TI  - Left main occlusion with transcatheter aortic valve replacement.

PMID- 21953762
TI  - Enantiomers of naringenin as pleiotropic, stereoselective inhibitors of
      cytochrome P450 isoforms.
AB  - Interactions between naringenin and the cytochrome P450 (CYP) system have been of
      interest since the first demonstration that grapefruit juice reduced CYP3A
      activity. The effects of naringenin on other CYP isoforms have been less
      investigated. In addition, it is well known that interactions with enzymes are
      often stereospecific, but due to the lack of readily available pure naringenin
      enantiomers, the enantioselectivity of its effects has not been characterized. We
      isolated pure naringenin enantiomers by chiral high-performance liquid
      chromatography and tested the ability of (R)-,(S)- and rac-naringenin to inhibit
      several important drug-metabolizing CYP isoforms using recombinant enzymes and
      pooled human liver microsomes. Naringenin was able to inhibit CYP19, CYP2C9, and
      CYP2C19 with IC50 values below 5 MUM. No appreciable inhibition of CYP2B6 or
      CYP2D6 was observed at concentrations up to 10 MUM. Whereas (S)-naringenin was 2
      fold more potent as an inhibitor of CYP19 and CYP2C19 than (R)-naringenin, (R)
      naringenin was 2-fold more potent for CYP2C9 and CYP3A. Chiral flavanones like
      naringenin are difficult to separate into their enantiomeric forms, but
      enantioselective effects may be observed that ultimately impact clinical effects.
      Inhibition of specific drug metabolizing enzymes by naringenin observed in vitro
      may be exploited to understand pharmacokinetic changes seen in vivo.

PMID- 21953763
TI  - Opioid patient controlled analgesia use during the initial experience with the
      IMPROVE PCA trial: a phase III analgesic trial for hospitalized sickle cell
      patients with painful episodes.
AB  - Opioid analgesics administered by patient-controlled analgesia (PCA)are
      frequently used for pain relief in children and adults with sickle cell disease
      (SCD) hospitalized for persistent vaso-occlusive pain, but optimum opioid dosing
      is not known. To better define PCA dosing recommendations,a multi-center phase
      III clinical trial was conducted comparing two alternative opioid PCA dosing
      strategies (HDLI-higher demand dose with low constant infusion or LDHI-lower
      demand dose and higher constant infusion) in 38 subjects who completed
      randomization prior to trial closure. Total opioid utilization (morphine
      equivalents,mg/kg) in 22 adults was 11.6 +/- 2.6 and 4.7 +/- 0.9 in the HDLI
      andin the LDHI arms, respectively, and in 12 children it was 3.7 +/- 1.0 and 5.8
      +/- 2.2, respectively. Opioid-related symptoms were mild and similar in both PCA
      arms (mean daily opioid symptom intensity score: HDLI0.9 +/- 0.1, LDHI 0.9 +/-
      0.2). The slow enrollment and early study termination limited conclusions
      regarding superiority of either treatment regimen. This study adds to our
      understanding of opioid PCA usage in SCD. Future clinical trial protocol designs
      for opioid PCA may need to consider potential differences between adults and
      children in PCA usage.

PMID- 21953761
TI  - A human monoclonal antibody targeting scavenger receptor class B type I precludes
      hepatitis C virus infection and viral spread in vitro and in vivo.
AB  - Endstage liver disease caused by chronic hepatitis C virus (HCV) infection is the
      leading indication for liver transplantation in the Western world. However,
      immediate reinfection of the grafted donor liver by circulating virus is
      inevitable and liver disease progresses much faster than the original disease.
      Standard antiviral therapy is not well tolerated and usually ineffective in liver
      transplant patients, whereas anti-HCV immunotherapy is hampered by the extreme
      genetic diversity of the virus and its ability to spread by way of cell-cell
      contacts. We generated a human monoclonal antibody against scavenger receptor
      class B type I (SR-BI), monoclonal antibody (mAb)16-71, which can efficiently
      prevent infection of Huh-7.5 hepatoma cells and primary hepatocytes by cell
      culture-derived HCV (HCVcc). Using an Huh7.5 coculture system we demonstrated
      that mAb16-71 interferes with direct cell-to-cell transmission of HCV. Finally we
      evaluated the in vivo efficacy of mAb16-71 in "human liver urokinase-type
      plasminogen activator, severe combined immune deficiency (uPA-SCID) mice"
      (chimeric mice). A 2-week anti-SR-BI therapy that was initiated 1 day before
      viral inoculation completely protected all chimeric mice from infection with
      serum-derived HCV of different genotypes. Moreover, a 9-day postexposure therapy
      that was initiated 3 days after viral inoculation (when viremia was already
      observed in the animals) suppressed the rapid viral spread observed in untreated
      control animals. After cessation of anti-SR-BI-specific antibody therapy, a rise
      of the viral load was observed. CONCLUSION: Using in vitro cell culture and human
      liver-chimeric mouse models, we show that a human mAb targeting the HCV
      coreceptor SR-BI completely prevents infection and intrahepatic spread of
      multiple HCV genotypes. This strategy may be an efficacious way to prevent
      infection of allografts following liver transplantation in chronic HCV patients,
      and may even hold promise for the prevention of virus rebound during or following
      antiviral therapy.

PMID- 21953764
TI  - Berberine inhibits pulmonary metastasis through down-regulation of MMP in
      metastatic B16F-10 melanoma cells.
AB  - The present study demonstrated the potential antimetastatic and antiinvasive
      effect of berberine using both in vivo mouse lung metastasis and in vitro models.
      Administration of berberine resulted in significant suppression of B16F-10
      melanoma induced tumor nodule formation and enhanced the survival of tumor
      bearing mice. Berberine treatment also decreased various biochemical parameters
      associated with lung metastasis. These inhibitory actions may be due to the
      significant suppression of several signaling molecules such as ERK1/2, NF-kappaB,
      ATF-2 and CREB involved in the transcription signaling pathways for MMP gene
      expression. It could also inhibit the migration and invasion of highly metastatic
      murine melanoma cells in a dose-dependent manner in vitro. The results clearly
      show that berberine could significantly inhibit experimental lung metastasis
      produced by intravenous injection of B16F-10 melanoma cells and this effect could
      be linked to the down-regulation of metastasis-related signaling molecules.

PMID- 21953765
TI  - Barriers to and facilitators for the use of an evidence-based occupational
      therapy guideline for older people with dementia and their carers.
AB  - OBJECTIVE: Implementing evidence-based guidelines is not a simple task. This
      study aimed to define barriers to and facilitators for implementing the proven
      and effective Community Occupational Therapy in Dementia (COTiD) guideline for
      older people with dementia and their carers. METHODS: The qualitative method we
      used was the grounded theory. We collected data from focus group interviews with
      17 occupational therapists (OTs) and telephone interviews with 10 physicians and
      4 managers. We analysed the data with the constant comparative method by
      identifying codes, categories, and main themes. RESULTS: The main themes in
      barriers that OTs encountered were that they did not feel competent in treating
      older people with dementia at home according to the guideline; they had
      difficulties prioritising in this complex treatment, both for the client and
      themselves; and they were unsure about the minimal criteria for guideline
      adherence. The intensity of this programme was the main barrier. The barriers
      that confronted physicians and managers were lack of knowledge about occupational
      therapy and its reimbursement and lack of available trained OTs. For the OTs, the
      guideline's content and focus, evidence, and external support facilitated the use
      of the guideline. For physicians and managers, the guideline's evidence base and
      its benefits for clients and carers were the main facilitators. CONCLUSIONS: This
      study generates knowledge for applying innovations in health care settings.
      Improvement of the OTs' knowledge and self-confidence is needed for using the
      guideline. We expect that more competent OTs will motivate their physicians and
      managers to use this successful COTiD intervention.

PMID- 21953766
TI  - Long-term clinical outcomes in patients treated with drug-eluting compared to
      bare-metal stents for the treatment of transplant coronary artery disease.
AB  - OBJECTIVE: We aimed to compare the long-term clinical outcomes of first-vessel
      percutaneous coronary intervention (PCI) with drug-eluting stents (DES) and bare
      metal stents (BMS) for the treatment of transplant coronary artery disease
      (TCAD). BACKGROUND: TCAD is the leading cause of late death in orthotopic heart
      transplantation (OHT) recipients. PCI is associated with worse clinical outcomes
      compared with non-OHT patients. Our institution previously reported superior
      angiographic outcomes with DES compared with BMS in OHT patients. However, long
      term clinical outcomes comparing PCI with DES versus BMS are lacking. METHODS:
      The data on 105 OHT recipients who underwent first-vessel PCI with DES (n = 58)
      or BMS (n = 47) at UCLA Medical Center between 1995 and 2009 were retrospectively
      analyzed. RESULTS: Five-year clinical outcomes were not significantly different
      with DES and BMS in terms of the composite of death, myocardial infarction (MI),
      or target vessel revascularization (TVR) [(40.8 +/- 7.2)% vs. (59.6 +/- 7.2)%,
      log-rank P = 0.33], death [(31.8 +/- 7.8)% vs. (40.4 +/- 7.2)%, log-rank P =
      0.46], MI [(12.2 +/- 6.2)% vs. (11.3 +/- 5.4)%, log rank P = 0.98], TVR [(25.5 +/
      6.9)% vs. (26.5 +/- 7.3)%, log rank P = 0.76], and time to repeat OHT [(2.27 +/-
      1.79) vs. (3.22 +/- 3.34), P = 0.98]. CONCLUSIONS: At long-term follow-up, PCI
      with DES and BMS provided similar clinical outcomes in OHT. Long-term mortality
      remains high in OHT recipients after PCI with either DES or BMS. Randomized
      clinical trials are required to determine the optimal treatment strategy for OHT
      recipients with TCAD.

PMID- 21953767
TI  - Congenital pancreatoblastoma associated with beta-catenin mutation.

PMID- 21953768
TI  - Carbon dioxide carbonates in the earth's mantle: implications to the deep carbon
      cycle.

PMID- 21953769
TI  - Increased bladder activity is associated with elevated oxidative stress markers
      and proinflammatory cytokines in a rat model of atherosclerosis-induced chronic
      bladder ischemia.
AB  - AIMS: To further characterize, in a rat model, the effects of atherosclerosis
      induced chronic bladder ischemia on bladder function and associated changes in
      oxidative stress markers and proinflammatory cytokines. METHODS: Adult Sprague
      Dawley male rats were divided into three groups (arterial endothelial injury: AI,
      sham, naive). The AI group (n = 14) underwent endothelial injury of the iliac
      arteries and received a 2% cholesterol diet. The sham group (n = 12) underwent
      sham operation and received a 2% cholesterol diet. The naive group (n = 12)
      received a regular diet. After 8 weeks, cystometrograms (CMG) without anesthesia
      or restraint were performed. In bladders from each group, oxidative stress
      markers (8-hydroxy-2'-deoxyguanosine: 8-OHdG; malondialdehyde: MDA) and
      proinflammatory cytokines (IL-8 like cytokine CXCL1/CINC-1, TNF-alpha, IL-6) were
      quantified. Histological examination of the iliac arteries was also performed.
      RESULTS: At 8 weeks, the body and bladder wet weights were not significant
      different among the three groups. The micturition interval in the AI group
      decreased significantly compared with those in the other two groups, but maximum
      pressure during micturition did not change. The iliac arteries in the AI group
      revealed thickening of intima as well as diffuse media fibrosis at the sites of
      balloon injury. The levels of oxidative stress markers and proinflammatory
      cytokines were significantly higher in the AI than in the other groups.
      CONCLUSION: Oxidative stress and inflammation may be key factors in the
      development of bladder overactivity in atherosclerosis-induced chronic bladder
      ischemia.

PMID- 21953770
TI  - Globus pallidus internus-deep brain stimulation in Tourette's syndrome: can
      clinical symptoms predict response?

PMID- 21953771
TI  - In vivo tibiofemoral cartilage-to-cartilage contact area of females with medial
      osteoarthritis under acute loading using MRI.
AB  - PURPOSE: To investigate the effect of acute loading on in vivo tibiofemoral
      contact area changes in both compartments, and to determine whether in vivo
      tibiofemoral contact area differs between subjects with medial knee
      osteoarthritis (OA) and healthy controls. MATERIALS AND METHODS: Ten subjects
      with medial knee OA (KL3) and 11 control subjects (KL0) were tested. Coronal
      three-dimensional spoiled gradient-recalled (3D-SPGR) and T(2) -weighted fast
      spin-echo FSE magnetic resonance imaging (MRI) of the knee were acquired under
      both unloaded and loaded conditions. Tibiofemoral cartilage contact areas were
      measured using image-based 3D models. RESULTS: Tibiofemoral contact areas in both
      compartments significantly increased under loading (P < 0.001) and the increased
      contact area in the medial compartment was significantly larger than in the
      lateral compartment (P < 0.05). Medial compartment contact area was significantly
      larger in KL3 subjects than KL0 subjects, both at unloaded and loaded conditions
      (P < 0.05). Contact areas measured from 3D-SPGR and T(2) -weighted FSE images
      were strongly correlated (r = 0.904). CONCLUSION: Females with medial OA
      increased tibiofemoral contact area in the medial compartment compared to healthy
      subjects under both unloaded and loaded conditions. The contact area data
      presented in this study may provide a quantitative reference for further
      cartilage contact biomechanics such as contact stress analysis and cartilage
      biomechanical function difference between osteoarthritic and healthy knees.

PMID- 21953772
TI  - Porous poly(D,L-lactic acid) foams with tunable structure and mechanical
      anisotropy prepared by supercritical carbon dioxide.
AB  - The design and tunability of tissue scaffolds, such as pore size and geometry, is
      crucial to the success of an engineered tissue replacement. Moreover, the
      mechanical nature of a tissue scaffold should display properties similar to the
      tissue of interest; therefore, tunability of the foam mechanical properties is
      desirable. Polymeric foams prepared using supercritical carbon dioxide as a
      blowing agent has emerged in recent years as a promising technique to prepare
      porous scaffolds. While a number of groups have reported on the tailoring of
      scaffold morphologies by using gas foaming techniques, few have considered the
      effects of such processing conditions on the physical and mechanical anisotropy
      achieved. The aim of this study was to demonstrate the tunability of the
      structure and mechanical anisotropy of foams prepared using a variety of
      different gas foaming conditions. Porous poly(D,L lactic acid) foams were
      prepared by the systematic adjustment of processing conditions, namely pressure,
      temperature and venting time, resulting in an extensive range of scaffold
      morphologies. Characterization of sample anisotropy was achieved by mechanical
      evaluation of foam specimens both longitudinal and transverse to the foaming
      direction. The obtained mechanical properties demonstrated a strong dependence of
      the processing conditions on mechanical anisotropy and performance. Furthermore,
      results indicate that factors other than pore geometry may be necessary to define
      the mechanical behavior of the foam specimens. The favorable compressive moduli,
      coupled with large degrees of anisotropy, suggests these foams may have suitable
      application as scaffolds for bone tissue engineering.

PMID- 21953773
TI  - Risks and clinical implications of perineural invasion in T1-2 oral tongue
      squamous cell carcinoma.
AB  - BACKGROUND: Risks of perineural invasion (PNI) in T1-2 oral tongue squamous cell
      carcinoma (SCC) have not been specifically elucidated. METHODS: Pathological
      features, including PNI, were re-reviewed under regular hematoxylin-eosin
      staining in 190 patients with T1-2 oral tongue SCC. RESULTS: Tumor thickness >5
      mm, PNI(+), and lymphovascular invasion (+) independently predicted lymph node
      involvement. PNI(+) and neck observation also independently predicted neck
      recurrence, but only PNI(+) was associated with a poor disease-specific survival
      (DSS; p = .003). In patients who were clinically node negative (cN0), elective
      neck dissection contributed to a better DSS in patients with PNI(+) tumors (p =
      .046), but not in patients with PNI (-) tumors (p = .809). Additionally,
      increased tumor thickness predicted the presence of PNI. CONCLUSION: PNI is a
      crucial pathological feature for T1-2 oral tongue SCC. Elective neck dissection
      should be performed in patients who were cN0 with PNI. Careful evaluation for PNI
      should be advocated in regular pathological diagnosis.

PMID- 21953774
TI  - Facile preparation of high-quality graphene scrolls from graphite oxide by a
      microexplosion method.

PMID- 21953775
TI  - Triggering dissymmetry in achiral dye molecules by chiral solvents: Circular
      dichroism experiments and DFT calculations.
AB  - The electronic circular dichroism spectra of achiral product "Lumogen F Red" (ROT
      300) in four different chiral solvents are recorded at different temperatures.
      DFT calculations allow to identify two enantiomeric conformers for ROT-300. In
      vacuo they are equally populated; in chiral solvents one enantiomer prevails.
      Thermodynamic quantities involved in the chiral preference are derived.

PMID- 21953776
TI  - The binding mode of cladocoran A to the human group IIA phospholipase A(2).
AB  - The molecular basis for human group IIA phospholipase A(2)  inactivation by the
      marine natural product cladocoran A (CLD A) has been studied in order to
      elucidate its relevant anti-inflammatory properties. Indeed, secretory
      phospholipases A(2)  are well-known to be implicated in the pathogenesis of
      inflammation, such as rheumatoid arthritis, septic shock, psoriasis and asthma,
      thus the understanding of their inactivation mechanism could be useful for the
      development of new chemical classes of selective inhibitors. Our results,
      collected by a combination of biochemical approaches, advanced mass spectrometry
      and molecular modeling, suggest a competitive inhibition mechanism guided by a
      noncovalent molecular recognition event, and disclose the key role of the CLD A
      gamma-hydroxybutenolide ring in the chelation of the catalytic calcium ion inside
      the enzyme active site. Moreover, CLD A is able to react selectively with Ser82,
      although this covalent event seems to play a secondary role in terms of enzyme
      inhibition.

PMID- 21953778
TI  - Cold-blooded snipers: thermal independence of ballistic tongue projection in the
      salamander Hydromantes platycephalus.
AB  - Plethodontid salamanders of the genus Hydromantes capture prey using the most
      extreme tongue projection among salamanders, and can shoot the tongue a distance
      of 80% of body length in less than 20 msec. The tongue skeleton is projected from
      the body via an elastic-recoil mechanism that decouples muscle contraction from
      tongue projection, amplifying muscle power tenfold. We tested the hypothesis that
      the elastic-recoil mechanism also endows tongue projection with low thermal
      dependence by examining the kinematics and dynamics of tongue projection in
      Hydromantes platycephalus over a range of body temperatures (2-24 degrees C). We
      found that H. platycephalus maintained tongue-projection performance over the
      tested temperature range and that tongue projection showed thermal independence
      (Q(10) values of 0.94-1.04) of all performance parameters including projection
      distance, average velocity, and peak instantaneous values of velocity,
      acceleration, and power. Nonelastic, muscle-powered tongue retraction, in
      contrast, responded to temperature changes significantly differently than elastic
      tongue projection; performance parameters of retraction displayed thermal
      dependence typical of muscle-powered movement (Q(10) values of 1.63-4.97). These
      results reveal that the elastic-recoil mechanism liberates tongue projection from
      the effects of temperature on muscle contractile rates. We suggest that relative
      thermal independence is a general characteristic of elastic-recoil mechanisms and
      may promote the evolution of these mechanisms in ectothermic animals.

PMID- 21953780
TI  - Letter on Shahidi et al. (2011): "Laughter Yoga versus group exercise program in
      elderly depressed women: a randomized controlled trial" I -- first things first!
      Caveats in research on "laughter yoga".

PMID- 21953779
TI  - Successful isolation of liver progenitor cells by aldehyde dehydrogenase activity
      in naive mice.
AB  - The role of progenitor cells in liver repair and fibrosis has been extensively
      described, but their purification remains a challenge, hampering their
      characterization and use in regenerative medicine. To address this issue, we
      developed an easy and reproducible liver progenitor cell (LPC) isolation strategy
      based on aldehyde dehydrogenase (ALDH) activity, a common feature shared by many
      progenitor cells. We demonstrate that a subset of nonparenchymal mouse liver
      cells displays high levels of ALDH activity, allowing the isolation of these
      cells by fluorescence-activated cell sorting. Immunocytochemistry and qPCR
      analyses on freshly isolated ALDH(+) cells reveal an enrichment in cells
      expressing liver stem cell markers such as EpCAM, CK19, CD133, and Sox9. In
      culture, the ALDH(+) population can give rise to functional hepatocyte-like cells
      as illustrated by albumin and urea secretion and cytochrome P450 activity.
      ALDH1A1 expression can be detected in canals of Hering and bile duct epithelial
      cells and is increased on liver injury. Finally, we showed that the isolation and
      differentiation toward hepatocyte-like cells of LPCs with high ALDH activity is
      also successfully applicable to human liver samples. CONCLUSION: High ALDH
      activity is a feature of LPCs that can be taken advantage of to isolate these
      cells from untreated mouse as well as human liver tissues. This novel protocol is
      practically relevant, because it provides an easy and nontoxic method to isolate
      liver stem cells from normal tissue for potential therapeutic purposes.

PMID- 21953781
TI  - Cognitive profiles of Korean poor readers.
AB  - This study compared the performance of 30 poor readers in the third grade with
      those of 30 average readers of the same age and 30 younger readers matched with
      the same reading level on phonological, visuo-perceptual, orthographic, and
      naming speed tasks. Individual data revealed heterogeneous profiles for the poor
      readers: six (20%) exhibited visual deficit; two (6.7%) had a single phonological
      deficit; and six (20%) had a double phonological and visual deficit. A naming
      speed deficit appeared, not as a single type, but in association with a
      phonological deficit (23.3%), a visual deficit (3.3%), or both (10%). These
      results suggest that Koreans' most significant reading problems lie in
      phonological awareness and in visual and naming speed processing. In particular,
      phonological and visual deficits are major independent risk factors in Korean
      reading impairments.

PMID- 21953782
TI  - Fluorine conformational effects in organocatalysis: an emerging strategy for
      molecular design.
AB  - Molecular design strategies that profit from the intrinsic stereoelectronic and
      electrostatic effects of fluorinated organic molecules have mainly been
      restricted to bio-organic chemistry. Indeed, many fluorine conformational effects
      remain academic curiosities with no immediate application. However, the
      renaissance of organocatalysis offers the possibility to exploit many of these
      well-described phenomena for molecular preorganization. In this minireview, we
      highlight examples of catalyst refinement by introduction of an aliphatic C-F
      bond which functions as a chemically inert steering group for conformational
      control.

PMID- 21953783
TI  - Screening and determination for potential alpha-glucosidase inhibitors from
      leaves of Acanthopanax senticosus harms by using UF-LC/MS and ESI-MS(n).
AB  - INTRODUCTION: Acanthopanax senticosus Harms is a typical Chinese herb with
      flavonoids existing in all parts of the plant but with the largest content in
      leaves. However, leaves have been neglected in past research. To investigate the
      potential use of leaves of A. senticosus Harms for discovering lead compounds to
      treat type 2 diabetes, the herb leaves were selected for screening the potential
      of alpha-glucosidase inhibitors. OBJECTIVE: To screen for candidates of alpha
      glucosidase inhibitors from leaves of A. senticosus Harms and evaluate the
      structure-activity relationship of the alpha-glucosidase inhibitors. METHODOLOGY:
      Ultrafiltration liquid chromatography/mass spectrometry (UF-LC/MS) assay was
      developed for screening candidates of alpha-glucosidase inhibitors from leaves of
      A. senticosus Harms. The interesting compounds were identified by using reversed
      phase high performance liquid chromatography with diode array detector and
      electrospray ionisation multiple-stage tandem mass spectrometry (RP-HPLC-DAD-ESI
      MS(n) ), and confirmed by using electrospray ionisation Fourier transform ion
      cyclotron resonance multiple-stage tandem mass spectrometry (ESI-FT-ICR-MS(n)).
      Furthermore, the alpha-glucosidase inhibitory activity of the compounds detected
      was estimated using in vitro assays. RESULTS: Eight compounds that might bind to
      alpha-glucosidase were screened and seven of them were identified successfully.
      The alpha-glucosidase inhibitory activity of the related compounds in leaves of
      A. senticosus Harms was determined. CONCLUSION: The results obtained provided new
      information for the discovery of potential alpha-glucosidase inhibitors and the
      potential anti-diabetic application of the leaves of A. senticosus Harms.

PMID- 21953785
TI  - Resizing metal-coated nanopores using a scanning electron microscope.
AB  - Electron beam-induced shrinkage provides a convenient way of resizing solid-state
      nanopores in Si(3) N(4) membranes. Here, a scanning electron microscope (SEM) has
      been used to resize a range of different focussed ion beam-milled nanopores in Al
      coated Si(3) N(4) membranes. Energy-dispersive X-ray spectra and SEM images
      acquired during resizing highlight that a time-variant carbon deposition process
      is the dominant mechanism of pore shrinkage, although granular structures on the
      membrane surface in the vicinity of the pores suggest that competing processes
      may occur. Shrinkage is observed on the Al side of the pore as well as on the
      Si(3) N(4) side, while the shrinkage rate is observed to be dependent on a
      variety of factors.

PMID- 21953786
TI  - Targeted delivery of polyoxometalate nanocomposites.
AB  - Polyoxometalate/carboxymethyl chitosan nanocomposites with an average diameter of
      130 nm are synthesized and labeled with fluorescein isothiocyanate (FITC) for a
      combined drug-carrier and cellular-monitoring approach. [Eu(beta(2) -SiW(11)
      O(39) )(2) ](13-) /CMC nanospheres as a representative example do not display
      cytotoxicity for POM concentrations up to 2 mg mL(-1) . Cellular uptake of
      fluoresecently labelled {EuSiW(11) O(39) }/FITC-CMC nanoparticles is monitored
      with confocal laser scanning microscopy. Nanoparticle uptake occurs after
      incubation times of around 1 h and no cyctotoxic effects are observed upon
      prolonged treatment. The preferential location of the POM/CMC nanocomposites in
      the perinuclear region is furthermore verified with transmission electron
      microscopy investigations on unlabeled nanoparticles. Therefore, this approach is
      a promising dual strategy for the safe cellular transfer and monitoring of
      bioactive POMs.

PMID- 21953787
TI  - The role of embolic protection devices during carotid stenting prior to cardiac
      surgery in asymptomatic patients: empty filters?
AB  - OBJECTIVES: The purpose of this study was to analyze the debris captured in the
      distal protection filters used during carotid artery stenting (CAS). BACKGROUND:
      CAS is an option available to high-risk patients requiring revascularization.
      Filters are suggested for optimal stroke prevention during CAS. METHODS: From May
      2005 to June 2007, filters from 59 asymptomatic patients who underwent CAS were
      collected and sent to a specialized laboratory for light-microscope and
      histological analysis. Peri- and postprocedural outcomes were assessed during 1
      year follow-up. RESULTS: On the basis of biomedical imaging of the filter debris,
      the captured material could not be identified as embolized particles from the
      carotid plaque. On histological analysis the debris consisted mainly of red blood
      cell aggregates and/ or platelets, occasionally accompanied by granulocytes. We
      found no consistent histological evidence of embolized particles originating from
      atherosclerotic plaques. Post-procedure, three neurological events were reported:
      two (3.4%) transient ischemic attacks (TIA) and one (1.7%) ipsilateral minor
      stroke. CONCLUSION: The filters used during CAS in asymptomatic patients planned
      for cardiac surgery often remained empty. These findings may be explained by
      assuming that asymptomatic patients feature a different atherosclerotic plaque
      composition or stabilization through antiplatelet medication. Larger, randomized
      trials are clearly warranted, especially in the asymptomatic population.

PMID- 21953788
TI  - Keeping it in the family: three relatives with HbSC disease and simultaneous
      acute pulmonary emboli.

PMID- 21953789
TI  - Differential response of speed, amplitude, and rhythm to dopaminergic medications
      in Parkinson's disease.
AB  - Although movement impairment in Parkinson's disease includes slowness
      (bradykinesia), decreased amplitude (hypokinesia), and dysrhythmia, clinicians
      are instructed to rate them in a combined 0-4 severity scale using the Unified
      Parkinson's Disease Rating Scale motor subscale. The objective was to evaluate
      whether bradykinesia, hypokinesia, and dysrhythmia are associated with
      differential motor impairment and response to dopaminergic medications in
      patients with Parkinson's disease. Eighty five Parkinson's disease patients
      performed finger-tapping (item 23), hand-grasping (item 24), and pronation
      supination (item 25) tasks OFF and ON medication while wearing motion sensors on
      the most affected hand. Speed, amplitude, and rhythm were rated using the
      Modified Bradykinesia Rating Scale. Quantitative variables representing speed
      (root mean square angular velocity), amplitude (excursion angle), and rhythm
      (coefficient of variation) were extracted from kinematic data. Fatigue was
      measured as decrements in speed and amplitude during the last 5 seconds compared
      with the first 5 seconds of movement. Amplitude impairments were worse and more
      prevalent than speed or rhythm impairments across all tasks (P < .001); however,
      in the ON state, speed scores improved exclusively by clinical (P < 10(-6) ) and
      predominantly by quantitative (P < .05) measures. Motor scores from OFF to ON
      improved in subjects who were strictly bradykinetic (P < .01) and both
      bradykinetic and hypokinetic (P < 10(-6) ), but not in those strictly
      hypokinetic. Fatigue in speed and amplitude was not improved by medication.
      Hypokinesia is more prevalent than bradykinesia, but dopaminergic medications
      predominantly improve the latter. Parkinson's disease patients may show different
      degrees of impairment in these movement components, which deserve separate
      measurement in research studies. (c) 2011 Movement Disorder Society.

PMID- 21953790
TI  - Noninvasive monitoring of adrenocortical function in captive jaguars (Panthera
      onca).
AB  - Jaguars are threatened with extinction throughout their range. A sustainable
      captive population can serve as a hedge against extinction, but only if they are
      healthy and reproduce. Understanding how jaguars respond to stressors may help
      improve the captive environment and enhance their wellbeing. Thus, our objectives
      were to: (1) conduct an adrenocorticotrophic hormone (ACTH) challenge to validate
      a cortisol radioimmunoassay (RIA) for noninvasive monitoring of adrenocortical
      function in jaguars; (2) investigate the relationship between fecal corticoid
      (FCM) and androgen metabolite (FAM) concentrations in males during the ACTH
      challenge; and (3) establish a range of physiological concentrations of FCMs for
      the proposed protocol. Seven jaguars (3 M, 4 F) received 500 IU/animal of ACTH.
      Pre- and post-ACTH fecal samples were assayed for corticoid (M and F) and
      androgen metabolites (M) by RIA. Concentrations of FCMs increased (P80.01) after
      ACTH injection (pre-ACTH: 0.90 +/- 0.12 ug/g dry feces; post-ACTH: 2.55 +/- 0.25
      ug/g). Considering pre- and post-ACTH samples, FCM concentrations were higher
      (P80.01) in males (2.15 +/- 0.20 ug/g) than in females (1.30 +/- 0.20 ug/g), but
      the magnitude of the response to ACTH was comparable (P>0.05) between genders.
      After ACTH injection, FAMs increased in two (of 3) males; in one male, FCMs and
      FAMs were positively correlated (0.60; P80.01). Excretion of FCMs was assessed in
      16 jaguars (7 M, 9 F) and found to be highly variable (range, 80.11-1.56 ug/g).
      In conclusion, this study presents a cortisol RIA for monitoring adrenocortical
      function in jaguars noninvasively.

PMID- 21953791
TI  - Neuroendocrine regulation of food intake.
AB  - Despite a global obesity epidemic suggesting that human physiology is unable to
      prevent unhealthy gains in body weight, ample evidence indicates that weight can
      be tightly regulated. Food intake regulation is complex and in this article we
      will present a basic endocrine feedback loop model of energy homeostasis. Next,
      integration of long-term regulation with short-term, meal specific regulation and
      satiety will be discussed. Finally, the role of adiposity signals in modulation
      of food reward will be highlighted. A basic understanding of the structure
      function of these systems will inform the challenges of clinical care for those
      with disorders of energy balance.

PMID- 21953792
TI  - Neuroprotective effect of Rhizoma Atractylodis macrocephalae against
      excitotoxicity-induced apoptosis in cultured cerebral cortical neurons.
AB  - Excitotoxicity has been implicated in neurological disorders. This study
      investigated the neuroprotective effect of the extract from Rhizoma Atractylodis
      macrocephalae on excitotoxicity-induced neuronal apoptosis in primary cultured
      cerebral cortical neurons. Excitotoxicity was induced by exposure of cortical
      neurons to glutamate. Neuronal apoptosis and the protective effect of Rhizoma
      Atractylodis macrocephalae extract were examined by multi-indices including cell
      viability assay, morphological features, DNA fragmentation and flow cytometric
      analysis. After exposure of cultured neurons to glutamate for 24 h, the neurons
      exhibited marked apoptotic-like death. Co-treatment of the neurons with glutamate
      and Rhizoma Atractylodis macrocephalae extract significantly elevated the cell
      viability, and reduced the number of apoptotic cells. These results demonstrate
      that Rhizoma Atractylodis macrocephalae is an effective neuroprotective agent
      against glutamate-induced excitotoxicity and may have therapeutic potential in
      excitotoxicity-mediated diseases.

PMID- 21953793
TI  - Diffusion-weighted MRI: role in detecting abdominopelvic internal fistulas and
      sinus tracts.
AB  - PURPOSE: To retrospectively determine the incremental value of diffusion-weighted
      MR-imaging (DW-MRI) to T2-weighted (T2w) images in diagnosis of internal fistulas
      (IFs) and sinus tracts (STs). MATERIALS AND METHODS: Fourteen patients with 25
      IFs and STs arising from the small bowel (20), colon (4) and biliary tract (1)
      were included. Two independent observers reviewed T2w images, T2w+DW-MRI images
      and T2w+contrast enhanced T1-weighted (CE T1w) images at three sessions to detect
      IF/ST based on a confidence scale of five. Sensitivity and confidence score of
      each session was compared. RESULTS: 10/25 (40%) and 9/25 (36%) IFs and STs were
      detected on T2w images by observer 1 and 2, respectively. Both observers detected
      19/25 (76%) and 24/25(96%) IFs and STs on T2w+DW-MRI and T2w+CE T1w images,
      respectively. Detection rate and confidence score improved significantly by
      combining T2w images with DW-MRI or CE T1w images (reader 1 + 2: P <= 0.01).
      There was no significant difference between the IF/ST detection rate of T2w+DW
      MRI and T2w+CE T1 image combinations. Confidence scores with T2w+CE T1w images
      were significantly greater than DW-MRI+T2w images (reader 1:P = 0.01; reader 2: P
      = 0.03). CONCLUSION: DW-MRI showed additional value to T2w imaging for diagnosis
      of IF and ST. DW-MRI can be a useful adjunct, especially for patients with renal
      failure.

PMID- 21953794
TI  - Electron-accepting 6,12-diethynylindeno[1,2-b]fluorenes: synthesis, crystal
      structures, and photophysical properties.

PMID- 21953795
TI  - The role of vascular calcification in inducing fatigue and fracture of coronary
      stents.
AB  - Traditional approaches for in-vitro pulsatile and fatigue testing of endovascular
      stents do not take into consideration the pathologies of the stented vessel and
      their associated biomechanical effects. One important pathology is calcification,
      which may be capable of inducing changes in the vessel wall leading to
      inhomogeneous distribution of stresses combined with wall motion during the
      cardiac cycle. These local property changes in the region adjacent to stents
      could directly influence in-vivo stent performance. Seven cases containing a
      total of 18 stents were obtained from autopsy. Radiographs were evaluated and
      vessels were sectioned for histology and stent topographical analysis. Stents
      were retrieved by chemical removal of surrounding tissue and surfaces were
      evaluated using 3D digital optical and scanning electron microscopy for
      biomechanical abrasion and fracture features. Pathologic complications such as
      restenosis and thrombus formation were assessed from histological sections.
      Direct evidence of fracture was found in 6 of the 7 cases (in 12 out of 18
      stents; 9 drug eluting and 3 bare metal). The degree of stent alterations was
      variable, where separation of segments due to fracture occurred mostly in drug
      eluting stents. All fracture surfaces were representative of a high cycle fatigue
      mechanism. These fractures occurred in complex lesions involving the presence of
      diffuse calcification alone, or in combination with vessel angulations and
      multiple overlapping stents. Morphologic analysis of tissue at or near some
      fracture sites showed evidence of thrombus formation and/or neointimal tissue
      growth.

PMID- 21953796
TI  - Baroreflex sensitivity and its response to deep breathing predict increase in
      blood pressure in type 1 diabetes in a 5-year follow-up.
AB  - OBJECTIVE: We have recently demonstrated that early autonomic dysfunction,
      defined as low baroreflex sensitivity (BRS), could be functional and reversible.
      However, potential temporal changes in BRS have not yet been addressed by
      longitudinal studies in type 1 diabetes. Moreover, it is not known whether low
      BRS predisposes to hypertension or other nonfatal diabetes complications.
      RESEARCH DESIGN AND METHODS: We conducted a 5-year prospective study including 80
      patients with type 1 diabetes. We measured ambulatory blood pressure and
      autonomic function tests. BRS was assessed by six different methods during
      spontaneous, controlled, and slow deep breathing at baseline and follow-up.
      RESULTS: Spontaneous BRS declined over time (BRS(average) 16.2 +/- 0.8 vs. 13.2
      +/- 0.8 ms/mmHg; P < 0.01), but the change was not significant when adjusted for
      time of follow-up. Low BRS at baseline did not progress to cardiac autonomic
      neuropathy but predicted an increase in the nighttime systolic blood pressure
      (BRS(average) r = -0.37; P < 0.05). Additionally, BRS response to deep breathing
      at baseline predicted an increase in 24-h ambulatory blood pressure (BRS-alphaLF
      r = 0.323-0.346; P < 0.05). CONCLUSIONS: The decline in spontaneous BRS over time
      in patients with type 1 diabetes seems to be due to normal aging, which supports
      a functional etiology behind early autonomic derangements. Decreased resting BRS
      and the magnitude of improvement by deep breathing may be due to sympathovagal
      imbalance, a well-known mechanism in the development of hypertension. Early
      interventions aiming to reduce sympathetic overactivity in patients with low BRS
      might delay the development of hypertension.

PMID- 21953797
TI  - Low glycated hemoglobin and liver disease in the U.S. population.
AB  - OBJECTIVE: To characterize the association of low HbA(1c) values (<4.0%) with
      liver enzymes and steatosis. RESEARCH DESIGN AND METHODS: Cross-sectional study
      of 12,533 participants without diabetes aged <20 years in the Third National
      Health and Nutrition Examination Survey (1988-1994). Logistic regression models
      were adjusted for demographic, lifestyle, and health status variables. RESULTS:
      HbA(1c) values ranged from 3.2 to 15.7%, and 84 participants had HbA(1c) <4.0% in
      the population (mean age 44, 52% female, 15% black or Hispanic). We observed J
      shaped associations between HbA(1c) and liver enzymes and hepatic steatosis. In
      adjusted models, HbA(1c) <4.0% was strongly associated with elevated alanine
      aminotransferase (OR 3.62 [95% CI 1.09-12.02]) and aspartate aminotransferase
      (6.80 [2.99-15.43]). CONCLUSIONS: Low HbA(1c) values were associated with liver
      enzymes and steatosis in the U.S. population. Liver disease may partially explain
      the association of HbA(1c) with mortality and other long-term outcomes.

PMID- 21953798
TI  - Elevated liver function enzymes are related to the development of prediabetes and
      type 2 diabetes in younger adults: the Bogalusa Heart Study.
AB  - OBJECTIVE: Elevations in alanine aminotransferase (ALT) and gamma-glutamyl
      transferase (GGT), surrogate markers of liver dysfunction and nonalcoholic fatty
      liver, are considered as part of metabolic syndrome and related type 2 diabetes.
      However, information is limited regarding the long-term predictability of ALT and
      GGT in the development of prediabetes and type 2 diabetes. RESEARCH DESIGN AND
      METHODS: In this retrospective cohort study, normoglycemic (n = 874), prediabetic
      (n = 101), and diabetic (n = 80) adults aged 26-50 years (average age 41.3 years)
      were followed over an average period of 16 years since their young adulthood
      (aged 18-38 years, average age 25.1 years), with measurements of cardiometabolic
      risk factor variables including ALT and GGT. RESULTS: The follow-up prevalence
      rate of adult diabetes status by quartiles of baseline ALT and GGT levels showed
      an adverse trend for both prediabetes (P < 0.05) and diabetes (P < 0.01). In a
      longitudinal multivariate logistic regression analysis that included
      anthropometric, hemodynamic, and metabolic variables, as well as alcohol
      consumption and smoking, individuals with elevated baseline ALT and GGT levels
      (per 1-SD increment) were 1.16 and 1.20 times, respectively, more likely to
      develop diabetes (P = 0.05 for ALT and P < 0.01 for GGT); no such associations
      were noted for prediabetes. Regarding the predictive value of ALT and GGT, the
      area under the receiver operating curve analysis yielded C values ranging from
      0.70 to 0.82, with values significantly higher for diabetes compared with
      prediabetes. CONCLUSIONS: These findings in younger adults suggest potential
      clinical utility of including ALT and GGT as biomarkers in diabetes risk
      assessment formulations.

PMID- 21953799
TI  - Optimizing insulin glargine plus one injection of insulin glulisine in type 2
      diabetes in the ELEONOR study: similar effects of telecare and conventional self
      monitoring of blood glucose on patient functional health status and treatment
      satisfaction.
AB  - OBJECTIVE: To determine the functional health status and treatment satisfaction
      in patients with type 2 diabetes from the Evaluation of Lantus Effect ON
      Optimization of use of single dose Rapid insulin (ELEONOR) study that
      investigated whether a telecare program helps optimization of basal insulin
      glargine with one bolus injection of insulin glulisine. RESEARCH DESIGN AND
      METHODS: Functional health status and treatment satisfaction were investigated
      using the 36-Item Short-Form (SF-36) Health Survey, the World Health Organization
      Well-Being Questionnaire (WBQ), and the Diabetes Treatment Satisfaction
      Questionnaire. RESULTS: Of 291 randomized patients, 238 completed the study
      (telecare: 114; self-monitoring blood glucose: 124). Significant improvements
      were detected in most SF-36 domains, in WBQ depression and anxiety scores, and in
      treatment satisfaction, without differences between study groups. CONCLUSIONS: An
      insulin regimen that substantially improves metabolic control, while minimizing
      the risk of hypoglycemia, can positively affect physical and psychologic well
      being and treatment satisfaction irrespective of the educational support system
      used.

PMID- 21953801
TI  - Depressive symptoms, antidepressant medication use, and insulin resistance: the
      PPP-Botnia Study.
AB  - OBJECTIVE: Although insulin resistance (IR) may underlie associations between
      depressive symptoms and diabetes, previous findings have been contradictory. We
      examined whether depressive symptoms associate with IR and insulin secretion,
      and, additionally, whether antidepressant medication use may modulate such
      associations. RESEARCH DESIGN AND METHODS: A total of 4,419 individuals underwent
      an oral glucose tolerance test (OGTT). Participants with previously or newly
      diagnosed diabetes are excluded from this sample. The homeostasis model
      assessment of IR (HOMA-IR) and corrected insulin response (CIR) were calculated.
      Depressive symptoms and antidepressant medication use were self-reported.
      RESULTS: After controlling for confounding factors, depressive symptoms were
      associated with higher fasting and 30-min insulin during the OGTT and higher HOMA
      IR but not CIR. Antidepressant medication use failed to modify these
      associations. CONCLUSIONS: Depressive symptoms are associated with IR but not
      with changes in insulin response when corrected for IR in individuals without
      previously or newly diagnosed diabetes.

PMID- 21953800
TI  - Evaluation of nonfasting tests to screen for childhood and adolescent
      dysglycemia.
AB  - OBJECTIVE: To assess performance of nonfasting tests to screen children for
      dysglycemia (prediabetes or diabetes). RESEARCH DESIGN AND METHODS: This was a
      cross-sectional study of 254 overweight or obese (BMI >=85th percentile) children
      aged 10-17 years. Subjects came for two visits to a clinical research unit. For
      visit one, they arrived fasting and a 2-h glucose tolerance test and HbA(1c) and
      fructosamine testing were performed. For visit two, they arrived nonfasting and
      had a random plasma glucose, a 1-h 50-g nonfasting glucose challenge test (1-h
      GCT), and urine dipstick performed. The primary end point was dysglycemia
      (fasting plasma glucose >=100 mg/dL or a 2-h postglucose >=140 mg/dL). Test
      performance was assessed using receiver operating characteristic (ROC) curves and
      calculations of area under the ROC curve. RESULTS: Approximately one-half of
      children were female, 59% were white, and 30% were black. There were 99 (39%)
      cases of prediabetes and 3 (1.2%) cases of diabetes. Urine dipstick, HbA(1c)
      (area under the curve [AUC] 0.54 [95% CI 0.47-0.61]), and fructosamine (AUC 0.55
      [0.47-0.63]) displayed poor discrimination for identifying children with
      dysglycemia. Both random glucose (AUC 0.66 [0.60-0.73]) and 1-h GCT (AUC 0.68
      [0.61-0.74]) had better levels of test discrimination than HbA(1c) or
      fructosamine. CONCLUSIONS: HbA(1c) had poor discrimination, which could lead to
      missed cases of dysglycemia in children. Random glucose or 1-h GCT may
      potentially be incorporated into clinical practice as initial screening tests for
      prediabetes or diabetes and for determining which children should undergo further
      definitive testing.

PMID- 21953802
TI  - Acute-phase response reactants as objective biomarkers of radiation-induced
      mucositis in head and neck cancer.
AB  - BACKGROUND: Current evaluation of radiation-induced mucositis in head and neck
      cancer relies on subjective scoring with interrater variability. We evaluated
      serum erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as
      objective markers of radiation-induced mucositis. METHODS: Weekly serum CRP and
      ESR levels were measured in patients treated for head and neck cancer with
      radiation +/- chemotherapy. Acute radiation toxicity was evaluated using National
      Cancer Institute of Canada-Common Toxicity Criteria (NCIC-CTC) version 2.0 and
      the Head and Neck Radiotherapy Questionnaire (HNRQ). RESULTS: ESR and CRP levels
      were significantly elevated by 3 weeks (p = .01) and 6 weeks (p = .0002),
      respectively, and independent of age or pretreatment surgery. ESR was
      significantly dependent on radiation dose (p = .0004) and significantly higher
      with chemoradiation (p = .03). CONCLUSION: Serum ESR and CRP rise reliably in a
      radiation dose-dependent manner. ESR correlated with clinical symptoms and
      distinguished patients receiving chemoradiation. ESR and CRP may be an objective
      and sensitive marker of radiation-induced mucositis.

PMID- 21953803
TI  - Functionalized radioactive gold nanoparticles in tumor therapy.
AB  - The development of new treatment modalities that offer clinicians the ability to
      reduce sizes of tumor prior to surgical resection or to achieve complete ablation
      without surgery would be a significant medical breakthrough in the overall care
      and treatment of prostate cancer patients. The goal of our investigation is aimed
      at validating the hypothesis that Gum Arabic-functionalized radioactive gold
      nanoparticles (GA-(198) AuNP) have high affinity toward tumor vasculature. We
      hypothesized further that intratumoral delivery of the GA-(198) AuNP agent within
      prostate tumor will allow optimal therapeutic payload that will significantly or
      completely ablate tumor without side effects, in patients with hormone refractory
      prostate cancer. In order to evaluate the therapeutic efficacy of this new
      nanoceutical, GA-(198) AuNP was produced by stabilization of radioactive gold
      nanoparticles ((198) Au) with the FDA-approved glycoprotein, GA. This review will
      describe basic and clinical translation studies toward realization of the
      therapeutic potential and myriad of clinical applications of GA-(198) AuNP agent
      in treating prostate and various solid tumors in human cancer patients.

PMID- 21953804
TI  - Treatment of cotton with an alkaline Bacillus spp cellulase: activity towards
      crystalline cellulose.
AB  - We analysed the influence of several enzymatic treatment processes using an
      alkaline cellulase enzyme from Bacillus spp. on the sorption properties of cotton
      fabrics. Although cellulases are commonly applied in detergent formulations due
      to their anti-redeposition and depilling benefits, determining the mechanism of
      action of alkaline cellulases on cotton fibres requires a deeper understanding of
      the morphology and structure of cotton fibres in terms of fibre cleaning. The
      accessibility of cellulose fibres was studied by evaluating the iodine sorption
      value and by fluorescent-labelled enzyme microscopy; the surface morphology of
      fabrics was analysed by scanning microscopy. The action of enzyme hydrolysis over
      short time periods can produce fibrillation on cotton fibre surface without any
      release of cellulosic material. The results indicate that several short
      consecutive treatments were more effective in increasing the fibre accessibility
      than one long treatment. In addition, no detectable hydrolytic activity, in terms
      of reducing sugar production, was found.

PMID- 21953805
TI  - Modulation in the feeding prey capture of the ant-lion, Myrmeleon crudelis.
AB  - Ant-lions are pit-building larvae (Neuroptera: Myrmeleontidae), which possess
      relatively large mandibles used for catching and consuming prey. Few studies
      involving terrestrial arthropod larva have investigated prey capture behavior and
      kinematics and no study has shown modulation of strike kinematics. We examined
      feeding kinematics of the ant-lion, Myrmeleon crudelis, using high-speed video to
      investigate whether larvae modulate strike behavior based on prey location
      relative to the mandible. Based on seven capture events from five M. crudelis,
      the strike took 17.60 +/- 2.92 msec and was characterized by near-simultaneous
      contact of both mandibles with the prey. Modulation of the angular velocity of
      the mandibles based on prey location was clearly demonstrated. M. crudelis larvae
      attempted to simultaneously contact prey with both mandibles by increasing mean
      angular velocity of the far mandible (65 +/- 21 rad sec(-1) ) compared with the
      near mandible (35 +/- 14 rad sec(-1) ). Furthermore, kinematic results showed a
      significant difference for mean angular velocity between the two mandibles
      (P<0.005). Given the lengthy strike duration compared with other fast-striking
      arthropods, these data suggest that there is a tradeoff between the ability to
      modulate strike behavior for accurate simultaneous mandible contact and the
      overall velocity of the strike. The ability to modulate prey capture behavior may
      increase dietary breadth and capture success rate in these predatory larvae by
      allowing responsive adjustment to small-scale variations in prey size,
      presentation, and escape response.

PMID- 21953806
TI  - Room temperature and highly enantioselective additions of alkyltitanium reagents
      to aldehydes catalyzed by a titanium catalyst of (R)-H8-binol.
AB  - Three alkyltitanium reagents of RTi(O-i-Pr)3 (R = Cy (1a), i-Bu (1b), and n-Bu
      (1c)) were prepared in good yields. The high-resolution mass spectroscopy showed
      that and 1c in the gas phase are monomeric species. However, the solid state of
      1a revealed a dimeric structure. Asymmetric additions of 1a-1c to aldehydes
      catalyzed by a titanium catalyst of (R)-H8 -BINOL were studied at room
      temperature. The reactions produced desired secondary alcohols in good yields
      with good to excellent enantioselectivities of up to 94% ee. Reactivity and
      enantioselectivity differences, in terms of steric bulkiness of the R
      nucleophiles, are herein described. The addition reactions of secondary c-hexyl
      to aldehydes were slower than the reactions of primary i-butyl or n-butyl
      nucleophiles. For the primary alkyls, lower enantioselectivities were obtained
      for products from addition reactions of the linear n-butyl as compared with the
      enantioselectivities of products from the addition reactions of the branched i
      butyl group. The same stereochemistry of RTi(O-i-Pr)3 addition reactions as the
      addition reactions of organozinc, organoaluminum, Grignard, or organolithium
      reagents directly supports the argument of that titanium-catalyzed addition
      reactions of aldehydes involve an addition of an organotitanium nucleophile.

PMID- 21953807
TI  - Subjective memory complaints in community dwelling healthy older people: the
      influence of brain and psychopathology.
AB  - OBJECTIVES: Subjective memory complaints (SMC) are common. We aimed to
      characterize the relationship between psychiatric illness and white matter
      disease to SMC in a sample of healthy older people. MEASUREMENTS: Cognitively
      normal subjects between 55 and 90 years had age-adjusted and education-adjusted
      Consortium to Establish a Registry for Alzheimer's disease (CERAD) scores <=1.5
      SD from standard mean. ApoE genotyping was performed using polymerase chain
      reaction. Sixty subjects (30 SMC, 30 controls) underwent 3T MRI, which was rated
      by two raters blinded to the diagnosis, for periventricular (PVH) and deep white
      matter hyperintensities (DWMH) using the Fazekas scale. Subjective memory was
      assessed by asking the participant, Do you feel like your memory or thinking is
      becoming worse? RESULTS: Two hundred and fifteen volunteers were assessed. Ninety
      six were cognitively normal (mean age 62.5 years). SMC were reported by 52/96
      subjects (54%). These were compared with subjects who denied SMC. Participants
      with a history of depression or anxiety were more likely to have SMC (p = 0.02).
      The frequency distribution of ApoE4 allele and CERAD scores were similar. White
      matter load was similar (p <= 0.47), with a high prevalence of PVH and DWMH seen
      (100% and 88% of scans, respectively). CONCLUSION: Both SMC and white matter
      disease were common. SMC were associated with a history of depression or anxiety
      but not with white matter disease. Evaluation for a history of depression and
      anxiety in people with SMC is supported by these findings.

PMID- 21953808
TI  - Adalimumab for pyoderma gangrenosum associated with inflammatory bowel disease.

PMID- 21953809
TI  - Peptide-controlled access to the interior surface of empty virus nanoparticles.
AB  - The structure of Cowpea mosaic virus (CPMV) is known to high resolution, thereby
      enabling the rational use of the particles in diverse applications, from vaccine
      design to nanotechnology. A recently devised method for the production of empty
      virus-like particles (eVLPs) has opened up new possibilities for CPMV capsid
      based technologies, such as internal mineralisation of the particle. We have
      investigated the role of the carboxyl (C) terminus of the small coat (S) protein
      in controlling access to the interior of CPMV eVLPs by determining the efficiency
      of internal mineralisation. The presence of the C-terminal 24-amino acid peptide
      of the S protein was found to inhibit internal mineralisation, an effect that
      could be eliminated by enzymatic removal of this region. We have also
      demonstrated the amenability of the C terminus to genetic modification.
      Substitution with six histidine residues generated stable particles and
      facilitated external mineralisation by cobalt. These findings demonstrate
      consistent internal and external mineralisation of CPMV, and will aid the further
      exploration and development of the use of eVLPs for bionanotechnological and
      medical applications.

PMID- 21953810
TI  - Multicore assemblies potentiate magnetic properties of biomagnetic nanoparticles.

PMID- 21953811
TI  - Report of a new anomaly of the left anterior descending artery: type VI dual LAD.
AB  - A 48-year-old man with past medical history of coronary artery disease, previous
      angioplasty, hyperlipidemia, and generalized anxiety disorder presented with
      atypical chest pain. Coronary angiography and CT angiography revealed a variant
      dual left anterior descending (LAD) coronary artery not previously described.
      Spindola-Franco et al. have categorized dual LAD into four angiographic subtypes
      based on the origin and course of both a short- and a long branch of the LAD.
      Additionally, Manchanda et al. have described a novel variant of dual LAD with
      the short- and long LAD originating directly from the left and right coronary
      sinuses, respectively (Type V, see Table I). In the case presented, the long LAD
      arises from the right coronary artery and follows a unique route underneath the
      right ventricular outflow tract in the interventricular septal area to the
      anterior interventricular groove. We propose that this anatomy represents a new
      variant of dual LAD (Type VI).

PMID- 21953812
TI  - Orthogonal protein decoration of DNA nanostructures.
AB  - The development of robust DNA-protein coupling techniques is mandatory for
      applications of DNA nanostructures in biomedical diagnostics, fundamental
      biochemistry, and other fields in biomolecular nanosciences. The use of self
      labeling fusion proteins, which are orthogonal to biotin-streptavidin and
      antibody-antigen interactions, is described for the site-selective protein
      decoration of two exemplary DNA nanostructures: a four-way junction X-tile motif
      and a 3D DNA tetrahedron. Multifunctional DNA superstructures bearing up to four
      different proteins are generated and characterized by electrophoresis and
      microplate-based functionality assays. Steric and electrostatic interactions are
      identified as critical parameters controlling the efficiency of DNA-protein
      ligation. The results indicate that this method is versatile and broadly
      applicable, not only for the functionalization of DNA architectures but also for
      the site-specific decoration of other molecular materials and devices containing
      several different proteins.

PMID- 21953813
TI  - An iridium-stabilized, formally uncharged Te10 molecule with 3-center-4-electron
      bonding.
AB  - Te for 10: a tricyclic Te(10) molecule is stabilized in an iridium complex.
      Bonding analysis reveals 3-center-4-electron bonds in the linear Te(3) fragment.
      The tellurium atoms act as 2-electron donors to the transition-metal atoms.

PMID- 21953814
TI  - Visual misperceptions and hallucinations in Parkinson's disease: dysfunction of
      attentional control networks?
AB  - Visual misperceptions and hallucinations are a major cause of distress in
      patients with Parkinson's disease (PD), particularly in the advanced stages of
      the condition. Recent work has provided a framework for understanding the
      pathogenesis of these symptoms, implicating impairments from the retina to the
      integration of external information with preformed internal images. In this
      article, we propose a novel hypothesis that attempts to explain the presence of
      visual misperceptions and hallucinations in PD through the aberrant coordination
      of complimentary yet competing neural networks. We propose that hallucinations in
      PD reflect the relative inability to recruit activation in the dorsal attention
      network in the presence of an ambiguous percept, leading to overreliance on
      default mode network processing and salience arising from the ventral attention
      network. This inability is proposed to stem from improper function across
      cortical and subcortical structures secondary to the presence of Lewy body
      pathology. This hypothesis may be empirically tested by the use of targeted
      cognitive paradigms. In turn, this may assist our understanding of the
      pathophysiological mechanisms and cognitive processes contributing to visual
      misperceptions and hallucinations and ultimately may inform more effective
      treatment strategies for this troubling symptom.

PMID- 21953816
TI  - Measuring the neural response to continuous intramuscular infusion of hypertonic
      saline by perfusion MRI.
AB  - PURPOSE: To determine the extent to which arterial spin labeling (ASL), a
      functional magnetic resonance imaging technique that directly measures cerebral
      blood flow (CBF), is able to measure the neural activation associated with
      prolonged experimental muscle pain. MATERIALS AND METHODS: Hypertonic saline (HS)
      (5% NaCl) was infused into the brachioradialis muscle of 19 healthy volunteers
      for 15 min. The imaging volume extended from the dorsal side of the pons to the
      primary somatosensory cortices, covering most of the cortical and subcortical
      regions associated with pain perception. RESULTS: Using a numerical scale from 0
      to 10, ratings of pain intensity peaked at 5.9 +/- 0.5 (mean +/- SE). Group
      activation maps showed that the slow infusion of HS evoked CBF increases
      primarily in bilateral insula, with additional activation in right frontal
      regions. In the activated areas, CBF gradually increased at the onset of HS
      infusion and was maintained at relatively constant levels throughout the
      remainder of the infusion period. However, the level and extent of activation
      were smaller than observed in previous studies involving acute muscle pain.
      CONCLUSION: This study demonstrates the ability of ASL to measure changes in CBF
      over extended periods of time and that the neural activation caused by muscle
      pain is paradigm specific.

PMID- 21953815
TI  - Kikuchi-Fujimoto disease in fine-needle aspiration smears: a clinico-cytologic
      study of 76 cases of KFD and 684 cases of reactive hyperplasia of the lymph node.
AB  - Kikuchi-Fujimoto disease (KFD) is cytologically characterized by a polymorphous
      lymphoid cell population, abundant karyorrhectic debris and histiocytes, many of
      which are crescentic (Kikuchi histiocytes). As per reviewed literature, KFD may
      be confused with tuberculosis, lymphoma, and reactive hyperplasia of lymph nodes
      (RHLN). Since RHLN was found to be a major challenging factor during routine
      cytodiagnosis of KFD in our material, we tried to find out the differentiating
      clinico-cytologic features between 76 KFD and 684 RHLN cases seen in Kuwait.
      63.2% of KFD were in 3rd and 4th decades of life as compared to 40.2% of RHLN (P
      = 0.0002). Male to female ratio was 1: 2.45 for KFD and 1:1.09 for RHLN (P =
      0.0022). Kuwaiti:non-Kuwaiti ratio was 1:2.04 for KFD and 1.31:1 for RHLN (P <
      0.0001). Capillary networks was present in 71.1% of KFD smears and 52.6% of RHLN
      (P = 0.0023). Tingible body macrophages and dendritic reticulum cells were
      detected in 17.1% and 22.4%, respectively, in KFD as opposed to 50.1% and 58.8%,
      respectively, in RHLN (P < 0.0001). Kikuchi histiocyte count ranged from 2 to 36%
      in KFD and was >=10% in 31 (40.8%). Rare Kikuchi histiocytes were detected in 16
      (2.3%) of RHLN cases but in none of them the count exceeded 1%, whereas their
      count was >1% in all KFD cases (P < 0.0001). Thus, KFD cases differed
      significantly from RHLN in respect of age and sex distribution, Kuwaiti:non
      Kuwaiti ratio, and cytomorphologic features such as capillary networks, Kikuchi
      histiocyte count, dendritic reticulum cells, and tingible body macrophages.

PMID- 21953817
TI  - Effect of various dating formulae on sonographic estimation of gestational age in
      extremely preterm infants.
AB  - OBJECTIVES: Gestational age (GA) is one of the most important obstetric factors
      and prediction of date of delivery is usually based on ultrasonographic fetal
      measurements. Our aim was to determine whether applying three different dating
      formulae to a cohort of extremely preterm infants influenced the estimation of
      their GA. METHODS: This was a study of 513 infants delivered before 27
      gestational weeks, included in a Swedish national population study (EXPRESS),
      with information available on mid-trimester ultrasonographically measured
      biparietal diameter and femur length. We applied using these parameters three
      dating formulae, the Persson & Weldner formula, commonly used in Sweden, the
      Hadlock formula and the Mul formula, and compared their GA estimates to the
      clinically reported GA (recorded at delivery) and the last menstrual period (LMP)
      based GA. RESULTS: The mean reported GA was 173.2 days, corresponding well to the
      GA according to the Persson & Weldner dating formula (173.3). The mean GA
      according to LMP, the Hadlock formula and the Mul formula were 176.8, 175.3 and
      175.6 days, respectively. The Hadlock and Mul GA estimates differed significantly
      from that based on the Persson & Weldner formula (both P-values < 10(-6)). Among
      68 pregnancies with a reported duration of 22 weeks, 33 (49%) had a duration of
      23 weeks or more when GA was calculated according to LMP and 22 (32%) when GA was
      calculated according to the Hadlock formula. CONCLUSION: Estimated GA among
      infants delivered before 27 gestational weeks varied significantly depending on
      the dating formula used to calculate the estimated date of delivery; this might
      influence the clinical management of extremely preterm fetuses and infants.

PMID- 21953818
TI  - Coupling tetracyanoquinodimethane to tetrathiafulvalene: a fused TCNQ-TTF-TCNQ
      triad.

PMID- 21953819
TI  - Signet-ring plasma cell myeloma.

PMID- 21953820
TI  - Determination of bismuth in pharmaceutical products using phosphoric acid as
      molecular probe by resonance light scattering.
AB  - A novel method for the sensitive determination of bismuth(III) in pharmaceutical
      products using phosphoric acid as a molecular probe by resonance light scattering
      (RLS) is discussed. In 0.5 mol/L phosphoric acid (H3 PO4) medium, bismuth(III)
      reacted with PO4 (3-) to form an ion association compound, which resulted in the
      significant enhancement of RLS intensity and the appearance of the corresponding
      RLS spectral characteristics. The maximum scattering peak of the system existed
      at 364 nm. Under optimal conditions, there was linear relationship between the
      relative intensity of RLS and concentration of bismuth(III) in the range of 0.06
      10.0 ug/mL for the system. A low detection limit for bismuth(III) of 3.22 ng/mL
      was achieved. The relative standard deviations (RSD) for the determination of
      0.40 and 0.80 ug/mL bismuth(III) were 2.1% and 1.1%, respectively, for five
      determinations. Based on this fact, a simple, rapid, and sensitive method was
      developed for the determination of bismuth(III) at nanogram level by RLS
      technique with a common spectrofluorimeter. This analytical system was
      successfully applied to determine the trace amounts of bismuth(III) in
      pharmaceutical products, which was in good agreement with the results obtained by
      atomic absorption spectrometry (AAS).

PMID- 21953821
TI  - Reversal effects of components from the fruits of Illicium simonsii on human
      Adriamycin-resistant MCF-7 and 5-fluorouracil-resistant Bel7402 cells.
AB  - Twenty-one compounds including seven characteristic sesquiterpene lactones were
      isolated from Illicium simonsii and screened in vitro for their potential to
      restore the sensitivity of Adriamycin (ADR) resistant breast cancer cells (MCF
      7/ADR) and 5-fluorouracil-resistant hepatocellular carcinoma cells (Bel7402/5-FU)
      to ADR and 5-fluorouracil, respectively. These compounds were found to be non
      toxic to a panel of tumour cell lines: human breast cancer cells (MCF-7),
      cervical cancer cells (HeLa), hepatic liver carcinoma cells (HepG-2, Bel7402) and
      gastric carcinoma cells (BGC-823, SGC-7901). Five compounds showed an obvious
      decrease in the IC(50) of doxorubicin in MCF-7/ADR and four compounds sensitized
      Bel7402/5-FU to 5-fluorouracil at non-toxic concentrations. The relationship
      between the structure of these non-cytotoxic substances and their multidrug
      resistant (MDR) reversal abilities was investigated by principal component
      analysis (PCA) of the reversing fold (RF) values of these compounds and their
      calculated molecular descriptors of the tested substances. No correlations were
      found between the reversal potencies of these compounds to the two MDR cells.
      Compounds with lower polarity generally had stronger sensitizing ability to the P
      glycoprotein (Pgp) overexpressed MCF-7/ADR cells. On the other hand, higher
      hydrophilic compounds seemed to exhibit a stronger reversal effect to the MDR
      associated protein (MRP) overexpressed Bel7402/5-FU cell line. Our findings
      favoured further investigations on the active substances and the underlying
      mechanisms.

PMID- 21953822
TI  - Patterns of failure and histopathologic outcome predictors following definitive
      radiotherapy and planned neck dissection with residual disease.
AB  - BACKGROUND: Our aim was to report patterns of failure and histopathological
      predictors in patients with head and neck cancer treated by planned neck
      dissection. METHODS: We reviewed all new patients with head and neck cancer who
      underwent a planned neck dissection in our institution from 1998 to 2007.
      Patterns of failure after positive planned neck dissection were reported. The
      frequency and predictive value of histopathologic features were analyzed.
      RESULTS: Fifty positive planned neck dissection and 144 negative planned neck
      dissection cases were identified. The positive planned neck dissection cohort had
      lower 5-year overall survival (OS; 33% vs 77%; p < .01), a significantly higher
      distant metastasis (DM; 44% vs 11%; p < .01), a moderately lower local (86% vs
      96%; p < .01), and a similar regional control (94% vs 99%; p = .07) compared to
      the negative planned neck dissection cohort. Extracapsular extension/carcinoma
      within soft tissue and lymphovascular invasion were adverse survival predictors
      for patients with positive planned neck dissection on univariate and multivariate
      analysis. CONCLUSION: Positive planned neck dissection is associated with lower
      survival, predominantly attributed to significantly increased DM rather than
      reduced locoregional control.

PMID- 21953823
TI  - Review of UV spectroscopic, chromatographic, and electrophoretic methods for the
      cholinesterase reactivating antidote pralidoxime (2-PAM).
AB  - Pralidoxime (2-PAM) belongs to the class of monopyridinium oximes with
      reactivating potency on cholinesterases inhibited by phosphylating
      organophosphorus compounds (OPC), for example, pesticides and nerve agents. 2-PAM
      represents an established antidote for the therapy of anticholinesterase
      poisoning since the late 1950s. Quite high therapeutic concentrations in human
      plasma (about 13 ug/ml) lead to concentrations in urine being about 100 times
      higher allowing the use of less sensitive analytical techniques that were used
      especially in the early years after 2-PAM was introduced. In this time (mid-1950s
      until the end of the 1970s) 2-PAM was most often analyzed by either paper
      chromatography or simple UV spectroscopic techniques omitting any sample
      separation step. These methods were displaced completely after the establishment
      of column liquid chromatography in the early 1980s. Since then, diverse
      techniques including cation exchange, size-exclusion, reversed-phase, and ligand
      exchange chromatography have been introduced. Today, the most popular method for
      2-PAM quantification is ion pair chromatography often combined with UV detection
      representing more than 50% of all column chromatographic procedures published.
      Furthermore, electrophoretic approaches by paper and capillary zone
      electrophoresis have been successfully used but are seldom applied. This review
      provides a commentary and exhaustive summary of analytical techniques applied to
      detect 2-PAM in pharmaceutical formulations and biological samples to
      characterize stability and pharmacokinetics as well as decomposition and
      biotransformation products. Separation techniques as well as diverse detectors
      are discussed in appropriate detail allowing comparison of individual preferences
      and limitations. In addition, novel data on mass spectrometric fragmentation of 2
      PAM are provided.

PMID- 21953824
TI  - Calcium phosphate bioceramics fabricated from extracted human teeth for tooth
      tissue engineering.
AB  - Bioceramic tooth powders were prepared via heat treatment of extracted human
      teeth using sintering temperatures between 600 degrees C and 1200 degrees C, and
      their properties were investigated for potential tooth tissue engineering. The
      sintered human tooth powders were characterized using thermal analysis
      (thermogravimetric analysis (TG) and differential thermal analysis (DTA)), field
      emission scanning electron microscopy, X-ray diffraction, energy dispersive X-ray
      spectroscopy, and Fourier transformed infrared (FTIR) spectroscopy. Additionally,
      the phase constitutions and chemical homogeneities of the composite samples were
      examined using a quantitative chemical analysis with inductively coupled plasma
      spectroscopy. The results revealed that the annealing process produced useful
      hydroxyapatite-based bioceramic biomaterials when annealed above 1000 degrees C.
      The FTIR spectra and the TG/DTA thermograms of the tooth powders indicated the
      presence of organic compounds, which were completely removed after annealing at
      temperatures above 1000 degrees C. The tooth powders annealed between 1000
      degrees C and 1200 degrees C had good characteristics as bioceramic biomaterials.
      Furthermore, the biocompatibility of each tooth powder was evaluated using in
      vitro and in vivo techniques; our results indicate that the prepared human tooth
      powders have great potential for tooth tissue engineering applications.

PMID- 21953825
TI  - A screening tool for therapeutic monoclonal antibodies: Identifying the most
      stable protein and its best formulation based on thioflavin T binding.
AB  - The lack of a fast selection method to identify the most stable protein is one of
      the major challenges for developing successful therapeutic protein formulations
      more rapidly. The swift and accurate detection of small amounts of aggregates is
      another problem since aggregates may trigger an immunological response and the
      aggregation decreases the biological activity of the antibody. Here we present an
      alternative method for initial screening of the aggregation propensity of
      proteins, using monoclonal antibodies (mAb) as an example and thioflavin T (ThT)
      binding. The major advantage of ThT binding is the short duration of testing
      compared with size-exclusion chromatography (SEC) measurements that can take 6
      months or more even under accelerated conditions. The tendency to aggregate of
      each therapeutic human mAb probed with the ThT assay, together with SEC, is
      employed to formulate the ranking of mAb aggregation. ThT binding can determine
      the propensity of proteins to aggregate in a few days, illustrating that ThT
      binding would be a valuable screening tool.

PMID- 21953826
TI  - Janus Kinase V617F mutation in cigarette smokers.
AB  - The JAK2 V617F mutation is responsible for the constitutive activation of the
      erythropoietin receptor signaling pathway in most cases of polycythemia vera
      (PV). The mutation has also been described in healthy people. As smoking may
      result in secondary polycythemia, the goal of this trial was to examine the
      effect of smoking on the prevalence of the JAK2 mutation and its correlation to
      erythrocytosis. The study was case-control. Hospitalized smokers (n = 81) and
      nonsmokers (n = 61) were recruited. Serum was drawn for complete blood count,
      erythropoietin, ferritin and venous blood gases. JAK2 mutation was analyzed by
      highly sensitive allele-specific Quantitative Real Time PCR. The JAK2 mutation
      was found in 29/81 (35.8%) of smokers in comparison to only 9/61 (14.8%) of the
      control group (P = 0.007). The frequency of the mutation among smokers who were
      positive for the JAK2 mutation had a mean of 6.78 * 10(-4) +/- 1.08 * 10(-3) vs.
      1.51 * 10(-4) +/- 2.04 * 10(-4) among nonsmokers (P = 0.027). Both frequencies
      are much lower than those found in PV. There was a medium correlation between
      older age and mutation frequency in nonsmokers (r= 0.67, P = 0.043). Hematocrit
      was higher in smokers (47.8 +/- 6 vs. 41.7 +/- 4.7, P < 0.0001), but no
      correlation was found to JAK2 mutation. In a cohort of hospitalized smokers and
      nonsmokers, JAK2 mutation was more prevalent and found in higher frequencies
      among smokers than nonsmokers. We suggest that accelerated erythropoiesis renders
      the cells susceptible to JAK2 mutation.

PMID- 21953827
TI  - Diet restriction and life history trade-offs in short- and long-lived species of
      Daphnia.
AB  - The life-extending effects of diet restriction are well documented. One
      evolutionary model that accounts for this widespread conservation is the resource
      allocation model, where the selected individuals are those that can delay
      reproduction during periods of resource limitation. In this study, we use closely
      related species of a model organism, Daphnia, with widely divergent lifespans to
      address the relationship between diet restriction and longevity and assess
      whether the relationships are owing to trade-offs between reproductive and
      somatic investment. Specifically, we conducted a common garden experiment and
      constructed reaction norms for lifespan, fecundity, and body size as a function
      of food concentration. Our study provides evidence that the short-lived species
      in our study, D. pulex, shows the classically observed relationship of enhanced
      lifespan in response to reduced diet intake, but does not divert resources to
      somatic maintenance at the expense of reproduction during chronic diet
      restriction. In contrast, we find no evidence that the long-lived species in our
      study, D. pulicaria, gains any life-extending effects through diet restriction.
      Combined, our results provide evidence that the resource allocation model is not
      sufficient to explain the evolution of diet-mediated lifespan plasticity.

PMID- 21953828
TI  - Comparison between two different methods of immobilizing NGF in poly(DL-lactic
      acid-co-glycolic acid) conduit for peripheral nerve regeneration by EDC/NHS/MES
      and genipin.
AB  - For surface modification and nerve regeneration, chitosan, followed by nerve
      growth factor (NGF), was immobilized onto the interior surface of poly (lactic
      acit-co-glycolic) conduits, using EDC/NHS/MES system (EDCs) and genipin (GP).
      Four new conduits were, therefore, obtained and named by immobilizing order
      EDCs/EDCs, GP/EDCs, EDCs/GP, and GP/GP groups. The immobilized methods used were
      evaluated and compared, respectively. The researchers found that the EDCs- and GP
      cross-linked chitosan displayed higher hydrophilic than pure poly (DL-lactic acid
      co-glycolic acid) (PLGA) in water contact angle experiment, which meant the cell
      compatibility was improved by the modification. Scanning electron microscopic
      observations revealed that the GP-cross-linking of chitosan greatly improved cell
      compatibility while cultured rat PC12 cells were flatter and more spindle-shaped
      than EDCs-cross-linked chitosan. The results concerning the GP-cross-linked
      chitosan revealed significant proliferation of the seeded cells relative to pure
      PLGA films, as determined by counting cells and MTT assay. The NGF was released
      from the modified conduits in two separate periods--an initial burst in 5 days
      and then slow release from day 10 to day 40. The GP/EDCs group had the highest
      NGF value among all groups after the 5th day. Finally, the controlled-release
      conduits were used to bridge a 10 mm rat sciatic nerve defect. Six weeks
      following implantation, morphological analysis revealed the highest numbers of
      myelinated axons in the midconduit and distal regenerated nerve in GP/EDCs group.
      Therefore, the results confirm that GP/EDCs groups with good cell compatibility
      and effective release of NGF can considerably improve peripheral nerve
      regeneration.

PMID- 21953829
TI  - Screening for tuberculosis and hepatitis B prior to the initiation of anti-tumor
      necrosis therapy.
AB  - BACKGROUND: Since the introduction of infliximab, anti-tumor necrosis factor
      alpha (anti-TNF-alpha) agents have been used with increasing frequency for the
      treatment of inflammatory bowel disease (IBD). Reactivation of latent
      Mycobacterium tuberculosis (TB) soon became recognized as a complication of
      therapy. More recently, reactivation of hepatitis B while on anti-TNF therapy has
      been documented. The aim of this study was to assess the adherence to screening
      for latent TB and hepatitis B by gastroenterologists prior to initiation of an
      anti-TNF. METHODS: This is a retrospective analysis of all patients with IBD
      treated with an anti-TNF at a large urban academic hospital. In our population,
      65% of patients were screened for latent TB prior to the initiation of anti-TNF
      therapy, while 25% of patients were screened for hepatitis B. RESULTS: Failure to
      screen for latent TB was strongly correlated with prior exposure to an anti-TNF
      (odds ratio [OR]: 5.3; P < 0.0001) and initiation of treatment prior to 2006 (OR:
      5.8; P < 0.0001). Failure to screen for hepatitis B was associated with lack of
      an abnormal alanine aminotransferase (OR: 2.6; P = 0.005) and treatment prior to
      2010 (OR: 3.3; P = 0.02). Providers who had been in practice longer were less
      likely screen for TB or hepatitis B. CONCLUSIONS: The rate of screening for both
      latent TB and hepatitis B in this study was inadequate. While the rate of
      screening is increasing, further systems improvements and physician education is
      needed.

PMID- 21953830
TI  - Additional criterion for the determination of the handedness of 2(1) helices in
      crystals of bile acids: Crystal structure of a tert-butylphenyl derivative of
      cholic acid.
AB  - [3beta,5beta,7alpha,12alpha]-3-(4-t-Butylbenzoilamine)-7,12-dihydroxycholan-24
      oic acid was synthesized and recrystallized from chlorobenzene and acetone.
      Orthorhombic P2(1)2(1)2(1) and monoclinic P2(1) crystals were obtained,
      respectively, and both crystals include solvent and water molecules with a 1:1:1
      stoichiometry. In the second case, there are two nonequivalent molecules of the
      steroid in the unit cell. In both crystals, a crossing structure results for the
      molecular packing, stabilized by hydrogen bonds between the steroid molecules. In
      the second crystal, water links steroid molecules of the same type, which are not
      directly connected through hydrogen bonds. The steroid molecules define
      helicoidal assemblies along 2(1) screw axes. The handedness in the crystal in
      chlorobenzene is unambiguously defined by following the criterion proposed by
      Miyata et al., as the steroids are in a belly-to-belly disposition around the
      axis. This motif does not appear in the crystal in acetone, and other criterion
      is required. On the basis of the fact that a staircase and its banister have the
      same handedness and using the crystal in chlorobenzene as reference, the
      additional criterion has been established. According to it, in the absence of a
      belly-to-belly orientation, the handedness must be defined by keeping the bile
      acid with its right side oriented toward the axis. Pitch angles of the helices
      and tilt angles of the molecules are also determined.

PMID- 21953831
TI  - Explaining ADAGIO: a critical review of the biological basis for the clinical
      effects of rasagiline.
AB  - The ADAGIO study demonstrated a symptomatic benefit for rasagiline in early
      Parkinson's disease (PD) and suggested a disease-modifying effect. Evidence
      indicates that mitochondrial dysfunction plays a role in the pathogenesis of PD
      and that this may be the site of effect for rasagiline. In this systematic
      review, evidence for the role of mitochondria in the pathogenesis of PD are
      reviewed in light of other proposed mechanisms of neuronal degeneration and the
      actions of rasagiline and its component parts, namely propargylamine and the
      metabolite, aminoindan. Evidence for the role of mitochondria in the pathogenesis
      and treatment of PD are reviewed in light of other proposed mechanisms of
      neuronal degeneration and clinical actions of rasagiline. Monoamine oxidase B
      (MAO-B) located in the outer mitochondrial membrane controls dopamine metabolism
      in early PD, and this is the likely location for the symptomatic action of
      rasagiline. Accumulating evidence indicates that mitochondrial impairment
      contributes to dopaminergic neuronal loss in PD, either directly or through other
      mechanisms such as oxidative stress or protein misfolding. Further rasagiline
      affects numerous mitochondrial mechanisms that prevent apoptotic cell death
      including prevention of opening of the mitochondrial transition pore, decreased
      release of cytochrome C, alterations in pro-antiapoptotic genes and proteins, and
      the nuclear translocation of glyceraldehyde 3-phosphate dehydrogenase (GAPDH).
      Thus, the functional neuroprotective actions of rasagiline may not be dependent
      on MAO-B inhibition, but rather may involve actions of the propargylamine moiety
      and the aminoindan metabolite. An accumulating body of literature indicates a
      mitochondrial site of action for rasagiline and highlights the neuroprotective
      action of the drug, providing strong biological plausibility for disease
      modifying effects of the drug such as those observed in ADAGIO.

PMID- 21953832
TI  - Graphene transistor arrays for recording action potentials from electrogenic
      cells.

PMID- 21953833
TI  - Physical vapor deposition of metal nanoparticles on chemically modified graphene:
      observations on metal-graphene interactions.
AB  - The growth of metallic nanoparticles formed on chemically modified graphene (CMG)
      by physical vapor deposition is investigated. Fine control over the size (down to
      ~1.5 nm for Au) and coverage (up to 5 * 10(4)  MUm(-2)  for Au) of nanoparticles
      can be achieved. Analysis of the particle size distributions gives evidence for
      Au nanocluster diffusion at room temperature, while particle size statistics
      differ clearly between metal deposited on single- and multilayer regions. The
      morphology of the nanoparticles varies markedly for different metals (Ag, Au, Fe,
      Pd, Pt, Ti), from a uniform thin film for Ti to a droplet-like growth for Ag. A
      simple model explains these morphologies, based only on consideration of 1) the
      different energy barriers to surface diffusion of metal adatoms on graphene, and
      2) the ratio of the bulk cohesive energy of the metal to the metal-graphene
      binding energy. Understanding these interactions is important for controlling
      nanoparticle and thin-film growth on graphene, and for understanding the
      resultant charge transfer between metal and graphene.

PMID- 21953834
TI  - Ultrasonographic fetal head position to predict mode of delivery: a systematic
      review and bivariate meta-analysis.
AB  - OBJECTIVE: We performed a systematic review to determine whether sonographic
      assessment of occipital position of the fetal head can contribute to the
      prediction of the mode of delivery. METHODS: We performed a systematic literature
      search of electronic databases from inception to May 2011. Two reviewers
      independently extracted data from the included studies. We used a bivariate model
      to estimate point estimates for sensitivity and specificity curves for the
      outcome Cesarean delivery. Eligible studies were cohort studies or cross
      sectional studies that reported on both the position of the fetal head, as
      assessed by ultrasound, before or at the beginning of active labor as well as the
      outcome of labor in women at term. RESULTS: We included 11 primary articles
      reporting on 5053 women, of whom 898 had a Cesarean section. All studies
      indicated disappointing values for sensitivity and specificity in the prediction
      of Cesarean section. Summary point estimates of sensitivity and specificity were
      0.39 (95% CI, 0.32-0.48) and 0.71 (95% CI, 0.67-0.74), respectively. CONCLUSION:
      Sonographic assessment of occipital position of the fetal head before delivery
      should not be used in the prediction of mode of delivery.

PMID- 21953835
TI  - Direct investigation of the Aspergillus GDP-mannose transporter by STD NMR
      spectroscopy.

PMID- 21953836
TI  - Application of multiwalled carbon nanotubes/ionic liquid modified electrode for
      amperometric determination of sulfadiazine.
AB  - A highly sensitive amperometric sulfadiazine sensor based on coating multiwalled
      carbon nanotubes (MWCNTs) and N-octyl-pyridinium-hexafluorophosphate (OPPF(6))
      ionic liquid composite on a glassy carbon (GC) electrode is described. The
      MWCNTs/OPPF(6) composite contributed new properties to electrochemical sensors by
      combining the advantages of both ionic liquids and MWCNTs. Compared with bare GC
      electrode, the electrocatalytic activity of MWCNTs/OPPF(6) generated a greatly
      improved electrochemical detection of sulfadiazine including low oxidation
      potential, high current responses, and good anti-fouling performance. The
      oxidation peak currents of sulfadiazine obtained on the MWCNTs/OPPF(6) coated GC
      electrode were proportional to the concentration of sulfadiazine within the range
      of 3.3-35.4 MUM with a detection limit of 0.21 MUM.

PMID- 21953837
TI  - Regulated oxidation of nickel in multisegmented nickel-platinum nanowires: an
      entry to wavy nanopeapods.

PMID- 21953838
TI  - Comparative evaluation of two different Artemisia dracunculus L. cultivars for
      blood sugar lowering effects in rats.
AB  - Recent concerns about the potential carcinogenicity of estragole and
      methyleugenol led a number of regulatory bodies to call for restrictions on the
      use of herbs that contain these constituents. A number of medicinal plants
      produce essential oils that contain estragole and methyleugenol, including
      Artemisia dracunculus L. (tarragon). Previous studies have proven the
      antidiabetic properties of tarragon. In order to address the safety concerns of
      estragole containing tarragon extracts, an extraction procedure was developed to
      minimize the estragole and methyleugenol content in tarragon extracts and the
      ethanol versus aqueous extracts from two Artemisia dracunculus cultivars (French
      and Russian tarragon) were tested for blood glucose lowering effects in rats. It
      could be demonstrated that aqueous extracts of both Artemisia cultivars did not
      contain detectable amounts of estragole and methyleugenol, whereas ethanol
      extracts (60% v/v) of the French cultivar contained higher levels of the
      aforementioned compounds than those of the Russian cultivar. Further testing
      revealed that Russian tarragon lowered blood glucose levels in rats after glucose
      challenge, with the ethanol extract being as active as the aqueous extract. The
      results suggest that by using adequate production procedures the amount of
      potentially harmful compounds in extracts can be limited without affecting the
      overall pharmacological activities of these preparations.

PMID- 21953839
TI  - Silicon analogues of the nonpeptidic GnRH antagonist AG-045572: syntheses,
      crystal structure analyses, and pharmacological characterization.
AB  - AG-045572 (CMPD1, 1 a) is a nonpeptidic gonadotropin-releasing hormone (GnRH)
      antagonist that has been investigated for the treatment of sex hormone-related
      diseases. In the context of systematic studies on sila-substituted drugs, the
      silicon analogue disila-AG-045572 (1 b) and its derivative 2 were prepared in
      multi-step syntheses and characterized by elemental analyses (C, H, N), NMR
      spectroscopic studies (1H, 13C, 29Si), and single-crystal X-ray diffraction. The
      pharmacological properties of compounds 1 a, 1 b, and 2 were compared in terms of
      their in vitro potency at cloned human and rat GnRH receptors. Compounds 1 a and
      2 were also examined in regard to their pharmacokinetics and in vivo efficacy in
      both castrated rat (luteinizing hormone (LH) suppression) and intact rat
      (testosterone suppression) models. The efficacy and pharmacokinetic profiles of 1
      a and its silicon-containing analogue 2 appear similar, indicating that
      replacement of the 5,6,7,8-tetrahydronaphthalene ring system by the 1,3
      disilaindane skeleton led to retention of efficacy. Therefore, the silicon
      compound 2 represents a novel drug prototype for the design of potent, orally
      available GnRH antagonists suitable for once-daily dosing.

PMID- 21953840
TI  - Prevalence of pulmonary hypertension in hereditary spherocytosis.
AB  - Vascular complications, including pulmonary hypertension (PH), have been reported
      to occur following splenectomy for various disorders,including hereditary
      spherocytosis (HS). We performed a prospective cross-sectional study of 36 adults
      with HS (78% with prior splenectomy)utilizing echocardiography to estimate
      tricuspid regurgitant jet velocity (TRV) as well as measurement of N-terminal pro
      B-type natriuretic peptide (NT-proBNP) to screen for PH. No participant with HS
      hada significantly elevated TRV or NT-proBNP level, despite a median 25-year
      interval since splenectomy (95% confidence interval for point prevalence 0,
      0.097). Although our study was limited by a small sample size, it appears that
      persons with HS, following splenectomy, appear unlikely to be at significantly
      increased risk of developing PH to the degree reported for thalassemia and sickle
      cell disease

PMID- 21953841
TI  - Anti-EGFR-targeting agents in recurrent or metastatic head and neck carcinoma: a
      meta-analysis.
AB  - BACKGROUND: Anti-epidermal growth factor receptor (EGFR) therapies are effective
      in head and neck carcinoma. A meta-analysis was performed to assess their
      efficacy and safety in advanced head and neck carcinoma. METHODS: Six trials
      randomizing 2257 patients with recurrent/metastatic head and neck carcinoma for
      chemotherapy or best supportive care with or without anti-EGFR therapies were
      identified. The efficacy data included progression-free survival (PFS), overall
      survival (OS), response rate, and toxicity. RESULTS: The response rate was higher
      in the experimental arm (p < .0001; relative risk = 1.62). A significant PFS
      benefit (p < .0001; hazard ratio [HR] = 0.70) favored the anti-EGFR treatment.
      Survival was significantly increased if trials of monoclonal antibodies were
      included (p = .004; HR = 0.83). A higher incidence of diarrhea, skin rash,
      anorexia, and hypomagnesemia was observed. CONCLUSIONS: This meta-analysis
      suggests that in recurrent/metastatic head and neck cancer the addition of anti
      EGFR monoclonal antibodies to standard therapy confers a statistically
      significant improvement in OS, PFS, and overall response rate.

PMID- 21953842
TI  - Towards unimolecular luminescent solar concentrators: bodipy-based dendritic
      energy-transfer cascade with panchromatic absorption and monochromatized
      emission.

PMID- 21953843
TI  - A conductive nanostructured polymer electrodeposited on titanium as a
      controllable, local drug delivery platform.
AB  - Infection and inflammation associated with orthopedic implants can be life
      threatening, time consuming, and expensive, thus, motivating the development of a
      local drug delivery platform that could prevent such deleterious events. For this
      purpose, nanostructured polypyrrole (PPy) incorporating antibiotics and anti
      inflammatory drugs (penicillin/streptomycin (P/S) or dexamethasone (Dex),
      respectively) were coated on commercially pure titanium through an easy to use
      electrochemical deposition method. As shown in our previous study, about 80%
      (compared with initial amount) of these incorporated drugs were released after
      electrical stimulation spanning five cycles (voltage was varied between -1 V and
      1 V). In a further continuation of this work, nanostructured P/S incorporated PPy
      coatings on titanium were demonstrated to be bactericidal against Staphylococcus
      epidermis after 1 h, and when incorporated with Dex, inhibited macrophage (an
      inflammatory and immune response cell) growth after 8 and 13 h of in vitro
      culture. Moreover, nanostructured PPy-drug films coated on titanium enhanced
      osteoblast (bone forming cells) proliferation, while at the same time, suppressed
      fibroblast (fibrous tissue forming cells) proliferation for up to 5 days. After
      electrical stimulation, antimicrobial and anti-inflammatory-coated devices
      yielded lower bacteria colonies and macrophage growth compared with
      unincorporated-drug PPy films (controls). This study, thus, suggests that drug
      incorporated nanostructured PPy coatings on titanium are capable of effectively
      treating potential orthopedic implant infection and inflammation, and lays the
      foundation for the further development of local and controllable on-demand drug
      delivery coatings to improve orthopedic implant efficacy.

PMID- 21953844
TI  - Registration of epidemiological studies: benefits and risks.

PMID- 21953845
TI  - Registration of Observational Studies: perspectives from an industry-based
      epidemiology group.
AB  - Registration of randomized clinical trials has become standard practice and is
      enforced through publication policies and governmental regulations. However, the
      registration of observational studies remains controversial. In this commentary,
      we propose that a compromise can be reached on which observation should be
      registered based on study design and study intent.

PMID- 21953846
TI  - Inhaled corticosteroid adherence in paediatric patients: the PACMAN cohort study.
AB  - AIMS: Poor adherence with inhaled corticosteroids (ICSs) has been reported
      frequently and may be associated with uncontrolled asthma. A better understanding
      of factors influencing adherence may help to achieve higher adherence rates for a
      larger part of the population, which will eventually lead to better asthma
      control. The aim of this study was to investigate factors associated with
      adherence in paediatric ICS users. METHODS: We included 527 children using ICSs
      who participated in the Pharmacogenetics of Asthma Medication in Children:
      Medication with Anti-inflammatory Effects (PACMAN) cohort study. The outcome, a
      parent-reported adherence, was assessed by using the Medication Adherence Report
      Scale. Four categories of determinants were studied: child characteristics,
      family characteristics, medication use (parental beliefs towards medication;
      using Beliefs about Medicines Questionnaire) and environmental factors. RESULTS:
      Good adherence was observed in 302 children (57%). Increased fractional exhaled
      nitric oxide values (indication for airway inflammation) were associated with a
      lower chance of good adherence (OR = 0.25, 95%CI = 0.15-0.41). Parental necessity
      beliefs about medication were associated with higher adherence (OR = 2.32, 95%CI
      = 1.59-3.39). Dutch origin was also associated with higher adherence rates (OR =
      2.11, 95%CI = 1.09-4.07). Furthermore, younger age (< 6 years) was associated
      with better adherence (OR = 1.62, 95%CI = 1.02-2.59). CONCLUSIONS: Increased
      airway inflammation was associated with lower ICS adherence, which underlines the
      need of good adherence to reach disease control. Our results suggest that by
      improving knowledge, especially in ethnic minorities, and by stimulating positive
      parental perception towards the nature of the disease, the characteristics of the
      prescribed drugs and the use of medications, better adherence and as a result
      better asthma control could be reached.

PMID- 21953847
TI  - Re: Confounding adjustment via a semi-automated high-dimensional propensity score
      algorithm: an application to electronic medical records.

PMID- 21953849
TI  - Median nerve deformation in differential finger motions: ultrasonographic
      comparison of carpal tunnel syndrome patients and healthy controls.
AB  - We investigated the median nerve deformation in the carpal tunnel in patients
      with carpal tunnel syndrome and controls during thumb, index finger, middle
      finger, and a four finger motion, using ultrasound. Both wrists of 29
      asymptomatic volunteers and 29 patients with idiopathic carpal tunnel syndrome
      were evaluated by ultrasound. Cross-sectional images during motion from full
      extension to flexion were recorded. Median nerve cross-sectional area, perimeter,
      aspect ratio of the minimal enclosing rectangle, and circularity in extension and
      flexion positions were calculated. Additionally, a deformation index was
      calculated. We also calculated the intra-rater reliability. In both controls and
      patients, the median nerve cross-sectional area became significantly smaller from
      extension to flexion in all finger motions (p < 0.05). In flexion and extension,
      regardless of the specific finger motion, the median nerve deformation,
      circularity and the change in perimeter were all significantly greater in CTS
      patients than in controls (p < 0.05). We found excellent intra-rater reliability
      for all measurements (ICC > 0.84). With this study we have shown that it is
      possible to assess the deformation of the median nerve in carpal tunnel syndrome
      with ultrasonography and that there is more deformation of the median nerve in
      carpal tunnel syndrome patients during active finger motion. These parameters
      might be useful in the evaluation of kinematics within the carpal tunnel, and in
      furthering our understanding of the biomechanics of carpal tunnel syndrome in the
      future.

PMID- 21953850
TI  - Water-soluble argatroban for antithrombogenic surface coating of tissue
      engineered cardiovascular tissues.
AB  - Argatroban is a powerful synthetic anticoagulant, but due to its water-insoluble
      nature, it is unsuitable for use as a coating material to reduce the thrombogenic
      potential of natural or tissue-engineered blood-contacting cardiovascular
      tissues. On the other hand, anionic compounds could adsorb firmly onto connective
      tissues. Therefore, in this study, an anionic form of argatroban was prepared by
      neutralization from its alkaline solution, dialysis, and freeze-drying. The
      subsequently obtained argatroban derivative could be easily dissolved in water.
      Analysis of the surface chemical composition showed that the water-soluble
      argatroban (WSA) could be adsorbed on the entire surface of tissue-engineered
      connective tissue sheets composed mainly of collagen. Adsorption was achieved on
      immersion of the tissue-engineered connective tissue sheet in a saline/WSA
      solution for only 30 s without any change in the mechanical properties of the
      tissue-engineered sheets. Complete surface adsorption (ca., 1 mg/cm(2) ) was
      obtained at WSA concentrations of over 5 mg/mL. WSA adsorption was maintained for
      at least 7 days with rinsing. Blood coagulation was significantly prevented on
      the WSA-adsorbed surfaces in acute in vitro experiments. The coating was applied
      to in vivo tissue-engineered vascular grafts (biotubes) or tri-leaflet tissues
      (biovalves) under development, ensuring a high likelihood of nonthrombogenicity
      of their blood-contacting surfaces with high patency, at least in the subchronic
      phase. It appears that WSA satisfies the initial requirements for a biocompatible
      aqueous coating material for use in natural or tissue-engineered tissues.

PMID- 21953851
TI  - Bioactivity of compounds from Acmella oleracea against Tuta absoluta (Meyrick)
      (Lepidoptera: Gelechiidae) and selectivity to two non-target species.
AB  - BACKGROUND: Tropical plants are recognised sources of bioactive compounds that
      can be used for pest control. The objective of this study was to evaluate the
      biological activity of compounds present in Acmella oleracea (Asteracea) against
      Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae), which is the main pest of
      tomato crops in Latin America. The selectivity of these compounds to the predator
      Solenopsis saevissima (Smith) (Hymenoptera: Formicidae) and to the pollinator
      Tetragonisca angustula (Latr.) (Hymenoptera: Apidae: Meliponinae) was also of
      interest. RESULTS: A bioassay screening with hexane and ethanol extracts from 23
      plants was performed. The hexane extract of A. oleraceae was the most active of
      the extracts and was selected for further study. The following three alkamides
      were isolated from a hexane extract of the aerial parts of A. oleracea:
      spilanthol, (E)-N-isobutylundeca-2-en-8,10-diynamide and (R, E)-N-(2
      methylbutyl)undeca-2-en-8,10-diynamide. All of the isolated compounds showed
      insecticidal activity, with spilanthol being the most active (LD(50) = 0.13 ug
      mg(-1) ) against T. absoluta. The alkamides were selective to both beneficial
      species studied. CONCLUSION: The crude hexane extract of A. oleraceae showed high
      insecticidal activity and can be used to control T. absoluta in organic or
      conventional crops. Quantification of LD(50) values of isolated compounds against
      T. absoluta showed that alkamides could serve as potent insecticides for T.
      absoluta control programmes. Spilanthol was the main alkamide active isolated.
      This alkamide is the most promising as it has the highest insecticidal activity
      and is selective to non-target organisms.

PMID- 21953852
TI  - Utility of ultrasound-guided fine-needle aspiration in splenic lesions.
AB  - Indications of fine-needle aspiration (FNA) of spleen have increased as more
      splenic lesions are detected because of advanced imaging techniques. A
      retrospective analysis of cytological material of 36 patients on whom ultrasound
      guided splenic FNA was performed was done. No complications were noted. There
      were 16 inflammatory lesions, 12 neoplastic and 8 cases were reported as
      descriptive either because of scant cellularity, blood only, or normal splenic
      cytology. Inflammatory lesions included nine cases of acute abscess, five cases
      of tuberculosis, and one case each of leishmaniasis and infarct. Neoplastic
      lesions included two benign (benign cyst and inflammatory pseudotumor) and 10
      malignant lesions. Among malignant lesions, eight were non-Hodgkin lymphoma
      (NHL), one suspicious of NHL, and one desmoplastic small round cell tumor. FNA
      proved to be an effective procedure for reaching a microscopic tissue diagnosis
      and thus a splenectomy could be avoided in cases where it was not required.

PMID- 21953853
TI  - Residual vein thrombosis for assessing duration of anticoagulation after
      unprovoked deep vein thrombosis of the lower limbs: the extended DACUS study.
AB  - The safest duration of anticoagulation after idiopathic deep vein thrombosis
      (DVT) is unknown. We conducted a prospective study to assess the optimal duration
      of vitamin K antagonist (VKA) therapy considering the risk of recurrence of
      thrombosis according to residual vein thrombosis (RVT). Patients with a first
      unprovoked DVT were evaluated for the presence of RVT after 3 months of VKA
      administration; those without RVT suspended VKA, while those with RVT continued
      oral anticoagulation for up to 2 years. Recurrent thrombosis and/or bleeding
      events were recorded during treatment (RVT group) and 1 year after VKA withdrawal
      (both groups). Among 409 patients evaluated for unprovoked DVT, 33.2% (136 of 409
      patients) did not have RVT and VKA was stopped. The remaining 273 (66.8%)
      patients with RVT received anticoagulants for an additional 21 months; during
      this period of treatment, recurrent venous thromboembolism and major bleeding
      occurred in 4.7% and 1.1% of patients, respectively. After VKA suspension, the
      rates of recurrent thrombotic events were 1.4% and 10.4% in the no-RVT and RVT
      groups, respectively (relative risk = 7.4; 95% confidence interval = 4.9-9.9).
      These results indicate that in patients without RVT, a short period of treatment
      with a VKA is sufficient; in those with persistent RVT, treatment extended to 2
      years substantially reduces, but does not eliminate, the risk of recurrent
      thrombosis.

PMID- 21953854
TI  - Establishing bioequivalence of racemic venlafaxine formulations using
      stereoselective assay method: Is it necessary?
AB  - A bioequivalence study for venlafaxine generic formulation was conducted as an
      open label, balanced, randomized, two-way crossover, single-dose study. In this
      study, a comparison of various pharmacokinetic parameters of venlafaxine
      hydrochloride 150 mg modified release capsules of Ranbaxy and EFEXOR(r)-XR 150 mg
      capsules of Wyeth, in healthy, adult, male, human subjects under fasting
      condition was performed to conclude bioequivalence. Venlafaxine and its major
      active metabolite O-desmethylvenlafaxine (ODV) are racemates. The "(S)-(+)" and
      "(R)-(-)" enantiomers of venlafaxine and ODV are established as being active.
      Hence, subject samples were analyzed using nonstereoselective and stereoselective
      assay methods. Both (S)-(+) and (R)-(-) enantiomers of venlafaxine and ODV showed
      similar absorption and disposition. The 90% confidence intervals for venlafaxine,
      (R)-(-)-venlafaxine as well as (S)-(+)-venlafaxine were within acceptance range
      concluding bioequivalence. The results obtained by stereoselective assay were
      comparable to the nonstereoselective analysis, as sum of concentrations of (S)
      (+)- and (R)-(-)-enantiomers of venlafaxine and ODV. The mean (S)-(+)/(R)-(-)
      ratios of the enantiomers of venlafaxine and ODV at various time points were
      consistent in the study subjects. Therefore, the estimation of venlafaxine and
      ODV using nonstereoselective assay method is effective in distinguishing
      formulation differences (if any) in bioequivalence studies in a cost-effective
      manner.

PMID- 21953856
TI  - Transmission of parental care behavior in African striped mice, Rhabdomys
      Pumilio.
AB  - The expression of behavior, including parental care behavior, is influenced by
      complex interactions of the genes of an organism and the prevailing environmental
      conditions. Previously, we showed that the development of paternal, but not
      maternal, care in the African striped mouse, Rhabdomys pumilio, has a significant
      nongenetic maternal component. Here, we investigate the genetic component of
      parental care behavior from parents to offspring. We first measured the duration
      of parental care behavior of mothers and fathers every second day for 11 days
      postnatally. Subsequently, one son and one daughter from each of these litters
      were paired with unrelated mates when they were adults and their parental care
      behavior scored. Using regression models, we then compared parental care behavior
      of parents and their adult offspring. The transmission of parental care behavior
      from striped mouse fathers to sons and from mothers to both sons and daughters
      did not indicate a genetic component. Instead, we found a patrilineal genetic
      component for parental care in daughters. The reason for this unusual pattern of
      inheritance is not known, but this finding complements that of our other studies,
      showing that the expression of maternal care behavior in adult daughters is also
      not nongenetically influenced by their mothers. We suggest that, although females
      are constrained to provide maternal care in different social contexts, maternal
      care behavior may be influenced genetically by the father.

PMID- 21953855
TI  - Toll-like receptor-7 ligand Imiquimod induces type I interferon and antimicrobial
      peptides to ameliorate dextran sodium sulfate-induced acute colitis.
AB  - BACKGROUND: The pathogenesis of inflammatory bowel disease (IBD) is associated
      with a dysregulated mucosal immune response. Certain stimulators of innate
      immunity (CpG DNA or GM-CSF) are reported to be anti-inflammatory in IBD. Toll
      like receptor-7 (TLR7) is an important regulator of innate immunity and its
      activation plays a key role in induction of type I interferon (IFN). The present
      study tests the hypothesis that the TLR7 agonists Imiquimod has therapeutic
      efficacy in IBD. METHODS: Acute colitis was induced in Balb/c mice by giving 5%
      dextran sodium sulfate (DSS) in drinking water for 7 days. Mice were treated with
      Imiquimod either orally or topically and its therapeutic effects on disease
      activity were examined. Isolated mouse CD11c+ dendritic cells and human
      intestinal epithelial cells (HT29, HCT116) were treated with Imiquimod (10
      MUg/mL) and their susceptibility to intracellular Salmonella typhimurium
      infection was assessed by gentamicin protection assay. RESULTS: Oral
      administration of Imiquimod induced type I IFN expression in the gastrointestinal
      mucosa and ameliorated DSS-induced acute colitis as assessed by clinical
      parameters, histology, and mRNA expression of proinflammatory cytokines. Topical
      administration of Imiquimod also ameliorated DSS colitis by inducing the
      expression of type I IFN in the colonic mucosa. However, no evidence for a
      systemic IFN response was observed. Imiquimod treatments to both CD11c+ and
      intestinal epithelial cells significantly increased expression of antimicrobial
      peptides (AMPs) and reduced survival of intracellular S. typhimurium.
      CONCLUSIONS: Imiquimod induces type I IFN and AMP to ameliorate DSS-induced acute
      colitis and prevents Salmonella survival. Therefore, Imiquimod treatments provide
      a new therapeutic approach for IBD patients.

PMID- 21953857
TI  - The large-scale distribution of somatic mutations in cancer genomes.
AB  - Recently, the genome sequences from several cancers have been published, along
      with the genome from a noncancer tissue from the same individual, allowing the
      identification of new somatic mutations in the cancer. We show that there is
      significant variation in the density of mutations at the 1-Mb scale within three
      cancer genomes and that the density of mutations is correlated between them. We
      also demonstrate that the density of mutations is correlated to that in the
      germline, as measured by the divergence between humans and chimpanzees and humans
      and macaques. We show that the density of mutations is correlated to the guanine
      and cytosine (GC) conent, replication time, distance to telomere and centromere,
      gene density, and nucleosome occupancy in the cancer genomes. However, overall,
      all factors explain less than 40% of the variance in mutation density and each
      factor explains very little of the variance. We find that genes associated with
      cancer occupy regions of the genome with significantly lower mutation rates than
      the average. Finally, we show that the density of mutations varies at a 10-Mb and
      a chromosomal scale, but that the variation at these scales is weak.

PMID- 21953858
TI  - Preoperative assessment of endometrial carcinoma by three-dimensional power
      Doppler angiography.
AB  - OBJECTIVE: Preoperative evaluation of the depth of myometrial invasion in
      endometrial carcinoma is challenging. The objective of this study was to evaluate
      the usefulness of three-dimensional power Doppler angiography (3D-PDA) in this
      setting. METHODS: Sonographic and histological data on 100 consecutive cases of
      endometrial carcinoma were analyzed. The endometrial and myometrial vascular
      indices VI (vascularization index), FI (flow index) and VFI (vascularization flow
      index) were calculated by 3D-PDA. The results were compared with a complete
      surgical staging. RESULTS: The mean ( +/- SD) age of patients was 67.1 +/- 8.8
      (range, 33-87) years. Forty-six patients had deep (>= 50%) myometrial invasion.
      Eight patients had metastases, seven of them with deep invasion. Three patients
      were found to have carcinomas of non-uterine origin on histology, and these were
      excluded from further statistical analysis. The median endometrial and myometrial
      vascular indices were higher in the group with deep invasion than in the group
      without. Following multivariable analysis of the indices only the endometrial FI
      was independently associated with deep invasion (OR, 1.061; 95% CI, 1.023-1.099;
      P = 0.001). However, a greater endometrial volume was also an independent
      predictor of deep invasion (OR, 1.109; 95% CI, 1.011-1.215; P = 0.028).
      CONCLUSION: Our study suggests that endometrial and, to a lesser degree,
      myometrial vascular indices and endometrial volume correlate with the depth of
      myometrial invasion in endometrial carcinoma.

PMID- 21953859
TI  - Self-perception of aging and acute medical events in chronically
      institutionalized middle-aged and older persons with schizophrenia.
AB  - OBJECTIVES: To examine the relationship between self-perceptions of aging and
      acute medical events in chronically institutionalized middle-aged and older
      persons with schizophrenia. METHODS: Participants were 83 persons with
      schizophrenia (30% women; mean age = 58.48, SD = 8.14) residing in a long-stay
      care home, who were without organic mental disorders, mental retardation, serious
      audiovisual impairment, and serious cognitive and physical impairment. They
      received assessments in body mass index, functional health, and global mental
      status, and responded to measures of self-perception of aging at baseline. Acute
      events that required medical attention were recorded for the next 3 months.
      RESULTS: 8% of the participants had acute medical events. Bivariate analysis
      suggested that number of comorbid medical conditions, mobility, Mini-Mental State
      Examination, and negative self-perception of aging were predictive of acute
      medical events. However, multivariate analysis (logistic regression) showed that
      only mobility (OR = 0.78, p = 0.04) and negative self-perception of aging (OR =
      3.38, p = 0.02) had independent effects on acute medical events, with the latter
      being the stronger predictor. Positive aging self-perception, body mass index,
      and smoking were unrelated to medical events. CONCLUSIONS: Physical
      vulnerabilities may not be sufficient to explain the development of acute medical
      events in late-life schizophrenia. How individuals perceive their aging process,
      which is expected to regulate health behavior and help-seeking, may be an even
      more important factor. Further research should investigate whether such self
      perceptions, which are probably rooted in stereotypes about aging socialized
      early in life, are modifiable in this population.

PMID- 21953860
TI  - Thrombin-stimulated connective tissue growth factor (CTGF/CCN2) production in
      human buccal mucosal fibroblasts: Inhibition by epigallocatechin-3-gallate.
AB  - BACKGROUND: Connective tissue growth factor (CTGF/CCN2) is associated with many
      human fibrotic disorders and was found to overexpress in oral submucous fibrosis
      (OSF). OSF is the result of persistent chemical irritation and microtrauma to
      oral mucosa from areca nut. Microtrauma could lead to the release of thrombin.
      METHODS: Thrombin-induced CCN2 expression and its signaling pathways were
      assessed by Western blot analyses in human buccal mucosal fibroblasts. RESULTS:
      Thrombin stimulated CCN2 synthesis in buccal mucosal fibroblasts via activation
      of protease-activated receptor-1. Pretreatment with antioxidant N-acetyl-L
      cysteine, apoptosis signal-regulating kinase 1 inhibitor thioredoxin, and c-Jun
      NH(2) -terminal kinase inhibitor SP600125 significantly reduced thrombin-induced
      CCN2 synthesis. Epigallocatechin-3-gallate completely inhibited thrombin-induced
      CCN2 synthesis. CONCLUSION: Thrombin produced by microtrauma may contribute to
      the pathogenesis of OSF by up-regulating CCN2 expression. This effect could be
      mediated by protease-activated receptor-1, reactive oxygen species, apoptosis
      signal-regulating kinase 1, and c-Jun NH(2) -terminal kinase pathways and
      prevented by epigallocatechin-3-gallate.

PMID- 21953861
TI  - Towards the next generation of solid oxide fuel cells operating below 600 
      degrees c with chemically stable proton-conducting electrolytes.
AB  - The need for reducing the solid oxide fuel cell (SOFC) operating temperature
      below 600  degrees C is imposed by cost reduction, which is essential for
      widespread SOFC use, but might also disclose new applications. To this aim, high
      temperature proton-conducting (HTPC) oxides have gained widespread interest as
      electrolyte materials alternative to oxygen-ion conductors. This Progress Report
      describes recent developments in electrolyte, anode, and cathode materials for
      protonic SOFCs, addressing the issue of chemical stability, processability, and
      good power performance below 600  degrees C. Different fabrication methods are
      reported for anode-supported SOFCs, obtained using state-of-the-art, chemically
      stable proton-conducting electrolyte films. Recent findings show significant
      improvements in the power density output of cells based on doped barium zirconate
      electrolytes, pointing out towards the feasibility of the next generation of
      protonic SOFCs, including a good potential for the development of miniaturized
      SOFCs as portable power supplies.

PMID- 21953862
TI  - Effectiveness of and challenges faced by surveillance systems.
AB  - Drug information or surveillance systems have been developed in an attempt to
      measure illicit drug use and predict new trends. In Australia, three systems are
      specifically designed to monitor drug use trends and related harm. These systems
      have their own strengths and weaknesses. This perspective offers a discussion of
      these facets. A series of case studies is used to highlight how surveillance
      systems can be effective in detecting and monitoring trends of use while
      highlighting the challenges these systems face. As indicated by the case study of
      ecstasy, such surveillance systems are effective and can provide unique
      information when a drug is detected and becomes 'established' in the market but
      the methodology of these systems is challenged when new drug classes emerge
      rapidly, as is illustrated by emerging psychotropic substances such as
      mephedrone.

PMID- 21953863
TI  - Association of SNCA with Parkinson: replication in the Harvard NeuroDiscovery
      Center Biomarker Study.
AB  - BACKGROUND: Mutations in the alpha-synuclein gene (SNCA) cause autosomal dominant
      forms of Parkinson's disease, but the substantial risk conferred by this locus to
      the common sporadic disease has only recently emerged from genome-wide
      association studies. METHODS: We genotyped a prioritized noncoding variant in
      SNCA intron 4 in 344 patients with Parkinson's disease and 275 controls from the
      longitudinal Harvard NeuroDiscovery Center Biomarker Study. RESULTS: The common
      minor allele of rs2736990 was associated with elevated disease susceptibility
      (odds ratio, 1.40; P = .0032). CONCLUSIONS: This result increases confidence in
      the notion that in many clinically well-characterized patients, genetic variation
      in SNCA contributes to "sporadic" disease.

PMID- 21953864
TI  - Pyrolo[1,2:4,5]-1,4-dioxopyrazino[1,2:1,6]pyrido[3,4-b]indoles: a group of
      urokinase inhibitors, their synthesis, and stereochemistry-dependent activity.
AB  - Antifibrinolytic agents are required during complex surgeries to decrease
      bleeding; their pro-thrombotic potency and efficacy in causing hemostasis has
      attracted much attention. To discover new inhibitors of urokinase with high
      selectivity for antifibrinolytic effects over pro-thrombotic effects, the 12
      position of (5aS,12S,14aS)- and (5aS,12R,14aS)-5,14-dioxo-1,2,3,5,5a,6,11,
      12,14,14a-decahydro-5H,14H-pyrolo[1,2:4,5]pyrazino[1,2:1,6]pyrido[3,4-b]indoles
      were modified with L-Ala, L-Asp, L-Phe, L-Trp, L-Lys, L-Ser, Gly, and L-Leu to
      provide 16 (5aS,12S,14aS) and (5aS,12R,14aS) derivatives. In a murine bleeding
      model, the (5aS,12S,14aS) derivatives containing L-Ala, L-Asp, L-Phe, and L-Trp
      induced blood coagulation for the treated mice; they also stimulated thrombus
      formation in a rat thrombosis model, but the other derivatives inhibited
      thrombosis. The most potent compound, the L-Asp derivative, showed a good
      therapeutic window: the minimum effective dose for coagulation was <1 nmol kg(
      1), whereas at 10 nmol kg(-1), no pro-thrombotic effect was observed. This type
      of coagulation action was correlated with a mechanism of urokinase inhibition,
      and these results could lead to the discovery of novel urokinase inhibitors.

PMID- 21953865
TI  - Composition-function relations of cartilaginous tissues engineered from
      chondrocytes and mesenchymal stem cells isolated from bone marrow and
      infrapatellar fat pad.
AB  - The objective of this study was to determine the functional properties of
      cartilaginous tissues generated by porcine MSCs isolated from different tissue
      sources, and to compare these properties to those derived from chondrocytes
      (CCs). MSCs were isolated from bone marrow (BM) and infrapatellar fat pad (FP),
      while CCs were harvested from the articular surface of the femoro-patellar joint.
      Culture-expanded CCs and MSCs were encapsulated in agarose hydrogels and cultured
      in the presence of TGFbeta3. Samples were analysed biomechanically, biochemically
      and histologically at days 0, 21 and 42. After 42 days in free swelling culture,
      mean GAG content was 1.50% w/w in CC-seeded constructs, compared to 0.95% w/w in
      FP- and 0.43% w/w in BM-seeded constructs. Total collagen accumulation was
      highest in FP constructs. DNA content increased with time for all the groups. The
      mechanical functionality of cartilaginous tissues engineered using CCs was
      superior to that generated from either source of MSCs. Differences were also
      observed in the spatial distribution of matrix components in tissues engineered
      using CCs and MSCs, which appears to have a strong influence on the apparent
      mechanical properties of the constructs. Therefore, while functional
      cartilaginous tissues can be engineered using MSCs isolated from different
      sources, the spatial composition of these tissues is unlike that generated using
      chondrocytes, suggesting that MSCs and chondrocytes respond differently to the
      regulatory factors present within developing cartilaginous constructs.

PMID- 21953866
TI  - Placenta-derived MSCs are partially immunogenic and less immunomodulatory than
      bone marrow-derived MSCs.
AB  - Over the past few years, mesenchymal stem cells (MSCs) have become of increasing
      interest for use in the field of regenerative medicine. To date, bone marrow (BM)
      has been the main source of MSCs (BM-MSCs) for both experimental and clinical
      studies. However, the use of MSCs derived from BM can be problematic, due to the
      low number of MSCs found in bone marrow aspirates and the invasive procedure
      associated with obtaining them. We aimed to develop a method of obtaining high
      numbers of purified MSCs from placental tissue with minimal expansion and to
      characterize their phenotype and function relative to BM-MSCs. We show here that
      placenta-derived MSCs (PD-MSCs) can be isolated with high numbers from whole
      placental tissue. However, PD-MSCs isolated from whole tissue were often found to
      be a mixed population of both maternal and neonatal cells. The immunological
      properties of PD-MSCs and BM-MSCs were compared. PD-MSCs were found to express
      lower levels of HLA class I and higher levels of PDL-1 and CD1a, compared to BM
      MSCs. HLA-DR became upregulated in PD-MSCs following treatment with IFNgamma,
      whereas BM-MSCs expressed constitutively low levels of HLA-DR. Whilst untreated
      or IFNgamma-treated BM-MSCs were incapable of stimulating T cells, we observed a
      small T cell proliferation in response to the highest concentration of PD-MSCs
      when treated with IFNgamma. It was noted that BM-MSCs were more immunomodulatory
      than PD-MSCs in this study. We therefore suggest that BM-MSCs may be better
      candidates for use in commercial regenerative or transplantation medicine.

PMID- 21953867
TI  - Cell-printing and transfer technology applications for bone defects in mice.
AB  - Bone regeneration therapy based on the delivery of osteogenic factors and/or
      cells has received a lot of attention in recent years since the discovery of
      pluripotent stem cells. We reported previously that the implantation of capillary
      networks engineered ex vivo by the use of cell-printing technology could improve
      blood perfusion. Here, we developed a new substrate prepared by coating glass
      with polyethylene glycol (PEG) to create a non-adhesive surface and subsequent
      photo-lithography to finely tune the adhesive property for efficient cell
      transfer. We examined the cell-transfer efficiency onto amniotic membrane and
      bone regenerative efficiency in murine calvarial bone defect. Cell transfer of
      KUSA-A1 cells (murine osteoblasts) to amniotic membrane was performed for 1 h
      using the substrates. Cell transfer using the substrate facilitated cell
      engraftment onto the amniotic membrane compared to that by direct cell
      inoculation. KUSA-A1 cells transferred onto the amniotic membrane were applied to
      critical-sized calvarial bone defects in mice. Micro-computed tomography (micro
      CT) analysis showed rapid and effective bone formation by the cell-equipped
      amniotic membrane. These results indicate that the cell-printing and transfer
      technology used to create the cell-equipped amniotic membrane was beneficial for
      the cell delivery system. Our findings support the development of a biologically
      stable and effective bone regeneration therapy.

PMID- 21953868
TI  - Molecular profile of osteoprogenitor cells seeded on allograft bone.
AB  - In order to optimize and modulate bone formation it is essential to understand
      the expression patterns of key bone-specific growth factors, as osteoprogenitor
      cells undergo the processes of proliferation, differentiation and maturation.
      This study reports the sequential expression of bone-related growth and
      transcription factors when bone marrow-derived osteoprogenitor cells from C57BL
      mice were cultured on allograft bone discs. Mineralization and osteocalcin
      protein levels were used to track osteogenic differentiation and maturation. Bone
      related growth factors, such as Bmp-2, Bmp-7, Ctnnb-1, Fgf-2, Igf-1, Vegf-a and
      Tgf-beta1, and transcription factors, such as Runx-2 and osteocalcin, were
      examined by enzyme-linked immunosorbent assay (ELISA) and reverse transcription
      polymerase chain reaction (RT-PCR). Total density of mineralized bone was
      significantly increased 7.6 +/- 0.7% in allografts cultured with cells, compared
      with a 0.5 +/- 2.0% increase in the controls without cells (p < 0.01).
      Osteocalcin protein levels peaked at day 4. Protein expression showed peaks of
      BMP-2 and TGF-beta1 on day 2, with VEGF peaking on day 8, and IGF-1 decreasing on
      day 2. mRNA for Pdgf-a peaked on day 2; Bmp-2 on days 4 and 16; Ctnnb-1 on days 8
      and 20; Vegf-a, Fgf-2, Runx-2 and Igf-1 on day 12; Tgf-beta1 on day 16; and Pdgf
      b on day 20. Osteogenic growth factors correlated with Runx-2 and Ctnnb-1,
      whereas a predominant vascular growth factor, Vegf-a, did not follow this
      pattern. Specific bone-related genes and proteins were expressed in a time
      dependent manner when osteoprogenitor cells were cultured on cortico-cancellous
      bone discs in vitro.

PMID- 21953870
TI  - Chondrogenic differentiation of human bone marrow mesenchymal stem cells in
      chitosan-based scaffolds using a flow-perfusion bioreactor.
AB  - Native articular cartilage is subjected to synovial fluid flow during normal
      joint function. Thus, it is believed that the morphogenesis of articular
      cartilage may be positively regulated by the application of similar stimulation
      in vitro. In the present study, the effect of fluid flow over the chondrogenic
      differentiation of human bone marrow-derived mesenchymal stem cells (hBM-MSCs)
      was investigated. We intended to find out whether the shear stress caused by
      perfusion of the medium through the constructs was capable of augmenting the
      differentiation process. Human BMSCs were isolated from bone marrow aspirates and
      were characterized by flow cytometry. After expansion, hBM-MSCs were seeded
      statically onto fibre mesh scaffolds, consisting of a blend of 50:50
      chitosan:poly(butylene terephthalate adipate) (CPBTA). Constructs were cultured
      in a flow-perfusion bioreactor for 28 days, using complete medium for
      chondrogenesis supplemented by TGFbeta3. An enhanced ECM deposition and collagen
      type II production was observed in the bioreactor samples when compared to the
      static controls. Moreover, it was observed that hBM-MSCs, in static cultures,
      take longer to differentiate. ECM accumulation in these samples is lower than in
      the bioreactor sections, and there is a significant difference in the expression
      of collagen type I. We found that the flow-induced shear stress has a beneficial
      effect on the chondrogenic differentiation of hMSCs.

PMID- 21953869
TI  - Human umbilical cord mesenchymal stromal cells in a sandwich approach for
      osteochondral tissue engineering.
AB  - Cell sources and tissue integration between cartilage and bone regions are
      critical to successful osteochondral regeneration. In this study, human umbilical
      cord mesenchymal stromal cells (hUCMSCs), derived from Wharton's jelly, were
      introduced to the field of osteochondral tissue engineering and a new strategy
      for osteochondral integration was developed by sandwiching a layer of cells
      between chondrogenic and osteogenic constructs before suturing them together.
      Specifically, hUCMSCs were cultured in biodegradable poly-L-lactic acid scaffolds
      for 3 weeks in either chondrogenic or osteogenic medium to differentiate cells
      toward cartilage or bone lineages, respectively. A highly concentrated cell
      solution containing undifferentiated hUCMSCs was pasted onto the surface of the
      bone layer at week 3 and the two layers were then sutured together to form an
      osteochondral composite for another 3 week culture period. Chondrogenic and
      osteogenic differentiation was initiated during the first 3 weeks, as evidenced
      by the expression of type II collagen and runt-related transcription factor 2
      genes, respectively, and continued with the increase of extracellular matrix
      during the last 3 weeks. Histological and immunohistochemical staining, such as
      for glycosaminoglycans, type I collagen and calcium, revealed better integration
      and transition of these matrices between two layers in the composite group
      containing sandwiched cells compared to other control composites. These results
      suggest that hUCMSCs may be a suitable cell source for osteochondral
      regeneration, and the strategy of sandwiching cells between two layers may
      facilitate scaffold and tissue integration.

PMID- 21953871
TI  - Effects of different sera on adipose tissue-derived mesenchymal stromal cells.
AB  - Current cell therapy protocols require considerable numbers of mesenchymal
      stromal cells (MSCs), which can be obtained only by in vitro expansion. The most
      important issue is a choice of optimal growth supplements for cell culture.
      Ideally, these should be of known composition, free of animal components and
      allow production of large homogenic populations of MSCs in a considerably short
      period of time. Since this standard has not been achieved to date, we aimed to
      assess the molecular responses of MSCs to different growth supplements commonly
      in use. MSCs were isolated from breast or abdominal adipose tissue and plated
      into DMEM supplemented with one of four different sera: fetal calf serum (FCS),
      pretested fetal calf serum (FCS-Sp), human allogeneic serum (HS) or artificial
      serum substitute (AS). MSCs cultivated with different serum supplements
      demonstrated distinct morphologies, high adipogenic and osteogenic
      differentiation potential and expressed characteristic antigens. Using real-time
      PCR, we found a large increase in PPARgamma and Msx2 gene expression in both
      lines of proliferating MSCs cultivated with AS. We found that MSCs cultivated in
      the presence of different sera had similar global proteomic expression patterns,
      but comparisons of identified proteins revealed most differences in the MSCs
      cultivated with AS. Our results indicate that MSCs cultivated in the presence of
      FCS and HS display similar growth, differentiation, immunophenotypic and
      proteomic properties, while AS induces more profound changes in the physiology of
      MSCs, suggesting that further fundamental studies should be done before its
      introduction into clinical practice.

PMID- 21953872
TI  - Chondrocytes and bone marrow-derived mesenchymal stem cells undergoing
      chondrogenesis in agarose hydrogels of solid and channelled architectures respond
      differentially to dynamic culture conditions.
AB  - The objective of this study was to investigate how a combination of different
      scaffold architectures and rotational culture would influence the functional
      properties of thick cartilaginous tissues engineered using either chondrocytes or
      bone marrow-derived mesenchymal stem cells (BM-MSCs). Expanded porcine
      chondrocytes and BM-MSCs were suspended in 2% agarose and cast in custom-designed
      moulds to produce either regular solid or channelled construct cylinders. The
      study consisted of three seperate experimental arms. First, chondrocyte and BM
      MSC constructs were cultured in free swelling conditions for 9 weeks. Second,
      constructs were subjected to rotational culture for a period of 3 weeks. Finally,
      BM-MSC-seeded constructs were subjected to delayed rotational culture, in which
      constructs were first cultured for 3 weeks in free swelling conditions, followed
      by an additional 3 weeks in rotating culture conditions. Constructs were
      supplemented with TGFbeta3 during the first 3 weeks of all experiments. The
      introduction of channels alone had little effect on the spatial patterns of
      tissue accumulation in either chondrocyte- or BM-MSC-seeded constructs. The two
      cell types responded differentially to rotational culture, resulting in the
      formation of a more homogeneous tissue in chondrocyte-seeded constructs, but
      significantly inhibiting chondrogenesis of BM-MSCs. This inhibition of
      chondrogenesis in response to dynamic culture conditions was not observed if BM
      MSC-seeded constructs were first maintained in free swelling conditions for 3
      weeks prior to rotation. The results of this study demonstrate that bioreactor
      culture conditions that are beneficial for chondrocyte-based cartilage tissue
      engineering may be suboptimal for BM-MSCs.

PMID- 21953874
TI  - Two pathways for pyrrole formation in coumermycin A(1) biosynthesis: the central
      pyrrole moiety is formed from L-threonine.
AB  - Coumermycin A(1) is an aminocoumarin antibiotic produced by Streptomyces
      rishiriensis. It contains three pyrrole rings, that is, two terminal 5-methyl
      pyrrole-2-carboxyl moieties and a central 3-methylpyrrole-2,4-dicarboxylic acid
      moiety. The biosynthesis of the terminal pyrrole moieties has been elucidated
      previously. However, the biosynthetic precursors of the central pyrrole moiety
      have remained unknown, and none of the genes or enzymes involved in its formation
      has been identified. We now show that five genes, contained in a contiguous 4.7
      kb region within the coumermycin biosynthetic gene cluster, are required for the
      biosynthesis of this central pyrrole moiety. Each of these genes was deleted
      individually, resulting in a strong reduction or an abolishment of coumermycin
      production. External feeding of the central pyrrole moiety restored coumermycin
      production. One of these genes shows similarity to L-threonine kinase genes.
      Feeding of [U-(13)C,(15) N]L-threonine and (13)C NMR analysis of the resulting
      compound unequivocally proved that threonine was incorporated intact into the
      central pyrrole (19 % enrichment) to provide the heterocyclic nitrogen as well as
      four of the seven carbons of this moiety. Therefore, this pyrrole is formed via a
      new, hitherto unknown biosynthetic pathway. A hypothesis for the reaction
      sequence leading to the central pyrrole moiety of coumermycin A(1) is presented.

PMID- 21953873
TI  - Using Nazarov electrocyclization to stage chemoselective [1,2]-migrations:
      stereoselective synthesis of functionalized cyclopentenones.

PMID- 21953875
TI  - Antimicrobial antioxidant daucane sesquiterpenes from Ferula hermonis Boiss.
AB  - Seventeen daucane sesquiterpenoid esters, including a new one (4), were isolated
      from the root of Ferula hermonis Boiss. The structures of the isolated compounds
      were elucidated on the basis of spectroscopic evidence and correlated with known
      compounds. The relative stereochemistry of the new compound was determined using
      2D NOESY and the most stable and the lowest energy conformation was determined
      using molecular modelling. The antimicrobial activity was evaluated by
      determination of MIC using the broth microdilution method against six bacterial
      strains and one fungal strain (Pseudomonas aeruginosa PAO1, Escherichia coli,
      Bacillus subtilis ATCC6633, Mycobacterium bovis BCG Pasteur, Mycobacterium
      tuberculosis H37Rv, Staphylococcus aureus ATCC6538 and Candida albicans SC5314).
      There was a significant indication that compounds 15, 16, 17 demonstrated potent
      activity against Gram +ve (S. aureus, B. subtilis), as well as Mycobacterium
      strains M. bovis BCG and M. tuberculosis H37Rv. None of the isolated compounds
      exhibited a significant antifungal activity. In the antioxidant study using the
      DPPH assay method, the highest radical scavenging activity was observed for
      compounds 15, 16, 17.

PMID- 21953876
TI  - Micronucleus assay in buccal smears of breast carcinoma patients.

PMID- 21953877
TI  - Effect of variable-stiffness walking shoes on knee adduction moment, pain, and
      function in subjects with medial compartment knee osteoarthritis after 1 year.
AB  - This study investigated the load-modifying and clinical efficacy of variable
      stiffness shoes after 12 months in subjects with medial compartment knee
      osteoarthritis. Subjects who completed a prior 6-month study were asked to wear
      their assigned constant-stiffness control or variable-stiffness intervention
      shoes during the remainder of the study. Changes in peak knee adduction moment,
      total Western Ontario and McMaster Universities (WOMAC), and WOMAC pain scores
      were assessed. Seventy-nine subjects were enrolled, and 55 completed the trial.
      Using an intention-to-treat analysis, the variable-stiffness shoes reduced the
      within-day peak knee adduction moment (-5.5%, p < 0.001) in the intervention
      subjects, while the constant-stiffness shoes increased the peak knee adduction
      moment in the control subjects (+3.1%, p = 0.015) at the 12-month visit. WOMAC
      pain and total scores for the intervention group were significantly reduced from
      baseline to 12 months (-32%, p = 0.002 and -35%, p = 0.007, respectively). The
      control group had a reduction of 27% in WOMAC pain score (p = 0.04) and no
      significant reduction in total WOMAC score. Reductions in WOMAC pain and total
      scores were similar between groups (p = 0.8 and p = 0.47, respectively). In the
      intervention group, reductions in adduction moment were related to improvements
      in pain and function (R(2)  = 0.11, p = 0.04). Analysis by disease severity
      revealed greater efficacy in adduction moment reduction in the less severe
      intervention group. While the long-term effects of the intervention shoes on pain
      and function did not differ from control, the data suggest wearing the
      intervention shoe reduces the within-day adduction moment after long-term wear,
      and thus should reduce loading on the affected medial compartment of the knee.

PMID- 21953878
TI  - Phase morphology, physical properties, and biodegradation behavior of novel
      PLA/PHBHHx blends.
AB  - In this study, two biodegradable polyesters [i.e., polylactic acid (PLA) and
      poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx)] with complementarity in
      terms of mechanical performance have been combined, and a series of blends with a
      broad range of compositions has been prepared by thermal compounding. The
      evolution of phase morphologies with the variation of compositions has been
      characterized by using Fourier transform infrared spectroscopic imaging together
      with scanning electron microscope analyses. Thermal, mechanical, and
      biodegradation properties of the PLA/PHBHHx blends were systematically
      investigated. Mechanical properties were further analyzed by using theoretical
      models and correlated with the results of the morphology/structure and
      compatibility of the blends. Results indicate that PLA/PHBHHx blends are
      immiscible but can be compatible to some extent at certain compositions (e.g.,
      PLA/PHBHHx (w/w) = 80/20 and 20/80). The physical properties of the blend could
      be fine tuned by adjusting the blend composition.

PMID- 21953880
TI  - Myoanatomy and serotonergic nervous system of plumatellid and fredericellid
      Phylactolaemata (Lophotrochozoa, Ectoprocta).
AB  - The phylogenetic position of the Ectoprocta within the Lophotrochozoa is
      discussed controversially. For gaining more insight into ectoproct relationships
      and comparing it with other potentially related phyla, we analysed the myoanatomy
      and serotonergic nervous system of adult representatives of the Phylactolaemata
      (Plumatella emarginata, Plumatellavaihiriae, Plumatella fungosa, Fredericella
      sultana). The bodywall contains a mesh of circular and longitudinal muscles. On
      its distal end, the orifice possesses a prominent sphincter and continues into
      the vestibular wall, which has longitudinal and circular musculature. The
      tentacle sheath carries mostly longitudinal muscle fibres in Plumatella sp.,
      whereas F. sultana also possesses regular circular muscle fibres. Three groups of
      muscles are associated with the lophophore: 1) Lophophoral arm muscles (missing
      in Fredericella), 2) epistome musculature and 3) tentacle musculature. The
      epistome flap is encompassed by smooth muscle fibres. A few fibres extend
      medially over the ganglion to its proximal floor. Abfrontal tentacle muscles have
      diagonally arranged muscle fibres in their proximal region, whereas the distal
      region is formed by a stack of muscles that resemble an inverted 'V'. Frontal
      tentacle muscles show more variation and either possess one or two bases. The
      digestive tract possesses circular musculature which is striated except at the
      intestine where it is composed of smooth muscle fibres. The serotonergic nervous
      system is concentrated in the cerebral ganglion. From the latter a serotonergic
      nerve extends to each tentacle base. In Plumatella the inner row of tentacles at
      the lophophoral concavity lacks serotonergic nerves. Bodywall musculature is a
      common feature in many lophotrochozoan phyla, but among other filter feeders like
      the Ectoprocta is only present in the 'lophophorate' Phoronida. The longitudinal
      tentacle musculature is reminiscent of the condition found in phoronids and
      brachiopods, but differs to entoproct tentacles. Although this study shows some
      support for the 'Lophophorata', more comparative analyses of possibly related
      phyla are required.

PMID- 21953879
TI  - Finely tuned temperature-controlled cargo release using paraffin-capped
      mesoporous silica nanoparticles.

PMID- 21953881
TI  - Comorbidities in an asthma population 8-29 years old: a study from the Norwegian
      Prescription Database.
AB  - PURPOSE: To examine the occurrence of chronic diseases and antimicrobial
      treatment in an asthma population 8-29 years old, compared with the general
      population. METHODS: In this cross-sectional study, the asthma population was
      identified from the general population (retrieved from a census covering the
      entire Norwegian population) using filled prescriptions on asthma drugs as a
      proxy measure of current asthma. The outcome was excess occurrence of specific
      diseases (comorbidity) among people with asthma, compared with the age-specific
      general population. Diseases were defined by filled prescriptions with specific
      diagnostic codes (International Classification of Primary Care 2nd edition [ICPC
      2] or International Classification of Diseases 10th revision [ICD-10]) during a 1
      year period in the Norwegian Prescription Database. Nine chronic diseases were
      examined: attention deficit/hyperactivity disorder, epilepsy, migraine, mental
      illness, cardiovascular disease, diabetes, autoimmune disorders, gastro
      oesophageal reflux disease (GORD), and allergy. Additionally, antibacterials
      recommended for respiratory tract infections and antivirals were examined
      (defined by Anatomical Therapeutic Chemical codes). Standardized morbidity ratios
      (SMR) for each disease were calculated. RESULTS: Fifty-nine percent of the
      population with asthma had at least one of nine chronic diseases examined,
      compared with 18% in the general population. Few individuals with asthma had more
      than one additional chronic disease (6% of male subjects and 8% of female
      subjects). SMRs were increased for all diseases except diabetes, implying higher
      than expected occurrence of the specific diseases in people with asthma. This
      pattern was observed in both age groups (8-19 and 20-29 years) and genders.
      Allergy and GORD had highest SMR (range 3.2-4.8), whereas the other diseases were
      in the range 1.2-2.5. CONCLUSIONS: An excess occurrence of comorbidities was
      found in the population with asthma. A majority of people with asthma had one
      additional chronic disease, and few had more than one.

PMID- 21953883
TI  - Chromatographic separation and spectroscopic characterization of the E/Z isomers
      of acrivastine.
AB  - A reverse phase high performance liquid chromatography (HPLC) method has been
      developed for the separation of two geometric isomers of Acrivastine using crude
      reaction mixture. The resolution between two isomers was found more than 2.9. The
      geometric isomers have been isolated by preparative HPLC and characterized by
      spectroscopic techniques, such as NMR, infrared, and MS. The developed method has
      been validated for the determination of Z-isomer in Acrivastine. The limit of
      detection and limit of quantification of the Z-isomer were 0.05 and 0.2 MUg/ml,
      respectively. The developed method is precise, linear, accurate, rugged and
      robust for its intended use.

PMID- 21953882
TI  - Salvinorin A has antiinflammatory and antinociceptive effects in experimental
      models of colitis in mice mediated by KOR and CB1 receptors.
AB  - BACKGROUND: Salvinorin A (SA) has a potent inhibitory action on mouse
      gastrointestinal (GI) motility and ion transport, mediated primarily by kappa
      opioid receptors (KOR). The aim of the present study was to characterize possible
      antiinflammatory and antinociceptive effects of SA in the GI tract of mice.
      METHODS: Colonic damage scores and myeloperoxidase activity were determined after
      intraperitoneal (i.p.), intracolonic (i.c.), and oral (p.o.) administration of SA
      using the trinitrobenzene sulfonic acid (TNBS) and dextran sodium sulfate (DSS)
      models of colitis in mice. Additionally, KOR, cannabinoid (CB)1, and CB2 western
      blot analysis of colon samples was performed. The antinociceptive effect of SA
      was examined based on the number of behavioral responses to i.c. instillation of
      mustard oil (MO). RESULTS: The i.p. (3 mg/kg, twice daily) and p.o. (10 mg/kg,
      twice daily) administration of SA significantly attenuated TNBS and DSS colitis
      in mice. The effect of SA was blocked by KOR antagonist nor-binaltorphimine (10
      mg/kg, i.p.). Western blot analysis showed no influence of SA on KOR, CB1, or CB2
      levels. SA (3 mg/kg, i.p. and 10 mg/kg, i.c.) significantly decreased the number
      of pain responses after i.c. instillation of MO in the vehicle- and TNBS-treated
      mice. The antinociceptive action of SA was blocked by KOR and CB1 antagonists.
      The analgesic effect of i.c. SA was more potent in TNBS-treated mice compared to
      controls. CONCLUSIONS: Our results suggest that the drugs based on the structure
      of SA have the potential to become valuable antiinflammatory or analgesic
      therapeutics for the treatment of GI diseases.

PMID- 21953884
TI  - Glyphosate resistance in perennial Sorghum halepense (Johnsongrass), endowed by
      reduced glyphosate translocation and leaf uptake.
AB  - BACKGROUND: In a large cropping area of northern Argentina, Sorghum halepense
      (Johnsongrass) has evolved towards glyphosate resistance. This study aimed to
      determine the molecular and biochemical basis conferring glyphosate resistance in
      this species. Experiments were conducted to assess target EPSPS gene sequences
      and (14)C-glyphosate leaf absorption and translocation to meristematic tissues.
      RESULTS: Individuals of all resistant (R) accessions exhibited significantly less
      glyphosate translocation to root (11% versus 29%) and stem (9% versus 26%)
      meristems when compared with susceptible (S) plants. A notably higher proportion
      of the applied glyphosate remained in the treated leaves of R plants (63%) than
      in the treated leaves of S plants (27%). In addition, individuals of S. halepense
      accession R(2) consistently showed lower glyphosate absorption rates in both
      adaxial (10-20%) and abaxial (20-25%) leaf surfaces compared with S plants. No
      glyphosate resistance endowing mutations in the EPSPS gene at Pro-101-106
      residues were found in any of the evaluated R accessions. CONCLUSION: The results
      of the present investigation indicate that reduced glyphosate translocation to
      meristems is the primary mechanism endowing glyphosate resistance in S. halepense
      from cropping fields in Argentina. To a lesser extent, reduced glyphosate leaf
      uptake has also been shown to be involved in glyphosate-resistant S. halepense.

PMID- 21953885
TI  - The cause of sudden anemia revealed by the blood film.

PMID- 21953886
TI  - Interplay between long- and short-range interactions drives neuritogenesis on
      stiff surfaces.
AB  - Substrate factors such as surface energy distribution can affect cell functions,
      such as neuronal differentiation of PC12 cells. However, the surface effects that
      trigger such cell responses need to be clarified and analyzed. Here we show that
      the total surface tension is not a critical parameter. Self-assembled monolayers
      of alkylsiloxanes on glass were used as culture substrates. By changing the
      nanoscale structure and ordering of the monolayer, we designed surfaces with a
      range of dispersive (gamma(d) ) and nondispersive (gamma(nd) ) potentials, but
      with a similar value for total free-energy (50 <= gamma(d) + gamma(nd) <= 55 mN m
      1). When seeded on surfaces displaying gamma(d) /gamma(nd) <= 3.7, PC12 cells
      underwent low level of neuritogenesis. On surfaces exhibiting gamma(d) /gamma(nd)
      >= 5.4, neurite outgrowth was greatly enhanced and apparent by only 24 h of
      culture in absence of nerve growth-factor treatment. These data indicate how the
      spatial distribution of surface potentials may control neuritogenesis, thus
      providing a new criterion to address nerve regeneration issues on rigid
      biocompatible surfaces.

PMID- 21953887
TI  - Evidence of constitutional MLH1 epimutation associated to transgenerational
      inheritance of cancer susceptibility.
AB  - Constitutional epimutations of DNA mismatch repair (MMR) genes have been recently
      reported as a possible cause of Lynch syndrome. However, little is known about
      their prevalence, the risk of transmission through the germline and the risk for
      carriers to develop cancers. In this study, we evaluated the contribution of
      constitutional epimutations of MMR genes in Lynch syndrome. A cohort of 134
      unrelated Lynch syndrome-suspected patients without MMR germline mutation was
      screened for constitutional epimutations of MLH1 and MSH2 by quantitative
      bisulfite pyrosequencing. Patients were also screened for the presence of EPCAM
      deletions, a possible cause of MSH2 methylation. Tumors from patients with
      constitutional epimutations were extensively analyzed. We identified a
      constitutional MLH1 epimutation in two proband patients. For one of them, we
      report for the first time evidence of transmission to two children who also
      developed early colonic tumors, indicating that constitutional MLH1 epimutations
      are associated to a real risk of transgenerational inheritance of cancer
      susceptibility. Moreover, a somatic BRAF mutation was detected in one affected
      child, indicating that tumors from patients carrying constitutional MLH1
      epimutation can mimic MSI-high sporadic tumors. These findings may have important
      implications for future diagnostic strategies and genetic counseling.

PMID- 21953888
TI  - Condensin engages chromatin.

PMID- 21953890
TI  - Photo-switchable surface topologies in chiral nematic coatings.

PMID- 21953889
TI  - A new residue-nucleotide propensity potential with structural information
      considered for discriminating protein-RNA docking decoys.
AB  - Understanding the key factors that influence the preferences of residue
      nucleotide interactions in specific protein-RNA interactions has remained a
      research focus. We propose an effective approach to derive residue-nucleotide
      propensity potentials through considering both the types of residues and
      nucleotides, and secondary structure information of proteins and RNAs from the
      currently largest nonredundant and nonribosomal protein-RNA interaction database.
      To test the validity of the potentials, we used them to select near-native
      structures from protein-RNA docking poses. The results show that considering
      secondary structure information, especially for RNAs, greatly improves the
      predictive power of pair potentials. The success rate is raised from 50.7 to
      65.5% for the top 2000 structures, and the number of cases in which a near-native
      structure is ranked in top 50 is increased from 7 to 13 out of 17 cases.
      Furthermore, the exclusion of ribosomes from the database contributes 8.3% to the
      success rate. In addition, some very interesting findings follow: (i) the protein
      secondary structure element pi-helix is strongly associated with RNA-binding
      sites; (ii) the nucleotide uracil occurs frequently in the most preferred pairs
      in which the unpaired and non-Watson-Crick paired uracils are predominant, which
      is probably significant in evolution. The new residue-nucleotide potentials can
      be helpful for the progress of protein-RNA docking methods, and for understanding
      the mechanisms of protein-RNA interactions.

PMID- 21953891
TI  - A new automatic algorithm to extract craniofacial measurements from fetal three
      dimensional volumes.
AB  - OBJECTIVES: Three-dimensional (3D) ultrasound is useful in the prenatal
      evaluation of fetal craniofacial structures, particularly as it provides a
      multiplanar view. However, an expert must designate the area of interest and the
      appropriate view, making measurement of fetal structures using 3D ultrasound both
      time-consuming and subjective. In this study we propose an image analysis system
      that measures automatically and precisely the fetal craniofacial structures and
      evaluate its performance in the second trimester of pregnancy using a new 3D
      volume analysis algorithm. METHODS: A universal facial surface template model
      containing the geometric shape information of a fetal craniofacial structure was
      constructed from a fetal phantom. Using the proposed image analysis system we
      fitted this stored template model using a model deformation approach to
      individual fetal 3D facial volumes from 11 mid-trimester fetuses, and extracted
      automatically the following standard measurements: biparietal diameter (BPD),
      occipitofrontal diameter (OFD), interorbital diameter (IOD), bilateral orbital
      diameter (BOD) and distance between vertex and nasion (VN). The same five
      parameters were measured manually by an expert and the results compared. RESULTS:
      Comparison of the algorithm-based automatic measurements with manual measurements
      made by an expert gave correlation coefficients of 0.99 for BPD, 0.98 for OFD,
      0.80 for BOD, 0.83 for IOD and 0.99 for VN. There were no significant differences
      between automatic and manual measurements. CONCLUSION: Our proposed system
      measures precisely the fetal craniofacial structures using 3D ultrasound, making
      it potentially useful for clinical service. This system could also be applied to
      other clinical fields in future testing.

PMID- 21953892
TI  - Amino acid-based reoxidants for aminohydroxylation: application to the
      construction of amino acid-amino alcohol conjugates.

PMID- 21953893
TI  - Nature and frequency of drug-related problems in self-medication (over-the
      counter drugs) in daily community pharmacy practice in Germany.
AB  - PURPOSE: To quantify drug-related problems (DRPs) in self-medication (over-the
      counter [OTC] drug use) identified by community pharmacists (CPs) in Germany at
      the time the drug is dispensed. METHODS: One hundred CPs were asked to document
      100 consecutive customers presenting symptoms or requesting OTC drugs using a
      standardized documentation form. The number of 10,000 encounters seemed
      reasonable to evaluate the set objective. For each encounter, data such as age,
      sex, and first or repeated request and the availability of a patient file in the
      pharmacy including drug history were documented. Furthermore, identified DRPs,
      problem descriptions, and solutions were documented. Data were transcribed
      electronically, coded, checked for validity, and analyzed. RESULTS: In total, 109
      CPs documented 12,567 encounters identifying DRPs in 17.6% of all cases. Four
      indications comprised more than 70% of all DRPs: pain, respiratory,
      gastrointestinal, and skin disorders. Four DRPs were responsible for almost 75%
      of all DRPs identified: self-medication inappropriate (29.7%), requested product
      inappropriate (20.5%), intended duration of drug use too high including abuse
      (17.1%), and wrong dosage (6.8%). If a drug history was available, significantly
      more cases with wrong dosage (p < 0.05) and drug-drug interactions (p < 0.001)
      were detected. All patients with identified DRPs were counseled accordingly.
      Furthermore, the most frequent interventions were referral to a physician (39.5%)
      and switching to a more appropriate drug (28.1%). CONCLUSIONS: In nearly one of
      five encounters, a direct pharmacist-patient interaction about self-medication
      revealed relevant DRPs. Having access to patient files including data on
      prescription and OTC drugs may increase patient safety.

PMID- 21953894
TI  - Morphology of the embryonic and hatchling American alligator ductus arteriosi and
      implications for embryonic cardiovascular shunting.
AB  - The ductus arteriosi (DA) are embryonic blood vessels found in amniotic
      vertebrates that shunt blood away from the pulmonary artery and lungs and toward
      the aorta. Here, we examine changes in morphology of the right and left DA (LDA),
      and right and left aorta (LAo) from embryonic and hatchling alligators. The
      developing alligator has two-patent DA that join the right and LAo. Both DA
      exhibit a muscular phenotype composed of an internal smooth muscle layer (2-4
      cells thick). At hatching, the lumen diameter of both DA decreases as the vessels
      begin to close within the first 12 h of posthatch life. Between day 1 and day 12
      posthatching, the vessel becomes fully occluded with endothelial and smooth
      muscle cells filling the lumen. A number of DA from hatchlings contained blood
      clots along their length. The lumen of the full term alligator DA is reduced in
      comparison with the full term chicken DA. The developing alligator embryo has an
      additional right-to-left shunt pathway in the LAo arising from the right
      ventricle. The embryonic LAo diameter is twice the diameter of either the right
      DA or LDA, providing a lower resistance pathway for blood leaving the right
      ventricle. On the basis of these findings, we propose that the paired DA of the
      embryonic alligator have a reduced role in the embryonic right-to-left shunt of
      blood from the right ventricle when compared with the avian DA.

PMID- 21953895
TI  - Controlling the dimensionality of charge transport in an organic electrochemical
      transistor by capacitive coupling.

PMID- 21953896
TI  - The discovery of compounds that stimulate the activity of kallikrein-related
      peptidase 3 (KLK3).
AB  - Kallikrein-related peptidase 3 (KLK3), also known as prostate-specific antigen
      (PSA), is the most useful biomarker for prostate cancer (PCa). KLK3 is suggested
      to play a role in regulating cancer growth through anti-angiogenic activity in
      vivo and in vitro. This feature, together with its specificity for prostate
      tissue, makes KLK3 an intriguing target for the design of new therapies for PCa.
      3D pharmacophores for KLK3-stimulating compounds were generated based on peptides
      that bind specifically to KLK3 and increase its enzymatic activity. As a result
      of pharmacophore-based virtual screening, four small, drug-like compounds with
      affinity for KLK3 were discovered and validated by capillary differential
      scanning calorimetry. One of the compounds also stimulated the activity of KLK3,
      and is therefore the first published small molecule with such an activity.

PMID- 21953897
TI  - Camptocormia in Japanese patients with Parkinson's disease: a multicenter study.
AB  - OBJECTIVE: The aim of this work was to investigate the prevalence of camptocormia
      and the clinical characteristics of patients with camptocormia in a large
      population of PD patients. BACKGROUND: Although camptocormia has been recognized
      as a prominent phenomenon in PD, the previous epidemiological reports were
      limited, especially in terms of sample size. METHODS: We evaluated 531 PD
      patients (disease duration: 7.0 +/- 5.5 years, mean +/- standard deviation). We
      examined their clinical features and the prevalence of camptocormia. RESULTS:
      Camptocormia was detected in 22 patients (4.1%) and found in patients who were
      older and had more severe motor symptoms and a higher levodopa (L-dopa) dose (P <
      0.05), compared to the patients without camptocormia. Patients with camptocormia
      showed significantly higher frequencies of autonomic symptoms, such as
      constipation and urinary incontinence (P < 0.05). CONCLUSIONS: Camptocormia is
      uncommon in PD and is associated with disease severity, higher L-dopa dose and
      higher frequencies of autonomic symptoms.

PMID- 21953899
TI  - Synthesis, characterization of calcium phosphates/polyurethane composites for
      weight-bearing implants.
AB  - Calcium phosphate (CaP)/polymer composites have been studied as an alternative
      graft material for the treatment of bone defects. In this study, lysine
      triisocyanate-based polyurethane (PUR) composites were synthesized from both
      hydroxyapatite (HA) and beta-tricalcium phosphate (TCP) to reduce the brittleness
      of CaP and increase the bioactivity of the polymer. The mechanical properties and
      in vitro cellular response were investigated for both HA/PUR and TCP/PUR
      composites. The composites were implanted in femoral defects in rats, and in vivo
      bioactivity was evaluated by X-rays, micro-computed tomography (MUCT), and
      histological sections. In biomechanical testing, PUR improved the mechanical
      properties of the CaP, thus rendering it potentially suitable for weight-bearing
      applications. In vitro cell culture studies showed that CaP/PUR composites are
      biocompatible, with beta-TCP enhancing the cell viability and proliferation
      relative to HA. CaP/PUR composites also supported the differentiation of
      osteoblastic cells on the materials. When implanted in rat femoral defects, the
      CaP/PUR composites were biocompatible and osteoconductive with no adverse
      inflammatory response, as evidenced by X-rays, MUCT images, and histological
      sections. Additionally, a histological examination showed evidence of cellular
      infiltration and appositional remodeling. These results suggest that CaP/PUR
      composites could be potentially useful biomaterials for weight-bearing
      orthopaedic implants.

PMID- 21953900
TI  - Soluble transferrin receptor-ferritin index is the most efficient marker for the
      diagnosis of iron deficiency anemia in patients with IBD.

PMID- 21953901
TI  - B-cell lymphoma of the vagina occurring after treatment for classic Hodgkin
      lymphoma: a case report and literature review.
AB  - Malignant lymphomas of the female genital tract are very uncommon, and the
      development of a diffuse large B-cell lymphoma involving the vagina following
      treatment for classic Hodgkin lymphoma is extremely rare. Clinically and
      morphologically, this entity represents a challenge. We herein report such a case
      with liquid-based Pap test and tissue biopsy findings.

PMID- 21953903
TI  - Determination of melamine in milk powder using gas chromatography-high-resolution
      isotope dilution mass spectrometry.
AB  - A GC-high-resolution isotope dilution MS (IDMS) method for the quantification of
      melamine in milk powder is described. The developed technique is compared to the
      LC-IDMS/MS technique, typically used for the determination of melamine in various
      matrices. The accuracy of the GC-high-resolution IDMS method was demonstrated
      when a small degree of equivalence was obtained in a regional comparative study
      involving the determination of melamine in milk powder.

PMID- 21953902
TI  - Predictors of survival and recurrence after temporal bone resection for cancer.
AB  - BACKGROUND: The purpose of this study was to identify factors predictive of
      outcome in patients undergoing temporal bone resection (TBR) for head and neck
      cancer. METHODS: This was a retrospective study of 72 patients undergoing TBR.
      Factors associated with survival and recurrence were identified on multivariable
      regression. RESULTS: Most tumors were epithelial (81%), commonly (69%) involving
      critical structures. Cervical metastases were uncommon (6%). Squamous cell
      carcinoma (SCC) of the external auditory canal carried a high rate of parotid
      invasion (25%) and parotid nodal metastases (43%). The 5-year rate of overall
      survival (OS) was 62%; disease-specific survival (DSS), 70%; recurrence-free
      survival (RFS), 46%. Factors independently associated with outcome on
      multivariable analysis were margin status and extratemporal spread of disease to
      the parotid, mandible, or regional nodes. Recurrence was common (72%) in cT3-4
      tumors. CONCLUSIONS: Margin status and extratemporal disease spread are the
      strongest independent predictors of survival and recurrence. In SCC of the
      external auditory canal, high rates of parotid involvement support adjunctive
      parotidectomy. Risk of recurrence in T3-T4 tumors may support a role for adjuvant
      therapy.

PMID- 21953904
TI  - Effect of thiol functionalization on the hemo-compatibility of PLGA
      nanoparticles.
AB  - In this study, an attempt was made to reduce the interaction of poly(D,L-lactic
      acid/glycolic acid) (PLGA) nanoparticles with the opsonins and phagocytic cells
      upon functionalization with thiol groups. Terminal carboxylic groups in PLGA were
      conjugated to the amino group of cysteine and nanoparticles were prepared by
      solvent evaporation technique. Detailed in vitro investigations were performed on
      PLGA and cysteine modified PLGA (Cys-PLGA) nanoparticles to asses their blood
      compatibility. The effect of these nanoparticles on the release of
      proinflammatory cytokines (IL-1beta, IL-6, and TNF-alpha) from human macrophage
      cells were evaluated. Thiolation was confirmed by fourier transform infrared
      spectroscopy and Ellman's assay; both PLGA and modified nanoparticles had average
      size in the range of 250 nm. Thiolation was an effective strategy in reducing the
      protein adsorption, complement activation, and platelet activation of PLGA
      nanoparticles. PLGA and modified PLGA nanoparticles were compatible with the
      blood cells and no hemolytic effect was detected. Particles were noncytotoxic on
      L929 cells and release of proinflammatory cytokines from macrophage cells was
      rather unaffected with the modification strategy. From these studies, it seems
      that thiolation of particulate delivery system is an interesting approach in
      manipulating the blood-particle interactions and appears to be an effective
      candidate for injectable drug delivery applications.

PMID- 21953905
TI  - Biological activities of xanthatin from Xanthium strumarium leaves.
AB  - The objective of the present work was to evaluate the biological activities of
      the major bioactive compound, xanthatin, and other compounds from Xanthium
      strumarium (Asteraceae) leaves. Inhibition of bloodstream forms of Trypanosoma
      brucei brucei and leukaemia HL-60 cell proliferation was assessed using resazurin
      as a vital stain. Xanthatin was found to be the major and most active compound
      against T. b. brucei with an IC(50) value of 2.63 ug/mL and a selectivity index
      of 20. The possible mode of action of xanthatin was further evaluated. Xanthatin
      showed antiinflammatory activity by inhibiting both PGE(2) synthesis (24%
      inhibition) and 5-lipoxygenase activity (92% inhibition) at concentrations of 100
      ug/mL and 97 ug/mL, respectively. Xanthatin exhibited weak irreversible
      inhibition of parasite specific trypanothione reductase. Unlike xanthatin,
      diminazene aceturate and ethidium bromide showed strong DNA intercalation with
      IC(50) values of 26.04 ug/mL and 44.70 ug/mL, respectively. Substantial induction
      of caspase 3/7 activity in MIA PaCa-2 cells was observed after 6 h of treatment
      with 100 ug/mL of xanthatin. All these data taken together suggest that xanthatin
      exerts its biological activity by inducing apoptosis and inhibiting both PGE(2)
      synthesis and 5-lipoxygenase activity thereby avoiding unwanted inflammation
      commonly observed in diseases such as trypanosomiasis.

PMID- 21953906
TI  - Special issue: the psychology of bipolar disorders.

PMID- 21953907
TI  - A review and synthesis of positive emotion and reward disturbance in bipolar
      disorder.
AB  - Although positive emotion research has begun to flourish, the extremes and
      potential costs of positive emotion remain understudied. This is an ideal
      clinical model for studying the ways in which positive emotions are disrupted in
      bipolar disorder. Bipolar disorder is characterized by extreme bouts of expansive
      and persistent positive feelings. This paper reviews recent experimental studies,
      selectively examining positive emotion, in individuals at risk for, and diagnosed
      with, bipolar disorder. As an extension of this body of work, I present an
      account of positive emotion disturbance in bipolar disorder, referred to as
      positive emotion persistence. Implications are discussed for the study of bipolar
      disorder and positive emotion that follow.

PMID- 21953908
TI  - A comparison of mood-dependent memory in bipolar disorder and normal controls.
AB  - Mood-dependent memory was investigated in a sample of 28 individuals, with a
      diagnosis of bipolar disorder I but not during acute episodes, and 30 non
      clinical controls by using the word lists from Wechsler Memory Scale--Third
      Edition and abstract inkblot recognition. Positive or negative mood induction
      procedures were used prior to and after the stimuli were presented. After either
      the same or contrasting high or low mood inductions, participants attempted to
      recall the word list and performed an inkblot recognition task. Bipolar patients
      were significantly better at the inkblot recognition in the same mood state,
      showing mood-dependent memory. No differences were found in the verbal recall
      task. This study paves the way for further investigation into memory differences
      of this sort in mood disorders.

PMID- 21953909
TI  - Behavioural risk of bipolar disorder in an analogue population: the role of
      cognitive, developmental and interpersonal factors.
AB  - Research to date has identified the contribution of a number of cognitive,
      developmental and interpersonal risk factors in the development of bipolar
      affective disorder. However, further work is needed to understand the mechanisms
      and interactions between these risk factors in relation to bipolar mood
      instability. The aim of this study is to explore the possibility of identifying
      high risk of bipolar disorder through cognitive and interpersonal factors and to
      further expand our knowledge regarding the relationship between such factors. The
      findings from this work demonstrate that when both cognitive and interpersonal
      variables are entered into one model to predict bipolar high risk, direct effects
      are observed for the interpersonal factors, which then have a fully mediational
      effect on the cognitive factors. This work proposes that interpersonal factors
      develop and maintain cognitive risk factors and that future formulations and
      treatment of bipolar disorder need to focus on addressing such interpersonal
      issues.

PMID- 21953910
TI  - Self-report reasons for alcohol use in bipolar disorders: why drink despite the
      potential risks?
AB  - High rates of alcohol use and misuse are commonly reported for bipolar disorder
      (BD) and in many cases, these impact detrimentally on the course and treatment of
      the disorder. Therefore, knowing the reasons individuals with a diagnosis of BD
      give for drinking alcohol is essential for understanding this association and for
      treatment. This paper aimed to systematically review the literature relating to
      self-reported reasons and motives for alcohol use in BD. By using internet-based
      search engines such as PsycINFO and Medline, six relevant studies were identified
      and then quality-assessed using a set of criteria specifically developed for this
      review. Overall, the findings supported the intuitive notion that individuals
      with a diagnosis of BD use alcohol to relieve distressing mood states. However,
      there was evidence of other mood-related and mood--unrelated reasons--e.g.,
      drinking to enhance euphoric mood or to be sociable. These findings are discussed
      in relation to the self-medication hypothesis and cognitive motivational models
      of alcohol use developed in the general population. The quality assessment also
      revealed several limitations including diagnostically heterogeneous samples and
      inconsistencies in measurement between studies, and recommendations for
      addressing these limitations are given.

PMID- 21953911
TI  - Electrophysiological study of the dominant motor innervation to the extensor
      digitorum communis muscle and long head of triceps brachii at posterior divisions
      of brachial plexus.
AB  - BACKGROUND: Restoration of elbow and finger extension function is still
      challenging in management of complete brachial plexus avulsion injury, mainly
      because of fewer available donor nerves for transfer to the radial nerve.
      Selective neurotization could be a potentially alternative for overcoming this
      dilemma. This study was designed to identify the innervation dominance of the
      extensor digitorum communis muscle (EDCM) and long head of the triceps brachii
      (LTB) at the level of division of brachial plexus. METHODS: From February 2008 to
      October 2009, 17 patients with complete brachial plexus avulsion injury underwent
      the procedure of contralateral C7 nerve root transfer. The posterior divisions of
      brachial plexus on the healthy donor side were intraoperatively stimulated and
      the compound muscle action potentials (CMAPs) from the extensor digitorum
      communis muscle and long head of triceps brachii were recorded by an
      electrophysiological device. RESULTS: In 13 out of 17 patients (76.5%), the
      maximal amplitude of CMAP from EDCM was induced by stimulation of the posterior
      division of lower trunk (PDLT). The mean amplitudes of CMAP from EDCM with
      stimulation of the posterior division of upper trunk (PDUT), middle trunk (PDMT),
      and PDLT were 0.64 +/- 0.95, 1.64 +/- 1.56, and 5.32 +/- 4.67 mV (P < 0.05),
      respectively. The maximal amplitude of CMAP from LTB was induced mainly by
      stimulation of the PDMT) and PDLT (6 out of 11 and 5 out of 11 patients). The
      mean amplitudes of CMAP from LTB with stimulation of the PDUT, PDMT, and PDLT
      were 0.15 +/- 0.24, 5.20 +/- 4.27, and 7.48 +/- 9.90 mV, respectively. The
      differences of CMAPs between stimulation of PDUT and other two divisions were
      significant (P < 0.05). CONCLUSIONS: From the electrophysiological point of view,
      this study showed that the PDLT was the major motor division innervating EDCM,
      and the PDMT and PDLT shared the similar proportion of LTB innervation.

PMID- 21953912
TI  - A unified taxonomy for ciliary dyneins.
AB  - The formation and function of eukaryotic cilia/flagella require the action of a
      large array of dynein microtubule motor complexes. Due to genetic, biochemical,
      and microscopic tractability, Chlamydomonas reinhardtii has become the premier
      model system in which to dissect the role of dyneins in flagellar assembly,
      motility, and signaling. Currently, 54 proteins have been described as components
      of various Chlamydomonas flagellar dyneins or as factors required for their
      assembly in the cytoplasm and/or transport into the flagellum; orthologs of
      nearly all these components are present in other ciliated organisms including
      humans. For historical reasons, the nomenclature of these diverse dynein
      components and their corresponding genes, mutant alleles, and orthologs has
      become extraordinarily confusing. Here, we unify Chlamydomonas dynein gene
      nomenclature and establish a systematic classification scheme based on structural
      properties of the encoded proteins. Furthermore, we provide detailed tabulations
      of the various mutant alleles and protein aliases that have been used and
      explicitly define the correspondence with orthologous components in other model
      organisms and humans.

PMID- 21953913
TI  - A semiphysiologically based pharmacokinetic modeling approach to predict the dose
      exposure relationship of an antiparasitic prodrug/active metabolite pair.
AB  - Dose selection during antiparasitic drug development in animal models and humans
      traditionally has relied on correlations between plasma concentrations obtained
      at or below maximally tolerated doses that are efficacious. The objective of this
      study was to improve the understanding of the relationship between dose and
      plasma/tissue exposure of the model antiparasitic agent, pafuramidine, using a
      semiphysiologically based pharmacokinetic (semi-PBPK) modeling approach.
      Preclinical and clinical data generated during the development of pafuramidine, a
      prodrug of the active metabolite, furamidine, were used. A whole-body semi-PBPK
      model for rats was developed based on a whole-liver PBPK model using rat isolated
      perfused liver data. A whole-body semi-PBPK model for humans was developed on the
      basis of the whole-body rat model. Scaling factors were calculated using
      metabolic and transport clearance data generated from rat and human sandwich
      cultured hepatocytes. Both whole-body models described pafuramidine and
      furamidine disposition in plasma and predicted furamidine tissue (liver and
      kidney) exposure and excretion profiles (biliary and renal). The whole-body
      models predicted that the intestine contributes significantly (30-40%) to
      presystemic furamidine formation in both rats and humans. The predicted terminal
      elimination half-life of furamidine in plasma was 3- to 4-fold longer than that
      of pafuramidine in rats (170 versus 47 h) and humans (64 versus 19 h). The dose
      plasma/tissue exposure relationship for the prodrug/active metabolite pair was
      determined using the whole-body models. The human model proposed a dose regimen
      of pafuramidine (40 mg once daily) based on a predefined efficacy-safety index. A
      similar approach could be used to guide dose-ranging studies in humans for next
      in-class compounds.

PMID- 21953914
TI  - CYP3A4-mediated lopinavir bioactivation and its inhibition by ritonavir.
AB  - The combination of lopinavir (LPV) and ritonavir (RTV) is one of the preferred
      regimens for the treatment of HIV infection with confirmed efficacy and
      relatively low toxicity. LPV alone suffers the poor bioavailability due to its
      rapid and extensive metabolism. RTV boosts the plasma concentration of LPV by
      suppressing its metabolism and thus increasing LPV efficacy. In the current
      study, we found that RTV also inhibits LPV bioactivation. LPV bioactivation was
      investigated in human liver microsomes and cDNA-expressed human cytochromes P450.
      Twelve GSH-trapped reactive metabolites of LPV were identified by using a
      metabolomic approach. Semicarbazide-trapped reactive metabolites of LPV were also
      detected. RTV effectively suppressed all pathways of LPV bioactivation via CYP3A4
      inhibition. Our data together with previous reports suggest that LPV plus RTV is
      an ideal combination because RTV not only boosts LPV plasma concentration, but it
      decreases LPV bioactivation.

PMID- 21953915
TI  - In vitro glucuronidation of the antibacterial triclocarban and its oxidative
      metabolites.
AB  - Triclocarban (3,4,4'-trichlorocarbanilide; TCC) is widely used as an
      antibacterial in bar soaps. During use of these soaps, a significant portion of
      TCC is absorbed by humans. For the elimination from the body, glucuronidation
      plays a key role in both biliary and renal clearance. To investigate this
      metabolic pathway, we performed microsomal incubations of TCC and its
      hydroxylated metabolites 2'-OH-TCC, 3'-OH-TCC, and 6-OH-TCC. Using a new liquid
      chromatography-UV-mass spectrometry method, we could show a rapid glucuronidation
      for all OH-TCCs by the uridine-5'-diphosphate-glucuronosyltransferases (UGT)
      present in liver microsomes of humans (HLM), cynomolgus monkeys (CLM), rats
      (RLM), and mice (MLM). Among the tested human UGT isoforms, UGT1A7, UGT1A8, and
      UGT1A9 showed the highest activity for the conjugation of hydroxylated TCC
      metabolites followed by UGT1A1, UGT1A3, and UGT1A10. Due to this broad pattern of
      active UGTs, OH-TCCs can be efficiently glucuronidated in various tissues, as
      shown for microsomes from human kidney (HKM) and intestine (HIM). The major renal
      metabolites in humans, TCC-N-glucuronide and TCC-N'-glucuronide, were formed at
      very low conversion rates (<1%) by microsomal incubations. Low amounts of N
      glucuronides were generated by HLM, HIM, and HKM, as well as by MLM and CLM, but
      not by RLM, according to the observed species specificity of this metabolic
      pathway. Among the human UGT isoforms, only UGT1A9 had activity for the N
      glucuronidation of TCC. These results present an anomaly where in vivo the
      predominant urinary metabolites of TCC are N and N'-glucuronides, but these
      compounds are slowly produced in vitro.

PMID- 21953916
TI  - Methylmercury and selenium speciation in different tissues of beluga whales
      (Delphinapterus leucas) from the western Canadian Arctic.
AB  - Monitoring data have shown that the total monomethylmercury (CH(3) Hg(+) and its
      complexes; collectively referred as MeHg hereafter) concentrations in Arctic
      marine mammals have remained very high in recent decades. Toward a better
      understanding of the metabolic and toxicological implications of these high
      levels of MeHg, we report here on the molecular forms of MeHg in the muscle,
      brain, liver, and kidneys of 10 beluga whales from the western Canadian Arctic.
      In all tissues analyzed, monomethylmercury was found to be dominated by
      methylmercuric cysteinate, a specific form of MeHg believed to be able to
      transport across the blood-brain barrier. Another MeHg-thiol complex,
      methylmercuric glutathionate, was also detected in the muscle and, to a much
      lesser extent, in the liver and brain tissues. Furthermore, a profound inorganic
      Hg peak was detected in the liver and brain tissues, which showed the same
      retention time as a selenium (Se) peak, suggesting the presence of an Hg-Se
      complex, most likely an inorganic Hg complex with a selenoamino acid. These
      results provide the first analytical support that the binding of MeHg with
      glutathione and Se may have protected beluga whales from the toxic effect of high
      concentrations of MeHg in their body.

PMID- 21953917
TI  - Making proteins with unnatural amino acids: the first engineered aminoacyl-tRNA
      synthetase revisited.

PMID- 21953918
TI  - Masked anemia due to cardiac tamponade in a hydropic fetus caused by placental
      chorioangioma.

PMID- 21953919
TI  - Structure and mechanical properties of a pteropod shell consisting of interlocked
      helical aragonite nanofibers.

PMID- 21953922
TI  - Modified N,N'-dicarbazolyl-3,5-benzene as a high triplet energy host material for
      deep-blue phosphorescent organic light-emitting diodes.

PMID- 21953920
TI  - Angioscopy study from a large patient population comparing sirolimus-eluting
      stent with biodegradable versus durable polymer.
AB  - AIMS: This study aimed to compare the neointimal coverage (NIC), subclinical
      thrombus, color of plaque underneath the stent at 9-month after implantation of
      sirolimus-eluting stent (SES) either with durable or with biodegradable polymer
      (BDPM). METHODS: A total of 175 patients were assigned as Cypher (n = 81, 97
      stents with durable polymer) and Excel (n = 94, 112 stents with BDPM) stent at 9
      month after indexed procedure. NIC was classified from grade 0-3. Color of plaque
      was divided into white, light-yellow, yellow, and dark yellow. Thrombus was
      diagnosed as white or red material with cotton-like or ragged appearance.
      Incomplete NIC (grade 0/1) circled by a blush was termed by "inflaming." RESULTS:
      There were significant differences in unstable angina (90.5 vs. 52.4%, P =
      0.015), previous myocardial infarction (33.3 vs. 4.0%, P = 0.045) and left
      ventricular eject fraction (55.2 +/- 7.8 vs. 62.6 +/- 6.3%, P = 0.021) between
      the Excel and Cypher groups. The minimal- and maximal-NIC grades in the Cypher
      group were 0.67 +/- 0.58 and 2.29 +/- 0.46, respectively, when compared with 1.45
      +/- 0.67 (P < 0.001) and 2.64 +/- 0.49 (P = 0.023) in the Excel group. The
      percentage of yellow plaque, thrombus, "inflaming" and NIC grade of 0 in the
      Excel and Cypher groups, respectively, were as follows: 8.0 vs. 26.8% (P =
      0.031), 9.8 vs. 32.9% (P = 0.024), 8.0 vs. 38.1% (P = 0.017), and 38.1 vs. 0% (P
      < 0.001). Of the stents with "inflaming," 63.6% had thrombus when compared with
      20.1% of the non-erosion stents (P < 0.001). Overlapping segments had the lowest
      NIC grades and more "inflaming" demonstrating a significant difference between
      Cypher vs. Excel stents. NIC grade was positively correlated with thrombus.
      CONCLUSIONS: SES with BDPM has improved NIC resulting in less yellow plaque,
      thrombus, and "inflaming." Overlapping segments had the lowest NIC grade and more
      "inflaming."

PMID- 21953923
TI  - Efficient and substrate-specific hydration of nitriles to amides in water by
      using a CeO2 catalyst.

PMID- 21953924
TI  - One-step hydrothermal method to prepare carbon and lanthanum co-doped TiO2
      nanocrystals with exposed {001} facets and their high UV and visible-light
      photocatalytic activity.

PMID- 21953925
TI  - Investigation of the binding of a carbohydrate-mimetic peptide to its
      complementary anticarbohydrate antibody by STD-NMR spectroscopy and molecular
      dynamics simulations.
AB  - Saturation transfer difference (STD)-NMR spectroscopy was used to probe
      experimentally the bioactive solution conformation of the carbohydrate mimic
      MDWNMHAA 1 of the O-polysaccharide of Shigella flexneri Y when bound to its
      complementary antibody, mAb SYA/J6. Molecular dynamics simulations using the
      ZymeCADTM Molecular Dynamics platform were also undertaken to give a more
      accurate picture of the conformational flexibility and the possibilities for
      bound ligand conformations. The ligand topology, or the dynamic epitope, was
      mapped with the CORCEMA-ST (COmplete Relaxation and Conformational Exchange
      Matrix Analysis of Saturation Transfer) program that calculates a total matrix
      analysis of relaxation and exchange effects to generate predicted STD-NMR
      intensities from simulation. The comparison of these predicted STD enhancements
      with experimental data was used to select a representative binding mode. A
      protocol that employed theoretical STD effects calculated at snapshots during the
      entire course of a molecular dynamics (MD) trajectory of the peptide bound to the
      Fv portion of the antibody, and not the averaged atomic positions of receptor
      ligand complexes, was also examined. In addition, the R factor was calculated on
      the basis of STD (fit) to avoid T1 bias, and an effective R factor, R(eff), was
      defined such that if the calculated STD (fit) for proton k was within error of
      the experimental STD (fit) for proton k, then that calculated STD (fit) for
      proton k was not included in the calculation of the R factor. This protocol was
      effective in deriving the antibody-bound solution conformation of the peptide
      which also differed from the bound conformation determined by X-ray
      crystallography; however, several discrepancies between experimental and
      calculated STD (fit) values were observed. The bound conformation was therefore
      further refined with a simulated annealing refinement protocol known as STD-NMR
      intensity-restrained CORCEMA optimization (SICO) to give a more accurate
      representation of the bound peptide epitope. Further optimization was required in
      this case, but a satisfactory correlation between experimental and calculated STD
      values was obtained. Attempts were also made to obtain STD enhancements with a
      synthetic pentasaccharide hapten, corresponding to the O-polysaccharide, while
      bound to the antibody. However, unfavorable kinetics of binding in this system
      prevented sufficient STD build-up, which, in turn, hindered a rigorous analysis
      via full STD build-up curves.

PMID- 21953926
TI  - Efficient complexation of pyrrole-bridged dizinc(II) bisporphyrin with
      fluorescent probe pyrene: synthesis, structure, and photoinduced singlet-singlet
      energy transfer.
AB  - A diethylpyrrole-bridged dizinc(II) bisporphyrin (Zn(2)DEP) is reported that
      encapsulates fluorescent probe pyrene molecules through strong pi-pi
      interactions, which can relay information about the chemical environment in the
      interior of the host-guest supramolecular assembly. X-ray structures of both
      Zn(2)DEP and the encapsulated pyrene complex are reported, which provides a rare
      opportunity to investigate the structural changes upon guest binding. A
      comparative structural analysis demonstrated the exceptional ability of this
      bisporphyrin platform to open its binding pocket for pyrene encapsulation by a
      vertical displacement of more than 2.45 A, although both Zn(2)DEP and the pyrene
      complex have nearly parallel porphyrin ring orientations. The (1)H NMR spectrum
      of the encapsulated pyrene complex in solution shows the upfield shifts of the
      pyrene protons due to a strong ring current effect, which demonstrates the
      retention of the solid-state structure in solution. To further assess the extent
      to which pyrene guests remain encapsulated in solution, a known fluorescence
      quencher, dimethylaniline, was added to the host-guest assembly, which shows no
      exciplex formation for days in nonpolar solvents. Thus, the assembly also
      retained the structural integrity in solution for a long time. The association
      constant (K(asso)) for such a complexation process in solution was observed to be
      1.78*10(5) M(-2) for 1:2 binding. Steady-state fluorescence and lifetime studies
      indicate significant photoinduced singlet-singlet energy transformation from the
      excited state of pyrene to zinc bisporphyrin.

PMID- 21953927
TI  - Pyrene-containing peptide-based fluorescent organogels: inclusion of graphene
      into the organogel.
AB  - The N-terminally pyrene-conjugated oligopeptide, Py-Phe-Phe-Ala-OMe, (Py=pyrene 1
      butyryl acyl) forms transparent, stable, supramolecular fluorescent organogels in
      various organic solvents. One of these organogels was thoroughly studied using
      various techniques including transmission electron microscopy (TEM), field
      emission scanning electron microscopy (FESEM), atomic force microscopy (AFM),
      Fourier-transform infrared (FTIR) spectroscopy, photoluminescence (PL)
      spectroscopy, and rheology. Unfunctionalized and non-oxidized graphene was
      successfully incorporated into this fluorescent organogel in o-dichlorobenzene
      (ODCB) to form a stable hybrid organogel. Graphene is well dispersed into the gel
      medium by using non-covalent pi-pi stacking interactions with the pyrene
      conjugated gelator peptide. In the presence of graphene, the minimum gelation
      concentration (mgc) of the hybrid organogel was lowered significantly. This
      suggests that there is a favorable interaction between the graphene and the
      gelator peptide within the hybrid organogel system. This hybrid organogel was
      characterized using TEM, AFM, FTIR, PL, and rheological studies. The TEM study of
      graphene-containing hybrid organogel revealed the presence of both graphene
      sheets and entangled gel nanofibers. The AFM study indicated the presence of 3 to
      4 layers in exfoliated graphene in ODCB and the presence of both graphene
      nanosheets and the network of gel nanofibers in the hybrid gel system. The
      rheological investigation suggested that the flow of the hybrid organogel had
      become more resistant towards the applied angular frequency upon the
      incorporation of graphene into the organogel. The hybrid gel is about seven times
      more rigid than that of the native gel.

PMID- 21953928
TI  - A unique case of oxidative addition of interhalogens IX (X=Cl, Br) to
      organodiselone ligands: nature of the chemical bonding in asymmetric I-Se-X
      polarised hypervalent systems.
AB  - The reactivity of the imidazoline-2-selone derivatives 1,1'-methylenebis(3-methyl
      4-imidazoline-2-selone) (D1) and 1,2-ethylenebis(3-methyl-4-imidazoline-2-selone)
      (D2) towards the interhalogens IBr and ICl has been investigated in the solid
      state with the aim of synthesising "T-shaped" hypervalent chalcogen compounds
      featuring the extremely rare linear asymmetric I-E-X moieties (E=S, Se; X=Br,
      Cl). X-ray diffraction analysis and FT-Raman measurements provided a clear
      indication of the presence in the compounds obtained of discrete molecular
      adducts containing I-Se-Br and I-Se-Cl hypervalent moieties following a unique
      oxidative addition of interhalogens IX (X=Cl, Br) to the organoselone ligands. In
      all asymmetric hypervalent systems isolated, a strong polarisation was observed,
      with longer bond lengths at the selenium atom involving the most electronegative
      halogen. A topological electron density analysis on model compounds based on the
      quantum theory of atoms-in-molecules (QTAIM) and electron localisation function
      (ELF) established the three-centre-four-electron (3c-4e) nature of the bonding in
      these very polarised selenium hypervalent systems and new criteria were suggested
      to define and ascertain the hypervalency of the selenium atoms in these and
      related halogen and interhalogen adducts.

PMID- 21953929
TI  - Dopant segregation analysis on Sb:SnO2 nanocrystals.
AB  - The development of reliable nanostructured devices is intrinsically dependent on
      the description and manipulation of materials' properties at the atomic scale.
      Consequently, several technological advances are dependent on improvements in the
      characterization techniques and in the models used to describe the properties of
      nanosized materials as a function of the synthesis parameters. The evaluation of
      doping element distributions in nanocrystals is directly linked to fundamental
      aspects that define the properties of the material, such as surface-energy
      distribution, nanoparticle shape, and crystal growth mechanism. However, this is
      still one of the most challenging tasks in the characterization of materials
      because of the required spatial resolution and other various restrictions from
      quantitative characterization techniques, such as sample degradation and signal
      to-noise ratio. This paper addresses the dopant segregation characterization for
      two antimony-doped tin oxide (Sb:SnO(2)) systems, with different Sb doping
      levels, by the combined use of experimental and simulated high-resolution
      transmission electron microscopy (HRTEM) images and surface-energy ab initio
      calculations. The applied methodology provided three-dimensional models with
      geometrical and compositional information that were demonstrated to be self
      consistent and correspond to the systems' mean properties. The results evidence
      that the dopant distribution configuration is dependent on the system composition
      and that dopant atom redistribution may be an active mechanism for the overall
      surface-energy minimization.

PMID- 21953930
TI  - Dehydrogenation of dodecahydro-N-ethylcarbazole on Pd/Al2O3 model catalysts.
AB  - To elucidate the dehydrogenation mechanism of dodecahydro-N-ethylcarbazole (H(12)
      NEC) on supported Pd catalysts, we have performed a model study under ultra high
      vacuum (UHV) conditions. H(12)-NEC and its final dehydrogenation product, N
      ethylcarbazole (NEC), were deposited by physical vapor deposition (PVD) at
      temperatures between 120 K and 520 K onto a supported model catalyst, which
      consisted of Pd nanoparticles grown on a well-ordered alumina film on NiAl(110).
      Adsorption and thermally induced surface reactions were followed by infrared
      reflection absorption spectroscopy (IRAS) and high-resolution X-ray photoelectron
      spectroscopy (HR-XPS) in combination with density functional theory (DFT)
      calculations. It was shown that, at 120 K, H(12)-NEC adsorbs molecularly both on
      the Al(2)O(3)/NiAl(110) support and on the Pd particles. Initial activation of
      the molecule occurs through C-H bond scission at the 8a- and 9a-positions of the
      carbazole skeleton at temperatures above 170 K. Dehydrogenation successively
      proceeds with increasing temperature. Around 350 K, breakage of one C-N bond
      occurs accompanied by further dehydrogenation of the carbon skeleton. The
      decomposition intermediates reside on the surface up to 500 K. At higher
      temperatures, further decay to small fragments and atomic species is observed.
      These species block most of the absorption sites on the Pd particles, but can be
      oxidatively removed by heating in oxygen at 600 K, fully restoring the original
      adsorption properties of the model catalyst.

PMID- 21953931
TI  - Zinc(II) complexes of ubiquitin: speciation, affinity and binding features.
AB  - Intraneuronal inclusions consisting of hypermetallated, (poly-)ubiquitinated
      proteins are a hallmark of neurodegeneration. To highlight the possible role
      played by metal ions in the dysfunction of the ubiquitin-proteasome system, here
      we report on zinc(II)/ubiquitin binding in terms of affinity constants,
      speciation, preferential binding sites and effects on protein stability and self
      assembly. Potentiometric titrations allowed us to establish that at neutral pH
      only two species, ZnUb and Zn(2)Ub, are present in solution, in line with ESI-MS
      data. A change in the diffusion coefficient of ubiquitin was observed by NMR DOSY
      experiments after addition of Zn(II) ions, and thus indicates metal-promoted
      formation of protein assemblies. Analysis of (1)H, (15)N, (13)Calpha and (13)CO
      chemical-shift perturbation after equimolar addition of Zn(II) ions to ubiquitin
      outlined two different metal-binding modes. The first involves a dynamic
      equilibrium in which zinc(II) is shared between a region including Met1, Gln2,
      Ile3, Phe4, Thr12, Leu15, Glu16, Val17, Glu18, Ile61 and Gln62 residues, which
      represent a site already described for copper binding, and a domain comprising
      Ile23, Glu24, Lys27, Ala28, Gln49, Glu51, Asp52, Arg54 and Thr55 residues. A
      second looser binding mode is centred on His68. Differential scanning calorimetry
      evidenced that addition of increasing amounts of Zn(II) ions does not affect
      protein thermal stability; rather it influences the shape of thermograms because
      of the increased propensity of ubiquitin to self-associate. The results presented
      here indicate that Zn(II) ions may interact with specific regions of ubiquitin
      and promote protein-protein contacts.

PMID- 21953932
TI  - Catalyzed selective direct alpha- and gamma-alkylation of aldehydes with cyclic
      benzyl ethers by using T(+)BF4- in the presence of an inexpensive organic acid or
      anhydride.
AB  - The cross dehydrogenative coupling (CDC) of cyclic benzyl ethers with aliphatic
      and alpha,beta-unsaturated aldehydes has been developed. The mild reaction
      conditions, in which an N-oxoammonium salt derived from TEMPO (2,2,6,6
      tetramethyl-1-piperidinoxyl) is employed as the oxidant in combination with a Cu
      catalyst, allow the use of relatively redox-unstable aldehydes under oxidative
      CDC conditions. The addition of a catalytic amount of trifluoroacetic acid (TFA)
      or Ac(2)O facilitates the reaction and increases the efficiency and selectivity.
      In contrast to the expected alpha-alkylation obtained with aliphatic aldehydes,
      alpha,beta-unsaturated aldehydes led preferentially to the more challenging gamma
      alkylated products. The utility of the developed methodology was demonstrated by
      the synthesis of isochromane-derived bioactive compounds, such as the dopamine
      antagonist sonepiprazole.

PMID- 21953933
TI  - Label-free molecular beacon system based on DNAs containing abasic sites and
      fluorescent ligands that bind abasic sites.
AB  - A new class of label-free molecular beacon (MB) system based on DNA strands that
      contain abasic (AP) sites (AP-DNA) and adopt stem-loop structures, in combination
      with fluorescent ligands that bind these AP sites, has been developed. Unlike a
      conventional MB, which requires covalent labeling of the MB with a fluorophore
      and a quencher, the developed system (APMB) does not require covalent attachment
      of signal transduction units. Detailed sensing functions of a series of APMB
      systems were examined with the aid of the fluorescent ligand named ATMND to
      provide insight into the design strategy for APMB systems. The effects of the
      stem length and the position of the AP site in the stem moiety on the
      fluorescence response of the APMB system were examined. Genotyping of a G/C SNP
      of PCR amplification products was successfully demonstrated with the APMB system
      and blue-fluorescent ATMND as a ligand. The APMB system was further extended to a
      system that utilized green-fluorescent lumiflavin.

PMID- 21953936
TI  - Halochromic phenolate perylene bisimides with unprecedented NIR spectroscopic
      properties.

PMID- 21953937
TI  - Reinforced nanohydroxyapatite/polyamide66 scaffolds by chitosan coating for bone
      tissue engineering.
AB  - High porosity of scaffold is always accompanied by poor mechanical property; the
      aim of this study was to enhance the strength and modulus of the highly porous
      scaffold of nanohydroxyapatite/polyamide66 (n-HA/PA66) by coating chitosan (CS)
      and to investigate the effect of CS content on the scaffold physical properties
      and cytological properties. The results show that CS coating can reinforce the
      scaffold effectively. The compress modulus and strength of the CS coated n
      HA/PA66 scaffolds are improved to 32.71 and 2.38 MPa, respectively, being about
      six times and five times of those of the uncoated scaffolds. Meanwhile, the
      scaffolds still exhibit a highly interconnected porous structure and the porosity
      is approximate about 78%, slightly lower than the value (84%) of uncoated
      scaffold. The cytological properties of scaffolds were also studied in vitro by
      cocultured with osteoblast-like MG63 cells. The cytological experiments
      demonstrate that the reinforced scaffolds display favorable cytocompatibility and
      have no significant difference with the uncoated n-HA/PA66 scaffolds. The CS
      reinforced n-HA/PA66 scaffolds can meet the basic mechanical requirement of bone
      tissue engineering scaffold, presenting a potential for biomedical application in
      bone reconstruction and repair.

PMID- 21953935
TI  - Structural characterization of human Uch37.
AB  - Uch37 is a de-ubiquitylating enzyme that is functionally linked with the 26S
      proteasome via Rpn13, and is essential for metazoan development. Here, we report
      the X-ray crystal structure of full-length human Uch37 at 2.95 A resolution.
      Uch37's catalytic domain is similar to those of all UCH enzymes characterized to
      date. The C-terminal extension is elongated, predominantly helical and contains
      coiled coil interactions. Additionally, we provide an initial characterization of
      Uch37's oligomeric state and identify a systematic error in previous analyses of
      Uch37 activity. Taken together, these data provide a strong foundation for
      further analysis of Uch37's several functions.

PMID- 21953938
TI  - Response to hepatitis A vaccine in children with inflammatory bowel disease
      receiving infliximab.

PMID- 21953939
TI  - Docking analysis and resistance evaluation of clinically relevant mutations
      associated with the HIV-1 non-nucleoside reverse transcriptase inhibitors
      nevirapine, efavirenz and etravirine.
AB  - An integrated computational and statistical approach was used to determine the
      association of non-nucleoside reverse transcriptase inhibitors (NNRTIs)
      nevirapine, efavirenz and etravirine with resistance mutations that cause
      therapeutic failure and their impact on NNRTI resistance. Mutations detected for
      nevirapine virological failure with a prevalence greater than 10% in the used
      patient set were: K103N, Y181C, G190A, and K101E. A support vector regression
      model, based on matched genotypic/phenotypic data (n=850), showed that among 6365
      analyzed mutations, K103N, Y181C and G190A have the first, third, and sixth
      greatest significance for nevirapine resistance, respectively. The most common
      indicator of treatment failure for efavirenz was K103N mutation present in 56.7%
      of the patients where the drug failed, followed by V108I, L100I, and G190A. For
      efavirenz resistance, K103N, G190, and L100I have the first, fourth, and eighth
      greatest significance, respectively, as determined in support vector regression
      model. No positive interactions were observed among nevirapine resistance
      mutations, while a more complex situation was observed with treatment failure of
      efavirenz and etravirine, characterized by the accumulation of multiple
      mutations. Docking simulations and free energy analysis based on docking scores
      of mutated human immunodeficiency virus (HIV) RT complexes were used to evaluate
      the influence of selected mutations on drug recognition. Results from support
      vector regression were confirmed by docking analysis. In particular, for
      nevirapine and efavirenz, a single mutation K103N was associated with the most
      unfavorable energetic profile compared to the wild-type sequence. This is in line
      with recent clinical data reporting that diarylpyrimidine etravirine, a very
      potent third generation drug effective against a wide range of drug-resistant HIV
      1 variants, shows increased affinity towards K103N/S mutants due to its high
      conformational flexibility.

PMID- 21953940
TI  - Carbon materials for chemical capacitive energy storage.
AB  - Carbon materials have attracted intense interests as electrode materials for
      electrochemical capacitors, because of their high surface area, electrical
      conductivity, chemical stability and low cost. Activated carbons produced by
      different activation processes from various precursors are the most widely used
      electrodes. Recently, with the rapid growth of nanotechnology, nanostructured
      electrode materials, such as carbon nanotubes and template-synthesized porous
      carbons have been developed. Their unique electrical properties and well
      controlled pore sizes and structures facilitate fast ion and electron
      transportation. In order to further improve the power and energy densities of the
      capacitors, carbon-based composites combining electrical double layer capacitors
      (EDLC)-capacitance and pseudo-capacitance have been explored. They show not only
      enhanced capacitance, but as well good cyclability. In this review, recent
      progresses on carbon-based electrode materials are summarized, including
      activated carbons, carbon nanotubes, and template-synthesized porous carbons, in
      particular mesoporous carbons. Their advantages and disadvantages as
      electrochemical capacitors are discussed. At the end of this review, the future
      trends of electrochemical capacitors with high energy and power are proposed.

PMID- 21953941
TI  - Generalized dystonia, athetosis, and parkinsonism associated with FOXG1 mutation.

PMID- 21953942
TI  - Cytologic features of sarcomatoid carcinoma of the urinary bladder: a case
      report.
AB  - Sarcomatoid carcinoma of the urinary bladder is a rare entity, whose histogenesis
      and biological behavior remain controversial. The cytological literature on
      sarcomatoid carcinoma in voided urine is very scarce. Clinically, the diagnosis
      of this tumor can be made by computed tomography (CT), magnetic resonance imaging
      (MRI), cytology, and biopsy material. In this study, cytology, histopathology,
      and radiological imaging were employed in order to reach a diagnosis of
      sarcomatoid carcinoma. CT imaging showed increased thickness of the bladder wall
      associated to a polypoid mass. MRI showed a 4-cm sized, broadly necked polypoid
      mass with calcification and ulceration at the right side of the bladder wall.
      T2W1 imaging showed low signal. Voided urinary cytology showed a scattered
      cellular presentation. The tumor cells had a high nucleo- cytoplasmic ratio, with
      elongated cytoplasm with faint with indistinct cytoplasm border. The nucleus was
      oval to round, with large and irregular nucleoli and irregular nuclear membrane.
      These tumor cells were positive for cytokeratin (CKAE1/AE3), vimentin, p53,
      carcinoembryonic antigen (CEA), alpha1-smooth muscle actin (SMA) by the
      immunoperoxidase staining. Histopathology showed spindle-shaped and clumped large
      tumor cells with abundant cytoplasm. Mitotic figures were frequently seen and
      varied from area to area (50% of the tumor cells were positive for MIB1).

PMID- 21953944
TI  - Total or subtotal glossectomy with microsurgical reconstruction: functional and
      oncological results.
AB  - INTRODUCTION: Management of patients after total or subtotal glossectomy presents
      challenging reconstruction of complex three-dimensional defects. Such defects can
      have a dramatic effect on respiration, speech, and nutrition, and may
      significantly impact quality of life. PATIENTS AND METHODS: We present our
      experience with 39 patients submitted to total or subtotal glossectomy and
      reconstruction with microsurgical flaps. Functional results are reported in term
      of swallowing ability, decannulation, and intelligible speech. Oncological
      outcomes are described in terms of local disease control and overall survival
      rate. RESULTS: We carried out 24 total glossectomies and 15 subtotal
      glossectomies. Total glossectomy was associated with a total laryngectomy in
      eight patients. Reconstruction was performed using Taylor's myocutaneous extended
      deep inferior epigastric flap in 33 patients, and an anterolateral thigh
      perforator flap in six patients. A fibula osteocutaneous free flap was raised in
      two patients with an anterior segmental mandibulectomy. A second free flap was
      needed in three cases. Wound complications occurred in 17 patients: an
      orocutaneous fistula in eight patients and a dehiscence of the suture without
      fistulization in nine patients. Oral feeding was resumed in 33 patients (85%). In
      nonlaryngectomized patients, decannulation was achieved in 28 (90%) and speech
      was good or acceptable in 27 (87%). The 5-year adjusted survival for patients
      treated with total or subtotal glossectomy was 47%. CONCLUSION: Our results in a
      relatively large sample of patients who underwent total or subtotal glossectomy
      followed by reconstruction with microsurgical free flaps support the efficacy of
      this surgery as treatment for advanced oral and oral pharyngeal cancers.

PMID- 21953943
TI  - Chemoradiotherapy for maxillary sinus adenoid cystic carcinoma using
      superselective intra-arterial infusion via a superficial temporal artery.
AB  - BACKGROUND: The efficacy of concurrent intra-arterial infusion chemoradiotherapy
      for adenoid cystic carcinoma (ACC) has been described in only a few reports.
      Herein, we report on 2 patients with unresectable ACC of the maxillary sinus
      treated with this approach. METHODS: Patients received concurrent
      chemoradiotherapy. External beam radiation was administered 5 times a week at 2
      Gray (Gy) per fraction for a total of 60 Gy. Chemotherapy consisting of docetaxel
      and cisplatin was administered by superselective intra-arterial infusion via a
      superficial temporal artery. RESULTS: After the completion of all treatments in
      both patients, biopsy specimens of the primary lesions showed complete
      disappearance of all viable and nonviable tumor cells and new bone formation at
      the bony walls of the maxillary sinus. Although complications such as mucositis,
      neutropenia, and anorexia were observed, they were well-tolerated and manageable.
      CONCLUSION: Concurrent chemoradiotherapy using superselective intra-arterial
      infusion is a potential option for patients with unresectable maxillary ACC.

PMID- 21953945
TI  - Unintended consequences of social and economic policies for population health:
      towards a more intentional approach.

PMID- 21953946
TI  - European mental health policy: the key issue is social inclusion.

PMID- 21953948
TI  - Balance measures for propensity score methods: a clinical example on beta-agonist
      use and the risk of myocardial infarction.
AB  - PURPOSE: Propensity score (PS) methods aim to control for confounding by
      balancing confounders between exposed and unexposed subjects with the same PS. PS
      balance measures have been compared in simulated data but limited in empirical
      data. Our objective was to compare balance measures in clinical data and assessed
      the association between long-acting inhalation beta-agonist (LABA) use and
      myocardial infarction. METHODS: We estimated the relationship between LABA use
      and myocardial infarction in a cohort of adults with a diagnosis of asthma or
      chronic obstructive pulmonary disorder from the Utrecht General Practitioner
      Research Network database. More than two thousand PS models, including
      information on the observed confounders age, sex, diabetes, cardiovascular
      disease and chronic obstructive pulmonary disorder status, were applied. The
      balance of these confounders was assessed using the standardised difference (SD),
      Kolmogorov-Smirnov (KS) distance and overlapping coefficient. Correlations
      between these balance measures were calculated. In addition, simulation studies
      were performed to assess the correlation between balance measures and bias.
      RESULTS: LABA use was not related to myocardial infarction after conditioning on
      the PS (median heart rate = 1.14, 95%CI = 0.47-2.75). When using the different
      balance measures for selecting a PS model, similar associations were obtained. In
      our empirical data, SD and KS distance were highly correlated balance measures (r
      = 0.92). In simulations, SD, KS distance and overlapping coefficient were
      similarly correlated to bias (e.g. r = 0.55, r = 0.52 and r = -0.57,
      respectively, when conditioning on the PS). CONCLUSIONS: We recommend using the
      SD or the KS distance to quantify the balance of confounder distributions when
      applying PS methods.

PMID- 21953949
TI  - Gene induction in mature oligodendrocytes with a PLP-tTA mouse line.
AB  - Mature oligodendrocytes are critical for myelin maintenance. To understand the
      molecular basis for this, genetic manipulation of mature oligodendrocytes is
      needed. Here we generated a mature oligodendrocyte tTA (tetracycline-controlled
      transcriptional activator) mouse line which, in combination with a tTA-dependent
      promoter line driving the expression of the desired transgene, can be used for
      gain-of-function studies. We used an oligodendrocyte promoter, the mouse
      proteolipid protein (PLP) promoter, to express mammalianized tTA, and generated a
      PLP-mtTA mouse line. In adults, mtTA mRNA was predominantly detected in brain
      white matter where it co-localized with PLP mRNA. mtTA-mediated gene induction
      was confirmed by crossing to mice with a tTA-dependent promoter driving
      expression of yellow fluorescent protein (tetO-YFP mice). YFP induction in PLP
      mtTA::tetO-YFP mice was consistent with PLP expression in adult mature
      oligodendrocytes and premyelinating-stage myelinating oligodendrocytes. This PLP
      mtTA mouse line is the first to enable gain-of-function studies in mature
      oligodendrocytes with the tet system.

PMID- 21953950
TI  - Liquid Chromatography-Isotope Ratio Mass Spectrometry Users Meeting, November 23
      24, 2010, University of Oxford, UK.

PMID- 21953951
TI  - High-temperature reversed-phase liquid chromatography coupled to isotope ratio
      mass spectrometry.
AB  - Compound-specific isotope analysis (CSIA) by liquid chromatography coupled to
      isotope ratio mass spectrometry (LC/IRMS) has until now been based on ion
      exchange separation. In this work, high-temperature reversed-phase liquid
      chromatography was coupled to, and for the first time carefully evaluated for,
      isotope ratio mass spectrometry (HT-LC/IRMS) with four different stationary
      phases. Under isothermal and temperature gradient conditions, the column bleed of
      XBridge C(18) (up to 180  degrees C), Acquity C(18) (up to 200  degrees C),
      Triart C(18) (up to 150  degrees C), and Zirchrom PBD (up to 150  degrees C) had
      no influence on the precision and accuracy of delta(13) C measurements,
      demonstrating the suitability of these columns for HT-LC/IRMS analysis.
      Increasing the temperature during the LC/IRMS analysis of caffeine on two C(18)
      columns was observed to result in shortened analysis time. The detection limit of
      HT-RPLC/IRMS obtained for caffeine was 30 mg L(-1) (corresponding to 12.4 nmol
      carbon on-column). Temperature-programmed LC/IRMS (i) accomplished complete
      separation of a mixture of caffeine derivatives and a mixture of phenols and (ii)
      did not affect the precision and accuracy of delta(13)C measurements compared
      with flow injection analysis without a column. With temperature-programmed
      LC/IRMS, some compounds that coelute at room temperature could be baseline
      resolved and analyzed for their individual delta(13)C values, leading to an
      important extension of the application range of CSIA.

PMID- 21953952
TI  - Liquid chromatography/isotope ratio mass spectrometry measurement of delta13C of
      amino acids in plant proteins.
AB  - In archaeological studies, the isotopic enrichment values of carbon and nitrogen
      in bone collagen give a degree of information on dietary composition. The
      isotopic enrichments of individual amino acids from bone collagen and dietary
      protein have the potential to provide more precise information about the
      components of diet. A limited amount of work has been done on this, although the
      reliability of these studies is potentially limited by fractionation arising
      through hydrolysis of whole plant tissue (where reaction between amino acids and
      carbohydrates may occur) and, for certain amino acids, the use of derivatives
      (particularly trifluoroacetyl derivatives) for gas chromatography/isotope ratio
      mass spectrometry (GC/IRMS) analysis. The present study takes the approach of
      extracting the protein components of plant tissues before hydrolysis and using
      liquid chromatography/isotope ratio mass spectrometry (LC/IRMS), which does not
      require derivatisation, for measurement of the isotopic enrichment of the amino
      acids. The protocol developed offers a methodology for consistent measurement of
      the delta(13)C values of amino acids, allowing isotopic differences between the
      individual amino acids from different plant tissues to be identified. In
      particular, there are highly significant differences between leaf and seed
      protein amino acids (leaf minus grain) in the cases of threonine (-4.10/00),
      aspartic acid (+3.50/00) and serine (-3.20/00). In addition to its intended
      application in archaeology, the technique will be of value in the fields of plant
      sciences, nutrition and environmental food-web studies.

PMID- 21953953
TI  - The role of liquid chromatography and flow injection analyses coupled to isotope
      ratio mass spectrometry for studying human in vivo glucose metabolism.
AB  - Under most physiological conditions, glucose, or carbohydrate (CHO), homeostasis
      is tightly regulated. In order to mechanistically appraise the origin of
      circulating glucose (e.g. via either gluconeogenesis, glycogenolysis or oral
      glucose intake), and its regulation and oxidation, the use of stable isotope
      tracers is now a well-accepted analytical technique. Methodologically, liquid
      chromatography coupled to isotope ratio mass spectrometry (LC/IRMS) can replace
      gas chromatography coupled to combustion-isotope ratio mass spectrometry
      (GC/C/IRMS) for carrying out compound-specific (13)C isotopic analysis. The
      LC/IRMS approach is well suited for studying glucose metabolism, since the plasma
      glucose concentration is relatively high and the glucose can readily undergo
      chromatography in an aqueous mobile phase. Herewith, we report two main
      methodological approaches in a single instrument: (1) the ability to measure the
      isotopic enrichment of plasma glucose to assess the efficacy of CHO-based
      treatment (cocoa-enriched) during cycling exercise with healthy subjects, and (2)
      the capacity to carry out bulk isotopic analysis of labeled solutions, which is
      generally performed with an elemental analyzer coupled to IRMS. For plasma
      samples measured by LC/IRMS the data show a isotopic precision SD(delta(13)C) and
      SD(APE) of 0.7 0/00 and 0.001, respectively, with delta(13)C and APE values of 
      25.48 0/00 and 0.06, respectively, being generated before and after tracer
      administration. For bulk isotopic measurements, the data show that the presence
      of organic compounds in the blank slightly affects the delta(13)C values. Despite
      some analytical limitations, we clearly demonstrate the usefulness of the LC/IRMS
      especially when (13)C-glucose is required during whole-body human nutritional
      studies.

PMID- 21953954
TI  - Comparison of liquid chromatography-isotope ratio mass spectrometry (LC/IRMS) and
      gas chromatography-combustion-isotope ratio mass spectrometry (GC/C/IRMS) for the
      determination of collagen amino acid delta13C values for palaeodietary and
      palaeoecological reconstruction.
AB  - Results are presented of a comparison of the amino acid (AA) delta(13)C values
      obtained by gas chromatography-combustion-isotope ratio mass spectrometry
      (GC/C/IRMS) and liquid chromatography-isotope ratio mass spectrometry (LC/IRMS).
      Although the primary focus was the compound-specific stable carbon isotope
      analysis of bone collagen AAs, because of its growing application for
      palaeodietary and palaeoecological reconstruction, the results are relevant to
      any field where AA delta(13)C values are required. We compare LC/IRMS with the
      most up-to-date GC/C/IRMS method using N-acetyl methyl ester (NACME) AA
      derivatives. This comparison involves the analysis of standard AAs and
      hydrolysates of archaeological human bone collagen, which have been previously
      investigated as N-trifluoroacetyl isopropyl esters (TFA/IP). It was observed
      that, although GC/C/IRMS analyses required less sample, LC/IRMS permitted the
      analysis of a wider range of AAs, particularly those not amenable to GC analysis
      (e.g. arginine). Accordingly, reconstructed bulk delta(13)C values based on
      LC/IRMS-derived delta(13)C values were closer to the EA/IRMS-derived delta(13)C
      values than those based on GC/C/IRMS values. The analytical errors for LC/IRMS AA
      delta(13)C values were lower than GC/C/IRMS determinations. Inconsistencies in
      the delta(13)C values of the TFA/IP derivatives compared with the NACME- and
      LC/IRMS-derived delta(13)C values suggest inherent problems with the use of
      TFA/IP derivatives, resulting from: (i) inefficient sample combustion, and/or
      (ii) differences in the intra-molecular distribution of delta(13)C values between
      AAs, which are manifested by incomplete combustion. Close similarities between
      the NACME AA delta(13)C values and the LC/IRMS-derived delta(13)C values suggest
      that the TFA/IP derivatives should be abandoned for the natural abundance
      determinations of AA delta(13)C values.

PMID- 21953955
TI  - Liquid chromatography/mass spectrometry stable isotope analysis of dissolved
      organic carbon in stream and soil waters.
AB  - A commercial interface coupling liquid chromatography (LC) to a continuous-flow
      isotope ratio mass spectrometry (CF-IRMS) instrument was used to determine the
      delta(13) C of dissolved organic carbon (DOC) in natural waters. Stream and soil
      waters from a farmland plot in a hedgerow landscape were studied. Based on wet
      chemical oxidation of dissolved organics the LC/IRMS interface allows the on-line
      injection of small volumes of water samples, an oxidation reaction to produce
      CO(2) and gas transfer to the isotope ratio mass spectrometer. In flow injection
      analysis (FIA) mode, bulk DOC delta(13)C analysis was performed on aqueous
      samples of up to 100 MUL in volume in the range of DOC concentration in fresh
      waters (1-10 mg C.L(-1)). Mapping the DOC delta(13)C spatial distribution at the
      plot scale was made possible by this fairly quick method (10 min for triplicate
      analyses) with little sample manipulation. The relative contributions of
      different plot sectors to the DOC pool in the stream draining the plot were
      tentatively inferred on the basis of delta(13)C differences between the
      hydrophilic and hydrophobic components.

PMID- 21953956
TI  - Review: Current applications and challenges for liquid chromatography coupled to
      isotope ratio mass spectrometry (LC/IRMS).
AB  - High-precision isotope analysis is recognized as an essential research tool in
      many fields of study. Until recently, continuous flow isotope ratio mass
      spectrometry (CF-IRMS) was available via an elemental analyzer or a gas
      chromatography inlet system for compound-specific analysis of light stable
      isotopes. In 2004, however, an interface that coupled liquid chromatography with
      IRMS (LC/IRMS) became commercially available for the first time. This brought the
      capability for new areas of application, in particular enabling compound-specific
      delta(13)C analysis of non-volatile, aqueous soluble, compounds from complex
      mixtures. The interface design brought with it several analytical constraints,
      however, in particular a lack of compatibility with certain types of
      chromatography as well as limited flow rates and mobile phase compositions.
      Routine LC/IRMS methods have, however, been established for measuring the
      delta(13)C isotopic ratios of underivatized individual compounds for application
      in archeology, nutrition and physiology, geochemistry, hydrology, soil science
      and food authenticity. Seven years after its introduction, we review the
      technical advances and constraints, methodological developments and new
      applications of liquid chromatography coupled to isotope ratio mass spectrometry.

PMID- 21953957
TI  - High-resolution chromatography/time-of-flight MSE with in silico data mining is
      an information-rich approach to reactive metabolite screening.
AB  - Electrophilic reactive metabolite screening by liquid chromatography/mass
      spectrometry (LC/MS) is commonly performed during drug discovery and early-stage
      drug development. Accurate mass spectrometry has excellent utility in this
      application, but sophisticated data processing strategies are essential to
      extract useful information. Herein, a unified approach to glutathione (GSH)
      trapped reactive metabolite screening with high-resolution LC/TOF MS(E) analysis
      and drug-conjugate-specific in silico data processing was applied to rapid
      analysis of test compounds without the need for stable- or radio-isotope-labeled
      trapping agents. Accurate mass defect filtering (MDF) with a C-heteroatom
      dealkylation algorithm dynamic with mass range was compared to linear MDF and
      shown to minimize false positive results. MS(E) data-filtering, time-alignment
      and data mining post-acquisition enabled detection of 53 GSH conjugates overall
      formed from 5 drugs. Automated comparison of sample and control data in
      conjunction with the mass defect filter enabled detection of several conjugates
      that were not evident with mass defect filtering alone. High- and low-energy
      MS(E) data were time-aligned to generate in silico product ion spectra which were
      successfully applied to structural elucidation of detected GSH conjugates. Pseudo
      neutral loss and precursor ion chromatograms derived post-acquisition
      demonstrated 50.9% potential coverage, at best, of the detected conjugates by any
      individual precursor or neutral loss scan type. In contrast with commonly applied
      neutral loss and precursor-based techniques, the unified method has the advantage
      of applicability across different classes of GSH conjugates. The unified method
      was also successfully applied to cyanide trapping analysis and has potential for
      application to alternate trapping agents.

PMID- 21953958
TI  - An inexpensive, fast, and reliable method for vacuum extraction of soil and plant
      water for stable isotope analyses by mass spectrometry.
AB  - The stable isotopes of water (hydrogen and oxygen isotopes) are of utmost
      interest in ecology and the geosciences. In many cases water has to be extracted
      directly from a matrix such as soil or plant tissue before isotopes can be
      analyzed by mass spectrometry. Currently, the most widely used technique for
      water is cryogenic vacuum extraction. We present a simple and inexpensive
      modification of this method and document tests conducted with soils of various
      grain size and tree core replicates taken on four occasions during 2010. The
      accuracies for sandy soils are between 0.40/00 and 30/00 over a range of 210/00
      and 1650/00 for delta(18)O and delta(2)H, respectively. Spiking tests with water
      of known isotope composition were conducted with soil and tree core samples; they
      indicate reliable precision after an extraction time of 15 min for sandy soils.
      For clayey soils and tree cores, the deviations were up to 0.630/00 and 4.70/00
      for delta(18)O and delta(2)H, respectively. This indicates either that the
      extraction time should be extended or that mechanisms different from Rayleigh
      fractionation play a role. The modified protocol allows a fast and reliable
      extraction of large numbers of water samples from soil and plant material in
      preparation for stable isotope analyses.

PMID- 21953959
TI  - The use of a triple quadrupole linear ion trap mass spectrometer with
      electrospray ionisation for fragmentation studies of selected antifungal drugs.
AB  - Fragmentation studies of three antifungal drugs, clotrimazole, fluconazole and
      clioquinol ,were performed. A triple quadrupole linear ion trap mass spectrometer
      was used for this purpose. This type of equipment enables MS(3) spectra to be
      obtained which lead to better understanding of fragmentation pathways.
      Nevertheless, it is rarely used for fragmentation studies. The results obtained
      here for the antifungal drugs gave further insight into fragmentation pathways of
      clotrimazole and fluconazole. Moreover, fragmentation of clioquinol was
      investigated which had not been presented before.

PMID- 21953960
TI  - A new isolation procedure of nitrate from freshwater for nitrogen and oxygen
      isotope analysis.
AB  - The nitrogen (delta(15)N) and oxygen isotope (delta(18)O) analysis of nitrate
      (NO(3)(-)) from aqueous samples can be used to determine nitrate sources and to
      study N transformation processes. For these purposes, several methods have been
      developed; however, none of them allows an accurate, fast and inexpensive
      analysis. Here, we present a new simple method for the isolation of nitrate,
      which is based on the different solubilities of inorganic salts in an
      acetone/hexane/water mixture. In this solvent, all major nitrate salts are
      soluble, whereas all other oxygen-bearing compounds such as most inorganic
      carbonates, sulfates, and phosphates are not. Nitrate is first concentrated by
      freeze-drying, dissolved in the ternary solvent and separated from insoluble
      compounds by centrifugation. Anhydrous barium nitrate is then precipitated in the
      supernatant solution by adding barium iodide. For delta(18)O analysis, dried
      Ba(NO(3))(2) samples are directly reduced in a high-temperature conversion system
      to CO and measured on-line using isotope ratio mass spectrometry (IRMS). For
      delta(15)N analysis, samples are combusted in an elemental analyzer (EA) coupled
      to an IRMS system. The method has been tested down to 20 umol NO(3)(-) with a
      reproducibility (1SD) of 0.10/00 for nitrogen and 0.2-0.40/00 for oxygen
      isotopes. For nitrogen we observed a small consistent (15) N enrichment of
      +0.20/00, probably due to an incomplete precipitation process and, for oxygen, a
      correction for the incorporation of water in the precipitated Ba(NO(3))(2) has to
      be applied. Apart from being robust, this method is highly efficient and low in
      cost.

PMID- 21953962
TI  - Detailed assessment of isotope ratio infrared spectroscopy and isotope ratio mass
      spectrometry for the stable isotope analysis of plant and soil waters.
AB  - As an alternative to isotope ratio mass spectrometry (IRMS), the isotope ratio
      infrared spectroscopy (IRIS) approach has the advantage of low cost, continuous
      measurement and the capacity for field-based application for the analysis of the
      stable isotopes of water. Recent studies have indicated that there are potential
      issues of organic contamination of the spectral signal in the IRIS method,
      resulting in incorrect results for leaf samples. To gain a more thorough
      understanding of the effects of sample type (e.g., leaf, root, stem and soil),
      sample species, sampling time and climatic condition (dry vs. wet) on water
      isotope estimates using IRIS, we collected soil samples and plant components from
      a number of major species at a fine temporal resolution (every 2 h for 24-48 h)
      across three locations with different climatic conditions in the Heihe River
      Basin, China. The hydrogen and oxygen isotopic compositions of the extracted
      water from these samples were measured using both an IRMS and an IRIS instrument.
      The results show that the mean discrepancies between the IRMS and IRIS approaches
      for delta(18) O and deltaD, respectively, were: -5.60/00 and -75.70/00 for leaf
      water; -4.00/00 and -23.30/00 for stem water; -3.40/00 and -28.20/00 for root
      water; -0.50/00 and -6.70/00 for xylem water; -0.060/00 and -0.30/00 for xylem
      flow; and -0.10/00 and 0.30/00 for soil water. The order of the discrepancy was:
      leaf > stem ~ root > xylem > xylem flow ~ soil. In general, species of the same
      functional types (e.g., woody vs. herbaceous) within similar habitats showed
      similar deviations. For different functional types, the differences were large.
      Sampling at nighttime did not remove the observed deviations.

PMID- 21953961
TI  - Assessment of intracellular methotrexate and methotrexate-polyglutamate
      metabolite concentrations in erythrocytes by ultrafast matrix-assisted laser
      desorption/ionization triple quadrupole tandem mass spectrometry.
AB  - A new ultrafast quantitative and high-throughput mass spectrometric method using
      matrix-assisted laser desorption/ionization triple quadrupole tandem mass
      spectrometry has been developed and validated for determination of intracellular
      erythrocyte concentrations of the antifolate drug methotrexate (MTX) and its
      polyglutamate metabolites. The method consists of a solid-phase extraction of MTX
      and MTX-polyglutamate metabolites from deproteinized erythrocyte lysates spiked
      with aminopterin as internal standard. The newly developed method was validated
      according to the most recent FDA guidelines on linearity, recovery, within-run
      and between-run accuracy and precision and stability of the analytes. The low
      limit of quantification (LLOQ) was 10 nmol/L for all analytes while the limit of
      detection (LOD) determined at a signal-to-noise (S/N) ratio = 3:1 in drug- free
      erythrocyte lysate was on average 0.3 nmol/L. After validation, the new method
      was used in the measurement of intracellular erythrocyte concentrations of MTX
      and MTX-polyglutamate metabolites (MTXPG2 to MTXPG7) in packed human erythrocyte
      samples collected from patients with rheumatoid arthritis receiving low-dose oral
      methotrexate therapy. Mean (SD) intracellular erythrocyte concentrations observed
      in patient samples were 12.8 (12.6), 12.4 (9.4), 44.4 (30.0), 33.6 (35.9) and 9.4
      (8.2) nmol/L for MTX to MTXPG5, respectively, in 10(6) erythrocytes. The highest
      observed glutamylation degree of MTX was MTXPG5, the very long chain MTX
      polyglutamate metabolites MTXPG6 and MTXPG7 were not detected in the packed
      erythrocyte pellets collected from rheumatoid arthritis patients.

PMID- 21953963
TI  - The effects of alpha-cellulose extraction and blue-stain fungus on retrospective
      studies of carbon and oxygen isotope variation in live and dead trees.
AB  - Tree-ring carbon and oxygen isotope ratios from live and recently dead trees may
      reveal important mechanisms of tree mortality. However, wood decay in dead trees
      may alter the delta(13)C and delta(18)O values of whole wood obscuring the
      isotopic signal associated with factors leading up to and including physiological
      death. We examined whole sapwood and alpha-cellulose from live and dead specimens
      of ponderosa pine (Pinus ponderosa), one-seed juniper (Juniperous monosperma),
      pinon pine (Pinus edulis) and white fir (Abies concolor), including those with
      fungal growth and beetle frass in the wood, to determine if alpha-cellulose
      extraction is necessary for the accurate interpretation of isotopic compositions
      in the dead trees. We found that the offset between the delta(13)C or delta(18)O
      values of alpha-cellulose and whole wood was the same for both live and dead
      trees across a large range of inter-annual and regional climate differences. The
      method of alpha-cellulose extraction, whether Leavitt-Danzer or Standard Brendel
      modified for small samples, imparts significant differences in the delta(13)C (up
      to 0.40/00) and delta(18) O (up to 1.20/00) of alpha-cellulose, as reported by
      other studies. There was no effect of beetle frass or blue-stain fungus
      (Ophiostoma) on the delta(13)C and delta(18)O of whole wood or alpha-cellulose.
      The relationships between whole wood and alpha-cellulose delta(13)C for
      ponderosa, pinon and juniper yielded slopes of ~1, while the relationship between
      delta(18)O of whole wood and alpha-cellulose was less clear. We conclude that
      there are few analytical or sampling obstacles to retrospective studies of
      isotopic patterns of tree mortality in forests of the western United States.

PMID- 21953964
TI  - The double nature of 1,5-diaminonaphthalene as matrix-assisted laser
      desorption/ionization matrix: some experimental evidence of the protonation and
      reduction mechanisms.
AB  - 1,5-Diaminonaphthalene (DAN) has been described as an interesting and effective
      matrix for matrix-assisted laser desorption/ionization (MALDI) experiments in
      positive ion mode, being able to activate in-source decomposition phenomena and,
      when employed for the analysis of proteins containing disulphide bridge(s), being
      able to activate reduction processes, resulting in disulphide bridge cleavage.
      The mechanisms of the DAN reactivity have been studied in detail, and the results
      indicate that the reduction properties of the matrix are of a radical nature. In
      the present study the structure of the reactive species produced by DAN,
      responsible for its reductive properties, has been investigated by accurate mass
      measurements and tandem mass spectrometry (MS/MS) experiments. Contrary to what
      is usually observed by laser irradiation of other MALDI matrices (with the sole
      formation of the MH(+) ion of the matrix), DAN leads to the formation of odd
      electron molecular ions M(+*) . This can be rationalized by the occurrence of two
      photon pooling processes, due to the low ionization energy of DAN. Thus the M(+*)
      ion of DAN can be considered responsible for both analyte protonation and
      disulphide bond reduction and some mechanisms are proposed for this behaviour.

PMID- 21953965
TI  - Determination of elemental composition of volatile organic compounds from Chinese
      rose oil by spectral accuracy and mass accuracy.
AB  - Elemental composition determination of volatile organic compounds through high
      mass accuracy and isotope pattern matching could not be routinely achieved with a
      unit-mass resolution mass spectrometer until the recent development of the
      comprehensive instrument line-shape calibration technology. Through this unique
      technology, both m/z values and mass spectral peak shapes are calibrated
      simultaneously. Of fundamental importance is that calibrated mass spectra have
      symmetric and mathematically known peak shapes, which makes it possible to
      deconvolute overlapped monoisotopes and their (13)C-isotope peaks and achieve
      accurate mass measurements. The key experimental requirements for the
      measurements are to acquire true raw data in a profile or continuum mode with the
      acquisition threshold set to zero. A total of 13 ions from Chinese rose oil were
      analyzed with internal calibration. Most of the ions produced high mass accuracy
      of better than 5 mDa and high spectral accuracy of better than 99%. These results
      allow five tested ions to be identified with unique elemental compositions and
      the other eight ions to be determined as a top match from multiple candidates
      based on spectral accuracy. One of them, a coeluted component (Nerol) with m/z
      154, could not be identified by conventional GC/MS (gas chromatography/mass
      spectrometry) and library search. Such effective determination for elemental
      compositions of the volatile organic compounds with a unit-mass resolution
      quadrupole system is obviously attributed to the significant improvement of mass
      accuracy. More importantly, high spectral accuracy available through the
      instrument line-shape calibration enables highly accurate isotope pattern
      recognition for unknown identification.

PMID- 21953966
TI  - Use of quadrupole time-of-flight mass spectrometry to determine proposed
      structures of transformation products of the herbicide bromacil after water
      chlorination.
AB  - The herbicide bromacil has been extensively used in the Spanish Mediterranean
      region, and although plant protection products containing bromacil have been
      withdrawn by the European Union, this compound is still frequently detected in
      surface and ground water of this area. However, the fast and complete
      disappearance of this compound has been observed in water intended for human
      consumption, after it has been subjected to chlorination. There is a concern
      about the possible degradation products formed, since they might be present in
      drinking water and might be hazardous. In this work, the sensitive full-spectrum
      acquisition, high resolution and exact mass capabilities of hybrid quadrupole
      time-of-flight (QTOF) mass spectrometry have allowed the discovery and proposal
      of structures of transformation products (TPs) of bromacil in water subjected to
      chlorination. Different ground water samples spiked at 0.5 ug/mL were subjected
      to the conventional chlorination procedure applied to drinking waters, sampling 2
      mL aliquots at different time intervals (1, 10 and 30 min). The corresponding non
      spiked water was used as control sample in each experiment. Afterwards, 50 MUL of
      the water was directly injected into an ultra-high-pressure liquid chromatography
      (UHPLC)/electrospray ionization (ESI)-(Q)TOF system. The QTOF instrument enabled
      the simultaneous recording of two acquisition functions at different collision
      energies (MS(E) approach): the low-energy (LE) function, fixed at 4 eV, and the
      high-energy (HE) function, with a collision energy ramp from 15 to 40 eV. This
      approach enables the simultaneous acquisition of both parent (deprotonated and
      protonated molecules) and fragment ions in a single injection. The low mass
      errors observed for the deprotonated and protonated molecules (detected in LE
      function) allowed the assignment of a highly probable molecular formula. Fragment
      ions and neutral losses were investigated in both LE and HE spectra to elucidate
      the structures of the TPs found. For those compounds that displayed poor
      fragmentation, product ion scan (MS/MS) experiments were also performed. On
      processing the data with specialized software (MetaboLynx), four bromacil TPs
      were detected and their structures were elucidated. To our knowledge, two of them
      had not previously been reported.

PMID- 21953967
TI  - A novel online approach to the determination of isotopic ratios for organically
      bound chlorine, bromine and sulphur.
AB  - A novel approach for the measurement of (37)Cl, (81)Br and (34)S in organic
      compounds containing chlorine, bromine, and sulphur is presented to overcome some
      of the major drawbacks of existing methods. Contemporary methods either require
      reference materials with the exact molecular compositions of the substances to be
      tested, or necessitate several laborious offline procedures prior to isotope
      analysis. In our online setup, organic compounds are separated by gas
      chromatography (GC) coupled to a high-temperature reactor. Using hydrogen as a
      makeup gas, the reactor achieves quantitative conversion of chlorinated,
      brominated and sulphurated organic compounds into gaseous hydrogen chloride
      (HCl), hydrogen bromide (HBr), and hydrogen sulphide (H(2)S), respectively. In
      this study, the GC interface was coupled to a quadrupole mass spectrometer
      operated in single-ion mode. The ion traces of either H(35)Cl (m/z 36) and
      H(37)Cl (m/z 38), H(79)Br (m/z 80) and H(81)Br (m/z 82), or H(2)(32)S (m/z 34)
      and H(2)(34)S (m/z 36), were recorded to determine the isotopic ratios of
      chlorine, bromine, and sulphur isotopes. The conversion interface presented here
      provides a basis for a novel method for compound-specific isotope analysis of
      halogenated and sulphur-containing compounds. Rapid online measurements of
      organic chlorine-, bromine- and sulphur-containing mixtures will facilitate the
      isotopic analysis of compounds containing these elements, and broaden their usage
      in fields of environmental forensics employing isotopic concepts.

PMID- 21953968
TI  - Simultaneous quantitation of testosterone and estradiol in human cell line
      (H295R) by liquid chromatography/positive atmospheric pressure photoionization
      tandem mass spectrometry.
AB  - The possible interaction of environmental contaminants with the endocrine system
      has been an environmental concern since the early 1990s. To examine these
      interactions test guidelines have been introduced by regulatory agencies to
      screen for possible endocrine active compounds. One of these guidelines is the
      EPA's OPPTS 890.1550 [Steroidogenesis (Human Cell Line-H295R)]. This guideline
      requires the quantification of two major biomarkers (testosterone and estradiol)
      in various biological test systems. Traditional quantitation methodologies such
      as Radioimmunoassay (RIA) and Enzyme-linked Immunosorbent Assay (ELISA) have been
      used to quantify low levels of steroids. However, those methodologies have
      drawbacks such as the radioactive safety, antibody availability, separate assay
      for each biomarker, and lack of selectivity. In the current study, a rapid and
      sensitive liquid chromatography/positive atmospheric pressure photoionization
      tandem mass spectrometry method (LC/APPI-MS/MS) has been developed and validated
      for the simultaneous quantitation of testosterone and estradiol in the H295R cell
      line. Briefly, the media from cultured cells was extracted with dichloromethane
      (CH(2)Cl(2)) containing internal standards of both testosterone-d(3) and
      estradiol-(13)C(3); then, the extracted organic layer was concentrated down to
      dryness. The final residue was derivatized with dansyl chloride solution, and
      directly analyzed by LC/APPI-MS/MS. The calibration curves, with concentration
      ranging from 10 to 2500 pg/mL, were linear with coefficient >0.99. The lower
      limits of quantitation for both testosterone and estradiol were 10 pg/mL. This
      method was successfully validated to support requirements of the current EPA
      Steroidogenesis guideline. This type of method may also provide value for rapid
      and precise measurements of these two hormones in other in vitro or in vivo test
      systems.

PMID- 21953969
TI  - Fast screening of highly glycosylated plant sphingolipids by tandem mass
      spectrometry.
AB  - The structural characterization of Glycosyl-Inositol-Phospho-Ceramides (GIPCs),
      which are the main sphingolipids of plant tissues, is a critical step towards the
      understanding of their physiological function. After optimization of their
      extraction, numerous plant GIPCs have been characterized by mass spectrometry.
      Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) full
      scan analysis of negative ions provides a quick overview of GIPC distribution.
      Clear differences were observed for the two plant models studied: six GIPC series
      bearing from two to seven saccharide units were detected in tobacco BY-2 cell
      extracts, whereas GIPCs extracted from A. thaliana cell cultures and leaves were
      less diverse, with a dominance of species containing only two saccharide units.
      The number of GIPC species was around 50 in A. thaliana and 120 in tobacco BY-2
      cells. MALDI-MS/MS spectra gave access to detailed structural information
      relative to the ceramide moiety, the polar head, as well as the number and types
      of saccharide units. Once released from GIPCs, fatty acid chains and long-chain
      bases were analyzed by GC/MS to verify that all GIPC series were taken into
      account by the MALDI-MS/MS approach. ESI-MS/MS provided complementary information
      for the identification of isobaric species and fatty acid chains. Such a
      methodology, mostly relying on MALDI-MS/MS, should open new avenues to determine
      structure-function relationships between glycosphingolipids and membrane
      organization.

PMID- 21953970
TI  - Backtracking the movements of a migratory bird: a case study of a white-fronted
      goose (Anser albifrons).
AB  - The occurrence of avian influenza has brought attention to migrating birds and
      their migratory routes as possible carriers and gates, respectively, of the
      pathogenic influenza virus. There is a need to verify migration routes and to
      back-track the migration routes of infected animals. Stable isotope analysis of
      bird feathers is a valuable tool for studying the migratory pattern of birds, by
      gaining information about the environmental conditions during the growth of the
      feathers. Ideally, if different feathers that have grown during different periods
      are investigated, not only can information about the molting region be extracted,
      but also some clues can be obtained about stop-overs during the migration of
      individual animals, enabling the reconstruction of the pathway. In the presented
      case study the hydrogen, carbon nitrogen and sulfur stable isotope ratios of
      different types of feathers (primaries, down feathers and blood pinfeathers) from
      one white-fronted goose specimen have been determined. These ratios differ
      significantly for some elements. By taking into account the different time of
      growth of the respective feathers, the isotope data can be interpreted with
      respect to the animal migration route from the summer (and molting) to the
      wintering region. This is the first paper to attempt to map the migration pathway
      using different types of feather from a single individual.

PMID- 21953971
TI  - Fragmentation of pentacoordinate spirobicyclic aminoacyl-phosphoranes (P-AAs) by
      electrospray ionization tandem mass spectrometry concerning P-O and P-N bond
      cleavage.
AB  - The fragmentation pathways of both protonated and sodiated pentacoordinate
      spirobicyclic aminoacylphosphoranes (P-AAs) have been studied by electrospray
      ionization multi-stage mass spectrometry (ESI-MS(n)) in positive mode. The
      possible pathways and their mechanisms are elucidated through the combination of
      ESI-MS/MS, isotope ((15)N and (2)H) labeling and high-resolution Fourier
      transform ion cyclotron resonance (FTICR)-MS/MS. The relative Gibbs free energies
      (DeltaG) of the product ions and possible fragmentation pathways are estimated at
      the B3LYP/6-31 G(d) level of theory. The theoretical calculations show that both
      protonated and sodiated P-AAs would quickly fragment before Berry pseudorotation.
      For protonated P-AAs, they have different tendencies to P-O or P-N bond cleavage.
      For sodiated P-AAs, the P-N bond is easier to cleave and produces the
      tetracoordinated phosphorus ion H. These results to some extent may give a clue
      to the chemistry of the active sites of phosphoryl transfer enzymes and will
      enrich the gas-phase ESI-MS ion chemistry of pentacoordinate phosphoranes.

PMID- 21953972
TI  - Preventing false negatives with high-resolution mass spectrometry: the
      benzophenone case.
AB  - Benzophenone (BP) is one of the many contaminants reported as present in
      foodstuffs due to its migration from food packaging materials. Liquid
      chromatography/tandem mass spectrometry (LC/MS/MS) is acknowledged in the
      literature as the method of choice for this analysis. However, cases have been
      reported where the use of this methodology was insufficient to unambiguously
      confirm the presence of a contaminant. In previous work performed by the authors,
      the unequivocal identification of BP in packaged foods was not possible even when
      monitoring two m/z transitions (precursor ion - product ion), since ion ratio
      errors higher than 20% were obtained. In order to overcome this analytical
      problem a fast, sensitive and selective liquid chromatography/high-resolution
      mass spectrometry (LC/HRMS) methodology has been developed and applied to the
      analysis of BP in packaged foods. A direct comparison between LC/HRMS and
      LC/MS/MS data indicated better selectivity when working with LC/HRMS at a
      resolving power of 50,000 FWHM (full width at half maximum) than when monitoring
      two m/z transitions by LC/MS/MS. The resolving power used enabled the detection
      and identification of Harman as the compound impeding the confirmation of BP by
      LC-MS/MS. Similar quantitative results were obtained by an Orbitrap mass analyser
      (ExactiveTM) and a triple quadrupole mass analyser (TSQ Quantum Ultra AMTM).

PMID- 21953973
TI  - Metabolite identification of triptolide by data-dependent accurate mass
      spectrometric analysis in combination with online hydrogen/deuterium exchange and
      multiple data-mining techniques.
AB  - Triptolide (TP), the primary active component of the herbal medicine Tripterygium
      wilfordii Hook F, has shown promising antileukemic and anti-inflammatory
      activity. The pharmacokinetic profile of TP indicates an extensive metabolic
      elimination in vivo; however, its metabolic data is rarely available partly
      because of the difficulty in identifying it due to the absence of appropriate
      ultraviolet chromophores in the structure and the presence of endogenous
      interferences in biological samples. In the present study, the biotransformation
      of TP was investigated by improved data-dependent accurate mass spectrometric
      analysis, using an LTQ/Orbitrap hybrid mass spectrometer in conjunction with the
      online hydrogen (H)/deuterium (D) exchange technique for rapid structural
      characterization. Accurate full-scan MS and MS/MS data were processed with
      multiple post-acquisition data-mining techniques, which were complementary and
      effective in detecting both common and uncommon metabolites from biological
      matrices. As a result, 38 phase I, 9 phase II and 8 N-acetylcysteine (NAC)
      metabolites of TP were found in rat urine. Accurate MS/MS data were used to
      support assignments of metabolite structures, and online H/D exchange experiments
      provided additional evidence for exchangeable hydrogen atoms in the structure.
      The results showed the main phase I metabolic pathways of TP are hydroxylation,
      hydrolysis and desaturation, and the resulting metabolites subsequently undergo
      phase II processes. The presence of NAC conjugates indicated the capability of TP
      to form reactive intermediate species. This study also demonstrated the
      effectiveness of LC/HR-MS(n) in combination with multiple post-acquisition data
      mining methods and the online H/D exchange technique for the rapid identification
      of drug metabolites.

PMID- 21953974
TI  - Considerations for quantification of lipids in nerve tissue using matrix-assisted
      laser desorption/ionization mass spectrometric imaging.
AB  - Matrix-assisted laser desorption/ionization (MALDI) mass spectrometric imaging is
      a technique that provides the ability to identify and characterize endogenous and
      exogenous compounds spatially within tissue with relatively little sample
      preparation. While it is a proven methodology for qualitative analysis, little
      has been reported for its utility in quantitative measurements. In the current
      work, inherent challenges in MALDI quantification are addressed. Signal response
      is monitored over successive analyses of a single tissue section to minimize
      error due to variability in the laser, matrix application, and sample
      inhomogeneity. Methods for the application of an internal standard to tissue
      sections are evaluated and used to quantify endogenous lipids in nerve tissue. A
      precision of 5% or less standard error was achieved, illustrating that MALDI
      imaging offers a reliable means of in situ quantification for microgram-sized
      samples and requires minimal sample preparation.

PMID- 21953975
TI  - Tandem mass spectrometry based investigation of cinnamylideneacetophenone
      derivatives: valuable tool for the differentiation of positional isomers.
AB  - Cinnamylideneacetophenones have been extensively used as versatile starting
      materials in numerous different transformations. The structural characterization
      of this type of compounds is, therefore, of crucial importance since it can give
      information on the chemistry, reactivity and also the potential biological
      activity of this type of compounds. Thus, 24 derivatives were systematically
      studied by tandem mass spectrometry (MS(2)) with electrospray ionization (ESI),
      in positive ion mode. The protonated molecules, [M + H](+), formed under ESI
      conditions were induced to dissociate and the fragmentation patterns were
      studied. The information collected provided important structural information on
      the type of substituents present and constitute an important database concerning
      this family of compounds. Overall, it was found that the substitution pattern of
      the cinnamylideneacetophenone derivatives changes the ESI-MS(2) fragmentation
      considerably. These results indicate that ESI-MS(2) is a useful technique for
      distinguishing positional isomers of these cinnamylideneacetophenone derivatives.

PMID- 21953976
TI  - Comments on "Application of laser ablation multicollector inductively coupled
      plasma mass spectrometry for the measurement of calcium and lead isotope ratios
      in packaging for discriminatory purposes".

PMID- 21953978
TI  - Highly superporous cholesterol-modified poly(2-hydroxyethyl methacrylate)
      scaffolds for spinal cord injury repair.
AB  - Modifications of poly(2-hydroxyethyl methacrylate) (PHEMA) with cholesterol and
      the introduction of large pores have been developed to create highly superporous
      hydrogels that promote cell-surface interactions and that can serve as a
      permissive scaffold for spinal cord injury (SCI) treatment. Highly superporous
      cholesterol-modified PHEMA scaffolds have been prepared by the bulk radical
      copolymerization of 2-hydroxyethyl methacrylate (HEMA), cholesterol methacrylate
      (CHLMA), and ethylene dimethacrylate (EDMA) cross-linking agent in the presence
      of ammonium oxalate crystals to establish interconnected pores in the scaffold.
      Moreover, 2-[(methoxycarbonyl)methoxy]ethyl methacrylate (MCMEMA) was
      incorporated in the polymerization recipe and hydrolyzed, thus introducing
      carboxyl groups in the hydrogel to control its swelling and softness. The
      hydrogels supported the in vitro adhesion and proliferation of rat mesenchymal
      stem cells. In an in vivo study of acute rat SCI, hydrogels were implanted to
      bridge a hemisection cavity. Histological evaluation was done 4 weeks after
      implantation and revealed the good incorporation of the implanted hydrogels into
      the surrounding tissue, the progressive infiltration of connective tissue and the
      ingrowth of neurofilaments, Schwann cells, and blood vessels into the hydrogel
      pores. The results show that highly superporous cholesterol-modified PHEMA
      hydrogels have bioadhesive properties and are able to bridge a spinal cord
      lesion.

PMID- 21953979
TI  - Effect of dextran layer on protein uptake to dextran-grafted adsorbents for ion
      exchange and mixed-mode chromatography.
AB  - In the current research, a series of dextran-grafted adsorbents were prepared
      using sulfopropyl and 4-(1H-imidazol-1-yl) aniline as chromatographic ligands for
      ion-exchange (IEC) and mixed-mode chromatography (MMC) to respectively
      investigate the influence of dextran layer on adsorption of gamma-globulin.
      Experimental evidences of static adsorption on dextran-grafted IEC adsorbents
      showed that adsorption capacity of gamma-globulin increased with dextran content.
      It could be attributed to the multilayer adsorption of charged protein in dextran
      layer and thus further induced a significant electrical potential gradient at the
      boundary of adsorbed area and its proximity, improving mass transfer in
      combination with concentration gradient. In contrast to IEC adsorbents,
      adsorption capacity and effective diffusivity of dextran-grafted MMC adsorbents
      did not change obviously with dextran grafting. It was considered that
      hydrophobic ligands immobilized onto dextran-grafted MMC adsorbents were stuck
      together at pH 8.0, resulting in the collapse of dextran layer. In concert with
      measured effective porosity for gamma-globulin at pH 4.0, it was confirmed that
      dextran layer in MMC adsorbent was more complicated and influenced significantly
      by buffer pH. It was also manifested by protein adsorption at different pHs.
      Thus, it revealed the complexity in intraparticle mass transfer of the protein in
      dextran-grafted MMC adsorbent.

PMID- 21953980
TI  - Audiovisual synchrony enhances BOLD responses in a brain network including
      multisensory STS while also enhancing target-detection performance for both
      modalities.
AB  - The brain seeks to combine related inputs from different senses (e.g., hearing
      and vision), via multisensory integration. Temporal information can indicate
      whether stimuli in different senses are related or not. A recent human fMRI study
      (Noesselt et al. [2007]: J Neurosci 27:11431-11441) used auditory and visual
      trains of beeps and flashes with erratic timing, manipulating whether auditory
      and visual trains were synchronous or unrelated in temporal pattern. A region of
      superior temporal sulcus (STS) showed higher BOLD signal for the synchronous
      condition. But this could not be related to performance, and it remained unclear
      if the erratic, unpredictable nature of the stimulus trains was important. Here
      we compared synchronous audiovisual trains to asynchronous trains, while using a
      behavioral task requiring detection of higher-intensity target events in either
      modality. We further varied whether the stimulus trains had predictable temporal
      pattern or not. Synchrony (versus lag) between auditory and visual trains
      enhanced behavioral sensitivity (d') to intensity targets in either modality,
      regardless of predictable versus unpredictable patterning. The analogous contrast
      in fMRI revealed BOLD increases in several brain areas, including the left STS
      region reported by Noesselt et al. [2007: J Neurosci 27:11431-11441]. The
      synchrony effect on BOLD here correlated with the subject-by-subject impact on
      performance. Predictability of temporal pattern did not affect target detection
      performance or STS activity, but did lead to an interaction with audiovisual
      synchrony for BOLD in inferior parietal cortex.

PMID- 21953981
TI  - Aligned electrospun scaffolds and elastogenic factors for vascular cell-mediated
      elastic matrix assembly.
AB  - Strategies to enhance the production of organized elastic matrix by smooth muscle
      cells (SMCs) are critical in engineering functional vascular conduits. Therefore,
      the goal of this study was to determine the effect of different surfaces, i.e.
      random and aligned electrospun poly(epsilon-caprolactone) meshes and two
      dimensional (2D) controls, and exogenous elastogenic factors on the cultured rat
      aortic SMC phenotype and production of extracellular matrix. This study
      demonstrated that aligned electrospun fibres guide cell alignment, induce a more
      elongated cell morphology and promote a more synthetic phenotype. Importantly,
      these cells produced greater amounts of elastin-rich matrix per cell on the
      electrospun scaffolds. In addition, exogenous elastogenic factors severely
      limited rat aortic smooth muscle cells (RASMCs) proliferation and promoted a more
      synthetic SMC phenotype on electrospun meshes, but they had less effect on 2D
      controls. Finally, the elastogenic factors induced the SMCs to generate more
      matrix collagen and elastin on a per cell basis. Together, these results
      demonstrate the elastogenic benefits of electrospun meshes.

PMID- 21953982
TI  - Comparison between prenatal ultrasound and postmortem findings in fetuses and
      infants with developmental anomalies.
AB  - OBJECTIVE: To determine if postmortem examinations of fetuses and infants change
      the diagnosis obtained at prenatal ultrasound and affect counseling of future
      pregnancies, and if there has been a change over recent years in the accuracy of
      prenatal ultrasound diagnosis. METHODS: This was a retrospective review of 455
      autopsies of fetuses and infants with developmental anomalies performed at
      Trondheim University Hospital between 1995 and 2004 and with a prenatal
      ultrasound examination performed at a tertiary referral center. The routine
      ultrasound examinations were performed by specially trained midwives and
      obstetricians, referral scans by fetal medicine experts and autopsies by
      consultant pathologists with experience in perinatal pathology. The results of
      this study were also compared with those of a previous similar study performed
      between 1985 and 1995, with fetuses and infants coming from the same population
      and diagnosed at the same center. RESULTS: Of all cases analyzed during the study
      period, there was complete agreement between prenatal ultrasound and postmortem
      findings in 84% (384/455), i.e. prenatal ultrasound diagnoses were supplemented
      by postmortem examinations in 16% (71/455). Autopsy findings in four of these
      cases influenced further counseling. There was agreement regarding the main
      diagnosis in 98% (445/455) of cases. In the previous 10-year period, there was
      complete agreement in 75% and the main diagnosis was correct in 90% of cases.
      These differences between the two time periods were statistically significant (P
      = 0.0004 and P < 0.0001, respectively). The most frequent defects involved the
      central nervous system, heart and urinary tract. For these defects, detection
      rates for the main diagnoses were significantly better in 1995-2004 compared with
      in the previous 10-year period (P = 0.0125, P = 0.0111 and P = 0.0241,
      respectively). CONCLUSION: The accuracy of prenatal sonographic detection of
      developmental anomalies has increased in recent years. However, postmortem
      examination is still necessary to verify or improve the prenatal diagnosis and
      may influence future counseling.

PMID- 21953983
TI  - In situ RBL receptor visualization and its mediated anticancer activity for
      solasodine rhamnosides.

PMID- 21953984
TI  - Macrocyclic multicenter complexes of nickel and copper of increasing complexity.
AB  - Multicenter (bi-, tri-, and tetranuclear) tetraazamacrocyclic complexes were self
      assembled from Ni and Cu tetraazamacrocyclic mononuclear units and alpha,omega
      diamines as building blocks. The structures of all compounds studied were proved
      by spectroscopic methods (ESI MS and NMR spectroscopy). Electrochemical
      experiments revealed reversible one-electron electrode processes at each of the
      Ni(2+)  and Cu(2+)  centers with formation of metal cations in oxidation state
      +3. Long linkers allow bi- and trinuclear complexes with noninteracting metal
      centers to be obtained. In the case of the short linkers (e.g. ethylenediamine)
      higher, trinuclear species are formed as major product. The structures of the bis
      and tris-macrocyclic systems were confirmed by single-crystal X-ray diffraction.
      The tris-macrocyclic systems form cations in the shape of triangles partially
      filled with counterions and solvent molecules. The cations form positively
      charged layers, which interact in the crystal lattice with the neighboring
      negatively charged layers of anions. In solution, the trinuclear complexes
      exhibit strong host-guest interactions with 9,10-dimethyltriptycene due to
      complementarity of shape and size of this guest molecule. The association
      constants were determined by NMR spectroscopy and voltammetry, and very good
      agreement was obtained. The structural flexibility of the tetranuclear complex
      with long linkers allows for attractive interactions between the metal-complexing
      macrocycles that result in folding of the molecule. On the contrary, no folding
      is possible in the case of short linkers consisting of two CH(2)  groups.

PMID- 21953985
TI  - Protein stability and in vivo concentration of missense mutations in
      phenylalanine hydroxylase.
AB  - A previous computational analysis of missense mutations linked to monogenic
      disease found a high proportion of missense mutations affect protein stability,
      rather than other aspects of protein structure and function. The purpose of this
      study is to relate the presence of such stability damaging missense mutations to
      the levels of a particular protein present under "in vivo" like conditions, and
      to test the reliability of the computational methods. Experimental data on a set
      of missense mutations of the enzyme phenylalanine hydroxylase (PAH) associated
      with the monogenic disease phenylketonuria (PKU) have been compared with the
      expected in vivo impact on protein function, obtained using SNPs3D, an in silico
      analysis package. A high proportion of the PAH mutations are predicted to be
      destabilizing. The overall agreement between predicted stability impact and
      experimental evidence for lower protein levels is in accordance with the
      estimated error rates of the methods. For these mutations, destabilization of
      protein three-dimensional structure is the major molecular mechanism leading to
      PKU, and results in a substantial reduction of in vivo PAH protein concentration.
      Although of limited scale, the results support the view that destabilization is
      the most common mechanism by which missense mutations cause monogenic disease. In
      turn, this conclusion suggests the general therapeutic strategy of developing
      drugs targeted at restoring wild type stability.

PMID- 21953987
TI  - Rebuttal: Location of femoral artery access and correlation with vascular
      complications.

PMID- 21953986
TI  - The effect of storage medium on the elution of monomers from composite materials.
AB  - The aim of this study was to evaluate the effect of four different storage media
      on the elution of monomers from two composite materials. Samples (n = 10,
      diameter: 4.5 mm, thickness: 2 mm) of two different composite materials (Ceram
      XTM & FiltekTM Supreme XT) were stored after polymerization in four different
      media (NaCl, saliva, ethanol 75% & acetone) for 24 h, 7 days, and 28 days. From
      the storage medium of each tested time period, samples were prepared and analyzed
      by LC-MS/MS, for the elution of BisGMA, TEGDMA, HEMA, Bisphenol A, and two types
      of UDMA. No monomers were detected in the samples of Ceram XTM, independently of
      the storage medium used. In the samples of FiltekTM Supreme XT, no Bisphenol A,
      HEMA, and UDMA 1 were found. BisGMA was detected only in the ethanol and acetone
      samples. The amount of BisGMA eluted in acetone was significant higher compared
      with ethanol 75% (p < 0.0001). TEGDMA was the only monomer that could be detected
      in all tested storage media. Storage in acetone resulted in higher release of
      TEGDMA when compared with other media. The amount of TEGDMA released in saliva
      was similar to the one released in ethanol 75%. It can be concluded that acetone
      is not a suitable medium for elution experiments and although ethanol 75% can
      simulate saliva concerning the elution of TEGDMA, it does not represent a
      laboratory substitute of saliva with respect to the elution of monomers like
      BisGMA.

PMID- 21953988
TI  - Development of isoxazoline-containing peptidomimetics as dual alphavbeta3 and
      alpha5beta1 integrin ligands.
AB  - Isoxazoline-containing peptidomimetics, designed to be effective alpha(v)beta(3)
      and alpha(5)beta(1) integrin ligands, were synthesized through an original
      procedure involving N,O-bis(trimethylsilyl)hydroxyamine conjugate addition to
      alkylidene acetoacetates, followed by intramolecular hemiketalization. To mimic
      the RGD recognition sequence, basic and acidic terminal appendages were
      introduced, and the final products were tested in cell adhesion inhibition
      assays. All the synthesized compounds proved to be excellent ligands for both
      integrin receptors, and a strong influence on intracellular signaling and
      phosphorylation pathways was demonstrated by evaluation of fibronectin-induced
      phosphorylation of ERK. The molecular basis of the observed inhibitory activity
      was suggested on the results of docking experiments.

PMID- 21953989
TI  - Au-Pd core-shell nanoparticles catalyze Suzuki-Miyaura reactions in water through
      Pd leaching.

PMID- 21953990
TI  - Pain in Parkinson's disease.
AB  - Pain and other nonmotor symptoms in PD are increasingly recognized as a major
      cause of reduced health-related quality of life. Pain in PD may be categorized
      into a number of different subtypes, including musculoskeletal, dystonic,
      radicular neuropathic, and central pain. The onset of pain can vary in relation
      to motor symptoms, and may precede the appearance of motor symptoms by several
      years, or occur after the diagnosis of PD has been made. Pain in PD is frequently
      under-recognized and is often inadequately treated. Levodopa-related dystonia may
      respond to manipulation of dopaminergic medication. Dopaminergic therapy may also
      improve musculoskeletal pain related to rigidity and akinesia, as well as
      akathisia in PD. Botulinum toxin injections can be effective for treatment of
      painful focal dystonia. Pain and dysesthesia have been reported to improve with
      DBS, in some cases. Increased understanding of basal ganglia pathways has
      provided further insights into the pathogenesis of pain in PD, but the exact
      mechanism of pain processing and modulation remains unclear.

PMID- 21953991
TI  - Modeling metal bioaccumulation in the invasive mussels Dreissena polymorpha and
      Dreissena rostriformis bugensis in the rivers Rhine and Meuse.
AB  - The metal-specific covalent index and the species-specific size-based filtration
      rate were integrated into a biokinetic model estimating metal bioaccumulation in
      mussels from the dissolved phase and phytoplankton. The model was validated for
      zebra (Dreissena polymorpha) and quagga (Dreissena rostriformis bugensis) mussels
      in the rivers Rhine and Meuse, the Netherlands. The model performed well in
      predicting tissue concentrations in different-sized zebra mussels from various
      sampling sites for (55) Mn, (56) Fe, (59) Co, (60) Ni, (82) Se, (111) Cd, (118)
      Sn, and (208) Pb (r(2) =0.71-0.99). Performance for (52) Cr, (63) Cu, (66) Zn,
      (68) Zn, and (112) Cd was moderate (r(2) <0.20). In quagga mussels, approximately
      73 to 94% of the variability in concentrations of (82) Se, (111) Cd, (112) Cd,
      and (208) Pb was explained by the model (r(2) =0.73-0.94), followed by (52) Cr,
      (55) Mn, (56) Fe, (60) Ni, and (63) Cu (r(2) =0.48-0.61). Additionally, in both
      zebra and quagga mussels, average modeled concentrations were within
      approximately one order of magnitude of the measured values. In particular, in
      zebra mussels, estimations of (60) Ni and (82) Se concentrations were equal to 51
      and 76% of the measurements, respectively. Higher deviations were observed for
      (52) Cr, (59) Co, (55) Mn, (56) Fe, (111) Cd, (63) Cu, and (112) Cd
      (underestimation), and (66) Zn, (68) Zn, (208) Pb, and (118) Sn (overestimation).
      For quagga mussels, modeled concentrations of (66) Zn and (68) Zn differed
      approximately 14% from the measured levels. Differences between predictions and
      measurements were higher for other metals.

PMID- 21953992
TI  - Exposure to inhibitors of the renin-angiotensin system is a major independent
      risk factor for acute renal failure induced by sucrose-containing intravenous
      immunoglobulins: a case-control study.
AB  - PURPOSE: Risk factors for intravenous immunoglobulin-induced renal failure (IVIg
      RF) were suspected from case series studies. This study was aimed at quantifying
      the risk of IVIg-RF associated with exposure to drugs that modify intrarenal
      hemodynamics. METHODS: We conducted a case-control study in the French
      Pharmacovigilance Database (FPVD). Adult IVIg-RF cases registered in the FPVD
      from 1996 to 2009 were reviewed. Controls were patients included in the FPVD for
      another IVIg adverse effect. Controls were matched for sucrose content of the
      preparation, year of adverse event and age. The predictors of IVIg-RF were
      exposure to angiotensin-converting enzyme inhibitors (ACE-I), angiotensin
      receptor antagonists (ARA), diuretics, age, gender and weight, IVIg delivered
      dose and infusion duration, chronic kidney disease, hypertension and diabetes
      mellitus. Acute IVIg-RF was defined as a calculated creatinine clearance less
      than 60 mL/min and, in the event of chronic kidney disease, (i) a more than 50%
      increase of serum creatinine, (ii) an indication of oligo-anuria or (iii) a
      requirement for dialysis. RESULTS: We selected 71 cases and 71 controls. Forty
      nine percent of the cases required transient hemodialysis. In the final
      multivariate model, exposure to ACE-I and/or ARA was the sole independent
      predictor associated with IVIg-RF (OR = 7.9, 95%CI = 1.3-49.2). There was an
      interaction between 'diabetes mellitus' (OR = 7.7, 95%CI = 2.3-25.5) and 'chronic
      kidney disease' (OR = 13.0, 95%CI = 3.1-54.7), both being strong risk factors in
      univariate models (p < 0.001). Chronic hypertension was a risk factor for
      hemodialysis. CONCLUSIONS: Temporary interruption of ACE-I and ARA may be
      considered at the time of IVIg infusion.

PMID- 21953993
TI  - Metastatic proximal epithelioid sarcoma in pleural effusion: cytopathologic
      findings and differential diagnosis.
AB  - We present a rare occurrence of metastatic proximal epithelioid sarcoma (PES) in
      the pleural effusion of a 23-year-old man, developed within one year of diagnosis
      in his gluteal soft tissue. The cytologic and immunoperoxidase findings are
      described. PES, due to its epithelioid morphology, can be confused with more
      common cancers in effusions such as adenocarcinoma and mesothelioma. PES is an
      aggressive neoplasm that differs clinically and pathologically from conventional
      epithelioid sarcoma. Knowledge of its cytomorphology in serous cavity effusions,
      a patient's clinical history and ancillary studies may lead to an accurate
      diagnosis.

PMID- 21953994
TI  - Quantitative T2 mapping of femoral head cartilage in systemic lupus erythematosus
      patients with noncollapsed osteonecrosis of the femoral head associated with
      corticosteroid therapy.
AB  - PURPOSE: To evaluate articular cartilage degeneration with transverse relaxation
      time (T2) mapping in systemic lupus erythematosus (SLE) patients with
      noncollapsed and asymptomatic osteonecrosis of the femoral head associated with
      corticosteroids. MATERIALS AND METHODS: T2 mapping with a 1.5-T magnetic
      resonance imaging system was prospectively performed for 28 normal hips from 14
      healthy volunteers (control group) and 15 hips from 10 SLE patients that met the
      inclusion criteria of noncollapsed and asymptomatic osteonecrosis of the femoral
      head (osteonecrosis group). Exclusion criteria were past experience of pain,
      trauma, infection, or prior hip joint surgery. Distribution of T2 values of the
      femoral head cartilage were compared between the control group and the
      osteonecrosis group with respect to acetabular dysplasia by center-edge angle
      (CEA). RESULTS: T2 values of the femoral head cartilage were significantly higher
      in the osteonecrosis group than in the control group (34.4 msec vs. 30.8 msec, P
      = 0.001). Multiple regression analysis revealed that the osteonecrosis group and
      decreased CEA was significantly associated with high T2 values (T2 value = 34.6 +
      3.6 * [osteonecrosis] - 0.14 * CEA, R(2) = 0.52, P = 0.003). CONCLUSION:
      Degeneration of articular cartilage was associated with osteonecrosis of the
      femoral head in SLE patients and acetabular dysplasia.

PMID- 21953995
TI  - Antioxidant, cytotoxic activities, and structure-activity relationship of gallic
      acid-based indole derivatives.
AB  - A new series of gallic hydrazones containing an indole moiety was synthesized
      through the reaction of gallic hydrazide and different indole carboxaldehydes.
      Their antioxidant activities were determined on DPPH radical scavenging and
      inhibition of lipid peroxidation. The in-vitro cytotoxic activities of the
      compounds were evaluated against HCT-116 (human colon cancer cell line) and MCF-7
      (estrogen-dependent human breast cancer cell line) by the MTT method. An attempt
      to correlate the biological results with their structural characteristics has
      been done. A limited positive structure activity relationship was found between
      cytotoxic and antioxidant activities.

PMID- 21953996
TI  - Near-infrared light emission from a GaN/Si nanoheterostructure array.

PMID- 21953997
TI  - RNA separation by in-capillary denaturing polymer electrophoresis with 1,2,5
      thiadiazole as an additive.
AB  - 1,2,5-Thiadiazole improved RNA separation with in-capillary denaturing polymer
      electrophoresis. 1,2,5-Thiadiazole was synthesized as an extraction solvent
      substituted for a halogenated solvent. While 1,2,5-thiadiazole was an excellent
      extraction solvent and an environmentally friendly solvent, we found that 1,2,5
      thiadiazole was a strong hydrophobic compound for RNA and the RNA separation
      performance by in-capillary denaturing polymer electrophoresis was dramatically
      improved. We suggest "in-capillary denaturing polymer electrophoresis" as an RNA
      separation that realizes the denaturing and separation simultaneously. RNA
      separation by the method required a strong denaturant, acetic acid, to cleave the
      intramolecular hydrogen. The running buffer containing acetic acid was of high
      conductivity and low pH, in which the condition introduced Joule heating and low
      sensitivity. While conventional denaturants, formaldehyde and urea, maintained
      small electric conductivity and neutral pH, these denaturants were too weak to
      achieve the RNA separation by in-capillary denaturing polymer electrophoresis.
      1,2,5-Thiadiazole being a neutral molecule, both conductivity and buffer pH were
      able to be adjusted to a desirable strength for RNA separation. In this paper, we
      report that RNA separation by in-capillary denaturing polymer electrophoresis in
      neutral pH was achieved and the sensitivity for RNA separation was higher than
      that for RNA separation by in-capillary denaturing polymer electrophoresis with
      acetic acid.

PMID- 21953998
TI  - High sensitivity 19F MRI of a perfluorooctyl bromide emulsion: application to a
      dynamic biodistribution study and oxygen tension mapping in the mouse liver and
      spleen.
AB  - We have recently developed an optimized multi-spin echo (MSE) sequence dedicated
      to perfluorooctyl bromide (PFOB) imaging yielding an excellent sensitivity in
      vitro. The aim of the present study was to apply this sequence to quantitative
      measurements in the mouse liver and spleen after intravenous (i.v.) injection of
      PFOB emulsions. We first performed oxygenation maps 25.5 min after a single
      infusion of emulsion and, contrary to previous studies, shortly after injection.
      The signal-to-noise ratio (SNR) in the liver and spleen was as high as 45 and
      120, respectively, for 3-min images with 11.7-MUL pixels. Values of oxygen
      tension tended to be slightly higher in the spleen than in the liver. Dynamic
      biodistribution experiments were then performed immediately after intravenous
      (i.v.) injection of PFOB emulsions grafted with different quantities of
      polyethylene glycol (PEG) for stealth. Images were acquired every 7 min for 84
      min and the SNR measured in the liver and spleen was at least four from the first
      time point. Uptake rates could be assessed for each PEG amount and, in spite of
      high standard deviations (SDs) owing to interanimal variability, our data
      confirmed that increasing quantities of PEG allow more gradual uptake of the
      emulsion particles by the liver and spleen. In conclusion, our method seems to be
      a powerful tool to non-invasively perform accurate in vivo quantitative
      measurements in the liver and spleen using (19)F MRI.

PMID- 21953999
TI  - The suitability of human adipose-derived stem cells for the engineering of
      ligament tissue.
AB  - Rupture of the anterior cruciate ligament (ACL) is the one of the most common
      sports-related injuries. With its poor healing capacity, surgical reconstruction
      using either autografts or allografts is currently required to restore function.
      However, serious complications are associated with graft reconstructions and the
      number of such reconstructions has steadily risen over the years, necessitating
      the search for an alternative approach to ACL repair. Such an approach may likely
      be tissue engineering. Recent engineering approaches using ligament-derived
      fibroblasts have been promising, but the slow growth rate of such fibroblasts in
      vitro may limit their practical application. More promising results are being
      achieved using bone marrow mesenchymal stem cells (MSCs). The adipose-derived
      stem cell (ASC) is often proposed as an alternative choice to the MSC and, as
      such, may be a suitable stem cell for ligament engineering. However, the use of
      ASCs in ligament engineering still remains relatively unexplored. Therefore, in
      this study, the potential use of human ASCs in ligament tissue engineering was
      initially explored by examining their ability to express several ligament markers
      under growth factor treatment. ASC populations treated for up to 4 weeks with
      TGFbeta1 or IGF1 did not show any significant and consistent upregulation in the
      expression of collagen types 1 and 3, tenascin C and scleraxis. While treatment
      with EGF or bFGF resulted in increased tenascin C expression, increased
      expression of collagens 1 and 3 were never observed. Therefore, simple in vitro
      treatment of human ASC populations with growth factors may not stimulate their
      ligament differentiative potential.

PMID- 21954002
TI  - Bridging eta2 -BO in B2(BO)3(-) and B3(BO)3(-) clusters: boronyl analogs of
      boranes.
AB  - Anion photoelectron spectroscopy and theoretical calculations are combined to
      probe the structures and chemical bonding of two boron-rich oxide clusters,
      B(5)O(3)(-) and B(6)O(3)(-), which are shown to be appropriately formulated as
      B(2)(BO)(3)(-) and B(3)(BO)(3)(-), respectively. The anion clusters are found to
      each possess a bridging eta(2)-BO group, as well as two terminal BO groups and
      are analogs of B(2)H(3)(-) and B(3)H(3)(-). This finding advances the boronyl
      chemistry and helps establish the isolobal analogy between boron-rich oxide
      clusters and boranes.

PMID- 21954000
TI  - What's the story? The tale of reading fluency told at speed.
AB  - Fluent readers process written text rapidly and accurately, and comprehend what
      they read. Historically, reading fluency has been modeled as the product of
      discrete skills such as single word decoding. More recent conceptualizations
      emphasize that fluent reading is the product of competency in, and the
      coordination of, multiple cognitive sub-skills (a multi-componential view). In
      this study, we examined how the pattern of activation in core reading regions
      changes as the ability to read fluently is manipulated through reading speed. We
      evaluated 13 right-handed adults with a novel fMRI task assessing fluent sentence
      reading and lower-order letter reading at each participant's normal fluent
      reading speed, as well as constrained (slowed) and accelerated reading speeds.
      Comparing fluent reading conditions with rest revealed regions including
      bilateral occipito-fusiform, left middle temporal, and inferior frontal gyral
      clusters across reading speeds. The selectivity of these regions' responses to
      fluent sentence reading was shown by comparison with the letter reading task.
      Region of interest analyses showed that at constrained and accelerated speeds
      these regions responded significantly more to fluent sentence reading.
      Critically, as reading speed increased, activation increased in a single reading
      related region: occipital/fusiform cortex (left > right). These results
      demonstrate that while brain regions engaged in reading respond selectively
      during fluent reading, these regions respond differently as the ability to read
      fluently is manipulated. Implications for our understanding of reading fluency,
      reading development, and reading disorders are discussed.

PMID- 21954003
TI  - Ion-beam-induced desorption as a method for probing the stability of the molecule
      substrate interface in self-assembled monolayers.

PMID- 21954004
TI  - A method for conformational sampling of loops in proteins based on adiabatic
      decoupling and temperature or force scaling.
AB  - A method for conformational Boltzmann sampling of loops in proteins in aqueous
      solution is presented that is based on adiabatic decoupling molecular dynamics
      (MD) simulation with temperature or force scaling. To illustrate the enhanced
      sampling, the loop from residues 33 to 43 in the bovine protein ribonuclease A is
      adiabatically decoupled from the rest of the protein and the solvent with a mass
      scaling factor s(m) =1000 and the sampling is enhanced with a scaling of the
      temperature using s(T) =2 or of the force using s(V) =0.667. Over 5 ns of
      simulation the secondary structure of the protein remains unaltered while a
      combined dihedral-angle conformational cluster analysis shows an increase of
      conformations outside the first most populated cluster of loop conformations for
      adiabatic decoupling MD with temperature scaling using s(T) =2 or force scaling
      using s(V) =0.667 compared to the standard MD simulation. The atom-positional
      root-mean-square fluctuations of the C(alpha) atoms of the loop show an increase
      in the movement of the loop as well, indicating that adiabatic decoupling MD with
      upscaling of the temperature or downscaling of the force is a promising method
      for conformational Boltzmann sampling.

PMID- 21954005
TI  - Influence of Mg(2+) on the guanine-cytosine tautomeric equilibrium: simulations
      of the induced intermolecular proton transfer.
AB  - Metallic ions are essential for stabilizing the nucleic acid structure, and are
      also involved in the majority of RNA and DNA biological functions. However, at
      large concentrations metals may play an opposite role by promoting alterations in
      the genetic code (mutagenicity). To contribute to the understanding of this
      effect, theoretical tools are used to investigate the influence of the magnesium
      dication on the guanine-cytosine (GC) base pair structure and stability. To this
      end, a fully hydrated Mg(2+) cation is inserted in two models: an isolated GC
      base pair, and a more realistic DNA model corresponding to a hydrated double
      stranded trimer. Calculations performed with a hybrid ONIOM approach reveal that
      the Mg(2+) cation coordination to the GC base pair alters drastically the natural
      tautomeric equilibria in DNA by promoting single proton transfer. Nevertheless,
      the generated rare tautomer will have a limited impact on the total spontaneous
      mutation due to the low back-reaction barrier allowing a quick return to the
      canonical form. Additionally, it is demonstrated that the major effects of
      biological environment arise from the hydration and stacking influence, whereas
      the impact of phosphate groups is minor.

PMID- 21954006
TI  - Structure and photoelectron spectral properties of I(-).nCO2 clusters: an ab
      initio study.
AB  - Structures and photoelectron spectral properties of I(-).nCO(2) (n=1-7) clusters
      are presented at the level of second-order Moller-Plesset perturbation theory
      with relativistic corrections. Triple split-valence 6-311++G(d,p) basis set
      functions are employed herein. It is observed that the CO(2) molecules approach
      the I(-) anion from one side in all the clusters and that I(-).nCO(2) clusters
      prefer the surface structure. The calculated vertical detachment energy of these
      clusters is in excellent agreement with the reported experimentally measured
      values (within 4%). Efforts are also made to extract vertical detachment energy
      of large size of clusters, including the bulk. The extracted vertical detachment
      energy values for larger clusters (n=8-13) by employing the microscopic theory
      based expression are also close (within 4%) to that of the experimentally
      measured values.

PMID- 21954009
TI  - Effect of vascular endothelial growth factor gene transfer on infarct size, left
      ventricular function and myocardial perfusion in sheep after 2 months of coronary
      artery occlusion.
AB  - BACKGROUND: In large mammalian models of acute myocardial infarction (AMI),
      plasmid-mediated vascular endothelial growth factor (pVEGF) gene transfer has
      been shown to induce angio-arteriogenesis, proliferation of myocyte precursors
      and adult cardiomyocyte mitosis, reducing infarct size at 15 days after coronary
      artery occlusion. However, it is unknown whether these effects persist at longer
      follow-up times, nor how they affect cardiac performance. We thus assessed
      infarct size, left ventricular (LV) function and perfusion in 2-month-old ovine
      AMI. METHODS: Adult sheep with coronary artery occlusion were randomized to
      blindly receive ten intramyocardial injections of 3.8 mg of pVEGF or empty
      plasmid distributed at the infarct border. Three and 60 days later, LV perfusion
      (single-photon emission computed tomography) and function (stress
      echocardiography) were assessed. Finally, hemodynamics (LV catheterization), scar
      size and peri-infarct histology were studied. RESULTS: Infarct size was 30%
      smaller in pVEGF-treated sheep (23.6 +/- 1.9% versus 32.7 +/- 2.7% of the LV; p <
      0.02). Percentage fractional shortening and wall thickening at the infarct border
      improved after pVEGF, as did myocardial perfusion and LV wall motion under
      pharmacological stress. Global LV function did not differ between groups,
      although the force-frequency response was preserved in pVEGF group and lost in
      placebo animals. These effects were associated with angio-arteriogenesis and
      proliferation of cardiomyocyte precursors. CONCLUSIONS: In sheep with AMI, pVEGF
      gene transfer affords long-term infarct size reduction, yielding regional LV
      function and perfusion improvement and reducing remodeling progression. These
      results suggest the potential usefulness of this approach in the clinical
      setting.

PMID- 21954011
TI  - Macrophage response to high number of titanium particles is cytotoxic and COX-2
      mediated and it is not affected by the particle's endotoxin content or the
      cleaning treatment.
AB  - Periprosthetic osteolysis is a progressive deterioration of bone around
      prostheses resulting primarily from the presence of wear debris. Particulate
      material, number, and their interactions with environmental factors play
      important roles in macrophage activation around implants. We have previously
      shown that macrophages cultured in the presence of high numbers of cleaned
      titanium (Ti) particles released significant amounts of PGE2 that is potentially
      detrimental for bone. Cleaning of particles has become routine in most studies of
      macrophage/particle interactions as contaminating endotoxin elicits a macrophage
      cytokine response and since numerous studies have suggested that endotoxins may
      be present on implant materials. However, the strenuous cleaning procedure itself
      represents a possible source of other contaminants (such as material by-products)
      that may be relevant to the prostanoid response of macrophages. To analyze this
      hypothesis, the macrophage response to high numbers of cleaned Ti particles was
      compared to that of unclean particles and to particles that were subjected to a
      short version of the cleaning procedure. It was found that neither the high
      amount of endotoxin on the unclean particles nor the duration of the cleaning
      procedure had an effect on the release of PGE2 and the decrease in cell viability
      in response to high number of Ti particles. Evidence of a possible relationship
      between these two variables is presented.

PMID- 21954010
TI  - Optimized transgenesis in Xenopus laevis/gilli isogenetic clones for
      immunological studies.
AB  - Xenopus laevis provides a unique animal model, alternative to mouse, to study
      immunology. Even though, several methodologies have been developed for the
      generation of transgenic Xenopus, to date none have been adapted for the X.
      laevis/gilli (LG) isogenetic clones that are essential for immunological studies.
      Since LG clones are generated via gynogenesis, transgenic methods using transgene
      integration into the sperm nuclei are not suited. Therefore, we have tested three
      alternative methods for LG transgenesis: the phiC31 integrase, the Sleeping
      Beauty transposase, and the I-SceI meganuclease. All three techniques produced
      transgenic LG clones; however, the I-SceI meganuclease was most effective. It
      resulted in high transgenesis efficiency (35-50%), bright nonmosaic GFP
      expression as well as stable germline transmission with 100% of the progeny
      carrying the transgene. Production of transgenic LG clones will allow us to
      modulate immune gene expression and further strengthen X. laevis as a biomedical
      model.

PMID- 21954012
TI  - Intermolecular and intracomplex photoinduced electron transfer from planar and
      nonplanar metalloporphyrins to p-quinones.
AB  - The rate constants of intermolecular photoinduced electron transfer from triplet
      excited states of metalloporphyrins to a series of p-benzoquinone derivatives in
      benzonitrile were determined to examine the effects of the driving force, the
      metal, and the conformational distortion of the porphyrin ring on the
      reorganization energies (lambda) of electron transfer by laser flash photolysis.
      The lambda values were evaluated from the determined rate constants on the basis
      of the Marcus theory of electron transfer. The lambda values of planar
      metalloporphyrins, [Al(TPP)(PhCOO)] and [Zn(TPP)] (TPP(2-)=tetraphenylporphyrin
      dianion), are approximately the same, but they are 0.27 eV smaller than those of
      the corresponding nonplanar (saddle-distorted) metalloporphyrins [Al(DPP)(PhCOO)]
      and [Zn(DPP)] (DPP(2-)=dodecaphenylporphyrin dianion) when they are compared for
      the same driving force of photoinduced electron transfer. The axial ligand PhCOO(
      ) of [Al(TPP)](+) and [Al(DPP)](+) was replaced by anthraquinone-2-carboxylate
      (AqCOO(-)) to afford the electron donor-acceptor complexes [Al(TPP)(AqCOO)] and
      [Al(DPP)(AqCOO)], respectively. The X-ray crystal structure of [Al(TPP)(AqCOO)]
      revealed strong coordination of AqCOO(-) to the Al(3+) ion of [Al(TPP)](+) and
      the existence of pi-pi interactions between AqCOO(-) and the porphyrin ring. In
      the case of the saddle-distorted [Al(DPP)(AqCOO)], however, the AqCOO(-) moiety
      is nearly perpendicular to the porphyrin ring. The photodynamics of intracomplex
      photoinduced electron transfer from the singlet excited state of [Al(TPP)](+) and
      [Al(DPP)](+) to the AqCOO(-) moiety were also examined in comparison with the
      intermolecular photoinduced electron-transfer reactions, and the determined rate
      constants were evaluated in light of the Marcus theory of electron transfer to
      reveal that the electron transfer is adiabatic in each case.

PMID- 21954013
TI  - Herxheimer spirals in a liquid-based Pap test showing radiation changes.

PMID- 21954014
TI  - Unprecedented stability of a photochromic bisthienylethene based on
      benzobisthiadiazole as an ethene bridge.

PMID- 21954015
TI  - Synthesis and antioxidant evaluation of some new 3-substituted coumarins.
AB  - 3-Acetylcoumarin (1) was utilized as a key intermediate for the synthesis of 2
      aminothiazole derivative 3 via bromination of 1 to afford acetylbromide 2
      followed by treatment with thiourea or via Biginelli reaction of 1. Treatment of
      3 with 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde, 2-methyl-4H
      benzo[d][1,3]oxazin-4-one, furo[3,4-b]pyrazine-5,7-dione or 2-methyl-5,6,7,8
      tetrahydro-4H-benzothieno[2,3-d][1,3]oxazin-4-one afforded diazine derivatives 4
      7. Also, pyridopyrimidine 8 was obtained via a one pot reaction of 6
      aminothiouracil, p-chlorobenzaldehyde and 3-acetylcoumarin. Moreover, refluxing
      of 6-aminothiouracil with one equivalent amount of 2 afforded the
      thiazolopyrimidine 9, while the pyrrolothiazolopyrimidine 10 was revealed when
      two equivalent amounts of 2 was used. Furthermore, treatment of enamine 11 with 2
      aminobenzothiazole or 6-aminothiouracil afforded the pyrimidine derivatives 12
      and 13, respectively. Transamination of enamine 11 with m-anisidine followed by
      cyclization of the resulting enaminone 14 gave the desired quinoline 15. Also,
      treatment of 11 with thiophenol in dioxane gave the mercapto derivative 16.
      Moreover, coupling of 11 with 4,6-dimethyl-1H-pyrazolo[3,4-b]pyridin-3-yl
      diazonium chloride, followed by complete cyclization of the resulting product
      afforded the pyridopyrazolothiazine 19 via the intermediate 18. Furthermore, the
      pyrazolopyrimidine 20 was revealed via a one pot condensation of 11, 3-methyl-1
      phenyl-1H-pyrazol-5(4H)-one and ammonium acetate. The thiadiazine derivatives 21
      23 were obtained via treatment of 2 with the corresponding o-aminothiols.
      Desulphonation of 23 afforded the pyrazolotriazine 24. Finally, reaction of 2
      with 2-hydroxybenzaldehyde gave benzofuran derivative 25. Representative
      compounds of the synthesized products were evaluated as antioxidant agents.

PMID- 21954016
TI  - Rational syntheses and structural characterization of sulfur-rich phosphorus
      polysulfides: alpha-P2S7 and beta-P2S7.

PMID- 21954017
TI  - Novel rhein analogues as potential anticancer agents.
AB  - Two series of rhein analogues were synthesized with modification at the 3
      position. Their cytotoxicities were evaluated using an MTT assay. Among all the
      compounds synthesized, one compound showed the best potency, with an IC(50) value
      of 2.7 MUM against the HeLa cell line and 0.6 MUM against the MOLT4 cell line.

PMID- 21954019
TI  - Model-based, semiquantitative and time intensity curve shape analysis of dynamic
      contrast-enhanced MRI: a comparison in patients undergoing antiangiogenic
      treatment for recurrent glioma.
AB  - PURPOSE: To compare time intensity curve (TIC)-shape analysis of dynamic contrast
      enhanced magnetic resonance imaging (DCE-MRI) data with model-based analysis and
      semiquantitative analysis in patients with high-grade glioma treated with the
      antiangiogenic drug bevacizumab. MATERIALS AND METHODS: Fifteen patients had a
      pretreatment and at least one posttreatment DCE-MRI. We applied a pixel-by-pixel
      TIC shape analysis, where TICs are classified into five different types according
      to their shape, and calculated the occurrence of each TIC type in the region of
      interest (ROI). The results were compared to the pharmacokinetic model (PKM)
      parameters K(trans) , K(ep) , V(e) , and V(i) , and with the semiquantitative
      parameters maximum enhancement (ME) and initial slope of increase (ISI). RESULTS:
      The relative amount of type 2 and 4 TIC shape significantly correlated with the
      parameter K(ep) but not with K(trans) or V(e) . The PKM parameter V(e) and the
      semiquantitative parameters ME and ISI showed significant changes after
      treatment. None of the TIC shapes individually showed significant changes.
      CONCLUSION: The semiquantitative parameters ME and ISI are more sensitive to the
      effect of the bevacizumab than K(trans) and V(e) . The pixel-by-pixel TIC shape
      analysis parameters are not sensitive to the effect of bevacizumab, although they
      can be seen as surrogates for the PKM parameter K(ep) .

PMID- 21954020
TI  - Evaluation of the representativeness of a Dutch non-malformed control group for
      the general pregnant population: are these controls useful for EUROCAT?
AB  - PURPOSE: A case-control study is the most powerful design to test the risk of
      specific congenital malformations associated with a specific drug. However,
      malformation registries often lack non-malformed controls. For the Dutch EUROCAT,
      we collected a non-malformed control group: the 'Healthy Pregnant'. The aim of
      this study was to evaluate the representativeness of this control group for the
      general pregnant population in the northern part of the Netherlands. METHODS: The
      Healthy Pregnant data set includes data from two midwife practices. The baseline
      characteristics of mother and child including smoking status, drinking status,
      body mass index, maternal age, educational level, exposures to several drugs for
      chronic diseases and pregnancy related symptoms were evaluated. RESULTS: Compared
      with the general population, mothers in Healthy Pregnant group (n = 556) were
      from either low or high education level, were more likely to have a body mass
      index > 25 kg/m2 (26% versus 22%, p = 0.08) or to smoke (19% versus 10%, p <
      0.01) but were less likely to consume alcohol (20% versus 29%, p < 0.01). The use
      of drugs for chronic conditions was lower in Healthy Pregnant group. Furthermore,
      drugs for occasional use were prescribed less frequently, and a significant
      underreporting of children with a low birth weight and a short duration of
      gestation was found. CONCLUSION: The Healthy Pregnant data set was not
      representative of the general pregnant population in the northern part of the
      Netherlands. Specifically, the exposure to (chronic) drugs was underestimated,
      possibly a result of second-line care on the basis of medical indication. Thus,
      continuous investigation of options for improvement of the Healthy Pregnant
      database is required.

PMID- 21954021
TI  - Quantitative analysis of tumor burden in mouse lung via MRI.
AB  - Lung cancer is the leading cause of cancer death in the United States. Despite
      recent advances in screening protocols, the majority of patients still present
      with advanced or disseminated disease. Preclinical rodent models provide a unique
      opportunity to test novel therapeutic drugs for targeting lung cancer.
      Respiratory-gated MRI is a key tool for quantitatively measuring lung-tumor
      burden and monitoring the time-course progression of individual tumors in mouse
      models of primary and metastatic lung cancer. However, quantitative analysis of
      lung-tumor burden in mice by MRI presents significant challenges. Herein, a
      method for measuring tumor burden based upon average lung-image intensity is
      described and validated. The method requires accurate lung segmentation; its
      efficiency and throughput would be greatly aided by the ability to automatically
      segment the lungs. A technique for automated lung segmentation in the presence of
      varying tumor burden levels is presented. The method includes development of a
      new, two-dimensional parametric model of the mouse lungs and a multi-faceted cost
      function to optimally fit the model parameters to each image. Results demonstrate
      a strong correlation (0.93), comparable with that of fully manual expert
      segmentation, between the automated method's tumor-burden metric and the tumor
      burden measured by lung weight.

PMID- 21954022
TI  - Study on molecular mechanism for improving neural regeneration after repair of
      sciatic nerve defect in rat by acellular nerve allograft.
AB  - OBJECTIVE: Discuss the molecular mechanism for improving neural regeneration
      after repair of sciatic nerve defect in rat by acellular nerve allograft (ANA).
      METHODS: Randomly divide 36 Wistar rats into six groups as normal control group,
      autografting group, and bridging groups of 2, 4, 8, 12 weeks, six rats for each
      group. Observe the expression of brain-derived neurotrophic factor (BDNF) in L(4)
      spinal cord and anterior tibial muscle at the injury site, calcitonin gene
      related peptide (CGRP) protein as well as mRNA, respectively. 12w after
      operation, histopathological observation was performed. RESULTS: 2w after ANA
      bridging the sciatic nerve defect in rats, it was observed that the expression
      level of BDNF in spinal cord at the injury site and CGRP protein increased,
      reaching the peak level at 4w, lasting till 8w, then decreased but still
      significantly higher than that in normal control group at 12w, and was not
      significantly different compared with that in autografting group. However, the
      expression level of BDNF in anterior tibial muscle decreased gradually within the
      initial 4w, then increased progressively, reaching normal level at 12w, and was
      not significantly different compared with that in autografting group. The
      expression of BDNF mRNA and CGRPmRNA was essentially the same. 12w after
      operation, there was nerve regeneration in bridging group of 12w and autografting
      group. CONCLUSIONS: ANA possessed fine histocompatibility, and might substitute
      autograft to repair long-segment defect of sciatic nerve in rats. This action
      might be related to upregulation of protein and mRNA expression for BDNF and CGRP
      in spinal cord.

PMID- 21954024
TI  - Highly packed and aligned fluoride substituted hydroxyapatite via a surfactant
      free process.
AB  - Biomolecules and surfactants are believed to be the key factors for
      reconstruction of tooth enamel and preparation of fluoride hydroxyapatite coating
      with enamel-like structure on dental implants. We have developed an alternative
      surfactant-free biomimetic method to stimulate growth of fluoride substituted
      hydroxyapatite coatings with highly packed and aligned structure on metallic
      substrates. Oxidized titanium plates were chosen as the substrates. The
      biomimetic fluoride hydroxyapatite was prepared by immersing the pretreated Ti
      plates into the phosphate-buffered solution with Ca(2+), H(2)PO(4)(-), HPO(4)(2
      ), and F(-). The pH value was controlled at 7.4 at the beginning. Every titanium
      plate (10 mm * 10 mm * 1 mm) was soaked into 20 mL of ion doped phosphate
      buffered solution in sealed plastic bottles, kept at 37 degrees C or 60 degrees C
      without stirring for time periods of 1 day to 2 weeks. After immersion, the
      samples were removed from the solution, rinsed with deionized water and allowed
      to dry in air. The fluoride substituted hydroxyapatite layer, composed of needle
      like crystallites with the diameter of 10-20 nm, was well-organized and tightly
      packed. XRD results showed a sharper and stronger (002) peak, which could be used
      to explain that there was a preferable orientation along the c axis. The coating
      could be reconstructed on the former layer if the mineralization process was
      repeated, and the structure of the coating could be preserved. The method could
      be used to construct well organized fluoride substitute hydroxyapatite coating on
      metal implants.

PMID- 21954023
TI  - Multiple cerebral emboli following dislocation and retraction of a partially
      deployed CoreValve prosthesis during transcatheter aortic valve implantation.
AB  - Transcatheter aortic valve implantation for patients with severe aortic stenosis
      at a high-operative risk has been demonstrated to improve mortality compared to
      standard medical therapy. Registry data and the PARTNER trial have shown a
      significant risk of stroke (3-5%) following the procedure. Studies using cerebral
      diffusion-weighted magnetic resonance imaging have suggested the mechanism of
      stroke to be multiple small embolic infarcts, possibly from aortic atheroma
      dislodged during the movement of the valve and its apparatus around the thoracic
      aorta. The incidence of these infarcts is higher than clinically apparent. The
      Medtronic CoreValve (Medtronic, Minneapolis, Minnesota) prosthesis is a self
      expanding nitinol frame with porcine valve, whose deployment is achieved by the
      retraction of the delivery catheter. Potential complications of this method
      include valve mal-positioning and dislocation. The partially deployed valve may
      then be resheathed following retraction back into the descending aorta and
      subsequently redeployed. We present two such cases with evidence of both "silent"
      and clinically evident cerebral infarction.

PMID- 21954025
TI  - Functionalized conducting polymer nanodots for enhanced cell capturing: the
      synergistic effect of capture agents and nanostructures.

PMID- 21954027
TI  - Nonmotor versus motor symptoms: how much do they matter to health status in
      Parkinson's disease?
AB  - Evidence suggests that both motor and nonmotor symptoms contribute to health
      status in Parkinson's disease. Less clear is how much change in health status can
      be expected if these clinical variables change. In addition, anxiety, separate
      from depression, has rarely been examined as a predictor of health status. We
      used hierarchical multiple regression analysis and standardized beta coefficients
      in a prevalent cohort of 462 patients with Parkinson's disease to explore the
      relative impact on health status (measured using the Parkinson's Disease
      Questionnaire) of 5 well-recognized symptom domains in Parkinson's disease: motor
      signs, depression, anxiety, cognition, and other nonmotor symptoms. In the health
      status scores, 19.6% of variance was explained by age, number of comorbidities,
      disease duration, and levodopa equivalent dose. Younger age predicted worse
      health status. A full regression model containing baseline variables and all 5
      symptom domains explained 56% of the variance in health status. The standardized
      beta coefficient for depression was 2.1, 1.6, and 1.3 times that of motor signs,
      anxiety, and other nonmotor symptoms, respectively. Our findings provide a
      ranking order of clinical variables for their relative impact on health status in
      Parkinson's disease and show that depression has more than twice the impact of
      motor signs on health status. Anxiety and other nonmotor symptoms are also
      important separate determinants of poor health status in Parkinson's disease. Our
      results will help to guide the development of individual care and service
      planning for patients with Parkinson's disease.

PMID- 21954028
TI  - A theoretical study of the 3d-M(smif)2 complexes: structure, magnetism, and
      oxidation states.
AB  - We carry out a theoretical investigation of the recently reported M(smif)(2)
      series1,2 and find a number of interesting phenomena. These include complex
      potential energy surfaces with near-degenerate stationary points, low-lying
      states, non-trivial electron configurations, as well as non-innocent ligand
      behavior. The M(smif)(2) exhibit a delicate balance between geometry and
      electronic structure, which has implications not only for their reactivity but
      also for controlling their properties through ligand design. We address
      methodological issues and show how conceptual quantities such as oxidation states
      and electronic configurations can be extracted through a simple analysis of the
      electron and spin densities-without a complicated examination of the underlying
      orbitals.

PMID- 21954029
TI  - Retrospective LC-QTOF-MS analysis searching for pharmaceutical metabolites in
      urban wastewater.
AB  - The presence of pharmaceuticals in the environment is a matter of major concern
      because of their wide consumption and their potential negative effect on the
      water quality and living organisms. After human and/or veterinary consumption,
      pharmaceuticals can be excreted in unchanged form as the parent compound and/or
      as free or conjugated metabolites. These compounds seem not to be completely
      removed during wastewater treatments and might finally arrive to surface and
      ground waters. Consequently, both parent pharmaceuticals and metabolites are
      target analytes to be considered in analytical methodologies. The satisfactory
      sensitivity in full-acquisition mode, high-resolution, exact mass measurements
      and MS/MS capabilities of hybrid quadrupole time-of-flight (QTOF) mass
      spectrometry make of this technique a powerful analytical tool for the
      identification of organic contaminants. In this study, the use of QTOF-MS with
      the aid of specialised processing-data application managers has allowed the
      retrospective analysis of pharmaceuticals metabolites in urban wastewater without
      the need for additional injection of sample extracts. Around 160 metabolites have
      been investigated in wastewater samples previously analysed only for parent
      compounds using LC-QTOF under MS(E)  mode (simultaneous recording of two
      acquisition functions, at low and high collision energy). The retrospective
      analysis was applied to search for pharmaceutical metabolites in parent-positive
      effluent wastewaters from the Spanish Mediterranean region. Five metabolites,
      such as clopidogrel carboxylic acid or N-desmethyl clarithromycin, were
      identified in the samples.

PMID- 21954026
TI  - Physiological noise reduction using volumetric functional magnetic resonance
      inverse imaging.
AB  - Physiological noise arising from a variety of sources can significantly degrade
      the detection of task-related activity in BOLD-contrast fMRI experiments. If
      whole head spatial coverage is desired, effective suppression of oscillatory
      physiological noise from cardiac and respiratory fluctuations is quite difficult
      without external monitoring, since traditional EPI acquisition methods cannot
      sample the signal rapidly enough to satisfy the Nyquist sampling theorem, leading
      to temporal aliasing of noise. Using a combination of high speed magnetic
      resonance inverse imaging (InI) and digital filtering, we demonstrate that it is
      possible to suppress cardiac and respiratory noise without auxiliary monitoring,
      while achieving whole head spatial coverage and reasonable spatial resolution.
      Our systematic study of the effects of different moving average (MA) digital
      filters demonstrates that a MA filter with a 2 s window can effectively reduce
      the variance in the hemodynamic baseline signal, thereby achieving 57%-58%
      improvements in peak z-statistic values compared to unfiltered InI or spatially
      smoothed EPI data (FWHM = 8.6 mm). In conclusion, the high temporal sampling
      rates achievable with InI permit significant reductions in physiological noise
      using standard temporal filtering techniques that result in significant
      improvements in hemodynamic response estimation.

PMID- 21954030
TI  - Republished editorial: Targeting lung attacks.

PMID- 21954031
TI  - Republished editorial: Following Nero: fiddle while Rome burns, or is there a
      better way?

PMID- 21954032
TI  - Predictors of vibration perception threshold in type 2 diabetic patients with
      proliferative retinopathy.
AB  - PURPOSE OF THE STUDY: Distal peripheral neuropathy (DPN) is a troublesome
      complication of diabetes mellitus (DM). The factors associated with the disease
      are still incompletely understood. The purpose of this study was to investigate
      factors associated with vibration perception threshold (VPT) as a marker of DPN
      in a type 2 diabetic population with advanced microvascular disease. METHODS: The
      study included 203 diabetic patients (117 male, 86 female) with proliferative
      diabetic retinopathy. Subjects were investigated by questionnaires, clinical
      examinations, blood and urine sampling, and review of medical records in the
      period from November 2008 through April 2009. Presence of DPN was defined as VPT
      >=25 V. RESULTS: The mean (+/-SD) age was 65.2 (+/-9.9) years and median (IQR)
      diabetes duration was 18 (10-25) years. Forty-six per cent of subjects were found
      to have DPN, defined as a VPT >=25 V by neurothesiometer testing. Prevalence of
      DPN was found to be associated with age (p=0.038), male gender (p=0.046), low
      haemoglobin (p<0.001), high erythrocyte sedimentation rate (p=0.03), uric acid
      values (p=0.034), and peripheral vascular disease (PVD) (p=0.003) in univariate
      analysis. Multivariate logistic regression analysis revealed male gender (OR
      5.52; p<0.001) and low haemoglobin values (B=-0.58; p<0.001) to be independent
      predictors of VPT >=25 V in subjects with proliferative retinopathy, while linear
      regression analysis revealed male gender (p<0.001), haemoglobin (p=0.001), age
      (p=0.04), and PVD (p=0.001) to be significant predictors of VPT. CONCLUSIONS:
      This study reports a novel independent association of DPN with low haemoglobin
      values. In the study population with type 2 DM and proliferative retinopathy, DPN
      was also independently associated with male gender, age, and PVD. Further studies
      are needed to confirm the association with low haemoglobin and identify the
      underlying mechanism.

PMID- 21954033
TI  - Republished original article: Resident-initiated interventions to improve
      inpatient heart-failure management.
AB  - BACKGROUND: Third-year internal medicine residents participating in a quality
      improvement rotation identified gaps between the Joint Commission's ORYX quality
      guidelines and clinical practices for the inpatient management of heart failure
      (HF) at the William S. Middleton Memorial Veterans Hospital. Residents focused on
      the performance metrics associated with tobacco-cessation counselling
      documentation, ejection fraction assessment and angiotensin-converting enzyme
      inhibitor/angiotensin receptor blocker prescriptions. METHODS: After analysing
      data collected by the External Peer Review Program, residents reviewed the
      institution's admissions and discharge processes with the aim of improving
      quality and compliance. In redesigning these processes, residents created an
      admissions template and a discharge face sheet, and compared specific ORYX
      measure compliance rates before and after institution-wide implementation.
      RESULTS: Following implementation of the tobacco-cessation admissions template,
      100% of HF patients who used tobacco received documented cessation counselling,
      compared with 59% prior to intervention (p<0.01, n=32). Following implementation
      of the mandatory discharge face sheet, 97% of HF patients (compared with 92%
      preintervention, p>0.05) received comprehensive discharge instruction; LV
      function assessment went from 98% to 100% (p>0.05); and angiotensin-converting
      enzyme inhibitor/angiotensin receptor blocker prescription for left ventricular
      systolic dysfunction at discharge (or documentation of a contra-indication) went
      from 82% to 100% (p<0.01, n=48). DISCUSSION: By implementing a standardised
      admissions template and a mandatory discharge face sheet, the hospital improved
      its processes of documentation and increased adherence to quality-performance
      measures. By strengthening residents' learning and commitment to quality
      improvement, the hospital created a foundation for future changes in the systems
      that affect patient care.

PMID- 21954034
TI  - Republished review: An update on contraindications for lung function testing.
AB  - Guidelines on contraindications for lung function tests have been based on expert
      opinion from >30&emsp14;years ago. High-risk contraindications to lung function
      testing are associated with cardiovascular complications such as myocardial
      infarct, pulmonary embolism or ascending aortic aneurysm. Slightly less risky but
      still serious contraindications are predominantly centred on recovery from major
      thoracic, abdominal or head surgery. Less serious surgical procedures will
      present a possible risk, but the RR depends upon whether the lung function is
      essential or can wait until the patient's condition improves. In recent decades
      there have been moves towards less invasive surgical techniques, keyhole surgery
      and new technology such as laser surgery which minimise the amount of collateral
      damage to surrounding tissues. In thoracic surgery there is a shift in emphasis
      to quicker postsurgical mobility. Furthermore there has been little analysis of
      the scientific facts behind the current recommendations and contraindications.
      The principle absolute and relative contraindications are in need of revision,
      and recommended times of abstaining from lung function tests needs to be
      reviewed. This review aims to outline the key issues and suggests newer
      recommendations for contraindications for performing lung function using a risk
      matrix, as well as offering alternative approaches to testing patients who may be
      at risk of complication from testing. In general, the previous recommendation of
      waiting for 6&emsp14;weeks after surgical procedures or medical complications
      before performing lung function can often now be reduced to <3&emsp14;weeks with
      modern less invasive surgical techniques.

PMID- 21954036
TI  - Prospective diagnostic performance evaluation of single-voxel 1H MRS for typing
      and grading of brain tumours.
AB  - The purpose of this study was to evaluate whether single-voxel (1)H MRS could add
      useful information to conventional MRI in the preoperative characterisation of
      the type and grade of brain tumours. MRI and MRS examinations from a prospective
      cohort of 40 consecutive patients were analysed double blind by radiologists and
      spectroscopists before the histological diagnosis was known. The spectroscopists
      had only the MR spectra, whereas the radiologists had both the MR images and
      basic clinical details (age, sex and presenting symptoms). Then, the radiologists
      and spectroscopists exchanged their predictions and re-evaluated their initial
      opinions, taking into account the new evidence. Spectroscopists used four
      different systems of analysis for (1)H MRS data, and the efficacy of each of
      these methods was also evaluated. Information extracted from (1)H MRS
      significantly improved the radiologists' MRI-based characterisation of grade IV
      tumours (glioblastomas, metastases, medulloblastomas and lymphomas) in the cohort
      [area under the curve (AUC) in the MRI re-evaluation 0.93 versus AUC in the MRI
      evaluation 0.85], and also of the less malignant glial tumours (AUC in the MRI re
      evaluation 0.93 versus AUC in the MRI evaluation 0.81). One of the MRS analysis
      systems used, the INTERPRET (International Network for Pattern Recognition of
      Tumours Using Magnetic Resonance) decision support system, outperformed the
      others, as well as being better than the MRI evaluation for the characterisation
      of grade III astrocytomas. Thus, preoperative MRS data improve the radiologists'
      performance in diagnosing grade IV tumours and, for those of grade II-III, MRS
      data help them to recognise the glial lineage. Even in cases in which their
      diagnoses were not improved, the provision of MRS data to the radiologists had no
      negative influence on their predictions.

PMID- 21954035
TI  - Outer hair cell-specific prestin-CreERT2 knockin mouse lines.
AB  - Outer hair cells (OHCs) in the cochlea are crucial for the remarkable hearing
      sensitivity and frequency tuning. To understand OHC physiology and pathology, it
      is imperative to use mouse genetic tools to manipulate gene expression
      specifically in OHCs. Here, we generated two prestin knockin mouse lines: (1) the
      prestin-CreERT2 line, with an internal ribosome entry site-CreERT2-FRT-Neo-FRT
      cassette inserted into the prestin locus after the stop codon, and (2) the
      prestin-CreERT2-NN line, with the FRT-Neo-FRT removed subsequently. We
      characterized the inducible Cre activity of both lines by crossing them with the
      reporter lines CAG-eGFP and Ai6. Cre activity was induced with tamoxifen at
      various postnatal ages and only detected in OHCs, resembling the endogenous
      prestin expression pattern. Moreover, prestin-CreERT2+/-(heterozygotes) and
      +/+(homozygotes) as well as prestin-CreERT2-NN+/-mice displayed normal hearing.
      These two prestin-CreERT2 mouse lines are therefore useful tools to analyze gene
      function in OHCs in vivo.

PMID- 21954037
TI  - Gene delivery methods in cardiac gene therapy.
AB  - Gene therapy for the treatment of heart failure is emerging as a
      multidisciplinary field demonstrating advances with respect to identifying key
      signaling pathways, modernized vector creation and delivery technologies.
      Although these discoveries offer significant progress, selecting optimal methods
      for the vector delivery remains a key component for efficient cardiac gene
      therapy to validate the targets in rodent models and to test clinically relevant
      ones in pre-clinical models. Although the goals of higher transduction efficiency
      and cardiac specificity can be achieved with several delivery methods, the
      invasiveness and patient safety remain unclear for clinical application. In this
      review, we discuss various features of the currently available vector delivery
      methods for cardiac gene therapy.

PMID- 21954038
TI  - Nickel-mediated cycloaddition by two sequential C-H activations.

PMID- 21954039
TI  - Incorporation of spiroxanthene units in blue-emitting oligophenylene frameworks:
      a new molecular design for OLED applications.
AB  - We report herein the incorporation of xanthenyl units into two extended pi
      conjugated phenylene systems, namely indenofluorene and pentaphenylene. Thus,
      dispiroxanthene-indenofluorene (DSX-IF) and dispiroxanthene-ladderpentaphenylene
      (DSX-LPP) have been designed and synthesized through short and efficient
      synthetic approaches. These two molecules possess a 3pi-2-spiro architecture (3pi
      systems/2-spiro bridges), in which two xanthenyl cores are spirolinked to a pi
      conjugated backbone either indenofluorene for DSX-IF or pentaphenylene for DSX
      LPP. The structural, electrochemical, and photophysical properties of these
      blue/violet emitters have been studied in detail and compared to those of their
      'all carbon' analogues with spirofluorenyl cores instead of spiroxanthenyl cores,
      namely dispirofluorene-indenofluorene (DSF-IF) and dispirofluorene
      ladderpentaphenylene (DSF-LPP), previously reported in the literature. Finally,
      the application of DSX-IF and DSX-LPP as new light-emitting materials in nondoped
      organic light emitting diodes is reported. A detailed optical study of the
      different electroluminescence spectra is notably presented, with an emphasis 1)
      on the origin of the low-energy emission band observed in the case of DSX-LPP and
      2) on the unexpected optical contribution of the well-known hole-transporting
      layer NPB (N,N'-di(naphtyl)-N,N'-diphenyl(1,1'-biphenyl)-4,4'-diamine).

PMID- 21954040
TI  - Pediatric regional examination of the musculoskeletal system: a practice- and
      consensus-based approach.
AB  - OBJECTIVE: Competent examination of the pediatric musculoskeletal (MSK) system is
      a vital component of clinical assessment of children with MSK presentations. The
      aim was to develop a regional MSK examination for school-age children that is age
      appropriate and reflects clinical practice. METHODS: Qualitative and quantitative
      analyses involving video observation of clinical examination technique,
      systematic review, and expert consensus were employed to reveal descriptions,
      frequencies, and variations in technique for joint regions in various clinical
      scenarios. Systematic review and data from clinical observation were combined
      with feedback from a group of pediatric MSK experts through a web-based survey.
      All results were collated and discussed by consensus development groups to derive
      the pediatric Regional Examination of the Musculoskeletal System (pREMS).
      RESULTS: A total of 48 pediatric MSK expert clinicians were involved to derive
      pREMS. Systematic review revealed a paucity of evidence about regional pediatric
      MSK examination. Video observations of MSK examinations (a total of 2,901
      maneuvers) performed by pediatric MSK experts (n = 11 doctors and 8 therapists)
      of 89 school-age children attending outpatient clinics in 7 UK pediatric
      rheumatology centers were followed by semistructured interviews with 14 of 19
      clinicians. Video observation showed variation in examination techniques, most
      frequently at the hip and knee in the context of mechanical and inflammatory
      clinical scenarios. CONCLUSION: pREMS is the first practice- and consensus-based
      regional pediatric MSK examination for school-age children. The structured
      approach is an important step toward improved pediatric MSK clinical skills
      relevant to clinical training.

PMID- 21954041
TI  - Expression of immunoreactivity of nuclear findings by p53 and cyclin a in
      endometrial cytology: Comparison with endometrial glandular and stromal breakdown
      and endometrioid adenocarcinoma grade 1.
AB  - It is well known that "condensed cluster of stromal cells (CCSC)" and
      "metaplastic clumps with irregular protrusion (MCIP)" in endometrial glandular
      and stromal breakdown (EGBD) cases may simulate "clumps of cancer cells (CCC)" in
      endometrioid adenocarcinoma grade 1 (G1), leading to difficulty in cytological
      interpretation. The aim of this study was undertaken to clarify the cytological
      immunoreactivity of nuclear findings about CCSC and MCIP which may be recognized
      in EGBD cases by using p53 protein and cyclin A in liquid-based cytologic (LBC)
      preparations. The material consists of cytologic smears of 20 cases of EGBD and
      20 cases of G1 for which histopathological diagnosis was obtained by endometrial
      curettage at the JA Suzuka General Hospital. The evaluation of immunoreactivity
      was performed by using the intensity of nuclear staining and the nuclear labeling
      index (N-LI). The intensity of nuclear staining was scored as negative (0), weak
      (1), moderate (2), or strong (3). The N-LI was scored as less than 10% (0), from
      10 to 25% (1), from 26 to 50% (2), or greater than 50% (3). The final score was
      calculated of the addition of both partial scores. Results are as follows: As for
      the p53 protein immunoreactivity, CCC (2.4 +/- 1.4) was a significantly higher
      value in comparison with CCSC (0) and MCIP (0.8 +/- 0.4), respectively. As for
      the cyclin A immunoreactivity, CCC (2.8 +/- 1.1) was a significantly higher value
      in comparison with CCSC (0) and MCIP (0.6 +/- 0.5), respectively. CCSC and MCIP
      in EGBD are misunderstood as cellular atypia and structural atypia on occasion;
      but, as for results of the immunoreactivity scores of p53 protein and cyclin A in
      our study, it seemed that those biochemical characters proved that the biological
      activity level was low (or degenerative). The results of the current study
      demonstrated that the cytological immunoreactivity of nuclear findings by p53 and
      cyclin A appear to be more useful for the LBC assessment of endometrial lesions,
      especially for the discrimination of EGBD and G1.

PMID- 21954042
TI  - Sensitivity of pink salmon (Oncorhynchus gorbuscha) embryos to weathered crude
      oil.

PMID- 21954044
TI  - Synthesis and antioxidant activity of substituted-1,3,2-diazaphosphole 1-oxides.
AB  - Synthesis of 1-substituted-1,3,2-diazaphosphole 1-oxides (3a-l) were accomplished
      via a two-step process. It involves the preparation of diazaphospholo 1-oxide
      monochloride intermediate (2) and its subsequent reaction with phenols/amino acid
      esters in dry THF in the presence of triethylamine at 40-45 degrees C. The
      structures of newly synthesized compounds were characterized by spectral and
      elemental analysis. The title compounds were evaluated for their in-vitro
      antioxidant properties.

PMID- 21954046
TI  - MR spectroscopy of the human prostate using surface coil at 3 T: metabolite
      ratios, age-dependent effects, and diagnostic possibilities.
AB  - PURPOSE: To measure prostate spectra of healthy volunteers using a surface coil,
      to demonstrate age-dependent effects, and to investigate diagnostic possibilities
      for prostate cancer detection. MATERIALS AND METHODS: Single-voxel and 2D
      magnetic resonance spectroscopic imaging (MRSI) spectra of 51 healthy volunteers
      with biopsy-proven prostate carcinoma of 20 patients for comparison were measured
      and processed using the LCModel. The mean normalized spectra and mean metabolite
      to-citrate intensity ratios were computed. RESULTS: Metabolite-to-citrate ratios
      of healthy volunteers were lower in the older group (>51 years) than in the
      younger group (<45 years). The peripheral zone (PZ) revealed a lower metabolite
      to-citrate intensity ratio than the central gland (CG). Age-related differences
      in metabolite-to-citrate ratio were insignificant in the voxels with
      predominantly CG tissue, whereas significant differences were found in the PZ.
      Sensitivity in detecting prostate cancer by single-voxel spectroscopy (SVS) and
      2D MRSI was 75% and 80%, respectively. CONCLUSION: SVS and 2D MRSI of the
      prostate at 3 T, using a surface coil, are useful in situations when insertion of
      the endorectal coil into the rectum is difficult or impossible. Our findings of
      age-dependent effects may be of importance for the analysis of patient spectra.

PMID- 21954047
TI  - Mesoporous titanium dioxide coating for metallic implants.
AB  - A bioactive mesoporous titanium dioxide (MT) coating for surface drug delivery
      has been investigated to develop a multifunctional implant coating, offering
      quick bone bonding and biological stability. An evaporation induced self-assembly
      (EISA) method was used to prepare a mesoporous titanium dioxide coating of the
      anatase phase with BET surface area of 172 m(2)/g and average pore diameter of
      4.3 nm. Adhesion tests using the scratch method and an in situ screw-in/screw-out
      technique confirm that the MT coating bonds tightly with the metallic substrate,
      even after removal from bone. Because of its high surface area, the bioactivity
      of the MT coating is much better than that of a dense TiO(2) coating of the same
      composition. Quick formation of hydroxyapatite (HA) in vitro can be related to
      enhance bonding with bone. The uptake of antibiotics by the MT coating reached
      13.4 mg/cm(3) within a 24 h loading process. A sustained release behavior has
      been obtained with a weak initial burst. By using Cephalothin as a model drug,
      drug loaded MT coating exhibits a sufficient antibacterial effect on the material
      surface, and within millimeters from material surface, against E.coli.
      Additionally, the coated and drug loaded surfaces showed no cytotoxic effect on
      cell cultures of the osteoblastic cell line MG-63. In conclusion, this study
      describes a novel, biocompatiblemesoporous implant coating, which has the ability
      to induce HA formation and could be used as a surface drug-delivery system.

PMID- 21954045
TI  - Individual-level factors in colorectal cancer screening: a review of the
      literature on the relation of individual-level health behavior constructs and
      screening behavior.
AB  - OBJECTIVE: Compliance with colorectal cancer screening recommendations requires
      considerable conscious effort on the part of the individual patient, making an
      individual's decisions about engagement in screening an important contributor to
      compliance or noncompliance. The objective of this paper was to examine the
      effectiveness of individual-level behavior theories and their associated
      constructs in accounting for engagement in colorectal cancer screening behavior.
      METHODS: We reviewed the literature examining constructs from formal models of
      individual-level health behavior as factors associated with compliance with
      screening for colorectal cancer. All published studies examining one or more
      constructs from the health belief model, theory of planned behavior,
      transtheoretical model, or social cognitive theory and their relation to
      screening behavior or behavioral intentions were included in the analysis.
      RESULTS: By and large, results of studies supported the theory-based predictions
      for the influence of constructs on cancer screening behavior. However, the
      evidence base for many of these relations, especially for models other than the
      health belief model, is quite limited. CONCLUSIONS: Suggestions are made for
      future research on individual-level determinants of colorectal cancer screening.

PMID- 21954048
TI  - Self-refocused adiabatic pulse for spin echo imaging at 7 T.
AB  - Spin echo pulse sequences are used to produce clinically important T(2) contrast.
      However, conventional 180 degrees  radiofrequency pulses required to generate a
      spin echo are highly susceptible to the B(1) inhomogeneity at high magnetic
      fields such as 7 Tesla (7 T), resulting in varying signal and contrast over the
      region of interest. Adiabatic 180 degrees  pulses may be used to replace
      conventional 180 degrees  pulses in spin echo sequences to provide greater
      immunity to the inhomogeneous B(1) field at 7 T. However, because the spectral
      profile of an adiabatic 180 degrees  pulse has nonlinear phase, pairs of these
      pulses are needed for proper refocusing, resulting in increased radiofrequency
      power deposition and long minimum echo times. We used the adiabatic Shinnar Le
      Roux method to generate a matched-phase adiabatic 90 degrees -180 degrees  pulse
      pair to obviate the need for a second adiabatic 180 degrees  pulse for phase
      refocusing. The pulse pair was then reformulated into a single self-refocused
      pulse to minimize the echo time, and phantom and in vivo experiments were
      performed to validate pulse performance. The self-refocused adiabatic pulse
      produced transmit profiles that were substantially more uniform than those
      achieved using a conventional spin echo sequence.

PMID- 21954049
TI  - Chronic restraint stress affects serotonin transporter uptake kinetics but not
      binding sites in the rat hippocampus.

PMID- 21954050
TI  - Exhaustive fluorine scanning toward potent p53-Mdm2 antagonists.

PMID- 21954051
TI  - Proteomic analysis of brain proteins in APP/PS-1 human double mutant knock-in
      mice with increasing amyloid beta-peptide deposition: insights into the effects
      of in vivo treatment with N-acetylcysteine as a potential therapeutic
      intervention in mild cognitive impairment and Alzheimer's disease.
AB  - Proteomics analyses were performed on the brains of wild-type (WT) controls and
      an Alzheimer's disease (AD) mouse model, APP/PS-1 human double mutant knock-in
      mice. Mice were given either drinking water or water supplemented with N
      acetylcysteine (NAC) (2 mg/kg body weight) for a period of five months. The time
      periods of treatment correspond to ages prior to Abeta deposition (i.e. 4-9
      months), resembling human mild cognitive impairment (MCI), and after Abeta
      deposition (i.e. 7-12 months), more closely resembling advancing stages of AD.
      Substantial differences exist between the proteomes of WT and APP/PS-1 mice at 9
      or 12 months, indicating that Abeta deposition and oxidative stress lead to
      downstream changes in protein expression. Altered proteins are involved in energy
      related pathways, excitotoxicity, cell cycle signaling, synaptic abnormalities,
      and cellular defense and structure. Overall, the proteomic results support the
      notion that NAC may be beneficial for increasing cellular stress responses in WT
      mice and for influencing the levels of energy- and mitochondria-related proteins
      in APP/PS-1 mice.

PMID- 21954052
TI  - Hydroxyapatite/polylactide biphasic combination scaffold loaded with
      dexamethasone for bone regeneration.
AB  - This study presents a novel design of a ceramic/polymer biphasic combination
      scaffold that mimics natural bone structures and is used as a bone graft
      substitute. To mimic the natural bone structures, the outside cortical-like
      shells were composed of porous hydroxyapatite (HA) with a hollow interior using a
      polymeric template-coating technique; the inner trabecular-like core consisted of
      porous poly(D,L-lactic acid) (PLA) that was loaded with dexamethasone (DEX) and
      was directly produced using a particle leaching/gas forming technique to create
      the inner diameter of the HA scaffold. It was observed that the HA and PLA parts
      of the fabricated HA/PLA biphasic scaffold contained open and interconnected pore
      structures, and the boundary between both parts was tightly connected without any
      gaps. It was found that the structure of the combination scaffold was analogous
      to that of natural bone based on micro-computed tomography analysis.
      Additionally, the dense, uniform apatite layer was formed on the surface of the
      HA/PLA biphasic scaffold through a biomimetic process, and DEX was successfully
      released from the PLA of the biphasic scaffold over a 1-month period. This
      release caused human embryonic palatal mesenchyme cells to proliferate,
      differentiate, produce ECM, and form tissue in vitro. Therefore, it was concluded
      that this functionally graded scaffold is similar to natural bone and represents
      a potential bone-substitute material.

PMID- 21954053
TI  - The pulmonary artery pulsatility index identifies severe right ventricular
      dysfunction in acute inferior myocardial infarction.
AB  - BACKGROUND: Right ventricular dysfunction (RVD) is a major cause of morbidity and
      mortality in the setting of acute inferior wall myocardial infarction (IWMI), and
      early detection may improve clinical outcomes. We defined a novel hemodynamic
      index, the pulmonary artery pulsatility index (PAPi), and explored whether the
      PAPi correlates with severe RVD in acute IWMI. METHODS: From 2008 to 2010, we
      identified 20 patients presenting with angiographically confirmed proximal right
      coronary artery occlusion and suspected RVD (sRVD) as defined by hemodynamic
      instability, profound bradycardia, or ST-elevation in lead V4R. Two controls
      groups were studied (1) 50 patients with nonobstructive coronary artery disease
      (Non-CAD) and (2) 14 patients presenting with acute coronary syndrome requiring
      left coronary stenting (ACS). Hemodynamic indices analyzed at the time of
      catheterization included: (1) the right atrial to pulmonary capillary wedge
      pressure ratio (RA:PCWP), (2) right ventricular stroke work (RVSW), and (3) the
      PAPi. Qualitative echocardiographic scores of RV systolic function were
      determined by two blinded investigators within 24 hr of catheterization. RESULTS:
      Among subjects with sRVD, 7 (35%) received a percutaneous RV support device
      (pRVSD) for medically refractory RV failure and 4 (20%) died prior to hospital
      discharge. Compared to Non-CAD and ACS controls, subjects with sRVD had a
      significantly lower PAPi (4.32 +/- 3.04 vs. 5.52 +/- 4.40 vs. 1.11 +/- 0.57,
      respectively, P < 0.01) and a higher RA:PCWP ratio (0.48 +/- 0.24 vs. 0.51 +/-
      0.26 vs. 0.81 +/- 0.30, respectively, P < 0.05). Both the PAPi and RA:PCWP ratios
      correlated significantly with RVSW and qualitative echocardiographic grading. The
      PAPi demonstrated the highest sensitivity (88.9%) and specificity (98.3%) for
      predicting in-hospital mortality and/or requirement of a pRVSD. Using ROC curve
      derived cut-points, a PAPi <= 0.9 provided 100.0% sensitivity and 98.3%
      specificity (C-statistic: 0.998) for predicting these outcomes, exceeding the
      predictive value of the RA:PCWP ratio or RVSW. CONCLUSIONS: The PAPi is a simple,
      invasive hemodynamic measure that may help identify high-risk patients with acute
      IWMI with severe RVD. Earlier identification of this high-risk population may
      improve clinical outcomes.

PMID- 21954056
TI  - Multiple impulse control disorders developing in Parkinson's disease after
      initiation of amantadine.

PMID- 21954054
TI  - Association between white matter microstructure, executive functions, and
      processing speed in older adults: the impact of vascular health.
AB  - Cerebral white matter damage is not only a commonly reported consequence of
      healthy aging, but is also associated with cognitive decline and dementia. The
      aetiology of this damage is unclear; however, individuals with hypertension have
      a greater burden of white matter signal abnormalities (WMSA) on MR imaging than
      those without hypertension. It is therefore possible that elevated blood pressure
      (BP) impacts white matter tissue structure which in turn has a negative impact on
      cognition. However, little information exists about whether vascular health
      indexed by BP mediates the relationship between cognition and white matter tissue
      structure. We used diffusion tensor imaging to examine the impact of vascular
      health on regional associations between white matter integrity and cognition in
      healthy older adults spanning the normotensive to moderate-severe hypertensive BP
      range (43-87 years; N = 128). We examined how white matter structure was
      associated with performance on tests of two cognitive domains, executive
      functioning (EF) and processing speed (PS), and how patterns of regional
      associations were modified by BP and WMSA. Multiple linear regression and
      structural equation models demonstrated associations between tissue structure, EF
      and PS in frontal, temporal, parietal, and occipital white matter regions. Radial
      diffusivity was more prominently associated with performance than axial
      diffusivity. BP only minimally influenced the relationship between white matter
      integrity, EF and PS. However, WMSA volume had a major impact on neurocognitive
      associations. This suggests that, although BP and WMSA are causally related,
      these differential metrics of vascular health may act via independent pathways to
      influence brain structure, EF and PS.

PMID- 21954055
TI  - Model-specific selection of molecular targets for heart failure gene therapy.
AB  - Heart failure (HF) is a complex multifaceted problem of abnormal ventricular
      function and structure. In recent years, new information has been accumulated
      allowing for a more detailed understanding of the cellular and molecular
      alterations that are the underpinnings of diverse causes of HF, including
      myocardial ischemia, pressure-overload, volume-overload or intrinsic
      cardiomyopathy. Modern pharmacological approaches to treat HF have had a
      significant impact on the course of the disease, although they do not reverse the
      underlying pathological state of the heart. Therefore gene-based therapy holds a
      great potential as a targeted treatment for cardiovascular diseases. Here, we
      survey the relative therapeutic efficacy of genetic modulation of beta-adrenergic
      receptor signaling, Ca(2+) handling proteins and angiogenesis in the most common
      extrinsic models of HF.

PMID- 21954057
TI  - Solvatochromic effects on the photoinduced charge-transfer states in donor
      acceptor substituted polydioctylfluorenes.
AB  - Polymer morphology affects quantum efficiency. The influence of polymer
      morphology on the emission from charge transfer states within donor-acceptor (D
      A) polydioctylfluorene derivatives is investigated. Two D-A copolymers,
      comprising one- and two-electron-donating triphenylamines substituted into the
      electron-accepting dioctylfluorene repeat unit were studied. Time-resolved
      emission spectra (with a resolution of 330 fs) in both liquid and glass phase
      isolate nuclear relaxation to the large-amplitude motion of the triphenylamine
      moiety about the single bond, analogous to the twisted intramolecular charge
      transfer (TICT) model. The charge separation in the polymers' emitting states is
      therefore increased, suggesting a potential approach to enhance quantum
      efficiency in devices otherwise limited by exciton recombination.

PMID- 21954058
TI  - Shape-memory surface with dynamically tunable nano-geometry activated by body
      heat.
AB  - Shape-memory surfaces with on-demand, tunable nanopatterns are developed to
      observe time dependent changes in cell alignment using temperature-responsive
      poly(epsilon-caprolactone) (PCL) films. Temporary grooved nanopatterns are easily
      programmed on the films and triggered to transition quickly to permanent surface
      patterns by the application of body heat. A time-dependent cytoskeleton
      remodeling is also observed under biologically relevant conditions.

PMID- 21954059
TI  - Discovery of the improved antagonistic prolactin variants by library screening.
AB  - Prolactin (PRL), a potent growth stimulator of the mammary epithelium, has been
      suggested to be a factor contributing to the development and progression of
      breast and prostate cancer. Several PRL receptor (PRLR) antagonists have been
      identified in the past decades, but their in vivo growth inhibitory potency was
      restricted by low receptor affinity, rendering them pharmacologically
      unattractive for clinical treatment. Thus, higher receptor affinity is essential
      for the development of improved PRLR antagonistic variants with improved in vivo
      potency. In this study, we generated Site 1 focused protein libraries of human
      G129R-PRL mutants and screened for those with increased affinity to the human
      PRLR. By combining the mutations with enhanced affinities for PRLR, we identified
      a novel G129R-PRL variant with mutations at Site 1 that render nearly 50-fold
      increase in the antagonistic potency in vitro.

PMID- 21954060
TI  - Design, synthesis, and antiproliferative activity of 3,4-diarylpyrazole-1
      carboxamide derivatives against melanoma cell line.
AB  - Synthesis of a new series of 3,4-diarylpyrazole-1-carboxamide derivatives is
      described. Their antiproliferative activity against A375P human melanoma cell
      line was tested and the effect of substituents on the diarylpyrazole scaffold was
      investigated. The biological results indicated that five synthesized compounds
      (Ig, Ii, IIc, IIg, and IIh) exhibited similar activity to Sorafenib. In addition,
      three compounds (IIa, IIb, and IIi) were more potent than Sorafenib. Among all of
      these derivatives, compound IIa which has dimethylamino and phenolic moieties
      showed the most potent antiproliferative activity against A375P human melanoma
      cell line. Virtual screening was carried out through docking of the most potent
      compound IIa into the domain of V600E-b-Raf and the binding mode was studied.

PMID- 21954061
TI  - Development of highly cytotoxic and actin-depolymerizing biotin derivatives of
      aplyronine A.
AB  - Tied up: a PEG-linked biotin derivative of marine macrolide aplyronine A (ApA) is
      shown to exhibit potent cytotoxicity and cause actin disassembly in tumor cells.
      This method of introducing a PEG linker at the end of the aliphatic tail should
      offer perspectives for developing and using versatile actin-targeting molecular
      probes. PEG=poly(ethylene glycol).

PMID- 21954062
TI  - Highly porous, water-soluble, superparamagnetic, and biocompatible magnetite
      nanocrystal clusters for targeted drug delivery.
AB  - Magnetic particles have become very promising materials for drug delivery.
      However, preparation of magnetite particles with high surface area,
      biocompatibility, strong magnetic response, and suitable particle size still
      remains a major challenge. In this report, magnetite nanocrystal clusters with
      high surface areas were fabricated through a solvothermal process by introducing
      ammonium acetate as a porogen and trisodium citrate as a surface modification
      agent. The porosity, which was controlled by the reactant concentration, has been
      investigated in detail. The surface area of the nanocrystal clusters was as high
      as 141 m(2) g(-1). Ibuprofen, as a model drug, was entrapped into the magnetite
      carriers. The interfacial interaction between the carboxylic groups on the drug
      molecules and the carboxylate groups on the carriers enhanced the loading
      efficiency. Low cytotoxicity in MCF-7 cell and in vitro constant drug release
      behavior combined with the high drug loading efficiency and high saturation
      magnetization values demonstrated the potential of the as-synthesized magnetite
      materials in targeted drug release systems.

PMID- 21954063
TI  - The oncocyte that went places: diagnosis with EUS-guided FNA.
AB  - Although uncommon, Hurthle cell neoplasms have a characteristic histologic and
      cytologic features which often aid in the diagnosis of these lesions. In fine
      needle aspiration biopsies, determining malignant potential on cytologic features
      is challenging unless other evidence of malignancy (such as metastases) are
      known. The role of EUS-guided FNA in diagnosing superior mediastinal masses has
      been described previously. It's role in evaluating subcarinal metastases from
      lung cancer primaries have also heen studied. However we describe metastatic
      thyroid Hurthle cell carcinoma to the subcarina diagnosed through EUS-guided FNA
      combining the unique cytologic features o Hurthle cell neoplasms and the
      versatility ofthe endoscopic ultrasound to reach a diagnosis in this unusual
      neoplasm.

PMID- 21954064
TI  - Deletion of a single allele of the Pex11beta gene is sufficient to cause
      oxidative stress, delayed differentiation and neuronal death in mouse brain.
AB  - Impaired neuronal migration and cell death are commonly observed in patients with
      peroxisomal biogenesis disorders (PBDs), and in mouse models of this diseases. In
      Pex11beta-deficient mice, we observed that the deletion of a single allele of the
      Pex11beta gene (Pex11beta(+/-) heterozygous mice) caused cell death in primary
      neuronal cultures prepared from the neocortex and cerebellum, although to a
      lesser extent as compared with the homozygous-null animals (Pex11beta(-/-) mice).
      In corresponding brain sections, cell death was rare, but differences between the
      genotypes were similar to those found in vitro. Because PEX11beta has been
      implicated in peroxisomal proliferation, we searched for alterations in
      peroxisomal abundance in the brain of heterozygous and homozygous Pex11beta-null
      mice compared with wild-type animals. Deletion of one allele of the Pex11beta
      gene slightly increased the abundance of peroxisomes, whereas the deletion of
      both alleles caused a 30% reduction in peroxisome number. The size of the
      peroxisomal compartment did not correlate with neuronal death. Similar to cell
      death, neuronal development was delayed in Pex11beta(+/-) mice, and to a further
      extent in Pex11beta(-/-) mice, as measured by a reduced mRNA and protein level of
      synaptophysin and a reduced protein level of the mature isoform of MAP2.
      Moreover, a gradual increase in oxidative stress was found in brain sections and
      primary neuronal cultures from wild-type to heterozygous to homozygous Pex11beta
      deficient mice. SOD2 was upregulated in neurons from Pex11beta(+/-) mice, but not
      from Pex11beta(-/-) animals, whereas the level of catalase remained unchanged in
      neurons from Pex11beta(+/-) mice and was reduced in those from Pex11beta(-/-)
      mice, suggesting a partial compensation of oxidative stress in the heterozygotes,
      but a failure thereof in the homozygous Pex11beta(-/-) brain. In conclusion, we
      report the alterations in the brain caused by the deletion of a single allele of
      the Pex11beta gene. Our data might lead to the reconsideration of the clinical
      treatment of PBDs and the common way of using knockout mouse models for studying
      autosomal recessive diseases.

PMID- 21954065
TI  - Testosterone treatment fails to accelerate disease in a transgenic mouse model of
      spinal and bulbar muscular atrophy.
AB  - Evidence from multiple animal models demonstrates that testosterone plays a
      crucial role in the progression of symptoms in spinal and bulbar muscular atrophy
      (SBMA), a condition that results in neurodegeneration and muscle atrophy in
      affected men. Mice bearing a transgene encoding a human androgen receptor (AR)
      that contains a stretch of 112 glutamines (expanded polyglutamine tract; AR112Q
      mice) reproduce several aspects of the human disease. We treated transgenic male
      AR112Q mice with testosterone for 6 months. Surprisingly, testosterone treatment
      of AR112Q males did not exacerbate the disease. Although transgenic AR112Q males
      exhibited functional deficits when compared with non-transgenics, long-term
      testosterone treatment had no effect on motor function. Testosterone treatment
      also failed to affect cellular markers of disease, including inclusion formation
      (the accumulation of large nuclear aggregates of mutant AR protein) and levels of
      unphosphorylated neurofilament heavy chain. These data suggest that the mechanism
      of disease in SBMA saturates at close to endogenous hormone levels and that
      individuals with SBMA who take, or have taken, testosterone for its putative
      therapeutic properties are unlikely to suffer adverse effects.

PMID- 21954066
TI  - Modeling psychiatric disorders through reprogramming.
AB  - Psychiatric disorders, including autism spectrum disorders and schizophrenia, are
      extremely heritable complex genetic neurodevelopmental disorders. It is now
      possible to directly reprogram fibroblasts from psychiatric patients into human
      induced pluripotent stem cells (hiPSCs) and subsequently differentiate these
      disorder-specific hiPSCs into neurons. This means that researchers can generate
      nearly limitless quantities of live human neurons with genetic backgrounds that
      are known to result in psychiatric disorders, without knowing which genes are
      interacting to produce the disease state in each patient. With these new human
      cell-based models, scientists can investigate the precise cell types that are
      affected in these disorders and elucidate the cellular and molecular defects that
      contribute to disease initiation and progression. Here, we present a short review
      of experiments using hiPSCs and other sophisticated in vitro approaches to study
      the pathways underlying psychiatric disorders.

PMID- 21954067
TI  - Animal models for Gaucher disease research.
AB  - Gaucher disease (GD), the most common lysosomal storage disorder (LSD), is caused
      by the defective activity of the lysosomal hydrolase glucocerebrosidase, which is
      encoded by the GBA gene. Generation of animal models that faithfully recapitulate
      the three clinical subtypes of GD has proved to be more of a challenge than first
      anticipated. The first mouse to be produced died within hours after birth owing
      to skin permeability problems, and mice with point mutations in Gba did not
      display symptoms correlating with human disease and also died soon after birth.
      Recently, conditional knockout mice that mimic some features of the human disease
      have become available. Here, we review the contribution of all currently
      available animal models to examining pathological pathways underlying GD and to
      testing the efficacy of new treatment modalities, and propose a number of
      criteria for the generation of more appropriate animal models of GD.

PMID- 21954068
TI  - Repletion of TNFalpha or leptin in calorically restricted mice suppresses post
      restriction hyperphagia.
AB  - The causes of post-restriction hyperphagia (PRH) represent a target for drug
      based therapies to prevent obesity. However, the factors causing PRH are poorly
      understood. We show that, in mice, the extent of PRH was independent of the time
      under restriction, but depended on its severity, suggesting that PRH was driven
      by signals from altered body composition. Signals related to fat mass were
      important drivers. Circulating levels of leptin and TNFalpha were significantly
      depleted following caloric restriction (CR). We experimentally repleted their
      levels to match those of controls, and found that in both treatment groups the
      level of PRH was significantly blunted. These data establish a role for TNFalpha
      and leptin in the non-pathological regulation of energy homeostasis. Signals from
      adipose tissue, including but not limited to leptin and TNFalpha, regulate PRH
      and might be targets for therapies that support people engaged in CR to reduce
      obesity.

PMID- 21954069
TI  - Quantitative dynamic contrast-enhanced MRI for mouse models using automatic
      detection of the arterial input function.
AB  - Dynamic contrast-enhanced MRI (DCE-MRI) is widely accepted for the evaluation of
      cancer. DCE-MRI, a noninvasive measurement of microvessel permeability, blood
      volume and blood flow, is extremely useful for understanding disease mechanisms
      and monitoring therapeutic responses in preclinical research. For the accurate
      quantification of pharmacokinetic parameters using DCE-MRI, determination of the
      arterial input function (AIF) from a large arterial vessel near the tumor is
      required. However, a manual determination of AIF in mouse MR images is often
      difficult because of the small spatial dimensions or the location of the tumor.
      In this study, we propose an algorithm for the automatic detection of AIF from
      mouse DCE-MR images using Kendall's coefficient of concordance. The proposed
      method was tested with computer simulations and then applied to tumor-bearing
      mice (n = 8). Results from computer simulations showed that the proposed
      algorithm is capable of categorizing simulated AIF signals according to their
      noise levels. We found that the resulting pharmacokinetic parameters computed
      from our method were comparable with those from the manual determination of AIF,
      with acceptable differences in K(trans) (5.14 +/- 3.60%), v(e) (6.02 +/- 3.22%),
      v(p) (5.10 +/- 7.05%) and k(ep) (5.38 +/- 4.72%). The results of the current
      study suggest the usefulness of an automatically defined AIF using Kendall's
      coefficient of concordance for quantitative DCE-MRI in mouse models for cancer
      evaluation.

PMID- 21954070
TI  - Identification of phenotypes with different clinical outcomes in knee
      osteoarthritis: data from the Osteoarthritis Initiative.
AB  - OBJECTIVE: To identify subgroups or phenotypes of knee osteoarthritis (OA)
      patients based on similarities of clinically relevant patient characteristics,
      and to compare clinical outcomes of these phenotypes. METHODS: Data from 842 knee
      OA patients of the Osteoarthritis Initiative were used. A cluster analysis method
      was performed, in which clusters were formed based on similarities in 4
      clinically relevant, easily available variables: severity of radiographic OA,
      lower extremity muscle strength, body mass index, and depression. Univariable and
      multivariable regression analyses were used to compare phenotypes on clinical
      outcomes (pain and activity limitations), taking into account possible
      confounders. RESULTS: Five phenotypes of knee OA patients were identified:
      "minimal joint disease phenotype," "strong muscle phenotype," "nonobese and weak
      muscle phenotype," "obese and weak muscle phenotype," and "depressive phenotype."
      The "depressive phenotype" and "obese and weak muscle phenotype" showed higher
      pain levels and more severe activity limitations than the other 3 phenotypes.
      CONCLUSION: Five phenotypes based on clinically relevant patient characteristics
      can be identified in the heterogeneous population of knee OA patients. These
      phenotypes showed different clinical outcomes. Interventions may need to be
      tailored to these clinical phenotypes.

PMID- 21954071
TI  - Biomaterial testing for covered stent membranes: evaluating thrombosis and
      restenosis potential.
AB  - Covered stents may be able to prevent both thrombosis and restenosis, but new
      mechanically suitable and biocompatible materials are needed before this
      treatment option can become a reality. Hydrophilic polyvinyl alcohol (PVA)
      cryogels have desirable mechanical properties for covered stent membranes and may
      be able to provide a physical barrier to restenosis with low thrombogenicity. An
      in vitro flow loop with porcine blood was used to compare thrombus formation on
      different blood-contacting biomaterials. PVA cryogels were found to maintain
      blood flow with low thrombogenicity and were significantly less thrombogenic than
      polyester (p < 0.05). The ability to prevent hyperplasic in-growth was evaluated
      using a modified Boyden chamber cellular migration assay. PVA cryogel membranes
      used as a physical barrier were found to nearly eliminate cellular migration (p <
      0.05) without cellular toxicity. Overall, this article demonstrates pivotal
      feasibility results for a covered stent membrane material that could prevent
      restenosis by means of a hydrogel barrier with low thrombogenicity.

PMID- 21954072
TI  - Genotoxicity of acute and chronic gamma-irradiation on zebrafish cells and
      consequences for embryo development.
AB  - The effects of radiation on biological systems have been studied for many years,
      and it is now accepted that direct damage to DNA from radiation is the triggering
      event leading to biological effects. In the present study, DNA damage induced by
      acute or chronic irradiation was compared at the cellular (zebrafish [Danio
      rerio] cell line ZF4) and developmental (embryo) levels. Zebrafish ZF4 cells and
      embryos (at 3 h postfertilization) were exposed within ranges of acute doses (0.3
      2 Gy/d) or chronic dose rates (0.1-0.75 Gy/d). DNA damage was assessed by
      immunodetection of gamma-H2AX and DNA-PK (DNA double-strand breaks) and the
      alkaline comet assay (DNA single-strand breaks). Zebrafish embryo development and
      DNA damage were examined after 120 h. At low doses, chronic irradiation induced
      more residual DNA damage than acute irradiation, but embryo development was
      normal. From 0.3 Gy, a hyper-radiosensitivity phenomenon compared to other
      species was shown for acute exposure with an increase of DNA damage, an
      impairment of hatching success, and larvae abnormalities. These results suggest a
      dose-dependent correlation between unrepaired DNA damage and abnormalities in
      embryo development, supporting the use of DNA repair proteins as predictive
      biomarkers of ionizing radiation exposure. This could have important implications
      for environmental protection.

PMID- 21954074
TI  - Fabrication and functionalization of hydrogels through "click" chemistry.
AB  - Hydrogels are crosslinked polymeric materials that play a vital role in many
      biomedical areas such as drug delivery, sensor technology, and tissue
      engineering. Increasing demand of these materials for such advanced applications
      has necessitated the development of hydrogels with complex chemical compositions
      such as incorporating small molecules and biomolecules that provide the
      functional attributes. This Focus Review highlights the tremendous impact of
      click chemistry on the design, synthesis, and functionalization of hydrogels. The
      high efficiency and fidelity of the click reactions have enabled rapid and
      modular synthesis of hydrogels with near-ideal network structures. Efficient
      incorporation of biomolecular building blocks, such as peptide sequences either
      during or after the fabrication of hydrogels, have been achieved through various
      click reactions. Utilization of these efficient reactions has led to the
      fabrication of many stimuli-responsive or 'smart' hydrogels in recent years.

PMID- 21954075
TI  - Click chemistry: 1,2,3-triazoles as pharmacophores.
AB  - The copper(I)-catalyzed 1,2,3-triazole-forming reaction between azides and
      terminal alkynes has become the gold standard of 'click chemistry' due to its
      reliability, specificity, and biocompatibility. Applications of click chemistry
      are increasingly found in all aspects of drug discovery; they range from lead
      finding through combinatorial chemistry and target-templated in vitro chemistry,
      to proteomics and DNA research by using bioconjugation reactions. The triazole
      products are more than just passive linkers; they readily associate with
      biological targets, through hydrogen-bonding and dipole interactions. The present
      review will focus mainly on the recent literature for applications of this
      reaction in the field of medicinal chemistry, in particular on use of the 1,2,3
      triazole moiety as pharmacophore.

PMID- 21954076
TI  - Cytocompatible poly(ethylene glycol)-co-polycarbonate hydrogels cross-linked by
      copper-free, strain-promoted click chemistry.
AB  - Strategies to encapsulate cells in cytocompatible three-dimensional hydrogels
      with tunable mechanical properties and degradability without harmful gelling
      conditions are highly desired for regenerative medicine applications. Here we
      reported a method for preparing poly(ethylene glycol)-co-polycarbonate hydrogels
      through copper-free, strain-promoted azide-alkyne cycloaddition (SPAAC) click
      chemistry. Hydrogels with varying mechanical properties were formed by "clicking"
      azido-functionalized poly(ethylene glycol)-co-polycarbonate macromers with
      dibenzocyclooctyne-functionalized poly(ethylene glycol) under physiological
      conditions within minutes. Bone marrow stromal cells encapsulated in these gels
      exhibited higher cellular viability than those encapsulated in photo-cross-linked
      poly(ethylene glycol) dimethacrylate. The precise control over the macromer
      compositions, cytocompatible SPAAC cross-linking, and the degradability of the
      polycarbonate segments make these hydrogels promising candidates for scaffold and
      stem cell assisted tissue repair and regeneration.

PMID- 21954077
TI  - Biofunctional silicon nanoparticles by means of thiol-ene click chemistry.
AB  - The preparation and characterization of butylene-terminated silicon nanoparticles
      (SiNPs) and their functionalization using thiol-ene chemistry is described, as
      well as the coupling of DNA strands. Bromide-terminated SiNPs were prepared by
      means of the oxidation of magnesium silicide and functionalized with butylene
      chains through treatment with the corresponding Grignard reagent. The successful
      coupling was confirmed by NMR and FTIR spectroscopy. TEM measurements revealed a
      silicon-core diameter of (2.4+/-0.5) nm. The fluorescence emission maximum is at
      lambda(max)=525 nm when excited at lambda(exc)=430 nm. The conjugation of these
      alkene-terminated SiNPs by means of thiol-ene chemistry is described for a
      variety of functional thiols. Efficient coupling was evidenced by NMR and FTIR
      spectroscopy. Moreover, the characteristic fluorescence properties of the SiNPs
      remained unaltered, thus demonstrating the value of this approach towards
      functional oxide-free SiNPs. Activation of the attached carboxylic acid moieties
      allowed for conjugation of NH(2)-terminated oligo-ssDNA (ss=single strand) to the
      SiNPs. Successful coupling was confirmed by a characteristic new UV absorption
      band at 260 nm, and by the still-present distinctive fluorescence of the SiNPs at
      525 nm. Gel electrophoresis confirmed coupling of 2 to 3 DNA strands onto the
      SiNPs, whereas no uncoupled DNA was observed.

PMID- 21954078
TI  - Ligand-assisted, copper(II) acetate-accelerated azide-alkyne cycloaddition.
AB  - Polytriazole ligands such as the widely used tris[(1-benzyl-1H-1,2,3-triazol-4
      yl)methyl]amine (TBTA), are shown to assist copper(II) acetate-mediated azide
      alkyne cycloaddition (AAC) reactions that involve nonchelating azides. Tris(2-{4
      [(dimethylamino)methyl]-1H-1,2,3-traizol-1-yl}ethyl)amine (DTEA) outperforms TBTA
      in a number of reactions. The satisfactory solubility of DTEA in a wide range of
      polar and nonpolar solvents, including water and toluene, renders it advantageous
      under copper(II) acetate-mediated conditions. The copper(II) acetate-mediated
      formation of the three triazolyl groups in a tris(triazolyl)-based ligand occurs
      sequentially with an inhibitory effect in the last step. The kinetic
      investigations of the ligand-assisted reactions reveal an interesting mechanistic
      dependence on the relative affinity of azide and alkyne to copper (II). In
      addition to expanding the scope of the copper(II) acetate-mediated AAC reactions
      to include nonchelating azides, this work offers evidence for the mechanistic
      synergy between the title reaction and the alkyne oxidative homocoupling
      reaction. The elucidation of the structural details of the polytriazole-ligand
      bound reactive species in copper(I/II)-mediated AAC reactions, however, awaits
      further characterization of the metal coordination chemistry of polytriazole
      ligands.

PMID- 21954080
TI  - Directing protons to the dioxygen ligand of a ruthenium(II) complex with pendent
      amines in the second coordination sphere.

PMID- 21954082
TI  - Dopamine agonist radioligand binds to both D2High and D2Low receptors, explaining
      why alterations in D2High are not detected in human brain scans.
AB  - The features of schizophrenia are consistent with increased sensitivity to
      endogenous dopamine. Animal models of schizophrenia reveal an increase in the in
      vitro proportion of striatal dopamine D2 receptors in the high-affinity state for
      dopamine (i.e., D2High), as measured by dopamine/[(3) H]domperidone competition.
      However, in vivo studies did not reveal the dopamine agonist [(11) C](+)PHNO to
      be elevated in amphetamine-sensitized rats. Also, no increase was found in the in
      vivo binding of [(11) C](+)PHNO in schizophrenia patients. This work was done to
      resolve the contradictory findings. It was found that the in vitro density of rat
      striatal D2 receptors was 18 pmol/g for [(3) H]raclopride and 12 pmol/g for [(3)
      H](+)PHNO; most of the latter sites disappeared in the presence of guanine
      nucleotide. Using 2 nM [(3) H](+)PHNO (K(d) of 0.72 nM at D2) to label D2
      receptors in the striata and the human D2 clone, 10 nM to 100 nM dopamine
      inhibited 10-20% of the [(3) H](+)PHNO bound, representing high-affinity binding
      of [(3) H](+)PHNO, with the remainder inhibited above 100 nM dopamine,
      representing low-affinity binding of [(3) H](+)PHNO. It was found that (+)PHNO
      and (-)NPA dissociated from the D2 clone with half-times of 96 and 600 s,
      respectively. These rates are slower than the reported sub-second dissociation of
      the G protein from a receptor, suggesting that these two ligands still occupy the
      D2Low receptor after the G protein has separated. Thus, the radio-agonist label
      for (+)PHNO is not selective for dopamine D2High receptors, but also binds to the
      D2Low state of the dopamine receptor.

PMID- 21954081
TI  - Stigma, perceived blame, self-blame, and depressive symptoms in men with
      colorectal cancer.
AB  - BACKGROUND: We measured the prevalence of stigma, self-blame, and perceived blame
      from others for their illness among men with colorectal cancer (CRC) and examined
      whether these factors were associated with depressive symptoms, independent of
      clinical and sociodemographic factors. METHODS: Self-administered questionnaires
      were returned in the fall of 2009 by 1109 eligible male US veterans who were
      diagnosed with CRC at any Veterans Affairs facility in 2008. Questionnaires
      assessed stigma, feelings of blame, and depressive symptoms as well as other
      facets of health, cancer characteristics, and quality and type of medical care.
      We report the prevalence of cancer stigma, self-blame, and perceived blame from
      others. We used multivariate linear regression to assess the association between
      these factors and a measure of depressive symptoms. Covariates included several
      measures of overall health, cancer progression, symptom severity, and
      sociodemographic factors. RESULTS: Thirty one percent of respondents endorsed at
      least one item in a measure of cancer stigma and 25% reported feeling that it was
      at least 'a little true' that they were to blame for their illness. All three
      independent variables were associated with depressive symptoms in bivariate
      models; cancer stigma and self-blame were significantly associated with
      depressive symptoms in the multivariate model. CONCLUSIONS: Cancer stigma and
      self-blame are problems for a significant minority of men with CRC and are
      independent predictors of depressive symptoms. They may represent an important
      source of stress in men with CRC.

PMID- 21954083
TI  - QUIPSS II with window-sliding saturation sequence (Q2WISE).
AB  - A series of periodic saturation pulses used to minimize the error caused by
      varying transit delays in assessing perfusion using quantitative imaging of
      perfusion using a single subtraction II with thin-slice TI(1) periodic saturation
      (Q2TIPS) increases the specific absorption rate. Quantitative imaging of
      perfusion using a single subtraction II with window-sliding saturation sequence
      (Q2WISE) has been developed, in which numerous thin saturation pulses are
      replaced by two thin pulses and one thick saturation pulse arranged in a window
      sliding manner within the labeling region to maintain a sharp slice profile while
      reducing specific absorption rate. Q2WISE essentially is a hybrid between Q2TIPS
      and quantitative imaging of perfusion using a single subtraction II for use in
      specific absorption rate intensive applications. Q2WISE was implemented on a 3 T
      MRI scanner to measure perfusion rates in the brain and kidneys of eight healthy
      volunteers and results were compared with those from Q2TIPS. Mean perfusion
      values of both methods for the brain (75 +/- 17 [Q2WISE] and 74 +/- 13 mL/100
      g/min [Q2TIPS]) and kidney (308 +/- 48 [Q2WISE] and 299 +/- 43 mL/100 g/min
      [Q2TIPS]) were in very good agreement.

PMID- 21954084
TI  - In vivo transport of Gd-DTPA(2-)  in human knee cartilage assessed by depth-wise
      dGEMRIC analysis.
AB  - PURPOSE: To investigate the transport of Gd-DTPA(2-) in different layers of
      femoral knee cartilage in vivo. MATERIALS AND METHODS: T(1) measurements (1.5
      Tesla) were performed in femoral knee cartilage of 23 healthy volunteers. The
      weight-bearing central cartilage was analyzed before contrast and at eight time
      points after an intravenous injection of Gd-DTPA(2-) : 12-60 min (4 volunteers)
      and 1-4 h (19 volunteers). Three regions of interest were segmented manually:
      deep, middle, and superficial. RESULTS: Before contrast injection, a depth-wise
      variation of T(1) was observed with 50% higher values in the superficial region
      compared with the deep region. In the deep region, the uptake of Gd-DTPA(2-) was
      not detected until 36 min and the concentration increased until 240 min, whereas
      in the superficial region, the uptake was seen already at 12 min and the
      concentration decreased after 180 min (P < 0.01). There was a difference between
      medial and lateral compartment regarding bulk, but not superficial Gd-DTPA(2-)
      concentration. The bulk gadolinium concentration was negatively related to the
      cartilage thickness (r = -0.68; P < 0.01). CONCLUSION: The depth-wise and
      thickness dependent variations in Gd-DTPA(2) transport influence the
      interpretation of bulk dGEMRIC analysis in vivo. In thick cartilage, incomplete
      penetration of Gd-DTPA(2) will yield a falsely too long T(1) .

PMID- 21954085
TI  - Solution-processable reduced graphene oxide as a novel alternative to PEDOT:PSS
      hole transport layers for highly efficient and stable polymer solar cells.

PMID- 21954086
TI  - Location of femoral artery access and correlation with vascular complications.

PMID- 21954087
TI  - Tagging cortical networks in emotion: a topographical analysis.
AB  - Viewing emotional pictures is associated with heightened perception and
      attention, indexed by a relative increase in visual cortical activity. Visual
      cortical modulation by emotion is hypothesized to reflect re-entrant connectivity
      originating in higher-order cortical and/or limbic structures. The present study
      used dense-array electroencephalography and individual brain anatomy to
      investigate functional coupling between the visual cortex and other cortical
      areas during affective picture viewing. Participants viewed pleasant, neutral,
      and unpleasant pictures that flickered at a rate of 10 Hz to evoke steady-state
      visual evoked potentials (ssVEPs) in the EEG. The spectral power of ssVEPs was
      quantified using Fourier transform, and cortical sources were estimated using
      beamformer spatial filters based on individual structural magnetic resonance
      images. In addition to lower-tier visual cortex, a network of occipito-temporal
      and parietal (bilateral precuneus, inferior parietal lobules) structures showed
      enhanced ssVEP power when participants viewed emotional (either pleasant or
      unpleasant), compared to neutral pictures. Functional coupling during emotional
      processing was enhanced between the bilateral occipital poles and a network of
      temporal (left middle/inferior temporal gyrus), parietal (bilateral parietal
      lobules), and frontal (left middle/inferior frontal gyrus) structures. These
      results converge with findings from hemodynamic analyses of emotional picture
      viewing and suggest that viewing emotionally engaging stimuli is associated with
      the formation of functional links between visual cortex and the cortical regions
      underlying attention modulation and preparation for action.

PMID- 21954088
TI  - Autologous fibrin scaffolds cultured dermal fibroblasts and enriched with
      encapsulated bFGF for tissue engineering.
AB  - Autologous fibrin scaffolds (AFSs) enriched with cells and specific growth
      factors represent a promising biocompatible scaffold for tissue engineering.
      Here, we analyzed the in vitro behavior of dermal fibroblasts (DFs) (cellular
      attachment, distribution, viability and proliferation, histological and
      immunohistochemical changes), comparing AFS with and without alginate
      microcapsules loaded with basic fibroblast growth factor (bFGF), to validate our
      scaffold in a future animal model in vivo. In all cases, DFs showed good adhesion
      and normal distribution, while in scaffolds with bFGF at 14 days, the cell counts
      detected in proliferation and viability assays were greatly improved, as was the
      proliferative state, and there was a decrease in muscle specific actin expression
      and collagen synthesis in comparison with the scaffolds without bFGF. In
      addition, the use of plasma without fibrinogen concentration methods, together
      with the maximum controlled release of bFGF at 14 days, favored cell
      proliferation. To conclude, we have been able to create an AFS enriched with
      fully functional DFs and release-controlled bFGF that could be used in multiple
      applications for tissue engineering.

PMID- 21954089
TI  - High frequency and reduced penetrance of LRRK2 G2019S mutation among Parkinson's
      disease patients in Cantabria (Spain).
AB  - The frequency and penetrance of the LRRK2 G2019S mutation varies considerably in
      different Parkinson disease (PD) populations. This information is essential both
      for clinical purposes and genetic counseling. The objective of this study was to
      estimate the prevalence and penetrance of the G2019S mutation of the LRRK2 gene
      in a small region in northern Spain (Cantabria). The G2019S mutation was tested
      in 367 consecutive patients with PD attended as outpatients in a tertiary
      Hospital in Northern Spain, and 126 at-risk family members of probands were also
      investigated for G2019S mutation and disease status. The gene penetrance was
      estimated in terms of cumulative age-specific incidence of PD by the Kaplan-Meier
      method. Thirty-two PD patients (8.7%) carried the G2019S mutation. Penetrance
      estimation of the G2019S mutation was 2% at 50 years, 12% at 60 years, 26% at 70
      years, and 47% at 80 years. The frequency of the G2019S mutation of the LRRK2
      gene in PD patients from Cantabria is among the highest reported so far after
      North African Arabs and Ashkenazi Jews. At the age of 80 years only one-half of
      G2019S mutation carriers manifest motor symptoms of PD.

PMID- 21954090
TI  - Endonucleases: tools to correct the dystrophin gene.
AB  - BACKGROUND: Various endonucleases can be engineered to induce double-strand
      breaks (DSBs) in chosen DNA sequences. These DSBs are spontaneously repaired by
      nonhomologous-end-joining, resulting in micro-insertions or micro-deletions
      (INDELs). We detected, characterized and quantified the frequency of INDELs
      produced by one meganuclease (MGN) targeting the RAG1 gene, six MGNs targeting
      three introns of the human dystrophin gene and one pair of zinc finger nucleases
      (ZFNs) targeting exon 50 of the human dystrophin gene. The experiments were
      performed in human cells (i.e. 293 T cells, myoblasts and myotubes). METHODS: To
      analyse the INDELs produced by the endonucleases the targeted region was
      polymerase chain reaction amplified and the amplicons were digested with the
      Surveyor enzyme, cloned in bacteria or deep sequenced. RESULTS: Endonucleases
      targeting the dystrophin gene produced INDELs of different sizes but there were
      clear peaks in the size distributions. The positions of these peaks were similar
      for MGNs but not for ZFNs in 293 T cells and in myoblasts. The size of the INDELs
      produced by these endonucleases in the dystrophin gene would have permitted a
      change in the reading frame. In a subsequent experiment, we observed that the
      frequency of INDELs was increased by re-exposition of the cells to the same
      endonuclease. CONCLUSIONS: Endonucleases are able to: (i) restore the normal
      reading of a gene with a frame shift mutation; (ii) delete a nonsense codon; and
      (iii) knockout a gene. Endonucleases could thus be used to treat Duchenne
      muscular dystrophy and other hereditary diseases that are the result of a
      nonsense codon or a frame shift mutation.

PMID- 21954091
TI  - A small molecule modulates circadian rhythms through phosphorylation of the
      period protein.

PMID- 21954093
TI  - Hydrogen-bonding-induced chirality organization and stabilization of redox
      species of polyaniline-unit molecules by introduction of amino acid pendant
      groups.
AB  - The chirality organization of polyaniline-unit molecules was achieved by the
      introduction of amino acid pendant groups through intramolecular hydrogen
      bonding, which plays an important role in the stabilization of the chirality
      organized redox species. Another interesting feature of the synthesized
      polyaniline-unit molecules is the luminescent switching properties based on the
      redox states of the phenylenediamine moiety.

PMID- 21954092
TI  - Economic comparison of diagnostic antibody production in perfusion stirred tank
      and in hollow fiber bioreactor processes.
AB  - The total operating costs of small-scale monoclonal antibody production were
      calculated for two different upstream options and general downstream procedure
      based on protein A chromatography. The upstream options were a spin-filter
      equipped stirred-tank bioreactor (STR) and a hollow fiber bioreactor (HFB). Both
      the bioreactors were operated in perfusion mode. The total operating costs of the
      processes were 6,900 ?/g for STR option and 6,400 ?/g for the HFB option. In the
      both systems, the costs were dominated by expenses derived from the downstream
      section (almost 80%) that was almost identical in the both systems. In the
      upstream section, the investment depreciation was the largest cost item. The
      lower total costs of the HFB option were a result of lower investment costs and
      more concentrated product that led into savings also in downstream section. This
      study brings out the HFB as on viable alternative for stirred-tank bioreactor,
      especially in small-scale diagnostic monoclonal antibody production.

PMID- 21954094
TI  - Exchange-mediated contrast agents for spin-lock imaging.
AB  - Measurements of relaxation rates in the rotating frame with spin-locking
      techniques are sensitive to substances with exchanging protons with appropriate
      chemical shifts. The authors develop a novel approach to exchange-rate selective
      imaging based on measured T(1rho) dispersion with applied locking field strength,
      and demonstrate the method on samples containing the X-ray contrast agent Iohexol
      with and without cross-linked bovine serum albumin. T(1rho) dispersion of water
      in the phantoms was measured with a Varian 9.4-T magnet by an on-resonance spin
      locking pulse with fast spin-echo readout, and the results used to estimate
      exchange rates. The Iohexol phantom alone gave a fitted exchange rate of ~1 kHz,
      bovine serum albumin alone was ~11 kHz, and in combination gave rates in between.
      By using these estimated rates, we demonstrate how a novel spin-locking imaging
      method may be used to enhance contrast due to the presence of a contrast agent
      whose protons have specific exchange rates.

PMID- 21954095
TI  - Differences in two-photon and one-photon absorption profiles induced by vibronic
      coupling: the case of dioxaborine heterocyclic dye.
AB  - A theoretical study of a dioxaborine heterocyclic compound in solution provides a
      case study for an analysis of the effects induced by the so-called Herzberg
      Teller (HT) vibronic coupling on the one-(OPA) and two-photon absorption (TPA)
      spectra. For TPA, the HT vibronic coupling induces differences in the shapes of
      the absorption band. The study highlights the importance of vibronic coupling as
      a potentially important mechanism in absorption spectroscopy, able to explain
      differences in the OPA/TPA spectra.

PMID- 21954096
TI  - MRI texture analysis of femoral neck: Detection of exercise load-associated
      differences in trabecular bone.
AB  - PURPOSE: To assess the ability of co-occurrence matrix-based texture parameters
      to detect exercise load-associated differences in MRI texture at the femoral neck
      cross-section. MATERIALS AND METHODS: A total of 91 top-level female athletes
      representing five differently loading sports and 20 referents participated in
      this cross-sectional study. Axial T1-weighted FLASH and T2*-weighted MEDIC
      sequence images of the proximal femur were obtained with a 1.5T MRI. The femoral
      neck trabecular bone at the level of the insertion of articular capsule was
      divided manually into regions of interest representing four anatomical sectors
      (anterior, posterior, superior, and inferior). Selected co-occurrence matrix
      based texture parameters were used to evaluate differences in apparent trabecular
      structure between the exercise loading groups and anatomical sectors of the
      femoral neck. RESULTS: Significant differences in the trabecular bone texture,
      particularly at the superior femoral neck, were observed between athletes
      representing odd-impact (soccer and squash) and high-magnitude exercise loading
      (power-lifting) groups and the nonathletic reference group. CONCLUSION: MRI
      texture analysis provides a quantitative method for detecting and classifying
      apparent structural differences in trabecular bone that are associated with
      specific exercise loading.

PMID- 21954097
TI  - Is the treatment of hepatocellular carcinoma on the waiting list necessary?

PMID- 21954098
TI  - Characterization of worn alumina hip replacement prostheses.
AB  - Alumina hip replacement prostheses have been analyzed following in vitro
      simulated microseparation. The worn surfaces of the alumina acetabular cup and
      femoral head were investigated using scanning electron microscopy (SEM) and
      atomic force microscopy (AFM) which identified four different wear zones. Focused
      ion beam (FIB) cross-sectioning was used to section the worn surface and produce
      3D reconstructions of the subsurface damage. This showed that the subsurface
      fracture was predominantly intergranular, with occasional intragranular fracture.
      Significantly, in all cases, fracture was restricted to the outer layer of
      grains. The wear mechanisms leading to the generation of the stripe wear region
      on the worn alumina hip prostheses are proposed and microseparation is believed
      to play a critical role.

PMID- 21954099
TI  - Complementary non-culprit revascularization during ST-elevation myocardial
      infarction...get to know your patient first to the editor.

PMID- 21954101
TI  - Morphology control of polymer particles in ethylene/carbon monoxide
      copolymerization.

PMID- 21954100
TI  - Atlantoepistrophic magnetic resonance imaging involvement in early rheumatoid
      arthritis: an aggressive tight control therapy not fully arresting the disease.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is the most common inflammatory disorder
      affecting the cervical spine. The purpose of this study was to characterize the
      atloaxial involvement with magnetic resonance imaging (MRI) in patients with
      early RA at the moment of diagnosis and after 18 months of a tight control
      therapy. METHODS: Twenty consecutive patients with early RA without cervical
      symptoms and 20 healthy controls were enrolled. The patients underwent unenhanced
      and enhanced gadolinium MRI study of the upper cervical spine at diagnosis and
      after 18 months of therapy. The presence of pannus tissue at MRI was considered
      active synovitis. RESULTS: Five (25%) of the 20 patients presented craniocervical
      involvement with active synovitis at MRI. At onset, patients with cervical
      involvement presented higher levels of erythrocyte sedimentation rate, a higher
      swollen joint count, and a higher Disease Activity Score in 44 joints level. All
      5 patients (100%) with cervical involvement presented already peripheral
      erosions. After 18 months, 1 of 5 patients with atloepistrophic synovial
      involvement at baseline presented complete regression of the enhancement of
      synovial periodontoid process, and 1 presented a decrease of this enhancement.
      None of the patients developed erosive process at the odontoid. The only patient
      with complete regression of the enhancement presented a very early disease (<3
      months). CONCLUSION: Our study demonstrates involvement of the atloaxial junction
      in 25% of early RA patients, in particular in patients with active and erosive
      arthritis. An early diagnosis and aggressive treatment with a combination
      therapy, aiming for remission, does not always reduce atlantoaxial synovitis.

PMID- 21954102
TI  - A comparison of data quality and practicality of online versus postal
      questionnaires in a sample of testicular cancer survivors.
AB  - OBJECTIVE: We aimed to compare data quality from online and postal questionnaires
      and to evaluate the practicality of these different questionnaire modes in a
      cancer sample. METHODS: Participants in a study investigating the psychosocial
      sequelae of testicular cancer could choose to complete a postal or online version
      of the study questionnaire. Data quality was evaluated by assessing sources of
      nonobservational errors such as participant nonresponse, item nonresponse and
      sampling bias. Time taken and number of reminders required for questionnaire
      return were used as indicators of practicality. RESULTS: Participant nonresponse
      was significantly higher among participants who chose the postal questionnaire.
      The proportion of questionnaires with missing items and the mean number of
      missing items did not differ significantly by mode. A significantly larger
      proportion of tertiary-educated participants and managers/professionals completed
      the online questionnaire. There were no significant differences in age,
      relationship status, employment status, country of birth or language spoken by
      completion mode. Compared with postal questionnaires, online questionnaires were
      returned significantly more quickly and required significantly fewer reminders.
      CONCLUSIONS: These results demonstrate that online questionnaire completion can
      be offered in a cancer sample without compromising data quality. In fact, data
      quality from online questionnaires may be superior due to lower rates of
      participant nonresponse. Investigators should be aware of potential sampling bias
      created by more highly educated participants and managers/professionals choosing
      to complete online questionnaires. Besides this issue, online questionnaires
      offer an efficient method for collecting high-quality data, with faster return
      and fewer reminders.

PMID- 21954103
TI  - Shape-controlled synthesis of Pt3Co nanocrystals with high electrocatalytic
      activity toward oxygen reduction.

PMID- 21954104
TI  - Cocaine induces the expression of MEF2C transcription factor in rat striatum
      through activation of SIK1 and phosphorylation of the histone deacetylase HDAC5.
AB  - Distinct forms of MEF2 transcription factor act as positive or negative
      regulators of dendritic spine formation, with MEF2C playing a key regulator role
      in synapse plasticity. We report here that acute cocaine treatment of rats
      induced the expression of MEF2C in the striatum through a recently discovered
      transduction pathway. Repeated injections were found to induce MEF2C to a lesser
      extent. The mechanism by which MEF2C was induced involves the subsequent
      activation of the salt-inducible kinase SIK1 and the phosphorylation of HDAC5, a
      member of the class IIa of HDACs. Cocaine activated SIK1 by phosphorylation on
      Thr-182 residue, which was accompanied by the nuclear import of the kinase. In
      the nuclear compartment, SIK1 then phosphorylated HDAC5 causing the shuttling of
      its phospho-form from the nucleus to the cytoplasm of striatal cells. Activation
      of SIK1 by cocaine was further validated by the phosphorylation of TORC1/3, which
      was followed by the shuttling of TORC proteins from the nucleus to the cytoplasm.
      Activation of MEF2C was assessed by measuring the expression of the MEF2C gene
      itself, since the gene is known to be under the control of its own product. Since
      MEF2C plays a key role in memory/learning processes, activation of this pathway
      by cocaine is probably involved in plasticity mechanisms whereby the drug
      establishes its long-term effects such as drug dependence.

PMID- 21954105
TI  - In vivo characterization of several rodent glioma models by 1H MRS.
AB  - The assessment of metabolites by (1)H MRS can provide information regarding
      glioma growth, and may be able to distinguish between different glioma models.
      Rat C6, 9 L/LacZ, F98 and RG2, and mouse GL261, cells were intracerebrally
      implanted into the respective rodents, and human U87 MG cells were implanted into
      athymic rats. Ethyl-nitrosourea induction was also used. Glioma metabolites [e.g.
      total choline (tCho), total creatine (tCr), N-acetylaspartate (NAA), lactate
      (Lac), glutamine (Gln), glutamate (Glu), aspartate (Asp), guanosine (Gua), mobile
      lipids and macromolecules (MMs)] were assessed from (1)H MRS using point-resolved
      spectroscopy (PRESS) [TE = 24 ms; TR = 2500 ms; variable pulse power and
      optimized relaxation delay (VAPOR) water suppression; 27-MUL and 8-MUL voxels in
      rats and mice, respectively] at 7 T. Alterations in metabolites (Totally
      Automatic Robust Quantitation in NMR, TARQUIN) in tumors were characterized by
      increases in lipids (Lip1.3: 8.8-54.5 mM for C6 and GL261) and decreases in NAA
      (1.3-2.0 mM for RG2, GL261 and C6) and tCr (0.8-4.0 mM for F98, RG2, GL261 and
      C6) in some models. F98, RG2, GL261 and C6 models all showed significantly
      decreased (p < 0.05) tCr, and RG2, GL261 and C6 models all exhibited
      significantly decreased (p < 0.05) NAA. The RG2 model showed significantly
      decreased (p < 0.05) Gln and Glu, the C6 model significantly decreased (p < 0.05)
      Asp, and the F98 and U87 models significantly decreased (p < 0.05) Gua, compared
      with controls. The GL261 model showed the greatest alterations in metabolites.
      (1)H MRS was able to differentiate the metabolic profiles in many of the seven
      rodent glioma models assessed. These models are considered to resemble certain
      characteristics of human glioblastomas, and this study may be helpful in
      selecting appropriate models.

PMID- 21954106
TI  - Functional connectivity changes in multiple sclerosis patients: a graph
      analytical study of MEG resting state data.
AB  - Multiple sclerosis (MS) is characterized by extensive damage in the central
      nervous system. Within this field, there is a strong need for more advanced,
      functional imaging measures, as abnormalities measured with structural imaging
      insufficiently explain clinicocognitive decline in MS. In this study we
      investigated functional connectivity changes in MS using resting-state
      magnetoencephalography (MEG). Data from 34 MS patients and 28 age and gender
      matched controls was assessed using synchronization likelihood (SL) as a measure
      of functional interaction strength between brain regions, and graph analysis to
      characterize topological patterns of connectivity changes. Cognition was assessed
      using extensive neuropsychological evaluation. Structural measures included brain
      and lesion volumes, using MRI. Results show SL increases in MS patients in theta,
      lower alpha and beta bands, with decreases in the upper alpha band. Graph
      analysis revealed a more regular topology in the lower alpha band in patients,
      indicated by an increased path length (lambda) and clustering coefficient
      (gamma). Attention and working memory domains were impaired, with decreased brain
      volumes. A stepwise linear regression model using clinical, MRI and MEG
      parameters as predictors revealed that only increases in lower alpha band gamma
      predicted impaired cognition. Cognitive impairments and related altered
      connectivity patterns were found to be especially predominant in male patients.
      These results show specific functional changes in MS as measured with MEG. Only
      changes in network topology were related to poorer cognitive outcome. This
      indicates the value of graph analysis beyond traditional structural and
      functional measures, with possible implications for diagnostic and/or prognostic
      purposes in MS.

PMID- 21954107
TI  - Characterization and behavior of anesthetic bioactive textile complex in vitro
      condition.
AB  - In this study, a bioactive complex containing nonwoven textile material
      (polypropilene (PP)/viscose), chitosan hydrogel, and lidocaine hydrochloride, was
      designed. The purpose of such biomedical textile was in the treatment of painful
      sites. Mercury intrusion porosimetry was used in order to estimate the influence
      of medical impregnation on porous structure of nonwoven material. It was
      estimated that more than 97% of pores in untreated nonwoven sample were larger
      than 15 MUm. Anesthetic treatment of nonwoven reduced total pore volume of
      ultramacropores and macropores, while total pore volume of mesopores slightly
      increased. Lidocaine hydrochloride release from the anesthetic/chitosan
      hydrogel/nonwoven complex was measured in vitro by Franz diffusion cell
      technique. Mathematical model was developed to estimate the release of the
      lidocaine from obtained bioactive textile material. The diffusive transport of
      lidocaine hydrochloride through three connected layers, i.e., polymer hydrogel,
      membrane, and solution is modeled based on Fick's second law. Taking all the
      relevant conditions, regarding this experiment, into consideration, the
      coefficient of lidocaine diffusion through the polymer hydrogel, as well as the
      concentration ratio parameter were determined by the mathematical model.

PMID- 21954108
TI  - Brain-derived neurotrophic factor produced by human umbilical tissue-derived
      cells is required for its effect on hippocampal dendritic differentiation.
AB  - The potential for nonembryonic cells to promote differentiation of neuronal cells
      has therapeutic implications for regeneration of neurons damaged by stroke or
      injury and avoids many ethical and safety concerns. The authors have assessed the
      capacity of human umbilical tissue-derived cells (hUTC) and human mesenchymal
      stromal cells (hMSC) to enhance differentiation of rodent hippocampal neurons. Co
      culture of hippocampal cells with hUTC or hMSC in transwell inserts for 3 days
      resulted in increase of several dendritic parameters including the number and
      length of primary dendrites. The effect of hUTC or hMSC on dendritic maturation
      was only apparent on neurons grown for 2 weeks in vitro prior to co-culture.
      Changes in dendritic morphology in the presence of hUTC were also accompanied by
      increased expression of the presynaptic marker synaptotagmin and the postsynaptic
      marker postsynaptic density protein 95 kDa (PSD95) suggesting that there may also
      be an increase in the number of synapses formed in the presence of hUTC. The
      effect of hUTC and hMSC on hippocampal cells in co-culture was comparable to
      those induced by treatment with recombinant human brain-derived neurotrophic
      factor (BDNF) implying that a similar factor may be released from hUTC or hMSC.
      Analysis of hUTC-conditioned medium by ELISA demonstrated that BDNF was indeed
      secreted. An antibody that blocks the actions of BDNF partially inhibited the
      actions of hUTC on dendritic morphology suggesting that BDNF is at least one of
      the factors secreted from the cells to promote dendritic maturation. These
      results indicate that hUTC secrete biologically active BDNF, which can affect
      dendritic morphology.

PMID- 21954109
TI  - Evidence of DNA transfer across a model membrane by a neutral amphiphilic block
      copolymer.
AB  - BACKGROUND: Neutral amphiphilic triblock copolymers have been shown to be
      efficient for gene transfection in vivo, especially by direct injection into the
      muscle. To contribute to a better understanding of the underlying mechanisms, in
      the present study, we investigated the properties of a poly(ethylene oxide-b-4
      vinylpyridine) diblock copolymer as vector for nucleic acid transfer, with the
      particular aim of shedding some light on a possible mechanism explaining the
      internalization of DNA by the transfected cells. METHODS: Complexation of plasmid
      DNA with the PEO-b-P4VP diblock copolymer was investigated by ethidium bromide
      exclusion and gel electrophoresis assays. Interaction of the copolymer with a
      lipid model membrane was evaluated by electrophysiological assays and
      quantification of plasmid DNA was performed by quantitative polymerase chain
      reaction. In vivo luciferase transfection assays were finally performed. RESULTS:
      The diblock copolymer was found to poorly interact with DNA up to a mass ratio
      (copolymer/DNA) as high as 150. At a concentration of 36 ug/ml, it induced the
      formation of mainly transient (but sometimes permanent) pores and the formation
      of those pores allowed the translocation of plasmid DNA across the model
      membrane. However, only low transgene expression was obtained; the luciferase
      levels observed with the diblock being of the same order of magnitude as those
      observed with the corresponding PEO and P4VP homopolymers. CONCLUSIONS: These
      results strongly suggest that gene transfection by neutral block copolymers may
      involve the formation of cellular pores; in addition, they also highlight that in
      vivo gene transfection requires the use of adequately soluble block copolymers.

PMID- 21954110
TI  - High sensitivity troponin T provides useful prognostic information in non-acute
      chest pain.
AB  - OBJECTIVE: To evaluate the prognostic value of high-sensitivity troponin T (hs
      cTnT) in patients who present to General Practitioners (GPs) with non-acute chest
      pain. DESIGN, SETTING AND PATIENTS: A total of 625 patients who were referred by
      their GPs to a regional Rapid Access Chest Pain Clinic in Tayside, Scotland were
      consented and recruited. Diamond-Forrester pretest probability of coronary artery
      disease (CAD) was used to select patients with intermediate and high-pretest
      probability. Hs-cTnT and B-type Natriuretic Peptide (BNP) were measured and final
      diagnosis recorded. Twelve-month follow-up for cardiac events and hospital
      admission data was collected. Sensitivity, specificity, positive predictive value
      and negative predictive value (NPV), for both prognosis and diagnosis, were
      produced using various pre-specified cut-off values for hs-cTnT and BNP. RESULTS:
      A total of 579 patients were included in the final analysis. Of these, 477 had
      intermediate/high-pretest probability of CAD. A total of 431 (90.4%) of patients
      had a hs-cTnT <=14 ng/l. In this study, hs-cTnT of 14 ng/l was the best cut-off
      for ruling out if a patient would have an admission for cardiac chest pain in the
      following 12 months (specificity 90%, NPV 91.4%). It performed well as a
      predictor of a subsequent negative diagnosis of cardiac chest pain with a
      specificity of 92.4% and NPV of 83.5%. CONCLUSIONS: Hs-cTnT, at the same level
      currently used in clinical practice as a diagnostic cut-off for myocardial
      infarction and acute coronary syndromes, is also a clinically-meaningful
      indicator for further 12-month cardiac chest pain hospital admissions in patients
      with non-acute chest pain referred to chest pain clinics by GPs.

PMID- 21954111
TI  - Calcium-alkali syndrome in post-surgical hypoparathyroidism.

PMID- 21954112
TI  - Metal-free synthesis of polysubstituted pyrroles by (diacetoxyiodo)benzene
      mediated cascade reaction of 3-alkynyl amines.

PMID- 21954113
TI  - The RNA-binding protein Unr prevents mouse embryonic stem cells differentiation
      toward the primitive endoderm lineage.
AB  - The maintenance of embryonic stem cells (ESCs) pluripotency depends on key
      transcription factors, chromatin remodeling proteins, and microRNAs. The roles of
      RNA-binding proteins are however poorly understood. We report that the
      cytoplasmic RNA-binding protein Unr prevents the differentiation of ESCs into
      primitive endoderm (PrE). We show that unr knockout (unr(-/-) ) ESCs
      spontaneously differentiate into PrE, and that Unr re-expression in unr(-/-) ESCs
      reverses this phenotype. Nevertheless, unr(-/-) ESCs retain pluripotency,
      producing differentiated teratomas, and the differentiated unr(-/-) ESCs
      coexpress the PrE inducer Gata6 and the pluripotency factors Oct4, Nanog, and
      Sox2. Interestingly, in the differentiated unr(-/-) ESCs, Nanog and Sox2 exhibit
      a dual nuclear and cytoplasmic localization. This situation, that has never been
      reported, likely reflects an early differentiation state toward PrE. Finally, we
      show that Unr destabilizes Gata6 mRNAs and we propose that the post
      transcriptional repression of Gata6 expression by Unr contributes to the
      stabilization of the ESCs pluripotent state.

PMID- 21954114
TI  - Solvent/base effects in the selective domino synthesis of phenanthridinones that
      involves high-valent palladium species: experimental and theoretical studies.
AB  - The domino reaction of o-bromobenzamides 1a-m in the presence of K(2)CO(3) and
      the [PdCl(2)(PPh(3))(2)] catalyst granted a selective access to phenanthridinones
      2 or to the new 1-carboxamide phenanthridinones 3 depending on the solvent, DMF
      or 1,4-dioxane, respectively. Investigations of the reaction parameters provided
      the first example of a direct correlation between the base dissociation and the
      solvent polarity on the selectivity observed. Moreover, mechanistic studies (NMR
      spectroscopy and ESI-MS monitoring) allowed us to characterize Pd(II)
      palladacycle 4 and biaryl species as common intermediates for these two domino
      processes. On that basis, C(sp(2))-C(sp(2)) bond formation is envisaged by
      generation of a Pd(IV) complex after oxidative addition of 1 into Pd(II)
      palladacycle 4, a rationale that is supported by DFT calculations. A general
      catalytic cycle is proposed to account for these observations.

PMID- 21954115
TI  - Hybrid coronary revascularization for the treatment of left main coronary
      stenosis: a feasibility study.
AB  - OBJECTIVE: To determine the feasibility of a hybrid coronary revascularization
      (HCR) approach for the treatment of left main (LM) coronary artery stenosis.
      BACKGROUND: The recommended therapy for significant LM stenosis is coronary
      artery bypass grafting (CABG). Percutaneous coronary intervention (PCI) of
      unprotected LM lesions is reserved for patients at high risk for complications
      with CABG. HCR in LM disease has not been studied. METHODS: Twenty-two
      consecutive patients with LM stenosis >70% underwent staged HCR. Following a
      robotic or thoracoscopic-assisted minimally invasive left internal mammary artery
      (LIMA) to left anterior descending artery (LAD) coronary bypass, PCI of the LM,
      and non-LAD targets was performed after angiographic confirmation of LIMA
      patency. Intravascular ultrasound confirmed optimal stent deployment. Thirty-day
      adverse outcomes and long term follow up was obtained. RESULTS: In the 22
      patients with LM lesions, 6 were ostial, 5 mid, and 11 distal. LIMA patency was
      FitzGibbon A in all cases. LM stenting was successful in all patients with drug
      eluting stents (DES) placed in 21 of 22 cases. Three patients underwent stent
      implantation in the right coronary artery. There were no 30-day major adverse
      cardiac or cerebrovascular events. At a mean of 38.8 +/- 22 months postprocedure,
      21 patients were alive without reintervention; one death occurred at 454 days.
      CONCLUSIONS: HCR for LM coronary disease is a feasible alternative to CABG and
      unprotected LM PCI. This approach combines the long-term durability of a LIMA-LAD
      bypass with the less invasive option of PCI in non-LAD targets with DES.

PMID- 21954116
TI  - Live imaging of endogenous periodic tryptophan protein 2 gene homologue during
      zebrafish development.
AB  - Yeast Periodic tryptophan protein 2 gene (Pwp2) is involved in ribosome
      biogenesis and has been implicated in regulation of the cell cycle in yeast.
      Here, we report a zebrafish protein-trap line that produces fluorescently tagged
      Periodic tryptophan protein 2 gene homologue (Pwp2h) protein, which can be
      dynamically tracked in living fish at subcellular resolution. We identified both
      full-length zebrafish Pwp2h and a short variant. The expression results show that
      Pwp2h is present in numerous sites in the early developing embryo, but later is
      restricted to highly proliferative regions, including the forebrain ventricular
      zone and endoderm-derived organs in the early larval stage. At the subcellular
      level, Pwp2h protein appears to be localized to the region of the nucleolus
      consistent with its presumed function in ribosomal RNA synthesis. This Pwp2h
      protein trap line offers a powerful tool to study the link between ribosome
      biogenesis and cell cycle progression during vertebrate development.

PMID- 21954117
TI  - Basis-set quality and basis-set bias in molecular property calculations.
AB  - Quality measures for Gaussian basis sets are proposed that are based on principal
      angles between the basis set and reference molecular orbitals. The principal
      angles are obtained from the cosine-sine (CS) decomposition of orthogonal
      matrices and yield detailed information about basis-set convergence with respect
      to different regions of space. Principal angles for occupied orbitals show
      excellent correlation with basis-set errors in ground-state energies.
      Furthermore, ground-state bias in finite basis sets can be estimated from the
      relation between principal angles for occupied and Rydberg orbitals. Ground-state
      bias is observed in basis sets including extensive diffuse augmentation and
      affects the quality of computed molecular response properties. Principal angles
      and ground-state bias are investigated for the H-Ne atoms and a series of
      diatomics using numerical Hartree-Fock calculations as a reference. Convergence
      of ground-state energies and static polarizabilities is studied for the
      hierarchies of correlation-consistent and Karlsruhe segmented def2 basis sets
      including different levels of diffuse augmentation.

PMID- 21954118
TI  - Is routine viral screening useful in patients with recent-onset polyarthritis of
      a duration of at least 6 weeks? Results from a nationwide longitudinal
      prospective cohort study.
AB  - OBJECTIVE: To study the contribution of routine viral screening tests in patients
      with early rheumatoid arthritis (RA) or a potential for progressing to RA.
      METHODS: Eight hundred thirteen patients with swelling of at least 2 joints for
      at least 6 weeks and a symptom duration of less than 6 months in the ESPOIR
      cohort were screened for parvovirus B19 (IgG and IgM anti-parvovirus B19
      antibodies), hepatitis B virus (HBV; hepatitis B surface antigen), hepatitis C
      virus (HCV; anti-HCV antibodies), and human immunodeficiency virus (HIV; anti-HIV
      1 and -2 antibodies). RESULTS: Parvovirus B19 testing was performed in 806
      patients and showed longstanding immunity in 574 (71.2%) and no antibodies in 223
      (27.7%). Among the 9 remaining patients (7 IgG positive/IgM positive, 1 IgG
      negative/IgM positive, and 1 IgG indeterminate/IgM positive), only 2 (0.25%; 95%
      confidence interval [95% CI] 0-0.99%) had a positive polymerase chain reaction
      test for parvovirus B19; these patients (women ages 34 and 40 years) had no
      extraarticular signs. HIV seroprevalence was 0.12% (n = 1 of 813; 95% CI 0.01
      0.8%) and HCV seroprevalence was 0.86% (n = 7 of 808, 95% CI 0.38-1.86%). HCV
      related arthritis was diagnosed in 4 patients (0.5%). HCV-seropositive patients
      had significantly higher transaminase levels than the other patients (P = 0.001),
      with no significant differences for the other laboratory data. HBV seroprevalence
      was 0.12% (n = 1 of 808; 95% CI 0.01-0.8%); the positive HBV status was known
      before study inclusion, and the patient had no diagnosis of HBV-related
      arthritis. Finally, routine viral testing identified 2 patients with parvovirus
      B19 infection and 3 with HBV infection (0.6%; 95% CI 0.2-1.5%). Cost was ?85.05
      per patient (total ?68,720). CONCLUSION: Routine serologic testing did not
      contribute substantially to the diagnosis in this context.

PMID- 21954120
TI  - Development of an "early warning" sensor for encrustation of urinary catheters
      following Proteus infection.
AB  - Biofilm formation in long-term urinary catheterized patients can lead to
      encrustation and blockage of urinary catheters with serious clinical
      complication. Catheter encrustation stems from infection with urease-producing
      bacteria, particularly Proteus mirabilis. Urease generates ammonia from urea, and
      the elevated pH of the urine results in crystallization of calcium and magnesium
      phosphates, which block the flow of urine. The aim of this research is to develop
      an "early warning" silicone sensor for catheter encrustation following bacterial
      infection of an in vitro bladder model system. The in vitro bladder model was
      infected with a range of urease positive and negative bacterial strains.
      Developed sensors enabled catheter blockage to be predicted ~17-24 h in advance
      of its occurrence. Signaling only occurred following infection with urease
      positive bacteria and only when catheter blockage followed. In summary, sensors
      were developed that could predict urinary catheter blockage in in vitro infection
      models. Translation of these sensors to a clinical environment will allow the
      timely and appropriate management of catheter blockage in long-term catheterized
      patients.

PMID- 21954119
TI  - Myocardial T1 mapping with MRI: comparison of look-locker and MOLLI sequences.
AB  - PURPOSE: To evaluate the relationship between "Look-Locker" (LL) and modified
      Look-Locker Inversion recovery (MOLLI) approaches for T1 mapping of the
      myocardium. MATERIALS AND METHODS: A total of 168 myocardial T1 maps using MOLLI
      and 165 maps using LL were obtained in human subjects at 1.5 Tesla. The T1 values
      of the myocardium were calculated before and at five time points after gadolinium
      administration. All time and heart rate normalizations were done. The T1 values
      obtained were compared to determine the absolute and bias agreement. RESULTS: The
      precontrast global T1 values were similar when measured by the LL and by MOLLI
      technique (mean, 1004.9 ms +/- 120.3 versus 1034.1 ms +/- 53.1, respectively, P =
      0.26). Postcontrast myocardial T1 time from LL was significantly longer than
      MOLLI from 5 to 25 min (mean difference, LL - MOLLI was +61.8 +/- 46.4 ms, P <
      0.001). No significant differences in T1 values were noted between long and short
      axis measurements for either MOLLI or LL. CONCLUSION: Postcontrast LL and MOLLI
      showed very good agreement, although LL values are higher than MOLLI. Precontrast
      T1 values showed good agreement, however LL has greater limits of agreement.
      Short and long axis planes can reliably assess T1 values.

PMID- 21954121
TI  - A mixed-solvent strategy for efficient exfoliation of inorganic graphene
      analogues.

PMID- 21954123
TI  - Isolation of a new strain of Picochlorum sp and characterization of its potential
      biotechnological applications.
AB  - Selection of new autochthon strains is necessary, and for the moment the best
      strategy, to find microalgae well adapted to the local climatological conditions
      able to simultaneously produce several compounds of biotechnological interest and
      grow at high rates. We describe the isolation and characterization of a new
      microalgal strain isolated from the marshlands of the Odiel River in the
      Southwest of Spain. The new microalga belongs to the genus Picochlorum, as
      deduced from the analysis of its 18S rRNA encoding gene, is able to grow at a
      high growth rate and thrive with adverse conditions. It has an appreciable
      constitutive level of lutein (3.5 mg g(-1) DW) and zeaxanthin (0.4 mg g(-1) DW)
      which is increased to 1.8 mg g(-1) DW at high light intensities. This strain is
      also characterized by a very low level of linolenic acid (3.8% of total fatty
      acids) and no polyunsaturated fatty acids with four or more double bonds.
      Although the total lipid content is not particularly high, 23% of the dry weight,
      its fatty acid profile makes of Picochlorum sp HM1 a promising candidate for
      biodiesel production, and the high content in the carotenoids lutein and
      zeaxanthin indicates that the microalga could also be a good source for natural
      eye vitamin supplements, which could be obtained as co-products.

PMID- 21954122
TI  - Nerve growth factor induces cell cycle arrest of astrocytes.
AB  - Neurotrophins can influence multiple cellular functions depending on the cellular
      context and the specific receptors they interact with. These neurotrophic factors
      have been extensively studied for their ability to support neuronal survival via
      Trk receptors and to induce apoptosis via the p75(NTR). However, the p75(NTR) is
      also detected on cell populations that do not undergo apoptosis in response to
      neurotrophins. In particular, the authors have detected p75(NTR) expression on
      astrocytes during development and after seizure-induced injury. In this study,
      the authors investigated the role of Nerve growth factor (NGF) in regulating
      astrocyte proliferation and in influencing specific aspects of the cell cycle.
      The authors have demonstrated that NGF prevents the induction of cyclins and
      their association with specific cyclin-dependent kinases, and thereby prevents
      progression through the G1 phase of the cell cycle. Since the authors have
      previously shown that p75(NTR) but not TrkA, is expressed in astrocytes, these
      data suggest that activation of p75(NTR) promotes withdrawal of astrocytes from
      the cell cycle, which may have important consequences during development and
      after injury.

PMID- 21954124
TI  - Phase contrast MRI is an early marker of micrometastatic breast cancer
      development in the rat brain.
AB  - The early growth of micrometastatic breast cancer in the brain often occurs
      through vessel co-option and is independent of angiogenesis. Remodeling of the
      existing vasculature is an important step in the evolution of co-opting
      micrometastases into angiogenesis-dependent solid tumor masses. The purpose of
      this study was to determine whether phase contrast MRI, an intrinsic source of
      contrast exquisitely sensitive to the magnetic susceptibility properties of
      deoxygenated hemoglobin, could detect vascular changes occurring independent of
      angiogenesis in a rat model of breast cancer metastases to the brain. Twelve nude
      rats were administered 10(6) MDA-MB-231BRL 'brain-seeking' breast cancer cells
      through intracardiac injection. Serial, multiparametric MRI of the brain was
      performed weekly until metastatic disease was detected. The results demonstrated
      that images of the signal phase (area under the receiver operating characteristic
      curve, 0.97) were more sensitive than T(2)* gradient echo magnitude images (area
      under the receiver operating characteristic curve, 0.73) to metastatic brain
      lesions. The difference between the two techniques was probably the result of the
      confounding effects of edema on the magnitude of the signal. A region of interest
      analysis revealed that vascular abnormalities detected with phase contrast MRI
      preceded tumor permeability measured with contrast-enhanced MRI by 1-2  weeks.
      Tumor size was correlated with permeability (R(2)= 0.23, p < 0.01), but phase
      contrast was independent of tumor size (R(2)= 0.03). Histopathologic analysis
      demonstrated that capillary endothelial cells co-opted by tumor cells were
      significantly enlarged, but less dense, relative to the normal brain vasculature.
      Although co-opted vessels were vascular endothelial growth factor-negative,
      vessels within larger tumor masses were vascular endothelial growth factor
      positive. In conclusion, phase contrast MRI is believed to be sensitive to
      vascular remodeling in co-opting brain tumor metastases independent of sprouting
      angiogenesis, and may therefore aid in preclinical studies of angiogenic
      independent tumors or in the monitoring of continued tumor growth following anti
      angiogenic therapy. Published 2011. This article is a US Government work and is
      in the public domain in the USA.

PMID- 21954125
TI  - Crosslinking of poly(L-lactide) nanofibers with triallyl isocyanutrate by gamma
      irradiation for tissue engineering application.
AB  - The radiation crosslinked poly(L-lactide) (PLLA) electrospun nanofibers have been
      developed with improved thermal stability and mechanical properties. Trially
      isocyanurate (TAIC) were added into PLLA solution at different weight ratios (1,
      3, and 5%) and electrospun into nanofibrous mats, the mats were then irradiated
      by gamma ray at different radiation doses (5, 10, and 25 kGy) to crosslink the
      PLLA chains. Their surface morphology, thermal properties, mechanical properties,
      and biodegradation properties were investigated and compared before and after
      gamma irradiation. Furthermore, the in vitro biocompatibilities were also
      evaluated by using mouse L929 fibroblasts. The results indicated that the
      efficient crosslinking networks can be generated when the TAIC content is higher
      than 3%. The thermal stability and tensile mechanical properties were
      significantly increased at higher irradiation dose of 10 and 25 kGy. However,
      radiation dose at 25 kGy have an adverse effect on the thermal stability of
      crosslinked samples due to thermal degradation induced by irradiation, the
      crosslinked samples irradiated at 10 kGy exhibited the best enzymatic
      degradation. The in vitro results also revealed that the crosslinked PLLA/TAIC
      composite nanofibers did not induce cytotoxic effects and are suitable for cell
      growth. Therefore, the crosslinked PLLA nanofibers are one of the promising
      materials for future tissue engineering applications.

PMID- 21954126
TI  - Co(1-x)S-graphene hybrid: a high-performance metal chalcogenide electrocatalyst
      for oxygen reduction.

PMID- 21954127
TI  - Virus-induced dilated cardiomyopathy is characterized by increased levels of
      fibrotic extracellular matrix proteins and reduced amounts of energy-producing
      enzymes.
AB  - The most relevant clinical phenotype resulting from chronic enteroviral
      myocarditis is dilated cardiomyopathy (DCM). Mice of the susceptible mouse strain
      A.BY/SnJ mimick well human DCM since they develop as a consequence of persistent
      infection and chronic inflammation a dilation of the heart ventricle several
      weeks after coxsackievirus B3 (CVB3) infection. Therefore, this model is well
      suited for the analysis of changes in the heart proteome associated with DCM.
      Here, we present a proteomic survey of the dilated hearts based on differential
      fluorescence gel electrophoresis and liquid chromatography-mass spectrometric
      centered methods in comparison to age-matched non-infected hearts. In total, 101
      distinct proteins, which belong to categories immunity and defense, cell
      structure and associated proteins, energy metabolism and protein
      metabolism/modification differed in their levels in both groups. Levels of
      proteins involved in fatty acid metabolism and electron transport chain were
      found to be significantly reduced in infected mice suggesting a decrease in
      energy production in CVB3-induced DCM. Furthermore, proteins associated with
      muscle contraction (MLRV, MLRc2, MYH6, MyBPC3), were present in significantly
      altered amounts in infected mice. A significant increase in the level of
      extracellular matrix proteins in the dilated hearts indicates cardiac remodeling
      due to fibrosis.

PMID- 21954128
TI  - Thermosensitive hydrogel for prolonged delivery of lentiviral vector expressing
      neurotrophin-3 in vitro.
AB  - BACKGROUND: The development of tissue engineering scaffolds for gene delivery has
      the potential to enhance gene transfer efficiency and safety via controlled
      temporal and spatial delivery. Lentiviral delivery can be carried out using the
      natural biopolymer thermoresponsive gel, chitosan/beta-glycerol phosphate (beta
      GP) as a carrier. METHODS: Three chitosan/beta-GP scaffolds were prepared with
      varying concentrations of chitosan and beta-GP to obtain a pH and gelation
      temperature suitable for in situ delivery. A lentiviral vector expressing either
      green fluorescent protein (Lenti GFP) or neurotrophin-3 (Lenti NT-3) was
      incorporated into the chitosan/beta-GP scaffolds and also into collagen 0.1% w/v
      (control). Viral elution medium was removed at various timepoints and added to
      the culture medium of pre-seeded HeLa or primary dorsal root ganglia (DRG) cells,
      respectively. GFP gene expression was quantified using fluorescence-activated
      cell sorting analysis. The effect of Lenti NT-3 was analyzed by measuring DRG
      neurite outgrowth. RESULTS: Collagen displayed its most significant elution of
      virus on day 1 and chitosan/beta-GP (with a final concentration of 2.17%
      chitosan) on day 3. CONCLUSIONS: The system shows promise for the in situ,
      thermoresponsive delivery of lentiviral vectors providing long-term gene
      expression for therapeutic factors to treat conditions such as injury to the
      nervous system.

PMID- 21954129
TI  - Photodissociation dynamics of benzaldehyde (C6H5CHO) at 266, 248, and 193 nm.
AB  - The photodissociation of gaseous benzaldehyde (C(6)H(5)CHO) at 193, 248, and 266
      nm using multimass ion imaging and step-scan time-resolved Fourier-transform
      infrared emission techniques is investigated. We also characterize the potential
      energies with the CCSD(T)/6-311+G(3df,2p) method and predict the branching ratios
      for various channels of dissociation. Upon photolysis at 248 and 266 nm, two
      major channels for formation of HCO and CO, with relative branching of 0.37:0.63
      and 0.20:0.80, respectively, are observed. The C(6)H(5)+HCO channel has two
      components with large and small recoil velocities; the rapid component with
      average translational energy of approximately 25 kJ mol(-1) dominates. The
      C(6)H(6)+CO channel has a similar distribution of translational energy for these
      two components. IR emission from internally excited C(6)H(5)CHO, nu(3) (v=1) of
      HCO, and levels v<=2, J<=43 of CO are observed; the latter has an average
      rotational energy of approximately 13 kJ mol(-1) and vibrational energy of
      approximately 6 kJ mol(-1). Upon photolysis at 193 nm, similar distributions of
      energy are observed, except that the C(6)H(5)+HCO channel becomes the only major
      channel with a branching ratio of 0.82+/-0.10 and an increased proportion of the
      slow component; IR emission from levels nu(1) (v=1) and nu(3) (v=1 and 2) of HCO
      and v<=2, J<=43 of CO are observed; the latter has an average energy similar to
      that observed in photolysis at 248 nm. The observed product yields at different
      dissociation energies are compared to statistical-theory predicted results based
      on the computed singlet and triplet potential-energy surfaces.

PMID- 21954130
TI  - Sperm competition differentially affects swimming velocity and size of
      spermatozoa from closely related muroid rodents: head first.
AB  - Sperm competition favours an increase in sperm swimming velocity that maximises
      the chances that sperm will reach the ova before rival sperm and fertilise.
      Comparative studies have shown that the increase in sperm swimming speed is
      associated with an increase in total sperm size. However, it is not known which
      are the first evolutionary steps that lead to increases in sperm swimming
      velocity. Using a group of closely related muroid rodents that differ in levels
      of sperm competition, we here test the hypothesis that subtle changes in sperm
      design may represent early evolutionary changes that could make sperm swim
      faster. Our findings show that as sperm competition increases so does sperm
      swimming speed. Sperm swimming velocity is associated with the size of all sperm
      components. However, levels of sperm competition are only related to an increase
      in sperm head area. Such increase is a consequence of an increase in the length
      of the sperm head, and also of the presence of an apical hook in some of the
      species studied. These findings suggest that the presence of a hook may modify
      the sperm head in such a way that would help sperm swim faster and may also be
      advantageous if sperm with larger heads are better able to attach to the
      epithelial cells lining the lower isthmus of the oviduct where sperm remain
      quiescent before the final race to reach the site of fertilisation.

PMID- 21954131
TI  - Long-term outcomes and costs of an integrated rehabilitation program for chronic
      knee pain: a pragmatic, cluster randomized, controlled trial.
AB  - OBJECTIVE: Chronic joint pain is a major cause of pain and disability. Exercise
      and self-management have short-term benefits, but few studies follow participants
      for more than 6 months. We investigated the long-term (up to 30 months) clinical
      and cost effectiveness of a rehabilitation program combining self-management and
      exercise: Enabling Self-Management and Coping of Arthritic Knee Pain Through
      Exercise (ESCAPE-knee pain). METHODS: In this pragmatic, cluster randomized,
      controlled trial, 418 people with chronic knee pain (recruited from 54 primary
      care surgeries) were randomized to usual care (pragmatic control) or the ESCAPE
      knee pain program. The primary outcome was physical function (Western Ontario and
      McMaster Universities Osteoarthritis Index [WOMAC] function), with a clinically
      meaningful improvement in physical function defined as a >=15% change from
      baseline. Secondary outcomes included pain, psychosocial and physiologic
      variables, costs, and cost effectiveness. RESULTS: Compared to usual care, ESCAPE
      knee pain participants had large initial improvements in function (mean
      difference in WOMAC function -5.5; 95% confidence interval [95% CI] -7.8, -3.2).
      These improvements declined over time, but 30 months after completing the
      program, ESCAPE-knee pain participants still had better physical function
      (difference in WOMAC function -2.8; 95% CI -5.3, -0.2); lower community-based
      health care costs (L-47; 95% CI L-94, L-7), medication costs (L-16; 95% CI L-29,
      L-3), and total health and social care costs (L-1,118; 95% CI L-2,566, L-221);
      and a high probability (80-100%) of being cost effective. CONCLUSION: Clinical
      and cost benefits of ESCAPE-knee pain were still evident 30 months after
      completing the program. ESCAPE-knee pain is a more effective and efficient model
      of care that could substantially improve the health, well-being, and independence
      of many people, while reducing health care costs.

PMID- 21954132
TI  - The resonance Raman spectra of spheroidene revisited with a first-principles
      approach.
AB  - The resonance Raman (RR) spectra of different configurations of spheroidene are
      calculated by means of quantum chemical methods to investigate the nature of the
      cis configuration of this carotenoid molecule in the photosynthetic reaction
      center (RC) of the purple bacterium Rhodobacter sphaeroides. For validation of
      our methodology, we also calculate the spectrum of the all-trans structure
      present in the light-harvesting complexes of this bacterium. While former
      theoretical resonance Raman studies only considered truncated models of
      spheroidene, we report on calculations employing the full pigment here. The
      calculated frequencies for the all-trans configuration are in good agreement with
      former experimental and simulated data. Among the possible cis structures, the
      15,15'-cis configuration shows a RR spectrum that is in best agreement with the
      experimental spectrum of spheroidene in the RC. In order to assess model
      truncation effects, we compare calculations for the full spheroidene molecule to
      those for the truncated model. While the main features can already be found in
      the latter, the full model leads to considerably different intensities in the
      region around 1150 cm(-1), which improve the agreement with experiment. A slight
      mismatch for the vibrational frequencies in the C=C stretch region is
      investigated by considering a model for spheroidene in the binding pocket
      comprising more than 500 atoms in total. The results do not lead to improved
      agreement with experiment, in contrast to the simpler strategy of introducing
      constraints in the structural optimization of a truncated spheroidene model. The
      calculated RR spectrum of the 13,14-cis configuration shows additional features
      which can also be identified in the experimental RR spectrum. This shows that the
      most likely cis structure is the 15,15'-cis configuration. Besides this, the
      13,14-cis configuration remains a candidate for an additional spheroidene
      structure in the RC of Rhodobacter sphaeroides mutant R26.

PMID- 21954133
TI  - Predictors of reintervention in neonates with critical pulmonary stenosis or
      pulmonary atresia with intact ventricular septum.
AB  - OBJECTIVES: Describe the short and midterm outcome and to determine the
      predictors of reintervention in neonates with critical pulmonary stenosis (PS) or
      pulmonary atresia with intact ventricular septum (PA/IVS). BACKGROUND: The
      transcatheter intervention for critical PS and PA/IVS resulted in improvement in
      the patient's survival and the quality of life. The procedure is not free of
      complications and there is still a significant rate of reintervention. METHOD:
      All neonates with critical PS or PA/IVS who underwent interventional cardiac
      catheterization between November 2004 and January 2009 were reviewed
      retrospectively. We performed a comparison between those who required
      reintervention and those who did not, to identify the predictors of
      reintervention. RESULTS: Forty-three neonates were included, 23 (53.5%) had
      critical PS and 20 (46.5%) had PA/IVS. Twenty-six patients (60%) were males, the
      mean age was 11 +/- 8 days, and the mean weight was 3.2 +/- 0.6 kg. Two patients
      died (4.6%). The mean follow-up period was 19 +/- 13 months for 42 patients.
      Fifteen patients (36%) required reintervention, 11 of them (73%) had PA/IVS, and
      4 (27%) had critical PS. Reintervention was more in patients with PA/IVS than
      those with critical PS (P = 0.003). Other predictors for reintervention included
      hospital stay >= 7.5 days (P = 0.001) and tricuspid valve regurgitation peak
      gradient in day one post first intervention (TR1) >= 43 mm Hg (P = 0.03).
      CONCLUSION: Interventional cardiac catheterization shows favorable outcome for
      patients with critical PS and PA/IVS. Predictors for reintervention included the
      diagnosis of PA/IVS, hospital stay >=7.5 days after first intervention and TR1
      gradient >= 43 mm Hg.

PMID- 21954134
TI  - Biomimetic mineralization of dentin induced by agarose gel loaded with calcium
      phosphate.
AB  - A novel biomimetic mineralization system was designed to induce a layer of
      hydroxyapatite on a demineralized dentin surface. This system was constructed as
      follows. A layer of 0.5% agarose gel containing 0.26M Na(2) HPO(4) was used to
      cover acid-etched dentin slices, followed by a layer of agarose gel without
      phosphate ions. Then a neutral 0.13M CaCl(2) solution was added onto the ion-free
      gel surface. The mineralization system (dentin-agarose gel containing phosphate
      ions-CaCl(2) solution) was kept in a water bath at 37 degrees C, and the gel and
      CaCl(2) solution were replaced at various intervals. The results showed that the
      deposited hydroxyapatite crystals densely packed to each other, completely
      covered the dentin surface, and occluded the dentinal tubules after 10 days of
      biomimetic mineralization in vitro. Therefore, this method may provide the
      experimental basis for dentin remineralization and for a new method to treat
      dentin hypersensitivity and dental caries.

PMID- 21954135
TI  - Model-based analysis on the relationship of signal quality to real-time
      extraction of information in bioprocesses.
AB  - Quality by design (QbD) is a current structured approach to design processes
      yielding a quality product. Knowledge and process understanding cannot be
      achieved without proper experimental data; hence requirements for measurement
      error and frequency of measurement of bioprocess variables have to be defined. In
      this contribution, a model-based approach is used to investigate impact factors
      on calculated rates to predict the obtainable information from real-time
      measurements (= signal quality). Measurement error, biological activity, and
      averaging window (= period of observation) were identified as biggest impact
      factors on signal quality. Moreover, signal quality has been set in context with
      a quantifiable measure using statistical error testing, which can be used as a
      benchmark for process analytics and exploitation of data. Results have been
      validated with data from an E. coli batch process. This approach is useful to get
      an idea which process dynamics can be observed with a given bioprocess setup and
      sampling strategy beforehand.

PMID- 21954136
TI  - Visual experience affects both behavioral and neuronal aspects in the individual
      life history of the desert ant Cataglyphis fortis.
AB  - The individual life history of the desert ant Cataglyphis fortis is characterized
      by a fast transition from interior tasks to mainly visually guided foraging.
      Previous studies revealed a remarkable structural synaptic plasticity in visual
      and olfactory input regions within the mushroom bodies of the ants' brain centers
      involved in learning and memory. Reorganization of synaptic complexes
      (microglomeruli) was shown to be triggered by sensory exposure rather than an
      internal program. Using video analyses at the natural nest site and activity
      recordings after artificial light treatments we investigated whether the ants get
      exposed to light before onset of foraging and whether this changes the ants'
      activity levels. We asked whether synaptic reorganization occurs in a similar
      time window by immunolabeling and quantification of pre- and postsynaptic
      compartments of visual and olfactory microglomeruli after periods of light
      exposure. Ants reverted back to dark nest conditions were used to investigate
      whether synaptic reorganization is reversible. The behavior analyses revealed
      that late-interior ants (diggers) are exposed to light and perform exploration
      runs up to 2 days before they start foraging. This corresponds well with the
      result that artificial light treatment over more than 2-3 days significantly
      increased the ants' locomotor activities. At the neuronal level, visual exposure
      of more than 1 day was necessary to trigger reorganization of microglomeruli, and
      light-induced changes were only partly reversible in the dark. We conclude that
      visual preexposure is an important and flexible means to prepare the ants' visual
      pathway for orientation capabilities essential during foraging.

PMID- 21954137
TI  - Analysis of Pax7 expressing myogenic cells in zebrafish muscle development,
      injury, and models of disease.
AB  - The transcription factor Pax7 is a marker and regulator of muscle progenitors and
      satellite cells that contribute to the embryonic development and postembryonic
      growth of skeletal muscle in vertebrates, as well as to its repair and
      regeneration. Here, we identify Pax7(+ve) myogenic cells in the zebrafish and
      characterize their behavior in postembryonic stages. Mononucleate Pax7(+ve) cells
      can first be found associated with myofibers at 72 hours post fertilization
      (hpf). To follow the behavior of muscle progenitor cells in vivo, we generated
      transgenic lines expressing fluorescent proteins under the control of the pax7a
      or pax3a promoters. We established an injury model using cardiotoxin injection
      and monitored cell proliferation and myogenic regulatory factor expression in
      myogenic precursors cells and muscle fibers after injury using proliferation
      markers and the transgenic lines. We also analyzed Pax7(+ve) cells in animals
      with dystrophic phenotypes and found an increased number compared with wild-type.

PMID- 21954138
TI  - Symbol nomenclature for representing glycan structures: Extension to cover
      different carbohydrate types.
AB  - This Viewpoint article addresses comments made on our original article describing
      a symbolic system for the depiction of N- and O-linked carbohydrate structures
      and proposes a method for extending the symbol set to include monosaccharides
      commonly found in carbohydrates present in bacteria and plants. As before, basic
      monosaccharides are shown by shape with one or more additions such as solid fill
      or additions of lines, crosses or dots to represent functional groups. The use of
      colour to differentiate constituent monosaccharides is avoided, thus enabling the
      system to be used in a variety of formats. Linkage and anomericity are shown by
      the angle and type of line connecting the symbols. In this extended version, new
      symbols are proposed for additional hexoses and it is proposed that pyranose and
      furanose forms of the monosaccharides could be shown by solid or broken outlines
      to the symbols. Conventions for depicting the presence of multiple functional
      groups such as deoxy-(NH(2))(2) are also discussed. It is hoped that these
      proposals will stimulate discussion so that a consensus can be reached as to how
      the glycobiology community can best convey complex information in a simple
      manner.

PMID- 21954139
TI  - Ionic-surfactant-coated Burkholderia cepacia lipase as a highly active and
      enantioselective catalyst for the dynamic kinetic resolution of secondary
      alcohols.

PMID- 21954140
TI  - Friedel-Crafts benzylation of activated and deactivated arenes.

PMID- 21954142
TI  - A ditopic fluorescence sensor for saccharides and mercury based on a boronic-acid
      receptor and desulfurisation reaction.
AB  - Two boron-contained fluorescent sensors, 1 and 2, based on coumarin have been
      prepared. The fluorescence response of the two systems was investigated with
      addition of saccharide and mercury ions. Sensor 2 behaves as a bifunctional
      fluorescent switch with chemical inputs of D-fructose and mercury ions.

PMID- 21954141
TI  - Development of a functional assessment scale for ambulatory boys with Duchenne
      muscular dystrophy.
AB  - BACKGROUND AND PURPOSE: The aims of this study were to develop a clinical
      assessment scale to measure functional ability in ambulant boys with Duchenne
      muscular dystrophy and to determine the reliability of the scale in multiple
      centres in the UK. METHODS: Focus groups and workshops were held with experienced
      paediatric neuromuscular physiotherapists to determine scale content. A manual
      was prepared with accompanying videos, and training sessions were conducted. A
      total of 17 physiotherapists from participating centres used the videos to
      determine inter-rater reliability. Five determined the intra-rater reliability.
      RESULTS: Strength of agreement for these groups based on total subject scores was
      very good (0.95 and >= 0.93 for consistency and absolute agreement,
      respectively). Test-retest ability was high, with perfect agreement between
      occasions for all but two items of the scale. CONCLUSIONS: Our study indicates
      that the North Star Ambulatory Assessment is practical and reliable. It takes
      only 10 minutes to perform and incorporates both universally used timed tests as
      well as levels of activities, which allow assessment of high-functioning boys
      with Duchenne muscular dystrophy.

PMID- 21954143
TI  - From micro to macro: access to long-range Li+ diffusion parameters in solids via
      microscopic (6, 7) Li spin-alignment echo NMR spectroscopy.
AB  - The development of highly conductive solids is a rapidly growing research area in
      materials science. In particular, the study of Li-ion conductors is driven by the
      ambitious effort to design powerful lithium-ion batteries. A deeper understanding
      of Li dynamics in solids requires the availability of a large set of
      complementary techniques to probe Li self-diffusion on different length and time
      scales. We report on (7)Li as well as (6)Li spin-alignment echo (SAE) nuclear
      magnetic resonance (NMR) spectroscopy, which is capable of probing long-range
      diffusion parameters from a microscopic, that is, atomic-scale, point of view. So
      far, variable-temperature SAE NMR spectroscopy has been applied to a number of
      polycrystalline and glassy Li-ion conductors. The materials investigated serve as
      model systems to unravel the interesting features of the technique in determining
      reliable Li jump rates and hopping activation energies. In particular, the latter
      are compared with those probed by macroscopic techniques such as dc-conductivity
      measurements that are sensitive to long-range translational motions.

PMID- 21954144
TI  - Thresholds in disease activity for switching biologics in rheumatoid arthritis
      patients: experience from a large U.S. cohort.
AB  - OBJECTIVE: To examine the threshold in disease activity associated with switching
      biologic treatment regimens in rheumatoid arthritis (RA) patients in real-world
      clinical practice. METHODS: Using data from a prospective observational North
      American cohort of RA patients through December 30, 2009, patients who initiated
      a new anti-tumor necrosis factor alpha (anti-TNFalpha) agent with >=6 months of
      followup were identified. Patients were classified as switchers or maintainers
      depending on whether they continued their anti-TNF treatment or switched
      (including discontinuation) within 12 months. Level of disease activity measured
      by the Clinical Disease Activity Index (CDAI) and Disease Activity Score in 28
      joints (DAS28) at the time of the switch (corresponding followup visit for
      maintainers) was examined and random-effect multivariable logistic regression was
      used to adjust for covariates. RESULTS: Mean age and RA duration among 1,549
      eligible patients were 56.1 and 9.6 years, respectively, 80% were women, 62% were
      initiating their first biologic, and 30% were initiating their second biologic.
      At the time of the switch, the median DAS28 and CDAI score were 3.1 and 8.4 among
      maintainers and 4.0 and 15.2 among switchers, respectively. Maintainers also
      experienced a greater amount of reduction in disease activity compared with
      switchers (CDAI: -7.7 versus -2.3, DAS28: -1.1 versus -0.3). The threshold to
      switch decreased over calendar time, with the greatest amount of reduction
      observed among patients with moderate disease activity. CONCLUSION: On average,
      physicians and patients were willing to continue biologic treatment for patients
      who were at or near low disease activity. The threshold to switch decreased over
      time, especially among partial responders.

PMID- 21954145
TI  - Intracardiac echocardiography and fluoroscopy guided percutaneous left
      ventricular pseudoaneurysm closure.
AB  - Left ventricular (LV) pseudoaneurysm is a rare complication after myocardial
      infarction and cardiac surgery. Standard treatment remains surgical correction;
      however, percutaneous closure has been attempted in high risk surgical patients.
      We report a case of three dimensional echocardiography and cardiac CT defined LV
      pseudoaneurysm which was closed percutaneously using intracardiac
      echocardiography (ICE) and fluoroscopy guidance. Appropriate planning and
      guidance proved essential to the procedure with an excellent outcome.
      Percutaneous closure of LV pseudoaneurysms is safe and feasible in high risk
      surgical patients and with appropriate imaging modalities may be an alternative
      to surgical correction.

PMID- 21954147
TI  - Ontogenetic development of an exceptionally preserved Devonian cartilaginous
      skeleton.
AB  - Cartilaginous vertebrate skeletons leave few records as fossils, unless
      mineralized. Here, we report outstanding preservation of early stages of
      cartilage differentiation, present in the Devonian vertebrate Palaeospondylus
      gunni. In large specimens of Palaeospondylus, enlarged, hypertrophic cell spaces
      (lacunae) are dominant in the cartilage matrix, each defined by thin mineralized
      matrix, where phosphorus and calcium co-occur. This is comparable to living
      endochondral cartilage, where cell hypertrophy and matrix mineralization mark the
      end of an ontogenetic process of cell growth and division before bone formation.
      New information from small individuals of Palaeospondylus demonstrates that the
      skeleton comprises mostly unmineralized organic matrix with fewer hypertrophic
      cell spaces, these occurring only in the central regions of each element. Only
      here has the surrounding matrix begun to mineralize, differing from the larger
      specimens in that phosphorus is dominant with little associated calcium at these
      earlier stages. This reflects cellular control of mineralization in living
      tissues through phosphate accumulation around hypertrophic cells, with later
      increase in calcium in the cartilaginous matrix. These features are always
      associated with endochondral bone development, but in the Palaeospondylus
      skeleton, this bone never develops. This skeletal state is thus far unique among
      vertebrates, with two alternative explanations: either later stages of
      endochondral bone development have been lost in Palaeospondylus, or, in a
      stepwise acquisition of the mineralized skeleton, these late stages have not yet
      evolved.

PMID- 21954146
TI  - Developing laryngeal muscle of Xenopus laevis as a model system: androgen-driven
      myogenesis controls fiber type transformation.
AB  - The developmental programs that contribute to myogenic stem cell proliferation
      and muscle fiber differentiation control fiber numbers and twitch type. In this
      study, we describe the use of an experimental model system-androgen-regulated
      laryngeal muscle of juvenile clawed frogs, Xenopus laevis-to examine the
      contribution of proliferation by specific populations of myogenic stem cells to
      expression of the larynx-specific myosin heavy chain isoform, LM. Androgen
      treatment of juveniles (Stage PM0) resulted in upregulation of an early (Myf-5)
      and a late (myogenin) myogenic regulatory factor; the time course of LM
      upregulation tracked that of myogenin. Myogenic stem cells stimulated to
      proliferate by androgen include a population that expresses Pax-7, a marker for
      the satellite cell myogenic stem cell population. Since androgen can switch
      muscle fiber types from fast to slow even in denervated larynges, we developed an
      ex vivo culture system to explore the relation between proliferation and LM
      expression. Cultured whole larynges maintain sensitivity to androgen, increasing
      in size and LM expression. Blockade of cell proliferation with cis-platin
      prevents the switch from slow to fast twitch muscle fibers as assayed by ATPase
      activity. Blockade of cell proliferation in vivo also resulted in inhibition of
      LM expression. Thus, both in vivo and ex vivo, inhibition of myogenic stem cell
      proliferation blocks androgen-induced LM expression and fiber type switching in
      juveniles.

PMID- 21954148
TI  - Patterning materials through viscoelastic flow and phase separation.

PMID- 21954149
TI  - Chiral nematic mesoporous carbon derived from nanocrystalline cellulose.

PMID- 21954151
TI  - What makes osteoarthritis painful? The evidence for local and central pain
      processing.
AB  - OA is a chronic arthritic disease characterized by pain, local tissue damage and
      attempts at tissue repair. Historically, cartilage damage was believed to be the
      hallmark of OA. However, since cartilage is an avascular, aneural tissue, the
      mechanisms of pain are likely to be complex and influenced by non-cartilaginous
      structures in the joint including the synovium, bone and soft tissue. Imaging
      studies reveal the presence of synovitis and bone marrow lesions that may mediate
      pain. The presence of local joint inflammation and altered cartilage and bone
      turnover in OA implicates a potential role for a range of molecular mediators in
      OA pain. Mechanisms of pain perception may include the activation and release of
      local pro-inflammatory mediators such as prostaglandins and cytokines accompanied
      by the destruction of tissue, which is mediated by proteases. However,
      clinically, there is often disparity between the degree of pain perception and
      the extent of joint changes in subjects with OA. Such observations have prompted
      work to investigate the mechanisms of central pain perception in OA. Functional
      MRI has identified multiple areas of the brain that are involved in OA pain
      processing. These data demonstrate that pain perception in OA is complex in being
      influenced by local factors and activation of central pain-processing pathways.
      In this review, we will discuss current concepts underlying the pathophysiology
      of pain perception in OA and suggest possible directions for the future
      management of pain in this condition based on recent clinical studies.

PMID- 21954150
TI  - Timescale analysis of rule-based biochemical reaction networks.
AB  - The flow of information within a cell is governed by a series of protein-protein
      interactions that can be described as a reaction network. Mathematical models of
      biochemical reaction networks can be constructed by repetitively applying
      specific rules that define how reactants interact and what new species are formed
      on reaction. To aid in understanding the underlying biochemistry, timescale
      analysis is one method developed to prune the size of the reaction network. In
      this work, we extend the methods associated with timescale analysis to reaction
      rules instead of the species contained within the network. To illustrate this
      approach, we applied timescale analysis to a simple receptor-ligand binding model
      and a rule-based model of interleukin-12 (IL-12) signaling in naive CD4+ T cells.
      The IL-12 signaling pathway includes multiple protein-protein interactions that
      collectively transmit information; however, the level of mechanistic detail
      sufficient to capture the observed dynamics has not been justified based on the
      available data. The analysis correctly predicted that reactions associated with
      Janus Kinase 2 and Tyrosine Kinase 2 binding to their corresponding receptor
      exist at a pseudo-equilibrium. By contrast, reactions associated with ligand
      binding and receptor turnover regulate cellular response to IL-12. An empirical
      Bayesian approach was used to estimate the uncertainty in the timescales. This
      approach complements existing rank- and flux-based methods that can be used to
      interrogate complex reaction networks. Ultimately, timescale analysis of rule
      based models is a computational tool that can be used to reveal the biochemical
      steps that regulate signaling dynamics.

PMID- 21954152
TI  - Review: in people with dementia, cholinesterase inhibitors may increase syncope
      and memantine may reduce fractures.

PMID- 21954153
TI  - Review: secretin is not effective for the treatment of children with autism
      spectrum disorders.

PMID- 21954154
TI  - Review: depot antipsychotics may reduce risk of relapse compared with oral
      antipsychotics in people with schizophrenia.

PMID- 21954155
TI  - Many people show poor adherence to their initial antipsychotic after first
      hospitalisation with schizophrenia.

PMID- 21954156
TI  - Review: motivational interviewing reduces substance use compared with no
      treatment in substance-dependent individuals.

PMID- 21954157
TI  - Intrinsic property of flavin mononucleotide controls its optical spectra in three
      redox states.

PMID- 21954158
TI  - Opaque7 encodes an acyl-activating enzyme-like protein that affects storage
      protein synthesis in maize endosperm.
AB  - In maize, a series of seed mutants with starchy endosperm could increase the
      lysine content by decreased amount of zeins, the main storage proteins in
      endosperm. Cloning and characterization of these mutants could reveal regulatory
      mechanisms for zeins accumulation in maize endosperm. Opaque7 (o7) is a classic
      maize starchy endosperm mutant with large effects on zeins accumulation and high
      lysine content. In this study, the O7 gene was cloned by map-based cloning and
      confirmed by transgenic functional complementation and RNAi. The o7-ref allele
      has a 12-bp in-frame deletion. The four-amino-acid deletion caused low
      accumulation of o7 protein in vivo. The O7 gene encodes an acyl-activating enzyme
      with high similarity to AAE3. The opaque phenotype of the o7 mutant was produced
      by the reduction of protein body size and number caused by a decrease in the
      alpha-zeins concentrations. Analysis of amino acids and metabolites suggested
      that the O7 gene might affect amino acid biosynthesis by affecting alpha
      ketoglutaric acid and oxaloacetic acid. Transgenic rice seeds containing RNAi
      constructs targeting the rice ortholog of maize O7 also produced lower amounts of
      seed proteins and displayed an opaque endosperm phenotype, indicating a conserved
      biological function of O7 in cereal crops. The cloning of O7 revealed a novel
      regulatory mechanism for storage protein synthesis and highlighted an effective
      target for the genetic manipulation of storage protein contents in cereal seeds.

PMID- 21954159
TI  - The conserved foot domain of RNA pol II associates with proteins involved in
      transcriptional initiation and/or early elongation.
AB  - RNA polymerase (pol) II establishes many protein-protein interactions with
      transcriptional regulators to coordinate different steps of transcription.
      Although some of these interactions have been well described, little is known
      about the existence of RNA pol II regions involved in contact with
      transcriptional regulators. We hypothesize that conserved regions on the surface
      of RNA pol II contact transcriptional regulators. We identified such an RNA pol
      II conserved region that includes the majority of the "foot" domain and
      identified interactions of this region with Mvp1, a protein required for sorting
      proteins to the vacuole, and Spo14, a phospholipase D. Deletion of MVP1 and SPO14
      affects the transcription of their target genes and increases phosphorylation of
      Ser5 in the carboxy-terminal domain (CTD). Genetic, phenotypic, and functional
      analyses point to a role for these proteins in transcriptional initiation and/or
      early elongation, consistent with their genetic interactions with CEG1, a
      guanylyltransferase subunit of the Saccharomyces cerevisiae capping enzyme.

PMID- 21954160
TI  - A method for inferring the rate of occurrence and fitness effects of advantageous
      mutations.
AB  - The distribution of fitness effects (DFE) of new mutations is of fundamental
      importance in evolutionary genetics. Recently, methods have been developed for
      inferring the DFE that use information from the allele frequency distributions of
      putatively neutral and selected nucleotide polymorphic variants in a population
      sample. Here, we extend an existing maximum-likelihood method that estimates the
      DFE under the assumption that mutational effects are unconditionally deleterious,
      by including a fraction of positively selected mutations. We allow one or more
      classes of positive selection coefficients in the model and estimate both the
      fraction of mutations that are advantageous and the strength of selection acting
      on them. We show by simulations that the method is capable of recovering the
      parameters of the DFE under a range of conditions. We apply the method to two
      data sets on multiple protein-coding genes from African populations of Drosophila
      melanogaster. We use a probabilistic reconstruction of the ancestral states of
      the polymorphic sites to distinguish between derived and ancestral states at
      polymorphic nucleotide sites. In both data sets, we see a significant improvement
      in the fit when a category of positively selected amino acid mutations is
      included, but no further improvement if additional categories are added. We
      estimate that between 1% and 2% of new nonsynonymous mutations in D. melanogaster
      are positively selected, with a scaled selection coefficient representing the
      product of the effective population size, N(e), and the strength of selection on
      heterozygous carriers of ~2.5.

PMID- 21954161
TI  - Dynamics of homology searching during gene conversion in Saccharomyces cerevisiae
      revealed by donor competition.
AB  - One of the least understood aspects of homologous recombination is the process by
      which the ends of a double-strand break (DSB) search the entire genome for
      homologous templates that can be used to repair the break. We took advantage of
      the natural competition between the alternative donors HML and HMR employed
      during HO endonuclease-induced switching of the budding yeast MAT locus. The
      strong mating-type-dependent bias in the choice of the donors is enforced by the
      recombination enhancer (RE), which lies 17 kb proximal to HML. We investigated
      factors that improve the use of the disfavored donor. We show that the normal
      heterochromatic state of the donors does not impair donor usage, as donor choice
      is not affected by removing this epigenetic silencing. In contrast, increasing
      the length of homology shared by the disfavored donor increases its use. This
      result shows that donor choice is not irrevocable and implies that there are
      several encounters between the DSB ends and even the favored donor before
      recombination is accomplished. The increase by adding more homology is not
      linear; these results can be explained by a thermodynamic model that determines
      the energy cost of using one donor over the other. An important inference from
      this analysis is that when HML is favored as the donor, RE causes a reduction in
      its effective genomic distance from MAT from 200 kb to ~20 kb, which we
      hypothesize occurs after the DSB is created, by epigenetic chromatin
      modifications around MAT.

PMID- 21954162
TI  - Differentiation of carbon dioxide-sensing neurons in Caenorhabditis elegans
      requires the ETS-5 transcription factor.
AB  - Many animals sense environmental gases such as carbon dioxide and oxygen using
      specialized populations of gas-sensing neurons. The proper development and
      function of these neurons is critical for survival, as the inability to respond
      to changes in ambient carbon dioxide and oxygen levels can result in reduced
      neural activity and ultimately death. Despite the importance of gas-sensing
      neurons for survival, little is known about the developmental programs that
      underlie their formation. Here we identify the ETS-family transcription factor
      ETS-5 as critical for the normal differentiation of the carbon dioxide-sensing
      BAG neurons in Caenorhabditis elegans. Whereas wild-type animals show acute
      behavioral avoidance of carbon dioxide, ets-5 mutant animals do not respond to
      carbon dioxide. The ets-5 gene is expressed in BAG neurons and is required for
      the normal expression of the BAG neuron gene battery. ets-5 may also autoregulate
      its expression in BAG neurons. ets-5 is not required for BAG neuron formation,
      indicating that it is specifically involved in BAG neuron differentiation and the
      maintenance of BAG neuron cell fate. Our results demonstrate a novel role for ETS
      genes in the development and function of gas-detecting sensory neurons.

PMID- 21954163
TI  - Quantifying the variation in the effective population size within a genome.
AB  - The effective population size (N(e)) is one of the most fundamental parameters in
      population genetics. It is thought to vary across the genome as a consequence of
      differences in the rate of recombination and the density of selected sites due to
      the processes of genetic hitchhiking and background selection. Although it is
      known that there is intragenomic variation in the effective population size in
      some species, it is not known whether this is widespread or how much variation in
      the effective population size there is. Here, we test whether the effective
      population size varies across the genome, between protein-coding genes, in 10
      eukaryotic species by considering whether there is significant variation in
      neutral diversity, taking into account differences in the mutation rate between
      loci by using the divergence between species. In most species we find significant
      evidence of variation. We investigate whether the variation in N(e) is correlated
      to recombination rate and the density of selected sites in four species, for
      which these data are available. We find that N(e) is positively correlated to
      recombination rate in one species, Drosophila melanogaster, and negatively
      correlated to a measure of the density of selected sites in two others, humans
      and Arabidopsis thaliana. However, much of the variation remains unexplained. We
      use a hierarchical Bayesian analysis to quantify the amount of variation in the
      effective population size and show that it is quite modest in all species-most
      genes have an N(e) that is within a few fold of all other genes. Nonetheless we
      show that this modest variation in N(e) is sufficient to cause significant
      differences in the efficiency of natural selection across the genome, by
      demonstrating that the ratio of the number of nonsynonymous to synonymous
      polymorphisms is significantly correlated to synonymous diversity and estimates
      of N(e), even taking into account the obvious nonindependence between these
      measures.

PMID- 21954164
TI  - Association between seed dormancy and pericarp color is controlled by a
      pleiotropic gene that regulates abscisic acid and flavonoid synthesis in weedy
      red rice.
AB  - Seed dormancy has been associated with red grain color in cereal crops for a
      century. The association was linked to qSD7-1/qPC7, a cluster of quantitative
      trait loci for seed dormancy/pericarp color in weedy red rice. This research
      delimited qSD7-1/qPC7 to the Os07g11020 or Rc locus encoding a basic helix-loop
      helix family transcription factor by intragenic recombinants and provided
      unambiguous evidence that the association arises from pleiotropy. The pleiotropic
      gene expressed in early developing seeds promoted expression of key genes for
      biosynthesis of abscisic acid (ABA), resulting in an increase in accumulation of
      the dormancy-inducing hormone; activated a conserved network of eight genes for
      flavonoid biosynthesis to produce the pigments in the lower epidermal cells of
      the pericarp tissue; and enhanced seed weight. Thus, the pleiotropic locus most
      likely controls the dormancy and pigment traits by regulating ABA and flavonoid
      biosynthetic pathways, respectively. The dormancy effect could be eliminated by a
      heat treatment, but could not be completely overcome by gibberellic acid or
      physical removal of the seed maternal tissues. The dormancy-enhancing alleles
      differentiated into two groups basically associated with tropical and temperate
      ecotypes of weedy rice. Of the pleiotropic effects, seed dormancy could
      contribute most to the weed adaptation. Pleiotropy prevents the use of the
      dormancy gene to improve resistance of white pericarp cultivars against pre
      harvest sprouting through conventional breeding approaches.

PMID- 21954165
TI  - Highly enantioselective intermolecular alkylation of aldehydes with alcohols by
      cooperative catalysis of diarylprolinol silyl ether with Bronsted acid.

PMID- 21954166
TI  - Relationship between accelerometer-based measures of physical activity and the
      Yale Physical Activity Survey in adults with arthritis.
AB  - OBJECTIVE: To evaluate the correlation between the Yale Physical Activity Survey
      (YPAS) scores and objective accelerometer measures of time spent in light
      intensity physical activities, moderate to vigorous intensity physical
      activities, and moderate to vigorous activities in bouts lasting at least 10
      minutes. METHODS: This study analyzed baseline data from 171 persons with
      rheumatoid arthritis (RA) and 139 persons with osteoarthritis (OA) in a
      randomized clinical trial (Increasing Motivation for Physical Activity in
      Arthritis Clinical Trial). Persons fulfilling the 1987 American College of
      Rheumatology criteria for RA and persons with symptomatic radiologic knee OA
      (Kellgren/Lawrence class >=2) wore an accelerometer for 7 days, then responded to
      the YPAS questionnaire and questions regarding demographics (age, sex, and race)
      and health factors (body mass index, disease status [Health Assessment
      Questionnaire/Western Ontario and McMaster Universities Osteoarthritis Index],
      comorbidities, pain, and function). Spearman's correlation coefficients were
      estimated between each YPAS summary measure and accelerometer measures. RESULTS:
      In the RA participants, the strongest correlation was between the YPAS activity
      dimensions summary index (Y-ADSI) and average daily minutes of bouted
      moderate/vigorous activity (r = 0.51). Additionally, the Y-ADSI correlated
      significantly with both objectively measured average daily accelerometer counts
      (r = 0.45) and average daily minutes of moderate/vigorous activity (r = 0.43).
      For OA participants, a similar pattern emerged: the Y-ADSI had significant
      correlations with average daily minutes of bouted moderate/vigorous activity (r =
      0.36), average daily minutes of moderate/vigorous activity (r = 0.31), and
      average daily counts (r = 0.24). CONCLUSION: For both the RA and OA groups, the Y
      ADSI had the strongest significant correlations with objectively measured
      physical activity, which supports Y-ADSI use as a tool for clinical applications
      and in rheumatology research.

PMID- 21954167
TI  - Separation of plutonium oxide nanoparticles and colloids.

PMID- 21954168
TI  - Left ventricular noncompaction and aneurysm revealed by left ventriculography.
AB  - Left ventriculography (LVG) is sometimes not performed during cardiac
      catheterization when results of prior noninvasive tests are available. We present
      a rare case of left ventricular noncompaction coexisting with left ventricular
      aneurysm diagnosed during cardiac catheterization. LVG could provide additional
      information in patients with nonobstructive coronary artery disease and decreased
      ejection fraction on noninvasive tests.

PMID- 21954169
TI  - Implementation of a continuous admission model reduces the length of stay of
      patients on an internal medicine clinical teaching unit.
AB  - BACKGROUND: Optimizing hospital operations is a critical issue facing healthcare
      systems. Reducing unnecessary variation in patient flow is likely to improve
      efficiency and optimize capacity for hospital inpatients. The objective of this
      study was to determine whether changing admissions, from a "bolus" system to a
      "drip" system, would result in a smoothed daily discharge rate, and reduce the
      length of stay of patients on a General Internal Medicine clinical teaching unit
      over a period of 1 year. METHODS: We conducted a retrospective analysis of the
      General Internal Medicine inpatient service at Toronto General Hospital for the 6
      month periods from March to August during 2 consecutive years. Length of stay
      distributions and daily discharge rate variations were compared between the 2
      study periods. RESULTS: There were a total of 2734 discharges, 1446 occurring in
      the pre-change period, and 1288 in the post-change period. There was overall
      smoothing of the daily discharge rates, and a reduction of 0.3 days in median
      length of stay in the post-change period (P = 0.0065). CONCLUSIONS: Restructuring
      the admission system to achieve constant daily admissions to each care team
      resulted in a smoothing of daily discharge rates and improved operational
      efficiency with shorter lengths of stay.

PMID- 21954170
TI  - Characterization and feasibility of a miniaturized stirred tank bioreactor to
      perform E. coli high cell density fed-batch fermentations.
AB  - The use of small scale bioreactors that are mechanically and functionally similar
      to large scale reactors is highly desirable to accelerate bioprocess development
      because they enable well-defined scale translations. In this study, a 25-mL
      miniaturized stirred tank bioreactor (MSBR) has been characterized in terms of
      its power input, hydrodynamics, and volumetric oxygen transfer coefficient
      (k(L)a) to assess its potential to grow high cell density (HCD) cultures using
      adequate scale-down criteria. Engineering characterization results show scale
      down, based on matched specific power input (P(G)/V), is feasible from a 20-L
      pilot scale stirred tank bioreactor. Results from fed-batch fermentations
      performed using Fab' producing E. coli W3110 at matched (P(G)/V) in the MSBR and
      20-L STR demonstrated that the MSBR can accurately scale down the 20-L
      fermentation performance in terms of growth and Fab' production. Successful
      implementation of a fed-batch strategy in the MSBR resulted in maximum optical
      density of ca. 114 and total Fab' concentration of 940 MUg/mL compared with ca.
      118 and 990 MUg/mL in 20-L STR. Furthermore, the use of the MSBR in conjunction
      with primary recovery scale-down tools to assess the harvest material of both
      reactors showed comparable shear sensitivity and centrifugation performance. The
      conjoint use of the MSBR with ultra scale-down (USD) centrifugation mimics can
      provide a cost-efficient manner in which to design and develop bioprocesses that
      account for good upstream performance as well as their manufacturability
      downstream.

PMID- 21954171
TI  - Nanocarriers for cytoplasmic delivery: cellular uptake and intracellular fate of
      chitosan and hyaluronic acid-coated chitosan nanoparticles in a phagocytic cell
      model.
AB  - The cellular uptake of hyaluronic-acid-coated, negatively charged
      chitosan/triphosphate nanoparticles and that of uncoated, positively charged ones
      is investigated by studying cellular localization, uptake kinetics and mechanism
      of internalization in J774.2 macrophages, using non-phagocytic L929 fibroblasts
      as a control for uncoated nanoparticles. Both kinds of nanoparticles undergo
      endosomal escape and adopt a similar clathrin-based endocytic mechanism. The
      surface decoration with HA profoundly influences the kinetics of cellular uptake,
      with an at least two orders of magnitude slower kinetics, but also the nature of
      the binding on the cellular surface.

PMID- 21954172
TI  - Rapid prescreening in gynecologic cytology: A more efficient quality assurance
      method.

PMID- 21954173
TI  - Primary lymphedema with coarctation of the aorta: possible new syndrome or
      variant of Irons-Bianchi syndrome?
AB  - We present a boy with congenital lymphedema, a congenital heart defect
      (coarctation of the aorta), and mild dysmorphic features. Clinical impression and
      targeted investigations ruled out Noonan syndrome and Milroy syndrome, but it was
      not clear whether or not he had Irons-Bianchi syndrome. We discuss the genomic
      and lymphoscintigraphy evaluation of this case, and review whether the small
      number of current case reports represent the original Irons-Bianchi syndrome or
      variants. We anticipate that ongoing molecular investigations such as Next
      Generation Sequencing will delineate a currently clinically defined phenotypic
      spectrum.

PMID- 21954174
TI  - Hyperthermia induces upregulation of connexin43 in the golden hamster neural
      tube.
AB  - BACKGROUND: During early embryonic development, maternal exposure to hyperthermia
      induces neural tube defects (NTDs). Connexins are essential for the formation of
      gap junctions and Connexin43 (Cx43) is crucially involved in neural tube
      development. This study was designed to explore the potential role of Cx43 in
      NTDs induced by hyperthermia. METHODS: Using PCR, the Cx43 cDNA was screened from
      the cDNA library of the neural tube from golden hamsters treated with
      hyperthermia. By Northern blot, the expression of Cx43 in heat-treated and
      control groups of the golden hamsters at day 8.5 after mating was detected.
      Finally, by in situ hybridization and RT-PCR, the expression of Cx43 was examined
      in the neural tube at different time points after heat treatment. RESULTS: Cx43
      was stably expressed in heat-treated and control groups of the golden hamsters,
      whereas the expression was evidently higher in the heat-treated group. Cx43
      expression in the neural tube at different time points after heat treatment was
      significantly higher than in control groups (p < 0.01). Hyperthermia did not
      induce any mutations in Cx43 cDNA. CONCLUSIONS: Our data provide the first
      evidence that hyperthermia induces upregulation of Cx43 in the golden hamster
      neural tube. NTDs caused by hyperthermia may be intimately related with the
      overexpression of Cx43.

PMID- 21954175
TI  - Vibralactone as a tool to study the activity and structure of the ClpP1P2 complex
      from Listeria monocytogenes.

PMID- 21954176
TI  - Robot-assisted partial and total splenectomy.
AB  - BACKGROUND: The interest of robotics in performing partial and total splenectomy
      is poorly reported so far. We report herein our experience. METHODS: From
      November 2001 to November 2009, 24 consecutive robotic splenectomies were
      performed by the same surgeon. All data were prospectively collected and reviewed
      retrospectively. RESULTS: Twelve men and 12 women with a median age of 48 years
      underwent a robotic splenectomy, three of which were partial splenectomies. The
      indications were: ABO incompatibility for kidney transplantation (n = 7),
      haematological disease (n = 7) and miscellaneous pathologies (n = 10). Mean
      operative time was 199 +/- 65 min. Median blood loss was 75 (range 5-300) ml.
      There was one intraoperative complication and two conversions. The postoperative
      morbidity was 8.3% with no mortality. Median hospital stay was 5.5 days.
      CONCLUSIONS: This series reports the safety and feasibility of robotic partial
      and total splenectomy. Its use as an alternative to the standard laparoscopic
      approach is particularly beneficial in more challenging cases.

PMID- 21954177
TI  - Raman spectroscopy for the non-contact and non-destructive monitoring of collagen
      damage within tissues.
AB  - The non-destructive and label-free monitoring of extracellular matrix (ECM)
      remodeling and degradation processes is a great challenge. Raman spectroscopy is
      a non-contact method that offers the possibility to analyze ECM in situ without
      the need for tissue processing. Here, we employed Raman spectroscopy for the
      detection of heart valve ECM, focusing on collagen fibers. We screened the
      leaflets of porcine aortic valves either directly after dissection or after
      treatment with collagenase. By comparing the fingerprint region of the Raman
      spectra of control and treated tissues (400-1800 cm(-1)), we detected no
      significant differences based on Raman shifts; however, we found that increasing
      collagen degradation translated into decreasing Raman signal intensities. After
      these proof-of-principal experiments, we compared Raman spectra of native and
      cryopreserved valve tissues and revealed that the signal intensities of the
      frozen samples were significantly lower compared to those of native tissues,
      similar to the data seen in the enzymatically-degraded tissues. In conclusion,
      our data demonstrate that Raman microscopy is a promising, non-destructive and
      non-contact tool to probe ECM state in situ.

PMID- 21954179
TI  - Diagnostic accuracy of range of motion measurements in early symptomatic hip
      and/or knee osteoarthritis.
AB  - OBJECTIVE: To examine the diagnostic accuracy of hip internal rotation, hip
      flexion, and knee flexion measurements for the presence of osteophytosis and
      joint space narrowing (JSN) in early symptomatic osteoarthritis (OA). METHODS:
      The baseline data for 598 participants of the Cohort Hip & Cohort Knee study were
      used. Participants underwent a standardized physical and radiographic
      examination. The active range of motion (ROM) was assessed using a goniometer.
      The ROM cutoff with the highest discriminative ability for radiographic features
      of OA was defined by maximizing the sum of the sensitivity and specificity.
      Several diagnostic measures were calculated to establish the diagnostic accuracy
      of ROM measurements for the presence of radiographic features. RESULTS: In
      patients with hip symptoms, hip internal rotation <24 degrees  and flexion <114
      degrees  were found to be the cutoffs with the highest discriminative ability to
      distinguish between patients with and without radiographic features. In patients
      with knee symptoms, knee flexion <132 degrees  was the cutoff with the highest
      discriminative ability. The American College of Rheumatology (ACR) criterion of
      hip internal rotation <15 degrees  increased the probability of the presence of
      osteophytosis or JSN from 25% to 58%. The diagnostic accuracy of hip and knee
      flexion measurements was low. CONCLUSION: To reduce the number of patients that
      are not identified by the ACR criterion of hip internal rotation <15 degrees , it
      is recommended to change the cutoff to internal rotation <24 degrees  in patients
      with early symptomatic OA. Individual hip and knee flexion measurements seem to
      be of little diagnostic value in early symptomatic OA.

PMID- 21954180
TI  - Catalytic redox reactions in the CO/N2O system mediated by the bimetallic oxide
      cluster couple AlVO3+/AlVO4+.

PMID- 21954178
TI  - Yeast Nrd1, Nab3, and Sen1 transcriptome-wide binding maps suggest multiple roles
      in post-transcriptional RNA processing.
AB  - RNA polymerase II transcribes both coding and noncoding genes, and termination of
      these different classes of transcripts is facilitated by different sets of
      termination factors. Pre-mRNAs are terminated through a process that is coupled
      to the cleavage/polyadenylation machinery, and noncoding RNAs in the yeast
      Saccharomyces cerevisiae are terminated through a pathway directed by the RNA
      binding proteins Nrd1, Nab3, and the RNA helicase Sen1. We have used an in vivo
      cross-linking approach to map the binding sites of components of the yeast non
      poly(A) termination pathway. We show here that Nrd1, Nab3, and Sen1 bind to a
      number of noncoding RNAs in an unexpected manner. Sen1 shows a preference for
      H/ACA over box C/D snoRNAs. Nrd1, which binds to snoRNA terminators, also binds
      to the upstream region of some snoRNA transcripts and to snoRNAs embedded in
      introns. We present results showing that several RNAs, including the telomerase
      RNA TLC1, require Nrd1 for proper processing. Binding of Nrd1 to transcripts from
      tRNA genes is another unexpected observation. We also observe RNA polymerase II
      binding to transcripts from RNA polymerase III genes, indicating a possible role
      for the Nrd1 pathway in surveillance of transcripts synthesized by the wrong
      polymerase. The binding targets of Nrd1 pathway components change in the absence
      of glucose, with Nrd1 and Nab3 showing a preference for binding to sites in the
      mature snoRNA and tRNAs. This suggests a novel role for Nrd1 and Nab3 in
      destruction of ncRNAs in response to nutrient limitation.

PMID- 21954181
TI  - Three-dimensional imaging of fibrous cap by frequency-domain optical coherence
      tomography.
AB  - Histopathological data correlated the presence of thin-cap fibroatheroma (TCFA)
      with adverse cardiovascular events. Intravascular optical coherence tomography
      (iOCT) is currently the only imaging modality with sufficiently high axial
      resolution (~15 MUm) that allows direct fibrous-cap (FC) assessment in vivo. iOCT
      quantification of TCFA has been validated, but the assessment of a single cross
      sectional image does not depict the complexity of the atherosclerotic plaque. We
      present two cases that illustrate the importance of three-dimensional volumetric
      quantification of the FC capitalizing on the properties of frequency-domain iOCT.

PMID- 21954182
TI  - pH-stat fed-batch process to enhance the production of cis, cis-muconate from
      benzoate by Pseudomonas putida KT2440-JD1.
AB  - Pseudomonas putida KT2440-JD1 is able to cometabolize benzoate to cis, cis
      muconate in the presence of glucose as growth substrate. P. putida KT2440-JD1 was
      unable to grow in the presence of concentrations above 50 mM benzoate or 600 mM
      cis, cis-muconate. The inhibitory effects of both compounds were cumulative. The
      maximum specific uptake rate of benzoate was higher than the specific production
      rate of cis, cis-muconate during growth on glucose in the presence of benzoate,
      indicating that a benzoate derivative accumulated in the cells, which is likely
      to be catechol. Catechol was shown to reduce the expression level of the ben
      operon, which encodes the conversion of benzoate to cis, cis-muconate. To prevent
      overdoses of benzoate, a pH-stat fed-batch process for the production of cis, cis
      muconate from benzoate was developed, in which the addition of benzoate was
      coupled to the acidification of the medium. The maximum specific production rate
      during the pH-stat fed-batch process was 0.6 g (4.3 mmol) g dry cell weight(-1)
      h(-1), whereas 18.5 g L(-1) cis, cis-muconate accumulated in the culture medium
      with a molar product yield of close to 100%. Proteome analysis revealed that the
      outer membrane protein H1 was upregulated during the pH-stat fed-batch process,
      whereas the expression of 10 other proteins was reduced. The identified proteins
      are involved in energy household, transport, translation of RNA, and motility.

PMID- 21954185
TI  - Lipids as effectors. Editorial.

PMID- 21954183
TI  - Bilayer matrix composed of polycation/DNA complex and sodium alginate gel as a
      tumor cell catcher.
AB  - A bilayer matrix consisting of TABP-SS/DNA complexes and sodium alginate gel is
      formed via electrostatic interaction. In vitro cell adhesion, proliferation and
      transfection of the bilayer matrix are investigated in HepG2, HeLa and COS7
      cells. Results show that this matrix can only promote tumor cell attachment and
      growth. Compared with normal cells, the bilayer matrix exhibits significantly
      higher transfection efficacy in tumor cells. Cell co-culture competitive
      transfection assay shows that the cell uptake of TABP-SS/DNA complexes is
      significantly enhanced in tumor cells rather than normal cells under the co
      culture competitive condition, which confirms that TABP-SS/DNA complexes have
      strong tumor cell selectivity and tumor targeting transfection ability.

PMID- 21954186
TI  - Dietary lipids and their oxidized products in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the commonest form of dementia in the elderly,
      characterized by memory dysfunction, loss of lexical access, spatial and temporal
      disorientation, and impaired judgment. A growing body of scientific literature
      addresses the implication of dietary habits in the pathogenesis of AD. This
      review reports recent findings concerning the modulation of AD development by
      dietary lipids, in animals and humans, focusing on the pathogenetic role of lipid
      oxidation products. Oxidative breakdown products of omega-6 polyunsaturated fatty
      acids (omega-6 PUFAs), and cholesterol oxidation products (oxysterols), might
      play a role in favoring beta-amyloid deposition, a hallmark of AD's onset and
      progression. Conversely, omega-3 PUFAs appear to contribute to preventing and
      treating AD. However, high concentrations of omega-3 PUFAs can also produce
      oxidized derivatives reacting with important functions of nervous cells. Thus,
      altered balances between cholesterol and oxysterols, and between omega-3 and
      omega-6 PUFAs must be considered in AD's pathophysiology. The use of a diet with
      an appropriate omega-3/omega-6 PUFA ratio, rich in healthy oils, fish and
      antioxidants, such as flavonoids, but low in cholesterol-containing foods, can be
      a beneficial component in the clinical strategies of prevention of AD.

PMID- 21954187
TI  - Ginger phytochemicals mitigate the obesogenic effects of a high-fat diet in mice:
      a proteomic and biomarker network analysis.
AB  - SCOPE: Natural dietary anti-obesogenic phytochemicals may help combat the rising
      global incidence of obesity. We aimed to identify key hepatic pathways targeted
      by anti-obsogenic ginger phytochemicals fed to mice. METHODS AND RESULTS: Weaning
      mice were fed a high-fat diet containing 6-gingerol (HFG), zerumbone (HFZ), a
      characterized rhizome extract of the ginger-related plant Alpinia officinarum
      Hance (high fat goryankang, HFGK) or no phytochemicals (high-fat control, HFC)
      for 6 wks and were compared with mice on a low-fat control diet (LFC). Increased
      adiposity in the HFC group, compared with the LFC group, was significantly
      (p<0.05) reduced in the HFG and HFGK groups without food intake being affected.
      Correlation network analysis, including a novel residuals analysis, was utilized
      to investigate relationships between liver proteomic data, lipid and cholesterol
      biomarkers and physiological indicators of adiposity. 6-Gingerol significantly
      increased plasma cholesterol but hepatic farnesyl diphosphate synthetase, which
      is involved in cholesterol biosynthesis was decreased, possibly by negative
      feedback. Acetyl-coenzyme A acyltransferase 1 and enoyl CoA hydratase, which
      participate in the beta-oxidation of fatty acids were significantly (p<0.05)
      increased by consumption of phytochemical-supplemented diets. CONCLUSION: Dietary
      ginger phytochemicals target cholesterol metabolism and fatty acid oxidation in
      mice, with anti-obesogenic but also hypercholesterolemic consequences.

PMID- 21954188
TI  - Conjugated linoleic acid protects against gliadin-induced depletion of intestinal
      defenses.
AB  - SCOPE: The involvement of oxidative stress in gluten-induced toxicity has been
      evidenced in vitro and in clinical studies but has never been examined in vivo.
      We recently demonstrated the protective activity of conjugated linoleic acid
      (CLA), which functions by the activation of nuclear factor erythroid 2-related
      factor2 (Nrf2), a key transcription factor for the synthesis of antioxidant and
      detoxifying enzymes (phase 2). Here, we evaluate the involvement of nuclear
      factor erythroid 2-related factor2 in gliadin-mediated toxicity in human Caco-2
      intestinal cells and in gliadin-sensitive human leukocyte antigen-DQ8 transgenic
      mice (DQ8) and the protective activity of CLA. METHODS AND RESULTS: Gliadin
      effects in differentiated Caco-2 cells and in DQ8 mice, fed with a gliadin
      containing diet with or without CLA supplementation, were evaluated by combining
      enzymatic, immunochemical, immunohistochemical, and quantitative real-time PCR
      (qRT-PCR) assays. Gliadin toxicity was accompanied by downregulation of phase 2
      and elevates proteasome-acylpeptide hydrolase activities in vitro and in vivo.
      Notably, gliadin was unable to generate severe oxidative stress extent or
      pathological consequences in DQ8 mice intestine comparable to those found in
      celiac patients and the alterations produced were hampered by CLA. CONCLUSION:
      The beneficial effects of CLA against the depletion of crucial intestinal
      cytoprotective defenses indicates a novel nutritional approach for the treatment
      of intestinal disease associated with altered redox homeostasis.

PMID- 21954189
TI  - High throughput flow cytometry based yeast two-hybrid array approach for large
      scale analysis of protein-protein interactions.
AB  - The analysis of protein-protein interactions is a key focus of proteomics
      efforts. The yeast two-hybrid system (Y2H) has been the most commonly used method
      in genome-wide searches for protein interaction partners. However, the throughput
      of the current yeast two-hybrid array approach is hampered by the involvement of
      the time-consuming LacZ assay and/or the incompatibility of liquid handling
      automation due to the requirement for selection of colonies/diploids on agar
      plates. To facilitate large-scale Y2H assays, we report a novel array approach by
      coupling a GFP reporter based Y2H system with high throughput flow cytometry that
      enables the processing of a 96-well plate in as little as 3 min. In this
      approach, the yEGFP reporter has been established in both AH109 (MATa) and Y187
      (MATalpha) reporter cells. It not only allows the generation of two copies of GFP
      reporter genes in diploid cells, but also allows the convenient determination of
      self-activators generated from both bait and prey constructs by flow cytometry.
      We demonstrate a Y2H array assay procedure that is carried out completely in
      liquid media in 96-well plates by mating bait and prey cells in liquid YPD media,
      selecting the diploids containing positive interaction pairs in selective media
      and analyzing the GFP reporter directly by flow cytometry. We have evaluated this
      flow cytometry based array procedure by showing that the interaction of the
      positive control pair P53/T is able to be reproducibly detected at 72 hr
      postmating compared with the negative control pairs. We conclude that our flow
      cytometry based yeast two-hybrid approach is robust, convenient, quantitative,
      and is amenable to large-scale analysis using liquid-handling automation.

PMID- 21954190
TI  - Simultaneous photographing of oxygen and pH in vivo using sensor films.

PMID- 21954191
TI  - Improvement in the routine screening of cervical smears: A study using rapid
      prescreening and 100% rapid review as internal quality control methods.
AB  - BACKGROUND: High rates of false-negative results constitute a routine problem in
      cytology laboratories. Of currently available internal quality control methods,
      10% random review is the least effective in detecting false-negatives in routine
      screening. There is evidence that 100% rapid review and rapid prescreening
      perform well for this purpose. This study compared the performance of rapid
      prescreening and 100% rapid review as internal quality control methods for
      cervical cytology exams. METHODS: Over 27 months, 12,208 cervical cytology smears
      were submitted to rapid prescreening and routine screening. The 100% rapid review
      method was performed on all smears classified as negative or unsatisfactory at
      routine screening. Conflicting results obtained with either method were reviewed
      in detail to define final diagnosis, which was considered the gold standard for
      evaluating the performance of rapid prescreening and 100% rapid review. RESULTS:
      Compared with final diagnosis, the sensitivity of routine screening and rapid
      prescreening was 72.9% and 75.6%, respectively. Considering only smears
      classified as negative or unsatisfactory at routine screening, the sensitivity of
      rapid prescreening and 100% rapid review was 90.2% and 57,0%, respectively. Of
      244 cases (2.0%) of false-negative results at routine screening, rapid
      prescreening identified 220 cases (1.80%), whereas 100% rapid review identified
      140 (1.15%). Rapid prescreening detected all cases of HSIL identified as false
      negatives. CONCLUSIONS: Rapid prescreening is more effective than 100% rapid
      review for the detection of false-negatives at routine screening, thus providing
      subsidies for the performance of cervical cytology, the principal function of
      which is to detect precursor lesions of cervical cancer.

PMID- 21954192
TI  - Maternal occupational pesticide exposure and risk of hypospadias in the National
      Birth Defects Prevention Study.
AB  - BACKGROUND: Hypospadias is a common congenital malformation among men in which
      the urethral opening is ventrally displaced. Pesticide exposure has been
      suggested as a possible etiologic factor, but previous epidemiologic studies have
      produced inconsistent results. METHODS: We used data from the National Birth
      Defects Prevention Study (NBDPS), a population-based case-control study, to
      examine maternal occupational exposure to fungicides, insecticides, and
      herbicides among 647 hypospadias case infants and 1496 unaffected male control
      infants with estimated delivery dates from October 1997 to December 2002.
      Periconceptional (1 month before conception through the first trimester of
      pregnancy) pesticide exposures were assigned by an expert rater, assisted by a
      job-exposure matrix (JEM), from a job history completed by mothers during a
      telephone interview. Odds ratios (ORs) and 95% confidence intervals (CIs) were
      calculated with multivariable logistic regression, and adjusted for relevant
      covariates. RESULTS: Maternal periconceptional occupational exposure to any
      pesticides (yes/no) was not associated with an increased risk of hypospadias (OR
      = 0.78; 95% CI = 0.61-1.01). Maternal occupational periconceptional pesticide
      exposure type (insecticides, fungicides, and herbicides) and estimated quantity
      also showed no significantly increased risk of hypospadias and no evidence of a
      dose-response relationship; however, the estimated pesticide exposure levels in
      this population were low. CONCLUSION: Using broad classes of insecticides,
      herbicides, and fungicides, we found no evidence that low intensity maternal
      periconceptional occupational pesticide exposure was a risk factor for
      hypospadias.

PMID- 21954193
TI  - Exogenous application of salicylic acid to alleviate the toxic effects of
      insecticides in Vicia faba L.
AB  - The present study investigated the possible mediatory role of salicylic acid (SA)
      in protecting plants from insecticides toxicity. The seeds of Vicia faba var IIVR
      Selection-1 were treated with different concentrations (1.5, 3.0, and 6.0 ppm) of
      the insecticides alphamethrin (AM) and endosulfan (ES) for 6 h with and without
      12 h conditioning treatment of SA (0.01 mM). Insecticides treatment caused a
      significant decrease in mitotic index (MI) and induction of different types of
      chromosomal abnormalities in the meristematic cells of broad bean roots.
      Pretreatment of seeds with SA resulted in increased MI and significant reduction
      of chromosomal abnormalities. SA application also regulated proline accumulation
      and carotenoid content in the leaf tissues. SA resulted in the decrement of
      insecticides induced increase in proline content and increased the carotenoids
      content. These results illustrate the ameliorating effect of SA under stress
      conditions and reveal that SA is more effective in alleviating the toxic effects
      of insecticides at higher concentrations than that at lower concentrations.

PMID- 21954194
TI  - SVM-based validation of motor unit potential trains extracted by EMG signal
      decomposition.
AB  - Motor unit potential trains (MUPTs) extracted via electromyographic (EMG) signal
      decomposition can aid in the diagnosis of neuromuscular disorders and the study
      of the neural control of movement, but only if they are valid. In this paper,
      support vector machine (SVM)-based supervised classifiers are proposed to
      estimate the validity of extracted MUPTs. The classifiers use either the MU
      firing pattern or the MUP shape consistency of an MUPT, or both, to estimate its
      validity. The developed classifiers estimate the class label of an MUPT (i.e.,
      valid/invalid) and a degree of support for the decision being made. A single SVM
      that estimates the validity of a given MUPT using extracted MU firing pattern and
      MUP shape features was investigated. In addition, the effectiveness of
      multiclassifier techniques which estimate the overall validity of a train by
      fusing the MU firing pattern and MUP shape validity of a given MUPT, determined
      separately by two distinct SVMs, was also investigated. Training based only on
      simulated data showed robust classification performance of the several
      multiclassifier methods when tested using both simulated and real test data. Of
      the methods studied, the multiclassifier constructed using trainable logistic
      regression to aggregate base classifier outputs had the best performance.
      Assuming 12.7% of extracted MUPTs are on average invalid, the estimated accuracy
      for this method in correctly categorizing MUPTs extracted during decomposition
      was 99.4% and 98.8% for simulated and real data, respectively.

PMID- 21954195
TI  - Fascicle-selectivity of an intraneural stimulation electrode in the rabbit
      sciatic nerve.
AB  - The current literature contains extensive research on peripheral nerve
      interfaces, including both extraneural and intrafascicular electrodes.
      Interfascicular electrodes, which are in-between these two with respect to nerve
      fiber proximity have, however, received little interest. In this proof-of-concept
      study, an interfascicular electrode was designed to be implanted in the sciatic
      nerve and activate the tibial and peroneal nerves selectively of each other, and
      it was tested in acute experiments on nine anaesthetized rabbits. The electrode
      was inserted without difficulty between the fascicles using blunt glass tools,
      which could easily penetrate the epineurium but not the perineurium. Selective
      activation of all tibial and peroneal nerves in the nine animals was achieved
      with high selectivity (S = 0.98 +/- 0.02). Interfascicular electrodes could
      provide an interesting addition to the bulk of peripheral nerve interfaces
      available for neural prosthetic devices. Since interfascicular electrodes can be
      inserted without fully freeing the nerve and have the advantage of not confining
      the nerve to a limited space, they could, e.g., be an alternative to extraneural
      electrodes in locations where such surgery is complicated due to blood vessels or
      fatty tissue. Further studies are, however, necessary to develop biocompatible
      electrodes and test their stability and safety in chronic experiments.

PMID- 21954196
TI  - Tip of the tongue selectivity and motor learning in the palatal area.
AB  - This study assessed the ability of the tongue tip to accurately select intraoral
      targets embedded in an upper palatal tongue-computer interface, using 18 able
      bodied volunteers. Four performance measures, based on modifications to Fitts's
      Law, were determined for three different tongue-computer interface layouts. The
      layouts differed with respect to number and location of the targets in the
      palatal interface. Assessment of intraoral target selection speed and accuracy
      revealed that performance was indeed dependent on the location and distance
      between the targets. Performances were faster and more accurate for targets
      located farther away from the base of the tongue in comparison to posterior and
      medial targets. A regression model was built, which predicted intraoral target
      selection time based on target location and movement amplitude better than the
      predicted by using a standard Fitts's Law model. A 30% improvement in the speed
      and accuracy over three daily practice sessions of 30 min emphasizes the
      remarkable motor learning abilities of the tongue musculature and provides
      further evidence that the tongue is useful for operating computer-interface
      technologies.

PMID- 21954197
TI  - Effect of mesoporous TiO2 bead diameter in working electrodes on the efficiency
      of dye-sensitized solar cells.
AB  - Mesoporous TiO2 beads with diameters of 320+/-50, 550+/-50, and 830+/-40 nm,
      comprising interconnected and densely packed TiO2 nanocrystals, were used as
      working electrodes for dye-sensitized solar cells (DSCs). These electrodes
      possess high surface areas and superior light-scattering properties, which are
      ideal for DSC applications. Although the electrode prepared by using 320+/-50 nm
      beads demonstrated the highest dye loading and the electrode prepared by using
      550+/-50 nm beads showed the best light-scattering properties in the wavelength
      region lambda=400-800 nm, DSC devices with working electrodes composed of 830+/
      40 nm beads achieved the highest power conversion efficiencies of 9.0 % after
      treatment with TiCl4. A higher electron diffusion rate (4.35*10-4 cm2  s-1) and
      an extended electron lifetime (58 ms) were observed in DSCs composed of the
      largest beads, 830+/-40 nm, attributable to a reduced amount of inter-bead
      barriers and a relatively small percentage of TiO2 nanocrystals on the surface of
      the beads, compared to cells containing 550+/-50 and 320+/-50 nm beads.

PMID- 21954198
TI  - Impact of educational and patient decision aids on decisional conflict associated
      with total knee arthroplasty.
AB  - OBJECTIVE: To examine the impact of a videobooklet patient decision aid
      supplemented by an interactive values clarification exercise on decisional
      conflict in patients with knee osteoarthritis (OA) considering total knee
      arthroplasty. METHODS: A total of 208 patients participated in the study (mean
      age 63 years, 68% female, and 66% white). Participants were randomized to 1 of 3
      groups: 1) educational booklet on OA management (control), 2) patient decision
      aid (videobooklet) on OA management, and 3) patient decision aid (videobooklet) +
      adaptive conjoint analysis (ACA) tool. The ACA tool enables patients to consider
      competing attributes (i.e., specific risks/benefits) by asking them to rate a
      series of paired comparisons. The primary outcome was the decisional conflict
      scale ranging from 0-100. Differences between groups were analyzed using analysis
      of variance and Tukey's honestly significant difference tests. RESULTS: Overall,
      decisional conflict decreased significantly in all groups (P < 0.05). The largest
      reduction in decisional conflict was observed for participants in the
      videobooklet decision aid group (21 points). Statistically significant
      differences in pre- versus postintervention total scores favored the videobooklet
      group compared to the control group (21 versus 10) and to the videobooklet plus
      ACA group (21 versus 14; P < 0.001). Changes in the decisional conflict score for
      the control group compared to the videobooklet decision aid + ACA group were not
      significantly different. CONCLUSION: In our study, an audiovisual patient
      decision aid decreased decisional conflict more than printed material alone or
      the addition of a more complex computer-based ACA tool requiring more intense
      cognitive involvement and explicit value choices.

PMID- 21954199
TI  - A semi-Markov model for mitosis segmentation in time-lapse phase contrast
      microscopy image sequences of stem cell populations.
AB  - We propose a semi-Markov model trained in a max-margin learning framework for
      mitosis event segmentation in large-scale time-lapse phase contrast microscopy
      image sequences of stem cell populations. Our method consists of three steps.
      First, we apply a constrained optimization based microscopy image segmentation
      method that exploits phase contrast optics to extract candidate subsequences in
      the input image sequence that contains mitosis events. Then, we apply a max
      margin hidden conditional random field (MM-HCRF) classifier learned from human
      annotated mitotic and nonmitotic sequences to classify each candidate subsequence
      as a mitosis or not. Finally, a max-margin semi-Markov model (MM-SMM) trained on
      manually-segmented mitotic sequences is utilized to reinforce the mitosis
      classification results, and to further segment each mitosis into four predefined
      temporal stages. The proposed method outperforms the event-detection CRF model
      recently reported by Huh as well as several other competing methods in very
      challenging image sequences of multipolar-shaped C3H10T1/2 mesenchymal stem
      cells. For mitosis detection, an overall precision of 95.8% and a recall of 88.1%
      were achieved. For mitosis segmentation, the mean and standard deviation for the
      localization errors of the start and end points of all mitosis stages were well
      below 1 and 2 frames, respectively. In particular, an overall temporal location
      error of 0.73 +/- 1.29 frames was achieved for locating daughter cell birth
      events.

PMID- 21954201
TI  - Relationships between patients, informal caregivers and health professionals in
      care homes.

PMID- 21954202
TI  - Provision of essential newborn care training to midwives in Zambia is a low-cost
      intervention that reduces neonatal mortality.

PMID- 21954200
TI  - Medusa: a scalable MR console using USB.
AB  - Magnetic resonance imaging (MRI) pulse sequence consoles typically employ closed
      proprietary hardware, software, and interfaces, making difficult any adaptation
      for innovative experimental technology. Yet MRI systems research is trending to
      higher channel count receivers, transmitters, gradient/shims, and unique
      interfaces for interventional applications. Customized console designs are now
      feasible for researchers with modern electronic components, but high data rates,
      synchronization, scalability, and cost present important challenges. Implementing
      large multichannel MR systems with efficiency and flexibility requires a scalable
      modular architecture. With Medusa, we propose an open system architecture using
      the universal serial bus (USB) for scalability, combined with distributed
      processing and buffering to address the high data rates and strict
      synchronization required by multichannel MRI. Medusa uses a modular design
      concept based on digital synthesizer, receiver, and gradient blocks, in
      conjunction with fast programmable logic for sampling and synchronization. Medusa
      is a form of synthetic instrument, being reconfigurable for a variety of
      medical/scientific instrumentation needs. The Medusa distributed architecture,
      scalability, and data bandwidth limits are presented, and its flexibility is
      demonstrated in a variety of novel MRI applications.

PMID- 21954203
TI  - Approximate dynamic programming for optimal stationary control with control
      dependent noise.
AB  - This brief studies the stochastic optimal control problem via reinforcement
      learning and approximate/adaptive dynamic programming (ADP). A policy iteration
      algorithm is derived in the presence of both additive and multiplicative noise
      using Ito calculus. The expectation of the approximated cost matrix is guaranteed
      to converge to the solution of some algebraic Riccati equation that gives rise to
      the optimal cost value. Moreover, the covariance of the approximated cost matrix
      can be reduced by increasing the length of time interval between two consecutive
      iterations. Finally, a numerical example is given to illustrate the efficiency of
      the proposed ADP methodology.

PMID- 21954204
TI  - Estimating the ultimate bound and positively invariant set for a class of
      Hopfield networks.
AB  - In this paper, we investigate the ultimate bound and positively invariant set for
      a class of Hopfield neural networks (HNNs) based on the Lyapunov stability
      criterion and Lagrange multiplier method. It is shown that a hyperelliptic
      estimate of the ultimate bound and positively invariant set for the HNNs can be
      calculated by solving a linear matrix inequality (LMI). Furthermore, the global
      stability of the unique equilibrium and the instability region of the HNNs are
      analyzed, respectively. Finally, the most accurate estimate of the ultimate bound
      and positively invariant set can be derived by solving the corresponding
      optimization problems involving the LMI constraints. Some numerical examples are
      given to illustrate the effectiveness of the proposed results.

PMID- 21954205
TI  - Asynchronous event-based hebbian epipolar geometry.
AB  - Epipolar geometry, the cornerstone of perspective stereo vision, has been studied
      extensively since the advent of computer vision. Establishing such a geometric
      constraint is of primary importance, as it allows the recovery of the 3-D
      structure of scenes. Estimating the epipolar constraints of nonperspective stereo
      is difficult, they can no longer be defined because of the complexity of the
      sensor geometry. This paper will show that these limitations are, to some extent,
      a consequence of the static image frames commonly used in vision. The
      conventional frame-based approach suffers from a lack of the dynamics present in
      natural scenes. We introduce the use of neuromorphic event-based--rather than
      frame-based--vision sensors for perspective stereo vision. This type of sensor
      uses the dimension of time as the main conveyor of information. In this paper, we
      present a model for asynchronous event-based vision, which is then used to derive
      a general new concept of epipolar geometry linked to the temporal activation of
      pixels. Practical experiments demonstrate the validity of the approach, solving
      the problem of estimating the fundamental matrix applied, in a first stage, to
      classic perspective vision and then to more general cameras. Furthermore, this
      paper shows that the properties of event-based vision sensors allow the
      exploration of not-yet-defined geometric relationships, finally, we provide a
      definition of general epipolar geometry deployable to almost any visual sensor.

PMID- 21954206
TI  - Learning speaker-specific characteristics with a deep neural architecture.
AB  - Speech signals convey various yet mixed information ranging from linguistic to
      speaker-specific information. However, most of acoustic representations
      characterize all different kinds of information as whole, which could hinder
      either a speech or a speaker recognition (SR) system from producing a better
      performance. In this paper, we propose a novel deep neural architecture (DNA)
      especially for learning speaker-specific characteristics from mel-frequency
      cepstral coefficients, an acoustic representation commonly used in both speech
      recognition and SR, which results in a speaker-specific overcomplete
      representation. In order to learn intrinsic speaker-specific characteristics, we
      come up with an objective function consisting of contrastive losses in terms of
      speaker similarity/dissimilarity and data reconstruction losses used as
      regularization to normalize the interference of non-speaker-related information.
      Moreover, we employ a hybrid learning strategy for learning parameters of the
      deep neural networks: i.e., local yet greedy layerwise unsupervised pretraining
      for initialization and global supervised learning for the ultimate discriminative
      goal. With four Linguistic Data Consortium (LDC) benchmarks and two non-English
      corpora, we demonstrate that our overcomplete representation is robust in
      characterizing various speakers, no matter whether their utterances have been
      used in training our DNA, and highly insensitive to text and languages spoken.
      Extensive comparative studies suggest that our approach yields favorite results
      in speaker verification and segmentation. Finally, we discuss several issues
      concerning our proposed approach.

PMID- 21954207
TI  - Design of a data-driven predictive controller for start-up process of AMT
      vehicles.
AB  - In this paper, a data-driven predictive controller is designed for the start-up
      process of vehicles with automated manual transmissions (AMTs). It is obtained
      directly from the input-output data of a driveline simulation model constructed
      by the commercial software AMESim. In order to obtain offset-free control for the
      reference input, the predictor equation is gained with incremental inputs and
      outputs. Because of the physical characteristics, the input and output
      constraints are considered explicitly in the problem formulation. The
      contradictory requirements of less friction losses and less driveline shock are
      included in the objective function. The designed controller is tested under
      nominal conditions and changed conditions. The simulation results show that,
      during the start-up process, the AMT clutch with the proposed controller works
      very well, and the process meets the control objectives: fast clutch lockup time,
      small friction losses, and the preservation of driver comfort, i.e., smooth
      acceleration of the vehicle. At the same time, the closed-loop system has the
      ability to reject uncertainties, such as the vehicle mass and road grade.

PMID- 21954208
TI  - Data-based hybrid tension estimation and fault diagnosis of cold rolling
      continuous annealing processes.
AB  - The continuous annealing process line (CAPL) of cold rolling is an important unit
      to improve the mechanical properties of steel strips in steel making. In
      continuous annealing processes, strip tension is an important factor, which
      indicates whether the line operates steadily. Abnormal tension profile
      distribution along the production line can lead to strip break and roll slippage.
      Therefore, it is essential to estimate the whole tension profile in order to
      prevent the occurrence of faults. However, in real annealing processes, only a
      limited number of strip tension sensors are installed along the machine
      direction. Since the effects of strip temperature, gas flow, bearing friction,
      strip inertia, and roll eccentricity can lead to nonlinear tension dynamics, it
      is difficult to apply the first-principles induced model to estimate the tension
      profile distribution. In this paper, a novel data-based hybrid tension estimation
      and fault diagnosis method is proposed to estimate the unmeasured tension between
      two neighboring rolls. The main model is established by an observer-based method
      using a limited number of measured tensions, speeds, and currents of each roll,
      where the tension error compensation model is designed by applying neural
      networks principal component regression. The corresponding tension fault
      diagnosis method is designed using the estimated tensions. Finally, the proposed
      tension estimation and fault diagnosis method was applied to a real CAPL in a
      steel-making company, demonstrating the effectiveness of the proposed method.

PMID- 21954209
TI  - Utility of fractional flow reserve to determine treatment after recent large
      myocardial infarction with severe left ventricular dysfunction.
AB  - Evaluation of ischemia and the extent of viable myocardium is required prior to
      consideration of revascularizing a lesion after a myocardial infarction in which
      there is hypo- or akinesis. We present a case in which we utilized fractional
      flow reserve (FFR) of a lesion in a patient whose nuclear study 7 days after
      infarction suggested minimal viability in the infarct zone. After FFR was
      positive, stenting was performed with recovery of a large amount of viable
      myocardium at 1 month as shown on nuclear study. This case illustrates that if
      ischemia is demonstrated by FFR in an infarct-related artery even with minimal
      viability by nuclear study, revascularization may result in significant
      myocardial recovery.

PMID- 21954211
TI  - Inhibition of terminal complement activation in severe Shiga toxin-associated HUS
      - perfect example for a fast track from bench to bedside.

PMID- 21954210
TI  - Enhancing the enzymatic digestibility of sugarcane bagasse through the
      application of an ionic liquid in combination with an acid catalyst.
AB  - Various ionic liquids have been identified as effective pretreatment solvents
      that can enhance the cellulose digestibility of lignocellulose by removing
      lignin, one of the main factors contributing to the recalcitrant nature of
      lignocellulose. 1-Butyl-3-methylimidazolium methylsulfate ([BMiM]MeSO(4)) is a
      potential delignification reagent, hence its application as a pretreatment
      solvent for sugarcane bagasse (SB) was investigated. The study also evaluated the
      benefit of an acid catalyst (i.e., H(2) SO(4)) and the effect of pretreatment
      conditions, which varied within a time and temperature range of 0-240 min and 50
      150 degrees C, respectively. The use of an acid catalyst contributed to a more
      digestible solid and a higher degree of delignification. However, the
      [BMiM]MeSO(4)-H(2) SO(4) combination failed to produce a fully digestible solid,
      as a maximum cellulose digestibility of 77% (w/w) was obtained at the optimum
      pretreatment condition of 125 degrees C for 120 min. Furthermore, up to half of
      the lignin content could be extracted during pretreatment, while simultaneously
      extensive, sometimes complete, removal of xylan, the presence of which, also
      hampers cellulose digestibility. Hence, [BMiM]MeSO(4) has been identified an
      effective pretreatment solvent for SB as the application thereof both
      significantly improved digestibility, and simultaneously removed two of the main
      factors contributing to the recalcitrant nature of lignocellulose. As xylan and
      lignin have potential value as precursor chemicals, the existing process may in
      future be extended toward substrate fractionation, a biorefinery concept where
      value is added to all feedstock constituents.

PMID- 21954212
TI  - A path to an optimal future for the Affordable Medicines Facility-malaria.

PMID- 21954213
TI  - Robust color texture features under varying illumination conditions.
AB  - Under varying illumination, both the statistical and structural contents of color
      texture are modified, leading to changes in the observed texture surface. We
      model the effect of illumination as a perturbation on an ideal color texture and
      show that the spectra of the ambient light have a significant impact on the
      observed texture patterns in the individual color channels. Motivated by studies
      in human color constancy, we propose a correlation-based transformation that
      minimizes the effect of illumination variation in color texture analysis.
      Experimental results are included, which validate the performance of the proposed
      minvariance model in the analysis of color texture.

PMID- 21954214
TI  - Cross-domain human action recognition.
AB  - Conventional human action recognition algorithms cannot work well when the amount
      of training videos is insufficient. We solve this problem by proposing a transfer
      topic model (TTM), which utilizes information extracted from videos in the
      auxiliary domain to assist recognition tasks in the target domain. The TTM is
      well characterized by two aspects: 1) it uses the bag-of-words model trained from
      the auxiliary domain to represent videos in the target domain; and 2) it assumes
      each human action is a mixture of a set of topics and uses the topics learned
      from the auxiliary domain to regularize the topic estimation in the target
      domain, wherein the regularization is the summation of Kullback-Leibler
      divergences between topic pairs of the two domains. The utilization of the
      auxiliary domain knowledge improves the generalization ability of the learned
      topic model. Experiments on Weizmann and KTH human action databases suggest the
      effectiveness of the proposed TTM for cross-domain human action recognition.

PMID- 21954215
TI  - Developing new fitness functions in genetic programming for classification with
      unbalanced data.
AB  - Machine learning algorithms such as genetic programming (GP) can evolve biased
      classifiers when data sets are unbalanced. Data sets are unbalanced when at least
      one class is represented by only a small number of training examples (called the
      minority class) while other classes make up the majority. In this scenario,
      classifiers can have good accuracy on the majority class but very poor accuracy
      on the minority class(es) due to the influence that the larger majority class has
      on traditional training criteria in the fitness function. This paper aims to both
      highlight the limitations of the current GP approaches in this area and develop
      several new fitness functions for binary classification with unbalanced data.
      Using a range of real-world classification problems with class imbalance, we
      empirically show that these new fitness functions evolve classifiers with good
      performance on both the minority and majority classes. Our approaches use the
      original unbalanced training data in the GP learning process, without the need to
      artificially balance the training examples from the two classes (e.g., via
      sampling).

PMID- 21954216
TI  - Inhibition of caspase-8 activity caused by overexpression of BCL10 contributes to
      the pathogenesis of high-grade MALT lymphoma.
AB  - BACKGROUND: Mucosa-associated lymphoid tissue (MALT) lymphoma comprises
      approximately 8% of all non-Hodgkin lymphomas and is the most common lymphoma in
      the gastro-intestinal tract. It is caused by genetic abnormalities or bacterial
      infections/chronic inflammation. B-cell lymphoma/leukemia 10 (BCL10)
      overexpression and nuclear expression have been associated with high-grade MALT
      lymphomas with genetic abnormalities that are unresponsive to Helicobacter pylori
      eradication treatment. To explore the molecular mechanism of BCL10 overexpression
      on the pathogenesis and malignant phenotype of MALT lymphoma, we generated EuSR
      BCL10 transgenic mice. PROCEDURE: By generation of heterozygous and homozygous
      EuSR-BCL10 mice and showing BCL10 expression levels in these mice, we
      quantitatively examined relation of MZ B cell expansion and inhibition of caspase
      8 activity with BCL10 protein level. We also investigated API2 and caspase-8
      expression by Western blot and their interaction with BCL10 by co
      immunoprecipitation. RESULTS: MZ B-cell expansion is directly related to BCL10
      protein level in a dose-dependent manner. The activity of caspases-8 and -3, but
      not caspase-9, was inhibited with increasing of BCL10 protein level. Expanded MZ
      B cells showed selective survival under stimulation of anti-immunoglobulin M, but
      not dexamethasone, gamma-irradiation, or anti-CD95, implying that overexpressed
      BCL10 exerts anti-apoptotic effects through B-cell antigen receptor (BCR)
      pathway. Overexpressed BCL10 protein co-immunoprecipitated with caspase-8 and
      API2 protein, suggesting an in vivo interaction of them. CONCLUSION: Our data
      demonstrate a novel effect of overexpressed BCL10 in the pathogenesis of high
      grade MALT lymphoma by increasing expression of API2 and it then forming a
      protein complex with BCL10/caspase-8 leading to caspase-8 activity suppression.

PMID- 21954217
TI  - The visual rooting reflex in individuals with autism spectrum disorders and co
      occurring intellectual disability.
AB  - The rooting reflex has long been studied by neurologists and developmentalists
      and is defined as an orientation toward tactile stimulation in the perioral
      region or visual stimulation near the face. Nearly, all previous reports of the
      visual rooting reflex (VRR) concern its presence in adults with neurological
      dysfunction. Previously, the VRR was reported to be present in a majority of
      individuals with autism and absent in control subjects. In the present larger
      study, we examined the presence of the VRR in 155 individuals with ASD and co
      occurring Intellectual Disability (ASD + ID: autism, N = 60; Pervasive
      Developmental Disorder-Not Otherwise Specified (PDD_NOS), N = 95) and in a
      contrast group of 65 individuals with ID only. The VRR was present significantly
      more often in the ASD + ID (43.9%) group than in the ID-only group (24.6%;
      chi(1)(2)= 7.19; P = 0.007). Individuals with autism displayed a VRR more often
      (55.0%) than individuals with PDD-NOS (36.8%; chi(1)(2)= 4.92; P = 0.026) and
      individuals with ID only (24.6%; chi(1)(2)= 12.09; P = 0.001). A positive VRR was
      associated with lower IQ and adaptive functioning; in the ASD + ID group, ADI
      R/ADOS domain scores were significantly higher in the VRR-positive subgroup. The
      results replicate and extend the finding of an increased occurrence of the VRR in
      autism. Although some association with IQ was observed, the VRR occurred
      substantially more often in the autism group compared with an intellectually
      disabled group, indicating some degree of specificity. Additional studies of
      infants and children with typical development, ASD and ID are needed to determine
      the utility of the VRR in ASD risk assessment and to elucidate possible specific
      behavioral associations.

PMID- 21954218
TI  - Osteogenic gene expression of canine bone marrow stromal cell and bacterial
      adhesion on titanium with different nanotubes.
AB  - Bacterial infection and osseointegration of implant-biomaterials all play
      important roles in the success of an orthopedic prosthesis or a dental-implant.
      In this work, we evaluated the osteogenic gene expression of canine bone marrow
      stromal cells (CBMSCs) and the adhesion of Staphylococcus aureus (ATCC 12598) on
      different diameter TiO(2) nanotube layers. The CBMSCs cultured on 30 and 70 nm
      nanotubes displayed polygon shape, but obviously elongated when the diameter of
      nanotubes turned to 120 nm. A significant increase in CBMSCs proliferation by as
      much as about ~300%, and osteogenic gene (RUNX-2, OPN, COL-1, and OCN) expression
      were observed on the 120 nm diameter nanotubes when compared to the smooth Ti.
      However, the adhesion of bacteria also increased with an increased tube diameter
      and reached highest value on 120 nm nanotubes after 4 h of incubation. ~300-400%
      increase in bacterial attached to 120 nm nanotubes in contract to the smooth Ti.
      These data suggested reducing bacteria colonization should be considered when
      larger diameter nanotubes with better osteogenic property would be used as
      orthopedic implants or dental implants.

PMID- 21954219
TI  - Cardiovascular modeling of congenital heart disease based on neonatal
      echocardiographic images.
AB  - This paper proposes a 3-D cardiovascular modeling system based on neonatal
      echocardiographic images. With the system, medical doctors can interactively
      construct patient-specific cardiovascular models, and share the complex topology
      and the shape information. For the construction of cardiovascular models with a
      variety of congenital heart diseases, we propose a set of algorithms and
      interface that enable editing of the topology and shape of the 3-D models. In
      order to facilitate interactivity, the centerline and radius of the vessels are
      used to edit the surface of the heart vessels. This forms a skeleton where the
      centerlines of blood vessel serve as the nodes and edges, while the radius of the
      blood vessel is given as an attribute value to each node. Moreover, parent-child
      relationships are given to each skeleton. They are expressed as the directed
      acyclic graph, where the skeletons are viewed as graph nodes and the connecting
      points are graph edges. The cardiovascular models generated from some patient
      data confirmed that the developed technique is capable of constructing
      cardiovascular disease models in a tolerable timeframe. It is successful in
      representing the important structures of the patient-specific heart vessels for
      better understanding in preoperative planning and electric medical recording of
      the congenital heart disease.

PMID- 21954220
TI  - Joint-pain comorbidity, health status, and medication use in hip and knee
      osteoarthritis: a cross-sectional study.
AB  - OBJECTIVE: To determine the prevalence of joint-pain comorbidities in individuals
      with hip or knee osteoarthritis (OA) and to assess the differences in the
      characteristics of people with and without joint-pain comorbidities. METHODS: In
      this cross-sectional study, individuals referred to secondary care for treatment
      of hip/knee OA completed questionnaires to determine sociodemographic
      characteristics, disease-related outcomes, and joint-pain comorbidities. Joint
      pain comorbidity was defined as pain perceived in a joint, other than the index
      joint, for more than half of the days in the preceding month. To compare
      differences in patient- and disease-related characteristics between participants
      with and without joint-pain comorbidities, we performed analyses of covariance
      and logistic regression. RESULTS: A total of 401 individuals, 117 with hip OA and
      284 with knee OA, returned the questionnaire (82% response rate); the mean +/- SD
      age was 58 +/- 13 years and 58% of the responders were women. Fifty-eight percent
      of the participants reported symptoms in >=1 other joint. Participants with joint
      pain comorbidities were more likely to be women, less educated, and have more
      medical comorbidities. Individuals with joint-pain comorbidities reported
      unfavorable outcomes on pain, functioning, fatigue, distress, and health-related
      quality of life compared with patients without joint-pain comorbidities (P <
      0.001 for all). Moreover, use of nonsteroidal antiinflammatory drugs (P = 0.038),
      opioids (P = 0.010), and supplements (P = 0.019) was higher in the group with
      joint-pain comorbidities. CONCLUSION: Our results indicate that individuals with
      joint-pain comorbidities represent a clinically relevant and large subgroup of
      people with OA of the knee or hip. We recommend addressing joint-pain
      comorbidities in both research and clinical practice.

PMID- 21954221
TI  - Crosstalk between leptin and interleukin-1beta abrogates negative inotropic
      effects in a model of chronic hyperleptinemia.
AB  - Interleukin 1 beta (IL-1beta) is a proinflammatory cytokine with potent
      cardiosuppressive effects. Previous studies have shown that leptin blunts the
      negative inotropic effects of IL-1beta in isolated adult rat cardiac myocytes.
      However, the interactions between leptin and IL-1beta in the heart have not been
      examined on a background of chronic hyperleptinemia. To study this interaction,
      we have chosen the SHHF rat, a model of spontaneous hypertension that ultimately
      develops congestive heart failure. SHHF that are heterozygous for a null mutation
      of the leptin receptor (+/fa(cp), HET) are phenotypically lean but chronically
      hyperleptinemic and develop heart failure earlier than their normoleptinemic true
      lean (+/+, LN) littermates. Simultaneous cell shortening and calcium transients
      were measured in isolated ventricular cardiac myocytes from LN and HET SHHF in
      response to leptin, IL-1beta or IL-1beta following one hour pretreatment with
      leptin. Despite evidence of metabolic leptin resistance, HET myocytes were
      sensitive to the negative inotropic effect of leptin, similar to LN.
      Contractility returned to control levels in myocytes from HET that were
      pretreated with leptin prior to IL-1beta, while contractility remained depressed
      compared with control and similar to leptin alone in LN. Chronic hyperleptinemia
      resulted in altered JAK/STAT signaling in response to leptin and IL-1beta in
      isolated perfused hearts from HET compared with LN SHHF. Phosphorylated STAT3
      (pSTAT3) and STAT5 (pSTAT5) decreased when HET hearts were treated with leptin
      followed by IL-1beta. While decreases in pSTAT3 and pSTAT5 may be associated with
      abrogation of the acute negative inotropic effects of IL-1beta in the presence of
      leptin in HET, long-term consequences remain to be explored. This study
      demonstrates that the heart remains sensitive to leptin in a hyperleptinemic
      state. Crosstalk between leptin and IL-1beta can influence cardiac function and
      cytokine signaling and these interactions are moderated by the presence of long
      term hyperleptinemia.

PMID- 21954222
TI  - Recombinant human midkine stimulates proliferation and decreases
      dedifferentiation of auricular chondrocytes in vitro.
AB  - Autologous chondrocyte implantation (ACI) is widely used for the repair of
      cartilage defects. However, due to the lack of chondrocyte growth factor and
      dedifferentiation of the cultured primary chondrocytes, cell source has limited
      the clinical potential of ACI. Auricular cartilage is an attractive potential
      source of cells for cartilage tissue engineering. Here we demonstrated that
      recombinant human midkine (rhMK) significantly promoted proliferation of rat
      primary auricular chondrocytes cultured and passaged in monolayer, which was
      mediated by the activation of mitogen-activated protein kinase and
      phosphoinositide 3-kinase pathways. Furthermore, rhMK attenuated the
      dedifferentiation of cultured chondrocytes by maintaining the expression of
      chondrocyte-specific matrix proteins during culture expansion and passage.
      Importantly, rhMK-expanded chondrocytes reserved their full chondrogenic
      potential and redifferentiated into elastic chondrocytes after being cultured in
      high density. The results suggest that rhMK may be used for the preparation of
      chondrocytes in cartilage tissue engineering.

PMID- 21954223
TI  - Fluorinert, an oxygen carrier, improves cell culture performance in deep square
      96-well plates by facilitating oxygen transfer.
AB  - In bioprocess development, the 96-well plate format has been widely used for high
      throughput screening of production cell line or culture conditions. However,
      suspension cell cultures in conventional 96-well plates often fail to reach high
      cell density under normal agitation presumably due to constraints in oxygen
      transfer. Although more vigorous agitation can improve gas transfer in 96-well
      plate format, it often requires specialized instruments. In this report, we
      employed Fluorinert, a biologically inert perfluorocarbon, to improve oxygen
      transfer in 96-well plate and to enable the growth of a Chinese Hamster Ovary
      cell line expressing a recombinant monoclonal antibody. When different amounts of
      Fluorinert were added to the cell culture medium, a dose-dependent improvement in
      cell growth was observed in both conventional and deep square 96-well plates.
      When sufficient Fluorinert was present in the culture, the cell growth rate, the
      peak cell density, and recombinant protein production levels achieved in deep
      square 96-wells were comparable to cultures in ventilated shake flasks. Although
      Fluorinert is known to dissolve gases such as oxygen and CO(2), it does not
      dissolve nor extract medium components, such as glucose, lactate, or amino acids.
      We conclude that mixing Fluorinert with culture media is a suitable model for
      miniaturization of cell line development and process optimization. Proper cell
      growth and cellular productivity can be obtained with a standard shaker without
      the need for any additional aeration or vigorous agitation.

PMID- 21954224
TI  - Abusive head trauma: recognition and the essential investigation.
AB  - Abusive head trauma (AHT) affects one in 4000-5000 infants every year and is one
      of the most serious forms of physical child abuse that has a high associated
      mortality and morbidity. Differentiating this form of abuse from another
      potential cause of brain injury is of utmost importance to the welfare of the
      child concerned and it is essential that the condition is correctly diagnosed.
      This article describes the evidence base behind the associated historical,
      clinical and neuroradiological features of AHT and spinal injury in physical
      abuse and sets out an algorithm of essential investigations that should be
      performed in any infant or young child where AHT is suspected.

PMID- 21954225
TI  - Akt activation is responsible for enhanced migratory and invasive behavior of
      arsenic-transformed human bronchial epithelial cells.
AB  - BACKGROUND: Arsenic is one of the most common environmental contaminants. Long
      term exposure to arsenic causes human bronchial epithelial cell (HBEC) malignant
      transformation and lung cancer. However, the mechanism of arsenic lung
      carcinogenesis is not clear, and the migratory and invasive properties of arsenic
      transformed cells (As-transformed cells) have rarely been studied. OBJECTIVES:
      This study was designed to investigate the migratory and invasive behavior of As
      transformed HBECs and the underlying mechanism. METHODS: As-transformed
      p53lowHBECs were generated by exposing p53-knockdown HBECs to sodium arsenite
      (2.5 MUM) for 16 weeks. Cell migration was assessed by transwell migration and
      wound-healing assay. Cell invasion was evaluated using Matrigel-coated transwell
      chambers. Gene overexpression, small interfering RNA (siRNA) knockdowns, and
      pharmacological inhibitors were used to determine the potential mechanism
      responsible for enhanced cell migration and invasion. RESULTS: Transwell
      migration and invasion assays revealed that As-transformed p53lowHBECs were
      highly migratory and invasive. Akt (also known as protein kinase B) and
      extracellular signal-regulated protein kinase 1/2 (Erk1/2) were strongly
      activated in As-transformed p53lowHBECs. Stable expression of microRNA 200b in As
      transformed p53lowHBECs abolished Akt and Erk1/2 activation and completely
      suppressed cell migration and invasion. Pharmacological inactivation of Akt but
      not Erk1/2 significantly decreased cell migration and invasion. Inhibition of Akt
      reduced the expression of epithelial-to-mesenchymal transition-inducing
      transcription factors zinc-finger E-box-binding homeobox factor 1 (ZEB1) and
      ZEB2. siRNA knockdown of ZEB1 and ZEB2 impaired As-transformed p53lowHBEC
      migration and invasion. CONCLUSIONS: Akt activation plays a critical role in
      enabling As-transformed HBEC migration and invasion by promoting ZEB1 and ZEB2
      expression.

PMID- 21954227
TI  - Diagnosing diabetes on admission hyperglycaemia.

PMID- 21954226
TI  - Evolution of disease burden over five years in a multicenter inception systemic
      lupus erythematosus cohort.
AB  - OBJECTIVE: We describe disease activity, damage, and the accrual of key
      autoantibodies in an inception systemic lupus erythematosus (SLE) cohort.
      METHODS: The Systemic Lupus International Collaborating Clinics (SLICC)
      International Research Network, comprising 27 centers from 11 countries, has
      followed an inception cohort of SLE patients yearly according to a standardized
      protocol. Of these patients, 298 were followed for a minimum of 5 years and
      constitute the study population. Disease activity was assessed using the SLE
      Disease Activity Index 2000 (SLEDAI-2K) and damage was assessed using the
      SLICC/American College of Rheumatology Damage Index (SDI). Antinuclear antibody
      (ANA), anti-DNA, and anticardiolipin antibody (aCL) levels and lupus
      anticoagulant were assessed yearly. Descriptive statistics were generated and
      repeated-measures general linear models were used to evaluate SLEDAI-2K and SDI
      over time between whites and nonwhites. RESULTS: Of the 298 patients, 87% were
      women, 55% were white, 12% were African American, 14% were Asian, 16% were
      Hispanic, and 2% were categorized as "other." At enrollment, the mean age was
      35.3 years, the mean SLEDAI-2K score was 5.9, and the mean disease duration was
      5.5 months. Mean SLEDAI-2K scores decreased in the first year and then remained
      low. SLEDAI-2K scores were significantly lower at each year in whites compared to
      nonwhites. Mean SDI scores increased progressively over 5 years; there was no
      significant difference between whites and nonwhites. As expected, ANA positivity
      was high and anti-DNA positivity was relatively low at enrollment, and both
      increased over 5 years. Although lupus anticoagulant increased slightly over 5
      years, aCL positivity did not. CONCLUSION: Disease activity in newly diagnosed
      patients decreases over their first 5 years, while damage increases. Antibody
      positivity ran variable courses over this period.

PMID- 21954228
TI  - Clinical outcomes in non-surgically managed patients with very severe versus
      severe aortic stenosis.
AB  - OBJECTIVE: The management of asymptomatic severe and very severe aortic stenosis
      (AS) remains unestablished. This study aimed to investigate the clinical outcomes
      of severe versus very severe AS patients. DESIGN: A single centre, retrospective
      cohort study. PATIENTS AND METHODS: The study retrospectively reviewed 108
      conservatively treated patients with severe AS (a maximal jet velocity >= 4.0
      m/s, or mean aortic pressure gradient (MPG) >= 40 mm Hg, or an aortic valve area
      (AVA) <1.0 cm(2)) and 58 patients with very severe AS (a maximal jet velocity >=
      5.0 m/s, or MPG >= 50 mm Hg or an AVA <0.6 cm(2)). Clinical outcomes were
      compared between the two groups, considering the existence of symptoms. MAIN
      OUTCOME MEASURES: All-cause mortality and valve-related event, defined by a
      composite of cardiac death and hospitalisation because of heart failure. RESULTS:
      Mean follow-up was 5.5 +/- 3.1 years. Fifty-six patients (52%) with severe AS and
      20 patients (34%) with very severe AS were asymptomatic. Very severe AS had
      poorer survival and valve-related event-free survival than severe AS at 3 years
      (77% vs 88%, p < 0.01; 75% vs 88%, p < 0.001, respectively). In addition, the 3
      year survival and valve-related event-free survival of asymptomatic very severe
      AS were comparable with symptomatic severe AS, but they were significantly worse
      than asymptomatic severe AS (p < 0.01 and p < 0.001, respectively). CONCLUSIONS:
      Surgery should always be considered in very severe AS regardless of symptoms, and
      particular attention needs to be paid to their extremely poor outcomes.

PMID- 21954230
TI  - Carotid artery stenting, what can be learned after more than 1,000 patients: a
      single centre single operator experience.
AB  - AIMS: The aim of the present study was to evaluate the outcome of carotid artery
      stenting (CAS) in a single, high-volume centre of a single operator and to
      analyse the circumstances under which complications occur. Recent trials
      comparing CAS with carotid endarterectomy demonstrated controversial results. The
      low experience of interventionists in performing CAS was a major limitation of
      these studies. The number of procedures needed to achieve optimal skills is
      unknown. METHODS AND RESULTS: From May 1997 until April 2010, 1,004 patients with
      symptomatic or asymptomatic carotid artery stenosis underwent CAS by a single
      operator. A cerebral protection device was in mandatory use since 2000. In
      hospital complication rates were defined as the cumulative rate of death,
      myocardial infarction or stroke. Procedural success was achieved in 97.77% of
      patients. The perioperative complication rate was 1.69% including 0.2% deaths,
      1.1% patients with minor stroke, 0.4% patients with major stroke. In 88% (15 out
      of 17) of the patients with complications, unfavourable anatomical or procedural
      factors could be identified. After the first 100 CAS performed,the complication
      rate was at 3% and significantly decreased to 1% after more than 500 procedures.
      Patients >=80 years had a significantly higher complication rate. CONCLUSIONS: In
      a high-volume experienced centre, the in-hospital complication rate is low.
      Complications occurred almost exclusively in patients with unfavourable
      anatomical or procedural characteristics and seem to be avoidable in most
      patients. A learning curve was observed up to 500 procedures. Elderly patients
      have a higher complication rate.

PMID- 21954232
TI  - Do market fees differ from relative value scale fees? Examining surgeon payments
      in New Zealand.
AB  - OBJECTIVES: Health funders face the challenge of determining the appropriate
      level of surgeon fees in fee-for-service schemes.  A resource-based relative
      value scale (RBRVS) attempts to identify the fees that would exist in a
      competitive market.  Private insurance providers in New Zealand do not use a
      RBRVS but rather rely on a market.  We explore the extent to which private
      surgeon fees in New Zealand are consistent with fees that would be generated by a
      RBRVS. METHODS: Data on 155,290 surgical procedures from 2004-06 were provided by
      New Zealand's largest private health insurer.  314 procedure codes were matched
      to the Australian Ministry of Health and Ageing's RBRVS. A random effects model
      determined predicted surgeon reimbursements based on the RBRVS, the location and
      the year. Procedure volume and specialty were explored as potential sources of
      deviations. RESULTS: The RBRVS, location and year explain 79% of the variation in
      surgeon fees. After accounting for the RBRVS, location and year, no statistical
      differences were found between five out of the seven specialties, but higher
      volume procedures were associated with lower fees. There was some evidence that
      the model explained less variation in lower volume procedures. CONCLUSIONS:
      Surgical fees were generally consistent with those predicted by the RBRVS.
      However, the fees for high volume procedures were relatively lower than predicted
      while the fees for low volume procedures appeared more variable. The findings are
      consistent with the hypothesis that market forces lowered prices for procedures
      with higher volumes. This has implications for how health funders might determine
      private surgical fees, especially in mixed public-private systems.

PMID- 21954231
TI  - IRE1 plays an essential role in ER stress-mediated aggregation of mutant
      huntingtin via the inhibition of autophagy flux.
AB  - Huntington's disease (HD), an inherited neurodegenerative disorder, is caused by
      an expansion of cytosine-adenine-guanine repeats in the huntingtin gene. The
      aggregation of mutant huntingtin (mtHTT) and striatal cell loss are
      representative features to cause uncontrolled movement and cognitive defect in
      HD. However, underlying mechanism of mtHTT aggregation and cell toxicity remains
      still elusive. Here, to find new genes modulating mtHTT aggregation, we performed
      cell-based functional screening using the cDNA expression library and isolated
      IRE1 gene, one of endoplasmic reticulum (ER) stress sensors. Ectopic expression
      of IRE1 led to its self-activation and accumulated detergent-resistant mtHTT
      aggregates. Treatment of neuronal cells with ER stress insults, tunicamycin and
      thapsigargin, increased mtHTT aggregation via IRE1 activation. The kinase
      activity of IRE1, but not the endoribonuclease activity, was necessary to
      stimulate mtHTT aggregation and increased death of neuronal cells, including SH
      SY5Y and STHdhQ111/111 huntingtin knock-in striatal cells. Interestingly, ER
      stress impaired autophagy flux via IRE1-TRAF2 pathway, thus enhancing cellular
      accumulation of mtHTT. Atg5 deficiency in M5-7 cells increased mtHTT aggregation
      but blocked ER stress-induced mtHTT aggregation. Further, ER stress markers
      including p-IRE1 and autophagy markers such as p62 were up-regulated exclusively
      in the striatal tissues of HD mouse models and in HD patients. Moreover, down
      regulation of IRE1 expression rescues the rough-eye phenotype by mtHTT in a HD
      fly model. These results suggest that IRE1 plays an essential role in ER stress
      mediated aggregation of mtHTT via the inhibition of autophagy flux and thus
      neuronal toxicity of mtHTT aggregates in HD.

PMID- 21954229
TI  - Assessment of health-related quality of life as an outcome measure in
      granulomatosis with polyangiitis (Wegener's).
AB  - OBJECTIVE: To assess a generic measure of health-related quality of life (HRQOL)
      as an outcome measure in granulomatosis with polyangiitis (Wegener's) (GPA).
      METHODS: Subjects were participants in the Wegener's Granulomatosis Etanercept
      Trial (WGET) or the Vasculitis Clinical Research Consortium Longitudinal Study
      (VCRC-LS). HRQOL was assessed with the Short Form 36 (SF-36) health survey that
      includes physical and mental component summary scores (PCS and MCS,
      respectively). Disease activity was assessed with the Birmingham Vasculitis
      Activity Score for Wegener's Granulomatosis (BVAS/WG). RESULTS: The data from 180
      subjects in the WGET (median followup 2.3 years, mean number of visits 10) and
      237 subjects in the VCRC-LS (median followup 2.0 years, mean number of visits 8)
      were analyzed. A 1 unit increase in the BVAS/WG corresponded to a 1.15 unit (95%
      confidence interval [95% CI] 1.02, 1.29) decrease for the PCS and a 0.93 (95% CI
      0.78, 1.07) decrease for the MCS in the WGET, and to a 1.16 unit decrease for the
      PCS (95% CI 0.94, 1.39) and a 0.79 unit decrease for the MCS (95% CI 0.51, 1.39)
      in the VCRC-LS. In both arms of the WGET study, SF-36 measures improved rapidly
      during the first 6 weeks of treatment followed by gradual improvement among
      patients achieving sustained remission (0.5 improvement in PCS per 3 months), but
      worsened slightly (0.03 decrease in PCS every 3 months) among patients not
      achieving sustained remission (P = 0.005). CONCLUSION: HRQOL, as measured by the
      SF-36, is reduced among patients with GPA. SF-36 measures are modestly associated
      with other disease outcomes and discriminate between disease states of importance
      in GPA.

PMID- 21954233
TI  - We can't afford my chronic illness! The out-of-pocket burden associated with
      managing chronic obstructive pulmonary disease in western Sydney, Australia.
AB  - OBJECTIVES: To examine the household economic consequences that are associated
      with out-of-pocket spending for the care and management of chronic obstructive
      pulmonary disease (COPD). METHODS: A cross-sectional study. A self-administered
      questionnaire was posted to all patients enrolled (n = 656) in the Respiratory
      Ambulatory Care Service in western Sydney, Australia, between 1 January 2001 and
      31 August 2008. Two hundred and eighteen completed questionnaires were received.
      RESULTS: One hundred and sixty-nine (78%) respondents experienced economic
      hardship while managing their illness. Fifty-nine (27%) reported being unable to
      pay for medical or dental expenses, 38 (18%) were unable to pay for medication,
      59 (27%) were unable to pay rent or mortgage and 40 (19%) were unable to pay
      utility bills. Respondents experiencing economic hardship paid more out-of-pocket
      overall (=AUD$544 versus =AUD$280; t(148) = -2.03, P = 0.04) and for medications
      and oxygen specifically (=AUD$247 versus =AUD$125; t(83) = -3.98, P < 0.0001).
      Fifty-six (46%) respondents had catastrophic levels of out-of-pocket spending
      which made them 7.5 times more likely to experience economic hardship (95%
      confidence interval [CI]: 1.2-46.3). CONCLUSIONS: The costs associated with
      living with COPD make it difficult for patients and their families to afford
      necessary living expenses while also paying health care expenses. This is
      alarming within Australia where a well-funded universal health insurance system
      is in place. Rising co-payments for medications and private medical
      consultations, poorly subsidised health support (e.g. home oxygen), non-health
      logistics (e.g. transport) and eligibility barriers for existing social support
      are making chronic illness management seriously economically stressful,
      especially for those with low incomes, including the retired.

PMID- 21954234
TI  - Myth: the ageing population is to blame for uncontrollable health care costs.

PMID- 21954235
TI  - Are NHS foundation trusts able and willing to exercise autonomy? 'You can take a
      horse to water...'.
AB  - Foundation trusts (FTs) have been a central part of the government's National
      Health Service (NHS) reforms in England since 2004. They illustrate the
      government's claim to decentralization, by granting greater autonomy to high
      performing organizations. The number of FTs has grown steadily, reaching 131 in
      September 2010, over 50% of eligible trusts. Despite this growth, and
      notwithstanding the fact that organizations which initially became FTs were
      previously high performing, doubts remain about the implementation of the FT
      policy. This article examines the implementation of FTs in the NHS and focuses on
      the nature and exercise of autonomy by FTs. It argues that the ability of FTs to
      exercise autonomy is in place, but the (relatively limited) extent of
      implementation may be explained by trusts' lack of willingness to exercise such
      autonomy. Such unwillingness may be because of continued centralization, unclear
      policy and financial regimes, fear of negative impacts on relations with other
      local organizations, and awareness of greater risk to the FT, among others.
      Addressing the tension between FTs' ability and willingness to exercise autonomy
      will largely explain the extent to which the government's provider side reforms
      will be implemented.

PMID- 21954236
TI  - 'Bending the cost curve' and the politics of cost control.

PMID- 21954238
TI  - Technology in context.

PMID- 21954237
TI  - Evidence for the credibility of health economic models for health policy decision
      making: a systematic literature review of screening for abdominal aortic
      aneurysms.
AB  - OBJECTIVE: To investigate whether the credibility of health economic models of
      screening for abdominal aortic aneurysms for health policy decision-making has
      improved since 2005 when a systematic review by Campbell et al. concluded that
      reporting standards were poor and there was divergence between the findings of
      studies that was hard to explain. METHODS: A systematic literature review was
      carried out following PRISMA reporting principles. Health economic models of the
      cost-effectiveness of screening for abdominal aortic aneurysms published between
      2005-2010 were included. Key characteristics were extracted and the models were
      assessed for quality against guidelines for best practice by a multidisciplinary
      team. RESULTS: Seven models were identified and found to provide divergent
      guidance. Only three reports met 10 of the 15 quality criteria. CONCLUSIONS:
      Researchers in the field seem to have benefited from general advances in health
      economic modelling and some improvements in reporting were noted. However, the
      low level of agreement between studies in model structures and assumptions, and
      difficulty in justifying these (convergent validity), remain a threat to the
      credibility of health economic models. Decision-makers should not accept the
      results of a modelling study if the methods are not fully transparent and
      justified. Modellers should, whenever relevant, supplement a primary report of
      results with a technical report detailing and discussing the methodological
      choices made.

PMID- 21954240
TI  - Elimination of rubella and congenital rubella syndrome: we did it together!
      Foreword.

PMID- 21954239
TI  - Negative stereotype activation alters interaction between neural correlates of
      arousal, inhibition and cognitive control.
AB  - Priming negative stereotypes of African Americans can bias perceptions toward
      novel Black targets, but less is known about how these perceptions ultimately
      arise. Examining how neural regions involved in arousal, inhibition and control
      covary when negative stereotypes are activated can provide insight into whether
      individuals attempt to downregulate biases. Using fMRI, White egalitarian
      motivated participants were shown Black and White faces at fast (32 ms) or slow
      (525 ms) presentation speeds. To create a racially negative stereotypic context,
      participants listened to violent and misogynistic rap (VMR) in the background. No
      music (NM) and death metal (DM) were used as control conditions in separate
      blocks. Fast exposure of Black faces elicited amygdala activation in the NM and
      VMR conditions (but not DM), that also negatively covaried with activation in
      prefrontal regions. Only in VMR, however, did amygdala activation for Black faces
      persist during slow exposure and positively covary with activation in
      dorsolateral prefrontal cortex while negatively covarying with activation in
      orbitofrontal cortex. Findings suggest that contexts that prime negative racial
      stereotypes seem to hinder the downregulation of amygdala activation that
      typically occurs when egalitarian perceivers are exposed to Black faces.

PMID- 21954241
TI  - Rubella and congenital rubella syndrome elimination: lessons learned for the
      future. Preface.

PMID- 21954249
TI  - Elimination of rubella and congenital rubella syndrome in the Americas.
AB  - In 2003, the Pan American Health Organization (PAHO) adopted a resolution calling
      for rubella and congenital rubella syndrome (CRS) elimination in the Americas by
      the year 2010. To accomplish this goal, PAHO advanced a rubella and CRS
      elimination strategy including introduction of rubella-containing vaccines into
      routine vaccination programs accompanied by high immunization coverage,
      interruption of rubella transmission through mass vaccination of adolescents and
      adults, and strengthened surveillance for rubella and CRS. The rubella
      elimination strategies were aligned with the successful measles elimination
      strategies. By the end of 2009, all countries routinely vaccinated children
      against rubella, an estimated 450 million people had been vaccinated against
      measles and rubella in supplementary immunization activities, and rubella
      transmission had been interrupted. This article describes how the region
      eliminated rubella and CRS.

PMID- 21954250
TI  - Global use of rubella vaccines, 1980-2009.
AB  - In most developing countries, rubella vaccine has not been included in the
      Expanded Programme on Immunization because of lack of information on the burden
      of disease caused by rubella virus, increased cost associated with adding rubella
      vaccine, and the concern that if high vaccine coverage cannot be achieved and
      maintained, the risk of congenital rubella syndrome (CRS) may increase. Data for
      2009 reported by countries to the World Health Organization (WHO) and United
      Nations Children's Fund through the annual Joint Reporting Form were used to
      indicate patterns in the worldwide use of rubella vaccines, describe the number
      of reported rubella and CRS cases by WHO Region, and explore factors associated
      with decisions by countries to introduce rubella vaccine in their national
      childhood immunization programs. The number of WHO Member States using rubella
      containing vaccine (RCV) in their national childhood immunization schedule
      increased from 83 (43%) in 1996 to 130 (67%) in 2009. Although scheduled ages for
      rubella vaccination vary across countries and regions, most countries have a 2
      dose schedule using a combined measles-mumps-rubella vaccine. Among 130 countries
      using RCV in 2009, median coverage with the first dose of measles-containing
      vaccine (MCV1) was 95% (interquartile range [IQR], 90%-98%), compared with a
      median MCV1 coverage of 76% (IQR, 64%-88%) in countries not using RCV. The median
      per capita gross national income among 130 countries using RCV was US $6300 (IQR,
      $3227-$20 916), compared with $635 (IQR, $337-$1027) for 63 countries not using
      RCV. In 2009, 121 344 rubella cases from 167 countries were reported to WHO.
      However, only 165 CRS cases were reported globally, of which 67 were in the
      Eastern Mediterranean Region. Further improvements in surveillance are needed to
      better document the burden of CRS, and new financing mechanisms will be required
      to catalyze the introduction of rubella vaccine in developing countries that
      currently meet the coverage criteria for introduction of rubella vaccine.

PMID- 21954251
TI  - Rubella elimination, the Canadian experience.
AB  - Surveillance and outbreak data were reviewed to demonstrate interruption and
      elimination of indigenous rubella virus transmission in Canada. Rubella
      elimination was defined as (1) the interruption of endemic transmission and (2)
      failure to reestablish endemic transmission within 12 months following
      importation. Data indicate that indigenous transmission of rubella has been
      interrupted following effective immunization strategies and sustained high
      vaccine coverage. However, a 2005 outbreak of rubella, following importation into
      a community that opposes immunization, demonstrates that multiple chains of
      transmission can be reestablished where pockets of low vaccine coverage exist.
      While there has been no evidence of indigenous circulation of rubella viruses
      since the 2005 outbreak, population groups with low vaccine coverage remain at
      risk following disease importation. Awareness and targeted response strategies
      for these populations, particularly in response to risks for importation, are
      important to ensure rapid detection, reporting, and effective interruption of
      transmission.

PMID- 21954252
TI  - Evidence used to support the achievement and maintenance of elimination of
      rubella and congenital rubella syndrome in the United States.
AB  - On 29 October 2004, an expert panel was convened to review the status of
      elimination of rubella and congenital rubella syndrome (CRS) in the United
      States. Primarily based on 5 types of information presented--epidemiology of
      reported cases, molecular epidemiology, seroprevalence, vaccine coverage, and
      adequacy of surveillance--the panel unanimously agreed that rubella virus is no
      longer endemic in the United States. Since 2004, new data continue to support the
      conclusion that elimination has been achieved and maintained. In documenting
      elimination in the United States, each of the 5 types of data provided evidence
      for elimination and collectively provided much stronger evidence than any one
      type could individually. As countries document the elimination of rubella and
      CRS, many sources and types of data will likely be necessary. Rigorous data
      evaluation must be conducted to look for inconsistencies among the available
      data. To maintain elimination, countries should maintain high vaccine coverage,
      adequate surveillance, and rapid response to outbreaks.

PMID- 21954253
TI  - Advocacy and resource mobilization for rubella elimination in Guatemala.
AB  - This review describes the advocacy efforts to mobilize resources for the campaign
      to vaccinate men and women aged 9-39 years, with a goal of eliminating rubella
      and congenital rubella syndrome in Guatemala. The country's investment in health
      has been historically low (0.9% of gross domestic product), and there has been a
      wide gap between the availability of economic resources and the need for economic
      resources for the immunization campaign. The review contains a summary of the
      investment made, the results of advocacy and resource mobilization, the
      vaccination coverage attained, and the campaign's impact on the disease.

PMID- 21954254
TI  - Rubella and congenital rubella syndrome elimination activities: Colombia, 2005
      2006.
AB  - As part of regional commitments in the Americas aimed at elimination of rubella
      and congenital rubella syndrome, and consolidation of measles elimination,
      Colombia conducted mass vaccination of males and females aged 14-39 years in 2005
      2006. The target population included 18,238< 443 persons (44% of the entire
      population). Vaccination activities were extended because of limited
      participation and public concerns about vaccine safety. Over a 10-month peroid,
      17,697,717 doses of measles-rubella vaccine were administered, reaching 97% of
      the target population, including 96.4% of females and 97.6% of males. Estimated
      coverage exceeded 95% in 33 of 36 departments and districts, and in 3 others, it
      ranged from 92% to 95%. In rapid monitoring conducted in 504 (45%) of 1119
      municipalities, 95% of persons in the target population were vaccinated. The
      Colombian experience underscores the importance of social mobilization at the
      local level, political commitment, and microplanning and offers lessons for
      future mass vaccination campaigns.

PMID- 21954255
TI  - Historical analysis of birth cohorts not vaccinated against rubella prior to
      national rubella vaccination campaign, Brazil.
AB  - BACKGROUND: Brazil conducted mass rubella vaccination campaigns to meet disease
      elimination goals by 2010. An analysis of rubella vaccination opportunities was
      conducted to target population groups with concentrations of unvaccinated
      individuals. METHODS: Rubella vaccination strategies for all 27 states were
      reviewed between 1992 and 2006. Yearly vaccination coverage was calculated by
      dividing number of doses of measles-rubella or measles-mumps-rubella vaccines
      administered by census estimates of target populations. For annual birth cohorts
      (1967-2005), percentages of persons not vaccinated prior to 2007 were estimated
      by subtracting the highest coverage obtained in any vaccination strategy (routine
      or campaign) from 100%. Cohort analysis results were compared with rubella
      incidence by population group. RESULTS: An estimated 28.9 million males and 7.7
      million females aged 2-40 years in 2007 remained unvaccinated against rubella,
      corresponding to 43.0% of males and 11.5% of females of these ages in Brazil. The
      highest percentages of unvaccinated birth cohorts (93.6%-98.1%) were identified
      among males aged 26-40 years. In rubella outbreaks reported during 2007, the
      highest disease incidence (22 cases per 100000 population) occurred among males
      aged 20-29 years. CONCLUSIONS: Analysis of rubella vaccination opportunities
      identified concentrations of unvaccinated adults and adolescents for targeting
      mass vaccination to eliminate rubella and congenital rubella syndrome in Brazil.

PMID- 21954256
TI  - Haiti 2007-2008 national measles-rubella vaccination campaign: implications for
      rubella elimination.
AB  - BACKGROUND: A national campaign was conducted in Haiti in 2007-2008 to vaccinate
      all children and adolescents aged 1-19 years with measles-rubella vaccine in
      support of achieving the Region of the Americas' 2010 goal of eliminating rubella
      and congenital rubella syndrome (CRS). Measles-rubella vaccine was introduced
      into the country's routine childhood immunization schedule after the campaign.
      METHODS: A nationwide, stratified, multistage cluster sample survey of 20859
      children was conducted to assess coverage using house-to-house interviews.
      RESULTS: Estimated national coverage with measles-rubella vaccine was 79.2% (95%
      confidence interval, 77.6%-80.7%), ranging from 90.2% in Nord-Ouest Department to
      70.0% in Cite Soleil Metropolitan Area. National coverage was lower for children
      aged 1-5 years (76.7%) than for those aged 6-19 years (80.3%) (P< .001) but
      similar in rural departments (79.4%) and metropolitan areas (78.6%; P = .61). The
      reasons most frequently cited for nonparticipation in the campaign were that the
      child was ill or unavailable (18.6%), did not know vaccinations were important
      (13.8%), did not know when to go or forgot to go (13.3%), and did not have enough
      time (12.3%). CONCLUSIONS: The measles-rubella vaccination campaign was critical
      for raising rubella immunity levels in children and adolescents in Haiti. To
      remain free of rubella transmission and CRS, Haiti must also achieve and sustain
      high routine measles-rubella vaccination coverage and maintain high-quality
      integrated measles-rubella and CRS surveillance, including laboratory-based
      confirmation for reported rash illnesses. If routine measles-rubella vaccination
      coverage is suboptimal or if gaps in coverage are identified, additional mass
      campaigns with measles-rubella vaccine will be necessary.

PMID- 21954257
TI  - Lessons learned from integrated surveillance of measles and rubella in the
      Caribbean.
AB  - The Caribbean subregion was one of the first areas to successfully integrate
      measles and rubella surveillance, and it can serve as an example to other
      subregions on how to achieve similar success. The integrated surveillance system,
      established through strong political commitment by Caribbean countries, is
      coordinated by the Caribbean Epidemiology Centre (CAREC). The system, which
      became operational in January 2000, is designed to detect and investigate
      patients with fever and rash illness, and also test a blood specimen from each
      case investigated. During over 9 years of operation, 3733 cases were reported and
      investigated. Laboratory tests identified 2 imported cases of measles, 27 cases
      of rubella, 309 cases of dengue, and 260 cases of human herpesvirus 6 (HHV-6)
      infection. The lessons learned from the success of this integrated system
      indicate that the following factors are critical: strong political commitment,
      strong technical oversight from all levels within the health-care system, the use
      of proven tools or systems and technology for data collection and analysis,
      integration with other surveillance activities, continuing training, and
      continuing review and evaluation.

PMID- 21954259
TI  - Congenital rubella syndrome surveillance in Honduras.
AB  - INTRODUCTION: Congenital rubella syndrome (CRS) surveillance was established in
      Honduras to determine the scope of the problem and assess the impact of
      vaccination. METHODS: Implementation of the surveillance system required the
      drafting of national CRS epidemiological surveillance guidelines, the development
      of a laboratory diagnostic method, and training of physicians, nurses, and
      microbiologists in the Honduran hospital network and social security system on
      CRS surveillance guidelines. RESULTS: Honduras' experience with the surveillance
      of other vaccine-preventable diseases facilitated the implementation of hospital
      based CRS surveillance. The surveillance system operates in 23 of the 25 public
      hospitals that offer services to children and at 2 social security hospitals; the
      private sector has not been integrated into this system. Clinical and technical
      staff, including representatives from various disciplines such as pediatrics,
      neonatology, general medicine, epidemiology, nursing, and microbiology,
      participate in the hospital network, as well as follow up on cases in accordance
      with the standardized guidelines, depending on their areas of expertise.
      CONCLUSIONS: Implementation of the CRS surveillance system requires technical
      guidelines, laboratory diagnostic capacity, and trained multidisciplinary human
      resources for its systematization and operation.

PMID- 21954258
TI  - Etiologies of rash and fever illnesses in Campinas, Brazil.
AB  - BACKGROUND: Few population-based studies of infectious etiologies of fever-rash
      illnesses have been conducted. This study reports on enhanced febrile-rash
      illness surveillance in Campinas, Brazil, a setting of low measles and rubella
      virus transmission. METHODS: Cases of febrile-rash illnesses in individuals aged
      <40 years that occurred during the period 1 May 2003-30 May 2004 were reported.
      Blood samples were collected for laboratory diagnostic confirmation, which
      included testing for adenovirus, dengue virus, Epstein-Barr virus (EBV),
      enterovirus, human herpes virus 6 (HHV6), measles virus, parvovirus-B19,
      Rickettsia rickettsii, rubella virus, and group A streptococci (GAS) infections.
      Notification rates were compared with the prestudy period. RESULTS: A total of
      1248 cases were notified, of which 519 (42%) had laboratory diagnosis. Of these,
      HHV-6 (312 cases), EBV (66 cases), parvovirus (30 cases), rubella virus (30
      cases), and GAS (30 cases) were the most frequent causes of infection. Only 10
      rubella cases met the rubella clinical case definition currently in use.
      Notification rates were higher during the study than in the prestudy period (181
      vs 52.3 cases per 100,000 population aged <40 years). CONCLUSIONS: Stimulating a
      passive surveillance system enhanced its sensitivity and resulted in additional
      rubella cases detected. In settings with rubella elimination goals, rubella
      testing may be considered for all cases of febrile-rash illness, regardless of
      suspected clinical diagnosis.

PMID- 21954260
TI  - Enhanced surveillance for congenital rubella syndrome following mass rubella
      vaccination of girls and reproductive-aged women.
AB  - Chile was the first country in the Americas to conduct surveillance for
      congenital rubella syndrome (CRS) as part of screening for common causes of
      congenital birth defects (referred to as TORCH pathogens). The surveillance
      system identified 15 CRS cases in 1999 and 2 cases in 2000, and it has identified
      no CRS cases since 2000. CRS surveillance in Chile meets recommended surveillance
      standards and may serve as a model for CRS surveillance in other countries.

PMID- 21954261
TI  - Virologic surveillance for wild-type rubella viruses in the Americas.
AB  - The goal of eliminating rubella from the Americas by 2010 was established in
      2003. Subsequently, a systematic nomenclature for wild-type rubella viruses
      (wtRVs) was established, wtRVs circulating in the region were catalogued, and
      importations of wtRVs into a number of countries were documented. The geographic
      distribution of wtRVs of various genotypes in the Americas, interpreted in the
      context of the global distribution of these viruses, contributed to the
      documentation of rubella elimination from some countries. Data from virologic
      surveillance also contributed to the conclusion that viruses of genotype 2B began
      circulating endemically in the Americas during 2006-2007. Viruses of one genotype
      (1C), which are restricted to the Americas, will likely disappear completely from
      the world as they are eliminated from the Americas. Efforts to expand virologic
      surveillance for wtRVs in the Americas will also provide additional data aiding
      the elimination of rubella from the region. For example, identification of
      vaccine virus in specimens from rash and fever cases found during elimination can
      identify such cases as vaccine associated.

PMID- 21954262
TI  - Enhanced laboratory surveillance for the elimination of rubella and congenital
      rubella syndrome in the Americas.
AB  - One of the reasons the 1997 Technical Advisory Group on Vaccine-Preventable
      Diseases recommended acceleration of rubella and congenital rubella syndrome
      (CRS) prevention efforts was the fact that the enhanced measles surveillance
      system in the Americas found that 25% of reported measles cases were laboratory
      confirmed rubella cases. Until 1997, the laboratory network primarily focused on
      measles diagnosis. Since 1999, due to the accelerated rubella control and CRS
      prevention strategy, laboratories have supported the regional measles, rubella,
      and CRS elimination goals. The measles-rubella laboratory network established in
      the Americas provides timely confirmation or rejection of suspected measles and
      rubella cases, and determination of the genotypic characteristics of circulating
      virus strains, critical information for the programs. A quality assurance process
      has ensured high-quality performance of procedures in the network. Challenges are
      occurring, but the measles-rubella laboratory network continues to adapt as the
      requirements of the program change, demonstrating the high quality of the
      laboratories in support of public health activities and elimination goals.

PMID- 21954263
TI  - Rubella diagnostic issues in Canada.
AB  - With the success of the rubella vaccination program, a goal for the elimination
      of rubella and congenital rubella syndrome (CRS) by 2010 has been established. To
      monitor the progress toward elimination, surveillance is critical. The laboratory
      plays an important role in both diagnostics and surveillance for rubella and CRS.
      In the elimination phase, there are particular issues and challenges that are
      important to consider when undertaking rubella diagnostics and surveillance
      activities. Although immunoglobulin (Ig) M serological testing is the primary
      diagnostic test used to confirm acute rubella infection, additional tests, such
      as paired IgG serological testing, molecular detection of rubella virus, and
      rubella IgG avidity testing need to be considered for confirming cases, depending
      on the clinical and epidemiologic context of a particular suspected rubella case.

PMID- 21954264
TI  - Serologic status of women in an urban population in Brazil before and after
      rubella immunization campaign using routine screening data.
AB  - BACKGROUND: Serologic immunity studies are necessary to evaluate immunization
      policies for rubella control and prevention of congenital rubella syndrome (CRS),
      and serologic data from regular testing for clinical follow-up can be used to
      complement surveillance information. METHODS: To assess immunity to rubella after
      an immunization campaign in 12-29-year-old girls and women, we retrospectively
      reviewed immunoglobulin (Ig) G tests performed from 2000 to 2003 in 9610 serum
      samples from pregnant subjects in Niteroi, Rio de Janeiro, Brazil. Serologic
      tests for rubella were performed using commercial enzyme immunoassays. RESULTS:
      Rubella IgG were positive in 83.9% of serum samples collected before the campaign
      and in 92.5% after the campaign. The proportion of seropositive subjects was
      inversely related to age (P < .001). The proportion of immune girls or women aged
      12-29 years, targeted by the campaign, was significantly increased after the
      campaign, whereas women aged >= 30 years, not targeted by the campaign, had no
      change in serologic immunity. Geometric mean titers for rubella IgG were
      significantly higher among pregnant girls and women after the vaccination
      campaign. CONCLUSIONS: The convenience sample provided evidence of increased
      population immunity among the girls and women targeted by the campaign, but with
      a coverage of only 83% there remains a significant population at risk for rubella
      and thus congenital rubella syndrome.

PMID- 21954265
TI  - Rubella outbreaks following virus importations: the experience of Chile.
AB  - BACKGROUND: Strategies for accelerated control of rubella and congenital rubella
      syndrome (CRS) in Chile included mass vaccination of women of childbearing age in
      1999 but did not include vaccination of adult men. METHODS: We reviewed data from
      Chile's integrated surveillance system for measles, rubella, and CRS from 2004
      through 2009 and describe the epidemiology of rubella outbreaks and
      implementation of control measures in 2005 and 2007 following mass vaccination of
      women. Population estimates from census data were used to calculate rubella
      incidence rates. The age distribution of rubella cases during 2007 was compared
      with rubella vaccination opportunities by birth cohort to orient mass vaccination
      of adult men. RESULTS: In 2005, an institutional outbreak of rubella occurred
      among male naval recruits 18-22 years of age, with 46 confirmed cases over a 5
      month period. Beginning in March 2007, rubella outbreaks among young adults in
      the capital of Santiago spread throughout Chile, resulting in >4000 confirmed
      rubella cases. Delayed control measures and rapid dissemination among young
      adults led to widespread transmission. From 2007 through 2009, rubella incidence
      was highest among adult men not included in previous vaccination strategies. Mass
      vaccination of men 19-29 years of age was conducted in November 2007 to interrupt
      rubella transmission. CONCLUSIONS: Chile's experience suggests that vaccination
      strategies for rubella and CRS elimination need to include both men and women.

PMID- 21954266
TI  - Measles outbreak in Venezuela: a new challenge to postelimination surveillance
      and control?
AB  - The circulation of wild measles virus was interrupted in Venezuela in February
      2007 after the catch-up vaccination (1994) and monitoring (1998) and in response
      to the measles outbreak in 2001. Traditionally, the routine coverage with measles
      mumps-rubella vaccine does not exceed 85%. In February 2006, a measles outbreak
      started by importation in the State Miranda; this extended to 7 states and lasted
      50 weeks with an intermediate period of 17 weeks without reported cases. New
      cases were reported in the States Guarico and Amazon. The pattern of circulation
      of the silent period was determined through the use of retrospective search for
      measles; this showed that 57% of suspected cases did not enter the surveillance
      system. Molecular epidemiology made it possible to identify B3 as only genotype,
      which also circulated in Spain. The epidemiological and clinical characteristics
      of measles have been modified; these determine outbreaks identified late, of slow
      expansion, silent, and with limited case-fatality, compared with classical
      outbreaks. The outbreak spread by that behavior was not recognized and the
      classical control measures did not result. The beginning of a broader and intense
      vaccination was delayed, partly by weaknesses in the sensitivity of the system.
      It is crucial to recognize the new behavior of measles and the effectiveness of
      the classical control measures, and especially to establish criteria for
      interruption of the circulation to control an outbreak in this stage of
      elimination.

PMID- 21954267
TI  - Guidelines for the documentation and verification of measles, rubella, and
      congenital rubella syndrome elimination in the region of the Americas.
AB  - In the region of the Americas, goals for the elimination of endemic measles and
      rubella/congenital rubella syndrome (CRS) by the year 2000 and 2010, respectively
      were established. The successful implementation of measles elimination strategies
      in the region of the Americas resulted in the interruption of endemic measles
      transmission in 2002 and tremendous progress toward rubella and CRS elimination.
      In October 2007, the 27th Pan American Sanitary Conference adopted Resolution
      CSP27.R2 urging member states to begin documenting and verifying the interruption
      of endemic transmission of the measles and rubella viruses in the Americas. To
      ensure a standardized approach for the process of documentation and verification,
      the Pan American Health Organization/World Health Organization (PAHO/WHO)
      developed a regional plan of action to guide countries and their national
      commissions as they prepare and consolidate evidence of the interruption of
      endemic measles and rubella transmission. This article summarizes the plan of
      action including the essential criteria and components of the guidelines.

PMID- 21954268
TI  - Approach to verify the status of measles, rubella, and congenital rubella
      syndrome elimination in Costa Rica.
AB  - Costa Rica introduced the measles-mumps-rubella (MMR) vaccine in 1986. The
      Ministry of Health adopted the goal of eliminating endemic measles in 1991 by
      achieving and maintaining high vaccine coverage through routine delivery, mass
      campaigns and outreach activities, and the strengthening of expanded program on
      immunization (EPI) surveillance. Measles and rubella immunization strategies
      shifted susceptibility to older age groups, leading to the introduction of MMR2
      in 1992, administered at age 7 years. In 2000, the goal of accelerated rubella
      control and congenital rubella syndrome prevention was established, and a
      nationwide vaccination campaign targeting men and women aged 15-39 was
      implemented to immunize the population of reproductive age. The last endemic case
      of measles was confirmed in 1999, and at the end of 2001 Costa Rica reported the
      last endemic cases of rubella and congenital rubella syndrome. Imported cases of
      measles and rubella were detected in 2003 and 2005, with no secondary cases
      detected. In 2008, Costa Rica established a National Committee of Experts,
      supported by technical teams, to collect the evidence required to verify the
      interruption of endemic transmission of the measles and rubella viruses. The
      evidence includes information on trends and epidemiologic analysis, molecular
      epidemiology, population immunity, the quality of surveillance, and the
      sustainability of the EPI program.

PMID- 21954269
TI  - The use of rapid coverage monitoring in the national rubella vaccination
      campaign, Haiti 2007-2008.
AB  - BACKGROUND: Prior to introduction of rubella vaccine in Haiti's national
      immunization program, the Haitian government conducted a nationwide rubella
      measles immunization campaign targeting persons 1-19 years of age to accelerate
      elimination of rubella and congenital rubella syndrome, while strengthening
      measles elimination. The national immunization campaign was conducted in phases
      by geographic region and combined multiple interventions to reach high coverage
      in all districts. METHODS: We analyzed reported data on number of doses
      administered and results of rapid monitoring by "commune" (district) to evaluate
      coverage for each vaccine and intervention in target populations. We reviewed
      measles and rubella surveillance data from Haiti's national surveillance system.
      RESULTS: Immunization registers recorded 4.7 million doses of measles-rubella
      (MR) vaccine administered to persons 1-19 years of age, reaching 80.2% of the
      estimated population of 1-4 year-olds and surpassing the target among 5-19 year
      olds. In addition, 1 million children under 5 years of age received oral polio
      vaccine and vitamin A supplements, 1.5 million school children received deworming
      treatment nationwide, and over 500000 women 15-49 years old in 2 major population
      centers received diphtheria-tetanus vaccine. Based on administrative data, 102
      (76.7%) of 133 communes attained 95% or greater coverage with MR vaccine among
      persons 1-19 years of age. Rapid monitoring in 118 communes indicated that
      coverage targets were reached in 52.5%. From 2007 to 2010, no confirmed cases of
      measles or rubella were reported from Haiti. CONCLUSIONS: The experience in Haiti
      suggests that rubella and congenital rubella syndrome can be eliminated through
      mass vaccination in countries with weak national immunization programs. However,
      high routine immunization coverage and improved surveillance are urgently needed
      to maintain measles and rubella elimination.

PMID- 21954270
TI  - Congenital rubella syndrome surveillance as a platform for surveillance of other
      congenital infections, Peru, 2004-2007.
AB  - BACKGROUND: Rubella during pregnancy can cause serious fetal abnormalities and
      death. Peru has had integrated measles/rubella surveillance since 2000 but did
      not implement congenital rubella syndrome (CRS) surveillance until 2004, in
      accordance with the Pan American Health Organization recommendations for rubella
      elimination. The article describes the experience from the CRS sentinel
      surveillance system in Peru. METHODS: Peru has maintained a national sentinel
      surveillance system for reporting confirmed and suspected CRS cases since 2004. A
      surveillance protocol was implemented with standardized case definitions and
      instruments in the selected sentinel sites. Each sentinel site completes their
      case investigations and report forms and sends the reports to the Health Region
      Epidemiology Department, which forwards the data to the national Epidemiology
      Department. CRS surveillance data were analyzed for the period 2004-2007.
      RESULTS: During the period 2004-2007, 16 health facilities, which are located in
      9 of the 33 health regions, representing the 3 main geographical areas (coast,
      mountain, and jungle), were included as sentinel sites for the CRS surveillance.
      A total of 2061 suspected CRS cases were reported to the system. Of these, 11
      were classified as CRS and 23 as congenital rubella infection. Factors
      significantly associated with rubella vertical transmission were: (1) in the
      mother, maternal history of rash during pregnancy (odds ratio [OR], 12.0; 95%
      confidence interval [CI], 3.8-37.8); (2) and in the infant, pigmentary
      retinopathy (OR, 18.4; 95% CI, 3.2-104.6), purpura (OR, 14.7; 95% CI, 2.8-78.3),
      and developmental delay (OR, 4.4; 95% CI, 1.75-11.1). CONCLUSIONS: The
      surveillance system has been able to identify rubella vertical transmission,
      reinforcing the evidence that rubella was a public health problem in Peru. This
      system may serve as a platform to implement surveillance for other congenital
      infections in Peru.

PMID- 21954271
TI  - Rubella vaccination of unknowingly pregnant women during mass campaigns for
      rubella and congenital rubella syndrome elimination, the Americas 2001-2008.
AB  - BACKGROUND: Due to the significant teratogenicity of rubella virus and the use of
      a live-attentuated vaccine, pregnancy is a contraindication of receipt of rubella
      vaccine (RCV). Data collected from several countries that have observed
      susceptible women who had received RCV during pregnancy documented that no infant
      with congenital rubella syndrome (CRS) has been born, so the risk is theoretical.
      As part of the regional initiative to eliminate rubella and CRS in the Americas,
      one of the key strategies was the vaccination of women of childbearing age. The
      implementation of mass vaccination campaigns targeting women of childbearing age
      in Argentina, Brazil, Costa Rica, Ecuador, El Salvador, and Paraguay provided an
      opportunity to further increase the body of knowledge on the safety of rubella
      vaccine if an unknowingly pregnant woman is vaccinated in early pregnancy.
      METHODS: Using a standard protocol, women who were unknowingly pregnant or become
      pregnant <= 30 days after receiving RCV were evaluated to determine immunity
      status (eg, susceptible, immune, and unknown) at the time of vaccination.
      Susceptible pregnant women were observed to determine the outcome of the
      pregnancy. For pregnancies that resulted in live births, serum samples were
      obtained from the newborn for rubella immunoglobulin (Ig) M antibody testing. If
      the newborn's serum sample was IgM positive, the infant was evaluated for
      manifestations of CRS. RESULTS: During the period 2001-2008, 48748253 women of
      childbearing age were vaccinated in the region of the Americas, 39542253 (81%) of
      whom were vaccinated in the 6 selected countries. Of these women, 30139 (0.07%)
      were pregnant or became pregnant <=1 month after receiving vaccine and were
      followed up. On the basis of serological evaluation, 2894 (10%) women were
      classified as susceptible at the time of vaccination; of their pregnancies, 1980
      (90%) resulted in a live birth. Sera from 70 (3.5%) of these infants were rubella
      IgM antibody positive, but none of the infants had features of CRS as a result of
      rubella vaccination. The maximum theoretical risk for CRS following rubella
      vaccination of susceptible pregnant women was 0.2%. Conclusions. The results of
      these studies from 6 select countries provides additional evidence showing an
      absence of risk of CRS associated with administering rubella vaccine shortly
      before or during pregnancy.

PMID- 21954272
TI  - Putting safety first: ensuring safe vaccination practices during the 2006 rubella
      campaign in Bolivia.
AB  - Over 3 weeks in 2006, 3826083 persons were vaccinated against rubella during a
      national immunization campaign in Bolivia. This campaign was the largest mass
      immunization campaign ever conducted in the country. Therefore, in addition to
      strategic and micro-planning and financial and social mobilization, issues of
      safety (eg, safe injection practices and waste management) were at the forefront
      of campaign preparations. Waste management practices were promoted through
      guidelines, training, and implementation of locally appropriate solutions. These
      experiences show that, with detailed planning and preparation, in addition to
      collaboration among key partners, effective management of waste during campaigns
      in low-income countries is both feasible and beneficial. However, challenges
      remain in implementing environmentally appropriate solutions. This campaign
      served as the launching pad for a focus on ensuring that proper waste management
      practices are used both in the routine immunization program and in subsequent
      campaigns across Bolivia.

PMID- 21954273
TI  - Pregnancy outcomes following rubella vaccination: a prospective study in the
      state of Rio de Janeiro, Brazil, 2001-2002.
AB  - BACKGROUND: A rubella mass vaccination campaign targeting 15-29-year-old women
      was performed in Brazil in 2001-2002. Rubella vaccination was contraindicated
      during pregnancy. A follow-up protocol was implemented for pregnant women who
      were vaccinated as well as their newborns. The risks of congenital rubella
      syndrome (CRS) and congenital rubella infection (CRI) after vaccination were
      assessed according to the pregnant women's immune status. METHODS: This was a
      prospective, noncontrolled study of pregnancy outcomes in women vaccinated
      against rubella in the state of Rio de Janeiro, including clinical and laboratory
      evaluations. RESULTS: Of 2292 reported pregnant women who were vaccinated, 1636
      had known outcomes: there were 1577 newborns (96.4%), 52 miscarriages (3.2%), and
      7 stillbirths (0.4%). Gestational age at vaccination was <= 5 weeks in 75% of the
      susceptible, vaccinated pregnant women. Nine newborns were positive for
      immunoglobulin M; 4 were born to susceptible pregnant women, for a 2.0% CRI rate
      (95% confidence interval, .5%-4.9%); 4 were born to vaccinated pregnant women
      with indeterminate or unknown status; and 1 had CRS, with a wild-type virus
      infection. CONCLUSIONS: The absence of vaccine-related CRS cases further supports
      recommendations to not interrupt a pregnancy exposed to rubella vaccine virus.
      Monitoring pregnancy outcomes and CRI with vaccine virus can distinguish between
      wild-type and vaccine virus infections, especially in situations of viral
      circulation.

PMID- 21954274
TI  - Follow-up study of unknowingly pregnant women vaccinated against rubella in
      Brazil, 2001-2002.
AB  - BACKGROUND: Brazil conducted mass immunization of women of childbearing age in
      2001 and 2002. Surveillance was initiated for vaccination of women during
      pregnancy to monitor the effects of rubella vaccination on fetal outcomes.
      METHODS: Women vaccinated while pregnant or prior to conception were reported to
      the surveillance system. Susceptibility to rubella infection was determined by
      anti-rubella immunoglobulin (Ig) M and IgG immunoassays. Susceptible women were
      observed through delivery. Live-born infants were tested for anti-rubella IgM
      antibody; IgM-seropositive newborns were tested for viral shedding and observed
      for 12 months for signs of congenital rubella syndrome. Incidence of congenital
      rubella infection was calculated using data from 7 states. RESULTS: A total of 22
      708 cases of rubella vaccination during pregnancy or prior to conception were
      reported nationwide, 20,536 (90%) of which were from 7 of 27 states in Brazil. Of
      these, 2332 women were susceptible to rubella infection at vaccination. Sixty
      seven (4.1%) of 1647 newborns had rubella IgM antibody (incidence rate, 4.1
      congenital infections per 100 susceptible women vaccinated during pregnancy [95%
      confidence interval, 3.2-5.1]). None of the infants infected with rubella vaccine
      virus was born with congenital rubella syndrome. CONCLUSIONS: As rubella
      elimination goals are adopted worldwide, evidence of rubella vaccine safety aids
      in planning and implementation of mass adult immunization.

PMID- 21954276
TI  - Rubella vaccination of unknowingly pregnant women during 2006 mass campaign in
      Argentina.
AB  - We report a prospective study of 56 pregnant women inadvertently vaccinated with
      rubella vaccine during the 2006 campaign performed in Argentina. Of these
      patients, 48 (87%) were immune, whereas the remaining 9 (16%) were susceptible.
      In the latter group, 7 presented with a primary reaction to the vaccine confirmed
      through immunoglobulin (Ig) G antibody avidity testing or seroconversion of IgG
      titers. During the clinical and laboratory follow-up, newborns did not present
      evidence of infection or malformations compatible with congenital rubella
      syndrome.

PMID- 21954277
TI  - Measles elimination in the Americas: a comparison between countries with a one
      dose and two-dose routine vaccination schedule.
AB  - BACKGROUND: The Region of the Americas eliminated measles in 2002 through high
      first-dose routine measles vaccine coverage and vaccination campaigns every 4-6
      years; a second routine dose at school entry was added in some countries. The
      impact of this second routine dose on measles elimination was evaluated. METHODS:
      Data on socioeconomic factors, demographic characteristics, vaccination coverage,
      and the estimated proportion of children (<15 years of age) susceptible to
      measles were compiled. Countries were grouped using propensity score methods, and
      Kaplan-Meier curves were used to compare time to measles elimination between
      countries with a 1-dose schedule and those with a 2-dose schedule. RESULTS: One
      dose (n = 14) and 2-dose (n = 7) countries did not differ with respect to median
      routine first-dose measles vaccine coverage, median coverage for 3 measles
      campaigns, or estimated percentage of susceptible children after routine first
      vaccination dose and campaigns. Compared with 1-dose countries, 2-dose countries
      had higher median gross national income per capita (P = .002), percentage of
      population living in urban areas (P = .04), and female literacy (P = .01), as
      well as lower infant mortality (P = .007); however, no differences in time to
      elimination were found. CONCLUSIONS: One-dose and 2-dose countries had similar
      times to measles elimination despite socioeconomic differences between their
      populations. A second routine dose might not have hastened measles elimination,
      because threshold immunity needed to eliminate measles was achieved with high
      first routine dose coverage and vaccination campaigns. Further research will be
      needed to determine the applicability of these findings to other regions.

PMID- 21954275
TI  - Rubella vaccination of unknowingly pregnant women: the Sao Paulo experience,
      2001.
AB  - BACKGROUND: Rubella vaccination is contraindicated during pregnancy. During mass
      immunization of women of childbearing age against rubella, women unknowingly
      pregnant may be vaccinated. To evaluate the effects of rubella vaccination during
      pregnancy, the Brazilian state of Sao Paulo conducted a follow-up study of
      pregnant women vaccinated during a rubella campaign in 2001. METHODS: Women
      vaccinated during pregnancy were reported to a national surveillance system. In
      the state of Sao Paulo, follow-up of vaccinated women included household
      interviews. Serum samples from vaccinated women were tested for antirubella
      antibodies to classify susceptibility to rubella infection. Children born to
      susceptible mothers were tested for evidence of congenital rubella infection and
      evaluated for signs of congenital rubella syndrome. RESULTS: The Sao Paulo State
      Health Department received 6473 notifications of women vaccinated during
      pregnancy. Serology performed for 5580 women identified 811 (15%) that were
      previously susceptible. Incidence of spontaneous abortion or stillbirth among
      previously susceptible vaccinated women was similar to women with prior immunity.
      Twenty-seven (4.7%) of 580 newborns tested had evidence of congenital rubella
      infection; none had congenital rubella syndrome. CONCLUSIONS: Mass rubella
      vaccination of women of childbearing age was not associated with adverse birth
      outcomes or congenital rubella syndrome among children born to women vaccinated
      during pregnancy.

PMID- 21954278
TI  - Prevalence of bisexual behaviour among bridge population of men who have sex with
      men in China: a meta-analysis of observational studies.
AB  - OBJECTIVE: To integrate the empirical estimates of bisexual behaviour among the
      bridge population of men who have sex with men (MSM) in China and their HIV and
      syphilis prevalences stratified by sexual behaviour. METHODS: The Pubmed, Chinese
      Biomedical, Chinese National Knowledge Infrastructure, VIP, Wanfang and Google
      Scholar databases were searched to January 2011 to identify relevant articles.
      Data of eligible citations were extracted by two reviewers. All analyses were
      performed using Stata 10.0. RESULTS: Forty-nine articles (including 28 739 MSM
      subjects) met the selection criteria. Aggregated findings indicated that the
      estimated prevalence of bisexual behaviour among MSM in China is 31.2% (95% CI
      28.1% to 34.5%). HIV and syphilis prevalences were 5.4% and 11.4%, respectively,
      among MSM engaging in bisexual behaviour and 3.8% and 9.3% among MSM only having
      sex with men. HIV prevalence among MSM engaging in sex with both men and women
      was significantly higher than in those who only have sex with men (OR 1.30; 95%
      CI 1.04 to 1.62; p=0.02). CONCLUSION: There is a high prevalence of bisexual
      behaviour among MSM in China and bisexual behaviour is significantly associated
      with increased HIV infection risk. The results of this meta-analysis highlight a
      critical pattern of HIV transmission among MSM in China and indicate that
      targeted interventions aimed at encouraging safe sex practices and promoting
      societal and family acceptance of MSM are urgently needed.

PMID- 21954279
TI  - Ovarian cortex transplantation in the baboon: comparison of four different intra
      abdominal transplantation sites.
AB  - BACKGROUND: Several sites have been used for ovarian cortex transplantation (OCT)
      in humans. The present study was designed to evaluate different intra-abdominal
      transplantation sites in the baboon to gain further knowledge about alternative
      transplantation sites in a human setting. METHODS: Autologous fresh OCTs were
      performed in 12 baboons (Papio anubis). Four different sites were tested: the
      free portion of the omentum (OMF), the portion of the omentum adjacent to the
      spleen (OMS), the pouch of Douglas (D) and the pelvic wall on the psoas muscle
      (PW). Cortex survival, follicle density, cyclicity and hormonal levels were
      compared between the different sites, 3 and 6 months after transplantation.
      RESULTS: Macroscopically, antral follicles were only found in the OMS and OMF
      locations, which also showed a higher proportion of follicle-containing cortex at
      light microscopy (OMF 71.4%, OMS 83.3% versus PW 58.8% and D 40%, P< 0.05).
      Higher densities of primordial [OMF: 3.54 (0-13.18) follicles/grid, OMS: 3.85 (0
      8.53), PW: 0 (0-13.25), D 0 (0-1.33), P< 0.05] and primary follicles [OMF: 3.54
      (0-18.52), OMS: 3.85 (0-1), PW: 0 (0-4.58), D 0 (0-0.25), P< 0.05] was also found
      in the omental locations. CONCLUSIONS: Omental locations provide a better site,
      in terms of follicle survival, for intra-abdominal OCT in the baboon compared
      with the pelvic wall and the D.

PMID- 21954280
TI  - Predictive factors of ovarian response and clinical outcome after IVF/ICSI
      following a rFSH/GnRH antagonist protocol with or without oral contraceptive pre
      treatment.
AB  - BACKGROUND: Prediction of ovarian response prior to the first controlled ovarian
      stimulation (COS) cycle is useful in determining the optimal starting dose of
      recombinant FSH (rFSH). However, potentially predictive factors may be subject to
      inter-cycle variability and many patients are pre-treated with oral
      contraceptives (OC) for scheduling purposes. Our objective was to determine
      predictive factors of ovarian response for patients undergoing COS with rFSH in a
      gonadotrophin-releasing hormone antagonist protocol and to determine the inter
      cycle variability of these factors. METHODS: In this multinational trial, 442
      patients were randomized to receive either OC treatment or no treatment prior to
      their first COS cycle. For candidate predictive factors, patient characteristics
      were collected at screening, and endocrine and sonographic data were collected
      during the early follicular phase of the two subsequent cycles. A treatment
      regimen of 200 IU rFSH and 0.25 mg ganirelix was applied during the second cycle.
      Predictive factors of ovarian response and of too low (<6 oocytes) or too high
      (>18 oocytes) ovarian responses were determined using stepwise linear regression
      and stepwise logistic regression, respectively. RESULTS: Anti-Mullerian hormone
      (AMH) and basal FSH were statistically significant predictors of the number of
      oocytes retrieved and of an excessive ovarian response. For low ovarian response,
      AMH was the only significant predictive factor. In the non-OC group, the
      predictive value was higher than in the OC group and higher at the early
      follicular phase of the stimulation cycle than of the previous cycle. The inter
      cycle variation for AMH was low compared with the inter-cycle variation of other
      hormones. Between the two groups, there were no differences in the number or
      quality of embryos obtained or transferred, but the implantation rate was
      significantly lower in the OC group (24.1 versus 30.1%, P= 0.03), resulting in an
      ongoing pregnancy rate of 26.3% compared with 35.7% in the non-OC group (P=
      0.05). CONCLUSIONS: The best predictive model of ovarian response was in the non
      OC group and included both AMH and basal FSH determined at the early follicular
      phase of the stimulation cycle. In the proceeding cycle, AMH alone had sufficient
      predictive value since it was not affected by inter-cycle variability or OC
      pretreatment.

PMID- 21954281
TI  - The prevalence and impact of fibroids and their treatment on the outcome of
      pregnancy in women with recurrent miscarriage.
AB  - BACKGROUND: Although uterine fibroids have been associated with spontaneous
      miscarriage, to our knowledge there have been no studies in the literature
      assessing their role in the recurrent miscarriage (RM) population. The aims of
      this study are to examine the impact of different types of fibroids on the
      pregnancy outcome of women with RM and to investigate to what extent resection of
      fibroids distorting the uterine cavity affects the outcome of a future pregnancy.
      METHODS: The study analysed retrospective and prospective data from a large
      tertiary referral RM clinic. Couples were investigated as per an established
      protocol. Fibroids were diagnosed using combined transvaginal ultrasound and
      hysterosalpingography. Fibroids distorting the uterine cavity were resected via
      hysteroscopy. Two study groups were subsequently examined: women with cavity
      distorting fibroids who underwent surgery (n =25) and women with fibroids not
      distorting the cavity who did not undergo any intervention (n =54). The latter
      was compared with a control group of women with unexplained RM (n =285). RESULTS:
      The prevalence of fibroids was found to be 8.2% (79/966). In total, 264
      pregnancies of women with fibroids and 936 pregnancies of women with unexplained
      RM were analysed. Women with intracavitary distortion and undergoing myomectomy
      significantly reduced their mid-trimester miscarriage rates in subsequent
      pregnancies from 21.7 to 0% (P< 0.01). This translated to an increase in the live
      birth rate from 23.3 to 52.0% (P< 0.05). Women with fibroids not distorting the
      cavity behaved similarly to women with unexplained RM achieving a 70.4% live
      birth rate in their subsequent pregnancies without any intervention. CONCLUSIONS:
      Fibroids are associated with increased mid-trimester losses amongst women with
      RM. Resection of fibroids distorting the uterine cavity can eliminate the mid
      trimester losses and double the live birth rate in subsequent pregnancies. Women
      with fibroids not distorting the uterine cavity can achieve high live birth rates
      without intervention.

PMID- 21954282
TI  - Healthcare accreditation systems: further perspectives on performance measures.
AB  - OBJECTIVE: The purpose of this paper is to identify and suggest a number of
      performance measures to facilitate the evaluation of accreditation programs in
      healthcare. METHODS: The paper is based on an exploratory research which has used
      qualitative methods, including snowball sampling technique, email interview and
      thematic content analysis. PARTICIPANTS: Respondents (experts and professionals)
      were selected from a diverse spectrum ranging from healthcare organizations,
      universities and accreditation-associated institutions. RESULTS: The analysis of
      the data provided key measures to be considered in the evaluation of
      accreditation programs' impact at macro and micro levels as well as their nature
      and operations. The measures can be used to, for example, assess the degree of
      stakeholders' reliance on accreditation results, measure the cost of
      accreditation for participating organizations and serve as a formal mechanism for
      accredited organizations to appeal accreditation decisions. CONCLUSIONS: This
      paper has brought together a number of generic, yet influential and workable,
      measures which could be utilized for assessing the overall performance of an
      accreditation program in healthcare. The application of these measures depends on
      the features of given accreditation program and the context in which the program
      operates. Therefore, the next step/steps in the assessment of an accreditation
      program might be choosing the measures suiting that program.

PMID- 21954283
TI  - The multiple roles of the CD8 coreceptor in T cell biology: opportunities for the
      selective modulation of self-reactive cytotoxic T cells.
AB  - Short peptide fragments generated by intracellular protein cleavage are presented
      on the surface of most nucleated cells bound to highly polymorphic MHCI
      molecules. These pMHCI complexes constitute an interface that allows the immune
      system to identify and eradicate anomalous cells, such as those that harbor
      infectious agents, through the activation of CTLs. Molecular recognition of pMHCI
      complexes is mediated primarily by clonally distributed TCRs expressed on the
      surface of CTLs. The coreceptor CD8 contributes to this antigen-recognition
      process by binding to a largely invariant region of the MHCI molecule and by
      promoting intracellular signaling, the effects of which serve to enhance TCR
      stimuli triggered by cognate ligands. Recent investigations have shed light on
      the role of CD8 in the activation of MHCI-restricted, antigen-experienced T cells
      and in the processes of T cell selection and lineage commitment in the thymus.
      Here, we review these data and discuss their implications for the development of
      potential therapeutic strategies that selectively target pathogenic CTL responses
      erroneously directed against self-derived antigens.

PMID- 21954284
TI  - Characterization of the nature of granulocytic myeloid-derived suppressor cells
      in tumor-bearing mice.
AB  - MDSCs are a group of cells with potent immune-suppressive activity. These cells
      accumulate in many pathologic conditions and play a major role in the regulation
      of immune responses. The nature of MDSC remains highly debatable. In cancer, most
      MDSCs are represented by cells with granulocytic phenotype and morphology, G
      MDSC. The relationship between G-MDSCs and Neu remains unclear. In this study, we
      have found that G-MDSCs, from tumor-bearing, and Neu, from tumor-free, mice share
      a common morphology and phenotype. However, in contrast to Neu, a substantial
      proportion of G-MDSCs expressed M-CSFR and a CD244 molecule. Neu had
      significantly higher phagocytic activity, expression of lysosomal proteins, and
      TNF-alpha than corresponding G-MDSCs, which had significantly higher activity of
      arginase, MPO, and ROS. In contrast to G-MDSC, neither rested nor mobilized Neu
      suppressed T cells. G-MDSC survived 2 days in culture in the presence of GM-CSF
      and within 24 h, became phenotypic and functionally similar to Neu. Tumor
      associated G-MDSC shared most characteristics of splenic G-MDSC, rather then Neu.
      These data suggest that in cancer, despite morphological and phenotypic
      similarities, G-MDSCs are functionally distinct from Neu and are comprised of
      pathologically activated precursors of Neu.

PMID- 21954285
TI  - alpha-Tocopherol induces hematopoietic stem/progenitor cell expansion and ERK1/2
      mediated differentiation.
AB  - Tocopherols promote or inhibit growth in different cell types. In the
      hematopoietic system, the radioprotective property of tocopherols is thought to
      act through the expansion of primitive hematopoietic cells. However, the
      mechanisms activated by tocopherols and which HPs are affected remain poorly
      understood. To better address these questions, mice were treated with alpha
      tocopherol, and its effects were investigated in the BM microenvironment. alpha
      Tocopherol induced increased proliferation in HSC/HP cells, leading to BM
      hyperplasia. In addition, differentiation to the granulocytic/monocytic lineage
      was enhanced by alpha-tocopherol treatment. alpha-Tocopherol treatment resulted
      in decreased basal phosphorylation of ERK1/2, PKC, and STAT-5 in HSC/HP cells. In
      contrast, alpha-tocopherol enhanced ERK1/2 activation in response to IL-3
      stimulation in HSC/HP cells without altering the expression of IL-3Rs. Moreover,
      alpha-tocopherol-induced differentiation and ERK1/2 activation were abolished in
      mice pretreated with a MEK inhibitor (PD98059); however, pretreatment with
      PD98059 did not reduce the alpha-tocopherol-mediated increase in HSC/HP cells but
      instead, further enhanced their proliferation. Therefore, alpha-tocopherol
      induces expansion of HSC/HP cells by a nonidentified intracellular pathway and
      granulocytic/monocytic differentiation through ERK1/2 activation.

PMID- 21954286
TI  - Stable accumulation of p67phox at the phagosomal membrane and ROS production
      within the phagosome.
AB  - Production of ROS by the leukocyte NADPH oxidase is essential for the destruction
      of pathogenic bacteria inside phagosomes. The enzyme is a complex of cytosolic
      and membranous subunits that need to assemble upon activation. Biochemical data
      suggest that the complex is renewed continuously during activity. Furthermore, it
      is generally assumed that complex assembly and activity occur in parallel.
      However, information about the oxidase assembly in individual phagosomes in live
      cells is scarce. We studied the dynamic behavior of the crucial cytosolic NADPH
      oxidase component p67(phox) during phagocytosis by videomicroscopy. p67(phox) is
      involved in the regulation of electron flow from NADPH to oxygen, leading to
      superoxide radical formation inside the phagosome. p67(phox)-citrine, expressed
      in myeloid PLB-985 cells, accumulated at the phagosomal membrane during
      phagocytosis of yeast particles. Using photobleaching techniques (FRAP, FLIP), we
      demonstrated that p67(phox)-citrine diffused freely in this phagosomal membrane,
      but the phagosomal pool of p67(phox)-citrine did not exchange with the cytosolic
      pool. This result suggests that once assembled in the NADPH oxidase complex,
      p67(phox) is stable in this complex. Furthermore, the time of the presence of
      p67(phox)-citrine at the phagosome increased substantially in the presence of
      complement in the opsonizing serum compared with decomplemented serum. PI(3)P
      also accumulated around phagosomes for twice as long in the presence of
      complement. The presence of p67(phox)-citrine was correlated with the duration of
      phagosomal ROS production in different opsonization conditions. These data
      support the critical role of p67(phox) for ROS production on the level of
      individual phagosomes.

PMID- 21954287
TI  - Phenotypic spectrum associated with CASK loss-of-function mutations.
AB  - BACKGROUND: Heterozygous mutations in the CASK gene in Xp11.4 have been shown to
      be associated with a distinct brain malformation phenotype in females, including
      disproportionate pontine and cerebellar hypoplasia. METHODS: The study
      characterised the CASK alteration in 20 new female patients by molecular
      karyotyping, fluorescence in situ hybridisation, sequencing, reverse
      transcriptase (RT) and/or quantitative real-time PCR. Clinical and brain imaging
      data of a total of 25 patients were reviewed. RESULTS: 11 submicroscopic copy
      number alterations, including nine deletions of ~11 kb to 4.5 Mb and two
      duplications, all covering (part of) CASK, four splice, four nonsense, and one 1
      bp deletion are reported. These heterozygous CASK mutations most likely lead to a
      null allele. Brain imaging consistently showed diffuse brainstem and cerebellar
      hypoplasia with a dilated fourth ventricle, but of remarkably varying degrees.
      Analysis of 20 patients in this study, and five previously reported patients,
      revealed a core clinical phenotype comprising severe developmental
      delay/intellectual disability, severe postnatal microcephaly, often associated
      with growth retardation, (axial) hypotonia with or without hypertonia of
      extremities, optic nerve hypoplasia, and/or other eye abnormalities. A
      recognisable facial phenotype emerged, including prominent and broad nasal bridge
      and tip, small or short nose, long philtrum, small chin, and/or large ears.
      CONCLUSIONS: These findings define the phenotypic spectrum associated with CASK
      loss-of-function mutations. The combination of developmental and brain imaging
      features together with mild facial dysmorphism is highly suggestive of this
      disorder and should prompt subsequent testing of the CASK gene.

PMID- 21954288
TI  - Akt determines cell fate through inhibition of the PERK-eIF2alpha phosphorylation
      pathway.
AB  - Metazoans respond to various forms of environmental stress by inducing the
      phosphorylation of the alpha subunit of eukaryotic translation initiation factor
      2 (eIF2alpha) at serine-51, a modification that leads to global inhibition of
      mRNA translation. We demonstrate induction of the phosphorylation of eIF2alpha in
      mammalian cells after either pharmacological inhibition of the phosphoinositide 3
      kinase (PI3K)-Akt pathway or genetic or small interfering RNA-mediated ablation
      of Akt. This increase in the extent of eIF2alpha phosphorylation also occurred in
      Drosophila cells and depended on the endoplasmic reticulum (ER)-resident protein
      kinase PERK, which was inhibited by Akt-dependent phosphorylation at threonine
      799. The activity of PERK and the abundance of phosphorylated eIF2alpha
      (eIF2alphaP) were reduced in mouse mammary gland tumors that contained activated
      Akt, as well as in cells exposed to ER stress or oxidative stress. In unstressed
      cells, the PERK-eIF2alphaP pathway mediated survival and facilitated adaptation
      to the deleterious effects of the inactivation of PI3K or Akt. Inactivation of
      the PERK-eIF2alphaP pathway increased the susceptibility of tumor cells to death
      by pharmacological inhibitors of PI3K or Akt. Thus, we suggest that the PERK
      eIF2alphaP pathway provides a link between Akt signaling and translational
      control, which has implications for tumor formation and treatment.

PMID- 21954289
TI  - Time-dependent quantitative multicomponent control of the G1-S network by the
      stress-activated protein kinase Hog1 upon osmostress.
AB  - Control of cell cycle progression by stress-activated protein kinases (SAPKs) is
      essential for cell adaptation to extracellular stimuli. Exposure of yeast to
      hyperosmotic stress activates the SAPK Hog1, which delays cell cycle progression
      through G1 by direct phosphorylation of the cyclin-dependent kinase (CDK)
      inhibitor Sic1 and by inhibition of the transcription of the genes encoding the
      G1 cyclins Cln1 and 2. Additional targets of Hog1 may also play a role in this
      response. We used mathematical modeling and quantitative in vivo experiments to
      define the contributions of individual components of the G1-S network downstream
      of Hog1 to this stress-induced delay in the cell cycle. The length of the arrest
      depended on the degree of stress and the temporal proximity of the onset of the
      stress to the commitment to cell division, called "Start." Hog1-induced
      inhibition of the transcription of the gene encoding cyclin Clb5, rather than
      that of the gene encoding Cln2, prevented entry into S phase upon osmostress. By
      controlling the accumulation of specific cyclins, Hog1 delayed bud morphogenesis
      (through Clns) and delayed DNA replication (through Clb5). Hog1-mediated
      phosphorylation and degradation of Sic1 at Start prevented residual activity of
      the cyclin/CDK complex Clb5/Cdc28 from initiating DNA replication before
      adaptation to the stress. Thus, our work defines distinct temporal roles for the
      actions of Hog1 on Sic1 and cyclins in mediating G1 arrest upon hyperosmotic
      stress.

PMID- 21954290
TI  - Tyrosine phosphorylation of the Galpha-interacting protein GIV promotes
      activation of phosphoinositide 3-kinase during cell migration.
AB  - GIV (Galpha-interacting vesicle-associated protein; also known as Girdin)
      enhances Akt activation downstream of multiple growth factor- and G protein
      (heterotrimeric guanosine 5'-triphosphate-binding protein)-coupled receptors to
      trigger cell migration and cancer invasion. We demonstrate that GIV is a tyrosine
      phosphoprotein that directly binds to and activates phosphoinositide 3-kinase
      (PI3K). Upon ligand stimulation of various receptors, GIV was phosphorylated at
      tyrosine-1764 and tyrosine-1798 by both receptor and non-receptor tyrosine
      kinases. These phosphorylation events enabled direct binding of GIV to the amino-
      and carboxyl-terminal Src homology 2 domains of p85alpha, a regulatory subunit of
      PI3K; stabilized receptor association with PI3K; and enhanced PI3K activity at
      the plasma membrane to trigger cell migration. Tyrosine phosphorylation of GIV
      and its association with p85alpha increased during metastatic progression of a
      breast carcinoma. These results suggest a mechanism by which multiple receptors
      activate PI3K through tyrosine phosphorylation of GIV, thereby making the GIV
      PI3K interaction a potential therapeutic target within the PI3K-Akt pathway.

PMID- 21954291
TI  - Bistability in biochemical signaling models.
AB  - This Teaching Resource provides lecture notes, slides, and a student assignment
      for a two-part lecture on the principles underlying bistability in biochemical
      signaling networks, which are illustrated with examples from the literature. The
      lectures cover analog, or graded, versus digital, all-or-none, responses in
      cells, with examples from different types of biological processes requiring each.
      Rate-balance plots are introduced as a method for determining whether generic one
      variable systems exhibit one or several stable steady states. Bifurcation
      diagrams are presented as a more general method for detecting the presence of
      bistability in biochemical signaling networks. The examples include an artificial
      toggle switch, the lac operon in bacteria, and the mitogen-activated protein
      kinase cascade in both Xenopus oocytes and mammalian cells. The second part of
      the lecture links the concepts of bistability more closely to the mathematical
      tools provided by dynamical systems analysis. The examples from the first part of
      the lecture are analyzed with phase-plane techniques and bifurcation analysis,
      using the scientific programming language MATLAB. Using these programs as a
      template, the assignment requires the students to implement a model from the
      literature and analyze the stability of this model's steady states.

PMID- 21954292
TI  - Computational modeling of the cell cycle.
AB  - This Teaching Resource provides lecture notes, slides, and a problem set for
      introducing graduate-level students to computational biology through a simple
      mathematical model of the cell cycle. The model simulates interactions between
      cyclin B and cyclin-dependent kinase 1, proteins that together form the mitosis
      promoting factor (MPF), which initiates the processes leading to mitosis. The
      lecture begins with a biological background describing the importance of MPF for
      mitosis, the components of MPF, and the changes in cellular MPF observed during
      different phases of the cell cycle. The model is compared with newer, more
      mechanistically detailed models of the same process, which allows for a
      discussion of the insights that can be gained even from simplified models. The
      lecture concludes with a demonstration of how this model can be implemented in
      the scientific programming language MATLAB and includes a problem set.

PMID- 21954293
TI  - Developing models in virtual cell.
AB  - This Teaching Resource provides lecture notes, slides, and a student assignment
      for a two-part lecture on mathematical modeling using the Virtual Cell
      environment. The lectures discuss the steps involved in developing and running
      simulations using Virtual Cell, with particular focus on spatial partial
      differential equation models. We discuss how to construct both ordinary
      differential equation models, in which the cytoplasm is considered a well-mixed
      cellular compartment, and partial differential equation models, which calculate
      how chemical species change as a function of both time and location. The Virtual
      Cell environment is especially well suited for models that explore spatial
      specificity of cellular reactions. Partial differential equation models in
      Virtual Cell can give rise to simulations using predefined cellular geometries,
      which enable direct comparison with imaging data. These models address questions
      regarding the regulatory capability arising from spatial organization of the
      cell. Examples are provided of studies that have successfully exploited the
      Virtual Cell software to address the spatial contribution to signaling.

PMID- 21954294
TI  - Simulations of stochastic biological phenomena.
AB  - This Teaching Resource provides lecture notes, slides, and a student assignment
      for a two-part lecture that introduces stochastic modeling of biological systems.
      The first lecture uses biological examples to present the concept of cell-to-cell
      variability and makes the connection between the variability of single-cell
      measurements and concepts from statistical mechanics and probability theory. This
      section makes the point that for low copy number of a species, the usual
      differential equation formalism is no longer applicable and needs to be replaced
      by a probabilistic approach based on the so-called Master Equation. As an
      example, a simple model of gene transcription is discussed in detail, the
      different contributions to the relevant Master Equation are highlighted, and the
      equation itself is derived. The second lecture describes how, for more complex
      and biologically interesting applications, direct solution of the Master Equation
      becomes difficult. Gillespie's algorithm, which is used in most cases of
      biological interest, is then introduced as a practical alternative. The lecture
      delves into the crux of Gillespie's algorithm, which entails the drawing of two
      random numbers at each time step. It establishes the corresponding formalism,
      details the connection between chemical rate constants and Gillespie rates, and
      culminates in a description and explanation of a core MATLAB program for the
      transcriptional model considered in the first lecture. This core program, written
      for a single cell, is expanded by the students in the homework assignment to
      consider both transcription and translation.

PMID- 21954295
TI  - Probabilistic reasoning in data analysis.
AB  - This Teaching Resource provides lecture notes, slides, and a student assignment
      for a lecture on probabilistic reasoning in the analysis of biological data.
      General probabilistic frameworks are introduced, and a number of standard
      probability distributions are described using simple intuitive ideas. Particular
      attention is focused on random arrivals that are independent of prior history
      (Markovian events), with an emphasis on waiting times, Poisson processes, and
      Poisson probability distributions. The use of these various probability
      distributions is applied to biomedical problems, including several classic
      experimental studies.

PMID- 21954296
TI  - Biomedical model fitting and error analysis.
AB  - This Teaching Resource introduces students to curve fitting and error analysis;
      it is the second of two lectures on developing mathematical models of biomedical
      systems. The first focused on identifying, extracting, and converting required
      constants--such as kinetic rate constants--from experimental literature. To
      understand how such constants are determined from experimental data, this lecture
      introduces the principles and practice of fitting a mathematical model to a
      series of measurements. We emphasize using nonlinear models for fitting nonlinear
      data, avoiding problems associated with linearization schemes that can distort
      and misrepresent the data. To help ensure proper interpretation of model
      parameters estimated by inverse modeling, we describe a rigorous six-step
      process: (i) selecting an appropriate mathematical model; (ii) defining a "figure
      of-merit" function that quantifies the error between the model and data; (iii)
      adjusting model parameters to get a "best fit" to the data; (iv) examining the
      "goodness of fit" to the data; (v) determining whether a much better fit is
      possible; and (vi) evaluating the accuracy of the best-fit parameter values.
      Implementation of the computational methods is based on MATLAB, with example
      programs provided that can be modified for particular applications. The problem
      set allows students to use these programs to develop practical experience with
      the inverse-modeling process in the context of determining the rates of cell
      proliferation and death for B lymphocytes using data from BrdU-labeling
      experiments.

PMID- 21954297
TI  - Decoding natural signals from the peripheral retina.
AB  - Ganglion cells in the peripheral retina have lower density and larger receptive
      fields than in the fovea. Consequently, the visual signals relayed from the
      periphery have substantially lower resolution than those relayed by the fovea.
      The information contained in peripheral ganglion cell responses can be quantified
      by how well they predict the foveal ganglion cell responses to the same stimulus.
      We constructed a model of human ganglion cell outputs by combining existing
      measurements of the optical transfer function with the receptive field properties
      and sampling densities of midget (P) ganglion cells. We then simulated a spatial
      population of P-cell responses to image patches sampled from a large collection
      of luminance-calibrated natural images. Finally, we characterized the population
      response to each image patch, at each eccentricity, with two parameters of the
      spatial power spectrum of the responses: the average response contrast (standard
      deviation of the response patch) and the falloff in power with spatial frequency.
      The primary finding is that the optimal estimate of response contrast in the
      fovea is dependent on both the response contrast and the steepness of the falloff
      observed in the periphery. Humans could exploit this information when decoding
      peripheral signals to estimate contrasts, estimate blur levels, or select the
      most informative locations for saccadic eye movements.

PMID- 21954298
TI  - Reweighting visual cues by touch.
AB  - It is well established that if multiple cues provide information about the same
      quantity, the information from these cues is combined by weighting each cue by
      the inverse of its variance. This implies that cue weights are determined by the
      cue variances only. However, this view is challenged by studies that showed that
      feedback about the actual value can induce changes in the cue weights when the
      feedback is consistent with one cue but not the other. We developed a paradigm
      that allowed us to measure the time course of this reweighting. Subjects placed
      an object flush onto a slanted surface. Monocular and binocular cues provided
      information about the slant and could be inconsistent with one another. Subjects
      received haptic feedback about whether they had oriented the object correctly
      when the object contacted the surface. This feedback was consistent with either
      the monocular or the binocular information. We found that the weight given to the
      visual cue that was consistent with the feedback increased relatively fast,
      leading to a mean weight change of 0.18 after 52 conflict trials. Thus, unless
      the haptic feedback somehow influences the reliability of the individual visual
      cues, the cue weights are not fully determined by the cue variances but also
      depend on the accuracy of each cue.

PMID- 21954299
TI  - A dual visual-local feedback model of the vergence eye movement system.
AB  - Pure vergence movements are the eye movements that we make when we change our
      binocular fixation between targets differing in distance but not in direction
      relative to the head. Pure vergence is slow and controlled by visual feedback.
      Saccades are the rapid eye movements that we make between targets differing in
      direction. Saccades are extremely fast and controlled by a local, non-visual
      feedback loop. Usually, we change our fixation between targets that differ in
      both distance and direction. Then, vergence eye movements are combined with
      saccades. A number of models have been proposed to explain the dynamics of
      saccade-related vergence movements. The models have in common that visual input
      is ignored for the duration of the responses. This type of control is realistic
      for saccades but not for vergence. Here, I present computations performed to
      investigate if a model using dual visual and local feedback can replace the
      current models. Simulations and stability analysis lead to a model that computes
      an estimate of target vergence instead of retinal disparity and uses this signal
      as the main drive. Further analysis shows that the model describes the dynamics
      of pure vergence responses over the full physiological range, saccade-related
      vergence movements, and vergence adaptation. The structure of the model leads to
      new hypotheses about the control of vergence.

PMID- 21954300
TI  - The detection of feigned disabilities: the effectiveness of the Personality
      Assessment Inventory in a traumatized inpatient sample.
AB  - Research on feigned mental disorders indicates that severe psychopathology
      coupled with significant trauma histories often complicate feigning
      determinations, resulting in inaccuracies on otherwise effective measures. As
      part of malingering assessments, the Personality Assessment Inventory (PAI) is
      often used because of its excellent validation and the availability of three
      feigning indicators (Negative Impression, Malingering Index, and Rogers
      Discriminant Function), which have evidenced large effect sizes and clinically
      useful cut scores. The current study examined the effectiveness of the PAI in a
      traumatized inpatient sample using a between-subjects simulation design. Although
      Negative Impression appeared affected by trauma--especially in conjunction with
      dissociative symptoms--very positive results were found for Malingering Index and
      Rogers Discriminant Function. They remained relatively unelevated under honest
      conditions, despite posttraumatic stress disorder and extensive comorbidity.
      Using single-point cut scores provided moderately good classification of feigned
      and genuine PAI profiles. For purposes of classification, the authors
      operationally defined small indeterminate groups that were considered too close
      to classify (i.e., +/-5T of the cut scores). With indeterminate cases removed,
      the overall classification rates improved modestly. However, the more important
      finding involved the error rates for the indeterminate group, which exceeded 50%.
      Directions for further research are discussed.

PMID- 21954301
TI  - GABAB receptor-positive modulators: brain region-dependent effects.
AB  - This study examined the positive modulatory properties of 2,6-di-tert-butyl-4-(3
      hydroxy-2,2-dimethyl-propyl)-phenol (CGP7930) and (R,S)-5,7-di-tert-butyl-3
      hydroxy-3-trifluoromethyl-3H-benzofuran-2-one (rac-BHFF) at gamma-aminobutyric
      acid B (GABA(B)) receptors in different brain regions. Using quantitative
      autoradiography, we measured GABA(B) receptor-stimulated binding of guanosine 5'
      O-(3-[35S]thiotriphosphate) ([35S]GTPgammaS) to G proteins in medial prefrontal
      cortex (mPFC), hippocampus, and cerebellum. CGP7930 and rac-BHFF enhanced
      baclofen-stimulated [35S]GTPgammaS binding similarly in mPFC and hippocampus, but
      were more effective in cerebellum. CGP7930 (100 MUM) increased [35S]GTPgammaS
      binding stimulated by baclofen (30 MUM) from 29 to 241% above basal in mPFC and
      from 13 to 1530% above basal in cerebellum. Likewise, rac-BHFF (10 MUM) increased
      baclofen-stimulated [35S]GTPgammaS binding more in cerebellum (from 13 to 1778%
      above basal) than in mPFC (from 29 to 514% above basal). rac-BHFF (10 MUM) in
      combination with gamma-hydroxybutyrate (20 mM) increased [35S]GTPgammaS binding
      in cerebellum but not in mPFC. rac-BHFF also enhanced the effects of 3
      aminopropyl(diethoxymethyl)phosphinic acid (CGP35348). Consistent with its
      partial agonist properties, CGP35348 stimulated [35S]GTPgammaS binding in mPFC
      when given alone (to 18% above basal), but less extensively than baclofen (140%
      above basal), and antagonized baclofen when given together. CGP35348 (1 mM) in
      combination with rac-BHFF (100 MUM) produced an increase in [35S]GTPgammaS
      binding that was larger in cerebellum (from 61 to 1260% above basal) than in mPFC
      (from 18 to 118% above basal). Taken together, the results show that GABA(B)
      receptor-positive modulators enhance [35S]GTPgammaS binding stimulated by GABA(B)
      receptor agonists in a brain region-dependent manner. This regionally selective
      enhancement is further evidence of pharmacologically distinct GABA(B) receptor
      populations, possibly allowing for more selective therapeutic targeting of the
      GABA(B) system.

PMID- 21954302
TI  - Lead: ongoing public and occupational health issues in vulnerable populations: a
      case study.
AB  - BACKGROUND: Lead has been recognized increasingly as a public health risk,
      although with the introduction of wide-ranging occupational and public health
      measures, levels of blood lead in the general population of the UK and other
      developed nations have been in decline in recent years. Nonetheless, cases of
      lead poisoning still occur. METHODS: We report on a large cluster of exposed lead
      workers and their families, including several children. The focus of the
      occupational and public health investigations was to identify the different
      groups at risk and the pathways by which potential exposures were taking place.
      RESULTS: Lead in the workplace was found to account for the raised blood lead
      levels amongst the workers with exposure occurring as a result of insufficient
      demarcation between 'clean' and 'dirty' areas, and from contamination of personal
      belongings with lead. Furthermore, there was evidence of para-occupational
      exposure of family members. CONCLUSIONS: The successful control of lead in this
      case required multidisciplinary working. Efforts included extensive workplace
      controls, along with the education and care of workers and their families, though
      complicated by lack of familiarity with the UK health service amongst the
      affected groups, language barriers, underlying low levels of literacy and high
      mobility.

PMID- 21954303
TI  - Comparison of systematic developmental surveillance with standardized
      developmental screening in primary care.
AB  - Many physicians use surveillance questions to assess development; the American
      Academy of Pediatrics recommends screening at 9-, 18-, and 24-month health
      supervision visits (HSVs). There are no studies directly comparing surveillance
      with screening. The authors directly compared systematic surveillance with
      standardized screening using a cross-sectional observational study of children
      with no known delays. Surveillance questions were completed at each HSV. The Ages
      and Stages Questionnaire (ASQ) was administered following the 9-, 18-, or 24
      month HSV. The authors compared detection of delays by surveillance with ASQ
      screening. Using surveillance, 11/95 subjects were identified as delayed. Using
      the ASQ, 15/95 subjects scored fail; 28/95 scored monitor. Among the 11 delayed
      surveillance subjects, 5 scored fail on the ASQ and 5 scored monitor. Ten of the
      15 subjects scoring fail on the ASQ were not identified by surveillance. The
      study's findings support the American Academy of Pediatrics recommendations for
      periodic formal screening in addition to continued surveillance.

PMID- 21954304
TI  - Family-centered rounds: views of families, nurses, trainees, and attending
      physicians.
AB  - OBJECTIVE: To study the impact of family-centered rounds for general pediatrics
      inpatients. METHODS: An observation tool and participant surveys was developed.
      The authors analyzed rounding time and rounds participants. Associations between
      family presence and participants' satisfaction were analyzed. RESULTS: Data were
      collected on 295 patients and from 257 staff members. Average rounding time was
      reduced with increased family and nurse presence (8.7 minutes with both, 12.7
      minutes without family, P = .0001). Families reported high satisfaction
      regardless of participants. Families present on rounds reported increased
      knowledge of team members' roles (54% vs 35%, P = .04). Attending physicians more
      often reported ease in managing rounds with families present. Senior residents
      perceived decreased autonomy with high family participation (11%) versus low
      family participation (70%; P = .02). Improved nurse satisfaction was associated
      with increased family and nurse participation. CONCLUSION: Family participation
      may shorten inpatient rounds. Families and staff were satisfied with family
      centered rounds, though senior resident autonomy requires attention.

PMID- 21954305
TI  - RNA-mediated reciprocal regulation between two bacterial operons is RNase III
      dependent.
AB  - In bacteria, RNAs regulate gene expression and function via several mechanisms.
      An RNA may pair with complementary sequences in a target RNA to impact
      transcription, translation, or degradation of the target. Control of conjugation
      of pCF10, a pheromone response plasmid of Enterococcus faecalis, is a well
      characterized system that serves as a model for the regulation of gene expression
      in bacteria by intercellular signaling. The prgQ operon, whose products mediate
      conjugation, is negatively regulated by two products of the prgX operon, Anti-Q,
      a small RNA, and PrgX, the transcriptional repressor of the prgQ promoter. Here
      we show that Qs, an RNA from the 5' end of the prgQ operon, represses expression
      of PrgX by targeting prgX mRNA for cleavage by RNase III. Our results demonstrate
      that the prgQ and prgX operons each use RNAs to negatively regulate gene
      expression from the opposing operon by different mechanisms. Such reciprocal
      regulation between two operons using RNAs has not been previously demonstrated.
      Furthermore, these results show that Qs is an unusually versatile RNA, serving
      three separate functions in the regulation of conjugation. Understanding the
      potential versatility of RNAs and their various roles in gene regulatory networks
      will allow us to better understand how cells regulate complex behavior.
      IMPORTANCE: Bacteria use RNA to regulate gene expression by a variety of
      mechanisms. The prgQ and prgX operons of pCF10, a conjugative plasmid of
      Enterococcus faecalis, have been shown to negatively regulate one another by a
      variety of mechanisms. One of these mechanisms involves Anti-Q, a small RNA from
      the prgX operon that prevents gene expression from the prgQ operon. In this work,
      we find that Qs, an RNA from the prgQ operon, negatively regulates gene
      expression from the prgX operon. These findings have a number of implications.
      (i) The Anti-Q and Qs RNAs act by different mechanisms, highlighting the variety
      of ways in which bacteria can regulate gene expression using RNAs. (ii)
      Reciprocal regulation between operons mediated by small RNAs has not been
      previously described, deepening our understanding of how bacteria regulate
      complex behavior. (iii) Additional roles for Qs have been described,
      demonstrating the versatility of this RNA.

PMID- 21954307
TI  - Dynamic virulence: real-time assessment of intracellular pathogenesis links
      Cryptococcus neoformans phenotype with clinical outcome.
AB  - While a myriad of studies have examined host factors that predispose persons to
      infection with the opportunistic fungal pathogen Cryptococcus neoformans,
      comparatively little has been done to examine how virulence factor differences
      among cryptococcal isolates may impact outcome. In the recent report by Alanio et
      al. (A. Alanio, M. Desnos-Ollivier, and F. Dromer, mBio 2:e00158-11, 2011), novel
      flow cytometry-based techniques were employed to demonstrate an association
      between the phenotype of C. neoformans-macrophage interactions, as measured by
      phagocytosis and intracellular replication, and patient outcomes, as determined
      by positive cultures on therapy and survival. These experiments establish that
      the prognosis of patients with cryptococcosis is influenced by the phenotypic
      properties of the infecting fungal isolate.

PMID- 21954308
TI  - Determination of low-molecular mass phenols in red wines: the influence of chips,
      staves and micro-oxygenation aging tank.
AB  - The aim of this study is to assess the use of polymeric cartridges with diode
      array detection to extract the main low-molecular mass phenolic compounds from
      red wine samples. This method expanded and improved permitted to quantify 20
      compounds in red wines made and aged under different conditions. These conditions
      included aging in barrels and in tanks with chips or staves as well as micro
      oxygenation. The study of wine development during its wood storage period and the
      compounds transferred from the wood to the wine during this period provide useful
      important information concerning the impact of wine aging methods on the chemical
      makeup of the resulting wines. The main compounds that differentiated wine aging
      systems were identified to be 5-hydroxymethyl-2 furaldehyde, gallic acid, p
      hydroxybenzoic aldehyde, syringic acid and sinapic acid.

PMID- 21954306
TI  - Necrotic enteritis-derived Clostridium perfringens strain with three closely
      related independently conjugative toxin and antibiotic resistance plasmids.
AB  - The pathogenesis of avian necrotic enteritis involves NetB, a pore-forming toxin
      produced by virulent avian isolates of Clostridium perfringens type A. To
      determine the location and mobility of the netB structural gene, we examined a
      derivative of the tetracycline-resistant necrotic enteritis strain EHE-NE18, in
      which netB was insertionally inactivated by the chloramphenicol and thiamphenicol
      resistance gene catP. Both tetracycline and thiamphenicol resistance could be
      transferred either together or separately to a recipient strain in plate matings.
      The separate transconjugants could act as donors in subsequent matings, which
      demonstrated that the tetracycline resistance determinant and the netB gene were
      present on different conjugative elements. Large plasmids were isolated from the
      transconjugants and analyzed by high-throughput sequencing. Analysis of the
      resultant data indicated that there were actually three large conjugative
      plasmids present in the original strain, each with its own toxin or antibiotic
      resistance locus. Each plasmid contained a highly conserved 40-kb region that
      included plasmid replication and transfer regions that were closely related to
      the 47-kb conjugative tetracycline resistance plasmid pCW3 from C. perfringens.
      The plasmids were as follows: (i) a conjugative 49-kb tetracycline resistance
      plasmid that was very similar to pCW3, (ii) a conjugative 82-kb plasmid that
      contained the netB gene and other potential virulence genes, and (iii) a 70-kb
      plasmid that carried the cpb2 gene, which encodes a different pore-forming toxin,
      beta2 toxin. IMPORTANCE: The anaerobic bacterium Clostridium perfringens can
      cause an avian gastrointestinal disease known as necrotic enteritis. Disease
      pathogenesis is not well understood, although the plasmid-encoded pore-forming
      toxin NetB, is an important virulence factor. In this work, we have shown that
      the plasmid that carries the netB gene is conjugative and has a 40-kb region that
      is very similar to replication and transfer regions found within each of the
      sequenced conjugative plasmids from C. perfringens. We also showed that this
      strain contained two additional large plasmids that were also conjugative and
      carried a similar 40-kb region. One of these plasmids encoded beta2 toxin, and
      the other encoded tetracycline resistance. To our knowledge, this is the first
      report of a bacterial strain that carries three closely related but different
      independently conjugative plasmids. These results have significant implications
      for our understanding of the transmission of virulence and antibiotic resistance
      genes in pathogenic bacteria.

PMID- 21954309
TI  - Efficacy of different washing solutions and contact times on the microbial
      quality and safety of fresh-cut paprika.
AB  - The role of different washing solutions and contact times was investigated to
      determine their use as potential sanitizers for maintaining the microbial quality
      and food safety of fresh-cut paprika. Samples were cut into small pieces, washed
      for both 90 and 180 s by different washing solutions: tap water, chlorinated
      water (100 mg/L and pH 6.5-7), electrolyzed water (pH 7.2) and ozonized water (4
      mg/L). Then, samples were packaged in 50 um polypropylene bags and stored at 5 
      degrees C for 12 days, followed by an evaluation of the antimicrobial efficacy of
      the treatments. Various quality and safety parameters, such as gas composition,
      color, off-odor, electrical conductivity and microbial numbers, were evaluated
      during storage. Results revealed insignificant differences in gas composition,
      and no off-odor was observed in any of the samples during the storage period.
      However, longer contact time resulted in slightly lower hue angle value than a
      short one for all washing solutions. Moreover, samples washed with ozone washings
      showed lower electrolyte leakage than other washing solutions. Samples washed for
      longer contact time except those washed in ozonized water showed increased
      microbial numbers during storage. Hence, it has been concluded that longer
      contact time with ozone has positive effects, whereas the other washing solutions
      adversely affect the microbial quality and safety aspects of fresh-cut paprika.

PMID- 21954311
TI  - Effect of air velocity on kinetics of thin layer carrot pomace drying.
AB  - Carrot pomace is a by-product obtained during carrot juice processing. Thin layer
      carrot pomace drying was performed in a laboratory scale hot air forced
      convective dryer. The drying experiments were carried out at the air velocity of
      0.5, 0.7 and 1.0 m/s at air temperatures from 60 to 75  degrees C. It was
      observed that whole drying process of carrot pomace took place in a falling rate
      period except a very short accelerating period at the beginning. Mathematical
      models were tested to fit drying data of carrot pomace. The best fit model was
      observed on the basis of R2, Chi-square and RMSE values. R2 values for all the
      selected models were above 0.9783. The average values of effective diffusivity
      ranged from 2.61 * 10(-9) to 3.64 * 10(-9) m2/s.

PMID- 21954312
TI  - Timeline of a journal: 50 years of Food Science and Technology International.

PMID- 21954313
TI  - In vitro antioxidant and radical-scavenging capacities of Citrullus colocynthes
      (L) and Artemisia absinthium extracts using promethazine hydrochloride radical
      cation and contemporary assays.
AB  - A new, quick and economical decolorization assay based upon the generation of a
      radical cation made from promethazine hydrochloride (PMZH) is described for
      screening of antioxidant activity of plants/herbal extracts. PMZH radical
      cations, produced through a reaction between PMZH and potassium persulfate
      (K(2)S(2)O(8)) in phosphoric acid medium, have maximum absorption at 515 nm in
      their first-order derivative spectrum. Theconcentrations of chromagen and
      K(2)S(2)O(8) were optimized (final concentration of PMZH and K2S2O8 were 0.166 mM
      and 0.11 mM, respectively) for better stability and sensitivity of the radical
      cation produced. Agood linear correlation was found between the percentage
      inhibition and the increasing amounts of standard antioxidants, with correlation
      coefficients ranging from 0.989 to 0.999. The newly developed assay was employed
      to evaluate the antioxidant capacity of Citrullus colocynthes L. and Artemisia
      absinthium extracts. The proposed assay involved a more stable radical cation and
      required only 1 h for preparation of a working solution in comparison to the 2,2'
      azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical cation
      decolorizaion assay, which was reported to be less sensitive at low pH and almost
      12-16 h were required for preparation of a working ABTS solution. Other assays
      employed to evaluate the antioxidant potential andradical-scavenging capacities
      of the extracts were the ferric-reducing antioxidant power, 2,2'-diphenyl-1
      picrylhydrazyl radical scavenging, total phenolic contents assay, total flavonoid
      contents and metal-chelating activity assays, and the lipid peroxidation value in
      linoleic acid emulsion systems. The results indicate that boththe plants have
      potent free radical-scavenging activity and the ability to prevent lipid
      peroxidation and radical chain reactions.

PMID- 21954314
TI  - Application of Baranyi function to model the antibacterial properties of solvent
      extract from Irish York cabbage against food spoilage and pathogenic bacteria.
AB  - Cabbage is a rich source of a number of bioactive compounds such as flavonoids,
      glucosinolates and their breakdown products which may have antibacterial,
      antioxidant and anticancer properties. Outer green leaves of York cabbage were
      extracted with 60% methanol, ethanol or acetone. Antibacterial activities of
      vacuum dried crude extracts were estimated against a number of Gram-positive and
      Gram-negative food spoilage and food pathogenic bacteria. The crude extracts
      showed a broad spectrum of antibacterial activities but 60% methanol extract
      exhibited the highest antibacterial effect. Complete growth inhibition for
      Listeria monocytogenes was achieved with an extract concentration of 1.4%,
      whereas a two-fold concentration was required to achieve a reduction of 75% and
      64% for Salmonella abony and Pseudomonas aeruginosa, respectively. For
      Enterococcus faecalis methanolic extract showed a weak inhibition only (31%). The
      lower concentrations of methanolic extract from York cabbage prolonged the lag
      phase and reduced both the exponential growth rate and final population densities
      of the culture. Survival of the micro-organisms in presence of methanolic extract
      was mathematically modeled using Baranyi model equations.

PMID- 21954315
TI  - Optimization of thermal processing of canned mussels.
AB  - The design and optimization of thermal processing of solid-liquid food mixtures,
      such as canned mussels, requires the knowledge of the thermal history at the
      slowest heating point. In general, this point does not coincide with the
      geometrical center of the can, and the results show that it is located along the
      axial axis at a height that depends on the brine content. In this study, a
      mathematical model for the prediction of the temperature at this point was
      developed using the discrete transfer function approach. Transfer function
      coefficients were experimentally obtained, and prediction equations fitted to
      consider other can dimensions and sampling interval. This model was coupled with
      an optimization routine in order to search for different retort temperature
      profiles to maximize a quality index. Both constant retort temperature (CRT) and
      variable retort temperature (VRT; discrete step-wise and exponential) were
      considered. In the CRT process, the optimal retort temperature was always between
      134  degrees C and 137  degrees C, and high values of thiamine retention were
      achieved. A significant improvement in surface quality index was obtained for
      optimal VRT profiles compared to optimal CRT. The optimization procedure shown in
      this study produces results that justify its utilization in the industry.

PMID- 21954316
TI  - Progress in antimicrobial activities of chitin, chitosan and its
      oligosaccharides: a systematic study needs for food applications.
AB  - In recent years, active biomolecules such as chitosan and its derivatives are
      undergoing a significant and very fast development in food application area. Due
      to recent outbreaks of contaminations associated with food products, there have
      been growing concerns regarding the negative environmental impact of packaging
      materials of antimicrobial biofilms, which have been studied. Chitosan has a
      great potential for a wide range of applications due to its biodegradability,
      biocompatibility, antimicrobial activity, nontoxicity and versatile chemical and
      physical properties. It can be formed into fibers, films, gels, sponges, beads or
      nanoparticles. Chitosan films have been used as a packaging material for the
      quality preservation of a variety of foods. Chitosan has high antimicrobial
      activities against a wide variety of pathogenic and spoilage microorganisms,
      including fungi, and Gram-positive and Gram-negative bacteria. A tremendous
      effort has been made over the past decade to develop and test films with
      antimicrobial properties to improve food safety and shelf-life. This review
      highlights the preparation, mechanism, antimicrobial activity, optimization of
      biocide properties of chitosan films and applications including biocatalysts for
      the improvement of quality and shelf-life of foods.

PMID- 21954317
TI  - Modeling of the process of moisture loss during the storage of dried apricots.
AB  - Moisture content is a reference parameter for dried food because the growth of
      most microorganisms is inhibited below certain water activity levels. In
      addition, it has a determining influence on the evolution of important
      parameters, such as color and flavor, and on other properties and deterioration
      reactions, such as texture, oxidation processes and nutritional value. During the
      storage of some dried fruits, moisture is produced due to Maillard reactions and
      exchanged with the surrounding environment through the packaging. The evolution
      of dried foods during their shelf life depends on the storage conditions. The aim
      of this study is to analyze the evolution of the moisture content in dried
      apricots packaged in different types of containers, namely glass and thermosealed
      polypropylene trays. The samples were stored at constant temperatures: 5, 15, 25
      and 35  degrees C and were analyzed periodically over a period of 12 months. The
      sorption isotherms of apricots used in this study were also determined. In order
      to model how the moisture evolved, an empirical kinetic model was tested. This
      model considers both water transfer from the fruit and also water production as a
      result of the Maillard processes. The explained variance was higher than 95% in
      the samples stored in trays, which were thermosealed with film.

PMID- 21954318
TI  - Biophysical investigations into the interactions of endotoxins with bile acids.
AB  - The interaction of selected endotoxin preparations (lipid A from Erwinia
      carotovora and LPS Re and Ra from Salmonella enterica sv. Minnesota strains R595
      and R60, respectively) with selected bile acids was investigated biophysically.
      Endotoxin aggregates were analyzed for their gel-to-liquid crystalline phase
      behavior, the type of their aggregates, the conformation of particular functional
      groups, and their Zeta potential in the absence and presence of the bile acids by
      applying Fourier-transform infrared spectroscopy, differential scanning
      calorimetry, measurements of the electrophoretic mobility, and synchrotron
      radiation X-ray scattering. In addition, the ability of the endotoxins to induce
      cytokines in human mononuclear cells was tested in the absence and presence of
      varying concentrations of bile acids. The data show that the endotoxin:bile acid
      interaction is not governed by Coulomb forces, rather a hydrophobic interaction
      takes place. This leads to an enhanced formation of the inherent cubic aggregate
      structures of the endotoxins, concomitant with a slight disaggregation, as
      evidenced by freeze-fracture electron microscopy. Parallel to this, the addition
      of bile acids increased the bioactivity of lipid A and, to a lower degree, also
      that of the tested rough mutant LPS at lower concentrations of the endotoxin
      preparation, a finding similar as reported for the interaction of other agents
      such as hemoglobin. These data imply that there are general mechanisms that
      govern the expression of biological activities of endotoxins.

PMID- 21954319
TI  - Mental health professionals' attitudes towards people with mental illness: do
      they differ from attitudes held by people with mental illness?
AB  - AIMS: Studies investigating mental health professionals' attitudes towards people
      with mental illness are scarce and there is a lack of comparative studies
      including both patients' and mental health professionals' attitudes. The aim of
      the present study was to investigate mental health staff's attitudes towards
      people with mental illness and compare these with the attitudes of patients in
      contact with mental health services. A further aim was to relate staff attitudes
      to demographic and work characteristics. METHODS: A cross-sectional study was
      performed including 140 staff and 141 patients. The study included a random
      sample of outpatients in contact with mental health services in the southern part
      of Sweden and staff working in these services. Attitudes were investigated using
      a questionnaire covering beliefs of devaluation and discrimination of people with
      a mental illness. RESULTS: Negative attitudes were prevalent among staff. Most
      negative attitudes concerned whether an employer would accept an application for
      work, willingness to date a person who had been hospitalized, and hiring a
      patient to take care of children. Staff treating patients with a psychosis or
      working in inpatient settings had the most negative attitudes. Patient attitudes
      were overall similar to staff attitudes and there were significant differences in
      only three out of 12 dimensions. Patients' most negative attitudes were in the
      same area as the staff's. CONCLUSIONS: This study points to the suggestion that
      mental health care staff may hold negative attitudes and beliefs about people
      with mental illness with tentative implications for treatment of the patient and
      development and implementation of evidence-based services. Since patients and
      staff in most respects share these beliefs, it is essential to develop
      interventions that have an impact on both patients and staff, enabling a more
      recovery-oriented staff-patient relationship.

PMID- 21954320
TI  - Response of Euphausia pacifica to small-scale shear in turbulent flow over a sill
      in a fjord.
AB  - Zooplankton in the ocean respond to visual and hydro-mechanical cues such as
      small-scale shear in turbulent flow. In addition, they form strong aggregations
      where currents intersect sloping bottoms. Strong and predictable tidal currents
      over a sill in Knight Inlet, Canada, make it an ideal location to investigate
      biological behaviour in turbulent cross-isobath flow. We examine acoustic data
      (38, 120 and 200 kHz) collected there during the daylight hours, when the
      dominant zooplankters, Euphausia pacifica have descended into low light levels at
      ~90 m. As expected, these data reveal strong aggregations at the sill. However,
      they occur consistently 10-20 m below the preferred light depth of the animals.
      We have constructed a simple model of the flow to investigate this phenomenon.
      Tracks of individual animals are traced in the flow and a variety of zooplankton
      behaviours tested. Our results indicate that the euphausiids must actively swim
      downward when they encounter the bottom boundary layer (bbl) to reproduce the
      observed downward shift in aggregation patterns. We suggest that this behaviour
      is cued by the small-scale shear in the bbl. Furthermore, this behaviour is
      likely to enhance aggregations found in strong flows at sills and on continental
      shelves.

PMID- 21954321
TI  - Highly Photoluminescent and Stable Aqueous ZnS Quantum Dots.
AB  - We report an all-aqueous synthesis of highly photoluminescent and stable ZnS
      quantum dots (QDs) with water as the medium, i.e. first synthesizing ZnS QDs with
      3-mercaptopropionic acid (MPA) as the capping molecule, followed by replacing
      some of MPA with (3-mercaptopropyl) trimethoxysilane (MPS). The resultant MPS
      replaced ZnS QDs were about 5 nm in size with a cubic zinc blende crystalline
      structure, and had both MPA and MPS on the surface as confirmed by the Fourier
      Transform Infrared (FTIR) spectroscopy. They exhibited blue trap-state emissions
      around 415 nm and a quantum yield (QY) of 75% with Rhodamine 101 as the
      reference, and remained stable for more than 60 days under the ambient
      conditions. Through the capping molecule replacement procedure, the MPS-replaced
      ZnS QDs avoided the shortcomings of both the MPA-ZnS QDs and the MPS-ZnS QDs, and
      acquired the advantages of strong photoluminescence and good stability, which are
      important to the QDs' applications especially for bioimaging.

PMID- 21954322
TI  - Asymmetric multi-component reactions: convenient access to acyclic stereocenters
      and functionalized cyclopentenoids.
AB  - Asymmetric multi-component reactions of optically active phenyl dihydrofuran,
      keto ester or N-tosyl imino ester, and allylsilane provided functionalized phenyl
      tetrahydrofurans with multiple stereogenic centers diastereoselectively. Cleavage
      of the resulting substituted tetrahydrofurans readily provided acyclic
      derivatives with three contiguous asymmetric centers via an acyloxycarbenium ion
      intermediate. Ring closing olefin metathesis, using Grubbs catalyst, afforded
      functionalized cyclopentene derivatives in optically active form. A one pot
      tandem tetrahydrofuran ring cleavage followed by ring closing olefin metathesis
      also provided functionalized cyclopentenes in good yield.

PMID- 21954323
TI  - Interplay of dynamic transcription and chromatin remodeling: lessons from yeast.
AB  - Regulation of transcription involves dynamic rearrangements of chromatin
      structure. The budding yeast Saccharomyces cerevisiae has a variety of highly
      conserved factors necessary for these reconstructions. Chromatin remodelers,
      histone modifiers and histone chaperones directly associate to promoters and open
      reading frames of exposed genes and facilitate activation and repression of
      transcription. We compare two distinct patterns of induced transcription:
      Sustained transcribed genes switch to an activated state where they remain as
      long as the induction signal is present. In contrast, single pulsed transcribed
      genes show a quick and strong induction pulse resulting in high transcript levels
      followed by adaptation and repression to basal levels. We discuss intensively
      studied promoters and coding regions from both groups for their co-factor
      requirements during transcription. Interplay between chromatin restructuring
      factors and dynamic transcription is highly variable and locus dependent.

PMID- 21954324
TI  - Anti-fatigue properties of tartary buckwheat extracts in mice.
AB  - Anti-fatigue properties of tartary buckwheat extracts (TBE) was investigated in
      male Kunming mice. The animals were divided into four groups. The first group,
      designated as the control group (control), was administered with distilled water
      by gavage every day for 28 days. The other three groups, designated as TBE
      treatment groups, were administered with TBE of 60, 120 and 240 mg/kg body
      weight, respectively, by gavage every day for 28 days. Exhaustive swimming time,
      blood lactic acid (BLA), blood urea nitrogen (BUN), tissue glycogen, glutathione
      peroxidase (GPx) and superoxide dismutase (SOD) of mice after swimming were
      determined. The results showed that tartary buckwheat extracts had anti-fatigue
      properties, which extended the exhaustive swimming time of mice, effectively
      inhibiting the increase of BLA, decreasing the level of BUN, increasing the
      tissue glycogen content and the activities of SOD and GPx of mice. However,
      further study is needed to elucidate the exact mechanism of the effect of TBE on
      fatigue.

PMID- 21954325
TI  - Molecular recognition effects in atomistic models of imprinted polymers.
AB  - In this article we present a model for molecularly imprinted polymers, which
      considers both complexation processes in the pre-polymerization mixture and
      adsorption in the imprinted structures within a single consistent framework. As a
      case study we investigate MAA/EGDMA polymers imprinted with pyrazine and
      pyrimidine. A polymer imprinted with pyrazine shows substantial selectivity
      towards pyrazine over pyrimidine, thus exhibiting molecular recognition, whereas
      the pyrimidine imprinted structure shows no preferential adsorption of the
      template. Binding sites responsible for the molecular recognition of pyrazine
      involve one MAA molecule and one EGDMA molecule, forming associations with the
      two functional groups of the pyrazine molecule. Presence of these specific sites
      in the pyrazine imprinted system and lack of the analogous sites in the
      pyrimidine imprinted system is directly linked to the complexation processes in
      the pre-polymerization solution. These processes are quite different for pyrazine
      and pyrimidine as a result of both enthalpic and entropic effects.

PMID- 21954326
TI  - Solvolyses of benzoyl chlorides in weakly nucleophilic media.
AB  - Rate constants and activations parameters are reported for solvolyses of p-Z
      substituted benzoyl chlorides (1, Z = OMe, Me, H, and Cl) in 97% w/w
      hexafluoroisopropanol-water (97H). Additional kinetic data are reported for
      solvolyses in acetic and formic acids. Plots of log k vs. sigma(p) in 97H are
      consistent with previous research showing that a cationic reaction channel is
      dominant, even for solvolyses of 1, Z = NO(2). A benzoyl cation intermediate was
      trapped by Friedel-Crafts reaction with 1,3,5-trimethoxybenzene in
      hexafluoroisopropanol. The results are explained by an S(N)2-S(N)1 spectrum of
      mechanisms with variations in nucleophilic solvent assistance. Ab initio
      calculations of heterolytic bond dissociation energies of various chloro- and
      fluoro-substituted and other benzoyl chlorides are correlated with log k for
      solvolyses.

PMID- 21954327
TI  - Evaluation of in vitro and in vivo depigmenting activity of raspberry ketone from
      Rheum officinale.
AB  - Melanogenesis inhibition by raspberry ketone (RK) from Rheum officinale was
      investigated both in vitro in cultivated murine B16 melanoma cells and in vivo in
      zebrafish and mice. In B16 cells, RK inhibited melanogenesis through a post
      transcriptional regulation of tyrosinase gene expression, which resulted in down
      regulation of both cellular tyrosinase activity and the amount of tyrosinase
      protein, while the level of tyrosinase mRNA transcription was not affected. In
      zebrafish, RK also inhibited melanogenesis by reduction of tyrosinase activity.
      In mice, application of a 0.2% or 2% gel preparation of RK applied to mouse skin
      significantly increased the degree of skin whitening within one week of
      treatment. In contrast to the widely used flavoring properties of RK in perfumery
      and cosmetics, the skin-whitening potency of RK has been demonstrated in the
      present study. Based on our findings reported here, RK would appear to have high
      potential for use in the cosmetics industry.

PMID- 21954328
TI  - Genetic characterization of five hatchery populations of the Pacific Abalone
      (Haliotis discus hannai) using microsatellite markers.
AB  - The Pacific abalone, Haliotis discus hannai, is a popular food in Eastern Asia.
      Aquacultural production of this species has increased because of recent resource
      declines, the growing consumption, and ongoing government-operated stock release
      programs. Therefore, the genetic characterization of hatchery populations is
      necessary to maintain the genetic diversity of this species and to develop more
      effective aquaculture practices. We analyzed the genetic structures of five
      cultured populations in Korea using six microsatellite markers. The number of
      alleles per locus ranged from 15 to 64, with an average of 23.5. The mean
      observed and expected heterozygosities were 0.797 and 0.904, respectively. The
      inbreeding coefficient F(IS) ranged from 0.054 to 0.184 (mean F(IS) = 0.121 +/-
      0.056). The genetic differentiation across all populations was low but
      significant (overall F(ST) = 0.009, P < 0.01). Pairwise multilocus F(ST) tests,
      estimates of genetic distance, and phylogenetic and principal component analyses
      did not show a consistent relationship between geographic and genetic distances.
      These results could reflect extensive aquaculture, the exchange of breeds and
      eggs between hatcheries and/or genetic drift due to intensive breeding practices.
      Thus, for optimal resource management, the genetic variation of hatchery stocks
      should be monitored and inbreeding controlled within the abalone stocks that are
      being released every year. This genetic information will be useful for the
      management of both H. discus hannai fisheries and the aquaculture industry.

PMID- 21954329
TI  - Intermediates in the protein folding process: a computational model.
AB  - The paper presents a model for simulating the protein folding process in silico.
      The two-step model (which consists of the early stage-ES and the late stage-LS)
      is verified using two proteins, one of which is treated (according to
      experimental observations) as the early stage and the second as an example of the
      LS step. The early stage is based solely on backbone structural preferences,
      while the LS model takes into account the water environment, treated as an
      external hydrophobic force field and represented by a 3D Gauss function. The
      characteristics of 1ZTR (the ES intermediate, as compared with 1ENH, which is the
      LS intermediate) confirm the link between the gradual disappearance of ES
      characteristics in LS structural forms and the simultaneous emergence of LS
      properties in the 1ENH protein. Positive verification of ES and LS
      characteristics in these two proteins (1ZTR and 1ENH respectively) suggest
      potential applicability of the presented model to in silico protein folding
      simulations.

PMID- 21954330
TI  - Silibinin causes apoptosis and cell cycle arrest in some human pancreatic cancer
      cells.
AB  - Silibinin, an effective anti-cancer and chemopreventive agent in various
      epithelial cancer models, has been reported to inhibit cancer cell growth through
      mitogenic signaling pathways. However, whether it can inhibit human pancreatic
      carcinoma growth and what are the underlying mechanisms is still not well
      elucidated. Here, we evaluated the inhibitory proliferation effects of Silibinin
      in pancreatic carcinoma growth and examined whether Silibinin modulates cell
      cycle and apoptosis. Our results indicate that Silibinin effectively inhibited
      the pancreatic carcinoma AsPC-1, BxPC-3 and Panc-1 cells' proliferation and
      caused apoptosis. Silibinin induced a decrease in S phase and cell cycle arrest
      in G1 phase in AsPC-1 cells, but had no obvious changes in BxPC-3 and Panc-1 cell
      cycle. Furthermore, these results suggest that Silibinin might be a candidate
      chemopreventive agent for pancreatic carcinoma therapy.

PMID- 21954331
TI  - Green synthesis and characterization of silver/chitosan/polyethylene glycol
      nanocomposites without any reducing agent.
AB  - This paper presents the green synthesis of silver nanoparticles (Ag NPs) in
      aqueous medium. This method was performed by reducing AgNO(3) in different
      stirring times of reaction at a moderate temperature using green agents, chitosan
      (Cts) and polyethylene glycol (PEG). In this work, silver nitrate (AgNO(3)) was
      used as the silver precursor while Cts and PEG were used as the solid support and
      polymeric stabilizer. The properties of Ag/Cts/PEG nanocomposites (NCs) were
      studied under different stirring times of reaction. The developed Ag/Cts/PEG NCs
      were then characterized by the ultraviolet-visible (UV-Vis) spectroscopy, X-ray
      diffraction (XRD), transmission electron microscopy (TEM), scanning electron
      microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy.

PMID- 21954332
TI  - The chemical composition and nitrogen distribution of Chinese yak (Maiwa) milk.
AB  - The paper surveyed the chemical composition and nitrogen distribution of Maiwa
      yak milk, and compared the results with reference composition of cow milk.
      Compared to cow milk, yak milk was richer in protein (especially whey protein),
      essential amino acids, fat, lactose and minerals (except phosphorus). The
      contents of some nutrients (total protein, lactose, essential amino acids and
      casein) were higher in the warm season than in the cold season. Higher ratios of
      total essential amino acids/total amino acids (TEAA/TAA) and total essential
      amino acids/total non essential amino acids (TEAA/TNEAA) were found in the yak
      milk from the warm season. However its annual average ratio of EAA/TAA and that
      of EAA/NEAA were similar to those of cow milk. Yak milk was rich in calcium and
      iron (p < 0.05), and thus may serve as a nutritional ingredient with a potential
      application in industrial processing.

PMID- 21954333
TI  - In vitro and in vivo antioxidant properties of the plant-based supplement
      greens+TM.
AB  - Dietary antioxidants play an important role against oxidation, an underlying
      mechanism in the incidence of chronic diseases. Greens+ is a commercially
      available preparation containing a variety of plant-derived ingredients. The aim
      of the current study was to evaluate the antioxidant potential of the methanolic
      extract of greens+ powder using in vitro and in vivo techniques. In vitro studies
      were conducted using a liposome model system to simulate biological cell
      membranes. Total antioxidant potential and polyphenol content of the herbal
      preparation was measured. For in vivo analysis, 10 healthy human subjects
      consumed either three or six teaspoons of greens+ per day for four weeks. Blood
      samples were analyzed at baseline and at the conclusion of the treatment period
      for total antioxidant capacity, polyphenol content, protein, lipid and LDL
      oxidation, and the level of glutathione peroxidase. Results showed that greens+
      supplementation was well tolerated and increased serum antioxidant potential at
      higher levels of intake in a dose-dependent manner. HPLC analysis showed the
      presence of quercetin, apigenin, kaempferol and luteolin in the supplement.
      Plasma analysis indicated the presence of kaempferol only. A statistically
      significant (p < 0.05) reduction in protein and lipid oxidation was observed.
      Based on its antioxidant properties, the results suggest that greens+ might play
      a role in reducing the risk of chronic diseases involving a burden of oxidative
      damage.

PMID- 21954334
TI  - Experimental and theoretical Electron Paramagnetic Resonance (EPR) study on the
      temperature-dependent structural changes of methylsulfanylmethane.
AB  - Methylsulfonylmethane (or dimethyl sulfone), a naturally produced and vitally
      important organosulfur compound in living organisms, was irradiated with gamma
      rays, and the produced radicals were investigated using electron paramagnetic
      resonance spectroscopy at different temperatures. The structure and behavior of
      the radical changed when the temperatures varied. The hyperfine splitting of the
      CH(3) group was small, and the (33)S splitting was relatively high between 80 and
      -50  degrees C. When the temperature was between -50 and -160  degrees C, the
      (33)S splitting became small and the CH(3) splitting was higher. However, the
      group kept rotating; therefore, only the isotropic splitting values were
      measured, and the g-values were anisotropic. When the temperature decreased below
      -180  degrees C, the CH(3) group stopped rotating, and the hydrogen splitting
      values became nonequivalent due to an inhomogeneous electron distribution. The
      observed structures can be explained by referring to both the experimental and
      theoretically calculated values reported.

PMID- 21954335
TI  - The Langmuir-Blodgett technique as a tool for homeotropic alignment of
      fluorinated liquid crystals mixed with arachidic acid.
AB  - Some fluoro-substituted liquid crystals mixed with arachidic acid in monolayers
      formed at air-liquid (Langmuir films) and air-solid substrate (Langmuir-Blodgett
      films) interfaces were investigated. Molecular organization in Langmuir films was
      determined on the basis of the analysis of the shape of the surface pressure-mean
      molecular area isotherm and observations made by means of a Brewster angle
      microscope. It was found that in the compression process the liquid crystal
      molecules are pushed out towards the top of the first monolayer being in direct
      contact with the subphase. Langmuir films were transferred onto the quartz
      substrates at various surface pressures and mono- and multilayered Langmuir
      Blodgett films were obtained. The films were characterized using electronic
      absorption measurements. The conditions for obtaining the homeotropic orientation
      of the liquid crystal molecules were determined.

PMID- 21954336
TI  - A new benzofuran glucoside from Ficus tikoua Bur.
AB  - From the water-soluble portion of the methanol extract of stems of Ficus tikoua
      Bur., a new benzofuran glucoside, named 6-carboxyethyl-5-hydroxybenzofuran 5-O
      beta-d-glucopyranoside (1), together with one known benzofuran glucoside (2) were
      isolated. Their structures were elucidated by 1D and 2D ((1)H-(1)H COSY, HMQC,
      and HMBC) NMR spectroscopy and HRMS techniques. The antioxidant activities of the
      isolated compounds were assayed based on the scavenging activities of DPPH free
      radical. Compounds 1 and 2 exhibited moderate antioxidant activities, and the
      IC(50) values were 242.8 MUg.mL(-1) and 324.9 MUg.mL(-1), respectively.

PMID- 21954337
TI  - Low expression of TBX4 predicts poor prognosis in patients with stage II
      pancreatic ductal adenocarcinoma.
AB  - This study was designed to investigate the expression of the T-box transcription
      factor 4 (TBX4), a tumor biomarker that was previously identified by proteomics,
      in pancreatic ductal adenocarcinoma (PDAC) and evaluate its clinical utility as a
      potential prognostic biomarkers for PDAC. The expression of TBX4 was detected in
      77 stage II PDAC tumors by immunohistochemistry, and the results were analyzed
      with regard to clinicopathological characteristics and overall survival.
      Moreover, Tbx4 promoter methylation status in primary PDAC tumors and normal
      adjacent pancreas tissues was measured by bisulfite sequencing. Among 77 stage II
      PDAC tumors, 48 cases (62.3%) expressed TBX4 at a high level. No significant
      correlation between TBX4 expression and other clinicopathological parameters,
      except tumor grade and liver metastasis recurrence, was found. The survival of
      patients with TBX4-high expression was significantly longer than those with TBX4
      low expression (P = 0.010). In multivariate analysis, low TBX4 expression was an
      independent prognostic factor for overall survival in patients with stage II
      PDAC. TBX4 promoter methylation status was frequently observed in both PDAC and
      normal adjacent pancreas. We conclude that a low level of TBX4 expression
      suggests a worse prognosis for patients with stage II PDAC. Down-regulation of
      the TBX4 gene in pancreas is less likely to be regulated by DNA methylation.

PMID- 21954338
TI  - Interaction of human serum album and C60 aggregates in solution.
AB  - An important property of C(60) in aquatic ecotoxicology is that it can form
      stable aggregates with nanoscale dimensions, namely nC(60). Aggregation allows
      fullerenes to remain suspended for a long time, and the reactivity of individual
      C(60) is substantially altered in this aggregate form. Herein, we investigated
      the interaction of nC(60) and human serum album (HSA) using the methods of
      fluorescence, fluorescence dynamics, circular dichroism (CD), and site marker
      competitive experiments. We proposed a binding model consistent with the
      available experimental results for the interactions of nC(60) with HSA. During
      the interaction process, the structure and conformation of HSA were affected,
      leading to functional changes of drug binding sites of HSA.

PMID- 21954339
TI  - Transient co-expression of post-transcriptional gene silencing suppressors for
      increased in planta expression of a recombinant anthrax receptor fusion protein.
AB  - Potential epidemics of infectious diseases and the constant threat of
      bioterrorism demand rapid, scalable, and cost-efficient manufacturing of
      therapeutic proteins. Molecular farming of tobacco plants provides an alternative
      for the recombinant production of therapeutics. We have developed a transient
      production platform that uses Agrobacterium infiltration of Nicotiana benthamiana
      plants to express a novel anthrax receptor decoy protein (immunoadhesin), CMG2
      Fc. This chimeric fusion protein, designed to protect against the deadly anthrax
      toxins, is composed of the von Willebrand factor A (VWA) domain of human
      capillary morphogenesis 2 (CMG2), an effective anthrax toxin receptor, and the Fc
      region of human immunoglobulin G (IgG). We evaluated, in N. benthamiana intact
      plants and detached leaves, the expression of CMG2-Fc under the control of the
      constitutive CaMV 35S promoter, and the co-expression of CMG2-Fc with nine
      different viral suppressors of post-transcriptional gene silencing (PTGS): p1,
      p10, p19, p21, p24, p25, p38, 2b, and HCPro. Overall, transient CMG2-Fc
      expression was higher on intact plants than detached leaves. Maximum expression
      was observed with p1 co-expression at 3.5 days post-infiltration (DPI), with a
      level of 0.56 g CMG2-Fc per kg of leaf fresh weight and 1.5% of the total soluble
      protein, a ten-fold increase in expression when compared to absence of
      suppression. Co-expression with the p25 PTGS suppressor also significantly
      increased the CMG2-Fc expression level after just 3.5 DPI.

PMID- 21954340
TI  - Resveratrol protects against 2-bromopropane-induced apoptosis and disruption of
      embryonic development in blastocysts.
AB  - 2-Bromopropane (2-BP) is used as an alternative to ozone-depleting cleaning
      solvents. Previously, we reported that 2-BP has cytotoxic effects on mouse
      blastocysts and is associated with defects in subsequent development. In the
      present work, we show that 2-BP induces apoptosis in the inner cell mass of mouse
      blastocysts, and inhibits cell proliferation. Both effects are suppressed by
      resveratrol, a grape-derived phytoalexin with known antioxidant and anti
      inflammatory properties. 2-BP-treated blastocysts displayed lower levels of
      implantation (compared to controls) when plated on culture dishes in vitro, and a
      reduced ability to proceed to later stages of embryonic development. Pretreatment
      with resveratrol prevented 2-BP-induced disruption of embryonic development, both
      in vitro and in vivo. Further investigation of these processes revealed that 2-BP
      directly promotes ROS generation, loss of mitochondrial membrane potential (MMP),
      and activation of caspase-3, whereas resveratrol effectively blocks 2-BP-induced
      ROS production and the accompanying apoptotic biochemical changes. Our results
      collectively imply that 2-BP triggers the mitochondrion-dependent apoptotic
      pathway via ROS generation, and the antioxidant activity of resveratrol prevents
      2-BP-induced toxicity.

PMID- 21954341
TI  - Investigation of the structure requirement for 5-HT6 binding affinity of
      arylsulfonyl derivatives: a computational study.
AB  - 5-HT(6) receptor has been implicated in a series of diseases including anxiety,
      depression, schizophrenia and cognitive dysfunctions. 5-HT(6) ligands have been
      reported to play a significant role in the treatment for central nervous system
      (CNS) diseases. Presently, a large series of 223 5-HT(6) ligands were studied
      using a combinational method by 3D-QSAR, molecular docking and molecular dynamics
      calculations for further improvement of potency. The optimal 3D models exhibit
      satisfying statistical results with r(2) (ncv), q(2) values of 0.85 and 0.50 for
      CoMFA, 0.81 and 0.53 for CoMSIA, respectively. Their predictive powers were
      validated by external test set, showing r(2) (pred) of 0.71 and 0.76. The contour
      maps also provide a visual representation of contributions of steric,
      electrostatic, hydrophobic and hydrogen bond fields as well as the prospective
      binding models. In addition, the agreement between 3D-QSAR, molecular docking and
      molecular dynamics simulation proves the rationality of the developed models.
      These results, we hope, may be helpful in designing novel and potential 5-HT(6)
      ligands.

PMID- 21954342
TI  - Comparative clinical study of Bactigras and Telfa AMD for skin graft donor-site
      dressing.
AB  - The Bactigras((r)) paraffin tulle coated with chlorhexidine is normally used for
      the treatment of donor-site wounds in burn patients who received split-thickness
      skin grafts in several centers. It has some disadvantages, such as adhesion to
      wound surfaces and pain from the irritation caused by this dressing. The Telfa
      AMD((r)), a non-adherent wound dressing which consists of absorbent cotton fibers
      impregnated with polyhexamethylene biguanide enclosed in a sleeve of
      thermoplastic polymers, is a new option for donor-site wound care which causes
      less adherence to the wound. The purpose of this study was to compare clinical
      efficacy of these two dressings for the management of donor-site wounds. Thirty
      two patients who received split-thickness skin grafts by donor site harvesting
      from the thigh were enrolled in this study and randomized into two groups
      receiving either the Bactigras((r)) or the Telfa AMD((r)) wound treatment. Re
      epithelialization, pain, infection and cost-effectiveness analyses were compared
      between both groups. The results showed that there was no significant difference
      in age, area of donor sites or length of hospital stays between the groups (p >
      0.05). However, the day of re-epithelialization (>=90%) was significantly shorter
      in patients treated with the Telfa AMD((r)) compared to the Bactigras((r)) group
      (14.00 +/- 3.05 vs. 9.25 +/- 1.88 days for Bactigras((r)) and Telfa AMD((r))
      groups, respectively, p < 0.001). The average pain score was also significantly
      lower in the Telfa AMD((r)) group (1.57 +/- 0.55 vs. 4.70 +/- 1.16, p < 0.001).
      There was no difference in the cost of treatment between the groups (4.64 +/-
      1.97 vs. 5.72 +/- 2.54 USD, p = 0.19). This study indicated that the Telfa
      AMD((r)) was an effective dressing for the treatment of donor-site wounds.

PMID- 21954343
TI  - Potential antibacterial activity of carvacrol-loaded poly(DL-lactide-co
      glycolide) (PLGA) nanoparticles against microbial biofilm.
AB  - The ability to form biofilms contributes significantly to the pathogenesis of
      many microbial infections, including a variety of ocular diseases often
      associated with the biofilm formation on foreign materials. Carvacrol (Car.) is
      an important component of essential oils and recently has attracted much
      attention pursuant to its ability to promote microbial biofilm disruption. In the
      present study Car. has been encapsulated in poly(dl-lactide-co-glycolide (PLGA)
      nanocapsules in order to obtain a suitable drug delivery system that could
      represent a starting point for developing new therapeutic strategies against
      biofilm-associated infections, such as improving the drug effect by associating
      an antimicrobial agent with a biofilm viscoelasticity modifier.

PMID- 21954344
TI  - A pilot study of the association of tumor necrosis factor alpha polymorphisms
      with psoriatic arthritis in the Romanian population.
AB  - Tumor necrosis factor alpha (TNF-alpha) is an important pro-inflammatory cytokine
      implicated in the pathogenesis of psoriatic arthritis. We have performed a case
      control association study of three TNF-alpha gene polymorphisms in a group of
      Romanian psoriatic arthritis patients versus ethnically matched controls. A
      second group of patients with undifferentiated spondyloarthritis was used in
      order to look for similarities in the genetic background of the two rheumatic
      disorders. The -857C/T polymorphism was associated with susceptibility to
      psoriatic arthritis in our population at the individual level (p = 0.03, OR 1.65,
      95% CI 1.05-2.57) and in combined haplotypes with the -238G/A and -308G/A SNPs.
      Regarding the investigated polymorphisms and derived haplotypes, no potential
      association was found with the susceptibility to undifferentiated
      spondyloarthritis in Romanian patients.

PMID- 21954345
TI  - Effect of Cistanches Herba aqueous extract on bone loss in ovariectomized rat.
AB  - To assess the ability of traditional Chinese medicine Cistanches Herba extract
      (CHE) to prevent bone loss in the ovariectomized (OVX) rat, Cistanches Herba
      extract (CHE) was administered intragastrically to the rats. Female rats were
      anesthetized with pentobarbital sodium (40 mg kg(-1), i.p.), and their ovaries
      were removed bilaterally. The rats in the sham-operated group were anesthetized,
      laparotomized, and sutured without removing their ovaries. After 1 week of
      recovery from surgery, the OVX rats were randomly divided into three groups and
      orally treated with H(2)O (OVX group) or CHE (100 or 200 mg kg(-1) daily) for 3
      months. The sham-operated group (n = 8) was orally treated with H(2)O. After 3
      months, the total body bone mineral density (BMD), bone mineral content (BMC),
      Bone biomechanical index, blood mineral levels and blood antioxidant enzymes
      activities were examined in sham-operated, ovariectomized and Cistanches Herba
      extract treated rats. Results showed that Cistanches Herba extract treatment
      significantly dose-dependently enhanced bone mineral density (BMD), bone mineral
      content (BMC), maximum load, displacement at maximum load, stress at maximum
      load, load at auto break, displacement at auto break, and stress at auto break,
      and blood antioxidant enzymes activities, decreased blood Ca, Zn and Cu levels
      compared to the OVX group. This experiment demonstrates that the administration
      of Cistanches Herba extract to ovariectomized rats reverses bone loss and
      prevents osteoporosis.

PMID- 21954346
TI  - Identification and role of regulatory non-coding RNAs in Listeria monocytogenes.
AB  - Bacterial regulatory non-coding RNAs control numerous mRNA targets that direct a
      plethora of biological processes, such as the adaption to environmental changes,
      growth and virulence. Recently developed high-throughput techniques, such as
      genomic tiling arrays and RNA-Seq have allowed investigating prokaryotic cis- and
      trans-acting regulatory RNAs, including sRNAs, asRNAs, untranslated regions (UTR)
      and riboswitches. As a result, we obtained a more comprehensive view on the
      complexity and plasticity of the prokaryotic genome biology. Listeria
      monocytogenes was utilized as a model system for intracellular pathogenic
      bacteria in several studies, which revealed the presence of about 180 regulatory
      RNAs in the listerial genome. A regulatory role of non-coding RNAs in survival,
      virulence and adaptation mechanisms of L. monocytogenes was confirmed in
      subsequent experiments, thus, providing insight into a multifaceted modulatory
      function of RNA/mRNA interference. In this review, we discuss the identification
      of regulatory RNAs by high-throughput techniques and in their functional role in
      L. monocytogenes.

PMID- 21954347
TI  - Combined 3D-QSAR and docking modelling study on indolocarbazole series compounds
      as Tie-2 inhibitors.
AB  - Tie-2, a kind of endothelial cell tyrosine kinase receptor, is required for
      embryonic blood vessel development and tumor angiogenesis. Several compounds that
      showed potent activity toward this attractive anticancer drug target in the assay
      have been reported. In order to investigate the structure-activity correlation of
      indolocarbazole series compounds and modify them to improve their selectivity and
      activity, 3D-QSAR models were built using CoMFA and CoMSIA methods and molecular
      docking was used to check the results. Based on the common sketch align, two good
      QSAR models with high predictabilities (CoMFA model: q(2) = 0.823, r(2) = 0.979;
      CoMSIA model: q(2) = 0.804, r(2) = 0.967) were obtained and the contour maps
      obtained from both models were applied to identify the influence on the
      biological activity. Molecular docking was then used to confirm the results.
      Combined with the molecular docking results, the detail binding mode between the
      ligands and Tie-2 was elucidated, which enabled us to interpret the structure
      activity relationship. These satisf actory results not only offered help to
      comprehend the action mechanism of indolocarbazole series compounds, but also
      provide new information for the design of new potent inhibitors.

PMID- 21954348
TI  - Alert-QSAR. Implications for electrophilic theory of chemical carcinogenesis.
AB  - Given the modeling and predictive abilities of quantitative structure activity
      relationships (QSARs) for genotoxic carcinogens or mutagens that directly affect
      DNA, the present research investigates structural alert (SA) intermediate
      predicted correlations A(SA) of electrophilic molecular structures with observed
      carcinogenic potencies in rats (observed activity, A = Log[1/TD(50)], i.e.,
      [Formula: see text]). The present method includes calculation of the recently
      developed residual correlation of the structural alert models, i.e., [Formula:
      see text]. We propose a specific electrophilic ligand-receptor mechanism that
      combines electronegativity with chemical hardness-associated frontier principles,
      equality of ligand-reagent electronegativities and ligand maximum chemical
      hardness for highly diverse toxic molecules against specific receptors in rats.
      The observed carcinogenic activity is influenced by the induced SA-mutagenic
      intermediate effect, alongside Hansch indices such as hydrophobicity (LogP),
      polarizability (POL) and total energy (Etot), which account for molecular
      membrane diffusion, ionic deformation, and stericity, respectively. A possible
      QSAR mechanistic interpretation of mutagenicity as the first step in genotoxic
      carcinogenesis development is discussed using the structural alert
      chemoinformation and in full accordance with the Organization for Economic Co
      operation and Development QSAR guidance principles.

PMID- 21954349
TI  - Enhancing single molecule imaging in optofluidics and microfluidics.
AB  - Microfluidics and optofluidics have revolutionized high-throughput analysis and
      chemical synthesis over the past decade. Single molecule imaging has witnessed
      similar growth, due to its capacity to reveal heterogeneities at high spatial and
      temporal resolutions. However, both resolution types are dependent on the signal
      to noise ratio (SNR) of the image. In this paper, we review how the SNR can be
      enhanced in optofluidics and microfluidics. Starting with optofluidics, we
      outline integrated photonic structures that increase the signal emitted by single
      chromophores and minimize the excitation volume. Turning then to microfluidics,
      we review the compatible functionalization strategies that reduce noise stemming
      from non-specific interactions and architectures that minimize bleaching and
      blinking.

PMID- 21954350
TI  - Self-assembly of protein monolayers engineered for improved monoclonal
      immunoglobulin G binding.
AB  - Bacterial outer membrane proteins, along with a filling lipid molecule can be
      modified to form stable self-assembled monolayers on gold. The transmembrane
      domain of Escherichia coli outer membrane protein A has been engineered to create
      a scaffold protein to which functional motifs can be fused. In earlier work we
      described the assembly and structure of an antibody-binding array where the Z
      domain of Staphylococcus aureus protein A was fused to the scaffold protein.
      Whilst the binding of rabbit polyclonal immunoglobulin G (IgG) to the array is
      very strong, mouse monoclonal IgG dissociates from the array easily. This is a
      problem since many immunodiagnostic tests rely upon the use of mouse monoclonal
      antibodies. Here we describe a strategy to develop an antibody-binding array that
      will bind mouse monoclonal IgG with lowered dissociation from the array. A novel
      protein consisting of the scaffold protein fused to two pairs of Z domains
      separated by a long flexible linker was manufactured. Using surface plasmon
      resonance the self-assembly of the new protein on gold and the improved binding
      of mouse monoclonal IgG were demonstrated.

PMID- 21954352
TI  - Syntheses and self-assembling behaviors of pentagonal conjugates of tryptophane
      zipper-forming peptide.
AB  - Pentagonal conjugates of tryptophane zipper-forming peptide (CKTWTWTE) with a
      pentaazacyclopentadecane core (Pentagonal-Gly-Trpzip and Pentagonal-Ala-Trpzip)
      were synthesized and their self-assembling behaviors were investigated in water.
      Pentagonal-Gly-Trpzip self-assembled into nanofibers with the width of about 5 nm
      in neutral water (pH 7) via formation of tryptophane zipper, which irreversibly
      converted to nanoribbons by heating. In contrast, Pentagonal-Ala-Trpzip formed
      irregular aggregates in water.

PMID- 21954351
TI  - Major Histocompatibility Complex (MHC) markers in conservation biology.
AB  - Human impacts through habitat destruction, introduction of invasive species and
      climate change are increasing the number of species threatened with extinction.
      Decreases in population size simultaneously lead to reductions in genetic
      diversity, ultimately reducing the ability of populations to adapt to a changing
      environment. In this way, loss of genetic polymorphism is linked with extinction
      risk. Recent advances in sequencing technologies mean that obtaining measures of
      genetic diversity at functionally important genes is within reach for
      conservation programs. A key region of the genome that should be targeted for
      population genetic studies is the Major Histocompatibility Complex (MHC). MHC
      genes, found in all jawed vertebrates, are the most polymorphic genes in
      vertebrate genomes. They play key roles in immune function via immune-recognition
      and -surveillance and host-parasite interaction. Therefore, measuring levels of
      polymorphism at these genes can provide indirect measures of the immunological
      fitness of populations. The MHC has also been linked with mate-choice and
      pregnancy outcomes and has application for improving mating success in captive
      breeding programs. The recent discovery that genetic diversity at MHC genes may
      protect against the spread of contagious cancers provides an added impetus for
      managing and protecting MHC diversity in wild populations. Here we review the
      field and focus on the successful applications of MHC-typing for conservation
      management. We emphasize the importance of using MHC markers when planning and
      executing wildlife rescue and conservation programs but stress that this should
      not be done to the detriment of genome-wide diversity.

PMID- 21954353
TI  - A comparative reverse docking strategy to identify potential antineoplastic
      targets of tea functional components and binding mode.
AB  - The main functional components of green tea, such as epigallocatechin gallate
      (EGCG), epigallocatechin (EGC), epicatechin gallate (ECG) and epicatechin (EC),
      are found to have a broad antineoplastic activity. The discovery of their targets
      plays an important role in revealing the antineoplastic mechanism. Therefore, to
      identify potential target proteins for tea polyphenols, we have taken a
      comparative virtual screening approach using two reverse docking systems, one
      based on Autodock software and the other on Tarfisdock. Two separate in silico
      workflows were implemented to derive a set of target proteins related to human
      diseases and ranked by the binding energy score. Several conventional clinically
      important proteins with anti-tumor effects are screened out from the PDTD protein
      database as the potential receptors by both procedures. To further analyze the
      validity of docking results, we study the binding mode of EGCG and the potential
      target protein Leukotriene A4 hydrolase in detail. We indicate that interactions
      mediated by electrostatic and hydrogen bond play a key role in ligand binding.
      EGCG binds to the enzyme with certain orientation and conformation that is
      suitable for nucleophilic attacks by several electrical residues inside the
      enzyme's activity cavity. This study provides useful information for studying the
      antitumor mechanism of tea's functional components. The comparative reverse
      docking strategy presented generates a tractable set of antineoplastic proteins
      for future experimental validation as drug targets against tumors.

PMID- 21954355
TI  - Effects of nitrogen fertilization on synthesis of primary and secondary
      metabolites in three varieties of Kacip Fatimah (Labisia pumila Blume).
AB  - A split plot 3 by 4 experiment was designed to examine the impact of 15-week
      variable levels of nitrogen fertilization (0, 90, 180 and 270 kg N/ha) on the
      characteristics of total flavonoids (TF), total phenolics (TP), total non
      structurable carbohydrate (TNC), net assimilation rate, leaf chlorophyll content,
      carbon to nitrogen ratio (C/N), phenyl alanine lyase activity (PAL) and protein
      content, and their relationships, in three varieties of Labisia pumila Blume
      (alata, pumila and lanceolata). The treatment effects were solely contributed by
      nitrogen application; there was neither varietal nor interaction effect observed.
      As nitrogen levels increased from 0 to 270 kg N/ha, the production of TNC was
      found to decrease steadily. Production of TF and TP reached their peaks under 0
      followed by 90, 180 and 270 kg N/ha treatment. However, net assimilation rate was
      enhanced as nitrogen fertilization increased from 0 to 270 kg N/ha. The increase
      in production of TP and TF under low nitrogen levels (0 and 90 kg N/ha) was found
      to be correlated with enhanced PAL activity. The enhancement in PAL activity was
      followed by reduction in production of soluble protein under low nitrogen
      fertilization indicating more availability of amino acid phenyl alanine (phe)
      under low nitrogen content that stimulate the production of carbon based
      secondary metabolites (CBSM). The latter was manifested by high C/N ratio in L.
      pumila plants.

PMID- 21954356
TI  - Sinanodonta woodiana (Mollusca: Bivalvia: Unionidae): isolation and
      characterization of the first microsatellite markers.
AB  - Sinanodonta woodiana (Lea, 1834) is a large Unionid species with a real invasion
      success. It colonized Europe, Central America, the Indonesian Islands and
      recently North America. The species life cycle involves a larval parasitic stage
      on freshwater fish species which contributes to the spread of the mussel. In this
      paper we describe, for the first time, eight polymorphic microsatellite loci for
      the species Sinanodonta woodiana. The genetic screening of individuals confirmed
      that all loci were highly polymorphic. The number of alleles per locus ranged
      from 7 to 14 and the observed heterozygosity ranged from 0.650 to 0.950. These
      loci should prove useful to study the species population genetics which could
      help to infer important aspects of the invasion process.

PMID- 21954354
TI  - Mechanisms of mycotoxin-induced neurotoxicity through oxidative stress-associated
      pathways.
AB  - Among many mycotoxins, T-2 toxin, macrocyclic trichothecenes, fumonisin B(1)
      (FB(1)) and ochratochin A (OTA) are known to have the potential to induce
      neurotoxicity in rodent models. T-2 toxin induces neuronal cell apoptosis in the
      fetal and adult brain. Macrocyclic trichothecenes bring about neuronal cell
      apoptosis and inflammation in the olfactory epithelium and olfactory bulb. FB(1)
      induces neuronal degeneration in the cerebral cortex, concurrent with disruption
      of de novo ceramide synthesis. OTA causes acute depletion of striatal dopamine
      and its metabolites, accompanying evidence of neuronal cell apoptosis in the
      substantia nigra, striatum and hippocampus. This paper reviews the mechanisms of
      neurotoxicity induced by these mycotoxins especially from the viewpoint of
      oxidative stress-associated pathways.

PMID- 21954357
TI  - FK506-Binding protein 22 from a psychrophilic bacterium, a cold shock-inducible
      peptidyl prolyl isomerase with the ability to assist in protein folding.
AB  - Adaptation of microorganisms to low temperatures remains to be fully elucidated.
      It has been previously reported that peptidyl prolyl cis-trans isomerases
      (PPIases) are involved in cold adaptation of various microorganisms whether they
      are hyperthermophiles, mesophiles or phsycrophiles. The rate of cis-trans
      isomerization at low temperatures is much slower than that at higher temperatures
      and may cause problems in protein folding. However, the mechanisms by which
      PPIases are involved in cold adaptation remain unclear. Here we used FK506
      binding protein 22, a cold shock protein from the psychrophilic bacterium
      Shewanella sp. SIB1 (SIB1 FKBP22) as a model protein to decipher the involvement
      of PPIases in cold adaptation. SIB1 FKBP22 is homodimer that assumes a V-shaped
      structure based on a tertiary model. Each monomer consists of an N-domain
      responsible for dimerization and a C-catalytic domain. SIB1 FKBP22 is a typical
      cold-adapted enzyme as indicated by the increase of catalytic efficiency at low
      temperatures, the downward shift in optimal temperature of activity and the
      reduction in the conformational stability. SIB1 FKBP22 is considered as foldase
      and chaperone based on its ability to catalyze refolding of a cis-proline
      containing protein and bind to a folding intermediate protein, respectively. The
      foldase and chaperone activites of SIB1 FKBP22 are thought to be important for
      cold adaptation of Shewanella sp. SIB1. These activities are also employed by
      other PPIases for being involved in cold adaptation of various microorganisms.
      Despite other biological roles of PPIases, we proposed that foldase and chaperone
      activities of PPIases are the main requirement for overcoming the cold-stress
      problem in microorganisms due to folding of proteins.

PMID- 21954358
TI  - New aspects of mitochondrial Uncoupling Proteins (UCPs) and their roles in
      tumorigenesis.
AB  - Uncoupling proteins (UCPs) belong to a family of mitochondrial carrier proteins
      that are present in the mitochondrial inner membrane. UCP1 was first identified
      followed by its two homologs, UCP2 and UCP3. The physiological functions of UCP
      include lowering mitochondrial membrane potential and dissipating metabolic
      energy as heat. However, UCP can be dysregulated and may contribute to the
      pathogenesis of metabolic disorders and obesity. Recent studies suggest that UCP
      also plays a role in neurodegenerative diseases and atherosclerosis. In addition,
      the widely expressed UCP, UCP2, has been shown to be upregulated in a number of
      aggressive human cancers. One mechanism of UCP2 upregulation in these cancers is
      due to oxidative stress, and elevated UCP2 in turn reduces oxidative stress,
      which provides a growth advantage for these cancers. Nevertheless, new studies
      suggest UCP2 may interact with oncogenes and tumor suppressor genes, providing a
      potential new mechanism of how UCP2 contributes to cancer development. In this
      review, the evidence supporting the role of UCPs in diseases other than diabetes
      and obesity, the reports on how UCP is regulated in cancer cells, and how UCP may
      regulate p53 will be discussed.

PMID- 21954359
TI  - Characterization of thermophilic halotolerant Aeribacillus pallidus TD1 from Tao
      Dam Hot Spring, Thailand.
AB  - The bacterial strain TD1 was isolated from Tao Dam hot spring in Thailand. Strain
      TD1 was Gram positive, rod-shaped, aerobic, motile, and endospore forming. The
      cell was 2.0-40 MUm in length and about 0.4 MUm in diameter. The optimum growth
      occurred at 55-60  degrees C and at pH 7-8. Strain TD1 was able to grow on medium
      containing up to 10% NaCl. The DNA G+C content was 38.9 mol%. The cellular fatty
      acid content was mainly C(16:0), which comprised 25.04% of the total amount of
      cellular fatty acid. 16S rDNA showed 99% identity to Aeribacillus pallidus DSM
      3670(T). Bayesian tree analysis strongly supported the idea that strain TD1 is
      affiliated with genus Aeribacillus, as Aeribacillus pallidus strain TD1. Although
      the 16S rDNA of A. pallidus strain TD1 is similar to that of A. pallidus DSM
      3670(T), some physiological properties and the cellular fatty acid profiles
      differ significantly. A. pallidus strain TD1 can produce extracellular pectate
      lyase, which has not been reported elsewhere for other bacterial strains in the
      genus Aeribacillus. A. pallidus strain TD1 may be a good candidate as a pectate
      lyase producer, which may have useful industrial applications.

PMID- 21954360
TI  - Reviewing ligand-based rational drug design: the search for an ATP synthase
      inhibitor.
AB  - Following major advances in the field of medicinal chemistry, novel drugs can now
      be designed systematically, instead of relying on old trial and error approaches.
      Current drug design strategies can be classified as being either ligand- or
      structure-based depending on the design process. In this paper, by describing the
      search for an ATP synthase inhibitor, we review two frequently used approaches in
      ligand-based drug design: The pharmacophore model and the quantitative structure
      activity relationship (QSAR) method. Moreover, since ATP synthase ligands are
      potentially useful drugs in cancer therapy, pharmacophore models were constructed
      to pave the way for novel inhibitor designs.

PMID- 21954361
TI  - Microwave-assisted extraction of oleanolic acid and ursolic acid from Ligustrum
      lucidum Ait.
AB  - Oleanolic acid and ursolic acid are the main active components in fruit of
      Ligustrum lucidum Ait, and possess anticancer, antimutagenic, anti-inflammatory,
      antioxidative and antiprotozoal activities. In this study, microwave-assisted
      extraction of oleanolic acid and ursolic acid from Ligustrum lucidum was
      investigated with HPLC-photodiode array detection. Effects of several
      experimental parameters, such as type and concentration of extraction solvent,
      ratio of liquid to material, microwave power, extraction temperature and
      microwave time, on the extraction efficiencies of oleanolic acid and ursolic acid
      from Ligustrum lucidum were evaluated. The influence of experimental parameters
      on the extraction efficiency of ursolic acid was more significant than that of
      oleanolic acid (p < 0.05). The optimal extraction conditions were 80% ethanol
      aqueous solution, the ratio of material to liquid was 1:15, and extraction for 30
      min at 70  degrees C under microwave irradiation of 500 W. Under optimal
      conditions, the yields of oleanolic acid and ursolic acid were 4.4 +/- 0.20 mg/g
      and 5.8 +/- 0.15 mg/g, respectively. The results obtained are helpful for the
      full utilization of Ligustrum lucidum, which also indicated that microwave
      assisted extraction is a very useful method for extraction of oleanolic acid and
      ursolic acid from plant materials.

PMID- 21954362
TI  - Effect of filler size and temperature on packing stress and viscosity of resin
      composites.
AB  - The objective of this study was to investigate the effect of filler size on the
      packing stress and viscosity of uncured resin-composite at 23  degrees C and 37 
      degrees C. A precision instrument used was designed upon the penetrometer
      principle. Eight resin-composite materials were tested. Packing-stress ranged
      from 2.60 to 0.43 MPa and viscosity ranged from 2.88 to 0.02 MPa.s at 23  degrees
      C. Values for both properties were reduced significantly at 37  degrees C.
      Statistical analysis, by ANOVA and post hoc methods, were carried out to check
      any significant differences between materials tested (P < 0.05). CONCLUSIONS:
      Filler size and distribution will affect the viscosity and packing of resin
      composites during cavity placement.

PMID- 21954363
TI  - Spin transition sensors based on beta-amino-acid 1,2,4-triazole derivative.
AB  - A beta-aminoacid ester was successfully derivatized to yield to 4H-1,2-4-triazol
      4-yl-propionate (betaAlatrz) which served as a neutral bidentate ligand in the 1D
      coordination polymer [Fe(betaAlatrz)(3)](CF(3)SO(3))(2).0.5H(2)O (1.0.5H(2)O).
      The temperature dependence of the high-spin molar fraction derived from (57)Fe
      Mossbauer spectroscopy recorded on cooling below room temperature reveals an
      exceptionally abrupt single step transition between high-spin and low-spin states
      with a hysteresis loop of width 4 K (T(c) (?) = 232 K and T(c) (?) = 228 K) in
      agreement with magnetic susceptibility measurements. The material presents
      striking reversible thermochromism from white, at room temperature, to pink on
      quench cooling to liquid nitrogen, and acts as an alert towards temperature
      variations. The phase transition is of first order, as determined by differential
      scanning calorimetry, with transition temperatures matching the ones determined
      by SQUID and Mossbauer spectroscopy. The freshly prepared sample of 1.0.5H(2)O,
      dried in air, was subjected to annealing at 390 K, and the obtained white
      compound [Fe(betaAlatrz)(3)](CF(3)SO(3))(2) (1) was found to exhibit a similar
      spin transition curve however much temperature was increased by (T(c) (?) = 252 K
      and T(c) (?) = 248 K). The removal of lattice water molecules from 1.0.5H(2)O is
      not accompanied by a change of the morphology and of the space group, and the
      chain character is preserved. However, an internal pressure effect stabilizing
      the low-spin state is evidenced.

PMID- 21954364
TI  - Structure and dynamics of reentrant nematics: any open questions after almost 40
      years?
AB  - Liquid crystals have attracted enormous interest because of the variety of their
      phases and richness of their application. The interplay of general physical
      symmetries and specific molecular features generates a myriad of different
      phenomena. A surprising behavior of liquid crystals is the reentrancy of phases
      as temperature, pressure, or concentration are varied. Here, we review the main
      experimental facts and the different theoretical scenarios that have guided the
      understanding of bulk reentrant nematics. Recently, some computer simulations of
      a system confined to nanoscopic scales have found new dynamical features of the
      reentrant nematic phase. We discuss this prediction in relation with the
      available experimental evidence on reentrant nematics and with the dynamics of
      liquids in strongly confined environments.

PMID- 21954365
TI  - p66Shc aging protein in control of fibroblasts cell fate.
AB  - Reactive oxygen species (ROS) are wieldy accepted as one of the main factors of
      the aging process. These highly reactive compounds modify nucleic acids, proteins
      and lipids and affect the functionality of mitochondria in the first case and
      ultimately of the cell. Any agent or genetic modification that affects ROS
      production and detoxification can be expected to influence longevity. On the
      other hand, genetic manipulations leading to increased longevity can be expected
      to involve cellular changes that affect ROS metabolism. The 66-kDa isoform of the
      growth factor adaptor Shc (p66Shc) has been recognized as a relevant factor to
      the oxygen radical theory of aging. The most recent data indicate that p66Shc
      protein regulates life span in mammals and its phosphorylation on serine 36 is
      important for the initiation of cell death upon oxidative stress. Moreover, there
      is strong evidence that apart from aging, p66Shc may be implicated in many
      oxidative stress-associated pathologies, such as diabetes, mitochondrial and
      neurodegenerative disorders and tumorigenesis. This article summarizes recent
      knowledge about the role of p66Shc in aging and senescence and how this protein
      can influence ROS production and detoxification, focusing on studies performed on
      skin and skin fibroblasts.

PMID- 21954366
TI  - The hsp 16 gene of the probiotic Lactobacillus acidophilus is differently
      regulated by salt, high temperature and acidic stresses, as revealed by reverse
      transcription quantitative PCR (qRT-PCR) analysis.
AB  - Small heat shock proteins (sHsps) are ubiquitous conserved chaperone-like
      proteins involved in cellular proteins protection under stressful conditions. In
      this study, a reverse transcription quantitative PCR (RT-qPCR) procedure was
      developed and used to quantify the transcript level of a small heat shock gene
      (shs) in the probiotic bacterium Lactobacillus acidophilus NCFM, under stress
      conditions such as heat (45  degrees C and 53  degrees C), bile (0.3% w/v),
      hyperosmosis (1 M and 2.5 M NaCl), and low pH value (pH 4). The shs gene of L.
      acidophilus NCFM was induced by salt, high temperature and acidic stress, while
      repression was observed upon bile stress. Analysis of the 5' noncoding region of
      the hsp16 gene reveals the presence of an inverted repeat (IR) sequence
      (TTAGCACTC-N9-GAGTGCTAA) homologue to the controlling IR of chaperone expression
      (CIRCE) elements found in the upstream regulatory region of Gram-positive heat
      shock operons, suggesting that the hsp16 gene of L. acidophilus might be
      transcriptionally controlled by HrcA. In addition, the alignment of several small
      heat shock proteins identified so far in lactic acid bacteria, reveals that the
      Hsp16 of L. acidophilus exhibits a strong evolutionary relationship with members
      of the Lactobacillus acidophilus group.

PMID- 21954368
TI  - Preparation and microcosmic structural analysis of recording coating on inkjet
      printing media.
AB  - Preparation of recording coating on inkjet printing (RC-IJP) media was proposed.
      The microstructure and roughness of RC-IJP was analyzed by scanning electron
      microscopy (SEM) and atomic force microscope (AFM). The surface infiltration
      process of RC-IJP was studied by a liquid infiltration instrument. The
      distribution of C, O and Si composites on recording coating surface is analyzed
      by energy dispersive spectrum (EDS). The transmission electron microscopy (TEM)
      analysis showed that the nanoscale silica could be dissolved uniformly in water.
      Finally, the print color is shown clearly by the preparative recording coating.

PMID- 21954367
TI  - Self-assembly in the ferritin nano-cage protein superfamily.
AB  - Protein self-assembly, through specific, high affinity, and geometrically
      constraining protein-protein interactions, can control and lead to complex
      cellular nano-structures. Establishing an understanding of the underlying
      principles that govern protein self-assembly is not only essential to appreciate
      the fundamental biological functions of these structures, but could also provide
      a basis for their enhancement for nano-material applications. The ferritins are a
      superfamily of well studied proteins that self-assemble into hollow cage-like
      structures which are ubiquitously found in both prokaryotes and eukaryotes.
      Structural studies have revealed that many members of the ferritin family can
      self-assemble into nano-cages of two types. Maxi-ferritins form hollow spheres
      with octahedral symmetry composed of twenty-four monomers. Mini-ferritins, on the
      other hand, are tetrahedrally symmetric, hollow assemblies composed of twelve
      monomers. This review will focus on the structure of members of the ferritin
      superfamily, the mechanism of ferritin self-assembly and the structure-function
      relations of these proteins.

PMID- 21954370
TI  - Estimation of the genetic diversity in tetraploid alfalfa populations based on
      RAPD markers for breeding purposes.
AB  - Alfalfa is an autotetraploid, allogamous and heterozygous forage legume, whose
      varieties are synthetic populations. Due to the complex nature of the species,
      information about genetic diversity of germplasm used in any alfalfa breeding
      program is most beneficial. The genetic diversity of five alfalfa varieties,
      involved in progeny tests at Institute of Field and Vegetable Crops, was
      characterized based on RAPD markers. A total of 60 primers were screened, out of
      which 17 were selected for the analysis of genetic diversity. A total of 156
      polymorphic bands were generated, with 10.6 bands per primer. Number and
      percentage of polymorphic loci, effective number of alleles, expected
      heterozygosity and Shannon's information index were used to estimate genetic
      variation. Variety Zuzana had the highest values for all tested parameters,
      exhibiting the highest level of variation, whereas variety RSI 20 exhibited the
      lowest. Analysis of molecular variance (AMOVA) showed that 88.39% of the total
      genetic variation was attributed to intra-varietal variance. The cluster analysis
      for individual samples and varieties revealed differences in their population
      structures: variety Zuzana showed a very high level of genetic variation, Banat
      and Ghareh were divided in subpopulations, while Pecy and RSI 20 were relatively
      uniform. Ways of exploiting the investigated germplasm in the breeding programs
      are suggested in this paper, depending on their population structure and
      diversity. The RAPD analysis shows potential to be applied in analysis of
      parental populations in semi-hybrid alfalfa breeding program in both, development
      of new homogenous germplasm, and identification of promising, complementary
      germplasm.

PMID- 21954369
TI  - Antioxidant, antimicrobial and antiproliferative activities of five lichen
      species.
AB  - The antioxidative, antimicrobial and antiproliferative potentials of the methanol
      extracts of the lichen species Parmelia sulcata, Flavoparmelia caperata, Evernia
      prunastri, Hypogymnia physodes and Cladonia foliacea were evaluated. The total
      phenolic content of the tested extracts varied from 78.12 to 141.59 mg of gallic
      acid equivalent (GA)/g of extract and the total flavonoid content from 20.14 to
      44.43 mg of rutin equivalent (Ru)/g of extract. The antioxidant capacities of the
      lichen extracts were determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals
      scavenging. Hypogymnia physodes with the highest phenolic content showed the
      strongest DPPH radical scavenging effect. Further, the antimicrobial potential of
      the lichen extracts was determined by a microdilution method on 29
      microorganisms, including 15 strains of bacteria, 10 species of filamentous fungi
      and 4 yeast species. A high antimicrobial activity of all the tested extracts was
      observed with more potent inhibitory effects on the growth of Gram (+) bacteria.
      The highest antimicrobial activity among lichens was demonstrated by Hypogymnia
      physodes and Cladonia foliacea. Finally, the antiproliferative activity of the
      lichen extracts was explored on the colon cancer adenocarcinoma cell line HCT-116
      by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) viability
      assay and acridine orange/ethidium bromide staining. The methanol extracts of
      Hypogymnia physodes and Cladonia foliacea showed a better cytotoxic activity than
      the other extracts. All lichen species showed the ability to induce apoptosis of
      HCT-116 cells.

PMID- 21954371
TI  - Divergent modes of integration: the Canadian way.
AB  - INTRODUCTION: The paper highlights key trajectories and outcomes of the recent
      policy developments toward integrated health care delivery systems in Quebec and
      Ontario in the primary care sector and in the development of regional networks of
      health and social services. It particularly explores how policy legacies,
      interests and cultures may be mitigated to develop and sustain different models
      of integrated health care that are pertinent to the local contexts. POLICY
      DEVELOPMENTS: In Quebec, three decades of iterative developments in health and
      social services evolved in 2005 into integrated centres for health and social
      services at the local levels (CSSSs). Four integrated university-based health
      care networks provide ultra-specialised services. Family Medicine Groups and
      network clinics are designed to enhance access and continuity of care. Ontario's
      Family Health Teams (2004) constitute an innovative public funding for private
      delivery model that is set up to enhance the capacity of primary care and to
      facilitate patient-based care. Ontario's Local Health Integration Networks
      (LHINs) with autonomous boards of provider organisations are intended to
      coordinate and integrate care. CONCLUSION: Integration strategies in Quebec and
      Ontario yield clinical autonomy and power to physicians while simultaneously
      making them key partners in change. Contextual factors combined with increased
      and varied forms of physician remunerations and incentives mitigated some of the
      challenges from policy legacies, interests and cultures. Virtual partnerships and
      accountability agreements between providers promise positive but gradual movement
      toward integrated health service systems.

PMID- 21954372
TI  - PRISMA: a good example of transferring research evidence into public policy.

PMID- 21954373
TI  - Buffer management to solve bed-blocking in the Netherlands 2000-2010. Cooperation
      from an integrated care chain perspective as a key success factor for managing
      patient flows.
AB  - INTRODUCTION: Bed-blocking problems in hospitals reflect how difficult and
      complex it is to move patients smoothly through the chain of care. In the
      Netherlands, during the first decade of the 21st century, some hospitals
      attempted to tackle this problem by using an Intermediate Care Department (ICD)
      as a buffer for bed-blockers. However, research has shown that ICDs do not
      sufficiently solve the bed-blocking problem and that bed-blocking is often caused
      by a lack of buffer management.  TOOL: Buffer management (BM) is a tool that
      endeavors to balance patient flow in the hospital to nursing home chain of care.
      RESULTS: Additional research has indicated that the absence of BM is not the
      result of providers' thinking that BM is unnecessary, unethical or impossible
      because of unpredictable patient flows. Instead, BM is hampered by a lack of
      cooperation between care providers. CONCLUSION: Although stakeholders recognize
      that cooperation is imperative, they often fail to take the actions necessary to
      realize cooperation. Our assumption is that this lack of willingness and ability
      to cooperate is the result of several impeding conditions as well as
      stakeholders' perceptions of these conditions and the persistence of their
      current routines, principles and beliefs (RPBs). DISCUSSION: We recommend
      simultaneously working on improving the conditions and changing stakeholders'
      perceptions and RPBs.

PMID- 21954374
TI  - Thickness Dependent Properties of Relaxor-PbTiO(3) Ferroelectrics for Ultrasonic
      Transducers.
AB  - The electrical properties of Pb(Mg(1/3)Nb(2/3))O(3)-PbTiO(3) (PMN-PT) based
      polycrystalline ceramics and single crystals were investigated as a function of
      scale ranging from 500 microns to 30 microns. Fine-grained PMN-PT ceramics
      exhibited comparable dielectric and piezoelectric properties to their coarse
      grained counterpart in the low frequency range (<10 MHz), but offered greater
      mechanical strength and improved property stability with decreasing thickness,
      corresponding to higher operating frequencies (>40 MHz). For PMN-PT single
      crystals, however, the dielectric and electromechanical properties degraded with
      decreasing thickness, while ternary Pb(In(1/2)Nb(1/2))O(3)-Pb(Mg(1/3)Nb(2/3))O(3)
      PbTiO(3) (PIN-PMN-PT) exhibited minimal size dependent behavior. The origin of
      property degradation of PMN-PT crystals was further studied by investigating the
      dielectric permittivity at high temperatures, and domain observations using
      optical polarized light microscopy. The results demonstrated that the thickness
      dependent properties of relaxor-PT ferroelectrics are closely related to the
      domain size with respect to the associated macroscopic scale of the samples.

PMID- 21954375
TI  - Instantaneous and cumulative influences of competition on impulsive choices in
      domestic chicks.
AB  - This study examined instantaneous and cumulative effects of competitive
      interactions on impulsiveness in the inter-temporal choices in domestic chicks.
      Chicks were trained to peck colored beads to gain delayed food rewards (1 or 6
      grains of millet delivered after a delay ranging between 0 and 4.5 s), and were
      tested in binary choices between a small-short delay option (SS) and a large-long
      delay alternative (LL). To examine whether competitive foraging instantaneously
      changes impulsiveness, we intraindividually compared choices between two
      consecutive tests in different contexts, one with competitors and another
      without. We found that (1) the number of the choice of LL was not influenced by
      competition in the tests, but (2) the operant peck latency was shortened by
      competition, suggesting a socially enhanced incentive for food. To further
      examine the lasting changes, two groups of chicks were consecutively trained and
      tested daily for 2 weeks according to a "behavioral titration" procedure, one
      with competitors and another without. Inter-group comparisons of the choices
      revealed that (3) choice impulsiveness gradually decreased along development,
      while (4) the chicks trained in competition maintained a higher level of
      impulsiveness. These results suggest that competitive foraging causes impulsive
      choices not by direct/contextual modification. Causal link between the
      instantaneous enhancement of incentive and the gradual effects on impulsiveness
      remains to be examined. Some (yet unspecified) factors may be indirectly
      involved.

PMID- 21954376
TI  - Early TBI-Induced Cytokine Alterations are Similarly Detected by Two Distinct
      Methods of Multiplex Assay.
AB  - Annually, more than a million persons experience traumatic brain injury (TBI) in
      the US and a substantial proportion of this population develop debilitating
      neurological disorders, such as, paralysis, cognitive deficits, and epilepsy.
      Despite the long-standing knowledge of the risks associated with TBI, no
      effective biomarkers or interventions exist. Recent evidence suggests a role for
      inflammatory modulators in TBI-induced neurological impairments. Current
      technological advances allow for the simultaneous analysis of the precise spatial
      and temporal expression patterns of numerous proteins in single samples which
      ultimately can lead to the development of novel treatments. Thus, the present
      study examined 23 different cytokines, including chemokines, in the ipsi and
      contralateral cerebral cortex of rats at 24 h after a fluid percussion injury
      (FPI). Furthermore, the estimation of cytokines were performed in a newly
      developed multiplex assay instrument, MAGPIX (Luminex Corp), and compared with an
      established instrument, Bio-Plex (Bio-Rad), in order to validate the newly
      developed instrument. The results show numerous inflammatory changes in the ipsi
      and contralateral side after FPI that were consistently reported by both
      technologies.

PMID- 21954377
TI  - Disinhibition-Mediated LTP in the Hippocampus is Synapse Specific.
AB  - Paired pre- and postsynaptic activity in area CA1 of the hippocampus induces long
      term inhibitory synaptic plasticity at GABAergic synapses. This pairing-induced
      GABAergic plasticity weakens synaptic inhibition due to a depolarization of the
      reversal potential for GABA(A) receptor-mediated currents (E(GABA)) through a
      decrease in the function of the neuron-specific K(+)-Cl(-) cotransporter KCC2.
      When pairing-induced GABAergic plasticity is induced at feed-forward inhibitory
      synapses in the CA1, the decrease in inhibition produces an increase in the
      amplitude of Schaffer collateral-mediated postsynaptic potentials in pyramidal
      neurons. This form of inhibitory synaptic plasticity is termed disinhibition
      mediated long-term potentiation (LTP). In the present study, we investigated
      whether disinhibition-mediated LTP is synapse specific. We performed these
      experiments in hippocampal slices prepared from adult Sprague Dawley rats. We
      found that the underlying depolarization of E(GABA) is not restricted to the
      paired pathway, but rather is expressed to the same extent at unpaired control
      pathways. However, the overall strength of GABAergic transmission is maintained
      at the unpaired pathway by a heterosynaptic increase in GABAergic conductance.
      The pairing-induced depolarization of E(GABA) at the paired and unpaired pathways
      required Ca(2+)-influx through both the L-type voltage-gated Ca(2+) channels and
      N-methyl-d-aspartic acid receptors. However, only Ca(2+)-influx through L-type
      channels was required for the increased conductance at the unpaired pathway. As a
      result of this increased GABAergic conductance, disinhibition-mediated LTP
      remains confined to the paired pathway and thus is synapse specific, suggesting
      it may be a novel mechanism for hippocampal-dependent learning and memory.

PMID- 21954378
TI  - In search of the structure of human olfactory space.
AB  - We analyze the responses of human observers to an ensemble of monomolecular
      odorants. Each odorant is characterized by a set of 146 perceptual descriptors
      obtained from a database of odor character profiles. Each odorant is therefore
      represented by a point in a highly multidimensional sensory space. In this work
      we study the arrangement of odorants in this perceptual space. We argue that
      odorants densely sample a two-dimensional curved surface embedded in the
      multidimensional sensory space. This surface can account for more than half of
      the variance of the perceptual data. We also show that only 12% of experimental
      variance cannot be explained by curved surfaces of substantially small
      dimensionality (<10). We suggest that these curved manifolds represent the
      relevant spaces sampled by the human olfactory system, thereby providing
      surrogates for olfactory sensory space. For the case of 2D approximation, we
      relate the two parameters on the curved surface to the physico-chemical
      parameters of odorant molecules. We show that one of the dimensions is related to
      eigenvalues of molecules' connectivity matrix, while the other is correlated with
      measures of molecules' polarity. We discuss the behavioral significance of these
      findings.

PMID- 21954380
TI  - Unpredictability and uncertainty in anxiety: a new direction for emotional timing
      research.

PMID- 21954379
TI  - Chemosensory learning in the cortex.
AB  - Taste is a primary reinforcer. Olfactory-taste and visual-taste association
      learning takes place in the primate including human orbitofrontal cortex to build
      representations of flavor. Rapid reversal of this learning can occur using a rule
      based learning system that can be reset when an expected taste or flavor reward
      is not obtained, that is by negative reward prediction error, to which a
      population of neurons in the orbitofrontal cortex responds. The representation in
      the orbitofrontal cortex but not the primary taste or olfactory cortex is of the
      reward value of the visual/olfactory/taste input as shown by devaluation
      experiments in which food is fed to satiety, and by correlations of the
      activations with subjective pleasantness ratings in humans. Sensory-specific
      satiety for taste, olfactory, visual, and oral somatosensory inputs produced by
      feeding a particular food to satiety is implemented it is proposed by medium-term
      synaptic adaptation in the orbitofrontal cortex. Cognitive factors, including
      word-level descriptions, modulate the representation of the reward value of food
      in the orbitofrontal cortex, and this effect is learned it is proposed by
      associative modification of top-down synapses onto neurons activated by bottom-up
      taste and olfactory inputs when both are active in the orbitofrontal cortex. A
      similar associative synaptic learning process is proposed to be part of the
      mechanism for the top-down attentional control to the reward value vs. the
      sensory properties such as intensity of taste and olfactory inputs in the
      orbitofrontal cortex, as part of a biased activation theory of selective
      attention.

PMID- 21954381
TI  - Differential Regulation of Neuropeptide Y in the Amygdala and Prefrontal Cortex
      during Recovery from Chronic Variable Stress.
AB  - Accumulating evidence from clinical studies and pre-clinical animal models
      supports a role for neuropeptide Y (NPY) in adaptive emotional response following
      stress. The long-term impact of stress, particularly chronic stress, on
      availability, and function of resilience factors such as NPY may be critical to
      understanding the etiology of stress-related psychopathology. In these studies,
      we examined expression of NPY during recovery from a chronic variable stress
      (CVS) model of repetitive trauma in rats. Due to the importance of amygdala and
      prefrontal cortex in regulating emotional responses, we predicted chronic changes
      in NPY expression could contribute to persistent behavioral deficits seen in this
      model. Consistent with the hypothesis, ELISA for NPY peptide identified a
      significant reduction in NPY at the delayed (7 days) recovery time-point.
      Interestingly, a significant increase in prefrontal NPY was observed at the same
      recovery time-point. The mRNA expression for NPY was not changed in the amygdala
      or PFC, although there was a modest but not statistically significant increase in
      NPY mRNA at the delayed recovery time-point in the prefrontal cortex. The
      observed changes in NPY expression are consistent with maladaptive coping and
      enhanced emotionality, due to the nature of NPY signaling within these respective
      regions, and the nature of reciprocal connections between amygdala and prefrontal
      cortex.

PMID- 21954382
TI  - Face-sensitive processes one hundred milliseconds after picture onset.
AB  - The human face is the most studied object category in visual neuroscience. In a
      quest for markers of face processing, event-related potential (ERP) studies have
      debated whether two peaks of activity - P1 and N170 - are category-selective.
      Whilst most studies have used photographs of unaltered images of faces, others
      have used cropped faces in an attempt to reduce the influence of features
      surrounding the "face-object" sensu stricto. However, results from studies
      comparing cropped faces with unaltered objects from other categories are
      inconsistent with results from studies comparing whole faces and objects. Here,
      we recorded ERPs elicited by full front views of faces and cars, either unaltered
      or cropped. We found that cropping artificially enhanced the N170 whereas it did
      not significantly modulate P1. In a second experiment, we compared faces and
      butterflies, either unaltered or cropped, matched for size and luminance across
      conditions, and within a narrow contrast bracket. Results of Experiment 2
      replicated the main findings of Experiment 1. We then used face-car morphs in a
      third experiment to manipulate the perceived face-likeness of stimuli (100% face,
      70% face and 30% car, 30% face and 70% car, or 100% car) and the N170 failed to
      differentiate between faces and cars. Critically, in all three experiments, P1
      amplitude was modulated in a face-sensitive fashion independent of cropping or
      morphing. Therefore, P1 is a reliable event sensitive to face processing as early
      as 100 ms after picture onset.

PMID- 21954383
TI  - An Ultrascalable Solution to Large-scale Neural Tissue Simulation.
AB  - Neural tissue simulation extends requirements and constraints of previous
      neuronal and neural circuit simulation methods, creating a tissue coordinate
      system. We have developed a novel tissue volume decomposition, and a hybrid
      branched cable equation solver. The decomposition divides the simulation into
      regular tissue blocks and distributes them on a parallel multithreaded machine.
      The solver computes neurons that have been divided arbitrarily across blocks. We
      demonstrate thread, strong, and weak scaling of our approach on a machine with
      more than 4000 nodes and up to four threads per node. Scaling synapses to
      physiological numbers had little effect on performance, since our decomposition
      approach generates synapses that are almost always computed locally. The largest
      simulation included in our scaling results comprised 1 million neurons, 1 billion
      compartments, and 10 billion conductance-based synapses and gap junctions. We
      discuss the implications of our ultrascalable Neural Tissue Simulator, and with
      our results estimate requirements for a simulation at the scale of a human brain.

PMID- 21954384
TI  - Temporal cognition: a key ingredient of intelligent systems.
AB  - Experiencing the flow of time is an important capacity of biological systems that
      is involved in many ways in the daily activities of humans and animals. However,
      in the field of robotics, the key role of time in cognition is not adequately
      considered in contemporary research, with artificial agents focusing mainly on
      the spatial extent of sensory information, almost always neglecting its temporal
      dimension. This fact significantly obstructs the development of high-level
      robotic cognitive skills, as well as the autonomous and seamless operation of
      artificial agents in human environments. Taking inspiration from biological
      cognition, the present work puts forward time perception as a vital capacity of
      artificial intelligent systems and contemplates the research path for
      incorporating temporal cognition in the repertoire of robotic skills.

PMID- 21954385
TI  - From the field into the lab: useful approaches to selecting species based on
      local knowledge.
AB  - Ethnopharmacological field studies are indispensable for identifying plants that
      can be selected for their pharmacological effects and chemical composition.
      Although the subjective interpretation of results by the researcher is crucial,
      quantitative data analysis is a useful tool to identify the most promising
      pharmacological plants. It has been stated that such semi-quantitative
      information increases the likelihood of finding promising ethnopharmacological
      leads, but so far no critical review has assessed what standards best meet the
      requirements of biomedical research. Systematic database searches using SCOPUS,
      Science Direct, Web of Knowledge, Science Citation Index, and Medline with the
      keywords "ethnobotany," "ethnopharmacology," "index," and "consensus" in research
      from the last 5 years form the basis of the current analysis, which identifies
      particularly useful tools like factor of informant consensus, fidelity level, use
      value, and relative importance. A key feature for further field studies is that
      they should provide clear information on a range of topics like; detailed data of
      the importance of these resources within a culture, data of the uses of the
      species, how and where the plants are collected, drying and storage processes,
      preparation method, used doses, and administration. In addition, they must
      include a collection of records about how the people feel after the plant use,
      disappearance of specific symptoms and possible side effects.

PMID- 21954386
TI  - Functional hemispheric specialization in processing phonemic and prosodic
      auditory changes in neonates.
AB  - This study focuses on the early cerebral base of speech perception by examining
      functional lateralization in neonates for processing segmental and suprasegmental
      features of speech. For this purpose, auditory evoked responses of full-term
      neonates to phonemic and prosodic contrasts were measured in their temporal area
      and part of the frontal and parietal areas using near-infrared spectroscopy
      (NIRS). Stimuli used here were phonemic contrast /itta/ and /itte/ and prosodic
      contrast of declarative and interrogative forms /itta/ and /itta?/. The results
      showed clear hemodynamic responses to both phonemic and prosodic changes in the
      temporal areas and part of the parietal and frontal regions. In particular,
      significantly higher hemoglobin (Hb) changes were observed for the prosodic
      change in the right temporal area than for that in the left one, whereas Hb
      responses to the vowel change were similarly elicited in bilateral temporal
      areas. However, Hb responses to the vowel contrast were asymmetrical in the
      parietal area (around supra marginal gyrus), with stronger activation in the
      left. These results suggest a specialized function of the right hemisphere in
      prosody processing, which is already present in neonates. The parietal activities
      during phonemic processing were discussed in relation to verbal-auditory short
      term memory. On the basis of this study and previous studies on older infants,
      the developmental process of functional lateralization from birth to 2 years of
      age for vowel and prosody was summarized.

PMID- 21954387
TI  - Abstract and concrete sentences, embodiment, and languages.
AB  - One of the main challenges of embodied theories is accounting for meanings of
      abstract words. The most common explanation is that abstract words, like concrete
      ones, are grounded in perception and action systems. According to other
      explanations, abstract words, differently from concrete ones, would activate
      situations and introspection; alternatively, they would be represented through
      metaphoric mapping. However, evidence provided so far pertains to specific
      domains. To be able to account for abstract words in their variety we argue it is
      necessary to take into account not only the fact that language is grounded in the
      sensorimotor system, but also that language represents a linguistic-social
      experience. To study abstractness as a continuum we combined a concrete (C) verb
      with both a concrete and an abstract (A) noun; and an abstract verb with the same
      nouns previously used (grasp vs. describe a flower vs. a concept). To
      disambiguate between the semantic meaning and the grammatical class of the words,
      we focused on two syntactically different languages: German and Italian.
      Compatible combinations (CC, AA) were processed faster than mixed ones (CA, AC).
      This is in line with the idea that abstract and concrete words are processed
      preferentially in parallel systems - abstract in the language system and concrete
      more in the motor system, thus costs of processing within one system are the
      lowest. This parallel processing takes place most probably within different
      anatomically predefined routes. With mixed combinations, when the concrete word
      preceded the abstract one (CA), participants were faster, regardless of the
      grammatical class and the spoken language. This is probably due to the peculiar
      mode of acquisition of abstract words, as they are acquired more linguistically
      than perceptually. Results confirm embodied theories which assign a crucial role
      to both perception-action and linguistic experience for abstract words.

PMID- 21954388
TI  - What's Cooking? - Cognitive Training of Executive Function in the Elderly.
AB  - Executive function involves the efficient and adaptive engagement of the control
      processes of updating, shifting, and inhibition (Miyake, 2000) to guide behavior
      toward a goal. It is associated with decrements in many other cognitive functions
      due to aging (West, 1996; Raz, 2000) with itself particularly vulnerable to the
      effect of aging (Treitz et al., 2007). Cognitive training in the form of
      structural experience with executive coordination demands exhibited effective
      enhancement in the elderly (Hertzog et al., 2008). The current study was thus
      aimed at the development and evaluation of a training regime for executive
      function in the elderly. The breakfast cooking task of Craik and Bialystok (2006)
      was adapted into a multitasking training task in a session (pre-test vs. post
      test) by group (control vs. training). In the training condition, participants
      constantly switched, updated, and planned in order to control the cooking of
      several foods and concurrently performed a table setting secondary task. Training
      gains were exhibited on task related measures. Transfer effect was selectively
      observed on the letter-number sequencing and digit symbol coding test. The
      cooking training produced short term increase in the efficiency of executive
      control processing. These effects were interpreted in terms of the process
      overlap between the training and the transfer tasks.

PMID- 21954389
TI  - Affective privilege: asymmetric interference by emotional distracters.
AB  - Numerous theories posit that affectively salient stimuli are privileged in their
      capacity to capture attention and disrupt ongoing cognition. Two underlying
      assumptions in this theoretical position are that the potency of affective
      stimuli transcends task boundaries (i.e., emotional distracters do not have to
      belong to a current task-set to disrupt processing) and that there is an
      asymmetry between emotional and cognitive processing (i.e., emotional distracters
      disrupt cognitive processing, but not vice versa). These assumptions have
      remained largely untested, as common experimental probes of emotion-cognition
      interaction rarely manipulate task-relevance and only examine one side of the
      presumed asymmetry of interference. To test these propositions directly, a face
      word Stroop protocol was adapted to independently manipulate (a) the congruency
      between target and distracter stimulus features, (b) the affective salience of
      distracter features, and (c) the task-relevance of emotional compared to non
      emotional target features. A three-way interaction revealed interdependent
      effects of distracter relevance, congruence, and affective salience. Compared to
      task-irrelevant distracters, task-relevant congruent distracters facilitated
      performance and task-relevant incongruent distracters impaired performance, but
      the latter effect depended on the nature of the target feature and task.
      Specifically, task-irrelevant emotional distracters resulted in equivalent
      performance costs as task-relevant non-emotional distracters, whereas task
      irrelevant non-emotional distracters did not produce performance costs comparable
      to those generated by task-relevant emotional distracters. These results document
      asymmetric cross-task interference effects for affectively salient stimuli,
      supporting the notion of affective prioritization in human information
      processing.

PMID- 21954391
TI  - Executive control of language in the bilingual brain: integrating the evidence
      from neuroimaging to neuropsychology.
AB  - In this review we will focus on delineating the neural substrates of the
      executive control of language in the bilingual brain, based on the existing
      neuroimaging, intracranial, transcranial magnetic stimulation, and
      neuropsychological evidence. We will also offer insights from ongoing brain
      imaging studies into the development of expertise in multilingual language
      control. We will concentrate specifically on evidence regarding how the brain
      selects and controls languages for comprehension and production. This question
      has been addressed in a number of ways and using various tasks, including
      language switching during production or perception, translation, and
      interpretation. We will attempt to synthesize existing evidence in order to bring
      to light the neural substrates that are crucial to executive control of language.

PMID- 21954390
TI  - Post-error adjustments.
AB  - When our brain detects an error, this process changes how we react on ensuing
      trials. People show post-error adaptations, potentially to improve their
      performance in the near future. At least three types of behavioral post-error
      adjustments have been observed. These are post-error slowing (PES), post-error
      reduction of interference, and post-error improvement in accuracy (PIA). Apart
      from these behavioral changes, post-error adaptations have also been observed on
      a neuronal level with functional magnetic resonance imaging and
      electroencephalography. Neuronal post-error adaptations comprise activity
      increase in task-relevant brain areas, activity decrease in distracter-encoding
      brain areas, activity modulations in the motor system, and mid-frontal theta
      power increases. Here, we review the current literature with respect to these
      post-error adjustments, discuss under which circumstances these adjustments can
      be observed, and whether the different types of adjustments are linked to each
      other. We also evaluate different approaches for explaining the functional role
      of PES. In addition, we report reanalyzed and follow-up data from a flanker task
      and a moving dots interference task showing (1) that PES and PIA are not
      necessarily correlated, (2) that PES depends on the response-stimulus interval,
      and (3) that PES is reliable on a within-subject level over periods as long as
      several months.

PMID- 21954392
TI  - A Generative Model of Speech Production in Broca's and Wernicke's Areas.
AB  - Speech production involves the generation of an auditory signal from the
      articulators and vocal tract. When the intended auditory signal does not match
      the produced sounds, subsequent articulatory commands can be adjusted to reduce
      the difference between the intended and produced sounds. This requires an
      internal model of the intended speech output that can be compared to the produced
      speech. The aim of this functional imaging study was to identify brain activation
      related to the internal model of speech production after activation related to
      vocalization, auditory feedback, and movement in the articulators had been
      controlled. There were four conditions: silent articulation of speech, non-speech
      mouth movements, finger tapping, and visual fixation. In the speech conditions,
      participants produced the mouth movements associated with the words "one" and
      "three." We eliminated auditory feedback from the spoken output by instructing
      participants to articulate these words without producing any sound. The non
      speech mouth movement conditions involved lip pursing and tongue protrusions to
      control for movement in the articulators. The main difference between our speech
      and non-speech mouth movement conditions is that prior experience producing
      speech sounds leads to the automatic and covert generation of auditory and
      phonological associations that may play a role in predicting auditory feedback.
      We found that, relative to non-speech mouth movements, silent speech activated
      Broca's area in the left dorsal pars opercularis and Wernicke's area in the left
      posterior superior temporal sulcus. We discuss these results in the context of a
      generative model of speech production and propose that Broca's and Wernicke's
      areas may be involved in predicting the speech output that follows articulation.
      These predictions could provide a mechanism by which rapid movement of the
      articulators is precisely matched to the intended speech outputs during future
      articulations.

PMID- 21954393
TI  - Embryonic amygdalar transplants in adult rats with motor cortex lesions: a
      molecular and electrophysiological analysis.
AB  - Transplants of embryonic nervous tissue ameliorate motor deficits induced by
      motor cortex lesions in adult animals. Restoration of lost brain functions has
      been recently shown in grafts of homotopic cortical origin, to be associated with
      a functional integration of the transplant after development of reciprocal host
      graft connections. Nevertheless little is known about physiological properties or
      gene expression profiles of cortical implants with functional restorative
      capacity but no cortical origin. In this study, we show molecular and
      electrophysiological evidence supporting the functional development and
      integration of heterotopic transplants of embryonic amygdalar tissue placed into
      pre-lesioned motor cortex of adult rats. Grafts were analyzed 3 months post
      transplantation. Using reverse transcriptase quantitative polymerase chain
      reaction, we found that key glutamatergic, GABAergic, and muscarinic receptors
      transcripts were expressed at different quantitative levels both in grafted and
      host tissues, but were all continuously present in the graft. Parallel sharp
      electrode recordings of grafted neurons in brain slices showed a regular firing
      pattern of transplanted neurons similar to host amygdalar pyramidal neurons.
      Synaptic connections from the adjacent host cortex on grafted neurons were
      electrophysiologically investigated and confirmed our molecular results. Taken
      together, our findings indicate that grafted neurons from a non-cortical, non
      motor-related, but ontogenetical similar source, not only received functionally
      effective contacts from the adjacent motor cortex, but also developed
      electrophysiological and gene expression patterns comparable to host pyramidal
      neurons; suggesting an interesting tool for the field of neural repair and donor
      tissue in adults.

PMID- 21954394
TI  - Cultivating uncultured bacteria from northern wetlands: knowledge gained and
      remaining gaps.
AB  - Northern wetlands play a key role in the global carbon budget, particularly in
      the budgets of the greenhouse gas methane. These ecosystems also determine the
      hydrology of northern rivers and represent one of the largest reservoirs of fresh
      water in the Northern Hemisphere. Sphagnum-dominated peat bogs and fens are the
      most extensive types of northern wetlands. In comparison to many other
      terrestrial ecosystems, the bacterial diversity in Sphagnum-dominated wetlands
      remains largely unexplored. As demonstrated by cultivation-independent studies, a
      large proportion of the indigenous microbial communities in these acidic, cold,
      nutrient-poor, and water-saturated environments is composed of as-yet
      uncultivated bacteria with unknown physiologies. Most of them are slow-growing,
      oligotrophic microorganisms that are difficult to isolate and to manipulate in
      the laboratory. Yet, significant breakthroughs in cultivation of these elusive
      organisms have been made during the last decade. This article describes the major
      prerequisites for successful cultivation of peat-inhabiting microbes, gives an
      overview of the currently captured bacterial diversity from northern wetlands and
      discusses the unique characteristics of the newly discovered organisms.

PMID- 21954396
TI  - Human health and disease in a microbial world.

PMID- 21954395
TI  - Mechanism and Function of the Outer Membrane Channel TolC in Multidrug Resistance
      and Physiology of Enterobacteria.
AB  - TolC is an archetypal member of the outer membrane efflux protein (OEP) family.
      These proteins are involved in export of small molecules and toxins across the
      outer membrane of Gram-negative bacteria. Genomes of some bacteria such as
      Pseudomonas species contain multiple copies of OEPs. In contrast, enterobacteria
      contain a single tolC gene, the product of which functions with multiple
      transporters. Inactivation of tolC has a major impact on enterobacterial
      physiology and virulence. Recent studies suggest that the role of TolC in
      physiology of enterobacteria is very broad and affects almost all aspects of cell
      adaptation to adverse environments. We review the current state of understanding
      TolC structure and present an integrated view of TolC function in enterobacteria.
      We propose that seemingly unrelated phenotypes of tolC mutants are linked
      together by a single most common condition - an oxidative damage to membranes.

PMID- 21954397
TI  - Salmonella host-pathogen interactions: a special topic.

PMID- 21954399
TI  - Locked knee?

PMID- 21954398
TI  - Innate Immune Responses to AAV Vectors.
AB  - Gene replacement therapy by in vivo delivery of adeno-associated virus (AAV) is
      attractive as a potential treatment for a variety of genetic disorders. However,
      while AAV has been used successfully in many models, other experiments in
      clinical trials and in animal models have been hampered by undesired responses
      from the immune system. Recent studies of AAV immunology have focused on the
      elimination of transgene-expressing cells by the adaptive immune system, yet the
      innate immune system also has a critical role, both in the initial response to
      the vector and in prompting a deleterious adaptive immune response. Responses to
      AAV vectors are primarily mediated by the TLR9-MyD88 pathway, which induces the
      production of pro-inflammatory cytokines by activating the NF-kappaB pathways and
      inducing type I IFN production; self-complementary AAV vectors enhance these
      inflammatory processes. Additionally, the alternative NF-kappaB pathway
      influences transgene expression in cells transduced by AAV. This review
      highlights these recent discoveries regarding innate immune responses to AAV and
      discusses strategies to ablate these potentially detrimental signaling pathways.

PMID- 21954400
TI  - Hip pain in pregnancy.

PMID- 21954401
TI  - A case of ventral hernia mesh migration with splenosis mimicking a gastric mass.
AB  - This case reports the presentation and investigation of a 64-year-old woman
      presenting with symptoms of bowel obstruction and found to have synchronous
      intraluminal migration of a polypropylene mesh from a ventral hernia repair and
      splenosis compressing the stomach wall. The use of synthetic mesh in any type of
      hernia repair has a number of risks, one of which is transmigration. This is a
      very rare complication but has been reported in a number of cases following both
      open and transabdominal pre-peritoneal repairs of inguinal hernias. Heterotopic
      splenic tissue or "splenosis" can be a cause of a soft tissue mass, which can
      mimic a neoplasm leading to misdiagnosis. These implants result from either
      splenic trauma or after splenic surgery.

PMID- 21954402
TI  - "Up yours": smuggling illicit drugs into prison.
AB  - A significant proportion of patients who are heroin-dependant and receiving
      treatment in the community serve prison sentences at some point in their lives,
      meaning their treatment continues "on the inside". Although prison inmates are
      promised the same quality of care as they would get "on the outside", this is not
      always the case. Some drawbacks of the drug treatments offered in prisons can
      lead to people smuggling drugs into prisons. The present work describes how a
      patient, who is heroin dependant and attending a community drug and alcohol team
      for methadone maintenance treatment, smuggled methadone and heroin into prison,
      his reasons for doing that, his personal description of the extent of drug use in
      prisons and finally what can be done to stop it from treatment and policy
      perspectives. Drug misuse is common in prisons. Much more can be done at
      treatment and policy levels to prevent people smuggling drugs into prison.

PMID- 21954403
TI  - Histoplasma capsulatum in peripheral blood smear.

PMID- 21954404
TI  - Cerebral single photon emission computer tomography in thalamic lacunar
      infarction presenting with amnesia.

PMID- 21954405
TI  - Chest wall swelling: unusual presentation of an aggressive mediastinal tumour.
AB  - The majority of patients with primary mediastinal lymphoma are symptomatic at the
      time of diagnosis and commonly have fever, weight loss and/or night sweats.
      Symptoms due to compression of adjacent mediastinal structures are infrequent,
      but may include pain, dyspnoea, stridor, or superior vena cava syndrome. Local
      infiltration into the chest wall, pleura and pericardium is not uncommon.In the
      present report, two interesting cases of chest wall swellings that in fact were
      extensions of primary mediastinal lymphoma are given. Histopathology of the
      tumour was large B cell lymphoma (CD20+). The first case was in a 23-year-old
      woman, with dramatic onset but a good outcome. The second was in a 34-year-old
      Pakistani woman, with insidious onset and poor outcome due to extent and invasion
      by the tumour. Interesting CT images are presented showing chest wall and left
      supraclavicular swelling.

PMID- 21954406
TI  - Postoperative nausea and vomiting in a gynecological and obstetrical population
      in South Eastern Nigeria.
AB  - BACKGROUND: To determine the incidence of Postoperative nausea and vomiting
      (PONV) in a high risk surgical group following studies in other predominately
      black populations that showed a lower rate of postoperative nausea and vomiting
      than that reported from Caucasian and Oriental populations. METHODS: A
      retrospective observational survey was conducted in the University of Nigeria
      Teaching Hospital (UNTH), Enugu, Nigeria to determine the incidence of PONV
      within forty-eight hours of anesthesia in an obstetrical (caesarean sections
      only) and gynecological population that underwent regional and general
      anesthesia. The study took place from December 2007-April 2009 (16 months) for
      the gynecological population and from May 2008 to May 2010 (25 months) for the
      obstetrical population. The folders of 300 patients were randomly reviewed for
      demographics, anesthetic technique, diagnosis and documented records of PONV
      within 48 hours of anesthesia. RESULTS: A total of 300 obstetrical and
      gynecological patients were used in this study. Twelve women vomited within forty
      eight hours of anesthesia (12/300 or 4.0%). Nine patients vomited in the
      gynecological population (9/112) or 8% of the gynecological population and
      (3/186) or 1.6% in the obstetric population. All patients were American Society
      of Anesthesiologists (ASA) 1-4 including surgical emergencies. CONCLUSION: The
      incidence of PONV in this surgical population is lower than that from most of the
      studies reviewed. This might be due to an inherent ethnic/racial variation. The
      economic implication of spending on expensive anti-emetics means more money can
      diverted to other needs.

PMID- 21954407
TI  - [Colonic atresia: report of two cases].

PMID- 21954408
TI  - Corticosteroids and pentoxifylline for the treatment of alcoholic hepatitis:
      Current status.
AB  - The treatment of choice for patients with severe alcoholic hepatitis (AH) is use
      of corticosteroids. Many randomized well designed studies have been reported from
      all over the world on the use of corticosteroids in the treatment of AH. However,
      the data on the efficacy of corticosteroids in these patients have been
      conflicting. Initial meta-analyses also failed to show beneficial effects of
      corticosteroids. Based on individual data meta-analysis showing clear benefit of
      corticosteroids amongst patients with severe AH (modified discriminant function
      of 32 or more), led American College of Gastroenterology to recommend use of
      corticosteroids as the first line treatment option amongst patients with severe
      AH. However, corticosteroids are relatively contraindicated amongst patients with
      severe AH and coexistent sepsis, gastrointestinal bleeding, and acute
      pancreatitis. These patients may be candidates for second line treatment with
      pentoxifylline. Further, specific treatment of AH with corticosteroids far from
      satisfactory with as many as 40%-50% of patients failing to respond to steroids,
      thus classified as non-responsive to steroids. The management of these patients
      is a continuing challenge for physicians. Better treatment modalities need to be
      developed for this group of patients in order to improve the outcome of patients
      with severe AH. This article describes at length the available trials on use of
      corticosteroids and pentoxifylline with their current status. Route of
      administration, dosage, adverse effects, and mechanisms of action of these two
      drugs are also discussed. Finally, an algorithm with clinical approach to
      management of patients who present with clinical syndrome of AH is described.

PMID- 21954409
TI  - Recent and currently emerging medical treatment options for the treatment of
      alcoholic hepatitis.
AB  - Patients with severe alcoholic hepatitis (AH) need to be treated with specific
      treatment for better outcome. Currently available specific treatment modalities
      are use of corticosteroids or pentoxifylline. However, the response rate to these
      drugs is only about 50%-60%. Hence, there is an urgent need for better and more
      effective treatment options. Tumor necrosis factor plays an important role in the
      pathogenesis of AH. However, agents blocking the action of tumor necrosis factor
      have not been found to be effective. Rather the randomized studies evaluating
      these agents showed an adverse effect and more infections in treated patients.
      Critical role of tumor necrosis factor in hepatic regeneration explaining this
      contrast is discussed. Oxidative stress and inflammation derived from gut
      bacteria ate two main components in the pathogenesis of AH laying foundation for
      the role of antioxidants, probiotics, and antibiotics in the management of AH.
      This article reviews the current data and status of these newer agents for the
      treatment of AH. Of the various options available, Vitamin E and N-acetylcysteine
      (NAC) have shown great promise for clinical use as adjunct to corticosteroids.
      With these encouraging data, future well designed studies are suggested to assess
      Vitamin E and NAC before their routine use in clinical practice in the management
      of AH.

PMID- 21954410
TI  - Liver transplantation in acute alcoholic hepatitis: Current status and future
      development.
AB  - Acute alcoholic hepatitis (AH) is a distinct clinical entity amongst patients
      with chronic alcohol abuse. Patients with severe AH are at risk of dying in about
      20%-25% cases despite specific treatment with corticosteroids and/or
      pentoxifylline. Clearly, a need for an additional more effective treatment option
      is unmet currently. Liver transplantation (LT), a definitive treatment option for
      alcoholic cirrhosis requires 6 mo abstinence. However, this rule cannot be
      applied to patients with AH as these patients are actively drinking prior to
      their presentation. Shortage of donors, ethical issues, and fear of recidivism
      after transplantation with less than 6 mo pre-transplant abstinence are some of
      the reasons behind this rule of 6 mo of abstinence and hesitancy of transplanting
      patients with AH. These issues are debated at length in this manuscript. Further,
      retrospective studies have shown that patients undergoing transplantation for
      alcoholic cirrhosis and having histological changes of AH have been shown to fare
      as well when compared to patients without these histological changes. Recently,
      French workers have reported a case matched prospective study showing encouraging
      data on the usefulness of LT for patients who are non-responders to
      corticosteroid and/or pentoxifylline therapy. Future studies are needed to
      identify patients with severe AH who are going to benefit most with LT. In the
      light of emerging data on the efficacy of LT in improving survival of patients
      with severe acute AH who do not respond to corticosteroids, the time is ripe to
      re-evaluate our policy of LT in patients with AH.

PMID- 21954412
TI  - Endoscopic and histopathological features of gastrointestinal amyloidosis.
AB  - Amyloidosis is a rare disorder, characterized by the extracellular deposition of
      an abnormal fibrillar protein, which disrupts tissue structure and function.
      Amyloidosis can be acquired or hereditary, and systemic or localized to a single
      organ, such as the gastrointestinal (GI) tract. Clinical manifestations may vary
      from asymptomatic to fatal forms. Primary amyloidosis (monoclonal immunoglobulin
      light chains, AL) is the most common form of amyloidosis. AL amyloidosis has been
      associated with plasma cell dyscrasias, such as, multiple myeloma. Secondary
      amyloidosis is caused by the deposition of fragments of the circulating acute
      phase reactant, serum amyloid A protein (SAA). Common causes of AA amyloidosis
      are chronic inflammatory disorders. Although GI symptoms are usually nonspecific,
      histopathological patterns of amyloid deposition are associated with clinical and
      endoscopic features. Amyloid deposition in the muscularis mucosae, submucosa, and
      muscularis propria has been dominant in AL amyloidosis, leading to polypoid
      protrusions and thickening of the valvulae conniventes, whereas granular amyloid
      deposition mainly in the propria mucosae has been related to AA amyloidosis,
      resulting in the fine granular appearance, mucosal friability, and erosions. As a
      result, AL amyloidosis usually presents with constipation, mechanical
      obstruction, or chronic intestinal pseudo-obstruction while AA amyloidosis
      presents with diarrhea and malabsorption Amyloidotic GI symptoms are mostly
      refractory and have a negative impact on quality of life and survival. Diagnosing
      GI amyloidosis requires high suspicion of evaluating endoscopists. Because of the
      absence of specific treatments for reducing the abundance of the amyloidogenic
      precursor protein, we should be aware of certain associations between patterns of
      amyloid deposition and clinical and endoscopic features.

PMID- 21954411
TI  - Noninvasive predictors for liver fibrosis in patients with nonalcoholic
      steatohepatitis.
AB  - AIM: To evaluate certain anthropometric, clinical and laboratory features
      indicating liver fibrosis in nonalcoholic steatohepatitis and to establish the
      noninvasive markers for liver fibrosis. METHODS: Eighty-one patients (40 male, 41
      female) who were diagnosed with fatty liver by ultrasonographic examination and
      fulfilled the inclusion criteria participated in the study. Anamnesis,
      anthropometric, clinical and laboratory features of all cases were recorded and
      then liver biopsy was performed after obtaining patient consent. Steatosis,
      necroinflammation and liver fibrosis were examined according to age >= 45,
      gender, body mass index, central obesity, aspartate aminotransferase
      (AST)/alanine aminotransferase (ALT) > 1, gamma-glutamyltransferase (GGT)/ALT >
      1, platelet count, insulin, c-peptide levels and the presence of hypertension,
      diabetes, hypertriglyceridemia and insulin resistance. RESULTS: Eighty-one
      patients with non-alcoholic steatohepatitis (NASH) enrolled in the study. 69 of
      81 patients were diagnosed with NASH, 11 were diagnosed with simple fatty liver
      and 1 was diagnosed with cirrhosis. AST/ALT > 1, GGT/ALT > 11, high serum
      ferritin and fasting insulin levels, the presence of diabetes, hypertension,
      hypertriglyceridemia and insulin resistance seemed to enhance the severity of
      steatosis, necroinflammation and fibrosis but these results were not
      statistically significant. CONCLUSION: Liver steatosis and fibrosis can occur in
      individuals with normal weight. There was no significant concordance between
      severity of liver histology and the presence of predictors for liver fibrosis
      including metabolic risk factors.

PMID- 21954413
TI  - Transnasal and standard transoral endoscopies in the screening of gastric mucosal
      neoplasias.
AB  - AIM: To compare the diagnostic performances of transnasal and standard transoral
      esophagogastroduodenoscopy (EGD) in gastric cancer screening of asymptomatic
      healthy subjects. METHODS: Between January 2006 and March 2010, a total of 3324
      subjects underwent examination of the upper gastrointestinal tract by EGD for
      cancer screening, with 1382 subjects (41.6%) screened by transnasal EGD and the
      remaining 1942 subjects (58.4%) by standard transoral EGD. Clinical profiles of
      the screened subjects, detection rates of gastric neoplasia and histopathology of
      the detected neoplasias were compared between groups according to the stage of
      Helicobacter pylori(H. pylori)-related chronic gastritis. RESULTS: Clinical
      profiles of subjects did not differ significantly between the two EGD groups,
      except that there were significantly more men in the transnasal EGD group. During
      the study period, 55 cases of gastric mucosal neoplasias were detected. Of these,
      23 cases were detected by transnasal EGD and 32 cases by standard transoral EGD.
      The detection rate for gastric mucosal neoplasia in the transnasal EGD group was
      thus 1.66%, compared to 1.65% in the standard transoral EGD group, with no
      significant difference between the two groups. Detection rates using the two
      endoscopies were likewise comparable, regardless of H. pylori infection. However,
      detection rates when screening subjects without extensive chronic atrophic
      gastritis (CAG) were significantly higher with standard transoral EGD (0.70%)
      than with transnasal EGD (0.12%, P < 0.05). In particular, standard transoral EGD
      was far better for detecting neoplasia in subjects with H. pylori-related non
      atrophic gastritis, with a detection rate of 3.11% compared to 0.53% using
      transnasal EGD (P < 0.05). In the screening of subjects with extensive CAG, no
      significant differences in detection of neoplasia were evident between the two
      endoscopies, although the mean size of detected cancers was significantly smaller
      and the percentage of early cancers was significantly higher with standard
      transoral EGD. CONCLUSION: These results strongly suggest that the diagnostic
      performance of transnasal endoscopy is suboptimal for cancer screening,
      particularly in subjects with H. pylori-related non-atrophic gastritis.

PMID- 21954414
TI  - Endoscopic resection techniques and ablative therapies for Barrett's neoplasia.
AB  - Esophageal adenocarcinoma is the most rapidly increasing cancer in western
      countries. High-grade dysplasia (HGD) arising from Barrett's esophagus (BE) is
      the most important risk factor for its development, and when it is present the
      reported incidence is up to 10% per patient-year. Adenocarcinoma in the setting
      of BE develops through a well known histological sequence, from non-dysplastic
      Barrett's to low grade dysplasia and then HGD and cancer. Endoscopic surveillance
      programs have been established to detect the presence of neoplasia at a
      potentially curative stage. Newly developed endoscopic treatments have
      dramatically changed the therapeutic approach of BE. When neoplasia is confined
      to the mucosal layer the risk for developing lymph node metastasis is negligible
      and can be successfully eradicated by an endoscopic approach, offering a curative
      intention treatment with minimal invasiveness. Endoscopic therapies include
      resection techniques, also known as tissue-acquiring modalities, and ablation
      therapies or non-tissue acquiring modalities. The aim of endoscopic treatment is
      to eradicate the whole Barrett's segment, since the risk of developing
      synchronous and metachronous lesions due to the persistence of molecular
      aberrations in the residual epithelium is well established.

PMID- 21954415
TI  - Nutritional programming of pancreatic beta-cell plasticity.
AB  - Nutritional insufficiency during pregnancy has been shown to alter the metabolism
      of the offspring and can increase the risk of type 2 diabetes. The phenotype in
      the offspring involves changes to the morphology and functional capacity of the
      endocrine pancreas, and in the supporting islet microvasculature. Pancreatic beta
      cells possess a plastic potential and can partially recover from catastrophic
      loss. This is partly due to the existence of progenitors within the islets and
      the ability to generate new islets by neogenesis from the pancreatic ducts. This
      regenerative capacity is induced by bone marrow-derived stem cells, including
      endothelial cell progenitors and is associated with increased angiogenesis within
      the islets. Nutritional insults in early life, such as feeding a low protein diet
      to the mother, impair the regenerative capacity of the beta-cells. The mechanisms
      underlying this include a reduced ability of beta-cells to differentiate from the
      progenitor population, changes in the inductive signals from the microvasculature
      and an altered presence of endothelial progenitors. Statin treatment within
      animal models was associated with angiogenesis in the islet microvasculature,
      improved vascular function and an increase in beta-cell mass. This demonstrates
      that reversal of the impaired beta-cell phenotype observed following nutritional
      insult in early life is potentially possible.

PMID- 21954416
TI  - Mechanisms behind early life nutrition and adult disease outcome.
AB  - Obesity is increasing around the globe. While adult lifestyle factors undoubtedly
      contribute to the incidence of obesity and its attendant disorders, mounting
      evidence suggests that programming of obesity may occur following under- and over
      nutrition during development. As hypothalamic control of appetite and energy
      expenditure is set early in life and can be perturbed by certain exposures such
      as undernutrition and altered metabolic and hormonal signals, in utero exposure
      to altered maternal nutrition and inadequate nutrition during early postnatal
      life may contribute to programming of obesity in offspring. Data from animal
      studies indicate both intrauterine and postnatal environments are critical
      determinants of the development of pathways regulating energy homeostasis. This
      review summarizes recent evidence of the impact of maternal nutrition as well as
      postnatal nutrition of the offspring on subsequent obesity and disease risk of
      the offspring. While much of the experimental work reviewed here was conducted in
      the rodent, these observations provide useful insights into avenues for future
      research into developing preventive measures to curb the obesity epidemic.

PMID- 21954417
TI  - Perinatal nutritional programming of health and metabolic adult disease.
AB  - Data indicate that perinatal nutritional insults not onlyhave short-term
      consequences on the growth velocity of the fetus/neonate but also sensitize to
      the development of metabolic adult diseases. The pathophysiological mechanisms
      involved in the so-called "Developmental Origin of Health and Adult Diseases" are
      still largely unknown and depend on the type of alteration (nutritional,
      psychological, endocrine disruptors, etc.), its intensity and duration, species,
      sex and the time during which it is applied. Perinatal stress, via disturbances
      of both hypothalamo-pituitary-adrenal (HPA) axis and sympatho-adrenal-system
      (SAS), as well as brain-adipose axis and pancreas alterations could play a
      crucial role. Interestingly, it has been demonstrated that perinatal insults may
      be transmitted transgenerationally, suggesting that these long-term consequences
      may be inherited via epigenetic mechanisms. Finally, since the placenta has been
      demonstrated to be sensitive to perinatal nutritional manipulations, the
      identification of placental markers may thus represent an important new avenue to
      identify the more susceptible babies prone to developing metabolic diseases.

PMID- 21954420
TI  - The road less traveled.

PMID- 21954418
TI  - Developmental programming of the metabolic syndrome - critical windows for
      intervention.
AB  - Metabolic disease results from a complex interaction of many factors, including
      genetic, physiological, behavioral and environmental influences. The recent rate
      at which these diseases have increased suggests that environmental and behavioral
      influences, rather than genetic causes, are fuelling the present epidemic. In
      this context, the developmental origins of health and disease hypothesis has
      highlighted the link between the periconceptual, fetal and early infant phases of
      life and the subsequent development of adult obesity and the metabolic syndrome.
      Although the mechanisms are yet to be fully elucidated, this programming was
      generally considered an irreversible change in developmental trajectory. Recent
      work in animal models suggests that developmental programming of metabolic
      disorders is potentially reversible by nutritional or targeted therapeutic
      interventions during the period of developmental plasticity. This review will
      discuss critical windows of developmental plasticity and possible avenues to
      ameliorate the development of postnatal metabolic disorders following an adverse
      early life environment.

PMID- 21954419
TI  - Alteration of mitochondrial function in adult rat offspring of malnourished dams.
AB  - Under-nutrition as well as over-nutrition during pregnancy has been associated
      with the development of adult diseases such as diabetes and obesity. Both
      epigenetic modifications and programming of the mitochondrial function have been
      recently proposed to explain how altered intrauterine metabolic environment may
      produce such a phenotype. This review aims to report data reported in several
      animal models of fetal malnutrition due to maternal low protein or low calorie
      diet, high fat diet as well as reduction in placental blood flow. We focus our
      overview on the beta cell. We highlight that, notwithstanding early nutritional
      events, mitochondrial dysfunctions resulting from different alteration by diet or
      gender are programmed. This may explain the higher propensity to develop obesity
      and diabetes in later life.

PMID- 21954421
TI  - Gene expression pattern during osteogenic differentiation of human periodontal
      ligament cells in vitro.
AB  - PURPOSE: Periodontal ligament (PDL) cell differentiation into osteoblasts is
      important in bone formation. Bone formation is a complex biological process and
      involves several tightly regulated gene expression patterns of bone-related
      proteins. The expression patterns of bone related proteins are regulated in a
      temporal manner both in vivo and in vitro. The aim of this study was to observe
      the gene expression profile in PDL cell proliferation, differentiation, and
      mineralization in vitro. METHODS: PDL cells were grown until confluence, which
      were then designated as day 0, and nodule formation was induced by the addition
      of 50 ug/mL ascorbic acid, 10 mM beta-glycerophosphate, and 100 nM dexamethasone
      to the medium. The dishes were stained with Alizarin Red S on days 1, 7, 14, and
      21. Real-time polymerase chain reaction was performed for the detection of
      various genes on days 0, 1, 7, 14, and 21. RESULTS: On day 0 with a confluent
      monolayer, in the active proliferative stage, c-myc gene expression was observed
      at its maximal level. On day 7 with a multilayer, alkaline phosphatase, bone
      morphogenetic protein (BMP)-2, and BMP-4 gene expression had increased and this
      was followed by maximal expression of osteocalcin on day 14 with the initiation
      of nodule mineralization. In relationship to apoptosis, c-fos gene expression
      peaked on day 21 and was characterized by the post-mineralization stage. Here,
      various genes were regulated in a temporal manner during PDL fibroblast
      proliferation, extracellular matrix maturation, and mineralization. The gene
      expression pattern was similar. CONCLUSIONS: We can speculate that the gene
      expression pattern occurs during PDL cell proliferation, differentiation, and
      mineralization. On the basis of these results, it might be possible to understand
      the various factors that influence PDL cell proliferation, extracellular matrix
      maturation, and mineralization with regard to gene expression patterns.

PMID- 21954422
TI  - Dimensional change of the healed periosteum on surgically created defects.
AB  - PURPOSE: The final goal of regenerative periodontal therapy is to restore the
      structure and function of the periodontium destroyed or lost due to
      periodontitis. However, the role of periosteum in periodontal regeneration was
      relatively neglected while bone repair in the skeleton occurs as a result of a
      significant contribution from the periosteum. The aim of this study is to
      understand the histological characteristics of periosteum and compare the native
      periosteum with the repaired periosteum after elevating flap or after surgical
      intervention with flap elevation. METHODS: Buccal and lingual mucoperiosteal
      flaps were reflected to surgically create critical-size, "box-type" (4 mm width,
      5 mm depth), one-wall, intrabony defects at the distal aspect of the 2nd and the
      mesial aspect of the 4th mandibular premolars in the right and left jaw
      quadrants. Animals were sacrificed after 24 weeks. RESULTS: THE RESULTS FROM THIS
      STUDY ARE AS FOLLOWS: 1) thickness of periosteum showed difference as follows
      (P<0.05): control group (0.45+/-0.22 mm)>flap-elevation group (0.36+/-0.07
      mm)>defect formation group (0.26+/-0.03 mm), 2) thickness of gingival tissue
      showed difference as follows (P<0.05): defect formation group (3.15+/-0.40
      mm)>flap-elevation group (2.02+/-0.25 mm)>control group (1.88+/-0.27 mm), 3)
      higher cellular activity was observed in defect formation group and flap
      elevation groups than control group, 4) the number of blood vessles was higher in
      defect formation group than control group. CONCLUSIONS: In conclusion, prolonged
      operation with increased surgical trauma seems to decrease the thickness of
      repaired periosteum and increase the thickness of gingiva. More blood vessles and
      high cellular activity were observed in defect formation group.

PMID- 21954423
TI  - Tissue reactions to suture materials in the oral mucosa of beagle dogs.
AB  - PURPOSE: The objective of this study was to compare and evaluate the inflammatory
      responses of three widely used suture materials in the keratinized gingiva and
      buccal mucosa of beagle dogs. METHODS: Silk, polyglycolic acid, and nylon sutures
      were placed within the mandibular keratinized gingiva and maxillary buccal mucosa
      of four male beagle dogs. Biopsies were taken 3, 7, and 14 days after suturing.
      Specimens were prepared with hematoxylin-eosin stain for evaluation under a light
      microscope. RESULTS: The suture materials placed in the oral mucosa elicited more
      inflammatory reactions than did those placed in the keratinized gingiva. The
      multifilament suture materials caused more inflammatory tissue reactions than did
      the monofilament suture materials in the oral mucosa. CONCLUSIONS: If oral
      hygiene is well maintained and suture materials are placed in the keratinized
      gingiva, silk, nylon, and polyglycolic acid are considered to be proper suture
      materials for oral surgery. However, it is advisable to use monofilament suture
      materials if the suture site is within the oral mucosa.

PMID- 21954424
TI  - Gene expression profile in mesenchymal stem cells derived from dental tissues and
      bone marrow.
AB  - PURPOSE: The aim of this study is to compare the gene expression profile in
      mesenchymal stem cells derived from dental tissues and bone marrow for
      characterization of dental stem cells. METHODS: We employed GeneChip analysis to
      the expression levels of approximately 32,321 kinds of transcripts in 5 samples
      of bone-marrow-derived mesenchymal stem cells (BMSCs) (n=1), periodontal ligament
      stem cells (PDLSCs) (n=2), and dental pulp stem cells (DPSCs) (n=2). Each cell
      was sorted by a FACS Vantage Sorter using immunocytochemical staining of the
      early mesenchymal stem cell surface marker STRO-1 before the microarray analysis.
      RESULTS: We identified 379 up-regulated and 133 down-regulated transcripts in
      BMSCs, 68 up-regulated and 64 down-regulated transcripts in PDLSCs, and 218 up
      regulated and 231 down-regulated transcripts in DPSCs. In addition, anatomical
      structure development and anatomical structure morphogenesis gene ontology (GO)
      terms were over-represented in all three different mesenchymal stem cells and GO
      terms related to blood vessels, and neurons were over-represented only in DPSCs.
      CONCLUSIONS: This study demonstrated the genome-wide gene expression patterns of
      STRO-1(+) mesenchymal stem cells derived from dental tissues and bone marrow. The
      differences among the expression profiles of BMSCs, PDLSCs, and DPSCs were shown,
      and 999 candidate genes were found to be definitely up- or down-regulated. In
      addition, GOstat analyses of regulated gene products provided over-represented GO
      classes. These data provide a first step for discovering molecules key to the
      characteristics of dental stem cells.

PMID- 21954425
TI  - A comparison of different gingival depigmentation techniques: ablation by
      erbium:yttrium-aluminum-garnet laser and abrasion by rotary instruments.
AB  - PURPOSE: The aim of this study is to compare two different gingival
      depigmentation techniques using an erbium:yttrium-aluminum-garnet (Er:YAG) laser
      and rotary instruments. METHODS: Two patients with melanin pigmentation of
      gingiva were treated with different gingival depigmentation techniques. Ablation
      of the gingiva by Er:YAG laser was performed on the right side, and abrasion with
      a rotary round bur on the opposite side. RESULTS: The patients were satisfied
      with the esthetically significant improvement with each method. However, some
      pigment still remained on the marginal gingival and papilla. The visual analog
      scale did not yield much difference between the two methods, with slightly more
      pain on the Er:YAG laser treated site. CONCLUSIONS: The results of these cases
      suggest that ablation of the gingiva by an Er:YAG laser and abrasion with a
      rotary round bur is good enough to achieve esthetic satisfaction and fair wound
      healing without infection or severe pain. Prudent care about the gingival
      condition, such as the gingival thickness and degree of pigmentation along with
      appropriate assessment is needed in ablation by the Er:YAG laser procedure.

PMID- 21954426
TI  - Chronic daily headache, medication overuse, and obesity in children and
      adolescents.
AB  - Obesity and headaches are common in children and adults. Adult studies suggest
      obesity is a risk factor for chronic daily headache and increased migraine
      frequency and severity. Pediatric studies have suggested a relationship between
      obesity, increasing headache frequency, and disability. The authors
      retrospectively evaluated 925 children from their Pediatric Headache Clinic
      between July 2004 and July 2008, assessing headache frequency, medication
      overuse, and body mass index compared to population-based norms. The pediatric
      headache group as a whole had a greater percentage of overweight than the general
      population. This was also true with the subgroup of patients with chronic tension
      type headache, although the numbers were small. Data did not show increased
      incidence of overweight in children with medication overuse or chronic migraine.
      This contrasts with adult data, which have suggested a closer link between
      chronic migraine and obesity and have not supported a link with chronic tension
      type headache.

PMID- 21954427
TI  - A national profile of health care and family impacts of children with muscular
      dystrophy and special health care needs in the United States.
AB  - We used the 2005-2006 National Survey of Children with Special Health Care Needs
      to compare 3 types of outcomes between children with and those without parental
      reported muscular dystrophy: (1) functional limitations; (2) health care
      experiences in terms of the 5 components of a medical home; and (3) family
      impacts, including financial or out-of-pocket costs and parental employment and
      time use. We used weighted logistic regression to examine their associations with
      muscular dystrophy after adjustment for socio-demographic characteristics. Among
      children with special health care needs, children with reported muscular
      dystrophy were much more likely to have difficulties with ambulation and self
      care. They were more likely to have family members who reported financial
      problems, reduced or stopped employment, and spent more than 10 hours weekly
      providing or coordinating care. Muscular dystrophy was not associated with the
      likelihood of having a medical home after adjustment for socioeconomic status and
      other socio-demographic characteristics.

PMID- 21954428
TI  - Urine phenobarbital drug screening: potential use for compliance assessment in
      neonates.
AB  - This study was done to determine if urine phenobarbital measurements provide a
      reliable indicator of presence of the drug in neonates. Urine was collected from
      neonates treated with phenobarbital for clinical indications within 4 to 6 hours
      of clinically indicated collection of serum phenobarbital levels. Urine samples
      were also collected from control neonates not treated with phenobarbital. One
      aliquot was assayed fresh, another frozen at -30 degrees C and assayed 1 to 3
      months later. Phenobarbital was assayed using the ONLINE TDM Roche/Hitachi
      automated clinical chemistry analyzer. Serum and urine concentrations were
      compared as were fresh and frozen urine measurements. Serum phenobarbital ranged
      from 5.6 to 52.7 MUg/mL. Matched urine samples were 56.6 +/- 12.5% of the serum
      level. Frozen samples were 98.3 +/- 8.0% of the fresh samples. Urine
      phenobarbital concentrations, either fresh or frozen, can be used in neonates as
      a noninvasive estimate of drug levels.

PMID- 21954429
TI  - The natural history of infant spinal muscular atrophy in China: a study of 237
      patients.
AB  - The authors retrospectively studied the natural history of 237 patients with
      infantile spinal muscular atrophy in China. The onset ages (mean +/- SD) for
      types I to III were 3.1 +/- 2.7, 8.7 +/- 3.8, and 21.1 +/- 11.7 months,
      respectively. The survival probabilities for type I patients at 1, 2, and 5 years
      were 44.9%, 38.1%, and 29.3%, respectively, and for type II patients, the
      probabilities were 100%, 100%, and 97%, respectively. All type III patients were
      alive. Type I patients with onset age after 2 months had significantly increased
      survival than those with onset before 2 months (P < .05). It should be noticed
      that survival probability at 2 years in type I patients in our study was close to
      that in other Asian samples of spinal muscular atrophy, but slightly better than
      that among whites. Patients accepted minimal proactive interventions other than
      antibiotics for pulmonary infection, so our study provides reliable baseline data
      of natural history of spinal muscular atrophy in China.

PMID- 21954430
TI  - The fetal cerebellum: development and common malformations.
AB  - The cerebellum undergoes a protracted development, making it particularly
      vulnerable to a broad spectrum of developmental events. Acquired destructive and
      hemorrhagic insults may also occur. The main steps of cerebellar development are
      reviewed. The normal imaging patterns of the cerebellum in prenatal ultrasound
      and magnetic resonance imaging (MRI) are described with emphasis on the
      limitations of these modalities. Because of confusion in the literature regarding
      the terminology used for cerebellar malformations, some terms (agenesis,
      hypoplasia, dysplasia, and atrophy) are clarified. Three main pathologic settings
      are considered and the main diagnoses that can be suggested are described:
      retrocerebellar fluid enlargement with normal or abnormal biometry (Dandy-Walker
      malformation, Blake pouch cyst, vermian agenesis), partially or globally
      decreased cerebellar biometry (cerebellar hypoplasia, agenesis,
      rhombencephalosynapsis, ischemic and/or hemorrhagic damage), partially or
      globally abnormal cerebellar echogenicity (ischemic and/or hemorrhagic damage,
      cerebellar dysplasia, capillary telangiectasia). The appropriate timing for
      performing MRI is also discussed.

PMID- 21954431
TI  - Copy number variations in patients with electrical status epilepticus in sleep.
AB  - Electrical status epilepticus in sleep syndrome is the association of the
      electroencephalographic pattern and deficits in language or global cognitive
      function and behavioral problems. The etiology is often unknown, but genetic risk
      factors have been implicated. Array-based comparative genomic hybridization was
      used to identify copy number variations in 13 children with electrical status
      epilepticus in sleep syndrome to identify possible underlying risk factors. Seven
      copy number variations were detected in 4 of the 13 patients, which consisted of
      6 novel gains and 1 loss, the recurrent 15q13.3 microdeletion. Two patients
      carried a probable pathogenic copy number variation containing a gene involved in
      the cholinergic pathway. Genetic aberrations in patients with electrical status
      epilepticus in sleep syndrome can provide an entry in the investigation of the
      etiology of electrical status epilepticus in sleep. However, further studies are
      needed to confirm our findings.

PMID- 21954433
TI  - Unexpected good motor and cognitive function in an extremely premature child with
      a history of perinatal cerebellar hemispheric infarction and multiple other risk
      factors for poor outcome.
AB  - Cerebellar infarction is a known possible complication of extreme prematurity,
      and usually results in severe disability. This report presents a 20-month-old
      girl (16 months corrected), who was born in a toilet at 24 weeks gestational age.
      She had multiple neonatal predictors of poor outcome, including unilateral
      cerebellar hemispheric infarction, grade 3 intraventricular hemorrhage,
      periventricular leukomalacia, fungal sepsis, patent ductus arteriosus, pulmonary
      valve stenosis, lack of prenatal care, and poor social situation. Despite all
      these poor prognostic factors, she was close to meeting corrected-age-appropriate
      motor and cognitive milestones. The etiology and outcomes of cerebellar
      infarction in extremely premature neonates, and possible contributors to this
      child's function, are discussed.

PMID- 21954432
TI  - The relationship of age, gender, and IQ with the brainstem and thalamus in
      healthy children and adolescents: a magnetic resonance imaging volumetric study.
AB  - In healthy children, there is a paucity of information on the growth of the
      brainstem and thalamus measured anatomically magnetic resonance imaging. The
      relations of age, gender, and age by gender with brainstem and thalamus volumes
      were analyzed from magnetic resonance brain images of 122 healthy children and
      adolescents (62 males, 60 females; ages 4 to 17). Results showed that age is a
      significant predictor of brainstem and thalamus volumes. The volume of the
      brainstem increases with age, while thalamus volume declines with age. The volume
      of the right thalamus is significantly larger than that of the left in both
      genders, with greater rightward asymmetry and greater thalamus to grey matter
      ratio in females. Males have larger brainstems, but these differences are not
      significant when covarying for cerebral volume. Larger thalami were associated
      with higher Verbal IQ. These normative pediatric data are of value to researchers
      who study these regions in neurodevelopmental disorders.

PMID- 21954434
TI  - Constitutive aberrant endogenous interleukin-1 facilitates inflammation and
      growth in human melanoma.
AB  - Interleukin (IL)-1-mediated inflammation is proposed to contribute to the
      development and progression of some cancers. IL-1 family member proteins are
      known to be expressed constitutively in many melanoma tumor cells, and we
      hypothesize that these support molecular pathways of inflammation and facilitate
      tumor growth. To investigate the expression of IL-1alpha and IL-1beta in melanoma
      patients, and their association with disease progression, immunohistochemical
      staining was carried out on tissues from 170 patients including benign nevi,
      primary melanomas, and metastatic melanomas. IL-1beta levels were low (or zero)
      in benign nevi and higher in primary and metastatic melanomas (P < 0.0001). IL
      1alpha was expressed in about 73% of nevi and 55% of metastatic melanomas, with
      levels significantly higher in primary tumors (P < 0.0001); most (98%) primary
      melanoma samples were positive for IL-1alpha. In vitro studies with seven human
      melanoma cell lines showed that five cell lines expressed IL-1alpha and IL-1beta
      proteins and mRNA. We identified for the first time several important downstream
      signaling pathways affected by endogenous IL-1, including reactive oxygen and
      nitrogen species, COX-2, and phosphorylated NF-kappaB inhibitor (IkappaB) and
      stress-activated protein kinase/c-jun-NH(2)-kinase; all of which were decreased
      by siRNA to IL-1s. Downregulation of IL-1alpha, IL-1beta, or MyD88 substantially
      increased p21 and p53 levels. Treatment with IL-1 receptor type I neutralizing
      antibody or IL-1 pathway-specific siRNAs led to growth arrest in IL-1-positive
      melanoma cells. Furthermore, blocking the IL-1 pathway increased autophagy in IL
      1-positive melanoma cells. These results indicate that the endogenous IL-1 system
      is functional in most human melanoma and interrupting its signaling inhibits the
      growth of IL-1-positive melanoma cells.

PMID- 21954435
TI  - Cancer cell dependence on unsaturated fatty acids implicates stearoyl-CoA
      desaturase as a target for cancer therapy.
AB  - Emerging literature suggests that metabolic pathways play an important role in
      the maintenance and progression of human cancers. In particular, recent studies
      have implicated lipid biosynthesis and desaturation as a requirement for tumor
      cell survival. In the studies reported here, we aimed to understand whether tumor
      cells require the activity of either human isoform of stearoyl-CoA-desaturase
      (SCD1 or SCD5) for survival. Inhibition of SCD1 by siRNA or a small molecule
      antagonist results in strong induction of apoptosis and growth inhibition, when
      tumor cells are cultured in reduced (2%) serum conditions, but has little impact
      on cells cultured in 10% serum. Depletion of SCD5 had minimal effects on cell
      growth or apoptosis. Consistent with the observed dependence on SCD1, but not
      SCD5, levels of SCD1 protein increased in response to decreasing serum levels.
      Both induction of SCD1 protein and sensitivity to growth inhibition by SCD1
      inhibition could be reversed by supplementing growth media with unsaturated fatty
      acids, the product of the enzymatic reaction catalyzed by SCD1. Transcription
      profiling of cells treated with an SCD inhibitor revealed strong induction of
      markers of endoplasmic reticulum stress. Underscoring its importance in cancer,
      SCD1 protein was found to be highly expressed in a large percentage of human
      cancer specimens. SCD inhibition resulted in tumor growth delay in a human
      gastric cancer xenograft model. Altogether, these results suggest that
      desaturated fatty acids are required for tumor cell survival and that SCD may
      represent a viable target for the development of novel agents for cancer therapy.

PMID- 21954436
TI  - Differential expression of uridine phosphorylase in tumors contributes to an
      improved fluoropyrimidine therapeutic activity.
AB  - Abrogation of uridine phosphorylase (UPase) leads to abnormalities in pyrimidine
      metabolism and host protection against 5-fluorouracil (5-FU) toxicity. We
      elucidated the effects on the metabolism and antitumor efficacy of 5-FU and
      capecitabine (N(4)-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine) in our UPase
      knockout (UPase(-/-)) model. Treatment with 5-FU (85 mg/kg) or capecitabine
      (1,000 mg/kg) five days a week for four weeks caused severe toxicity and
      structural damage to the intestines of wild-type (WT) mice, but not in UPase(-/-)
      animals. Capecitabine treatment resulted in a 70% decrease in blood cell counts
      of WT animals, with only a marginal effect in UPase(-/-) mice. UPase expressing
      colon 38 tumors implanted in UPase(-/-) mice revealed an improved therapeutic
      efficacy when treated with 5-FU and capecitabine because of the higher maximum
      tolerated dose for fluoropyrimidines achievable in UPase(-/-) mice. (19)F-MRS
      evaluation of capecitabine metabolism in tumors revealed similar activation of
      the prodrug in UPase(-/-) mice compared with WT. In WT mice, approximately 60% of
      capecitabine was transformed over three hours into its active metabolites,
      whereas 80% was transformed in tumors implanted in UPase(-/-) mice. In UPase(-/-)
      mice, prolonged retention of 5'dFUR allowed a proportional increase in tumor
      tissue. The similar presence of fluorinated catabolic species confirms that
      dihydropyrimidine dehydrogenase activity was not altered in UPase(-/-) mice.
      Overall, these results indicate the importance of UPase in the activation of
      fluoropyrimidines, the effect of uridine in protecting normal tissues, and the
      role for tumor-specific modulation of the phosphorolytic activity in 5-FU or
      capecitabine-based chemotherapy.

PMID- 21954438
TI  - Sequence-structure relationships in yeast mRNAs.
AB  - It is generally accepted that functionally important RNA structure is more
      conserved than sequence due to compensatory mutations that may alter the sequence
      without disrupting the structure. For small RNA molecules sequence-structure
      relationships are relatively well understood. However, structural bioinformatics
      of mRNAs is still in its infancy due to a virtual absence of experimental data.
      This report presents the first quantitative assessment of sequence-structure
      divergence in the coding regions of mRNA molecules based on recently published
      transcriptome-wide experimental determination of their base paring patterns.
      Structural resemblance in paralogous mRNA pairs quickly drops as sequence
      identity decreases from 100% to 85-90%. Structures of mRNAs sharing sequence
      identity below roughly 85% are essentially uncorrelated. This outcome is in
      dramatic contrast to small functional non-coding RNAs where sequence and
      structure divergence are correlated at very low levels of sequence similarity.
      The fact that very similar mRNA sequences can have vastly different secondary
      structures may imply that the particular global shape of base paired elements in
      coding regions does not play a major role in modulating gene expression and
      translation efficiency. Apparently, the need to maintain stable three-dimensional
      structures of encoded proteins places a much higher evolutionary pressure on mRNA
      sequences than on their RNA structures.

PMID- 21954437
TI  - A dual role of BRCA1 in two distinct homologous recombination mediated repair in
      response to replication arrest.
AB  - Homologous recombination (HR) is a major mechanism utilized to repair blockage of
      DNA replication forks. Here, we report that a sister chromatid exchange (SCE)
      generated by crossover-associated HR efficiently occurs in response to
      replication fork stalling before any measurable DNA double-strand breaks (DSBs).
      Interestingly, SCE produced by replication fork collapse following DNA DSBs
      creation is specifically suppressed by ATR, a central regulator of the
      replication checkpoint. BRCA1 depletion leads to decreased RPA2 phosphorylation
      (RPA2-P) following replication fork stalling but has no obvious effect on RPA2-P
      following replication fork collapse. Importantly, we found that BRCA1 promotes
      RAD51 recruitment and SCE induced by replication fork stalling independent of
      ATR. In contrast, BRCA1 depletion leads to a more profound defect in RAD51
      recruitment and SCE induced by replication fork collapse when ATR is depleted. We
      concluded that BRCA1 plays a dual role in two distinct HR-mediated repair upon
      replication fork stalling and collapse. Our data established a molecular basis
      for the observation that defective BRCA1 leads to a high sensitivity to agents
      that cause replication blocks without being associated with DSBs, and also
      implicate a novel mechanism by which loss of cell cycle checkpoints promotes
      BRCA1-associated tumorigenesis via enhancing HR defect resulting from BRCA1
      deficiency.

PMID- 21954439
TI  - Untwisting of the DNA helix stimulates the endonuclease activity of Bacillus
      subtilis Nth at AP sites.
AB  - Bacterial nucleoid associated proteins play a variety of roles in genome
      maintenance and dynamics. Their involvement in genome packaging, DNA replication
      and transcription are well documented but it is still unclear whether they play
      any specific roles in genome repair. We discovered that untwisting of the DNA
      double helix by bacterial non-specific DNA binding proteins stimulates the
      activity of a repair endonuclease of the Nth/MutY family involved in abasic site
      removal during base excision repair. The essential Bacillus subtilis primosomal
      gene dnaD, coding for a protein with DNA-untwisting activity, is in the same
      operon with nth and the promoter activity of this operon is transiently
      stimulated by H(2)O(2). Consequently, dnaD mRNA levels persist high upon
      treatment with H(2)O(2) compared to the reduced mRNA levels of the other
      essential primosomal genes dnaB and dnaI, suggesting that DnaD may play an
      important role in DNA repair in addition to its essential role in replication
      initiation. Homologous Nth repair endonucleases are found in nearly all
      organisms, including humans. Our data have wider implications for DNA repair as
      they suggest that genome associated proteins that alter the superhelicity of the
      DNA indirectly facilitate base excision repair mediated by repair endonucleases
      of the Nth/MutY family.

PMID- 21954440
TI  - Recognition of prokaryotic promoters based on a novel variable-window Z-curve
      method.
AB  - Transcription is the first step in gene expression, and it is the step at which
      most of the regulation of expression occurs. Although sequenced prokaryotic
      genomes provide a wealth of information, transcriptional regulatory networks are
      still poorly understood using the available genomic information, largely because
      accurate prediction of promoters is difficult. To improve promoter recognition
      performance, a novel variable-window Z-curve method is developed to extract
      general features of prokaryotic promoters. The features are used for further
      classification by the partial least squares technique. To verify the prediction
      performance, the proposed method is applied to predict promoter fragments of two
      representative prokaryotic model organisms (Escherichia coli and Bacillus
      subtilis). Depending on the feature extraction and selection power of the
      proposed method, the promoter prediction accuracies are improved markedly over
      most existing approaches: for E. coli, the accuracies are 96.05% (sigma(70)
      promoters, coding negative samples), 90.44% (sigma(70) promoters, non-coding
      negative samples), 92.13% (known sigma-factor promoters, coding negative
      samples), 92.50% (known sigma-factor promoters, non-coding negative samples),
      respectively; for B. subtilis, the accuracies are 95.83% (known sigma-factor
      promoters, coding negative samples) and 99.09% (known sigma-factor promoters, non
      coding negative samples). Additionally, being a linear technique, the
      computational simplicity of the proposed method makes it easy to run in a matter
      of minutes on ordinary personal computers or even laptops. More importantly,
      there is no need to optimize parameters, so it is very practical for predicting
      other species promoters without any prior knowledge or prior information of the
      statistical properties of the samples.

PMID- 21954441
TI  - Hydride abstraction in positive-ion electrospray interface: oxidation of 1,4
      dihydropyridines in electrospray ionization mass spectrometry.
AB  - During the positive-ion mode electrospray ionization mass spectrometry analysis
      of 1,4-diphenyl-3-benzoyl-1,4-dihydropyridines with methanol as the solvent, the
      major ion generated is one mass unit lower than the analyte, which can be
      rationalized as the oxidative aromatization of 1,4-dihydropyridines to pyridine
      cations.

PMID- 21954442
TI  - Phase I trial of sorafenib in patients with recurrent or progressive malignant
      glioma.
AB  - Sorafenib is an inhibitor of multiple kinases that has demonstrated
      antiproliferative and antiangiogenic activity in a number of in vitro and in vivo
      model systems. A phase I study was conducted to determine the maximum tolerated
      dose (MTD) of sorafenib in patients with recurrent malignant glioma. Sorafenib
      was given orally, twice a day (BID), continuously in 28-day cycles. The dose was
      escalated in 2 groups of patients stratified by use of enzyme-inducing
      antiseizure drugs (+/- EIASDs). Dose-limiting toxicity (DLT) was defined as any
      grades 3-4 nonhematological toxicity, grade 4 hematological toxicity, and febrile
      neutropenia. The number of evaluable patients enrolled in the +EIASD and -EIASD
      arms were 23 and 24, respectively. DLTs were predominantly dermatological and
      gastrointestinal effects, as observed in previous clinical trials of sorafenib.
      The MTD was 600 mg BID for patients receiving EIASDs and 800 mg BID for those who
      were not. The plasma pharmacokinetics of sorafenib were not significantly
      affected by the concurrent administration of EIASDs. The MTD of sorafenib given
      orally BID on a continuous basis was established as 600 mg BID in patients with
      malignant glioma who were concurrently receiving EIASDs and 800 mg BID in those
      who were not. Further evaluation is warranted of sorafenib at the recommended MTD
      against recurrent or progressive malignant glioma in combination with other
      molecularly targeted drugs or in the newly diagnosed setting concurrent with
      chemoradiation.

PMID- 21954443
TI  - Investigation of intravenous delivery of nanoliposomal topotecan for activity
      against orthotopic glioblastoma xenografts.
AB  - Achieving effective treatment outcomes for patients with glioblastoma (GBM) has
      been impeded by many obstacles, including the pharmacokinetic limitations of
      antitumor agents, such as topotecan (TPT). Here, we demonstrate that intravenous
      administration of a novel nanoliposomal formulation of TPT (nLS-TPT) extends the
      survival of mice with intracranial GBM xenografts, relative to administration of
      free TPT, because of improved biodistribution and pharmacokinetics of the
      liposome-formulated drug. In 3 distinct orthotopic GBM models, 3 weeks of
      biweekly intravenous therapy with nLS-TPT was sufficient to delay tumor growth
      and significantly extend animal survival, compared with treatment with free TPT
      (P <= .03 for each tumor tested). Analysis of intracranial tumors showed
      increased activation of cleaved caspase-3 and increased DNA fragmentation, both
      indicators of apoptotic response to treatment with nLS-TPT. These results
      demonstrate that intravenous delivery of nLS-TPT is a promising strategy in the
      treatment of GBM and support clinical investigation of this therapeutic approach.

PMID- 21954444
TI  - HRE-type genes are regulated by growth-related changes in internal oxygen
      concentrations during the normal development of potato (Solanum tuberosum)
      tubers.
AB  - The occurrence of hypoxic conditions in plants not only represents a stress
      condition but is also associated with the normal development and growth of many
      organs, leading to adaptive changes in metabolism and growth to prevent internal
      anoxia. Internal oxygen concentrations decrease inside growing potato tubers, due
      to their active metabolism and increased resistance to gas diffusion as tubers
      grow. In the present work, we identified three hypoxia-responsive ERF (StHRE)
      genes whose expression is regulated by the gradual decrease in oxygen tensions
      that occur when potato tubers grow larger. Increasing the external oxygen
      concentration counteracted the modification of StHRE expression during tuber
      growth, supporting the idea that the actual oxygen levels inside the organs,
      rather than development itself, are responsible for the regulation of StHRE
      genes. We identified several sugar metabolism-related genes co-regulated with
      StHRE genes during tuber development and possibly involved in starch
      accumulation. All together, our data suggest a possible role for low oxygen in
      the regulation of sugar metabolism in the potato tuber, similar to what happens
      in storage tissues during seed development.

PMID- 21954446
TI  - Treatment of IgA nephropathy: an update.
AB  - OBJECTIVE: To review current literature regarding treatment options for
      immunoglobulin A nephropathy (IgAN). DATA SOURCES: A MEDLINE search was performed
      using the terms IgA nephropathy, Berger's disease, immunoglobulin A nephropathy,
      angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, fish
      oil, omega-3 fatty acids, statins, hydroxymethylglutaryl-CoA reductase
      inhibitors, immunosuppressive therapy, corticosteroids, mycophenolate mofetil,
      cyclophosphamide, cyclosporine, azathioprine, leflunomide, antiplatelets,
      anticoagulants, vitamin E, infliximab, calcitriol, and intravenous
      immunoglobulins. A date limit was not set; however, focus was on publications
      from 1999 to June 2011 to review recent literature and therapeutic
      recommendations. STUDY SELECTION AND DATA EXTRACTION: All articles in English,
      including studies conducted in humans, meta-analyses, review articles,
      guidelines, statements, and reference citations, were identified and evaluated.
      DATA SYNTHESIS: IgAN is the most common primary glomerulonephritis worldwide,
      leading to end-stage renal disease in 20-30% of patients. Evidence guiding
      management of IgAN has been sparse and clinical trials have not conclusively
      demonstrated effective treatments, largely due to suboptimal methodologies.
      Treatment strategies have included management of blood pressure and lipids,
      improvement or stabilization of kidney function, and reduction of proteinuria.
      This review of IgAN provides an update regarding standard and nonconventional
      treatment options based on recently published literature. CONCLUSIONS: Supportive
      therapies, including angiotensin blockade, should be considered as first-line
      therapy for patients with urine protein >0.5 g/day and/or blood pressure >140/90
      mm Hg. Corticosteroids could be considered as add-on or monotherapy for patients
      with urine protein >1 g/day with preserved renal function. Conclusive data are
      lacking for general treatment recommendations for the use of other therapies for
      IgAN.

PMID- 21954447
TI  - Probiotics for disease prevention: a focus on ventilator-associated pneumonia.
AB  - OBJECTIVE: To summarize published data regarding the safety and efficacy of
      probiotics in the prevention of ventilator-associated pneumonia (VAP). DATA
      SOURCES: PubMed databases (January 2000-August 2011) were searched and a
      bibliographic review of published articles was performed to identify original
      reports of probiotic administration for the prevention of VAP using the search
      terms probiotics, synbiotics, and ventilator-associated pneumonia. STUDY
      SELECTION AND DATA EXTRACTION: Two pilot studies, 2 randomized controlled trials
      (RCTs), and 1 meta-analysis have addressed probiotic use for VAP prevention and
      were included in the review. DATA SYNTHESIS: VAP frequently occurs in
      mechanically ventilated patients. Given the lack of new antimicrobial agents,
      probiotics have been studied for their ability to modify human microflora
      colonization. Two studies examining pathogen colonization rates favored
      probiotics, with reduced incidence and increased duration until the emergence of
      new species. One prospective RCT found significant reduction in the incidence of
      VAP and colonization rates, but no significant difference in patient disposition
      outcomes. Another RCT examining 28-day mortality found no overall benefit with
      probiotic use and no reduction in colonization rates. CONCLUSIONS: Clinical
      trials have failed to demonstrate a consistent beneficial effect of probiotics in
      mechanically ventilated patients; thus, they are not recommended for routine
      clinical use. However, heterogeneity among study designs may hinder this
      assessment and the designs should be unified in future research.

PMID- 21954448
TI  - Osteonecrosis of the jaw in older osteoporosis patients treated with intravenous
      bisphosphonates.
AB  - BACKGROUND: Intravenous bisphosphonate therapy has been linked to osteo-necrosis
      of the jaw among patients with cancer. Some patients with osteoporosis also
      receive intravenous bisphosphonates, although at lower total doses than those
      with cancer. OBJECTIVE: To examine the risk for jaw osteonecrosis among a
      population-based cohort of older adults receiving intravenous bisphosphonates for
      the treatment of osteoporosis. METHODS: Using a 5% national sample of Medicare
      beneficiaries, we identified 2296 patients treated with intravenous infusions of
      bisphosphonates for osteoporosis and other metabolic bone diseases between
      January 1, 2000, and December 31, 2007. We matched this cohort to 6865
      bisphosphonate nonusers, at a 1:3 ratio, on age, race, sex, type of bone disease,
      and risk factors for osteonecrosis of the jaw. Patients were followed until
      December 31, 2007. The jaw toxicity outcomes included operations on the facial
      bones or jaw and diagnosis of inflammatory conditions of the jaw. RESULTS: The
      absolute risk at 3 years for any jaw toxicity was 0.70 events per 100 patients
      using bisphosphonates and 0.30 events per 100 patients not using such drugs (2
      sided log rank test, p = 0.08). In multivariable survival analyses (Cox
      proportional hazards regression) adjusting for potential confounders, intravenous
      bisphosphonate use was not significantly associated with diagnoses or procedures
      suggestive of osteonecrosis of the jaw (p = 0.24). CONCLUSIONS: Patients with
      osteoporosis who are treated with intravenous bisphosphonates do not appear to
      have a statistically significant increase in the incidence of osteonecrosis of
      the jaw over 3 years compared with those who do not receive such treatment.
      Future studies will further contribute to our understanding of the bisphosphonate
      risk profile, thereby allowing patients and physicians to more rigorously assess
      the risk-benefit ratio of this treatment across different clinical scenarios.

PMID- 21954449
TI  - Sunitinib-induced hyperammonemic encephalopathy in gastrointestinal stromal
      tumors.
AB  - OBJECTIVE: To report 2 cases of hyperammonemic encephalopathy induced by
      sunitinib in patients with metastatic gastrointestinal stromal tumor (GIST). CASE
      SUMMARY: A 58-year-old man with imatinib-resistant metastatic GIST presented to
      the emergency department with confusion that developed 17 days after the
      initiation of sunitinib 50 mg/day. His serum ammonia level was markedly elevated
      (210 MUg/dL). Sunitinib was discontinued, and an enema with lactulose was
      administered every hour. His neurologic status normalized within 24 hours and his
      serum ammonia level decreased to 64 MUg/dL. A 68-year-old woman with imatinib
      resistant metastatic GIST was admitted into the emergency department with
      confusion and irritability that developed 10 days after the start of sunitinib
      therapy. Her serum ammonia level was markedly elevated (389 MUg/dL). Sunitinib
      was discontinued, and an enema with lactulose was administered every hour. Within
      24 hours, her mental status was improved and her serum ammonia level was
      decreased to 116 MUg/dL. Sunitinib was reintroduced, and the same symptoms
      occurred after day 7 of administration. Sunitinib was not prescribed afterward
      and the woman did not experience any further encephalopathic symptoms.
      DISCUSSION: Sunitinib is a small molecule that inhibits multiple receptor
      tyrosine kinases such as stem cell factor receptor, vascular endothelial growth
      factor, and platelet-derived growth factor. It is used as second-line therapy for
      patients with imatinib-resistant GIST. Hyperammonemic encephalopathy is an
      uncommon fatal complication of chemotherapy. According to the Naranjo probability
      scale, sunitinib was a probable cause of hyperammonemic encephalopathy in the
      patients described here. Although the mechanism of hyperammonemia is unclear,
      hyperammonemic encephalopathy might be caused by a vascular disorder related to
      the antiangiogenic properties of sunitinib, and it has ethnic differences
      associated with genetic polymorphisms. CONCLUSIONS: Sunitinib may induce
      hyperammonemic encephalopathy in some patients. Although further studies are
      warranted, clinicians should be aware of this severe adverse event when using
      sunitinib for treatment of GIST.

PMID- 21954450
TI  - The role of apixaban for venous and arterial thromboembolic disease.
AB  - OBJECTIVE: To provide a comprehensive review of the pharmacology,
      pharmacokinetics, pharmacodynamics, clinical trial data, adverse effects, and
      drug interactions of apixaban. DATA SOURCES: An English-language literature
      search was performed with MEDLINE/PubMed from January 2007 to August 2011 using
      the search terms apixaban, factor Xa inhibitors, FXa inhibitors, BMS-562247-01,
      venous thromboembolism, deep vein thrombosis, pulmonary embolism, myocardial
      infarction, acute coronary syndrome, ACS, atrial fibrillation, atrial
      arrhythmias, total hip replacement or arthroplasty, total knee replacement or
      arthroplasty, and orthopedic surgery to identify relevant articles. The
      references of the retrieved articles, professional society meeting abstracts, and
      the Web site www.clinicaltrials.gov were reviewed to identify other pertinent
      articles. STUDY SELECTION AND DATA ABSTRACTION: Pertinent original studies
      involving apixaban's pharmacology, pharmacokinetics, drug interactions, and
      clinical efficacy and safety data were included. DATA SYNTHESIS: Results of 2
      large Phase 3 trials suggest that apixaban is superior for stroke and systemic
      embolism prevention compared to both aspirin and warfarin in patients with atrial
      fibrillation (AF); rates of major bleeding and intracranial hemorrhage were
      similar to those of aspirin but significantly reduced compared to warfarin.
      Completed trials in orthopedic surgery found apixaban to be superior to
      enoxaparin in total hip replacement (THR) surgery but inferior in total knee
      replacement (TKR) surgery, with similar rates of major bleeding. A Phase 3 trial
      of apixaban in acute coronary syndrome was stopped early because of excess
      bleeding. Future Phase 3 trials will help to determine apixaban's role for
      treatment of deep vein thrombosis and pulmonary embolism. Currently, apixaban is
      approved only in Europe for prophylaxis of venous thromboembolism in adults who
      have undergone elective THR or TKR. CONCLUSIONS: A Phase 3 trial in patients with
      AF revealed apixaban to be superior to warfarin for stroke and systemic embolism
      prophylaxis, with lower rates of major bleeding. Further studies will help to
      confirm the role of apixaban for other indications.

PMID- 21954452
TI  - Fetal HDL/apoE: a novel regulator of gene expression in human placental
      endothelial cells.
AB  - Maternal lipoproteins have been studied extensively in human pregnancies, but
      little is known about the role of fetal lipoproteins. The vascularized human
      placenta interfaces between the mother and fetus to transfer nutrients for
      sustaining pregnancy. Unlike that of adults, fetal high-density lipoprotein
      (HDL), which is in contact with placental vessels, is characterized by a high
      proportion of apolipoprotein E (apoE). We hypothesize this unique composition of
      fetal HDL affects key functions of the growing fetal tissues. The aim was to
      identify genes regulated by apoE-HDL by incubating human placental endothelial
      cells (HPEC) with either fetal HDL or apoE-rich reconstituted HDL particles (apoE
      rHDL). HPEC were exposed to 15 MUg/ml fetal HDL, 15 MUg/ml apoE-rHDL, or medium
      for 16 h, respectively. Microarray analysis determined genes regulated by fetal
      HDL and apoE. Characterization of HDL particles revealed a different hydrodynamic
      radius for apoE-rHDL (13.70 nm) compared with fetal HDL (18.11 nm). Stepwise gene
      clustering after microarray experiments identified 79 differentially expressed
      genes (P < 0.05) when cells were exposed to HDL compared with controls. Among
      them 16 genes were downregulated, whereas five genes were upregulated by twofold,
      respectively. When HPEC were incubated with apoE-rHDL 18-fold more genes (1,417,
      12% of transcripts) were regulated (P < 0.05) in contrast to HDL. Thereof, 172
      genes were downregulated and 376 genes upregulated (twofold). In the common
      subset of 38 genes regulated by both HDL particles, genes involved in cholesterol
      biosynthesis and cell protection prevailed. Strikingly, results suggest that HDL
      has the capability of regulating metallothioneins, which may have an effect on
      oxidative stress in HPEC.

PMID- 21954451
TI  - Panhistone deacetylase inhibitors inhibit proinflammatory signaling pathways to
      ameliorate interleukin-18-induced cardiac hypertrophy.
AB  - We investigated the genome-wide consequences of pan-histone deacetylase
      inhibitors (HDACIs) trichostatin A (TSA) and m-carboxycinnamic acid bis
      hydroxamide (CBHA) in the hearts of BALB/c mice eliciting hypertrophy in response
      to interleukin-18 (IL-18). Both TSA and CBHA profoundly altered cardiac chromatin
      structure that occurred concomitantly with normalization of IL-18-induced gene
      expression and amelioration of cardiac hypertrophy. The hearts of mice exposed to
      IL-18+/-TSA or CBHA elicited distinct gene expression profiles. Of 184 genes that
      were differentially regulated by IL-18 and TSA, 33 were regulated in an opposite
      manner. The hearts of mice treated with IL-18 and/or CBHA elicited 147
      differentially expressed genes (DEGs), a third of which were oppositely regulated
      by IL-18 and CBHA. Ingenuity Pathways and Kyoto Encyclopedia of Genes and Genomes
      analyses of DEGs showed that IL-18 impinged on TNF-alpha- and IFNgamma-specific
      gene networks relegated to controlling immunity and inflammation, cardiac
      metabolism and energetics, and cell proliferation and apoptosis. These TNF-alpha-
      and IFNgamma-specific gene networks, extensively connected with PI3K, MAPK, and
      NF-kappaB signaling pathways, were oppositely regulated by IL-18 and pan-HDACIs.
      Evidently, both TSA and CBHA caused a two- to fourfold induction of phosphatase
      and tensin homolog expression to counteract IL-18-induced proinflammatory
      signaling and cardiac hypertrophy.

PMID- 21954453
TI  - Formula feeding alters hepatic gene expression signature, iron and cholesterol
      homeostasis in the neonatal pig.
AB  - In the U.S. formula feeding remains more popular than breast-feeding. In the
      current study, neonatal piglets were breast fed and compared with those fed
      commercially available milk-based formula (milk) or soy-based formula (soy) from
      postnatal day 2 (PND2) until death at PND21 (the usual age of weaning). Liver
      weights were greater in formula-fed piglets (P<0.05) than in breast-fed piglets
      (P<0.05). Affymetrix array analysis revealed significant differences in hepatic
      gene expression signatures between piglets fed breast milk or formula, as well as
      between piglets fed milk or soy. In males, expression of 346 hepatic genes
      differed between formula-fed and breast-fed piglets, and soy-fed differed from
      milk-fed piglets in 277 genes. Furthermore, gene expression profiles of males
      differed from females, even when the same diet was consumed. Serum cholesterol
      was lower in piglets fed formula relative to breast-fed piglets (P<0.05), and
      this was associated with elevations in mRNA encoding cholesterol 7alpha
      hydroxylase (CYP7A1). Consistent with the human literature, breast-fed piglets
      had lower hepatic iron accumulation than formula-fed piglets. Hepcidin, a major
      regulator of hepatic iron trafficking, was elevated in piglets fed formula
      relative to breast-fed piglets (P<0.05). Female piglets fed soy formula had
      increased expression of CYP3A enzymes (P<0.05), and soy formula feeding decreased
      expression of several hepatic genes considered estrogen inducible. These data
      suggest that: 1) gene expression profiles in neonates differ significantly
      depending on the diet consumed, 2) hepatic iron storage and cholesterol
      metabolism clearly differ between breast and formula feeding in piglets, 3) there
      is no evidence that soy is estrogenic in neonatal pig liver.

PMID- 21954454
TI  - Comparative transcriptomic and metabolomic analysis of fenofibrate and fish oil
      treatments in mice.
AB  - Elevated circulating triglycerides, which are considered a risk factor for
      cardiovascular disease, can be targeted by treatment with fenofibrate or fish
      oil. To gain insight into underlying mechanisms, we carried out a comparative
      transcriptomics and metabolomics analysis of the effect of 2 wk treatment with
      fenofibrate and fish oil in mice. Plasma triglycerides were significantly
      decreased by fenofibrate (-49.1%) and fish oil (-21.8%), whereas plasma
      cholesterol was increased by fenofibrate (+29.9%) and decreased by fish oil (
      32.8%). Levels of various phospholipid species were specifically decreased by
      fish oil, while levels of Krebs cycle intermediates were increased specifically
      by fenofibrate. Plasma levels of many amino acids were altered by fenofibrate and
      to a lesser extent by fish oil. Both fenofibrate and fish oil upregulated genes
      involved in fatty acid metabolism and downregulated genes involved in blood
      coagulation and fibrinolysis. Significant overlap in gene regulation by
      fenofibrate and fish oil was observed, reflecting their property as high or low
      affinity agonist for peroxisome proliferator-activated receptor-alpha,
      respectively. Fenofibrate specifically downregulated genes involved in complement
      cascade and inflammatory response. Fish oil specifically downregulated genes
      involved in cholesterol and fatty acid biosynthesis and upregulated genes
      involved in amino acid and arachidonic acid metabolism. Taken together, the data
      indicate that despite being similarly potent toward modulating plasma free fatty
      acids, cholesterol, and triglyceride levels, fish oil causes modest changes in
      gene expression likely via activation of multiple mechanistic pathways, whereas
      fenofibrate causes pronounced gene expression changes via a single pathway,
      reflecting the key difference between nutritional and pharmacological
      intervention.

PMID- 21954455
TI  - Temporal analysis of mRNA and miRNA expression in transgenic mice overexpressing
      Arg- and Gly389 polymorphic variants of the beta1-adrenergic receptor.
AB  - Several studies in humans or transgenic animals have reported that the 389 Arg or
      Gly polymorphic variation of the beta1-adrenergic receptor (AR) is associated
      with differential responses to beta-blocker therapy and/or myocardial disease
      progression. Analysis of changes in gene expression is an important means of
      defining molecular differences associated with structural or functional
      phenotypic variations. To determine if structural and functional myocardial
      phenotypic differences between beta1389 Arg vs. Gly transgenic overexpressors are
      associated with qualitative and/or quantitative differences in gene expression, a
      comprehensive analysis of mRNAs and miRNAs expressed in the hearts of 3 and 6-8
      mo old beta1-Arg389 and beta1-Gly389 overexpressor transgenic mice was performed.
      Changes in mRNA and miRNA expression were analyzed by arrays and partially
      confirmed by RT-qPCR. Bioinformatic analysis demonstrated that several genes,
      including those involved in PKA and CaMK signaling pathways, are regulated in a
      temporal- or phenotype-specific manner. Furthermore, expression signature
      analyses indicated that miRNAs have the potential to target expression of a
      number of genes involved in multiple cardiomyopathy-related pathways, and changes
      in miRNA expression can precede the onset of disease. Differences in gene
      expression between beta1-Arg389 and beta1-Gly389 transgenic mice are largely
      quantitative rather than qualitative and are associated with the development of
      cardiomyopathy in a time-dependent manner. Chronic beta1-AR overdrive results in
      increased expression of components of the CaMK pathway, with correspondingly
      decreased levels of components of the PKA pathway. Based on the temporal and
      genotype-specific pattern of miRNA expression, miRNAs are likely to be important
      predictors of disease states, especially when miRNA expression is paired with
      mRNA expression, and that miRNA/mRNA expression signatures have the potential to
      be useful in determining the underlying risk associated with cardiac disease
      progression.

PMID- 21954456
TI  - Antibiotic use in long-term care facilities.
AB  - OBJECTIVES: Evaluation and optimization of antibiotic use (antibiotic
      stewardship) is being increasingly promoted as a means to reduce antibiotic
      resistance, adverse events, treatment complications and costs within
      institutions. Our goal was to examine the prevalence of antibiotic use among long
      term care facility residents and the extent of variability across these
      institutions. METHODS: We conducted a population-based, point-prevalence study of
      antibiotic use among elderly individuals (n = 37,371) residing in long-term care
      facilities (n = 363 institutions) in Ontario between April and June 2009, using
      linked healthcare databases from Canada's largest province. Facilities were
      grouped into quintiles according to their mean antibiotic dispensing rates and
      variation was compared across quintiles. RESULTS: There were 2190 (5.9%) long
      term care residents receiving antibiotic prescriptions on the study date. The
      three most prevalent antibiotics were agents most commonly used for the treatment
      of urinary tract infections, including nitrofurantoin (365, 15.4%),
      trimethoprim/sulfamethoxazole (338, 14.3%) and ciprofloxacin (304, 12.8%). The
      majority of treatment courses were at least 10 days in duration (1482, 62.6%),
      and many exceeded 90 days (495, 20.9%), suggesting chronic prophylaxis. There was
      substantial variability in antibiotic use across facilities, with a 5-fold
      variation from the highest-use quintile (10.8%) to the lowest-use quintile
      (2.2%). This variation persisted after adjustment for multiple facility-level and
      resident-level factors, including demographic characteristics, healthcare
      utilization statistics, co-morbidity prevalence, functional status and device
      dependence. CONCLUSIONS: Antibiotic use is common among long-term care residents,
      variable across institutions, and may benefit from focused antimicrobial
      stewardship interventions to standardize treatment indications and duration.

PMID- 21954457
TI  - CTX-M-15-producing Escherichia coli clone B2-O25b-ST131 and Klebsiella spp.
      isolates in municipal wastewater treatment plant effluents.
AB  - OBJECTIVES: The global occurrence of antibiotic resistance genes in bacteria in
      water environments is an increasing concern. Treated wastewater was sampled daily
      over a 45 day period from the outflow of a municipal wastewater treatment plant
      in Brno, Czech Republic, and examined for extended-spectrum beta-lactamase (ESBL)
      producing bacteria. METHODS: Water samples were cultivated on MacConkey agar with
      cefotaxime (2 mg/L) and individual colonies were examined for ESBL production.
      Phenotypic ESBL-positive bacteria identified as Escherichia coli or Klebsiella
      spp. were tested for the presence of antibiotic resistance genes, the virulence
      gene afa/dra and the bla(CTX-M) upstream region. Genetic relatedness was analysed
      by PFGE, multilocus sequence typing and plasmid analysis. RESULTS: A total of 68
      ESBL-producing Enterobacteriaceae isolates were detected in 34 out of 45
      wastewater samples. ESBL-producing isolates included 26 E. coli isolates, 4
      Klebsiella pneumoniae isolates and 1 Klebsiella oxytoca isolate. The pandemic and
      multiresistant B2-O25b-ST131 clone was predominant, being detected among 19 E.
      coli isolates, and 17 of the B2-O25b-ST131 isolates were positive for the FIA
      replicon and the afa/dra operon and had an IS26 element flanking bla(CTX-M-15).
      Seventeen of the B2-O25b-ST131 isolates showed closely related PFGE profiles
      (defined by 84% band similarity) and belonged to identical clonal groups.
      CONCLUSIONS: The results highlight the inadequacy of the treatment process in
      removing multiresistant bacteria from municipal wastewater and point to a risk of
      transmission of clinically important multiresistant strains, such as the pandemic
      ST131 clone, to the environment. This is the first study demonstrating the
      pandemic ST131 clone in wastewater.

PMID- 21954458
TI  - In vitro activity of tedizolid (TR-700) against linezolid-resistant
      staphylococci.
AB  - OBJECTIVES: To compare the activity of tedizolid (formally known as torezolid and
      TR-700) with that of 15 agents against a collection of linezolid-resistant
      staphylococci (164 coagulase-negative staphylococci and 5 Staphylococcus aureus).
      METHODS: Antimicrobial susceptibility tests were performed using the broth
      microdilution method following the recommendations of the CLSI. RESULTS: All
      isolates were susceptible to vancomycin and tigecycline. Based on the MIC(90)
      values, the potency of tedizolid against coagulase-negative staphylococci was >16
      fold greater than that of linezolid. Tedizolid retained activity against most of
      the linezolid-resistant staphylococci tested, including multidrug-resistant
      isolates with elevated linezolid MICs (32 to >128 mg/L). Of the isolates, 79.2%
      and 31.4% were inhibited by tedizolid at <= 4 mg/L and <= 2 mg/L, respectively.
      CONCLUSIONS: The results of this study confirm the activity of tedizolid against
      linezolid-resistant staphylococci. This new oxazolidinone could have an important
      role as a potential therapeutic agent against multidrug-resistant staphylococci.

PMID- 21954459
TI  - Impact of antiretroviral therapy on the variability of the HCV NS5B polymerase in
      HIV/HCV co-infected patients.
AB  - OBJECTIVES: Assessment of the impact of antiretroviral drugs on the variability
      of hepatitis C virus (HCV) NS5B polymerase in HIV/HCV co-infected individuals.
      METHODS: HCV NS5B polymerase was sequenced from plasma at baseline and at the end
      of follow-up in HIV/HCV co-infected individuals on a stable antiretroviral
      regimen seen at two outpatient clinics for at least 2 years. The presence of
      mutations associated with drug resistance to experimental HCV polymerase
      inhibitors was examined. RESULTS: Sixty-one HIV/HCV co-infected patients (34% HCV
      1a, 25% HCV-1b, 18% HCV-3 and 23% HCV-4) were analysed. The mean time on
      antiretroviral therapy was 52 months. All patients received HIV nucleoside
      analogues; 66% along with non-nucleoside analogues. The median HCV RNA was 6.1
      log at baseline and 6 log IU/mL at the end of follow-up. The median HIV RNA was
      4.4 log at baseline and 1.5 log copies/mL at the end of follow-up. No evidence of
      selection of NS5B polymerase inhibitor resistance mutations was seen when
      comparing samples collected at baseline and at the end of follow-up from the same
      individuals. All NS5B sequences from HCV-1a and HCV-3 showed V499A, associated
      with resistance to HCV non-nucleoside site-1 inhibitors (NNI-1). In addition, HCV
      3 showed I482L, associated with resistance to NNI-2, and HCV-4 showed M414L,
      I482L and V499A, associated with resistance to NNI-3, 2 and 1, respectively. Two
      HCV-1b patients showed C316N, related with resistance to NNI-4. CONCLUSIONS: The
      use of antiretroviral drugs does not increase the rate of primary drug resistance
      mutations to HCV NS5B polymerase inhibitors in HIV/HCV co-infected patients.
      However, natural polymorphisms associated with reduced susceptibility to some HCV
      NNIs are common, particularly in HCV variants other than HCV-1b.

PMID- 21954460
TI  - The basic helix-loop-helix transcription factor MYC2 directly represses PLETHORA
      expression during jasmonate-mediated modulation of the root stem cell niche in
      Arabidopsis.
AB  - The root stem cell niche, which in the Arabidopsis thaliana root meristem is an
      area of four mitotically inactive quiescent cells (QCs) and the surrounding
      mitotically active stem cells, is critical for root development and growth. We
      report here that during jasmonate-induced inhibition of primary root growth,
      jasmonate reduces root meristem activity and leads to irregular QC division and
      columella stem cell differentiation. Consistently, jasmonate reduces the
      expression levels of the AP2-domain transcription factors PLETHORA1 (PLT1) and
      PLT2, which form a developmentally instructive protein gradient and mediate auxin
      induced regulation of stem cell niche maintenance. Not surprisingly, the effects
      of jasmonate on root stem cell niche maintenance and PLT expression require the
      functioning of MYC2/JASMONATE INSENSITIVE1, a basic helix-loop-helix
      transcription factor that involves versatile aspects of jasmonate-regulated gene
      expression. Gel shift and chromatin immunoprecipitation experiments reveal that
      MYC2 directly binds the promoters of PLT1 and PLT2 and represses their
      expression. We propose that MYC2-mediated repression of PLT expression integrates
      jasmonate action into the auxin pathway in regulating root meristem activity and
      stem cell niche maintenance. This study illustrates a molecular framework for
      jasmonate-induced inhibition of root growth through interaction with the growth
      regulator auxin.

PMID- 21954461
TI  - CFL1, a WW domain protein, regulates cuticle development by modulating the
      function of HDG1, a class IV homeodomain transcription factor, in rice and
      Arabidopsis.
AB  - Plants have a chemically heterogeneous lipophilic layer, the cuticle, which
      protects them from biotic and abiotic stresses. The mechanisms that regulate
      cuticle development are poorly understood. We identified a rice (Oryza sativa)
      dominant curly leaf mutant, curly flag leaf1 (cfl1), and cloned CFL1, which
      encodes a WW domain protein. We overexpressed both rice and Arabidopsis CFL1 in
      Arabidopsis thaliana; these transgenic plants showed severely impaired cuticle
      development, similar to that in cfl1 rice. Reduced expression of At CFL1 resulted
      in reinforcement of cuticle structure. At CFL1 was predominantly expressed in
      specialized epidermal cells and in regions where dehiscence and abscission occur.
      Biochemical evidence showed that At CFL1 interacts with HDG1, a class IV
      homeodomain-leucine zipper transcription factor. Suppression of HDG1 function
      resulted in similar defective cuticle phenotypes in wild-type Arabidopsis but
      much alleviated phenotypes in At cfl1-1 mutants. The expression of two cuticle
      development-associated genes, BDG and FDH, was downregulated in At CFL1
      overexpressor and HDG1 suppression plants. HDG1 binds to the cis-element L1 box,
      which exists in the regulatory regions of BDG and FDH. Our results suggest that
      rice and Arabidopsis CFL1 negatively regulate cuticle development by affecting
      the function of HDG1, which regulates the downstream genes BDG and FDH.

PMID- 21954462
TI  - Genetics, evolution, and adaptive significance of the selfing syndrome in the
      genus Capsella.
AB  - The change from outbreeding to selfing is one of the most frequent evolutionary
      transitions in flowering plants. It is often accompanied by characteristic
      morphological and functional changes to the flowers (the selfing syndrome),
      including reduced flower size and opening. Little is known about the
      developmental and genetic basis of the selfing syndrome, as well as its adaptive
      significance. Here, we address these issues using the two closely related species
      Capsella grandiflora (the ancestral outbreeder) and red shepherd's purse
      (Capsella rubella, the derived selfer). In C. rubella, petal size has been
      decreased by shortening the period of proliferative growth. Using interspecific
      recombinant inbred lines, we show that differences in petal size and flower
      opening between the two species each have a complex genetic basis involving
      allelic differences at multiple loci. An intraspecific cross within C. rubella
      suggests that flower size and opening have been decreased in the C. rubella
      lineage before its extensive geographical spread. Lastly, by generating plants
      that likely resemble the earliest ancestors of the C. rubella lineage, we provide
      evidence that evolution of the selfing syndrome was at least partly driven by
      selection for efficient self-pollination. Thus, our studies pave the way for a
      molecular dissection of selfing-syndrome evolution.

PMID- 21954463
TI  - Salt stress-induced disassembly of Arabidopsis cortical microtubule arrays
      involves 26S proteasome-dependent degradation of SPIRAL1.
AB  - The dynamic instability of cortical microtubules (MTs) (i.e., their ability to
      rapidly alternate between phases of growth and shrinkage) plays an essential role
      in plant growth and development. In addition, recent studies have revealed a
      pivotal role for dynamic instability in the response to salt stress conditions.
      The salt stress response includes a rapid depolymerization of MTs followed by the
      formation of a new MT network that is believed to be better suited for surviving
      high salinity. Although this initial depolymerization response is essential for
      the adaptation to salt stress, the underlying molecular mechanism has remained
      largely unknown. Here, we show that the MT-associated protein SPIRAL1 (SPR1)
      plays a key role in salt stress-induced MT disassembly. SPR1, a microtubule
      stabilizing protein, is degraded by the 26S proteasome, and its degradation rate
      is accelerated in response to high salinity. We show that accelerated SPR1
      degradation is required for a fast MT disassembly response to salt stress and for
      salt stress tolerance.

PMID- 21954465
TI  - Functional analysis of Arabidopsis NHX antiporters: the role of the vacuole in
      cellular turgor and growth.

PMID- 21954464
TI  - POD1 regulates pollen tube guidance in response to micropylar female signaling
      and acts in early embryo patterning in Arabidopsis.
AB  - The pollen tube germinates from pollen and, during its migration, it perceives
      and responds to guidance cues from maternal tissue and from the female
      gametophyte. The putative female cues have recently been identified, but how the
      pollen tube responds to these signals remains to be unveiled. In a genetic screen
      for male determinants of the pollen tube response, we identified the pollen
      defective in guidance1 (pod1) mutant, in which the pollen tubes fail to target
      the female gametophyte. POD1 encodes a conserved protein of unknown function and
      is essential for positioning and orienting the cell division plane during early
      embryo development. Here, we demonstrate that POD1 is an endoplasmic reticulum
      (ER) luminal protein involved in ER protein retention. Further analysis shows
      that POD1 interacts with the Ca(2+) binding ER chaperone CALRETICULIN3 (CRT3), a
      protein in charge of folding of membrane receptors. We propose that POD1
      modulates the activity of CRT3 or other ER resident factors to control the
      folding of proteins, such as membrane proteins in the ER. By this mechanism, POD1
      may regulate the pollen tube response to signals from the female tissues during
      pollen tube guidance and early embryo patterning in Arabidopsis thaliana.

PMID- 21954466
TI  - A sense of self: exploring the selfing syndrome in capsella.

PMID- 21954468
TI  - The cover. Still life with yellow roses.

PMID- 21954467
TI  - The Arabidopsis Na+/H+ antiporters NHX1 and NHX2 control vacuolar pH and K+
      homeostasis to regulate growth, flower development, and reproduction.
AB  - Intracellular Na(+)/H(+) (NHX) antiporters have important roles in cellular pH
      and Na(+), K(+) homeostasis. The six Arabidopsis thaliana intracellular NHX
      members are divided into two groups, endosomal (NHX5 and NHX6) and vacuolar (NHX1
      to NHX4). Of the vacuolar members, NHX1 has been characterized functionally, but
      the remaining members have largely unknown roles. Using reverse genetics, we show
      that, unlike the single knockouts nhx1 or nhx2, the double knockout nhx1 nhx2 had
      significantly reduced growth, smaller cells, shorter hypocotyls in etiolated
      seedlings and abnormal stamens in mature flowers. Filaments of nhx1 nhx2 did not
      elongate and lacked the ability to dehisce and release pollen, resulting in a
      near lack of silique formation. Pollen viability and germination was not
      affected. Quantification of vacuolar pH and intravacuolar K(+) concentrations
      indicated that nhx1 nhx2 vacuoles were more acidic and accumulated only 30% of
      the wild-type K(+) concentration, highlighting the roles of NHX1 and NHX2 in
      mediating vacuolar K(+)/H(+) exchange. Growth under added Na(+), but not K(+),
      partly rescued the flower and growth phenotypes. Our results demonstrate the
      roles of NHX1 and NHX2 in regulating intravacuolar K(+) and pH, which are
      essential to cell expansion and flower development.

PMID- 21954469
TI  - A piece of my mind. In the still of the night.

PMID- 21954470
TI  - Questions about spine fusion product prompt a new process for reviewing data.

PMID- 21954471
TI  - Joint guideline focuses on COPD care.

PMID- 21954472
TI  - Cancer care accreditation standards: improve quality and help patients cope.

PMID- 21954473
TI  - Survival after bariatric surgery among high-risk patients.

PMID- 21954474
TI  - Ambulance diversion and survival among patients with acute myocardial infarction.

PMID- 21954475
TI  - Statin therapy dose and risk of new-onset diabetes.

PMID- 21954476
TI  - Hospitalization for acute heart failure syndromes.

PMID- 21954477
TI  - Operator experience and carotid stenting outcomes in Medicare beneficiaries.
AB  - CONTEXT: Although the efficacy of carotid stenting has been established in
      clinical trials, outcomes of the procedure based on operator experience are less
      certain in clinical practice. OBJECTIVE: To assess association between outcomes
      and 2 measures of operator experience: annual volume and experience at the time
      of the procedure among new operators who first performed carotid stenting after a
      national coverage decision by the Centers for Medicare & Medicaid Services (CMS).
      DESIGN, SETTING, AND PATIENTS: Observational study using administrative data on
      fee-for-service Medicare beneficiaries aged 65 years or older undergoing carotid
      stenting between 2005 and 2007. MAIN OUTCOME MEASURE: Thirty-day mortality
      stratified by very low, low, medium, and high annual operator volumes (<6, 6-11,
      12-23, and >=24 procedures per year, respectively) and treatment early vs late
      during a new operator's experience (1st to 11th procedure and 12th procedure or
      higher). RESULTS: During the study period, 24,701 procedures were performed by
      2339 operators. Of these, 11,846 were performed by 1792 new operators who first
      performed carotid stenting after the CMS national coverage decision. Overall, 30
      day mortality was 1.9% (n = 461) and rate of failure to use an embolic protection
      device was 4.8% (n = 1173). The median annual operator volume among Medicare
      beneficiaries was 3.0 per year (interquartile range, 1.4-6.5) and 11.6% of
      operators performed 12 or more procedures per year during the study period.
      Observed 30-day mortality was higher among patients treated by operators with
      lower annual volumes (2.5% [95% CI, 2.1%-2.9%], 1.9% [95% CI, 1.6%-2.3%], 1.6%
      [95% CI, 1.3%-1.9%], and 1.4% [95% CI, 1.1%-1.7%] across the 4 categories; P <
      .001) and among patients treated early (2.3%; 95% CI, 2.0%-2.7%) vs late (1.4%;
      95% CI, 1.1%-1.9%; P < .001) during a new operator's experience. After
      multivariable adjustment, patients treated by very low-volume operators had a
      higher risk of 30-day mortality compared with patients treated by high-volume
      operators (adjusted odds ratio, 1.9; 95% CI, 1.4-2.7; P < .001). Similarly, we
      found a higher risk of 30-day mortality in patients treated early vs late during
      a new operator's experience (adjusted odds ratio, 1.7; 95% CI, 1.2-2.4; P =
      .001). CONCLUSION: Among older patients undergoing carotid stenting, lower annual
      operator volume and early experience are associated with increased 30-day
      mortality.

PMID- 21954479
TI  - Sex-specific prevalence of adenomas, advanced adenomas, and colorectal cancer in
      individuals undergoing screening colonoscopy.
AB  - CONTEXT: Although some studies have shown that men are at greater age-specific
      risk for advanced colorectal neoplasia than women, the age for referring patients
      to screening colonoscopy is independent of sex and usually recommended to be 50
      years. OBJECTIVE: To determine and compare the prevalence and number needed to
      screen (NNS) for adenomas, advanced adenomas (AAs), and colorectal carcinomas
      (CRCs) for different age groups in men and women. DESIGN, SETTING, AND PATIENTS:
      Cohort study of 44,350 participants in a national screening colonoscopy program
      over a 4-year period (2007 to 2010) in Austria. MAIN OUTCOME MEASURES: Prevalence
      and NNS of adenomas, AAs, and CRCs in different age groups for men and women.
      RESULTS: The median ages were 60.7 years (interquartile range [IQR], 54.5-67.5
      years) for women and 60.6 years (IQR, 54.3-67.6 years) for men, and the sex ratio
      was nearly identical (51.0% [22,598] vs 49.0% [21,572]). Adenomas were found in
      19.7% of individuals screened (95% CI, 19.3%-20.1%; n = 8743), AAs in 6.3% (95%
      CI, 6.1%-6.5%; n = 2781), and CRCs in 1.1% (95% CI, 1.0%-1.2%; n = 491); NNS were
      5.1 (95% CI, 5.0-5.2), 15.9 (95% CI, 15.4-16.5), and 90.9 (95% CI, 83.3-100.0),
      respectively. Male sex was significantly associated with a higher prevalence of
      adenomas (24.9% [95% CI, 24.3%-25.4%] vs 14.8% [95% CI, 14.3%-15.2%]; P < .001;
      unadjusted odds ratio [OR], 1.9 [95% CI, 1.8-2.0]), AAs (8.0% [95% CI, 7.6%-8.3%]
      vs 4.7% [95% CI, 4.4%-4.9%]; P < .001; unadjusted OR, 1.8 [95% CI, 1.6-1.9]), and
      CRCs (1.5% [95% CI, 1.3%-1.7%] vs 0.7% [95% CI, 0.6%-0.9%]; P < .001; unadjusted
      OR, 2.1 [95% CI, 1.7-2.5]). The prevalence of AAs in 50- to 54-year-old
      individuals was 5.0% (95% CI, 4.4%-5.6%) in men but 2.9% (95% CI, 2.5%-3.4%) in
      women (adjusted P = .001); the NNS in men was 20 (95% CI, 17.8-22.6) vs 34 in
      women (95% CI, 29.1-40; adjusted P = .001). There was no statistical significance
      between the prevalence and NNS of AAs in men aged 45 to 49 years compared with
      women aged 55 to 59 years (3.8% [95% CI, 2.3%-6.1%] vs 3.9% [95% CI, 3.3%-4.5%]
      and 26.1 [95% CI, 16.5-44.4] vs 26 [95% CI, 22.5-30.2]; P = .99). CONCLUSION:
      Among a cohort of Austrian individuals undergoing screening colonoscopy, the
      prevalence and NNS of AAs were comparable between men aged 45 to 49 years and
      women aged 55 to 59 years.

PMID- 21954478
TI  - Effect of increasing doses of saw palmetto extract on lower urinary tract
      symptoms: a randomized trial.
AB  - CONTEXT: Saw palmetto fruit extracts are widely used for treating lower urinary
      tract symptoms attributed to benign prostatic hyperplasia (BPH); however, recent
      clinical trials have questioned their efficacy, at least at standard doses (320
      mg/d). OBJECTIVE: To determine the effect of saw palmetto extract (Serenoa
      repens, from saw palmetto berries) at up to 3 times the standard dose on lower
      urinary tract symptoms attributed to BPH. DESIGN, SETTING, AND PARTICIPANTS: A
      double-blind, multicenter, placebo-controlled randomized trial at 11 North
      American clinical sites conducted between June 5, 2008, and October 10, 2010, of
      369 men aged 45 years or older, with a peak urinary flow rate of at least 4 mL/s,
      an American Urological Association Symptom Index (AUASI) score of between 8 and
      24 at 2 screening visits, and no exclusions. INTERVENTIONS: One, 2, and then 3
      doses (320 mg/d) of saw palmetto extract or placebo, with dose increases at 24
      and 48 weeks. MAIN OUTCOME MEASURES: Difference in AUASI score between baseline
      and 72 weeks. Secondary outcomes included measures of urinary bother, nocturia,
      peak uroflow, postvoid residual volume, prostate-specific antigen level,
      participants' global assessments, and indices of sexual function, continence,
      sleep quality, and prostatitis symptoms. RESULTS: Between baseline and 72 weeks,
      mean AUASI scores decreased from 14.42 to 12.22 points (-2.20 points; 95% CI, 
      3.04 to -1.36) [corrected]with saw palmetto extract and from 14.69 to 11.70
      points (-2.99 points; 95% CI, -3.81 to -2.17) with placebo. The group mean
      difference in AUASI score change from baseline to 72 weeks between the saw
      palmetto extract and placebo groups was 0.79 points favoring placebo (upper bound
      of the 1-sided 95% CI most favorable to saw palmetto extract was 1.77 points, 1
      sided P = .91). Saw palmetto extract was no more effective than placebo for any
      secondary outcome. No clearly attributable adverse effects were identified.
      CONCLUSION: Increasing doses of a saw palmetto fruit extract did not reduce lower
      urinary tract symptoms more than placebo. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00603304.

PMID- 21954480
TI  - Efficacy and comparative effectiveness of atypical antipsychotic medications for
      off-label uses in adults: a systematic review and meta-analysis.
AB  - CONTEXT: Atypical antipsychotic medications are commonly used for off-label
      conditions such as agitation in dementia, anxiety, and obsessive-compulsive
      disorder. OBJECTIVE: To perform a systematic review on the efficacy and safety of
      atypical antipsychotic medications for use in conditions lacking approval for
      labeling and marketing by the US Food and Drug Administration. DATA SOURCES AND
      STUDY SELECTION: Relevant studies published in the English language were
      identified by searches of 6 databases (PubMed, EMBASE, CINAHL, PsycInfo, Cochrane
      DARE, and CENTRAL) from inception through May 2011. Controlled trials comparing
      an atypical antipsychotic medication (risperidone, olanzapine, quetiapine,
      aripiprazole, ziprasidone, asenapine, iloperidone, or paliperidone) with placebo,
      another atypical antipsychotic medication, or other pharmacotherapy for adult off
      label conditions were included. Observational studies with sample sizes of
      greater than 1000 patients were included to assess adverse events. DATA
      EXTRACTION: Independent article review and study quality assessment by 2
      investigators. DATA SYNTHESIS: Of 12 228 citations identified, 162 contributed
      data to the efficacy review. Among 14 placebo-controlled trials of elderly
      patients with dementia reporting a total global outcome score that includes
      symptoms such as psychosis, mood alterations, and aggression, small but
      statistically significant effects sizes ranging from 0.12 and 0.20 were observed
      for aripiprazole, olanzapine, and risperidone. For generalized anxiety disorder,
      a pooled analysis of 3 trials showed that quetiapine was associated with a 26%
      greater likelihood of a favorable response (defined as at least 50% improvement
      on the Hamilton Anxiety Scale) compared with placebo. For obsessive-compulsive
      disorder, risperidone was associated with a 3.9-fold greater likelihood of a
      favorable response (defined as a 25% improvement on the Yale-Brown Obsessive
      Compulsive Scale) compared with placebo. In elderly patients, adverse events
      included an increased risk of death (number needed to harm [NNH] = 87), stroke
      (NNH = 53 for risperidone), extrapyramidal symptoms (NNH = 10 for olanzapine; NNH
      = 20 for risperidone), and urinary tract symptoms (NNH range = 16-36). In
      nonelderly adults, adverse events included weight gain (particularly with
      olanzapine), fatigue, sedation, akathisia (for aripiprazole), and extrapyramidal
      symptoms. CONCLUSIONS: Benefits and harms vary among atypical antipsychotic
      medications for off-label use. For global behavioral symptom scores associated
      with dementia in elderly patients, small but statistically significant benefits
      were observed for aripiprazole, olanzapine, and risperidone. Quetiapine was
      associated with benefits in the treatment of generalized anxiety disorder, and
      risperidone was associated with benefits in the treatment of obsessive-compulsive
      disorder; however, adverse events were common.

PMID- 21954481
TI  - The Supplemental Nutrition Assistance Program, soda, and USDA policy: who
      benefits?

PMID- 21954482
TI  - Carotid stenting at the crossroads: practice makes perfect, but some may be
      practicing too much (and not enough).

PMID- 21954483
TI  - JAMA patient page. Local anesthesia.

PMID- 21954484
TI  - The impact of childhood experiences and family members outside the household on
      residential environment choices.
AB  - Choices of urban, suburban or rural residential environments have often been
      studied from a life-course perspective. In this paper, an examination is made of
      the influence of childhood experiences and of residential environment choices of
      family members outside the household. It is argued that socialisation, location
      specific capital and the wish to maintain close family ties may result in living
      in a similar residential environment later in life and in similar environments to
      siblings and parents. Results of multinomial logistic regression analyses of data
      from the Netherlands Kinship Panel Study show that the residential environment
      during childhood is indeed strongly associated with the current residential
      environment. Moreover, individuals show a strong similarity to their parents and
      siblings in their residential environment, even after accounting for residential
      inertia and return migration.

PMID- 21954485
TI  - Comparative approaches to measuring food access in urban areas: the case of
      Portland, Oregon.
AB  - GIS methods are used to construct measures of food access for neighbourhoods in
      the Portland, Oregon, US metropolitan area and the sensitivity of such measures
      to methodological variation is examined. The level of aggregation of data inputs
      is varied and the effect of using both Euclidean and street network distances is
      tested. It is found that, regardless of the level of geographical disaggregation,
      distance-based measures generate approximately the same conclusions about the
      distribution of food access in the area. It is also found that, while the
      relationship between street network and Euclidean distances varies with
      population density, measures computed with either construct generate the same
      relative patterns of food access. These findings suggest that results from food
      access studies employing disparate methodologies can often be compared.

PMID- 21954487
TI  - Evangelicalism and the early vegetarian movement in Britain c.1847-1860.
AB  - This article explores the complex inter-relationship between evangelicalism and
      the formation of an organised vegetarian movement in Britain in the period 1847
      1860. As well as adding insight into existing historical research into the diet,
      I will comment on the potential of evangelicalism's influence to reach into
      various areas of society, a claim that has often been contested in the existing
      historiography. I will explore the manner by which religious belief interacted
      with medico-scientific views pertaining to diet; and how it penetrated views on
      the role of diet to family life.

PMID- 21954486
TI  - "Near and far": social distancing in domiciled characterisations of homeless
      people.
AB  - For domiciled individuals, homeless people provide a disturbing reminder that all
      is not right with the world. Reactions to seeing homeless people frequently
      encompass repulsion, discomfort, sympathy and sometimes futility. This paper
      considers domiciled constructions of homeless people drawn from interviews with
      16 participants recruited in the central business district of a New Zealand city.
      It documents how, when trying to make sense of this complex social problem,
      domiciled people draw on shared characterizations of homeless people. The concept
      of "social distance" is used to interrogate the shifting and sometimes
      incongruous reactions evident in participant accounts. "Social distancing" is
      conceptualised as a dynamic communal practice existing in interactions between
      human beings and reflected in the ways that domiciled people talk about their
      experiences with homeless individuals.

PMID- 21954488
TI  - What was uniform about the fin-de-siecle sailor suit?
AB  - The sailor suits widely worn by children in late-nineteenth-century Britain have
      been interpreted at the time, and since, as expressions of an Imperial ethos.
      Yet, a closer examination of the ways that these garments were produced by mass
      manufacturers, mediated by advertisers and fashion advisors and consumed by
      families makes us question this characterization. Manufacturers interpreted
      sailor suits not as unchanging uniforms but as fashion items responding to
      seasonal changes. Consumers used them to assert social identities and social
      distinctions, selecting from the multiple variants available. Cultural
      commentators described sailor suits as emulating Royal practice-but also as
      'common' and to be avoided. A close analysis of large samples of images and texts
      from the period 1870-1900 reveals how these different meanings overlapped, making
      the fin-de-siecle sailor suit a garment that undermines many of our assumptions.

PMID- 21954489
TI  - The illicit consumption of military uniforms in Britain, 1914-1918.
AB  - Focusing on the British home front during the First World War, this article
      explores civilians' motives for acquiring and wearing military garments and
      accoutrements to which they were not entitled. It suggests that uniforms could be
      donned either to avoid the attentions of recruiting sergeants, or to perpetrate
      criminal deceptions. That said, individuals did not always wear illicit uniforms
      in order to 'disguise' their civilian identity. Rather, many men claimed a sense
      of entitlement to such items, either on the basis of previous war service, or,
      more often, on the basis of their contributions to the war effort on the home
      front. The acquisition of military items could also reflect men's roles as
      consumers: for many civilians, acquiring and wearing the newly glamorous uniforms
      was a consumer choice that could also open the door to further leisure and
      consumer opportunities. Overall, illicitly wearing military items undermined the
      uniform's link with service and sacrifice on the battle fronts: it allowed
      individuals to assume the appearance of combatants or to assert their patriotic
      identities without actually exposing themselves to military duties or dangers. It
      also reflected (some) men's continued perception of themselves as consumers,
      keen, even in wartime, to adopt what they saw as the most desirable sartorial
      option.

PMID- 21954490
TI  - Traditional ecologies of the opium poppy and oral history in rural Turkey.
AB  - Cultivated in the Eastern Mediterranean region for millennia, the opium poppy
      (Papaver somniferum) was profoundly significant in the economies, ecologies,
      cultures, and diets of the peoples of many towns and villages of rural Anatolia.
      When the United States compelled Turkey to eradicate cultivation of the plant in
      the early 1970s in order to diminish the flow of heroin into America, farmers
      were obliged to deal with not only changes in their incomes but also profound
      changes in their relationships with the land and the state. Although Turkish
      officials later allowed production to resume in a highly controlled manner for
      pharmaceutical purposes, significant socioeconomic and ecological dimensions of
      Turkey's poppy-growing communities were forever changed. Interviewing now-retired
      poppy farmers, I employ oral history as my primary source of historical evidence
      to reconstruct these past ecologies and associated social relationships and to
      give voice to the informants.

PMID- 21954491
TI  - Bites, nibbles, sips and puffs: new exotic goods in Norway in the 18th and the
      first half of the 19th century.
AB  - The slow but significant changes in the material culture of European households
      that took place in the pre-industrial period are visible in several ways, such as
      in the changing patterns of housing, furnishing and clothing which have been
      illustrated in several studies. However, most of these studies focus on the pre
      industrial economic leaders, often ignoring the changes taking place on the
      margins of the economic growth centres. This article seeks to rectify this by
      looking at changes in the material culture in one such 'marginal' country, namely
      Norway. The goods focused upon in this case are sugar, tobacco and coffee, which
      are often termed as exotic goods. These were new commodities in the 18th century
      and precisely because of their novelty and foreign origin, it is in many cases
      possible to trace how they spread in rural society, as well as how they impacted
      it. The emphasis has been put on rural areas for the simple reason that this was
      where the overall majority of Norwegians lived at the time.

PMID- 21954492
TI  - "A nation's need-good and well trained mothers": gender, charity, and the new
      urban south.

PMID- 21954493
TI  - The geography of pornography: neighborhood feminism and the battle against "dirty
      bookstores" in Minneapolis.

PMID- 21954494
TI  - [Progress in hearing aids and cochlear implants: a user's viewpoint].

PMID- 21954495
TI  - [Balloon sinuplasty].

PMID- 21954496
TI  - Gender and caring in South Africa. Some lessons from history.

PMID- 21954497
TI  - Couching for cataract: advanced medical achievements of China in 1976?
AB  - Cataracts have been a common disease in China for centuries. As early as the Tang
      dynasty, physicians of Chinese medicine had developed 'jin pi shu', a method of
      couching, to cure the disease. In 1976, a new method, invented by Tang Youzhi,
      was acknowledged as one of the most advanced medical achievements in communist
      China. This paper explores the significance of Tang's method for Mao Zedong's
      China. Tang's method achieved two goals set by Chairman Mao for medical and
      health policies: to serve rural China and to integrate Chinese and Western
      medicine.

PMID- 21954498
TI  - Migrants, urbanites & health care on the Witwatersrand, c 1930-1950.

PMID- 21954499
TI  - Lethal differences: a short history of the concepts of wealth and poverty in
      Danish epidemiological writings, 1858-1914.
AB  - Through a study of the history of the concepts of wealth and poverty, this paper
      investigates the onset of a tradition in the conceptual architecture of
      epidemiological research concerning social differences in mortality rates from
      1858 to 1914. It raises the question as to what the concepts of wealth and
      poverty meant to those who used them and what objects of interventions the
      conceptual architecture surrounding the concepts enabled the researchers to
      create. It argues that a transition began in the late 19th century in which an
      important framework for the understanding of causal relations behind the
      mortality patterns changed and that this change in turn influenced the scope of
      what was conceived as relevant objects of intervention.

PMID- 21954500
TI  - [Voice surgery department and rehabilitation].

PMID- 21954501
TI  - Labour before a caesarean section and the morphology of the lower uterine segment
      in the next pregnancy.

PMID- 21954502
TI  - Making a case for abortion curriculum reform: a knowledge-assessment survey of
      undergraduate medical students.

PMID- 21954503
TI  - Busyness, the dental workforce and endodontics.

PMID- 21954504
TI  - The psychologization of humanitarian aid: skimming the battlefield and the
      disaster zone.
AB  - Humanitarian aid's psycho-therapeutic turn in the 1990s was mirrored by the
      increasing emotionalization and subjectivation of fund-raising campaigns. In
      order to grasp the depth of this interconnectedness, this article argues that in
      both cases what we see is the post-Fordist production paradigm at work; namely,
      as Hardt and Negri put it, the direct production of subjectivity and social
      relations. To explore this, the therapeutic and mental health approach in
      humanitarian aid is juxtaposed with the more general phenomenon of
      psychologization. This allows us to see that the psychologized production of
      subjectivity has a problematic waste-product as it reduces the human to 'Homo
      sacer', to use Giorgi Agamben's term. Drawing out a double matrix of a de
      psychologizing psychologization connected to a politicizing de-politicization, it
      will further become possible to understand psycho-therapeutic humanitarianism as
      a case of how, in these times of globalization, psychology, subjectivity and
      money are all interrelated.

PMID- 21954505
TI  - Journal metrics.

PMID- 21954506
TI  - Adenosine for maternal supraventricular tachycardia and preterm delivery.

PMID- 21954507
TI  - Tranquil estuary.

PMID- 21954508
TI  - [Poisonings reported to the Poison Control Center during 2010].

PMID- 21954509
TI  - Methemoglobinemia: a systematic review of the pathophysiology, detection, and
      treatment.
AB  - Methemoglobin is the oxidized form of hemoglobin which does not bind to oxygen
      efficiently. An increased level of methemoglobin can be attributed to congenital
      enzymatic defects, alterations in the hemoglobin molecule, or as a result of
      medications and toxins. The main clinical characteristic of the disease include
      cyanosis which is unresponsive to oxygen therapy and blood that is chocolate
      color when drawn. Co-oximetry is the gold standard for diagnosis but arterial
      blood gas paired with pulse oximetry and serum methemoglobin levels can confirm
      the diagnosis clinically. Treatment is aimed at removal of the offending agent,
      if medication induced, and is directed at aggressive oxygen therapy and treatment
      with the antidote, methylene blue.

PMID- 21954510
TI  - Licorice: a patient's shocking presentation.

PMID- 21954511
TI  - Just who are we working for?

PMID- 21954512
TI  - Indacaterol. A long-acting beta-2 agonist, no advantages in COPD.
AB  - In patients with chronic obstructive pulmonary disease (COPD), bronchodilator
      drugs have only modest symptomatic efficacy. There is no evidence that they slow
      disease progression. A short-acting beta-2 agonist such as salbutamol is the
      first-choice treatment, used either on demand or on a regular basis. Long-acting
      beta2 agonists are an option for patients with nocturnal symptoms. Indacaterol is
      a long-acting beta-2 agonist that is inhaled once a day. Indacaterol has not been
      compared with a short-acting beta-2 agonist. Clinical evaluation is based on 4
      double-blind randomised placebo-controlled trials, 3 of which also included a
      group treated with another long-acting bronchodilator (formoterol, salmeterol or
      tiotropium. The symptomatic efficacy of indacaterol was only modest, and similar
      to that of other long-acting bronchodilators. Indacaterol has the known adverse
      effect profile of beta-2 agonists. Some adverse effects seem to be more frequent
      than with other long-acting bronchodilators, including post-inhalation cough,
      hyperglycaemia, respiratory tract infections, and possibly cardiac disorders.
      There is no evidence that once-daily inhalation has any advantages over twice
      daily inhalation, even in terms of convenience. In addition, as efficacy is
      limited, there is a risk that patients will use the drug more frequently,
      resulting in additional adverse effects. The nebulizer used to inhale the powder
      in the capsules is similar to the one provided with Foradil (formoterol. In
      practice, indacaterol offers no therapeutic advantage over existing treatments
      for patients with COPD. It is better to use the best-documented drugs and, if
      necessary, to add non-drug measures. Eliminating exposure to toxic agents,
      especially tobacco smoke, remains the only treatment with a proven benefit on the
      course of COPD.

PMID- 21954514
TI  - Inn common stem: -ciclovir.

PMID- 21954513
TI  - Aciclovir + hydrocortisone. Herpes labialis: a topical antiviral drug perhaps,
      but not a steroid.
AB  - Management of episodes of herpes labialis (cold sores) in otherwise healthy
      individuals is mainly based on hygiene measures intended to avoid transmitting
      the virus. At best, topical treatment with aciclovir, an antiviral drug, simply
      reduces the duration of the episode. A cream containing 5% aciclovir and 1%
      hydrocortisone has been authorised in France for symptomatic treatment of herpes
      labialis in adults and adolescents 12 years of age and older. In a double-blind
      randomised trial comparing the combination versus topical aciclovir alone in 1443
      adults, the cream did not significantly reduce the number of patients whose
      lesions became ulcerated, or the duration of the episode. In another comparative
      double-blind randomised trial in 107 immunocompromised patients, the efficacy of
      the aciclovir and hydrocortisone combination did not differ from that of
      aciclovir alone. Whatever the mode of administration, corticosteroids might
      aggravate infections. In clinical trials involving immunocompetent adults or
      adolescents, most adverse effects associated with the hydrocortisone + aciclovir
      combination were local and mild. Hypersensitivity reactions are possible,
      however. This combination should be avoided during pregnancy, given the mild
      nature of herpes labialis and concerns over the risks of corticosteroids for the
      unborn child. In practice, there is no firm evidence that the aciclovir +
      hydrocortisone combination is more effective than aciclovir alone. Given the
      inherent risks associated with hydrocortisone, it is better to recommend simple
      hygiene measures and, possibly, aciclovir alone.

PMID- 21954515
TI  - Mesalazine. Now authorised for children, but no suitable form.

PMID- 21954516
TI  - Skin-lightening cosmetics: frequent, potentially severe adverse effects.
AB  - Skin-lightening cosmetics are used by many women and men around the world. The
      products contain a variety of substances, which are often unknown to the users.
      Most of these products include topical corticosteroids, hydroquinone and mercury
      salts. Many other substances may be added. Several surveys and cohort studies,
      including several thousand individuals, have shown that regular application of
      skin-lightening cosmetics to large surface areas can have irreversible cutaneous
      adverse effects, such as patchy hyper- or hypopigmentation, skin atrophy, stretch
      marks and delayed wound healing, and can also mask or, on the contrary, promote
      or reactivate skin infections. Cases of skin cancer have been attributed to skin
      lightening cosmetics. A Senegalese cohort study of 147 women showed a
      statistically significant increase in the risk of hypertension and diabetes
      linked to the use of skin-lightening agents. Other systemic adverse effects
      attributed to skin-lightening cosmetics include Cushing's syndrome, adrenal
      insufficiency, nephrotic syndrome, neurological disorders, and ocular disorders.
      Hypersensitivity reactions, including anaphylaxis, have also been attributed to
      these products. Many skin-lightening cosmetics contain substances that can harm
      the unborn child. For example, tretinoin is teratogenic while salicylic acid is
      feto-toxic. In practice, users are often unaware of the risk of severe adverse
      effects associated with skin-lightening cosmetics. Users should be informed of
      these adverse effects and encouraged to stop using these products, especially
      when skin disorders appear.

PMID- 21954517
TI  - Adverse effect profile of common components of skin-lightening cosmetics.

PMID- 21954518
TI  - Skin-lightening creams: warn women of child-bearing age about the risks.

PMID- 21954519
TI  - Nonsteroidal anti-inflammatory drugs: add an anti-ulcer drug for patients at high
      risk only. Always limit the dose and duration of treatment with NSAIDs.
AB  - In addition to their cardiac, renal, hepatic, cutaneous and neuropsychological
      adverse effects, nonsteroidal anti-inflammatory drugs (NSAIDs) can have severe
      effects on the entire gastrointestinal tract, including bleeding, perforation and
      occlusion. Which anti-ulcer drugs reduce the risk of the severe gastrointestinal
      adverse effects of NSAIDs, and which patients should receive them? To answer
      these questions, we conducted a review of the literature, using the standard
      Prescrire methodology. The main risk factors for severe gastrointestinal adverse
      effects during NSAID therapy are: a high dose regimen; age over 65 years; a
      history of gastric or duodenal ulcer or gastrointestinal bleeding; heavy use of
      both alcohol and tobacco; and concomitant treatment with a corticosteroid,
      antiplatelet drug, anticoagulant, or selective serotonin reuptake inhibitor
      (SSRI) antidepressant. Gastrointestinal symptoms and ulceration (on endoscopy)
      are poor predictors of severe gastrointestinal reactions. A meta-analysis
      examined randomised placebo-controlled trials of misoprostol in more than 11 000
      patients. The results were mainly based on a large trial including about 9000
      rheumatoid arthritis patients with an average age of 68 years. Misoprostol (400
      microg to 800 microg/day, in 4 doses) prevented about 4 severe gastroduodenal
      events when 1000 patients over 60 years of age were treated for 6 months.
      Diarrhoea and other mild gastrointestinal disorders were frequent. There are no
      randomised trials comparing proton pump inhibitors (PPIs) and histamine H2
      receptor antagonists versus misoprostol or versus placebo therapy for the
      prevention of severe adverse effects associated with NSAIDs. PPIs and H2
      antagonists both reduce the incidence of gastric or duodenal ulceration detected
      by routine endoscopy. A randomised trial compared an H2 antagonist (famotidine)
      versus a PPI (pantoprazole) in 128 patients with an average age of 69 years who
      had a very high risk of serious gastrointestinal adverse effects while taking low
      dose aspirin. After 48 weeks of treatment, pantoprazole was more effective than
      famotidine for the prevention of overt gastrointestinal bleeding. The symptomatic
      effects of PPIs and H2 antagonists may create a false sense of security, leading
      some patients to increase their NSAID use and resulting in a paradoxical increase
      in severe gastrointestinal effects. In practice, anti-ulcer drugs are not
      sufficiently effective to warrant their use by NSAID-treated adults who are not
      at high risk of severe gastrointestinal events. Misoprostol has proven efficacy
      in patients with risk factors for NSAID-induced severe gastroduodenal adverse
      effects, especially patients over 65 years of age, but it also has frequent
      adverse effects and necessitates 4 daily doses. Omeprazole is an alternative when
      the adverse effects or dosing frequency of misoprostol are unacceptable, provided
      patients are warned not to increase their NSAID consumption.

PMID- 21954520
TI  - Rational use of anti-ulcer drugs to prevent serious gastroduodenal adverse
      effects associated with NSAIDS.

PMID- 21954521
TI  - Medical ethics and social justice.

PMID- 21954522
TI  - Does Prescrire's editorial staff have conflicts of interest?

PMID- 21954523
TI  - New end-to-end microvascular anastomosis with geometrically adaptable ends
      technique: an experimental study on rats.
AB  - OBJECTIVE: The aim of this study was to develop an effective arterial anastomosis
      model with a high patency rate and low operation time. We introduced a new end-to
      end microvascular anastomosis with geometrically adaptable ends. METHODOLOGY: In
      this technique, two triangular flaps were prepared at the end of the vessels and
      four stitches applied on the tip of those flaps. During this study, 15 new
      technique anastomoses were compared to 15 conventional 8 stitches anastomoses in
      30 rat femoral arteries. Operating time, patency rates and number of stitches
      with consequential effects on the vessel wall were analyzed statistically. The
      anastomotic patency of both groups was assessed by: (1) in vivo observation using
      the milking test under the operating microscope and (2) flow study using laser
      Doppler ultrasound. Healing was assessed by the light and electron microscopy.
      RESULTS: According to statistical results and compared to the conventional
      method, the new technique was associated with a significant time savings (mean 18
      vs 26 minutes, p < 0.001). The patency rates were equivalent to the conventional
      technique by observation and laser Doppler ultrasound (p > 0.05). Histological
      evaluation of both techniques showed that rats operated with the new technique
      healed faster and with less endothelial damage. CONCLUSIONS: This new
      "Geometrically Adaptable Ends Technique" is faster, easier to perform and a
      reliable method with patency and flow characteristics similar to those of the
      conventional end-to-end anastomoses (Fig. 7, Ref. 20).

PMID- 21954524
TI  - Home care in Slovakia.
AB  - Home nursing care is an important and inseparable part of individual long-term
      healthcare. The need of complex home care in Slovakia has an increasing trend
      both for clients/patients and for healthcare workers. Inquiries show that as many
      as 90% of citizens prefer to have health and social care provided within their
      own home settings. Due to the fact that the number of old people is increasing
      worldwide, including Slovakia, old people will be the only age group with a
      growing number of inhabitants in the nearest future. We should be aware of a
      significant fact that the number of people over 65 years, i.e., of those in need
      of health and social assistance, is continuously expanding and will form the
      largest group. As old age is typically associated with advanced stages of chronic
      diseases requiring treatment in form of follow-up and nursing, the support of
      complex home care development in Slovakia is of great importance. The aim of home
      care is to provide complex care in coordination with ambulatory and institution
      based care as well as with provision of care services. In 2008, the home nursing
      care expenditures in Slovakia amounted to EUR 9.3 million (Tab. 1, Ref. 18).

PMID- 21954525
TI  - Anthropometric risk factors of atherosclerosis: differences between urban and
      rural east-Slovakian children and adolescents.
AB  - OBJECTIVE: To describe selected risk factors of atherosclerosis in probands from
      East Slovakia, namely their regional (urban/rural), gender-related (male/female)
      and age (children/adolescents) differences. BACKGROUND: The development of
      cardiovascular disease at a young age is influenced by anthropometric risk
      factors (obesity and hypertension). PARTICIPANTS: The study population consisted
      of 191 children and adolescents (97 males and 94 females) aged 7-18 from East
      Slovakia region (114 urban and 77 rural participants). METHODS: Anthropometric
      measurements including weight, height, waist and hip circumference and skinfold
      thickness (subscapular, tricipital) were used to calculate the sum of body fat,
      body mass index and waist-to-hip ratio. Measured blood pressure was used to
      classify hypertension. RESULTS: Higher means of waist-to-hip ratio and higher
      presence of obesity, hypertension, positive cardiovascular disease family history
      and poor lifestyle factors (cigarette smoking, physical inactivity, stress and
      low socioeconomic status) were found in urban children and adolescents compared
      to rural participants. Waist-to-hip ratio was significantly connected with stress
      at school in rural subjects (p = 0.038) while diastolic blood pressure was
      assicuated with physical inactivity in urban probands (p = 0.04). In both groups,
      systolic blood pressure was related to hypertension while diastolic blood
      pressure correlated with stress at school and hypertension (p = 0.000).
      CONCLUSIONS: The prevalence of key anthropometric risk predictors and unhealthy
      lifestyle in East-Slovakian children and adolescents should lead to targeted
      regional (urban and rural) prophylaxis scheme to reduce the risk of
      atherosclerosis (Tab. 3, Ref. 30).

PMID- 21954526
TI  - Postoperative intrathecal analgesia for primary total hip arthroplasty-
      comparative clinical examination of two different small doses of morphium
      hydrochloride.
AB  - OBJECTIVE: To prospectively compare the spinal analgesia with two different small
      doses of morphium hydrochloride after primary total hip arthroplasty. BACKGROUND:
      In total hip arthroplasty, several techniques for postoperative analgesia can be
      used. In this study, we examined analgesia and side effects of intrathecal
      morphium hydrochloride (MCh) after primary total hip arthroplasty in small doses,
      namely 0.05 mg and 0.1 mg. METHODS: Forty patients were randomized to receive
      either 0.5 ml/0.05 mg, or 0.5 ml/0.1 mg of MCh intrathecally together with 3.5 ml
      of 0.5% isobaric bupivacine hydrochloride. The duration of postoperative
      analgesia, the intensity of the initial pain sensation and the frequency of
      opioid side effects were recorded for the first 24 hours. RESULTS: The mean
      duration of analgesia in group M 0.05 was 14.3 +/- 1.1 hours and was
      significantly shorter than 19.7 +/- 1.7 hours in the M 0.1 group (p < 0.05).
      Visual analogue scale (VAS) score for the initial pain intensity in M 0.05 group
      was 5 (median value). That in M 0.1 group was 3 (median value). The difference
      was not significant (p < 0.05). There was no respiratory depression in the
      groups. The difference in the frequency of nausea and vomiting was not
      significant but that of itching was (p < 0.05). CONCLUSION: Intrathecal usage of
      0.05 mg and 0.1 mg of MCh provides a long-lasting postoperative analgesia. It is
      a practical method to be provided after primary total hip arthroplasty. The
      efficacy of 0.1 mg of MCh is greater compared to that of 0.05 mg of MCh. These
      doses of MCh do not cause respiratory depression but cause nausea, vomiting and
      itching (Tab. 4, Fig. 1, Ref. 11).

PMID- 21954527
TI  - Results of early surgical treatment of intra-articular complex fractures of the
      humerus in adults.
AB  - AIM: We present our results for intra-articular fractures of the elbow which we
      have treated with early restoration of joint combined with the earliest possible
      motion. MATERIALS AND METHODS: Our study group consists of 27 patients and all
      operations were done in Ankara Ataturk Research and Training Hospital 3rd
      Orthopaedic Clinic between February 2004 and December 2008. According to AO
      classification, all of the cases were of type C. Mean age of patients was 24.8
      years (17-32), mean follow-up period was 30 (22-38) months. All patients
      underwent early open reducation, stable osteosynthesis and early rehabilitation.
      RESULTS: Clinical results were evaluated according to the Mayo Elbow Performance
      Scores which were excellent in 20 patients (74%), good in 4 (14.8%), fair in 2
      (7.4%), and bad in 1 patient (3.7%). Postoperative complications including
      infection found in 2 patients (7.4%), minor joint deformity (varus, valgus) in 8
      (29.6%), loss of power (about 1.5 kg) in 14 (51.8%), and medium level heterotypic
      ossification in 2 patients (7.4%). CONCLUSION: We believe that early (first 48
      hours) surgical osteosynthesis with rigid fixation of intra-articular humerus
      fractures combined with postoperative early rehabilitation gives excellent
      results (Fig. 6, Tab. 3, Ref. 18).

PMID- 21954528
TI  - Importance of magnetic resonance imaging in patients with fibrocystic changes.
AB  - INTRODUCTION: A proper detection of atypical epithelial hyperplasia (component of
      FCC) without missing the coexistent malign disease is the main problem in
      evaluating the FCC-affected patients. For some patients, it is not enough to use
      only mammography and ultrasonography in pursuit or decision biopsy. Magnetic
      resonance imaging (MRI) may be important in these patients. Nevertheless, the MRI
      features of FCC are not clearly known because there are very few studies
      specifically focused on FCC. Studies reporting on MRI of breast fibrocystic
      changes are very scarce and their MRI findings are not clearly known. The aim of
      this study was to determine the MRI characteristics of fibrocystic changes.
      METHODS: Twenty-six patients with pathologically proven fibrocystic changes of
      the breast were retrospectively reviewed. The MRI study was performed using 1.5 T
      MR scanner with a phase array bilateral breast coil. The imaging protocol
      consisted of pre-contrast T1-weighted imaging and bilateral dynamic 3D contrast
      enhanced imaging. The morphologic and kinetic features of fibrocystic changes on
      MRI were evaluated. RESULTS: Twenty-four patients showed benign enhancement
      kinetics (type 1), while 2 patients showed malignant enhancement kinetics (type
      2). CONCLUSION: To our knowledge, the analysis of enhancement kinetics may be
      more useful in identifying atypical epithelial hyperplasia and cancer from other
      breast lesions provided that corrections are made for the true phase of menstrual
      cycle (Tab. 1, Fig. 1, Ref. 10).

PMID- 21954529
TI  - Serum thymidine kinase is associated with gastric adenocarcinoma.
AB  - Thymidine kinase (TK) plays an essential role in the processing of thymidine
      within the cell and therefore it is an important marker of proliferation,
      particularly in tumor cells. The aim of our study was to determine the diagnostic
      and prognostic importance of TK measurement in gastric adenocarcinoma. The serum
      level of TK was measured in 72 patients with gastric adenocarcinoma. Serum levels
      of TK were significantly elevated in gastric adenocarcinoma in comparison with
      healthy individuals. Also, we have found that there are significant variations in
      TK serum concentrations when measured that correlate with important variations in
      clinico-pathological features and prognostic significance (Tab. 2, Ref. 16).

PMID- 21954530
TI  - The comparison of the effects of T-piece and CPAP on hemodynamic parameters,
      arterial blood gases and success of weaning.
AB  - Weaning from mechanically ventilation is a period of transition from total
      ventilatory support to spontaneous breathing. The aim of this study was to
      compare the effects of T-Piece and continuous positive airway pressure (CPAP) on
      hemodynamic parameters, arterial blood gases and success of weaning. In a
      prospective, randomized, controlled trial, 40 consecutive patients requiring
      mechanically ventilation in our 8-bed adult general intensive care unit (ICU) for
      >48 hrs were considered eligible for this study. Patients were randomly divided
      into two groups (n: 20). Group T-piece received, 4 L/min, Group CPAP received,
      PEEP < or =5 cm H2O, FiO2 < or = 0.4. At the beginning of the weaning, duration
      of extubation and after 48 hours of extubation the arterial blood samples were
      taken for blood gases analysis, also the mean arterial pressure and heart rate
      were recorded. 40 patients in the ICU were included in the study. There were no
      significant differences within and between T-piece and CPAP groups according to
      hemodynamic parameters and arterial blood gases at the weaning period. The number
      of patients who could be unsuccessful weaned in the T-piece group was higher than
      the number of patients in the group CPAP (p < 0.001, p < 0.01). Whether, the
      technique used to wean patients, in this setting, resulted in a clinically
      relevant improvement in the outcomes addressed above requires further carefully
      designed, randomized, controlled trials (Tab. 4, Ref. 25).

PMID- 21954531
TI  - Body mass index percentile curves for predominantly breastfed children aged 0-2
      years from Ankara, Turkey.
AB  - OBJECTIVE: The percentiles of weight, height and body mass index (BMI) change
      markedly from one country to another and also from one city to another,
      particularly in childhood. The aim of the present study is to construct BMI
      percentile curves for predominantly breastfed Turkish children aged 0-2 years
      from Ankara, Turkey. METHODS: The study population consisted of healthy boys and
      girls aged 0-2 years from the middle-high socioeconomic status between 2002 and
      2004 in well child clinic of Gazi University School of Medicine, Ankara, Turkey.
      The BMI values for boys and girls were calculated from the height and weight
      measurements, and BMI percentile values and curves were obtained separately for
      boys and girls by the LMS method. RESULTS: The current findings indicate that the
      BMI percentile values for boys are higher than those for girls in general. The
      estimated curves for BMI showed that there was a constant increase in BMI values
      towards 7th or 8th month and a slight decrease until 24th month in both boys and
      girls. CONCLUSIONS: The current study presents percentile curves for BMI values
      in predominantly breastfed Turkish children aged 0 to 2 years living in Ankara,
      Turkey. To our knowledge, this is the first study considering BMI percentiles for
      predominantly breastfed Turkish children aged 0-2 years. However, WHO multicenter
      growth reference study curves can be used until constructing multicenter BMI
      reference curves representing Turkey (Fig. 2, Tab. 3, Ref. 19).

PMID- 21954532
TI  - Clinicopathologic characteristics and BRCA-1/BRCA-2 mutations of Turkish patients
      with breast cancer.
AB  - BACKGROUND: BRCA-1 and BRCA-2 are two major susceptibility genes for breast
      cancer. Between 30-70 % of hereditary breast cancers are thought to be attributed
      to mutations in BRCA-1 or BRCA-2. The aim of our study was to investigate the
      clinicopathologic characteristics and BRCA mutations of patients with breast
      cancer living in the northeast region of Turkey. MATERIALS AND METHODS: Two
      hundred eleven patients diagnosed with breast cancer were enrolled in the present
      study. All patients provided their demographic, environmental, family, and
      reproductive traits. Patients were screened for mutations of BRCA-1 and BRCA-2
      with multiple ligation-dependent probe amplification (MLPA) test. RESULTS: In the
      present study, the mean age of breast cancer patients was 50.7 years and the mean
      age at first delivery was 21.8 years. Large genomic rearrangements in BRCA-1 were
      detected in 4 (1.9 %) patients; 2 of them had exon 21 deletions and the remaining
      2 patients had exon 18 and 19 deletions. No BRCA-2 rearrangements were detected
      in the study population. CONCLUSIONS: Different mutation analyses results were
      detected in different countries by using different testing techniques. The
      characteristics and sensitivities of patients as determined by all methods were
      different in these studies. Due to these factors, BRCA mutation rates were
      different. This is the first study where MLPA was used to screen BRCA-1 and BRCA
      2 mutations in Turkish population (Tab. 1, Ref. 10).

PMID- 21954533
TI  - Our experience with McKusick-Kaufman syndrome patients.
AB  - AIM: McKusick-Kaufman syndrome (MKKS) is a rare autosomal recessive disorder.
      Less than one hundred cases have been reported in the English literature to date.
      We report three different aged children with a large hydrometrocolpos and
      postaxial polydactyl. PATIENTS AND RESULTS: These children had various degrees of
      associated renal disorders. Bardet Biedl syndrome (BBS) is characterized by
      retinal dystrophy or retinitis pigmentosa, postaxial polydactyl, obesity,
      nephropathy, mental disturbances or mental retardation. Typically MKKS is
      diagnosed in young children especially in neonates whereas the diagnosis of BBS
      is delayed until the teenage years. CONCLUSION: All MKKS cases should be re
      evaluated for Retinitis pigmentosa, other signs of BBS and for disorders that may
      worsen with time (Ref. 12).

PMID- 21954534
TI  - A memantin HCL intoxication responsive to plasmapheresis therapy.
AB  - Memantin HCL (Ebixa) is a drug which antagonizes the effects of N-methyl-D
      aspartat receptors and which is used for the treatment of acute Alzheimer
      patients. Plasmapheresis is a method of cleaning nonspecific extracorporeal blood
      and it is applied in many immunologic and toxicologic diseases. Female patient at
      the age of 35 was admitted to the emergency department with complaints of
      tendency to sleep and sensory loss. About 12 hours before her history she had
      taken 200 tablets of 10 mg memantin HCL (Ebixa) (2000 mg) and she was transferred
      to an intensive care department with the diagnosis of drug toxicity (400 mg toxic
      dose). Her memantin HCL (Ebixa) level in blood was 12,000 ng/mL. It was reported
      in her physical examination that she was unconscious, her general condition was
      bad, there were no cooperation and orientation, ahe hadmydriasis and reflexes of
      light, cornea and eyelash were bilaterally positive and she had horizontal
      nystagmus. Glascow Coma Scale of the patient was 6, body temperature was 37.5
      degrees C and she had tachycardia (130/min) and hypertension (160/90 mmHg).
      Intravenous Diazepam was effective aginst recurring convulsions. Sinusoidal
      tachycardia was detected with electrocardiography (EKG) and respiratory alkalosis
      in arterial blood gases. Six cysles of plasmapheresis were aplied and in the
      sixth cycle the memantin HCL (Ebixa) level turned to normal. As a result of the
      sixth plasmapheresis the findings were normal and that is why she was discharged
      from the hospital. Plasmapheresis should be taken into consideration in case of
      drug overdose or high doses of plasmatic proteinous drug toxicities (Ref. 11).

PMID- 21954535
TI  - Urethral stricture in adult as a consequence of childhood hypospadias repair.
AB  - We report our experience in treating such patients. A retrospective chart review
      was performed from 2004 through 2007 in Urology Department of Dhaka Medical
      College Hospital by using the convenient type of purposive sampling. In cases
      undergoing perineal urethrostomy, we suggested the "side-to-side" technique,
      which comprised longitudinal urethrotomy and everting the mucosal and submucosal
      layers of the urethra to the incised skin. Graft-based urethroplasty using buccal
      mucosal graft, in one-stage or two-stage repairs, was the preferred choice of
      formal reconstruction. Patients undergoing hypospadias surgery should receive
      lifelong follow-up protocol to detect latent urethral strictures (Fig. 8, Ref.
      12).

PMID- 21954536
TI  - Biochemical insight into soman intoxication and treatment with atropine, HI-6,
      trimedoxime, and K203 in a rat model.
AB  - OBJECTIVE: The present experiment is based on biochemical assessment of nerve
      agent soman intoxication and atropine, respectively atropine and HI-6,
      trimedoxime or K203 treatment in rats. BACKGROUND: Nerve agents are toxic
      substances irreversibly inhibiting enzyme acetylcholinesterase (AChE). Treatment
      is typically based on application of atropine and oxime reactivator. Atropine is
      able to protect overstimulation of muscarinic acetylcholine receptors.
      Application of oxime reactivator enable return of AChE activity and full
      suppression of intoxication. METHODS: In a total, fifteen biochemical markers
      were assayed in plasma or blood of intoxicated animals. 42 rats were divided into
      7 groups each 6 individuals. The first group was exposed to atropine; the second
      group was exposed to one LD50 of soman and atropine. The groups 3-5 were exposed
      in a same way as the second group and were treated with oxime reactivators: HI-6
      (group 3), trimedoxime (4) and K203 (5). The sixth group was control treated with
      saline solution only. The last (seventh) group was intoxicated with soman only.
      RESULTS: The most striking shifts were found for blood acetylcholinesterase and
      plasma creatinine, glucose, inorganic phosphate as well as uric acid. Lactate
      dehydrogenase and aspartate aminotransferase assays were useless due to soman
      interference. CONCLUSION: It was demonstrated that treatment was able to protect
      poisoned animals from metabolic disorder represented by hyperglycemia and
      nephropathy represented by hyperuricemia and elevated creatinine. Soman exposure
      and treatment with the oxime reactivators and/or atropine contains quite complex
      and still not well understood side mechanisms (Tab. 2, Fig. 1, Ref. 25).

PMID- 21954537
TI  - Diosmin ameliorates intestinal injury induced by hepatic ischemia reperfusion in
      rats.
AB  - BACKGROUND: Hepatic ischemia-reperfusion causes histologic injury to the
      intestinal mucosa. We investigated the effects of diosmin, a phelobotrophic drug
      with antioxidant and antiinflammatory effects, on intestinal injury in the
      experimental liver ischemia-reperfusion model. MATERIALS AND METHODS: Fourty rats
      were divided into four groups: sham group (Group 1), control group (Group 2),
      perop diosmin group (50 mg/kg) treatment group (Group 3) and preop 10-day diosmin
      (50 mg/kg) treatment group (Group 4). Ischemia-reperfusion model was carried out
      by clamping the hepatic pedicle for 60 min and then reperfusing the liver for 90
      min. At the end of procedures, blood and ileum tissue samples were obtained for
      biochemical and histopathological assessments. RESULTS: According to the results
      of liver function tests (AST, ALT and LDH) there was a significant difference
      between the control and other groups (p < 0.001 for all). According to the plasma
      and ileum oxidative stress parameters (MDA, GSH-Px and XO), there was a
      significant difference between the control and other groups (p < 0.05 for all).
      Histopathologically; the specimens in Group 2 showed specific morphological
      abnormalities (the epithelial lining of the apical surface of villi was
      degenerated and desquamated to the lumen). Group 3 and 4 showed ileal
      histomorphology similar to the sham group. Pathological scores were significantly
      different between Group 2 and other groups. CONCLUSIONS: Diosmin can be
      administered for protection from destructive effects of hepatic ischemia
      reperfusion injury on intestine in both emergent and elective hepatic surgical
      operations in which the possible ischemic periods are expected (Tab. 4, Fig. 1,
      Ref. 39).

PMID- 21954538
TI  - Serum des-gamma-carboxyprothrombin in patients with pancreatic head
      adenocarcinoma.
AB  - The total des-gamma-carboxyprothrombin (DCP) produced in pancreatic
      adenocarcinoma and the correlation between the tissue DCP and serum DCP levels
      has been examined. Fifty patients with resectable pancreatic head cancer were
      examined regarding both the tissue and serum levels of DCP. The mean tissue DCP
      in the cancer tissue, non-cancer tissue, the serum levels in patients, and the
      serum levels in controls was 190.500 mAU/ml mg protein, 32.000 mAU/ml mg protein,
      and 46.000 mAU, and 10.000 mAU, respectively. The elevation of tissue and serum
      levels of DCP in pancreatic adenocarcinoma patients is a very useful marker for
      pancreatic adnocarcinoma and should be used without any other tumor marker (Tab.
      2, Ref. 15).

PMID- 21954539
TI  - Can the patient-reported outcome instruments determine disease activity in
      rheumatoid arthritis?
AB  - OBJECTIVES: The aim of this study was to investigate the indicative value of the
      patient-reported outcome instruments (PROs) on disease activity in rheumatoid
      arthritis (RA). METHODS: Three hundred sixty eight patients with RA were included
      in this cross-sectional study. Disease activity was evaluated using both the
      Disease Activity Score 28 (DAS 28) and the Clinical Disease Activity Index
      (CDAI). Patients who had DAS 28 score < 3.60 points and CDAI score <10.00 points
      were allocated into the "low disease activity" group and those who had DAS 28
      score > or = 3.60 points and CDAI score > or = 10.00 points into the "moderate or
      high disease activity" group. The Health Assessment Questionnaire (HAQ),
      Nottingham Health Profile (NHP), Rheumatoid Arthritis Quality of Life (RAQoL),
      and Short Form 36 (SF 36) were used as PROs. Logistic regression analysis was
      used to find variables, which had an indicative value for disease activity.
      RESULTS: HAQ, pain and emotional reaction subscales of NHP, and bodily pain,
      general health and social functioning subscales of SF 36 had independent
      indicative values, when DAS 28 was used as dependent variable. On the other hand,
      HAQ, pain and emotional reaction subscales of NHP, and general health and
      emotional role limitation subscales of SF 36 had indicative values when CDAI was
      used as dependent variable. DAS 28 and CDAI both showed HAQ as the parameter with
      the highest odds ratio (OR). But RAQoL had shown no independent indicative value
      for projecting disease activity. CONCLUSION: It was concluded that HAQ could
      determine disease activity in RA better than other PROs included in this study
      (Tab. 4, Ref. 36).

PMID- 21954540
TI  - Elevated pulse pressure in treated hypertensive patients during 24-hour
      ambulatory blood pressure monitoring.
AB  - OBJECTIVES: We tested whether antihypertensive therapy may alter PP independently
      from other blood pressure parameters. METHODS: Data from 24-hour ambulatory blood
      pressure monitoring (24-h ABPM) were compared between healthy normotensive
      controls and hypertensive subjects successfully treated (sBP/dBP 24-hour average
      bellow 130/80 mmHg) with antihypertensive medication either with absence
      (Treated) or presence of additional risk factors (Treated + R). These groups were
      compared with poorly treated hypertensives (sBP/dBP over 130/80 mmHg) with
      absence (Uncontrolled) or presence of additional risk factors (Uncontrolled + R).
      We studied mean 24-hour systolic and diastolic blood pressure (sBP and dBP), mean
      arterial pressure (MAP) and pulse pressure (PP). RESULTS: In Treated and Treated
      + R groups, sBP and dBP were appropriately controlled by antihypertensive
      medication, however PP was significantly increased in both groups (49 +/- 1 mmHg
      and 51 +/- 2 mmHg, resp., in both p < 0.05) as compared to the controls (43 +/- 1
      mmHg). In Uncontrolled and Uncontrolled + R groups, values of PP were even
      significantly higher (60 +/- 2 mmHg and 76 +/- 3, resp.) as compared to controls
      as well as to successfully treated groups (p < 0.05). PP was significantly
      positively correlated to sBP in all groups (p < 0.05), except Treated + R. Other
      parameters (age, body mass index, MAP) showed overall significant positive
      relationship only in pooled hypertensive population. CONCLUSION: 24-h ABPM
      revealed significantly increased PP, in spite of proper control of sBP and dBP in
      treated hypertensive patients. We propose that 24-h PP could provide additional
      information in the evaluation of antihypertensive therapy, even when depending on
      sBP (Tab. 3, Fig. 2, Ref. 39).

PMID- 21954541
TI  - Aminotransferase activity as a poor predictor of liver disease progression in
      dialysis patients with chronic hepatitis C.
AB  - Lower aminotransferase activity in dialysis patients makes the assessment of the
      natural history of hepatitis C virus (HCV) infection difficult. The aim of the
      study was to determine the risk factors associated with the aminotransferase
      activity in dialysis patients with chronic hepatitis C. According to the serum
      levels of alanine aminotransferase (ALT) during the follow-up, the patients were
      divided in the two groups. The first group consisted of 34 chronically HCV
      infected patients with persistently normal levels of ALT. The second group
      included 46 chronically HCV infected patients with elevated levels of ALT.
      Genotype 1 was the dominant genotype in both groups (78 patients, 97.5%).
      Patients with the elevated ALT levels were characterized with a significantly
      shorter dialysis duration (p = 0.048) and a significantly shorter duration of HCV
      infection (p = 0.005) compared to the patients with persistently normal levels of
      ALT. The values of measured ultrasound parameters were not significantly
      different between the two groups. The univariate analysis identified a higher
      serum level of direct bilirubin (p = 0.044), shorter duration of dialysis
      (p=0.048), and shorter duration of HCV infection (p = 0.005) as potential
      predictors of elevated serum ALT levels in dialysis patients. After a stepwise
      logistic regression, none of the potential predictors was independently
      associated with the elevated ALT levels. Serum aminotransferase levels are poor
      predictors of liver disease progression in dialysis patients with chronic
      hepatitis C. Further studies should be conducted in order to identify non
      invasive indicators of the disease progression in uremic patients with hepatitis
      C (Tab. 3, Ref. 22).

PMID- 21954542
TI  - One day surgery for pilonidal disease.
AB  - BACKGROUND: There are numerous surgical options for pilonidal disease. We
      practice "D" excision technique with a suction drain under local anesthesia as a
      1 day surgery procedure. METHODS: 54 patients had pilonidal surgery between March
      2001 and December 2003. "D" excision with a suction drain under local anesthesia
      was performed. An attention was given not to make a wide excision. Tracks lying
      outside the excised area were removed by the same technique with small "D"
      incisions. Subcutaneous tissues were sutured with absorbable interrupted sutures
      in layers. The wound was closed subcutaneously with running monofilament non
      absorbable suture. All the operations were performed as 1 day surgery procedure.
      33 of 54 patients had been reached by call on March 2009. RESULTS: Recurrence was
      seen in four of 54 patients (7.4%). Follow-up of two of these four patients have
      been uneventful after the second operation. Infection developed in two patients
      (3.7%) and caused a wound dehiscence. Both patients healed without any problems.
      All of the patients were able to return to their daily activities on the 3-5
      postoperative day. CONCLUSION: "D" excision technique as a 1 day surgery
      procedure for pilonidal disease is performed with a low complication and
      recurrence rate (Ref. 19).

PMID- 21954543
TI  - Postoperative changes related to intraoperative blood transfusions.
AB  - OBJECTIVE: Wound infection, flap necrosis rates and peripheral complete blood
      cell count changes related to intraoperative whole-blood transfusions were
      investigated. BACKGROUND: Evidence is growing that whole-blood cell transfusions
      are immunosuppressive and predispose patients to postoperative infections.
      METHODS: 102 female breast carcinoma patients with hemoglobin levels = 10 g/dl
      before modified radical mastectomy and < 10 g/dl intraoperatively but with no
      signs of oxygen debt were included. Group I included patients who had received
      two units of whole-blood transfusions intraoperatively. Patients who had received
      no transfusion were in group II. Peripheral complete blood cell count, wound
      infection rates and flap necrosis were compared. RESULTS: Perioperative
      neutrophile and monocyte count increased in both groups. This increase was
      especially significant in the transfused group (p < 0.05). In both groups, these
      changes returned to normal levels on the tenth postoperative day. The decreased
      perioperative basophile count did not return to the baseline even on the tenth
      postoperative day in group I (p < 0.05). Lymphocyte count, and flap necrosis did
      not differ between the groups (p > 0.05). Wound infection seemed to take place
      and increase in the transfused group (p < 0.05). CONCLUSION: Two units of whole
      blood transfusions seem to increase wound infection and decrease basophile count
      in this series (Tab. 3, Ref. 30).

PMID- 21954544
TI  - Follow-up after primary therapy of malignant epithelial ovarian tumors.
AB  - Follow-up after finishing the primary therapy has become a routine aimed to an
      early detection of relapse, decreasing the mortality and improving the quality of
      patient's life. Main aim of the follow-up is to prolong the life of the patient.
      No prospective randomized study confirming the scientific character of such aims
      has been published, so far. Opinions on benefit from the follow-up are
      conflicting. It is supposed, that early relapse detection can contribute to
      prolonged survival and on the other hand, there are opinions, that regular
      medical examinations can postpone relapse detection in symptomatic patients.
      Patients after treatment of an early stage should be followed up in regular
      intervals according to the presented scheme. Patients in advanced stages of the
      disease should be treated in a principally different way, based on free access to
      post primary treatment care. Quality of life has to be emphasized. The main
      purpose of the follow-up is to detect relapse during the time, when it is
      curable. When this condition has been fulfilled, the follow- up can have medical
      and economic relevance. Optimal screening is based on results from prospective
      randomized studies which objectively compare different models of the follow-up.
      Routine intensive follow-up might not be cost-effective and might substantially
      raise patient's anxiety at the same time. Patient education regarding early
      symptoms of relapse and free access could represent a cost-effective model. In
      order to decide between minimal and intensive follow-up, needs of all three
      participating members: patients, doctors and healthcare system have to be taken
      into account (Tab. 1, Ref. 105).

PMID- 21954545
TI  - Malignant thymoma as etiology of bilateral, biventricular cardiac failure.
AB  - The authors report on a case of a 60-year-old female admitted to hospital with
      symptoms of bilateral cardiac failure. Upon ultrasonic examination of the heart,
      a massive pericardial exudate was diagnosed. Pericardial drainage was done to
      find the cause of pericardial effusion. Cells of malignant lymphoma were detected
      cytologically while immunophenotypization demonstrated a malignant lymphoma
      exudate. A computed tomography (CT) examination of the thorax disclosed a
      mediastinal tumour with infiltration of both lungs, vascular structures and
      dissemination on the chest wall. A CT-guided tumour biopsy was performed to
      confirm or exclude a lymphoproliferative process. Histopathologically, an
      invasive cortical thymoma was verified. The tumour was evaluated as stage III
      thymoma according to Masaoka. This case report highlights a rare malignant
      thymoma, its clinical symptoms, diagnosis, therapy and prognosis (Fig. 2, Ref.
      10).

PMID- 21954546
TI  - Bilateral breast cancer: a male patient.
AB  - Bilateral breast cancer represents less than 2% of male patients with breast
      cancer. A 63-year old male presented with a mass at right breast and modified
      radical mastectomy was performed. Pathology was reported as invasive ductal
      carcinoma. Radiotherapy and tamoxifen was administered following chemotherapy. At
      the 5th month, a mass was detected at left breast and modified radical mastectomy
      was performed. Chemotherapy was started postoperatively. BRCA1 and BRCA2 were
      reported negative. Although male breast cancer is rare, male patients with breast
      cancer may have cancer at the other breast (Fig. 1, Ref. 5).

PMID- 21954548
TI  - The intensity of antibiotic usage in the university hospital and the
      investigation of an inappropriate use of antibiotics.
AB  - AIMS: In the present study, we intended to investigate the intensity of
      antibiotic administration in our hospital and the ratio of an inappropriate
      antibiotic usage. MATERIAL AND METHOD: Related data was collected during 3
      consecutive days between 1-3 July 2009 at the Mustafa Kemal University, Faculty
      of Medicine Hospital. The antimicrobial usage was calculated as defined daily
      doses (DDDs) per 100 bed-days (BD) according to 2009 ATC-DDD index. RESULTS:
      Antibiotics were administered to 74 patients (61.5%) out of 121 who were
      hospitalized in our hospital. Antibiotic usage in the internal clinics was
      intended for therapeutical reasons in 18 patients (94.7%) and for prophylactic
      reasons in 35 patients (77.8%) in the surgical clinics. The use of antibiotics in
      44 patients (59.7%) out of 74 was appropriate. However, an inappropriate
      antibiotic use was detected in 30 patients (40.5%). The inappropriate antibiotics
      were administered to 21 patients (70%) who were hospitalized in the surgical
      clinics. A three days total antimicrobial consumption index value in the hospital
      was 81,19 DDD/100 BD, while this value was found 25,45 DDD/100 BD for the
      internal clinics and 38,39 DDD/100 BD for the surgical clinics. A positive
      correlation was observed among the inappropriate antibiotic usage and the
      antibiotic consumption (p<0.001). DISCUSSION: Consequently, the ratio of an
      inappropriate antibiotic usage in our hospital is high and parallel to this, the
      antibiotic consumption ratio is excessive. It is necessary to share
      microbiological data and provide an adequate education to reduce the antibiotic
      consumption and enable a better and rational antibiotic consumption (Tab. 2, Fig.
      2, Ref. 22).

PMID- 21954547
TI  - Class II alleles HLA-DQB1* 0301 among a seven-membered Egyptian family of a child
      with oral pemphigoid.
AB  - OBJECTIVES: The presence of HLA-DBQ1* 0301 allele in an Egyptian patient with
      oral pemphigoid and six of his family members was investigated. BACKGROUND: Oral
      pemphigoid is a variant of vesiculobullous mucous membrane pemphigoid with an
      immunogenetic predisposition related to defects in major histocompatibility
      complex (OMIM 604305), HLA-DQB 1 alleles. METHODS: High resolution typing of HLA
      DQB 1*0301 allele was carried out for the seven members of an Egyptian family
      including the child affected with oral pemphigoid. RESULTS: Both parents and
      three children including the proband were found to be carriers for the studied
      allele, while the other two children were not. CONCLUSION: Participation of HLA
      DBQ1*0301 allele was not informative for both susceptibility and/or phenotypic
      expression of the disease within the studied family (Fig. 2, Ref. 31).

PMID- 21954549
TI  - [Effects of phytohormones on hairy root growth and tanshinone biosynthesis of
      Salvia miltiorrhiza].
AB  - OBJECTIVE: To study the effects of different phytohormones on the growth of hairy
      root and biosynthesis of tanshinone II A in Salvia miltiorrhiza. METHODS: Salvia
      miltiorrhiza hairy root was induced by organizational culture method. Tanshinone
      was extracted with ultrasonic method and detected by high performance liquid
      chromatography (HPLC). RESULTS: The phytohormone combination of GA3 and 6-BA at
      different concentrations adding to 1/2 MS medium had obviously inhibitory effect
      on the hairy root growth of Salvia miltiorrhiza. And the highest inhibition rate
      was up to 100% (hairy roots were death). However, the growth of hairy roots could
      be obviously promoted by the combination of KT (1.0 mg/L) and IBA (1.0 mg/L),
      increasing 3. 251 times than that of the control. Total tanshinone II A content
      in hairy roots bodies was the highest under the combination of 0.2 mg/L NAA and
      3.0 mg/L 6-BA. 6-BA of 2.0 mg/L played a significant role in promoting tanshinone
      II A biosynthesis, and the tanshinone II A concentration was 3.012 times higher
      than that of the control. CONCLUSION: Different phytohormones and its combination
      adding to 1/2 MS medium has significant influence on the hairy root growth and
      the content of tanshinone II A in Salvia miltiorrhiza.

PMID- 21954550
TI  - [Effect of exogenous nitric oxide donor SNP on seed germination and antioxidase
      activities of Perilla frutescens seedlings under NaCl stress].
AB  - OBJECTIVE: To explore the method of improving the salt resistance ability of
      seeds and seedlings of Perilla frutescens under NaCl stress. METHODS:
      Physiological indexes of Perilla frutescens seeds treated by sodium nitroprusside
      (SNP) under NaCl stress like the germination vigor, germination rate, germination
      index and vigor index were measured. And other indexes like the activities of
      nitrate reductase (NR), malondialdehyde (MDA), superoxide (SOD), peroxidase (POD)
      and catalase (CAT) were also measured. RESULTS: The germination indexes of
      Perilla frutescens seeds under NaCl stress had obvious inhibition. But after the
      treatment with different concentrations of SNP, every germination indexes were
      all increased. And the seeds that treated with SNP with the concentration of 0.1
      mmol/L has the most significantly increase in every index. The germination vigor
      was 60.4%, the germination rate was 78.3%, the germination index and vigor index
      were 13.7 and 0.1093 respectively. The content of MDA was decreased after the
      treatment of SNP. The activities of four enzymes included NR, SOD, POD and CAT
      were increased with the treatment of SNP, and get the maximin (1.52 microg/g x h,
      0.32 U/mg, 5.9 U/mg and 4.8 U/mg respectively) with the concentration of 0.1
      mmol/L SNP. CONCLUSION: SNP with concentration of 0.1 mmol/L could significantly
      alleviate the damages to the seeds and seedlings of Perilla frutescens under NaCl
      stress, and promote the salt resistance of the seeds and seedlings.

PMID- 21954551
TI  - [Effect of Eupolyphaga fibrinolytic protein on microvessel density and the
      expression of vascular endothelial growth factor in mice tumor].
AB  - OBJECTIVE: To study the effect of Eupolyphaga fibrinolyric protein (EFP) on
      microvessel density (MVD) and the expression of vascular endthelial growth factor
      in transplantation S180 and H22 mice. METHODS: The MVD in tumor was measured with
      immunohistochemical SP method and the VEGF level in serum was measured with ELISA
      method. RESULTS: Compared with the control group, EFP could significantly reduce
      the microvessel density and decrease the expression of vascular endothelial
      growth factor. CONCLUSION: EFP has the effect of anti-angiogenesis.

PMID- 21954552
TI  - [Determination of geniposide, crocin and crocetin in different processing
      products of fructus gardeniae by HPLC-ELSD].
AB  - OBJECTIVE: To develop a HPLC- ELSD method for determination the contents of
      geniposide, crocin and crocetin in different processing products of Fructus
      Gardeniae. METHODS: The separation was performed in the HyperClone ODS C18 column
      (250 mm x 4. 6 mm, 5 microm) with linear gradient elution using methanol-water
      and 0.05% phosphoric acid in water, the flowing rate was 0.8 mL/min, the column
      temperature was 30 degrees C, and the ELSD parameter was as follow: 70 degrees C
      as atomization temperature and 2.0 L/min as the gas flowing rate. RESULTS: The
      contents of geniposide and crocin in raw, yellowish, carbocoal and scorched
      Fructus Gardeniae decreased with the deepening of processing degree. However, the
      content of crocetin in carbocoal and scorched Fructus Gardeniae increased
      comparing with the raw one. CONCLUSION: This is a simple and credible quality
      control method, and can be used for the quality control and comprehensive
      evaluation for different processed products of Fructus Gardeniae.

PMID- 21954553
TI  - [Studies on the chemical constituents of the herb of Antenoron filiforme].
AB  - OBJECTIVE: To study the chemical constituents of the herb of Antenoron filiforme.
      METHODS: The constituents were separated by column chromatography and their
      structures were elucidated by spectral data analyses. RESULTS: Eleven compounds
      were isolated from the ethanol extract of A. filiforme and identified as, bronane
      5-hydroxy-2-O-beta-D-glucopyranoside (I), adenosine (II), bonaroside (III),
      rhamnetin (IV), hyperoside (V), rhamnetin-3-O-beta-D-galactopyranoside (VI),
      kaempferol-3, 7-O-bis-alpha-L-rhamnopyranoside (VII), stigmasterol (VIII),
      nonacosanoic acid (IX), daucosterol (X), 3beta-sitosterol (XI). CONCLUSION: All
      compounds are obtained from A. filiforme for the first time.

PMID- 21954554
TI  - [The study of the secondary metabolites from fungus Paecilomyces sp].
AB  - OBJECTIVE: To get active secondary metabolites from the fungus Paecilomyces sp..
      METHODS: The strain Paecilomyces sp. was further grown in solid-substrate
      fermentation cultures, the metabolites were got by application of different
      separation techniques, such as silica gel, Sephadex LH-20 column chromatography,
      and reversed-phase high performance liquid chromatography. Their structures were
      identified by comprehensive spectroscopic methods. RESULTS: Four compounds were
      isolated and identified as Cerebroside C (1), Cerebroside D (2), 2-Hydroxybenzyl
      alcohol (3), 2-(4-Hydroxyphenyl) ethanol. CONCLUSION: Four compounds are isolated
      from Paecilomyces sp. for the first time.

PMID- 21954555
TI  - [Isolation and identification of brominated alkaloids from the sponge Ircinia
      sp].
AB  - OBJECTIVE: To study the alkaloids from sponge Ircinia sp.. METHODS: The alkaloids
      were isolated and purified by various chromatographic techniques, and their
      structures were elucidated by physicochemical and spectral data. RESULTS: Five
      alkaloids were isolated and identified as fistularin-1 (1), fistularin-3 (2),
      aerothionin (3), 11 -hydroxyaerothionin (4), suberamolline A (5). CONCLUSION: All
      the alkaloids are isolated from Ircinia sp. for the first time.

PMID- 21954556
TI  - [Studies on the flavonoids from the flowers of Hylocereus undatus].
AB  - OBJECTIVE: To study the chemical constituents of the flowers of Hylocereus
      undatus. METHODS: The constituents were isolated and purified by various modern
      chromatographic techniques. The structures of the compounds were elucidated based
      on their physicochemical properties and spectral analyses. RESULTS: Thirteen
      compounds were isolated from the flowers of H. undatus. Their structures were
      elucidated as kaempferol (1), quercetin (2), isorhamnetin (3), kaempferol 3-O
      alpha-L-arabinfuranoside (4), kaempferol 3-O-beta-D-glucopyranoside (5),
      quercetin 3-O-beta-D-glucopyranoside (6), isorhamnetin 3-O-beta-D-glucopyranoside
      (7), kaempferol 3-O-beta-D-galactopyranoside (8), quercetin 3-O-beta-D
      galactopyranoside (9), kaempferol 3-O-beta-D-rutinoside (10), isorhamnetin 3-O
      beta-D-rutinoside (11), kaempferol 3-O-alpha-L-rhamopyranosyl-(1 --> 6)-beta-D
      galactopyranoside (12), and isorhamnetin 3-O-alpha-L-rhamopyranosyl-(1 --> 6)
      beta-D-galactopyranoside (13). CONCLUSION: All the compounds are isolated from
      this plant for the first time.

PMID- 21954557
TI  - [Studies on the chemical constituents from the roots of Kalopanax septemlobus].
AB  - OBJECTIVE: To investigate the chemical constituents of Kalopanax septemlobus.
      METHODS: Chromatographic techniques including silica gel, gel, semi-preparative
      HPLC and PTLC as well as recrystallization were employed in the isolation and
      purification, and the structures were elucidated by spectral analysis and
      physical and chemical properties. RESULTS: 6 compounds were identified as
      liriodendrin (1), (-) -syringarenol (2), trans-coniferyl aldehyde (3), trans
      caffeic acid (4), beta-daucosterol (5), beta-sitosterol (6). CONCLUSION:
      Compounds 2 -5 are obtained from this genus for the first time.

PMID- 21954558
TI  - [Studies on the chemical constituents from Conyza canadensis].
AB  - OBJECTIVE: To study the chemical constituents of Conyza canadensis. METHODS:
      Chromatographic methods including HP20 macroporous resin, silica gel, Sephadex LH
      20 and eighteen alkyl silane bonding silica gel (ODS) were used for the isolation
      and purification of Conyza canadensis. The structures of the obtained compounds
      were identified by physical chemistry and spectroscopic data. RESULTS: Six
      compounds were isolated from ethanol-extraction of water area of C. canadensis
      and identified as Eugenyl beta-Psd (1), scutellarin (2), luteolin-7-O-beta-D
      glucuronide (3), quercetin (4), quercetin-3-O-beta-D-glucopyranoside (5) and
      luteolin (6). CONCLUSION: Compounds 1,3,5 and 6 are isolated from C. canadensis
      for the first time.

PMID- 21954559
TI  - [Studies on the chemical constituents from the flowers of Ophiopogon japonicus].
AB  - OBJECTIVE: To study the chemical constituents from the flowers of Ophiopogon
      japonicus. METHODS: Column chromatography and spectral analysis were used to
      isolate and identify the constituents. RESULTS: Eleven compounds were obtained
      and identified as beta-sitosterol (I), diosgenin (II), daucosterol (III),
      ophiopogonin C' (IV), dioscin (V), 7-dihy-droxy-6-methyl-3-(4'-hydroxybenzyl)
      chroman-4-one(VI), luteolin (VII), kaempferol-3-O-beta-D-glucopyranosides (VIII),
      kaempferol-3-O-(6"-tigloyl) -beta-D-glucopyranosides (IX), kaempferol-3-O-(6"
      acetyl) -beta-D-glucopyranosides (X), glucose (XI). CONCLUSION: Eleven compounds
      are obtained from the flowers of O. japonicus for the first time. Compond VI is
      isolated as a simple substance compound of O. japonicus for the first time.
      Componds VII, VIII, IX and X are isolated from this genus for the first time.

PMID- 21954560
TI  - [Studies on the alkaloids of Senecio scandens growing in Guangdong].
AB  - OBJECTIVE: To study alkaloids of Senecio scandens growing in Guangdong. METHODS:
      The rapid resolution liquid chromatography-electrospray ionization mass
      spectrometry (RRLC-ESI-MS/MS) was used to analyse alkaloids of Senecio scandens
      growing in Guangdong, and senkirkine was isolated and purified by silica gel
      column chromatography. RESULTS: Four alkaloids were identified as senkirkine,
      dehydrosenkirkine, monocrotaline and adonifoline, and senkirkine was firstly
      isolated from Senecio scandens growing in Guangdong. CONCLUSION: Senkirkine is
      the main component of Senecio scandens growing in Guangdong.

PMID- 21954561
TI  - [Study on four natures of six flavor Chinese materia medica as rhizoma coptidis
      and radix aconiti lateralis praeparata etc].
AB  - OBJECTIVE: To study on four natures of six flavor Chinese meteria medica as
      rhizoma coptidis, radix scutellariae, radix aconiti lateralis praeparata, rhizoma
      zingiberis, rhizoma dioscoreae and radix et rhizoma glycyrrhizae. METHODS: To
      determine the biological enthalpy of extracts of Chinese meteria medica, rats'
      metabolites and excrement after feeding the extract of medicines and the standard
      substance of basic by the oxygen bomb calorimeter. RESULTS: The biological
      enthalpy of rhizoma coptidis, radix scutellariae, radix aconiti lateralis
      praeparata, rhizoma zingiberis, rhizoma dioscoreae and radix et rhizoma
      glycyrrhizae were (3006.02 +/- 201.51)J/g, (1592.41 +/- 404.41)J/g, -(433.10 +/-
      64.43)J/g, -(665.72 +/- 198.59)J/g, -(18.41 +/- 50.08)J/g, (29.55 +/- 55.13)J/g
      respectively. According to the results, rhizoma coptidis and radix scutellariae
      showed cold properties, whereas those of radix aconiti lateralis praeparata and
      rhizoma zingiberis were opposite as well as rhizoma dioscoreae and radix et
      rhizoma glycyrrhizae were neutral drugs. CONCLUSION: The four natures of Chinese
      meteria medica presente in traditional Chinese pharmacology could be determined
      by the mathematical model of four natures.

PMID- 21954562
TI  - Studies on cell migration model in intestinal epithelial restitution for
      pharmacological research.
AB  - OBJECTIVE: To set up a suitable IEC-6 migration model for pharmacological
      research and observe the effect of complex polysaccharide from Astragalus
      membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao to IEC-6 cell migration.
      METHODS: The main conditions related to the establishment of the model, including
      the planting density of the cell, the observation time after scratching, the
      concentration of the auxiliary material Matrigel, the treatment of the serum
      starvation, the concentration of alpha-difluoromethylornithine (DFMO), an
      inhibitor of the cell migration, were investigated respectively; and the effects
      of the tested medicines on the model were observed. RESULTS: 4 x 10(5) cell/mL
      was the suitable planting density of the cell in the 6-well plate; at the 24th
      hour after scratching was the appropriate time to count the migrating cells; and
      the proper concentration of Matrigel was 5%; the serum-starvation could evidently
      reduce the migrating cells, so the culture medium should contain the serum; 2.5 -
      5 mmol/L DFMO was proper for inhibition of the cell migration. Complex
      polysaccharide from Astragalus membranaceus and spermidine both can promote cell
      migration. CONCLUSION: The established model of IEC-6 cell migration was suitable
      for intestinal epithelial restitution such as the researches on
      pathophysiological mechanisms is the effects of the medicines on the cell
      migration.

PMID- 21954563
TI  - [Effects and mechanisms of osthole on sciatica induced by lumber disc
      herniation].
AB  - OBJECTIVE: To study the effects of osthole on sciatica induced by lumber disc
      herniation and its mechanisms. METHODS: 54 male SD rats were randomly divided
      into 6 groups. Model (M) group (n = 12): Autologous nucleus pulposus was
      harvested from the tail and applied to the L5 dorsal root ganglion (DRG) and
      epidural space. Epidural catheterization was performed. Control(C) group (n =
      12): On the basis of nucleus pulposus group, 50 microL tween-80 was administered
      epidurally on the day 6th after surgery. T2 (n = 6), T6 (n = 12), T13 (n = 6) and
      T20 (n = 6) group: 50 microL 2% osthole was administered epidurally on the 2th,
      6th, 13th day and 20th after surgery respectively. General behaviors were
      observed and 50% paw withdrawal threshold (50% PWT) was measured 1 day before
      surgery, on the 1st, 3th, 7th,14th, 21th, 28th day after surgery, immediately
      before and 1 hour after osthole or tween-80 administration in each group. On the
      7th day after surgery, the left L5 DRGs were obtained for detecting the
      expression of NOS and COX-2 in M, C and T6 group with 6 rats. RESULTS: No
      lameness or autophagy was oberserved. 50% PWT decreased after surgery (P < 0.05).
      In T2 and T6 group, 50% PWT after osthole administration were significantly
      higher than those of M group and C group (P < 0.05), which recovered to the same
      level as 1 day before surgery (P > 0.05). In T13 and T20 group, 50% PWT 1 hour
      after osthole administration were significantly higher than those of M group and
      C group (P < 0.05), which recovered to the same level as 1 day before surgery (P
      > 0.05), but on days after 1 hour after administration, there was no significant
      difference when 50% PWT compared with M group or nucleus C group (P > 0.05). NOS
      positive cells and COX-2 positive cells were no significant difference when M
      group compared with C group (P > 0.05). But these positive cells in T6 group were
      significantly lower than those of M group and C group (P < 0.05). CONCLUSION: 50
      microL 2% osthole could completely inhibit the mechanical allodynia in the rat
      model of sciatica induced by lumbar disc herniation when it was administered
      epidurally on 2 or 6 day after surgery. But when administered on 13 or 20 day
      after surgery, its analgesic effect was transient. The effect of 50 microL 2%
      osthole epidural administration on day 6 after surgery on the rat model of
      sciatica induced by lumbar disc herniation may relate to inhibition of the
      expression of COX-2 and NOS in DRG.

PMID- 21954564
TI  - [Pharmacokinetics and bioavailability of Puerarin self-microemulsion in Beagle
      dogs].
AB  - OBJECTIVE: To estabolish a quantitative analysis method for pharmacokinetics and
      bioavailability of Puerarin self-microemulsion in Beagle dogs. METHODS: A
      crossover design was use to detect the pharmacokinetic parameters of Puerarin
      self-microemulsion and suspension in Beagle dogs. The concentration of Puerarin
      in plasma was determined with HPLC, the pharmacokinetics parameters and
      bioavailability was calculated with DAS 2. 1. 1 programs. RESULTS: T(max) of
      Puerarin self-microemulsion and suspension were 3.0 h and 2.0 h, C(max) were 2.14
      mg/L and 1.061 mg/L, AUC(0-24) were 10.642 mg h/L and 3 mg x h/L, respectively.
      The bioavailability of Puerarin self-microemulsion relative to Puerarin
      suspension were 354.73%. CONCLUSION: Puerarin self-microemulsion can
      significantly improve the bioavailability in Beagle dogs.

PMID- 21954565
TI  - [Enhancing effect of volatile oils of rhizoma zingiberis, flos magnoliae and
      fructus litseae on permeation of rotundine in vitro].
AB  - OBJECTIVE: To investigate the enhancing effect of volatile oils of Rhizoma
      Zingiberis (RZ), Flos Magnoliae (FM), Fructus Litseae (FL), Azone and pairwise
      combinations on the permeation of Rotundine in vitro. METHODS: To screen out the
      volatile oils with the best percutaneous enhancing effect on Rotundine, a test of
      penetration through rats skin was conducted by using an improved Franz diffusion
      cell. The accumulative penetration amount of Rotundine was determined by UV and
      HPLC. RESULTS: All of the 3 volatile oils had enhancing effect on Rotundine
      permeation. The average accumulative doses of Rotundine for 8 hours (Q8, mg/cm2)
      of 5% volatile oil of FL, 5% volatile oil of, RZ, 2.5% FL + 2.5% Azone were
      6.0758, 6.1148, 6.5487, the enhancement ratios of 4 hours were 1.01, 1.00, 1.13
      respectively. CONCLUSION: 2.5% FL + 2.5% Azone had the best effect of
      percutaneous enhancing on Rotundine.

PMID- 21954566
TI  - [Studies on preparation and dissolution test in vitro of intragastric floating
      two-chamber osmotic pump tablets of total alkaloids of Coptis chinensis and
      Evodia rutaecarpa].
AB  - OBJECTIVE: To study prescription and technique of intragastric floating two
      chamber osmotic pump tablets (TCOPT) of total alkaloids of Coptis chinensis and
      Evodia rutaecarpa and inspect release property in vitro. METHODS: The orthogonal
      experiment was designed to screen prescription and technique. RESULTS: The
      optimization of prescription and technique were as follows: the expanding agent
      was a mixture of PEO and HPMC as a ratio of 4:1; the osmotic agent in propelling
      layer contained sodium chloride 20 mg, PEG 400 in the cellulose acetate, 10%;
      coating membrane in core tablet, 9%. The release behavior of TCOPT coincidented
      with zero-level equation well and the character of controlled-release was
      transparent. CONCLUSION: TCOPT has good effect of controlled-release in vitro and
      the release behavior in vivo need to be inspected.

PMID- 21954567
TI  - [Optimization of culture conditions for production of extracellular
      polysaccharides by Morchella esculenta].
AB  - OBJECTIVE: To optimize the conditions for exopolysaccharides (EPS) production by
      Morchella esculenta GIM 5.69. METHODS: A Plackett-Burman design was used to
      evaluate the effects of variables factors. The optimal combined conditions for
      maximum polysaccharide production were further optimized by response surface
      methodology. RESULTS: The optimal fermentation conditions were determined as
      follows: glucose 30%, cultivation time 5.98 d, rotary speed 217.44 r/min. The
      average yield of polysaccharide validation experiments was 53.04%, the relative
      error was 1.64%. CONCLUSION: This research has the vital significance regarding
      the Morchella esculenta polysaccharide function of the product development and
      the application.

PMID- 21954568
TI  - [Preparation and pharmaceutical characterization of Marine-SSL].
AB  - OBJECTIVE: To prepare and characterize marine sterically stabilized liposomes
      (Marine-SSL). METHODS: Liposomes were prepared by ethanol injection technique. An
      orthogonal test was utilized to optimize the formulation and preparation of
      Marine-SSL The unencapsulated marine and liposomes were separated by sephadex gel
      G-50, the encapsulation efficiency was detected by HPLC. The morphological
      examination of Marine-SSL was performed using transmission electron microscopy.
      The particle size and Zeta potential of the liposomes were measured. The in vitro
      release rate of marine from liposomes was tested. RESULTS: The liposomes with
      spherical or ellipsoidal shape and better stability featured the encapsulation
      efficiency of (85.39 +/- 1.21)%, the mean partical size of (156 +/- 10) nm, and
      Zeta potential of (- 39.0 +/- 3.06) mv. The release kinetics in vitro obeyed
      Higuchi equation. The stability of Marine-SSL was better. CONCLUSION: The
      selected formulation and preparation technic of Marine-SSL are rational and
      stable and liposomes feature a sustained release in vitro.

PMID- 21954569
TI  - [Research of the essential oil of Plumeria rubra var. actifolia from Laos by
      supercritical carbon dioxide extraction].
AB  - The orthogonal test and the supercritical carbon dioxide fluid extraction were
      used for optimizing the extraction of the essential oil from Plumeria rubra var.
      actifolia for the first time. Compared with the steam distillation, the optimal
      operation parameter of extraction was as follows: extraction pressure 25 MPa,
      extraction temperature 45 degrees C; separator I pressure 12 MPa, separator I
      temperature 55 degrees C; separator II pressure 6 MPa, separator II temperature
      30 degrees C. Under this condition the yield of the essential oil was 5.8927%.
      The components were separated and identified by GC-MS. 53 components of Plumeria
      rubra var. actifolia measured by SFE method were identified and determined by
      normalization method. The main components were 1, 6, 10-dodecatrien-3-ol, 3, 7,
      11-trimethyl, benzoic acid, 2-hydroxy-, phenylmethyl ester, 1, 2
      benzenedicarboxylic acid, bis(2-methylpropyl) ester,etc.. 1, 2
      Benzenedicarboxylic acid, bis (2-methylpropyl) este. took up 66.11% of the total
      amount, and there was much difference of the results from SD method.

PMID- 21954570
TI  - [MRI kidney segmentation based on thresholding and active contour model].
AB  - The proposed hybrid image segmentation method, based on MRI renal images, aims at
      extracting the cortical and medullary regions of the kidney. It incorporates the
      thresholding segmentation and the active contour model. To begin with, the binary
      mask was obtained by preprocessing and thresholding. Then, the manually set
      starting contour deformed like a balloon under the framework of a simplified
      active contour model, thus getting the initial contour of the medulla or the
      cortex. Finally, the initial contour deformed according to the traditional active
      contour model and was attracted by the actual boundary of the tissues, defined by
      the gradient image.

PMID- 21954572
TI  - [A noninvasive and continuous method for blood pressure measurement using pulse
      wave].
AB  - This paper presents a method of noninvasive and continuous measurement of blood
      pressure by pulse wave. The method is realized by extracting the characteristic
      parameters of human brachial artery pulse wave and developing the stepwise
      regression equation. The experiment results showed that blood pressure measured
      by this method was well correlated with which measured by mercury
      sphygmomanometer. The mean difference of blood pressure was smaller than 3 mmHg,
      and the standard deviation was smaller than 5 mmHg.

PMID- 21954571
TI  - [Small-world properties of glucose metabolism based brain functional network].
AB  - OBJECTIVE: To establish a brain functional network of the whole brain based on
      glucose metabolism, and to evaluate the cost and efficiency of the functional
      network. METHODS: 18F-FDG PET of 148 healthy volunteers (30-59 years, n = 148)
      was performed in a resting state. Images were registered to atlas by using the
      statistical parametric mapping (SPM) software. The functional connectivity
      between 90 cortical and sub-cortical regions was estimated by correlation
      analysis. RESULTS: Glucose metabolism brain functional networks had global
      efficiency greater than the lattice but less than the random graph, and local
      efficiency greater than random but less than lattice. This characteristically
      small-world behavior of the brain network was most consistently seen for low-cost
      to medium-cost networks. The small world regime was Cost-[0.0512, 0.5406]. The
      cost efficiency of the networks typically had a maximum positive value when the
      cost was 0.23. CONCLUSIONS: Glucose metabolism brain functional networks have
      economical small-world properties. It is feasible to analyze the functional
      characteristics of human brain by study 18F-FDG PET images. This paper provides a
      new method for studies on brain function.

PMID- 21954573
TI  - [Study on volume measurement of 3-D ultrasound imaging system using fan-scan
      probe].
AB  - This paper addressed the volume measurement of 3D ultrasound imaging system. Two
      different phantoms used in the measurement of volume of the 3D ultrasound imaging
      system were built, i.e., water phantom and agar phantom. The experiments
      demonstrated that as the increase of scan depth, the volume measurement accuracy
      is varied from 4% to 7% in water and 6% to 10% in agar. The phantoms and the
      volume measurement of the 3D ultrasound imaging system provides a basis for the
      establishment of testing standard and clinical application of 3D ultrasound
      imaging system.

PMID- 21954574
TI  - [A virtual visualization system for colon polyp inspection].
AB  - The virtual colonoscopy, virtual flattening and virtual splitting method are
      enhanced by the GPGPU model. The novel virtual eversion method is integrated for
      fast polyp detection. The experimental result showed that the system and various
      visualization methods can represent the colon inner-surface clearly and exactly,
      supporting real-time man-machine interaction. The proposed system is promising in
      human gastrointestinal cancer and polyp inspection.

PMID- 21954575
TI  - [Based on blood vessel edge feature fundus fluorescein angiography image
      splicing].
AB  - According to fundus fluorescein angiography images characteristics, this paper
      proposes a feature based image mosaic vessel edge method. First, detect edge of
      blood vessels by carrying on the pretreatment to the fundus fluorescein
      angiography image in the foundation, wavelet edge detection algorithm. Then, the
      matching method based on chain code feature is described. Finally, a local area
      based on gray level information of the image fusion method is applied to
      angiographic image series. Data processing results show that the method can
      generate an ideal mosaic effect.

PMID- 21954576
TI  - [Preparation of porous ceramic macro-tubes scaffold].
AB  - In this study, a porous hydroxyapatite/tricalcium phosphate (HA/TCP) macro-tubes
      scaffold was fabricated, so that the PU (Polyurethane) can be coated onto the
      scaffold in order to increase the compressive strength.

PMID- 21954577
TI  - [Design of high performance DSP-based gradient calculation module for MRI].
AB  - A gradient calculation module based on high performance DSP was designed to meet
      the needs of digital MRI spectrometer. According to the requirements of users,
      this apparatus can achieve rotation transformation, pre-emphasis, shimming and
      other gradient calculation functions in a single chip of DSP. It then outputs
      gradient waveform data of channel X, Y, Z and shimming data of channel B0.
      Experiments show that the design has good versatility and can satisfy the
      functional, speed and accuracy requirements of MRI gradient calculation. It
      provides a practical gradient calculation solution for the development of digital
      spectrometer.

PMID- 21954578
TI  - [Design of new gas flow detector].
AB  - This paper presents a new gas flow measurement system, which works by
      calorimetric sensors and DSP wavelet transform signal processing. The system is
      achieved by specific hardware including flow sensors, voltage amplifier, A/D
      converter, DSP, heat control circuits as well as supporting software and
      algorithm. The main advantages of the scheme include its high precision, stable
      performance and high noise rejection. It can be applied to especially under small
      tidal volume and low-flow conditions.

PMID- 21954579
TI  - [The research progress of image recognition based on simulated artificial
      vision].
AB  - This review paper presents the current research progress on effect factors of
      image recognition, which was based on simulated artificial vision.

PMID- 21954580
TI  - [Advances in two-photon imaging technology].
AB  - As a new kind of advanced nonlinear imaging approach, two-photon fluorescence
      microscopy technology is wildly used in the field of live cell and tissue
      imaging, especially focusing on long-term dynamic three-dimensional cell imaging.
      This paper firstly presents the principle and characteristic of two-photon
      fluorescence microscopy. Then, the paper focuses on the three key aspects of the
      viability of the specimen, sensitivity of detection, as well as the speed of
      acquisition. In the end, the future prospect of development and application of
      two-phonon imaging technology are predicted.

PMID- 21954581
TI  - [Perspectives on the supervision of medical device software].
AB  - Medical device software is a special kind of medical device, which is different
      from hardware and may introduce more risk. How to reduce the risk of software
      efficiently is the important thing for medical device regulation system. This
      article analyzes medical device software's properties, introduces the status of
      foreign supervision, and finally gives some advises to the related parties.

PMID- 21954582
TI  - [Discussions on the supervision for the post -market contact lenses according to
      the principles of risk management].
AB  - The paper analyses the present situation and problems of the post -market
      situation of contact lenses in China. According to the principles of risk
      management, suggestions for improving the supervision of circulation and
      consumption of contact lenses were given.

PMID- 21954583
TI  - [Sample testing of medical devices in use and the related study].
AB  - Medical equipment is important means and powerful tool in using for disease
      prevention, diagnosis, treatment, care and rehabilitation. It is widely used in
      clinical medicine and daily life. But, the relevant laws and regulations and
      technical capacity is lagging behind, resulted in their use of the process may
      cause harm to patients. In this paper, Guangdong Medical Devices Quality
      Surveillance and Test Institute found the the problems in testing of medical
      devices in use in guangzhou city and in other areas of guangdong province four
      years and summarizes, provide advice how to strengthen and improve in the
      regulation of medical devices in the future.

PMID- 21954584
TI  - [Example of rectification for infusion pump on the radiated emission test].
AB  - This article describes the measure to decrease the emission of a domestic
      infusion pump which can't pass the radiated emission test when performing EMC
      tests. Then optimizes the measure and evaluates whether these measures affect the
      original electrical safety of the pump.

PMID- 21954585
TI  - [The measurement of absolute dose in radiation therapy].
AB  - This article presents and discusses the measurement of absolute dose in radiation
      therapy, aiming to achieve the requires of quality assurance in radiotherapy by
      WHO and enhance the tumor control probability.

PMID- 21954586
TI  - [Application of information management system about medical equipment].
AB  - Based on the practice of workflow, information management system about medical
      equipment was developed and its functions such as gathering, browsing, inquiring
      and counting were introduced. With dynamic and complete case management of
      medical equipment, the system improved the management of medical equipment.

PMID- 21954587
TI  - [The applying of oracle RAC technology in hospital information system].
AB  - This paper describes the RAC installation process and some notes. Comparing with
      HA scheme, RAC Cluster technology can greatly improve the system performance.

PMID- 21954588
TI  - [Temperature and humidity monitoring system of imaging equipment room based on
      wireless network].
AB  - This paper presents a wireless temperature and humidity control system for
      hospital's video room. The system realizes one to multiple communication using
      wireless communication module CC1020 and SHT11 as sensors, and then sets up the
      communication between system and the central station with serial communication
      controller MSCOMM. The system uses VISUAL C++ programming to realize the video
      room temperature and humidity alarm control. It is wireless, efficacious and
      manpower-efficient.

PMID- 21954589
TI  - [Evolution of seed storage globulins and cupin superfamily].
AB  - An extensive superfamily of cupins (clan cl09118) currently combines thousands of
      functionally and structurally diverse prokaryote and eukaryote proteins, which
      contain a beta-barrel of antiparallel beta-strands (cupin module). Possible ways
      of the formation of the cupin superfamily were suggested based on the comparison
      of primary and tertiary structures of proteins from several conserved families of
      cupins including seed storage globulins and plant oxalate oxydases (germins), and
      bacterial oxalate decarboxylases, gentisate dioxygenases and epimerases. The
      origin of two-domain structure of seed storage globulins from cyanobacterial two
      domain oxalate decarboxylases has been deduced. The evolutionary pathway of
      single-domain germins previously suggested to be immediate progenitors of storage
      globulins was traced back. Common evolutionary roots of germins and oxalate
      decarboxylases descend from recent bacterial and archaebacterial proteins whose
      primitive structure is restricted to the cupin module. These root proteins
      reflect the hypothetical structure of a pro-cupin that probably gave rise to at
      least a part of the total diversity of members of the cupin superfamily (for
      instance, to the cupin module of gentisate dioxygenases). The major dilemma for
      the description of the cupin superfamily is distinguishing evolutionary
      divergence from convergence. The structural convergence can be exemplified by
      formation of a beta-barrel inside extremely conserved structures of the otherwise
      unrelated epimerases from Archaea and bacteria.

PMID- 21954591
TI  - Molecular detection and cloning of thermostable hemolysin gene from Aeromonas
      hydrophila.
AB  - Aeromonas hydrophila is a major bacterial pathogen associated with hemorrhagic
      septicemia in aquatic and terrestrial animals including humans. There is an
      urgent need to develop molecular and immunological assays for rapid, specific and
      sensitive diagnosis. A new set of primers has been designed for detection of
      thermostable hemolysin (TH) gene (645 bp) from A. hydrophila, and sensitivity
      limit for detection of TH gene was 5 pg. The TH gene was cloned, sequenced and
      analyzed. The G+C content was 68.06%; and phylogeny was constructed using TH
      protein sequences which had significant homology with those for thermostable and
      other hemolysins present in several bacterial pathogens. In addition, we have
      predicted the four and eight T-cell epitopes for MHC class I and II alleles,
      respectively. These results provide new insight for TH protein containing
      antigenic epitopes that can be used in immunoassays and also designing of
      thermostable vaccines.

PMID- 21954590
TI  - A review of recent experiments on step-to-step "hand-off" of the DNA
      intermediates in mammalian base excision repair pathways.
AB  - The current "working model" for mammalian base excision repair involves two sub
      pathways termed single-nucleotide base excision repair and long patch base
      excision repair that are distinguished by their repair patch sizes and the
      enzymes/co-factors involved. These base excision repair sub-pathways are designed
      to sequester the various DNA intermediates, passing them along from one step to
      the next without allowing these toxic molecules to trigger cell cycle arrest,
      necrotic cell death, or apoptosis. Although a variety of DNA-protein and protein
      protein interactions are known for the base excision repair intermediates and
      enzymes/co-factors, the molecular mechanisms accounting for step-to-step
      coordination are not well understood. In this review, we explore the question of
      whether there is an actual step-to-step "hand-off" of the DNA intermediates
      during base excision repair in vitro. The results show that when base excision
      repair enzymes are pre-bound to the initial single-nucleotide base excision
      repair intermediate, the DNA is channeled from apurinic/apyrimidinic endonuclease
      1 to DNA polymerase beta and then to DNA ligase. In the long patch base excision
      repair sub-pathway, where the 5'-end of the incised strand is blocked, the
      intermediate after polymerase beta gap filling is not channeled from polymerase
      beta to the subsequent enzyme, flap endonuclease 1. Instead, flap endonuclease 1
      must recognize and bind to the intermediate in competition with other molecules.

PMID- 21954592
TI  - [Methylation profiling of human atherosclerotic plaques].
AB  - Somatic mutation theory of atherogenesis proved by alterations at the DNA level
      such as "loss of heterozygosity" and microsatellite instability in
      atherosclerotic plaque is complemented by the date of epigenetic variability of
      genetic loci involved in the pathological process. However, only recently large
      scale analysis of epigenetic modifications in the human genome became possible.
      For the first time quantitative microarray-based methylation profiling of 1505
      CpG-sites across 807 genes was performed in atherosclerotic aorta and carotid
      artery wall lesions using the GoldenGate Methylation Cancer Panel I ("Illumina",
      USA). One hundred and three (7%) CpG-sites in 90 (11%) genes were differentially
      methylated between tissue samples. The most pronounced differences in DNA
      methylation levels were registered for a site which is located in CpG-island of
      imprinted gene H19. By comparing 90 genes that were differentially methylated
      between tissue samples in our study, 10 genes (ICAM1, GSTM1, IGFBP1, POMC, APOA1,
      IL1RN, INS, LTA, MMP3, THBS2) were overlapped with data in Human Genome
      Epidemiology Network (HuGENet), in which they were identified as candidates for
      cardiovascular disease continuum.

PMID- 21954593
TI  - [Freshwater sponge silicateins: comparison of sequences and exon-intron structure
      of genes].
AB  - Siliceous sponge spicules contain silicateins--proteins taking part in biogenic
      silica precipitation and determination of the spicule morphological features. The
      exon-intron structure of four silicatein-alpha isoforms: -alpha1,-alpha2, -alpha3
      and -alpha4 from endemic baikalian sponge Lubomirskia baicalensis was studied.
      For eight sponge species, including both cosmopolitan (Spongilla lacustris,
      Ephydatia muelleri, E. fluviatilis) and Baikal endemic (L. baicalensis, L.
      incrustans, Baikalospongia intermedia, B. fungiformis, Sw. papyracea) species,
      seventeen gene fragment sequences of different silicatein isoforms were
      determined. It was shown that cosmopolitan and endemic Baikalian sponges differ
      from each other by gene structure (have different length ofintrons). Among
      Baikalian sponges silicatein-alpha1 has the most variable intron length, and
      silicatein-alpha4 is the most conservative. Phylogenetic analysis of amino-acid
      silicatein sequences allow identify different silicatein isoforms, which
      authentically differ form four clusters on phylogenetic tree. Phylogenetic
      analysis of exon-intron sequences gives the possibility to separate different
      sponge species in the clusters.

PMID- 21954594
TI  - Differential expression of microRNA-2b with potential target coding P25 in the
      fifth instar larvae posterior silk gland of the silkworm.
AB  - MicroRNAs (miRNAs) are a class of non-protein coding small RNAs that regulate a
      gene expression at the post-transcriptional level. Using in silico screening, we
      found that the 3'-untranslated regions of the P25 gene mRNA are perfectly
      complementary to nucleotides 2-8 at the 5' end of the miRNA-2b (miR-2b). The
      expression of miR-2b and the P25 gene in posterior silk gland of the fifth instar
      larval silkworm was investigated using real-time PCR detection method. The
      results indicated that expression of the P25 gene was very high in the posterior
      silk gland during the fifth instar larvae, whereas a level of miR-2b sharply
      decreased until reaching the lowest one on the 8th day. The expression patterns
      of miR-2b and P25 gene indicate that miR-2b might act as a fine-tuning regulator
      of expression of the P25 gene at the post-transcriptional level.

PMID- 21954596
TI  - [Escherichia coli Dam methylase as a molecular tool for mapping binding sites of
      the yeast transcription factor Rpn4].
AB  - Rpn4p is a transcription factor responsible for coordinated regulation of
      proteasomal genes in Saccharomyces cerevisiae. This factor is involved directly
      or indirectly in regulation of comprise more than one tenth part of all yeast
      genome. Traditional methods are inappropriate for mapping of Rpn4p binding sites
      because of its extremely low concentration in the cell. We have developed the
      model system using Dam-methylase of E. coli which allows to detect interaction of
      Rpn4p with its target genes. In this system we showed that Rpn4p is recruited to
      proteasomal genes only through interactions with DNA.

PMID- 21954595
TI  - [The interplay of transposon silencing genes in the Drosophila melanogaster
      germline].
AB  - Complexes of Piwi proteins and Piwi-interacting RNAs (piRNAs) carry out the
      repression of transposable elements in animal gonads. The Piwi protein clade is
      represented in D. melanogaster by three members: Piwi, Aub and Ago3. Piwi protein
      functions in the nuclei of somatic and germinal ovarian cells, whereas Aub and
      Ago3 are cytoplasmic proteins of germinal cells. Aub and Ago3 interact with each
      other in the perinuclear nuage organelle to perform piRNA amplification via the
      ping-pong mechanism. Previously, derepression of several transposable elements as
      a result of mutations in the piRNA silencing system was shown. Here we quantify
      the increase in expression level of an enlarged number of retrotransposons due to
      the mutations in the piwi gene, nuage components coding aub, mael and spn-E genes
      and the RNA helicase armi gene mutation that impairs Piwi nuclear localization,
      but not the ping-pong cycle. We reveal that piwi, armi, aub, spn-E and mael genes
      participate together in the repression of several transposons (HMS-Beagle, Gate
      and HeT-A), whereas silencing of land G elements requires the same genes except
      piwi. We suggest that Armi has other functions besides the localizing of Piwi
      protein in the nuclei. Our data suggest also a role of cytoplasmic Aub, Spn-E and
      Mael nuage proteins in Piwi-mediated repression of Gate and HMS-Beagle
      transposons in the germline nuclei. As a whole, our results corroborate the idea
      that genome stabilization in the germline is realized by different silencing
      strategies specific for different transposable elements. At the same time, our
      data suggest the existence of yet unknown mechanisms of interplay between nuclear
      and cytoplasmic components of the piRNA machinery in the germline.

PMID- 21954597
TI  - [Prediction of a non-small cell lung cancer sensitivity to cisplatin and
      paclitaxel based on the marker genes expression].
AB  - The goal of the present study was to define gene expression signatures that
      predict a chemosensitivity of non-small cell lung cancer (NSCLC) to cisplatin and
      paclitaxel. To generate set of candidate genes likely to be predictive a current
      knowledge of the pathways involved in resistance and sensitivity to individual
      drugs was used. Forty four genes coding proteins belonging to following
      categories: ATP-dependent transport proteins, detoxification system proteins,
      reparation system proteins, tubulin and proteins responsible for its synthesis,
      cell cycle and apoptosis proteins were considered. Eight NSCLC cell lines (A549,
      Calul, H1299, H322, H358, H460, H292, and H23) were used in our study. For each
      NSCLC cell line a cisplatin and paclitaxel chemosensitivity as well as an
      expression level of 44 candidate genes were evaluated. To develop a
      chemosensitivity prediction model based on selected genes expression level a
      multiple regression analysis was performed. The model based on the expression
      level of 11 genes (TUBB3, TXR1, MRP5, MSH2, ERCC1, STMN, SMAC, FOLR1, PTPN14,
      HSPA2, GSTP1) allowed us to predict the paclitaxel cytotoxic concentration with
      high level of correlation (r = 0.91, p < 0.01). However, none model developed was
      able to reliably predict a sensitivity of the NSCLC cells to cisplatin.

PMID- 21954598
TI  - [Patterns of the histone modifications across the chicken alpha-globin genes
      domain].
AB  - Using native chromatin immunoprecipitation (N-ChIP) followed by TaqMan RT-PCR
      quantitative analysis we have determined the profiles of histone acetylation and
      histone methylation within the alpha-globin gene domain before and after
      switching of embryonic globin genes expression. The results obtained do not
      support a supposition that the inactivation of the embryonic alpha-type globin
      gene pi in erythroid cells of the adult lineage is mediated via formation of an
      inactive chromatin domain. On the other hand we have demonstrated that
      suppression of the gene pi activity in erythroid cells of adult lineage
      correlates with the decrease of the histone acetylation level within the
      embryonic subdomain of the alpha-globin gene domain.

PMID- 21954599
TI  - [Translation termination factor of eRFI of the ciliate Blepharisma japonicum
      recognizes all three stop codons].
AB  - We have determined the type of stop codon specificity of Blepharisma japonicum
      translation termination factor eRF1 in an in vitro reconstituted eukaryotic
      translation system and in in vivo assay (the dual reporter system). We have shown
      that B. japonicum eRF1 retained specificity towards all three stop codons
      although efficiency of peptydyl-tRNA hydrolysis in the presence of UGA is reduced
      in an in vitro assay. We suggest that since the heterotrich B. japonicum
      represents the earliest diverged lineage on phylogenetic tree of ciliates, B.
      japonicum has the universal genetic code as ancestor group for all ciliates.

PMID- 21954600
TI  - [Leishmania donovani: structural insignt in the recognition of C-methylated
      analogues of spermidine as natural polyamine].
AB  - The ability of alpha-, beta-, gamma- and omega-methylated spermidine analogues to
      restore the growth of L. donovani promastigotes that were depleted of putrescine
      and spermidine was investigated. Only beta-methylated spermidine, like natural
      spermidine was capable of restoring the growth of L. donovani, while the
      remaining three analogues turned out to be inactive. Considering that alpha
      methylated spermidine is a functionally active spermidine surrogate both in vivo
      and in vitro, this analogue can be considered as an antidote in the host-parasite
      system, especially in cases where inhibitors of polyamine biosynthesis are used
      for the therapy of leishmaniasis.

PMID- 21954601
TI  - [Prothymosin alpha interacts with C-terminal domain of histone H1 and dissociates
      p53-histone H1 complex].
AB  - A novel mode of the tumor suppressor protein p53 regulation, mediated by
      recruitment of the linker histone H1 to the promoters of p53 target genes leading
      to specific repression of p53-dependent transcription, has recently been
      uncovered. Yet, how this repression could be relieved is not clear. Previously, a
      histone-binding nuclear protein prothymosin alpha (ProTa) was shown to trigger a
      p53 response. The histone-binding region of ProTa was found to be essential for
      this effect, raising a possibility that ProTa stimulates p53-dependent
      transcription by dissociating the p53-histone H1 repressive complex. Here, we
      have shown that ProTa interacts with the same C-terminal domain of histone H1 as
      p53 does and, therefore, ProTa and p53 could compete for binding to histone H1.
      Furthermore, ProTa, when competent for histone H1 binding, is able to liberate
      p53 from the histone H1-p53 complex in vitro. In vivo, stimulation of p53
      dependent transcription by ProTa correlates with ability of ProTa to interact
      with histone H1. Ectopic expression of histone H1 or its C-terminal ProTa-binding
      domain specifically suppresses the stimulating effect of ProTa on transcription
      of the p53-responsive reporter gene in cultured cells. These results are
      consistent with the model that ProTa may enhance p53 transcription activity by
      displacement of histone H1 from p53-H1 repressive complex.

PMID- 21954602
TI  - [Disordered regions in C-domain structure of influenza virus M1 protein].
AB  - Influenza virus matrix M1 protein is one of the main structural components of the
      virion performing also many different functions in infected cell. X-ray analysis
      data with 2.08 angstrom resolution were obtained only for the N-terminal part of
      M1 protein molecule (residues 2-158) but not for its C-terminal domain (159-252).
      In the present work M1 protein of A/Puerto Rico/8/34 (H1N1) virus strain in
      acidic solution was investigated with the help of tritium bombardment. Tritium
      label incorporation into M1 protein domains preferentially labeled the C-domain
      and inter-domain loops. Analytical centrifugation and dynamic light scattering
      experiments demonstrated increased hydrodynamic parameters (diameter) that may be
      explained by low degree of M1 structural organization. Computational analysis of
      M1 protein by intrinsic disorder predictions methods also demonstrated the
      presence of unfolded regions mostly in the C-domain and inter-domain loops. It is
      suggested, that influenza virus M1 polyfunctionality in infected cell is
      determined by its tertiary structure plasticity which in its turn results from
      the presence of unstructured regions.

PMID- 21954603
TI  - [Thermodynamics of calmodulin and tubulin binding to the vinca-alkaloid
      vinorelbine].
AB  - Vinca-alkaloids, such as vinblastine, and some of their derivatives, as for
      example vinorelbine, are widely used in clinical therapy of leukemia and several
      types of tumors. Their effects are associated with the disfunctioning of the
      mitotic spindle, which leads to mitosis blockage and a shutdown of the cell
      cycle. Their primary target is tubulin, however recent research has shown that
      some of the vinca-alkaloids inhibit calmodulin binding to its targets. Vinka
      alkaloids binding with other proteins could be responsible for their efficiency
      and neuroprotection. Here we investigated the thermodynamics of vinorelbine
      interactions with calmodulin and tubulin. It was determined that unlike the other
      vinca-alkaloids both vinorelbine binding sites are located in the C-domain of
      calmodulin, and characterized by association constants of 4.0 x 10(5) and 5.4 x
      10(4) M(-1). At the same time the thermodynamics of vinorelbine binding to
      tubulin are not much different from that of other vinca-alkaloids. These results
      will allow getting a better insight on the reaction mechanisms of vinca-alkaloids
      on a secondary protein target.

PMID- 21954604
TI  - [Endo-alpha-1-4-polygalactosaminidases and their homologues: structure and
      evolution].
AB  - Endo-alpha-1,4-polygalactosaminidase is a rare enzyme. Its catalytic domain
      belongs to the GH114 family of glycoside hydrolases. Phylogenetic analysis of the
      family proteins allowed us to show an important role of duplications,
      eliminations, and horizontal transfer in the evolution of their genes. Domain
      structure, the secondary structure, and proposed structure of the active center
      of the endo-alpha-1,4-polygalactosaminidases are discussed. Evolutionary
      connections of the GH114 family with GH13, GH18, GH20, GH27, GH29, GH31, GH35,
      GH36, and GH66 families of glycoside hydrolases, as well as, with COG1306,
      COG1649, COG2342, GHL3, and GHL4 families of enzymatically uncharacterized
      proteins have been revealed by iterative screening of the protein database. The
      unclassified homologues have been grouped into 13 new families of hypothetical
      glycoside hydrolases: GHL5 - GHL15, GH36J, and GH36K.

PMID- 21954605
TI  - [Regulation of multidrug resistance genes by transcriptional factors from the
      BltR subfamily].
AB  - BltR is a MerR family transcriptional factor, experimentally characterized in
      Bacillus subtilis. It activates transcription of genes encoding multidrug
      transporter Blt and spermine/spermidine acetyltransferase BltD. Here we studied
      BltR dependent regulons in 25 bacterial genomes using the comparative genomic
      approach. The structure of the promoter regions of regulated genes is typical for
      MerR family activators: the binding sites are located in long spacers between
      promoter elements. Regulated genes are usually co-localized with regulator genes
      and are divergently transcribed with them. The studied transcriptional factors
      regulate the transcription of multidrug transporter and spermine/spermidine
      acetyltransferase genes. These transporters can be either secondary or ATP
      dependent. The phylogenetic analysis demonstrated that their role as multidrug
      transporters is conserved.

PMID- 21954606
TI  - [Machine learning study of DNA binding by transcription factors from the LacI
      family].
AB  - We studied 1372 LacI-family transcription factors and their 4484 DNA binding
      sites using machine learning algorithms and feature selection techniques. The
      Naive Bayes classifier and Logistic Regression were used to predict binding sites
      given transcription factor sequences and to classify factor-site pairs on binding
      and non-binding ones. Prediction accuracy was estimated using 10-fold cross
      validation. Experiments showed that the best prediction of nucleotide densities
      at selected site positions is obtained using only a few key protein sequence
      positions. These positions are stably selected by the forward feature selection
      based on the mutual information of factor-site position pairs.

PMID- 21954607
TI  - [Identification of proteins overexpressed in malignant gastric tumors: comparison
      of the results of 2-De and bioinformatics search].
AB  - Comparison of protein expression in intestinal and diffuse stomach tumors by 2D
      gel electrophoresis led to identification of three proteins (SOD2, S100A6, and
      TXN), which are overexpressed in tumors as compared to normal controls. It was
      shown, that overexpression of proteins SOD2 and TXN occurs much more frequently
      in diffuse tumors than in intestinal ones. A control panel of eleven proteins
      overexpressed in stomach tumors has been selected based on the data of
      comparative 2D analysis described in the literature. Bioinformatics search for
      mRNAs encoding proteins from the control panel in Oncomine database (which
      contains the results of determination of mRNA transcription level in tumor vs.
      normal samples) demonstrated the coincidence of proteomic and transcriptomic data
      for seven out of 11 proteins.

PMID- 21954608
TI  - High level secretory expression of murine ocil by CHO cells and action of OCIL on
      osteoclast differentiation.

PMID- 21954609
TI  - [The hypothalamic-pituitary-adrenal axis and genetic variants affecting its
      reactivity].
AB  - The hypothalamic-pituitary-adrenal (HPA) axis plays a primary role in the body
      response to stresses. Activation of the HPA axis results in the production
      ofcorticosteroid hormones that influence a wide variety of body functions,
      including immunity, metabolism, ion exchange, and behavior. A well-balanced
      regulation of stress responses is pivotal for maintaining intrabody homeostasis.
      The HPA axis is regulated at several levels, including stimulatory or inhibitory
      signals from the brain mediated through neurotransmitter systems and the
      suppressive feedback influence of corticosteroids themselves. Corticosteroids
      affect the HPA axis through binding to the glucocorticoid and mineralocorticoid
      receptors located in the hippocampus. Genes encoding these receptors have several
      polymorphic regions in which the alleles are associated with different basal and
      stress-induced levels of hormones secreted in the course of HPS axis stimulation.
      Additionally, genetic variants of neurotransmitter systems involved in the
      activation or suppression of the HPA axis have been found. Thus, the given
      genetic variations are major contributors to the HPA axis-mediated individual
      resistance or susceptibility to stresses.

PMID- 21954610
TI  - [The influence of morphogene Wg on the formation of an ectopic eye in Drosophila
      melanogaster].
AB  - Due to the ectopic expression of the ey gene in the wing imaginal disc under the
      action of the 1096-Gal4 driver, a part of the wing disc cells change their fate
      and become eye cells. Ectopic eyes are induced in definite regions of the wing
      disc and form a stable pattern on the wing of an adult fly. Here, we have shown
      that the ectopic expression of Wg inhibits the formation of ectopic eyes, and
      conversely the expression of Wg is reduced in the sites of ectopic Ey expression.
      Experiments with overexpression of the vesicular traffic protein H rs capable of
      inhibiting the Wg signaling agree with the notion on antagonism of Wg and Ey in
      ectopic eyes. Our results confirm that the processes of formation of normal and
      ectopic eyes are principally similar with regard to genetic control.

PMID- 21954611
TI  - [Transcriptional analysis of the Grp gene, a genomic homolog of the
      retrotransposon gypsy gag gene, in Drosophila melanogaster].
AB  - In the present work, we studied the Grp gene (CG4680, Gag related protein)
      expression at the transcriptional level. It was found that at the embryonic and
      larval stages of D. melanogaster development the Grp expression proceeds at a low
      level, but it significantly increases at the adult stage. Adult individuals
      display a tissue-specific expression: an eleveated level of transcription is
      observed in the gut tissues, but not in the chitin carcass, head, and gonads.
      Since the gut may potentially be a primary barrier for the penetration of a viral
      infection, we conducted a comparative analysis of Grp gene transcription in D.
      melanogaster strains differing in the presence of active copies of the gypsy
      errantivirus and in the status of the flamenco gene controlling sensitivity to
      errantiviral infections. No noticeable differences in the level of Grp gene
      transcription were revealed. Thus, the Grp gene is not a pseudogene, but it is a
      functional gene of the D. melanogaster genome whose role remains to be
      elucidated.

PMID- 21954612
TI  - [Distant interactions between enhancers and promoters in Drosophila melanogaster
      are mediated by transgene-flanking Su(Hw) insulators].
AB  - Insulators are DNA elements modulating gene activation by enhancers. Interaction
      between insulators can result in either isolation, or activation of promoter by
      the enhancer. In the present study, it is demonstrated that in transgenic lines,
      the yellow enhancers are unable to activate promoter of the tagged gene through
      the mini-white gene. The mini-white promoter, which functions as an insulator,
      can block the enhancer activity. In case that the genes and regulatory elements
      in the construct are flanked by Su(Hw) insulators from retroposon MDG4,
      interaction between enhancers and the yellow promoter is restored. The data
      obtained are congruent with the model suggesting that promoters can function as
      insulators, and that interaction between the insulators facilitates the
      interaction between enhancers and promoters within transcriptional domain.

PMID- 21954613
TI  - Morphological and physiological characteristics of transgenic cherry tomato
      mutant with HBsAg gene.
AB  - HBsAg gene was previously introduced into cherry tomato (Lycopersicum esculentum
      var. cerasiforme) by Agrobacterium-mediated transformation. To investigate the
      side effect of HBsAg gene in cherry tomato, we analyzed morphological and
      physiological characteristics of the transgenic mutant N244. The process was
      performed under field conditions. The results suggested that the mutant N244
      exhibited morphological, cytological and physiological variation. First of all,
      compared with the wild plants NK, N244 had fleshy and dark green leaves, the
      fewer notches of leaf edge, more adventitious roots and barren seeds. Moreover,
      the chromosome of N244 were found to be triploid (n = 36) by flow cytometric
      analysis. Furthermore, N244 has obvious physiological alterations, as compared to
      NK. It was speculated that transformation of the genes probably led to ploidy
      variation, and further caused phenotype and physiological changes of plants. Our
      study will reveal side effects of the mutants, and promote cultivation of
      transgenic plants in the field.

PMID- 21954614
TI  - [Variability and phylogenetic relationships of the Cucumis sativus L. species
      inferred from NBS profiling and RAPD analysis].
AB  - Genetic variability of the Cucumis sativus species and its phylogenetic
      relationsips with other species of the genus were studied on the basis of RAPD
      marking and analysis of intra- and interspecific polymorphism of the nucleotide
      sequences of the NBS-LRR gene family in species of the genus Cucumis with the use
      of the NBS profiling method. According to RAPD analysis, cucumber cultivars from
      different geographic regions are highly similar, except for accessions k-3835 and
      k-3833 from Afghanistan. NBS profiling analysis revealed phylogenetically most
      distinct accessions expected to be characterized by specificity of resistance: k
      3845 from Uzbekistan, k-3851 from Kyrgyzstan, line 701, k-3835 and k-3833 from
      Afghanistan, k-2757 and k-3079 from Netherlands, vr.k. 908 from Canada, k-2926
      from Bulgaria, Russian cultivars Monastyrskii, Izyashchnyi, and Lel'. Three
      essentially different groups of species were distinguished, and the C. sativus
      species (subgenus Cucumis) was found to be distant from the species belonging to
      the subgenus Melo.

PMID- 21954615
TI  - [Preferential elimination of chromosome 5R of rye in the progeny of 5R5D
      dimonosomics].
AB  - Transmission of chromosome 5R of rye (Secale cereale L.) and chromosome 5D of
      common wheat (Triticum aestivum L.) through gametes of 5R5D dimonosomics (2n =
      42, 20W" + 5R' + 5D') was studied. Chromosome 5R was found to have lower
      competitiveness as compared to 5D. Gametes with the rye chromosome were two times
      less often involved in the formation of a progeny. The combined frequency of the
      karyotypes of wheat (5D5D) and wheat monosomics (5D) was 11.6-fold higher than
      the frequency of the karyotypes of substitution lines (5R5R) and monosomics for
      the rye chromosome (5R). The karyotypes of 10.38% of hybrid plants had aberrant
      5R chromosomes with different translocations formed as a result of breakages in
      the centromere and in the proximal region of the long arm. Telocentrics for the
      short arm (t5RS), i5RS isochromosomes, and chromosomes with a terminal deletion
      T5RS.5RL-del were identified. The absence of amplification of SSR markers mapped
      on 5RS and the detection of PCR products for a number of 5RL markers (ineluding
      the genome-specific rye marker Xrms115) permitted nine plants carrying only the
      long arm of chromosome 5R to be revealed. Since t5RL telocentrics were not
      detected by the cytological analysis, the results obtained allow us to suggest
      the presence of small intercalary translocations of the long arm of chromosome 5R
      in chromosome 5D or in other wheat chromosomes.

PMID- 21954616
TI  - [Karelian birch (Betula pendula Roth. var. carelica Merkl.) as a model for
      studying genetic and epigenetic variation related to the formation of patterned
      wood].
AB  - The results of long-term pioneering studies on in vitro micropropagation of
      Karelian birch patterned forms and simultaneous cytological analysis of plants
      multiplied using different periods of in vitro culturing are published for the
      first time. The patterned wood character has been shown to be correlated with the
      degree of mixoploidy of its somatic tissue, which is higher in the plants
      obtained from callus cultures during the first years of culturing. Subsequent
      intracellular selection leads to a decrease in mixoploidy and, hence, in a later
      expression and lower expressivity of the patterned wood character in regenerant
      plants. It is also known that extreme growth conditions stimulate the formation
      of patterned wood. Thus, Karelian birch may serve as a model object for studying
      the forms of variability (both genetic and epigenetic) that result in patterned
      wood. The genetic variability is expressed in the variation of the degree of
      mixoploidy of somatic tissue as a result of various mitotic aberrations. The
      epigenetic variability is not related to changes in the DNA structure; it is
      caused by different phenotypic effects of genes located in cells with different
      ploidy/aneuploidy levels, the ratio between which varies depending on the
      environmental conditions. The expression of genes, in particular, rRNA genes, is
      affected by extreme conditions. The appearance of a residual nucleolus at the
      mitotic metaphase-telophase stages is a cytological expression of this
      phenomenon.

PMID- 21954617
TI  - [Genetic divergence and relationships among smelts of the genus Osmerus from the
      Russian waters].
AB  - Smelts of the genus Osmerus, O. eperlanus and O. mordax dentes, inhabiting the
      basins of the Atlantic, Arctic, and Pacific oceans were investigated using RFLP
      analysis of the mitochondrial DNA segments A8/A6/COIII/ND3 and ND3/ND4, and
      sequencing of the cytb and COI genes (mtDNA), and intron 1 of the rpS7 gene
      (nDNA). A total of 14 samples from the populations from most part of the Russian
      range were examined. The mean values of haplotype and nucleotide diversity
      constituted 0.5997 +/- 0.11264 and 0.003201 for O. m. dentex, and 0.3086 +/-
      0.09892 and 0.000431 for O. eperlanus, respectively. The high level of
      interspecific diversity (12.94%) along with the low level of intraspercific
      diversity (0.049% for O. m. dentex, and 0.001% for O. eperlanus was observed. The
      dendrograms (UPGMA, NJ, MP, and BA) constructed using the data of RFLP analysis
      of mtDNA, along with the sequencing data of mitochondrial and nuclear genes were
      congruent. The representatives of O. eperlanus and O. m. dentex formed steady
      clusters in accordance with their species affiliation, albeit without subdivision
      into local populations depending on their geographic locality.

PMID- 21954618
TI  - Genetic diversity among Balkan trout populations based on RAPD analysis.
AB  - Random amplified polymorphic DNA (RAPD) markers were used to estimate the
      population structure and phylogenetic relationships among samples of the Salmo
      trutta complex that inhabit the Balkan Peninsula. Five random oligodecamers were
      selected to amplify DNA from 140 fish from seven populations. Using these
      primers, 55 discernible DNA fragments were generated, of which 50 (90.91%) were
      polymorphic. The statistical results indicated that there was low genetic
      diversity within populations (with an average percentage of polymorphic bands (P)
      of 11.69% and a Nei's genetic diversity index (h) of 0.035), but at the same time
      high genetic differentiation among populations (F(ST) = 0.89). The distribution
      of genetic diversity among Balkan trout may result from their evolutionary
      history and reflects genetic drift coupled with bottleneck phenomena. Overall,
      RAPDs proved valuable tools for quick and reliable stock discrimination and
      provided information that might be useful regarding conservation and management
      of trout.

PMID- 21954619
TI  - [Adaptive intraspecific divergence: an example using the animal cytochrome b
      gene].
AB  - The topologies of phylogenetic trees characterized by a high level of
      intraspecific divergence between the phylogenetic DNA groups (clades) are often
      explained in terms of the theory of Pleistocene refugia. To elucidate the issue
      of the adaptive role of intraspecific divergence, the changes in the
      physicochemical properties of amino acids in the course ofcladogenesis (MM01
      model of the TreeSAAP 3.2 package) were analyzed in this work using as an example
      the nucleotide sequences of the cytochrome b gene in some species of northern
      animals (lemmings, redbacked voles, chipmunks, flying squirrels, ermines). It was
      shown that the process of intraspecific divergence was rarely accompanied by
      radical amino acid substitutions in cytochrome b caused by adaptation
      (directional selection). In connection with this, the hypothesis is discussed
      according to which the adaptive variants formed in the species at the peak of
      cold were lost with climatic warming due to the drift or selection against
      individuals adapted to cold.

PMID- 21954620
TI  - [Inheritance of longitudinal shell bands in the snails Littorina obtusata and
      Littorina saxatilis (Gastropoda, Prosobranchia)].
AB  - The hypothesis of a monogenic inheritance of dark longitudinal bands on the shell
      in the gastropods Littorina obtusata and L. saxatilis was checked. One gene
      having two alleles proved to be responsible for the shell banding pattern in both
      of the species. The presence of bands was a dominant character in either case.

PMID- 21954621
TI  - Molecular cloning, expression, and imprinting status of maternally expressed gene
      8 (Meg8) in dairy cattle.
AB  - At present, small number imprinted genes have been reported in cattle compare to
      human and mouse. Maternally expressed gene 8 (Meg8), a non-coding gene, have been
      identified maternally expressed in mouse and sheep, but its sequences and
      imprinting status have not been established in cattle. In this study, the full
      length of cattle Meg8cDNA sequence was obtained by reverse transcript polymerase
      chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE) method, which
      has a high homology in exons sequences with the corresponding region of sheep
      Meg8. The isolation of cDNA sequence showed the presence of multiple splice
      variants in cattle Meg8 gene. The Meg8 was found to be expressed in all adult
      examined tissues, including heart, liver, spleen, lung, kidney, brain,
      subcutaneous fat and skeletal muscle. A single nucleotide polymorphism (SNP) was
      identified in exon 6 by Single-Strand Conformation Polymorphism (SSCP), and used
      to distinguish between monoallelic and biallelic expression in cattle tissues.
      The expression analysis of Meg8 in a heterozygous cattle showed that only one
      parental allele was expressed in all examined tissues, suggesting that Meg8 is
      imprinted in cattle.

PMID- 21954622
TI  - [Endogamy and isolation by distance in the Tatarstan population].
AB  - A total sample of 31 837 marriage records made in 13 raions (districts) of
      Tatarstan in 1990-2000 have been used to determine the endogamy index and
      parameters of Malecot's isolation by distance model. The endogamy index varied
      from 0.45 in Pestrechinsky raion to 0.74 in Aktynashsky raion. The parameters of
      Malecot's isolation by distance model varied in Tatars as follows: random
      inbreeding, from 0.00014 to 0.00076; root mean square migration, from 46 to 110
      km.

PMID- 21954623
TI  - [Comparative analysis of the informativeness of ISSR markers for estimating
      genetic diversity of horse breeds].
AB  - The informativeness of six different types of ISSR markers was compared in order
      to evaluate genetic diversity of Mongolian, Buryat and Tuvinian horse breeds
      (Equus caballus). The dinucleotide-based ISSR primers ((GA)9C, (AG)9C, and
      (CA)9G) proved to be of little use to examine genetic polymorphism among horses
      due to the low number of amplified and polymorphic fragments. The polymorphism
      information content (PIC) for the dinucleotide-based ISSR primers was 2.88 times
      lower than that for trinucleotide-based ISSR markers. Among the trinucleotide
      based ISSR markers, CAC ISSR marker was also found to be noninformative, due to
      the low number of polymorphic loci identified. The highest values of the
      polymorphism information content (PIC) were obtained for two types of ISSR
      markers, based on (GAG)6C (PIC, 3.61) and on (ACC)6G (PIC, 2.50). Thus, the
      results of the present study showed that GAG and ACC ISSR markers were most
      informative for evaluation of genetic diversity among horses.

PMID- 21954624
TI  - Association between polymorphism in bovine PRKAG3 gene and milk production
      traits.
AB  - The aim of the conducted study was to evaluate correlation between genotypes and
      PRKAG3 compound genotypes and milk production traits (yield of milk, milk fat and
      milk protein, and protein and fat content in milk). The study covered a herd of
      180 Jersey cows. PCR-RFLP method was used for genotyping. The frequencies of
      alleles that occur mostly and combined genotypes were as follows: T1526G G -
      0.57, G 1609A G - 0.92 and for T1526G/G1609A TG/GG - 0.54. The results obtained
      in the study demonstrated the correlation between analyzed genotypes and selected
      milk production traits; however they are not statistically significant.

PMID- 21954625
TI  - [Expression profiling of candidate genes for abdominal fat mass in domestic
      chicken Gallus gallus].
AB  - The quantitative traits of mass and percentage of abdominal fat in chicken and
      various types of obesity in mammals are homologous and functionally similar.
      Therefore, the genes involved in obesity development in humans and laboratory
      rodents as well as those responsible for pig lard thickness could be involved in
      abdominal fat deposition in broilers. Expression of candidate genes FABP1, FABP2,
      FABP3, HMGA1, MC4R, PPARG, PPARGC1A, POMC and PTPN1 was studied in fat, liver,
      colon, muscle, hypophysis, and brain in chicken (broilers) using real-time PCR.
      Significant difference in the HMGA1 gene expression in the liver of broiler
      chicken with high (3.5 +/- 0.18%) and low (1.9 +/- 0.56%) abdominal fat
      concentration has been revealed. The expression of this gene was been shown to
      correlate with the amount (0.7, P < or = 0.01) and mass (0.7, P < or = 0.01) of
      abdominal fat. The PPARG gene expression in liver in the same chicken subsets was
      also significantly different. Correlation coefficients of the gene expression
      with the abdominal fat amount and mass were respectively 0.55 (P < or = 0.05) and
      0.57 (P < or = 0.01). Based on these results, we suggest that the HMGA1 and PPARG
      genes are involved in abdominal fat deposition. The search for single nucleotide
      polymorphisms (SNPs) in the HMGA and PPARG regulatory regions could facilitate
      identifying genetic markers for broiler breeding according to the mass and
      percentage of abdominal fat.

PMID- 21954626
TI  - [Development of a sex-specific molecular marker for Japanese hop Humulus
      japonicus Siebold & Zucc].
AB  - Japanese hop (Humulus japonicus Siebold & Zucc.) is a dioecious plant and a
      suitable model for studying the XX/XY1Y2 system of sex chromosomes. To develop a
      sex-specific marker, 12 RAPD and 36 ISSR markers were analyzed on the basis of
      pools of male and female plants identified after flowering. We were the first to
      identify ISSR marker K-16, which manifested stable amplification of an
      approximately 300-bp fragment in male plants and the absence of amplification in
      female plants in the populations examined. Marker effectiveness was confirmed in
      several Japanese hop populations of different origin.

PMID- 21954627
TI  - [Longevity control in fungi and other organisms. The conception of scales].
AB  - The review deals mainly with gerontological processes that occur on the cellular
      colonial level of organization in fungi and cellular-tissular level in other
      organisms. Aging and anti-aging mechanisms operating on these levels of
      organization can be considered as common ones for all living things. Fungi, as an
      object with tissular-like organization of thallus, afford a broad spectrum of
      possibilities as to solving the tasks of general gerontological import. Three
      basic (chronological, replicative, and cell-suicidal) and several auxiliary
      mechanisms of aging are singled out, the classification is given of stochastic
      aging factors accumulating in cells. It is shown that in complex multi-cellular
      organisms, aging and anti-aging mechanisms operate on the level of interactions
      between tissues, though in the base of their actions lie the aforesaid
      conservative basic mechanisms. Preliminary generalized conception of aging--the
      conception of scales--is put forward that is founded on the model of balanced and
      non-balanced counteractions between stressful impacts and various mechanisms of
      aging and anti-aging with different extent of genetic preprogramming. The
      importance is reaffirmed of mycological gerontology contribution to broadening of
      inferences on aging nature.

PMID- 21954628
TI  - [The ants: a strategy of population concentration].
AB  - Ants are provided with a balanced system of reactions either to the original
      paucity of socia or to their secondary depopulation. This system can be defined
      as a strategy of population concentration. Both a successful reproduction of
      workers and queen fertilization are necessary conditions for ant communities'
      survival and development. Thus, the anthills must be large enough to ensure
      optimal conditions for reproduction. It is the strategy of population
      concentration that is directed to an accelerated attainment (or rehabilitation)
      by a socium of a state of stable development by way of concentrating the existent
      ant staff in an accessible number of viable nests. This strategy is realized
      throughout the life of ant communities by way of (a) fusing the starting family
      cells left by founder females, (b) fusing small anthills during artificial ant
      migrations, (c) uniting smaller socia or their joining other anthills, (d)
      reintegrating the secondary anthills (fragmentants) after an exogenous
      fragmentation of formicaries. Pooling and the attraction of deficient demographic
      resources from outside form the most efficient and quickest ways of reaching or
      restoring the threshold density levels. By realizing this strategy, the ants
      solve their paramount problems of anthill or settlement conservation at any
      particular time, as well as of providing some prospects for ant existence in the
      future. These problems are so vital for ant socia that they appear to hold
      priority over such other characteristics of utmost importance as genetic kinship
      or even species identity. The priority of social basics over genetic ones is
      unequivocally supported through mixed formicaries. A necessary condition for the
      realization of the strategy of population concentration is tolerance of highly
      developed social systems to the diversity of forms and to deviations from the
      norm. The use of one and the same mechanism at all stages of the life both of an
      individual socium and large ant settlements is evidence of the universality of
      this strategy, as well as of its unconditioned importance to the life of ant
      communities.

PMID- 21954629
TI  - [Spatial organization of felids populations and some traits of their reproductive
      strategies].
AB  - In all Felidae species, females are able to mate with several males during the
      estrus. Promiscuity mating system is the most typical of the solitary living
      species that have large home ranges. Females are usually widely distributed over
      the area and males move actively searching for the receptive females and
      defending them during the estrus period. Mating with few males is usually
      considered as a possibility to improve the quality of the offspring. In this
      article, some characteristics of home range use, marking and acoustic activity,
      traits of physiology which may result in promiscuity mating in felids are
      considered. An adaptive significance of mating few males is also discussed.

PMID- 21954630
TI  - [Contemporary concepts of homology in biology (a theoretical review)].
AB  - A brief review of the contemporary theoretical concepts of homology being
      developed basically in systematics and phylogenetics as well as in developmental
      biology is presented. Ontologically, both homology and analogy represent a kind
      of correspondence considered from the standpoint of nominalism, realism, and
      conceptualism. According to their nominalistic treatment, both are described by a
      set-theory approximation which makes them classes (in the logical sense). The
      realistic treatment provides their holistic view according to which a homologue
      is an anatomical or evolutionary singular while analogue remains a class. The
      conceptualistic treatment means that there are real (objective) correspondences
      existing among real (objective) entities while fixation of any of them is based
      on certain theoretical presumptions adopted by a researcher; homology as a
      natural kind (including homeostatic property cluster) seems to be most consistent
      with such a treatment. Realistic view of homology makes it "absolute", while two
      others make discrimination of homology and analogy strictly relative. Two basic
      general homology concepts have been developed in recent literature--taxic and
      transformational ones; the first considers respective correspondences as
      structure relations, the second as process relations. The taxic homology is
      nearly the same as classical typological one (Owen), while transformational
      homology unites all its phylogenetic, ontogenetic (developmental) and
      transformation-typological definitions. Process-structuralistic approach seems to
      unite both taxic and transformational ones. The latter makes it possible to apply
      general homology concept not only to structures but to processes as well. It is
      stressed that homology is not identical to the similarity, the latter being just
      the means for revealing the former. Some closer consideration is given to
      phylogenetic, ontogenetic and genetic treatments of homology; significant
      uncertainty is shown to exist between them which causes the "homology problem".
      Epistemologically, any homology statement has a status of hypothesis which makes
      such a statement theory-dependent according to the hypothetic-deductive
      argumentation scheme. This dependence allows to stress once more the relative
      nature of homology and analogy correspondences. Some questions concerning
      operational concepts and criteria of homology are considered. A hierarchical
      concept of homology seems to be the most promising prospect of future development
      of the "homology problem".

PMID- 21954631
TI  - The prospects of medical application of metal-based nanoparticles and
      nanomaterials.
AB  - Current studies, dedicated to metallic (gold, silver, iron, and copper)
      nanomaterials are reviewed in this paper. This metals own unique physical and
      chemical properties which determine their application. The medical application of
      metallic nanomaterials includes therapy and prophylaxis of diseases, development
      of new drugs and improvement of conventional ones, nanodiagnostics. Nevertheless
      some aspects concerning the introduction of the nanometals into medical practice
      need further profound research.

PMID- 21954632
TI  - Functional state of the respiratory and immune system in children-residents of
      the radioactive contaminated territories.
AB  - More then 25 years after the Chernobyl accident, a higher prevalence of bronchial
      hyperreactivity, reduced lung function, and increased levels of free radicals in
      exhaled breath condensates (EBC) were observed in children residing in
      radioactive contaminated territories. Comparing children with different
      residential radiation background, this study investigated fatty acids of EBC
      using gas liquid chromatography, counts of B-lymphocyte antigen CD19 in T-cell
      (CD3) and phagocytotic activity of neutrophils in blood samples. Regarding EBC,
      we demonstrate that lipid peroxidation was activated, antioxidant properties of
      pulmonary surfactant were decreased, were detected metabolic disorders of
      essential fatty acids at the stage of bioregulators-eicosanoids formation.
      Regarding the immune function of blood cells, we found a decrease of the
      proportions of CD3+ 19- and CD3- 19+ lymphocyte subpopulations and an unbalance
      of their numbers. Also the phagocytotic activity of neutrophils was reduced in
      higher exposed children. Children living in the radioactive contaminated
      territories have more alterations of surfactant properties and immune activities,
      which may contribute to an increased risk of respiratory problems. This research
      was supported by grants from the U.S. Civilian Research and Development
      Foundation (UKB1-2929-KV-08).

PMID- 21954633
TI  - Clinical application of magnetic mapping.
AB  - Noninvasive screening technique to identify cardiac disease in its early phase is
      developed. Magnetic imaging of cardiac action currents is a new and an ideally
      suited technology for testing the level of local electric heterogeneities of
      myocardium. Magnetocardiography has the potential to make a valuable contribution
      in basic examination and analysis of biosignals of a heart. in particular whilst
      all vector components are used, vast spatial coverage and excellent signal
      quality.

PMID- 21954634
TI  - [Relationship of silent myocardial ischiemia with the course of rheumatoid
      arthritis and hyperhomocysteinemia].
AB  - The aim of this investigation was to study the frequency and duration of silent
      myocardial ischemnia (SMI) and to evaluate its relationship with the duration of
      rheumatoid arthritis (RA) and hyperhomocysteinemia. 63 patients with rheumatoid
      arthritis were observed, during this study we investigated homocysteine blood
      level, markers of an inflammation and episodes of SMI using daily (cholter) ECG
      monitoring. It was often recorded "silent" myocardial ischemia in patients with
      the RA, which was associated with high activity of inflammatory process (high C
      reactive protein, the disease activity score, HAQ, number of swollen and painful
      joints) and hyperhomocysteinemia, whereas disease duration was less important in
      formation of SMI.

PMID- 21954635
TI  - [Structural and functional state of the left and right ventricle and the factors
      that affect the parameters of intracardiac hemodynamics in patients with
      hypertension and chronic alcohol intoxication].
AB  - The parameters of endocardiac hemodynamics, heart rate variability, endothelial
      function and function of the external breathing (FEB) were studied. 67 patients
      with arterial hypertension (AH) at the stage II and with chronic alcohol
      intoxication (CAI) were observed. Method of correlation analysis allowed to
      determine the heart rate variability effect on the hemodynamics, endothelial
      function and respiratory systems in these patients. Patients with AH and CAI in
      comparison with those without the syndrome of CAI had dilatation of right
      ventricle (RV) and left auricle and aorta on a background of low (aged 24-44
      years) or unchanged (aged 45-59 years) total peripheral vascular resistance. It
      was accompanied by ventricular diastolic impairment on a relaxation type, more
      shown in RV at patients of middle age. There are signs of sympathicotonia,
      obstructive disorders of the FEB in patients with hypertension and CAI.

PMID- 21954637
TI  - [Structurally-functional status of heart of the tuberculosis in teenagers].
AB  - The patients divided into two groups: in 12 patients (13-16 years old) including
      into I group observed decrease of internal size of the left ventricle, in 8
      persons (17-18 year old) revealed the elevation of internal size of the cavity of
      the left ventricle. From the analysis of results of the observations it is seen
      that, in patients including into 1 group the thickness of the wall of the left
      ventricle is higher than the internal size of the ventricular cavity. This time,
      the main aim of hypertrophy is the compensation of the increase of 2R/T
      thickening the wall of the left ventricle and decrease of the internal size of
      the ventricular cavity happened. Above mentioned showed the disadaptive character
      of the remodelization. The analysis of obtained results showed that in patients
      including into II group the increase of internal size of the left ventricle
      (EDSV, ESS, EDV, ESV) and the thinness of walls 2R/T bring to considerable
      decreasing. So, in teenagers during tuberculosis the changings (decrease and
      increase) of the internal size of the left ventricle resulted with the
      disturbance of the geometrical mechanisms. The changes in the geometrical
      structure of the ventricles resulted in disturbance and diastolic dysfunction of
      haemodinamics.

PMID- 21954636
TI  - [Evaluation of the cardiovascular function in patients with chronic rheumatic
      heart disease in the practice of medical and social expertise].
AB  - Chronic rheumatic heart disease (HRHD) for a long time occupied a prominent
      position in the structure of the disability population in Ukraine. Aim of the
      study is to define clinical signs of cardiovascular function in patients with
      HRHD for disability evaluation in the practice of medical and social expertise.
      We examined 180 patients with HRHD aged 40-65 years. There were significant
      differences in patient groups, which allowed us to formulate clinical and
      functional diagnostic markers of dysfunction of circulation for the objective
      assessment of the limitations of their life, the definition of disability groups
      and the development of rehabilitation programs.

PMID- 21954638
TI  - [Modern principles of chemotherapy of metastatic breast cancer].
AB  - Treatment of patients with metastatic breast cancer is one of the most difficult
      problems of clinical oncology. Chemotherapy is one of the main methods of
      treatment of patients with metastatic breast cancer. Long experience of the
      world's cancer centers, advances in clinical oncology recent decades, the
      synthesis of anticancer drugs with new mechanisms of action have led to progress
      in the treatment of disseminated breast cancer. However, as shown by recent
      studies, the improvement of chemotherapy is not associated with reduced mortality
      from this disease. This paper presents the effectiveness of anticancer drugs and
      their combinations in the treatment of patients with metastatic breast cancer.
      Compliance with which, as it seems to us to produce superior results in treating
      this disease.

PMID- 21954639
TI  - [Mathematical modeling and forecasting the prevalence of eye diseases].
AB  - The author proposed a mathematical model which predicts the prevalence of eye
      diseases in the next 5-7 years, taking into account the statistics in the
      incidence and dynamics of the prevalence of certain ocular diseases. It enables
      the development of realistic prevention and treatment programs to be proposed.

PMID- 21954640
TI  - [Clinical description of effectiveness of pioglitazone in a complex therapy of
      patients with ischemic heart disease on background of metabolic syndrome].
AB  - The results suggest that addition of pioglitazone in a complex treatment therapy
      of patients with ischemic heart disease on background of metabolic syndrome was
      not associated with an increased ischemic heart disease (IHD) risk and improved
      the clinical course of IHD, increased effectiveness of standard therapy for
      patients with IHD and metabolic syndrome.

PMID- 21954641
TI  - [Efficacy of metformin as initial therapy in patients with coronary artery
      disease and diabetes type 2].
AB  - The use of metformin during the first month of treatment of patients with
      coronary artery disease and diabetes type 2 led to the decrease of insulin
      resistance and reduced activity of systemic inflammation (significant decrease in
      the concentrations of IL-1, IL-6, IL-8 and TNF-alpha). Reduced activity of
      systemic inflammation had a beneficial effect on the course of coronary artery
      disease (significant decrease in the functional class of stable angina). Type 2
      diabetes appears to be quite successfully modifiable risk factor for coronary
      artery disease by the adequate controls.

PMID- 21954642
TI  - [Cliniko-laboratory indicators of efficiency fermento-substitution therapy of
      Gaucher disease in Ukraine].
AB  - The analysis of efficiency of treatment of 17 patients with Gaucher disease (GD)
      in Ukraine who had received fermento-substitution therapy for 2 years and more
      was conducted on the basis of clinical and laboratory monitoring data. Regular
      infusions of recombinant glucocerebroside reduced signs of hepatosplenomegaly and
      pancytopenia, reduced a bone pain and a bone crisis at the majority of patients
      with GD I type that led to considerable improvement of health state and
      improvement of patients life quality. Efficiency of treatment depended on
      regularity of drug administration, dosage and severity level of the disease at
      the start of the therapy. Adult patients were not seen to have corrections of
      bones and neurologic disorders after the treatment that confirmed necessity of an
      early initiation of the treatment, before formation of irreversible changes in
      these organs and systems. Chitiotriodase activity in blood plasma is the most
      complex laboratory indicator which displays activity of pathological process in
      patients with GD, therefore it is necessary to use it for an estimation of
      treatment efficiency to correct a recombinant glucocerebroside dosage.

PMID- 21954643
TI  - [Dynamics of humoral antiendotoxin immunity in patients with unhospital pneumonia
      during therapy Bifi-form Kids].
AB  - The aim of the work was to study the total level of antiendotoxin antibodies in
      blood serum of children of early age with community-Acquired pneumonia (CAP),
      with intestines dysbacteriosis in dynamics of the disease, and correction of
      intestine dysbiotic changes using modified regimen of a probiotic Bifi-form Kids
      drug administration. In the course of the study we found that acute period of CAP
      had considerable changes of antiendotoxin immunity which declared clear increase
      in the level of anti-et-antibodies in blood and concentration of the last ones
      directly depended on severity of the disease. After probiotic Bifi-form Kids had
      been prescribed in a complex treatment of children with CAP, the level of anti-et
      antibodies considerably decreased in comparison with children who did not take
      this probiotic. After treatment with high dosages of the probiotic of children
      with severe CAP, the indicator of total anti-et-antibodies considerably decreased
      in comparison with the children who received Bifi-form Kids probiotic in a
      standard dosage. The obtained data testifies on necessity of inclusion in a
      complex treatment of probiotica in higher doses during severe course of the
      disease.

PMID- 21954644
TI  - [Clinical and bacteriological efficiency of two modes of ceftazidim and aminkacin
      dosing in patients with ventilator-associated pneumonia].
AB  - Clinical and bacteriological effectiveness of two regimes of dosages of
      ceftazidime and amikacine in patients with ventilator-associated pneumonia (VAP)
      was evaluated. Patients were divided into two groups. 1A group--19 patients
      recieving antibacterial treatment for VAP where we used combination of
      ceftazidime 2 g i.v. 3 times a day and amikacine 500 mg i.v. 2 times a day. 1B
      group--21 patients who have had a combination therapy of ceftazidime and
      amikacine in changed regimes of dosages. The loaded dose of ceftazidime bolus was
      2 g i.v., then permanent infusion 3g per day. The dose of amikacine was 15 mg/kg
      per day once a day. The use of cephalosporins of the III-d generation and
      aminoglycosides in the high dosage is one of the possible safe forms to increase
      the effectiveness of antibacterial therapy in the treatment of nosocominal
      infection in the condition of polyresistent flora.

PMID- 21954645
TI  - [Efficiency therapy with rituximab in patients with non-Hodgkin's lymphomas].
AB  - Management of non-Hodgkin's lymphomas (NHL) has been significantly changed during
      last 40 years from radiotherapy to modern polychemotherapy with application of
      monoclonal antibodies. A ten year experience of the treatment of patients with B
      cell NHL with rituximab application was accumulated in National Cancer Institute.
      The group of patients with NHL, who were treated in oncohematology department in
      the period from 2001 to 2010, was chosen for study of the efficacy of the
      treatment with rituximab. The immediate and distant results of the treatment were
      evaluated in this group of patients. The usage of the polychemotherapy with
      rituximab was highly efficient in the treatment of primary and relapsed patients
      with NHL. This group shows high rate of the immediate and distant results of
      treatment.

PMID- 21954646
TI  - [Antialcoholic properties of a subalin probiotic drug].
AB  - Efficiency of a subalin probiotic drug created on the basis of live microbic
      cultures was investigated, at acute alcoholic intoxication developed in
      experimental animals. It was shown that after one time administration of this
      drug to animals there was no considerable influence on activity of the main
      enzymes of ethanol metabolism--alcohol- and aldehyde dehydrogenase both in
      animals with an alcoholic intoxication and without. However subalin induced
      considerable changes in the quantitative maintenance of acetaldehyde in blood of
      animals with alcoholic intoxication, which concentration decreased almost in 20
      times.

PMID- 21954647
TI  - [Comparative study of performance of lower extremities blocks under
      ultrasonography and nerve stimulator guidance].
AB  - The aim of the study was to conduct a comparative analysis of regional anesthesia
      under neurostimulator, ultrasound guidance, and under combined guidance of the
      neurostimulator and ultrasound to ensure the safe and effective control of
      regional anesthesia with minimal discomfort for the patient. Ultrasound allows to
      gain significantly higher quality scores of local anesthesia than nerve
      stimulator control, to significantly reduce the number of needle extra
      insertions, needling cases, transposition, addition of general anesthesia, the
      number of unsuccessful blocks, reduce needle manipulation, significantly increase
      the occurrence of cases of complete blockade (sensitive and motor) on 30 min.,
      causes less discomfort for patients. The use of ultrasound does not exclude the
      use of nerve stimulator as an additional means of verification of correct needle
      placement, particularly in the early stages of mastering the technique. The
      research combined use of ultrasound and nerve stimulator significantly decrease
      unsuccessful blockade and transposition need for a needle during manipulation.
      However, the difference between some indicators of quality of regional anesthesia
      is statistically unreliable; it requires further randomized and double blind
      studies on large patient groups, for different blockages.

PMID- 21954648
TI  - [Indexes of local cellular immunity for patients with generalized periodontitis].
AB  - The author studied the state of cellular factors of the system of immunity at 148
      patients with generalized periodontitis. It was revealed, that the features of
      disorders of immune answer in paradontium tissue are connected with the function
      of neutrophilus, activated T-cellers inflammatory and cytotoxicus immune answers,
      and also with changes of induction markers of apoptosis (CD95), expression of
      molecules of intercellular adgesion (CD54) and synthesis of lactoferrin. These
      indexes have a differential-diagnostic value for determination of character of
      course of the disease and immunopathogenesis mechanisms of paradontium tissue
      damage.

PMID- 21954649
TI  - [The outstanding figure of domestic military and civil public health services].
AB  - The article presents data on the outstanding Soviet theorist and the organizer of
      Health Care, full member of Academy of Medical Science of the U.S.S.R., the Hero
      of Socialist Work, the colonel general of a health service E.I. Smirnov who has
      developed a lot on the theory and practice of civil and military public health
      services. Its contribution to communication between organizational forms of
      medical maintenance of armies and principles of military art, and also dependence
      of quality of medical aid to the population on the organizational structure of a
      treatment-and-prophylactic network were considered. E.I. Smirnova's personal role
      in improvement of organizational forms of medical maintenance of armies, theory
      and practice development of intermediate treatments with evacuation to
      destination, in the organization of antiepidemic maintenance of armies and
      development number of actual questions of modern military medicine are shown in
      the article.

PMID- 21954650
TI  - Hepatocellular carcinoma, a rapidly increasing public health problem: the Tulane
      experience 2003-2009.
AB  - The rising incidence of hepatocellular carcinoma (HCC) in the United States is of
      importance to all practitioners. Louisiana has one of the highest HCC related
      mortality rates in the United States. Our study reviews the experience with HCC
      at Tulane University Medical Center from 2003 to 2009 and compares our experience
      with the national experience. Our data shows that from 2003 to 2009, the number
      of new HCC cases seen at Tulane increased by 300%, paralleling reported national
      trends. Infection with the hepatitis C virus (HCV) leading to cirrhosis is the
      most common factor in the development of HCC. In addition, our data suggests that
      diabetes may play a role in the development of HCC. Our study confirms the rising
      incidence of HCC in Louisiana and provides strong support for the rapid
      implementation of statewide surveillance programs for the early detection of HCC
      in individuals at risk.

PMID- 21954651
TI  - Clostridium difficile hospitalizations in Louisiana: a 10 year review.
AB  - Clostridium difficile (CD) is a common cause of diarrhea in hospitalized patients
      and can cause more serious intestinal conditions such as pseudomembranous
      colitis, toxic megacolon, perforations of the colon, sepsis, and even death.
      Clostridium difficile associated disease (CDAD) is mainly a health care
      associated illness. Known risk factors for CDAD are antibiotics, gastrointestinal
      surgery/manipulation, long length of stay in health care settings, serious
      underlying illness, a compromised immune system, and advanced age (>65+). In 2004
      a new epidemic strain of CD was identified as causing hospital outbreaks in
      several states. This new strain is more virulent and is more resistant to
      fluoroquinolone antibiotics. The Healthcare Cost and Utilization Project (HCUP)
      analyzed hospitalization discharge rates of CDAD in the United States (US)
      between 1993 and 2005 and reported that hospital discharges for CDAD doubled
      between 2001 and 2005. This study was done to see if Louisiana had similar trends
      in CDAD rates compared to the rest of the nation. Discharge records from the
      Louisiana Hospital Inpatient Discharge Database (LAHIDD) were analyzed for CDAD
      rates between 1999 and 2008 and were compared to the HCUPnet national estimates
      in the US. Trend and variance analyses were performed to compare demographics
      within Louisiana and overall trends to the US. Our results show that Louisiana
      had similar trends of CDAD rates compared to the US over the past 10 years.
      Furthermore, Louisiana also had a doubling of CDAD rates from 2001 to 2005.

PMID- 21954652
TI  - The public health threat from Balamuthia mandrillaris in the southern United
      States.
AB  - Balamuthia mandrillaris, formerly known as leptomyxid ameba, is an opportunistic,
      free-living ameba, related to Acanthamoeba that can cause skin lesions and
      granulomatous amebic encephalitis in individuals with compromised or competent
      immune systems. In order to make recommendations for early diagnosis, management,
      and prevention of typically fatal Balamuthia amebic encephalitis (BAE), this
      review described and analyzed laboratory-confirmed US cases of BAE for any
      consistent behavioral, demographic, environmental, ethnic, iatrogenic,
      occupational, recreational, or regional exposure factors over the study period,
      1980-2010. The ages of all case-patients were stratified by age and gender and
      compared for statistically significant differences by two-tailed, unpaired t
      tests. Potential risk factors were also stratified by age and gender, described,
      and compared by proportions and rates. The results of this study demonstrated
      that BAE occurred sporadically in patients of all ages in both immunosuppressed
      and immunocompetent patients. In addition, BAE exhibited only a few consistent
      predisposing factors that included male gender, exposure in a southern tier US
      state, and Hispanic ethnicity. Clinicians should suspect BAE in refractory cases
      of meningoencephalitis initially managed as aseptic or bacterial infections,
      especially in patients predisposed to BAE; confirm the diagnosis by
      immunodiagnostics, brain or skin biopsies, and institute conventional and,
      possibly, experimental, antiprotozoal therapy immediately. Brain dead victims of
      BAE are not suitable organ donors and have transmitted fatal BAE to organ
      transplant recipients.

PMID- 21954653
TI  - Nursing practice of checking gastric residual volumes based on old dogmas:
      opportunity to improve patient care while decreasing health care costs.
AB  - It is a common practice to check gastric residual volumes (GRV) in tube-fed
      patients in order to reduce the risk of aspiration pneumonia. However, there is a
      paucity of scientific evidence to support this practice which consumes
      significant amounts of health care resources. We conducted a survey of the
      nursing practice of GRV checks in our hospital as part of a systems improvement
      project using a standardized questionnaire in a single hospital setting. The
      questionnaire included questions about the practice of checking GRV including
      what constituted "high" GRV and adherence to physician orders. We observed a wide
      variation in the responses of the practice of management of GRV. All the nurses
      in our hospital checked GRV, whether or not there were physician orders. Nurses'
      responses to "high GRV" varied from 100 mL to 200 mL at which point they would
      withold feedings. Some, but not all nurses, would report the "high GRV" and
      witholding of feedings to the physicians. The wide variation of gastric residual
      checks, including unnecessary checks and withholding feedings, observed above not
      only increased health care costs but also has the potential to impact patient
      outcomes. This calls for a standardized evidence based tube-feeding protocol to
      check GRV and should be an integral part of hospital policy. For the benefit of
      the readers, we present the GRV check protocol instituted in our hospital which,
      based on anecdotal reports, is resulting in decreased interruptions of feedings
      to our patients and reducing the nursing time consumed, thus potentially
      decreasing health care costs.

PMID- 21954654
TI  - Endotracheal tube size does not affect time to extubation in adult cardiac
      surgery.
AB  - Managed care over the last 20 years has brought considerable attention to the
      impact of clinical variables on time to extubation in adult cardiac surgery. One
      variable that has not yet been analyzed is the endotracheal tube (ETT) size. Our
      retrospective electronic database review was performed on adult subjects that had
      a primary, non-emergent cardiac surgery in the last four years. The records of
      936 patients were analyzed to find 193 patients meeting inclusion criteria. Due
      to the low number of 7.0 ETTs used in the study, this group was eliminated from
      analysis. The means for times to extubation for the two remaining groups were
      7:45 standard deviation (SD) 4:27 (hrs:min) and 7:30 SD 4:48 (hrs:min) for
      patients managed with 8.0 and 9.0 ETTs respectively, with no statistically
      significant differences between the tube sizes p=0.2389. Analysis of variance did
      not demonstrate a statistically significant impact with age (p=0.3199), gender
      (p=0.5394), body mass index (BMI) (p=0.4060), nor intravenous (IV) anesthetic
      adjuvants midazolam (p= 0.4815) or opiates (p=0.3617) used in the operating room
      (OR), but length of time on cardiopulmonary bypass did play a role (p=0.0274).
      These data suggest that the size of the ETT utilized during cardiovascular
      surgery in adult patients does not play a role in the length of time of
      postoperative ventilation.

PMID- 21954655
TI  - A non-coronary syndrome cause of elevated troponin.

PMID- 21954656
TI  - Colonic large cell neuroendocrine carcinoma obscured by an initial diagnosis of
      diverticulitis.
AB  - Large cell neuroendocrine carcinomas are rare and aggressive colorectal
      malignancies that have a dismal prognosis. We present the following case of a
      patient who presented with signs and symptoms of diverticulitis. After failure of
      medical management, surgical intervention revealed a poorly differentiated
      adenocarcinoma with a component of large cell neuroendocrine carcinoma.

PMID- 21954657
TI  - ECG of the month: large left ventricle, paradoxically split second heart sound,
      and a continuous murmur. Sinus bradycardia, left bundle block, and QRS voltage of
      left ventricular enlargement.

PMID- 21954659
TI  - Radiology case of the month: 11-year-old girl with intramuscular hemangioma.
      Intramuscular hemangioma within the right soleus muscle.

PMID- 21954658
TI  - A 57-year-old man with diabetes and a toe infection.
AB  - Foot infections are common complications in the diabetic population resulting in
      significant associated morbidity. Several risk factors predispose these
      individuals to foot infections including, but not limited to, sensory neuropathy,
      autonomic neuropathy, motor neuropathy, atherosclerotic disease, hyperglycemia,
      and immune dysfunction.5 Medical work-up and treatment of diabetic foot
      infections depends on the extent and severity of the infection. An organized and
      practical approach based on an understanding of the pathophysiology and
      microbiology is helpful in the evaluation and treatment of these infections. 2

PMID- 21954660
TI  - Conviction, conversation, and collaboration. Editor's preface.

PMID- 21954661
TI  - Facing pain: Dr. Hans Killian's photo book, Facies dolorosa.

PMID- 21954662
TI  - Dissecting the pamphlet literature of the Boston smallpox inoculation
      controversy.

PMID- 21954663
TI  - Vaccination, poetry, and an early-nineteenth-century physiology of the self.

PMID- 21954664
TI  - Bad girls and biopolitics: abortion, popular fiction, and population control.

PMID- 21954665
TI  - Technology knows best: the cultural work of hospital birth in 21st century film.

PMID- 21954666
TI  - Collaboration across the disciplines: an experiment in interdisciplinary
      pedagogy.

PMID- 21954667
TI  - The time that remains: organ donation, temporal duration, and Bildung in Kazuo
      Ishiguro's Never let me go.

PMID- 21954668
TI  - Of bodies, families, and communities: refiguring the 1918 influenza pandemic.

PMID- 21954669
TI  - A novel approach in discovering significant interactions from TCM patient
      prescription data.
AB  - The efficacy of a traditional Chinese medicine medication derives from the
      complex interactions of herbs or Chinese Materia Medica in a formula. The aim of
      this paper is to propose a new approach to systematically generate combinations
      of interacting herbs that might lead to good outcome. Our approach was tested on
      a data set of prescriptions for diabetic patients to verify the effectiveness of
      detected combinations of herbs. This approach is able to detect effective higher
      orders of herb-herb interactions with statistical validation. We present an
      exploratory analysis of clinical records using a pattern mining approach called
      Interaction Rules Mining.

PMID- 21954670
TI  - Study on intelligent syndrome differentiation in traditional Chinese medicine
      based on multiple information fusion methods.
AB  - Numerous researchers have taken the solid step forward towards the
      objectification research of Traditional Chinese Medicine (TCM) four diagnostic
      methods. However, it is deficient in studies on information fusion of the four
      diagnostic methods. We establish four-diagnosis syndrome differentiation model of
      TCM based on information fusion technology. The objective detection instruments
      of four-diagnostic method are applied to collect four-diagnosis objective
      information of 506 cases of clinical heart-system patients. Then multiple
      information fusion methods are adopted to establish recognition model of
      syndromes. The results of our experiments show that recognition rates of the six
      syndromes using multi-label learning is better than OCON artificial neural
      network and multiple support vector machine.

PMID- 21954671
TI  - MAPLSC: a novel multi-class classifier for medical diagnosis.
AB  - Analysis of clinical records contributes to the Traditional Chinese Medicine
      (TCM) experience expansion and techniques promotion. More than two diagnostic
      classes (diagnostic syndromes) in the clinical records raise a popular data
      mining problem: multi-value classification. In this paper, we propose a novel
      multi-class classifier, named Multiple Asymmetric Partial Least Squares
      Classifier (MAPLSC). MAPLSC attempts to be robust facing imbalanced data
      distribution in the multi-value classification. Elaborated comparisons with other
      seven state-of-the-art methods on two TCM clinical datasets and four public
      microarray datasets demonstrate MAPLSC's remarkable improvements.

PMID- 21954672
TI  - Microarray data classification by multi-information based gene scoring integrated
      with gene ontology.
AB  - Selecting informative genes is one of the most important issues for deciphering
      biological information hidden in gene expression data. However, due to the
      characteristics of microarray data with small samples and large number of genes,
      general feature selection methods that are not biologically relevant become
      questionable. In this paper, we propose a novel classification method for
      microarray data by integrating the multi-information based gene scoring method
      with biological information. Through experimental evaluation, our proposed method
      is shown to deliver good accuracy in classification and provide biologists with
      deeper insights into the relations between genes and gene function categories.

PMID- 21954673
TI  - Applications of Self-Organising Map (SOM) for prioritisation of endemic zones of
      filariasis in Andhra Pradesh, India.
AB  - Entomological and epidemiological data of Lymphatic Filariasis (LF) was collected
      from 120 villages of four districts of Andhra Pradesh, India. Self-Organising
      Maps (SOMs), data-mining techniques, was used to classify and prioritise the
      endemic zones of filariasis. The results show that, SOMs classified all the
      villages into three major clusters by considering the data of Microfilaria (MF)
      rate, infection, infectivity rate and Per Man Hour (PMH). By considering the
      patterns of cluster, appropriate decision can be drawn for each parameter that is
      responsible for disease transmission of filariasis. Hence, SOM will certainly be
      a suitable tool for management of filariasis. The detailed application of SOM is
      discussed in this paper.

PMID- 21954674
TI  - A heuristic for gene selection and visual prediction of sample type.
AB  - In this paper, we introduce a heuristic method for gene selection. We target this
      method, coupled with RadViz visualisation, to the visual prediction of tissue
      samples which may exist in normal and disease states. As a result of this
      coupling, the gene selection process, predictive model training and evaluation as
      well as the model's application for tissue sample prediction can all be
      intuitively visualised. Such integrated visual analytics enhance the insight
      provided by classical statistics and machine learning methods. The case study
      shows our proposed method is cost effective and achieves competitive performance
      when compared with several widely used techniques.

PMID- 21954675
TI  - Prediction of the disulphide bonding state of cysteines in proteins using
      conditional random fields.
AB  - The formation of disulphide bonds between cysteines plays a major role in protein
      folding, structure, function and evolution. Many computational approaches have
      been used to predict the disulphide bonding state ofcysteines. In our work, we
      developed a novel method based on Conditional Random Fields (CRFs) to predict the
      disulphide bonding state from protein primary sequence, predicted secondary
      structures and predicted relative solvent accessibilities (all-state
      information). Our experiments obtain 84% accuracy, 88% precision and 94% recall,
      using all-state information. However, our results show essentially identical
      results when using protein sequence and predicted relative solvent
      accessibilities in the absence of secondary structure.

PMID- 21954676
TI  - Current management of small bowel obstruction.
AB  - SBO is a common disease with multiple causes. The most significant advances over
      the past several years have involved, first, decision-making techniques to
      promptly and accurately identify patients who will require exploration, and,
      second, the increasing use of laparoscopic techniques. "Complete" bowel
      obstruction is becoming an outdated term, as treatment algorithms use predictive
      models and oral contrast challenges to select patients for operation without
      recourse to the notion of "complete obstruction." Laparoscopic techniques are
      gaining acceptance as a primary modality in the treatment of SBO. Appropriate
      patient selection is necessary for success, but successful laparoscopic SBO
      management can reduce postoperative pain, minimize hospital stay, and may lead to
      fewer adhesions, possibly preventing further adhesive SBO. Strangulation
      obstruction is the major cause of morbidity and mortality in SBO. Although
      unrecognized strangulation obstructions remain, their incidence is decreasing
      with the new protocols in development. Future efforts should focus on
      incorporating predictive models into management with the goal of eliminating
      unrecognized strangulation obstructions. Further refinement of the predictive
      models incorporating outcomes of oral contrast challenges and molecular biomarker
      data may allow surgeons to reach this goal. In addition, the benefit of the
      elimination of interpractitioner variability conferred by standardized protocols
      will in itself improve patient outcomes.

PMID- 21954677
TI  - Screening for colorectal cancer.
AB  - March is national colorectal cancer awareness month. It is estimated that as many
      as 60% of colorectal cancer deaths could be prevented if all men and women aged
      50 years or older were screened routinely. In 2000, Katie Couric's televised
      colonoscopy led to a 20% increase in screening colonoscopies across America, a
      stunning rise called the "Katie Couric Effect". This event demonstrated how
      celebrity endorsement affects health behavior. Currently, discussion is ongoing
      about the optimal strategy for CRC screening, particularly the costs of screening
      colonoscopy. The current CRC screening guidelines are summarized in Table 2.
      Debates over the optimum CRC screening test continue in the face of evidence that
      22 million Americans aged 50 to 75 years are not screened for CRC by any modality
      and 25,000 of those lives may have been saved if they had been screened for CRC.
      It is clear that improving screening rates and reducing disparities in
      underscreened communities and population subgroups could further reduce
      colorectal cancer morbidity and mortality. National Institutes of Health
      consensus identified the following priority areas to enhance the use and quality
      of colorectal cancer screening: Eliminate financial barriers to colorectal cancer
      screening and appropriate follow-up of positive results of colorectal cancer
      screening. Develop systems to ensure the high quality of colorectal cancer
      screening programs. Conduct studies to determine the comparative effectiveness of
      the various colorectal cancer screening methods in usual practice settings.
      Encouraging population adherence to screening tests and allowing patients to
      select the tests they prefer may do more good (as long as they choose something)
      than whatever procedure is chosen by the medical profession as the preferred
      test.

PMID- 21954678
TI  - Varicose vein: current management.
AB  - The continued advancement of RFA and EVLS technology should provide for an
      increased safety profile and lasting efficacy for treating the major saphenous
      veins. The challenge lies in determining what type of patient comorbidities and
      anatomic variability result in higher recurrences after endothermal varicose vein
      treatment so that one can modify the choice of treatment appropriately. Further
      standardization of the FS technique may allow for its wider use in treating
      truncal varicosities. The powered phlebectomy system seems to be suited for
      isolated branch varicosities, but the sequelae of pain and ecchymosis may prevent
      it from becoming a mainstream treatment with stab phlebectomy and sclerotherapy
      as alternatives.

PMID- 21954679
TI  - Geographic variation in health care and the affluence-poverty nexus.
AB  - Almost 50 years ago, John F. Kennedy told Yale's graduating class that "what is
      needed today is a new, difficult but essential confrontation with reality, for
      the great enemy of truth is very often not the lie-deliberate, contrived and
      dishonest-but the myth-persistent, persuasive and unrealistic." Today's myth is
      the belief that 30% of health care spending is due to supplier-induced demand and
      that this amount could be saved if high-spending regions could more closely
      resemble low-spending regions. The reality is that, while quality and efficiency
      remain important goals, the major factors driving geographic differences are
      related to income inequality. Yet, following the road map of the Dartmouth Atlas,
      the Affordable Care Act includes penalties for hospitals with excess preventable
      readmissions (which are mainly of the poor), incentive payments for providers in
      counties that have the lowest Medicare expenditures (where there tends to be less
      poverty), incentives for physicians and hospitals that attain new "efficiency
      standards" (ie, costs similar to the lowest), and a call for the Institute of
      Medicine to recommend additional incentive strategies based on geographic
      variation. This scenario iscoupled with a growing bureaucracy, following the
      blueprint laid out by Brennan and Berwick in the 1990s, but with no tangible
      measures to increase physician supply. Meaningful health care reform means
      accepting the reality that poverty and its cultural extensions are the major
      cause of geographic variation in health care utilization and a major source of
      escalating health care spending. And it means acknowledging Bertrand Russell's
      admonition that a high degree of income inequality is not compatible with
      political democracy, nor is it compatible with health care that this nation can
      afford. As solutions are sought both within and outside of the health care
      system, misunderstandings of how and why health care varies geographically cannot
      be allowed to deter these efforts, and the pervasive impact of poverty cannot be
      ignored.

PMID- 21954680
TI  - Endovascular approaches to arteriovenous fistula.
AB  - AVFs differ in their characteristics, natural history, and response to
      interventions. These differences need to be considered when planning treatment.
      Endovascular treatments have emerged as a mainstay of treatment of all types of
      AVMs. They can be used as definitive therapy for acquired arteriovenous
      malformation, in remote or high-risk locations, and in elderly or otherwise
      debilitated patients. Endovascular control is often helpful in open repair of
      acquired AVF. Endovascular techniques are essential in the management of
      congenital AVF and are the first line of interventional therapy. In these cases,
      repeated interventions are the rule, and careful imaging and planning is the key
      to success.

PMID- 21954681
TI  - Local and regional control in breast cancer: role of sentinel node biopsy.
AB  - The development and acceptance of the SLND has profoundly affected the management
      of breast cancer. SLND has supplanted ALND as a highly accurate and less-morbid
      axillary staging procedure in patients with clinically node-negative early-stage
      breast cancer. SLND alone is associated with less than 1% isolated axillary
      recurrence in patients with node-negative disease and provides excellent regional
      nodal control. Historically, ALND has been the recommended treatment for patients
      with SLN metastases. ALND was thought to offer prognostic information, prevent
      axillary local recurrence, and possibly render a small survival benefit. However,
      resection of nonsentinel nodes with metastases may not affect survival, and not
      all axillary metastases progress to become clinically evident. Furthermore, with
      increased understanding of tumor biology, nodal status and number of involved
      lymph nodes are no longer the only determinants of systemic therapy. As improved
      breast cancer screening allows identification of early-stage disease localized to
      the breast, and because treatment plans are more often made on the basis of tumor
      biology, the role of completion ALND may be less critical. The low LRR rates seen
      in the ACOSOG Z0011 trial, several other randomized trials, and retrospective
      reviews suggest that SLND alone may provide adequate locoregional control and
      provide adequate information to guide adjuvant systemic therapy in selected women
      with clinically node-negative early-stage breast cancer.

PMID- 21954682
TI  - Stem cells in acute liver failure.
AB  - Patients with acute liver failure are a particularly challenging group, with
      unique difficulties faced in treatment decisions. Life-saving therapy is
      available, but organ shortage, delays in transplantation, and complications in
      management result in a high mortality in this group of patients even after
      transplant. Any pharmacologic intervention that improved outcomes in this
      population of critically ill patients would be of great benefit. Based on
      available evidence, different scenarios of participation of HSCs in liver
      recovery are conceivable. Encouraging HSCs to differentiate into hepatocytes or
      supply paracrine and cellular level support to accelerate ongoing local repair
      mechanisms and assist a failing liver with inadequate mass and functional
      capacity might be directed to occur effectively in humans. Evidence within small
      animal models of liver injury and observations within the human population
      suggest that this might also be encouraged. The use of pharmacologic agents to
      mobilize hematopoietic stem cells is well established and effectively used in a
      different population of patients. As such, extending the use of these drugs, such
      as plerixafor, to the human population has a sound basis. However, there is a
      need for clarification of the mechanisms by which these cells exert their effect
      as well as which specific population of cells is involved in the regenerative
      process. To be clinically relevant in scenarios of acute liver failure, stem cell
      mobilizing strategies would have to impact survival when administered well after
      injury. Applications in other settings may also prove useful. Limits to liver
      resection exist where the size of the future liver remnant governs the extent of
      resection possible. Preexisting functional impairment may be restrictive, and
      strategies involving stem cells may assist the future liver remnant in both
      normal and functionally impaired livers. Benefit has already been reported from
      treatment with G-CSF in other injured tissues, including the injured myocardium
      and acutely injured kidney. However, as yet no clinical trial exists to assess
      the effects of stem cell mobilization in humans with acute liver failure. The
      familiarity in the use of and success demonstrated in the clinical and
      experimental use of plerixafor and G-CSF make exploration of hematopoietic stem
      cells as therapy in patients with acute liver failure appealing.

PMID- 21954683
TI  - Is there a role for bowel preparation and oral or parenteral antibiotics in
      infection control in contemporary colon surgery?
AB  - The numbers of unanswered questions are many. Can intraoperative application,
      such as topical antimicrobial use in pulsed lavage, reduce the microbial burden
      on the wound interface before closure? Can closed suction drains within the
      closed surgical incision reduce infection rates, especially in patients with a
      large body mass index? What is the role of delayed primary closure or secondary
      closure in the wound where obvious contamination has occurred, or in the
      circumstance of emergent colonic resection where considerable contamination is
      encountered from preexistent perforation? Should immediate negative-pressure
      wound dressings be applied in the open contaminated wound? These and many other
      questions still confront the surgeon in the challenge of the surgical wound in
      major colorectal surgery.

PMID- 21954684
TI  - Oral antibiotics to prevent surgical site infections following colon surgery.

PMID- 21954685
TI  - Pancreatic necrosectomy.

PMID- 21954686
TI  - The impact of health care reform on surgery.

PMID- 21954687
TI  - Glucose elevations and outcome in critically injured trauma patients.
AB  - Tight glucose control is associated with improved outcome among critically ill
      trauma patients. Further research is necessary, however, to better elucidate the
      etiology of this beneficial therapy. Additionally, future randomized trials on
      this important topic are warranted, as are investigations of emerging
      technologies that better facilitate tight glucose control in the ICU after
      trauma.

PMID- 21954689
TI  - Choledochoceles: are they choledochal cysts?
AB  - The classification of choledochoceles as a type of choledochal cyst stems from
      the 1959 article by Alonso-Lej and colleagues describing 94 choledochal cysts,
      only 4 of which were choledochoceles. Even then, Alonso-Lej questioned the
      propriety of including the choledochocele, stating it was unclear "as to whether
      or not it originates from the same etiologic factors [as other choledochal
      cysts]". In 1971, Trout and Longmire also questioned the validity of classifying
      choledochoceles as choledochal cysts, noting the anatomic position article and
      variant mucosa of the choledochocele. Wearn and Wiot, in an article titled
      "Choledochocele: not a form of choledochal cyst", cite the differences in
      clinical presentation, demographics, and histology as reasons why choledochoceles
      represent separate entities from choledochal cysts. Over the ensuing decades,
      numerous investigators have questioned the legitimacy of classifying
      choledochoceles as choledochal cysts. In our recent series (the only one to our
      knowledge directly comparing patients with choledochocele and other [type I, II,
      IV, and V] choledochal cysts), patients with choledochoceles differed from
      patients with choledochal cysts in their age, gender, presenting symptoms,
      history of previous cholecystectomy, pancreatobiliary ductal anatomy, management,
      and most importantly, propensity to developing biliary malignancy. Based on the
      available cases of choledochoceles found in the literature, combined with the
      recent series from our institution, we conclude that choledochoceles seem to be
      distinct entities from choledochal cysts.

PMID- 21954690
TI  - What does ulceration of a melanoma mean for prognosis?
AB  - Ulceration of a primary cutaneous melanoma is clearly associated with worse
      prognosis, although the underlying mechanisms are not well understood. Recent
      studies have shown that the presence of ulceration may predict response to
      adjuvant IFN in high-risk patients. As molecular pathways continue to be
      elucidated, it is possible that continued study of ulceration will provide
      insight into potential therapeutic strategies, or will predict response to novel
      targeted therapies. Future investigation into melanoma ulceration is warranted.

PMID- 21954688
TI  - Advances in the surgical management of gastrointestinal stromal tumor.
AB  - Imatinib mesylate has revolutionized the treatment of GIST. Dramatic changes in
      clinical practice have been observed in the past decade. Nonetheless, time has
      also revealed the limitations of treating GIST with a single agent alone, as
      resistance to imatinib has become a significant clinical dilemma. Surgical
      resection still remains the only chance for a cure. However, it is clear that
      GIST is a complex disease and requires effective integration of surgery and
      targeted therapy to reduce recurrence after resection of primary GIST or to
      prolong survival in metastatic disease. Recent studies have begun to delineate
      the feasibility of multimodal treatment of this disease. Knowledge gained thus
      far, along with ongoing and future investigations of GIST, will be extremely
      relevant to the potential use of molecular targeted therapy for other solid
      neoplasms.

PMID- 21954691
TI  - Influence of surgical volume on operative failures for hyperparathyroidism.
AB  - Hyperparathyroidism is a disease that is often seen in the United States.
      Patients may present with a wide variety of symptoms affecting multiple organs,
      but frequently, they are found to be hyperparathyroid on a routine blood
      examination. Although these patients may be asymptomatic, new consensus
      guidelines exist for when they should undergo surgery, and several studies have
      shown multiple benefits from operative intervention. Surgical cure rates can be
      greater than 95%, but if the initial surgery is unsuccessful, the cure rate
      becomes 80%. In the hands of experienced surgeons, both initial cure rates and
      those for reoperations are much higher, illustrating that the surgical volume
      does affect failure in parathyroid surgery.

PMID- 21954692
TI  - Perioperative normothermia during major surgery: is it important?
AB  - PH caused by anesthesia-induced thermoregulatory inhibition and exposure to cold
      operating room environments still occurs in a significant proportion of patients
      undergoing major surgery. Although the association between specific perioperative
      temperatures (in and of themselves) and postoperative morbidity remains unclear,
      there is fair evidence to suggest that perioperative active warming may reduce
      the risk of postoperative cardiac events, bleeding, and SSIs. As such, proactive
      efforts by surgical teams to prevent PH are warranted and have become the
      standard of care at many institutions. Continued intraoperative monitoring of
      core temperature (ideally using esophageal probes) is recommended in all cases
      lasting more than 30 minutes, both to detect malignant hyperthermia and to
      maintain normothermia. Preoperative and/or intraoperative use of warmed forced
      air devices is an effective way to minimize redistribution hypothermia following
      induction, whereas intraoperative use of warmed i.v. fluids helps reduce the
      potential for fluid-induced hypothermia and, in turn, optimizes rates of
      perioperative normothermia.

PMID- 21954693
TI  - Surgical management of hereditary nonpolyposis colorectal cancer.
AB  - HNPCC is a diverse disease with significant colorectal and extracolonic
      malignancy risk. A high index of suspicion is necessary to identify patients and
      families who potentially have this disease. Patients suspected with Lynch
      syndrome should be referred for genetic counseling and testing for accurate
      diagnosis. Timely surveillance and intervention are essential to reduce the
      incidence and mortality from colorectal cancer. Once cancer is diagnosed,
      aggressive surgical management is warranted because there is significant
      metachronous colorectal neoplasia risk for all remaining colorectal mucosa. In
      medically fit patients, consideration should be given to colectomy for the
      treatment of colon cancer and proctocolectomy for the treatment of rectal cancer.
      For patients treated with anything less than total proctocolectomy, annual
      endoscopic surveillance of the remaining colorectum is mandatory.

PMID- 21954694
TI  - How to change general surgery residency training.

PMID- 21954695
TI  - Recent advances in the diagnosis and treatment of gastrointestinal carcinoids.

PMID- 21954696
TI  - The past, present, and future of biomarkers: a need for molecular beacons for the
      clinical management of pancreatic cancer.

PMID- 21954697
TI  - Robotic-assisted major pancreatic resection.
AB  - Robotic-assisted major pancreatic resections allow recreation of time-tested open
      surgical procedures on a minimally invasive platform. Early outcomes from robotic
      assisted major pancreatic resections are comparable with those of laparoscopic
      and open approaches. Robotic assistance has the potential to bring the well
      recognized advantages of minimally invasive surgery to major pancreatic
      resections. Technological innovations and increased surgeon familiarity with this
      approach will improve, likely leading to greater adoption and acceptance.

PMID- 21954698
TI  - Immunotherapy for metastatic solid cancers.
AB  - After decades of research on solid tumor immunology, immunotherapy has shown
      effectiveness in patients with metastatic solid cancers. Immune modulators such
      as IL-2 and anti-CTLA-4 can mediate tumor regression in patients with metastatic
      melanoma and renal cancer, two tumor types that appear exceptional in their
      ability to spontaneously harbor endogenous antitumor immune cells. The responses
      can be long lasting, but the number of patients who benefit from these molecules
      remains limited. Combinations of these agents with cytotoxic and biologic agents
      are being investigated as a means to increase response rates and in an attempt to
      broaden application to other cancer types. Rare responses to cancer vaccines
      suggest that a better understanding of the underlying biology and mechanism of
      actions may lead to wider application in the future. The most effective form of
      immunotherapy thus far, capable of eradicating large tumor burdens in melanoma
      patients, is the ACT of TIL given to patients after lymphodepletion. As an
      alternative, lymphocytes engineered to recognize tumor-associated antigens can be
      safely infused to patients. With this approach, tumor regression is now being
      reported for cancers other than melanoma, but success remains constrained by the
      identification of antigens expressed with high specificity by cancer cells and
      not by normal tissues.

PMID- 21954700
TI  - From the origin of sex-determining factors to the evolution of sex-determining
      systems.
AB  - Sex determination is typically classified as either genotypic or environmental.
      However, this dichotomy obscures the developmental origin and evolutionary
      modification of determinants of sex, and therefore hinders an understanding of
      the processes that generates diversity in sex-determining systems. Recent
      research on reptiles and fish emphasizes that sex determination is a
      multifactorial regulatory process that is best understood as a threshold
      dichotomy rather than as the result of genetically inherited triggers of
      development. Here we critically assess the relationship between the developmental
      origin of sex-determining factors and evolutionary transitions in sex-determining
      systems. Our perspective emphasizes the importance of both genetic and nongenetic
      causes in evolution of sex determination and may help to generate predictions
      with respect to the evolutionary patterns of sex-determining systems and the
      underlying diversity of developmental and genetic regulatory networks.

PMID- 21954699
TI  - Prophylaxis for deep vein thrombosis and pulmonary embolism in the surgical
      patient.

PMID- 21954701
TI  - It's all who you know: the evolution of socially cued anticipatory plasticity as
      a mating strategy.
AB  - Selection has led to the evolution of a variety of different mating strategies,
      each adapted to different competitive challenges. But what happens if the
      competitive challenges depend on the social environment? Here we discuss and
      review examples of socially cued anticipatory plasticity: irreversible
      developmental tactics in which resource allocation during the juvenile stage is
      altered to develop an appropriate phenotype for the competitive or mate choice
      environment that an individual encounters when mature. There are numerous
      theoretical and empirical examinations of the role of the social environment on
      the strength and direction of selection. However, only a handful of empirical
      studies examine how the social environment affects juvenile allocation and
      whether such tactics are adaptive. The goal of this review is to synthesize
      current knowledge about socially cued anticipatory plasticity, including the
      sensory modalities that individuals use to predict the adult competitive and
      mating environment. We then outline the various factors that are necessary for
      the evolution of socially cued anticipatory plasticity and discuss how this can
      affect phenotypic evolution. We conclude by suggesting some directions that
      future studies should take in order to understand how social variation can alter
      selection and the evolution of development.

PMID- 21954702
TI  - [Tissue and cell interactions in the oral mucosa after cytostatic drugs
      administration].
AB  - In the preceding work ("Morphology", 2011, issue 2), the regularities of oral
      mucosal (OM) epithelium injury after the cytostatic drug (CSD) treatment and its
      further regeneration, were reviewed. This paper presents the systematized summary
      of current literature data and the authors' own findings on the regularities of
      CSD effect on non-epithelial OM cell populations and their interactions with each
      other and the epithelium. The changes of intraepithelial tissue homeostasis,
      associated with CSD effect on intraepithelial lymphocytes, granulocytes,
      dendritic antigen presenting cells and melanocytes, interacting with
      epitheliocytes, are described. The data are presented, indicating that along with
      the epithelium, the cell populations of lamina propria and submucosal connective
      tissue, as well as the small blood vessels, are important targets of CSD in the
      OM tissues. The concept of a unifying model, describing tissue, cellular and
      molecular mechanisms of the oral mucositis development after CSD treatment, is
      reviewed.

PMID- 21954703
TI  - [Interconnections of the pallidum, pedunculopontine nucleus, zona incerta, and
      deep mesencephalic nucleus--the structures of the basal ganglia morpho-functional
      system].
AB  - Method of anterograde and retrograde axonal transport of horseradish peroxidase
      was used to study the organization of projections of different substructures of
      zona incerta (ZI), pedunculopontine nucleus (PPN), deep mesencephalic nucleus
      (DMN) complex, and functionally distinct structures of the pallidum of dog brain
      (n=20). It was found that pallidum and nucleus entope-duncularis are connected by
      reciprocal projections with dorsal, ventral and caudal sectors of ZI, as well as
      with DMN, lateral segment of the pars dissipata, and the pars compacta of PPN.
      The rostral sector of ZI, cuneiform and subcuneiform nuclei of DMN complex, the
      medial region of PPN pars dissipata are connected by ipsilateral projections with
      the same pallidal nuclei. Among all the structures studied, the presence of
      reciprocal connections with the ventral pallidum was found only in the lateral
      segment of the pars dissipata and pars compacta of PPN. The possible pathways of
      transfer of functionally different information and its integration in the
      investigated projection systems, are discussed.

PMID- 21954704
TI  - [Kainate receptors in the hippocampus of rat strains with different levels of the
      nervous system excitability].
AB  - Glutamate receptors in the central nervous system play a significant role in the
      mechanisms of differential adaptation to the environmental conditions. However,
      structural and functional parameters of kainate receptors (KR) under normal
      conditions and during exposure to stress are not well characterized. Therefore,
      the aim of this research was to 1) study the distribution and the quantity of KR
      GluR 5/6/7 subunits; 2) examine their changes in the pyramidal cell layer of the
      hippocampus in rat strains with have genetically determined distinctions in the
      levels of nervous system excitability following the exposure to short-term
      emotional-painful stress; 3) estimate the sensitivity of hippocampal pyramidal
      neurons to the action of KR agonist -kainic acid. It was demonstrated that GluR
      5/6/7 KR are localized mainly in the region of hippocampal CA2 area; in the
      animals with low excitability their quantity was greater than in those with high
      excitability. Short-term emotional-painful stress resulted in the increase of KR
      in hippocampal CA2 area only in highly excitable rats. Selective sensitivity of
      pyramidal neurons in different hippocampal fields to the action of kainic acid
      was demonstrated and it was found to depend on animal strain characteristics of
      of the nervous system excitability.

PMID- 21954705
TI  - [Ultrastructure of Mauthner neurons after optokinetic stimulation and eye
      enucleation].
AB  - It was previously shown that the contralateral (relative to preferred side of
      turns) optokinetic stimulation and ipsilateral eye enucleation cause a
      significant, 2- to 4-fold reduction of the ventral dendrite (VD) volume in one of
      two goldfish Mauthner neurons (MN) that becomes more active functionally. In this
      study, we investigated the MN ultrastructure after mentioned unilateral visual
      effects. In both cases, devastation of the afferent synapses was detected along
      the full length of the reduced VD, with simultaneous compaction of its
      cytoskeleton, in contrast to those of VD of the contralateral MN and of lateral
      dendrites and cell bodies of both neurons. It is suggested that the depleted
      synapses belong to the excitatory visual afferent input, and both cytoskeletal
      and synaptic mechanisms are involved in the regulation of MN functional activity
      through VD.

PMID- 21954706
TI  - [Structural changes in the neurons of the spinal nerve sensory ganglia of adult
      dogs during shin lengthening].
AB  - Using the Ilizarov apparatus, the shin of 9 adult mongrel dogs was lengthened.
      Morpho-functional state of the neurons in LVII spinal nerve sensory ganglia that
      are involved in tibial innervation, were studied using neurohistological and
      quantitative methods after the distraction that was performed during 28 days with
      the rate of 1 mm (4 fractions) a day, followed by one month-long fixation and one
      month after apparatus removal. Material, obtained 3 intact dogs was used as a
      control. The most intensive development of structural changes in different
      populations of sensory neurons was detected during the period of distraction;
      they persisted for one month after apparatus removal. As compared with the intact
      animals, in the populations of large, medium and small neurons, a 2-3 fold
      reduction was found in the number of normochromal cells with the central location
      of the nucleus and nucleolus in the center, with the concomitant proportional
      increase of the number of cells with the combined peripheral chromatolisis and
      dislocation of nuclear-nucleolar apparatus.

PMID- 21954707
TI  - [Changes the TRPV1-immunoreactive neurons of the rat spinal nerve sensory ganglia
      induced by capsaicin].
AB  - Morphological features of the TRPV1-immunoreactive neurons were studied in
      thoracic spinal nerve sensory ganglion in 10-, 20-, 30-, 60- and 90-day-old rats
      under normal conditions and after chemical deafferentation caused by capsaicin
      (100 mg/kg) subcutaneous injection at postnatal day 2. TRPV1-immunoreactive
      neurons differed in their morphometric characteristics: positive neurons had very
      small and small sizes, negative cells had the small, medium and large sizes.
      Capsaicin treatment of newborn rats was shown to change age dynamics of TRPV1
      positive neurons resulting in the reduction of the average cell cross-sectional
      area and cell numbers during the whole period of observation.

PMID- 21954708
TI  - [Early reactive changes of myelin sheath in the area of myelin sheath gaps (nodes
      of Ranvier) in nerve fibers (a supravital study)].
AB  - Using the inverted phase contrast microscope, the supravital study of structural
      dynamics of single myelin sheath gaps (nodes of Ranvier) of isolated frog myelin
      nerve fibers was performed after mechanical injury and in the medium with the
      decreased ion force under the conditions which induce, in electrophysiological
      experiments, the expression of the axolemmal K+-channels in the paranodal area.
      Videorecording has shown that within this area the myelin sheath stratification
      appeared that was associated with the swelling of Schwann cell cytoplasm enclosed
      in the terminal membranous loops of myelin. An increase of the degree of
      stratification of the lamellar myelin complexes make them invisible in the light
      microscope; therefore, it is not the translocation of the myelin sheath from the
      node cleft that is recorded, as many authors believed, but a shift of only the
      visible border of the compact, yet unstratified myelin sheath. Hence, the removal
      of myelin (demyelination) was absent, and the electrophysiological effect can be
      accounted for by a significant fall of electrical resistance in paranodal area as
      a result of swelling of terminal loops and stratification of the myelin sheath.
      Preparations examination also revealed a decrease of the axonal diameter in,
      which is proportional to swelling of the myelin sheath terminal parts. Since the
      outer fiber diameter did not change, it can be concluded that the process
      observed is the result of swelling of the Schwann cell cytoplasm due to the
      axoplasm water fraction which may be a peculiar process of axo-glial
      interactions.

PMID- 21954709
TI  - [Distribution and structural organization of autonomic neural apparatus of the
      rat pancreas (an immunohistochemical study)].
AB  - Using the immunohistochemical methods for detection of neurofilaments (NF),
      peripherin (PRF), synaptophysin (SF), tyrosine hydroxylase (TH) and Nissl
      staining with toluidine blue, thick sections (10-20 microm) prepared through all
      parts of pancreas of adult Wistar rats (n=7) were studied. The topography and the
      density of distribution of pancreatic islets in the various parts of pancreas
      were defined. The greatest density of the islets was found in the body of
      pancreas. The dense innervation of the organ was detected which included several
      nervous plexuses: the big-looped one consisting of nervous bundles and small
      trunks of NF-positive myelinated and unmyelinated nervous fibers, the second one
      was formed by PRF-positive thin posganglionic bundles of axons and microganglia,
      and the third one, detected with SF-staining, was main terminal plexus consisting
      of varicose axons with en passant synapses. Interactions of synaptophysin
      positive terminals (distant en passant synapses) with blood vessels, endocrine
      (islet) and exocrine cells, excretory ducts of the pancreatic lobules are
      described in details. Peculiarities of the structure of parasympathetic ganglia,
      their neurons, and pericellular synaptic apparatus are described; problems of the
      innervation and the nature of pancreatic insular endocrine cells are discussed.
      Attention is drawn to the fact that in no case neurons were found in the islets
      in the rat pancreas.

PMID- 21954710
TI  - [Probable sources of endothelial cells circulating in blood].
AB  - The aim of study was to determine the probable sources of circulating endothelial
      cells (CECs) and establish the role of both VE-cadherin and vascular endothelial
      growth factor (VEGF) in molecular mechanism of endothelium desquamation using the
      hemorrhagic fever with renal syndrome as the model of endothelium injury. Autopsy
      pieces of kidney, liver, lung, brain, stomach and myocardium taken from 10
      patients were studied histologically. Quantitative measurement of CECs was
      performed by the method developed by J. Hladovec (1978). Blood levels of VE
      cadherin and VEGF were determined by ELISA method. Predominant sources CECs were
      found to be macro- and microvessels of kidney, liver, lung, brain, gastric mucous
      membrane, myocardium and, possibly - brain vessels. One of the molecular
      mechanism of endothelium desquamation is VEGF-stimulated internalization of VE
      cadherin.

PMID- 21954711
TI  - [Morphodynamic analysis of lung microcirculation (a supravital morphological
      study)].
AB  - Using the system of contact optics, the circulation (microcirculation) was
      studied in the lungs of 15 adult Wistar rats during the normal physiological
      location of the organs inside the thorax. A 4x4 mm "window" was made in the
      tissues of the thorax of an anaesthetized rat, through which the pleura was
      incised, resulting in the lung collapse. The lung was filled with oxygen or
      hypoxic gas mixture under the pressure of 10-15 cm of water column through a
      tracheotomic cannula. Then the lung was brought in contact with the contact
      objective aperture (1.7 mm in diameter). Each alveolus was supposed earlier to be
      supplied with blood via a thinnest (5-10 microm in diameter) lung arteriole. The
      present study has shown that there exists a system of wide (20-30 microm in
      diameter and larger) microvessels, which run between the alveoli. These
      microvessels surround each alveolus, practically, from all the sides. In such a
      manner each alveolus is supplied by a maximal amount of blood. Such a structure
      of the lung circulation system accounts for a great blood flow through the lungs
      (up to 6 1 per minute in humans) and a rapid saturation of the blood with oxygen.

PMID- 21954712
TI  - [Age-related characteristics of melanocytes in the hair follicles of the temporal
      region skin in men].
AB  - Using morphometric and immunocytochemical methods, the distribution of melanin
      containing cells in the hair follicles was studied using the autopsy samples of
      the skin obtained from the temporal region of scalp of 74 male individuals of
      different age (10-79 years). In all age groups, the melanocytes were identified
      only in the epithelial hair matrix - both in sections stained with hematoxylin
      eosin and in sections treated with the monoclonal antibodies against tyrosinase.
      The examination of unstained sections demonstrated that after 15 years the
      reduction of a total area occupied by melanin granules in the cytoplasm of
      melanocytes and keratinocytes took place. After 26 years the irregular but stable
      decrease was found in the number of pigment-forming cells. The number of
      melanocytes identified using the monoclonal antibodies against tyrosinase, was
      greater then the number of pigment cell detected by routine methods.

PMID- 21954713
TI  - [Cellular composition of decidua basalis infiltrate during early pregnancy in
      urogenital mycoplasma infection].
AB  - The composition and distribution of immunocompetent cells in human decidua
      basalis at 6-8 weeks of pregnancy was studied immunonohistochemically under
      normal conditions (control group) and in infection with different mycoplasma
      species (microbial number> 104 CFU). In all the groups studied, monocytes were
      most numerous cells; large granular lymphocytes (phenotype: CD56++CD16-CD3),
      macrophages (CD68+) and immunonegative lymphocytes were observed in equal
      proportions; the least numerous populations were those of NK-cells (CD56+/
      CD16+), plasmocytes and granulocytes. No statistically significant differences
      were found between the content of these cells in all the investigated groups. The
      data obtained suggest that mycoplasma infection even characterized by high
      microbial number, does not cause significant changes in the composition of
      decidua basalis cellular infiltrate.

PMID- 21954714
TI  - [Astrocytes of the subventricular zone of the telencephalon].
AB  - Subventricular proliferative zone is the brain area most intriguing and least
      understood in terms of cellular and spatial organization. The objective of this
      study was to focus on the structural and cytochemical organization of astrocytes
      of the subventricular zone of the rat brain. Astrocytes were detected
      immunocytochemically. The preparations were analyzed using conventional light
      microscopy and confocal laser microscopy. The study performed showed that the
      major cellular population of the subventricular zone was represented by a special
      kind of atypical fibrous astrocytes with the intermediate filaments containing
      only glial fibrillary acidic protein (GFAP). The processes of these cells formed
      a complex double-layer network beneath the ependyma. The described structural
      pattern of the glial skeleton of the subventricular zone seems to be determined
      by specific functions of the area and its location in the zone of CSF-brain
      barrier.

PMID- 21954715
TI  - [The concept of the organ, as a hierarchal unit of human body, and its place in
      teaching histology at the medical university and medical college].
AB  - This paper deals with the methodological aspects of teaching histology at the
      medical university and medical college. The authors raise the issue of the
      necessity of teaching of the topic "Introduction to Special Histology" and the
      inclusion of the appropriate chapter into the textbooks. This is important for
      the students, as the formation of the general concepts of organ structure and
      function, components, and classification will aid in the further study of
      specific organs during the course of Special Histology. The authors describe
      their own experience in teaching of the section, dedicated to the general
      regularities of organ structure, present some definitions and classifications
      that are used by them for a number of years.

PMID- 21954716
TI  - [Interdisciplinary integration as an instrument for development a standard of
      medical education].
AB  - The formation of a competent doctor must be based on teaching standards for each
      discipline, the development of which is possible only as a result of provision of
      a real interdepartmental integration. The fundamental subjects must be taught not
      on the assumption of narrow professional interests, but in accordance with the
      requirements and demands of the clinical disciplines. The fulfillment of this
      task requires the development of a single computer base "Standards of Medical
      Education" and elaboration of the interdisciplinary modules. These must be based
      on the analysis of the "demand" of clinical Departments for new information
      blocks, the distribution of these blocks into different parts of the syllabus,
      their filling with the appropriate content, development of the adequate forms and
      methods of teaching.

PMID- 21954717
TI  - [Discovery of the neutrophil extracellular traps begins a new stage in the study
      of neutrophil morphogenesis and function].
AB  - The purpose of the present review was to analyze the accumulating evidence
      regarding recently discovered novel defense mechanism of neutrophils - capacity
      to form neutrophil extracellular traps (NETs). Contact with pathogenic microbes
      and/or exposure to proinflammatory cytokines trigger the respiratory burst in the
      neutrophils with a subsequent initiation of a cell death (NETosis) which differs
      from apoptosis and necrosis. NETs are formed by the fibrils of decondensed
      chromatin (DNA/ histones), released from the neutrophil, which is closely
      associated with the antimicrobial proteins of cytoplasmic granules. Due to its
      three-dimensional structure, NETs are capable of retaining the microorganisms
      (bacteria, fungi and protozoa), while high local concentration of the
      antimicrobial substances provides their killing. The review presents the evidence
      of a potential defensive role of NETs in infectious diseases, traumas and
      surgical operations, as well as during the early stage of a repair process.
      Considering the role played by neutrophils in the immune response orientation via
      pentraxin-3 (PTX3), including the switching to adaptive immunity, it is necessary
      to study the subsequent interaction of DNA/histone exrtacellular structures with
      the tissue microenvironment.

PMID- 21954718
TI  - Multi-decadal changes in tundra environments and ecosystems: the International
      Polar Year-Back to the Future Project (IPY-BTF).
AB  - Polar and alpine environments are changing rapidly due to increases in
      temperature, which are amplified in the Arctic, as well as changes in many local
      factors. The impacts on ecosystems and their function have potential consequences
      for local residents and the global community. Tundra areas are vast and diverse,
      and the knowledge of geographical variation in environmental and ecosystem change
      is limited to relatively few locations, or to remote sensing approaches that are
      limited mostly to the past few decades. The International Polar Year, IPY,
      provided a context, stimulus and timely opportunities for re-visiting old
      research sites and data sets to collate data on past changes, to pass knowledge
      from old to new generations of researchers and to document environmental
      characteristics of sites to facilitate detection and attribution of future
      changes. Consequently, the project "Retrospective and Prospective Vegetation
      Change in the Polar Regions: Back to the Future," BTF, was proposed and endorsed
      as an IPY activity (project #512). With national funding support, teams of
      researchers re-visited former sites and data sets throughout the Arctic and some
      alpine regions. These efforts have amounted to a gamut of "BTF" studies that are
      collectively geographically expansive and disciplinary diverse. A selection of
      these studies are introduced and presented in the current issue together with a
      brief synthesis of their findings.

PMID- 21954719
TI  - Past and present permafrost temperatures in the Abisko area: redrilling of
      boreholes.
AB  - Monitoring of permafrost has been ongoing since 1978 in the Abisko area,
      northernmost Sweden, when measurements of active layer thickness started. In
      1980, boreholes were drilled in three mires in the area to record permafrost
      temperatures. Recordings were made twice per year, and the last data were
      obtained in 2002. During the International Polar Year (2007-2008), new boreholes
      were drilled within the 'Back to the Future' (BTF) and 'Thermal State of
      Permafrost' (TSP) projects that enabled year-round temperature monitoring. Mean
      annual ground temperatures (MAGT) in the mires are close to 0 degrees C, ranging
      from -0.16 to -0.47 degrees C at 5 m depth. Data from the boreholes show
      increasing ground temperatures in the upper and lower part by 0.4 to 1 degree C
      between 1980 and 2002. At one mire, permafrost thickness has decreased from 15 m
      in 1980 to ca. 9 m in 2009, with an accelerating thawing trend during the last
      decade.

PMID- 21954720
TI  - Multi-decadal changes in snow characteristics in sub-Arctic Sweden.
AB  - A unique long term, 49-year record (divided into three time periods 1961-1976,
      1977-1992, and 1993-2009) of snow profile stratigraphy from the Swedish sub
      Arctic, was analyzed with a focus on changes in snow characteristics. The data
      set contained grain size, snow layer hardness, grain compactness, and snow layer
      dryness, observed every second week during the winter season. The results showed
      an increase in very hard snow layers, with harder snow in early winter and more
      moist snow during spring. There was a striking increase in the number of
      observations with very hard snow at ground level over time. More than twice as
      many occasions with hard snow at ground level were observed between 1993 and 2009
      compared to previous years, which may have a significant effect on plants and
      animals. The changes in snow characteristics are most likely a result of the
      increasing temperatures during the start and the end of the snow season.

PMID- 21954721
TI  - Current state of the Altai glaciers (Russia) and trends over the period of
      instrumental observations 1952-2008.
AB  - Results of research into climate and glacier dynamics in the Altai Mountains
      (Russia) over the period of instrumental observations (1952-2008) are presented
      in this article. About 1030 glaciers with a total area of 805 km2 and volume of
      42.5 km3 have been recorded in the Altai Region. The average summer air
      temperature in different regions of the Altai has increased during the study
      period from about 0.2 degrees C (Aktru) to 1.1 degrees C (Akkem). The annual
      atmospheric precipitation rate has also increased, by 8-10%. Since 1952, the
      glacier area in different regions of the Altai has decreased by 9-27%, and volume
      by 12-24%. By 2008, as a result of degradation, the total number of glaciers was
      953 with an area of 724 km2 and volume of 38 km3.

PMID- 21954722
TI  - Changes in tundra pond limnology: re-sampling Alaskan ponds after 40 years.
AB  - The arctic tundra ponds at the International Biological Program (IBP) site in
      Barrow, AK, were studied extensively in the 1970s; however, very little aquatic
      research has been conducted there for over three decades. Due to the rapid
      climate changes already occurring in northern Alaska, identifying any changes in
      the ponds' structure and function over the past 30-40 years can help identify any
      potential climate-related impacts. Current research on the IBP ponds has revealed
      significant changes in the physical, chemical, and biological characteristics of
      these ponds over time. These changes include increased water temperatures,
      increased water column nutrient concentrations, the presence of at least one new
      chironomid species, and increased macrophyte cover. However, we have also
      observed significant annual variation in many measured variables and caution that
      this variation must be taken into account when attempting to make statements
      about longer-term change. The Barrow IBP tundra ponds represent one of the very
      few locations in the Arctic where long-term data are available on freshwater
      ecosystem structure and function. Continued monitoring and protection of these
      invaluable sites is required to help understand the implications of climate
      change on freshwater ecosystems in the Arctic.

PMID- 21954723
TI  - Assessment of biological and environmental phenology at a landscape level from 30
      years of fixed-date repeat photography in northern Sweden.
AB  - A 30-year series (1978-2007) of photographic records were analysed to determine
      changes in lake ice cover, local (low elevation) and montane (high elevation)
      snow cover and phenological stages of mountain birch (Betula pubescens ssp.
      czerepanovii) at the Abisko Scientific Research Station, Sweden. In most cases,
      the photographic-derived data showed no significant difference in phenophase
      score from manually observed field records from the same period, demonstrating
      the accuracy and potential of using weekly repeat photography as a quicker,
      cheaper and more adaptable tool to remotely study phenology in both biological
      and physical systems. Overall, increases in ambient temperatures coupled with
      decreases in winter ice and snow cover, and earlier occurrence of birch foliage,
      signal a reduction in the length of winter, a shift towards earlier springs and
      an increase in the length of available growing season in the Swedish sub-arctic.

PMID- 21954724
TI  - Expansion of canopy-forming willows over the twentieth century on Herschel
      Island, Yukon Territory, Canada.
AB  - Canopy-forming shrubs are reported to be increasing at sites around the
      circumpolar Arctic. Our results indicate expansion in canopy cover and height of
      willows on Herschel Island located at 70 degrees north on the western Arctic
      coast of the Yukon Territory. We examined historic photographs, repeated
      vegetation surveys, and conducted monitoring of long-term plots and found
      evidence of increases of each of the dominant canopy-forming willow species
      (Salix richardsonii, Salix glauca and Salix pulchra), during the twentieth
      century. A simple model of patch initiation indicates that the majority of willow
      patches for each of these species became established between 1910 and 1960, with
      stem ages and maximum growth rates indicating that some patches could have
      established as late as the 1980s. Collectively, these results suggest that willow
      species are increasing in canopy cover and height on Herschel Island. We did not
      find evidence that expansion of willow patches is currently limited by herbivory,
      disease, or growing conditions.

PMID- 21954725
TI  - Plant and vegetation dynamics on Disko Island, west Greenland: snapshots
      separated by over 40 years.
AB  - We report on a revisit in 2009 to sites where vegetation was recorded in 1967 and
      1970 on Disko Island, West Greenland. Re-sampling of the same clones of the grass
      Phleum alpinum after 39 years showed complete stability in biometrics but
      dramatic earlier onset of various phenological stages that were not related to
      changes in population density. In a fell-field community, there was a net species
      loss, but in a herb-slope community, species losses balanced those that were
      gained. The type of species establishing and increasing in frequency and/or cover
      abundance at the fell-field site, particularly prostrate dwarf shrubs, indicates
      a possible start of a shift towards a heath, rather than a fell-field community.
      At the herb-slope site, those species that established or increased markedly in
      frequency and/or cover abundance indicate a change to drier conditions. This is
      confirmed both by the decrease in abundance of Alchemilla glomerulans and
      Epilobium hornemanii, and the drying of a nearby pond. The causes of these
      changes are unknown, although mean annual temperature has risen since 1984.

PMID- 21954726
TI  - Long-term effects of grazing and global warming on the composition and carrying
      capacity of graminoid marshes for moulting geese in east Greenland.
AB  - Greening of the Arctic due to climate warming may provide herbivores with richer
      food supplies, resulting in higher herbivore densities. In turn, this may cause
      changes in vegetation composition and ecosystem function. In 1982-1984, we
      studied the ecology of non-breeding moulting geese in Jameson Land, low Arctic
      East Greenland. By then, geese consumed most of the graminoid production in
      available moss fens, and it appeared that the geese had filled up the available
      habitat. In 2008, we revisited the area and found that the number of moulting
      geese and the temperature sum for June-July had tripled, while the above-ground
      biomass in a moss fen ungrazed by geese had more than doubled. In a goose-grazed
      fen, the overall plant composition was unchanged, but the frequency of graminoids
      had decreased and the area with dead vegetation and open spots had increased. We
      suggest that climate warming has lead to increased productivity, allowing for
      higher numbers of moulting geese. However, the reduction of vegetation cover by
      grazing may have longer term negative consequences for the number of geese the
      habitat can sustain.

PMID- 21954727
TI  - Flora and vegetation of Tasiilaq, formerly Angmagssalik, southeast Greenland: a
      comparison of data between around 1900 and 2007.
AB  - The changes in the vascular plant flora of Tasiilaq, low arctic southeast
      Greenland, between around 1900 and 2007 were studied by comparing the data from
      historical literature with those of the field observations performed between the
      late 1960s and 2007. Since 1900, the percentage of widely distributed arctic
      species distinctly decreased, whereas that of the low arctic species somewhat
      increased, and boreal species hardly increased. Vegetation monitoring revealed
      minor changes and showed that several thermophilous and xerophilous species
      increased between 1968/1969 and 2007, whereas some hygrophilous species
      decreased. Repeated vegetation mapping of a shallow pond revealed conspicuous
      changes suggesting increased evaporation/precipitation ratios associated with
      environmental warming up and decreasing snow accumulation in winter, in line with
      results of previous investigations. In spite of climate warming, expansion of the
      town and increasing human impact, flora and vegetation on the whole appeared
      rather stable during the last 40 years without invading species or introductions.

PMID- 21954728
TI  - Four decades of plant community change in the Alpine tundra of southwest Yukon,
      Canada.
AB  - Repeat measurements from long-term plots provide precise data for studying plant
      community change. In 2010, we visited a remote location in Yukon, Canada, where a
      detailed survey of alpine tundra communities was conducted in 1968. Plant
      community composition was resurveyed on the same four slopes using the same
      methods as the original study. Species richness and diversity increased
      significantly over the 42 years and non-metric multidimensional scaling indicated
      that community composition had also changed significantly. However, the direction
      and magnitude of change varied with aspect. Dominant species were not replaced or
      eliminated but, instead, declined in relative importance. Fine-scale changes in
      vegetation were evident from repeat photography and dendro-ecological analysis of
      erect shrubs, supporting the community-level analysis. The period of study
      corresponds to a mean annual temperature increase of 2 degrees C, suggesting that
      climate warming has influenced these changes.

PMID- 21954729
TI  - Changes in tree growth, biomass and vegetation over a 13-year period in the
      Swedish sub-Arctic.
AB  - This study was conducted in the Swedish subArctic, near Abisko, in order to
      assess the direction and scale of possible vegetation changes in the alpine-birch
      forest ecotone. We have re-surveyed shrub, tree and vegetation data at 549 plots
      grouped into 61 clusters. The plots were originally surveyed in 1997 and re
      surveyed in 2010. Our study is unique for the area as we have quantitatively
      estimated a 19% increase in tree biomass mainly within the existing birch forest.
      We also found significant increases in the cover of two vegetation types--"birch
      forest-heath with mosses" and "meadow with low herbs", while the cover of snowbed
      vegetation decreased significantly. The vegetation changes might be caused by
      climate, herbivory and past human impact but irrespective of the causes, the
      observed transition of the vegetation will have substantial effects on the
      mountain ecosystems.

PMID- 21954730
TI  - Tree and shrub expansion over the past 34 years at the tree-line near Abisko,
      Sweden.
AB  - Shrubs and trees are expected to expand in the sub-Arctic due to global warming.
      Our study was conducted in Abisko, sub-arctic Sweden. We recorded the change in
      coverage of shrub and tree species over a 32- to 34-year period, in three 50 x 50
      m plots; in the alpine-tree-line ecotone. The cover of shrubs and trees (<3.5 cm
      diameter at breast height) were estimated during 2009-2010 and compared with
      historical documentation from 1976 to 1977. Similarly, all tree stems (> or =3.5
      cm) were noted and positions determined. There has been a substantial increase of
      cover of shrubs and trees, particularly dwarf birch (Betula nana), and mountain
      birch (Betula pubescens ssp. czerepanovii), and an establishment of aspen
      (Populus tremula). The other species willows (Salix spp.), juniper (Juniperus
      communis), and rowan (Sorbus aucuparia) revealed inconsistent changes among the
      plots. Although this study was unable to identify the causes for the change in
      shrubs and small trees, they are consistent with anticipated changes due to
      climate change and reduced herbivory.

PMID- 21954731
TI  - Forecasting alpine vegetation change using repeat sampling and a novel modeling
      approach.
AB  - Global change affects alpine ecosystems by, among many effects, by altering plant
      distributions and community composition. However, forecasting alpine vegetation
      change is challenged by a scarcity of studies observing change in fixed plots
      spanning decadal-time scales. We present in this article a probabilistic modeling
      approach that forecasts vegetation change on Niwot Ridge, CO using plant
      abundance data collected from marked plots established in 1971 and resampled in
      1991 and 2001. Assuming future change can be inferred from past change, we
      extrapolate change for 100 years from 1971 and correlate trends for each plant
      community with time series environmental data (1971-2001). Models predict a
      decreased extent of Snowbed vegetation and an increased extent of Shrub Tundra by
      2071. Mean annual maximum temperature and nitrogen deposition were the primary a
      posteriori correlates of plant community change. This modeling effort is useful
      for generating hypotheses of future vegetation change that can be tested with
      future sampling efforts.

PMID- 21954732
TI  - Multi-decadal changes in tundra environments and ecosystems: synthesis of the
      International Polar Year-Back to the Future project (IPY-BTF).
AB  - Understanding the responses of tundra systems to global change has global
      implications. Most tundra regions lack sustained environmental monitoring and one
      of the only ways to document multi-decadal change is to resample historic
      research sites. The International Polar Year (IPY) provided a unique opportunity
      for such research through the Back to the Future (BTF) project (IPY project
      #512). This article synthesizes the results from 13 papers within this Ambio
      Special Issue. Abiotic changes include glacial recession in the Altai Mountains,
      Russia; increased snow depth and hardness, permafrost warming, and increased
      growing season length in sub-arctic Sweden; drying of ponds in Greenland;
      increased nutrient availability in Alaskan tundra ponds, and warming at most
      locations studied. Biotic changes ranged from relatively minor plant community
      change at two sites in Greenland to moderate change in the Yukon, and to dramatic
      increases in shrub and tree density on Herschel Island, and in subarctic Sweden.
      The population of geese tripled at one site in northeast Greenland where biomass
      in non-grazed plots doubled. A model parameterized using results from a BTF study
      forecasts substantial declines in all snowbeds and increases in shrub tundra on
      Niwot Ridge, Colorado over the next century. In general, results support and
      provide improved capacities for validating experimental manipulation, remote
      sensing, and modeling studies.

PMID- 21954733
TI  - The relationship between organisational communication and perception.
AB  - Both researchers and managers search for the most appropriate form of
      organisational communication. The aim of such an organisational communication is
      to influence the receivers' perception to confirm, adapt or change behaviour
      according to the sender's intention. This paper argues that to influence the
      receivers' perception, a specific form of communication that is embedded in a
      specific organisational culture is required. It also demands prior knowledge of
      the existing organisational schemata and the current perception concerning the
      topic that has to be communicated. The rationale is that three obstacles hinder
      the objectives of traditional communication strategies to influence perception
      according to the sender's objectives. The first challenge is that a receiver of a
      certain message never garners one single, clearly pronounced message conveyed by
      one single person. Yet, few studies are based on multiple messages from various
      sources. This makes most of the communication strategies in use obsolete. The
      second strain is the dual mode of thinking that forms organisational members'
      perceptions: the heuristic and the cogitative (Taleb, 2010). Most organisational
      communication theories are based on the paradigm in which receivers of
      information process this information in a rational way, while research in the
      field of neurobiology (Lehrer, 2009) indicates that rationality is dominated by
      emotions. The third difficulty is that organisational members constrain to well
      established, ingrained schemas (Labianca et al., 2000; Balogun and Johnson,
      2004). Based on these existing schemas, the scattered information from multiple
      sources, and the inability to process that information through cognitive
      reasoning, organisational members construct perceptions that are not in line with
      the objectives of the sender's communication. This article reviews different
      communication theories, points out key concepts in the literature on individual
      and collective perceptions, and suggests directions to further research.

PMID- 21954734
TI  - Neither shall you desire your neighbour's endoscopic procedures.

PMID- 21954735
TI  - Breast metastases from lung carcinomas: a report of three cases.
AB  - Tumours metastasising to the breast are very infrequent, with an incidence of 0.4
      6.6% of all breast tumours. Occasionally a breast mass is the first indicator of
      a tumour arising elsewhere. Development of metastases to the breast from a lung
      cancer is very rare and the prognosis for such patients is poor. We present three
      patients who had metastases to the breast presenting clinically as the primary
      origin. It is important to distinguish a primary breast cancer from a metastasis,
      as different therapies are offered with considerably different outcomes.

PMID- 21954737
TI  - Is C-reactive protein helpful for early diagnosis of acute appendicitis?
AB  - PURPOSE: Appendectomy is one of the most common surgical procedures all over the
      world. Although various laboratory tests and imaging studies are available to
      improve the accuracy of diagnosis, the rate of negative appendectomy is still
      about 15-30%. This study was designed to assess the diagnostic value of
      quantitative C-reactive protein (CRP) in patients suspected to acute
      appendicitis. MATERIALS AND METHODS: In a prospective study, blood samples of 102
      patients were collected before appendectomy. CRP was measured by
      immunoturbidimetry and the data were compared with the final histopathologic
      reports. Diagnostic accuracy of the CRP test was analyzed by ROC curve. RESULTS:
      In histopathology, 83 patients (81/4%) had acute appendicitis and 19 (18/6%) had
      normal appendices. Considering 14 mg/lit as the cut-off point, this test shows
      59% (95% CI, 48-69%) sensitivity and 68% (95% CI, 47-88%) specificity. The
      positive and negative predictive values were 89% (95% CI, 80-97%) and 27% (95%
      CI, 14-39%), respectively. CONCLUSIONS: The measurement of CRP levels is not an
      ideal diagnostic tool for ruling out or determination of acute appendicitis.

PMID- 21954736
TI  - Analysing the serum levels of tumour markers and primary tumour data in stage III
      melanoma patients in correlation to the extent of lymph node metastases--a
      prospective study in 231 patients.
AB  - BACKGROUND: Serum tumour markers correlate with biological tumour behaviour and
      prognosis of patients. We collected prospective data of melanoma patients in
      tumour stage III before radical lymph node dissection. MATERIALS AND METHODS:
      Between 2003 until 2007 we collected 231 tumour stage III patients and analysed
      the preoperative serum tumour markers S100 (S100 calcium binding protein), NSE
      (Neuron specific enolase, Enolase 2), Albumin, LDH (Lactate dehydrogenase) and
      CRP (C-reactive protein) and evaluated the correlation to clinical and
      pathological data. We divided patients into a group with only a positive sentinel
      lymph node (group 1; n = 109) and a second with further lymph node metastases
      (group 2; n = 122). RESULTS: Patients of group 2 had a significant higher T level
      (p < 0.0001) and Breslow index (p < 0.0001). Patients with a higher Breslow index
      had a higher S100 serum level (p = 0.021). Patients of group 2 displayed a
      significant higher level of serum S100. The serum level of CRP correlated with
      increasing number of lymph node metastases. CONCLUSIONS: A higher Breslow index
      in tumour stage III patients seems to have an influence on lymph node metastases
      and on S100 serum level. Patients with more than a positive sentinel lymph node
      do have a higher S100 level.

PMID- 21954738
TI  - Perioperative risk factors, morbidity, and outcome of 145 patients during
      phaeochromocytoma resection.
AB  - BACKGROUND: Phaeochromocytoma and paraganglioma resection carries a high
      perioperative risk. The aim of this study was to determine the risk factors for
      and frequency of perioperative morbidity and mortality during resection of these
      tumours. METHODS: Computerized surgical, medical, and histopathology records, as
      well as anaesthesia cards for 145 patients undergoing surgery for
      phaeochromocytoma resection between 1995 and 2009 were analysed retrospectively.
      Preoperative notes, adverse intraoperative events, and postoperative
      complications occurring in the 30 days following surgery were recorded.
      Preoperative phenoxybensamine and propranolol dose, age, sex, ASA score,
      catecholamine urinary level and profile, tumour weight, duration of surgery, and
      malignancy and presence of bilateral tumours were investigated to determine their
      contribution to major intraoperative haemodynamic events. Univariate comparisons
      were carried out using the student t-test. The Mann-Whitney test was also used to
      allow for deviation from normality. Logistic regression with backward removal of
      insignificant variables was used for multivariate analysis. Spearman test was
      used for correlation analysis. RESULTS: The only statistically significant factor
      that increased the probability of intraoperative haemodynamic variability was the
      duration of surgery (p = 0.025). The most common intraoperative event was
      transient hypertension, occurring in 59 (40.7%) patients. Sustained hypertension
      was registered in only 10 (6.9%) patients. No mortality, myocardial infarction,
      or cerebrovascular incidents were recorded. CONCLUSIONS: We found that the
      severity of perioperative haemodynamic changes significantly correlated with the
      duration of surgery. Our patients had low perioperative morbidity and no
      mortality.

PMID- 21954739
TI  - Percutaneous nephrolithotomy in hypertensive patients with different sizes of
      instruments.
AB  - OBJECTIVES: The risk of major complications, especially hemorrhage, is
      significantly elevated during surgery in hypertensive patients. To determine
      whether percutaneous nephrolithotomy (PCNL) can be safely performed in the
      hypertensive patients using different sized instruments. METHODS: We reviewed the
      records of 602 patients undergoing PCNL at our institution and identified 53 who
      were on antihypertensive therapy at the time of surgery. Patients were
      categorized into three groups according to size of devices used in surgery :
      those 24 F percutaneous tract with 22 F nephroscope (Group 1, n = 12 [22.7%]; 26
      F percutaneous tract with 24 F nephroscope (Group 2, n = 19 [35.8%]) and 30 F
      percutaneous tract with 26 F nephroscope (Group 3, n = 22 [41.5%]). We compared
      the groups with regard to baseline characteristics, intraoperative parameters,
      stone-free and complication rates, and the length of hospitalization. RESULTS:
      There were no differences between the three groups in age, gender, weight and
      stone laterality. Fluoroscopy time, access to the collecting system and mean
      operative time for per cm2 stone did not differ between the groups. Hemoglobin
      decrease, postoperative hospital stay and blood transfusion rate was higher in
      group 3. Stones were completely cleared in 83.3%, 84.2% and 81.3% of patients,
      which increased to 91.6%, 89.5%, and 90.1% with adjunctive therapy in the group
      1,2 and 3, respectively. CONCLUSIONS: PCNL with smaller devices is a safe and
      effective method in hypertensive patients. It has significantly a shorter
      hospital stay and less bleeding rates compared to classical PCNL.

PMID- 21954740
TI  - Sigmoido-gluteal fistula--a rare complication in clinically asymptomatic chronic
      diverticulitis.
AB  - Chronic colonic diverticulitis may be associated with typical complications such
      as local abscesses, stenosis, bleeding, intraperitoneal bowel perforations or
      fistulas to other organs. Most commonly, fistulas exist between the colon and the
      bladder; nevertheless, they may also extend to the small intestine, other areas
      of the colon, ureter, uterus, salpinx, vagina, abdominal wall, portal- and
      mesenterial venous system, pleura, urachus, biliary system and the hip. We report
      on a patient with chronic colonic diverticulitis having an unusual sigmoido
      gluteal fistula along the sacrum, the piriformis muscle and sciatic nerve. The
      patient presented with sciatic nerve symptoms and recurrent gluteal abscess
      formation, but no other clinical symptoms leading to an abdominal pathology.
      Initially, that fact caused an unsuccessful local treatment under the
      differential diagnosis of a local gluteal abscess for about a year. Finally, a
      sigmoid colon resection with end-to-end anastomosis and a proximal diverting
      stoma was performed. The colostomy was closed electively five months later
      without any complication.

PMID- 21954741
TI  - A Fournier's gangrene after transurethral resection of the prostate.
AB  - Fournier's gangrene is a rapidly progressive and potentially lethal disease that
      affects the perineum and mal genitalia. Predisposing factors included age,
      diabetes, alcoholism, malnutrition, and low socio-economic status. Herein, we
      present a 70-year-old patient who developed Fournier's gangrene following
      transurethral resection of the prostate. He had no predispositional factors to
      develop Fournier's gangrene.

PMID- 21954742
TI  - Spontaneous duodenal intramural haematoma imitating pancreatic pseudocyst.
AB  - Spontaneous intramural duodenal haematoma develops mostly as a complication of
      anticoagulation therapy. Other causes were reported only as case reports. CT
      diagnostics has some typical features in an intramural haematoma of the small
      bowel. This is especially hyperdensity of the bowel wall during the first 10 days
      from the onset of symptoms (30-80 HU), which could contribute to the
      differentiation from other infiltrative processes. These features are fully
      expressed only in a certain part of patients. We reported a 54 year-old female
      treated for epigastric pain. The patient's history, laboratory data,
      ultrasonography and CT findings resulted in a mistaken diagnosis of acute
      pancreatitis, necrosis of the pancreatic body with a subsequent development of
      pancreatic pseudocyst. The CT guided drainage was performed. The correct
      diagnosis was made one year later--surgical treatment was indicated for clinical
      signs of GI obstruction and CT findings of pseudocyst recurrence. During the
      operation, there was a finding of intramural haematoma in the duodenojejunal
      border. We performed an evacuation of the haematoma and gastroenteroanastomosis.

PMID- 21954743
TI  - Metaplastic carcinoma of the breast with high grade spindle cell component with
      osteoid formation--a rare case report.
AB  - Metaplastic carcinoma breast is rare entity with incidence of 0.02% of all breast
      malignancies. The ranges of age at diagnosis as well as clinical symptoms do not
      differ from that of conventional invasive ductal breast cancer. We are reporting
      a rare case diagnosed as metaplastic breast carcinoma on ultrasonography and
      confirmed histopathologically. The case merits presentation because of its
      rarity, low frequency of axillary metastasis and difficulty in interpreting the
      morphological features which correspond with prognosis.

PMID- 21954744
TI  - Aorto-iliac stent graft infection complicated by endotension and consequent
      rupture of the aneurysmal sac: a case report.
AB  - We present a case report of a bifurcated aorto-iliac stent graft infection two
      years after implantation. The initial procedure of implantation as well as the
      patient's recovery was uneventful. Two years later the patient presented with a
      growing aneurysmal sac without a detectable endoleak and consequent rupture.
      Instead of graft explantation, we left the graft in situ and performed thorough
      debridement and an omentoplasty, because of the poor condition of the patient. A
      Staphylococcus species grew out of the cultures of the aortic wall. The patient
      recovered well without persistent infection and is still doing well after 43
      months. This conservative approach might be an alternative in patients who are
      deemed to be at high risk for classic graft explantation and an extra-anatomic
      bypass or in situ bypass.

PMID- 21954745
TI  - Thoraco-abdominal wall reconstruction after surgical debulking of a giant
      retroperitoneal liposarcoma: a case report.
AB  - A case of a patient with a recurrent dedifferentiated retroperitoneal liposarcoma
      with extensive invasion of the thoraco-abdominal wall including the skin,
      requiring reconstructive surgery after debulking of the tumor is reported.

PMID- 21954746
TI  - A tennis ball and music as a patients solution for pulsatile tinnitus.
AB  - We present the case of a 74-year-old man with a pulsatile somatosound causing
      insomnia and day-time irritation. Given the lack of salvation after medical
      therapy the patient went in search for a solution and found it in a tennis ball
      and radio. In this case, the somatosound was due to an extracranial arteriovenous
      malformation, but the differential diagnosis of pulsatile somatosounds is quit
      extended, ranging form vascular disorders to tumoral processes. This makes these
      cases challenging for all caretakers.

PMID- 21954747
TI  - Persistent sciatic artery aneurysm: a case report.
AB  - In early embryologic development the sciatic artery provides the blood supply to
      the lower limb bud. When the femoral artery develops, the sciatic artery
      involutes. However, in rare cases, the sciatic artery persists. It can be
      visualised as a prolongation of the inferior gluteal artery (branch of the
      internal iliac artery) and it accompanies the sciatic nerve at the posterior side
      of the hip. We present the case of a 47-year old woman who consulted because of a
      numb right foot which presented colder and paler than the left foot. She also had
      a right painful calf, especially after exercise. Upon physical examination and
      doppler ultrasound there were no popliteal nor pedal artery pulses in the right
      leg. CT angiography showed bilateral persistent sciatic arteries with aneurysm
      formation and the presence of an embolus in the popliteal artery at the right
      side. Treatment involved thrombolysis of the popliteal occlusion, followed by
      intra-aneurysmatic stent placement and embolectomy of the popliteal artery and
      its distal branches. Postoperative clinical results were remarkably good and the
      patients symptoms dissolved. CONCLUSION: A persistent sciatic artery is a rare
      vascular anomaly. It is more prone to vasculopathies such as aneurysm formation.
      In cases of acute ischemia, correct diagnosis and treatment of this anomaly can
      avoid serious medical consequences.

PMID- 21954748
TI  - Basic kinematics and biomechanics of the patello-femoral joint. Part 1: The
      native patella.
AB  - The patello-femoral joint (PFJ) enhances our ability of knee flexion and
      extension and is assumed to have evolved through men's ability of having adopted
      a bipedal gait. This articulation between patella and femur is relatively complex
      and displays intricate biomechanical behaviour. Forces in the patello-femoral
      joint are a function of the quadriceps force, and the angle of flexion of the
      knee. They are highly dependent on the distance between the patello-femoral joint
      and the centre of gravity, which explains why different activities despite
      equivalence in tibio-femoral angle may exert wide variations in patello-femoral
      reaction forces and contact pressures. During normal daily activities the PFJ
      becomes exposed to force values between 0.5 to 9.7 x body weight, whilst sporting
      activities create force values that approach up to 20 x body weight. Those forces
      are considerable and it is therefore not surprising that the PFJ is particularly
      susceptible to degenerative disease especially if its mechanical equilibrium is
      disturbed through injury, muscle weakness and congenital or developmental
      abnormalities. The clinician must be aware of biomechanical and kinematic
      specifics, the high patellofemoral load values, small patellofemoral contact
      areas, and resultant high stress magnitudes when trying to remedy such
      abnormalities.

PMID- 21954749
TI  - Tibial pilon fractures: a review of incidence, diagnosis, treatment, and
      complications.
AB  - Tibial pilon fractures are challenging to treat, as they are typically intra
      articular and associated with extensive soft tissue damage. We briefly review the
      anatomy of the distal tibia, as well as the pathophysiology of pilon fractures.
      The treatment of tibial pilon fractures is still controversial in the literature,
      and we present some of the available options. Consideration is also given to peri
      operative complications, such as preoperative oedema and blistering and late
      postoperative traumatic arthritis. Finally, we propose a treatment algorithm
      (used in our institution), taking into account the level of associated soft
      tissue injuries. The use of a 2-phase treatment protocol is recommended; however,
      to date, no absolute treatment protocol exists for these injuries.

PMID- 21954750
TI  - Osteoporotic fracture treatment.
AB  - Orthopaedic surgeons frequently have to deal with osteoporotic fractures of the
      distal radius, hip and proximal humerus. Low bone mineral density is not only
      associated with an increased fracture risk but also with more fracture
      displacement and reduction loss. The specific problems and main treatment options
      for these fragility fractures are reviewed.

PMID- 21954751
TI  - Excision arthroplasty following shoulder replacement.
AB  - Excision arthroplasty of the shoulder is a rarely performed procedure used in
      cases where replacement of a failed arthroplasty is not feasible. We report four
      cases of excision arthroplasty following a shoulder replacement, one performed
      for infection and three for instability. Excision arthroplasty resulted in very
      poor function with pain improvement in only two cases.

PMID- 21954752
TI  - Results of open arthrolysis for elbow stiffness. A series of 22 cases.
AB  - Severe posttraumatic elbow stiffness represents a significant invalidity. Between
      1990 and 2005 two surgeons performed open elbow arthrolysis in 30 adult patients
      (6 women, 24 men, mean age 30.8 years). All cases resulted from severe initial
      trauma, which had occurred on average 15.5 months previously. Four patients had
      extrinsic and 18 had mixed contractures; 13 had heterotopic ossifications.
      Operative complications included two peroperative joint instabilities and 3
      transient nerve palsies. Seven elbows were remobilized under anaesthesia, one
      month after the arthrolysis. Twenty-two patients could be reviewed, on average 56
      months after the arthrolysis. Seventy seven percent of the patients were
      satisfied. At final follow-up, the average arc of flexion-extension was 95
      degrees +/- 15 degrees (average flexion 120 degrees +/- 13 degrees, average
      flexion contracture 31 degrees +/- 6 degrees), with a mean improvement of 51
      degrees relative to the preoperative range (p < 0.001). The average arc of
      forearm rotation at final follow-up was 151 degrees +/- 23 degrees, with a mean
      improvement of 41 degrees (p < 0.05). No patient suffered persistent weakness or
      instability. The average VAS was 5/10, the average MEPI score 76, with 6
      excellent, 6 good, 6 fair and 4 poor results, mainly because of persisting pain.
      The average DASH score was 31.6 and the average SF-36 was 66. Significant
      correlations were observed between VAS and DASH, MEPI and SF-36. This series
      demonstrates that open arthrolysis may restore acceptable elbow motion in young
      active patients presenting with elbow stiffness following major trauma. However,
      full restoration of motion is rare; only 18% of the patients regained the
      functional arcs of motion reported by Morrey, but the majority were satisfied,
      given their preoperative degree of elbow stiffness. The ultimate result from both
      the patient's and the surgeon's perspectives is strongly dependent on persisting
      pain, which was frequent in this series and influenced the DASH, MEPI and the SF
      36 scores. Arthrolysis did not address the issue, if pain was the chief
      complaint.

PMID- 21954753
TI  - Radius-only intramedullary nailing for both-bones diaphyseal forearm fractures in
      children.
AB  - Both-bones diaphyseal forearm fractures are common injuries in the paediatric age
      group and are potentially unstable. Both-bones intramedullary nailing for these
      fractures is a minimally invasive procedure that maintains alignment, and
      promotes rapid bony healing. Good results have also been shown with single-bone
      fixation. We report our experience in treating these common injuries with radius
      only intramedullary nailing in 29 children. The clinical notes and radiographs
      were reviewed retrospectively. There were 9 girls and 20 boys; the mean age at
      the time of operation was 9 years (range: 5 to 17 years). Closed reduction was
      achieved in 21 patients, while eight patients required open reduction. Mean
      duration of follow-up was 6.8 months (range: 4 to 12 months). All fractures
      achieved clinical and radiological union at 6-8 weeks. Radius-only intramedullary
      nailing is a sufficient and effective option in treating both bones paediatric
      forearm displaced unstable type AO 22-A3 fractures, with excellent functional
      outcome and union rates.

PMID- 21954754
TI  - One-stage treatment of developmental dysplasia of the hip in untreated children
      from two to five years old. A comparative study.
AB  - A total of 38 children (49 hips) were retrospectively investigated to assess the
      efficacy and safety of one-stage treatment of developmental dysplasia of the hip
      (DDH) in untreated children from two to five years of age. Our method consisted
      of open reduction, Salter innominate osteotomy, femoral shortening and derotation
      osteotomy. The patients were distributed into two groups according to the age at
      which they were operated: Group I included 19 patients aged < 3 years (24 hips)
      and Group II included 19 patients aged > or = 3 years (25 hips). Mean follow-up
      was 5.08 years for Group I and 5.76 years for group II. Clinical and radiological
      assessment at final followup showed that the outcome was not significantly
      different between the two groups. Furthermore, after this follow-up period, the
      rates of avascular necrosis were similar. Children with DDH between two and five
      years of age were treated successfully with one-stage treatment.

PMID- 21954755
TI  - Arthrodiastasis for late onset Perthes' disease using a simple frame and limited
      soft tissue release: early results.
AB  - Perthes' disease (Legg-Calve-Perthes' disease) is relatively common in childhood,
      affecting 0.8/100.000 children. Late onset Perthes' disease, older than 8 years
      of age, constitutes about 20% of cases and is known for its aggressive course and
      poor outcome with chronic hip pain and stiffness. Although containment of the
      head in the acetabulum is the usual treatment for early cases, its results in
      treating late-onset cases are universally poor, so that many authors conclude
      that there is an upper age limit for effectiveness of containment treatment. The
      emerging philosophy of hip distraction (arthrodiastasis) with release of
      contractured muscle groups around the hip may be a new concept for treatment of
      late onset Perthes' disease. Thirty children with late-onset Perthes' disease
      (age > 8 years) presenting to the orthopaedic department at Sporting Health
      Insurance Student Reference Hospital - Alexandria, Egypt, between December 2004
      till November 2008 were treated by hip arthrodiastasis using minimal soft tissue
      release and a simple Ilizarov construct. At the end of an average follow-up
      period of 3.6 years (range: 2-7 years, SD 13) there was an improvement in the
      range of movement, pain, and superior and lateral subluxation of the head, with a
      statistically significant difference between pre and post-operative values.
      Minimal soft tissue release and hip distraction can be regarded as a salvage
      procedure for late onset Perthes' disease with hip pain, at the stage of necrosis
      or fragmentation. Furthermore, this method did not result in any alteration in
      the joint anatomy, thus allowing the possibility for future surgery, if needed.

PMID- 21954756
TI  - Minimal-invasive posterior approach for total hip arthroplasty versus standard
      lateral approach.
AB  - In this prospective study we compared clinical and radiological results and
      rehabilitation progress of 64 patients who underwent total hip arthroplasty using
      the standard lateral approach with 64 patients operated with a minimal-invasive
      (MIS) posterior approach. The outcome of our study did not show any significant
      differences with regard to patient's safety such as complication rate and
      radiological assessment of the cup position. There was no difference in the
      duration of surgery, blood loss, hospital stay and postoperative leg length
      discrepancy. Rehabilitation milestones were achieved earlier by MIS patients and
      three and six months postoperatively, the Harris Hip Score of the MIS group was
      significantly higher.

PMID- 21954757
TI  - Proximal femoral anatomy in total hip arthroplasty. A tri-planar computed
      tomographic assessment.
AB  - The relationship between the tip of the Greater Trochanter (GT) and the centre of
      the Femoral Head (FH) is commonly used as reference point to align the femoral
      component during hip arthroplasty. We performed tri-planar computed tomography
      analysis of the proximal femoral anatomy in a series of 150 patients (n = 150) to
      accurately delineate this relationship. The mean location for the centre of the
      FH was 8.64 mm (95% confidence interval, 9.44-7.83) distal to the tip of the GT.
      The centre of the FH was found to be distal to the tip of the GT in 90.6% of
      cases. Hence we would suggest caution in using the tip of the GT as a reference
      point during total hip arthroplasty as it could be associated with an inadvertent
      intraoperative leg lengthening.

PMID- 21954758
TI  - Hip abductor re-attachment audited using a wire marker.
AB  - A braided wire suture marker was used to assess the integrity of abductor muscle
      repair following direct lateral approaches to the hip. The effect of a failed
      abductor repair on functional outcome was determined. Patients underwent total
      hip arthroplasty performed by a single surgeon using the direct lateral approach.
      Following hip abductor repair a braided wire suture marker was stitched into the
      lower end of the flap. Subsequent suture movement was measured using radiographs.
      Oxford hip scores were collected prospectively. Fifty six arthroplasties were
      performed with no complications. Eleven percent (n = 6) of the repairs detached
      and 89% (n = 50) of the repairs were either intact or showed only slight
      movement. No association was demonstrated between wire movement and pre
      operative, post-operative, or post-operative change in Oxford hip score. Abductor
      repair failure did not significantly impact on functional outcome. It is proposed
      that the wire marker provides a simple method of making a standard follow-up hip
      radiograph more informative.

PMID- 21954759
TI  - Evaluation of the posterior cruciate ligament in long standing cruciate retaining
      total knee arthroplasty.
AB  - We evaluated the status of the posterior cruciate ligament in 52 knees with a
      cruciate retaining total knee arthroplasty 11 years after the index surgery. The
      evaluation consisted of the Knee Society scores, clinical examination of antero
      posterior laxity using the Lachmann test and posterior drawer test. We also used
      the KT 1000 device, stress radiographs and MRI scan to corroborate this. Three
      knees were found to be lax clinically and had a posterior tibial shift on
      radiographs. The MRI scans were able to delineate the posterior cruciate ligament
      in 86% of the knees. Eleven years after surgery, clinical, radiological and MRI
      scans when assessed in combination demonstrated the presence of a stable
      posterior cruciate ligament in 94%.

PMID- 21954760
TI  - Arterial anatomy of the free vascularised corticoperiosteal graft from the medial
      femoral condyle.
AB  - The free vascularised corticoperiosteal flap from the medial femoral condyle, as
      described by Doi and Sakai, can be used for difficult non-unions. This flap is
      supplied by the Descending Genicular Artery (DGA) and the Superomedial Genicular
      Artery (SMA). In this anatomical study we describe the anatomy of these arteries.
      The DGA was dominant in 24 of 34 cases (70%). If the DGA was absent or too small,
      the SMA was sufficiently large for an adequate supply of the graft area. We
      concluded that of all the dissected specimens the arteries were sufficiently
      large and long enough to be suited for microsvascular anastomosis.

PMID- 21954761
TI  - Deep intramedullary infection in tibial lengthening over an intramedullary nail.
AB  - Tibial lengthening over an intramedullary (IM) device is associated with a risk
      of deep intramedullary infection; there is so far no guideline for decision
      making between early removal and delayed removal of the nail. Tibial lengthening
      over an intramedullary nail/Rush pin was performed in 118 limb segments (63
      patients) from 2004 to 2008 in our institution. Fifty five patients had bilateral
      tibial lengthening. Ninety nine of the 118 segments went on to healing without
      infection, while 13 segments developed superficial infection and 6 segments
      developed deep infection. Among 6 patients with deep infection, 4 patients
      underwent early removal of the nail when deep infection signs and symptoms
      occurred and 2 patients underwent delayed removal of the nail at 11 months. The 6
      segments with deep infection differed significantly with respect t to the callus
      pattern (p < 0.05) and density (p = 0.0001) from those without infection and with
      superficial infection. In this small sugroup, removal of the nail was delayed in
      two patients as there was visible callus bridging at more than one cortex, and
      deep infection subsided after local drainage.

PMID- 21954762
TI  - Percutaneous double metatarsal osteotomy for correction of severe hallux valgus
      deformity.
AB  - Double osteotomy of the first metatarsal is an option in treatment of severe
      hallux valgus deformity. Good short-term results have been reported with
      percutaneous surgery in hallux valgus with moderate deformity. We report short
      term results with percutaneous double osteotomy of the first metatarsal in severe
      deformities. This is a prospective study of 6 patients with severe hallux valgus
      deformity who were treated with percutaneous double osteotomy of the first
      metatarsal (proximal closing wedge and distal chevron osteotomy) in 2008. They
      were assessed preoperatively and one year and two years after surgery, with
      clinical and radiological AOFAS MTP-IP score. All patients were satisfied. The
      AOFAS score improved from 34 to 84. The postoperative radiological assessment
      showed significant improvement, compared with preoperative values of the
      intermetatarsal and hallux valgus angles. No complications were encountered. Post
      operative stiffness of the first MT joint was observed but resolved after
      physiotherapy. This preliminary study showed that correction of severe hallux
      valgus deformity by percutaneous double osteotomy can achieve good clinical and
      radiological results. A larger number of cases with a longer follow-up is needed
      to firmly demonstrate the advantages of this technique compared with classical
      open surgical techniques in the treatment of severe hallux valgus deformities.

PMID- 21954763
TI  - A 14-year longitudinal comparison study of two treatment methods in clubfoot:
      Ponseti versus traditional.
AB  - The optimal management of idiopathic clubfoot has changed over three decades.
      Recently there has been an enthusiastic embracing of the Ponseti technique with a
      move away from the traditional stretch and strap technique. The purpose of this
      14-year comparative prospective longitudinal study was to directly assess the
      differences in results between these two treatment methods. Over the period of
      this study there were 52,514 births in the local population and all newborns with
      clubfoot were referred directly to the paediatric orthopaedic surgeon. Patient
      demographics, the Harrold & Walker Classification, and associated risk factors
      for clubfoot were collected prospectively and analyzed. If conservative treatment
      failed to correct the deformity adequately, a radical subtalar release (RSR) was
      undertaken (the primary outcome measure of the study). There were 114 feet (80
      patients): 64 feet treated 'traditionally' and 50 feet with the Ponseti
      technique. Idiopathic clubfoot was present in 76.25% of patients. Mean time to
      RSR was 333 and 44.1 weeks for the traditional and Ponseti groups respectively.
      In the traditional group 65.6% (CI: 53.4 to 76.1%) of feet underwent RSR surgery
      compared to 25.5% (CI : 15.8 to 383%) in the Ponseti group. When idiopathic
      clubfoot alone was analysed, these rates reduce to 56.5% (CI: 423 to 69.8%) and
      15.8% (CI: 7.4 to 30.4%) respectively. The Relative Risk of requiring RSR in
      traditional compared to Ponseti groups was 2.58 (CI: 1.59 to 4.19) for all
      patients and 3.58 (CI: 1.65 to 7.78) for idiopathic clubfoot. Introduction of the
      Ponseti technique into our institution significantly reduced the need for RSR in
      fixed clubfoot.

PMID- 21954764
TI  - Progressive correction of severe spinal deformities with halo-gravity traction.
AB  - Treatment of rigid and severe spinal deformities is challenging and risky.
      Preoperative halo-gravity traction can be used to progressively reduce the
      deformity before spinal fusion. The aim of this study was to evaluate the
      effectiveness of halo-gravity traction for the correction of severe spinal
      deformities. Fifteen patients were reviewed retrospectively. Their mean age at
      the beginning of traction was 13.5 years. The mean duration of traction was 64
      days. The main curve in the coronal plane improved from +/- 95 degrees to +/- 67
      degrees, a gain of +/- 28 degrees (range 0 degrees-50 degrees) or +/- 30%. The
      curve in the sagittal plane improved from +/- 96 degrees to +/- 78 degrees, a
      gain of +/- 18 degrees (range 0 degrees-45 degrees) or +/- 19%. Other authors
      report gains up to 46% and 43%, respectively in the coronal and in the sagittal
      plane, but this might be due to different conditions, techniques, and
      evaluations. One patient with a pre-existing neurological deficit developed
      paraplegia. According to the literature congenital curves with associated
      kyphosis are exposed to paraplegia. Halo-gravity traction is effective and is
      usually tolerated better than other techniques of traction using the halo device.

PMID- 21954765
TI  - Myths and facts of spondylodiscitis: an analysis of 183 cases.
AB  - The authors conducted a retrospective study on 183 cases of spondylodiscitis,
      treated conservatively (44%) or surgically (56%) between November 1991 and June
      2006. The male/female ratio was 99/84, and the mean age 62.6 years. The mean
      follow-up period was 12 years (range 4-19). Interesting from a clinical
      viewpoint: temperature, white blood cell count, and CRP were sometimes normal,
      while pain varied from slight to unbearable. The commonest risk factor was
      diabetes mellitus, and the most frequent pathogen was Staphylococcus aureus.
      Methicillin resistant Staphylococcus aureus (MRSA) was found in 6 patients, and 3
      or 50% of these died, in sharp contrast with the overall mortality rate of 8.7%.
      A neurological deficit was seen in 43.7% of the patients; complete recovery
      occurred in 71% of the patients with a Frankel D stage, but in only 15.4 to 222%
      of those with a stage A, B or C.

PMID- 21954766
TI  - Injection of calcium phosphate cement in the percutaneous treatment of fractures
      of the lateral tibial plateau.

PMID- 21954767
TI  - Paper and dynamic hip screw surgery--a cheap and effective aid for hip fracture
      reduction.
AB  - The reduction of hip fractures prior to using dynamic hip screw devices can be
      challenging. The use of folded paper recreates an optimal angle of 135 degrees to
      assess adequacy of hip fracture reduction and to alert the surgeon as to the
      precise entry point of the guidewire in the lateral cortex of the femur.

PMID- 21954768
TI  - Reversal of tetraplegia in a patient with haematogenous cervical epidural
      abscess.
AB  - Pyogenic haematogenous cervical epidural abscess complicated by tetraplegia is an
      uncommon entity, but its clinical importance overshadows its rarity. Predisposing
      risk factors for spinal epidural abscess include diabetes, intravenous drug
      abuse, liver disease, renal failure, malignancy, HIV, infection elsewhere,
      rheumatoid conditions, trauma and a number of spinal interventions. Lack of
      recovery and death are much more frequent when complete paralysis exists since
      more than 24 to 48 hours. Most authors combine decompressive laminectomy and
      antibiotics. Anterior decompression and needle aspiration are rarely used, the
      former more specifically in case of anterior abscess formation. A high index of
      suspicion along with reliance on gadolinium-enhanced MRI is essential to diagnose
      the pathology and institute appropriate treatment on an individual basis. The
      authors report on a diabetic male patient who developed a cervical epidural
      abscess with tetraplegia after dental extraction. He was treated within six hours
      by one stage anterior/posterior decompression and fusion, with complete recovery.

PMID- 21954769
TI  - Bifocal disruption of the knee extensor apparatus ("floating patella") in a 72
      year-old patient.
AB  - We present the unusual case of a simultaneous ipsilateral rupture of the
      quadriceps tendon and the patellar ligament in a 72-year-old male patient. No
      predisposing factors were diagnosed. After surgical treatment, the patient healed
      with full function and full range of motion.

PMID- 21954770
TI  - Double Hill-Sachs lesion: a report of two cases.
AB  - Hill-Sachs lesions are common after anterior dislocation of the shoulder. We
      present two cases of uncommon double Hill-Sachs lesions composed of a typical
      Hill-Sachs lesion and an atypical extra compression fracture with a rim of normal
      cartilage in between. Both patients had two anterior shoulder dislocations before
      surgery. These case reports show that recurrent posttraumatic anterior
      glenohumeral dislocations can result in increased damage to the humeral
      cartilage.

PMID- 21954771
TI  - Osteochondral allograft transplantation after excision of femoral head giant cell
      tumour: a case report.
AB  - We report a case of Giant Cell Tumour of the femoral head in a 22-year-old man
      that was excised and reconstructed with an osteochondral allograft. After 3.5
      years follow-up, the graft had completely united and there were no signs of
      recurrence or resorption; the patient had an excellent functional outcome.
      Osteochondral allograft transplantation may provide a viable option for joint
      salvage after excision of a benign or locally aggressive tumour in the femoral
      head in selected cases.

PMID- 21954772
TI  - Introduction to protein purification.

PMID- 21954774
TI  - Gel filtration: size exclusion chromatography.

PMID- 21954773
TI  - Introduction to chromatography.

PMID- 21954775
TI  - Ion exchange chromatography.

PMID- 21954776
TI  - High-resolution reversed-phase chromatography of proteins.

PMID- 21954777
TI  - Hydrophobic interaction chromatography.

PMID- 21954778
TI  - Immobilized metal ion affinity chromatography.

PMID- 21954779
TI  - Covalent chromatography.

PMID- 21954780
TI  - Affinity chromatography.

PMID- 21954781
TI  - Affinity ligands from chemical combinatorial libraries.
AB  - The above discussion provides examples of how to utilize the possibilities
      arising from different scenarios, related to the level of information available,
      to identify low molecular weight organic molecule affinity ligands to target
      proteins. In Table 10.1 the different published results are summarized in terms
      of the structure of the ligand, the target protein, and a reference to the
      relevant publication. Common to all reported cases of small molecule affinity
      ligands is a considerably lower selectivity and affinity compared to natural
      protein ligands. This lower affinity has to be compensated with more thorough
      work in the optimization of binding and elution conditions to obtain significant
      recoveries and purification factors.

PMID- 21954782
TI  - Affinity ligands from biological combinatorial libraries.

PMID- 21954783
TI  - Membrane separations.

PMID- 21954784
TI  - Refolding of inclusion body proteins from E. coli.

PMID- 21954785
TI  - Purification of pegylated proteins.
AB  - Separation of PEGylated proteins is challenging because PEG itself is a
      relatively inert, neutral, hydrophilic polymer and the starting point for
      PEGylation is a pure protein. Thus, other than molecular weight and size,
      differences in the physicochemical properties typically used to fractionate
      proteins may be slight between different PEGylated forms of a protein. The usual
      properties of electrostatic charge and molecular weight (size) form the basis of
      the most commonly used separation techniques, particularly IEC, SEC, and
      ultrafiltration. The main effect of PEGylation on ion-exchange separations is to
      shield the electrostatic charges on the protein surface and to reduce the
      strength of interactions with higher PEG chain molecular weight or higher
      PEGylation extent. Thus, ion exchange can be used very effectively to separate on
      the basis of PEGylation extent for low extents, but as N increases, the
      effectiveness of separation rapidly diminishes. Separation of positional isomers
      is possible by RPC or ion exchange at analytical scale, but it is problematic at
      the preparative scale due to the small size of the differences in electrostatic
      interactions between isomers. PEGylation imparts significant changes in molecular
      weight with each chain added to a protein and there are corresponding increases
      in molecular size, so SEC and ultrafiltration (and dialysis) are effective
      methods for separating native and PEGylated proteins. However, the relative size
      difference between variants differing in PEGylation extent by one adduct reduces
      with N, so that efficient SEC separation between PEGylated species differing by
      one PEG chain is not likely to be economic at the preparative scale for N > 3.
      This holds true even for PEG proteins produced with large PEG polymers (Mr > or
      =20 kDa). For small PEG polymers (Mr = 2 kDa), only native and PEGylated species
      can be separated effectively. At the analytical scale, with proper calibration,
      SEC can provide valuable information on PEGylation extent. Membranes can be used
      to reduce the concentration of smaller molecular weight species by dialysis but
      cannot fully remove them, and an operational trade-off between purity and yield
      is required. Gel electrophoresis can confirm PEGylation reactions have proceeded
      and indicate the relative purity of products, but its use to confirm PEGylation
      extent requires further research. The main drawback of separations based solely
      upon molecular size is that they cannot differentiate between positional isomers.
      Capillary electrophoresis is an exception, quantitatively combining any or all of
      size, shape, conformational freedom, and small differences in protein surface
      properties to separate by both PEGylation extent and positional isomerism.
      Relative hydrophobicity is a useful property for analytical separations using
      RPC, but HIC, which is used routinely for production-scale purification of
      proteins, does not appear to be particularly useful for separation of PEGylated
      species.

PMID- 21954786
TI  - Electrophoresis in gels.

PMID- 21954787
TI  - Conventional isoelectric focusing. In gel slabs and capillaries and immobilized
      pH gradients.

PMID- 21954788
TI  - Two-dimensional electrophoresis in proteomics.

PMID- 21954789
TI  - Protein elution and blotting techniques.

PMID- 21954790
TI  - Capillary electrophoretic separations.

PMID- 21954791
TI  - High throughput screening techniques in protein purification.

PMID- 21954792
TI  - When technology fatigue kicks in, rely on experts to lead the way.

PMID- 21954793
TI  - Emerging roles in interventional radiology.

PMID- 21954794
TI  - What is your role in interventional radiology?

PMID- 21954795
TI  - Cognitive-behavioral therapy for insomnia.

PMID- 21954796
TI  - The case of the tingling toes.

PMID- 21954797
TI  - Eight substances added to national carcinogen list.

PMID- 21954798
TI  - Complex role in complex times. Programs take aim at helping nurse managers lead
      nurses.

PMID- 21954799
TI  - Giving a helping hand, gloves, masks, other donations to Joplin nurses.

PMID- 21954800
TI  - Making HIT meaningful for nursing and patients.

PMID- 21954801
TI  - 30-minute pressure cooker? ANA, nurses say multiple factors come into play with
      passing meds.

PMID- 21954802
TI  - Back-to-school tips for keeping your child's smile healthy!

PMID- 21954803
TI  - Do mosquitoes have teeth?

PMID- 21954804
TI  - Questions about providing dependent coverage for children until age 26.

PMID- 21954805
TI  - Ready to hire! Now what?

PMID- 21954806
TI  - Who determines the standard of care?

PMID- 21954807
TI  - Tips for caring for an aging parent: part one.

PMID- 21954808
TI  - Dental contracts 101: a crash course on contracting with dental plans.

PMID- 21954809
TI  - Understanding the adolescent patient: the gateway to oral health promotion.

PMID- 21954810
TI  - Bucco-lingual 'dimple' technique for removing full-crown and cast-metal
      restorations.
AB  - Many longitudinal studies of the longevity of full-crown and cast-metal
      restorations have been made. Dentists and dental team members marvel at the crown
      or bridge that has been in place and functioning for 30 or 40 years in a mature
      or elderly patient. Dental insurance company statistics and clinical records seem
      to indicate, however, that the average life span of a crown is closer to seven or
      eight years. How do you respond to the patient who asks, "Doctor, how long will
      this crown/bridge last?" Whatever your answer, it is realistic to expect that a
      newly inserted crown or fixed bridge will require replacement at some point in
      the patient's lifetime.

PMID- 21954811
TI  - Steppingstones to success: community outreach and the U-M School of Dentistry.

PMID- 21954812
TI  - [Pass the salt!].

PMID- 21954813
TI  - [Primary hyperaldosteronism].
AB  - After the age of 45 years more than 50% of the population will suffer from
      hypertension. The most common etiology is primary hypertension; however, in cases
      of severe or refractory hypertension, one should always look for secondary
      causes. Primary hyperaldosteronism will be the most common etiology. We will
      review the causes of hyperaldosteronism and discuss its diagnosis, algorithms and
      treatment.

PMID- 21954814
TI  - [Renal sympathetic denervation: perspective of a promising treatment for
      hypertension].
AB  - The crucial role of the sympathetic nervous system activity in the initiation and
      maintenance of hypertension was already in mind in the 1920s when surgical
      options were proposed to severely hypertensive patients. Despite constant
      evolution of pharmacological treatments, one estimates that 15-30% of
      hypertensive patients are still not well controlled and present resistant
      hypertension. The development of a new endovascular catheter used for selective
      sympathetic renal denervation by radiofrequency offers new perspectives of
      treatment. Encouraged by the recent results of the first clinical trials in a
      targeted population, this procedure could be used in some more indications in the
      future. However, long term morbidity and mortality of this technique are still
      not known.

PMID- 21954815
TI  - [Usefulness of BNP measurement for stratifying cardiovascular risk in
      hypertensive patients].
AB  - The production of brain natriuretic peptide (BNP) by ventricular cardiomyocytes
      is increased in patients with left ventricular hypertrophy (LVH). Increased
      plasma levels of BNP or of the inactive fragment NP-proBNP are associated with an
      increased cardiovascular risk. The measurement of plasma concentrations of these
      peptides may be useful for stratifying the cardiovascular risk of hypertensive
      patients, particularly if there is no electrocardiographic evidence for LVH.

PMID- 21954816
TI  - [Do endothelin receptors antagonists have a place in the treatment of arterial
      hypertension?].
AB  - The discovery in 1988 of endothelin, the most potent human endogenous
      vasoconstrictor, has opened the race to the discovery of a new weapon against
      arterial hypertension. The development of the endothelin receptors antagonists
      (ERAs) and the demonstration of their efficacy in preclinical models initially
      raised a wave of enthusiasm, which was however tempered due to their unfavorable
      side effect profile. In this article we will review the phases of the development
      ERAs, and their current and future place as therapeutic tool against arterial
      hypertension.

PMID- 21954817
TI  - [Angiotensin II receptor blockers (ARBs) and cancer: a reassuring balance].
AB  - The effects of drugs on new cancer and cancer-related death are a major concern.
      Recently, a meta-analysis raised the possibility that ARBs might have an adverse
      impact in this respect. This point of view was highly debated until the
      publication of two other meta-analyses which did not demonstrate any increased
      risk of new cancer occurrence as well as of cancer related-death with the use of
      ARBs in patients with hypertension, heart failure and/or nephropathy. This
      illustrates that the results of meta-analyses should be interpreted cautiously
      and critically in order to avoid biased conclusions. Overall the bulk of evidence
      today indicates that ARBs are not associated with an increased cancer risk.

PMID- 21954818
TI  - [Anticancer drugs under pressure].
AB  - Angiogenesis inhibitor drugs, targeting VEGF (vascular endothelial growth factor)
      are used increasingly in oncology for a wide range of advanced cancers
      (colorectal cancer, lung cancer, renal cell cancer,...). Generally, they are well
      tolerated but cardiovascular and renal side effects may appear. The most frequent
      complications are hypertension and proteinuria which, very often, remain
      asymptomatic. Therefore, they have to be searched for systematically before and
      during the treatment. Sometimes, anti-hypertensive medication is needed. We are
      just beginning to understand the pathophysiological mechanisms of antiangiogenic
      therapies. Only a multidisciplinary approach will improve our knowledge of those
      target agents and allow a better management of the cancer patient.

PMID- 21954819
TI  - [Lights on connections between humanitarian medicine and general medicine].
AB  - Humanitarian Medicine's practical experiences show the potential violence of the
      medicine's power over bodies everywhere. The inequality between assistance and
      people receiving benefits is comparable to the asymmetrical relationship between
      doctor and patient. Efforts have to be done in order to comprehend other
      possibilities of life's organization. The understanding of double subjectivities
      in the therapeutic relationship is a requirement for success, in any situation-
      as usual. Furthermore, the adverse effects of assistance remind us the primary
      principle not to harm. These admissions of failure urge to develop assessment
      reasoning, including all factors of influence on health (resources, policy...),
      and an approach which aims people to become self-sufficient.

PMID- 21954820
TI  - [Early detection of autism: a questionnaire for parents. Interview with Hilary
      Wood].

PMID- 21954821
TI  - [Fontaine, I will not drink your heavy water].

PMID- 21954822
TI  - [Return of the salt tax on sugar and chips].

PMID- 21954823
TI  - [Consent and sexuality].

PMID- 21954824
TI  - [Stem cells: the first self-red blood cell transfusion].

PMID- 21954825
TI  - [Mrs. O].

PMID- 21954829
TI  - Ecological speciation in dynamic landscapes.
AB  - Although verbal theories of speciation consider landscape changes, ecological
      speciation is usually modelled in a fixed geographical arrangement. Yet landscape
      changes occur, at different spatio-temporal scales, due to geological, climatic
      or ecological processes, and these changes result in repeated divisions and
      reconnections of populations. We examine the effect of such landscape dynamics on
      speciation. We use a stochastic, sexual population model with polygenic
      inheritance, embedded in a landscape dynamics model (allopatry-sympatry
      oscillations). We show that, under stabilizing selection, allopatry easily
      generates diversity, but species coexistence is evolutionarily unsustainable.
      Allopatry produces refuges whose persistence depends on the characteristic time
      scales of the landscape dynamics. Under disruptive selection, assuming that
      sympatric speciation is impossible due to Mendelian inheritance, allopatry is
      necessary for ecological differentiation. The completion of reproductive
      isolation, by reinforcement, then requires several sympatric phases. These
      results demonstrate that the succession of past, current and future geographical
      arrangements considerably influence the speciation process.

PMID- 21954830
TI  - Observations of multiscale, stress-induced changes of collagen orientation in
      tendon by polarized Raman spectroscopy.
AB  - Collagen is a versatile structural molecule in nature and is used as a building
      block in many highly organized tissues, such as bone, skin, and cornea. The
      functionality and performance of these tissues are controlled by their
      hierarchical organization ranging from the molecular up to macroscopic length
      scales. In the present study, polarized Raman microspectroscopic and imaging
      analyses were used to elucidate collagen fibril orientation at various levels of
      structure in native rat tail tendon under mechanical load. In situ humidity
      controlled uniaxial tensile tests have been performed concurrently with Raman
      confocal microscopy to evaluate strain-induced chemical and structural changes of
      collagen in tendon. The methodology is based on the sensitivity of specific Raman
      scattering bands (associated with distinct molecular vibrations, such as the
      amide I) to the orientation and the polarization direction of the incident laser
      light. Our results, based on the changing intensity of Raman lines as a function
      of orientation and polarization, support a model where the crimp and gap regions
      of collagen hierarchical structure are straightened at the tissue and molecular
      level, respectively. However, the lack of measurable changes in Raman peak
      positions throughout the whole range of strains investigated indicates that no
      significant changes of the collagen backbone occurs with tensing and suggests
      that deformation is rather redistributed through other levels of the hierarchical
      structure.

PMID- 21954831
TI  - Interleukin-6 autocrine signaling mediates melatonin MT(1/2)  receptor-induced
      STAT3 Tyr(705)  phosphorylation.
AB  - Melatonin receptors have previously been shown to elicit cellular signaling
      through the hematopoietic-specific G protein, G(16) . In the present study, we
      show that this functional coupling elicited biphasic stimulatory phosphorylation
      on STAT3 in recombinant MT(1) /Galpha(16) cells and native Jurkat T cells
      (endogenously expressing MT(1) and Galpha(16) ), with maximal Ser(727)
      phosphorylation occurring at 15min, while marked Tyr(705) phosphorylation became
      detectable only upon agonist treatment for 4 hr or more. By employing signal
      transducer and activator of transcription 3 (STAT3) phosphorylation-resistant
      mutants (STAT3-Y705F and STAT3-S727A), we further showed that the receptor
      mediated STAT3 phosphorylations at Ser(727) and Tyr(705) were independent of each
      other. Results obtained from fractionation of 2-IMT-induced cells revealed that
      the Ser(727) and Tyr(705) phosphorylations were spatially distinct, with the
      former mainly situated in mitochondria and cytosol, while the latter was
      predominantly located in the nucleus. Further experiments revealed that the
      agonist-induced STAT3 phosphorylation at Tyr(705) was significantly suppressed by
      pretreatment with cycloheximide (a ribosome inhibitor), suggesting that de novo
      protein synthesis might play a critical role for this response. Using conditioned
      media obtained from 2-IMT-treated MT(1) /Galpha(16) cells, multiplex immunoassays
      revealed that prolonged agonist treatment led to elevated productions of IL-6, GM
      CSF and CXCL-8. Antibody against IL-6, but not those for GM-CSF and CXCL-8,
      effectively abolished the agonist-induced STAT3 Tyr(705) phosphorylation,
      suggesting the involvement of IL-6 in melatonin receptor-mediated STAT3
      activation. Our results demonstrate that melatonin receptor/Galpha(16) coupling
      is capable of triggering the production of cytokines including IL-6, and this
      autocrine loop may account for the subsequent STAT3 phosphorylation at Tyr(705) .

PMID- 21954832
TI  - Image recognition with a limited number of pixels for visual prostheses design.
AB  - With the rapid development and crossover among the information science,
      microelectronics, material science, and biomedical disciplines, the visual
      prosthesis makes visual reparation possible. Because the number of stimulation
      electrodes is strictly limited by various complicated factors, it is necessary to
      determine the minimum visual requirements to achieve useful artificial vision for
      image recognition. This research has studied how many pixels individual images
      need to have to be correctly and economically recognized by blind subjects. In
      order to extract the figure of the image with a limited number of pixels, we have
      proposed a wavelet-based image processing methods, and six resolutions (8 * 8, 16
      * 16, 24 * 24, 32 * 32, 48 * 48, and 64 * 64) are investigated. Psychophysical
      experiments have been designed to verify our proposed image processing method and
      to investigate the recognition accuracy with a limited number of pixels. The
      results show that the recognition accuracy increases with the number of pixels.
      The recognition accuracy varied with tested images, when a resolution of 24 * 24
      was used: six of the eight image objects were recognized with an accuracy of
      >50%, and the remaining two of the eight image objects were recognized with an
      accuracy of <50%. Moreover, when the resolution is more than 32 * 32, the
      increase of the recognition accuracy is no longer obvious. We also have
      investigated the impact of different perspectives of the same object to the
      recognition accuracy. The experiment shows that providing multiview image
      sequences, subjects can receive more visual information to obtain higher
      recognition accuracy.

PMID- 21954833
TI  - Original article anti-oxidant pathways are stimulated by mesenchymal stromal
      cells in renal repair after ischemic injury.
AB  - BACKGROUND AIMS: Ischemia-reperfusion (IR) injury is a common cause of acute
      renal failure. Bone marrow (BM)-derived mesenchymal stromal cells (MSC) delivered
      after renal IR are renoprotective, but knowledge of the protective mechanism is
      still in development. This investigation analyzed the protective molecular
      mechanisms of MSC, in particular relating to modulated oxidative stress. METHODS:
      In vivo and in vitro models of renal IR were analyzed with and without MSC. In
      vivo, adult male Sprague-Dawley rats were subjected to 40-min unilateral renal
      IR. Rat BM-derived MSC were administered at 24 h post-IR (IR + MSC). Other groups
      had IR but no MSC, or MSC but no ischemia (all groups n = 4). Apoptosis,
      inflammation, oxidative stress and reparative signal transduction molecules or
      growth factors were studied 4 days post-IR. In vitro, protection by MSC against
      oxidative stress (0.4 mm hydrogen peroxide) was investigated using rat renal
      tubular epithelial cells (NRK52E) with or without MSC in co-culture (tissue
      culture trans-well inserts), followed by similar analyses to the in vivo
      investigation. RESULTS: In vivo, kidneys of IR + MSC animals had significantly
      increased cell proliferation/regeneration (cells positive for proliferating cell
      nuclear antigen, expression of epidermal growth factor), increased heme-oxygenase
      1 (improved cell survival, anti-oxidant) and decreased 8-OHdG (decreased
      oxidative stress). In vitro, MSC delivered with oxidative stress significantly
      decreased apoptosis and Bax (pro-apoptotic protein), and increased mitosis and
      phospho-ERK1/2, thereby minimizing the damaging outcome and maximizing the
      regenerative effect after oxidative stress. CONCLUSIONS: The benefits of MSC, in
      IR, were primarily pro-regenerative, sometimes anti-apoptotic, and novel anti
      oxidant mechanisms were identified.

PMID- 21954834
TI  - Enhancement of the immunosuppressive effect of human adipose tissue-derived
      mesenchymal stromal cells through HLA-G1 expression.
AB  - BACKGROUND AIMS: Mesenchymal stromal cells (MSC) from several tissues have
      immunomodulatory properties that involve various immunosuppressive molecules. An
      example is human leukocyte antigen (HLA)-G, a non-classical major
      histocompatibility complex (MHC) class I molecule that induces tolerance via
      interactions with inhibitory receptors present on major immune effector cells.
      Recently, the molecular mechanisms that regulate MSC-mediated immunosuppression
      have come under investigation. Our goal was to determine whether HLA-G plays a
      crucial role in immunosuppression and whether human adipose tissure (hAT) MSC can
      be used as a tool for biologic immunosuppression with HLA-G in transplantation.
      METHODS: MSC were characterized by fluorescence-activated cell sorting (FACS)
      analysis, reverse transcriptase (RT)-polymerase chain reaction (PCR) and staining
      for differentiation. The immunogenicity and immunomodulatory effects of MSC were
      monitored by peripheral blood mononuclear cell (PBMC) proliferation assay with or
      without phytohemagglutinin (PHA) stimulation. Stable expression of HLA-G1 in MSC
      was done using a lentiviral system. Results. MSC from different tissues had
      similar morphology, immunophenotypic characters and differentiation potential. We
      also found that the immunosuppressive effect of MSC was monitored along with
      their endogenous HLA-G mRNA and protein levels. Stable expression of HLA-G1
      appeared to enhance the immunosuppressive effect of hAT MSC, and the function of
      HLA-G1 was significantly decreased by HLA-G antagonistic antibody in PBMC
      proliferation assays. CONCLUSIONS: Although the HLA-G molecule is not the sole
      factor for MSC-mediated immunosuppression, our data provide evidence that HLA-G
      plays an important role in immunosuppression and that hAT MSC can be used as a
      tool for biologic immunosuppression during transplantation procedures.

PMID- 21954835
TI  - Increased apoptosis in cryopreserved autologous hematopoietic progenitor cells
      collected by apheresis and delayed neutrophil recovery after transplantation: a
      nested case-control study.
AB  - BACKGROUND AIMS: Delayed neutrophil recovery following autologous hematopoietic
      stem cell transplantation (aHSCT) increases transplant-related morbidity.
      Apoptosis induced by cryopreservation and thawing of hematopoietic progenitor
      cells collected by apheresis (HPC-A) was investigated in this nested case-control
      study as a factor associated with delayed neutrophil recovery following aHSCT.
      METHODS: Among patients with lymphoma who underwent aHSCT between 2000 and 2007
      (n = 326), 13 cases of primary delayed neutrophil recovery and 22 age- and sex
      matched controls were identified. Apoptosis and viability were measured using
      multiparameter flow cytometry, and colony-forming capacity was determined using
      semi-solid methylcellulose assays. RESULTS: HPC-A grafts from cases and controls
      had similar percentages of viable mononuclear cells (MNC) and CD34+ progenitor
      cells, as determined by standard 7AAD dye exclusion methods measured before and
      after cryopreservation. Patients with delayed neutrophil recovery received
      increased numbers of apoptotic MNC (P = 0.02) but similar numbers of apoptotic
      CD34+ cells per kilogram measured after thawing. Apoptosis was more pronounced in
      MNC compared with CD34+ cells after thawing, and apoptosis was negligible in
      freshly collected HPC-A products. Patients with delayed neutrophil recovery had
      fewer total colony-forming unites (CFU) and CFU-granulocyte-macrophages (GM) per
      10(5) viable post-thaw MNC compared with controls (P < 0.05). CONCLUSIONS:
      Increased numbers of apoptotic MNC in thawed HPC-A products are associated with
      delayed neutrophil recovery after aHSCT. Studies that address factors
      contributing to increased apoptosis are needed, and measuring apoptosis in thawed
      HPC-A may have a role in the assessment of graft adequacy.

PMID- 21954837
TI  - In vitro generation of influenza-specific polyfunctional CD4+ T cells suitable
      for adoptive immunotherapy.
AB  - BACKGROUND AIMS: Influenza viruses cause potentially fatal respiratory infections
      in stem cell transplant patients. Specific T cells provide long-lived host
      adaptive immunity to influenza viruses, and the potential for generating such
      cells for clinical use was investigated. METHODS: The inactivated influenza
      vaccine (Fluvax) approved for human use was used as the antigen source. Monocyte
      derived dendritic cells pulsed with Fluvax were used to stimulate autologous
      peripheral blood mononuclear cells (PBMC) on days 0 and 7. Cells were expanded
      with interleukin (IL)-2 from day 7 onwards. Cell numbers and phenotype were
      assessed on day 21. The presence of influenza virus-specific cells was assessed
      by cytokine production and proliferative responses following restimulation with
      influenza antigens. RESULTS: Over 21 days of culture, a mean fold increase of
      26.3 in cell number was observed (n = 7). Cultures were predominantly effector
      and central memory CD4+ cells, and expressed a phenotype characteristic of
      activated antigen-specific cells capable of B-cell helper function. Cytotoxic
      CD4+ and CD8+ cells specific for influenza and a high percentage of CD4+ cells
      specific for each of three influenza viruses targeted by Fluvax (H1N1, H3N2 and
      Brisbane viruses) were generated. In addition, T cells expanded when restimulated
      with antigens derived from influenza viruses. CONCLUSIONS: We have demonstrated a
      clinically usable method for producing influenza virus-specific T cells that
      yield high numbers of highly reactive CD4+ cells suitable for adoptive
      immunotherapy. We propose that reconstructing host immunity through adoptive
      transfer of influenza virus-specific T cells will reduce the frequency of
      influenza-related deaths in the period of severe immune suppression that follows
      stem cell transplantation.

PMID- 21954836
TI  - Conditioned medium from amniotic mesenchymal tissue cells reduces progression of
      bleomycin-induced lung fibrosis.
AB  - BACKGROUND AND AIMS: We have demonstrated recently that transplantation of
      placental membrane-derived cells reduces bleomycin-induced lung fibrosis in mice,
      despite a limited presence of transplanted cells in host lungs. Because placenta
      derived cells are known to release factors with potential immunomodulatory and
      trophic activities, we hypothesized that transplanted cells may promote lung
      tissue repair via paracrine-acting molecules. To test this hypothesis, we
      examined whether administration of conditioned medium (CM) generated from human
      amniotic mesenchymal tissue cells (AMTC) was able to reduce lung fibrosis in this
      same animal model. METHODS: Bleomycin-challenged mice were either treated with
      AMTC-CM or control medium, or were left untreated (Bleo group). After 9 and 14
      days, the distribution and severity of lung fibrosis were assessed histologically
      with a scoring system. Collagen deposition was also evaluated by quantitative
      image analysis. RESULTS: At day 14, lung fibrosis scores in AMTC-CM-treated mice
      were significantly lower (P < 0.05) compared with mice of the Bleo group, in
      terms of fibrosis distribution [1.0 (interquartile range, IQR 0.9) versus 3.0
      (IQR 1.8)], fibroblast proliferation [0.8 (IQR 0.4) versus 1.6 (IQR 1.0)],
      collagen deposition [1.4 (IQR 0.5) versus 2.0 (IQR 1.2)] and alveolar
      obliteration [2.3 (IQR 0.8) versus 3.2 (IQR 0.5)]. No differences were observed
      between mice of the Bleo group and mice treated with control medium. Quantitative
      analysis of collagen deposition confirmed these findings. Importantly, AMTC-CM
      treatment significantly reduced the fibrosis progression between the two
      observation time-points. CONCLUSIONS: This pilot study supports the notion that
      AMTC exert anti-fibrotic effects through release of yet unknown soluble factors.

PMID- 21954838
TI  - During epithelial differentiation of human adipose-derived stromal/stem cells,
      expression of zonula occludens protein-1 is induced by a combination of retinoic
      acid, activin-A and bone morphogenetic protein-7.
AB  - BACKGROUND AIMS: Adipose-derived stromal/stem cells (ASC) possess a multilineage
      differentiation potential, can be used from an autologous origin, and are,
      therefore, attractive candidates for clinical applications to repair or
      regenerate damaged tissues and organs. Beside their well-known differentiation
      into cells of mesodermal origin, ASC are able to differentiate into cells of ecto
      and endodermal origin. METHODS: Previous studies have shown that all trans
      retinoic acid (ATRA) induces the expression of cytokeratin 18 (CK18), indicating
      the beginning of differentiation into the epithelial lineage. Nevertheless, ATRA
      does not induce the expression of other epithelial markers. Therefore, we tested
      the additional influence of two growth factors on the onset of epithelial
      differentiation of ASC. The cells were cultured with ATRA, Activin A (ActA) and
      bone morphogenetic protein-7 (BMP-7), either alone or in combination.
      Differentiation into the epithelial lineage was assessed by the expression of the
      characteristic epithelial markers CK18 and zonula occludens protein 1 (ZO-1)
      using Western blot, immunofluorescence staining and polymerase chain reaction
      (PCR) analysis. RESULTS: The mixture of all three factors induced epithelial
      differentiation of ASC without enhancing cell proliferation. Upon induction, the
      ASC showed phenotypic changes consistent with an epithelial phenotype. The
      addition of the growth factors ActA and BMP-7 enhanced the inductive effect of
      ATRA, as shown by the de novo expression of ZO-1 in addition to CK18 expression.
      CONCLUSIONS: Our study highlights the onset of the epithelial differentiation of
      ASC induced by culture with a combination of ATRA, ActA and BMP-7.

PMID- 21954839
TI  - Mesenchymal stromal cell transplantation in amyotrophic lateral sclerosis: a long
      term safety study.
AB  - BACKGROUND AIMS: Mesenchymal stem cells/marrow stromal cells (MSC) represent a
      promising tool for stem cell-based clinical trials in amyotrophic lateral
      sclerosis (ALS). We present the results of long-term monitoring of 19 ALS
      patients enrolled in two phase I clinical trials of autologous MSC
      transplantation. METHODS: Nineteen patients (11 male and eightfemale) with ALS
      were enrolled in two consecutive phase I clinical trials. The patients were
      followed-up for 6-9 months and then treated with autologous MSC isolated from
      bone marrow and implanted into the dorsal spinal cord with a surgical procedure.
      The patients were monitored regularly before and after transplantation with
      clinical, psychological and neuroradiologic assessments every 3 months, at the
      tertiary referral ALS center in Novara (Italy), until death. RESULTS: Follow-up
      brain magnetic resonance imaging (MRI) revealed no structural changes (including
      tumor formation) relative to the baseline throughout the follow-up. There was no
      deterioration in the psychosocial status and all patients coped well. No clear
      clinical benefits were detected in these patients but the recruitment and
      selection of appropriate patients into larger trials will be needed to test the
      efficacy of the treatment. CONCLUSIONS: This study is the first to show the
      safety of MSC transplantation in the central nervous system during a follow-up of
      nearly 9 years, and is in support of applying MSC-based cellular clinical trials
      to neurodegenerative disorders.

PMID- 21954840
TI  - The internal cranial morphology of an armoured dinosaur Euoplocephalus
      corroborated by X-ray computed tomographic reconstruction.
AB  - Internal cranial anatomy is a challenging area to study in fossilized skulls
      because of small sample sizes and varied post-mortem preservational alterations.
      This difficulty has led to the lack of correspondence between results obtained
      from direct osteological observation and from more indirect reconstruction
      methods. This paper presents corroborating evidence from direct osteological
      observation and from reconstruction based on computed X-ray tomography (CT) on
      the internal cranial anatomy of the ankylosaurid dinosaur Euoplocephalus tutus. A
      remarkable specimen of Euoplocephalus preserves rarely observed internal cranial
      structures such as vascular impressions in the nasal cavity, olfactory turbinates
      and possible impressions of conchae. Comparison with fossils and CT models of
      other taxa and other Euoplocephalus specimens adds osteological evidence for the
      previously reconstructed nasal cavity in this dinosaur and revises the previously
      described braincase morphology. A new interpretation of the ethmoidal homology
      identifies a mesethmoid, sphenethmoid and ectethmoid. These ethmoidal
      ossifications are continuous with the mineralized walls of the nasal cavity. The
      location of the olfactory fenestra provides further evidence that the olfactory
      regions of the nasal cavity are pushed to the sides of the main airway. This
      implies that the function of the vascular impressions in the nasal cavity and the
      looping of the cavity are not related to olfaction. A byproduct of the elongate,
      looping airway is a dramatic increase in surface area of the nasal respiratory
      mucosa, which in extant species has been linked to heat and water balance. A role
      in vocalization as a resonating chamber is another possible function of the
      looping and elongation of the nasal cavity. Olfaction remains as a possible
      function for the enlarged olfactory region, suggesting that multiple functions
      account for different parts of the ankylosaurid nasal cavity that underwent
      substantial modification. Cranial endocasts show negligible variation within
      Euoplocephalus, which lends some confidence to interspecific comparisons of
      endocranial morphology.

PMID- 21954841
TI  - Fick diffusion coefficients of liquid mixtures directly obtained from equilibrium
      molecular dynamics.
AB  - A methodology for computing Fick diffusivities directly from equilibrium
      molecular dynamics (MD) simulations is presented and validated for acetone
      methanol and acetone-tetrachloromethane liquid mixtures. Fick diffusivities are
      obtained from Maxwell-Stefan (MS) diffusivities and the so-called thermodynamic
      factor. MS diffusivities describe the friction between different components,
      while the thermodynamic factor is the concentration derivative of the activity
      describing the deviation from ideal mixing behavior. It is important to note that
      all mutual diffusion experiments measure Fick diffusion coefficients, while
      molecular simulation provides MS diffusivities. The required thermodynamic factor
      to convert MS into Fick diffusivities and vice versa, however, is usually
      difficult to extract from both simulations and experiments leaving a gap between
      theory and application. Here, we employ our novel method to compute the
      thermodynamic factor from small-scale density fluctuations in equilibrium MD
      simulations [Chem. Phys. Lett.2011, 504, 199-201]. Previously, this method was
      developed and validated for molecules with single interaction sites only. In this
      work, we applied this method to acetone-methanol and acetone-tetrachloromethane
      liquid mixtures and show that the method also works well in these more complex
      systems. This provides the missing step to extract Fick diffusion coefficients
      directly from equilibrium MD simulations. The computed Fick diffusivities of
      acetone-methanol and acetone-tetrachloromethane mixtures are in excellent
      agreement with experimental values. The suggested framework thus provides an
      efficient route to model diffusion in liquids on the basis of a consistent
      molecular picture.

PMID- 21954842
TI  - The retained surgical specimen, an unappreciated retained foreign object.
AB  - A retained foreign object is a preventable surgical error and has typically been
      considered a surgical instrument, needle, or sponge. A new retained surgical
      object is a retained surgical specimen (RSS). This case study outlines the nature
      of the RSS, the paradigm shift that has led to this becoming a new healthcare
      error, and steps to prevent this new type of retained object from occurring.

PMID- 21954843
TI  - PPAR-gamma activator pioglitazone prevents age-related atrial fibrillation
      susceptibility by improving antioxidant capacity and reducing apoptosis in a rat
      model.
AB  - INTRODUCTION: The in vivo role of peroxisome proliferator-activated receptor
      (PPAR)-gamma, an essential transcriptional mediator of lipid and glucose
      metabolism, in atrial fibrillation (AF) remains to be fully elucidated. We
      investigated the effects of pioglitazone, a PPAR-gamma activator, in an in vivo
      AF rat model. METHODS AND RESULTS: We studied 3 groups of Wistar rats: young
      group, 3-month-old rats treated with vehicle; aged group, 9-month-old rats
      treated with vehicle; and aged+Pio group, 9-month-old rats treated with
      pioglitazone. After 4-week treatment, AF duration induced by 30-second burst
      pacing, gene and protein expressions, and atrial structural changes were compared
      between the 3 groups. Atrial oxidant reducing activity was measured by electron
      spin resonance method. AF duration was markedly prolonged in the aged group but
      significantly shortened in the aged+Pio group. Age-induced decrease in free
      radical reducing activity was reversed by pioglitazone. Gene and protein
      expression levels of antioxidant molecules Sod2 (MnSOD) and Hspa1a (heat shock 70
      protein) were significantly enhanced, and p22(phox) and gp91(phox), two NADPH
      oxidase subunits, were significantly decreased in aged+Pio rats. Pioglitazone
      treatment significantly increased phosphorylated (p-) Akt but significantly
      reduced p-ERK1/2 and p-JNK. Pioglitazone significantly restored p-Bad and reduced
      cleaved caspase-3 and -9, indicating that pioglitazone prevented age-related
      enhancement of apoptotic signaling. Microscopic analysis revealed suppression of
      age-related histological changes (interstitial fibrosis and apoptosis) by
      pioglitazone. CONCLUSIONS: Pioglitazone inhibited age-related arrhythmogenic
      atrial remodeling and AF perpetuation by improving antioxidant capacity and
      inhibiting the mitochondrial apoptotic signaling pathway. PPAR-gamma activators
      could become a novel upstream therapy for age-related AF.

PMID- 21954845
TI  - Porous CdTe nanocrystal assemblies: ligation effects on the gelation process and
      the properties of resultant aerogels.
AB  - Highly porous CdTe nanoarchitectures (aerogels) were prepared by sol-gel assembly
      of discrete nanocrystals followed by supercritical CO(2) drying. CdTe nanocrystal
      surface functionalization (either phosphine oxide or thiolate) is found to be
      immaterial to oxidation induced gel formation suggesting that the standard
      thiolate capping procedure is not a necessary step in the gelation process. On
      the basis of this observation, and reduction induced dispersion of the gel
      network, the exposure of reactive sites and the subsequent surface oxidation
      reaction to form polychalcogenide linkages are key steps in the gelation
      mechanism. Consequently, CdTe aerogels exhibit similar physicochemical
      properties, regardless of original ligating functionality. The aerogels are
      mesoporous, with surface area >100 m(2)/g, and exhibit an optical bandgap of 1.92
      eV, consistent with quantum confinement within the 3-D linked network.
      Photoluminescence is suppressed in the aerogels, but can be partially recovered
      upon heating.

PMID- 21954844
TI  - Social-emotional effects of early childhood education programs in Tulsa.
AB  - This article assesses the effects of Tulsa, Oklahoma's early childhood education
      programs on social-emotional outcomes, examining teacher ratings of children's
      behavior from the Adjustment Scales for Preschool Intervention and a measure of
      attentiveness using fixed effects regressions with propensity score matching. The
      sample includes 2,832 kindergarten students in 2006, of whom 1,318 participated
      in the Tulsa Public Schools (TPS) pre-K program and 363 participated in the CAP
      of Tulsa County Head Start program the previous year. Program participation was
      associated with lower timidity and higher attentiveness for TPS pre-K alumni and
      a marginally significant reduction in timidity for Head Start alumni. Results
      were similar for the free lunch-eligible subsample. We conclude that high
      quality, school-based preschool programs can enhance social-emotional
      development.

PMID- 21954846
TI  - Severely overweight children and dietary changes--a family perspective.
AB  - AIM: This article is a report on a descriptive qualitative case study of the
      dietary change experiences of overweight children and their families. BACKGROUND:
      Obese children are at risk of experiencing a complicated childhood and becoming
      obese adults with associated ill health and premature death. The prevalence of
      obesity among children appears to be rising rapidly. In Europe, prevalence rates
      for overweight children are 10-40%, and generally this prevalence has tripled
      during the past 30 years. METHOD: The study was conducted as a qualitative
      longitudinal case study on the basis of 2-3 annual interviews with four
      overweight Danish children, six parents and four siblings from April 2006 to
      September 2008. Altogether 61 interviews were conducted. In the data analysis
      process, a thematic, phenomenological approach was used. FINDINGS: The following
      themes were identified: the reactions and attitudes of children with the sub
      themes taking ownership of dietary changes and vulnerability reactions; and the
      reactions and attitudes of parents with the sub-themes personal acceptance and
      support, indulgence and protection, setting limits and barriers to successful
      dietary change. The children were under pressure, showed signs of stigmatization
      and marginalization, and developed self-protecting strategies. The parents tried
      to cope to the best of their ability, needed help, but felt rejected by
      professional key persons and authorities. CONCLUSIONS: On the basis of the study,
      it was hypothesised that a prejudice-free, individually accepting and supporting
      intervention must be provided for each family over time to ensure successful
      weight loss.

PMID- 21954847
TI  - Cross-talk between human mesenchymal stem/progenitor cells (MSCs) and rat
      hippocampal slices in LPS-stimulated cocultures: the MSCs are activated to
      secrete prostaglandin E2.
AB  - Mesenchymal stem/progenitor cells (MSCs) improve functional outcome in a number
      of disease models through suppression of inflammation. However, their effects on
      neuroinflammation are unknown. In this study, we show that MSCs suppress
      endotoxin-induced glial activation in organotypic hippocampal slice cultures
      (OHSCs). Lipopolysaccharide-stimulated OHSCs activated MSCs to increase the
      expression of cyclo-oxygenase-2 and produce prostaglandin E2. MSC-derived
      prostaglandin E2, then suppressed pro-inflammatory cytokine production by the
      OHSCs. Together, the results suggest the potential anti-inflammatory mechanism of
      MSCs in models of disease and support earlier observations that MSCs may offer a
      therapy for neuroinflammation produced by trauma or disease.

PMID- 21954848
TI  - Cardiac performance is impaired in morbidly obese pregnant females.
AB  - AIM: To evaluate the effect of pregnancy on ventricular function in morbidly
      obese as compared to lean controls. MATERIAL AND METHODS: We serially studied 33
      obese and non-obese pregnant females with echocardiography during each trimester
      of pregnancy and after delivery. Two well-validated, relatively load-independent
      indices of contractility (systolic shortening index and systolic velocity index)
      were assessed, along with more traditional echocardiographic parameters. ANOVA
      for repeated measures was used to compare data between sequential studies in the
      normal and obese pregnant groups. RESULTS: In lean controls, stroke volume
      increased and contractility was maintained during pregnancy as compared to pre
      pregnancy levels. In contrast, both stroke volume and contractility declined
      significantly by the third trimester in morbidly obese females. CONCLUSION: There
      is a maladaptive left ventricular contractile response to pregnancy in morbidly
      obese patients.

PMID- 21954849
TI  - Ab initio benchmark calculations on Ca(II) complexes and assessment of density
      functional theory methodologies.
AB  - A set of benchmark results for the geometries, binding energies, and protonation
      affinities of 24 complexes of small organic ligands with Ca(II) is provided. The
      chosen level of theory is CCSD(T)/CBS obtained by means of a composite procedure.
      The performance of four density functionals, namely, PW91, PBE, B3LYP, and TPSS
      and several Pople-type basis sets, namely, 6-31G(d), 6-31+G(d), 6-31+G(2d,p) and
      6-311+G(d) have been assessed. Additionally, the nature of the metal ligand
      bonding has been analyzed by means of the Symmetry Adapted Perturbation Theory
      (SAPT). We have found that the B3LYP hybrid functional, in conjunction with
      either the polarized double-zeta 6-31+G(2d,p) or the triple-zeta 6-311+G(d) basis
      sets, yields the closest results compared to the benchmark data. The SAPT
      analysis stresses the importance of induction effects in the binding of these
      complexes and suggests that consideration of classical electrostatic
      contributions alone may not be reliable enough for the prediction of relative
      binding energies for Ca(II) complexes.

PMID- 21954850
TI  - Lives of quality in the face of challenge in Israel.
AB  - PURPOSE: The purpose of this study is to describe and analyse the quality of life
      of Israeli families raising a child with a disability while challenged with all
      the usual demands of family life. METHODS: Respondents were main caregivers of
      103 children with disability receiving services at Beit Issie Shapiro, a service
      agency in Israel. The respondents completed the Family Quality of Life Survey
      2006 which operationalises family quality of life (FQOL) as a construct in nine
      domains of family life. FINDINGS: The findings show an underlying pattern within
      the domains that define FQOL. In general, the findings indicate that the families
      are strongly challenged to meet the needs of a special child and raise a family
      meeting the needs of all its members. The respondents report that, within the
      limits of available opportunities, they had achieved well and they are satisfied
      with their attainment. In general, our findings seem to reflect in our
      respondents a sense of resilience and an ability to manage family challenges to
      achieve a reasonably high FQOL. Domains described as internal to the family were
      rated highly in terms of FQOL as compared to domains external to the family.
      CONCLUSION: The Family Quality of Life Survey-2006 was found to be a valuable
      tool for identifying and evaluating factors that enhance FQOL. Further research
      is needed to develop application models for integrating this instrument into the
      agency's service and evaluation repertoire.

PMID- 21954851
TI  - Diterpenes from the Hainan soft coral Lobophytum cristatum Tixier-Durivault.
AB  - Two new prenylgermacrane-type diterpenoids, lobophytumins A and B (1 and 2), two
      new prenyleudesmane-type diterpenoids, lobophytumins C and D (3 and 4), and two
      new spatane-type diterpenoids, lobophytumins E and F (5 and 6), were isolated
      from the Hainan soft coral Lobophytum cristatum Tixier-Durivault. Their
      structures, including relative configuration, were elucidated by detailed
      analysis of spectroscopic data and by comparison with related known compounds. In
      addition, the absolute configuration of lobophytumin C (3) was tentatively
      assigned by comparing its specific rotation with that of the closely related
      model compound (-)-beta-selinene (8). On the basis of biogenetic considerations,
      the absolute configurations of lobophytumins A, B, and D-F were also tentatively
      suggested. This is the first report of spatane-type diterpenoids from a soft
      coral source. The present work supports Faulkner's proposal of prenylgermacrene
      as the precursor of many diterpenes. In a bioassay, lobophytumins C and D (3 and
      4) showed weak in vitro cytotoxicities against the tumor cell lines A-549 and HCT
      116.

PMID- 21954852
TI  - Bioavailability of beta-cryptoxanthin in the presence of phytosterols: in vitro
      and in vivo studies.
AB  - Bioactive compounds are used in the design and development of new food products
      with potential health benefits, although little is known regarding their
      bioavailability and interactions. This study assessed the stability, in vitro
      bioaccessibility, and human bioavailability of beta-cryptoxanthin from beta
      cryptoxanthin-rich drinks with and without added phytosterols developed for this
      purpose. The developed drinks showed no difference in the content of beta
      cryptoxanthin, and they were stable over 6 months. In vitro, hydrolysis of beta
      cryptoxanthin esters and the amount of free beta-cryptoxanthin at duodenal and
      micellar phases were similar regardless of the presence of phytosterols. In the
      human study, the daily intake provoked significant increments of beta
      cryptoxanthin in serum regardless of the type of the drink. In conclusion, in
      vitro and in vivo human studies have shown that the bioavailability of beta
      cryptoxanthin is not significantly affected by the presence of phytosterols when
      they are simultaneously supplied in a drink.

PMID- 21954853
TI  - Omega-3 docosahexaenoic acid and procyanidins inhibit cyclo-oxygenase activity
      and attenuate NF-kappaB activation through a p105/p50 regulatory mechanism in
      macrophage inflammation.
AB  - The inflammatory response has been implicated in the pathogenesis of many chronic
      diseases. Along these lines, the modulation of inflammation by consuming
      bioactive food compounds, such as omega-3 fatty acids or procyanidins, is a
      powerful tool to promote good health. In the present study, the administration of
      DHA (docosahexaenoic acid) and B1, B2 and C1 procyanidins, alone or in
      combination, prevented the inflammatory response induced by the LPS
      (lipopolysaccharide) endotoxin in human macrophages and brought them to the
      homoeostatic state. DHA and B1 were strong and selective negative regulators of
      cyclo-oxygenase 1 activity, with IC50 values of 13.5 MUM and 8.0 MUM
      respectively. Additionally, B2 and C1 were selective inhibitors of pro
      inflammatory cyclo-oxygenase 2 activity, with IC50 values of 9.7 MUM and 3.3 MUM
      respectively. Moreover, DHA and procyanidins prevented the activation of the NF
      kappaB (nuclear factor kappaB) cascade at both early and late stages with shared
      mechanisms. These included inhibiting IkappaBalpha (inhibitor of NF-kappaB alpha)
      phosphorylation, inducing the cytoplasmic retention of pro-inflammatory NF-kappaB
      proteins through p105 (NF-kappaB1) overexpression, favouring the nuclear
      translocation of the p50-p50 transcriptional repressor homodimer instead of the
      p50-p65 pro-inflammatory heterodimer, inhibiting binding of NF-kappaB DNA to
      kappaB sites and, finally, decreasing the release of NF-kappaB-regulated
      cytokines and prostaglandins. In conclusion, DHA and procyanidins are strong and
      selective inhibitors of cyclo-oxygenase activity and NF-kappaB activation through
      a p105/p50-dependent regulatory mechanism.

PMID- 21954854
TI  - Structure-directing roles and interactions of fluoride and organocations with
      siliceous zeolite frameworks.
AB  - Interactions of fluoride anions and organocations with crystalline silicate
      frameworks are shown to depend subtly on the architectures of the organic
      species, which significantly influence the crystalline structures that result.
      One- and two-dimensional (2D) (1)H, (19)F, and (29)Si nuclear magnetic resonance
      (NMR) spectroscopy measurements establish distinct intermolecular interactions
      among F(-) anions, imidazolium structure-directing agents (SDA(+)), and
      crystalline silicate frameworks for as-synthesized siliceous zeolites ITW and
      MTT. Different types and positions of hydrophobic alkyl ligands on the
      imidazolium SDA(+) species under otherwise identical zeolite synthesis
      compositions and conditions lead to significantly different interactions between
      the F(-) and SDA(+) ions and the respective silicate frameworks. For as
      synthesized zeolite ITW, F(-) anions are established to reside in the double-four
      ring (D4R) cages and interact strongly and selectively with D4R silicate
      framework sites, as manifested by their strong (19)F-(29)Si dipolar couplings. By
      comparison, for as-synthesized zeolite MTT, F(-) anions reside within the 10-ring
      channels and interact relatively weakly with the silicate framework as ion pairs
      with the SDA(+) ions. Such differences manifest the importance of interactions
      between the imidazolium and F(-) ions, which account for their structure
      directing influences on the topologies of the resulting silicate frameworks.
      Furthermore, 2D (29)Si{(29)Si} double-quantum NMR measurements establish (29)Si-O
      (29)Si site connectivities within the as-synthesized zeolites ITW and MTT that,
      in conjunction with synchrotron X-ray diffraction analyses, establish insights on
      complicated order and disorder within their framework structures.

PMID- 21954855
TI  - Indoor air pollution and lung function growth among children in four Chinese
      cities.
AB  - Ambient air pollution has been associated with decreased growth in lung function
      among children; but little is known about the impact of indoor air pollution. We
      examined relationships between indoor air pollution metrics and lung function
      growth, among children (n = 3273) aged 6-13 years living in four Chinese cities.
      Lung function parameters (FVC and FEV(1) ) were measured twice a year.
      Questionnaires were used to determine home coal burning and ventilation
      practices. Generalized estimating equations were used to examine associations.
      Use of coal as a household fuel was associated with 16.5 ml/year lower (33%, P <
      0.001) and 20.5 ml/year lower (39%, P < 0.001) growth in children's FEV(1) and
      FVC, respectively. FEV(1) growth was 10.2 ml/year higher (20%, P = 0.009), and
      FVC growth was 17.0 ml/year higher (33%, P < 0.001) among children who lived in
      houses with the presence of a ventilation device. Among children living in houses
      where coal was used as a fuel and no ventilation devices were present, adjusted
      FVC and FEV(1) growth, respectively, were 37% and 61% that of the average growth
      per year in the full cohort. This suggests that household coal use may cause
      deficits in lung function growth, while using ventilation devices may be
      protective of lung development. PRACTICAL IMPLICATIONS: Nearly 3.4 billion people
      use solid fuels in homes for cooking and/or heating. We report the following
      findings from a longitudinal study: (i) household coal use is significantly
      associated with reduction in children's lung function growth and (ii) the use of
      household ventilation devices is significantly associated with higher lung
      function growth, particularly among children living in households where coal is
      used as a fuel. These findings not only provide evidence that indoor coal use
      impairs children's lung development but also point to the importance of improving
      ventilation conditions in reducing harmful effects of indoor air pollution
      sources.

PMID- 21954856
TI  - Transient alkalinization in the leaf apoplast of Vicia faba L. depends on NaCl
      stress intensity: an in situ ratio imaging study.
AB  - The apoplast is suggested to be involved not only in the response, but also in
      the perception and transduction of various environmental signals. In this
      context, apoplastic alkalinization has previously been discussed as a general
      stress factor caused by abiotic and biotic stress events. In this study, an ion
      sensitive fluorescence probe in combination with inverted fluorescence microscopy
      has been used for in planta monitoring of apoplastic shoot pH during challenging
      of Vicia faba L. plants by NaCl stress encountered at the roots. We demonstrate
      that transient increases in leaf apoplastic pH are dependent on the NaCl stress
      intensity. Moreover, we have visualized spatial pH gradients within the leaf
      apoplast. Our results indicate that these pH responses are propagated from root
      to leaf and that this occurs along the apoplast.

PMID- 21954857
TI  - Marmosa paraguayana (Marsupialia: Didelphidae) as a new host for Gracilioxyuris
      agilisis (Nematoda: Oxyuridae) in Brazil.
AB  - Didelphids (Didelphimorphia: Didelphidae) are a large and well-studied group of
      Neotropical marsupials. Although knowledge of the parasitic fauna of didelphids
      is still scarce, recent work has suggested that Neotropical marsupials are often
      hosts of pinworms. Here, we isolated oxyurid nematodes from fecal samples of
      Marmosa paraguayana (Marsupialia: Didelphidae) and provide a general description
      and measurements for male and female specimens. We concluded these specimens can
      be assigned to Gracilioxyuris agilisis (Ascaridida: Oxyuridae), an oxyurid
      recently described as a parasite of the didelphid Gracilinanus agilis
      (Didelphimorphia: Didelphidae). The finding of G. agilisis in a different, albeit
      closely related, host species strengthens the previous notion of a close
      association between pinworms and didelphids and contributes to the knowledge of
      the helminthic fauna of didelphid marsupials.

PMID- 21954858
TI  - An empirical approach to evaluating the validity of alternative low-risk drinking
      guidelines.
AB  - INTRODUCTION AND AIMS: This paper proposes an approach for evaluating the
      validity of alternative low-risk drinking guidelines. DESIGN AND METHODS: Twenty
      seven alternative guidelines were evaluated in terms of their ability to predict
      nine measures of concurrent and prospective alcohol-related harm, using
      longitudinal data from a nationally representative sample of US adults (n = 26
      438 to 12 339 depending upon outcome). Parameters compared included sensitivity,
      specificity, adjusted odds ratios and measures of model fit. RESULTS: Performance
      varied by harm. The guidelines that best predicted concurrent alcohol-related
      harm comprised daily-only limits of 4/3 drinks for men/women, but gender
      invariant limits of 4/4 drinks also performed well. Adding weekly limits did
      little to improve the prediction of concurrent harm. The guidelines that best
      predicted prospective harm comprised daily limits of 4/4 drinks combined with
      weekly limits of 14 drinks for men and 7 drinks for women, with weekly limits of
      14/14 drinks running second. When concurrent and incident harms were aggregated,
      daily-only limits of 4/3 drinks performed nearly on a par with the combination of
      14/14 drinks per week and 4/3 drinks per day. DISCUSSION AND CONCLUSIONS: This
      paper supported gender-specific daily limits and suggested that optimal
      guidelines might take daily limits from analyses of concurrent harms and weekly
      limits from analyses of prospective harms. This paper illustrates a mechanism for
      validating the ability of low-risk drinking guidelines to accurately predict a
      range of alcohol-related harms, whereby countries could use their own data on
      consumption and its association with harm to evaluate their low-risk drinking
      guidelines

PMID- 21954859
TI  - Cytoskeletal reorganization mediates fluid shear stress-induced ERK5 activation
      in osteoblastic cells.
AB  - Mechanotransduction is a complicated process, of which mechanosensation is the
      first step. Previous studies have shown that the cytoskeleton plays a crucial
      role in mechanosensation and the mediation of intracellular signal transduction.
      However, the mechanism of mechanotransduction in the bone remains elusive. Here,
      we investigated the potential involvement of a novel MAPK (mitogen-activated
      protein kinase) member, ERK5 (extracellular-signal-regulated kinase 5), in the
      response of osteoblastic cells to FSS (fluid shear stress). Our results
      demonstrated that ERK5 was rapidly phosphorylated in pre-osteoblastic MC3T3-E1
      cells upon FSS, and the integrity and reorganization of the cytoskeleton were
      critical in this process, in which the cytoskeleton-dependent activation of FAK
      (focal adhesion kinase) may be involved in the activation of ERK5 induced by FSS.
      Moreover, we found that cytoskeletal disruption led to significant down
      regulation of ERK5 phosphorylation, but had no effect on ERK5 nuclear
      localization. Furthermore, the cytoskeleton rapidly reorganized in response to
      FSS, but long-time fluid load, even at a physiological level, led to cytoskeletal
      disruption, suggesting that other pathways may be involved in long-term
      mechanotransduction. Taken together, our data provide new insight into the
      mechanisms of mechanosensation by highlighting the link between ERK5 activation
      and cytoskeletal reorganization in osteoblasts undergoing FSS.

PMID- 21954860
TI  - Noncovalent PEGylation by polyanion complexation as a means to stabilize
      keratinocyte growth factor-2 (KGF-2).
AB  - Repifermin, a truncated form of fibroblast growth factor-10 (FGF-10) also known
      as keratinocyte growth factor-2 (KGF-2), is a heparin-binding protein with potent
      regenerative properties. The protein unfolds and aggregates at relatively low
      temperature (~37  degrees C). Electrostatic interactions between polyanions and
      several FGFs have been reported to enhance the thermal stability of these
      proteins. Polyethylene glycol (PEG) was grafted to the polyanions pentosan
      polysulfate (PPS) and dextran sulfate (DS) as an alternative means to stabilize
      and noncovalently PEGylate KGF-2. Physical characteristics of KGF-2:polyanion-PEG
      complexes were examined using a variety of methods including circular dichroism
      (CD), intrinsic tryptophan fluorescence, differential scanning calorimetry, and
      dynamic light scattering. When compared to KGF-2 alone, subtle changes in CD
      spectra and fluorescence emission maxima were found when KGF-2 was formulated
      with the synthetic PEG-polyanions. Highly PEGylated polyanions (DS-PEG5) did not
      bind KGF-2 as well as conjugates with fewer PEG chains. The molecular weight of
      PEG did not have a noticeable effect on KGF-2 binding to the various PEG
      polyanion conjugates. At optimal molar ratios, PPS-PEG and DS-PEG conjugates were
      able to stabilize KGF-2 by increasing the melting temperature by approximately 9
      17  degrees C. Thus, polyanion-PEG conjugates improved the stability of KGF-2 and
      also offered a new electrostatic PEGylation scheme that may be extrapolated to
      other heparin-binding proteins.

PMID- 21954861
TI  - Chameleonic behavior of ionic liquids and its impact on the estimation of
      solubility parameters.
AB  - The possibility of developing a scale for solubility parameters, with the purpose
      of predicting the performance and aiding the selection of ILs, was evaluated. For
      the estimation of solubility parameters, infinite-dilution activity coefficient
      data were used. The results allowed the identification of a curious behavior for
      ILs that seem to present more than one solubility parameter, acting as polar
      molecules in some situations and as nonpolar molecules in others, depending on
      the medium. This behavior was confirmed by solubility measurements of
      [C(4)MIM][PF(6)] in solvent mixtures. In this work, the solubility parameters
      were also estimated from other properties, namely, viscosities and enthalpies of
      vaporization, and the relation between the various sets of solubility parameters
      is discussed. The results obtained suggest that, given the complexity of IL
      molecules and their liquid phases, a one-dimensional scale for solubility
      parameters that is able to characterize these fluids is not feasible.

PMID- 21954862
TI  - Demonstration of submersible high-throughput microfluidic immunosensors for
      underwater explosives detection.
AB  - Significant security threats posed by highly energetic nitroaromatic compounds in
      aquatic environments and the demilitarization and pending cleanup of areas
      previously used for munitions manufacture and storage represent a challenge for
      less expensive, faster, and more sensitive systems capable of analyzing
      groundwater and seawater samples for trace levels of explosive materials.
      Presented here is an inexpensive high throughput microfluidic immunosensor (HTMI)
      platform intended for the rapid, highly selective quantitation of nitroaromatic
      compounds in the field. Immunoaffinity and fluorescence detection schemes were
      implemented in tandem on a novel microfluidic device containing 39 parallel
      microchannels that were 500 MUm tall, 250 MUm wide, and 2.54 cm long with
      covalently tethered antibodies that was engineered for high-throughput high
      volume sample processing. The devices were produced via a combination of high
      precision micromilling and hot embossing. Mass transfer limitations were found in
      conventional microsystems and were minimized due to higher surface area to volume
      ratios that exceeded those possessed by conventional microdevices and
      capillaries. Until now, these assays were limited to maximum total volume flow
      rates of ~1 mL/min due in part to kinetics and high head pressures of single
      microchannels. In the design demonstrated here, highly parallelized microchannels
      afforded up to a 100-fold increase in total volume flow rate while maintaining
      favorable kinetic constraints for efficient antigen-antibody interaction. The
      assay employed total volume throughput of up to 6 mL/min while yielding signal-to
      noise ratios of >15 in all cases. In addition to samples being processed up to 60
      times faster than in conventional displacement-based immunoassays, the current
      system was capable of quantitating 0.01 ng/mL TNT samples without implementing
      offline preconcentration, thereby, demonstrating the ability to improve
      sensitivity by as much as 2 orders of magnitude while decreasing total analysis
      times up to 60-fold.

PMID- 21954863
TI  - Optimization of the enzymatic deamidation of soy protein by protein-glutaminase
      and its effect on the functional properties of the protein.
AB  - The effects of enzymatic deamidation by protein-glutaminase (PG) on the
      functional properties of soy protein isolate (SPI) were studied. Conditions for
      the deamidation were evaluated by means of response surface methodology (RSM).
      Optimal conditions based on achieving a high degree of deamidation (DD) with a
      concurrently low degree of hydrolysis (DH) were 44  degrees C, enzyme:substrate
      ratio (E/S) of 40 U/g protein and pH 7.0. Under optimal conditions, both DD and
      DH increased over time. SDS-PAGE results indicated that lower molecular mass
      subunits were produced with increasing DD. Far-UV circular dichroism spectra
      revealed that the alpha-helix structure decreased with higher DD, while the beta
      sheet structure increased until 15 min of deamidation (32.9% DD), but then
      decreased at higher DD. The solubility of deamidated SPI was enhanced under both
      acidic and neutral conditions. SPI with higher DD showed better emulsifying
      properties and greater foaming capacity than SPI, while foaming stability was
      decreased. It is possible to modify and potentially improve the functional
      properties of SPI by enzymatic deamidation using PG.

PMID- 21954864
TI  - Antiangiogenic effect of chamigrane endoperoxides from a Thai mangrove-derived
      fungus.
AB  - As part of our ongoing efforts to investigate natural products with potential for
      use as cancer treatments, we have recently disclosed the cytotoxicity of unique
      nor-chamigrane (1) and chamigrane (2, 3) endoperoxides from a Thai mangrove
      derived fungus. Reinvestigation of this fungus in a large-scale fermentation led
      to the isolation of an additional new chamigrane endoperoxide (4) and one known
      analogue (5). Among these isolated metabolites, compound 3 (merulin C) exhibited
      potent antiangiogenic activity mainly by suppression of endothelial cell
      proliferation and migration in a dose-dependent manner, and its effect is
      mediated by reduction in the phosphorylation of Erk1/2. Merulin C also displayed
      promising activity in a rat aortic ring sprouting (ex vivo) and a mouse Matrigel
      (in vivo) assay.

PMID- 21954865
TI  - The pyrolysis of isoxazole revisited: a new primary product and the pivotal role
      of the vinylnitrene. A low-temperature matrix isolation and computational study.
AB  - This paper describes the pyrolysis of parent isoxazole and of its 5-methyl and
      3,5-dimethyl derivatives by the high-pressure pulsed pyrolysis method, where
      activation of the precursor molecules occurs predominantly by collisions with the
      host gas (Ar in our case), rather than with the walls of the pyrolysis tube,
      where catalyzed processes may occur. The products were trapped at 15 K in Ar
      matrices and were characterized by vibrational spectroscopy. Thereby, hitherto
      unobserved primary products of pyrolysis of isoxazole and of its 5-methyl
      derivative, 3-hydroxypropenenitrile or 3-hydroxybutenenitrile, respectively, were
      observed. E-Z photoisomerization could be induced in the above hydroxynitriles.
      On pyrolysis of isoxazole, ketenimine and CO were observed as decomposition
      products, but this process did not occur when the 5-methyl derivative was
      pyrolyzed. Instead, the corresponding ketonitrile was formed. In the case of 3,5
      dimethylisoxazole, 2-acetyl-3-methyl-2H-azirine was detected at moderate
      pyrolysis temperatures, whereas at higher temperatures, 2,5-dimethyloxazole was
      the only observed rearrangement product (next to products of dissociation). These
      findings are rationalized on the basis of quantum chemical calculations. Thereby
      it becomes evident that carbonyl-vinylnitrenes play a pivotal role in the
      observed rearrangements, a role that had not been recognized in previous
      theoretical studies because it had been assumed that vinylnitrenes are closed
      shell singlet species, whereas they are in fact open-shell singlet biradicaloids.
      Thus, the primary processes had to be modeled by the multiconfigurational CASSCF
      method, followed by single-point MR-CISD calculations. The picture that emerges
      from these calculations is in excellent accord with the experimental findings;
      that is, they explain why some possible products are observed while others are
      not.

PMID- 21954867
TI  - Dimethylaminoborane (H2BNMe2) coordination to late transition metal centers:
      snapshots of the B-H oxidative addition process.
AB  - The reaction of cyclodiborazane [Me(2)N-BH(2)](2) with the chloro(dihydrogen)
      ruthenium complex RuHCl(eta(2)-H(2))(P(i)Pr(3))(2) (1) led to the formation of
      the unsymmetricaly coordinated dimethylaminoborane complex
      RuHCl(H(2)BNMe(2))(P(i)Pr(3))(2) (2). The dimethylaminoborane coordination
      (H(2)BNMe(2)) to the ruthenium center in 2 was carefully studied by combining X
      ray, multinuclear NMR, and density functional theory (DFT) techniques, and
      compared with the recently reported osmium analogue which was originally
      formulated as a sigma-B-H borinium complex [OsH(2)Cl(HBNMe(2))(P(i)Pr(3))(2)]
      (4). All our data are in favor of a bis(sigma-B-H) coordination mode at a very
      activated stage in the case of the ruthenium complex 2, whereas in the osmium
      complex 4, full oxidative addition is favored leading to a complex better
      formulated as an osmium(IV) boryl species with an alpha-agostic B-H interaction.
      The synthesis and characterization of the symmetrical dihydride complex
      RuH(2)(H(2)BNMe(2))(P(i)Pr(3))(2) (3) from addition of the lithium
      dimethylaminoborohydride to 1 is reported for comparison.

PMID- 21954868
TI  - Liposomes composed of unsaturated lipids for membrane modification of human
      erythrocytes.
AB  - Previous studies have shown that certain saturated lipids protect red blood cells
      (RBCs) during hypothermic storage but provide little protection during freezing
      or freeze-drying, whereas various unsaturated lipids destabilize RBCs during
      hypothermic storage but protect during freezing and freeze-drying. The protective
      effect of liposomes has been attributed to membrane modifications. We have
      previously shown that cholesterol exchange and lipid transfer between liposomes
      composed of saturated lipids and RBCs critically depends on the length of the
      lipid acyl chains. In this study the effect of unsaturated lipids with
      differences in their number of unsaturated bonds (18:0/18:1, 18:1/18:1,
      18:2/18:2) on RBC membrane properties has been studied. RBCs were incubated in
      the presence of liposomes and both the liposomal and RBC fraction were analyzed
      by Fourier transform infrared spectroscopy (FTIR) after incubation. The liposomes
      caused an increase in RBC membrane conformational disorder at suprazero
      temperatures. The fluidizing effect of the liposomes on the RBC membranes,
      however, was found to be similar for the different lipids irrespective of their
      unsaturation level. The gel to liquid crystalline phase transition temperature of
      the liposomes increased after incubation with RBCs. RBC membrane fluidity
      increased linearly during the first 8 hours of incubation in the presence of
      liposomes. The increase in RBC membrane fluidity was found to be temperature
      dependent and displayed Arrhenius behaviour between 20 and 40 degrees C, with an
      activation energy of 88 kJ mol-1. Taken together, liposomes composed of
      unsaturated lipids increase RBC membrane conformational disorder, which could
      explain their cryoprotective action.

PMID- 21954869
TI  - Effects of lubricant-mixing time on prolongation of dissolution time and its
      prediction by measuring near infrared spectra from tablets.
AB  - The relationship between lubricant-mixing time and dissolution time was
      investigated, and we established a calibration model to predict dissolution time
      by near infrared (NIR) spectroscopy and the rationale of the prediction. The bulk
      powder consisted of theophylline, lactose, and potato starch were pre-mixed.
      After magnesium stearate (Mg-St) was added, the material was mixed for up to 180
      min. The mixed powders were compressed to tablets and dissolution tests were
      performed. From each dissolution curve, 50% dissolution time (T50) was
      calculated. The NIR spectra of each tablet's upper surface was measured and a
      chemometric analysis was conducted. With the extension of mixing time, T50 was
      prolonged. The Mg-St widely covered the surface of each particle of the bulk
      powder after material mixing. This coating effect may decrease the wettability of
      the particles and cause the prolongation of dissolution time. The T50 was
      predicted by NIR spectroscopy with chemometrics and a calibration model was
      established. The regression vector showed typical peaks derived from -CH group of
      Mg-St, and it is suggested that those peaks, which were caused by the thin layer
      extension of Mg-St particles over the particle surfaces of other materials,
      contributed to the prediction of T50 prolongation. These studies show the
      usefulness of NIR measurements to control the effect of a lubricant in the
      process of raw powder material mixing.

PMID- 21954870
TI  - Recent increase in Nybelinia surmenicola prevalence and intensity in Pacific hake
      (Merluccius productus) off the United States west coast.
AB  - A larval marine cestode was found in 82.0% of 834 Pacific hake (Merluccius
      productus) stomachs collected from 341 trawl stations along the United States
      west coast during the summers of 2008 and 2009. Morphology and DNA sequencing was
      used to identify the cestode as Nybelinia surmenicola. In an examination of 131
      Pacific hake stomachs collected from the same region in 1999, N. surmenicola
      prevalence was 35.1%. The results from a general linear model suggested that
      their prevalence is influenced by year and latitude, Pacific hake size, and sex.
      Mean intensity of N. surmenicola in 2008-2009 was 20.22 (+/-1.13 SE) and was
      positively related to Pacific hake length and the latitude of collection. Year-1
      Pacific hake (<27 cm length) had significantly lower prevalence and intensity of
      N. surmenicola compared to older and larger fish. Pacific hake collected south of
      Point Conception, California (32.5 to 35 degrees N) had lower prevalence and
      intensity of N. surmenicola compared to those collected in northern latitudes
      (35.1 to 48.4 degrees N). Higher N. surmenicola prevalence in Pacific hake in
      recent years suggests food-web fluctuations in the northern California current
      ecosystem caused by changes in ocean transport of zooplankton or pelagic fish
      distributions and warrants future monitoring as a metric for ecosystem change.

PMID- 21954871
TI  - The development of uncertainty monitoring in early childhood.
AB  - This study examined the development of uncertainty monitoring in early childhood.
      Specifically, this study tested the prediction that preschoolers can reflect on
      their sense of certainty about the likely accuracy of their decisions, and it
      examined whether this ability differs across domains. Three-, 4-, and 5-year-olds
      (N = 74) completed a perceptual identification and a lexical identification task
      in which they reported whether they were certain or uncertain about their
      answers. Results showed that even 3-year-olds provided confidence judgments that
      discriminated accurate from inaccurate responses, but this discrimination
      increased with age. Furthermore, results suggest that 3-year-olds primarily rely
      on response latency to assess certainty, whereas older preschoolers do not.
      Overall, these findings suggest that uncertainty monitoring emerges and develops
      during the preschool years.

PMID- 21954872
TI  - The basis for Canada's new low-risk drinking guidelines: a relative risk approach
      to estimating hazardous levels and patterns of alcohol use.
AB  - ISSUE: Low-risk drinking guidelines have been developed independently in a number
      of jurisdictions resulting in different sets of advice with different definitions
      of 'low risk'. This paper discusses some of the fundamental issues addressed by
      an expert advisory panel during the course of developing national guidelines for
      Canadians and summarises key sets of evidence that were influential. APPROACH:
      The underlying reasoning and connection between the evidence and the guidelines
      is discussed in relation to: (i) how to minimise risk of long-term illnesses;
      (ii) how to minimise risk of short-term harms, for example injury; and (iii)
      alcohol use during pregnancy. Both absolute and relative risks were considered in
      the development of the guidelines. FINDINGS: Meta-analyses of all-cause mortality
      were used to identify upper limits for usual drinking levels where potential
      benefits and risks were balanced for the average person in comparison with
      lifetime abstainers (10 standard drinks per week for women, 15 for men).
      Emergency room studies and situational risk factors were considered for advice on
      reducing short-term: (i) when not to drink at all; (ii) how to reduce
      intoxication; and (iii) upper limits for occasional daily consumption by adults
      aged 25 to 64 years (3 standard drinks for women, 4 for men). Shortcomings in the
      research data were highlighted. IMPLICATIONS: It was estimated that total
      compliance with these guidelines at a national level would result in
      substantially reduced per capita alcohol consumption and approximately 4600 fewer
      deaths per year.

PMID- 21954873
TI  - Molecular screening of MECP2 gene in a cohort of Lebanese patients suspected with
      Rett syndrome: report on a mild case with a novel indel mutation.
AB  - BACKGROUND: Rett syndrome (RTT), an X-linked, dominant, neurodevelopment disorder
      represents 10% of female subjects with profound intellectual disability.
      Mutations in the MECP2 gene are responsible for up to 95% of the classical RTT
      cases, and nearly 500 different mutations distributed throughout the gene have
      been reported. METHODS: We report here the molecular study of two isoforms,
      MECP2_e1 and MECP2_e2, in 45 Lebanese girls presenting developmental delay and at
      least one of the following features: microcephaly, neurodegeneration, abnormal
      behaviour, stereotypical hand movements, teeth grinding and difficulty in
      walking. Mutation screening was performed by denaturating high-performance liquid
      chromatography combined with direct sequencing. RESULTS: Sixteen variants were
      noted, of which 14 have been previously reported: five suspected polymorphisms
      and nine mutations. Two variants were novel mutations in exon 4:
      c.1093_1095delGAG (p.E365del) and
      c.1164_1184delACCTCCACCTGAGCCCGAGAGinsCTGAGCCCCAGGACTTGAGCA (p.P388PfsX389). The
      deletion was found in an 8-year-old girl with typical clinical features of RTT.
      The indel was found in a 6-year-old girl with a very mild phenotype. CONCLUSION:
      Genotype/phenotype correlation is discussed and the importance of a molecular
      study of MECP2 gene in patients with very mild features or a regression after the
      age of 2 is raised.

PMID- 21954874
TI  - How mechanical circulatory support helps not to need it--new strategies in
      pediatric heart failure.
AB  - During the past 3 years, seven potential candidates for mechanical circulatory
      support (MCS) were treated at our center. Ultimately, only one of them needed MCS
      (extracorporeal membrane oxygenation [ECMO] for 16 days), although 5 years
      earlier, all would have been considered for MCS at our center. Seven consecutive
      patients were seen in this period: four toddlers (three suffering from fulminant
      myocarditis and one with dilated cardiomyopathy associated with spongy
      myocardium) and three adolescents (two with postmyocarditis cardiomyopathy and
      one with hypertrophic cardiomyopathy and severe restrictive dysfunction after an
      ischemic event with cardiopulmonary resuscitation [stunned heart]). All patients
      presented in acute cardiocirculatory decompensation. All were admitted to the
      intensive care unit (ICU); all but one were sedated and intubated. A combination
      of levosimendan, milrinone, and nesiritide was administered to all patients. Use
      of catecholamines was kept short (<48 h in six individuals). MCS (ECMO, Berlin
      Heart Excor Pediatric, and Heartware) was always available. MCS initiation was
      indicated in only one patient, who was developing progressive multiorgan failure
      (MOF). The three toddlers with myocarditis recovered with complete normalization
      of myocardial function within 6 months. The fourth toddler is still at the ICU
      while waiting for transplantation. The three adolescents were listed with high
      urgency for heart transplantation, and all received a graft within 3 weeks. The
      adolescent with the stunned heart developed progressive MOF and was successfully
      supported with ECMO until transplantation. All six patients with completed course
      were discharged home in New York Heart Association Heart Failure Functional
      Classification System I condition without neurological deficits. Combined use of
      levosimendan, milrinone, and nesiritide, avoidance of catecholamines as much as
      possible, and MCS as backup are the new strategies at our center. This
      cardioprotective approach gives excellent outcome at lower risk and better cost
      effectiveness in our pediatric patients with acute heart failure. Pediatric
      trials are recommended to evaluate combined use of newer cardioprotective drugs.

PMID- 21954875
TI  - beta2-Adrenergic receptor-induced transactivation of epidermal growth factor
      receptor and platelet-derived growth factor receptor via Src kinase promotes rat
      cardiomyocyte survival.
AB  - Chronic stimulation of the beta-AR (adrenergic receptor) promotes apoptosis of
      cardiomyocytes, which is implicated in cardiac dysfunction. beta1-AR and beta2-AR
      are the main subtypes of beta-AR that exert distinct effects on the survival of
      cardiomyocytes. To clarify the physiological roles of beta1-AR and beta2-AR in
      cardiomyocytes, the effects of beta1-AR or beta2-AR knockdown on the survival of
      H9c2 cardiomyocytes was investigated. Knockdown of beta2-AR, but not beta1-AR,
      suppressed the phosphorylation of EGFR (epidermal growth factor receptor) and
      PDGFR (platelet-derived growth factor receptor) induced by ISO (isoprenaline).
      The EGFR inhibitor, AG1478, attenuated ERK (extracellular-signal-regulated
      kinase) activation and partially decreased cell survival. Pretreatment with
      AG1296, a PDGFR inhibitor, abolished ISO-induced Akt (also known as protein
      kinase B) phosphorylation and led to a decrease in cell viability. In addition,
      the Src tyrosine kinase inhibitor, PP2, blocked ISO-mediated both Akt and ERK
      activation and heavily suppressed viability. Accordingly, in primary neonatal rat
      cardiomyocytes, the beta2-AR inhibitor, but not the beta1-AR inhibitor, abrogated
      the transactivation of EGFR and PDGFR, which was respectively related to Akt and
      ERK activation. The results show that beta2-AR transactivates PDGFR and EGFR,
      thereby promoting survival of cardiomyocytes.

PMID- 21954876
TI  - Testing the role of phenotypic plasticity for local adaptation: growth and
      development in time-constrained Rana temporaria populations.
AB  - Phenotypic plasticity can be important for local adaptation, because it enables
      individuals to survive in a novel environment until genetic changes have been
      accumulated by genetic accommodation. By analysing the relationship between
      development rate and growth rate, it can be determined whether plasticity in life
      history traits is caused by changed physiology or behaviour. We extended this to
      examine whether plasticity had been aiding local adaptation, by investigating
      whether the plastic response had been fixed in locally adapted populations.
      Tadpoles from island populations of Rana temporaria, locally adapted to different
      pool-drying regimes, were monitored in a common garden. Individual differences in
      development rate were caused by different foraging efficiency. However,
      developmental plasticity was physiologically mediated by trading off growth
      against development rate. Surprisingly, plasticity has not aided local adaptation
      to time-stressed environments, because local adaptation was not caused by genetic
      assimilation but on selection on the standing genetic variation in development
      time.

PMID- 21954877
TI  - Mechanistic heterogeneity of junctional ectopic tachycardia in adults.
AB  - Spontaneous junctional ectopic tachycardia (JET) in adults is rare, and the
      electrophysiologic mechanism has not been definitively established. Two patients
      who presented with JET, not associated with cardiac surgery, were evaluated and
      studied in the electrophysiology laboratory, and electrophysiologic and
      pharmacologic maneuvers were performed to assess the mechanisms of tachycardia.
      The junctional tachycardia in Patient 1 manifested characteristics consistent
      with a triggered mechanism, and was sensitive to adenosine. The junctional
      tachycardia in Patient 2 manifested characteristics consistent with abnormal
      automaticity, and was insensitive to adenosine. This is a rare clinical example
      of abnormal automaticity. These two cases demonstrate that JET may be due to
      multiple mechanisms, with data consistent with triggered activity and abnormal
      automaticity.

PMID- 21954878
TI  - Differential structural remodeling of the left-atrial posterior wall in patients
      affected by mitral regurgitation with or without persistent atrial fibrillation:
      a morphological and molecular study.
AB  - INTRODUCTION: Atrial fibrillation (AF) in mitral regurgitation (MR) is a complex
      disease where multiple factors may induce left-atrial structural remodeling (SR).
      We explored the differential SR of the left-atrial posterior wall (LAPW) of
      patients affected by MR with or without persistent AF, and the expression of key
      proteins involved in its pathogenesis. METHODS AND RESULTS: Light microscopy of
      LAPW samples from 27 patients with MR and persistent AF (group 1), 33 with MR in
      sinus rhythm (group 2), and 15 autopsy controls (group 3) was used to measure
      myocyte diameter, percentage of myocytolytic myocytes, interstitial fibrosis, and
      capillary density; RT-PCR and Western blotting were used to assess the mRNA and
      protein levels of SOD-1, SOD-2, HO-1, calpain, MMP-2, MMP-9, TIMP-1, TIMP-2, and
      VEGF; immunofluorescence was used to locate these proteins. Myocyte diameter was
      similar in groups 1 and 2, but larger than controls. Compared to group 2, group 1
      had more myocytolytic myocytes (20.8 +/- 5.6% vs 14.7 +/- 4.5%; P < 0.0001),
      increased interstitial fibrosis (10.4 +/- 5.1% vs 7.5 +/- 4.2%; P < 0.05), and
      decreased capillary density (923 +/- 107 No/mm(2) vs 1,040 +/- 100 No/mm(2); P <
      0.0001). All of the proteins were more expressed in groups 1 and 2 than in
      controls. The protein and mRNA levels of SOD-1, SOD-2, MMP-2, and MMP-9 were
      higher in group 1 than in group 2. CONCLUSIONS: The LAPW of MR patients with or
      without AF shows considerable SR. The former has more severe histopathological
      changes and higher levels of proteins involved in SR, thereby reaching a
      threshold beyond which the sinus impulse cannot normally activate atrial
      myocardium.

PMID- 21954879
TI  - Fetal development of deep back muscles in the human thoracic region with a focus
      on transversospinalis muscles and the medial branch of the spinal nerve posterior
      ramus.
AB  - Fetal development of human deep back muscles has not yet been fully described,
      possibly because of the difficulty in identifying muscle bundle directions in
      horizontal sections. Here, we prepared near-frontal sections along the thoracic
      back skin (eight fetuses) as well as horizontal sections (six fetuses) from 14
      mid-term fetuses at 9-15 weeks of gestation. In the deep side of the trapezius
      and rhomboideus muscles, the CD34-positive thoracolumbar fascia was evident even
      at 9 weeks. Desmin-reactivity was strong and homogeneous in the superficial
      muscle fibers in contrast to the spotty expression in the deep fibers. Thus, in
      back muscles, formation of the myotendinous junction may start from the
      superficial muscles and advance to the deep muscles. The fact that developing
      intramuscular tendons were desmin-negative suggested little possibility of a
      secondary change from the muscle fibers to tendons. We found no prospective
      spinalis muscle or its tendinous connections with other muscles. Instead,
      abundant CD68-positive macrophages along the spinous process at 15 weeks
      suggested a change in muscle attachment, an event that may result in a later
      formation of the spinalis muscle. S100-positive intramuscular nerves exhibited
      downward courses from the multifidus longus muscle in the original segment to the
      rotatores brevis muscles in the inferiorly adjacent level. The medial cutaneous
      nerve had already reached the thoracolumbar fascia at 9 weeks, but by 15 weeks
      the nerve could not penetrate the trapezius muscle. Finally, we propose a folded
      myotomal model of the primitive transversospinalis muscle that seems to explain a
      fact that the roofing tile-like configuration of nerve twigs in the semispinalis
      muscle is reversed in the multifidus and rotatores muscles.

PMID- 21954880
TI  - Use of a robotic sampling platform to assess young children's exposure to indoor
      bioaerosols.
AB  - Indoor exposures to allergens, mold spores, and endotoxin have been suggested as
      etiological agents of asthma; therefore, accurate determination of those
      exposures, especially in young children (6-36 months), is important for
      understanding the development of asthma. Because use of personal sampling
      equipment in this population is difficult, and in children <1 year of age
      impossible, we developed a personal sampling surrogate: the Pretoddler Inhalable
      Particulate Environmental Robotic (PIPER) sampler to better estimate their
      exposures. During sampling, PIPER simulates the activity patterns, speed of
      motion, and the height of the breathing zones of young children, and mechanically
      resuspends the deposited dust just as a young child does during running and
      crawling. The concentrations of allergens, mold spores, and endotoxin measured by
      PIPER were compared to those measured using traditional stationary air sampling
      method in 75 homes in central New Jersey, United States. Endotoxin was detected
      in all homes with median concentrations of 1.0 and 0.55 EU/m(3) for PIPER and
      stationary sampler, respectively. The difference in median concentrations
      obtained using the two methods was statistically significant for homes with
      carpeted floors (P = 0.0001) in the heating season. For such homes, the average
      ratio of endotoxin concentration measured by PIPER to the stationary sampler was
      2.96 (95% CI 2.29-3.63). Fungal spores were detected in all homes, with median
      fungal concentrations of 316 and 380 spores/m(3) for PIPER and stationary
      sampler, respectively. For fungi, the difference between the two sampling methods
      was not statistically significant. For both sampling methods, the total airborne
      mold levels were statistically significantly higher in the non-heating season
      than in the heating season. Allergens were detected in ~15% of investigated
      homes. The data indicate that the traditional stationary air-sampling methods may
      substantially underestimate personal exposures to endotoxin, especially due to
      resuspension of dust from carpeted floor surfaces. A personal sampling surrogate,
      such as PIPER, is a feasible approach to estimate personal exposures in young
      children. PIPER should be seriously considered as the sampling platform for
      future exposure studies in young children. PRACTICAL IMPLICATIONS: This study
      investigated potential indoor bioaerosol exposure of young children using a
      Pretoddler Inhalable Particulate Environmental Robotic (PIPER) sampler platform.
      The results show that the traditional stationary air-sampling methods can
      substantially underestimate personal exposures to resuspended material, and that
      a personal sampling surrogate, such as PIPER, offers a feasible surrogate for
      measuring personal inhalation exposures of young children.

PMID- 21954881
TI  - SILACtor: software to enable dynamic SILAC studies.
AB  - Stable isotope labeling by amino acids in cell culture (SILAC) is a versatile
      tool in proteomics that has been used to explore protein turnover on a large
      scale. However, these studies pose a significant undertaking that can be greatly
      simplified through the use of computational tools that automate the data
      analysis. While SILAC technology has enjoyed rapid adoption through the
      availability of several software tools, algorithms do not exist for the automated
      analysis of protein turnover data generated using SILAC technology. Presented
      here is a software tool, SILACtor, designed to trace and compare SILAC-labeled
      peptides across multiple time points. SILACtor is used to profile protein
      turnover rates for more than 500 HeLa cell proteins using a SILAC label-chase
      approach. Additionally, SILACtor contains a method for the automated generation
      of accurate mass and retention time inclusion lists that target peptides of
      interest showing fast or slow turnover rates relative to the other peptides
      observed in the samples. SILACtor enables improved protein turnover studies using
      SILAC technology and also provides a framework for features extensible to
      comparative SILAC analyses and targeted methods.

PMID- 21954882
TI  - Prolyl hydroxylase inhibitors increase the production of vascular endothelial
      growth factor by periodontal fibroblasts.
AB  - BACKGROUND AND OBJECTIVE: Pharmacological inhibitors of prolyl hydroxylases
      (PHDs) can induce a proangiogenic response that favors wound healing and bone
      regeneration. However, the response of periodontal cells to PHD inhibitors is
      unknown. MATERIAL AND METHODS: To determine the effects of PHD inhibitors on
      periodontal cells, we exposed human fibroblasts from the gingiva and the
      periodontal ligament to dimethyloxallyl glycine, desferrioxamine, l-mimosine and
      CoCl(2). Viability, proliferation, and protein synthesis were assessed by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), [(3)H]thymidine, and
      [(3)H]leucine incorporation, respectively. The levels of Ki67, hypoxia-inducible
      factor 1alpha (HIF-1alpha), p27, phosphorylated c-Jun N-terminal kinase (JNK) and
      phosphorylated p38 were determined by immunohistochemistry and western blotting.
      Vascular endothelial growth factor (VEGF) mRNA levels were measured by
      quantitative PCR. Protein levels of VEGF and interleukin (IL)-6 were evaluated by
      immunoassays. RESULTS: We found that PHD inhibitors, while leaving cell viability
      unchanged, reduced proliferation and protein synthesis. This was paralleled by
      decreased Ki67 levels and increased p27 levels, suggesting that PHD inhibitors
      provoke growth arrest. Independently from this response, PHD inhibitors
      stabilized HIF-1alpha and increased the production of VEGF. This increase of VEGF
      was observed in the presence of proinflammatory IL-1 and pharmacological
      inhibitors of JNK and p38 signaling. Moreover, PHD inhibitors did not modulate
      expression of IL-6 and the phosphorylation of JNK and p38. CONCLUSION: These
      results suggest that PHD inhibitors enhance the production of VEGF in periodontal
      fibroblasts, even in the presence of proinflammatory IL-1. The data further
      suggest that PHD inhibitors do not provoke a significant proinflammatory or anti
      inflammatory response in this in vitro setting.

PMID- 21954883
TI  - Effect of Gelsemium 5CH and 15CH on anticipatory anxiety: a phase III, single
      centre, randomized, placebo-controlled study.
AB  - Therapeutics to treat or prevent anxiety are numerous but many people choose to
      try non-conventional medicine such as homeopathy. This study aimed at evaluating
      the effectiveness of Gelsemium 5CH and 15CH on provoked anxiety in healthy
      volunteers, in comparison with placebo. This was a double-blind, single-centre,
      randomized, placebo-controlled study. Eligible healthy men or women aged from 18
      to 40 years without a history of psychiatric disorders were randomly allocated to
      receive Gelsemium 5 or 15CH or placebo. Anxiety was proved by performance of the
      Stroop colour word test (SCWT). The primary end-point was anxiety assessed by the
      State measure of the State-Trait Anxiety Inventory (STAI-S) as the absolute value
      and difference with baseline, according to the treatment received. We included
      180 healthy volunteers. The distribution into each treatment group was
      homogenous. There was no statistical difference between groups for the values of
      STAI-S at baseline, just before the SCWT and the difference between these times
      (1.8 [0.20 to 3.4], 1.0 [-0.6 to 2.6] and 1.4 [-0.3 to 3.0] for Gelsemium 15CH,
      5CH and placebo respectively). Likewise, no statistical difference was observed
      between groups in anxiety as measured by a Visual Analogue Scale and the
      Competitive State Anxiety Inventory. Mean arterial pressure and heart rate
      significantly increased (P < 0.001) but no interaction between time prior to
      provoked anxiety and treatment was shown (P = 0.59 and P = 0.46, respectively).
      Gelsemium 5CH and 15CH do not prevent anticipatory anxiety in the conditions used
      in this study.

PMID- 21954884
TI  - Gestation-specific reference intervals for right and left ventricular ejection
      force from 12 to 40 weeks of gestation.
AB  - AIM: Ejection force of the fetal cardiac ventricles has previously been described
      from 18weeks of gestation. We aimed to establish gestation-specific reference
      intervals for ventricular ejection force (VEF) from 12 to 40weeks of pregnancy.
      MATERIAL AND METHODS: In a cross-sectional observational study of singleton
      pregnancies, examinations were performed in 236 women evenly distributed across
      each week of pregnancy from 12 to 40weeks. Each mother was scanned once. For the
      aortic and pulmonary valves, the time to peak velocity (TPV) and the average
      (TAV) and peak flow velocity in systole (PSV) was measured. For each we averaged
      values from three consecutive complexes. The outlet valve diameters were measured
      and the VEF on both the right and left sides were calculated using the formula
      VEF=(1.055*valve area*time to peak velocity*TAV)*(PSV/TPV) where 1.055 represents
      the density of blood. Measurements were repeated in 40 women to assess
      intraobserver reproducibility and in 19 women for interobserver variability.
      RESULTS: We present reference intervals for right and left VEF. We demonstrated
      that the ventricular force on both right and left sides increases with advancing
      gestational age. CONCLUSION: Fetal cardiac physiology can be studied and Doppler
      indices reliably measured as early as the late first trimester of pregnancy.
      Ventricular ejection force and its relationship with fetal growth could be
      explored in future studies and this may eventually provide better understanding
      of changes which may predispose to adult cardiac disease.

PMID- 21954885
TI  - Glionitrin B, a cancer invasion inhibitory diketopiperazine produced by microbial
      coculture.
AB  - A new diketopiperazine, glionitrin B (1), was produced using a microbial
      coculture of the fungus Aspergillus fumigatus KMC-901 and the bacterium
      Sphingomonas sp. KMK-001 that were isolated from acidic coal mine drainage. The
      structure of 1 was determined to be (3S,10aS)-dithiomethylglionitrin A. This
      structure was determined by the analyses of extensive NMR data and the circular
      dichroism spectra of the natural product and a semisynthetic compound derived
      from glionitrin A. In contrast to glionitrin A (2), glionitrin B (1) is not
      cytotoxic against the human prostate cancer cell line DU145. However, compound 1
      caused suppression of DU145 cell invasion, producing 46% inhibition at 60 MUM.

PMID- 21954886
TI  - Formation of self-assembled chains of tetrathiafulvalene on a Cu(100) surface.
AB  - Formation of self-assembled chains of tetrathiafulvalene (TTF) on the Cu(100)
      surface has been investigated by scanning tunneling microscopy and density
      functional theory calculations that include semiempirical van der Waals (vdW)
      interaction corrections. The calculations show that the chain structures observed
      in the experiments can only be explained by including the vdW interactions. The
      molecules are tilted along the chain in order to achieve maximal intermolecular
      interaction. The chains are metastable on the surface, which is consistent with
      the experimental observation that they disappear after annealing. The fact that
      all TTF chains observed in the experiment are short might be possibly explained
      by the interplay between the stabilizing vdW molecule-molecule interaction and
      the destabilizing rearrangement of surface atoms due to the strong molecule
      substrate interaction.

PMID- 21954887
TI  - Kinetics of enzyme-catalyzed cross-linking of feruloylated arabinan from sugar
      beet.
AB  - Ferulic acid (FA) groups esterified to the arabinan side chains of pectic
      polysaccharides can be oxidatively cross-linked in vitro by horseradish
      peroxidase (HRP) catalysis in the presence of hydrogen peroxide (H(2)O(2)) to
      form ferulic acid dehydrodimers (diFAs). The present work investigated whether
      the kinetics of HRP catalyzed cross-linking of FA esterified to alpha-(1,5)
      linked arabinans are affected by the length of the arabinan chains carrying the
      feruloyl substitutions. The kinetics of the HRP-catalyzed cross-linking of four
      sets of arabinan samples from sugar beet pulp, having different molecular weights
      and hence different degrees of polymerization, were monitored by the
      disappearance of FA absorbance at 316 nm. MALDI-TOF/TOF-MS analysis confirmed
      that the sugar beet arabinans were feruloyl-substituted, and HPLC analysis
      verified that the amounts of diFAs increased when FA levels decreased as a result
      of the enzymatic oxidation treatment with HRP and H(2)O(2). At equimolar levels
      of FA (0.0025-0.05 mM) in the arabinan samples, the initial rates of the HRP
      catalyzed cross-linking of the longer chain arabinans were slower than those of
      the shorter chain arabinans. The lower initial rates may be the result of the
      slower movement of larger molecules coupled with steric phenomena, making the
      required initial reaction of two FAs on longer chain arabinans slower than on
      shorter arabinans.

PMID- 21954889
TI  - FVIII binding to PS membranes differs in the activated and non-activated form and
      can be shielded by annexin A5.
AB  - Binding of Factor VIII to phosphatidylserine (PS)-expressing platelets is a key
      process in the intravascular pathway of the blood coagulation cascade. Activated
      by thrombin, FVIIIa acts as a cofactor on the surface of platelets. It is under
      debate whether and how annexin A5 influences FVIIIa binding to platelets. Here,
      we investigate FVIII binding to PS-containing vesicles as model platelets and its
      interplay with annexin A5 in buffer using fluorescence correlation spectroscopy
      (FCS). We find that activated FVIIIa, in contrast to inactivated FVIII, exhibits
      a striking binding anomaly as a function of PS content, marked by a sharp maximum
      of the binding constant around 11% PS, which is close to the natural PS content
      of platelets. Furthermore, we show that the addition of annexin A5 can both
      increase or decrease this FVIIIa binding depending on whether the relative PS
      content is lower or higher than the maximum binding value. We demonstrate in
      theory that the observed binding diagram supports the hypothesis that annexin
      shields PS, indicating a possible indirect regulatory role of annexin A5 in blood
      coagulation. The overall PS- and annexin-dependent binding behavior of activated
      FVIIIa is preserved in experiments in blood plasma, confirming the validity of
      our results under more physiological conditions.

PMID- 21954890
TI  - Surface-functionalization-dependent optical properties of II-VI semiconductor
      nanocrystals.
AB  - We report a study of the surface-functionalization-dependent optical properties
      of II-VI zinc-blende semiconductor nanocrystals on the basis of ligand-exchange
      chemistry, isomaterial core/shell growth, optical spectroscopy, transmission
      electron microscopy, and X-ray powder diffraction. Our results show that the
      transition energy and extinction coefficient of the 2S(h3/2)1S(e) excitonic band
      of these nanocrystals can be strongly modified by their surface ligands as well
      as ligand associated surface atomic arrangement. The oleylamine exchange of
      oleate-capped zinc-blende II-VI nanocrystals narrows the energy gap between their
      first and second excitonic absorption bands, and this narrowing effect is size
      dependent. The oleylamine exchange results in the quenching, subsequent recovery,
      and even enhancing of the photoluminescence emission of these II-VI semiconductor
      nanocrystals. In addition, the results from our X-ray powder diffraction
      measurements and simulations completely rule out the possibility that oleate
      capped zinc-blende CdSe nanocrystals can undergo zinc-blende-to-wurtzite crystal
      transformation upon ligand exchange with oleylamine. Moreover, our theoretical
      modeling results suggest that the surface-functionalization-dependent optical
      properties of these semiconductor nanocrystals can be caused by a thin type II
      isomaterial shell that is created by the negatively charged ligands (e.g., oleate
      and octadecyl phosphonate). Taking all these results together, we provide the
      unambiguous identification that II-VI semiconductor nanocrystals exhibit surface
      functionalization-dependent excitonic absorption features.

PMID- 21954892
TI  - Hot melt granulation: a facile approach for monolithic osmotic release tablets.
AB  - The aim of this work was to develop and evaluate an extended release matrix
      tablet of glipizide (GP), an oral hypoglycemic agent. Matrices of GP were
      prepared using microcrystalline cellulose Avicel(TM) PH 112, sodium chloride (SC)
      and polyethylene glycol 6000 (PEG). The content of Kollidon SR (KR),
      hydroxypropyl methylcellulose K4M premium CR grade (HM) and polyethylene oxide
      WSR 303 (PO) and/or magnesium hydroxide (MH) was varied in different
      formulations. All the formulations were processed by hot melt granulation
      technique. GP release was observed to be influenced by the amount of SC and MH
      present in the core formulation. The matrix tablets were coated with a solution
      containing combination of cellulose acetate 398.10 (CA) and PEG. The release of
      GP was observed to be inversely proportional to the weight of the coating
      membrane. Matrices containing PO in combination with SC and MH (14.28:8.56)
      showed significantly higher degree of hydration and swelling that was evident in
      the surface texture as visualized by scanning electron microscopy (SEM). Results
      of SEM studies confirmed the presence of pores in the semi-permeable coating
      membrane from where the GP release would have occurred. The release of GP from
      this formulation was similar to that of the marketed extended release tablet as
      judged from similarity factor (f2) analysis, which yielded a value of 74.7. The
      optimized formulation was found to be stable when tested according to long term
      and accelerated storage conditions of ICH guidelines upto 3 months.

PMID- 21954893
TI  - Development and psychometric evaluation of the Treatment Adherence Questionnaire
      for Patients with Hypertension.
AB  - AIM:   This article is a report of the development and psychometric testing of
      the Treatment Adherence Questionnaire for Patients with Hypertension. BACKGROUND:
      Hypertension is the most prevalent health problem among adult patients
      affecting approximately 200 million people in China and about 1 billion persons
      worldwide. Adherence to medication and lifestyle for hypertensive patients result
      in blood pressure control and reduce adverse outcomes. At present, few specific
      adherence instruments are available to completely evaluate medication and
      lifestyle for hypertensive patients. METHODS:   A multi-phase psychometric
      questionnaire development method was used to develop the instrument. The item
      pool was generated using literature review and focus group. Content validity was
      evaluated by expert panel. Then, the field testing was conducted by a convenience
      sampling of 278 hypertensive patients from December 2009 to May 2010 in Guangdong
      Province of China. Exploratory and confirmatory factor analyses were used to test
      construct validity. Finally, internal consistency and test-retest reliability
      were assessed. RESULTS:   The new measure consisted of six dimensions with 28
      items, explaining 62.54% of the total variance in the data. Confirmative factor
      analysis supported a good overall fit of the six-factor model. Cronbach's alpha
      of the overall questionnaire was 0.86 and 0.82 for test-retest reliability.
      CONCLUSIONS:   The questionnaire was a brief and psychometrically sound
      instrument to evaluate hypertensive patients' treatment adherence and to be
      applied in the research and clinical fields.

PMID- 21954895
TI  - Serial prehospital 12-lead electrocardiograms increase identification of ST
      segment elevation myocardial infarction.
AB  - BACKGROUND: Many prehospital protocols require acquisition of a single 12-lead
      electrocardiogram (ECG) when assessing a patient for ST-segment elevation
      myocardial infarction (STEMI). However, it is known that ECG evidence of STEMI
      can evolve over time. OBJECTIVES: To determine how often the first and, if
      necessary, second or third prehospital ECGs identified STEMI, and the time
      intervals associated with acquiring these ECGs and arrival at the emergency
      department (ED). METHODS: We retrospectively analyzed 325 consecutive prehospital
      STEMIs identified between June 2008 and May 2009 in a large third-service
      emergency medical services (EMS) system. If the first ECG did not identify STEMI,
      protocol required a second ECG just before transport and, if necessary, a third
      ECG before entering the receiving ED. Paramedics who identified STEMI at any time
      bypassed participating local EDs, taking patients directly to the percutaneous
      coronary intervention (PCI) center. Paramedics used computerized ECG
      interpretation with STEMI diagnosis defined as an "acute MI" report by
      GE/Marquette 12-SL software in ZOLL E-series defibrillator/cardiac monitors (ZOLL
      Medical, Chelmsford, MA). We recorded the time of each ECG, and the ordinal
      number of the diagnostic ECG. We then determined the number of cases and
      frequency of STEMI diagnosis on the first, second, or third ECG. We also measured
      the interval between ECGs and the interval from the initial positive ECG to
      arrival at the ED. Results. STEMI was identified on the first prehospital ECG in
      275 cases, on the second ECG in 30 cases, and on the third ECG in 20 cases
      (cumulative percentages of 84.6%, 93.8%, and 100%, respectively). For STEMIs
      identified on the second or third ECG, 90% were identified within 25 minutes
      after the first ECG. The median times from identification of STEMI to arrival at
      the ED were 17.5 minutes, 11.0 minutes, and 0.7 minutes for STEMIs identified on
      the first, second, and third ECGs, respectively. CONCLUSIONS: A single
      prehospital ECG would have identified only 84.6% of STEMI patients. This suggests
      caution using a single prehospital ECG to rule out STEMI. Three serial ECGs
      acquired over 25 minutes is feasible and may be valuable in maximizing
      prehospital diagnostic yield, particularly where emergent access to PCI exists.

PMID- 21954894
TI  - Identification of a single light atom within a multinuclear metal cluster using
      valence-to-core X-ray emission spectroscopy.
AB  - Iron valence-to-core Fe Kbeta X-ray emission spectroscopy (V2C XES) is
      established as a means to identify light atoms (C, N, O) within complex
      multimetallic frameworks. The ability to distinguish light atoms, particularly in
      the presence of heavier atoms, is a well-known limitation of both crystallography
      and EXAFS. Using the sensitivity of V2C XES to the ionization potential of the
      bound ligand, energetic shifts of ~10 eV in the ligand 2s ionization energies of
      bound C, N, and O may be observed. As V2C XES is a high-energy X-ray method, it
      is readily applicable to samples in any physical form. This method thus has great
      potential for application to multimetallic inorganic frameworks involved in both
      small molecule storage and activation.

PMID- 21954896
TI  - Critical consciousness development and political participation among marginalized
      youth.
AB  - Given associations between critical consciousness and positive developmental
      outcomes, and given racial, socioeconomic, and generational disparities in
      political participation, this article examined contextual antecedents of critical
      consciousness (composed of sociopolitical control and social action) and its
      consequences for 665 marginalized youth's (ages 15-25) voting behavior. A
      multiple indicator and multiple causes (MIMIC) model examined racial, ethnic, and
      age differences in the measurement and means of latent constructs. The structural
      model suggested that parental and peer sociopolitical support predicts
      sociopolitical control and social action, which in turn predicts voting behavior,
      while controlling for civic and political knowledge, race/ethnicity, and age.
      This illuminates how micro-level actors foster critical consciousness and how the
      perceived capacity to effect social change and social action participation may
      redress voting disparities.

PMID- 21954897
TI  - Intravenous epinephrine infusion test in diagnosis of catecholaminergic
      polymorphic ventricular tachycardia.
AB  - INTRODUCTION: A test involving intravenous infusion of epinephrine has been
      proposed as a method alternative to exercise stress test in diagnosis of
      catecholaminergic polymorphic ventricular tachycardia (CPVT). We aimed at
      estimating the predictive value of intravenous epinephrine administration in CPVT
      patients with frequent exercise-induced ventricular ectopy. METHODS AND RESULTS:
      We recruited 81 subjects, including 25 CPVT-linked ryanodine receptor 2 (RYR2)
      mutation carriers, 11 genetically undefined CPVT patients, and 45 unaffected
      family members. All subjects underwent a maximal exercise stress test and an
      intravenous epinephrine infusion test. Exercise stress test was positive in 25
      (31%) patients including 14 of 25 (56%) established RYR2-mutation carriers and
      all 11 (100%) genetically undefined CPVT patients. Epinephrine infusion induced
      arrhythmias in 3 (12%) RYR2-mutation carriers, 4 (36%) genetically undefined CPVT
      patients, and 1 (2%) unaffected family member. A total of 18 exercise stress test
      positive patients did not respond to intravenous epinephrine administration,
      whereas only 1 epinephrine test responder had a normal exercise stress test.
      Thus, if exercise stress test is used as a standard, the sensitivity of the
      epinephrine infusion test is 28% and specificity is 98%. CONCLUSIONS: Intravenous
      epinephrine infusion has low sensitivity and may not be considered as an
      alternative method for a maximal exercise stress test in diagnosis of CPVT.

PMID- 21954898
TI  - What place, if any, does information on putative cardioprotective effects of
      moderate alcohol use have in safer drinking guidelines?
AB  - INTRODUCTION AND AIMS: The majority view among alcohol epidemiologists is that
      the lower coronary heart disease mortality observed in moderate drinkers is
      probably evidence for a protective effect of moderate drinking. In this paper I
      critically discuss the debate about what type of information, if any, should be
      provided to the public about the putative coronary heart disease benefits of
      moderate alcohol use. RESULTS: Most opposition to informing the public about
      these putative benefits is based on the fear that such advice will increase per
      capita alcohol consumption and therefore alcohol-related harm. It is unclear how
      well-based these concerns are. In the interim, the alcohol industry has
      communicated these putative benefits to the public. CONCLUSIONS: There is a case
      for including some information on these putative benefits in specific safer
      drinking guidelines for middle-aged and older drinkers that: clearly conveys the
      remaining uncertainty about the benefits of moderate drinking, emphasises the
      conditional nature of any such benefits, and stresses the need to balance the
      potential benefits against the increased sensitivity of older adults to other
      adverse effects of alcohol, and the increased risk of interactions between
      alcohol and other medications used by older adults.

PMID- 21954899
TI  - A new method for the determination of vaporization enthalpies of ionic liquids at
      low temperatures.
AB  - A new method for the determination of vaporization enthalpies of extremely low
      volatile ILs has been developed using a newly constructed quartz crystal
      microbalance (QCM) vacuum setup. Because of the very high sensitivity of the QCM
      it has been possible to reduce the average temperature of the vaporization
      studies by approximately 100 K in comparison to other conventional techniques.
      The physical basis of the evaluation procedure has been developed and test
      measurements have been performed with the common ionic liquid 1-ethyl-3
      methylimidazolium bis(trifluoromethanesulfonyl)imide [C(2)mim][NTf(2)] extending
      the range of measuring vaporization enthalpies down to 363 K. The results
      obtained for [C(2)mim][NTf(2)] have been tested for thermodynamic consistency by
      comparison with data already available at higher temperatures. Comparison of the
      temperature-dependent vaporization enthalpy data taken from the literature show
      only acceptable agreement with the heat capacity difference of -40 J K(-1) mol(
      1). The method developed in this work opens also a new way to obtain reliable
      values of vaporization enthalpies of thermally unstable ionic liquids.

PMID- 21954901
TI  - Observing signs of pain in relation to self-injurious behaviour among individuals
      with intellectual and developmental disabilities.
AB  - BACKGROUND: Self-injurious behaviour is a chronic condition among people with
      intellectual and developmental disabilities for which there is no known cure. The
      pain hypothesis suggests that individuals who engage in self-injury have altered
      or diminished pain perception. The purpose of the present study was to assess how
      frequently individuals diagnosed with an intellectual and developmental
      disability who engage in chronic self-injury displayed non-verbal signs of pain
      in relation to their self-injury. METHODS: We videotaped four participants (aged
      28-50 years) in their homes during times when they were likely to engage in self
      injury. Using continuous recording measures, we coded videotapes for the
      frequency and duration of self-injury and expressions of non-verbal pain-related
      behaviours. Sequential analyses were conducted to identify temporal relations
      between pain-related behaviours and self-injury. RESULTS: Our data suggest that
      the existing measures of pain may be systematically related to instances of self
      injury. The relationships, however, appear to vary depending on the person who
      engages in self-injury, the environmental contexts in which the self-injury
      occurs, and perhaps, the type of self-injury in which the person engages.
      CONCLUSIONS: These results support some of the findings of Symons et al. and they
      raise questions about the blunted nociception hypothesis of self-injury.

PMID- 21954900
TI  - A general protease digestion procedure for optimal protein sequence coverage and
      post-translational modifications analysis of recombinant glycoproteins:
      application to the characterization of human lysyl oxidase-like 2 glycosylation.
AB  - Using recombinant DNA technology for expression of protein therapeutics is a
      maturing field of pharmaceutical research and development. As recombinant
      proteins are increasingly utilized as biotherapeutics, improved methodologies
      ensuring the characterization of post-translational modifications (PTMs) are
      needed. Typically, proteins prepared for PTM analysis are proteolytically
      digested and analyzed by mass spectrometry. To ensure full coverage of the PTMs
      on a given protein, one must obtain complete sequence coverage of the protein,
      which is often quite challenging. The objective of the research described here is
      to design a protocol that maximizes protein sequence coverage and enables
      detection of post-translational modifications, specifically N-linked
      glycosylation. To achieve this objective, a highly efficient proteolytic digest
      protocol using trypsin was designed by comparing the relative merits of
      denaturing agents (urea and Rapigest SF), reducing agents [dithiothreitol (DTT)
      and tris(2-carboxyethyl)phophine (TCEP)], and various concentrations of
      alkylating agent [iodoacetamide (IAM)]. After analysis of human apo-transferrin
      using various protease digestion protocols, ideal conditions were determined to
      contain 6 M urea for denaturation, 5 mM TCEP for reduction, 10 mM IAM for
      alkylation, and 10 mM DTT, to quench excess IAM before the addition of trypsin.
      This method was successfully applied to a novel recombinant protein, human lysyl
      oxidase-like 2. Furthermore, the glycosylation PTMs were readily detected at two
      glycosylation sites in the protein. These digestion conditions were specifically
      designed for PTM analysis of recombinant proteins and biotherapeutics, and the
      work described herein fills an unmet need in the growing field of
      biopharmaceutical analysis.

PMID- 21954902
TI  - Nanostructure-based drug delivery systems for brain targeting.
AB  - CONTEXT: It is well-known fact that blood brain barrier (BBB) hinders the
      penetrance and access of many pharmacotherapeutic agents to central nervous
      system (CNS). Many diseases of the CNS remain undertreated and the inability to
      treat most CNS disorders is not due to the lack of effective CNS drug discovery,
      rather, it is due to the ineffective CNS delivery. Therefore, a number of
      nanostructured drug delivery carriers have been developed and explored over the
      past couple of years to transport the drugs to brain. OBJECTIVE: The present
      review will give comprehensive details of extensive research being done in field
      of nanostructured carriers to transport the drugs through the BBB in a safe and
      effective manner. METHODS: The method includes both the polymeric- and lipid
      based nanocarriers with emphasis on their utility, methodology, advantages, and
      the drugs which have been worked on using a particular approach to provide a
      noninvasive method to improve the drug transport through BBB. RESULTS: Polymeric-
      and lipid-based nanocarriers enter brain capillaries before reaching the surface
      of the brain microvascular endothelial cells without the disruption of BBB. These
      systems are further modified with specific ligands vectors and pegylation aiming
      to target and enhance their binding with surface receptors of the specific
      tissues inside brain and increase long circulatory time which favors interaction
      and penetration into brain endothelial cells. CONCLUSION: This review would give
      an insight to the researchers working on neurodegenerative and non
      neurodegenerative diseases of the CNS including brain tumor.

PMID- 21954903
TI  - Cobalt-catalyzed, room-temperature addition of aromatic imines to alkynes via
      directed C-H bond activation.
AB  - A quaternary catalytic system consisting of a cobalt salt, a triarylphosphine
      ligand, a Grignard reagent, and pyridine has been developed for chelation
      assisted C-H bond activation of an aromatic imine, followed by insertion of an
      unactivated internal alkyne that occurs at ambient temperature. The reaction not
      only tolerates potentially senstitive functional groups (e.g., Cl, Br, CN, and
      tertiary amide), but also displays a unique regioselectivity. Thus, the presence
      of substituents such as methoxy, halogen, and cyano groups at the meta-position
      of the imino group led to selective C-C bond formation at the more sterically
      hindered ortho positions. Under acidic conditions, the hydroarylation products of
      dialkyl- and alkylarylacetylenes underwent cyclization to afford benzofulvene
      derivatives, while those of diarylacetylenes afforded the corresponding ketones
      in moderate to good yields. A mechanistic investigation into the reaction with
      the aid of deuterium-labeling experiments and kinetic analysis has indicated that
      oxidative addition of the ortho C-H bond is the rate-limiting step of the
      reaction. The kinetic analysis has also shed light on the complexity of the
      quaternary catalytic system.

PMID- 21954904
TI  - Reduction in maternal complement levels during delivery by cesarean section.
AB  - AIM: Primary elective cesarean sections are being carried out in considerable
      numbers in both developed and developing countries; however, little information
      is available concerning differences in maternal physiological responses
      associated with the mode of delivery. The aim of the present study was to compare
      the changes in the maternal complement and contact systems between delivery by
      cesarean section and vaginal delivery at term. METHODS: Maternal levels of
      complement 3 (C3), complement 4 (C4) and coagulation factor XII (FXII) were
      measured during primary elective cesarean (n=70) and vaginal (n=140) deliveries.
      RESULTS: The C3, C4 and FXII levels decreased significantly during delivery by
      cesarean section and remained low for two hours. By contrast, C3 levels, but not
      C4 levels, increased temporally during normal term delivery and FXII levels
      decreased two hours later. CONCLUSIONS: The changes in maternal C3, C4 and FXII
      levels during cesarean section were very different from those during delivery at
      term, suggesting that the maternal complement and contact systems respond
      differently.

PMID- 21954905
TI  - Generalized lichen nitidus in a Japanese girl.

PMID- 21954906
TI  - Digestibility for dogs and cats of meat and bone meal processed at two different
      temperature and pressure levels*.
AB  - This study evaluated the effect of two rendering processes applied to meat and
      bone meal (MBM) production, associated or not with extrusion, by measuring diet
      apparent total tract digestibility of dogs and cats, and true digestibility of
      amino acids (AA) by cecectomized roosters. Four diets were evaluated, with the
      main protein source as follows: conventional and extruded MBM; high temperature
      and pressure (HPT; 135  degrees C, 3 bar, 20 min) and extruded MBM; conventional
      non-extruded MBM; HPT non-extruded MBM. Nutrient digestibility and food
      metabolizable energy content were evaluated with dogs and cats by the method of
      total collection of faeces. True AA digestibility was evaluated by a precision
      fed assay with cecectomized roosters. The evaluated MBM had high-ash content. The
      HPT process of MBM increased the digestibility of crude protein of the diets by
      cats, and the true digestibility of several AA by cecectomized roosters. The
      extrusion process did not modify the apparent total tract nutrient digestibility
      of MBM by dogs and their amino acid digestibility by roosters, but increased the
      digestibility of the dietary protein by cats. Dogs fed HPT MBM presented a higher
      urea post-prandial response, suggesting reductions in bioavailability and protein
      synthesis from absorbed AA.

PMID- 21954907
TI  - Multi-component regio- and diastereoselective cobalt-catalyzed
      hydrovinylation/allylboration reaction sequence.
AB  - The combination of a regioselective cobalt-catalyzed 1,4-hydrovinylation and the
      diastereoselective allylboronation reaction leads to a wide scope of
      functionalized hydroxydienyl esters in a one-pot reaction in excellent yields.
      With catalytic amounts of base, these products are easily converted either into
      alpha,beta,gamma,delta-unsaturated hydroxyl esters or complex tetrasubstituted
      tetrahydropyrans in chemo- and diastereoselective fashions. In addition, a high
      yielding four-component one-pot reaction involving an acrylate, two different and
      unsymmetrical 1,3-dienes, and an unsaturated aldehyde is presented.

PMID- 21954908
TI  - Comparison of family and therapist perceptions of physical and occupational
      therapy services provided to young children with cerebral palsy.
AB  - ABSTRACT   The purpose of this study was to determine whether parents and
      therapists have similar perceptions of therapy services provided to young
      children with cerebral palsy (CP), reflecting collaboration and provision of
      family-centered care. Forty-six parents of young children with CP and 40
      therapists providing services for those children participated. Parents and
      therapists independently completed the same Services Questionnaire, indicating
      their perceptions of the focus and extent of the children's therapy services. For
      data analysis, answers to survey questions were combined into seven categories of
      items with a similar focus. The Spearman rho correlations and Wilcoxon signed
      rank tests were used to explore relationships and differences between the ratings
      of parents and therapists. No significant correlations were found for the seven
      categories. Significant differences between ratings for five of the seven
      categories were identified, indicating parents and therapists differed in their
      ratings of the focus of therapy interventions. Based on the findings, suggestions
      for improvement in the provision of family-centered care are provided.

PMID- 21954909
TI  - Repetitive irregular narrow and wide-complex tachycardia: what is the mechanism?

PMID- 21954911
TI  - Gait changes with walking devices in persons with Parkinson's disease.
AB  - PURPOSE: To study immediate gait changes in persons with PD when walking with
      different assistive walking devices. METHODS: Ten individuals with idiopathic PD
      participated in the study. Gait parameters were recorded while walking with a
      cane and a wheeled walker, and were compared to a free walk without a walking
      device. RESULTS: Persons with PD walked with slower gait speed when using a cane
      and a wheeled walker compared to walking without any device (p = 0.007, p =
      0.002, respectively). Stride length reduced significantly when walking with a
      wheeled walker (p = 0.001). Walking with the assistive devices did not affect
      cadence, double support phase, heel to heel base of support, stride time, and
      stance period. CONCLUSION: Persons with PD immediately walked with slower gait
      speed when using either a cane or a wheeled walker, and with shorter stride
      length when walking with a wheeled walker. The results may lead to more cautious
      clinical practice in gait rehabilitation using ambulatory assisted devices.

PMID- 21954910
TI  - Development of bifunctional stilbene derivatives for targeting and modulating
      metal-amyloid-beta species.
AB  - Amyloid-beta (Abeta) peptides and their metal-associated aggregated states have
      been implicated in the pathogenesis of Alzheimer's disease (AD). Although the
      etiology of AD remains uncertain, understanding the role of metal-Abeta species
      could provide insights into the onset and development of the disease. To unravel
      this, bifunctional small molecules that can specifically target and modulate
      metal-Abeta species have been developed, which could serve as suitable chemical
      tools for investigating metal-Abeta-associated events in AD. Through a rational
      structure-based design principle involving the incorporation of a metal binding
      site into the structure of an Abeta interacting molecule, we devised stilbene
      derivatives (L1-a and L1-b) and demonstrated their reactivity toward metal-Abeta
      species. In particular, the dual functions of compounds with different structural
      features (e.g., with or without a dimethylamino group) were explored by UV-vis, X
      ray crystallography, high-resolution 2D NMR, and docking studies. Enhanced
      bifunctionality of compounds provided greater effects on metal-induced Abeta
      aggregation and neurotoxicity in vitro and in living cells. Mechanistic
      investigations of the reaction of L1-a and L1-b with Zn(2+)-Abeta species by UV
      vis and 2D NMR suggest that metal chelation with ligand and/or metal-ligand
      interaction with the Abeta peptide may be driving factors for the observed
      modulation of metal-Abeta aggregation pathways. Overall, the studies presented
      herein demonstrate the importance of a structure-interaction-reactivity
      relationship for designing small molecules to target metal-Abeta species allowing
      for the modulation of metal-induced Abeta reactivity and neurotoxicity.

PMID- 21954912
TI  - Tirucallane-type triterpenoids from Dysoxylum lenticellatum.
AB  - Ten new tirucallane-type triterpenoids, represented by a rearranged skeleton
      dysolenticin A (1), dysolenticin B (2), a rare trinortriterpenoid dysolenticin C
      (3), three tirucallane triterpenoid derivatives with a hemiketal moiety
      dysolenticins D-F (4-6), dysolenticins G-I (7, 9, 10), and the new alkaloid
      dysolenticin J (12), together with seven known analogues were isolated from the
      twigs and leaves of Dysoxylum lenticellatum. Their structures were elucidated by
      extensive spectroscopic methods, and those of compounds 1, 3, 4, 6, and 10 were
      confirmed by single-crystal X-ray diffraction experiments. Dysolenticin J (12)
      showed significant vasodilative effects on intact rat aortic rings with a
      diastolic degree of 87.4% at 10 MUg/mL.

PMID- 21954913
TI  - Apple peel polyphenol extract protects against indomethacin-induced damage in
      Caco-2 cells by preventing mitochondrial complex I inhibition.
AB  - The aim of this work was to investigate the role of mitochondrial dysfunction in
      the development of oxidative stress and cytotoxicity induced by indomethacin and
      to evaluate the potential of an apple peel polyphenol extract (APPE) in
      protecting against these events. Indomethacin induced, time-dependently,
      mitochondrial and oxidative perturbations which led to cell losses. An inhibition
      of complex I activity, shown for first time here, which resulted in a concomitant
      drop in cellular ATP and an increment in mitochondrial superoxide production, was
      observed after 10 min of exposure. These early cytotoxicity-triggering events
      were followed by an increase in the intracellular production of superoxide (20
      min), an elevation in the activity of xanthine oxidase which led to an increased
      lipid peroxidation (30 min), and a decline in cell viability which manifested
      after 40 min. These events were selectively prevented using allopurinol, tempol
      and APPE (a standardized apple peel polyphenol extract). While the oxidative and
      cell lytic effects of indomethacin were equally prevented by the three agents,
      only APPE protected against complex I inhibition and its downstream oxidative
      consequences. Since tempol (a SOD mimetic) prevented the elevation in xanthine
      oxidase activity, and allopurinol (a xanthine oxidase inhibitor) totally
      abolished the increment in lipid peroxidation and loss of cell viability, it
      appears that a superoxide-dependent increase in xanthine oxidase activity is
      critical to trigger cytotoxicity. Thus, preventing the early increment in
      superoxide formation that, as a result of inhibiting complex I, takes place
      within mitochondria would be key toward protecting the cells against the
      oxidative and cytolytic effects of indomethacin. The ability of APPE in
      preventing the inhibition of complex I and the subsequent superoxide-dependent
      increase in XO activity warrants further studies to evaluate the mechanism
      involves in the protecting effect of APPE against the indomethacin-associated
      adverse effects in vivo.

PMID- 21954914
TI  - An unusual barrier to gene flow: perpetually immature larvae from inter
      population crosses in the flour beetle, Tribolium castaneum.
AB  - We genetically characterize an unusual hybrid incompatibility phenotype manifest
      in F(1)  offspring of crosses between two populations of Tribolium castaneum.
      Hybrid larvae cease development at the third larval instar, persisting as
      'perpetually immature larvae' thereafter. Although unable to produce viable adult
      hybrid offspring with one another, each population produces abundant, fertile
      hybrids with other populations, indicating a recent origin of the incompatibility
      and facilitating genetic studies. We mapped the paternal component of the hybrid
      phenotype to a single region, which exhibits two characteristics common to hybrid
      incompatibility: marker transmission ratio distortion within crosses and elevated
      genetic divergence between populations. The incompatible variation and an
      elevation in between-population genetic divergence is associated with a region
      containing the T. castaneum ecdysone receptor homologue, a major regulatory
      switch, controlling larval moults, pupation and metamorphosis. This contributes
      to understanding the genetics of speciation in the Coleoptera, one of the most
      speciose of all arthropod taxa.

PMID- 21954915
TI  - Effects of acetate-free citrate-containing dialysate on metabolic acidosis,
      anemia, and malnutrition in hemodialysis patients.
AB  - Previously, dialysate contained small amounts of acetate as an alkaline buffer.
      Recently, acetate-free dialysate (A[-]D) has been available. We evaluated the
      clinical effect of A(-)D over acetate-containing dialysate (A(+)D) on acid-base
      balance, anemia, and nutritional status in maintenance hemodialysis (MHD)
      patients. Twenty-nine patients on MHD were treated with A(+)D for 4 months (first
      A(+)D), switched to A(-)D for 4 months, and returned to A(+)D for the next 4
      month period (second A(+)D). Metabolic acidosis: Serum bicarbonate (HCO3(-) )
      levels did not change in patients with normal HCO3(-)  levels (>=20 mEq/L)
      throughout the study. Meanwhile, in patients with initially low HCO3(-)  levels,
      it was significantly increased during the A(-)D period only. Anemia: In patients
      with target hemoglobin (Hb) >=10 g/dL, Hb levels were maintained during the study
      period, even if the dose of erythropoiesis-stimulating agents (ESAs) decreased.
      In patients with low Hb levels, it was significantly increased in the A(-)D
      period without increasing ESA or iron doses. Nutritional Condition: In patients
      with normal albumin levels (>=3.8 g/dL), albumin did not change throughout the
      study period. However, in patients with lower albumin levels, it was
      significantly increased during the A(-)D period. These improvements in metabolic
      acidosis, anemia, and nutrition in the A(-)D period completely dissipated during
      the second A(+)D period. Hemodialysis (HD) with A(-)D may improve a patient's
      clinical status with intractable metabolic acidosis, hyporesponsiveness to ESA,
      and malnutrition that were not normalized in HD with A(+)D.

PMID- 21954916
TI  - Variants of the human NR1I2 (PXR) locus in chronic periodontitis.
AB  - BACKGROUND AND OBJECTIVE: Recent studies on genetic variants of the pregnane X
      receptor (PXR) revealed associations with the mucosal immune response. This study
      aimed to investigate the potential association of functional polymorphisms of the
      NR1I2 (PXR)-encoding gene (rs12721602, rs3814055, rs1523128, rs1523127,
      rs45610735, rs6785049, rs2276707 and rs3814057) with chronic periodontitis.
      MATERIAL AND METHODS: At total of 402 periodontitis patients and 793 healthy
      individuals were genotyped using PCR and melting-curve analysis. RESULTS:
      Frequency distribution of genotypes for the eight single nucleotide polymorphisms
      showed no significant difference between patients with periodontitis and
      controls. Among the eight tested polymorphisms, two blocks were defined showing
      complete or almost complete linkage disequilibrium (linkage disequilibrium block
      1: rs3814055 and rs1523127; and linkage disequilibrium block 2: rs6785049,
      rs2276707 and rs3814057). For one haplotype (GTGAG) composed of rs12721602,
      rs3814055, rs1523128, rs12721607 and rs6785049, a significant association with
      periodontitis was found [p-value after permutation with 100,000 iterations
      (p(permut.)) = 0.011, odds ratio = 0.46, 95% confidence interval: 0.25-0.84)
      following adjustment for age, gender and smoking. CONCLUSION: A rare haplotype of
      the NR1I2 (PXR) locus was associated with the individual susceptibility for
      chronic periodontitis in a German cohort. As a result of the borderline
      significance and the small effect size the present results need further
      confirmation.

PMID- 21954917
TI  - Haem oxygenase-1 counteracts the effects of interleukin-1beta on inflammatory and
      senescence markers in cartilage-subchondral bone explants from osteoarthritic
      patients.
AB  - IL (interleukin)-1beta plays an important role in cartilage extracellular matrix
      degradation and bone resorption in OA (osteoarthritis) through the induction of
      degradative enzymes and pro-inflammatory mediators. In the present study, we have
      determined the consequences of HO-1 (haem oxygenase-1) induction on markers of
      inflammation and senescence in the functional unit cartilage-subchondral bone
      stimulated with IL-1beta. Cartilage-subchondral bone specimens were obtained from
      the knees of osteoarthritic patients. Treatment with the HO-1 inducer CoPP
      (cobalt protoporphyrin IX) counteracted the stimulatory effects of IL-1beta on IL
      6, nitrite, PGE2 (prostaglandin E2), TGF (transforming growth factor) beta2,
      TGFbeta3 and osteocalcin. Immunohistochemical analyses indicated that CoPP
      treatment of explants down-regulated iNOS (inducible nitric oxide synthase), COX
      2 (cyclooxygenase-2) and mPGES-1 (microsomal prostaglandin E synthase-1) induced
      by IL-1beta. In contrast, the expression of HMGB1 (high-mobility group box 1) was
      not significantly modified. In addition, CoPP decreased the expression of iNOS
      and mPGES-1 in cells isolated from the explants and stimulated with IL-1beta,
      which was counteracted by an siRNA (small interfering RNA) specific for human HO
      1. In isolated primary chondrocytes, we determined senescence-associated beta
      galactosidase activity and the expression of senescence markers by real-time PCR.
      We have found that HO-1 induction could regulate senescence markers in the
      presence of IL-1beta and significantly affected telomerase expression, as well as
      beta-galactosidase activity and hTERT (human telomerase reverse transcriptase)
      and p21 expression in chondrocytes. The findings of the present study support the
      view that HO-1 induction results in the down-regulation of inflammatory and
      senescence responses in OA articular tissues.

PMID- 21954918
TI  - Territory quality determines social group composition in Ethiopian wolves Canis
      simensis.
AB  - 1. We contrast the value of four different models to predict variation in
      territory size as follows: resource density (the ideal free distribution),
      population density, group size and intruder pressure (relative resource-holding
      potential). In the framework of the resource dispersion hypothesis, we test the
      effect of resource abundance and spatial variation in resource distribution on
      the age/sex composition of social groups. 2. We explore these drivers of
      territory size and group size/composition in Ethiopian wolves Canis simensis in
      the Bale Mountains, Ethiopia, using fine-scale distribution maps of their major
      prey species based on satellite-derived vegetation maps. 3. The number of adult
      males is correlated with territory size, while prey density, wolf population
      density and intruder pressure are not associated with territory size. On average,
      each additional adult male increases territory size by 1.18 km(2). 4. Prey
      abundance increases with territory size (average biomass accumulation of 6.5 kg
      km(-2)), and larger territories provide greater per capita access to prime
      foraging habitat and prey. 5. The age/sex composition of wolf packs is more
      closely related to territory quality than territory size. Subordinate adult
      females are more likely to be present in territories with greater proportions of
      prime giant molerat Tachyoryctes macrocephalus habitat (i.e. >80% of Web Valley
      territories and >20% in Sanetti/Morebawa), and more yearlings (aged 12-23 months)
      occur in territories with greater overall prey biomass. 6. Wolf packs with
      restricted access to good foraging habitat tend to defend more exclusive
      territories, having a lower degree of overlap with neighbouring packs. 7. The
      greater per capita access to prey in large groups suggests a strong evolutionary
      advantage of collaborative territorial defence in this species, although the
      relative costs of territorial expansion vs. exclusion depend upon the spatial
      distribution of resources. We propose a model whereby territory size is
      determined by the number of adult males, with the presence of subordinate females
      and yearlings dependent on the quality of habitat, and the abundance and
      distribution of prey, incorporated within territory boundaries.

PMID- 21954920
TI  - Characterization of CF4/CF3Br binary mixture adsorption on
      hydrophobic/hydrophilic surfaces via atomistic MD simulation.
AB  - Molecular dynamics simulations of multilayer adsorption of binary mixtures of two
      tetrasubstituted halomethanes (CF(4) and CF(3)Br) on two very different
      substrates (graphite vs hydroxylated SiO(2)) were performed for three different
      bulk compositions (40%, 50%, and 60% CF(4)) and over a range of temperatures from
      80 to 200 K. The goal of these simulations was to investigate in depth how these
      factors affect film structure, layer composition, lateral arrangement, and
      molecular orientation in the first adsorbed layer on each substrate. In line with
      a previous study of single-component adsorption on these surfaces, mixtures
      adsorbed on the hydroxylated SiO(2) surface show stable number density profiles
      that are largely independent of temperature, up to 160 K. This level of stability
      is essentially absent in the case of adsorption on graphite, which show densities
      and surface populations that are largely dependent on overall film composition,
      molecular orientation, and adsorbate-substrate interactions, in addition to
      system temperature. Further, the composition of the first adsorbed layer at each
      solid surface appears to be influenced by the choice of substrate, with CF(3)Br
      the majority component at the graphite surface for all compositions and
      temperatures, while the first adsorbed layer on hydroxylated SiO(2) more clearly
      mirrors the overall film composition at temperatures below 160 K.

PMID- 21954919
TI  - The moderating capacity of racial identity between perceived discrimination and
      psychological well-being over time among African American youth.
AB  - This study examined the influence of racial identity in the longitudinal relation
      between perceptions of racial discrimination and psychological well-being for
      approximately 560 African American youth. Latent curve modeling (LCM) and
      parallel process multiple-indicator LCMs with latent moderators were used to
      assess whether perceptions of racial discrimination predicted the intercept
      (initial levels) and the slope (rate of change) of psychological well-being over
      time, and whether racial identity moderates these relations. The results
      indicated that African American adolescents who reported higher psychological
      responses to discrimination frequency levels at the first time point had lower
      initial levels of well-being. Regressing the slope factor for psychological well
      being on the frequency of discrimination also revealed a nonsignificant result
      for subsequent well-being levels.

PMID- 21954921
TI  - The association between exposure to point-of-sale anti-smoking warnings and
      smokers' interest in quitting and quit attempts: findings from the International
      Tobacco Control Four Country Survey.
AB  - AIMS: This study aimed to examine the associations between reported exposure to
      anti-smoking warnings at the point-of-sale (POS) and smokers' interest in
      quitting and their subsequent quit attempts by comparing reactions in Australia
      where warnings are prominent to smokers in other countries. DESIGN: A prospective
      multi-country cohort design was employed. SETTING: Australia, Canada, the United
      Kingdom and the United States. PARTICIPANTS: A total of 21,613 adult smokers who
      completed at least one of the seven waves (2002-08) of the International Tobacco
      Control Four Country Survey were included in the analysis. MEASUREMENTS: Reported
      exposure to POS anti-smoking warnings and smokers' interest in quitting at the
      same wave and quit attempts over the following year. FINDINGS: Compared to
      smokers in Canada, the United Kingdom and the United States, Australian smokers
      reported higher levels of awareness of POS anti-smoking warnings, and this
      difference was consistent over the study period. Over waves in Australia (but not
      in the other three countries) there was a significantly positive association
      between reported exposure to POS anti-smoking warnings and interest in quitting
      [adjusted odds ratio = 1.139, 95% confidence interval (CI) 1.039-1.249, P < 0.01]
      and prospective quit attempts (adjusted odds ratio = 1.216, 95% CI 1.114-1.327, P
      < 0.001) when controlling for demographics, smoking characteristics, overall
      salience of anti-smoking information and awareness of anti-smoking material from
      channels other than POS. CONCLUSIONS: Point-of-sale health warnings about tobacco
      are more prominent in Australia than the United Kingdom, the United States or
      Canada and appear to act as a prompt to quitting.

PMID- 21954922
TI  - Pimecrolimus 1% cream for the treatment of rosacea.
AB  - Rosacea is a common inflammatory skin disorder; the pathogenesis is unclear.
      Various treatment options for rosacea are available, but most have limited
      effectiveness. The aim of this study was to investigate the efficacy and safety
      of 1% pimecrolimus cream for the treatment of rosacea. Thirty patients with
      rosacea were enrolled in this 4-week, single-center, open-label study of 1%
      pimecrolimus cream. Patients were instructed to apply the cream to their faces
      twice daily and were not permitted to use any other agents. Clinical efficacy was
      evaluated by a rosacea grading system using photographic documentation and a
      mexameter. The 26 patients who completed the study experienced significantly
      reduced rosacea clinical scores from 9.65 +/- 1.79 at baseline to 7.27 +/- 2.11
      at the end of treatment (P < 0.05). The mexameter-measured erythema index
      decreased significantly from 418.54 +/- 89.56 at baseline to 382.23 +/- 80.04 at
      week 4 (P < 0.05). The side-effects were mostly transient local irritations. The
      results of this study suggest that 1% pimecrolimus cream is an effective and well
      tolerated treatment for patients with mild to moderate inflammatory rosacea.

PMID- 21954928
TI  - Differentiation of closely related isomers: application of data mining techniques
      in conjunction with variable wavelength infrared multiple photon dissociation
      mass spectrometry for identification of glucose-containing disaccharide ions.
AB  - Data mining algorithms have been used to analyze the infrared multiple photon
      dissociation (IRMPD) patterns of gas-phase lithiated disaccharide isomers
      irradiated with either a line-tunable CO(2) laser or a free electron laser (FEL).
      The IR fragmentation patterns over the wavelength range of 9.2-10.6 MUm have been
      shown in earlier work to correlate uniquely with the asymmetry at the anomeric
      carbon in each disaccharide. Application of data mining approaches for data
      analysis allowed unambiguous determination of the anomeric carbon configurations
      for each disaccharide isomer pair using fragmentation data at a single
      wavelength. In addition, the linkage positions were easily assigned. This
      combination of wavelength-selective IRMPD and data mining offers a powerful and
      convenient tool for differentiation of structurally closely related isomers,
      including those of gas-phase carbohydrate complexes.

PMID- 21954923
TI  - Exogenous thrombin delivery promotes collateral capillary arterialization and
      tissue reperfusion in the murine spinotrapezius muscle ischemia model.
AB  - OBJECTIVE: We examined the effects of exogenously delivered thrombin on cell
      recruitment in skeletal muscle and the formation of new collateral arterioles in
      the microvasculature in response to ligation-induced ischemia. METHODS: Thrombin
      or vehicle was locally applied to both ligated and nonoperated Balb/c
      spinotrapezius muscles, which were harvested after three or seven days, imaged
      using confocal microscopy, and analyzed. RESULTS: Thrombin treatment resulted in
      accelerated arterialization of collateral capillaries and accelerated tissue
      reperfusion in ischemic muscles. Uninjured muscle treated with thrombin displayed
      increased vascular cell adhesion molecule 1 expression on arteriole and venule
      endothelium, increased expression of smooth muscle alpha-actin on capillary-sized
      vessels, increased infiltration by CD11b(+) leukocytes, and mast cell
      infiltration and degranulation. CONCLUSIONS: Exogenous delivery of thrombin
      enhances microvascular collateral development in response to ischemic insult, and
      accelerates tissue reperfusion. Elicited responses from multiple cell types
      probably contribute to these effects.

PMID- 21954929
TI  - Evidence for a social function of the anterior temporal lobes: low-frequency rTMS
      reduces implicit gender stereotypes.
AB  - By nature, stereotypes require processes of categorization or semantic
      association, including social information about groups of people. There is
      empirical evidence that the anterior temporal lobe (ATL) processes domain-general
      semantic information, and supports social knowledge. A recent study showed that
      inhibitory repetitive transcranial magnetic stimulation (rTMS) to the ATL reduced
      racial stereotypes on an implicit association test (IAT). However, it was not
      determined whether this was caused by changes to specific social, or general
      semantic processing, or both. The current study addresses these theoretical
      issues. The design investigated the effect of rTMS to the left or right ATL, or a
      sham stimulation, on a social IAT (gender stereotypes), a non-social IAT (living
      versus non-living associations), and a non-semantic control (Stroop) task. The
      results showed that low-frequency rTMS to both left and right ATL significantly
      reduced D-scores on the gender IAT compared to the sham group; however, there
      were no differences on the non-social IAT or the Stroop. The findings show the
      ATL has a role in mediating stereotypes, and the decrease of bias after
      stimulation could be due to weakening of social stereotypical associations either
      within the ATL or via a network of brain regions connected with the ATL.

PMID- 21954931
TI  - Antimalarial activity of physalins B, D, F, and G.
AB  - The antimalarial activities of physalins B, D, F, and G (1-4), isolated from
      Physalis angulata, were investigated. In silico analysis using the similarity
      ensemble approach (SEA) database predicted the antimalarial activity of each of
      these compounds, which were shown using an in vitro assay against Plasmodium
      falciparum. However, treatment of P. berghei-infected mice with 3 increased
      parasitemia levels and mortality, whereas treatment with 2 was protective,
      causing a parasitemia reduction and a delay in mortality in P. berghei-infected
      mice. The exacerbation of in vivo infection by treatment with 3 is probably due
      to its potent immunosuppressive activity, which is not evident for 2.

PMID- 21954933
TI  - Reactivity studies of a disilene with N2O and elemental sulfur.
AB  - In a previous contribution, we have reported on a convenient and high yield
      synthesis of the disilene trans-[(TMS)(2)N(eta(1)-Me(5)C(5))Si?Si(eta(1)
      Me(5)C(5))N(TMS)(2)] (2). Herein, we show the reactions of 2 with N(2)O and S(8).
      The former reaction affords two isomeric (cis- and trans-) dioxadisiletane ring
      compounds. To the best of our knowledge, this is the first report where both cis
      and trans-isomers are isolated from the same disilene precursor and characterized
      structurally by single-crystal X-ray diffraction (XRD) studies. The reaction of 2
      with elemental sulfur yields only the trans-isomer. To investigate this
      dissimilar reaction pattern exhibited by 2, computational studies were performed.
      Density functional theory (DFT) calculations showed that the two dioxadisiletane
      ring isomers are isoenergetic, with the trans isomer being slightly more stable
      than the cis counterpart, by 3.3 kcal/mol, while that is not the case with
      sulfur. All the isolated compounds are characterized by single-crystal XRD
      studies, multinuclear NMR spectroscopy, and electron ionization-mass spectrometry
      (EI-MS).

PMID- 21954932
TI  - Graphene oxide as an enzyme inhibitor: modulation of activity of alpha
      chymotrypsin.
AB  - We have investigated the efficacy of graphene oxide (GO) in modulating enzymatic
      activity. Specifically, we have shown that GO can act as an artificial receptor
      and inhibit the activity of alpha-chymotrypsin (ChT), a serine protease. Most
      significantly, our data demonstrate that GO exhibits the highest inhibition dose
      response (by weight) for ChT inhibition compared with all other reported
      artificial inhibitors. Through fluorescence  spectroscopy and circular dichroism
      studies, we  have shown  that this protein-receptor interaction is highly
      biocompatible and conserves the protein's secondary structure over extended
      periods (>24 h). We have also explored GO-enzyme interactions by controlling the
      ionic strength of the medium, which attenuates the host-guest electrostatic
      interactions. These findings suggest a new generation of enzymatic inhibitors
      that can be applied to other complex proteins by systematic modification of the
      GO functionality.

PMID- 21954934
TI  - Palladium catalyzed stereoselective C-glycosylation of glycals with enol
      triflates.
AB  - An efficient palladium catalyzed C-glycosylation of glycals with enol triflates
      has been established. The coupling reactions took place on the anomeric carbon,
      and the coupling products gave exclusively alpha isomers. The flexibility of the
      reaction was exemplified by the broad spectra of substrate scope, constituted of
      glycals protected with good leaving groups as well as an assortment of enol
      triflates.

PMID- 21954935
TI  - The characteristics of VIM-1-producing Klebsiella pneumoniae from South Africa.
AB  - A study was designed to characterize a carbapenem-resistant Klebsiella pneumoniae
      (KPSA01) isolated from a patient in Gauteng, South Africa without recent travel
      outside South Africa. Molecular characterization was done using isoelectric
      focusing, polymerase chain reaction and sequencing for bla(VIM), bla(IMP),
      bla(NDM), bla(CTX-Ms), bla(OXAs), bla(TEMs), and bla(SHV), plasmid-mediated
      quinolone resistance determinants, multilocus sequencing typing, plasmid replicon
      typing, and addiction factors. KPSA01 produced VIM-1 and belonged to the newly
      described sequence type ST569. The plasmid that harboured bla(VIM) typed within
      the narrow host range IncF replicon group, contained the aadA1 gene cassette, and
      tested positive for the vagCD and ccdAB addiction systems. This is the first
      report of VIM-1-producing K. pneumoniae outside Europe. It is important that
      surveillance studies be undertaken in Africa to determine if VIM-1-producing K.
      pneumoniae are present in significant numbers.

PMID- 21954936
TI  - Catheter ablation of accessory pathway in the treatment of pacemaker-mediated
      tachycardia.
AB  - Pacemaker-mediated tachycardia (PMT) remains a clinical problem in patients with
      dual-chamber pacemaker despite technological advances. The onset mechanism of
      this tachycardia is sensing of retrograde atrial activation after ventricular
      stimulation. Repeated retrograde conduction perpetuates tachycardia.
      Postventricular atrial refractory period prolongation has been used for
      prevention of PMT, but this is not the solution in all cases. We present a case
      with PMT where the retrograde limb is a left accessory pathway, which is treated
      with radiofrequency ablation successfully.

PMID- 21954937
TI  - Effect of oxygen on volatile and sensory characteristics of Cabernet Sauvignon
      during secondary shelf life.
AB  - The oxidation of Cabernet Sauvignon wines during secondary shelf life was studied
      by headspace solid-phase microextraction (HS-SPME) coupled to gas chromatography
      quadrupole mass spectrometry (GC-qMS) and sensory tests, with the support of
      multivariate statistical analyses such as OPLS-DA loading plot and PCA score
      plot. Four different oxidation conditions were established during a 1-week
      secondary shelf life. Samples collected on a regular basis were analyzed to
      determine the changes of volatile chemicals, with sensory characteristics
      evaluated through pattern recognition models. During secondary shelf life the
      separation among collected samples depended on the degree of oxidation in wine.
      Isoamyl acetate, ethyl decanoate, nonanoic acid, n-decanoic acid, undecanoic
      acid, 2-furancarboxylic acid, dodecanoic acid, and phenylacetaldehyde were
      determined to be associated with the oxidation of the wine. PCA sensory
      evaluation revealed that least oxidized wine and fresh wine was well-separated
      from more oxidized wines, demonstrating that sensory characteristics of less
      oxidized wines tend toward "fruity", "citrous", and "sweetness", while those of
      more oxidized wines are positively correlated with "animal", "bitterness", and
      "dairy". The study also demonstrates that OPLS-DA and PCA are very useful
      statistical tools for the understanding of wine oxidation.

PMID- 21954938
TI  - Migratory stopover in the long-distance migrant silver-haired bat, Lasionycteris
      noctivagans.
AB  - 1. Some bat species make long-distance latitudinal migrations between summer and
      winter grounds, but because of their elusive nature, few aspects of their biology
      are well understood. The need for migratory stopover sites to rest and refuel,
      such as used by birds, has been repeatedly suggested, but not previously tested
      empirically in bats. 2. We studied migrating silver-haired bats (Lasionycteris
      noctivagans) at Long Point, ON, Canada. We used digital radio-transmitters to
      track 30 bats using an array of five towers that effectively covered the entire
      region (c. 20 * 40 km). We measured stopover duration and departure direction,
      and documented movement patterns, foraging activity and roost sites. We measured
      body composition on arrival using quantitative magnetic resonance and simulated
      long-distance migration using observed body composition to predict migration
      range and rate. 3. Migration occurred in two waves (late August and mid
      September). Most bats stayed 1-2 days, although two remained >2 weeks. One third
      of the bats foraged while at the site, many foraging opportunistically on nights
      when rain precluded continued migration. Bats roosted in a variety of tree
      species and manmade structures in natural and developed areas. Half of the bats
      departed across Lake Erie (minimum crossing distance c. 38 km) while half
      departed along the shoreline. 4. Simulations predicted a migration rate of c. 250
      275 km per day and suggest that all but one of the bats in our study carried
      sufficient fuel stores to reach the putative wintering area (estimated distance
      1500 km) without further refuelling. 5. Our results suggest that migrating bats
      stopover for sanctuary or short-term rest as opposed to extended rest and
      refuelling as in many songbirds. Daily torpor could reduce energy costs when not
      in flight, minimizing the need for extended stopovers and allowing bats to
      potentially complete their migration at a fraction of the time and energy cost of
      similar sized birds.

PMID- 21954939
TI  - DFT studies of the interactions of a graphene layer with small water aggregates.
AB  - We have investigated the structure, adsorption, electronic states, and charge
      transfer of small water aggregates on the surface of a graphene layer using
      density functional theory. Our calculations were focused on water adsorbates
      containing up to five water molecules interacting with one and both sides of a
      perfect freestanding sheet. Different orientations of the aggregates with respect
      to the graphene sites were considered. The results show that the adsorption
      energy of one water molecule is primarily determined by its orientation, although
      it is also strongly dependent on the implemented functional scheme. Despite its
      intrinsic difficulties with dispersion interactions, the Perdew and Wang's
      exchange-correlation functional may be a viable alternative to investigate the
      adsorption of large molecular aggregates on a graphene surface. Although water
      physisorption is expected to occur in the regime of droplets, we found no induced
      impurity states close to the Fermi level of graphene interacting with small water
      clusters. In order to investigate the donor/acceptor tendency of the water
      clusters on graphene, we have performed a Bader charge analysis. Considering the
      charge transfer mechanism, we have noticed that it should preferentially occur
      from water to graphene only when the oxygen atom is pointing toward the surface.
      Otherwise, and in the case of larger adsorbed clusters, charge transfers
      systematically occur from graphene to water.

PMID- 21954940
TI  - Is self interdental cleaning associated with dental plaque levels, dental
      calculus, gingivitis and periodontal disease?
AB  - BACKGROUND AND OBJECTIVE: To ascertain whether interdental cleaning behaviours of
      Australian adults were associated with lower levels of plaque, gingivitis and
      periodontal disease. MATERIAL AND METHODS: Data were obtained from the National
      Survey of Adult Oral Health 2004-06. Outcome variables were three indicators of
      oral hygiene outcomes (the presence or not of dental plaque, dental calculus and
      gingivitis) and two of periodontal disease (the presence or not of at least one
      tooth with a periodontal pocket or clinical attachment loss of >= 4 mm). The
      independent variable was classified into the following three groups: regularly
      clean interproximally 'at least daily' (daily+); 'less than daily' (< daily); and
      'do not regularly clean interproximally' (reference group). Poisson regression
      with robust variance estimation was used to calculate prevalence ratios (PRs) and
      95% confidence intervals (95% CIs) relative to the reference group, adjusted for
      covariates. RESULTS: Regular self interdental cleaning was associated with less
      dental plaque (< daily, PR = 0.89, 95% CI = 0.84, 0.95; and daily+, PR = 0.89,
      95% CI = 0.82, 0.96), less dental calculus (< daily, PR = 0.88, 95% CI = 0.80,
      0.97; and daily+, PR = 0.79, 95% CI = 0.70, 0.89) and lower levels of
      moderate/severe gingivitis (daily+, PR = 0.85, 95% CI = 0.77, 0.94). Periodontal
      pocketing was less likely for the < daily group (PR = 0.61, 95% CI = 0.46, 0.82),
      but was not associated with daily+ cleaning (PR = 0.99, 95% CI = 0.663, 1.49).
      There was not a significant association between interdental cleaning and clinical
      attachment loss (< daily, PR = 0.90, 95% CI = 0.77, 1.05; and daily+, PR = 1.17,
      95% CI = 0.95, 1.44). CONCLUSION: Regular interdental cleaning was associated
      with better oral hygiene outcomes, such as dental plaque and gingivitis, although
      there was no significant association between regular interdental cleaning and
      clinical attachment loss.

PMID- 21954941
TI  - Early evolutionary differentiation of morphological variation in the mandible of
      South American caviomorph rodents (Rodentia, Caviomorpha).
AB  - Caviomorphs are a clade of South American rodents recorded at least since the
      early Oligocene (> 31.5 Ma) that exhibit ample eco-morphological variation. It
      has been proposed that phylogenetic structure is more important than ecological
      factors for understanding mandibular shape variation in this clade. This was
      interpreted as a result of the long-standing evolutionary history of caviomorphs
      and the early divergence of major lineages. In this work, we test this hypothesis
      through the analysis of morphological variation in the mandible of living and
      extinct species and compare this information with that obtained through
      comparative phylogenetic analyses. Our results support the hypothesis of early
      origin of mandibular variation; moreover, they suggest the conservation of early
      differentiated morphologies, which could indicate the existence of constrained
      evolutionary diversification.

PMID- 21954942
TI  - Structure and properties of the Ca(2+)-binding CUB domain, a widespread ligand
      recognition unit involved in major biological functions.
AB  - CUB domains are 110-residue protein motifs exhibiting a beta-sandwich fold and
      mediating protein-protein interactions in various extracellular proteins. Recent
      X-ray structural and mutagenesis studies have led to the identification of a
      particular CUB domain subset, cbCUB (Ca(2+)-binding CUB domain). Unlike other CUB
      domains, these harbour a homologous Ca(2+)-binding site that underlies a
      conserved binding site mediating ionic interaction between two of the three
      conserved acidic Ca(2+) ligands and a basic (lysine or arginine) residue of a
      protein ligand, similar to the interactions mediated by the low-density
      lipoprotein receptor family. cbCUB-mediated protein-ligand interactions usually
      involve multipoint attachment through several cbCUBs, resulting in high-affinity
      binding through avidity, despite the low affinity of individual interactions. The
      aim of the present review is to summarize our current knowledge about the
      structure and functions of cbCUBs, which represent the majority of the known CUB
      repertoire and are involved in a variety of major biological functions, including
      immunity and development, as well as in various cancer types. Examples discussed
      in the present review include a wide range of soluble and membrane-associated
      human proteins, as well as some archaeal and invertebrate proteins. The fact that
      these otherwise unrelated proteins share a common Ca(2+)-dependent ligand-binding
      ability suggests a mechanism inherited from very primitive ancestors. The
      information provided in the present review should stimulate further
      investigations on the crucial interactions mediated by cbCUB-containing proteins.

PMID- 21954943
TI  - PDZ domains: the building blocks regulating tumorigenesis.
AB  - Over 250 PDZ (PSD95/Dlg/ZO-1) domain-containing proteins have been described in
      the human proteome. As many of these possess multiple PDZ domains, the potential
      combinations of associations with proteins that possess PBMs (PDZ-binding motifs)
      are vast. However, PDZ domain recognition is a highly specific process, and much
      less promiscuous than originally thought. Furthermore, a large number of PDZ
      domain-containing proteins have been linked directly to the control of processes
      whose loss, or inappropriate activation, contribute to the development of human
      malignancies. These regulate processes as diverse as cytoskeletal organization,
      cell polarity, cell proliferation and many signal transduction pathways. In the
      present review, we discuss how PBM-PDZ recognition and imbalances therein can
      perturb cellular homoeostasis and ultimately contribute to malignant progression.

PMID- 21954944
TI  - Targeting tumour cells at the entrance.
AB  - Metabolism in tumour cells is adapted to the demands of a growing cell. The
      Warburg effect and increased use of glutamine are two well-known adaptations of
      tumour metabolism. Both require transporters to allow uptake of substrates and
      efflux of products. Differentiated cells are less reliant on these pathways and
      as a result are less vulnerable to drugs that curtail nutrient uptake. Thus drugs
      that reduce nutrient uptake are promising candidates for tumour therapy. Detailed
      understanding of tumour cell biology will allow the generation of new
      chemotherapeutic drugs with limited side effects.

PMID- 21954946
TI  - The effect of fluid viscosity on the hemodynamic energy changes during operation
      of the pulsatile ventricular assist device.
AB  - Blood viscosity during operation of ventricular assist device (VAD) can be
      changed by various conditions such as anemia. It is known generally that the
      blood viscosity can affect vascular resistance and lead to change of blood flow.
      In this study, the effect of fluid viscosity variation on hemodynamic energy was
      evaluated with a pulsatile blood pump in a mock system. Six solutions were used
      for experiments, which were composed of water and glycerin and had different
      viscosities of 2, 2.5, 3, 3.5, 4, and 4.5 cP. The hemodynamic energy at the
      outlet cannula was measured. Experimental results showed that mean pressure was
      increased in accordance with the viscosity increase. When the viscosity
      increased, the mean pressure was also increased. However, the flow was decreased
      according to the viscosity increase. Energy equivalent pressure value was
      increased according to the viscosity-induced pressure rise; however, surplus
      hemodynamic energy value did not show any apparent changing trend. The
      hemodynamic energy made by the pulsatile VAD was affected by the viscosity of the
      circulating fluid.

PMID- 21954947
TI  - Evidence of increasing age of onset of cannabis use among younger Australians.
AB  - AIM: To determine whether declines in the prevalence of cannabis use in Australia
      have been accompanied by changes in age of onset of cannabis use. DESIGN: A
      retrospective cohort study. To account for right censoring error we contrasted
      the mean age of onset for comparable age groups across the four surveys conducted
      from 1998 to 2007. Kaplan-Meier failure graphs were used to describe how the
      cumulative risk of first use of cannabis varied across birth cohorts born from
      1947 to 1993. SETTING: Australian data collected in the nationally
      representative, triennial, National Drug Strategy Household Surveys (NDSHS)
      PARTICIPANTS: A total of 88,268 Australian household residents aged 14 years and
      older. MEASUREMENTS: Life-time use of cannabis and age of first use. FINDINGS:
      For respondents under the age of 20 years, mean age of first use of cannabis has
      increased from 14.6 years in 1998 to 15.2 years in 2007. CONCLUSIONS: The decline
      in cannabis use prevalence that has occurred since 1998 in Australia has been
      accompanied by an increase in age of first use among those aged under 20 years.

PMID- 21954948
TI  - The validity of the Addenbrooke's Cognitive Examination-Revised (ACE-R) in acute
      stroke.
AB  - PURPOSE: The purpose was to examine the validity of the Addenbrooke's Cognitive
      Examination Revised (ACE-R) as a screening measure to detect cognitive impairment
      after stroke. METHODS: Stroke patients in hospital were recruited and the ACE-R,
      which includes the Mini-Mental Status Examination (MMSE), was administered,
      followed by a battery of neuropsychological tests, which served as the 'gold
      standard' for classification of cognitive impairment. The diagnostic validity of
      the ACE-R was determined by ROC analysis. RESULTS: Of the 101 patients who
      completed the ACE-R, 61 also completed the neuropsychological assessment. Both
      the MMSE and the ACE-R were found to have inadequate diagnostic validity for the
      detection of overall cognitive impairment (MMSE AUC = 0.53, p > 0.05; ACE-R AUC =
      0.53, p > 0.05). The ACE-R subscales predicted impairment in specific cognitive
      domains significantly better than chance; Visuospatial (AUC = 0.71, p < 0.05),
      Fluency (AUC = 0.72, p< 0.05) and Attention and Orientation (AUC = 0.80, p <
      0.05). However, no cut-off score for any subscale gave both adequate levels of
      sensitivity and specificity for the detection of impairment in specific areas of
      cognitive functioning. CONCLUSIONS: The ACE-R was not a suitable measure to
      screen for overall cognitive impairment in acute stroke patients, but was able to
      detect impairment in visuospatial, attention and executive domains.

PMID- 21954945
TI  - Biological interactions of graphene-family nanomaterials: an interdisciplinary
      review.
AB  - Graphene is a single-atom thick, two-dimensional sheet of hexagonally arranged
      carbon atoms isolated from its three-dimensional parent material, graphite.
      Related materials include few-layer-graphene (FLG), ultrathin graphite, graphene
      oxide (GO), reduced graphene oxide (rGO), and graphene nanosheets (GNS). This
      review proposes a systematic nomenclature for this set of Graphene-Family
      Nanomaterials (GFNs) and discusses specific materials properties relevant for
      biomolecular and cellular interactions. We discuss several unique modes of
      interaction between GFNs and nucleic acids, lipid bilayers, and conjugated small
      molecule drugs and dyes. Some GFNs are produced as dry powders using thermal
      exfoliation, and in these cases, inhalation is a likely route of human exposure.
      Some GFNs have aerodynamic sizes that can lead to inhalation and substantial
      deposition in the human respiratory tract, which may impair lung defense and
      clearance leading to the formation of granulomas and lung fibrosis. The limited
      literature on in vitro toxicity suggests that GFNs can be either benign or toxic
      to cells, and it is hypothesized that the biological response will vary across
      the material family depending on layer number, lateral size, stiffness,
      hydrophobicity, surface functionalization, and dose. Generation of reactive
      oxygen species (ROS) in target cells is a potential mechanism for toxicity,
      although the extremely high hydrophobic surface area of some GFNs may also lead
      to significant interactions with membrane lipids leading to direct physical
      toxicity or adsorption of biological molecules leading to indirect toxicity.
      Limited in vivo studies demonstrate systemic biodistribution and biopersistence
      of GFNs following intravenous delivery. Similar to other smooth, continuous,
      biopersistent implants or foreign bodies, GFNs have the potential to induce
      foreign body tumors. Long-term adverse health impacts must be considered in the
      design of GFNs for drug delivery, tissue engineering, and fluorescence-based
      biomolecular sensing. Future research is needed to explore fundamental biological
      responses to GFNs including systematic assessment of the physical and chemical
      material properties related to toxicity. Complete materials characterization and
      mechanistic toxicity studies are essential for safer design and manufacturing of
      GFNs in order to optimize biological applications with minimal risks for
      environmental health and safety.

PMID- 21954949
TI  - Transcultural differences in brain activation patterns during theory of mind
      (ToM) task performance in Japanese and Caucasian participants.
AB  - BACKGROUND: Theory of mind (ToM) functioning develops during certain phases of
      childhood. Factors such as language development and educational style seem to
      influence its development. Some studies that have focused on transcultural
      aspects of ToM development have found differences between Asian and Western
      cultures. To date, however, little is known about transcultural differences in
      neural activation patterns as they relate to ToM functioning. EXPERIMENTAL
      METHODS: The aim of our study was to observe ToM functioning and differences in
      brain activation patterns, as assessed by functional magnetic resonance imaging
      (fMRI). This study included a sample of 18 healthy Japanese and 15 healthy
      Caucasian subjects living in Japan. We presented a ToM task depicting geometrical
      shapes moving in social patterns. We also administered questionnaires to examine
      empathy abilities and cultural background factors. RESULTS: Behavioral data
      showed no significant group differences in the subjects' post-scan descriptions
      of the movies. The imaging results displayed stronger activation in the medial
      prefrontal cortex (MPFC) in the Caucasian sample during the presentation of ToM
      videos. Furthermore, the task-associated activation of the MPFC was positively
      correlated with autistic and alexithymic features in the Japanese sample.
      DISCUSSION: In summary, our results showed evidence of culturally dependent
      sociobehavioral trait patterns, which suggests that they have an impact on brain
      activation patterns during information processing involving ToM.

PMID- 21954950
TI  - Spontaneous dislocation of intraocular lens as a late complication of
      uncomplicated cataract surgery: a case series.
AB  - Five patients having uncomplicated phacoemulsification were implanted with CT
      Asphina 603P intraocular lenses into the capsular bag. After a few months, three
      of the patients had haptic flexion anterior to the optic despite minimal capsular
      fibrosis. One patient had spontaneous dislocation of the intraocular lens into
      the anterior chamber with only minimal capsular fibrosis. Another patient had one
      haptic dislocated out of the bag. Late intraocular lens dislocation is also seen
      in newly designed preloaded intraocular lenses despite the absence of significant
      capsular fibrosis. Haptic-optic junction design and intraocular lens material
      play important roles in such complication. A slightly large capsulorhexis might
      be a deterrent for implantation of this intraocular lens.

PMID- 21954951
TI  - Removable intraductal stenting in duct-to-duct biliary reconstruction in liver
      transplantation.
AB  - Biliary reconstruction during liver transplantation (LT) is most oftenly
      performed by duct-to-duct biliary anastomosis. We hypothesized that the internal
      stenting might diminish the incidence and severity of biliary complications in
      patients receiving small duct size donor grafts. The purpose of this study was to
      report a technique of biliary reconstruction, including intraductal stent tube
      (IST) placement followed by postoperative endoscopic removal. A custom-made
      segment of a T-tube was placed into the bile in 20 patients in whom the diameter
      of the graft bile duct was smaller than 5 mm. The tube was removed endoscopically
      4-8 months after LT, or in case of IST-related adverse events. After a median
      follow-up of 15.2 (range 2.5-27.5) months, endoscopic removal of the IST was
      performed in 17 patients. No technical failure and no procedure-related
      complications were recorded during drain removal. Biliary complications occurred
      in four patients, including one cholangitis, one hemobilia, one asymptomatic
      biliary leakage, and one anastomotic stricture. No biliary complication occurred
      in the group of patients who underwent deceased donor whole graft LT. IST is
      technically feasible and safe, and may help to prevent severe biliary
      complication when duct-to-duct biliary anastomosis is performed on small size
      bile ducts.

PMID- 21954952
TI  - Identification problems with sterile fungi, illustrated by a keratitis due to a
      non-sporulating Chaetomium-like species.
AB  - A 39-year-old farm worker was injured in her right eye by a piece of wire, which
      resulted in a corneal ulcer unresponsive to antibiotic treatment. The clinical
      appearance was that of a corneal infiltrate with feathery borders resembling
      fungal keratitis. Corneal scrapings were collected and the patient was started on
      natamycin 5% eye drops, fluconazole 0.3% eye drops, and oral fluconazole. A non
      sporulating fungus was isolated from the samples. Based upon macroscopic and
      microscopic morphologic features, it was provisionally identified as a
      Papulaspora species due to the fact that members of this genus generally do not
      form diagnostically useful conidia. However, it was found through the use of ITS
      sequencing that the isolate clustered within the ascomycete genus Chaetomium. The
      sequence did not fully match with any sequences of available ex-type strains of
      Chaetomium, Thielavia and Papulaspora and hence might belong to an undescribed
      specie. However, without diagnostic morphological features the taxon cannot be
      introduced as a novel member of the genus Chaetomium. Antifungal susceptibility
      testing was performed according to published standards. The corneal ulcer was
      successfully treated with six weeks of antifungal therapy.

PMID- 21954953
TI  - In vitro activity of Amphotericin B against zygomycetes isolated from deep
      mycoses: a comparative study between incubation in aerobic and hyperbaric
      atmosphere.
AB  - Many case reports suggest that the use of hyperbaric oxygen therapy associated
      with surgical and medical approaches may contribute to restricting the growth of
      zygomycetes in patient tissue. The primary aim of this study was to obtain data
      concerning the in vitro susceptibility of 22 zygomycetes to antifungals such as
      amphotericin B and posaconazole, and to compare the in vitro development of these
      fungi in aerobic normobaric versus hyperoxic normobaric and hyperbaric
      atmosphere. None of the zygomycetes grew after 24-hour and 72-hour incubation in
      a hyperoxic hyperbaric (2 or 3 ATA) atmosphere. However, when plates were
      maintained at room temperature in aerobic conditions, colonies were observed from
      36-96 h after inoculation, while minimum inhibitory concentration (MIC) values
      remained the same. This preliminary in vitro study focuses on the in vitro
      examination of combination therapies to potentiate antifungal activity. Both
      hyperoxic hyperbaric conditions and a single antifungal agent, as well as
      combinations of different antifungal drugs were used. Results suggest an
      impressive in vitro fungistatic activity of the hyperoxic hyperbaric atmosphere,
      even if the antifungal effect is strictly time-dependent using these incubation
      conditions.

PMID- 21954954
TI  - Identification of rare macroconidia-producing dermatophytic fungi by real-time
      PCR.
AB  - To understand the pathogenicity and clinical significance of dermatophytes (also
      known as ringworms), the correct identification of these molds is essential.
      However, in routine practice they are notoriously difficult to classify and
      identify. The morphology of macroconidia, which are abundantly produced under
      suitable in vitro conditions, have provided useful criteria for the
      identification of many of the dermatophytes. However, several of them, including
      Microsporum audouinii, M. ferrugineum, Trichophyton concentricum, T.
      schoenleinii, T. verrucosum, and T. violaceum (including T. soudanense and T.
      yaoundei) rarely produce macroconidia and cannot be easily identified. The
      objective of this study was to design, optimize, and evaluate real-time PCR as a
      tool for identifying dermatophytic fungi in a laboratory setting. The performance
      of the assay was evaluated using 64 dermatophyte isolates, i.e., 35 rare
      macroconidia-producing reference strains, including the six species mentioned
      above, and 29 clinical isolates from our laboratory, including M. canis (4), T.
      mentagrophytes (2), T. rubrum (20), T. rubrum with the 'raubitschekii' morphotype
      (2), and T. tonsurans (1). Real-time PCR correctly identified 10 taxonomically
      distinct dermatophytes, particularly rare macroconidia-producing species, with
      excellent sensitivity (100%). The advantages of the assay include the provision
      of accurate and reliable diagnoses of dermatophytic fungi.

PMID- 21954955
TI  - Pravastatin inhibits farnesol production in Candida albicans and improves
      survival in a mouse model of systemic candidiasis.
AB  - Candidemia remains a major cause of morbidity and mortality, especially in
      immunocompromised patients. A strategy of reducing virulence and virulence
      factors of Candida spp. is an attractive approach for the treatment of serious
      infections caused by these yeasts. Recently, farnesol has been reported to be a
      quorum-sensing autoinducer, as well as a virulence factor of C. albicans. In the
      present study, we examined the effects of pravastatin, a 3-hydroxy-3
      methylglutaryl-CoA (HMG-CoA) reductase inhibitor on the in vitro production of
      farnesol. In addition, the synergistic effects of pravastatin with fluconazole
      (FLC) were examined in a mouse model of systemic infections. In vitro experiments
      demonstrated that pravastatin had synergistic activity with FLC as judged by
      fractional inhibitory concentration index (FICI) and suppression of farnesol
      production at sub-minimum inhibitory concentrations. Furthermore, significant
      improvement of survival in systemic infection models was shown with pravastatin
      supplementation. The survival benefits of pravastatin were correlated with
      reductions of fungal burden. These data suggest the potential of pravastatin as a
      supportive therapy against C. albicans infections. Synergistic antifungal
      activity and suppression of HMG-CoA reductase-associated Candida virulence
      factors, including farnesol, may explain, at least in part, the in vivo efficacy
      of pravastatin.

PMID- 21954956
TI  - Study on the T-helper cell 1/2 cytokine profile in blister fluid of patients with
      herpes zoster and its clinical significance.
AB  - Herpes zoster (HZ) is a Varicella zoster virus infection disease. Previous
      studies have presumed the connection between development of HZ and involvement of
      cellular immunity in peripheral blood. However, whether cellular immunity plays a
      role in the local skin lesion has not been addressed. To explore the levels of T
      helper cell (Th)1/Th2 type cytokine profiles in the blister fluid of the skin
      lesions from the patients with HZ and its role in pathogenesis, we used the
      cytometric bead array kit to compare the levels of cytokines (interleukin [IL]-2,
      tumor necrosis factor [TNF]-alpha, IL-10 and IL-4) in blister fluid from 46
      patients with those from the suction blister fluids from 20 volunteers without
      any infectious disease (the control group). The results indicated that the levels
      of Th1 cytokines, IL-2 and TNF-alpha in the blister fluid from the patients' skin
      lesions were significantly lower than those from the control group, whereas the
      levels of Th2 cytokines IL-10 and IL-4 were significantly higher than those in
      the control group. Moreover, significant variation of the levels of Th1/Th2
      cytokines (IL-2, TNF-alpha, IL-10 and IL-4) in the blister fluid from the HZ
      patients' lesions was also observed among different stages of the disease. It is
      concluded that a cytokine imbalance was present in the local lesions of patients
      with HZ during disease development. Our data suggested that the Th immunity was
      associated with disease activity, which may play an important role in the
      pathogenesis of HZ.

PMID- 21954958
TI  - Modular approach to saturated and alpha,beta-unsaturated ketones.
AB  - 2-Fluoro-6-pyridinyloxy derivatives of 2-ethoxyvinyl carbinols react with
      radicals derived from xanthates by an addition-fragmentation pathway to give
      highly functionalized ketones after acid hydrolysis. 1,4-Diketones are readily
      accessible by this approach. alpha,beta-Unsaturated ketones can be obtained by
      starting with geminal acetoxy xanthates prepared by addition of a simpler
      xanthate to vinyl acetate.

PMID- 21954959
TI  - Triterpenoid constituents from the roots of Paeonia rockii ssp. rockii.
AB  - An investigation of a chloroform-soluble extract from the roots of Paeonia rockii
      ssp. rockii yielded three new noroleanane triterpenoids (1-3) together with 19
      known compounds. Their structures were established by analysis of the
      spectroscopic data. The effects of this chloroform-soluble extract and its major
      constituents on cell proliferation and apoptosis of a panel of human cancer cell
      lines (melanoma M-14, colon cancer HT-29, breast cancer MCF-7) were evaluated by
      the MTT bioassay and propidium iodide staining, respectively, in comparison with
      normal human embryonic kidney cells (HEK-293). Two of the triterpenoids,
      betulinic acid (4) and oleanolic acid (5), and the crude extract were cytotoxic
      and induced apoptosis selectively in the M-14 melanoma cell line. This effect was
      reversed by the caspase-inhibitor z-VAD-fmk, suggesting that such action is
      mediated by caspase-3 activation.

PMID- 21954957
TI  - Noncovalent DNA binding drives DNA alkylation by leinamycin: evidence that the
      Z,E-5-(thiazol-4-yl)-penta-2,4-dienone moiety of the natural product serves as an
      atypical DNA intercalator.
AB  - Molecular recognition and chemical modification of DNA are important in medicinal
      chemistry, toxicology, and biotechnology. Historically, natural products have
      revealed many interesting and unexpected mechanisms for noncovalent DNA binding
      and covalent DNA modification. The studies reported here characterize the
      molecular mechanisms underlying the efficient alkylation of duplex DNA by the
      Streptomyces-derived natural product leinamycin. Previous studies suggested that
      alkylation of duplex DNA by activated leinamycin (2) is driven by noncovalent
      association of the natural product with the double helix. This is striking
      because leinamycin does not contain a classical noncovalent DNA-binding motif,
      such as an intercalating unit, a groove binder, or a polycation. The experiments
      described here provide evidence that leinamycin is an atypical DNA-intercalating
      agent. A competition binding assay involving daunomycin-mediated inhibition of
      DNA alkylation by leinamycin provided evidence that activated leinamycin binds to
      duplex DNA with an apparent binding constant of approximately 4.3 +/- 0.4 * 10(3)
      M(-1). Activated leinamycin caused duplex unwinding and hydrodynamic changes in
      DNA-containing solutions that are indicative of DNA intercalation.
      Characterization of the reaction of activated leinamycin with palindromic
      duplexes containing 5'-CG and 5'-GC target sites, bulge-containing duplexes, and
      5-methylcytosine-containing duplexes provided evidence regarding the orientation
      of leinamycin with respect to target guanine residues. The data allow
      construction of a model for the leinamycin-DNA complex suggesting how a modest
      DNA-binding constant combines with proper positioning of the natural product to
      drive efficient alkylation of guanine residues in the major groove of duplex DNA.

PMID- 21954960
TI  - Redox balance in the aging microcirculation: new friends, new foes, and new
      clinical directions.
AB  - Cardiovascular aging is associated with a decline in the function of the vascular
      endothelium. Considerable evidence indicates that age-induced impairment of
      endothelium-dependent vasodilation results from a reduction in the availability
      of nitric oxide (NO(*) ). NO(*) can be scavenged by reactive oxygen species
      (ROS), in particular by superoxide radical (O(2) (*-) ), and age-related
      increases in ROS have been demonstrated to contribute to reduced endothelium
      dependent vasodilation in numerous large artery preparations. In contrast,
      emerging data suggest that ROS may play a compensatory role in endothelial
      function of the aging microvasculature. The primary goal of this review is to
      discuss reports in the literature which indicate that ROS function as important
      signaling molecules in the aging microvasculature. Emphasis is placed upon
      discussion of the emerging roles of hydrogen peroxide (H(2) O(2) ) and
      peroxynitrite (ONOO(*-) ) in the aging microcirculation. Overall, existing data
      in animal models suggest that maintenance in the balance of ROS is critical to
      successful microvascular aging. The limited work that has been performed to
      investigate the role of ROS in human microvascular aging is also discussed, and
      the need for future investigations of ROS signaling in older humans is
      considered.

PMID- 21954961
TI  - Raa4 is a trans-splicing factor that specifically binds chloroplast tscA intron
      RNA.
AB  - During trans-splicing of discontinuous organellar introns, independently
      transcribed coding sequences are joined together to generate a continuous mRNA.
      The chloroplast psaA gene from Chlamydomonas reinhardtii encoding the P(700) core
      protein of photosystem I (PSI) is split into three exons and two group IIB
      introns, which are both spliced in trans. Using forward genetics, we isolated a
      novel PSI mutant, raa4, with a defect in trans-splicing of the first intron.
      Complementation analysis identified the affected gene encoding the 112.4 kDa Raa4
      protein, which shares no strong sequence identity with other known proteins. The
      chloroplast localization of the protein was confirmed by confocal fluorescence
      microscopy, using a GFP-tagged Raa4 fusion protein. RNA-binding studies showed
      that Raa4 binds specifically to domains D2 and D3, but not to other conserved
      domains of the tripartite group II intron. Raa4 may play a role in stabilizing
      folding intermediates or functionally active structures of the split intron RNA.

PMID- 21954962
TI  - Effect on ring current of the Kekule vibration in aromatic and antiaromatic
      rings.
AB  - Derivative current-density maps are used to follow the changes in ring-current
      (and hence, on the magnetic criterion, the changes in aromaticity) with the
      Kekule vibrations of the prototypical aromatic, antiaromatic, and nonaromatic
      systems of benzene, cyclooctatetraene (COT), and borazine. Maps are computed at
      the ipsocentric CHF/6-31G**//RHF/6-31G** level. The first-derivative map for
      benzene shows a growing-in of localized bond currents, and the second-derivative
      map shows a pure, paratropic "antiring-current", leading to the conclusion that
      vibrational motion along the Kekule mode will reduce the net aromaticity of
      benzene, on average. For planar-constrained D(4h) COT, the Kekule mode (positive
      for reduction of bond-length alternation) increases paratropicity at both first
      and second order, indicating an average increase in antiaromaticity with zero
      point motion along this mode. On the ring-current criterion, breathing expansions
      of benzene and D(4h) COT reduce aromaticity and increase antiaromaticity,
      respectively.

PMID- 21954963
TI  - Three-dimensional porous metal-metalloporphyrin framework consisting of
      nanoscopic polyhedral cages.
AB  - An unprecedented nanoscopic polyhedral cage-containing metal-metalloporphyrin
      framework, MMPF-1, has been constructed from a custom-designed porphyrin ligand,
      5,15-bis(3,5-dicarboxyphenyl)porphine, that links Cu(2)(carboxylate)(4) moieties.
      A high density of 16 open copper sites confined within a nanoscopic polyhedral
      cage has been achieved, and the packing of the porphyrin cages via an "ABAB"
      pattern affords MMPF-1 ultramicropores which render it selective toward
      adsorption of H(2) and O(2) over N(2), and CO(2) over CH(4).

PMID- 21954965
TI  - Significance of combination therapy of zoledronic acid and gemcitabine on
      pancreatic cancer.
AB  - In the present study, we examined the cytotoxic effects of combination therapy
      with zoledronic acid (ZOL) and gemcitabine (GEM) on pancreatic cancer cells in
      vitro and in vivo. Four human pancreatic cancer cell lines were treated with ZOL,
      GEM or a combination of both, and the effects of the respective drug regimens on
      cell proliferation, invasion and matrix metalloproteinase (MMP) expression were
      examined. A pancreatic cancer cell line was also intrasplenically or
      orthotopically implanted into athymic mice and the effects of these drugs on
      tumor metastasis and growth in vivo were evaluated by histological and
      immunohistochemical analyses. Combination treatment with low doses of ZOL and GEM
      efficiently inhibited the proliferation (P < 0.001) and invasion (P < 0.001) of
      pancreatic cancer cells in vitro. Western blotting assay revealed that MMP-2 and
      MMP-9 expression levels were decreased after ZOL treatment. In vivo, combined
      treatment significantly inhibited tumor growth (P < 0.05) and the development of
      liver metastasis (P < 0.05). These data revealed that ZOL and GEM, when used in
      combination, have significant antitumor, anti-metastatic and anti-angiogenic
      effects on pancreatic cancer cells. The present study is the first to report the
      significance of the combination treatment of ZOL and GEM in pancreatic cancer
      using an in vivo model. These data are promising for the future application of
      this drug regimen in patients with pancreatic cancer.

PMID- 21954964
TI  - Research review: gene-environment interaction research in youth depression - a
      systematic review with recommendations for future research.
AB  - BACKGROUND: Depression is a major public health problem among youth, currently
      estimated to affect as many as 9% of US children and adolescents. The recognition
      that both genes (nature) and environments (nurture) are important for
      understanding the etiology of depression has led to a rapid growth in research
      exploring gene-environment interactions (GxE). However, there has been no
      systematic review of GxE in youth depression to date. METHODS: The goal of this
      article was to systematically review evidence on the contribution of GxE to the
      risk of child and adolescent depression. Through a search of PubMed and PsycINFO
      databases to 1 April 2010, we identified 20 candidate gene-environment
      interaction studies focused on depression in youth (up to age 26) and compared
      each study in terms of the following characteristics: research design and sample
      studied; measure of depression and environment used; genes explored; and GxE
      findings in relation to these factors. RESULTS: In total, 80% of studies (n = 16)
      found at least one significant GxE association. However, there was wide variation
      in methods and analyses adopted across studies, especially with respect to
      environmental measures used and tests conducted to estimate GxE. This
      heterogeneity made it difficult to compare findings and evaluate the strength of
      the evidence for GxE. CONCLUSIONS: The existing body of GxE research on
      depression in youth contains studies that are conceptually and methodologically
      quite different, which contributes to mixed findings and makes it difficult to
      assess the current state of the evidence. To decrease this heterogeneity, we
      offer 20 recommendations that are focused on: (a) reporting GxE research; (b)
      testing and reporting GxE effects; (c) conceptualizing, measuring and analyzing
      depression; (d) conceptualizing, measuring and analyzing environment; (e)
      increasing power to test for GxE; and (f) improving the quality of genetic data
      used. Although targeted to GxE research on depression, these recommendations can
      be adopted by GxE researchers focusing on other mental health outcomes.

PMID- 21954966
TI  - Comparison of second-generation antipsychotic treatment on psychiatric
      hospitalization in Medicaid beneficiaries with bipolar disorder.
AB  - OBJECTIVE: To compare second-generation antipsychotics on time to and cost of
      psychiatric hospitalization in Medicaid beneficiaries with bipolar disorder.
      METHODS: Retrospective study using healthcare claims from 10 US state Medicaid
      programs. Included beneficiaries were aged 18-64, initiated a single second
      generation antipsychotic (aripiprazole, olanzapine, quetiapine, risperidone, or
      ziprasidone) between 1/1/2003-6/30/2008 (initiation date=index), and had a
      medical claim with an ICD-9-CM diagnosis code for bipolar disorder. A 360-day
      post-index period was used to measure time to and costs of psychiatric
      hospitalization (inpatient claims with a diagnosis code for a mental disorder
      [ICD-9-CM 290.xx-319.xx] in any position). Cox proportional hazards models and
      Generalized Linear Models compared time to and costs of psychiatric
      hospitalization, respectively, in beneficiaries initiating aripiprazole vs each
      other second-generation antipsychotic, adjusting for beneficiaries' baseline
      characteristics. RESULTS: Included beneficiary characteristics: mean age 36
      years, 77% female, 80% Caucasian, aripiprazole (n=2553), mean time to psychiatric
      hospitalization or censoring=85 days; olanzapine (n=4702), 81 days; quetiapine
      (n=9327), 97 days; risperidone (n=4377), 85 days; ziprasidone (n=1520), 82 days.
      After adjusting for baseline characteristics, time to psychiatric hospitalization
      in beneficiaries initiating aripiprazole was longer compared to olanzapine
      (hazard ratio [HR]=1.52, p<0.001), quetiapine (HR=1.40, p<0.001), ziprasidone
      (HR=1.33, p=0.032), and risperidone, although the latter difference did not reach
      significance (HR=1.18, p=0.13). The adjusted costs of psychiatric hospitalization
      in beneficiaries initiating aripiprazole were significantly lower compared to
      those initiating quetiapine (incremental per-patient per-month difference=$42,
      95% CI=$16-66, p<0.05), but not significantly lower for the other comparisons.
      LIMITATIONS: This study was based on a non-probability convenience sample of the
      Medicaid population. Analyses of administrative claims data are subject to coding
      and classification error. CONCLUSIONS: Medicaid beneficiaries with bipolar
      disorder initiating aripiprazole had significantly longer time to psychiatric
      hospitalization than those initiating olanzapine, quetiapine, or ziprasidone, and
      significantly lower adjusted costs for psychiatric hospitalization than those
      initiating quetiapine.

PMID- 21954967
TI  - Ventricular activation sequence during left ventricular pacing promotes QRS
      complex oversensing in the atrial channel.
AB  - BACKGROUND: Left ventricular (LV)-only pacing has a significant effect on delay
      in depolarization of parts of the ventricles that are likely oversensed in the
      right atrial channel. The study aimed to assess the impact of ventricular
      activation sequence on QRS oversensing and far-field endless-loop pacemaker
      tachycardia (ELT) in patients who received cardiac resynchronization therapy
      (CRT) devices. METHODS: The study examined 102 patients with CRT devices.
      Oversensing artifacts in the atrial channel were inspected on intracardiac
      electrograms, and their timing with respect to the beginning of QRS was
      determined during DDD-right ventricular (RV), DDD-LV, DDD-biventricular (BiV),
      and AAI pacing modes. The occurrence of ELT during DDD-LV pacing with a
      postventricular atrial refractory period (PVARP) of 250 ms was also assessed.
      RESULTS: The timing of oversensing artifacts (in relation to the beginning of
      surface QRS) was dependent on ventricular activation sequence, occurring promptly
      following intrinsic activation via the right bundle branch (47.1 +/- 26.4 ms),
      later during RV pacing (108.7 +/- 22.5 ms) or BiV pacing (109.4 +/- 23.1 ms), and
      significantly later, corresponding to the final part of the QRS, during LV pacing
      (209.6 +/- 40.0 ms, range: 140-340 ms, P < 0.001). Oversensing was significantly
      more frequent during LV than during RV pacing (35.3% vs 22.5%, P < 0.001). Far
      field ELT was observed in six patients. CONCLUSIONS: Oversensing artifacts in the
      atrial channel are likely caused by depolarization of the basal part of the right
      ventricle. The novel mechanism of QRS oversensing outside PVARP, caused by a
      reversed ventricular activation sequence during LV-only pacing, may be important
      in some CRT patients.

PMID- 21954968
TI  - The role of post-natal ontogeny in the evolution of phenotypic diversity in
      Podarcis lizards.
AB  - Understanding the role of the developmental pathways in shaping phenotypic
      diversity allows appreciating in full the processes influencing and constraining
      morphological change. Podarcis lizards demonstrate extraordinary morphological
      variability that likely originated in short evolutionary time. Using geometric
      morphometrics and a broad suite of statistical tests, we explored the role of
      developmental mechanisms such as growth rate change, ontogenetic
      divergence/convergence/parallelism as well as morphological expression of
      heterochronic processes in mediating the formation of their phenotypic diversity
      during the post-natal ontogeny. We identified hypermorphosis - the prolongation
      of growth along the same trajectory - as the process responsible for both
      intersexual and interspecific morphological differentiation. Albeit the common
      allometric pattern observed in both sexes of any species constrains and canalizes
      their cephalic scales variation in a fixed portion of the phenotypic space, the
      extended growth experienced by males and some species allows them to achieve
      peramorphic morphologies. Conversely, the intrasexual phenotypic diversity is
      accounted for by non-allometric processes that drive the extensive morphological
      dispersion throughout their ontogenetic trajectories. This study suggests a model
      of how simple heterochronic perturbations can produce phenotypic variation, and
      thus potential for further evolutionary change, even within a strictly
      constrained developmental pathway.

PMID- 21954969
TI  - Chemical constituents and their bioactivities of "Tongling White Ginger"
      (Zingiber officinale).
AB  - Gingerols and their corresponding dehydration products shogaols were considered
      as the active principles of ginger, the rhizome of the plant Zingiber officinale,
      for its antioxidant, anti-inflammatory, and antitumor activities. Ginger (Z.
      officinale) has been cultivated for thousands of years as a spice and for
      medicinal purposes in China. Tongling (Anhui province, China) has traditionally
      been regarded as an ideal cultivation place. "Tongling White Ginger" enjoys a
      reputation for being one of the top gingers in China for its thin white peel,
      tender flesh, rich juice, and flavor. In this study, we have isolated and
      identified two novel gingerdione dimers, bisgingerdiones A (1) and B (2); two new
      gingerol derivatives, (5R)-5-acetoxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptan-3
      one (3) and methyl (Z)-neral acetal-[6]-gingerdiol (4); and 38 known compounds (5
      42) from rhizomes of Zingiber officinale collected from Tongling, China. Their
      structures were elucidated by means of spectroscopic methods. Compounds 1-4
      showed weak cytotoxic and anti-HIV-1 activities. Compounds 6, 8, and 26 showed
      inhibitory activities against human and mouse 11beta-HSD1 (11beta-hydroxysteroid
      dehydrogenases) with IC(50) values between 1.09 and 1.30 MUM.

PMID- 21954970
TI  - Canine intracranial neoplasia: clinical risk factors for development of epileptic
      seizures.
AB  - OBJECTIVES: To identify clinical risk factors for seizures in dogs with
      intracranial neoplasia. METHODS: A cross-sectional retrospective study of 68 dogs
      with histopathologically confirmed primary or secondary intracranial neoplasia,
      complete clinical history and magnetic resonance imaging of the brain was
      conducted. Signalment and clinical history were retrieved from clinical records
      and magnetic resonance images of the brain were re-evaluated. Prevalence of
      findings was compared between dogs with and without seizures. RESULTS: Forty-two
      dogs had tumour-related seizures, the remaining 26 were seizure-free. Tumour
      types included meningioma (23 dogs with and 5 without seizures), glioma (9 dogs
      with and 6 without seizures), choroid plexus tumour (2 dogs without seizures),
      neuroblastoma (1 dog with seizures) and metastatic/invasive tumours including
      lymphoma (9 dogs with and 13 without seizures). On the basis of multi-variable
      logistic regression analysis, risk factors for seizures associated with
      intracranial neoplasia were magnetic resonance imaging findings consistent with
      the presence of neoplastic tissue in frontal lobe [odds ratio (OR) 9.61; 95%
      confidence interval (CI) 2.59 to 35.61], marked gadolinium enhancement (OR 10.41;
      95% CI 2.07 to 52.30) and magnetic resonance imaging findings of subfalcine
      and/or subtentorial herniation (OR 3.88; 95% CI 1.10 to 13.71). CLINICAL
      SIGNIFICANCE: Dogs with primary or secondary intracranial neoplasia are at risk
      of seizures, particularly those with tumours that affect the frontal lobe,
      enhance markedly with gadolinium, or cause subfalcine and/or subtentorial
      herniation.

PMID- 21954971
TI  - Towards developing a guideline for vocational evaluation following traumatic
      brain injury: the qualitative synthesis of clients' perspectives.
AB  - PURPOSE: This paper is a qualitative synthesis of clients' perspectives of the
      elements significant to return to work following traumatic brain injury (TBI).
      This is part of a larger review, completed to provide the evidence base for a
      vocational evaluation guideline. METHODS: Processes outlined in the Cochrane
      Handbook of Systematic Review guided the full review including: developing review
      questions, search strategies and selection criteria; quality appraisal; data
      extraction, analysis and synthesis; drawing conclusions. Four data bases (i.e.
      Medline, Embase, PsychInfo, Cochrane) were searched for relevant qualitative
      studies. Evidence tables were used to extract data from studies and thematic
      analysis employed to analyze the qualitative data. RESULTS: Analysis of clients'
      perspectives on return to work resulted in four key themes including the
      following: 1) meaning of work; 2) process of return to work and reconciling new
      identities; 3) opportunities to try versus risks of failure; 4) significance of
      supports. Themes are discussed in relation to vocational evaluation and findings
      from other syntheses. CONCLUSIONS: Vocation evaluation should include the
      assessment of: the meaning clients ascribe to work following a TBI and their post
      injury goals; clients' self-perceptions of work competency, work readiness and
      anticipated challenges with return to work; and the available supports.

PMID- 21954972
TI  - Mitochondrial thiols in antioxidant protection and redox signaling: distinct
      roles for glutathionylation and other thiol modifications.
AB  - SIGNIFICANCE: The mitochondrial matrix contains much of the machinery at the
      heart of metabolism. This compartment is also exposed to a high and continual
      flux of superoxide, hydrogen peroxide, and related reactive species. To protect
      mitochondria from these sources of oxidative damage, there is an integrated set
      of thiol systems within the matrix comprising the
      thioredoxin/peroxiredoxin/methionine sulfoxide reductase pathways and the
      glutathione/glutathione peroxidase/glutathione-S-transferase/glutaredoxin
      pathways that in conjunction with protein thiols prevent much of this oxidative
      damage. In addition, the changes in the redox state of many components of these
      mitochondrial thiol systems may transduce and relay redox signals within and
      through the mitochondrial matrix to modulate the activity of biochemical
      processes. RECENT ADVANCES: Here, mitochondrial thiol systems are reviewed, and
      areas of uncertainty are pointed out, focusing on recent developments in our
      understanding of their roles. CRITICAL ISSUES: The areas of particular focus are
      on the multiple, overlapping roles of mitochondrial thiols and on understanding
      how these thiols contribute to both antioxidant defenses and redox signaling.
      FUTURE DIRECTIONS: Recent technical progress in the identification and
      quantification of thiol modifications by redox proteomics means that many of the
      questions raised about the multiple roles of mitochondrial thiols can now be
      addressed.

PMID- 21954974
TI  - Reproductive behavior of individuals with increased risk of having a child with
      retinoblastoma.
AB  - To investigate reproductive behavior of individuals at increased risk of having a
      child with retinoblastoma (Rb), we conducted a cross-sectional questionnaire
      survey among 118 counselees visiting the Clinical Genetics Department of the
      National Rb Center in the Netherlands. The recurrence risk for counselees ranged
      from <1% to 50%. The response rate was 69%. Of 43 respondents considering having
      children after becoming aware of their increased risk, Rb influenced reproductive
      behavior for 25 (58%), of whom 14 had a recurrence risk <3%. Twenty of these 25
      decided against having more children and 5 used prenatal diagnosis. Eighteen of
      the 43 respondents did not use any of the alternative reproductive options and
      had children (or more children), although half indicated having had doubts about
      their decisions. Multiple logistic regression showed that only perceived risk (p
      = 0.003) was significantly associated with Rb influencing reproductive behavior.
      Of 17 respondents planning children (or more children), 11 (65%) considered using
      one of the alternative reproductive options. We conclude that reproductive
      behavior is greatly influenced by Rb and that perceived risk, not objective risk,
      is the most important factor of influence. It is important to offer individuals
      at increased risk continued access to genetic counseling, even when this risk is
      small.

PMID- 21954975
TI  - Short-term effects of a single intravitreal bevacizumab injection on retinal
      vessel calibre.
AB  - PURPOSE:   The aim was to investigate the short-term effects of a single
      intravitreal bevacizumab injection on the retinal vessel calibre in patients with
      neovascular age-related macular degeneration and in patients with diabetic
      macular oedema. METHODS:   Twelve patients with neovascular age-related macular
      degeneration and eight patients with diabetic macular oedema were included in the
      study. All patients received an intravitreal injection of 1.25 mg bevacizumab.
      Red-free fundus photographs (35 degrees ) were acquired with a fundus camera at
      baseline and one day, one week and one month after the intravitreal injection.
      Measurements of retinal vessel diameter were made of the supero-temporal retinal
      venule and arteriole using the software available on the IMAGEnet program.
      RESULTS:   Although there appeared to be a trend towards vasoconstriction for the
      measurements in the diabetic macular oedema group (both for arterioles and
      venules at day 7) and the age-related macular degeneration group (for venules at
      day 1 and for arterioles at day 7), it did not reach statistical significance (p
      > 0.05). Optical coherence tomography revealed a significant decrease in foveal
      thickness measurements in both groups at the one month visit compared with
      baseline. CONCLUSION:   The results suggest that intravitreal injection of
      bevacizumab might induce retinal vasoconstriction; however, low numbers of
      subjects might have prevented the difference from reaching statistical
      significance. Further studies with a larger number of subjects would reveal the
      effect of intravitreal anti-vascular endothelial growth factor treatment on
      retinal vessel diameters more clearly.

PMID- 21954976
TI  - Insertion of benzynes into the P?N Bond of P-alkenyl(alkynyl)-lambda5
      phosphazenes.
AB  - Benzynes, generated from 2-(trimethylsilyl)phenyl triflates, have been found to
      react with P-Alkenyl-lambda(5)-phosphazenes via a formal pi-insertion into the
      P?N bond. A subsequent retro [2 + 2] cycloaddition/6pi
      electrocyclization/protonation cascade explains the formation of the resulting
      1,4-benzazaphosphorinium triflates. P-Alkynyl lambda(5)-phosphazenes and
      phosphane sulfides undergo similar transformations.

PMID- 21954973
TI  - Alzheimer CSF biomarkers in routine clinical setting.
AB  - OBJECTIVES: Our work was aimed to evaluate Alzheimer's disease diagnosis
      improvement using cerebrospinal fluid biomarkers (CSF) in neurological daily
      practice. MATERIALS AND METHODS: For this purpose, 150 patients clinically and
      neurochemically classified as having AD or cognitive impairment with or without
      other dementia type were included in the study. The following CSF peptides were
      studied, blindly to the clinical diagnosis: beta-amyloid(1-42) peptide (Abeta(1
      42)), Tau (T-tau), threonine-181 hyperphosphorylated tau protein (P-tau(181)),
      and beta-amyloid(1-40) peptide (Abeta(1-40)). From these measurements,
      Innotest(r) Amyloid Tau Index (IATI) was calculated for each patient. RESULTS:
      This assessment allowed to separate 83 biochemical profiles of AD and 67 non
      Alzheimer's disease (non-AD), both AD and non-AD categories match with clinical
      data amounting to 73% and 90%, respectively. Among mild cognitive impairment
      (MCI) patients, CSF biomarkers led to discriminate those who are likely to be AD.
      We devoted a special section to Abeta(1-40) which is not a routine parameter but
      can help to confirm a pathological amyloid process as Abeta(1-42)/Abeta(1-40)
      ratio underlining the real decline of the Abeta(1-42). CONCLUSIONS: The interest
      of biomarkers and their ability to solve awkward cases were carefully noticed all
      the more when a discrepancy between clinical and CSF biological data was
      involved. The final proposed algorithm allowed to identify pathogenic forms of AD
      according to the prevailing role of hyperphosphorylated tau or amyloid beta
      peptide.

PMID- 21954977
TI  - On-demand electrochemical activation of the click reaction on self-assembled
      monolayers on gold presenting masked acetylene groups.
AB  - We report on a new surface modification method for grafting a "dynamic" property
      for on-demand activation of the click reaction. Our approach utilizes the
      acetylene group masked with dicobalt hexacarbonyl, Co(2)(CO)(6), which is not
      reactive toward the click reaction. Electrochemical treatment reveals the
      acetylene group on the selected region, which is then used as a chemical handle
      for surface functionalization via the click reaction with an azide-containing
      molecule. Electrochemical and chemical conversions on the surface were verified
      by cyclic voltammetry, X-ray photoelectron spectroscopy, and fluorescence
      spectroscopy. We have demonstrated immobilization of an azide-modified RGD
      peptide and promotion of cell adhesion/migration to the region of electrochemical
      induction.

PMID- 21954978
TI  - Do components of current 'hardcore smoker' definitions predict quitting
      behaviour?
AB  - AIMS: It has been hypothesized that the smoking population is represented by an
      increasingly 'hardcore' group of smokers who are resistant to quitting. Many
      definitions of 'hardcore smokers' have been used, but their predictive validity
      is unknown. To evaluate whether 'hardcore smoker' definition components predict
      quitting behaviours and which combinations of 'hardcore' components are most
      predictive. DESIGN, SETTING AND PARTICIPANTS: Longitudinal, random telephone
      survey of a representative sample of adult smokers in Ontario, Canada (n = 4130,
      recruited 2005-08 and followed for 1 year). MEASUREMENTS: Multiple logistic
      regression models were compared to evaluate the predictive ability of 'hardcore'
      components (high daily cigarette consumption, high nicotine dependence, being a
      daily smoker, history of long-term smoking, no quit intention and no life-time
      quit attempt) on three outcomes [continued smoking, not attempting to quit and
      having unsuccessful quit attempt(s)]. FINDINGS: All 'hardcore' components
      predicted having no quit attempt and continued smoking during follow-up (P <
      0.05), except for history of long-term smoking and no life-time quit attempt (for
      continued smoking). Among respondents who made 1 + quit attempts during follow
      up, only high nicotine dependence, high daily cigarette consumption and being a
      daily smoker were predictive of quitting failure (P < 0.01). The best combination
      of components depended on the outcome. CONCLUSIONS: Measures of 'hardcore'
      include a mixture of motivational, dependence and behavioural variables. As found
      previously, motivational and behavioural measures, such as intention to quit,
      predict failure to make quit attempts. However, dependence components best
      predicted continued smoking and thus would be best for further exploring the
      hardening hypothesis.

PMID- 21954979
TI  - Computational studies on structural and excited-state properties of modified
      chlorophyll f with various axial ligands.
AB  - Time-dependent density functional theory (TDDFT) calculations have been used to
      understand the excited-state properties of modified chlorophyll f (Chlide f),
      Chlide a, Chlide b, and axial ligated (with imidazole, H(2)O, CH(3)OH, CH(3)COOH,
      C(6)H(5)OH) Chlide f molecules. The computed differences among the Q(x), Q(y),
      B(x), and B(y) band absorbance wavelengths of Chlide a, b, and f molecules are
      found to be comparable with the experimentally observed shifts for these bands in
      chlorophyll a (chl a), chl b, and chl f molecules. Our computations provide
      evidence that the red shift in the Q(y) band of chl f is due to the extended
      delocalization of macrocycle chlorin ring because of the presence of the -CHO
      group. The local contribution from the -CHO substituent to the macrocycle chlorin
      ring stabilizes the corresponding molecular orbitals (lowest unoccupied molecular
      orbital (LUMO) of the Chlide f and LUMO-1 of the Chlide b). All the absorption
      bands of Chlide f shift to higher wavelengths on the addition of axial ligands.
      Computed redox potentials show that, among the axial ligated Chlide f molecules,
      Chlide f-imidazole acts as a good electron donor and Chlide f-CH(3)COOH acts as a
      good electron acceptor.

PMID- 21954980
TI  - The 12th meeting of the Diabetes in Pregnancy Study Group of North America (DPSG
      NA): introduction and overview.
AB  - The Diabetes in Pregnancy Study Group of North America (DPSG-NA) held its 12th
      meeting April 1-2, 2011 in Washington DC. The meeting, which was co-hosted by the
      Washington Hospital Center and the University of Maryland School of Medicine
      focused on five broad themes: (i) the prevention of diabetes and its risk
      factors, such as obesity, in pregnancy; (ii) the appropriate use of
      pharmacotherapies for managing diabetes in pregnancy; (iii) optimal glycemic
      control; (iv) the value of nutrition, exercise and limiting weight gain during
      pregnancy and (v) the diagnosis and consequences of diabetic fetopathy. These
      proceedings reflect peer-reviewed papers of data presented at the meeting. Time
      also was allocated to discuss the perceived barriers to using the one-step, 75 g
      oral glucose tolerance test as the first-line approach to diagnosing gestational
      diabetes mellitus. Responses from a survey of participants on perceived barriers
      to adopting this method into widespread clinical practice are discussed.

PMID- 21954981
TI  - A nonclassical dihydrogen adduct of S = 1/2 Fe(I).
AB  - We have exploited the capacity of the "(SiP(iPr)(3))Fe(I)" scaffold to
      accommodate additional axial ligands and characterized the mononuclear S = 1/2
      H(2) adduct complex (SiP(iPr)(3))Fe(I)(H(2)). EPR and ENDOR data, in the context
      of X-ray structural results, revealed that this complex provides a highly unusual
      example of an open-shell metal complex that binds dihydrogen as a ligand. The
      H(2) ligand at 2 K dynamically reorients within the ligand-binding pocket,
      tunneling among the energy minima created by strong interactions with the three
      Fe-P bonds.

PMID- 21954982
TI  - Natural history of older adults with impaired kidney function: the InCHIANTI
      study.
AB  - The aim of this study was to assess the kidney function of an older community
      dwelling population at baseline and appraise its evolution after 3 years of
      follow-up in terms of chronic kidney disease (CKD) stage progression, magnitude
      of glomerular filtration rate (GFR) changes, and value of serum creatinine. This
      was a prospective population-based study of 676 Italian participants, aged 65
      years and older. GFR was estimated using the Cockcroft-Gault equation and the
      Modification of Diet in Renal Disease Study equation. Using the Cockcroft-Gault
      equation. A total of 33% of participants had criteria of CKD (GFR < 60 mL/min) at
      baseline; among them, the majority remained stable, 10% improved, and 7%
      progressed to more severe CKD stages at follow-up. Loss of GFR in participants
      with GFR < 60 mL/min was significantly lower (1.4 mL/min per year) than in
      participants with GFR >= 60 mL/min (3.3 mL/min per year) at baseline. Most
      participants classified with CKD stage 2 (GFR 60-89 mL/min) or stage 3 (GFR 30-59
      mL/min) at baseline did not change stage, whereas 55% of people with CKD stage 1
      (GFR > 90 mL/min) at baseline worsened to stage 2 and 10% worsened to stage 3. An
      abnormal high level of serum creatinine at baseline did not help to predict who
      might worsen at follow-up. Older people with CKD displayed a low progression of
      renal disease and therefore are at higher risk for co-morbidities related to CKD
      than for progression to end-stage renal disease.

PMID- 21954983
TI  - Rest-activity patterns in patients with delirium.
AB  - OBJECTIVE: Delirium is a frequent syndrome in elderly hospital patients. Symptoms
      typically show a fluctuating course during the day, with patients exhibiting
      disturbances of their sleep-wake rhythm. Delirium is frequently underdiagnosed,
      especially the so-called hypoactive subtype. Devices measuring 24-hr motor
      patterns could contribute to the recognition of delirium. The purpose of this
      paper is two-fold. First, the results of a pilot study are presented, in which 24
      hr motor patterns of delirious patients are measured with a wrist-actigraph.
      Second, studies reporting 24-hr motor patterns in delirious patients are
      systematically reviewed. METHODS: The pilot study included 9 patients, 65 years
      or older, with a hip fracture in need of surgical repair. For the review, MEDLINE
      and Embase were searched for studies on motor activity assessment in delirious
      patients. RESULTS: In the pilot study, the 24-hr activity rhythm was severely
      disturbed during delirium, and most actigraphic sleep parameter estimates
      indicated significantly worse sleep during delirious nights. The systematic
      search resulted in 10 papers. In 3 papers, the sleep-wake rhythm of delirious
      patients was significantly different from that of nondelirious patients. In 5
      papers, delirious patients could be classified into delirium subtypes. In the 2
      remaining papers, 24-hr motor patterns of delirium subtypes were not
      significantly different. CONCLUSION: Activity patterns revealed differences
      between delirious and nondelirious patients and between the different subtypes,
      even in small samples of patients. Future studies, with preferably larger sample
      sizes, should confirm the potential of activity pattern measuring devices in the
      early detection of delirium.

PMID- 21954984
TI  - Transplantation of solid organs procured from influenza A H1N1 infected donors.
AB  - Following the influenza A H1N1 (swine flu) pandemic, there remains little
      evidence informing the safety of transplanting organs from donors suspected or
      diagnosed with H1N1. Limited guidelines from the major transplant societies leave
      the use of such organs at the discretion of individual transplant centres, and
      practice varies considerably both nationally and internationally. We present the
      largest published series of outcome following transplantation of organs from H1N1
      positive donors and demonstrate that these organs can be transplanted safely and
      with good short-term outcome. We discuss our local policy for treatment of
      recipients with Oseltamivir.

PMID- 21954985
TI  - Economic burden of chronic obstructive pulmonary disease.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to estimate the direct
      medical costs of COPD in two public health clusters in Singapore from 2005 to
      2009. METHODS: Patients aged 40 years and over, who had been diagnosed with COPD,
      were identified in a Chronic Disease Management Data-mart. Annual utilization of
      health services in inpatient, specialist outpatient, emergency department and
      primary care settings was extracted from the Chronic Disease Management Data
      mart. Trends in attributable costs, proportions of costs and health-care
      utilization were analyzed across each level of care. A weighted attribution
      approach was used to allocate costs to each health-care utilization episode,
      depending on the relevance of co-morbidities. RESULTS: The mean total cost was
      approximately $9.9 million per year. Inpatient admissions were the major cost
      driver, contributing an average of $7.2 million per year. The proportion of
      hospitalization costs declined from 75% in 2005 to 68% in 2009. Based on the 5
      year average, attendances at primary care clinics, emergency department and
      specialist clinics contributed 3%, 5% and 17%, respectively, of overall COPD
      costs. On average, 42% of the total cost burden was incurred for the medical
      management of COPD. The share of cost incurred for the treatment of conditions
      related and unrelated to COPD were 29% and 26%, respectively, of the total
      average costs. CONCLUSIONS: COPD is likely to represent a significant burden to
      the public health system in most countries. The findings are particularly
      relevant to understanding the allocation of health-care resources and informing
      appropriate cost containment strategies.

PMID- 21954986
TI  - Maternal control of seed oil content in Brassica napus: the role of silique wall
      photosynthesis.
AB  - Seed oil content is an important agronomic trait in rapeseed. However, our
      understanding of the regulatory processes controlling oil accumulation is still
      limited. Using two rapeseed lines (zy036 and 51070) with contrasting oil content,
      we found that maternal genotype greatly affects seed oil content. Genetic and
      physiological evidence indicated that difference in the local and tissue-specific
      photosynthetic activity in the silique wall (a maternal tissue) was responsible
      for the different seed oil contents. This effect was mimicked by in planta
      manipulation of silique wall photosynthesis. Furthermore, the starch content and
      expression of the important lipid synthesis regulatory gene WRINKLED1 in
      developing seeds were linked with silique wall photosynthetic activity. 454
      pyrosequencing was performed to explore the possible molecular mechanism for the
      difference in silique wall photosynthesis between zy036 and 51070. Interestingly,
      the results suggested that photosynthesis-related genes were over-represented in
      both total silique wall expressed genes and genes that were differentially
      expressed between genotypes. A potential regulatory mechanism for elevated
      photosynthesis in the zy036 silique wall is proposed on the basis of knowledge
      from Arabidopsis. Differentially expressed ribulose-1,5-bisphosphate
      carboxylase/oxygenase (Rubisco)-related genes were used for further
      investigations. Oil content correlated closely with BnRBCS1A expression levels
      and Rubisco activities in the silique wall, but not in the leaf. Taken together,
      our results highlight an important role of silique wall photosynthesis in the
      regulation of seed oil content in terms of maternal effects.

PMID- 21954987
TI  - Spindle cell squamous cell carcinoma not expressing stratified but simple
      epithelial cytokeratin: efficacy of simple epithelial cytokeratin
      immunoreactivity.
AB  - We present two cases of spindle cell squamous cell carcinoma, which were derived
      from solar keratosis and burn scar in two elderly Japanese patients,
      respectively. The tumors involved the whole dermis and subcutis in connection
      with the overlying epidermis. They were composed mainly of anaplastic spindle
      cells partially forming storiform patterns. The tumor cells were diffusely
      positive for vimentin and cytokeratin 8/18 (clone CAM5.2, simple epithelial
      cytokeratin), but negative for cytokeratin 1/5/10/14 (clone 34betaE12, stratified
      epithelial cytokeratin). Ultrastructural analysis of a patient demonstrated
      desmosomes and tonofilaments in the tumor cells. Although spindle cell squamous
      cell carcinoma is usually positive for vimentin, detailed cytokeratin profile is
      controversial. The present cases revealed immunohistochemistry not expressing
      stratified but simple epithelial cytokeratin and vimentin. We should be reminded
      of the efficacy of simple epithelial cytokeratin immunoreactivity in spindle cell
      squamous cell carcinoma.

PMID- 21954989
TI  - Dual ventricular response: what is the mechanism?

PMID- 21954988
TI  - A brief primer on sleep for pediatric and child clinical neuropsychologists.
AB  - Sleep problems are common in the children seen by pediatric and child clinical
      neuropsychologists, and these problems have the potential to significantly impact
      the child and his or her family. All are treatable to some degree, and some
      respond extremely well to existing treatments. This article provides a brief
      overview of the impact, nature, screening, and treatment for childhood sleep
      problems, with a particular emphasis on issues relevant to practicing
      neuropsychologists.

PMID- 21954990
TI  - Silver-Russell syndrome due to maternal uniparental disomy 7 and a familial
      reciprocal translocation t(7;13).
AB  - Silver-Russell syndrome (SRS) is a genetically heterogeneous disorder
      characterized by intrauterine and postnatal growth retardation, typical facial
      features and a spectrum of additional features including body and limb asymmetry
      and clinodactyly. Maternal uniparental disomy for chromosome 7 (upd(7)mat) was
      shown to occur in 5-10% of patients with SRS. Maternal UPD7 is clinically often
      associated with mild SRS. Parents of an affected child are given a negligible
      recurrence risk as all reported cases with upd(7)mat have been sporadic so far.
      In general, chromosomal rearrangements-like translocations increase the
      likelihood of uniparental disomy (UPD) for the chromosomes involved. However, SRS
      as the result of a upd(7)mat in association with an inherited chromosomal
      translocation involving chromosome 7 has only been reported once before. Here, we
      describe the second case of SRS with upd(7)mat due to a familial reciprocal
      translocation t(7;13). This emphasizes the importance of chromosome analysis in
      SRS patients with upd(7)mat to rule out chromosomal rearrangements despite their
      rare occurrence as they are of great relevance for genetic counseling of SRS
      families.

PMID- 21954991
TI  - Real-time 4-D radiotherapy for lung cancer.
AB  - Respiratory motion considerably influences dose distribution, and thus clinical
      outcomes in radiotherapy for lung cancer. Breath holding, breath coaching,
      respiratory gating with external surrogates, and mathematical predicting models
      all have inevitable uncertainty due to the unpredictable variations of internal
      tumor motion. The amplitude of the same tumor can vary with standard deviations >
      5 mm occurring in 23% of T1-2N0M0 non-small cell lung cancers. Residual motion
      varied 1-6 mm (95th percentile) for the 40% duty cycle of respiratory gating with
      external surrogates. The 4-D computed tomography is vulnerable to problems
      relating to the external surrogates. Real-time 4-D radiotherapy (4DRT), where the
      temporal changes in anatomy during the delivery of radiotherapy are explicitly
      considered in real time, is emerging as a new method to reduce these known
      sources of uncertainty. Fluoroscopic, real-time tumor-tracking technology using
      internal fiducial markers near the tumor has +/- 2 mm accuracy, and has achieved
      promising clinical results when used with X-ray therapy. Instantaneous
      irradiation based on real-time verification of internal fiducial markers is
      considered the minimal requisite for real-time 4DRT of lung cancers at present.
      Real-time tracking radiotherapy using gamma rays from positron emitters in tumors
      is in the preclinical research stage, but has been successful in experiments in
      small animals. Real-time tumor tracking via spot-scanning proton beam therapy has
      the capability to cure large lung cancers in motion, and is expected to be the
      next-generation real-time 4DRT.

PMID- 21954992
TI  - A meta-analysis of the comparative efficacy of ablation for atrial fibrillation
      with and without ablation of the ganglionated plexi.
AB  - BACKGROUND: Ganglionated plexi (GP) is claimed to be potentially responsible for
      atrial fibrillation (AF). The efficacy and safety of GP ablation remains
      controversial. This meta-analysis aimed to assess the efficacy of procedure with
      or without ablation of GP. METHODS AND RESULTS: We included controlled clinical
      trials or randomized controlled trials comparing procedures of GP ablation plus
      pulmonary vein isolation (PVI), GP ablation plus Maze, or GP ablation alone
      (experimental arm), with PVI or Maze without GP ablation (control arm). The early
      episodes of atrial arrhythmia recurrence (early recurrence) and freedom from AF
      (primary efficacy endpoint) were estimated. Six trials with a total of 342
      patients (172 per experimental arm, 170 per control arm) were included in the
      meta-analysis. Subgroup analysis demonstrated that there was no significant
      difference in early recurrence between additional GP ablation to PVI or Maze, and
      PVI or Maze without ablation of GP (P = 0.06). However, early recurrence was
      significantly higher after GP ablation alone, compared with PVI alone (P = 0.02).
      Freedom from AF recurrence was significantly improved by additional GP ablation
      to PVI and Maze, compared with PVI and Maze without ablation of GP (P < 0.01).
      However, it was significantly aggravated by GP ablation alone, compared with PVI
      alone (P = 0.006). CONCLUSION: The short and relatively long-term success rate of
      additional GP ablation to PVI or Maze is superior to PVI or Maze without ablation
      of GP. GP ablation alone is less effective than PVI alone for the treatment of
      AF. Future studies are necessary to establish and standardize the targeting
      sites, endpoints, and methods of GP ablation.

PMID- 21954993
TI  - Hepatic artery reconstruction and successful management of its complications in
      living donor liver transplantation using a right lobe.
AB  - BACKGROUND: The aim of the present study was to improve the techniques of hepatic
      artery (HA) reconstruction and to properly manage arterial complications after
      living donor liver transplantation (LDLT). METHODS: Prospectively collected data
      collected from 371 patients who underwent adult LDLT using a right lobe from
      January 2000 to August 2009 were retrospectively reviewed. RESULTS: Of 17
      patients (4.6%, 17/371) with double HA stumps in the graft, 12 patients (70.6%)
      received dual HA reconstruction. HA complications were composed of thrombosis (n
      = 6), pseudoaneurysm (n = 2), and stenosis (n = 4), showing 3.2% (12/371) of
      incidence. In patients with HA thrombosis, whereas operative thrombectomies with
      re-anastomosis rescued all the grafts in early attack (n = 3, <=1 wk),
      angiographic thrombolysis successfully reestablished the flow in patients with
      late attack (n = 3, >1 wk). In all patients with HA complications, except for
      one, all of our treatment modalities - operation and angiographic intervention -
      resulted in successful rescue of grafts and no patient received re
      transplantation because of HA complications. CONCLUSION: Prompt diagnosis of HA
      complications by serial post-operative Doppler ultrasound and corresponding
      treatment strategies, including operative and radiological intervention, can
      rescue both grafts and patients without necessitating re-transplantation.

PMID- 21954994
TI  - Triglycerides as an early pathophysiological marker of endothelial dysfunction in
      nondiabetic women with a previous history of gestational diabetes.
AB  - OBJECTIVE: To investigate whether baseline triglyceride levels are associated
      with early glucose dysregulation and/or cardiovascular risk in women with a
      previous history of gestational diabetes. DESIGN: Prospective postpregnancy
      cohort study. SETTING: Polish university hospitals. SAMPLE: Participants included
      125 women with previous gestational diabetes and 40 women with normal glucose
      regulation during pregnancy. METHODS: All women were studied 2-24 months (mean 12
      +/- 10 months) after the index pregnancy. Women with previous gestational
      diabetes were divided into tertiles in accordance with baseline triglyceride
      levels. MAIN OUTCOME MEASURES: We assessed glucose regulation (oral glucose
      tolerance test), insulin resistance (homeostasis model assessment), markers of
      endothelial dysfunction (soluble: intercellular adhesion molecule-1, vascular
      cell adhesion molecule-1, E-selectin, tissue plasminogen activator antigen, von
      Willebrand factor antigen), fibrinolysis (plasminogen activator inhibitor
      antigen), inflammation (high-sensitivity C-reactive protein) and lipid levels.
      RESULTS: Women with previous gestational diabetes (78% normal glucose regulation,
      22% impaired glucose tolerance) had a high cardiometabolic risk profile compared
      with control women (100% normal glucose regulation). Baseline triglycerides >0.83
      mmol/l were associated with a higher prevalence of impaired glucose tolerance,
      higher high-sensitivity C-reactive protein and triglyceride/high-density
      lipoprotein-cholesterol ratio. Triglycerides >1.22 mmol/l were associated with
      higher body fat indexes, higher insulin resistance, higher levels of endothelial
      dysfunction biomarkers, higher plasminogen activator inhibitor antigen and
      dyslipidemia. Only E-selectin was independently associated with triglyceride
      levels. CONCLUSIONS: Baseline triglyceride levels are a cardiovascular risk
      marker as well as a pathophysiological parameter independently associated with
      endothelial dysfunction in nondiabetic women with previous gestational diabetes
      at 2-24 months after an index pregnancy. Normalization of triglycerides should be
      included in preventive therapy after a pregnancy complicated by gestational
      diabetes.

PMID- 21954995
TI  - Body weight supported treadmill training versus traditional training in patients
      dependent on walking assistance after stroke: a randomized controlled trial.
AB  - PURPOSE: Treadmill training with body weight support (TTBWS) for relearning
      walking ability after brain damage is an approach under current investigation.
      Efficiency of this method beyond traditional training is lacking evidence,
      especially in patients needing walking assistance after stroke. The objective of
      this study was to investigate change in walking and transfer abilities, comparing
      TTBWS with traditional walking training. METHODS: A single-blinded, randomized
      controlled trial was conducted. Sixty patients referred for multi-disciplinary
      primary rehabilitation were assigned into one of two intervention groups, one
      received 30 sessions of TTBWS plus traditional training, the other traditional
      training alone. Daily training was 1 hr. Outcome measures were Functional
      Ambulation Categories (FAC), Walking, Functional Independence Measure (FIM);
      shorter transfer and stairs, 10 m and 6-min walk tests. RESULTS: Substantial
      improvements in walking and transfer were shown within both groups after 5 and 11
      weeks of intervention. Overall no statistical significant differences were found
      between the groups, but 12 of 17 physical measures tended to show improvements in
      favour of the treadmill approach. CONCLUSIONS: Both training strategies provided
      significant improvements in the tested activities, suggesting that similar
      outcomes can be obtained in the two modalities by systematic, intensive and goal
      directed training.

PMID- 21954996
TI  - Amplified analysis of DNA by the autonomous assembly of polymers consisting of
      DNAzyme wires.
AB  - A systematic study of the amplified optical detection of DNA by Mg(2+)-dependent
      DNAzyme subunits is described. The use of two DNAzyme subunits and the respective
      fluorophore/quencher-modified substrate allows the detection of the target DNA
      with a sensitivity corresponding to 1 * 10(-9) M. The use of two functional
      hairpin structures that include the DNAzyme subunits in a caged, inactive
      configuration leads, in the presence of the target DNA, to the opening of one of
      the hairpins and to the activation of an autonomous cross-opening process of the
      two hairpins, which affords polymer DNA wires consisting of the Mg(2+)-dependent
      DNAzyme subunits. This amplification paradigm leads to the analysis of the target
      DNA with a sensitivity corresponding to 1 * 10(-14) M. The amplification mixture
      composed of the two hairpins can be implemented as a versatile sensing platform
      for analyzing any gene in the presence of the appropriate hairpin probe. This is
      exemplified with the detection of the BRCA1 oncogene.

PMID- 21954997
TI  - Core-extended terrylene tetracarboxdiimide: synthesis and chiroptical
      characterization.
AB  - The novel 1,16:6,7:8,9:14,15-tetranaphthoterrylene tetracarboxdiimide was
      synthesized via a straightforward route, yielding optically active atropisomers
      with a high racemization barrier. Absorption, fluorescence, and circular
      dichroism measurements revealed high absorption coefficients and fluorescence
      quantum yields and enabled the stereochemical assignment in combination with
      quantum mechanical calculations.

PMID- 21954998
TI  - The role of teosinte glume architecture (tga1) in coordinated regulation and
      evolution of grass glumes and inflorescence axes.
AB  - * Hardened floral bracts and modifications to the inflorescence axis of grasses
      have been hypothesized to protect seeds from predation and/or aid seed dispersal,
      and have evolved multiple times independently within the family. Previous studies
      have demonstrated that mutations in the maize (Zea mays ssp. mays) gene teosinte
      glume architecture (tga1) underlie a reduction in hardened structures, yielding
      free fruits that are easy to harvest. It remains unclear whether the causative
      mutation(s) occurred in the cis-regulatory or protein-coding regions of tga1, and
      whether similar mutations in TGA1-like genes can explain variation in the
      dispersal unit in related grasses. * To address these questions TGA1-like genes
      were cloned and sequenced from a number of grasses and analyzed phylogenetically
      in relation to morphology; protein expression was investigated by
      immunolocalization. * TGA1-like proteins were expressed throughout the spikelet
      in the early development of all grasses, and throughout the flower of the grass
      relative Joinvillea. Later in development, expression patterns differed between
      Tripsacum dactyloides, maize and teosinte (Z. mays ssp. parviglumis). * These
      results suggest an ancestral role for TGA1-like genes in early spikelet
      development, but do not support the hypothesis that TGA1-like genes have been
      repeatedly modified to affect glume and inflorescence axis diversification.

PMID- 21954999
TI  - A damage/benefit evaluation of addictive product use.
AB  - AIMS: To obtain damage/benefit assessments of eight commonly used addictive
      products and one addictive behaviour from French addiction experts and link these
      to overall evaluations. DESIGN AND SETTING: Criteria-based evaluation by experts
      in addiction. Specific statistical modelling to estimate the relative
      contribution of various criteria to formulating expert general opinion on
      products. PARTICIPANTS: Forty-eight French experts in addiction. MEASUREMENTS:
      Twelve criteria covering the whole spectrum of damages and benefits to users and
      to society evaluated using visual analogue scales (VAS). Direct measure of expert
      overall subjective opinions on products from user and from social perspectives.
      FINDINGS: Damage scoring identified alcohol (damage score = 48.1), heroin (damage
      score = 44.9) and cocaine (damage score = 38.5) as the most harmful products to
      users and to society; gambling was considered the least harmful (score = 22.5),
      replicating previous results. Damage scoring correlated poorly with legal status
      or with overall subjective expert opinions of products. Benefit perception scores
      indicated alcohol as a clear outlier (benefit score = 45.5) followed by tobacco
      (benefit score = 34.3) and cannabis (benefit score = 31.1). Statistical modelling
      suggested that experts attributed 10 times more importance to benefit perception
      than to damages when making their subjective opinion from a user perspective and
      two times more importance to benefit perception than to damages in formulating
      their opinion from a social perspective. CONCLUSIONS: The perceived benefits of
      addictive products appear to have a major impact on the opinion of those products
      expressed by a number of French addiction experts.

PMID- 21955000
TI  - A long white line.

PMID- 21955001
TI  - Nurse planner roles and functions.
AB  - The responsibilities of a nurse planner are crucial to the creation and
      development of both accredited and approved continuing education activities. The
      nurse planner serves as a repository for accreditation criteria and is charged
      with the oversight of identifying learning needs, identifying content experts,
      developing content and teaching strategies, and designing evaluation
      methodologies for activities that carry contact hour credit. This column
      describes the components of the role and identifies ways they can be
      operationalized.

PMID- 21955002
TI  - Emotional intelligence: it's more than IQ.
AB  - Emotional intelligence (EI) can determine the quality of our relationship with
      ourselves and others. Whether we are students, teachers, or managers or are in
      the clinical arena, EI influences our stress level, our ability to perform, and
      our effectiveness when working with others.

PMID- 21955003
TI  - Addressing innovation: changes in the American nurses credentialing center
      accreditation system.
AB  - In 2010 to 2011, the American nurses credentialing center accreditation system
      for continuing nursing education is undergoing major changes to increase the
      effectiveness, efficiency, and quality of the continuing education provided by
      accredited organizations and ultimately to improve patient care. This article
      highlights national drives that provide supportive evidence for program changes.

PMID- 21955004
TI  - The impact of pre-pregnancy body mass index on the risk of gestational diabetes.
AB  - OBJECTIVE: To evaluate the effect of pre-pregnancy body mass index (BMI) on the
      risk of developing gestational diabetes mellitus (GDM) in a large unselected
      population. METHODS: We performed a case control study using data collected in
      The Consortium on Safe Labor database. The association between BMI and GDM was
      evaluated both using BMI weight categories adopted by the National Institute of
      Health, and separately using BMI as a continuous variable. Multiple logistic
      regression analyses were used to evaluate the effects of BMI, age, ethnicity,
      parity, chronic hypertension and antenatal steroid use on the risk of GDM. Odds
      ratios (ORs) and 95% confidence intervals (CIs) were calculated to approximate
      relative risks of GDM. A p value of <0.05 was considered significant. RESULTS:
      After controlling for other factors, the risk of GDM increased with an increasing
      BMI across all weight categories. For each 1 kg/m(2) increase of BMI the OR of
      developing GDM was 1.08 (95% CI 1.08-1.09) and for each 5 kg/m(2) increase, the
      OR was 1.48 (95% CI 1.45-1.51). CONCLUSIONS: GDM is a multifactorial disorder and
      pre-pregnancy BMI plays an important role in that risk. Modest changes in pre
      pregnancy BMI may decrease the risk of GDM substantially.

PMID- 21955005
TI  - Enantioselective intramolecular [2 + 2]-photocycloaddition reactions of 4
      substituted quinolones catalyzed by a chiral sensitizer with a hydrogen-bonding
      motif.
AB  - Six 2-quinolones, which bear a terminal alkene linked by a three- or four
      membered tether to carbon atom C4 of the quinolone, were synthesized and
      subjected to an intramolecular [2 + 2]-photocycloaddition. The reaction delivered
      the respective products in high yields (78-99%) and with good regioselectivity in
      favor of the straight isomer. If conducted in the presence of a chiral hydrogen
      bonding template (2.5 equiv) at low temperature in toluene as the solvent, the
      reaction proceeded enantioselectively (83-94% ee). An organocatalytic reaction
      was achieved when employing a chiral hydrogen-bonding template with an attached
      sensitizing unit (benzophenone or xanthone). The xanthone-based organocatalyst
      proved to be superior as compared to the respective benzophenone. Closer
      inspection revealed that the reaction of 4-(pent-4-enyloxy)quinolone leading to a
      six-membered ring, annelated to the cyclobutane, was less enantioselective (up to
      41% ee with 30 mol % catalyst) than the reaction of 4-(but-3-enyloxy)quinolone
      leading to a five-membered ring (90% ee with 5 mol % and 94% ee with 20 mol %
      catalyst). Photophysical data (emission spectra, laser flash photolysis
      experiments) proved that the latter photocycloaddition was significantly faster,
      supporting the idea that the dissociation of the substrate from the catalyst
      prior to the photocycloaddition is responsible for the decreased
      enantioselectivity. Under optimized conditions, employing 10 mol % of the
      xanthone-based organocatalyst at -25  degrees C in trifluorotoluene as the
      solvent, three of the other four substrates gave the intramolecular [2 + 2]
      photocycloaddition products with high enantioselectivities (72-87% ee). In all
      catalyzed reactions, the yields based on conversion were moderate to good (40
      93%).

PMID- 21955006
TI  - Do wound complications or lymphoceles occur more often in solid organ transplant
      recipients on mTOR inhibitors? A systematic review of randomized controlled
      trials.
AB  - mTOR inhibitors have been associated with wound complications and lymphoceles. We
      systematically reviewed randomized controlled trials (RCTs) to compare these
      outcomes for solid organ transplant recipients. Relevant medical databases were
      searched to identify RCTs in solid organ transplantation comparing mTOR
      inhibitors with an alternative therapy reporting on wound complications and/or
      lymphoceles. Methodological quality of RCTs was assessed. Pooled analyses were
      performed to calculate odds ratios (OR) and 95% confidence intervals (CI). Thirty
      seven RCTs in kidney, heart, simultaneous pancreas-kidney and liver
      transplantation were included. Pooled analyses showed a higher incidence of wound
      complications (OR 1.77, CI 1.31-2.37) and lymphoceles (OR 2.07, CI 1.62-2.65) for
      kidney transplant recipients on mTOR inhibitors together with calcineurin
      inhibitors (CNIs). There was also a higher incidence of wound complications (OR
      3.00, CI 1.61-5.59) and lymphoceles (OR 2.13, CI 1.57-2.90) for kidney transplant
      recipients on mTOR inhibitors together with antimetabolites. Heart transplant
      patients receiving mTOR inhibitors together with CNIs also reported more wound
      complications (OR 1.82, CI 1.15-2.87). We found a higher incidence of wound
      complications and lymphoceles after kidney transplantation and a higher incidence
      of wound complications after heart transplantation for immunosuppressive regimens
      that included mTOR inhibitors from the time of transplantation.

PMID- 21955007
TI  - Bosentan for digital ulcers in patients with systemic sclerosis.
AB  - Recurrent digital ulcers are manifestations of vascular disease in patients with
      systemic sclerosis (SSc). We report six patients with severe digital ulcers who
      were treated with bosentan administered p.o., 62.5-125 mg daily. The mean
      duration from the diagnosis of SSc to the initiation of bosentan was 9.5 years,
      and the observation period after bosentan administration was from 7 months to 4.5
      years. In case 1, neither new digital ulcers nor Raynaud's phenomenon developed
      for 4.5 years. In case 2, digital ulcers recurred after the discontinuation of
      bosentan; however, re-administration of bosentan lead to the improvement. In
      cases 3-5 with recurrent digital ulcers, no new lesions have developed. In these
      five patients, pain evaluated by visual analog scale was significantly reduced.
      In three patients, bosentan was discontinued because of severe liver dysfunction.
      These results suggest that bosentan is an effective treatment for refractory
      digital ulcers associated with SSc; however, liver function should be carefully
      monitored. Compared to the doses of bosentan used to treat pulmonary
      hypertension, relatively lower doses may effectively control painful digital
      ulcer/gangrene in patients with SSc.

PMID- 21955008
TI  - The use of dabigatran immediately after atrial fibrillation ablation.
AB  - INTRODUCTION: Atrial fibrillation (AF) ablation requires postprocedural
      anticoagulation to prevent thromboembolic events because of the ablation
      procedure itself or due to recurrent AF postprocedure. Dabigatran is a new
      anticoagulant and may be useful after AF ablation to prevent thromboembolic
      events. METHODS AND RESULTS: We evaluated 123 consecutive patients who were
      started on dabigatran after AF ablation. Patients were given enoxaparin 0.5 mg/kg
      at the end of the procedure, which was repeated 12 hours later and then
      discontinued. Dabigatran was started 22 hours postablation with drug dose based
      on renal function. Primary outcomes were thromboembolic events, bleeding
      complications, and side effects over a 30-day follow-up period. The preablation
      anticoagulant was warfarin in 56 (45.5%) patients, dabigatran in 34 (27.6%), and
      aspirin in 26 (21.1%). Seven (5.7%) patients were on no anticoagulant before
      ablation. The patients on dabigatran before ablation with normal renal function
      had the drug stopped 36 hours preablation. There were no preprocedural or
      intraprocedural thromboembolic episodes or bleeding. Three patients received
      dabigatran 75 mg bid and the rest 150 mg bid. There were no postablation strokes,
      transient ischemic attacks, or systemic thromboemboli in any patient. Three
      patients discontinued dabigatran and were changed to warfarin, 2 because of
      gastrointestinal side effects and 1 because of a diffuse rash. CONCLUSIONS:
      Dabigatran is safe and well tolerated after AF ablation. It did not cause
      bleeding complications and there were no thromboembolic events. Dabigatran
      appears to be an alternative to warfarin after AF ablation.

PMID- 21955009
TI  - Voriconazole-induced QT interval prolongation and torsades de pointes.

PMID- 21955010
TI  - Effectiveness of imiquimod 5% cream for treatment of perianal warts in a 28-month
      old child.

PMID- 21955011
TI  - Pediatric acute lymphoblastic leukemia mimicking Henoch-Schonlein purpura.

PMID- 21955012
TI  - Successful treatment of very large congenital infantile fibrosarcoma.

PMID- 21955013
TI  - Successful treatment of pediatric immune thrombocytopenic purpura associated with
      ulcerative colitis.

PMID- 21955014
TI  - Computed tomography findings of the liver in a neonate with Herpes simplex virus
      associated hemophagocytic lymphohistiocytosis.

PMID- 21955015
TI  - Neonatal subcapsular hepatic hematomas presenting as a scrotal wall hematoma.

PMID- 21955016
TI  - Tipepidine hibenzate intoxication.

PMID- 21955017
TI  - Valproic acid intoxication with suicide attempt in a pediatric patient.

PMID- 21955018
TI  - Diencephalic syndrome due to astrocytoma in three infants with failure to thrive.

PMID- 21955019
TI  - Surfactant protein A in gastric fluid at birth as a useful marker of
      differentiation diagnosis between respiratory distress syndrome and transient
      tachypnea of the newborn.

PMID- 21955020
TI  - Late presentation of congenital right diaphragmatic hernia: clinical and
      radiological features.

PMID- 21955021
TI  - Primary bile acid therapy during pregnancy in patients with 3beta-hydroxy-Delta5 
      C27 -steroid oxidoreductase deficiency.

PMID- 21955022
TI  - Explaining the harmonic sequence paradox.
AB  - According to the harmonic sequence paradox, an expected utility decision maker's
      willingness to pay for a gamble whose expected payoffs evolve according to the
      harmonic series is finite if and only if his marginal utility of additional
      income becomes zero for rather low payoff levels. Since the assumption of zero
      marginal utility is implausible for finite payoff levels, expected utility theory
      - as well as its standard generalizations such as cumulative prospect theory -
      are apparently unable to explain a finite willingness to pay. This paper presents
      first an experimental study of the harmonic sequence paradox. Additionally, it
      demonstrates that the theoretical argument of the harmonic sequence paradox only
      applies to time-patient decision makers, whereas the paradox is easily avoided if
      time-impatience is introduced.

PMID- 21955023
TI  - Quantitative analysis of venation patterns of Arabidopsis leaves by supervised
      image analysis.
AB  - The study of transgenic Arabidopsis lines with altered vascular patterns has
      revealed key players in the venation process, but details of the vascularization
      process are still unclear, partly because most lines have only been assessed
      qualitatively. Therefore, quantitative analyses are required to identify subtle
      perturbations in the pattern and to test dynamic modeling hypotheses using
      biological measurements. We developed an online framework, designated Leaf Image
      Analysis Interface (LIMANI), in which venation patterns are automatically
      segmented and measured on dark-field images. Image segmentation may be manually
      corrected through use of an interactive interface, allowing supervision and
      rectification steps in the automated image analysis pipeline and ensuring high
      fidelity analysis. This online approach is advantageous for the user in terms of
      installation, software updates, computer load and data storage. The framework was
      used to study vascular differentiation during leaf development and to analyze the
      venation pattern in transgenic lines with contrasting cellular and leaf size
      traits. The results show the evolution of vascular traits during leaf
      development, suggest a self-organizing mechanism for leaf venation patterning,
      and reveal a tight balance between the number of end-points and branching points
      within the leaf vascular network that does not depend on the leaf developmental
      stage and cellular content, but on the leaf position on the rosette. These
      findings indicate that development of LIMANI improves understanding of the
      interaction between vascular patterning and leaf growth.

PMID- 21955025
TI  - Development of a method to consistently quantify the structural distance between
      scaffolds and to assess scaffold hopping potential.
AB  - We introduce a method to determine a structural distance between any pair of
      molecular scaffolds. The development of this approach was motivated by the need
      to accurately evaluate scaffold hopping studies in virtual screening and
      medicinal chemistry and assess the degree of difficulty involved in facilitating
      a transition from one structure to another. In order to consistently derive
      structural distances, scaffolds of different composition and topology are
      subjected to molecular editing procedures that abstract from original scaffolds
      in a defined manner until compositional and topological equivalence can be
      established. Pairs of corresponding scaffold representations are transformed into
      one-dimensional atom sequences that are aligned using approaches adapted from
      biological sequence comparison. From best scoring atom sequence alignments,
      interscaffold distances are derived. The algorithm is evaluated at different
      levels including the analysis of a series of model scaffolds with defined
      chemical changes, a scaffold library, and scaffolds from reference compounds and
      hits of successful virtual screening applications. It is demonstrated that
      chemically intuitive scaffold distances are obtained for pairs of scaffolds with
      varying composition and topology. Distance threshold values for close and remote
      structural relationships between scaffolds are also determined. The methodology
      is made publicly available in order to provide a basis for a consistent
      assessment of scaffold hopping ability and to aid in the evaluation and
      comparison of virtual screening methods.

PMID- 21955024
TI  - Receptor subtype-dependent galanin actions on gamma-aminobutyric acidergic
      neurotransmission and ethanol responses in the central amygdala.
AB  - The neuropeptide galanin and its three receptor subtypes (GalR1-3) are expressed
      in the central amygdala (CeA), a brain region involved in stress- and anxiety
      related behaviors, as well as alcohol dependence. Galanin also has been suggested
      to play a role in alcohol intake and alcohol dependence. We examined the effects
      of galanin in CeA slices from wild-type and knockout (KO) mice deficient of GalR2
      and both GalR1 and GalR2 receptors. Galanin had dual effects on gamma
      aminobutyric acid (GABA)-ergic transmission, decreasing the amplitudes of
      pharmacologically isolated GABAergic inhibitory postsynaptic potentials (IPSPs)
      in over half of CeA neurons but augmenting IPSPs in the others. The increase in
      IPSP size was absent after superfusion of the GalR3 antagonist SNAP 37889,
      whereas the IPSP depression was absent in CeA neurons of GalR1 * GalR2 double KO
      and GalR2 KO mice. Paired-pulse facilitation studies showed weak or infrequent
      effects of galanin on GABA release. Thus, galanin may act postsynaptically
      through GalR3 to augment GABAergic transmission in some CeA neurons, whereas
      GalR2 receptors likely are involved in the depression of IPSPs. Co-superfusion of
      ethanol, which augments IPSPs presynaptically, together with galanin caused
      summated effects of ethanol and galanin in those CeA neurons showing galanin
      augmented IPSPs, suggesting the two agents act via different mechanisms in this
      population. However, in neurons showing IPSP-diminishing galanin effects, galanin
      blunted the ethanol effects, suggesting a preemptive effect of galanin. These
      findings may increase understanding of the complex cellular mechanisms that
      underlie the anxiety-related behavioral effects of galanin and ethanol in CeA.

PMID- 21955026
TI  - Implantable cardioverter defibrillator implantation without using fluoroscopy in
      a pregnant patient.
AB  - Conventional lead implantation requires fluoroscopic guidance. This may be
      problematic in certain patient groups such as pregnant patients. We report a case
      of an implantable cardioverter defibrillator implantation without fluoroscopy in
      a pregnant patient.

PMID- 21955028
TI  - Self-reported non-adherence to immune-suppressant therapy in liver transplant
      recipients: demographic, interpersonal, and intrapersonal factors.
AB  - Adherence to immune suppressants and follow-up care regimen is important in
      achieving optimal long-term outcomes after organ transplantation. To identify
      patients most at risk for non-adherence, this cross-sectional, descriptive study
      explores the prevalence and correlates of non-adherence to immune-suppressant
      therapy among liver recipients. Anonymous questionnaires mailed consisted of the
      domains: (i) adherence barriers to immune suppressants, (ii) immune suppressants
      knowledge, (iii) demographics, (iv) social support, (v) medical co-morbidities,
      and (vi) healthcare locus of control and other beliefs. Overall response was 49%
      (281/572). Data analyzed for those transplanted within 10 yr of study reveal 50%
      (119/237) recipients or 9.2/100 person years reporting non-adherence. Non
      adherence was reported highest in the 2-5 yr post-transplant phase (69/123, 56%).
      The highest immune-suppressant non-adherence rates were in recipients who are:
      divorced (26/34, 76%, p=0.0093), have a history of substance or alcohol use
      (42/69, 61%, p=0.0354), have mental health needs (50/84, 60%, p=0.0336), those
      who missed clinic appointments (25/30, 83%, p<0.0001), and did not maintain
      medication logs (71/122, 58%, p=0.0168). Respondents who were non-adherent with
      physician appointments were more than four and a half times as likely (OR 4.7,
      95% CI 1.5-14.7, p=0.008) to be non-adherent with immune suppressants. In
      conclusion, half of our respondents report non-adherence to immune suppressants.
      Factors identified may assist clinicians to gauge patients' non-adherence risk
      and target resources.

PMID- 21955029
TI  - A latent variable approach to study gene-environment interactions in the presence
      of multiple correlated exposures.
AB  - Many existing cohort studies initially designed to investigate disease risk as a
      function of environmental exposures have collected genomic data in recent years
      with the objective of testing for gene-environment interaction (G * E) effects.
      In environmental epidemiology, interest in G * E arises primarily after a
      significant effect of the environmental exposure has been documented. Cohort
      studies often collect rich exposure data; as a result, assessing G * E effects in
      the presence of multiple exposure markers further increases the burden of
      multiple testing, an issue already present in both genetic and environment health
      studies. Latent variable (LV) models have been used in environmental epidemiology
      to reduce dimensionality of the exposure data, gain power by reducing
      multiplicity issues via condensing exposure data, and avoid collinearity problems
      due to presence of multiple correlated exposures. We extend the LV framework to
      characterize gene-environment interaction in presence of multiple correlated
      exposures and genotype categories. Further, similar to what has been done in case
      control G * E studies, we use the assumption of gene-environment (G-E)
      independence to boost the power of tests for interaction. The consequences of
      making this assumption, or the issue of how to explicitly model G-E association
      has not been previously investigated in LV models. We postulate a hierarchy of
      assumptions about the LV model regarding the different forms of G-E dependence
      and show that making such assumptions may influence inferential results on the G,
      E, and G * E parameters. We implement a class of shrinkage estimators to data
      adaptively trade-off between the most restrictive to most flexible form of G-E
      dependence assumption and note that such class of compromise estimators can serve
      as a benchmark of model adequacy in LV models. We demonstrate the methods with an
      example from the Early Life Exposures in Mexico City to Neuro-Toxicants Study of
      lead exposure, iron metabolism genes, and birth weight.

PMID- 21955030
TI  - Management tools for managing vapor intrusion.

PMID- 21955031
TI  - Insights into the historical construction of species-rich Mesoamerican seasonally
      dry tropical forests: the diversification of Bursera (Burseraceae, Sapindales).
AB  - * Mesoamerican arid biomes epitomize neotropical rich and complex biodiversity.
      To document some of the macroevolutionary processes underlying the vast species
      richness of Mesoamerican seasonally dry tropical forests (SDTFs), and to evaluate
      specific predictions about the age, geographical structure and niche conservatism
      of SDTF-centered woody plant lineages, the diversification of Bursera is
      reconstructed. * Using a nearly complete Bursera species-level phylogeny from
      nuclear and plastid genomic markers, we estimate divergence times, test for
      phylogenetic and temporal diversification heterogeneity, test for geographical
      structure, and reconstruct habitat shifts. * Bursera became differentiated in the
      earliest Eocene, but diversified during independent early Miocene consecutive
      radiations that took place in SDTFs. The late Miocene average age of Bursera
      species, the presence of phylogenetic geographical structure, and its strong
      conservatism to SDTFs conform to expectations derived from South American SDTF
      centered lineages. * The diversification of Bursera suggests that Mesoamerican
      SDTF richness derives from high speciation from the Miocene onwards uncoupled
      from habitat shifts, during a period of enhanced aridity resulting mainly from
      global cooling and regional rain shadows.

PMID- 21955032
TI  - Reactivity trends within alkoxy radical reactions responsible for chain
      branching.
AB  - Alkoxy radicals are a key component in both the atmospheric and combustion
      oxidation pathways of traditional and alternative fuels. An accurate description
      of their chemistry as it alters with reaction conditions is essential to
      understanding atmospheric and combustion processes involving hydrocarbons.
      Experimental and theoretical data on alkoxy radicals and their reactions are
      scarce, especially for larger chain systems and high temperatures. The present
      work investigates all unimolecular reactions of the methoxy through heptoxy
      radicals using the CBS-Q, G2, and G4 composite computational methods. After
      analysis of the resulting thermodynamic and kinetic parameters, discussions about
      the relative importance of each reaction group and their effects on chain
      branching in the oxidation reaction pathways of hydrocarbons are presented. These
      results are then compared to similar processes in alkyl and alkylperoxy radicals.
      Where discrepancies are found among these three radical systems, discussions
      about possible causes are presented. Of particular interest is the observation
      that 1,6 H-migration reactions are not the dominant pathway in alkoxy radicals,
      as they are in both alkyl and alkylperoxy radicals, at low temperatures. However,
      these H-migrations are expected to play a larger role in reaction mechanisms than
      previously believed, particularly at atmospherically relevant temperatures. This
      will lead to greater diversity in the intermediate and end product species, which
      will in turn add complexity to other atmospheric processes, such as aerosol
      formation and tropospheric ozone production. The current work significantly
      extends the range of alkoxy radicals that are relevant to models for new fuel
      systems. Based on the results of this study, recommendations regarding the
      selection of model systems for future studies are presented.

PMID- 21955027
TI  - The role of selenium in inflammation and immunity: from molecular mechanisms to
      therapeutic opportunities.
AB  - Dietary selenium (]Se), mainly through its incorporation into selenoproteins,
      plays an important role in inflammation and immunity. Adequate levels of Se are
      important for initiating immunity, but they are also involved in regulating
      excessive immune responses and chronic inflammation. Evidence has emerged
      regarding roles for individual selenoproteins in regulating inflammation and
      immunity, and this has provided important insight into mechanisms by which Se
      influences these processes. Se deficiency has long been recognized to negatively
      impact immune cells during activation, differentiation, and proliferation. This
      is related to increased oxidative stress, but additional functions such as
      protein folding and calcium flux may also be impaired in immune cells under Se
      deficient conditions. Supplementing diets with above-adequate levels of Se can
      also impinge on immune cell function, with some types of inflammation and
      immunity particularly affected and sexually dimorphic effects of Se levels in
      some cases. In this comprehensive article, the roles of Se and individual
      selenoproteins in regulating immune cell signaling and function are discussed.
      Particular emphasis is given to how Se and selenoproteins are linked to redox
      signaling, oxidative burst, calcium flux, and the subsequent effector functions
      of immune cells. Data obtained from cell culture and animal models are reviewed
      and compared with those involving human physiology and pathophysiology, including
      the effects of Se levels on inflammatory or immune-related diseases including
      anti-viral immunity, autoimmunity, sepsis, allergic asthma, and chronic
      inflammatory disorders. Finally, the benefits and potential adverse effects of
      intervention with Se supplementation for various inflammatory or immune disorders
      are discussed.

PMID- 21955033
TI  - The effectiveness of opioid maintenance treatment in prison settings: a
      systematic review.
AB  - AIMS: To review evidence on the effectiveness of opioid maintenance treatment
      (OMT) in prison and post-release. METHODS: Systematic review of experimental and
      observational studies of prisoners receiving OMT regarding treatment retention,
      opioid use, risk behaviours, human immunodeficiency virus (HIV)/hepatitis C virus
      (HCV) incidence, criminality, re-incarceration and mortality. We searched
      electronic research databases, specialist journals and the EMCDDA library for
      relevant studies until January 2011. Review conducted according to Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
      RESULTS: Twenty-one studies were identified: six experimental and 15
      observational. OMT was associated significantly with reduced heroin use,
      injecting and syringe-sharing in prison if doses were adequate. Pre-release OMT
      was associated significantly with increased treatment entry and retention after
      release if arrangements existed to continue treatment. For other outcomes,
      associations with pre-release OMT were weaker. Four of five studies found post
      release reductions in heroin use. Evidence regarding crime and re-incarceration
      was equivocal. There was insufficient evidence concerning HIV/HCV incidence.
      There was limited evidence that pre-release OMT reduces post-release mortality.
      Disruption of OMT continuity, especially due to brief periods of imprisonment,
      was associated with very significant increases in HCV incidence. CONCLUSIONS:
      Benefits of prison OMT are similar to those in community settings. OMT presents
      an opportunity to recruit problem opioid users into treatment, to reduce illicit
      opioid use and risk behaviours in prison and potentially minimize overdose risks
      on release. If liaison with community-based programmes exists, prison OMT
      facilitates continuity of treatment and longer-term benefits can be achieved. For
      prisoners in OMT before imprisonment, prison OMT provides treatment continuity.

PMID- 21955034
TI  - Extreme xanthomatosis in patients with both familial hypercholesterolemia and
      cerebrotendinous xanthomatosis.
AB  - Two unrelated individuals were referred to Lipid Clinics in The Netherlands and
      Chile with extreme xanthomatosis and hypercholesterolemia. Both were diagnosed
      with heterozygous familial hypercholesterolemia (heFH) after molecular genetic
      analysis of the low-density lipoprotein (LDL) receptor gene. Since heFH by itself
      could not account for the massive xanthomas, the presence of an additional
      hereditary lipid or lipoprotein disorder was suspected. Further genetic analysis
      revealed homozygozity for mutations in the sterol 27-hydroxylase gene, confirming
      the diagnosis of cerebrotendinous xanthomatosis (CTX). Markedly, the typical
      neurological manifestations of CTX were absent, suggestive of a protective role
      of LDL-receptor deficiency against the severe neurological consequences of CTX.

PMID- 21955036
TI  - Sympathetic imaging with 123-I-MIBG--a new way to predict recurrences after AF
      ablation.

PMID- 21955035
TI  - Fetal development in women with diabetes: imprinting for a life-time?
AB  - OBJECTIVE: To test the hypothesis that fetal exposure to a hyperglycemic
      intrauterine environment in women with type 1 diabetes is associated with
      asymmetrically distributed excessive fetal growth and imprinting consistent with
      adverse health issues later in life. METHODS: We report findings from a
      feasibility study on 19 young adults, born to mothers with type 1 diabetes. Long
      term follow-up of the offspring in young adulthood included: oral glucose
      tolerance test, body mass index (BMI), dual X-ray absorptiometry, and blood
      pressure (BP). We report z-BMI and z-BP to account for varying gender and age.
      RESULTS: The young adults born to women with diabetes averaged 19.9 years at
      follow-up; 37% were female, and 21% African American. Maternal glycohemoglobin
      A(1) concentration in the 2nd trimester was 9.2% for offspring born with
      asymmetric LGA and 7.5% for those born with symmetric LGA or AGA. There was
      significant correlation between maternal glucose control during pregnancy and
      fasting glucose, z-BMI and z-systolic BP in the young adults. CONCLUSION: The
      hyperglycemic intrauterine environment is associated with short-term morbidity,
      manifested as asymmetric LGA (the "fat" baby). In addition, increasing level of
      maternal hyperglycemia during pregnancy is associated with increased adiposity
      and elevated fasting glucose in the young adult offspring.

PMID- 21955037
TI  - Efficacy of the trial-based thought record, a new cognitive therapy strategy
      designed to change core beliefs, in social phobia.
AB  - WHAT IS KNOWN AND BACKGROUND: Social anxiety disorder (SAD) often follows a
      chronic course and is associated with substantial impairment in functioning.
      Although results from clinical trials clearly establish evidence for efficacy of
      cognitive behavioural therapy in treating this disorder, up to 50% of patients
      with SAD show little or no improvement. Thus, new approaches that have promised
      in improving the efficacy of treatment for SAD are needed. One such approach is
      the trial-based thought record (TBTR), which targets the restructuring of
      patients' core beliefs. OBJECTIVE: To determine whether patients receiving TBTR
      would report fewer symptoms of social anxiety and general psychiatric distress
      following treatment, relative to conventional cognitive therapy (CCT). METHODS: A
      two-arm randomized trial comparing TBTR (n = 17) with a set of CCT techniques (n
      = 19), which included the standard seven-column dysfunctional thought record and
      the positive data log in SAD patients according to DSM-IV. RESULTS: Scores on
      many outcome measures decreased significantly across the course of treatment in
      both groups (P < 0.001), including the Liebowitz Social Anxiety Scale, Fear of
      Negative Evaluation Scale (FNE), Social Avoidance and Distress Scale (SADS), Beck
      Anxiety Inventory, and Clinical Global Impression - Improvement. In addition, a
      one-way ancova, taking baseline values as covariates, showed that TBTR was
      significantly more efficacious than CCT in reducing the scores of FNE (P = 0.01
      at mid-treatment and P = 0.004 at post-treatment), and SADS (P = 0.03 at post
      treatment). WHAT IS NEW AND CONCLUSION: This study provides preliminary evidence
      that TBTR is at least as efficacious as CCT in reducing symptoms of SAD, pointing
      to the need for additional studies of TBTR in SAD and other psychiatric
      disorders.

PMID- 21955038
TI  - Examining docking interactions on ERK2 with modular peptide substrates.
AB  - ERK2 primarily recognizes substrates through two recruitment sites, which lie
      outside the active site cleft of the kinase. These recruitment sites bind modular
      docking sequences called docking sites and are potentially attractive sites for
      the development of non-ATP competitive inhibitors. The D-recruitment site (DRS)
      and the F-recruitment site (FRS) bind D-sites and F-sites, respectively. For
      example, peptides that target the FRS have been proposed to inhibit all ERK2
      activity (Galanis, A., Yang, S. H., and Sharrocks, A. D. (2001) J. Biol. Chem.
      276, 965-973); however, it has not been established whether this inhibition is
      steric or allosteric in origin. To facilitate inhibitor design and to examine
      potential coupling of recruitment sites to other ligand recognition sites within
      ERK2, energetic coupling within ERK2 was investigated using two new modular
      peptide substrates for ERK2. Modeling shows that one peptide (Sub-D) recognizes
      the DRS, while the other peptide (Sub-F) binds the FRS. A steady-state kinetic
      analysis reveals little evidence of thermodynamic linkage between the peptide
      substrate and ATP. Both peptides are phosphorylated through a random-order
      sequential mechanism with a k(cat)/K(m) comparable to Ets-1, a bona fide ERK2
      substrate. Occupancy of the FRS with a peptide containing a modular docking
      sequence has no effect on the intrinsic ability of ERK2 to phosphorylate Sub-D.
      Occupancy of the DRS with a peptide containing a modular docking sequence has a
      slight effect (1.3 +/- 0.1-fold increase in k(cat)) on the intrinsic ability of
      ERK2 to phosphorylate Sub-F. These data suggest that while docking interactions
      at the DRS and the FRS are energetically uncoupled, the DRS can exhibit weak
      communication to the active site. In addition, they suggest that peptides bound
      to the FRS inhibit the phosphorylation of protein substrates through a steric
      mechanism. The modeling and kinetic data suggest that the recruitment of ERK2 to
      cellular locations via its DRS may facilitate the formation of F-site selective
      ERK2 signaling complexes, while recruitment via the FRS will likely inhibit ERK2
      through a steric mechanism of inhibition. Such recruitment may serve as an
      additional level of ERK2 regulation.

PMID- 21955039
TI  - Analysis of adsorption and binding behaviors of silver nanoparticles onto a
      pyridyl-terminated surface using XPS and AFM.
AB  - In this study, we analyzed adsorption and binding behaviors of citrate-capped
      silver nanoparticles (AgNPs) on a pyridyl-terminated surface using X-ray
      photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). Adsorption of
      the AgNPs onto the pyridyl-terminated silicon wafer surface was completed through
      pH-controlled sol immersion. The adsorption occurred predominantly at a pH less
      than the pK(b) value of the pyridyl group and more than the pK(a1) of citric
      acid, indicating that the driving force behind adsorption was electrostatic
      interaction. Adsorption of citrate onto the pyridyl group also occurred at pK(a1)
      < pH < pK(b) without AgNPs. According to XPS in the N1s region, larger
      deprotonation from the pyridinium-formed pyridyl groups was demonstrated
      subsequent to adsorption of the AgNPs. The deprotonation from the pyridinium
      indicates the formation of the neutral pyridyl group as the counterpart of
      hydrogen bonding with the carboxyl group of citrate. The binding state between
      the pyridyl group and citrate surrounding AgNPs is expected to be kept stable
      through hydrogen bonding and van der Waals force derived from the AgNPs approach
      to the pyridyl surface.

PMID- 21955040
TI  - Total synthesis and stereochemical revision of acortatarins A and B.
AB  - A first total synthesis of acortatarins A, B, and an enantiomer of the proposed
      structure of acortatarin B is described by using readily available d-sugars. This
      convergent total synthesis revealed the revision of the absolute configuration of
      acortatarin A and structural revision of acortatarin B. The key steps involved
      are regioselective epoxide opening with deprotonated 2,5-disubstituted pyrrole
      and spiroketalization.

PMID- 21955041
TI  - Iranian cancer patients and their perspectives: a qualitative study.
AB  - The incidence of cancer is continuing to rise in Iran. More people are now
      surviving cancer. They may require different kinds of care and support from those
      traditionally available. The expression of needs and how they are met in
      different cultural contexts can inform local assessment of needs and provide
      insights for initiatives in holistic cancer care. This study explores Iranian
      cancer patients' needs from patients' perspective. A qualitative design that
      consists of interviews, field notes and specified demographic information was
      used. Thirty participants were interviewed during the summer and autumn of 2009.
      The study conducted in a cancer research centre (Omid Hospital) in Mashhad, Iran.
      Interviews were analysed using a content analysis method. The results indicate
      that Iranian cancer patients are more likely to suffer from the impact of cancer
      on their daily life than physical symptoms related to the disease and its
      treatment. Cancer affected several aspects of their daily living, including their
      financial situation, ability to work and family life. Cost of treatment and
      psychosocial distress were the two aspects rated by respondents to be the most
      affected. Iranian cancer patients need holistic care which covers all the
      influences that affect their personal's life.

PMID- 21955042
TI  - Case of bleomycin-induced scleroderma.

PMID- 21955043
TI  - Validation of single nucleotide polymorphisms associated with acute rejection in
      kidney transplant recipients using a large multi-center cohort.
AB  - There have been numerous reports proposing a statistically significant
      association between a genetic variant, usually in the form of a single nucleotide
      polymorphism (SNP), and acute rejection (AR). Unfortunately, there are additional
      publications reporting a lack of association with AR when a different cohort of
      recipients was analyzed for the same SNP. The objective of this report was to
      attempt replication of these published finding in our own kidney allograft
      recipient cohort. We analyzed 23 genetic variants, previously reported to have a
      significant association with AR, using a cohort of 969 clinically well-defined
      kidney transplant recipients. Only one SNP, rs6025 (Leiden mutation), within the
      coagulation factor V gene, showed a significant association with a P-value of
      0.011 in a race-adjusted analysis and a P-value of 0.0003 in multiple variable
      analysis. An additional SNP, rs11706052 in IMPDH2, gave a modest P-value of 0.044
      using multiple variable analysis, which is not significant when multiple testing
      is taken into consideration. Our results suggest that careful validation of
      previously reported associations with AR is necessary, and different strategies
      other than candidate gene studies can help to identify causative genetic variants
      associated with AR.

PMID- 21955044
TI  - Discovery of novel checkpoint kinase 1 inhibitors by virtual screening based on
      multiple crystal structures.
AB  - Incorporating receptor flexibility is considered crucial for improvement of
      docking-based virtual screening. With an abundance of crystallographic structures
      freely available, docking with multiple crystal structures is believed to be a
      practical approach to cope with protein flexibility. Here we describe a
      successful application of the docking of multiple structures to discover novel
      and potent Chk1 inhibitors. Forty-six Chk1 structures were first compared in
      single structure docking by predicting the binding mode and recovering known
      ligands. Combinations of different protein structures were then compared by
      recovery of known ligands and an optimal ensemble of Chk1 structures were
      selected. The chosen structures were used in the virtual screening of over 60 000
      diverse compounds for Chk1 inhibitors. Six novel compounds ranked at the top of
      the hits list were tested experimentally, and two of these compounds inhibited
      Chk1 activity-the best with an IC(50) value of 9.6 MUM. Further study indicated
      that achieving a better enrichment and identifying more diverse compounds was
      more likely using multiple structures than using only a single structure even
      when protein structures were randomly selected. Taking into account
      conformational energy difference did not help to improve enrichment in the top
      ranked list.

PMID- 21955046
TI  - Implantable cardioverter-defibrillator recipient attitudes towards device
      deactivation: how much do patients want to know?
AB  - BACKGROUND: Patients receiving implantable cardioverter-defibrillators (ICDs)
      often have severely impaired left ventricular function and a poor prognosis.
      Having an ICD in situ effectively denies them the possibility of a quick,
      arrhythmic death. It is still unclear if and when the end of life and device
      deactivation should be discussed with patients and how much patients want to know
      prior to ICD implantation. METHODS: Patients with an active ICD for chronic heart
      failure were interviewed regarding their attitude toward the ICD, their
      recollection of the consent procedure, and how they felt the end of life should
      be discussed with ICD patients (n = 54). Patients who had received ICD therapies
      (n = 25) were reviewed as a subgroup with extended questions regarding attitudes
      toward device deactivation. RESULTS: Fifty-four patients were recruited. Most
      patients were not aware that the ICD could be deactivated. The vast majority of
      patients (84%) wanted to be involved in the deactivation decision; 40% felt this
      discussion should be prior to ICD implantation but others felt the discussion
      should only occur if the patient was terminally ill (16%) or in the last few days
      of life (5%). CONCLUSION: Patients with ICDs are routinely counseled about the
      benefits of ICDs, but options for device deactivation are not well understood by
      patients. Most patients would like to be involved in deactivation decisions and
      we feel this should be discussed well in advance.

PMID- 21955045
TI  - Inhibiting the TLR4-MyD88 signalling cascade by genetic or pharmacological
      strategies reduces acute alcohol-induced sedation and motor impairment in mice.
AB  - BACKGROUND AND PURPOSE: Emerging evidence implicates a role for toll-like
      receptor 4 (TLR4) in the CNS effects of alcohol. The aim of the current study was
      to determine whether TLR4-MyD88-dependent signalling is involved in the acute
      behavioural actions of alcohol and if alcohol can activate TLR4-downstream MAPK
      and NF-kappaB pathways. EXPERIMENTAL APPROACH: The TLR4 pathway was evaluated
      using the TLR4 antagonist (+)-naloxone (u-opioid receptor-inactive isomer) and
      mice with null mutations in the TLR4 and MyD88 genes. Sedation and motor
      impairment induced by a single dose of alcohol were assessed by loss of righting
      reflex (LORR) and rotarod tests, separately. The phosphorylation of JNK, ERK and
      p38, and levels of IkappaBalpha were measured to determine the effects of acute
      alcohol exposure on MAPK and NF-kappaB signalling. KEY RESULTS: After a single
      dose of alcohol, both pharmacological inhibition of TLR4 signalling with (+)
      naloxone and genetic deficiency of TLR4 or MyD88 significantly (P < 0.0001)
      reduced the duration of LORR by 45-78% and significantly decreased motor
      impairment recovery time to 62-88% of controls. These behavioural actions were
      not due to changes in the peripheral or central alcohol pharmacokinetics.
      IkappaBalpha levels responded to alcohol by 30 min in mixed hippocampal cell
      samples, from wild-type mice, but not in cells from TLR4- or MyD88-deficient
      mice. CONCLUSIONS AND IMPLICATIONS: These data provide new evidence that TLR4
      MyD88 signalling is involved in the acute behavioural actions of alcohol in mice.

PMID- 21955047
TI  - Activation of steroid-sensitive TRPM3 channels potentiates glutamatergic
      transmission at cerebellar Purkinje neurons from developing rats.
AB  - The functional implications of transient receptor potential melastatin 3 (TRPM3)
      activation, the most recently described member of the melastatin subfamily of
      cation permeable TRP channels, have begun to be elucidated in recent years. The
      discovery of TRPM3 activation by the steroid pregnenolone sulfate (PregS) has
      shed new light on the physiological role of this channel. For example, TRPM3
      activation enhances insulin secretion from beta pancreatic cells, induces
      contraction of vascular smooth muscle, and is also involved in the detection of
      noxious heat. Although TRPM3 expression has been detected in several regions of
      the developing and mature brain, little is known about the roles of TRPM3 in
      brain physiology. In this study, we demonstrate the abundant expression of TRPM3
      steroid-sensitive channels in the developing cerebellar cortex. We also show that
      TRPM3-like channels are expressed at glutamatergic synapses in neonatal Purkinje
      cells. We recently showed that PregS potentiates spontaneous glutamate release
      onto neonatal Purkinje cells during a period of active glutamatergic synapse
      formation; we now show that this effect of PregS is mediated by TRPM3-like
      channels. Mefenamic acid, a recently discovered TRPM3 antagonist, blocked the
      effect of PregS on glutamate release. The PregS effect on glutamate release was
      mimicked by other TRPM3 agonists (nifedipine and epipregnanolone sulfate) but not
      by a TRMP3-inactive steroid (progesterone). Our findings identify TRPM3 channels
      as novel modulators of glutamatergic transmission in the developing brain.

PMID- 21955048
TI  - Dependence induced increases in intragastric alcohol consumption in mice.
AB  - Three experiments used the intragastric alcohol consumption (IGAC) procedure to
      examine the effects of variations in passive ethanol exposure on withdrawal and
      voluntary ethanol intake in two inbred mouse strains, C57BL/6J (B6) and DBA/2J
      (D2). Experimental treatments were selected to induce quantitative differences in
      ethanol dependence and withdrawal severity by: (1) varying the periodicity of
      passive ethanol exposure (three, six or nine infusions/day); (2) varying the dose
      per infusion (low, medium or high); and (3) varying the duration of passive
      exposure (3, 5 or 10 days). All experiments included control groups passively
      exposed to water. B6 mice generally self-infused more ethanol than D2 mice, but
      passive ethanol exposure increased IGAC in both strains, with D2 mice showing
      larger relative increases during the first few days of ethanol access. Bout data
      supported the characterization of B6 mice as sippers and D2 mice as gulpers.
      Three larger infusions per day produced a stronger effect on IGAC than six or
      nine smaller infusions, especially in D2 mice. Increased IGAC was strongly
      predicted by cumulative ethanol dose and intoxication during passive exposure in
      both strains. Withdrawal during the passive exposure phase was also a strong
      predictor of increased IGAC in D2 mice. However, B6 mice showed little
      withdrawal, precluding analysis of its potential role. Overall, these data
      support the hypothesis that dependence-induced increases in IGAC are jointly
      determined by two processes that might vary across genotypes: (1) tolerance to
      aversive postabsorptive ethanol effects and (2) negative reinforcement (i.e.
      alleviation of withdrawal by self-administered ethanol).

PMID- 21955049
TI  - Adjuvant combined paclitaxel and carboplatin chemotherapy for glassy cell
      carcinoma of the uterine cervix: report of three cases with clinicopathological
      analysis.
AB  - Glassy cell carcinoma of the uterine cervix (GCC) is a rare form of cervical
      carcinoma that is characterized by aggressiveness and poor prognosis. We reviewed
      a variety of clinicopathological features, treatment strategies, and outcomes in
      three women with GCC. The three patients were successfully treated by radical
      hysterectomy with pelvic/para-aortic lymphadenectomy. The patients had stage Ib1,
      stage IIa, and stage Ib2 tumors without lymph node metastases. A 44-year-old
      woman with stage Ib1 tumor did not undergo adjuvant chemotherapy or radiation
      therapy. She had recurrent pelvic tumors 12 months after surgery, and died 6
      months after the recurrent disease. The histological findings of her cervix,
      which were different from the other two patients, did not show the marked
      infiltration of eosinophils. The other two patients with stage Ib2 and IIa tumors
      underwent adjuvant chemotherapy with paclitaxel and carboplatin, and had disease
      free survival for 4.5 and 9 years. We think that all patients with GCC of stage
      Ib1 or more should undergo adjuvant chemotherapy of paclitaxel and carboplatin or
      other adjuvant therapies.

PMID- 21955051
TI  - Penalized generalized estimating equations for high-dimensional longitudinal data
      analysis.
AB  - We consider the penalized generalized estimating equations (GEEs) for analyzing
      longitudinal data with high-dimensional covariates, which often arise in
      microarray experiments and large-scale health studies. Existing high-dimensional
      regression procedures often assume independent data and rely on the likelihood
      function. Construction of a feasible joint likelihood function for high
      dimensional longitudinal data is challenging, particularly for correlated
      discrete outcome data. The penalized GEE procedure only requires specifying the
      first two marginal moments and a working correlation structure. We establish the
      asymptotic theory in a high-dimensional framework where the number of covariates
      p(n) increases as the number of clusters n increases, and p(n) can reach the same
      order as n. One important feature of the new procedure is that the consistency of
      model selection holds even if the working correlation structure is misspecified.
      We evaluate the performance of the proposed method using Monte Carlo simulations
      and demonstrate its application using a yeast cell-cycle gene expression data
      set.

PMID- 21955052
TI  - Synthesis of 6H-dibenzo[b,d]pyran-6-ones using the inverse electron demand Diels
      Alder reaction.
AB  - A set of coumarin-fused electron-deficient 1,3-dienes was synthesized, which
      differ in the nature of the electron-withdrawing group (EWG) at the terminus of
      the diene unit and (when EWG = CO(2)Me) the nature and position of substituents.
      These dienes reacted with the enamine derived from cyclopentanone and pyrrolidine
      to afford the corresponding cyclopenteno-fused 6H-dibenzo[b,d]pyran-6-ones, most
      likely via a domino inverse electron demand Diels-Alder
      (IEDDA)/elimination/transfer hydrogenation sequence. The parent diene (EWG =
      CO(2)Me, no substituents) was reacted with a range of electron-rich dienophiles
      (mostly enamines) to afford the corresponding 6H-dibenzo[b,d]pyran-6-ones or
      their nondehydrogenated precursors, which were aromatized upon treatment with a
      suitable oxidant. The enamines could either be synthesized prior to the reaction
      or generated in situ. The syntheses of 30 dibenzopyranones are reported.

PMID- 21955050
TI  - Epidermolysis bullosa acquisita: autoimmunity to anchoring fibril collagen.
AB  - Epidermolysis bullosa acquisita (EBA) is a rare and acquired autoimmune
      subepidermal bullous disease of skin and mucosa. EBA includes various distinct
      clinical manifestations resembling genetic dystrophic epidermolysis bullosa
      (DEB), Bullous pemphigus, Brunsting-Perry pemphigoid, or cicatricial pemphigoid.
      These patients have autoantibodies against type VII collagen (C7), an integral
      component of anchoring fibrils (AFs), which are responsible for attaching the
      dermis to the epidermis. Destruction or perturbation of the normal functioning
      AFs clinically results in skin fragility, blisters, erosions, scars, milia, and
      nail loss, all features reminiscent of genetic dystrophic epidermolysis bullosa.
      These anti-C7 antibodies are "pathogenic" because when injected into a mouse, the
      mouse develops an EBA-like blistering disease. Currently, treatment is often
      unsatisfactory; however, some success has been achieved with colchicine, dapsone,
      photopheresis, plasmapheresis, infliximab, rituximab, and IVIG.

PMID- 21955053
TI  - The influence of participation on health-related quality of life in stroke
      patients.
AB  - PURPOSE: Limitations in participation may have independent influences on health
      related quality of life (HRQOL) at early and late phases of stroke recovery.
      METHODS: Consecutive stroke patients were interviewed at months 3 and 12 after
      stroke for modified Barthel Index (MBI), geriatric depression scale (GDS) and WHO
      QOL questionnaire (abbreviated Hong Kong version). London handicap scale (LHS)
      was used to measure limitations in participation. The influence of the six LHS
      domains on the four HRQOL domains, adjusted for MBI and GDS was analysed by
      structural equation modelling with a two-component analysis. RESULTS: Complete
      data were collected in 500 and 433 subjects at months 3 and 12, respectively. On
      multivariate analysis, after adjustment for MBI and GDS, the independence and
      social integration domains of LHS had significant influence on physical and
      social HRQOL, respectively, at both 3 and 12 months post-stroke. The occupation
      domain was a significant factor of physical and environmental HRQOL at month 12,
      but not at month 3. Economic sufficiency had more influence on HRQOL at month 3
      than at month 12. The mobility and orientation domains had no significant
      negative influence on HRQOL. CONCLUSIONS: In stroke patients, participation had
      significant independent influences on HRQOL.

PMID- 21955054
TI  - A comparison of the Screening Activity Limitation and Safety Awareness (SALSA)
      scale to objective hand function assessments.
AB  - PURPOSE: The purpose of this study was to demonstrate construct validity of the
      Screening of Activity Limitation and Safety Awareness (SALSA) scale by comparing
      the measurement outcomes to objective hand function assessments. The SALSA
      questionnaire was developed to measure self-reported activity limitation in
      persons affected by peripheral neuropathy. METHOD: In 25 persons affected by
      leprosy impairment scores were determined via sensory and manual motor testing of
      the hands. The SALSA was administered as well as the Functional Dexterity Test
      (FDT), the Nine Hole Peg Test (NHPT) and daily living tasks from the Smith Hand
      Function Evaluation (SHFE). RESULTS: The SALSA score varied from 16 to 64 (mean
      29.16, SD 12.43). Twelve persons had no activity limitation while the others had
      increasing levels of activity limitation. Performance on the hand function tests
      was slower than established norms for these tests. The SALSA score correlated
      significantly with the NHPT (r = 0.77), the SHFE (r = 0.66) and the fdt (r =
      0.54). Impairment scores correlated with both SALSA and functional tests results.
      CONCLUSION: The credibility of the SALSA scale was enhanced by this validation
      study and showed that the SALSA is a useful assessment tool to measure level of
      function and activity limitation.

PMID- 21955055
TI  - Addressing existential disruption in traumatic spinal cord injury: a new approach
      to human temporality in inpatient rehabilitation.
AB  - This article uses Heidegger's notion of humanp temporality to illuminate the
      meaning of the temporal disruption that can occur after traumatic spinal cord
      injury (TSCI). Though time is seen as important in rehabilitation practice,
      especially in occupational theory, it is often conceptualised in linear terms
      thus missing its existential structure. Our goal in this article is to enhance
      researchers' and rehabilitation clinicians' ways of doing and thinking about
      rehabilitation by revealing and articulating the role of human temporality in
      recovery and re-habilitation in the case of TSCI. Data come from ethnographic
      observations and field notes from one rehabilitation facility, interviews with
      former and current patients of spinal units and interviews with allied health
      staff who work with adults with TSCI. We discuss research and practice
      implications of this work for allied health staff in identifying ways of bringing
      this new approach to temporality into practice.

PMID- 21955056
TI  - Availability, characteristics, and barriers of rehabilitation programs in organ
      transplant populations across Canada.
AB  - Rehabilitation is receiving increasingly more attention from the medical
      community in the management of individuals' pre- and post-organ transplantation.
      A cross-sectional descriptive survey was administered to all known transplant
      programs across Canada to explore the availability, characteristics, and barriers
      of rehabilitation programs pre- and post-heart, lung, kidney, and liver
      transplantation. Of the 58 programs surveyed, 35 agreed to participate (nine
      heart, six lung, 13 kidney, seven liver), and six refused for a response rate of
      71%. Twelve transplant programs that offered rehabilitation were identified (six
      heart, five lung, one liver). All rehabilitation programs identified included
      aerobic exercises, strength training, and education and involved a
      multidisciplinary team. The Six Minute Walk Test and the Medical Outcomes Short
      Form-36 questionnaire were the most commonly used outcome measures. In kidney and
      liver transplant programs, over 50% of respondents from these programs cited lack
      of funding, shortage of health care personnel, and a low volume of patients in a
      centralized region as barriers to providing rehabilitation programs.
      Rehabilitation can play an integral role in pre- and post-transplantation
      management, and barriers to access and provision of rehabilitation for organ
      transplant populations should be examined further.

PMID- 21955057
TI  - New partnerships in health and social care for an era of public spending cuts.
AB  - This article discusses a research partnership framework based on a collaborative
      relationship that was initially established between a carers' organisation and a
      university with the aim of maximising the efficacy and cost-effectiveness of
      health and social care research in an era of public spending cuts. As each
      partner gradually formed several similar partnerships, it was developed into a
      framework for research partnerships between third sector organisations and
      academic institutions. The framework is contextualised within the concepts of
      collaboration and partnership working more generally and then within the
      development of third sector and university partnerships specifically. This is
      followed by a description and discussion of the framework together with a
      critical reflection on how it operated in practice. The ways in which it enhances
      research conducted by third sector organisations and universities and facilitates
      the best use of more limited research funds are also explored. Suggestions are
      then made as to how it can be used and adapted to generate new thinking about
      other similar partnerships at both a national and international level during the
      next few years of considerably reduced public sector expenditure.

PMID- 21955058
TI  - Collectively induced quantum-confined Stark effect in monolayers of molecules
      consisting of polar repeating units.
AB  - The electronic structure of terpyrimidinethiols is investigated by means of
      density-functional theory calculations for isolated molecules and monolayers. In
      the transition from molecule to self-assembled monolayer (SAM), we observe that
      the band gap is substantially reduced, frontier states increasingly localize on
      opposite sides of the SAM, and this polarization in several instances is in the
      direction opposite to the polarization of the overall charge density. This
      behavior can be analyzed by analogy to inorganic semiconductor quantum-wells,
      which, as the SAMs studied here, can be regarded as semiperiodic systems. There,
      similar observations are made under the influence of a, typically external,
      electric field and are known as the quantum-confined Stark effect. Without any
      external perturbation, in oligopyrimidine SAMs one encounters an energy gradient
      that is generated by the dipole moments of the pyrimidine repeat units. It is
      particularly strong, reaching values of about 1.6 eV/nm, which corresponds to a
      substantial electric field of 1.6 * 10(7) V/cm. Close-lying sigma- and pi-states
      turn out to be a particular complication for a reliable description of the
      present systems, as their order is influenced not only by the docking groups and
      bonding to the metal, but also by the chosen computational approach. In the
      latter context we demonstrate that deliberately picking a hybrid functional
      allows avoiding pitfalls due to the infamous self-interaction error. Our results
      show that when aiming to build a monolayer with a specific electronic structure
      one can not only resort to the traditional technique of modifying the molecular
      structure of the constituents, but also try to exploit collective electronic
      effects.

PMID- 21955059
TI  - Left atrial deformation imaging with ultrasound based two-dimensional speckle
      tracking predicts the rate of recurrence of paroxysmal and persistent atrial
      fibrillation after successful ablation procedures.
AB  - OBJECTIVE: Since predictors of recurrence of atrial fibrillation (AF) after
      ablation procedures are poorly defined, this prospective study was conducted to
      assess the value of left atrial (LA) deformation imaging with two-dimensional
      speckle-tracking (2D-ST) to predict AF recurrences after successful ablation
      procedures. METHODS AND RESULTS: One hundred and three consecutive patients (age
      58.1 +/- 16.6 years, 72.8% male) with AF (76 paroxysmal, 27 persistent) and 30
      matched controls underwent transthoracic echocardiography and 2D-ST-LA
      deformation analysis with assessment of LA-radial and LA-longitudinal strain (Sr,
      Sl), and velocities derived from the apical 4- and 2-chamber views (4CV, 2CV). AF
      recurrence was assessed during 6 months of follow-up. For determination of AF
      related LA changes, AF patients were compared to controls and patients with AF
      recurrences after ablation procedures (n = 30, 29.1%) were compared with patients
      who maintained sinus rhythm (n = 73, 70.9%). Atrial deformation capabilities were
      significantly reduced (P < 0.0005) in patients with AF (4CVSl 17.8 +/- 13.5%;
      4CVSr 22.3 +/- 14.9%; 4CV-velocities 2.53 +/- 0.97 seconds) when compared with
      controls (4CVSl 31.3 +/- 12.4%; 4CVSr 30.3 +/- 9.1%; 4CV-velocities 3.48 +/- 1.01
      cm/s). Independent predictors for AF recurrence after ablation procedures were
      2CV-LA-global-strain (Sr, P = 0.03; Sl, P = 0.003), 4CV-LA-gobal-strain (Sr, P =
      0.03; Sl, P = 0.02), and regional LA-septal wall-Sl (P = 0.008). LA-global-strain
      parameters were superior to regional LA function analysis for the prediction of
      AF recurrences, with cutoff values (cov), hazard ratios (HR), positive and
      negative predictive values (PPV, NPV) were: 4CVSl cov, 10.79% (HR 27.8, P <
      0.0005; PPV 78.8%, NPV 93.9%), 4CVSr cov, -16.65% (HR 24.8, P < 0.0005; PPV
      69.4%, NPV 96.6%), 2CVSl cov, 12.31% (HR 22.7, P < 0.0005; PPV 75.8%, NPV 95.3%),
      and 2CVSr cov, -14.9% (HR 12.9, P < 0.0005; PPV 64.3%, NPV 93.2%). CONCLUSION:
      Compared with controls, AF itself seems to decrease LA deformation capabilities.
      The assessment of global LA strain with 2D-ST identifies patients with high risk
      for AF recurrence after ablation procedures. This imaging technique may help to
      improve therapeutic guiding for patients with AF.

PMID- 21955060
TI  - Chemotherapy treatment decision making by professionals and older patients with
      cancer: a narrative review of the literature.
AB  - This narrative review of the literature examines the issues influencing
      chemotherapy treatment of older patients with cancer. Increasing age is
      associated with physical, social and psychological changes, but the rate of
      change differs widely between people, such that chronological age is not a good
      determinant of fitness for treatment. Changes in old age can affect disease
      processes and treatments that are offered. Clinical trials suggest that older
      patients gain benefits from chemotherapy, but with increased toxicity profile.
      Dose reductions may be required, but the effect on outcome is not known. Adjuvant
      chemotherapy is likely to benefit patients with a life expectancy over 5 years,
      although mortality benefits become less pronounced with increasing age. Older
      patients want chemotherapy, as long as side effects do not reduce quality of life
      or ability to function independently. Older patients face barriers to
      communication with professionals, including sensory and memory problems and
      poorer health literacy. Patients should be assessed covering functional,
      physiological and socio-economic domains that identify significant comorbid
      disease and frailty, to ensure that planned chemotherapy is appropriate.
      Successful treatment of older patients with chemotherapy may require
      interventions to support them to ensure all patients who may derive benefit can
      undergo treatment, if they so wish.

PMID- 21955061
TI  - Extra-gynoecial pollen-tube growth in apocarpous angiosperms is phylogenetically
      widespread and probably adaptive.
AB  - * Fusion of floral carpels (syncarpy) in angiosperms is thought to have allowed
      for significant improvements in offspring quantity and quality in syncarpous
      species over gymnosperms and apocarpous (free-carpelled) angiosperms. Given the
      disadvantages of apocarpy, it remains an evolutionary puzzle why many angiosperm
      lineages with free carpels (apocarpy) have been so successful and why some
      lineages show reversals to apocarpy. * To investigate whether some advantages of
      syncarpy may accrue in other ways to apocarpous species, we reviewed previous
      studies of pollen-tube growth in apocarpous species and also documented pollen
      tube growth in nine additional apocarpous species in six families. * Anatomical
      studies of a scattering of apocarpous paleodicots, monocots, and eudicots show
      that, after transiting the style, 'extra' pollen tubes exit fully fertilized
      carpels and grow to other carpels with unfertilized ovules. In many species this
      occurs via openings in the simple carpels, as we report here for Sagittaria
      potamogetifolia, Sagittaria pygmaea, Sedum lineare, and Schisandra sphenanthera.
      * The finding that extra-gynoecial pollen-tube growth is widespread in apocarpous
      species eliminates the possibility of a major fitness cost of apocarpy relative
      to syncarpy and may help to explain the persistence of, and multiple reversals
      to, apocarpy in the evolutionary history of angiosperms.

PMID- 21955062
TI  - Faradaic phase transition of dibenzyl viologen on an HOPG electrode surface
      studied by in situ electrochemical STM and electroreflectance spectroscopy.
AB  - Phase transitions of an adsorption layer of dibenzyl viologen (dBV) as a typical
      diaryl viologen on a basal plane of a highly oriented pyrolytic graphite (HOPG)
      electrode are described using voltammetry, in situ electrochemical scanning
      tunneling microscopy (EC-STM), and electroreflectance (ER) spectroscopy. A
      monolayer redox process at less negative potential than the bulk redox process
      was found to be the first-order faradaic phase transition between a gaslike
      adsorption layer of dication (dBV(2+)) and a 2D condensed monolayer of radical
      cation (dBV(*+)). Comparison of the results of cyclic voltammetry and potential
      step chronoamperometry was made with those of heptyl viologen (HV), which also
      undergoes a faradaic phase transition of the first order. It suggested that the
      contribution of intermolecular pi-pi interaction between benzyl groups of dBV to
      the phase transition is minor and apparently equivalent to interchain interaction
      between the heptyl chains of HV. In situ EC-STM images of the 2D condensed
      monolayer demonstrated stripe patterns of the rows of dBV(*+) molecules forming 3
      fold rotationally symmetric domains. The results of the ER measurements also
      revealed that the orientation of the longitudinal molecular axis of the
      bipyridinium moiety of dBV(*+) molecules lying flat on the HOPG electrode
      surface, most likely with a side-on configuration.

PMID- 21955063
TI  - Key considerations in pharmacotherapy for type 2 diabetes mellitus: a multiple
      target organ approach.
AB  - WHAT IS KNOWN AND OBJECTIVE: Type 2 diabetes mellitus (T2DM) is a progressive
      multisystem disease, and less than half the population with T2DM has achieved the
      recommended glycosylated haemoglobin A1c goal. We aim to present key points to
      consider when selecting pharmacotherapy for the management of T2DM. The selection
      of pharmacotherapy is discussed within the context of the underlying
      pathophysiology of T2DM, currently available treatment options highlighting newer
      agents and current clinical guidelines. COMMENT: Combination therapy regimens
      that target the multiple organ systems involved in the pathophysiology of T2DM
      can be developed based on the mechanism of action (MOA) of each class of agents.
      We compare the pathophysiology of T2DM with the MOA of the currently available
      non-insulin therapeutic options. WHAT IS NEW AND CONCLUSION: Combination therapy
      that efficiently and effectively targets multiorgan correction with the least
      risk for serious adverse events, such as hypoglycaemia and drug interactions, is
      needed when initial treatment fails to achieve the desired clinical outcomes.
      Newer agents, now incorporated in treatment guidelines, increase the range of
      options available to the clinician.

PMID- 21955064
TI  - A new method for aromatic difluoromethylation: copper-catalyzed cross-coupling
      and decarboxylation sequence from aryl iodides.
AB  - A new methodology for aromatic difluoromethylation is described. Aryl iodides
      reacted with alpha-silyldifluoroacetates upon treatment with copper catalyst in
      DMSO or DME to give the corresponding aryldifluoroacetates in moderate to good
      yields. The subsequent hydrolysis of aryldifluoroacetates and KF-promoted
      decarboxylation afforded a variety of difluoromethyl aromatics.

PMID- 21955065
TI  - Migration intentions and illicit substance use among youth in central Mexico.
AB  - This study explored intentions to emigrate and substance use among youth (ages 14
      24) from a central Mexico state with high emigration rates. Questionnaires were
      completed in 2007 by 702 students attending a probability sample of alternative
      secondary schools serving remote or poor communities. Linear and logistic
      regression analyses indicated that stronger intentions to emigrate predicted
      greater access to drugs, drug offers, and use of illicit drugs (marijuana,
      cocaine, inhalants), but not alcohol or cigarettes. Results are related to the
      healthy migrant theory and its applicability to youth with limited educational
      opportunities. The study's limitations are noted.

PMID- 21955066
TI  - Negotiating ecstasy risk, reward, and control: a qualitative analysis of drug
      management patterns among ecstasy-using urban young adults.
AB  - This paper is based on qualitative in-depth interviews conducted from 2008 to
      2009 with 118 ethnically diverse Ecstasy users from the greater Hartford area,
      CT, USA. Participants were urban, primarily Black and Hispanic, aged 18 to 36,
      and had limited higher education compared with samples in previous Ecstasy
      research. Interviews focused on personal background, history of Ecstasy and other
      drug use, and recent sexual events. In this paper, we examine: participants'
      negotiation of perceived risks and benefits of Ecstasy use, behavioral strategies
      employed to minimize risks, and the relationship of risk-benefit analysis,
      motivation for use, frequency of use, and polydrug use to participants' sense of
      control over their Ecstasy use. We conclude with recommendations for intervention
      approaches and suggestions for future research.

PMID- 21955068
TI  - Excellent survival after liver transplantation for isolated polycystic liver
      disease: an European Liver Transplant Registry study.
AB  - Patients with end-stage isolated polycystic liver disease (PCLD) suffer from
      incapacitating symptoms because of very large liver volumes. Liver
      transplantation (LT) is the only curative option. This study assesses the
      feasibility of LT in PCLD. We used the European Liver Transplant Registry (ELTR)
      database to extract demographics and outcomes of 58 PCLD patients. We used Kaplan
      Meier survival analysis for survival rates. Severe abdominal pain (75%) was the
      most prominent symptom, while portal hypertension (35%) was the most common
      complication in PCLD. The explantation of the polycystic liver was extremely
      difficult in 38% of patients, because of presence of adhesions from prior therapy
      (17%). Karnofsky score following LT was 90%. The 1- and 5-year graft survival
      rate was 94.3% and 87.5%, while patient survival rate was 94.8% and 92.3%,
      respectively. Survival rates after LT for PCLD are good.

PMID- 21955069
TI  - Ventricular pacing at maximal sensor rate.

PMID- 21955070
TI  - Fast detection of biomolecules in diffusion-limited regime using micromechanical
      pillars.
AB  - We have developed a micromechanical sensor based on vertically oriented
      oscillating beams, in which contrary to what is normally done (for example with
      oscillating cantilevers) the sensitive area is located at the free end of the
      oscillator. In the micropillar geometry used here, analyte adsorption is confined
      only to the tip of the micropillar, thus reducing the volume from which the
      analyte molecules must diffuse to saturate the surface to a sphere of radius more
      than 2 orders of magnitude smaller than the corresponding linear distance valid
      for adsorption on a macroscopic surface. Hence the absorption rate is 3 orders of
      magnitude faster than on a typical 200 * 20 square micrometer cantilever. Pillar
      oscillations are detected by means of an optical lever method, but the geometry
      is suitable for multiplexing with compact integrated detection. We demonstrate
      our technology by investigating the formation of a single-strand DNA self
      assembled monolayer (SAM) consisting of less than 10(6) DNA molecules and by
      measuring their hybridization efficiency. We show that the binding rate is 1000
      times faster than on a "macroscopic" surface. We also show that the hybridization
      of a SAM of maximum density DNA is 40% or 4 times the value reported in the
      literature. These results suggest that the lower values previously reported in
      the literature can be attributed to incomplete saturation of the surface due to
      the slower adsorption rate on the "macroscopic" surfaces used.

PMID- 21955071
TI  - Deficiency of CRTAP in non-lethal recessive osteogenesis imperfecta reduces
      collagen deposition into matrix.
AB  - Deficiency of any component of the ER-resident collagen prolyl 3-hydroxylation
      complex causes recessive osteogenesis imperfecta (OI). The complex modifies the
      alpha1(I)Pro986 residue and contains cartilage-associated protein (CRTAP), prolyl
      3-hydroxylase 1 (P3H1) and cyclophilin B (CyPB). Fibroblasts normally secrete
      about 10% of CRTAP. Most CRTAP mutations cause a null allele and lethal type VII
      OI. We identified a 7-year-old Egyptian boy with non-lethal type VII OI and
      investigated the effects of his null CRTAP mutation on collagen biochemistry, the
      prolyl 3-hydroxylation complex, and collagen in extracellular matrix. The proband
      is homozygous for an insertion/deletion in CRTAP (c.118_133del16insTACCC). His
      dermal fibroblasts synthesize fully overmodified type I collagen, and 3
      hydroxylate only 5% of alpha1(I)Pro986. CRTAP transcripts are 10% of control.
      CRTAP protein is absent from proband cells, with residual P3H1 and normal CyPB
      levels. Dermal collagen fibril diameters are significantly increased. By
      immunofluorescence of long-term cultures, we identified a severe deficiency (10
      15% of control) of collagen deposited in extracellular matrix, with
      disorganization of the minimal fibrillar network. Quantitative pulse-chase
      experiments corroborate deficiency of matrix deposition, rather than increased
      matrix turnover. We conclude that defects of extracellular matrix, as well as
      intracellular defects in collagen modification, contribute to the pathology of
      type VII OI.

PMID- 21955073
TI  - The hope and hype of multimodality imaging contrast agents.

PMID- 21955072
TI  - Characterizing maternal glycemic control: a more informative approach using
      semiparametric regression.
AB  - OBJECTIVE: To characterize glucose concentrations measured throughout pregnancy
      in women with type 1 diabetes using semiparametric regression analysis to examine
      the gestational time-specific association with fetal outcome. METHODS: We
      conducted a secondary analysis of data from an interdisciplinary program of
      diabetes in pregnancy of women with type 1 diabetes. Semiparametric regression
      was used to characterize glucose concentrations measured using reflectance meters
      throughout pregnancy by examining the time-specific association of maternal
      glucose with delivery of a large for gestational age (LGA) baby. RESULTS: The
      optimal model demonstrated that time-specific differences in glycemic profiles of
      mothers who had LGA versus AGA babies changed at various rates across gestation
      (p = 0.0007). AGA glucose profiles exceeded LGA profiles in the first trimester
      and mid pregnancy; conversely LGA glucose profiles exceeded AGA profiles
      initially during the third trimester. Differences were based on examination of
      95% simultaneous confidence bands. CONCLUSIONS: Semiparametric regression
      techniques enabled synchronous inclusion of all glucose concentrations using
      multi-step modeling. We identified specific periods of gestation where maternal
      glucose concentrations differ for the LGA and AGA developing fetus, with greatest
      distinctions appearing in first and third trimesters. Novel statistical
      approaches that examine time-specific behavior garner insight into longitudinal
      assessment of maternal glycemic control.

PMID- 21955076
TI  - Trevor Keel from the World Gold Council. Interview by Cara Sutton.

PMID- 21955077
TI  - Dendrimer pharmacokinetics: the effect of size, structure and surface
      characteristics on ADME properties.
AB  - Dendrimers show increasing promise as drug-delivery vectors and can be generated
      with a wide range of scaffold structures, sizes and surface functionalities. To
      this point, the majority of studies of dendrimer-based drug-delivery systems have
      detailed pharmacodynamic outcomes, or have followed the pharmacokinetics of a
      solubilized or conjugated drug. By contrast, detailed commentary on the in vivo
      fate of the dendrimer carrier is less evident, even though the pharmacokinetics
      of the carrier will likely dictate both pharmacodynamic and toxicokinetic
      outcomes. In the current article, the influence of size, structure and surface
      functionality on the absorption, distribution, metabolism and elimination (ADME)
      properties of dendrimers have been examined and the implications of these
      findings for delivery system design are discussed.

PMID- 21955078
TI  - Liposomal nanomedicine for breast cancer therapy.
AB  - Liposomes are well-established nanocarriers for improving the therapeutic index
      of anticancer agents. A remarkable understanding in the pathophysiology of breast
      cancer progression has emerged with information on the involved specific
      biomolecules, which may serve as molecular targets for its therapy. Hormonal and
      nonhormonal receptors can both be exploited for targeting to breast cancer cells.
      Targeted delivery of cytotoxic drugs using liposomes is a novel approach for
      breast cancer therapy. In the present article, we summarize molecular targets
      present on the breast cancer cells. Recent developments in liposome-based
      delivery of bioactives for selective treatments of breast cancer are discussed.
      In addition, utilization of bioenvironmental conditions of tumor for liposome
      based targeted delivery is also summed up.

PMID- 21955079
TI  - Quantum dots and carbon nanotubes in oncology: a review on emerging theranostic
      applications in nanomedicine.
AB  - Cancer is one of the main causes of death in the world, and according to the WHO
      it is projected to continue rising. Current diagnostic modalities for the
      detection of cancer include the use of x-rays, magnetic resonance imaging and
      positron emission tomography, among others. The treatment of cancer often
      involves the use (or combination) of chemotherapeutic drugs, radiotherapy and
      interventional surgery (for solid and operable tumors). The application of
      nanotechnology in biology and medicine is advancing rapidly. Recent evidence
      suggests that quantum dots (QDs) can be used to image cancer cells as they
      display superior fluorescent properties compared with conventional chromophores
      and contrast agents. In addition, carbon nanotubes (CNTs) have emerged as viable
      candidates for novel chemotherapeutic drug delivery-platforms. The unique
      photothermal properties of CNTs also allow them to be used in conjunction with
      near infrared radiation and lasers to thermally ablate cancer cells. Furthermore,
      mounting evidence indicates that it is possible to conjugate QDs to CNTs, making
      it possible to exploit their novel attributes in the realm of cancer theranostics
      (diagnostics and therapy). Here we review the current literature pertaining to
      the applications of QDs and CNTs in oncology, and also discuss the relevance and
      implications of nanomedicine in a clinical setting.

PMID- 21955082
TI  - TLR4-MyD88 signalling: a molecular target for alcohol actions.
AB  - Several studies implicate Toll-like receptors (TLRs) in alcohol-induced
      neuroinflammatory processes. The work reported by Wu et al., in this issue of the
      British Journal of Pharmacology, indicates that TLR4 along with its intracellular
      adaptor protein, MyD88, may play crucial roles in the acute actions of alcohol.
      The deletions of TLR4 or MyD88 gene or pharmacological inhibition of TLR4 by (+)
      naloxone were able to attenuate alcohol-induced sedation, motor impairment and
      acute alcohol-induced increases in IkBalpha protein levels in the hippocampus of
      mice. These results clearly suggest that TLR4-MyD88 signalling may play a causal
      role in the mediation of the behavioural effects of acute alcohol.

PMID- 21955083
TI  - Chemical synthesis of N-linked glycans carrying both mannose-6-phosphate and
      GlcNAc-mannose-6-phosphate motifs.
AB  - Mannose-6-phosphate (M6P) containing N-linked glycans are the essential targeting
      signals for hydrolases sorting in eukaryotic cells. To facilitate their
      structural and binding analyses, a highly efficient and convergent method has
      been developed to prepare complex N-linked glycans with well-defined M6P and N
      acetylglucosamine (GlcNAc)-M6P motifs, a newly identified binding element for M6P
      receptors. The GlcNAc-M6P motif was stereoselectively installed at the late stage
      of the synthesis. Sequential deprotection of benzyl and acetate groups provided
      the fully deprotected N-glycans in excellent yield.

PMID- 21955080
TI  - Emerging technologies in medical applications of minimum volume vitrification.
AB  - Cell/tissue biopreservation has broad public health and socio-economic impact
      affecting millions of lives. Cryopreservation technologies provide an efficient
      way to preserve cells and tissues targeting the clinic for applications including
      reproductive medicine and organ transplantation. Among these technologies,
      vitrification has displayed significant improvement in post-thaw cell viability
      and function by eliminating harmful effects of ice crystal formation compared to
      the traditional slow freezing methods. However, high cryoprotectant agent
      concentrations are required, which induces toxicity and osmotic stress to cells
      and tissues. It has been shown that vitrification using small sample volumes
      (i.e., <1 ul) significantly increases cooling rates and hence reduces the
      required cryoprotectant agent levels. Recently, emerging nano- and micro-scale
      technologies have shown potential to manipulate picoliter to nanoliter sample
      sizes. Therefore, the synergistic integration of nanoscale technologies with
      cryogenics has the potential to improve biopreservation methods.

PMID- 21955084
TI  - Bayesian meta-experimental design: evaluating cardiovascular risk in new
      antidiabetic therapies to treat type 2 diabetes.
AB  - Recent guidance from the Food and Drug Administration for the evaluation of new
      therapies in the treatment of type 2 diabetes (T2DM) calls for a program-wide
      meta-analysis of cardiovascular (CV) outcomes. In this context, we develop a new
      Bayesian meta-analysis approach using survival regression models to assess
      whether the size of a clinical development program is adequate to evaluate a
      particular safety endpoint. We propose a Bayesian sample size determination
      methodology for meta-analysis clinical trial design with a focus on controlling
      the type I error and power. We also propose the partial borrowing power prior to
      incorporate the historical survival meta data into the statistical design.
      Various properties of the proposed methodology are examined and an efficient
      Markov chain Monte Carlo sampling algorithm is developed to sample from the
      posterior distributions. In addition, we develop a simulation-based algorithm for
      computing various quantities, such as the power and the type I error in the
      Bayesian meta-analysis trial design. The proposed methodology is applied to the
      design of a phase 2/3 development program including a noninferiority clinical
      trial for CV risk assessment in T2DM studies.

PMID- 21955085
TI  - Immunomodulatory properties of vitamins, flavonoids and plant oils and their
      potential as vaccine adjuvants and delivery systems.
AB  - INTRODUCTION: During the past century, vaccinologists have attempted to mimic
      pathogens in their immune-enhancing capacity. This led to the development of life
      saving vaccines based on live attenuated viruses, bacteria and toxoids. Hence,
      intense research in vaccine adjuvant discovery has focused on toll like
      receptors, mutant toxins and viral and bacterial vectors. Nutritive components
      such as vitamins and select polyphenols also possess immunomodulating properties
      without the potential toxic and adverse side effects of agents that mimic danger
      signals. AREAS COVERED: This review pertains to immunomodulatory properties of
      nutritive components, that is vitamins A, C, D, E, flavonoids and plant oils, as
      potential vaccine adjuvants and delivery systems, covering Pubmed publication
      searches from 1980 through 2011. EXPERT OPINION: This relatively unexplored field
      of the potential of nutritive components as vaccine adjuvants holds great promise
      to promote the development of effective and above all safe vaccines. Hence the
      future focus should be placed on enhancing their efficacy, mainly through novel
      approaches in designing structural derivatives, formulations, delivery systems
      and routes of administration. As safety has been the major issue in development
      of novel vaccines, this new approach will probably result in new discoveries in
      designing safe and effective vaccines.

PMID- 21955086
TI  - Pandemic (H1N1) 2009 in pregnant Japanese women in Hokkaido.
AB  - AIM: No maternal mortality from pandemic (H1N1) 2009 occurred in Japan. However,
      the reasons for this lack of maternal deaths remain unknown. This study was
      performed to investigate how many pregnant women were infected, how many women
      took antiviral drugs for prophylaxis or treatment, and the rate of vaccination
      effectiveness. MATERIAL AND METHODS: A questionnaire study was given to 20500
      postpartum women before leaving obstetric facilities between December 2009 and
      May 2010 in Hokkaido, asking about antiviral drugs, vaccination, and infection
      with pandemic (H1N1) 2009. RESULTS: Approximately one-third (n=7535) of women
      given the questionnaires responded. Of these, 268 women (3.5%) indicated that
      they had contracted influenza. 353 (4.7%) women took antiviral drugs for
      prophylaxis after close contact with an infected person and 140 (39.7%) of 353
      women finally contracted influenza during or after prophylaxis with antiviral
      drugs, accounting for 52.2% (140/268) of all patients. 229 (85.4%) of 268
      patients took antiviral drug for treatment and 6 (2.2%) needed hospitalization,
      but not mechanical ventilation or intensive care unit. 196 of 268 (73.1%)
      patients were already infected before the availability of a vaccine. Among 7328
      candidates for vaccination, 4921 (67.2%) were vaccinated. Infection occurred in
      0.22% (11/4921) and 2.1% (50/2407) of vaccinated and non-vaccinated women,
      respectively. CONCLUSION: Frequent use of antiviral drugs for prophylaxis and
      treatment may partially explain the low infection rate and no maternal mortality
      from pandemic (H1N1) 2009 in Japan. Vaccination reduced infection by 89% in
      pregnant Japanese women.

PMID- 21955087
TI  - A comparison of Frost expression among species and life stages of Drosophila.
AB  - Frost (Fst) is a gene associated with cold exposure in Drosophila melanogaster.
      We used real-time PCR to assess whether cold exposure induces expression of Fst
      in 10 different life stages of D. melanogaster, and adults of seven other
      Drosophila species. We exposed groups of individuals to 0  degrees C (2 h),
      followed by 1 h recovery (22  degrees C). Frost was significantly upregulated in
      response to cold in eggs, third instar larvae, and 2- and 5-day-old male and
      female adults in D. melanogaster. Life stages in which cold did not upregulate
      Fst had high constitutive expression. Frost is located on the opposite strand of
      an intron of Diuretic hormone (DH), but cold exposure did not upregulate DH.
      Frost orthologues were identified in six other species within the Melanogaster
      group (Drosophila sechellia, Drosophila simulans, Drosophila yakuba, Drosophila
      erecta, Drosophila ananassae and Drosophila mauritiana). Frost orthologues were
      upregulated in response to cold exposure in both sexes in adults of all of these
      species. The predicted structure of a putative Frost consensus protein shows
      highly conserved tandem repeats of motifs involved in cell signalling (PEST and
      TRAF2), suggesting that Fst might encode an adaptor protein involved in acute
      stress or apoptosis signalling in vivo.

PMID- 21955088
TI  - Computational screening for active compounds targeting protein sequences:
      methodology and experimental validation.
AB  - The three-dimensional (3D) structures of most protein targets have not been
      determined so far, with many of them not even having a known ligand, a truly
      general method to predict ligand-protein interactions in the absence of three
      dimensional information would be of great potential value in drug discovery.
      Using the support vector machine (SVM) approach, we constructed a model for
      predicting ligand-protein interaction based only on the primary sequence of
      proteins and the structural features of small molecules. The model, trained by
      using 15,000 ligand-protein interactions between 626 proteins and over 10,000
      active compounds, was successfully used in discovering nine novel active
      compounds for four pharmacologically important targets (i.e., GPR40, SIRT1, p38,
      and GSK-3beta). To our knowledge, this is the first example of a successful
      sequence-based virtual screening campaign, demonstrating that our approach has
      the potential to discover, with a single model, active ligands for any protein.

PMID- 21955089
TI  - Sex-specific fitness variation in gynodioecious Beta vulgaris ssp. maritima: do
      empirical observations fit theoretical predictions?
AB  - In gynodioecious species, in which hermaphroditic and female plants co-occur, the
      maintenance of sexual polymorphism relies on the genetic determination of sex and
      on the relative fitness of the different phenotypes. Flower production,
      components of male fitness (pollen quantity and pollen quality) and female
      fitness (fruit and seed set) were measured in gynodioecious Beta vulgaris spp.
      maritima, in which sex is determined by interactions between cytoplasmic male
      sterility (CMS) genes and nuclear restorers of male fertility. The results
      suggested that (i) female had a marginal advantage over hermaphrodites in terms
      of flower production only, (ii) restored CMS hermaphrodites (carrying both CMS
      genes and nuclear restorers) suffered a slight decrease in fruit production
      compared to non-CMS hermaphrodites and (iii) restored CMS hermaphrodites were
      poor pollen producers compared to non-CMS hermaphrodites, probably as a
      consequence of complex determination of restoration. These observations
      potentially have important consequences for the conditions of maintenance of
      sexual polymorphism in B. vulgaris and are discussed in the light of existing
      theory on evolutionary dynamics of gynodioecy.

PMID- 21955090
TI  - Electroanatomic remodeling of the left atrium in paroxysmal and persistent atrial
      fibrillation patients without structural heart disease.
AB  - INTRODUCTION: The nature of the atrial substrate thought to contribute toward
      maintaining atrial fibrillation (AF) outside the pulmonary veins remains poorly
      defined. Therefore, our objective was to determine whether patients with
      paroxysmal and persistent AF have an abnormal electroanatomic substrate within
      the left atrium (LA). METHODS AND RESULTS: Thirty-one patients with AF (17
      paroxysmal AF and 14 persistent AF) were compared with 15 age-matched controls
      with left-sided supraventricular tachycardia (SVT). High-density 3-dimensional
      electroanatomic maps were created and the LA was divided into 8 segments for
      regional analysis. Bipolar voltage, conduction, and effective refractory periods
      (ERPs) of the posterior LA, left atrial appendage (LAA), and distal coronary
      sinus (CSd) and percentage complex signals were assessed. In the majority of LA
      regions, compared with controls, AF patients had: (1) lower mean voltage and a
      higher percentage low voltage; (2) slower conduction; and (3) more prevalent
      complex signals. Many of these changes were more marked in the persistent than
      the paroxysmal AF group. CONCLUSIONS: Patients with AF have lower regional
      voltage, increased proportion of low voltage, slowed conduction, and increased
      proportion of complex signals compared to controls. Many of these changes are
      more pronounced in persistent AF patients, suggesting there may be a progressive
      nature to the changes. Differences occurred in the absence of structural heart
      disease. These substrate abnormalities provide further insight into the
      progressive nature of atrial remodeling and the mechanisms involved in
      maintenance of AF.

PMID- 21955092
TI  - Microbial growth curves: what the models tell us and what they cannot.
AB  - Most of the models of microbial growth in food are Empirical algebraic, of which
      the Gompertz model is the most notable, Rate equations, mostly variants of the
      Verhulst's logistic model, or Population Dynamics models, which can be
      deterministic and continuous or stochastic and discrete. The models of the first
      two kinds only address net growth and hence cannot account for cell mortality
      that can occur at any phase of the growth. Almost invariably, several alternative
      models of all three types can describe the same set of experimental growth data.
      This lack of uniqueness is by itself a reason to question any mechanistic
      interpretation of growth parameters obtained by curve fitting alone. As argued,
      all the variants of the Verhulst's model, including the Baranyi-Roberts model,
      are empirical phenomenological models in a rate equation form. None provides any
      mechanistic insight or has inherent advantage over the others. In principle,
      models of all three kinds can predict non-isothermal growth patterns from
      isothermal data. Thus a modeler should choose the simplest and most convenient
      model for this purpose. There is no reason to assume that the dependence of the
      "maximum specific growth rate" on temperature, pH, water activity, or other
      factors follows the original or modified versions of the Arrhenius model, as the
      success of Ratkowsky's square root model testifies. Most sigmoid isothermal
      growth curves require three adjustable parameters for their mathematical
      description and growth curves showing a peak at least four. Although frequently
      observed, there is no theoretical reason that these growth parameters should
      always rise and fall in unison in response to changes in external conditions.
      Thus quantifying the effect of an environmental factor on microbial growth
      require that all the growth parameters are addressed, not just the "maximum
      specific growth rate." Different methods to determine the "lag time" often yield
      different values, demonstrating that it is a poorly defined growth parameter. The
      combined effect of several factors, such as temperature and pH or aw, need not be
      "multiplicative" and therefore ought to be revealed experimentally. This might
      not be always feasible, but keeping the notion in mind will eliminate theoretical
      assumptions that are hard to confirm. Modern mathematical software allows to
      model growing or dying microbial populations where cell division and mortality
      occur simultaneously and can be used to explain how different growth patterns
      emerge. But at least in the near future, practical problems, like translating a
      varying temperature into a corresponding microbial growth curve, will be solved
      with empirical rate models, which despite not being "mechanistic" are perfectly
      suitable for this purpose.

PMID- 21955091
TI  - Minor components in food oils: a critical review of their roles on lipid
      oxidation chemistry in bulk oils and emulsions.
AB  - Food oils are primarily composed of triacylglycerols (TAG), but they may also
      contain a variety of other minor constituents that influence their physical and
      chemical properties, including diacylglycerols (DAG), monoacylglycerols (MAG),
      free fatty acids (FFA), phospholipids (PLs), water, and minerals. This article
      reviews recent research on the impact of these minor components on lipid
      oxidation in bulk oils and oil-in-water emulsions. In particular, it highlights
      the origin of these minor components, the influence of oil refining on the type
      and concentration of minor components present, and potential physicochemical
      mechanisms by which these minor components impact lipid oxidation in bulk oils
      and emulsions. This knowledge is crucial for designing food, pharmaceutical,
      personal care, and other products with improved stability to lipid oxidation.

PMID- 21955093
TI  - Rosemary and cancer prevention: preclinical perspectives.
AB  - Colorectal cancer is the second leading cause of cancer death in Australia.
      Nutrition, particularly intake of vegetables and certain plant components, has
      been reported to have a major role in cancer risk reduction. Recently, there has
      been a growing research interest in rosemary, a common household plant grown in
      many parts of the world. This study aims to review scientific evidence from all
      studies, published from 1996 to March 2010 that examined the protective effects
      of rosemary on colorectal cancer and other types of cancer. Literature evidence
      from animal and cell culture studies demonstrates the anticancer potential of
      rosemary extract, carnosol, carnosic acid, ursolic acid, and rosmarinic acid. No
      evidence for other rosemary constituents was found. The reported anticancer
      properties were found to arise through the molecular changes in the multiple
      stage process of cancer development, which are dose related and not tissue or
      species specific. This is evidenced by the ability of rosemary to suppress the
      development of tumors in several organs including the colon, breast, liver,
      stomach, as well as melanoma and leukemia cells. The results suggested that the
      different molecular targets modulated by rosemary and its active constituents are
      useful indicators of success in clinical cancer chemo-prevention trials.

PMID- 21955094
TI  - A review on acidifying treatments for vegetable canned food.
AB  - As is well known, pasteurization treatments are not sufficient for destroying
      heat resistance of spore forming microorganisms, which are prevented from
      germination and growing by pH reducing. So, the acidification process becomes one
      of the most important pre-treatments for the canning industry. It is commonly
      applied before pasteurization treatment with the purpose of inhibiting spore
      germination and for reducing heat resistance of the microorganism, thereby
      allowing to reduce the time or temperature values of the heat treatment. With the
      aim to reduce the pH of vegetables several techniques are available but their
      application is not easy to plan. Often, industries define operative conditions
      only on the basis of empirical experience, thus increasing the risk of microbial
      growth or imparting an unpleasant sour taste. With the aim of highlighting the
      correct plan and management of acidification treatments to reach safety without
      degrading quality of canned fruit and vegetables, the topics that are reviewed
      and discussed are the effects of low pH on heat resistance of the most important
      microorganisms, acidification techniques and significant process variables, the
      effect of low pH on sensorial properties, and future trends.

PMID- 21955095
TI  - Glycemic impact and health: new horizons in white bread formulations.
AB  - The challenge of provision of a much wider range of foods of relatively low
      glycemic response than is currently available, especially in terms of cereal
      products, has been highlighted in recent years and this has particular relevance
      to bread consumption. Although there has been some transition to brown bread
      consumption, white bread remains a firm feature in the typical average western
      diet. This review first outlines the relationship between the glycemic impact of
      foods and health. What is important is that relatively small differences in
      glycemic potency of regularly consumed starch foods have been shown to have
      beneficial effects on health outcomes. Second, factors affecting glycemic
      response with particular application to white bread formulations are discussed.
      Novel ways of reformulating this highly favored carbohydrate staple, by using
      composite flours, with the aim of developing products of reduced glycemic
      response are highlighted in this review. Importantly, a new and significant focus
      on the role of unavailable carbohydrate in glycemic improvement is emerging. This
      has important application in increasing accessibility to health benefits by
      contributing to the prevention of and management of glucose intolerance, insulin
      resistance, and associated chronic disease to a wider range of consumers.

PMID- 21955096
TI  - Nonrandom spatial structuring of orchids in a hybrid zone of three Orchis
      species.
AB  - * Nonrandom species-species associations may arise from a range of factors,
      including localized dispersal, intra- and interspecific interactions and
      heterogeneous environmental conditions. Because seed germination and
      establishment in orchids are critically dependent upon the availability of
      suitable mycorrhizal fungi, species-species associations in orchids may reflect
      associations with mycorrhizal fungi. * To test this hypothesis, we examined
      spatial association patterns, mycorrhizal associations and germination success in
      a hybrid zone containing three species of the genus Orchis (Orchis anthropophora,
      Orchis militaris and Orchis purpurea). * Hybridization occurred predominantly
      between O. purpurea and O. militaris. The spatial distribution patterns of most
      pure species and hybrids were independent from each other, except that of O.
      purpurea and its hybrids. The fungal community composition of established
      individuals differed significantly between pure species, but not between hybrids
      and O. purpurea. Seed germination experiments using pure seeds showed that the
      highest number of protocorms were found in regions where adult individuals were
      most abundant. In the case of hybrid seeds, germination was restricted to areas
      where the mother plant was most abundant. * Overall, these results suggest that
      the observed nonrandom spatial distribution of both pure and hybrid plants is
      dependent on the contingencies of the spatial distribution of suitable
      mycorrhizal fungi.

PMID- 21955097
TI  - Electrocatalysis of 2,5-dimercapto-1,3,5-thiadiazole by 3,4-ethylenedioxy
      substituted conducting polymers.
AB  - The electronic properties of electropolymerized films of the 3,4-ethylenedioxy
      substituted conducting polymers (CP) poly(3,4-ethylenedioxythiophene) (PEDOT),
      poly(3,4-ethylenedioxypyrrole) (PEDOP) and poly(3,4-ethylenedioxyselenophene)
      (PEDOS) have been investigated, along with their electrocatalytic activity toward
      2,5-dimercapto-1,3,4-thiadiazole (DMcT). For the electropolymerized films, the
      conductivity onset potential was most negative for PEDOP (-1.50 V), followed by
      PEDOS (-1.35 V) and with PEDOT possessing the most positive onset (-1.15 V). The
      heterogeneous charge transfer rate constant for DMcT in solution at polymer-film
      modified glassy carbon electrodes (GCEs) was studied. It was found that compared
      to PEDOP, both PEDOS and PEDOT performed better as electrocatalysts, with PEDOS
      having a heterogeneous charge transfer rate constant of 1.8 * 10(-3) cm/s. The
      film morphology of the electropolymerized films was investigated via SEM, and
      some film characteristics could be correlated with electrocatalytic activity. The
      potential use of CP/DMcT composites for lithium ion batteries (LIBs) is
      discussed.

PMID- 21955099
TI  - The use of neuroimaging for assessing disorders of pituitary development.
AB  - Magnetic resonance imaging (MRI) is the radiological examination method of choice
      for evaluating hypothalamo-pituitary-related endocrine disease and is considered
      essential in the assessment of patients with suspected hypothalamo-pituitary
      pathology. Physicians involved in the care of such patients have, in MRI, a
      valuable tool that can aid them in determining the pathogenesis of their
      patients' underlying pituitary conditions. Indeed, the use of MRI has led to an
      enormous increase in our knowledge of pituitary morphology, improving, in
      particular, the differential diagnosis of hypopituitarism. Specifically, MRI
      allows detailed and precise anatomical study of the pituitary gland by
      differentiating between the anterior and posterior pituitary lobes. MRI
      recognition of pituitary hyperintensity in the posterior part of the sella, now
      considered a marker of neurohypophyseal functional integrity, has been the most
      striking finding in the diagnosis and understanding of certain forms of
      'idiopathic' and permanent growth hormone deficiency (GHD). Published data show a
      number of correlations between pituitary abnormalities as observed on MRI and a
      patient's endocrine profile. Indeed, several trends have emerged and have been
      confirmed: (i) a normal MRI or anterior pituitary hypoplasia generally indicates
      isolated growth hormone deficiency that is mostly transient and resolves upon
      adult height achievement; (ii) patients with multiple pituitary hormone
      deficiencies (MPHD) seldom show a normal pituitary gland; and (iii) the classic
      triad of ectopic posterior pituitary, pituitary stalk hypoplasia/agenesis and
      anterior pituitary hypoplasia is more frequently reported in MPHD patients and is
      generally associated with permanent GHD. Pituitary abnormalities have also been
      reported in patients with hypopituitarism carrying mutations in several genes
      encoding transcription factors. Establishing endocrine and MRI phenotypes is
      extremely useful for the selection and management of patients with
      hypopituitarism, both in terms of possible genetic counselling and in the early
      diagnosis of evolving anterior pituitary hormone deficiencies. Going forward,
      neuroimaging techniques are expected to progressively expand and improve our
      knowledge and understanding of pituitary diseases.

PMID- 21955100
TI  - An Interview with Matthew P. Greving, PhD. Interview by Vicki Glaser.
AB  - Matthew P. Greving is Chief Scientific Officer at Nextval Inc., a company founded
      in early 2010 that has developed a discovery platform called MassInsightTM.. He
      received his PhD in Biochemistry from Arizona State University, and prior to that
      he spent nearly 7 years working as a software engineer. This experience in
      solving complex computational problems fueled his interest in developing
      technologies and algorithms related to acquisition and analysis of high
      dimensional biochemical data. To address the existing problems associated with
      label-based microarray readouts, he beganwork on a technique for label-free mass
      spectrometry (MS) microarray readout compatible with both matrix-assisted
      laser/desorption ionization (MALDI) and matrix-free nanostructure initiator mass
      spectrometry (NIMS). This is the core of Nextval's MassInsight technology, which
      utilizes picoliter noncontact deposition of high-density arrays on mass-readout
      substrates along with computational algorithms for high-dimensional data
      processingand reduction.

PMID- 21955098
TI  - Efficacy and safety of ustekinumab in Japanese patients with moderate-to-severe
      plaque-type psoriasis: long-term results from a phase 2/3 clinical trial.
AB  - This phase 2/3, double-blind, placebo-controlled study was designed to assess the
      safety and efficacy of ustekinumab in Japanese patients with moderate-to-severe
      plaque-type psoriasis. Overall, 158 patients were randomized to receive
      ustekinumab 45 or 90 mg at weeks 0, 4, and every 12 weeks, or placebo with cross
      over to ustekinumab at week 12. The primary end-point was the proportion of
      patients achieving at least 75% improvement in Psoriasis Area and Severity Index
      (PASI 75) at week 12. Physician's Global Assessment (PGA), Dermatology Life
      Quality Index (DLQI), Nail Psoriasis Severity Index and joint pain Visual Analog
      Scale (VAS) were also measured. At week 12, 59.4% and 67.7% of ustekinumab 45 and
      90 mg patients achieved PASI 75, respectively, compared with 6.5% in the placebo
      group (P < 0.0001 each). PASI 75 responses were maintained through week 64 in
      65.0% and 78.6% of the ustekinumab-treated patients, respectively. Placebo cross
      over patients had similar responses to ustekinumab-treated patients. Significant
      improvements in PGA, DLQI and VAS scores were observed at week 12 and generally
      maintained over time. Adverse events during the placebo-controlled period were
      similar among groups (45 mg, 65.6%; 90 mg, 59.7%; placebo, 65.6%). Serious
      adverse events were observed in 0%, 4.8% and 6.3% of patients, respectively.
      Through week 72, similar rates and types of adverse events and serious adverse
      events were reported in patients receiving 45 and 90 mg. Rates of injection site
      reactions and antibodies to ustekinumab were low. Ustekinumab was efficacious and
      generally well-tolerated in Japanese patients with moderate-to-severe plaque-type
      psoriasis through 72 weeks. These results are consistent with those reported in
      the global, phase 3 studies.

PMID- 21955102
TI  - Superiority of virtual microscopy versus light microscopy in transplantation
      pathology.
AB  - Virtual microscopy has begun to change conventional pathology practice. We tested
      the reliability of this new technology in transplantation pathology. We studied
      40 kidney transplant biopsies for cause and compared reproducibility of Banff
      scores using virtual slides versus glass slides. Three glass slides per biopsy
      were scanned as high-resolution digital slides using Aperio ScanScope. Three
      pathologists independently reviewed the biopsies: twice by glass slides and twice
      by virtual slides. Eleven histopathological lesions were scored and used to
      construct diagnosis according to Banff criteria. The intra-observer
      reproducibility of Banff scores was substantially good using either virtual
      slides or glass slides (mean kappa: 0.69 vs. 0.64, p>0.05). The inter-observer
      reproducibility of Banff scores was better in virtual slides than in glass slides
      (mean kappa: 0.42 vs. 0.28, p<0.001). Among the lesions, transplant
      glomerulopathy scoring by virtual slides showed the highest inter-observer
      reproducibility, with a similar accuracy to glass slides. The agreement for acute
      rejection between virtual and glass slides was not different from the agreement
      between two readings of glass slides. Thus, virtual microscopy is a reliable and
      more reproducible technology and has several advantages over glass slides, e.g.,
      accessibility via internet, no fading. We recommend virtual microscopy for
      transplant diagnostics, including utilization for clinical trials.

PMID- 21955103
TI  - Pediatric and Adult Congenital Endocardial Lead Extraction or Abandonment
      Decision (PACELEAD) survey of lead management.
AB  - BACKGROUND: Nonfunctional, dysfunctional, recalled, or additional endocardial
      leads in pediatric and congenital heart disease patients pose significant
      challenges for management. There are no set standards for lead extraction in this
      patient population. METHODS: Physician members of the Pediatric and Adult
      Congenital Electrophysiology Society (PACES) were contacted via e-mail and
      invited to respond to a 33-question online Pediatric and Adult Congenital
      Endocardial Lead Extraction or Abandonment (PACELEAD) survey. RESULTS: Responses
      were received from 75 of 138 (54%) physician members of PACES. Institutional
      volumes of device placement (<25 devices/year for 51% of responders), patients
      with abandoned leads (<25 patients for 71%), and lead extractions (<10
      extractions/year for 51% and no extractions for 29%) were low for the majority of
      responders. Personal experience with lead extraction was also minimal with 49%
      not performing the procedure and 39% with less than 40 leads extracted as primary
      operator. Most responders (54, 72%) refer their lead extractions to another
      practitioner or facility with more experience. Responders were more likely to
      recommend lead extraction (>70%) for class IIa indications such as bacteremia,
      chronic pain that is not medically manageable, and functional leads with
      ipsilateral venous occlusion. Lead abandonment was favored (>70%) for one class
      IIb indication, a functional lead that is not currently being used. CONCLUSIONS:
      Optimal lead management is challenging in pediatric and congenital heart disease
      patients, and considerable variability of practice is reported in their care. Low
      institutional and personal volumes may account for this variability.

PMID- 21955104
TI  - Corpus callosum size and shape alterations in adolescent inhalant users.
AB  - Inhalants, frequently abused during adolescence, are neurotoxic to white matter.
      We investigated the impact of inhalant misuse on the morphology of the corpus
      callosum (CC), the largest white matter bundle in the brain, in an adolescent
      sample of inhalant users [n = 14; mean age = 17.3; standard deviation (SD) =
      1.7], cannabis users (n = 11; mean age = 19.7; SD = 1.7) and community controls
      (n = 9; mean age = 19.5; SD = 2.6). We identified significant morphological
      differences in the CC among inhalant users compared with community controls.
      There were no morphological differences between inhalant and cannabis users. Our
      findings may represent the early stages of neurobiological damage associated with
      chronic inhalant misuse.

PMID- 21955105
TI  - Analysis of differentially expressed genes in ovaries of polytocous versus
      monotocous dairy goats using suppressive subtractive hybridization.
AB  - In this study, suppressive subtractive hybridization (SSH) was performed to
      screen differentially expressed genes in ovarian tissues between polytocous and
      monotocous goats. From the SSH cDNA library, we obtained 29 differentially
      expressed sequence tags (ESTs) that have high similarity with known genes in the
      public database, which were involved in signal transduction, transcriptional
      regulation, cellular molecular dynamics, cytoskeleton, metabolism and oxidation
      reduction. In addition, one novel EST that has no similarity with known genes in
      the public database was obtained. Eight ESTs, TIMP1, NUCB1, OAZ1, CXXC5, CAPNS2,
      ATP5A1, Z and RPL5, were further examined for the reproducibility of the SSH data
      by the real-time quantitative PCR. The results confirmed an increased expression
      of respective mRNA in ovarian tissues of polytocous goats compared with those of
      monotocous goats. The study has identified several genes (known or unknown) that
      may have effect on follicular development, ovulation and egg activation in goats.

PMID- 21955107
TI  - Self-assembly of large-scale and ultrathin silver nanoplate films with tunable
      plasmon resonance properties.
AB  - We describe a rapid, simple, room-temperature technique for the production of
      large-scale metallic thin films with tunable plasmonic properties assembled from
      size-selected silver nanoplates (SNPs). We outline the properties of a series of
      ultrathin monolayer metallic films (8-20 nm) self-assembled on glass substrates
      in which the localized surface plasmon resonance can be tuned over a range from
      500 to 800 nm. It is found that the resonance peaks of the films are strongly
      dependent on the size of the nanoplates and the refractive index of the
      surrounding dielectric. It is also shown that the bandwidth and the resonance
      peak of the plasmon resonance spectrum of the metallic films can be engineered by
      simply controlling aggregation of the SNP. A three-dimensional finite element
      method was used to investigate the plasmon resonance properties for individual
      SNPs in different dielectrics and plasmon coupling in SNP aggregates. A 5-17
      times enhancement of scattering from these SNP films has been observed
      experimentally. Our experimental results, together with numerical simulations,
      indicate that this self-assembly method shows great promise in the production of
      nanoscale metallic films with enormous electric-field enhancements at visible and
      near-infrared wavelengths. These may be utilized in biochemical sensing, solar
      photovoltaic, and optical processing applications.

PMID- 21955106
TI  - Inflammatory changes during epileptogenesis and spontaneous seizures in a mouse
      model of mesiotemporal lobe epilepsy.
AB  - PURPOSE: Neuroinflammation appears as a prominent feature of the mesiotemporal
      lobe epilepsy syndrome (MTLE) that is observed in human patients and animal
      models. However, the precise temporal relationship of its development during
      epileptogenesis remains to be determined. The aim of the present study was to
      investigate (1) the time course and spatial distribution of neuronal death
      associated with seizure development, (2) the time course of microglia and
      astrocyte activation, and (3) the kinetics of induction of mRNAs from
      neuroinflammatory-related proteins during the emergence of recurrent seizures.
      METHODS: Experimental MTLE was induced by the unilateral intrahippocampal
      injection of kainate in C57BL/6 adult mice. Microglial and astrocytic changes in
      both ipsilateral and contralateral hippocampi were examined by respectively
      analyzing griffonia simplicifolia (GSA) lectin staining and glial fibrillary
      acidic protein (GFAP) immunoreactivity. Changes in mRNA levels of selected genes
      of cytokine and cytokine regulatory proteins (interleukin-1beta, IL-1beta;
      interleukin-1 receptor antagonist, IL-1Ra; suppressor of cytokine signaling 3,
      SOCS3) and enzymes of the eicosanoid pathway (group IVA cytosolic phospholipase
      A2, cPLA(2)-alpha; cycloxygenase-2, COX-2) were studied by reverse transcription
      quantitative real time polymerase chain reaction. KEY FINDINGS: Our data show an
      immediate cell death occurring in the kainate-injected hippocampus during the
      initial status epilepticus (SE). A rapid increase of activated lectin-positive
      cells and GFAP-immunoreactivity was subsequently detected in the ipsilateral
      hippocampus. In the same structure, Il-1beta, IL-1Ra, and COX-2 mRNA were
      specifically increased during SE and epileptogenesis with a different time
      course. Conversely, the expression of SOCS3 mRNA, a surrogate marker of
      interleukin signaling, was mainly increased in the contralateral hippocampus
      after SE. SIGNIFICANCE: Our data show that specific neuroinflammatory pathways
      are activated in a time- and structure-dependent manner with putative distinct
      roles in epileptogenesis.

PMID- 21955108
TI  - Spontaneous labor curves in women with pregnancies complicated by diabetes.
AB  - OBJECTIVE: To test the hypothesis that the first stage of labor will be longer in
      nulliparous and multiparous women with diabetes compared to non-diabetic
      counterparts. METHODS: A retrospective analysis was performed from 228,668
      deliveries between 2002-2008 from the Consortium of Safe Labor (National
      Institute of Child Health and Human Development, National Institutes of Health).
      Patients with spontaneous onset of labor from 37 0/7-41 6/7 weeks gestation were
      included (71,282) and classified as nulliparous or multiparous. Pregnancies were
      further subdivided regarding presence of preexisting diabetes (preDM) or
      gestational diabetes (GDM) and normal controls. Labor curves were created
      matching for body mass index (BMI) and neonatal birth weight. Statistical
      analysis was performed on descriptive variables using chi(2) with significance
      designated as p < 0.05. RESULTS: Among nulliparous patients, there were 118 women
      with preDM and 475 women with GDM; 25,771 patients served as normal controls.
      Among multiparous women, there were 311 with preDM, 1,079 with GDM and 43,528 in
      the control group. Although differences in dilatation rates were observed in
      nulliparous and multiparous women with and without diabetes, labor progression
      was similar between the subgroups when matched for maternal BMI and birth weight.
      CONCLUSIONS: Labor curves of women with preDM and GDM approximate those of non
      diabetics, regardless of BMI, birth weight, or parity.

PMID- 21955109
TI  - Introduction to special issue: moving forward in pediatric neuropsychology.
AB  - This special issue of The Clinical Neuropsychologist focuses on advances in the
      emerging subspecialty of pediatric neuropsychology. The national and
      international contributions in this issue cover a range of key clinical,
      research, training, and professional issues specific to pediatric
      neuropsychology. The genesis for this project developed out of a series of talks
      at the Philadelphia Pediatric Neuropsychology Symposium in 2010, hosted by the
      Stein Family Fellow, the Department of Psychology of the College of Arts and
      Sciences at Drexel University, and the Philadelphia Neuropsychology Society.
      Articles that explore clinical practice issue focus on the assessment of special
      medical populations with congenital and/or acquired central nervous system
      insults. Research articles investigate the core features of developmental
      conditions, the use of technology in neuropsychological research studies, and
      large sample size genomic, neuropsychological, and imaging studies of under
      represented populations. The final series of articles examine new considerations
      in training, advocacy, and subspecialty board certification that have emerged in
      pediatric neuropsychology. This introductory article provides an overview of the
      articles in this special issue and concluding thoughts about the future of
      pediatric neuropsychology.

PMID- 21955110
TI  - Parent- and self-ratings of executive functions in adolescents and young adults
      with spina bifida.
AB  - This study examined the agreement and consistency of parent- and self-report of
      executive functioning (EF) (Behavior Rating Inventory of Executive Functions;
      BRIEF) in an adolescent cohort of youth with myelomeningocele and shunted
      hydrocephalus (MMH). A total of 30 youth participants with MMH and their parents
      were recruited during adolescence (age 11-18, mean age 14), and a smaller sample
      (n = 13) was re-evaluated during young adulthood (age 18-26, mean age 22). Parent
      and self-report T-scores were moderately correlated during adolescence (General
      Executive Composite, GEC, r = .504, p = .007) and adulthood (GEC, r = .571, p =
      .041). Compared to adolescent self-ratings, parent-ratings suggested higher
      levels of overall executive dysfunction and problems with metacognitive abilities
      during adolescence. Preliminary results from a small follow up sample, however,
      suggest that self- and parent-report of executive functioning may become more
      comparable during young adulthood. These preliminary data also suggest stability
      of deficit and/or possible improvement in executive presentation during the
      transition from adolescence to adulthood in this clinical population.
      Implications of these findings are discussed.

PMID- 21955111
TI  - Changing perspectives on Landau-Kleffner syndrome.
AB  - Landau-Kleffner syndrome (LKS) is a childhood disorder characterized by an
      acquired aphasia that emerges in association with epileptiform
      electroencephalographic abnormalities. The language loss is often characterized
      by a severe disturbance of auditory language comprehension (verbal auditory
      agnosia) combined with a substantial disruption of expressive language. Comorbid
      behavioral disturbances commonly involve hyperactivity and attentional problems
      but sometimes encompass a more pervasive pattern of difficulties resembling an
      autism spectrum disorder. Now one the most frequently described forms of acquired
      aphasia in children, LKS has had a profound influence on both neurological
      practice and cognitive neuroscience. Here, we review current conceptualizations
      of LKS, consider its pleomorphic manifestations and discuss existing and future
      diagnostic issues and dilemmas. The potential relevance of LKS to understanding
      other disorders, including autistic regression, is considered.

PMID- 21955112
TI  - The "where" and "what" in developmental dyscalculia.
AB  - Developmental dyscalculia (DD) is a congenital deficit that affects the ability
      to acquire arithmetical skills. Individuals with DD have problems learning
      standard number facts and procedures. Estimates of the prevalence rate of DD are
      similar to those of developmental dyslexia. Recent reports and discussions
      suggest that those with DD suffer from specific deficits (e.g., subitizing,
      comparative judgment). Accordingly, DD has been described as a domain-specific
      disorder that involves particular brain areas (e.g., intra-parietal sulcus).
      However, we and others have found that DD is characterized by additional
      deficiencies and may be affected by domain-general (e.g., attention) factors.
      Hence "pure DD" might be rather rare and not as pure as one would think. We
      suggest that the heterogeneity of symptoms that commonly characterize learning
      disabilities needs to be taken into account in future research and treatment.

PMID- 21955113
TI  - Pediatric neuropsychology: toward subspecialty designation.
AB  - Clinical neuropsychology is a rapidly expanding field of study in the
      psychological sciences whose practitioners are expert in the assessment,
      treatment, and research of individuals with known or suspected central nervous
      system disease or disorder. Pediatric neuropsychology has emerged as a distinct
      subspecialty area with related education, training, and clinical expertise for a
      growing number of neuropsychologists. This paper details the numerous steps taken
      by two affiliated organizations, the American Board of Clinical Neuropsychology
      and its membership organization, the American Academy of Clinical
      Neuropsychology, in the interest of the larger pediatric neuropsychology
      community and in pediatric neuropsychology subspecialty development.

PMID- 21955116
TI  - Curious results with palladium- and platinum-carrying polymers in mass cytometry
      bioassays and an unexpected application as a dead cell stain.
AB  - We describe the synthesis of metal-chelating polymers (MCPs) with four different
      pendant polyaminocarboxylate ligands (EDTA, DTPA, TTHA, DOTA) and an orthogonal
      end-group, either a fluorescein molecule or a bismaleimide linker for antibody
      attachment. Polymer characterization by a combination of (1)H NMR, UV/vis
      absorption measurements, and thermal gravimetric analysis (TGA) indicated that
      each chain of the fluorescein-terminated polymers contained one dye molecule.
      These polymer samples were loaded with three different types of lanthanide ions
      as well as palladium and platinum ions. The numbers of metal atoms per chain were
      determined by a combination of UV/vis and conventional ICP-MS measurements. The
      experiments with lanthanide ions demonstrated that a net anionic charge on the
      polymer is important for water solubility. These experiments also showed that at
      least one type of lanthanide ion (La(3+)) is capable of forming a bimetallic
      complex with pendant DTPA groups. Conditions were developed for loading these
      polymers with palladium and platinum ions. While these polymers could be
      conjugated to antibodies, the presence of Pd or Pt ions in the polymer interfered
      with the ability of the antibody to recognize its antigen. For example, a goat
      anti-mouse (secondary) antibody labeled with polymers that contain Pd or Pt no
      longer recognized a primary antibody in a sandwich assay. In mass cytometry
      assays, these Pd- or Pt-containing MCPs were very effective in recognizing dead
      cells and provide a new and robust assay for distinguishing live cells from dead
      cells.

PMID- 21955117
TI  - Synthesis and structural verification of the xylomannan antifreeze substance from
      the freeze-tolerant Alaskan beetle Upis ceramboides.
AB  - Tetra-, hexa-, and octasaccharide subunits of the [->4)-beta-D-Manp-(1->4)-beta-D
      Xylp-(1->](n) xylomannan motif proposed as the structure of a novel nonprotein,
      thermal hysteresis-producing antifreeze substance from the freeze-tolerant
      Alaskan beetle Upis ceramboides have been accessed by total chemical synthesis.
      Comparison of their NMR spectral data with data of the isolate lends strong
      support to the proposed structure. Synthetic tetrasaccharides representing
      various linkage isomers considered (alpha- rather than beta-manno, and linkage
      through mannose O3 rather than O4) show more significant chemical shift
      differences with the isolate and are therefore excluded from further
      consideration.

PMID- 21955118
TI  - Logistic Bayesian LASSO for identifying association with rare haplotypes and
      application to age-related macular degeneration.
AB  - Rare variants have been heralded as key to uncovering "missing heritability" in
      complex diseases. These variants can now be genotyped using next-generation
      sequencing technologies; nonetheless, rare haplotypes may also result from
      combination of common single nucleotide polymorphisms available from genome-wide
      association studies (GWAS). The National Eye Institute's data on age-related
      macular degeneration (AMD) is such an example. Studies on AMD had identified
      potential rare variants; however, due to lack of appropriate statistical tools,
      effects of individual rare haplotypes were never studied. Here we develop a
      method for identifying association with rare haplotypes for case-control design.
      A logistic regression based retrospective likelihood is formulated and is
      regularized using logistic Bayesian LASSO (LBL). In particular, we penalize the
      regression coefficients using appropriate priors to weed out unassociated
      haplotypes, making it possible for the rare associated ones to stand out. We
      applied LBL to the AMD data and identified common and rare haplotypes in the
      complement factor H gene, gaining insights into rare variants' contributions to
      AMD beyond the current literature. This analysis also demonstrates the richness
      of GWAS data for mapping rare haplotypes-a potential largely unexplored.
      Additionally, we conducted simulations to investigate the performance of LBL and
      compare it with Hapassoc. Our results show that LBL is much more powerful in
      identifying rare associated haplotypes when the false positive rates for both
      approaches are kept the same.

PMID- 21955119
TI  - Engineering lubrication in articular cartilage.
AB  - Despite continuous progress toward tissue engineering of functional articular
      cartilage, significant challenges still remain. Advances in morphogens, stem
      cells, and scaffolds have resulted in enhancement of the bulk mechanical
      properties of engineered constructs, but little attention has been paid to the
      surface mechanical properties. In the near future, engineered tissues will be
      able to withstand and support the physiological compressive and tensile forces in
      weight-bearing synovial joints such as the knee. However, there is an increasing
      realization that these tissue-engineered cartilage constructs will fail without
      the optimal frictional and wear properties present in native articular cartilage.
      These characteristics are critical to smooth, pain-free joint articulation and a
      long-lasting, durable cartilage surface. To achieve optimal tribological
      properties, engineered cartilage therapies will need to incorporate approaches
      and methods for functional lubrication. Steady progress in cartilage lubrication
      in native tissues has pushed the pendulum and warranted a shift in the articular
      cartilage tissue-engineering paradigm. Engineered tissues should be designed and
      developed to possess both tribological and mechanical properties mirroring
      natural cartilage. In this article, an overview of the biology and engineering of
      articular cartilage structure and cartilage lubrication will be presented.
      Salient progress in lubrication treatments such as tribosupplementation,
      pharmacological, and cell-based therapies will be covered. Finally, frictional
      assays such as the pin-on-disk tribometer will be addressed. Knowledge related to
      the elements of cartilage lubrication has progressed and, thus, an opportune
      moment is provided to leverage these advances at a critical step in the
      development of mechanically and tribologically robust, biomimetic tissue
      engineered cartilage. This article is intended to serve as the first stepping
      stone toward future studies in functional tissue engineering of articular
      cartilage that begins to explore and incorporate methods of lubrication.

PMID- 21955120
TI  - QRS characteristics fail to reliably identify ventricular tachycardias that
      require epicardial ablation in ischemic heart disease.
AB  - OBJECTIVES: We tested proposed algorithms for idiopathic and nonischemic
      tachycardias for their ability to identify epicardial LV-VT origins. BACKGROUND:
      Several ECG features have been reported to identify epicardial origins for left
      ventricular tachycardias (LV-VTs) in the absence of myocardial infarction. Only
      limited data exist in postinfarction patients. METHODS: The QRS features of 24
      VTs that were ablated from the epicardium and 39 left ventricular VTs ablated
      from the endocardium were retrospectively analyzed for various 12-lead ECG
      features previously reported. RESULTS: No ECG feature consistently predicted an
      epicardial LV-VT origin in infarct-related tachycardias, with epicardial VTs
      showing slightly longer QRS durations (189 +/- 32 ms in epicardial vs 179 +/- 37
      ms in endocardial, P = 0.28). Pseudo-delta duration was 38 +/- 27 versus 47 +/-
      27 ms (P = 0.2), intrinsicoid deflection time 93 +/- 35 versus 86 +/- 32 ms (P =
      0.4), shortest RS 97 +/- 38 versus 99 +/- 32 ms (P = 0.77), and median deflection
      index 0.82 +/- 0.25 versus 0.87 +/- 0.22 (P = 0.43). The finding of a Q wave in
      lead I and the absence of a Q wave in the inferior leads failed to predict an
      epicardial origin in superior LV-VT sites. Q waves in any inferior lead and
      aVR/aVL-ratio<1 were not specific for an epicardial origin in inferior sites (all
      P = ns). Furthermore, all inferior LV-VTs showed a Q wave in the inferior leads
      which correlated with pre-existing Q-waves in sinus rhythm (P = 0.045).
      CONCLUSION: Proposed 12-lead ECG features for differentiation of epicardial
      versus endocardial sites for nonischemic LV-VTs do not reliably identify VTs that
      require ablation from the epicardium. Endocardial mapping should be the first
      approach to catheter ablation for VTs in patients with ischemic heart disease.

PMID- 21955122
TI  - Identification of specific sites in the third intracellular loop and carboxyl
      terminus of the Bombyx mori pheromone biosynthesis activating neuropeptide
      receptor crucial for ligand-induced internalization.
AB  - Sex pheromone production in most moths is mediated by the pheromone biosynthesis
      activating neuropeptide receptor (PBANR). Using fluorescent Bombyx mori PBANR
      (BmPBANR) chimeras to study PBANR regulation, we previously showed that BmPBANR
      undergoes rapid ligand-induced internalization, that the endocytotic motif
      resides between residues 358-367 of the BmPBANR C terminus, and that the
      internalization pathway is clathrin-dependent. Here, we sought to expand our
      understanding of the molecular mechanisms underlying BmPBANR function and
      regulation by transiently expressing a series of fluorescent BmPBANR chimeric
      constructs in cultured Spodoptera frugiperda (Sf9) cells and assaying for
      internalization of a fluorescently labelled ligand. Pharmacological inhibition of
      phospholipase C significantly reduced internalization, suggesting that BmPBANR
      regulation proceeds via a conventional G-protein-dependent pathway. This was
      further supported by impaired internalization following site-directed mutagenesis
      of R263 and R264, two basic residues at the transmembrane 6 intracellular
      junction that are thought to stabilize G-protein coupling via electrostatic
      interactions. Ala substitution of S333 and S366, two consensus protein kinase C
      sites in the C terminus, likewise impaired internalization, as did RNA
      interference-mediated knockdown of Sf9 protein kinase C. N-terminal truncations
      of BmPBANR indicate that the first 27 residues are not necessary for cell surface
      trafficking or receptor functionality.

PMID- 21955121
TI  - Data analysis strategy for maximizing high-confidence protein identifications in
      complex proteomes such as human tumor secretomes and human serum.
AB  - Detection of biologically interesting, low-abundance proteins in complex
      proteomes such as serum typically requires extensive fractionation and high
      performance mass spectrometers. Processing of the resulting large data sets
      involves trade-offs between confidence of identification and depth of protein
      coverage; that is, higher stringency filters preferentially reduce the number of
      low-abundance proteins identified. In the current study, an alternative database
      search and results filtering strategies were evaluated using test samples ranging
      from purified proteins to ovarian tumor secretomes and human serum to maximize
      peptide and protein coverage. Full and partial tryptic searches were compared
      because substantial numbers of partial tryptic peptides were observed in all
      samples, and the proportion of partial tryptic peptides was particularly high for
      serum. When data filters that yielded similar false discovery rates (FDR) were
      used, full tryptic searches detected far fewer peptides than partial tryptic
      searches. In contrast to the common practice of using full tryptic specificity
      and a narrow precursor mass tolerance, more proteins and peptides could be
      confidently identified using a partial tryptic database search with a 100 ppm
      precursor mass tolerance followed by filtering of results using 10 ppm mass error
      and full tryptic boundaries.

PMID- 21955123
TI  - Integration and dissociation of limb elements in flying vertebrates: a comparison
      of pterosaurs, birds and bats.
AB  - Flapping flight has evolved independently in three vertebrate clades: pterosaurs,
      birds and bats. Each clade has a unique flight mechanism involving different
      elements of the forelimb. Here, patterns of limb integration are examined using
      partial correlation analysis within species and matrix correlation analysis
      across species to test whether the evolution of flapping flight has involved
      developmental dissociation of the serial homologues in the fore- and hind limb in
      each clade. Our sample included seven species of birds, six species of bats, and
      three species of pterosaurs for which sufficient sample sizes were available. Our
      results showed that, in contrast to results previously reported for quadrupedal
      mammals, none of the three clades demonstrated significant integration between
      serial homologues in the fore- and hind limb. Unexpectedly, there were few
      consistent patterns of within-forelimb correlations across each clade, suggesting
      that wing integration is not strongly constrained by functional relationships.
      However, there was significant integration within the hind limbs of pterosaurs
      and birds, but not bats, possibly reflecting the differing functions of hind
      limbs (e.g. upright support vs. suspension) in these clades.

PMID- 21955125
TI  - Size control in the synthesis of 1-6 nm gold nanoparticles via solvent-controlled
      nucleation.
AB  - We report a facile synthetic route for size-controlled preparation of gold
      nanoparticles. Nearly monodisperse gold nanoparticles with core diameters of 1-6
      nm were obtained by reducing AuP(Phenyl)(3)Cl with tert-butylamine borane in the
      presence of dodecanethiol in the solvent mixture of benzene and CHCl(3).
      Mechanism studies have shown that the size control is achieved by the solvent
      controlled nucleation in which the nuclei concentration increases with increasing
      the fraction of CHCl(3), leading to smaller particles. It was also found that,
      following the solvent-controlled nucleation, particle growth occurs via ligand
      replacement of PPh(3) on the nuclei by Au(I)thiolate generated by the digestive
      etching of small particles. This synthetic strategy was successfully demonstrated
      with other alkanethiols of different chain length with which size-controlled,
      monodisperse gold nanoparticles were prepared in remarkable yield without
      requiring any postsynthesis treatments.

PMID- 21955124
TI  - Evidence of function for conserved noncoding sequences in Arabidopsis thaliana.
AB  - * Whole genome duplication events provide a lineage with a large reservoir of
      genes that can be molded by evolutionary forces into phenotypes that fit
      alternative environments. A well-studied whole genome duplication, the alpha
      event, occurred in an ancestor of the model plant Arabidopsis thaliana. Retained
      segments of the alpha-event have been defined in recent years in the form of
      duplicate protein coding sequences (alpha-pairs) and associated conserved
      noncoding DNA sequences (CNSs). Our aim was to identify any association between
      CNSs and alpha-pair co-functionality at the gene expression level. * Here, we
      tested for correlation between CNS counts and alpha-pair co-expression and
      expression intensity across nine expression datasets: aerial tissue, flowers,
      leaves, roots, rosettes, seedlings, seeds, shoots and whole plants. * We provide
      evidence for a putative regulatory role of the CNSs. The association of CNSs with
      alpha-pair co-expression and expression intensity varied by gene function,
      subgene position and the presence of transcription factor binding motifs. A range
      of possible CNS regulatory mechanisms, including intron-mediated enhancement,
      messenger RNA fold stability and transcriptional regulation, are discussed. *
      This study provides a framework to understand how CNS motifs are involved in the
      maintenance of gene expression after a whole genome duplication event.

PMID- 21955126
TI  - Late-night salivary cortisol for diagnosis of Cushing's syndrome by liquid
      chromatography/tandem mass spectrometry assay.
AB  - BACKGROUND: Late-night salivary cortisol (LNSC) measurements have been
      increasingly used by physicians as an initial diagnostic test for evaluation of
      patients with clinical suspicion of Cushing's syndrome (CS). Published studies
      include various numbers of cases, controls and importantly, various assay methods
      (vast majority various immunoassays), as well as various methods to generate cut
      points. MATERIALS AND METHODS: The retrospective study evaluated the diagnostic
      utility of LNSC measurements in 249 patients evaluated for possibility of CS
      because of various clinical conditions using liquid chromatography/tandem mass
      spectrometry method (LC-MS/MS). CS was confirmed in 47 patients (18.9%) and
      excluded in 202 (81.1%) patients at the time of analysis. RESULTS: Late-night
      salivary cortisol was abnormal or >2.8 nmol/l in 35 of 47 patients with CS;
      sensitivity of 74.5% and elevated in 20 of 202 patients who were found not to
      have CS; specificity 90.1%. Using receiver-operator characteristic statistics for
      calculation of the most optimal sensitivity and specificity, the cut-off based on
      this data was LNSC > 2.1 nmol/l with sensitivity of 83.0% and specificity of
      84.2%. CONCLUSION: Analysis of data at one referral institution showed somewhat
      limited sensitivity of LNSC for diagnosis of CS using current reference ranges.

PMID- 21955127
TI  - Discontinued drugs in 2010: oncology drugs.
AB  - The Pharmaceutical Industry is currently undergoing a period of rapid change as
      the pressures of the financial markets highlight fundamental inefficiencies in
      the current business model. The Achilles heel for the industry is the
      unacceptable level of attrition in clinical drug development. An imperative for
      the industry is to reduce the cost and increase the efficiency of Research and
      Development (R&D). This article provides an analysis of cancer drugs dropped from
      the industry pipeline in 2010 and offers a perspective on how the future oncology
      drug pipeline might evolve.

PMID- 21955128
TI  - Effects of capsaicin on nitric oxide synthase isoforms in prepubertal rat ovary.
AB  - Nitric oxide (NO) has emerged as an important intra-ovarian regulatory factor. We
      investigated effects of low dose capsaicin (CAP) treatment on the different NOS
      isoforms in prepubertal rat ovaries. Fifteen 21-day-old female Sprague-Dawley
      rats were divided randomly into three groups. The first group received no
      treatment, the second group received 0.5 mg/kg/day CAP dissolved in the vehicle,
      and the third group was treated with the vehicle only. The animals were
      euthanized by ether inhalation after 15 days and their ovaries were excised.
      Ovaries were fixed in 10% neutral buffered formalin and embedded in paraffin.
      Sections were processed for standard immunohistochemistry using the labeled
      streptavidin-biotin technique for expression of nNOS, eNOS and iNOS. We
      demonstrated that CAP induced expression of NOS isotypes including eNOS, iNOS and
      nNOS in prepubertal rat ovaries. CAP may lead to release of NO either directly
      from nerves or indirectly by evoking release from other cells via the action of
      neuropeptides that are released from afferent terminals and are involved in
      regulating female reproductive function.

PMID- 21955130
TI  - Evaluation of improved zirconyl hematoxylin compared to the classical pH 2.5
      Alcian blue method for demonstrating acid mucins.
AB  - Acid mucins have diagnostic significance for many pathological conditions,
      especially in certain tumors. We compared the classical pH 2.5 Alcian blue method
      to a new, improved zirconyl hematoxylin (IZH) method for demonstrating acid
      mucins using two fixatives: Bouin's solution and 10% neutral buffered formalin
      (NBF). We used rabbit small intestine, large intestine and trachea. Specimens
      were fixed in Bouin's solution and NBF. A total of 160 paraffin sections were
      prepared and stained with pH 2.5 Alcian blue and IZH. The stained acid mucins
      were assessed using digital image analysis software. Stained mucins were
      quantified for each staining procedure and fixative. No important differences
      were observed in acid mucin staining by either method after either fixative. The
      IZH method provides results as good as pH 2.5 Alcian blue and can be used to
      obtain reliable staining for acid mucins.

PMID- 21955131
TI  - Intact parathyroid hormone levels in renal transplant patients with normal
      transplant function.
AB  - INTRODUCTION: Chronic kidney disease mineral and bone disorder (CKD-MBD) is
      common in patients who have undergone kidney transplantation. There is limited
      information on the extent to which patients with normal renal function after
      transplantation have persistent disturbances in their mineral metabolism. AIM:
      The aim of the study is to investigate the prevalence of elevated intact
      parathyroid hormone (iPTH) levels at least one yr after transplantation in
      patients living with a first renal transplant with normal transplant function.
      METHODS: A retrospective, observational study of 607 patients was collected from
      the Norwegian Renal Registry. Of these, iPTH was recorded for 360 patients.
      RESULTS: One hundred and eighty-eight patients (52%) had elevated iPTH levels.
      Twenty-six patients (7%) had iPTH levels >2.5 times the upper limit of normal
      (ULN). Patients with a pre-emptive transplant were significantly younger than the
      patients who had received treatment with dialysis (p < 0.0001). The prevalence of
      iPTH > ULN was significantly higher in patients with a pre-emptive transplant (p
      = 0.037). CONCLUSIONS: In post-transplant patients with normal transplant
      function, our data indicate that more than 50% have elevated levels of iPTH more
      than one yr after transplantation. If elevated iPTH level is associated with
      mortality in this patient population, it may have major impact on clinical
      treatment guidelines.

PMID- 21955132
TI  - Effects of phosphate on the transport of Escherichia coli O157:H7 in saturated
      quartz sand.
AB  - Consumption of groundwater contaminated with E. coli O157:H7 has led to several
      waterborne disease outbreaks over the past decade. A thorough understanding of
      the transport of E. coli O157:H7 within the soil-groundwater system is critical
      to the protection of public health. Although phosphate is ubiquitous in the
      natural environment, the influence of phosphate on the transport of E. coli
      O157:H7 in the groundwater system remains unknown. In this research, we performed
      column transport experiments to evaluate the effect of phosphate on the transport
      of E. coli O157:H7 cells within saturated sand. The pH of the solutions was
      maintained at 7.2, the ionic strength varied from 10 to 100 mM, and the phosphate
      concentration ranged from 0 to 1 mM. Our results show that (1) phosphate could
      enhance the transport of E. coli O157:H7 cells under both ionic strength
      conditions; (2) E. coli O157:H7 displayed lower retention in sand under higher
      ionic strength conditions; (3) increased phosphate in the mobile aqueous phase
      led to the release of previously immobilized E. coli O157:H7 cells. The response
      of E. coli O157:H7 cells to variations in phosphate concentrations and ionic
      strength conditions are explained using the extended DLVO (XDLVO) theory and the
      steric repulsion caused by extracellular macromolecules. In summary, our results
      suggest that phosphate could widen the spread of E. coli O157:H7 cells, and
      potentially other types of bacterial cells, within the soil-groundwater system.

PMID- 21955133
TI  - Polypropylene mesh as an alternative option for uterine preservation in pelvic
      reconstruction in patients with uterine prolapse.
AB  - AIM:   The aim of this study was to evaluate the efficacy and safety of
      polypropylene mesh for uterine preservation during pelvic reconstruction in
      patients with severe uterine prolapse. MATERIALS AND METHODS: The study included
      67 women with severe uterine prolapse (pelvic organ prolapse quantification stage
      III/IV) who received transvaginal mesh reconstruction with uterine preservation.
      Surgery combined with a transobturator membrane sling procedure (tension-free
      vaginal tape-transobturator route) was performed in 54 patients. Among them, 18
      had urodynamic stress incontinence, 30 had occult stress urinary incontinence,
      and six had mixed urinary incontinence. Objective assessments were carried out
      with the pelvic organ prolapse quantification staging system, urodynamic
      examination, and 1-h pad test. Evaluation of urinary and prolapse symptoms
      comprised the subjective assessment. RESULTS: The mean follow-up interval was
      19.6 months (12-40 months). The objective cure rate for the treatment of uterine
      prolapse was 89.5%, and the objective cure rate for the treatment of urinary
      incontinence was more than 90%. CONCLUSIONS: Uterine preservation in pelvic
      reconstruction is technically feasible and the subjective and objective
      assessments imply that uterine preservation in pelvic reconstruction is an
      alternative option for indicated patients.

PMID- 21955134
TI  - Power keys: a novel class of topological descriptors based on exhaustive subgraph
      enumeration and their application in substructure searching.
AB  - We present a novel class of topological molecular descriptors, which we call
      power keys. Power keys are computed by enumerating all possible linear, branch,
      and cyclic subgraphs up to a given size, encoding the connected atoms and bonds
      into two separate components, and recording the number of occurrences of each
      subgraph. We have applied these new descriptors for the screening stage of
      substructure searching on a relational database of about 1 million compounds
      using a diverse set of reference queries. The new keys can eliminate the vast
      majority (>99.9% on average) of nonmatching molecules within a fraction of a
      second. More importantly, for many of the queries the screening efficiency is
      100%. A common feature was identified for the molecules for which power keys have
      perfect discriminative ability. This feature can be exploited to obviate the need
      for expensive atom-by-atom matching in situations where some ambiguity can be
      tolerated (fuzzy substructure searching). Other advantages over commonly used
      molecular keys are also discussed.

PMID- 21955135
TI  - Persistent cutaneous neonatal herpes caused by Herpes simplex virus-2.

PMID- 21955137
TI  - Liposome-encapsulated hemoglobin alleviates hearing loss after transient cochlear
      ischemia and reperfusion in the gerbil.
AB  - To test liposome-encapsulated hemoglobin (LEH) in transient cochlear
      ischemia/reperfusion as a model of sudden deafness, Mongolian gerbils were
      randomly assigned to receive 2 mL/kg of either low-affinity LEH (l-LEH, P5002 =
      40 mm Hg), high-affinity LEH (h-LEH, P5002 = 10 mm Hg), homologous red blood
      cells (RBCs), or saline (each group n = 6) 30 min before 15-min occlusion of the
      bilateral vertebral arteries and reperfusion. Sequential changes in hearing were
      assessed by auditory brain response 1, 4, and 7 days after ischemia/reperfusion,
      when the animals were sacrificed for pathological studies. h-LEH was
      significantly more protective than l-LEH in suppressing hearing loss, in contrast
      to RBC or saline treatment, at 8, 16, and 32 kHz, where hearing loss was most
      severe (P < 0.05 between any two groups) on the first day after cochlear
      ischemia/reperfusion. Thereafter, hearing loss improved gradually in all groups,
      with a significant difference among groups up to 7 days, when morphological
      studies revealed that the inner hair cells but not the outer hair cells, were
      significantly lost in the groups in the same order. The results suggest that
      pretreatment with h-LEH is significantly more protective than l-LEH in mitigating
      hearing loss and underlying pathological damage, in contrast to transfusion or
      saline infusion 7 days after transient cochlear ischemia/reperfusion.

PMID- 21955136
TI  - Cyclosporin A and cardioprotection: from investigative tool to therapeutic agent.
AB  - Ischaemic heart disease (IHD) is the leading cause of death and disability
      worldwide. The pathophysiological effects of IHD on the heart most often result
      from the detrimental effects of acute ischaemia-reperfusion injury (IRI) on the
      myocardium. Therefore, novel therapeutic targets for protecting the myocardium
      against acute IRI are required to reduce injury to the heart, preserve cardiac
      function and improve clinical outcomes in patients with IHD. In this regard, the
      mitochondrial permeability transition pore (mPTP) has emerged as a critical
      target for cardioprotection which is readily amenable to intervention at the time
      of myocardial reperfusion. The formation and opening of the mPTP at the onset of
      myocardial reperfusion is a major determinant of mitochondrial dysfunction and
      cardiomyocyte death in the setting of acute IRI. The seminal discovery in the
      late 1980s that mPTP opening could be pharmacologically inhibited by the
      immunosuppressive agent, cyclosporin A (CsA), has been fundamental in the
      elucidation of the critical role of the mPTP as a mediator of acute IRI and,
      therefore, a viable target for cardioprotection. Its initial role as an
      investigative tool was used to identify mitochondrial cyclophilin D to be a
      regulatory component of the mPTP. The mPTP as a viable target for
      cardioprotection has recently been translated into the clinical setting with CsA
      reducing myocardial infarct size in patients. In this article, we review the
      intriguing role of CsA as a tool for investigating the mPTP as a target for
      cardioprotection and its potential role as a therapeutic agent for patients with
      IHD.

PMID- 21955138
TI  - Information about the taste stimulates choice of unfamiliar healthful food
      products.
AB  - BACKGROUND: The present study aimed to assess whether taste information about
      unfamiliar low-fat and fruit and vegetable products leads to more positive taste
      expectations and stimulates choice for these products. The impact of level of
      food neophobia on such effects was studied. METHODS: The present study had a two
      (taste information: yes/no) by four (food products: low-fat cheese/very low-fat
      margarine spread/fruit juice/fruit and vegetable juice) between subjects design
      among a convenience sample of 396 university students. Taste information was
      delivered by means of a poster providing information on the taste of the offered
      food product. Primary outcome measurements were taste expectations and product
      choice. Level of food neophobia, appetite level, mood states, usual intake of
      fruit, vegetables and fat, and demographics were taken into account as potential
      confounders. RESULTS: Taste information had no effect on taste expectations,
      although it had a positive effect on choosing unfamiliar healthful products.
      These effects were not moderated by level of food neophobia. CONCLUSIONS:
      Offering taste information on unfamiliar healthful products appears to be a
      promising strategy for increasing the first-time trial of such products,
      independent of the participants' level of food neophobia.

PMID- 21955139
TI  - Nonlinear phenomena in multiferroic nanocapacitors: joule heating and
      electromechanical effects.
AB  - We demonstrate an approach for probing nonlinear electromechanical responses in
      BiFeO(3) thin film nanocapacitors using half-harmonic band excitation
      piezoresponse force microscopy (PFM). Nonlinear PFM images of nanocapacitor
      arrays show clearly visible clusters of capacitors associated with variations of
      local leakage current through the BiFeO(3) film. Strain spectroscopy measurements
      and finite element modeling point to significance of the Joule heating and show
      that the thermal effects caused by the Joule heating can provide nontrivial
      contributions to the nonlinear electromechanical responses in ferroic
      nanostructures. This approach can be further extended to unambiguous mapping of
      electrostatic signal contributions to PFM and related techniques.

PMID- 21955140
TI  - Is maternal diabetes a risk factor for childhood obesity?
AB  - OBJECTIVE: Our objective is to determine if there is a relationship between
      diabetes during pregnancy and childhood obesity, in our inner-city, African
      American population. METHODS: Pertinent child, neonatal and maternal pregnancy
      and delivery data were collected from mothers of children age 2-5 years old.
      Outcome variable definition was based on children's body mass index (BMI)
      subgroups; independent variable definition on birthweight subgroups based on
      customized growth percentiles. Covariates included pre and postnatal factors.
      Those covariates marginally related to diabetes (p < 0.2) by bivariate analyses,
      were allowed to compete in logistic regression, with p < 0.05 significant.
      RESULTS: Four hundred and ninety-three patients were enrolled, of which 35 (7.1%)
      had diabetes during pregnancy. Children of diabetic mothers were more likely to
      be obese at age 2-5 years than those of non-diabetics (p = 0.004). Five of 20
      covariates had p < 0.2 in bivariate setting. Following stepwise logistic
      regression, diabetes and maternal prepregnancy BMI were significant determinants
      of childhood obesity. When large-for-gestational age (LGA) was added into the
      model, diabetes was no longer significant (p = 0.105); only LGA (p = 0.008) and
      maternal prepregnancy BMI (p = 0.032) were significantly associated with
      childhood obesity. CONCLUSIONS: In our inner-city, primarily African-American
      population, diabetes in pregnancy is significantly related to childhood obesity
      at age 2-5 years. Well-controlled diabetes during pregnancy that avoids
      macrosomia may lead to prevention of future childhood obesity as well.

PMID- 21955141
TI  - The Bcl-2/Bcl-XL inhibitor ABT-737 promotes death of retinoblastoma cancer cells.
AB  - PURPOSE: Retinoblastoma is a malignant tumor that usually develops in early
      childhood. During retinoblastoma spreading, RB1 gene inactivation is followed by
      additional genomic modifications which progressively lead to resistance of tumor
      cells to death. Drugs that act at downstream levels of death signaling pathways
      should therefore be interesting in killing retinoblastoma cells. ABT-737, a BH3
      mimetic molecule effective at the mitochondrial level, has been shown to induce
      apoptosis in different human tumoral cell lines as well as in primary patient
      derived cells, and in a mouse xenograph model. METHODS: In this report, we
      analyzed the pro-death effect of ABT-737 on two human retinoblastoma cell lines,
      Y79 and WERI-Rb, as well as on the mouse photoreceptor cell line 661W. RESULTS:
      We observed that ABT-737 was very effective as a single agent in inducing human
      WERI-Rb cells apoptosis without affecting the mouse 661W photoreceptor cells.
      However human Y79 cells were resistant to ABT-737, as a probable consequence of
      the absence of Bax. The high sensitivity of WERI-Rb to ABT-737 can be increased
      by downregulating Mcl-1 using the proteasome inhibitor MG-132. Preliminary
      analysis in primary mouse retinoblastoma tumoral cell lines predicts high
      sensitivity to ABT-737. CONCLUSION: Our data suggest that ABT-737 or related
      compounds could be a highly effective drug in the treatment of some
      retinoblastomas.

PMID- 21955142
TI  - Seizure outcomes following multilobar epilepsy surgery.
AB  - PURPOSE: Outcomes following unilobar surgeries for refractory epilepsy have been
      well described. However, little is known about long-term seizure outcomes
      following multilobar resections. The aim of the current study was to identify
      long-term seizure control and predictors of seizure recurrence in this patient
      population. METHODS: Records of patients who underwent multilobar epilepsy
      surgery at the Cleveland Clinic between 1994 and 2010 were retrospectively
      reviewed. A postoperative follow-up of at least 6 months was required. Patients
      were classified as seizure free if they achieved an Engel class I at last follow
      up. Long-term chances of seizure freedom were illustrated using a survival
      analysis, and predictors of recurrence were identified using Cox proportional
      hazard modeling. KEY FINDINGS: Sixty-three patients with medically intractable
      epilepsy underwent multilobar surgical resections during the study period (mean
      follow-up of 4.6 years). Predominant resection types included extended occipital
      (temporoparietooccipital, parietooccipital, temporooccipital: 57%),
      frontotemporal (21%), and temporoparietal (17%). Mean age at surgery was 21.4
      years and mean age at seizure onset was 10.1 years. Fifty-six percent of the
      patients underwent extraoperative invasive electroencephalography (EEG)
      evaluations. At 6 postoperative months, 71% (95% confidence interval (CI) 65-77)
      were seizure-free (SF), 64% (CI 58-70) were SF at 1 year, 52% (CI 46-59) were SF
      at 5 years, and 41% (CI 32-50) remained SF at 10 years. Forty-one patients had at
      least one breakthrough seizure after surgery (median timing of recurrence 6.1
      months), with an Engel class 1 achieved again by last follow-up in 12 of these 41
      cases. Nine patients required a reoperation. Patients who underwent extended
      occipital/posterior quadrant resections had more favorable outcomes as compared
      to the other groups. With multivariate analysis, the type of resection (p =
      0.03), preoperative auras (p = 0.03), an incomplete resection (0.03), and the
      presence of postoperative spikes (p = 0.0003) correlated with seizure recurrence.
      The risk of seizure recurrence for an incomplete resection was 2.3 (CI 1.53
      3.36), preoperative aura 2.3 (CI 1.34-3.87), and postoperative spikes on surface
      EEG 2.5 (CI 1.29-4.71). SIGNIFICANCE: A favorable outcome can be achieved in 41%
      of patients undergoing multilobar resections for epilepsy surgery at 10 years of
      follow-up. Close to one-third of patients who have breakthrough seizures after
      surgery are able to regain seizure freedom by last follow-up. Predictors of
      recurrence include resection type (frontotemporal and parietotemporal resections
      did worse), presence of preoperative aura, an incomplete surgical resection, and
      the presence of postoperative interictal discharges on EEG.

PMID- 21955143
TI  - Protracted abstinence from distinct drugs of abuse shows regulation of a common
      gene network.
AB  - Addiction is a chronic brain disorder. Prolonged abstinence from drugs of abuse
      involves dysphoria, high stress responsiveness and craving. The neurobiology of
      drug abstinence, however, is poorly understood. We previously identified a unique
      set of hundred mu-opioid receptor-dependent genes in the extended amygdala, a key
      site for hedonic and stress processing in the brain. Here we examined these
      candidate genes either immediately after chronic morphine, nicotine, Delta9
      tetrahydrocannabinol or alcohol, or following 4 weeks of abstinence. Regulation
      patterns strongly differed among chronic groups. In contrast, gene regulations
      strikingly converged in the abstinent groups and revealed unforeseen common
      adaptations within a novel huntingtin-centered molecular network previously
      unreported in addiction research. This study demonstrates that, regardless the
      drug, a specific set of transcriptional regulations develops in the abstinent
      brain, which possibly contributes to the negative affect characterizing
      protracted abstinence. This transcriptional signature may represent a hallmark of
      drug abstinence and a unitary adaptive molecular mechanism in substance abuse
      disorders.

PMID- 21955144
TI  - Chiral pyridin-3-ones and pyridines: syntheses of enantiopure 2,4-disubstituted 6
      hydroxy-1,6-dihydro-2H-pyridin-3-ones, 2,3-disubstituted 4-iodopyridines, and
      enantiopure 2,3-disubstituted 4-pyridinemethanols.
AB  - The development of an innovative method to access enantiopure 2,4-disubstituted 6
      hydroxy-1,6-dihydro-2H-pyridin-3-ones starting from D-glucal via the aza
      Achmatowicz transformation has been described. These highly functionalized
      pyridin-3-ones have been utilized for the synthesis of contiguously substituted
      pyridines through a rapid and efficient Et(3)N/Ac(2)O promoted cyclo-elimination,
      aromatization cascade, allowing the facile assembly of important pyridine-based
      building blocks like 2-substituted 3-acetoxy-4-iodopyridines and enantiopure 2
      substituted 3-acetoxy-4-pyridinemethanols possessing benzylic stereogenic
      centers, whose synthesis otherwise would be tedious. The utilization of
      commercially available sugars as starting materials, mild reaction conditions,
      catalytic transfer hydrogen (CTH) of alpha-furfuryl azide derivatives, transfer
      of chiral aryl/alkyl methanols from enulosides to pyridin-3-ones and pyridines,
      high yields, and short reaction times are key features of this method. The
      utility of the method has been further exemplified by demonstrating the usage of
      the 2-substituted 3-acetoxy-4-iodopyridine for the construction of biologically
      significant molecules like 2,7-disubstituted furo[2,3-c]pyridines and 7,7'
      disubstituted 2,2'-bifuro[2,3-c]pyridines.

PMID- 21955145
TI  - Patterns of mammalian diversification in recent evolutionary times: global
      tendencies and methodological issues.
AB  - Changes in diversification patterns estimated from phylogenetic trees are an
      important source of information about the dynamics of evolution. To study the
      diversification of mammals, we reconstructed phylogenetic trees of 29 families
      and fitted both constant-rate and variable-rate models of diversification. In
      addition, we investigated the effect of clock models and phylogenetic
      reconstruction problems on diversification analyses. We observed, first, that
      none of the families increased its diversification rate during the last few
      million years, including the Pleistocene. Furthermore, we detected a decrease in
      diversification that, after application of different tests, was significant only
      for a minority of families. However, when diversification variation was analysed
      in a combined tree of all families, a global decline in diversification became
      significant. Therefore, although distorted by some methodological artefacts, we
      found an underlying signal of gradually decreasing diversification that suggests
      that ecological factors may have shaped the recent diversification of mammals.

PMID- 21955146
TI  - Multidimensional strategy for sensitive phosphoproteomics incorporating protein
      prefractionation combined with SIMAC, HILIC, and TiO(2) chromatography applied to
      proximal EGF signaling.
AB  - Comprehensive enrichment and fractionation is essential to obtain a broad
      coverage of the phosphoproteome. This inevitably leads to sample loss, and thus,
      phosphoproteomics studies are usually only performed on highly abundant samples.
      Here, we present a comprehensive phosphoproteomics strategy applied to 400 MUg of
      protein from EGF-stimulated HeLa cells. The proteins are separated into membrane
      and cytoplasmic fractions using sodium carbonate combined with
      ultracentrifugation. The phosphopeptides were separated into monophosphorylated
      and multiphosphorylated pools using sequential elution from IMAC (SIMAC) followed
      by hydrophilic interaction liquid chromatography of the mono- and
      nonphosphorylated peptides and subsequent titanium dioxide chromatography of the
      HILIC fractions. This strategy facilitated the identification of >4700 unique
      phosphopeptides, while 636 phosphosites were changing following short-term EGF
      stimulation, many of which were not previously known to be involved in EGFR
      signaling. We further compared three different data processing programs and found
      large differences in their peptide identification rates due to different
      implementations of recalibration and filtering. Manually validating a subset of
      low-scoring peptides exclusively identified using the MaxQuant software revealed
      a large percentage of false positive identifications. This indicates that,
      despite having highly accurate precursor mass determination, peptides with low
      fragment ion scores should not automatically be reported in phosphoproteomics
      studies.

PMID- 21955147
TI  - Factors predicting therapeutic efficacy of combination treatment with sitagliptin
      and metformin in type 2 diabetic patients: the COSMETIC study.
AB  - OBJECTIVE: We assessed the predictive parameters for therapeutic efficacy of
      initial combination therapy with sitagliptin and metformin in drug-naive type 2
      diabetic patients. DeSIGN, PATIENTS, AND MEASUREMENTS: In this 52-week treatment
      study, 150 patients (mean age, 54.9 +/- 12.5 years) with type 2 diabetes and
      HbA1c of 7.0-10% were treated with sitagliptin 100 mg once and metformin 500 mg
      twice daily. To assess the predictive parameters for therapeutic efficacy, a
      multivariate regression analysis was performed with baseline fasting glucose,
      insulin, C-peptide, and glucagon levels, homoeostasis model assessment-insulin
      resistance (HOMA-IR) and beta-cell function (HOMA-B), insulinogenic index (IGI,
      defined as 30-0 min insulin/30-0 min glucose), and area under the curve for
      glucose, insulin, and C-peptide obtained after 75-g oral glucose tolerance test.
      RESULTS: After 52 weeks, mean HbA1c levels and fasting and postload 2-h glucose
      were significantly decreased from 8.7 +/- 1.4% to 7.2 +/- 1.3%, 9.2 +/- 3.0 to
      7.2 +/- 1.8 mm, and 17.5 +/- 5.1 to 10.9 +/- 3.6 mm, respectively (P < 0.01).
      HOMA-B and IGI increased significantly from 50.3 +/- 33.5 to 75.1 +/- 32.8 and
      from 11.3 +/- 1.3 to 35.0 +/- 6.3 at 52 weeks, respectively (P < 0.01).
      Multivariate regression analysis indicated that the reduction in HbA1c was
      significantly associated with high baseline HbA1c, low IGI, and short duration of
      diabetes after adjusting for age, sex, body mass index, blood pressure,
      triglycerides, creatinine, high-sensitivity CRP, glucagon, C-peptide, HOMA-B, and
      HOMA-IR. No severe adverse events were observed. CONCLUSION: These results
      suggest that drug-naive type 2 diabetic patients with low beta-cell function
      would benefit the most from early initial combination therapy of sitagliptin and
      metformin.

PMID- 21955148
TI  - Probabilistic sleep architecture models in patients with and without sleep apnea.
AB  - Sleep fragmentation of any cause is disruptive to the rejuvenating value of
      sleep. However, methods to quantify sleep architecture remain limited. We have
      previously shown that human sleep-wake stage distributions exhibit multi
      exponential dynamics, which are fragmented by obstructive sleep apnea (OSA),
      suggesting that Markov models may be a useful method to quantify architecture in
      health and disease. Sleep stage data were obtained from two subsets of the Sleep
      Heart Health Study database: control subjects with no medications, no OSA, no
      medical co-morbidities and no sleepiness (n = 374); and subjects with severe OSA
      (n = 338). Sleep architecture was simplified into three stages: wake after sleep
      onset (WASO); non-rapid eye movement (NREM) sleep; and rapid eye movement (REM)
      sleep. The connectivity and transition rates among eight 'generator' states of a
      first-order continuous-time Markov model were inferred from the observed
      ('phenotypic') distributions: three exponentials each of NREM sleep and WASO; and
      two exponentials of REM sleep. Ultradian REM cycling was accomplished by imposing
      time-variation to REM state entry rates. Fragmentation in subjects with severe
      OSA involved faster transition probabilities as well as additional state
      transition paths within the model. The Markov models exhibit two important
      features of human sleep architecture: multi-exponential stage dynamics
      (accounting for observed bout distributions); and probabilistic transitions (an
      inherent source of variability). In addition, the model quantifies the
      fragmentation associated with severe OSA. Markov sleep models may prove important
      for quantifying sleep disruption to provide objective metrics to correlate with
      endpoints ranging from sleepiness to cardiovascular morbidity.

PMID- 21955149
TI  - Female sexual dysfunction: facts and factors among gynecology outpatients.
AB  - AIM: This study was aimed at assessing the female sexual dysfunction of
      respondents at gynecology outpatient clinics. MATERIALS AND METHODS:   The cross
      sectional study involved interviewing 137 female respondents from the gynecology
      outpatient department of Dhaka Medical College Hospital and Shaheed Suhrawardy
      Hospital with a semi-structured questionnaire during March-August 2007. The
      sociodemographic details and sexual history with sexual problems were recorded.
      RESULTS: Half (51.8%) the respondents had one or more sexual problems. Pain
      during intercourse (71.8%) and reduced desire (54.9%) were highest among
      different complaints followed by orgasmic (43.66%) and arousal problems (32.39%).
      Age and education were significantly associated with reduced desire (P=0.03).
      Delivery mode was significantly associated with inhibited desire (P=0.01) and
      arousal problems (P=0.003), and not significantly with pain (P=0.06). After
      adjusting confounding factors, parity (odds ratio [OR]=3.4, 95% confidence
      interval [CI]: 1.21-9.68), history of menstrual regulation (OR=2.84, 95%CI: 1.31
      6.22), mental stress (OR=2.81, 95%CI: 1.05-7.50) and sexual problems of the
      husband (OR=3.16, 95%CI: 1.19-8.44) became risk factors for increasing odds of
      having dysfunction while increased frequency of intercourse showed a marginally
      significant reducing effect (OR=0.764, 95%CI: 0.95-1.00). CONCLUSIONS: This is a
      pioneer study in Bangladesh to postulate female sexuality, revealing pain
      disorder as most prevalent; the women with dysfunction were dissatisfied with
      their sexual life. In order to determine the cause of female sexual dysfunction,
      the topic needs further exploration involving intervention at regular medical
      investigations.

PMID- 21955151
TI  - The hyphen as a segmentation cue in triconstituent compound processing: it's
      getting better all the time.
AB  - Inserting a hyphen in Dutch and Finnish compounds is most often illegal given
      spelling conventions. However, the current two eye movement experiments on
      triconstituent Dutch compounds like voetbalbond"footballassociation" (Experiment
      1) and triconstituent Finnish compounds like lentokenttataksi"airporttaxi"
      (Experiment 2) show that inserting a hyphen at constituent boundaries does not
      have to be detrimental to compound processing. In fact, when hyphens were
      inserted at the major constituent boundary (voetbal-bond"football-association";
      lentokentta-taksi"airport-taxi"), processing of the first part
      (voetbal"football"; lentokentta"airport") turns out to be faster when it is
      followed by a hyphen than when it is legally concatenated. Inserting a hyphen
      caused a delay in later eye movement measures, which is probably due to the
      illegality of inserting hyphens in normally concatenated compounds. However, in
      both Dutch and Finnish we found a learning effect in the course of the
      experiment, such that by the end of the experiments hyphenated compounds are read
      faster than in the beginning of the experiment. By the end of the experiment,
      compounds with a hyphen at the major constituent boundary were actually processed
      equally fast as (Dutch) or even faster than (Finnish) their concatenated
      counterparts. In contrast, hyphenation at the minor constituent boundary (voet
      balbond"foot-ballassociation"; lento-kenttataksi"air-porttaxi") was detrimental
      to compound processing speed throughout the experiment. The results imply that
      the hyphen may be an efficient segmentation cue and that spelling illegalities
      can be overcome easily, as long as they make sense.

PMID- 21955152
TI  - Rate-dependent AV nodal function: closely bound conduction and refractory
      properties.
AB  - INTRODUCTION: The atrioventricular node (AV) node conducts slowly and filters
      atrial impulses. Puzzlingly, the recovery (conduction time vs atrial cycle
      length) and refractory curve (His bundle cycle length vs atrial cycle length)
      characterizing AV nodal function undergo disparate rate-dependent changes. We
      sought the functional origin and significance of these disparate changes. METHODS
      AND RESULTS: Differences between the recovery and refractory curve were assessed
      in 30 steady state AV nodal responses (all potential paired combinations between
      5 basic and 6 pretest cycle lengths imposed with S(1)S(2)S(3) protocols) in
      rabbit heart preparations. Five of these responses corresponded to standard
      premature protocols. Both basic and pretest cycle length shortenings increased
      pretest conduction time that in turn equally shortened the ensuing His-atrial
      interval at all test cycle lengths. This effect was mathematically predictable
      and tended to shift the refractory curve downward whereas not affecting the
      recovery curve. Moreover, increases in pretest conduction time also shifted the
      recovery and refractory curve equally rightward on their x-axis, thereby biasing
      curve comparison between steady states. This problem could be overcome with
      equivalent results either by accordingly correcting the atrial cycle length or by
      using the His-atrial interval as the recovery index. CONCLUSION: Recovery and
      refractory curves from AV nodal steady state responses including standard
      premature protocols only differ by the His-atrial interval that decreases with
      the pretest conduction time. The latter also biases curve comparison between
      steady states. Rate-dependent AV nodal function is best assessed with recovery
      curves freed from changes in pretest conduction time.

PMID- 21955150
TI  - Chimeric aptamers in cancer cell-targeted drug delivery.
AB  - Aptamers are single-stranded structured oligonucleotides (DNA or RNA) that can
      bind to a wide range of targets ("apatopes") with high affinity and specificity.
      These nucleic acid ligands, generated from pools of random-sequence by an in
      vitro selection process referred to as systematic evolution of ligands by
      exponential enrichment (SELEX), have now been identified as excellent tools for
      chemical biology, therapeutic delivery, diagnosis, research, and monitoring
      therapy in real-time imaging. Today, aptamers represent an interesting class of
      modern pharmaceuticals which with their low immunogenic potential mimic extend
      many of the properties of monoclonal antibodies in diagnostics, research, and
      therapeutics. More recently, chimeric aptamer approach employing many different
      possible types of chimerization strategies has generated more stable and
      efficient chimeric aptamers with aptamer-aptamer, aptamer-nonaptamer
      biomacromolecules (siRNAs, proteins) and aptamer-nanoparticle chimeras. These
      chimeric aptamers when conjugated with various biomacromolecules like locked
      nucleic acid (LNA) to potentiate their stability, biodistribution, and targeting
      efficiency, have facilitated the accurate targeting in preclinical trials. We
      developed LNA-aptamer (anti-nucleolin and EpCAM) complexes which were loaded in
      iron-saturated bovine lactofeerin (Fe-blf)-coated dopamine modified surface of
      superparamagnetic iron oxide (Fe(3)O(4)) nanoparticles (SPIONs). This complex was
      used to deliver the specific aptamers in tumor cells in a co-culture model of
      normal and cancer cells. This review focuses on the chimeric aptamers, currently
      in development that are likely to find future practical applications in concert
      with other therapeutic molecules and modalities.

PMID- 21955153
TI  - Multivariate analysis of antibody induction therapy and their associated outcomes
      in live donor kidney transplantation in the recent era.
AB  - The majority of kidney transplant recipients in the United States receive
      antibody induction, but its impact on outcomes in living donor transplant is not
      well-described. We used Organ Procurement and Transplant Network/United Network
      for Organ Sharing (OPTN/UNOS) data as of November 2009 to compare acute rejection
      (AR) and graft survival among all primary adult living donor kidney recipients of
      no antibody induction, antithymocyte globulin (ATG) and interleukin-2 receptor
      antagonists (IL-2RA) in an earlier era (1998-2002; n=21,919) and a later era
      (2003-2008, n=26,837). The incidence of AR in the overall cohort decreased from
      18.5% in 1998 to 8% in 2008. From 1998 to 2002, antibody induction was associated
      with a decreased risk of acute rejection at six months (RR 0.67, 95% CI 0.62
      0.72) and one yr (RR 0.71, 0.65-0.76), while in the recent era, induction was not
      associated with acute rejection at six months (RR 0.97, 0.88-1.07) or one yr (RR
      1.01, 0.91-1.10). There was no difference in graft survival over five yr with
      antibody induction in either era. Although antibody induction was associated with
      a decreased risk of AR from 1998 to 2002, it was not associated with a decreased
      risk of acute rejection from 2003 to 2008, nor was it associated with a
      difference in graft survival in either era.

PMID- 21955154
TI  - Case of juvenile pemphigus vulgaris which responded to i.v. immunoglobulin
      therapy.

PMID- 21955155
TI  - The endogenous opioid system in human alcoholics: molecular adaptations in brain
      areas involved in cognitive control of addiction.
AB  - The endogenous opioid system (EOS) plays a critical role in addictive processes.
      Molecular dysregulations in this system may be specific for different stages of
      addiction cycle and neurocircuitries involved and therefore may differentially
      contribute to the initiation and maintenance of addiction. Here we evaluated
      whether the EOS is altered in brain areas involved in cognitive control of
      addiction including the dorsolateral prefrontal cortex (dl-PFC), orbitofrontal
      cortex (OFC) and hippocampus in human alcohol-dependent subjects. Levels of EOS
      mRNAs were measured by quantitative reverse transcription-polymerase chain
      reaction (qRT-PCR), and levels of dynorphins by radioimmunoassay (RIA) in post
      mortem specimens obtained from 14 alcoholics and 14 controls. Prodynorphin mRNA
      and dynorphins in dl-PFC, kappa-opioid receptor mRNA in OFC and dynorphins in
      hippocampus were up-regulated in alcoholics. No significant changes in expression
      of proenkephalin, and u- and delta-opioid receptors were evident; pro
      opiomelanocortin mRNA levels were below the detection limit. Activation of the
      kappa-opioid receptor by up-regulated dynorphins in alcoholics may underlie in
      part neurocognitive dysfunctions relevant for addiction and disrupted inhibitory
      control.

PMID- 21955156
TI  - International consensus clinical practice statements for the treatment of
      neuropsychiatric conditions associated with epilepsy.
AB  - In order to address the major impact on quality of life and epilepsy management
      caused by associated neuropsychiatric conditions, an international consensus
      group of epileptologists met with the aim of developing clear evidence-based and
      practice-based statements to provide guidance on the management of these
      conditions. Using a Delphi process, this group prioritized a list of key
      management areas. These included: depression, anxiety, psychotic disorders,
      nonepileptic seizures, cognitive dysfunction, antiepileptic drug (AED)-related
      neurobehavioral disorders, suicidality, disorders in children and adolescents,
      disorders in children with intellectual disability, and epilepsy surgery.
      Clinical practice statements were developed for each area and consensus reached
      among members of the group. The assessment and management of these conditions
      needs to combine knowledge of psychiatric disorders, knowledge of the impact of
      epilepsy and its treatment on psychopathology, and an ability to deliver care
      within epilepsy services. The aim of these statements is to provide guidance on
      quality care for people with epilepsy that have a range of neuropsychiatric
      disorders.

PMID- 21955157
TI  - Comment on "High levels of bisphenol A in paper currencies from several
      countries, and implications for dermal exposure".

PMID- 21955158
TI  - Molecular modeling: a search for a calpain inhibitor as a new treatment for
      cataractogenesis.
AB  - Studies of 17 analoges of 3 (SJA6017) in an in silico calpain model are
      reconciled to measured IC(50) values against ovine calpain. The studies validate
      the potential of the "model" and criteria established for inhibition as a tool to
      select structures for synthesis to test as calpain inhibitors. Using this
      screening methodology of virtual libraries led us to synthesize several
      inhibitors including macrocycle 33, which in vitro sheep eye lens culture
      experiments showed to substantially slow opacification.

PMID- 21955159
TI  - High rate of incomplete resection after primary excision of eyelid BCC: multi
      staged resection rarely needs more than two procedures.
AB  - PURPOSE: Small, well-demarcated, biopsy-proven periocular basal cell carcinomas
      (BCC) are often excised in a single stage with immediate reconstruction when
      histology or location is considered low-risk. We investigated margin clearance in
      patients undergoing primary excision and immediate reconstruction (PER) versus
      multi-staged fast paraffin excision (MSE) and reviewed risk factors for
      incomplete excision. METHODS: Retrospective, interventional, comparative case
      series of periocular BCCs excised over a 3-year period (2006-2008). RESULTS:
      Ninety consecutive patients with periocular BCC (average age 77 +/- 10.1 years,
      60% females) were included. 39% (35/90) underwent PER with the remainder managed
      by MSE (55/90, 61%). Patients undergoing MSE had larger lesions (38% > 10 mm
      versus 23% PER) which were more likely to involve the medial canthus (25 versus
      11% PER). Incomplete histological clearance was noted in 34% (12/35) patients
      after PER. Only 3/55 (5%) needed third stage of excision in the MSE group with
      final incomplete excision in two cases (3.6%) that did not undergo a third stage
      excision. No significant risk factors were found likely to predict residual BCC
      overall, after first excision stage. Subgroup analysis for patients undergoing
      PER showed multiple lesions as the only statistically significant factor for
      incomplete excision. CONCLUSION: This study shows an unacceptably high rate of
      incomplete resection with primary excision and repair using a standard 3 mm
      margin. The majority of lesions undergoing multi-stage excision required no more
      than two stages for complete removal. Multi-stage excision with histological
      confirmation of clear margins prior to reconstruction is recommended for routine
      management of all periocular BCC.

PMID- 21955160
TI  - A hemoglobin-based multifunctional therapeutic: polynitroxylated pegylated
      hemoglobin.
AB  - Polynitroxylated pegylated hemoglobin (PNPH) as a multifunctional therapeutic
      takes advantage of the ability of hemoglobin (Hb) to transport oxygen, the
      antioxidative stress activities from the redox coupling of nitroxide and heme
      iron, and the hypercolloid properties of pegylation. The published preclinical
      data demonstrating that PNPH acts as a neurovascular protective multifunctional
      therapeutic in an animal model simulating prehospital resuscitation of traumatic
      brain injury (TBI) with hemorrhagic shock (HS) are reviewed. Preliminary results
      on the potential utility of PNPH for neurovascular protection in thrombolytic
      stroke therapy and for correction of vascular dysfunction through transfusion in
      sickle-cell disease (SCD) are also discussed. We hypothesize that with PNPH, Hb
      has more than been tamed--it has become a therapeutic and not just a nontoxic
      extracellular oxygen carrier--and that successful PNPH development as a
      multifunctional therapeutic that protects the neurovasculature and reduces
      oxidative stress may represent a paradigm shift in transfusion and critical care
      medicine, which may meet a number of unmet medical needs resulting from oxidative
      stress and inadequate blood flow, such as HS, TBI, SCD, and stroke.

PMID- 21955161
TI  - Pharmacokinetic evaluation of gemcitabine hydrochloride for the treatment of
      cervical cancer.
AB  - INTRODUCTION: Cervical cancer is the third most prevalent cancer in females
      worldwide. When advanced, the disease requires primary radiation concurrent with
      chemotherapy. However, chemotherapy alone is the standard treatment for
      recurrent/persistent/metastatic disease. AREAS COVERED: Areas covered in this
      review include the treatment of advanced cervical cancer with gemcitabine as
      radiosensitizer, either alone or in combination with cisplatin. The use of
      gemcitabine for recurrent/persistent/metastatic cervical cancer is also reviewed.
      EXPERT OPINION: Statistically significantly better survival rates are achieved
      with cisplatin doublets against cisplatin alone, in the management of
      recurrent/persistent/metastatic cervical cancer. The choice of the cisplatin
      doublet with paclitaxel, vinorelbine, gemcitabine and topotecan arms should be
      based on physician preference, pre-existing morbidity and patient-related
      factors. In advanced disease, a recently reported Phase III trial establishes the
      novel regimen of concurrent gemcitabine plus cisplatin and external radiation,
      followed by brachytherapy and two adjuvant 21-day cycles of gemcitabine plus
      cisplatin, as significantly improving survival outcomes when compared with the
      current standard of care. The increased acute toxicity of this regimen is clear;
      however, this should not deter its incorporation into clinical practice, in that
      the toxicity is predictable and manageable; nevertheless, the occurrence of late
      toxicity and survival at longer follow-up time are reasonable concerns in this
      regimen.

PMID- 21955162
TI  - Function of hyperekplexia-causing alpha1R271Q/L glycine receptors is restored by
      shifting the affected residue out of the allosteric signalling pathway.
AB  - BACKGROUND AND PURPOSE Glycine receptor alpha1 subunit R271Q and R271L
      (alpha1R271Q/L) mutations cause the neuromotor disorder, hereditary
      hyperekplexia. Studies suggest that the 271 residue is located within the
      allosteric signalling pathway linking the agonist binding site to the channel
      gate. The present study aimed to investigate a possible mechanism for restoring
      the function of the alpha1R271Q/L glycine receptor. EXPERIMENTAL APPROACH A 12
      amino-acid segment incorporating the 271 residue on the glycine receptor
      alpha1271Q/L subunit was replaced by the homologous segment from the glycine
      receptor beta subunit (alpha1(Ch) 271Q/L). The function of the alpha1(Ch) 271Q/L
      glycine receptor was examined by whole-cell patch-clamp recording and voltage
      clamp fluorometry techniques. KEY RESULTS The function of the alpha1(Ch) 271Q/L
      glycine receptor was restored to the level of the wild-type (WT) alpha1 glycine
      receptor. Moreover, in the alpha1(Ch) glycine receptor, in contrast to the alpha1
      glycine receptor, the channel function was not sensitive to various substitutions
      of the 271 residue, and the conformational change in the vicinity of the 271
      residue was uncoupled from the channel gating. CONCLUSIONS AND IMPLICATIONS The
      271 residue is shifted out of the allosteric signalling pathway in the alpha1(Ch)
      glycine receptor. We propose that this mechanism provides a novel drug design
      strategy not only for glycine receptor alpha1R271Q/L-caused hereditary
      hyperekplexia, but also for any pathological condition that is caused by missense
      mutation- or covalent modification-induced disorders involving residues in
      allosteric signalling pathways. Such a strategy makes it possible to design an
      ideal drug, which only corrects the function of the mutant or modified protein
      without affecting the WT or naive protein.

PMID- 21955163
TI  - Synthesis, spectroscopic, and in vitro photosensitizing efficacy of
      ketobacteriochlorins derived from ring-B and ring-D reduced chlorins via pinacol
      pinacolone rearrangement.
AB  - In this report, we present a regioselective oxidation of a series
      bacteriochlorins, which on reacting with either ferric chloride (FeCl(3)) or 2,3
      dichloro-5,6-dicyanobenzoquinone (DDQ) yielded the corresponding ring-B or ring-D
      reduced chlorins. The effect of the number of electron-withdrawing groups present
      at the peripheral position, with or without a fused isocyclic ring (ring-E), did
      not make any significant difference in regioselective oxidation of the pyrrole
      rings. However, depending on the nature of substituents, the intermediate bis
      dihydroxy bacteriochlorins on subjecting to pinacol-pinacolone reaction
      conditions gave various ketochlorins. The introduction of the keto-group at a
      particular position in the molecule possibly depends on the stability of the
      intermediate carbocation species. The newly synthesized bacteriochlorins show
      strong long-wavelength absorption and produced significant in vitro (Colon26
      cells) photosensitizing ability. Among the compounds tested, the bacteriochlorins
      containing a keto-group at position 7 of ring-B with cleaved five-member
      isocyclic ring showed the best efficacy.

PMID- 21955165
TI  - Independent distractor frequency and age-of-acquisition effects in picture-word
      interference: fMRI evidence for post-lexical and lexical accounts according to
      distractor type.
AB  - In two fMRI experiments, participants named pictures with superimposed
      distractors that were high or low in frequency or varied in terms of age of
      acquisition. Pictures superimposed with low-frequency words were named more
      slowly than those superimposed with high-frequency words, and late-acquired words
      interfered with picture naming to a greater extent than early-acquired words. The
      distractor frequency effect (Experiment 1) was associated with increased activity
      in left premotor and posterior superior temporal cortices, consistent with the
      operation of an articulatory response buffer and verbal self-monitoring system.
      Conversely, the distractor age-of-acquisition effect (Experiment 2) was
      associated with increased activity in the left middle and posterior middle
      temporal cortex, consistent with the operation of lexical level processes such as
      lemma and phonological word form retrieval. The spatially dissociated patterns of
      activity across the two experiments indicate that distractor effects in picture
      word interference may occur at lexical or postlexical levels of processing in
      speech production.

PMID- 21955164
TI  - Neural evidence for a distinction between short-term memory and the focus of
      attention.
AB  - It is widely assumed that the short-term retention of information is accomplished
      via maintenance of an active neural trace. However, we demonstrate that memory
      can be preserved across a brief delay despite the apparent loss of sustained
      representations. Delay period activity may, in fact, reflect the focus of
      attention, rather than STM. We unconfounded attention and memory by causing
      external and internal shifts of attention away from items that were being
      actively retained. Multivariate pattern analysis of fMRI indicated that only
      items within the focus of attention elicited an active neural trace. Activity
      corresponding to representations of items outside the focus quickly dropped to
      baseline. Nevertheless, this information was remembered after a brief delay. Our
      data also show that refocusing attention toward a previously unattended memory
      item can reactivate its neural signature. The loss of sustained activity has long
      been thought to indicate a disruption of STM, but our results suggest that, even
      for small memory loads not exceeding the capacity limits of STM, the active
      maintenance of a stimulus representation may not be necessary for its short-term
      retention.

PMID- 21955166
TI  - Comparison of the course of biomarker changes and kidney injury in a rat model of
      drug-induced acute kidney injury.
AB  - OBJECTIVE: To aid in evaluating the performance of biomarkers, we measured kidney
      injury biomarkers in rat models of drug-induced acute kidney injury. METHODS AND
      RESULTS: Rats were treated with site-specific nephrotoxins, puromycin,
      gentamicin, cisplatin, or 2-bromoethylamine. Fifteen biomarkers (beta-2
      microglobulin, calbindin, clusterin, cystatin-C, KIM-1, GST-alpha, GST-MU, NGAL,
      osteopontin, EGF, TIMP-1, VEGF, albumin, RPA-1, and urinary total protein) were
      examined in comparison with BUN, serum creatinine, and NAG. Some biomarkers,
      which were different depending in each nephrotoxin, showed ability to detect the
      prodromal stage of drug-induced kidney injury. Characteristic changing patterns
      of biomarkers were also found depending on the specific lesion site in the
      kidney. CONCLUSION: These data suggested that establishment of a suitable
      biomarker panel would facilitate detection of site-specific kidney injury with
      high sensitivity.

PMID- 21955167
TI  - Third-line chemotherapy with tyrosine kinase inhibitor (imatinib mesylate) in
      recurrent ovarian granulosa cell tumor: case report.
AB  - Granulosa cell tumors (GCT) of the ovary represent less than 5% of malignant
      ovarian tumors. Primary treatment of GCT is surgery. GCT present indolent growth
      and also tend to relapse many years after diagnosis. Radiotherapy, chemotherapy
      and hormonal therapy are of little benefit. We report a case of a 60-year-old
      woman with a heavily pretreated recurrent, c-kit positive, GCT of the ovary who
      underwent an experimental therapy with imatinib, a tyrosine kinase inhibitor.
      Imatinib (400 mg/day during the first 2 months; 800 mg/day after) was given,
      without notable side-effects. Monthly positron emission tomography-computed
      tomography scan evaluations were performed revealing a marked reduction of
      disease after 6 months of treatment. To our knowledge this is the first case of
      highly recurrent and unresponsive GCT of the ovary responding to imatinib.
      Further studies evaluating this drug in recurrent and/or aggressive GCT are
      warranted.

PMID- 21955169
TI  - Group structure, kinship, inbreeding risk and habitual female dispersal in plural
      breeding mammals.
AB  - In most plural-breeding mammals, female group members are matrilineal relatives
      but, in a small number of species, all adult females are immigrants who are
      seldom closely related to each other. Some explanations of contrasts in female
      philopatry suggest that these differences are a consequence of variation in
      resource distribution and feeding competition, whereas others argue that they
      reflect variation in the risk of close inbreeding to philopatric females.
      However, neither explanation has been tested against quantitative comparisons.
      Here, we use quantitative comparisons and phylogenetic reconstructions to show
      that contrasts in female philopatry in plural breeders are associated with the
      risk that a female's father is reproductively active in her group when she starts
      to breed, supporting the suggestion that habitual female dispersal has evolved to
      minimize the risk of inbreeding.

PMID- 21955170
TI  - A quantitative analysis of the submentalis muscle electromyographic amplitude
      during rapid eye movement sleep across the lifespan.
AB  - The current definition of rapid eye movement (REM) sleep without atonia has no
      quantitative character, and cut-off values above which the level of
      electromyographic tone can be considered to be 'excessive' are unclear. The aim
      of this study was to analyse the characteristics of chin electromyographic
      amplitude by means of an automatic approach in a large group of normal controls,
      subdivided into different age groups. Eighty-eight normal controls were included,
      subdivided into six age groups: preschoolers (<=6 years); schoolers (6-10 years);
      preadolescents (10-13 years); young adults (24-40 years); middle-aged (58-65
      years); and old (>65 years). The average amplitude of the rectified submentalis
      muscle electromyographic signal was used for the computation of the REM sleep
      Atonia Index. Chin muscle activations were detected, and their amplitude,
      duration and interval analysed. REM sleep Atonia Index showed a progressive and
      rapid increase from the preschool age to school and preadolescent age, reaching
      the maximum in the young adult group; after this age a small decline was observed
      in the middle-aged and old subjects. Conversely, the number of movements per hour
      in REM sleep showed a 'U'-shaped distribution across these age groups, with the
      minimum in the preadolescent group and the two extremes (preschool age and old)
      showing similar average levels of activity. Our results show that REM sleep
      atonia develops continuously during the lifespan, and undergoes complex changes
      with different developmental trajectories for REM atonia and electromyographic
      activations during REM sleep. Different mechanisms might subserve these two
      phenomena and their differential developmental dynamics.

PMID- 21955171
TI  - The role of ultrasound elastography in preoperative localization of parathyroid
      lesions: a new assisting method to preoperative parathyroid ultrasonography.
AB  - BACKGROUND: After the definition of minimally invasive procedures, preoperative
      localization of parathyroid lesions is now crucial. False-positive results up to
      30% were reported by B-mode grayscale ultrasonography (US) in localization of
      parathyroid lesions. Parathyroid adenomas are relatively stiff lesions.
      Ultrasound elastography (USE) can accurately evaluate tissue stiffness and might
      detect the stiff parathyroid lesions. OBJECTIVE: The aim of this study is to
      demonstrate whether USE can detect the level of the stiffness and help the
      preoperative localization of parathyroid lesions during parathyroid
      ultrasonography examination. PATIENTS: The patients who were candidates for
      parathyroidectomy were prospectively enrolled to this study and were evaluated by
      USE. RESULTS: Seventy-two patients with 93 parathyroid lesions underwent
      parathyroidectomy. Sixty-three patients including three multiple endocrine
      neoplasia type-1 patients had primary hyperparathyroidism, three patients with
      chronic renal disease (CRD) had tertiary hyperparathyroidism, three patients with
      CRD and two renal transplanted patients had persistent secondary
      hyperparathyroidism. One patient was excluded. While all parathyroid adenomas
      exhibited high levels of stiffness (score 3 and 4), 17 (63%) out of 27
      parathyroid hyperplasia lesions were shown to have significantly higher
      elasticity. The evaluation of median strain ratios of parathyroid lesions
      revealed that parathyroid adenomas demonstrated significantly higher levels of
      stiffness than hyperplasias (P <= 0.001). CONCLUSIONS: This is the first study
      that evaluates the ultrasound elastographic features of parathyroid lesions.
      Parathyroid adenomas were shown to appear as stiff lesions, and half of the
      hyperplasias showed high elasticity. Parathyroid elastography is a novel
      technique to evaluate parathyroid lesions and might be a guide for surgeons to
      determine the type of operation to apply.

PMID- 21955173
TI  - Psychodynamic change in psychotherapy: cycles of patient-therapist linguistic
      interactions and interventions.
AB  - Psychodynamic change is understood to occur in part through the unique
      therapeutic relationship developed between therapist and patient, and the subtle
      cycles of their conversation from relaxed connection to intense experiencing. The
      Therapeutic Cycles Model (TCM) (Mergenthaler, 1996 ) and Heidelberg Structural
      Change Scale (HSCS) (OPD Task Force, 2008 ) were used to investigate therapist
      patient dynamic processes across 16 sessions of psychotherapy. The TCM identified
      interventions of the therapist instigating change in emotion-abstraction
      patterns. Structural personality change was higher in TCM cycles, and differed
      according to emotion-abstraction patterns. The interventions of the therapist
      promoted dynamic structural change in the patient. The findings demonstrate for
      the first time the interconnection between specific types of therapist and
      patient dialogue that promote deep changes.

PMID- 21955174
TI  - Thromboembolic risk evaluation in patients with atrial fibrillation using a
      modified CHADS(2) scoring system.
AB  - BACKGROUND: Antithrombotic recommendations for relatively low risk patients with
      atrial fibrillation (AF) are not well established. Some patients with CHADS(2)
      score = 0 have a CHA(2) DS(2) -VASc score of 2, which indicated warfarin therapy
      in the latter system. We evaluated the thromboembolic risk in AF patients with a
      CHADS(2) score of 0 or 1. METHODS: A total of 695 patients with AF that were
      followed for >= 12 months (median 65.6 months, range 12-138 months), were
      analyzed retrospectively. The modified CHADS(2) score (MCS) was applied as
      follows. Each CHADS(2) score group was divided into 2 groups, A and B (i.e., MCS
      0A vs 0B, and MCS 1A vs 1B) according to the number of nonmajor risk factors
      (female gender, chronic kidney disease, coronary artery disease, age 65-74
      years). Group A had 0 or 1, and group B had 2 or more nonmajor risk factors.
      RESULTS: In patients with CHADS(2) score = 1, there were 13 thromboembolic events
      (0.65%/year) in 343 MCS 1A patients, and 12 thromboembolic events (1.90%/year) in
      108 MCS 1B patients. Thromboembolic risk was significantly higher in the MCS 1B
      compared to the MCS 1A patients (P = 0.006). In 244 patients with CHADS(2) score
      = 0, the thromboembolic risk of MCS 0B was similar to that of MCS 0A (P = 0.095),
      and 26 patients had a CHA(2) DS(2) -VASc score of 2. CONCLUSION: Patients with
      MCS 1B had a higher thromboembolic risk than patients with MCS 1A. Antithrombotic
      strategies for patients with a CHA(2) DS(2) -VASc score of 2 but a CHADS(2) score
      of 0 need further investigation.

PMID- 21955175
TI  - A community-based study of barriers to HIV care initiation.
AB  - Timely treatment of HIV infection is a public health priority, yet many HIV
      positive persons delay treatment initiation. We conducted a community-based study
      comparing HIV-positive persons who received an HIV diagnosis at least 3 months
      ago but had not initiated care (n=100) with a reference population of HIV
      positive persons currently in care (n=115) to identify potential barriers to
      treatment initiation. Study participants were mostly male (78.0%), and persons of
      color (54.9% Latino, 26.3% black), with median age 37.8 years. Median time since
      HIV diagnosis was 3.7 years. Univariate analysis revealed that those never in
      care differed substantially from those currently in care with regard to
      sociodemographics; HIV testing and counseling experiences; perceived barriers to
      care; and knowledge, attitudes, and beliefs regarding HIV. Factors independently
      associated with never initiating HIV care were younger age (adjusted odds ratio
      [AOR]=0.93; 95% confidence interval [CI]: 0.88, 0.99), shorter time since
      diagnosis (AOR=0.87; 95% CI: 0.77, 0.98), lacking insurance (AOR=0.11; 95% CI:
      0.03, 0.35), not knowing someone with HIV/AIDS (AOR=0.09; 95% CI: 0.03, 0.30) not
      disclosing HIV status (AOR=0.13; 95% CI: 0.02, 0.70), not receiving help making
      an HIV care appointment after diagnosis (AOR=0.04; 95% CI: 0.01, 0.14), and not
      wanting to think about being HIV positive (AOR=3.57; 95% CI: 1.22, 10.46). Our
      findings suggest that isolation and stigma remain significant barriers to
      initiating HIV care in populations consisting primarily of persons of color, and
      that direct linkages to HIV care at the time of diagnosis are critical to
      promoting timely care initiation in these populations.

PMID- 21955177
TI  - Long-term renal function and survival of renal transplant recipients admitted to
      the intensive care unit.
AB  - INTRODUCTION: We determined the long-term mortality and renal allograft function
      of renal transplant recipients admitted to the intensive care unit (ICU).
      METHODS: A single institution retrospective observational cohort study of all
      renal transplant patients admitted to the ICU was performed. Serum creatinine was
      recorded up to one yr after hospital discharge and survival data were collected
      for three yr. RESULTS: Chest sepsis was the commonest reason for ICU admission.
      ICU and hospital mortality were 32% and 19% respectively. Predictors of hospital
      mortality included the presence of sepsis and duration of mechanical ventilation
      (MV). Of the patients who were discharged from ICU, three-yr mortality was 50%.
      Renal function at one yr was worse than that at hospital discharge and at
      baseline, though not statistically significant. Death-censored allograft loss was
      11% over the three-yr follow up period. CONCLUSIONS: Sepsis and requirement for
      MV are independent predictors of mortality in renal transplant recipients
      admitted to ICU. Renal transplant recipients with chest sepsis may warrant
      earlier ICU admission. Any loss of renal allograft function during an episode of
      critical illness appears to have a lasting effect, and longterm patient and
      allograft survival is poor.

PMID- 21955178
TI  - Tunable self-assembly of genetically engineered silk--elastin-like protein
      polymers.
AB  - Silk--elastin-like protein polymers (SELPs), consisting of the repeating units of
      silk and elastin blocks, combine a set of outstanding physical and biological
      properties of silk and elastin. Because of the unique properties, SELPs have been
      widely fabricated into various materials for the applications in drug delivery
      and tissue engineering. However, little is known about the fundamental self
      assembly characteristics of these remarkable polymers. Here we propose a two-step
      self-assembly process of SELPs in aqueous solution for the first time and report
      the importance of the ratio of silk-to-elastin blocks in a SELP's repeating unit
      on the assembly of the SELP. Through precise tuning of the ratio of silk to
      elastin, various structures including nanoparticles, hydrogels, and nanofibers
      could be generated either reversibly or irreversibly. This assembly process might
      provide opportunities to generate innovative smart materials for biosensors,
      tissue engineering, and drug delivery. Furthermore, the newly developed SELPs in
      this study may be potentially useful as biomaterials for controlled drug delivery
      and biomedical engineering.

PMID- 21955179
TI  - Out-of-office and central blood pressure for risk stratification: a cross
      sectional study in patients treated for hypertension.
AB  - BACKGROUND: Central blood pressure (BP) predicts mortality independent of office
      brachial BP. Whether central BP may be useful to differentiate BP control
      requires examination and was the first aim of this study. Secondly, we sought to
      determine the variability in central BP among patients from different categories
      of BP control [controlled hypertension (CH), masked hypertension (MH), white coat
      (WCHT) and uncontrolled hypertension (UH)]. MATERIALS AND METHODS: We assessed
      patients with uncomplicated hypertension using measurement of central BP
      (SphygmoCor 8.1), brachial BP and 24-h ambulatory BP monitoring. BP control was
      defined according to guidelines using office BP and 24-h BP. RESULTS: Of the 201
      patients (63 +/- 8 years, 51% men), 67 (33%) were classified as CH; 59 (29%) with
      MH; 31 (15%) with WCHT; and 44 (22%) with UH. There were no differences in
      central BP parameters (augmentation pressure, augmentation index, pulse pressure)
      between patients with CH and MH or between patients with WCHT and UH (P > 0.05
      for all). However, there was significant overlap in central systolic BP between
      BP control categories. For example, 27% of patients with normal brachial systolic
      BP had central systolic BP above age- and gender-specific normal values,
      including patients from three classifications of BP control (CH: n = 27; MH: n =
      22; and WCHT: n = 4). CONCLUSION: Office central BP alone cannot delineate
      categories of BP control. However, given the high degree of variability in
      central BP among patients from different categories of BP control, measurement of
      central BP may result in significant reclassification of risk related to BP.

PMID- 21955180
TI  - The glycine reuptake inhibitor Org24598 and acamprosate reduce ethanol intake in
      the rat; tolerance development to acamprosate but not to Org24598.
AB  - Extracellular glycine modulates accumbal dopamine levels as well as ethanol
      induced dopamine overflow. Glycine availability is also crucial for regulating
      alcohol consumption and the glycine transporter 1 (GlyT-1) inhibitor Org25935
      robustly decreases alcohol intake in rats. To explore whether the alcohol-intake
      reducing effect of Org25935 is substance bound, we examined the effect of a
      different selective GlyT-1 inhibitor, Org24598, on ethanol consumption in rats
      and compared the effect with that of acamprosate, a drug currently in clinical
      use. We studied the effects of daily Org24598 and acamprosate injections on male
      Wistar rats with ~60% ethanol preference in a limited access two bottle free
      choice model for 12 days, followed by alcohol deprivation for 14 days before a
      second test period of 10 days. Finally, rats underwent in vivo microdialysis
      where dopamine, glycine, taurine and beta-alanine in n. accumbens were measured.
      Org24598 profoundly reduced ethanol intake and the effect remained throughout
      both treatment periods. Acamprosate promptly reduced ethanol intake, but on the
      third day tolerance developed to this effect and acamprosate failed to influence
      alcohol consumption during the second test period. Neither Org24598 nor
      acamprosate reduced water intake. Following the drinking study, the Org24598
      group displayed higher basal accumbal dopamine levels compared with acamprosate
      and vehicle groups. Both Org24598 and acamprosate reduced the ethanol-induced
      dopamine response in n. accumbens. The study demonstrates a robust anti-alcohol
      intake effect of the GlyT-1 inhibitor Org24598, supporting the new concept that
      GlyT-1 inhibition reduces ethanol consumption. GlyT-1 inhibition may represent a
      new treatment principle for alcoholism that is superior to acamprosate.

PMID- 21955182
TI  - Tri-leaflet valve design with a purge flow for heart-assist devices: an in vitro
      optimization study.
AB  - The objective of this study is to assess the effect of a purge flow on valves of
      pulsatile heart-assist devices. Clinical applications of these devices are still
      limited because of frequent thromboembolic complications. These complications
      often originate at the valves and the unavoidable flow separation regions that
      are found behind the leaflets. The flow separations cause a long residence time
      of blood that is considered particularly detrimental. To solve this problem, a
      valve with a purge flow is proposed. A purge flow is a jet, which is separated
      from the main blood flow and directed behind the leaflets into the sinus to flush
      it. Even though the purge flow does not prevent a flow separation, it shortens
      the residence time of the blood in the sinus. Thus, the purge flow improves the
      periodic washout of the blood in the region of flow separation. The complex purge
      flow was investigated in a tri-leaflet valve. The geometrical parameters of the
      valve were varied systematically. A statistical technique--the Taguchi method-
      was used to reduce the number of investigated models to 12. The flows through the
      resulting valve models were numerically simulated and analyzed. The evaluated
      models with the best results were subsequently investigated experimentally using
      different methods: hemodynamic tests in a valve tester and flow visualization
      using the dye washout method. It was shown that the purge flow can effectively
      wash out the sinus. Therefore, the purge flow valve reduces the potential of a
      thrombus formation normally associated with the valve.

PMID- 21955183
TI  - A Lewis basicity scale in dichloromethane for amines and common nonprotogenic
      solvents using a zinc(II) Schiff-base complex as reference Lewis acid.
AB  - A consistent, reliable scale of Lewis basicity in dichloromethane for 26 bases,
      involving amines and nonprotogenic solvents, is presented. A Lewis acidic Zn(II)
      Schiff-base complex, involving formation of stable 1:1 adducts is used as
      reference acid. Evaluation of binding constants is achieved from
      spectrophotometric titrations, by the least-squares nonlinear regression of
      multiwavelength spectrophotometric data. This Lewis basicity scale represents a
      unique set of data reflecting the actual Lewis basicity with respect this "real
      world" Lewis acidic species. The comparison of present Lewis basicity scale with
      data reported in the literature indicates that while for the involved solvents
      their relative basicity is scarcely affected by the reference Lewis acid, in
      contrast for sterically encumbered amines the Lewis basicity seems to be
      dependent from the reference species. Thus, Lewis basicity is governed by the
      steric hindrance at the donor atom and involves very different relative
      basicities than those predicted considering typical reference Lewis acids. This
      is expected to have a major involvement in the organic synthesis and catalysis,
      given the sterically encumbered nature of commonly involved Lewis acidic
      organometallic complexes.

PMID- 21955184
TI  - Mycobacterium shigaense sp. nov., a novel slowly growing scotochromogenic
      mycobacterium that produced nodules in an erythroderma patient with severe
      cellular immunodeficiency and a history of Hodgkin's disease.
AB  - A novel slow-growing scotochromogenic mycobacterium was isolated from skin
      biopsies from a patient with a history of Hodgkin's disease and severe cellular
      immunodeficiency as an opportunistic pathogen. Clinical characterization of these
      lesions revealed papules and nodules with pathological granuloma formation.
      Genotypic analysis using 16S rRNA misidentified this isolate as Mycobacterium
      simiae. However, multiple gene analysis using the internal transcribed spacer
      between the 16S and 23S rRNA genes, and the rpoB and hsp65 genes revealed the
      presence of a novel mycobacterium. The antimicrobial susceptibility of this
      isolate was completely different from that of M. simiae. On the basis of these
      findings, we propose naming this new species Mycobacterium shigaense sp. nov.,
      and conclude that multiple gene analysis is required for the appropriate
      diagnosis and treatment of non-tuberculous mycobacterial infections.

PMID- 21955185
TI  - Simultaneous quantification of 19 drugs/metabolites in urine important for pain
      management by liquid chromatography-tandem mass spectrometry.
AB  - BACKGROUND: Monitoring pain management drugs and frequently abused drugs is
      important for physicians to assess patient compliance. Liquid chromatography
      tandem mass spectrometry offers high specificity needed for this purpose. In this
      report, a novel liquid chromatography-tandem mass spectrometry method for
      simultaneously monitoring 19 drugs/metabolites in urine was developed and
      validated. METHODS: Sample preparation included hydrolysis, dilution and
      turbulent flow online extraction. Analysis was achieved by reverse phase liquid
      chromatography and triple-quadruple tandem mass spectrometry. Two fragment ions,
      one for quantification and the other for assuring identification, were monitored
      for each analyte. RESULTS: No matrix effect or interference was observed. Lower
      limits of quantification ranged from 5 to 25 ng/mL. Within the linear range,
      analytical recovery was between 85.8% and 119.4%. Intra-assay and total
      coefficient of variations were between 0.2% and 12.7%. This method was compared
      with mass spectrometry methods offered by two other laboratories using 82 patient
      samples and 60 spiked urine samples showing 60%-100% agreement. The current
      method identified more positive samples for all analytes except THCA. The
      discrepancy in detection rates was primarily due to the different cut-offs used
      by the other laboratories. CONCLUSIONS: A sensitive and specific liquid
      chromatography-tandem mass spectrometry method was developed for measuring 19
      drugs/metabolites in urine important for pain management clinics.

PMID- 21955187
TI  - Comparison of two point-of-care testing (POCT) devices for fetal lactate during
      labor.
AB  - BACKGROUND: Point-of-care testing (POCT) of fetal scalp blood lactate is used as
      an alternative for pH analysis. Lactate measurements have not been standardized
      and values vary with each device used. The aim of this study was to evaluate the
      performance of two POCT lactate meters for intrapartum use. METHODS: Analytical
      performance of StatStrip Lactate (Nova Biomedical) and Lactate Pro (Arkray) was
      evaluated using CLSI EP10. Both POCT meters were compared with our lactate
      reference method (RapidLab 860; Siemens Healthcare Diagnostics) using fetal scalp
      and neonatal cord blood. Deming regression analysis was performed. RESULTS:
      StatStrip Lactate coefficients of variation (CVs) were 5.1%, 5.0% and 2.6% at
      0.9, 7.5 and 14.1 mmol/L lactate, respectively. CVs for Lactate Pro were 10.7%,
      5.2% and 5.7% at 1.7, 4.1 and 6.4 mmol/L lactate, respectively. Consecutive
      lactate measurements in 37 fetal scalp and 122 cord blood samples revealed
      different test characteristics for the two POCT devices. In fetal scalp blood:
      StatStrip Lactate=1.13*RapidLab-0.39 (R(2)=0.907) and Lactate Pro=0.95*RapidLab
      0.03 (R(2)=0.823). In cord artery blood: StatStrip Lactate=1.08*RapidLab-0.09
      (R(2)=0.810) and Lactate Pro=0.72*RapidLab+0.59 (R(2)=0.807). CONCLUSIONS:
      Overall performance of both Lactate Pro and StatStrip Lactate was good, with
      StatStrip Lactate having smallest CVs and closest correlation to our reference
      method. Both StatStrip Lactate and Lactate Pro can be used as a lactate POCT
      device for obstetric use.

PMID- 21955188
TI  - Treatment advances for glioblastoma.

PMID- 21955189
TI  - Screening for dementia: an opportunity for debate.

PMID- 21955190
TI  - Epidural stimulation of the spinal cord in spinal cord injury: current status and
      future challenges.

PMID- 21955192
TI  - Use of memantine for the treatment of dementia.
AB  - The term 'dementia' encompasses a number of neurodegenerative diseases of which
      Alzheimer's disease (AD) is the most common. Prior to 2003, cholinesterase
      inhibitors, such as donezepil, were the only class of drugs approved to treat
      mild-to-moderate AD. In 2003, memantine became the first drug approved by the US
      FDA to treat moderate-to-severe AD. Currently, both memantine and donepezil are
      FDA approved for the treatment of moderate-to-severe AD. This article examines
      the pharmacologic profile of memantine, evidence for memantine's efficacy in
      moderate-to-severe AD and other dementias, its novel use in other
      neuropsychiatric disorders and future implications and research directions for
      memantine.

PMID- 21955193
TI  - Neuro-oncology: a selected review of ASCO 2011 abstracts.
AB  - American Society of Clinical Oncology (ASCO), the largest clinical oncology
      meeting in the USA, meets annually and consistently provides an exciting forum to
      present new cancer clinical trials and research data. The ASCO 2011 neuro
      oncology session, comprising of 3 days of presentations and over 100 abstracts,
      provided an overview of neuro-oncology, including both metastatic diseases of the
      CNS and primary brain tumors. This brief article attempts to highlight select
      abstracts presented at this years meeting in an organizational manner that will
      hopefully provide a portrait of the large and multifaceted meeting.

PMID- 21955194
TI  - Recent advances in headache research.
AB  - The understanding of the pathophysiology of primary headache disorders,
      especially migraine, has substantially improved over the last two decades. As a
      result, migraine is now mainly considered to be a disorder of the brain, rather
      than the vasculature or the meninges. In addition, the insights of the complex
      pathophysiological mechanisms and the brain structures involved in the disease
      facilitate the development of new therapeutic approaches. At the recent Annual
      Meeting of the American Headache Society in Washington (DC, USA) the latest
      scientific advances, as well as their clinical implications, were highlighted.

PMID- 21955195
TI  - Evaluation of the use of sumatriptan-naproxen sodium for menstrual migraine and
      dysmenorrhea.
AB  - Menstrual migraine (MM) is a form of headache that tends to occur with prolonged,
      intense and extremely disabling attacks in a short period around the menstrual
      cycle (usually 2 days before to 3 days after the onset of the menstrual flow). At
      least 50% of the female migraine population suffers from this subtype of
      migraine. The possible presence of other perimenstrual pain, such as
      dysmenorrhea, can make the attacks even more disabling. Since both of these
      conditions have a common pathological background consisting of a secretion of
      abnormally high levels of prostaglandins, it can be particularly useful to use a
      combination of sumatriptan, the progenitor of the triptans and the drug of choice
      in the treatment of migraine attack, and naproxen sodium, a potent inhibitor of
      prostaglandin biosynthesis. The combination of sumatriptan 85 mg and naproxen
      sodium 500 mg has been tested in women suffering from MM and dysmenorrhea, and
      this combination has been shown to achieve greater satisfaction when compared
      with placebo. Moreover, sumatriptan-naproxen was also better than placebo in
      reducing functional disability and improving productivity. The study is discussed
      in the context of the current state of knowledge about MM treatment.

PMID- 21955196
TI  - Efficacy and tolerability of ramelteon in a double-blind, placebo-controlled,
      crossover study in Japanese patients with chronic primary insomnia.
AB  - The aim of this study was to evaluate the efficacy and safety of ramelteon 4, 8,
      16 or 32 mg and placebo in Japanese patients with chronic insomnia using a
      randomized, double-blind, five-period crossover design. A total of 65 Japanese
      patients with chronic primary insomnia received ramelteon or placebo for two
      nights each in sleep laboratories. Changes in sleep parameters were assessed
      objectively by polysomnography and subjectively by postsleep questionnaires.
      Safety and tolerability was evaluated by assessment of the occurrence of adverse
      events, next-day residual effects and laboratory and ECG investigations.
      Ramelteon 8 and 32 mg significantly shortened the mean latency to persistent
      sleep in comparison with placebo, and there was a statistically significant trend
      for linear dose-response for this sleep parameter. Overall changes in sleep
      architecture were modest (<3% changes vs placebo), with increases in stage 1 and
      decreases in stage 3/4. Ramelteon was well tolerated, the most common adverse
      effect being somnolence, which was similar to placebo at doses up to 8 mg, but
      increased with higher doses. Next-day residual effects occurred no more
      frequently with ramelteon at any dose than with placebo. When compared with sleep
      latency data from a similarly-designed US study, there was no evidence of any
      ethnic differences in the efficacy of ramelteon between Japanese and US patients.
      Overall, ramelteon 8 mg showed the most favorable balance between sleep-promoting
      effects and tolerability. The unique efficacy profile of ramelteon, promoting
      sleep initiation without affecting other sleep parameters, may be due to its
      circadian shifting effect.

PMID- 21955197
TI  - Role of isocitrate dehydrogenase in glioma.
AB  - Recently, the isocitrate dehydrogenase (IDH) enzymes have become a focal point
      for research aimed at understanding the biology of glioma and identifying novel
      targets for therapy. Following the publication of a landmark genetic sequencing
      study in 2008, which identified IDH1 as a frequently mutated gene in
      glioblastoma, much work has been carried out to further characterize the
      frequency, associations and clinical implications of IDH1/2 mutations. Mutations
      in IDH genes are thought to occur early in tumorigenesis and define a subgroup of
      glioma that are characterized by specific metabolic changes and improved
      prognosis. At present, assays identifying tumors with IDH1 mutations are
      clinically useful as prognostic markers. While the mechanisms linking IDH1/2
      mutations to tumor development are still under investigation, the cellular milieu
      created by these mutations offers potential targets for the development of novel
      therapeutics.

PMID- 21955198
TI  - Progress towards personalized therapeutics: biologic- and risk-directed therapy
      for neuroblastoma.
AB  - Neuroblastoma, a tumor of the developing peripheral sympathetic nervous system,
      is the most common and deadly extracranial solid tumor of childhood. Risk
      stratification and risk-adapted therapy play a large role in the modern treatment
      of neuroblastoma. Recently, through extensive international collaboration, new
      guidelines for risk stratification have emerged that will aid in international
      cooperative studies, as well as clarifying therapeutic options for patients.
      Current therapies for low- and intermediate-risk neuroblastoma have resulted in
      excellent prognoses for these risk strata, and current efforts are concentrated
      on chemotherapy reduction. By contrast, much more gradual progress has been made
      in improving survival for high-risk neuroblastoma patients, despite significant
      chemotherapy intensification. Current investigations focus on overcoming
      resistance by elucidating the molecular/genetic causes of neuroblastoma
      tumorigenesis and progression, with the aim of developing more effective
      biologically targeted therapies for this disease.

PMID- 21955199
TI  - Medical treatment of recurrent meningiomas.
AB  - Meningiomas are the second most common primary brain tumor and are primarily
      treated with surgery (with or without embolization) and radiotherapy.
      Increasingly today, meningiomas undergo multiple resections and two radiotherapy
      treatments (either stereotactic or conventional external beam) before
      consideration for hormonal, chemotherapy or targeted therapy. The failure of
      hormonal and cytotoxic chemotherapy in the treatment of recurrent meningioma and
      increasing understanding of potential molecular targets in meningioma has
      resulted in multiple studies utilizing single-agent targeted therapy directed at
      biologically relevant signaling pathways, such as somatostatin (Sandostatin((r))
      LAR, SOM230c), PDGF (imatinib), EGF (erlotinib) and VEGF (sunitinib and
      vatalanib). Early results using a targeted approach have been modest at best and
      are often associated with significant toxicity. Consequently and at present, the
      brain tumor guidelines recognize only three medical therapies for inoperable and
      radiation-refractory meningiomas: hydroxyurea, IFN-alpha and Sandostatin LAR, a
      somatostatin analogue. Clearly, there remains an unmet need in neuro-oncology
      with respect to the medical treatment of recurrent meningiomas.

PMID- 21955200
TI  - Management of von Hippel-Lindau disease-associated CNS lesions.
AB  - Patients with von Hippel-Lindau disease (VHL) often harbor significant disease
      burden within the CNS, specifically craniospinal-axis hemangioblastomas and
      endolymphatic sac tumors (ELSTs). The majority (60-80%) of patients with VHL
      harbor hemangioblastomas, and 10-15% will develop ELSTs. Advances in the
      understanding of the natural history and outcomes associated with the surgical
      management of VHL-associated tumors have led to improved management of patients
      with VHL. Optimizing indications for surgical intervention and refining of
      surgical techniques for these lesions can reduce patient morbidity associated
      with the management of this syndrome. In this article, we review the various
      aspects of perioperative management of patients with VHL, surgical indications
      and general operative principles for the management of hemangioblastomas and
      ELSTs, and outcomes associated with the surgical treatment of these tumors.

PMID- 21955202
TI  - A lifetime of attention-deficit/hyperactivity disorder: diagnostic challenges,
      treatment and neurobiological mechanisms.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a common, early-onset and
      enduring neuropsychiatric disorder characterized by developmentally inappropriate
      deficits in attention, hyperactivity, increased impulsivity and emotional
      dysregulation, resulting in impairments in multiple domains of personal and
      professional life. ADHD has long been considered a disorder of childhood that
      resolves gradually with maturation during adolescence; however, this view was
      contested by systematic follow-up studies documenting the persistence of ADHD
      across the lifespan. In this article, we present converging evidence from
      clinical and genetic studies arguing for a remarkable perseverance of ADHD
      related symptomatology, taking into account the disorder's variable and changing
      phenotype moderated by a high rate of comorbidity throughout the lifecycle. We
      also cover findings highlighting alterations in structural and functional
      neuroanatomy based on neuropsychological, psychophysiological and brain imaging
      approaches, and discuss options for deficit-focused pharmacological and
      psychotherapeutic interventions at different stages of life. In addition, we
      develop a fusion model of disease risk underlying the pathway to ADHD etiology.
      Finally, we argue for large-scale, systematic studies to explore factors
      predicting the long-term outcome of the disease and the possibilities to exploit
      those predictors with more personalized treatment strategies to enhance
      remittance and/or coping.

PMID- 21955203
TI  - Childhood leukodystrophies: a clinical perspective.
AB  - Leukodystrophies are white matter disorders that are genetic in nature. In the
      young, they represent an important cause of progressive neurological disability.
      They are frequently recognized on MRI, but their identification remains a
      challenge. Their diagnosis is important for prognostication, palliative and
      experimental treatment, as well as family screening. The diagnostic strategy
      rests upon clinical clues and MRI patterns, complemented by appropriately
      selected electrophysiological and laboratory testing. Considerable overlap exists
      between white and gray matter disease, as neuronal degeneration will result in
      myelin loss. An understanding of the pathophysiology and natural disease
      evolution is necessary to understand the risks and benefits of experimental and
      palliative treatments.

PMID- 21955201
TI  - An update on the pharmacotherapy of attention-deficit/hyperactivity disorder in
      adults.
AB  - Adults with attention-deficit/hyperactivity disorder (ADHD) are more frequently
      presenting for diagnosis and treatment. Medication is considered to be
      appropriate among available treatments for ADHD; however, the evidence supporting
      the use of pharmacotherapeutics for adults with ADHD remains less established. In
      this article, the effectiveness and dosing parameters of the various agents
      investigated for adult ADHD are reviewed. In adults with ADHD, short-term
      improvements in symptomatology have been documented through the use of stimulants
      and antidepressants. Studies suggest that methylphenidate and amphetamine
      maintained an immediate onset of action, whereas the ADHD response to the
      nonstimulants appeared to be delayed. At a group level, there appears to be some,
      albeit not entirely consistent, dose-dependent responses to amphetamine and
      methylphenidate. Generally speaking, variability in diagnostic criteria, dosing
      parameters and response rates between the various studies was considerable, and
      most studies were of a relatively short duration. The aggregate literature shows
      that the stimulants and catecholaminergic nonstimulants investigated had a
      clinically significant beneficial effect on treating ADHD in adults.

PMID- 21955207
TI  - Geographical variation in allometry in the guppy (Poecilia reticulata).
AB  - Variation in static allometry, the power relationship between character size and
      body size among individuals at similar developmental stages, remains poorly
      understood. We tested whether predation or other ecological factors could affect
      static allometry by comparing the allometry between the caudal fin length and the
      body length in adult male guppies (Poecilia reticulata) among populations from
      different geographical areas, exposed to different predation pressures. Neither
      the allometric slopes nor the allometric elevations (intercept at constant slope)
      changed with predation pressure. However, populations from the Northern Range in
      Trinidad showed allometry with similar slopes but lower intercepts than
      populations from the Caroni and the Oropouche drainages. Because most of these
      populations are exposed to predation by the prawn Macrobrachium crenulatum, we
      speculated that the specific selection pressures exerted by this predator
      generated this change in relative caudal fin size, although effects of other
      environmental factors could not be ruled out. This study further suggests that
      the allometric elevation is more variable than the allometric slope.

PMID- 21955206
TI  - Thiocolchicoside suppresses osteoclastogenesis induced by RANKL and cancer cells
      through inhibition of inflammatory pathways: a new use for an old drug.
AB  - BACKGROUND AND PURPOSE: Most patients with cancer die not because of the tumour
      in the primary site, but because it has spread to other sites. Common tumours,
      such as breast, multiple myeloma, and prostate tumours, frequently metastasize to
      the bone. To search for an inhibitor of cancer-induced bone loss, we investigated
      the effect of thiocolchicoside, a semi-synthetic colchicoside derived from the
      plant Gloriosa superba and clinically used as a muscle relaxant, on
      osteoclastogenesis induced by receptor activator of NF-kappaB ligand (RANKL) and
      tumour cells. EXPERIMENTAL APPROACH: We used RAW 264.7 (murine macrophage) cells,
      a well-established system for osteoclastogenesis, and evaluated the effect of
      thiocolchicoside on RANKL-induced NF-kappaB signalling and osteoclastogenesis as
      well as on osteoclastogenesis induced by tumour cells. KEY RESULTS:
      Thiocolchicoside suppressed osteoclastogenesis induced by RANKL, and by breast
      cancer and multiple myeloma cells. Inhibition of the NF-kappaB pathway was
      responsible for this effect since the colchicoside inhibited RANKL-induced NF
      kappaB activation, activation of IkappaB kinase (IKK) and suppressed inhibitor of
      NF-kappaBalpha (IkappaBalpha) phosphorylation and degradation, an inhibitor of NF
      kappaB. Furthermore, an inhibitor of the IkappaBalpha kinase gamma or NF-kappaB
      essential modulator, the regulatory component of the IKK complex, demonstrated
      that the NF-kappaB signalling pathway is mandatory for osteoclastogenesis induced
      by RANKL. CONCLUSIONS AND IMPLICATIONS: Together, these data suggest that
      thiocolchicoside significantly suppressed osteoclastogenesis induced by RANKL and
      tumour cells via the NF-kappaB signalling pathway. Thus, thiocolchicoside, a drug
      that has been used for almost half a century to treat muscle pain, may also be
      considered as a new treatment for bone loss.

PMID- 21955208
TI  - Systematic structure modifications of imidazo[1,2-a]pyrimidine to reduce
      metabolism mediated by aldehyde oxidase (AO).
AB  - N-{trans-3-[(5-Cyano-6-methylpyridin-2-yl)oxy]-2,2,4,4
      tetramethylcyclobutyl}imidazo[1,2-a]pyrimidine-3-carboxamide (1) was recently
      identified as a full antagonist of the androgen receptor, demonstrating excellent
      in vivo tumor growth inhibition in castration-resistant prostate cancer (CRPC).
      However, the imidazo[1,2-a]pyrimidine moiety is rapidly metabolized by aldehyde
      oxidase (AO). The present paper describes a number of medicinal chemistry
      strategies taken to avoid the AO-mediated oxidation of this particular system.
      Guided by an AO protein structure-based model, our investigation revealed the
      most probable site of AO oxidation and the observation that altering the
      heterocycle or blocking the reactive site are two of the more effective
      strategies for reducing AO metabolism. These strategies may be useful for other
      drug discovery programs.

PMID- 21955210
TI  - Intrapartum translabial ultrasound demonstration of face presentation during
      first stage of labor.
AB  - We report an unusual case in which sonographic diagnosis of face presentation was
      made by translabial ultrasound examination during the first stage of labor. In a
      multigravida, induction of labor was performed at 39 weeks' gestation for
      suspected small-for-gestational age. The diagnosis of face presentation was
      confirmed by the use of intrapartum translabial ultrasound examination. In face
      presentation, the orbits and nasal bridge are shown in the center of the
      presenting part at the mid-sagittal plane. Emergency cesarean delivery was
      performed for labor dystocia. Here we discuss the merits and limitations of
      transabdominal, transvaginal and translabial ultrasound examinations in assisting
      clinical diagnosis of non-vertex malpresentation. We propose the use of
      intrapartum translabial scan in documentation, counseling and education in case
      of unusual non-vertex malpresentation.

PMID- 21955209
TI  - Generation of antibody-producing hybridomas following one single immunization
      with a targeted DNA vaccine.
AB  - The standard protocol for generating antibody (Ab)-producing hybridomas is based
      on fusion of plasmacytoma cells with Ab-producing B cells harvested from
      immunized mice. To increase the yield of hybridomas, it is important to use
      immunization protocols that induce a high frequency of B cells producing specific
      Abs. Our laboratory has developed a vaccine format, denoted vaccibody that
      promotes the immune responses towards the delivered antigen. The vaccine format
      targets antigens in a bivalent form to surface receptors on antigen-presenting
      cells (APCs). Here, we used the fluorescent protein (FP) mCherry as antigen and
      targeted it to APCs by use of either the natural ligand CCL3/MIP-1alpha or single
      chain variable fragment specific for major histocompatibility complex class II.
      The vaccine format was delivered to mouse muscle as DNA combined with
      electroporation. By this procedure, we developed two monoclonal Abs that can be
      utilized to detect the FC mCherry in various applications. The data suggest that
      the targeted DNA vaccine format can be utilized to enhance the number of Ab
      producing hybridomas and thereby be a tool to improve the B cell hybridoma
      technology.

PMID- 21955211
TI  - Complete oral rehabilitation of a postresection ameloblastoma patient: a clinical
      case report.
AB  - Conventional ameloblastomas are rare, benign, epithelial odontogenic tumors that
      tend to grow slowly in the mandible or maxilla, but are locally invasive and can
      be highly destructive of the surrounding dental anatomy. Aggressive resection is
      the most effective method of eliminating the tumors, but treatment can further
      contribute to patient deformity and malfunction. Ameloblastomas also have a high
      rate of recurrence, which significantly diminishes 8 years after resection, but
      still requires vigilant clinical monitoring. This case report describes the
      complete oral rehabilitation of a postresection ameloblastoma patient with a
      mandibular reconstruction plate and partial edentulism. An autogenous graft was
      taken from the patient's iliac crest, shaped to fit the defect, and attached with
      bone screws. After graft incorporation, dental implants were successfully placed
      into the augmented ridge and restored with a fixed partial denture. There was no
      evidence of tumor recurrence during the 10 months of treatment or 8 years of
      subsequent clinical monitoring.

PMID- 21955212
TI  - A critical review of the molecular pathophysiology of lenalidomide sensitivity in
      5q - myelodysplastic syndromes.
AB  - Abstract   The 5q deletion is a chromosomal abnormality that is observed in a
      subset of myelodysplastic syndromes (MDS). When isolated, this abnormality
      defines a specific clinical syndrome termed MDS associated with isolated deletion
      5q, presenting with macrocytic anemia, normal platelet count or slight
      thrombocytosis, hypolobated megakaryocytes and fewer than 5% blasts in the bone
      marrow. MDS with the 5q deletion have a particular sensitivity to treatment with
      lenalidomide, a thalidomide analog. In this article, molecular changes in 5q- MDS
      derived from haploinsufficiency of genes encoded from the deleted region in 5q
      are reviewed, and mechanisms that link these molecular lesions with lenalidomide
      sensitivity are proposed.

PMID- 21955213
TI  - Person-to-person transmission of severe fever with thrombocytopenia syndrome
      virus.
AB  - Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious
      disease caused by a newly discovered bunyavirus, SFTS virus (SFTSV), and causes
      high fatality (12% on average and as high as 30%). The objective of this study
      was to determine whether SFTSV could be transmitted from person to person. We
      analyzed sera of 13 patients from two clusters of unknown infectious diseases
      that occurred between September and November of 2006 in Anhui Province of China
      for SFTSV antibody by indirect immunofluorescence assay and for SFTSV RNA by RT
      PCR. We found that all patients (n=14) had typical clinical symptoms of SFTS
      including fever, thrombocytopenia, and leukopenia and all secondary patients in
      both clusters got sick at 6-13 days after contacting or exposing to blood of
      index patients. We demonstrated that all patients in cluster 1 including the
      index patient and nine secondary patients and all three secondary patients in
      cluster 2 had seroconversion or fourfold increases in antibody titer to SFTSV
      and/or by RT-PCR amplification of SFTSV RNA from the acute serum. The index
      patient in cluster 2 was not analyzed because of lack of serum. No person who
      contacted the index patient during the same period, but were not exposed to the
      index patient blood, had got illness. We concluded that SFTSV can be transmitted
      from person to person through contacting patient's blood.

PMID- 21955215
TI  - Ablation of perimitral flutter following catheter ablation of atrial
      fibrillation: impact on outcomes from a randomized study (PROPOSE).
AB  - INTRODUCTION: Patients with previous ablation for atrial fibrillation (AF) may
      experience recurrence of perimitral flutter (PMFL). These arrhythmias are usually
      triggered from sources that may also induce AF. This study aims at determining
      whether ablation of triggers or completing mitral valve isthmus (MVI) block
      prevents more arrhythmia recurrences. METHODS AND RESULTS: Sixty-five patients
      with recurrent PMFL after initial ablation of long standing persistent AF were
      included in this study. Thirty-two patients were randomized to MVI ablation only
      (Group 1) and 33 were randomized to cardioversion and repeat pulmonary vein (PV)
      isolation plus ablation of non-PV triggers (Group 2). MVI bidirectional block was
      achieved in all but 1 patient from Group 1. In Group 2, reconnection of 17 PVs
      was detected in 14 patients (42%). With isoproterenol challenge, 44 non-PV
      trigger sites were identified in 28 patients (85%, 1.57 sites per patient). At 18
      month follow-up, 27 patients (84%) from Group 1 had recurrent atrial
      tachyarrhythmias, of whom 15 remained on antiarrhythmic drug (AAD); however, 28
      patients from Group 2 (85%, P < 0.0001 vs Group 1) were free from arrhythmia off
      AAD. The ablation strategy used in Group 2 was associated with a lower risk of
      recurrence (hazard ratio = 0.10, 95% CI 0.04-0.28, P < 0.001) and an improved
      arrhythmia-free survival (log rank P < 0.0001). CONCLUSION: In patients
      presenting with PMFL after ablation for longstanding persistent AF, MVI block had
      limited impact on arrhythmia recurrence. On the other hand, elimination of all PV
      and non-PV triggers achieved higher freedom from atrial arrhythmias at follow-up.

PMID- 21955214
TI  - Tick cell lines for study of Crimean-Congo hemorrhagic fever virus and other
      arboviruses.
AB  - Continuous cell lines derived from many of the vectors of tick-borne arboviruses
      of medical and veterinary importance are now available. Their role as tools in
      arbovirus research to date is reviewed and their potential application in studies
      of tick cell responses to virus infection is explored, by comparison with recent
      progress in understanding mosquito immunity to arbovirus infection. A preliminary
      study of propagation of the human pathogen Crimean-Congo hemorrhagic fever virus
      (CCHFV) in tick cell lines is reported; CCHFV replicated in seven cell lines
      derived from the ticks Hyalomma anatolicum (a known vector), Amblyomma
      variegatum, Rhipicephalus (Boophilus) decoloratus, Rhipicephalus (Boophilus)
      microplus, and Ixodes ricinus, but not in three cell lines derived from
      Rhipicephalus appendiculatus and Ornithodoros moubata. This indicates that tick
      cell lines can be used to study growth of CCHFV in arthropod cells and that there
      may be species-specific restriction in permissive CCHFV infection at the cellular
      level.

PMID- 21955216
TI  - Ochroconis gallopava: a dematiaceous mold causing infections in transplant
      recipients.
AB  - The dematiaceous mold Ochroconis gallopava is increasingly recognized as a human
      pathogen. Infection is almost always associated with immunosuppression. We
      describe a case with a unique presentation in a kidney transplant recipient and
      retrospectively review all 10 cases of O. gallopava at our institution over 18
      yr, all in organ transplant recipients. Sixty percent of infections at our
      institution occurred in the last five yr studied. Infection generally occurred
      late after transplantation, and pulmonary infection was the most common
      manifestation. Use of almetuzumab for induction was associated with infection in
      the first six months post-transplant (p = 0.03). Attributable mortality at six
      months was 20%. Ochroconis gallopava is a rare but important pathogen in
      immunosuppressed individuals and organ transplantation is the most common
      underlying condition. Pulmonary involvement is the most common manifestation
      among patients with organ transplant. Optimal therapy remains undefined.
      Prognosis in organ transplant recipients is good if infection is diagnosed prior
      to dissemination.

PMID- 21955217
TI  - Automatic structure determination of regular polysaccharides based solely on NMR
      spectroscopy.
AB  - The structural analysis of polysaccharides requires that the sugar components and
      their absolute configurations are determined. We here show that this can be
      performed based on NMR spectroscopy by utilizing butanolysis with (+)- and (-)-2
      butanol that gives the corresponding 2-butyl glycosides with characteristic (1)H
      and (13)C NMR chemical shifts. The subsequent computer-assisted structural
      determination by CASPER can then be based solely on NMR data in a fully automatic
      way as shown and implemented herein. The method is additionally advantageous in
      that reference data only have to be prepared once and from a user's point of view
      only the unknown sample has to be derivatized for use in CASPER.

PMID- 21955218
TI  - Thrombin generation in type 2 diabetes with albuminuria and macrovascular
      disease.
AB  - BACKGROUND: Albuminuria is an indicator of cardiovascular morbidity and mortality
      in patients with type 2 diabetic mellitus (T2DM). MATERIALS AND METHODS: In our
      cross-sectional study, we measured thrombin generation (TG), a key process in
      haemostasis and a tool to detect an individual's coagulation potential, in normo
      , micro- and macroalbuminuria in T2DM with and without macrovascular disease
      (MVD). The TG-assay was performed, and the TG-curve [including the lag phase,
      peak thrombin and area under the curve (AUC)] was analysed. RESULTS: A total of
      160 patients (62 women; mean age +/- SD: 67 +/- 11 years) with T2DM and normo-,
      micro- or macroalbuminuria were investigated. Of those, 90 (56%) patients had
      normoalbuminuria, 40 (25%) microalbuminuria and 30 (19%) macroalbuminuria. The
      AUC between the groups of patients with normo-, micro- and macroalbuminuria was
      statistically significantly different [3297 (2785; 3764) vs. 3222 (2381; 3678)
      vs. 3726 (3153; 4235) nM Thrombin; P = 0AE019]. T2DM patients with MVD (n = 121)
      had a significantly shorter lag phase [12 (9; 16) vs. 20 (15; 25) min; P <
      0AE001], a significantly higher peak thrombin [233 (130; 339) vs. 133 (82; 187)
      nM; P < 0AE001] and a significantly higher AUC [3464 (2969; 3868) vs. 3091 (2384;
      3619) nM Thrombin; P = 0AE01] than T2DM patients without MVD (n = 39), indicating
      an earlier and higher thrombin generation. CONCLUSION: Our results support the
      hypothesis that TG may be involved in the pathogenesis of MVD in diabetic
      nephropathy as for the first time, we could show that patients with T2DM in
      different stages of diabetic nephropathy had disturbances in thrombin generation.

PMID- 21955219
TI  - Stability of therapeutic albumin solutions used for molecular adsorbent
      recirculating system-based liver dialysis.
AB  - Mounting evidence suggests beneficial effects of albumin dialysis-based liver
      support in patients suffering from acute-on-chronic liver failure. Molecular
      adsorbent recirculating system (MARS) is a nonbiological liver support device,
      based on the exchange of albumin-bound toxins between the patient's blood and a
      20% human serum albumin solution in a secondary circuit. Bound toxins are
      continuously removed from the circulating albumin by exposure to activated
      charcoal and an ion-exchange resin. The aim of the present in vitro study was to
      determine the impact of exposure to charcoal and resin on the ligand binding
      properties of albumins, containing various levels of stabilizers and obtained
      from different suppliers (Baxter, CAF-DCF [Red Cross], and Sigma-Aldrich).
      Albumin binding properties were assessed by measuring equilibrium binding
      properties of warfarin, diazepam, and salicylate before and after incubation (for
      up to 7 h) with adsorbing materials; albumin-associated esterase-like activities
      were also determined. Notable changes in albumin binding upon incubation with
      adsorbing materials were only observed when using warfarin as a ligand. Affinity
      of warfarin for the Baxter and Sigma albumins showed a pronounced decrease
      (higher K(d) ) after the 1-7-h exposure to charcoal or resin. In the absence of
      adsorbing materials, similar effects were found, indicating that incubation time
      per se affects albumin binding properties. Following exposure to resin, Baxter
      albumin binding capacity (B(max)) increased about twofold. For albumin obtained
      from CAF-DCF, binding affinity and capacity for warfarin were constant under all
      conditions tested. Esterase-like activities associated with these albumins were
      either maintained or enhanced (up to 2.5-fold in case of Sigma albumin) following
      7-h incubations with adsorbing materials. Our data suggest limited direct
      influence of the presence of stabilizers in therapeutic albumin solutions on
      baseline binding properties of human albumin. However, in vitro incubations of
      these albumins for several hours resulted in supplier-specific changes in
      warfarin binding, suggesting an influence of stabilizers on the stability of
      binding properties. Further preclinical and clinical studies are required to
      elucidate the clinical relevance of these in vitro results, that is, to what
      extent these changes in albumin binding properties result in altered performance
      of albumins in the secondary circuit during the MARS procedure.

PMID- 21955220
TI  - Predictors of slow-wave sleep in a clinic-based sample.
AB  - Slow-wave sleep has been associated with several physiological phenomena,
      including glucose metabolism, sympathetic nervous system activity, hormonal
      secretion and blood pressure regulation. The aim of these analyses was to
      determine which sociodemographic and medical factors were associated with slow
      wave sleep duration in a large clinical sample. We conducted cross-sectional
      analysis of clinical data from 1019 consecutive adults over a 10-month period who
      had their first in-laboratory polysomnogram for suspicion of obstructive sleep
      apnea. Patients either underwent in-laboratory full-night polysomnogram followed
      by full-night continuous positive airway pressure titration or split-night
      polysomnogram. Patients also completed questionnaires to assess race, education,
      marital status and medical co-morbidities. A multiple linear regression model
      that predicted the natural log of slow-wave sleep in minutes indicated that
      African Americans had approximately 48% less slow-wave sleep than non-African
      Americans. Increasing age and male gender were also associated with less slow
      wave sleep. Overweight and obese individuals had significantly less slow-wave
      sleep than those not overweight, even after adjustment for obstructive sleep
      apnea severity. Finally, those with severe obstructive sleep apnea had
      significantly less slow-wave sleep than those with less severe obstructive sleep
      apnea even after adjustment for obesity. Results remained unchanged when patients
      who had a split-night polysomnogram were excluded. We observed less slow-wave
      sleep in African Americans, a group at increased risk of diabetes and
      hypertension compared with Caucasians, and in those who are overweight and obese
      and those with severe obstructive sleep apnea. Future research needs to explore
      potential reasons for reduced slow-wave sleep in these individuals.

PMID- 21955221
TI  - Quantifying the effects of 1,1,1-trichloroethane and 1,1-dichloroethane on
      chlorinated ethene reductive dehalogenases.
AB  - Mixtures of chlorinated ethenes and ethanes are often found at contaminated
      sites. In this study, we undertook a systematic investigation of the inhibitory
      effects of 1,1,1-trichloroethane (1,1,1-TCA) and 1,1-dichloroethane (1,1-DCA) on
      chlorinated ethene dechlorination in three distinct Dehalococcoides-containing
      consortia. To focus on inhibition acting directly on the reductive dehalogenases,
      dechlorination assays used cell-free extracts prepared from cultures actively
      dechlorinating trichloroethene (TCE) to ethene. The dechlorination assays were
      initiated with TCE, cis-1,2-dichloroethene (cDCE), or vinyl chloride (VC) as
      substrates and either 1,1,1-TCA or 1,1-DCA as potential inhibitors. 1,1,1-TCA
      inhibited VC dechlorination similarly in cell suspension and cell-free extract
      assays, implicating an effect on the VC reductases associated with the
      dechlorination of VC to nontoxic ethene. Concentrations of 1,1,1-TCA in the range
      of 30-270 MUg/L reduced VC dechlorination rates by approximately 50% relative to
      conditions without 1,1,1-TCA. 1,1,1-TCA also inhibited reductive dehalogenases
      involved in TCE and cDCE dechlorination. In contrast, 1,1-DCA had no pronounced
      inhibitory effects on chlorinated ethene reductive dehalogenases, indicating that
      removal of 1,1,1-TCA via reductive dechlorination to 1,1-DCA is a viable strategy
      to relieve inhibition.

PMID- 21955222
TI  - Allergenic activity of different tomato cultivars in tomato allergic subjects.
AB  - BACKGROUND: Tomatoes (Solanum lycopersicum) are consumed worldwide and their
      amount of consumption is associated with the prevalence of tomato allergy.
      Therefore, identification of tomato cultivars with reduced allergenicity would
      potentially increase the quality of life of affected subjects. OBJECTIVE: In this
      study, we examined the allergenic and biological activity of two different tomato
      cultivars in tomato allergic subjects. METHODS: Twenty-five subjects with tomato
      allergy were identified using double-blind, placebo-controlled food challenges
      (DBPCFC). We applied skin prick test (SPT) and further DBPCFC to investigate the
      clinical differences between two tomato cultivars ('Reisetomate' and 'Matina').
      To examine the molecular basis of allergenic activity, immunoblotting and
      basophil activation test (BAT) were performed. RESULTS: The cultivar
      'Reisetomate' induced significantly less positive skin reactions (P = 0.045) and
      elicited fewer symptoms after oral challenge compared with 'Matina' (P = 0.047).
      Molecular assessment revealed that IgE-binding profiles were variable on an
      interindividual basis, but no major differences between 'Reisetomate' and
      'Matina' were detectable. In contrast, BAT underpinned the clinical differences
      evoked by the different tomato cultivars and showed a left-shift of the dose
      response curve obtained for 'Matina' extract (P = 0.046). CONCLUSIONS AND
      CLINICAL RELEVANCE: Tomato cultivars promote a distinct clinical reactivity in
      tomato allergic subjects, demonstrated using SPT, DBPCFC and BAT. The molecular
      background for these differences could not be clarified, as the IgE-binding
      profiles did not reveal significant alterations. This might be due to
      instabilities of physicochemical sensitive proteins and/or different isoform
      expression of allergens.

PMID- 21955223
TI  - Profile of vitiligo patients attending a training and research hospital in
      Central Anatolia: a retrospective study.
AB  - Clinical characteristics of vitiligo had been reported in different countries
      previously. This is the second report from Turkey and it is from a different
      region of Turkey, middle Anatolia, and a more detailed study. The age and sex of
      patients, onset age, duration, areas of involvement, course, clinical types and
      severity of the disease, family history of vitiligo, associated disorders, the
      values of vitamin B12, folic acid, ferritin, iron and hemoglobin,
      antithyroglobulin and antithyroid peroxidase antibodies and positivity of viral
      markers were obtained from the records of the patients retrospectively. The study
      involved 93 vitiligo patients with a mean age of 37.4+/-17.05 years. The median
      age of onset disease was 33 years and onset age of disease was significantly
      lower in women. Of the patients, 24.8% had family history. The most frequent form
      of vitiligo was vitiligo vulgaris. Facial involvement was the most common
      localization. Trunk involvement was significantly higher in women but anogenital
      involvement was significantly higher in men. Of the patients, 40.3% had another
      autoimmune disease, 19.7% of the patients had low ferritin levels, 12% had low
      iron levels, 9.9% had anemia, 4.9% had low vitamin B12 levels, 3.8% had low folic
      acid levels and 4.3% had positivity of viral markers. The age of onset and the
      incidence of family history were higher and sites of involvement according to sex
      were different from the published work. The knowledge of clinical
      characteristics, course and associated conditions of vitiligo may improve the
      approach of dermatologists to vitiligo patients.

PMID- 21955224
TI  - Diazepam promotes choice of abstinence in cocaine self-administering rats.
AB  - When facing a choice between cocaine and a potent, albeit inessential, non-drug
      alternative (i.e. water sweetened with saccharin), most cocaine self
      administering rats abstain from cocaine in favor of the non-drug pursuit,
      regardless of the dose available and even after extended drug use. Only a
      minority continues to take the drug despite the opportunity of making a different
      choice and increasing stakes. This pattern of individual variation could suggest
      that the majority of rats are resilient to addiction, taking cocaine by default
      of other options. Only a minority would be vulnerable to addiction. This study
      tested the hypothesis that rats choose to refrain from cocaine self
      administration because cocaine would be conflictual, having both rewarding and
      anxiogenic properties. Contrary to this hypothesis, however, we report here that
      diazepam-a broad-spectrum benzodiazepine anxiolytic-did not decrease, but
      instead, further increased cocaine abstinence. Interestingly, although diazepam
      decreased locomotion, rats adapted to this effect by spending more time near the
      lever associated with the preferred reward, a behavior that minimized the need
      for locomotion at the moment of choice. When responding for cocaine or saccharin
      was analyzed separately, we found that diazepam decreased responding for cocaine
      without affecting responding for saccharin. Finally, the abstinence-promoting
      effects of diazepam were also induced in cocaine-preferring rats treated
      chronically with diazepam. Overall, this study demonstrates that abstinence from
      cocaine cannot be explained away by the anxiogenic effects of cocaine, thereby
      reinforcing the notion of resilience to addiction. It also supports the use of
      benzodiazepines in the treatment of cocaine addiction.

PMID- 21955226
TI  - Environmental effects on the detection of adaptation.
AB  - Detecting adaptation involves comparing the performance of populations evolving
      in different environments. This detection may be confounded by effects due to the
      environment experienced by organisms prior to the test. We tested whether such
      confounding effects occur, using spider-mite selection lines on two novel hosts
      and one ancestral host, after 15 generations of selection. Mites were either
      sampled directly from the selection lines or subjected to a common juvenile or to
      a common maternal environment, mimicking the most frequent environmental
      manipulations. These environments strongly affected all life-history traits.
      Moreover, the detection of adaptation and correlated responses on the ancestral
      host was inconsistent among environments in almost 20% of the cases. Indeed, we
      did not detect responses unambiguously for any life-history trait. This
      inconsistency was due to differential environmental effects on lines from
      different selection regimes. Therefore, the detection of adaptation requires a
      careful control of these environmental effects.

PMID- 21955227
TI  - Why are the elderly so susceptible to pneumonia?

PMID- 21955228
TI  - Measuring the benefits of school closure interventions to mitigate influenza.

PMID- 21955225
TI  - Switching patients with uncontrolled hypertension on amlodipine 10 mg to single
      pill combinations of telmisartan and amlodipine: results of the TEAMSTA-10 study.
AB  - OBJECTIVE: To evaluate the efficacy and safety of two different strengths of
      single-pill combinations of the angiotensin II receptor blocker telmisartan 40 or
      80 mg (T40 or T80) and the calcium channel blocker amlodipine 10 mg (A10)
      compared with that of A10 monotherapy in a hypertensive patient population whose
      blood pressure was not controlled by A10. RESEARCH DESIGN AND METHODS: An 8-week,
      randomized, double-blind, controlled study to compare the efficacy and safety of
      single-pill combinations of T40/A10 or T80/A10 versus A10 monotherapy in 947
      patients with uncontrolled hypertension (diastolic blood pressure [DBP] >=90 mmHg
      after 6 weeks' A10). MAIN OUTCOME MEASURES: The primary end point was change from
      baseline in seated in-clinic trough cuff DBP after 8 weeks. Secondary efficacy
      end points included change from baseline in seated in-clinic trough cuff systolic
      blood pressure (SBP), and the proportion of patients achieving SBP/DBP response
      (<140/90 mmHg or >=10/15 mmHg reduction) and SBP/DBP goal (<140/90 mmHg) after 8
      weeks' treatment. Adverse events were recorded throughout. RESULTS: In a patient
      population who had failed to achieve DBP goal with A10, T40/A10 and T80/A10
      resulted in significantly greater (P < 0.0001) reductions in seated trough
      SBP/DBP versus A10 (-3.7/-2.8 mmHg; -3.9/-2.8 mmHg), significantly higher SBP/DBP
      goal rates versus A10 (58.8/63.7% and 60.3/66.5% vs. 50.2/51.1%), and
      significantly higher SBP/DBP response rates with T40-80/A10 versus A10
      (64.7/66.0% and 65.8/68.7% vs. 54.1/53.4%). T40-80/A10 were well tolerated. Rates
      of peripheral edema adverse events were low (6.7-8.5%) and not significantly
      different between the treatment groups; however, patients were pre-screened for
      intolerance to A10. CONCLUSIONS: Switching patients who fail to achieve blood
      pressure goal with A10 to a single-pill combination of T40/A10 or T80/A10 results
      in superior SBP/DBP reductions, and SBP/DBP goal and response rates.

PMID- 21955229
TI  - Symptoms or severity: what to act upon?

PMID- 21955232
TI  - Inhibiting or blocking LIGHT, a TNF superfamily member, for treating airway
      remodeling.

PMID- 21955231
TI  - Tobramycin Inhalation PowderTM: a novel drug delivery system for treating chronic
      Pseudomonas aeruginosa infection in cystic fibrosis.
AB  - Lung disease in cystic fibrosis (CF) is typified by the development of chronic
      airways infection culminating in bronchiectasis and progression to end-stage
      respiratory disease. Pseudomonas aeruginosa, a ubiquitous gram-negative bacteria,
      is the archetypical CF pathogen and is associated with an accelerated clinical
      decline. The development and widespread use of chronic suppressive aerosolized
      antibacterial therapies, in particular Tobramycin Inhalation Solution (TIS), in
      CF has contributed to reduced lung function decline and improved survival.
      However, the requirement for the aerosolization of these agents through
      nebulizers has been associated with increased treatment burden, reduced quality
      of life and remain a barrier to broader uptake. Tobramycin Inhalation Powder
      (TIPTM) has been developed by Novartis with the express purpose of delivering the
      same benefits as TIS in a time-effective manner. Administered via the T-326TM
      (Novartis) Inhaler in four individual 28-mg capsules, TIP can be administered in
      a quarter of the time of traditional nebulizers and is inherently portable. In
      clinical studies, TIP has been shown to be safe, result in equivalent or superior
      reductions in P. aeruginosa sputum density and produce similar improvements in
      pulmonary function. TIP offers significant advantages in time saving, portability
      and convenience over traditional nebulized TIS with comparable clinical outcomes
      for individuals with CF.

PMID- 21955233
TI  - Use of extracorporeal life support in adults with severe acute respiratory
      failure.
AB  - Extracorporeal membrane oxygenation (ECMO) is a recognized and accepted
      therapeutic option in the treatment of neonatal and pediatric respiratory
      failure. However, early studies in adults did not demonstrate a survival benefit
      associated with the utilization of ECMO for severe acute respiratory failure.
      Despite this historical lack of benefit, use of ECMO in adult patients has seen a
      recent resurgence. Local successes and a recently published randomized trial have
      both demonstrated promising results in an adult population with high baseline
      mortality and limited therapeutic options. This article will review the history
      of ECMO use for respiratory failure; investigate the driving forces behind the
      latest surge in interest in ECMO for adults with refractory severe acute
      respiratory failure; and describe potential applications of ECMO that will likely
      increase in the near future.

PMID- 21955235
TI  - Extrapulmonary comorbidities in chronic obstructive pulmonary disease: state of
      the art.
AB  - Extrapulmonary comorbidities are common and significant in chronic obstructive
      pulmonary disease (COPD), often contributing to symptoms, exacerbations, hospital
      admissions and mortality. Cardiovascular, musculoskeletal and psychological
      conditions are among the most prevalent and important of these. In particular,
      ischemic heart disease is a leading cause of death in the COPD population as a
      whole. Here, we provide a state-of-the-art summary of key comorbidities observed
      in COPD patients in terms of their prevalence, impact, pathophysiology and
      prognosis. In addition, we review clinical, diagnostic and management strategies
      that may differ in COPD patients from the rest of the population.

PMID- 21955234
TI  - Asthma morbidity and treatment in children with sickle cell disease.
AB  - Children with sickle cell disease (SCD) and a comorbid condition of asthma have
      increased numbers of vaso-occlusive pain and acute chest syndrome episodes, and
      all-cause mortality. When assessed systematically, asthma prevalence is probably
      similar among children with SCD when compared with the general African-American
      population. With increasing recognition of the importance of asthma in the
      management of SCD, hematologists must become familiar with asthma and develop a
      multidisciplinary approach, including early recognition, appropriate management
      and referral to asthma specialists.

PMID- 21955236
TI  - Ventilator-associated pneumonia in burn patients: a cause or consequence of
      critical illness?
AB  - Infectious complications are a constant threat to thermally injured patients
      during hospitalizations and are a predominant cause of death. Most of the
      infections that develop in burn patients are nosocomial and of a pulmonary
      etiology. The bacteria that cause ventilator associated pneumonia (VAP) take
      advantage of the fact that uniquely among intensive care unit patients
      endotracheal intubation allows them a 'free' passage to the sterile lower
      airways; however, the combination of severe thermal injury (systemic
      immunosuppression) and inhalation injury (local immunosuppression and tissue
      injury) create an ideal environment for development of VAP. Thus, strategies
      directed at preventing and treating VAP in burn patients must address not only
      rapid extubation and VAP prevention bundles known to work in other intensive care
      unit populations, but therapies directed to more rapid wound healing and
      restoration of pulmonary patency.

PMID- 21955237
TI  - Schistosomiasis and pulmonary hypertension.
AB  - Schistosomiasis is one of the most prevalent chronic infectious diseases in the
      world. One of its most severe complications, pulmonary hypertension, occurs in up
      to 5% of patients with hepatosplenic schistosomiasis. The prevalence of
      schistosomiasis is so overwhelming that schistosomiasis-associated pulmonary
      hypertension (Sch-PH) may be the most prevalent cause of pulmonary hypertension
      around the world. Multiple pathways have been described as potential mechanisms
      of disease in Sch-PH, such as egg embolism, inflammatory disease or pulmonary
      blood overflow. The possible physiopathological mechanisms will be discussed in
      this article, as well the disease's clinical course and response to the treatment
      available.

PMID- 21955239
TI  - miRNA expression and its clinical implications for the prevention and diagnosis
      of non-small-cell lung cancer.
AB  - miRNAs are a recently discovered category of small noncoding RNAs that regulate
      gene expression at the post-transcriptional level. Altered expressions of miRNAs
      are reported in a variety of human cancers and may associate with cancer
      pathogenesis, apoptosis and cell growth, thereby functioning as either oncogenes
      or tumor suppressors. Accumulating evidence indicates that deregulation of miRNA
      contributes to tumor initiation and progression and hence, has clinical value in
      several human cancers, including non-small-cell lung cancer. This article
      discusses the current knowledge of miRNAs in risk assessment, prevention, early
      diagnosis, prognosis and their possible role as oncogenes or tumor suppressors in
      the pathogenesis of non-small-cell lung cancer.

PMID- 21955238
TI  - Simian virus 40 transformation, malignant mesothelioma and brain tumors.
AB  - Simian virus 40 (SV40) is a DNA virus isolated in 1960 from contaminated polio
      vaccines, that induces mesotheliomas, lymphomas, brain and bone tumors, and
      sarcomas, including osteosarcomas, in hamsters. These same tumor types have been
      found to contain SV40 DNA and proteins in humans. Mesotheliomas and brain tumors
      are the two tumor types that have been most consistently associated with SV40,
      and the range of positivity has varied about from 6 to 60%, although a few
      reported 100% of positivity and a few reported 0%. It appears unlikely that SV40
      infection alone is sufficient to cause human malignancy, as we did not observe an
      epidemic of cancers following the administration of SV40-contaminated vaccines.
      However, it seems possible that SV40 may act as a cofactor in the pathogenesis of
      some tumors. In vitro and animal experiments showing cocarcinogenicity between
      SV40 and asbestos support this hypothesis.

PMID- 21955240
TI  - Recent advances in optical coherence tomography for the diagnoses of lung
      disorders.
AB  - There have been many advances in the field of diagnostic and therapeutic
      pulmonary medicine in the past several years, with major progress in the field of
      imaging. Optical coherence tomography (OCT) is a high-resolution (micron level)
      imaging modality currently being advanced with the potential to image airway wall
      structures in real time and at higher resolution than previously possible. OCT
      has the potential to increase the sensitivity and specificity of biopsies, create
      3D images of the airway to guide diagnostics, and may have a future role in
      diverse areas such as the evaluation and treatment of patients with obstructive
      sleep apnea, tracheal stenosis, airway remodeling and inhalation injury. OCT has
      recently been investigated to monitor airway compliance in chronic obstructive
      pulmonary disease and asthma patients as well as differentiate causes of
      pulmonary hypertension. In future clinical and research applications, OCT will
      likely be combined with other endoscopic based modalities such as ultrasound,
      spectroscopy, confocal, and/or photoacoustic tomography to determine functional
      and biomolecular properties. This article discusses the current uses of OCT, its
      potential applications, as it relates to specific pulmonary diseases, and the
      future directions for OCT.

PMID- 21955241
TI  - Hydrogen exchange study on the hydroxyl groups of serine and threonine residues
      in proteins and structure refinement using NOE restraints with polar side-chain
      groups.
AB  - We recently developed new NMR methods for monitoring the hydrogen exchange rates
      of tyrosine hydroxyl (Tyr-OH) and cysteine sulfhydryl (Cys-SH) groups in
      proteins. These methods facilitate the identification of slowly exchanging polar
      side-chain protons in proteins, which serve as sources of NOE restraints for
      protein structure refinement. Here, we have extended the methods for monitoring
      the hydrogen exchange rates of the OH groups of serine (Ser) and threonine (Thr)
      residues in an 18.2 kDa protein, EPPIb, and thus demonstrated the usefulness of
      NOE restraints with slowly exchanging OH protons for refining the protein
      structure. The slowly exchanging Ser/Thr-OH groups were readily identified by
      monitoring the (13)C(beta)-NMR signals in an H(2)O/D(2)O (1:1) mixture, for the
      protein containing Ser/Thr residues with (13)C, (2)H-double labels at their beta
      carbons. Under these circumstances, the OH groups exist in equilibrium between
      the protonated and deuterated isotopomers, and the (13)C(beta) peaks of the two
      species are resolved when their exchange rate is slower than the time scale of
      the isotope shift effect. In the case of EPPIb dissolved in 50 mM sodium
      phosphate buffer (pH 7.5) at 40  degrees C, one Ser and four Thr residues were
      found to have slowly exchanging hydroxyl groups (k(ex) < ~40 s(-1)). With the
      information for the slowly exchanging Ser/Thr-OH groups in hand, we could collect
      additional NOE restraints for EPPIb, thereby making a unique and important
      contribution toward defining the spatial positions of the OH protons, and thus
      the hydrogen-bonding acceptor atoms.

PMID- 21955242
TI  - Modulation of mouse gastrointestinal motility by allyl isothiocyanate, a
      constituent of cruciferous vegetables (Brassicaceae): evidence for TRPA1
      independent effects.
AB  - BACKGROUND AND PURPOSE: Allyl isothiocyanate (AITC, mustard oil), a constituent
      of many common cruciferous vegetables (Brassicaceae), activates transient
      receptor potential of ankyrin type-1 (TRPA1) channels, claimed to regulate
      gastrointestinal contractility. In this study, we have investigated the effect of
      AITC on intestinal motility. EXPERIMENTAL APPROACH: Effects of AITC were
      investigated in vivo on upper gastrointestinal transit in mice and in mouse
      isolated ileum [contractions induced by electrical field stimulation (EFS),
      acetylcholine and spontaneous contractility]. The contractor activity of AITC was
      studied in mouse isolated colon. The ability of TRPA1 channel antagonists to
      block AITC-induced elevation of intracellular Ca(2+) [Ca(2+)](i) was assessed in
      HEK293 cells transfected with rat TRPA1 channels. KEY RESULTS: AITC increased
      [Ca(2+)](i) in HEK293 cells, reduced ileal contractility (acetylcholine-, EFS
      induced contractions and spontaneous contractility), but contracted the isolated
      colon. Gentamicin and camphor (non-selective TRPA1 channel antagonists), HC
      030031 and AP18 (selective TRPA1 channel agonists) inhibited AITC-induced effects
      in HEK293 cells but not in the ileum or colon. AITC-induced contractions were
      reduced by tetrodotoxin and strongly reduced by nifedipine, cyclopiazonic acid
      and ryanodine. In vivo, AITC reduced (following i.p. administration) or increased
      (following intragastric administration) upper gastrointestinal transit in mice
      These effects were not affected by HC-030031. CONCLUSION AND IMPLICATIONS: AITC,
      depending, in vitro, on the regions of gut examined and, in vivo, on the route of
      administration, exerted both stimulatory and inhibitory effects on intestinal
      motility, which were not sensitive to TRPA1 channel antagonists. The proposition
      that TRPA1 channels are the primary targets for AITC to induce contraction should
      be revised.

PMID- 21955243
TI  - Dofetilide reduces the frequency of ventricular arrhythmias and implantable
      cardioverter defibrillator therapies.
AB  - BACKGROUND: Patients with an implanted cardioverter defibrillator (ICD) and
      ventricular arrhythmias leading to ICD therapies have poor clinical outcomes and
      quality of life. Antiarrhythmic agents and catheter ablation are needed to
      control these arrhythmias. Dofetilide has only been approved for the treatment of
      atrial fibrillation. The role of dofetilide in the control of ventricular
      arrhythmias in patients with an ICD has not been established. OBJECTIVE: Evaluate
      the safety and efficacy of dofetilide in a consecutive group of patients with an
      ICD and recurrent ventricular tachycardia (VT) and/ or ventricular fibrillation
      (VF) after other antiarrhythmic drugs have failed to suppress these arrhythmias.
      METHODS: We studied 30 patients (age 59 +/- 11; 5 women) with symptomatic VT or
      VF and ICDs for secondary prevention of sudden cardiac death. These patients had
      an average of 1.8 +/- 4.5 episodes of VT/VF per month despite antiarrhymic
      therapy. Twenty-one patients (70%) had recurrent appropriate ICD therapies prior
      to initiation of dofetilide, and 9 (30%) VTs below the programmed detection rate
      of the ICD. Twenty-three patients (77%) had coronary artery disease. Mean
      ejection fraction was 30 +/- 14% and 26/30 (87%) had congestive heart failure.
      All patients had previously failed 2 +/- 1 antiarrhythmic drugs including
      amiodarone (n = 19) and sotalol (n = 10). RESULTS: During the first month of
      treatment, 25 patients (83%) had complete suppression of VT/VF and of the 21
      patients with ICD therapies 16 (76%) had no therapies during the first month of
      treatment. During a follow-up period of 32 +/- 32 months, dofetilide reduced the
      monthly episodes of VT/VF from 1.8 +/- 4.5 to 1.0 +/- 3.5 (P = 0.006). Monthly
      ICD therapies decreased from 0.9 +/- 1.4 to 0.4 +/- 1.7 (P = 0.037). In 9
      patients that presented with slow VTs under the ICD detection zone, dofetilide
      reduced monthly VT/VF episodes from 0.7 +/- 0.6 to 0.1 +/- 0.1 (P = 0.01) and 6
      (67%) had no further ICD therapies. Dofetilide was discontinued in 13 patients
      (43%) after 24 +/- 30 months due to failure to control VT/VF (n = 7), placement
      of a left ventricular assist device (n = 3), catheter ablation (n = 1), heart
      transplantation (n = 1), and left ventricular restoration surgery (n = 1). There
      were 7 documented deaths (2 patients died suddenly; 3 patients of progressive
      heart failure; and 2 of non-cardiac causes). CONCLUSIONS: In patients with an ICD
      and ventricular arrhythmias, dofetilide decreases the frequency of VT/VF and ICD
      therapies even when other antiarrhythmic agents, including amiodarone, have
      previously been ineffective. Recurrences still occur in some patients requiring
      catheter ablation, mechanical support, or heart transplantation.

PMID- 21955244
TI  - Optimization of propafenone analogues as antimalarial leads.
AB  - Propafenone, a class Ic antiarrythmic drug, inhibits growth of cultured 
      Plasmodium falciparum.  While the drug's potency is significant, further
      development of propafenone as an antimalarial would require divorcing the
      antimalarial and cardiac activities as well as improving the pharmacokinetic
      profile of the drug. A small array of propafenone analogues was designed and
      synthesized to address the cardiac ion channel and PK liabilities. Testing of
      this array revealed potent inhibitors of the 3D7 (drug sensitive) and K1 (drug
      resistant) strains of P. falciparum that possessed significantly reduced ion
      channel effects and improved metabolic stability. Propafenone analogues are
      unusual among antimalarial leads in that they are more potent against the
      multidrug resistant K1 strain of P. falciparum compared to the 3D7 strain.

PMID- 21955245
TI  - Characterization and comparison of 'standard' and 'young' tumour-infiltrating
      lymphocytes for adoptive cell therapy at a Danish translational research
      institution.
AB  - Adoptive cell therapy (ACT) with ex vivo expanded tumour-infiltrating lymphocytes
      (TILs) in combination with IL-2 is an effective treatment for metastatic
      melanoma. Modified protocols of cell expansion may allow the treatment of most
      enrolled patients and improve the efficacy of adoptively transferred cells. The
      aims of this study were to establish and validate the novel 'Young TIL' method at
      our institution and perform a head-to-head comparison of clinical-grade products
      generated with this protocol opposed to the conventional 'Standard TIL', which we
      are currently using in a pilot ACT trial for patients with melanoma. Our results
      confirm that 'Young TILs' display an earlier differentiation state, with higher
      CD27 and lower CD56 expression. In addition, CD8(+) TILs expressing CD27 had
      longer telomeres compared with the CD27(-). A recently described subset of NK
      cells, endowed with a high expression of CD56 (CD56(bright)), was detected for
      the first time in both types of cultures but at a higher frequency on Young TILs.
      Young and Standard TILs' reactivity against autologous tumours was similar, with
      significant expression of TNF-alpha/IFN-gamma/CD107a by CD8(+) TILs detected in
      all cultures analysed. However, either slow expansion with high-dose IL-2 only or
      large numerical expansion with a rapid expansion protocol, which is required for
      current therapeutic protocols, significantly modified TIL phenotype by reducing
      the frequency of less differentiated, cancer-specific TILs. These studies further
      support the adoption of the Young TIL method in our current ACT trial and
      highlight the importance of continuous quality control of expansion protocols.

PMID- 21955246
TI  - Annexin A2 in amniotic fluid: correlation with histological chorioamnionitis,
      preterm premature rupture of membranes, and subsequent preterm delivery.
AB  - AIM: The aim of this study was to determine whether amniotic fluid levels of
      annexin A2, a phospholipid-binding protein that is abundant in amnion and
      regulates fibrin homeostasis, are associated with histological chorioamnionitis,
      preterm premature rupture of the membranes, and subsequent preterm delivery.
      MATERIALS AND METHODS: Amniotic fluid was obtained from 55 pregnant women with
      preterm labor and/or preterm premature rupture of the membranes before 32weeks of
      gestation, and amniotic fluid levels of annexin A2 were measured with a sandwich
      enzyme-linked immunosorbent assay. RESULTS: Amniotic fluid levels of annexin A2
      in patients with histological chorioamnionitis was higher than that in the
      remainder (P=0.053), whereas amniotic fluid levels of annexin A2 in patients with
      preterm premature rupture of the membranes was significantly higher than that in
      the remainder (P=0.002). Amniotic levels of annexin A2 was a fair test (area
      under receiver-operator characteristic curve=0.679), and amniotic fluid levels of
      annexin A2>878.2ng/mL had a sensitivity of 68.8%, a specificity of 65.2%, a
      positive predictive value of 73.3%, and a negative predictive value of 60.0% for
      predicting delivery within 2weeks after amniotic fluid sampling. Furthermore, the
      combined use of amniotic fluid cut-off levels of 878.2ng/mL for annexin A2 and
      13.3ng/mL for interleukin-8 improved the specificity (91.3%) and the positive
      predictive value (89.5%). CONCLUSIONS: We identified amniotic fluid levels of
      annexin A2, especially in combination with amniotic fluid levels of interleukin
      8, as a novel predictive marker for preterm delivery.

PMID- 21955247
TI  - Could exhaled ferritin and SOD be used as markers for lung cancer and prognosis
      prediction purposes?
AB  - BACKGROUND: Today an increasing interest is being generated by the study of lung
      cancer markers in the exhaled breath condensate (EBC), precisely because this
      sample seems to lend itself to lung cancer early screening and follow-up. Indeed,
      ferritin and superoxide dismutase (SOD) have recently been recognized to play a
      role in lung cancerogenesis and patients' survival. The aim of this study was to
      evaluate the clinical value and the prognostic power of exhaled ferritin and
      exhaled SOD in patients with lung cancer. MATERIAL AND METHODS: Forty patients
      with nonsmall cell lung cancer (NSCLC) and 15 controls were enrolled in the
      study. All subjects under study underwent EBC collection and analysis of ferritin
      and SOD. A total of 36 patients were either given a follow-up of at least 25.5
      months or followed up until death. RESULTS: Exhaled ferritin and SOD resulted as
      being higher in NSCLC than in controls and as being influenced by the stage of
      cancer. A pronounced survival difference was found in the presence of exhaled
      ferritin 300 ng/mL and exhaled SOD > 13.5 U/MUL. CONCLUSIONS: In conclusion,
      although the results need to be confirmed on a larger and homogeneous population,
      we hypothesized that the notion of using the measurement of ferritin and SOD in
      the EBC could, if deemed feasible, have clinical implications in the monitoring
      of lung cancer and as an outcome predictor.

PMID- 21955248
TI  - Helminth community composition, structure, and pattern in six dove species
      (Columbiformes: Columbidae) of South Texas.
AB  - The helminth community composition and structure of 6 species of columbids
      residing in south Texas are reported and compared herein. Sixty individuals of
      the following species, rock pigeons (Columba livia [RP]), mourning doves (Zenaida
      macroura [MD]), Eurasian collared-doves (Streptopelia decaocto [ECD]), white
      winged doves (Zenaida asiatica [WWD]), and common ground doves (Columbina
      passerina [CGD]), and 48 Inca doves (Columbina inca [ID]) were collected during
      the summer of 2006 and examined for helminths. Twelve helminth species were found
      (9 nematodes and 3 cestodes), representing 486 individuals. Nematodes numerically
      dominated the component community in all host species. Overall, helminth
      prevalence was similar among host sex within all dove species. However,
      prevalence of Skrjabinia bonini and Hymenolepis sp. in RPs was significantly
      different among host age groups (P = 0.01, P = 0.0002, respectively). Likewise,
      prevalence of Killigrewia delafondi was higher (P = 0.0001) in adult WWDs. Based
      on percent similarity and Jaccard's coefficient of community indices, helminth
      component communities were dissimilar, and the number of shared helminth species
      varied among host species. Data from this study suggest that the environment
      surrounding preferred host habitat and foraging strategies of each host species
      is the driving force behind helminth component communities. This study emphasizes
      the importance of examining co-occurring hosts at both local and regional scales
      to elucidate helminth community structure and patterns.

PMID- 21955249
TI  - The hepatic reductase null mouse as a model for exploring hepatic conjugation of
      xenobiotics: application to the metabolism of diclofenac.
AB  - The distribution, metabolism, excretion and hepatic effects of diclofenac were
      investigated following a single oral dose of 10 mg/kg to wild type and hepatic
      reductase null (HRN) mice. For the HRN strain the bulk of the [(14)C]-diclofenac
      related material was excreted in the urine/aqueous cagewash within 12 h of
      administration (~82%) with only small amounts eliminated via the faeces (~2% in
      24 h). Wild type mice excreted the radiolabel more slowly with ca. 52 and 15% of
      the dose recovered excreted in urine and faeces, respectively, by 24 h post dose.
      The metabolic profiles of the HRN mice were dominated by acyl conjugation to
      either taurine or glucuronic acid. Wild type mice produced relatively small
      amounts of the acyl glucuronide. Whole Body Autoradiography (WBA) of mice
      sacrificed at 24 h post dose indicated increased retention of radioactivity in
      the livers of HRN mice compared to wild type mice. Covalent binding studies
      showed no differences between the two strains. Metabolism of diclofenac in HRN
      mice involved mainly acyl glucuronide formation and taurine amide conjugation.
      This mouse model may find utility in understanding the impact of reactive
      metabolite formation via routes that involve the production of acyl-CoA or acyl
      glucuronides of acidic drugs.

PMID- 21955250
TI  - Genetic variability in apple fruit polyphenol composition in Malus * domestica
      and Malus sieversii germplasm grown in New Zealand.
AB  - Variations in the concentrations of flavan-3-ol, oligomeric procyanidin,
      chlorogenic acid, dihydrochalcone, flavonol, and anthocyanin polyphenol groups
      and total polyphenols were examined in the fruit peel and cortical flesh of 93
      (80 Malus * domestica and 13 Malus sieversii) apple genotypes in at least 1 year
      between 2003 and 2005 grown at one site in New Zealand (NZ). Differences among
      genotypes accounted for 46-97% of the total variation in the concentrations of
      total polyphenols and each of the individual phenol groups in the flesh and peel
      in both species, whereas effects of year and genotype * year were minimal, except
      for peel flavonols in M. * domestica and flesh flavonols in both species. In
      these cases, differences among genotypes accounted for less than 30% of the total
      variation, which was less than the variation found for the interaction between
      genotype and year. Total polyphenol concentrations among genotypes were spread
      over a 7- and 9-fold range in the flesh and a 4- and 3-fold range in the peel of
      M. sieversii and M. * domestica, respectively, with the spread in concentrations
      of individual polyphenol groups in each tissue and within each species varying
      from a 2-fold to over a 500-fold range. Higher concentrations were generally
      found in M. sieversii. In M. * domestica, cultivars and breeding selections
      originating in NZ had lower average flesh and peel total polyphenols and
      chlorogenic acid than older cultivars previously imported into NZ from overseas
      countries.

PMID- 21955252
TI  - Coping with challenging behaviours of children with autism: effectiveness of
      brief training workshop for frontline staff in special education settings.
AB  - BACKGROUND: The present study examined the effectiveness of three staff training
      elements: psychoeducation (PE) on autism, introduction of functional behavioural
      analysis (FBA) and emotional management (EM), on the reaction of challenging
      behaviours for frontline staff towards children with autism in Hong Kong special
      education settings. METHODS: A sample of 311 frontline staff in educational
      settings was recruited to one of the three conditions: control, PE-FBA and PE-FBA
      EM groups. A total of 175 participants completed all three sets of questionnaires
      during pre-training, immediate post-training and 1-month follow-up. RESULTS:
      Findings showed that the one-session staff training workshop increased staff
      knowledge of autism and perceived efficacy but decrease helping behavioural
      intention. CONCLUSIONS: In spite of the limited effectiveness of a one-session
      staff training workshop, continued staff training is still necessary for the
      improvement of service quality. Further exploration on how to change emotion
      response of staff is important.

PMID- 21955251
TI  - Designed antimicrobial and antitumor peptides with high selectivity.
AB  - We report a new class of cationic amphiphilic peptides with short sequences,
      G(IIKK)(n)I-NH(2) (n = 1-4), that can kill Gram-positive and Gram-negative
      bacteria as effectively as several well-known antimicrobial peptides and
      antibiotics. In addition, some of these peptides possess potent antitumor
      activities against cancer cell lines. Moreover, their hemolytic activities
      against human red blood cells (hRBCs) remain remarkably low even at some 10-fold
      bactericidal minimum inhibitory concentrations (MICs). When bacteria or tumor
      cells are cocultured with NIH 3T3 fibroblast cells, G(IIKK)(3)I-NH(2) showed fast
      and strong selectivity against microbial or tumor cells, without any adverse
      effect on NIH 3T3 cells. The high selectivity and associated features are
      attributed to two design tactics: the use of Ile residues rather than Leu and the
      perturbation of the hydrophobic face of the helical structure with the insertion
      of a positively charged Lys residue. This class of simple peptides hence offers
      new opportunities in the development of cost-effective and highly selective
      antimicrobial and antitumor peptide-based treatments.

PMID- 21955254
TI  - Unexpected prevalence of arthritis in women's right hip.

PMID- 21955253
TI  - Leptin promoter G-2548A genotypes and associated serum leptin levels in childhood
      acute leukemia at diagnosis and under high-dose steroid therapy.
AB  - Genotype/allele distributions of leptin promoter G-2548A polymorphism, serum
      leptin and insulin levels and body weight were not significantly different
      between 72 children (39 male/33 female; age range 1.08-16, median 6 years) with
      acute leukemia (56 acute lymphoblastic leukemia [ALL]/16 acute non-lymphoblastic
      leukemia [ANLL]) at diagnosis and 70 age- and sex-matched controls (p > 0.05).
      The - 2548GG genotype was associated with the highest leptin levels in controls
      and patients with acute leukemia after 7-day high-dose methylprednisolone (HDMP)
      therapy (p < 0.05), while no significant association of genotype with leptin
      levels was detected in patients at diagnosis (p > 0.05). One-week HDMP therapy in
      patients carrying the - 2548G allele caused a significant increase in leptin
      levels and body weight (p < 0.001), whereas increases in those carrying the -
      2548AA genotype were insignificant (p > 0.05). Decreases in white blood cell
      counts of patients after therapy were insignificant in - 2548GG (p > 0.05) yet
      significant in - 2548GA and - 2548AA (p < 0.05) genotypes. These results revealed
      no association of leptin genotype with the etiology of childhood acute leukemia
      but a possible association with leptin levels and effects of HDMP therapy.

PMID- 21955255
TI  - The role of ultrasonography in determining central venous patency in patients
      undergoing bowel transplantation.
AB  - Ultrasonography (US) is an attractive alternative for invasive studies to
      evaluate venous patency. However, little data exist concerning the usefulness of
      US in patients undergoing bowel transplantation. Twenty-five adult patients with
      bowel transplantation were retrospectively identified with both US and contrast
      venography (VG) performed preoperatively. The median age was 43 yr, and the
      median duration of total parenteral nutrition was 36 months. The vessels were
      evaluated as positive with >= 50% stenosis. Among the internal jugular veins and
      the subclavian veins examined with US (96% of the all sites) and with VG (69%),
      66 venous sites were available for comparison. VG confirmed positive in 42%
      (28/66), while US found positive in 27% (18/66); US had three false positives and
      13 false negatives, giving the sensitivity of 54% (95% confidence interval [CI],
      34-72) and the specificity of 92% (CI, 77-98). The positive and the negative
      likelihood ratios weighted by prevalence (42%) were 5 (CI, 1.7-14.3) and 0.37
      (CI, 0.23-0.60), respectively. In addition, VG confirmed stenosis in 32% of the
      right and 50% of the left brachiocephalic veins and 41% of the superior vena
      cava. US is not a reliable method for assessing the upper body venous system of
      patients undergoing bowel transplantation.

PMID- 21955256
TI  - Relationship of dyslipidemia and uric acid with the risk of myocardial infarction
      among hypertensive patients in Trinidad.
AB  - OBJECTIVES: To study the relationship of dyslipidemia and serum uric acid with
      the risk of myocardial infarction among the hypertensive type 2 diabetic and non
      diabetic patients of Trinidad. METHODS: Data were obtained from the hospital
      records of 672 adults who were treated for hypertension in public health clinics
      in Trinidad. RESULTS: The prevalence of myocardial infarction was 25.45% in the
      sample. Males accounted for 52.63% while females accounted for 47.37%.
      Hypertensive type 2 diabetics with dyslipidemia had greater occurrence of MI
      (23.93%) than non-diabetic hypertensive patients (7.67%) (p=0.008). Useful
      predictors of MI included: diabetes mellitus, altered lipid profile, family
      history of any cardiac conditions. On further analysis, hypertension class
      (p=0.003) and serum uric acid quartile (p=0.029) were also significant predictors
      of MI. CONCLUSIONS: The results suggest that there is a greater prevalence of MI
      in hypertensive type 2 diabetic patients with dyslipidemia than in non-diabetic
      hypertensive patients in Trinidad.

PMID- 21955257
TI  - Neutron pair distribution function study of two-line ferrihydrite.
AB  - Pair distribution function (PDF) analysis of neutron total scattering data from
      deuterated two-line ferrihydrite is consistent with the Keggin-related structural
      model for ferrihydrite published by Michel et al. (2007). Other models proposed
      in the literature, such as that of Drits et al. (1993), lead to inferior fits.
      Bond valence sums indicate that O(1) is bonded to a hydrogen atom, but the
      quality of the data is such that the exact position of the hydrogen could not be
      elucidated with confidence.

PMID- 21955258
TI  - New strain typing method with Sporothrix schenckii using mitochondrial DNA and
      polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP)
      technique.
AB  - The complete sequences of mitochondrial DNA (mtDNA) from two strains of different
      genotypes, American Type Culture Collection 10268 of mtDNA type 1 and KMU2025 of
      mtDNA type 4, were determined. These are circular molecules, 27 125 and 26 095 bp
      in length, respectively. The greatest difference between the two strains was
      found in the region encompassed by atp9 and cox2 genes, which was amplified with
      polymerase chain reaction (PCR) and used for preliminary restriction fragment
      length polymorphism (RFLP) analysis. Eight isolates of five mtDNA types were used
      and RFLP patterns obtained with the restriction enzyme AseI showed that this
      method seems to have greater discrimination power than the other PCR-RFLP typing
      method using internal transcribed spacer regions of nuclear DNA.

PMID- 21955259
TI  - Cannabinoid-1 receptor antagonist rimonabant (SR141716) increases striatal
      dopamine D2 receptor availability.
AB  - The cannabinoid 1 receptor antagonist rimonabant (SR141716) alters rewarding
      properties and intake of food and drugs. Additionally, striatal dopamine D2
      receptor (DRD2) availability has been implicated in reward function. This study
      shows that chronic treatment of rats with rimonabant (1.0 and 3.0 mg/kg/day) dose
      dependently increased DRD2 availability in the dorsal striatum (14 and 23%)
      compared with vehicle. High-dose rimonabant also increased DRD2 availability in
      the ventral striatum (12%) and reduced weight gain. Thus, up-regulation of
      striatal DRD2 by chronic rimonabant administration may be an underlying mechanism
      of action and confirms the interactions of the endocannabinoid and dopaminergic
      systems. 

PMID- 21955260
TI  - The role of physiology in the divergence of two incipient cichlid species.
AB  - Sexual selection on male coloration has been implicated in the evolution of
      colourful species flocks of East African cichlid fish. During adaptive
      radiations, animals diverge in multiple phenotypic traits, but the role of
      physiology has received limited attention. Here, we report how divergence in
      physiology may contribute to the stable coexistence of two hybridizing incipient
      species of cichlid fish from Lake Victoria. Males of Pundamilia nyererei (males
      are red) tend to defeat those of Pundamilia pundamilia (males are blue), yet the
      two sibling species coexist in nature. It has been suggested that red males bear
      a physiological cost that might offset their dominance advantage. We tested the
      hypothesis that the two species differ in oxidative stress levels and immune
      function and that this difference is correlated with differences in circulating
      steroid levels. We manipulated the social context and found red males experienced
      significantly higher oxidative stress levels than blue males, but only in a
      territorial context when colour and aggression are maximally expressed. Red males
      exhibited greater aggression levels and lower humoral immune response than blue
      males, but no detectable difference in steroid levels. Red males appear to trade
      off increased aggressiveness with physiological costs, contributing to the
      coexistence of the two species. Correlated divergence in colour, behaviour and
      physiology might be widespread in the dramatically diverse cichlid radiations in
      East African lakes and may play a crucial role in the remarkably rapid speciation
      of these fish.

PMID- 21955261
TI  - The development of a parenting program for incarcerated mothers in Australia: a
      review of prison-based parenting programs.
AB  - The increasing population of children with an incarcerated parent is a
      significant public health issue. A literature search highlighted that children of
      incarcerated parents experience psychological stressors that may potentially
      impact on health and behavioural outcomes. Parenting programs for prisoners may
      be of benefit as early parenting experiences during childhood have a significant
      impact on a child's future experiences as an adolescent and adult. A review of
      identified evaluation-based studies of parenting programs for prisoners (N = 11),
      although varied in program delivery approaches and evaluation methods, suggest
      that such programs have the potential to improve the parenting skills, knowledge
      and confidence of incarcerated parents. Finally, this paper provides an outline
      of the development of an Australian based parenting program for incarcerated
      mothers and their young children.

PMID- 21955262
TI  - 'Walk-ins': developing a nursing role to manage unscheduled presentations to a
      community mental health clinic.
AB  - This paper reports on the evolution of the role of a 'walk-in' nurse at an
      Australian urban community mental health clinic. Despite the lack of any
      indication that a walk-in service was available, people persisted in presenting
      to the community mental health clinic requesting immediate help. A nursing
      position was therefore established to assess people presenting as walk-ins and
      address the issues identified. Data was collected over a 33 week period. Many
      people presented with social issues, and about half were referred to agencies
      outside the mental health system. A number of difficulties in the nursing role
      were identified including the variable workload, problems obtaining adequate
      clinical supervision, and lack of clarity about the place of the service within
      the established pathways to care. With further development, the mental health
      walk-in clinic role would be suitable for a nurse practitioner. Our study
      suggested that a walk-in clinic is preferred by many consumers, is efficient in
      terms of staff time, and is able to provide a high quality service responding to
      a wide range of presenting problems.

PMID- 21955263
TI  - A path of perpetual resilience: exploring the experience of a diabetes-related
      amputation through grounded theory.
AB  - Little research has been done on the experience of diabetes-related amputation.
      The aim of this study was to allow amputees to describe their experiences of
      amputation and to generate grounded theory that will lead health professionals
      towards a more comprehensive understanding of the realities of post-amputation
      life. Unstructured interviews were conducted with five participants with a
      diabetes-related amputation living in a rural setting, and their respective
      carers. The interviews were analysed using Grounded Theory methods. Data analysis
      revealed three categories: 'imposed powerlessness', 'adaptive functionality' and
      'endurance'. The impact of participant's amputations were influenced by
      continuing limb problems post-amputation and co-existing complications affecting
      their physical function. Medical errors and lack of awareness of the risks for
      diabetic amputations resulted in uncertainty and fear. The participants' sense of
      grief, loss and shock post operatively continued later as they came to terms with
      their awkwardness of movement, yet they moved forward developing their own sense
      of hope through a coping process that revealed remarkable ability to endure and
      exert control over lives that seemed to be at the whim of an ongoing disease
      process. The substantive theory resulting from this grounded theory study was
      conceptualised as 'A Path of Perpetual Resilience'. It is important that
      psychosocial and not just physical adjustment is considered an indicator for
      determining outcomes for these people, and that future care involves strategies
      to promote this. A greater sample size is required to determine if these findings
      are transferable to the general diabetes-related amputation population.

PMID- 21955264
TI  - A mixed method pilot study: the researchers' experiences.
AB  - AIM: This paper reports on the outcomes of a small well designed pilot study.
      BACKGROUND: Pilot studies often disseminate limited or statistically meaningless
      results without adding to the body knowledge on the comparative research
      benefits. METHOD: The design a pre-test post-test group parallel randomised
      control trial and inductive content analysis of focus group transcripts was
      tested specifically to increase outcomes in a proposed larger study. OUTCOMES:
      Strategies are now in place to overcome operational barriers and recruitment
      difficulties. Links between the qualitative and quantitative arms of the proposed
      larger study have been made; it is anticipated that this will add depth to the
      final report. CONCLUSION: More extensive reporting on the outcomes of pilot
      studies would assist researchers and increase the body of knowledge in this area.

PMID- 21955265
TI  - Sex differences in gender characteristics of Australian nurses and male
      engineers: a comparative cross-sectional survey.
AB  - There continue to be assumptions within the nursing literature that nursing is
      synonymous with a feminine sex role identity. A comparative cross-sectional
      survey consisting of the Bem Sex Role Inventory and the Australian sex role scale
      was used to determine sex difference in gender characteristics of Australian
      nurses and with male engineers. A statistically significant difference in
      femininity was found between all the samples (F((2,908)) = 20.24, p < 0.00001;
      F((2,908)) = 60.13, p < 0.00001). A statistical difference in masculinity was
      found between female nurses and the two male samples on the two masculine scales
      (F((2,908)) = 12.48, p < 0.000001; F((2,908)) = 6.94, p = 0.001). Path analysis
      found strong significant direct relationships between the samples and expressive
      orientation (t = 27.67) and self display (t = 12.42). Whilst differences in
      expressive characteristics were found between male and female nurses, a similar
      difference was found between male nurses and male engineers, supporting the
      notion that male nurses perceive themselves as having feminine characteristics
      essentially required for nursing.

PMID- 21955266
TI  - Theory before practice: implicit assumptions about clinical nursing education in
      Australia as revealed through a shared critical reflection.
AB  - The transfer of nursing education into the higher education sector occurred over
      a 10-year period in Australia (1985-1994). Australian nurse leaders settled on a
      single outcome measure to be applied for all nursing graduates in the form of
      national competency standards. While this move enabled diversity, the lack of
      consistency in curriculum design has subsequently led to increasing confusion for
      clinicians who support students' learning in clinical placements. Using a shared
      critical reflection method, the authors reviewed (1) the evaluation comments from
      nurses in one nursing unit of a hospital in one Australian jurisdiction and (2)
      an historical review of nursing literature at the time of the transfer of nursing
      education into the higher education sector. The reflection suggests that the aim
      of the transfer, to create critical thinking graduates, has been undermined by
      the implicit clinical education practices that have since emerged. In order to
      address the contemporary challenges for clinical staff working with students from
      multiple universities, as well as increased student numbers to address the
      nursing shortage, we recommend a new approach to curriculum design: a national
      clinical curriculum drawn from social, as well as cognitive, learning theory that
      at once informs clinicians of students' potential abilities and provides the
      scope to accommodate the increasingly difficult and critical learning
      requirements of tertiary-based nursing students.

PMID- 21955267
TI  - Reasons for leaving nursing: a study among Turkish nurses.
AB  - BACKGROUND: Reasons for the growing nursing shortage are often complex and
      multidimensional. AIM: To explore the phenomenon of why Turkish nurses leave
      nursing. METHODS: The sample in this descriptive study was 134 nurses who had
      left the profession. A snowball sampling method was used to identify subjects and
      multiple methods were used to elicit reasons for leaving. Data analysis included
      descriptive statistics. RESULTS: The main reasons for leaving nursing were
      related to unsatisfactory working conditions and a negative perception of
      nursing. Of the respondents, 69.4% received education in a non-nursing field. The
      most popular career choice was teaching (27.6%). The results of this study
      indicate that working conditions and public opinion adversely affect a nurse's
      interest in the profession. CONCLUSIONS: The results of the study indicate a need
      to improve working conditions and to approach this subject from a
      multidimensional perspective.

PMID- 21955268
TI  - Meanings and aspects of quality of life for cancer patients: a descriptive
      exploratory qualitative study.
AB  - Given the importance of quality of life (QoL) for cancer patients, it is
      important to work out what this concept means not only for cancer patients, and
      for the nurses who care for them, but also the aspects of which it is composed.
      Therefore, an interpretive research study was conducted to explore in-depth
      meanings and aspects of QoL as expressed by cancer nurses. Participants were
      selected from different inpatient and outpatient oncology services and a
      palliative setting in Adelaide, South Australia. Results showed that many aspects
      contribute to an individual's QoL. These include the physical, the psychological,
      the spiritual, and both environmental and social interactions. More importantly,
      participants stated that spirituality is multifaceted and that there may be
      aspects in life that may be taken for granted. The meaning of patients' QoL was
      viewed by nurses as a patient's overall happiness and satisfaction. Also, nurses
      identified that providing choices to patients made an important contribution to a
      patient's QoL. Therefore, this exploration into the in-depth meanings and aspects
      of QoL for cancer patients from nurses' perspectives identified that, in addition
      to the aspects related to QoL that have been identified previously in the
      literature, aspects related to spirituality would need to be extensively covered,
      and providing choices to patients would be important in patients' QoL in an
      Australian setting.

PMID- 21955269
TI  - Cultural and linguistic isolation: the breast cancer experience of Chinese
      Australian women - a qualitative study.
AB  - OBJECTIVES: Although Chinese-Australian women are at higher risk of developing
      breast cancer after migration to Australia, information on their experience is
      limited. This paper explores Chinese-Australian women's perceptions of the
      meaning and experience of a breast cancer diagnosis, treatment and coping
      mechanism. METHODS: Three focus groups were conducted with 23 Chinese-Australian
      women diagnosed with breast cancer in their native language (Cantonese or
      Mandarin). Following transcription and translation, interview data was analysed
      by content analysis. RESULTS: Culturally specific values, beliefs and language
      barriers played a significant role in shaping the women's breast cancer
      experiences and their response to the diagnosis. Of note these women found the
      experience isolating and distressing, factors that were compounded by the lack of
      culturally sensitive resources and information. CONCLUSIONS: In providing
      information for Chinese-Australian women with breast cancer, culture, language
      and migration experience need to be taken into account.

PMID- 21955270
TI  - The role of religiosity as a coping resource for relatives of critically ill
      patients in Greece.
AB  - Critical care hospitalisation is emotionally overwhelming for the relatives of
      patients. Research has shown that religiosity is an effective coping resource for
      people with health related problems and has been correlated with better health
      outcomes. However the processes by which religiosity is utilized and its effects
      on relatives of critically ill patients have not been adequately explored. This
      article presents relatives' experiences and processes of religiosity; it is part
      of a wider grounded theory study on the experiences of critically ill patients'
      relatives in Greece. Twenty-five relatives of patients in the intensive care
      units of three public general district hospitals in Athens, Greece, participated
      in 19 interviews. Religiosity was found to be the main source of hope, strength
      and courage for relatives and was expressed with church/monastery attendance,
      belief in God, praying, and performing religious rituals. Health care
      professionals should pay attention and understand these aspects of coping.

PMID- 21955271
TI  - Quality of work life and productivity among Iranian nurses.
AB  - Nurses are amongst the employees whose lives are fully affected by the quality of
      work life (QWL) as a consequence of dynamic changes in work environment.
      Excessive workload and poor work conditions are focal issues in nursing. The QWL
      assessment is an important and basic effort to deal with this issue. Moreover,
      staff productivity is a worthy goal of organizations tending to grow. If the
      relationship between the QWL and productivity becomes apparent, managers can
      provide conditions for promoting the QWL for personnel to be productive. To our
      knowledge, these variables and their relationships have not been studied yet
      among Iranian nurses. This descriptive study was carried out to investigate the
      relationship between the QWL and productivity among 360 clinical nurses working
      in the hospitals of Tehran University of Medical Sciences. Findings showed that
      the QWL is at a moderate level among 61.4% of the participants. Only 3.6% of the
      nurses reported that they were satisfied with their works. None of those who
      reported the productivity as low reported their work life quality to be
      desirable. Spearman-rho test showed a significant relationship between
      productivity and one's QWL (p < 0.001). Considering the results, managers should
      adopt appropriate policies to promote the QWL and productivity.

PMID- 21955272
TI  - Outcomes of a clinical partnership model for undergraduate nursing students.
AB  - BACKGROUND: Over the last decade several innovative approaches to enhance
      students' transition to graduate nurse year have been implemented or piloted.
      This paper describes a study that investigated how the social practices of
      clinical partnership placement model underpin workplace learning for
      undergraduate students as they transitioned to graduate. METHODS: A mixed method
      approach was utilized comprising individual interviews with students, observation
      of clinical workplaces across six different areas of nursing practice, student
      surveys of the clinical learning environment and participant workshops. RESULTS:
      Three themes were identified that influenced participants' preparedness for work
      and enhanced the transition into the workplace: 'organizational familiarity',
      'continuity' and 'social participation'. CONCLUSION: A clinical partnership model
      offers a degree of work readiness for novices when commencing their professional
      practice role. It enables individuals to participate and engage in workplace
      activities which are a central component of their learning.

PMID- 21955273
TI  - Enantioselective synthesis of endohedral metallofullerenes.
AB  - Endohedral metallofullerenes are promising materials in biomedical and material
      sciences. In particular, they are of interest as agents for magnetic resonance
      imaging (MRI), photovoltaic devices, and semimetallic components. The synthesis
      of chiral endofullerenes represents one step further in the potential use of
      these carbon allotropes; however, this step has not been addressed so far. In
      this regard, enantiopure endofullerenes are expected to open new avenues in
      fields in which chirality is a key issue. Here, the synthesis and
      characterization of the first chiral endohedral metallofullerenes, namely, chiral
      bis-adducts of La@C(72), are reported. Eight optically active isomers were
      obtained by enantioselective 1,3-dipolar cycloaddition of a N-metalated
      azomethine ylide onto a non-isolated-pentagon rule metallofullerene derivative,
      La@C(72)(C(6)H(3)Cl(2)), catalyzed by a copper chiral complex. The chiral bis
      adducts of La@C(72), isolated by nonchiral HPLC, showed optical purities as high
      as 98% as revealed by the remarkable positive or negative Cotton effects observed
      in the circular dichroic spectra.

PMID- 21955274
TI  - Investigation on the solubility of SO2 and CO2 in imidazolium-based ionic liquids
      using NPT Monte Carlo simulation.
AB  - The solubility of sulfur dioxide (SO(2)) and carbon dioxide (CO(2)) at P = 1 bar
      in a series of imidazolium-based room-temperature ionic liquids (RTILs) is
      calculated by Monte Carlo simulation in NPT ensemble using the OPLS-UA force
      field and Widom particle insertion method. The studied ILs were 1-butyl-3
      methylimidazolium ([bmim](+)) tetrafluoroborate ([BF(4)](-)), [bmim](+)
      hexafluorophosphate ([PF(6)](-)), [bmim](+) bromide ([Br](-)), [bmim](+) nitrate
      ([NO(3)](-)), [bmim](+) bis-(trifluoromethyl) sulfonylimide ([Tf2N](-)), and 1
      ethyl-3-methylimidazolium tetrafluoroborate ([emim][BF(4)]). To validate the
      simulations, the liquid density of studied ILs and the solubility of CO(2) in
      [bmim][PF(6)] was compared with corresponding experimental and theoretical
      studies reported in the literature, and a good agreement was obtained. The
      results of SO(2) solubility demonstrate that the SO(2) gas has the highest
      solubility in [bmim][NO(3)] and [bmim][Br] ILs and the lowest solubility in
      [bmim][PF(6)]. To describe the solubility order of polar gases such as SO(2) and
      nonpolar gases like CO(2), we have simulated the SO(2)/IL and CO(2)/IL mixtures
      which made possible to investigate the interaction of solute molecules with
      anions and cations in the liquid phase. We introduced the ratio of solute-IL
      interaction over cation-anion interaction energy density as an index for
      solubility of gases in ILs. The results show that the proposed index can describe
      the solubility order of SO(2) as well as CO(2) and it might be used as an
      alternative to standard methods of infinite dilution Henry's constant
      calculations when the solubility order is desired.

PMID- 21955275
TI  - Cytopathological findings in a siderotic liver nodule.

PMID- 21955276
TI  - Lysine demethylases inhibitors.

PMID- 21955277
TI  - A narrow QRS tachycardia with irregular atrial and ventricular intervals and VA
      dissociation: what is the mechanism?

PMID- 21955278
TI  - Seroprevalence of Neospora caninum infection on dairy cattle in farms from
      southern Romania.
AB  - Neospora caninum, a coccidian parasite closely related to Toxoplasma gondii, is
      one of the major causes of abortion in cattle worldwide. Conventional serological
      techniques, such as the indirect fluorescent antibody test and enzyme-linked
      immunosorbent assay (ELISA), are routinely used in adult animals and aborted
      fetuses for the detection of anti- N. caninum antibodies. In Romania, infection
      with N. caninum in cattle has been reported recently, but only in limited areas
      from the north and central parts of the country. Therefore, the aim of this study
      was to obtain additional seroepidemiological data on infection with N. caninum on
      dairy farms from the south of Romania. A total of 258 blood samples was analyzed
      from 230 dairy cows and 28 calves from 9 dairy farms in southern Romania; the
      presence of specific IgG antibodies against N. caninum was determined using an
      indirect ELISA test. The average seroprevalence was 40.3%, but the within-herd
      prevalence ranged between 11.5 and 80.0%; the seroprevalence in dairy cows was
      41.7%, while in calves it was 28.6%. Of the positive samples, 74.0% (77/104) had
      a high positive reaction (S/P ratio more than 1.0), while 26.0% (27/104) had a
      low positive reaction (S/P ratio between 0.5 and 1.0). This study indicates that
      N. caninum infection is widespread in the south of Romania, which could explain
      the causes of abortions registered in some herds in the studied area. However, a
      serological screening across the country is planned in order to assess the actual
      national prevalence of N. caninum infection, followed by implementation of a
      prevention and control program.

PMID- 21955280
TI  - Screening for urinary tract infection in women with hyperemesis gravidarum.
AB  - AIM: The aim of this study was to evaluate urine microscopy, dipstick analysis
      and urinary symptoms in screening for urinary tract infection (UTI) in
      hyperemesis gravidarum (HG). MATERIALS AND METHODS:   A prospective cross
      sectional study was performed on women at first hospitalization for HG. A clean
      catch mid-stream urine sample from each recruit was sent for microscopy (for
      bacteria, leucocytes and erythrocytes), dipstick analysis (for leukocyte
      esterase, nitrites, protein and hemoglobin) and microbiological culture. The
      presence of current urinary symptoms was elicited by questionnaire. UTI is
      defined as at least 10(5) colony-forming units/mL of a single uropathogen on
      culture. Screening test parameters were analyzed against UTI. RESULTS: UTI was
      diagnosed in 15/292 subjects (5.1%). Receiver-operator characteristic curve
      analysis of microscopic urine leucocytes revealed area under the curve=0.64, 95%
      confidence interval (CI) 0.5-0.79, P=0.063 and erythrocytes area under the
      curve=0.53, 95%CI 0.39-0.67, P=0.67 for UTI indicating the limited screening
      utility of these parameters. Microscopic bacteriuria (likelihood ratio [LR] 1.1,
      95%CI 0.7-1.5) and urine dipstick leukocyte esterase (LR 1.4, 95%CI 1.1-1.8),
      nitrites (LR 2.3, 95%CI 0.3-17.2), protein (LR 1.0, 95%CI 0.7-1.6) and hemoglobin
      (LR 0.8, 95%CI 0.4-1.5) were not useful screening tests for UTI in HG. Elicited
      symptoms were also not predictive of UTI. CONCLUSION: Urine microscopy, dipstick
      analysis and urinary symptoms were not useful in screening for UTI in HG. UTI
      should be established by urine culture in HG before starting antibiotic
      treatment.

PMID- 21955279
TI  - FluoroSpot Analysis of TLR-Activated Monocytes Reveals Several Distinct Cytokine
      Secreting Subpopulations.
AB  - Monocytes have long been considered a heterogeneous group of cells both in terms
      of morphology and function. In humans, three distinct subsets have been described
      based on their differential expression of the cell surface markers CD14 and CD16.
      However, the relationship between these subsets and the production of cytokines
      has for the most part been based on ELISA measurements, making it difficult to
      draw conclusions as to their functional profile on the cellular level. In this
      study, we have investigated lipoteichoic acid (LTA)- and lipopolysaccharide (LPS)
      induced cytokine secretion by monocytes using the FluoroSpot technique. This
      method measures the number of cytokine-secreting cells on the single-cell level
      and uses fluorescent detection, allowing for the simultaneous analysis of two
      cytokines from the same population of isolated cells. By this approach, human
      monocytes from healthy volunteers could be divided into several subgroups as IL
      1beta, IL-6, TNF-alpha and MIP-1beta were secreted by larger populations of
      responding cells (25.9-39.2%) compared with the smaller populations of GM-CSF
      (9.1%), IL-10 (1.3%) and IL-12p40 (1.2%). Furthermore, when studying co-secretion
      in FluoroSpot, an intricate relationship between the monocytes secreting IL-1beta
      and/or IL-6 and those secreting TNF-alpha, MIP-1beta, GM-CSF, IL-10 and IL-12p40
      was revealed. In this way, dissecting the secretion pattern of the monocytes in
      response to TLR-2 or TLR-4 stimulation, several subpopulations with distinct
      cytokine-secreting profiles could be identified. 

PMID- 21955281
TI  - Increased LCAT activity and hyperglycaemia decrease the antioxidative
      functionality of HDL.
AB  - BACKGROUND: Type 2 diabetes mellitus increases the risk of atherosclerotic
      cardiovascular disease. Antioxidative properties of high density lipoprotein
      (HDL) are important for atheroprotection. This study investigated whether the
      antioxidative functionality of HDL is altered in type 2 diabetes mellitus and
      aimed to identify potential determinants of this parameter. MATERIALS AND
      METHODS: In a cross-sectional study, we investigated 74 patients with type 2
      diabetes and 75 control subjects. Antioxidative properties of HDL were measured
      and expressed as either (i) HDL antioxidative capacity or (ii) HDL antioxidation
      index after multiplying HDL antioxidative capacity results with individual plasma
      HDL cholesterol concentrations. Lecithin:cholesterol acyltransferase (LCAT) and
      paraoxonase-1 (PON-1) activities were determined. RESULTS: HDL antioxidative
      capacity was similar in patients with diabetes and controls, while the HDL
      antioxidation index was decreased in patients with diabetes (P = 0.005) owing to
      lower plasma HDL cholesterol (P < 0.001). LCAT activity was higher and PON-1
      activity lower in type 2 diabetes mellitus (each P < 0.001). In the combined
      subjects, HDL antioxidative capacity was inversely related to LCAT activity (P <
      0.01). The HDL antioxidation index correlated negatively with blood glucose (P <
      0.001), HbA1c and LCAT activity (each P < 0.01), and positively with PON-1
      activity (P < 0.01). Multiple linear regression analysis demonstrated that high
      LCAT activity was associated with both decreased HDL antioxidation capacity (P <
      0.05) and index (P < 0.001) independent of diabetes status, glycaemic control and
      PON-1. CONCLUSIONS: Overall, the antioxidative functionality of HDL is impaired
      in type 2 diabetes mellitus mostly because of lower HDL cholesterol.
      Hyperglycaemia, increased LCAT activity and lower PON-1 activity likely
      contribute to impaired antioxidative functionality of HDL.

PMID- 21955282
TI  - Paving the way for post-master's DNP graduates in clinical gerontological
      leadership.

PMID- 21955286
TI  - Evaluation of nonpolar metabolites in plant extracts by 13C NMR spectroscopy.
AB  - (13)C nuclear magnetic resonance (NMR) spectroscopy was explored as a simple and
      efficient technique for the quantitative analysis of nonpolar metabolites in
      plants. The method was first optimized with a mixture of known metabolites and
      then applied to the nonpolar leaf extracts of plants harvested in the Valencian
      community (eastern Spain) belonging to three different genera: Euphorbia
      (Euphorbiaceae), Araujia (Apocynaceae), and Morus (Moraceae). Furthermore, an
      exhaustive analysis of  Euphorbia characias  leaf and stem extracts from
      different geographic locations allowed that quantitative (13)C NMR spectroscopy
      is a suitable tool for metabolic profiling purpose.

PMID- 21955287
TI  - People with mild to moderate intellectual disability talking about their diabetes
      and how they manage.
AB  - BACKGROUND: The prevalence of diabetes is relatively high in people with
      intellectual disability (ID). However, little is known about how people with ID
      experience having diabetes and how they manage the condition. METHOD: Seventeen
      people with mild to moderate ID who have diabetes were interviewed. A framework
      on illness perceptions having an influence on diabetes self-management was used
      as a basis for the interviews and for the qualitative analysis. RESULTS: Diabetes
      is associated with feelings of loss with regard to food intake and choices, and
      with being controlled. Most respondents did not feel ill. Information about
      diabetes for people with ID is lacking, but they do have questions. Family
      members with diabetes often serve as a role model. Diabetes self-management is
      impeded by a lack of information, motivation and support, few opportunities for
      learning, and by health factors, mood and living accommodation. Communication
      between health professionals and people with ID about diabetes rarely takes
      place. CONCLUSIONS: Developing diabetes information together with the people
      concerned is an important step towards engagement in self-management activities.
      At the same time, the professional staff in living arrangements should stimulate
      and support the development of self-management skills in people with diabetes, by
      providing opportunities to learn and develop. Therefore, the professional staff
      also need skills and information to be able to support people with ID in building
      the skills and confidence they need to lead active and fulfilling lives, despite
      having diabetes.

PMID- 21955288
TI  - NMR analysis of the fibronectin cell-adhesive sequence, Arg-Gly-Asp, in a
      recombinant silk-like protein and a model peptide.
AB  - It is well established that by introducing the cell-adhesive sequence Arg-Gly-Asp
      (RGD) from fibronectin into Bombyx mori silk fibroin by covalent coupling or
      bioengineering techniques, excellent biomaterials have been developed with the
      modified silk fibroin. However, there is no report about the structure and
      dynamics of the RGD moiety in the silk fibroin. To clarify the origin of such a
      high cell adhesion character and to design new recombinant silk protein with
      higher cell adhesion ability, it is necessary to characterize the structure and
      dynamics of the RGD moiety introduced into silk fibroin. In this study, the
      structure and dynamics of the RGD moiety in a recombinant silk-like protein,
      SLPF(10), consisting of the repeated silk fibroin sequence (AGSGAG)(3) and the
      sequence ASTGRGDSPA including the RGD moiety, were studied using solution NMR.
      The (1)H, (15)N, and (13)C chemical shifts indicate that the RGD moiety, as well
      as the silk fibroin sequence, takes a random coil form with high mobility in
      aqueous solution. Next, a (13)C solid-state NMR study was performed on a (13)C
      selectively labeled model peptide, AGSGAG[3-(13)C]A(7)GSGAGAGSGGT[2
      (13)C]G(19)R[1-(13)C]G(21)DSPAGGGAGAGSGAG. After formic acid treatment, an
      increase in the beta-sheet fraction for the AGSGAG sequence and peak narrowing of
      the residues around the RGD moiety were observed in the dry state. The latter
      indicates a decrease in the chemical shift distribution although the RGD moiety
      is still in random coil. A decrease in the peak intensities of the RGD moiety in
      the swollen state after immersing it in distilled water was observed, indicating
      high mobility of the RGD sequence in the peptide in the swollen state. Thus, the
      random coil state of the RGD moiety in the recombinant silk-like protein is
      maintained in aqueous solution and also in both dry and swollen state. This is
      similar to the case of the RGD moiety in fibronectin. The presence of the linker
      ASTG at the N-terminus and SPAGG at the C-terminus seems important to maintain
      the random coil form and the flexible state of the RGD sequence in order to
      permit access for binding to various integrins.

PMID- 21955289
TI  - Diclofenac metabolism in the mouse: novel in vivo metabolites identified by high
      performance liquid chromatography coupled to linear ion trap mass spectrometry.
AB  - The metabolism of [(14)C]-diclofenac in mice was investigated following a single
      oral dose of 10 mg/kg. The majority of the drug-related material was excreted in
      the urine within 24 h of administration (49.7 %). Liquid chromatographic analyses
      of urine and faecal extracts revealed extensive metabolism to at least 37
      components, with little unchanged diclofenac excreted. Metabolites were
      identified using a hybrid linear ion-trap mass spectrometer via exact mass
      determinations of molecular ions and subsequent multi-stage fragmentation. The
      major routes of metabolism identified included: 1) conjugation with taurine; and
      2) hydroxylation (probably at the 4'-and 5-arene positions) followed by
      conjugation to taurine, glucuronic acid or glucose. Ether, rather than acyl
      glucuronidation, predominated. There was no evidence for p-benzoquinone-imine
      formation (i.e. no glutathione or mercapturic acid conjugates were detected). A
      myriad of novel minor drug-related metabolites were also detected, including
      ribose, glucose, sulfate and glucuronide ether-linked conjugates of hydroxylated
      diclofenac derivatives. Combinations of these hydroxylated derivatives with acyl
      conjugates (glucose, glucuronide and taurine) or N-linked sulfation or
      glucosidation were also observed. Acyl- or amide-linked-conjugates of benzoic
      acid metabolites and several indolinone derivatives with further hydroxylated and
      conjugated moieties were also evident. The mechanisms involved in the generation
      of benzoic acid and indolinone products indicate the formation reactive
      intermediates in vivo that may possibly contribute to hepatotoxicity.

PMID- 21955290
TI  - Guest comment: perfluoroalkyl acid focus issue.

PMID- 21955291
TI  - Mature natural killer cell lymphoma with an unusual immunophenotype: CD16-, CD56
      , and CD57 negative.

PMID- 21955292
TI  - Circulating plasma cells predict the outcome of relapsed or refractory multiple
      myeloma.
AB  - Pretreatment detection of peripheral blood malignant circulating plasma cells
      (CPCs) has been shown to be of negative prognostic value in multiple myeloma
      (MM). We hypothesized that the assessment of CPC kinetics in response to one
      therapy cycle using six-color flow cytometry could be helpful in the early
      detection of MM refractoriness to treatment. Forty-two patients with refractory
      or relapsed (RR) MM were enrolled. Median time to tumor progression (TTP) of 51
      days and median overall survival (OS) of 308 days was shortest in patients whose
      CPCs with aberrant phentoype (aCPCs) did not decrease after one therapy cycle
      compared to patients with decreasing (median TTP 258 days and OS 856 days) or
      undetectable (median TTP 581 days and OS 1006 days) aCPCs (p < 0.001 and p =
      0.007 for TTP and OS, respectively). Non-reduction of aCPCs in patients with RR
      MM after the first cycle of therapy may be useful in early identification of
      patients resistant to a given therapy.

PMID- 21955293
TI  - Women who experience obstetric haemorrhage are at higher risk of anaemia, in both
      rich and poor countries.
AB  - OBJECTIVES: Anaemia is a potential long-term sequel of obstetric blood loss, but
      the increased risk of anaemia in women who experience a haemorrhage compared to
      those who do not has not been quantified. We sought to quantify this risk and
      explore the duration of increased risk for these women. METHODS: Systematic
      review of articles published between 1990 and 2009. Data were analysed by high-
      and low-income country groupings. Prevalence and incidence ratios, and mean
      haemoglobin levels were compared. RESULTS: Eleven of 822 studies screened were
      included in the analysis. Most studies showed a higher prevalence or incidence of
      anaemia in women who had experienced haemorrhage than in those who did not,
      irrespective of the timing of measurement post-partum. In high-income countries,
      women who had a haemorrhage were at 5.68 (95% CI 5.04-6.40) times higher risk of
      post-partum anaemia than women who did not. In low-income countries, the
      prevalence of anaemia was 1.58 (95% CI 0.96-2.60) times higher in women who had a
      haemorrhage than in women who did not, although this ratio was greater when the
      study including mild anaemia in its definition of anaemia was excluded (1.93, 95%
      CI 1.42-2.62). Population-attributable fractions ranged from 14.9% to 39.6%.
      Several methodological issues, such as definitions, exclusion criteria and timing
      of measurements, hindered the comparability of study results. CONCLUSIONS: Women
      who experience haemorrhage appear to be at increased risk of anaemia for many
      months after delivery. This important finding could have serious implications for
      their health care and management.

PMID- 21955294
TI  - Hydrogen sulphide-releasing diclofenac derivatives inhibit breast cancer-induced
      osteoclastogenesis in vitro and prevent osteolysis ex vivo.
AB  - BACKGROUND AND PURPOSE: Hydrogen sulphide (H(2)S) and prostaglandins are both
      involved in inflammation, cancer and bone turnover, and non-steroidal anti
      inflammatory drugs (NSAIDs) and H(2)S donors exhibit anti-inflammatory and anti
      tumour properties. H(2)S-releasing diclofenac (S-DCF) derivatives are a novel
      class of NSAIDs combining the properties of a H(2)S donor with those of a
      conventional NSAID. EXPERIMENTAL APPROACH: We studied the effects of the S-DCF
      derivatives ACS15 and ACS32 on osteoclast and osteoblast differentiation and
      activity in vitro, human and mouse breast cancer cells support for osteoclast
      formation and signalling in vitro, and osteolysis ex vivo. KEY RESULTS: The S
      diclofenac derivatives ACS15 and ACS32 inhibited the increase in osteoclast
      formation induced by human MDA-MB-231 and MCF-7 and mouse 4T1 breast cancer cells
      without affecting breast cancer cell viability. Conditioned media from human MDA
      MB-231 cells enhanced IkappaB phosphorylation and osteoclast formation and these
      effects were significantly inhibited following treatment by ACS15 and ACS32,
      whereas the parent compound diclofenac had no effects. ACS15 and ACS32 inhibited
      receptor activator of NFkappaB ligand-induced osteoclast formation and
      resorption, and caused caspase-3 activation and apoptosis in mature osteoclasts
      via a mechanism dependent on IKK/NFkappaB inhibition. In calvaria organ culture,
      human MDA-MB-231 cells caused osteolysis, and this effect was completely
      prevented following treatment with ACS15 and ACS32. CONCLUSIONS AND IMPLICATIONS:
      S-diclofenac derivatives inhibit osteoclast formation and activity, suppress
      breast cancer cell support for osteoclastogenesis and prevent osteolysis. This
      suggests that H(2)S-releasing diclofenac derivatives exhibit anti-resorptive
      properties, which might be of clinical value in the treatment of osteolytic bone
      disease.

PMID- 21955295
TI  - Comparison of preload-sensitive pressure and flow controller strategies for a
      dual device biventricular support system.
AB  - The use of rotary left ventricular assist devices (LVADs) has extended to
      destination and recovery therapy for end-stage heart failure. Incidence of right
      ventricular failure while on LVAD support requires a second device be implanted
      to support the failing right ventricle. Without a commercially available
      implantable rotary right ventricular assist device, rotary LVADs are cannulated
      into the right heart and operation modified to provide suitable support for the
      pulmonary system. While this approach can alleviate the demand for transplant
      through long-term biventricular support, it uncovers a new challenge with respect
      to controller strategies for these dual device support systems. This study
      compares the preload sensitivity of rotary, dual device biventricular assistance
      controllers in light of their ability to adjust the flow rate according to
      physiological demand. A Frank-Starling-like flow controller which requires both
      inlet pressure and flow sensors is compared to pressure controllers which
      maintain atrial or inlet cannula pressures through the use of a single pressure
      sensor. It was found that cannula selection and the location of a pressure
      controller's single pressure sensor can be tailored to adjust the preload
      sensitivity. When located within the atria, this sensitivity is effectively
      infinite. Moving the sensor to the base of a 450-mm cannula, however, decreased
      the sensitivity to 0.22 (L/min)/mm Hg. This indicates the potential for simple
      and reliable VAD controllers with increased preload sensitivity without the need
      for complex controllers requiring an array of hemodynamic sensors.

PMID- 21955296
TI  - Design, synthesis, and structure-activity relationship studies of highly potent
      novel benzoxazinyl-oxazolidinone antibacterial agents.
AB  - A series of novel benzoxazinyl-oxazolidinones bearing nonaromatic heterocycle or
      aryl groups were designed and synthesized. Their in vitro and in vivo
      antibacterial activities were investigated. Most of the (3S, 3aS) biaryl
      benzoxazinyl-oxazolidinones exhibited potent activity against Gram-positive
      pathogens. SAR trends were observed; a pyridyl C ring was preferable to other 5-
      or 6-member aryl C rings, while fluorine substitution on the B ring generated
      derivatives with reduced activity. Various substituent group positions on the
      pyridyl ring were also evaluated. The resulting compounds displayed excellent
      activity against linezolid-resistant strains. Compound 45 exhibited excellent in
      vitro activity, with a MIC value of 0.25-0.5 MUg/mL against MRSA and an activity
      against linezolid-resistant strains of 8-16-fold higher potency than linezolid.
      In a MRSA systemic infection model, compound 45 displayed an ED(50) < 5.0 mg/kg,
      a potency that is nearly 3-fold better than that of linezolid. This compound also
      showed excellent pharmacokinetic profiles, with a half-life of more than 5 h as
      well as an oral bioavailability of 81% in rats.

PMID- 21955297
TI  - Similarities and differences of hyperbaric oxygen and medical ozone applications.
AB  - Hyperbaric oxygen (HBO) treatment is based on the principle of having the patient
      breath 100% oxygen in an environment above atmospheric pressure. Ozone (O(3)) is
      a colourless gas with a specific odour and consists of three oxygen atoms. The
      classical scientific understanding is that the world has become a place suitable
      for life for aerobic organisms with the increasing oxygen in the atmosphere
      billions of years ago. The formation of ozone after oxygen has then protected
      aerobic creatures from harmful rays. We now use these two gases for treatment
      purposes. It is noteworthy that the oxygen and ozone molecules that are formed by
      the same atom in different numbers are used for similar medical indications. We
      will try to emphasize the similarities and differences of HBO and medical ozone
      applications in this article.

PMID- 21955298
TI  - Human neurocysticercosis: in vivo expansion of peripheral regulatory T cells and
      their recruitment in the central nervous system.
AB  - Human neurocysticercosis (NC) is caused by Taenia solium larvae lodged in the
      central nervous system. Most cases occur with no, or mild, neurological symptoms.
      However, in some patients, neuroinflammation is exacerbated, leading to severe
      forms of the disease. Considering the critical role of regulatory T cells (Tregs)
      in balancing inflammation in chronic diseases, their participation in restraining
      the inflammatory response in NC was explored in the present study. The frequency
      of Tregs and their relationship with the level of the proliferative response, the
      level of activated lymphocytes, and the cytokines expressed were determined in
      severe NC patients compared with those from healthy donors. Significantly
      increased peripheral Tregs (CD4(+)CD25(high) and CD4(+)CD25(high)FoxP3(+),
      CD4(+)CD25(high)CTLA4(+), and CD4(+)CD25(high) IL10(+)) and a significant
      decrease in activated (CD38(+) and CD69(+)) T cells were observed in 19 NC
      patients versus 10 healthy subjects. Significantly increased Tregs in NC are
      accompanied by a depressed specific, and non-specific, lymphocyte proliferative
      response, and they negatively correlate with activated CD4(+)CD69(+) lymphocytes.
      Treg frequencies were also determined in cerebral spinal fluid for 8 of the 19 NC
      patients. A positive significant correlation between peripheral and local Tregs
      was observed. Here, we report for the first time data that support the possible
      contribution of local and systemic Tregs in limiting neuroinflammation in NC.

PMID- 21955299
TI  - Fine needle aspiration cytology diagnosis of extramedullary haematopoiesis
      presenting as a pre-sacral mass: a pitfall avoided.

PMID- 21955300
TI  - Sentinel symptoms in patients with unexplained cardiac arrest: from the cardiac
      arrest survivors with preserved ejection fraction registry (CASPER).
AB  - BACKGROUND: Warning symptoms may provide an opportunity to diagnose genetic
      disorders leading to preventative therapy. We explored the symptom history of
      patients with apparently unexplained cardiac arrest to determine the frequency of
      sentinel symptoms. METHODS: Patients with apparently unexplained cardiac arrest
      and no evident cardiac disease underwent systematic clinical evaluation. Patients
      and first-degree relatives were interviewed to determine the presence of cardiac
      symptoms, and those with syncope underwent 2 structured Calgary Syncope Score
      questionnaires to determine the probable mechanism of syncope. RESULTS: One
      hundred consecutive cardiac arrest patients (age 43.0 +/- 13.4 years, 60% male)
      and 63 first-degree relatives (age 37.6 +/- 16.3 years, 54% female) were
      enrolled. Previous cardiac symptoms were present in 69% of cardiac arrest
      patients compared to 43% of family members (P = 0.001). Prior syncope was present
      in 26% of cardiac arrest patients, compared to 22% of family members (P = 0.59).
      Twenty-four of 25 cardiac arrest patients who completed the syncope
      questionnaires had a syncope versus seizure score <1 favoring syncope. The area
      under the receiver operator curve (ROC) for the syncope mechanism score was 0.79
      for identifying patients with subsequent cardiac arrest (95% CI, 0.6328-0.9395, P
      = 0.004). A score of <=-2 had a sensitivity of 68% and specificity of 85%. Thirty
      percent of patients with a proven genetic cause had preceding syncope versus 19%
      in patients with noninherited or idiopathic causes (P = 0.032). CONCLUSIONS:
      Syncope that may represent a sentinel event is present in a modest proportion of
      patients and family members, and is often suggestive of an arrhythmia.

PMID- 21955301
TI  - The consequences of mating over a range of parental genetic similarity in a
      selfing allopolyploid plant species.
AB  - In diploids, F(1)  offspring performance is expected to increase with increasing
      genetic dissimilarity between the parents until an optimum is reached because
      outbreeding mitigates inbreeding depression and maximizes heterosis. However,
      many flowering plant species are derived through allopolyploidization, i.e.
      interspecific hybridization with genome doubling. This mode of plant speciation
      can be expected to considerably alter the consequences of inbreeding and
      outbreeding. We investigated the F1 fitness consequences of mating over a range
      of (genetic) distances in the allohexaploid plant species Geum urbanum. Offspring
      was raised under controlled conditions (632 plants). The performance of
      outcrossed progeny was not significantly better than that of their selfed half
      siblings and did not increase with parental genetic dissimilarity (0-0.83). Our
      findings support low, if any, inbreeding depression and heterosis. We attribute
      this to the peculiar state of quasi-permanent heterozygosity in allopolyploids
      and frequent selfing.

PMID- 21955302
TI  - Fatigue resistance of acrylic resin denture base material reinforced with E-glass
      fibres.
AB  - OBJECTIVE: The purpose of the study was to determine the effect of different
      forms and concentrations (2.5, 3, 4, 5% by volume) of glass fibres (chopped
      strand mat, continuous and woven) on fatigue resistance of acrylic denture base
      resin. MATERIAL AND METHODS: The fatigue resistance was measured by applying
      repeated three-point bending deflection to the specimens, the cycle frequency of
      1.05 g and magnitude of deflection of 2.0 mm. The number of loading cycles needed
      to cause a fracture in the test specimen was considered the fatigue resistance of
      the specimen. RESULTS: The results of this study revealed that the addition of
      three different glass fibre forms at all concentrations to acrylic resin did not
      produce a statistically significant increase in the fatigue resistance (p >=
      0.05). This study also revealed that there were significant differences (p <
      0.05) between glass fibres forms used concerning the effects on the fatigue
      resistance. CONCLUSION: This study showed that the woven glass fibres had a
      definite superiority over the chopped fibres and the continuous fibres in regard
      to the fatigue resistance of the acrylic denture base resin.

PMID- 21955303
TI  - The gene expression landscape of thermogenic skunk cabbage suggests critical
      roles for mitochondrial and vacuolar metabolic pathways in the regulation of
      thermogenesis.
AB  - Floral thermogenesis has been described in several plant species. Because of the
      lack of comprehensive gene expression profiles in thermogenic plants, the
      molecular mechanisms by which floral thermogenesis is regulated remain to be
      established. We examined the gene expression landscape of skunk cabbage
      (Symplocarpus renifolius) during thermogenic and post-thermogenic stages and
      identified expressed sequence tags from different developmental stages of the
      inflorescences using super serial analysis of gene expression (SuperSAGE). In
      depth analysis suggested that cellular respiration and mitochondrial functions
      are significantly enhanced during the thermogenic stage. In contrast, genes
      involved in stress responses and protein degradation were significantly up
      regulated during post-thermogenic stages. Quantitative comparisons indicated that
      the expression levels of genes involved in cellular respiration were higher in
      thermogenic spadices than in Arabidopsis inflorescences. Thermogenesis-associated
      genes seemed to be expressed abundantly in the peripheral tissues of the spadix.
      Our results suggest that cellular respiration and mitochondrial metabolism play
      key roles in heat production during floral thermogenesis. On the other hand,
      vacuolar cysteine protease and other degradative enzymes seem to accelerate
      senescence and terminate thermogenesis in the post-thermogenic stage.

PMID- 21955305
TI  - Self-administered MDMA produces dose- and time-dependent serotonin deficits in
      the rat brain.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA) use and abuse have been increasing
      worldwide. Of concern, exposure to high doses of MDMA decreases several markers
      of serotonin (5HT) neurotransmission and produces deficits in tissue levels of
      5HT. Studies in laboratory animals have been conducted primarily following large
      doses (20.0-80.0 mg/kg) of experimenter-administered MDMA, but it is unclear
      whether similar persistent deficits in tissue 5HT levels are produced following
      self-administration. In this study, tissue levels of 5HT in the frontal cortex,
      striatum and hippocampus were measured following different levels of self
      administered MDMA. For both groups, responding was initially reinforced by an
      infusion of 1.0 mg/kg/infusion MDMA. The dose was reduced to 0.5 mg/kg/infusion
      once 90 infusions had been self-administered. For the two groups, testing
      continued until either a total of 165 or 315 mg/kg had been self-administered.
      Assays were conducted either 2 or 10 weeks following the last self-administration
      session. The lower dose exposure regimen failed to significantly decrease 5HT
      levels in any brain region. The higher dose exposure, however, decreased 5HT
      levels by 30-35% in all three brain regions 2 weeks, but not 10 weeks, following
      self-administration. Thus, MDMA self-administration produced dose- and time
      dependent deficits in tissue levels of 5HT, suggesting that similar deficits
      would be produced in humans who use and abuse the drug.

PMID- 21955304
TI  - Altered fibrin clot properties in patients with retinal vein occlusion.

PMID- 21955306
TI  - An integrative view on the carotid artery alterations in metabolic syndrome.
AB  - BACKGROUNDS: Metabolic syndrome (MetS) is a multiple risk factor paradigm widely
      considered in risk management. We aimed to investigate carotid artery alterations
      in MetS and the underlying risk factors. MATERIALS AND METHODS: A total of 400
      Chinese subjects were recruited, divided into control (n = 200) and MetS (n =
      200) groups. Clinical and laboratory characteristics were collected. All subjects
      underwent carotid ultrasonography. RESULTS: Cardiovascular risk profiles were
      worse in the MetS than control group (all P < 0.05). After adjusting for MetS and
      age, the MetS group showed significantly increased mean intima-media thickness
      (IMT(mean)) and significantly impaired carotid elastic properties (all P < 0.05),
      as compared to control group. Waist circumference (WC) was positively correlated
      with IMT(mean) (r = 0.130, P = 0.038), systolic carotid diameter (r = 0.139, P =
      0.026) and diastolic carotid diameter (r = 0.168, P = 0.007). systolic blood
      pressure (SBP) and diastolic blood pressure were positively correlated with
      IMT(mean) (r = 0.201, P = 0.004; r = 0.168, P = 0.008, respectively), but
      negatively with arterial compliance coefficient (r = -0.421, P < 0.001; r = 
      0.230, P < 0.001, respectively). Serum level of high-density lipoprotein (HDL)
      negatively correlated with IMT(mean) (r = -0.195, P = 0.002). Plaque index was
      positively correlated with fasting blood glucose (r = 0.205, P = 0.001) after
      adjusting for the other risk factors. Significantly impaired carotid elastic
      properties (all P < 0.05) independently correlated with IMT(mean) . Furthermore,
      age (beta = 0.255, P < 0.001), SBP (beta = 0.224, P < 0.001), WC (beta = 0.202, P
      < 0.001) and high-density lipoprotein cholesterol (HDL-C) (beta = -0.163, P =
      0.001) were independently associated with IMT(mean). CONCLUSION: Carotid
      alterations consequent upon MetS ultimately developed subclinical and clinical
      atherosclerosis, the underlying risk factors for which were abdominal obesity,
      hypertension, ageing and low level of HDL-C.

PMID- 21955307
TI  - Beckwith-Wiedemann syndrome with placental chorangioma due to H19-differentially
      methylated region hypermethylation: a case report.
AB  - Beckwith-Wiedemann syndrome (BWS) is a common overgrowth syndrome that involves
      abdominal wall defects, macroglossia, and gigantism. It is sometimes complicated
      by placental tumor and polyhydramnios. We report a case of BWS, prenatally
      diagnosed with ultrasonography. A large and well-circumscribed tumor also existed
      on the fetal surface of the placenta, which was histologically diagnosed as
      chorangioma after delivery. Polyhydramnios was obvious and the fetal heart
      enlarged progressively during pregnancy. Because the biophysical profiling score
      dropped to 4 points at 33 weeks of gestation, we carried out cesarean section. By
      epigenetic analysis, H19-differentially methylated region hypermethylation was
      observed in the placental tumor, normal placental tissue, and cord blood
      mononuclear cells. This is the first report of BWS with placental tumor due to
      H19-differentially methylated region hypermethylation.

PMID- 21955308
TI  - Current pattern of cleft lip and palate deformities in Lagos, Nigeria.
AB  - OBJECTIVE: To evaluate the current pattern of cleft lip and/or palate deformities
      in Lagos, Nigeria. Design : Descriptive epidemiology. SETTING: Statewide survey
      of patients. PARTICIPANTS/METHODS: All patients with cleft lip and palate
      deformities that were seen during a screening program for individuals with
      orofacial deformities in Lagos, Nigeria, between June 2006 and May 2008
      participated in this study. Demographic data were collected and physical
      examinations carried out. Cleft lip and/or palate deformities were classified
      using the Kernahan classification for common cases and the Tessier classification
      for the atypical cleft defects. RESULTS: A total of 225 patients were enrolled
      and completed the study. Cleft lip and palate was the most common presentation
      and was found in nearly 45% of the patients. Cleft lip was found in 61 (27%)
      patients. Twenty patients (8.89%) with different types of rare orofacial cleft
      deformities were seen. Cleft lip with or without cleft alveolus deformities
      occurred more commonly among males; whereas, cleft palate was more common among
      females. Cleft lip and/or palate occurred more frequently among males. Cleft lip
      with or without cleft alveolus was found predominantly on the left side.
      CONCLUSIONS: The pattern of cleft lip and/or palate deformities in Lagos,
      Nigeria, is different from those of other parts of Nigeria in some aspects. The
      proportion and varieties of atypical orofacial deformities in the study are
      striking. The prevalence of cleft lip and/or palate deformities in the study was
      2.25 per 100,000. There may be an association between the prevalence of atypical
      deformities and the high level of environmental pollutants in the Lagos area.

PMID- 21955309
TI  - Eosinophils as a clue to the diagnosis of microcystic adnexal carcinoma.

PMID- 21955311
TI  - AFX: what we now know.

PMID- 21955312
TI  - Myopericytoma and arterial intimal thickening: the relationship between
      myopericytes and myointimal cells.
AB  - BACKGROUND: Myopericytomas with intravascular growth have been reported and have
      been occasionally documented as intraarterial. In a retrospective study, we
      assessed intraarterial growth in myopericytomas, co-existence with arterial
      intimal thickening (IT) and the relationship between the two. METHODS: This
      retrospective study was undertaken using 11 myopericytomas evaluated in serial
      microscopical sections. The results in light microscopy, electron microscopy and
      immunohistochemistry [including alpha-smooth muscle actin (SMA), desmin and h
      caldesmon] were evaluated. RESULTS: In four myopericytomas, we found
      intraarterial growth, with large areas of disrupted arterial wall and attachment
      of veins and venules, exhibiting angiogenic phenomena. Arterial IT was present
      and partially incorporated within the tumor (simulating medium-sized vessels).
      The neointimal (myointimal) cells shared morphological and immunohistochemical
      phenotype with the myopericytoma myoid cells, including alpha-SMA positivity and
      desmin negativity. Four of the remaining myopericytomas showed structures similar
      to arterial IT within the tumor. CONCLUSIONS: The findings shown here, including
      the association between myopericytomas and arterial IT, the incorporation of the
      latter into the tumor and the similar phenotype of their respective myoid and
      myointimal cells, support a close relationship between these processes.
      Histogenically, the pericytes of the penetrating neovasculature originating from
      the attached venules and veins may contribute to both lesions.

PMID- 21955313
TI  - Expression of laminin-5 gamma2 chain in cutaneous pseudocarcinomatous
      hyperplasia.
AB  - BACKGROUND: Since the use of laminin-5 as a marker of invasiveness has been
      proposed by several authors, our objective was to compare the expression of this
      protein in pseudocarcinomatous hyperplasia and squamous cell carcinoma (SCC).
      METHODS: Sixty-four paraffin-embedded skin biopsy samples with diagnosis of
      epidermal hyperplasia (non-pseudocarcinomatous), pseudocarcinomatous hyperplasia,
      actinic keratosis/carcinoma in situ, microinvasive and frankly invasive SCC were
      obtained for immunohistochemical study. RESULTS: Adjacent normal epithelium and
      epidermal hyperplasia (non-pseudocarcinomatous) showed no staining. In
      pseudocarcinomatous hyperplasia, laminin-5 was positive, at least focally, in 14
      of 16 (87.5%) samples and was concentrated in peripheral cells of elongated rete
      pegs and in migrating cells in dermis. In samples of microinvasive carcinoma (n =
      7), the expression was observed in all cases and was concentrated in the leading
      edge of the tumor. All cases (n = 21) of frankly invasive SCC showed cells
      expressing laminin-5, at least focally. Well-differentiated areas of the tumor
      presented a pattern of expression in peripheral cells of tumor nests while a
      diffuse pattern of expression was observed in less differentiated areas.
      CONCLUSION: We showed that cytoplasmic laminin-5 expression should not be used as
      a criterion of malignancy and is not useful in distinguishing pseudocarcinomatous
      hyperplasia from microinvasive and well-differentiated SCC.

PMID- 21955314
TI  - Hypertrophic lupus erythematosus: the diagnostic utility of CD123 staining.
AB  - CD123-positive plasmacytoid dendrocytes are prominent in the infiltrate of
      discoid lupus erythematosus (LE). We hypothesized that these cells would also be
      present in hypertrophic LE and would aid in the histopathologic distinction from
      squamous cell carcinoma (SCC) and hypertrophic actinic keratosis (AK). Five cases
      of hypertrophic LE and 10 cases each of SCC and hypertrophic AK were stained with
      CD123. A heavy band of CD123-positive cells was present at the epidermal-dermal
      junction in all cases of hypertrophic LE, and only single or rare scattered
      clusters of CD123-positive cells were seen in SCC and actinic keratoses. The
      pattern of CD123 staining can be a useful feature to distinguish hypertrophic LE
      from SCC and hypertrophic AK.

PMID- 21955315
TI  - Eccrine hidradenitis sine neutrophils: a toxic response to chemotherapy.
AB  - We present a case of hidradenitis occurring in a patient after chemotherapy for
      acute myeloid leukemia (AML) in the setting of profound neutropenia. Neutrophilic
      eccrine hidradenitis (NEH) presents as tender erythematous papules and plaques
      and is often associated with chemotherapy for AML. NEH is postulated to be due to
      toxic injury to the sweat glands followed by neutrophilic inflammation.
      Alternatively, some hypothesize that NEH represents a primary neutrophilic
      process. Our patient's clinical presentation was similar to previously reported
      cases of NEH; however, degenerative changes of the sweat ducts were noted on
      microscopy without neutrophilic inflammation. She had fewer than 0.01 thousand
      neutrophils per microliter for 4 days preceding the biopsy. At the same time, a
      separate area of superficial skin infection developed because of Staphylococcus
      epidermidis and also lacked neutrophilic inflammation. The similar clinical
      course and shared histopathologic features between our case and NEH argue that
      neutrophils are a secondary response to a toxic effect rather than the primary
      effector in NEH. Neutrophil-poor variants of hidradenitis, both infectious and
      due to drug toxicity, should be considered diagnostically in neutropenic
      patients.

PMID- 21955318
TI  - Photo- and electrochemical redox behavior of cyclometalated Ru(II) complexes
      having a 3-phenylbenzo[b][1,6]naphthyridine ligand.
AB  - Cyclometalated Ru(II) complexes having a 3-phenylbenzo[b][1,6]naphthyridine
      (phbn) ligand have been synthesized and characterized by spectroscopic methods.
      The photo- and electrochemical redox behavior of the complexes are demonstrated.
      Complex [Ru(phbn)(bpy)(2)]PF(6) ([1]PF(6)) readily undergoes proton coupled two
      electron reduction by chemical, electrochemical, and photochemical methods to
      generate [Ru(phbnHH)(bpy)(2)]PF(6) ([1HH]PF(6)). The photochemical oxidation of
      [1HH]PF(6) was also observed in presence of p-chloranil.

PMID- 21955317
TI  - Gastrointestinal adverse effects of varenicline at maintenance dose: a meta
      analysis.
AB  - BACKGROUND: Tobacco smoking remains the leading modifiable health hazard and
      varenicline is amongst the most popular pharmacological options for smoking
      cessation. The purpose of this study is to critically evaluate the extent of
      gastrointestinal adverse effects of varenicline when used at maintenance dose (1
      mg twice a day) for smoking cessation. METHODS: We conducted a meta-analysis of
      randomised controlled trials published in PUBMED and EMBASE according to the
      PRISMA guidelines. Selected studies satisfied the following criteria: (i)
      duration of at least 6 weeks, (ii) titrated dose of varenicline for 7 days then a
      maintenance dose of 1 mg twice-per-day, (iii) randomized placebo-controlled
      design, (iv) extractable data on adverse event - nausea, constipation or
      flatulence. Data was synthesized into pooled odd ratios (OR) basing on random
      effects model. Quality of studies was also rated as per Cochrane risk-of-bias
      assessment. Number need to harm (NNH) was calculated for each adverse effect.
      RESULTS: 98 potentially relevant studies were identified, 12 of which met the
      final inclusion criteria (n = 5114). All 12 studies reported adverse events on
      nausea, which led to an OR of 4.45 (95% CI = 3.79-5.23, p < 0.001; I(2) = 0.06%,
      CI = 0%-58.34%) and a NNH of 5. Eight studies (n = 3539) contain data on
      constipation pooled into an OR of 2.45 (95% CI = 1.61-3.72, p < 0.001; I(2) =
      34.09%, CI = 0%-70.81%) with a NNH of 24. Finally, five studies (n = 2516)
      reported adverse events of flatulence, which pooled an OR of 1.74 (95% CI = 1.23
      2.48, p = 0.002; I(2) = 0%, CI = 0%- 79.2%) with a NNH of 35. CONCLUSIONS: Use of
      varenicline at maintenance dose of 1 mg twice a day for longer than 6 weeks is
      associated with adverse gastrointestinal effects. In realistic terms, for every 5
      treated subjects, there will be an event of nausea, and for every 24 and 35
      treated subjects, we will expect an event of constipation and flatulence
      respectively. Family physicians should counsel patients of such risks accordingly
      during their maintenance therapy with varenicline.

PMID- 21955319
TI  - Respiratory viruses in children with cystic fibrosis: viral detection and
      clinical findings.
AB  - BACKGROUND: Viral detection from different respiratory sample types in children
      with cystic fibrosis (CF) is facilitated by available molecular methods, but
      optimum sampling strategies have not been identified. In addition, associations
      between viral detection and respiratory symptoms are not well described.
      OBJECTIVES: Study goals were to compare molecular detection of viruses from
      concurrent upper airway and sputum samples in children with CF and to describe
      relative frequency of respiratory viral infections and identify potential
      clinical associations. METHODS: We conducted a 2-year prospective surveillance
      study in 44 children with CF aged 6-18 years. Upper airway and sputum samples
      were collected quarterly and during pulmonary exacerbations and tested for
      respiratory syncytial virus (RSV), influenza viruses, parainfluenza viruses types
      1-4, human metapneumovirus, coronaviruses, rhinoviruses, and adenoviruses.
      Physical exams and symptom surveys were used to identify respiratory signs and
      symptoms. RESULTS: Upper airway samples were collected at 359 visits; concordance
      of PCR-based viral detection was examined in a subset of paired upper airway and
      sputum samples from 21 participants at 92 visits. Rhinovirus was the most
      commonly detected virus (23.1% overall), and rhinovirus detection was the same
      for both sample types (21.7% each). Sensitivity and specificity for the detection
      of rhinovirus in sputum relative to upper airway sampling were 70% and 91.7%,
      respectively. Respiratory symptoms associated with rhinovirus detection included
      increased cough, increased nasal congestion, increased sputum production, and
      wheezing. CONCLUSIONS: A relatively high frequency of rhinovirus detection was
      observed by either upper airway or sputum samples, and clinical findings suggest
      a significant-associated symptom burden.

PMID- 21955320
TI  - A new 'dual' in the crown for electrochemistry.

PMID- 21955321
TI  - Visualization of co-localization in Abeta42-administered neuroblastoma cells
      reveals lysosome damage and autophagosome accumulation related to cell death.
AB  - Abeta42 [amyloid-beta peptide-(1-42)] plays a central role in Alzheimer's disease
      and is known to have a detrimental effect on neuronal cell function and survival
      when assembled into an oligomeric form. In the present study we show that
      administration of freshly prepared Abeta42 oligomers to a neuroblastoma (SH-SY5Y)
      cell line results in a reduction in survival, and that Abeta42 enters the cells
      prior to cell death. Immunoconfocal and immunogold electron microscopy reveal the
      path of the Abeta42 with time through the endosomal system and shows that it
      accumulates in lysosomes. A 24 h incubation with Abeta results in cells that have
      damaged lysosomes showing signs of enzyme leakage, accumulate autophagic vacuoles
      and exhibit severely disrupted nuclei. Endogenous Abeta is evident in the cells
      and the results of the present study suggest that the addition of Abeta oligomers
      disrupts a crucial balance in Abeta conformation and concentration inside
      neuronal cells, resulting in catastrophic effects on cellular function and,
      ultimately, in cell death.

PMID- 21955322
TI  - Thermal comfort and gender: a literature review.
AB  - This review examines scientific literature on the effect of gender on indoor
      thermal comfort. Gender differences have been generally considered to be small
      and insignificant but this review shows that a growing number of studies have
      found significant differences in thermal comfort between the genders. Clearly
      more than half of the laboratory and field studies have found that females
      express more dissatisfaction than males in the same thermal environments. Very
      few studies have found males to be more dissatisfied than females. A meta
      analysis shows that females are more likely than males to express thermal
      dissatisfaction (ratio: 1.74, 95% confidence interval: 1.61-1.89). However, most
      studies found no significant difference in neutral temperatures between the
      genders. Females are more sensitive than males to a deviation from an optimal
      temperature and express more dissatisfaction, especially in cooler conditions.
      PRACTICAL IMPLICATIONS: We should no longer neglect the more rigorous
      requirements that females have for indoor thermal environments. Gender
      differences indicate that females have, on average, a greater need for individual
      temperature control and adaptive actions than males. The results of this review
      suggest that females should primarily be used as subjects when examining indoor
      thermal comfort requirements, as if females are satisfied it is highly probable
      that males are also satisfied.

PMID- 21955324
TI  - Cytokine analysis in a patient with relapsing Kikuchi-Fujimoto disease.

PMID- 21955325
TI  - Reorganization energy for internal electron transfer in multicopper oxidases.
AB  - We have calculated the reorganization energy for the intramolecular electron
      transfer between the reduced type 1 copper site and the peroxy intermediate of
      the trinuclear cluster in the multicopper oxidase CueO. The calculations are
      performed at the combined quantum mechanics and molecular mechanics (QM/MM)
      level, based on molecular dynamics simulations with tailored potentials for the
      two copper sites. We obtain a reorganization energy of 91-133 kJ/mol, depending
      on the theoretical treatment. The two Cu sites contribute by 12 and 22 kJ/mol to
      this energy, whereas the solvent contribution is 34 kJ/mol. The rest comes from
      the protein, involving small contributions from many residues. We have also
      estimated the energy difference between the two electron-transfer states and show
      that the reduction of the peroxy intermediate is exergonic by 43-87 kJ/mol,
      depending on the theoretical method. Both the solvent and the protein contribute
      to this energy difference, especially charged residues close to the two Cu sites.
      We compare these estimates with energies obtained from QM/MM optimizations and QM
      calculations in a vacuum and discuss differences between the results obtained at
      various levels of theory.

PMID- 21955323
TI  - Identification of MACC1 as a novel prognostic marker in hepatocellular carcinoma.
AB  - BACKGROUND: Metastasis-associated in colon cancer-1 (MACC1) is a newly identified
      gene that plays a role in colon cancer metastasis through upregulation of c-MET
      proto-oncogene (c-MET). However, the value of MACC1 as a potential biomarker for
      hepatocellular carcinoma (HCC) remains unknown. METHODS: MACC1 mRNA expression in
      128 HCC tissues was examined by quantitative polymerase chain reaction. To show
      the potential correlation of MACC1 and c-MET, c-MET was also analysed. RESULTS:
      MACC1 was more highly expressed in HCC than in non-HCC tissues (P = 0.009). High
      MACC1 expression was significantly increased in cases with high alpha fetoprotein
      (AFP) (P = 0.025). A positive correlation was found between MACC1 and c-MET mRNAs
      (r = 0.235, P = 0.009). Both univariate and multivariate analyses revealed that
      MACC1 expression was associated with overall survival (OS) and disease-free
      survival (DFS). Moreover, stratified analysis showed that tumour-node-metastasis
      (TNM) stage I patients with high MACC1 levels had shorter OS and DFS than those
      with low MACC1. CONCLUSIONS: MACC1 may identify low- and high-risk individuals
      with HCC and be a valuable indicator for stratifying the prognosis of TNM stage I
      patients. MACC1 may serve as a novel biomarker for HCC.

PMID- 21955326
TI  - Transcriptional responses of Burkholderia cenocepacia to polymyxin B in isogenic
      strains with diverse polymyxin B resistance phenotypes.
AB  - BACKGROUND: Burkholderia cenocepacia is a Gram-negative opportunistic pathogen
      displaying high resistance to antimicrobial peptides and polymyxins. We
      identified mechanisms of resistance by analyzing transcriptional changes to
      polymyxin B treatment in three isogenic B. cenocepacia strains with diverse
      polymyxin B resistance phenotypes: the polymyxin B-resistant parental strain K56
      2, a polymyxin B-sensitive K56-2 mutant strain with heptoseless
      lipopolysaccharide (LPS) (RSF34), and a derivative of RSF34 (RSF34 4000B)
      isolated through multiple rounds of selection in polymyxin B that despite having
      a heptoseless LPS is highly polymyxin B-resistant. RESULTS: A heptoseless LPS
      mutant of B. cenocepacia was passaged through multiple rounds of selection to
      regain high levels of polymyxin B-resistance. This process resulted in various
      phenotypic changes in the isolate that could contribute to polymyxin B resistance
      and are consistent with LPS-independent changes in the outer membrane. The
      transcriptional response of three B. cenocepacia strains to subinhibitory
      concentrations of polymyxin B was analyzed using microarray analysis and
      validated by quantitative Real Time-PCR. There were numerous baseline changes in
      expression between the three strains in the absence of polymyxin B. In both K56-2
      and RSF34, similar transcriptional changes upon treatment with polymyxin B were
      found and included upregulation of various genes that may be involved in
      polymyxin B resistance and downregulation of genes required for the synthesis and
      operation of flagella. This last result was validated phenotypically as both
      swimming and swarming motility were impaired in the presence of polymyxin B.
      RSF34 4000B had altered the expression in a larger number of genes upon treatment
      with polymyxin B than either K56-2 or RSF34, but the relative fold-changes in
      expression were lower. CONCLUSIONS: It is possible to generate polymyxin B
      resistant isolates from polymyxin B-sensitive mutant strains of B. cenocepacia,
      likely due to the multifactorial nature of polymyxin B resistance of this
      bacterium. Microarray analysis showed that B. cenocepacia mounts multiple
      transcriptional responses following exposure to polymyxin B. Polymyxin B
      regulated genes identified in this study may be required for polymyxin B
      resistance, which must be tested experimentally. Exposure to polymyxin B also
      decreases expression of flagellar genes resulting in reduced swimming and
      swarming motility.

PMID- 21955328
TI  - Laser flow measurements in an idealized total cavopulmonary connection with
      mechanical circulatory assistance.
AB  - This study examined the interactive fluid dynamics between a cavopulmonary assist
      device and univentricular Fontan circulation. We conducted two-dimensional
      particle image velocimetry measurements on an idealized total cavopulmonary
      connection (TCPC) with an axial pump prototype intravascularly inserted into the
      inferior vena cava (IVC) and then in the IVC and the superior vena cava (SVC) for
      a dual-pump support case. The glass model of the TCPC consisted of rigid vessels
      having a diameter of 13.4 mm and a one-diameter vessel offset at the TCPC
      junction. Fluid velocity profiles were examined at a cardiac output of 3 L/min
      and SVC and IVC flow ratios of 30/70%, 40/60%, and 50/50% and pump rotational
      speeds from 3000 to 9000 rpm. In addition, cardiac outputs of 5 and 7 L/min were
      also examined. As compared to the flow profile with the pump present, the
      measured velocity field demonstrated the presence of rotational (i.e., out of
      plane) motion, which forced the higher-velocity regions toward the periphery of
      the vessel. As a result, few flow vortices were captured in the image plane
      downstream of the pump in the TCPC junction. However, the velocity profiles for
      all cases demonstrated the expected shunting preference of IVC flow toward the
      right pulmonary artery. Furthermore, the inclusion of the pump provided a
      pressure rise of 3 to 9 mm Hg, which would be sufficient to relieve systemic
      hypertension in Fontan patients with circulatory dysfunction.

PMID- 21955329
TI  - Research of masticatory function using hemiplegia simulator equipment.
AB  - BACKGROUND AND OBJECTIVE: Hemiplegic patients often exhibit a characteristic
      condition called Wernicke-Mann contracture. Therefore, the occlusal pattern in
      hemiplegic patients is considered to be adapted to stress because of this
      characteristic limb position. We created a sham Wernicke-Mann contracture in
      healthy individuals using hemiplegia simulator equipment and compared the
      functional occlusion in this position with that in the normal state to evaluate
      dynamic adaptive responses. METHODS: Wernicke-Mann contracture was simulated
      using a device to create sham hemiplegia (Manabi-tai, Hemiplegia Experiencing
      Set; Tokushu-iryo, Inc.). In addition to the measurement of the occlusal force
      using Dental Prescale((r)) and Occluzer((r)), the occlusion was evaluated using
      an electromyogram and stabilometer. RESULTS: There was a significant difference
      in the occlusal force between the normal state and during simulated hemiplegia.
      The surface electromyo-potential of the masseter muscle showed significantly
      higher values during simulated hemiplegia. It is significantly higher during
      simulated hemiplegia than in the normal state on the paralysed side, but not for
      the normal state on the non-paralysed side. The position and velocity vectors
      changed in the antero-posterior direction in the normal state but in the lateral
      direction during simulated hemiplegia. CONCLUSIONS: The hemiplegia simulator
      equipment is useful for research on hemiplegia, and that the occlusal balance is
      disturbed in the posture characteristic of hemiplegia.

PMID- 21955327
TI  - The metabolism and pharmacokinetics of phospho-sulindac (OXT-328) and the effect
      of difluoromethylornithine.
AB  - BACKGROUND AND PURPOSE: Phospho-sulindac (PS; OXT-328) prevents colon cancer in
      mice, especially when combined with difluoromethylornithine (DFMO). Here, we
      explored its metabolism and pharmacokinetics. EXPERIMENTAL APPROACH: PS
      metabolism was studied in cultured cells, liver microsomes and cytosol,
      intestinal microsomes and in mice. Pharmacokinetics and biodistribution of PS
      were studied in mice. KEY RESULTS: PS undergoes reduction and oxidation yielding
      PS sulphide and PS sulphone; is hydrolysed releasing sulindac, which generates
      sulindac sulphide (SSide) and sulindac sulphone (SSone), all of which are
      glucuronidated. Liver and intestinal microsomes metabolized PS extensively but
      cultured cells converted only 10% of it to PS sulphide and PS sulphone. In mice,
      oral PS is rapidly absorbed, metabolized and distributed to the blood and other
      tissues. PS survives only partially intact in blood; of its three major
      metabolites (sulindac, SSide and SSone), sulindac has the highest C(max) and
      SSone the highest t(1/2) ; their AUC(0-24h) are similar. Compared with
      conventional sulindac, PS generated more SSone but less SSide, which may
      contribute to the safety of PS. In the gastroduodenal wall of mice, 71% of PS was
      intact; sulindac, SSide and SSone together accounted for <30% of the total. This
      finding may explain the lack of gastrointestinal toxicity by PS. DFMO had no
      effect on PS metabolism but significantly reduced drug level in mouse plasma and
      other tissues. CONCLUSIONS AND IMPLICATIONS: Our findings establish the
      metabolism of PS define its pharmacokinetics and biodistribution, describe its
      interactions with DFMO and largely explain its gastrointestinal safety.

PMID- 21955331
TI  - Quality of medical devices and in vitro diagnostics in resource-limited settings.
AB  - The phenomenon of poor-quality medicines in resource-limited settings is well
      documented, and field observations reveal similar problems with medical devices
      (MDs) and in vitro diagnostics (IVDs). In scientific literature, however, there
      are only scarce reports and documents providing evidence of quality problems of
      MDs or IVDs in resource-limited settings. This discrepancy may be ascribed to (i)
      the poor regulatory oversight of MDs/IVDs in resource-limited settings, (ii) a
      general lack of awareness of the problem of poor-quality MDs/IVDs amongst the
      scientific community and decision-makers, and (iii) poor quality assurance in
      diagnostic laboratories in resource-poor settings, precluding tracing quality
      problems of IVDs from the other potential causes of diagnostic inaccuracy. The
      problem of poor-quality MDs/IVDs in resource-limited settings is a complex one to
      address. Firstly, operational definitions for substandard and counterfeit
      MDs/IVDs are required, as well as ad hoc field surveys, to ensure proper
      appraisal of the real extent of the problem. Investments are needed to reinforce
      the national regulatory oversights on MDs/IVDs in resource-limited settings, and
      to encourage a proactive and transparent exchange of information between Northern
      and Southern regulatory authorities. Industrialized countries can play a role by
      expanding and strengthening their regulatory oversight and quality labels to
      those MDs/IVDs that are frequently used in resource-poor settings. Hopefully, the
      combination of these measures will result in better protection of patients in
      resource-poor countries from the effects of being exposed to poor-quality MDs and
      IVDs.

PMID- 21955330
TI  - Description of a new species of bat-associated argasid tick (Acari: Argasidae)
      from Brazil.
AB  - A new species of argasid tick (Acari: Argasidae) is described from immature and
      adult specimens collected from several localities in Brazil. A complete
      morphological account is provided for all postembryonic life stages, i.e., larva,
      nymph, female, and male. Ornithodoros cavernicolous n. sp. is the 113(th) in the
      genus. Morphologically, the new species shares common features, e.g., presence of
      well-developed cheeks and legs with micromammillate cuticle, with other bat
      associated argasid ticks included in the subgenus Alectorobius. In particular,
      the new species is morphologically related to Ornithodoros azteci Matheson, with
      which it forms a species group. Phylogenetic analysis based on the 16S rRNA gene
      sequences supports the placement of the new species within a large clade that
      includes other New World bat-associated argasids. However, the new species seems
      to represent an independent lineage within the genus Ornithodoros.

PMID- 21955332
TI  - Guidelines for pregnancy: what's an acceptable risk, and how is the evidence
      (finally) shaping up?
AB  - ISSUES: The lack of consensus about whether low to moderate levels of prenatal
      alcohol exposure are a risk factor for fetal development has generated
      considerable debate about what advice policies and guidelines should provide.
      APPROACH: This paper reviews the evidence from systematic reviews and meta
      analyses examining the risk from low and moderate levels of prenatal alcohol
      exposure, along with the results of articles published 2009-2010, after the
      reviews. KEY FINDINGS: The reported significant effects from low levels of
      prenatal alcohol exposure are likely due to methodological issues such as
      confounding and/or misclassification of exposure or outcome and there is no
      strong research evidence of fetal effects from low levels of alcohol exposure.
      However, harm is well-documented with heavy exposure and moderate levels of
      exposure, 30-40 g per occasion and no more than 70 g per week, have been
      demonstrated to increase the risk of child behaviour problems. IMPLICATIONS: With
      such a small margin before there is increased risk to the fetus, it would be
      morally and ethically unacceptable for policies and guidelines to condone
      consumption of alcohol during pregnancy. Not all women will follow this advice
      and some women will inadvertently consume alcohol prior to pregnancy awareness
      requiring non-judgmental counselling and the provision of rational advice about
      the likelihood of risk to the fetus. CONCLUSIONS: The policy advice that 'the
      safest choice for pregnant women is to abstain from alcohol during pregnancy'
      should be maintained. However, the abstinence message needs to be presented in a
      balanced and rational manner to prevent unintended negative consequences.

PMID- 21955335
TI  - An experimental comparison of gene selection by Lasso and Dantzig selector for
      cancer classification.
AB  - Selecting a subset of genes with strong discriminative power is a very important
      step in classification problems based on gene expression data. Lasso and Dantzig
      selector are known to have automatic variable selection ability in linear
      regression analysis. This paper applies Lasso and Dantzig selector to select the
      most informative genes for representing the probability of an example being
      positive as a linear function of the gene expression data. The selected genes are
      further used to fit different classifiers for cancer classification. Comparative
      experiments were conducted on six publicly available cancer datasets, and the
      detailed comparison results show that in general, Lasso is more capable than
      Dantzig selector at selecting informative genes for cancer classification.

PMID- 21955333
TI  - 4-nitrobenzyloxycarbonyl derivatives of O(6)-benzylguanine as hypoxia-activated
      prodrug inhibitors of O(6)-alkylguanine-DNA alkyltransferase (AGT), which
      produces resistance to agents targeting the O-6 position of DNA guanine.
AB  - A series of 4-nitrobenzyloxycarbonyl prodrug derivatives of O(6)-benzylguanine
      (O(6)-BG), conceived as prodrugs of O(6)-BG, an inhibitor of the resistance
      protein O(6)-alkylguanine-DNA alkyltransferase (AGT), were synthesized and
      evaluated for their ability to undergo bioreductive activation by reductase
      enzymes under oxygen deficiency. Three agents of this class, 4-nitrobenzyl (6
      (benzyloxy)-9H-purin-2-yl)carbamate (1) and its monomethyl (2) and gem-dimethyl
      analogues (3), were tested for activation by reductase enzyme systems under
      oxygen deficient conditions. Compound 3, the most water-soluble of these agents,
      gave the highest yield of O(6)-BG following reduction of the nitro group trigger.
      Compound 3 was also evaluated for its ability to sensitize 1,2
      bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(methylamino)carbonyl]hydrazine
      (laromustine)-resistant DU145 human prostate carcinoma cells, which express high
      levels of AGT, to the cytotoxic effects of this agent under normoxic and oxygen
      deficient conditions. While 3 had little or no effect on laromustine cytotoxicity
      under aerobic conditions, significant enhancement occurred under oxygen
      deficiency, providing evidence for the preferential release of the AGT inhibitor
      O(6)-BG under hypoxia.

PMID- 21955336
TI  - Higher education versus higher learning for rural practice.

PMID- 21955337
TI  - President's message: what if somebody cared?

PMID- 21955338
TI  - Accuracy of the Broselow tape in estimating the weight of First Nations children.
AB  - INTRODUCTION: During resuscitation, the Broselow tape (BT) is the standard method
      of estimating pediatric weight based on body length. The First Nations population
      has a higher prevalence of obesity and experiences more injury than the non-First
      Nations population. The prevalence of obesity has raised the concern that the BT
      may not accurately estimate weight in this population. The purpose of this study
      was to validate the BT in 8 First Nations communities. METHODS: We performed a
      search of the electronic medical records of 2 community health centres that serve
      8 local First Nations communities. We searched for the most recent clinic visit
      during which height and weight had been recorded in the records of patients less
      than 10 years of age with a postal code indicating residence in a First Nations
      community. The patients' actual weight was compared with their BT weight
      estimates using the Bland-Altman method. The Spearman coefficient of rank and
      percentage error was also calculated. RESULTS: A total of 243 children were
      included in the study (119 girls, 124 boys). The mean age was 33.3 months (95%
      confidence interval [CI] 29.7 to 36.9), mean height was 91.8 cm (95% CI 89.0 to
      94.6), mean weight was 16.2 kg (95% CI 15.0 to 17.3)and mean BT weight was 14.0
      kg (95% CI 13.1 to 14.8). The Bland-Altman percent difference was 11.9% (95% CI 
      17.3% to 41.1%). The Spearman coefficient of rank correlation was 0.963 (p <
      0.001). The BT had a percentage error greater than 10% error 51.8% of the time,
      with 49.4% being underestimations. CONCLUSION: The BT was often not accurate at
      estimating the weight of children in 8 First Nations communities; it
      underestimated their weight almost half of the time.

PMID- 21955339
TI  - Delivering away from home: the perinatal experiences of First Nations women in
      northwestern Ontario.
AB  - INTRODUCTION: Our objective was to understand the perinatal knowledge and
      experiences of First Nations women from northwestern Ontario who travel away from
      their remote communities to give birth. METHODS: A systematic review of MEDLINE,
      HealthSTAR, HAPI, Embase, AMED, PsycINFO and CINAHL was undertaken using Medical
      Subject Headings and keywords focusing on Canadian Aboriginal (First Nations,
      Metis and Inuit) prenatal education and care, and maternal health literacy. This
      qualitative study using semistructured interviews was conducted in a rural
      hospital and prenatal clinic that serves First Nations women. Thirteen women from
      remote communities who had travelled to Sioux Lookout, Ont., to give birth
      participated in the study. RESULTS: We identified 5 other qualitative studies
      that explored the birthing experiences of Aboriginal women. The studies
      documented a negative experience for women who travelled to access intrapartum
      maternity care. While in Sioux Lookout to give birth, our participants also
      experienced loneliness and missed their families. They were open to the idea of a
      culturally appropriate doula program and visits in hospital by First Nations
      elders, but they were less interested in access to tele-visitation with family
      members back in their communities. We found that our participants received most
      of their prenatal information from family members. CONCLUSION: First Nations
      women who travel away from home to give birth often travel great cultural and
      geographic distances. Hospital-based maternity care programs for these women need
      to achieve a balance of clinical and cultural safety. Programs should be
      developed to lessen some of the negative consequences these women experience.

PMID- 21955340
TI  - The occasional teacher. Part 5: the learner in difficulty.

PMID- 21955341
TI  - Country cardiograms case 41.

PMID- 21955342
TI  - The rural care needs index: a potential tool for "have-not" communities.

PMID- 21955344
TI  - Rural medicine goes wild.

PMID- 21955346
TI  - Japanese Resident Physicians' Attitudes, knowledge, and Perceived Barriers on the
      Practice of Evidence Based Medicine: a Survey.
AB  - BACKGROUND: Evidence based medicine plays a crucial role as a tool that helps
      integrate research evidence into clinical practice. However, few reports have yet
      to examine its application in daily practice among resident physicians in Japan.
      The aim of this study was to assess the attitudes towards and knowledge of EBM
      among resident physicians in Japanese and determine perceived barriers to its
      use. FINDINGS: A cross-sectional, self-administered anonymous questionnaire was
      distributed to 60 resident staffs at Saga University Hospital in Japan.Forty
      residents completed and returned the questionnaire. Fifty four percent of
      respondents understood the basic terminology of EBM, 3% could explain this to
      others, and 41% indicated they would like to understand the terminology more.
      Thirteen percent admitted having a good understanding of EBM basic skills. Fifty
      respondents indicated having read EBM sources, but only 3% indicated that they
      use these sources in clinical decision making. The most prominent barriers of EBM
      application revealed in this study were insufficient time to access the sources,
      a lack of native language references, and insufficient basic EBM skills, but not
      scepticism about the EBM concept. CONCLUSIONS: In general, respondents positively
      welcomed EBM, and moderately understood and knew basic EBM skill; however,
      barriers in its application were shown to exist.

PMID- 21955347
TI  - Environmental and physiological controls on the carbon isotope composition of CO2
      respired by leaves and roots of a C3 woody legume (Prosopis velutina) and a C4
      perennial grass (Sporobolus wrightii).
AB  - Accurate estimates of the delta(13) C value of CO(2)  respired from roots
      (delta(13) C(R_root) ) and leaves (delta(13) C(R_leaf) ) are important for
      tracing and understanding changes in C fluxes at the ecosystem scale. Yet the
      mechanisms underlying temporal variation in these isotopic signals are not fully
      resolved. We measured delta(13) C(R_leaf) , delta(13) C(R_root) , and the
      delta(13) C values and concentrations of glucose and sucrose in leaves and roots
      in the C(4)  grass Sporobolus wrightii and the C(3)  tree Prosopis velutina in a
      savanna ecosystem in southeastern Arizona, USA. Night-time variation in delta(13)
      C(R_leaf)  of up to 4.6 +/- 0.60/00 in S. wrightii and 3.0 +/- 0.60/00 in P.
      velutina were correlated with shifts in leaf sucrose concentration, but not with
      changes in delta(13) C values of these respiratory substrates. Strong positive
      correlations between delta(13) C(R_root)  and root glucose delta(13) C values in
      P. velutina suggest large diel changes in delta(13) C(R_root)  (were up to
      3.90/00) influenced by short-term changes in delta(13) C of leaf-derived phloem
      C. No diel variation in delta(13) C(R_root)  was observed in S. wrightii. Our
      findings show that short-term changes in delta(13) C(R_leaf)  and delta(13)
      C(R_root)  were both related to substrate isotope composition and concentration.
      Changes in substrate limitation or demand for biosynthesis may largely control
      short-term variation in the delta(13) C of respired CO(2)  in these species.

PMID- 21955348
TI  - Developing and implementing an institute-wide data sharing policy.
AB  - The Wellcome Trust Sanger Institute has a strong reputation for prepublication
      data sharing as a result of its policy of rapid release of genome sequence data
      and particularly through its contribution to the Human Genome Project. The
      practicalities of broad data sharing remain largely uncharted, especially to
      cover the wide range of data types currently produced by genomic studies and to
      adequately address ethical issues. This paper describes the processes and
      challenges involved in implementing a data sharing policy on an institute-wide
      scale. This includes questions of governance, practical aspects of applying
      principles to diverse experimental contexts, building enabling systems and
      infrastructure, incentives and collaborative issues.

PMID- 21955349
TI  - Lethal effects of abamectin on the aquatic organisms Daphnia similis, Chironomus
      xanthus and Danio rerio.
AB  - Abamectin is used as an acaricide and insecticide for fruits, vegetables and
      ornamental plants, as well as a parasiticide for animals. One of the major
      problems of applying pesticides to crops is the likelihood of contaminating
      aquatic ecosystems by drift or runoff. Therefore, toxicity tests in the
      laboratory are important tools to predict the effects of chemical substances in
      aquatic ecosystems. The aim of this study was to assess the potential hazards of
      abamectin to the freshwater biota and consequently the possible losses of
      ecological services in contaminated water bodies. For this purpose, we identified
      the toxicity of abamectin on daphnids, insects and fish. Abamectin was highly
      toxic, with an EC(50) 48 h for Daphnia similis of 5.1 ng L(-1), LC(50) 96 h for
      Chironomus xanthus of 2.67 MUg L(-1) and LC(50) 48 h for Danio rerio of 33 MUg L(
      1).

PMID- 21955350
TI  - Sucralose - an ecotoxicological challenger?
AB  - The non-calorie sweetener sucralose - sucrose containing three chlorine atoms -
      is intensively sweet and has become a popular substitute for sugar. Its
      widespread use, exceptional stability in combination with high water solubility
      have thus resulted in contamination of recipient waters. Earlier studies on
      sucralose in aquatic organisms indicate low bioaccumulation potential and
      negligible acute/chronic toxicity, but the close structural resemblance with
      sucrose in combination with the importance of sugar in nature, warrant a more
      detailed ecotoxicological assessment. The aim of this investigation was therefore
      to study behavioural and physiological effects of sucralose in crustaceans. Our
      results show that both physiology and locomotion behaviour were affected by
      exposure to sucralose. In Daphnia magna, the behavioural response was manifested
      as altered swimming height and increased swimming speed, whereas in gammarids the
      time to reach food and shelter was prolonged. Regardless if these behavioural
      responses were initiated via traditional toxic mechanisms or stimulatory effects,
      they should be considered as a warning, since exposed organisms may diverge from
      normal behaviour, which ultimately can have ecological consequences.

PMID- 21955351
TI  - Validation and use of in vivo solid phase micro-extraction (SPME) for the
      detection of emerging contaminants in fish.
AB  - A variety of emerging chemicals of concern are released continuously to surface
      water through the municipal wastewater effluent discharges. The ability to
      rapidly determine bioaccumulation of these contaminants in exposed fish without
      sacrificing the animal (i.e. in vivo) would be of significant advantage to
      facilitate research, assessment and monitoring of their risk to the environment.
      In this study, an in vivo solid phase micro-extraction (SPME) approach was
      developed and applied to the measurement of a variety of emerging contaminants
      (carbamazepine, naproxen, diclofenac, gemfibrozil, bisphenol A, fluoxetine,
      ibuprofen and atrazine) in fish. Our results indicated in vivo SPME was a
      potential alternative extraction technique for quantitative determination of
      contaminants in lab exposures and as well after exposure to two municipal
      wastewater effluents (MWWE), with a major advantage over conventional techniques
      due to its ability to non-lethally sample tissues of living organisms.

PMID- 21955352
TI  - Plant uptake of pesticides and human health: dynamic modeling of residues in
      wheat and ingestion intake.
AB  - Human intake of pesticide residues from consumption of processed food plays an
      important role for evaluating current agricultural practice. We take advantage of
      latest developments in crop-specific plant uptake modeling and propose an
      innovative dynamic model to estimate pesticide residues in the wheat-environment
      system, dynamiCROP. We used this model to analyze uptake and translocation of
      pesticides in wheat after foliar spray application and subsequent intake
      fractions by humans. Based on the evolution of residues in edible parts of
      harvested wheat we predict that between 22 mg and 2.1 g per kg applied pesticide
      are taken in by humans via consumption of processed wheat products. Model results
      were compared with experimentally derived concentrations in wheat ears and with
      estimated intake via inhalation and ingestion caused by indirect emissions, i.e.
      the amount lost to the environment during pesticide application. Modeled and
      measured concentrations in wheat fitted very well and deviate from less than a
      factor 1.5 for chlorothalonil to a maximum factor 3 for tebuconazole. Main
      aspects influencing pesticide fate behavior are degradation half-life in plant
      and time between pesticide application and crop harvest, leading to variations in
      harvest fraction of at least three orders of magnitude. Food processing may
      further reduce residues by approximately 63%. Intake fractions from residues in
      sprayed wheat were up to four orders of magnitude higher than intake fractions
      estimated from indirect emissions, thereby demonstrating the importance of
      exposure from consumption of food crops after direct pesticide treatment.

PMID- 21955353
TI  - Derivation of predicted no effect concentrations (PNEC) for 2,4,6-trichlorophenol
      based on Chinese resident species.
AB  - 2,4,6-Trichlorophenol (2,4,6-TCP) is a common chemical intermediate and a by
      product of water chlorination and combustion processes, and is a priority
      pollutant of the aquatic environment in many countries. Although information on
      the toxicity of 2,4,6-TCP is available, there is a lack of information on the
      predicted no-effect concentration (PNEC) of 2,4,6-TCP, mainly due to the shortage
      of chronic and site-specific toxicity data. In the present study, acute and sub
      chronic toxicity of 2,4,6-TCP on six different resident Chinese aquatic species
      were determined. PNEC values were calculated and compared by use of two
      approaches: assessment factor (AF) and species sensitivity distribution (SSD).
      Values for acute toxicity ranged from 1.1 mg L(-1) (Plagiognathops microlepis) to
      42 mg L(-1) (Corbicula fluminea) and the sub-chronic no observed effect
      concentrations (NOECs) ranged from 0.05 mg L(-1) (Mylopharyngodon piceus) to 2.0
      mg L(-1) (C. fluminea). PNECs obtained by the assessment factor approach with
      acute (AF=1000, 0.001 mg L(-1)) or chronic (AF=10, 0.005 mg L(-1)) toxicity data
      were one order of magnitude less than those from SSD methods (0.057 mg L(-1)).
      PNEC values calculated using SSD methods with a 50% certainty for 2,4,6-TCP was
      less than those obtained by use of the USEPA recommend final chronic value (FCV)
      method (0.097 mg L(-1)) and the one obtained by use of the USEPA recommend acute
      to-chronic (ACR) methods (0.073 mg L(-1)). PNECs derived using AF methods were
      more protective and conservative than that derived using SSD methods.

PMID- 21955354
TI  - Transformation products and reaction kinetics of fragrances in advanced
      wastewater treatment with ozone.
AB  - The reaction of the fragrance compounds 4,6,6,7,8,8-hexamethyl-1,3,4,7
      tetrahydrocyclopenta[g]isochromene (HHCB), 1-(3,5,5,6,8,8-hexamethyl-6,7
      dihydronaphthalen-2-yl)ethanone (AHTN), 1-tert-butyl-3,5-dimethyl-2,4,6
      trinitrobenzene (musk xylene/MX), 1-(4-tert-butyl-2,6-dimethyl-3,5
      dinitrophenyl)ethanone (musk ketone/MK), and 1-(2,3,8,8-tetramethyl-1,3,4,5,6,7
      hexahydronaphthalen-2-yl)ethanone (OTNE) with ozone in tap water as well as waste
      water treatment plant (WWTP) effluents is described. Several transformation
      products are characterized by means of gas chromatography coupled to mass
      spectrometry. One transformation product (HHCB-Lactone) was confirmed by means of
      a true standard. Musk xylene and musk ketone do not react with ozone under the
      conditions used in this study. AHTN and HHCB reacted slowly to a multitude of
      transformation products, while OTNE reacted quickly to several stable
      transformation products. The reaction constants and half lives are used to
      predict removal efficiencies for full scale reactors.

PMID- 21955355
TI  - The presence of Bacillus thuringiensis (Bt) protein in earthworms Eisenia fetida
      has no deleterious effects on their growth and reproduction.
AB  - Earthworms Eisenia fetida, bred in substances with stover of two genetically
      engineered Bacillus thuringiensis (Bt) corns (5422Bt1 (Event Bt11) and 5422CBCL
      (MON810)) expressing Cry1Ab and their near-isogenic non-Bt corn (5422), were used
      to investigate the non-target effects of Bt corn on soil-dwelling organisms.
      Cry1Ab concentrations in substances, casts and guts of E. fetida were also
      investigated by Enzyme-linked immunosorbent assay (ELISA). More than 90%
      individuals of E. fetida survived over a period of 30 d, irrespective of whether
      they received Bt corn or non-Bt corn. Compared to 5422 treatments, significantly
      higher relative growth rate and more number of new offspring and cocoons of E.
      fetida were found in 5422Bt1 and 5422CBCL treatments. These results were unlikely
      to be directly caused by Cry1Ab released from Bt corns but rather by differences
      in other factors of plants such as plant components (soluble sugar, total organic
      carbon, total protein and available phosphorus of Bt corns were more than 5422).
      ELISA results indicated immunoreactive Cry1Ab was detectable in substances, and
      the casts, guts of E. fetida from Bt corns treatments, of which the highest
      levels were detected in substances under the corresponding experimental
      conditions. With the increase of treated time, a strong decline was observed in
      Cry1Ab from substances and casts of E. fetida, whereas Cry1Ab in guts of E.
      fetida from 5422Bt1 treatments gradually increased and that from 5422CBCL
      treatments increased between 14 and 30 d. Therefore, the presence of Cry1Ab in E.
      fetida had no deleterious effects on their growth and reproduction.

PMID- 21955357
TI  - Antidepressants and the developing nervous system.

PMID- 21955356
TI  - Multisite virological influenza surveillance in India: 2004-2008.
AB  - BACKGROUND: Influenza surveillance is important to identify circulating,
      emerging/reemerging strains and unusual epidemiological trends. With these
      objectives, a multisite human influenza surveillance network was initiated in
      India in 2004. METHODS: Epidemiologic data and throat swabs for laboratory
      testing were collected from patients with influenza-like illness (ILI) and severe
      acute respiratory infections (SARI). Virus isolation was carried out in Madin
      Darby canine kidney cells and strains identified by hemagglutination inhibition
      assay. Meteorological data were collected. RESULTS: From September 2004 to
      December 2008, 617 (4.43%) of 13928 cases yielded isolates: 27.8% were influenza
      A(H1N1), 29.8% were type A(H3N2), and 42.3% were type B. The yearly type and
      subtype distribution varied significantly from site to site. Peak influenza
      activity was observed from June to August in Delhi, Pune, and Kolkata and October
      to December in Chennai. Maximum influenza activity was seen during the rains in
      Delhi, Pune, Chennai, and Kolkata in correlation with virus isolations.
      Multivariate analysis of ILI cases showed chill/rigors, cough, fatigue, and ILI
      in family, correlated positively with isolation. Genetic analysis of Indian
      isolates revealed that viruses matched with vaccine strains by and large.
      Overlapping between circulating and vaccine component strains of consecutive
      years was also observed. CONCLUSIONS: Seasonal influenza A(H1N1), H3N2, and type
      B co-circulated in all regions without any particular pattern of movement of any
      subtype. Year-round limited influenza activity with peaks during rains was
      observed. Genetic drifts and varying seasonality in different parts of the
      country suggest that a staggered timing of vaccination may be appropriate for
      India.

PMID- 21955358
TI  - When do we need to perform laparotomy for benign uterine disease? Factors
      involved with conversion in vaginal hysterectomy.
AB  - AIM: To identify the preoperative risk factors affecting the conversion to
      laparotomy during vaginal hysterectomy (VH) for benign uterine conditions.
      MATERIAL AND METHODS: The charts were reviewed for all patients who underwent VH
      between 1 January 2003 and 31 December 2008 at Hallym University Hospital, Seoul.
      RESULTS: The rate of conversion to laparotomy was 3.7% (32 cases). Factors that
      were independently associated with the risk of conversion to laparotomy were
      found to be low parity (conversion 1.43 vs VH 1.92, P=0.021), previous abdominal
      surgery (conversion 0.71 vs, VH 0.26, P=0.012), pelvic adhesion (conversion 1.25
      vs VH 0.04, P=0.000), and large uterine weight (conversion 345.15g vs VH 222.38g,
      P=0.005). In the conversion group, the operative time was longer (conversion
      144.84min vs VH 77.67min, P=0.000), and estimated blood loss was also greater
      (conversion 656.25mL vs VH 358.47mL, P=0.00). Postoperative hemoglobin change
      (conversion 1.65g/dL vs VH 1.23g/dL, P=0.046) and transfusion rate were also
      greater in the conversion group (conversion 0.75 vs VH 0.01, P=0.001).
      CONCLUSION: VH is the main procedure for benign uterine disease and is
      successfully performed in most cases. But several factors, including low parity,
      previous abdominal surgery, pelvic adhesion and large uterine weight can affect
      the risk of conversion to laparotomy.

PMID- 21955359
TI  - The chemokine BRAK/CXCL14 regulates synaptic transmission in the adult mouse
      dentate gyrus stem cell niche.
AB  - The chemokine BRAK/CXCL14 is an ancient member of the chemokine family whose
      functions in the brain are completely unknown. We examined the distribution of
      CXCL14 in the nervous system during development and in the adult. Generally
      speaking, CXCL14 was not expressed in the nervous system prior to birth, but it
      was expressed in the developing whisker follicles (E14.5) and subsequently in the
      hair follicles and skin. Postnatally, CXCL14 was also highly expressed in many
      regions of the brain, including the cortex, basal ganglia, septum and
      hippocampus. CXCL14 was also highly expressed in the dorsal root ganglia. We
      observed that in the hippocampal dentate gyrus (DG) CXCL14 was expressed by
      GABAergic interneurons. We demonstrated that CXCL14 inhibited GABAergic
      transmission to nestin-EGFP-expressing neural stem/progenitor cells in the adult
      DG. CXCL14 inhibited both the tonic and phasic effects of synaptically released
      GABA. In contrast CXCL12 enhanced the effects of GABA at these same synapses.
      CXCL14 increased [Ca(2+)](i) in neural stem cells cultured from the postnatal
      brain indicating that they expressed the CXCL14 receptor. These observations are
      consistent with the view that CXCL12 and CXCL14 may normally act as positive and
      negative regulators of the effects of GABA in the adult DG stem cell niche.

PMID- 21955360
TI  - Development and validation of a self-rating scale for betel quid chewers based on
      a male-prisoner population in Taiwan: the Betel Quid Dependence Scale.
AB  - BACKGROUND: Betel quid is a substance that commonly used among male labor in
      Taiwan, and the dependence potential has been reported in some studies, but no
      instrument has been developed specifically to assess areca/betel quid dependence.
      OBJECTIVE: To develop a reliable and valid research instrument/screening tool for
      the measurement of betel quid dependence. METHODS: There were 223 male prisoners
      with a history of betel quid chewing behavior before they were incarcerated in
      Kaohsiung Prison enrolled in this study. The items of the Betel Quid Dependence
      Scale (BQDS) were developed by the authors and were designed referring to
      previous research findings and the diagnostic criteria of Substance Dependence in
      DSM-IV. RESULTS: The BQDS has high internal consistency (Cronbach's alpha=0.921),
      and a three-factor structure consisting of "physical and psychological urgent
      need," "increasing dose" and "maladaptive use," which accounted for 61.2% of the
      total variance. There were 94 (42.2%) male-prisoners who satisfied DSM-IV
      criteria for dependent use, and the receiver operating characteristic (ROC) curve
      showed that the BQDS had an optimal cut-off score of 4, the optimal sensitivity
      was 0.926 and the specificity was 0.977, with the predictive accuracy up to
      99.3%. CONCLUSIONS: The BQDS has good internal consistency and construct
      validity, and was proved to have optimal reliability and criterion validity in
      this special sample. Further investigation is suggested in different samples such
      as the general population or oral submucous fibrosis (OSF) patients to test the
      generalization of this instrument.

PMID- 21955361
TI  - "Ready, willing, and (not) able" to change: young adults' response to residential
      treatment.
AB  - BACKGROUND: Young adulthood represents a key developmental period for the onset
      of substance use disorder (SUD). While the number of young adults entering
      treatment has increased, little is known about the mechanisms of change and early
      recovery processes in this important clinical population. This study investigated
      during-treatment change in key therapeutic processes (psychological distress,
      motivation, self-efficacy, coping skills, and commitment to AA/NA), and tested
      their relation to outcome at 3 months post-treatment. METHODS: Young adults
      undergoing residential treatment (N=303; age 18-24; 26% female; 95% Caucasian)
      were enrolled in a naturalistic prospective study and assessed at intake, mid
      treatment, discharge, and 3 months following discharge. Repeated-measures and
      regression analyses modeled during-treatment change in process variables and
      impact on outcome. RESULTS: Statistically significant medium to large effect
      sizes were observed for changes in most processes during treatment, with the
      exception of motivation, which was high at treatment intake and underwent
      smaller, but still significant, change. In turn, these during-treatment changes
      all individually predicted 3-month abstinence to varying degrees, with self
      efficacy emerging as the sole predictor in a simultaneous regression.
      CONCLUSIONS: Findings help to clarify the mechanisms through which treatment
      confers recovery-related benefit among young adults. At treatment intake, high
      levels of abstinence motivation but lower coping, self-efficacy, and commitment
      to AA/NA, suggests many entering treatment may be "ready and willing" to change,
      but "unable" to do so without help. Treatment appears to work, in part, by
      helping to maintain motivation while conferring greater ability and confidence to
      enact such change.

PMID- 21955362
TI  - Tobacco, alcohol, cannabis and other illegal drug use among young adults: the
      socioeconomic context.
AB  - BACKGROUND: Low socioeconomic position predicts risk of substance abuse, yet few
      studies tested the role of preexisting familial and individual characteristics.
      METHODS: Data come from the TEMPO (Trajectoires Epidemiologiques en Population)
      study (community sample in France, 1991-2009, n=1103, 22-35 years in 2009) set up
      among offspring of participants of an epidemiological study (GAZEL). Past 12
      month substance use was assessed in 2009 by self-completed mail survey: regular
      tobacco smoking, alcohol abuse (AUDIT), cannabis use, problematic cannabis use
      (CAST), other illegal drug use. Socioeconomic position was defined by educational
      attainment, occupational grade, employment stability and unemployment. Covariates
      included demographics (age, sex, relationship status, parenthood), family
      background (parental income, parental tobacco smoking, parental alcohol use), and
      juvenile characteristics (psychological problems, academic difficulties) measured
      longitudinally. RESULTS: 35.8% of study participants were regular smokers, 14.3%
      abused alcohol, 22.6% used cannabis (6.3% had problematic cannabis use) and 4.1%
      used other illegal drugs. Except for alcohol abuse, substance use rates were
      systematically higher in individuals with low, rather than intermediate/high,
      socioeconomic position (age and sex-adjusted ORs from 1.75 for cannabis use to
      2.11 for tobacco smoking and 2.44 for problematic cannabis use). In multivariate
      analyses these socioeconomic disparities were decreased, but remained
      statistically significant (except for illegal drugs other than cannabis).
      CONCLUSIONS: Tobacco smoking, alcohol, cannabis and polysubstance use are common
      behaviors among young adults, particularly those experiencing socioeconomic
      disadvantage. Interventions aiming to decrease substance abuse and reduce
      socioeconomic inequalities in this area should be implemented early in life.

PMID- 21955363
TI  - The impact of active and passive peer influence on young adult smoking: an
      experimental study.
AB  - BACKGROUND: Peers influence adolescent and young adult smoking, but little is
      known about the underlying mechanisms. It is necessary to understand whether the
      current assumption of peer pressure is valid, or whether an alternative
      explanation as imitation is more appropriate. We examined whether passive
      (imitation) and/or active (pressure) peer influence affects young adult smoking.
      METHODS: An experiment was conducted among 68 daily-smoking students aged 16-24.
      The actual study aim was masked. Participants had to do a 30-min music task with
      a confederate. The experiment consisted of a 2 (smoking condition: confederate
      smokes or not) by 2 (pressure condition: confederate offers the participant a
      cigarette or not) factorial design, resulting in four conditions: (1) no smoking
      and no pressure (N=15); (2) smoking but no pressure (N=16); (3) pressure but no
      smoking (N=20); and (4) smoking and pressure (N=17). The primary outcome tested
      was the total number of cigarettes smoked during this music assignment. RESULTS:
      Peer smoking significantly predicted the total number of cigarettes smoked by
      young adults while peer pressure did not. The interaction effect of peer pressure
      and peer smoking was not significant. CONCLUSIONS: Peer pressure did not have a
      significant additional contribution, over and above smoking of the peer. Passive
      (imitation) peer influence affected young adult smoking rather than active
      (pressure) peer influence. Thus, smoking cessation efforts should aim at
      preventing interaction with smoking peers and raising awareness about its impact.

PMID- 21955364
TI  - Quantifying cannabis use with the timeline followback approach: a psychometric
      evaluation.
AB  - BACKGROUND: In the absence of a standardized cannabis unit, self-report
      instruments are inadequate for accurate quantification of cannabis use. The study
      extends the feasibility of using a cannabis substitute to reliably and validly
      measure quantity of cannabis use. METHOD: Ninety-eight adult Australian cannabis
      users (M age=27.98, SD=11.10; 65.31% male) completed a 90-day Timeline Followback
      interview regarding their cannabis use, utilizing the cannabis substitute
      Marijuanilla to report on quantity of use. Ninety-two of these individuals
      completed the interview at two time-points, and 56 of these participants had
      collaterals corroborate their cannabis use reports. RESULTS: Inter-rater
      reliability was excellent, while test-retest reliability was good to excellent.
      Intra-class correlation coefficients between participant and collateral reports,
      while similar to previous research, were unacceptable. Quantity of cannabis use
      statistically significantly added to frequency of use in predicting cannabis
      problems and dependence severity. Concurrent and discriminant validity were
      established with single-item and positive impression management measures,
      respectively. In addition, Marijuanilla appeared similar to one specimen of
      street seized cannabis, but not to two others. Importantly, participants'
      cravings to use cannabis did not increase as a result of using the cannabis
      substitute to report on their cannabis use. CONCLUSIONS: These data suggest that
      utilizing Marijuanilla to facilitate the reporting of grams of cannabis use may
      be reliable and valid; however, such comprehensive assessment may only be
      necessary for clinical trials and epidemiological studies, which rely on precise
      estimates of cannabis use.

PMID- 21955365
TI  - Internal reliability of measures of substance-related cognitive bias.
AB  - AIMS: There is growing interest in cognitive biases related to substance use, but
      evidence from the anxiety literature suggests that tasks commonly used to assess
      these may suffer from low internal reliability. We examined the internal
      reliability of the visual probe and modified Stroop tasks. DESIGN: Secondary
      analysis of visual probe and modified Stroop task data collected across seven
      independent studies. SETTING: Human laboratory study. PARTICIPANTS: Healthy
      volunteers (n=408 across seven independent studies) recruited from the general
      population on the basis of alcohol or tobacco use. MEASUREMENTS: Visual probe and
      modified Stroop task measures of substance-related cognitive bias. FINDINGS:
      Measures of cognitive bias for substance-related cues, as assayed by the visual
      probe and the modified Stroop tasks, may not be reliable. In particular, the
      visual probe task showed poor internal reliability, as did unblocked versions of
      the modified Stroop task. CONCLUSIONS: The modified Stroop task is preferable to
      the visual probe task as a measure of substance-related cognitive bias, on the
      basis of its psychometric properties. Studies using cognitive bias tasks should
      not assume they are reliable, and should routinely report reliability estimates
      where possible.

PMID- 21955366
TI  - Anatomic study of the mandibular foramen, lingula and antilingula in dry
      mandibles, and its statistical relationship between the true lingula and the
      antilingula.
AB  - The authors verified the anatomical location of the mandibular foramen, lingula
      and antilingula in dry mandibles, aiming to obtain information that could be used
      when performing mandibular osteotomies. Forty-four mandibles (88 sides) were
      evaluated. The distances were measured using a sliding calliper, with the
      mandibles fixed in a reproducible position. Results showed that the mandibular
      foramen is on average 5.82 mm below the lingula. Regarding the statistical
      comparison between the mandibular foramen entrance and the antilingula position,
      there is no correlation between the position of those two structures in the
      studied sample. The mandibular foramen is slightly posterior in relation to the
      centre of the ramus. The lingula is an important anatomic landmark for ramus
      surgery, and for determining the distance to the mandibular foramen entrance. The
      use of the antilingula as a landmark for the position of the vertical ramus
      osteotomy is not recommended.

PMID- 21955368
TI  - Drama as a pedagogical tool for practicing death notification-experiences from
      Swedish medical students.
AB  - BACKGROUND: One of the toughest tasks in any profession is the deliverance of
      death notification. Marathon Death is an exercise conducted during the fourth
      year of medical school in northern Sweden to prepare students for this
      responsibility. The exercise is designed to enable students to gain insight into
      the emotional and formal procedure of delivering death notifications. The
      exercise is inspired by Augusto Boal's work around Forum Theatre and is analyzed
      using video playback. The aim of the study was to explore reflections, attitudes
      and ideas toward training in delivering death notifications among medical
      students who participate in the Marathon Death exercise based on forum play.
      METHODS: After participation in the Marathon Death exercise, students completed
      semi-structured interviews. The transcribed interviews were analyzed using the
      principles of qualitative content analysis including a deductive content analysis
      approach with a structured matrix based on Bloom's taxonomy domains. RESULTS: The
      Marathon Death exercise was perceived as emotionally loaded, realistic and
      valuable for the future professional role as a physician. The deliverance of a
      death notification to the next of kin that a loved one has died was perceived as
      difficult. The exercise conjured emotions such as positive expectations and sheer
      anxiety. Students perceived participation in the exercise as an important
      learning experience, discovering that they had the capacity to manage such a
      difficult situation. The feedback from the video playback of the exercise and the
      feedback from fellow students and teachers enhanced the learning experience.
      CONCLUSIONS: The exercise, Marathon Death, based on forum play with video
      playback is a useful pedagogical tool that enables students to practice
      delivering death notification. The ability to practice under realistic conditions
      contributes to reinforce students in preparation for their future professional
      role.

PMID- 21955370
TI  - An fMRI study of the social competition in healthy subjects.
AB  - Social interaction requires the ability to infer another person's mental state
      (Theory of Mind, ToM) and also executive functions. This fMRI study aimed to
      identify the cerebral correlates activated by ToM during a specific social
      interaction, the human-human competition. In this framework, we tested a conflict
      resolution task (Stroop) adapted to a virtual situation of competition. The
      participants were instructed to play in order to win either against a human-like
      competitor (human-human competition) or against a non-human competitor (human
      machine competition). Only the human-human competition requires ToM as this type
      of competition is performed under social interaction. We identified first the
      classical network of executive regions activated by Stroop. Secondly, we
      identified the social (human-human) competition regions, represented by the
      bilateral superior and inferior frontal gyri, the anterior cingulate, the insula,
      the superior and anterior temporal, the hippocampus, the fusiform gyrus, the
      cuneus and the precuneus. Finally, we identified the executive regions that were
      modulated by the human-human competition, i.e., the executive control regions
      additionally activated when mentalizing in the context of social competition.
      They constituted a network predominant to the right and composed of the superior
      and middle frontal, anterior cingulate, insula and fusiform gyrus. We suggest
      that our experimental paradigm may be useful in exploration of the cerebral
      correlates of social adjustments in several situations such as psychiatric
      disorders presenting executive and social dysfunctions.

PMID- 21955369
TI  - Molecular pharmacological profile of a novel thiazolinone-based direct and
      selective 5-lipoxygenase inhibitor.
AB  - BACKGROUND AND PURPOSE: The potency of many 5-lipoxygenase (5-LOX) inhibitors
      depends on the cellular peroxide tone and the mechanism of 5-LOX enzyme
      activation. Therefore, new inhibitors that act regardless of the mode of enzyme
      activation need to be developed. Recently, we identified a novel class of
      thiazolinone-based compounds as potent 5-LOX inhibitors. Here, we present the
      molecular pharmacological profile of (Z)-5-(4-methoxybenzylidene)-2-(p-tolyl)-5H
      thiazol-4-one, compound C06. EXPERIMENTAL APPROACH: Inhibition of 5-LOX product
      formation was determined in intact cells [polymorphonuclear leukocytes (PMNL),
      rat basophilic leukaemia-1, RAW264.7] and in cell-free assays [homogenates, 100,
      000*g supernatant (S100), partially purified 5-LOX] applying different stimuli
      for 5-LOX activation. Inhibition of peroxisome proliferator-activated receptor
      (PPAR), cytosolic phospholipase A(2) (cPLA(2) ), 12-LOX, 15-LOX-1 and 15-LOX-2 as
      well as cyclooxygenase-2 (COX-2) were measured in vitro. KEY RESULTS: C06 induced
      non-cytotoxic, direct 5-LOX inhibition with IC(50) values about 0.66 uM (intact
      PMNL, PMNL homogenates) and approximately 0.3 uM (cell-free PMNL S100, partially
      purified 5-LOX). Action of C06 was independent of the stimulus used for 5-LOX
      activation and cellular redox tone and was selective for 5-LOX compared with
      other arachidonic acid binding proteins (PPAR, cPLA(2) , 12-LOX, 15-LOX-1, 15-LOX
      2, COX-2). Experimental results suggest an allosteric binding distinct from the
      active site and the C2-like domain of 5-LOX. CONCLUSIONS AND IMPLICATIONS: C06
      was identified as a potent selective direct 5-LOX inhibitor exhibiting a novel
      and unique mode of action, different from other established 5-LOX inhibitors.
      This thiazolinone may possess potential for intervention with inflammatory and
      allergic diseases and certain types of cancer.

PMID- 21955371
TI  - [DDG KOMPAKT - continuing education for German speaking dermatology].

PMID- 21955378
TI  - Autoimmune bullous skin diseases. Part 1: Clinical manifestations.
AB  - Autoimmune bullous skin diseases are characterized by autoantibodies against
      adhesion molecules of the skin. Pemphigus is a disorder with an intraepidermal
      loss of adhesion and is characterized by fragile blisters and erosions. Pemphigus
      vulgaris often shows extensive lesions of the oral mucosa, while pemphigus
      foliaceus is commonly restricted to cutaneous involvement with puff pastry-like
      scale formation. Paraneoplastic pemphigus is obligatorily associated with
      malignancies and often presents as hemorrhagic stomatitis with multiforme-like
      exanthems. IgA pemphigus typically presents with pustules and annular plaques but
      not with mucosal involvement. The clinical spectrum of the pemphigoids includes
      tense blisters, urticarial plaques, and prurigo- like eczematous lesions.
      Pemphigoid gestationis mostly occurs during the last trimester of pregnancy and
      mucous membrane pemphigoid primarily involves the oral mucosa and conjunctivae
      and leads to scarring. Linear IgA bullous dermatosis manifests with tense
      blisters in a "cluster of jewels"-like pattern in childhood and is more
      heterogeneous in adulthood. Classical epidermolysis bullosa acquisita shows
      extensive skin fragility. Dermatitis herpetiformis is associated with gluten
      sensitive enteropathy and manifests clinically with severe itching and
      papulovesicles on the extensor surfaces of the extremities and the lumbosacral
      area. The intention of the review is to demonstrate the heterogeneous clinical
      spectrum of autoimmune bullous disorders.

PMID- 21955380
TI  - [Recurring tumor on the lower chin of a 21-year old woman].

PMID- 21955382
TI  - Outdoor dynamic subject-specific evaluation of internal stresses in the residual
      limb: hydraulic energy-stored prosthetic foot compared to conventional energy
      stored prosthetic feet.
AB  - The prosthetic foot plays an important role in propelling, breaking, balancing
      and supporting body loads while the amputee ambulates on different grounds. It is
      therefore important to quantify the effect of the prosthetic foot mechanism on
      biomechanical parameters, in order to prevent pressure ulcers and deep tissue
      injury. Our aim was to monitor the internal stresses in the residuum of
      transtibial amputation (TTA) prosthetic-users ambulating on different terrains,
      which the amputees encounter during their daily activities, i.e. paved floor,
      grass, ascending and descending stairs and slope. We specifically aimed to
      compare between the internal stresses in the TTA residuum of amputees ambulating
      with a novel hydraulic prosthetic foot compared to conventional energy storage
      and return (ESR) prosthetic feet. Monitoring of internal stresses was
      accomplished using a portable subject-specific real-time internal stress monitor.
      We found significant decrease (p<0.01) in peak internal stresses and in the
      loading rate of the amputated limb, while walking with the hydraulic foot,
      compared to walking with ESR feet. The loading rate calculated while ambulating
      with the hydraulic foot was at least three times lower than the loading rate
      calculated while ambulating with the ESR foot. Although the average decrease in
      internal stresses was ~ 2-fold larger when replacing single-toe ESR feet with the
      hydraulic foot than when replacing split-toed ESR feet with the hydraulic foot,
      the differences were statistically insignificant. Our findings suggest that using
      a hydraulic prosthetic foot may protect the distal tibial end of the TTA residuum
      from high stresses, therefore preventing pressure-related injury and pain.

PMID- 21955383
TI  - Food-dependent, exercise-induced gastrointestinal distress.
AB  - Among athletes strenuous exercise, dehydration and gastric emptying (GE) delay
      are the main causes of gastrointestinal (GI) complaints, whereas gut ischemia is
      the main cause of their nausea, vomiting, abdominal pain and (blood) diarrhea.
      Additionally any factor that limits sweat evaporation, such as a hot and humid
      environment and/or body dehydration, has profound effects on muscle glycogen
      depletion and risk for heat illness. A serious underperfusion of the gut often
      leads to mucosal damage and enhanced permeability so as to hide blood loss,
      microbiota invasion (or endotoxemia) and food-born allergen absorption (with
      anaphylaxis). The goal of exercise rehydration is to intake more fluid orally
      than what is being lost in sweat. Sports drinks provide the addition of sodium
      and carbohydrates to assist with intestinal absorption of water and muscle
      glycogen replenishment, respectively. However GE is proportionally slowed by
      carbohydrate-rich (hyperosmolar) solutions. On the other hand, in order to
      prevent hyponatremia, avoiding overhydration is recommended. Caregiver's
      responsibility would be to inform athletes about potential dangers of drinking
      too much water and also advise them to refrain from using hypertonic fluid
      replacements.

PMID- 21955385
TI  - Evaluation of methylenetetrahydrofolate reductase gene variant (C677T) as risk
      factor for bipolar disorder.
AB  - Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of
      folate, whose role in bipolar disorder is controversial. The aim of the present
      study was to assess the risk of MTHFR C677T polymorphism for bipolar disorder.
      The author performed a meta-analysis and pooled data from individual case-control
      studies that examined the association between C677T polymorphism and bipolar
      disorder (meta-analysis: 8 studies, 1457 cases and 2169 controls).The pooled Odd
      Ratios (OR) were estimated by both fixed effects and random effects models. The
      meta-analysis with fixed effects showed that there was 71% heterogeneity between
      the eight studies. The fixed effect pooled OR was 1.07 (95% CI; 0.98 to 1.17) and
      Cochran Q was 24.13 (df = 7; p=0.0011). The study is significant and shows meager
      association. The random effect pooled OR was 1.07(95% CI; 0.87 to 1.32) and
      Cochran Q was 24.13 (df = 7; p=0.0011). The random effect pooled OR was also
      significant and shows meager association between MTHFR C677T genotype and bipolar
      disorder.

PMID- 21955384
TI  - Regulation of IL-2 gene expression by Siva and FOXP3 in human T cells.
AB  - BACKGROUND: Severe autoinflammatory diseases are associated with mutations in the
      Foxp3 locus in both mice and humans. Foxp3 is required for the development,
      function, and maintenance of regulatory T cells (Tregs), a subset of CD4 cells
      that suppress T cell activation and inflammatory processes. Siva is a pro
      apoptotic gene that is expressed across a range of tissues, including CD4 T
      cells. Siva interacts with three tumor necrosis factor receptor (TNFR) family
      members that are constitutively expressed on Treg cells: CD27, GITR, and OX40.
      RESULTS: Here we report a biophysical interaction between FOXP3 and Siva. We
      mapped the interaction domains to Siva's C-terminus and to a central region of
      FOXP3. We showed that Siva repressed IL-2 induction by suppressing IL-2 promoter
      activity during T cell activation. Siva-1's repressive effect on IL-2 gene
      expression appears to be mediated by inhibition of NFkappaB, whereas FOXP3
      repressed both NFkappaB and NFAT activity. CONCLUSIONS: In summary, our data
      suggest that both FOXP3 and Siva function as negative regulators of IL-2 gene
      expression in Treg cells, via suppression of NFAT by FOXP3 and of NFkappaB by
      both FOXP3 and Siva. Our work contributes evidence for Siva's role as a T cell
      signalling mediator in addition to its known pro-apoptotic function. Though
      further investigations are needed, evidence for the biophysical interaction
      between FOXP3 and Siva invites the possibility that Siva may be important for
      proper Treg cell function.

PMID- 21955386
TI  - Microbiological impact of treatment lagoons on the economics of water for reuse
      in agriculture a case study in Morocco (Settat and Soualem regions).
AB  - This study was undertaken to enumerate pathogens: fecal coliforms, Escherichia
      coli, fecal enterococci and Salmonella in the areas irrigated with treated
      wastewater. The samples were isolated from Settat (33 degrees 00'N, 7 degrees
      37'W) and Soualem regions (34 degrees 26'N, 5 degrees 53'W). A total of (n= 48)
      raw water, (n=48) treated water, (n=71) of vegetables samples irrigated by
      treated water taken from Waste Water Treatment Plant Settat; A total of (n=24)
      raw water, (n=24) treated water, (n=97) of vegetables samples irrigated by
      treated water taken from Waste Water Treatment Plant Soualem. The results show
      the total average in the two stations of raw water 7.9, 6.1 log MPN 100 ml-1 for
      respectively fecal coliforms and E. coli, 5.4 log CFU 100 ml-1 for fecal
      enterococci and 5.2 log MPN L-1 for Salmonella; for treated water 4.6, 3.1 log
      MPN 100 ml-1 for respectively fecal coliforms and E.coli and 3.5 log CFU 100 ml-1
      for fecal enterococci. Regarding plants, four types of crops were harvested and
      analyzed (forage, herbs, cereals and vegetables), the germs charges were found
      with fecal coliforms, E.coli and fecal enterococci respectively 3.2, 2.8 and 4.1
      log CFUg-1. Salmonella was never detected in both treated water and crops
      samples.

PMID- 21955387
TI  - Dietary restriction lowers endogenous levels of oxidative stress in different
      brain regions of adult mice.
AB  - Increase in the cellular burden of oxidative stress is critically involved in
      various pathological manifestations of aging, including age-related neurological
      disorders. Dietary restriction can lower reactive oxygen species formation, and
      thereby lower oxidative damage in the brain. The brain consists of a diverse
      group of neurons with varying functions. However, attenuating role of dietary
      restriction on oxidative stress in different regions of brain is not well known.
      In the present study we demonstrated that by restricting diet intake for a period
      of six months, mice lowered the endogenous levels of oxidative stress markedly by
      decreasing lipid peroxidation and protein carbonyl contents in cerebral cortex,
      hippocampus and striatum regions of the brain. Based on these results we suggest
      that dietary restriction can significantly reduce oxidative stress in various
      regions of the brain by virtue of lowering endogenous levels of reactive oxygen
      species, which might prove beneficial for preserving normal brain function with
      age.

PMID- 21955388
TI  - Neighborhood characteristics and TV viewing in youth: nothing to do but watch TV?
AB  - OBJECTIVES: Neighborhoods that discourage physical activity may encourage indoor
      activities such as television viewing; however few studies have examined
      associations between neighborhood characteristics and sedentary activities. This
      study examined cross-sectional and longitudinal associations between perceived
      and objective measures of the physical and social neighborhood environment and TV
      viewing among children and adolescents. DESIGN: Cross-sectional and longitudinal.
      METHODS: Parents of 190 children and 169 adolescents completed questionnaire
      items regarding facilities for physical activity, neighborhood safety (general
      and traffic), social trust/cohesion, social networks and their child's TV viewing
      in 2006. Adolescents self-reported their TV viewing. Objective measures of
      reported crime and neighborhood destinations, road connectivity and traffic
      exposure were also collected. Questions about TV viewing were repeated in 2008
      (longitudinal sample: 157 children; 105 adolescents). RESULTS: In children, cul
      de-sac density and reported crime were positively and parental agreement that
      their neighborhood has good sporting facilities was negatively associated with TV
      viewing in cross-sectional analyses. There were no longitudinal associations
      among children. In adolescents, number of sports options and parental agreement
      that there is so much traffic that it is difficult/unpleasant for their child to
      walk were negatively associated with TV viewing 2 years later. CONCLUSIONS: Crime
      and a lack of quality sporting facilities or options may contribute to greater TV
      viewing among youth.

PMID- 21955389
TI  - High success and low mortality rates with non-invasive ventilation in influenza A
      H1N1 patients in a tertiary hospital.
AB  - BACKGROUND: In 2009, an outbreak of respiratory illness caused by influenza A
      H1N1 virus occurred worldwide. Some patients required Intensive Care Unit (ICU)
      admission. The use of non-invasive ventilation (NIV) in these patients is
      controversial, as the aerosol dispersion may contaminate the environment and
      health-care co-workers. METHODS: Describe the respiratory profile, the mortality
      rate, and the benefit of using NIV in patients with confirmed diagnosis of
      influenza AH1N1 who were admitted in the ICU during the year 2009. RESULTS: A
      total of 1, 401 cases of influenza A H1N1 were confirmed in our hospital by real
      time RT-PCR in 2009, and 20 patients were admitted to the ICU. The patients' ages
      ranged from 18 to 74 years (median of 42). Acute Respiratory Failure (ARF) was
      present in 70% of patients. The median Acute Physiology and Chronic Health
      Evaluation II score was 7 (range 7 to 25). Of the 14 patients who developed ARF,
      85.7% needed NIV and 14% needed invasive MV at admission. Our success rate
      (41.6%) with NIV was higher than that described by others. The hospital mortality
      rate was 2.1%. When influenza A H1N1 arrived in Brazil, the disease was already
      on endemic alert in other countries. The population was already aware of the
      symptoms and the health-care system of the treatment. This allowed patients to be
      properly and promptly treated for influenza A H1N1, while health-care workers
      took protective measures to avoid contamination. CONCLUSION: In our study we
      found a high success and low mortality rates with non-invasive ventilation in
      patients with influenza A H1N1.

PMID- 21955391
TI  - The current issue: clinical shoulder, knee, wrist, hip, and cost-effectiveness
      analysis.

PMID- 21955392
TI  - [A rare cause of anemia in a chronic dialyzed patient].
AB  - We reported the case of a female in chronic dialysis since 3 years who developed
      a normocytic a regenerative anemia with no evident etiology. A bone marrow smear
      revealed a copper deficiency, a rare cause of anemia in general and dialyzed
      populations. Copper supplementation improved anemia with a decrease in
      transfusions rate and erythropoietin dosage. This case suggests that a copper
      deficiency has to be considered when a myelodysplastic syndrome is associated
      with neurologic symptoms and granulocytes precursors vacuolization identified in
      bone marrow smear. A blood titration of trace elements should be considered in
      front of a refractory anemia with no evident etiology.

PMID- 21955390
TI  - No evidence of a link between influenza vaccines and Guillain-Barre syndrome
      associated antiganglioside antibodies.
AB  - BACKGROUND: Guillain-Barre syndrome (GBS) is a rare autoimmune disease
      characterized by acute, progressive peripheral neuropathy and is commonly
      associated with the presence of antiganglioside antibodies. Previously, influenza
      vaccination was linked with the increased incidence of GBS; however, whether
      antiganglioside antibodies are subsequently induced remains unresolved. METHODS:
      Sera from human subjects vaccinated with seasonal influenza vaccines from the
      2007-2008, 2008-2009, or 1976-1977 influenza seasons were screened for the
      induction of immunity to influenza and the presence of antiganglioside antibodies
      pre- and post-vaccination. Likewise, sera from mice vaccinated with seasonal
      influenza vaccines (1988-1989, 2007-2008) or "swine flu" pandemic vaccines (1976,
      2009) were assessed in the same manner. Viruses were also screened for cross
      reacting ganglioside epitopes. RESULTS: Antiganglioside antibodies were found to
      recognize influenza viruses; this reactivity correlated with virus glycosylation.
      Antibodies to influenza viruses were detected in human and mouse sera, but the
      prevalence of antiganglioside antibodies was extremely low. CONCLUSIONS: Although
      the correlation between antiganglioside antibody cross-reactivity and
      glycosylation of viruses suggests the role of shared carbohydrate epitopes, no
      correlation was observed between hemagglutinin-inhibition titers and the
      induction of antiganglioside antibodies after influenza vaccination.

PMID- 21955393
TI  - [Dent's syndrome. Nephrology follow-up of four patients of the same family].
AB  - Dent's syndrome is a rare inherited tubulopathy. Factors influencing renal
      function in this disease are not well known. The aim of our study is to
      investigate the evolution of the Dent's syndrome in renal plan. The study was
      retrospective and conducted in 2006, concerning four brothers. The genetic defect
      was a mutation S244L missense in exon 6 of gene CLCN5. Various parameters were
      studied. Patients were 8.5 to 21-years-old at the beginning of the follow-up. Two
      of them had chronic renal insufficiency (CRI) which evolved, at least 7 years of
      moderate to terminal stage. Tubular signs were made of hypokalemia,
      hypercalciuria, hypophosphatemia and proteinuria mostly beta2 microglobulin.
      Improvement of these abnormalities was obtained with symptomatic treatment which
      has not always been well tolerated. A case of beginner nephrocalcinosis was
      observed. There was size and weight delay at the beginning of patient monitoring.
      Dent's syndrome may be complicated by CRI. It seems to appear in the second
      decade of life and hypercalciuria would contribute to it. Our CRI patients had
      significant bone disease. The hypercalciuria and proteinuria are factors over
      which we try to act. Clinical trials are needed to evaluate the efficacy of
      treatment on the reduction of CRI or its progression by reducing these factors in
      patients with Dent's syndrome.

PMID- 21955394
TI  - Classification of unknown primary tumors with a data-driven method based on a
      large microarray reference database.
AB  - We present a new method to analyze cancer of unknown primary origin (CUP)
      samples. Our method achieves good results with classification accuracy (88% leave
      one-out cross validation for primary tumors from 56 categories, 78% for CUP
      samples), and can also be used to study CUP samples on a gene-by-gene basis. It
      is not tied to any a priori defined gene set as many previous methods, and is
      adaptable to emerging new information.

PMID- 21955395
TI  - Association of elevated NTproBNP with recurrent thromboembolic events after acute
      pulmonary embolism.
AB  - INTRODUCTION: N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) is a predictor
      of adverse short-term clinical outcomes in patients with acute pulmonary embolism
      (APE), but its long-term prognostic value remains largely undefined. The aim of
      this study was to assess the value of plasma NTproBNP with regard to recurrent
      venous thromboembolism (VTE). MATERIALS AND METHODS: NTproBNP levels were
      measured in 224 consecutive patients with the first episode of acute pulmonary
      embolism occurring from January 2005 through October 2010. Patients were
      categorized into two groups by NTproBNP reference range. Follow-ups were
      performed at 3, 6, and 12months and yearly thereafter. The primary end point was
      symptomatic, recurrent fatal or nonfatal VTE. RESULTS: NTproBNP was elevated in
      158 (70.5%) patients and not elevated in 66 (29.5%) patients. After a mean follow
      up period of 31.0+/-19.4months, patients with elevated NTproBNP showed an
      increased risk of recurrent VTE (20 patients, 12.7%) compared to those without
      elevated NTproBNP (only 1 patient, 1.5%) (P=0.009). Of the 7 deaths related to
      pulmonary embolism, 6 occurred in patients with elevated NTproBNP compared to
      patients with normal NTproBNP (1 of 7 deaths). In a multivariate analysis
      stratified by oral anticoagulant treatment duration, elevated NTproBNP was an
      independent predictor of recurrent VTE (hazard ratio, 9.32; P=0.02). CONCLUSIONS:
      Elevated NTproBNP is associated with recurrent VTE in acute pulmonary embolism
      patients.

PMID- 21955396
TI  - Epilogue: Lessons from the CONVERGE study of major depressive disorder in China.
AB  - This review summarizes the first clinical reports from the CONVERGE consortium:
      China, Oxford and VCU Experimental Research on Genetic Epidemiology. CONVERGE
      sets out to investigate the nature and mode of action of the genetic and
      environmental risk factors for major depressive disorder (MDD). CONVERGE aims to
      collect 6000 cases of recurrent MDD and 6000 controls. The consortium includes
      hospitals in 30 cities, all with populations exceeding 5million, and has
      collected over 2000 cases and controls. High quality phenotype data on MDD
      collected in China is now available to determine the source and nature of this
      highly heterogeneous condition. Analyses reported in a series of papers indicate
      that the clinical features and risk factors of MDD are sufficiently similar to
      those in the West that we can confidently predict that the results of subsequent
      analyses will be widely applicable.

PMID- 21955397
TI  - Identification of a cluster of PR4-like genes involved in stress responses in
      rice.
AB  - PR4 proteins constitute a pathogenesis-related (PR) protein family with a
      conserved BARWIN domain. In this study, we analyzed PR4-homologous genes in rice
      (Oryza sativa L.) and identified five putative PR4 genes designated as OsPR4a-e.
      The five PR4 genes are located in tandem on chromosome 11 and constitute a gene
      cluster with high sequence similarity to each other. The OsPR4 proteins have high
      sequence similarity to reported PR4 proteins from monocotyledonous species and
      are predicted to be class II PR4 proteins. Distinct diversification of plant PR4
      proteins exists between monocotyledonous and dicotyledonous plants. Except for
      OsPR4e, which was not detected with any transcript, the other four OsPR4 genes
      showed diverse temporal-spatial expression patterns, and their expressions are
      responsive to Magnaporthe grisea infection. Interestingly, the OsPR4 genes are
      also responsive to abiotic stresses. Their expression levels were strongly
      induced by at least one of the stress treatments including drought, salt, cold,
      wounding, heat shock, and ultraviolet. The transcript levels of OsPR4 genes were
      also induced by some phytohormones such as abscisic acid and jasmonic acid.
      Transgenic rice with overexpression of OsPR4a showed enhanced tolerance to
      drought at both seedling and reproductive stages. We conclude that rice PR4 genes
      are also involved in abiotic stress responses and tolerance in addition to their
      responsiveness to pathogen attacks.

PMID- 21955399
TI  - Trusts are told to prioritise high risk general surgical patients.

PMID- 21955400
TI  - Effectiveness of an ultrasound training module for internal medicine residents.
AB  - BACKGROUND: Few internal medicine residency programs provide formal ultrasound
      training. This study sought to assess the feasibility of simulation based
      ultrasound training among first year internal medicine residents and measure
      their comfort at effectively using ultrasound to perform invasive procedures
      before and after this innovative model of ultrasound training. METHODS: A
      simulation based ultrasound training module was implemented during intern
      orientation that incorporated didactic and practical experiences in a simulation
      and cadaver laboratory. Participants completed anonymous pre and post surveys in
      which they reported their level of confidence in the use of ultrasound technology
      and their comfort in identifying anatomic structures including: lung, pleural
      effusion, bowel, peritoneal cavity, ascites, thyroid, and internal jugular vein.
      Survey items were structured on a 5-point Likert scales (1 = extremely
      unconfident, 5 = extremely confident). RESULTS: Seventy-five out of seventy-six
      interns completed the pre-intervention survey and 55 completed the post-survey.
      The mean confidence score (SD) increased to 4.00 (0.47) (p < 0.0001). The mean
      (SD) comfort ranged from 3.61 (0.84) for peritoneal cavity to 4.48 (0.62) for
      internal jugular vein. Confidence in identifying all anatomic structures showed
      an increase over the pre-intervention means (p < 0.002). CONCLUSION: A simulation
      based ultrasound learning module can improve the self-reported confidence with
      which residents identify structures important in performing invasive ultrasound
      guided procedures. Incorporating an ultrasound module into residents' education
      may address perceived need for ultrasound training, improve procedural skills,
      and enhance patient safety.

PMID- 21955398
TI  - Quantitative chemical proteomics reveals new potential drug targets in head and
      neck cancer.
AB  - Tumors of the head and neck represent a molecularly diverse set of human cancers,
      but relatively few proteins have actually been shown to drive the disease at the
      molecular level. To identify new targets for individualized diagnosis or
      therapeutic intervention, we performed a kinase centric chemical proteomics
      screen and quantified 146 kinases across 34 head and neck squamous cell carcinoma
      (HNSCC) cell lines using intensity-based label-free mass spectrometry.
      Statistical analysis of the profiles revealed significant intercell line
      differences for 42 kinases (p < 0.05), and loss of function experiments using
      siRNA in high and low expressing cell lines identified kinases including EGFR,
      NEK9, LYN, JAK1, WEE1, and EPHA2 involved in cell survival and proliferation.
      EGFR inhibition by the small molecule inhibitors lapatinib, gefitinib, and
      erlotinib as well as siRNA led to strong reduction of viability in high but not
      low expressing lines, confirming EGFR as a drug target in 10-20% of HNSCC cell
      lines. Similarly, high, but not low EPHA2-expressing cells showed strongly
      reduced viability concomitant with down-regulation of AKT and ERK signaling
      following EPHA2 siRNA treatment or EPHA1-Fc ligand exposure, suggesting that
      EPHA2 is a novel drug target in HNSCC. This notion is underscored by
      immunohistochemical analyses showing that high EPHA2 expression is detected in a
      subset of HNSCC tissues and is associated with poor prognosis. Given that the
      approved pan-SRC family kinase inhibitor dasatinib is also a very potent
      inhibitor of EPHA2, our findings may lead to new therapeutic options for HNSCC
      patients. Importantly, the strategy employed in this study is generic and
      therefore also of more general utility for the identification of novel drug
      targets and molecular pathway markers in tumors. This may ultimately lead to a
      more rational approach to individualized cancer diagnosis and therapy.

PMID- 21955402
TI  - Microbial-induced immunomodulation by targeting the NF-kappaB system.
AB  - Virtually all eukaryotes have developed defense mechanisms to efficiently counter
      potential threats from prokaryotic microorganisms; an example is the conserved
      nuclear factor-kappaB (NF-kappaB) signaling system. However, bacterial pathogens
      and commensals have in turn evolved highly effective counter mechanisms to
      modulate this immune regulatory circuit. Modifications in ubiquitin, ubiquitin
      like (Ubl) proteins such as neural precursor cell expressed, developmentally down
      regulated 8 (NEDD8) and other post-translational modifications (PTMs) in the NF
      kappaB system represent attractive targets for microbial manipulation. In this
      review, we describe recent advances in understanding the different strategies
      that bacteria have evolved to interfere with PTMs in NF-kappaB signal
      transmission.

PMID- 21955401
TI  - Increased APOBEC3G and APOBEC3F expression is associated with low viral load and
      prolonged survival in simian immunodeficiency virus infected rhesus monkeys.
AB  - BACKGROUND: The cytidine deaminases APOBEC3G (A3G) and APOBEC3F (A3F) are innate
      cellular factors that inhibit replication of a number of viruses, including HIV
      1. Since antiviral activity of APOBEC3 has been mainly confirmed by in vitro
      data, we examined their role for disease progression in the SIV/macaque model for
      AIDS. RESULTS: We quantified A3G and A3F mRNA in PBMC and leukocyte subsets of
      uninfected and SIVmac-infected rhesus macaques. Compared with uninfected animals,
      we found increased A3G and A3F mRNA levels in PBMC, purified CD4+ T-cells and
      CD14+ monocytes as well as lymph node cells from asymptomatic SIV-infected
      macaques. APOBEC3 mRNA levels correlated negatively with plasma viral load, and
      highest amounts of APOBEC3 mRNA were detected in long term non-progressors
      (LTNPs). During acute viremia, A3G mRNA increased in parallel with MxA, a
      prototype interferon-stimulated gene indicating a common regulation by the
      initial interferon response. This association disappeared during the asymptomatic
      stage. CONCLUSION: Our findings suggest a protective effect of APOBEC3 for HIV
      and SIV in vivo and indicate regulation of APOBEC3 by interferon during early
      infection and by contribution of other, hitherto undefined factors at later
      disease stages. Elucidating the regulatory mechanisms leading to increased
      APOBEC3 mRNA levels in LTNPs could help to develop new therapies against HIV.

PMID- 21955403
TI  - Effects of combining simvastatin with rosiglitazone on inflammation, oxidant
      stress and ambulatory blood pressure in patients with the metabolic syndrome: the
      SIROCO study.
AB  - AIM: Individually, statins and thiazolidinediones (TZDs) show positive effects on
      atherosclerosis progression in cellular and animal models as well as patients
      with diabetes; however, their combined effects have not been studied. This study
      examines the effects of simvastatin combined with rosiglitazone on vascular
      inflammation, oxidant stress, ambulatory blood pressure (BP) and other
      atherosclerotic factors in patients with the metabolic syndrome. METHODS: This is
      a randomized, double blind, placebo-controlled study in 53 subjects with the
      metabolic syndrome. Participants were randomized to simvastatin 40 mg/day plus
      placebo vs. simvastatin 40 mg/day plus rosiglitazone 4 mg/day for 6 months. The
      primary endpoint was the between-group difference in high-sensitivity C-reactive
      protein (hs-CRP) and secondary variables including urinary isoprostanes, serum
      malondialdehyde (MDA), ambulatory BP, adiponectin, and lipid and glycaemic
      profiles. RESULTS: At study end, the group randomized to the
      simvastatin/rosiglitazone combination had a greater reduction in hs-CRP of 1.33
      mg/dl, (p = 0.029) and showed a trend for a greater reduction in urinary
      isoprostane (-39%), (p = 0.056) compared to simvastatin/placebo group. Changes in
      MDA levels did not differed between groups (p = 0.81). 24-h systolic blood
      pressure (SBP) also showed a 4.5 mmHg reduction at 6 months (p = 0.06).
      Adiponectin levels increased by 3.91 ug/ml in the combination group over placebo,
      (p = 0.03) and blood glucose decreased in combination group vs. placebo.
      CONCLUSION: Our data show that patients with the metabolic syndrome given a
      statin/TZD combination manifest greater reductions in markers of vascular
      inflammation and oxidant stress, 24-h ambulatory BP and increases in adiponectin
      as well as improved glycaemic indices.

PMID- 21955404
TI  - The expression and role of protein kinase C (PKC) epsilon in clear cell renal
      cell carcinoma.
AB  - Protein kinase C epsilon (PKCepsilon), an oncogene overexpressed in several human
      cancers, is involved in cell proliferation, migration, invasion, and survival.
      However, its roles in clear cell renal cell carcinoma (RCC) are unclear. This
      study aimed to investigate the functions of PKCepsilon in RCC, especially in
      clear cell RCC, to determine the possibility of using it as a therapeutic target.
      By immunohistochemistry, we found that the expression of PKCepsilon was up
      regulated in RCCs and was associated with tumor Fuhrman grade and T stage in
      clear cell RCCs. Clone formation, wound healing, and Borden assays showed that
      down-regulating PKCepsilon by RNA interference resulted in inhibition of the
      growth, migration, and invasion of clear cell RCC cell line 769P and, more
      importantly, sensitized cells to chemotherapeutic drugs as indicated by enhanced
      activity of caspase-3 in PKCepsilon siRNA-transfected cells. These results
      indicate that the overexpression of PKCepsilon is associated with an aggressive
      phenotype of clear cell RCC and may be a potential therapeutic target for this
      disease.

PMID- 21955405
TI  - Dietary treatments: the road from Phoenix to Edinburgh.
AB  - The ketogenic diet is now an established treatment in children for drug resistant
      epilepsy. Although in use for almost 100 years, it has taken time for us to
      determine an evidence base to verify its use in these children. However,
      increasing research both from a clinical and basic science perspective as well as
      a wide clinical interest has now enabled its use throughout the world. This
      aside, there remains lack of resources to guarantee its availability to all those
      who may be suitable. It is also now quite clear that it may have benefit in wider
      areas of neurology beyond epilepsy, specifically in metabolic disorders where
      glucose cannot be used as a primary energy source.

PMID- 21955407
TI  - [Control of coronary heart disease risk factors and evidence-based therapies:
      joint efforts for coronary heart disease prevention in Spain].

PMID- 21955408
TI  - Ban drug advertisements.

PMID- 21955409
TI  - Dextromethorphan abuse in teens: beware acetaminophen poisoning!

PMID- 21955410
TI  - Prehospital analgesia in Ontario.

PMID- 21955406
TI  - Targeting glutamate synapses in schizophrenia.
AB  - Although early clinical observations implicated dopamine dysfunction in the
      neuropathology of schizophrenia, accumulating evidence suggests that multiple
      neurotransmitter pathways are dysregulated. The psychotomimetic actions of NMDA
      receptor antagonists point to an imbalance of glutamatergic signaling.
      Encouragingly, numerous preclinical and clinical studies have elucidated several
      potential targets for increasing NMDA receptor function and equilibrating
      glutamatergic tone, including the metabotropic glutamate receptors 2, 3 and 5,
      the muscarinic acetylcholine receptors M(1) and M(4), and the glycine transporter
      GlyT1. Highly specific allosteric and orthosteric ligands have been developed
      that modify the activity of these novel target proteins, and in this review we
      summarize both the glutamatergic mechanisms and the novel compounds that are
      increasing the promise for a multifaceted pharmacological approach to treat
      schizophrenia.

PMID- 21955411
TI  - Prioritizing performance measurement for emergency department care: consensus on
      evidence-based quality of care indicators.
AB  - BACKGROUND: The evaluation of emergency department (ED) quality of care is
      hampered by the absence of consensus on appropriate measures. We sought to
      develop a consensus on a prioritized and parsimonious set of evidence-based
      quality of care indicators for EDs. METHODS: The process was led by a nationally
      representative steering committee and expert panel (representatives from hospital
      administration, emergency medicine, health information, government, and
      provincial quality councils). A comprehensive review of the scientific literature
      was conducted to identify candidate indicators. The expert panel reviewed
      candidate indicators in a modified Delphi panel process using electronic surveys;
      final decisions on inclusion of indicators were made by the steering committee in
      a guided nominal group process with facilitated discussion. Indicators in the
      final set were ranked based on their priority for measurement. A gap analysis
      identified areas where future indicator development is needed. A feasibility
      study of measuring the final set of indicators using current Canadian
      administrative databases was conducted. RESULTS: A total of 170 candidate
      indicators were generated from the literature; these were assessed based on
      scientific soundness and their relevance or importance. Using predefined scoring
      criteria in two rounds of surveys, indicators were coded as "retained" (53),
      "discarded" (78), or "borderline" (39). A final set of 48 retained indicators was
      selected and grouped in nine categories (patient satisfaction, ED operations,
      patient safety, pain management, pediatrics, cardiac conditions, respiratory
      conditions, stroke, and sepsis or infection). Gap analysis suggested the need for
      new indicators in patient satisfaction, a healthy workplace, mental health and
      addiction, elder care, and community-hospital integration. Feasibility analysis
      found that 13 of 48 indicators (27%) can be measured using existing national
      administrative databases. DISCUSSION: A broadly representative modified Delphi
      panel process resulted in a consensus on a set of 48 evidence-based quality of
      care indicators for EDs. Future work is required to generate technical
      definitions to enable the uptake of these indicators to support benchmarking,
      quality improvement, and accountability efforts.

PMID- 21955412
TI  - Consensus on paramedic clinical decisions during high-acuity emergency calls:
      results of a Canadian Delphi study.
AB  - OBJECTIVES: To establish consensus on the most important clinical decisions
      paramedics make during high-acuity emergency calls and to visualize these
      decisions on a process map of an emergency call. A secondary objective was to
      measure agreement among paramedics and medical director panel members. METHODS: A
      multiround online survey of Canadian paramedics and medical directors. In round
      1, participants listed important clinical decisions. In round 2, participants
      scored each decision in terms of its importance for patient outcome and safety.
      In rounds 3 and 4, participants could revise their scores. Consensus was defined
      a priori: 80% or more agreement that a decision was important or extremely
      important. The included decisions were plotted on a process map of a typical
      emergency call. RESULTS: The panel response rates were as follows: round 1, 96%;
      round 2, 92%; round 3, 83%; and round 4, 96%. Consensus was reached on 42
      decisions, grouped into six categories: airway management (n  =  13); assessment
      (n  =  3); cardiac management (n  =  7); drug administration (n  =  9); scene
      management (n  =  4); and general treatment (n  =  6). The on-scene treatment
      phase of the process map was found to have the highest decision density.
      Paramedics and medical directors differed in their scoring in 5 of 42 decisions
      (p < 0.05 or less). CONCLUSION: Consensus was reached among paramedics and
      medical directors on 42 decisions important for clinical outcome and patient
      safety. These decisions were visualized on a process map of an emergency call to
      learn more about where decision density exists during a typical call.

PMID- 21955413
TI  - Residents-as-teachers: a survey of Canadian specialty programs.
AB  - INTRODUCTION: The ability to teach is a critical component of residency and
      future practice. This is recognized by the Royal College of Physicians and
      Surgeons of Canada, which incorporates teaching functions into the CanMEDS
      competencies. The aim of our study was to identify how emergency medicine
      specialty programs across Canada prepare their residents for roles as teachers
      and to compare these results to those of other Royal College specialty programs.
      METHODS: A 40-item English questionnaire was developed and translated into
      French. It was e-mailed to the program directors of all Royal College Emergency
      Medicine (EM), Anesthesia, Diagnostic Radiology, General Surgery, Internal
      Medicine, Obstetrics and Gynecology, Pediatrics, and Psychiatry residency
      programs. The survey asked what modalities were in use to teach residents how to
      teach and allowed respondents to comment on recent changes. RESULTS: Twelve of 13
      (92%) EM programs and 78 of 113 (69%) other specialty programs responded. All
      responding programs incorporated some kind of mandatory teaching
      responsibilities. Four of 12 (33%) EM programs reserved formal teaching functions
      for postgraduate year 3 and above, whereas only 7 of 78 (9%) other specialty
      programs did so. The remaining 71 of 78 (91%) non-EM specialty programs
      incorporated formal teaching functions in all years of residency. Six of 12 (50%)
      EM programs offered rotations in clinical medical education compared to only 11
      of 78 (14%) other specialty programs. CONCLUSIONS: Canadian EM programs appear to
      differ from other specialty programs in the way that they develop residents-as
      teachers. Half of EM programs offer rotations in clinical medical education, and
      many introduce formal teaching functions later in residency.

PMID- 21955414
TI  - Application of Lean principles to improve early cardiac care in the emergency
      department.
AB  - OBJECTIVE: To achieve our goal of excellent emergency cardiac care, our
      institution embarked on a Lean process improvement initiative. We sought to
      examine and quantify the outcome of this project on the care of suspected acute
      coronary syndrome (ACS) patients in our emergency department (ED). METHODS: Front
      line ED staff participated in several rapid improvement events, using Lean
      principles and techniques such as waste elimination, supply chain streamlining,
      and standard work to increase the value of the early care provided to patients
      with suspected ACS. A chart review was also conducted. To evaluate our success,
      proportions of care milestones (first electrocardiogram [ECG], ECG
      interpretation, physician assessment, and acetylsalicylic acid [ASA]
      administration) meeting target times were chosen as outcome metrics in this
      before-and-after study. RESULTS: The proportion of cases with 12-lead ECGs
      completed within 10 minutes of patient triage increased by 37.4% (p < 0.0001).
      The proportion of cases with physician assessment initiated within 60 minutes
      increased by 12.1% (p  =  0.0251). Times to ECG, physician assessment, and ASA
      administration also continued to improve significantly over time (p values <
      0.0001). Post-Lean, the median time from ECG performance to physician
      interpretation was 3 minutes. All of these improvements were achieved using
      existing staff and resources. CONCLUSIONS: The application of Lean principles can
      significantly improve attainment of early diagnostic and therapeutic milestones
      of emergency cardiac care in the ED.

PMID- 21955415
TI  - Use of the Ottawa Ankle Rules in children: a survey of physicians' practice
      patterns.
AB  - INTRODUCTION: A number of studies have assessed the diagnostic accuracy of the
      Ottawa Ankle Rules (OAR) in children; however, the role of the OAR in guiding
      physician radiograph use is unclear. OBJECTIVES: The primary purpose of this
      study was to determine the extent to which Canadian pediatric emergency
      physicians report using the OAR. Secondary goals included determining current
      diagnostic and management strategies for Salter-Harris 1 (SH-1) injuries of the
      ankle and which fractures physicians deem to be clinically significant. METHODS:
      A self-administered piloted survey was distributed by mail to 215 Canadian
      pediatric emergency physicians using a modified Dillman technique. Participants
      were selected through Pediatric Emergency Research Canada (PERC), a national
      network of health care professionals with an interest in pediatric emergency
      medicine research. RESULTS: Of 209 surveys, 144 were returned, for a response
      rate of 68.9%. Of those, 87.5% (126 of 144) reported applying the OAR in children
      to determine the need for radiographs in acute ankle or midfoot injuries. Of
      those, 65.1% reported using the OAR always or usually, and 64.5% (93 of 144) of
      physicians stated that they believe all ankle fractures are clinically
      significant. Although physicians report that they most commonly order the
      radiographs, 36.2% of participants indicated that radiographs were requisitioned
      by nurses or other health care providers at their facilities. SH-1 fractures were
      reported to be most commonly managed by immobilization (83.3%; 120 of 144), with
      most patients going on to follow-up with an orthopedic surgeon. CONCLUSIONS: The
      majority of Canadian pediatric emergency physicians indicate that they use the
      OAR when assessing children with acute ankle and midfoot injuries. Most
      physicians believe that all ankle fractures, including SH-1, are clinically
      significant and have a management preference for immobilization and orthopedic
      follow-up.

PMID- 21955416
TI  - How do I audit and receive feedback on my clinical practice?
AB  - Audit and feedback (A&F) is a powerful exercise for self-assessment of individual
      or group practice against best practice. Learning occurs through a structured
      process, starting by understanding the area of interest, conducting an audit, and
      then reflecting and creating solutions to identified gaps in care. Although
      current evidence is limited, the additional time and effort required are believed
      to result in greater rewards than traditional educational activities as the
      learning is more directly relevant to patient care.

PMID- 21955417
TI  - More than a laceration: a case of pneumocephalus.

PMID- 21955418
TI  - Keeping an open mind about meningitis: a case report of carcinomatous meningitis.
AB  - Carcinomatous meningitis is defined as leptomeningeal infiltration by malignant
      cells. A case of carcinomatous meningitis, originally diagnosed as viral
      meningitis, is presented here to highlight the importance of maintaining a broad
      differential diagnosis in patients with evidence of meningeal irritation.
      Clinical and laboratory clues that suggest a diagnosis of carcinomatous
      meningitis in a patient with meningeal irritation include the presence and type
      of underlying malignancy (more common with breast cancer, lung cancer, and
      melanoma), absence of fever, presence of radicular pain, evidence of both cranial
      and spinal involvement, consistent cerebrospinal fluid (CSF) findings (increased
      opening pressure, elevated protein concentration, decreased glucose, increased
      white cell count), and supportive neuroimaging. Diagnosis is based on positive
      CSF cytology results, which may require multiple lumbar puncture procedures to
      obtain. For patients with a known primary malignancy who present to the emergency
      department with symptoms and/or signs of meningeal irritation, carcinomatous
      meningitis should be included in the differential diagnosis.

PMID- 21955419
TI  - Surfer's myelopathy: case report and review.
AB  - Nontraumatic spinal cord injury from surfing is a new entity first described in
      2004 and likely of ischemic etiology. We report the case of a 25-year-old man who
      presented to the emergency department with a 2-week history of lower extremity
      weakness after surfing in Indonesia. The patient reported developing low back
      pain, lower extremity weakness, sensory changes, and urinary retention shortly
      after his first surfing lesson. The patient was subsequently diagnosed with
      surfer's myelopathy. The purpose of this report is to review the clinical
      presentation, etiology, risk factors, and management of this increasingly
      described entity.

PMID- 21955422
TI  - Immunolocalization and expression of lubricin in the bilaminar zone of the human
      temporomandibular joint disc.
AB  - Lubricin, which is a boundary joint lubricant, was investigated
      immunohistochemically in the bilaminar zone (BZ) of the human temporomandibular
      joint (TMJ), without any degenerative changes. Immunohistochemistry for lubricin
      detection was carried out on 33 TMJ discs obtained from 17 cadavers. Sections
      were incubated with diluted rabbit polyclonal anti-lubricin antibody and scored
      according to the percentage of lubricin immunopositive cells. Three different TMJ
      disc tissue compartments were analyzed, namely: the upper lamina, the inferior
      lamina and the loose connective tissue in the space between the laminae. The Mann
      Whitney U test was used to compare protein expression (lubricin) among disc
      specimens' regions. Staining was noted within the TMJ disc cell populations in
      every disc tissue sample, with almost every cell immunolabeled by the lubricin
      antibody. The number of disc cells immunolabeled was almost the same in the 3
      bilaminar zone regions. Positive extracellular matrix staining was also seen. The
      results of the present study suggest that lubricin is expressed in the TMJ disc
      bilaminar zone. Lubricin may have a role in normal disc posterior attachment
      physiology through the prevention of cellular adhesion as well as providing
      lubrication during normal bilaminar zone function.

PMID- 21955423
TI  - Magnetic endoscopic imaging as a guide to smart colonoscopy.

PMID- 21955424
TI  - World gastroenterology organisation global guideline: Helicobacter pylori in
      developing countries.

PMID- 21955425
TI  - The role of p38 mitogen-activated protein kinase in the pathogenesis of
      inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) includes ulcerative colitis and Crohn's disease
      which is characterized by the recurrent intestinal inflammation and overactive
      immune responses. The signaling pathways of p38 mitogen-activated protein kinase
      (MAPK) play an important role in bowel inflammation. The inhibition of p38 MAPK
      can effectively suppress the expression of inflammatory mediators. However, due
      to the obvious preclinical and clinical side effects, p38 inhibitors are
      unacceptable in safety profiles and cannot be applied in the treatment of IBD.
      MAPK-activated protein kinase 2 (MK2), as the direct substrate of p38alpha and
      p38beta, is a multifunctional signaling protein in the progression of
      inflammation and several lines of evidence demonstrate that the inhibition of MK2
      may produce the same beneficial effect as the inhibition of p38 MAPK. Hence, MK2
      is likely to be a potential drug target for the treatment of IBD.

PMID- 21955426
TI  - Is impedance pH monitoring superior to the conventional 24-h pH meter in the
      evaluation of patients with laryngorespiratory symptoms suspected to be due to
      gastroesophageal reflux disease?
AB  - OBJECTIVE: Cough and laryngo-pharyngeal symptoms (LPS) are associated with
      gastroesophageal reflux disease (GERD). The role of acid reflux (AR) and non-acid
      reflux (NAR) in atypical GERD pathogenesis is controversial. The aims of the
      study were to determine the prevalence of high esophageal acid exposure time
      (AET) in patients presenting with cough or LPS and determine the incremental
      yield of multichannel intraluminal impedance-pH (MII-pH) monitoring. METHODS: We
      undertook a prospective study of patients with cough or LPS referred for GERD
      evaluation between January 2009 and May 2011. All patients underwent esophageal
      manometry, gastroscopy and MII-pH. Patients' characteristics, gastroscopy
      findings, distal esophageal AET, bolus exposure (BE) time and numbers of AR and
      NAR episodes in the proximal and distal esophagus were studied. RESULTS: Overall
      50 patients (22 male, mean age 47.5 +/- 14.2 years) were evaluated for
      unexplained chronic cough (n = 23, 46.0%), and LPS symptoms including globus (n =
      10, 20.0%), sore throat (n = 12, 24.0%) and hoarse voice (n = 5, 10.0%). A normal
      gastroscopy, Los Angeles grade A and B esophagitis occurred in 44 (88.0%), 5
      (10.0%) and 1 (2.0%) patient, respectively. Seven (14.0%) recorded elevated AET
      (chronic cough, 4; sore throat, 2; and hoarse voice, 1). Nine patients recorded
      abnormal impedance characteristics (raised BE time and/or increased reflux
      numbers) despite a normal AET leading to an incremental diagnostic yield of 18%.
      CONCLUSION: An isolated high AET is uncommon in patients with cough or LPS.
      Combined MII-pH improves the diagnostic yield in patients with atypical GERD
      manifestations.

PMID- 21955427
TI  - The role of HIF-1, angiopoietin-2, Dll4 and Notch1 in bleeding gastrointestinal
      vascular malformations and thalidomide-associated actions: a pilot in vivo study.
AB  - OBJECTIVE: To investigate plasma levels of hypoxia inducible factor-1 (HIF-1),
      angiopoietin-2 (Ang-2), Delta-like ligand 4 (Dll4) and Notch1 in patients with
      recurrent gastrointestinal bleeding due to gastrointestinal vascular malformation
      (GIVM) with or without thalidomide treatment. METHODS: Ten eligible patients with
      recurrent gastrointestinal bleeding due to GIVM, who received thalidomide 100
      mg/d for 4 months, were followed up for 1 year. The effective response was the
      proportions of patients with yearly bleeding episodes reduced by >=50% at 1 year
      after treatment. Plasma levels of HIF-1, Ang-2, Dll4 and Notch1 were measured
      using enzyme-linked immunosorbent assay in the GIVM thalidomide treatment group
      before and after treatment (10 patients), the GIVM non-thalidomide treatment
      group (25 patients) and the control group (18 participants). RESULTS: In the GIVM
      thalidomide treatment group, eight patients (8/10) achieved effective response
      and five (5/10) displayed complete cessation of bleeding. Mean plasma levels of
      HIF-1, Ang-2, Dll4 and Notch1 were all higher in the GIVM thalidomide and non
      thalidomide treatment groups than in the control group (all P < 0.001). However,
      Ang-2 decreased more significantly in the effective subgroups (P = 0.003) and no
      bleeding patients (P = 0.008). CONCLUSIONS: HIF-1, Ang-2, Dll4 and Notch1 might
      participate in the formation of GIVM. Thalidomide is an effective and safe
      treatment agent for GIVM and its associated bleeding. The reduction degree of Ang
      2 after a 4-month treatment of thalidomide may offer values for evaluating its
      prognosis and efficacy.

PMID- 21955428
TI  - Improved diagnostic yield with severity of bleeding.
AB  - OBJECTIVE: Video capsule endoscopy (VCE) is an important tool for non-invasive
      imaging of the small bowel. Whether there is a dose-related effect of anemia
      severity on the diagnostic yield of VCE is unknown. The aim of this study was to
      determine the influence of anemia severity on VCE outcome measures. METHODS: VCE
      studies from the Sacramento Veterans Affairs Medical Center for 300 consecutive
      patients were retrospectively screened. Those with anemia were selected. Patients
      were grouped as mildly, moderately or severely bleeding. Outcomes data including
      completion of study, diagnostic yield and further intervention were compared.
      RESULTS: Of the 300 patients, 210 (70%) were found to have anemia. Overall 32
      (15.24%) patients were mildly, 145 (69.05%) were moderately and 33 (15.71%) were
      severely bleeding. The diagnostic yield was significantly higher in severe
      (72.73%) relative to moderate (32.41%) and mild bleeding (12.50%); P = 0.0001.
      Significantly more angioectasias were detected in severely bleeding patients
      (42.42%) than in those bleeding moderately (14.48%) and mildly (0.00%), P =
      0.0001. The ability of VCE to guide further intervention was significantly higher
      in patients bleeding severely (69.70%, P = 0.006). CONCLUSIONS: Our data showed a
      significant increase in diagnostic yield with the increasing degree of anemia.
      Relative difference in hemoglobin rather than absolute values may be a better
      predictor. The ability of VCE to guide further intervention reached significance
      in severely bleeding patients. The hypothesis that use of VCE prior to
      esophagogastroduodenoscopy or colonoscopy in the severely bleeding group deserves
      to be evaluated.

PMID- 21955429
TI  - Magnetic endoscopic imaging saves abdominal compression and patient pain in
      routine colonoscopies.
AB  - OBJECTIVE: Magnetic endoscope imaging (MEI) is a technique for the direct
      visualisation of endoscope configuration within the colon. This method may
      prevent loop formation by giving visual feedback of endoscope movement. This
      study aimed to evaluate the efficacy of MEI in improving colonoscopy performance.
      METHODS: Overall 1000 consecutive patients who underwent a complete routine
      colonoscopy were randomized into two groups: in group A with MEI, while in group
      B without MEI. Sedation was performed according to local standards. In both
      groups time to reach the cecum, the number of positioning maneuvers and
      involvement of a second assistant nurse were recorded. Abdominal compression was
      graded from 1 to 4 according to the duration and intensity of compression was
      quantified using a scale from 1-3 according to compression form and patient
      reaction. RESULTS: Patients were randomized (group A with MEI, n = 490; group B
      without MEI, n = 510) and a total colonoscopy was performed. Time to cecal
      intubation did not differ between the groups (507 s vs 538 s; NS). The duration
      of abdominal compression was significantly shorter in MEI guided colonoscopy. The
      intensity of abdominal compression was lower in group A and fewer turn maneuvers
      needed per patient. A trend towards a reduced need for assistance in MEI group
      was seen. CONCLUSION: Although MEI does not generally accelerate colonoscope
      advancement, it significantly reduces the force and the duration of abdominal
      compression by assistant personnel, thus minimizing patient discomfort and
      decreasing the need for additional staff.

PMID- 21955430
TI  - Epidemiological study of colorectal adenoma and cancer in symptomatic patients in
      China between 1990 and 2009.
AB  - OBJECTIVE: The best cure for colorectal cancer (CRC) lies on its early diagnosis
      and treatment. We aimed to provide the epidemiological features of advanced
      colorectal adenoma (A-CRA) and CRC in symptomatic patients and to determine
      whether the incidences of A-CRA and CRC increased simultaneously in China between
      1990 and 2009. METHODS: A total of 157,943 patients who had undergone a
      colonoscopy from 1990 to 2009 were enrolled, of which 6,777 patients had A-CRA
      and 3,503 had CRC. They were compared with controls in a stratified analysis. The
      detection rates of A-CRA and CRC in the 1990s and 2000s were also compared.
      RESULTS: The detection rate of A-CRA increased 1.88-fold over the two decades,
      while that of CRC increased 0.66-fold. The percentages of patients with A-CRA and
      CRC who were elder than 50 years were significantly higher in the 2000s than
      those in the 1990s (P = 0.000). The changes of location of A-CRA and CRC during
      the two decades indicated a shift of lesions from the distal colon to proximal
      colon. CONCLUSION: There was a significant increase in detection rate of A-CRA in
      the 2000s, but CRC did not increase at a similar speed. Our results indicated
      that the early detection and removal of colorectal adenoma in symptomatic
      patients might decrease the incidence of CRC.

PMID- 21955432
TI  - Economic burden attributable to functional bowel disorders in Iran: a cross
      sectional population-based study.
AB  - OBJECTIVE: While few population-based studies on the economic burden of
      functional bowel disorders (FBD) have been published from developing countries
      like Iran, this study aimed to estimate their direct and indirect costs for five
      groups of patients: irritable bowel syndrome (IBS), functional constipation (FC),
      unspecified-FBD (U-FBD), functional abdominal bloating (FAB) and functional
      diarrhea (FD). METHODS: Up to 18,180 adults randomly sampled from Tehran, Iran
      (2006-2007) were interviewed using two questionnaires based on the Rome III
      criteria to detect FBD patients and to estimate their medical expenses (such as
      visiting the doctor, drugs, hospitalization and laboratory tests) and
      productivity loss in the previous 6 months. All costs were converted to dollar
      purchasing power parity (PPP$) to facilitate cross-country comparisons. RESULTS:
      The mean total 6-month costs were approximately: 160, 147, 103, 96 and 42 PPP$
      for IBS, FC, U-FBD, FAB and FD, respectively. The highest proportion of drug
      consumption was found in IBS patients. The highest mean duration of absence from
      work was seen in IBS patients (2.26 days). Overall, doctor visit costs accounted
      for approximately 1/3 of the total costs for FBD, followed by hospitalization. A
      higher indirect cost of illness was found in IBS (54 PPP$), whereas it was zero
      in FD. CONCLUSION: The economic burden of FBD seems to be moderately high in Iran
      and it imposes a relatively heavy financial burden on the Iranian national health
      system because of its high prevalence and its impact on quality of life,
      productivity and waste of resources.

PMID- 21955431
TI  - Anti-nuclear antibody positivity and the use of certolizumab in inflammatory
      bowel disease patients who have had arthralgias or lupus-like reactions from
      infliximab or adalimumab.
AB  - OBJECTIVE: Tumor necrosis factor (TNF) inhibitors can be used to treat
      inflammatory bowel disease (IBD) but may lead to anti-nuclear antibody (ANA)
      positivity and lupus-like reactions. Because of its unique structure,
      certolizumab has lower rates of these complications. We sought to investigate
      whether patients who have had lupus-like reactions to infliximab or adalimumab
      would be able to tolerate certolizumab. METHODS: We performed a retrospective
      analysis on the 23 patients at the Roberts Inflammatory Bowel Disease Center who
      received certolizumab for the treatment of Crohn's disease from March 2008 to
      June 2009. We identified 6 patients who were switched to this drug because of
      lupus-like reactions from prior anti-TNF therapy and had documented ANA after the
      reaction and prior to certolizumab initiation. We then rechecked the ANA status
      after certolizumab initiation. RESULTS: Five out of 6 patients had a resolution
      of their arthralgias or lupus-like symptoms after being switched to certolizumab
      (P < 0.001). Of the 4 patients who were ANA positive after receiving infliximab
      or adalimumab, 2 became ANA negative after induction with certolizumab (P =
      0.17). There was no difference in Harvey Bradshaw index scores (10.3 vs. 9.8) pre
      certolizumab and post-certolizumab (P = 0.73). CONCLUSION: Nearly all patients
      experienced relief from their lupus-like symptoms with certolizumab and 2 out of
      4 patients reversed their ANA positivity. While future investigation is
      warranted, patients who have lupus-like reactions from infliximab or adalimumab
      may benefit from switching to certolizumab.

PMID- 21955433
TI  - Immunomodulation of inducible co-stimulator (ICOS) in human cytokine-induced
      killer cells against cholangiocarcinoma through ICOS/ICOS ligand interaction.
AB  - OBJECTIVE: To evaluate the immunomodulation of inducible co-stimulator (ICOS) in
      cytokine-induced killer (CIK) cells against cholangiocarcinoma. METHODS: CIK
      cells were generated from normal peripheral blood mononuclear cells. Methyl
      thiazolyl tetrazolium assay was performed to assess proliferation of CIK-ICOS and
      controlled CIK cells; ELISA was used to analyze the expression of cytokines.
      Reverse transcription-polymerase chain reaction and immunohistochemistry were
      performed to evaluate the expression of ICOS ligand (ICOSL) in CIK cells and
      human cholangiocarcinoma cell line QBC939 cells. The cytotoxicity of CIK cells
      was determined either by lactate dehydrogenase-releasing assay in vivo or
      alteration of tumor size prior to and after the treatment of CIK cells in vivo.
      RESULTS: CIK-ICOS cells proliferated more and expressed higher secretion a level
      of interferon-gamma than the controlled CIK. These cells exhibited higher
      cytotoxicity against cholangiocarcinoma cell lines at all efficacy: toxicity
      (E:T) ratios tested than the controlled CIK cells. More importantly, the anti
      ICOSL antibody was able to attenuate the elevated cytotoxicity mediated by ICOS
      overexpression. When injected into cholangiocarcinoma xenografts in severe
      combined immunodeficiency mice, CIK-ICOS cells survived better than the
      controlled CIK cells around xenografts and significantly reduced the growth rate
      of cholangiocarcinoma, with least volume increase and more severe necrosis of the
      xenografts than controlled mice treated with saline, CIK or CIK-enhanced green
      fluorescent protein. CONCLUSION: ICOS can enhance the cytotoxic effect of CIK
      cells against cholangiocarcinoma both in vitro and in vivo. This effect is
      mediated by ICOS-augmented cytokine secretion and cell proliferation, and in part
      through ICOS-ICOSL interaction.

PMID- 21955434
TI  - Differentiation between pancreatic carcinoma and mass-forming chronic
      pancreatitis: usefulness of high b value diffusion-weighted imaging.
AB  - OBJECTIVE: To investigate the value of high b value diffusion-weighted (DW)
      imaging in differentiating between pancreatic carcinoma and mass-forming chronic
      pancreatitis (MFCP). METHODS: Fifty-one consecutive patients with pathology
      proven pancreatic carcinoma (n = 37) or MFCP (n = 14) were evaluated with DW
      imaging (b value, 0 and 1000 s/mm(2)) at a 3-T MR system. Overall 20 healthy
      volunteers were evaluated as the control group. The apparent diffusion
      coefficient (ADC) values of normal pancreas, pancreatic carcinoma, MFCP, and mass
      associated obstructive pancreatitis were measured. RESULTS: On high b value (1000
      s/mm(2) ) DW images, both pancreatic carcinoma and MFCP were hyperintense focal
      lesions; mass-associated obstructive pancreatitis occurred in 17 of 37 (45.9%)
      pancreatic carcinoma and 8 of 14 (57.1%) MFCP. The ADC (*10(-3) mm(2) /s) of the
      pancreatic carcinomas (1.06 +/- 0.15) was significantly lower than that of normal
      pancreas (1.47 +/- 0.18; P < 0.01), MFCP (1.35 +/- 0.14; P < 0.01) and mass
      associated chronic pancreatitis (1.44 +/- 0.17; P < 0.01). The ADC of MFCP was
      also lower than that in the normal pancreas (P = 0.025), whereas the ADC of mass
      associated obstructive pancreatitis was not different from those of the MFCP (P =
      0.113) and normal pancreas (P = 0.544). When 1.195 was used as the optimal cut
      off value, ADC quantification obtained a sensitivity of 85.7% and a specificity
      of 86.5% for differentiating pancreatic carcinomas from MFCP. CONCLUSION: High b
      value DW imaging in combination with ADC quantification at a 3-T MR system is
      useful in differentiating between pancreatic carcinoma and MFCP.

PMID- 21955435
TI  - Case report of HFE gene testing for the diagnosis of hereditary hemochromatosis.

PMID- 21955436
TI  - Subcapsular liver biloma due to gallbladder perforation after acute
      cholecystitis.

PMID- 21955438
TI  - Evolution and diversity of community-associated methicillin-resistant
      Staphylococcus aureus in a geographical region.
AB  - BACKGROUND: Community-associated methicillin-resistant Staphylococcus aureus (CA
      MRSA) was first reported in remote regions of Western Australia and is now the
      predominant MRSA isolated in the state. The objective of this study is to
      determine the genetic relatedness of Western Australian CA-MRSA clones within
      different multilocus sequence type (MLST) clonal clusters providing an insight
      into the frequency of S. aureus SCCmec acquisition within a region. RESULTS: The
      CA-MRSA population in Western Australia is genetically diverse consisting of 83
      unique pulsed-field gel electrophoresis strains from which 46 MLSTs have been
      characterised. Forty five of these sequence types are from 18 MLST clonal
      clusters and two singletons. While SCCmec IV and V are the predominant SCCmec
      elements, SCCmec VIII and several novel and composite SCCmec elements are
      present. The emergence of MRSA in diverse S. aureus clonal clusters suggests
      horizontal transmission of the SCCmec element has occurred on multiple occasions.
      Furthermore DNA microarray and spa typing suggests horizontal transfer of SCCmec
      elements has also occurred within the same CC. For many single and double locus
      variant CA-MRSA clones only a few isolates have been detected. CONCLUSIONS:
      Although multiple CA-MRSA clones have evolved in the Western Australian community
      only three clones have successfully adapted to the Western Australian community
      environment. These data suggest the successful evolution of a CA-MRSA clone may
      not only depend on the mobility of the SCCmec element but also on other genetic
      determinants.

PMID- 21955439
TI  - Neural response to experimental heat pain in stable patients with schizophrenia.
AB  - Diminished pain sensitivity in schizophrenia has been reported in clinical
      studies. While the role of antipsychotic medications as a cause of the decrease
      in pain perception has been questioned, little is known about neural pain
      processing in treated schizophrenia patients. The aim of this pilot study was to
      examine the blood oxygen level-dependent (BOLD) changes induced by an
      experimental pain tolerance (endure) hot stimuli vs. non-painful stimuli in
      clinically stable patients with schizophrenia and in healthy controls. Twelve
      patients with schizophrenia, treated with risperidone and considered clinically
      stable, and 13 gender- and age-matched healthy controls were studied using
      painful and non-painful thermal stimuli in a periodic block design. BOLD changes
      were assessed using high field, 3 T functional Magnetic Resonance Imaging (fMRI).
      Pain tolerance in stable patients was not statistically different than healthy
      controls. Interestingly, patients showed higher activation in the primary
      somatosensory cortex (S1) and superior prefrontal cortex, and less activation in
      the posterior cingulate cortex and brainstem than controls. Our pilot study
      indicates that pain tolerance is similar in clinically stable patients and
      controls, although the neural processing of pain is not normalized with
      antipsychotic treatment.

PMID- 21955440
TI  - Ranavirus-associated mass mortality in wild amphibians, the Netherlands, 2010: a
      first report.
AB  - In 2010, a mass die-off of over 1000 wild water frogs (Pelophylax spp.) and at
      least 10 common newts (Lissotriton vulgaris) occurred in a pond in The
      Netherlands. Haemorrhagic disease with hepatomegaly and splenomegaly was evident.
      Microscopically, multiple organs presented cells with multifocal intracytoplasmic
      inclusion bodies, in which ranavirus-like particles were demonstrated
      ultrastructurally. All specimens examined tested positive for ranavirus by PCR.
      The sequence obtained showed a 100% identity with the one deposited for common
      midwife toad virus (CMTV). This is the first report of ranavirus-associated
      mortality in wild amphibian populations in The Netherlands. It is also the first
      time CMTV or a CMTV-like virus has been reported in these two species in the
      adult stage and outside of Spain.

PMID- 21955441
TI  - Investigation of serology for diagnosis of outbreaks of botulism in cattle.
AB  - Serology has been used to diagnose retrospectively types C and D outbreaks of
      botulism in cattle in Australia and this study has investigated whether the
      approach would be applicable in England and Wales. Three hundred sera from
      routine surveillance submissions in England and Wales were used as a negative
      control population. Some stored sera were available from a small number of
      clinical cases of botulism and 125 samples were collected from cohort groups of
      clinical cases in four new outbreaks of botulism. Three of these outbreaks were
      identified as being caused by type D Clostridium botulinum toxin. Sera were
      tested by antibody ELISA in laboratories in Australia and Germany. There was no
      increase in the proportion of animals seropositive to type C or D antibody in the
      botulism-associated cattle. The proportion of samples which were seropositive to
      type D antibodies was <2% in both the negative control and outbreak populations.
      It was concluded that single time serology is unlikely to be helpful for
      retrospective diagnosis of outbreaks of type D botulism in England and Wales.

PMID- 21955442
TI  - A review of midwifery education curriculum documents in Jordan.
AB  - BACKGROUND: There is worldwide recognition that midwives are specialists in
      normal pregnancy, labour and birth and the postnatal period and that they should
      be educated to be primary providers of maternity care. In Jordan midwives
      currently have limited opportunities to fulfil this role. Since the mid-1980s,
      two public community colleges have offered three-year diploma midwifery education
      programmes in two major cities in Jordan. In 2002 the first and only four-year
      bachelor of midwifery education programme was established in one public
      university. AIM: A review to describe the design and content of midwifery
      education programmes in Jordan and address the question: Does the design of
      midwifery education programmes in Jordan encourage confidence that graduates will
      be competent to practise to the full capacity of the internationally defined role
      and scope of practice of the midwife and undertake the role of primary maternity
      care providers for women with low-risk pregnancies? DESIGN: A review of Jordanian
      midwifery education curriculum documents was undertaken using information and
      documents provided by midwifery programme coordinators. PARTICIPANTS: Programme
      coordinators in all institutions in Jordan providing midwifery education
      programmes. FINDINGS: The curriculum documents reflected a medical model, with an
      emphasis on illness and intervention rather than preparation for the
      internationally defined full role and scope of practice of the midwife.
      IMPLICATIONS FOR PRACTICE: This study provides a profile of midwifery education
      curriculum documents in Jordan with recommendations for changes that would
      position midwives as potential primary maternity care providers for women in
      Jordan who have uncomplicated pregnancies.

PMID- 21955443
TI  - Host-response patterns of intramammary infections in dairy cows.
AB  - Many different bacterial species have the ability to cause an infection of the
      bovine mammary gland and the host response to these infections is what we
      recognize as mastitis. In this review we evaluate the pathogen specific response
      to the three main bacterial species causing bovine mastitis: Escherichia coli,
      Streptococcus uberis and Staphylococcus aureus. In this paper we will review the
      bacterial growth patterns, host immune response and clinical response that
      results from the intramammary infections. Clear differences in bacterial growth
      pattern are shown between bacterial species. The dominant pattern in E. coli
      infections is a short duration high bacteria count infection, in S. aureus this
      is more commonly a persistent infection with relative low bacteria counts and in
      S. uberis a long duration high bacteria count infection is often observed. The
      host immune response differs significantly depending on the invading bacterial
      species. The underlying reasons for the differences and the resulting host
      response are described. Finally we discuss the clinical response pattern for each
      of the three bacterial species. The largest contrast is between E. coli and S.
      aureus where a larger proportion of E. coli infections cause potentially severe
      clinical symptoms, whereas the majority of S. aureus infections go clinically
      unnoticed. The relevance of fully understanding the bovine host response to
      intramammary infection is discussed, some major gaps in our knowledge are
      highlighted and directions for future research are indicated.

PMID- 21955444
TI  - Molecular structure and characterization of the cytokine TWEAK and its receptor
      Fn14 in bovine.
AB  - Full-length cDNA encoding TWEAK and Fn14 from bovine was isolated. We used
      bioinformatics to analyze the gene structure, function, evolutionary
      relationships, and predicted three-dimensional structure of proteins and binding
      sites. Real-time quantitative PCR (Q-PCR) analysis revealed that both TWEAK and
      Fn14 are constitutively expressed in various tissues in bovine. Bovine TWEAK and
      Fn14 interaction analysis by yeast two-hybrid. Our results suggest that the TWEAK
      Fn14 pathway is evolutionarily highly conserved. It will be helpful for
      investigation on the biological role of the TWEAK/Fn14 system in this important
      animal model. Furthermore, it provides insight into the molecular evolution of
      the emerging TWEAK and Fn14 families.

PMID- 21955445
TI  - Induction, regulation and physiological role of IL-17 secreting helper T-cells
      isolated from PBMC, thymus, and lung lymphocytes of young pigs.
AB  - Interleukin-17 (IL-17) producing cells, referred to as Th17, have recently
      emerged as a third subset of the T helper (Th) cell family. Studies in mice have
      demonstrated that Th17 cells and their associated cytokines are involved in
      several autoimmune diseases and host defense against infection. Murine Th17 cells
      differentiate from naive CD4(+) T-cells in the presence of TGFbeta and IL-6,
      however, there are contradicting reports as to the role of TGFbeta in the
      differentiation of human Th17 cells and very little is known about these cells in
      other animals. We report here the presence of IL-17 secreting lymphocytes in the
      lung and peripheral blood of pigs. The cDNA of porcine IL-17 gene was cloned and
      sequenced from activated lung lymphocytes and PBMC from piglets. A 17kDa
      recombinant protein was expressed and purified both under denaturing and native
      conditions from E. coli BL21 cells. Furthermore, we demonstrate that TGFbeta in
      the presence of IL-6 and/or IL-1beta induces in vitro differentiation of Th17
      cells from naive porcine CD4(+) thymocytes.

PMID- 21955446
TI  - Food allergen-specific serum IgG and IgE before and after elimination diets in
      allergic dogs.
AB  - Serum food allergen-specific antibody testing is widely offered to identify
      suitable ingredients for diets to diagnose adverse food reaction (AFR) in dogs
      with allergic skin disease. Antibody concentrations in blood samples obtained
      during an unsuccessful diet to help in the choice of diet changes may be
      influenced by the previous diet. The objective of this paper was to measure food
      antigen-specific IgE and IgG for the most commonly used 16 food antigens before
      and after an elimination diet. Levels of food-specific serum IgE and IgG
      antibodies were measured by enzyme-linked immunosorbent assay (ELISA). Dogs had
      detectable IgE antibodies to beef, pork, lamb and cows' milk; and detectable IgG
      antibodies to beef, pork, lamb, cows' milk, chicken and turkey. Of 19 dogs with
      complete data sets, 14 dogs showed clear improvement during diet and in 7 dogs
      AFR could be diagnosed by deterioration on rechallenge and subsequent improvement
      on refeeding the diet. Serum was obtained before and 6-8 weeks after beginning
      such a diet. There was no significant difference in pre- and post-diet levels for
      any of the individual allergens nor for the total IgE and IgG concentrations of
      all antigens (P=0.55 and P=0.53 respectively). In these 19 dogs in which an
      elimination diet was used for the diagnosis of food allergy and in which 14 were
      probably food allergic and 7 were proven food allergic there were no significant
      differences in food-specific antibodies before and after an elimination diet of 6
      8 weeks.

PMID- 21955447
TI  - Experimental infection of cattle, sheep and pigs with 'Hobi'-like pestivirus.
AB  - To date, limited information is available on the ability of 'Hobi'-like
      pestiviruses (putative bovine viral diarrhoea 3) to infect and cause disease in
      animal species traditionally affected by pestiviruses. In order to obtain new
      insights into host range and pathogenic potential of this atypical pestivirus,
      BVDV-seronegative calves (n=5), lambs (n=5) and piglets (n=5) were experimentally
      infected with the European 'Hobi'-like strain Italy-1/10-1, whereas two animals
      per species served as uninfected controls. Appearance of clinical signs,
      leukopenia, viremia, viral shedding and seroconversion were monitored for 28 days
      post-infection. Calves and lambs were successfully infected, displaying
      respiratory signs (nasal discharge), moderate hyperthermia and leukopenia,
      viremia and viral shedding through the nasal and faecal routes. Antibody
      responses were observed in both animal species by ELISA and virus neutralisation
      assays. In contrast, inoculated piglets did not display any clinical signs nor
      leukopenia and viral RNA was not detected in any biological samples.
      Nevertheless, the presence of detectable antibodies by virus neutralisation
      accounted for a successful, albeit limited infection of these animals.

PMID- 21955448
TI  - Isolation and characterization of Ochrobactrum anthropi and Ochrobactrum pecoris
      from caecal content of commercial turkeys.
AB  - Two Gram negative, micro-aerophilic, non-motile and non-spore-forming coccoid
      bacteria were isolated from female turkey caecal samples collected from a
      slaughterhouse. The biochemical reaction profiles (API 20 E and API 20 NE) typed
      both strains as Ochrobactrum anthropi. On the basis of 16S rRNA gene and recA
      gene sequence similarities the strains were identified as O. anthropi and
      Ochrobactrum pecoris, respectively. Both strains were highly resistant against
      beta-lactam antibiotics, chloramphenicol and sulphonamides but variable in
      susceptibility to ciprofloxacin, gentamicin and tetracycline. This is the first
      time that Ochrobactrum species were isolated from an avian host, i.e. turkey.

PMID- 21955449
TI  - Genetic relationship of H3 subtype avian influenza viruses isolated from domestic
      ducks and wild birds in Korea and their pathogenic potential in chickens and
      ducks.
AB  - The H3 subtype avian influenza virus (AIV) is one of the most frequently isolated
      subtypes in domestic ducks, live poultry markets, and wild birds in Korea. In
      2002-2009, a total of 45 H3 subtype AIVs were isolated from the feces of
      clinically normal domestic ducks (n=28) and wild birds (n=17). The most prevalent
      subtypes in domestic ducks were H3N2 (35.7%), H3N6 (35.7%), H3N8 (25.0%), and
      H3N1 (3.6%, novel subtype in domestic duck in Korea). In contrast, H3N8 (70.6%)
      is the most prevalent subtype in wild birds in Korea. In the phylogenetic
      analysis, HA genes of the Korean H3 AIVs were divided into 3 groups (Korean duck,
      wild bird 1, and wild bird 2) and all viruses of duck origin except one were
      clustered in a single group. However, other genes showed extensive diversity and
      at least 17 genotypes were circulating in domestic ducks in Korea. When the
      analysis expanded to viruses of wild bird origin, the genetic diversity of Korean
      H3 AIVs became more complicated. Extensive reassortments may have occurred in H3
      subtype influenza viruses in Korea. When we inoculated chickens and ducks with
      six selected viruses, some of the viruses replicated efficiently without pre
      adaptation and shed a significant amount of viruses through oropharyngeal and
      cloacal routes. This raised concerns that H3 subtype AIV could be a new subtype
      in chickens in Korea. Continuous surveillance is needed to prepare the advent of
      a novel subtype AIV in Korea.

PMID- 21955450
TI  - Impaired activities of cyclic adenosine monophosphate-responsive element binding
      protein, protein kinase A and calcium-independent phospholipase A2 are involved
      in deteriorated regeneration of cirrhotic liver after partial hepatectomy in
      rats.
AB  - AIMS:   This study is to elucidate whether cyclic adenosine monophosphate (cAMP)
      mediated signal is involved in lower regenerative potential of cirrhotic liver.
      METHODS:   Hepatic cAMP concentration, activities of protein kinase A (PKA), c
      AMP responsive element binding protein (CREB) and Ca(2+) -independent
      phospholipase A(2)  (iPLA2) and regeneration rate were compared between rats with
      thioacetamide-induced cirrhotic and normal livers after two-third hepatectomy.
      RESULTS:   The liver regeneration estimated by the rates of [(3) H]-thymidine
      incorporation and staining of proliferating cell nuclear antigen was
      significantly lower in the cirrhotic group. CREB, PKA and iPLA2 activities,
      assessed by western blots and electromobility shift assay, were significantly
      impaired after hepatectomy in the cirrhosis group. PKA and iPLA2 silencing by
      siRNA transfection significantly inhibited CREB activity and cell growth in
      transformed hepatocytes in vitro. CONCLUSIONS:   CREB dysfunction, mediated by
      PKA and iPLA2 suppression, may be involved in the deteriorated liver regeneration
      in the cirrhotic rats.

PMID- 21955451
TI  - Be known, be available, be mutual: a qualitative ethical analysis of social
      values in rural palliative care.
AB  - BACKGROUND: Although attention to healthcare ethics in rural areas has increased,
      specific focus on rural palliative care is still largely under-studied and under
      theorized. The purpose of this study was to gain a deeper understanding of the
      values informing good palliative care from rural individuals' perspectives.
      METHODS: We conducted a qualitative ethnographic study in four rural communities
      in Western Canada. Each community had a population of 10, 000 or less and was
      located at least a three hour travelling distance by car from a specialist
      palliative care treatment centre. Data were collected over a 2-year period and
      included 95 interviews, 51 days of field work and 74 hours of direct participant
      observation where the researchers accompanied rural healthcare providers. Data
      were analyzed inductively to identify the most prevalent thematic values, and
      then coded using NVivo. RESULTS: This study illuminated the core values of
      knowing and being known, being present and available, and community and mutuality
      that provide the foundation for ethically good rural palliative care. These
      values were congruent across the study communities and across the stakeholders
      involved in rural palliative care. Although these were highly prized values, each
      came with a corresponding ethical tension. Being known often resulted in a loss
      of privacy. Being available and present created a high degree of expectation and
      potential caregiver strain. The values of community and mutuality created
      entitlement issues, presenting daunting challenges for coordinated change.
      CONCLUSIONS: The values identified in this study offer the opportunity to better
      understand common ethical tensions that arise in rural healthcare and key
      differences between rural and urban palliative care. In particular, these values
      shed light on problematic health system and health policy changes. When
      initiatives violate deeply held values and hard won rural capacity to address the
      needs of their dying members is undermined, there are long lasting negative
      consequences. The social fabric of rural life is frayed. These findings offer one
      way to re-conceptualize healthcare decision making through consideration of
      critical values to support ethically good palliative care in rural settings.

PMID- 21955452
TI  - Meticillin resistance in orthopaedic coagulase-negative staphylococcal
      infections.
AB  - Orthopaedic infections due to coagulase-negative staphylococci (CoNS) and
      meticillin-resistant strains may be increasing. We assessed secular trends of
      CoNS infections and factors associated with meticillin resistance by performing a
      13-year retrospective cohort study of orthopaedic patients with CoNS infections
      from January 1995 to December 2007. Of 60 CoNS infections, 57 (95%) were implant
      related. Median follow-up after end of treatment was 5.1 years (range: 2.4-13.8).
      During the study period, 44,237 orthopaedic procedures were performed, 21,299
      (48%) with implants. The overall cumulative incidence of CoNS-associated
      infection was 0.14% and 0.28% for implant-related procedures. There were non
      significant changes in the absolute number or cumulative incidence of CoNS
      infection (chi-squared test, P values for trend: 0.45 and 0.97, respectively).
      Forty-five episodes (75%) were due to meticillin-resistant strains. The
      proportion of meticillin resistance remained stable over time (P for trend:
      0.65). Whereas few (4/15) meticillin-susceptible strains were associated with
      prior prophylaxis that covered the causative pathogen, 28/45 meticillin-resistant
      strains were associated with inadequate prophylaxis (P=0.03). The cumulative
      incidence of orthopaedic CoNS infection is low and stable in our institution and
      almost exclusively implant-related. The proportion of meticillin resistance among
      CoNS has remained stable over the last decade with a favourable clinical outcome.

PMID- 21955453
TI  - Epidemiology and costs associated with norovirus outbreaks in NHS Lothian,
      Scotland 2007-2009.
AB  - Healthcare-associated gastroenteritis outbreaks are becoming more common and are
      recognized challenges in hospital and community settings. In Edinburgh [NHS
      (National Health Service) Lothian], all the hospitals and the community were
      actively monitored for outbreaks of gastroenteritis from September 2007 to June
      2009. In total, 1732 patients and 599 healthcare staff were affected in 192 unit
      outbreaks. In the acute sector, 1368 patients (0.99 cases/1000 inpatient bed
      days) and 406 healthcare staff (0.29 cases/1000 inpatient bed-days) were affected
      in 155 unit outbreaks (0.23 unit outbreaks/day). Noroviruses were detected in 142
      outbreaks (74%); 50 were not laboratory confirmed but were presumed to be
      noroviruses on epidemiological grounds. The closure of affected units to new
      admissions resulted in the loss of 3678 bed-days. By extrapolation, lost bed-days
      and staff absence due to gastroenteritis outbreaks cost NHS Lothian L1.2 million
      for the two norovirus seasons. Outbreaks in which the affected unit was closed
      within the first three days of recognizing the index case were contained in a
      mean of six days, and outbreaks in units that were closed later persisted for a
      mean of seven days; this difference was not statistically significant. Rapid
      implementation of control measures was effective in the control of outbreaks.

PMID- 21955454
TI  - 1,1-Diarylalkenes as anticancer agents: dual inhibitors of tubulin polymerization
      and phosphodiesterase 4.
AB  - A series of 1,1-diarylalkene derivatives were prepared to optimize the properties
      of CC-5079 (1), a dual inhibitor of tubulin polymerization and phosphodiesterase
      4 (PDE4). By using the 3-ethoxy-4-methoxyphenyl PDE4 pharmacophore as one of the
      aromatic rings, a significant improvement in PDE4 inhibition was achieved.
      Compound 28 was identified as a dual inhibitor with potent PDE4 (IC(50)=54 nM)
      and antitubulin activity (HCT-116 IC(50)=34 nM and tubulin polymerization IC(50)
      ~1 MUM). While the nitrile group at the alkene terminus was generally required
      for potent antiproliferative activity, its replacement was tolerated if there was
      a hydroxyl or amino group on one of the aryl rings. Conveniently, this group
      could also serve as a handle for amino acid derivatization to improve the
      compounds' solubility. The glycinamide analog 45 showed significant efficacy in
      the HCT-116 xenograft model, with 64% inhibition of tumor growth upon dosing at
      20 mg/kg qd.

PMID- 21955455
TI  - Tocotrienamines and tocopheramines: reactions with radicals and metal ions.
AB  - The antioxidant activity of vitamin E (VE) homologs alpha, gamma and delta
      tocotrienamines (4b-6b), never studied before, and alpha, gamma and delta
      tocopheramines (4a-7a) was investigated by means of different total antioxidant
      capacity (TAC) tests. In all the test model systems, compounds 4a-7a and 4b-6b
      showed similar or higher TAC values than the parental vitamin E forms and their
      physiological metabolites. alpha-Homologs of VE amines showed markedly higher
      activity than the VE congeners in the TEAC test, which is tailored for
      liposoluble antioxidants, while gamma-homologs of the amine analogs showed higher
      activity in the FRAP tests. Kinetics analysis of the reaction with DPPH(.) showed
      higher second order rate k for 4a than for alpha-tocopherol (1a). alpha
      Tocopherolquinone 1f was the common main oxidation product for both 1a and alpha
      tocopheramine (4a) exposed to ferric ions or DPPH(.), and the implied oxidative
      deamination of 4a was accompanied by a nitration reaction of phenolic substrates
      that were added to the reaction medium. Possible mechanisms of these reactions
      were studied.

PMID- 21955456
TI  - Three-dimensional quantitative structure-activity relationship analyses of
      substrates of the human proton-coupled amino acid transporter 1 (hPAT1).
AB  - The proton-coupled amino acid transporter hPAT1 has recently gained much interest
      due to its ability to transport small drugs thereby allowing their oral
      administration. A three-dimensional quantitative structure-activity relationship
      (3D QSAR) study has been performed on its natural and synthetic substrates
      employing comparative molecular similarity indices analysis (CoMSIA) to
      investigate the structural requirements for substrates and to derive a predictive
      model that may be used for the design of new prodrugs. The cross-validated CoMSIA
      models have been derived from a training set of 40 compounds and the predictive
      ability of the resulting models has been evaluated against a test set of 10
      compounds. Despite the relatively narrow range of binding affinities (K(i)
      values) reliable statistical models with good predictive power have been
      obtained. The best CoMSIA model in terms of a proper balance of all statistical
      terms and the overall contribution of individual properties has been obtained by
      considering steric, hydrophobic, hydrogen bond donor and acceptor descriptors
      (q(cv)(2)=0.683, r(2)=0.958 and r(PRED)(2)=0.666). The 3D QSAR model provides
      insight in the interactions between substrates and hPAT1 on the molecular level
      and allows the prediction of affinity constants of new compounds. A pharmacophore
      model has been generated from the training set by means of the MOE (molecular
      operating environment) program. This model has been used as a query for virtual
      screening to retrieve potential new substrates from the small-molecule, 'lead
      like' databases of MOE. The affinities of the compounds were predicted and 11
      compounds were identified as possible high-affinity substrates. Two selected
      compounds strongly inhibited the hPAT mediated l-[(3)H]proline uptake into Caco-2
      cells constitutively expressing the transport protein.

PMID- 21955457
TI  - Diffusion tensor imaging in Alzheimer's disease and dementia with Lewy bodies.
AB  - White matter changes have been investigated in Alzheimer's disease (AD) in a
      number of studies using diffusion imaging. Fewer studies have investigated
      dementia with Lewy bodies (DLB). We used diffusion-weighted magnetic resonance
      imaging (MRI) and high-resolution (0.3 mm in-plane) coronal 3T MRI of the medial
      temporal lobe in 16 subjects with AD, 16 with DLB and 16 similarly aged healthy
      subjects. We found increased mean diffusivity in the temporal lobe of AD, and
      reduced fractional anisotropy (FA) in a small cluster in the right postcentral
      gyrus region in the DLB group. Mean FA in this cluster correlated with UPDRS
      (Unified Parkinson's Disease Rating Scale) motor score. We had previously
      reported reduced visibility in the AD group of a dark appearing layer of the
      hippocampus in the high-resolution images. In an SPM analysis on all subjects,
      there were significant clusters of reduced FA in the corpus callosum, fornix and
      stria terminalis that correlated with the visual rating of the hippocampus. These
      results suggest that changes to the hippocampus are associated with structural
      changes to the white matter fibres of the hippocampus output, and that changes in
      motor function are associated with changes in white matter underlying
      somatosensory cortex.

PMID- 21955458
TI  - Characterization of the chipsi subcomplex of Pseudomonas aeruginosa DNA
      polymerase III.
AB  - BACKGROUND: DNA polymerase III, the main enzyme responsible for bacterial DNA
      replication, is composed of three sub-assemblies: the polymerase core, the beta
      sliding clamp, and the clamp loader. During replication, single-stranded DNA
      binding protein (SSB) coats and protects single-stranded DNA (ssDNA) and also
      interacts with the chipsi heterodimer, a sub-complex of the clamp loader. Whereas
      the chi subunits of Escherichia coli and Pseudomonas aeruginosa are about 40%
      homologous, P. aeruginosa psi is twice as large as its E. coli counterpart, and
      contains additional sequences. It was shown that P. aeruginosa chipsi together
      with SSB increases the activity of its cognate clamp loader 25-fold at low salt.
      The E. coli clamp loader, however, is insensitive to the addition of its cognate
      chipsi under similar conditions. In order to find out distinguishing properties
      within P. aeruginosa chipsi which account for this higher stimulatory effect, we
      characterized P. aeruginosa chipsi by a detailed structural and functional
      comparison with its E. coli counterpart. RESULTS: Using small-angle X-ray
      scattering, analytical ultracentrifugation, and homology-based modeling, we found
      the N-terminus of P. aeruginosa psi to be unstructured. Under high salt
      conditions, the affinity of the chipsi complexes from both organisms to their
      cognate SSB was similar. Under low salt conditions, P. aeruginosa chipsi,
      contrary to E. coli chipsi, binds to ssDNA via the N-terminus of psi. Whereas it
      is also able to bind to double-stranded DNA, the affinity is somewhat reduced.
      CONCLUSIONS: The binding to DNA, otherwise never reported for any other psi
      protein, enhances the affinity of P. aeruginosa chipsi towards the SSB/ssDNA
      complex and very likely contributes to the higher stimulatory effect of P.
      aeruginosa chipsi on the clamp loader. We also observed DNA-binding activity for
      P. putida chipsi, making this activity most probably a characteristic of the psi
      proteins from the Pseudomonadaceae.

PMID- 21955459
TI  - The role of the kidneys in glucose homeostasis: a new path towards normalizing
      glycaemia.
AB  - The maintenance of normal glucose homeostasis requires a complex, highly
      integrated interaction among the liver, muscle, adipocytes, pancreas and
      neuroendocrine system. Recent studies have showed that the kidneys also play a
      central role in glucose homeostasis by reabsorbing all the filtered glucose, an
      adaptive mechanism that ensures sufficient energy is available during fasting
      periods. This mechanism becomes maladaptive in diabetes, however, as
      hyperglycaemia augments the expression and activity of the sodium-glucose
      cotransporter (SGLT) 2 in the proximal tubule of the kidney. As a result, glucose
      reabsorption may be increased by as much as 20% in individuals with poorly
      controlled diabetes. SGLT2 is a low-affinity, high-capacity glucose transport
      protein that reabsorbs 90% of filtered glucose, while the high-affinity, low
      capacity SGLT1 transporter reabsorbs the remaining 10%. SGLT2 represents a novel
      target for the treatment of diabetes. In animal studies, SGLT2 inhibition reduces
      plasma glucose levels, resulting in improved beta-cell function and enhanced
      insulin sensitivity in liver and muscle. Human studies have confirmed the
      efficacy of SLGT2 inhibitors in improving glucose control and reducing the A1c.
      Because the mechanism of SGLT2 inhibition is independent of circulating insulin
      levels or insulin sensitivity, these agents can be combined with all other
      antidiabetic classes, including exogenous insulin. Although the long-term
      efficacy and safety of SGLT2 inhibitors remain under study, the class represents
      a novel therapeutic approach with potential for the treatment of both type 2 and
      1 diabetes.

PMID- 21955460
TI  - Reduced clot strength upon admission, evaluated by thrombelastography (TEG), in
      trauma patients is independently associated with increased 30-day mortality.
AB  - INTRODUCTION: Exsanguination due to uncontrolled bleeding is the leading cause of
      potentially preventable deaths among trauma patients. About one third of trauma
      patients present with coagulopathy on admission, which is associated with
      increased mortality and will aggravate bleeding in a traumatized patient.
      Thrombelastographic (TEG) clot strength has previously been shown to predict
      outcome in critically ill patients. The aim of the present study was to
      investigate this relation in the trauma setting. METHODS: A retrospective study
      of trauma patients with an injury severity qualifying them for inclusion in the
      European Trauma Audit and Research Network (TARN) and a TEG analysis performed
      upon arrival at the trauma centre. RESULTS: Eighty-nine patients were included.
      The mean Injury Severity Score (ISS) was 21 with a 30-day mortality of 17%.
      Patients with a reduced clot strength (maximal amplitude < 50 mm) evaluated by
      TEG, presented with a higher ISS 27 (95% CI, 20-34) vs. 19 (95% CI, 17-22), p =
      0.006 than the rest of the cohort. Clot strength correlated with the amount of
      packed red blood cells (p = 0.01), fresh frozen plasma (p = 0.04) and platelet
      concentrates (p = 0.03) transfused during the first 24 hours of admission.
      Patients with low clot strength demonstrated increased 30-day mortality (47% vs.
      10%, p < 0.001). By logistic regression analysis reduced clot strength was an
      independent predictor of increased mortality after adjusting for age and ISS.
      CONCLUSION: Low clot strength upon admission is independently associated with
      increased 30-day mortality in trauma patients and it could be speculated that
      targeted interventions based on the result of the TEG analysis may improve
      patient outcome. Prospective randomized trials investigating this potential are
      highly warranted.

PMID- 21955461
TI  - Practice guidelines for bone-anchored hearing aids in children.
AB  - After more than 20 years of clinical experience in children, bone-anchored
      hearing aids, essentially BAHA((r)), have become the standard treatment for
      conductive or mixed hearing loss. Based on a general review of the literature and
      the authors' own experience, this article reviews the use of bone-anchored
      hearing aids in children. The main indications for bone-anchored hearing aids are
      a minimum age of 5 years at the time of implantation and/or cortical bone
      thickness >= 3 mm. Fixture loss is observed in 40% of children under the age of 5
      years versus 8% for children aged 5 to 10 years and 1% for children over the age
      of 10 years, i.e. identical to the rate observed in adults. Skin complications
      are similar to those observed in adults and must be prevented by parental
      education and regular follow-up. Surgery is generally performed in two stages or
      as a one-stage procedure for fixtures >= 4 mm. The functional success rate,
      correlated with medium- and long-term use of BAHA((r)) is about 96%. BAHA((r))
      may be indicated in children with profound unilateral hearing loss following a
      trial period wearing a BAHA((r)) headband for several weeks with the child's
      active participation. Sequential bilateral implantation requires complementary
      investigations and appears to provide improved perception in noise. This type of
      hearing aid provides an improvement of the quality of life of children with
      bilateral conductive and/or mixed hearing loss which should be further improved
      as a result of recent technical developments.

PMID- 21955462
TI  - Outpatient tonsillectomy in children: a 7-year experience.
AB  - OBJECTIVES: To report our centre's experience of outpatient tonsillectomy in
      children over a 7-year period and to evaluate the postoperative complication rate
      in this type of procedure compared to tonsillectomy performed in the context of
      conventional hospitalisation. MATERIAL AND METHODS: Retrospective review of
      medical charts. RESULTS: From May 2002 to April 2009, 276 tonsillectomies were
      performed on an outpatient basis, i.e. 55.4% of all paediatric tonsillectomies,
      in children with a mean age of 5.28 years. Ninety-six children (34.8%) presented
      clinical OSAS. Development of an early postoperative complication (before H8)
      required conventional hospitalisation on D0 in six (2.1%) of these 276 children
      operated on an outpatient basis: early postoperative bleeding in four cases
      (1.4%), which required reoperation to control bleeding in three cases, refusal to
      feed in one case (0.3%), and a parental problem in one case (0.3%). Postoperative
      complications occurring after H8 required readmission in six cases (2.1%): pain
      and feeding difficulties in two cases (0.7%) on D1 and D5, respectively, bleeding
      in four cases (1.4%) with reoperation before H24 for one patient, D5 for two
      patients and D7 for one patient. Only one case of bleeding occurred between H8
      and H24. No perioperative respiratory complications were observed in children
      with clinical OSAS. CONCLUSION: The results of this study show that, in line with
      international publications and meta-analyses, post-tonsillectomy complications
      between H8 and H24 postoperatively, mainly bleeding, are exceptional. Respiratory
      complications usually occur in high-risk clinical settings that are not eligible
      for outpatient surgery. Outpatient tonsillectomy is therefore a safe procedure in
      children presenting all of the required medical, social and organizational
      conditions.

PMID- 21955463
TI  - Transoral robotic surgery for head and neck cancer: a series of 17 cases.
AB  - OBJECTIVES: Transoral robotic surgery (TORS) is an innovative surgical technique
      indicated for resection of selected head and neck cancers. The authors report
      their experience and discuss the indications, advantages and disadvantages of
      this technique. MATERIALS AND METHODS: Seventeen patients were operated by TORS
      in the Limoges University Hospital ENT department between March 2010 and January
      2011. RESULTS: Tumour sites were the aryepiglottic fold (n=3), piriform sinus
      (n=2), lateral pharyngeal wall (n=3), posterior pharyngeal wall (n=2), base of
      tongue (n=3), vallecula (n=1), epiglottis (n=2) and arytenoid (n=2). One patient
      had two primary sites treated by TORS. This series comprised two stage I (11.7%),
      seven stage II (41.2%), six stage III (35.4%) and two stage IVa tumours (11.7%).
      Mean TORS set-up and operating times were 20.5 and 39.7 minutes, respectively. No
      major intraoperative complication was observed. One patient was reoperated on D5
      for bleeding. Fifteen patients had clear surgical margins. Swallowing was
      restored on D2 for nine patients. The mean length of hospital stay was 10 days.
      Seven patients received adjuvant radiotherapy, seven patients were treated by
      chemoradiotherapy and three patients were submitted to simple clinical
      surveillance. CONCLUSION: TORS appears to provide new treatment options for head
      and neck cancers by extending the indications for endoscopic resection for
      selected cases of head and neck cancers. It allows effective cancer resection
      under excellent operating conditions with low morbidity and improved functional
      recovery. This new treatment modality needs to be evaluated in relation to other
      open surgery, endoscopic laser and chemoradiotherapy techniques.

PMID- 21955464
TI  - Residual cholesteatoma: prevalence and location. Follow-up strategy in adults.
AB  - OBJECTIVES: To assess prevalence and location of residual cholesteatoma following
      closed "canal wall up" tympanoplasty (CWUT). The evolution of follow-up strategy
      is discussed. PATIENTS AND METHODS: A retrospective study was run in adults
      operated on by CWUT for middle-ear cholesteatoma and who had undergone second
      look surgery and/or postoperative radiology (CT-scan, diffusion-weighted MRI).
      RESULTS: One hundred and nine patients (113 ears) underwent the procedure. Mean
      follow-up was 48 months (range, 24-96 months). Twenty-nine residual
      cholesteatomas were found (25%), including 11 located in the anterior attic
      (38%). Follow-up included 77 second look operations (70%), and 71 radiological
      examinations (62 CT-scans and nine diffusion-weighted MRIs). Second look surgery
      was without benefit for the patient (no residual, no ossiculoplasty) in one third
      of cases. CONCLUSION: Residual cholesteatoma in the anterior attic is a problem
      in CWUT. When postoperative auditory results are good, second look surgery should
      not be systematic but guided by high quality imaging.

PMID- 21955465
TI  - Development and validation of the online social support for smokers scale.
AB  - BACKGROUND: Social networks play an important role in smoking. Provision of
      social support during cessation is a cornerstone of treatment. Online social
      networks for cessation are ubiquitous and represent a promising modality for
      smokers to receive and provide the support necessary for cessation. There are no
      existing measures specific to online social support for smoking cessation.
      OBJECTIVE: The objective was to develop a measure of social support to be used in
      online smoking cessation treatment research. METHODS: Initial items for the
      Online Social Support for Smokers Scale (OS4) were based on existing theory and
      scales delineated in various taxonomies. Preliminary field analysis (N = 73) was
      conducted on 23 initial items to optimize the scale. Further development was
      conducted on a refined 15-item scale in the context of a large randomized trial
      of Internet and telephone cessation treatment with follow-ups at 3, 6, 12, and 18
      months. In all, 1326 participants were randomized to an enhanced Internet arm
      that included a large online social network; psychometric analyses employed 3
      month follow-up data from those reporting use of the enhanced Internet
      intervention at least once (n = 873). Items were subjected to a factor analysis,
      and the internal consistency reliability of the scale was examined along with
      construct and criterion validity. Other measures used in the study included
      demographics, nicotine dependence, partner support for cessation, general social
      support, social integration, stress, depression, health status, online community
      use, Internet use behaviors, intervention satisfaction, and 30-day point
      prevalence abstinence. RESULTS: The final 12-item OS4 scale demonstrated high
      internal consistency reliability (Cronbach alphas .86-.89) across demographic and
      smoking strata of interest. The OS4 also demonstrated good construct and
      criterion validity, with the directionality of the observed associations
      providing support for most a priori hypotheses. Significant Pearson correlations
      were observed between the OS4 and the Partner Interaction Questionnaire (PIQ)
      Positive subscale (rho = .24, P < .001). As hypothesized, participants with the
      highest OS4 scores were more likely to have actively participated in the enhanced
      Internet community and to have high levels of satisfaction with the enhanced
      Internet intervention. In logistic regression analyses, the OS4 was highly
      predictive of 30-day point-prevalence abstinence at 6, 12, and 18 months (all P
      values <.001). The odds of abstinence at 6 months rose by 48% for each standard
      unit increase in online social support (95% confidence interval [CI] 1.17-1.71),
      dropping only slightly to 37% at 12 and 18 months (95% CI 1.17-1.59).
      CONCLUSIONS: The OS4 is a brief, reliable, and valid instrument for measuring
      online social support for smoking cessation. Results should be replicated and
      extended, but this study suggests the OS4 can be used to advance theory,
      understand mechanisms, and potentially help to improve the tailoring of Internet
      based smoking cessation treatments. It can also inspire development of similar
      measures for other online health-related intervention research. TRIAL
      REGISTRATION: Clinicaltrials.gov #NCT00282009;
      http://clinicaltrials.gov/ct2/show/NCT00282009 (Archived by WebCite at
      http://www.webcitation.org/60XNj3xM6).

PMID- 21955466
TI  - Lack of adaptation to human tetherin in HIV-1 group O and P.
AB  - BACKGROUND: HIV-1 viruses are categorized into four distinct groups: M, N, O and
      P. Despite the same genomic organization, only the group M viruses are
      responsible for the world-wide pandemic of AIDS, suggesting better adaptation to
      human hosts. Previously, it has been reported that the group M Vpu protein is
      capable of both down-modulating CD4 and counteracting BST-2/tetherin restriction,
      while the group O Vpu cannot antagonize tetherin. This led us to investigate if
      group O, and the related group P viruses, possess functional anti-tetherin
      activities in Vpu or another viral protein, and to further map the residues
      required for group M Vpu to counteract human tetherin. RESULTS: We found a lack
      of activity against human tetherin for both the Vpu and Nef proteins from group O
      and P viruses. Furthermore, we found no evidence of anti-human tetherin activity
      in a fully infectious group O proviral clone, ruling out the possibility of an
      alternative anti-tetherin factor in this virus. Interestingly, an activity
      against primate tetherins was retained in the Nef proteins from both a group O
      and a group P virus. By making chimeras between a functional group M and non
      functional group O Vpu protein, we were able to map the first 18 amino acids of
      group M Vpu as playing an essential role in the ability of the protein to
      antagonize human tetherin. We further demonstrated the importance of residue
      alanine-18 for the group M Vpu activity. This residue lies on a diagonal face of
      conserved alanines in the TM domain of the protein, and is necessary for specific
      Vpu-tetherin interactions. CONCLUSIONS: The absence of human specific anti
      tetherin activities in HIV-1 group O and P suggests a failure of these viruses to
      adapt to human hosts, which may have limited their spread.

PMID- 21955468
TI  - Consequences of mitral valve prolapse on chordal tension: ex vivo and in vivo
      studies in large animal models.

PMID- 21955469
TI  - Recent advancements of total aortic arch replacement.
AB  - OBJECTIVE: Recent advancements in total aortic arch replacement achieved by our
      approach were presented. METHODS: From January 2002 to December 2010, 321
      consecutive patients (mean age 69.8 +/- 13.3 years) underwent total arch
      replacement through a median sternotomy at our institute. Aortic dissection was
      present in 94 (28.3%) patients and shaggy aorta in 36 (11.2%), with
      emergency/urgent surgery required in 106 (33.0%). Our current approach included
      the following: (1) meticulous selection of arterial cannulation site and type of
      arterial cannula; (2) antegrade selective cerebral perfusion; (3) maintenance of
      minimal tympanic temperature between 20  degrees C and 23  degrees C; (4) early
      rewarming just after distal anastomosis; (5) after 2004, bolus injection of 100
      mg of sivelestat sodium hydrate into the pump circuit at the initiation of
      cardiopulmonary bypass; (6) after 2006, maintaining fluid balance below 1000 mL
      during cardiopulmonary bypass. RESULTS: Overall hospital mortality was 4.4%
      (14/321) and was 1.9% (4/215) in elective cases. Permanent neurologic deficit
      occurred in 4.4% (14/321) of patients and in 2.8% (6/215) of elective cases.
      Prolonged ventilation was necessary in 53 (16.5%), with a significant reduction
      after 2006 (22.8% vs 12.6%; P = .02). Multivariate analysis demonstrated that
      risk factors for hospital mortality were octogenarian (odds ratio, 4.32; P =
      .03), brain malperfusion (odds ratio, 21.2; P = .001) and cardiopulmonary bypass
      time (odds ratio, 1.01; P = .04). Survival at 3 and 5 years after surgery was
      82.4% +/- 2.5% and 78.5% +/- 3.1%, respectively. CONCLUSIONS: Our current
      approach for total aortic arch replacement was associated with low hospital
      mortality and morbidities and with favorable long-term outcome.

PMID- 21955470
TI  - Valve sparing-root replacement with the reimplantation technique to increase the
      durability of bicuspid aortic valve repair.
AB  - OBJECTIVES: To assess root replacement and annular stabilization in bicuspid
      aortic valve repair, we compared results of reimplantation technique versus
      subcommissural annuloplasty or no annuloplasty. METHODS: Between 1995 and 2010,
      161 consecutive patients underwent bicuspid aortic valve repair. Patients
      undergoing subcommissural annuloplasty or no annuloplasty (group 1, n = 87) had
      larger root dimensions and less aortic insufficiency than did patients undergoing
      reimplantation technique (group 2, n = 74). We matched groups 1 to 1 on basis of
      those criteria. After matching (n = 106, n = 53 per group), root dimensions (41.5
      +/- 5 vs 40 +/- 4 mm; P = .2) and degree of insufficiency (2.6 +/- 1.2 vs 2.7 +/-
      1; P = .6) were similar between groups. RESULTS: Techniques of cusp repair were
      similar between groups. Group 2 had smaller preoperative left ventricular size (P
      = .02), fewer concomitant procedures (P = .02), and shorter follow-up (41 +/- 30
      vs 63 +/- 40 months; P = .003). There were no in-hospital deaths. At discharge,
      residual aortic insufficiency was similar between groups, but peak gradient
      greater than 25 mm Hg was more frequent in group 1 (13% vs 30%; P = .04). At 6
      years, overall survival was 98% +/- 3% in both groups. Freedoms from reoperation
      and aortic insufficiency greater than 2+ were significantly better in group 2
      (100% vs 90% +/- 8%; P = .03; 100% vs 77% +/- 14%; P = .002). CONCLUSIONS: In
      bicuspid aortic valve repair, root replacement with the reimplantation technique
      stabilizes the ventriculoaortic junction, improves valve mobility (low gradient),
      and is associated with improved outcomes.

PMID- 21955471
TI  - Anatomic repair for congenitally corrected transposition of the great arteries: a
      single-institution 19-year experience.
AB  - OBJECTIVE(S): Anatomic repair for congenitally corrected transposition of the
      great arteries (ccTGA) has been shown to improve patient survival. We sought to
      examine long-term outcomes in patients after anatomic repair with focus on
      results in high-risk patients, the fate of the neo-aortic valve, and occurrence
      of morphologically left ventricular dysfunction. METHODS: We conducted a
      retrospective, single-institution study of patients undergoing anatomic repair
      for ccTGA. A total of 113 patients from 1991 to March 2011 were included. Double
      switch (DS) repair was performed in 68 patients, with Rastelli-Senning (RS)-type
      repair in 45. Pulmonary artery banding for retraining was performed in 23 cases.
      Patients were followed up for survival status, morbidity, and reinterventions. A
      subgroup of 17 high-risk patients in severe heart failure, ventilated, and on
      inotropes before repair, were included. RESULTS: Median age at repair was 3.2
      years (range, 25 days to 40 years) and weight was 14.3 kg (3.2-61.4). There were
      5 (of 68; 7.4%) early deaths in the DS group and 0 (of 45) in the RS group.
      Actuarial survivals in the DS group were 87.6%, 83.9%, 83.9% at 1, 5, and 10
      years versus 91.6%, 91.6%, 77.3% in the RS group (log-rank: P = .98). Freedom
      from death, transplantation, or heart failure was significantly better in the RS
      group at 10 years (P = .03). There was no difference in reintervention at 10
      years (DS, 50.3%; RS, 49.1%; P = .44). In the DS group, the Lecompte maneuver was
      associated with late reinterventions on the pulmonary arteries. Overall survival
      in the high-risk group was 70.6%. During follow-up, 14.2% patients had poor
      function of the morphologically left ventricle, all in the DS group, but this was
      not related to preoperative status or previous banding. The majority of patients
      after DS had mild aortic incompetence, which appeared well tolerated.
      Annuloplasty of the aortic root at time of DS reduced the risk of late aortic
      valve replacement. CONCLUSIONS: There is significant morbidity after anatomic
      repair of ccTGA, which is higher in the DS than the RS group. Nevertheless, the
      majority of patients are free of heart failure at 10 years, including high-risk
      patients in severe heart failure before repair. Aortic annuloplasty may reduce
      risk of late aortic insufficiency.

PMID- 21955472
TI  - Quality of life and perceived health status in adults with congenitally corrected
      transposition of the great arteries.
AB  - OBJECTIVE: The purpose of this study is to assess perceived health status and
      quality of life in adults with congenitally corrected transposition of the great
      arteries who have not undergone anatomic repair. METHODS: Quality of life as
      measured by the satisfaction with life scale and linear analog scales and
      perceived health status as measured by the Short Form 36 Health Survey (version
      1) were evaluated in 25 adults with congenitally corrected transposition and
      compared with a control group of 25 adults with mild, hemodynamically
      insignificant defects. RESULTS: Instruments were returned by 83% of patients
      (25/30; 11 male; mean age, 44.6 +/- 16 years). Health status by the linear analog
      scale was significantly lower (P = .03) in subjects (median, 80; range, 15-100)
      than in controls (median, 85; range, 65-100). Quality of life by the satisfaction
      with life scale was also lower (P = .009) in subjects (mean, 24 +/- 8) compared
      with controls. Age was negatively correlated with the Short Form 36 Health Survey
      physical functioning (r = -0.41, P = .04), bodily pain (r = -0.5, P = .01), and
      physical component (r = -0.56, P = .004) summary scores in adults with
      congenitally corrected transposition but not in controls. CONCLUSIONS: Adults
      with congenitally corrected transposition have lower reported health status and
      satisfaction with life than a control population, with perceived health status
      declining with advancing age.

PMID- 21955474
TI  - Matrix metalloproteinase 14 and 19 expression is associated with thoracic aortic
      aneurysms.
AB  - OBJECTIVE: It is hypothesized that an altered turnover of extracellular matrix
      mediated by matrix metalloproteinases (MMPs) is present in thoracic aortic
      aneurysms. Here, we analyzed the occurrence of MMPs and MMP inhibitors in
      ascending aortic aneurysms in patients with bicuspid and tricuspid aortic valves.
      METHODS: Expression of 23 MMPs and their inhibitors was measured in aortic
      intima/media and adventitia in 109 patients (40 tricuspid, 69 bicuspid, 68 with
      aortic diameter>=4.5 cm, and 41 with <=4.0 cm) using Affymetrix Exon arrays
      (Affymetrix, Santa Clara, Calif). Gene expression was confirmed by quantitative
      real-time polymerase chain reaction. Principal components analysis was used to
      study differences in gene expression. Immunohistochemistry was used to study
      protein expression. RESULTS: We detected messenger RNA expression for gelatinases
      (MMP2 and MMP9), stromelysin 3 (MMP11), all membrane bound MMPs (MMP14, MMP15,
      MMP16, MMP17, MMP24, MMP25), MMP19, MMP21, and MMP28 in ascending aorta. No
      expression of collagenases was detected. Principal components analysis showed
      that changes in mRNA expression between dilated and nondilated aorta were mainly
      detected in patients with tricuspid aortic valves. MMP14 and MMP19 showed higher
      expression in dilated aortas and MMP19 expression correlated positively to
      maximal aortic diameter in patients with tricuspid aortic valves (Rho=0.61,
      P=.004, and Rho=0.57, P=.008, using raw and body surface area-corrected aortic
      diameter, respectively). Immunohistochemical staining demonstrated increased
      medial expression of MMP14 and MMP19 in dilated aorta. CONCLUSIONS: The present
      study identifies MMP14 and MMP19 as proteolytic enzymes potentially involved in
      aneurysm formation in the ascending aorta of patients with tricuspid aortic
      valves.

PMID- 21955475
TI  - Failure of remote ischemic preconditioning to reduce the risk of postoperative
      acute kidney injury in children undergoing operation for complex congenital heart
      disease: a randomized single-center study.
AB  - OBJECTIVE: The objective of this study was to evaluate whether remote ischemic
      preconditioning can protect kidney function in children undergoing operation for
      complex congenital heart disease. METHODS: Children (n = 113) aged 0 to 15 years
      admitted for complex congenital heart disease were randomly allocated according
      to age to remote ischemic preconditioning and control groups. After exclusion of
      8 patients, we conducted the analysis on 105 patients (remote ischemic
      preconditioning group, n = 54; control group, n = 51). Before surgery, remote
      ischemic preconditioning was performed as 4 cycles of 5 minutes of ischemia by
      inflating a cuff around a leg to 40 mm Hg above the systolic pressure. End points
      were development of acute kidney injury, initiation of dialysis, plasma
      creatinine, estimated glomerular filtration rate, plasma cystatin C, plasma and
      urinary neutrophil gelatinase-associated lipocalin, and urinary output. Secondary
      end points included postoperative blood pressure, inotropic score, and mortality,
      as well as morbidity reflected by reoperation and stays in the intensive care
      unit and hospital. RESULTS: Overall, 57 of the children (54%) had acute kidney
      injury develop, with 27 (50%) in the remote ischemic preconditioning group and 30
      (59%) in the control group (P > .2). Remote ischemic preconditioning was not
      associated with improvement in either any of the renal biomarkers or any of the
      secondary end points. CONCLUSIONS: We found no evidence that remote ischemic
      preconditioning provided protection of kidney function in children undergoing
      operation for complex congenital heart disease.

PMID- 21955476
TI  - Implantation of a Sapien XT aortic bioprosthesis with the NovaFlex catheter
      through a subclavian access.

PMID- 21955477
TI  - Hepatic pathology may develop before the Fontan operation in children with
      functional single ventricle: an autopsy study.
AB  - OBJECTIVE: Liver fibrosis has emerged as an important long-term complication of
      the Fontan operation. We aimed to describe liver histology at autopsy in patients
      who had undergone the Fontan operation and to determine whether patient variables
      are associated with the degree of fibrosis. METHODS: A review was performed of
      all patients with a history of the Fontan operation who died and underwent
      autopsy at our institution from 1980 to 2009. Autopsy liver slides were evaluated
      independently by 2 pathologists. RESULTS: Twenty-two patients were studied. The
      median interval between Fontan and death was 20 days (range, 1 day-17.5 years).
      Portal fibrosis was observed in 20 (91%) patients and sinusoidal fibrosis was
      observed in 17 (77%) patients. Using simple linear regression, time from the
      Fontan operation was significantly associated with the degree of portal fibrosis
      on Ishak (P = .03) and modified Scheuer fibrosis (P = .02) scales. Significant
      portal fibrosis was observed in 8 (57%) of the 14 patients who died 30 days or
      less after the Fontan operation. In these 14 patients, severity of portal
      fibrosis was associated with length of hospitalization after pre-Fontan cardiac
      operations (P = .03) and pre-Fontan mean right atrial pressure (P = .04).
      CONCLUSIONS: At autopsy, hepatic fibrosis was commonly observed in patients who
      had undergone the Fontan operation. Portal fibrosis has been previously
      unrecognized in this population. Significant portal fibrosis occurred in most who
      died soon after the Fontan procedure and was associated with pre-Fontan
      morbidity. Hepatic disease in the single-ventricle population is multifactorial
      and may begin before the Fontan operation.

PMID- 21955478
TI  - Preoperative left atrial dysfunction and risk of postoperative atrial
      fibrillation complicating thoracic surgery.
AB  - OBJECTIVE: Postoperative atrial fibrillation complicating general thoracic
      surgery increases morbidity and stroke risk. We aimed to determine whether
      preoperative atrial dysfunction or other echocardiographic markers are associated
      with postoperative atrial fibrillation. METHODS: In 191 patients who had
      undergone anatomic lung or esophageal resection, preoperative clinical and
      echocardiographic data were compared between patients with and without
      postoperative atrial fibrillation. Presence of postoperative atrial fibrillation
      lasting more than 5 minutes during hospitalization was detected using continuous
      telemetry or 12-lead electrocardiography. Maximal left atrial volume and indices
      of left atrial function were assessed. RESULTS: Patients with postoperative
      atrial fibrillation (33/191, 17%) were older (71 +/- 5 years vs 64 +/- 12 years,
      P < .0001), were taking beta-blockers more often, had greater left atrial volume,
      had decreased left atrial emptying fraction, and had lower E' and A' septal
      velocities compared with patients without postoperative atrial fibrillation. The
      incidence of postoperative atrial fibrillation in patients with left atrial
      volume 32 mL/m(2) or greater was 37% (11/30) and greater than in those with left
      atrial volume less than 32 mL/m(2) (14%, 22/160, P = .002). Length of hospital
      stay was significantly increased in patients with postoperative atrial
      fibrillation compared with patients without (P = .04). Older age was
      significantly associated with greater beta-blocker use and left atrial volume and
      lower left atrial emptying fraction. On multivariate analysis, lower left atrial
      emptying fraction (odds ratio, 1.03 per unit decrement; 95% confidence interval,
      1.002-1.065; P = .04) and preoperative use of beta-blockers (odds ratio, 2.82;
      95% confidence interval, 1.18-6.77; P = .02) were the only independent risk
      factors associated with postoperative atrial fibrillation. CONCLUSIONS: These
      data show that an echocardiogram before major thoracic surgery, increased use of
      preoperative beta-blockers, and decreased left atrial emptying fraction were
      associated with postoperative atrial fibrillation. Echocardiographic predictors
      of left atrial mechanical dysfunction may prove clinically useful in risk
      stratifying patients in whom postoperative atrial fibrillation is more likely to
      develop and to benefit from prevention strategies aimed at mitigating atrial
      function before surgery.

PMID- 21955479
TI  - Inefficiency as the major driver of excess costs in lung resection.
AB  - BACKGROUND: Risk-adjusted outcomes of surgical care are important for quality and
      cost assessments. Although cardiac surgery is commonly studied, risk-adjusted
      analysis of excess costs of lung resection has not been pursued. METHODS: We used
      2002 to 2005 National Inpatient Sample of the Healthcare Cost and Utilization
      Project data to evaluate adverse outcomes and costs in elective lung resections
      in hospitals with more than 20 cases during that period. Adverse outcomes were
      inpatient death or excessive risk-adjusted postoperative stay. Logistic models
      were defined to predict adverse outcomes. Linear models were designed to predict
      costs. Hospital-specific adverse outcome rates and costs were measured to define
      performance outliers. Cost-effective reference hospitals were used to define
      total excess costs. RESULTS: Among 12,182 patients at 215 hospitals undergoing
      lung resection, there were 336 inpatient deaths (2.8%) and 880 live discharges
      with prolonged risk-adjusted postoperative stay (7.2%). Predictive models for
      mortality and risk-adjusted postoperative stay had C statistics of 0.773 and
      0.643, respectively. There were 11 ineffective hospitals (5.1%) with excessive
      adverse outcomes (P < .005) and 34 inefficient hospitals (15.8%) meeting quality
      measures but with higher than predicted costs (P < .0005). Ineffective hospitals
      had costs $1020 per case lower than predicted. Inefficient hospitals had costs
      $9978 higher than predicted. CONCLUSIONS: Inefficiency is the major factor in
      excess inpatient costs associated with lung resection in this model. Although
      refinements in databases, including total physician costs and postdischarge
      adverse event costs, will alter models, excess costs of lung resection appear to
      be driven by inefficiency, not adverse outcomes.

PMID- 21955480
TI  - Sorafenib in combination with weekly topotecan in recurrent ovarian cancer, a
      phase I/II study of the Hoosier Oncology Group.
AB  - OBJECTIVE: This trial determined the efficacy and tolerability of sorafenib and
      weekly topotecan in patients with platinum-resistant ovarian cancer (OC) or
      primary peritoneal carcinomatosis (PPC). METHODS: Primary endpoints were maximum
      tolerated dose of sorafenib with weekly topotecan (phase I) and response rate
      (phase II). Secondary endpoints were progression free survival (PFS), overall
      survival (OS), toxicity, and rate of clinical benefit. Eligibility included
      recurrent platinum-resistant OC or PPC, <3 prior regimens, normal end-organ
      function. 3+3 dose escalation was used for phase I, sorafenib being tested at
      400mg and 800 mg orally daily. Topotecan dose was reduced from 4 mg/m(2) to
      3.5mg/m(2) IV weekly. The phase II regimen was sorafenib 400mg daily and
      topotecan 3.5mg/m(2) weekly on days 1, 8, 15 of a 28 days cycle. RESULTS: 16
      patients were enrolled in phase I and 14 patients in phase II. Median age was
      52.5 years (range 35-79), 27 patients had OC, and 3 PPC. Median number of cycles
      administered was 2.5 (0-15). There were 5 partial responses (PR) (16.7%), and 14
      patients (46.7%) with stable disease (SD). Four PRs were recorded during phase I
      and 1 during phase II. One of those PRs occurred in a patient with platinum
      sensitive disease. Grade 3/4 toxicities included leukopenia/neutropenia (23%),
      thrombocytopenia (17%), anemia (10%), fatigue, nausea, vomiting (7% each). One
      case of grade 3 hand-foot syndrome was recorded. CONCLUSIONS: The combination of
      sorafenib and topotecan causes significant toxicity, precluding administration of
      full doses and resulting in modest clinical efficacy in platinum resistant OC or
      PPC.

PMID- 21955481
TI  - Re: "The impact of tumor morcellation during surgery on the prognosis of patients
      with apparently early uterine leiomyosarcoma".

PMID- 21955482
TI  - Quantitative detection of RASSF1A DNA promoter methylation in tumors and serum of
      patients with serous epithelial ovarian cancer.
AB  - OBJECTIVE: Detection of cell free tumor-specific DNA methylation has been
      proposed as a potentially useful noninvasive mechanism to detect malignancies,
      including ovarian cancer, and to monitor response to treatment. However, there
      are few easily implemented quantitative approaches available for DNA methylation
      analysis. Our objectives were to develop an absolute quantitative method for
      detection of DNA methylation using RASSF1A, a known target of promoter
      methylation in ovarian cancer, and test the ability to detect RASSF1A methylation
      in tumors and serum specimens of women with ovarian cancer. METHODS: Bisulfite
      modified DNAs were subjected to real time PCR using nondiscriminatory PCR primers
      and a probe with sequence containing a single CpG site, theoretically able to
      capture the methylation status of that CpG for every allele within a given
      specimen. Input DNA was normalized to ACTB levels detected simultaneously by
      assay multiplexing. Methylation levels were established by comparison to results
      obtained from universally methylated DNA. RESULTS: The assay was able to detect
      one methylated RASSF1A allele in 100,000 unmethylated alleles. RASSF1A was
      methylated in 54 of 106 (51%) invasive serous ovarian cancers analyzed and
      methylation status was concordant in 20/20 matched preoperative serum-tumor
      pairs. Serial serum specimens taken over the course of treatment for 8 of 9
      patients showed fluctuations in RASSF1A methylation concomitant with disease
      status. CONCLUSIONS: This novel assay provides a real-time PCR-based method for
      absolute quantitation of DNA methylation. Our results support feasibility of
      monitoring RASSF1A methylation from serum samples taken over the course of
      treatment from women with ovarian cancer.

PMID- 21955483
TI  - Treatment outcomes of concurrent weekly carboplatin with radiation therapy in
      locally advanced cervical cancer patients.
AB  - OBJECTIVE: To evaluate treatment outcomes of locally advanced cervical cancer
      patients who received concurrent weekly carboplatin with radiation therapy.
      METHODS: Patients with locally advanced cervical cancer who had primary radiation
      treatment in concurrent with weekly carboplatin (100mg/m(2) or AUC 2) from 1997
      to 2008 were identified. Demographic data, chemotherapy cycles, total treatment
      time, toxicities, and treatment outcomes were recorded. RESULTS: One hundred and
      forty-eight patients with stage IIB (50.7%), IIIB (48.0%) and IVA (1.3%) cervical
      cancer patients were included in the study. Median total treatment time was 53.5
      days (range, 45-100 days). Carboplatin was given for a median number of 6 cycles
      (range, 3-6 cycles). Complete response was achieved in 142 patients (95.9%) while
      six (4.1%) had persistent diseases. Among the 142 responders, 36 experienced
      recurrences: pelvic recurrences in seven (4.7%), distant failure in 25 (16.9%),
      and both pelvic and distant in four (2.7%). The 2-year and 5-year progression
      free survival rates were 75.1% and 63.0%, respectively with the corresponding 2
      year and 5-year overall survival rates of 81.9% and 63.5%. No grade 3 or 4
      hematologic and non-hematologic toxicities were observed during treatment in any
      patients. Late grade 3-4 gastrointestinal or genitourinary toxicities were 10.1%
      and 0.7%, respectively. CONCLUSION: Concurrent weekly carboplatin with radiation
      therapy yields high response rate with modest progression-free and overall
      survivals in locally advanced cervical cancer. The regimen is feasible with
      minimal toxicities.

PMID- 21955484
TI  - Survival impact of capsule rupture in stage I clear cell carcinoma of the ovary
      in comparison with other histological types.
AB  - OBJECTIVE: We analyzed a large number of stage I clear cell carcinoma of the
      ovary (CCC) patients to estimate the survival impact of the capsule status in
      stage I CCC patients, particularly in comparison with non-CCC patients. METHODS:
      Clinicopathologic data on 564 patients with stage I epithelial ovarian cancer
      (EOC) collected under the central pathological review system were subjected to
      uni- and multivariable analyses to evaluate the disease-free survival (DFS) and
      overall survival (OS). RESULTS: There was no significant difference in both the
      OS and DFS of CCC patients between IA and IC(ir) (intraoperative capsule rupture)
      {IA vs. IC(ir); OS: P=0.1402, DFS: P=0.2701}. In contrast, CCC patients at IC(non
      ir) {IC excluding for IC(ir), such as preoperative capsule rupture, positive
      ascites/washing, and surface involvement} showed a poorer OS and DFS than those
      at IC(ir), or those at the corresponding stage in non-CCC. In multivariable
      analysis, the capsule status was an independent prognostic factor of a poor OS
      and DFS {OS: HR, 2.832; 95% CI 1.156-6.938; P=0.023; DFS: HR, 4.327; 95% CI,
      1.937-9.667; P=0.0004)} {In contrast, non-CCC: N.S. (OS/DFS)}. Furthermore, in
      CCC patients, intraperitoneal recurrences were more frequently observed in IC(non
      ir) CCC than IA or IC(ir) CCC (P=0.0083) {In contrast, non-CCC: N.S.}.
      CONCLUSION: This study suggests that CCC patients other than those with
      intraoperative capsule rupture show a considerable risk for mortality despite
      adjuvant chemotherapy.

PMID- 21955485
TI  - Refining immunotherapy for NMDAR encephalitis.

PMID- 21955486
TI  - Extraterritoriality for cross-border reproductive care: should states act against
      citizens travelling abroad for illegal infertility treatment?
AB  - Since the development of assisted reproduction technologies, there has been
      discussion on which people should have access to these technologies and which
      treatments and techniques are morally acceptable. However, national legislation
      can no longer determine what citizens do. Some countries react to their citizens
      going abroad to evade restrictions by implementing even more restrictive laws.
      Turkey has recently become the first state to ban reproductive travel in pursuit
      of donor gametes. Several states in Australia have enacted or are considering
      laws that prohibit international commercial surrogacy. This article investigates
      the consistency and morality of several state reactions to cross-border
      reproductive care (CBRC), including extraterritorial regulation. The only
      widespread existing extraterritorial regulation of private life concerns female
      genital cutting (FGC), sex with children and (largely in the past) abortion. This
      discussion develops an analogy with these cross-border crimes to evaluate the
      morality of similar legislation in cases of CBRC. The dissimilarity in these
      analogies shows that extraterritoriality is a radical position that is generally
      inappropriate in the case of CBRC. Subsequently, several potential state
      reactions to CBRC for law evasion are considered. It is concluded that
      legislation of CBRC should be modest, tolerant and nuanced.

PMID- 21955487
TI  - Implementing a good practice guide for CBRC: perspectives from the ESHRE Cross
      Border Reproductive Care Taskforce.
AB  - This article sets out views about cross-border reproductive care (CBRC) from the
      point of view of a professional clinicians' group. After publishing the first
      international European dataset measuring the phenomenon of CBRC in six European
      countries in June 2010, the European Society for Human Reproduction and
      Embryology (ESHRE) Taskforce on CBRC set out to write a good practice guide,
      which aims at advising clinicians and professionals dealing with patients
      interested in seeking fertility treatment outside their country of residence. The
      background, outline and possible means of implementation of this guide are
      discussed here. The aims of the guide are to ensure quality of care and safety
      for all concerned, from patients to their future offspring, via gamete donors and
      surrogates if involved. Patient centredness is also an important aspect, as well
      as fair treatment of all parties, based on appropriate and intelligible
      information.

PMID- 21955488
TI  - Abandoned by the State, betrayed by the Church: Italian experiences of cross
      border reproductive care.
AB  - This paper investigates the case of Italians travelling abroad for fertility
      treatments as a reaction to the restrictive Italian law regulating medically
      assisted procreation. The acknowledgement of legal limitations provokes special
      feelings of abandonment while the decision to leave the country represents
      intentions that oppose institutional positions and results in an embodied dissent
      against them. The choice of destination considers legal, medical, economic,
      logistic and cultural matters and pertains to the re-elaboration of one's own way
      of understanding reproduction and interpreting restrictive rules on the matter.
      This paper first presents the Italian law concerning assisted reproduction and
      the political, moral and cultural context in which this law has been approved,
      contested and partially modified. Then, the experiences of Italians undertaking
      cross-border reproductive care (CBRC) are analysed, focusing on feelings that
      people develop in the face of restrictive legislation and on the meaning that
      CBRC acquires in their reproductive stories. Finally, the criteria that lead
      people to take specific decisions concerning destinations are explored in order
      to show which kind of expectations and needs they have with regard to CBRC and
      which elements they deem important to consider their experience fulfilling and
      successful.

PMID- 21955489
TI  - Brokers, consumers and the internet: how North American consumers navigate their
      infertility journeys.
AB  - North Americans who suffer infertility often reach an end to treatment options at
      home, whether it is due to a lack of egg donors in Canada or the high cost of
      treatment in the USA. Patients navigate their way onto the internet, seeking
      support and other options. As women and couples 'do the research' online, they
      conduct endless Google searches, come across IVF brokers, join support groups,
      read blogs and meet others on the road of infertility. This paper considers the
      journeys that North American patients make to clinics in Moravia, Czech Republic.
      Along these travels, patients engage with support groups, other patients, IVF
      brokers and clinic co-ordinators. Since the distance travelled between North
      America and Europe is extensive, reproductive travels may be arranged by clinical
      staff, travel brokers and patients. Acting as consumers, North Americans make
      different 'choices' along their journeys - the use of a broker, if and when they
      should join online communities, which clinic to visit and where to stay. This
      study focuses on the question of how patient choices often determine the success
      of brokers and clinics, thus influencing the structure of cross-border
      reproductive care in the Czech Republic.

PMID- 21955490
TI  - Diasporic dreaming: return reproductive tourism to the Middle East.
AB  - This article attempts to capture the dynamics of return reproductive tourism to
      the Middle East, based on ethnographic research undertaken at four different
      Middle Eastern locales (Egypt, Lebanon, United Arab Emirates and Arab America).
      Across the Middle Eastern diaspora, which is now vast, due to the disruptions of
      war and political violence, infertile couples often dream of making a test-tube
      baby 'back home' for a variety of cultural, moral and psychological reasons.
      These reasons - including medical expatriotism, the language of medicine, co
      religion and moral trustworthiness, donor phenotype, the comforts of home and
      discrimination - are rarely highlighted in the scholarly literature on cross
      border reproductive care. Thus, further empirical investigation is needed in
      order to assess additional reasons for reproductive travel beyond Euro-America.
      Of particular concern are the needs of 'stranded' refugee populations, who are
      constrained from seeking assisted reproduction technology 'back home', but who
      may face economic constraints and cultural discrimination in host communities.

PMID- 21955491
TI  - General strategy to analyse melanoma in mice.

PMID- 21955493
TI  - Methods to identify, study and understand end-user participation in HIT
      development.
AB  - BACKGROUND: Experience has shown that for new health-information-technology (HIT)
      to be suc-cessful clinicians must obtain positive clinical benefits as a result
      of its implementation and joint-ownership of the decisions made during the
      development process. A prerequisite for achieving both success criteria is real
      end-user-participation. Experience has also shown that further research into
      developing improved methods to collect more detailed information on social groups
      participating in HIT development is needed in order to support, facilitate and
      improve real end-user participation. METHODS: A case study of an EHR planning
      process in a Danish county from October 2003 until April 2006 was conducted using
      process-analysis. Three social groups (physicians, IT-professionals and
      administrators) were identified and studied in the local, present perspective. In
      order to understand the interactions between the three groups, the national,
      historic perspective was included through a literature-study. Data were collected
      through observations, interviews, insight gathered from documents and relevant
      literature. RESULTS: In the local, present perspective, the administrator's
      strategy for the EHR planning process meant that there was no clinical workload
      reduction. This was seen as one of the main barriers to the physicians to
      achieving real influence. In the national, historic perspective, physicians and
      administrators have had/have different perceptions of the purpose of the patient
      record and they have both struggled to influence this definition. To date, the
      administrators have won the battle. This explains the conditions made available
      for the physicians' participation in this case, which led to their role being
      reduced to that of clinical consultants--rather than real participants.
      CONCLUSION: In HIT-development the interests of and the balance of power between
      the different social groups involved are decisive in determining whether or not
      the end-users become real participants in the development process. Real end-user
      participation is essential for the successful outcome of the process. By
      combining and developing existing theories and methods, this paper presents an
      improved method to collect more detailed information on social groups
      participating in HIT-development and their interaction during the development.
      This allows HIT management to explore new avenues during the HIT development
      process in order to support, facilitate and improve real end-user participation.

PMID- 21955494
TI  - Highly accurate and high-resolution function prediction of RNA binding proteins
      by fold recognition and binding affinity prediction.
AB  - A full understanding of the mechanism of post- transcriptional regulation
      requires more than simple two- state prediction (binding or not binding) for RNA
      binding proteins. Here we report a sequence-based technique dedicated for
      predicting complex structures of protein and RNA by combining fold recognition
      with binding affinity prediction. The method not only provides a highly accurate
      complex structure prediction (77% of residues are within 4 degrees A RMSD from
      native in average for the independent test set) but also achieves the best
      performing two-state binding or non-binding prediction with an accuracy of 98%,
      precision of 84%, and Mathews correlation coefficient (MCC) of 0.62. Moreover, it
      predicts binding residues with an accuracy of 84%, precision of 66% and MCC value
      of 0.51. In addition, it has a success rate of 77% in predicting RNA binding
      types (mRNA, tRNA or rRNA). We further demonstrate that it makes more than 10%
      improvement either in precision or sensitivity than PSI- BLAST, HHPRED and our
      previously developed structure- based technique. This method expects to be useful
      for highly accurate genome-scale, high-resolution prediction of RNA-binding
      proteins and their complex structures. A web server (SPOT) is freely available
      for academic users at http://sparks.informatics.iupui.edu.

PMID- 21955495
TI  - Construction of microRNA- and microRNA*-mediated regulatory networks in plants.
AB  - The critical biological roles of microRNAs (miRNAs) have been well recognized.
      However, knowledge on the regulatory activities of miRNA*s is limited. Although
      several studies pointed to the capacity of this small RNA species to repress
      target genes in animals, few related analyses were performed in plants. Here, we
      set out to uncover the repressive effects of miRNA*s on their targets in both
      Arabidopsis and rice. Systemic identification of miRNA*s was performed through
      secondary structure-based predictions and expression level-based verification.
      The targets of the miRNA*s were predicted and further filtered based on degradome
      sequencing data, resulting in comprehensive miRNA*--target lists with high
      reliability. Besides, comprehensive miRNA--target lists were also obtained. The
      phenomenon that one transcript was targeted by two or more miRNA(*)s was
      observed, which was defined as co-regulation. Finally, comprehensive miRNA- and
      miRNA*-mediated regulatory networks were constructed. Further investigation of
      some specific subnetworks implied the utility of these networks for biologists.
      This study could broaden the current understanding of miRNA gene-mediated
      regulation in plants.

PMID- 21955496
TI  - Multiple RNA binding domains of Bruno confer recognition of diverse binding sites
      for translational repression.
AB  - Bruno protein binds to multiple sites - BREs - in the oskar mRNA 3' UTR, thereby
      controlling oskar mRNA translation. Bruno also binds and regulates other mRNAs,
      although the binding sites have not yet been defined. Bruno has three RRM type
      RNA binding motifs, two near the amino terminus and an extended RRM at the C
      terminus. Two domains of Bruno, the first two RRMs (RRM1+2), and the extended RRM
      (RRM3+) - can each bind with specificity to the oskar mRNA regulatory regions;
      these and Bruno were used for in vitro selections. Anti-RRM3+ aptamers include
      long, highly constrained motifs, including one corresponding to the previously
      identified BRE. Anti-RRM1+2 aptamers lack constrained motifs, but are biased
      towards classes of short and variable sequences. Bruno itself selects for several
      motifs, including some of those bound by RRM3+. We propose that the different RNA
      binding domains allow for combinatorial binding, with extended Bruno binding
      sites assembled from sequences bound by the individual domains. Examples of such
      sites were identified in known targets of Bruno, and shown to confer Bruno
      dependent translational repression in vivo. Other proteins with multiple RRMs may
      employ combinatorial binding to achieve high levels of specificity and affinity.

PMID- 21955497
TI  - Role of pri-miRNA tertiary structure in miR-17~92 miRNA biogenesis.
AB  - MicroRNAs (miRNAs) regulate gene expression in a variety of biological pathways
      such as development and tumourigenesis. miRNAs are initially expressed as long
      primary transcripts (pri-miRNAs) that undergo sequential processing by Drosha and
      then Dicer to yield mature miRNAs. miR-17~92 is a miRNA cluster that encodes 6
      miRNAs and while it is essential for development it also has reported oncogenic
      activity. To date, the role of RNA structure in miRNA biogenesis has only been
      considered in terms of the secondary structural elements required for processing
      of pri-miRNAs by Drosha. Here we report that the miR-17~92 cluster has a compact
      globular tertiary structure where miRNAs internalized within the core of the
      folded structure are processed less efficiently than miRNAs on the surface of the
      structure. Increased miR-92 expression resulting from disruption of the compact
      miR-17~92 structure results in increased repression of integrin alpha5 mRNA, a
      known target of miR-92a. In summary, we describe the first example of pri-miRNA
      structure modulating differential expression of constituent miRNAs.

PMID- 21955499
TI  - The role of plasma N-terminal pro-B-type natriuretic peptide in predicting the
      severity of transient tachypnea of the newborn.
AB  - BACKGROUND/AIM: Transient tachypnea of the newborn (TTN) is a consequence of
      inadequate neonatal lung fluid clearance. Natriuretic peptides play an important
      role in the regulation of extracellular fluid volume. The aim of the study was to
      investigate the relation between plasma N-terminal pro-B-type natriuretic peptide
      (NT-proBNP) levels and TTN, and to find out its role in predicting disease
      severity. METHODS: A prospective controlled study involving 67 infants with TTN
      and 33 controls >=34 weeks gestational age was conducted. Study and control
      groups were compared for plasma NT-proBNP levels measured on the 6th, 24th, 72nd
      and 120th hours of life. Cardiac systolic functions were evaluated by
      echocardiography. RESULTS: NT-proBNP levels were significantly higher in neonates
      with TTN compared to controls at 6th, 24th, 72nd and 120th hours (p<0.001). NT
      proBNP levels at 24th and 72nd hours were significantly higher in infants with
      prolonged tachypnea (p=0.007 and p=0.03) and in those who required respiratory
      support (p=0.006 and p<0.001). Tachypnea duration was correlated with NT-proBNP
      levels at 24h (r=0.41, p=0.001). At a cut-off value of 6575 pg/ml, NT-proBNP had
      a sensitivity of 85% and specificity of 64% to predict mechanical ventilation
      requirement. Cardiac systolic functions were normal in all TTN patients.
      CONCLUSION: Plasma NT-proBNP levels are increased in neonates with TTN.
      Measurement of plasma NT-proBNP can be useful for predicting infants who will
      have prolonged tachypnea and mechanical ventilation requirement.

PMID- 21955498
TI  - Transcriptional gene silencing of HIV-1 through promoter targeted RNA is highly
      specific.
AB  - We have previously reported induction of transcriptional gene silencing (TGS) of
      HIV-1 by short hairpin RNA (shRNA) expressed in MOLT-4 cells. The shRNA (termed
      shPromA) targets the highly conserved tandem NF-kB binding sequences of the HIV-1
      promoter. Recent articles have reported that TGS mediated by promoter-targeted
      siRNAs was exclusively the result of sequence non-specific off-target effects.
      Specifically, several mismatched siRNAs to the target promoter sequences were
      reported to also induce significant TGS, suggesting TGS was a consequence of off
      target effects. Here, following extensive investigation, we report that shPromA
      induces sequence specific transcriptional silencing in HIV-1 infection in MOLT4
      cells, while four shRNA variants, mismatched by 2-3 nucleotides, fail to suppress
      viral replication. We confirm similar levels of shRNA expression from the U6
      promoter and the presence of processed/cleaved siRNAs for each construct in
      transduced MOLT-4 cells. HIV-1 sequence specific shPromA does not suppress HIV-2,
      which has an alternate NF-kB binding sequence. As a result of the unique sequence
      targeted, shPromA does not induce down-regulation of other NF-kB driven genes,
      either at the mRNA or protein level. Furthermore, we confirmed shPromA does not
      have sequence non-specific off-target effects through unaltered expression of
      CD4, CXCR4, and CCR5, which are used for viral entry. Additionally, shPromA does
      not alter PKR, IFN levels, and three downstream mediators of IFN-a response
      genes. Our data clearly shows that shPromA achieved highly specific TGS of HIV-1,
      demonstrating that effective TGS can be induced with minimal off-target effects.

PMID- 21955501
TI  - Study of mother-infant attachment patterns and influence factors in Shanghai.
AB  - BACKGROUND: In contrast to the considerable volume of international research on
      infant attachment development, significantly less research has been conducted in
      China. AIM: The present study was designed to identify the patterns of mother
      infant attachment in Shanghai and to explore the influence factors. STUDY DESIGN
      AND SUBJECTS: The subjects included 160 healthy infant-mother dyads. Infant
      attachment and temperament were assessed with the Strange Situation Procedure and
      Carey's temperament questionnaire, respectively; the mother's personality,
      maternal sensitivity and marital satisfaction were assessed with Eysenck's
      personality questionnaire, Maternal Behavior Q-sort Manual Version 3.1 and
      Olson's marital questionnaire, respectively. A self-formulated questionnaire of
      family environment factors was completed by the infant's mother. RESULTS: Of the
      160 infants, 68.2% were rated as securely attached (B) and 31.8% as insecurely
      attached. Of those infants rated as insecurely attached, 7.5% were characterized
      as avoidant (A), 21.8% as resistant (C) and 2.5% as disorganized (D). Maternal
      sensitivity and marital satisfaction as well as the approachability dimension of
      infant temperament, were significantly different between securely attached
      infants and insecurely attached infants. From a temperament perspective,
      resistant infants showed higher-level intensity of reaction than avoidant
      infants. Moreover, multiple caregivers in the family and infant's sleeping with
      other caregivers at night were more likely to be associated with insecure mother
      infant attachment. CONCLUSION: There exist certain cultural characteristics in
      mother-infant attachment patterns in Shanghai. The influence factors are related
      with the high involvement of non-mother caregivers as well as maternal
      sensitivity, marital satisfaction and infant's temperament characteristics.

PMID- 21955500
TI  - Underinvolved relationship disorder and related factors in a sample of young
      children.
AB  - BACKGROUND AND AIMS: The interaction between the infant and the caregiver is
      stated to be very important in the development of a child. When there is
      inadequacy of interaction, several emotional and developmental problems can
      emerge. We aimed to investigate the socio-demographic and clinical features of
      children diagnosed with Underinvolved Relationship Disorder according to the DC:0
      3R classification system. STUDY DESIGN AND METHODS: Four hundred and fifty seven
      children aged between 1 and 59 months, who had been admitted to an infant mental
      health clinic were assessed using the DC:0-3R classification system and the whole
      sample was divided into two groups, the group in which Underinvolved Relationship
      Disorder between the child and the caregiver had been detected (URD), and the
      group in which this had not been detected (NURD). These two groups were compared
      with regard to socio-demographic features, reasons for referral, primary
      diagnoses, relational disorders, medical/developmental conditions, psychosocial
      stressors and the Parent-Infant Relationship Global Assessment Scale (PIRGAS)
      scores of children. RESULTS: Language delay, insufficient social interaction and
      aggression were found to be significantly more frequent reasons for referral in
      URD. Disorders of Relating and Communicating (equivalent to the Pervasive
      Developmental Disorders in DSM IV) and Deprivation/Maltreatment Disorder were
      more frequent primary diagnoses, Verbally or Physically Abusive Relationship
      Disorder was significantly more frequent relational disorder in URD. Mild and
      moderate mental retardation were significantly more frequent in URD, and social
      environment, educational/child care and health-care access challenges were found
      to be more frequent psychosocial stressors in the parents of URD. The Mean PIRGAS
      scores were significantly lower in URD connoting that the parent-infant
      relationship is poorer. CONCLUSIONS: The diagnosis of Underinvolved Relationship
      Disorder according to the DC:0-3R classification system is related to some
      developmental and psychosocial problems.

PMID- 21955502
TI  - Visual function assessment in late-preterm newborns.
AB  - AIM: To describe the development of visual functions in a population of low-risk
      late preterm infants. SUBJECTS AND METHODS: Eighty low-risk late preterm with a
      gestational age between 34.0 and 36.9 weeks were assessed at birth and at term
      equivalent age (TEA) using a structured visual assessment battery. The results
      were compared to those previously obtained in term born infants using the same
      battery. RESULTS: For 5 items (spontaneous ocular motility, ocular motility with
      target, fixation, horizontal tracking and color tracking) the results were
      similar both at birth and TEA; for the other 4 (vertical and arc tracking,
      ability to discriminate striped black/white targets and attention at distance)
      visual findings at TEA were more mature than at birth. Comparing the responses in
      late preterm at TEA and term-born infants at 48 h of life, only 2 items
      (attention at distance, ability to discriminate black/white stripes) were
      different, with more mature findings in late preterm infants. CONCLUSIONS: Our
      results show that in late preterm some aspects of visual functions have a
      progressive maturation infants between birth and TEA, confirming that the time
      between birth and term age appears to be crucial for the development of these
      abilities.

PMID- 21955503
TI  - Personality and stress appraisal in adults prenatally exposed to the Dutch
      famine.
AB  - BACKGROUND: Previous studies have shown that prenatal exposure to the Dutch
      famine is associated with an increased risk for several psychiatric disorders.
      Variation in personality characteristics and in stress appraisal may underlie
      mental disorders. AIMS: To investigate whether prenatal famine exposure is
      associated with personality characteristics and stress appraisal. STUDY DESIGN:
      Cohort study. SUBJECTS: Participants included a total of 572 men and women, born
      as term singletons in a local hospital in Amsterdam around the time of the 1944
      1945 Dutch famine. OUTCOME MEASURES: Scores on the Big Five Inventory and the
      Perceived Stress Scale (PSS). RESULTS: There were no statistically significant
      differences in the personality traits openness, conscientiousness, extraversion,
      agreeableness and neuroticism or in PSS scores between those unexposed and those
      exposed to famine during early, mid or late gestation. However, there were
      statistically significant (P=0.01) and borderline significant interactions
      (P=0.07) respectively between exposure to famine during early gestation and sex
      on conscientiousness and agreeableness. Subsequent analyses showed that men
      exposed to famine during early gestation had lower conscientiousness scores and
      women exposed during early gestation had higher agreeableness scores.
      CONCLUSIONS: We conclude that conscientiousness and agreeableness may differ
      between men and women unexposed and exposed to famine during early gestation. As
      evidence was not very robust, future research should confirm the present
      findings.

PMID- 21955504
TI  - A novel method of AquaporinZ incorporation via binary-lipid Langmuir monolayers.
AB  - In this work, a new approach of incorporating transmembrane protein AquaporinZ
      (AqpZ) into a lipid bilayer has been developed with the aid of the Langmuir
      Blodgett technique. The binary-lipid monolayer for AqpZ incorporation is composed
      of (1) gel-phase lipids resistant to detergent dissolution and (2) nickel
      chelating lipids that can attach the histidine-tagged AqpZ from the subphase.
      Upon removal of subphase detergent with BioBeads, the incorporation is achieved
      by transferring the AqpZ-associated binary-lipid monolayer onto a preformed pure
      binary-lipid monolayer using the Langmuir-Schaefer deposition method. AFM images
      show an indication of AqpZ incorporation in the bilayer. Furthermore, it is also
      shown that BioBeads can remove a significant amount of detergent in the subphase
      and lipid film integrity is restored after detergent removal. The detergent
      removal rate is correlated to BioBeads amount and subphase circulation. The new
      approach of AqpZ reconstitution revealed in this work could potentially be
      applied in biomimetic membrane formation for water purification applications.

PMID- 21955505
TI  - Synthesis and release studies of microalgal oil-containing microcapsules prepared
      by complex coacervation.
AB  - Microalgal oil was encapsulated in gelatin-gum Arabic complex coacervated
      matrices using transglutaminase (TG) as cross-linking agent. The effects of
      various cross-linking parameters including hardening time, temperature, pH and TG
      concentration on the oil release rate of the complex coacervation microcapsules
      (CCMs) were investigated, with sodium dodecyl sulfate (SDS) as release medium.
      The optimum parameters were as follows: hardening for 6h at 15 degrees C and pH
      6.0 with TG concentration of 15 U/g gelatin. The microcapsules obtained under
      optimum conditions had the lowest oil release rate. By analyzing the oil release
      curves, it was found that the oil release rate did not exactly fit the modified
      first-order kinetic model but exhibited early time and late time approximations
      for unsteady state diffusion. A greater initial release of oil was clearly
      observed whatever cross-linking parameters were, while the release profile became
      constant indicating some sustained release after the first hour.

PMID- 21955506
TI  - Experimental evidence and structural modeling of nonstoichiometric (010) surfaces
      coexisting in hydroxyapatite nano-crystals.
AB  - High-resolution transmission electron microscopy (HRTEM) and ab initio quantum
      mechanical calculations of electronic structure were combined to investigate the
      structure of the hydroxyapatite (HA) (010) surface, which plays an important role
      in HA interactions with biological media. HA was synthesized by in vitro
      precipitation at 37 degrees C. HRTEM images revealed thin elongated rod
      nanoparticles with preferential growth along the [001] direction and terminations
      parallel to the (010) plane. The focal series reconstruction (FSR) technique was
      applied to develop an atomic-scale structural model of the high-resolution
      images. The HRTEM simulations identified the coexistence of two structurally
      distinct terminations for (010) surfaces: a rather flat Ca(II)-terminated surface
      and a zig-zag structure with open OH channels. Density functional theory (DFT)
      was applied in a periodic slab plane-wave pseudopotential approach to refine
      details of atomic coordination and bond lengths of Ca(I) and Ca(II) sites in
      hydrated HA (010) surfaces, starting from the HRTEM model.

PMID- 21955507
TI  - Improving immobilization of lipase onto magnetic microspheres with moderate
      hydrophobicity/hydrophilicity.
AB  - Magnetic microspheres with carboxyl groups were prepared by copolymerization of
      vinyl acetate (VAC), acrylamide (AM), and acrylic acid (AA) in the presence of
      oleic acid-coated Fe(3)O(4) nanoparticles. Scanning electron microscope (SEM)
      photo showed that the average diameter of magnetic microspheres was about 400 nm.
      Also, FTIR spectra analysis indicated that monomers were successfully enfolded on
      the microspheres' surface. They were used as support to immobilize lipase via
      physical adsorption and covalent binding. To investigate the effect of the
      microsphere surface properties on lipase immobilization, a series of microspheres
      with different hydrophobic/hydrophilic surface characteristics were prepared by
      adjusting molar percentages of different monomers. The results showed that
      microspheres with different hydrophobicities/hydrophilicities had different
      immobilized ratios and different activity recovery. Compared with microspheres
      having hydrophilic characteristics, that with hydrophobic characteristics had a
      much higher lipase binding efficiency. However, this study further demonstrated
      that moderate hydrophobicity/hydrophilicity of microsphere surface was very
      important for elevating activity recovery. When AM (hydrophilic monomer) held
      14.3% of total amount of monomers, the activity recovery was the highest
      (reaching 87%, 418 U/g support). Possible reasons for these observations were
      discussed and a supposed mechanism was speculated.

PMID- 21955508
TI  - Electropolymerized molecular imprinting on gold nanoparticle-carbon nanotube
      modified electrode for electrochemical detection of triazophos.
AB  - An electrochemical sensor for pesticide triazophos (TAP) was prepared by
      deposition of gold nanoparticles (AuNPs) on carbon nanotubes (CNTs) modified
      glassy carbon (GC) electrode surface using a potentiostatic method, followed by
      electropolymerizing of o-hydroxyphenol at the AuNP/CNT/GC electrode surface in
      the presence of template triazophos via cyclic voltammetry. The electrochemical
      response of triazophos at the TAP-imprinted polyhydroxyphenol (PHP) modified
      AuNP/CNT/GC (PHP/AuNP/CNT/GC) electrode was investigated by cyclic voltammetry.
      The cyclic voltammetric response of triazophos at the TAP-imprinted
      PHP/AuNP/CNT/GC electrode was significantly higher than that at bare GC, CNT/GC,
      AuNP/CNT/GC, imprinted PHP/CNT/GC and non-imprinted PHP/AuNP/CNT/GC electrodes.
      The results indicated that the TAP-imprinted PHP/AuNP/CNT/GC electrode can
      effectively improve the reductive properties of triazophos and eliminate
      interferences of other pesticides. In addition, the AuNPs can strikingly amplify
      the electrochemical response of triazophos and improve the sensitivity to
      triazophos. Finally, the electrochemical sensor was successfully applied to
      determination of triazophos in vegetable samples with satisfactory results.

PMID- 21955509
TI  - Characterisation of spin coated engineered Escherichia coli biofilms using atomic
      force microscopy.
AB  - The ability of biofilms to withstand chemical and physical extremes gives them
      the potential to be developed as robust biocatalysts. Critical to this issue is
      their capacity to withstand the physical environment within a bioreactor; in
      order to assess this capability knowledge of their surface properties and
      adhesive strength is required. Novel atomic force microscopy experiments
      conducted under growth conditions (30 degrees C) were used to characterise
      Escherichia coli biofilms, which were generated by a recently developed spin
      coating method onto a poly-l-lysine coated glass substrate. High-resolution
      topographical images were obtained throughout the course of biofilm development,
      quantifying the tip-cell interaction force during the 10 day maturation process.
      Strikingly, the adhesion force between the Si AFM tip and the biofilm surface
      increased from 0.8 nN to 40 nN within 3 days. This was most likely due to the
      production of extracellular polymer substance (EPS), over the maturation period,
      which was also observed by electron microscopy. At later stages of maturation,
      multiple retraction events were also identified corresponding to biofilm surface
      features thought to be EPS components. The spin coated biofilms were shown to
      have stronger surface adhesion than an equivalent conventionally grown biofilm on
      the same glass substrate.

PMID- 21955510
TI  - Institutionalizing telemedicine applications: the challenge of legitimizing
      decision-making.
AB  - During the last decades a variety of telemedicine applications have been trialed
      worldwide. However, telemedicine is still an example of major potential benefits
      that have not been fully attained. Health care regulators are still debating why
      institutionalizing telemedicine applications on a large scale has been so
      difficult and why health care professionals are often averse or indifferent to
      telemedicine applications, thus preventing them from becoming part of everyday
      clinical routines. We believe that the lack of consolidated procedures for
      supporting decision making by health care regulators is a major weakness. We aim
      to further the current debate on how to legitimize decision making about the
      institutionalization of telemedicine applications on a large scale. We discuss
      (1) three main requirements--rationality, fairness, and efficiency--that should
      underpin decision making so that the relevant stakeholders perceive them as being
      legitimate, and (2) the domains and criteria for comparing and assessing
      telemedicine applications--benefits and sustainability. According to these
      requirements and criteria, we illustrate a possible reference process for
      legitimate decision making about which telemedicine applications to implement on
      a large scale. This process adopts the health care regulators' perspective and is
      made up of 2 subsequent stages, in which a preliminary proposal and then a full
      proposal are reviewed.

PMID- 21955511
TI  - Clinical results of a surgical technique using endobuttons for complete tendon
      tear of pectoralis major muscle: report of five cases.
AB  - BACKGROUND: We herein describe a surgical technique for the repair of complete
      tear of the pectoralis major (PM) tendon using endobuttons to strengthen initial
      fixation. METHODS: Five male patients (3 judo players, 1 martial arts player, and
      1 body builder) were treated within 2 weeks of sustaining complete tear of the PM
      tendon. Average age at surgery and follow-up period were 28.4 years (range, 23
      33) and 28.8 months (range, 24-36). A rectangular bone trough (about 1 * 4 cm)
      was created on the humerus at the insertion of the distal PM tendon. The tendon
      stump was introduced into this trough, and fixed to the reverse side of the
      humeral cortex using endobuttons and non-absorbable suture. Clinical assessment
      of re-tear was examined by MRI. Shoulder range of motion (ROM), outcome of
      treatment, and isometric power were measured at final follow-up. RESULTS: There
      were no clinical re-tears, and MRI findings also showed continuity of the PM
      tendon in all cases at final follow-up. Average ROM did not differ significantly
      between the affected and unaffected shoulders. The clinical outcomes at final
      follow-up were excellent (4/5 cases) or good (1/5). In addition, postoperative
      isometric power in horizontal flexion of the affected shoulder showed complete
      recovery when compared with the unaffected side. CONCLUSIONS: Satisfactory
      outcomes could be obtained when surgery using the endobutton technique was
      performed within 2 weeks after complete tear of the PM tendon. Therefore, our new
      technique appears promising as a useful method to treat complete tear of the PM
      tendon.

PMID- 21955512
TI  - Anti-hepatitis B surface immunoglobulin reduction in early postoperative period
      after liver transplantation in hepatitis B virus-positive patients.
AB  - AIM:   We investigated a protocol that lowered the necessary dose of anti
      hepatitis B surface immunoglobulin (HBIg) with frequent monitoring of hepatitis B
      surface antigen (HBsAg) and antibody (HBsAb) levels in the early post-transplant
      period. METHODS:   Fifteen hepatitis B virus (HBV)-positive patients were
      studied. We administered a nucleoside analog from the preoperative period, high
      dose HBIg was used intraoperatively (200 IU/kg in the patients who weighed less
      than 50 kg, and 10 000 IU in those who weighed more than or equal to 50 kg) and
      was continued every day (5000-10 000 IU/day). Thereafter, HBIg was administered
      to keep the target trough titers. We evaluated the effectiveness and safety of
      this protocol for preventing HBV reactivation. RESULTS:   The average use of HBIg
      during the first three postoperative months (POM) was 27.9 +/- 9.6 Kilo
      International Units. The average cost was $US11 800 in the first three
      postoperative months, compared with other previously reported protocols (about
      $20 000-40 000). HBV reactivation was detected in only one patient (6.7%) during
      the median follow up of 64 months (range: 12-86 months). CONCLUSIONS:   The
      present protocol for HBIg administration, which used frequent monitoring of HBsAg
      and HBsAb levels to determine the minimum required dose, was both safe and
      effective, and contributed to overall cost saving after liver transplantation.

PMID- 21955513
TI  - Ankyrin repeat and SOCS box containing protein 4 (Asb-4) colocalizes with insulin
      receptor substrate 4 (IRS4) in the hypothalamic neurons and mediates IRS4
      degradation.
AB  - BACKGROUND: The arcuate nucleus of the hypothalamus regulates food intake.
      Ankyrin repeat and SOCS box containing protein 4 (Asb-4) is expressed in
      neuropeptide Y and proopiomelanocortin (POMC) neurons in the arcuate nucleus,
      target neurons in the regulation of food intake and metabolism by insulin and
      leptin. However, the target protein(s) of Asb-4 in these neurons remains unknown.
      Insulin receptor substrate 4 (IRS4) is an adaptor molecule involved in the signal
      transduction by both insulin and leptin. In the present study we examined the
      colocalization and interaction of Asb-4 with IRS4 and the involvement of Asb-4 in
      insulin signaling. RESULTS: In situ hybridization showed that the expression
      pattern of Asb-4 was consistent with that of IRS4 in the rat brain. Double in
      situ hybridization showed that IRS4 colocalized with Asb-4, and both Asb-4 and
      IRS4 mRNA were expressed in proopiomelanocortin (POMC) and neuropeptide Y (NPY)
      neurons within the arcuate nucleus of the hypothalamus. In HEK293 cells co
      transfected with Myc-tagged Asb-4 and Flag-tagged IRS4, Asb-4 co
      immunoprecipitated with IRS4; In these cells endogenous IRS4 also co
      immunoprecipitated with transfected Myc-Asb-4; Furthermore, Asb-4 co
      immunoprecipitated with IRS4 in rat hypothalamic extracts. In HEK293 cells over
      expression of Asb-4 decreased IRS4 protein levels and deletion of the SOCS box
      abolished this effect. Asb-4 increased the ubiquitination of IRS4; Deletion of
      SOCS box abolished this effect. Expression of Asb-4 decreased both basal and
      insulin-stimulated phosphorylation of AKT at Thr308. CONCLUSIONS: These data
      demonstrated that Asb-4 co-localizes and interacts with IRS4 in hypothalamic
      neurons. The interaction of Asb-4 with IRS4 in cell lines mediates the
      degradation of IRS4 and decreases insulin signaling.

PMID- 21955514
TI  - Five-year results of fissurectomy for chronic anal fissure: low recurrence rate
      and minimal effect on continence.
AB  - AIM: The aim of the study was to determine the long-term outcome, recurrence rate
      and faecal incontinence score after fissurectomy for chronic anal fissure (CAF)
      not responding to conservative treatment. METHOD: Fifty-three consecutive
      patients (29 women) who underwent fissurectomy for a medically resistant CAF
      between 1998 and 2005 were included in the study. At a minimum follow-up of 5
      years a standardized questionnaire was sent to all patients, assessing
      recurrence, satisfaction with the operation (on a scale of 0-10) and faecal
      continence (Vaizey score, 0-24). The patients were compared with a control group
      of 50 healthy volunteers, matched for sex and age, who had never undergone anal
      surgery. RESULTS: Forty-three (81%) patients (25 women) returned the
      questionnaire. The mean age was 40 (SD 12.1) years and median follow up was 8.2
      (5.5-12.2) years. Five patients had a recurrent CAF (11.6%). Ninety per cent of
      patients would have consented to the operation again if necessary. The mean
      Vaizey score at follow-up was 2.5 (SD +/- 4.2). The mean Vaizey score of the four
      patients who had had a previous lateral sphincterotomy was 3.8 and for the eight
      patients who had reported a continence disturbance before fissurectomy it was
      8.3. The mean Vaizey score of the 31 patients who were continent before
      fissurectomy was 0.8 compared with 0.4 in the control group (P = 0.9).
      CONCLUSION: At 5 years or more fissurectomy for medically resistant CAF is
      effective with a low recurrence rate and minimal influence on continence.

PMID- 21955515
TI  - Left-sided grafts for living-donor liver transplantation and split grafts for
      deceased-donor liver transplantation: their impact on long-term survival.
AB  - BACKGROUND: A small-for-size graft is important in living-donor liver
      transplantation (LDLT) and deceased-donor liver transplantation (DDLT). SUBJECTS
      AND METHODS: First, we confirmed the effect of initial graft volume on survival
      using a rat model of liver transplantation (LT). We then evaluated the actual
      long-term survival based on graft type in 1421 LTs (including 1364 LDLTs) at
      Kyoto University and 2000 DDLTs at the Mayo Clinic, to evaluate donor safety in
      LDLT and the possibility of shifting to split orthotopic liver transplantation
      (SOLT) in DDLT. RESULTS: In the rat model, SOLTs with 40%- and 20%-grafts had a
      poor survival. A total of 697 pediatric LTs showed good long-term outcomes
      (survival rate was 0.764 at 21.2 years). The survival rate of 724 adult LTs was
      0.664 at 17.8 years. The survival rates of auxiliary partial orthotopic liver
      transplantation with a left-sided graft (0.421 at 15.0 years) and SOLT with a
      left-sided graft (0.000 at 0.8 years) need to be improved. Although the survival
      rate of 1965 adult DDLTs with a whole-liver graft in the Mayo Clinic was 0.727 at
      12.8 years, that of adult SOLT was 0.595 at 11.0 years. CONCLUSION: From the
      viewpoint of greater donor safety and expanded donor candidates in LDLT, the
      choice of a left-sided graft still remains controversial. A shift to SOLT to
      achieve excellent results should be established to resolve a donor shortage in
      DDLT.

PMID- 21955516
TI  - Endoscopic intervention for symptomatic choledocholithiasis in pregnancy.

PMID- 21955517
TI  - Immune reconstitution syndrome presenting as probable AIDS-related lymphoma: a
      case report.
AB  - We report an unusual case of HIV-related immune reconstitution inflammatory
      syndrome, presenting as suspected AIDS-related lymphoma. Symptoms, initial
      investigations including fine-needle biopsy and 18F-FDG PET/CT scan were highly
      compatible with high grade AIDS-related lymphoma, however subsequently IRIS was
      diagnosed. We discuss pitfalls in the interpretation of diagnostic results in ARL
      versus IRIS.

PMID- 21955518
TI  - A comparison of bond strengths measured using cantilever bending and micro
      tensile methods.
AB  - OBJECTIVES: The purpose of this study was to evaluate the cantilever-bending test
      as a bond-strength measurement method for enamel/composite adhesion. MATERIALS
      AND METHODS: The buccal surface of bovine incisors were flattened and
      subsequently placed with composite Z250 (3M ESPE) incrementally after either self
      etching adhesive (SE) or etch-and-rinse adhesive (SB) was applied. Then, they
      were cut with a low-speed cutter to obtain stick-shape samples. The samples were
      divided into four groups (n=30 each) according to the adhesive and test method:
      SET, SE-B, SB-T and SB-B, where T denotes the microtensile test and B denotes the
      cantilever-bending test. The failure mode of each sample was examined under the
      microscope. Those samples with the fracture surface lying entirely or partially
      in the adhesive layer were considered to have provided successful measurements.
      The results from the two test methods were compared. RESULTS AND DISCUSSION: The
      cantilever-bending method produced a comparable success rate of bond strength
      measurement to that of the microtensile method. The bond strengths of SE and SB
      from the cantilever-bending test were 58% and 40% higher, respectively, than
      those measured with the microtensile method. The adhesive SE exhibited almost the
      same bond strength as SB, irrespective of the test method. CONCLUSIONS:
      Cantilever bending can be used as an alternative method for bond strength
      measurement. The ratio of bending to tensile strength is around 1.5.

PMID- 21955519
TI  - Social stress promotes and gamma-aminobutyric acid inhibits tumor growth in mouse
      models of non-small cell lung cancer.
AB  - Psychologic distress is associated with increased lung cancer incidence and
      mortality. We have shown that non-small cell lung cancer (NSCLC) cells in vitro
      are stimulated by the cyclic AMP (cAMP)-dependent activation of cAMP-responsive
      element binding protein (CREB) and extracellular signal-regulated kinase (ERK)
      downstream of beta-adrenergic receptors and that this pathway is inhibited by the
      neurotransmitter gamma-aminobutyric acid (GABA). Because the stress
      neurotransmitters noradrenalin and adrenalin are beta-adrenergic agonists, the
      current study has tested the hypothesis that social stress stimulates NSCLC
      growth in vivo and that GABA inhibits this effect. Social stress was induced in
      mice carrying xenografts from two NSCLC cell lines in the presence and absence of
      treatment with GABA. Xenograft sizes were measured after 30 days. Noradrenalin,
      adrenalin, cortisol, GABA, and cAMP were measured in blood and tumor tissues by
      immunoassays. Expression of nicotinic receptors in the xenografts was assessed by
      real-time PCR and Western blotting. Protein expression of phospho (p)-CREB, CREB,
      phospho (p)-ERK, ERK, and glutamate decarboxylase (GAD) 65 and 67 were determined
      by Western blotting. Xenograft sizes in stress-exposed mice were significantly
      increased. Nicotinic acetylcholine receptor (nAChR) subunits alpha3, alpha4,
      alpha5, and alpha7 in xenograft tissues showed posttranscriptional induction.
      Noradrenalin, adrenalin, and cortisol were elevated in serum and xenograft tissue
      whereas GABA was suppressed. Levels of cAMP, p-CREB, and p-ERK were increased
      whereas GAD65 and GAD67 were suppressed in tumor tissue. Treatment with GABA
      reversed the effects of stress. Our findings suggest that social stress
      stimulates NSCLC by increasing nAChR-mediated stress neurotransmitter signaling
      and that GABA is a promising novel agent for NSCLC intervention.

PMID- 21955522
TI  - Prevalence of diabetic retinopathy in Norway: report from a screening study.
AB  - PURPOSE: The purpose of the present study was to investigate the prevalence of
      diabetic retinopathy (DR) in Norway and adherence to the Norwegian Guidelines for
      screening for diabetic eye disease. METHODS: Two hundred and ninety-nine people
      with diabetes were randomly recruited from the patient lists of randomly selected
      general practitioners from three different regions in Norway. Retinopathy was
      evaluated from retinal photographs after dilation of the pupils using a red-free
      digital camera and visual acuity was measured using the Snellen chart. The
      patients were interviewed about their ophthalmological and general diabetes
      control, duration and type of diabetes and medical treatment. RESULTS: The
      prevalence of any DR was 28%, 66% for type 1 and 24% for type 2 diabetes. The
      prevalence of proliferative retinopathy was 38% in type 1 and 1.5% in type 2
      diabetes. Two patients (one type 1 and one insulin-treated type 2) were visually
      impaired (visual acuity 0.3 or worse in the better eye) because of proliferative
      DR. Twenty-six per cent of the patients had never been to an eye examination, and
      only 69% attended routine eye examinations. Patients who did not attend regular
      eye screenings were mostly people with type 2 diabetes. CONCLUSION: The
      prevalence of DR was higher than previously reported in Norway. Screening for DR
      did not follow guidelines in a considerable proportion of the patients with type
      2 diabetes. There is place for improvement in the implementation of guidelines
      for screening for DR for people with type 2 diabetes in Norway.

PMID- 21955521
TI  - Opportunities for the primary prevention of colorectal cancer in the United
      States.
AB  - Several studies indicate that screening in combination with lifestyle
      modification may produce a greater reduction in colorectal cancer rates than
      screening alone. To identify national opportunities for the primary prevention of
      colorectal cancer, we assessed the prevalence of modifiable lifestyle risk
      factors in the United States. We used nationally representative, cross-sectional
      data from 5 NHANES cycles (1999-2000, n = 2,753; 2001-2002, n = 3,169; 2003-2004,
      n = 2,872; 2005-2006, n = 2,993; 2007-2008, n = 3,438). We evaluated the 5
      colorectal cancer risk factors deemed "convincing" by the World Cancer Research
      Fund (obesity, physical inactivity, intake of red meat, processed meat, alcohol),
      and cigarette smoking, a "suggestive" risk factor in the Surgeon General's
      report. We estimated the prevalence of each risk factor separately and jointly,
      and report it overall, and by sex, race/ethnicity, age, and year. In 2007 to
      2008, 81% percent of U.S. adults, aged 20 to 69 years, had at least one
      modifiable risk factor for colorectal cancer. More than 15% of those younger than
      50 years had 3 or more risk factors. There was no change in the prevalence of
      risk factors between 1999 and 2008. The most common risk factors were risk
      factors for other chronic diseases. Our findings provide additional support for
      the prioritization of preventive services in health care reform. Increasing
      awareness, especially among young adults, that lifestyle factors influence
      colorectal cancer risk, and other chronic diseases, may encourage lifestyle
      changes and adherence to screening guidelines. Complementary approaches of
      screening and lifestyle modification will likely provide the greatest reduction
      of colorectal cancer.

PMID- 21955520
TI  - Stem cell antigen-1 deficiency enhances the chemopreventive effect of peroxisome
      proliferator-activated receptorgamma activation.
AB  - Stem cell antigen-1 (Sca-1, Ly6A) is a glycerophosphatidylinositol (GPI)-anchored
      protein that was identified as a murine marker of bone marrow stem cells.
      Although Sca-1 is widely used to enrich for stem and progenitor cells in various
      tissues, little is known about its function and associated signaling pathways in
      normal and malignant cells. Here, we report that the absence of Sca-1 in the
      mammary gland resulted in higher levels of PPARgamma and PTEN, and a reduction of
      pSer84PPARgamma, pERK1/2, and PPARdelta. This phenotype correlated with markedly
      increased sensitivity of Sca-1 null mice to PPARgamma agonist GW7845 and
      insensitivity to PPARdelta agonist GW501516. Reduction of Sca-1 expression in
      mammary tumor cells by RNA interference resulted in a phenotype similar to the
      Sca-1 deficient mammary gland, as evidenced by increased PPARgamma expression and
      transcriptional activity, resulting in part from a lesser susceptibility to
      proteasomal degradation. These data implicate Sca-1 as a negative regulator of
      the tumor suppressor effects of PPARgamma.

PMID- 21955523
TI  - Health services performance for TB treatment in Brazil: a cross-sectional study.
AB  - ABSTRACT:  BACKGROUND: Researches to evaluate Primary Health Care performance in
      TB control in Brazil show that different cities aggregate local specificities in
      the dynamics of coping with the disease. This study aims to evaluate health
      services' performance in TB treatment in cities across different Brazilian
      regions. METHODS: This cross-sectional study was conducted in five cities that
      are considered priorities for TB control in Brazil: Itaborai (ITA), Ribeirao
      Preto (RP) and Sao Jose do Rio Preto (SJRP) in the Southeast; Campina Grande (CG)
      and Feira de Santana (FS) in the Northeast. Data were collected through
      interviews with 514 TB patients under treatment in 2007, using the Primary Care
      Assessment Tool adapted for TB care in Brazil. Indicators were constructed based
      on the mean response scores (Likert scale) and compared among the study sites.
      RESULTS: "Access to treatment" was evaluated as satisfactory in the Southeast and
      regular in the Northeast, which displayed poor results on 'home visits' and
      'distance between treatment site and patient's house'. "Bond" was assessed as
      satisfactory in all cities, with a slightly better performance in RP and SJRP.
      "Range of services" was rated as regular, with better performance of southeastern
      cities. 'Health education', 'DOT' and 'food vouchers' were less offered in the
      Northeast. "Coordination" was evaluated as satisfactory in all cities. "Family
      focus" was evaluated as satisfactory in RP and SJRP, and regular in the others.
      'Professional asking patient's family about other health problems' was evaluated
      as unsatisfactory, except in RP. CONCLUSIONS: Two types of obstacles are faced
      for health service performance in TB treatment in the cities under analysis,
      mainly in the Northeast. The first is structural and derives from difficulties to
      access health services and actions. The second is organizational and derives from
      the way health technologies and services are distributed and integrated.
      Incentives to improve care organization and management practices, aimed at the
      integration of primary, secondary and tertiary services, can contribute towards a
      better performance of health services in TB treatment.

PMID- 21955524
TI  - Radiation damping on cryoprobes.
AB  - Radiation damping on 600 and 800 MHz cryoprobes was investigated. The phase angle
      beta between a vector 90 degrees  phase shifted to the precessing magnetization
      and the rf field induced in the coil was found to depend markedly on whether an
      FID was being acquired or not. The magnitude of the radiation damping field was
      sufficiently strong to restore 95% of the equilibrium water magnetization of a
      90% H2O sample in a 5 mm sample tube within about 5 ms following a 165 degrees 
      pulse. This can be exploited in water flip-back versions of NOESY and TOCSY
      experiments of proteins, but care must be taken to limit the effect of the
      radiation damping field from the water on the Ha protons. Long water-selective
      pulses can be applied only following corrections. We developed a program for
      correcting pulse shapes if beta is non-zero. The WATERGATE scheme is shown to be
      insensitive to imperfections introduced by radiation damping.

PMID- 21955525
TI  - Laryngomalacia: the role of gender and ethnicity.
AB  - INTRODUCTION: The vast majority of infants in published studies regarding
      laryngomalacia are Caucasian. These studies suggest affected infants are likely
      to be male, of term pregnancies, and not of low birth weight. Our study seeks to
      identify possible associations among different genders and ethnicities with
      laryngomalacia as well as differences between our diverse population and
      published Caucasian-predominant studies. METHODS: Data was collected by chart
      review for seventy-eight children diagnosed with laryngomalacia before the age of
      5, prospectively entered into a database at our academic, tertiary-care hospital
      from 1/16/2008 to 10/15/2010. Data was compared to expected values from the 2009
      census data for the Bronx as well as published data in the literature for
      multiple factors, including gender, ethnicity, low birth weight, and prematurity.
      RESULTS: There were 45 male and 33 female infants in our study. Twenty-five
      children were African-American, 17 Hispanic, 12 multi-racial, and 4 Caucasian.
      Eighteen infants were premature, and 21 were of low birth weight. Twenty-eight
      percent of our infants had neurologic comorbidity at diagnosis and 30% received
      surgical treatment. DISCUSSION: Although larger studies are required, we have
      preliminary evidence that information learned from Caucasian-predominant studies
      may not apply to all patients of laryngomalacia. When ethnically diverse infants
      are represented, a strong association between male gender and laryngomalacia does
      not appear to exist. Our data suggests that premature African-American and
      Hispanic infants are at greater risk for laryngomalacia. In addition, African
      American infants of all gestational ages may be at greater risk. Low birth weight
      may be a strong predictor of laryngomalacia regardless of the patient's gender or
      ethnicity.

PMID- 21955526
TI  - Endoscopic cauterization of the sphenopalatine artery in pediatric intractable
      posterior epistaxis.
AB  - OBJECTIVE: To evaluate the rule of endoscopic sphenopalatine artery cauterization
      in posterior intractable epistaxis in pediatric age group as regard technical
      difficulty, efficacy, and safety in children. STUDY DESIGN: Retrospective study.
      PATIENTS AND METHODS: From March 2008 to February 2011, 7 children (4 male, 3
      female) with idiopathic intractable posterior epistaxis, patients' age ranged
      from 8 to 14 years (10.7 average). All patients underwent preoperative laboratory
      investigations to exclude bleeding or coagulation disorders and CT paranasal
      sinus. All patients underwent endoscopic sphenopalatine artery cauterization (7
      procedures for 7 patients, 5 were in the right side and 2 were in the left side).
      RESULTS: postoperative evaluation showed no recurrence for epistaxis during the
      post operative follow up period. Also, no complications were found. The average
      follow up period was 17.8 months. CONCLUSIONS: Endoscopic cauterization of
      sphenopalatine artery in pediatric age group was effective and safe technique
      providing that the surgeon has a good experience regarding pediatric endoscopic
      sinonasal anatomy. Minimal endoscopic technique in this age group is important to
      avoid unnecessary operative and postoperative complications. Avoid excessive
      cauterization to lateral nasal wall in this technique is crucial to avoid
      unexpected nerve injury or tissue necrosis.

PMID- 21955528
TI  - The use of myristic acid as a ligand of polyethylenimine/DNA nanoparticles for
      targeted gene therapy of glioblastoma.
AB  - To establish a gene delivery system for brain targeting, a low molecular weight
      polyethylenimine (PEI(10 K))  was modified with myristic acid (MC), and complexed
      with DNA, yielding MC-PEI(10 K)/DNA  nanoparticles successfully. The
      nanoparticles were observed to be successfully taken up by the brains of mice.
      The transfection efficiency of the nanoparticles was then investigated, and both
      the in vitro and in vivo gene expression of MC-PEI(10 K)/DNA  nanoparticles is
      significantly higher than that of unmodified PEI(10 K)/DNA  nanoparticles. The
      anti-glioblastoma effect of MC-PEI(10 K)/pORF-hTRAIL was demonstrated by the
      survival time of intracranial U87 glioblastoma-bearing mice. The median survival
      time of the MC-PEI(10 K)/pORF-hTRAIL group (28 days) was significantly longer
      than that of the PEI(10 K)/pORF-hTRAIL group (24 days), the MC-PEI(10 K)/pGL(3) 
      group (21 days) and the saline group (22 days). Therefore, our results suggested
      that MC-PEI(10 K)  could be potentially used for brain-targeted gene delivery and
      in the treatment of glioblastoma.

PMID- 21955527
TI  - Using web-based and paper-based questionnaires for collecting data on fertility
      issues among female childhood cancer survivors: differences in response
      characteristics.
AB  - BACKGROUND: Web-based questionnaires have become increasingly popular in health
      research. However, reported response rates vary and response bias may be
      introduced. OBJECTIVE: The aim of this study was to evaluate whether sending a
      mixed invitation (paper-based together with Web-based questionnaire) rather than
      a Web-only invitation (Web-based questionnaire only) results in higher response
      and participation rates for female childhood cancer survivors filling out a
      questionnaire on fertility issues. In addition, differences in type of response
      and characteristics of the responders and nonresponders were investigated.
      Moreover, factors influencing preferences for either the Web- or paper-based
      version of the questionnaire were examined. METHODS: This study is part of a
      nationwide study on reproductive function, ovarian reserve, and risk of premature
      menopause in female childhood cancer survivors. The Web-based version of the
      questionnaire was available for participants through the Internet by means of a
      personalized user name and password. Participants were randomly selected to
      receive either a mixed invitation (paper-based questionnaire together with log-in
      details for Web-based questionnaire, n = 137) or a Web-only invitation (log-in
      details only, n = 140). Furthermore, the latter group could request a paper-based
      version of the questionnaire by filling out a form. RESULTS: Overall response
      rates were comparable in both randomization groups (83% mixed invitation group vs
      89% in Web-only invitation group, P = .20). In addition, participation rates
      appeared not to differ (66% or 90/137, mixed invitation group vs 59% or 83/140,
      Web-only invitation group, P =.27). However, in the mixed invitation group,
      significantly more respondents filled out the paper-based questionnaire compared
      with the Web-only invitation group (83% or 75/90 and 65% or 54/83, respectively,
      P = .01). The 44 women who filled out the Web-based version of the questionnaire
      had a higher educational level than the 129 women who filled out the paper-based
      version (P = .01). Furthermore, the probability of filling out the Web-based
      questionnaire appeared to be greater for women who were allocated to the Web-only
      invitation group (OR = 2.85, 95% CI 1.31-6.21), were older (OR = 1.08, 95% CI
      1.02-1.15), had a higher educational level (OR high vs low = 0.06, 95% CI 0.01
      0.52), or were students (OR employed vs student = 3.25, 95% CI 1.00-10.56).
      CONCLUSIONS: Although overall response as well as participation rates to both
      types of invitations were similar, adding a paper version of a questionnaire to a
      Web-only invitation resulted in more respondents filling out the paper-based
      version. In addition, women who were older, had a higher level of education, or
      were students, were more likely to have filled out the Web-based version of the
      questionnaire. Given the many advantages of Web-based over paper-based
      questionnaires, researchers should strongly consider using Web-based
      questionnaires, although possible response bias when using these types of
      questionnaires should be taken into account. TRIAL REGISTRATION: Nederlands Trial
      Register NTR2922; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2922
      (Archived by WebCite at http://www.webcitation.org/5zRRdMrDv).

PMID- 21955529
TI  - Laparoscopic adrenalectomy in children.
AB  - PURPOSE: Reporting on the laparoscopic technique for adrenal disease in children
      and adolescents has been limited. We review here our experience with laparoscopic
      adrenal surgery in children. PATIENTS AND METHODS: 19 laparoscopic unilateral
      adrenalectomies were performed in 10 girls and 7 boys (mean age 3.9 years) during
      1998-2011. The clinical diagnosis before surgery was virilizing tumor (n = 8),
      pheochromocytoma (n = 3), nonfunctioning solid adrenal tumor (n = 3), mixed
      adrenocortical tumor (n = 2), cystic adrenal mass (n = 1). Unilateral adrenal
      lesions were 20-65 mm at the longest axis on computerized tomography (12 right
      side, 7 left side). RESULTS: The final clinicopathological diagnosis was cortical
      adenoma (n = 9), pheochromocytoma (n = 3, bilateral in two), neuroblastoma (n =
      1), ganglioneuroblastoma (n = 1), ganglioneuroma (n = 1), adrenocortical
      carcinoma (n = 1), benign adrenal tissue (n = 1). Average operative time was
      138.5 min (range 95-270). Blood transfusion was required in one case (5%). No
      conversion to open surgery was required and no deaths or postoperative
      complications occurred. Average hospital stay was 3.5 days (range 2-15). Average
      postoperative follow-up was 81 months (range 2-144). Two contralateral
      metachronic pheochromocytomas associated with von Hippel-Lindau syndrome
      occurred, treated with partial laparoscopic adrenalectomy (one without
      postoperative need of cortisone replacement therapy). CONCLUSIONS: Laparoscopic
      adrenalectomy is a feasible procedure that produces good results. It can be used
      safely to treat suspected benign and malignant adrenal masses in children with
      minimal morbidity and short hospital stay.

PMID- 21955530
TI  - "Whatever you are, be a good one": osteopathic identity, equality, and the
      California merger.

PMID- 21955531
TI  - "Whatever you are, be a good one": osteopathic identity, equality, and the
      California merger.

PMID- 21955532
TI  - An osteopathic approach to type 2 diabetes mellitus.
AB  - The prevalence of type 2 diabetes mellitus (T2DM) has reached epidemic
      proportions in the United States, the impact of which is seen in all medical
      practices. The tenets of osteopathic medicine are readily applicable to a
      proactive approach to patients with T2DM and are (1) the body is a unit; the
      person is a unit of body, mind, and spirit; (2) the body is capable of self
      regulation, self-healing, and health maintenance; (3) structure and function are
      reciprocally interrelated; and (4) rational treatment is based upon an
      understanding of these basic principles. The authors examine the evidence that
      supports the application of these tenets to the prevention and management of T2DM
      and cover topics including the removal of noxious stimuli to help the body
      function optimally; the musculoskeletal system's role in disease prevention and
      management; the dynamic interaction of body, mind, and spirit, all 3 of which
      must be addressed to maintain health and limit disease; and intrinsic and
      extrinsic forces that can either promote or provoke a person's health.

PMID- 21955533
TI  - Contribution of osteopathic medicine to care of patients with chronic wounds.
AB  - Since its inception, osteopathic medicine has been concerned with the lymphatic
      system. Research has demonstrated the effectiveness of lymphatic osteopathic
      manipulative treatment (OMT) techniques in affecting fluid management and immune
      function. Many of the functions provided by the lymphatic system and augmented by
      OMT are necessary for proper wound healing. The authors highlight the unique
      contribution of the lymphatics to wound healing, as well as the unique
      contribution of OMT to lymphatic-directed treatment of patients with chronic
      wounds. The authors propose that this information be used as a basis for research
      into the effects of OMT on chronic wound healing in patients.

PMID- 21955534
TI  - Ultrasonography-guided osteopathic manipulative treatment for a patient with
      thoracic outlet syndrome.
AB  - Patients with thoracic outlet syndrome can be treated with osteopathic
      manipulative treatment (OMT) to alleviate dysfunction and restriction of the
      pectoralis minor muscle (PMM) and the resulting compression of the brachial
      plexus. Neuromuscular ultrasonography (US) can demonstrate abnormalities in the
      thoracic outlet that are amenable to OMT and can be used to monitor intervention.
      The present report identifies PMM deformation and brachial plexus compression in
      a 32-year-old woman with thoracic outlet syndrome who was treated successfully
      with OMT. Neuromuscular US results were used to measure the degree of PMM
      deformation with the pectoral bowing ratio and confirm the diagnosis. Osteopathic
      manipulative treatment was applied and monitored using neuromuscular US to
      confirm that the operator's manipulating hand had direct contact with the PMM.
      Symptoms abated immediately after treatment. Results of a second neuromuscular US
      examination showed that the pectoral bowing ratio decreased into the normal range
      and thus confirmed that PMM deformation had resolved.

PMID- 21955535
TI  - Elevated chromium levels and prosthetic joint implants.
AB  - Chromium is a naturally occurring, toxic heavy metal used in many industrial
      processes. The U.S. Department of Labor's Occupational Safety and Health
      Administration has established specific limits for occupational exposure levels
      of chromium and guidelines for medical surveillance of individuals who have been
      exposed to chromium. The author presents a case in which a 54-year-old man who
      had been working with chromium exhibited persistent elevations of urinary
      chromium levels after the cessation of occupational exposure. The author
      determined that the elevated chromium levels were caused by the patient's knee
      prostheses, which were made of cobalt-chromium alloy. The author also discusses
      mandates and screening guidelines for occupational chromium exposure and reviews
      the literature on chromium levels in individuals with prosthetic joint implants.

PMID- 21955536
TI  - Syncope masquerading as a fall with seizure activity.

PMID- 21955538
TI  - The use of LiDCO based fluid management in patients undergoing hip fracture
      surgery under spinal anaesthesia: neck of femur optimisation therapy - targeted
      stroke volume (NOTTS): study protocol for a randomized controlled trial.
AB  - BACKGROUND: Approximately 70,000 patients/year undergo surgery for repair of a
      fractured hip in the United Kingdom. This is associated with 30-day mortality of
      9% and survivors have a considerable length of acute hospital stay
      postoperatively (median 26 days). Use of oesophageal Doppler monitoring to guide
      intra-operative fluid administration in hip fracture repair has previously been
      associated with a reduction in hospital stay of 4-5 days. Most hip fracture
      surgery is now performed under spinal anaesthesia. Oesophageal Doppler monitoring
      may be unreliable in the presence of spinal anaesthesia and most patients would
      not tolerate the probes. An alternative method of guiding fluid administration
      (minimally-invasive arterial pulse contour analysis) has been shown to reduce
      length of stay in high-risk surgical patients but has never been studied in hip
      fracture surgery. METHODS: Single-centre randomised controlled parallel group
      trial. Randomisation by website using computer generated concealed tables.
      SETTING: University hospital in UK. PARTICIPANTS: 128 patients with acute primary
      hip fracture listed for operative repair under spinal anaesthesia and aged > 65
      years. INTERVENTION: Stroke volume guided intra-operative fluid management.
      Continuous measurement of SV recorded by a calibrated cardiac output monitor
      (LiDCOplus). Maintenance fluid and 250 ml colloid boluses given to achieve
      sustained 10% increases in stroke volume. CONTROL GROUP: fluid administration at
      the responsible (blinded) anaesthetist's discretion. The intervention terminates
      at the end of the surgical procedure and post-operative fluid management is at
      the responsible anaesthetist's discretion. PRIMARY OUTCOME: length of acute
      hospital stay is determined by a blinded team of clinicians. Secondary outcomes
      include number of complications and total cost of care. Funding NIHR/RfPB: PB-PG
      0407-13073. TRIAL REGISTRATION NUMBER:  TRIAL REGISTRATION: Current Controlled
      Trials ISRCTN88284896.

PMID- 21955539
TI  - [Surgical approach to endovascular cardiac resynchronisation after failure].

PMID- 21955540
TI  - [Cardiomyopathy and inborn errors of metabolism in children. Study of 12 cases].
AB  - BACKGROUND AND OBJECTIVE: Cardiomyopathy in childhood is a rare entity. Inborn
      errors of metabolism can cause myocardial involvement by several mechanisms.
      PATIENTS AND METHODS: Patients under 16 years diagnosed with cardiomyopathy and
      EIM in a period of 11 years (1998-2009) were included. RESULTS: A total of 12
      patients were studied (8% of all cardiomyopathies), 9 boys and three girls, with
      a median age at diagnosis of 6 months (range: birth-8.8 years). Fifty percent had
      an onset with cardiac symptoms and heart failure was associated with an earlier
      diagnosis of the disease (P<.05). On ultrasound 10 patients had ventricular
      hypertrophy, which was associated with mitochondrial and lysosomal disease; only
      2 patients had ventricular dilatation, which was associated with altered fatty
      acid metabolism (P<.05). The median survival was 5 months (range: 2-11 months).
      No variable was significantly associated with the likelihood of death.
      CONCLUSIONS: Patients with heart failure at onset are diagnosed earlier (before 3
      months of life). Echocardiography helps in the diagnosis and monitoring of
      metabolic disease.

PMID- 21955542
TI  - Floating-Harbor Syndrome:  report on a case in a mother and daughter, further
      evidence of autosomal dominant inheritance.
AB  - Floating-Harbor Syndrome is a growth retardation syndrome with delayed bone age,
      typical facial features, and retarded speech development of unknown etiology.
      Very few familial cases have been reported. We report on the fourth case in a
      mother and daughter, suggesting autosomal dominant inheritance.

PMID- 21955541
TI  - Trends in the clinical characteristics of HIV-infected patients initiating
      antiretroviral therapy in Kenya, Uganda and Tanzania between 2002 and 2009.
AB  - BACKGROUND: East Africa has experienced a rapid expansion in access to
      antiretroviral therapy (ART) for HIV-infected patients. Regionally representative
      socio-demographic, laboratory and clinical characteristics of patients accessing
      ART over time and across sites have not been well described. METHODS: We
      conducted a cross-sectional analysis of characteristics of HIV-infected adults
      initiating ART between 2002 and 2009 in Kenya, Uganda and Tanzania and in the
      International Epidemiologic Databases to Evaluate AIDS Consortium.
      Characteristics associated with advanced disease (defined as either a CD4 cell
      count level of less than 50 cells/mm3 or a WHO Stage 4 condition) at the time of
      ART initiation and use of stavudine (D4T) or nevirapine (NVP) were identified
      using a log-link Poisson model with robust standard errors. RESULTS: Among 48,658
      patients (69% from Kenya, 22% from Uganda and 9% from Tanzania) accessing ART at
      30 clinic sites, the median age at the time of ART initiation was 37 years (IQR:
      31-43) and 65% were women. Pre-therapy CD4 counts rose from 87 cells/mm3 (IQR: 26
      161) in 2002-03 to 154 cells/mm3 (IQR: 71-233) in 2008-09 (p<0.001). Accessing
      ART at advanced disease peaked at 35% in 2005-06 and fell to 27% in 2008-09. D4T
      use in the initial regimen fell from a peak of 88% in 2004-05 to 59% in 2008-09,
      and a greater extent of decline was observed in Uganda than in Kenya and
      Tanzania. Self-pay for ART peaked at 18% in 2003, but fell to less than 1% by
      2005. In multivariable analyses, accessing ART at advanced immunosuppression was
      associated with male sex, women without a history of treatment for prevention of
      mother to child transmission (both as compared with women with such a history)
      and younger age after adjusting for year of ART initiation and country of
      residence. Receipt of D4T in the initial regimen was associated with female sex,
      earlier year of ART initiation, higher WHO stage, and lower CD4 levels at ART
      initiation and the absence of co-prevalent tuberculosis. CONCLUSIONS: Public
      health ART services in east Africa have improved over time, but the fraction of
      patients accessing ART with advanced immunosuppression is still high, men
      consistently access ART with more advanced disease, and D4T continues to be
      common in most settings. Strategies to facilitate access to ART, overcome
      barriers among men and reduce D4T use are needed.

PMID- 21955544
TI  - Barriers to effective discharge planning: a qualitative study investigating the
      perspectives of frontline healthcare professionals.
AB  - ABSTRACT:  BACKGROUND: Studies have shown that effective discharge planning is
      one of the key factors related to the quality of inpatient care and unnecessary
      hospital readmission. The perception and understanding of hospital discharge by
      health professionals is important in developing effective discharge planning. The
      aims of this present study were to explore the perceived quality of current
      hospital discharge from the perspective of health service providers and to
      identify barriers to effective discharge planning in Hong Kong. METHODS: Focus
      groups interviews were conducted with different healthcare professionals who were
      currently responsible for coordinating the discharge planning process in the
      public hospitals. The discussion covered three main areas: current practice on
      hospital discharge, barriers to effective hospital discharge, and suggested
      structures and process for an effective discharge planning system. RESULTS:
      Participants highlighted that there was no standardized hospital-wide discharge
      planning and policy-driven approach in public health sector in Hong Kong.
      Potential barriers included lack of standardized policy-driven discharge planning
      program, and lack of communication and coordination among different health
      service providers and patients in both acute and sub-acute care provisions which
      were identified as mainly systemic issues. Improving the quality of hospital
      discharge was suggested, including a multidisciplinary approach with clearly
      identified roles among healthcare professionals. Enhancement of health
      professionals' communication skills and knowledge of patient psychosocial needs
      were also suggested. CONCLUSIONS: A systematic approach to develop the structure
      and key processes of the discharge planning system is critical in ensuring the
      quality of care and maximizing organization effectiveness. In this study,
      important views on barriers experienced in hospital discharge were provided.
      Suggestions for building a comprehensive, system-wide, and policy-driven
      discharge planning process with clearly identified staff roles were raised.
      Communication and coordination across various healthcare parties and provisions
      were also suggested to be a key focus.

PMID- 21955545
TI  - Outcome of surgery for colonoscopic perforation.
AB  - AIM: The aetiology of colonoscopic perforation and factors related to poor
      outcome of surgical treatment were studied. METHOD: A single-centre review was
      conducted of all patients who underwent surgical treatment of a colonoscopic
      perforation, identified from a prospective registry of 21,981 consecutive
      colonoscopies carried out between 1993 and 2009. RESULTS: There were 29 (eight
      women) patients of mean age 73 years including 10 who had a nonelective
      colonoscopy. The perforation was not immediately recognized in 12 patients and in
      the remaining 17, seven were initially managed conservatively. The causes of
      perforation were barotrauma (11), mechanical force (14) and polypectomy-related
      (3). Barotrauma was more frequent in emergency colonoscopy and mechanical force
      in elective colonoscopy. The outcome of surgery was as follows: mortality 10%,
      complications 34.5%, reoperation 14%, secondary surgery 23% and permanent
      colostomy 3%. The only factor related to in-hospital mortality was an increased
      American Society of Anesthesiologists (ASA) score. CONCLUSION: Colonoscopic
      perforation requiring surgery is a catastrophic event with high mortality,
      morbidity and reoperation rates.

PMID- 21955546
TI  - Enhancement of cutaneous immune response to bacterial infection after low-level
      light therapy with 1072 nm infrared light: a preliminary study.
AB  - We investigated the photobiomodulation effects of 1072 nm infrared light on the
      natural immune response involved in anti-bacterial and wound healing processes.
      Thirty mice infected with MRSA on the skin were divided into two groups. The
      experimental group was treated with 1072 nm infrared light (irradiance: 20
      mW/cm(2), fluence: 12 J/cm(2) for 10 min) at 2, 4, 8, 12, 24 h, 3 and 5 days
      after inoculation and the control group with sham light. Serial changes of the
      mRNA levels of TLR2, IL-1beta, TNF-alpha, IL-6, iNOS, MCP-1, TGF-beta, bFGF and
      VEGF were studied by real time RT-PCR and those of the expression level of VEGF,
      bFGF, TGF-beta and NF-kappaB by immunohistochemistry. The mRNA levels of the
      cytokines involved in the early phase of anti-bacterial immune response (IL
      1beta, TNF-alpha, IL-6, MCP-1) increased significantly in the 1072 nm group,
      peaking between 12 and 24 h post-inoculation. These levels normalized after 3-5
      days. Immunohistochemistry revealed a notably stronger expression of VEGF in the
      1072 nm group from 8-h post-inoculation to 5-day post-inoculation. We concluded
      that 1072 nm infrared light had a photobiomodulation effect which resulted in an
      enhanced biological immune response to the bacterial infection by MRSA and also
      increased the expression of VEGF to a significant level.

PMID- 21955548
TI  - Sub-threshold signal processing in arrays of non-identical nanostructures.
AB  - Weak input signals are routinely processed by molecular-scaled biological
      networks composed of non-identical units that operate correctly in a noisy
      environment. In order to show that artificial nanostructures can mimic this
      behavior, we explore theoretically noise-assisted signal processing in arrays of
      metallic nanoparticles functionalized with organic ligands that act as tunneling
      junctions connecting the nanoparticle to the external electrodes. The electronic
      transfer through the nanostructure is based on the Coulomb blockade and tunneling
      effects. Because of the fabrication uncertainties, these nanostructures are
      expected to show a high variability in their physical characteristics and a
      diversity-induced static noise should be considered together with the dynamic
      noise caused by thermal fluctuations. This static noise originates from the
      hardware variability and produces fluctuations in the threshold potential of the
      individual nanoparticles arranged in a parallel array. The correlation between
      different input (potential) and output (current) signals in the array is analyzed
      as a function of temperature, applied voltage, and the variability in the
      electrical properties of the nanostructures. Extensive kinetic Monte Carlo
      simulations with nanostructures whose basic properties have been demonstrated
      experimentally show that variability can enhance the correlation, even for the
      case of weak signals and high variability, provided that the signal is processed
      by a sufficiently high number of nanostructures. Moderate redundancy permits us
      not only to minimize the adverse effects of the hardware variability but also to
      take advantage of the nanoparticles' threshold fluctuations to increase the
      detection range at low temperatures. This conclusion holds for the average
      behavior of a moderately large statistical ensemble of non-identical
      nanostructures processing different types of input signals and suggests that
      variability could be beneficial for signal processing. We demonstrate also that
      circuits composed of coupled non-identical nanoparticles can act as elementary
      nano-oscillators that show synchronization properties for sub-threshold stimuli.
      The results obtained should be of conceptual interest for the design of reliable
      signal processing schemes with non-identical nanostructures.

PMID- 21955547
TI  - Protection of protease-activated receptor 2 mediated vasodilatation against
      angiotensin II-induced vascular dysfunction in mice.
AB  - BACKGROUND: Under conditions of cardiovascular dysfunction, protease-activated
      receptor 2 (PAR2) agonists maintain vasodilatation activity, which has been
      attributed to increased cyclooxygenase-2, nitric oxide synthase and calcium
      activated potassium channel (SK3.1) activities. Protease-activated receptor 2
      agonist mediated vasodilatation is unknown under conditions of dysfunction caused
      by angiotensin II. The main purpose of our study was to determine whether PAR2
      induced vasodilatation of resistance arteries was attenuated by prolonged
      angiotensin II treatment in mice. We compared the vasodilatation of resistance
      type arteries (mesenteric) from angiotensin II-treated PAR2 wild-type mice (WT)
      induced by PAR2 agonist 2-furoyl-LIGRLO-amide (2fly) to the responses obtained in
      controls (saline treatment). We also investigated arterial vasodilatation in
      angiotensin II-treated PAR2 deficient (PAR2-/-) mice. RESULTS: 2fly-induced
      relaxations of untreated arteries from angiotensin II-treated WT were not
      different than saline-treated WT. Treatment of arteries with nitric oxide
      synthase inhibitor and SK3.1 inhibitor (L-NAME + TRAM-34) blocked 2fly in
      angiotensin II-treated WT. Protein and mRNA expression of cyclooxygenase-1 and -2
      were increased, and cyclooxygenase activity increased the sensitivity of arteries
      to 2fly in only angiotensin II-treated WT. These protective vasodilatation
      mechanisms were selective for 2fly compared with acetylcholine- and nitroprusside
      induced relaxations which were attenuated by angiotensin II; PAR2-/- were
      protected against this attenuation of nitroprusside. CONCLUSIONS: PAR2-mediated
      vasodilatation of resistance type arteries is protected against the negative
      effects of angiotensin II-induced vascular dysfunction in mice. In conditions of
      endothelial dysfunction, angiotensin II induction of cyclooxygenases increases
      sensitivity to PAR2 agonist and the preserved vasodilatation mechanism involves
      activation of SK3.1.

PMID- 21955549
TI  - Brief report: self-harm is associated with immature defense mechanisms but not
      substance use in a nonclinical Scottish adolescent sample.
AB  - It has been unclear whether adolescent deliberate self-harm (DSH) is more
      associated with substance use or with characterological impairments. Multivariate
      determination of (N = 114 Scottish adolescents) ever engaging in DSH (Youth Risk
      Behavior Survey) from alcohol use, other substance use, and immature defense
      mechanism use (Defense Style Questionnaire; DSQ-40) revealed that a history of
      DSH was associated with more use of immature defense mechanisms by not with
      substance use or recent alcohol use. More research and clinical attention might
      be given to immature defense mechanisms in cases of DSH.

PMID- 21955550
TI  - [Acute type-B aortic dissection associated with isthmic coarctation in adult].
AB  - The authors report a case of acute type-B aortic dissection in association with
      an unknown isthmic coarctation in a 30-year-old adult. Successful surgical repair
      was performed 6 months later without cardiopulmonary bypass. Physiopathological
      aspects and surgical strategy are discussed. Acute aortic dissection distal to
      isthmic coarctation is extremely rare and has been reported in only 5 other
      cases. Present case is the first, to our knowledge, to be operated without
      cardiopulmonary bypass.

PMID- 21955551
TI  - Failure to report protocol violations in clinical trials: a threat to internal
      validity?
AB  - BACKGROUND: Excessive protocol violations (PV), which can be defined as
      preventable mistakes in study conduct, may result in patient harm and introduce
      errors into a clinical trial's results leading to flawed trial conclusions.The
      purpose of this project was to gain a better understanding of reported PVs, to
      describe current practice with regards to the use of methods for the reduction of
      PVs and to investigate relationships between clinical trial characteristics and
      PVs. METHODS: We reviewed 80 clinical trials conducted across a broad range of
      medical specialties published in four major general medical journals (The Lancet,
      NEJM, JAMA, BMJ). Eligible papers were identified using a PubMed search. For each
      included trial, two authors independently abstracted information on trial
      characteristics, PV reporting and PV rates and interventions used to reduce PVs.
      PVs were categorised into one of five distinct types: enrollment, randomisation,
      study intervention, patient compliance and data collection errors. Associations
      between PVs and study characteristics were investigated using logistic
      regression. RESULTS: Eighty clinical trials (20 from each journal) were
      identified from 101 consecutive PubMed abstracts. The median number of
      participants was 701 (range: 20 to 162, 367) and the median number of
      participating sites was 15 (range: 1 to 701). Nineteen percent (15/80) of
      included trials were single centre trials. The median study duration was 24
      months (range: 5.81 - 127 months) and 74% (59/80) of included trials were
      primarily academic funded.Thirty two percent (26/80) of included trials failed to
      provide explicit reporting of any type of PV and none (0/80) of the trials
      provided explicit reporting of all five types of PVs. Larger clinical trials
      (more patients, more sites, longer duration, more complex management structure)
      were more likely to have more complete reporting of PV's.Only 9% (7/80) of trials
      reported the use of a specific study method to prevent PVs. Use of a run-in phase
      was the only method reported. CONCLUSIONS: PVs are under-reported. Although the
      CONSORT statement provides guidance on the reporting of PVs, reporting
      requirements are not explicit for all types of PVs. As a first step towards
      improved reporting by authors, we recommend the CONSORT statement highlight the
      importance of PVs by making reporting requirements more explicit.

PMID- 21955552
TI  - The impact of cataract on the quantitative, non-invasive assessment of retinal
      blood Flow.
AB  - PURPOSE: The aim of the study was to determine the impact of cataract on the
      quantitative, non-invasive assessment of retinal blood flow assessed by
      bidirectional laser Doppler flowmetry and simultaneous vessel densitometry.
      METHODOLOGY: Ten patients scheduled for extracapsular cataract extraction using
      phacoemulsification and intraocular lens implantation between the ages of 61 and
      84 (mean age 73 years, SD +/- 8) were prospectively recruited. Two visits were
      required to complete the study; one visit prior to extracapsular cataract
      extraction and one at least 6 weeks after the surgery to allow for sufficient
      postoperative recovery. The severity of cataract was documented using the Lens
      Opacity Classification System (LOCS, III) at the first visit. Retinal arteriolar
      hemodynamics were measured at both visits using the high-intensity setting of the
      Canon Laser Blood Flowmeter. RESULTS: All eyes showed no clinical signs of
      postoperative intraocular inflammation. The quantitative assessment of retinal
      arteriolar diameter and blood flow were reduced following extracapsular cataract
      extraction (Wilcoxon signed-rank test, p = 0.022 and p=0.028, respectively);
      however, centreline blood velocity was not significantly changed (Wilcoxon signed
      rank test, p=0.074). Intraocular pressure was unchanged pre- and postcataract
      extraction. CONCLUSIONS: Retinal vessel densitometry assessment in the presence
      of cataract results in the erroneous elevation of the diameter measurement and
      thereby the calculation of blood flow. The bidirectional Doppler assessment of
      blood velocity appears to be more robust to light scatter induced by cataract.
      Care needs to be exercised in the interpretation of studies of retinal vessel
      diameter or blood flow that utilize similar densitometry techniques.

PMID- 21955553
TI  - Modern surgical management of tongue carcinoma - a clinical retrospective
      research over a 12 years period.
AB  - OBJECTIVES: In this retrospective study, we present a clinical review of our
      experience with tongue cancer in order to obtain valid criteria for therapeutic
      decision-making. MATERIALS AND METHODS: Between August 1999 and June 2011, a
      total of 398 patients with squamous cell carcinoma of the tongue were treated at
      the Department of Oral and Maxillofacial Surgery, King Edward Medical University
      Lahore Pakistan. Data concerning patient characteristics, clinical and pathologic
      tumour characteristics and treatment strategies and their results were obtained
      from a retrospective review of medical records. The average follow-up was 4.6
      years. Statistical analysis for survival was calculated by the method of Kaplan
      and Meier. RESULTS: There were 398 total patients. The mean age at diagnosis was
      49.5 years,. 224 (56.3%) were male and 174 (43.7%) female (male/female ratio =
      1.3:1).332/398 patients received surgical treatment, whereas 66 patients were
      excluded from surgical treatment and received primary radio (chemo) therapy after
      biopsy. Tongue carcinoma patients treated by non surgical treatment modalities
      had 5 years survival rate of 45.5% and patients with surgical intervention had
      survival rate of 96.1%. CONCLUSIONS: We recommend categorical bilateral neck
      dissection in order to reliably remove occult lymph node metastases. Adjuvant
      treatment modalities should be applied more frequently in controlled clinical
      trials and should generally be implemented in cases with unclear margins and
      lymphatic spread. CLINICAL RELEVANCE: This study provides modern treatment
      strategies for the tongue carcinoma.

PMID- 21955554
TI  - Inactivation of CD73 promotes atherogenesis in apolipoprotein E-deficient mice.
AB  - AIMS: CD73 (ecto-5'-nucleotidase) is expressed by a broad range of immune cells
      and attenuates inflammation in several acute disease models. This study therefore
      explored the role of CD73-derived adenosine in a model of chronic vascular
      inflammation such as atherogenesis. METHODS AND RESULTS: CD73(-/-) mice were
      backcrossed into the apolipoprotein E (ApoE(-/-)) background. In CD73(-/-)/ApoE(
      /-) double mutants, atherosclerotic lesion formation was increased by ~50%
      compared with ApoE(-/-). However, the cellular composition and extracellular
      matrix of the plaques did not differ. Surprisingly, we found significant activity
      and expression of CD73 in the plaque of ApoE(-/-) mice which increased over time.
      CD73 co-localized with macrophages, Tregs, and cells of mesenchymal origin.
      Genome-wide microarray analysis of the aorta lacking CD73 revealed upregulation
      of endothelin-1 (Edn1) mRNA together with changes of genes in lipid metabolism
      and the Wnt and nuclear factor kappa B pathways. Measurement of plasma levels
      verified the upregulation of Edn1 in CD73(-/-) and double mutants. Plasma
      triglycerides (TG) were also found to be significantly elevated in the CD73(-/
      )/ApoE(-/-) mice compared with ApoE(-/-) controls. CONCLUSION: Lack of CD73
      promotes atherogenesis most likely by de-inhibition of resident macrophages and T
      cells. Elevated Edn1 and TG levels may have contributed. This establishes CD73
      derived adenosine as a direct or indirect regulator of atherogenesis.

PMID- 21955555
TI  - [Rare kidney stones].

PMID- 21955556
TI  - [Cystitis and ketamine associated bladder dysfunction].
AB  - OBJECTIVES: To analyze the prevalence of lower urinary tract symptoms (LUTS) in
      recreational ketamine users and evaluate its relationship with the consumption
      pattern. MATERIAL AND METHODS: Evaluation of 13 ketamine users. The presence of
      LUTS, gross hematuria and lumbar spine pain was analyzed. The ketamine usage
      pattern was recorded: initiation, administration route, dose in the last month
      and frequency of usage. RESULTS: Six patients (46%) reported LUTS, with daily
      mean micturations every 42 minutes and nighttime of 3 episodes, with dysuria
      (100%), urgency (100%), incontinence (20%), decreased flow (80%), hypogastric or
      perineal pain (80%), gross hematuria (80%) and bilateral lumbar spine pain (40%).
      Symptomatic patients described a mean intake of inhaled ketamine of 3g/day (SD
      2), 80% with a daily frequency and the asymptomatic ones of 1.03 g/day (SD 0.92)
      limited to weekends. The mean consumption time to the appearance of the symptoms
      was 31 months (SD 16.29). Intensity of the symptoms was related with the ketamine
      dose and improved on increasing water intake. CONCLUSIONS: There seems to be a
      relationship between the picture with the dose and frequency of consumption,
      there being factors that reinforce the hypothesis that this action of the drug is
      due to the harmful effect on the urothelium. The process to identify it on time
      should be known, since the only known effective measure is to stop the
      consumption in the initial phases.

PMID- 21955558
TI  - [High-pressure balloon dilatation for treatment of orthotopic ureterocele].
AB  - OBJECTIVE: Transurethral puncture or endoscopic unroofing is the best treatment
      currently used for both orthotopic and ectopic ureteroceles. However, they have a
      high incidence of secondary vesicoureteral reflux and subsequent procedures in
      both groups. We present a new technique for treatment of orthotopic ureterocele.
      MATERIAL AND METHODS: We have analyzed 4 patients with orthotopic ureterocele
      (9.7 +/- 6.2 months old) treated by dilatation of the meatus of the ureterocele.
      No patient had vesicoureteral reflux or duplicate systems. The indication was
      pyonephrosis in 2 children and progressive worsening of hydronephrosis in 2.
      Dilatation was performed with 5 or 6mm high-pressure balloon after inserting a
      stent with guidewire of 0.014" to the ureterocele. RESULTS: There were no
      intraoperative or postoperative complications, surgical time being 24 +/-
      9minutes. All patients were discharged at 24 postoperative hours.
      Ureterohydronephrosis disappeared in all the children and they continue
      asymptomatic after 35 +/- 22.5 months of follow-up. There were no cases of
      secondary vesicoureteral reflux and renal scan was unchanged after treatment.
      CONCLUSIONS: High pressure balloon dilatation of the meatus in cases of
      orthotopic ureterocele is a fast, safe and successful surgical technique. We did
      not find any cases of secondary vesicoureteral reflux or subsequent procedures in
      our series, so we believe this may offer significant benefits over the
      transurethral puncture in such patients.

PMID- 21955559
TI  - [Comment to "prognostic value of venous tumor thrombus in renal cell carcinoma"].

PMID- 21955560
TI  - [Partial elective nephrectomy].
AB  - INTRODUCTION: Partial nephrectomy is widely accepted as a therapeutic modality in
      renal cell carcinoma (RCC) in patients with single kidney, bilateral tumor or
      deteriorated renal function. Currently, long-term survival studies have
      consolidated partial nephrectomy as the treatment of choice for RCC in selected
      patients with normal contralateral kidney. MATERIAL AND METHODS: Between July
      1990 and January 2008, a total of 102 partial nephrectomy were performed on 100
      patients with pre-operative ultrasonography diagnosis of renal carcinoma in 94
      cases and complex renal cysts in 6 cases. The pre-operative ultrasonography size
      varied from 1.5 to 10 cm with an average of 4.85 cm. RESULTS: Tumor size was
      correlated with the pathological stage, finding tumors in stage pT1 with sizes
      less than and greater than 4 cm in 74% and 64%, respectively, and in stage pT2 of
      3.7% and 5.4%. Tumor size measured by pre-operative CT scan was compared with the
      definitive size of the pathology specimen in 93 cases (56<4 cm and 37>4 cm,
      according to the CT scan). We found high concordance, however in the larger
      tumors, there was a tendency of the CT scan to overestimate the size. A post
      operative gamma scintigraphy with DMSA was performed in 40 patients. The values
      in the tumors <4 cm (21 patients) were 12-77% (average 43.3%). In tumors between
      4 and 7 cm (17 patients), the values were 13.8-53.3% (average 37.6%) and in 2
      cases of tumors >7 cm the post-operative DMSA showed 47.5 and 51%. CONCLUSIONS:
      Partial nephrectomy is currently accepted as elective treatment in incidental
      kidney tumors less than 4 cm and it is indicated increasingly more frequently in
      larger tumors and of central localization. The finding of benign pathology in the
      anatomic-pathology specimen in up to 20% of the incidental renal tumors and low
      potential of malignancy of the possible satellite lesions in the remnant kidney
      also support nephron-sparing surgery in these tumors.

PMID- 21955561
TI  - [Obesity as risk factor for lithiasic recurrence].
AB  - OBJECTIVES: Obese patients may have special characteristics in the urinary stones
      formed, as the body mass index (BMI) may also be a predictive factor in lithiasic
      recurrence. We aim to evaluate and compare the lithiasic characteristics
      according to the different BMI categories, also considering the likelihood of
      lithiasic recurrence in presence of age and gender covariables. MATERIAL AND
      METHODS: Retrospective, cross-sectional analysis on 346 lithiasic patients, 96
      (27.7%) had low-normal weight, 151 (43.6%) overweight, and 99 (28.6%) obesity.
      The Chi-square and ANOVA tests were used. Survival analysis for the calculation
      of likelihood of lithiasic recurrence (yes/no) was made based on time on 158
      patients in whom complete resolution of the initial stone was achieved by the
      Kaplan Meier method. Comparisons between the different categories of BMI were
      made using the log-Rank, Breslow and Tarone-Ware tests. Multivariate analysis was
      also made with the Cox regression model, introducing the covariables of age and
      gender. RESULTS: A significant growing linear tendency has been demonstrated
      between multiplicity and BMI (p=0.03). The variables size and composition did not
      show significant differences between the groups. Median follow-up of 158 patients
      included in the survival analysis was 1866 days (95% CI 1602.5-2129.5). Eighteen
      (11.4%) of them recurred, without finding significant differences between groups:
      4 low-normal weight (9.8%), 10 overweight (14.1%) and 4 obese (8.7%). The
      multivariate analysis also did not show a significant influence of the BMI on
      lithiasic recurrence (p=0.86; HR =1.06; 95% CI: 0.56-2.03). CONCLUSION: A
      significant influence of BMI was shown on lithiasic multiplicity on diagnosis,
      although not on lithiasic recurrence based on time. It seems to be necessary to
      carry out studies in larger samples to calculate the true influence of BMI on
      lithiasic recurrence.

PMID- 21955562
TI  - [Experimental study with Doppler ultrasound in partial chronic obstructive
      uropathy].
AB  - INTRODUCTION: This study has aimed to assess the hemodynamic parameters, Renal
      Resistive Index (RI), Peak Systolic Velocity (PSV), End-Diastolic Velocity (EDV)
      and Blood Flow of the Renal Artery (FR) by Doppler Ultrasound for diagnosis and
      monitoring postsurgical partial chronic obstructive uropathy. MATERIAL AND
      METHODS: Fifty pigs were used. The experiment was divided into three phases.
      Phase I consisted of a duplex-Doppler evaluation of the both kidneys to determine
      the parameters under study. The ratio of each index is calculated as the
      difference between the value of study kidney and the contralateral. After, a
      fluoroscopic examination was performed by compressive cystography, excretory
      urography and retrograde ureteropyelography. Finally, a model of partial right
      ureteral obstruction was created. After six weeks of the obstructive model, Phase
      II was begun with the diagnosis of the uropathy, by means of the aforementioned
      diagnostic methods and the endourological treatment was completed. Phase III is a
      follow-up performed at 6 months of treatment using the same methods as in the
      previous phases. RESULTS: Of the parameters studied, the EDV and its ratio showed
      greater sensitivity and specificity as a diagnostic marker of obstructive
      uropathy. In the postoperative monitoring, it was observed that the RI and the
      EDV returned to baseline levels, with the baseline values. CONCLUSIONS: The
      DeltaEDV and its ratio is the parameter that shows the greater efficacy for the
      diagnosis of chronic partial obstructive uropathy, however, it is insufficient to
      avoid conventional diagnostic techniques. All the parameters, mainly the EDV,
      have proven useful as complementary tests for monitoring after endourologic
      resolution of obstructive uropathy.

PMID- 21955563
TI  - [Acute urinary retention in young adult and middle-aged males due to calculi in
      the urethra: a single centre experience from North India].
AB  - OBJECTIVE: To present our experience of managing acute urinary retention (AUR) in
      young and middle-aged male due to stone/s in the urethra at a tertiary care
      centre. MATERIAL AND METHODS: Between July 2004 to April 2011, 102 male patients,
      young and middle-aged (18-40 years), who suffered from AUR due to calculus in the
      urethra were managed at our center. Initial management consisted of urethral
      catheterization or suprapubic trocar cystostomy. Definitive management was
      performed immediately or after a couple of days depending upon the availability
      of anesthesia and/or operation theatre. Stone was fragmented by mechanical
      lithotrite, pneumatic lithotrite or holmium:YAG laser. RESULTS: All the patients
      were completely free of their stone/s following the definitive procedure. Voiding
      trial was successful in all the cases. Postoperative urinary tract infection was
      observed in eight patients who had undergone immediate endoscopic management.
      Mild hematuria for approximately 48 hours was noted in six patients who underwent
      suprapubic cystolithotripsy. CONCLUSION: Endoscopic management is currently the
      treatment of choice for stone/s in the urethra which may cause AUR in young and
      middle-aged male.

PMID- 21955564
TI  - [Comment to "Results of expanded use of PCA3 score in a Spanish population with
      suspicion of prostate cancer"].

PMID- 21955565
TI  - How do we know whether the kids will really be ok? Improving our understanding of
      health care transitions.

PMID- 21955568
TI  - Regulatory T-like cells: another variation on the theme of hypomorphic mutations?

PMID- 21955567
TI  - Early and late effects of the DPP-4 inhibitor vildagliptin in a rat model of post
      myocardial infarction heart failure.
AB  - BACKGROUND: Progressive remodeling after myocardial infarction (MI) is a leading
      cause of morbidity and mortality. Recently, glucagon-like peptide (GLP)-1 was
      shown to have cardioprotective effects, but treatment with GLP-1 is limited by
      its short half-life. It is rapidly degraded by the enzyme dipeptidyl peptidase-4
      (DPP-4), an enzyme which inhibits GLP-1 activity. We hypothesized that the DPP-4
      inhibitor vildagliptin will increase levels of GLP-1 and may exert protective
      effects on cardiac function after MI. METHODS: Sprague-Dawley rats were either
      subjected to coronary ligation to induce MI and left ventricular (LV) remodeling,
      or sham operation. Parts of the rats with an MI were pre-treated for 2 days with
      the DPP-4 inhibitor vildagliptin (MI-Vildagliptin immediate, MI-VI, 15
      mg/kg/day). The remainder of the rats was, three weeks after coronary artery
      ligation, subjected to treatment with DPP-4 inhibitor vildagliptin (MI
      Vildagliptin Late, MI-VL) or control (MI). At 12 weeks, echocardiography and
      invasive hemodynamics were measured and molecular analysis and
      immunohistochemistry were performed. RESULTS: Vildagliptin inhibited the DPP-4
      enzymatic activity by almost 70% and increased active GLP-1 levels by about 3
      fold in plasma in both treated groups (p < 0.05 vs. non-treated groups). Cardiac
      function (ejection fraction) was decreased in all 3 MI groups compared with Sham
      group (p < 0.05); treatment with vildagliptin, either early or late, did not
      reverse cardiac remodeling. ANP (atrial natriuretic peptide) and BNP (brain
      natriuretic peptide) mRNA levels were significantly increased in all 3 MI groups,
      but no significant reductions were observed in both vildagliptin groups.
      Vildagliptin also did not change cardiomyocyte size or capillary density after
      MI. No effects were detected on glucose level and body weight in the post-MI
      remodeling model. CONCLUSION: Vildagliptin increases the active GLP-1 level via
      inhibition of DPP-4, but it has no substantial protective effects on cardiac
      function in this well established long-term post-MI cardiac remodeling model.

PMID- 21955569
TI  - The comprehensive assessment of local immune status of ovarian cancer by the
      clustering of multiple immune factors.
AB  - The aim of this study was to evaluate the local immune status of human ovarian
      cancers by the comprehensive analysis of tumor-infiltrating immune cells and
      immunosuppressive factors, and to elucidate the local immunity in clinical
      course. The numbers of CD1alpha+, CD4+, CD8+, CD57+, forkhead box P3+ and
      programmed cell death-1+ cells were counted, and the intensity of
      immunosuppressive factors, such as programmed cell death-1 ligand (PD-L)1, PD-L2,
      cyclooxygenase (COX)-1, COX-2 and transforming growth factor beta1, were
      evaluated in 70 ovarian cancer specimens stained by immunohistochemistry. Then
      hierarchical clustering of these parameters showed the four clusters into ovarian
      cancer cases. Cluster 1, which had significantly better prognosis than the
      others, was characterized by high infiltration of CD4+ and CD8+ cells. In
      conclusion the comprehensive analysis of local immune status led to subdivide
      ovarian cancers into groups with better or worse prognoses and may guide precise
      understanding of the local immunity.

PMID- 21955571
TI  - A new methodology for detection of counterfeit Viagra(r) and Cialis(r) tablets by
      image processing and statistical analysis.
AB  - This paper proposes a new approach for automatic classification of counterfeit
      Viagra((r)) and Cialis((r)) tablets using image processing and statistical
      analysis. A high resolution VSC 5000 is used for image acquisition in a
      controlled environment, and the combination of a thresholding technique with
      morphological operators is used to segment the tablet from the background. A
      statistical model based on the RGB color components of original samples is built,
      and the detection of counterfeit tablets was performed by checking the adherence
      of a test sample to the obtained distribution using the Bhattacharyya distance.
      Our experimental results indicated that counterfeit tablets can be effective
      detected using the proposed approach.

PMID- 21955570
TI  - Effect of an audiovisual message for tetanus booster vaccination broadcast in the
      waiting room.
AB  - BACKGROUND: General practitioners (GPs) often lack time and resources to invest
      in health education; audiovisual messages broadcast in the waiting room may be a
      useful educational tool. This work was designed to assess the effect of a message
      inviting patients to ask for a tetanus booster vaccination. METHODS: A quasi
      experimental study was conducted in a Belgian medical practice consisting of 6
      GPs and 4 waiting rooms (total: 20,000 contacts/year). A tetanus booster
      vaccination audiovisual message was continuously broadcast for 6 months in 2
      randomly selected waiting rooms (intervention group--3 GPs) while the other 2
      waiting rooms remained unequipped (control group--3 GPs). At the end of the 6
      month period, the number of vaccine adult-doses delivered by local pharmacies in
      response to GPs' prescriptions was recorded. As a reference, the same data were
      also collected retrospectively for the general practice during the same 6-month
      period of the previous year. RESULTS: During the 6-month reference period where
      no audiovisual message was broadcast in the 4 waiting rooms, the number of
      prescriptions presented for tetanus vaccines was respectively 52 (0.44%) in the
      intervention group and 33 (0.38%) in the control group (p = 0.50). By contrast,
      during the 6-month study period, the number of prescriptions differed between the
      two groups (p < 0.0001), rising significantly to 91 (0.79%) in the intervention
      group (p = 0.0005) while remaining constant in the control group (0.38% vs 0.39%;
      p = 0.90). CONCLUSIONS: Broadcasting an audiovisual health education message in
      the GPs' waiting room was associated with a significant increase in the number of
      adult tetanus booster vaccination prescriptions delivered by local pharmacies.

PMID- 21955572
TI  - Photoluminescence waveguiding in CdSe and CdTe QDs-PMMA nanocomposite films.
AB  - In this paper, active planar waveguides based on the incorporation of CdSe and
      CdTe nanocrystal quantum dots in a polymer matrix are demonstrated. In the case
      of doping the polymer with both types of quantum dots, the nanocomposite film
      guides both emitted colors, green (550 nm, CdTe) and orange (600 nm, CdSe). The
      optical pumping laser can be coupled not only with a standard end-fire coupling
      system, but also directing the beam to the surface of the sample, indicating a
      good absorption cross-section and waveguide properties. To achieve these results,
      a study of the nanocomposite optical properties as a function of the nanocrystal
      concentration is presented and the optimum conditions are found for waveguiding.

PMID- 21955573
TI  - Stem cell engraftment and survival in the ischemic heart.
AB  - Cellular therapy has emerged as a potentially novel treatment for severe ischemic
      heart disease, and there is increasing evidence that stem cell transplantation
      may improve the perfusion and contractile function of ischemic myocardium.
      However, the problem of poor donor cell engraftment and survival in ischemic
      myocardium limits the successful use of cellular therapy for treating ischemic
      heart disease. This review discusses the state-of-the-art understanding of the
      low level of cell engraftment and cell survival after transplantation into the
      ischemic heart, with a focus on the approaches that have been investigated for
      supporting and improving the survival and engraftment of transplanted cells in
      this setting.

PMID- 21955574
TI  - Open window thoracostomy and thoracoplasty to manage 90 postpneumonectomy
      empyemas.
AB  - BACKGROUND: Postpneumonectomy empyema (PPE) is a serious complication. The
      treatment options are similar to the management of any abscess, with drainage,
      ideally open, often of critical importance. After infection control, many
      techniques for space obliteration have been described. This study summarizes a 10
      year experience in the management of PPE in our center. METHODS: From 2000 to
      2010, 90 patients (83 men) with PPE were treated. Median follow-up was 5.3 years.
      Once the diagnosis of empyema was confirmed, chest drainage was performed through
      open window thoracostomy (OWT), with ensuing extramusculoperiosteal
      thoracoplasties if healthy tissue was present. RESULTS: Pneumonectomy was
      performed in 72 patients with lung cancer. Mortality after PPE was 2.2%. OWT
      achieved infection control in 89 patients. Seven OWT spontaneously healed, and 24
      were never closed. The remaining 59 patients with OWT underwent thoracoplasty.
      Mortality after thoracoplasty was 5%. Empyema recurred in 3 patients. Overall
      success rate of PPE control after pleural obliteration was 91.5%. CONCLUSIONS:
      Thoracoplasty is a reliable filling procedure. It has a significantly higher
      success rate and a lower mortality rate than the other techniques. We believe
      that this procedure has a part to play in the future management of PPE.

PMID- 21955575
TI  - Automatic detection of epileptic seizures on the intra-cranial
      electroencephalogram of rats using reservoir computing.
AB  - INTRODUCTION: In this paper we propose a technique based on reservoir computing
      (RC) to mark epileptic seizures on the intra-cranial electroencephalogram (EEG)
      of rats. RC is a recurrent neural networks training technique which has been
      shown to possess good generalization properties with limited training. MATERIALS:
      The system is evaluated on data containing two different seizure types: absence
      seizures from genetic absence epilepsy rats from Strasbourg (GAERS) and tonic
      clonic seizures from kainate-induced temporal-lobe epilepsy rats. The dataset
      consists of 452hours from 23 GAERS and 982hours from 15 kainate-induced temporal
      lobe epilepsy rats. METHODS: During the preprocessing stage, several features are
      extracted from the EEG. A feature selection algorithm selects the best features,
      which are then presented as input to the RC-based classification algorithm. To
      classify the output of this algorithm a two-threshold technique is used. This
      technique is compared with other state-of-the-art techniques. RESULTS: A balanced
      error rate (BER) of 3.7% and 3.5% was achieved on the data from GAERS and kainate
      rats, respectively. This resulted in a sensitivity of 96% and 94% and a
      specificity of 96% and 99% respectively. The state-of-the-art technique for GAERS
      achieved a BER of 4%, whereas the best technique to detect tonic-clonic seizures
      achieved a BER of 16%. CONCLUSION: Our method outperforms up-to-date techniques
      and only a few parameters need to be optimized on a limited training set. It is
      therefore suited as an automatic aid for epilepsy researchers and is able to
      eliminate the tedious manual review and annotation of EEG.

PMID- 21955576
TI  - Herd-level risk factors of bovine tuberculosis in England and Wales after the
      2001 foot-and-mouth disease epidemic.
AB  - OBJECTIVES: We present the results of a 2005 case-control study of bovine
      tuberculosis (bTB) breakdowns in English and Welsh herds. The herd management,
      farming practices, and environmental factors of 401 matched pairs of case and
      control herds were investigated to provide a picture of herd-level risk factors
      in areas of varying bTB incidence. METHODS: A global conditional logistic
      regression model, with region-specific variants, was used to compare case herds
      that had experienced a confirmed bTB breakdown to contemporaneous control herds
      matched on region, herd type, herd size, and parish testing interval. RESULTS:
      Contacts with cattle from contiguous herds and sourcing cattle from herds with a
      recent history of bTB were associated with an increased risk in both the global
      and regional analyses. Operating a farm over several premises, providing cattle
      feed inside the housing, and the presence of badgers were also identified as
      significantly associated with an increased bTB risk. CONCLUSIONS: Steps taken to
      minimize cattle contacts with neighboring herds and altering trading practices
      could have the potential to reduce the size of the bTB epidemic. In principle,
      limiting the interactions between cattle and wildlife may also be useful; however
      this study did not highlight any specific measures to implement.

PMID- 21955577
TI  - Women and Health Initiative: integrating needs and response.

PMID- 21955580
TI  - A case of parakinesia brachialis oscitans.

PMID- 21955581
TI  - Psychiatric co-morbidities and cardiovascular risk factors in people with
      lifetime history of epilepsy of an urban community.
AB  - OBJECTIVES: Depression has been consistently reported in people with epilepsy.
      Several studies also suggest a higher burden of cardiovascular diseases. We
      therefore analysed psychosocial co-morbidity and cardiovascular risk factors in
      patients with a lifetime history of epilepsy in the PsyCoLaus study, a Swiss
      urban population-based assessment of mental health and cardiovascular risk
      factors in adults aged between 35 and 66 years. PATIENTS AND METHODS: Among 3719
      participants in the PsyCoLaus study, we retrospectively identified those
      reporting at least 2 unprovoked seizures, defined as epilepsy. These subjects
      were compared to all others regarding psychiatric, social, and cardiovascular
      risk factors data using uni- and multivariable assessments. RESULTS: A
      significant higher need for social help (p<0.001) represented the only
      independent difference between 43 subjects with a history of epilepsy and 3676
      controls, while a higher prevalence of psychiatric co-morbidities (p=0.015) and a
      lower prevalent marital status (p=0.01) were only significant on univariate
      analyses. Depression and cardio-vascular risk factors, as well as educational
      level and employment, were similar among the groups. CONCLUSIONS: This analysis
      confirms an increased prevalence of psychosocial burden in subjects with a
      lifetime history of epilepsy; conversely, we did not find a higher cardiovascular
      risk. The specific urban and geographical location of our cohort and the age span
      of the studied population may account for the differences from previous studies.

PMID- 21955582
TI  - High RBM3 expression in prostate cancer independently predicts a reduced risk of
      biochemical recurrence and disease progression.
AB  - BACKGROUND: High expression of the RNA-binding protein RBM3 has previously been
      found to be associated with good prognosis in breast cancer, ovarian cancer,
      malignant melanoma and colorectal cancer. The aim of this study was to examine
      the prognostic impact of immunohistochemical RBM3 expression in prostate cancer.
      FINDINGS: Immunohistochemical RBM3 expression was examined in a tissue microarray
      with malignant and benign prostatic specimens from 88 patients treated with
      radical prostatectomy for localized disease. While rarely expressed in benign
      prostate gland epithelium, RBM3 was found to be up-regulated in prostate
      intraepithelial neoplasia and present in various fractions and intensities in
      invasive prostate cancer. High nuclear RBM3 expression was significantly
      associated with a prolonged time to biochemical recurrence (BCR) (HR 0.56, 95%
      CI: 0.34-0.93, p = 0.024) and clinical progression (HR 0.09, 95% CI: 0.01-0.71, p
      = 0.021). These associations remained significant in multivariate analysis,
      adjusted for preoperative PSA level in blood, pathological Gleason score and
      presence or absence of extracapsular extension, seminal vesicle invasion and
      positive surgical margin (HR 0.41, 95% CI: 0.19-0.89, p = 0.024 for BCR and HR
      0.06, 95% CI: 0.01-0.50, p = 0.009 for clinical progression). CONCLUSION: Our
      results demonstrate that high nuclear expression of RBM3 in prostate cancer is
      associated with a prolonged time to disease progression and, thus, a potential
      biomarker of favourable prognosis. The value of RBM3 for prognostication,
      treatment stratification and follow-up of prostate cancer patients should be
      further validated in larger studies.

PMID- 21955583
TI  - Calcium-permeable channels in plant cells.
AB  - Calcium signal transduction is a central mechanism by which plants sense and
      respond to endogenous and environmental stimuli. Cytosolic Ca(2+)  elevation is
      achieved via two cellular pathways, Ca(2+)  influx through Ca(2+)  channels in
      the plasma membrane and Ca(2+)  release from intracellular Ca(2+)  stores.
      Because of the significance of Ca(2+)  channels in cellular signaling,
      interaction with the environment and developmental processes in plants, a great
      deal of effort has been invested in recent years with regard to these important
      membrane proteins. Because of limited space, in this review we focus on recent
      findings giving insight into both the molecular identity and physiological
      function of channels that have been suggested to be responsible for the elevation
      in cytosolic Ca(2+)  level, including cyclic nucleotide gated channels, glutamate
      receptor homologs, two-pore channels and mechanosensitive Ca(2+) -permeable
      channels. We provide an overview of the regulation of these Ca(2+)  channels and
      their physiological roles and discuss remaining questions.

PMID- 21955585
TI  - Corneal hysteresis and intraocular pressure in mucopolysaccharidosis I and VI.

PMID- 21955584
TI  - Prevalence, components, and correlates of metabolic syndrome (MetS) among elderly
      Muscovites.
AB  - The goal of this study is to estimate the prevalence of MetS, together with its
      components and correlates, among elderly Russians. Our population-based sample
      included randomly selected residents of Moscow aged 55 and older: 955 women with
      an average age of 67.6, and 833 men with an average age of 68.9. MetS was defined
      according to National Cholesterol Education Program Adult Treatment Panel III
      (NCEP-ATPIII). The prevalence of MetS was found to be 41.7% in women and 26.8% in
      men. It tended to decrease with age in men, but not in women. MetS was inversely
      related to education in women, but not in men. The most prevalent individual
      components of MetS were as follows: hypertension (64.4%), abdominal obesity
      (55%), and decreased high density lipoprotein cholesterol (HDL C) (46%) for
      women; and hypertension (71%) and fasting hyperglycemia (35.2%) for men. An
      elevated level of triglycerides (TG) was the rarest MetS component, affecting
      23.5% of women and 22.1% of men. The higher female prevalence of MetS was
      attributable to abdominal obesity. MetS was found to be associated with markers
      of insulin resistance (IR), low-grade inflammation, and insufficient
      fibrinolysis. Although the metabolic burden is an important contributor to high
      levels of ill-health and cardiovascular mortality among elderly Russians
      (especially women), it does not explain why cardiovascular mortality is much
      higher in Russia than in other industrialized countries.

PMID- 21955586
TI  - Animal snoRNAs and scaRNAs with exceptional structures.
AB  - The overwhelming majority of small nucleolar RNAs (snoRNAs) fall into two clearly
      defined classes characterized by distinctive secondary structures and sequence
      motifs. A small group of diverse ncRNAs, however, shares the hallmarks of one or
      both classes of snoRNAs but differs substantially from the norm in some respects.
      Here, we compile the available information on these exceptional cases, conduct a
      thorough homology search throughout the available metazoan genomes, provide
      improved and expanded alignments, and investigate the evolutionary histories of
      these ncRNA families as well as their mutual relationships.

PMID- 21955587
TI  - Distinct activities of several RNase J proteins in methanogenic archaea.
AB  - RNA degradation plays an important role in the control of gene expression in all
      domains of life, including Archaea. While analyzing RNA degradation in different
      archaea, we faced an interesting situation. The members of a group of
      methanogenic archaea, including Methanocaldococcus jannaschii, contain neither
      the archaeal exosome nor RNase II/R homologs. However, looking for potential
      ribonucleases revealed proteins related to the recently discovered ribonuclease
      RNase J. RNase J is unique among known ribonucleases because it may combine endo-
      and 5'->3' exo-ribonucleolytic activities in a single polypeptide. Here, we
      report the characterization of the ribonuclease activities of three RNase J
      homologs encoded in the genome of the methanogenic archaeon Methanocaldococcus
      jannaschii. The analysis of the recombinant archaeal proteins purified from E.
      coli revealed an optimal activity at 60 degrees C. Whereas mjRNase J1 and -J3
      displayed exclusively 5'->3' exonucleolytic activity, mjRNase J2 is an
      endonuclease with no apparent exonuclease activity. The exonucleolytic activity
      of both mjRNase J1 and -J3 is enhanced in molecules harboring monophosphate at
      the 5' end. mjRNase J3, and to some extent mjRNase J2, degrade ssDNA. Together,
      these results reveal that in archaea lacking the exosome and RNase II/R, RNA and
      perhaps also DNA are possibly degraded by the coordinated activities of several
      RNase J proteins. Unlike bacteria, in archaea RNase J proteins provide separately
      the exo- and endonucleolytic activities that are probably essential for RNA
      degradation.

PMID- 21955588
TI  - Sleep quality in mechanically ventilated patients: comparison between NAVA and
      PSV modes.
AB  - BACKGROUND: Mechanical ventilation seems to occupy a major source in alteration
      in the quality and quantity of sleep among patients in intensive care. Quality of
      sleep is negatively affected with frequent patient-ventilator asynchronies and
      more specifically with modes of ventilation. The quality of sleep among
      ventilated patients seems to be related in part to the alteration between the
      capacities of the ventilator to meet patient demand. The objective of this study
      was to compare the impact of two modes of ventilation and patient-ventilator
      interaction on sleep architecture. METHODS: Prospective, comparative crossover
      study in 14 conscious, nonsedated, mechanically ventilated adults, during weaning
      in a university hospital medical intensive care unit. Patients were successively
      ventilated in a random ordered cross-over sequence with neurally adjusted
      ventilatory assist (NAVA) and pressure support ventilation (PSV). Sleep
      polysomnography was performed during four 4-hour periods, two with each mode in
      random order. RESULTS: The tracings of the flow, airway pressure, and electrical
      activity of the diaphragm were used to diagnose central apneas and ineffective
      efforts. The main abnormalities were a low percentage of rapid eye movement (REM)
      sleep, for a median (25th-75th percentiles) of 11.5% (range, 8-20%) of total
      sleep, and a highly fragmented sleep with 25 arousals and awakenings per hour of
      sleep. Proportions of REM sleep duration were different in the two ventilatory
      modes (4.5% (range, 3-11%) in PSV and 16.5% (range, 13-29%) during NAVA (p =
      0.001)), as well as the fragmentation index, with 40 +/- 20 arousals and
      awakenings per hour in PSV and 16 +/- 9 during NAVA (p = 0.001). There were large
      differences in ineffective efforts (24 +/- 23 per hour of sleep in PSV, and 0
      during NAVA) and episodes of central apnea (10.5 +/- 11 in PSV vs. 0 during
      NAVA). Minute ventilation was similar in both modes. CONCLUSIONS: NAVA improves
      the quality of sleep over PSV in terms of REM sleep, fragmentation index, and
      ineffective efforts in a nonsedated adult population.

PMID- 21955591
TI  - Polyacrylonitrile nanofibers prepared using coaxial electrospinning with LiCl
      solution as sheath fluid.
AB  - A modified coaxial electrospinning process including an electrolyte solution as
      sheath fluid was used for preparing high quality polymer nanofibers. A series of
      polyacrylonitrile (PAN) nanofibers were fabricated utilizing a coaxial
      electrospinning containing LiCl in N, N-dimethylacetamide (DMAc) as the sheath
      fluid. FESEM results demonstrated that the sheath LiCl solutions have a
      significant influence on the quality of PAN nanofibers. Nanofibers with smaller
      diameters, smoother surfaces and uniform structures were successfully prepared.
      The diameters of nanofibers were controlled by adjusting the conductivity of the
      sheath fluid over a suitable range and this was determined by varying LiCl
      concentrations. The influence of the effect of LiCl on the formation of PAN
      fibers is discussed and it is concluded that coaxial electrospinning with
      electrolyte solutions is a convenient and facile process for achieving high
      quality polymer nanofibers.

PMID- 21955589
TI  - Downregulation of connective tissue growth factor inhibits the growth and
      invasion of gastric cancer cells and attenuates peritoneal dissemination.
AB  - BACKGROUND: Connective tissue growth factor (CTGF) has been shown to be
      implicated in tumor development and progression. However, the role of CTGF in
      gastric cancer remains largely unknown. RESULTS: In this study, we showed that
      CTGF was highly expressed in gastric cancer tissues compared with matched normal
      gastric tissues. The CTGF expression in tumor tissue was associated with
      histologic grade, lymph node metastasis and peritoneal dissemination (P < 0.05).
      Patients with positive CTGF expression had significantly lower cumulative
      postoperative 5 year survival rate than those with negative CTGF expression
      (22.9% versus 48.1%, P < 0.001). We demonstrated that knockdown of CTGF
      expression significantly inhibited cell growth of gastric cancer cells and
      decreased cyclin D1 expression. Moreover, knockdown of CTGF expression also
      markedly reduced the migration and invasion of gastric cancer cells and decreased
      the expression of matrix metalloproteinase (MMP)-2 and MMP-9. Animal studies
      revealed that nude mice injected with the CTGF knockdown stable cell lines
      featured a smaller number of peritoneal seeding nodules than the control cell
      lines. CONCLUSIONS: These data suggest that CTGF plays an important role in cell
      growth and invasion in human gastric cancer and it appears to be a potential
      prognostic marker for patients with gastric cancer.

PMID- 21955592
TI  - Gout: current insights and future perspectives.
AB  - Gout is a relatively common inflammatory arthritis that is typically known to
      occur in middle-aged men. The prevalence of gout appears to be shifting, however,
      and is increasing in the elderly population. Gout is characterized by severely
      intense pain and can greatly impact patient quality of life. The study of gout
      and associated conditions appears to have received research attention in the
      past, however there is a resurgence in gout interest due to the abundance of
      novel evidence surrounding its diagnosis, pathophysiology, and treatment. In this
      review we describe a general overview of gout including its assessment/diagnosis,
      clinical presentations, predisposing factors, pathophysiology, abortive and
      prophylactic therapy to control gouty inflammation, and the potential future
      direction of gout treatment. PERSPECTIVE: Gout is an underappreciated and
      extremely painful condition. Over the last 2 years new thought on pathophysiology
      of gout taking into account the inflammasome and new therapeutic agents have
      changed management strategies.

PMID- 21955594
TI  - UK management practices in stage I seminoma and the Medical Research Council
      Trial of Imaging and Schedule in Seminoma Testis managed with surveillance.

PMID- 21955593
TI  - Social disparities in the use of colonoscopy by primary care physicians in
      Ontario.
AB  - BACKGROUND: It is unclear if all persons in Ontario have equal access to
      colonoscopy. This research was designed to describe long-term trends in the use
      of colonoscopy by primary care physicians (PCPs) in Ontario, and to determine
      whether PCP characteristics influence the use of colonoscopy. METHODS: We
      conducted a population-based retrospective study of PCPs in Ontario between the
      years 1996-2005. Using administrative data we identified a screen-eligible group
      of patients aged 50-74 years in Ontario. These patients were linked to the PCP
      who provided the most continuous care to them during each year. We determined the
      use of any colonoscopy among these patients. We calculated the rate of
      colonoscopy for each PCP as the number of patients undergoing colonoscopies per
      100 screen eligible patients. Negative binomial regression was used to identify
      factors associated with the rate of colonoscopy, using generalized estimating
      equations to account for clustering of patients within PCPs. RESULTS: Between
      7,955 and 8,419 PCPs in Ontario per year (median age 43 years) had at least 10
      eligible patients in their practices. The use of colonoscopy by PCPs increased
      sharply in Ontario during the study period, from a median rate of 1.51 [inter
      quartile range (IQR) 0.57-2.62] per 100 screen eligible patients in 1996 to 4.71
      (IQR 2.70-7.53) in 2005. There was substantial variation between PCPs in their
      use of colonoscopy. PCPs who were Canadian medical graduates and with more years
      of experience were more likely to use colonoscopy after adjusting for their
      patient characteristics. PCPs were more likely to use colonoscopy if their
      patient populations were predominantly women, older, had more illnesses, and if
      their patients resided in less marginalized neighborhoods (lower unemployment,
      fewer immigrants, higher income, higher education, and higher English/French
      fluency). CONCLUSIONS: There is substantial variation in the use of colonoscopy
      by PCPs, and this variation has increased as the overall use of colonoscopy
      increased over time. PCPs whose patients were more marginalized were less likely
      to use colonoscopy, suggesting that there are inequities in access.

PMID- 21955595
TI  - LINGO1 rs9652490 and rs11856808 are not associated with the risk of Parkinson's
      disease: results of a meta-analysis.

PMID- 21955596
TI  - Late withdrawal of calcineurin inhibitors and switch to mTOR inhibitors-
      beneficial or too late?

PMID- 21955597
TI  - Anion channels in plant cells.
AB  - Plant anion channels allow the efflux of anions from cells. They are involved in
      turgor pressure control, changes in membrane potential, organic acid excretion,
      tolerance to salinity and inorganic anion nutrition. The recent molecular
      identification of anion channel genes in guard cells and in roots allows a better
      understanding of their function and of the mechanisms that control their
      activation.

PMID- 21955598
TI  - [Perception in chronic illnesses: linguistic validation of the revised Illness
      Perception Questionnaire and the Brief Illness Perception Questionnaire for a
      Spanish population].
AB  - OBJECTIVE: To obtain adapted versions for the Spanish population of a specific
      version of the Revised Illness Perception Questionnaire Revised (IPQ-R(e)) and
      the Brief Illness Perception Questionnaire (BIPQ), conceptually and
      linguistically equivalent to the original questionnaires. DESIGN: Cultural
      adaptation of questionnaires: linguistic validation. SETTING: Five primary care
      centres and a tertiary hospital. PARTICIPANTS: A multidisciplinary team was
      selected. A pilot study was performed on 30 people with chronic diseases
      (hypertension, diabetes mellitus, stable ischaemic heart disease, asthma, chronic
      obstructive pulmonary disease or osteoarthritis) METHOD: The project proceeded in
      3 phases: I) Double forward-translation, II) Pilot study and III) Double back
      translation. Three consensus meetings were held, one in each phase. Another
      meeting was held with one of the authors of the original questionnaire, where we
      knew about a short version, the BIPQ. It was also included in the study. Double
      forward and back-translations were performed and consensus was reached in both
      stages. RESULTS: Phase I) The majority of IPQ-R(e) items did not raise problems
      of translation. Phase II) In the pilot study we detected that patients found some
      difficulties in connection with the comprehension and self administration of some
      items. Therefore it was decided to employ trained interviewers, to introduce
      changes in the IPQ-R(e) format and vocabulary and to adapt a specific version
      with fewer items that solved most of these difficulties Phase III) Back
      translations were very similar to the original version. The BIPQ forward and back
      translation process caused no difficulties. CONCLUSIONS: After linguistic
      validation, IPQ-R(e) and BIPQ versions conceptually and linguistically equivalent
      to original instruments were obtained.

PMID- 21955599
TI  - Specific accumulation of organotin compounds in tissues of the rock shell, Thais
      clavigera.
AB  - Concentrations of organotin compounds (butyltins and phenyltins) were determined
      in gonad, accessory sex organs, penis, digestive gland, kidney, radula with sac,
      oesophagus with crop, stomach, hypobranchial gland, rectum, mantle, osphradium,
      ctenidium, heart, salivary gland, head ganglia and muscle of imposex-exhibiting
      female and male rock shells (Thais clavigera), by gas chromatography with flame
      photometric detection (GC-FPD). Different tissue distributions were observed
      between butyltin and phenyltin compounds. More than 1000 ng TBT/g wet wt. were
      observed in ovary, digestive gland, kidney, heart, ctenidium, osphradium,
      stomach, head ganglia and penis, of both imposex-exhibiting females and males.
      More than 1000 ng TPT/g wet wt. were found in almost all tissues of both sexes.
      Approximately one-third or more of total TBT was accumulated in the digestive
      glands of both females and males, respectively. Meanwhile, approximately 40-50%
      and one-half of total TPT accumulated in the digestive glands of females and
      males, respectively.

PMID- 21955600
TI  - Excitatory projections from the amygdala to neurons in the nucleus pontis oralis
      in the rat: an intracellular study.
AB  - There is a consensus that active (REM) sleep (AS) is controlled by cholinergic
      projections from the laterodorsal and pedunculopontine tegmental nuclei (LDT/PPT)
      to neurons in the nucleus pontis oralis (NPO) that generate AS (i.e. AS-Generator
      neurons). The present study was designed to provide evidence that other
      projections to the NPO, such as those from the amygdala, are also capable of
      inducing AS. Accordingly, the responses of neurons, recorded intracellularly in
      the NPO, were examined following stimulation of the ipsilateral central nucleus
      of the amygdala (CNA) in urethane-anesthetized rats. Single pulse stimulation in
      the CNA produced an early, fast depolarizing potential (EPSP) in neurons within
      the NPO. The mean latency to the onset of these excitatory postsynaptic
      potentials (EPSPs) was 3.6+/-0.2 ms. A late, small-amplitude inhibitory synaptic
      potential (IPSP) was present following EPSPs in a portion of the NPO neurons.
      Following stimulation of the CNA with a train of 8-10 pulses, NPO neurons
      exhibited a sustained depolarization (5-10 mV) of their resting membrane
      potential. When single subthreshold intracellular depolarizing current pulses
      were delivered to NPO neurons, CNA-induced EPSPs were sufficient to promote the
      discharge of these cells. Stimulation of the CNA with a short train of stimuli
      induced potent temporal facilitation of EPSPs in NPO neurons. Two forms of
      synaptic plasticity were revealed by the patterns of response of NPO neurons
      following stimulation of the CNA: paired-pulse facilitation (PPF) and post
      tetanic potentiation (PTP). Six of recorded NPO neurons were identified
      morphologically with neurobiotin. They were medium to large, multipolar cells
      with diameters >20 MUM, which resemble AS-on cells in the NPO. The present
      results demonstrate that amygdalar projections are capable of exerting a powerful
      excitatory postsynaptic drive that activates NPO neurons. Therefore, we suggest
      that the amygdala is capable of inducing AS via direct projections to AS
      Generator neurons in the NPO.

PMID- 21955601
TI  - Progressive neurovascular disturbances in the cerebral cortex of Alzheimer's
      disease-model mice: protection by atorvastatin and pitavastatin.
AB  - Structural and functional abnormalities in the neurovascular unit (NVU) have been
      recently observed in Alzheimer's disease (AD). Statins, which are used clinically
      for reducing cholesterol levels, can also exert beneficial vascular actions.
      Thus, we examined the protective effects of statins on NVU disturbances in a
      mouse AD model. Amyloid precursor protein (APP) transgenic (Tg) mice were used as
      a model of AD. Atorvastatin (30 mg/kg/day, p.o.) or pitavastatin (3 mg/kg/day,
      p.o.) were administered from 5 to 20 months of age. Changes in the NVU, including
      the endothelium and basement membrane, as well as astrogliosis and matrix
      metalloproteinase-9 (MMP-9) activation, were assessed. There was a reduction in
      immunopositive staining for N-acetyl glucosamine oligomer (NAGO) in the
      endothelium and in collagen IV in the APP vehicle (APP/Ve) group, with collagen
      IV staining most weakest near senile plaques (SPs). There was also an increase in
      intensity and number of glial fibrillary acidic protein (GFAP)-positive
      astrocytes, particularly around the SP, where MMP-9 was more strongly labeled.
      Double immunofluorescent analysis showed that astrocytic endfeet had detached
      from the capillary endothelium in the APP/Ve group. Treatment with atorvastatin
      or pitavastatin ameliorated the activation of MMP-9. Overall, these data suggest
      that statins may have therapeutic potential for AD by protecting NVU.

PMID- 21955602
TI  - Alteration of gene expression profile in maize infected with a double-stranded
      RNA fijivirus associated with symptom development.
AB  - Maize rough dwarf disease caused by Rice black-streaked dwarf virus (RBSDV) is a
      major viral disease in China. It has been suggested that the viral infection of
      plants might cause distinct disease symptoms through the inhibition or activation
      of host gene transcription. We scanned the gene expression profile of RBSDV
      infected maize through oligomer-based microarrays to reveal possible expression
      changes associated with symptom development. Our results demonstrate that various
      resistance-related maize genes and cell wall- and development-related genes, such
      as those for cellulose synthesis, are among the genes whose expression is
      dramatically altered. These results could aid in research into new strategies to
      protect cereal crops against viruses, and reveal the molecular mechanisms of
      development of specific symptoms in rough dwarf-related diseases.

PMID- 21955603
TI  - Stromal micropapillary pattern predominant lung adenocarcinoma--a report of two
      cases.
AB  - Generally, adenocarcinomas with micropapillary pattern, featuring small papillary
      tufts lacking a central fibrovascular core, are thought to have poor prognosis.
      This pattern has been described in various organs. However, tumor cells with
      micropapillary pattern of lung adenocarcinoma are more often seen to float within
      alveolar spaces (aerogenous micropapillary pattern, AMP) than in fibrotic stroma
      like other organs (stromal micropapillary pattern, SMP) and SMP predominant lung
      adenocarcinoma (SMPPLA) has not been well described yet. We presented two cases
      of SMPPLA which were found in the last four years. Both the cases showed more
      than 50% of SMP in the tumor area. The majority of the stromal micropapillary
      clusters expressed MUC1 and epithelial membrane antigen along the outer surface
      of cell membrane. On the other hand, connective tissues surrounding stromal
      micropapillary clusters showed no reactivity for epithelial markers (thyroid
      transcription factor-1 and cytokeratin) or endothelial marker (D2-40 and CD34).
      It means clusters of SMP do not exist within air space or lymphatic or vessel
      lumens. The tumors with SMP often presented lymphatic permeation and vessel
      invasion, and intriguingly, one of the two cases showed metastasis to the
      mediastinal lymph node. Additionally, both the cases showed EGFR point mutations
      of exon 21. These results suggest that SMPPLA might be associated with poor
      prognosis and effective for EGFR tyrosine kinase inhibitors.

PMID- 21955604
TI  - Correlation of measurements from diffusion weighted MR imaging and FDG PET/CT in
      GIST patients: ADC versus SUV.
AB  - PURPOSE: We investigated the correlation relationship between ADCs measured by
      MRI and SUVs measured by PET/CT of lesions on GIST (gastrointestinal stromal
      tumor) patients to verify if MR is able to replace or serve as an alternative to
      PET/CT in GIST staging and treatment monitoring. MATERIALS AND METHODS: Between
      September 2010 and January 2011, five patients with histologically proven
      metastatic GIST in Queen Mary Hospital, Hong Kong were enrolled into our study.
      All patients underwent both MRI and PET/CT scans at prognosis. Pearson's
      correlations of twenty-nine lesions were conducted between 5 pairs of ADCs and
      SUVs values. RESULTS: Lesions in the liver, peritoneum or bowel loops were found
      by PET/CT and no extra-abdominal lesion was identified. All twenty-nine lesions
      are identifiable by MRI with sensitivity of 100%. Significant inverse correlation
      were found between ADC(mean) and SUV(mean) (P=0.006), ADC(mean) and SUV(max)
      (P=0.010), ADC(min) and SUV(max) (P=0.014), ADC(min) and SUV(mean) (P=0.026),
      rADC(min) and rSUV(max) (P=0.047). CONCLUSION: DWI is comparable to PET/CT in
      visually detecting the GIST lesions' location. Significant inverse correlations
      were found between ADCs from DWIBS and SUVs from PET/CT on data of GIST patients.
      This finding demonstrates that DWI is potentially capable of offering similar
      information for diagnosis and treatment response evaluating in GIST's patients as
      PET/CT does. Furthermore, ADC(min), which is determined by single pixel, is not
      as reliable as ADC(mean), which is weighted average value of the whole lesion
      volume.

PMID- 21955605
TI  - Factors influencing technical success and outcome of percutaneous balloon
      angioplasty in de novo native hemodialysis arteriovenous fistulas.
AB  - OBJECTIVE: To determine predictors of technical success, dysfunction recurrence
      and patency after percutaneous transluminal angioplasty (PTA) of de novo
      dysfunctional hemodialysis arteriovenous fistulas (AVFs). METHODS: Retrospective
      analysis of first time PTA of 167 AVF in 162 patients (100 men, 66+/-13 years).
      Anatomical (location, length, grade and number of stenoses) and clinical
      variables (sex, age, prior AVF, diabetes mellitus and AVF age, side and location)
      were reviewed. RESULTS: 217 stenoses or segmental occlusions were treated.
      Technical success rate (84.4%) was higher in radiocephalic AVF compared to
      brachial artery-median vein AVF (p=0.030) and was negatively correlated with
      initial stenosis (p=0.049). Dysfunction recurrence was seen in 52.7% and
      correlated negatively with technical success (p=0.013) and AVF age (p=0.008).
      Early dysfunction (within 6 months) was negatively correlated with AVF age
      (p=0.016) and positively with diabetes (p=0.003). Higher AVF age resulted in
      higher primary (p=0.005) and secondary patency rates (p=0.037-0.005).
      CONCLUSIONS: Technical success of PTA in hemodialysis AVF is affected by AVF type
      and initial stenosis and has significant effect on dysfunction recurrence, but
      not on AVF longevity. Younger AVF has increased risk for (early) recurrent
      dysfunction and lower patency rates. Patients with diabetes mellitus have higher
      risk for early dysfunction.

PMID- 21955606
TI  - Intraocular pressure changes following 20G pars-plana vitrectomy.
AB  - PURPOSE: To observe the excursions of short-term intraocular pressure (IOP) after
      20-G pars-plana vitrectomy (ppV). MATERIAL AND METHODS: In a prospective study,
      851 patients (age: mean 63 +/- 15 years) underwent unilateral ppV for various
      vitreoretinal diseases using different endotamponades [Balanced Salt Solution
      (BSS) 33.1%, Air 7.2%, SF(6) 33.6%, silicon oil 5000 cst 26.1%]. Intraocular
      pressure was measured in all patients before and at 3, 6, 24 and 48 hr after
      surgery. Survival analysis was performed to determine the cumulative hazard of
      IOP changes depending on endotamponade and time point after ppV (Log-Rang -
      Mantel Cox; p < 0.0001). RESULTS:   At baseline, IOP ranged from 0 to 50 mmHg
      (mean IOP: 15.3 +/- 5.3 mmHg). Mean IOP after surgery revealed a slight elevation
      (3 hr: 16.5 +/- 11.0 mmHg; 6 hr 16.9 +/- 9.8 mmHg; 24 hr 19.7 +/- 8.0 mmHg; 48 hr
      17.3 +/- 6.2 mmHg; range: 0-64 mmHg). Silicon oil filling revealed highest mean
      values at already 3 hr after surgery (21.8 mmHg). Also, BSS filling showed a peak
      after 3 hr; however, mean values were lower. Equivalent high IOP values as for
      silicon oil tamponade were found for gas filling; however, maximal peak was
      reached after 24 hr but not after 3 hr post-treatment. The cumulative hazard in
      all patients to reach IOP >= 30 mmHg after 24 hr was 23.9%; (IOP >= 40 mmHg =
      8.2%). Herein, oil filling revealed highest risk at all time points after
      surgery. The risk of suffering from IOP < 5 mmHg lasting longer than 6 hr was
      only 1.2% after 20 G vitrectomy. CONCLUSION: Intraocular pressure measurements
      after ppV are important to prevent unintentional high IOP, especially within the
      early phase (3 hr post-treatment) in eyes with silicon oil filling. Gas filling
      leads to prolonged IOP increase (24 hr post-treatment). Long-lasting hypotony (>=
      6 hr) is very rare after 20G vitrectomy.

PMID- 21955607
TI  - Quality of life following percutaneous mitral valve repair with the MitraClip
      System.
AB  - BACKGROUND: Percutaneous valve repair with MitraClip System is an emerging
      alternative for high surgical risk patients with severe mitral regurgitation
      (MR). QoL is a critical measure of effectiveness of this procedure. We sought to
      evaluate quality of life (QoL) and NYHA class following this novel procedure.
      METHODS: The study included 39 consecutive patients who underwent mitral valve
      repair with the MitraClip System, both for functional (64%) and degenerative
      (36%) MR. All patients received the SF-12v2 questionnaire pre-procedure and at 6
      months follow-up to assess the physical and mental health. RESULTS: Acute
      procedural success was obtained in 100%. Three patients experienced minor
      procedural complications. At follow-up 86% of patients had MR <= 1+ and 14%
      experienced a moderate MR. Mean pre-procedural SF-12v2 scores of our patients
      showed a severe impairment of perceived QoL, both for physical and mental scores;
      after six months a striking improvement in physical (PCS 35.44 vs 44.67,
      p<0.0001) and mental (MCS 38.07 vs 46.94, p<0.0001) aspect of QoL was observed.
      Furthermore, physical and mental status upgrading was higher in patients with
      functional MR. NYHA functional class improved in all patients. CONCLUSION: Our
      results show an early marked improvement in functional status and physical and
      mental health in patients underwent percutaneous mitral valve repair with the
      MitraClip System.

PMID- 21955608
TI  - Prostaglandin I2 induces apoptosis via upregulation of Fas ligand in pulmonary
      artery smooth muscle cells from patients with idiopathic pulmonary arterial
      hypertension.
AB  - BACKGROUND: Pulmonary vascular remodeling with idiopathic pulmonary arterial
      hypertension (IPAH) is associated with impaired apoptosis of pulmonary artery
      smooth muscle cells (PASMCs). We have reported that high-dose prostaglandin I2
      (PGI2) therapy markedly improved hemodynamics in IPAH patients. The therapy is
      thought to reverse vascular remodeling, though the mechanism is unclear. The aim
      of this study is to assess proapoptotic effects of PGI2 on PASMCs obtained from
      IPAH patients. METHODS: We investigated proapoptotic effects of PGI2 in PAH
      PASMCs by TUNEL assays, caspase-3,-7 assays and transmission electron microscopy.
      We examined the expression of Fas ligand (FasL), an apoptosis-inducing member of
      the TNF cytokine family, in PAH-PASMCs. We measured the serum FasL levels in IPAH
      patients treated with PGI2. RESULTS: TUNEL-positive, caspase-3, 7-active cells
      and fragmentation of the nucleus were detected in PAH-PASMCs treated with PGI2.
      The percentage of apoptotic cells induced by PGI2 at a high concentration was
      higher than that induced by PGI2 at a low concentration. PCR-array analysis
      revealed that PGI2 upregulated the FasL gene in PAH-PASMCs, and we measured the
      FasL expression by quantitative RT-PCR and Western blotting. PGI2 significantly
      increased the mRNA level of FasL by 3.98 fold and the protein level of FasL by
      1.70 fold. An IP receptor antagonist inhibited the induction of apoptosis,
      elevation of cyclic AMP and upregulation of FasL by PGI2. Serum FasL level had a
      significant positive correlation with PGI2 dose in IPAH patients treated with
      PGI2. CONCLUSIONS: PGI2 has proapoptotic effects on PAH-PASMCs via the IP
      receptor and upregulation of FasL.

PMID- 21955609
TI  - The role for cardiopulmonary exercise testing in patients with atrial septal
      defects: a review.
AB  - Secundum atrial septal defects (ASD) are the commonest congenital cardiac
      abnormality. They are often identified incidentally, or in conjunction with an
      acquired cardiac abnormality. Untreated they may lead to significant morbidity
      and mortality, with consequences including right ventricular overload and right
      heart failure, pulmonary arterial hypertension, shunt reversal and cyanosis, and
      arrhythmias. Deciding whether to close an ASD can consume as much clinical time
      as finding them or indeed closing them. In the past when surgical closure was the
      only option, the morbidity of the procedure, including the need for sternotomy or
      thoracotomy, limited its use to large defects considered likely to result in
      shunt reversal or heart failure. Smaller defects were often managed
      conservatively. However within the past 2 decades percutaneous closure has come
      to the fore and is now considered first line when morphology allows. With lower
      morbidity, this has "lowered the bar" in terms of who is considered for closure,
      although the absolute mortality risk of either procedure is low. However, even
      though mortality is low, morbidity is still significant after percutaneous
      closure. Despite this, the utilisation of ASD closure has dramatically increased
      in the last decade with a sudden rise from 2001, owing largely to growth in
      percutaneous closures. Instead of looking for symptoms, which are subjective, or
      evidence of large shunt/RV failure, an objective measure of exercise capacity
      might help identify other patients who would benefit from closure. This review
      will look at the current evidence of cardiopulmonary exercise testing (CPET) in
      ASD closure.

PMID- 21955610
TI  - Off-pump coronary artery bypass grafting in combination with transaortic
      transcatheter aortic valve implantation: a possible approach for patients with
      associated diseases.

PMID- 21955611
TI  - The interaction between fluvastatin and warfarin.

PMID- 21955612
TI  - Paclitaxel coated balloons for coronary artery interventions: a comprehensive
      review of preclinical and clinical data.
AB  - After the "mechanical era" in interventional cardiology (represented by balloon
      angioplasty and bare metal stent implantation), arrived the "local dispensing"
      era, began with the intracoronary delivery of antithrombotic or antirestenotic
      drugs. However, even drug eluting stents have some pitfalls and cannot be used in
      all clinical subsets. In this article we will review the significant data on the
      paclitaxel-coated balloons for the treatment of coronary artery disease.
      Particularly, we will review the rationale of this new treatment strategy, the
      preclinical data and will focus on available clinical studies in humans. After
      the initial boost of the paclitaxel coated balloons with the Paccocath technology
      in in-stent restenotic lesions, the experimentation of newer devices in native
      coronary arteries raised some concerns on their efficacy and safety. We will
      comment on this topic trying to understand the reasons of this failure, and will
      discuss on possible future developments and applications for these devices for
      the treatment of coronary artery disease.

PMID- 21955613
TI  - Regular exercise-induced increased number and activity of circulating endothelial
      progenitor cells attenuates age-related decline in arterial elasticity in healthy
      men.
AB  - BACKGROUND: Deficiency in number and activity of circulating EPCs is associated
      with reduced arterial elasticity in humans with advancing aging. Physical
      exercise can increase the number and activity of circulating EPCs in humans. Here
      we investigated whether regular exercise-induced enhanced circulating endothelial
      progenitor cells (EPCs) improves age-related decline in arterial elasticity in
      healthy men. METHODS: In a cross-sectional study, the number and activity of
      circulating EPCs as well as brachial-ankle pulse wave velocity (baPWV) of young
      and older sedentary or endurance-trained healthy men were studied. Then we
      observed the effect of regular exercise on circulating EPCs and baPWV of 10 older
      and 10 young sedentary healthy men. RESULTS: In both sedentary and endurance
      trained men, the number and activity of circulating EPCs were significantly low
      in older men compared with young men, which was paralleled to increased baPWV.
      After three months of regular exercise, the number and activity of circulating
      EPCs increased, and the baPWV of 10 older and 10 young sedentary healthy men
      decreased. However, the increased number and activity of circulating EPCs and
      decreased baPWV of older sedentary healthy men were higher. There was a close
      correlation between circulating EPCs and baPWV. Multivariate analysis identified
      proliferative activity of circulating EPCs as an independent predictor of baPWV.
      CONCLUSIONS: The present study demonstrates for the first time that regular
      physical exercise-induced enhanced circulating EPCs attenuates age-related
      decline in arterial elasticity in healthy men. These findings provide novel
      insights into the protective effects of exercise on age-related vascular injury.

PMID- 21955615
TI  - Chemotherapy-induced neutropenia in lung cancer patients: the role of antibiotic
      prophylaxis.
AB  - Chemotherapy-induced neutropenia can cause fatal bacterial infections. Colony
      stimulating factors (CSFs) are usually recommended as prophylaxis, while routine
      use of prophylactic antibiotics remains controversial. Based on our literature
      search in PubMed, quinolones and trimethoprim/sulfamethoxazole were the most
      frequently used prophylaxis, while CSFs were administered in 22.1% of patients.
      Lung cancer patients who received prophylactic antibiotics exhibited
      significantly fewer episodes of febrile neutropenia, fewer documented infections
      as well as shorter duration of related hospitalisations. Prophylactic use of wide
      spectrum antibiotics seems effective and should be considered as an alternative
      strategy in the prevention of chemotherapy-induced neutropenia in lung cancer
      patients.

PMID- 21955614
TI  - Differential expression of microRNA expression in tamoxifen-sensitive MCF-7
      versus tamoxifen-resistant LY2 human breast cancer cells.
AB  - Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4
      OHT) regulated in MCF-7 endocrine-sensitive versus resistant LY2 human breast
      cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells.
      Opposite expression of miRs-10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c,
      205, and 222 was confirmed. Bioinformatic analyses to impute the biological
      significance of these miRNAs identified 36 predicted gene targets from those
      regulated by 4-OHT in MCF-7 cells. Agreement in the direction of anticipated
      regulation was detected for 12 putative targets. These miRNAs with opposite
      expression between the two cell lines may be involved in endocrine resistance.

PMID- 21955616
TI  - Toxicity and delivery methods for the linamarase/linamarin/glucose oxidase
      system, when used against human glioma tumors implanted in the brain of nude
      rats.
AB  - Glioblastoma multiforme (GBM) is one of the deadliest forms of cancer, with an
      average survival time of approximately 1year despite aggressive surgery,
      radiotherapy and chemotherapy. Here, we report a preclinical study by which the
      two main energy pathways of the tumor cells, oxidative phosphorylation and
      aerobic glycolysis, are simultaneously disrupted. The therapy is based on a plant
      gene encoding a beta-glucosidase, linamarase (lis), which react with the
      substrate linamarin (lin) producing cyanide. We also use glucose oxidase (GO) to
      enhance oxidative stress and to induce cell death in the tumor. To test in vivo
      this suicide gene therapy system (lis/lin/GO), we used an orthotopic model of the
      human U87MG glioma cells, genetically modified to express the lis gene, and
      stereotactically implanted into the brains of nude rats (rnu/rnu). Despite its
      genetic condition, 6% of the animals immunorejected the xenotransplanted cells
      giving false curative results. We tried several delivery methods with limited
      success. The therapeutic cocktail, at dosages that perhaps eliminated the brain
      tumors, is too toxic for the animal causing its premature death.

PMID- 21955617
TI  - Celecoxib: considerations regarding its potential disease-modifying properties in
      osteoarthritis.
AB  - Osteoarthritis (OA) is a degenerative joint disease characterized by progressive
      loss of articular cartilage, subchondral bone sclerosis, osteophyte formation,
      and synovial inflammation, causing substantial physical disability, impaired
      quality of life, and significant health care utilization. Traditionally, non
      steroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase
      (COX)-2 inhibitors, have been used to treat pain and inflammation in OA. Besides
      its anti-inflammatory properties, evidence is accumulating that celecoxib, one of
      the selective COX-2 inhibitors, has additional disease-modifying effects.
      Celecoxib was shown to affect all structures involved in OA pathogenesis:
      cartilage, bone, and synovium. As well as COX-2 inhibition, evidence indicates
      that celecoxib also modulates COX-2-independent signal transduction pathways.
      These findings raise the question of whether celecoxib, and potentially other
      coxibs, is more than just an anti-inflammatory and analgesic drug. Can celecoxib
      be considered a disease-modifying osteoarthritic drug? In this review, these
      direct effects of celecoxib on cartilage, bone, and synoviocytes in OA treatment
      are discussed.

PMID- 21955618
TI  - EFEMP1 suppresses malignant glioma growth and exerts its action within the tumor
      extracellular compartment.
AB  - PURPOSE: There are conflicting reports regarding the function of EFEMP1 in
      different cancer types. In this study, we sought to evaluate the role of EFEMP1
      in malignant glioma biology. EXPERIMENTAL DESIGN: Real-time qRT-PCR was used to
      quantify EFEMP1 expression in 95 glioblastoma multiforme (GBM). Human high-grade
      glioma cell lines and primary cultures were engineered to express ectopic EFEMP1,
      a small hairpin RNA of EFEMP1, or treated with exogenous recombinant EFEMP1
      protein. Following treatment, growth was assayed both in vitro and in vivo
      (subcutaneous (s.c.) and intracranial (i.c.) xenograft model systems). RESULTS:
      Cox regression revealed that EFEMP1 is a favorable prognostic marker for patients
      with GBM. Over-expression of EFEMP1 eliminated tumor development and suppressed
      angiogenesis, cell proliferation, and VEGFA expression, while the converse was
      true with knock-down of endogenous EFEMP1 expression. The EFEMP1 suppression of
      tumor onset time was nearly restored by ectopic VEGFA expression; however,
      overall tumor growth rate remained suppressed. This suggested that inhibition of
      angiogenesis was only partly responsible for EFEMP1's impact on glioma
      development. In glioma cells that were treated by exogenous EFEMP1 protein or
      over-expressed endogenous EFEMP1, the EGFR level was reduced and AKT signaling
      activity attenuated. Mixing of EFEMP1 protein with cells prior to s.c. and i.c.
      implantations or injection of the protein around the established s.c. xenografts,
      both significantly suppressed tumorigenicity. CONCLUSIONS: Overall, our data
      reveals that EEFEMP1 suppresses glioma growth in vivo, both by modulating the
      tumor extracellular microenvironment and by altering critical intracellular
      oncogenic signaling pathways.

PMID- 21955619
TI  - Cell wall polysaccharides from fern leaves: evidence for a mannan-rich Type III
      cell wall in Adiantum raddianum.
AB  - Primary cell walls from plants are composites of cellulose tethered by cross
      linking glycans and embedded in a matrix of pectins. Cell wall composition varies
      between plant species, reflecting in some instances the evolutionary distance
      between them. In this work the monosaccharide compositions of isolated primary
      cell walls of nine fern species and one lycophyte were characterized and compared
      with those from Equisetum and an angiosperm dicot. The relatively high abundance
      of mannose in these plants suggests that mannans may constitute the major cross
      linking glycan in the primary walls of pteridophytes and lycophytes. Pectin
      related polysaccharides contained mostly rhamnose and uronic acids, indicating
      the presence of rhamnogalacturonan I highly substituted with galactose and
      arabinose. Structural and fine-structural analyses of the hemicellulose fraction
      of leaves of Adiantum raddianum confirmed this hypothesis. Linkage analysis
      showed that the mannan contains mostly 4-Man with very little 4,6-Man, indicating
      a low percentage of branching with galactose. Treatment of the mannan-rich
      fractions with endo-beta-mannanase produced characteristic mannan
      oligosaccharides. Minor amounts of xyloglucan and xylans were also detected.
      These data and those of others suggest that all vascular plants contain
      xyloglucans, arabinoxylans, and (gluco)mannans, but in different proportions that
      define cell wall types. Whereas xyloglucan and pectin-rich walls define Type I
      walls of dicots and many monocots, arabinoxylans and lower proportion of pectin
      define the Type II walls of commelinoid monocots. The mannan-rich primary walls
      with low pectins of many ferns and a lycopod indicate a fundamentally different
      wall type among land plants, the Type III wall.

PMID- 21955620
TI  - Changes in wheat leaf phenolome in response to cold acclimation.
AB  - A study of wheat (Triticum aestivum L.) leaves phenolome was carried out during
      cold acclimation of the winter (Claire) and spring (Bounty) varieties using a
      combination of HPLC-ESI-MS techniques. A total of 40 phenolic and flavonoid
      compounds were identified, and consisted mainly of two coumarin derivatives,
      eight simple phenolic derivatives, 10 hydroxycinnamoyl amides and 20 flavonoid
      derivatives. Identification and quantification of individual compounds were
      performed using an HPLC system coupled with a photodiode array detector and two
      different ESI-MS systems, in combination with a multiple reaction monitoring
      (MRM) technique. The analyses indicated that, although there were no qualitative
      differences in their profiles, the winter variety exhibited a higher phenolic
      content compared to the spring variety when both were grown under non-acclimated
      (control) conditions. Cold acclimation, on the other hand, resulted in a
      significant differential accumulation of phenolic compounds in both varieties:
      mostly as luteolin C-glycosides and their O-methyl derivatives in the winter
      variety (Claire) and a derivative of hydroxycinnamoyl amide in the spring variety
      (Bounty). These compounds accumulated in relatively large amounts in the
      apoplastic compartment. The accumulation of the O-methylated derivatives was
      associated with a marked increase in O-methyltransferase (OMT) activity. In
      addition, the trimethylated flavone, 3',4',5'-trimethyltricetin was identified
      for the first time in the native extracts of both control and cold-acclimated
      wheat leaves. The accumulation of a mixture of beneficial flavonoids, such as iso
      orientin, vitexin and tricin in cold acclimated wheat leaves, attests for its
      potential as an inexpensive source of a health-promoting supplement to the human
      diet.

PMID- 21955623
TI  - Roles of abscisic acid and auxin in shoot-supplied ammonium inhibition of root
      system development.
AB  - A plastic root system is a prerequisite for successful plant acclimation to
      variable environments. The normally functioning root system is the result of a
      complex interaction of root-borne signals and shoot-derived regulators. We
      recently demonstrated that AUX1, a well-studied component of auxin transport,
      mediates shoot-supplied ammonium (SSA) inhibition of lateral root (LR) formation
      in Arabidopsis. By contrast, the response did not involve ABA pathways, via which
      several other abiotic stresses affect LR formation. We proposed that SSA
      regulates LR emergence by interrupting AUX1-mediated auxin transport from shoot
      to root. Here, by analyzing both ABA- and auxin-related mutants, we show that
      AUX1 is also required for SSA-mediated suppression of primary root growth.
      Ammonium content in shoots was furthermore shown to increase linearly with shoot
      , but not root-supplied, ammonium, suggesting it may represent the internal
      trigger for SSA inhibition of root development. Taken together, our data identify
      AUX1-mediated auxin transport as a key transmission step in the sensing of
      excessive ammonium exposure and its inhibitory effect on root development. 

PMID- 21955624
TI  - Altered eosinophil proteome in a patient with hypereosinophilia from acute
      fascioliasis.
AB  - We used comparative proteomics to analyze eosinophils from a patient with
      hypereosinophilia due to fascioliasis. Using 2-dimensional electrophoresis and
      mass spectrometry, we demonstrated that the eosinophil proteome was significantly
      altered compared to those of healthy controls.

PMID- 21955625
TI  - Suppressed type 1, type 2, and type 17 cytokine responses in active tuberculosis
      in children.
AB  - Type 1 cytokine responses are known to play an important role in immunity to
      tuberculosis (TB) in children, although little is known about other factors that
      might be important. In addition, children are more prone to developing
      extrapulmonary manifestations of TB than adults. To identify the immune responses
      important both in control of infection and in extrapulmonary dissemination, we
      examined mycobacterium-specific cytokine responses of children with pulmonary TB
      (PTB) and extrapulmonary TB (ETB) and compared them with those of healthy control
      children (HC). No significant differences were found in the cytokine responses
      either with no stimulation or following mycobacterial-antigen (Ag) stimulation
      between children with PTB and ETB. On the other hand, children with active TB
      compared with HC showed markedly diminished production of type 1 (gamma
      interferon [IFN-gamma] and tumor necrosis factor alpha [TNF-alpha]), 2
      (interleukin 4 [IL-4] and IL-13), and 17 (IL-17A, IL-21, and IL-23)-associated
      cytokines with no stimulation and in response to mycobacterial antigens. This was
      not associated with significantly altered production of IL-10 or transforming
      growth factor beta (TGF-beta). Among children with ETB, those with neurologic
      involvement exhibited more significantly diminished Ag-driven IFN-gamma and IL-17
      production. Pediatric TB is characterized by diminished type 1, 2, and 17
      cytokine responses, with the most profound diminution favoring development of
      neurologic TB, suggesting a crucial role for these cytokines in protection
      against pediatric tuberculosis.

PMID- 21955626
TI  - Descemet stripping automated endothelial keratoplasty in a case with a
      posteriorly fixated iris-claw intraocular lens.
AB  - PURPOSE: To report a successful case of Descemet stripping automated endothelial
      keratoplasty (DSAEK) performed on a vitrectomized eye with a potentially unstable
      posteriorly fixated iris-claw intraocular lens (IOL). METHOD: A standard DSAEK
      procedure was performed on a 42-year-old man referred to our institution because
      of corneal edema occurring after repeat surgery for rhegmatogenous retinal
      detachment. Preoperatively, the best-corrected visual acuity was 20/200, and slit
      lamp examination revealed bullous keratopathy in the presence of a posteriorly
      fixated iris-claw IOL. RESULTS: Both surgery and the postoperative course were
      uneventful. On day 1, the graft was well centered and fully attached to the
      posterior corneal surface. The IOL was unchanged in its position. Subsequent
      follow-up showed progressive improvement in corneal clarity, with a best
      corrected visual acuity (BCVA) of 20/50 at the last follow-up examination (4
      months). CONCLUSIONS: This case demonstrates that DSAEK is an appropriate
      intervention for eyes with pseudophakic bullous keratopathy, even in the setting
      of eyes with posteriorly fixated iris-claw IOLs that are at risk of dislocation
      into the vitreous cavity.

PMID- 21955627
TI  - Treatment of ocular itching associated with ocular demodicosis by 5% tea tree oil
      ointment.
AB  - PURPOSE: To determine whether ocular itching associated with ocular demodicosis
      can be treated by lid massage with 5% tea tree oil ointment (TTOO). METHODS:
      Twenty-four patients with ocular itching and ocular Demodex were treated with
      chlortetracycline hydrochloride eye ointment lid massage for 4 weeks and then
      treatment was switched to TTOO for another 4 weeks. They were examined every 2
      weeks and their itching was graded as 0 (none), 1 (mild), 2 (moderate), or 3
      (severe). Changes of itching scores and Demodex counts were compared. RESULTS:
      Before the treatment, all 24 patients reported itching graded as 1 (n = 3), 2 (n
      = 15), and 3 (n = 6) for a period of 2 weeks to 2 years despite previous topical
      antibiotics, antiinflammatory medications, or antiallergy medications. Demodex
      counts per 8 epilated lashes were 5.5 +/- 1.6 for all patients but 4.6 +/- 1.5,
      4.8 +/- 1.9, and 7.1 +/- 2.1 for patients with grade 1, grade 2, and grade 3
      itchiness, respectively (P < 0.05 between grade 2 and grade 3). After 4 weeks of
      chlortetracycline hydrochloride eye ointment treatment, little changes were
      observed regarding itching and Demodex counts in all patients (P > 0.05). In
      contrast, after 5% TTOO treatment, 16 patients were totally free of itching and
      the remaining 8 patients had different degrees of relief (P < 0.01). The Demodex
      count decreased to 0.7 +/- 0.8 for total (P < 0.01). CONCLUSIONS: There is a
      strong correlation between ocular itching and Demodex infestation and between
      symptomatic resolution and reduction of Demodex counts by daily lid massage with
      5% TTOO.

PMID- 21955628
TI  - Incidence of early allograft rejection after Descemet membrane endothelial
      keratoplasty.
AB  - PURPOSE: To report the incidence of early allograft rejection after Descemet
      membrane endothelial keratoplasty (DMEK), that is, transplantation of isolated
      Descemet membrane with its endothelium. METHODS: The first series of 120 eyes of
      105 patients operated on for Fuchs endothelial dystrophy or pseudophakic bullous
      keratopathy, with an average 2 years of follow-up after 9.0- to 10.0-mm-diameter
      DMEK, enrolled in our study. RESULTS: During the entire study period, only 1 of
      the eyes showed any signs of a cellular immune response to the Descemet graft. A
      76-year-old patient presented with discomfort, reduced visual acuity to counting
      fingers, corneal decompensation, and a Khodadoust line in the central cornea 4
      months after (decentered) DMEK. Intensified topical corticoid therapy resulted in
      a complete visual recovery to 20/25 (0.8) within weeks. CONCLUSIONS: A "classic"
      allograft rejection (with an appearance similar to that after penetrating
      keratoplasty) can occur after DMEK. However, compared with the earlier
      (endothelial) keratoplasty procedures, DMEK may be associated with a lower
      rejection rate of <= 1%, despite transplant diameters of +/- 9.5 mm. The apparent
      immune tolerance in DMEK may result from either less "upregulation" or more
      "downregulation" of the immune system.

PMID- 21955629
TI  - Effect of subconjunctivally injected liposome-encapsulated tissue plasminogen
      activator on the absorption rate of subconjunctival hemorrhages in rabbits.
AB  - PURPOSE: To evaluate the effect of subconjunctivally injected liposome
      encapsulated tissue plasminogen activator (tPA) on the absorption rate of
      subconjunctival hemorrhages (SHs). METHODS: SHs were induced in 1 eye each of 36
      rabbits by subconjunctival injection of 0.05 mL of autologous blood. After 8
      hours, randomized subconjunctival injections were performed: 26,000 IU/mL
      liposome-encapsulated tPA (0.05 mL) in 9 eyes (group A), free-form tPA (26,000
      IU/mL; 0.05 mL) in 9 eyes (group B), only liposomes (0.05 mL) in 9 eyes (group
      C), or no injection in 9 eyes (group D). The sizes of the SHs at 8, 24, 48, 72,
      96, and 120 hours after induction were measured using an image analyzer and were
      compared among the 4 groups. RESULTS: Group A showed significantly more rapid
      absorption rates than all the other groups at 24, 48, and 72 hours and had the
      significantly shortest mean elapsed time for the complete resorption of SHs. The
      tPA activity in ocular tissue except conjunctiva and plasma were negligible
      beyond 24 hours after SH induction with both forms of tPA. In the conjunctiva,
      the tPA activity was significantly prolonged in the liposome-encapsulated tPA
      group than in the free tPA group. CONCLUSIONS: Subconjunctival injection of
      liposome-encapsulated tPA seems to enhance SH absorption in rabbits, especially
      during the early stages with minimal systemic and ocular absorption.

PMID- 21955630
TI  - Glucocorticoids suppress corneal lymphangiogenesis.
AB  - PURPOSE: To determine whether glucocorticoids suppress corneal lymphatic vessel
      growth (lymphangiogenesis) or induce lymphatic vessel regression. METHODS: We
      measured human lymphatic endothelial cell proliferation and collagen-induced
      tubulogenesis in culture conditions with and without dexamethasone, a potent
      glucocorticoid. We developed a modification of the mouse corneal suture model
      that allowed us to visualize lymphatic vessel growth (with suture) or regression
      (suture removed) using immunofluorescence and microscopic techniques. We
      administered dexamethasone or vehicle control to mice with sutured corneas. We
      visualized and quantified the corneal lymphatic vessels. We measured vascular
      endothelial growth factor-C and tumor necrosis factor-alpha messenger RNA
      expression in unsutured or sutured corneas using quantitative reverse
      transcriptase-polymerase chain reaction. RESULTS: High-dose dexamethasone did not
      change the proliferation or tubulogenesis properties of human lymphatic
      endothelial cells in vitro. We demonstrated suppressed corneal lymphatic vessel
      growth rather than lymphatic vessel regression in mice treated with
      dexamethasone. Expressions of corneal vascular endothelial growth factor-C and
      tumor necrosis factor-alpha messenger RNA were similar in mice treated with or
      without dexamethasone. CONCLUSIONS: Dexamethasone suppressed new lymphatic vessel
      growth and did not induce lymphatic vessel regression. These findings identify a
      novel mechanism of glucocorticoid action: suppression of corneal
      lymphangiogenesis.

PMID- 21955631
TI  - Intrastromal corneal ring segment implantation by femtosecond laser for the
      correction of residual astigmatism after penetrating keratoplasty.
AB  - PURPOSE: To evaluate the safety and efficacy of intracorneal ring segments
      (ICRSs) aided by femtosecond (FS) laser for the correction of residual
      astigmatism after penetrating keratoplasty (PKP). METHODS: This retrospective
      noncomparative study comprised 14 eyes of 14 patients with high astigmatism after
      PKP who had ICRS implantation by femtosecond laser. The study evaluated
      uncorrected distance visual acuity (UDVA), corrected distance visual acuity
      (CDVA), refractive astigmatism, and corneal maximum curvature. RESULTS: The CDVA
      postoperatively improved after 3 months (P < 0.001) and 6 months (P < 0.001)
      compared with CDVA preoperatively. The CDVA at 3 months was similar to that at 6
      months (P > 0.999) as well as the UDVA (P = 0.276). The preoperative astigmatism
      was higher than that after surgery (P = 0.001). The preoperative maximum
      curvature was higher than that of the postoperative maximum curvature (P <
      0.001). CONCLUSIONS: The implantation of ICRSs using the femtosecond laser for
      residual astigmatism post-PKP was safe and showed satisfactory results. It
      reduced refractive astigmatism and maximum corneal curvature and improved UDVA
      and CDVA.

PMID- 21955632
TI  - Limbal and conjunctival epithelium after corneal cross-linking using riboflavin
      and UVA.
AB  - PURPOSE: To assess possible cellular damage in the corneal and conjunctival
      epithelium after corneal cross-linking treatment. METHODS: Riboflavin-dextran
      solution was applied every 5 minutes to the right eyes of 3 rabbits 10 minutes
      before and 30 minutes during the irradiation with UVA light of 370 nm and an
      irradiance of 3 mW/cm at the 8- to 10-o'clock position, including conjunctival,
      limbal, and central corneal epithelium. In addition, 3 rabbits were treated with
      UVA light only. The rabbits were killed 24 hours later. The treated eyes were
      examined histologically using hematoxylin-eosin and periodic acid-Schiff
      staining, immunohistochemistry, and a terminal deoxynucleotidyl transferase (TdT)
      mediated deoxyuridine triphosphate-biotin nick-end labeling (TUNEL) apoptosis
      assay and compared with the left fellow eyes, which served as controls. RESULTS:
      There was no epithelial defect on fluorescein staining. No apoptosis was found in
      the corneal limbal epithelium, keratocytes, or endothelial cells in the
      irradiated area. In the adjacent conjunctival epithelium, rare superficial
      conjunctival epithelial cells were positive in TUNEL staining in all animals.
      Anti-multicytokeratin-positive staining was demonstrated in both the limbal
      corneal and the conjunctival epithelium. The proliferation marker Ki-67 was
      identified in the basal cell layer of the limbal epithelium. The frequency and
      distribution pattern of goblet cells, multicytokeratin, and the proliferation
      marker Ki-67 were the same in all eyes compared with the untreated fellow control
      eyes. CONCLUSIONS: Standard corneal cross-linking does not induce significant
      cellular epithelial damage as assessed by histological methods. Further studies
      on possible genotoxic and long-term changes would be helpful to complete the risk
      assessment.

PMID- 21955633
TI  - Retained interface gentian violet ink in Descemet stripping endothelial
      keratoplasty.
AB  - PURPOSE: To present a case of a patient who underwent right Descemet stripping
      endothelial keratoplasty (DSEK) in whom the gentian violet ink used to mark and
      orient the donor corneal graft had persisted at the host-graft interface.
      METHODS: A 57-year-old woman with progressive corneal edema from Fuchs
      endothelial dystrophy in her right eye underwent a combined
      phacoemulsification/posterior chamber intraocular lens insertion and DSEK. The
      host endothelium was stripped in a central 9.0-mm diameter. The endothelial graft
      was harvested to a depth of 400 MUm. The anterior stromal flap was lifted, and
      the stromal side of the endothelial graft was peripherally marked with a dotted
      "7" using a Codman gentian violet marker pen and a dot was placed at the center
      to aid centration. The graft was inserted and centrally positioned. The superior
      clear corneal wound was closed with 3 * 10/0 nylon interrupted sutures. The
      patient was instructed to lie face up for the first 48 hours. RESULTS: At 1 week,
      the graft was well positioned and the central gentian violet mark was not present
      but the peripheral markings were noted. At 14 months, the cornea was clear with
      an unaided visual acuity of 20/25 and best-corrected visual acuity of 20/20 but
      the superior peripheral markings persisted at the graft-host interface. Specular
      microscopy demonstrated a cell density of 1900 cells per square millimeter.
      CONCLUSIONS: Gentian violet ink marking used in DSEK operations may persist at
      the graft-host interface. Small, peripheral markings will minimize the risk of
      interference with central vision, ink-induced inflammation, and endothelial
      damage.

PMID- 21955634
TI  - Utility of real-time polymerase chain reaction in diagnosing and treating
      acanthamoeba keratitis.
AB  - PURPOSE: Using real-time polymerase chain reaction (PCR), we detected
      Acanthamoeba and monitored the changes in Acanthamoeba DNA copy number over the
      treatment course in patients suspected of Acanthamoeba keratitis (AK). METHODS:
      Subjects were 6 patients (average age, 26.2 years) suspected of AK at the Kinki
      University Outpatient Clinic. For detection of Acanthamoeba, patients' corneal
      scrapings were collected for smear analysis, culture, and real-time PCR. After
      the diagnosis of AK was confirmed, treatment was initiated based on the
      quantitative result of the real-time PCR. RESULTS: Both the smear and culture
      were positive for Acanthamoeba in 4 cases and negative in 2 cases (agreement in 3
      cases and disagreement in 2 cases). By real-time PCR, all 6 cases were positive
      for Acanthamoeba with an average DNA copy number of 4.8 +/- 9.1 * 10 copies per
      sample. We further monitored the variation in the Acanthamoeba DNA copy number
      over the treatment course and successfully treated all the patients. DNA copy
      number provided a parallel with other clinical features of AK. CONCLUSIONS: Real
      time PCR can be a useful method for a rapid and precise diagnosis of AK.
      Moreover, utility of the Acanthamoeba DNA copy number obtained by real-time PCR
      can help ophthalmologists in making the best treatment decision.

PMID- 21955635
TI  - Subconjunctival bevacizumab immediately after excision of primary pterygium: the
      first clinical trial.
AB  - PURPOSE: To investigate the effect of subconjunctival bevacizumab immediately
      after excision of primary pterygium. METHODS: Eighty patients (80 eyes) with
      primary pterygium were included in this double-blind clinical trial. The pterygia
      were excised by the bare sclera technique. Then, the patients were randomized in
      2 equal groups; group A received subconjunctival bevacizumab (1.25 mg/0.1 mL)
      injected immediately after surgical excision of the pterygium, and placebo was
      administered in the same way in group B. Patients were followed-up for 9 months
      after the operation, and the possible complications and recurrence rate were
      documented. Thirty-three patients (33 eyes) completed the study in each group.
      RESULTS: The rate of complications was comparable between the 2 groups (57.6% in
      group A versus 63.6% in group B; P = 0.61). None of these complications was
      clinically significant, and they resolved spontaneously or by using conservative
      measures. The recurrence rate was higher in group B compared with group A (57.6%
      vs. 45.5%); however, this difference was not statistically significant (P = 0.33;
      odds ratio, 1.63; 95% confidence interval, 0.62-4.31). CONCLUSIONS:
      Subconjunctival injection of bevacizumab immediately after surgical excision of
      primary pterygium is well-tolerated, but it cannot significantly prevent the
      recurrence of this condition.

PMID- 21955636
TI  - Descemetic versus pre-descemetic lamellar keratoplasty: clinical and confocal
      study.
AB  - PURPOSE: To compare the clinical findings and confocal microscopic features of
      the lamellar interface after 2 types of deep anterior lamellar keratoplasty
      (DALK): Descemetic with total stromal resection versus pre-Descemetic with deep
      stromal dissection. METHODS: Twenty eyes of 20 patients who had corneal disease
      with healthy endothelium were treated by DALK using the air technique. Baring of
      Descemet membrane (DM) was achieved for 12 eyes (Descemetic group). A fine
      stromal layer was left in 8 eyes (pre-Descemetic group). Visual acuity, interface
      clarity, corneal topography, confocal microscopy, and endothelial cell count were
      analyzed. RESULTS: DM microperforation occurred in 2 eyes (10%). No patient
      required conversion to penetrating keratoplasty (PKP) intraoperatively. Presumed
      stromal rejection occurred in 1 eye that was excluded from the study. In the
      Descemetic group, 90.9% achieved final best-corrected visual acuity (BCVA) of
      20/30 or better; in the pre-Descemetic group, 75% achieved final BCVA of 20/30 or
      better. No statistically significant difference in mean visual outcomes was found
      between groups. The reflectivity of activated keratocytes at the interface was
      less in the Descemetic than that in the pre-Descemetic group. Ten to 12 weeks
      after pre-Descemetic DALK and 4 to 6 weeks after Descemetic DALK, keratocyte
      morphology and reflectivity had returned to normal. Mean combined topographic
      astigmatism was 2.17 +/- 0.75 diopters (D) at 6 months (sutures out).
      CONCLUSIONS: The depth of the lamellar bed, smoothness, and healing process at
      the interface are the keys to optimal visual acuity. Although dissection to bare
      DM is more difficult, keratocyte activation and interface haze were less, but
      differences in final visual acuity were not significant.

PMID- 21955638
TI  - Access to harm reduction services in Atlantic Canada: implications for non-urban
      residents who inject drugs.
AB  - Awareness of drug use in rural communities and small towns has been growing, but
      we know relatively little about the challenges injection drug users (IDUs) living
      in such places face in accessing harm reduction services. Semi-structured
      interviews were conducted with 115 IDUs in urban and non-urban areas of Atlantic
      Canada. In many instances, geographic distance to a needle exchange program (NEP)
      meant that individuals living outside of urban areas and who were not provided
      services through an NEP's outreach program were at a disadvantage in terms of an
      array of supports offered through many NEPs. These include access to free clean
      injecting equipment, and such ancillary services as clothing, food, referrals,
      information and social support. The integration of the services and approaches
      provided by NEPs into mainstream health services in non-urban places is one
      possible model for improving such access.

PMID- 21955639
TI  - Activation-free printed carbon nanotube field emitters.
AB  - When a carbon nanotube paste is formulated based on highly functional
      hyperbranched polymers such as dipentaerythritol hexaacrylate, the volume
      shrinkage during thermal curing builds up internal stress that generates
      microcrack patterns on the printed surface. The nanotubes exposed in the cracks
      emit electrons successfully at such an extremely low electric field as 0.5 V um( 
      1), and reach 25.5 mA cm( - 2) of current density at 2 Vum( - 1)  from an
      optimized paste concerning mainly the size and spatial uniformity of the crack.
      In addition to the superior field emission properties with low manufacturing
      cost, this activation-free technology can provide a minimized nanohazard in the
      device fabrication process, compared to those conventional activation
      technologies developing serious nanoflakes by using destructive methods.

PMID- 21955640
TI  - Molecular detection of fluoroquinolone-resistance in multi-drug resistant
      tuberculosis in Cambodia suggests low association with XDR phenotypes.
AB  - BACKGROUND: Drug susceptibility testing (DST) remains an important concern for
      implementing treatment of MDR tuberculosis patients. Implementation of molecular
      tests for drug resistance identification would facilitate DST particularly in
      developing countries where culturing is difficult to perform. We have
      characterized multidrug resistant strains in Cambodia using MDTDRsl tests, drug
      target sequencing and phenotypic tests. METHODS: A total of 65 non-MDR and 101
      MDR TB isolates collected between May 2007 and June 2009 were tested for
      resistance to fluoroquinolones and aminoglycosides/cyclic peptides using the
      GenoType(r) MTBDRsl assay and gene sequencing. Rifampicin resistance (RMP-R) was
      tested using gene sequencing and genotyping was assessed by spoligotyping.
      RESULTS: A total of 95 of the 101 MDR strains were confirmed to be RMP-R by rpoB
      gene sequencing. Fourteen of the 101 MDR isolates (14%) carried a gyrA mutation
      associated with fluoroquinolone-resistance (FQ-R) (detected by the MTBDRsl assay
      and sequencing) compared with only 1 (1.5%) of the 65 non-MDR strains. Only 1
      (1%) of the MDR isolates was found to be XDR TB. The MDR group contained a higher
      proportion of Beijing or Beijing like strains (58%) than the non MDR group (28%).
      This percentage is higher in MDR FQ-R strains (71%). CONCLUSIONS: The new
      GenoType(r) MTBDRsl assay combined with molecular tests to detect RMP-R and
      isoniazid resistance (INH-R) represents a valuable tool for the detection of XDR
      TB. In Cambodia there is a low rate of XDR amongst MDR TB including MDR FQ-R TB.
      This suggests a low association between FQ-R and XDR TB. Strain spoligotyping
      confirms Beijing strains to be more prone to accumulate antibiotic resistance.

PMID- 21955641
TI  - [Risk factors for fragility fractures in a cohort of Spanish women].
AB  - INTRODUCTION: Fragility fractures are an important public health issue. The aim
      of this study was to analyze the association of the main osteoporotic risk
      factors related to fragility fracture in a cohort of women with an indication of
      bone densitometry (BD). METHODS: A retrospective cohort was followed-up until a
      fragile fracture occurred, in a population of women aged 40 to 90 years with a
      first visit for BD between January 1992 and February 2008. We calculated the
      incidence rate of fracture per 1000 women-years of follow-up, and the hazard
      ratio (HR) of fragile fracture using a Cox regression model. RESULTS: A total of
      49,735 women were studied. The average age of participants was 57.8 years (SD:
      8.5). Of these, 3631 women (7.1%) reported a new fragility fracture in post
      baseline visits. Risk factors with higher adjusted HR were age >= 75 years
      compared with age < 55 years (HR: 3.8; 95% CI: 3.3-4.4) and having a BC result
      evaluated as osteoporosis compared to normal (HR: 2.0; 95% CI: 1.8-2.2). A
      personal history of humerus, hip or vertebral fractures had an adjusted HR of 1.2
      (95% CI: 1.1-1.3). CONCLUSIONS: The main risk factors for fragility fracture were
      advanced age, BD result and a personal history of fracture, although 74% of
      fractures were detected with a bone mineral density classified as normal or
      osteopenia. Other relevant factors were rheumatoid arthritis or having received
      prolonged corticosteroid therapy.

PMID- 21955642
TI  - Potassium channels in plant cells.
AB  - Potassium (K(+) ) is the most abundant inorganic cation in plant cells. Unlike
      animals, plants lack sodium/potassium exchangers. Instead, plant cells have
      developed unique transport systems for K(+) accumulation and release. An
      essential role in potassium uptake and efflux is played by potassium channels.
      Since the first molecular characterization of K(+) channels from Arabidopsis
      thaliana in 1992, a large number of studies on plant potassium channels have been
      conducted. Potassium channels are considered to be one of the best characterized
      class of membrane proteins in plants. Nevertheless, knowledge on plant potassium
      channels is still incomplete. This minireview focuses on recent developments in
      the research of potassium transport in plants with a strong focus on voltage
      gated potassium channels.

PMID- 21955643
TI  - Analysis of climate paths reveals potential limitations on species range shifts.
AB  - Forecasts of species endangerment under climate change usually ignore the
      processes by which species ranges shift. By analysing the 'climate paths' that
      range shifts might follow, and two key range-shift processes--dispersal and
      population persistence--we show that short-term climatic and population
      characteristics have dramatic effects on range-shift forecasts. By employing this
      approach with 15 amphibian species in the western USA, we make unexpected
      predictions. First, inter-decadal variability in climate change can prevent range
      shifts by causing gaps in climate paths, even in the absence of geographic
      barriers. Second, the hitherto unappreciated trait of persistence during
      unfavourable climatic conditions is critical to species range shifts. Third,
      climatic fluctuations and low persistence could lead to endangerment even if the
      future potential range size is large. These considerations may render habitat
      corridors ineffectual for some species, and conservationists may need to consider
      managed relocation and augmentation of in situ populations.

PMID- 21955644
TI  - Isolation and structural elucidation of flibanserin as an adulterant in a health
      supplement used for female sexual performance enhancement.
AB  - A health supplement used for female sexual performance enhancement was sent to
      Health Sciences Authority of Singapore for testing. An unknown compound was
      detected and isolated from the health supplement and its structure was elucidated
      using LC-DAD, LC-FTMS, NMR and IR. The detected compound was identified to be
      flibanserin, a non-hormonal treatment developed for pre-menopausal woman with
      hypoactive sexual desire disorder (HSDD).

PMID- 21955645
TI  - Sports drug testing: Analytical aspects of selected cases of suspected,
      purported, and proven urine manipulation.
AB  - Manipulation of urine specimens provided by elite athletes for doping control
      purposes has been reported several times in the past, and in most of these cases
      urine substitution was eventually proven. Recent findings of suspected and
      substantiated manipulation have outlined the complexity and diversity of
      tampering options, sample appearance alterations resulting from non-manipulative
      influence, and the analytical challenges arising from these scenarios. Using
      state-of-the-art mass spectrometric and immunological doping control and forensic
      chemistry methodologies, four unusual findings were observed. One sports drug
      testing specimen was found to contain an unusually high content of saccharides
      accompanied by hordenine and Serpine-Z4, while no endogenous steroid (e.g.
      testosterone, epitestosterone, androsterone and etiocholanolone) was detected.
      This specimen was identified as non-alcoholic beer filled into the doping control
      sample container, constituting an undisputed doping offense. A doping control
      sample of bright green color was received and found to contain residues of
      methylene blue, which is not considered relevant for doping controls as no
      masking or manipulative effect is known. In addition, the number of urine samples
      of raspberry to crimson red coloration received at doping control laboratories
      has constantly increased during the last years, attributed to the presence of
      hemoglobin or betanin/isobetanin. Also here, no doping rule violation was given
      and an impact on routine analytical results was not observed. Finally, a total of
      8 sports drug testing samples collected at different competition sites was shown
      to contain identical urine specimens as indicated by steroid profile analysis and
      conclusively proven by DNA-STR (short tandem repeat) analysis. Here, the athletes
      in question were not involved in the urine substitution act but the doping
      control officer was convicted of sample manipulation.

PMID- 21955646
TI  - Dietary supplement use is associated with higher intakes of minerals from food
      sources.
AB  - BACKGROUND: Dietary supplement use is extensive in US adults. Some reports
      suggested that supplement users had higher nutrient intakes from the diet than
      did nonusers, but to our knowledge this finding has not been examined in
      nationally representative survey data. OBJECTIVE: In this analysis, we examined
      mineral intakes from the diet by supplement-use categories and how these
      supplements contributed to meeting or exceeding Dietary Reference Intakes for
      selected minerals. DESIGN: Data from adults (>=19 y of age; n = 8860) who
      participated in NHANES 2003-2006, a nationally representative, cross-sectional
      survey, were examined. Supplement use was defined as the participant's self
      reported use of a supplement that contained one or more selected minerals.
      RESULTS: Dietary intakes of minerals from food sources were higher for magnesium,
      copper, potassium, and selenium in male supplement users than in nonusers. For
      women, dietary intakes of minerals from food sources were higher for users than
      for nonusers for each mineral examined except for selenium. In women, users of
      calcium-containing dietary supplements were much more likely to meet the
      Estimated Average Requirement (EAR) than were nonusers. Even after consideration
      of supplement use, >14% of adults had inadequate intakes for calcium and
      magnesium on the basis of the percentage of adults with usual intakes less than
      the EAR. The prevalence of adults who exceeded the tolerable upper intake level
      (UL) for calcium, zinc, iron, and magnesium was higher in users than in nonusers.
      CONCLUSIONS: Individuals who used mineral-containing dietary supplements had
      higher mineral intakes from food sources in the diet than did nonusers. For all
      minerals examined, and particularly for calcium and magnesium in men and women
      and iron in women, supplement use decreased the prevalence of intake inadequacy
      for each respective mineral; however, supplements contributed to risk of
      potentially excessive intakes for calcium, iron, zinc, and magnesium.

PMID- 21955648
TI  - Physical activity, energy restriction, and the risk of pancreatic cancer: a
      prospective study in the Netherlands.
AB  - BACKGROUND: Because of their influence on insulin concentrations, we hypothesized
      that both physical activity and energy restriction may reduce the risk of
      pancreatic cancer. OBJECTIVE: We examined the associations between physical
      activity, proxies for energy restriction, and pancreatic cancer risk. DESIGN: The
      Netherlands Cohort Study consisted of 120,852 individuals who completed a
      baseline questionnaire in 1986. After 13.3 y of follow-up, 408 cases were
      available for analysis. Self-reported information on physical activity was
      collected. Three indicators were used as proxies for energy restriction: father's
      employment status during the Economic Depression (1932-1940) and place of
      residence during the World War II years (1940-1944) and the Hunger winter (1944
      1945). RESULTS: For past sports activities, we observed a significantly decreased
      risk of pancreatic cancer (HR: 0.80; 95% CI: 0.64, 0.99). Proxies for energy
      restriction were not related to pancreatic cancer risk. When the results for
      energy restriction were stratified by height, a significant multiplicative
      interaction was observed for the Economic Depression period (P = 0.002). Shorter
      individuals (height less than the sex-specific median adult height) with an
      unemployed father during the Economic Depression period had a significantly lower
      cancer risk (HR: 0.31; 95% CI: 0.14, 0.66) than did taller individuals with an
      employed father. No significant interactions were observed for exposure to energy
      restriction during the World War II years and the Hunger winter. CONCLUSIONS: Our
      results suggest a modestly decreased risk of pancreatic cancer associated with
      past sports activity. With respect to proxies for energy restriction, our
      findings suggest that shorter individuals exposed to energy restriction during
      adolescence may have a reduced risk, whereas taller individuals may not.

PMID- 21955647
TI  - Soy isoflavone phase II metabolism differs between rodents and humans:
      implications for the effect on breast cancer risk.
AB  - BACKGROUND: Human and animal studies have produced conflicting results with
      regard to the effect of soy isoflavones on breast cancer risk. This may be due to
      differences in isoflavone metabolism. OBJECTIVE: The objective of this study was
      to determine whether soy isoflavone phase II metabolism differs between humans
      and rodents. DESIGN: Circulating total and unconjugated isoflavone concentrations
      were determined by mass spectrometry in plasma samples from 7 separate studies:
      1) in Sprague-Dawley rats and in 3 strains of mice fed commercial soy-containing
      diets; 2) in Sprague-Dawley rats gavaged with genistein; 3) in healthy adults who
      consumed single servings of soy nuts, soy milk, and tempeh; 4) in healthy adults
      subchronically given soy milk; 5) in healthy women orally administered 50 mg
      genistein; 6) in healthy women orally administered 20 mg pure S-(-)equol; and 7)
      in 6-mo-old infants fed soy infant formula and later, at age 3 y, a soy germ
      isoflavone supplement. RESULTS: The proportion of unconjugated genistein in
      plasma from adults and infants who consumed different soy foods, pure genistein,
      or an isoflavone supplement was <1% in steady state and <2% at peak
      concentrations. By contrast, rodents fed soy-containing diets conjugate
      isoflavones less efficiently. The plasma percentages of unconjugated genistein
      concentrations in Sprague-Dawley rats and C57BL/6, nude, and transgenic AngptL4B6
      mice were 4.0 +/- 0.6%, 4.6 +/- 0.6%, 11.6 +/- 0%, and 30.1 +/- 4.3%,
      respectively, which represent 20, 23, 58, and 150 times that in humans.
      CONCLUSION: The markedly higher circulating concentrations of biologically active
      (unconjugated) genistein in certain strains of mice cast doubt on the value of
      the use of these rodents for gaining insight into the effects of isoflavones in
      humans, especially with regard to the effects on breast tissue.

PMID- 21955650
TI  - Effect of macronutrient intake during the second trimester on glucose metabolism
      later in pregnancy.
AB  - BACKGROUND: Dietary intake is known to influence glucose metabolism, but there is
      little consensus on the optimal distribution of macronutrient intakes during
      pregnancy to prevent gestational diabetes (GDM). OBJECTIVE: We aimed to
      investigate whether macronutrient intake distribution during the second trimester
      of pregnancy was associated with glucose metabolism later in pregnancy. DESIGN:
      Women with singleton pregnancies and without preexisting type 1 or type 2
      diabetes were included. Participants underwent a 3-h oral-glucose-tolerance test
      at 30 wk (95% CI: 25, 33 wk) gestation and were asked to recall their second
      trimester dietary intake by using a validated food-frequency questionnaire.
      RESULTS: Of the 205 participants, 47 (22.9%) had a diagnosis of GDM. A higher
      intake of saturated fat (beta +/- SEE: 0.059 +/- 0.021; P = 0.005) and trans fat
      (0.381 +/- 0.145; P = 0.009) as a percentage of energy and of added sugar (0.017
      +/- 0.007; P = 0.02) and a lower intake of vegetable and fruit fiber (-0.026 +/-
      0.012; P = 0.03) were individually associated with increased fasting glucose
      after multiple adjustment. In participants with a family history of type 2
      diabetes, a higher vegetable and fruit fiber intake was associated with reduced
      insulin resistance (-0.100 +/- 0.029; P = 0.0008) and increased insulin
      sensitivity (0.029 +/- 0.012; P = 0.01), after similar adjustment. An increased
      risk (OR per 1-SD change) of GDM was associated with lower carbohydrate (0.60;
      95% CI: 0.40, 0.90) and higher total fat (1.61; 95% CI: 1.06, 2.44) intakes as a
      percentage of energy, after similar adjustment. CONCLUSIONS: Macronutrient intake
      during the second trimester of pregnancy was associated with a risk of abnormal
      glucose metabolism later in pregnancy. This finding supports the need for
      continued work to determine optimal prenatal nutritional strategies to prevent
      GDM. This trial is registered at clinicaltrials.gov as NCT01405547.

PMID- 21955649
TI  - Fruit and vegetable intake and cognitive function in the SU.VI.MAX 2 prospective
      study.
AB  - BACKGROUND: Current hypotheses suggest that intake of fruit and vegetables (FVs)
      protects against age-related cognitive impairment. OBJECTIVE: We examined the 13
      y association between FV intake and cognitive performance in a sample of French
      adults. DESIGN: A total of 2533 subjects aged 45-60 y at baseline, who were part
      of the Supplementation with Antioxidant Vitamins and Minerals 2 (SU.VI.MAX 2)
      cohort, were selected. FV intake was estimated at baseline in participants who
      had completed at least six 24-h dietary records. Cognitive performance was
      assessed 13 y after baseline and included an evaluation of verbal memory (RI-48
      cued recall, semantic, and phonemic fluency tests) and executive function (trail
      making and forward and backward digit span tests). Principal components analysis
      was performed to account for correlations in test scores. The relation between
      cognitive performance and quartiles of FV intake was assessed by multivariate
      linear regression analyses. RESULTS: Intakes of FVs (P-trend = 0.02), fruit alone
      (P-trend = 0.04), vitamin C-rich FVs (P-trend = 0.03), vitamin C (P-trend =
      0.005), and vitamin E (P-trend = 0.04) were positively associated with verbal
      memory scores. In contrast, intakes of FVs (P-trend = 0.006), vegetables alone (P
      trend = 0.03), and beta-carotene-rich FVs (P-trend = 0.02) were negatively
      associated with executive functioning scores. CONCLUSIONS: FVs might have a
      differential effect on cognition according to groups of FVs and type of cognitive
      function. Further research using sensitive and reliable measures of various types
      of cognitive function is needed to clarify the effect of individual FV groups and
      nutrients. This trial is registered at clinicaltrials.gov as NCT00272428.

PMID- 21955651
TI  - Conjunctival findings in hyperbaric and low-tension glaucoma: an in vivo confocal
      microscopy study.
AB  - PURPOSE: To analyse the epithelial features of the bulbar conjunctiva in
      hyperbaric and low-tension glaucoma (LTG) using in vivo confocal microscopy
      (IVCM). METHODS: Thirty-six eyes of 36 patients [18 affected by primary open
      angle glaucoma (POAG) and 18 with LTG] were studied; control group was
      constituted by 28 eyes of 28 healthy subjects. All eyes were examined using
      digital confocal laser-scanning microscopy (HRT II Rostock Cornea Module). The
      main IVCM outcome measurements were mean density (MMD: cysts/mm(2)) and mean
      total area (MMA: MUm(2)) of the epithelial microcysts. RESULTS: The mean
      intraocular pressure level (mmHg +/- SD) was 15.1 +/- 1.7, 16.3 +/- 3.1 and 12.6
      +/- 1.8 in healthy, POAG and LTG eyes, respectively. Conjunctival microcysts were
      found in all patients and subjects: for healthy subjects, MMD = 10.9 +/- 11.1
      cysts/mm(2) and MMA = 1501.9 +/- 1191.1 MUm(2); for patients infected with POAG,
      MMD = 36.8 +/- 28.6 cysts/mm(2) and MMA = 7904.8 +/- 7050.5 MUm(2); and for
      patients infected with LTG MMD = 45.6 +/- 29.0 cysts/mm(2) and MMA =7946.9 +/-
      5227.5 MUm(2). MMD and MMA were not significantly different between patients
      infected with POAG and those with LTG, whereas they were significantly greater in
      patients (fourfold and fivefold, respectively) than healthy subjects.
      CONCLUSIONS: The present study demonstrated that conjunctival microcysts
      represent an in vivo feature in all eyes with medically controlled POAG and LTG.
      Therefore, conjunctiva deserves careful analysis, because its accurate
      microscopic definition could help clarify the pathophysiology of aqueous outflow
      in glaucoma.

PMID- 21955652
TI  - Importance of cumulative exposure to elevated cholesterol and blood pressure in
      development of atherosclerotic coronary artery disease in systemic lupus
      erythematosus: a prospective proof-of-concept cohort study.
AB  - INTRODUCTION: Previous studies have shown that traditional risk factors such as
      hypercholesterolemia and hypertension account for only a small proportion of the
      dramatically increased risk of atherosclerotic coronary artery disease (CAD) in
      systemic lupus erythematosus (SLE). However, in these studies, exposure to risk
      factors was measured only at baseline. In this study, our objective was to
      compare measures of cumulative exposure with remote and recent values for each of
      total cholesterol (TC), systolic (SBP), and diastolic (DBP) blood pressure in
      terms of ability to quantify risk of atherosclerotic CAD in patients with SLE.
      METHODS: Patients in the Toronto lupus cohort had TC and BP measured at each
      clinic visit and were followed up prospectively for the occurrence of CAD. For
      each patient, arithmetic mean, time-adjusted mean (AM) and area-under-the-curve
      (AUC) were calculated for serial TC, SBP, and DBP measurements. Proportional
      hazards regression models were used to compare these summary measures with recent
      and first-available ("remote") measurements in terms of ability to quantify risk
      of CAD events, defined as myocardial infarction, angina, or sudden cardiac death.
      RESULTS: The 991 patients had a mean +/- SD of 19 +/- 19 TC measurements per
      patient. Over a follow-up of 6.7 +/- 6.4 years, 86 CAD events occurred; although
      remote TC was not significantly predictive of CAD, mean and AM TC were more
      strongly predictive (hazard ratio (HR) 2.07; P = 0.003) than recent TC (HR 1.86,
      P = 0.001). AUC TC was not predictive of CAD. A similar pattern was seen for DBP
      and SBP. Older age, male sex, higher baseline and recent disease activity score,
      and corticosteroid use also increased CAD risk, whereas antimalarials were
      protective. CONCLUSIONS: In contrast to the population-based Framingham model,
      first-available TC and BP are not predictive of CAD among patients with SLE, in
      whom measures reflecting cumulative exposure over time are better able to
      quantify CAD risk. This is an important consideration in future studies of
      dynamic risk factors for CAD in a chronic relapsing-remitting disease such as
      SLE. Our findings also underpin the importance of adequate control of SLE disease
      activity while minimizing corticosteroid use, and highlight the cardioprotective
      effect of antimalarials.

PMID- 21955653
TI  - Gateway-compatible vectors for high-throughput gene functional analysis in
      switchgrass (Panicum virgatum L.) and other monocot species.
AB  - Switchgrass (Panicum virgatum L.) is a C4 perennial grass and has been identified
      as a potential bioenergy crop for cellulosic ethanol because of its rapid growth
      rate, nutrient use efficiency and widespread distribution throughout North
      America. The improvement of bioenergy feedstocks is needed to make cellulosic
      ethanol economically feasible, and genetic engineering of switchgrass is a
      promising approach towards this goal. A crucial component of creating transgenic
      switchgrass is having the capability of transforming the explants with DNA
      sequences of interest using vector constructs. However, there are limited options
      with the monocot plant vectors currently available. With this in mind, a
      versatile set of Gateway-compatible destination vectors (termed pANIC) was
      constructed to be used in monocot plants for transgenic crop improvement. The
      pANIC vectors can be used for transgene overexpression or RNAi-mediated gene
      suppression. The pANIC vector set includes vectors that can be utilized for
      particle bombardment or Agrobacterium-mediated transformation. All the vectors
      contain (i) a Gateway cassette for overexpression or silencing of the target
      sequence, (ii) a plant selection cassette and (iii) a visual reporter cassette.
      The pANIC vector set was functionally validated in switchgrass and rice and
      allows for high-throughput screening of sequences of interest in other monocot
      species as well.

PMID- 21955654
TI  - Infant feeding experiences among teen mothers in North Carolina: Findings from a
      mixed-methods study.
AB  - BACKGROUND: Adolescent mothers in the U.S. are much less likely to initiate
      breastfeeding than older mothers, and teens who do initiate breastfeeding tend to
      breastfeed for shorter durations. The purpose of this mixed-methods study is to
      investigate breastfeeding practices, barriers and facilitators among adolescent
      mothers ages 17 and younger. METHODS: Quantitative descriptive analyses are
      conducted using data from the North Carolina Pregnancy Risk Assessment Monitoring
      System (PRAMS). The population-based sample comprises 389 teens ages 13-17 giving
      birth to a live born infant in North Carolina in 2000 - 2005 and in 2007.
      Qualitative analyses are based on in-depth interviews with 22 Black, White and
      Hispanic teen mothers residing in rural and urban areas of North Carolina
      conducted between November 2007 and February 2009. RESULTS: In quantitative
      analyses, 52% (196 of 389) of North Carolina teen mothers initiated
      breastfeeding, but half of those who initiated breastfeeding (92/196) stopped
      within the first month postpartum. Hispanic teens (44/52 or 89%) were much more
      likely than Black (61/159 or 41%) or White teens (87/164 or 52%) to initiate
      breastfeeding and to continue for a longer duration. Nearly sixty two percent
      (29/52) of Hispanic respondents breastfed for greater than four weeks as compared
      to 16% (29/159) of Black respondents and 26% (39/164) of White respondents.
      Common barriers to breastfeeding initiation and continuation included not liking
      breastfeeding, returning to school, nipple pain, and insufficient milk.
      Qualitative data provided context for the quantitative findings, elucidating the
      barriers and facilitators to breastfeeding from the teens' perspective and
      insight into the ways in which breastfeeding support to teens could be enhanced.
      CONCLUSIONS: The large number of adolescents ceasing breastfeeding within the
      first month points to the need for more individualized follow-up after hospital
      discharge in the first few days postpartum, to address common technical
      challenges and to provide assistance managing the transition back to school.
      Provision of an extra home visit or outpatient visit for teens within the first
      few days following hospital discharge, and advocacy to make schools more
      compatible with breastfeeding, could potentially help teens who desire to
      breastfeed to successfully continue. These interventions warrant further research
      to test their effectiveness among adolescents.

PMID- 21955655
TI  - Removal of UV 254 nm matter and nutrients from a photobioreactor-wetland system.
AB  - The output of organic pollutants and excessive nutrients in intensive
      agricultural areas has frequently occurred, which easily lead to pollution events
      such as harmful algal blooms in downstream aquatic ecosystems. A photobioreactor
      wetland system was applied to remove UV(254 nm) matter and dissolved nutrients
      discharged from an intensive agricultural area in the Kunming region of western
      China. The photobioreactor-wetland system was composed of two main components: an
      autotrophic photobioreactor with replanted macrophytes and a constructed wetland.
      The results showed that there was a significant correlation between UV(245)(nm)
      absorbance and chemical oxygen demand (COD) concentration in the effluent of the
      agricultural ecosystem. When the hydraulic load of the photobioreactor-wetland
      system was 500 m(3)day(-1), the UV(254 nm) absorbance was dramatically reduced,
      and dissolved nutrients such as TDP, NO(3)-N and NH(4)-N were effectively
      removed. The overall average removal efficiencies were as follows in relatively
      steady-state conditions: UV(254 nm) matter (66%), TDP (71%), NO(3)-N (75%) and
      NH(4)-N (65%). Simpson's diversity index of zoobenthos indicated that the system
      could increase the zoobenthic diversity and improve the growth conditions of the
      zoobenthos habitat. The results also showed that the photobioreactor-wetland
      system could remove the UV(254 nm) matter and dissolved nutrients, providing a
      promising bio-measure for reducing the risk of pollution event occurrences in
      downstream surface waters.

PMID- 21955656
TI  - Decolorization characteristics and mechanism of Victoria Blue R removal by
      Acinetobacter calcoaceticus YC210.
AB  - Acinetobacter calcoaceticus YC210 has been isolated and its ability to remove
      Victoria Blue R (VBR) from aqueous solution was assessed. The effects of various
      factors on decolorization efficiency were investigated in a batch system. The
      decolorization efficiency was found to be optimal within a pH of 5-7 and
      increased with VBR concentration up to 450 mg/l with high efficiency (94.5%) in a
      short time. The decolorization efficiency was significantly affected by cell
      concentrations. The decolorization of VBR by A. calcoaceticus YC210 followed
      first order kinetics. The apparent kinetic parameters of the Lineweaver-Burk
      equation, R(VBR,max) and K(m), were calculated as 6.93 mg-VBR/g-cell/h and 175.8
      mg/l, respectively. Based on the biodegradation products, VBR degradation by A.
      calcoaceticus YC210 involves a stepwise demethylation process to yield partially
      dealkylated VBR species. To our knowledge, this is the first report using
      microbes to remove VBR. It clearly demonstrates the dealkylation pathway of VBR
      degradation.

PMID- 21955657
TI  - Effect of additives on Hg2+ reduction and precipitation inhibited by sodium
      dithiocarbamate in simulated flue gas desulfurization solutions.
AB  - Mercury (II) (Hg(2+)) ion can be reduced by aqueous S(IV) (sulfite and/or
      bisulfite) species, which leads to elemental mercury (Hg(0)) emissions in wet
      flue gas desulfurization (FGD) systems. Numerous reports have demonstrated the
      high trapping efficiency of sodium dithiocarbamate over heavy metals. In this
      paper, a novel sodium dithiocarbamate, DTCR, was utilized as a precipitator to
      control Hg(2+) reduction and Hg(0) emission against S(IV) in FGD solutions.
      Results indicated that Hg(2+) reduction efficiency decreased dramatically while
      precipitation rate peaked at around 91.0% in consistence with the increment of
      DTCR dosage. Initial pH and temperature had great inhibitory effects on Hg(2+)
      reduction: the Hg(2+) removal rate gradually increased and reached a plateau
      along with the increment of temperature and initial pH value. Chloride played a
      key role in Hg(2+) reduction and precipitation reactions. When Cl(-)
      concentration increased from 0 to 150 mM, Hg(2+) removal rate dropped from 93.84%
      to 86.05%, and the Hg(2+) reduction rate remained at a low level (<7.8%). SO(4)(2
      ), NO(3)(-) and other common metal ions would affect the efficiency of Hg(2+)
      reduction and precipitation reactions in the simulated desulfurization solutions:
      Hg(2+) removal rate could always be above 90%, while Hg(2+) reduction rate was
      maintained at below 10%. The predominance of DTCR over aqueous S(IV), indicated
      by the results above, has wide industrial applications in FGD systems.

PMID- 21955658
TI  - Treatment of radioactive liquid waste (Co-60) by sorption on Zeolite Na-A
      prepared from Iraqi kaolin.
AB  - Iraqi synthetic zeolite type Na-A has been suggested as ion exchange material to
      treat cobalt-60 in radioactive liquid waste which came from neutron activation
      for corrosion products. Batch experiments were conducted to find out the
      equilibrium isotherm for source sample. The equilibrium isotherm for radioactive
      cobalt in the source sample showed unfavorable type, while the equilibrium
      isotherm for the total cobalt (the radioactive and nonradioactive cobalt) in the
      source sample showed a favorable type. The ability of Na-A zeolite to remove
      cobalt from wastewater was checked for high cobalt concentration (822 mg/L) in
      addition to low cobalt concentration in the source sample (0.093 mg/L). A good
      fitting for the experimental data with Langmuir equilibrium model was observed.
      Langmuir constant qm which is related to monolayer adsorption capacity for low
      and high cobalt concentration was determined to be 0.021 and 140 mg/g(zeolite).
      The effects of important design variables on the zeolite column performance were
      studied these include initial concentration, flow rate, and bed depth. The
      experimental results have shown that high sorption capacity can be obtained at
      high influent concentration, low flow rate, and high bed depth. Higher column
      performance was obtained at higher bed depth. Thomas model was employed to
      predict the breakthrough carves for the above variables. A good fitting was
      observed with correlation coefficients between 0.915 and 0.985.

PMID- 21955659
TI  - Removal of chromium from Cr(VI) polluted wastewaters by reduction with scrap iron
      and subsequent precipitation of resulted cations.
AB  - This work presents investigations on the total removal of chromium from Cr(VI)
      aqueous solutions by reduction with scrap iron and subsequent precipitation of
      the resulted cations with NaOH. The process was detrimentally affected by a
      compactly passivation film occurred at scrap iron surface, mainly composed of
      Cr(III) and Fe(III). Maximum removal efficiency of the Cr(total) and Fe(total)
      achieved in the clarifier under circumneutral and alkaline (pH 9.1) conditions
      was 98.5% and 100%, respectively. The optimum precipitation pH range which
      resulted from this study is 7.6-8.0. Fe(total) and Cr(total) were almost entirely
      removed in the clarifier as Fe(III) and Cr(III) species; however, after Cr(VI)
      breakthrough in column effluent, chromium was partially removed in the clarifier
      also as Cr(VI), by coprecipitation with cationic species. As long the column
      effluent was free of Cr(VI), the average Cr(total) removal efficiency of the
      packed column and clarifier was 10.8% and 78.8%, respectively. Our results
      clearly indicated that Cr(VI) contaminated wastewater can be successfully treated
      by combining reduction with scrap iron and chemical precipitation with NaOH.

PMID- 21955660
TI  - Electrospun nanofibers of Bi-doped TiO2 with high photocatalytic activity under
      visible light irradiation.
AB  - Bi-doped TiO(2) nanofibers with different Bi content were firstly prepared by an
      electrospinning method. The as-prepared nanofibers were characterized by scanning
      electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron
      spectroscopy (XPS), photoluminescence spectra (PL), and UV-vis diffuse
      reflectance spectroscopy (DRS). The results indicated that Bi(3+) ions were
      successfully incorporated into TiO(2) and extended the absorption of TiO(2) into
      visible light region. The photocatalytic experiments showed that Bi-doped TiO(2)
      nanofibers exhibited higher activities than sole TiO(2) in the degradation of
      rhodamine B (RhB) and phenol under visible light irradiation (lambda>420 nm), and
      3% Bi:TiO(2) samples showed the highest photocatalytic activities.

PMID- 21955661
TI  - Synthesis and characterization of activated carbon from sawdust of Algarroba
      wood. 1. Physical activation and pyrolysis.
AB  - Synthesis of activated carbon (AC) from sawdust of Algarroba wood was performed
      as a function of the temperature under CO(2) and N(2) flow. Characterization was
      performed by adsorption-desorption N(2) isotherms, FTIR, XPS and SEM. Functional
      acid or basic groups were detected on the surface of AC. For both studied
      atmospheres, the maximum value of surface area was obtained at 800 degrees C. A
      monotonic correlation between temperature and mean pore diameter was detected
      being the higher the activation temperature the lower the mean pore width of AC.
      Ultramicroporous AC with pore diameters of 6.7 A and 5.3 A were obtained at 900
      degrees C under CO(2) and N(2) flow, respectively. It can be concluded that pore
      diameter and the functionalization of the AC surface can be controlled easily
      controlling the temperature of activation, independently of the gas atmosphere.
      The present results suggest that waste biomass is a potential source for the
      synthesis of carbon materials with potential novel applications.

PMID- 21955662
TI  - Effects of the presence of sulfonamides in the environment and their influence on
      human health.
AB  - World production and consumption of pharmaceuticals has been steadily increasing.
      Anti-infectives have been particularly important in modern therapy of microbial
      infection. Sulfonamides have been widely used for a long time as anti-infectives
      and are still widely prescribed today. This review presents the most common types
      of sulfonamides used in healthcare and veterinary medicine and discusses the
      problems connected with their presence in the biosphere. Based on the analysis of
      over 160 papers, it was found that small amounts of sulfonamides present in the
      environment were mainly derived from agricultural activities. These drugs have
      caused changes in the population of microbes that could be potentially hazardous
      to human health. This human health hazard could have a global range, and
      administrative activities have been ineffective in risk reduction.

PMID- 21955663
TI  - Dose painting by contours versus dose painting by numbers for stage II/III lung
      cancer: practical implications of using a broad or sharp brush.
AB  - PURPOSE: Local recurrence rates are high in patients with locally advanced NSCLC
      treated with 60 to 66 Gy in 2 Gy fractions. It is hypothesised that boosting
      volumes with high SUV on the pre-treatment FDG-PET scan potentially increases
      local control while maintaining acceptable toxicity levels. We compared two
      approaches: threshold-based dose painting by contours (DPBC) with voxel-based
      dose painting by numbers (DPBN). MATERIALS AND METHODS: Two dose painted plans
      were generated for 10 stage II/III NSCLC patients with 66 Gy at 2-Gy fractions to
      the entire PTV and a boost dose to the high SUV areas within the primary GTV.
      DPBC aims for a uniform boost dose at the volume encompassing the SUV 50%-region
      (GTV(boost)). DPBN aims for a linear relationship between the boost dose to a
      voxel and the underlying SUV. For both approaches the boost dose was escalated up
      to 130 Gy (in 33 fractions) or until the dose limiting constraint of an organ at
      risk was met. RESULTS: For three patients (with relatively small peripheral
      tumours) the dose within the GTV could be boosted to 130 Gy using both
      strategies. For the remaining patients the boost dose was confined by a critical
      structure (mediastinal structures in six patients, lungs in one patient). In
      general the amount of large brush DPBC boosting is limited whenever the
      GTV(boost) is close to any serial risk organ. In contrast, small brush DPBN
      inherently boosts at a voxel-by-voxel basis allowing significant higher dose
      values to high SUV voxels more distant from the organs at risk. We found that the
      biological SUV gradients are reasonably congruent with the dose gradients that
      standard linear accelerators can deliver. CONCLUSIONS: Both large brush DPBC and
      sharp brush DPBN techniques can be used to considerably boost the dose to the FDG
      avid regions. However, significantly higher boost levels can be obtained using
      sharp brush DPBN although sometimes at the cost of a less increased dose to the
      low SUV regions.

PMID- 21955664
TI  - An analytical approach to acceptance criteria for quality assurance of Intensity
      Modulated Radiotherapy.
AB  - Detectability and impact of potential treatment machine errors on IMRT treatments
      were evaluated. The ability of the gamma index to detect deliberately introduced
      errors was assessed and their clinical impact was assessed using Tumour Control
      Probability (TCP) and Normal Tissue Complication Probability. TCP was only
      marginally affected by 2mm errors in MLC position. Dose delivery errors had
      greater impact but were not detected as effectively using the gamma index.
      Acceptance criteria should include mean dose as well as gamma to help identify
      errors in the delivered dose.

PMID- 21955665
TI  - The impact of microscopic disease on the tumor control probability in non-small
      cell lung cancer.
AB  - PURPOSE: To indicate which clinical target volume (CTV) margin (if any) is needed
      for an adequate treatment of non-small-cell lung cancer (NSCLC) using either 3D
      conformal or stereotactic radiotherapy, taking the distribution of the
      microscopic disease extension (MDE) into account. METHODS AND MATERIALS: On the
      basis of the linear-quadratic biological model, a Monte-Carlo simulation was used
      to study the impact of MDE and setup deviations on the tumor control probability
      (TCP) after typical 3D conformal and stereotactic irradiation techniques. Setup
      deviations were properly accounted for in the planning target volume (PTV)
      margin. Previously measured distributions of MDE outside the macroscopic tumor in
      NSCLC patients were used. The dependence of the TCP on the CTV margins was
      quantified. RESULTS: The presence of MDE had a demonstratable influence on the
      TCP in both the 3D conformal and the stereotactic technique when no CTV margins
      were employed. The impact of MDE on the TCP values was greater in the 3D
      conformal scenario (67% TCP with MDE; 84% TCP without MDE) than for stereotactic
      radiotherapy (91% TCP with MDE; 100% TCP without MDE). Accordingly, an increase
      of the CTV margin had the greatest impact for the 3D conformal technique. Larger
      setup errors, with appropriate PTV margins, lead to an increase in TCP for both
      techniques, showing the interdependence of CTV and PTV margins. CONCLUSIONS: MDE
      may not always be eradicated by the beam penumbra or existing PTV margins using
      either 3D conformal or stereotactic radiotherapy. Nonetheless, TCP modeling
      indicates an overall local control rate above 90% for the stereotactic technique,
      while a non-zero CTV margin is recommended for better local control of MDE when
      using the 3D conformal technique.

PMID- 21955666
TI  - [Will the Radiologia journal have an impact factor at some time? Impressions of a
      radiologist].

PMID- 21955667
TI  - Antioxidant and inflammatory aspects of lipoprotein-associated phospholipase A2
      (Lp-PLA2): a review.
AB  - The association of cardiovascular events with Lp-PLA2 has been studied
      continuously today. The enzyme has been strongly associated with several
      cardiovascular risk markers and events. Its discovery was directly related to the
      hydrolysis of the platelet-activating factor and oxidized phospholipids, which
      are considered protective functions. However, the hydrolysis of bioactive lipids
      generates lysophospholipids, compounds that have a pro-inflammatory function.
      Therefore, the evaluation of the distribution of Lp-PLA2 in the lipid fractions
      emphasized the dual role of the enzyme in the inflammatory process, since the HDL
      Lp-PLA2 enzyme contributes to the reduction of atherosclerosis, while LDL-Lp-PLA2
      stimulates this process. Recently, it has been verified that diet components and
      drugs can influence the enzyme activity and concentration. Thus, the effects of
      these treatments on Lp-PLA2 may represent a new kind of prevention of
      cardiovascular disease. Therefore, the association of the enzyme with the
      traditional assessment of cardiovascular risk may help to predict more accurately
      these diseases.

PMID- 21955669
TI  - Frequency of impulse control behaviours associated with dopaminergic therapy in
      restless legs syndrome.
AB  - BACKGROUND: Low doses of dopamine agonists (DA) and levodopa are effective in the
      treatment of restless legs syndrome (RLS). A range of impulse control and
      compulsive behaviours (ICBs) have been reported following the use of DAs and
      levodopa in patients with Parkinson's disease. With this study we sought to
      assess the cross-sectional prevalence of impulse control behaviours (ICBs) in
      restless legs syndrome (RLS) and to determine factors associated with ICBs in a
      population cohort in Germany. METHODS: Several questionnaires based on validated
      and previously used instruments for assessment of ICBs were mailed out to
      patients being treated for RLS. Final diagnoses of ICBs were based on stringent
      diagnostic criteria after psychiatric interviews were performed. RESULTS: 10/140
      RLS patients of a clinical cohort (7.1%) were finally diagnosed with ICBs, 8 of
      10 on dopamine agonist (DA) therapy, 2 of 10 on levodopa. 8 of the 10 affected
      patients showed more than one type of abnormal behaviour. Among those who
      responded to the questionnaires 6/140 [4.3%] revealed binge eating, 5/140 [3.6%]
      compulsive shopping, 3/140 [2.1%] pathological gambling, 3/140 [2.1%] punding,
      and 2/140 [1.4%] hypersexuality in psychiatric assessments. Among those who did
      not respond to questionnaires, 32 were randomly selected and interviewed: only 1
      patient showed positive criteria of ICBs with compulsive shopping and binge
      eating. ICBs were associated with higher DA dose (p = 0.001), younger RLS onset
      (p = 0.04), history of experimental drug use (p = 0.002), female gender (p =
      0.04) and a family history of gambling disorders (p = 0.02), which accounted for
      52% of the risk variance. CONCLUSION: RLS patients treated with dopaminergic
      agents and dopamine agonists in particular, should be forewarned of potential
      side effects. A careful history of risk factors should be taken.

PMID- 21955670
TI  - Vibrational excitations in molecular layers probed by ballistic electron
      microscopy.
AB  - We demonstrate the information on molecular vibrational modes via the second
      derivative (d(2)I(B)/dV(2)) of the ballistic electron emission spectroscopy
      (BEES) current. The proposed method does not create huge fields as in the case of
      conventional derivative spectroscopy and maintains a zero bias across the device.
      BEES studies carried out on three different types of large polycyclic aromatic
      hydrocarbon (PAH) molecular layers show that the d(2)I(B)/dV(2)  spectra consist
      of uniformly spaced peaks corresponding to vibronic excitations. The peak spacing
      is found to be identical for molecules within the same PAH family though the BEES
      onset voltage varies for different molecules. In addition, injection into a
      particular orbital appears to correspond to a specific vibrational mode as the
      manifestation of the symmetry principle.

PMID- 21955671
TI  - Two different courses of impaired cervical kinaesthesia following a whiplash
      injury. A one-year prospective study.
AB  - A longitudinal study was conducted to observe persons with neck pain after motor
      vehicle collisions. The aims were to reveal the prospective development of
      cervical kinaesthesia and to investigate the association between the test results
      and self-reported pain and disabilities. Two different cervical kinaesthetic
      tests, the Fly test and the Head-Neck Relocation test, measured movement control
      and the relocation accuracy of the cervical spine, respectively. Self-assessment
      measures included pain intensity (VAS), neck pain and disability (NDI), fear of
      re-injury (TAMPA) and psychological distress (GHQ-28). Seventy-four subjects
      entered the study, but 47 were eligible, as they participated in all 4
      measurements at 1, 3, 6 and 12 months post-collision. According to the
      performances on the two kinaesthetic tests, the subjects could be classified into
      improvement and non-improvement groups, respectively. The result revealed, for
      the first time, two different courses of deficient cervical kinaesthesia. About
      half of the participants showed significant deteriorating performances in both
      kinaesthetic tests throughout the year (p < 0.002), while the other half improved
      their performances (p < 0.02). Generally, the relationships between the
      kinaesthetic tests and the self-assessment scores were not significant,
      irrespective of the performances on the two kinaesthetic tests. Accordingly, the
      results of the questionnaires correlated poorly or weakly with the kinaesthetic
      test results at all assessment points. The need for developing a new
      questionnaire, capturing the symptoms prevalent in patients with neck pain and
      cervical sensorimotor impairments is urgent. What determines the two different
      kinaesthetic courses need to be scrutinised in future research.

PMID- 21955672
TI  - Use of ultrasound imaging by physiotherapists: a pilot study to survey use,
      skills and training.
AB  - OBJECTIVE: This study aimed to design and pilot a questionnaire to survey the use
      of ultrasound imaging (USI) by physiotherapists in the United Kingdom (UK), the
      type and content of ultrasound training physiotherapists using USI had undertaken
      and their perceived future training needs. BACKGROUND: The use of USI by
      physiotherapists is becoming increasingly common but is highly operator dependent
      and there are safety and professional issues regarding use in physiotherapy
      practice. Currently there are no specific training guidelines relating to
      physiotherapists using USI. METHODS: A questionnaire was developed, based on
      research literature and guidelines. Twelve experts in USI commented on the
      content and design. The electronic on-line questionnaire was piloted on groups
      that were likely to be users of USI. RESULTS: Forty-six respondents completed the
      questionnaire. Results indicated that USI is used predominantly for biofeedback
      and there are many unmet training needs. Respondents reported a mismatch between
      techniques for which they had received training and those that they used in
      practice and indicated a more structured training framework is required.
      CONCLUSIONS: The development and piloting of the questionnaire provides a
      starting point for a more extensive evaluation of how USI is being used, the
      training needs of physiotherapists and benefits as a biofeedback tool. Refinement
      is needed and replication in a larger sample. Results could assist the
      development of a structured formal training framework encompassing key skills.

PMID- 21955673
TI  - The morphometric development and arterial vascularization of bovine fetal kidneys
      in the prenatal period.
AB  - This study presents a morphometric developmental analysis of bovine kidneys and a
      demonstration of intrarenal arterial vascularization in the prenatal period. A
      total of 40 Holstein bovine fetuses constituted the material of the study. The
      fetuses were divided into three groups, according to the gestational stages they
      belonged to early, mid- and late stages, such that each group comprised 10
      fetuses. Sixty kidneys and their renal arteries were evaluated using morphometric
      measurements. Furthermore, 10 bovine fetuses were injected with cast solution to
      demonstrate the intrarenal arteries. Data obtained in the present study were
      statistically analyzed. Although the right and left kidneys did not significantly
      differ from each other, significant differences existed between the different
      gestational stages (P<0.05). The kidney parameters, including length, width and
      thickness, were positively correlated with both the right and left kidneys as
      well as with gestational age. Four types of intrarenal arterial segmentation were
      demonstrated. Type I was observed in 10 kidneys (50%), type II in four kidneys
      (20%) as well as type III, and type IV in only two kidneys (10%). In the most
      frequent arterial segmentation type (type I), the renal artery divided into three
      segmental arteries, which supplied the cranial polar, medial and caudal polar
      regions of the kidney, after stemming from the abdominal aorta. Furthermore,
      cases of double and multiple renal arteries were also observed.

PMID- 21955674
TI  - Pituitary adenylatecyclase-activating polypeptide-immunoreactive nerve fibers in
      the rat epiglottis and pharynx.
AB  - The distribution of pituitary adenylatecyclase-activating polypeptide
      immunoreactive (PACAP-IR) nerve fibers was studied in the rat epiglottis and
      pharynx. PACAP-IR nerve fibers were located beneath the mucous epithelium, and
      occasionally penetrated the epithelium. These nerve fibers were abundant on the
      laryngeal side of the epiglottis and in the dorsal and lateral border region
      between naso-oral and laryngeal parts of the pharynx. PACAP-IR nerve fibers were
      also detected in taste buds within the epiglottis and pharynx. In addition, many
      PACAP-IR nerve fibers were found around acinar cells and blood vessels. The
      double immunofluorescence method demonstrated that distribution of PACAP-IR nerve
      fibers was similar to that in CGRP-IR nerve fibers in the epithelium and taste
      bud. However, distributions of PACAP-IR and CGRP-IR nerve fibers innervating
      mucous glands and blood vessels were different. The retrograde tracing method
      also demonstrated that PACAP and CGRP were co-expressed by vagal and
      glossopharyngeal sensory neurons innervating the pharynx. These findings suggest
      that PACAP-IR nerve fibers in the epithelium and taste bud of the epiglottis and
      pharynx which originate from the vagal and glossopharyngeal sensory ganglia
      include nociceptors and chemoreceptors. The origin of PACAP-IR nerve fibers which
      innervate mucous glands and blood vessels may be the autonomic ganglion.

PMID- 21955675
TI  - Letter from the editor: Our News, Policy and Profiles (NPP) section features an
      expert commentary analyzing parents' vaccination concerns.

PMID- 21955676
TI  - GeoVax expands its HIV/AIDS vaccine program.

PMID- 21955677
TI  - Parents' vaccination concerns are about more than risk and benefit.

PMID- 21955678
TI  - A passion for global vaccines.

PMID- 21955679
TI  - Novel natural product-based cinnamates and their thio and thiono analogs as
      potent inhibitors of cell adhesion molecules on human endothelial cells.
AB  - In the present study, we report the design and synthesis of novel analogs of
      cinnamates, thiocinnamates and thionocinnamates and evaluated the potencies of
      these analogs to inhibit TNF-alpha induced ICAM-1 expression on human endothelial
      cells. By using whole cell-ELISA, our screening data demonstrated that ethyl
      3',4',5'-trimethoxythionocinnamate (ETMTC) is the most potent inhibitor of TNF
      alpha induced ICAM-1, VCAM-1 and E-selectin. As functional consequences, ETMTC
      abrogated TNF-alpha induced adhesion of neutrophils to the endothelial monolayer.
      Structure-activity relationship studies revealed the critical role of the chain
      length of the alkyl group in the alcohol moiety, number of methoxy groups in the
      aromatic ring of the cinnamoyl moiety and the presence of the alpha, beta- C-C
      double bond in the thiocinnamates and thionocinnamates.

PMID- 21955680
TI  - Synthesis and comparative photodynamic properties of two isosteric alkyl
      substituted zinc(II) phthalocyanines.
AB  - The synthesis and photophysical parameters of two novel isosteric cationic
      zinc(II) phthalocyanines: 2,9(10),16(17),23(24)-tetrakis[(N-butyl-N
      methylammoniumethylsulfanyl]phthalocyaninatozinc(II) tetraiodide (6) and
      2,9(10),16(17),23(24)-tetrakis[(N-dibutyl-N
      methylammonium)ethoxy]phthalocyaninatozinc(II) tetraiodide (7) were investigated.
      Maximum absorption values were 686.5 nm and 678 nm for 6 and 7, respectively,
      whereas singlet molecular oxygen generation was 0.42 and 0.67, respectively. The
      photodynamic effect and the cellular uptake of both phthalocyanines were
      evaluated on human nasopharynx KB carcinoma cells. After light exposure,
      phthalocyanine 6 showed a higher cytotoxic activity than 7. In addition, a higher
      intracellular uptake of 6 and a preferential localization within lysosomes were
      demonstrated. The production of a greater amount of reactive oxygen species after
      phthalocyanine 6 irradiation would be responsible for its potent phototoxic
      action on KB cells.

PMID- 21955681
TI  - Diastereoselective synthesis and bioactivity of long-chain anti-2-amino-3
      alkanols.
AB  - An improved four-step approach for the stereoselective synthesis of long-chain
      anti-2-amino-3-alkanols is described. Using this method, the syntheses of
      antiproliferative (antitumoral) compounds, spisulosine (ES-285, 2), clavaminols A
      and B (3 and 4), the deacetylated products of clavaminols H and N (7 and 8), as
      well as (2S,3R)-2-aminododecan-3-ol (9) and xestoaminol C (10), have been
      achieved in excellent diastereoselectivities. In vitro study showed that these
      compounds induced cell death and dose-dependently inhibited cell proliferation in
      human glioblastoma cell line SHG-44, indicating the anti-tumor property of this
      series of compounds.

PMID- 21955682
TI  - Tree species richness promotes productivity in temperate forests through strong
      complementarity between species.
AB  - Understanding the link between biodiversity and ecosystem functioning (BEF) is
      pivotal in the context of global biodiversity loss. Yet, long-term effects have
      been explored only weakly, especially for forests, and no clear evidence has been
      found regarding the underlying mechanisms. We explore the long-term relationship
      between diversity and productivity using a forest succession model. Extensive
      simulations show that tree species richness promotes productivity in European
      temperate forests across a large climatic gradient, mostly through strong
      complementarity between species. We show that this biodiversity effect emerges
      because increasing species richness promotes higher diversity in shade tolerance
      and growth ability, which results in forests responding faster to small-scale
      mortality events. Our study generalises results from short-term experiments in
      grasslands to forest ecosystems and demonstrates that competition for light alone
      induces a positive effect of biodiversity on productivity, thus providing a new
      angle for explaining BEF relationships.

PMID- 21955683
TI  - Uniquely evolved plant ion channels.

PMID- 21955684
TI  - Biomarkers of focal and diffuse traumatic brain injury.
AB  - Traumatic brain injury (TBI) is a pathologically heterogeneous disease affecting
      people of all ages. The highest incidence of TBI occurs in young people and the
      average age is 30 to 40 years. Injury grading may range from mild with a low
      frequency (1 per 100) of life-threatening intracranial hematoma that needs
      immediate neurosurgical operation and very low mortality (1 per 1,000) to severe
      with a high likelihood of life-threatening intracranial hematoma (up to 1 per 3),
      a 40% case fatality rate and a high disability rate (2 per 3) in survivors.
      Estimation of the prognosis in severe TBI is currently based on demographic and
      clinical predictors, including age, Glasgow Coma Scale, pupillary reactions,
      extracranial injury (hypotension and hypoxia) and computed tomography indices
      (brain swelling, focal mass lesions, subarachnoid hemorrhage). Biomarkers
      reflecting damage to neurons and astrocytes may add important complementary
      information to clinical predictors of outcome and provide insight into the
      pathophysiology of TBI.

PMID- 21955685
TI  - Cisgenic barley with improved phytase activity.
AB  - The cisgenesis concept implies that plants are transformed only with their own
      genetic materials or genetic materials from closely related species capable of
      sexual hybridization. Furthermore, foreign sequences such as selection genes and
      vector-backbone sequences should be absent. We used a barley phytase gene
      (HvPAPhy_a) expressed during grain filling to evaluate the cisgenesis concept in
      barley. The marker gene elimination method was used to obtain marker-free plant
      lines. Here, the gene of interest and the selection gene are flanked by their own
      T-DNA borders to allow unlinked integration of the two genes. We analysed the
      transformants for co-transformation efficiency, increased phytase activities in
      the grain, integration of the kanamycin resistance gene of the vector-backbone
      and segregation between the HvPAPhy_a insert and the hygromycin resistance gene.
      The frequencies of the four parameters imply that it should be possible to select
      11 potentially cisgenic T(1) -lines out of the 72 T(0) -lines obtained,
      indicating that the generation of cisgenic barley is possible at reasonable
      frequencies with present methods. We selected two potential cisgenic lines with a
      single extra copy of the HvPAPhy_a insert for further analysis. Seeds from plants
      homozygous for the insert showed 2.6- and 2.8-fold increases in phytase
      activities and the activity levels were stable over the three generations
      analysed. In one of the selected lines, the flanking sequences from both the left
      and right T-DNA borders were analysed. These sequences confirmed the absence of
      truncated vector-backbone sequences linked to the borders. The described line
      should therefore be classified as cisgenic.

PMID- 21955686
TI  - Amidolytic, procoagulant, and activation-suppressing proteins produced by contact
      activation of blood factor XII in buffer solution.
AB  - The relative proportions of enzymes with amidolytic or procoagulant activity
      produced by contact activation of the blood zymogen factor XII (FXII, Hageman
      factor) in buffer solution depends on activator surface chemistry/energy. As a
      consequence, chromogenic assay of amidolytic activity (cleavage of amino acid
      bonds in s-2302 chromogen) does not correlate with the traditional plasma
      coagulation time assay for procoagulant activity (protease activity inducing
      clotting of blood plasma). Amidolytic activity did not vary significantly with
      activator particle surface energy, herein measured as water adhesion tension
      tau(o)=gamma(lv)(o)costheta(a) ; where gamma(lv)(o) is pure buffer interfacial
      tension and theta(a) is the advancing contact angle. By contrast, procoagulant
      activity varied as a parabolic-like function of tau(o), high at both hydrophobic
      and hydrophilic extremes of activator surface energy and falling through a broad
      minimum within a 20<tau(o)<40 mJ/m(2) (55 degrees <theta(a) < 75 degrees ) range,
      corroborating and expanding previously-published work. It is inferred from these
      functional assays that an unknown number of protein fragments are produced by
      contact activation of FXII (a.k.a. autoactivation) rather than just alphaFXIIa
      and betaFXIIa as popularly believed. Autoactivation products produced by
      activator particles within the 20<tau(o)<40 mJ/m(2) (55 degrees <theta(a) < 75
      degrees ) surface-energy range suppresses production of procoagulant enzymes by
      activators selected from the hydrophobic or hydrophilic surface-energy extremes
      through as-yet unknown biophysical chemistry. Suppression proteins may be
      responsible for the experimentally-observed autoinhibition of the autoactivation
      reaction.

PMID- 21955687
TI  - Synergistic regulation of cell function by matrix rigidity and adhesive pattern.
AB  - Cell-extracellular matrix (ECM) interactions play a critical role in regulating
      cellular behaviors. Recent studies of cell-ECM interactions have mainly focused
      on the actomyosin based and adhesion mediated mechanosensing pathways to
      understand how individual mechanical signals in the cell microenvironment, such
      as matrix rigidity and adhesive ECM pattern, are sensed by the cell and further
      trigger downstream intracellular signaling cascades and cellular responses.
      However, synergistic and collective regulation of cellular behaviors by matrix
      rigidity and adhesive ECM pattern are still elusive and largely uncharacterized.
      Here, we generated a library of microfabricated polydimethylsiloxane (PDMS)
      micropost arrays to study the synergistic and independent effects of matrix
      rigidity and adhesive ECM pattern on mechanoresponsive behaviors of both NIH/3T3
      fibroblasts and human umbilical vein endothelial cells (HUVECs). We showed that
      both cell types were mechanosensitive and their cell spreading, FA formation,
      cytoskeletal contractility, and proliferation were all strongly dependent on both
      substrate rigidity and adhesive ECM pattern. We further showed that under the
      same substrate rigidity condition, smaller and closer adhesive ECM islands would
      cause both cells to spread out more, form more adhesion structures, and have a
      higher proliferation rate. The influence of adhesive ECM pattern on rigidity
      mediated cytoskeletal contractility was cell type specific and was only
      significant for NIH/3T3. Morphometric analysis of cell populations revealed a
      strong correlation between focal adhesion and cell spreading, regardless of
      substrate rigidity and adhesive ECM pattern. We also observed a strong
      correlation between cellular traction force and cell spreading, with a
      substantially smaller independent effect of substrate rigidity on traction force.
      Our study here had determined key aspects of the biomechanical responses of
      adherent cells to independent and collective changes of substrate rigidity and
      adhesive ECM pattern.

PMID- 21955688
TI  - A prospective, randomised, controlled trial using a Mg-hydroxyapatite -
      demineralized bone matrix nanocomposite in tibial osteotomy.
AB  - We in vivo investigated the bone healing ability of a nanocomposite (DBSint(r)),
      constituted by biomimetic nano-structured Mg-hydroxyapatite (SINTlife(r)) and
      human demineralized bone matrix. Thirty-one subjects undergoing high tibial
      osteotomy for genu varus were randomly assigned to three groups: during surgery,
      DBSint(r) was inserted into nine patients, SINTlife(r) in thirteen patients and
      lyophilised bone chips, that is the routine surgery, in nine subjects. As outcome
      measures, clinical, radiographic and histomorphometry scores were calculated. The
      osseointegration was evaluated by imaging six weeks, three, six and twelve months
      after surgery. At six-week follow-up, DBSint(r) showed a significantly higher
      osseointegration rate in comparison with lyophilised bone chips (p = 0.008). At
      the same follow-up, CT-guided bone biopsies were obtained and analysed by
      histomorphometry: a good osteogenetic potential was demonstrated with DBSint(r),
      as well as with SINTlife(r) and controls. Unresorbed material was evident with
      DBSint(r) and SINTlife(r), with a significantly higher percentage in SINTlife(r)
      group. At 1-year follow-up, DBSint(r) was demonstrated as effective and safe as
      SINTlife(r) and lyophilized bone chips. More significant results could be
      obtained by continuing the clinical trial, by increasing the patient number and
      the study power. Eventually, the role of non-resorbed graft remnants is still
      unclear and requires further investigation.

PMID- 21955689
TI  - The use of molecular fluorescent markers to monitor absorption and distribution
      of xenobiotics in a silkworm model.
AB  - The fate of xenobiotics in living organisms is determined by their in vivo
      absorption, distribution, metabolism and excretion. A convenient and scalable
      animal model of these biological processes is thus highly beneficial in
      understanding the effects of xenobiotics. Here we present a silkworm model to
      investigate the molecular properties-directed absorption, distribution and
      excretion of fluorescent compounds as model xenobiotics through introducing the
      compounds into the silkworm's diet and monitoring the resulting color and
      fluorescence in the silkworm's body. The efficient uptake of xenobiotics into
      silk has been further studied through quantitative analysis of the intrinsically
      colored and highly luminescent silk secreted by silkworm. Our findings provide
      first-hand insights to better understand the molecular properties that allow
      specific materials to be incorporated into silk while it is being produced in the
      silk gland. The use of resulting luminescent silk as scaffold for tissue
      engineering application has been demonstrated to clearly reveal the interaction
      of silk with cells. Furthermore, this new development also paves a way to produce
      various functional silk embedded with stimuli-sensitive dyes or drugs as novel
      biomaterials for in vivo applications.

PMID- 21955690
TI  - 3D cell entrapment in crosslinked thiolated gelatin-poly(ethylene glycol)
      diacrylate hydrogels.
AB  - The combined use of natural ECM components and synthetic materials offers an
      attractive alternative to fabricate hydrogel-based tissue engineering scaffolds
      to study cell-matrix interactions in three-dimensions (3D). A facile method was
      developed to modify gelatin with cysteine via a bifunctional PEG linker, thus
      introducing free thiol groups to gelatin chains. A covalently crosslinked gelatin
      hydrogel was fabricated using thiolated gelatin and poly(ethylene glycol)
      diacrylate (PEGdA) via thiol-ene reaction. Unmodified gelatin was physically
      incorporated in a PEGdA-only matrix for comparison. We sought to understand the
      effect of crosslinking modality on hydrogel physicochemical properties and the
      impact on 3D cell entrapment. Compared to physically incorporated gelatin
      hydrogels, covalently crosslinked gelatin hydrogels displayed higher maximum
      weight swelling ratio (Q(max)), higher water content, significantly lower
      cumulative gelatin dissolution up to 7 days, and lower gel stiffness.
      Furthermore, fibroblasts encapsulated within covalently crosslinked gelatin
      hydrogels showed extensive cytoplasmic spreading and the formation of cellular
      networks over 28 days. In contrast, fibroblasts encapsulated in the physically
      incorporated gelatin hydrogels remained spheroidal. Hence, crosslinking ECM
      protein with synthetic matrix creates a stable scaffold with tunable mechanical
      properties and with long-term cell anchorage points, thus supporting cell
      attachment and growth in the 3D environment.

PMID- 21955691
TI  - Slow conduction and gap junction remodeling in murine ventricle after chronic
      alcohol ingestion.
AB  - BACKGROUND: Long-term heavy alcohol drinkers are prone to the development of
      cardiac arrhythmia. To understand the mechanisms, we evaluated the cardiac
      structural and electrophysiological changes in mice chronically drinking
      excessive alcohol. RESULTS: Male C57BL/6J mice were given 36% alcohol in the
      drinking water. Those given blank water were used as control. Twelve weeks later,
      the phenotypic characteristics of the heart, including gap junctions and
      electrical properties were examined. In the alcohol group the ventricles
      contained a smaller size of cardiomyocytes and a higher density of capillary
      networks, compared to the control. Western blots showed that, after drinking
      alcohol, the content of connexin43 (Cx43) protein in the left ventricle was
      increased by 18% (p < 0.05). Consistently, immunoconfocal microscopy demonstrated
      that Cx43 gap junctions were up-regulated in the alcohol group with a
      disorganized distribution, compared to the control. Optical mapping showed that
      the alcohol group had a reduced conduction velocity (40 +/- 18 vs 60 +/- 7
      cm/sec, p < 0.05) and a higher incidence of ventricular tachyarrhythmia (62% vs
      30%, p < 0.05). CONCLUSION: Long-term excessive alcohol intake resulted in
      extensive cardiac remodeling, including changes in expression and distribution of
      gap junctions, growth of capillary network, reduction of cardiomyocyte size, and
      decrease of myocardial conduction.

PMID- 21955693
TI  - Thrombotic gene polymorphisms and postoperative outcome after coronary artery
      bypass graft surgery.
AB  - BACKGROUND: Emerging perioperative genomics may influence the direction of risk
      assessment and surgical strategies in cardiac surgery. The aim of this study was
      to investigate whether single nucleotide polymorphisms (SNP) affect the clinical
      presentation and predispose to increased risk for postoperative adverse events in
      patients undergoing coronary artery bypass grafting surgery (CABG). METHODS: A
      total of 220 patients undergoing first-time CABG between January 2005 and May
      2008 were screened for factor V gene G1691A (FVL), prothrombin/factor II G20210A
      (PT G20210A), angiotensin I-converting enzyme insertion/deletion (ACE-ins/del)
      polymorphisms by PCR and Real Time PCR. End points were defined as death,
      myocardial infarction, stroke, postoperative bleeding, respiratory and renal
      insufficiency and event-free survival. Patients were compared to assess for any
      independent association between genotypes for thrombosis and postoperative
      phenotypes. RESULTS: Among 220 patients, the prevalence of the heterozygous FVL
      mutation was 10.9% (n = 24), and 3.6% (n = 8) were heterozygous carriers of the
      PT G20210A mutation. Genotype distribution of ACE-ins/del was 16.6%, 51.9%, and
      31.5% in genotypes I/I, I/D, and D/D, respectively. FVL and PT G20210A mutations
      were associated with higher prevalence of totally occluded coronary arteries (p <
      0.001). Furthermore the risk of left ventricular aneurysm formation was
      significantly higher in FVL heterozygote group compared to FVL G1691G (p =
      0.002). ACE D/D genotype was associated with hypertension (p = 0.004), peripheral
      vascular disease (p = 0.006), and previous myocardial infarction (p = 0.007).
      CONCLUSIONS: FVL and PT G20210A genotypes had a higher prevalence of totally
      occluded vessels potentially as a result of atherothrombotic events. However,
      none of the genotypes investigated were independently associated with mortality.

PMID- 21955694
TI  - A case of penetrating axillary trauma.
AB  - INTRODUCTION: Deep penetrating traumas of the axilla extending to the neck are
      rare and potentially dangerous. OBSERVATION: An 11-year-old child presented with
      an impressive penetrating axillary injury extending to the neck after falling on
      a tree branch. The wound was explored in the operating room (OR). A fragment of
      the branch was removed without injuring any vascular structure. The only lesion
      concerned the hypopharynx. DISCUSSION: Cervical wounds may have an axillary
      origin. These wounds must be systematically explored in the OR, given the risk of
      upper airway obstruction and vascular lesion.

PMID- 21955695
TI  - Postprandial lipemia and cardiovascular disease risk: Interrelationships between
      dietary, physiological and genetic determinants.
AB  - Although the independence of the association and causality has not been fully
      established, non-fasting (postprandial) triglyceride (TG) concentrations have
      emerged as a clinically significant cardiovascular disease (CVD) risk factor. In
      the current review, findings from three insightful prospective studies in the
      area, namely the Women's Health Study, the Copenhagen City Heart Study and the
      Norwegian Counties Study, are discussed. An overview is provided as to the likely
      etiological basis for the association between postprandial TG and CVD, with a
      focus on both lipid and non-lipid (inflammation, hemostasis and vascular
      function) risk factors. The impact of various lifestyle and physiological
      determinants are considered, in particular genetic variation and meal fat
      composition. Furthermore, although data is limited some information is provided
      as to the relative and interactive impact of a number of modulators of lipemia.
      It is evident that relative to age, gender and body mass index (known modulators
      of postprandial lipemia), the contribution of identified gene variants to the
      heterogeneity observed in the postprandial response is likely to be relatively
      small. Finally, we highlight the need for the development of a standardised 'fat
      tolerance test' for use in clinical trials, to allow the integration and
      comparison of data from individual studies.

PMID- 21955696
TI  - Histology of adipose tissue inflammation in Dercum's disease, obesity and normal
      weight controls: a case control study.
AB  - BACKGROUND: Dercum's disease (DD) is characterised by obesity and chronic pain (>
      3 months) in the adipose tissue. The pathogenesis of DD is unknown, but
      inflammatory components have been proposed. In previous reports and studies, an
      inconsistent picture of the histological appearance of the adipose tissue in DD
      has been described. The aim of this investigation was to examine the histological
      appearance of adipose tissue in patients with DD, with particular focus on
      inflammatory signs. METHODS: Fat biopsies were sampled from painful regions from
      53 patients with DD. In 28 of the patients, a control adipose tissue biopsy was
      taken from a location where the patient did not experience any pain. In addition,
      fat biopsies were sampled from 41 healthy pain-free obese control patients and 11
      healthy pain-free normal weight control patients. The extent of inflammation was
      evaluated on histological sections stained with haematoxylin-eosin. RESULTS:
      There was no statistically significant difference in the extent of inflammation
      between the biopsies from the painful knee and the biopsies from the non-painful
      area (p = 0.5), nor between the biopsies from the abdomen, and the biopsies from
      the non-painful area (p = 0.4), in patients with DD. A statistically significant
      difference in extent of inflammation was observed between DD and obese control
      patients regarding the abdomen (p = 0.022), but not the knee (p = 0.33). There
      were no differences in extent of inflammation between DD patients and normal
      weight controls (p = 0.81). CONCLUSION: The findings suggest that there is an
      inflammatory response in the adipose tissue in DD. However, this response is not
      more pronounced than that in healthy obese controls. This contradicts
      inflammation as the aetiology of DD.

PMID- 21955698
TI  - Systematic review of the magnitude and case fatality ratio for severe maternal
      morbidity in sub-Saharan Africa between 1995 and 2010.
AB  - BACKGROUND: Analysis of severe maternal morbidity (maternal near misses) provides
      information on the quality of care. We assessed the prevalence/incidence of
      maternal near miss, maternal mortality and case fatality ratio through systematic
      review of studies on severe maternal morbidity in sub-Saharan Africa. METHODS: We
      examined studies that reported prevalence/incidence of severe maternal morbidity
      (maternal near misses) during pregnancy, childbirth and postpartum period between
      1996 and 2010. We evaluated the quality of studies (objectives, study design,
      population studied, setting and context, definition of severe acute obstetric
      morbidity and data collection instruments). We extracted data, using a pre
      defined protocol and criteria, and estimated the prevalence or incidence of
      maternal near miss. The case-fatality ratios for reported maternal complications
      were estimated. RESULTS: We identified 12 studies: six were cross-sectional, five
      were prospective and one was a retrospective review of medical records. There was
      variation in the setting: while some studies were health facility-based (at the
      national referral hospital, regional hospital or various district hospitals),
      others were community-based studies. The sample size varied from 557 women to
      23,026. Different definitions and terminologies for maternal near miss included
      acute obstetric complications, severe life threatening obstetric complications
      and severe obstetric complications. The incidence/prevalence ratio and case
      fatality ratio for maternal near misses ranged from 1.1%-10.1% and 3.1%-37.4%
      respectively. Ruptured uterus, sepsis, obstructed labor and hemorrhage were the
      commonest morbidities that were analyzed. The incidence/prevalence ratio of
      hemorrhage ranged from 0.06% to 3.05%, while the case fatality ratio for
      hemorrhage ranged from 2.8% to 27.3%. The prevalence/incidence ratio for sepsis
      ranged from 0.03% to 0.7%, while the case fatality ratio ranged from 0.0% to
      72.7%. CONCLUSION: The incidence/prevalence ratio and case fatality ratio of
      maternal near misses are very high in studies from sub-Saharan Africa. Large
      differences exist between countries on the prevalence/incidence of maternal near
      misses. This could be due to different contexts/settings, variation in the
      criteria used to define the maternal near misses morbidity, or rigor used
      carrying out the study. Future research on maternal near misses should adopt the
      WHO recommendation on classification of maternal morbidity and mortality.

PMID- 21955699
TI  - Cytochrome c maturation system on the negative side of bioenergetic membranes:
      CCB or System IV.
AB  - Cytochromes of the c-type contain hemes covalently attached via one or, more
      generally, two thioether bonds between the vinyls of heme b and the thiols of
      cysteine residues of apocytochromes. This post-translational modification relies
      on membrane-associated specific biogenesis proteins, referred to as cytochrome c
      maturation systems. At least three different versions (i.e. Systems I-III) are
      found on the positive side of bioenergetic membranes in different organisms and
      compartments. The present minireview is concerned with systems on the negative
      side of the membranes. It describes System IV, also referred to as cofactor
      assembly on complex C subunit B, for heme binding on cytochrome b(6)  through one
      thioether bond; this covalent heme is usually called c(i) . This system is found
      in all organisms with oxygenic photosynthesis but not in Firmicutes, although
      they also have a cytochrome b protein with an additional heme c(i)  covalently
      attached via a single thioether bond.

PMID- 21955700
TI  - Adaptive servo-ventilation improves renal function in patients with heart
      failure.
AB  - BACKGROUND: Impaired cardiac function and sleep-disordered breathing (SDB) are
      associated with progression of chronic kidney disease (CKD) in heart failure (HF)
      patients. Adaptive servo-ventilation (ASV) therapy improves cardiac function in
      HF patients regardless of the SDB severity through hemodynamic support and
      prevention of repetitive hypoxic stress. This study was designed to test the
      hypothesis that ASV therapy improves renal function in HF patients with SDB.
      METHODS AND RESULTS: Of 59 consecutively enrolled HF patients, 43 with moderate
      to-severe SDB underwent ASV therapy. HF patients were divided into the ASV
      treated group (n = 27) and the non-ASV-treated group (n = 16). Estimated
      glomerular filtration rate (eGFR), echocardiographic parameters, and inflammatory
      biomarkers were measured before and 12 months after ASV initiation. Improvement
      in the eGFR was found in the ASV-treated group, but not in the non-ASV-treated
      group. There was a positive correlation between the increases in eGFR and left
      ventricular ejection fraction (r = 0.488, p = 0.001). The changes in high
      sensitivity C-reactive protein were negatively correlated with change in the eGFR
      (r = -0.416, p = 0.006). CONCLUSIONS: ASV therapy could improve renal dysfunction
      in HF patients through hemodynamic support. Additionally, prevention of SDB with
      the use of ASV therapy could exert anti-inflammatory effects, which could
      contribute to the improvement of renal function in HF patients.

PMID- 21955701
TI  - More on faculty issues in academic medicine.

PMID- 21955702
TI  - How can we ease the social isolation of underrepresented minority students?

PMID- 21955706
TI  - More thoughts about residents' professionalism education in malpractice.

PMID- 21955708
TI  - Simulation is the way to bring risk management and patient safety together.

PMID- 21955710
TI  - Assessing physicians' competence.

PMID- 21955712
TI  - What is the value of an honor society?

PMID- 21955714
TI  - Commentary: The battle of Louisville: money, power, politics, and publicity at an
      academic medical center.
AB  - In 2009, the entire clinical faculty of the Department of Neurosurgery of the
      University of Louisville School of Medicine elected to become employees of a
      nearby community hospital. This took place in the context of the financial burden
      of caring for the indigent, declining reimbursement, clinical demands for
      neurosurgical coverage of a level 1 trauma center, rising salaries for
      neurosurgeons, and competitive pressure on hospitals. The author, who was dean of
      the school of medicine at the time, would not accept the abrupt withdrawal of
      these clinicians from the faculty practice plan, single-point contracting, and
      academic governance of clinical work assignments. Politicians, the press, and
      accreditation bodies quickly weighed in as the university, the school, and the
      public good were placed in jeopardy. The motivations for this event-the community
      hospital defending its market share and physician recruitment and retention
      pipeline, the dean defending principles of academic governance and the faculty
      practice plan-and the responses of the participants offer an instructive case
      study for academic medical management. The author concludes that one might view
      the protagonists of this episode not as defenders of principles but, rather, as
      pawns in a larger drama playing out related to a perfect storm of economic and
      social pressures in American medicine.

PMID- 21955715
TI  - Commentary: Teaching creativity and innovative thinking in medicine and the
      health sciences.
AB  - The National Academies of Science recently criticized the state of scientific
      innovation and competitiveness in the United States. Evaluations of already
      established creativity training programs--examining a broad array of students,
      from school age to adult and with a wide range of abilities--have shown that such
      courses improve thinking skills, attitudes, and performance. Although academic
      medicine provides informal training in creativity and innovation, it has yet to
      incorporate formal instruction on these topics into medical education. A number
      of existing, thoughtfully constructed and evaluated creativity programs in other
      fields provide a pedagogical basis for developing creativity training programs
      for the health sciences. The content of creativity training programs typically
      includes instruction and application in (1) divergent thinking, (2) problem
      solving, and (3) creative production. Instructional formats that have been shown
      to elicit the best outcomes are an admixture of lectures, discussion, and guided
      practice. A pilot program to teach innovative thinking to health science students
      at the University of Texas includes instruction in recognizing and finding
      alternatives to frames or habitual cognitive patterns, in addition to the
      constructs already mentioned. As innovation is the engine of scientific progress,
      the author, founder of Innovative Thinking, the creativity training pilot program
      at the University of Texas, argues in this commentary that academic health
      centers should implement and evaluate new methods for enhancing science students'
      innovative thinking to keep the United States as a worldwide leader in scientific
      discovery.

PMID- 21955716
TI  - Artist's statement: The last supper.

PMID- 21955718
TI  - Medicine and the arts. The prayer by Carole Bayer Sager and David Foster.
      Commentary.

PMID- 21955719
TI  - 2011 Humanism in Medicine Essay Contest: third place: The heart in my white coat.

PMID- 21955720
TI  - July first.

PMID- 21955721
TI  - AM last page: Avoiding five common pitfalls of survey design.

PMID- 21955722
TI  - [IgG4-related systemic disease: emergence of a new systemic disease? Literature
      review].
AB  - Hyper-IgG4 syndrome, or IgG4-related systemic disease (IgG4-RSD), has been
      recently characterized by the association of a focal or diffuse enlargement in
      one or more organs, elevated levels of serum IgG4 and histopathological findings
      including "storiform" fibrosis and prominent infiltration of lymphocytes and IgG4
      positive plasma cells. Pancreas was the first organ involved with sclerosing
      pancreatitis (or autoimmune pancreatitis). Since this first description, many
      extrapancreatic lesions have been described, even in the absence of pancreatitis
      and include sialadenitis, lacrimal gland inflammation, lymphadenopathy, aortitis,
      sclerosing cholangitis, tubulointerstitial nephritis, retroperitoneal fibrosis or
      inflammatory pseudotumors. Multiorgan lesions can occur synchronously or
      metachronously in a same patient, usually after 50 years of age. They all share
      common histopathological findings. The disease often responds well to
      corticosteroid therapy. In this literature review on IgG4-RSD, we present
      historical, epidemiological and clinical characteristics, and we review the
      biological and histological diagnostic criteria. To date there is no
      international validated diagnostic criteria. Pathophysiological hypothesis and
      therapeutic approaches are also discussed.

PMID- 21955723
TI  - A role of three-dimensional (3D)-reconstruction in the classification of lung
      adenocarcinoma.
AB  - BACKGROUND: Three-dimensional (3D)-reconstruction from paraffin embedded sections
      has been considered laborious and time-consuming. However, the high-resolution
      images of large object areas and different fields of view obtained by 3D
      reconstruction make one wonder whether it can add a new insight into lung
      adenocarcinoma, the most frequent histology type of lung cancer characterized by
      its morphological heterogeneity. OBJECTIVE: In this work, we tested whether an
      automated tissue sectioning machine and slide scanning system could generate
      precise 3D-reconstruction of microanatomy of the lung and help us better
      understand and define histologic subtypes of lung adenocarcinoma. METHODS: Four
      formalin-fixed human lung adenocarcinoma resections were studied. Paraffin
      embedded tissues were sectioned with Kurabo-Automated tissue sectioning machine
      and serial sections were automatically stained and scanned with a Whole Slide
      Imaging system. The resulting stacks of images were 3D reconstructed by
      Pannoramic Viewer software. RESULTS: Two of the four specimens contained islands
      of tumor cells detached in alveolar spaces that had not been described in any of
      the existing adenocarcinoma classifications. 3D-reconstruction revealed the
      details of spatial distribution and structural interaction of the tumor that
      could hardly be observed by 2D light microscopy studies. The islands of tumor
      cells extended into a deeper aspect of the tissue, and were interconnected with
      each other and with the main tumor with a solid pattern that was surrounded by
      the islands. The finding raises the question whether the islands of tumor cells
      should be classified into a solid pattern in the current classification.
      CONCLUSION: The combination of new technologies enabled us to build an effective
      3D-reconstruction of resected lung adenocarcinomas. 3D-reconstruction may help us
      refine the classification of lung adenocarcinoma by adding detailed
      spatial/structural information to 2D light microscopy evaluation.

PMID- 21955724
TI  - Seasonal change in the abundance of Synechococcus and multiple distinct
      phylotypes in Monterey Bay determined by rbcL and narB quantitative PCR.
AB  - Synechococcus is a cosmopolitan marine cyanobacterial genus, and is often the
      most abundant picocyanobacterial genus in coastal waters. Little is known about
      Synechococcus seasonal dynamics in coastal zones highly impacted by upwelling.
      This was investigated by collecting seasonal samples from an upwelling-impacted
      Monterey Bay (MB) monitoring station M0, in parallel with measurements of
      oceanographic conditions during 2006-2008. Synechococcus abundances were
      determined using quantitative PCR (qPCR) assays and flow cytometry (FCM). A new
      qPCR assay was designed to target dominant Synechococcus in MB using the rbcL
      gene, while previously designed assays targeted distinct phylotypes (called narB
      subgroups) with the narB gene. The rbcL qPCR assay successfully tracked abundant
      Synechococcus in MB, accounting for on average 89% (+/- 57%) of FCM-based counts.
      Annual spring upwelling caused decreases in Synechococcus and narB subgroup
      abundances. Differences in narB subgroup abundance maxima and abundance patterns
      support the view that subgroups differ in their ecologies, including subgroup
      D_C1, which seems to specifically thrive in coastal waters. Correlations between
      narB subgroup abundances and measured environmental variables were similar among
      the subgroups. Therefore, non-measured environmental factors (e.g. metals,
      mortality) likely had different influences on subgroups, which led to their
      distinct abundance patterns at M0.

PMID- 21955725
TI  - C-reactive protein in community-acquired sepsis: you can teach new tricks to an
      old dog.
AB  - Severe sepsis is a major challenge for clinicians caring for acutely ill
      patients. For many years, several biomarkers have been tested and proposed to
      improve the ability not only to diagnose but also to anticipate clinical response
      to antibiotics. Despite the availability of many sophisticated and novel
      biomarkers, current evidence demonstrates that C-reactive protein (CRP), a well
      known and relatively inexpensive biomarker, is useful in the clinical setting.
      The sequential evaluation of plasma CRP concentrations in patients with severe
      sepsis and the interpretation of its patterns may allow assessments of individual
      prognosis and response to treatment.

PMID- 21955726
TI  - Menstrual cycle variations in the BOLD-response to a number bisection task:
      implications for research on sex differences.
AB  - Numerical processing involves either number magnitude processing, which has been
      related to spatial abilities and relies on superior parietal regions, or
      arithmetic fact retrieval, which has been related to verbal abilities and
      involves the inferior parietal lobule. Since men score better in spatial and
      women in verbal tasks, we assume that women have advantages in fact retrieval,
      while men have benefits in number magnitude processing. According to findings on
      menstrual cycle variations in spatial and verbal abilities, fact retrieval should
      improve during the luteal phase and magnitude processing during the follicular
      phase. To dissociate sex- and menstrual cycle-dependent effects on fact retrieval
      and number magnitude processing, we applied a number bisection task in 15 men and
      15 naturally cycling women. Multiplicative items (e.g. 12_15_18) are part of a
      multiplication series and can be solved by fact retrieval, while non
      multiplicative items (e.g. 11_14_17) are not part of a multiplication series and
      require number magnitude processing. In men and women in their luteal phase,
      error rates were higher and deactivation of the medial prefrontal cortex and the
      bilateral inferior parietal lobules was stronger for non-multiplicative compared
      to multiplicative items (positive multiplicativity effect), while in the
      follicular phase women showed higher error rates and stronger deactivation in
      multiplicative compared to non-multiplicative items (negative multiplicativity
      effect). Thus, number magnitude processing improves, while arithmetic fact
      retrieval impairs during the follicular phase. While a female superiority in
      arithmetic fact retrieval could not be confirmed, we observed that sex
      differences are significantly modulated by menstrual cycle phase.

PMID- 21955727
TI  - An association study between dopamine D1 receptor gene polymorphisms and the risk
      of schizophrenia.
AB  - Deficits in dopamine transmission at D1 receptors in the PFC are implicated in
      schizophrenia. Genetic polymorphisms in functional regions of DRD1 have a
      plausible role in modulating the risk of schizophrenia. In order to evaluate the
      role of DRD1 polymorphisms as a risk factor for schizophrenia, we performed a
      detailed analysis of possible functional single nucleotide polymorphisms (SNPs)
      in regulatory and coding regions of DRD1. Nine SNPs were identified by DNA
      sequencing in 20 patients with schizophrenia. Then 385 cases and 350 healthy
      control subjects were genotyped using the nine SNPs (rs4867798, rs686, rs1799914,
      rs4532 rs5326, rs265981, rs10078714, rs10063995, rs10078866). Statistically
      significant differences were observed in the allelic or genotypic frequencies of
      the rs686 and rs10063995 polymorphism in the DRD1 gene. A significantly lower
      risk of schizophrenia was associated with the G allele and AG+GG genotype of
      rs686 (OR (G allele)=0.632, 95%CI (G allele): 0.470-0.849; OR (AG+GG
      genotype)=0.578, 95%CI (AG+GG genotype): 0.416-0.803) compared with the A allele
      and AA genotype, respectively. And a significantly increased risk of
      schizophrenia was associated with the T allele of rs10063995 (OR=1.446, 95%CI:
      1.125-1.859) compared with the G allele. The haplotype analysis indicated the G-T
      variant containing the T allele of rs10063995 is a risk for schizophrenia
      (P=0.005, OR=1.467, 95%CI: 1.123-1.917). These data suggest that DRD1 gene
      polymorphisms confer susceptibility to schizophrenia, and also support the notion
      that dysfunction of DRD1 is involved in the pathophysiological process of
      schizophrenia.

PMID- 21955728
TI  - Characterising stimulus-specific adaptation using a multi-layer field model.
AB  - The response of an auditory neuron to a tone is often affected by the context in
      which the tone appears. For example, when measuring the response to a random
      sequence of tones, frequencies that appear rarely elicit a greater number of
      spikes than those that appear often. This phenomenon is called stimulus-specific
      adaptation (SSA). This article presents a neural field model in which SSA arises
      through selective adaptation to the frequently-occurring inputs. Formulating the
      network as a field model allows one to obtain an analytical expression for the
      expected response of a simple two-layer model to tones in a random sequence. The
      sequences of stimuli used in SSA experiments contain hundreds-and sometimes
      thousands-of tones, and these experiments routinely measure the response to many
      such sequences. A conventional neural network model (e.g., integrate-and-fire)
      would require numerical integration over long time periods to obtain results.
      Consequently, a field model that offers an immediate, analytical solution for a
      given input sequence is helpful. Two routes to obtaining this solution are
      discussed. The first involves the convolution of two closed-form expressions; the
      second relies on a series of approximations involving Gaussian curves. The
      purpose of the paper is to describe the model, to develop the approximations that
      allow an analytical solution, and finally, to comment on the output of the model
      in light of the SSA results published in the physiology literature. This article
      is part of a Special Issue entitled "Neural Coding".

PMID- 21955729
TI  - Reduced expression of choline acetyltransferase in vagal motoneurons and gastric
      motor dysfunction in a 6-OHDA rat model of Parkinson's disease.
AB  - Parkinson's disease (PD) has been characterized by dopaminergic neuron
      degeneration in the substantia nigra (SN) accompanied by pathology of the dorsal
      motor nucleus of the vagus (DMV). PD patients have often experienced
      gastrointestinal dysfunctions, such as gastroparesis. However, the mechanism
      underlying these symptoms in PD patients is not clear. In the present study, we
      investigated alterations of cholinergic and catecholaminergic neurons in the DMV
      and gastric motor function in rats microinjected with 6-hydroxydopamine (6-OHDA)
      bilaterally into the SN (referred to as 6-OHDA rats) and explored possible
      mechanisms. A strain gauge force transducer was used to record gastric motility
      in vivo. Expression of choline acetyltransferase (ChAT) and tyrosine hydroxylase
      (TH) was evaluated by immunofluorescence and western blot analysis. Acetylcholine
      (Ach) content was measured using ultra-performance liquid chromatography tandem
      mass spectrometry (UPLC/MS/MS) analysis. After treatment with 6-OHDA for 6weeks,
      6-OHDA rats exhibited decreased ChAT and enhanced TH expression in the DMV and
      decreased Ach content in the gastric muscular layer. Delayed gastric emptying and
      impaired gastric motility in vivo were observed in 6-OHDA rats. The results of
      the present study indicated that decreased ChAT and enhanced TH expression in the
      DMV may be correlated with the development of delayed gastric emptying and
      impaired gastric motility, which may be partly due to the decreased Ach release
      from the vagus.

PMID- 21955730
TI  - Modeling the impact of concomitant aortic stenosis and coarctation of the aorta
      on left ventricular workload.
AB  - Coarctation of the aorta (COA) is an obstruction of the aorta and is usually
      associated with bicuspid and tricuspid aortic valve stenosis (AS). When COA
      coexists with AS, the left ventricle (LV) is facing a double hemodynamic load: a
      valvular load plus a vascular load. The objective of this study was to develop a
      lumped parameter model, solely based on non-invasive data, allowing the
      description of the interaction between LV, COA, AS and the arterial system.
      First, a formulation describing the instantaneous net pressure gradient through
      the COA was introduced and the predictions were compared to in vitro results. The
      model was then used to determine LV work induced by coexisting AS and COA with
      different severities. The results show that LV stroke work varies from 0.98J (no
      AS; no-COA) up to 2.15J (AS: 0.61cm(2)+COA: 90%). Our results also show that the
      proportion of the total flow rate that will cross the COA is significantly
      reduced with the increasing COA severity (from 85% to 40%, for a variation of COA
      severity from 0% to 90%, respectively). Finally, we introduced simple
      formulations capable of, non-invasively, estimating both LV peak systolic
      pressure and workload. As a conclusion, this study allowed the development of a
      lumped parameter model, based on non-invasive measurements, capable of accurately
      investigating the impact of coexisting AS and COA on LV workload. This model can
      be used to optimize the management of patients with COA and AS in terms of the
      sequence of lesion repair.

PMID- 21955731
TI  - Major bleeding during negative pressure wound/V.A.C.(r)--therapy for postsurgical
      deep sternal wound infection--a critical appraisal.
AB  - Negative-pressure wound therapy, commercially known as vacuum-assisted closure
      (V.A.C.(r)) therapy, has become one of the most popular (and efficacious) interim
      (prior to flap reconstruction) or definite methods of managing deep sternal wound
      infection. Complications such as profuse bleeding, which may occur during
      negative-pressure therapy but not necessarily due to it, are often attributed to
      a single factor and reported as such. However, despite the wealth of clinical
      experience internationally available, information regarding certain simple
      considerations is still lacking. Garnering information on all the factors that
      could possibly influence the outcome has become more difficult due to a
      (fortunate) decrease in the incidence of deep sternal wound infection. If more
      insight is to be gained from fewer clinical cases, then various potentially
      confounding factors should be fully disclosed before complications can be
      attributed to the technique itself or improvements to negative-pressure wound
      therapy for deep sternal wound infection can be accepted as evidence-based and
      the guidelines for its use adapted. The authors propose the adoption of a simple
      checklist in such cases.

PMID- 21955732
TI  - Epidemiology and risk management of listeriosis in India.
AB  - Listeria monocytogenes is a foodborne pathogen that can cause serious invasive
      illness, mainly in certain well-defined high-risk groups, including elderly and
      immunocompromised patients, pregnant women, newborns and infants. In India, this
      pathogen has been isolated from humans, animals and foods. The incidence of
      Listeria is generally comparable to those reported elsewhere in the world. In
      humans, maternal/neonatal listeriosis is the most common clinical form reported.
      Among animal populations, spontaneous abortions, subclinical mastitis,
      meningoencephalitis and endometritis were the commonest forms reported. The
      disease largely remains undiagnosed and under reported. From reported analyses of
      a variety of foods for Listeria, milk and milk products, meat and meat products,
      seafood and vegetables have been reported to be contaminated in India. The legal
      framework for microbiological safety of foods against microbes including L.
      monocytogenes is summarised. The epidemiological studies would help in
      understanding of the sources of infection and persistence and their risk
      assessment, routes of transmission, clinical forms and allow for better
      management of the infection.

PMID- 21955733
TI  - Adverse health consequences in COPD patients with rapid decline in FEV1--evidence
      from the UPLIFT trial.
AB  - BACKGROUND: The rate of decline in forced expiratory volume in 1 second (FEV1) is
      representative of the natural history of COPD. Sparse information exists
      regarding the associations between the magnitude of annualised loss of FEV1 with
      other endpoints. METHODS: Retrospective analysis of UPLIFT(r) trial (four-year,
      randomized, double-blind, placebo-controlled trial of tiotropium 18 MUg daily in
      chronic obstructive pulmonary disease [COPD], n = 5993). Decline of FEV1 was
      analysed with random co-efficient regression. Patients were categorised according
      to quartiles based on the rate of decline (RoD) in post-bronchodilator FEV1. The
      St George's Respiratory Questionnaire (SGRQ) total score, exacerbations and
      mortality were assessed within each quartile. RESULTS: Mean (standard error [SE])
      post-bronchodilator FEV1 increased in the first quartile (Q1) by 37 (1) mL/year.
      The other quartiles showed annualised declines in FEV1 (mL/year) as follows: Q2 =
      24 (1), Q3 = 59 (1) and Q4 = 125 (2). Age, gender, respiratory medication use at
      baseline and SGRQ did not distinguish groups. The patient subgroup with the
      largest RoD had less severe lung disease at baseline and contained a higher
      proportion of current smokers. The percentage of patients with >= 1 exacerbation
      showed a minimal difference from the lowest to the largest RoD, but exacerbation
      rates increased with increasing RoD. The highest proportion of patients with >= 1
      hospitalised exacerbation was in Q4 (Q1 = 19.5% [tiotropium], 26% [control]; Q4 =
      33.8% [tiotropium] and 33.1% [control]). Time to first exacerbation and
      hospitalised exacerbation was shorter with increasing RoD. Rate of decline in
      SGRQ increased in direct proportion to each quartile. The group with the largest
      RoD had the highest mortality. CONCLUSION: Patients can be grouped into different
      RoD quartiles with the observation of different clinical outcomes indicating that
      specific (or more aggressive) approaches to management may be needed. TRIAL
      REGISTRATION: ClinicalTrials.gov number, NCT00144339.

PMID- 21955734
TI  - Selected eating behaviours and excess body weight: a systematic review.
AB  - The relationship between obesity and the intake of macronutrients and specific
      foods is uncertain. Thus, there is growing interest in some eating behaviours
      because they may reflect the joint effect of several foods and nutrients and,
      thus, increase the likelihood of finding a link to obesity. This study examined
      the association between selected eating behaviours and excess weight in the
      general population throughout a systematic review of publications written in
      English, Spanish or Portuguese identified in a PubMed search up to 31 December
      2010. We included 153 articles, 73 of which have been published since 2008. Only
      30 studies had a prospective design; of these, 15 adjusted for sociodemographic
      variables, physical activity and energy or food intake. Moreover, definitions of
      eating behaviours varied substantially across studies. We found only small or
      inconsistent evidence of a relationship between excess weight and skipping
      breakfast, daily eating frequency, snacking, irregular meals, eating away from
      home, consumption of fast food, takeaway food intake, consumption of large food
      portions, eating until full and eating quickly. In conclusion, this review
      highlights the difficulty in measuring human behaviour, and suggests that a more
      systematic approach is needed for capturing the effects of eating behaviours on
      body weight.

PMID- 21955735
TI  - The impact of gastrointestinal parasites infection on slaughter efficiency in
      pigs.
AB  - The aim of the present study was to determine an influence of parasites invasion
      on fodder consumption and slaughter yield of fatteners in three different
      maintenance systems. The experimental part of the study was conducted on pigs
      farm producing in a close cycle. The study on internal parasites of fatteners
      were conducted based on coproscopic methods. In order to describe the
      relationship between following variables: meatiness, slaughter yield, fodder
      consumption and mean EPG value, the principal component analysis (PCA) was used.
      The analysis between fodder consumption and maintenance system and fodder
      consumption and helminths infection did not demonstrate any significant
      relationship. The analysis between slaughter yield and meatiness and an infection
      demonstrated in turn a decrease in both parameters values in the two maintenance
      systems, i.e. in fatteners kept on litter meatiness decrease in infected
      fatteners of 4.2% and yield of 1.7%. On slatted floor meatiness decrease in
      infected fatteners of 6.1% and yield of 2.7%. The decreasing tendency in meat
      content (3.7%) and in slaughter yield (1.1%) was also observed in fatteners
      maintained on deep litter, however the values were not significant statistically.

PMID- 21955736
TI  - Antigen-specific antibody isotypes, lymphocyte subsets and cytokine profiles in
      cattle naturally infested by Hypoderma sp. (Diptera: Oestridae).
AB  - Antigen-specific antibody responses, T cell subsets and cytokine profiles were
      studied in 7 heifers naturally infested by Hypoderma sp. in Northwestern Spain.
      Immunoglobulin G (IgG) levels increased significantly at the end of the
      endogenous life cycle of the parasite (Mr). Similarly, IgG1 subclass increased
      considerably when first instars (L1) started their migration towards the back (Nv
      Ja), whereas IgG2 increased earlier, coinciding with the arrival of L1 to the
      resting sites (Jn-Jl). Both subclasses decreased significantly when L3 began to
      leave the host. IgM levels and CD4 and CD8 profiles hardly oscillated throughout
      the life cycle of the parasite into the host. The CD4/CD8 ratio showed helper T
      cell predominance. Serum interferon-gamma (IFN-gamma) concentrations decreased
      from October to the end of the study. Interleukin 4 (IL-4) concentrations
      decreased in January and increased in February and May. There were a significant
      positive relationship between IL-4 and IgG2 subclass and a negative correlation
      between IFN-gamma, IgG and IgG1 and also between IgM and CD2 and CD8 counts.
      These results suggest that in the early phases of natural primoinfestations by
      Hypoderma there is a slight predominance of a Th1 response, characterized by high
      IgG2 and IFN-gamma levels, which is followed by a Th2 response with a clear
      predominance of IgG1 and IL-4.

PMID- 21955737
TI  - First record of Taenia ovis krabbei muscle cysts in muskoxen from Greenland.
AB  - A first record of Taenia ovis krabbei muscle cysts in a muskoxen (Ovibos
      moschatus) from the Kangerlussuaq population in West Greenland suggests that
      introduced muskoxen now contributes to the transmission of this parasite in
      addition to previous observations from caribou (Rangifer tarandus). Muskoxen and
      caribou are the only wild ungulates in Greenland.

PMID- 21955738
TI  - Scientists and public involvement: a consultation on the relation between
      malaria, vector control and transgenic mosquitoes.
AB  - Among the hopes for vector-based malaria control, the use of transgenic
      mosquitoes able to kill malaria parasites is seen as a potential way to interrupt
      malaria transmission. While this potential solution is gaining some support, the
      ethical and social aspects related to this high-tech method remain largely
      unexplored and underestimated. Related to those latter points, the aim of the
      present survey is to determine how scientists working on malaria and its vector
      mosquitoes perceive public opinion and how they evaluate public consultations on
      their research. This study has been performed through a questionnaire addressing
      questions related to the type of research, the location, the nationality and the
      perception of the public involvement by scientists. The results suggest that even
      if malaria researchers agree to interact with a non-scientific audience, they
      (especially the ones from the global North) remain quite reluctant to have their
      research project submitted in a jargon-free version to the evaluation and the
      prior-agreement by a group of non-specialists. The study, by interrogating the
      links between the scientific community and the public from the perspective of the
      scientists, reveals the importance of fostering structures and processes that
      could lead to a better involvement of a non specialist public in the actual
      debates linking scientific, technological and public health issues in Africa.

PMID- 21955739
TI  - Serological response to Bartonella species in febrile patients from Nepal.
AB  - The Bartonella-associated illnesses are spread world-wide and involve a broad
      spectrum of signs and symptoms in humans. Several Bartonella species have been
      shown to be responsible for cases of febrile illnesses. Little information exists
      on distribution of Bartonella species and their role in human diseases in Nepal.
      Our preliminary study, a retrospective serological survey of archived specimens,
      suggests that Bartonella antibodies are prevalent among febrile patients in the
      Kathmandu Valley of Nepal.

PMID- 21955740
TI  - Medium-term outcomes of patients with insulin-dependent diabetes after
      laparoscopic adjustable gastric banding.
AB  - BACKGROUND: Bariatric surgery is effective in the control of type 2 diabetes
      mellitus. Laparoscopic adjustable gastric banding is a popular form of bariatric
      surgery, but very limited data are available on its long-term effect on type 2
      diabetes mellitus. The present study examined the effect of gastric banding on a
      consecutive cohort of unselected patients with insulin-dependent diabetes
      mellitus at a teaching hospital in Birmingham, United Kingdom. METHODS: From
      April 2003 to December 2008, 200 patients with diabetes underwent laparoscopic
      adjustable gastric banding at our unit. All those with insulin-dependent diabetes
      and >=1 year of follow-up were included in the present analysis. Data collection
      included the body mass index, weight, blood pressure, glycosylated hemoglobin,
      fasting glucose, total cholesterol, triglycerides, and medication dose
      preoperatively and 1, 2, and 3 years postoperatively. RESULTS: Preoperatively, 69
      patients were taking insulin, with a mean daily preoperative dose of 132.3 U
      (range 15-500). At 1 year, 27 of these patients had discontinued using insulin
      (34.8%). At 2 years, 34 patients had discontinued using insulin (54.8% of the
      patients taking insulin preoperatively and who had also completed 2 yr of follow
      up). At 3 years, 40 patients had discontinued using insulin (80% of patients who
      were taking insulin preoperatively and who had also completed 3 yr of follow-up).
      These changes were accompanied by an improvement in glycosylated hemoglobin,
      fasting glucose, total serum cholesterol, triglycerides, and mean arterial
      pressures. CONCLUSION: Laparoscopic gastric banding can be considered a powerful
      treatment option in the management of obese patients with insulin-dependent
      diabetes and becomes increasingly effective with time <=3 years after surgery.

PMID- 21955741
TI  - American Society for Metabolic and Bariatric Surgery position statement on global
      bariatric healthcare.

PMID- 21955742
TI  - Laparoscopic adjustable gastric banding over previous duodenal switch: weight
      results from short-term follow-up.

PMID- 21955743
TI  - Gastroesophageal reflux after sleeve gastrectomy in morbidly obese patients.
AB  - BACKGROUND: Gastroesophageal reflux disease (GERD) is highly prevalent in
      morbidly obese patients and a high body mass index is a risk factor for the
      development of this co-morbidity. The effect of laparoscopic sleeve gastrectomy
      (LSG) on GERD is poorly known. METHODS: We studied the effect of LSG on GERD in
      patients with morbid obesity. A retrospective review of 28 consecutive patients
      undergoing LSG for morbid obesity from September 2008 to September 2010 was
      performed. RESULTS: A total of 28 patients, 18 women and 10 men, were identified,
      with a mean age of 42 years (range 18-60). The mean weight and body mass index
      was 166 kg and 55.5 kg/m2, respectively. The mean percentage of excess weight
      loss was 40% (range 17-83), with a mean follow-up time of 32 weeks (range 8-92).
      All patients had a pre- and postoperative upper gastrointestinal radiographic
      swallow study as a part of their routine care. Of these patients, 18% were noted
      to have new-onset GERD on their postoperative upper gastrointestinal swallow test
      after their LSG procedure. Using the GERD score questionnaire, all patients were
      interviewed to evaluate their reflux symptoms. We had a 64% response rate, with
      22% of patients indicating new-onset GERD symptoms despite receiving daily
      antireflux therapy. All respondents were extremely happy with their surgery and
      weight loss to date. CONCLUSION: LSG might increase the prevalence of GERD
      despite satisfactory weight loss. Additional studies evaluating esophageal
      manometry and ambulatory 24-hours pH-metry are needed to better evaluate the
      effect of LSG on gastroesophageal reflux symptoms.

PMID- 21955744
TI  - Implantation of the duodenal-jejunal bypass sleeve under conscious sedation: a
      case series.

PMID- 21955745
TI  - Laparoscopic removal of eroded laparoscopic adjustable gastric band.

PMID- 21955746
TI  - Distal airway dysfunction in obese subjects corrects after bariatric surgery.
AB  - BACKGROUND: Obesity is frequently associated with respiratory symptoms despite
      normal large airway function as assessed by spirometry. However, reduced
      functional residual capacity and expiratory reserve volume are common and might
      reflect distal airway dysfunction. Impulse oscillometry (IOS) might identify
      distal airway abnormalities not detected using routine spirometry screening. Our
      objective was to test the hypothesis that excess body weight will result in
      distal airway dysfunction detected by IOS that reverses after bariatric surgery.
      The setting was a university hospital. METHODS: A total of 342 subjects underwent
      spirometry, plethysmography, and IOS before bariatric surgery. Of these patients,
      75 repeated the testing after the loss of 20% of the total body weight. The data
      from 47 subjects with normal baseline spirometry and complete pre- and
      postoperative data were analyzed. RESULTS: IOS detected preoperative distal
      airway dysfunction despite normal spirometry findings by an abnormal airway
      resistance at an oscillation frequency of 20 Hz (4.75 +/- 1.2 cm H2O/L/s),
      frequency dependence of resistance from 5 to 20 Hz (2.20 +/- 1.6 cm H2O/L/s), and
      reactance at 5 Hz (-3.47 +/- 2.1 cm H2O/L/s). Postoperatively, the subjects
      demonstrated 57% +/- 15% excess weight loss. The body mass index decreased (from
      44 +/- 6 to 32 +/- 5 kg/m2, P < .001). Improvements in functional residual
      capacity (from 59% +/- 11% to 75% +/- 20% predicted, P < .001) and expiratory
      reserve volume (from 41% +/- 20% to 75% +/- 20% predicted, P < .001) were
      demonstrated. Distal airway function also improved: airway resistance at an
      oscillation frequency of 20 Hz (3.91 +/- .9, P < .001), frequency dependence of
      resistance from 5 to 20 Hz (1.17 +/- .9, P < .001), and reactance at 5 Hz (-1.85
      +/- .9, P < .001). CONCLUSION: The present study detected significant distal
      airway dysfunction despite normal preoperative spirometry findings. The effect of
      increased body weight was likely the main mechanism for these abnormalities.
      However, the inflammatory state of obesity or associated respiratory disease
      could also be invoked. These abnormalities improved significantly toward normal
      after weight loss. The results of the present study highlight the importance of
      bariatric surgery as an effective intervention in reversing these respiratory
      abnormalities.

PMID- 21955747
TI  - Pregnancy after laparoscopic bariatric surgery: comparative study of adjustable
      gastric banding and Roux-en-Y gastric bypass.
AB  - BACKGROUND: Approximately 80% of patients undergoing bariatric surgery are women,
      and about one half of these are of reproductive age. The purpose of the present
      study was to compare laparoscopic adjustable gastric banding (LAGB) and
      laparoscopic Roux-en-Y gastric bypass (LRYGB) in a series of morbidly obese women
      with respect to maternal and neonatal outcomes at a university hospital in
      France. METHODS: From January 2004 to December 2008, the data from women who had
      undergone LAGB or LRYGB at our center and were pregnant were collected, including
      age, parity, gravidity, weight, body mass index (BMI) before surgery and at
      scheduled intervals after surgery (1, 3, 6, 12, and 18 mo and yearly thereafter),
      interval from surgery to conception, weight and BMI at conception, weight and
      weight gain during pregnancy, weight and BMI at 2 weeks after pregnancy,
      complications during pregnancy, gestational age, method of delivery, fetal birth
      weight, and fetal outcome. RESULTS: There were 42 pregnancies in 36 women, 22 in
      women who had undergone LAGB and 20 who had undergone LRYGB. The LAGB and LRYGB
      groups were comparable for all analyzed variables, except that the preoperative
      weight and BMI were greater in the LRYGB group. No differences in weight or BMI
      were found at conception or after pregnancy. No difference was found between the
      2 groups in terms of obstetric complications or neonatal outcomes. A high
      frequency of cesarean deliveries was necessary in both groups. CONCLUSIONS: The
      results of the present study have shown that no significant difference exists in
      the obstetric and birth outcomes between women who have undergone LRYGB and those
      who have undergone LAGB.

PMID- 21955748
TI  - Single port sleeve gastrectomy: strategic use of technology to re-establish
      fundamental tenets of multiport laparoscopy.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy is commonly performed using multiple
      ports. The quest to minimize surgical trauma has led to the development of single
      port laparoscopy, which has been shown to be a safe, less-invasive method of
      performing a variety of abdominal surgeries. We describe the feasibility and
      safety of single port sleeve gastrectomy (SPSG) for morbid obesity at an academic
      affiliate of a university hospital. METHODS: A total of 25 patients undergoing
      elective SPSG were compared with a demographically similar contemporaneous cohort
      of 9 patients who underwent standard multiple port laparoscopic sleeve
      gastrectomy. The data collected included the operative time, narcotic
      consumption, duration of patient controlled analgesia use, subjective pain
      scores, and length of stay. RESULTS: The patients undergoing SPSG experienced
      significantly less pain at 1 hour postoperatively (P = .039). No statistically
      significant difference was found in pain between the 2 groups at 12 and 24 hours
      (P = .519 and P = .403, respectively). The quantity of narcotic use (P = .538),
      duration of patient controlled analgesia use (P = .820), and length of stay (P =
      .571) were not significantly different between the 2 groups. The operative time
      for SPSG was 118 minutes versus 101 minutes for multiple port surgery (P = .160).
      CONCLUSIONS: SPSG is safe and feasible for selected patients. The patients
      undergoing SPSG reported significantly less pain at the first postoperative hour.
      No significant differences between the 2 groups were seen in any of the other
      postoperative parameters.

PMID- 21955750
TI  - The utility of multidetector computed tomography for detection of parathyroid
      disease in the setting of primary hyperparathyroidism.
AB  - PURPOSE: The aim of this study was to evaluate the accuracy of multidetector
      computed tomography (MDCT) in the detection of parathyroid adenoma and
      hyperplasia in the setting of primary hyperparathyroidism. METHODS: Records of 48
      patients with biochemically confirmed primary hyperparathyroidism, who underwent
      preoperative imaging with 16- or 64-slice contrast-enhanced MDCT and subsequent
      successful parathyroidectomy over a 3-year period, were reviewed. Two
      radiologists, blinded to the operative and histologic findings, independently
      evaluated multiplanar computed tomographic images for all patients. RESULTS: On
      pathologic examination, 63 abnormal glands were confirmed in 41 female and 7 male
      patients (mean age, 63 years). Of the 63 abnormal glands, 40 were adenomatous and
      23 were hyperplastic. MDCT demonstrated an 88% (95% confidence interval [CI], 77%
      99%) positive predictive value for localizing abnormal hyperfunctioning
      parathyroid glands. The sensitivity of MDCT in detecting single-gland disease was
      80% (95% CI, 68%-92%); whereas the specificity for ruling out hyperfunctioning
      parathyroid tissue, either adenomatous or hyperplastic, was 75% (95% CI, 51%
      99%). The sensitivity for exclusively localizing parathyroid hyperplasia was 17%
      (95% CI, 2%-33%). The parathyroid adenomas were substantially larger and heavier
      than their hyperplastic counterparts, with an average weight of 1.51 g (range,
      0.08-6.00 g) and 0.42 g (range, 0.02-2.0 g) for adenoma and hyperplasia,
      respectively. CONCLUSIONS: Contrast-enhanced MDCT demonstrated an 88% positive
      predictive value for localizing adenomatous and hyperplastic parathyroid glands.
      The poor sensitivity for detection of multigland disease was likely a result of
      the smaller size and weight of the abnormal hyperplastic glands.

PMID- 21955749
TI  - Rasch analysis of the hospital anxiety and depression scale (HADS) for use in
      motor neurone disease.
AB  - BACKGROUND: The Hospital Anxiety and Depression Scale (HADS) is commonly used to
      assess symptoms of anxiety and depression in motor neurone disease (MND). The
      measure has never been specifically validated for use within this population,
      despite questions raised about the scale's validity. This study seeks to analyse
      the construct validity of the HADS in MND by fitting its data to the Rasch model.
      METHODS: The scale was administered to 298 patients with MND. Scale assessment
      included model fit, differential item functioning (DIF), unidimensionality, local
      dependency and category threshold analysis. RESULTS: Rasch analyses were carried
      out on the HADS total score as well as depression and anxiety subscales (HADS-T,
      D and A respectively). After removing one item from both of the seven item
      scales, it was possible to produce modified HADS-A and HADS-D scales which fit
      the Rasch model. An 11-item higher-order HADS-T total scale was found to fit the
      Rasch model following the removal of one further item. CONCLUSION: Our results
      suggest that a modified HADS-A and HADS-D are unidimensional, free of DIF and
      have good fit to the Rasch model in this population. As such they are suitable
      for use in MND clinics or research. The use of the modified HADS-T as a higher
      order measure of psychological distress was supported by our data. Revised cut
      off points are given for the modified HADS-A and HADS-D subscales.

PMID- 21955752
TI  - Composition and function of cytochrome c biogenesis System II.
AB  - Organisms employ one of several different enzyme systems to mature cytochromes c.
      The biosynthetic process involves the periplasmic reduction of cysteine residues
      in the heme c attachment motif of the apocytochrome, transmembrane transport of
      heme b and stereospecific covalent heme attachment via thioether bonds. The
      biogenesis System II (or Ccs system) is employed by beta-, delta- and epsilon
      proteobacteria, Gram-positive bacteria, Aquificales and cyanobacteria, as well as
      by algal and plant chloroplasts. System II comprises four (sometimes only three)
      membrane-bound proteins: CcsA (or ResC) and CcsB (ResB) are the components of the
      cytochrome c synthase, whereas CcdA and CcsX (ResA) function in the generation of
      a reduced heme c attachment motif. Some epsilon-proteobacteria contain CcsBA
      fusion proteins constituting single polypeptide cytochrome c synthases especially
      amenable for functional studies. This minireview highlights the recent findings
      on the structure, function and specificity of individual System II components and
      outlines the future challenges that remain to our understanding of the
      fascinating post-translational protein maturation process in more detail.

PMID- 21955751
TI  - Calcium ionophore A23187 reveals calcium related cellular stress as "I-Bodies":
      an old actor in a new role.
AB  - Calcimycin (A23187) is an ionophore widely used in studies related to calcium
      dynamics in cells, but its fluorometric potential to reveal intracellular
      physiology has not been explored. Exploiting the microenvironment-induced changes
      in its fluorescence, we show that a brief exposure of cells to non-toxic
      concentrations (<=3MUM) of the ionophore results in the characteristic
      organization of the ionophore forming brightly fluorescent cytoplasmic bodies
      termed "I-Bodies", which are closely related to stress linked
      disturbances/changes in calcium homeostasis. "I-Bodies" appear to be Ca(2+) rich
      intracellular sites formed during stress-induced release of intracellular Ca(2+),
      causing dysfunction and aggregation of mitochondria, providing scaffold for high
      density packing of A23187. Formation of "I-Bodies" in cells exposed to ionizing
      radiation and certain anticancer drugs suggest their potential in revealing
      alterations in calcium signaling and mitochondrial function during (related to)
      macromolecular damage-induced cell death. The absence of "I-Bodies" in non
      malignant cells and their varying numbers in malignant cells with 5 fold increase
      in fluorescence imply that they can be potential biomarkers of cancer. Thus, "I
      Bodies" are novel indicators of endogenous and induced stress linked to
      disturbances in calcium homeostasis in cells, with a potential to serve as
      biomarker of cancer.

PMID- 21955754
TI  - A polymer nanostructured Fabry-Perot interferometer based biosensor.
AB  - A polymer nanostructured Fabry-Perot interferometer (FPI) based biosensor is
      reported. Different from a conventional FPI, the nanostructured FPI has a layer
      of Au-coated nanopores inside its cavity. The Au-coated nanostructure layer
      offers significant enhancement of optical transducing signals due to the
      localized surface plasmon resonance effect and also due to the significantly
      increased sensing surface area, which is up to at least two orders of magnitude
      larger than that of a conventional FPI-based biosensor. Using this technical
      platform, the immobilization of captures proteins (protein A) on the
      nanostructure layer and their binding with immunoglobulin G (IgG) has been
      monitored in real time, resulting in the shift of the interference fringes of the
      optical transducing signals. Current results show that the limit-of-detection of
      the biosensor should be lower than 10 pg/mL for IgG-protein A binding.

PMID- 21955753
TI  - Cyclin D1, Id1 and EMT in breast cancer.
AB  - BACKGROUND: Cyclin D1 is a well-characterised cell cycle regulator with
      established oncogenic capabilities. Despite these properties, studies report
      contrasting links to tumour aggressiveness. It has previously been shown that
      silencing cyclin D1 increases the migratory capacity of MDA-MB-231 breast cancer
      cells with concomitant increase in 'inhibitor of differentiation 1' (ID1) gene
      expression. Id1 is known to be associated with more invasive features of cancer
      and with the epithelial-mesenchymal transition (EMT). Here, we sought to
      determine if the increase in cell motility following cyclin D1 silencing was
      mediated by Id1 and enhanced EMT-features. To further substantiate these findings
      we aimed to delineate the link between CCND1, ID1 and EMT, as well as clinical
      properties in primary breast cancer. METHODS: Protein and gene expression of ID1,
      CCND1 and EMT markers were determined in MDA-MB-231 and ZR75 cells by western
      blot and qPCR. Cell migration and promoter occupancy were monitored by transwell
      and ChIP assays, respectively. Gene expression was analysed from publicly
      available datasets. RESULTS: The increase in cell migration following cyclin D1
      silencing in MDA-MB-231 cells was abolished by Id1 siRNA treatment and we
      observed cyclin D1 occupancy of the Id1 promoter region. Moreover, ID1 and SNAI2
      gene expression was increased following cyclin D1 knock-down, an effect reversed
      with Id1 siRNA treatment. Similar migratory and SNAI2 increases were noted for
      the ER-positive ZR75-1 cell line, but in an Id1-independent manner. In a meta
      analysis of 1107 breast cancer samples, CCND1low/ID1high tumours displayed
      increased expression of EMT markers and were associated with reduced recurrence
      free survival. Finally, a greater percentage of CCND1low/ID1high tumours were
      found in the EMT-like 'claudin-low' subtype of breast cancer than in other
      subtypes. CONCLUSIONS: These results indicate that increased migration of MDA-MB
      231 cells following cyclin D1 silencing can be mediated by Id1 and is linked to
      an increase in EMT markers. Moreover, we have confirmed a relationship between
      cyclin D1, Id1 and EMT in primary breast cancer, supporting our in vitro findings
      that low cyclin D1 expression can be linked to aggressive features in subgroups
      of breast cancer.

PMID- 21955755
TI  - Monitoring oxygen consumption of single mouse embryos using an integrated
      electrochemical microdevice.
AB  - Oxygen consumption (respiration activity) has been found to be the most
      remarkable criterion for determining the viability of an embryo produced in
      vitro. In this study, we propose an accurate, simple, and user-friendly device
      for measurement of the oxygen consumption of single mammalian embryos. An
      integrated electrode array was fabricated to determine the oxygen consumption of
      a single embryo, including the blastocyst stage, which has an inhomogeneous
      oxygen consumption rate, using a single measurement procedure. A single mouse
      embryo was positioned in a microwell at the center of an integrated electrode
      array, using a mouthpiece pipette, and immobilized by a cylindrical micropit with
      good reproducibility. The oxygen consumption of two-cell, morula, and blastocyst
      stages was measured amperometrically using the device. The recorded current
      profile was corrected to take into consideration transient background current
      during the measurement. A calculation method for oxygen consumption based on
      spherical diffusion centered on the defined point of the device was developed.
      This procedure is quite simple because it is not necessary to estimate the radius
      of the embryo being measured. The calculated values of oxygen consumption for two
      cell, morula, and blastocyst stages were 1.36+/-0.33*10(-15) mol s(-1), 1.38+/
      0.58*10(-15) mol s(-1), and 3.44+/-2.07*10(-15) mol s(-1), respectively. The
      increasing pattern of oxygen consumption from morula to blastocyst agreed well
      with measurements obtained using conventional scanning electrochemical microscopy
      (SECM).

PMID- 21955756
TI  - Nonenzymatic electrochemical detection of glucose using well-distributed nickel
      nanoparticles on straight multi-walled carbon nanotubes.
AB  - A nonenzymatic electrochemical sensor device was fabricated for glucose detection
      based on nickel nanoparticles (NiNPs)/straight multi-walled carbon nanotubes
      (SMWNTs) nanohybrids, which were synthesized through in situ precipitation
      procedure. SMWNTs can be easily dispersed in solution after mild sonication
      pretreatment, which facilitates the precursor of NiNPs binding to their surface
      and results in the homogeneous distribution of NiNPs on the surface of SMWNTs.
      The morphology and component of the nanohybrids were characterized by scanning
      electron microscopy (SEM) and X-ray powder diffraction (XRD), respectively.
      Cyclic voltammetry (CV) and amperometry were used to evaluate the catalytic
      activity of the NiNPs/SMWNTs nanohybrids modified electrode towards glucose. It
      was found that the nanohybrids modified electrode showed remarkably enhanced
      electrocatalytic activity towards the oxidation of glucose in alkaline solution
      compared to that of the bare glass carbon electrode (GCE), the NiNPs and the
      SMWNTs modified electrode, attributing to the synergistic effect of SMWNTs and
      Ni(2+)/Ni(3+) redox couple. Under the optimal detection conditions, the as
      prepared sensors exhibited linear behavior in the concentration range from 1 MUM
      to 1 mM for the quantification of glucose with a limit of detection of 500 nM
      (3sigma). Moreover, the NiNPs/SMWNTs modified electrode was also relatively
      insensitive to commonly interfering species such as ascorbic acid (AA), uric acid
      (UA), dopamine (DA), galactose (GA), and xylose (XY). The robust selectivities,
      sensitivities, and stabilities determined experimentally indicated the great
      potential of NiNPs/SMWNTs nanohybrids for construction of a variety of
      electrochemical sensors.

PMID- 21955759
TI  - Rater-based assessments as social judgments: rethinking the etiology of rater
      errors.
AB  - BACKGROUND: Measurement errors are a limitation of using rater-based assessments
      that are commonly attributed to rater errors. Solutions targeting rater
      subjectivity have been largely unsuccessful. METHOD: This critical review
      examines investigations of rater idiosyncrasy from impression formation
      literatures to ask new questions for the parallel problem in rater-based
      assessments. RESULTS: Raters may form categorical judgments about ratees as part
      of impression formation. Although categorization can be idiosyncratic, raters
      tend to consistently construct one of a few possible interpretations of each
      ratee. If raters naturally form categorical judgments, an assessment system
      requiring ordinal or interval ratings may inadvertently introduce conversion
      errors due to translation techniques unique to each rater. CONCLUSIONS: Potential
      implications of raters forming differing categorizations of ratees combined with
      the use of rating scales to collect categorical judgments on measurement outcomes
      in rater-based assessments are explored.

PMID- 21955757
TI  - Short-term effects of combining upright and prone positions in patients with
      ARDS: a prospective randomized study.
AB  - INTRODUCTION: Prone position is known to improve oxygenation in patients with
      acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS).
      Supine upright (semirecumbent) position also exerts beneficial effects on gas
      exchange in this group of patients. We evaluated the effect of combining upright
      and prone position on oxygenation and respiratory mechanics in patients with ALI
      or ARDS in a prospective randomized cross-over study. METHODS: After turning them
      prone from a supine position, we randomized the patients to a prone position or
      combined prone and upright position. After 2 hours, the position was changed to
      the other one for another 6 hours. The gas exchange and static compliance of the
      respiratory system, lungs, and chest wall were assessed in the supine position as
      well as every hour in the prone position. RESULTS: Twenty patients were enrolled
      in the study. The PaO2/FiO2 ratio improved significantly from the supine to the
      prone position and further significantly increased with additional upright
      position. Fourteen (70%) patients were classified as responders to the prone
      position, whereas 17 (85%) patients responded to the prone plus upright position
      compared with the supine position (P = n.s.). No statistically significant
      changes were found with respect to compliance. CONCLUSIONS: Combining the prone
      position with the upright position in patients with ALI or ARDS leads to further
      improvement of oxygenation. TRIAL REGISTRATION: Clinical Trials No. NCT00753129.

PMID- 21955760
TI  - Learning in the simulated setting: a comparison of expert-, peer-, and computer
      assisted learning.
AB  - PURPOSE: To compare the effectiveness of expert-assisted learning (EAL), peer
      assisted learning (PAL), and computer-assisted learning (CAL) on participants'
      procedural skills acquisition in the simulated setting. METHOD: Sixty medical and
      nursing students practiced urinary catheterization in an expert-, peer- or
      computer-assisted, simulation-based, learning environment. Effectiveness of
      training was evaluated in the simulated setting using an immediate posttest and,
      one week later, on a retention and standardized patient-based transfer test.
      Measures included number of breaks in aseptic technique and blinded expert
      assessments. RESULTS: All groups performed similarly on the pre-, post-, and
      retention tests. At transfer, the EAL group performed significantly better than
      the PAL group as measured by global clinical performance, catheterization
      checklist scores, and number of breaks in aseptic technique (P < .05).
      Communication and catheterization global ratings were equivalent for all groups
      (P > .05). CONCLUSIONS: CAL is as effective as expert feedback for teaching
      procedural skills to novices in the simulated setting. When extrinsic feedback is
      provided, the expertise level of the teacher seems to be a critical factor
      influencing effectiveness of training, with EAL being more effective than PAL.

PMID- 21955761
TI  - A multilevel analysis of examinee gender, standardized patient gender, and United
      States medical licensing examination step 2 clinical skills communication and
      interpersonal skills scores.
AB  - BACKGROUND: Women typically demonstrate stronger communication skills on
      performance-based assessments using human raters in medical education settings.
      This study examines the effects of examinee and rater gender on communication and
      interpersonal skills (CIS) scores from the performance-based component of the
      United States Medical Licensing Examination, the Step 2 Clinical Skills (CS)
      examination. METHOD: Data included demographic and performance information for
      examinees that took Step 2 CS for the first time in 2009. The sample contained
      27,910 examinees, 625 standardized patient/case combinations, and 278,776 scored
      patient encounters. Hierarchical linear modeling techniques were employed with
      CIS scores as the outcome measure. RESULTS: Females tend to slightly outperform
      males on CIS, when other variables related to performance are taken into account.
      No evidence of an examinee and rater gender interaction effect was found.
      CONCLUSIONS: Results provide validity evidence supporting the interpretation and
      use of Step 2 CS CIS scores.

PMID- 21955762
TI  - A mixed-methods analysis of residents' written comments regarding their clinical
      supervisors.
AB  - BACKGROUND: Clinical faculty require feedback to guide their development.
      Although written comments submitted by residents on clinical teaching assessments
      (CTAs) are potentially a rich source of feedback, little is known about their
      information quality. METHOD: Naturalistic study involving thematic content
      analyses and concordancing of comments submitted in a sample of 1,601 CTAs.
      RESULTS: About half of the CTAs contained comments, and most were related to
      perceived teacher strengths. Mixed-methods analysis of comments in the "areas for
      improvement" field revealed that rather than offering constructive criticism,
      residents vocalized their perceived learning needs. Specific, behaviorally based
      comments were uncommon. CONCLUSIONS: In their present format, the written
      comments analyzed by this study seem unlikely to provide faculty with substantive
      feedback. Greater insight into residents' understanding of the CTA process,
      including motivational factors, is necessary if academic centers intend to
      maximize the formative value of CTAs.

PMID- 21955763
TI  - A comparison of performance evaluations of students on longitudinal integrated
      clerkships and rotation-based clerkships.
AB  - BACKGROUND: Longitudinal integrated clerkship (LIC) students typically perform as
      well as, if not better than, rotation-based clerkship (RBC) students on objective
      evaluations, yet few studies have compared performance in the clinical setting.
      This study compared in-training evaluation report (ITER) ratings of LIC and RBC
      students, including their correlation with more objective evaluations. METHOD: On
      the basis of prior academic performance, LIC students (n = 27) at Universities of
      Alberta, British Columbia, and Calgary were matched with four RBC students from
      their center. The authors compared reliability of ITER ratings, ITER ratings of
      clinical skills and professional attributes, and the correlation between ITER
      ratings and objective evaluations of clinical skills and professional attributes
      on the Medical Council of Canada Qualifying Examination (MCCQE) Part I. RESULTS:
      ITER ratings of LIC students were more reliable and significantly higher than
      those of RBC students for both clinical skills and professional attributes.
      However, LIC students had lower objective structured clinical examination scores
      and weaker correlations between subjective and objective evaluations of clinical
      skills. By comparison, LIC students scored higher on a particular component of
      the MCCQE and had stronger correlations between subjective and objective
      evaluations of professionalism. CONCLUSIONS: The discrepancy between ratings of
      LIC students' clinical skills on ITER and other evaluation formats may be due to
      differences between the content of training and objective evaluations, or
      systematic rater biases. Further studies are needed to confirm and explain these
      findings. Promisingly, our data suggest that the LIC model may allow for a more
      predictive evaluation of professional competencies.

PMID- 21955764
TI  - Competencies "plus": the nature of written comments on internal medicine
      residents' evaluation forms.
AB  - BACKGROUND: Comments on residents' in-training evaluation reports (ITERs) may be
      more useful than scores in identifying trainees in difficulty. However, little is
      known about the nature of comments written by internal medicine faculty on
      residents' ITERs. METHOD: Comments on 1,770 ITERs (from 180 residents in
      postgraduate years 1-3) were analyzed using constructivist grounded theory
      beginning with an existing framework. RESULTS: Ninety-three percent of ITERs
      contained comments, which were frequently easy to map onto traditional
      competencies, such as knowledge base (n = 1,075 comments) to the CanMEDs Medical
      Expert role. Many comments, however, could be linked to several overlapping
      competencies. Also common were comments completely unrelated to competencies, for
      instance, the resident's impact on staff (813), or personality issues (450).
      Residents' "trajectory" was a major theme (performance in relation to expected
      norms [494], improvement seen [286], or future predictions [286]). CONCLUSIONS:
      Faculty's assessments of residents are underpinned by factors related and
      unrelated to traditional competencies. Future evaluations should attempt to
      capture these holistic, integrated impressions.

PMID- 21955765
TI  - Using self-regulated learning theory to understand the beliefs, emotions, and
      behaviors of struggling medical students.
AB  - BACKGROUND: This study explored whether motivational, emotional, and behavioral
      aspects of self-regulated learning (SRL) are associated with academic performance
      in medical school. METHOD: Across two academic years (2008-2009 and 2009-2010),
      248 (73%) of 342 second-year students in an introductory clinical reasoning
      course completed surveys assessing 10 SRL constructs. Performance was
      operationalized as students' average grade on three course exams, and a tercile
      split was used to compare those in the lowest and highest third of achievement
      using a one-way multivariate analysis of variance. RESULTS: Findings revealed
      differences in the beliefs and emotions of the two extreme groups, F(10,136) =
      2.08, P = .03. Compared with high-performing students, low performers reported
      lower task value (Cohen d = -0.33) and self-efficacy beliefs (d = -0.33) as well
      as greater anxiety (d = 0.63), frustration (d = 0.54), and boredom (d = 0.44).
      CONCLUSIONS: Low-performing medical students in a clinical reasoning course
      demonstrated deficiencies in key SRL measures, providing insight for future,
      tailored remediation strategies.

PMID- 21955766
TI  - Does an emotional intelligence test correlate with traditional measures used to
      determine medical school admission?
AB  - BACKGROUND: As medical school admission committees are giving increased
      consideration to noncognitive measures, this study sought to determine how
      emotional intelligence (EI) scores relate to other traditional measures used in
      the admissions process. METHOD: EI was measured using an ability-based test
      (Mayer-Salovey-Caruso Emotional Intelligence Test, or MSCEIT) in two consecutive
      cohorts of medical school applicants (2006 and 2007) qualifying for the admission
      interview. Pearson correlations between EI scores and traditional measures (i.e.,
      weighted grade point average [wGPA], autobiographical sketch scores, and
      interview scores) were calculated. RESULTS: Of 659 applicants, 68% participated.
      MSCEIT scores did not correlate with traditional measures (r = -0.06 to 0.09, P >
      .05), with the exception of a small correlation with wGPA in the 2007 cohort (r =
      -0.13, P < .05). CONCLUSIONS: The lack of substantial relationships between EI
      scores and traditional medical school admission measures suggests that EI
      evaluates a construct fundamentally different from traits captured in our
      admission process.

PMID- 21955767
TI  - Relationship between medical student service and empathy.
AB  - BACKGROUND: Student participation in service activities during medical school is
      believed to enhance student professionalism and empathy. Yet, there are no
      studies that measure medical student empathy levels in relation to service
      activities. METHOD: Medical students from four classes (2007-2010) were surveyed
      at graduation using the Jefferson Scale of Physician Empathy-Student Version and
      questions about service activity during medical school. For two classes, empathy
      scores were also obtained at orientation. The data were analyzed using
      Statistical Package for the Social Sciences. Means comparison tests were
      performed. RESULTS: Mean empathy scores at graduation were higher for students
      who participated in service activities compared with those who reported no
      service (115.18 versus 107.97, P < .001). At orientation, students with no
      service had lower empathy scores, and those with any service had higher empathy
      scores. CONCLUSIONS: Student empathy and service activities during medical school
      are related. This may have implications for admissions committees.

PMID- 21955768
TI  - Exploring residents' perceptions of expertise and expert development.
AB  - BACKGROUND: Given the expectation that trainees develop into adaptive experts,
      able to effectively solve both routine and nonroutine problems of practice, and
      that they do so by actively guiding and shaping their own learning, the purpose
      of this study was to explore how residents at the postgraduate level of training
      conceptualize expertise, expert development, and their own learning in the
      developing expert trajectory. METHOD: This research was a grounded theory study
      conducted during an 11-month period at a large, urban, Canadian university.
      RESULTS: Three major themes were identified from the data analysis: (1) the
      dominance of routinization as the pathway to expert practice, (2) a sophisticated
      conceptualization of the role and complexity of routine practice, and (3) a
      recognition that nonroutine problems are an important part of physician practice.
      CONCLUSIONS: The results highlight our participants' emerging understanding of
      the complementary nature of routine and nonroutine problem solving by
      demonstrating their engagement in a process of progressive problem solving, as
      well as their inclusion of nonroutine problem solving as a crucial part of expert
      practice.

PMID- 21955769
TI  - Modern conceptions of elite medical practice among internal medicine faculty
      members.
AB  - BACKGROUND: To understand the modern conceptions of elite practice informing the
      hidden curriculum through use of peer nominations asking clinicians to identify
      exceptional practitioners. METHOD: We distributed a Web-based survey to
      Department of Medicine faculty at five universities in North America.
      Participants were asked to nominate individuals they deemed to be "outstanding
      practitioners" and to provide reasons. They were then asked to nominate
      "exceptional diagnosticians" and "exceptional professionals." RESULTS: Two
      hundred eighty-two physicians nominated 558 unique peers as "outstanding
      practitioners." Justifications included knowledge (45.1%), patient-related
      interpersonal skill (18.7%), teaching skill (10.8%), and research success (6.8%).
      More "exceptional diagnostician" nominees were nominated as "outstanding
      practitioners" (65.2%) relative to "exceptional professional" nominees (56.1%),
      although the effect size was small (phi = 0.09). CONCLUSIONS: Knowledge-based
      competencies maintain a central role in modern conceptions of elite medical
      practice, although, contrary to the historical dominance of biomedical abilities,
      a diverse set of skills and professional aptitudes are also well represented.

PMID- 21955770
TI  - F-type testlets and the effects of feedback and case-specificity.
AB  - BACKGROUND: A novel type of item sets, "f-type" testlets, was recently introduced
      on the United States Medical Licensing Examination. These testlets contain two or
      more questions associated with a common clinical scenario. In some cases, as the
      scenario unfolds, examinees are indirectly provided with feedback about their
      response to a testlet question. The effects of this format and of the provision
      of feedback to examinees about their performance are investigated. METHOD:
      Examinee behavior is predicted using an item response model, and observed
      examinee responses are compared with model expectations for f-type testlets. Mean
      model-data discrepancies among specific examinee groups are compared to study the
      dependencies across within-testlet items (i.e., case-specificity) and the impact
      of providing feedback. RESULTS: Findings showed that case-specificity effects
      were present (on average) for all examinee subgroups except examinees who both
      responded unsuccessfully to the initial item within an f-type testlet and
      received feedback. Case-specificity effects were negative for examinees who
      responded unsuccessfully to the initial testlet item but did not receive
      feedback. For those who responded successfully to the initial testlet items, case
      specificity effects were positive. CONCLUSIONS: Results suggest that responses to
      test questions within an f-type testlet are not independent-even after accounting
      for examinee proficiency and item characteristics. Case-specificity effects
      (i.e., dependencies) were observed on average for all examinees except those who
      both responded unsuccessfully to the initial item within an f-type testlet and
      received feedback. Research into modeling these effects through the use of more
      general item response models is recommended.

PMID- 21955771
TI  - What new residents do during their initial months of training.
AB  - BACKGROUND: Studies completed over the past decade suggest the presence of a gap
      between what students learn during medical school and their clinical
      responsibilities as first-year residents. The purpose of this survey was to
      verify on a large scale the responsibilities of residents during their initial
      months of training. METHOD: Practice analysis surveys were mailed in September
      2009 to 1,104 residency programs for distribution to an estimated 8,793 first
      year residents. Surveys were returned by 3,003 residents from 672 programs; 2,523
      surveys met inclusion criteria and were analyzed. RESULTS: New residents
      performed a wide range of activities, from routine but important communications
      (obtain informed consent) to complex procedures (thoracentesis), often without
      the attending physician present or otherwise involved. CONCLUSIONS: Medical
      school curricula and the content of competence assessments prior to residency
      should consider more thorough coverage of the complex knowledge and skills
      required early in residency.

PMID- 21955772
TI  - The relationship between direct observation, knowledge, and feedback: results of
      a national survey.
AB  - BACKGROUND: Multisource feedback can provide a comprehensive picture of a medical
      trainee's performance. The utility of a multisource feedback system could be
      undermined by lack of direct observation and accurate knowledge. METHOD: The
      National Board of Medical Examiners conducted a national survey of medical
      students, interns, residents, chief residents, and fellows to learn the extent to
      which certain behaviors were observed, to examine beliefs about knowledge of each
      other's performance, and to assess feedback. RESULTS: Increased direct
      observation is associated with the perception of more accurate knowledge, which
      is associated with increased feedback. Some evaluators provide feedback in the
      absence of accurate knowledge of a trainee's performance, and others who have
      accurate knowledge miss opportunities for feedback. CONCLUSIONS: Direct
      observation is a key component of an effective multisource feedback system.
      Medical educators and residency directors may be well advised to establish
      explicit criteria specifying a minimum number of observations for evaluations.

PMID- 21955773
TI  - Fatigue as impairment or educational necessity? Insights into surgical culture.
AB  - BACKGROUND: The authors examine fatigue culture among surgical residents and
      faculty members and whether it squares with recent, fatigue-focused Accreditation
      Council for Graduate Medical Education (ACGME) policies and educational
      initiatives. METHOD: Field observations of an academic general surgery program
      were supplemented with interviews (52 residents and 58 faculty members) conducted
      as part of a study of 15 general surgery programs. Field notes and interviews
      were analyzed for main themes. RESULTS: Most believe that fatigue surfaces after
      24 hours of work and has minor consequences. Surgeons believe that residents can
      learn to manage fatigue and that surgical practice requires that capacity. Proper
      training implies that residents experience fatigue, learn to perform capably and
      confidently while fatigued, and recognize their limits. CONCLUSIONS: Encountering
      and learning to manage fatigue are seen as educational necessities by surgeons, a
      view that runs counter to ACGME initiatives, requires reconsideration, and
      demands that attention be directed to professional and organizational practices
      that sustain fatigue culture.

PMID- 21955775
TI  - Who you know or what you know? Effect of examiner familiarity with residents on
      OSCE scores.
AB  - BACKGROUND: Despite the goal of objective structured clinical examinations
      (OSCEs) to be objective, examiner biases may influence scores. Examiner
      familiarity with candidates is a potential bias that has not been well studied.
      METHOD: To determine the effect of familiarity, OSCE scores for 158 internal
      medicine residents were analyzed by whether examiners were familiar with them,
      based on previous clinical encounters, and if previous impressions were positive
      or negative. A hierarchical multivariable analysis of variance was performed to
      control for resident, examiner, and level of training. RESULTS: Across 480
      interactions (50 examiners, 158 residents), multivariable analysis showed that
      positive familiarity was associated with a significant increase in ratings (+0.37
      on a 5-point scale), comparable to the difference between first- and third/fourth
      year residents. CONCLUSIONS: Familiarity with candidates is a significant source
      of examiner bias in OSCE scores. Consideration should be paid to the influence of
      examiners' previous knowledge of examinees and attempts made to mitigate this
      bias.

PMID- 21955776
TI  - In recognizing impending and uncertain change, we must remember that the
      underlying issues remain. Foreword.

PMID- 21955777
TI  - The Pseudomonas aeruginosa sensor RetS switches type III and type VI secretion
      via c-di-GMP signalling.
AB  - Acute bacterial infections are associated with motility and cytotoxicity via the
      type III secretion system (T3SS), while chronic infections are linked to biofilm
      formation and reduced virulence. In Pseudomonas aeruginosa, the transition
      between motility and sessility involves regulatory networks including the
      RetS/GacS sensors, as well as the second messenger c-di-GMP. The RetS/GacS
      signalling cascade converges on small RNAs, RsmY and RsmZ, which control a range
      of functions via RsmA. A retS mutation induces biofilm formation, and high levels
      of c-di-GMP produce a similar response. In this study, we connect RetS and c-di
      GMP pathways by showing that the retS mutant displays high levels of c-di-GMP.
      Furthermore, a retS mutation leads to repression of the T3SS, but also
      upregulates the type VI secretion system (T6SS), which is associated with chronic
      infections. Strikingly, production of the T3SS and T6SS can be switched by
      artificially modulating c-di-GMP levels. We show that the diguanylate cyclase
      WspR is specifically involved in the T3SS/T6SS switch and that RsmY and RsmZ are
      required for the c-di-GMP-dependent response. These results provide a firm link
      between the RetS/GacS and the c-di-GMP pathways, which coordinate bacterial
      lifestyles, as well as secretion systems that determine the infection strategy of
      P. aeruginosa.

PMID- 21955778
TI  - Experts by experience; the views of service user educators providing feedback on
      medical students' work based assessments.
AB  - Assessment tools were designed to provide health and social care students with
      multi-sourced, interprofessional feedback in practice. This includes feedback
      from service users. Third year medical students at the University of Leeds were
      given accesses to 4 assessment tools whilst in practice. Completed assessments
      were then sent to the university where service users and carers worked with
      university tutors to give further feedback and comment on the overall development
      of students. Three service users then took part in a focus group and one provided
      written feedback. Four key themes were identified from the focus group: *
      Preparation and support * The design of the tools * The process of using the
      tools in practice * Feedback. We found that the project provided both challenges
      and rewards for all involved. The service user educators involved were able to
      bring a different and valuable perspective to formative feedback. The combination
      of their personal and professional experiences, along with the preparation they
      had received, helped bridge the gap between service users in practice and
      university based tutors. The findings from this study went on to inform a review
      of the assessment tools and revised versions are now being used.

PMID- 21955779
TI  - High temperature normal phase liquid chromatography of aromatic hydrocarbons on
      bare zirconia.
AB  - The normal phase HPLC behavior of a bare zirconia column was studied at
      temperatures up to 200  degrees C using a hexane mobile phase. The use of
      elevated column temperatures significantly decreased the retention of twenty five
      aromatic model compounds according to the van't Hoff equation (>30-fold decrease
      for some compounds). Large improvements in peak shape, efficiency (>2.2-fold),
      aromatic group-type selectivity, and column re-equilibration times (>5-fold) were
      obtained at elevated temperatures. The thermal decomposition of two polar
      nitrogen compounds (indole and carbazole) was observed in a
      hexane/dichloromethane mobile phase at temperatures greater than 100  degrees C.
      The first order decomposition of carbazole was studied in further detail.

PMID- 21955780
TI  - Adsorption kinetics of deamidated antibody variants on macroporous and dextran
      grafted cation exchangers. III. Microscopic studies.
AB  - The kinetics of single and multicomponent adsorption of deamidated monoclonal
      antibody (mAb) charge variants is investigated using confocal laser scanning
      microscopy for two commercial cation exchangers, one with an open macroporous
      structure--UNOsphere S--and the other with charged dextran grafts--Capto S.
      Markedly different intraparticle concentration profiles are obtained, being very
      sharp for UNOsphere S, indicating pore diffusion control, but much more diffuse
      for Capto S, consistent with a solid or surface diffusion mechanism. For single
      component adsorption, the mAb effective pore diffusivities for UNOsphere S are
      approximately D(e)=4.5*10(-8) and 8.3*10(-8) cm(2)/s at pH 5 and 7.5,
      respectively, while effective solid diffusivities for Capto S are D(s)=0.98*10(
      9) and 5.0*10(-9) cm(2)/s at pH 5 and 7.5, respectively. Two-component adsorption
      at pH 7.5, where the deamidated variants are bound selectively also showed
      markedly different profiles for the two matrices. UNOsphere S showed distinct
      adsorption zones within the particles indicating that multicomponent transport
      occurs with continuous displacement of the more deamidated variant by the less
      deamidated one. Capto S, however, showed no spatial resolution of the variants
      within the particle during co-adsorption and very slow mass transfer during
      sequential adsorption suggesting that protein counter-diffusion is severely
      hindered in this material.

PMID- 21955781
TI  - Use of an accurate-mass database for the systematic identification of
      transformation products of organic contaminants in wastewater effluents.
AB  - In this article, a systematic approach is proposed to assist and simplify the
      identification of transformation products (TPs) of organic contaminants. This
      approach is based on the use of characteristic fragmentation undergone by organic
      contaminants during MS/MS fragmentation events, and the relationship and
      consistency with the transformations experimented by these chemicals in the
      environment or during water treatment processes. With this in mind, a database
      containing accurate-mass information of 147 compounds and their main fragments
      generated by CID MS/MS fragmentation experiments was created using an LC-QTOF
      MS/MS system. The developed database was applied to the identification of
      tentative TPs and related unexpected compounds in eight wastewater effluent
      samples. The approach comprises basically three stages: (a) automatic screening,
      (b) identification of possible TPs and (c) confirmation by MS/MS analysis.
      Parameters related to the search of compounds in the database have been optimized
      and their dependence with the exhaustiveness of the study evaluated. Eight
      degradation products, from the pharmaceuticals acetaminophen, amoxicillin,
      carbamazepine, erythromycin and azithromycin and from the pesticide diazinon,
      were identified with a high grade of accuracy. Three of them were confirmed by
      analysis of the corresponding analytical standards.

PMID- 21955782
TI  - Determination of accessible silanols groups on silica gel surfaces using
      microcalorimetric measurements.
AB  - The calorimetric measurements of methanol and hexane heats of immersion were
      carried out on different silica gels. Based on the difference in immersion heats,
      a methodology for the determination of the number of silanols on the surface is
      presented. The calculated concentration of residual silanols on the silica gel
      surface agreed with data found in the literature. The proposed methodology, based
      on a calculation of possible hydrogen bond formation, was also tested on the
      series of bonded stationary phases with different coverage densities. A very good
      correlation between the calculated number of accessible residual silanols and the
      coverage density of bonded ligands was observed.

PMID- 21955783
TI  - Government regulation to promote healthy food environments--a view from inside
      state governments.
AB  - Food policy interventions are an important component of obesity-prevention
      strategies and can potentially drive positive changes in obesogenic environments.
      This study sought to identify regulatory interventions targeting the food
      environment, and barriers/facilitators to their implementation at the Australian
      state government level. In-depth interviews were conducted with senior
      representatives from state/territory governments, statutory authorities and non
      government organizations (n =45) to examine participants' (i) suggestions for
      regulatory interventions for healthier food environments and (ii) support for pre
      selected regulatory interventions derived from a literature review. Data were
      analysed using thematic and constant comparative analyses. Interventions commonly
      suggested by participants were regulating unhealthy food marketing; limiting the
      density of fast food outlets; pricing reforms to decrease fruit/vegetable prices
      and increase unhealthy food prices; and improved food labelling. The most
      commonly supported pre-selected interventions were related to food marketing and
      service. Primary production and retail sector interventions were least supported.
      The dominant themes were the need for whole-of-government and collaborative
      approaches; the influence of the food industry; conflicting policies/agenda;
      regulatory challenges; the need for evidence of effectiveness; and economic
      disincentives. While interventions such as public sector healthy food service
      policies were supported by participants, marketing restrictions and fiscal
      interventions face substantial barriers including a push for deregulation and
      private sector opposition.

PMID- 21955784
TI  - Abstracts of the 1st Congress of the International Academy of Digital Pathology,
      August 3-5, 2011, Quebec City, Canada.

PMID- 21955788
TI  - Identifying Tmem59 related gene regulatory network of mouse neural stem cell from
      a compendium of expression profiles.
AB  - BACKGROUND: Neural stem cells offer potential treatment for neurodegenerative
      disorders, such like Alzheimer's disease (AD). While much progress has been made
      in understanding neural stem cell function, a precise description of the
      molecular mechanisms regulating neural stem cells is not yet established. This
      lack of knowledge is a major barrier holding back the discovery of therapeutic
      uses of neural stem cells. In this paper, the regulatory mechanism of mouse
      neural stem cell (NSC) differentiation by tmem59 is explored on the genome-level.
      RESULTS: We identified regulators of tmem59 during the differentiation of mouse
      NSCs from a compendium of expression profiles. Based on the microarray
      experiment, we developed the parallelized SWNI algorithm to reconstruct gene
      regulatory networks of mouse neural stem cells. From the inferred tmem59 related
      gene network including 36 genes, pou6f1 was identified to regulate tmem59
      significantly and might play an important role in the differentiation of NSCs in
      mouse brain. There are four pathways shown in the gene network, indicating that
      tmem59 locates in the downstream of the signalling pathway. The real-time RT-PCR
      results shown that the over-expression of pou6f1 could significantly up-regulate
      tmem59 expression in C17.2 NSC line. 16 out of 36 predicted genes in our
      constructed network have been reported to be AD-related, including Ace, aqp1,
      arrdc3, cd14, cd59a, cds1, cldn1, cox8b, defb11, folr1, gdi2, mmp3, mgp, myrip,
      Ripk4, rnd3, and sncg. The localization of tmem59 related genes and functional
      related gene groups based on the Gene Ontology (GO) annotation was also
      identified. CONCLUSIONS: Our findings suggest that the expression of tmem59 is an
      important factor contributing to AD. The parallelized SWNI algorithm increased
      the efficiency of network reconstruction significantly. This study enables us to
      highlight novel genes that may be involved in NSC differentiation and provides a
      shortcut to identifying genes for AD.

PMID- 21955789
TI  - Mulcom: a multiple comparison statistical test for microarray data in
      Bioconductor.
AB  - BACKGROUND: Many microarray experiments search for genes with differential
      expression between a common "reference" group and multiple "test" groups. In such
      cases currently employed statistical approaches based on t-tests or close
      derivatives have limited efficacy, mainly because estimation of the standard
      error is done on only two groups at a time. Alternative approaches based on ANOVA
      correctly capture within-group variance from all the groups, but then do not
      confront single test groups with the reference. Ideally, a t-test better suited
      for this type of data would compare each test group with the reference, but use
      within-group variance calculated from all the groups. RESULTS: We implemented an
      R-Bioconductor package named Mulcom, with a statistical test derived from the
      Dunnett's t-test, designed to compare multiple test groups individually against a
      common reference. Interestingly, the Dunnett's test uses for the denominator of
      each comparison a within-group standard error aggregated from all the
      experimental groups. In addition to the basic Dunnett's t value, the package
      includes an optional minimal fold-change threshold, m. Due to the automated,
      permutation-based estimation of False Discovery Rate (FDR), the package also
      permits fast optimization of the test, to obtain the maximum number of
      significant genes at a given FDR value. When applied to a time-course experiment
      profiled in parallel on two microarray platforms, and compared with two commonly
      used tests, Mulcom displayed better concordance of significant genes in the two
      array platforms (39% vs. 26% or 15%), and higher enrichment in functional
      annotation to categories related to the biology of the experiment (p value <
      0.001 in 4 categories vs. 3). CONCLUSIONS: The Mulcom package provides a powerful
      tool for the identification of differentially expressed genes when several
      experimental conditions are compared against a common reference. The results of
      the practical example presented here show that lists of differentially expressed
      genes generated by Mulcom are particularly consistent across microarray platforms
      and enriched in genes belonging to functionally significant groups.

PMID- 21955790
TI  - One-pot enzymatic production of 2-acetamido-2-deoxy-D-galactose (GalNAc) from 2
      acetamido-2-deoxy-D-glucose (GlcNAc).
AB  - 2-Acetamido-2-deoxy-D-galactose (GalNAc) is a common monosaccharide found in
      biologically functional sugar chains, but its availability is often limited due
      to the lack of abundant natural sources. In order to produce GalNAc from
      abundantly available sugars, 2-acetamido-2-deoxy-D-glucose (GlcNAc) was converted
      to GalNAc by a one-pot reaction using three enzymes involved in the galacto-N
      biose/lacto-N-biose I pathway of bifidobacteria. Starting the reaction with 600
      mM GlcNAc, 170 mM GalNAc was produced at equilibrium in the presence of catalytic
      amounts of ATP and UDP-Glc under optimized conditions. GalNAc was separated from
      GlcNAc using water-eluting cation-exchange chromatography with a commonly
      available cation-exchange resin.

PMID- 21955791
TI  - Patient preferences and willingness to pay for arthroplasty surgery in patients
      with osteoarthritis of the hip.
AB  - Little is known about the economic value patients place on effective treatment of
      osteoarthritis (OA) of the hip. The purpose of this study was to evaluate the
      value of total hip arthroplasty (THA) and hip resurfacing arthroplasty (HRA) to
      patients with advanced hip OA by measuring their preferences and willingness to
      pay (WTP) for either procedure. Seventy-three patients younger than 65 years with
      advanced hip OA reviewed information about the risks and benefits of THA and HRA
      and were asked which procedure they would choose and how much they would be
      willing to pay for it. Sixty-nine percent of patients chose THA (average WTP, $69
      419) and 31% chose HRA (average WTP, $83 195). There was no correlation between
      WTP and annual income or total assets. However, patients with modest income and
      assets could have reported that they were willing and able to pay more than they
      could actually afford, and WTP dropped and correlation with income rose if we
      excluded high responses from the poorest respondents. These results may have
      important policy implications as patients are asked to share a greater burden of
      the cost of their care for chronic conditions such as OA.

PMID- 21955792
TI  - Pseudotumor in a well-fixed metal-on-polyethylene uncemented hip arthroplasty.
AB  - The incidence of pseudotumor formation has been reported to be 1% in patients
      with metal-on-metal resurfacing arthroplasties. This complication is not
      exclusive to these patients. We report a case of pseudotumor formation secondary
      to femoral head-neck corrosion after a metal-on-polyethylene uncemented total hip
      arthroplasty.

PMID- 21955793
TI  - Midterm results of femoral impaction bone grafting with an allograft combined
      with hydroxyapatite in revision total hip arthroplasty.
AB  - The purpose of this study was to evaluate the outcome of femoral impaction bone
      grafting with an allograft combined with hydroxyapatite (HA). Fifty-four
      consecutive femoral reconstructions that were performed with the use of frozen
      morselized allografts and HA were followed up retrospectively. The average follow
      up period was 92 months. A femoral head and HA were mixed and used as allograft.
      The average Merle d'Aubigne clinical score improved from 8.9 preoperatively to
      13.1 points postoperatively. Stem subsidence was seen in 26 hips; however, it was
      not progressive after 1 year postoperatively. Cortical repair was detected at an
      average of 7 months postoperatively. Impaction bone grafting with an allograft
      combined with HA provided favorable results, with bone remodeling and less
      subsidence.

PMID- 21955794
TI  - Symmetry breaking and the establishment of cell polarity in budding yeast.
AB  - Cell polarity is typically oriented by external cues such as cell-cell contacts,
      chemoattractants, or morphogen gradients. In the absence of such cues, however,
      many cells can spontaneously polarize in a random direction, suggesting the
      existence of an internal polarity-generating mechanism whose direction can be
      spatially biased by external cues. Spontaneous 'symmetry-breaking' polarization
      is likely to involve an autocatalytic process set off by small random
      fluctuations. Here we review recent work on the nature of the autocatalytic
      process in budding yeast and on the question of why polarized cells only develop
      a single 'front'.

PMID- 21955795
TI  - Cell flow and tissue polarity patterns.
AB  - Planar tissue polarity is a fundamental feature of many epithelia. Large-scale
      cell polarity patterns govern the orientation of external structures such as
      hairs and cilia. Tissue polarity patterns arise from the collective organization
      of cells, which are polarized individually. Such cell and tissue polarities are
      reflected in anisotropic distributions of proteins of the planar cell polarity
      (PCP) pathway. Here we give an overview on recent progress in understanding how
      large-scale patterns of tissue polarity are controlled. We highlight the role of
      active mechanical events in the organization of polarity patterns during the
      development of the pupal fly wing. Patterns of cell flow are generated by
      mechanical stresses exerted on the tissue as well as by oriented cell divisions
      and neighbor exchanges. We discuss how the resulting tissue shear controls
      polarity orientation. We argue that the often-observed alignment of PCP either
      parallel or perpendicular to the long axis of developing tissues is a
      characteristic consequence of shear-induced polarity alignment. This principle
      allows for the versatile and robust generation of polarity patterns in tissues.

PMID- 21955796
TI  - New directions in coral reef microbial ecology.
AB  - Microbial processes largely control the health and resilience of coral reef
      ecosystems, and new technologies have led to an exciting wave of discovery
      regarding the mechanisms by which microbial communities support the functioning
      of these incredibly diverse and valuable systems. There are three questions at
      the forefront of discovery: What mechanisms underlie coral reef health and
      resilience? How do environmental and anthropogenic pressures affect ecosystem
      function? What is the ecology of microbial diseases of corals? The goal is to
      understand the functioning of coral reefs as integrated systems from microbes and
      molecules to regional and ocean-basin scale ecosystems to enable accurate
      predictions of resilience and responses to perturbations such as climate change
      and eutrophication. This review outlines recent discoveries regarding the
      microbial ecology of different microenvironments within coral ecosystems, and
      highlights research directions that take advantage of new technologies to build a
      quantitative and mechanistic understanding of how coral health is connected
      through microbial processes to its surrounding environment. The time is ripe for
      natural resource managers and microbial ecologists to work together to create an
      integrated understanding of coral reef functioning. In the context of long-term
      survival and conservation of reefs, the need for this work is immediate.

PMID- 21955798
TI  - Follow-up of patients undergoing both semiquantitated immunochemical fecal occult
      blood and colonoscopy examinations.
AB  - The semiquantitated immunochemical fecal occult blood test (I-FOBT) used for
      colorectal cancer (CRC) screening has had its long-term performance
      characteristics determined by clinical follow-up or sometimes by colonoscopy as
      the 'gold standard'. We reanalyzed a file of total colonoscopy patients who also
      prepared three I-FOBTs, processed by the OC-MICRO instrument, using at least 50
      ng Hb/ml buffer threshold to determine a positive test. The performance of both
      tests was evaluated by the National Cancer Registry follow-up to identify new
      CRCs and by determining the effects of the number of tests prepared and their
      thresholds for analysis, sex, and age on results. A total of 1630 patients, mean
      age 62.7 years, SD 11.9, 50.1% men, having undergone both tests were followed up
      for a mean of 51.5 months, SD 13.4; 25 CRC patients were registered. At 36
      months, I-FOBT sensitivity for CRC was 95.8% (95% confidence interval 87.8, 104),
      as was initial colonoscopy; within 48 months, it was 92% (95% confidence interval
      81.4, 103) and 96%, respectively. I-FOBT identified 70 of the 122 (57.2%)
      colonoscopy-detected advanced adenoma patients. CRC and advanced adenomatous
      polyps were more common in men (P<0.01), whose risk increased at 51-73 years
      (odds ratio 4.639, P=0.056), but not among women (odds ratio 1.952). It then
      increased significantly (P<0.01) for both sexes aged at least 74 years. I-FOBTs
      identified most CRCs diagnosed within 36 months of follow-up with sensitivity
      similar to that of initial colonoscopy, with neither test identifying every CRC
      patient. Sex and age influence results and need consideration when planning
      population screening.

PMID- 21955797
TI  - Environmental constraints defining the distribution, composition, and evolution
      of chlorophototrophs in thermal features of Yellowstone National Park.
AB  - Chlorophotoautotrophy, the use of chlorophylls to convert light energy into
      chemical energy for carbon dioxide fixation, is the primary metabolic process
      linking the inorganic and organic carbon pools on Earth. To understand the
      potential effects of various environmental constraints on the evolution of
      chlorophototrophy better, we studied the distribution, diversity, and abundance
      of chlorophylls and genes involved in their synthesis along geothermal gradients
      in Yellowstone National Park, Wyoming. Genes involved in chlorophyll biosynthesis
      were constrained to temperatures of less than ~70  degrees C and were only
      detected at this elevated temperature when the pH was in the circumneutral to
      alkaline range. The upper temperature limit for the detection of chlL/bchL(1) and
      bchY(2) decreased systematically with increasingly acidic pH, an observation
      likely attributable to sulfide, which upon oxidation, generates acidic spring
      water and reduces the availability of bicarbonate the preferred source of
      inorganic carbon for phototrophs. Spring pH was also the best predictor of the
      phylogenetic diversity of chlL/bchL communities. The phylogenetic similarity of
      chlL/bchL genes between sites was significantly correlated with that of
      chlorophylls. The predominance of chlorophyll a and bacteriochlorophyll a among
      extracted pigments was consistent with predominance of chlL/bchL genes affiliated
      with the Cyanobacteria and Chloroflexiales, respectively, and might be related to
      the fact that the majority of these organisms are photoautotrophs. Together,
      these results suggest that a combination of temperature, pH, and/or sulfide
      influences the distribution, diversity, and evolution of chlorophotrophs and the
      chlorophylls that they synthesize.

PMID- 21955799
TI  - Geographical patterns of Kaposi's sarcoma, nonHodgkin lymphomas, and cervical
      cancer associated with HIV infection in five African populations.
AB  - The objective of this study is to describe the most recent geographical patterns
      of incidence of AIDS-related cancers, Kaposi's sarcoma (KS), nonHodgkin lymphoma
      (NHL), and cervical cancer in North African and subSaharan African populations.
      Data were extracted for the period 1998-2002 from five African population-based
      cancer registries: Kyadondo, Harare, Setif, Sousse, and Gharbiah. Age
      standardized rates were calculated using the African standard population; a
      comparison was made between these populations by computing the standardized
      incidence ratio and 95% confidence intervals. The KS rate was found to be
      significantly higher in men than in women, and higher in Harare (women:
      26.3/100,000; men: 50.4/100,000) and Kyadondo (women: 23.6/100,000; men:
      30.2/100,000) than in the North African sites for both sexes (<0.3/100,000). In
      addition, the KS rate in women from Harare was similar to that for Kyadondo.
      Gharbiah presented the highest rates for NHL (women: 7 per 100,000; men:
      11.9/100,000) for both sexes. We observed that Harare and Kyadondo had similar
      age-specific incidence in the high-risk age group for HIV/AIDS (15-49 years), and
      these rates were 4.5-fold higher in subSaharan populations than those in the
      North African sites. Thus, it was observed that the pattern of HIV prevalence is
      variable with the lowest prevalence in North African countries, intermediate
      prevalence in Uganda, and the highest prevalence in Zimbabwe. Our findings show
      that the incidence of NHL and cervical cancer, considered to be HIV/AIDS-related
      cancers, does not follow the pattern of HIV prevalence in the five studied
      African populations. Thus, the highest NHL incidence rate in both sexes in Gambia
      may be explained, at least in great part, by the highest hepatitis C virus
      prevalence observed there. Indeed, factors other than HIV infection likely
      contribute to their geographical patterns.

PMID- 21955800
TI  - The polymorphism of the CHRNA5 gene and the strength of nicotine addiction in
      lung cancer and COPD patients.
AB  - A rare variant of chromosomal region 15q25.1, marked by rs16969968 (substitution
      1354G>A in CHRNA5), was found to be associated with increased lung cancer and
      nicotine-dependence risk. We attempted to confirm the relationship of the
      polymorphism of the CHRNA5 gene and nicotine-dependence strength measured by the
      Fagerstrom test with the serum cotinine level in lung cancer and chronic
      obstructive pulmonary disease (COPD) patients and healthy individuals.
      Polymorphism of the CHRNA5 gene was analyzed using the PCR-based restriction
      fragment length polymorphism method in 97 lung cancer patients, 99 COPD patients,
      and 98 healthy individuals. The Fagerstrom test was used as an instrument for
      assessing the intensity of physical addiction. Cotinine serum level was measured
      using an enzyme-linked immunosorbent assay. The frequencies of AA, AG, and GG
      genotypes were 10.5, 47.3, and 42.2%, respectively. The polymorphism of CHRNA5
      did not have a significant influence on the elevated risk of lung cancer and
      COPD. The percentage of smokers did not differ between groups of study
      participants with different genotypes. However, the presence of the GG genotype
      decreased the risk of nicotine addiction strength (hazard ratio=0.238; 95%
      confidence interval 0.066-0.857; P<0.05). Moreover, allele A was presented more
      frequently in participants with a high level of nicotine dependence and in
      participants with early addiction onset (P<0.05). Serum cotinine level was
      significantly correlated with the results of the Fagerstrom test (P<0.001). The
      carriers of allele A expressed significantly higher levels of cotinine when
      compared with the carriers of the GG genotype (P=0.05). We report for the first
      time the relationship between the polymorphism of the CHRNA5 gene and the
      strength of nicotine addiction measured by multiple factors including the
      Fagerstrom test score.

PMID- 21955801
TI  - Polydiacetylene-supported silica films formed at the air/water interface.
AB  - Mesostructured silica films have attracted interest as potential platforms for
      sensing, molecular sieving, catalysis, and others. The fabrication of free
      standing silica films on water, however, is challenging due to the need for
      scaffolding agents that would constitute effective templates. We describe the
      assembly of thin film at the air/water interface comprising quaternary silicates
      and polydiacetylene (PDA), a unique chromatic polymer forming two-dimensional
      conjugated networks, and the use of these films for biological sensing. PDA
      exhibits a dual role in the system-both as the amphiphilic matrix facilitating
      immobilization of the silicate colloidal units at the air/water interface and
      additionally a chromatic reporter that undergoes visible blue-red transitions,
      accompanied by fluorescence transformations, in the presence of analytes. We
      demonstrate the application of the silicate/PDA thin films for the detection of
      bacterial proliferation.

PMID- 21955802
TI  - In situ preparation of Al-containing PVDF ultrafiltration membrane via sol-gel
      process.
AB  - Recently, inorganic nanoparticles blended within polymeric membranes have shown
      improved antifouling performance in wastewater treatment. However, agglomeration
      of nanoparticles remains as one of the major obstacles for generating a uniform
      surface. In this study, a new method for in situ preparation of Al-containing
      PVDF ultrafiltration membranes to improve the dispersion of nanoparticles is
      reported. The strategy of this method is to combine sol-gel process with
      traditional immersion precipitation process. Al sol was synthesized by the
      addition of anionic exchange resin in N,N-dimethylformamide (DMF) solvent
      containing aluminum chloride. Homogeneous Al-containing PVDF casting solution was
      then obtained by dissolving PVDF polymer in the Al sol. The membrane formation
      mechanism was investigated by precipitation kinetics and morphology. Results
      indicate that the addition of Al species can accelerate phase inversion of
      casting solution. Scanning electron microscopic images show that a typical
      transition from sponge-like structure to finger-like structure occurred with
      increasing Al species content. The existence and dispersion states of Al species
      in the resultant membrane matrix were further examined by transmission electron
      microscope and X-ray photoelectron spectrometer. The results indicate the Al
      species nanoparticles were well dispersed throughout PVDF matrix. Dynamic BSA
      fouling resistance experiments demonstrate the Al-containing PVDF membranes
      possess improved separation performances over the pure PVDF membranes.

PMID- 21955803
TI  - Immiscible surfactant droplets on thin liquid films: spreading dynamics, subphase
      expulsion and oscillatory instabilities.
AB  - After deposition of immiscible, surface-active liquids on thin liquid films of
      higher surface tension, Marangoni stresses thin the liquid film around the
      surfactant droplet and induce a radially outward flow. We observed an oscillatory
      instability, caused by temporary trapping and subsequent release of subphase
      liquid from underneath the surfactant droplet. Height profiles of the thin liquid
      films were monitored using optical interferometry and fluorescence microscopy,
      both in the vicinity of the deposited surfactant droplet and at larger distances.
      Numerical calculations based on the lubrication approximation are compared to the
      experimental results. Good agreement between the experimental and calculated far
      field dynamics and values of the spreading exponents was found.

PMID- 21955804
TI  - Effective detection of rare variants in pooled DNA samples using Cross-pool
      tailcurve analysis.
AB  - Sequencing targeted DNA regions in large samples is necessary to discover the
      full spectrum of rare variants. We report an effective Illumina sequencing
      strategy utilizing pooled samples with novel quality (Srfim) and filtering
      (SERVIC4E) algorithms. We sequenced 24 exons in two cohorts of 480 samples each,
      identifying 47 coding variants, including 30 present once per cohort. Validation
      by Sanger sequencing revealed an excellent combination of sensitivity and
      specificity for variant detection in pooled samples of both cohorts as compared
      to publicly available algorithms.

PMID- 21955805
TI  - A new minimal deleted region at 11q22.3 reveals the importance of interpretation
      of diminished FISH signals and the choice of probe for ATM deletion screening in
      chronic lymphocytic leukemia.
AB  - Deletion of ATM detected by fluorescent in situ hybridization (FISH) in chronic
      lymphocytic leukemia predicts short treatment free survival and poor outcome
      following alkylator/purine analogue therapy. We describe five cases, with a
      diminished ATM FISH signal, investigated by TP53 mutation/dysfunction studies and
      single nucleotide polymorphism (SNP) array. The diminished signal represented
      loss of the ATM gene, which could have been missed were the cases not further
      investigated. These rare cases highlight the need for careful consideration of
      the choice of probe and interpretation of unusual signal patterns in FISH
      screening. We define a new minimal region of deletion at 11q22.3.

PMID- 21955806
TI  - Is there any advantage to combined trastuzumab and chemotherapy in perioperative
      setting her 2neu positive localized gastric adenocarcinoma?
AB  - We report here a 44-year-old Moroccan man with resectable gastric adenocarcinoma
      with overexpression of human epidermal growth factor receptor 2 (HER2) by
      immunohistochemistry who was treated with trastuzumab in combination with
      chemotherapy in perioperative setting. He received 3 cycles of neoadjuvant
      chemotherapy consisting of trastuzumab, oxaliplatin, and capecitabine.
      Afterwards, he received total gastrectomy with extended D2 lymphadenectomy
      without spleno-pancreatectomy. A pathologic complete response was obtained with a
      combination of trastuzumab and oxaliplatin and capecitabine. He received 3 more
      cycles of trastuzumab containing regimen postoperatively.We conclude that
      resectable gastric carcinoma with overexpression of the c-erbB-2 protein should
      ideally be managed with perioperative combination of trastuzumab with
      chemotherapy. Further research to evaluate trastuzumab in combination with
      chemotherapy regimens in the perioperative and adjuvant setting is urgently
      needed.

PMID- 21955807
TI  - Self-reported responses to medication therapy management services for older
      adults: analysis of a 5-year program.
AB  - BACKGROUND: Medication therapy management (MTM) services provide essential
      reviews of drug regimens and are increasingly recognized as beneficial to patient
      safety, improved health outcomes, and cost savings. OBJECTIVE: To assess patient
      behavioral outcomes from an MTM service, including actions following receipt of a
      pharmacist report. METHODS: A retrospective analysis of an MTM program at the
      Sanford Center for Aging (NV, USA) was conducted. Outcome measures included
      whether the patient discussed the review with the physician, whether any changes
      in the client's drug regimen occurred, and whether the client feels more
      knowledgeable about his or her medications. Predictor variables included basic
      demographics, prescription insurance status, number of prescriptions taken, self
      reported health status, and use of medications considered to be high risk. The
      analysis plan involved the use of multivariate logistic regression models.
      RESULTS: The odds of discussing the medication review with physicians, making
      changes recommended in the report, and both discussing and making a change were
      65%, 60%, and 67%, respectively, lower among those below poverty level than among
      those above poverty level; 95% confidence intervals (CIs): 0.15, 0.80; 0.18,
      0.85; and 0.15, 0.73, respectively. The odds of those using high-risk drugs of
      making changes in drug regimens, and of discussing with physicians and making
      changes together, were 2 times higher than the odds of those not using these
      drugs, 95% CIs: 1.02, 4.31 and 1.20, 4.87, respectively. The likelihood of those
      reporting good or excellent health of doing the combination of discussing the MTM
      report with physicians and to make a drug regimen change was 2 times greater than
      for those reporting poor to fair health, 95% CI: 1.08, 3.65. Gender, ethnicity,
      age group, rural status, prescription drug insurance, and high polypharmacy were
      not significant factors for acting on the medication review in the adjusted
      model. CONCLUSION: MTM services are associated with enhanced patient self
      advocacy, but like other interventions, they are constrained by social
      disparities. Greater attention to the resources of target populations to respond
      to pharmacy services is merited.

PMID- 21955809
TI  - Challenges to counseling customers at the pharmacy counter--why do they exist?
AB  - Challenges to engage pharmacy customers in medicine dialogues at the counter have
      been identified comprising a new and extended clinical role for pharmacists in
      the health care system. This article seeks to expand understanding of factors
      involved in successful interaction at the pharmacy counter between customers and
      pharmacy staff to develop their relationship further. Practical challenges to
      customer encounters experienced by community pharmacists are discussed using
      theory from the field of mainly inter-relational communication and particular
      studies on pharmacy communication. Preconceived expectation of customers, the
      type of question asked by pharmacy staff, and differences in perception of
      illness and medicines between staff and customers are discussed. Both staff and
      customer influence the outcome of attempts by pharmacy staff to engage customers
      in dialogue about their medicine use through a complex mechanism of interaction.
      It is recommended that practitioners and researchers begin to distinguish, both
      theoretically and practically, between the content of a conversation and the
      underlying relationship when exploring and further developing the therapeutic
      relationship between pharmacy personnel and customers.

PMID- 21955808
TI  - The association of race, comorbid anxiety, and antidepressant adherence among
      Medicaid enrollees with major depressive disorder.
AB  - BACKGROUND: Depressed patients often have comorbid anxiety. African-Americans
      with depression are less likely to adhere to antidepressant treatment. Knowledge
      of the association between race, comorbid anxiety, and adherence among Medicaid
      enrollees with depression is limited. OBJECTIVE: The objective of this study was
      to evaluate the association of race, comorbid anxiety, and antidepressant
      adherence, and persistence among Medicaid enrollees with major depressive
      disorder (MDD). METHODS: The MarketScan Multi-State Medicaid Database (Thomson
      Reuters, Ann Arbor, MI) was used in this retrospective cross-sectional study.
      Medicaid enrollees aged between 18 and 64 years, with MDD but without bipolar
      disorders, and with a newly initiated antidepressant between January 1, 2004 and
      December 31, 2006 were identified. An index date was assigned corresponding to
      the newly initiated antidepressant. Patients having claims for any antidepressant
      refills during the 12 months before the index date were excluded. Eligible
      patients were then followed-up for 12 months after the index date. Adherence was
      measured by a modified medication possession ratio. Adherence was evaluated using
      multivariate logistic regression. Persistence was assessed based on treatment
      discontinuation and examined by Kaplan-Meier survival curves and Cox
      propositional hazard regression models. RESULTS: A total of 3083 Medicaid
      patients with MDD were included. Approximately, 25% of patients had comorbid
      anxiety. The odds of adhering to antidepressants were 40% lower among African
      Americans than Caucasians, adjusting for covariates (AOR [adjust odds
      ratio]=0.60; 95% confidence interval [CI]=0.51-0.72, P<.001). MDD patients with
      comorbid anxiety were more likely to adhere to antidepressants than patients with
      MDD alone (AOR=1.55, 95% CI=1.27-1.90, P<.001). African-Americans had a higher
      hazard of not persistently taking antidepressants (hazard ratio=1.47, 95% CI=1.30
      1.65, P<.001). The interaction between race and comorbid anxiety was not
      associated with adherence or persistence. CONCLUSIONS: Among Medicaid enrollees
      with MDD, race and comorbid anxiety disorders are significantly associated with
      antidepressant adherence and persistence. Physicians need to recognize comorbid
      anxiety and race as 2 important determinants of antidepressant use behaviors when
      they encounter Medicaid patients with MDD.

PMID- 21955810
TI  - Postcode lotteries in public health--the NHS Health Checks Programme in North
      West London.
AB  - BACKGROUND: Postcode lotteries in health refer to differences in health care
      between different geographic areas. These have been previously associated with
      clinical services. However there has been little documentation of postcode
      lotteries relating to preventative health care services. This paper describes a
      postcode lottery effect in relation to the NHS Health Checks Programme (a
      national cardiovascular screening programme in England) in eight PCTs in the
      North West sector of London. METHODS: A descriptive cross-sectional analysis of
      the Health Checks Programme was carried out in eight PCTs in North West London
      using a structured data-collecting instrument. RESULTS: The analysis found
      variation in the implementation of the national Health Checks Programme in terms
      of: the screening approach taken; the allocated budget (which varied from L69,000
      to L1.4 million per 100,000 eligible population); payment rates made to providers
      of Health Checks; tools used to identify and measure risk of cardiovascular
      disease and diabetes; monitoring and evaluation; and preventative services
      available following the health check. CONCLUSIONS: This study identifies a
      postcode lottery effect related to a national public health programme. Although
      it is important to allow enough flexibility in the design of the Health Checks
      Programme so that it fits in with local factors, aspects of the programme may
      benefit from greater standardisation or stronger national guidance.

PMID- 21955812
TI  - Extra virgin olive oil improves learning and memory in SAMP8 mice.
AB  - Polyphenols are potent antioxidants found in extra virgin olive oil (EVOO);
      antioxidants have been shown to reverse age- and disease-related learning and
      memory deficits. We examined the effects of EVOO on learning and memory in SAMP8
      mice, an age-related learning/memory impairment model associated with increased
      amyloid-beta protein and brain oxidative damage. We administered EVOO, coconut
      oil, or butter to 11 month old SAMP8 mice for 6 weeks. Mice were tested in T-maze
      foot shock avoidance and one-trial novel object recognition with a 24 h delay.
      Mice which received EVOO had improved acquisition in the T-maze and spent more
      time with the novel object in one-trial novel object recognition versus mice
      which received coconut oil or butter. Mice that received EVOO had improve T-maze
      retention compared to the mice that received butter. EVOO increased brain
      glutathione levels suggesting reduced oxidative stress as a possible mechanism.
      These effects plus increased glutathione reductase activity, superoxide dismutase
      activity, and decreased tissue levels of 4-hydroxynoneal and 3-nitrotyrosine were
      enhanced with enriched EVOO (3 * and 5 * polyphenols concentration). Our findings
      suggest that EVOO has beneficial effects on learning and memory deficits found in
      aging and diseases, such as those related to the overproduction of amyloid-beta
      protein, by reversing oxidative damage in the brain, effects that are augmented
      with increasing concentrations of polyphenols in EVOO.

PMID- 21955813
TI  - (1)H-MRS evaluation of therapeutic effect of neural stem cell transplantation on
      Alzheimer's disease in AbetaPP/PS1 double transgenic mice.
AB  - The aim of this work was to explore the applicable value of (1)H-MRS evaluation
      on the treatment of Alzheimer's disease (AD) with neural stem cell (NSC)
      transplantation by quantitative analysis of metabolite changes in the hippocampal
      area in AbetaPP/PS1 transgenic (tg) mice. The tg mice (n = 30) aged 12 months
      were randomized into two subgroups: One receiving NSCs and the other receiving
      PBS transplantation in the bilateral hippocampal CA1 region. The wild-type mice
      (n = 15) were used as the control group. (1)H-MRS was performed before
      transplantation and 6 weeks after transplantation to measure the change of N
      acetylaspartate (NAA), myo-inositol (mI), glutamate (Glu), choline (Cho), and
      creatine (Cr) in the hippocampus. Results showed NAA and Glu levels were
      increased and mI level was decreased in NSC group compared with the PBS group at
      six weeks after transplantation (p < 0.05). There was no significant difference
      in NAA and Glu (p > 0.05), and there was significant difference in mI (p < 0.05)
      between NSC and control groups. However, there was no significant difference in
      Cho before and after transplantation among the three groups (p > 0.05). Histology
      showed the number of neurons in the hippocampal CA1 region increased
      significantly in the NSC group than those in the PBS group (p < 0.05), and the
      number of astrocytes significantly decreased in the NSC group compared with the
      PBS group. Ultrastructure showed that the neurons in the NSC group were
      morphologically normal. In conclusion, (1)H-MRS can display intracranial
      metabolite changes before and after NSC transplantation in tg mice and has a
      applicable value in evaluating the therapeutic effect of NSCs on AD.

PMID- 21955814
TI  - Neuroinflammation, hyperphosphorylated tau, diffuse amyloid plaques, and down
      regulation of the cellular prion protein in air pollution exposed children and
      young adults.
AB  - Air pollution exposures have been linked to neuroinflammation and neuropathology.
      Autopsy samples of the frontal cortex from control (n = 8) and pollution-exposed
      (n = 35) children and young adults were analyzed by RT-PCR (n = 43) and
      microarray analysis (n = 12) for gene expression changes in oxidative stress, DNA
      damage signaling, NFkappaB signaling, inflammation, and neurodegeneration
      pathways. The effect of apolipoprotein E (APOE) genotype on the presence of
      protein aggregates associated with Alzheimer's disease (AD) pathology was also
      explored. Exposed urbanites displayed differential (>2-fold) regulation of 134
      genes. Forty percent exhibited tau hyperphosphorylation with pre-tangle material
      and 51% had amyloid-beta (Abeta) diffuse plaques compared with 0% in controls.
      APOE4 carriers had greater hyperphosphorylated tau and diffuse Abeta plaques
      versus E3 carriers (Q = 7.82, p = 0.005). Upregulated gene network clusters
      included IL1, NFkappaB, TNF, IFN, and TLRs. A 15-fold frontal down-regulation of
      the prion-related protein (PrP(C)) was seen in highly exposed subjects. The down
      regulation of the PrP(C) is critical given its important roles for
      neuroprotection, neurodegeneration, and mood disorder states. Elevation of
      indices of neuroinflammation and oxidative stress, down-regulation of the PrP(C)
      and AD-associated pathology are present in young megacity residents. The
      inducible regulation of gene expression suggests they are evolving different
      mechanisms in an attempt to cope with the constant state of inflammation and
      oxidative stress related to their environmental exposures. Together, these data
      support a role for air pollution in CNS damage and its impact upon the developing
      brain and the potential etiology of AD and mood disorders.

PMID- 21955815
TI  - Memantine and functional communication in Alzheimer's disease: results of a 12
      week, international, randomized clinical trial.
AB  - Post hoc analyses suggest that memantine treatment may provide communication
      related benefits in patients with Alzheimer's disease (AD). In this 12-week,
      international, randomized, double-blind, placebo-controlled trial of memantine
      (10 mg bid), the functional communication abilities of patients with AD (MMSE
      range: 10-19) were assessed using the Functional Linguistic Communication
      Inventory (FLCI; primary measure). Two combined subscales (Social Communication
      and Communication of Basic Needs) from the American Speech-Language-Hearing
      Association Functional Assessment of Communication Skills for Adults (ASHA FACS;
      secondary measure) were administered to caregivers. Treatment-emergent adverse
      events were also recorded. After 12 weeks, memantine-treated patients (n = 133)
      demonstrated a non-significant improvement on the FLCI (placebo: -0.6; memantine:
      0.7; p = 0.070, LOCF) and a significant improvement on the ASHA FACS (placebo: 
      5.3; memantine: 0.5; p = 0.022), compared with placebo-treated patients (n =
      124). Memantine had a low incidence of adverse events. In patients with moderate
      AD, memantine treatment improved functional communication, as recognized by
      caregivers.

PMID- 21955816
TI  - Evaluation of plasma Abeta as predictor of Alzheimer's disease in older
      individuals without dementia: a population-based study.
AB  - Amyloid-beta (Abeta) pathology is a major component in the mechanisms behind
      Alzheimer's disease (AD). Measurement of Abeta(42) in cerebrospinal fluid
      predicts cognitive decline in patients with mild cognitive impairment and
      identifies AD in patients with dementia. However, studies on Abeta in plasma are
      contradictory. In this prospective population-based study, plasma Abeta(42) and
      Abeta(40) were measured at baseline in 730 adults aged 70 years or older and
      without dementia. After five years, plasma levels were analyzed again and
      participants were assessed for development of dementia. During follow-up, 53
      individuals (7%) developed dementia of which 37 (5%) were classified as AD. No
      difference in baseline plasma Abeta(42), Abeta(40), or Abeta(42)/Abeta(40) ratio
      levels were observed between converters to dementia or AD compared to the
      cognitively stable individuals. However, individuals with plasma Abeta(40) levels
      above the median level for the group at baseline had an increased risk of
      developing dementia and AD during the follow-up, even after adjustment for age,
      gender, APOE genotype, and educational level (odds ratio = 2.2, 95% confidence
      interval = 1.0-4.7, p < 0.05). Neither plasma Abeta(42) nor the
      Abeta(42)/Abeta(40) ratio influenced the risk of developing dementia or AD.
      Moreover, Abeta(42) and Abeta(40) levels increased over the 5 years, whereas the
      Abeta(42)/Abeta(40) ratio decreased (p < 0.001). In conclusion, this study
      suggests that measurement of plasma Abeta should not be used clinically to
      predict dementia or AD. However, plasma Abeta(40) may possibly be regarded as a
      moderate risk marker comparable to other risk markers for AD such as first-degree
      family history of dementia.

PMID- 21955817
TI  - Lipid mediators and their metabolism in the nucleous: implications for
      Alzheimer's disease.
AB  - Lipid mediators are important endogenous regulators derived from enzymatic
      degradation of glycerophospholipids, sphingolipids, and cholesterol by
      phospholipases, sphingomyelinases, and cytochrome P450 hydroxylases,
      respectively. In neural cells, lipid mediators are associated with proliferation,
      differentiation, oxidative stress, inflammation, and apoptosis. A major group of
      lipid mediators, which originates from the enzymatic oxidation of arachidonic
      acid, is called eicosanoids (i.e., prostaglandins, leukotrienes, thromboxanes,
      and lipoxins). The corresponding lipid mediators of docosahexaenoic acid
      metabolism are named as docosanoids. They include resolvins, protectins
      (neuroprotectins), and maresins. Docosanoids produce antioxidant, anti
      inflammatory, and antiapoptotic effects in brain tissue. Other
      glycerophospholipid-derived lipid mediators are platelet activating factor,
      lysophosphatidic acid, and endocannabinoids. Degradation of sphingolipids also
      results in the generation of sphingolipid-derived lipid mediators, such as
      ceramide, ceramide 1-phosphate, sphingosine, and sphingosine 1-phosphate. These
      mediators are involved in differentiation, growth, cell migration, and apoptosis.
      Similarly, cholesterol-derived lipid mediators, hydroxycholesterol, produce
      apoptosis. Abnormal metabolism of lipid mediators may be closely associated with
      pathogenesis of Alzheimer's disease.

PMID- 21955818
TI  - Gantenerumab: a novel human anti-Abeta antibody demonstrates sustained cerebral
      amyloid-beta binding and elicits cell-mediated removal of human amyloid-beta.
AB  - The amyloid-beta lowering capacity of anti-Abeta antibodies has been demonstrated
      in transgenic models of Alzheimer's disease (AD) and in AD patients. While the
      mechanism of immunotherapeutic amyloid-beta removal is controversial, antibody
      mediated sequestration of peripheral Abeta versus microglial phagocytic activity
      and disassembly of cerebral amyloid (or a combination thereof) has been proposed.
      For successful Abeta immunotherapy, we hypothesized that high affinity antibody
      binding to amyloid-beta plaques and recruitment of brain effector cells is
      required for most efficient amyloid clearance. Here we report the generation of a
      novel fully human anti-Abeta antibody, gantenerumab, optimized in vitro for
      binding with sub-nanomolar affinity to a conformational epitope expressed on
      amyloid-beta fibrils using HuCAL((r)) phage display technologies. In peptide
      maps, both N-terminal and central portions of Abeta were recognized by
      gantenerumab. Remarkably, a novel orientation of N-terminal Abeta bound to the
      complementarity determining regions was identified by x-ray analysis of a
      gantenerumab Fab-Abeta(1-11) complex. In functional assays gantenerumab induced
      cellular phagocytosis of human amyloid-beta deposits in AD brain slices when co
      cultured with primary human macrophages and neutralized oligomeric Abeta42
      mediated inhibitory effects on long-term potentiation in rat brain. In
      APP751(swedish)xPS2(N141I) transgenic mice, gantenerumab showed sustained binding
      to cerebral amyloid-beta and, upon chronic treatment, significantly reduced small
      amyloid-beta plaques by recruiting microglia and prevented new plaque formation.
      Unlike other Abeta antibodies, gantenerumab did not alter plasma Abeta suggesting
      undisturbed systemic clearance of soluble Abeta. These studies demonstrated that
      gantenerumab preferentially interacts with aggregated Abeta in the brain and
      lowers amyloid-beta by eliciting effector cell-mediated clearance.

PMID- 21955819
TI  - Solitary skin metastasis from sarcomatoid carcinoma of the bladder: a case
      report.
AB  - INTRODUCTION: Cutaneous metastases from carcinomas of the bladder are very rare.
      They are related to advanced stages of the disease and have poor prognosis with
      low survival rates. The common treatment modality of cutaneous metastases from a
      primary bladder cancer is wide local excision followed by chemotherapy. CASE
      PRESENTATION: We report a case of solitary skin metastasis from a rare type of
      urinary bladder carcinoma in a 68 year-old Caucasian man. Urinary bladder
      carcinoma metastasizing to the skin is an uncommon finding despite the high
      incidence of this tumor. Skin metastasis generally presents in the late stages of
      this disease and indicates a poor outcome. CONCLUSIONS: Because of the extremely
      aggressive malignant potential of sarcomatoid carcinomas, the indications for a
      transurethral resection of the bladder should be carefully assessed and suitable
      therapeutic strategies should be examined further.

PMID- 21955821
TI  - Social marketing and the creative process: staying true to your social marketing
      objectives.
AB  - Developing the promotional strategy is often the most exciting and enjoyable part
      of the social marketing plan. Health communication and social marketing campaigns
      that combine mass media with the distribution of health-related products, such as
      child safety restraints and sun protection products, have shown strong evidence
      of effectiveness for producing intended behavior changes (Guide to Community
      Preventive Services, 2010). This article discusses the promotional aspect of
      social marketing plans--the fourth P in the marketing mix that includes product,
      place, and price--and how public health practitioners can work with creative
      professionals to be sure that the creative development and execution of
      promotional messages and materials stay "on strategy" and support their
      objectives.

PMID- 21955822
TI  - Using Photovoice to assess and promote environmental approaches to tobacco
      control in AAPI communities.
AB  - Asian American and Pacific Islander (AAPI) communities face enormous health
      disparities, with tobacco use contributing to high rates of cancer and heart
      disease. There is growing interest nationwide on the influence of environmental
      factors on tobacco use. AAPI communities have been found to have higher exposures
      to tobacco company marketing compared to the general population. The authors
      describe the use of Photovoice (a qualitative needs assessment technique) to
      empower AAPI youth to identify and understand environmental characteristics
      associated with tobacco use in four AAPI communities in California and
      Washington. Of the six major environmental themes identified from the photos,
      three themes were found across all four communities. Debrief sessions with youth
      and community leaders underscore the relevance of Photovoice for identifying
      community needs and motivating community organization for change. Despite some
      logistical challenges, Photovoice exemplifies the power and potential of this
      community-based methodology to capture how the environment influences youth on
      tobacco use.

PMID- 21955823
TI  - Quantitative monitoring of BCR/ABL1 mutants for surveillance of subclone
      evolution, -expansion, and -depletion in chronic myeloid leukaemia.
AB  - BACKGROUND: In chronic myeloid leukaemia (CML), clonal evolution with resistance
      to tyrosine kinase inhibitors (TKIs) is often triggered by BCR/ABL1 mutations.
      However, in the context of the complex pro-oncogenic signalling networks which
      ultimately lead to clonal expansion and disease progression, the exact
      contribution of BCR/ABL1 mutants remains uncertain. Recent data indicate that
      detection of BCR/ABL1 mutant subclones does not permit prediction of their
      expansion dynamics and their potential to become drivers of resistant disease.
      METHODS: To determine the patterns of clonal evolution and the distinct
      proliferation kinetics of individual BCR/ABL1 mutants during treatment, we
      employed ligase-dependent polymerase chain reaction (LD-PCR) analysis for
      quantitative surveillance of CML subclones with various tyrosine kinase domain
      (TKD) mutations including M244V, L248V, G250E, E255K, T315I, F317L-A/G, M351T and
      F359V. FINDINGS: Inadequate treatment responses were observed in 27 of 100
      patients investigated and 16 were found to bear one or more BCR/ABL1 TKD
      mutations in separate subclones. Rapid subclone expansion upon onset or switch of
      TKI treatment was common and sometimes preceded corresponding changes in BCR/ABL1
      transcript levels. Mutant subclones were found to respond differentially and
      sometimes unexpectedly to various treatment modalities. Decline and persistent
      depletion of specific mutation-bearing subclones in response to treatment could
      be documented by LD-PCR surveillance. INTERPRETATION: The observations show that
      quantitative monitoring of mutant BCR/ABL1 subclones by LD-PCR is a powerful tool
      for detection of clonal evolution, subclone-expansion and subclone-depletion and
      can contribute to optimised management of patients with CML.

PMID- 21955825
TI  - Poststernotomy pain: a clinical review.

PMID- 21955824
TI  - Loss of the Drosophila cell polarity regulator Scribbled promotes epithelial
      tissue overgrowth and cooperation with oncogenic Ras-Raf through impaired Hippo
      pathway signaling.
AB  - BACKGROUND: Epithelial neoplasias are associated with alterations in cell
      polarity and excessive cell proliferation, yet how these neoplastic properties
      are related to one another is still poorly understood. The study of Drosophila
      genes that function as neoplastic tumor suppressors by regulating both of these
      properties has significant potential to clarify this relationship. RESULTS: Here
      we show in Drosophila that loss of Scribbled (Scrib), a cell polarity regulator
      and neoplastic tumor suppressor, results in impaired Hippo pathway signaling in
      the epithelial tissues of both the eye and wing imaginal disc. scrib mutant
      tissue overgrowth, but not the loss of cell polarity, is dependent upon defective
      Hippo signaling and can be rescued by knockdown of either the TEAD/TEF family
      transcription factor Scalloped or the transcriptional coactivator Yorkie in the
      eye disc, or reducing levels of Yorkie in the wing disc. Furthermore, loss of
      Scrib sensitizes tissue to transformation by oncogenic Ras-Raf signaling, and
      Yorkie-Scalloped activity is required to promote this cooperative tumor
      overgrowth. The inhibition of Hippo signaling in scrib mutant eye disc clones is
      not dependent upon JNK activity, but can be significantly rescued by reducing
      aPKC kinase activity, and ectopic aPKC activity is sufficient to impair Hippo
      signaling in the eye disc, even when JNK signaling is blocked. In contrast, warts
      mutant overgrowth does not require aPKC activity. Moreover, reducing endogenous
      levels of aPKC or increasing Scrib or Lethal giant larvae levels does not promote
      increased Hippo signaling, suggesting that aPKC activity is not normally rate
      limiting for Hippo pathway activity. Epistasis experiments suggest that Hippo
      pathway inhibition in scrib mutants occurs, at least in part, downstream or in
      parallel to both the Expanded and Fat arms of Hippo pathway regulation.
      CONCLUSIONS: Loss of Scrib promotes Yorkie/Scalloped-dependent epithelial tissue
      overgrowth, and this is also important for driving cooperative tumor overgrowth
      with oncogenic Ras-Raf signaling. Whether this is also the case in human cancers
      now warrants investigation since the cell polarity function of Scrib and its
      capacity to restrain oncogene-mediated transformation, as well as the tissue
      growth control function of the Hippo pathway, are conserved in mammals.

PMID- 21955826
TI  - Cardioprotection by volatile anesthetics: what about noncardiac surgery?

PMID- 21955827
TI  - A word of caution regarding transesophageal echocardiography and penetrating
      chest trauma.

PMID- 21955828
TI  - Echocardiographic evaluation of systolic and diastolic function: a preoperative
      study of correlation with serum NT-proBNP.
AB  - OBJECTIVE: The authors hypothesized that preoperative N-terminal probrain
      natriuretic peptide (NT-proBNP) correlates well with longitudinal strain
      measurements and with Doppler measurements of diastolic function. DESIGN:
      Prospective observational study. SETTING: University teaching hospital.
      PARTICIPANTS: Forty patients undergoing elective cardiac surgery. INTERVENTIONS:
      Aortic valve replacement, coronary artery bypass grafting, or a combination of
      these procedures. MEASUREMENTS AND MAIN RESULTS: Plasma NT-proBNP concentration
      was obtained by analyzing blood samples with a commercially available kit. Left
      ventricular systolic function was assessed by speckle tracking ultrasound strain
      measurements and left ventricular diastolic function was assessed by 2 Doppler
      methods: E/A ratio and E/E' ratio. Tissue Doppler imaging velocities (E' and A')
      were measured in the basal septum (annular) and pulse-wave Doppler was used to
      measure mitral in-flow profile (E and A). The correlation between global strain
      data from the speckle tracking ultrasound measurement and NT-proBNP levels was
      rho = 0.35 (p = 0.026). With a cutoff value of -15% in global strain
      measurements, there was a significant difference in NT-proBNP levels (117 v 57
      pg/mL, p = 0.048). E/E' values correlated with NT-proBNP levels (rho = 0.46, p =
      0.011). With a cutoff of 15 in E/E' values, there were significant differences in
      corresponding NT-proBNP levels (33 v 113 pg/mL, p = 0.004). CONCLUSIONS: A
      correlation was found between plasma levels of NT-proBNP and speckle tracking
      ultrasound strain measurements by an easily employed method applicable in the
      anesthesia and preoperative settings. In addition, the well-established marker of
      diastolic function, E/E', correlated well with NT-proBNP, whereas the E/A ratio
      failed to show any association.

PMID- 21955829
TI  - Fibrinogen concentrate therapy guided by thromboelastometry as an alternative to
      fresh frozen plasma in major vascular surgery.

PMID- 21955830
TI  - Comparison of the analgesic effects of continuous extrapleural block and
      continuous epidural block after video-assisted thoracoscopic surgery.
AB  - DESIGN: A prospective, randomized, open study. The regional technique used was
      not blinded. SETTING: A university teaching hospital. PARTICIPANTS: Forty-eight
      patients undergoing video-assisted thoracoscopic surgery (VATS) for tumor
      resection. INTERVENTIONS: Patients received either continuous extrapleural block
      or continuous epidural block using ropivacaine for a period of 60 hours after
      surgery. MEASUREMENTS AND MAIN RESULTS: To evaluate postoperative pain control,
      the primary and secondary endpoints were the visual analog scale (VAS) on
      movement and the amount of rescue analgesia, respectively. There were no
      significant differences between the extrapleural and epidural block groups with
      regard to VAS at rest and during movement assessed at 4, 12, 24, 36, and 48 hours
      after surgery, dosage of intravenous morphine (extrapleural: 12.9 +/- 11.3,
      epidural: 10.2 +/- 6.9 mg), supplemental nonsteroidal anti-inflammatory drugs,
      incidence of postoperative nausea and vomiting (extrapleural: 12/20, epidural:
      11/20), postoperative ambulation (extrapleural: 18 at postoperative day [POD] 1
      and 20 at POD 2, epidural: 19 at POD 1 and 20 at POD 2) and hospital stay after
      surgery (extrapleural: 12.7 +/- 6.3, epidural: 12.6 +/- 4.7 days). CONCLUSIONS:
      Although this study did not show the superiority of continuous extrapleural block
      relative to continuous epidural in VATS patients, the results suggest that both
      methods provided effective analgesia with a relatively small dose of rescue
      morphine. Although the analgesic effects of these techniques were comparable,
      extrapleural block has the advantage of safety and precise placement of the
      catheter and can be considered an alternative to epidural block in VATS patients.

PMID- 21955831
TI  - Case 7-2011: Perioperative challenges of valvular replacement in patients after
      mediastinal radiation therapy.

PMID- 21955832
TI  - Coronary artery disease, acute myocardial infarction, and a newly developing
      ventricular septal defect: surgical repair or percutaneous closure?

PMID- 21955833
TI  - Epigenetics and chemoresistance in colorectal cancer: an opportunity for
      treatment tailoring and novel therapeutic strategies.
AB  - Colorectal cancer is the second leading cause of cancer-related deaths in the
      world. Despite many therapeutic opportunities, prognosis remains dismal for
      patients with metastatic disease, and a significant portion of early-stage
      patients develop recurrence after chemotherapy. Epigenetic gene regulation is a
      major mechanism of cancer initiation and progression, through the inactivation of
      several tumor suppressor genes. Emerging evidence indicates that epigenetics may
      also play a key role in the development of chemoresistance. In the present
      review, we summarize epigenetic mechanisms triggering resistance to three
      commonly used agents in colorectal cancer: 5-fluorouracil, irinotecan and
      oxaliplatin. Those epigenetic biomarkers may help stratify colorectal cancer
      patients and develop a tailored therapeutic approach. In addition, epigenetic
      modifications are reversible through specific drugs: histone-deacetylase and DNA
      methyl-transferase inhibitors. Preclinical studies suggest that these drugs may
      reverse chemoresistance in colorectal tumors. In conclusion, an epigenetic
      approach to colorectal cancer chemoresistance may pave the way to personalized
      treatment and to innovative therapeutic strategies.

PMID- 21955834
TI  - Inter-individual differences in trait negative affect moderate cortisol's effects
      on memory formation: preliminary findings from two studies.
AB  - Acute emotional arousal moderates the effects of cortisol on memory. However, it
      is currently unknown how stable inter-individual differences (i.e., traits)
      moderate cortisol's effects on memory. In two studies using within-subjects
      designs - 31 healthy males in Study 1 and 42 healthy subjects (22 female) in
      Study 2 - we measured trait negative affect (NA) and presented emotional and
      neutral pictures. In Study 1, we manipulated endogenous cortisol levels using a
      speech stressor following encoding. In Study 2, using a randomized placebo
      controlled design, we pharmacologically manipulated cortisol levels prior to
      encoding (0.1mg/kg hydrocortisone vs. saline infused over 30min). Free recall for
      pictures was subsequently assessed. Trait NA repeatedly moderated the
      relationship between cortisol and memory formation. Findings suggested the
      speculative conclusion that the direction of effects may vary by sex. In males,
      cortisol was related to memory facilitation in subjects with lower Trait NA.
      Conversely, females with higher Trait NA showed greater cortisol-related
      increases in memory. Trait NA may be a stable inter-individual difference
      predicting neurocognitive effects of cortisol during stressors.

PMID- 21955835
TI  - Preservation of protein globules and peptidoglycan in the mineralized cell wall
      of nitrate-reducing, iron(II)-oxidizing bacteria: a cryo-electron microscopy
      study.
AB  - Iron-oxidizing bacteria are important actors of the geochemical cycle of iron in
      modern environments and may have played a key role all over Earth's history.
      However, in order to better assess that role on the modern and the past Earth,
      there is a need for better understanding the mechanisms of bacterial iron
      oxidation and for defining potential biosignatures to be looked for in the
      geologic record. In this study, we investigated experimentally and at the
      nanometre scale the mineralization of iron-oxidizing bacteria with a combination
      of synchrotron-based scanning transmission X-ray microscopy (STXM), scanning
      transmission electron microscopy (STEM) and cryo-transmission electron microscopy
      (cryo-TEM). We show that the use of cryo-TEM instead of conventional microscopy
      provides detailed information of the successive iron biomineralization stages in
      anaerobic nitrate-reducing iron-oxidizing bacteria. These results suggest the
      existence of preferential Fe-binding and Fe-oxidizing sites on the outer face of
      the plasma membrane leading to the nucleation and growth of Fe minerals within
      the periplasm of these cells that eventually become completely encrusted. In
      contrast, the septa of dividing cells remain nonmineralized. In addition, the use
      of cryo-TEM offers a detailed view of the exceptional preservation of protein
      globules and the peptidoglycan within the Fe-mineralized cell walls of these
      bacteria. These organic molecules and ultrastructural details might be protected
      from further degradation by entrapment in the mineral matrix down to the
      nanometre scale. This is discussed in the light of previous studies on the
      properties of Fe-organic interactions and more generally on the fossilization of
      mineral-organic assemblies.

PMID- 21955836
TI  - [Teaching surgery: new times, new methods].
AB  - INTRODUCTION: The organisation, follow-up and quality of post-graduate teaching
      may be in need of appraisal in our area. This study sets out a clear objective:
      to use a more practical and effective teaching tool than we currently have
      available. Not only will it set out to assess the resident, but also provide
      material already approved and reviewed by their tutors. All this will be achieved
      using an easy, accessible and free method which ensures their basic training.
      MATERIAL AND METHOD: Firstly, we identified the practical problems in the general
      surgery residency in our area. We prepared a questionnaire and sent it by e-mail
      to all second year and over residents of the Basque Country Autonomous Community.
      From the results obtained, we designed a file system with Google DocumentsTM and
      we started to apply it the third and fourth years. RESULTS: The teaching methods
      in Surgery have partly become obsolete due to the initiative of Information
      Sciences Technology. The new generations naturally dominate the Internet along
      with the more common computer applications. Within our reach we have a series of
      tools that, due to lack of knowledge or lack of time, we do not use. This article
      attempts to provide a working option that will help the job of the tutor as a
      teaching figure, since the health care activity often has no place for
      interaction with the resident.

PMID- 21955837
TI  - [Recommendations for the peri-operative management of bariatric surgery patients:
      results of a national survey].
AB  - To standardise possible peri-operative bariatric surgery protocols, a survey was
      prepared to be filled in by members of the Spanish Society for Obesity (Sociedad
      Espanola de Cirugia de la Obesidad) (SECO), and to approve it at the XII National
      Congress. A total of 47 members of SECO from 14 autonomous communities responded,
      and it unanimously approved by the Congress. As highly recommended peri-operative
      procedures, were proposed: full laboratory analysis (98%) with an endocrine study
      (90%), ECG (96%), chest x-ray (98%), an oesophageal-gastric imaging test
      (endoscopy or gastro-duodenal transit study (98%), antibiotic prophylaxis (92%)
      and use of low molecular weight heparins pre-operatively (96%), and for 2 weeks
      (83%). Pre-surgical, abdominal ultrasound (86%), spirometry (80%), diet (88%) and
      psychological study (76%), and during surgery, use of elastic stockings (76%),
      leak tests (92%) and drainages (90%), were established as advisable procedures.

PMID- 21955838
TI  - [Two years experience of computerised medical records in a regional hospital].
AB  - The introduction of computerised medical records in public hospitals is, without
      a doubt, one of the biggest changes made in patient health care in the last few
      years. It is a gradual process and is not exempt from difficulties, but it will
      surely set a challenge in the way information is handled in health care. Taking
      this path, in November 2008, the computer program SELENE, from the multinational
      company Siemens, was purchased in the centre were we carry out our surgical
      activities. The introduction of this program was preceded by an intensive
      training course for all the workers in the hospital. At the start, it was decided
      that the computer application would come into operation throughout the entire
      hospital, replacing the handwritten records. There were difficult days during its
      gradual introduction, but the computerised medical record has been well accepted
      by the great majority of the workers at the centre. After the initial stage of
      becoming accustomed, design problems started to be seen in the application, as
      well as their possible solutions. Currently, the use of the SELENE program has
      led to fluid health care within the hospital, although there are problems which
      can be resolved with adequate funding.

PMID- 21955839
TI  - Weak association of anti-sperm antibodies and strong association of familial
      cryptorchidism/infertility with HLA-DRB1 polymorphisms in prepubertal Ukrainian
      boys.
AB  - BACKGROUND: Cryptorchidism is a frequent syndrome occurring in 1-2% of males
      within the first year of age. Autoimmune reactions, particularly directed to
      testicular elements and/or spermatozoa have been found to be often associated
      with cryptorchidism. Therefore we investigated in this study the frequency of HLA
      class II alleles in order to recognize possible genetic predisposition for
      antisperm antibodies development in prepubertal boys with diagnosed
      cryptorchidism in Caucasoid population. METHODS: Sixty prepubertal boys with
      cryptorchidism and sixty healthy boys were examined for anti-sperm antibodies by
      indirect immunobead test as well as for their HLA-DRB1 and -DQB1 alleles using
      DNA obtained from peripheral blood leukocytes. The typing of HLA-DRB1 and -DQB1
      was performed by using PCR-SSP low resolution method. RESULTS: Allele frequencies
      of HLA-DRB1 and HLA-DQB1 did not differ between boys with cryptorchidism and
      control boys. However, weakly significant differences in DRB1*04 (p
      corrected=0.0475) and DQB1*06 (p corrected=0.0385) were seen between cryptorchid
      patients with and without AsA, but none of these two patient groups differed
      significantly in HLA class II frequencies from controls except for AsA-negatives
      and HLA-DQB1*06 (p corrected=0.0247). On the other hand, comparison of
      cryptorchid boys with familial cryptorchidism and/or infertility to control boys
      revealed highly significant (p corrected=0.0006) difference in HLA-DRB*11
      frequency, whereas boys with sporadic cryptorchidism did not differ from control.
      A much weaker, but still significant difference in DRB*11 frequency was also
      observed between boys with bilateral cryptorchidism and controls (p
      corrected=0.037), whereas patients with unilateral cryptorchidism were not
      different from control in frequency of any HLA-DRB1 or -DQB1 allele tested.
      CONCLUSIONS: Predisposition to produce anti-sperm antibodies seems to be only
      weakly associated with HLA class II genes, although this question requires
      further study on much larger population sample. It is plausible that familial and
      sporadic cryptorchidism may present distinct genetic background. The same may, to
      lower extent, apply to bilateral and unilateral cryptorchidism.

PMID- 21955840
TI  - Identifying and overcoming the constraints that prevent the full implementation
      of decommissioning and remediation programs in uranium mining sites.
AB  - Environmental remediation of radioactive contamination is about achieving
      appropriate reduction of exposures to ionizing radiation. This goal can be
      achieved by means of isolation or removal of the contamination source(s) or by
      breaking the exposure pathways. Ideally, environmental remediation is part of the
      planning phase of any industrial operation with the potential to cause
      environmental contamination. This concept is even more important in mining
      operations due to the significant impacts produced. This approach has not been
      considered in several operations developed in the past. Therefore many legacy
      sites face the challenge to implement appropriate remediation plans. One of the
      first barriers to remediation works is the lack of financial resources as
      environmental issues used to be taken in the past as marginal costs and were not
      included in the overall budget of the company. This paper analyses the situation
      of the former uranium production site of Pocos de Caldas in Brazil. It is
      demonstrated that in addition to the lack of resources, other barriers such as
      the lack of information on site characteristics, appropriate regulatory
      framework, funding mechanisms, stakeholder involvement, policy and strategy,
      technical experience and mechanism for the appropriation of adequate technical
      expertise will play key roles in preventing the implementation of remediation
      programs. All these barriers are discussed and some solutions are suggested. It
      is expected that lessons learned from the Pocos de Caldas legacy site may
      stimulate advancement of more sustainable options in the development of future
      uranium production centers.

PMID- 21955841
TI  - Silver(I)-mediated Hoogsteen-type base pairs.
AB  - Metal-mediated Hoogsteen-type base pairs are useful for the construction of DNA
      duplexes containing contiguous stretches of metal ions along the helical axis. To
      fine-tune the stability of such base pairs and the selectivity toward different
      metal ions, the availability of a selection of artificial nucleobases is highly
      desirable. In this study, we follow a theoretical approach utilizing dispersion
      corrected density functional methods to evaluate a variety of artificial
      nucleobases as candidates for metal-mediated Hoogsteen-type base pairs. We focus
      on silver(I)-mediated Hoogsteen- and reverse Hoogsteen-type base pairs formed
      between 1-deaza- and 1,3-dideazapurine-derived nucleobases, respectively, and
      cytosine. Apart from two coordinative bonds, these base pairs are stabilized by a
      hydrogen bond. We elucidate the impact of different substituents at the C6
      position and the presence or absence of an endocyclic N3 nitrogen atom on the
      overall stability of a base pair and concomitantly on the strength of the
      hydrogen and coordinative bonds. All artificial base pairs investigated in this
      study are less stable than the experimentally established benchmark base pair C
      Ag(+)-G. The base pair formed from 1,3-dideaza-6-methoxypurine is isoenergetic to
      the experimentally observed C-Ag(+)-C base pair. This makes 1,3-dideaza-6
      methoxypurine a promising candidate for the use as an artificial nucleobase in
      DNA.

PMID- 21955842
TI  - Reduction of the lipocalin type heme containing protein nitrophorin --
      sensitivity of the fold-stabilizing cysteine disulfides toward routine heme-iron
      reduction.
AB  - The determination of the redox properties of the cofactor in heme proteins
      provides fundamental insight into the chemical characteristics of this wide
      spread class of metalloproteins. For the preparation of the ferroheme state,
      probably the most widely applied reductant is sodium dithionite, which at neutral
      pH has a reduction potential well below the reduction potential of most heme
      centers. In addition to the heme iron, some heme proteins, including the
      nitrophorins (NPs), contain cysteinecysteine disulfide bonds. In the present
      study, the effect of dithionite on the disulfides of NP4 and NP7 is addressed. To
      gain deeper understanding of the disulfide/dithionite reaction, oxidized
      glutathione (GSSG), as a model system, was incubated with dithionite and the
      products were characterized by (13)C NMR spectroscopy and reverse phase
      chromatography in combination with mass spectrometry. This revealed the formation
      of one equivalent each of thiol (GSH) and glutathione-S-thiosulfate (GSSO(3)(-)).
      With this background information, the effect of dithionite on the cystines of NP4
      and NP7 was studied after trapping of the thiols with para-cloromercurybenzyl
      sulfonate (p-CMBS) and subsequent matrix assisted laser desorption/ionization
      time-of-flight mass spectrometry (MALDI-TOF MS) where the heterolytic cleavage of
      the SS bond appears with only 2molar equivalents of the reductant. Furthermore,
      prolonged electrochemical reduction of NP4 and NP7 in the presence of
      electrochemical mediators also leads to disulfide breakage. However, due to
      sterical shielding of the disulfide bridges in NP4 and NP7, the cystine reduction
      can be largely prevented by the use of stoichiometric amounts of reductant or
      limited electrochemical reduction. The described disulfide breakage during
      routine iron reduction is of importance for other heme proteins containing
      cystine(s).

PMID- 21955843
TI  - Synthesis, characterization and antitumor activity of polymeric copper(II)
      complexes with thiosemicarbazones of 3-methyl-5-oxo-1-phenyl-3-pyrazolin-4
      carboxaldehyde and 5-oxo-3-phenyl-3-pyrazolin-4-carboxaldehyde.
AB  - New polymeric copper(II) complexes with two tridentate ONS thiosemicarbazone
      ligands containing substituted pyrazolone moiety were synthesized and
      characterized by means of spectroscopic, electrochemical and crystallographic
      techniques. While both ligands exist as different tautomers in the solid state
      and DMSO-d(6) solution, Cu(II) ion coordinates the ligands from the same
      tautomeric form with square-pyramidal geometry around each Cu atom. In the
      crystal structures, the copper(II) complex cation forms polymeric chains
      {[Cu(L)Cl](+)}(n) with a bridging chlorine atom. One of the complexes was found
      to have a significantly higher cytotoxic potential in comparison with cisplatin
      in inhibition of several cell lines (HL60, REH, C6, L929 and B16). The results
      obtained on the basis of flow cytometry indicated that apoptosis could be
      possible mechanism of cell death.

PMID- 21955845
TI  - Physical activity and aging: a life-long story.
AB  - The benefits of physical activity in preventing premature mortality have been
      established by a large set of epidemiological studies. These benefits have been
      shown both in middle-aged and elderly individuals. Furthermore, the reduction of
      acute events such as myocardial infarction observed with higher levels of
      physical activity together with the increase in disease-free life expectancy
      among the most active individuals supports physical activity's anti-aging effect.
      This review highlights two models supporting this effect. The first model
      describes the path to frailty and the second explains that immobilization is a
      stressor which triggers stress-responses responsible for many chronic diseases.
      Aging reduces the physiological reserve and can lead to frailty when this reserve
      cannot allow an appropriate adaptation of the aging body to environmental
      challenges. The components of this physiological reserve can easily be measured
      by cardiorespiratory testing. Among them are heart rate reserve and VO(2max), the
      maximal body oxygen consumption. The opposite effects of exercise training and
      aging on the physiological reserve are detailed. Underlying mechanisms of both
      exercise training and aging are described. Sedentary lifestyle accelerates the
      effects of aging in susceptible individuals. Sedentary lifestyle induces
      mechanisms which lead to risk factors of chronic diseases and, eventually, to
      premature death. These pathological mechanisms and their consequences constitute
      the sedentary lifestyle syndrome.

PMID- 21955844
TI  - Ribonucleotide reductase inhibition by metal complexes of Triapine (3
      aminopyridine-2-carboxaldehyde thiosemicarbazone): a combined experimental and
      theoretical study.
AB  - Triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone, 3-AP) is currently
      the most promising chemotherapeutic compound among the class of alpha-N
      heterocyclic thiosemicarbazones. Here we report further insights into the
      mechanism(s) of anticancer drug activity and inhibition of mouse ribonucleotide
      reductase (RNR) by Triapine. In addition to the metal-free ligand, its iron(III),
      gallium(III), zinc(II) and copper(II) complexes were studied, aiming to correlate
      their cytotoxic activities with their effects on the diferric/tyrosyl radical
      center of the RNR enzyme in vitro. In this study we propose for the first time a
      potential specific binding pocket for Triapine on the surface of the mouse R2 RNR
      protein. In our mechanistic model, interaction with Triapine results in the
      labilization of the diferric center in the R2 protein. Subsequently the Triapine
      molecules act as iron chelators. In the absence of external reductants, and in
      presence of the mouse R2 RNR protein, catalytic amounts of the iron(III)-Triapine
      are reduced to the iron(II)-Triapine complex. In the presence of an external
      reductant (dithiothreitol), stoichiometric amounts of the potently reactive
      iron(II)-Triapine complex are formed. Formation of the iron(II)-Triapine complex,
      as the essential part of the reaction outcome, promotes further reactions with
      molecular oxygen, which give rise to reactive oxygen species (ROS) and thereby
      damage the RNR enzyme. Triapine affects the diferric center of the mouse R2
      protein and, unlike hydroxyurea, is not a potent reductant, not likely to act
      directly on the tyrosyl radical.

PMID- 21955846
TI  - Gut-mediated and HLA-B27-associated arthritis: an emphasis on ankylosing
      spondylitis and Crohn's disease with a proposal for the use of new treatment.
AB  - Ankylosing spondylitis (AS) and Crohn's disease (CD), especially when associated
      with spondylitis are interrelated conditions included within the categories of
      spondyloarthropathic disease entities. They share some common clinical, genetic,
      and microbiological findings. An extensive amount of studies which have been
      carried out by various independent groups throughout the world have shown that
      Klebsiella pneumoniae microorganisms could be suggested as the most likely
      etiopathogenetic triggers for AS and CD based on the molecular mimicry mechanism
      and the existence of the evidence for immunological, microbiological, and
      molecular link between Klebsiella and self antigens. It is proposed that the use
      of low starch diet in conjunction with the currently used treatment might help in
      the eradication of Klebsiella microbes from the bowel and could result in the
      stoppage and alleviation of the disease process in patients with AS and/or CD.

PMID- 21955847
TI  - New developments in vaccine research--unveiling the secret of vaccine adjuvants.
AB  - Since the first mass vaccination against smallpox and its eventual eradication,
      many more vaccines have been developed based on advances in bacteriology and
      virology and the use of attenuated live or killed whole pathogens. Immunological
      discoveries have allowed the development of more refined anti-toxin and conjugate
      vaccines, while biotechnology provided the tools for rationally designed,
      genetically engineered vaccines. Many challenges remain in developing safer and
      more effective vaccines against the more complex diseases such as tuberculosis
      and HIV-AIDS, and for the rapid protection against newly emerging pathogens or
      pathogen strains. These vaccines are likely to require the isolation of the
      "protective" antigenic molecules from the whole pathogen, as well as ways to
      deliver these to induce effective immune responses with minimal side effects. It
      has long been recognized that most antigens require the addition of an
      "adjuvant," an ill-defined substance that non-specifically triggers the innate
      immune system and boosts an immune response, with aluminum-based adjuvants the
      most commonly used in most present vaccines. Recent immunological breakthroughs
      have uncovered that the innate immune system has a much higher degree of
      complexity than previously thought and can be activated along a wide range of
      different pathways, depending on the engagement of different innate immune
      receptors. This in turn determines the type of immune response that will be
      generated against the vaccine antigens or pathogens. Harvesting the complexity
      and exquisite specificity of this innate immune system has inspired a new
      direction in vaccine research, towards the generation of novel adjuvant
      formulations, tailored to induce defined immune responses effective against
      specific pathogens. This review gives a brief overview of vaccine development and
      summarizes different aspects of adjuvant formulation that may influence their
      activity and specificity.

PMID- 21955848
TI  - Endometrial cancer: reviving progesterone therapy in the molecular age.
AB  - Endometrial cancer is the most common gynecologic malignancy and represents a
      major health concern because overall five-year survival rates have not improved
      in the last three decades. A great deal of research demonstrates that the
      endometrium is extremely sensitive to hormones, and a shift in the
      estrogen:progesterone balance is the major cause for the development of
      endometrial cancer. Progestin-based therapy has proven effective in a subset of
      patients, particularly in situations where expression of progesterone receptor
      (PR) is maintained. However, this approach is not routinely used in the clinic in
      the U.S. for several reasons. For example, many endometrial tumors have lost PR
      expression, which limits the clinical application of progestin-based therapy.
      While the idea that restoring PR expression will resensitize tumors to progestin
      was proposed over 20 years ago, we only now have the molecular tools to
      accomplish this goal. Basic science research has revealed several pathways that
      govern the expression of PR at the DNA, RNA, and protein levels. In this article,
      we describe one current approach to restore expression of PR at the epigenetic
      level in endometrial cancer. While still in the preclinical stage, we believe
      this strategy to re-establish PR expression will result in resensitization of
      endometrial tumors to progestin therapy.

PMID- 21955850
TI  - New insight in the mechanism of action of rituximab: the interferon signature
      towards personalized medicine.
AB  - Rheumatoid arthritis (RA) is the most common chronic inflammatory disorder of the
      musculoskeletal system that may cause permanent joint damage. The disease has a
      major impact on the quality of life of affected individuals, costs for the health
      care system, and society. Currently, no curative treatment is available, and
      patients are subjected to a prolonged course of treatment. Due to their role in
      the pathogenesis of RA, B cells have become an attractive target for therapy.
      Rituximab (Mabthera(r)/Rituxan(r)) is a therapeutic monoclonal antibody against
      CD20 expressed on B cells, which is effective in depleting B cells and approved
      worldwide for the treatment of RA. Rituximab was shown to be highly beneficial in
      decreasing clinical symptoms, safe, and well tolerated. However, clinical
      experience revealed that approximately 30-40% of RA patients do not respond to
      it. Given the destructive nature of RA, the risk of adverse effects, and
      considerable costs for therapy, there is a strong need to make predictions on the
      clinical outcome before the start of therapy. Since nearly all treated patients
      experience an effective depletion of circulating B cells, questions have been
      raised concerning the mechanism of action. In this review, novel developments, in
      particular the findings on the role of the interferon system, will be
      highlighted. This may add new and important information to our understanding of
      the mechanism that underlies the clinical outcome of rituximab treatment and may
      lead to the identification of biomarkers to predict the response.

PMID- 21955851
TI  - Arrest all accessories--inhibition of hepatitis C virus by compounds that target
      host factors.
AB  - Most novel drugs directed against the hepatitis C virus (HCV) including the
      recently approved NS3/4A protease inhibitors boceprevir and telaprevir are
      inhibitors of viral enzymes. Since HCV is an RNA virus with a short and highly
      variable genome, these direct-acting antivirals (DAAs) are prone to rapidly
      inducing the emergence of resistant HCV variants. This problem could be mitigated
      by the development of drugs that target host factors that the virus depends on
      during the various stages of its replication cycle. An increasing understanding
      of the molecular interactions between the virus and its host cell has allowed the
      identification of promising host targets for anti-HCV therapy and several host
      targeting agents (HTAs) are currently under development. The most advanced
      compounds as yet may be inhibitors of cyclophilin A, a host factor known to be
      critical for viral RNA replication and possible virion assembly or release. One
      such compound, alisporivir, has demonstrated in vivo efficacy and is now in a
      phase 3 trial. Several other HTAs with very different host targets are further
      upstream in the development pipeline. This paper reviews promising host targets,
      their role in the viral replication cycle, and the HTAs that target them.

PMID- 21955849
TI  - A mechanistically novel, first oral therapy for multiple sclerosis: the
      development of fingolimod (FTY720, Gilenya).
AB  - Multiple sclerosis (MS) is a chronic autoimmune disorder affecting the central
      nervous system (CNS) through demyelination and neurodegeneration. Until recently,
      major therapeutic treatments have relied on agents requiring injection delivery.
      In September 2010, fingolimod/FTY720 (Gilenya, Novartis) was approved by the FDA
      as the first oral treatment for relapsing forms of MS. Fingolimod is a novel
      compound produced by chemical modification of a fungal precursor. Its active
      metabolite, formed by in vivo phosphorylation, modulates sphingosine 1-phosphate
      (S1P) receptors that are a subset of a larger family of cell-surface, G protein
      coupled receptors (GPCRs) mediating the effects of bioactive lipids known as
      lysophospholipids. Fingolimod's mechanism of action in MS is not completely
      understood; however, its relevant biology indicates a fundamentally different
      mechanism compared to all previously approved MS therapies, with evolving
      research supporting both immunological and nervous system activities. This
      duality may herald a paradigm shift in the treatment of MS and other neurological
      disorders.

PMID- 21955852
TI  - Focal therapy for prostate cancer: opportunities and uncertainties.
AB  - Prostate cancer is the most common cancer and the second most common cause of
      cancer-related death in men. Screening with prostate specific antigen (PSA) has
      led to a clinical and pathological stage migration such that currently most men
      diagnosed with prostate cancer have clinically localized disease potentially
      offering opportunity for curative intervention. On the other hand, the benefit of
      radical therapy in terms of reducing overall mortality in PSA-screened
      populations has been controversial with concerns being raised about over
      diagnosis and over-treatment. Treatment of prostate cancer is associated with
      risk and complications that negatively affect the quality of life of men with
      localized disease. Recently, a new treatment paradigm has been proposed which is
      called focal therapy, defined as an individualized treatment by which only known
      disease is targeted and ablated while preserving normal tissue. This review will
      attempt to describe the opportunities and uncertainties behind this proposed
      paradigm shift.

PMID- 21955853
TI  - The potential impact of immunization campaign budget re-allocation on global
      eradication of paediatric infectious diseases.
AB  - BACKGROUND: The potential benefits of coordinating infectious disease eradication
      programs that use campaigns such as supplementary immunization activities (SIAs)
      should not be over-looked. One example of a coordinated approach is an adaptive
      "sequential strategy": first, all annual SIA budget is dedicated to the
      eradication of a single infectious disease; once that disease is eradicated, the
      annual SIA budget is re-focussed on eradicating a second disease, etc. Herd
      immunity suggests that a sequential strategy may eradicate several infectious
      diseases faster than a non-adaptive "simultaneous strategy" of dividing annual
      budget equally among eradication programs for those diseases. However,
      mathematical modeling is required to understand the potential extent of this
      effect. METHODS: Our objective was to illustrate how budget allocation strategies
      can interact with the nonlinear nature of disease transmission to determine time
      to eradication of several infectious diseases under different budget allocation
      strategies. Using a mathematical transmission model, we analyzed three
      hypothetical vaccine-preventable infectious diseases in three different
      countries. A central decision-maker can distribute funding among SIA programs for
      these three diseases according to either a sequential strategy or a simultaneous
      strategy. We explored the time to eradication under these two strategies under a
      range of scenarios. RESULTS: For a certain range of annual budgets, all three
      diseases can be eradicated relatively quickly under the sequential strategy,
      whereas eradication never occurs under the simultaneous strategy. However,
      moderate changes to total SIA budget, SIA frequency, order of eradication, or
      funding disruptions can create disproportionately large differences in the time
      and budget required for eradication under the sequential strategy. We find that
      the predicted time to eradication can be very sensitive to small differences in
      the rate of case importation between the countries. We also find that the time to
      eradication of all three diseases is not necessarily lowest when the least
      transmissible disease is targeted first. CONCLUSIONS: Relatively modest
      differences in budget allocation strategies in the near-term can result in
      surprisingly large long-term differences in time required to eradicate, as a
      result of the amplifying effects of herd immunity and the nonlinearities of
      disease transmission. More sophisticated versions of such models may be useful to
      large international donors or other organizations as a planning or portfolio
      optimization tool, where choices must be made regarding how much funding to
      dedicate to different infectious disease eradication efforts.

PMID- 21955854
TI  - Comparison of solution-based exome capture methods for next generation
      sequencing.
AB  - BACKGROUND: Techniques enabling targeted re-sequencing of the protein coding
      sequences of the human genome on next generation sequencing instruments are of
      great interest. We conducted a systematic comparison of the solution-based exome
      capture kits provided by Agilent and Roche NimbleGen. A control DNA sample was
      captured with all four capture methods and prepared for Illumina GAII sequencing.
      Sequence data from additional samples prepared with the same protocols were also
      used in the comparison. RESULTS: We developed a bioinformatics pipeline for
      quality control, short read alignment, variant identification and annotation of
      the sequence data. In our analysis, a larger percentage of the high quality reads
      from the NimbleGen captures than from the Agilent captures aligned to the capture
      target regions. High GC content of the target sequence was associated with poor
      capture success in all exome enrichment methods. Comparison of mean allele
      balances for heterozygous variants indicated a tendency to have more reference
      bases than variant bases in the heterozygous variant positions within the target
      regions in all methods. There was virtually no difference in the genotype
      concordance compared to genotypes derived from SNP arrays. A minimum of 11*
      coverage was required to make a heterozygote genotype call with 99% accuracy when
      compared to common SNPs on genome-wide association arrays. CONCLUSIONS: Libraries
      captured with NimbleGen kits aligned more accurately to the target regions. The
      updated NimbleGen kit most efficiently covered the exome with a minimum coverage
      of 20*, yet none of the kits captured all the Consensus Coding Sequence annotated
      exons.

PMID- 21955855
TI  - Impact of ABCB1 variants on neutrophil depression: a pharmacogenomic study of
      paclitaxel in 92 women with ovarian cancer.
AB  - The standard treatment for ovarian cancer in advanced stages is post-surgery
      treatment with taxane-platin chemotherapy. Despite an initial high response rate,
      most patients eventually relapse. The dose-limiting toxicities of paclitaxel are
      neutropenia and neuropathy, but the inter-individual variability is large. The
      aim of this prospective study was to investigate the impact of genetic variants
      in key drug metabolizing/transporter genes on toxicity and compliance. CYP2C8*3
      and three ABCB1 polymorphisms were chosen for primary analysis, and a host of
      other candidate genes was explored in 92 prospectively recruited Scandinavian
      Caucasian women with primary ovarian cancer who were treated with paclitaxel and
      carboplatin. A single investigator assessed the clinical toxicity in 97% of the
      patients. Patients carrying variant alleles of ABCB1 C3435T experienced more
      pronounced neutrophil decrease (63%, 72% and 80% for 3435CC, CT and TT,
      respectively; p-value 0.03). A similar association was found for G2677T/A, p
      value 0.02. For C1236T, there was a trend with p-value 0.06. No statistically
      significant correlations were found for paclitaxel compliance and sensory
      neuropathy in the primary analysis. Variants in the drug transporter ABCB1 gene
      are possibly associated with the neutrophil suppressing effect of paclitaxel in
      patients with ovarian cancer. This finding has implications for the understanding
      of bone marrow suppression and future tailored chemotherapy. 

PMID- 21955856
TI  - Community-owned resource persons for malaria vector control: enabling factors and
      challenges in an operational programme in Dar es Salaam, United Republic of
      Tanzania.
AB  - BACKGROUND: Community participation in vector control and health services in
      general is of great interest to public health practitioners in developing
      countries, but remains complex and poorly understood. The Urban Malaria Control
      Program (UMCP) in Dar es Salaam, United Republic of Tanzania, implements larval
      control of malaria vector mosquitoes. The UMCP delegates responsibility for
      routine mosquito control and surveillance to community-owned resource persons
      (CORPs), recruited from within local communities via the elected local
      government. METHODS: A mixed method, cross-sectional survey assessed the ability
      of CORPs to detect mosquito breeding sites and larvae, and investigated
      demographic characteristics of the CORPs, their reasons for participating in the
      UMCP, and their work performance. Detection coverage was estimated as the
      proportion of wet habitats found by the investigator which had been reported by
      CORP. Detection sensitivity was estimated as the proportion of wet habitats found
      by the CORPS which the investigator found to contain Anopheles larvae that were
      also reported to be occupied by the CORP. RESULTS: The CORPs themselves perceived
      their role as professional rather than voluntary, with participation being a de
      facto form of employment. Habitat detection coverage was lower among CORPs that
      were recruited through the program administrative staff, compared to CORPs
      recruited by local government officials or health committees (Odds Ratio = 0.660,
      95% confidence interval = [0.438, 0.995], P = 0.047). Staff living within their
      areas of responsibility had > 70% higher detection sensitivity for both
      Anopheline (P = 0.016) and Culicine (P = 0.012): positive habitats compared to
      those living outside those same areas. DISCUSSION AND CONCLUSIONS: Improved
      employment conditions as well as involving the local health committees in
      recruiting individual program staff, communication and community engagement
      skills are required to optimize achieving effective community participation,
      particularly to improve access to fenced compounds. A simpler, more direct, less
      extensive community-based surveillance system in the hands of a few, less
      burdened, better paid and maintained program personnel may improve performance
      and data quality.

PMID- 21955857
TI  - Comprehensive comparison of three commercial human whole-exome capture platforms.
AB  - BACKGROUND: Exome sequencing, which allows the global analysis of protein coding
      sequences in the human genome, has become an effective and affordable approach to
      detecting causative genetic mutations in diseases. Currently, there are several
      commercial human exome capture platforms; however, the relative performances of
      these have not been characterized sufficiently to know which is best for a
      particular study. RESULTS: We comprehensively compared three platforms:
      NimbleGen's Sequence Capture Array and SeqCap EZ, and Agilent's SureSelect. We
      assessed their performance in a variety of ways, including number of genes
      covered and capture efficacy. Differences that may impact on the choice of
      platform were that Agilent SureSelect covered approximately 1,100 more genes,
      while NimbleGen provided better flanking sequence capture. Although all three
      platforms achieved similar capture specificity of targeted regions, the NimbleGen
      platforms showed better uniformity of coverage and greater genotype sensitivity
      at 30- to 100-fold sequencing depth. All three platforms showed similar power in
      exome SNP calling, including medically relevant SNPs. Compared with genotyping
      and whole-genome sequencing data, the three platforms achieved a similar accuracy
      of genotype assignment and SNP detection. Importantly, all three platforms showed
      similar levels of reproducibility, GC bias and reference allele bias.
      CONCLUSIONS: We demonstrate key differences between the three platforms,
      particularly advantages of solutions over array capture and the importance of a
      large gene target set.

PMID- 21955858
TI  - Prenatal attachment and associated factors during the third trimester of
      pregnancy in Temuco, Chile.
AB  - OBJECTIVE: to estimate the prevalence of poorer prenatal attachment and its
      association with psycho-affective factors in pregnant women during the third
      trimester. DESIGN AND SETTING: cross-sectional study in Temuco, La Araucania
      Region, Chile. MEASUREMENTS: data were collected by structured interview with
      closed questions for the sociodemographic characterisation of the sample and
      measurement of six aspects: prenatal attachment, perceived stress, depression,
      perception of relationship with partner, subjective family support, and obstetric
      information regarding current and previous pregnancies. PARTICIPANTS: 244
      pregnant women selected by stratified random sampling in all centres (n=5) of the
      public health system in Temuco, Chile, with proportional allocation. FINDINGS:
      the prevalence of poorer prenatal attachment was 24.3% (95% confidence interval
      19-30%), and this was found to be associated with discontent with the pregnancy,
      unwanted pregnancy, higher levels of perceived stress, depression and low family
      support. Religious activity and work were found to modulate the association
      between poorer prenatal attachment and psycho-affective aspects. The percentage
      of unplanned pregnancies was high in this study (61.35), and although this does
      not have a direct influence on poorer prenatal attachment, it is associated with
      discontent with the pregnancy and unwanted pregnancy. KEY CONCLUSIONS AND
      IMPLICATIONS FOR PRACTICE: the high proportion of poorer prenatal attachment
      during the third trimester of pregnancy associated with potentially detectable
      psychosocial factors means that early diagnosis and timely intervention during
      prenatal care are an essential challenge for midwives in their work. Any progress
      that can be made during pregnancy will favour the development of the bonding
      experience after birth, and thus the balanced development of the child.

PMID- 21955859
TI  - Autoimmune cholangitis mimicking a klatskin tumor: a case report.
AB  - INTRODUCTION: Autoimmune cholangitis remains an elusive manifestation of
      immunoglobulin G4-associated systemic disease most commonly encountered in
      patients with autoimmune pancreatitis. No strict diagnostic criteria have been
      described to date and diagnosis mainly relies on a combination of clinical and
      histopathologic findings. It is hence even more challenging to diagnose
      autoimmune cholangitis in patients with late or atypical presentations, such as
      without concomitant pancreatic involvement. Early diagnosis of this rare disorder
      can significantly improve outcomes considering high rates of surgical
      intervention, as well as high relapse rates in the absence of steroid treatment.
      To the best of our knowledge the literature is quite sparse on cases with
      atypical presentations of autoimmune cholangitis. CASE PRESENTATION: We report a
      case of a previously healthy 65-year-old man of Middle-Eastern origin, with a
      history of pancreatic insufficiency of unknown etiology, evaluated for elevated
      liver function tests found incidentally on a routine physical examination.
      Imaging studies revealed an atrophic pancreas and biliary duct dilatation
      consistent with obstruction. Subsequent endoscopic retrograde
      cholangiopancreatography showed a bile duct narrowing pattern suggestive of
      cholangiocarcinoma, but brushings failed to reveal malignant cells. Our patient
      proceeded to undergo surgical resection. Histological examination of the resected
      mass revealed lymphoplasmacytic infiltrate with no malignant features. Our
      patient returned three months later with persistently high liver function tests
      and no evidence of biliary obstruction on imaging. A presumptive diagnosis of
      autoimmune cholangitis was made and our patient's symptoms resolved after a short
      course of an oral steroid regimen. Post factum staining of the resection specimen
      revealed an immunoglobulin G4 antibody positive immune cell infiltrate,
      consistent with the proposed diagnosis. CONCLUSION: Our case thus highlights the
      importance of clinician awareness of the autoimmune spectrum of biliary
      pathologies when confronted with atypical clinical presentations, the paucity of
      diagnostic measures and the benefit from long-term steroid and/or
      immunosuppressive treatment.

PMID- 21955860
TI  - Effect of cinacalcet on bone mineral density of the radius in hemodialysis
      patients with secondary hyperparathyroidism.
AB  - BACKGROUND/AIM: Cinacalcet, an allosteric modulator of the calcium sensing
      receptor, effectively reduces serum parathyroid hormone (PTH) in patients with
      secondary hyperparathyroidism. It is not well known whether bone mineral density
      (BMD) of hemodialysis patients with secondary hyperparathyroidism is altered
      after cinacalcet treatment. METHODS: The BMD in the distal 1/3 of the radius and
      in the ultradistal radius, which are enriched with cortical and cancellous bone,
      respectively, was examined by dual X-ray absorptiometry, 1 year prior to, at the
      start, and 1 year after cinacalcet treatment, in 61 patients. RESULTS: The BMD of
      both the distal 1/3 and ultradistal radius decreased significantly in the year
      prior to cinacalcet treatment (p < 0.01). However, the BMD at either site did not
      change significantly in the year after cinacalcet treatment. The annual changes
      in the BMD of the distal 1/3 radius increased significantly from -0.023 +/- 0.029
      g/cm2/year to -0.002 +/- 0.033 g/cm2/year, prior to and after cinacalcet
      treatment, respectively; however, the annual changes in the BMD of the
      ultradistal radius did not change significantly prior to and after cinacalcet
      treatment. CONCLUSION: There was a significant association between cinacalcet
      treatment and reduction in BMD loss in patients with secondary
      hyperparathyroidism. Cortical bone, rather than cancellous bone, was particularly
      affected by cinacalcet treatment.

PMID- 21955861
TI  - A study of maintenance therapy after intravenous maxacalcitol for secondary
      hyperparathyroidism.
AB  - AIM: Intravenous vitamin D therapy is an established treatment for secondary
      hyperparathyroidism (SHPT). However, no protocols have been established for
      maintenance therapy with intravenous or oral vitamin D after control of intact
      parathyroid hormone (iPTH) within the target range. METHODS: Step I. For patients
      with SHPT (200 <= iPTH <= 500 pg/ml), a dose of 2.5 mg maxacalcitol (OCT) was
      administered intravenously three times a week with oral sevelamer hydrochloride;
      the dose was increased to a 10 ug maximum three times a week to control iPTH to <
      150 pg/ml. Step II. When iPTH reached the target level, patients were assigned to
      Group A (oral alfacalcidol 1.0 ug/day) or B (oral alfacalcidol 0.25 ug/ day).
      Serum iPTH, calcium, and inorganic phosphorus were measured each month for 6
      months. Maintenance rates for the target iPTH levels were evaluated, < 150 pg/ml
      at Step I and < 200 pg/ml at Step II. RESULTS: iPTH decreased to < 150 pg/ml by
      OCT in 24 of 35 patients (68.6%). During the 24-week observation period, iPTH was
      controlled for 83.3% patients in Group A vs. 36.4% for Group B (p < 0.05). No
      dropouts due to hypercalcemia or hyperphosphatemia occurred. CONCLUSION: OCT dose
      titration was effective for SHPT. A higher daily dose of oral alfacalcidol (1.0
      ug) appears to be more effective than a lower dose (0.25 ug) as maintenance
      therapy after iPTH control.

PMID- 21955862
TI  - ACEI and ARB combination therapy in patients with macroalbuminuric diabetic
      nephropathy and low socioeconomic level: a double-blind randomized clinical
      trial.
AB  - OBJECTIVE: The combination of an ACE inhibitor (ACEI) and an angiotensin II
      receptor blocker (ARB) has been proposed for the treatment of diabetic
      nephropathy (DN), but doubts remain about its efficacy and safety. We compared
      the effects of combination therapy and ACEI monotherapy on proteinuria and on
      three urinary inflammatory cytokines (MCP-1, TGF-beta and VEGF). DESIGN AND
      PATIENTS: 56 patients with macroalbuminuric DN received 40 mg/d enalapril for 4
      months, followed by add-on 100 mg/day losartan or placebo for another 4 months.
      The primary and secondary endpoints were reduction of proteinuria and cytokine
      levels, respectively. RESULTS: Proteinuria did not fall in either group. Repeated
      measures ANOVA revealed no difference between groups. A high side effect rate was
      observed (28.5%). Finally, unadjusted logistic regression showed no difference
      between groups, but after adjustments the risk of worsening proteinuria was
      higher in the combination therapy group (p = 0.04). The same pattern was observed
      for urinary MCP- 1. CONCLUSION: These results suggest that 1) in advanced DN with
      severe proteinuria and poor metabolic control, angiotensin II blockade may be
      less effective than in other groups of CKD patients. 2) In such patients,
      combination therapy may not afford superior renoprotection compared to enalapril.
      3) Urinary MCP-1 is a promising biomarker for the response to ACEI and/or ARB
      treatment and for the risk of associated unwanted effects.

PMID- 21955863
TI  - Serum accumulation of a creatinine oxidative metabolite (NZ-419: 5-hydroxy-1-
      methylhydatoin) as an intrinsic antioxidant in diabetic patients with or without
      chronic kidney disease.
AB  - AIMS: In mammals, creatinine (Cr) is catabolized by a dual oxidative pathway via
      5-hydroxy-1-methylhydantoin or 5-hydroxycreatinine. The former, an intrinsic
      antioxidant, termed NZ-419, has been reported to prevent the progression of
      chronic renal failure in animal models. However, its clinical intrinsic serum
      level has not yet been reported. METHODS: We analyzed serum NZ-419 levels in
      diabetic and nondiabetic patients with or without Stage 3 - 5 chronic kidney
      disease (CKD). RESULTS: The levels of NZ-419 in diabetic patients with (88.1 +/-
      17.2 ug/dl, p < 0.001) or without (31.5 +/- 2.4 ug/dl, p < 0.05) Stage 3 - 5 CKD
      were significantly higher than in nondiabetic normal controls (9.0 +/- 5.6
      ug/dl). The molar ratio data showed NZ-419/Cr was significantly higher in both
      diabetic patients with (p < 0.01) or without Stage 3 - 5 CKD (p < 0.001) compared
      to nondiabetic normal controls. No further increase occurred with increasing
      severity of renal failure. Furthermore, nondiabetic patients with or without
      Stage 3 - 5 CKD did not show significantly different molar ratio values than
      controls but had significantly higher values of NZ-419 levels (p < 0.001).
      CONCLUSIONS: Overproduction and decreased clearance played a major role in the
      increased NZ-419 levels we observed in the patients with diabetes and Stage 3 - 5
      CKD, respectively. The existence of chronic renal failure did not further enhance
      this overproduction.

PMID- 21955864
TI  - Carotid intima-media thickness and cerebral white matter lesions are more
      advanced in acute ischemic stroke patients with renal dysfunction.
AB  - BACKGROUND: It has been shown that chronic kidney disease (CKD) is a risk factor
      for stroke, but there have been few studies on the relationship between CKD and
      stroke. The objective of this study was to investigate the relationship between
      renal dysfunction and cerebral white matter lesions or carotid plaque in patients
      with acute ischemic stroke. METHODS: Subjects were 202 consecutive patients with
      ischemic stroke who were admitted to the Stroke Center of Nippon Medical School
      Hospital from January 2007 to July 2008. The estimated glomerular filtration
      (eGFR) was calculated and the relationship of renal dysfunction to the subtype of
      ischemic stroke, cardiovascular risk factors, cerebral white matter lesions on
      brain magnetic resonance imaging (MRI), and maximum intima-media thickness (IMT)
      of the carotid artery was analyzed statistically. RESULTS: Among the 202 patients
      with ischemic stroke, 27.9% had an eGFR < 60 ml/min/1.73 m2 (eGFR < 60 ml group).
      Age was significantly higher and a history of hypertension, diabetes, and
      ischemic heart disease was significantly more frequent in this group than in the
      group with eGFR >= 60 ml/min/1.73 m2 (eGFR >= 60 ml group). Among the subtypes of
      ischemic stroke, atherothrombotic cerebral infarction was predominant and
      accounted for 41.1%, followed by cardiogenic cerebral infarction at 31.1%,
      lacunar infarction at 18.8%, and unclassified infarction at 8.9%. There was no
      significant difference in the distribution of ischemic stroke subtype between
      both groups. Deep and subcortical white matter hypertensity (DSWMH) and
      periventricular hyperintensity (PVH) were detected by brain MRI in 91.5% of the
      eGFR < 60 ml group. In the eGFR < 60 ml group, PVH was significantly more
      frequent than in the eGFR >= 60 ml group (p = 0.032) and DSWMH was also more
      frequent (p = 0.0519). The maximum IMT measured by carotid ultrasound was
      significantly larger in the eGFR < 60 ml group. CONCLUSION: In patients with
      acute ischemic stroke, the incidence of renal dysfunction was high like that of
      heart disease. In the eGFR < 60 ml group, carotid IMT was larger and the
      incidence of PVH was higher, so these patients presumably had more advanced
      atherosclerotic changes of the cerebral vessels.

PMID- 21955865
TI  - Distribution of reference GFR in a development population: a critical factor for
      the establishment of a GFR estimation equation.
AB  - BACKGROUND AND AIM: Our previous work showed that the performance of MDRD
      equations could be improved by modifying the original MDRD equation. However,
      during the modification we recognized that reference GFR (rGFR) distribution was
      not similar between the MDRD study and the Chinese Estimating GFR (eGFR)
      Investigation Study. This present study was designed to illustrate that the GFR
      estimating equation might be influenced by the difference of rGFR distribution in
      the development population. Racial factors might not be as important as once
      thought. PATIENTS AND METHODS: The Chinese eGFR Investigation Study dataset
      containing 684 CKD patients was defined as Dataset I, the modified MDRD equation
      for Chinese was defined as Equation 1. Datasets II and III were generated
      respectively by deleting 125 cases of CKD Stage 1 from Dataset I and by adding
      297 cases of apparently healthy Chinese adults into Dataset I. eGFR was estimated
      using Equation 1. Using rGFR as dependent and eGFR as independent, linear
      regression models were constructed using Dataset II and Dataset III,
      respectively, and generated Equation 2 and Equation 3. The prevalence of eGFR
      less than 60 ml/min/1.73 m2 in the adult Beijing population was calculated using
      Equation 1, 2 and 3. RESULTS: The previous reported prevalence of decreased GFR
      using Equation 1 in the Beijing adult population was 1.3% (0.8 - 1.8). By using
      Equation 2 and Equation 3, the prevalence increased to 3.2% (2.49 - 4.13) and
      decreased to 0.8% (0.57 - 1.28), respectively. CONCLUSIONS: GFR estimating
      equation was influenced by rGFR distribution of the development dataset.

PMID- 21955866
TI  - Outcome of peritoneal dialysis in cirrhotic patients with end-stage renal
      disease: a 24-years' experience in Taiwan.
AB  - BACKGROUND: Use of peritoneal dialysis (PD) in liver cirrhosis patients with end
      stage renal disease remains controversial. Moreover, the long-term outcome in
      cirrhotic patients is unclear. The aim of the present study was to analyze the
      outcome of cirrhotic patients treated with PD in our center during the past 24
      years. METHODS: We retrospectively reviewed the data of cirrhotic patients who
      received PD between 1984 and 2009. A group of noncirrhotic patients who were age-
      and sex-matched during the same period were selected as controls. Peritonitis
      rates, complications and outcomes were compared. RESULTS: A total of 30 cirrhotic
      patients and 60 control patients were included in the analysis. Peritonitis-free
      survival did not differ between groups. Gram-positive organisms, especially
      coagulase-negative staphylococcus and streptococcus sp., were the major causes of
      peritonitis in the cirrhotic patients. Also in the cirrhotic patients,
      complications such as umbilical hernia, chronic hypotension and erythropoietin
      resistance were more common as compared with controls. An initially higher solute
      and water transport capacity was observed in the cirrhotic patients, which became
      comparable to controls by the end of the 2nd year of treatment. Serum albumin
      concentrations were lower in cirrhotic patients (p = 0.01), and the decline of
      renal Kt/V was slower in cirrhotic patients as compared to that of controls (p <
      0.0001). There was no significant difference in patient and technique survival
      between the two groups. CONCLUSION: Our study suggests that PD is an effective
      therapy with a comparable risk of peritonitis and solute clearance in liver
      cirrhosis patients with end-stage renal failure.

PMID- 21955867
TI  - Effects of conventional versus biocompatible peritoneal dialysis solutions on
      peritoneal and systemic inflammation, malnutrition and atherosclerosis in CAPD
      patients.
AB  - BACKGROUND: Chronic inflammation, malnutrition and atherosclerosis (MIA syndrome)
      are important predictors of high mortality in continuous ambulatory peritoneal
      dialysis (CAPD) patients. We aimed to evaluate the effects of PD solutions
      (standard vs. biocompatible) on some parameters of MIA syndrome in patients
      undergoing CAPD. METHODS: 42 stable patients who were on CAPD at least 2.5 years
      participated in this cross-sectional study. Patients who had severe anemia (Hb <
      10 g/l), immunomodulatory therapy, peritonitis or any inflammatory conditions for
      at least 3 months before the analysis, malignant disease and acute exacerbation
      of heart failure, were excluded. 21 (50%) patients were treated with standard PD
      solutions (CAPDP-1), while the remaining 21 (50% of patients) were treated with
      biocompatible PD solutions (neutral solutions with lower level of glucose
      degradation products and lower concentration of calcium, CAPDP-2). All patients
      underwent echocardiography and B-mode ultrasonography of common carotid arteries
      together with assessments of nutrition status and parameters of systemic and
      local inflammation. RESULTS: There were no significant differences between the
      groups concerning age, gender, underlying disease, residual renal function,
      peritoneal transport characteristics, comorbidity or therapy applied. Patients
      from group CAPDP-2 had a significantly lower serum level of hs-CRP (3.7 +/- 2.6
      mg/l vs. 6.3 +/- 4.5 mg/l; p = 0.023) and significantly better nutritional status
      confirmed by mid-arm circumference (p = 0.015), mid-arm muscle circumference (p =
      0.002) and subjective global assessment (14.28% of patients in CAPDP-2 vs. 71% of
      patients in CAPDP-1 were malnourished; p = 0.000). Group CAPD-2 had less frequent
      left ventricular hypertrophy (p = 0.039), thinner intima-media thickness (p =
      0.005), smaller carotid narrowing (p = 0.000) and fewer calcified plaques of
      common carotide arteries (p = 0.003). No significant difference between the CAPDP
      groups was observed in serum and effluent levels of inflammatory cytokines (IL-1,
      IL-6 and TNF-alpha) and CA-125 effluent level. Logistic regression analysis did
      not confirm that biocompatibility of PD solutions was an independent predictor of
      any parameter of MIA syndrome. CONCLUSIONS: According to the present study and
      logistic regression analysis, the effect of biocompatible CAPD solutions on
      parameters of malnutrition, inflammation and atherosclerosis have to be confirmed
      by well-designed and controlled studies in a higher number of patients.

PMID- 21955868
TI  - Lecithin-cholesterol acyltransferase (LCAT) deficiency without mutations in the
      coding sequence: a case report and literature review.
AB  - Familial lecithin-cholesterol acyltransferase (LCAT) deficiency (FLD) is a rare
      genetic disease characterized by corneal opacities, normocytic anemia,
      dyslipidemia, and proteinuria progressing to chronic renal failure. In all FLD
      cases, a mutation has been found in the coding sequence of the LCAT gene. FLD is
      clinically distinguished from an acquired form of LCAT deficiency by the presence
      of corneal opacities. Here we describe a 36-year-old woman presenting with
      clinical, pathological, and laboratory data compatible with FLD. Her mother and
      elder sister had corneal opacities. However, genetic analysis revealed there were
      no mutations in the LCAT coding sequences and no alterations in LCAT mRNA
      expression. Furthermore, we were unable to find any underlying conditions that
      may lead to LCAT deficiency. The present case therefore demonstrates that LCAT
      deficiency may be caused by factors other than mutations in the coding sequence
      and we suggest that a translational or posttranslational mechanism may be
      involved.

PMID- 21955869
TI  - Young woman with branchio-oto-renal syndrome and a novel mutation in the EYA-1
      gene.
AB  - Branchio-oto-renal (BOR) syndrome is an autosomal dominant disease clinically
      characterized by the coexistence of some or all of the following major disorders:
      deafness, cervical branchial fistulae, preauricular pits, and renal
      abnormalities. Most families with BOR syndrome have mutations on the EYA-1 gene
      on chromosome 8q. We present the case of a 23-year-old Italian woman without a
      familial history of BOR syndrome. The patient, who had hearing loss and a history
      of surgeries for correction of bilateral cervical branchial fistulae and
      bilateral preauricular pits, presented with renal impairment, hypertension and
      overt proteinuria. DNA sequencing showed a novel heterozygous mutation 1420
      1421delCC in exon 14 of EYA-1 gene.

PMID- 21955870
TI  - Bilateral renal artery dissection following extreme exertion.
AB  - Dissection of a renal artery is rare and is usually associated with underlying
      arterial disease. Bilateral renal artery dissection following extreme exertion is
      exceptionally uncommon, and thus presents a diagnostic challenge. We report a
      case of a middle-aged, otherwise healthy man who presented to the hospital with
      left flank pain after a long bicycling trip. Initial laboratory tests and
      urinalysis were normal. Careful review of a contrast-enhanced computed tomography
      angiogram (CTA) with 3D reconstruction revealed bilateral segmental renal artery
      dissection and thrombosis with corresponding renal infarcts. He was treated
      medically and rapidly recovered.

PMID- 21955871
TI  - Identifying subtypes of dual alcohol and marijuana users: a methodological
      approach using cluster analysis.
AB  - Alcohol is the most common psychoactive substance used with marijuana. However,
      little is known about the potential impact of different levels of use of both
      alcohol and marijuana and their influence on risky behaviors, injuries and
      psychosocial functioning. A systematic approach to identifying patterns of
      alcohol and marijuana use associated with increased risks has not yet been
      identified in the literature. We report on the secondary analysis of data
      collected from a RCT conducted in a busy urban emergency department. Cluster
      analysis was performed on the patterns of past 30-day alcohol and marijuana use
      in two random subsamples N1=210 and N2=217. Four distinct subtypes of those who
      use both alcohol and marijuana were identified: (1) Daily Marijuana and Weekly
      Alcohol users; (2) Weekly Alcohol and Weekly Marijuana users; (3) Daily Alcohol
      and Daily Marijuana users; and (4) Daily Alcohol, Weekly Marijuana users. The
      four subtypes were replicated in both subsamples and examination of the external
      validity using ANOVA to determine cluster differences on psychosocial and
      behavioral variables confirmed the theoretical relevance of different patterns of
      alcohol and marijuana use. There were significantly different psychosocial
      negative consequences and related risky behaviors among subtypes. We found that
      Daily Alcohol and Daily Marijuana users are at the highest risk to experience
      more negative consequences and engage in a broader spectrum of risky behaviors
      related to both substances, than the other three types of alcohol and marijuana
      users.

PMID- 21955872
TI  - A procedure that differentiates unintentional from intentional overdose in opioid
      abusers.
AB  - OBJECTIVE: The purpose of this study is to develop a procedure for assessing
      unintentional overdose (OD) in opiate abusers that differentiates it from
      intentional OD, and provides reliable information about the incident. METHODS: A
      sample of 121 patients in a methadone maintenance program at an urban university
      hospital completed a baseline assessment. A total of 70 participants completed an
      identical assessment at least 14 days later. The ability of an OD item to
      differentiate unintentional OD from intentional OD was tested, as was the test
      retest reliability of questions assessing symptoms and treatment of OD. RESULTS:
      The procedure is reliable and differentiated unintentional OD from intentional
      OD. Questions assessing symptoms of OD were endorsed in almost every
      unintentional OD incident, although reliability was affected by loss of
      consciousness. The reliability of questions assessing emergency treatment and
      Narcan administration was outstanding. CONCLUSIONS: Our procedure for assessing
      OD differentiates unintentional OD from intentional OD. The use of follow-up
      questions assessing acute treatment for OD is recommended. Items concerning
      symptoms of OD are not needed to confirm the presence of an OD, but may be used
      to clarify whether an event was an OD.

PMID- 21955873
TI  - Web-based intervention for adolescent nonsmokers to help parents stop smoking: a
      pilot feasibility study.
AB  - A novel approach to tobacco control is to engage adolescent nonsmokers in support
      roles to encourage and help their parents stop smoking. This pilot study examined
      the feasibility and potential efficacy of a web-based support skills training
      (SST) intervention for adolescents to help a parent stop smoking. Forty
      nonsmoking adolescents 13-19 years of age (70% female, 93% White) were enrolled
      and randomly assigned to a health education (HE) control group (n=20) or SST
      (n=20). Both consisted of written materials and five weekly, 30 min, web-based,
      counselor-facilitated group sessions. Parents were enrolled for assessments only.
      Adolescents and parents completed assessments at baseline, week 6 (post
      treatment), week 12 and 6-months follow-up. Both interventions were feasible
      based on treatment acceptability ratings, study retention and treatment
      compliance. The biochemically confirmed 6-month smoking abstinence rate was
      higher for parents linked to teens in HE (35%, 7/20) than in SST (10%, 2/20),
      p=0.13. About half of parents in each group reported a quit attempt since study
      enrollment. Teens can be engaged to help parents stop smoking. Future research is
      warranted on determining effective intervention approaches.

PMID- 21955874
TI  - Personality and alcohol use: the role of impulsivity.
AB  - Research has shown that personality traits associated with impulsivity influence
      alcohol use during emerging adulthood, yet relatively few studies have examined
      how distinct facets of impulsivity are associated with alcohol use and abuse. We
      examine the influence of impulsivity traits on four patterns of alcohol use
      including frequency of alcohol use, alcohol-related problems, binge drinking, and
      alcohol use disorders (AUDs) in a community sample of young individuals (N=190).
      In multivariate regression analyses that controlled for peer and parental alcohol
      use, psychological distress, and developmental correlates (i.e., college,
      marriage, employment) in emerging adulthood, we found that urgency and sensation
      seeking were consistently related to all four constructs of alcohol use. The
      present study suggests that distinct impulsivity traits may play different roles
      in escalation of alcohol use and development of AUDs during emerging adulthood.

PMID- 21955875
TI  - Local synteny and codon usage contribute to asymmetric sequence divergence of
      Saccharomyces cerevisiae gene duplicates.
AB  - BACKGROUND: Duplicated genes frequently experience asymmetric rates of sequence
      evolution. Relaxed selective constraints and positive selection have both been
      invoked to explain the observation that one paralog within a gene-duplicate pair
      exhibits an accelerated rate of sequence evolution. In the majority of studies
      where asymmetric divergence has been established, there is no indication as to
      which gene copy, ancestral or derived, is evolving more rapidly. In this study we
      investigated the effect of local synteny (gene-neighborhood conservation) and
      codon usage on the sequence evolution of gene duplicates in the S. cerevisiae
      genome. We further distinguish the gene duplicates into those that originated
      from a whole-genome duplication (WGD) event (ohnologs) versus small-scale
      duplications (SSD) to determine if there exist any differences in their patterns
      of sequence evolution. RESULTS: For SSD pairs, the derived copy evolves faster
      than the ancestral copy. However, there is no relationship between rate asymmetry
      and synteny conservation (ancestral-like versus derived-like) in ohnologs. mRNA
      abundance and optimal codon usage as measured by the CAI is lower in the derived
      SSD copies relative to ancestral paralogs. Moreover, in the case of ohnologs, the
      faster-evolving copy has lower CAI and lowered expression. CONCLUSIONS: Together,
      these results suggest that relaxation of selection for codon usage and gene
      expression contribute to rate asymmetry in the evolution of duplicated genes and
      that in SSD pairs, the relaxation of selection stems from the loss of ancestral
      regulatory information in the derived copy.

PMID- 21955876
TI  - Biodegradation pathway and detoxification of the diazo dye Reactive Black 5 by
      Phanerochaete chrysosporium.
AB  - The in vivo biodegradation of the diazo dye Reactive Black 5 (RB5) by
      Phanerochaete chrysosporium immobilised on cubes of nylon sponge and on sunflower
      seed shells (SS) in laboratory-scale bioreactors was investigated. The SS
      cultivation led to the best results with a decolouration percentage of 90.3% in
      72 h for an initial RB5 concentration of 100 mg/L. It was found that the addition
      of 0.4 mM veratryl alcohol (VA) into the medium considerably increased the
      decolouration rate in SS cultivation. However, the addition of VA had no effect
      in the nylon cultivation. Thin layer chromatography (TLC) revealed that RB5 was
      transformed into one metabolite after 24 h. UV-vis spectroscopy and Fourier
      Transform Infrared (FT-IR) also confirmed the biodegradation of RB5. Toxicity of
      RB5 solutions before and after fungal treatment was assayed using Sinorhizobium
      meliloti as a sensitive soil microorganism. P. chrysosporium transformed the
      toxic dye RB5 into a non-toxic product.

PMID- 21955878
TI  - Biodiesel synthesis and conformation of lipase from Burkholderia cepacia in room
      temperature ionic liquids and organic solvents.
AB  - Biodiesel synthesis and conformation of Burkholderia cepacia lipase (BCL) were
      studied in 19 different room temperature ionic liquids (RTLLs) with a range of
      cation and anion structures. Overall, anion selection had a greater influence on
      biodiesel conversion than cation choice. RTILs containing Tf2N- and PF6- anions
      were suitable reaction media, while RTIL of [OmPy][BF4] was the best reaction
      medium with a biodiesel yield of 82.2+/-1.2%. RTILs with strong water miscible
      properties showed very low biodiesel yields. Conformational analysis by FT-IR
      revealed that higher biodiesel conversion in RTILs was correlated with a low
      tendency in alpha-helix content of BCL. An ultrasound-assisted biocatalysis
      process in RTILs was used to improve mass transfer rate, leading to 83% reduction
      of the reaction time for biodiesel production.

PMID- 21955877
TI  - Upflow bio-filter circuit (UBFC): biocatalyst microbial fuel cell (MFC)
      configuration and application to biodiesel wastewater treatment.
AB  - A biodiesel wastewater treatment technology was investigated for neutral
      alkalinity and COD removal by microbial fuel cell. An upflow bio-filter circuit
      (UBFC), a kind of biocatalyst MFC was renovated and reinvented. The developed
      system was combined with a pre-fermented (PF) and an influent adjusted (IA)
      procedure. The optimal conditions were operated with an organic loading rate
      (OLR) of 30.0 g COD/L-day, hydraulic retention time (HRT) of 1.04 day, maintained
      at pH level 6.5-7.5 and aerated at 2.0 L/min. An external resistance of circuit
      was set at 10 kOmega. The purposed process could improve the quality of the raw
      wastewater and obtained high efficiency of COD removal of 15.0 g COD/L-day.
      Moreover, the cost of UBFC system was only US$1775.7/m3 and the total power
      consumption was 0.152 kW/kg treated COD. The overall advantages of this invention
      are suitable for biodiesel wastewater treatment.

PMID- 21955879
TI  - Simultaneous saccharification and fermentation of Kanlow switchgrass by
      thermotolerant Kluyveromyces marxianus IMB3: the effect of enzyme loading,
      temperature and higher solid loadings.
AB  - Switchgrass (Panicum virgatum) was subjected to hydrothermolysis pretreatment and
      then used to study the effect of enzyme loading and temperature in a simultaneous
      saccharification and fermentation (SSF) with the thermotolerant yeast strain
      Kluyveromyces marxianus IMB3 at 8% solid loading. Various loadings of Accellerase
      1500 between 0.1 and 1.1 mL g(-1) glucan were tested in SSF at 45  degrees C
      (activity of enzyme was 82.2 FPU mL(-1)). The optimum enzyme loading was 0.7 mL
      g(-1) glucan based on the six different enzyme loadings tested. SSFs were
      performed at 37, 41 and 45  degrees C with an enzyme loading of 0.7 mL g(-1)
      glucan. The highest ethanol concentration of 22.5 g L(-1) was obtained after 168
      h with SSF at 45  degrees C, which was equivalent to 86% yield. Four different
      batch and fed-batch strategies were evaluated using a total solid loading of 12%
      (dry basis). About 32 g L(-1) ethanol was produced with the four strategies,
      which was equivalent to 82% yield.

PMID- 21955880
TI  - Improved production of the anticancer compound 1403C by glucose pulse feeding of
      marine Halorosellinia sp. (No. 1403) in submerged culture.
AB  - Effects of different pulse fed-batch methods on production of the anti-cancer
      compound 1403C by marine mangrove endophytic fungus Halorosellinia sp. (No. 1403)
      in a 5-L bioreactor were investigated. Since high glucose concentrations improved
      mycelial growth but inhibited 1403C production, the cultures were pulse fed with
      glucose solutions to keep the residual glucose lower than 4 g/L but higher than
      0.5 g/L during rapid growth phase (0-50 h). In this way, a maximum dry biomass,
      1403C production and yield coefficient (Y1403C/X) of up to 4.5 g/L, 2.64 g/L and
      0.59 g/g dry cell weight, respectively were achieved. These values are 22.7%,
      98.0% and 61.4%, respectively higher than those obtained with batch cultures.
      This strategy is valuable for fermentation scale-up of Halorosellinia sp. (No.
      1403) for 1403C production, and might also be applicable to other marine fungi
      cultures.

PMID- 21955881
TI  - Lipid accumulation and growth of Chlorella zofingiensis in flat plate
      photobioreactors outdoors.
AB  - Culturing microalgae using natural sunlight is an effective way to reduce the
      cost of microalgae-based biodiesel production. In order to evaluate the
      feasibility of culturing Chlorella zofingiensis outdoors for biodiesel
      production, effects of nitrogen limitation and initial cell concentration on
      growth and lipid accumulation of this alga were investigated in 60 L flat plate
      photobioreactors outdoors. The highest MUmax and biomass productivity obtained
      was 0.994 day(-1) and 58.4 mg L(-1)day(-1), respectively. The lipid content was
      much higher (54.5% of dry weight) under nitrogen limiting condition than under
      nitrogen sufficient condition (27.3%). With the increasing initial cell
      concentrations, the lipid contents declined, while lipid concentrations and
      productivities increased. The highest lipid content, lipid concentration, and
      lipid productivity obtained was 54.5%, 536 mg L(-1) and 22.3 mg L(-1)day(-1),
      respectively. This study demonstrated that it was possible to culture C.
      zofingiensis under outdoor conditions for producing biodiesel feedstock.

PMID- 21955882
TI  - Population level determinants of acute mountain sickness among young men: a
      retrospective study.
AB  - BACKGROUND: Many visitors, including military troops, who enter highland regions
      from low altitude areas may suffer from acute mountain sickness (AMS), which
      negatively impacts workable man-hours and increases healthcare costs. The aim of
      this study was to evaluate the population level risk factors and build a
      multivariate model, which might be applicable to reduce the effects of AMS on
      Chinese young men traveling to this region. METHODS: Chinese highland military
      medical records were used to obtain data of young men (n = 3727) who entered the
      Tibet plateau between the years of 2006-2009. The relationship between AMS and
      travel profile, demographic characteristics, and health behaviors were evaluated
      by logistic regression. Univariate logistic models estimated the crude odds
      ratio. The variables that showed significance in the univariate model were
      included in a multivariate model to derive adjusted odds ratios and build the
      final model. Data corresponding to odd and even years (2 subsets) were analyzed
      separately and used in a simple cross-validation. RESULTS: Univariate analysis
      indicated that travel profile, prophylactic use, ethnicity, and province of birth
      were all associated with AMS in both subsets. In multivariate analysis, young men
      who traveled from lower altitude (600-800 m vs. 1300-1500 m, adjusted odds ratio
      (AOR) = 1.32-1.44) to higher altitudes (4100-4300 m vs. 2900-3100 m, AOR = 3.94
      4.12; 3600-3700 m vs. 2900-3100 m, AOR = 2.71-2.74) by air or rapid land
      transport for emergency mission deployment (emergency land deployment vs. normal
      land deployment, AOR = 2.08-2.11; normal air deployment vs. normal land
      deployment, AOR = 2.00-2.20; emergency air deployment vs. normal land deployment,
      AOR = 2.40-3.34) during the cold season (cold vs. warm, AOR = 1.25-1.28) are at
      great risk for developing AMS. Non-Tibetan male soldiers (Tibetan vs. Han, AOR =
      0.03-0.08), born and raised in lower provinces (eastern vs. northwestern, AOR =
      1.32-1.39), and deployed without prophylaxis (prophylactic drug vs. none, AOR =
      0.75-0.76), also represented a population at significantly increased risk for
      AMS. The predicted model was built; the area under receiver operating
      characteristic curve was 0.703. CONCLUSION: Before a group of young men first
      enter a high altitude area, it is important that a health service plan should be
      made referring to the group's travel profile and with respect to young men's
      ethnicity and province of birth. Low-cost Chinese traditional prophylactic drugs
      might have some effect on decreasing the risk of AMS, although this needs further
      verification.

PMID- 21955883
TI  - Circulating levels of bisphenol A (BPA) and phthalates in an elderly population
      in Sweden, based on the Prospective Investigation of the Vasculature in Uppsala
      Seniors (PIVUS).
AB  - The plastic manufacture compounds, bisphenol A (BPA) and phthalates, are
      ubiquitous and have therefore been detected in virtually all types of analyzed
      human samples. The aim of this study was: (1) to investigate concentrations of
      serum levels of BPA and phthalate metabolites in seniors residing in the city of
      Uppsala, Sweden (2) to evaluate gender differences in relation to serum levels of
      BPA and phthalate metabolites in the subjects. In the population-based
      Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS),
      encompassing 1016 subjects, all aged 70, serum levels of BPA and phthalate
      metabolites were measured by Isotope Dilution-High Performance Liquid
      Chromatography-Tandem Mass Spectrometry. BPA and four out of ten phthalate
      metabolites, namely, Monoisobutyl phthalate (MiBP), Monomethyl phthalate (MMP),
      Monoethyl phthalate (MEP), Mono-(2-ethylhexyl) phthalate (MEHP), were detectable
      in almost all subjects. Of the remaining phthalate metabolites, Monobenzyl
      phthalate (MBzP), Mono-(2-ethyl-5-hydroxyhexyl) phthalate (MeHHP), and Mono-(2
      ethyl-5-oxohexyl) phthalate (MEOHP) were seen in some 300-700 of the subjects,
      whereas Monoisononyl phthalate (MINP) and Mono-n-octyl phthalate (MOP) were found
      in only a few and Monocyclohexyl phthalate (MCHP) was not detected in any
      subject. Neither the circulation levels of BPA nor those of phthalate metabolites
      differ between the genders in this elderly population of residents in Uppsala,
      Sweden.

PMID- 21955884
TI  - Evaluation of the sensitivity of genotoxicity and cytotoxicity endpoints in
      earthworms exposed in situ to uranium mining wastes.
AB  - Earthworms were exposed for 56 days to a contaminated soil from an abandoned
      uranium mine and to the natural reference soil LUFA 2.2. The exposure occurred in
      situ: the containers with contaminated soil were placed near the mine pit; the
      containers with reference soil were placed in a reference site. For the
      assessment of metals bioaccumulation, DNA damages, cell-to-cell variation in DNA
      content, Median Fluorescence Intensity (MFI), coelomocytes frequency and
      proliferation, organisms were sampled after 0, 1, 2, 7, 14 and 56 days of
      exposure. For the assessment of radionuclides bioaccumulation, animals were
      sampled after 0, 14 and 56 days of exposure. As for growth, organisms were
      sampled after 0, 14, 28 and 56 days of exposure. The reproduction assay was
      performed according to the OECD (2004) guideline. DNA damages were assessed by
      comet assay and flow cytometry was used to determine cell-to-cell variation in
      DNA content, Median Fluorescence Intensity (MFI), coelomocytes frequency and
      proliferation. Results have shown a myriad of effects in the organisms exposed to
      the contaminated soil, namely: the inhibition of reproduction, growth reduction,
      DNA damages, cytotoxicity, changes in eleocytes fluorescence intensity,
      coelomocytes proliferation and bioaccumulation of metals and radionuclides. Our
      results showed that the evaluation of genotoxicity and cytotoxicity endpoints,
      along with other parameters at an individual level in standard reproduction
      assays conducted in situ, are important to improve the risk assessment process of
      areas contaminated with uranium and other radioactive mining wastes.

PMID- 21955885
TI  - Distribution of killer cell immunoglobulin-like receptor genes in Roma from
      Republic of Macedonia.
AB  - The aim of this study was to analyze Killer Ig-Like Receptor (KIR) gene
      polymorphisms in Roma people from Republic of Macedonia. The studied sample
      consists of 103 healthy unrelated individuals, aged 20-45 years. All individuals
      are of Roma origin, residents of different geographical regions (Gostivar,
      Skopje, and Kochani). The population genetics analysis package, Arlequin, was
      used for analysis of the data. We found that all 16 KIR genes were observed in
      the Roma individuals and framework genes (KIR3DL3, KIR3DP1, KIR- 2DL4, and
      KIR3DL2) were present in all individuals. The frequencies of other KIR genes
      were: KIR2DP1 (1), KIR2DL1 (0.961), KIR2DL2 (0.544), KIR2DL3 (0.874), KIR2DL5
      (0.311), KIR3DL1 (0.990), KIR- 2DS1 (0.330), KIR2DS2 (0.553), KIR2DS3 (0.359),
      KIR2DS4 (0.981), KIR2DS5 (0.291), and KIR3DS1 (0.379). The results of tested
      linkage disequilibrium (LD) among KIR genes demonstrated that KIR genes present a
      wide range of linkage disequilibrium. The obtained results for KIR genes and
      genotype frequencies in Macedonian Roma individuals can be used for
      anthropological comparisons.

PMID- 21955886
TI  - GTPases in bacterial cell polarity and signalling.
AB  - In bacteria, large G domain GTPases have well-established functions in
      translation, protein translocation, tRNA modification and ribosome assembly. In
      addition, bacteria also contain small Ras-like GTPases consisting of stand-alone
      G domains. Recent data have revealed that small Ras-like GTPases as well as large
      G domain GTPases in bacteria function in the regulation of cell polarity, signal
      transduction and possibly also in cell division. The small Ras-like GTPase MglA
      together with its cognate GAP MglB regulates cell polarity in Myxococcus xanthus,
      and the small Ras-like GTPase CvnD9 in Streptomyces coelicolor is involved in
      signal transduction. Similarly, the large GTPase FlhF together with the ATPase
      FlhG regulates the localization and number of flagella in polarly flagellated
      bacteria. Moreover, large dynamin-like GTPases in bacteria may function in cell
      division. Thus, the function of GTPases in bacteria may be as pervasive as in
      eukaryotes.

PMID- 21955887
TI  - Mechanisms of immune evasion in fungal pathogens.
AB  - The incidence of life-threatening fungal infections has continued to increase in
      recent years, predominantly in patients debilitated by iatrogenic interventions
      or immunological dysfunctions. While the picture of the immunology of fungal
      infections grows increasingly complex, it is clear that the phagocyte-pathogen
      interaction is a critical determinant of establishing an infection. About 10
      years ago, genome-scale approaches began to elucidate the intricate and extensive
      fungal response to phagocytosis and in the last few years it has become clear
      that some of this response actively modulates immune cell function. Fungal
      pathogens avoid detection by masking pathogen-associated molecular patterns, such
      as cell wall carbohydrates, and by downregulating the complement cascade. Once
      detected, various species interfere with phagocytosis and intracellular
      trafficking, and can repress production of antimicrobials like nitric oxide (NO).
      For the most part, the molecular mechanisms behind these behaviors are not yet
      known. This review discusses recent discoveries and insights into how fungi
      manipulate the host-pathogen interaction.

PMID- 21955888
TI  - Protein dynamics and mechanisms controlling the rotational behaviour of the
      bacterial flagellar motor.
AB  - The proteins that make up the bacterial flagellar rotary motor have recently been
      shown to be more dynamic than previously thought, with some key proteins
      exchanging with pools of proteins in the membrane/cytoplasm. It has also become
      clear that in addition to simply switching in response to chemosensory signals,
      the rotation of the bacterial flagellar motor can be slowed or stopped, using a
      clutch or a brake, by signals from metabolism and growth state.

PMID- 21955889
TI  - Advocating broad-based knowledge.

PMID- 21955890
TI  - From 'front line' to 'core'.

PMID- 21955891
TI  - Higher education.

PMID- 21955892
TI  - Protecting whistleblowers.

PMID- 21955893
TI  - Social media.

PMID- 21955894
TI  - Leveling the research field through social media.

PMID- 21955895
TI  - Patient navigators improve colorectal cancer screening rates.

PMID- 21955896
TI  - Collaboration reduces pediatric adverse drug events.

PMID- 21955898
TI  - California mandated nurse-patient ratios deemed successful.

PMID- 21955900
TI  - Osteoarthritis: setting nursing's agenda.

PMID- 21955906
TI  - CE test 2.6 hours: deactivation of ICDs at the end of life: a systematic review
      of clinical practices and provider and patient attitudes.

PMID- 21955907
TI  - CE test 2.4 hours: preoperative fasting: will the evidence ever be put into
      practice?

PMID- 21955909
TI  - Supporting family caregivers: the hospital nurse's assessment of family caregiver
      needs.

PMID- 21955910
TI  - Treatment options for patients with kidney failure.

PMID- 21955911
TI  - When being good means looking bad.

PMID- 21955912
TI  - Medication calculation competency.

PMID- 21955913
TI  - Keeping secrets.

PMID- 21955914
TI  - Common characteristics of open source software development and applicability for
      drug discovery: a systematic review.
AB  - BACKGROUND: Innovation through an open source model has proven to be successful
      for software development. This success has led many to speculate if open source
      can be applied to other industries with similar success. We attempt to provide an
      understanding of open source software development characteristics for
      researchers, business leaders and government officials who may be interested in
      utilizing open source innovation in other contexts and with an emphasis on drug
      discovery. METHODS: A systematic review was performed by searching relevant,
      multidisciplinary databases to extract empirical research regarding the common
      characteristics and barriers of initiating and maintaining an open source
      software development project. RESULTS: Common characteristics to open source
      software development pertinent to open source drug discovery were extracted. The
      characteristics were then grouped into the areas of participant attraction,
      management of volunteers, control mechanisms, legal framework and physical
      constraints. Lastly, their applicability to drug discovery was examined.
      CONCLUSIONS: We believe that the open source model is viable for drug discovery,
      although it is unlikely that it will exactly follow the form used in software
      development. Hybrids will likely develop that suit the unique characteristics of
      drug discovery. We suggest potential motivations for organizations to join an
      open source drug discovery project. We also examine specific differences between
      software and medicines, specifically how the need for laboratories and physical
      goods will impact the model as well as the effect of patents.

PMID- 21955915
TI  - Biomechanical, psychosocial and individual risk factors predicting low back
      functional impairment among furniture distribution employees.
AB  - BACKGROUND: Biomechanical, psychosocial and individual risk factors for low back
      disorder have been studied extensively however few researchers have examined all
      three risk factors. The objective of this was to develop a low back disorder risk
      model in furniture distribution workers using biomechanical, psychosocial and
      individual risk factors. METHODS: This was a prospective study with a six month
      follow-up time. There were 454 subjects at 9 furniture distribution facilities
      enrolled in the study. Biomechanical exposure was evaluated using the American
      Conference of Governmental Industrial Hygienists (2001) lifting threshold limit
      values for low back injury risk. Psychosocial and individual risk factors were
      evaluated via questionnaires. Low back health functional status was measured
      using the lumbar motion monitor. Low back disorder cases were defined as a loss
      of low back functional performance of -0.14 or more. FINDINGS: There were 92
      cases of meaningful loss in low back functional performance and 185 non cases. A
      multivariate logistic regression model included baseline functional performance
      probability, facility, perceived workload, intermediated reach distance number of
      exertions above threshold limit values, job tenure manual material handling, and
      age combined to provide a model sensitivity of 68.5% and specificity of 71.9%.
      INTERPRETATION: The results of this study indicate which biomechanical,
      individual and psychosocial risk factors are important as well as how much of
      each risk factor is too much resulting in increased risk of low back disorder
      among furniture distribution workers.

PMID- 21955916
TI  - First somatic mutation of E2F1 in a critical DNA binding residue discovered in
      well-differentiated papillary mesothelioma of the peritoneum.
AB  - BACKGROUND: Well differentiated papillary mesothelioma of the peritoneum (WDPMP)
      is a rare variant of epithelial mesothelioma of low malignancy potential, usually
      found in women with no history of asbestos exposure. In this study, we perform
      the first exome sequencing of WDPMP. RESULTS: WDPMP exome sequencing reveals the
      first somatic mutation of E2F1, R166H, to be identified in human cancer. The
      location is in the evolutionarily conserved DNA binding domain and
      computationally predicted to be mutated in the critical contact point between
      E2F1 and its DNA target. We show that the R166H mutation abrogates E2F1's DNA
      binding ability and is associated with reduced activation of E2F1 downstream
      target genes. Mutant E2F1 proteins are also observed in higher quantities when
      compared with wild-type E2F1 protein levels and the mutant protein's resistance
      to degradation was found to be the cause of its accumulation within mutant over
      expressing cells. Cells over-expressing wild-type E2F1 show decreased
      proliferation compared to mutant over-expressing cells, but cell proliferation
      rates of mutant over-expressing cells were comparable to cells over-expressing
      the empty vector. CONCLUSIONS: The R166H mutation in E2F1 is shown to have a
      deleterious effect on its DNA binding ability as well as increasing its stability
      and subsequent accumulation in R166H mutant cells. Based on the results, two
      compatible theories can be formed: R166H mutation appears to allow for protein
      over-expression while minimizing the apoptotic consequence and the R166H mutation
      may behave similarly to SV40 large T antigen, inhibiting tumor suppressive
      functions of retinoblastoma protein 1.

PMID- 21955918
TI  - Rapid processing of emotional expressions without conscious awareness.
AB  - Rapid accurate categorization of the emotional state of our peers is of critical
      importance and as such many have proposed that facial expressions of emotion can
      be processed without conscious awareness. Typically, studies focus selectively on
      fearful expressions due to their evolutionary significance, leaving the
      subliminal processing of other facial expressions largely unexplored. Here, I
      investigated the time course of processing of 3 facial expressions (fearful,
      disgusted, and happy) plus an emotionally neutral face, during objectively
      unaware and aware perception. Participants completed the challenging "which
      expression?" task in response to briefly presented backward-masked expressive
      faces. Although participant's behavioral responses did not differentiate between
      the emotional content of the stimuli in the unaware condition, activity over
      frontal and occipitotemporal (OT) brain regions indicated an emotional modulation
      of the neuronal response. Over frontal regions this was driven by negative facial
      expressions and was present on all emotional trials independent of later
      categorization. Whereas the N170 component, recorded on lateral OT electrodes,
      was enhanced for all facial expressions but only on trials that would later be
      categorized as emotional. The results indicate that emotional faces, not only
      fearful, are processed without conscious awareness at an early stage and
      highlight the critical importance of considering categorization response when
      studying subliminal perception.

PMID- 21955917
TI  - IRS-2 Deficiency impairs NMDA receptor-dependent long-term potentiation.
AB  - The beneficial effects of insulin and insulin-like growth factor I on cognition
      have been documented in humans and animal models. Conversely, obesity,
      hyperinsulinemia, and diabetes increase the risk for neurodegenerative disorders
      including Alzheimer's disease (AD). However, the mechanisms by which insulin
      regulates synaptic plasticity are not well understood. Here, we report that
      complete disruption of insulin receptor substrate 2 (Irs2) in mice impairs long
      term potentiation (LTP) of synaptic transmission in the hippocampus. Basal
      synaptic transmission and paired-pulse facilitation were similar between the 2
      groups of mice. Induction of LTP by high-frequency conditioning tetanus did not
      activate postsynaptic N-methyl-D-aspartate (NMDA) receptors in hippocampus slices
      from Irs2(-/-) mice, although the expression of NR2A, NR2B, and PSD95 was
      equivalent to wild-type controls. Activation of Fyn, AKT, and MAPK in response to
      tetanus stimulation was defective in Irs2(-/-) mice. Interestingly, IRS2 was
      phosphorylated during induction of LTP in control mice, revealing a potential new
      component of the signaling machinery which modulates synaptic plasticity. Given
      that IRS2 expression is diminished in Type 2 diabetics as well as in AD patients,
      these data may reveal an explanation for the prevalence of cognitive decline in
      humans with metabolic disorders by providing a mechanistic link between insulin
      resistance and impaired synaptic transmission.

PMID- 21955919
TI  - D4 dopamine receptors modulate NR2B NMDA receptors and LTP in stratum oriens of
      hippocampal CA1.
AB  - Dopamine plays an important role in synaptic plasticity and learning and is
      involved in the pathogenesis of various neurological and psychiatric disorders.
      Here, we reveal staining of dopaminergic fibers in stratum oriens of the mouse
      hippocampal CA1 region, a finding that is consistent with earlier reports.
      Furthermore, we examined the effect of dopamine agonists on NMDAR-dependent early
      long-term potentiation (LTP) (40 min) during gamma-aminobutyric acid (GABA)(A)
      mediated blockade. LTP of the AMPA component was strongly reduced in stratum
      oriens but barely affected in stratum radiatum. This layer-specific effect was
      caused by D4 receptor activation, which augmented the inactivation of synaptic
      NMDAR-mediated currents (NMDA EPSCs) during LTP induction through a Ca(2+)
      dependent G-protein-independent mechanism. A similar dopaminergic modulation of
      both NMDA EPSCs and LTP was also observed in mice constitutively lacking NR2A but
      was absent in mice lacking NR2B in principal forebrain neurons. Together, these
      experiments strongly indicate that dopaminergic modulation of early LTP in
      stratum oriens occurs through NMDARs containing NR2B subunits via D4Rs. Thus, a
      dopamine hyperfunction in stratum oriens may result in NMDAR hypofunction that
      could affect both normal and pathological conditions.

PMID- 21955921
TI  - Connectivity-based subdivisions of the human right "temporoparietal junction
      area": evidence for different areas participating in different cortical networks.
AB  - Controversy surrounds the role of the temporoparietal junction (TPJ) area of the
      human brain. Although TPJ has been implicated both in reorienting of attention
      and social cognition, it is still unclear whether these functions have the same
      neural basis. Indeed, whether TPJ is a precisely identifiable cortical region or
      a cluster of subregions with separate functions is still a matter of debate.
      Here, we examined the structural and functional connectivity of TPJ, testing
      whether TPJ is a unitary area with a heterogeneous functional connectivity
      profile or a conglomerate of regions with distinctive connectivity. Diffusion
      weighted imaging tractrography-based parcellation identified 3 separate regions
      in TPJ. Resting-state functional connectivity was then used to establish which
      cortical networks each of these subregions participates in. A dorsal cluster in
      the middle part of the inferior parietal lobule showed resting-state functional
      connectivity with, among other areas, lateral anterior prefrontal cortex.
      Ventrally, an anterior TPJ cluster interacted with ventral prefrontal cortex and
      anterior insula, while a posterior TPJ cluster interacted with posterior
      cingulate, temporal pole, and anterior medial prefrontal cortex. These results
      indicate that TPJ can be subdivided into subregions on the basis of its
      structural and functional connectivity.

PMID- 21955920
TI  - Topographic Maps within Brodmann's Area 5 of macaque monkeys.
AB  - Brodmann's area 5 has traditionally included the rostral bank of the
      intraparietal sulcus (IPS) as well as posterior portions of the postcentral gyrus
      and medial wall. However, different portions of this large architectonic zone may
      serve different functions related to reaching and grasping behaviors. The current
      study used multiunit recording techniques in anesthetized macaque monkeys to
      survey a large extent of the rostral bank of the IPS so that hundreds of
      recording sites could be used to determine the functional subdivisions and
      topographic organization of cortical areas in this region. We identified a
      lateral area on the rostral IPS that we term area 5L. Area 5L contains neurons
      with receptive fields on mostly the shoulder, forelimb, and digits, with no
      apparent representation of other body parts. Thus, there is a large magnification
      of the forelimb. Receptive fields for neurons in this region often contain
      multiple joints of the forelimb or multiple digits, which results in imprecise
      topography or fractures in map organization. Our results provide the first
      overall topographic map of area 5L obtained in individual macaque monkeys and
      suggest that this region is distinct from more medial portions of the IPS.

PMID- 21955922
TI  - Non-small cell lung carcinoma in an adolescent manifested by acute paraplegia due
      to spinal metastases: a case report.
AB  - INTRODUCTION: Bronchial carcinomas in childhood and adolescence are extremely
      rare; only individual cases have been reported previously. CASE PRESENTATION: We
      report on a 16-year-old Caucasian German boy with non-small cell lung carcinoma
      (squamous cell non-small cell lung carcinoma) stage IV, T4N2M1, without epidermal
      growth factor receptor overexpression and/or mutation or k-ras mutation. He
      presented with paraplegia due to spinal metastases of the bronchial carcinoma. No
      familial predisposition or toxin exposure was identified. Treatment following
      adult protocols consisted of surgical intervention for spinal metastases, first
      line cisplatinum and gemcitabine, irradiation and second-line docetaxel. After a
      transient response our patient experienced disease progression and died about 10
      months later. CONCLUSION: Response and survival in our 16-year-old patient were
      similar to adult patients with stage IV non-small cell lung carcinoma.

PMID- 21955923
TI  - Role of Siglecs on the leucocytes during the process of the joint's inflammation
      in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is considered as an autoimmune disease that
      intermittently causes the chronic and acute inflammation of the patient's small
      joints which can destroy the tissues around the joints resulting in the
      limitation of the joint's function. In the synovium and synovia of the joints,
      the infiltration and/or phagocytosis of the different kinds of leucocytes were
      demonstrated according to the phases of the acute and chronic inflammation. Also,
      Siglecs (sialic acid binding Ig-like lectins) were reported on the leucocytes
      which can induce the active and inhibitory immune response by the specific
      binding with sialic acid on the conjugates including the sialylation of the
      immunoglobulin which has been reported there was striking increasing in the
      synovium and synovia of the small joints, also in the sera on RA cases. This
      hypothesis proposed Siglecs on the leucocytes which infiltrate into the joint's
      cavity and the increasing sialic acid conjugates might play a role during the
      acute and chronic inflammation on RA disease. It might be helpful to explain the
      mechanism of the different inflammation in different circumstances in the RA.

PMID- 21955925
TI  - IDH testing in diagnostic neuropathology: review and practical guideline article
      invited by the Euro-CNS research committee.
AB  - Isocitrate dehydrogenase 1 (IDH1) gene mutations, primarily of the R132H type,
      occur in approximately 60 - 90% of diffuse and anaplastic gliomas and secondary
      glioblastomas. IDH mutations in gliomas are associated with several clinically
      relevant parameters including patient age, histopathological diagnosis, combined
      1p/19q deletion, TP53 mutation, MGMT promoter hypermethylation and patient
      survival. Therefore, testing of the IDH status is relevant for diagnostic and
      prognostic considerations in primary brain tumors. IDH status can be assessed by
      immunohistochemistry or DNA-based methods including gene sequencing in the
      routine setting. Here, we review the relevance of IDH testing in diffuse gliomas
      and present practical instructions including detailed descriptions of procedures
      and protocols for diagnostic IDH testing using immunohistochemistry (for both
      automated and manual staining) and gene sequencing. Our article may provide
      guidance for laboratories aiming at establishing IDH testing for diagnostic
      evaluation of primary brain tumors.

PMID- 21955926
TI  - Diagnostic utility of IDH1- and p53-mutation analysis in secondary gliosarcoma.
AB  - We report on a 47-year-old woman in whom an anaplastic astrocytoma was resected
      in 2006. Postoperative radiation had to be interrupted because of a wound
      infection necessitating explantation of the infected bone flap and implantation
      of a titanium mesh. Subsequently, radiation therapy was completed and
      temozolomide was administered for 45 cycles. In the beginning of 2010 a new
      contrast enhancing mass was seen in the former tumor region. The mass was
      subtotally excised and showed no histomorphological similarity to the first
      lesion but represented a highly pleomorphic and mainly sarcomatoid differentiated
      malignant tumor. The lack of expression of GFAP or MAP-2 raised the question of a
      secondary malignancy, however, molecular genetic analysis of IDH1 and p53
      revealed the same mutations in the anaplastic astrocytoma from 2006 as in the
      sarcomatoid tumor operated in 2010. Furthermore, accumulation of mutated IDH1 and
      TP53 protein could be demonstrated immunohistochemically. Thus, the second tumor
      represented the rare instance of recurrence of an anaplastic astrocytoma as a
      secondary gliosarcoma and a second malignant neoplasm was ruled out. The
      postoperative therapy and the inflammation might have contributed to the severe
      change in morphological phenotype of the glioma.

PMID- 21955927
TI  - Distinctive multicystic hemispheric lesions suggesting a novel variant of
      infantile astrocytoma.
AB  - Two unrelated female infants presented at 9 days and 2 months, respectively, with
      apneic episodes in the former and gaze preference in the latter. MRI revealed
      enlargement of almost the entire right hemisphere, apparently smooth cortex,
      simplification of the gyral pattern, and expanded white matter with abnormal
      signal intensity containing multiple intraparenchymal cysts. Histologic
      examination of both cases revealed white matter infiltration by a hypocellular
      lesion composed of uniform, fibrillary astrocytes in a microcystic background.
      Multilocular tumor cysts were prominent, but Rosenthal fibers and eosinophilic
      granular bodies were absent. Very rare mitoses were seen in the absence of
      necrosis or vascular change. There was no convincing cortical infiltration, but
      the subpial zone was diffusely expanded by a band of astrocytes set in a dense
      fibrillar feltwork which opened out into numerous cystic spaces. No desmoplastic
      changes or associated atypical ganglion cells were identified. There was no
      evidence for a BRAFKIAA1549 fusion or BRAF mutation in one case tested. In
      conclusion, both lesions are not desmoplastic infantile
      astrocytoma/ganglioglioma, fibrillary astrocytoma, or typical for pilocytic
      astrocytoma. Such extreme subpial spread with cysts is most unusual and may
      suggest a novel variant of infantile astrocytoma.

PMID- 21955928
TI  - PET response and tumor stabilization under erlotinib and bevacizumab treatment of
      an intracranial lesion non-invasively diagnosed as likely chordoma.
AB  - INTRODUCTION: Chordoma is a rare and a slow-growing tumor originating from the
      notochord and commonly localized in the skull base. Surgery and occasionally
      radiotherapy have emerged as the treatments of choice. In the relapsed situations
      available treatment options are strictly limited; however, recently molecularly
      targeted agents have been proposed to be of potential beneficial value. THE CASE:
      A 63-year-old male presenting with seizures and an extradural mass in the left
      brain hemisphere. An attempt to resect the tumor was followed by severe
      bradycardia when manipulating with the dura and therefore discontinued. It was
      considered too hazardous even to take a biopsy specimen. The tumor was considered
      radiologically and macroscopically as a chordoma. As the tumor progressed after
      radiotherapy, chemotherapy with erlotinib in combination with cetuximab was
      initiated. This treatment was interrupted due to progressive disease and
      toxicity. However, combination treatment with erlotinib and bevacizumab
      normalized the uptake of [11C]methionine PET signal and resulted in a slight
      tumor shrinkage on MRI. The patient is still (March 2011) free of symptoms,
      without cranial nerve deficits or seizures. DISCUSSION: This report shows that
      erlotinib and bevacizumab in combination may completely quench the transport of
      the essential amino acid methionine to a treatment refractory intracranial tumor
      bearing radiological and clinical characteristics of a chordoma. Further studies
      are necessary to establish this strategy as a treatment option for this
      indication.

PMID- 21955930
TI  - Randomized controlled trial of mailed Nicotine Replacement Therapy to Canadian
      smokers: study protocol.
AB  - BACKGROUND: Considerable public health efforts are ongoing Canada-wide to reduce
      the prevalence of smoking in the general population. From 1985 to 2005, smoking
      rates among adults decreased from 35% to 19%, however, since that time, the
      prevalence has plateaued at around 18-19%. To continue to reduce the number of
      smokers at the population level, one option has been to translate interventions
      that have demonstrated clinical efficacy into population level initiatives.
      Nicotine Replacement Therapy (NRT) has a considerable clinical research base
      demonstrating its efficacy and safety and thus public health initiatives in
      Canada and other countries are distributing NRT widely through the mail. However,
      one important question remains unanswered--do smoking cessation programs that
      involve mailed distribution of free NRT work? To answer this question, a
      randomized controlled trial is required. METHODS/DESIGN: A single blinded, panel
      survey design with random assignment to an experimental and a control condition
      will be used in this study. A two-stage recruitment process will be employed, in
      the context of a general population survey with two follow-ups (8 weeks and 6
      months). Random digit dialing of Canadian home telephone numbers will identify
      households with adult smokers (aged 18+ years) who are willing to take part in a
      smoking study that involves three interviews, with saliva collection for 3
      HC/cotinine ratio measurement at baseline and saliva cotinine verification at 8
      week and 6-month follow-ups (N = 3,000). Eligible subjects interested in free NRT
      will be determined at baseline (N = 1,000) and subsequently randomized into
      experimental and control conditions to receive versus not receive nicotine
      patches. The primary hypothesis is that subjects who receive nicotine patches
      will display significantly higher quit rates (as assessed by 30 day point
      prevalence of abstinence from tobacco) at 6-month follow-up as compared to
      subjects who do not receive nicotine patches at baseline. DISCUSSION: The
      findings from the proposed trial are timely and highly relevant as mailed
      distribution of NRT require considerable resources and there are limited public
      health dollars available to combat this substantial health concern. In addition,
      findings from this randomized controlled trial will inform the development of
      models to engage smokers to quit, incorporating proactive recruitment and the
      offer of evidence based treatment. TRIAL REGISTRATION: ClinicalTrials.gov:
      NCT01429129.

PMID- 21955929
TI  - A physical map of Brassica oleracea shows complexity of chromosomal changes
      following recursive paleopolyploidizations.
AB  - BACKGROUND: Evolution of the Brassica species has been recursively affected by
      polyploidy events, and comparison to their relative, Arabidopsis thaliana,
      provides means to explore their genomic complexity. RESULTS: A genome-wide
      physical map of a rapid-cycling strain of B. oleracea was constructed by
      integrating high-information-content fingerprinting (HICF) of Bacterial
      Artificial Chromosome (BAC) clones with hybridization to sequence-tagged probes.
      Using 2907 contigs of two or more BACs, we performed several lines of comparative
      genomic analysis. Interspecific DNA synteny is much better preserved in
      euchromatin than heterochromatin, showing the qualitative difference in evolution
      of these respective genomic domains. About 67% of contigs can be aligned to the
      Arabidopsis genome, with 96.5% corresponding to euchromatic regions, and 3.5%
      (shown to contain repetitive sequences) to pericentromeric regions. Overgo probe
      hybridization data showed that contigs aligned to Arabidopsis euchromatin contain
      ~80% of low-copy-number genes, while genes with high copy number are much more
      frequently associated with pericentromeric regions. We identified 39
      interchromosomal breakpoints during the diversification of B. oleracea and
      Arabidopsis thaliana, a relatively high level of genomic change since their
      divergence. Comparison of the B. oleracea physical map with Arabidopsis and other
      available eudicot genomes showed appreciable 'shadowing' produced by more ancient
      polyploidies, resulting in a web of relatedness among contigs which increased
      genomic complexity. CONCLUSIONS: A high-resolution genetically-anchored physical
      map sheds light on Brassica genome organization and advances positional cloning
      of specific genes, and may help to validate genome sequence assembly and
      alignment to chromosomes.All the physical mapping data is freely shared at a
      WebFPC site (http://lulu.pgml.uga.edu/fpc/WebAGCoL/brassica/WebFPC/; Temporarily
      password-protected: account: pgml; password: 123qwe123.

PMID- 21955931
TI  - Risk taking and the adolescent reward system: a potential common link to
      substance abuse.
AB  - OBJECTIVE: Increased risk-taking behavior has been associated with addiction, a
      disorder also linked to abnormalities in reward processing. Specifically, an
      attenuated response of reward-related areas (e.g., the ventral striatum) to
      nondrug reward cues has been reported in addiction. One unanswered question is
      whether risk-taking preference is associated with striatal reward processing in
      the absence of substance abuse. METHOD: Functional and structural MRI was
      performed in 266 healthy young adolescents and in 31 adolescents reporting
      potentially problematic substance use. Activation during reward anticipation
      (using the monetary incentive delay task) and to gray matter density were
      measured. Risk-taking bias was assessed by the Cambridge Gamble Task. RESULTS:
      With increasing risk-taking bias, the ventral striatum showed decreased
      activation bilaterally during reward anticipation. Voxel-based morphometry showed
      that greater risk-taking bias was also associated with and partially mediated by
      lower gray matter density in the same structure. The decreased activation was
      also observed when participants with virtually any substance use were excluded.
      The group with potentially problematic substance use showed greater risk taking
      as well as lower striatal activation relative to matched comparison subjects from
      the main sample. CONCLUSIONS: Risk taking and functional and structural
      properties of the reward system in adolescents are strongly linked prior to a
      possible onset of substance abuse, emphasizing their potential role in the
      predisposition to drug abuse.

PMID- 21955932
TI  - Risk of death from accidental overdose associated with psychiatric and substance
      use disorders.
AB  - OBJECTIVE: Despite dramatic increases in the rate of fatal accidental overdose in
      recent years, risk factors for this outcome remain poorly understood,
      particularly in clinical populations. The authors examined the association of
      psychiatric and substance use diagnoses with death from accidental overdose.
      METHOD: The study followed a cohort of patients from 2000 to 2006. The cohort
      included all patients treated in Veterans Health Administration facilities during
      fiscal year 1999 who were alive at the start of fiscal year 2000 (N=3,291,891).
      Death by accidental overdose was determined using National Death Index records
      and defined as a death with underlying cause of death coded to ICD-10 codes X40
      X45 (N=4,485). Diagnoses were determined by patient medical records. RESULTS:
      Adjusting for demographic and clinical characteristics, hazard ratios of death by
      accidental overdose associated with prior psychiatric and substance use disorder
      diagnoses ranged from 1.8 to 8.8. Significant associations of non-substance
      related psychiatric disorders with risk of death by accidental overdose persisted
      after additional adjustment for substance use disorders (hazard ratios from 1.2
      to 1.8). Depressive disorders and anxiety disorders other than posttraumatic
      stress disorder had stronger associations with risk of medication-related
      overdose death (hazard ratios, 3.02 and 3.07, respectively) than with risk of
      overdose death related to alcohol or illegal drugs (hazard ratios, 1.89 and 1.23,
      respectively). CONCLUSIONS: Among patients receiving care from the Veterans
      Health Administration, death from accidental overdose was found to be associated
      with psychiatric and substance use disorders. The study findings suggest the
      importance of risk assessment and overdose prevention for vulnerable clinical
      subpopulations.

PMID- 21955933
TI  - The neural circuits that generate tics in Tourette's syndrome.
AB  - OBJECTIVE: The purpose of this study was to examine neural activity and
      connectivity within cortico-striato-thalamo-cortical circuits and to reveal
      circuit-based neural mechanisms that govern tic generation in Tourette's
      syndrome. METHOD: Functional magnetic resonance imaging data were acquired from
      13 individuals with Tourette's syndrome and 21 healthy comparison subjects during
      spontaneous or simulated tics. Independent component analysis with hierarchical
      partner matching was used to isolate neural activity within functionally distinct
      regions of cortico-striato-thalamo-cortical circuits. Granger causality was used
      to investigate causal interactions among these regions. RESULTS: The Tourette's
      syndrome group exhibited stronger neural activity and interregional causality
      than healthy comparison subjects throughout all portions of the motor pathway,
      including the sensorimotor cortex, putamen, pallidum, and substantia nigra.
      Activity in these areas correlated positively with the severity of tic symptoms.
      Activity within the Tourette's syndrome group was stronger during spontaneous
      tics than during voluntary tics in the somatosensory and posterior parietal
      cortices, putamen, and amygdala/hippocampus complex, suggesting that activity in
      these regions may represent features of the premonitory urges that generate
      spontaneous tic behaviors. In contrast, activity was weaker in the Tourette's
      syndrome group than in the healthy comparison group within portions of cortico
      striato-thalamo-cortical circuits that exert top-down control over motor pathways
      (the caudate and anterior cingulate cortex), and progressively less activity in
      these regions accompanied more severe tic symptoms, suggesting that faulty
      activity in these circuits may result in their failure to control tic behaviors
      or the premonitory urges that generate them. CONCLUSIONS: Our findings, taken
      together, suggest that tics are caused by the combined effects of excessive
      activity in motor pathways and reduced activation in control portions of cortico
      striato-thalamo-cortical circuits.

PMID- 21955935
TI  - Childhood trauma and psychosis: a case-control and case-sibling comparison across
      different levels of genetic liability, psychopathology, and type of trauma.
AB  - OBJECTIVE: The associations of two types of childhood trauma (abuse and neglect)
      with psychosis symptom domains were investigated in subjects with psychotic
      illness, high psychosis vulnerability, and average psychosis vulnerability.
      METHOD: Childhood trauma was assessed with the Childhood Trauma Questionnaire.
      Symptoms were assessed with the Positive and Negative Syndrome Scale in the
      patients (N=272) and with the Structured Interview for Schizotypy-Revised in the
      patients' siblings (N=258), and healthy comparison subjects (N=227). RESULTS:
      Childhood trauma was associated with psychotic disorder in a dose-response
      fashion in the comparison of patients and healthy subjects (adjusted odds
      ratio=4.53, 95% CI=2.79-7.35). The comparison of siblings and healthy subjects
      suggested that siblings shared a degree of trauma with the patients (adjusted
      odds ratio=1.61, 95% CI=0.95-2.61), but the patient-sibling comparison indicated
      much greater exposure in patients than in siblings (adjusted odds ratio=2.60, 95%
      CI=1.78-3.78). Childhood abuse but not neglect was associated with positive but
      not negative symptoms in a dose-response fashion in all three groups. There was
      no evidence for moderation by sex. CONCLUSIONS: Discordance in psychotic illness
      across related individuals can be traced to differential exposure to trauma. The
      association between trauma and psychosis is apparent across different levels of
      illness and vulnerability to psychotic disorder, suggesting true association
      rather than reporting bias, reverse causality, or passive gene-environment
      correlation. Positive psychotic symptoms in vulnerable individuals may arise as a
      consequence of the level and frequency of exposure to abuse rather than neglect,
      suggesting symptom-specific and exposure-specific underlying mechanisms.

PMID- 21955936
TI  - The value of atorvastatin over the product life cycle in the United States.
AB  - BACKGROUND: US health care reform mandates the reduction of wasteful health care
      spending while maintaining quality of care. Introducing new drugs into crowded
      therapeutic classes may be viewed as offering "me-too" (new drugs with a similar
      mechanism of action compared to existing drugs) drugs without incremental
      benefit. This article presents an analysis of the incremental costs and benefits
      of atorvastatin, a lipid-lowering agent. OBJECTIVE: This analysis models the cost
      effectiveness of atorvastatin over the product life cycle. METHODS: The yearly
      cost-effectiveness of atorvastatin compared to simvastatin was modeled from 1997
      to 2030 from the point of view of a US third-party payer. Estimates for
      incremental costs (in US $) and effects (in quality-adjusted life-years [QALYs])
      for the primary and secondary prevention of cardiovascular events were taken from
      previously published literature and adjusted for changes in drug prices over
      time. Estimates of total statin use were derived using the National Health and
      Nutrition Examination Survey. Sensitivity analyses were conducted to examine
      variations in study parameters, including drug prices, indications, and discount
      rates. RESULTS: Assuming increasing statin use over time (with a mean of 1.07
      million new users per year) and a 3% discount rate, the cumulative incremental
      cost-effectiveness ratio (ICER) of atorvastatin versus simvastatin ranged from
      cost-savings at release to a maximum of $45,066/QALY after 6 years of generic
      simvastatin use in 2012. Over the full modeled life cycle (1997-2030), the
      cumulative ICER of atorvastatin was $20,331/QALY. The incremental value of
      atorvastatin to US payers (after subtracting costs) was estimated at $44.57 to
      $194.78 billion, depending on willingness to pay. Findings from the sensitivity
      analyses were similar. A hypothetical situation in which atorvastatin did not
      exist was associated with a reduction in total expenditures but also a loss of
      QALYs gained. CONCLUSION: The cumulative ICER of atorvastatin varied across the
      product life cycle, increasing during the period between generic simvastatin
      entry and generic atorvastatin entry, and decreasing thereafter.

PMID- 21955937
TI  - Efficacy and tolerability of a new extended-release formulation of nicotinic acid
      in Korean adults with mixed dyslipidemia: an 8-week, multicenter, prospective,
      randomized, double-blind, and placebo-controlled trial.
AB  - BACKGROUND: Nicotinic acid is an effective treatment for dyslipidemia. Patients
      are more tolerant of the extended-release form of nicotinic acid because it has a
      lower incidence of side effects, such as facial flushing, than the immediate
      release formulation. OBJECTIVE: This study was designed to evaluate the efficacy
      and tolerability of an experimental extended-release formulation of nicotinic
      acid in Korean adults with mixed dyslipidemia as a regulatory requirement to
      allow marketing of this product in Korea. METHODS: This study was a multicenter,
      prospective, randomized, double-blind, and placebo-controlled trial. Patients
      with low high-density lipoprotein cholesterol (HDL-C) levels, high low-density
      lipoprotein cholesterol (LDL-C) levels, or high triglyceride levels were
      enrolled. Patients in the treatment group received 500 mg of extended-release
      niacin for 4 weeks and 1000 mg of extended-release niacin for the next 4 weeks.
      RESULTS: Twenty-five patients (24% males; mean [SD] age, 57.4 [6.9] years)
      comprised the treatment group, and 22 patients (5% males; mean [SD] age 61.8
      [8.3] years) comprised the placebo group. After 8 weeks of treatment, HDL-C
      levels were increased significantly in the treatment group (17.6% vs -1.7%,
      respectively, from 35 [7] mg/dL to 42 [11] mg/dL in the treatment group and from
      38 [6] mg/dL to 36 [7] mg/dL in the placebo group; P < 0.001). LDL-C levels were
      decreased significantly in the treatment group (-11.4% vs 3.6%, respectively,
      from 147 [33] mg/dL to 126 [22] mg/dL in the treatment group and from 146 [31]
      mg/dL to 148 [26] mg/dL in the placebo group; P = 0.003). The incidence of drug
      related adverse events, including facial flushing in the treatment group, was not
      significantly different from that in the placebo group. CONCLUSIONS: The tested
      extended-release formulation of nicotinic acid increased HDL-C levels
      significantly but decreased LDL-C levels with a low incidence of facial flushing
      in this small, select group of Korean adults with mixed dyslipidemia.

PMID- 21955939
TI  - Discovery of pyrazoles as novel FPR1 antagonists.
AB  - A series of pyrazole inhibitors of the human FPR1 receptor have been identified
      from high throughput screening. The compounds demonstrate potent inhibition in
      human neutrophils and attractive physicochemical and in vitro DMPK profiles to be
      of further interest.

PMID- 21955938
TI  - Identification and pathogenicity of a natural reassortant between a very virulent
      serotype 1 infectious bursal disease virus (IBDV) and a serotype 2 IBDV.
AB  - Infectious bursal disease virus (IBDV) causes an economically important,
      immunosuppressive disease in chickens. There are two serotypes of the virus that
      contain a bi-segmented double-stranded RNA genome. In December 2008, the first
      very virulent (vv)IBDV was identified in California, USA and in 2009 we isolated
      reassortant viruses in two different locations. Genome segment A of these
      reassortants was typical of vvIBDV serotype 1 but genome segment B was most
      similar to IBDV serotype 2. The CA-K785 reassortant caused 20% mortality in
      chickens but no morbidity or mortality in commercial turkey poults despite being
      infectious. There have been previous reports of natural reassortants between
      vvIBDV and other serotype 1 strains, but a natural reassortant between IBDV
      serotypes 1 and 2 has not been described. The apparent reassorting of California
      vvIBDV with an endemic serotype 2 virus indicates a common host and suggests
      vvIBDV may have entered California earlier than originally thought.

PMID- 21955940
TI  - Secoiridoid glucosides and related compounds from Syringa reticulata and their
      antioxidant activities.
AB  - A 70% EtOH extract from the bark of Syringareticulata has shown significant
      antioxidant activity. Chemical study on the extract resulted in the isolation of
      seventeen compounds (1-17), including a novel oleoside-type secoiridoid
      glucoside, reticuloside (1), and the structures were elucidated on the basis of
      extensive spectroscopic analyses. Among the isolated compounds, jaspolyoside (2),
      oleuropein (4) and 2-(3,4-dihydroxy)-phenylethyl-beta-d-glucopyranoside (17),
      showed the most potent superoxide anion scavenging activity with the EC(50)
      values of 4.97, 2.57 and 4.97MUM, respectively. The structure-activity
      relationship indicated that the presence of 2-(3,4-dihydroxyphenyl)-ethoxy group
      is important for exhibiting the activity.

PMID- 21955941
TI  - Synthesis of lipids for development of multifunctional lipid-based drug-carriers.
AB  - A simple approach to synthesize phospholipids to modulate drug release and track
      lipid-based particulate drug-carriers is described. We synthesized two ether
      lipids, 1 1-O-hexadecyl-2-pentadenoyl-sn-glycerol-3-phosphocholine (C(31)PC) and
      2 1-O-hexadecyl-2-pentadenoyl-sn-glycerol-3-phosphomethanol (C(31)PM), and
      examined their ability to alter enzymatically triggered release of 6
      carboxyfluorescein from liposomes incubated in TRIS buffer or fetal bovine serum
      solutions. Further, we demonstrated that odd-chain lipids, for example, C(31)PC,
      could be identified in rat plasma without interference of endogenous lipids. This
      approach can be adapted to synthesize a variety of lipids for use in developing
      and optimizing multifunctional drug-carriers.

PMID- 21955942
TI  - Utilizing G-quadruplex formation to target 8-oxoguanine in telomeric sequences.
AB  - Utilizing G-quadruplex specific ligands that can induce/bind G-quadruplex DNA in
      human telomeric regions has recently become an attractive means for cancer
      chemotherapy because the formation of G-quadruplex structures inhibits the
      activity of telomerase, a reverse transcriptase mainly expressed in cancer cells.
      In the present work, we synthesized a type of bifunctional molecules that
      selectively bind to telomeric DNA via G-quadruplex formation and subsequently
      react with proximate OxodG in the presence of one-electron oxidant. Such
      molecules could be useful for telomerase inhibition. Perylene derivatives (7 and
      9) containing 1,3-diamino moieties were prepared for demonstration. The binding
      of 7 with G-quadruplex DNA was determined using UV thermal denaturation and the
      corresponding binding constant was derived from UV titration. The interactions of
      7 with G-quadruplex DNA containing OxodG were characterized using circular
      dichroism. Gel electrophoresis revealed that 7 can form more adducts with OxodG
      in G-quadruplex regions than that in duplex DNA.

PMID- 21955943
TI  - Investigation of the pyrazinones as PDE5 inhibitors: evaluation of regioisomeric
      projections into the solvent region.
AB  - We describe the design, synthesis and profiling of a novel series of PDE5
      inhibitors. We take advantage of an alternate projection into the solvent region
      to identify compounds with excellent potency, selectivity and pharmacokinetic
      profiles.

PMID- 21955944
TI  - Discovery of a series of potent and selective human H4 antagonists using ligand
      efficiency and libraries to explore structure-activity relationship (SAR).
AB  - We describe the identification of a potent, selective lead series that shows
      antagonism against the human histamine H4 receptor from thirteen actives
      identified in an HTS as part of a hit to lead program. By focusing on ligand
      efficiency and concurrently using a diversity based approach, compounds based
      around 2,4-diaminopyrimidine were identified with compound 25 being quickly shown
      to be a good lead. It also had the highest ligand efficiency in the series.

PMID- 21955945
TI  - The successful quest for oral factor Xa inhibitors; learnings for all of
      medicinal chemistry?
AB  - The medicinal chemistry of oral small molecule factor Xa inhibitors is discussed,
      highlighting key advances that led to clinical candidates and the first licensed
      medicines. Identification of neutral ligands for the primary specificity pocket
      was a key discovery; capitalised upon by structure based design and combinatorial
      methods to deliver many variations on the theme; but it was good medicinal
      chemistry practice, in the optimisation of physical properties, which ultimately
      delivered efficacious compounds with adequate oral exposure. As a retrospective
      appraisal, representative compounds were profiled using the more contemporary
      concepts of Ligand Efficiency and Property Forecast Indices; which gave clear
      indications of the value of these principles.

PMID- 21955946
TI  - Experimental (FT-IR, FT-Raman) and theoretical (HF and DFT) investigation and
      HOMO and LUMO analysis on the structure of p-fluoronitrobenzene.
AB  - FT-IR and FT-Raman spectra of p-fluoronitrobenzene (FNO(2)C(6)H(4)) have been
      recorded in the region 4000-100 cm(-1). In this work, the experimental and
      theoretical spectra of p-fluoronitrobenzene (p-FNBz) are studied. The molecular
      geometry and vibrational frequencies are calculated in the ground state of
      molecule using ab initio Hartree-Fock (HF) and DFT (B3LYP and LSDA) methods with
      6-31++G(d,p) and 6-311++G(d,p) basis sets. The computed values of frequencies are
      scaled to yield good coherence with observed values by using suitable factor. The
      complete assignments are performed on the basis of the total energy distribution
      (TED) of the vibrational modes, calculated with scaled quantum mechanics (SQM)
      method. The observed and calculated frequencies are found to be in very good
      agreement. The alteration of vibration bands due to the substitutions at the
      first and fourth position of the skeletal ring is also investigated from their
      characteristic region of linked spectrum. A study on the electronic properties,
      such as absorption wavelengths, excitation energy, dipole moment and frontier
      molecular orbital energies, are performed by time dependent DFT (TD-DFT)
      approach. The electronic structure and the assignment of the absorption bands in
      the electronic spectra of steady compounds are discussed. The calculated HOMO and
      LUMO energies show that charge transfer occurs within the molecule. The
      thermodynamic properties of the title compound at different temperatures have
      been calculated in gas phase, revealing the correlations between standard heat
      capacities (C) standard entropies (S), standard enthalpy changes (H) and
      temperatures.

PMID- 21955947
TI  - Effect of pH on the interaction of vitamin B12 with bovine serum albumin by
      spectroscopic approaches.
AB  - The interaction mechanism between vitamin B12 (B12, cyanocobalamin) and bovine
      serum albumin (BSA) has been investigated by fluorescence, synchronous
      fluorescence, ultraviolet-vis (UV) absorbance, and three-dimensional
      fluorescence. The intrinsic fluorescence of BSA was strongly quenched by the
      addition of B12 in different pH buffer solutions (pH 2.5, 3.5, 5.0, 7.4, and 9.0)
      and spectroscopic observations are mainly rationalized in terms of a static
      quenching process at lower concentration of B12 (C(B12)/C(BSA)<5) and a combined
      quenching process at higher concentration of B12 (C(B12)/C(BSA)>5). The
      structural characteristics of B12 and BSA were probed, and their binding
      affinities were determined under different pH conditions. The results indicated
      that the binding abilities of B12 to BSA in the acidic and basic pH regions (pH
      2.5, 3.5, 5.0, and 9.0) were lower than that at simulating physiological
      condition (pH 7.4). In addition, the efficiency of energy transfer from
      tryptophan fluorescence to B12 was found to depend on the binding distance r
      between the donor and acceptor calculated using Forster's theory. The effect of
      B12 on the conformation of BSA was analyzed using UV, synchronous fluorescence
      and three-dimensional fluorescence under different pH conditions. These results
      showed that the binding of B12 to BSA causes apparent change in the secondary and
      tertiary structures of BSA.

PMID- 21955948
TI  - Binding interaction of bioactive imidazole with bovine serum albumin--a
      mechanistic investigation.
AB  - A novel Y-shaped imidazole derivative 4-((E)-2-(4,5-diphenyl-1-p-tolyl-1H
      imidazol-2-yl)vinyl)phenol has been synthesized and characterised by IR, UV-vis,
      mass and NMR spectral techniques. The mutual interaction of this imidazole
      derivative (DPTIV) with bovine serum albumin (BSA) was investigated using
      photoluminescent studies. The fluorescence quenching mechanism of BSA by DPTIV
      was analyzed and the binding constant has been calculated. The binding distance
      between DPTIV and BSA was obtained based on the theory of Forester's non
      radiation energy transfer. The effect of some common ions on the binding constant
      between DPTIV and BSA was also examined.

PMID- 21955949
TI  - Polyborates in aqueous borate solution: a Raman and DFT theory investigation.
AB  - The geometries, energies and vibrational frequencies of various polyborates in
      both gaseous and aqueous phase were calculated at the B3LYP/aug-cc-pVDZ level.
      The calculated total symmetrical stretching Raman shifts of B(OH)(3), B(OH)(4)(
      ), B(2)O(OH)(4), B(2)O(OH)(5)(-), B(2)O(OH)(6)(2-), B(3)O(3)(OH)(3),
      B(3)O(3)(OH)(4)(-), B(3)O(3)(OH)(5)(2-), B(3)O(3)(OH)(6)(3-), B(4)O(5)(OH)(4)(2-)
      and B(5)O(6)(OH)(4)(-) were assigned to 877.40, 735.33, 785.22, 792.90, 696.79,
      587.72, 599.06, 740.16, 705.01, 551.67 and 521.04cm(-1), respectively. The
      results can be used as the characteristic frequency for polyborates in aqueous
      phase at room temperature. At least six types of polyborates B(OH)(3), B(OH)(4)(
      ), B(3)O(3)(OH)(4)(-), B(3)O(3)(OH)(5)(2-), B(4)O(5)(OH)(4)(2-) and
      B(5)O(6)(OH)(4)(-), occur in aqueous solutions at ambient temperature. The
      chemical species distribution and the relevant interaction mechanisms among
      polyborates in the solutions were also suggested.

PMID- 21955950
TI  - Optical properties and structural evaluation of Li2O-Al2O3-SiO2-TiO2 glassy
      semiconductor containing passive agent CeO2.
AB  - In the present work, the effect of CeO(2) as the passive agent on glassy
      structure of Li(2)O-Al(2)O(3)-SiO(2)-TiO(2) (LAST) material for production of a
      new amorphous semiconductor has been investigated. Optical properties and
      vibrational spectroscopy of the samples have been studied using UV-Vis and FTIR
      absorption spectra, respectively. Accordingly, structural variations of 0-1.5%
      CeO(2):LAST glasses were evaluated by calculation of density, molar volume,
      Urbach band tailing, direct and indirect optical band gaps, Fermi energy level
      and metallization criterion. Eventually for the analysis of the variation of
      energy level in presence of passive agent CeO(2), Licciardello's model for glassy
      semiconductors was utilized. Results of the investigation illustrates that while
      Ce(3+) ions could be regarded as the color agents due to spin allowed f-f
      transition, Ce(4+) ions might have a destructive influence on negative-U centers
      (color centers) of the glass and hence, reduce the recombination centers in the
      band gap of the glass.

PMID- 21955951
TI  - Prediction of therapeutic response to cervical epidural steroid injection
      according to distribution of radicular pain.
AB  - OBJECTIVE: This study aimed to determine whether the distribution of radicular
      pain has predictive value in identifying patients who would benefit from
      transforaminal cervical epidural steroid injections. DESIGN: Retrospective cohort
      study of subjects with cervical radiculopathy who underwent cervical epidural
      steroid injections from February 2005 to January 2006. Data from subjects were
      divided into groups based on pain distribution, imaging-based diagnosis of
      cervical disk herniation or stenosis, and their response to treatment. chi tests
      were used to assess the relationships between distribution and benefit. RESULTS:
      Of the 117 charts reviewed, complete data were available for 94 subjects. Forty
      eight subjects had cervical disk herniations and, of these, 52% had pain above
      the elbow with 60% benefit, and 48% had pain below the elbow with 61% benefit.
      Forty-six subjects had cervical stenosis and, of these, 57% had pain above the
      elbow with 62% benefit, and 43% had pain below the elbow with 80% benefit.
      Benefit was defined as 70% or greater reduction in pain. chi testing demonstrated
      no statistically significant difference in beneficial response to cervical
      epidural steroid injections based on pain distributions. CONCLUSIONS: The
      likelihood of subjects to report a positive benefit from cervical epidural
      steroid injections as a treatment of their cervical radicular pain was
      independent of the distribution of their pain. Although our results did not show
      pain distribution to have a predictive value, additional research is needed in
      identifying predictive factors to improve outcomes and reduce cost.

PMID- 21955952
TI  - Diagnosing Tapia syndrome using a videofluoroscopic swallowing study and
      electromyography after anterior cervical spine surgery.
AB  - A couple of the most common complications after anterior cervical spine surgery
      are dysphagia and hoarseness. This is often related to recurrent laryngeal nerve
      palsy and it can also be caused by injury to the branches of the lower cranial
      nerves. In general, Tapia syndrome is combined injuries of the recurrent
      laryngeal nerve of the vagus and the hypoglossal nerves. There has been no
      reported case until now of Tapia syndrome after a patient underwent anterior
      cervical spine surgery. We present here the case of a 42-yr-old man who
      complained of hoarseness, dysphagia, and right deviation of the tongue with an
      atrophic change for 2 mos after he underwent C3-4 discectomy and anterior fusion
      body. We found that he has a diagnosis of a variant of Tapia syndrome, although
      recurrent laryngeal nerve injury did not seem to be involved according to a
      videofluoroscopic swallowing study and electromyography. Our case report
      demonstrates that the combined diagnostic tools of videofluoroscopic swallowing
      study, electromyography, and laryngoscopy can be very useful in localizing and
      evaluating the level of lesions in patients with Tapia syndrome. 

PMID- 21955953
TI  - Spinal muscular atrophy type 1: avoidance of hospitalization by respiratory
      muscle support.
AB  - OBJECTIVE: The aim of this study was to report the outcomes of an oximetry
      protocol using up to continuous full ventilator-setting noninvasive ventilation
      (NIV) and mechanically assisted coughing (MAC) to avoid episodes of acute
      respiratory failure and hospitalizations for children with spinal muscular
      atrophy type 1 under 3 yrs of age. DESIGN: This study was a retrospective chart
      review of 16 patients with spinal muscular atrophy type 1 under 3 yrs of age
      consecutively referred for respiratory decompensations resulting in continuous
      NIV dependence and oxyhemoglobin desaturation. An avoided hospitalization was
      defined by the need for continuous NIV using high span bilevel positive airway
      pressure and reversal of desaturations by MAC in the home setting. The protocol
      included training and equipping parents to use NIV, MAC, and basic life support.
      RESULTS: There were 49 acute episodes (1.20/patient per year), of which 43 met
      the criteria for an avoided hospitalization. Therefore, only six episodes
      (0.15/patient per year) required hospitalization, and four required endotracheal
      intubation (0.1/patient per year). Three of the four were extubated after 4, 9,
      and 15 days, respectively, to full NIV support and aggressive MAC. The fourth
      patient, for whom NIV could not be provided, underwent an emergency intubation at
      home and died at the age of 40 mos. CONCLUSIONS: A protocol including high span
      bilevel positive airway pressure along with MAC to expel airway secretions and
      normalize oxyhemoglobin saturation can be used by trained caregivers to avoid
      episodes of acute respiratory failure and hospitalization for children with
      spinal muscular atrophy type 1 under 3 yrs of age.

PMID- 21955954
TI  - Influenza vaccination in patients with pulmonary sarcoidosis: efficacy and
      safety.
AB  - BACKGROUND: Sarcoidosis is an inflammatory, granulomatous disorder of unknown
      etiology. The role of cellular and humoral immune systems in this disease is
      unclear, whereas dysregulation of the immune system is suggested. Patients with
      sarcoidosis show diverse responses while exposed to various antigens. Although
      influenza vaccination is recommended in pulmonary sarcoidosis, its efficacy and
      safety has not been investigated. OBJECTIVES:   To evaluate safety and
      immunogenicity of influenza vaccine in patients with sarcoidosis.
      PATIENTS/METHODS: Influenza vaccination was performed in 23 eligible patients
      with sarcoidosis (SP) and 26 healthy controls (HC). Antibody titers against H1N1,
      H3N2, and B influenza virus antigens were evaluated just before and 1 month after
      vaccination. Patients were followed for 6 months to assess vaccine safety.
      RESULTS: Serological response and magnitude of changes in antibody titers against
      influenza vaccine antigens were comparable between SPs and HCs. Women showed a
      better serological response against B antigen (P = 0.034) than men. Twenty-four
      hour urine calcium was associated with antibody response against H1N1
      [correlation coefficient (CC) = 0.477, P = 0.003] and H3N2 (CC = 0.352, P =
      0.028) antigens. Serum angiotensin-converting enzyme correlated negatively with
      antibody response against B antigen (CC = -0.331, P = 0.040). Higher residual
      volume was associated with fewer rises in antibody titer against H3N2 antigen (CC
      = -0.377, P = 0.035). No major adverse events or disease flare-up was observed
      during follow-up. CONCLUSIONS: In this study, influenza vaccination did not cause
      any major adverse event in SPs, and their serological response was equal to HCs.
      Studies with larger sample size and a broader selection of subjects could help
      validate the results of this study.

PMID- 21955955
TI  - Challenges of genetic testing in adolescents with cardiac arrhythmia syndromes.
AB  - The ability to sequence individual genomes is leading to the identification of an
      increasing number of genetic risk factors for serious diseases. Knowledge of
      these risk factors can often provide significant medical and psychological
      benefit, but also raises complex ethical and social issues. This paper focuses on
      one area of rapid progress: the identification of mutations causing long QT
      syndrome and other cardiac channel disorders, which can explain some previously
      unexplained deaths in infants (SIDS) and children and adults (SUDS) and prevent
      others from occurring. This genetic knowledge, discovered posthumously in many
      cases, has implications for clinical care for surviving family members who might
      carry the same mutations. The information obtained from genetic testing, in the
      context of personal and family history, can guide individually tailored
      interventions that reduce risk and save lives. At the same time, obtaining and
      disclosing genetic information raises difficult issues about confidentiality and
      decision making within families. We draw on the experience of the Montefiore
      Einstein Center for Cardiogenetics, which has played a leading role in the
      genetic diagnosis and clinical management of cardiac channel diseases, to explore
      some of the challenging ethical questions arising in affected families with
      adolescent children. We focus on the related issues of (1) family
      confidentiality, privacy and disclosure and (2) adolescent decision making about
      genetic risk, and argue for the value of interdisciplinary dialogue with affected
      families in resolving these issues.

PMID- 21955956
TI  - 'Equivalence of care' in prison medicine: is equivalence of process the right
      measure of equity?
AB  - In recent years, the principle of equivalence has been accepted in many countries
      as the standard against which healthcare provision for prisoners should be
      measured. There are several ways in which this principle can be interpreted, but
      current policy in the UK and elsewhere seems to focus on the measurement and
      achievement of equivalence in the process of healthcare provision. We argue that
      it is not appropriate to apply this interpretation to all aspects of prisoner
      healthcare, as it does not necessarily address the challenges inherent to the
      prisoner population and prison setting. Consequently equivalence of health
      outcomes should also be considered alongside processes in the interests of
      providing healthcare in prison that is equivalent to that outside prison.

PMID- 21955957
TI  - Senior doctors' opinions of rational suicide.
AB  - CONTEXT: The attitudes of medical professionals towards physician assisted dying
      have been widely discussed. Less explored is the level of agreement among
      physicians on the possibility of 'rational suicide'-a considered suicide act made
      by a sound mind and a precondition of assisted dying legislation. OBJECTIVE: To
      assess attitudes towards rational suicide in a representative sample of senior
      doctors in England and Wales. METHODS: A postal survey was conducted of 1000
      consultants and general practitioners randomly selected from a commercially
      available database. The main outcome of interest was level of agreement with a
      statement about rational suicide. RESULTS: The corrected participation rate was
      50%; 363 questionnaires were analysed. Overall 72% of doctors agreed with the
      possibility of rational suicide, 17% disagreed, and 11% were neutral. Doctors who
      identified themselves as being more religious were more likely to disagree. Some
      doctors who disagreed with legalisation of physician assisted suicide
      nevertheless agreed with the concept of rational suicide. CONCLUSIONS: Most
      senior doctors in England and Wales feel that rational suicide is possible. There
      was no association with specialty. Strong religious belief was associated with
      disagreement, although levels of agreement were still high in people reporting
      the strongest religious belief. Most doctors who were opposed to physician
      assisted suicide believed that rational suicide was possible, suggesting that
      some medical opposition is best explained by other factors such as concerns of
      assessment and protection of vulnerable patients.

PMID- 21955958
TI  - Postprandial metabolic responses to mixed versus liquid meal tests in healthy men
      and men with type 2 diabetes.
AB  - AIMS: Compare metabolic responses after mixed versus liquid meals of similar
      caloric/nutritional content in healthy and type 2 diabetes (T2D) subjects.
      METHODS: Ten healthy men and 10 men with T2D received mixed and liquid meals
      after an overnight fast. Classical (insulinogenic index; insulin/glucose areas
      under curves, AUC(insulin)/AUC(glucose)) and model-based (beta-cell glucose
      sensitivity; rate sensitivity; potentiation factor ratio, PFR) beta-cell function
      estimates were calculated. Between-meal differences in glucose, insulin, C
      peptide, triglyceride (TG), beta-cell function and oral glucose insulin
      sensitivity (OGIS) and between-meal correlations for beta-cell function and OGIS
      were evaluated. RESULTS: Among healthy subjects, beta-cell function and OGIS were
      similar between meals. C-peptide (p=0.03), insulin (p=0.002),
      AUC(insulin)/AUC(glucose) (p=0.004) and insulin secretion (p=0.04) were higher
      after the liquid meal. Among T2D subjects, glucose, insulin, C-peptide, beta-cell
      function, and OGIS were similar. PFR was higher (p=0.004) and TG increased more
      slowly (p=0.002) after the liquid meal. OGIS and beta-cell function were
      correlated during both meals in both groups (r=0.66-0.98), except incremental
      AUC(insulin)/AUC(glucose), rate sensitivity, and, in healthy subjects, PFR.
      CONCLUSIONS: Metabolic responses after mixed or liquid meals of similar content
      were highly correlated in T2D and healthy subjects. In T2D, the liquid meal
      produced beta-cell function estimates generally similar to the mixed meal.

PMID- 21955959
TI  - Point-of-care beta-hydroxybutyrate testing for assessing diabetic ketoacidosis
      severity prior to treatment in the emergency department.
AB  - We prospectively evaluated the correlation between point-of-care beta-OHB values
      and DKA severity at time of initial diagnosis in 54 patients. The correlation
      coefficients between beta-OHB and pH, bicarbonate and anion gap were 0.33, 0.25
      and 0.16, respectively. We conclude that point-of-care beta-OHB absolute values
      cannot reliably assess DKA severity.

PMID- 21955960
TI  - Reclassification of diabetes type in pediatric patients initially classified as
      type 2 diabetes mellitus: 15 years follow-up using routine data from the
      German/Austrian DPV database.
AB  - OBJECTIVE: To examine change of diagnosis in patients from the German/Austrian
      multicenter DPV (Diabetes Patienten Verlaufsdokumentation) database initially
      classified as type 2 diabetes. METHODS: Patients aged <=20 years at onset,
      diagnosed between 1995 and 2010 were followed for at least 6 months. Chi
      square/Wilcoxon tests were performed to compare patient groups according to
      diabetes type after reclassification. RESULTS: From 580 study patients, 60
      (10.3%) were reclassified, on average 2.4 years after initial diagnosis as
      follows: 23 (38.3%) as type 1 diabetes; 9 (15%) as maturity onset diabetes of the
      young (MODY); 20 (33.3%) as "other specific diabetes forms" and 8 (13.3%) as
      "remission" of type 2 diabetes. Patients reclassified to type 1 were
      significantly younger (13.5 +/- 2.9 versus 14.0 +/- 2.6; p=0.027) and more often
      beta-cell antibody positive at disease onset (80.0% versus 31.2%; p=0.002), while
      patients reclassified as MODY had significantly lower BMI-SDS values than 520
      patients with confirmed type 2 diabetes (2.5 +/- 1.1 versus 0.9 +/- 1.1;
      p<0.001). The latter were also considerably more obese than patients in
      "remission" and those reclassified to "other specific diabetes forms".
      CONCLUSION: About 10% of patients in the DPV database, initially diagnosed as
      type 2 diabetes, were retrospectively reclassified.

PMID- 21955961
TI  - Impact of perioperative glycaemia and glycated haemoglobin on the outcomes of the
      surgical treatment of diabetic foot osteomyelitis.
AB  - Perioperative glycaemic control during admission was a predictive factor of
      amputation in a prospective cohort of 81 patients with diabetes who underwent
      surgical treatment for osteomyelitis. Glycaemic control before admission, as
      determined by glycosylated haemoglobin, did not have any influence on the
      outcomes.

PMID- 21955962
TI  - Changes in dietary habits and their association with metabolic markers after a
      non-intensive, community-based lifestyle intervention to prevent type 2 diabetes,
      in Greece. The DEPLAN study.
AB  - AIMS: The aim of the present study was to evaluate the impact on dietary and
      activity habits of a non-intensive, community based lifestyle intervention for
      type 2 diabetes prevention, in high-risk Greek individuals. METHODS: A total of
      191 high-risk persons were invited to participate in a one-year lifestyle
      intervention program, consisting of six bi-monthly sessions with a dietician. The
      dietary aims of the intervention were: reduction of saturated fat, sugars and
      refined cereals intake and at least five servings of fruits and vegetables,
      daily. Demographic, dietary, anthropometric, medical and biochemical indices were
      recorded at baseline and at the end of the intervention. RESULTS: The
      intervention was completed by 126 participants. At study end, participants
      reported decreased whole fat dairies and processed meats consumption (p=0.018 and
      0.016, respectively), sugars (p=0.006) and refined cereals (p=0.045).
      Participants who improved their diet, decreased body weight (p=0.040), plasma
      triglycerides (p=0.020) and 2-h post-load plasma glucose (p=0.05) compared to
      those who had worsened their dietary habits. Total time spent daily on physical
      activity, remained unchanged throughout the intervention. CONCLUSIONS: The
      implementation of a group-based, non-intensive dietary counseling proved to be
      practical and feasible in "real-world" community settings and was accompanied by
      favorable dietary changes and health benefits.

PMID- 21955964
TI  - Recognized by the National Library of Medicine.

PMID- 21955963
TI  - Developmental lead exposure causes startle response deficits in zebrafish.
AB  - Lead (Pb(2+)) exposure continues to be an important concern for fish populations.
      Research is required to assess the long-term behavioral effects of low-level
      concentrations of Pb(2+) and the physiological mechanisms that control those
      behaviors. Newly fertilized zebrafish embryos (<2h post fertilization; hpf) were
      exposed to one of three concentrations of lead (as PbCl(2)): 0, 10, or 30 nM
      until 24 hpf. (1) Response to a mechanosensory stimulus: Individual larvae (168
      hpf) were tested for response to a directional, mechanical stimulus. The tap
      frequency was adjusted to either 1 or 4 taps/s. Startle response was recorded at
      1000 fps. Larvae responded in a concentration-dependent pattern for latency to
      reaction, maximum turn velocity, time to reach V(max) and escape time. With
      increasing exposure concentrations, a larger number of larvae failed to respond
      to even the initial tap and, for those that did respond, ceased responding
      earlier than control larvae. These differences were more pronounced at a
      frequency of 4 taps/s. (2) Response to a visual stimulus: Fish, exposed as
      embryos (2-24 hpf) to Pb(2+) (0-10 MUM) were tested as adults under low light
      conditions (~ 60 MUW/m(2)) for visual responses to a rotating black bar. Visual
      responses were significantly degraded at Pb(2+) concentrations of 30 nM. These
      data suggest that zebrafish are viable models for short- and long-term
      sensorimotor deficits induced by acute, low-level developmental Pb(2+) exposures.

PMID- 21955965
TI  - Clinical tolerance and toxicity of intravenous baclofen: a pilot study in a
      canine model.
AB  - OBJECTIVE: Assess safety and tolerance of intravenous (IV) baclofen using a dog
      model. DESIGN: Prospective pharmacokinetic study involving 6 adult dogs. Two dogs
      received baclofen 10 mg oral and IV bolus doses. Subsequent 4 dogs were given IV
      boluses of 0.5, 1.0 and 1.5 mg/kg followed by constant infusion of baclofen
      (rates of 0.1, 0.2 and 0.4 mg/kg/hour). Also, dogs were given single IV 2 and 3
      mg /kg bolus doses. Outcome measures included clinical observation scales and
      baclofen levels. RESULTS: Oral bioavailability was 0.66 and 0.69 in 2 dogs.
      Following IV baclofen, terminal phase half-lives were 3.3 and 3.6 hours. Single
      bolus doses of 2 and 3 mg/kg caused mild to moderate clinical changes which were
      delayed at least 2 hours after peak blood levels. Boluses of 0.5 and 1.0 mg/kg
      with constant infusion between boluses were tolerated, however within 30 minutes
      of beginning constant infusion of 0.2 mg/kg/hr after the second bolus (1.0
      mg/kg), dogs showed progressive sedation and ataxia. Clinical improvement
      occurred within 7 hours of stopping baclofen. Dogs appeared normal by the next
      morning. CONCLUSIONS: IV baclofen bolus doses of 0.5 to 3 mg/kg were well
      tolerated. Maximum clinical effect was delayed for at least 2 hours after peak
      plasma levels.

PMID- 21955966
TI  - Neonatal brachial plexus palsy - historical perspective.

PMID- 21955967
TI  - Functional assessments in the future of NBPP.

PMID- 21955968
TI  - Anatomy of the brachial plexus.
AB  - The brachial plexus is a complex anatomical network of nerves that mainly
      supplies the upper limb. A thorough understanding of the anatomy of this region
      provides the clinician with valuable clinical information that is crucial for
      evaluating and planning treatment for patients with obstetrical brachial plexus
      palsy. We will highlight the anatomy of the brachial plexus and relevant clinical
      correlation between physical findings and the anatomical location of the level of
      the injury.

PMID- 21955969
TI  - Neonatal brachial plexus injury: obstetrical factors and neonatal management.
AB  - Neonatal brachial plexus injury (BPI) is a birth outcome characterized by injury
      to the brachial plexus identified after delivery. Though uncommon, its potential
      occurrence following delivery is concerning for both the delivering clinician as
      well as the pediatric team. Considerable research looking at delivery factors,
      including forces applied at the time of delivery and management of the BPI after
      it has occurred, has led to a better understanding, if not a lower rate, of BPI.
      This information is reviewed below.

PMID- 21955970
TI  - Pathogenesis and management of deformities of the elbow, wrist, and hand in late
      neonatal brachial plexus palsy.
AB  - The incidence of neonatal brachial plexus palsy (NBPP) has remained relatively
      stable despite awareness of the problem and improved obstetric techniques.
      Deformities of the forearm and hand can result either from untreated NBPP or
      following early microsurgical nerve reconstruction. These deformities include
      limb length discrepancy, flexion contracture of the elbow, supination or
      pronation contractures of the forearm, ulnar deviation of the wrist, and varying
      types of finger paralysis. The treatment options for these deformities consist of
      soft tissue releases, corrective osteotomies, tendon transfers, joint fusions,
      and/or free muscle transfers. Rehabilitation and physical therapy treatment are
      critical after these procedures. This article reviews the pathogenesis of the
      common deformities seen in a late presentation of NBPP, the assessment of these
      children, and provides a reconstructive strategy for the management of this
      difficult problem.

PMID- 21955971
TI  - Shoulder sequelae of neonatal brachial plexus injuries: orthopedic assessment and
      management.
AB  - Brachial plexus birth palsy occurs at a rate of 1/1000-4/1000 live births despite
      advances in prenatal and obstetric care. The majority of children recover
      spontaneously, however some are left with permanent neurologic deficit. Shoulder
      pathology results from muscle imbalance created by pairing of weak or paralyzed
      muscles with unaffected muscle groups around the shoulder. This imbalance results
      in soft tissue contracture and can cause progressive glenohumeral joint
      morphological changes. Contractures of internal rotation are most common and may
      be a source of disability for the child. Treatment of the infant with brachial
      plexus palsy is initially centered around therapy and prevention of contracture.
      Surgical intervention can improve global shoulder function, and is reserved for
      patients who develop functionally limiting contractures, glenohumeral joint
      morphological changes, or findings of instability. A thorough physical
      examination, appropriate imaging, and assessment of the goals and expectations of
      the family are warranted prior to proceeding with any treatment course. The
      progressive and functionally limiting course of the shoulder sequelae in brachial
      plexus palsy emphasizes the need for early recognition and appropriate
      management. The purpose of this manuscript is to review orthopedic evaluation and
      management of neonatal brachial plexus palsy (NBPP) to promote early recognition
      and prompt referral.

PMID- 21955972
TI  - Nerve surgery for neonatal brachial plexus palsy.
AB  - Neonatal brachial plexus palsies may cause lifelong limitations to function of
      the upper limb. Early nerve reconstructive surgery may be indicated in selected
      cases. An overview is given of our current understanding of this type of nerve
      lesion in the developing child. The neuropathology of the injury is presented to
      provide a background for the understanding of its natural history, as well as for
      the rationale and methods for nerve surgical treatment. The assessment of upper
      limb function and the range of severity of the lesions at the very young age are
      outlined. Decision-making regarding surgical selection and determination of the
      appropriate procedures is presented, as are the outcomes. Improved function can
      be obtained with surgical repair.

PMID- 21955973
TI  - Fibrotendinous band causing neurogenic Thoracic Outlet Syndrome in adolescent
      with bilateral cervical ribs.
AB  - Thoracic Outlet Syndrome (TOS) describes a variety of symptoms caused by the
      compression of the neurovascular structures in the cervicoaxillary region as they
      leave the thorax toward the upper limbs. Causes of TOS are vascular and
      neurogenic, with neurogenic symptoms being the most common presentation (95% of
      patients). Symptoms related to neurogenic TOS include intrinsic hand muscle and
      thenar region atrophy and weakness, as well as medial hand and forearm numbness,
      which are all suggestive of lower trunk involvement. This condition is very rare
      in the pediatric population. We are reporting a case of true neurogenic TOS
      caused by a fibrotendinous band in an adolescent with bilateral cervical ribs who
      was submitted for surgical treatment at the right side.

PMID- 21955974
TI  - Nebulized tobramycin: prevention of pneumonias in patients with severe cerebral
      palsy.
AB  - BACKGROUND AND METHODS: In patients with severe cerebral palsy, pneumonias are a
      frequent occurrence and can lead to excessive morbidity and mortality. Similar
      poor outcomes can occur in patients with cystic fibrosis. Nebulized tobramycin
      has been shown to be effective in preventing pneumonias, and in improving lung
      function in cystic fibrosis patients. This study reports results from three
      patients with severe cerebral palsy who were suffering from recurrent pneumonias.
      We compared the 12 months prior to starting nebulized tobramycin, to the first 12
      months of intermittent therapy (28 days of nebulized antibiotic, followed by 28
      days with no antibiotic, then repeated). We noted the number of pneumonias, the
      number of hospitalizations due to pneumonia, and length of hospitalizations for
      pneumonia. RESULTS: Adding the results from the three patients together, the
      number of pneumonias went from 19 during the year prior to starting the nebulized
      tobramycin, to 11 during the year of treatment. The number of hospitalizations
      for pneumonia went from 11 to 0. The number of days in hospital for pneumonia
      went from 110 to 0. CONCLUSION: As in cystic fibrosis patients, patients with
      severe cerebral palsy may benefit from the intermittent use of nebulized
      tobramycin to prevent pneumonias and hospitalizations due to pneumonia. Further
      studies are warranted.

PMID- 21955976
TI  - Bilobular calcifying fibrous pseudotumor in soleus muscle: a case report.
AB  - INTRODUCTION: Calcifying fibrous pseudotumor is a rare benign soft-tissue lesion
      composed of fibrous tissue with abundant hyalinized collagen and dystrophic and
      often psammomatous calcifications. The cause of the disease is unclear but,
      usually, complete resection of the well-circumscribed tumor is sufficient to
      avoid recurrence of the disease. Here, we report an unusual case of this rare
      tumor that presented as two lobulated lesions in the calf muscle. CASE
      PRESENTATION: The patient was a 17-year-old Japanese girl who noted a hard mass
      in her left calf. Magnetic resonance imaging revealed two well-demarcated lobular
      masses in the soleus muscle, and the tumor was significantly enhanced by contrast
      medium. Preoperative differential diagnoses included soft-part tumors composed of
      fibrous tissue. However, making a definite diagnosis was impossible because a
      lobulated shape is rare for fibrous tumors. Biopsy demonstrated that the mass was
      a benign tumor composed of collagen-rich, hyalinized fibrosclerotic tissue. We
      performed marginal resection of the two nodules, including the fibrous tissue
      that connected them. Immunohistochemistry was positive for factor XIIIa and
      negative for anaplastic lymphoma kinase-1. These findings were helpful to
      distinguish calcifying fibrous pseudotumor from inflammatory myofibroblastic
      tumor. There was no sign of recurrence at 30 months after surgery. CONCLUSION: To
      the best of our knowledge, this is the first case of bilobular calcifying fibrous
      pseudotumor that developed in an extremity. As described in the previous
      literature, simple excision was sufficient for the treatment of calcifying
      fibrous pseudotumor with two lobules.

PMID- 21955977
TI  - Clinicopathological and prognostic significance of serum and tissue Dickkopf-1
      levels in human hepatocellular carcinoma.
AB  - BACKGROUND: Although Dickkopf-1 (DKK1) is known to be a negative regulator of the
      Wnt/beta-catenin pathway, it has been recently found to be upregulated in
      cancers. AIMS: We investigated the clinical and prognostic significance of both
      serum and transcript DKK1 and its functional roles in human hepatocellular
      carcinoma (HCC). METHODS: We evaluated the expression level of DKK1 in both
      tissue and serum samples from patients with HCC using GeneChip microarray and
      real-time-quantitative PCR and sandwich ELISA system respectively. The
      clinicopathological and prognostic significance of serum and tissue DKK1 levels
      was examined. Functional characterization of DKK1 with regard to cell migration,
      invasion and tumour growth was performed. RESULTS: Both DKK1 transcript and serum
      protein were upregulated in a stepwise manner in human HCCs. Its transcript
      levels were associated with more aggressive tumour behaviour, in terms of venous
      invasion (P = 0.003), advanced tumour stage (P = 0.003). DKK1 transcript
      correlated with shorter overall (P = 0.006) and disease-free survival (P =
      0.012), and higher serum DKK1 levels correlated with shorter disease-free
      survival (P = 0.046). Knockdown of DKK1 significantly reduced both migratory and
      invasive abilities of HCC cells, whereas overexpression of DKK1 enhanced the
      tumour formation efficiency and tumour growth in vivo. CONCLUSIONS: Serum and
      tissue DKK1 levels increased in a stepwise manner in multistep
      hepatocarcinogenesis and had prognostic significance. DKK1 plays a functional
      role in cell migration, invasion and tumour growth.

PMID- 21955978
TI  - Relationship of blood pressure to heart rate in isolated systolic hypertension.
AB  - BACKGROUND: Patients with isolated systolic hypertension (ISH) have been noted to
      be less responsive to beta-blockers than patients with essential hypertension
      (HTN). The purpose of this study was to determine the relationship between blood
      pressure (BP) and heart rate in ISH. METHODS: A total of 619 patients underwent
      24-hour ambulatory BP monitoring. Patients were grouped as normal, HTN, or ISH.
      Clinical characteristics, mean BPs, and mean heart rate were compared between the
      groups. RESULTS: Two hundred seventy-one patients had normal BP, 98 had HTN, and
      90 had ISH. Antihypertensives were used in 37% with normal BP, 51% with HTN, and
      58% with ISH. The pulse pressure was highest for ISH (67 [10] mm Hg), followed by
      HTN (59 [12] mm Hg) and normal BP (49 [7] mm Hg; P < 0.0001). Heart rate in ISH
      was 71 [10] beats per minute; slower than that for normal BP (73 [11] beats per
      minute; P = 0.0464) and HTN (78 [12] beats per minute; P < 0.0001).There was a
      positive relationship between diastolic BP and heart rate. In ISH, there was a
      negative relationship between systolic BP and heart rate (slope = -0.18; r =
      0.24; P = 0.0209) and a positive relationship between diastolic BP and heart rate
      (slope = 0.19; r = 0.33; P = 0.0015). CONCLUSIONS: The noted relationship of
      heart rate to systolic BP and pulse pressure may in part explain the lower
      efficacy of beta-blockers in patients with ISH. The rate-lowering effects of
      these medications may result in an increase in systolic and pulse pressures.

PMID- 21955979
TI  - Effect of infliximab treatment on QT intervals in patients with ankylosing
      spondylitis.
AB  - BACKGROUND: Cardiovascular complications are one of the most common and the most
      serious extraskeletal manifestations of ankylosing spondylitis (AS). Infliximab,
      a monoclonal antibody against tumor necrosis factor, is widely used in the
      treatment of AS. QT dispersion (QTd), which relates to left ventricular function
      and is used as an index of cardiac dysrhythmia, may be useful as a prognostic
      guide. Early detection of possible cardiac involvement may not be clinically
      evident, whereas it may be detected by electrocardiography. OBJECTIVES: The aim
      of this prospective study was to assess the effect of infliximab treatment on QT
      intervals in patients with AS. METHODS: Twenty-one patients (17 females and 4
      males) with AS who were in the active phase of disease (Bath Ankylosing
      Spondylitis Disease Activity Index score >4) were enrolled in the study.
      Infliximab was administered intravenously at a dosage of 5 mg/kg at weeks 0, 2,
      and 6 and every 6 weeks thereafter. QT intervals were recorded before and after 6
      months of treatment. RESULTS: QT corrected (QTc) for heart rate was significantly
      reduced in the patients with AS after 6 months of infliximab therapy (406 +/- 5.5
      vs 388 +/- 6.6 milliseconds; P = 0.029). There was no difference in the QTc
      dispersion (34.3 +/- 11.1 vs 34.1 +/- 8.6; P = 0.171). Body mass index and lipid
      profile were slightly increased after the treatment, but the difference was
      statistically insignificant. CONCLUSION: Inflammation can affect the ventricles
      with an unknown mechanism, and QTc may be slightly prolonged as a result in the
      active phase of AS. In our study, QTc was shortened under infliximab therapy by
      suppressing inflammation. Therefore, this effect may protect patients with AS
      from fatal arrhythmias and sudden cardiac death.

PMID- 21955980
TI  - Optimal management of older patients with chronic lymphocytic leukemia: some
      facts and principles guiding therapeutic choices.
AB  - Chronic lymphocytic leukemia (CLL) is a disease of older patients and median age
      at diagnosis is 72 years. This older group is under-represented in clinical
      trials, (median age 58-62 years). Here we review background data on incidence,
      survival, definitions of older age, fitness criteria, frailty and co-morbidities.
      Issues influencing the choice of therapy in older patients are also addressed and
      different therapeutic options are highlighted based on recent available data. Fit
      older patients with less co-morbidities benefit most from the very effective
      chemoimmunotherapy (FC-R) given for younger patients today, but whether other
      novel drug combinations or new agents are more suitable for less fit patients is
      still unsettled. Based on careful evaluation of published data from larger
      clinical trials and major referral centers we present our concept of therapy as a
      guide to optimal management for subgroups of older patients with CLL.

PMID- 21955981
TI  - Efficacy of trimming chilled beef during fabrication to control Escherichia coli
      O157:H7 surrogates on subsequent subprimals.
AB  - Effectiveness of trimming external carcass surfaces from subprimals during
      fabrication to reduce Escherichia coli O157:H7 surrogates was evaluated. Carcass
      sides (n = 10 sides) were inoculated along the hide pattern opening before
      entering the blast chill cooler with a gelatin slurry containing a bacterial
      cocktail of three rifampicin-resistant, nonpathogenic E. coli biotype I strains.
      Following a 48 h chill, sides were fabricated to produce eight subprimals.
      Microbiological samples were taken from the original carcass fat surface area,
      initial lean surface area, trimmed fat surface area (where applicable), and
      trimmed lean surface area (where applicable). Newly exposed lean surfaces had
      lower (P < 0.05) counts of rifampicin-resistant E. coli than did the external fat
      surfaces. However, fat and lean surfaces that were not inoculated became
      contaminated during the fabrication process. Trimming external surfaces reduced
      levels of pathogens, but under normal fabrication processes, pathogens were still
      spread to newly exposed surfaces.

PMID- 21955982
TI  - Sensory and texture properties of Italian typical dry-cured hams as related to
      maturation time and salt content.
AB  - Maturing time and salt were fixed factors and fat was a covariate in a full
      factorial design study of sensory and texture properties of 36 dry cured hams.
      Samples were chosen to fit three ageing and salt classes. Differences (P < 0.05)
      in sensory scores were found between whole slices (with cover fat) and their
      biceps femoris (BF) counterparts, with sweet taste enhanced in whole samples and
      conversely unpleasant bitter taste more intense in BF portions. Increased ageing
      time resulted in better sensory profiles, as documented by greater scores (P <
      0.05) for matured odour, matured taste and sweet taste, whereas salty taste was
      reduced. Decreased salt was associated with greater intensities (P < 0.05) of
      undesired green odour and taste. Based on chemical composition, the ham
      consistence appears improved by long-term dehydration, provided that protein
      breakdown is under control. It is concluded that for salt reduction of up to 25%
      to be achieved without negative side effects, extended ageing and restrained
      proteolysis are key factors.

PMID- 21955983
TI  - Characteristic transformation of humic acid during photoelectrocatalysis process
      and its subsequent disinfection byproduct formation potential.
AB  - In this study, degradation of humic acid (HA) via photoelectrocatalysis (PEC)
      process and corresponding disinfection byproduct formation potential (DBPFP) were
      investigated. Particularly, structure variation and subsequent DBPFP of HA during
      PEC treatment were correlated. The PEC process was found to be effective in
      reducing dissolved organic carbon concentration by 75.0% and UV absorbance at 254
      nm by 92.0%. Furthermore, 90.3% of haloacetic acids formation potential and 89.8%
      of trihalomethanes formation potential were reduced within 180 min. Based on
      molecular weight and resin fraction results, it was demonstrated that HA with
      large aromatic, hydrophobic and long aliphatic chain organics were transformed
      into small and hydrophilic organics during PEC process. Combined with the fourier
      transform infrared spectra and (13)C nuclear magnetic resonance spectra analysis
      of HA fractions, it was concluded that phenolic hydroxyl and conjugated double
      bonds tended to be attacked by hydroxyl radicals during PEC process; these groups
      were reactive with chlorine to produce disinfection byproducts (DBP), especially
      trihalomethane and trichloroacetic acid. By contrast, amino, carboxyl and
      alcoholic hydroxyl groups were relatively difficult to be oxidized during PEC
      process; these groups had the potential to form dichloroacetic acid during
      chlorination. Results of these studies confirmed that PEC process was a safe and
      effective technique to decrease DBP formation significantly in water treatment
      plant.

PMID- 21955984
TI  - Dynamic and distribution of ammonia-oxidizing bacteria communities during sludge
      granulation in an anaerobic-aerobic sequencing batch reactor.
AB  - The structure dynamic of ammonia-oxidizing bacteria (AOB) community and the
      distribution of AOB and nitrite-oxidizing bacteria (NOB) in granular sludge from
      an anaerobic-aerobic sequencing batch reactor (SBR) were investigated. A
      combination of process studies, molecular biotechniques and microscale techniques
      were employed to identify and characterize these organisms. The AOB community
      structure in granules was substantially different from that of the initial
      pattern of the inoculants sludge. Along with granules formation, the AOB
      diversity declined due to the selection pressure imposed by process conditions.
      Denaturing gradient gel electrophoresis (DGGE) and sequencing results
      demonstrated that most of Nitrosomonas in the inoculating sludge were remained
      because of their ability to rapidly adapt to the settling-washing out action.
      Furthermore, DGGE analysis revealed that larger granules benefit more AOB species
      surviving in the reactor. In the SBR were various size granules coexisted,
      granule diameter affected the distribution range of AOB and NOB. Small and medium
      granules (d<0.6 mm) cannot restrict oxygen mass transfer in all spaces of the
      sludge. Larger granules (d>0.9 mm) can result in smaller aerobic volume fraction
      and inhibition of NOB growth. All these observations provide support to future
      studies on the mechanisms responsible for the AOB in granules systems.

PMID- 21955985
TI  - Genome-wide analysis of WRKY gene family in Cucumis sativus.
AB  - BACKGROUND: WRKY proteins are a large family of transcriptional regulators in
      higher plant. They are involved in many biological processes, such as plant
      development, metabolism, and responses to biotic and abiotic stresses. Prior to
      the present study, only one full-length cucumber WRKY protein had been reported.
      The recent publication of the draft genome sequence of cucumber allowed us to
      conduct a genome-wide search for cucumber WRKY proteins, and to compare these
      positively identified proteins with their homologs in model plants, such as
      Arabidopsis. RESULTS: We identified a total of 55 WRKY genes in the cucumber
      genome. According to structural features of their encoded proteins, the cucumber
      WRKY (CsWRKY) genes were classified into three groups (group 1-3). Analysis of
      expression profiles of CsWRKY genes indicated that 48 WRKY genes display
      differential expression either in their transcript abundance or in their
      expression patterns under normal growth conditions, and 23 WRKY genes were
      differentially expressed in response to at least one abiotic stresses (cold,
      drought or salinity). The expression profile of stress-inducible CsWRKY genes
      were correlated with those of their putative Arabidopsis WRKY (AtWRKY) orthologs,
      except for the group 3 WRKY genes. Interestingly, duplicated group 3 AtWRKY genes
      appear to have been under positive selection pressure during evolution. In
      contrast, there was no evidence of recent gene duplication or positive selection
      pressure among CsWRKY group 3 genes, which may have led to the expressional
      divergence of group 3 orthologs. CONCLUSIONS: Fifty-five WRKY genes were
      identified in cucumber and the structure of their encoded proteins, their
      expression, and their evolution were examined. Considering that there has been
      extensive expansion of group 3 WRKY genes in angiosperms, the occurrence of
      different evolutionary events could explain the functional divergence of these
      genes.

PMID- 21955986
TI  - Characterization of a new ARID family transcription factor (Brightlike/ARID3C)
      that co-activates Bright/ARID3A-mediated immunoglobulin gene transcription.
AB  - Two members, Bright/ARID3A and Bdp/ARID3B, of the ARID (AT-Rich Interaction
      Domain) transcription family are distinguished by their ability to specifically
      bind to DNA and to self-associate via a second domain, REKLES. Bright and Bdp
      positively regulate immunoglobulin heavy chain gene (IgH) transcription by
      binding to AT-rich motifs within Matrix Associating Regions (MARs) residing
      within a subset of V(H) promoters and the EMU intronic enhancer. In addition,
      REKLES provides Bright nuclear export function, and a small pool of Bright is
      directed to plasma membrane sub-domains/lipid rafts where it associates with and
      modulates signaling of the B cell antigen receptor (BCR). Here, we characterize a
      third, highly conserved, physically condensed ARID3 locus, Brightlike/ARID3C.
      Brightlike encodes two alternatively spliced, SUMO-I-modified isoforms that
      include or exclude (Delta6) the REKLES-encoding exon 6. Brightlike transcripts
      and proteins are expressed preferentially within B lineage lymphocytes and
      coordinate with highest Bright expression in activated follicular B cells.
      Brightlike, but not BrightlikeDelta6, undergoes nuclear-cytoplasmic shuttling
      with a fraction localizing within lipid rafts following BCR stimulation.
      Brightlike, but not BrightlikeDelta6, associates with Bright in solution, at
      common DNA binding sites in vitro, and is enriched at Bright binding sites in
      chromatin. Although possessing little transactivation capacity of its own,
      Brightlike significantly co-activates Bright-dependent IgH transcription with
      maximal activity mediated by the unsumoylated form. In sum, this report
      introduces Brightlike as an additional functional member of the family of ARID
      proteins, which should be considered in regulatory circuits, previously ascribed
      to be mediated by Bright.

PMID- 21955987
TI  - Tumor-expressed collagens can modulate immune cell function through the
      inhibitory collagen receptor LAIR-1.
AB  - Many tumor types over-express collagens, what correlates with enhanced metastatic
      capacity and unfavorable clinical outcome. This is generally explained by the
      importance of collagens in creating a microenvironment that supports tumor cell
      survival and enhances cell migration. Importantly, collagens act as ligands for
      the inhibitory receptor LAIR-1, which inhibits the function of multiple types of
      immune cells. Here we propose a new role for tumor expressed collagens and show
      that these structural proteins can be exploited by tumor cells to inhibit immune
      responses through an interaction with LAIR-1. We show that both LAIR-1-Fc fusion
      proteins and LAIR-1 expressing cells bind to transmembrane collagens expressed by
      tumor cells. Interference with collagen expression by specific knock-down of
      prolyl 4-hydroxylase diminishes LAIR-1 binding to tumor cells, demonstrating the
      specificity of the interaction. Consistently, both transmembrane collagens and
      extracellular collagens produced by multiple tumor cell types can activate LAIR
      1. Furthermore, overexpression of collagen XVII on target cells results in
      diminished NK cell cytotoxic activity. Thus tumor-expressed collagens can bind
      and trigger immune inhibitory signaling via LAIR-1, suggesting that collagens
      indeed may affect tumor immune evasion.

PMID- 21955988
TI  - Visual prognosis and spectral-domain optical coherence tomography findings of
      myopic foveoschisis surgery using 25-gauge transconjunctival sutureless
      vitrectomy.
AB  - PURPOSE: To identify spectral-domain optical coherence tomography findings
      related to visual outcome in myopic foveoschisis after 25-gauge transconjunctival
      sutureless vitrectomy. METHODS: Thirty-eight eyes with myopic foveoschisis were
      prospectively followed-up to 6 months after vitrectomy. Best-corrected visual
      acuity (BCVA), axial length, and spectral-domain optical coherence tomography
      findings were analyzed for identification of factors affecting visual outcome.
      RESULTS: Best-corrected visual acuity improved significantly (preoperative 0.841
      +/- 0.534 logarithm of minimal angle of resolution to postoperative 0.532 +/-
      0.536 logarithm of minimal angle of resolution, P = 0.001), and central retinal
      thickness showed significant reduction (preoperative 409 +/- 143 MUm to
      postoperative 259 +/- 72 MUm, P < 0.001) with surgery. Anatomical success was
      achieved in 34/38 eyes (89.5%). Photoreceptor layer disruption was found in 20 of
      38 eyes (52.6%) preoperatively and persisted after surgery in 18 of 20 eyes
      (90.0%). Patients with preoperative photoreceptor layer defects had significantly
      more associated foveal detachments and irregular choroidal surfaces and worse
      preoperative and final best-corrected visual acuity. Preoperative best-corrected
      visual acuity showed significant correlation with final best-corrected visual
      acuity (Pearson correlation coefficient = 0.555, P = 0.001). Patients with
      irregular choroidal surfaces and photoreceptor layer disruption had significantly
      worse final best-corrected visual acuity (P = 0.035, 0.005). CONCLUSION: Twenty
      five-gauge transconjunctival sutureless vitrectomy showed favorable results for
      the management of myopic foveoschisis. Photoreceptor layer defects and irregular
      choroidal surfaces on spectral-domain optical coherence tomography persist
      despite surgery, limiting visual outcome.

PMID- 21955989
TI  - Early controlled drainage of massive suprachoroidal hemorrhage with the aid of an
      expanding gas bubble and risk factors.
AB  - PURPOSE: To assess the visual outcome after massive suprachoroidal hemorrhage
      managed by early controlled drainage using the aid of an intravitreal expanding
      gas bubble (100% perfluoropropane). The ocular and systemic risk factors were
      also reviewed. METHODS: Data were obtained retrospectively from patients with
      massive suprachoroidal hemorrhage who were treated in Worthing and Southlands
      National Health Service Trust between January 2003 and December 2008. RESULTS:
      The study included 10 patients (5 women and 5 men) with a mean age of 73.9 years
      (range, 54-84 years). All patients underwent early controlled drainage of massive
      suprachoroidal hemorrhage using 100% perfluoropropane as a tamponade. The mean
      interval of drainage from the onset was 3.5 days (range, 1-10 days). Anatomical
      restoration of ocular structures was achieved in 7 patients, with good final
      visual outcome at mean 9 months (range, 6-14 months). The remaining three
      patients had poor visual outcome because of retinal detachment with proliferative
      vitreoretinopathy. The most common risk factor in this case series was glaucoma,
      which was seen in five patients. Arteriosclerosis was the only risk factor in two
      patients. CONCLUSION: Early controlled drainage of massive suprachoroidal
      hemorrhage with 100% perfluoropropane tamponade may help in achieving a good
      visual outcome. The use of 100% perfluoropropane has the advantage of maintaining
      positive pressure while facilitating controlled drainage of the hemorrhage as the
      clot lyses. Retinal detachment however is a poor prognostic indicator.
      Arteriosclerosis and glaucoma were the most common risk factors seen in this case
      series.

PMID- 21955991
TI  - Co-habiting amphibian species harbor unique skin bacterial communities in wild
      populations.
AB  - Although all plant and animal species harbor microbial symbionts, we know
      surprisingly little about the specificity of microbial communities to their
      hosts. Few studies have compared the microbiomes of different species of animals,
      and fewer still have examined animals in the wild. We sampled four pond habitats
      in Colorado, USA, where multiple amphibian species were present. In total, 32
      amphibian individuals were sampled from three different species including
      northern leopard frogs (Lithobates pipiens), western chorus frogs (Pseudacris
      triseriata) and tiger salamanders (Ambystoma tigrinum). We compared the diversity
      and composition of the bacterial communities on the skin of the collected
      individuals via barcoded pyrosequencing of the 16S rRNA gene. Dominant bacterial
      phyla included Acidobacteria, Actinobacteria, Bacteriodetes, Cyanobacteria,
      Firmicutes and Proteobacteria. In total, we found members of 18 bacterial phyla,
      comparable to the taxonomic diversity typically found on human skin. Levels of
      bacterial diversity varied strongly across species: L. pipiens had the highest
      diversity; A. tigrinum the lowest. Host species was a highly significant
      predictor of bacterial community similarity, and co-habitation within the same
      pond was not significant, highlighting that the skin-associated bacterial
      communities do not simply reflect those bacterial communities found in their
      surrounding environments. Innate species differences thus appear to regulate the
      structure of skin bacterial communities on amphibians. In light of recent
      discoveries that some bacteria on amphibian skin have antifungal activity, our
      finding suggests that host-specific bacteria may have a role in the species
      specific resistance to fungal pathogens.

PMID- 21955992
TI  - Sunlight modulates the relative importance of heterotrophic bacteria and
      picophytoplankton in DMSP-sulphur uptake.
AB  - There is a large body of evidence supporting a major role of heterotrophic
      bacteria in dimethylsulphoniopropionate (DMSP) utilisation as a source of reduced
      sulphur. However, a role for phototrophic microorganisms has been only recently
      described and little is known about their contribution to DMSP consumption and
      the potential modulating effects of sunlight. In an attempt to ascertain the
      relative quantitative roles of heterotrophic bacteria and picophytoplankton in
      the osmoheterotrophic uptake of DMSP-sulphur upon exposure to natural sunlight
      conditions, we incubated northwestern Mediterranean waters under various optical
      filters and used an array of bulk and single-cell activity methods to trace the
      fate of added (35)S-DMSP. Flow cytometry cell sorting confirmed dark (35)S uptake
      by Prochlorococcus, Synechococcus and heterotrophic bacteria, the latter being
      the most efficient in terms of uptake on a cell volume basis. Under exposure to
      full sunlight, however, the relative contribution of Synechococcus was
      significantly enhanced, mainly because of the inhibition of heterotrophic
      bacteria. Microautoradiography showed a strong increase in the proportion of
      Synechococcus cells actively taking up (35)S-DMSP, which, after full sunlight
      exposure, made up to 15% of total active Bacteria. Parallel incubations with (3)H
      leucine generally showed no clear responses to light. Finally, size-fractionated
      assimilation experiments showed greater relative cyanobacterial assimilation
      during the day than at night compared with that of heterotrophic bacteria. Our
      results show for the first time a major influence of sunlight in regulating the
      competition among autotrophic and heterotrophic picoplankton for DMSP uptake at
      both the daily and seasonal time scales.

PMID- 21955993
TI  - Shifts in bacterial communities of two Caribbean reef-building coral species
      affected by white plague disease.
AB  - Coral reefs are deteriorating at an alarming rate mainly as a consequence of the
      emergence of coral diseases. The white plague disease (WPD) is the most prevalent
      coral disease in the southwestern Caribbean, affecting dozens of coral species.
      However, the identification of a single causal agent has proved problematic. This
      suggests more complex etiological scenarios involving alterations in the dynamic
      interaction between environmental factors, the coral immune system and the
      symbiotic microbial communities. Here we compare the microbiome of healthy and
      WPD-affected corals from the two reef-building species Diploria strigosa and
      Siderastrea siderea collected at the Tayrona National Park in the Caribbean of
      Colombia. Microbiomes were analyzed by combining culture-dependent methods and
      pyrosequencing of 16S ribosomal DNA (rDNA) V5-V6 hypervariable regions. A total
      of 20,410 classifiable 16S rDNA sequences reads were obtained including all
      samples. No significant differences in operational taxonomic unit diversity were
      found between healthy and affected tissues; however, a significant increase of
      Alphaproteobacteria and a concomitant decrease in the Beta- and
      Gammaproteobacteria was observed in WPD-affected corals of both species.
      Significant shifts were also observed in the orders Rhizobiales,
      Caulobacteriales, Burkholderiales, Rhodobacterales, Aleteromonadales and
      Xanthomonadales, although they were not consistent between the two coral species.
      These shifts in the microbiome structure of WPD-affected corals suggest a loss of
      community-mediated growth control mechanisms on bacterial populations specific
      for each holobiont system.

PMID- 21955994
TI  - Phytoplankton distribution patterns in the northwestern Sargasso Sea revealed by
      small subunit rRNA genes from plastids.
AB  - Phytoplankton species vary in their physiological properties, and are expected to
      respond differently to seasonal changes in water column conditions. To assess
      these varying distribution patterns, we used 412 samples collected monthly over
      12 years (1991-2004) at the Bermuda Atlantic Time-Series Study site, located in
      the northwestern Sargasso Sea. We measured plastid 16S ribosomal RNA gene
      abundances with a terminal restriction fragment length polymorphism approach and
      identified distribution patterns for members of the Prymnesiophyceae,
      Pelagophyceae, Chrysophyceae, Cryptophyceae, Bacillariophyceae and
      Prasinophyceae. The analysis revealed dynamic bloom patterns by these
      phytoplankton taxa that begin early in the year, when the mixed layer is deep.
      Previously, unreported open-ocean prasinophyte blooms dominated the plastid gene
      signal during convective mixing events. Quantitative PCR confirmed the blooms and
      transitions of Bathycoccus, Micromonas and Ostreococcus populations. In contrast,
      taxa belonging to the pelagophytes and chrysophytes, as well as cryptophytes,
      reached annual peaks during mixed layer shoaling, while Bacillariophyceae
      (diatoms) were observed only episodically in the 12-year record. Prymnesiophytes
      dominated the integrated plastid gene signal. They were abundant throughout the
      water column before mixing events, but persisted in the deep chlorophyll maximum
      during stratified conditions. Various models have been used to describe
      mechanisms that drive vernal phytoplankton blooms in temperate seas. The range of
      taxon-specific bloom patterns observed here indicates that different 'spring
      bloom' models can aptly describe the behavior of different phytoplankton taxa at
      a single geographical location. These findings provide insight into the
      subdivision of niche space by phytoplankton and may lead to improved predictions
      of phytoplankton responses to changes in ocean conditions.

PMID- 21955990
TI  - Novel lineages of Prochlorococcus and Synechococcus in the global oceans.
AB  - Picocyanobacteria represented by Prochlorococcus and Synechococcus have an
      important role in oceanic carbon fixation and nutrient cycling. In this study, we
      compared the community composition of picocyanobacteria from diverse marine
      ecosystems ranging from estuary to open oceans, tropical to polar oceans and
      surface to deep water, based on the sequences of 16S-23S rRNA internal
      transcribed spacer (ITS). A total of 1339 ITS sequences recovered from 20 samples
      unveiled diverse and several previously unknown clades of Prochlorococcus and
      Synechococcus. Six high-light (HL)-adapted Prochlorococcus clades were
      identified, among which clade HLVI had not been described previously.
      Prochlorococcus clades HLIII, HLIV and HLV, detected in the Equatorial Pacific
      samples, could be related to the HNLC clades recently found in the high-nutrient,
      low-chlorophyll (HNLC), iron-depleted tropical oceans. At least four novel
      Synechococcus clades (out of six clades in total) in subcluster 5.3 were found in
      subtropical open oceans and the South China Sea. A niche partitioning with depth
      was observed in the Synechococcus subcluster 5.3. Members of Synechococcus
      subcluster 5.2 were dominant in the high-latitude waters (northern Bering Sea and
      Chukchi Sea), suggesting a possible cold-adaptation of some marine Synechococcus
      in this subcluster. A distinct shift of the picocyanobacterial community was
      observed from the Bering Sea to the Chukchi Sea, which reflected the change of
      water temperature. Our study demonstrates that oceanic systems contain a large
      pool of diverse picocyanobacteria, and further suggest that new genotypes or
      ecotypes of picocyanobacteria will continue to emerge, as microbial consortia are
      explored with advanced sequencing technology.

PMID- 21955995
TI  - Gene expression profile of the cartilage tissue spontaneously regenerated in vivo
      by using a novel double-network gel: comparisons with the normal articular
      cartilage.
AB  - BACKGROUND: We have recently found a phenomenon that spontaneous regeneration of
      a hyaline cartilage-like tissue can be induced in a large osteochondral defect by
      implanting a double-network (DN) hydrogel plug, which was composed of poly-(2
      Acrylamido-2-methylpropanesulfonic acid) and poly-(N, N'-Dimetyl acrylamide), at
      the bottom of the defect. The purpose of this study was to clarify gene
      expression profile of the regenerated tissue in comparison with that of the
      normal articular cartilage. METHODS: We created a cylindrical osteochondral
      defect in the rabbit femoral grooves. Then, we implanted the DN gel plug at the
      bottom of the defect. At 2 and 4 weeks after surgery, the regenerated tissue was
      analyzed using DNA microarray and immunohistochemical examinations. RESULTS: The
      gene expression profiles of the regenerated tissues were macroscopically similar
      to the normal cartilage, but showed some minor differences. The expression degree
      of COL2A1, COL1A2, COL10A1, DCN, FMOD, SPARC, FLOD2, CHAD, CTGF, and COMP genes
      was greater in the regenerated tissue than in the normal cartilage. The top 30
      genes that expressed 5 times or more in the regenerated tissue as compared with
      the normal cartilage included type-2 collagen, type-10 collagen, FN, vimentin,
      COMP, EF1alpha, TFCP2, and GAPDH genes. CONCLUSIONS: The tissue regenerated by
      using the DN gel was genetically similar but not completely identical to
      articular cartilage. The genetic data shown in this study are useful for future
      studies to identify specific genes involved in spontaneous cartilage
      regeneration.

PMID- 21955997
TI  - Specific detection of Campylobacter jejuni using the bacteriophage NCTC 12673
      receptor binding protein as a probe.
AB  - Campylobacter jejuni is found in the intestines of poultry, cattle, swine, wild
      birds and pet animals and is the major cause of foodborne gastroenteritis in
      developed countries. We report the use of the receptor binding protein (RBP) of
      Campylobacter bacteriophage NCTC 12673 for the specific capture of Campylobacter
      jejuni bacteria using RBP-derivatized capturing surfaces. The Gp48 RBP was
      expressed as a glutathione S-transferase-Gp48 (GST-Gp48) fusion protein and
      immobilized onto surface plasmon resonance (SPR) surfaces using glutathione self
      assembled monolayers (GSH SAM). Bovine serum albumin (BSA) was used to block any
      non-specific binding. Glutathione SAM leads to an oriented attachment of the
      protein, resulting in a two- to three-fold improvement of bacterial capture when
      compared to dithiobis(succinimidyl propionate) (DTSP) SAM-based unoriented
      attachment. The specificity of recognition was confirmed using Salmonella
      enterica subsp. enterica serovar Typhimurium as a negative control, which indeed
      showed negligible binding. The detection limit of the RBP-derivatized SPR
      surfaces was found to be 10(2) cfu/ml. Finally, GST-Gp48 was also immobilized
      onto magnetic beads that were successfully used to capture and pre-concentrate
      the host pathogen from suspension.

PMID- 21955998
TI  - Antiepidermal growth factor receptor monoclonal antibody improves survival
      outcomes in the treatment of patients with metastatic colorectal cancer.
AB  - The aim of this study was to determine whether or not the addition of anti
      epidermal growth factor receptor (anti-EGFR) monoclonal antibody (mAb) to
      standard chemotherapy or best supportive care (BSC), compared with chemotherapy
      or BSC alone, can improve overall survival (OS) and progression-free survival
      (PFS) in patients with metastatic colorectal cancer (mCRC), and evaluate the
      influence of KRAS mutant status on the efficacy of anti-EGFR mAb. Medline,
      Embase, the Cochrane controlled trials register, and the Science Citation Index
      were searched. Nine trials were identified, covering a total of 7941 patients.
      The treatment of mCRC with a combination of anti-EGFR mAb and chemotherapy or
      BSC, as compared with chemotherapy or BSC alone, improved the OS [hazard ratio
      (HR), 0.90 (0.84-0.96); P=0.002]. The benefit of anti-EGFR mAb in patients with
      KRAS wild-type tumors was apparent in relation to a marginal trend toward
      improved OS [HR, 0.84 (0.70-1.01); P=0.06], and significantly improved PFS [HR,
      0.64 (0.51-0.81); P<0.001]. No benefit for the addition of anti-EGFR mAb was
      detected for any efficacy end-point in patients with KRAS mutant tumors. The
      summary HRs (anti-EGFR mAb vs control) were 0.98 (0.88-1.08) (P=0.71) for OS and
      1.08 (0.94-1.25) (P=0.27) for PFS, respectively. In conclusion, this analysis
      provides confirmation that, compared with chemotherapy or BSC alone, anti-EGFR
      mAb with chemotherapy or BSC reduces the risk of progression and death of mCRC
      and that this benefit is seen only in patients with wild-type KRAS tumors.

PMID- 21955999
TI  - Cytotoxicity of human recombinant arginase I (Co)-PEG5000 in the presence of
      supplemental L-citrulline is dependent on decreased argininosuccinate synthetase
      expression in human cells.
AB  - Human recombinant arginase I cobalt [HuArgI (Co)] coupled with polyethylene
      glycol 5000 [HuArgI (Co)-PEG5000] has shown potent in-vitro depletion of arginine
      from tissue culture medium. We now show that HuArgI (Co)-PEG5000 is toxic to
      almost all cancer cell lines and to some normal primary cells examined. In
      contrast, HuArgI (Co)-PEG5000 in combination with supplemental L-citrulline is
      selectively cytotoxic to a fraction of human cancer cell lines in tissue culture,
      including some melanomas, mesotheliomas, acute myeloid leukemias, hepatocellular
      carcinomas, pancreas adenocarcinomas, prostate adenocarcinomas, lung
      adenocarcinomas, osteosarcomas, and small cell lung carcinomas. Unfortunately, a
      subset of normal human tissues is also sensitive to HuArgI (Co)-PEG5000 with L
      citrulline supplementation, including umbilical endothelial cells, bronchial
      epithelium, neurons, and renal epithelial cells. We further show that cell
      sensitivity is predicted by the level of cellular argininosuccinate synthetase
      protein expression measured by immunoblots. By comparing a 3-day and 7-day
      exposure to HuArgI (Co)-PEG5000 with supplemental L-citrulline, some tumor cells
      sensitive on short-term assay are resistant in the 7-day assay consistent with
      the induction of argininosuccinate synthetase expression. On the basis of these
      results, we hypothesize that HuArgI (Co)-PEG5000 in combination with L-citrulline
      supplementation may be an attractive therapeutic agent for some argininosuccinate
      synthetase-deficient tumors. These in-vitro findings stimulate further
      development of this molecule and may aid in the identification of tissue
      toxicities and better selection of patients who will potentially respond to this
      combination therapy.

PMID- 21955996
TI  - Endosomal transport via ubiquitination.
AB  - Cell survival, growth, differentiation and homeostasis rely on exquisite control
      of the abundance of particular cell-surface membrane proteins. Cell-surface
      proteins must respond appropriately to environmental and intracellular cues,
      often undergoing regulated internalization and lysosomal degradation. These
      proteins also can sustain damage and must be recognized and removed. A unifying
      mechanism has emerged for the trafficking of damaged and downregulated proteins
      to the lysosome by their attachment to ubiquitin (Ub), which serves as a sorting
      signal for clathrin-mediated internalization and sorting into late endosomes.
      Major questions remain as to how this system is governed, how it is adapted for
      different proteins, and whether Ub serves as more than a one-way ticket to the
      lysosome for degradation. Here, we highlight recent insights and the challenges
      that remain.

PMID- 21956000
TI  - Unconscious semantic activation depends on feature-specific attention allocation.
AB  - We examined whether semantic activation by subliminally presented stimuli is
      dependent upon the extent to which participants assign attention to specific
      semantic stimulus features and stimulus dimensions. Participants pronounced
      visible target words that were preceded by briefly presented, masked prime words.
      Both affective and non-affective semantic congruence of the prime-target pairs
      were manipulated under conditions that either promoted selective attention for
      affective stimulus information or selective attention for non-affective semantic
      stimulus information. In line with our predictions, results showed that affective
      congruence had a clear impact on word pronunciation latencies only if
      participants were encouraged to assign attention to the affective stimulus
      dimension. In contrast, non-affective semantic relatedness of the prime-target
      pairs produced no priming at all. Our findings are consistent with the hypothesis
      that unconscious activation of (affective) semantic information is modulated by
      feature-specific attention allocation.

PMID- 21956001
TI  - Closing information gaps with shared electronic patient summaries: how much will
      it matter?
AB  - BACKGROUND: Information deficits contribute to medical errors. Hence several
      efforts to develop electronic communication systems to facilitate a flow of
      information between health care providers have been attempted, including
      initiatives to develop regional or national electronic patient summaries.
      OBJECTIVES: To study information access and information needs in inpatient
      emergency departments, and how clinicians in these departments handle deficits in
      available information. METHODS: We conducted an observational study of
      consecutive unplanned inpatient admissions using a structured form to register a
      set of predefined parameters and free-text notes, including a post-examination
      interview with the examining emergency department doctors and nurses. RESULTS: We
      observed 177 patient admissions, excluding any patients under 18 years of age and
      planned admissions. One in four patients arrived without any referral. Nearly all
      referrals described the presenting complaint with a tentative diagnosis. One
      third of the referrals lacked medication record and medical history. Only one in
      ten referrals contained information about contraindications. If the patient had
      previously been admitted to the hospital, the emergency department doctors used
      the existing electronic patient record and seemed to favor previous discharge
      letters as an information source. Information on current medications was often
      copied from earlier admissions. In half of the cases the patients also provided
      supplementary information in other ways not available, though one in five
      patients was not in a cognitive state to be properly interviewed. The examining
      doctors reported a lack of crucial information in 10% of the observed referrals.
      CONCLUSION: Overall, information about medications and previous history was
      described in most referrals, but was still the information most frequently
      inquired or searched for. Qualitative assessments revealed that insufficient
      information put a significant stress on both patients and staff, and in turn
      caused additional workload and risky work-arounds. In our assessment, these
      information deficits could be effectively mitigated by an up to date easy-access
      patient summary.

PMID- 21956002
TI  - Does the introduction of an electronic nursing documentation system in a nursing
      home reduce time on documentation for the nursing staff?
AB  - PURPOSE: To determine whether the introduction of an electronic nursing
      documentation system in a nursing home reduces the proportion of time nursing
      staff spend on documentation, and to use this information in evaluating the
      usefulness of the system in improving the work of nursing staff. METHODS: An
      observational work sampling study was conducted in 2009 and 2010, 2 months
      before, and 3, 6 and 12 months after the introduction of an electronic nursing
      documentation system. An observer (ENM) used a work classification tool to record
      documentation activities being performed using paper and with a computer by
      nursing staff at particular times for periods of 5 days. RESULTS: Three hundred
      and eighty three (383) activities were recorded before implementation of the
      electronic system, 472 activities at 3 months, 502 at 6 months, and 338 at 12
      months after implementation. There was no significant difference between the
      proportion of time nursing staff spent on documentation 2 months before and 3
      months after the implementation of the electronic system. Six months after
      implementation, the proportion of time on documentation increased significantly
      and after 12 months, settled back to original levels that were recorded in the
      paper-based system. Over half of the proportion of time on documentation at 6 and
      12 months after implementation was spent on paper documentation tasks.
      CONCLUSION: Introduction of an electronic nursing documentation system did not
      reduce the proportion of time nursing staff spent on documentation. This may in
      part have been a result of the practice of documenting some information items on
      paper and others on a computer. To reduce the use of paper documentation or to
      achieve a paper-free documentation environment in this setting, an in-depth
      understanding of nursing staff's information needs, and documentation workflow is
      necessary.

PMID- 21956003
TI  - A study on Singaporean women's acceptance of using mobile phones to seek health
      information.
AB  - OBJECTIVE: This paper is an exploratory study that investigates Singaporean
      women's acceptance of using mobile phones to seek health information. METHOD: A
      mobile web containing health topics was developed to track Singaporean women's
      actual use of their mobile phones to seek health information. A survey
      questionnaire measured variables hypothesized to predict Behavioural Intention.
      The survey responses were then matched to the data collected on actual use.
      Correlation analysis and hierarchical regression were used to analyze the data
      collected. RESULTS: Findings revealed that Perceived Usefulness and Self-efficacy
      positively predicted the intention to use mobile phones to seek health
      information. The study also confirmed the presence of an intention-behaviour gap
      among participants. The conversion of intention to actual behaviour hinges on
      technical concerns and design factors. Prior experiences with health information
      seeking reinforced women's evaluations of the usefulness of the mobile web
      application and helped them to feel more self-efficacious about using their
      mobile phones to seek health information. Using mobile phones to seek health
      information was found to be complementary to online health information seeking
      and can be regarded as an alternative source to the internet for seeking health
      information. CONCLUSION: This study contributes to the existing literature by
      applying the Technology Acceptance Model (TAM) in the context of mobile health
      information seeking, for which there has been a lack of studies, and demonstrated
      that the inclusion of additional variables can enhance TAM's predictive power.
      The empirical presence of an intention-behaviour gap calls for future research to
      investigate the reasons behind the gap. Finally, the findings from this study can
      serve as input to promote women's use of mobile phones for better self-management
      of health.

PMID- 21956004
TI  - Physicians' experiences of participation in healthcare IT development in Finland:
      willing but not able.
AB  - OBJECTIVE: To learn (1) about the kind of experiences that physicians have with
      participation in healthcare IT development; (2) whether physicians are interested
      in participating in IT development activities, and if so, how; and (3) the
      visions that physicians have regarding future IT systems. METHODS: A web-based
      questionnaire which was answered by about one-third of the working-age physicians
      in Finland, which is exceptionally broad and sizeable a sample. This research
      deals with only a small part of the entire questionnaire. The questions used for
      this study were both quantitative and qualitative. Statistical methods were
      applied to the former and content analysis to the latter. RESULTS: The responding
      physicians were highly critical of their IT systems, and their experiences with
      the current methods of participation, or rather the lack of it, were quite
      negative. However, a very significant proportion of the respondents were willing
      to contribute to IT systems development, contrary to a common assumption that
      clinicians are disinterested. Visioning of future systems was quite cautious,
      dealing mainly with usability improvements to the current systems. CONCLUSIONS:
      Major improvements are needed both in the usability of the systems currently in
      use in Finland and in the collaboration between end-users and developers.
      Improved methods of participation need to be developed and applied, particularly
      for the procurement, deployment and on-going development of commercial-off-the
      shelf applications.

PMID- 21956005
TI  - Arthroereisis of the subtalar joint: an uncommon complication and literature
      review.
AB  - Arthroereisis is an operation to prevent abnormal pronation in the subtalar joint
      in children and adults with symptomatic flexible flatfeet. In the present report,
      we describe an uncommon late complication of a former variation of this
      procedure, namely the case of an adult male who experienced migration of a
      xenogeneic bone graft that had been implanted 55 years earlier. A thorough review
      of the existing data was also undertaken to better understand the complications
      of this procedure.

PMID- 21956006
TI  - Using the book teaching IOM as a structure for improved care and practice in home
      healthcare.

PMID- 21956007
TI  - Supporting the need for home care by mothers of children with hemophilia.
AB  - This research is a descriptive study that took place in Turkey and was intended
      to determine the difficulties experienced by mothers of children with hemophilia
      in maintaining their care at home and establishing appropriate interventions.
      Research data were collected using a survey prepared by the researchers after
      reviewing the existing literature. The survey contained 2 sections: (a) questions
      about the mothers' sociodemographic data and (b) 5 questions about the
      difficulties that mothers with hemophiliac children experience. Mothers were
      observed to have not received education about accidents and first aid and were
      afraid that their child would have an accident (55%); they experienced difficulty
      finding medications (75%); they felt they needed healthcare personnel during
      medication administration (85%); and they were sad that their child was ill
      (80%). Pediatric haematology nurses should strive to educate mothers with
      hemophiliac children about the disease and how to deal with accidents, first aid,
      and medication administration; home care services should be organized and made
      available for all hemophiliac children and their families.

PMID- 21956008
TI  - Preventing avoidable hospitalizations.
AB  - To reduce avoidable hospital readmissions and improve transitions between
      healthcare settings, Virtua Home Care implemented a Transitions of Care Program
      based on the Transitional Care Model developed at the University of Pennsylvania
      School of Nursing. Home care nurses were educated to be transitional care nurses
      and provided intensive education and follow-up for patients with chronic diseases
      who were identified as having a high risk of readmission. This program, which
      provides services to patients enrolled in fee-for-service (FFS) Medicare and who
      are eligible to receive the home health benefit, has successfully reduced
      hospital readmissions. This article describes Virtua Home Care's journey in
      adapting and implementing an evidence-based care transitions model.

PMID- 21956009
TI  - Assessment of surgical wounds in the home health patient: definitions and
      accuracy with OASIS-C.
AB  - The number of surgical patients receiving home care continues to grow as
      hospitals discharge patients sooner. Home health clinicians must gain knowledge
      of the wound healing stages and surgical wound classification to collect accurate
      data in the Outcome and Assessment Information Set-C (OASIS-C). This article
      provides the information clinicians need to accurately assess surgical wounds and
      implement best practices for improving surgical wounds in the home health
      patient.

PMID- 21956011
TI  - Chronic pancreatitis: an update for home care and hospice clinicians.
AB  - Chronic pancreatitis is a relentlessly painful condition associated most commonly
      with alcoholism. Patients suffer wasting and depression as a result of chronic
      pain. It is important for home care clinicians to recognize the signs of
      pancreatitis and understand the current evidence-based treatment strategies to
      control the symptoms. Although alcoholism and depression are frequent
      comorbidities of pancreatitis, a full discussion of alcoholism and depression is
      outside the scope of this article.

PMID- 21956013
TI  - Reduction of pressure ulcer incidence in the home healthcare setting: a pressure
      relief seating cushion project to reduce the number of community-acquired
      pressure ulcers.
AB  - The development of pressure ulcers is a quality of care and cost issue across the
      healthcare continuum. Evidence-based practice includes pressure relief, but
      homebound elderly people at risk for developing pressure ulcers do not qualify to
      receive a pressure-relief seating surface under Medicare unless they have a
      wheelchair. A project was initiated to obtain and provide pressure-relief seat
      cushions for this at-risk population. The overall purpose of this project was to
      reduce the incidence of community-acquired pressure ulcers using evidence-based
      practice.

PMID- 21956014
TI  - Evidence-based care, best practices, and OASIS-C.

PMID- 21956016
TI  - Impact of kidney cancer surgery on oncologic and kidney functional outcomes.
AB  - Kidney cancer is a common genitourinary malignancy. The incidence of kidney
      cancer has progressively increased in the past few decades, with the greatest
      increase noted for incidentally discovered small renal masses. Along with the
      change in presentation and diagnosis of kidney cancer, surgical treatment of
      kidney cancer also has evolved dramatically during the past 5 decades, moving
      from universal use of radical extirpation to more frequent nephron-sparing and
      minimally invasive surgeries. This article reviews the contemporary management of
      localized kidney cancers and discusses the impact of surgery on oncologic and
      nononcologic outcomes.

PMID- 21956017
TI  - Lyme-associated orbital inflammation presenting as painless subacute unilateral
      ptosis.
AB  - A 90-year-old woman presented with subacute painless left ptosis. Examination of
      the left eye revealed ptosis with loss of the superior eyelid sulcus, 2 mm of
      proptosis, mild tenderness with retropulsion, and optic disc edema. Levator
      function and extraocular movements were normal, and there was no relative
      afferent pupillary defect. MRI demonstrated thickening of the extraocular muscles
      in the left orbit with lacrimal gland enlargement and mild enhancement of the
      optic nerve sheath. Serology revealed a positive enzyme-linked immunosorbent
      assay for Lyme antibodies and a positive Western blot of Lyme IgG titer. The
      patient recalled a tick bite 6 months earlier, at which time Lyme serologies were
      negative. After 3 weeks of intravenous ceftriaxone, she had a significant
      improvement and a full recovery by 3 months. Lyme disease should be included in
      the differential diagnosis of orbital inflammation, especially in Lyme-endemic
      areas.

PMID- 21956015
TI  - The role of phosphorus in the development and progression of vascular
      calcification.
AB  - Vascular calcification is associated with significant cardiovascular morbidity
      and mortality in patients with chronic kidney disease (CKD). Factors unique to
      patients with CKD, such as hyperphosphatemia, predispose these patients to early
      and progressive vascular calcification. Hyperphosphatemia appears to be involved
      in a number of mechanisms that trigger and advance the progression of vascular
      calcification, including (1) transition of vascular smooth muscle cells (VSMCs)
      from a contractile to an osteochondrogenic phenotype and mineralization of VSMC
      matrix through sodium-dependent phosphate cotransporters, (2) induction of VSMC
      apoptosis, (3) inhibition of monocyte/macrophage differentiation into osteoclast
      like cells, (4) elevation of fibroblast growth factor 23 levels, and (5)
      decreases in klotho expression. Whether vascular calcification can be prevented
      or reversed with strategies aimed at maintaining phosphate homeostasis presently
      is unknown. This review discusses these mechanisms in depth, exploring the
      interplay among vascular calcification promoters, inhibitors, and substrate that
      affect phosphorus handling leading to vascular calcification in individuals with
      CKD.

PMID- 21956018
TI  - Acute optic neuropathy associated with an intracranial mass in a patient with
      POEMS syndrome.
AB  - A 43-year-old man with POEMS syndrome (polyneuropathy, organomegaly,
      endocrinopathy, monoclonal gammopathy, and skin changes), including long-standing
      optic disc swelling, had sudden painless vision loss in the left eye. Brain MRI
      revealed an intracranial mass adjacent to the left optic nerve and enhancement of
      the optic nerve. The mass decreased in size following chemotherapy for myeloma
      with some recovery of vision. This represents a unique case of optic neuropathy
      due to presumed plasmacytoma in osteosclerotic IgA myeloma and POEMS syndrome.

PMID- 21956019
TI  - Importance of clinical judgment in the diagnosis of temporal (giant cell)
      arteritis.

PMID- 21956020
TI  - Simple and sensitive liquid chromatography-tandem mass spectrometry methods for
      quantification of paraquat in plasma and urine: application to experimental and
      clinical toxicological studies.
AB  - Simple, sensitive and specific liquid chromatography-tandem mass spectrometry (LC
      MS/MS) methods have been developed and validated for quantification of paraquat
      (PQ) in plasma and urine. Plasma and urine sample preparation were carried out by
      one-step protein precipitation using cold acetonitrile (-20 to -10  degrees C).
      After centrifugation, an aliquot of 10 MUL of supernatant was injected into a
      KinetexTM hydrophilic interaction chromatography (HILIC) column with a
      KrudKatcherTM Ultra in-line filter. The chromatographic separation was achieved
      using the mobile phase mixture of 250 mM ammonium formate (with 0.8% aqueous
      formic acid) in water and acetonitrile at a flow rate of 0.3 mL/min. Detection
      was performed using an API2000 triple quadrupole tandem mass spectrometer in
      multiple reaction monitoring (MRM) mode via an electrospray ionization (ESI)
      source. The calibration curve was linear over the concentration range of 10-5000
      ng/mL, with an LLOQ of 10 ng/mL. The inter- and intra-day precision (% R.S.D.)
      were <8.5% and 6.4% for plasma and urine, respectively with the accuracies (%)
      within the range of 95.1-102.8%. PQ in plasma and urine samples was stable when
      stored at -70  degrees C for three freeze-thaw cycles. The methods were
      successfully applied to determine PQ concentration in rat and human samples.

PMID- 21956021
TI  - Analysis of amantadine in biological fluids using hollow fiber-based liquid
      liquid-liquid microextraction followed by corona discharge ion mobility
      spectrometry.
AB  - A method based on liquid-liquid-liquid microextraction combined with corona
      discharge ion mobility spectrometry was developed for the analysis of amantadine
      in human urine and plasma samples. Amantadine was extracted from alkaline aqueous
      sample as donor phase through a thin phase of organic solvent (n-dodecane)
      filling the pores of the hollow fiber wall and then back extracted into the
      organic acceptor phase (methanol) located in the lumen of the hollow fiber. All
      variables affecting the extraction of analyte including acceptor organic solvent
      type, concentration of NaOH in donor phase, ionic strength of the sample and
      extraction time were studied. The linear range was 20-1000 and 5-250 ng/mL for
      plasma and urine, respectively (r(2)>=0.990). The limits of detection were
      calculated to be 7.2 and 1.6 ng/mL for plasma and urine, respectively. The
      relative standard deviation was lower than 8.2% for both urine and plasma
      samples. The enrichment factors were between 45 and 54. The method was
      successfully applied for the analysis of amantadine in urine and plasma samples.

PMID- 21956022
TI  - Rapid independent trait evolution despite a strong pleiotropic genetic
      correlation.
AB  - Genetic correlations are the most commonly studied of all potential constraints
      on adaptive evolution. We present a comprehensive test of constraints caused by
      genetic correlation, comparing empirical results to predictions from theory. The
      additive genetic correlation between the filament and the corolla tube in wild
      radish flowers is very high in magnitude, is estimated with good precision (0.85
      +/- 0.06), and is caused by pleiotropy. Thus, evolutionary changes in the
      relative lengths of these two traits should be constrained. Still, artificial
      selection produced rapid evolution of these traits in opposite directions, so
      that in one replicate relative to controls, the difference between them increased
      by six standard deviations in only nine generations. This would result in a 54%
      increase in relative fitness on the basis of a previous estimate of natural
      selection in this population, and it would produce the phenotypes found in the
      most extreme species in the family Brassicaceae in less than 100 generations.
      These responses were within theoretical expectations and were much slower than if
      the genetic correlation was zero; thus, there was evidence for constraint. These
      results, coupled with comparable results from other species, show that evolution
      can be rapid despite the constraints caused by genetic correlations.

PMID- 21956023
TI  - Conditional heteroscedasticity as a leading indicator of ecological regime
      shifts.
AB  - Regime shifts are massive, often irreversible, rearrangements of nonlinear
      ecological processes that occur when systems pass critical transition points.
      Ecological regime shifts sometimes have severe consequences for human well-being,
      including eutrophication in lakes, desertification, and species extinctions.
      Theoretical and laboratory evidence suggests that statistical anomalies may be
      detectable leading indicators of regime shifts in ecological time series, making
      it possible to foresee and potentially avert incipient regime shifts. Conditional
      heteroscedasticity is persistent variance characteristic of time series with
      clustered volatility. Here, we analyze conditional heteroscedasticity as a
      potential leading indicator of regime shifts in ecological time series. We
      evaluate conditional heteroscedasticity by using ecological models with and
      without four types of critical transition. On approaching transition points, all
      time series contain significant conditional heteroscedasticity. This signal is
      detected hundreds of time steps in advance of the regime shift. Time series
      without regime shifts do not have significant conditional heteroscedasticity.
      Because probability values are easily associated with tests for conditional
      heteroscedasticity, detection of false positives in time series without regime
      shifts is minimized. This property reduces the need for a reference system to
      compare with the perturbed system.

PMID- 21956024
TI  - Consumer effects on the vital rates of their resource can determine the outcome
      of competition between consumers.
AB  - Current competition theory does not adequately address the fact that competitors
      may affect the survival, growth, and reproductive rates of their resources.
      Ecologically important interactions in which consumers affect resource vital
      rates range from parasitism and herbivory to mutualism. We present a general
      model of competition that explicitly includes consumer-dependent resource vital
      rates. We build on the classic MacArthur model of competition for multiple
      resources, allowing direct comparison with expectations from established concepts
      of resource-use overlap. Consumers share a stage-structured resource population
      but may use the different stages to different extents, as they do the different
      independent resources in the classic model. Here, however, the stages are
      dynamically linked via consumer-dependent vital rates. We show that consumers'
      effects on resource vital rates result in two important departures from classic
      results. First, consumers can coexist despite identical use of resource stages,
      provided each competitor shifts the resource stage distribution toward stages
      that benefit other species. Second, consumers specializing on different resource
      stages can compete strongly, possibly resulting in competitive exclusion despite
      a lack of resource stage-use overlap. Our model framework demonstrates the
      critical role that consumer-dependent resource vital rates can play in
      competitive dynamics in a wide range of biological systems.

PMID- 21956025
TI  - Seed supply, recruitment, and assembly: quantifying relative seed and
      establishment limitation in a plant community context.
AB  - There is a growing consensus that the relative constraints of seed limitation and
      establishment limitation in recruitment strongly influence abundance patterns in
      plant communities. Although these constraints have direct relevance to
      coexistence, most investigations utilize a seed addition approach that offers
      limited insight into these dynamics. Here we report the results of an assembly
      experiment with annual plant species from California grasslands to examine how
      propagule pool characteristics (dominant species abundance, functional diversity)
      influence establishment and seed limitation (density independence and density
      dependence across a gradient of seed supply) for each species, as well as how
      these constraints affect community diversity. Species were predominantly
      colimited by seed and establishment constraints, exhibiting saturating
      recruitment functions with increased seed supply. Consistent with competition
      colonization trade-off predictions, recruitment constraints often depended on the
      degree of seed limitation of the competitive dominant, Brassica nigra; diversity
      was greatest in communities where Brassica was seed limited. Functional
      similarity within the propagule pool did not affect recruitment across a range of
      seed supply; likewise, functional diversity of the propagule pool was not related
      to community diversity. We conclude that seed limitation of the dominant species
      rather than niche similarity influences interspecific competition for safe sites
      and scales up to affect community-level diversity.

PMID- 21956026
TI  - Deciphering information encoded in birdsong: male songbirds with fertile mates
      respond most strongly to complex, low-amplitude songs used in courtship.
AB  - Research on the function of acoustic signals has focused on high-amplitude long
      range songs (LRS) and largely ignored low-amplitude songs produced by many
      species during close-proximity, conspecific interactions. Low-amplitude songs can
      be structurally identical to LRS (soft LRS), or they can be widely divergent,
      sharing few spectral and temporal attributes with LRS (short-range song [SRS]).
      SRS is often more complex than LRS and is frequently sung by males during
      courtship. To assess function, we performed two playback experiments on males of
      a socially monogamous songbird. We compared responses of males whose mates were
      fertile or nonfertile with differences in song structure (SRS vs. LRS and soft
      LRS), amplitude (SRS and soft LRS vs. LRS), and tempo (slow SRS vs. fast SRS).
      Males responded more strongly to SRS than to LRS or soft LRS, indicating that
      song structure had a greater effect on response than song amplitude. SRS tempo
      did not detectably affect male response. Importantly, males responded more
      strongly to SRS when their mates were fertile, presumably because hearing SRS can
      indicate that a male's mate is being courted by an intruding male and a strong
      response can deter extrapair competitors. We conclude that low-amplitude songs
      can function in both inter- and intrasexual communication and should receive
      greater attention in future studies of mate choice and male-male competition.

PMID- 21956027
TI  - Predation and the evolutionary dynamics of species ranges.
AB  - Gene flow that hampers local adaptation can constrain species distributions and
      slow invasions. Predation as an ecological factor mainly limits prey species
      ranges, but a richer array of possibilities arises once one accounts for how
      predation alters the interplay of gene flow and selection. We extend previous
      single-species theory on the interplay of demography, gene flow, and selection by
      investigating how predation modifies the coupled demographic-evolutionary
      dynamics of the range and habitat use of prey. We consider a model for two
      discrete patches and a complementary model for species along continuous
      environmental gradients. We show that predation can strongly influence the
      evolutionary stability of prey habitat specialization and range limits. Predators
      can permit prey to expand in habitat or geographical range or, conversely, cause
      range collapses. Transient increases in predation can induce shifts in prey
      ranges that persist even if the predator itself later becomes extinct. Whether a
      predator tightens or loosens evolutionary constraints on the invasion speed and
      ultimate size of a prey range depends on the predator effectiveness, its mobility
      relative to its prey, and the prey's intraspecific density dependence, as well as
      the magnitude of environmental heterogeneity. Our results potentially provide a
      novel explanation for lags and reversals in invasions.

PMID- 21956028
TI  - Adaptive dynamics of competition for nutritionally complementary resources:
      character convergence, displacement, and parallelism.
AB  - Consumers acquire essential nutrients by ingesting the tissues of resource
      species. When these tissues contain essential nutrients in a suboptimal ratio,
      consumers may benefit from ingesting a mixture of nutritionally complementary
      resource species. We investigate the joint ecological and evolutionary
      consequences of competition for complementary resources, using an adaptive
      dynamics model of two consumers and two resources that differ in their relative
      content of two essential nutrients. In the absence of competition, a
      nutritionally balanced diet rarely maximizes fitness because of the dynamic
      feedbacks between uptake rate and resource density, whereas in sympatry,
      nutritionally balanced diets maximize fitness because competing consumers with
      different nutritional requirements tend to equalize the relative abundances of
      the two resources. Adaptation from allopatric to sympatric fitness optima can
      generate character convergence, divergence, and parallel shifts, depending not on
      the degree of diet overlap but on the match between resource nutrient content and
      consumer nutrient requirements. Contrary to previous verbal arguments that
      suggest that character convergence leads to neutral stability, coadaptation of
      competing consumers always leads to stable coexistence. Furthermore, we show that
      incorporating costs of consuming or excreting excess nonlimiting nutrients
      selects for nutritionally balanced diets and so promotes character convergence.
      This article demonstrates that resource-use overlap has little bearing on
      coexistence when resources are nutritionally complementary, and it highlights the
      importance of using mathematical models to infer the stability of ecoevolutionary
      dynamics.

PMID- 21956029
TI  - On the maintenance of sex chromosome polymorphism by sex-antagonistic selection.
AB  - Complex sex determination systems are a priori unstable and require specific
      selective forces for their maintenance. Analytical derivations suggest that sex
      antagonistic selection may play such a role, but this assumes absence of
      recombination between the sex-determining and sex-antagonistic genes. Using
      individual-based simulations and focusing on the sex chromosome and coloration
      polymorphisms of platy fishes as a case study, we show that the conditions for
      polymorphism maintenance induce female biases in primary sex ratios, so that sex
      ratio selection makes the system collapse toward male or female heterogamety as
      soon as recombinant genotypes appear. However, a polymorphism can still be
      maintained under scenarios comprising strong sexual selection against dull males,
      mild natural selection against bright females, and low recombination rates.
      Though such conditions are plausibly met in natural populations of fishes
      harboring such polymorphisms, quantitative empirical evaluations are required to
      properly test whether sex antagonistic selection is a causal agent or whether
      other selective processes are required (such as local mate competition favoring
      female-biased sex ratios).

PMID- 21956030
TI  - Population and life-history consequences of within-cohort individual variation.
AB  - The consequences of within-cohort (i.e., among-individual) variation for
      population dynamics are poorly understood, in particular for the case where life
      history is density dependent. We develop a physiologically structured population
      model that incorporates individual variation among and within cohorts and allows
      us to explore the intertwined relationship between individual life history and
      population dynamics. Our model is parameterized for the lizard Zootoca vivipara
      and reproduces well the species' dynamics and life history. We explore two common
      mechanisms that generate within-cohort variation: variability in food intake and
      variability in birth date. Predicted population dynamics are inherently very
      stable and do not qualitatively change when either of these sources of individual
      variation is introduced. However, increased within-cohort variation in food
      intake leads to changes in morphology, with longer but skinnier individuals, even
      though mean food intake does not change. Morphological changes result from a
      seemingly universal nonlinear relationship between growth and resource
      availability but may become apparent only in environments with strongly
      fluctuating resources. Overall, our results highlight the importance of using a
      mechanistic framework to gain insights into how different sources of
      intraspecific variability translate into life-history and population-dynamic
      changes.

PMID- 21956031
TI  - A quantitative test of population genetics using spatiogenetic patterns in
      bacterial colonies.
AB  - It is widely accepted that population-genetics theory is the cornerstone of
      evolutionary analyses. Empirical tests of the theory, however, are challenging
      because of the complex relationships between space, dispersal, and evolution.
      Critically, we lack quantitative validation of the spatial models of population
      genetics. Here we combine analytics, on- and off-lattice simulations, and
      experiments with bacteria to perform quantitative tests of the theory. We study
      two bacterial species, the gut microbe Escherichia coli and the opportunistic
      pathogen Pseudomonas aeruginosa, and show that spatiogenetic patterns in colony
      biofilms of both species are accurately described by an extension of the one
      dimensional stepping-stone model. We use one empirical measure, genetic diversity
      at the colony periphery, to parameterize our models and show that we can then
      accurately predict another key variable: the degree of short-range cell migration
      along an edge. Moreover, the model allows us to estimate other key parameters,
      including effective population size (density) at the expansion frontier. While
      our experimental system is a simplification of natural microbial community, we
      argue that it constitutes proof of principle that the spatial models of
      population genetics can quantitatively capture organismal evolution.

PMID- 21956032
TI  - Condensation onto the skin as a means for water gain by tree frogs in tropical
      Australia.
AB  - Green tree frogs, Litoria caerulea, in the wet-dry tropics of northern Australia
      remain active during the dry season with apparently no available water and
      temperatures that approach their lower critical temperature. We hypothesized that
      this surprising activity might be because frogs that are cooled during nighttime
      activity gain water from condensation by returning to a warm, humid tree hollow.
      We measured the mass gained when a cool frog moved into either a natural or an
      artificial hollow. In both hollows, water condensed on cool L. caerulea,
      resulting in water gains of up to 0.93% of body mass. We estimated that the water
      gained was more than the water that would be lost to evaporation during activity.
      The use of condensation as a means for water gain may be a significant source of
      water uptake for species like L. caerulea that occur in areas where free water is
      unavailable over extended periods.

PMID- 21956035
TI  - Coexistence and coevolution in fluctuating environments: can the storage effect
      evolve?
AB  - Both theoretical and empirical work have shown that the temporal storage effect
      can promote coexistence. However, the storage effect depends on temporally
      fluctuating demographic rates, such as interannually variable germination rates.
      Because variable demographic rates often reduce fitness, we asked how a storage
      effect might evolve. Using a model of competing annual plants, we find that
      variable germination (and hence a storage effect) can evolve only if germination
      is positively correlated with high-fecundity years (predictive germination) or if
      one species has limited ability to evolve. Outside of these conditions, the
      storage effect is evolutionarily unstable: if two species were thrown together
      with traits that would permit a storage effect, they would coevolve constant
      germination rates and the storage effect would vanish. Our results suggest that
      for the temporal storage effect to be widespread, either germination must
      commonly be positively correlated with later growth or fecundity or community
      assembly must reflect biogeographic processes more than they do coevolution.

PMID- 21956036
TI  - Resonance of plankton communities with temperature fluctuations.
AB  - The interplay between intrinsic population dynamics and environmental variation
      is still poorly understood. It is known, however, that even mild environmental
      noise may induce large fluctuations in population abundances. This is due to a
      resonance effect that occurs in communities on the edge of stability. Here, we
      use a simple predator-prey model to explore the sensitivity of plankton
      communities to stochastic environmental fluctuations. Our results show that the
      magnitude of resonance depends on the timescale of intrinsic population dynamics
      relative to the characteristic timescale of the environmental fluctuations.
      Predator-prey communities with an intrinsic tendency to oscillate at a period T
      are particularly responsive to red noise characterized by a timescale of tau =
      T/2pi. We compare these theoretical predictions with the timescales of
      temperature fluctuations measured in lakes and oceans. This reveals that plankton
      communities will be highly sensitive to natural temperature fluctuations. More
      specifically, we demonstrate that the relatively fast temperature fluctuations in
      shallow lakes fall largely within the range to which rotifers and cladocerans are
      most sensitive, while marine copepods and krill will tend to resonate more
      strongly with the slower temperature variability of the open ocean.

PMID- 21956038
TI  - Paced left ventricular QRS width and ECG parameters predict outcomes after
      cardiac resynchronization therapy: PROSPECT-ECG substudy.
AB  - BACKGROUND: For patients with symptomatic New York Heart Association class III or
      IV, ejection fraction <= 35%, and QRS >= 130 ms, cardiac resynchronization
      therapy (CRT) has become an established treatment option. However, use of these
      implant criteria fails to result in clinical or echocardiographic improvement in
      30% to 45% of CRT patients. METHODS AND RESULTS: The Predictors of Response to
      CRT (PROSPECT)-ECG is a substudy of the prospective observational PROSPECT trial.
      ECGs collected before, during, and after CRT implantation were analyzed. Primary
      outcomes were improvement in clinical composite score (CCS) and reduction of left
      ventricular end systolic volume (LVESV) of >15% after 6 months. Age, sex, cause
      of cardiomyopathy, myocardial infarction location, right ventricular function,
      mitral regurgitation, preimplantation QRS width, preimplantation PR interval,
      preimplantation right ventricular-paced QRS width, preimplantation axis
      categories, LV-paced QRS width, postimplantation axis categories, difference
      between biventricular (Bi-V) pacing and preimplantation QRS width, and QRS bundle
      branch morphological features were analyzed univariably in logistic regression
      models to predict outcomes. All significant predictors (alpha=0.1), age, and sex
      were used for multivariable analyses. Cardiomyopathy cause interaction and
      subanalyses were also performed. In multivariable analyses, only QRS left bundle
      branch morphological features predicted both CCS (odds ratio [OR]=2.46, P=0.02)
      and LVESV (OR=2.89, P=0.048) response. The difference between Bi-V and
      preimplantation QRS width predicted CCS improvement (OR=0.89, P=0.04). LV-paced
      QRS width predicted LVESV reduction (OR=0.86, P=0.01). Specifically, an LV-paced
      QRS width of <= 200 ms was predictive of nonischemic LVESV reduction (OR=5.12,
      P=0.01). CONCLUSIONS: Baseline left bundle branch QRS morphological features, LV
      paced QRS width, and the difference between Bi-V and preimplantation QRS width
      can predict positive outcomes after CRT and may represent a novel intraprocedural
      method to optimize coronary sinus lead placement. CLINICAL TRIAL REGISTRATION:
      URL: http://www.clinicaltrials.gov. Unique identifier: NCT00253357.

PMID- 21956039
TI  - Genotype- and mutation site-specific QT adaptation during exercise, recovery, and
      postural changes in children with long-QT syndrome.
AB  - BACKGROUND: Exercise stress testing has shown diagnostic utility in adult
      patients with long-QT syndrome (LQTS); however, the QT interval adaptation in
      response to exercise in pediatric patients with LQTS has received little
      attention. METHODS AND RESULTS: One-hundred fifty-eight patients were divided
      into 3 groups: Those with LQTS type 1 (LQT1) or LQTS type 2 (LQT2) and normal
      control subjects without cardiovascular disease. Each patient underwent a uniform
      exercise protocol with a cycle ergometer followed by a 9-minute recovery phase
      with continuous 12-lead ECG monitoring. Each patient underwent a baseline ECG
      while resting in the supine position and in a standstill position during
      continuous ECG recording to determine changes in the QT and RR intervals. Fifty
      patients were gene-positive for LQTS (n=29 for LQT1 and n=21 for LQT2), and the
      control group consisted of 108 patients. QT interval adaptation was abnormal in
      the LQT1 patients compared with LQT2 and control patients (P<0.001). A corrected
      QT interval (QTc) >460 ms in the late recovery phase at 7 minutes predicted LQT1
      or LQT2 versus control subjects with 96% specificity, 86% sensitivity, and a 91%
      positive predictive value. A recovery DeltaQTc((7 min-1 min)) >30 ms predicted
      LQT2 versus LQT1 with 75% sensitivity, 82% specificity, and a 75% positive
      predictive value. The postural DeltaQT was significantly different between LQTS
      and control groups (P=0.005). CONCLUSIONS: Genotype-specific changes in
      repolarization response to exercise and recovery exist in the pediatric
      population and are of diagnostic utility in LQTS. An extended recovery phase is
      preferable to assess the repolarization response after exercise in the pediatric
      population.

PMID- 21956040
TI  - The pterygopalatine ganglion and its role in various pain syndromes: from anatomy
      to clinical practice.
AB  - The postsynaptic fibers of the pterygopalatine or sphenopalatine ganglion (PPG or
      SPG) supply the lacrimal and nasal glands. The PPG appears to play an important
      role in various pain syndromes including headaches, trigeminal and sphenopalatine
      neuralgia, atypical facial pain, muscle pain, vasomotor rhinitis, eye disorders,
      and herpes infection. Clinical trials have shown that these pain disorders can be
      managed effectively with sphenopalatine ganglion blockade (SPGB). In addition,
      regional anesthesia of the distribution area of the SPG sensory fibers for nasal
      and dental surgery can be provided by SPGB via a transnasal, transoral, or
      lateral infratemporal approach. To arouse the interest of the modern-day
      clinicians in the use of the SPGB, the advantages, disadvantages, and
      modifications of the available methods for blockade are discussed.?

PMID- 21956041
TI  - Implications of gene copy-number variation in health and diseases.
AB  - Inter-individual genomic variations have recently become evident with advances in
      sequencing techniques and genome-wide array comparative genomic hybridization.
      Among such variations single nucleotide polymorphisms (SNPs) are widely studied
      and better defined because of availability of large-scale detection platforms.
      However, insertion-deletions, inversions, copy-number variations (CNVs) also
      populate our genomes. The large structural variations (>3 Mb) have been known for
      past 20 years, however, their link to health and disease remain ill-defined. CNVs
      are defined as the segment of DNA >1 kb in size, and compared with reference
      genome vary in its copy number. All these types of genomic variations are bound
      to have vital role in disease susceptibility and drug response. In this review,
      the discussion is confined to CNVs and their link to health, diseases and drug
      response. There are several CNVs reported till date, which have important roles
      in an individual's susceptibility to several complex and common disorders. This
      review compiles some of these CNVs and analyzes their involvement in diseases in
      different populations, analyses available evidence and rationalizes their
      involvement in the development of disease phenotype. Combined with SNP,
      additional genomic variations including CNV, will provide better correlations
      between individual genomic variations and health.

PMID- 21956042
TI  - Neonatal desflurane exposure induces more robust neuroapoptosis than do
      isoflurane and sevoflurane and impairs working memory.
AB  - BACKGROUND: In animal models, neonatal exposure to volatile anesthetics induces
      neuroapoptosis, leading to memory deficits in adulthood. However, effects of
      neonatal exposure to desflurane are largely unknown. METHODS: Six-day-old C57BL/6
      mice were exposed to equivalent doses of desflurane, sevoflurane, or isoflurane
      for 3 or 6 h. Minimum alveolar concentration was determined by the tail-clamp
      method as a function of anesthesia duration. Apoptosis was evaluated by
      immunohistochemical staining for activated caspase-3, and by TUNEL. Western blot
      analysis for cleaved poly-(adenosine diphosphate-ribose) polymerase was performed
      to examine apoptosis comparatively. The open-field, elevated plus-maze, Y-maze,
      and fear conditioning tests were performed to evaluate general activity, anxiety
      related behavior, working memory, and long-term memory, respectively. RESULTS:
      Minimum alveolar concentrations at 1 h were determined to be 11.5% for
      desflurane, 3.8% for sevoflurane, and 2.7% for isoflurane in 6-day-old mice.
      Neonatal exposure to desflurane (8%) induced neuroapoptosis with an anatomic
      pattern similar to that of sevoflurane or isoflurane; however, desflurane induced
      significantly greater levels of neuroapoptosis than almost equivalent doses of
      sevoflurane (3%) or isoflurane (2%). In adulthood, mice treated with these
      anesthetics had impaired long-term memory, whereas no significant anomalies were
      detected in the open-field and the elevated plus-maze tests. Although performance
      in a working memory task was normal in mice exposed neonatally to sevoflurane or
      isoflurane, mice exposed to desflurane had significantly impaired working memory.
      CONCLUSIONS: In an animal model, neonatal desflurane exposure induced more
      neuroapoptosis than did sevoflurane or isoflurane and impaired working memory,
      suggesting that desflurane is more neurotoxic than sevoflurane or isoflurane.

PMID- 21956043
TI  - Self-stigma and its relationship with insight, demoralization, and clinical
      outcome among people with schizophrenia spectrum disorders.
AB  - BACKGROUND: Paradoxically, insight is associated with positive outcomes, such as
      better treatment adherence and recovery, and negative outcomes, such as
      depression, hopelessness, low self-esteem, and quality of life. Self-stigma as a
      moderating variable can be decisive whether more insight leads to better or worse
      outcome. On the other hand, self-stigma can act as a mediator between insight and
      outcomes. We therefore examined self-stigma both as a moderator and a mediator.
      METHODS: Insight, self-stigma, demoralization, symptoms, and functioning were
      assessed among 145 outpatients with schizophrenia spectrum disorders using
      questionnaires and structured interviews. Structural equation modeling was used
      to analyze the cross-sectional data. RESULTS: Results confirmed self-stigma as a
      moderator: The association of insight and demoralization was stronger as self
      stigma increased. Self-stigma also partially mediated the positive relationship
      between insight and demoralization. Moreover, demoralization fully mediated the
      adverse associations of self-stigma with psychotic symptoms and global
      functioning. DISCUSSION: Given the decisive role of self-stigma regarding the
      detrimental consequences of insight, interventions should address self-stigma,
      particularly if psychoeducational or other interventions have increased insight.
      Therapeutic implications for changes of dysfunctional beliefs related to illness
      and self and change of self-concept in the context of recovery at the level of
      narrative identity are discussed.

PMID- 21956044
TI  - Utilizing pre-therapy clinical schema and initial CT changes to predict
      progression-free survival in patients with metastatic renal cell carcinoma on
      VEGF-targeted therapy: a preliminary analysis.
AB  - OBJECTIVE: Because of varying treatment effectiveness with vascular endothelial
      growth factor (VEGF)-targeted therapy in patients with metastatic renal cell
      carcinoma (RCC), the association of prognostic pre-therapy clinical schema,
      initial post-therapy computed tomography (CT) findings, and combination thereof
      in predicting progression-free survival (PFS) was investigated. A predictive
      biomarker that combines clinical risk factors and CT imaging features associated
      with initial response to therapy would be useful in stratifying patients into
      risk groups to guide therapy, in designing and interpreting results of clinical
      trials, in planning risk-directed therapy, and in patient counseling. Early
      identification of poor responders using an imaging biomarker may reduce drug
      related toxicity and cost and allow for a therapeutic intervention before disease
      burden significantly advances. MATERIALS AND METHODS: For this institutional
      review board-approved HIPAA-compliant retrospective study, baseline data for 82
      patients with metastatic RCC treated with sunitinib or sorafenib was obtained for
      risk stratification by Memorial Sloan Kettering Cancer Center (MSKCC) criteria
      and criteria by Heng et al. (J Clin Oncol 2009;27:5794-9), (described here as
      "VEGF prognostic factors criteria"). The initial post-therapy CT was evaluated by
      Response Assessment Criteria in Solid Tumors (RECIST), Choi criteria, and
      Morphology, Attenuation, Size, and Structure (MASS) criteria. Kaplan-Meier
      estimates of PFS (the reference standard) for each patient group and overall
      accuracy of each method and combined criteria were calculated. RESULTS: The MSKCC
      model, VEGF prognostic factors criteria, RECIST, MASS criteria, MSKCC + MASS
      criteria, and VEGF prognostic factors + MASS criteria each demonstrated
      significant differences in PFS among patient groups (P < 0.005 for each, Log-rank
      test). Stratification of patient groups by Choi criteria was not statistically
      significant with respect to PFS (P = 0.101). MSKCC + MASS criteria yielded the
      highest overall accuracy for identifying PFS >= 1 year (77%) and for identifying
      PFS < 1 year (77%). CONCLUSIONS: A combination of pre-therapy clinical risk
      factors and CT imaging response by MASS criteria more effectively predicted PFS
      in patients with metastatic RCC on VEGF-targeted therapy than any single method.

PMID- 21956045
TI  - Is Memorial Sloan-Kettering Cancer Center risk classification appropriate for
      Japanese patients with metastatic renal cell carcinoma in the cytokine era?
AB  - OBJECTIVES: We investigated the prognosis of Japanese patients with metastatic
      renal cell carcinoma (RCC), and analyzed the validity of Memorial Sloan-Kettering
      Cancer Center (MSKCC) risk classification. MATERIALS AND METHODS: The endpoint of
      the present study was overall survival. Relationships between overall survival
      and potential prognostic factors were assessed using the Cox proportional hazard
      model with a step-wise procedure. Prognostic assessment was also performed
      according to the MSKCC risk classification. The predictive accuracy of the MSKCC
      risk classification was measured employing the concordance index. RESULTS: The
      median survival for all patients was 22 months (95% CI, 19-28 months). The eight
      factors were identified as independent prognostic factor; time from initial
      diagnosis to metastasis, low hemoglobin (Hb), lactate dehydrogenase (LDH),
      corrected serum calcium (cCa), C-reactive protein (CRP), and the presence or
      absence of liver metastasis, bone metastasis, and lymph node metastasis. When the
      MSKCC risk classification was applied to patients, the median overall survival
      was not reached and 26 and 10 months in the patients classified as favorable,
      intermediate, and poor risk, respectively. The c-index was 0.73. CONCLUSIONS: The
      prognosis of Japanese metastatic renal cell carcinoma patients may be better than
      that of previous studies from North America or Europe. Although there are some
      differences in the rate of patients in the risk groups and survival time by risk
      group between these patients, the MSKCC risk classification may be applicable for
      Japanese patients with metastatic renal cell carcinoma.

PMID- 21956046
TI  - Explaining primary healthcare pharmacy expenditure using classification of
      medications for chronic conditions.
AB  - BACKGROUND: The Valencian Autonomous Community (Spain) has implemented a scheme
      of purchasing services with the participation of public and private providers.
      Five districts are managed using public-private partnership. The financing model
      is capitation and inter-center invoice. The pharmaceutical benefits are not
      included in the per capita assignment. OBJECTIVES: Modeling and explaining
      pharmacy expenditure using electronic prescriptions drug data. METHODS: A
      database of electronic prescription corresponding to 625,246 patients between
      November 2008 and October 2009 was used to run four linear models that explain
      the pharmaceutical expenditures. We take as dependent variable the neperian log
      of total pharmacy annual cost per patient in the primary health setting. The
      independent variables used combined demographics with revised classification in
      18 chronic conditions obtained from the anatomical therapeutic chemical
      classification index (ATC). RESULTS: The retrospective model selected included:
      gender, pharmaceutical co-payment status and 8 dummy variables for the number of
      chronic conditions of each patient from 1 to 8 or more. The goodness-of-fit
      achieved is measured in R(2) of 57%. CONCLUSIONS: These models must be considered
      in the current capitation system for pharmaceutical budgeting in a primary care
      setting established at regional level, as is the case in the Valencian Autonomous
      Community. The use of diagnostics and information regarding hospital encounters
      appears to be a complementary option for refining models of capitation of
      pharmaceutical and total health expenditure.

PMID- 21956047
TI  - Can patient injury claims be utilised as a quality indicator?
AB  - OBJECTIVES: To examine the association between patient injury claims and well
      known quality indicators and to assess whether claims can be utilised in
      performance measurement. METHODS: Data were derived from administrative registers
      and comprised hip and knee replacement patients (n=34181) in Finland from 1998 to
      2003. Hospital-level correlations were calculated between claims and quality
      indicators (5-year revision rate, 1-year deep infection rate, and 14-day
      readmission rate), while logistic regression analysis was used to analyze patient
      level data for an association between claims and quality indicators. RESULTS:
      Correlations between claims and revisions as well as claims and infections were
      statistically significant, with correlation coefficients ranging from 0.21 to
      0.62. In the regression analysis, both the revision and the infection indicator
      had a positive and statistically significant association with filing a claim (OR
      1.002; 95% CI 1.001-1.003 and 1.001; 1.00005-1.001, respectively) and obtaining
      compensation (1.003; 1.001-1.005 and 1.001; 1.0003-1.002, respectively).
      CONCLUSIONS: A claims indicator has the potential to be applied as a quality
      indicator. It should be complemented, however, with other indicators or actions
      to improve its acceptability by health professionals and to mitigate its possible
      undesirable effects.

PMID- 21956048
TI  - National public health policy in a local context--implementation in two Swedish
      municipalities.
AB  - OBJECTIVES: In 2003 the wide-ranging Swedish National Public Health Policy
      (SNPHP), with a focus on health determinants, was adopted by the Swedish
      parliament. In the context of multilevel governance, SNPHP implementation is
      dependent on self-governed municipalities and counties. The aim of the study is,
      from a municipal perspective, to investigate public-health policies in two
      municipalities. METHODS: Content analysis of documents and interviews provided a
      foundation for an explorative case study. RESULTS: The SNPHP at national level is
      overriding but politically controversial. At local level, a health-determinants
      perspective was detectable in the policies implemented, but none regarding to
      health equality. At local level, the SNPHP is not regarded as implementable;
      rather, limited parts have, to varying degrees, been reconciled with local public
      health goals, according to municipal needs and conditions. A success-promoting
      factor in the two municipalities was the presence of committed and knowledgeable
      actors/implementers. Also, the municipality with a more centrally controlled and
      stable party-political leadership succeeded better in implementing structural and
      intersectoral community-wide policies for coordinated local health promotion.
      CONCLUSIONS: The contents of national and local public-health policies differ,
      and municipalities that have implemented their own local health policies do not
      seem to regard the SNPHP as justifiable or adoptable. If the SNPHP overall aim
      regarding equal health is to be achieved homogeneously in Swedish municipalities,
      its contents and purpose need clearer management and negotiation, so that
      implementation of the national policy locally is understandable and motivated.

PMID- 21956050
TI  - Avascular necrosis of the femoral head in children with acute lymphoblastic
      leukemia: a 4- to 9-year follow-up study.
AB  - Avascular necrosis of the femoral head is usually seen in children aged 1.5 to 10
      years, reaching a peak incidence between the ages of 4 and 9. Avascular necrosis
      of the femoral head is a known complication of corticosteroid therapy in acute
      lymphoblastic leukemia. There are few reports in the literature regarding the
      natural history of this condition, and there is no consensus on its management.
      This study examined the natural history of avascular necrosis of the femoral head
      in children with leukemia. From 1993 to 2006, a total of 865 children with acute
      lymphoblastic leukemia were admitted to the hematology-oncology ward of a
      children's hospital. The diagnosis of acute lymphoblastic leukemia was
      established by bone marrow aspiration. Based on clinical and radiographic
      findings, avascular necrosis of the femoral head was found in 7 patients; these
      patients underwent follow-up for 4 to 9 years. Avascular necrosis of the femoral
      head was clinically symptomatic in all of the children, and they had advanced
      radiographic collapse of the femoral head. However, the head of the femur was not
      at risk in any patient based on clinical and radiographic findings. Patients
      received supportive treatment such as abduction brace and physiotherapy. After 4
      to 9 years of follow-up, clinical and radiographic results were satisfactory.
      Provided that the head of the femur is not at risk, avascular necrosis of the
      femoral head in children with acute lymphoblastic leukemia may be successfully
      managed with nonoperative care.

PMID- 21956049
TI  - Long-term results of arthroscopic labral debridement: predictors of outcomes.
AB  - Limited data exist regarding the long-term results of labral debridement and the
      effect of coexisting pathology on outcomes. Our hypothesis was that untreated
      coexisting hip pathologies such as femoroacetabular impingement and arthritis
      significantly affect the outcomes of arthroscopic labral debridement. Between
      1996 and 2003, fifty consecutive patients who underwent hip arthroscopy and
      labral debridement with a mean follow-up of 8.4 years were included in our study.
      Patients' preoperative Harris Hip Scores and coexisting pathologies such as
      femoroacetabular impingement, dysplasia, or arthritis were recorded as variables.
      Postoperative Harris Hip Score and satisfaction at final follow-up were recorded
      as outcomes. Good or excellent results were achieved in 62% of cases (58% in
      patients with untreated femoroacetabular impingement and 19% in patients with
      arthritis). Failures included 2 cases that were converted to total hip
      replacement (4.5 and 5.2 years after index procedure) due to advancement of
      arthritis and 1 case of repeat arthroscopy for cam decompression. Patients with
      no coexisting pathology had significantly higher satisfaction and Harris Hip
      Scores. Almost all of the patients with low postoperative Harris Hip Scores had
      arthritic changes. Arthritis had a significant correlation with low postoperative
      Harris Hip Scores and satisfaction. Coexisting pathology, especially arthritis
      and untreated femoroacetabular impingement, can result in inferior outcomes.
      Arthroscopic labral debridement of symptomatic tears in selected patients with no
      coexisting pathology can result in favorable long-term results. Arthritis is the
      strongest independent predictor of poor outcomes.

PMID- 21956051
TI  - Cost-effectiveness of teaching hospitals for the operative management of hip
      fractures.
AB  - Hospitals with lower costs are not necessarily superior to those that are more
      expensive, because the more costly institutions might offer better outcomes. The
      purpose of this study was to consider prices and outcomes in an integrated model
      and thereby determine if teaching hospitals are cost-effective for the care of
      hip fractures. We analyzed the claims data of a sample of 18,908 Medicare
      patients who were admitted to one of 190 acute care hospitals for surgical
      treatment of a hip fracture. For each hospital, we assessed the relationship
      between the total per capita Medicare payments over a 6-month period following
      admission and the 30-day and 6-month mortality. The data were analyzed as a
      function of hospital type: teaching vs nonteaching. The mean adjusted costs were
      $5910 per patient higher at teaching hospitals compared to nonteaching hospitals
      (approximately $24,000 vs $18,000) However, the adjusted 6-month mortality was
      1.4% lower at major teaching hospitals. The adjusted incremental cost
      effectiveness for teaching hospitals was $422,143 per life saved. By that
      measure, each life saved would have to yield nearly 8.5 additional quality
      adjusted life years (QALY) to attain the $50,000/QALY standard thought to
      represent cost-effective spending, an unlikely target given the age of the
      typical hip fracture patient. Nonetheless, because teaching hospitals are more
      expensive than non-teaching hospitals, a relatively small cut in the overall cost
      of care at teaching hospitals could dramatically decrease the marginal cost of
      each life saved. The elements of teaching hospital care that improve survival
      might be identified in further studies and instituted, perhaps, at non-teaching
      hospitals without greatly increasing their cost structure.

PMID- 21956052
TI  - Sagittal plane deformity during femoral lengthening.
AB  - The purpose of this study was to determine the incidence and degree of sagittal
      plane deformity that occurs during limb lengthening of the femur. Twenty-one
      patients (25 limbs) were identified who underwent femoral lengthening. The limbs
      were lengthened a mean of 6.1 cm, and mean follow-up was 1.5 years. The immediate
      postoperative deformity in the sagittal plane was 8.3 degrees ; this deformity
      did not progress during lengthening (P<.05). Mean displacement in the sagittal
      plane was 3.1 mm.Angular deformities, although typically small, can occur in the
      sagittal plane and may be accompanied by displacement. These deformities are
      usually present immediately postoperatively and typically do not worsen
      significantly with lengthening.

PMID- 21956053
TI  - Use of positron emission tomography to detect infection around antibiotic-loaded
      cement spacers in patients with high C-reactive protein levels.
AB  - In patients who have antibiotic-loaded cement hip spacers in the interim period,
      the correct diagnosis of infection eradication is the major determinant before
      reimplantation arthroplasty. Diagnosis is usually based on clinical findings and
      serum C-reactive protein (CRP) levels. However, diagnosis can be challenging when
      the clinical findings are normal but the CRP level is high. From March 2007 to
      January 2008, fluorodeoxy-glucose positron emission tomography (FDG-PET) was used
      to detect infection around antibiotic-loaded cement spacers in 13 patients (mean
      age, 60 years). Although patients' clinical conditions were deemed suitable for
      reimplantation, their serum CRP levels were persistently elevated (mean, 54 mg/L)
      an average of 120 days (range, 28-413 days) after the first-stage operation.
      Reimplantation total hip arthroplasty (THA) was subsequently performed in 7
      patients based on the negative findings of FDG-PET. In 6 patients, FDG-PET was
      positive for infection. The persistence of infection was confirmed in 3 of these
      patients by another debridement surgery. Staged reimplantation THA was delayed in
      1 patient who underwent repeat debridement and in 3 patients who were treated
      with extended periods of oral antibiotics. Of the 11 staged reimplantation THAs,
      only 1 reinfection was noted at an average follow-up of 48 months. The success
      rate of 91% suggests FDG-PET could help in the differential diagnosis of
      infection around cement spacers, especially in patients with normal clinical
      findings but elevated CRP levels.

PMID- 21956054
TI  - Influence of the position of the fibular head after implantation of a total knee
      prosthesis on femorotibial rotation.
AB  - A gold standard for the correct rotation of the tibial component has not been
      established in total knee arthroplasty (TKA). The target parameter of correct
      rotation is the facilitation of femorotibial rotation over the entire range of
      motion with no implant overhang. Although the origin of the lateral collateral
      ligament is a recognized landmark for determining the rotation of the femoral
      component (epicondylar axis), the attachment of the lateral collateral ligament
      has not been taken into consideration for adjusting tibial rotation until now.
      The objective of the current investigation was to examine whether the position of
      the fibular head, as the attachment of the lateral collateral ligament,
      influences femorotibial rotation. Seventy patients who underwent TKA were
      enrolled in this retrospective study. Computed tomography (CT) of the operated
      knee was performed 6 months postoperatively in all cases and the position of the
      lateral facet of the fibular head and the tibial tuberosity, and the geometric
      center of the tibia and the femoral epicondyles were determined. The angle
      between the lateral facet of the fibular head, the geometric center of the tibia,
      and the tibial tuberosity was 45.7 degrees +/-6.9 degrees . The angle between the
      surgical epicondylar axis and the line from tibial tuberosity to tibial center
      was 69 degrees +/-8.3 degrees . This close correlation (R=.73; P<.001) shows that
      the position of the fibular head determines femorotibial rotation. The fibular
      head may become a helpful landmark for establishing the rotation of the tibial
      component; it could be useful in interpretation of postoperative CT scans in
      knees suspected of tibial malrotation.

PMID- 21956055
TI  - Radiographic results of an accelerometer-based, handheld surgical navigation
      system for the tibial resection in total knee arthroplasty.
AB  - In total knee arthroplasty (TKA), intramedullary and extramedullary tibial
      alignment guides are not proven to be highly accurate in obtaining alignment
      perpendicular to the mechanical axis in the coronal plane. The objective of this
      study was to determine the accuracy of an accelerometer-based, handheld surgical
      navigation system in obtaining a postoperative tibial component alignment within
      2 degrees  of the intraoperative goal in both the coronal and sagittal planes. A
      total of 151 TKAs were performed by 2 surgeons using a handheld surgical
      navigation system to perform the tibial resection. Postoperatively, standing
      anteroposterior hip-to-ankle radiographs and lateral knee-to-ankle radiographs
      were performed to determine the varus/valgus alignment and the posterior slope of
      the tibial components relative to the mechanical axis in both the coronal and
      sagittal planes. Findings showed that 95.3% of the tibial components were placed
      within 2 degrees  of the intraoperative goal in the coronal plane and 96.1% of
      the components were placed within 2 degrees  of the intraoperative goal in the
      sagittal plane. Overall, mean postoperative lower-extremity alignment was -0.3
      degrees +/-2.1 degrees , with 97% of patients having an alignment within 3
      degrees  of a neutral mechanical axis. The handheld surgical navigation system
      improves the accuracy of the tibial resection and subsequent tibial component
      alignment in TKA. It is able to combine the accuracy of computer-assisted surgery
      systems with the ease of use and familiarity of conventional, extramedullary
      alignment systems, and the ability to adjust both the coronal and sagittal
      alignments intraoperatively may prove clinically useful in TKA.

PMID- 21956056
TI  - Limb alignment after open-wedge high tibial osteotomy and its effect on the
      clinical outcome.
AB  - The purpose of this study was to evaluate the accuracy of alignment after open
      wedge high tibial osteotomy and its effect on the clinical outcome. A prospective
      case series of 56 consecutive patients underwent open-wedge high tibial osteotomy
      fixed with a TomoFix plate fixator (Synthes, West Chester, Pennsylvania). The
      correction angle was radiologically determined preoperatively and at 6 months
      postoperatively. The patients were clinically and radiologically examined
      preoperatively and at 3, 6, and 36 months postoperatively. The mechanical axis of
      50 knees was corrected from an average of 5.7 degrees  varus to 1.3 degrees 
      valgus. Forty-three patients had an acceptable correction with Mikulicz line
      crossing the tibial plateau between 50% to 70% of the tibial plateau width
      measured from the medial border. Undercorrection (<50%, group II) and over
      correction (>70%, group III) were found in 4 and 3 patients, respectively. The
      mean Lysholm-Gillquist score at 36 months had improved in all groups, with a
      statistically lower value for group II. Open-wedge high tibial osteotomy results
      in significant improvement of symptoms and function in all patients in the short
      term, even with under- and overcorrection of the osteotomy. Undercorrection was
      associated with a significantly lower clinical outcome in comparison to the
      accurate correction and overcorrection. Ligamentous laxity or soft tissue
      slackness of the knee can influence the overall correction after high tibial
      osteotomy and must be considered in preoperative planning. Patients with a high
      body mass index had inferior clinical results after open-wedge high tibial
      osteotomy.

PMID- 21956057
TI  - Functional outcomes for surgically treated 3- and 4-part proximal humerus
      fractures.
AB  - Surgical treatment of 3- and 4-part proximal humeral fractures remains
      challenging. This study retrospectively evaluated functional outcomes of locked
      plate fixation vs hemi-arthroplasty in 57 patients with 3- and 4-part proximal
      humerus fractures from 2003 to 2005 with a mean follow-up time of 35 months
      (range, 15.7-52.7 months). Mean patient age was 56.9 years (range, 29-81.7 years)
      for the open reduction and internal fixation group (n=42) and 66.4 years (range,
      38.1-90 years) for hemiarthroplasty group (n=15). All 57 patients completed the
      American Shoulder and Elbow Surgeons score, the Simple Shoulder Test, the Euroqol
      EQ-5D, [corrected] and the visual analog pain scale. Range of motion, the
      Constant Score, and the UCLA Shoulder score were used to evaluate a subset of 33
      patients. Forty-one patients in the open reduction and internal fixation group
      achieved union, and 1 had symptomatic avascular necrosis requiring subsequent
      hemiarthroplasty. Two patients had implant removal for impingement symptoms. In
      the hemiarthroplasty group, there was 1 revision for a loose prosthesis. The
      American Shoulder and Elbow Surgeons score (P=.023), Simple Shoulder Test
      (P=.012), patient satisfaction (P=.034), Constant Score (P=.008), Kelsh Adjusted
      Constant Score (P=.015), UCLA Shoulder score (P=.01), and range of motion
      (forward flexion, P=.002; abduction, P=.001) were significantly better in the
      open reduction and internal fixation group than the hemiarthroplasty group. No
      significant differences between the groups existed in terms of SF-12 (physical,
      P=.118; mental, P=.134), Euroqol EQ-5D [corrected] (P=.169), or visual analog
      pain scale scores (P=.135), but all trended toward better with open reduction and
      internal fixation.

PMID- 21956058
TI  - Calcaneal reconstruction for the late complication of calcaneus fracture.
AB  - Calcaneal fracture is the most common fracture in the tarsal bones. Treatment is
      difficult because the patterns of fracture are various and complications occur
      frequently. The purpose of this study was to evaluate the clinical results of
      calcaneal reconstruction for chronic complications after calcaneal fracture. rom
      September 2001 to November 2004, calcaneal reconstruction was performed in 24
      patients (25 feet). We reviewed 21 patients (22 feet) who could be followed up >2
      years postoperatively. Patients who underwent subtalar arthrodesis and simple
      bone resection were excluded. Patients who underwent calcaneal sliding osteotomy
      were included. Nineteen men and 2 women ranged in age from 27 to 54 years (mean,
      44.4 years). The mean interval between the first operation and reconstructive
      operation was 11.2 months (range, 3-31 months). The mean follow-up period after
      calcaneal reconstruction was 29.8 months (range, 24-38 months). Bohler angle,
      calcaneal pitch, and talocalcaneal height were checked pre- and postoperatively.
      The most common patient report was pain on the inferior aspect of the lateral
      malleolus (16 patients) and calcaneal tuberosity (3 patients). All the mean
      values of talocalcaneal height, calcaneal pitch, and Bohler angle improved, which
      was statistically significant. In the postoperative period, 10 patients were very
      satisfied, 9 were satisfied, and 3 were not satisfied. Although pain did not
      completely resolve, all patients were satisfied postoperatively.

PMID- 21956059
TI  - Ultrasonography as a diagnostic tool in assessing deltoid ligament injury in
      supination external rotation fractures of the ankle.
AB  - The medial deltoid ligament is the primary stabilizing structure in the ankle
      joint following lateral malleolar fracture. However, medial deltoid ligament
      ruptures are difficult to diagnose using current imaging modalities. We
      hypothesized that ultrasonography can be used to accurately allow early clinical
      assessment of ankle fracture stability, thereby negating the need to perform
      plain film stress views of the acutely injured ankle. This prospective study
      included 12 patients (age range, 18-72) with supination external rotation
      fractures requiring operative fixation. Following induction of anesthesia,
      ultrasonography examination was performed, followed by an arthrogram under
      fluoroscopic screening. Radiographs, ultrasonography, and arthrographic findings
      were compared. There was 100% correlation between ultrasonography and arthrogram
      findings. Ultrasonography accurately diagnosed medial deltoid rupture with a
      sensitivity of 100% and specificity of 100%. Plain film radiographs of the ankle
      had a sensitivity of 57.1% and a specificity of 60%. The difference between these
      was significant (chi(2)=.0091). This study demonstrates diagnostic
      ultrasonography to be an accurate diagnostic modality in assessing medial deltoid
      ligament integrity in patients with supination external rotation fractures. It
      offers the same sensitivity and specificity as arthrography without the need for
      additional invasive procedures. Its relative ease of use and lack of ionizing
      radiation make it a potentially useful tool, particularly in a busy trauma
      service.

PMID- 21956060
TI  - Retrospective comparison of H-graft and posterior vertebral graft procedures for
      the treatment of thoracolumbar burst fractures.
AB  - A retrospective cohort study was conducted to compare fusion rates achieved by H
      grafts, posterior vertebral grafts, and no graft for the surgical treatment of
      thoracolumbar fractures. Ninety-two patients were included in this study. The
      patients fell into 1 of 3 groups: those who received H-grafts (n=36), posterior
      vertebral grafts (n=30), and no graft (n=26). Mean follow-up was 38 months
      (range, 24-51 months). All operations were performed by a single senior surgeon.
      All patients underwent operative treatment with posterior reduction and
      instrumentation. Radiographic parameters, estimated blood loss, operative time,
      and length of hospital stay were compared among patients in the 3 graft groups.
      Differences were assessed using unpaired t tests. P values <.05 were considered
      significant. We found no significant difference among groups in age, fracture
      location, or type of fracture. Patients who received H-grafts or posterior
      vertebral grafts achieved solid fusion, but spontaneous fusion occurred in only 2
      patients who received no bone graft. Most patients with neurological deficits
      showed significant neurological improvement. Operative time and estimated blood
      loss were significantly lower in the no-graft group than in the H-graft and
      posterior vertebral graft groups (P<.05). Mean loss of correction, operative
      time, and estimated blood loss were lower for patients who received H-grafts than
      for those who received posterior vertebral grafts (P<.05). The use of an atlas
      fixation system in combination with a posterior H-graft for the treatment of
      thoracolumbar fracture is a stable and reliable method that effectively prevents
      inner fixation failure and reduces bone loss and anisotropy.

PMID- 21956061
TI  - Systematic review and meta-analysis of randomized controlled trials: comparison
      of total disk replacement with anterior cervical decompression and fusion.
AB  - The authors performed a systematic review and meta-analysis to evaluate whether
      there is a beneficial clinical effect of total disk replacement compared with
      anterior cervical diskectomy and fusion for the treatment of single-level
      symptomatic cervical disk disease. A comprehensive literature search of multiple
      databases, including PubMed (1966-2011), Cochrane Controlled Trials Register
      (CENTRAL; issue 1, 2011), and Embase (1984-2011), was conducted to identify
      studies that met the inclusion criteria. Methodologic quality was assessed and
      relevant data were retrieved, and if appropriate, meta-analysis was performed.
      Eight randomized controlled trials were identified; six of the 8 reported 24
      month follow-up results. At 24 months, total disk replacement was demonstrated to
      be more beneficial for patients compared with anterior cervical diskectomy and
      fusion for the following outcomes: overall success rate (odds ratio [OR], 1.79;
      95% confidence interval [CI], 1.37-2.33; P<.0001), overall reoperation rate
      (OR,.36; CI, .21-.61; P=0), reoperation rate for revision (OR, .12; CI, .02 to
      .64; P=.01), and visual analog scale neck pain scores (standard mean differences
      [SMD], -.48; CI, -.91 to -.05; P=.03). Other outcomes, including Neck Disability
      Index scores (SMD, -.02; CI, -.44 to .27; P=.67) and visual analog scale arm pain
      scores (SMD, -.21; CI, -.63 to .22; P=.34), demonstrated no differences between
      the 2 groups. For patients with single-level symptomatic cervical disk disease,
      total disk replacement was found to be more effective than anterior cervical
      diskectomy and fusion in the 2 outcomes of overall success rate and overall
      reoperation rate at 24 months. Long-term results also showed total disk
      replacement trended to be more effective than anterior cervical diskectomy and
      fusion in some aspects.

PMID- 21956062
TI  - Use of a rugby helmet brace for postoperative treatment of muscular torticollis.
AB  - Prior to 1992, our postoperative management for congenital muscular torticollis
      consisted of either plaster cast immobilization or no immobilization, depending
      on the patient's age and the degree of contracture. However, some patients
      required further surgery and developed complications. In 1992, we produced rugby
      helmet braces for postoperative management. The purpose of this study was to
      compare the clinical results of the previous postoperative management with the
      results achieved using rugby helmet braces. Twenty-five children aged younger
      than 6 years underwent caudal partial resection of the sternocleidomastoid
      muscle. Twelve children aged 6 years and older underwent cranial tenotomy. These
      37 patients were divided into 2 groups: no immobilization or plaster
      immobilization (group A; n=19) and rugby helmet braces (group B; n=18). Canale's
      method was used for evaluation of clinical results. In group A, the results were
      good in 12 patients, fair in 4, and poor in 3, whereas all 18 patients in group B
      had good results. Two patients in group A required further surgery, and
      complications were observed in 5 patients. In group B, alopecia areata was
      observed in 1 patient.The rugby helmet brace is easy to put on and remove,
      providing good retention and allowing for physiotherapy. It provides a useful
      method of postoperative management for congenital muscular torticollis.

PMID- 21956063
TI  - Preferred use of polyhexanide in orthopedic surgery.
AB  - In orthopedic and trauma surgery, the most frequently used antiseptic is
      polyhexanide. Its favored application is based on prepossessing tissue
      compatibility in contrast to various antiseptics and a high antimicrobiological
      effect. Recent studies showed toxic effects of this antiseptic on human
      chondrocytes. The aim of this study was to further analyze the toxic and
      apoptotic effects of polyhexanide on primary human chondrocytes. The hypothesis
      of this study was that polyhexanide induces apoptosis on human chondrocytes.
      Primary human chondrocytes were isolated and cultured from human donors with
      osteoarthritis of the knee who underwent total arthroplasty and had no indication
      of infection. Polyhexanide at a standard concentration of 0.04% was added to the
      monolayer cultures. Early and late apoptotic cells were analyzed by flow
      cytometric detection of annexin V, active caspases, and 7AAD, and by fluorescence
      microscopy using annexin V and propidium iodide staining. Flow cytometric
      analysis demonstrated an increase of annexin V and active caspases expression of
      human chondrocytes after incubation with polyhexanide. Fluorescence microscopy
      demonstrated a high number of annexin V positive and propidium iodide negative
      early apoptotic cells. The data show that polyhexanide promotes apoptosis on
      primary human chondrocytes in vitro, which may indicate the use of polyhexanide
      in septic joint surgery.

PMID- 21956064
TI  - What opportunities are available for resident involvement in national orthopedic
      and subspecialty societies?
AB  - As physician involvement in health policy grows, there will be an increasing need
      for future leaders in orthopedics. Interested orthopedic residents may be unaware
      of opportunities for leadership involvement in professional and subspecialty
      organizations. This article investigates whether national and subspecialty
      organizations offer membership to residents, allow residents to participate in
      committees, and provide opportunities for scholarly activity and mentorship. The
      authors surveyed 20 national orthopedic professional and subspecialty societies
      to evaluate the availability and cost of resident membership, meeting attendance
      and participation, research funding, committee membership, and mentorship
      opportunities. Each society's Web site was reviewed, and societies were contacted
      by phone if further inquiry was needed. Of the 20 orthopedic societies surveyed,
      11 allowed resident membership. Five of 20 societies allowed residents to serve
      on committees, with a total of 14 total positions for residents. Four
      organizations provided formalized mentorship programs to residents. Although
      opportunities for resident involvement in subspecialty and professional societies
      are available in the majority of groups surveyed, the Orthopaedic Trauma
      Association and American Society for Surgery of the Hand provided the most
      comprehensive collection of opportunities. Residents should also pursue
      involvement in other organizations that may be more readily accessible, such as
      local, state, and regional orthopedic and medical societies. Increased resident
      participation in these organizations may help in increasing the 14 nationally
      available committee positions for orthopedic residents. Our orthopedic profession
      and societies should encourage motivated residents to pursue involvement and
      leadership at the national level.

PMID- 21956065
TI  - Contralateral deep venous thrombosis after hip arthroscopy.
AB  - Since the 1980s, hip arthroscopy has become an accepted treatment modality for a
      variety of hip conditions. It is generally considered a low-risk procedure with a
      low rate of complications. The risk of developing a deep venous thrombosis (DVT)
      or venous thromboembolism following these procedures is also thought to be low,
      and most patients undergoing these procedures receive no pharmacologic
      prophylaxis postoperatively. This article presents a case of a 33-year-old woman
      with a history of oral contraceptive use who presented 13 days after a routine
      hip arthroscopy with pain and swelling in the contralateral thigh.
      Ultrasonography revealed acute DVTs in the left common femoral, superficial
      femoral, and popliteal veins. She was admitted to the hospital and treated
      accordingly. A workup for thrombophilic disorders was negative. We believe that
      her history of oral contraceptive use, the use of axial traction, and asymmetric
      forces about the pelvis during the procedure contributed to this postoperative
      complication. Although this complication is rare and the use of pharmacologic
      prophylaxis is not common, physicians must be aware of this potential
      complication following hip arthroscopy.

PMID- 21956066
TI  - Noninflammatory pseudotumor simulating venous thrombosis after metal-on-metal hip
      resurfacing.
AB  - Metal-on-metal hip resurfacing has become a widespread procedure, especially in
      young, physically active patients. Pseudotumor is a new complication that can
      occur after hip resurfacing and metal-on-metal total hip arthroplasty (THA). This
      article presents a case of a 37-year-old woman who underwent metal-on-metal
      resurfacing of the left hip for symptomatic osteoarthritis. Twelve months
      following implantation, the patient reported painless swelling of the left lower
      leg. There was no clinical evidence of a deep venous thrombosis. Ultrasound and
      computed tomography showed a solid cystic lesion in the iliopsoas muscle, which
      communicated with the hip joint and compressed the external iliac vein. As a
      consequence, the cystic lesion was resected marginally. A few months later, the
      patient reported some discomfort in the groin and symptoms of instability,
      metallic clicking, and a restricted range of motion. Clinical and radiological
      examination revealed normal findings. Determining the serum concentration of
      cobalt and chromium revealed high increased levels of these metal ions. Ten
      months following excision of the pseudotumor, the patient reported recurrent
      swelling of the left lower leg. Computed tomography of the affected area showed a
      lobulated cystic formation; therefore, a relapse was suspected. At the second
      revision, the mass was excised and the implant was revised to a conventional
      ceramic-on-ceramic THA. At 30-month follow-up, the patient was doing well and
      there were no signs of local recurrence. Additionally, the metal ion levels of
      cobalt and chromium in the blood had significantly decreased.

PMID- 21956067
TI  - Fracture of a titanium sleeve-encased third-generation ceramic liner in a modern
      THA.
AB  - Due to their excellent tribology, ceramics are increasingly used for total hip
      arthroplasty (THA) in young patients. Fracture rates for contemporary ceramics
      range from 0% to 0.004%. Recently, ceramic liners are encased in a titanium
      sleeve to further decrease the chances of fracture. We encountered 1 case of a
      metal-encased acetabular liner fracture in a ceramic-on-ceramic articulation in a
      series of 764 hips. Our literature review revealed no reports of metal-encased
      ceramic liner fracture. A 60-year-old woman presented 27 months after a bilateral
      ceramic-on-ceramic THA. She reported mechanical grinding and clicking from the
      left hip on extension. There was no history of trauma or fall. Examination
      revealed a nonantalgic gait and audible-palpable crepitations on the left hip.
      Range of motion of the left hip was intact with no subluxation. Radiographs
      revealed fractured ceramic insert and an excessively anteverted socket on the
      left side. Intraoperative findings revealed gross impingement in the form of
      indentation of the metal femoral neck against the elevated metal rim encasing the
      liner. Revision THA was performed using an uncemented polyethylene liner while
      retaining the well-fixed cup and stem. The Harris Hip Score at 4.5-year follow-up
      was 100, with no evidence of osteolysis or polyethylene wear.

PMID- 21956068
TI  - New method to remove a broken guide pin in the hip joint.
AB  - Removing a broken guide wire is difficult and challenging. This article reports a
      method that was used to successfully remove a broken guide wire in 3 patients who
      underwent operative treatment for intertrochanteric fractures of the femur. Under
      general anesthesia, the first patient was placed on the orthopedic fracture
      table, and closed reduction of the hip fracture was performed under the image
      intensifier. A 2-mm non-threaded pin was used in the center of the femoral neck,
      and the amount of reaming required was determined. The reaming proceeded without
      any difficulty until the reamer failed to progress, which was attributed to the
      presence of a sclerotic or calcar region. Under fluoroscopy, on an
      anteroposterior view, the pin was parallel with the reamer; however, the authors
      failed to check the lateral image. After reaming through the hard tissue, the
      reamer suddenly passed through easily. On checking under the scope, it was noted
      that the pin was broken. The tip of the pin passed the acetabulum but did not
      enter the pelvis. Efforts to remove the broken pin failed. An attempt to reach
      the pin using a dynamic hip screw reamer also failed. Ultimately, the broken pin
      was removed using a 2-mm cannulated drill bit under fluoroscopy. After the
      experience with the first patient, in the other 2 cases, the authors used a
      cannulated drill bit to avoid any extensive reaming and trauma to the tissues.
      With this method, the authors were able to remove the broken pin easily in a few
      minutes.

PMID- 21956069
TI  - Bilateral fatigue fracture of the femoral components in a cruciate-retaining
      cementless total knee prosthesis.
AB  - This article reports a case of bilateral fatigue fracture of the femoral
      components in a cruciate-retaining uncemented total knee arthroplasty (TKA). A 75
      year-old woman (height, 158 cm; weight, 72 kg; body mass index, 29.2) had
      undergone one-stage bilateral TKA for osteoarthritis 11 years previously at the
      author's institution. Surgery was performed using an uncemented Flexible Nichidai
      Knee. Equal tension of the collateral ligaments and normal mechanical axis were
      achieved during the primary procedure. The patient was an ardent lover of the
      game of badminton and had higher activity levels with daily playing. At 8 years
      postoperatively, she started complaining of mild pain in both knees. The pain
      gradually increased, and at 11 years postoperatively, she had difficulty walking.
      Anteroposterior radiographs showed narrowing of the medial joint space,
      indicating wear of the polyethylene insert. Lateral radiographs showed signs of
      broken implants in both knees. There were no signs of gross implant loosening or
      osteolysis. One-stage revision surgery was performed, and the knees were
      converted to cemented posterior-stabilized TKAs. At revision, the bilateral
      femoral components were found to be fractured at the junction between the
      trochlear flange and the medial condyle, anteriorly to the medial peg. The
      polyethylene insert showed mild wear at the medial middle portion. In the
      majority of case reports, stress fractures of the femoral component have
      predominantly affected the medial condyle, following uncemented implantation of
      fixed-bearing knees. In this case, failure of bone ingrowth in uncemented
      components, higher body mass index, and a higher athletic activity led to fatigue
      fracture of the femoral components.

PMID- 21956070
TI  - Clavicle fracture with thoracic penetration and hemopneumothorax but without
      neurovascular compromise.
AB  - Clavicle fractures are rarely associated with more severe neurologic or vascular
      injuries. When these associated injuries are encountered, prompt recognition and
      treatment are paramount to optimize outcome. The majority of fractures that
      result in neurovascular compromise are from high-energy trauma; however, a high
      index of suspicion should be present in all cases as low-energy trauma can also
      result in more catastrophic injury. This article describes a case of a low-energy
      clavicle fracture in a 28-year-old woman that resulted in intrathoracic
      penetration of the fracture fragment with hemopneumothorax. The patient underwent
      successful chest tube placement and open reduction and internal fixation of the
      fracture. A multidisciplinary team was used during surgery, including
      cardiothoracic, trauma, and orthopedic surgery. Two years postoperatively, the
      patient was back to normal activities with no neurologic, pulmonary, or vascular
      sequelae. This case highlights the importance of a comprehensive physical
      examination and inspection of all radiographs so that associated injuries are not
      missed.

PMID- 21956071
TI  - Stress fractures of the lateral rays in the cavovarus foot: indication for
      surgical intervention.
AB  - Lateral ray stress fractures are a known complication of the cavovarus foot
      deformity. Malpositioning of the forefoot and hindfoot leads to increased
      pressure on the heel and lateral rays, resulting in significant morbidity.
      Patients with nonprogressive deformities can be managed surgically or
      nonsurgically in an attempt to decrease adverse events. It is often difficult to
      predict which patients will benefit most from a surgical intervention. This
      article describes 2 model cases of stress fractures in patients with
      nonprogressive cavovarus foot deformities. Patient 1 was an active patient with a
      minor, flexible cavovarus deformity, and patient 2 was a relatively inactive
      patient with a severe, fixed deformity. These cases serve to illustrate a
      spectrum of the 2 major risk factors for the development of a stress fracture of
      the lateral rays: severity of deformity and activity level of the patient. We
      believe the relationship between these 2 risk factors constitutes a threshold
      that allows the development of a stress fracture to serve as an adequate marker
      for surgical intervention. Within this patient population, a stress fracture
      indicates that given a patient's lifestyle, his or her deformity is sufficient
      enough to cause significant and repeated morbidity. Surgical restoration of the
      foot to plantigrade will eliminate the increased forces to the lateral
      metatarsals and decrease the incidence of further injury. Thus, stress fractures
      of the lateral rays in patients with nonprogressive cavovarus deformities should
      be considered an indication for surgical intervention.

PMID- 21956072
TI  - Functioning paraganglioma of the cervical spine.
AB  - Extradural paraganglioma of the cervical spine is rarely seen. Few reports of
      this functioning disorder appear in the literature. A 29-year-old woman presented
      with a 1-year history of left shoulder pain and occasional transitional
      dizziness. This is the first case of a functioning cervical spinal paraganglioma
      with symptoms of catecholamine excess throughout the operation. A mass in the
      neck region was discovered by the patient 2 months prior to hospital admission.
      Physical examination revealed an egg-shaped soft and unflexible mass with no
      clear boundary in the anterior left part of the neck. Neither sensory disturbance
      nor motor weakness was evident in the upper and lower extremities. Laboratory
      studies were normal. Both computed tomography and magnetic resonance imaging
      implied neurilemmoma. Embolization of the branches supplying the mass was taken
      to reduce perioperative bleeding complications 1 day preoperatively. The patient
      demonstrated frequent hypertensive spikes with tumor handling. The blood pressure
      changed between 80/40 mm Hg and 200/105 mm Hg throughout the surgery. The tumor
      was dissected successfully from the paraspinal tissues, followed by spinal cord
      decompression of C4 to C6, C5 corpectomy, anterior column reconstruction, and
      anterior internal fixation with a plate. The histopathological examination
      yielded a postoperative diagnosis of paraganglioma. Diagnosis and treatment of
      this rare case require comprehensive perioperative management and meticulous
      surgical excision.

PMID- 21956073
TI  - A practical review of perineural versus intraneural injections:  a call for
      standard nomenclature.

PMID- 21956074
TI  - Regional anesthesia for ambulatory surgery:  where ultrasound has made a
      difference.

PMID- 21956075
TI  - Opinion/Editorial and review of recent literature: Where ultrasound has yet to
      make a difference in regional anesthesia.

PMID- 21956076
TI  - Ultrasound basics for the busy novice practitioner.

PMID- 21956077
TI  - The 5 most common ultrasound artifacts encountered during ultrasound-guided
      regional anesthesia.

PMID- 21956078
TI  - Practical concepts in the monitoring of injection pressures during peripheral
      nerve blocks.

PMID- 21956079
TI  - Practical concepts in nerve stimulation:  impedance and other recent advances.

PMID- 21956080
TI  - Update on the use of lipid emulsions in local anesthetic systemic toxicity: a
      focus on differential efficacy and lipid emulsion as part of advanced cardiac
      life support.

PMID- 21956082
TI  - Multimodal systemic and intra-articular analgesics.

PMID- 21956081
TI  - Additives to local anesthetics for peripheral nerve blockade.

PMID- 21956083
TI  - Postoperative nausea and vomiting in ambulatory regional anesthesia.

PMID- 21956084
TI  - Regional anesthesia in patients with preexisting neuropathy.

PMID- 21956085
TI  - Thromboprophylaxis and regional anesthesia in the ambulatory setting.

PMID- 21956087
TI  - Preface--Regional anesthesia for ambulatory surgery 2011-2012 (when the sequel
      leads to a trilogy...).

PMID- 21956089
TI  - Ecological and evolutionary limits to species geographic ranges.

PMID- 21956088
TI  - The androgen receptor and stem cell pathways in prostate and bladder cancers
      (review).
AB  - Bladder cancer is three times more common in men than in women. However, the
      physiological basis of the male predominance of bladder cancer remains poorly
      understood. A higher than expected association of prostate and bladder cancers
      has also been reported which may indicate a common mechanism of carcinogenesis.
      Consistent with this, androgens and the androgen receptor (AR) play essential
      roles in prostate carcinogenesis and are believed to play a role in bladder
      carcinogenesis. There is also evidence implicating cancer stem cells in prostate
      and bladder cancers. Indeed putative prostate and bladder cancer stem cells share
      some common molecular features. We highlight key proteins (CD49f, CD133, PTEN,
      CD44) which are implicated in both prostate and bladder cancers and are enriched
      in putative prostate and bladder cancer stem cells. We examine published
      chromatin immuno-precipitation studies analyzing the genome-wide distribution of
      the AR to identify AR association with, and by inference potential AR-regulation
      of, these loci. We discuss recent evidence indicating a role for the AR in the
      splicing of the key urological stem cell protein CD44. We propose a model whereby
      aberrant AR regulation of these putative stem cell proteins contributes to
      malignant transformation of prostate and bladder cells. For these reasons we
      propose that the relationship between androgens and cancer stem cell associated
      proteins warrants further investigation.

PMID- 21956090
TI  - The geography of demography: long-term demographic studies and species
      distribution models reveal a species border limited by adaptation.
AB  - Potential causes of species' geographic distribution limits fall into two broad
      classes: (1) limited adaptation across spatially variable environments and (2)
      limited opportunities to colonize unoccupied areas. Combining demographic
      studies, analyses of demographic responses to environmental variation, and
      species distribution models, we investigated the causes of range limits in a
      model system, the eastern border of the California annual plant Clarkia xantiana
      ssp. xantiana. Vital rates of 20 populations varied with growing season
      temperature and precipitation: fruit number and overwinter survival of 1-year-old
      seeds declined steeply, while current-year seed germination increased modestly
      along west-to-east gradients in decreasing temperature, decreasing mean
      precipitation, and increasing variation in precipitation. Long-term stochastic
      finite rate of increase, lambda(s), exhibited a fourfold range and varied among
      geologic surface materials as well as with temperature and precipitation. Growth
      rate declined significantly toward the eastern border, falling below 1 in three
      of the five easternmost populations. Distribution models employing
      demographically important environmental variables predicted low habitat
      favorability beyond the eastern border. Models that filtered or weighted
      population presences by lambda(s) predicted steeper eastward declines in
      favorability and assigned greater roles in setting the distribution to among-year
      variation in precipitation and to geologic surface material. These analyses
      reveal a species border likely set by limited adaptation to declining
      environmental quality.

PMID- 21956091
TI  - Population genetics and the evolution of geographic range limits in an annual
      plant.
AB  - Abstract  Theoretical models of species' geographic range limits have identified
      both demographic and evolutionary mechanisms that prevent range expansion. Stable
      range limits have been paradoxical for evolutionary biologists because they
      represent locations where populations chronically fail to respond to selection.
      Distinguishing among the proposed causes of species' range limits requires
      insight into both current and historical population dynamics. The tools of
      molecular population genetics provide a window into the stability of range
      limits, historical demography, and rates of gene flow. Here we evaluate
      alternative range limit models using a multilocus data set based on DNA sequences
      and microsatellites along with field demographic data from the annual plant
      Clarkia xantiana ssp. xantiana. Our data suggest that central and peripheral
      populations have very large historical and current effective population sizes and
      that there is little evidence for population size changes or bottlenecks
      associated with colonization in peripheral populations. Whereas range limit
      populations appear to have been stable, central populations exhibit a signature
      of population expansion and have contributed asymmetrically to the genetic
      diversity of peripheral populations via migration. Overall, our results discount
      strictly demographic models of range limits and more strongly support
      evolutionary genetic models of range limits, where adaptation is prevented by a
      lack of genetic variation or maladaptive gene flow.

PMID- 21956092
TI  - Theoretical perspectives on the statics and dynamics of species' borders in
      patchy environments.
AB  - Understanding range limits is a fundamental problem in ecology and evolutionary
      biology. In 1963, Mayr argued that "contaminating" gene flow from central
      populations constrained adaptation in marginal populations, preventing range
      expansion, while in 1984, Bradshaw suggested that absence of genetic variation
      prevented species from occurring everywhere. Understanding stability of range
      boundaries requires unraveling the interplay of demography, gene flow, and
      evolution of populations in concrete landscape settings. We walk through a set of
      interrelated spatial scenarios that illustrate interesting complexities of this
      interplay. To motivate our individual-based model results, we consider a
      hypothetical zooplankter in a landscape of discrete water bodies coupled by
      dispersal. We examine how patterns of dispersal influence adaptation in sink
      habitats where conditions are outside the species' niche. The likelihood of
      observing niche evolution (and thus range expansion) over any given timescale
      depends on (1) the degree of initial maladaptation; (2) pattern (pulsed vs.
      continuous, uni- vs. bidirectional), timing (juvenile vs. adult), and rate of
      dispersal (and hence population size); (3) mutation rate; (4) sexuality; and (5)
      the degree of heterogeneity in the occupied range. We also show how the genetic
      architecture of polygenic adaptation is influenced by the interplay of selection
      and dispersal in heterogeneous landscapes.

PMID- 21956093
TI  - Quantifying the impact of gene flow on phenotype-environment mismatch: a
      demonstration with the scarlet monkeyflower Mimulus cardinalis.
AB  - Geographic range margins offer testing grounds for limits to adaptation. If range
      limits are concordant with niche limits, range expansions require the evolution
      of new phenotypes that can maintain populations beyond current range margins.
      However, many species' range margins appear static over time, suggesting limits
      on the ability of marginal populations to evolve appropriate phenotypes. A
      potential explanation is the swamping gene flow hypothesis, which posits that
      asymmetrical gene flow from large, well-adapted central populations prevents
      marginal populations from locally adapting. We present an empirical framework for
      combining gene flow, environment, and fitness-related phenotypes to infer the
      potential for maladaptation, and we demonstrate its application using the scarlet
      monkeyflower Mimulus cardinalis. We grew individuals sampled from populations on
      a latitudinal transect under varied temperatures and determined the phenotypic
      deviation (PD), the mismatch between phenotype and local environment. We inferred
      gene flow among populations and predicted that populations receiving the most
      temperature- or latitude-weighted immigration would show the greatest PD and that
      these populations were likely marginal. We found asymmetrical gene flow from
      central to marginal populations. Populations with more latitude-weighted
      immigration had significantly greater PD but were not necessarily marginal. Gene
      flow may limit local adaptation in this species, but swamping gene flow is
      unlikely to explain its northern range limit.

PMID- 21956094
TI  - Thermal tolerance in widespread and tropical Drosophila species: does phenotypic
      plasticity increase with latitude?
AB  - The distribution of insects can often be related to variation in their response
      to thermal extremes, which in turn may reflect differences in plastic responses
      or innate variation in resistance. Species with widespread distributions are
      expected to have evolved higher levels of plasticity than those from restricted
      tropical areas. This study compares adult thermal limits across five widespread
      species and five restricted tropical species of Drosophila from eastern Australia
      and investigates how these limits are affected by developmental acclimation and
      hardening after controlling for environmental variation and phylogeny.
      Irrespective of acclimation, cold resistance was higher in the widespread
      species. Developmental cold acclimation simulating temperate conditions extended
      cold limits by 2 degrees -4 degrees C, whereas developmental heat acclimation
      under simulated tropical conditions increased upper thermal limits by <1 degrees
      C. The response to adult heat-hardening was weak, whereas widespread species
      tended to have a larger cold-hardening response that increased cold tolerance by
      2 degrees -5 degrees C. These patterns persisted after phylogenetic correction
      and when flies were reared under high and low constant temperatures. The results
      do not support the hypothesis that widely distributed species have larger
      phenotypic plasticity for thermal tolerance limits, and Drosophila species
      distributions are therefore more closely linked to differences in innate thermal
      tolerance limits.

PMID- 21956095
TI  - Determinants of northerly range limits along the Himalayan bird diversity
      gradient.
AB  - The primary explanation for the latitudinal gradient in species diversity must
      lie in why species fail to expand ranges across different climatic regimes.
      Theories of species gradients based in niche conservatism assume that whole
      clades are confined to particular climatic regimes because the traits they share
      limit adaptation to alternative regimes. We assess these theories in an analysis
      of the twofold decline in bird species richness along the Himalayas from the
      southeast to the northwest. The presence of fewer species in the northwest is
      entirely due to a steep decline in the number of forest species; species
      occupying more open habitats show a reversed gradient. Forest species numbers are
      exceptionally high at midelevations (1,000-2,000 m) in the southeast, which
      experience a warm, wet climate not present in the northwest, and a high
      proportion of these species fail to expand their range to the northwest. Despite
      this, many species do have populations or close relatives that straddle different
      climatic regimes along altitudinal gradients and/or the regional gradient,
      implying that climate-based niche conservatism per se does not strongly constrain
      range limits. We argue that climate- and competition-mediated resource
      distributions are important in setting northerly range limits and show that one
      measure of forest resources (foliage density) is lower in the northwest.

PMID- 21956097
TI  - Sociodemographic factors associated with self-reported exercise and physical
      activity behaviors and attitudes of South Australians: results of a population
      based survey.
AB  - OBJECTIVE: To determine self-reported physical activity barriers, behaviors, and
      beliefs about exercise of a representative sample and to identify associated
      sociodemographic factors. METHOD: Face-to-face interviews conducted between
      September and December 2008, using a random stratified sampling technique.
      RESULTS: Barriers injury and illness were associated with being older, single,
      and not engaged in full-time work; lack of time was associated with being
      married, younger, female, and working full-time; and lack of motivation and cost
      were associated with being younger than 65 years. Advancing age was significantly
      associated (p < .001) with reduced physical activity. Factors including age,
      education, marital status, and area of residence were all associated with
      preferences for environment to exercise in, while all age groups (74%) felt that
      walking was the most important type of exercise for older adults. DISCUSSION: A
      better understanding of these factors may improve uptake of and adherence to
      exercise programs across the ages.

PMID- 21956096
TI  - The role of early-life socioeconomic status in breast cancer incidence and
      mortality: unraveling life course mechanisms.
AB  - OBJECTIVES: We examine (a) how breast cancer onset and survival are affected by
      various dimensions of early-life socioeconomic status (SES) and (b) the extent to
      which women's characteristics in adulthood mediate the associations between early
      life conditions and breast cancer. METHOD: We apply Cox regression models and a
      decomposition analysis to the data from the 4,275 women in the Wisconsin
      Longitudinal Study. RESULTS: Higher levels of mothers' education and early-life
      family income were associated with a greater risk of breast cancer incidence. The
      effect of mothers' education was mediated by women's adult SES and reproductive
      behaviors. Fathers' education was related negatively to breast cancer mortality,
      yet this effect was fully mediated by women's own education. DISCUSSION: This
      study identifies mechanisms linking early-life social environment to breast
      cancer onset and mortality. The findings emphasize the role of social factors in
      breast cancer incidence and survival.

PMID- 21956098
TI  - Aging and late-life depression.
AB  - OBJECTIVES: The objective of this study is to examine the relationship between
      age and depression among people aged 65 and older. METHOD: The study uses three
      waves of longitudinal data (1991, 1996, 2001) from a community and institutional
      sample of Canadians aged 65 and older. The study uses generalized linear mixed
      model techniques to estimate the trajectories of depressive symptoms and major
      depression in late life. RESULTS: There is a linear increase in depressive
      symptoms after age 65, but this occurs in the context of medical comorbidity and
      is not an independent effect of aging. There is a significant u-shaped
      relationship between age and major depression, after adjusting for selected
      covariates. DISCUSSION: The relationship between age and late-life depression is
      complex, and it depends on how the dependent variable is measured. Late-life
      depression develops through a different set of risk factors than it does in
      earlier stages of the life course. The "fourth age" appears to be a period of
      psychiatric morbidity.

PMID- 21956099
TI  - Self-reported vision impairment and its contribution to disability among older
      adults.
AB  - OBJECTIVE: To examine contributions of self-reported vision impairment to
      disability by persons 65 years and older. METHOD: We used data from the National
      Health and Nutrition Examination Survey (NHANES IV; 1999-2008; weighted N =
      6,550). The four-staged Nagi model of the disability process, incorporating
      biomarkers, disease, and physical functioning, was used as a framework to guide
      variable selection. An unadjusted ordinal logistic regression model testing
      effects of vision on daily-life activities was compared with models that
      controlled covariates associated with each stage of the disability model.
      RESULTS: Where significant effects of poor vision remained, the strongest effect
      was found for doing leisure activities at home (OR = 5.29; 95% CI [3.14, 8.90]).
      DISCUSSION: Results suggest the importance of considering multiple health factors
      when formulating comprehensive vision rehabilitation interventions.

PMID- 21956100
TI  - Social participation and maintaining recommended waist circumference: prospective
      evidence from the English Longitudinal Study of Aging.
AB  - OBJECTIVE: To investigate whether older adults participating in social activities
      are more likely to maintain or achieve recommended waist circumference (WC)
      levels. METHOD: A total of 4,280 older adults who participated in Wave 2
      (baseline) and Wave 4 (follow-up) of the English Longitudinal Study of Ageing. WC
      was measured by a nurse in both study waves. RESULTS: Participation in education,
      arts, music groups, evening classes, and in charitable associations was
      associated with maintaining recommended WC only in those men whose WC was in the
      recommended range at baseline. Participation in social activities was not
      associated with achieving recommended WC in women or men with initially large
      waist. DISCUSSION: Participation in cultural and charitable activities may help
      in maintaining a recommended level of WC in older men with WC originally in the
      recommended range.

PMID- 21956101
TI  - Mortality risk among Black and White working women: the role of perceived work
      trajectories.
AB  - OBJECTIVE: Drawing from cumulative inequality theory, the authors examine the
      relationship between perceived work trajectories and mortality risk among Black
      and White women over 36 years. METHOD: Panel data from the National Longitudinal
      Survey of Mature Women (1967-2003) are used to evaluate how objective and
      subjective elements of work shape mortality risk for Black and White women born
      between 1923 and 1937. RESULTS: Estimates from Cox proportional hazards models
      reveal that Black working women manifest higher mortality risk than White working
      women even after accounting for occupation, personal income, and household
      wealth. Perceived work trajectories were also associated with mortality risk for
      Black women but not for White women. DISCUSSION: The findings reveal the imprint
      of women's work life on mortality, especially for Black women, and illustrate the
      importance of considering personal meanings associated with objective work
      characteristics.

PMID- 21956102
TI  - Hormone replacement therapy dependent changes in breast cancer-related gene
      expression in breast tissue of healthy postmenopausal women.
AB  - Risk assessment of future breast cancer risk through exposure to sex steroids
      currently relies on clinical scorings such as mammographic density. Knowledge
      about the gene expression patterns in existing breast cancer tumors may be used
      to identify risk factors in the breast tissue of women still free of cancer. The
      differential effects of estradiol, estradiol together with gestagens, or tibolone
      on breast cancer-related gene expression in normal breast tissue samples taken
      from postmenopausal women may be used to identify gene expression profiles
      associated with a higher breast cancer risk. Breast tissue samples were taken
      from 33 healthy postmenopausal women both before and after a six month treatment
      with either 2mg micronized estradiol [E2], 2mg micronized estradiol and 1mg
      norethisterone acetate [E2+NETA], 2.5mg tibolone [T] or [no HRT]. Except for
      [E2], which was only given to women after hysterectomy, the allocation to each of
      the three groups was randomized. The expression of 102 mRNAs and 46 microRNAs
      putatively involved in breast cancer was prospectively determined in the biopsies
      of 6 women receiving [no HRT], 5 women receiving [E2], 5 women receiving
      [E2+NETA], and 6 receiving [T]. Using epithelial and endothelial markers genes,
      non-representative biopsies from 11 women were eliminated. Treatment of
      postmenopausal women with [E2+NETA] resulted in the highest number of
      differentially (p<0.05) regulated genes (16.2%) compared to baseline, followed by
      [E2] (10.1%) and [T] (4.7%). Among genes that were significantly down-regulated
      by [E2+NETA] ranked estrogen-receptor-1 (ESR1, p=0.019) and androgen receptor
      (AR, p=0.019), whereas CYP1B1, a gene encoding an estrogen-metabolizing enzyme,
      was significantly up-regulated (p=0.016). Mammary cells triggered by [E2+NETA]
      and [E2] adjust for steroidogenic up-regulation through down-regulation of the
      estrogen-receptor pathway. In this prospective study, prolonged administration of
      [E2+NETA] and to a lesser extent of [E2] but not [T] were associated in otherwise
      healthy breast tissue with a change in the expression of genes putatively
      involved in breast cancer. Our data suggest that normal mammary cells triggered
      by [E2+NETA] adjust for steroidogenic up-regulation through down-regulation of
      the estrogen-receptor pathway. This feasibility study provides the basis for
      whole genome analyses to identify novel markers involved in increased breast
      cancer risk.

PMID- 21956103
TI  - Cycling thalamic stimulation, neuronal entropy, and tremor.

PMID- 21956104
TI  - Mutant profilin suppresses mutant actin-dependent mitochondrial phenotype in
      Saccharomyces cerevisiae.
AB  - In the Saccharomyces cerevisiae actin-profilin interface, Ala(167) of the actin
      barbed end W-loop and His(372) near the C terminus form a clamp around a profilin
      segment containing residue Arg(81) and Tyr(79). Modeling suggests that altering
      steric packing in this interface regulates actin activity. An actin A167E
      mutation could increase interface crowding and alter actin regulation, and A167E
      does cause growth defects and mitochondrial dysfunction. We assessed whether a
      profilin Y79S mutation with its decreased mass could compensate for actin A167E
      crowding and rescue the mutant phenotype. Y79S profilin alone caused no growth
      defect in WT actin cells under standard conditions in rich medium and rescued the
      mitochondrial phenotype resulting from both the A167E and H372R actin mutations
      in vivo consistent with our model. Rescue did not result from effects of profilin
      on actin nucleotide exchange or direct effects of profilin on actin
      polymerization. Polymerization of A167E actin was less stimulated by formin Bni1
      FH1-FH2 fragment than was WT actin. Addition of WT profilin to mixtures of A167E
      actin and formin fragment significantly altered polymerization kinetics from
      hyperbolic to a decidedly more sigmoidal behavior. Substitution of Y79S profilin
      in this system produced A167E behavior nearly identical to that of WT actin.
      A167E actin caused more dynamic actin cable behavior in vivo than observed with
      WT actin. Introduction of Y79S restored cable movement to a more normal
      phenotype. Our studies implicate the importance of the actin-profilin interface
      for formin-dependent actin and point to the involvement of formin and profilin in
      the maintenance of mitochondrial integrity and function.

PMID- 21956105
TI  - Cooperation of p40(phox) with p47(phox) for Nox2-based NADPH oxidase activation
      during Fcgamma receptor (FcgammaR)-mediated phagocytosis: mechanism for
      acquisition of p40(phox) phosphatidylinositol 3-phosphate (PI(3)P) binding.
AB  - During activation of the phagocyte (Nox2-based) NADPH oxidase, the cytoplasmic
      Phox complex (p47(phox)-p67(phox)-p40(phox)) translocates and associates with the
      membrane-spanning flavocytochrome b(558). It is unclear where (in cytoplasm or on
      membranes), when (before or after assembly), and how p40(phox) acquires its
      PI(3)P-binding capabilities. We demonstrated that in addition to conformational
      changes induced by H(2)O(2) in the cytoplasm, p40(phox) acquires PI(3)P-binding
      through direct or indirect membrane targeting. We also found that p40(phox) is
      essential when p47(phox) is partially phosphorylated during FcgammaR-mediated
      oxidase activation; however, p40(phox) is less critical when p47(phox) is
      adequately phosphorylated, using phosphorylation-mimicking mutants in
      HEK293(Nox2/FcgammaRIIa) and RAW264.7(p40/p47KD) cells. Moreover, PI binding to
      p47(phox) is less important when the autoinhibitory PX-PB1 domain interaction in
      p40(phox) is disrupted or when p40(phox) is targeted to membranes. Furthermore,
      we suggest that high affinity PI(3)P binding of the p40(phox) PX domain is
      critical during its accumulation on phagosomes, even when masked by the PB1
      domain in the resting state. Thus, in addition to mechanisms for directly
      acquiring PI(3)P binding in the cytoplasm by H(2)O(2), p40(phox) can acquire
      PI(3)P binding on targeted membranes in a p47(phox)-dependent manner and
      functions both as a "carrier" of the cytoplasmic Phox complex to phagosomes and
      an "adaptor" of oxidase assembly on phagosomes in cooperation with p47(phox),
      using positive feedback mechanisms.

PMID- 21956106
TI  - CcmI subunit of CcmFHI heme ligation complex functions as an apocytochrome c
      chaperone during c-type cytochrome maturation.
AB  - Cytochrome c maturation (Ccm) is a sophisticated post-translational process. It
      occurs after translocation of apocytochromes c to the p side of energy
      transducing membranes and forms stereo-specific thioether bonds between the vinyl
      groups of heme b (protoporphyrin IX-Fe) and the thiol groups of cysteines at
      their conserved heme binding sites. In many organisms this process involves up to
      10 (CcmABCDEFGHI and CcdA) membrane proteins. One of these proteins is CcmI,
      which has an N-terminal membrane-embedded domain with two transmembrane helices
      and a large C-terminal periplasmic domain with protein-protein interaction
      motifs. Together with CcmF and CcmH, CcmI forms a multisubunit heme ligation
      complex. How the CcmFHI complex recognizes its apocytochrome c substrates
      remained unknown. In this study, using Rhodobacter capsulatus apocytochrome c(2)
      as a Ccm substrate, we demonstrate for the first time that CcmI binds
      apocytochrome c(2) but not holocytochrome c(2). Mainly the C-terminal portions of
      both CcmI and apocytochrome c(2) mediate this binding. Other physical
      interactions via the conserved structural elements in apocytochrome c(2), like
      the heme ligating cysteines or heme iron axial ligands, are less crucial.
      Furthermore, we show that the N-terminal domain of CcmI can also weakly bind
      apocytochrome c(2), but this interaction requires a free thiol group at
      apocytochrome c(2) heme binding site. We conclude that the CcmI subunit of the
      CcmFHI complex functions as an apocytochrome c chaperone during the Ccm process
      used by proteobacteria, archaea, mitochondria of plants and red algae.

PMID- 21956107
TI  - A conserved acidic motif is crucial for enzymatic activity of protein O
      mannosyltransferases.
AB  - Protein O-mannosylation is an essential modification in fungi and mammals. It is
      initiated at the endoplasmic reticulum by a conserved family of dolichyl
      phosphate mannose-dependent protein O-mannosyltransferases (PMTs). PMTs are
      integral membrane proteins with two hydrophilic loops (loops 1 and 5) facing the
      endoplasmic reticulum lumen. Formation of dimeric PMT complexes is crucial for
      mannosyltransferase activity, but the direct cause is not known to date. In
      bakers' yeast, O-mannosylation is catalyzed largely by heterodimeric Pmt1p-Pmt2p
      and homodimeric Pmt4p complexes. To further characterize Pmt1p-Pmt2p complexes,
      we developed a photoaffinity probe based on the artificial mannosyl acceptor
      substrate Tyr-Ala-Thr-Ala-Val. The photoreactive probe was preferentially cross
      linked to Pmt1p, and deletion of the loop 1 (but not loop 5) region abolished
      this interaction. Analysis of Pmt1p loop 1 mutants revealed that especially Glu
      78 is crucial for binding of the photoreactive probe. Glu-78 belongs to an Asp
      Glu motif that is highly conserved among PMTs. We further demonstrate that single
      amino acid substitutions in this motif completely abolish activity of Pmt4p
      complexes. In contrast, both acidic residues need to be exchanged to eliminate
      activity of Pmt1p-Pmt2p complexes. On the basis of our data, we propose that the
      loop 1 regions of dimeric complexes form part of the catalytic site.

PMID- 21956108
TI  - ADAM9 inhibition increases membrane activity of ADAM10 and controls alpha
      secretase processing of amyloid precursor protein.
AB  - Prodomains of A disintegrin and metalloproteinase (ADAM) metallopeptidases can
      act as highly specific intra- and intermolecular inhibitors of ADAM catalytic
      activity. The mouse ADAM9 prodomain (proA9; amino acids 24-204), expressed and
      characterized from Escherichia coli, is a competitive inhibitor of human ADAM9
      catalytic/disintegrin domain with an overall inhibition constant of 280 +/- 34 nM
      and high specificity toward ADAM9. In SY5Y neuroblastoma cells overexpressing
      amyloid precursor protein, proA9 treatment reduces the amount of endogenous
      ADAM10 enzyme in the medium while increasing membrane-bound ADAM10, as shown both
      by Western and activity assays with selective fluorescent peptide substrates
      using proteolytic activity matrix analysis. An increase in membrane-bound ADAM10
      generates higher levels of soluble amyloid precursor protein alpha in the medium,
      whereas soluble amyloid precursor protein beta levels are decreased,
      demonstrating that inhibition of ADAM9 increases alpha-secretase activity on the
      cell membrane. Quantification of physiological ADAM10 substrates by a proteomic
      approach revealed that substrates, such as epidermal growth factor (EGF), HER2,
      osteoactivin, and CD40-ligand, are increased in the medium of BT474 breast tumor
      cells that were incubated with proA9, demonstrating that the regulation of ADAM10
      by ADAM9 applies for many ADAM10 substrates. Taken together, our results
      demonstrate that ADAM10 activity is regulated by inhibition of ADAM9, and this
      regulation may be used to control shedding of amyloid precursor protein by
      enhancing alpha-secretase activity, a key regulatory step in the etiology of
      Alzheimer disease.

PMID- 21956109
TI  - Analysis of mannose 6-phosphate uncovering enzyme mutations associated with
      persistent stuttering.
AB  - GlcNAc-1-phosphodiester-N-acetylglucosaminidase ("uncovering enzyme" (UCE); EC
      3.1.4.45) is a Golgi enzyme that mediates the second step in the synthesis of the
      mannose 6-phosphate lysosomal targeting signal on acid hydrolases. Recently,
      three mutations (two missense and one deletion/frameshift) in the NAGPA gene that
      encodes UCE have been identified in individuals with persistent stuttering. We
      now demonstrate that each mutation leads to lower cellular UCE activity. The
      p.R328C mutation impairs folding in the endoplasmic reticulum, resulting in
      degradation of a significant portion by the proteasomal system. The p.H84Q
      mutation also impairs folding and, in addition, decreases the specific activity
      of the enzyme that folds sufficiently to traffic to the Golgi. The p.F513SfsX113
      frameshift mutation adds 113 amino acids to the C terminus of the cytoplasmic
      tail of the protein, including a VWLL sequence that causes rapid degradation via
      the proteasomal system. These biochemical findings extend the genetic data
      implicating mutations in the NAGPA gene in the persistent stuttering phenotype.

PMID- 21956110
TI  - Cooperative regulation of the Vibrio vulnificus nan gene cluster by NanR protein,
      cAMP receptor protein, and N-acetylmannosamine 6-phosphate.
AB  - The nan cluster of Vibrio vulnificus, a food-borne pathogen, consists of two
      divergently transcribed operons, nanT(PSL)AR and nanEK nagA, required for
      transport and catabolism of N-acetylneuraminic acid (Neu5Ac). A mutation of nanR
      abolished the extensive lag phase observed for the bacteria growing on Neu5Ac and
      increased transcription of nanT(P) and nanE, suggesting that NanR is a
      transcriptional repressor of both nan operons. Intracellular accumulation of
      Neu5Ac was dependent on the carbon source, implying that the nan operons are also
      subject to catabolite repression. Hence, cAMP receptor protein (CRP) appeared to
      activate and repress transcription of nanT(PSL)AR and nanEK nagA, respectively.
      Direct bindings of NanR and CRP to the nanT(P)-nanE intergenic DNA were
      demonstrated by EMSA. Two adjacent NanR-binding sites centered at +44.5 and -10
      and a CRP-binding site centered at -60.5 from the transcription start site of
      nanT(P) were identified by DNase I protection assays. Mutagenesis approaches, in
      vitro transcription, and isothermal titration calorimetry experiments
      demonstrated that N-acetylmannosamine 6-phosphate specifically binds to NanR and
      functions as the inducer of the nan operons. The combined results propose a model
      in which NanR, CRP, and N-acetylmannosamine 6-phosphate cooperate for precise
      adjustment of the expression level of the V. vulnificus nan cluster.

PMID- 21956111
TI  - Internalization of exogenous cystatin F supresses cysteine proteases and induces
      the accumulation of single-chain cathepsin L by multiple mechanisms.
AB  - Cystatin F is an unusual member of the cystatin family of protease inhibitors,
      which is made as an inactive dimer and becomes activated by proteolysis in the
      endo/lysosome pathway of the immune cells that produce it. However a proportion
      is secreted and can be taken up and activated by other cells. We show here that
      cystatin F acquired in this way induces a dramatic accumulation of the single
      chain form of cathepsin L (CatL). Cystatin F was observed in the same cellular
      compartments as CatL and was tightly complexed with CatL as determined by co
      precipitation studies. The observed accumulation of single-chain CatL was partly
      due to cystatin F-mediated inhibition of the putative single-chain to two-chain
      CatL convertase AEP/legumain and partly to general suppression of cathepsin
      activity. Thus, cystatin F stabilizes CatL leading to the dramatic accumulation
      of an inactive complex composed either of the single-chain or two-chain form
      depending on the capacity of cystatin F to inhibit AEP. Cross-transfer of
      cystatin F from one cell to another may therefore attenuate potentially harmful
      effects of excessive CatL activity while paradoxically, inducing accumulation of
      CatL protein. Finally, we confirmed earlier data (Beers, C., Honey, K., Fink, S.,
      Forbush, K., and Rudensky, A. (2003) J. Exp. Med. 197, 169-179) showing a loss of
      CatL activity, but not of CatL protein, in macrophages activated with IFNgamma.
      However, we found equivalent loss of CatL activity in wild type and cystatin F
      null macrophages suggesting that an inhibitory activity other than cystatin F
      quenches CatL activity in activated macrophages.

PMID- 21956112
TI  - The unstructured C-terminal tail of yeast Dpb11 (human TopBP1) protein is
      dispensable for DNA replication and the S phase checkpoint but required for the
      G2/M checkpoint.
AB  - Budding yeast Dpb11 (human TopBP1, fission yeast Cut5) is an essential protein
      required for replisome assembly and for the DNA damage checkpoint. Previous
      studies with the temperature-sensitive dpb11-1 allele, truncated at amino acid
      583 of the 764-amino acid protein, have suggested the model that Dpb11 couples
      DNA replication to the replication checkpoint. However, the dpb11-1 allele shows
      distinct replication defects even at permissive temperatures. Here, we determine
      that the 1-600-amino acid domain of DPB11 is both required and sufficient for
      full replication function of Dpb11 but that this domain is defective for
      activation of the principal checkpoint kinase Mec1 (human ataxia telangiectasia
      and Rad3-related) in vitro and in vivo. Remarkably, mutants of DPB11 that leave
      its replication function intact but abrogate its ability to activate Mec1 are
      proficient for the replication checkpoint, but they are compromised for the
      G(2)/M DNA damage checkpoint. These data suggest that replication checkpoint
      defects may result indirectly from defects in replisome assembly. Two conserved
      aromatic amino acids in the C terminus of Dpb11 are critical for Mec1 activation
      in vitro and for the G(2)/M checkpoint in yeast. Together with aromatic motifs
      identified previously in the Ddc1 subunit of 9-1-1, another activator of Mec1
      kinase, they define a consensus structure for Mec1 activation.

PMID- 21956113
TI  - Mechanical regulation of glycogen synthase kinase 3beta (GSK3beta) in mesenchymal
      stem cells is dependent on Akt protein serine 473 phosphorylation via mTORC2
      protein.
AB  - Mechanical signals can inactivate glycogen synthase kinase 3beta (GSK3beta),
      resulting in stabilization of beta-catenin. This signaling cascade is necessary
      for the inhibition of adipogenesis in mesenchymal stem cells (MSC) that is
      produced by a daily strain regimen. We investigated whether Akt is the
      mechanically activated kinase responsible for phosphorylation and inactivation of
      GSK3beta in MSC. Mechanical strain (2% magnitude, 0.17 Hz) induced
      phosphorylation of Akt at Ser-473 and Thr-308 in parallel with phosphorylation of
      GSK3beta at Ser-9. Inhibiting Akt (Akt1/2 kinase inhibitor treatment or Akt
      knockdown) prevented strain-induced phosphorylation of GSK3beta at Ser-9.
      Inhibition of PI3K prevented Thr-308 phosphorylation, but strain-induced Ser-473
      phosphorylation was measurable and induced phosphorylation of GSK3beta,
      suggesting that Ser-473 phosphorylation is sufficient for the downstream
      mechanoresponse. As Rictor/mTORC2 (mammalian target of rapamycin complex 2) is
      known to transduce phosphorylation of Akt at Ser-473 by insulin, we investigated
      whether it contributes to strain-induced Ser-473 phosphorylation. Phosphorylation
      of Ser-473 by both mechanical and insulin treatment in MSC was prevented by the
      mTOR inhibitor KU0063794. When mTORC2 was blocked, mechanical GSK3beta
      inactivation was prevented, whereas insulin inhibition of GSK3beta was still
      measured in the absence of Ser-473 phosphorylation, presumably through
      phosphorylation of Akt at Thr-308. In sum, mechanical input initiates a signaling
      cascade that is uniquely dependent on mTORC2 activation and phosphorylation of
      Akt at Ser-473, an effect sufficient to cause inactivation of GSK3beta. Thus,
      mechanical regulation of GSK3beta downstream of Akt is dependent on
      phosphorylation of Akt at Ser-473 in a manner distinct from that of growth
      factors. As such, Akt reveals itself to be a pleiotropic signaling molecule whose
      downstream targets are differentially regulated depending upon the nature of the
      activating input.

PMID- 21956114
TI  - Tyrosine phosphorylation as a conformational switch: a case study of integrin
      beta3 cytoplasmic tail.
AB  - Reversible protein phosphorylation is vital for many fundamental cellular
      processes. The actual impact of adding and removing phosphate group(s) is 3-fold:
      changes in the local/global geometry, alterations in the electrostatic potential
      and, as the result of both, modified protein-target interactions. Here we present
      a comprehensive structural investigation of the effects of phosphorylation on the
      conformational as well as functional states of a crucial cell surface receptor,
      alpha(IIb)beta(3) integrin. We have analyzed phosphorylated (Tyr(747) and
      Tyr(759)) beta(3) integrin cytoplasmic tail (CT) primarily by NMR, and our data
      demonstrate that under both aqueous and membrane-mimetic conditions,
      phosphorylation causes substantial conformational rearrangements. These changes
      originate from novel ionic interactions and revised phospholipid binding. Under
      aqueous conditions, the critical Tyr(747) phosphorylation prevents beta(3)CT from
      binding to its heterodimer partner alpha(IIb)CT, thus likely maintaining an
      activated state of the receptor. This conclusion was tested in vivo and confirmed
      by integrin-dependent endothelial cells adhesion assay. Under membrane-mimetic
      conditions, phosphorylation results in a modified membrane embedding
      characterized by significant changes in the secondary structure pattern and the
      overall fold of beta(3)CT. Collectively these data provide unique molecular
      insights into multiple regulatory roles of phosphorylation.

PMID- 21956115
TI  - Demonstration that drug-targeted down-regulation of MYC in non-Hodgkins lymphoma
      is directly mediated through the promoter G-quadruplex.
AB  - Most transcription of the MYC proto-oncogene initiates in the near upstream
      promoter, within which lies the nuclease hypersensitive element (NHE) III(1)
      region containing the CT-element. This dynamic stretch of DNA can form at least
      three different topologies: single-stranded DNA, double-stranded DNA, or higher
      order secondary structures that silence transcription. In the current report, we
      identify the ellipticine analog GQC-05 (NSC338258) as a high affinity, potent,
      and selective stabilizer of the MYC G-quadruplex (G4). In cells, GQC-05 induced
      cytotoxicity with corresponding decreased MYC mRNA and altered protein binding to
      the NHE III(1) region, in agreement with a G4 stabilizing compound. We further
      describe a unique feature of the Burkitt's lymphoma cell line CA46 that allowed
      us to clearly demonstrate the mechanism and location of action of GQC-05 within
      this region of DNA and through the G4. Most importantly, these data present, as
      far as we are aware, the most direct evidence of intracellular G4-mediated
      control of a particular promoter.

PMID- 21956118
TI  - Giant osteochondroma of axis in a child with multiple hereditary exostoses:  case
      report and review of literature.
AB  - Though osteochondromas are the most common benign bone tumour, their spinal
      involvement is less frequent. We report a case of osteochondroma in a 5-year-old
      female child with multiple hereditary exostoses that originated from posterior
      elements of C2 vertebra, not involving spinal canal and caused restriction of
      neck movement. It was excised from its base without disturbing the continuity of
      lamina. Two years later she had normal neck movements without any recurrence. The
      rarity of this tumour at this location, with such a large size at an early age,
      makes this article unique.

PMID- 21956117
TI  - Structural analyses of a purine biosynthetic enzyme from Mycobacterium
      tuberculosis reveal a novel bound nucleotide.
AB  - Enzymes of the de novo purine biosynthetic pathway have been identified as
      essential for the growth and survival of Mycobacterium tuberculosis and thus have
      potential for the development of anti-tuberculosis drugs. The final two steps of
      this pathway are carried out by the bifunctional enzyme 5-aminoimidazole-4
      carboxamide ribonucleotide transformylase/inosine monophosphate cyclohydrolase
      (ATIC), also known as PurH. This enzyme has already been the target of anti
      cancer drug development. We have determined the crystal structures of the M.
      tuberculosis ATIC (Rv0957) both with and without the substrate 5-aminoimidazole-4
      carboxamide ribonucleotide, at resolutions of 2.5 and 2.2 A, respectively. As for
      other ATIC enzymes, the protein is folded into two domains, the N-terminal domain
      (residues 1-212) containing the cyclohydrolase active site and the C-terminal
      domain (residues 222-523) containing the formyltransferase active site. An
      adventitiously bound nucleotide was found in the cyclohydrolase active site in
      both structures and was identified by NMR and mass spectral analysis as a novel 5
      formyl derivative of an earlier intermediate in the biosynthetic pathway 4
      carboxy-5-aminoimidazole ribonucleotide. This result and other studies suggest
      that this novel nucleotide is a cyclohydrolase inhibitor. The dimer formed by M.
      tuberculosis ATIC is different from those seen for human and avian ATICs, but it
      has a similar ~50-A separation of the two active sites of the bifunctional
      enzyme. Evidence in M. tuberculosis ATIC for reactivity of half-the-sites in the
      cyclohydrolase domains can be attributed to ligand-induced movements that
      propagate across the dimer interface and may be a common feature of ATIC enzymes.

PMID- 21956119
TI  - Mitral annulus dynamics early after valve repair: preliminary observations of the
      effect of resectional versus non-resectional approaches.
AB  - BACKGROUND: Mitral repair is recommended for patients with significant organic
      mitral regurgitation (MR). The nonresectional dynamic mitral valve repair (NVR)
      method involves a complete flexible ring and artificial chordal insertion but
      without leaflet resection or annular plication. The aim of this study was to
      compare changes in mitral annular structure and function after the NVR technique
      with those after a resectional mitral valve repair (RVR) method, which involves
      leaflet resection and annuloplasty with a partial flexible ring. METHODS:
      Patients with organic severe MR undergoing mitral valve repair with either
      technique underwent three-dimensional transesophageal echocardiography before and
      after surgery. The mitral annulus was tracked offline and measured throughout the
      cardiac cycle. Mitral leaflet mobility was also measured. RESULTS: Fifteen
      patients underwent repair with NVR, and 13 underwent repair with RVR (age, 56 vs
      61 years, respectively). Both operations reduced mitral annular area
      significantly (maximum area reduction, from 18.5 +/- 4.6 to 6.6 +/- 1.7 cm(2) and
      from 20.1 +/- 4.8 to 6 +/- 1.5 cm(2) with the NVR and RVR techniques,
      respectively; P < .001). In contrast to RVR, patients who underwent NVR
      maintained dynamic changes in mitral annular area, circumference, and anterior
      posterior diameter during the cardiac cycle. Mitral leaflet mobility was reduced
      with both techniques, but posterior leaflet mobility was restricted with RVR.
      CONCLUSIONS: The size of the mitral annulus is reduced after repair with either
      surgical approach. Compared with resectional valve repair, more dynamic changes
      in the structure of the mitral annulus are maintained during the cardiac cycle
      with the NVR technique early postoperatively, along with more preserved motion of
      the posterior leaflet.

PMID- 21956116
TI  - HIV-1 Tat protein promotes neuronal dysfunction through disruption of microRNAs.
AB  - Over the last decade, small noncoding RNA molecules such as microRNAs (miRNAs)
      have emerged as critical regulators in the expression and function of eukaryotic
      genomes. It has been suggested that viral infections and neurological disease
      outcome may also be shaped by the influence of small RNAs. This has prompted us
      to suggest that HIV infection alters the endogenous miRNA expression patterns,
      thereby contributing to neuronal deregulation and AIDS dementia. Therefore, using
      primary cultures and neuronal cell lines, we examined the impact of a viral
      protein (HIV-1 Tat) on the expression of miRNAs due to its characteristic
      features such as release from the infected cells and taken up by noninfected
      cells. Using microRNA array assay, we demonstrated that Tat deregulates the
      levels of several miRNAs. Interestingly, miR-34a was among the most highly
      induced miRNAs in Tat-treated neurons. Tat also decreases the levels of miR-34a
      target genes such as CREB protein as shown by real time PCR. The effect of Tat
      was neutralized in the presence of anti-miR-34a. Using in situ hybridization
      assay, we found that the levels of miR-34a increase in Tat transgenic mice when
      compared with the parental mice. Therefore, we conclude that deregulation of
      neuronal functions by HIV-1 Tat protein is miRNA-dependent.

PMID- 21956120
TI  - Chemically-modified graphenes for oxidation of DNA bases: analytical parameters.
AB  - We studied the electroanalytical performances of chemically-modified graphenes
      (CMGs) containing different defect densities and amounts of oxygen-containing
      groups, namely graphite oxide (GPO), graphene oxide (GO), thermally reduced
      graphene oxide (TR-GO) and electrochemically reduced graphene oxide (ER-GO) by
      comparing the sensitivity, selectivity, linearity and repeatability towards the
      oxidation of DNA bases. We have observed that for differential pulse voltammetric
      (DPV) detection of adenine and cytosine, all CMGs showed enhanced sensitivity to
      oxidation, while for guanine and thymine, ER-GO and TR-GO exhibited much improved
      sensitivity over bare glassy carbon (GC) as well as over GPO and GO. There is
      also significant selectivity enhancement when using GPO for adenine and TR-GO for
      thymine. Our results have uncovered that the differences in surface
      functionalities, structure and defects of various CMGs largely influence their
      electrochemical behaviour in detecting the oxidation of DNA bases. The findings
      in this report will provide a useful guide for the future development of label
      free electrochemical devices for DNA analysis.

PMID- 21956121
TI  - Analysis of gene expression in atopic dermatitis using a microabrasive method.

PMID- 21956122
TI  - Review and cross-validation of gene expression signatures and melanoma prognosis.
AB  - In melanoma, there is an urgent need to identify novel biomarkers with prognostic
      performance superior to traditional clinical and histological parameters. Gene
      expression-based prognostic signatures offer promise, but studies have been
      challenged by sample scarcity, cohort heterogeneity, and doubts about the
      efficacy of such signatures relative to current clinical practices. Motivated by
      new studies that have begun to address these challenges, we reviewed prognostic
      signatures derived from gene expression microarray analysis of human melanoma
      tissue. We used REMARK-based criteria to select the most relevant studies and
      directly compared their signature gene lists. Through functional ontology
      enrichment analysis, we observed that these independent data sets converge in
      part upon immune response processes and the G-protein signaling NRAS-regulation
      pathway, both important in melanoma development and progression. The signatures
      correctly predicted patient outcome in independent gene expression data sets with
      some notably low misclassification rates, particularly among studies involving
      more advanced-stage tumors. This successful cross-validation indicates that gene
      expression analysis-based signatures are becoming translationally relevant to
      care of melanoma patients, as well as improving understanding of the aspects of
      melanoma biology that determine patient outcome.

PMID- 21956123
TI  - N(E)-(carboxymethyl)lysine modification of elastin alters its biological
      properties: implications for the accumulation of abnormal elastic fibers in
      actinic elastosis.
AB  - Accumulation of degenerated elastic fibers in the sun-exposed skin designated as
      actinic elastosis is a histological hallmark of photodamaged skin. Previous
      studies have indicated that the elastic fibers of actinic elastosis interact with
      lysozyme and are modified by N(E)-(carboxymethyl)lysine (CML), one of the major
      advanced glycation end products (AGEs). We studied here how CML modification of
      elastin is involved in the pathogenesis of actinic elastosis. The CML-modified
      insoluble elastin became resistant to neutrophil elastase digestion, which was
      reversed by treatment with aminoguanidine, a potent inhibitor of AGE formation.
      In a temperature-dependent aggregation assay, CML-modified elastin rapidly formed
      self-aggregates, the size of which was larger than unmodified elastin. The
      elastic fiber sheets prepared from CML-modified alpha-elastin showed 3D wider
      diameter, tortuous appearance, and decreased elasticity on tensile tests. The CML
      modified alpha-elastin, but not unmodified alpha-elastin, was found to bind to
      lysozyme in vitro, supporting the immunohistochemical findings that the
      antibodies for lysozyme and CML reacted simultaneously with the elastic fibers of
      actinic elastosis and UV-irradiated skin. The glycated elastin is likely to cause
      the accumulation of abnormally aggregated elastic fibers and unusual interaction
      with lysozyme in actinic elastosis.

PMID- 21956124
TI  - Fibronectin expression determines skin cell motile behavior.
AB  - Mouse keratinocytes migrate significantly slower than their human counterparts in
      vitro on uncoated surfaces. We tested the hypothesis that this is a consequence
      of differences in the extracellular matrix (ECM) that cells deposit. In support
      of this, human keratinocyte motility was markedly reduced when plated onto the
      ECM of mouse skin cells, whereas the latter cells migrated faster when plated
      onto human keratinocyte ECM. The ECM of mouse and human keratinocytes contained
      similar levels of the alpha3 laminin subunit of laminin-332. However, mouse skin
      cells expressed significantly more fibronectin (FN) than human cells. To assess
      whether FN is a motility regulator, we used small interfering RNA (siRNA) to
      reduce the expression of FN in mouse keratinocytes. The treated mouse
      keratinocytes moved significantly more rapidly than wild-type mouse skin cells.
      Moreover, the FN-depleted mouse cell ECM supported increased migration of both
      mouse and human keratinocytes. Furthermore, the motility of human keratinocytes
      was slowed when plated onto FN-coated substrates or human keratinocyte ECM
      supplemented with FN in a dose-dependent manner. Consistent with these findings,
      the ECM of alpha3 integrin-null keratinocytes, which also migrated faster than
      wild-type cells, was FN deficient. Our results provide evidence that FN is a
      brake to skin cell migration supported by laminin-332-rich matrices.

PMID- 21956126
TI  - CHEK2*1100delC and risk of malignant melanoma: Danish and German studies and meta
      analysis.
AB  - It is possible that reduced function of DNA repair and cell-cycle control genes
      increases the individual susceptibility to malignant melanoma. As CHEK2 is a cell
      cycle master controller, we tested the hypothesis that heterozygosity for the
      frameshift alteration CHEK2*1100delC is associated with increased risk of
      malignant melanoma. First, we performed case-control studies of 1,152 Danish and
      752 German individuals with malignant melanoma compared with 9,142 Danish and
      3,718 German controls. Second, we performed a meta-analysis of CHEK2*1100delC and
      malignant melanoma, involving 2,619 cases and 17,481 controls. Third, we examined
      the risk of malignant melanoma associated with CHEK2*1100delC heterozygosity in
      an analysis stratified for sun exposure, as well as for subtype and location on
      the body. The odds ratios for malignant melanoma for CHEK2(*)1100del
      heterozygotes compared with those for noncarriers were 2.01 (95% confidence
      interval (CI), 1.03-3.91) in Danes, 1.42 (95% CI, 0.46-4.31) in Germans, and 1.79
      (95% CI, 1.02-3.17) in Danes and Germans combined. In a meta-analysis, the odds
      ratio of malignant melanoma for CHEK2*1100delC heterozygotes compared with that
      for noncarriers was 1.81 (95% CI, 1.07-3.05). Stratifications did not alter these
      results. CHEK2*1100delC heterozygotes have a twofold risk of malignant melanoma
      compared with noncarriers.

PMID- 21956127
TI  - Thyrotropin-releasing hormone selectively stimulates human hair follicle
      pigmentation.
AB  - In amphibians, thyrotropin-releasing hormone (TRH) stimulates skin melanophores
      by inducing secretion of alpha-melanocyte-stimulating hormone in the pituitary
      gland. However, it is unknown whether this tripeptide neurohormone exerts any
      direct effects on pigment cells, namely, on human melanocytes, under
      physiological conditions. Therefore, we have investigated whether TRH stimulates
      pigment production in organ-cultured human hair follicles (HFs), the epithelium
      of which expresses both TRH and its receptor, and/or in full-thickness human skin
      in situ. TRH stimulated melanin synthesis, tyrosinase transcription and activity,
      melanosome formation, melanocyte dendricity, gp100 immunoreactivity, and
      microphthalmia-associated transcription factor expression in human HFs in a
      pituitary gland-independent manner. TRH also stimulated proliferation, gp100
      expression, tyrosinase activity, and dendricity of isolated human HF melanocytes.
      However, intraepidermal melanogenesis was unaffected. As TRH upregulated the
      intrafollicular production of "pituitary" neurohormones (proopiomelanocortin
      transcription and ACTH immunoreactivity) and as agouti-signaling protein
      counteracted TRH-induced HF pigmentation, these pigmentary TRH effects may be
      mediated in part by locally generated melanocortins and/or by MC-1 signaling. Our
      study introduces TRH as a novel, potent, selective, and evolutionarily highly
      conserved neuroendocrine factor controlling human pigmentation in situ. This
      physiologically relevant and melanocyte sub-population-specific neuroendocrine
      control of human pigmentation deserves clinical exploration, e.g., for preventing
      or reversing hair graying.

PMID- 21956125
TI  - An adult passive transfer mouse model to study desmoglein 3 signaling in
      pemphigus vulgaris.
AB  - Evidence has accumulated that changes in intracellular signaling downstream of
      desmoglein 3 (Dsg3) may have a significant role in epithelial blistering in the
      autoimmune disease pemphigus vulgaris (PV). Currently, most studies on PV involve
      passive transfer of pathogenic antibodies into neonatal mice that have not
      finalized epidermal morphogenesis, and do not permit analysis of mature hair
      follicles (HFs) and stem cell niches. To investigate Dsg3 antibody-induced
      signaling in the adult epidermis at defined stages of the HF cycle, we developed
      a model with passive transfer of AK23 (a mouse monoclonal pathogenic anti-Dsg3
      antibody) into adult 8-week-old C57Bl/6J mice. Validated using histopathological
      and molecular methods, we found that this model faithfully recapitulates major
      features described in PV patients and PV models. Two hours after AK23 transfer,
      we observed widening of intercellular spaces between desmosomes and EGFR
      activation, followed by increased Myc expression and epidermal
      hyperproliferation, desmosomal Dsg3 depletion, and predominant blistering in HFs
      and oral mucosa. These data confirm that the adult passive transfer mouse model
      is ideally suited for detailed studies of Dsg3 antibody-mediated signaling in
      adult skin, providing the basis for investigations on novel keratinocyte-specific
      therapeutic strategies.

PMID- 21956129
TI  - Trichoderma reesei cellobiohydrolase II is associated with the outer membrane
      when overexpressed in Escherichia coli.
AB  - Cellulose degradation is essential for the future production of many advanced
      biofuels. Cellulases from the filamentous fungus Trichoderma reesei are among the
      most efficient enzymes for the hydrolysis of cellulosic materials. One of the
      cellulases from T. reesei, cellobiohydrolase II (CBH2), was studied because of
      its industrial relevance and proven enzymatic activity. Using both crude and
      rigorous membrane fractionation methods we show that full length T. reesei CBH2
      is exclusively localized to the outer membrane when expressed recombinantly in
      Escherichia coli. Even fusing signal sequence-free maltose-binding protein to the
      N-terminus of CBH2, which has been shown to increase solubility of other
      proteins, did not prevent the outer membrane localization of CBH2. These results
      highlight the difficulties in producing fungal cellulases in bacterial hosts and
      provide a stepping stone for future cellulase engineering efforts.

PMID- 21956128
TI  - Oleic acid inhibits store-operated calcium entry in human colorectal
      adenocarcinoma cells.
AB  - AIMS: Much evidence indicates the association between dietary fat and colorectal
      cancer risk. However, most of the studies focus on polyunsaturated fatty acids,
      and little is known about the role of monounsaturated ones and their precise
      mechanism of action. Being store-operated Ca2+ entry (SOCE) a Ca2+ influx pathway
      involved in the control of multiple cellular and physiological processes
      including cell proliferation, we studied the effect of oleic acid in Ca2+ signals
      of colorectal cancer cells, paying particular attention to SOCE. METHODS:
      Carbachol was used to induce SOCE in Fura 2-loaded HT29 cells. We tested a
      saturated fatty acid to compare the physiological relevance of our results.
      RESULTS: We show that oleic acid is a potent inhibitor of SOCE. By contrast,
      stearic acid failed to have a SOCE-inhibitory effect. The SOCE-inhibition induced
      by oleic acid was protein kinase C-independent and restored by albumin. We also
      demonstrated that oleic acid induced increases in [Ca2+](i). The novelty of our
      report is that little variability in the concentration could end in a large
      different physiological effect. CONCLUSIONS: In conclusion, we suggest a
      physiological pathway for the beneficial effect of oleic acid in colon carcinoma
      cells.

PMID- 21956130
TI  - Isolation and characterization of the citrinin biosynthetic gene cluster from
      Monascus aurantiacus.
AB  - Monascus aurantiacus produces high amounts of citrinin which is a mycotoxin with
      nephrotoxic activity. Six putative citrinin biosynthesis genes have been
      discovered in M. purpureus and at least 10 genes are responsible for its
      biosynthesis. However, the sequence of citrinin pathway gene cluster in M.
      aurantiacus has not been reported. Here, the putative sequence of citrinin
      biosynthetic gene cluster was obtained by a PCR-based strategy for screening a
      genome fosmid library of M. aurantiacus. A sequence of 43 kb revealed 16 ORFs
      including the six putative biosynthetic genes reported previous. The putative
      gene cluster consists of a polytekide synthetase encoding one PKS module, an
      oxidoreductase gene, three dehydrogenase genes, an acyl-coenzyme A synthetase
      gene, a membrane transport protein gene, a transcriptional activator gene as well
      as genes encoding proteins of undefined function.

PMID- 21956131
TI  - Introgression of the heterologous nuclear DNAs and efficacious compositions from
      Swertia tetraptera Maxim. into Bupleurum scorzonerifolium Willd. via somatic
      hybridization.
AB  - Swertia tetraptera Maxim. is an important source of secoiridoid glucosides. To
      produce these pharmacologically valuable compounds heterologously in somatic
      hybrid cell lines, S. tetraptera protoplasts were irradiated with various doses
      of UV light and fused with protoplasts from a long-term cell line of Bupleurum
      scorzonerifolium Willd. This recipient was chosen as the cell line is
      cytogenetically stable and fast growing; furthermore, protoplasts isolated from
      the cell line are readily regenerable. From a set of 86 putative hybrid calli,
      only two were able to regenerate viable green plants. The hybridity of the 19 of
      the 86 selections was revealed by a combined isozyme and RAPD analysis, supported
      by a karyotypic study based on genomic in situ hybridization (GISH). Clone I-3
      contained 0.014% swertiamarin while the regenerants had 0.069% swertiamarin and
      0.409% gentiopicroside while the III-4 plants contained only 0.015%
      gentiopicroside.

PMID- 21956132
TI  - Research on the quality of abdominal surgical nursing care: a scoping review.
AB  - Various health care measures have been identified over the years as indicators of
      health care quality. However, studies evaluating the quality of nursing care
      among different patient groups are scarce. Patients undergoing abdominal surgery
      may be a group that has different views, needs, expectations, and evaluation of
      the quality of nursing care. Literature search was conducted using the following
      key words in various combinations in the Medline, PsycInfo, CINAHL, and Cochrane
      databases: quality of nursing, surgical or perioperative, abdominal or abdomen.
      The studies that focused on the evaluation of surgical nursing care with a study
      sample of patients undergoing abdominal surgery and nurses taking care of these
      patients were included in this scoping review. In total, 17 research articles
      were analyzed. The analysis revealed that the quality of nursing care was usually
      rated as high according to the perceptions of patients and/or nurses. The
      following factors associated with the quality of nursing care were identified:
      nurse staffing, organizational characteristics, patients' characteristics,
      nurses' characteristics, nursing care needs, and nursing documentation. Further
      research should be focused on the measurement and evaluation of the quality of
      abdominal surgical nursing care from nurses', patients' and their relatives'
      perceptions by using nonexperimental and experimental study designs for gaining
      the knowledge how to improve the quality in practice.

PMID- 21956133
TI  - Use of combined oral contraceptives and headaches.
AB  - OBJECTIVE: The study was designed to examine the certain patterns of combined
      oral contraceptive use in women of childbearing potential and evaluate the
      relationship between the use of combined oral contraceptives and headaches, bad
      habits, type of work, and concomitant diseases. MATERIAL AND METHODS: In total,
      194 randomly selected women aged 18 to 40 years who visited a gynecologist for
      preventive gynecological examination were surveyed. Respondents were categorized
      as combined oral contraceptive users (n=116; study group) and nonusers (n=78;
      control group). An anonymous questionnaire developed by the authors of this study
      and a standardized scale called the Migraine Disability Assessment Scale (MIDAS)
      were used for the survey. RESULTS: A multivariate logistic regression analysis
      demonstrated a significantly higher prevalence of combined oral contraceptive use
      in women older than 20 years (odds ratio, 6.0; 95% CI, 2.6-14), better educated
      women (odds ratio, 5.7; 95% CI, 2.1-15.2), and women reporting a steady sexual
      partner (odds ratio, 4.0; 95% CI, 1.5-11.0). Relationship between headaches and
      use of combined oral contraceptives as well as other factors were analyzed in a
      group of 178 respondents; the rest 16 respondents reported not having headaches
      at all. The prevalence of reported minimal-to-mild and moderate-to-severe impact
      of headaches on daily activities did not differ significantly between the study
      and control groups, women with and without bad habits, and white-collar and blue
      collar groups (P>0.05). However, women with concomitant diseases significantly
      more often reported moderate-to-severe impact on daily activities due to
      headaches (P<0.01). Differences in impact of headaches on daily activities
      between women using combined oral contraceptives containing 20 or less MUg of
      ethinylestradiol and 30 or more MUg of ethinylestradiol did not differ
      significantly. CONCLUSIONS: The prevalence of combined oral contraceptive use was
      higher in women older than 20 years, better educated women, and women reporting a
      steady sexual partner. The impact of headaches on daily activities did not differ
      significantly between the combined oral contraceptive users and nonusers.

PMID- 21956134
TI  - Diagnostic value of conventional visual evoked potentials applied to patients
      with multiple sclerosis.
AB  - OBJECTIVE: The aim of this study was to determine the sensitivity and specificity
      of this classical technique employed at the Hospital of Lithuanian University of
      Health Sciences for the patients with multiple sclerosis and to assess its
      possible correlations with affected neurological systems. MATERIAL AND METHODS:
      Pattern shift visual evoked potentials were recorded in 63 patients with multiple
      sclerosis, 17 (27%) of whom had a history of optic neuritis, and in 63 control
      patients with other neurological diseases. The latencies and amplitudes of P100
      were measured. In total, 126 patients were referred to the inpatient department
      of neurology for differential diagnosis of demyelinating disorders between
      January and December of 2007. RESULTS: Abnormalities of visual evoked potentials
      were observed by 73% more frequently in patients with multiple sclerosis than in
      control patients (alpha=0.05, beta<0.01). The combined monocular/interocular test
      showed a specificity of 90.5% and a sensitivity of 82.5%. The probability of an
      affection of the pyramidal system was 5 times greater (95% CI, 2.2-11.0; P<0.01)
      and the probability of the optic pathways involvement was 4.8 times greater (95%
      CI, 1.9-11.9; P<0.01) in patients with multiple sclerosis than in controls.
      CONCLUSION: Conventional visual evoked potentials must be reappraised in light of
      their diagnostic value in multiple sclerosis given their high diagnostic
      efficiency, relatively easy, short, and cheap implementation, and easy
      availability in everyday clinical practice.

PMID- 21956135
TI  - The impact of medical conditions on the quality of life of survivors at discharge
      from intensive care unit.
AB  - BACKGROUND AND OBJECTIVE: Impaired health-related quality of life (HRQOL) is one
      of the possible outcomes after discharge from an intensive care unit (ICU).
      Evaluation of patient health status on discharge from the ICU would help identify
      factors influencing changes in HRQOL after ICU discharge. The objective of the
      study was to identify whether health state on discharge from prolonged stay in
      the ICU has any influence on survivors' HRQOL 6 months after intensive care.
      MATERIAL AND METHODS: A prospective study of patients with the prolonged length
      of stay (exceeding 7 days) in the ICU was conducted. The study covered the impact
      of organ system dysfunction (SOFA score), number of therapeutic interventions
      (TISS-28 score), and critical illness neuromuscular abnormalities (CINMA) on
      discharge from the ICU on HRQOL 6 months following ICU discharge. RESULTS: In
      total, 137 patients were included in the study. The SOFA score on the last day in
      the ICU was 2.91 (SD, 1.57); the TISS-28 score on the last day in the ICU was
      21.79 (SD, 4.53). Decreased physical functioning (PF) and role physical (RP) were
      identified. Circulatory impairment on discharge from the ICU had an impact on
      decreased PF (P=0.016), role physical (P=0.066), and role emotional (P=0.001).
      Patients with dysfunction in more than one organ system on ICU discharge had
      decreased role emotional (P=0.016). Severe CINMA was diagnosed in 18 patients.
      They had decreased PF (P=0.007) and RP (P=0.019). Patients with the TISS-28 score
      above or equal to 20 points showed lower HRQOL in the PF domain (P=0.077) and
      general health (P=0.038). CONCLUSIONS: HRQOL in patients with prolonged stay in
      the ICU is particularly impaired in the domains of physical functioning and role
      physical. It is associated with circulatory impairment, CINMA, and greater number
      of therapeutic interventions on discharge from the ICU.

PMID- 21956136
TI  - Changes in antibiotic resistance level of nosocomial Pseudomonas aeruginosa
      isolates in the largest university hospital of Lithuania.
AB  - The aim was to estimate changes in the resistance rates of Pseudomonas aeruginosa
      (P. aeruginosa) strains isolated from patients treated in intensive care units of
      the largest university hospital. MATERIALS AND METHODS: Isolates were identified
      with the Phoenix ID system (Becton Dickinson, USA). The minimum inhibitory
      concentration (MIC) of ceftazidime, ciprofloxacin, and amikacin were determined
      by the E-test and evaluated following the recommendations of the Clinical
      Laboratory Standards Institute. RESULTS: In 2003, the proportion of P. aeruginosa
      strains resistant to piperacillin was greatest followed by strains resistant
      gentamicin and ciprofloxacin. In 2008, the resistance rates markedly changed
      being the highest to ciprofloxacin. An increase in the resistance rates to
      ciprofloxacin (+24%, P<0.001) and ceftazidime (+8.3%, P<0.05) was documented. In
      2003, there were 66.7% of P. aeruginosa strains sensitive to all antibiotics
      tested, and this percentage decreased to 47.5% in 2008 (P<0.05). During the
      study, a significant increase in the median MICs for ciprofloxacin and amikacin
      was observed (P<0.001); however, no significant change was documented for
      ceftazidime. CONCLUSIONS: P. aeruginosa remains an important nosocomial pathogen
      with relatively high overall resistance to antimicrobial agents, and the
      resistance level is increasing.

PMID- 21956137
TI  - Genetic variation of the human ACE and ACTN3 genes and their association with
      functional muscle properties in Lithuanian elite athletes.
AB  - BACKGROUND AND OBJECTIVE: Based on the results of many studies, the angiotensin
      converting enzyme (ACE) and the alpha-actinin-3 (ACTN3) genes are considered
      strong candidate genes associated with human physical performance. On the other
      hand, the data regarding the association of the ACE I/D and ACTN3 R/X
      polymorphisms with human physical performance in different populations have been
      conflicting. The objective of our research was to evaluate the significance of
      these genetic variants on muscle performance phenotype in Lithuanian athletes.
      MATERIAL AND METHODS: The study involved 193 Lithuanian elite athletes and 250
      controls from the general Lithuanian population. Genotyping was performed by
      polymerase chain reaction and/or restriction fragment length polymorphism
      analysis. Anthropometric measurements and muscle strength (grip strength and
      vertical jump) were measured. RESULTS: It was determined that ACE I/I and I/D
      genotypes were more frequent in the athlete group compared with the general
      Lithuanian population. The results of grip strength and vertical jump were better
      in the athletes with the ACE I/I and ACTN3 X/X genotype compared with the
      athletes with ACE D/D and ACTN3 R/R, respectively. CONCLUSIONS: The ACE I and
      ACTN3 X alleles determine speed and power for Lithuanian athletes. In line with
      other researchers, it can be confirmed that the absence of a functional ACTN3 in
      fast-twitch muscle fibers is compensated. Lithuanian athletes who are carriers of
      the ACE I/I and I/D as well as ACTN3 X/X and R/X genotypes have the potential to
      achieve better results in power-requiring sports; therefore, the analyzed
      polymorphisms of these genes might be used as the criteria for the sport type
      selection.

PMID- 21956138
TI  - Causes of refraining from buying prescribed medications among the elderly in
      Kaunas, Lithuania.
AB  - BACKGROUND AND OBJECTIVE: Accessibility to medications among the elderly is a
      source of concern in Lithuania and beyond. However, there are no studies carried
      out on this topic in Lithuania. Therefore, the aim of this study was to evaluate
      the causes of refraining from buying prescribed medications among the elderly in
      Kaunas, Lithuania. MATERIAL AND METHODS: The data were collected in a cross
      sectional ABUEL study in 2009. A total of 624 filled-in questionnaires (response
      rate, 48.9%) from the elderly aged 60-84 years living in Kaunas (Lithuania) were
      received. For evaluation of the impact of explanatory variables on the analyzed
      event (binary dependent variable), an Enter model of logistic regression was
      used. RESULTS: The study showed that 32.7% of the respondents refrained from
      buying prescribed medications. The most common reasons (respondents could select
      several options) for this decision were financial problems (48.0%), disappearance
      of problems (40.7%), and fear of side effects (22.5%). Refraining from buying
      prescribed medications was positively associated with age (OR, 0.85; 95% CI, 0.74
      to 0.99). Higher education was associated with a reduced risk of refraining from
      buying prescribed medications due to financial problems (OR, 0.49; 95% CI, 0.31
      to 0.78) and an increased risk of refraining from buying medications due to the
      disappearance of health problems (OR, 1.75; 95% CI, 1.15 to 2.68). An opposite
      association with worries about daily expenses was observed. CONCLUSIONS: Study
      has revealed that one-third of the elderly refrained from buying prescribed
      medications, and the main reasons for this were financial problems and
      disappearance of health problems.

PMID- 21956139
TI  - [Risk of stroke and death after carotid endarterectomy].
AB  - OBJECTIVE: The benefit of carotid endarterectomy is highly dependent on surgical
      risk. The aim of this study was to evaluate the incidence of stroke and death
      after carotid endarterectomy, risk factors for poor outcomes, and importance of
      surgeon's competence. MATERIAL AND METHODS: A total of 790 carotid
      endarterectomies performed in the Vilnius University Emergency Hospital between
      1995 and 2006 were analyzed. Risk factors, neurological symptoms, comorbidities,
      radiologic and angiographic findings, morbidity and mortality, experience and
      volume of a vascular surgeon were prospectively recorded in a database.
      Univariate and multivariable logistic regression and receiver operating
      characteristic curves were used to analyze the data. RESULTS: Among the 790 cases
      studied, in-hospital mortality was 2.2%, and stroke morbidity was 2.4%.
      Postoperative complications were more common in patients with diabetes mellitus
      than without (12% vs. 3.4%, P<0.001) and in patients with any stroke than in
      patients with nonspecific symptoms (10.7% vs. 1.4%, P<0.02). The postoperative
      stroke rate was 10% for a surgeon who performed <6 carotid endarterectomies per
      year and 4.6% for a surgeon who performed >=6 carotid endarterectomies (P=0.02).
      In the multivariate logistic regression, combined mortality and stroke was
      independently predicted by diabetes mellitus (OR, 3.51; 95% CI, 1.60-7.66;
      P=0.002), any stroke (OR, 4.14; 95% CI, 1.57-10.91; P=0.004), and low-volume
      surgeon (OR, 0.32; 95% CI, 0.13-0.78; P=0.013). The receiver operating
      characteristic curve analysis showed an overall predicting value of 0.72.
      CONCLUSIONS: Diabetes mellitus, any stroke, and low-volume vascular surgeon were
      significant predictors for poor outcome after carotid endarterectomy.

PMID- 21956140
TI  - [Scapulohumeral hydatidosis: a new case in Tunisia].
AB  - Osseous hydatidosis is reported in only 0.5-2.5% of the cases. The scapulohumeral
      localization is extremely rare. A 39-year-old woman, born in a rural area of
      Tunisia, presented swelling and tenderness of the left shoulder with limited
      motion 7 days after a minor trauma. Plain radiographs, CT and MRI showed
      osteolytic scapulohumeral lesions, cortical rupture and multiple cysts in the
      muscles, which were suggestive of hydatidosis. Indirect haemagglutination test
      using hydatid antigen was positive (1/280). The patient refused radical surgery
      and underwent resection of axillary cysts. Albendazole was given in the
      recommended dose but was stopped immediately due to hepatic toxicity.
      Scapulohumeral hydatidosis is extremely rare, often invasive and behaves like a
      locally malignant bone tumour. Its treatment is also difficult.

PMID- 21956141
TI  - [Towards the control of the endemic of sleeping sickness in Nola-Bilolo focus,
      Central African Republic].
AB  - Sleeping sickness is more prevalent in three historical regions of Central
      African Republic. Control measures were organized by the colonial authorities
      through health services to fight against this disease and other major diseases.
      Multivariate analysis and the government helped in controlling the disease in the
      focus of Nola-Bilolo, which was formerly hyperendemic. The authors report the
      results of the control measures that resulted in the extinction of the disease in
      this outbreak. This is a retrospective study from 1991 to 2008, and the data were
      collected from the National Program to fight against human African
      trypanosomiasis in Bangui and in the diagnostic and treatment center of Nola. It
      was highly endemic, with more than 300 cases recorded in the year 1991. The
      average number of cases was 200.8 per year between 1992 and 1998. Less than 50
      cases per year were recorded from 2000 to 2006, and no cases have been detected
      since 2007. 69.35% of the patients were actively screened. 5,000 conical
      deltamethrin-impregnated traps (Gouteux and Lancien) had been used in 15
      districts in the city of Nola and 46 surrounding villages by 20 trappers fully
      supported by the program. This is an example of regular active mass screening.
      Systematic treatment of detected cases and well-conducted vector control measures
      give hope to the affected populations to live peacefully in order to contribute
      to the development of their country.

PMID- 21956142
TI  - Diagnosis of paratuberculosis in goats by cell mediated immune response,
      conventional and molecular diagnostic techniques.
AB  - In the present study efficacy of single intradermal Johnin test, acid fast
      staining of faecal smear and IS 900 faecal polymerase chain reaction tests was
      evaluated in 200 goats for detection of Mycobacterium avium subsp
      paratuberculosis. Two hundred goats comprising 150 goats from an organised farm
      in Trichur district and 50 goats reared under field condition at farmers premise
      from Malappuram district of Kerala state formed the study population. Faecal
      smear from all the 200 goats was stained by Ziehl-Neelsen acid fast stain and
      faecal polymerase chain reaction (PCR) specific for M. avium subsp
      paratuberculosis (MAP); IS 900 was performed on all samples. All the animals were
      subjected to single intradermal Johnin test. Out of 200 goats screened for
      paratuberculosis, six goats (3%), 11 goats (5.5%) and 42 goats (21%) were found
      positive by Ziehl-Neelsen acid fast staining of faecal smear, single intradermal
      Johnin test and IS 900 PCR respectively. Results of the present study indicate
      that amplification of IS 900 insertion element was the most specific and
      sensitive diagnostic detection method. Single intradermal Johnin test and Ziehl
      Neelsen acid fast staining did not show any significant difference.

PMID- 21956143
TI  - Human foetal intestinal fibroblasts are hyper-responsive to lipopolysaccharide
      stimulation.
AB  - BACKGROUND: Intestinal myofibroblasts contribute to immune regulation in adults
      with inflammatory bowel disease but have not been characterised in neonatal
      intestinal inflammatory diseases. AIMS: To compare lipopolysaccharide (LPS)
      stimulated interleukin-8 (IL-8) production between human foetal and mature
      intestinal myofibroblasts in vitro. METHODS: Foetal, neonatal and adult cells
      were stimulated with increasing concentrations of E. coli LPS. In LPS stimulated
      foetal myofibroblasts, Toll-like receptor 4 mRNA expression was assessed by real
      time PCR whilst Toll-like receptor 4 receptor activity was determined using anti
      Toll-like receptor 4 antibody. Mitogen activated protein kinase pathway activity
      was assessed using chemical inhibitors and Western blotting. IL-8 production was
      measured by quantitative ELISA. RESULTS: IL-8 production by LPS stimulated foetal
      myofibroblasts occurred in a dose dependent manner. Toll-like receptor 4
      expression was constitutive and Toll-like receptor 4 receptor blockade reduced IL
      8 production by 42% (P=0.0262). C-Jun N-terminal kinase, p38 and NF-kappaB
      inhibitors significantly attenuated LPS stimulated IL-8 production by 42%, 33%
      and 2%, respectively. Mitogen activated protein kinase activity was confirmed by
      the presence of phosphorylated proteins on Western blots. CONCLUSION: These data
      demonstrate increased IL-8 production by foetal myofibroblasts that is partially
      mediated by Toll-like receptor 4, mitogen activated protein kinase and NF-kappaB
      cell signalling pathways. Intestinal myofibroblasts cells may contribute to the
      dysregulated inflammatory response in the immature intestine and may form targets
      that lead to new therapies to prevent neonatal intestinal inflammatory bowel
      diseases.

PMID- 21956144
TI  - Unexpected properties of endostatin-producing mouse BCR-ABL-transformed cells.
AB  - We investigated whether a genetic modification of BCR-ABL-transformed mouse cells
      that resulted in endostatin (ES) production altered their oncogenic potential.
      Mouse B210 cells, which express p210bcr-abl fusion protein and induce leukemia
      like disease and extremely rarely solid tumors after intravenous (i.v.)
      administration, were used. The cells were transfected with a plasmid carrying
      genes for mouse ES and resistance to blasticidine. Transduced cells were isolated
      in media supplemented with blasticidine. Production of ES was determined by
      Western blotting. For further tests, two clones were selected, and their
      pathogenicity after i.v. inoculation was tested. Compared with the parental B210
      cells, the capability of both gene-modified cell clones to induce lethal leukemia
      was reduced. However, mice that did not succumb to leukemia subsequently
      developed solid tumors. They were composed of poorly differentiated cells with
      irregular nuclei and roughly granular chromatin and were well vascularized. FISH
      revealed the presence of the BCR-ABL fusion gene both in tumors and spleens.
      Immunohistological investigation of the tumors demonstrated the production of ES
      in vivo and the cell lines derived from the tumors produced detectable amounts of
      ES, this demonstrating that the formation of solid tumors was not associated with
      the loss or silencing of the ES gene.

PMID- 21956145
TI  - Adipose tissue engineering: three different approaches to seed preadipocytes on a
      collagen-elastin matrix.
AB  - BACKGROUND: Millions of plastic and reconstructive surgical procedures are
      performed each year to repair soft-tissue defects that result from significant
      burns, tumor resections, or congenital defects. Tissue-engineering strategies
      have been investigated to develop methods for generating soft-tissue.
      Preadipocytes represent a promising autologous cell source for adipose tissue
      engineering. These immature precursor cells, which are located between the mature
      adipocytes in the adipose tissue, are much more resistant to mechanical stress
      and ischemic conditions than mature adipocytes. To use preadipocytes for tissue
      engineering purposes, cells were isolated from human adipose tissue and seeded
      onto scaffolds. Once processed, preadipocytes become subject to the human tissue
      act and require handling under much tighter regulations. Therefore, we intended
      to identify any influence caused by processing of preadipocytes prior to seeding
      on the reconstructed adipose tissue formation. MATERIAL AND METHOD: Human
      preadipocytes were isolated from subcutaneous adipose tissue obtained from
      discarded tissue during abdominoplasties of healthy men and women. Preadipocytes
      were divided into 3 groups. Cells of group I were seeded onto the scaffold
      directly after isolation, cells of group II were proliferated for 4 days before
      seeding, and cells of group III were proliferated and induced to differentiate
      before seeded onto the scaffold. A 3-dimensional scaffold (Matriderm, Dr. Otto
      Suwelack Skin and Health Care GmbH, Billerbeck, Germany) containing bovine
      collagen and elastin served as a carrier. Fourteen days after isolation, all
      scaffolds were histologically evaluated, using hematoxylin and eosin, anti-Ki-67
      antibody, as well as immunofluorescence labeling with Pref-1 antibody (DLK (C
      19), peroxisome proliferator-activated receptor gamma antibody, and DAPI (4',6
      diamidino-2-phenylindole). RESULTS: Cells of all groups adhered to the scaffolds
      on day 21 after isolation. Cells of groups I (freshly isolated preadipocytes) and
      II (proliferated preadipocytes) adhered well and penetrated into deeper layers of
      the matrix. In group III (induced preadipocytes), penetration of cells was
      primarily observed to the surface area of the scaffold. DISCUSSION/CONCLUSION: :
      The collagen-elastin matrix serves as a useful scaffold for adipose tissue
      engineering. Freshly isolated preadipocytes as well as proliferated preadipocytes
      showed good penetration into deeper layers of the scaffold, whereas induced
      preadipocytes attached primarily to the surface of the matrix. We conclude that
      there might be different indications for each approach.

PMID- 21956146
TI  - Relationship between the temporal profile of plasma microRNA and left ventricular
      remodeling in patients after myocardial infarction.
AB  - BACKGROUND: microRNAs (miRs) are small noncoding RNAs that recognize and bind to
      mRNAs and inhibit protein translation or degrade mRNA. Studies in animal models
      have suggested that miRs play a translational or posttranslational regulatory
      role in myocardial growth, fibrosis, viability, and remodeling. However, whether
      specific temporal changes in miRs occur in patients during the left ventricular
      (LV) remodeling process that follows a myocardial infarction (post-MI) remains
      unknown. The current pilot study tested the hypotheses that plasma miRs could be
      reliably measured in post-MI patients and that there is a relationship between
      temporal changes in specific miRs and post-MI LV structural remodeling. METHODS
      AND RESULTS: LV end-diastolic volume (echocardiography) and plasma miR were
      measured in age-matched referent controls (CTLs, n=12) and post-MI patients
      (n=12) from day 2 through day 90 post-MI. Selected miRs (miR-1, miR-21, miR-29a,
      miR-133a, and miR-208) were measured using quantitative reverse transcription
      polymerase chain reaction and normalized for endogenous small nuclear RNA U6.
      After MI, LV end-diastolic volume increased progressively compared with CTL; this
      was accompanied by time-dependent changes in specific miRs. For example, miR-21
      initially decreased 2 days post-MI (0.3 +/- 0.1-fold versus CTL; P<0.05),
      increased 5 days post-MI (2 +/- 1-fold versus CTL; P<0.05), and returned to CTL
      values at later post-MI time points. In contrast, miR-29a increased 5 days post
      MI (4 +/- 1-fold versus CTL; P<0.05) and then decreased to CTL at later time
      points. miR-208 increased 5 days post-MI (3 +/- 1-fold versus CTL; P<0.05) and
      remained elevated up to 90 days post-MI. CONCLUSIONS: A time-dependent change in
      miRs occurred in post-MI patients, including an early and robust increase in miRs
      that has affected myocardial growth, fibrosis, and viability. Thus, serially
      profiling miRs in the plasma of post-MI patients may hold both mechanistic and
      prognostic significance.

PMID- 21956148
TI  - Residual DNA analysis in biologics development: review of measurement and
      quantitation technologies and future directions.
AB  - Residual DNA (rDNA) is comprised of deoxyribonucleic acid (DNA) fragments and
      longer length molecules originating from the host organism that may be present in
      samples from recombinant biological processes. Although similar in basic
      structural base pair units, rDNA may exist in different sizes and physical forms.
      Interest in measuring rDNA in recombinant products is based primarily on
      demonstration of effective purification during manufacturing, but also on some
      hypothetical concerns that, in rare cases, depending on the host expression
      system, some DNA sequences may be potentially infectious or oncogenic (e.g., HIV
      virus and the Ras oncogene, respectively). Recent studies suggest that a sequence
      known as long interspersed nucleotide element-1 (LINE-1), widely distributed in
      the mammalian genome, is active as a retrotransposon that can be transcribed to
      RNA, reverse-transcribed into DNA and inserts into a new site in genome. This
      integration process could potentially disrupt critical gene functions or induce
      tumorigenesis in mammals. Genomic DNA from microbial sources, on the other hand,
      could add to risk of immunogenicity to the target recombinant protein being
      expressed, due to the high CpG content and unmethylated DNA sequence. For these
      and other reasons, it is necessary for manufacturers to show clearance of DNA
      throughout production processes and to confirm low levels in the final drug
      substance using an appropriately specific and quantitative analytical method. The
      heterogeneity of potential rDNA sequences that might be makes the testing of all
      potential analytes challenging. The most common methodology for rDNA quantitation
      used currently is real-time polymerase chain reaction (RT-PCR), a robust and
      proven technology. Like most rDNA quantitation methods, the specificity of RT-PCR
      is limited by the sequences to which the primers are directed. To address this,
      primase-based whole genome amplification is introduced herein. This paper will
      review the recent advancement in rDNA quantitation and recent findings regarding
      potential risks of immunogenicity, infectivity, and oncogenicity of rDNA.

PMID- 21956147
TI  - Combination surgery for erectile dysfunction and male incontinence.
AB  - With favorable prognosis, radical therapy for pelvic malignancy no longer is just
      about oncological control, but is important in achieving the trifecta of
      oncological clearance with acceptable sexual function and urinary outcomes. As we
      face the prospect of escalating urogenital dysfunction following our radical
      interventions, we need to carefully assess these functional outcomes and their
      impact on the quality of life of our patients. In men, this includes urinary
      impairments with stress urinary incontinence, various types of voiding
      dysfunction, and sexual impairments (primarily erectile dysfunction and orgasmic
      dysfunction). Based on appropriate clinical and diagnostic assessments of
      severity of adverse outcomes depending on patient preference, combination surgery
      for treatment of erectile dysfunction and stress urinary incontinence is
      effective and durable and has an established, definitive role to address this not
      uncommon problem. This article reviews the prevalence of the problem, the
      available therapeutic options, and evidence of efficacy of these therapies in
      combination.

PMID- 21956149
TI  - High throughput plasma N-glycome profiling using multiplexed labelling and UPLC
      with fluorescence detection.
AB  - A rapid glycomic profiling method is described wherein N-glycans from plasma
      samples individually labelled with aniline, 2-aminobenzamide and 2-aminoacridone
      are mixed, co-injected and separated in the same HILIC-fluorescence run. Transfer
      of the multiplexed method to UPLC-fluorescence permits an increase in sample
      throughput from 24 to 864 plasma samples per day.

PMID- 21956150
TI  - Routine use of diuretics in very-low birth-weight infants in the absence of
      supporting evidence.

PMID- 21956151
TI  - Hyperammonemic coma in an ornithine transcarbamylase mutation carrier following
      antepartum corticosteroids.
AB  - Women who are carriers of the ornithine transcarbamylase (OTC) mutation are at
      risk for developing hyperammonemia during the postpartum period and at times of
      metabolic stress. We present a unique case of hyperammonemic coma occurring in an
      OTC mutation carrier during the antepartum period. Multiple factors, including
      the administration of antenatal corticosteroids, likely precipitated this
      critical condition. Clinicians should be aware of this life-threatening clinical
      presentation and be prepared to identify, treat, and prevent hyperammonemia in
      affected individuals.

PMID- 21956152
TI  - Prenatal ductal thrombosis presenting as cyanotic heart lesion.
AB  - We present a case of a late-preterm infant admitted for suspected cyanotic heart
      disease who was found to have a thrombosed ductus arteriosus. Maternal history
      was significant for heterozygosity for Factor V Leiden, treated with enoxaparin
      during her pregnancy, and congenital hearing loss. The neonate did not have a
      Factor V Leiden mutation detected, but was found to have a heterozygous mutation
      within the MFTHR gene. He was treated with anticoagulation, with improving
      hemodynamics measured by echocardiogram. This case presents a rare disease, which
      is potentially fatal if diagnosis is delayed.

PMID- 21956153
TI  - Properitoneal fat mimicking free air in an infant of a diabetic mother.

PMID- 21956155
TI  - Complete detoxification of tris(1,3-dichloro-2-propyl) phosphate by mixed two
      bacteria, Sphingobium sp. strain TCM1 and Arthrobacter sp. strain PY1.
AB  - Tris(1,3-dichloro-2-propyl) phosphate (TDCPP), a flame retardant, is regarded as
      a potentially toxic and persistent environmental contaminant. We previously
      isolated a TDCPP-degrading bacterium, Sphingobium sp. strain TCM1, which,
      however, produced a toxic metabolite: 1,3-dichloro-2-propanol (1,3-DCP). This
      study was undertaken to develop a technique for complete TDCPP detoxification
      using strain TCM1 with a 1,3-DCP-degrading bacterium, Arthrobacter sp. strain
      PY1. For efficient detoxification, we designed a resting cell system and examined
      the effect of freezing and lyophilization treatments for preparation of their
      resting cells. Results show that treatments had no marked adverse effect on their
      activities. The TDCPP dephosphorylation by TCM1 resting cells was optimal at 30
      degrees C and pH 8.5. Also, 1,3-DCP dehalogenation by strain PY1 resting cells
      was optimal at 35 degrees C and pH 9.5. Under those respective conditions, the
      activities were 2.48 MUmol h-1.OD660-1 for TDCPP and 0.95 MUmol h-1.OD660-1 for
      1,3-DCP. Based on these results, we set the reaction temperature to 30 degrees C
      and pH to 9.0. Then we examined the detoxification of 50 MUM TDCPP using mixed
      resting cells at a final OD(660) of 0.05 for strain TCM1 and 0.2 for strain PY1.
      In these conditions, TDCPP was eliminated after 1h, but some of the resulting 1,3
      DCP remained at a constant level. The increase in strain PY1 cells to a final
      OD660 of 4.0 decreased the TDCPP dephosphorylation rate of strain TCM1 cells but
      achieved complete detoxification of TDCPP during 12 h of reaction.

PMID- 21956154
TI  - Primary cilia and coordination of receptor tyrosine kinase (RTK) signalling.
AB  - Primary cilia are microtubule-based sensory organelles that coordinate signalling
      pathways in cell-cycle control, migration, differentiation and other cellular
      processes critical during development and for tissue homeostasis. Accordingly,
      defects in assembly or function of primary cilia lead to a plethora of
      developmental disorders and pathological conditions now known as ciliopathies. In
      this review, we summarize the current status of the role of primary cilia in
      coordinating receptor tyrosine kinase (RTK) signalling pathways. Further, we
      present potential mechanisms of signalling crosstalk and networking in the
      primary cilium and discuss how defects in ciliary RTK signalling are linked to
      human diseases and disorders.

PMID- 21956156
TI  - When nano meets stem: the impact of nanotechnology in stem cell biology.
AB  - Nanotechnology and biomedical treatments using stem cells are among the latest
      conduits of biotechnological research. Even more recently, scientists have begun
      finding ways to mate these two specialties of science. The advent of
      nanotechnology has paved the way for an explicit understanding of stem cell
      therapy in vivo and by recapitulation of such in vivo environments in the
      culture, this technology seems to accommodate a great potential in providing new
      vistas to stem cell research. Nanotechnology carries in its wake, the development
      of highly stable, efficient and specific gene delivery systems for both in vitro
      and in vivo genetic engineering of stem cells, use of nanoscale systems (such as
      microarrays) for investigation of gene expression in stem cells, creation of
      dynamic three-dimensional nano-environments for in vitro and in vivo maintenance
      and differentiation of stem cells and development of extremely sensitive in vivo
      detection systems to gain insights into the mechanisms of stem cell
      differentiation and apoptosis in different disease models. The present review
      presents an overview of the current applications and future prospects for the use
      of nanotechnology in stem cell biology.

PMID- 21956157
TI  - Characteristics and outcome of immune thrombocytopenia in elderly: results from a
      single center case-controlled study.
AB  - The management of ITP in elderly raises several questions that have not been
      fully addressed in the literature. To assess the impact of ITP in elderly, a case
      control study was performed. The main characteristics at onset and the outcome of
      ITP in 55 patients aged of 70 years and above (cases) were compared with those of
      97 younger adults (controls) seen at the same tertiary referral institution. The
      mean age at diagnosis was respectively 77.8+/-6.1 years (cases) and 40.3+/-14.9
      years (controls). While the median platelet count at time of diagnosis was not
      significantly different in cases and controls (6*10(9) /L, range: 2-26 versus
      12*10(9) /L: 5-21.5), bleeding symptoms were more frequent in cases (82%) than in
      the controls (68%, p=0.07), and the median bleeding score was significantly
      higher in elderly (p=0.001). The rate of treatment-related adverse events was
      more than twofold higher in elderly patients and the mean cumulative duration of
      hospital stay for ITP during the follow-up period was much longer when compared
      to the controls (p<0.0001). Three ITP-related deaths (5.4%) including 1 from
      intracranial hemorrhage occurred in the cases but none in the controls. In
      conclusion, this study confirms that at equivalent platelet count, ITP has a
      greater impact in elderly.

PMID- 21956158
TI  - Anti-carcinogenic properties of omeprazole against human colon cancer cells and
      azoxymethane-induced colonic aberrant crypt foci formation in rats.
AB  - Omeprazole is a proton pump inhibitor, a widely used drug to treat ulcers and
      gastroesophageal refluxdisease. We have evaluated colon cancer chemopreventive
      properties of omeprazole using azoxymethane (AOM)-induced colonic aberrant crypt
      foci (ACF) in male F344 rats and analyzed cell growth inhibition and apoptosis
      induction in human colon cancer cells. Five-week-old male F344 rats were fed a
      control or experimental diet containing two doses of omeprazole (200 and 400
      ppm). After one week, all animals were s.c. injected with AOM (15 mg/kg body
      weight, once weekly for two weeks). Rats continued on experimental diets for
      seven more weeks before being sacrificed. Colons were histopathologically
      evaluated for ACF. Human colon cancer HCT-116 and HCA-7 cells treated with
      omeprazole were evaluated for different markers associated with proliferation and
      apoptotic markers using Western blot technique. Rats fed with 200 and 400 ppm of
      omeprazole significantly suppressed total colonic ACF formation (~30%, P<0.001)
      and showed significant suppression of multi-crypt foci (~30-50%, P<0.05-0.001).
      Omeprazole produced significant dose-response effects on inhibition of multi
      crypt foci (>=4). Omeprazole treatment in human colon cancer cell lines HCT-116
      and HCA-7 cells resulted in induction of p21waf1/cip1 and decreased the
      expression of anti-apoptotic proteins Bcl-2, Bcl-XL and survivin in a dose
      dependent manner. Anticancer properties observed in colon cancer cell lines
      suggest that omeprazole may induce key signaling molecules of antiproliferation
      and inhibition of anti-apoptotic proteins.

PMID- 21956159
TI  - Temporary catheter first perfusion during hand replantation with prolonged warm
      ischaemia.
AB  - INTRODUCTION: Since the first successful arm replantation reported by Malt and
      McKhann in 1962, developments and refinements to upper extremity replantation
      techniques have led to higher success rates with better functional outcomes. One
      of the most important determinants of a successful macroreplantation is the
      ischaemic time of the amputated part, as irreversible muscle necrosis begins
      after 6 hours of warm ischaemia. With major trauma and plastic surgery units
      usually covering a wide geographical area, it is often difficult to ensure
      patient injury to revascularization time is less than 6 hours. In 1981, Nunley et
      al described the temporary catheter perfusion technique in upper limb
      replantation surgery to reduce ischaemia time without any significant
      complications. When used in appropriate cases this technique can reduce
      complication rates in upper limb replantation surgeries. MATERIAL AND METHODS:
      Temporary catheter first perfusion was used in a hand replantation after 6 hours
      of warm ischaemia, with preservation of the intrinsic muscles, as evidenced by
      return of function. The technique used is described, along with relevant
      literature. RESULTS: Temporary catheter perfusion allowed early reperfusion of
      the amputated hand, improving the chance of intrinsic muscle preservation despite
      delayed presentation. It allowed better wound evaluation and debridement, and
      facilitated better bone stabilisation prior to vascular repair. CONCLUSION:
      Temporary catheter perfusion is well described in proximal upper limb
      replantation procedures. This case shows that it is also a useful adjunct for
      hand replantation, particularly when the patient presents with a critical
      duration of warm ischaemia.

PMID- 21956160
TI  - Animal models of ricin toxicosis.
AB  - Animal models of ricin toxicosis are necessary for testing the efficacy of
      therapeutic measures, as well studying the mechanisms by which ricin exerts its
      toxicity in intact animals. Because ricin can serve as a particularly well
      characterized model of tissue damage, and the host response to that damage,
      studies of the mechanisms of ricin toxicity may have more general applicability.
      For example, our studies of the molecular mechanisms underlying the development
      of ricin-induced hypoglycemia may help elucidate the relationship of type II
      diabetes, insulin resistance, and inflammation. Studies in non-human primates are
      most relevant for testing and developing agents having clinical utility. But
      these animals are expensive and limited in quantity, and so rodents are used for
      most mechanistic studies.

PMID- 21956161
TI  - The Toxicology Investigators Consortium (ToxIC) Registry.
AB  - Many medical toxicologists are interested in participating in a practice-based,
      multicenter research and toxicosurveillance network. In 2009, the American
      College of Medical Toxicology established the Toxicology Investigators Consortium
      (ToxIC). One facet of ToxIC is a registry that can be used for surveillance of
      new or old agents, assessment of treatment decisions, and the creation of new
      research questions. This paper describes the development of and the initial
      experiences with this registry of toxicology patients. In November 2009, ACMT
      invited members to participate in a new registry of cases evaluated and cared for
      by practicing medical toxicologists who provide direct hands-on clinical care. A
      password-protected, encrypted, online registry data site was created to upload a
      newly developed electronic case report form (CRF) on registry patients. The CRF
      includes demographics; encounter circumstances; agent; syndrome, symptoms, and
      signs; and treatment. A test version at four sites began in January 2010, seven
      additional sites were added in March 2010 for the beta phase, and the registry
      was opened to all interested US medical toxicology practices in April 2010. The
      CRF underwent continuous modifications based upon frequent feedback from and
      discussion among the participants. Thirty-three toxicology practice sites,
      encompassing 56 hospitals and clinics, have entered data into the ToxIC Registry.
      During the first 14 months of data collection, 5,412 patients were entered. The
      experience thus far demonstrates that the creation of this registry is feasible
      and constitutes a potentially powerful toxicosurveillance and robust research
      tool.

PMID- 21956162
TI  - Conditional transgenic expression of TIR-domain-containing adaptor-inducing
      interferon-beta (TRIF) in the adult mouse heart is protective in acute viral
      myocarditis.
AB  - TIR-domain-containing adaptor-inducing interferon-beta (TRIF) plays a major role
      in Toll-like receptor 3 (TLR3) mediated signaling. Mice deficient in TLR3 and
      TRIF have been shown to be highly susceptible to enterovirus-induced myocardial
      injury. These mice have decreased production of antiviral cytokines and increased
      viral replication in the heart. Therefore, we hypothesized that conditional
      overexpression of TRIF would change cardiac myocyte susceptibility to virus
      infection by augmenting the antiviral response. We generated double-transgenic
      MHC-tTA/MHC(tetO)-TRIF mice (DT), with conditional cardiac-specific
      overexpression of TRIF. Naive DT mice had increased cardiac expression of
      antiviral cytokines and increased cellular infiltration but no alterations in
      cardiac function. DT mice were less susceptible to encephalomyocarditis virus
      (EMCV) infection and had a significantly lower viral load in the heart when
      compared to littermate (LM) and MHC(tetO)-TRIF (ST) mice. Histopathological
      examination showed that the severity of myocarditis was also attenuated in DT
      mice. Furthermore, the decreased virus titers in the DT mouse hearts led to less
      cardiac damage and better cardiac function when compared to LM and ST mice.
      Administration of doxycycline to DT mice suppressed the protective effects of
      TRIF overexpression in the heart. The findings of the present study establish the
      importance of cardiac-specific TRIF-mediated signaling in the heart in acute
      viral myocarditis and identify potentially important targets for diagnostic and
      therapeutic strategies.

PMID- 21956163
TI  - Effect of chronic alcohol exposure on folate uptake by liver mitochondria.
AB  - Mammalian cells obtain folate, a water-soluble vitamin, from their surroundings
      via transport across cell membrane. Intracellular folate is compartmentalized
      between the cytoplasm and the mitochondria. Transport of folate from the
      cytoplasm into the mitochondria is via a specific carrier-mediated process
      involving the mitochondrial folate transporter (MFT). Chronic alcohol use
      negatively impacts folate homeostasis, but its effect on mitochondrial folate
      uptake is not clear. We addressed this issue using mitochondrial preparations
      isolated from the liver of rats chronically fed an alcohol liquid diet and from
      human liver HepG2 cells chronically exposed to alcohol. The results showed that
      chronic alcohol feeding of rats leads to a significant inhibition in
      mitochondrial carrier-mediated folate uptake. This inhibition was associated with
      a significant reduction in the level of expression of the MFT protein, mRNA, and
      heterogenous nuclear RNA (hnRNA). Similarly, chronic alcohol exposure (96 h) of
      HepG2 cells led to significant inhibition in mitochondrial carrier-mediated
      folate uptake, which was associated with a marked reduction in the level of
      expression of the human MFT (hMFT). To determine whether the latter effect is, in
      part, being exerted at the transcriptional level, we cloned the 5'-regulatory
      region of the human SLC25A32 gene (which encodes the hMFT) and showed that
      chronic alcohol exposure of HepG2 cells leads to a significant inhibition in its
      promoter activity. These studies show for the first time that chronic alcohol
      feeding/exposure leads to a significant inhibition in mitochondrial carrier
      mediated folate uptake and that the inhibition is, in part, being exerted at the
      level of transcription of the SLC25A32 gene.

PMID- 21956164
TI  - Chloride channel ClC-2 modulates tight junction barrier function via
      intracellular trafficking of occludin.
AB  - Previously, we have demonstrated that the chloride channel ClC-2 modulates
      intestinal mucosal barrier function. In the present study, we investigated the
      role of ClC-2 in epithelial barrier development and maintenance in Caco-2 cells.
      During early monolayer formation, silencing of ClC-2 with small interfering
      (si)RNA led to a significant delay in the development of transepithelial
      resistance (TER) and disruption of occludin localization. Proteomic analysis
      employing liquid chromatography-mass spectrometry /mass spectrometry revealed
      association of ClC-2 with key proteins involved in intracellular trafficking,
      including caveolin-1 and Rab5. In ClC-2 siRNA-treated cells, occludin
      colocalization with caveolin-1 was diffuse and in the subapical region.
      Subapically distributed occludin in ClC-2 siRNA-treated cells showed marked
      colocalization with Rab5. To study the link between ClC-2 and trafficking of
      occludin in confluent epithelial monolayers, a Caco-2 cell clone expressing ClC-2
      short hairpin (sh)RNA was established. Disruption of caveolae with methyl-beta
      cyclodextrin (MbetaCD) caused a marked drop in TER and profound redistribution of
      caveolin-1-occludin coimmunofluorescence in ClC-2 shRNA cells. In ClC-2 shRNA
      cells, focal aggregations of Rab5-occludin coimmunofluorescence were present
      within the cytoplasm. Wortmannin caused an acute fall in TER in ClC-2 shRNA cells
      and subapical, diffuse redistribution of Rab5-occludin coimmunofluorescence in
      ClC-2 shRNA cells. An endocytosis and recycling assay for occludin revealed
      higher basal rate of endocytosis of occludin in ClC-2 shRNA cells. Wortmannin
      significantly reduced the rate of recycling of occludin in ClC-2 shRNA cells.
      These data clearly indicate that ClC-2 plays an important role in the modulation
      of tight junctions by influencing caveolar trafficking of the tight junction
      protein occludin.

PMID- 21956165
TI  - NHLBI-AbDesigner: an online tool for design of peptide-directed antibodies.
AB  - Investigation of physiological mechanisms at a cellular level often requires
      production of high-quality antibodies, frequently using synthetic peptides as
      immunogens. Here we describe a new, web-based software tool called NHLBI
      AbDesigner that allows the user to visualize the information needed to choose
      optimal peptide sequences for peptide-directed antibody production
      (http://helixweb.nih.gov/AbDesigner/). The choice of an immunizing peptide is
      generally based on a need to optimize immunogenicity, antibody specificity,
      multispecies conservation, and robustness in the face of posttranslational
      modifications (PTMs). AbDesigner displays information relevant to these criteria
      as follows: 1) "Immunogenicity Score," based on hydropathy and secondary
      structure prediction; 2) "Uniqueness Score," a predictor of specificity of an
      antibody against all proteins expressed in the same species; 3) "Conservation
      Score," a predictor of ability of the antibody to recognize orthologs in other
      animal species; and 4) "Protein Features" that show structural domains, variable
      regions, and annotated PTMs that may affect antibody performance. AbDesigner
      displays the information online in an interactive graphical user interface, which
      allows the user to recognize the trade-offs that exist for alternative synthetic
      peptide choices and to choose the one that is best for a proposed application.
      Several examples of the use of AbDesigner for the display of such trade-offs are
      presented, including production of a new antibody to Slc9a3. We also used the
      program in large-scale mode to create a database listing the 15-amino acid
      peptides with the highest Immunogenicity Scores for all known proteins in five
      animal species, one plant species (Arabidopsis thaliana), and Saccharomyces
      cerevisiae.

PMID- 21956167
TI  - Targeting therapeutic effects: subcellular location matters. Focus on
      "Pharmacological AMP-kinase activators have compartment-specific effects on cell
      physiology".

PMID- 21956166
TI  - Cholinergic signaling inhibits oxalate transport by human intestinal T84 cells.
AB  - Urolithiasis remains a very common disease in Western countries. Seventy to
      eighty percent of kidney stones are composed of calcium oxalate, and minor
      changes in urinary oxalate affect stone risk. Intestinal oxalate secretion
      mediated by anion exchanger SLC26A6 plays a major constitutive role in limiting
      net absorption of ingested oxalate, thereby preventing hyperoxaluria and calcium
      oxalate urolithiasis. Using the relatively selective PKC-delta inhibitor
      rottlerin, we had previously found that PKC-delta activation inhibits Slc26a6
      activity in mouse duodenal tissue. To identify a model system to study
      physiologic agonists upstream of PKC-delta, we characterized the human intestinal
      cell line T84. Knockdown studies demonstrated that endogenous SLC26A6 mediates
      most of the oxalate transport by T84 cells. Cholinergic stimulation with
      carbachol modulates intestinal ion transport through signaling pathways including
      PKC activation. We therefore examined whether carbachol affects oxalate transport
      in T84 cells. We found that carbachol significantly inhibited oxalate transport
      by T84 cells, an effect blocked by rottlerin. Carbachol also led to significant
      translocation of PKC-delta from the cytosol to the membrane of T84 cells. Using
      pharmacological inhibitors, we observed that carbachol inhibits oxalate transport
      through the M(3) muscarinic receptor and phospholipase C. Utilizing the Src
      inhibitor PP2 and phosphorylation studies, we found that the observed regulation
      downstream of PKC-delta is partially mediated by c-Src. Biotinylation studies
      revealed that carbachol inhibits oxalate transport by reducing SLC26A6 surface
      expression. We conclude that carbachol negatively regulates oxalate transport by
      reducing SLC26A6 surface expression in T84 cells through signaling pathways
      including the M(3) muscarinic receptor, phospholipase C, PKC-delta, and c-Src.

PMID- 21956168
TI  - Finasteride for treatment of refractory hemospermia: prospective placebo
      controlled study.
AB  - OBJECTIVE: Finasteride had been used to control frequent hematuria due to BPH. In
      this study, we tried to test the efficacy of finasteride to control refractory
      idiopathic hemospermia lasting for more than 3 months for which conservative
      treatment has failed. PATIENTS AND METHODS: In a period from 1998 to 2008, 70
      patients with hemospermia presented to urology department, Sohag university
      hospital. Only 24 patients were diagnosed as having refractory hemospermia of
      idiopathic nature. They were divided and randomized into two equal groups, 12
      patients each. One group received finasteride 5 mg daily for 3 months, and the
      second group received placebo. Patients were followed at monthly intervals both
      subjectively and objectively by semen analysis and TRUS for three successive
      months and after 1 year. RESULTS: In the finasteride-treated group, 8 patients
      (66.7%) have demonstrated a remission of the episodes of their hemospermia
      symptom within 2-5 weeks after the start of treatment. We confirmed this
      subjective improvement by repeated semen analysis. Patients continued treatment
      for 3 months without recurrence of bleeding. On the other hand, only three
      patients (25%) in placebo group mentioned the disappearance of their symptom
      after a period of 1-2 months on treatment. On semen analysis, those three
      patients showed considerable number of RBCs (>50/HPF). CONCLUSION: Finasteride
      could be safely used as a treatment for patients with idiopathic refractory
      hemospermia after exclusion of the other organic causes. However, our results are
      preliminary, and larger series with longer follow-up are required to confirm the
      results.

PMID- 21956169
TI  - Development and validation of a generic fluorescent methyltransferase activity
      assay based on the transcreener AMP/GMP assay.
AB  - Methylation is a ubiquitous covalent modification used to control the function of
      diverse biomolecules including hormones, neurotransmitters, xenobiotics,
      proteins, nucleic acids, and lipids. Histone methyltransferases (HMTs) are
      currently of high interest as drug targets because of their role in epigenetic
      regulation; however, most HMT assay methods are either not amenable to a high
      throughput screening (HTS) environment or are applicable to a limited number of
      enzymes. The authors developed a generic methyltransferase assay method using
      fluorescent immunodetection of adenosine monophosphate (AMP), which is formed
      from the MT reaction product S-adenosylhomocysteine in a dual-enzyme coupling
      step. The detection range of the assay; its suitability for HTS, including
      stability of reagents following dispensing and after addition to reactions; and
      the potential for interference from drug-like molecules was investigated. In
      addition, the use of the assay for measuring inhibitor potencies with peptide or
      intact protein substrates was examined through pilot screening with selected
      reference enzymes including HMT G9a. By combining a novel enzymatic coupling step
      with the well-characterized Transcreener AMP/GMP assay, the authors have
      developed a robust HTS assay for HMTs that should be broadly applicable to other
      types of methyltransferases as well.

PMID- 21956170
TI  - Workflow and metrics for image quality control in large-scale high-content
      screens.
AB  - Automated microscopes have enabled the unprecedented collection of images at a
      rate that precludes visual inspection. Automated image analysis is required to
      identify interesting samples and extract quantitative information for high
      content screening (HCS). However, researchers are impeded by the lack of metrics
      and software tools to identify image-based aberrations that pollute data,
      limiting experiment quality. The authors have developed and validated approaches
      to identify those image acquisition artifacts that prevent optimal extraction of
      knowledge from high-content microscopy experiments. They have implemented these
      as a versatile, open-source toolbox of algorithms and metrics readily usable by
      biologists to improve data quality in a wide variety of biological experiments.

PMID- 21956171
TI  - Knockdown of ubiquitin ligases in glioblastoma cancer stem cells leads to cell
      death and differentiation.
AB  - The cancer stem cell (CSC) hypothesis proposes that a subpopulation of CSCs is
      frequently responsible for chemotherapy resistance and metastasis and is now a
      point of attack for research into the next generation of therapeutics. Although
      many of these agents are directed at inducing CSC apoptosis (as well as the bulk
      tumor), some agents may also decrease cell "stemness" possibly through induction
      of differentiation. Ubiquitin ligases, critical to virtually all cellular
      signaling systems, alter the degradation or trafficking of most proteins in the
      cell, and indeed broad perturbation of this system, through inhibition of the
      proteosome, is a successful cancer treatment. The authors examined several
      glioblastoma stem cell isolates pre- and postdifferentiation to elucidate the
      phenotypic effects following shRNA knockdown of ubiquitin ligases. The results
      were analyzed using high-content imaging (HCI) and identified ubiquitin ligases
      capable of inducing both CSC differentiation and apoptosis. Quite often these
      effects were specific to CSCs, as ubiquitin ligase knockdown in terminally
      differentiated progeny yielded markedly different results. The resolution of HCI
      at the subpopulation level makes it an excellent tool for the analysis of CSC
      phenotypic changes induced by shRNA knockdown and may suggest additional methods
      to target these cells for death or differentiation.

PMID- 21956172
TI  - Virtual screening against acetylcholine binding protein.
AB  - The nicotinic acetylcholine receptors (nAChRs) are a member of the ligand-gated
      ion channel family and play a key role in the transfer of information across
      neurological networks. The X-ray crystal structure of agonist-bound alpha(7)
      acetylcholine binding protein (AChBP) has been recognized as the most appropriate
      template to model the ligand-binding domain of nAChR for studying the molecular
      mechanism of the receptor-ligand interactions. Virtual screening of the National
      Cancer Institute diversity set, a library of 1990 compounds with nonredundant
      pharmacophore profiles, using AutoDock against AChBPs revealed 51 potential
      candidates. In vitro radioligand competition assays using [(3)H] epibatidine
      against the AChBPs from the freshwater snails, Lymnaea stagnalis, and from the
      marine species, Aplysia californica and the mutant (AcY55W), revealed seven
      compounds from the list of candidates that had micromolar to nanomolar affinities
      for the AChBPs. Further investigation on alpha(7)nAChR expressing in Xenopus
      oocytes and on the recombinant receptors with fluorescence resonance energy
      transfer (FRET)-based calcium sensor expressing in HEK cells showed that seven
      compounds were antagonists of alpha(7)nAChR, only one compound (NSC34352)
      demonstrated partial agonistic effect at low dose (10 uM), and two compounds
      (NSC36369 and NSC34352) were selective antagonists on alpha(7)nAchR with moderate
      potency. These hits serve as novel templates/scaffolds for development of more
      potent and specific in the AChR systems.

PMID- 21956173
TI  - Development of methods for quantitative comparison of pooled shRNAs by mass
      sequencing.
AB  - Pooled short-hairpin RNA (shRNA) library screening is a powerful tool for
      identifying a set of genes in biological pathways that require stable expression
      to produce a desired phenotype. Massive parallel sequencing of half-hairpins has
      proven highly variable and has not given satisfactory results concerning the
      relative abundance of different shRNAs before and after selection. Here, the
      authors describe a method for quantitative comparison of half-hairpins from
      pooled shRNAs in the mir30-based pGIPZ vector that is analyzed by massive
      parallel sequencing. Introducing a multiplexing code and refining the sample
      preparation scheme resulted in the predicted ability to detect twofold
      enrichments. These improvements should permit half-hairpin sequencing to analyze
      either dropout screens or selective pooled shRNA screens of limited stringency to
      analyze phenotypes not accessible in transient experiments.

PMID- 21956174
TI  - Resorufin butyrate as a soluble and monomeric high-throughput substrate for a
      triglyceride lipase.
AB  - Triglyceride lipases such as lipoprotein lipase, endothelial lipase, and hepatic
      lipase play key roles in controlling the levels of plasma lipoprotein.
      Accordingly, small-molecule modulation of these species could alter patient lipid
      profiles with corresponding health effects. Screening of these enzymes for small
      molecule therapeutics has historically involved the use of lipid-based particles
      to mimic native substrates. However, particle-based artifacts can complicate the
      discovery of therapeutic molecules. As a simplifying solution, the authors sought
      to develop an approach involving a soluble and monomeric lipase substrate. Using
      purified bovine lipoprotein lipase as a model system, they show that the
      hydrolysis of resorufin butyrate can be fluorescently monitored to give a robust
      assay (Z' > 0.8). Critically, using parallel approaches, they show that resorufin
      butyrate is soluble and monomeric under assay conditions. The presented assay
      should be useful as a simple and inexpensive primary or secondary screen for the
      discovery of therapeutic lipase modulators.

PMID- 21956175
TI  - Progress in the discovery of small-molecule inhibitors of bromodomain--histone
      interactions.
AB  - Bromodomains are structurally conserved protein modules present in a large number
      of chromatin-associated proteins and in many nuclear histone acetyltransferases.
      The bromodomain functions as an acetyl-lysine binding domain and has been shown
      to be pivotal in regulating protein-protein interactions in chromatin-mediated
      cellular gene transcription, cell proliferation, and viral transcriptional
      activation. Structural analyses of these modules in complex with acetyl-lysine
      peptide ligands provide insights into the molecular basis for recognition and
      ligand selectivity within this epigenetic reader family. However, there are
      significant challenges in configuring assays to identify inhibitors of these
      proteins. This review focuses on the progress made in developing methods to
      identify peptidic and small-molecule ligands using biophysical label-free and
      biochemical approaches. The advantage of each technique and the results reported
      are summarized, highlighting the potential applicably to other reader domains and
      the caveats in translation from simple in vitro systems to a biological context.

PMID- 21956176
TI  - Radiologic case study.

PMID- 21956177
TI  - Inside-out health care reform.

PMID- 21956178
TI  - Novel venting technique for intramedullary rod fixation of pathologic fractures.
AB  - This article introduces a novel technique to vent the femur and potentially
      decrease the embolic load created by reaming during intramedullary rod fixation
      of impending pathologic femur fractures. We used readily available operating room
      equipment to create a distal femoral vent hole without interfering with standard
      intramedullary instrumentation and with minimal increase in surgical time. This
      technique can be used for the prophylactic intramedullary stabilization of
      impending pathologic femur fractures from metabolic bone disease, metastatic
      cancer, and bisphosphonate use.

PMID- 21956179
TI  - Anterior ankle impingement.

PMID- 21956180
TI  - Periosteal avulsion of the posterolateral corner of the knee in an adolescent: an
      unreported case.
AB  - Isolated injuries of the posterolateral corner of the knee are uncommon injuries
      in adults and are relatively unheard of in the pediatric population. This article
      reports a case of a 13-year-old boy who sustained an external rotation injury to
      his proximal tibia on a slightly flexed knee while playing football. Radiographs
      showed an avulsed fragment from the lateral femoral condyle. A magnetic resonance
      image was read as an avulsion of the femoral insertion of the lateral collateral
      ligament with associated bone bruise of the lateral femoral condyle. At
      operation, the fragment consisted of the femoral insertion of the popliteus
      tendon and the lateral collateral ligament, which was anatomically reduced and
      internally fixed with a screw and soft tissue washer. Six weeks postoperatively,
      the patient had full range of motion. To our knowledge, this injury has not been
      reported in the pediatric population.

PMID- 21956181
TI  - Novel oral anticoagulants for VTE prevention in orthopedic surgery: overview of
      phase 3 trials.
AB  - Outpatient use of anticoagulants to prevent venous thromboembolism after total
      hip or knee arthroplasty may be hampered either by requirements for parenteral
      administration or high variability and frequent monitoring of anticoagulant
      activity. Trials of the new oral direct factor Xa inhibitors rivaroxaban and
      apixaban and the direct thrombin inhibitor dabigatran indicate that they can be
      administered in fixed doses without monitoring and that they generally have
      efficacy at least equivalent to enoxaparin, although with potential minor
      differences in the balance of efficacy vs risk for bleeding. This article reviews
      the results and pharmacokinetic properties that may influence their use in
      clinical practice.

PMID- 21956183
TI  - A simple and economical route to generate functional hepatocyte-like cells from
      hESCs and their application in evaluating alcohol induced liver damage.
AB  - The in vitro derived hepatocytes from human embryonic stem cells (hESC) is a
      promising tool to acquire improved knowledge of the cellular and molecular events
      underlying early human liver development under physiological and pathological
      conditions. Here we report a simple two-step protocol employing conditioned
      medium (CM) from human hepatocellular carcinoma cell line, HepG2 to generate
      functional hepatocyte-like cells from hESC. Immunocytochemistry, flow cytometry,
      quantitative RT-PCR, and biochemical analyses revealed that the endodermal
      progenitors appeared as pockets in culture, and the cascade of genes associated
      with the formation of definitive endoderm (HNF-3beta, SOX-17, DLX-5, CXCR4) was
      consistent and in concurrence with the up-regulation of the markers for hepatic
      progenitors [alpha-feto protein (AFP), HNF-4alpha, CK-19, albumin, alpha-1
      antitrypsin (AAT)], followed by maturation into functional hepatocytes [tyrosine
      transferase (TAT), tryptophan-2, 3-dioxygenase (TDO), glucose 6-phosphate (G6P),
      CYP3A4, CYP7A1]. We witnessed that the gene expression profile during this
      differentiation process recapitulated in vivo liver development demonstrating a
      gradual down-regulation of extra embryonic endodermal markers (SOX-7, HNF-1beta,
      SNAIL-1, LAMININ-1, CDX2), and the generated hepatic cells performed multiple
      liver functions. Since prenatal alcohol exposure is known to provoke irreversible
      abnormalities in the fetal cells and developing tissues, we exposed in vitro
      generated hepatocytes to ethanol (EtOH) and found that EtOH treatment not only
      impairs the survival and proliferation, but also induces apoptosis and perturbs
      differentiation of progenitor cells into hepatocytes. This disruption was
      accompanied by alterations in the expression of genes and proteins involved in
      hepatogenesis. Our results provide new insights into the wider range of
      destruction caused by alcohol on the dynamic process of liver organogenesis.

PMID- 21956184
TI  - Evolving treatment strategies for management of cardiorenal syndrome.
AB  - OPINION STATEMENT: The treatment of acute decompensated heart failure in the
      presence of progressive renal dysfunction is a commonly encountered dilemma in
      clinical practice. Also known as cardiorenal syndrome, this complex disease state
      has forced researchers and clinicians to develop new treatment strategies to
      relieve the symptomatic congestion of heart failure while preserving renal
      function. Loop diuretics remain the standard of pharmacologic treatment of acute
      heart failure, but their effects on renal function have been called into
      question. The DOSE trial set out to determine optimal diuretic dosing strategies
      but no clear regimen was firmly established. Initial studies with vasopressin
      antagonists showed promise in their ability to increase urine output, provide
      short-term symptom relief, and correct hyponatremia while maintaining renal
      function. Unfortunately, the EVEREST trial did not demonstrate any benefit on
      long-term clinical outcomes. Adenosine antagonists also appeared to be an
      emerging therapeutic option, but the recently completed PROTECT trial failed to
      establish their role in the treatment of cardiorenal syndrome. Both nesiritide
      and low-dose dopamine have endured years of trials with mixed results. Most
      recently, findings from the ASCEND-HF trial showed that nesiritide was safe with
      no adverse effects on renal function or mortality and was associated with a
      modest improvement in dyspnea. The ongoing ROSE study, sponsored by the National
      Institutes of Health Heart Failure Research Network, will attempt to confirm the
      safety and efficacy profiles of low-dose nesiritide and dopamine, as well as
      clarify their roles within acute heart failure management. Despite its inherent
      complexities, ultrafiltration has demonstrated potential benefit in several
      clinical outcomes compared to traditional pharmacotherapy. The results of the
      CARRESS-HF trial will reveal how the use of ultrafiltration specifically applies
      to patients with cardiorenal syndrome. The most exciting aspects about our
      evolving understanding of the cardiorenal system are the innovative treatments
      that have emerged as a result. The creation of chimeric natriuretic peptides,
      targeted intra-renal pharmacotherapy, the novel use of phosphodiesterase
      inhibitors, and combination treatment strategies demonstrate that despite our
      varied success in treating cardiorenal syndrome in the past, there are highly
      encouraging translational therapies rapidly developing in the pipeline.

PMID- 21956186
TI  - Solvothermal synthesis, crystal structure, and properties of lanthanide-organic
      frameworks based on thiophene-2,5-dicarboxylic acid.
AB  - A series of lanthanide-organic framework coordination polymers,
      {[La(2)(TDC)(2)(NO(3))(H(2)O)(4)](OH).5H(2)O}(n) (1) and
      [Ln(TDC)(NO(3))(H(2)O)](n) (TDC = thiophene- 2, 5- dicarboxylic acid; Ln = Nd(2),
      Sm(3), Eu(4), Gd(5), Tb(6), Dy(7), Ho(8), Er(9), Yb(10)) have been synthesized by
      solvothermal reaction and characterized by elemental analysis, FT-IR, TG
      analysis, single-crystal X-ray diffraction and power X-ray diffraction. The
      single-crystal X-ray diffraction analysis results show that 1 displays a 3-D
      porous framework with (3,7)-connected {4(10).6(11)}{4(3)} topology. The compounds
      2-10 crystallized in the same P2(1)/c space group and exhibits a (3,6)-connected
      {4.6(2)}(2){4(2).6(10).8(3)} topology, Right-handed and left-handed helical
      chains coexist in the 2-D layer structure. The luminescence properties of 2-10
      and the magnetic properties of 5,7,8,9 were investigated.

PMID- 21956187
TI  - Nephrocalcinosis and urolithiasis in children.
AB  - The incidence of adult urolithiasis has increased significantly in industrialized
      countries over the past decades. Sound incidence rates are not available for
      children, nor are they known for nephrocalcinosis, which can appear as a single
      entity or together with urolithiasis. In contrast to the adult kidney stone
      patient, where environmental factors are the main cause, genetic and/or metabolic
      disorders are the main reason for childhood nephrocalcinosis and urolithiasis.
      While hypercalciuria is considered to be the most frequent risk factor, several
      other metabolic disorders such as hypocitraturia or hyperoxaluria, as well as a
      variety of renal tubular diseases, e.g., Dent's disease or renal tubular
      acidosis, have to be ruled out by urine and/or blood analysis. Associated
      symptoms such as growth retardation, intestinal absorption, or bone
      demineralization should be evaluated for diagnostic and therapeutic purposes.
      Preterm infants are a special risk population with a high incidence of
      nephrocalcinosis arising from immature kidney, medication, and hypocitraturia. In
      children, concise evaluation will reveal an underlying pathomechanism in >75% of
      patients. Early treatment reducing urinary saturation of the soluble by
      increasing fluid intake and by providing crystallization inhibitors, as well as
      disease-specific medication, are mandatory to prevent recurrent kidney stones
      and/or progressive nephrocalcinosis, and consequently deterioration of renal
      function.

PMID- 21956185
TI  - Rare coding variants in ALPL are associated with low serum alkaline phosphatase
      and low bone mineral density.
AB  - Alkaline phosphatase (ALP) plays an essential role in the regulation of tissue
      mineralization, and its activity is highly heritable. Guided by genetic
      associations discovered in a murine model, we hypothesized a role for rare coding
      variants in determining serum ALP level and bone mineral density (BMD) in humans.
      We sequenced the coding regions of the ALP gene (ALPL) in men with low and normal
      serum ALP activity levels. Single-nucleotide ALPL variants, including 19 rare
      nonsynonymous variants (minor allele frequency <1%), were much more frequent
      among the low ALP group (33.8%) than the normal group (1.4%, p = 1 * 10(-11)).
      Within the low ALP group, men with a rare, nonsynonymous variant had 11.2% lower
      mean serum ALP (p = 3.9 * 10(-4)), 6.7% lower BMD (p = 0.03), and 11.1% higher
      serum phosphate (p = 0.002) than those without. In contrast, common nonsynonymous
      variants had no association with serum ALP, phosphate, or BMD. Multiple rare ALPL
      coding variants are present in the general population, and nonsynonymous coding
      variants may be responsible for heritable differences in mineralization and thus
      BMD.

PMID- 21956188
TI  - Should we screen for coronary artery disease in asymptomatic chronic dialysis
      patients?
AB  - The hemodialysis population is characterized by a high prevalence of
      'asymptomatic' coronary artery disease (CAD), which should be interpreted
      differently from asymptomatic disease in the general population. A
      hemodynamically significant stenosis may not become clinically apparent owing to
      impaired exercise tolerance and autonomic neuropathy. The continuous presence of
      silent ischemia may cause heart failure, arrhythmias, and sudden death. Whether
      revascularization of an asymptomatic dialysis patient improves outcome remains a
      moot point, although several observational studies and one small RCT suggest a
      benefit. It can therefore be defended to screen asymptomatic dialysis patients
      for CAD. A number of noninvasive screening tests are available, but none has
      proved equally practical and reliable in the dialysis population as in the
      general population. Myocardial perfusion scintigraphy (MPS) before and after a
      pharmacological stress such as dipyridamole can reveal both ischemia and
      myocardial scarring. When compared with coronary angiography, low sensitivities
      were reported and attributed to impaired vasodilation to dipyridamole in dialysis
      patients. A more likely explanation is that not every anatomical stenosis will
      lead to impaired coronary blood flow on MPS. Numerous studies have shown an
      incremental prognostic value of dipyridamole-MPS over clinical data for
      prediction of adverse cardiac events, in some studies even over coronary
      angiography. Pending the availability of high-quality evidence, in our opinion
      asymptomatic dialysis patients could undergo dipyridamole-MPS, followed by
      coronary angiography in case of an abnormal scan. This combined physiological and
      anatomical evaluation of the coronary circulation allows us to determine which
      coronary stenosis is clinically relevant and therefore should be revascularized.

PMID- 21956189
TI  - Association between prehypertension and chronic kidney disease in the Japanese
      general population.
AB  - The increased prevalence of chronic kidney disease (CKD) is a consequence of the
      accumulation of risk factors, one of which is hypertension. Here we assessed the
      prevalence of CKD according to blood pressure among 232,025 patients in a
      Japanese nationwide database with a focus on the prevalence and risk factors of
      CKD in prehypertension. Patients were stratified by blood pressure and included
      75,474 with optimal blood pressure (less than 120/80 mm Hg); 59,194 with
      prehypertension and a normal blood pressure (120-129/80-84 mm Hg) or 46,547
      patients with high-normal blood pressure (130-139/85-89 mm Hg); and 50,810 with
      hypertension (over 140/90 mm Hg without anti-hypertensive drugs). CKD was defined
      as an estimated glomerular filtration rate of stage 3 or lower or having
      proteinuria greater than 1+ by a dipstick method. The prevalence of CKD among
      patients with optimal blood pressure, prehypertension having normal or high
      normal blood pressure, and hypertension was 13.9, 15.6, 18.1, and 20.7% in men,
      and 10.9, 11.6, 12.9, and 15.0% in women, with a significant difference between
      genders at each strata of blood pressure. In men, but not in women, whose blood
      pressure was high-normal, the CKD risk was significantly greater (odds ratio
      1.11) than those with optimal blood pressure. Obesity (body mass index over 25)
      was significantly associated with an increased risk of CKD in both men and women
      (odds ratio 1.43 and 1.26, respectively), and there was an additive effect of
      obesity and pre-hypertension on CKD risk in men compared with men with optimal
      blood pressure. Thus, the prevalence of CKD increased with the severity of blood
      pressure. Prehypertension with high-normal blood pressure, particularly in
      conjunction with obesity, was found to be an independent risk factor of CKD in
      men.

PMID- 21956190
TI  - Detection of glomerular complement C3 fragments by magnetic resonance imaging in
      murine lupus nephritis.
AB  - One of the challenges of treating patients with glomerulonephritis is to
      accurately assess disease activity. As renal biopsies are routinely stained for
      deposits of C3 activation fragments and glomerular C3 deposits are found in most
      forms of glomerulonephritis, we sought to determine whether a relatively
      noninvasive measure of C3 fragment deposition in the kidney can serve as a good
      biomarker of disease onset and severity. We recently developed a magnetic
      resonance imaging (MRI)-based method of detecting glomerular C3 and used this to
      track the progression of renal disease in the MRL/lpr mouse model of lupus
      nephritis using superparamagnetic iron oxide nanoparticles conjugated to
      complement receptor type 2 as a targeting agent. Quantitative immunofluorescence
      showed that glomerular C3b/iC3b/C3d deposition progressively increased with
      disease activity, a finding replicated by the T2-weighted MRI. The T2 relaxation
      times decreased with disease activity in the cortex and medulla of the MRL/lpr
      but not in MRL/Mpj control mice. Thus, MRI contrast agents targeted to glomerular
      C3 fragments can be used to noninvasively monitor disease activity in
      glomerulonephritis. As therapeutic complement inhibitors are used in patients
      with renal disease, this method, should it become feasible in humans, may
      identify those likely to benefit from complement inhibition.

PMID- 21956191
TI  - Uridine adenosine tetraphosphate activation of the purinergic receptor P2Y
      enhances in vitro vascular calcification.
AB  - Purinergic signaling has a crucial role in different vascular processes. The
      endothelial-derived vasoconstrictor uridine adenosine tetraphosphate (Up(4)A) is
      a potent activator of the purinoceptor P2Y and is released under pathological
      conditions. Here we sought to measure purinergic effects on vascular
      calcification and initially found that Up(4)A plasma concentrations are increased
      in patients with chronic kidney disease. Exploring this further we found that
      exogenous Up(4)A enhanced mineral deposition under calcifying conditions ex vivo
      in rat and mouse aortic rings and in vitro in rat vascular smooth muscle cells.
      The addition of Up(4)A increased the expression of different genes specific for
      osteochondrogenic vascular smooth muscle cells such as Cbfa1, while decreasing
      the expression of SM22alpha, a marker specific for vascular smooth muscle cells.
      The influence of different P2Y antagonists on Up(4)A-mediated process indicated
      that P2Y(2/6) receptors may be involved. Mechanisms downstream of P2Y signaling
      involved phosphorylation of the mitogen-activated kinases MEK and ERK1/2. Thus,
      Up(4)A activation of P2Y influences phenotypic transdifferentiation of vascular
      smooth muscle cells to osteochondrogenic cells, suggesting that purinergic
      signaling may be involved in vascular calcification.

PMID- 21956192
TI  - Mode of action and effects of standardized collaborative disease management on
      mortality and morbidity in patients with systolic heart failure: the
      Interdisciplinary Network for Heart Failure (INH) study.
AB  - BACKGROUND: Trials investigating efficacy of disease management programs (DMP) in
      heart failure reported contradictory results. Features rendering specific
      interventions successful are often ill defined. We evaluated the mode of action
      and effects of a nurse-coordinated DMP (HeartNetCare-HF, HNC). METHODS AND
      RESULTS: Patients hospitalized for systolic heart failure were randomly assigned
      to HNC or usual care (UC). Besides telephone-based monitoring and education, HNC
      addressed individual problems raised by patients, pursued networking of health
      care providers and provided training for caregivers. End points were time to
      death or rehospitalization (combined primary), heart failure symptoms, and
      quality of life (SF-36). Of 1007 consecutive patients, 715 were randomly assigned
      (HNC: n=352; UC: n=363; age, 69+/-12 years; 29% female; 40% New York Heart
      Association class III-IV). Within 180 days, 130 HNC and 137 UC patients reached
      the primary end point (hazard ratio, 1.02; 95% confidence interval, 0.81-1.30;
      P=0.89), since more HNC patients were readmitted. Overall, 32 HNC and 52 UC
      patients died (1 UC patient and 4 HNC patients after dropout); thus, uncensored
      hazard ratio was 0.62 (0.40-0.96; P=0.03). HNC patients improved more regarding
      New York Heart Association class (P=0.05), physical functioning (P=0.03), and
      physical health component (P=0.03). Except for HNC, health care utilization was
      comparable between groups. However, HNC patients requested counseling for
      noncardiac problems even more frequently than for cardiovascular or heart-failure
      related issues. CONCLUSIONS: The primary end point of this study was neutral.
      However, mortality risk and surrogates of well-being improved significantly.
      Quantitative assessment of patient requirements suggested that besides
      (tele)monitoring individualized care considering also noncardiac problems should
      be integrated in efforts to achieve more sustainable improvement in heart failure
      outcomes. CLINICAL TRIAL REGISTRATION: URL: http://www.controlled-trials.com.
      Unique identifier: ISRCTN23325295.

PMID- 21956193
TI  - Extraordinary selectivity of CoMo(3)S(13) chalcogel for C(2)H(6) and CO(2)
      adsorption.

PMID- 21956196
TI  - Direct renin inhibition in a rat model of chronic allograft injury.
AB  - BACKGROUND: Blockade of the renin-angiotensin system (RAS) with angiotensin
      converting enzyme (ACE) inhibitors or angiotensin II (Ang II) receptor blockers
      (ARBs) slow the progression of various chronic kidney diseases and chronic
      allograft dysfunction. RAS inhibition can be achieved also by directly blocking
      renin upstream from ACE. However, direct renin inhibition can have additional
      effects since formation of renoprotective Ang II breakdown products such as
      angiotensin (Ang) (1-7) that are produced by ACE2 are also inhibited. METHODS:
      Using a Fischer-to-Lewis renal transplantation model, the effect of the renin
      inhibitor aliskiren (10 mg/kg/day) was assessed on the development of chronic
      allograft dysfunction compared with vehicle treatment and Ang II receptor
      blockers candesartan. RESULTS: Aliskiren had no effect on renal function
      (proteinuria, creatinine clearance) or on renal morphological changes
      (glomerulosclerosis collagen deposition, myofibroblast accumulation and
      macrophage infiltration) compared with the vehicle- and candesartan-treated
      animals determined 24 weeks after transplantation. On the other hand, atrophy of
      tubular cells was significantly attenuated. Candesartan reduced both proteinuria
      and structural injury of the kidney. In aliskiren-treated animals reduced serum
      Ang II and Ang (1-7) levels were detected, whereas the level of urine
      angiotensinogen was unchanged. CONCLUSIONS: The renin inhibitor aliskiren does
      not slow the progression of chronic allograft dysfunction. We suggest that the
      lack of protection might be due to reduced formation of the protective Ang II
      breakdown products such as Ang (1-7) or due to unchanged intrarenal RAS activity
      demonstrated by urinary angiotensinogen levels.

PMID- 21956195
TI  - Hydrogen-enriched preservation protects the isogeneic intestinal graft and amends
      recipient gastric function during transplantation.
AB  - BACKGROUND: Inhaled hydrogen gas exerts antioxidant and anti-inflammatory effects
      in rat intestinal transplantation. Here, we investigated whether ex vivo donor
      organ treatment with dissolved hydrogen would prevent intestinal graft injury.
      METHODS: Isogeneic intestinal transplantation was performed in Lewis rats with
      vascular flush, luminal preservation, and cold graft storage in nitrogen-bubbled
      (SITxN2) or hydrogen-bubbled (SITxH2) preservation solution. Lactated Ringer's
      solution and 3-hr cold ischemia time were used for mechanistic investigations,
      whereas survival experiments were performed with University of Wisconsin solution
      and 6-hr cold ischemia time. RESULTS: During the early phase of ischemia
      reperfusion injury, hydrogen-enriched solution significantly preserved mucosal
      graft morphology, diminished graft malondialdehyde levels demonstrating
      substantial reduction potential and blunted proinflammatory molecular responses
      (early growth response gene [EGR-1], interleukin [IL]-6, IL-1beta, and inducible
      nitric oxide synthase) within the reperfused intestinal graft muscularis. During
      the late phase of ischemia-reperfusion injury, circulating IL-6 protein and
      lactate dehydrogenase levels were significantly ameliorated in SITxH2 animals,
      which were associated with a favorable functional outcome in in vivo liquid
      gastrointestinal transit and recipient solid gastric emptying of chrome steel
      balls, and marked prevention of the posttransplant associated suppression of in
      vitro muscarinic jejunal contractility. Reflecting improved graft preservation,
      hydrogen preloading of grafts increased recipient survival rates from 41% to 80%.
      Anti-inflammatory and antiapoptotic heme oxygenase-1 was significantly
      upregulated in the hydrogen-treated graft muscularis but not mucosa before
      reperfusion. CONCLUSIONS: Graft preloading with hydrogen demonstrated superior
      morphologic and functional graft protection in rodent intestinal transplantation,
      ultimately facilitating recipient survival. Antioxidant capacity and muscularis
      heme oxygenase-1 upregulation are possible protective mechanisms.

PMID- 21956197
TI  - Nonobese diabetic natural killer cells: a barrier to allogeneic chimerism that
      can be reduced by rapamycin.
AB  - BACKGROUND: Induction of allogeneic hematopoietic chimerism is a promising
      strategy to induce tolerance to donor islets for treating type 1 diabetes.
      Successful induction of chimerism requires overcoming host alloimmunity. In
      diabetes-prone nonobese diabetic (NOD) mice, this is challenging due to their
      general tolerance resistance. Although the adaptive alloimmunity of NOD mice is a
      known barrier to allogeneic chimerism, whether NOD natural killer (NK) cells are
      an additional barrier has not been examined. Because NOD NK cells exhibit
      functional defects, they may not inhibit chimerism generation. METHODS: Antibody
      depletion of NK cells in vivo, or transplantation of F1 hybrid donor cells to
      eliminate the "missing-self" trigger of NK cells, was preformed to test the NK
      mediated rejection of donor bone marrow cells. We also studied the capacity of
      rapamycin to block the NK cell response against allogeneic cells in vivo.
      RESULTS: Depleting NK cells or rendering them unresponsive to the donor greatly
      improved the level of chimerism obtained in NOD mice. Rapamycin significantly
      reduced the resistance to allogeneic chimerism mounted by NOD NK cells; however,
      it was much less effective than NK cell depletion by antibodies. CONCLUSIONS:
      Contrary to the view that NOD NK cells are defective, we found these cells to be
      a substantial barrier to allogeneic chimerism in the presence or absence of
      adaptive immunity. Moreover, rapamycin will need to be combined with other
      approaches to fully overcome the NK cell barrier.

PMID- 21956198
TI  - Improving live donor kidney transplant guidelines: more evidence required.

PMID- 21956200
TI  - A quantitative survey of Western Muslim attitudes to solid organ donation.
AB  - BACKGROUND: It is imperative for healthcare providers to examine Western Muslim
      attitudes on organ donation, because they are reluctant donors. We explored such
      opinion with the aid of a quantitative survey. METHODS: Voluntary completion of
      an anonymous survey was promoted (online and paper sampling). For a population
      target of approximately 1.6 billion, we targeted a completed sample size of 664
      to achieve 5% error margins and 99% confidence intervals (assuming 50% response
      distribution). Logistic regression analysis was performed to assess independent
      predictors for organ donation approval. RESULTS: In total, 891 global Muslims
      took the survey with 728 full completions (81.7% completion rate). Paper survey
      (14% of total) response rate was 62% (124 completed/200 distributed). Western
      Muslims comprised 76% of participants (n=675) and formed the basis of the
      analysis. A total of 68.5% of Western Muslims agreed with organ donation, but
      just 39.3% believed it was compatible with Islam (only 12.7% were registered
      donors). A total of 1.9% would refuse an organ transplant if required, with 72.4%
      happy to receive and 25.7% undecided. The main constraints cited by Western
      Muslims were interpretation of religious scripture (76.5%) and advice from local
      mosque (70.2%). Predictors for organ donation approval among all global Muslims
      included younger age, lesser degree of self-rated religiosity, awareness of organ
      shortages, higher education, and knowing someone with kidney disease/dialysis
      (all P<0.05). CONCLUSION: Concern exists among Western Muslims regarding organ
      donation. Our speculative work should form the basis of larger and more
      representative assessment of global Muslims to facilitate targeted initiatives to
      raise awareness.

PMID- 21956199
TI  - Plasma neutrophil gelatinase-associated lipocalin in kidney transplantation and
      early renal function prediction.
AB  - BACKGROUND: This prospective observational study aimed to assess the relevance of
      serial postoperative plasma neutrophil gelatinase-associated lipocalin (NGAL)
      measurements on prediction of early renal transplant function. METHODS: Plasma
      NGAL (pNGAL) was measured (Triage NGAL Test; Biosite Inc., Inverness Medical) in
      41 patients scheduled for kidney transplantation from deceased or living donors,
      immediately before and after surgery, and at 12 hr, day 1, day 3, and day 7. A
      delayed graft function (DGF) was defined as the need for dialysis during the
      first week. The results were expressed as median (Q1, Q3). RESULTS: Of the 41
      consecutive patients enrolled, all had a high preoperative pNGAL level: 453 ng/mL
      (382, 595). Fifteen (36.6%) presented a DGF. In patients with DGF, pNGAL was
      significantly higher at 12 hr (571 [467, 634] vs. 242 [158, 299] ng/mL, P<0.0001)
      and at day 1 (466 [356, 627] vs. 165 [91, 248] ng/mL, P<0.0001). A pNGAL higher
      than 400 ng/mL 12 hr after transplantation predicted DGF with a sensitivity of
      93.3%, a specificity of 88.5%, and an odds ratio of 63.2 (P=0.0004). This
      predictive performance was higher than for plasma creatinine. CONCLUSIONS: pNGAL
      level early and accurately predicted DGF after renal transplantation. pNGAL
      measurements allowed monitoring of the renal function in this striking situation
      of ischemia-reperfusion aggression. Early identification of patients at risk of
      DGF, before graft lesions are consolidated, opens the field of a precise
      monitoring of renal injury and the impact of future protective therapeutics.

PMID- 21956201
TI  - Everolimus prevents endomyocardial remodeling after heart transplantation.
AB  - BACKGROUND: Endomyocardial remodeling is characterized by progressive fibrosis
      and scars and may develop after heart transplantation. The role of everolimus in
      preventing this process has not been evaluated as yet. METHODS: We prospectively
      studied 132 patients at baseline pretransplant and at 4 weeks, 1 year, and 3
      years after heart transplantation. Fibrosis, scars (Zeiss Vision, in Sirius), and
      acute cellular rejection (hematoxylin-eosin) were studied in biopsy. Transplant
      vasculopathy was assessed by coronary angiography (focal stenoses, peripheral
      obliterations, negative vascular remodeling defined by peripheral obliterations,
      and diffusely narrowed proximal and mid vessel segments). RESULTS: Patients on
      everolimus versus patients on mycophenolate mofetil presented with significantly
      less fibrosis at 4 weeks (3.8%+/-0.3% vs. 5.5%+/-0.3%, P=0.007), 1 year (4.1%+/
      0.3% vs. 4.8%+/-0.3%, P=0.015), and 3 years (4.2%+/-0.3% vs. 5.5%+/-0.7%,
      P=0.049) posttransplant and showed less scarring at 3 years posttransplant
      (19.9+/-1.9% vs. 31.9+/-4.6% vs. baseline biopsy 26.0+/-2.8%; P=0.017).
      Angiographic peripheral obliterations correlated with higher amounts of
      endomyocardial fibrosis. The negative correlation of everolimus and the positive
      correlation of peripheral obliterations with fibrosis were confirmed by
      regression analysis. Angiographic stenoses or acute cellular rejection had no
      effect on the development of fibrosis. Negative vascular remodeling in 1-year
      follow-up tended to be less frequent in everolimus-treated patients (24% vs. 76%;
      P=0.053). CONCLUSIONS: Everolimus prevents endomyocardial remodeling after heart
      transplantation and might have beneficial effects on vascular remodeling of
      epicardial coronary arteries too. Angiographic peripheral obliterations correlate
      with increased amounts of endomyocardial fibrosis, suggesting a relevant effect
      on microvascular perfusion.

PMID- 21956202
TI  - Effect of smoking on kidney transplant outcomes: analysis of the United States
      Renal Data System.
AB  - BACKGROUND: We investigated the effect of smoking on postkidney transplant
      outcomes in the United States Renal Data System. METHODS: In a retrospective
      cohort of 41,705 adult Medicare primary renal transplant recipients in the United
      States Renal Data System database transplanted from January 1, 2000, to June 30,
      2006, and followed through October 31, 2006, we assessed Medicare claims for
      smoking. The association between renal allograft loss and death and smoking as a
      time-dependent variable was assessed with Cox nonproportional hazards regression.
      RESULTS: Of 41,705 Medicare primary adult renal transplant patients, there were
      9.9% patients who had evidence of prior smoking and 4.6% patients with new claims
      for smoking after transplant. Incident smoking (new onset smokers) occurred at a
      mean of 1.29+/-0.88 years after transplant. In the adjusted analysis, factors
      associated with new smoking included male gender, history of drug or alcohol use,
      history of chronic obstructive pulmonary disease, and later year of transplant.
      Compared with never smokers, incident smoking after transplant was associated
      with increased risk of death-censored allograft loss (adjusted hazard ratio [AHR]
      1.46 [95% confidence interval {CI}: 1.19-1.79]; P<0.001) and death (AHR 2.32 [95%
      CI: 1.98-2.72]; P<0.001). In a sensitivity analysis excluding patients with
      history of chronic obstructive pulmonary disease, similar results were obtained
      with increased risk of death-censored allograft loss (AHR 1.43 [95% CI: 1.16
      1.76]; P=0.001) and death (AHR 2.26 [95% CI: 1.91-2.66]; P<0.001). DISCUSSION:
      Incident smoking was detrimental to graft and patient survival. Transplant
      programs should screen those at risk during transplant follow-up and have smoking
      cessation programs.

PMID- 21956203
TI  - Impact of accidental discovery of renal cell carcinoma at time of renal
      transplantation on patient or graft survival.
AB  - BACKGROUND: Renal tumors are common in the pretransplant end-stage renal disease
      population. Their impact on transplant outcome has not been well addressed.
      METHODS: This study is a retrospective follow-up observational study conducted in
      258 renal transplant recipients. All patients had an ipsilateral native
      nephrectomy at the time of transplantation. We reviewed the histopathology of all
      native nephrectomies to gauge the prevalence of renal cell carcinoma (RCC) and to
      investigate the impact of accidental discovery of RCC on graft and patient
      outcome. RESULTS: RCC was found in 12 patients (4.7%): clear type in 9 patients,
      and chromophobe and combined clear and papillary type in 1 and 2 patients,
      respectively. There was no significant difference in human leukocyte antigen
      mismatch, primary immunosuppression, occurrence of rejection, graft function, and
      patient and graft survival between patients with or without RCC. RCC presented in
      the other native kidney in three patients (25%) posttransplantation and one of
      them developed metastasis 4 years after renal transplantation in the RCC group in
      comparison with eight patients in the control group (3.3%; P<0.001). The median
      follow-up period was 56 months for the RCC group and 65 months for the control
      group. CONCLUSIONS: We found that renal transplant outcome and patient survival
      were not adversely affected by the presence of accidently discovered RCC at the
      time of transplantation. These patients seem to be at significantly higher risk
      of the occurrence of RCC in the remaining native kidney. Further studies are
      warranted to confirm our results.

PMID- 21956204
TI  - Attenuation by targeting the B- and T-cell attenuator.

PMID- 21956205
TI  - Genome-wide identification of TCF7L2/TCF4 target miRNAs reveals a role for miR-21
      in Wnt-driven epithelial cancer.
AB  - Transcription factor 7 like 2 (TCF7L2, also known as TCF4) is a Wnt signaling
      pathway transcription factor involved in regulation of numerous Wnt targeted
      genes. Recently, thousands of high-confidence TCF4 binding sites were reported in
      LS174T colon carcinoma cells, however, potential TCF4 target miRNAs remain
      largely unknown. Here, we utilized a bioinformatics approach to discover 26 miRNA
      transcription start sites (TSSs) within close proximity to TCF4 chromatin
      occupancy sites, and validated these sites as bona fide TCF4 targets in LS174T
      colon carcinoma cells, MCF-7 breast cancer cells and U87 glioma cells by ChIP
      PCR. We then selected miR-21 to demonstrate for the first time direct TCF4
      transcriptional activation of a miRNA via binding to the promoter region. Tissue
      array analysis supported this finding, revealing a positive correlation between
      activation of the beta-catenin pathway and in situ expression of miR-21. Finally,
      based upon the well known but poorly understood preventive effect of aspirin on
      colorectal cancer incidence and mortality, we report downregulation of miR-21
      upon administration of aspirin. In sum, our findings identify direct
      transcriptional regulation of miR-21 by TCF4 and suggest a role for miR-21 in
      cancer cell proliferation and invasion upon activation of beta-catenin/TCF4
      signaling.

PMID- 21956206
TI  - Engineering analysis of the effects of bulging sinuses in a newly designed
      pediatric pulmonary heart valve on hemodynamic function.
AB  - The purpose of this study was to examine the hemodynamic characteristics of
      expanded polytetrafluoroethylene (ePTFE) pulmonary valves with bulging sinuses
      quantitatively in a pediatric pulmonary mechanical circulatory system designed by
      us, in order to propose the optimal design for clinical applications. In this
      study, we developed a pediatric pulmonary mock circulation system, which
      consisted of a pneumatic right ventricular model, a pulmonary heart valve
      chamber, and a pulmonary elastic compliance tubing with resistive units. The
      hemodynamic characteristics of four different types of ePTFE valves and a
      monoleaflet mechanical heart valve were examined. Relationships between the
      leaflet movements and fluid characteristics were evaluated based on engineering
      analyses using echocardiography and a high-speed video camera under the pediatric
      circulatory conditions of the mock system. We successfully performed hemodynamic
      simulations in our pediatric pulmonary circulatory system that could be useful
      for quantitatively evaluating the pediatric heart valves. In the simulation
      study, the ePTFE valve with bulging sinuses exhibited a large eddy in the
      vicinity of the leaflets, whereas the straight tubing exhibited turbulent flow.
      The Reynolds number obtained in the valve with bulging sinuses was calculated to
      be 1667, which was smaller than that in the straight tubing (R (e) = 2454).The
      hemodynamic characteristics of ePTFE pediatric pulmonary heart valves were
      examined in our mock circulatory system. The presence of the bulging sinuses in
      the pulmonary heart valve decreased the hydrodynamic energy loss and increased
      the systolic opening area. Based on an in vitro experiment, we were able to
      propose an optimal selection of pulmonary valve design parameters that could
      yield a more sophisticated pediatric ePTFE valve shape.

PMID- 21956207
TI  - Holographic investigations of azobenzene-containing low-molecular-weight
      compounds in pure materials and binary blends with polystyrene.
AB  - This paper reports on the synthesis and the thermal and optical properties of
      photochromic low-molecular-weight compounds, especially with respect to the
      formation of holographic volume gratings in the pure materials and in binary
      blends with polystyrene. Its aim is to provide a basic understanding of the
      holographic response with regard to the molecular structure, and thus to show a
      way to obtain suitable rewritable materials with high sensitivity for holographic
      data storage. The photoactive low-molecular-weight compounds consist of a central
      core with three or four azobenzene-based arms attached through esterification.
      Four different cores were investigated that influence the glass transition
      temperature and the glass-forming properties. Additional structural variations
      were introduced by the polar terminal substituent at the azobenzene chromophore
      to fine-tune the optical properties and the holographic response. Films of the
      neat compounds were investigated in holographic experiments, especially with
      regard to the material sensitivity. In binary blends of the low-molecular-weight
      compounds with polystyrene, the influence of a polymer matrix on the behavior in
      holographic experiments was studied. The most promising material combination was
      also investigated at elevated temperatures, at which the holographic recording
      sensitivity is even higher.

PMID- 21956208
TI  - Narrated truths: the image of psychiatry in the media.
AB  - In recent years, we have witnessed an increase in media attention on the subject
      of mental illness, which mass media frequently portray as a new phenomenon
      affecting large sections of the population. Reports about people suffering from
      mental disorders and on psychiatric or psychotherapeutic clinics, however, are
      often characterised by their emphasis on stereotypes and one-sided invariably
      negative attributes both in the choice of wording and the images used. This paper
      is an attempt to elucidate this apparent contradiction from both a narrative and
      a socio-historical perspective. In view of the development of modern moving image
      formats and storytelling techniques, it seeks to identify possible ways of
      harnessing the media to present a more considered and differentiated picture of
      psychiatric disorders and mental illnesses. Professionally moderated discussion
      forums based on social media techniques are to serve just as well as stories that
      take account of the narrative universals such as reward, success and human
      relations.

PMID- 21956209
TI  - Treatment of pediatric status epilepticus.
AB  - OPINION STATEMENT: Status epilepticus is characterized by a prolonged, self
      sustaining seizure or repeated seizures without return to baseline. The clinical
      manifestations of status epilepticus in children and adults range from overt
      generalized convulsions to more subtle behavioral manifestations, including
      unresponsiveness in the setting of the intensive care unit. Status epilepticus is
      the most common neurologic emergency of childhood. A large proportion of these
      episodes are the result of a prolonged febrile seizure or an acute symptomatic
      etiology. Fortunately, status epilepticus occurs without consequence for many
      children, but for others, it is correlated with long-term neurologic dysfunction
      or death. Treatment of status epilepticus should commence promptly upon its
      recognition, using predefined treatment protocols. The goal of treatment is the
      rapid termination of the seizure, to minimize the acute and chronic effects of
      this emergency and to allow for the prompt assessment and management of the
      underlying precipitant. Currently, the drug class of first choice in the in
      hospital and out-of-hospital treatment of status epilepticus is the
      benzodiazepines, which may need to be quickly followed by a next-line agent, as
      the efficacy of the benzodiazepines is negatively correlated with seizure
      duration. Traditionally, these next-line agents have included phenobarbital and
      phenytoin, but emerging evidence supports the use of intravenous formulations of
      other antiepileptic drugs. If the first two agents fail, high-dose intravenous
      midazolam or anesthetic therapy should be rapidly initiated. This paper reviews
      the current treatment options and strategies for pediatric patients with status
      epilepticus.

PMID- 21956210
TI  - Dual HER2-targeted approaches in HER2-positive breast cancer.
AB  - Approximately 15-20% of all breast cancers are human epidermal growth factor
      receptor 2 (HER2) positive, with clinical studies having validated the HER2
      receptor tyrosine kinase pathway as an important therapeutic target. Presently,
      two HER2-targeted therapies are approved by the Food and Drug Administration for
      treatment of HER2-positive breast cancer: the HER2-targeted humanized monoclonal
      antibody trastuzumab and the small-molecule tyrosine kinase inhibitor lapatinib.
      Despite use of these HER2-targeted agents, many patients still experience disease
      progression. For this reason, numerous new agents and therapeutic strategies are
      under investigation. Based on preclinical data suggesting synergistic effects
      from dual therapy targeting HER2, clinical trials that test the effects of
      combining anti-HER2 agents have been conducted and are ongoing. Here, we review
      recently presented data from several clinical trials, which indicate that the
      strategy of combining HER2 blockade therapies can offer greater clinical
      efficacy, with adverse effects of varying degrees. Specifically, we review new
      data reported at the 2010 San Antonio Breast Cancer Symposium (SABCS 2010),
      including the phase II NeoSphere and phase III NeoALTTO clinical trials, and data
      from three clinical trials reported at the 2011 American Society of Clinical
      Oncology (ASCO 2011) meeting. Together these trials elucidate the potential role
      of combining trastuzumab with lapatinib or pertuzumab. We also discuss additional
      ongoing studies that will help further define the role of dual HER2 blockade
      therapies and its impact on clinical practice.

PMID- 21956211
TI  - Combination therapy inhibits development and progression of mammary tumours in
      immunocompetent mice.
AB  - We have determined the effect of combining the chemotherapy agent doxorubicin and
      the anti-resorptive drug zoledronic acid on the early stages of spontaneous
      mammary tumour development using the immunocompetent PyMT mouse model that
      closely mimics human breast cancer development. 6-week-old PyMT mice were treated
      weekly for 6 weeks with PBS, 2 mg/kg doxorubicin, 100 MUg/kg zoledronic acid or
      doxorubicin followed 24 h later by zoledronic acid (n = 15/group). Untreated, 6
      week-old animals were used for comparison of tumour development. Tumour volume,
      apoptosis and angiogenesis were analysed on H&E, caspase 3, CD31 and CD34 stained
      histological sections. Proliferation was measured by BrdU incorporation and Ki67
      staining and tumour macrophage infiltration assessed by F4/80
      immunohistochemistry. Animals treated with doxorubicin followed by zoledronic
      acid did not develop palpable mammary tumours, whereas in all other treatment
      groups tumours progressed to late stage adenocarcinomas. Tumours from the
      combination treatment group were of comparable size to those in 6-week-old
      untreated animals, remaining pre-malignant with well-differentiated acinar
      arrangements and with tumour volume only reaching on average 26% of that in the
      PBS control group. Tumour cell apoptosis and proliferation was significantly
      reduced compared to control, single agent or untreated 6-week-old mice.
      Significantly fewer circulating tumour cells were present in animals following
      sequential treatment compared to all other groups. Combination treatment with
      doxorubicin followed by zoledronic acid inhibits development and progression of
      spontaneously occurring mammary tumours.

PMID- 21956212
TI  - Quality of life among Egyptian women with breast cancer after sparing mastectomy
      and immediate autologous breast reconstruction: a comparative study.
AB  - Breast reconstruction is considered as an integrated part of the modern breast
      surgery. The aim of this study is to evaluate whether immediate autologous breast
      reconstruction influences QOL and patient satisfaction outcomes among Egyptian
      women with breast cancer in comparison to the traditional mastectomy. This is a
      prospective study in which 200 Egyptian women with non metastatic breast cancer
      were included; group I (100 patients) underwent sparing mastectomy with immediate
      autologous breast reconstruction and group II (100 patients) underwent
      traditional mastectomy. The patient satisfaction with breast reconstruction was
      evaluated by special questionnaire and the reasons given by traditional
      mastectomy patients for not having breast reconstruction were recorded. Both
      breast impact of treatment scale (BITS) and body satisfaction scale (BSS) were
      evaluated in both groups. Patient satisfaction with breast reconstruction had a
      high mean score of 14.44 out of total degrees of 20 and most of them voted yes
      for having the same reconstruction again if they were offered it and would
      recommend reconstruction to other patients. No difference was found between the
      two groups as regard the BITS score. However, the BSS score showed a higher score
      among the reconstruction group. Egyptian ladies with breast cancer show better
      QOL and body image satisfaction outcomes following immediate breast
      reconstruction.

PMID- 21956213
TI  - Adjuvant therapy, not mammographic screening, accounts for most of the observed
      breast cancer specific mortality reductions in Australian women since the
      national screening program began in 1991.
AB  - There has been a 28% reduction in age-standardised breast cancer mortality in
      Australia since 1991 when the free national mammographic program (BreastScreen)
      began. Therefore, a comparative study between BreastScreen participation and
      breast cancer age specific mortality trends in Australia was undertaken for two
      time periods between 1991 and 2007, where women aged 50-59 and 60-69 years, who
      were invited to screen, were compared to women aged 40-49 and 70-79 years who
      were not invited, but who did have access to the program. There were mortality
      reductions in all four age groups between 1991-1992 and 2007, resulting in 5,849
      (95% CI 4,979 to 6,718) fewer women dying of breast cancer than would have
      otherwise been the case. Women aged 40-49 years, who had the lowest BreastScreen
      participation (approximately 20%), had the largest mortality reduction: 44% (95%
      CI 34.8-51.2). Women aged 60-69 years, who had the highest BreastScreen
      participation (approximately 60%), had the smallest mortality reduction: 19% (95%
      CI 10.5-26.9). As BreastScreen participation by invited women aged 50-69 years
      only reached a maximum of about 55-60% in 1998-1999, a decline in mortality in
      Australian women cannot be attributed to BreastScreen prior to this time. Thus,
      almost 60% of the Australian decline in breast cancer mortality since 1991 cannot
      be attributed to BreastScreen. Therefore, mammographic screening cannot account
      for most of the reductions in breast cancer mortality that have occurred in
      Australian women since 1991 and may have contributed to over-diagnosis. Most, if
      not all, of the reductions can be attributed to the adjuvant hormonal and
      chemotherapy, which Australian women have increasingly received since 1986.

PMID- 21956215
TI  - Analysis of clinical interventional strategy for women with urinary incontinence
      complicated with diabetes mellitus.
AB  - INTRODUCTION AND HYPOTHESIS: This study aims to investigate clinical therapeutic
      measures for women with urinary incontinence (UI) complicated with diabetes
      mellitus (DM). METHODS: We performed a retrospective cohort study, including 462
      female patients with UI complicated with DM (group A) and 901 patients with UI
      without DM (group B). Both A and B groups were divided into three subgroups
      according to their UI types (pure stress UI, mixed UI dominated by urge UI, and
      by overactive bladder syndrome) and received corresponding treatments. The
      subjective and objective effective rates were analyzed statistically. RESULTS:
      The overall subjective effective rates were 62.99% and 85.23% and the overall
      objective effective rates were 67.53% and 87.24% for groups A and groups B,
      respectively; the subjective and objective effective rates were 73.68% and 89.47%
      for group A1 (patients with pure stress UI in group A). There was no statistical
      difference in group A1 between subjective and objective effective rates.
      CONCLUSION: Unsatisfactory clinical therapeutic efficacy was observed in women
      with UI complicated with DM; surgical operation should be deliberated cautiously
      for women with SUI complicated with DM.

PMID- 21956216
TI  - Luminescent metal complexes of d6, d8 and d10 transition metal centres.
AB  - This highlight focuses on various luminescent complexes with different transition
      metal centres of d(6), d(8) and d(10) electronic configurations. Through the
      systematic study on the variation of ligands, structural and bonding modes of
      different metal centres, the structure-property relationships of the various
      classes of luminescent transition metal complexes can be obtained. With the
      knowledge and fundamental understanding of their photophysical behaviours, their
      electronic absorption and luminescence properties can be fine-tuned. Introduction
      of supramolecular assembly with hierarchical complexity involving non-covalent
      interactions could lead to research dimensions of unlimited possibilities and
      opportunities. The approach of "function by design" could be employed to explore
      and exploit the potential applications of such luminescent transition metal
      complexes for future development of luminescent materials.

PMID- 21956217
TI  - Purine receptors and Ca(2+) signalling in the human blood-brain barrier
      endothelial cell line hCMEC/D3.
AB  - The expression and physiology of purine receptors of the human blood-brain
      barrier endothelial cells were characterised by application of molecular
      biological, gene-silencing and Ca(2+)-imaging techniques to hCMEC/D3 cells.
      Reverse transcription polymerase chain reaction showed the expression of the G
      protein-coupled receptors P2Y(2)-, P2Y(6)-, P2Y(11)- as well as the ionotropic
      P2X(4)-, P2X(5)- and P2X(7)-receptors. Fura-2 ratiometry revealed that adenosine
      triphosphate (ATP) or uridine triphosphate (UTP) mediated a change in the
      intracellular Ca(2+) concentration ([Ca(2+)](i)) from 150 to 300 nM in single
      cells. The change in [Ca(2+)](i) corresponded to a fourfold to fivefold increase
      in the fluorescence intensity of Fluo-4, which was used for high-throughput
      experiments. Pharmacological dissection using different agonists [UTPgammaS,
      ATPgammaS, uridine diphosphate (UDP), adenosine diphosphate (ADP), BzATP,
      alphabeta-meATP] and antagonist (MRS2578 or NF340) as well as inhibitors of
      intracellular mediators (U73122 and 2-APB) showed a PLC-IP(3) cascade-mediated
      Ca(2+) release, indicating that the nucleotide-induced Ca(2+) signal was mainly
      related to P2Y(2, 6 and 11) receptors. The gene silencing of the P2Y(2) receptor
      reduced the ATP- or UTP-induced Ca(2+) signal and suppressed the Ca(2+) signal
      mediated by P2Y(6) and P2Y(11) more specific agonists like UDP (P2Y(6)), BzATP
      (P2Y(11)) and ATPgammaS (P2Y(11)). This report identifies the P2Y(2) receptor
      subtype as the main purine receptor involved in Ca(2+) signalling of the hCMEC/D3
      cells.

PMID- 21956218
TI  - Luminescence quenching in self-assembled adducts of [Ru(dpp)3]2+ complexes and
      CdTe nanocrystals.
AB  - We have investigated chloroform solutions containing tris(4,7-diphenyl-1,10
      phenanthroline) ruthenium(II) and CdTe nanocrystal quantum dots (5.6 nm
      diameter). The electronic levels of these two components are such that the Ru
      complex can act as an energy donor towards the quantum dot, which can thus behave
      as an energy acceptor. Steady-state and time-resolved spectroscopic experiments
      indicate that the Ru complexes and the CdTe nanocrystals self-assemble to give
      stable 1 : 1 adducts, in which the luminescence of the former units is strongly
      quenched. Such a quenching can be ascribed to either energy transfer to the CdTe
      quantum dot, or to electron transfer from the CdTe valence band to the excited Ru
      complex. However, no supporting evidence for the occurrence of photoinduced
      energy transfer in the adduct could be found. The CdTe luminescence is also
      slightly quenched in the presence of the ruthenium complex. The strong
      association of the metal complexes with the nanocrystals suggests that self
      assembly strategies may be effectively employed to achieve surface
      functionalization of semiconductor quantum dots with molecular units.

PMID- 21956219
TI  - A murine model of neurofibromatosis type 1 tibial pseudarthrosis featuring
      proliferative fibrous tissue and osteoclast-like cells.
AB  - Neurofibromatosis type 1 (NF1) is a common genetic condition caused by mutations
      in the NF1 gene. Patients often suffer from tissue-specific lesions associated
      with local double-inactivation of NF1. In this study, we generated a novel
      fracture model to investigate the mechanism underlying congenital pseudarthrosis
      of the tibia (CPT) associated with NF1. We used a Cre-expressing adenovirus
      (AdCre) to inactivate Nf1 in vitro in cultured osteoprogenitors and osteoblasts,
      and in vivo in the fracture callus of Nf1(flox/flox) and Nf1(flox/-) mice. The
      effects of the presence of Nf1(null) cells were extensively examined. Cultured
      Nf1(null)-committed osteoprogenitors from neonatal calvaria failed to
      differentiate and express mature osteoblastic markers, even with recombinant bone
      morphogenetic protein-2 (rhBMP-2) treatment. Similarly, Nf1(null)-inducible
      osteoprogenitors obtained from Nf1 MyoDnull mouse muscle were also unresponsive
      to rhBMP-2. In both closed and open fracture models in Nf1(flox/flox) and
      Nf1(flox/-) mice, local AdCre injection significantly impaired bone healing, with
      fracture union being <50% that of wild type controls. No significant difference
      was seen between Nf1(flox/flox) and Nf1(flox/-) mice. Histological analyses
      showed invasion of the Nf1(null) fractures by fibrous and highly proliferative
      tissue. Mean amounts of fibrous tissue were increased upward of 10-fold in
      Nf1(null) fractures and bromodeoxyuridine (BrdU) staining in closed fractures
      showed increased numbers of proliferating cells. In Nf1(null) fractures, tartrate
      resistant acid phosphatase-positive (TRAP+) cells were frequently observed within
      the fibrous tissue, not lining a bone surface. In summary, we report that local
      Nf1 deletion in a fracture callus is sufficient to impair bony union and
      recapitulate histological features of clinical CPT. Cell culture findings support
      the concept that Nf1 double inactivation impairs early osteoblastic
      differentiation. This model provides valuable insight into the pathobiology of
      the disease, and will be helpful for trialing therapeutic compounds.

PMID- 21956220
TI  - A 10-year experience with treatment of high and standard risk Hodgkin disease:
      six cycles of tailored BEACOPP, with interim scintigraphy, are effective and
      female fertility is preserved.
AB  - Therapy of Hodgkin lymphoma (HL) is designed to prolong survival and minimize
      toxicity. A total of 124 patients with newly diagnosed HL and adverse prognostic
      factors were prospectively studied between July, 1999 and August, 2005. Patients
      with early unfavorable and advanced disease were eligible for the study. Patients
      were assigned to therapy based on international prognostic score (IPS). Those
      with IPS >= 3 received three cycles of escalated BEACOPP (EB). All others
      received two cycles of standard BEACOPP (SB). Subsequent therapy was
      prospectively assigned according to early interim GA(67) or positron emission
      tomography (PET)/computerized tomography (CT). Four cycles of EB or SB were
      administered following a positive or negative scan, respectively. Complete
      remission rate, 10-year progression free (PFS), and overall survival (OS) were
      97, 87, and 88%, respectively, at a median follow-up of 89 months (5-144). PFS
      and OS were similar in both groups. Fertility status was assessed in 38 females
      aged <40 years; 94% of females younger than 40 years preserved their cyclic
      ovarian function. Nineteen conceived during follow-up for 30 pregnancies,
      delivering 24 babies. Deliveries were reported up to 7 years from diagnosis.
      Predictive value of negative interim Ga(67) or PET/CT was 87 and 93%,
      respectively. Six cycles of tailored BEACOPP, for patients with adverse
      prognostic factors, provide encouraging long-term PFS and OS, and fertility is
      preserved in most females.

PMID- 21956221
TI  - The estrogen elixir: hormone replacement therapy in American medicine and
      culture.

PMID- 21956222
TI  - A retrospective look at prescription drug safety: oral contraceptives and
      thromboembolic disease in the 1960s.

PMID- 21956223
TI  - Point of view: can the medical community welcome part-time female physicians?

PMID- 21956224
TI  - Improving women's health is a shared priority.

PMID- 21956225
TI  - How can physicians address patient concerns about radiation exposure?

PMID- 21956226
TI  - How Margaret Sanger and John Rock changed the world.

PMID- 21956227
TI  - Repairing the communication disconnect.

PMID- 21956228
TI  - Lend me your ears and your huddled masses: conversations with New Jersey
      patients.

PMID- 21956229
TI  - Bulk heterojunction photovoltaic cells with low donor concentration.

PMID- 21956230
TI  - The impact of the number of cores on tissue microarray studies investigating
      prostate cancer biomarkers.
AB  - Most tissue microarray studies have used a single 0.6-mm tissue core per donor
      tissue. It has been suggested that multiple cores per donor can increase the
      representativity of tissue microarray studies. To estimate the potential benefit
      of multiple cores, we analyzed Ki67 and p53 in triplet cores taken from three
      different areas of 3,261 prostate cancer tissue blocks. Both p53 and Ki67
      labeling index were linked to advanced tumor stage (p<0.0001 each), Gleason score
      (p<0.0001), and early PSA recurrence (p<0.0001) independently of whether the 3
      tissue spots were analyzed separately or combined for a consensus result. The
      rate of positive findings increased with the amount of analyzed tissue. The
      average Ki67 labeling index was higher in tumors with 3 interpretable spots
      (5.3+/-5.6) as compared to two (4.1+/-4.7) or one interpretable spot (4.1+/-4.2,
      p<0.0001). For p53, tumors with three interpretable spots were positive in 3.8%
      of cases, and tumors with 1 or 2 interpretable spots in 1.9% only (p=0.003).
      These data demonstrate that using multiple cores in a tissue microarray does not
      necessarily increase the ability to identify associations of biomarkers with
      tumor phenotype and prognosis but has always the disadvantage of additional work
      and tissue requirements. Multiple cores may even lead to statistical problems if
      unequal amounts of tissue are analyzed per tumor.

PMID- 21956231
TI  - Microarray analysis of 1,25(OH)2D3 regulated gene expression in human primary
      osteoblasts.
AB  - Though extensive studies have been conducted, questions regarding the molecular
      effectors and pathways underlying the regulatory role of 1,25(OH)(2)D(3) in human
      osteoblasts other than cell differentiation and matrix protein production remain
      unanswered. This study aims to identify genes and pathways that are modulated by
      1,25(OH)(2)D(3) treatment in human osteoblasts. Primary osteoblast cultures
      obtained from human bone tissue samples were treated with 1,25(OH)(2)D(3) (10(-7)
      M) for 24 h and their transcritptomes were profiled by microarray analysis using
      the Affymetrix GeneChip. Statistical analysis was conducted to identify genes
      whose expression is significantly modulated following 1,25(OH)(2)D(3) treatment.
      One hundred and fifty-eight genes were found to be differentially expressed. Of
      these, 136 were upregulated, indicating clear transcriptional activation by
      1,25(OH)(2)D(3). Biostatistical evaluation of microarray data by Ingenuity
      Pathways Analysis (IPA) revealed a relevant modulation of genes involved in
      vitamin D metabolism (CYP24), immune functions (CD14), neurotransmitter
      transporters (SLC1A1, SLC22A3), and coagulation [thrombomodulin (THBD), tissue
      plasminogen activator (PLAT), endothelial protein C receptor (PROCR), thrombin
      receptor (F2R)]. We identified a restricted number of highly regulated genes and
      confirmed their differential expression by real-time quantitative PCR (RT qPCR).
      The present genome-wide microarray analysis on 1,25(OH)(2)D(3) -treated human
      osteoblasts reveals an interplay of critical regulatory and metabolic pathways
      and supports the hypothesis that 1,25(OH)(2)D(3) can modulate the coagulation
      process through osteoblasts, activates osteoclastogenesis through inflammation
      signaling, modulates the effects of monoamines by affecting their reuptake.

PMID- 21956233
TI  - Is DAS28-CRP with three and four variables interchangeable in individual patients
      selected for biological treatment in daily clinical practice?
AB  - DAS28 is a widely used composite score for the assessment of disease activity in
      patients with rheumatoid arthritis (RA) and is often used as a treatment decision
      tool in the daily clinic. Different versions of DAS28 are available. DAS28-CRP(3)
      is calculated based on three variables: swollen and tender joint counts and CRP.
      DAS28-CRP(4) also includes patient global assessment. Thresholds for low and high
      disease activity are the same for the two scores. Based on the Bland-Altman
      method, the interchangeability between DAS28-CRP with three and four variables
      was examined in 319 RA patients selected for initiating biological treatment.
      Data were extracted from the Danish registry for biological treatment in
      rheumatology (DANBIO). Multiple regression analysis was used to assess the
      predictability of the DAS28 scores by several measures of disease activity. The
      overall mean DAS28-CRP was 4.7 +/- 1.2. The mean difference between the two
      scores (the bias) was -0.29 +/- 0.33 (CI -0.33, -0.25) (p < 0.0001). Upper and
      lower limits of agreement were -0.95 (CI -1.01, -0.89) and 0.37 (CI 0.31, 0.43),
      respectively. Tender joint count was the most important predictor of both DAS28
      CRP(4) (beta = 0.52, p < 0.0001) and DAS28-CRP(3) (beta = 0.62, p < 0.0001). The
      second most important predictor of DAS28-CRP(4) was patient global assessment
      (beta = 0.32, p < 0.0001) which did not add to the prediction of DAS28-CRP(3). In
      conclusion, overall DAS28-CRP(3) was only slightly underestimated compared to
      DAS28-CRP(4). In the individual patient, however, the two scores may differ
      considerably. The scores should not be used interchangeably in the daily clinic
      without caution.

PMID- 21956234
TI  - Heptavalent pneumococcal conjugate vaccine elicits similar antibody response as
      standard 23-valent polysaccharide vaccine in adult patients with RA treated with
      immunomodulating drugs.
AB  - The objectives of the study were to compare antibody response in immunosuppressed
      patients with rheumatoid arthritis (RA) after vaccination with heptavalent
      pneumococcal conjugate vaccine (PCV7) to that of RA patients and healthy controls
      vaccinated with 23-valent polysaccharide vaccine (PPV23) and to study the impact
      of disease and/or treatment characteristics and type of vaccine on antibody
      response following pneumococcal vaccination in patients with RA. In total, 253 RA
      patients treated with methotrexate (MTX), anti-TNF blockers as monotherapy or
      anti-TNF + MTX were vaccinated with a single dose (0.5 ml) of PCV7. In addition,
      149 RA patients receiving corresponding treatments and 47 healthy controls were
      vaccinated with a single dose (0.5 ml) of PPV23. Serotype-specific IgG to 23F and
      6B were measured at vaccination and 4-6 weeks after vaccination using ELISA.
      Antibody response ratio (ARR), i.e. ratio between post-/prevaccination antibody
      levels, was compared between corresponding treatment groups. Differences in ARR
      were analysed using analysis of variance. Positive antibody response (posAR) was
      defined as equal to or greater than twofold increase in prevaccination antibody
      levels. Possible predictors of posAR were analysed using logistic regression
      model. Corresponding RA treatment groups showed similar ARR and posAR for both
      serotypes regardless of vaccine type. Higher age at vaccination and concomitant
      MTX were identified as predictors of impaired posAR for both serotypes tested,
      whereas type of vaccine did not influence posAR significantly. PCV7 elicits
      similar antibody response as PPV23 in patients with RA receiving
      immunosuppressive treatment. In RA patients, higher age and MTX treatment but not
      type of vaccine predicted impaired posAR.

PMID- 21956235
TI  - Monthly or weekly bisphosphonate? Evaluation of satisfaction in patients with
      postmenopausal osteoporosis using OPSAT-Q questionnaire during the BOOSTER study
      in Croatia.
AB  - A prospective, open-labelled, multicentre 6-month study was designed to assess
      three categories that have high impact on Health-Related Quality of Life (HR
      QoL). These categories were: satisfaction, preference and drug tolerability in
      postmenopausal patients with osteoporosis in Croatia, at first treated with
      weekly oral bisphosphonates, followed by monthly oral ibandronate. Three hundred
      eighty-five postmenopausal women who were treated with one of the weekly
      bisphosphonates for at least 6 months were included into the study and after they
      had signed written informed consent, the therapy was changed to monthly
      ibandronate. Satisfaction with the treatment was assessed with the Osteoporosis
      Patient Satisfaction Questionnaire (OPSAT-Q). Patients completed OPSAT-Q at the
      baseline visit before the change of therapy (visit 1) and 6 months after the
      change of therapy (visit 2). Following 6 months ibandronate therapy, the values
      in all four domains of the OPSAT-Q (convenience, confidence with daily
      activities, overall satisfaction, side effects) as well as in the Composite
      Satisfaction Score were higher in visit 2 (p < 0.001). Values in subjects
      enrolled into the patient assistance programme did not differ significantly from
      the values in subjects that were not (p = 0.399) except for the domain
      convenience (p = 0.026). This study demonstrates significantly higher
      satisfaction in patients who switched from the weekly bisphosphonate therapy
      regimen to monthly ibandronate in all observed aspects of treatment. Patients
      expressed preference for monthly bisphosphonate (ibandronate) in comparison with
      weekly bisphosphonates and found it to be a more convenient method of treatment.
      At the time of study, however, it was not known that the anti-fracture effect of
      ibandronate was smaller for hip fractures than with other bisphosphonates.

PMID- 21956236
TI  - Whole-genome sequencing informs treatment: personalized medicine takes another
      step forward.

PMID- 21956237
TI  - Synthetic applications of the nickel-catalyzed cyclization of alkynes combined
      with addition reactions in a domino process.
AB  - Carbonickelations of alkynes and functionalization of the resulting vinylnickel
      moiety have been performed efficiently in a nickel-catalyzed domino cyclization
      condensation process. This reaction, which does not require the preparation of
      any other organometallic reagent, proceeds only by exo-dig cyclization. This
      convenient and mild method constitutes a one-pot synthesis of substituted
      dihydrobenzofurans, chromans, isochromans, indoles, or indanes. Theses valuable
      products are generally obtained in good yields and high stereoselectivity. They
      are shown to be useful synthons for rapid access to functionalized polycyclic
      skeletons.

PMID- 21956238
TI  - Viability and membrane potential analysis of Bacillus megaterium cells by
      impedance flow cytometry.
AB  - Single cell analysis is an important tool to gain deeper insights into microbial
      physiology for the characterization and optimization of bioprocesses. In this
      study a novel single cell analysis technique was applied for estimating viability
      and membrane potential (MP) of Bacillus megaterium cells cultured in minimal
      medium. Its measurement principle is based on the analysis of the electrical cell
      properties and is called impedance flow cytometry (IFC). Comparatively, state-of
      the-art fluorescence-based flow cytometry (FCM) was used to verify the results
      obtained by IFC. Viability and MP analyses were performed with cells at different
      well-defined growth stages, focusing mainly on exponential and stationary phase
      cells, as well as on dead cells. This was done by PI and DiOC(2)(3) staining
      assays in FCM and by impedance measurements at 0.5 and 10 MHz in IFC. In
      addition, transition growth stages of long-term cultures and agar plate colonies
      were characterized with both methods. FCM and IFC analyses of all experiments
      gave comparable results, quantitatively and qualitatively, indicating that IFC is
      an equivalent technique to FCM for the study of physiological cell states of
      bacteria.

PMID- 21956240
TI  - Suppression of cocaine self-administration in monkeys: effects of delayed
      punishment.
AB  - RATIONALE: Delaying presentation of a drug can decrease its effectiveness as a
      reinforcer, but the effect of delaying punishment of drug self-administration is
      unknown. OBJECTIVE: This study examined whether a histamine injection could
      punish cocaine self-administration in a drug-drug choice, whether delaying
      histamine would decrease its effectiveness, and whether the effects of delay
      could be described within a delay discounting framework. METHODS: Monkeys were
      implanted with double-lumen catheters to allow separate injection of cocaine and
      histamine. In discrete trials, subjects first chose between cocaine (50 or 100
      MUg/kg/inj) alone and an injection of the same dose of cocaine followed
      immediately by an injection of histamine (0.37-50 MUg/kg). Next, they chose
      between cocaine followed immediately by histamine and cocaine followed by an
      equal but delayed dose of histamine. RESULTS: When choosing between cocaine alone
      and cocaine followed immediately by histamine, preference increased with
      histamine dose from indifference to >80% choice of cocaine alone. When choosing
      between cocaine followed by immediate histamine and cocaine followed by delayed
      histamine, monkeys showed strong position preferences. When delayed histamine was
      associated with the nonpreferred position, preference for that option increased
      with delay from <=30% to >85%. The corresponding decrease in choice of the
      preferred position was well described by a hyperboloid discounting function.
      CONCLUSIONS: Histamine can function as a punisher in the choice between
      injections of cocaine and delay can decrease its effectiveness as a punisher. The
      effects of delaying punishment of drug self-administration can be conceptualized
      within the delay discounting framework.

PMID- 21956241
TI  - Does minocycline, an antibiotic with inhibitory effects on microglial activation,
      sharpen a sense of trust in social interaction?
AB  - RATIONALE: Minocycline has long been applied to various infectious diseases as a
      tetracycline antibiotic and recently has found new application in the treatment
      of brain diseases such as stroke and multiple sclerosis. In addition, minocycline
      has also been suggested as an effective drug for psychiatric diseases. These
      suggestions imply that minocycline may modulate our mental activities, while the
      underlying mechanism remains to be clarified. OBJECTIVE: To investigate how
      minocycline influences human mental activity, we experimentally examined how
      minocycline works on human social decision making in a double-blind randomized
      trial. METHODS: Forty-nine healthy volunteers were administered minocycline or
      placebo over four days, after which they played (1) a trust game, in which they
      decided how much to trust an anonymous partner, and (2) a dictator game, in which
      they decided how to divide resources between themselves and an anonymous partner.
      RESULTS: The minocycline group did not display increased trusting behavior or
      more altruistic resource allocation. In fact, the minocycline group displayed a
      slight reduction in trusting behavior. However, the minocycline group did show a
      strong positive correlation between the degree of risk taking in the trust game
      and in a separate evaluation of others' trustworthiness, whereas the placebo
      group showed no such correlation. CONCLUSIONS: These results suggest that
      minocycline led to more rational decision-making strategies, possibly by
      increasing emotion regulation. Since minocycline is a well-known inhibitor of
      microglial activation, our findings may open a new optional pathway for treating
      mental states in which a component of rational decision making is impaired.

PMID- 21956239
TI  - Neurohypophyseal hormones manipulation modulate social and anxiety-related
      behavior in zebrafish.
AB  - RATIONALE: Oxytocin (OT) and arginine-vasopressin (AVP) regulate social behavior
      in mammals. Zebrafish (Danio rerio) allows higher throughput and ease in studying
      human brain disorders. OBJECTIVES: This study investigated in zebrafish the
      effect of non-mammalian homologs isotocin (IT) and vasotocin (AVT) in comparison
      with OT/AVP on social behavior and fear response to predator. The mechanism was
      studied using the most human selective OT and AVP receptor antagonists. METHODS:
      Zebrafish were injected i.m. with increasing doses (0.001-40 ng/kg) of the
      neuropeptides. DesGly-NH(2)-d(CH(2))(5)-[D-Tyr(2),Thr(4)]OVT) for OT receptor, SR
      49059 for V1a subtype receptor, and SSR-149415 for V1b subtype receptor were
      injected i.m. 10 min before each agonist. RESULTS: All the peptides increased
      social preference and reduced fear to predator response in a dose-dependent
      manner interpolated by symmetrical parabolas. AVT/AVP were more potent to elicit
      anxiolytic than social effect while IT and OT were equally potent. All the
      antagonists dose-dependently inhibited both the effects induced by the
      neuropeptides. The ratio between the ED50 obtained for blocking the OT-induced
      effects on social preference and fear response to predator was very high only for
      desglyDTTyrOVT (160). SR49059 showed the highest ratio in blocking AVP-induced
      effects (807). The less selective antagonist appeared to be SSR149415.
      CONCLUSIONS: For the first time, IT/AVT and OT/AVP were found to modulate in
      zebrafish, social behavior, unrelated to sex, and fear to predator response
      through at least two different receptors. Zebrafish is confirmed as a valid,
      reliable model to study deficit in social behavior characteristic of some
      psychiatric disorders.

PMID- 21956242
TI  - Highly active iridium(I) complexes for the selective hydrogenation of carbon
      carbon multiple bonds.
AB  - New iridium(I) complexes, bearing a bulky NHC/phosphine ligand combination, have
      been established as extremely efficient hydrogenation catalysts that can be used
      at low catalyst loadings, and are compatible with functional groups which are
      often sensitive to more routinely employed hydrogenation methods.

PMID- 21956245
TI  - Effect of water on glass transition in starch/sucrose matrices investigated
      through positron annihilation lifetime spectroscopy: a new approach.
AB  - Glass transition is studied through positron annihilation lifetime spectroscopy
      (PALS) in maize starch matrices containing 10 (batch STS10) and 20 (STS20) w/w%
      sucrose, as a function of temperature (T) and water content (c(w)). To circumvent
      important losses of water upon heating while recording the PALS spectra, a new
      method is developed: instead of a series of measurements of tau(3), the triplet
      positronium lifetime, at different T, the latter is kept constant and the series
      relates to c(w), which is left to decrease at a constant rate. Similarly to the
      changes in tau(3) with T, the tau(3)vs. c(w) plots obtained show a smooth linear
      increase until a break, denoting the occurrence of glass transition, followed by
      a sharper increase. The gradients appear to be independent of T. The variation of
      the glass transition temperature, T(g), with c(w) shows a broad sigmoid with a
      large linear central part; as expected from the plasticising effect of sucrose,
      the plot for STS20 lies some 10 K below that for STS10. Results from differential
      scanning calorimetry for STS20 yield T(g) values some 15 K higher than from PALS.
      On the basis of the general shape of the tau(3)vs. T variations, a general
      equation is set for tau(3)(T, c(w)), leading one to expect a similar shape for
      tau(3)vs. c(w), as experimentally observed.

PMID- 21956244
TI  - Regulation of the polymeric immunoglobulin receptor and IgA transport: new
      advances in environmental factors that stimulate pIgR expression and its role in
      mucosal immunity.
AB  - Secretory IgA (SIgA) antibodies represent the first line of antigen-specific
      immune defense protecting the mucosal surfaces against environmental pathogens
      and antigens, and maintaining homeostasis with the commensal microbiota. The
      polymeric immunoglobulin receptor (pIgR) has the dual role of transporting
      locally produced dimeric IgA across mucosal epithelia, and serving as the
      precursor of secretory component, a glycoprotein that enhances the immune
      functions of SIgA. The complex regulation of pIgR expression and transcytosis by
      host and microbial factors is finely tuned to optimize the role of SIgA in
      mucosal immunity. Disruption of this regulatory network in disease states similar
      to inflammatory bowel disease can result in profound consequences for mucosal
      homeostasis and systemic sequelae. Future research into the function and
      regulation of pIgR and SIgA may offer new insights into the prevention and
      treatment of infectious and inflammatory diseases that originate at mucosal
      surfaces.

PMID- 21956246
TI  - Gay men talking about health: are sexuality and health interlinked?
AB  - Defining and describing health has traditionally been the role of medical
      experts. Although a rich literature has recently established the importance of
      lay accounts of health, one important gap relates to gay men's accounts of
      health. Data from 11 focus groups involving 45 gay men were thematically analyzed
      to investigate gay men's views of health. Two contrasting positions on a possible
      relationship between sexuality and health-there is no link or there is a definite
      link-were identified. In addition, five key ways gay men talked about health were
      identified: health is the absence of disease, is functional ability, is fitness
      and exercise, is psychological, and is multifaceted. Although there are
      similarities in the ways gay and other men talk about health, important
      differences exist, which suggest that issues of sexuality need to be considered
      by health policy and service planners so that responsive health services can be
      provided.

PMID- 21956248
TI  - Vibrational modes and structural characteristics of (Ba(0.3)Sr(0.7))[(Zn(x)Mg(1
      x))(1/3)Nb(2/3)]O3 solid solutions.
AB  - (Ba(0.3)Sr(0.7))[(Zn(x)Mg(1-x))(1/3)Nb(2/3)]O(3) (BSZMN) (x = 0.0, 0.2, 0.4, 0.6,
      0.8, 1.0) solid solution ceramics were synthesized by the conventional solid
      state sintering technique. Vibration spectra (Raman spectroscopy and Fourier
      transform far-infrared reflection spectroscopy, short for FTIR) and X-ray
      diffraction (XRD) were employed to evaluate the correlation between crystal
      structures and vibration modes of these solid solutions as a function of Mg(2+)
      ions replaced by Zn(2+) ions. It is verified that these ceramics present a phase
      transition, i.e., the crystal structure changes from hexagonal phase (P 3m1,
      where x<= 0.4) to the pseudocubic phase (I4/mcm, where x>= 0.8) with increasing
      Zn(2+) content. The phase transition is a gradual process, the sample where x =
      0.6 is of the transition phase, i.e., at x = 0.6, phase transition begins to
      appear from hexagonal phase to pseudocubic phase but is not complete. The phase
      transition is also verified by the FTIR spectra. Tilting of oxygen octahedra is
      the main reason for the phase transition. The phonon modes of the vibration
      spectra were assigned, the position and width were determined, and the
      correlation of phonon vibrations with the microstructure for the different atoms
      substituted in B'-site was found.

PMID- 21956247
TI  - Screening for male osteoporosis at an academic medical center: retrospective
      analysis of DXA usage patterns over 5 years.
AB  - Recent findings suggest that men have higher mortality rates than women after a
      hip fracture. Although the risk of osteoporotic fractures in men is increasing,
      male osteoporosis still remains underdiagnosed and undertreated. In general, male
      osteoporosis is given low priority by policy makers in public health initiatives.
      The purpose of this study is to examine the patterns of use and gender
      distribution of DXA (dual-energy X-ray absorptiometry) scan usage at a university
      medical center in the United States. The total number of DXA scans increased
      during the study period while the percentage of men studied actually declined.
      The results of this study may lead to heightened awareness among providers who
      are caring for male patients at risk for osteoporosis.

PMID- 21956250
TI  - Neonatal acute kidney injury in a tertiary center in a developing country.
AB  - BACKGROUND: Acute kidney injury (AKI) is a common contributor to morbidity and
      mortality in newborns, with prevalences varying by population and hospital. A
      study of AKI in newborns in tertiary care centers in Thailand, a developing
      country with limited resources, has not been conducted yet. METHODS: The aim of
      this study was to determine the prevalence of AKI in newborns in a tertiary care
      hospital in southern Thailand and to investigate the etiology, mortality and risk
      factors of mortality. The records of patients aged <30 days with high serum
      creatinine, admitted from 1984 to 2007, were retrospectively reviewed. RESULTS:
      Eighty-eight boys and 51 girls were enrolled; 61.4% were premature and 56.5% had
      a birth weight <2500 g. The prevalence of newborn AKI increased from 0.9 to 6.3%
      during the 24-year study period. Thirty-nine and 65% had renal failure within 2
      and 7 days post-birth, respectively. Sepsis was the most common cause of AKI
      (30.9%) followed by hypovolemia (18.7%), kidney, ureter and bladder (KUB)
      anomalies (12.2%), congestive heart failure (12.2%) and birth asphyxia (11.5%).
      Indomethacin caused AKI in 24.4% with gestational age <32 weeks. Sepsis-induced
      AKI had the highest mortality rate (65.1%) with an overall mortality rate of
      38.8% and nearly 14 times the risk of death compared to hypovolemia-induced AKI.
      CONCLUSIONS: The prevalence of newborn AKI in our Thai tertiary center over 24
      years was 6.3% of admitted newborns. Sepsis was the most common cause of AKI and
      sepsis-induced AKI is the most common cause of death. Disease etiology was the
      only risk factor for mortality.

PMID- 21956251
TI  - On-pump beating-heart coronary artery bypass provides efficacious short- and long
      term outcomes in hemodialysis patients.
AB  - BACKGROUND: On-pump beating-heart coronary artery bypass grafting surgery (CABG)
      is beneficial due to the elimination of cardioplegic arrest. However, there are
      few reports regarding its efficacy in chronic hemodialysis patients. This study
      investigated the potential benefits of on-pump beating-heart CABG in chronic
      hemodialysis patients. METHODS: From January 2002 to January 2010, 186 patients
      with chronic hemodialysis underwent CABG in our institution. In total, 82
      patients underwent conventional CABG with cardioplegic arrest, 56 underwent off
      pump CABG and 48 underwent on-pump beating-heart CABG. The early results and long
      term outcomes were compared among these three groups. RESULTS: On-pump beating
      heart CABG significantly reduced the duration of cardiopulmonary bypass (CPB)
      compared with conventional CABG. The post-operative pericardial drainage amount
      (P < 0.01), length of hospital stay (P < 0.001) and length of post-operative
      intensive care unit stay (P < 0.001) were significantly lower in the on-pump
      beating-heart and off-pump CABG groups than in the conventional CABG group. No
      significant difference was found regarding 30-day mortality and morbidity rates
      including stroke, pneumonia, arrhythmia, intestinal complication and low cardiac
      output syndrome. There were no statistical differences in the freedom from
      cardiac events (P = 0.323), but on-pump beating-heart CABG provided better long
      term survival than conventional CABG (P = 0.009). CONCLUSIONS: On-pump beating
      heart CABG is a safe procedure that provides optimal operative exposure in
      chronic hemodialysis patients. The use of CPB and the elimination of cardioplegic
      arrest may be beneficial for the short- and long-term survival of chronic
      hemodialysis patients.

PMID- 21956252
TI  - Apomorphine-induced necrotic ulcers.

PMID- 21956253
TI  - Invasive implantation and intimate placental associations in a placentotrophic
      African lizard, Trachylepis ivensi (scincidae).
AB  - In the viviparous lizard Trachylepis ivensi (Scincidae) of central Africa,
      reproducing females ovulate tiny ~1 mm eggs and supply the nutrients for
      development by placental means. Histological study shows that this species has
      evolved an extraordinary placental pattern long thought to be confined to
      mammals, in which fetal tissues invade the uterine lining to contact maternal
      blood vessels. The vestigial shell membrane disappears very early in development,
      allowing the egg to absorb uterine secretions. The yolk is enveloped precocially
      by the trilaminar yolk sac and no isolated yolk mass or yolk cleft develops.
      Early placentas are formed from the chorion and choriovitelline membranes during
      the neurula through pharyngula stages. During implantation, cells of the
      chorionic ectoderm penetrate between uterine epithelial cells. The penetrating
      tissue undergoes hypertrophy and hyperplasia, giving rise to sheets of epithelial
      tissue that invade beneath the uterine epithelium, stripping it away. As a
      result, fetal epithelium entirely replaces the uterine epithelium, and lies in
      direct contact with maternal capillaries and connective tissue. Placentation is
      endotheliochorial and fundamentally different from that of all other viviparous
      reptiles known. Further, the pattern of fetal membrane development (with
      successive loss and re-establishment of an extensive choriovitelline membrane) is
      unique among vertebrates. T. ivensi represents a new extreme in placental
      specializations of reptiles, and is the most striking case of convergence on the
      developmental features of viviparous mammals known.

PMID- 21956254
TI  - Polycaprolactone microspheres as carriers for dry powder inhalers: effect of
      surface coating on aerosolization of salbutamol sulfate.
AB  - This study reports the factors controlling aerosolization of salbutamol sulfate
      (SS) from mixtures with polycaprolactone (PCL) microspheres fabricated using an
      emulsion technique with polyvinyl alcohol (PVA) as stabilizer. The fine particle
      fraction (FPF) of SS from PCL measured by a twin-stage impinger was unexpectedly
      found to be zero, although scanning electron microscopy showed that the drug
      coated the entire microsphere. Precoating the microspheres with magnesium
      stearate (MgSt) excipient solutions (1%-2%) significantly increased (p < 0.05, n
      = 5) the FPF of SS (11.4%-15.4%), whereas precoating with leucine had a similar
      effect (FPF = 11.3 +/- 1.1%), but was independent of the solution concentration.
      The force of adhesion (by atomic force microscopy) between the PCL microspheres
      and SS was reduced from 301.4 +/- 21.7 nN to 110.9 +/- 30.5 nN and 121.8 +/- 24.6
      nN, (p < 0.05, n = 5) for 1% and 2% MgSt solutions, respectively, and to 148.1 +/
      21.0 nN when coated with leucine. The presence of PVA on the PCL microspheres
      (detected by X-ray photoelectron spectroscopy) affected the detachment of SS due
      to strong adhesion between the two, presumably due to capillary forces acting
      between them. Precoating the microspheres with excipients increased the FPF
      significantly by reducing the drug-carrier adhesion.

PMID- 21956256
TI  - Conduction at domain walls in insulating Pb(Zr0.2 Ti0.8)O3 thin films.
AB  - Domain wall conduction in insulating Pb(Zr(0.2) Ti(0.8))O(3) thin films is
      demonstrated. The observed electrical conduction currents can be clearly
      differentiated from displacement currents associated with ferroelectric
      polarization switching. The domain wall conduction, nonlinear and highly
      asymmetric due to the specific local probe measurement geometry, shows thermal
      activation at high temperatures, and high stability over time.

PMID- 21956255
TI  - Pharmacokinetics of micafungin in HIV positive patients with confirmed esophageal
      candidiasis.
AB  - Esophageal candidiasis (EC) is a common and serious complication in patients
      infected with the human immunodeficiency virus (HIV). Micafungin has been shown
      to have dose-related efficacy and to be well tolerated in patients with HIV and
      EC. This analysis of data from a randomized, double-blind study examined
      pharmacokinetic parameters of micafungin (dosed at 50, 100, and 150 mg/day) and
      its metabolites in a subset of patients with HIV and EC. Micafungin exhibited
      linear, predictable pharmacokinetics, similar to the previous observations in
      healthy control subjects. Micafungin peak plasma concentration and exposure were
      increased with dose, while half-life and clearance remained consistent with
      increasing dose. Plasma concentrations of the metabolites M-1, M-2, and M-5
      remained low throughout the study (24 h exposure <=14% relative to micafungin at
      end of therapy for each). No differences in micafungin pharmacokinetic parameters
      were observed according to the sex or race of the patients. The high systemic
      exposures associated with micafungin 100 and 150 mg/day relative to micafungin 50
      mg/day were found to directly correlate with endoscopic clearance. These data
      provide evidence that the pharmacokinetics of micafungin underlie the dose
      related efficacy in patients with HIV and EC.

PMID- 21956257
TI  - Pentadecyl phenol- and cardanol-functionalized fluorescent, room-temperature
      liquid-crystalline perylene bisimides: effect of pendant chain unsaturation on
      self-assembly.
AB  - A new perylene bisimide (PBI) building block based on pentadecyl phenol (PDP) or
      cardanol was developed, which upon esterification with 3,4,5-tridodecyloxy
      gallate resulted in highly emissive, room-temperature liquid-crystalline (LC)
      molecules. The self assembly in solution was studied in detail by NMR
      spectroscopy, UV/Vis absorption, and fluorescence spectroscopy. In solution both
      PDP- and cardanol-based PBI exhibited similar behavior. They were molecularly
      dissolved in chloroform (CHCl(3)) but formed rotationally displaced H-type
      aggregates that emitted at 640 nm in methylcyclohexane (MCH). Surface morphology
      in dropcast films were characterized using microscopic techniques such as SEM,
      TEM, and atomic force microscopy (AFM). The liquid-crystalline properties were
      studied using differential scanning calorimetry (DSC), polarized light microscopy
      (PLM), and variable-temperature X-ray (small-angle X-ray scattering (SAXS) and
      wide-angle X-ray diffraction (WXRD)) studies. Variable-temperature X-ray studies
      in the LC phase indicated strong pi-pi stacking interaction present in the PDP
      based PBI derivative, whereas the stacking was absent in the LC phase of the
      cardanol-based PBI. The latter formed self-organized structures of extremely
      short length due to the presence of cis double bonds in the C15 alkyl side chain,
      whereas the saturated alkyl side chain in PDP could pack efficiently, thereby
      resulting in nanofibers that were several micrometers in length.

PMID- 21956258
TI  - Using the "write" resources: nursing student evaluation of an interdisciplinary
      collaboration using a professional writing assignment.
AB  - Nursing students need the necessary resources to successfully complete a
      professional paper writing assignment. The purpose of this article is to describe
      resource support and evaluation strategies used in a professional paper writing
      assignment in a baccalaureate nursing program. The impetus for the study is to
      address the need for nursing faculty to move students toward writing proficiency
      while improving their information management skills. Students need resources to
      successfully complete professional papers due to the need for mining relevant
      professional sources, assistance with editing, and refinement of paper gained
      through peer feedback. Methods include evaluation of the interdisciplinary
      resource collaboration with campus librarians (information literacy), campus
      writing center tutorial oversight, and peer reviewer support and feedback.
      Student evaluation of the teaching strategy found the resources helpful for
      completion of the writing assignment and the collaborative learning with campus
      colleagues and writing experts beneficial.

PMID- 21956259
TI  - Nursing student experiences with face-to-face learning.
AB  - Face-to-face learning has been the mainstay of nursing student learning. Despite
      moves to online learning, face-to-face learning persists. This study focuses on
      how nursing students experience face-to-face learning and why it not only
      survives, but thrives. This study was anchored in a hermeneutic phenomenological
      approach, with Gadamerian concepts and van Manen's lifeworlds as frameworks to
      understand students' experiences of face-to-face learning. Patterns and themes
      were extracted from audiore-corded face-to-face interviews. Participants
      confirmed that face-to-face learning continues to be valued as a strong
      methodology in nursing education. Their experiences focused on humanism, the
      importance of "presence," physical proximity, classroom as "the real thing,"
      immediacy of feedback, and learning and knowing by human connections and
      interaction. The study findings were a rich source for understanding how nursing
      students process learning experiences. Increased understanding of the meaning and
      essence of face-to-face learning is essential as we decide how nursing content
      will be taught.

PMID- 21956260
TI  - Validating a tool that explores factors influencing the adoption of principles of
      evidence-based practice.
AB  - The adoption of principles of evidence-based practice in nursing education
      assists nursing graduates in improving their practice. Measuring factors that
      influence this adoption requires the use of a valid tool; however, few tools
      addressing these factors are available. This study measured the psychometric
      properties of a composite tool developed to assess factors influencing the
      adoption of the principles of evidence-based practice in nursing education. A
      descriptive, cross-sectional research design was used. A convenience, purposive
      sample of 85 nurse educators participated in this study. The Evidence-Based
      Nursing Education Questionnaire items were derived following a four-step
      approach: extensive literature review, thematic analysis of literature, expert
      opinion in the questionnaire items, and psychometric testing of the
      questionnaire. The psychometric properties indicated a valid and reliable tool.
      The resulting five factors include knowledge in educational principles and
      faculty practice. The questionnaire proved to be reliable and valid.

PMID- 21956261
TI  - Eighth advanced study course on optical chemical sensors--ASCOS.

PMID- 21956262
TI  - Biosensors for the detection of waterborne pathogens.
AB  - Waterborne bacterial, viral and parasitic pathogens are a global health concern
      and their rapid and specific detection in contaminated potable water is of utmost
      importance. Biosensors using a variety of biorecognition molecules and
      transduction methodologies have been reported, and have the potential to enable
      highly sensitive detection of the analyte of interest in a short time with high
      specificity. However, there are several obstacles to the detection of waterborne
      pathogens-they tend to be present at very low concentrations in the environment
      and environmental samples contain numerous inhibitors of enzymatic reactions and
      interfering organisms and particulates. Here we present a review of the current
      state of biosensor technology with regard to the improvements needed over
      standard detection methods and the challenges presented by real environmental
      samples. Further, we identify future areas of focus necessary to realize novel
      detection devices capable of supplanting the gold standards of today.

PMID- 21956263
TI  - Absolute quantification of free glutathione and cysteine in aquatic insects using
      isotope dilution and selected reaction monitoring.
AB  - A simple and robust isotope dilution mass spectrometry-based assay was developed
      for the determination of free cysteine and glutathione (GSH) in aquatic insects.
      Several experimental parameters were evaluated and optimized to provide specific
      and sensitive detection of both compounds by in situ derivatization with N
      ethylmaleimide followed by acid alkylation quenching and reverse-phased liquid
      chromatography coupled with selected reaction monitoring. For both targets, the
      assay was evaluated over a concentration range of 0.313 to 320 MUM and was
      demonstrated to have a quantitative dynamic range spanning nearly three orders of
      magnitude, with lower limits of quantification being 0.330 MUM for GSH and 0.370
      MUM for cysteine. Additionally, measurements were observed to be highly
      reproducible over the course of several days. When applied to the analysis of
      four different species of insects, large biological variation between and within
      species was observed. Different feeding regimens were also tested within two
      species of insects but statistical comparisons revealed no significant difference
      in the levels of either compound.

PMID- 21956264
TI  - Multiclass determination of 66 organic micropollutants in environmental water
      samples by fast gas chromatography-mass spectrometry.
AB  - A multiresidue method has been developed for quantification and identification of
      66 multiclass priority organic pollutants in water by fast gas chromatography
      (GC) coupled to mass spectrometry (MS). Capabilities and limitations of single
      quadrupole mass spectrometer as detector in fast GC were studied evaluating the
      chromatographic responses in terms of sensitivity and chromatographic peak
      shapes, as they were influenced by scan time. The number of monitored ions in a
      selected ion monitoring (SIM) group strongly conditioned the scan time and
      subsequently the number of data points per peak. A compromise between peak shape
      and scan time was adopted in order to reach the proper conditions for
      quantitative analysis. An average of 10-15 points per peak was attained for most
      compounds, involving scan times between 0.1 and 0.22 s. The method was validated
      for mineral, surface, and groundwater. A solid-phase extraction pre-concentration
      step using C(18) cartridges was applied. Four isotopically labeled standards were
      added to the samples before extraction and used as surrogates to ensure a
      reliable quantification. Analyses were performed by GC-MS in electron ionization
      mode, monitoring the three most abundant and/or specific ions for each compound
      and using the intensity ratios as a confirmatory parameter. With a
      chromatographic run of less than 10 min, SIM mode provided excellent sensitivity
      and identification capability due to the monitoring of three ions and the
      evaluation of their intensity ratio. Limits of detection below 10 ng/L were
      reached for most of the 66 compounds in the three matrices studied. Accuracy and
      precision of the method were evaluated by means of recovery experiments at two
      fortification levels (10 and 100 ng/L), obtaining recoveries between 70% and 120%
      in most cases and relative standard deviations below 20%. The possibilities of a
      simultaneous SIM scan method have also been explored for non-target qualitative
      analysis. The developed method has been applied to the analysis of surface water
      samples collected from the Mediterranean region of Spain.

PMID- 21956265
TI  - Measuring multiple neurochemicals and related metabolites in blood and brain of
      the rhesus monkey by using dual microdialysis sampling and capillary hydrophilic
      interaction chromatography-mass spectrometry.
AB  - In vivo measurement of multiple functionally related neurochemicals and
      metabolites (NMs) is highly interesting but remains challenging in the field of
      basic neuroscience and clinical research. We present here an analytical method
      for determining five functionally and metabolically related polar substances,
      including acetylcholine (quaternary ammonium), lactate and pyruvate (organic
      acids), as well as glutamine and glutamate (amino acids). These NMs are acquired
      from samples of the brain and the blood of non-human primates in parallel by dual
      microdialysis, and subsequently analyzed by a direct capillary hydrophilic
      interaction chromatography (HILIC)-mass spectrometry (MS) based method. To obtain
      high sensitivity in electrospray ionization (ESI)-MS, lactate and pyruvate were
      detected in negative ionization mode whereas the other NMs were detected in
      positive ionization mode during each HILIC-MS run. The method was validated for
      linearity, the limits of detection and quantification, precision, accuracy,
      stability and matrix effect. The detection limit of acetylcholine, lactate,
      pyruvate, glutamine, and glutamate was 150 pM, 3 MUM, 2 MUM, 5 nM, and 50 nM,
      respectively. This allowed us to quantitatively and simultaneously measure the
      concentrations of all the substances from the acquired dialysates. The
      concentration ratios of both lactate/pyruvate and glutamine/glutamate were found
      to be higher in the brain compared to blood (p < 0.05). The reliable and
      simultaneous quantification of these five NMs from brain and blood samples allows
      us to investigate their relative distribution in the brain and blood, and most
      importantly paves the way for future non-invasive studies of the functional and
      metabolic relation of these substances to each other.

PMID- 21956266
TI  - Adaptive evolution for fast growth on glucose and the effects on the regulation
      of glucose transport system in Clostridium tyrobutyricum.
AB  - Laboratory adaptive evolution of microorganisms offers the possibility of
      relating acquired mutations to increased fitness of the organism under the
      conditions used. By combining a fibrous-bed bioreactor, we successfully developed
      a simple and valuable adaptive evolution strategy in repeated-batch fermentation
      mode with high initial substrate concentration and evolved Clostridium
      tyrobutyricum mutant with significantly improved butyric acid volumetric
      productivity up to 2.25 g/(L h), which is the highest value in batch fermentation
      reported so far. Further experiments were conducted to pay attention to glucose
      transport system in consideration of the high glucose consumption rate resulted
      from evolution. Complete characterization and comparison of the glucose
      phosphoenolpyruvate (PEP)-dependent phosphotransferase system (PTS) were carried
      out in the form of toluene-treated cells and cell-free extracts derived from both
      C. tyrobutyricum wide-type and mutant, while an alternative glucose transport
      route that requires glucokinase was confirmed by the phenomena of resistance to
      the glucose analogue 2-deoxyglucose and ATP-dependent glucose phosphorylation.
      Our results suggest that C. tyrobutyricum mutant is defective in PTS activity and
      compensates for this defect with enhanced glucokinase activity, resulting in the
      efficient uptake and consumption of glucose during the whole metabolism.

PMID- 21956267
TI  - Clinical effectiveness of a special silk textile in the treatment of recurrent
      pediatric inflammatory vulvitis: an open label pilot study.
AB  - AIM: Pediatric inflammatory vulvitis (PIV) is clinically characterized by
      itching, soreness and inflammation and can be due to both an infective process
      and a non-specific irritative process, especially in atopic patients. Sometimes
      these non-specific PIVs, that tend to be recurrent, can be overinfected, with
      exacerbation of the clinical features. The importance of the cleansers,
      emollients, and the kind of textiles that enter in direct contact all day long
      with the inflamed skin, is well known. The study objective is the evaluation of
      the safety and efficacy of the transpiring, slightly elastic knitted silk briefs,
      with anti-bacterial and non-irritating properties, registered as Dermasilk(r), in
      recurrent PIV. METHODS: The study we conducted was a prospective cohort study of
      12 pre-pubertal girls, aged between 2 and 10 years, affected by recurrent PIV,
      that used Dermasilk(r) briefs in association to conventional treatments. RESULTS:
      Dermasilk(r) briefs have proven to be an effective and safe adjuvant product
      available for use in association with conventional drugs for the treatment of
      recurrent PIV. CONCLUSION: Dermasilk(r) briefs play an important role in the
      management of the flares of recurrent PIV, proven by an earlier resolution of
      symptoms, as well as in the maintenance of the remission and in the prevention of
      overinfections.

PMID- 21956269
TI  - Melainomania: a study on 100 subjects.
AB  - AIM: The melainomania is a psychological and skin syndrome and it expresses the
      obsessive need of tanned skin in a complete and constant way. We searched for the
      psycho-patogenetic factors of the syndrome and the psychological and skin ends
      point useful to evaluate the psychic and skin damages. METHODS: Seventy-two women
      and 28 men, aged 38-56 years, who were used to a constant photo exposure have
      been examined. We have considered the psychosocial damages by Rorschach e
      Machover tests and by psychologist-subject interviews, skin damages by Glogau
      signs and by echography. Furthermore, the subjects have been submitted to a
      psychotherapeutic treatment. RESULTS: The tests and the interviews have
      underlined obsessive lines, dependence, bodily misperception, low index of
      reality. The Spearman correlations among clinical signs and echographic findings
      shows high significance. The psychotherapy has reduced the uneasiness in 66 women
      and 24 men. Each event that produces uneasiness requires a rationalization
      process that individualizes in successive phases logical justifications for the
      lived uneasiness and for the perceived consequences. The rational psycho
      mechanics is a new method that has identified the phase of the thought-deviation
      and it has planned the corrective therapy. CONCLUSION: The psychological tests,
      the interviews, the clinical signs and the ultrasound have allowed us to appraise
      the psychic and skin damages, while the method of the rational psycho mechanics
      seems to have brought a satisfactory therapeutic result.

PMID- 21956268
TI  - Efficacy of topical hydrating and emollient lotion containing 10% urea ISDIN(r)
      plus dexpanthenol (Ureadin Rx 10) in the treatment of skin xerosis and pruritus
      in hemodialyzed patients: an open prospective pilot trial.
AB  - AIM: Dry skin and pruritus are common complication of end-stage renal diseases
      (ESRD), affecting up to 80% of dialysis patients. They are chronic, unpleasant
      skin manifestations with a strong negative impact on patients' quality of life,
      often inducing sleeplessness and mood disorders. The pathogenesis of skin xerosis
      (SX) and uraemic pruritus (UP) are multifactorial. Moisturizing emollients are
      commonly used for the treatment of SX and UP. Urea is used in dermatology due to
      its excellent hydrating and moisturizing properties. Urea is useful in all cases
      of dry skin and, depending on the concentration levels, will act as moisturizing
      or keratolitic agent. Ureadin Rx 10 is a topical hydrating and emollient lotion
      formulation. So far no data are available regarding the efficacy of topical
      application of urea in lotion in the treatment of SX and UP in dialysed patients.
      In a prospective open pilot trial we assessed the effect of topical 10% Urea
      ISDIN(r) plus dexpanthenol lotion in the treatment of SX and UP in dialyzed
      patients. METHODS: A total of 15 hemodialyzed patients (3 men; 12 women, mean age
      66 years) with SX and UP were enrolled after their informed consent in the trial.
      Topical 10% Urea ISDIN(r) plus dexpanthenol (Ureadin RX; ISDIN) lotion (URx) was
      applied twice daily over the arm and the legs for 28 consecutive days. Primary
      outcomes were a 5-point SRRC Index score (evaluating scaling roughness, redness
      and cracks) and a 4-point itching score (IS) both measured at baseline and after
      2 and 4 weeks of treatment. RESULTS: At baseline mean (SD) SRRC was 5 (2.3).
      After URx treatment SRRC significantly (P=0.0001) decreased to 1.6 (2.1) and to
      0.9 (1.2) after two and four weeks respectively (a relative reduction of 82% at
      week 4). IS at baseline was 1.0 (1.4). URx reduced IS significantly (P=0.008) to
      0.2 (0.5) at week 2 and to 0.06 at week 4 (a relative reduction of 94% at week
      4). Local tolerability was excellent/good in 14 out of 15 patients. One patient
      reported mild burning sensation after application of the product. CONCLUSION: In
      this pilot trial topical application of 10% Urea ISDIN (r) plus dexpanthenol
      lotion has shown to improve skin dryness and pruritus in haemodialysis patients.

PMID- 21956270
TI  - New trends in dermoscopy.
AB  - The dermatologists, in their educational training, learn to observe, recognize
      and classify lesions in order to obtain those stereotypes that allow them to make
      the diagnosis. For this reason, they have not felt the need to develop means to
      flank examination. For some years, however, this sort of prejudice is
      disappearing and also dermatology has begun to make use of semiotics
      instrumental. Among the most tried and tested equipment in clinical practice,
      worth remembering the dermoscopy and digital dermoscopic analysis. The recent
      availability of digital cameras and phones equipped with the latest generation of
      optical systems capable of capturing images of pigmented lesions in
      epiluminescence, has further expanded the range of tools at our disposal.

PMID- 21956271
TI  - Management of skin cancer after organ transplantation.
AB  - Advances in transplant surgery and more effective immunosuppressive regimen have
      led to increased survival rates among transplant recipients. However, intense
      immunosuppression has led to increased rates of both internal and cutaneous
      malignancies, with skin cancer occurring as the most common cancer after
      transplantation. While many transplant recipients will develop mild and
      manageable cutaneous malignancies, some will develop potentially life-threatening
      disease. Dermatologists are an integral part in the care of organ transplant
      recipients. Therefore, it is important for dermatologists to be familiar with the
      available epidemiological data and management of skin cancers in this patient
      population. In this paper, we review the risk factors, prevention, recognition
      and effective intervention of skin cancers in organ transplant recipients.

PMID- 21956272
TI  - Advances in tropical diseases.
AB  - There are six diseases that WHO considers as the major threat in developing
      countries, leprosy, filariasis, malaria, schistosomiasis, Chagas disease and
      leishmaniasis; and of these only malaria does not present skin lesions. These
      diseases are among the so called tropical diseases found in countries of tropical
      climate, usually infections and infestations considered exotic and rare in
      European and North American countries. It is extremely important for doctors of
      all countries to be able to provide correct pre travel counseling and to make
      early diagnosis and treatment, thus avoiding dissemination of these dieases to
      non endemic areas. The authors review some important tropical diseases seen in
      Brazil, as paracoccidiodomycosis, lobomycosis, myiasis, tungiasis, and cutaneous
      schistosomiasis and discuss new information about them.

PMID- 21956273
TI  - Treatment of vitiligo: advantages and disadvantages, indications for use and
      outcomes.
AB  - Topical coticosteroids perform better than placebo and topical PUVAsol in
      repigmenting vitiliginous skin. Topical corticosteroids compare in efficacy to
      topical calcineurin inhibitors, but produce greater adverse events. Calcineurin
      inhibitors are more effective in twice daily dosing and may be used on facial
      areas and in children. Vitamin D analogues are not as effective as topical
      corticosteroids as monotherapy, but can increase effectiveness of topical
      steroids in combination therapy. There are no randomized trials examining
      pseudocatalase monotherapy. With the advent of NB-UVB, oral PUVA is less used in
      the treatment of generalized vitiligo. Topical PUVA may be effectively used for
      the treatment of localized vitiligo. NB-UVB has less side effects and can be used
      in children. Excimer is also as effective as NB-UVB and may be used in the
      treatment of localized vitiligo. NB-UVB and excimer combination therapies show
      some greater effectiveness in repigmentation in vitiligo. All patient undergoing
      surgical repigmentation therapies, including split-thickness skin grafting,
      autologous epidermal non-cultured grafts, suction blistering and punch grafting
      require careful patient selection. Those that have localized, stable vitiligo
      refractory to other treatments are good surgical candidates. Split thickness skin
      grafting has the best cosmetic results, with the least side effects. However,
      scarring of donor and recipient sites is common to split thickness skin grafting.
      Depigmenting treatments include MBEH, 4-MP, and the Q-switched ruby laser. MBEH
      and 4-MP may have similar efficacy, but MBEH has a greater side effect profile
      than 4-MP. Also, visible depigmentation occurs sooner with MBEH as compared with
      4-MP, despite both of them requiring long treatment periods. Relapse with both
      treatments may occur. The Q-switched ruby laser does seem to have the advantage
      of inducing depigmentation more quickly, but with more discomfort.

PMID- 21956274
TI  - Systemic drugs in patients with skin diseases.
AB  - Systemic drugs play an important role in the modern practice of dermatology. The
      purpose of this article is to review systemic therapies in the following
      categories: antifungals, immunosuppressants, retinoids, and biologic
      immunomodulators. We provide a historical perspective, summarize current clinical
      indications, and discuss novel mechanisms of action for each drug. Suggestions
      for dosing regimens and laboratory monitoring are given. To help clinicians
      safely implement these therapies in their practice, we review major adverse
      reactions and clinically important drug interactions of these systemic
      medications in dermatology.

PMID- 21956275
TI  - Predicting internalizing and externalizing problems at five years by child and
      parental factors in infancy and toddlerhood.
AB  - This study examined child and parental factors in infancy and toddlerhood
      predicting subclinical or clinical levels of internalizing and externalizing
      problems at 5 years of age. Ninety-six children and their families participated.
      They were assessed when the children were 4-10 weeks old (T1), 2 years (T2) and 5
      years old (T3). Child risks (difficult temperament, health problems, early
      emotional and behavioral problems), parental risks (psychopathology, parenting
      stress and perception of the child) and family risks (socio-economic status,
      quality of marital relationship and family violence) were examined. At 5 years,
      internalizing problems were predicted by family violence during the child's
      infancy and parenting stress at age 2. Externalizing problems were predicted by
      psychiatric problems of the mother before pregnancy and child's externalizing
      problems at 2 years of age. When interventions aiming at preventing emotional and
      behavioral problems in children are considered, these issues should be recognized
      early and effective intervention initiated.

PMID- 21956276
TI  - Down-regulation of Smad4 enhances proliferation and invasion of colorectal
      carcinoma HCT116 cells and up-regulates Id2.
AB  - The aim of this study was to determine whether the suppression of Smad4 by short
      hairpin RNA (shRNA) regulates the proliferation and invasion of colorectal
      carcinoma HCT116 cells and Id2 expression. The Smad4-shRNA expression vectors
      were constructed and stably transfected to HCT116 cells. The expression of mRNA
      and protein of Smad4 and Id2 was detected using reverse transcription-polymerase
      chain reaction (RT-PCR) and Western blotting. Cellular proliferation inhibitory
      activity was determined by methyl thiazolyl tetrazolium (MTT) assay. Transwell
      assay was used to detect the effect of the inhibition of Smad4-shRNA on migration
      and invasion. The Smad4-shRNA vector, which inhibited Smad4 expression, was
      constructed and successfully transfected to HCT116 cells. The levels of mRNA and
      protein expression of Smad4 were markedly decreased following transfection of
      shRNA compared with the control groups (P<0.05). The abilities of proliferation,
      migration and invasion were increased following transfection of shRNA (P<0.05).
      The expression of Id2 was increased following transfection of shRNA (P<0.05). For
      the Smad4-down-regulated HCT116 cells, treated with or without BMP7 (25 ng/ml),
      no difference was found. shRNA-mediated silencing of Smad4 was able to enhance
      the abilities of proliferation, migration and invasion in the HCT116 cell line.
      Therefore, Smad4 may act as a tumor-suppressor gene in colorectal carcinoma.

PMID- 21956277
TI  - On-line monitoring and active control of dye uptake in dye-sensitised solar
      cells.
AB  - Real-time monitoring of dye loading (N3 and N719) under continuous flow
      conditions on TiO(2) photoanodes for dye-sensitized solar cells has been applied
      to quantitatively investigate dye uptake kinetics, demonstrating that static
      impregnation provides in all cases higher dye loading and, as a consequence,
      better working devices.

PMID- 21956278
TI  - Cytomorphometric and clinical investigation of the gingiva before and after low
      level laser therapy of gingivitis in children.
AB  - Gingival epithelial cells are the first physical barrier against periodontal
      pathogenic microorganisms. Bacterial products may penetrate the epithelium and
      directly disturb its integrity. We investigated the clinical and
      cytomorphological status of the gingiva in children with gingivitis before and
      after low-level laser therapy. The study enrolled 130 children divided into three
      groups: group 1 comprised 50 children with chronic catarrhal gingivitis who
      received basic treatment, group 2 comprised 50 children with chronic catarrhal
      gingivitis who received low-level laser treatment in addition to basic treatment,
      and group 3 comprised 30 children with healthy gingiva as controls. Oral hygiene
      and the status of the gingiva were assessed using the appropriate indexes before
      and after treatment. Inflammation of the gingiva was monitored by
      cytomorphometric evaluation. Cytomorphometric analysis revealed a statistically
      significant difference (p < 0.001) in the size of the nuclei of the stratified
      squamous epithelial cells of the gingiva before and after treatment in chronic
      catarrhal gingivitis. Evaluation using clinical parameters showed that treatment
      of gingivitis with basic treatment was successful. Cytomorphometric analysis
      showed that after basic treatment the nuclei of the stratified squamous
      epithelial cells of the gingiva were reduced in size, although not to the size
      found in healthy gingiva. However, after adjuvant low-level laser therapy, the
      size of the nuclei of the stratified squamous epithelial cells in the gingiva
      matched the size of the nuclei in the cells in healthy gingiva.

PMID- 21956279
TI  - Effects of low-level laser irradiation on mesenchymal stem cell proliferation: a
      microarray analysis.
AB  - Increased proliferation after low-level laser irradiation (LLLI) has been well
      demonstrated in many cell types including mesenchymal stem cells (MSCs), but the
      exact molecular mechanisms involved remain poorly understood. The aim of this
      study was to investigate the change in mRNA expression in rat MSCs after LLLI and
      to reveal the associated molecular mechanisms. MSCs were exposed to a diode laser
      (635 nm) as the irradiated group. Cells undergoing the same procedure without
      LLLI served as the control group. Proliferation was evaluated using the MTS
      assay. Differences in the gene expression profiles between irradiated and control
      MSCs at 4 days after LLLI were analyzed using a cDNA microarray. Gene ontology
      and pathway analysis were used to find the key regulating genes followed by real
      time PCR to validate seven representative genes from the microarray assays. This
      procedure identified 119 differentially expressed genes. Real-time PCR confirmed
      that the expression levels of v-akt murine thymoma viral oncogene homolog 1
      (Akt1), the cyclin D1 gene (Ccnd1) and the phosphatidylinositol 3-kinase,
      catalytic alpha polypeptide gene (Pik3ca) were upregulated after LLLI, whereas
      those of protein tyrosine phosphatase non-receptor type 6 (Ptpn6) and
      serine/threonine kinase 17b (Stk17b) were downregulated. cDNA microarray analysis
      revealed that after LLLI the expression levels of various genes involved in cell
      proliferation, apoptosis and the cell cycle were affected. Five genes, including
      Akt1, Ptpn6, Stk17b, Ccnd1 and Pik3ca, were confirmed and the PI3K/Akt/mTOR/eIF4E
      pathway was identified as possibly playing an important role in mediating the
      effects of LLLI on the proliferation of MSCs.

PMID- 21956281
TI  - No data, no problem, no action: addressing urban health inequity in the 21st
      century.

PMID- 21956282
TI  - Triple-quantum-filtered sodium imaging of the human brain at 4.7 T.
AB  - The limited signal-to-noise ratio of triple-quantum-filtered MRI of sodium is a
      major hurdle for its application clinically. Although it has been shown that
      short 90 degrees  radiofrequency pulses in combination with sufficiently long
      repetition time for full T(1) recovery (labelled "standard" parameters) produce
      the maximum signal through the triple-quantum-filter, and in this work,
      simulation and images of agar phantoms and human brain demonstrate that the use
      of longer radiofrequency pulses and reduced repetition time (optimized parameters
      to accommodate more averages for a constant specific absorption rate, reducing
      noise variance for a given scan length) results in signal-to-noise ratio
      improvement (22 +/- 5% in brain tissue of five healthy volunteers--images created
      in 11 min with nominal resolution of 8.4 mm isotropic). However, residual
      intensity was observed in the ventricular space on triple-quantum-filtered images
      acquired with either optimized or standard parameters, contrary to the
      expectation of complete single-quantum signal suppression. Further simulation and
      experimentation suggest that this is likely due to the combination of triple
      quantum-passed signal from surrounding brain tissue being spatially smeared into
      the ventricular space and single-quantum-signal breakthrough from sodium nuclei
      in the fluid space. It is shown that the latter can be eliminated with judicious
      first flip angle selection.

PMID- 21956284
TI  - Sensitivity analysis of reaction-diffusion constraints in muscle energetics.
AB  - Theoretical and experimental studies of aerobic metabolism on a wide range of
      skeletal muscle fibers have shown that while all fibers normally function within
      the reaction control regime, some fibers operate near the transition region where
      reaction control switches to diffusion control. Thus, the transition region
      between reaction and diffusion control may define the limits of muscle function,
      and analysis of factors that affect this transition is therefore needed. In order
      to assess the role of all important model parameters, a sensitivity analysis (SA)
      was performed to define the parameter space where muscle fibers transition from
      reaction to diffusion control. SA, performed on a previously developed reaction
      diffusion model, shows that the maximum rate for the ATPase reaction
      (V(max,ATPase)), boundary oxygen concentration in the capillary supply (O 20),
      the mitochondrial volume fraction (epsilon(mito)), and the diffusion coefficient
      of oxygen (DO 2) are the most sensitive parameters affecting this transition to
      diffusion control. It is demonstrated that fibers are not limited by diffusion
      for slow reactions (V(max,ATPase)  < 25 mM/min), high oxygen supply for the
      capillaries (O 20 >= 35 uM), and large amounts of mitochondria (epsilon(mito) >=
      0.1). These conditions are applicable to muscle cells spanning a very broad range
      of animals. Within the diffusion-controlled region, the overall metabolic rate
      and ATP concentrations have much higher sensitivity to the diffusion coefficient
      of oxygen than to the diffusion coefficients of the other metabolites (ATP, ADP,
      P(i)).

PMID- 21956280
TI  - Clinical characteristics and prognosis of nontuberculous mycobacterial lung
      disease with different radiographic patterns.
AB  - RATIONALE: The clinical characteristics and prognostic impact of radiographic
      patterns of patients with nontuberculous mycobacterial lung disease (NTM-LD) are
      rarely evaluated. DESIGN: Patients with NTM-LD from 2007 to 2009 in a single
      medical center in Taiwan were identified. Their radiographic patterns were
      reviewed and classified into cavitary, bronchiectatic, or consolidative. They
      were also compared to patients with cavitary pulmonary tuberculosis (TB-LD).
      RESULTS: Of 481 NTM-LD patients identified, 62, 134, and 56 patients were
      categorized into cavitary, bronchiectatic, and consolidative groups,
      respectively. Compared with 180 TB-LD patients, cavitary NTM-LD had male
      predominance and was associated with higher grades of sputum acid-fast smear (3+
      or 4+), prior pulmonary TB, and poor baseline pulmonary function. NTM-LD patients
      with consolidative pattern were likely to have underlying comorbidity, the
      highest blood leukocyte count and C-reactive protein, and lowest albumin. In all
      NTM-LD, the consolidative pattern was independently associated with poor
      prognosis for 6-month survival. Patients with cavitary Mycobacterium avium
      complex (MAC)-LD had worse 6-month survival than those with bronchiectatic
      pattern. CONCLUSION: In Taiwan, NTM-LD patients with consolidative pattern have
      the worst prognosis while patients with cavitary pattern have worse survival than
      those with bronchiectasis in MAC-LD. Because varying radiographic patterns
      represent different prognoses, understanding the characteristics of NTM-LD
      patients with different radiographic patterns complements clinical practice.

PMID- 21956285
TI  - Structure and ultrastructure of spermatozoa and spermiogenesis in three species
      of Lucilia Robineau-desvoidy, 1830 (Diptera: Calliphoridae).
AB  - Morphology of male internal reproductive organs, spermatozoa, and spermiogenesis
      of the blow-flies Lucilia cuprina, Lucilia eximia, and Lucilia peruviana is first
      described here, using light and transmission electron microscopy. Spermiogenesis
      follows the characteristics described for others insect species. The spermatozoa
      of L. cuprina are similar to those described for other Brachycera. However, in L.
      eximia and L. peruviana, some differences were found. In L. cuprina and L. eximia
      species, the spermatozoa are long and thin, measuring about 211 MUm and 146 MUm
      in length, of which the head region measures approximately 19 MUm and 17 MUm,
      respectively. A polymorphism was observed in L. cuprina and L. eximia
      spermatozoa. In all three species, the head includes a monolayered acrosome with
      electron-lucent material. The shape of the nucleus, in cross sections, varies
      from circular to oval with completely condensed chromatin. Implantation of the
      axoneme was observed in the middle region of the nucleus, known as the "peg"
      region. In the next region, the beginning of two mitochondrial derivatives of
      similar diameter and different lengths in L. cuprina and only one in L. eximia
      and L. peruviana was observed. In the overlap region, the following structures
      were observed: nucleus, centriolar adjunct, mitochondrial derivatives, and
      axoneme. The axoneme is of a conventional insectan type with a 9 + 9 + 2
      microtubular arrangement. The male internal reproductive tract consists of
      testis, deferent ducts, a strongly developed seminal vesicle, accessory glands,
      and ejaculatory duct. These features are consistent with the structural diversity
      of the dipteran reproductive tract and spermatozoa, comprising an essential tool
      for understanding the complex variations found in the Diptera.

PMID- 21956286
TI  - Experimental and computational exploration of the dynamic behavior of (PNP)BF2, a
      boron compound supported by an amido/bis(phosphine) pincer ligand.
AB  - The diarylamido/bis(phosphine) PNP pincer ligand (2-(i)Pr(2)P-4-MeC(6)H(3))(2)N
      has been evaluated as a scaffold for supporting a BF(2) fragment. Compound
      (PNP)BF(2) (6) was prepared by simple metathesis of (PNP)Li (5) with Me(2)SBF(3).
      NMR spectra of 6 in solution are of apparent C(2) symmetry, suggestive of a
      symmetric environment about boron. However, a combination of X-ray structural
      studies, low-temperature NMR investigations, and DFT calculations consistently
      establish that the ground state of this molecule contains a classical four
      coordinate boron with a PNBF(2) coordination environment, with one phosphine
      donor in PNP remaining "free". Fortuitous formation of a single crystal of
      (PNP)BF(2).HBF(4) (7), in which the "free" phosphine is protonated, furnished
      another structure containing the same PNBF(2) environment about boron for
      comparison and the two PNBF(2) environments in 6 and 7 are virtually identical.
      DFT studies on several other diarylamido/bis(phosphine) pincer (PNP)BF(2) systems
      were carried out and all displayed a similar four coordinate PNBF(2) environment
      in the ground state structures. The symmetric appearance of the room-temperature
      NMR spectra is explained by the rapid interconversion between two degenerate four
      coordinate, C(1)-symmetric ground-state forms. Lineshape analysis of the (1)H and
      (19)F NMR spectra over a temperature range of 180-243 K yielded the activation
      parameters DeltaH(?) = 8.1(3) kcal mol(-1) and DeltaS(?) = -6.0(15) eu, which are
      broadly consistent with the calculated values. Calculations indicate that the
      exchange of phosphine donors at the boron center proceeds by an intrinsically
      dissociative mechanism.

PMID- 21956287
TI  - Whispering dysphonia in an Australian family (DYT4): a clinical and genetic
      reappraisal.
AB  - The designation, DYT4, was assigned to an Australian family with whispering
      dysphonia. The role of known causes of dystonia has not been comprehensively
      investigated in this family, nor has the possible relationship with Wilson
      disease (WND) in 2 siblings. Eighteen family members were neurologically
      examined, and DNA samples were obtained. Linkage analysis was performed to DYT1,
      DYT6, DYT7, DYT11, DYT13, DYT15, and ATP7B with microsatellite markers and the
      THAP1 (DYT6), PRKRA (DYT16), and ATP7B (WND) genes were sequenced. Reevaluation
      of the family identified 9 living affected family members, 6 of whom are newly
      affected. Phenotypic expression was variable, ranging from isolated spasmodic
      dysphonia (often with mild craniocervical dystonia) to severe generalized
      dystonia. Two newly described features included an extrusional tongue dystonia
      and a unique "hobby horse gait." Genetic analyses excluded all tested loci.
      Haplotype analysis of the ATP7B region resulted in three different combinations
      of the two parental alleles in the 8 investigated siblings of the 2 deceased WND
      patients, indicating that the fourth combination (of two mutated alleles) had
      occurred only in the deceased WND patients. On these two alleles, we identified a
      missense (c.2297C>G; p.T766R) and a splice-site mutation (IVS5+1G>T). The
      c.2297C>G mutation was detected in 3 affected and 4 unaffected family members,
      whereas the IVS5+1G>T mutation was detected in 1 affected and unaffected family
      member. Five DYT4 patients carried neither mutation. DYT4 is a familial form of
      dystonia unrelated to known dystonia genes and loci. ATP7B mutations do not
      segregate with the dystonia phenotype, indicating two independent genetic
      diseases in this family.

PMID- 21956289
TI  - Blackened names.

PMID- 21956288
TI  - Platelet decline as a predictor of brain injury in HIV infection.
AB  - An association between platelet decline and increased risk of progression to
      dementia has been observed in an advanced HIV infection cohort study. This
      investigation evaluated the prognostic significance of platelet decline for
      dementia, for psychomotor slowing, and for brain injury, as quantified in vivo,
      in a much larger population of HIV+ men. Platelet counts and neurocognitive data
      were available from biannual visits of 2,125 HIV+ men participating in the
      prospective, Multicenter AIDS Cohort Study from 1984 to 2009. Brain volumetric
      data were also available from an imaging substudy of 83 seropositive participants
      aged 50 and older. The association of platelet counts with neurocognitive outcome
      was assessed using Cox proportional hazard models where change in platelet count
      from baseline was a time-updated variable. Marked platelet decline was associated
      with increased risk of dementia in univariate analysis (hazard ratio [HR] = 2.5,
      95% confidence interval [CI] = 1.8-3.5), but not after adjustment for CD4 cell
      count, HIV viral load, age, study site, hemoglobin, race, education, smoking, and
      alcohol use (HR = 1.4, 95% CI = 0.78-2.5). Platelet decline did not predict
      psychomotor slowing in either univariate (HR = 0.79, 95% CI = 0.58-1.08) or
      multivariate (HR = 1.10, 95% CI = 0.73-1.67) analysis. Analysis of brain
      volumetric data, however, indicated a relationship between platelet decline and
      reduced gray matter volume fraction in univariate (p = 0.06) and multivariate (p
      < 0.05) analyses. Platelet decline was not an independent predictor of dementia
      or psychomotor slowing, after adjusting for stage of disease. Findings from a
      structural brain imaging substudy of older participants, however, support a
      possible relationship between platelet decline and reduced gray matter.

PMID- 21956291
TI  - Heritage threats.

PMID- 21956290
TI  - One up, one down.

PMID- 21956292
TI  - Why animal research needs to improve.

PMID- 21956304
TI  - Clean-energy credits tarnished.

PMID- 21956305
TI  - Europe to map the human epigenome.

PMID- 21956306
TI  - Vaccine campaign to target deadly childhood diarrhoea.

PMID- 21956307
TI  - Speedy neutrinos challenge physicists.

PMID- 21956308
TI  - 'Patent trolls' target biotechnology firms.

PMID- 21956309
TI  - Aboriginal genome analysis comes to grips with ethics.

PMID- 21956310
TI  - America recovers: stimulus-response.

PMID- 21956311
TI  - Translational research: 4 ways to fix the clinical trial.

PMID- 21956312
TI  - More time for research: fund people not projects.

PMID- 21956313
TI  - Policy: time to legislate for the good life.

PMID- 21956318
TI  - Administrative burdens: bureaucracy savings should go to research.

PMID- 21956319
TI  - Academic autonomy: more freedom for Turkish science.

PMID- 21956320
TI  - Ireland: a strong knowledge economy.

PMID- 21956321
TI  - Ireland: global links pay off.

PMID- 21956322
TI  - Structural biology: snapshot of a signalling complex.

PMID- 21956323
TI  - Cosmology: gravity tested on large scales.

PMID- 21956325
TI  - Climate science: ocean dynamics not required?

PMID- 21956324
TI  - Immunology: recognition of a unique partner.

PMID- 21956327
TI  - Cardiovascular biology: heart fails without pump partner.

PMID- 21956328
TI  - Carbon cycle: a dent in carbon's gold standard.

PMID- 21956329
TI  - Gravitational redshift of galaxies in clusters as predicted by general
      relativity.
AB  - The theoretical framework of cosmology is mainly defined by gravity, of which
      general relativity is the current model. Recent tests of general relativity
      within the Lambda Cold Dark Matter (LambdaCDM) model have found a concordance
      between predictions and the observations of the growth rate and clustering of the
      cosmic web. General relativity has not hitherto been tested on cosmological
      scales independently of the assumptions of the LambdaCDM model. Here we report an
      observation of the gravitational redshift of light coming from galaxies in
      clusters at the 99 per cent confidence level, based on archival data. Our
      measurement agrees with the predictions of general relativity and its
      modification created to explain cosmic acceleration without the need for dark
      energy (the f(R) theory), but is inconsistent with alternative models designed to
      avoid the presence of dark matter.

PMID- 21956330
TI  - Interannual variability in the oxygen isotopes of atmospheric CO2 driven by El
      Nino.
AB  - The stable isotope ratios of atmospheric CO(2) ((18)O/(16)O and (13)C/(12)C) have
      been monitored since 1977 to improve our understanding of the global carbon
      cycle, because biosphere-atmosphere exchange fluxes affect the different atomic
      masses in a measurable way. Interpreting the (18)O/(16)O variability has proved
      difficult, however, because oxygen isotopes in CO(2) are influenced by both the
      carbon cycle and the water cycle. Previous attention focused on the decreasing
      (18)O/(16)O ratio in the 1990s, observed by the global Cooperative Air Sampling
      Network of the US National Oceanic and Atmospheric Administration Earth System
      Research Laboratory. This decrease was attributed variously to a number of
      processes including an increase in Northern Hemisphere soil respiration; a global
      increase in C(4) crops at the expense of C(3) forests; and environmental
      conditions, such as atmospheric turbulence and solar radiation, that affect CO(2)
      exchange between leaves and the atmosphere. Here we present 30 years' worth of
      data on (18)O/(16)O in CO(2) from the Scripps Institution of Oceanography global
      flask network and show that the interannual variability is strongly related to
      the El Nino/Southern Oscillation. We suggest that the redistribution of moisture
      and rainfall in the tropics during an El Nino increases the (18)O/(16)O ratio of
      precipitation and plant water, and that this signal is then passed on to
      atmospheric CO(2) by biosphere-atmosphere gas exchange. We show how the decay
      time of the El Nino anomaly in this data set can be useful in constraining global
      gross primary production. Our analysis shows a rapid recovery from El Nino
      events, implying a shorter cycling time of CO(2) with respect to the terrestrial
      biosphere and oceans than previously estimated. Our analysis suggests that
      current estimates of global gross primary production, of 120 petagrams of carbon
      per year, may be too low, and that a best guess of 150-175 petagrams of carbon
      per year better reflects the observed rapid cycling of CO(2). Although still
      tentative, such a revision would present a new benchmark by which to evaluate
      global biospheric carbon cycling models.

PMID- 21956333
TI  - Can algal uptake stop NO3(-) pollution?

PMID- 21956335
TI  - Chemical characteristics of aerosols and trace gas distribution over North and
      Central India.
AB  - A field campaign on aerosol chemical properties and trace gases measurements was
      carried out along the Delhi-Hyderabad-Delhi road corridor (spanning about 3,200
      km) in India, during February 1-29, 2004. Aerosol particles were collected on
      quartz and cellulose filters using high volume (PM(10)) sampler at various
      locations along the route (i.e., urban, semi-urban, rural, and forest areas) and
      have been characterized for major cations (Na(+), Ca(2+), Mg(2+), K(+), and NH
      (4) (+)), anions (Cl(-), NO (3)(-), and SO (4)(2-)), and heavy metals (Cu, Cd,
      Fe, Zn, Mn, and Pb). Simultaneously, we measured NO(2) and SO(2) gases. These
      species show large spatial and temporal variations. The ambient PM(10)
      concentration has been observed to be the highest (55 +/- 4 MUg m(-3)) near semi
      urban areas followed by forest areas (48 +/- 2 MUg m(-3)) and in rural areas (44
      +/- 22 MUg m(-3)). The concentrations of NO( x ) (NO(2)+NO) and SO(2) ranged from
      16 to 69 MUg m(-3) and 4 to 11 MUg m(-3), respectively. Among anions, NO(3)(-)
      and SO(4) (2-) are the major constituents of PM(10). The urban and semi-urban
      sites showed enhanced concentrations of Fe, Zn, Mn, Cd, and Pb. This study
      provide information about atmospheric concentrations of various species in the
      northern to central India, which may be important for policy makers to better
      understand the air quality of the region.

PMID- 21956331
TI  - Conformational changes in the G protein Gs induced by the beta2 adrenergic
      receptor.
AB  - G protein-coupled receptors represent the largest family of membrane receptors
      that instigate signalling through nucleotide exchange on heterotrimeric G
      proteins. Nucleotide exchange, or more precisely, GDP dissociation from the G
      protein alpha-subunit, is the key step towards G protein activation and
      initiation of downstream signalling cascades. Despite a wealth of biochemical and
      biophysical studies on inactive and active conformations of several
      heterotrimeric G proteins, the molecular underpinnings of G protein activation
      remain elusive. To characterize this mechanism, we applied peptide amide hydrogen
      deuterium exchange mass spectrometry to probe changes in the structure of the
      heterotrimeric bovine G protein, Gs (the stimulatory G protein for adenylyl
      cyclase) on formation of a complex with agonist-bound human beta(2) adrenergic
      receptor (beta(2)AR). Here we report structural links between the receptor
      binding surface and the nucleotide-binding pocket of Gs that undergo higher
      levels of hydrogen-deuterium exchange than would be predicted from the crystal
      structure of the beta(2)AR-Gs complex. Together with X-ray crystallographic and
      electron microscopic data of the beta(2)AR-Gs complex (from refs 2, 3), we
      provide a rationale for a mechanism of nucleotide exchange, whereby the receptor
      perturbs the structure of the amino-terminal region of the alpha-subunit of Gs
      and consequently alters the 'P-loop' that binds the beta-phosphate in GDP. As
      with the Ras family of small-molecular-weight G proteins, P-loop stabilization
      and beta-phosphate coordination are key determinants of GDP (and GTP) binding
      affinity.

PMID- 21956336
TI  - Eutrophication and environmental policy in the Mediterranean Sea: a review.
AB  - The Mediterranean Sea is a semienclosed basin connected with the open sea mainly
      through the Strait of Gibraltar. Due to the circulation pattern and the long
      residence time ranging between 80 and 100 years, the Mediterranean Sea is a
      sensitive environment to eutrophication pressures. The main body of water of the
      Mediterranean is characterized by very low nutrient concentrations, and
      therefore, the Mediterranean is classified among the most oligotrophic (very poor
      waters in nutrients) seas of the world's oceans. However, some coastal areas,
      mainly in the northern part of the basin, receive excessive loads of nutrients
      from sewage effluents, river fluxes, aquaculture farms, fertilizers, and
      industrial facilities, showing intense eutrophic phenomena with many adverse
      effects for the marine ecosystem and humans. Various national and international
      authorities, in addition to monitoring, have taken legal and administrative
      measures to mitigate eutrophication trends in the area. The Mediterranean
      environment is a good paradigm of integration of extensive legal framework,
      scientific knowledge, and administrative practices. The Barcelona Convention, the
      Mediterranean Action Plan, and European Union Directives on water quality and
      coastal management, together with scientific information derived from
      international research programs in the Mediterranean, provide a sound background
      for practical actions in eutrophication problems. In the present work, the
      problem of coastal eutrophication in the Mediterranean is reviewed in connection
      with public policies of the Mediterranean States based on national and
      international legislation and scientific knowledge on Mediterranean oceanography
      ecology and actions coordinated by international bodies. These common actions and
      practices on coastal management are also discussed in relation to the need for
      sustainable development and protection of the coastal zone in the Mediterranean
      Sea.

PMID- 21956337
TI  - Characterization of organic chemical contaminants in sediments from Jobos Bay,
      Puerto Rico.
AB  - Jobos Bay, located on the southeastern coast of Puerto Rico, contains a variety
      of habitats including mangroves, seagrass meadows, and coral reefs. The watershed
      surrounding the bay includes a number of towns, agricultural areas, and the Jobos
      Bay National Estuarine Research Reserve (NERR). Jobos Bay and the surrounding
      watershed are part of a Conservation Effects Assessment Project (CEAP), involving
      the Jobos Bay NERR, the US Department of Agriculture, and the National Oceanic
      and Atmospheric Administration (NOAA) to assess the benefits of agricultural best
      management practices (BMPs) on the terrestrial and marine environments. As part
      of the Jobos Bay CEAP, NOAA collected sediment samples in May 2008 to
      characterize over 130 organic chemical contaminants. This paper presents the
      results of the organic contaminant analysis. The organic contaminants detected in
      the sediments included polycyclic aromatic hydrocarbons (PAHs), polychlorinated
      biphenyls, and the pesticide DDT. PAHs at one site in the inner bay near a boat
      yard were significantly elevated; however, all organic contaminant classes
      measured were below NOAA sediment quality guidelines that would have indicated
      that impacts were likely. The results of this work provide an important baseline
      assessment of the marine environment that will assist in understanding the
      benefits of implementing BMPs on water quality in Jobos Bay.

PMID- 21956338
TI  - Heavy metal distribution and enrichment in sediments of Mejillones Bay (23
      degrees  S), Chile: a spatial and temporal approach.
AB  - Concentrations of Ni, Cd, Pb, Cu, and Zn were measured in the surface sediments
      of Mejillones Bay at 32 sites ranging in depth from 10 to 95 m. A similarity
      dendrogram analysis separated the study area into two large sedimentary facies: a
      coastal zone with low metal concentrations and a deep zone with high metal
      concentrations. The abundances of Zn, Ni, and Pb increased between two sampling
      periods (5 years apart) in association with greater anthropogenic activity along
      the coastline of the bay at the present. The results were analyzed with the index
      of geoaccumulation and by applying the sediment quality guideline. Although
      similar to preindustrial levels, current Cu and Ni concentrations pose a likely
      threat to communities of benthic organisms. Concentrations of Zn and Pb are
      enriched, probably in connection with the industrial development of the zone, but
      do not reach dangerous levels for the benthic communities. Cd concentrations are
      toxic to benthic life, even though those measured herein are similar to
      preindustrial levels. Thus, these Cd levels are a result of the bay's natural
      characteristics (e.g., high biological productivity, the microxic water-sediment
      interface). The results of the Chilean aquatic sediment quality standards and the
      international standard (sediment quality guideline) were similar but differed
      from those found using the index of geoaccumulation, which suggests that the
      proposed reference values for Chilean aquatic sediment should be reviewed.

PMID- 21956339
TI  - The return periods and risk assessment of severe dust storms in Inner Mongolia
      with consideration of the main contributing factors.
AB  - This study presents a methodology for return period analysis and risk assessment
      of severe dust storm disaster. Meteorological observation data, soil moisture
      data, and remote sensing data from 30 meteorological stations in Inner Mongolia
      (western China) from 1985 to 2006 were used for the study. A composite index of
      severe dust storm disaster (Index I (SDS)) based on the influence mechanisms of
      the main contributing factors was developed by using the analytic hierarchy
      process and the weighted comprehensive method, and the hazard risk curves (i.e.,
      the transcendental probability curves of I (SDS)) for the 30 stations were
      established using the parameter estimation method. We then analyzed the risk of
      the occurrence of severe dust storm under different scenarios of 5-, 10-, 20-,
      and 50-year return periods. The results show that the risk decreased from west to
      east across Inner Mongolia, and there are four severe dust storm occurrence peak
      value centers, including Guaizihu, Jilantai, Hailisu, and Zhurihe-Erenhot. The
      severity of dust storms in seven places will be intolerable in the 50-year return
      period scenario and in three places in the 20-year return period scenario. These
      results indicate that these locations should concentrate forces on disaster
      prevention, monitoring, and early warning. The I (SDS) was developed as an easily
      understandable tool useful for the assessment and comparison of the relative risk
      of severe dust storm disasters in different areas. The risk assessment was
      specifically intended to support local and national government agencies in their
      management of severe dust storm disasters in their efforts to (1) make resource
      allocation decisions, (2) make high-level planning decisions, and (3) raise
      public awareness of severe dust storm risk.

PMID- 21956340
TI  - Can fish gill anomalies be used to assess water quality in freshwater neotropical
      systems?
AB  - Gill anomalies in two fish species (Geophagus brasiliensis and Astyanax
      bimaculatus) were compared among three freshwater systems with different water
      quality: one eutrophic river, one eutrophic reservoir, and one oligotrophic
      reservoir. The raised hypotheses are that reservoirs with low water quality
      (eutrophic) have fish with more gills anomalies compared with reservoirs with
      high water quality (oligotrophic), and that the more stable environmental
      conditions of eutrophic rivers have fish with better healthy conditions than
      eutrophic reservoirs that have lesser stable environmental conditions. Gills of
      36 adult individuals of G. brasiliensis and 23 of A. bimaculatus collected during
      the winter 2008 and winter 2009 were examined, and the proportions of occurrence
      of nine histological alterations were compared for the two species among the
      three systems using a binomial t test for independent samples. Histological
      changes in fish gills that are reversible and unspecific, such as epithelial
      lifting, interstitial edema, leukocyte infiltration, hyperplasia of the
      epithelial cells, lamellar fusion, and vasodilatation were common in both fish
      species in the three systems. However, lamellar aneurism, which is a more serious
      and often irreversible anomaly, and lamellar blood congestion occurred only in
      fish from the two reservoirs. Alternatively, necrosis occurred more in fish from
      the river. Fish gill anomalies in both species did not differ between the two
      reservoirs, despite having different water quality. We rejected the hypothesis
      that reservoirs with lower water quality have fish with more gill injuries
      compared with high water quality reservoirs. Moreover, the eutrophic river seems
      to affect differently the healthy condition of fish species, compared with the
      eutrophic reservoir.

PMID- 21956341
TI  - Environmental influence on coastal phytoplankton and zooplankton diversity: a
      multivariate statistical model analysis.
AB  - In a marine ecosystem, the diversity of phytoplankton can influence the diversity
      of zooplankton, or vice versa, and both can be affected by the environmental
      factors. In this study, we used principal component analysis (PCA) to identify
      the major sources of influence on the coastal water near an industrial park,
      following by construction of structural equation model (SEM) to determine the
      direct and indirect effect of the factors on phytoplankton and zooplankton
      diversity. PCA results indicated that the coastal area was mainly affected by
      riverine discharge (represented by high PC factor loadings of transparency and
      turbidity) and seasonal change (represented by temperature). SEM further
      suggested that both riverine discharge and seasonal influences can directly
      affect phytoplankton diversity, but indirectly affected zooplankton diversity via
      changes in phytoplankton. Using PCA to determine the sources of influence
      followed by construction of SEM allowed us to understand the relative importance
      of the environmental factors, direct or indirect, on phytoplankton and
      zooplankton diversity. When environmental changes occur, a new SEM could be
      constructed using the same category of physical and biological data and then
      compared to the current model to verify whether the environmental changes were
      the cause of alterations in planktonic communities in the area.

PMID- 21956342
TI  - The effects of water diversion and climate change on hydrological alteration and
      temperature regime of karst rivers in central Croatia.
AB  - Karst rivers in Croatia have been heavily dammed in the past. However, long-term
      impacts of dams, water diversion and climate change on karst rivers in Croatia
      have rarely been examined. This study analyzes long-term trends of hydrological
      and temperature conditions, prior to closure of new large dam, in five connected
      karst rivers of central Croatia: the sinking rivers Gornja Dobra and Zagorska
      Mreznica that have underground connections with the Gojacka Dobra, Tounjcica and
      Mreznica Rivers. It was established that hydrological conditions of these rivers
      have been greatly changed after the Gojak HPP, located at spring of Gojacka
      Dobra, became operational in 1959. Water diversion from the reservoirs on
      Zagorska Mreznica and Gornja Dobra to the Gojak HPP has increased mean annual
      discharge (52-106%), causing great subdaily fluctuations and overall modification
      of natural flow regime along the whole course of Gojacka Dobra. By cutting the
      connection between Zagorska Mreznica and Tounjcica, water diversion has caused a
      reduction of mean annual discharges of the Tounjcica (-60%) and Mreznica (-29%)
      Rivers. Analyses of long-term trends in water temperature over the last 50 years
      have revealed significant positive trends in average annual temperature at three
      gauging stations on three rivers with increase of 0.17, 0.44 and 0.48 degrees C
      per decade and climate change as the primary cause. The highest significant
      increasing trend was established at the lower course of Mreznica where discharge
      was reduced by water diversion. Mitigation measures for the improvement of
      hydrological conditions of affected rivers and underground systems are proposed
      and discussed.

PMID- 21956343
TI  - Spatially modulating interfacial properties of transparent conductive oxides:
      patterning work function with phosphonic Acid self-assembled monolayers.
AB  - The interface between an organic semiconductor and a transparent conducting oxide
      is crucial to the performance of organic optoelectronics. We use microcontact
      printing to pattern pentafluorobenzyl phosphonic acid self-assembled monolayers
      (SAMs) on indium tin oxide (ITO). We obtain high-fidelity patterns with sharply
      defined edges and with large work function contrast (comparable to that obtained
      from phosphonic acid SAMs deposited from solution).

PMID- 21956344
TI  - Does addition of antiviral medication to high-dose corticosteroid therapy improve
      hearing recovery following idiopathic sudden sensorineural hearing loss?

PMID- 21956345
TI  - Palladium-catalyzed pentannulation of polycyclic aromatic hydrocarbons.
AB  - We present a new and versatile one-step synthesis of a series of small molecular
      chromophores based on cyclopentannulated polycyclic aromatic hydrocarbons (PAH).
      Easily available pyrene, anthracene, and perylene bromides serve as starting
      materials for the reactions. The formation of the five-membered ring is achieved
      by the straightforward palladium(0)-catalyzed carbannulation with various
      substituted acetylenes. This approach is applicable either to single or multiple
      annulation procedures leading to hitherto inaccessible PAH topologies. According
      to the resulting products of the diverse reactions, a mechanistic explanation is
      proposed. UV/Vis absorption as well as cyclovoltammetric measurements were
      performed for characterization demonstrating the value of this annulation
      technique. Optical absorptions of up to 780 nm and absorption coefficients
      ranging from 8000 to 34,000 M(-1) cm(-1) were detected.

PMID- 21956346
TI  - Pipeline in clinical practice in 2011.

PMID- 21956347
TI  - Dehydrogenation processes via C-H activation within alkylphosphines.
AB  - Phosphines are commonly used in organometallic chemistry and are present in a
      wide variety of catalytic systems. This feature article highlights the advances
      made in dehydrogenation processes occurring within alkylphosphines, with the aim
      of further developing catalytic processes involving C-H activation together with
      potential applications in the field of hydrogen storage.

PMID- 21956348
TI  - Management of peri-implant soft tissues between tooth and adjacent immediate
      implant placed into fresh extraction single socket: a one-year prospective study
      on two different types of implant-abutment connection design.
AB  - AIM: This prospective study has been designed to evaluate the correlation between
      the presence/absence of the interproximal papilla and the mesio-distal and corono
      apical position single-tooth replacement implants inserted immediately following
      tooth extraction. These distances have been evaluated measuring the horizontal
      distance between the implant and the adjacent tooth (implant tooth distance, ITD)
      and the vertical distance between the contact point and the coronal margin of the
      interproximal bone (contact point-bone distance, CPB). METHODS: Fifty implants
      (25 Astratech(r) straight and 25 Straumann(r)) immediately placed after tooth
      extraction in highly aesthetic areas have been evaluated by means of clinical and
      radiographic evaluation. Gingival index (GI) and the presence/absence of the
      interproximal papilla were clinically measured. A computerized analysis was
      performed to determine ITD and CPB values after converting perioapical
      radiographs to digitalized images. were performed to determine: the effect of ITD
      and CPB on the presence or absence of the interproximal papilla was studied by
      statistical analysis. RESULTS: The gingival index was 0 in 97% of the areas and 1
      in 3%. When ITD was 2.5 to 4 mm, the interproximal papilla was significantly
      present (P<0.05). CPB of 3 to 5 mm was related (P<0.05) to the papilla presence
      if ITD was 2.5 to 4 mm, and this finding was valid for Astratech implants only.
      CONCLUSION: The horizontal distance of 2.5 to 4 mm between an implant and the
      adjacent tooth is significantly associated to a full interproximal papilla.

PMID- 21956349
TI  - The treatment of the large periradicular endodontic injury.
AB  - AIM: Periradicular lesions of endodontic origin are characterized by
      polymicrobial infections, part of which appear to play a crucial role in the
      facultative anaerobic bacterical species. In literature there is a strong
      disagreement about the choice of treatment in large periradicular lesions of
      endodontic origin: some authors propose the orthograde root canal therapy, others
      surgical therapy with apicectomia, retrograde filling of the cavity and review
      instrument. The purpose of this study was to demonstrate the effectiveness of
      orthograde endodontic treatment in case of periapical lesions of endodontic
      origin of dimensions larger than 20 mm. METHODS: It was evaluated a sample of 60
      cases, ages between 18 and 70 years, 32 men and 28 women. The cases have been
      treated by orthograde endodontic. Were included mono and pluriradicular teeth
      with periapical lesion of endodontic origin primary or secondary at endodontic
      incongruous treatment, with dimensions larger than 20 mm. The sample was divided
      into Group A: 19 cases in which was possible to complete the root canal therapy
      in the same event; Group B: 41 cases in which there was drainage. Dressing was
      applied with pure calcium hydroxide, which was renewed every 10 days for a
      maximum of 30, was eventually completed the endodontic therapy. RESULTS: Group A:
      13 out of 19 cases showed healing at 5 years. Of the remaining 6, there were
      three failures, a crown-root fracture, missed two follow-up. At 10 years of the
      13 successes, 2 cases showed relapse. Group B: 41 cases, later reduced to 30 we
      had 19 successes in 5 years. Of the remaining 11: 3 crown-root fractures, 2
      missed the follow-up, 6 failures. At 10 years of the 19 successes, two were lost
      because of fracture, one for a relapse. Discussion. The results show the
      importance of drainage, which can affect the apical seal and therefore the
      success of endodontic therapy, but allows decompression of the periradicular
      lesion and symptoms regression. The use of calcium hydroxide in the intermediary
      dressings allows the neutralization of acidic compounds, alkaline phosphatase
      activation creating a significant development of the antibacterial action. Proper
      instrumentation and cleansing of root canals allows the reduction of over one
      thousand times the bacterial load. The coronal seal has, through the adhesive
      techniques of restorative materials, a crucial role in closing the doors of entry
      the bacterial contamination of treated root canals. CONCLUSION: The endodontic
      therapy by orthograde is considered primary therapeutic choice in case of large
      endodontic lesions, given the success at rate both 5 (Group A 68,41%, Group B
      63,33%) and 10 years (Group A 57.88%, Group B 53.32%).

PMID- 21956350
TI  - Effect of silane coupling agents and alloy primers on adhesion to titanium.
AB  - AIM: Titanium-ceramic adhesion is known to be not ideal yielding to ceramic
      fractures especially in extensive implant reconstructions. Intraoral repair
      actions could be performed chairside using adhesion promoters. This study
      evaluated the adhesion of resin composite to titanium alloy using different
      silane coupling agents and alloy primers in combination with surface conditioning
      methods after aging. METHODS: Titanium alloy disks were embedded in PMMA and wet
      polished to 1200 grit silicon carbide abrasive. Silanes and alloy primers used in
      combination with surface conditioning methods were as follows: 1) Al2O3 (50 um)
      and Alloy Primer (Kuraray); 2) Al2O3 (50 um) and V-Primer (Sun Medical); 3) SiO2
      (30 um) and Silane (ESPE-Sil) (CoJet System, 3M ESPE); 4) Al2O3 (50 um) and
      Silane (ESPE-Sil); 5) Al2O3 (50 um) and Cesead II Opaque Primer (Kuraray); 6)
      Al2O3 (50 um) and Alloy Primer and Clearfil SE Bond Primer and Clearfil Porcelain
      Bond Activator (Clearfil Repair System, Kuraray). A thin layer of Sinfony opaquer
      was then applied, polymerized and a direct resin composite (Quadrant
      Photoposterior, Cavex) was adhered onto the conditioned titranium surfaces using
      polyethylene molds. After thermocycling (6000 cycles at 5-55  degrees C),
      specimens were submitted to shear loading in the Universal Testing Machine
      (crosshead speed: 1 mm/min). Failure types were classified as adhesive, cohesive
      in resin and a combination of adhesive and cohesive failures (mixed) after
      debonding. The data (MPa) were analyzed statistically using One-way ANOVA and
      Tukey's tests. RESULTS: Significant difference was observed between the groups
      (P<0.05) (1-way ANOVA). Significantly higher results were obtained from Groups 1
      (25.4+/-7) and 6 (26.3+/-5) than those of other groups (11.4+/-3 - 22.6+/-9)
      (P<0.05) (Tukeys' test). Group 2 presented the lowest mean bond strength among
      all groups (11.4+/-3) (P<0.05). While Group 1 showed mainly cohesive (4 out of
      10) and mixed failures (6 out of 10) and no adhesive failures, other groups
      presented mainly adhesive and mixed failures. CONCLUSION: Conditioning titanium
      surfaces with 50 um Al2O3 followed by Alloy Primer or silane mixture of Clearfil
      Repair system delivered the most stable repair bond strength of the resin
      composite to titanium compared to other alloy primers and silanes tested.

PMID- 21956351
TI  - Pediatric sialolithiasis distinctive characteristic in radiological imaging.
AB  - AIM: Aim of the present paper was to investigate the imaging and related clinical
      characteristics of sialolithiasis in Italian pediatric population trying to
      determine the difference between pediatric and adult. METHODS: Twenty-nine
      pediatric patients (age range 1-17 years) with pain and postprandial swelling
      and/or purulent discharge in the salivary gland areas were referred to radiology
      department after pediatric ear, nose and throat (ENT) evaluation. They all were
      submitted to ultrasound examination of the main salivary glands. Multidetector
      computed tomography (MDCT) only was performed in 2/6 patients, in 2/6 patients
      both sialography and MDCT were performed due to inconclusive MDCT features, 2/6
      only sialography was performed. Sialoliths were classified on their location and
      size. RESULTS: In 6 out of 29 patients (4 males, 2 females, age range 1-17 years)
      salivary stones were detected. Sialoliths were detected in 5/6 patients in the
      submandibular gland and 1/6 in the parotid gland. All sialoliths, excepted for a
      case of multiple sialoliths, were located in the distal part of the main salivary
      ducts. CONCLUSION: Imaging characteristics of sialolith in pediatric group are
      similar than in adult population in few aspects. In fact sialoliths are smaller
      in size and located more frequently in the distal part of the main salivary duct,
      than in adult, making sialography cannulation more complex and requiring short
      thickness in MDCT.

PMID- 21956352
TI  - Scleroderma and CREST syndrome: a case report in dentistry.
AB  - CREST syndrome is part of the heterogeneous scleroderma group of autoimmune
      diseases that cause thickening, hardening and tightening of the connective tissue
      in different parts of the body, and it may lead to complex disorders. CREST
      syndrome is characterized by the coexistence of calcinosis, Raynaud's phenomenon,
      esophageal hypomotility, sclerodactily and telangectasia. A 72-year-old caucasian
      woman is referred to the S. Gerardo Hospital of Monza, with a chief complaint of
      oral pain and difficulties in deglutition and eating, associated with denture
      instability and difficulties to fit it. She had been previously diagnosed with
      Raynaud's phenomenon, and afterwards with CREST syndrome. Extra-oral examination
      underlined taut, thickened and rigid skin, pallid-red irregular maculae all over
      the face, telangiectasias and acrocyanosis. Intra-oral examination showed no
      alteration of the mucosa, but we can observe tongue rigidity and some speckled
      red alternating with white spots on the hard palate and in the vestibule. We
      undermitted the patient the dental treatment of Sjogren's syndrome. The
      management of the Sjogren's syndrome is symptomatic and empirical, and involves
      the use of saliva secretion stimulators, salivary substitutes and coadjuvants.
      Dental treatment and prophylaxis are important to prevent the consequences of
      xerostomia, such as rampant caries, based on the administration of topical
      fluoride in toothpastes and rinses, and supplemented by fluoride gels and
      varnishes. Instruction and reinforcement of oral hygiene, along with frequent
      dental assessment and management by the dentist are essential measures to
      preserve the oral health of those affected with CREST syndrome in progression to
      SS, complicated with Sjogren's syndrome.

PMID- 21956353
TI  - Preservation of an injured vital tooth using ultrasonic device and mineral
      trioxide aggregate.
AB  - The purpose of this case report is to present a root fracture repair procedure
      for non devitalized injured tooth. One injured, non-endodontically treated
      maxillary anterior tooth in which an incomplete vertical root fracture involving
      only the buccal side was suspected, underwent an exploratory flap to visualize
      the pattern of bone loss and assess the type of root fracture. The pre-operative
      diagnosis was confirmed. A groove following fracture line was prepared using
      retro-tips driven by an ultrasonic device and sealed with Mineral Trioxide
      Aggregate (MTA), following filling of the bone defect with Calcium Sulphate. At
      24 months follow up the case showed clinical and radiographic success. The
      present surgical approach showed preservation of function and vitality of tooth
      with a shallow incomplete vertical root fracture.

PMID- 21956354
TI  - Peripheral ameloblastoma: case report.
AB  - Ameloblastoma is a benign tumour of the odontogenic tissues which may be
      aggressive in the involved area with a high rate of recurrence if not adequately
      removed, and represents 1% of all tumours of the mouth, generally appearing in
      the bones of the jaw. Although it is fairly rare, tumours with such
      histopathology have been described in the soft tissue and are named peripheral or
      extraosseus ameloblastoma. Potential cells of origin are ondontogenic residue of
      the dental lamina, pluripotent cells in the basal layer of the epithelial mucosa,
      and pluripotent cells of the minor salivary glands. Seven cases of extraosseus
      ameloblastoma in the extragengival area, unrelated to dental germs, have been
      described, six of which in the buccal mucosa and one in the mouth floor. We
      report a case of extraossous, extragengival ameloblastoma which originated in the
      subzygomatic area.

PMID- 21956355
TI  - Inhibition of colon tumor growth by IL-15 immunogene therapy.
AB  - Interleukin-15 is a pleiotropic cytokine that has potential for cancer immunegene
      therapy. We previously reported the construction and characterization of IL-15
      overexpression vectors pHi2-IL15-CMV-tat (L1) and pHi2-spIL15-CMV-tat (L3), as
      well as carcinoembryonic antigen promoter-amplified IL-15 expression plasmid
      vectors pHi2-IL15-CEA-tat (L2) and pHi2-spIL15-CEA-tat (L4). In the current
      study, we evaluated the expression and therapeutic efficacy of these vectors
      using a mouse colon carcinoma model. Plasmid vectors were transfected into SW480
      and MCF-7 cells, and IL-15 overexpression was confirmed. IL-15 expressed by
      transfected tumor cells stimulated spleen cell proliferation in vitro.
      Intraperitoneal injection of plasmid pHi2-spIL15-CMV-tat (L3) into mice resulted
      in transgene expression by peritoneal mesothelial cells, inhibited CT-26 tumor
      growth and prolonged the survival of tumor-bearing mice. In addition, the in vivo
      transfection of plasmid pHi2-spIL15-CMV-tat (L3) via electroporation slowed the
      tumor formation of subcutaneously inoculated CT-26 cells. These data suggest that
      IL-15 overexpression achieves therapeutic effects in a mouse cancer model and
      that these gene transfer approaches should be further evaluated for use in the
      treatment of human cancers.

PMID- 21956356
TI  - Evaluation of the acute effects of distal coronary microembolization using
      multidetector computed tomography and magnetic resonance imaging.
AB  - The purpose of this study was to test the potential of clinical imaging
      modalities, 64-slice multidetector computed tomography (MDCT) and 1.5T magnetic
      resonance imaging (MRI) for qualitative and quantitative evaluation of acute
      microinfarcts and to determine the effects of <120 MUm microemboli on left
      ventricular function, perfusion, cardiac injury biomarkers, arrhythmia, and
      cellular and vascular structures. Under X-ray fluoroscopy, 40-120 MUm (16 mm(3) )
      microemboli were delivered to embolize the left anterior descending (LAD)
      coronary artery of nine pigs. MDCT/MRI were performed at 72 h in a single
      session. Microinfarcts were visible in six of nine animals on delayed contrast
      enhanced MDCT/MR images but measurable in all animals using semiautomated
      threshold methods. Other MDCT and MRI sequences demonstrated decline in left
      ventricular ejection fraction, regional strain and perfusion in visible and
      invisible microinfarcted regions. Microemboli caused significant elevation in
      cardiac injury enzymes and arrhythmias. Various sizes of microinfarcts appeared
      microscopically as distinct aggregates of macrophages replacing myocardium.
      Semiautomated threshold methods are necessary to measure and confirm/deny the
      presence of myocardial microinfarcts. This study offers support for alternative
      applications of MDCT/MRI in assessing clinical cases in which microemboli <120
      MUm escape protective devices during percutaneous coronary interventions.
      Although microembolization resulted in no mortality, it caused left ventricular
      dysfunction, perfusion deficit, cellular damage increase in cardiac injury
      enzymes, and arrhythmias.

PMID- 21956360
TI  - Sunitinib-induced hyperparathyroidism: a possible mechanism to altered bone
      homeostasis.
AB  - BACKGROUND: Sunitinib malate is an orally bioavailable tyrosine kinase inhibitor
      that is active against many tyrosine kinase receptors involving crucial pathways
      in both healthy tissues and malignant tissues. Because its use in clinical
      practice is quite recent, many of its possible side effects remain unknown. In
      this report, the authors describe the incidence of new-onset hyperparathyroidism
      in a cohort of patients with metastatic renal cell carcinoma who received
      treatment with sunitinib. METHODS: Twenty-six patients who received first-line
      sunitinib for metastatic renal cell carcinoma were enrolled in this study for a
      mineral and parathyroid function assessment. Plasma levels of intact parathyroid
      hormone; serum levels of calcium, phosphorus, 25-hydroxyvitamin D(3), and 1,25
      dihydrovitamin D(3); and urinary 24-hour calcium and phosphorus excretion all
      were measured in each patient. Biochemical evaluations were performed before the
      beginning of treatment and at the end of each sunitinib treatment period.
      RESULTS: Eighteen of 26 patients (69.2%) developed hyperparathyroidism with
      normal serum calcium levels, and 6 of them developed hypophosphatemia. Patients
      presented with a mean elevation of parathyroid hormone after 2.2 cycles of
      sunitinib. The levels of 25-OH vitamin D(3) were stable over the course of
      treatment, whereas 1,25-OH vitamin D(3) levels were increased in 5
      hyperparathyroid patients. Those who presenting with elevated parathyroid hormone
      levels had low or undetectable urinary calcium levels. Parathyroid hormone
      elevation usually persisted but did not progress during long-term therapy with
      sunitinib. Permanent treatment interruption resulted in a resolution of
      hyperparathyroidism. CONCLUSIONS: Hyperparathyroidism developed in an high
      percentage of patients on sunitinib. Therefore, the authors concluded that
      sunitinib may affect parathyroid function and bone mineral homeostasis, possibly
      resulting in abnormal bone remodeling.

PMID- 21956362
TI  - The -1123G>C variant of PTPN22 gene promoter is associated with latent autoimmune
      diabetes in adult Chinese Hans.
AB  - The protein tyrosine phosphatase non-receptor 22 (PTPN22) gene encodes for
      lymphoid protein tyrosine phosphatase. Recent studies demonstrated the
      association between the +1858T, -1123G>C variants of PTPN22 gene and type 1
      diabetes mellitus in Caucasian and Japanese populations. This study examined the
      relationship between the polymorphism of PTPN22 gene and latent autoimmune 1
      diabetes in adults (LADA) in Chinese Hans. We studied 229 adult Chinese patients
      with LADA (LADA group) and 210 healthy volunteers (control group). The -1123G>C
      and +1858C>T polymorphisms of PTPN22 gene were determined by PCR-restriction
      fragment length polymorphism method. Further, genotypic/allelic frequencies and
      clinical characteristics were compared between two groups. There was a
      significant difference of frequencies of the -1123G>C polymorphism between LADA
      and control groups (OR = 1.99, 95% CI = 1.24-3.2; P = 0.001). However, no
      significant differences in the +1858C>T genotypic (CC, CT) and allelic (C, T)
      frequencies were found. Furthermore, the frequencies of the -1123 GC, CC genotype
      in male patients with LADA were significantly higher compared with male healthy
      volunteers (OR = 1.65, 95% CI = 1.21-2.26; P = 0.005). The analysis of covariance
      demonstrated no difference between glycosylated hemoglobin, body mass index,
      duration of diabetes, C-peptide, and GAD-Ab titer between the group carrying
      GC/CC and the group without allele C. In conclusion, the -1123G>C promoter
      polymorphism of PTPN22 gene, but not the +1858C>T variant, is associated with
      LADA in adult Chinese Hans.

PMID- 21956361
TI  - Lumboperitoneal shunt for idiopathic intracranial hypertension: patients'
      selection and outcome.
AB  - Surgical treatment of idiopathic intracranial hypertension (IIH) includes
      cerebrospinal fluid (CSF) diversion procedures most commonly lumboperitoneal (LP)
      shunt. LP shunt addresses the cause of both headache and papilledema more
      directly by effecting a global reduction of intracranial pressure. Twenty-two
      cases were included in the study. All patients underwent clinical, imaging, and
      CSF manometry evaluations. All patients showed failure or noncompliance to
      medical treatment and necessitated placement of an LP shunt. Analysis of data was
      conducted and evaluation of outcome was assessed. Among 22 patients who underwent
      LP shunt placement for IIH, 16 (72.8%) patients had severe and fulminant opening
      CSF pressures with values of more than 400 mmH(2)O. Among this group, 19 (86.4%)
      patients reported recovery of their headache and 16 (72.7%) patients showed
      complete resolution of papilledema. Shunt complications included two (9%) cases
      of shunt infection that required shunt extraction and antibiotic therapy, and six
      (27%) cases of shunt obstruction that required shunt revision. Manometric
      predictors for surgical treatment of IIH may include severe and fulminant opening
      CSF pressures as well as poor manometric response to repeated lumbar taps.
      Lumboperitoneal shunt is easy and effective for treating intractable headaches
      and visual impairment associated with IIH. Its usefulness can be optimized by
      meticulous technical placement of the shunt guided by rigorous protocols for
      shunt procedures.

PMID- 21956364
TI  - Spectrum of fluorodeoxyglucose-positron emission tomography/computed tomography
      and magnetic resonance imaging findings of ovarian tumors.
AB  - The purpose of this article is to review fluorodeoxyglucose-positron emission
      tomography/computed tomography (FDG-PET/CT) and magnetic resonance imaging (MRI)
      findings in a variety of benign, malignant, and borderline malignant ovarian
      tumors. It is advantageous to become familiar with the wide variety of FDG-PET/CT
      findings of this entity. Benign ovarian tumors generally have faint uptake,
      whereas endometriomas, fibromas, and teratomas show mild to moderate uptake.
      Malignant ovarian tumors generally have intense uptake, whereas tumors with a
      small solid component often show minimal uptake.

PMID- 21956365
TI  - Rim-enhancing breast masses with smooth or spiculated margins on magnetic
      resonance imaging: histopathology and clinical significance.
AB  - Rim enhancement is defined as enhancement that is more pronounced at the
      periphery of a mass. It can have varying appearances, ranging from a thin pattern
      to one that is thicker. This internal enhancement characteristic is an
      established characteristic of malignant lesions. Additionally, the use of
      combined descriptors, especially internal enhancement characteristics and the
      associated margin, can provide a more powerful predictive value than that of
      individual descriptors. The margin assessment of rim-enhancing masses is
      important and can vary in appearance from smooth to spiculated. Moreover, rim
      enhancement may be dynamic in that it changes appearance during the dynamic
      phases of contrast- enhanced breast magnetic resonance imaging (ce-MRI), and this
      feature can lead to confusion in the correct application of this lexicon. Rim
      enhancing masses on ce-MRI are typically of two morphological types (i.e., a thin
      rim-enhancing mass with a smooth margin and a thick rim-enhancing mass with a
      spiculated margin). It is helpful to review and clarify the lexicon of rim
      enhancement using combined descriptors based on the pathological findings as
      doing so can help predict the likelihood of malignancy of ce-MRI lesions.

PMID- 21956366
TI  - Suppression of vascular endothelial growth factor via siRNA interference
      modulates the biological behavior of human nasopharyngeal carcinoma cells.
AB  - PURPOSE: The aim was to study the effect of vascular endothelial growth factor
      (VEGF) down-regulation by small interfering (si)RNA-mediated interference (RNAi)
      on the biological features of nasopharyngeal carcinoma cell line CNE-2. MATERIALS
      AND METHODS: The combined plasmids pU-siVEGF and pU-siCONT were transfected into
      CNE-2 cells with lipofectamine. The transfected cells were placed in fresh medium
      containing G418. Expression of VEGF mRNA and protein were measured by reverse
      transcriptase-polymerase chain reaction and Western blot, respectively. The
      transwell chamber model was employed to test the ability of cell invasion in
      vitro. The distribution of cell cycle phases was determined by flow cytometry.
      Cell survival was assessed by clonogenic assays. RESULTS: Both VEGF mRNA and
      protein expression were significantly decreased in the pU-siVEGF group compared
      with controls (P < 0.05). The cell cycle was arrested in the G(1) phase (P <
      0.05). A higher apoptotic ratio and lower invasion ability were seen in the pU
      siVEGF group. The D(0) (mean lethal dose) and SF(2) values were significantly
      lower than those in the control group (P < 0.05). CONCLUSION: Delivery of siRNA
      targeting VEGF seems efficient in down-regulating VEGF expression and diminishing
      the growth, proliferation, and invasiveness of CNE-2 cells. It also enhanced the
      sensitivity of CNE-2 cells to radiation.

PMID- 21956367
TI  - Evaluation of lumber nerve root compression using thin-slice thickness coronal
      magnetic resonance imaging: three-dimensional fat-suppressed multi-shot balanced
      non-steady-state free precession versus three-dimensional T1-weighted spoiled
      gradient-recalled echo.
AB  - PURPOSE: The aim of this study was to compare the three-dimensional fat
      suppressed balanced non-steady-state free precession (3D FS-nSSFP) sequence and
      the 3D T1-weighted spoiled gradient-recalled echo (3D T1-GRE) sequence for
      evaluating lumbar nerve root compression with continuous thin-slice coronal
      magnetic resonance (MR) images. MATERIALS AND METHODS: The institutional review
      board approved this study, and written informed consent was obtained from all 35
      patients. We optimized continuous 2.5-mm thick lumbar coronal images with 3D FS
      nSSFP and 3D T1-GRE. We calculated the contrast-to-noise ratio (CNR) for nerve
      roots and other structures on images with the two sequences. With knowledge of
      the final diagnosis, we assessed the visibility of nerve root compression on
      these images. RESULTS: The CNR values of nerve roots were significantly higher on
      images with 3D FS-nSSFP than on those with 3D T1-GRE. These continuous thin-slice
      coronal images facilitated visualization of nerve root compression in >91% of
      patients. There was no statistically significant difference between the two
      sequences in the detection of nerve root compression. CONCLUSION: Continuous thin
      slice coronal MR images using 3D FS-nSSFP and 3D T1-GRE sequences are sufficient
      to evaluate lumbar nerve root compression, and 3D FS-nSSFP is superior to 3D T1
      GRE for depiction of lumbar nerve roots.

PMID- 21956368
TI  - Dosimetric comparison of 2.5 mm vs. 3.0 mm leaf width micro-multileaf collimator
      based treatment systems for intracranial stereotactic radiosurgery using dynamic
      conformal arcs: implications for treatment planning.
AB  - PURPOSE: The objective of our study was to explore any significant dosimetric
      differences between different leaf width (3.0 mm vs. 2.5 mm) micro-multileaf
      collimator (mMLC)-based treatment systems for intracranial stereotactic
      radiosurgery using dynamic conformal arcs (DCAs). MATERIALS AND METHODS: The
      systems included a 3 mm leaf width mMLC (m3) mounted on a nondedicated linac, and
      the Novalis Tx system with an integrated 2.5 mm width mMLC (HD120). Thirty plans
      for brain metastases were replanned for both systems using a uniform method for
      target definition and treatment planning for baseline comparison. RESULTS: The
      target coverage values for the 80% isodose surface (IDS) and the D95 values in
      the HD120 plans were significantly lower than those for the m3 plans. The ratios
      of lower isodose volumes to the target for the HD120 were smaller than those for
      the m3. When a 1 mm leaf margin was added to the HD120 plans, these differences
      were reversed, but statistically significant differences were still observed.
      CONCLUSION: Significant dosimetric differences were observed between these
      systems. Different planning methods are required for the two systems to attain
      similar target coverage values with selected IDS, which can be achieved by
      adjusting the leaf margin with 0.1 mm increments or isocenter dose settings.

PMID- 21956369
TI  - Acoustic radiation force impulse elastography of the liver: can fat deposition in
      the liver affect the measurement of liver stiffness?
AB  - PURPOSE: The aim of this study was to compare acoustic radiation force impulse
      (ARFI) results between livers with and without fat deposition. MATERIALS AND
      METHODS: We studied 200 consecutive healthy individuals who underwent health
      checkups at our institution. The subjects were divided into three groups
      according to the echogenicity of the liver on ultrasonography (US) and the liver
      spleen attenuation ratio index (LSR) on computed tomography: normal liver group
      (n = 121, no evidence of bright liver on US and LSR > 1); fatty liver group (n =
      46, bright liver on US and LSR < 1); others (n = 33, inconclusive results).
      Subjects in the inconclusive group and those who consumed alcohol >5 days a week
      (n = 18) were excluded from the analysis. The velocities measured by ARFI in the
      normal and fatty liver groups were compared using the two one-sided test.
      RESULTS: The mean (SD) velocity measured in the normal and fatty liver groups
      were 1.03 (0.12) m/s and 1.02 (0.12) m/s, respectively. The ARFI results of the
      fatty liver group were similar to those of the normal liver group (P < 0.0001).
      CONCLUSION: This study suggested that fat deposition in the liver does not affect
      the liver stiffness measurement determined by ARFI.

PMID- 21956370
TI  - Paratracheal air cysts using low-dose screening chest computed tomography:
      clinical significance and imaging findings.
AB  - PURPOSE: The aim of this study was to evaluate the prevalence and clinical
      relevance of paratracheal air cysts in a general population who underwent low
      dose computed tomography (LDCT). MATERIALS AND METHODS: From July 2005 to March
      2008, a total of 2002 persons underwent LDCT and were included in the study. We
      retrospectively reviewed the chest CT images and analyzed the location, level,
      and size of the air cysts. We checked whether the cysts had communication with
      the trachea. Other abnormalities of the lung were noted. We evaluated whether the
      presence of paratracheal air cysts is associated with abnormal pulmonary
      function. RESULTS: In all, 75 persons (3.7%) had 77 paratracheal air cysts: 76
      (98.7%) at the right side and 36 (46.7%) at the level of the T2 vertebral body.
      The mean anteroposterior diameter of the paratracheal air cysts was 7.5 mm, and
      mean transverse diameter was 4.2 mm. Altogether, 26 paratracheal air cysts
      (33.8%) showed communication with the trachea. Only two persons had respiratory
      symptoms. Pulmonary function tests showed that five patients (6.7%) had an
      obstructive pattern. CONCLUSION: The paratracheal air cysts were mostly located
      at the right side of the trachea and at the thoracic inlet level. One-third had
      communication with the trachea. Paratracheal air cysts are not associated with
      respiratory symptoms or obstructive lung disease clinically or radiologically.

PMID- 21956372
TI  - Serial fetal magnetic resonance imaging of cloacal exstrophy.
AB  - Cloacal exstrophy (CE) is a rare congenital malformation involving the urinary,
      intestinal, and genital systems. We present a case of CE in which characteristic
      findings were detected at two serial fetal magnetic resonance imaging (MRI)
      sessions. At 18 weeks' gestation, the initial fetal MRI revealed a cystic mass
      protruding from the infra-umbilical abdominal wall. During fetal development, the
      cystic mass disappeared, and an omphalocele and heterogeneous soft tissue mass
      were recognized at 28 weeks' gestation. The bladder was not visualized on either
      examination. CE can be diagnosed by prenatal MRI, thereby permitting prenatal
      counseling and appropriate postnatal management.

PMID- 21956371
TI  - Effect of interval between transcatheter hepatic arterial embolization and
      radiofrequency ablation on ablated lesion size in a swine model.
AB  - PURPOSE: The aim of the study was to clarify the effect of the interval between
      transcatheter hepatic arterial embolization (TAE) with Lipiodol plus gelatin
      sponge particles and radiofrequency (RF) ablation on the extent of ablation.
      MATERIALS AND METHODS: Eight healthy swine were divided into four groups: RF
      ablation (ablation only), RF ablation immediately after TAE (immediate ablation),
      RF ablation 3 days after TAE (3-day ablation), and RF ablation 6 days after TAE
      (6-day ablation). Five ablated lesions were created in each swine (10 per group).
      A 2-cm expandable LeVeen needle electrode was used for RF ablation. Ablated
      lesions are composed of an outer reddish zone and an inner whitish zone. RESULTS:
      The average longest length of the major, intermediate, and minor axes and the
      volume in the immediate ablation, 3-day ablation, and 6-day ablation groups were
      significant longer and greater (1.52 and 1.52, 1.46 and 1.50, and 1.37 and 1.35
      times greater in the red zone and the whitish area, respectively) than those in
      the ablation-only group (P < 0.05/3). Accumulation of Lipiodol was still noted in
      the hepatic sinusoids in the 3-day and 6-day ablation groups. CONCLUSION: RF
      ablation delayed to 6 days following TAE produced larger ablation volumes than
      did RF ablation alone.

PMID- 21956373
TI  - Cystic hypersecretory ductal carcinoma of the breast: a rare cause of cystic
      breast mass.
AB  - We present the case of a surgically confirmed, invasive, cystic hypersecretory
      ductal carcinoma (CHDC) of the breast in a 43-year-old woman. The initial
      sonography showed a complex cyst, which required a core biopsy; however, the
      diagnosis was delayed as the patient refused to undergo the biopsy and the cyst
      decreased in size, as seen on follow-up sonography. Excision biopsy was
      performed, and invasive CHDC was diagnosed after regrowth of the cystic lesion.
      Meticulous sonographic evaluation of a cystic breast mass is always important,
      and pathology confirmation must be considered if the lesion shows features
      suspicious for malignancy, as a CHDC could be the cause of a cystic breast mass.

PMID- 21956374
TI  - Percutaneous transhepatic drainage of lung abscess through a diaphragmatic
      fistula caused by a penetrating liver abscess.
AB  - Liver abscesses occurring just below the diaphragm can penetrate or perforate the
      thoracic cavity, resulting in lung abscess or pyothorax. Although surgical or
      percutaneous transpleural drainage is often required in such cases, the latter
      approach has some risks, including hemothorax and bronchopleural fistula
      formation when the cavity is surrounded by normal lung parenchyma. The present
      report describes a treatment technique of percutaneous transhepatic drainage
      through the diaphragmatic fistula to avoid the risks of a transpulmonary approach
      in a case of lung abscess caused by a penetrating liver abscess.

PMID- 21956375
TI  - Three-dimensional T2-weighted imaging using the dark blood method for detecting
      pulmonary embolisms: comparison with computed tomography angiography.
AB  - PURPOSE: The aim of this study was to assess the potential diagnostic value of
      three-dimensional T2-weighted imaging using the dark blood method for detecting
      pulmonary embolism (PE). MATERIALS AND METHODS: Ten consecutive patients with
      already diagnosed acute PE (five men, five women; mean age 58.6 years, range 35
      79 years) were prospectively enrolled in this study. All patients underwent lung
      magnetic resonance imaging (MRI) with a 1.5-T scanner. MRI was performed on the
      same day as CT angiography (CTA), which was undertaken to monitor treatment. Two
      radiologists performed a consensus evaluation of MRI followed by CTA on a per
      vessel basis: the main pulmonary artery (PA), lobar PA, segmental PA, and
      subsegmental PA. Each modality was evaluated independently on separate days (at
      least 8 weeks apart). The accuracy of MRI for detecting PE was determined by
      comparing it with CTA results, which were used as a reference standard. Cohen's
      kappa analysis was used for statistical analyses. RESULTS: Among the 10 patients,
      pulmonary emboli were seen in 6 of 20 main arteries, 22 of 60 lobar arteries, 35
      of 180 segmental arteries, and 8 of 410 subsegmental arteries on CTA. The
      sensitivities/specificities of MRI were 100%/100% for the main PA, 90.9%/97.3%
      for the lobar PA, and 74.2%/97.9% for the segmental PA, respectively. Altogether,
      304 (83%) of 410 subsegmental arteries were not visualized on MRI and only 1 of
      the 8 emboli in the subsegmental branches was depicted. The kappa values for the
      main, lobar, and segmental arteries were 1.0, 0.89, and 0.77, respectively.
      CONCLUSION: Three-dimensional T2-weighted imaging using the dark blood method
      appears to be principally useful for diagnosing main, lobar, and segmental PEs.

PMID- 21956376
TI  - Psychometric performance of a generic walking scale (Walk-12G) in multiple
      sclerosis and Parkinson's disease.
AB  - Walking difficulties are common in neurological and other disorders, as well as
      among the elderly. There is a need for reliable and valid instruments for
      measuring walking difficulties in everyday life since existing gait tests are
      clinician rated and focus on situation specific capacity. The Walk-12G was
      adapted from the 12-item multiple sclerosis walking scale as a generic patient
      reported rating scale for walking difficulties in everyday life. The aim of this
      study is to examine the psychometric properties of the Walk-12G in people with
      multiple sclerosis (MS) and Parkinson's disease (PD). The Walk-12G was translated
      into Swedish and evaluated qualitatively among 25 people with and without various
      neurological and other conditions. Postal survey (MS, n = 199; PD, n = 189) and
      clinical (PD, n = 36) data were used to test its psychometric properties.
      Respondents considered the Walk-12G relevant and easy to use. Mean completion
      time was 3.5 min. Data completeness was good (<5% missing item responses) and
      tests of scaling assumptions supported summing item scores to a total score
      (corrected item-total correlations >0.6). Coefficient alpha and test-retest
      reliabilities were >0.9, and standard errors of measurement were 2.3-2.8.
      Construct validity was supported by correlations in accordance with a priori
      expectations. Results are similar to those with previous Walk-12G versions,
      indicating that scale adaptation was successful. Data suggest that the Walk-12G
      meets rating scale criteria for clinical trials, making it a valuable complement
      to available gait tests. Further studies involving other samples and application
      of modern psychometric methods are warranted to examine the scale in more detail.

PMID- 21956377
TI  - Executive functions are impaired in heterozygote patients with oculopharyngeal
      muscular dystrophy.
AB  - Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant disorder
      caused by a small expansion of a short polyalanine tract in poly(A) binding
      protein nuclear 1 (PABPN1). It presents with adult onset of progressive eyelid
      drooping, swallowing difficulties and proximal limb weakness, usually without
      involvement of central nervous system (CNS). However, cognitive decline with
      relevant behavioural and psychological symptoms has been recently described in
      homozygous patients. In this study, we performed for the first time an extensive
      neuropsychological and neuropsychiatric evaluation on 11 OPMD heterozygote
      patients. We found that they were less efficient than a matched control sample on
      several tests, particularly those tapping executive functions. Moreover, the
      presence of negative correlation between GCN expansion size and some
      neuropsychological scores raises the issue that CNS involvement might be linked
      to the genetic defect, being worse in patients with larger expansion. Our results
      might be consistent with the toxic gain-of-function theory in the pathogenesis of
      OPMD and hint at a possible direct role of PABPN1 in the CNS also in heterozygote
      patients.

PMID- 21956378
TI  - Mystical experiences occasioned by the hallucinogen psilocybin lead to increases
      in the personality domain of openness.
AB  - A large body of evidence, including longitudinal analyses of personality change,
      suggests that core personality traits are predominantly stable after age 30. To
      our knowledge, no study has demonstrated changes in personality in healthy adults
      after an experimentally manipulated discrete event. Intriguingly, double-blind
      controlled studies have shown that the classic hallucinogen psilocybin occasions
      personally and spiritually significant mystical experiences that predict long
      term changes in behaviors, attitudes and values. In the present report we
      assessed the effect of psilocybin on changes in the five broad domains of
      personality - Neuroticism, Extroversion, Openness, Agreeableness, and
      Conscientiousness. Consistent with participant claims of hallucinogen-occasioned
      increases in aesthetic appreciation, imagination, and creativity, we found
      significant increases in Openness following a high-dose psilocybin session. In
      participants who had mystical experiences during their psilocybin session,
      Openness remained significantly higher than baseline more than 1 year after the
      session. The findings suggest a specific role for psilocybin and mystical-type
      experiences in adult personality change.

PMID- 21956379
TI  - Spinal cord regeneration in a tail autotomizing urodele.
AB  - Adult urodele amphibians possess extensive regenerative abilities, including
      lens, jaws, limbs, and tails. In this study, we examined the cellular events and
      time course of spinal cord regeneration in a species, Plethodon cinereus, that
      has the ability to autotomize its tail as an antipredator strategy. We propose
      that this species may have enhanced regenerative abilities as further
      coadaptations with this antipredator strategy. We examined the expression of
      nestin, vimentin, and glial fibrillary acidic protein (GFAP) after autotomy as
      markers of neural precursor cells and astroglia; we also traced the appearance of
      new neurons using 5-bromo-2'-deoxyuridine/neuronal nuclei (BrdU/NeuN) double
      labeling. As expected, the regenerating ependymal tube was a major source of new
      neurons; however, the spinal cord cranial to the plane of autotomy showed
      significant mitotic activity, more extensive than what is reported for other
      urodeles that cannot autotomize their tails. In addition, this species shows
      upregulation of nestin, vimentin, and GFAP within days after tail autotomy;
      further, this expression is upregulated within the spinal cord cranial to the
      plane of autotomy, not just within the extending ependymal tube, as reported in
      other urodeles. We suggest that enhanced survival of the spinal cord cranial to
      autotomy allows this portion to participate in the enhanced recovery and
      regeneration of the spinal cord.

PMID- 21956380
TI  - Luminescence switching behavior through redox reaction in Ce3+ co-doped
      LaPO4:Tb3+ nanorods: re-dispersible and polymer film.
AB  - Re-dispersible Tb(3+) doped LaPO(4) nanorods have been prepared using ethylene
      glycol (EG) as a capping agent as well as reaction medium at a relatively low
      temperature of 150  degrees C. The X-ray diffraction study reveals that all the
      doped samples are well crystalline with a monoclinic structure of the LaPO(4)
      phase. The luminescence intensity of (5)D(4)->(7)F(5) transition at 543 nm
      (green) is more prominent than that of (5)D(4)->(7)F(6) transition at 487 nm
      (blue) for all the samples. This is related to the polarizing effect from
      [PO(4)](3-) to the Tb(3+) site. Concentration dependent luminescence study shows
      that the luminescence intensity of Tb(3+) increases up to 10 at.% and decreases
      above this. This is due to the concentration quenching effect arising from cross
      relaxation among Tb(3+)-Tb(3+) ions. The results show that nanoparticles prepared
      in EG medium gives an enhanced luminescence compared to that prepared in water.
      This is attributed to the multiphonon relaxation effect from O-H groups
      surrounding over nanoparticles as well as the extent of increase of agglomeration
      among particles for samples prepared in water. Significant enhancement in the
      emission of Tb(3+) is also observed when Ce(3+) is used as the sensitizer in
      LaPO(4):Tb(3+)nanorods. The optimum concentration of Ce(3+) for maximum
      luminescence is found to be 7 at.% in Ce(3+) sensitized LaPO(4):Tb(3+) (5 at.%).
      Based on the energy transfer process from Ce(3+) to Tb(3+), the luminescence of
      Tb(3+) can be switched OFF and ON by performing oxidation and reduction of
      Ce(3+)<->Ce(4+) using KMnO(4) and ascorbic acid, respectively. The samples are re
      dispersible in water, methanol and can be incorporated into polyvinyl alcohol
      (PVA) films. They show a dark green emission under ultraviolet radiation.

PMID- 21956381
TI  - Effects of concurrent arithmetical and syntactic complexity on self-paced
      reaction times and eye fixations.
AB  - Two dual-task experiments (replications of Experiments 1 and 2 in Fedorenko,
      Gibson, & Rohde, Journal of Memory and Language, 56, 246-269 2007) were conducted
      to determine whether syntactic and arithmetical operations share working memory
      resources. Subjects read object- or subject-extracted relative clause sentences
      phrase by phrase in a self-paced task while simultaneously adding or subtracting
      numbers. Experiment 2 measured eye fixations as well as self-paced reaction
      times. In both experiments, there were main effects of syntax and of mathematical
      operation on self-paced reading times, but no interaction of the two. In the
      Experiment 2 eye-tracking results, there were main effects of syntax on first
      pass reading time and total reading time and an interaction between syntax and
      math in total reading time on the noun phrase within the relative clause. The
      findings point to differences in the ways individuals process sentences under
      these dual-task conditions, as compared with viewing sentences during "normal"
      reading conditions, and do not support the view that arithmetical and syntactic
      integration operations share a working memory system.

PMID- 21956382
TI  - Haptic experiences influence visually acquired memories: reference frames during
      multimodal spatial learning.
AB  - In two experiments, we investigated whether reference frames acquired through
      touch could influence memories for locations learned through vision. Participants
      learned two objects through touch, and haptic egocentric (Experiment 1) and
      environmental (Experiment 2) cues encouraged selection of a specific reference
      frame. Participants later learned eight new objects through vision. Haptic cues
      were manipulated, whereas visual learning was held constant in order to observe
      any potential influence of the haptically experienced reference frame on memories
      for visually learned locations. When the haptically experienced reference frame
      was defined primarily by egocentric cues, cue manipulation had no effect on
      memories for objects learned through vision. Instead, visually learned locations
      were remembered using a reference frame selected from the visual study
      perspective. When the haptically experienced reference frame was defined by both
      egocentric and environmental cues, visually learned objects were remembered in
      the context of the haptically experienced reference frame. These findings support
      the common reference frame hypothesis, which proposes that locations learned
      through different sensory modalities are represented within a common reference
      frame.

PMID- 21956385
TI  - Preservation for science: the ecological society of america  and the campaign for
      glacier bay national monument.
AB  - Between 1917 and 1945, the Ecological Society of America (ESA) housed a Committee
      for the Preservation of Natural Conditions specifically charged with identifying
      and taking political action toward the preservation of wilderness sites for
      scientific study. While several historians have analyzed the social and political
      contexts of the Preservation Committee, none has addressed the scientific context
      that gave rise to the Committee and to political activism by ESA members. Among
      the Preservation Committee's lobbying efforts, the naming of Glacier Bay, Alaska,
      as a national monument in 1925 stands out as a unique success. I argue that the
      campaign for the preservation of Glacier Bay reveals the methodological ambitions
      ecologists had for their science in the 1920s and 1930s and demonstrates how
      ecologists understood the role of place in biological field studies. It
      represented preservation for science. Most of the political activities undertaken
      by the ESA in the interwar years, however, turned out to be science for
      conservation, which rarely involved lobbying for the protection of active
      research sites. In conjunction with changes in ecological methodology in the
      1940s, the Committee's unclear scientific mission contributed to its being
      disbanded in 1945.

PMID- 21956383
TI  - DNA-coated microbubbles with biochemically tunable ultrasound contrast activity.

PMID- 21956384
TI  - How facial lesions impact attractiveness and perception: differential effects of
      size and location.
AB  - OBJECTIVES/HYPOTHESIS: To determine the effect of facial lesion size and location
      on perceptions of attractiveness and importance for repair. We hypothesized that
      attractiveness scores and importance for repair would be dependent on lesion size
      and location. STUDY DESIGN: Randomized controlled experiment. METHODS: Forty-five
      subjects viewed 35 photographs of normal faces and faces with lesions of
      different sizes and locations. They rated attractiveness, how disfiguring, how
      bothered, and how important they considered repair. RESULTS: Iterated factor
      analysis showed "bothered, disfigured, and important to repair" addressed the
      same domain, so a disfigured/bothersome/repair factor score (DBRFS) was used. A
      mixed-effects regression model for attractiveness showed small-central and small
      peripheral coefficients were not significantly different, chi(2) (1) = 0.03, P =
      1.000; but large-central and large-peripheral differences and small-central and
      large-peripheral differences were significantly different, chi(2) (1) = 10.34, P
      = 0.004; and chi(2) (1) = 50.55, P < .001, respectively. DBRFS and attractiveness
      were poorly correlated (chi = -0.29). A mixed-effects regression for DBRFS showed
      small-central to large-central and the small-central to large-peripheral
      coefficients were significantly different, chi(2) (1) = 129.20, P < .001; and
      chi(2) (1) = 115.25, P < .001; but large-central to large-peripheral coefficients
      were not, chi(2) (1) = 0.14, P = 1.000. CONCLUSIONS: The attractiveness penalty
      caused by a lesion was correlated with size but not location. Importance to
      repair was correlated with how disturbing and bothersome it was but not with how
      the lesion diminished attractiveness. All large lesions and small central lesions
      were considered important to repair by observers. These results will help us
      predict the true impact of lesions and support evidence-based treatment plans.

PMID- 21956386
TI  - Capture and release.

PMID- 21956387
TI  - Whole-genome sequencing data offer insights into human demography.

PMID- 21956388
TI  - Germline BAP1 mutations and tumor susceptibility.

PMID- 21956389
TI  - GATA2 mutations lead to MDS and AML.

PMID- 21956398
TI  - Optimization of the antioxidant activity of hydroxy-substituted 4-thiaflavanes: a
      proof-of-concept study.
AB  - The design and the synthesis of a new family of hydroxy-4-thiaflavanes, in which
      the reactive phenolic OH is ortho to the sulfur atom of the benzofused oxathiin
      ring, allowed to prepare antioxidants that show rate constants for the reaction
      with peroxyl radicals (k(inh)), and bond dissociation energies (BDE), of the ArO
      H group identical to those of alpha-tocopherol, the main component of vitamin E
      and the most effective lipophilic antioxidant known in nature. The peculiar
      conformation of the six-membered heterocyclic ring prevents the formation of an
      intramolecular hydrogen bond between the OH group and the S atom, while ensuring
      a good stabilization by electron donation of the phenoxyl radical formed after
      the reaction with peroxyl radicals. The preparation of these compounds was
      achieved through an inverse electron demand hetero Diels-Alder reaction of
      styrenes with o-thioquinones, in turn prepared from accurately designed 1,3
      dihydroxy arenes. Properly arranging the substitution pattern on the aromatic
      ring, as in derivatives 9 and 11, allowed to reach values of k(inh) up to
      4.0*10(6) M(-1) s(-1) and BDE((OH)) of 77.2 kcal mol(-1). This approach
      represents an innovative way to obtain highly active antioxidants without using
      strongly electron donating alkylamino groups which are associated with adverse
      toxicological profiles.

PMID- 21956399
TI  - Paroxysmal limb dyskinesia induced by weight: an unusual case of cortical reflex
      seizures.

PMID- 21956400
TI  - Cyclophilin A-EMMPRIN interaction induces invasion of head and neck squamous cell
      carcinoma.
AB  - Extracellular matrix remodeling crucial to tumorigenesis involves proteolytic
      enzymes, primarily matrix metalloproteinases (MMPs). MMP production is stimulated
      by multiple factors, including the extracellular matrix metallo-proteinase
      inducer EMMPRIN/CD147. Overexpression of EMMPRIN, a member of the immunoglobulin
      superfamily, promotes invasion, metastasis, growth and survival of malignant
      cells. Cyclophilin A (CypA) is a multifunctional protein that promotes cancer
      progression in various cancer types. CypA can interact with and activate EMMPRIN;
      however, the role of CypA-EMMPRIN interaction in oncogenicity is not completely
      understood. To investigate tumorigenicity induced by the CypA-EMMPRIN
      interaction, we stimulated EMMPRIN-expressing head and neck squamous cell
      carcinoma (HNSCC) cells with CypA. The 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide dye assay revealed that HNSCC cell proliferation
      increased upon stimulation of the cells with CypA, whereas cisplatin-induced cell
      death decreased after stimulation. Gelatin zymography showed that CypA also
      induced MMP-9 up-regulation. Moreover, HNSCC cell invasion through MatrigelTM
      coated membranes was increased upon stimulation of cells with CypA. This elevated
      invasive potential was abrogated by an EMMPRIN function-blocking antibody. These
      findings suggest that CypA, through its interaction with EMMPRIN, contributes to
      HNSCC tumorigenesis.

PMID- 21956401
TI  - Regionalization in neonatal congenital heart surgery: the impact of distance on
      outcome after discharge.
AB  - Studies have shown improved perioperative outcomes after neonatal heart surgery
      at centers with greater surgical volumes. The impact of increasing distance from
      such centers on outcome after discharge has not yet been reported. Chart review
      and cross-sectional survey were performed on children discharged or transferred
      after undergoing neonatal congenital heart surgery as neonates (<30 days of age)
      from January 2005 to June 2006. The association of distance from center with
      mortality and adverse events was analyzed by univariate and multivariate
      regression and stratified by the Risk Adjustment for Congenital Heart Surgery-1
      for complexity. Among 217 patients, those living further from the surgical center
      were smaller and older at surgery and more likely to be RACHS-1 class 6. Overall
      mortality was 8% (16 of 202) and was not associated with distance. Surveys were
      completed by 109 (54%) families with mean follow-up of 24 (+/- 3) months.
      Unplanned admissions after discharge and unplanned interventions occurred in 45%
      and 40% of patients, respectively. After adjusting for case complexity, living 90
      300 min away from the surgical center was associated with fewer unplanned
      admissions compared with those living <90 min away. After neonatal cardiac
      surgery, adverse events were common. Distance from the surgical center was not
      associated with mortality, but it was associated with morbidity in a nonlinear
      fashion. This relation, its mediators, and its possible impact on mortality and
      later outcomes warrant further study to aid in planning appropriate patient
      follow-up.

PMID- 21956402
TI  - Validation of the MD Anderson Prognostic Risk Model for patients with
      myelodysplastic syndrome.
AB  - BACKGROUND: The proposed MD Anderson Risk Model Score (MDAS) for myelodysplastic
      syndromes (MDS) refines outcome discrimination compared with the International
      Prognostic Scoring System (IPSS). We applied the MDAS to Moffitt Cancer Center
      (MCC) MDS patients to validate its prognostic utility. METHODS: This was a
      retrospective analysis of MDS cases, as defined by World Health Organization
      criteria, from the Moffitt database, with confirmatory chart review. RESULTS: A
      total of 775 patients evaluated between January 2001 and December 2009 were
      included. Patients were reclassified by MDAS as low (20.6%), intermediate-1
      (31%), intermediate-2 (21%), high risk (16.1%), and unknown (11.2%). Median
      overall survival (OS) from diagnosis was 92, 49, 27, and 14 months for low,
      intermediate-1, intermediate-2, and high-risk MDAS groups, respectively (P <
      .005). Median OS from referral was 61, 28, 15, and 8 months (P < .005),
      respectively. Among 484 patients classified by IPSS as low or intermediate-1
      risk, 25% were up-staged as intermediate-2 or high risk by MDAS; 4 prognostically
      distinct subgroups were identified among lower risk IPSS categories with median
      OS of 93, 53, 31, and 18 months (P < .005). Among 201 intermediate-2 or high-risk
      IPSS patients, 15.4% were down-staged to intermediate-1 by MDAS, with 3 groups
      identified by MDAS having median OS of 33, 23, and 14 months. Acute myeloid
      leukemia transformation rate was highest among high-risk MDAS (50.4%). In Cox
      regression analysis, higher risk MDAS predicted inferior OS (hazard ratio 1.42; P
      < .005) independent of IPSS. CONCLUSIONS: Our data validated MDAS' prognostic
      value. MDAS is complementary to IPSS and refines prognostic precision.

PMID- 21956403
TI  - The effects of iloprost on colonic anastomotic healing in rats.
AB  - PURPOSE: The purpose of this experimental study is to investigate the effects of
      iloprost on colonic anastomotic healing in rats, after intraperitoneal
      administration. METHODS: Forty male Albino-Wistar rats were randomized into two
      groups of twenty animals each. They all underwent colonic resection followed by
      an inverted anastomosis. The rats of Group A (control) received 3 ml of NaCl
      intraperitoneally, while those of Group B (iloprost) received iloprost (2 MUg/kg
      body weight), immediately postoperatively and daily until killed. Each group was
      further divided into two equal subgroups, depending on the day of killing. The
      animals of subgroups 1 were killed on the fourth postoperative day, while those
      of subgroups 2 on the eighth. Macroscopical and histological assessments were
      performed. Besides, anastomotic bursting pressures and the tissue concentrations
      in hydroxyproline and collagenase I were also evaluated. RESULTS: No anastomotic
      dehiscence was noted. The mean bursting pressure was higher in the iloprost group
      compared with the control group, but a significant difference was revealed only
      on the fourth postoperative day. Furthermore, iloprost significantly increased
      the new vessel formation on the fourth, as well as on the eighth postoperative
      day. CONCLUSION: Iloprost enhances the early phase of colonic anastomotic healing
      in rats.

PMID- 21956404
TI  - Integration of diffusion-weighted MRI data and a simple mathematical model to
      predict breast tumor cellularity during neoadjuvant chemotherapy.
AB  - Diffusion-weighted magnetic resonance imaging data obtained early in the course
      of therapy can be used to estimate tumor proliferation rates, and the estimated
      rates can be used to predict tumor cellularity at the conclusion of therapy. Six
      patients underwent diffusion-weighted magnetic resonance imaging immediately
      before, after one cycle, and after all cycles of neoadjuvant chemotherapy.
      Apparent diffusion coefficient values were calculated for each voxel and for a
      whole tumor region of interest. Proliferation rates were estimated using the
      apparent diffusion coefficient data from the first two time points and then used
      with the logistic model of tumor growth to predict cellularity after therapy. The
      predicted number of tumor cells was then correlated to the corresponding
      experimental data. Pearson's correlation coefficient for the region of interest
      analysis yielded 0.95 (P = 0.004), and, after applying a 3 * 3 mean filter to the
      apparent diffusion coefficient data, the voxel-by-voxel analysis yielded a
      Pearson correlation coefficient of 0.70 +/- 0.10 (P < 0.05).

PMID- 21956405
TI  - Clusters of acute respiratory illness associated with human enterovirus 68--Asia,
      Europe, and United States, 2008-2010.
AB  - In the past 2 years, CDC has learned of several clusters of respiratory illness
      associated with human enterovirus 68 (HEV68), including severe disease. HEV68 is
      a unique enterovirus that shares epidemiologic and biologic features with human
      rhinoviruses (HRV). First isolated in California in 1962 from four children with
      bronchiolitis and pneumonia, HEV68 has been reported rarely since that time and
      the full spectrum of illness that it can cause is unknown. The six clusters of
      respiratory illness associated with HEV68 described in this report occurred in
      Asia, Europe, and the United States during 2008-2010. HEV68 infection was
      associated with respiratory illness ranging from relatively mild illness that did
      not require hospitalization to severe illness requiring intensive care and
      mechanical ventilation. Three cases, two in the Philippines and one in Japan,
      were fatal. In these six clusters, HEV68 disproportionately occurred among
      children. CDC learned of clusters of HEV68 from public health agencies requesting
      consultation or diagnostic assistance and from reports presented at scientific
      conferences. In each cluster, HEV68 was diagnosed by reverse transcription
      polymerase chain reaction (RT-PCR) testing targeting the 5'-nontranslated region,
      followed by partial sequencing of the structural protein genes, VP4-VP2, VP1, or
      both, to give definitive, enterovirus type-specific information. This report
      highlights HEV68 as an increasingly recognized cause of respiratory illness.
      Clinicians should be aware of HEV68 as one of many causes of viral respiratory
      disease and should report clusters of unexplained respiratory illness to the
      appropriate public health agency.

PMID- 21956406
TI  - Current cigarette smoking prevalence among working adults--United States, 2004
      2010.
AB  - Cigarette smoking is among the most important modifiable risk factors for adverse
      health outcomes and a major cause of morbidity and mortality. Current cigarette
      smoking prevalence among all adults aged >=18 years has decreased 42.4% since
      1965, but declines in current smoking prevalence have slowed during the past 5
      years (declining from 20.9% in 2005 to 19.3% in 2010) and did not meet the
      Healthy People 2010 (HP2010) objective to reduce cigarette smoking among adults
      to <=12%. Targeted workplace tobacco control interventions have been effective in
      reducing smoking prevalence and exposure to secondhand smoke; therefore, CDC
      analyzed National Health Interview Survey (NHIS) data for 2004-2010 to describe
      current cigarette smoking prevalence among currently working U.S. adults by
      industry and occupation. This report describes the results of that analysis,
      which found that, overall, age-adjusted cigarette smoking prevalence among
      working adults was 19.6% and was highest among those with less than a high school
      education (28.4%), those with no health insurance (28.6%), those living below the
      federal poverty level (27.7%), and those aged 18-24 years (23.8%). Substantial
      differences in smoking prevalence were observed across industry and occupation
      groups. By industry, age-adjusted cigarette smoking prevalence among working
      adults ranged from 9.7% in education services to 30.0% in mining; by occupation
      group, prevalence ranged from 8.7% in education, training, and library to 31.4%
      in construction and extraction. Although some progress has been made in reducing
      smoking prevalence among working adults, additional effective employer
      interventions need to be implemented, including health insurance coverage for
      cessation treatments, easily accessible help for those who want to quit, and
      smoke-free workplace policies.

PMID- 21956407
TI  - Severe illness from 2009 pandemic influenza A (H1N1)--Utah, 2009-10 influenza
      season.
AB  - Influenza-associated hospitalizations have been a reportable condition in Utah
      since 2005, and surveillance for influenza hospitalizations has been a valuable
      tool for identifying and tracking the population impact of serious influenza
      illness. During the 2009 influenza A (H1N1) pandemic, Utah public health
      officials used comparisons with hospitalization data from three previous
      influenza seasons to rapidly assess the impact of 2009 H1N1 and enable public
      health authorities to target persons at greatest risk for severe illness. This
      report summarizes the results of that assessment, which determined that 1,327
      2009 H1N1 hospitalizations were reported, compared with an average of 435
      seasonal influenza hospitalizations during three previous influenza seasons, and
      25.5% of 2009 H1N1 hospitalizations resulted in severe illness (intensive-care
      unit [ICU] admission or death), compared with 14.0% of seasonal influenza
      hospitalizations. In addition, 2009 H1N1 disproportionately affected
      racial/ethnic minorities, pregnant women, and residents of Salt Lake County (the
      state's most densely populated county). During the 4-month "spring wave" of the
      H1N1 pandemic, a greater percentage of hospitalizations (30.9%) resulted in
      severe illness than during the 9-month "fall wave" (23.0%). Surveillance for
      influenza hospitalizations can provide essential data to public health
      authorities that will help them identify those populations at greatest risk for
      severe illness.

PMID- 21956408
TI  - Progress in implementing measles mortality reduction strategies--India, 2010
      2011.
AB  - In 2005, an estimated 92,000 deaths occurred in India from measles among children
      aged <5 years. Estimates from 2008 indicate that 77% of global measles mortality
      was attributable to measles deaths in the World Health Organization (WHO) South
      East Asia Region, the majority of which occurred in India. These figures
      highlight the importance of India in attaining regional and global measles
      mortality reduction targets. In 2008, the Indian National Technical Advisory
      Group on Immunization (NTAGI) recommended introduction of a second dose of
      measles-containing vaccine (MCV2), delivered through routine vaccination in
      states with >=80% coverage with the first dose of measles-containing vaccine
      (MCV1), or through mass vaccination campaigns in states with <80% MCV1 coverage.
      Based on these recommendations, the government of India initiated MCV2
      introduction in late 2010. This report provides an update on MCV1 coverage,
      progress in implementing MCV2, and measles outbreak surveillance activities
      conducted in eight states during 2006-2010. India has initiated implementation of
      a measles mortality reduction strategy, but the pace of implementation is
      variable across states. Strong national and state leadership and commitment to
      rapid reduction of measles mortality are essential to achieve the full benefits
      of this strategy.

PMID- 21956410
TI  - Facile xenon capture and release at room temperature using a metal-organic
      framework: a comparison with activated charcoal.
AB  - Two well-known metal-organic frameworks (MOF-5, NiDOBDC) were synthesized and
      studied for facile xenon capture and separation. Our results indicate that
      NiDOBDC adsorbs significantly more xenon than MOF-5, and is more selective for
      xenon over krypton than activated carbon.

PMID- 21956409
TI  - The convergence of cochlear implantation with induced pluripotent stem cell
      therapy.
AB  - According to 2010 estimates from The National Institute on Deafness and other
      Communication Disorders, approximately 17% (36 million) American adults have
      reported some degree of hearing loss. Currently, the only clinical treatment
      available for those with severe-to-profound hearing loss is a cochlear implant,
      which is designed to electrically stimulate the auditory nerve in the absence of
      hair cells. Whilst the cochlear implant has been revolutionary in terms of
      providing hearing to the severe-to-profoundly deaf, there are variations in
      cochlear implant performance which may be related to the degree of degeneration
      of auditory neurons following hearing loss. Hence, numerous experimental studies
      have focused on enhancing the efficacy of cochlear implants by using
      neurotrophins to preserve the auditory neurons, and more recently, attempting to
      replace these dying cells with new neurons derived from stem cells. As a result,
      several groups are now investigating the potential for both embryonic and adult
      stem cells to replace the degenerating sensory elements in the deaf cochlea.
      Recent advances in our knowledge of stem cells and the development of induced
      pluripotency by Takahashi and Yamanaka in 2006, have opened a new realm of
      science focused on the use of induced pluripotent stem (iPS) cells for
      therapeutic purposes. This review will provide a broad overview of the potential
      benefits and challenges of using iPS cells in combination with a cochlear implant
      for the treatment of hearing loss, including differentiation of iPS cells into an
      auditory neural lineage and clinically relevant transplantation approaches.

PMID- 21956411
TI  - Clinical review: Ethical and medical considerations of androgen deprivation
      treatment of sex offenders.
AB  - CONTEXT: Blood testosterone codetermines the threshold for erotosexual imagery
      and sexual activity. Androgen deprivation may therefore have a place in the
      treatment of unacceptable sexual behavior. Although androgen deprivation can be
      effective for sex offenders, their basic human rights must be respected;
      otherwise such treatment constitutes a violation of their physical integrity and
      is ethically unacceptable. As experience in treating prostate cancers
      demonstrates, androgen deprivation may have serious side effects.
      Endocrinologists are qualified to advise on and monitor androgen deprivation, but
      they are placed in an atypical position because the indication for such treatment
      is not dictated by endocrine disease. OBJECTIVE: The aim of this study was to
      provide an ethical framework for advising on androgen deprivation treatment of
      sex offenders and dealing with side effects. EVIDENCE ACQUISITION AND SYNTHESIS:
      A literature search was conducted in PubMed, Psychinfo, and references from the
      multiple systematic reviews and meta-analyses published on this topic. An attempt
      has been made to provide an appreciation of the ethical aspects of androgen
      deprivation in sex offenders, the efficacy of treatment, the potential risks of
      treatment, therapeutic options, and recommendations for monitoring treatment.
      CONCLUSIONS: Provided that the human rights of sex offenders are respected and
      informed consent is given, androgen deprivation within a comprehensive framework
      of psychotherapeutic treatment can make a meaningful contribution to the
      prevention of recidivism by enabling better control of sexual impulses. Knowledge
      of side effects and their treatment has been mostly gleaned from experience with
      prostate cancer patients, and this should be made available to sex offenders
      undergoing androgen deprivation.

PMID- 21956412
TI  - Morphological mosaicism of the pancreatic islets: a novel anatomopathological
      form of persistent hyperinsulinemic hypoglycemia of infancy.
AB  - BACKGROUND: Morphological studies of the pancreas in persistent hyperinsulinemic
      hypoglycemia of infancy (PHHI) have focused on the diagnosis of focal vs. diffuse
      forms, a distinction that determines the optimal surgical management. ABCC8 or
      KCNJ11 genomic mutations are present in most of them. AIM: Our aim was to report
      a new form of PHHI with peculiar morphological and clinical characteristics.
      RESEARCH DESIGN AND METHODS: Histopathological review of 217 pancreatic PHHI
      specimens revealed 16 cases morphologically different from diffuse and focal
      forms. They were analyzed by conventional microscopy, quantitative morphometry,
      immunohistochemistry, and in situ hybridization. RESULTS: Their morphological
      peculiarity was the coexistence of two types of islet: large islets with
      cytoplasm-rich beta-cells and occasional enlarged nuclei and shrunken islets with
      beta-cells exhibiting little cytoplasm and small nuclei. In small islets, beta
      cells had abundant insulin content but limited amount of Golgi proinsulin. Large
      islets had low insulin storage and high proinsulin production and were mostly
      confined to a few lobules. No evidence for K(ATP) channels involvement or 11p15
      deletion was found. Genomic mutations for ABCC8, KCNJ11, and GCK were absent.
      Patients had normal birth weight and late hypoglycemia onset and improved with
      diazoxide. Ten were cured by limited pancreatectomy. Six recurred after surgery
      and were medically controlled. CONCLUSION: This new form of PHHI is characterized
      by a morphological mosaicism. Pathologists should recognize this mosaicism on
      intraoperative frozen sections because it is often curable by partial
      pancreatectomy. The currently unknown genetic background does not involve the
      classical genomic mutations responsible for diffuse and focal PHHI.

PMID- 21956413
TI  - Exogenous insulin enhances glucose-stimulated insulin response in healthy humans
      independent of changes in free fatty acids.
AB  - CONTEXT: Islet beta-cells express both insulin receptors and insulin signaling
      proteins. Recent studies suggest insulin signaling is physiologically important
      for glucose sensing. OBJECTIVE: Preexposure to insulin enhances glucose
      stimulated insulin secretion (GSIS) in healthy humans. We evaluated whether the
      effect of insulin to potentiate GSIS is modulated through regulation of free
      fatty acids (FFA). DESIGN AND SETTING: Subjects were studied on three occasions
      in this single-site study at an academic institution clinical research center.
      PATIENTS: Subjects included nine healthy volunteers. INTERVENTIONS: Glucose
      induced insulin response was assessed on three occasions after 4 h saline (low
      insulin/sham) or isoglycemic-hyperinsulinemic (high insulin) clamps with or
      without intralipid and heparin infusion, using B28 Asp-insulin that could be
      distinguished from endogenous insulin immunologically. During the last 80 min of
      all three clamps, additional glucose was administered to stimulate insulin
      secretion (GSIS) with glucose concentrations maintained at similar concentrations
      during all studies. MAIN OUTCOME MEASURE: beta-Cell response to glucose
      stimulation was assessed. RESULTS: Preexposure to exogenous insulin increased the
      endogenous insulin-secretory response to glucose by 32% compared with sham clamp
      (P = 0.001). This was accompanied by a drop in FFA during hyperinsulinemic clamp
      compared with the sham clamp (0.06 +/- 0.02 vs. 0.60 +/- 0.09 mEq/liter,
      respectively), which was prevented during the hyperinsulinemic clamp with
      intralipid/heparin infusion (1.27 +/- 0.17 mEq/liter). After preexposure to
      insulin with intralipid/heparin infusion to maintain FFA concentration, GSIS was
      21% higher compared with sham clamp (P < 0.04) and similar to preexposure to
      insulin without intralipid/heparin (P = 0.2). CONCLUSIONS: Insulin potentiates
      glucose-stimulated insulin response independent of FFA concentrations in healthy
      humans.

PMID- 21956415
TI  - Cardiovascular disease and risk factors in PCOS women of postmenopausal age: a 21
      year controlled follow-up study.
AB  - CONTEXT: Polycystic ovary syndrome (PCOS) is associated with the metabolic
      syndrome and, consequently, with a potentially increased risk of cardiovascular
      disease (CVD) and related mortality later in life. Studies regarding CVD and
      mortality in PCOS women well into the postmenopausal age are lacking. OBJECTIVE:
      Our objective was to examine whether postmenopausal PCOS women differ from
      controls regarding cardiovascular risk factors, myocardial infarction (MI),
      stroke and mortality. DESIGN AND SETTING: We conducted, at a university hospital,
      a prospective study of 35 PCOS women (61-79 yr) and 120 age-matched controls. The
      study was performed 21 yr after the initial study. PARTICIPANTS: Twenty-five PCOS
      women (Rotterdam criteria) and 68 controls participated in all examinations. Data
      on morbidity were based on 32 of 34 PCOS women and on 95 of 119 controls.
      INTERVENTIONS: INTERVENTIONS included reexamination, interviews, and data from
      the National Board of Health and Welfare and from the Hospital Discharge
      Registry. MAIN OUTCOME MEASURES: Blood pressure, glucose, insulin, triglycerides,
      total cholesterol, high- and low-density lipoprotein, apolipoprotein A1 and B,
      fibrinogen, and plasminogen activator inhibitor antigen were studied. Incidences
      of MI, stroke, hypertension, diabetes, cancer, cause of death, and age at death
      were recorded. RESULTS: PCOS women had a higher prevalence of hypertension (P =
      0.008) and higher triglyceride levels (P = 0.012) than controls. MI, stroke,
      diabetes, cancer, and mortality prevalence was similar in the two cohorts with
      similar body mass index. CONCLUSIONS: The well-described cardiovascular/metabolic
      risk profile in pre- and perimenopausal PCOS women does not entail an evident
      increase in cardiovascular events during the postmenopausal period.

PMID- 21956414
TI  - Incidence and clinical characteristics of thyroid cancer in prospective series of
      individuals with Cowden and Cowden-like syndrome characterized by germline PTEN,
      SDH, or KLLN alterations.
AB  - CONTEXT: Thyroid cancer is believed to be an important component of Cowden
      syndrome (CS). Germline PTEN and SDHx mutations and KLLN epimutation cause CS and
      CS-like phenotypes. Despite the established association, little is known about
      the incidence and clinical features of thyroid cancer found in CS/CS-like
      patients. OBJECTIVE: The aim of the study was to compare incidence, clinical, and
      histological characteristics of epithelial thyroid cancers in CS/CS-like
      individuals, in the context of PTEN, SDHx, and KLLN status. DESIGN AND
      PARTICIPANTS: The study encompassed a 5-yr, multicenter, prospective accrual of
      2723 CS and CS-like patients, all of whom had comprehensive PTEN analysis. SDHx
      mutation analysis occurred in those without PTEN mutations/variations and
      elevated manganese superoxide dismutase (MnSOD) levels. KLLN epimutation analysis
      was performed in the subset without any PTEN or SDHx mutation/deletion/
      variant/polymorphism. MAIN OUTCOME MEASURES: Gene-specific thyroid cancer
      histologies, demographic and clinical information, and adjusted standardized
      incidence rates were studied. RESULTS: Of 2723 CS/CS-like patients, 664 had
      thyroid cancer. Standardized incidence rates for thyroid cancer were 72 [95%
      confidence interval (CI), 51-99; P < 0.001] for pathogenic PTEN mutations, 63
      (95% CI, 42-92; P < 0.001) for SDHx variants, and 45 (95% CI, 26-73; P < 0.001)
      for KLLN epimutations. All six (16.7%) diagnosed under age 18 yr carried
      pathogenic PTEN mutations. Follicular thyroid cancer was overrepresented in PTEN
      mutation-positive cases compared to those with SDHx and KLLN alterations. PTEN
      frameshift mutations were found in 31% of patients with thyroid cancer compared
      to 17% in those without thyroid cancer. CONCLUSIONS: CS/CS-like patients have
      elevated risks of follicular thyroid cancer due to PTEN pathogenic mutations and
      of papillary thyroid cancer from SDHx and KLLN alterations. Children presenting
      with thyroid cancer should be tested for PTEN mutations.

PMID- 21956416
TI  - The roles of IL-6, IL-10, and IL-1RA in obesity and insulin resistance in African
      Americans.
AB  - OBJECTIVE: The aim of the study was to investigate the associations between IL-1
      receptor antagonist (IL-1RA), IL-6, IL-10, measures of obesity, and insulin
      resistance in African-Americans. RESEARCH DESIGN AND METHODS: Nondiabetic
      participants (n = 1025) of the Howard University Family Study were investigated
      for associations between serum IL (IL-1RA, IL-6, IL-10), measures of obesity, and
      insulin resistance, with adjustment for age and sex. Measures of obesity included
      body mass index, waist circumference, hip circumference, waist-to-hip ratio, and
      percent fat mass. Insulin resistance was assessed using the homeostasis model
      assessment of insulin resistance (HOMA-IR). Data were analyzed with R statistical
      software using linear regression and likelihood ratio tests. RESULTS: IL-1RA and
      IL-6 were associated with measures of obesity and insulin resistance, explaining
      4-12.7% of the variance observed (P values < 0.001). IL-1RA was bimodally
      distributed and therefore was analyzed based on grouping those with low vs. high
      IL-1RA levels. High IL-1RA explained up to 20 and 12% of the variance in measures
      of obesity and HOMA-IR, respectively. Among the IL, only high IL-1RA improved the
      fit of models regressing HOMA-IR on measures of obesity. In contrast, all
      measures of obesity improved the fit of models regressing HOMA-IR on IL. IL-10
      was not associated with obesity measures or HOMA-IR. CONCLUSIONS: High IL-1RA
      levels and obesity measures are associated with HOMA-IR in this population-based
      sample of African-Americans. The results suggest that obesity and increased
      levels of IL-1RA both contribute to the development of insulin resistance.

PMID- 21956417
TI  - Relationship between urinary bisphenol A levels and diabetes mellitus.
AB  - BACKGROUND: Bisphenol A (BPA) is a widely used chemical in the manufacture of
      polycarbonate plastics and epoxy resins. Recent animal studies have suggested
      that BPA exposure may have a role in the development of weight gain, insulin
      resistance, pancreatic endocrine dysfunction, thyroid hormone disruption, and
      several other mechanisms involved in the development of diabetes. However, few
      human studies have examined the association between markers of BPA exposure and
      diabetes mellitus. METHODS: We examined the association between urinary BPA
      levels and diabetes mellitus in the National Health and Nutritional Examination
      Survey (NHANES) 2003-2008. Urinary BPA levels were examined in quartiles. The
      main outcome of interest was diabetes mellitus defined according the latest
      American Diabetes Association guidelines. RESULTS: Overall, we observed a
      positive association between increasing levels of urinary BPA and diabetes
      mellitus, independent of confounding factors such as age, gender, race/ethnicity,
      body mass index, and serum cholesterol levels. Compared to quartile 1 (referent),
      the multivariate-adjusted odds ratio (95% confidence interval) of diabetes
      associated with quartile 4 was 1.68 (1.22-2.30) (p-trend = 0.002). The
      association was present among normal-weight as well as overweight and obese
      subjects. CONCLUSIONS: Urinary BPA levels are found to be associated with
      diabetes mellitus independent of traditional diabetes risk factors. Future
      prospective studies are needed to confirm or disprove this finding.

PMID- 21956418
TI  - miR-191 down-regulation plays a role in thyroid follicular tumors through CDK6
      targeting.
AB  - CONTEXT: Well-differentiated thyroid carcinomas include papillary (PTC) and
      follicular (FTC) carcinomas. FTC is usually a more aggressive form of cancer than
      the more common papillary type. miR-191 expression is frequently altered in
      several neoplasias, being up-regulated in some cases, such as pancreatic
      carcinomas, and down-regulated in other carcinomas, such as melanomas. OBJECTIVE:
      The objective was to evaluate the expression and the role of miR-191 in thyroid
      carcinogenesis. DESIGN: The expression of miR-191 was analyzed in tissues from
      patients with follicular adenoma (n = 24), FTC (n = 24), PTC (n = 15), anaplastic
      thyroid carcinoma (n = 8), and the follicular variant of PTC (n = 6) compared
      with normal thyroid tissues by quantitative RT-PCR. miR-191 expression was
      restored in the follicular thyroid cell line WRO, and the effects on cell
      proliferation, migration, and target expression were evaluated. RESULTS: miR-191
      is down-regulated in follicular adenoma, FTC, and follicular variant of PTC. We
      identified CDK6, a serine-threonine kinase involved in the control of cell cycle
      progression, as a novel target of miR-191. Restoration of miR-191 expression in
      WRO cells reduces cell growth and migration rate on vitronectin. CDK6
      overexpression, correlated with miR-191 down-regulation, was found in follicular
      adenoma and FTC, suggesting a role of miR-191 down-regulation in the generation
      of these neoplasias. CONCLUSIONS: Our results suggest that miR-191 down
      regulation plays a role in thyroid neoplasias of the follicular histotype, likely
      by targeting CDK6.

PMID- 21956420
TI  - Innate immune activation and thyroid autoimmunity.
AB  - CONTEXT: Autoimmune thyroid disease (AITD) is the archetypal organ-specific
      autoimmune disorder and is characterized by the production of thyroid
      autoantibodies. However, the underlying mechanisms by which specific antibodies
      against thyroid proteins are produced are largely unknown. EVIDENCE ACQUISITION:
      Published peer-reviewed basic and clinical literatures on immunology and
      autoimmune diseases were identified through searches of PubMed for articles
      published from January 1971 to May 2011. Articles resulting from these searches
      and relevant references cited in those articles were reviewed. All the relevant
      articles were written in English. EVIDENCE SYNTHESIS: Recent studies have
      indicated that innate immune responses induced by both exogenous and endogenous
      factors affect the phenotype and severity of autoimmune reactions. One of the
      recent topics is the effect of self-genomic DNA fragments on immune activation.
      Expression of major histocompatibility complex class II on the autoimmune target
      cells seems to play an important role in the presentation of endogenous antigens.
      Accumulated evidence from animal models has generated new insights into the
      pathogenesis of AITD. CONCLUSION: AITD develops by a combination of genetic
      susceptibility and environmental factors. Innate immune responses are associated
      with thyroid dysfunction, tissue destruction, and the likely development and
      perpetuation of AITD. In addition to the other factors, cell injury may
      contribute to the activation of innate immune response and the development of
      AITD.

PMID- 21956419
TI  - Clinical review: Pituitary carcinoma: difficult diagnosis and treatment.
AB  - CONTEXT: Although pituitary tumors are common, pituitary carcinoma is very rare
      and is only diagnosed when pituitary tumor noncontiguous with the sellar region
      is demonstrated. Diagnosis is difficult, resulting in delays that may adversely
      effect outcome that is traditionally poor. Barriers to earlier diagnosis and
      management strategies for pituitary carcinoma are discussed. EVIDENCE
      ACQUISITION: PubMed was employed to identify relevant studies, a review of the
      literature was conducted, and data were summarized and integrated from the
      author's perspective. EVIDENCE SYNTHESIS: The available data highlight the
      difficulties in diagnosis and management and practical challenges in conducting
      clinical trials in this rare condition. They suggest that earlier diagnosis with
      aggressive multimodal therapy may be advantageous in some cases. CONCLUSIONS:
      Although pituitary carcinoma remains difficult to diagnose and treat, recent
      developments have led to improved outcomes in selected cases. With broader use of
      molecular markers, efforts to modify current histopathological criteria for
      pituitary carcinoma diagnosis may now be possible. This would assist earlier
      diagnosis and, in combination with targeted therapies, potentially improve long
      term survival.

PMID- 21956422
TI  - Clinical review: Cardiovascular consequences of ovarian disruption: a focus on
      functional hypothalamic amenorrhea in physically active women.
AB  - CONTEXT: Evidence indicates that hypoestrogenemia is linked with accelerated
      progression of atherosclerosis. Premenopausal women presenting with ovulatory
      disruption due to functional hypothalamic amenorrhea (FHA) are characterized by
      hypoestrogenemia. One common and reversible form of FHA in association with
      energy deficiency is exercise-associated amenorrhea (EAA). EVIDENCE ACQUISITION:
      Articles were found via PubMed search for both original and review articles based
      on peer review publications between 1974 and 2011 reporting on cardiovascular
      changes in women with FHA, with emphasis placed on women with EAA. EVIDENCE
      SYNTHESIS: Despite participation in regular exercise training, hypoestrogenic
      women with EAA demonstrate paradoxical changes in cardiovascular function,
      including endothelial dysfunction, a known permissive factor for the progression
      and development of atherosclerosis. Such alterations suggest that the beneficial
      effects of regular exercise training on vascular function are obviated in the
      face of hypoestrogenemia. The long-term cardiovascular consequences of altered
      vascular function in response to ovulatory disruption in women with EAA remain to
      be determined. Retrospective data, however, suggest premature development and
      progression of coronary artery disease in older premenopausal women reporting a
      history of hypothalamic ovulatory disruption. Importantly, in women with EAA,
      estrogen therapy, folic acid supplementation without change in menstrual status,
      and resumption of menses restores endothelial function. In this review, we focus
      on the influence of hypoestrogenemia in association with energy deficiency in
      mediating changes in cardiovascular function in women with EAA, including
      endothelial function, regional blood flow, lipid profile, and autonomic control
      of blood pressure, heart rate, and baroreflex sensitivity. The influence of
      exercise training is also considered. CONCLUSION: With the premenopausal years
      typically considered to be cardioprotective in association with normal ovarian
      function, ovarian disruption in women with EAA is of importance. Further
      investigation of the short-term, and potentially long-term, cardiovascular
      consequences of hypoestrogenemia in women with EAA is recommended.

PMID- 21956421
TI  - Fibroblasts expressing the thyrotropin receptor overarch thyroid and orbit in
      Graves' disease.
AB  - CONTEXT: Graves' disease (GD) is a systemic autoimmune syndrome comprising
      manifestations in thyroid and orbital connective tissue. The link between these
      two tissues in GD eludes our understanding. Patients with GD have increased
      frequency of circulating monocyte lineage cells known as fibrocytes. These
      fibrocytes infiltrate orbital connective tissues in thyroid-associated
      ophthalmopathy and express functional TSH receptor (TSHR). OBJECTIVE: The aim of
      the study was to identify and characterize CD34(+) fibrocytes in thyroid tissue.
      DESIGN/SETTING/PARTICIPANTS: Patients undergoing surgical thyroidectomy at two
      academic medical centers were recruited to the study. MAIN OUTCOME MEASURES: We
      performed immunohistochemistry, flow cytometry, real-time PCR, cytokine-specific
      ELISA, and cell differentiation. RESULTS: CD34(+)ColI(+)CXCR4(+)TSHR(+) cells can
      be identified in situ in thyroid tissue from donors with GD, Hashimoto's
      thyroiditis, or in normal-appearing tissue. Thyroid fibroblasts cultivated from
      these glands express a CD34(-)ColI(+)CXCR4(+)TSHR(+) phenotype. TSHR levels are
      higher than those in orbital fibroblasts. When treated with TSH, thyroid
      fibroblasts generate IL-6 and IL-8. The induction of IL-6 can be blocked by
      dexamethasone, a chemical inhibitor of Akt/Pkb, and by knocking down Akt with a
      specific small interfering RNA. When treated with TGF-beta or rosiglitazone,
      thyroid fibroblasts differentiate into myofibrocytes or adipocytes, respectively.
      CONCLUSIONS: ColI(+)CXCR4(+)TSHR(+) thyroid fibroblasts resemble orbital
      fibroblasts and circulating fibrocytes. CD34(+) fibrocytes appear to infiltrate
      both tissues in GD. Thyroid fibroblasts lose CD34 display in culture, unlike
      orbital fibroblasts and circulating fibrocytes. Fibrocytes and their fibroblast
      derivatives may participate in the pathogenesis of thyroid autoimmunity after
      TSHR activation. They could represent a therapeutic target for these diseases.

PMID- 21956423
TI  - Circulating concentrations of monocyte chemoattractant protein-1, plasminogen
      activator inhibitor-1, and soluble leukocyte adhesion molecule-1 in
      overweight/obese men and women consuming fructose- or glucose-sweetened beverages
      for 10 weeks.
AB  - CONTEXT: Results from animal studies suggest that consumption of large amounts of
      fructose can promote inflammation and impair fibrinolysis. Data describing the
      effects of fructose consumption on circulating levels of proinflammatory and
      prothrombotic markers in humans are unavailable. OBJECTIVE: Our objective was to
      determine the effects of 10 wk of dietary fructose or glucose consumption on
      plasma concentrations of monocyte chemoattractant protein-1 (MCP-1), plasminogen
      activator inhibitor-1 (PAI-1), E-selectin, intercellular adhesion molecule-1, C
      reactive protein, and IL-6. DESIGN AND SETTING: This was a parallel-arm study
      with two inpatient phases (2 wk baseline, final 2 wk intervention), conducted in
      a clinical research facility, and an outpatient phase (8 wk) during which
      subjects resided at home. PARTICIPANTS: Participants were older (40-72 yr),
      overweight/obese (body mass index = 25-35 kg/m(2)) men (n = 16) and women (n =
      15). INTERVENTIONS: Participants consumed glucose- or fructose-sweetened
      beverages providing 25% of energy requirements for 10 wk. Blood samples were
      collected at baseline and during the 10th week of intervention. MAIN OUTCOME
      MEASURES: Fasting concentrations of MCP-1 (P = 0.009), PAI-1 (P = 0.002), and E
      selectin (P = 0.048) as well as postprandial concentrations of PAI-1 (P < 0.0001)
      increased in subjects consuming fructose but not in those consuming glucose.
      Fasting levels of C-reactive protein, IL-6, and intercellular adhesion molecule-1
      were not changed in either group. CONCLUSIONS: Consumption of fructose for 10 wk
      leads to increases of MCP-1, PAI-1, and E-selectin. These findings suggest the
      possibility that fructose may contribute to the development of the metabolic
      syndrome via effects on proinflammatory and prothrombotic mediators.

PMID- 21956424
TI  - Association of glucocorticoid use and low 25-hydroxyvitamin D levels: results
      from the National Health and Nutrition Examination Survey (NHANES): 2001-2006.
AB  - CONTEXT: In many disorders requiring steroid therapy, there is substantial
      decrease in bone mineral density. The association between steroid use and 25
      hydroxyvitamin D [25(OH)D] deficiency has not been confirmed in large population
      based studies, and currently there are no specific vitamin D recommendations for
      steroid users. OBJECTIVE: The aim of the study was to evaluate the association of
      serum 25(OH)D deficiency [defined as 25(OH)D <10 ng/ml] with oral steroid use.
      DESIGN: Cross-sectional analysis was performed using NHANES 2001-2006. SETTING:
      We analyzed a nationally representative sample of U.S. children and adults.
      PARTICIPANTS: The study sample consisted of children, adolescents, and adults
      from NHANES 2001-2006 (n = 22,650), representative of 286 million U.S. residents,
      with serum 25(OH)D levels and data on other potential confounders. MAIN OUTCOME
      MEASURE: We measured serum 25(OH)D levels below 10 ng/ml. RESULTS: A total of 181
      individuals (0.9% of the population) used steroids within the past 30 d. Overall,
      5% of the population had 25(OH)D levels below 10 ng/ml. Among steroid users, 11%
      had 25(OH)D levels below 10 ng/ml, compared to 5% among steroid nonusers (P =
      0.009). The odds of having 25(OH)D deficiency were 2-fold higher in those who
      reported steroid use compared to those without steroid use [odds ratio (OR),
      2.36; 95% confidence interval (CI), 1.25, 4.45]. This association remained after
      multivariable adjustment (OR, 2.21; 95% CI, 1.01, 4.85) and in a multivariable
      model using NHANES III data (OR, 1.88; 95% CI, 1.01, 3.48). CONCLUSION: Steroid
      use is independently associated with 25(OH)D deficiency in this nationally
      representative cohort limited by cross-sectional data. It suggests the need for
      screening and repletion in patients on chronic steroids.

PMID- 21956425
TI  - Reduced gluteal expression of adipogenic and lipogenic genes in Black South
      African women is associated with obesity-related insulin resistance.
AB  - CONTEXT: Black South African women are less insulin sensitive than their White
      counterparts, despite less central and greater peripheral fat deposition. We
      hypothesized that this paradox may be explained, in part, by differences in the
      adipogenic capacity of sc adipose tissue (SAT). OBJECTIVE: Our objective was to
      measure adipogenic and lipogenic gene expression in abdominal and gluteal SAT
      depots and determine their relationships with insulin sensitivity (S(I)) in South
      African women. PARTICIPANTS AND DESIGN: Fourteen normal-weight [body mass index
      (BMI) <25 kg/m(2)] Black, 13 normal-weight White, 14 obese (BMI >30 kg/m(2))
      Black, and 13 obese White premenopausal South African women participated in this
      cross-sectional study. MAIN OUTCOMES: S(I) (frequently sampled i.v. glucose
      tolerance test) in relation to expression of adipogenic and lipogenic genes in
      abdominal and gluteal SAT depots. RESULTS: With increasing BMI, Black women had
      less visceral fat (P = 0.03) and more abdominal (P = 0.017) and gynoid (P =
      0.041) SAT but had lower S(I) (P < 0.01) than White women. The expression of
      adipogenic and lipogenic genes was proportionately lower with obesity in Black
      but not White women in the gluteal and deep SAT depots (P < 0.05 for ethnicity *
      BMI effect). In Black women only, the expression of these genes correlated
      positively with S(I) (all P < 0.05), independently of age and fat mass.
      CONCLUSIONS: Obese Black women have reduced SAT expression of adipogenic and
      lipogenic genes compared with White women, which associates with reduced S(I).
      These findings suggest that obesity in Black women impairs SAT adipogenesis and
      storage, potentially leading to insulin resistance and increased risk of type 2
      diabetes.

PMID- 21956426
TI  - Iodine status of pregnant and postpartum Japanese women: effect of iodine intake
      on maternal and neonatal thyroid function in an iodine-sufficient area.
AB  - BACKGROUND: Iodine deficiency in pregnant and lactating women results in serious
      damage to their fetuses, newborns, and weaning infants. The effect of dietary
      iodine intake on maternal and infantile thyroid function has not been well
      studied in iodine-sufficient areas, and there are few data on appropriate
      gestational age-specific reference ranges for urinary iodine excretion during
      pregnancy and lactation. OBJECTIVES: The aim of the study was to characterize the
      gestational change of urinary iodine excretion in Japanese women and to assess
      the effects of iodine status on thyroid function in mother and infant. METHODS: A
      total of 934 Japanese women and their 722 newborn infants were enrolled in the
      study. Iodine and creatinine concentrations were determined in spot urine samples
      in the three trimesters of pregnancy and the postpartum period at 34.0 d after
      delivery. Serum thyroperoxidase antibody and thyroglobulin antibody, TSH, and
      free T(4) were measured in each trimester, and neonatal TSH was measured on
      postnatal d 4. RESULTS: The overall median urinary iodine concentration (UIC)
      during pregnancy was 219.0 MUg/liter, higher than that in postpartum women (135.0
      MUg/liter). The prevalence of pregnant women with low UIC less than 100 MUg/liter
      or high UIC greater than 500 MUg/liter was 16.1 and 22.2%, respectively. Urinary
      iodine excretion decreased from 221.0 MUg/liter in the first trimester to 208.0
      MUg/liter in the second trimester to 193.0 MUg/liter in the third trimester, and
      then remained at 135.0 MUg/liter postpartum. [corrected]. The maternal UIC
      correlated positively with serum TSH during pregnancy. There was no significant
      difference in UIC between subjects with positive thyroid autoantibodies and those
      with negative antibodies. CONCLUSIONS: Iodine intake assessed by UIC in Japanese
      pregnant women is regarded as sufficient and not excessive according to World
      Health Organization criteria. Although the data are local, our results provide
      additional information on the reference range for UIC throughout gestation in
      iodine-sufficient areas.

PMID- 21956427
TI  - MicroRNA 135 regulates HOXA10 expression in endometriosis.
AB  - CONTEXT: Homeo box A10 (HOXA10) regulates endometrial receptivity and its
      expression is decreased in women with endometriosis. Although sex steroids
      regulate HOXA10, these hormones are unaltered in endometriosis. We hypothesized a
      role for microRNA in the regulation of HOXA10. OBJECTIVE: MicroRNA 135a and -b
      are small noncoding RNA with predicted targets that include HOXA10. We evaluated
      miR135a/b expression and HOXA10 regulation in endometrium from subjects with and
      without endometriosis. DESIGN: The design of the study was the measurement of
      miR135a/b expression by quantitative PCR and in vitro analysis of HOXA10
      regulation. SETTING: The study was conducted at a university medical center.
      PATIENTS: Patients included 50 controls and 32 women with endometriosis.
      INTERVENTIONS: Study interventions included endometrial biopsies and in vitro
      transfection. MAIN OUTCOME MEASURES: miR135a/b and HOXA10 expression were
      measured in the study. RESULTS: All endometrial samples expressed miR135a and -b.
      miR135a expression in controls was increased during the proliferative phase,
      decreased at the time of ovulation, and increased during the luteal phase.
      Subjects with endometriosis had 3-fold higher expression of miR135a in the
      proliferative phase than controls. miR135b showed less variation across the
      menstrual cycle; however, it was significantly increased in women with
      endometriosis in the proliferative and secretory phases. HOXA10 expression was
      simultaneously repressed in the endometrium of women with endometriosis.
      Transfection of endometrial stromal cells with mir135a/b or miR135a/b inhibitors
      resulted in the altered expression of HOXA10 mRNA and protein. miR135a or -b
      decreased luciferase expression driven by the HOXA10 3' untranslated region
      containing the miR135 binding site. miR135a regulation of HOXA10 was absent in
      MCF-7 cells, demonstrating cell specificity. CONCLUSIONS: HOXA10 was aberrantly
      regulated in the endometrium of women with endometriosis by both miR135a and
      miR135b. Increased microRNA expression likely suppresses genes required for
      implantation.

PMID- 21956428
TI  - Spermatophoric reaction reappraised: novel insights into the functioning of the
      loliginid spermatophore based on Doryteuthis plei (Mollusca: Cephalopoda).
AB  - During copulation, spermatophores produced by male coleoid cephalopods undergo
      the spermatophoric reaction, a complex process of evagination that culminates in
      the attachment of the spermatangium (everted spermatophore containing the sperm
      mass) on the female's body. To better understand this complicated phenomenon, the
      present study investigated the functional morphology of the spermatophore of the
      squid Doryteuthis plei applying in vitro analysis of the reaction, as well as
      light and electron microscopy investigation of spermatangia obtained either in
      vitro, or naturally attached on females. Hitherto unnoticed functional features
      of the loliginid spermatophore require a reappraisal of some important processes
      involved in the spermatophoric reaction. The most striking findings concern the
      attachment mechanism, which is not carried out solely by cement adhesive
      material, as previously believed, but rather by an autonomous, complex process
      performed by multiple structures during the spermatophoric reaction. During
      evagination, the ejaculatory apparatus provides anchorage on the targeted tissue,
      presumably due to the minute stellate particles present in the exposed spiral
      filament. Consequently, the ejaculatory apparatus maintains the attachment of the
      tip of the evaginating spermatophore until the cement body is extruded.
      Subsequently, the cement body passes through a complex structural rearrangement,
      which leads to the injection of both its viscid contents and pointed oral region
      onto the targeted tissue. The inner membrane at the oral region of the cement
      body contains numerous stellate particles attached at its inner side; eversion of
      this membrane exposes these sharp structures, which presumably adhere to the
      tissue and augment attachment. Several naturally attached spermatangia were found
      with their bases implanted at the deposition sites, and the possible mechanisms
      of perforation are discussed based on present evidence. The function of the
      complex squid spermatophore and its spermatophoric reaction is revisited in light
      of these findings. J. Morphol. 2012. (c) 2011 Wiley Periodicals, Inc.

PMID- 21956430
TI  - Neoadjuvant treatment of duodenal adenocarcinoma: a rescue strategy.
AB  - AIM: To evaluate the role of neoadjuvant chemoradiation therapy and rescue
      surgery in the management of unresectable or recurrent duodenal adenocarcinoma.
      METHODS: Retrospective review of all adults treated with neoadjuvant therapy and
      rescue surgery for locally unresectable or locally recurrent duodenal
      adenocarcinoma from 1994 to 2010. RESULTS: Ten patients received various forms of
      neoadjuvant therapy prior to operative exploration for potential resection. Six
      patients presented with locally unresectable disease, while four had local
      recurrences. Six patients had vascular encasement, three had retroperitoneal
      extension with vascular invasion, and one had invasion of surrounding organs. Of
      the six patients with locally advanced disease, preoperative therapy consisted of
      chemotherapy alone (3) or chemoradiotherapy (3). Of the four patients with local
      recurrences, preoperative therapy consisted of chemotherapy alone (1),
      chemoradiotherapy alone (1), chemoradiotherapy after chemotherapy (1), and
      chemoradiotherapy followed by combination chemotherapy (1). Nine of ten patients
      became resectable after neoadjuvant therapy. Clinically, two patients had
      complete responses, and four had partial responses. Histopathology revealed
      complete pathologic response in two patients and near-complete pathologic
      response in one (<1 mm of residual disease). Currently, five patients are alive
      (range 18-83 months postoperatively). All have no evidence of disease.
      CONCLUSION: Neoadjuvant therapy may convert locally unresectable duodenal
      adenocarcinoma to resectable disease with subsequent prolonged survival.

PMID- 21956429
TI  - Prediction of high-valent iron K-edge absorption spectra by time-dependent
      density functional theory.
AB  - In recent years, a number of high-valent iron intermediates have been identified
      as reactive species in iron-containing metalloproteins. Inspired by the interest
      in these highly reactive species, chemists have synthesized Fe(IV) and Fe(V)
      model complexes with terminal oxo or nitrido groups, as well as a rare example of
      an Fe(VI)-nitrido species. In all these cases, X-ray absorption spectroscopy has
      played a key role in the identification and characterization of these species,
      with both the energy and intensity of the pre-edge features providing
      spectroscopic signatures for both the oxidation state and the local site
      geometry. Here we build on a time-dependent DFT methodology for the prediction of
      Fe K- pre-edge features, previously applied to ferrous and ferric complexes, and
      extend it to a range of Fe(IV), Fe(V) and Fe(VI) complexes. The contributions of
      oxidation state, coordination environment and spin state to the spectral features
      are discussed. These methods are then extended to calculate the spectra of the
      heme active site of P450 Compound II and the non-heme active site of TauD. The
      potential for using these methods in a predictive manner is highlighted.

PMID- 21956431
TI  - Intraoperative real-time cholangiography and C-tube drainage in donor hepatectomy
      reduce biliary tract complications.
AB  - BACKGROUND: In living-donor liver transplantation, biliary tract complications
      are a serious problem for recipients and donors. METHODS: We applied
      intraoperative real-time cholangiography using a C-arm and/or C-tube drainage to
      reduce biliary tract complications in donor hepatectomy. From 2003 to 2010,
      intraoperative real-time cholangiography and C-tube drainage was applied to 39
      and 19 donor cases, respectively. Fifteen donor cases had both procedures.
      RESULTS: We confirmed the division line of the hepatic duct by visualizing a
      stricture on the monitor of the C-arm by pulling a thread and dissecting the
      proper site of the bile duct. The number of hepatic ducts of the graft to be
      anastomosed was 1 in 11 cases and 2 or 3 in 8 of the 19 cases without
      intraoperative real-time cholangiography, and it was 1 in 32 cases and 2 in 7 of
      the 39 cases with intraoperative real-time cholangiography. Bile leakage from the
      resection occurred in seven donors without, and in none of those with, C-tube
      drainage. CONCLUSION: In living-donor liver transplantation, intraoperative real
      time cholangiography enables effective determination of the precise division line
      of the hepatic duct. Moreover, C-tube drainage is effective for reducing bile
      leakage from the resected surface of the liver of donors.

PMID- 21956432
TI  - Thirty-day outcomes in patients treated with en bloc colectomy and pancreatectomy
      for locally advanced carcinoma of the colon.
AB  - OBJECTIVE: The aim of this was to define 30-day outcomes of patients treated with
      colectomy and en bloc pancreatectomy for invasive colon cancer. METHODS: ACS
      NSQIP was used to identify patients who underwent colectomy and pancreatectomy
      concomitantly (n = 65) for colon carcinoma. Patients with en bloc pancreatectomy
      were compared to a propensity score-matched control group for 30-day outcomes.
      RESULTS: Sixteen patients underwent a pancreaticoduodenectomy with colectomy and
      49 patients underwent a distal pancreatectomy with colectomy. There were 195
      matched control patients. En bloc pancreatectomy (Whipple vs. distal
      pancreatectomy vs. control) patients had longer OR times (390 vs. 265 vs.137 min)
      and length of postoperative stay (12 vs. 10 vs. 6 days). The frequency of
      pulmonary complications (31.3% vs. 36.7% vs. 3.6%), blood transfusions (2.9 vs.
      1.7 vs. 0.3 U), wound dehiscence, (18.8% vs. 6.12% vs.0.5%) and surgical site
      infection (43.5% vs. 34.7% vs.14.9%) were substantially higher in the
      pancreatectomy group (p < 0.05). There were no statistically significant
      differences in 30-day mortality between the pancreatectomy group and the control
      group (6.3% vs. 0% vs. 1.5% p = 0.25) CONCLUSIONS: Perioperative outcomes with en
      bloc pancreatectomy and colectomy include increased pulmonary complications,
      blood transfusions, wound complications, and length of stay compared to patients
      treated with colectomy alone for colon cancer.

PMID- 21956434
TI  - Neoadjuvant radiochemotherapy in adenocarcinoma of the esophagus: ERCC1 gene
      polymorphisms for prediction of response and prognosis.
AB  - INTRODUCTION: Neoadjuvant radiochemotherapy (RT/CTx) regimens were primarily
      designed for treatment of squamous cell carcinoma of the esophagus. Own
      preliminary results demonstrate that also patients with locally advanced
      adenocarcinoma of the esophagus may achieve a major response in 30% with a 3-year
      survival rate of 80%. To identify these patients, ERCC1 (rs11615) gene
      polymorphisms were analyzed. ERCC1 is a key enzyme of the nucleotide excision and
      repair (NER) complex to prevent DNA inter- and intra-strand crosslinks. PATIENTS
      AND METHODS: Genomic DNA from 217 patients with cT3/4 adenocarcinoma of the
      esophagus was extracted from paraffin-embedded tissues. Of these patients, 153
      underwent neoadjuvant RT/CTx (CDDP, 5-FU, 36 Gy). For analysis of ERCC1 single
      nucleotide polymorphisms (SNPs), allelic discrimination was performed by
      quantitative real-time PCR. Two allele-specific TaqMan probes in competition were
      used for amplification of ERCC1 (rs11615). Allelic genotyping was correlated with
      histomorphologic tumor regression after neoadjuvant RT/CTx and survival. Major
      response (MaHR) was defined as <10% vital residual tumor cells (VRTC). RESULTS:
      Analysis of tumor regression revealed a MaHR in 56/153 (36.6%) patients with a 5
      year survival rate (5-YSR) of 74% (p < 0.001). ERCC1 gene polymorphisms for all
      patients showed the following expression pattern: ERCC1 polymorphism (rs11615)
      CC: n = 27 (12.4%), TT: n = 98 (45.2%), C/T: n = 92 (42.4%). ERCC1 polymorphism
      CT was identified as a predictor for response to the neoadjuvant RT/CTx (p <
      0.001). The 5-YSR for patients with C/T genotype was 51%. Contrary to this, the 5
      YSR for the group of patients with a CC/TT polymorphism decreased to 34%.
      CONCLUSION: Analysis of ERCC1 (rs11615) gene polymorphisms reveals a significant
      correlation with response and survival in patients with adenocarcinoma of the
      esophagus treated with a neoadjuvant radiochemotherapy. Single nucleotide
      polymorphisms of ERCC1 (rs11615) could therefore be applied to further
      individualize therapy in esophageal cancer.

PMID- 21956435
TI  - Allergic predisposition, histamine and histamine receptor expression (H1R, H2R)
      are associated with complicated courses of sigmoid diverticulitis.
AB  - BACKGROUND: We aimed to evaluate our hypothesis that allergic predisposition and
      expression of histamine receptors might contribute to complicated courses of
      sigmoid diverticulitis. METHODS: Expression of histamine and histamine receptors
      (H1R, H2R) was analysed on protein level (immunohistochemistry/immunofluorescence
      (IF)) as well as mRNA level (reverse transcription-PCR (RT-PCR) in surgical
      specimen of patients (n = 101) having undergone resection for sigmoid
      diverticulits (n = 57 complicated diverticulitis/n = 44 non-complicated
      diverticulitis). RESULTS: The mean number of comorbid diseases per patient was
      1.76 +/- 1.25. Thirty-nine of 101 patients (38.6%) exhibited allergic
      predisposition (grass poll, food, drug, pets, etc.). Comorbid diseases were
      significantly associated with complicated diverticulitis (p = 0.027). Complicated
      sigmoid diverticulitis was significantly associated with high H1R and H2R
      expression (p < 0.001). Furthermore, an association of complicated diverticulitis
      with allergic predisposition was found (odds ratio = 3.2, p = 0.0097). IF double
      labelling experiments showed a strong correlation of increased histamine
      expression with expression of H1R and H2R on intestinal enterocytes
      (histamine/H1R, rho = 0.841, p < 0.0001 and histamine/H2R, rho = 0.806, p <
      0.0001). The results of increased H1R and H2R expression in complicated sigmoid
      diverticulitis were also detected on mRNA level in a subset of patients (RT-PCR,
      p = 0.009). CONCLUSIONS: Our findings suggest that allergic predisposition might
      be another important risk factor for complicated courses of acute sigmoid
      diverticulitis and linked with histamine receptor expression. Supportive
      therapies with antihistaminic drugs might become an option. Allergic
      predisposition might be worth considering when indicating surgery for sigmoid
      diverticulitis.

PMID- 21956436
TI  - Hybrid magnetic/superconducting materials obtained by insertion of a single
      molecule magnet into TaS2 layers.

PMID- 21956437
TI  - Implementation of renormalized excitonic method at ab initio level.
AB  - The renormalized excitonic method [Hajj et al., Phys Rev B 2005, 72, 224412], in
      which the excited state of the whole system may be described as a linear
      combination of local excitations, has been implemented at ab initio level. Its
      performance is tested on the ionization potential and the energy gap between
      singlet ground state and lowest triplet for linear molecular hydrogen chains and
      more realistic systems, such as polyenes and polysilenes, using full
      configuration interaction (FCI) wave functions with a minimal basis set. The
      influence of different block sizes and the extent of interblock interactions are
      investigated. It has been demonstrated that satisfactory results can be obtained
      if the near degeneracies between the model space and the outer space are avoided
      and if interactions between the next-nearest neighbor blocks are considered. The
      method can be used with larger basis sets and other accurate enough ab initio
      evaluations (instead of FCI) of local excited states, from blocks, or from dimers
      or trimers of blocks. It provides a new possibility to accurately and
      economically describe the low-lying delocalized excited states of large systems,
      even inhomogeneous ones.

PMID- 21956438
TI  - Subjective and neural responses to intravenous alcohol in young adults with light
      and heavy drinking patterns.
AB  - Heavy alcohol consumption during young adulthood is a risk factor for the
      development of serious alcohol use disorders. Research has shown that individual
      differences in subjective responses to alcohol may affect individuals'
      vulnerability to developing alcoholism. Studies comparing the subjective and
      objective response to alcohol between light and heavy drinkers (HDs), however,
      have yielded inconsistent results, and neural responses to alcohol in these
      groups have not been characterized. We performed a double-blind, placebo
      controlled, randomized crossover alcohol challenge study comparing functional
      magnetic resonance imaging and subjective response to intravenously administered
      6% v/v ethanol to a target blood alcohol concentration of 0.08% or placebo
      between HDs and social drinkers (SDs). During the imaging, we presented emotional
      cues in order to measure how emotion modulated the effects of alcohol on the
      brain's reward circuitry. We found that, at equivalent blood alcohol
      concentrations, HDs reported lower subjective alcohol effects than SDs. Alcohol
      significantly activated the nucleus accumbens in SDs, but not in HDs. Self
      reported ratings of intoxication correlated with striatal activation, suggesting
      that activation may reflect subjective experience of intoxication. Fearful faces
      significantly activated the amygdala in the SDs only, and this activation was
      attenuated by alcohol. This study shows that HDs not only experience reduced
      subjective effects of alcohol, but also demonstrate a blunted response to alcohol
      in the brain's reward system. Our findings indicate that reduced subjective and
      neural response to alcohol in HDs may be suggestive of either the development of
      tolerance to alcohol, or of pre-existing decreased sensitivity to alcohol's
      effects.

PMID- 21956439
TI  - Genome-wide association study of alcohol dependence implicates KIAA0040 on
      chromosome 1q.
AB  - Previous studies using SAGE (the Study of Addiction: Genetics and Environment)
      and COGA (the Collaborative Study on the Genetics of Alcoholism) genome-wide
      association study (GWAS) data sets reported several risk loci for alcohol
      dependence (AD), which have not yet been well replicated independently or
      confirmed by functional studies. We combined these two data sets, now publicly
      available, to increase the study power, in order to identify replicable,
      functional, and significant risk regions for AD. A total of 4116 subjects (1409
      European-American (EA) cases with AD, 1518 EA controls, 681 African-American (AA)
      cases, and 508 AA controls) underwent association analysis. An additional 443
      subjects underwent expression quantitative trait locus (eQTL) analysis. Genome
      wide association analysis was performed in EAs to identify significant risk
      genes. All available markers in the genome-wide significant risk genes were
      tested in AAs for associations with AD, and in six HapMap populations and two
      European samples for associations with gene expression levels. We identified a
      unique genome-wide significant gene--KIAA0040--that was enriched with many
      replicable risk SNPs for AD, all of which had significant cis-acting regulatory
      effects. The distributions of -log(p) values for SNP-disease and SNP-expression
      associations for all markers in the TNN-KIAA0040 region were consistent across
      EAs, AAs, and five HapMap populations (0.369 <= r <= 0.824; 2.8 * 10-9 <= p <=
      0.032). The most significant SNPs in these populations were in high LD,
      concentrating in KIAA0040. Finally, expression of KIAA0040 was significantly (1.2
      * 10-11 <= p <=1 .5 * 10-6) associated with the expression of numerous genes in
      the neurotransmitter systems or metabolic pathways previously associated with AD.
      We concluded that KIAA0040 might harbor a causal variant for AD and thus might
      directly contribute to risk for this disorder. KIAA0040 might also contribute to
      the risk of AD via neurotransmitter systems or metabolic pathways that have
      previously been implicated in the pathophysiology of AD. Alternatively, KIAA0040
      might regulate the risk via some interactions with flanking genes TNN and TNR.
      TNN is involved in neurite outgrowth and cell migration in hippocampal explants,
      and TNR is an extracellular matrix protein expressed primarily in the central
      nervous system.

PMID- 21956440
TI  - Investigation of anatomical thalamo-cortical connectivity and FMRI activation in
      schizophrenia.
AB  - The purpose of this study was to examine measures of anatomical connectivity
      between the thalamus and lateral prefrontal cortex (LPFC) in schizophrenia and to
      assess their functional implications. We measured thalamocortical connectivity
      with diffusion tensor imaging (DTI) and probabilistic tractography in 15 patients
      with schizophrenia and 22 age- and sex-matched controls. The relationship between
      thalamocortical connectivity and prefrontal cortical blood-oxygenation-level
      dependent (BOLD) functional activity as well as behavioral performance during
      working memory was examined in a subsample of 9 patients and 18 controls.
      Compared with controls, schizophrenia patients showed reduced total connectivity
      of the thalamus to only one of six cortical regions, the LPFC. The size of the
      thalamic region with at least 25% of model fibers reaching the LPFC was also
      reduced in patients compared with controls. The total thalamocortical
      connectivity to the LPFC predicted working memory task performance and also
      correlated with LPFC BOLD activation. Notably, the correlation with BOLD
      activation was accentuated in patients as compared with controls in the ventral
      LPFC. These results suggest that thalamocortical connectivity to the LPFC is
      altered in schizophrenia with functional consequences on working memory
      processing in LPFC.

PMID- 21956441
TI  - Nicotine improves working memory span capacity in rats following sub-chronic
      ketamine exposure.
AB  - Ketamine, an NMDA-receptor antagonist, produces cognitive deficits in humans in a
      battery of tasks involving attention and memory. Nicotine can enhance various
      indices of cognitive performance, including working memory span capacity measured
      using the odor span task (OST). This study examined the effects of a sub-chronic
      ketamine treatment to model cognitive deficits associated with schizophrenia, and
      to evaluate the effectiveness of nicotine, antipsychotic clozapine, and the novel
      mGlu2/3 agonist, LY404039, in restoring OST performance. Male hooded Lister rats
      were trained in the OST, a working memory task involving detection of a novel
      odor from an increasing number of presented odors until they exhibited asymptotic
      levels of stable performance. Sub-chronic ketamine exposure (10 and 30 mg/kg i.p.
      for 5 consecutive days) produced a dose-dependent impairment that was stable
      beyond 14 days following exposure. In one cohort, administration of graded doses
      of nicotine (0.025-0.1 mg/kg) acutely restored the performance in ketamine
      treated animals, while significant improvements in odor span were observed in
      control subjects. In a second cohort of rats, acute tests with clozapine (1-10
      mg/kg) and LY404039 (0.3-10 mg/kg) failed to reverse ketamine-induced deficits in
      doses that were observed to impair performance in the control groups. These data
      suggest that sub-chronic ketamine exposure in the OST presents a valuable method
      to examine novel treatments to restore cognitive impairments associated with
      neuropsychiatric disorders such as schizophrenia. Moreover, it highlights a
      central role for neuronal nicotinic receptors as viable targets for intervention
      that may be useful adjuncts to the currently prescribed anti-psychotics.

PMID- 21956444
TI  - The methylazoxymethanol acetate (MAM-E17) rat model: molecular and functional
      effects in the hippocampus.
AB  - Administration of the DNA-alkylating agent methylazoxymethanol acetate (MAM) on
      embryonic day 17 (E17) produces behavioral and anatomical brain abnormalities,
      which model some aspects of schizophrenia. This has lead to the premise that MAM
      rats are a neurodevelopmental model for schizophrenia. However, the underlying
      molecular pathways affected in this model have not been elucidated. In this
      study, we investigated the molecular phenotype of adult MAM rats by focusing on
      the frontal cortex and hippocampal areas, as these are known to be affected in
      schizophrenia. Proteomic and metabonomic analyses showed that the MAM treatment
      on E17 resulted primarily in deficits in hippocampal glutamatergic
      neurotransmission, as seen in some schizophrenia patients. Most importantly,
      these results were consistent with our finding of functional deficits in
      glutamatergic neurotransmission, as identified using electrophysiological
      recordings. Thus, this study provides the first molecular evidence, combined with
      functional validation, that the MAM-E17 rat model reproduces hippocampal deficits
      relevant to the pathology of schizophrenia.

PMID- 21956445
TI  - Effects of chronic marijuana use on brain activity during monetary decision
      making.
AB  - Marijuana (MJ) acutely acts on cannabinoid receptors that are found in numerous
      brain regions, including those involved in reward processing and decision-making.
      However, it remains unclear how long-term, chronic MJ use alters reward-based
      decision-making. In the present study, using [(15)O]water PET imaging, we
      measured brain activity in chronic MJ users, who underwent monitored abstinence
      from MJ for approximately 24 h before imaging, and control participants, while
      they took part in the Iowa Gambling Task (IGT), a monetary decision making task
      that strongly relies on the ventromedial prefrontal cortex (vmPFC). During PET
      imaging, participants took part in the standard and a variant version of the IGT
      as well as a control task. Chronic MJ users performed equally well on the
      standard IGT, but significantly worse than controls on the variant IGT. Chronic
      MJ users and control subjects showed increased regional cerebral blood flow
      (rCBF) in the vmPFC on both versions of the IGT compared to the control task. In
      the two-group comparison, chronic MJ users showed significantly greater rCBF than
      controls in the vmPFC on the standard IGT and greater activity in the cerebellum
      on both versions of the IGT. Furthermore, duration of use, but not age of first
      use, was associated with greater activity in the vmPFC. Thus, chronic MJ users
      tend to strongly recruit neural circuitry involved in decision-making and reward
      processing (vmPFC), and probabilistic learning (cerebellum) when performing the
      IGT.

PMID- 21956443
TI  - Muscarinic and nicotinic acetylcholine receptor agonists and allosteric
      modulators for the treatment of schizophrenia.
AB  - Muscarinic and nicotinic acetylcholine (ACh) receptors (mAChRs and nAChRs) are
      emerging as important targets for the development of novel treatments for the
      symptoms associated with schizophrenia. Preclinical and early proof-of-concept
      clinical studies have provided strong evidence that activators of specific mAChR
      (M(1) and M(4)) and nAChR (alpha(7) and alpha(2)beta(4)) subtypes are effective
      in animal models of antipsychotic-like activity and/or cognitive enhancement, and
      in the treatment of positive and cognitive symptoms in patients with
      schizophrenia. While early attempts to develop selective mAChR and nAChR agonists
      provided important preliminary findings, these compounds have ultimately failed
      in clinical development due to a lack of true subtype selectivity and subsequent
      dose-limiting adverse effects. In recent years, there have been major advances in
      the discovery of highly selective activators for the different mAChR and nAChR
      subtypes with suitable properties for optimization as potential candidates for
      clinical trials. One novel strategy has been to identify ligands that activate a
      specific receptor subtype through actions at sites that are distinct from the
      highly conserved ACh-binding site, termed allosteric sites. These allosteric
      activators, both allosteric agonists and positive allosteric modulators, of mAChR
      and nAChR subtypes demonstrate unique mechanisms of action and high selectivity
      in vivo, and may provide innovative treatment strategies for schizophrenia.

PMID- 21956442
TI  - Parkinson's disease therapeutics: new developments and challenges since the
      introduction of levodopa.
AB  - The demonstration that dopamine loss is the key pathological feature of
      Parkinson's disease (PD), and the subsequent introduction of levodopa have
      revolutionalized the field of PD therapeutics. This review will discuss the
      significant progress that has been made in the development of new pharmacological
      and surgical tools to treat PD motor symptoms since this major breakthrough in
      the 1960s. However, we will also highlight some of the challenges the field of PD
      therapeutics has been struggling with during the past decades. The lack of
      neuroprotective therapies and the limited treatment strategies for the nonmotor
      symptoms of the disease (ie, cognitive impairments, autonomic dysfunctions,
      psychiatric disorders, etc.) are among the most pressing issues to be addressed
      in the years to come. It appears that the combination of early PD nonmotor
      symptoms with imaging of the nigrostriatal dopaminergic system offers a promising
      path toward the identification of PD biomarkers, which, once characterized, will
      set the stage for efficient use of neuroprotective agents that could slow down
      and alter the course of the disease.

PMID- 21956446
TI  - From revolution to evolution: the glutamate hypothesis of schizophrenia and its
      implication for treatment.
AB  - Glutamate is the primary excitatory neurotransmitter in mammalian brain.
      Disturbances in glutamate-mediated neurotransmission have been increasingly
      documented in a range of neuropsychiatric disorders including schizophrenia,
      substance abuse, mood disorders, Alzheimer's disease, and autism-spectrum
      disorders. Glutamatergic theories of schizophrenia are based on the ability of N
      methyl-D-aspartate receptor (NMDAR) antagonists to induce schizophrenia-like
      symptoms, as well as emergent literature documenting disturbances of NMDAR
      related gene expression and metabolic pathways in schizophrenia. Research over
      the past two decades has highlighted promising new targets for drug development
      based on potential pre- and postsynaptic, and glial mechanisms leading to NMDAR
      dysfunction. Reduced NMDAR activity on inhibitory neurons leads to disinhibition
      of glutamate neurons increasing synaptic activity of glutamate, especially in the
      prefrontal cortex. Based on this mechanism, normalizing excess glutamate levels
      by metabotropic glutamate group 2/3 receptor agonists has led to potential
      identification of the first non-monoaminergic target with comparable efficacy as
      conventional antipsychotic drugs for treating positive and negative symptoms of
      schizophrenia. In addition, NMDAR has intrinsic modulatory sites that are active
      targets for drug development, several of which show promise in preclinical/early
      clinical trials targeting both symptoms and cognition. To date, most studies have
      been done with orthosteric agonists and/or antagonists at specific sites.
      However, allosteric modulators, both positive and negative, may offer superior
      efficacy with less danger of downregulation.

PMID- 21956447
TI  - Psilocybin-induced deficits in automatic and controlled inhibition are attenuated
      by ketanserin in healthy human volunteers.
AB  - The serotonin-2A receptor (5-HT(2A)R) has been implicated in the pathogenesis of
      schizophrenia and related inhibitory gating and behavioral inhibition deficits of
      schizophrenia patients. The hallucinogen psilocybin disrupts automatic forms of
      sensorimotor gating and response inhibition in humans, but it is unclear so far
      whether the 5-HT(2A)R or 5-HT(1A)R agonist properties of its bioactive metabolite
      psilocin account for these effects. Thus, we investigated whether psilocybin
      induced deficits in automatic and controlled inhibition in healthy humans could
      be attenuated by the 5-HT(2A/2C)R antagonist ketanserin. A total of 16 healthy
      participants received placebo, ketanserin (40 mg p.o.), psilocybin (260 MUg/kg
      p.o.), or psilocybin plus ketanserin in a double-blind, randomized, and
      counterbalanced order. Sensorimotor gating was measured by prepulse inhibition
      (PPI) of the acoustic startle response. The effects on psychopathological core
      dimensions and behavioral inhibition were assessed by the altered states of
      consciousness questionnaire (5D-ASC), and the Color-Word Stroop Test. Psilocybin
      decreased PPI at short lead intervals (30 ms), increased all 5D-ASC scores, and
      selectively increased errors in the interference condition of the Stroop Test.
      Stroop interference and Stroop effect of the response latencies were increased
      under psilocybin as well. Psilocybin-induced alterations were attenuated by
      ketanserin pretreatment, whereas ketanserin alone had no significant effects.
      These findings suggest that the disrupting effects of psilocybin on automatic and
      controlled inhibition processes are attributable to 5-HT(2A)R stimulation.
      Sensorimotor gating and attentional control deficits of schizophrenia patients
      might be due to changes within the 5-HT(2A)R system.

PMID- 21956450
TI  - A microenvironment-sensitive fluorescent pyrimidine ribonucleoside analogue:
      synthesis, enzymatic incorporation, and fluorescence detection of a DNA abasic
      site.
AB  - Base-modified fluorescent ribonucleoside-analogue probes are valuable tools in
      monitoring RNA structure and function because they closely resemble the structure
      of natural nucleobases. Especially, 2-aminopurine, a highly environment-sensitive
      adenosine analogue, is the most extensively utilized fluorescent nucleoside
      analogue. However, only a few isosteric pyrimidine ribonucleoside analogues that
      are suitable for probing the structure and recognition properties of RNA
      molecules are available. Herein, we describe the synthesis and photophysical
      characterization of a small series of base-modified pyrimidine ribonucleoside
      analogues derived from tagging indole, N-methylindole, and benzofuran onto the 5
      position of uracil. One of the analogues, based on a 5-(benzofuran-2
      yl)pyrimidine core, shows emission in the visible region with a reasonable
      quantum yield and, importantly, displays excellent solvatochromism. The
      corresponding triphosphate substrate is effectively incorporated into
      oligoribonucleotides by T7 RNA polymerase to produce fluorescent
      oligoribonucleotide constructs. Steady-state and time-resolved spectroscopic
      studies with fluorescent oligoribonucleotide constructs demonstrate that the
      fluorescent ribonucleoside photophysically responds to subtle changes in its
      environment brought about by the interaction of the chromophore with neighboring
      bases. In particular, the emissive ribonucleoside, if incorporated into an
      oligoribonucleotide, positively reports the presence of a DNA abasic site with an
      appreciable enhancement in fluorescence intensity. The straightforward synthesis,
      amicability to enzymatic incorporation, and sensitivity to changes in the
      microenvironment highlight the potential of the benzofuran-conjugated pyrimidine
      ribonucleoside as an efficient fluorescent probe to investigate nucleic acid
      structure, dynamics, and recognition events.

PMID- 21956448
TI  - Differential regulation of MeCP2 phosphorylation in the CNS by dopamine and
      serotonin.
AB  - Systemic administration of amphetamine (AMPH) induces phosphorylation of MeCP2 at
      Ser421 (pMeCP2) in select populations of neurons in the mesolimbocortical brain
      regions. Because AMPH simultaneously activates multiple monoamine
      neurotransmitter systems, here we examined the ability of dopamine (DA),
      serotonin (5-HT), and norepinephrine (NE) to induce pMeCP2. Selective blockade of
      the DA transporter (DAT) or the 5-HT transporter (SERT), but not the NE
      transporter (NET), was sufficient to induce pMeCP2 in the CNS. DAT blockade
      induced pMeCP2 in the prelimbic cortex (PLC) and nucleus accumbens (NAc), whereas
      SERT blockade induced pMeCP2 only in the NAc. Administration of selective DA and
      5-HT receptor agonists was also sufficient to induce pMeCP2; however, the
      specific combination of DA and 5-HT receptors activated determined the regional-
      and cell-type specificity of pMeCP2 induction. The D(1)-class DA receptor agonist
      SKF81297 induced pMeCP2 widely; however, coadministration of the D(2)-class
      agonist quinpirole restricted the induction of pMeCP2 to GABAergic interneurons
      of the NAc. Intra-striatal injection of the adenylate cyclase activator forskolin
      was sufficient to induce pMeCP2 in medium-spiny neurons, suggesting that the
      combinatorial regulation of cAMP by different classes of DA and 5-HT receptors
      may contribute to the cell-type specificity of pMeCP2 induction. Consistent with
      the regulation of pMeCP2 by multiple monoamine neurotransmitters, genetic
      disruption of any single monoamine transporter in DAT-, SERT-, and NET-knockout
      mice failed to eliminate AMPH-induced pMeCP2 in the NAc. Together, these studies
      indicate that combinatorial signaling through DA and 5-HT receptors can regulate
      the brain region- and cell-type specific pMeCP2 in the CNS.

PMID- 21956449
TI  - Depressive symptoms in junior doctors: a follow-up study on work-related
      determinants.
AB  - PURPOSE: The study investigates the long-term effects of accumulated working
      conditions on depressive symptoms in junior doctors. Drawing on the Job Demand
      Control-Support model, this study aims to identify personal and job-related
      determinants for self-reported depression in junior doctors-a professional group
      that is vulnerable to depression. METHODS: We conducted a prospective cohort
      study with measures of work characteristics and depressive symptoms over three
      time-points among hospital doctors during postgraduate specialty training in
      Germany. Participants were 415 junior doctors with full-time contract (47.5%
      women; mean age, 30.5 years). The outcome was depressive symptoms assessed with
      the Spielberger State-Depression Scale. Odds ratios (OR) were computed to analyse
      the cumulative effect of initial depressive symptoms scores, demographic
      variables, and working characteristics across T1 and T2 on subsequent depressive
      symptoms at T3. RESULTS: The percentage of junior doctors reporting depressive
      symptoms scores above a critical value varied between 12.0% at T1, 10.4% at T2,
      and 13.3% at T3; N = 34 doctors (8.19%) were classified as incident cases during
      the observation period. Elevated depressive symptoms at T3 were positively
      predicted by depressive symptoms scores across T1 and T2 (OR: 1.37; 95%
      confidence interval: 1.25-1.50) and negatively by professional tenure (0.54; 0.31
      0.96), free weekends (0.52; 0.28-0.97), and job autonomy (0.35; 0.18-0.65).
      CONCLUSIONS: After controlling for demographic and working time influences,
      findings suggest that junior doctors' perceived job autonomy is negatively
      associated with future depressive symptoms. Enhancing job control emerges as a
      promising strategy to lower the risk of depression during first years of
      professional practice.

PMID- 21956451
TI  - Expression and promoter methylation analysis of ATP-binding cassette genes in
      pancreatic cancer.
AB  - We investigated the relationship of ABCB1/MDR1, ABCC1/MRP1 and ABCG2/BCRP
      expression and promoter methylation with pancreatic cancer tumorigenesis and drug
      resistance. Gemcitabine-resistant pancreatic cancer cells, SW1990/GZ (33.3-fold
      increased resistance), were obtained by treating SW1990 cells with gemcitabine.
      The expression of ABCB1/MDR1, ABCC1/MRP1 and ABCG2/BCRP was determined by
      quantitative real-time RT-PCR in the cell lines, 3 normal pancreatic tissues, 15
      human pancreatic cancer samples and 15 adjacent tissues. Promoter methylation was
      determined in cell lines by bisulfite genomic sequencing. ABCB1/MDR1, ABCC1/MRP1
      and ABCG2/BCRP were upregulated in SW1990 and SW1990/GZ compared with normal
      pancreatic tissue, and expression in SW1990/GZ was significantly higher than in
      SW1990 cells. ABCB1/MDR1, ABCC1/MRP1 and ABCG2/BCRP were upregulated in
      pancreatic cancer tissues, compared to adjacent tissues. The ABCB1/MDR1,
      ABCC1/MRP1 and ABCG2/BCRP promoter were hypomethylated in all the cell lines.
      ABCB1/MDR1, ABCC1/MRP1 and ABCG2/BCRP expression correlated with pancreatic
      cancer tumorigenesis and drug resistance in a mechanism that is independent of
      promoter methylation.

PMID- 21956452
TI  - A multimodal approach for tracing lateralisation along the olfactory pathway in
      the honeybee through electrophysiological recordings, morpho-functional imaging,
      and behavioural studies.
AB  - Recent studies have revealed asymmetries between the left and right sides of the
      brain in invertebrate species. Here we present a review of a series of recent
      studies from our laboratories, aimed at tracing asymmetries at different stages
      along the honeybee's (Apis mellifera) olfactory pathway. These include estimates
      of the number of sensilla present on the two antennae, obtained by scanning
      electron microscopy, as well as electroantennography recordings of the left and
      right antennal responses to odorants. We describe investigative studies of the
      antennal lobes, where multi-photon microscopy was used to search for possible
      morphological asymmetries between the two brain sides. Moreover, we report on
      recently published results obtained by two-photon calcium imaging for functional
      mapping of the antennal lobe aimed at comparing patterns of activity evoked by
      different odours. Finally, possible links to the results of behavioural tests,
      measuring asymmetries in single-sided olfactory memory recall, are discussed.

PMID- 21956454
TI  - Does Tourette syndrome prevent tardive dyskinesia?

PMID- 21956453
TI  - Day-to-day discrimination and health among Asian Indians: a population-based
      study of Gujarati men and women in Metropolitan Detroit.
AB  - This study examined the relationship between experiences of day-to-day
      discrimination and two measures of health among Gujaratis, one of the largest
      ethnic groups of Asian Indians in the U.S. Data were collected via computer
      assisted telephone interviews with a random sample of Gujarati men and women aged
      18-64 in Metropolitan Detroit (N = 423). Using structural equation modeling, we
      tested two gender-moderated models of the relationship between day-to-day
      discrimination and health, one using the single-item general health status and
      the other using the 4-item emotional wellbeing measure. For both women and men,
      controlling for socio-demographic and other relevant characteristics, the
      experience of day-to-day discrimination was associated with worse emotional
      wellbeing. However, day-to-day discrimination was associated with the single-item
      self-rated general health status only for men. This study identified not only
      gender differences in discrimination-health associations but also the importance
      of using multiple questions in assessing perceived health status.

PMID- 21956455
TI  - Why do GPs with a special interest in headache investigate headache presentations
      with neuroradiology and what do they find?
AB  - The general practitioner with a special interest in headache offers an important
      contribution to the management of headache in primary care where the majority of
      presentations take place. A number of guidelines have been developed for
      neuroradiological investigation of headache, but their clinical utility and
      relevance is not known. Fourteen general practitioners with a special interest in
      headache recorded consecutive headache consultations over a 3-month period,
      whether patients were investigated with neuroradiology and if so the reason for
      investigation and outcome. Reason for investigation was compared to the
      guidelines published for the use in primary care. 895 patients were seen, of whom
      270 (30.1%) were investigated. 47% of indications were outside the guidance
      framework used, the most common reason for investigation being reassurance. Of
      those investigated, 5.6% showed positive findings but only 1.9% of findings were
      felt to be of clinical significance. General practitioners with a special
      interest investigated with neuroradiology a greater level than general
      practitioners, but less than neurologists. However, yields of significant
      findings are broadly comparative across all groups. This report confirms other
      studies that suggest that even when there is a high level of clinical suspicion,
      yields of significant findings are very low.

PMID- 21956456
TI  - An intensive 5-year-long influenza vaccination campaign is effective among
      doctors but not nurses.
AB  - OBJECTIVE: To double the vaccination rates of hospital employees from 20 to 40%
      by specific interventions over a 5-year period (2003-2007). The secondary
      endpoint was to compare the effects of the avian influenza in 2005 (intervention
      period) and the H1N1 influenza pandemic in 2009 (follow-up period, 2008-2009) on
      vaccination rates. DESIGN, SETTING, AND PARTICIPANTS: Free vaccination and its
      intensive propagation from 2003-2007 in a 400-bed teaching hospital with 1,687
      hospital employees. Annual vaccination rates were obtained from 2003 through
      2009. MAIN OUTCOME MEASUREMENTS: Yearly vaccination rates for the intervention
      period from 2003-2007 and the observational follow-up period of 2008-2009.
      RESULTS: The overall rate for seasonal influenza vaccination changed non
      significantly during the intervention period from 20% in 2003 to 27% in 2007. At
      the end of the follow-up period in 2009, the vaccination rate was 26%, which was
      not significantly higher compared with that in 2003. Physicians interestingly
      increased from 34% in 2003 to 62% in 2007 and to 66% in 2009 (p < 0.001), while
      nurses dropped non-significantly from an already low proportion of 18% in 2003 to
      15% in 2007 and to 16% in 2009 for seasonal influenza vaccination. The difference
      between nurses and doctors in 2007 is highly significant (p < 0.001). In the year
      of the avian influenza threat (2005), a significant increase was observed (30 vs.
      20%, p < 0.001). This observation was seen again in 2009 (influenza A/H1N1v
      pandemic), during which the H1N1 vaccine uptake was 33% (p < 0.001, compared to
      seasonal flu vaccine in 2003). CONCLUSIONS: Overall, the vaccination rates did
      not increase over the 7-year study period. Interventions were successful for
      physicians but not for nurses. The vaccine uptake was significantly higher during
      the threat of avian influenza and the influenza A/H1N1v pandemic.

PMID- 21956457
TI  - Conformational control of cofactors in nature--functional tetrapyrrole
      conformations in the photosynthetic reaction centers of purple bacteria.
AB  - Chemically identical tetrapyrrole cofactors such as hemes and chlorophylls
      participate in functionally diverse biological roles. An analysis of the
      available protein structural data for the bacteriochlorophylls in the
      photosynthetic reaction center gives statistically reliable evidence of the
      hypothesis that the protein induced cofactor conformation is a modulator of the
      bio-molecular function of each reaction center. The results serve as a general
      model to illustrate conformational control of tetrapyrrole cofactors in other
      proteins.

PMID- 21956458
TI  - Synthesis and biological evaluation of novel (thio)urea derivatives as potential
      antitumor agents.
AB  - A series of novel (thio)ureas containing the pyrimidinyl group was designed and
      synthesized. Their in-vitro antitumor activity against different human tumor
      cells was examined. Some of the compounds showed potential antitumor activity,
      which provided some hints for further studies on structure modification.

PMID- 21956459
TI  - Association study of brain-derived neurotrophic factor gene polymorphisms and
      body weight change in schizophrenic patients under long-term atypical
      antipsychotic treatment.
AB  - Schizophrenic patients treated with atypical antipsychotics (AAPs) often develop
      excessive body weight gain, which may lead to further morbidity and poor
      treatment compliance. This study examined whether genetic variants in the brain
      derived neurotrophic factor (BDNF) gene may be associated with body weight change
      after AAP treatment. The study included 481 schizophrenic patients treated with
      clozapine (n = 266), olanzapine (n = 79), or risperidone (n = 136) for an average
      of 49.2 +/- 28.2 months. Three common single-nucleotide polymorphisms (SNPs) of
      the BDNF gene were chosen as tagging SNPs. In single-marker-based analysis, the
      BDNF rs11030101-T homozygous genotype was found to be associated with
      significantly increased body weight gain (P = 0.037). The BDNF Val66Met (rs6265)
      polymorphism was not found to be associated with body weight gain. Haplotype
      analysis further showed that the rs11030101-T-allele-related haplotype is also
      associated with increased body weight gain (P = 0.047). Our findings suggest that
      there is a nominal association with rs11030101 but did not replicate the
      previously found relationship between the BDNF Val66Met polymorphism and body
      weight gain during long-term AAP treatment.

PMID- 21956460
TI  - Higher premenarcheal bone mass in elite gymnasts is maintained into young
      adulthood after long-term retirement from sport: a 14-year follow-up.
AB  - Sports that impact-load the skeleton during childhood and adolescence increase
      determinants of bone strength such as bone mineral content and density; however,
      it is unclear if this benefit is maintained after retirement from the sport. The
      purpose of this study was to assess whether the previously reported higher bone
      mass in a group of premenarcheal gymnasts was still apparent 10 years after the
      cessation of participation and withdrawal of the gymnastics loading stimulus. In
      1995, 30 gymnasts 8 to 15 years of age were measured and compared with 30 age
      matched nongymnasts. Twenty-five former gymnasts and 22 nongymnasts were measured
      again 14 years later (2009 to 2010). Gymnasts had been retired from gymnastics
      training and competition for an average of 10 years. Total body (TB), lumbar
      spine (LS), and femoral neck (FN) bone mineral content (BMC) was assessed at both
      measurement occasions by dual-energy X-ray absorptiometry (DXA). Multivariate
      analysis of covariance (MANCOVA) was used to compare former gymnasts' and
      nongymnasts' BMC while controlling for differences in body size and maturation
      (covariates: age, height, weight, and years from menarche [1995] or age at
      menarche [2009 to 2010]). Premenarcheal gymnasts (measured in 1995) had
      significantly greater size-adjusted TB, LS, and FN BMC (p < 0.05) (15%, 17%, and
      12%, respectively) than nongymnasts. Ten years after retirement, gymnasts had
      maintained similar size-adjusted TB, LS, and FN BMC differences (p < 0.05) (13%,
      19%, and 13%, respectively) when compared with nongymnasts. Bone mass benefits in
      premenarcheal gymnasts were still apparent even after long-term (10 years)
      removal of the gymnastics loading stimulus.

PMID- 21956461
TI  - Human beta-defensin-2 controls cell cycle in malignant epithelial cells: in vitro
      study.
AB  - AIM: In the present research we analyze the mechanism of human beta-defensin-2
      (hBD-2) influence on cultured malignant epithelial cell growth. MATERIALS AND
      METHODS: The analysis of a concentration-dependent effect of recombinant hBD-2
      (rec-hBD-2) on cell growth patterns and cell cycle distribution has been
      performed in vitro with 2 cell lines (human lung adenocarcinoma A549 cells and
      human epidermoid carcinoma A431 cells) using MTT test, flow cytometry and direct
      cell counting. To study intracellular localization of hBD-2 immunocytofluorescent
      and immunocytochemical analyses were applied, and effect of hBD-2 on signal
      cascades involved in cell cycle regulation has been studied by Western blotting.
      RESULTS: According to our data, rec-hBD-2 exerts a concentration-dependent effect
      on the viability of cultured A549 and A431 cells. It causes proproliferative
      effect at concentrations below 1 nM, significant suppression of cell
      proliferation at concentration range from 10 nM to 1 MUM (p<0.05), and cell death
      at higher concentrations. Using flow cytometry we have demonstrated that hBD-2
      dependent growth suppression is realized via cell cycle arrest at G1/S phase
      (p<0.05). Also, we have registered significant activation of pRB and decreased
      expression of Cyclin D1 in cells treated with the defensin compared to untreated
      control cells, while the expression of p53 remains unaffected. The study of
      intracellular localization of hBD-2 in these cells has revealed that exogeneously
      added defensin molecules enter the cells, are distributed throughout the
      cytoplasm and could be detected in cell nuclei. The model study using A549 cells
      treated with 1,25-(OH)(2)D(3) has shown similar cell growth suppression effect of
      native endogenously produced hBD-2. CONCLUSION: The results of our study suggest
      that in malignant epithelial cells hBD-2 may control cell growth via arrest of
      G1/S transition and activation of pRB.

PMID- 21956462
TI  - Tightly-bound to DNA proteins in rat experimental hepatomas and normal liver
      cells.
AB  - Proteins tightly bound to DNA (TBP) comprise a group of proteins that remain
      bound to DNA even after harsh deproteinization procedures. The amount of these
      proteins is 20-100 MUg for mg of DNA depending on eukaryotic source. This
      experimental paper examines the possibility to use some TBP for clinical
      biomarker discovery, e.g. for identification of prognostic and diagnostic cancer
      markers. The main aim of this study was to designate differences between tightly
      DNA binding protein patterns extracted from rat liver and rat experimental
      hepatomas (Zajdela ascites hepatoma and hepatoma G-27) and to evaluate
      possibility that some of these proteins may be used as biomarkers for cell cancer
      transformation. METHODS: We used proteomics aproach as a tool for comparison of
      pattern of TBP from rat experimental hepatomas and normal liver cells.
      Combination of 2DE fractionation with mass spectrometry (MALDI TOF-MS) suitable
      for parallel profiling of complex TBP mixtures. RESULTS: Intriguingly 2DE protein
      maps of TBP from rat liver and rat experimental hepatomas (Zajdela acites
      hepatoma and hepatoma G-27) were quite different. We identified 9 proteins, some
      of them shared in all TBP patterns. Among identified tightly bound to DNA
      proteins there were three proteins considered as nuclear matrix proteins (lamin
      B1, scaffold attachment factor B1, heterogeneous nuclear ribonucleoprotein). Also
      we identified DNA repair protein RAD50, coiled-coil domain-containing protein 41,
      structural maintenance of chromosomes protein1A and some ATP -dependent RNA
      helicases indicating that TBP are of interest with respect to their potential
      involvement in the topological organization and/ or function of genomic DNA.
      CONCLUSIONS: We suppose that proteomic approach for TBP identification may be
      promising in development of biomarkers, also obtained results may be valuable for
      further understanding TBP functions in genome.

PMID- 21956463
TI  - Effect of vasopressin V1b receptor antagonist, SSR149415, on anxiety-like
      behavior and Lewis lung carcinoma metastasis in mice.
AB  - AIM: To study the effect of new vasopressin V1b receptor antagonist, SSR149415,
      on anxiety-like behavior and Lewis lung carcinoma metastasis in the anxious adult
      male mice of C57Bl/6J strain. This type of receptors was thought to act as
      potential targets mediating the effect of negative psychoemotional state on tumor
      progression. METHODS: Anxiety-like psychoemotional state of the animals was
      produced using chronic social conflict model. Used behavioral tests were elevated
      plus-maze, social interaction test and open field test. Tumor cells were
      administrated on background of double or sixfold SSR149415 injections and the
      number of metastases in the lung were calculated 17 days later. RESULTS:
      SSR149415 reduced the anxiety-like behavior measured in the elevated plus-maze
      and social interaction tests and did not affect locomotor activity in the open
      field test. Double and sixfold administration of the compound to such mice before
      and after inoculation of the tumor cells produced no effect on the metastasis
      rate. CONCLUSION: vasopressin V1b receptor is involved in the mediation of
      anxious behavior of animals but is not involved in the mechanism underlying the
      influence of negative psychoemotional state on Lewis lung carcinoma metastasis.

PMID- 21956464
TI  - Nanohyperthermia of malignant tumors. I. Lanthanum-strontium manganite magnetic
      fluid as potential inducer of tumor hyperthermia.
AB  - OBJECTIVES: To synthesize magnetic particles of lanthanum-strontium manganite,
      prepare the magnetic fluid (MF), evaluate the generation of heat by particles and
      determine their common toxisity. METHODS: Nanoparticles based on the solid
      solutions of lanthanum-strontium manganite (La(1-x)Sr(x)MnO(3)) have been
      synthesized by a sol-gel method. Conventional methods of experimental oncology
      were used. RESULTS: Nanoparticles of ferromagnetic materials on the basis of
      solid solutions of lanthanum strontium manganite by sol-gel method were
      synthesized. It was shown the possibility to regulate the aggregate form of
      particles that are formed during the synthesis. Magnetic fluid based on the
      synthesized nanoparticles and water solutions of agarose have been produced. It
      was shown the possibility to heat this magnetic fluid up to 42-45  degrees S in
      externally applied alternating magnetic field (AMF) operated at 100-400 kHz. It
      was determined that under long-term influence of AMF nanofluid is heated up to
      temperature which is not over that of magnetic phase transition. It was detected
      that magnetic powder as well as fluid have not displayed acute toxicity or side
      effects (intraperitoneal or intratumoral administration) in animals either intact
      or with transplanted tumors. CONCLUSIONS: Possibility of synthesized magnetic
      fluid to generate heat in externally applied AMF as well as lack of side effects
      allow to consider its as a potential mean for tumor hyperthermia (HT).

PMID- 21956465
TI  - Association of polymorphic G1934A variant (allele *4) of CYP2D6 gene with
      increased risk of breast cancer development in Ukrainian women.
AB  - BACKGROUND: Breast cancer (BC) is among the most common oncologic pathology in
      economically developed countries where it afflicts nearly 10% of women.
      Polymorphism of CYP 2D6 gene is shown to be associated with increased risk of
      development of a number of pathologies, in particular cancer. AIM: The work was
      directed on evaluation of the role of polymorphism G1934A (allele *4) of CYP 2D6
      gene in elevated risk of BC development in Ukrainian women. MATERIALS AND
      METHODS: In the study there were enrolled 85 patients (group I) with
      histologically verified BC diagnosis of stages I and II. Clinical-genealogic
      study has been performed by the method of patient survey and following analysis
      of genealogy. Earlier obtained data on the frequency of genotypes and alleles of
      CYP 2D6 gene in 637 Ukrainian people have been used as a control. For
      determination of allele variant *4 (G1934A) of CYP 2D6 gene the method of PCR
      RFLP has been used. RESULTS: An increased risk of BC development in hereditary
      tainted patients with genotype *4*4 of CYP 2D6 gene compared to the control group
      has been revealed. The frequency of *1*4 (IM) genotype has been found to be
      increased in the group of women with a family history of cancer (41.79%).
      Significant difference between the frequency of *1*1 (EM) and *1*4 (IM) genotypes
      in females with PR-positive and PR-negative tumors in the group of hereditary
      tainted patients has been registered. CONCLUSION: In conclusion, our study has
      revealed an increased risk of BC development in hereditary tainted patients
      compared to control group with genotype *4*4 (RM).

PMID- 21956466
TI  - Increase in serum platelet-derived growth factor (PDGF)-BB reflects lymph node
      involvement in esophageal cancer patients independently from platelet count.
AB  - AIM: To evaluate clinical significance and diagnostic utility of increase in
      serum PDGF-BB (sPDGF-BB) in esophageal cancer, which have not been addressed yet
      despite the relevance of PDGF axis in this cancer type. METHODS:
      Immunoenzymatically assessed sPDGFBB was related to clinicopathological features,
      and inflammatory, angiogenic, and lymphangiogenic indices in 84 patients with
      esophageal cancer and 47 controls. Its diagnostic utility was evaluated by
      receiver operating characteristics (ROC) curve analysis. RESULTS: sPDGF-BB was
      significantly higher in esophageal cancer patients than controls (3.76 vs. 2.66
      MUg/l, p = 0.0001) and corresponded with the disease advancement. Of evaluated
      clinicopathological features, lymph node metastases and distant metastases were
      independently associated with an increase in sPDGF-BB; however, only the
      association with lymph node metastases persist adjustment to platelets. In
      univariate analysis, sPDGF positively correlated with platelets (r=0.70, p <
      0.0001), vascular endothelial growth factor (VEGF)-A (r=0.50, p < 0.0001), VEGF-C
      (r=0.57, p < 0.0001), white blood cells (r=0.32, p = 0.004), C-reactive protein
      (r=0.34, p = 0.004), IL-6 (r=0.35, p = 0.003), and IL-8 (r=0.45, p < 0.0001). In
      multivariate analysis, VEGF-C and platelets were independently associated with
      sPDGF-BB explaining 61% in its variability. With >2.845 MUg/l cut-off, over 76%
      of patients had elevated sPDGF-BB. Its accuracy as lymph node metastases marker
      was 75%, sensitivity and specificity corresponding with >3.029 MUg/l cut-off were
      84 and 61%, respectively. CONCLUSIONS: sPDGF-BB owns potential as a possible
      lymph node metastases marker and might be considered as a diagnostic tool in
      preliminary evaluation of esophageal cancer patients identifying those likely to
      be burdened with lymph node metastases, the disease recurrence monitoring, and/or
      preselecting patients for PDGF-directed cancer therapies.

PMID- 21956467
TI  - Drug resistance associated properties of blasts subpopulations with different
      CD34 expression in childhood acute lymphoblastic leukemia (ALL).
AB  - AIM: The objective of this study was to investigate expression of drug resistance
      associated genes in CD34+ and CD34- leukemic subpopulations in childhood acute
      lymphoblastic leukemia (ALL). METHODS: ALL samples with heterogeneous CD34
      expression were separated into CD34-positive and CD34-negative subpopulations and
      mRNA levels of MDR1, LRP, BCRP and BCL-2 genes were compared. RESULTS: BCL-2 gene
      expression levels did not differ significantly between CD34+ vs CD34-
      subpopulations in most analyzed ALL cases. Oppositely, MDR1 gene had >two-fold
      differences in expression levels between subpopulations in the majority of ALL
      cases. In T-lineage ALL CD34- fractions had increased level of BCRP and LRP genes
      in comparison with CD34+ ones whereas in most of B-lineage ALL expression of
      these genes did not differ. CONCLUSION: It was not found the unique pattern of
      resistance related genes expression in CD34+ vs CD34- subpopulations. However, in
      majority of studied pediatric ALL cases with CD34 heterogeneous expression one of
      subpopulations (positive or negative) could have an advantage for survival
      through elevated expression of drug resistance related genes.

PMID- 21956468
TI  - Analysis of p53, p16(INK4a), pRb and Cyclin D1 expression and human
      papillomavirus in primary ovarian serous carcinomas.
AB  - AIM: To evaluate the prognostic relevance of key cell cycle regulatory proteins
      p53, p16(INK4a), pRb and Cyclin D1 expression, the presence of high risk HPVs and
      their association with clinicopathological parameters and the clinical follow up
      in ovarian cancer patients. METHODS: 53 cases of primary ovarian serous
      carcinomas were immunohistochemically examined for the expression of p53,
      p16(INK4a), pRb and Cyclin D1 proteins. Tumor DNA was extracted from paraffin
      blocks and subjected to HPV 16 and 18 testing. The association between HPV 16 and
      18 E6 oncoprotein and cell cycle proteins expression in ovarian carcinomas also
      was evaluated by immunohistochemistry. RESULTS: We demonstrated that a majority
      of moderately and poorly differentiated ovarian carcinomas are characterized by
      strong expression of p53 and p16(INK4a) proteins. In contrast, strong staining
      with cyclin D1 antibody was observed in well differentiated tumors. The
      correlation between strong p53, pRb, Cyclin D1 and clinical stages of disease was
      also observed. We show that patients with high positivity for p53, p16(INK4a) and
      Cyclin D1 had a poor prognosis and reduced overall survival. The presence of HPV
      16/18 DNA was detected in 17% of ovarian carcinomas. The tumor tissues that
      reacted positively to HPV E6 antibody in focal and diffuse manners had also
      significantly low p53 expression profile. CONCLUSION: These findings suggest that
      p53, p16(INK4a) and Cyclin D1 expression and HPV infection may represent a
      promising tool toward the identification of ovarian cancer patients with poorer
      prognosis and shorter survival who might therefore need a more aggressive therapy
      and HPV screening.

PMID- 21956469
TI  - Immunohistochemical analysis of NaPi2b protein (MX35 antigen) expression and
      subcellular localization in human normal and cancer tissues.
AB  - AIM: To study the expression profile of the NaPi2b protein and its localization
      in breast, ovarian and lung cancer cells in relation to normal tissues adjacent
      to tumor. METHODS: Immunohistochemical analysis with monoclonal antibody MX35 was
      applied for investigation of NaPi2b protein expression in breast, lung and
      ovarian carcinomas. Intensity of NaPi2b protein expression was calculated with
      semiquantitative scores. RESULTS: NaPi2b (MX35) protein expression was detected
      in breast, lung and ovarian cancer cells and adjacent normal tissue. We have
      shown that in contrast to ovarian tumors in breast and lung tumors NaPi2b
      expression is down regulated comparing to correspondent normal tissues.
      CONCLUSION: This study provides the data on the pattern of NaPi2b expression and
      cellular localization in breast, lung and ovarian cancers, which might be useful
      for understanding the mechanism of transport and maintenance of inorganic
      phosphate in cancer and normal cells, as well as for developing novel
      immunotherapeutic approaches based on MX35 monoclonal antibody.

PMID- 21956471
TI  - The first Ukrainian-Swedish Workshop "New approaches to diagnostics and treatment
      of cancer".

PMID- 21956470
TI  - Pristine C(60) fullerenes inhibit the rate of tumor growth and metastasis.
AB  - AIM: To estimate the impact of C(60) fullerene aqueous solution (C(60)FAS) on the
      rate of transplanted malignant tumor growth and metastasis. METHODS: Lewis lung
      carcinoma was transplanted into S57Bl/6J male mice. Conventional methods for the
      evaluation of antitumor and antimetastatic effects have been used. RESULTS: The
      C(60)FAS at low single therapeutic dose of 5 mg/kg inhibited the growth of
      transplanted malignant tumor (antitumor effect) and metastasis (antimetastatic
      effect): the maximum therapeutic effect was found to be of 76.5% for the tumor
      growth inhibition; the increase of animal life span by 22% was found; the
      metastasis inhibition index was estimated as 48%. CONCLUSION: It was found that
      water-soluble pristine S(60) fullerenes efficiently inhibit the transplanted
      malignant tumor growth and metastasis.

PMID- 21956472
TI  - Current status and challenges of personalized treatment of cancer: view inspired
      by the workshop.

PMID- 21956473
TI  - Comments on the cross-talk of TGFbeta and EGF in cancer.

PMID- 21956474
TI  - Endometrial cancer and application of proteomics.

PMID- 21956475
TI  - The role of interferon as a modifier of epithelial-mesenchymal transition in
      tumor cells.

PMID- 21956476
TI  - Molecular profile of gastric cancer as a basis of individualized treatment and
      prognosis of disease outcome.

PMID- 21956477
TI  - Additive antitumor effect of plant polyphenols and synthetic inhibitors of
      polyamines biosynthesis.

PMID- 21956478
TI  - The spectrum of blood serum lipids in patients with breast cancer without
      metabolic syndrome.

PMID- 21956479
TI  - Proteomic strategy for detection of circulating tumor cell surface antigens.

PMID- 21956480
TI  - 1,5,2,4,6,8-Dithiatetrazocine. Synthesis, computation, crystallography and
      voltammetry of the parent heterocycle.
AB  - The prototypal 1,5,2,4,6,8-dithiatetrazocine has been synthesized for the first
      time by two routes: reaction of 1,2,3,5-dithiadiazolium chloride with N,N,N'
      tris(trimethylsilyl)formamidine in acetonitrile and reaction of 1,2,3,5
      dithiadiazolyl radical with dioxygen in solution. Yields are low but single
      crystals could be obtained for an X-ray crystal structure determination which
      shows it to have the planar delocalized structure predicted by B3LYP/6
      311+G(2d,p) hybrid DFT calculations. The crystal structure is strongly
      reminiscent of that of benzene in the same Pbca space group. Aromaticity is
      demonstrated by a (1)H NMR chemical shift of +9.70 ppm indicative of diamagnetic
      ring shielding and an intense low-energy optical absorption with lambda(max) =
      349 nm (MeOH). The voltammetric behaviour of the title compound is compared with
      that of 1,3lambda(4)delta(2),5,2,4-trithiadiazepine; both resist electrochemical
      oxidation and reduction over a wide potential range as is typical for aromatic
      heterocycles.

PMID- 21956481
TI  - Natural causes.

PMID- 21956482
TI  - Graphene - a promising material for organic photovoltaic cells.
AB  - As a promising two-dimensional nanomaterial with outstanding electronic, optical,
      thermal, and mechanical properties, graphene has been proposed for many
      applications. In this Progress Report we summarize and discuss comprehensively
      the advances made so far for applications of graphene in organic photovoltaic
      (OPV) cells, including that for transparent electrodes, active layers and
      interfaces layer in OPV. It is concluded that graphene may very likely play a
      major role in new developments/improvements in OPVs. The future studies for this
      area are proposed to focus on the following: i) improving the conductivity
      without comprising the transparency as a transparent electrode material; ii)
      controlling the sheet sizes, band structure and surface morphology for use as a
      electron acceptor material, and iii) controlling and improving the
      functionalization and compatibility with other materials as interface layer
      material.

PMID- 21956483
TI  - Tumour suppressors: Silencing heterochromatin.

PMID- 21956485
TI  - Moving toward "laboratory-supported" criteria for psychogenic tremor.
AB  - A confident clinical diagnosis of psychogenic tremor is often possible, but, in
      some cases, a "laboratory-supported" level of certainty would aid in early
      positive diagnosis. Various electrophysiological tests have been suggested to
      identify patients with psychogenic tremor, but their diagnostic reliability has
      never been assessed "head to head" nor compared to forms of organic tremor other
      than essential tremor or PD. We compared baseline tremor characteristics (e.g.,
      frequency and amplitude) as well as electrophysiological tests previously
      reported to distinguish psychogenic and organic tremor in a cohort of 13 patients
      with psychogenic tremor and 25 patients with organic tremor, the latter including
      PD, essential-, dystonic-, and neuropathic tremors. We assessed between-group
      differences and calculated sensitivity and specificity for each test. A number of
      tests, including entrainment or frequency changes with tapping, pause of tremor
      during contralateral ballistic movements, increase in tremor amplitude with
      loading, presence of coherence, and tonic coactivation at tremor onset, revealed
      significant differences on a group level, but there was no single test with
      adequate sensitivity and specificity for separating the groups (33%-77% and 84%
      100%, respectively). However, a combination of electrophysiological tests was
      able to distinguish psychogenic and organic tremor with excellent sensitivity and
      specificity. A laboratory-supported level of diagnostic certainty in psychogenic
      tremor is likely to require a battery of electrophysiological tests to provide
      sufficient specificity and sensitivity. Our data suggest such a battery that, if
      supported in a prospective study, may form the basis of laboratory-supported
      criteria for the diagnosis of psychogenic tremor.

PMID- 21956487
TI  - Vibration training and body fat: a comment on Artero et al. (2011).

PMID- 21956486
TI  - Short-term street soccer improves fitness and cardiovascular health status of
      homeless men.
AB  - This study examined the effect of 12 weeks of small-sided street soccer (2.2 +/-
      0.7 sessions/week) and fitness center training (0.5 +/- 0.2 sessions/week) on
      physical fitness and cardiovascular health profile for homeless men. Exercise
      capacity, maximal oxygen uptake (VO(2max)), body composition (DXA scans), blood
      pressure (BP), and blood lipid profile were determined before and after the
      intervention period for 22 soccer-group subjects (SG) and 10 waiting list
      controls (CO). In addition, time-motion analyses, HR measurements, and pedometer
      recordings were performed during street soccer training and daily-life
      activities. During a 60 min 4 versus 4 street soccer session 182 +/- 62 intense
      running bouts were performed; mean HR was 82 +/- 4% HR(max) and HR was >90%
      HR(max) for 21 +/- 12% (+/-SD) of total time. On a day without training the
      participants performed 10,733 +/- 4,341 steps and HR was >80% HR(max) for 2.4 +/-
      4.3 min. In SG, VO(2max) was elevated (p < 0.05) from 36.7 +/- 7.6 to 40.6 +/-
      8.6 ml/min/kg after 12 weeks and incremental cycle test performance was improved
      (p < 0.05) by 81 s (95% CI: 47-128 s). After 12 weeks, fat percentage (19.4 +/-
      8.5 to 17.5 +/- 8.6%) and LDL cholesterol (3.2 +/- 1.1 to 2.8 +/- 0.8 mmol L(-1))
      were lowered (p < 0.05) in SG. The observed changes in SG were different (p <
      0.05) from CO and no intra-group changes occurred for CO (p > 0.05). BP was
      unaltered after 12 weeks (p > 0.05), but diastolic BP was lowered for all SG
      subjects with pre-values >75 mmHg (83 +/- 6 to 76 +/- 6 mmHg, n = 8, p < 0.05).
      In conclusion, the exercise intensity is high during street soccer and regular
      street soccer training can be used as an effective activity to promote physical
      fitness and cardiovascular health status for homeless men.

PMID- 21956488
TI  - Tc-99m sestamibi scintimammography for the diagnosis of breast cancer:  meta
      analysis and meta-regression.
AB  - Tc-99m sestamibi (MIBI) is a relatively noninvasive diagnostic modality in the
      evaluation of breast cancer. The purpose of this study was to review the existing
      literature on the accuracy of Tc-99m MIBI in the diagnosis of breast cancer.
      After a systematic review of English-language studies, the sensitivity,
      specificity, and other measures of accuracy of Tc-99m MIBI in the diagnosis of
      breast cancer were pooled using random-effects models. Summary receiver operating
      characteristic curves were used to summarize the overall test performance. Forty
      five studies met our inclusion criteria. The summary estimates for Tc-99m MIBI in
      the diagnosis of breast cancer in the studies included were as follows:
      sensitivity, 0.83 [95% confidence interval (CI), 0.82-0.84]; specificity, 0.85
      (95% CI, 0.83-0.86); positive likelihood ratio, 5.06 (95% CI, 4.26-6.01);
      negative likelihood ratio, 0.20 (95% CI, 0.17-0.24); and diagnostic odds ratio,
      27.63 (95% CI, 21.63-36.10). For patients with a palpable mass, the sensitivity
      and specificity were 87 and 86%, respectively. For patients without a palpable
      mass, the sensitivity and specificity were 59 and 89%, respectively. Tc-99m MIBI
      has a high level of overall accuracy for the diagnosis of breast cancer.

PMID- 21956489
TI  - The clinical value of fluorine-18 fluorodeoxyglucose positron emission
      tomography/computed tomography in postoperative patients with gastrointestinal
      mucinous adenocarcinoma.
AB  - OBJECTIVE: To evaluate the clinical value of F-fluorodeoxyglucose positron
      emission tomography and computed tomography (18F-FDG PET/CT) in postoperative
      patients with gastrointestinal mucinous adenocarcinoma. METHODS: From July 2007
      to March 2009, 30 patients who had previous surgical resection of
      histopathologically diagnosed gastrointestinal mucinous adenocarcinoma underwent
      18F-FDG PET/CT scans in our center. The standard of reference for tumor
      recurrence, regional lymph node (LN) metastasis, peritoneal and distant
      metastasis consisted of histopathologic confirmation or clinical follow-up
      information for at least 6 months after PET/CT examinations. RESULTS: With final
      diagnosis, tumor recurrences were confirmed in eight of the 30 patients (26.7%).
      If a maximum standardized uptake value (SUVmax) of 2.5 or more was used as a cut
      off point, the sensitivity, specificity, and accuracy of PET/CT were 87.5, 77.3,
      and 80.0%, respectively. However, if an SUVmax of 4.0 or more was the criterion,
      the sensitivity, specificity, and accuracy were 25.0, 86.4, and 70.0%,
      respectively. A cut-off point of 2.5 showed a higher sensitivity (P=0.041), and
      there was no statistical difference in the specificity and the accuracy of these
      two criteria. For the diagnosis of metastasis in regional LNs and peritoneum, the
      detection rate was 95.2 and 86.4%, respectively. In addition, we followed up 20
      patients with 26 suspicious distant lesions. The sensitivity, specificity, and
      accuracy were 58.3, 92.9, and 76.9%, respectively. CONCLUSION: 18F-FDG PET/CT may
      be effective to discriminate tumor recurrence, and to detect regional LNs,
      peritoneal and distant metastasis in postoperative patients with gastrointestinal
      mucinous adenocarcinoma.

PMID- 21956490
TI  - Half-time myocardial perfusion SPECT imaging with attenuation and Monte Carlo
      based scatter correction.
AB  - PURPOSE: To test the potential of a new reconstruction algorithm with Monte Carlo
      based scatter correction in half-time myocardial perfusion single-photon emission
      computed tomography (SPECT). MATERIALS AND METHODS: The mathematical four
      dimensional NURBS-based Cardiac-Torso phantom and the SIMIND Monte Carlo
      simulation package were used to simulate full-time and half-time SPECT projection
      data. The data were reconstructed using the standard ordered subset expectation
      maximization-based algorithm and the new Monte Carlo-based algorithm. Defect
      contrast, myocardium versus ventricle contrast and resolution were calculated. In
      addition to the simulation studies, full-time and half-time SPECT projection data
      of 30 patients were reconstructed with the standard and the new method. The
      patient data were qualitatively evaluated by four nuclear medicine experts on a
      scale from 1 (poor quality) to 5 (high quality). RESULTS: The new reconstruction
      method with half-time data produced higher contrast and better resolution in the
      simulations and also achieved higher qualitative scores in the patient study than
      the standard reconstruction with full-time data. CONCLUSION: Half-time myocardial
      perfusion imaging using the new reconstruction algorithm with Monte Carlo-based
      scatter correction produced images with superior quality when compared with full
      time imaging with standard reconstruction.

PMID- 21956491
TI  - Poly(ADP-ribose) polymerase inhibitors combined with external beam and
      radioimmunotherapy to treat aggressive lymphoma.
AB  - PURPOSE: To assess the possible radiosensitizing capabilities of two different
      poly(ADP-ribose) polymerase (PARP) inhibitors in combination with external beam
      and I-tositumomab in a non-Hodgkin's lymphoma cell line. METHODS AND MATERIALS:
      Epstein-Barr virus-infected human Raji lymphoma cells with lentivirally
      transfected green fluorescent protein and luciferase in log-phase growth were
      incubated with various doses of AZD-2281 and ABT-888 24 h before external beam
      radiation exposure. A 500 nmol/l concentration of AZD-2281 and ABT-888 was used
      to assess the growth curve of Raji lymphoma cells over 5 days. The number of
      double-stranded breaks was visually assessed using a H2AX antibody and confocal
      microscopy. Intracellular PARP activity was measured 2 h after incubation with
      AZD-2281 (500 nmol/l) and ABT-888 using a colorimetric PARP assay kit. The
      radiosensitizing effect of AZD-2281 (500 nmol/l) with various doses of I
      tositumomab was assessed after 24 h. RESULTS: A volume of 500 nmol/l of AZD-2281
      and 500 nmol/l of ABT-888, in combination with 0, 4, 8, and 12 Gy external beam
      radiation, showed a 5.2, 7.1, 10.1, and 33.1% radiosensitization. A measure of
      500 nmol/l AZD-2281 and ABT-888 significantly reduced the percentage of viable
      cells on days 3-5 compared with controls. The maximal relative reduction in
      viable cells was 78.5%, and this occurred with AZD-2281 (500 nmol/l) on day 5.
      AZD-2281 revealed a higher number of double-stranded breaks with confocal
      microscopy than did ABT-888. Two hours after incubation of Raji cells with 500
      nmol/l of AZD-2281 or ABT-888, the colorimetric PARP activity assay showed a
      reduction of 30.36% with ABT-888 and of 47.8% with AZD-2281. Combining AZD-2281
      (500 nmol/l) with 0, 5 MUCi (0.185 MBq), 10 MUCi (0.37 MBq) and 20 MUCi (0.74
      MBq) 131I-tositumomab revealed a significant reduction in cell viability after 24
      h with 5 MUCi (0.185 MBq) (P<0.01) and 10 MUCi (0.37 MBq) (P<0.01) radiation
      dose. CONCLUSION: PARP inhibitors AZD-2281 and ABT-888 are highly
      radiosensitizing agents when used before external beam radiation and 131I
      tositumomab.

PMID- 21956492
TI  - Computerized scar detection on renal cortical scintigraphy images.
AB  - OBJECTIVE: Renal cortical scintigraphy is a well-established functional imaging
      technique for visual analysis of radiopharmaceutical tracer distribution.
      However, the visual evaluation is subjective, causing interobserver variability,
      especially in a quantifiable number of scars. The purpose of this study was to
      develop new computerized methods in renal cortical scintigraphy image
      interpretation, particularly addressing activity distribution and cortex
      continuity (scars). METHODS: The proposed methods involve preprocessing stages of
      model-based automatic kidney segmentation using active-shape model and image
      normalization (transforming each kidney image into a standardized image vector).
      For our previous computer-aided diagnosis scheme, two new image-based features
      [localized activity drop and principal component analysis (PCA)] were defined.
      Their performance was evaluated and compared with our previous scheme by using
      free-response receiver operating characteristic that is in terms of sensitivity
      (true-positive fraction) and the mean number of false positives (FPs) per image.
      RESULTS: Clinical tests were conducted in 297 patients (231 normal and 66
      abnormal). The PCA-based image feature presented the best scar detection
      performance, followed by the localized activity drop feature. Both schemes were
      found to be superior to our previous computer-aided diagnosis scheme. In the PCA
      based scheme, for sensitivity of 0.90 (76/84), the mean number of FPs was
      measured as 4.52 (1343/297). For another setting with reduced sensitivity of 0.79
      (66/84), the mean number of FPs improved to 1.21 (360/297). Finally, a decision
      fusion scheme using 'majority voting' was also proposed, the sensitivity and mean
      number of FPs of which were measured as 0.83 (70/84) and 1.90 (563/297),
      respectively. CONCLUSION: The proposed methods have potential to provide
      effective second-reader information to nuclear medicine specialists in finding
      scar regions. Possible ways to improve the FP rate were also proposed.

PMID- 21956494
TI  - Nucleolin antisense oligodeoxynucleotides induce apoptosis and may be used as a
      potential drug for nasopharyngeal carcinoma therapy.
AB  - Nucleolin (C23, NCL) mRNA was up-regulated in nasopharyngeal carcinoma (NPC)
      cells compared to that of normal nasomucosal (NNM) cells using a cDNA microarray
      approach. The level of nucleolin protein was also up-regulated in 13 NPC cell
      lines, 30 biopsy specimens and nine other cancer cell lines compared to five NNM
      cells or normal stromal cells, which were analyzed using immunoblotting or
      immunohistochemistry. We transfected nucleolin antisense oligodeoxynucleotides
      (phosphorothioate-modified oligodeoxynucleotides; S-ODNs) into NPC-TW01 cells to
      knockdown nucleolin expression to evaluate the function of nucleolin in cancer
      cells. Nucleolin knockdown induced NPC cells but not NNM cells to undergo
      apoptosis. Furthermore, treatment of NPC-TW01 xenograft tumors with nucleolin
      antisense oligodeoxynucleotides suppressed the growth of xenograft tumors without
      obvious side effects. Therefore, we suggest that nucleolin may be a potential
      cancer therapeutic target and that nucleolin antisense oligodeoxynucleotides may
      be used as a potential drug for therapy in NPC.

PMID- 21956495
TI  - Cause of death in neonates with inconclusive or abnormal T-cell receptor excision
      circle assays on newborn screening.
AB  - INTRODUCTION: During the first 2 years of newborn screening (NBS) for severe
      combined immunodeficiency (SCID), 39 infants with an abnormal or inconclusive
      newborn screening test for SCID died prior to assessment of immune function. We
      investigated if SCID or primary T-cell lymphopenia likely contributed to the
      death of these neonates. METHODS: This study is a detailed retrospective chart
      review. RESULTS: Medical records were available in all 39 infants. Three neonates
      were full-term infants whose deaths were due to congenital anomalies. Thirty
      three infants were born <33 weeks estimated gestational age, and the majority of
      these infants died from complications of prematurity. Six infants died from
      sepsis: two due to maternal chorioamnionitis, two due to necrotizing
      enterocolitis, one due to early onset group B strep sepsis, and one from a likely
      nosocomial infection. CONCLUSIONS: There was no evidence that SCID contributed to
      the cause of death in neonates with an abnormal of inconclusive NBS test for
      SCID.

PMID- 21956496
TI  - Nationwide survey of patients with primary immunodeficiency diseases in Japan.
AB  - To determine the prevalence and clinical characteristics of patients with in
      Japan, we conducted a nationwide survey of primary immunodeficiency disease (PID)
      patients for the first time in 30 years. Questionnaires were sent to 1,224
      pediatric departments and 1,670 internal medicine departments of Japanese
      hospitals. A total of 1,240 patients were registered. The estimated number of
      patients with PID was 2,900 with a prevalence of 2.3 per 100,000 people and
      homogenous regional distribution in Japan. The male-to-female ratio was 2.3:1
      with a median age of 12.8 years. Adolescents or adults constituted 42.8% of the
      patients. A number of 25 (2.7%) and 78 (8.5%) patients developed malignant
      disorders and immune-related diseases, respectively, as complications of primary
      immunodeficiency disease. Close monitoring and appropriate management for these
      complications in addition to prevention of infectious diseases is important for
      improving the quality of life of PID patients.

PMID- 21956497
TI  - Unique strengths of ELISPOT for T cell diagnostics.
AB  - The T cell system plays an essential role in infections, allergic reactions,
      tumor and transplant rejection, as well as autoimmune diseases. It does so by the
      selective engagement of different antigen-specific effector cell lineages that
      differentially secrete cytokines and other effector molecules. These T cell
      subsets may or may not have cytolytic activity, can preferentially migrate to
      different tissues, and display variable capabilities to expand clonally. The
      quest of T cell immune diagnostics is to understand which specific effector
      function and T cell lineage is associated with a given clinical outcome, be it
      positive or adverse. No single assay can measure all of the relevant parameters.
      In this chapter, we review the unique contributions that ELISPOT assays can make
      toward understanding T cell-mediated immunity. ELISPOT assays have an unsurpassed
      sensitivity in detecting low frequency antigen-specific T cells that secrete
      effector molecules, including granzyme and perforin. They provide robust, highly
      reproducible data - even by first time users. Because ELISPOT assays require
      roughly tenfold less cell material than flow cytometry, ELISPOT is ideally suited
      for all measurements requiring parallel testing under multiple conditions. These
      include defining (a) T cell reactivity to individual peptides of extensive
      libraries, thereby establishing the fine-specificity of the response, and
      determinant mapping; (b) reactivity to different concentrations of the antigen in
      serial dilutions to measure the avidity of the T cell response; or (c) different
      secretory products released by T cells which define their respective effector
      lineage/functions. Further, because T cells survive ELISPOT assays unaffected,
      they can be retested for the acquisition of additional information in follow-up
      assays. These strengths of ELISPOT assays the weaknesses of flow cytometry-based
      measurements. Thus, the two assays systems compliment each other in the quest to
      understand T cell-mediated immunity in vivo.

PMID- 21956498
TI  - The impact of harmonization on ELISPOT assay performance.
AB  - During more than 25 years of application in immunological sciences, ELISPOT has
      been established as a routine, robust, versatile, and reliable assay. From basic
      research to clinical immune monitoring, ELISPOT is being used to address the
      quantification and (to a lesser extent) functional characterization of immune
      cells secreting different molecules in the context of health and disease, immune
      intervention, and therapy in humans and other species [Kalyuzhny (Ed.) (2005)
      Handbook of Elispot: methods and protocols, Vol. 302, Humana Press Inc., Totowa,
      NJ]. Over the last decade, ELISPOT assays have been increasingly implemented as
      an immune-monitoring tool in clinical trials [Schmittel et al. J Immunother
      23:289-295, 2000; Whiteside Immunol Invest 29:149-162, 2000; Nagata et al. Ann N
      Y Acad Sci 1037:10-15, 2004; Cox et al. (2005) Cellular immune assays for
      evaluation of vaccine efficacy in developing countries., In Manual of Clinical
      Immunology Laboratory (Rose, N. R., Hamilton, R. G., and Detrick, B., Eds.), p
      301, ASM Press, Washington, DC; Cox et al. Methods 38:274-282, 2006]. While the
      principles of the original protocol have changed little since its first
      introduction [Czerkinsky J Immunol Methods 110:29-36, 1988], individual
      laboratories have adapted assay procedures based on experimental needs,
      availability of reagents and equipment, obtained recommendations, and gained
      experience, leading to a wide disparity of applied ELISPOT protocols with
      inevitable consequences. This chapter addresses the resulting challenges for
      ELISPOT use in clinical trial settings, and discusses the influence of
      harmonization strategies as a tool for overcoming these challenges. Furthermore,
      harmonization is discussed in the context of assay standardization and validation
      strategies.

PMID- 21956499
TI  - Equine ELISPOT assay to study secretion of IFNgamma and IL-4 from peripheral
      blood mononuclear cells.
AB  - Human and mouse immune system cells are the most frequently used specimens in
      ELISPOT assays. In an effect to expand the application of ELISPOT assay to other
      species, we developed matched antibody pairs for ready-to-use kits designed for
      studying the frequency of equine IFNgamma- and IL-4-secreting peripheral blood
      mononuclear cells (PBMCs). Equine PBMCs were stimulated with either concanavalin
      A (Con A) or calcium ionomycin mixed with phorbol 12-myristate 13-acetate (CaI +
      PMA). We found that Con A, in general, had a more profound stimulating effect
      than CaI + PMA on IL-4 secretion, whereas both stimulatory and inhibitory effects
      were observed on IFNgamma secretion. Our data demonstrate a large dynamic range
      in IFNgamma and IL-4 secretion among different donors, which may reflect animal
      health and serve as a valuable diagnostic marker.

PMID- 21956500
TI  - Utilization of feline ELISPOT for mapping vaccine epitopes.
AB  - A commercial feline immunodeficiency virus (FIV) vaccine consisting of
      inactivated dual-subtype viruses was released in the USA in 2002 and released
      subsequently over the next 6 years in Canada, Australia, New Zealand, and Japan.
      Based on the genetic, morphologic, and biochemical similarities between FIV and
      human immunodeficiency virus-1 (HIV-1), FIV infection of domestic cats is being
      used as a small animal model of HIV/AIDS vaccine. Studies on prototype and
      commercial FIV vaccines provide new insights to the types of immunity and the
      vaccine epitopes required for an effective human HIV-1 vaccine. ELISPOT assays to
      detect cytokines, chemokines, and cytolytic mediators are widely used to measure
      the magnitude and the types of cellular immunity produced by vaccination.
      Moreover, such approach has identified regions on both HIV-1 and FIV proteins
      that induce robust antiviral cellular immunity in infected hosts. Using the same
      strategy, cats immunized with prototype and commercial FIV vaccines are being
      analyzed by feline interferon-gamma and IL-2 ELISPOT systems to identify the
      vaccine epitope repertoire for prophylaxis.

PMID- 21956501
TI  - Analyzing cellular immunity to AAV in a canine model using ELISPOT assay.
AB  - Adeno-associated viral (AAV) vector-mediated gene transfer represents a promising
      gene replacement strategy for treating various genetic diseases. One obstacle in
      using viral-derived vectors for in vivo gene delivery is the development of host
      immune responses to the vector. Recent studies have demonstrated cellular immune
      responses specific to capsid proteins of various AAV serotypes in animal models
      and in human trials for different diseases. We developed a canine-specific
      ELISPOT assay to detect such immunity in dogs received AAV treatment. Here, we
      describe in detail the use of a constructed panel of overlapping peptides
      spanning the entire VP1 sequence of AAV capsid protein to detect specific T-cell
      responses in peripheral blood in dogs following intramuscular injection of AAV.
      This high-throughput method allows the identification of T-cell epitopes without
      the need for large cell numbers and the need for major histocompatibility complex
      molecule-matched cell lines.

PMID- 21956502
TI  - Dual- and triple-color fluorospot.
AB  - Cytokine ELISPOT has become a powerful routine tool for the analysis of disease-
      as well as vaccine-induced T-cell responses. The method is limited, however, in
      that only one cytokine at a time is assessed. Fluorospot is based on the
      principle of ELISPOT, but facilitates the analysis of single cells secreting
      several cytokines, e.g., polyfunctional T cells, suggested to be of protective
      importance in various infectious diseases. By detecting each cytokine with a
      specific fluorophore and analyzing differentially colored spots by fluorophore-
      specific filter systems, cells producing single or multiple cytokines are
      identified. Fluorospot maintains the simplicity and sensitivity of the ELISPOT
      while taking the analysis a step forward toward multiplex analysis.

PMID- 21956503
TI  - ELISPOT assay as a tool to study oxidative stress in lymphocytes.
AB  - Enzyme-linked immuno spot (ELISPOT) assay is widely used for vaccine development,
      cancer and AIDS research, and autoimmune disease studies. The output of ELISPOT
      assay is a formation of colored spots which appear at the sites of cells
      releasing cytokines, with each individual spot representing a single cytokine
      releasing cell. We worked out a protocol to study oxidative stress in human
      peripheral blood lymphocytes by determining their potency to secrete IFN-gamma,
      IL-2, IL-4, IL-5, IL-8, and TNF-alpha in response to acute treatment with
      hydrogen peroxide. We show that hydrogen peroxide-induced oxidative stress can
      cause a ~twofold decrease in the number of lymphocytes secreting the TH1
      cytokines IFN-gamma and IL-2, as well as chemokines IL-8 and TNF-alpha. However,
      the number of cells secreting TH2 cytokines IL-4 and IL-5 in hydrogen -peroxide
      treated group did not change. It appears that oxidative stress may affect TH1-TH2
      cytokine secretion -balance which, in turn, may underlie developments of various
      pathological conditions. This protocol can be easily modified to study the
      effects of many other oxidative stress compounds.

PMID- 21956504
TI  - ELISPOT assay for neuroscience research: studying TNFalpha secretion from
      microglial cells.
AB  - The major application of ELISPOT assays is to study secretion of cytokines and
      chemokines from immune system cells. We adapted this assay to study TNFalpha
      secretion from microglial BV2 cells, which are similar in physiology to microglia
      in the nervous system. Stimulation of BV2 cells with 1 MUg/mL LPS resulted in a
      robust secretion of TNFalpha. Unlike uniform round spots formed by TNFalpha
      secreted by immune system cells, BV2 cells produced spots with short zigzag
      "tails" indicating that BV2 cells were actively moving during the incubation. In
      spite of irregular shapes, spots could be easily counted using an ELISPOT reader.
      Our study has shown the feasibility of employing an ELISPOT assay as a tool for
      neuroscience research to study the mechanisms underlying protein secretion from
      microglial cells. In addition, due to its convenient format, ELISPOT can be used
      for high-throughput screening of the potency of novel drugs to stimulate or
      inhibit cytokine secretion by microglial cells in the brain.

PMID- 21956505
TI  - ELISPOT assay as a tool to study the effects of stem cells on cytokine secretion.
AB  - Mesenchymal stem cells (MSCs) have many regulatory effects (e.g., T-cell
      suppression) on various immune cells. As aberrant T-cell activation is a primary
      cause of many diseases, understanding the underlying mechanisms of how MSCs exert
      immunosuppression is an important issue with potential therapeutic implications.
      A group of cytokines was shown to be involved as soluble mediators in the
      immunosuppressive effects of MSCs. An enzyme-linked immunospot (ELISPOT) assay is
      an ideal method to find potential mediators involved in the MSC
      immunosupporessive pathway; additionally, the ELISPOT assay can measure changes
      in the full spectrum of cytokines produced during T-cell activation in the
      presence of MSCs. Here, we show that during a mixed lymphocyte reaction,
      interleukin-10 (IL-10)-secreting splenocytes increased in number in the presence
      of MSC-conditioned media; the increase in IL-10 levels in the supernatant was
      confirmed by an independent enzyme-linked immunosorbent assay (ELISA).

PMID- 21956506
TI  - Combining ELISPOT and ELISA to measure amounts of cytokines secreted by a single
      cell.
AB  - Enzyme-linked immunospot (ELISPOT) assay allows for the determination of the
      frequency of -cytokine-secreting cells, but does not answer the question of how
      much cytokine is secreted per cell. In our study, we combined ELISPOT and ELISA
      assays and developed a protocol to calculate the amount of IFN gamma secreted by
      each cell. A suspension of human peripheral blood mononuclear cells was split
      into two pools and cells from one pool were cultured in a regular ELISPOT plate,
      whereas cells from the other pool were cultured in an uncoated, "blank," ELISPOT
      plate. After finishing the incubations, the amount of IFN gamma was measured by
      ELISA in culture media collected from both plates. The "blank" plate served to
      measure a total amount of secreted IFN gamma, whereas the ELISPOT plate served to
      measure the amount of unbound (UB) IFN gamma. Subtracting the amount of unbound
      IFN gamma from its total amount and dividing it by the number of spots in the
      ELISPOT plate allows for the calculation of the average amount of IFN gamma in a
      spot formed by a single cell.

PMID- 21956507
TI  - How ELISPOT morphology reflects on the productivity and kinetics of cells'
      secretory activity.
AB  - Over the past decade, ELISPOT has become well-established as a mainstream
      technology for the study of immune responses in vivo mainly due to its unique
      ability to detect rare antigen-specific lymphocytes ex vivo. The primary readout
      for ELISPOT assays has traditionally been the measurement of the frequency of
      analyte-secreting cells within a test population. While it has been generally
      appreciated that ELISPOT is a high-information-content assay system in which spot
      morphologies provide additional valuable information on the amount of analyte
      secreted by individual cells as well as the kinetics of the secretory process,
      the precise relationships involved have not been fully characterized and the
      specific relevant information -conveyed by spot morphologies has remained largely
      unexplored. In an attempt to bridge this gap, we formulated an in silico kinetic
      model for spot formation and derived a solution for the model in both a general
      and a numerical form. Both solutions suggested a logarithmic relationship between
      spot size and cell productivity. This chapter involves an in-depth analysis of
      the relationship between observed spot morphologies and cells' secretory
      functions (as well as an examination of additional assay parameters), and
      predictions based on the mathematical model are verified under experimental assay
      conditions where possible.

PMID- 21956508
TI  - Mathematical algorithms for automatic search, recognition, and detection of spots
      in ELISPOT assay.
AB  - Accuracy of spot detection and quantification plays a critical role in the
      analysis of ELISPOT data. Differences in staining intensities of spots and their
      morphological variations make it difficult developing a reliable software
      application. We have developed an image recognition method allowing for the
      automatic detection of round objects (spots) on ELISPOT images independently of
      the registration conditions. The emphasis is done on objects of elliptical shape
      which is typical for a wide range of spots that can be analyzed by both
      monochrome and a dual-color version of our software. The method of subdivision of
      objects into groups is also described which is based on color attributes of
      spots.

PMID- 21956509
TI  - Objective, user-independent ELISPOT data analysis based on scientifically
      validated principles.
AB  - ELISPOT results used to be evaluated visually which, however, is inevitably
      subjective, inaccurate, and cumbersome. Even when applying automated image
      analysis to this end, the results are highly variable if the counting parameters
      are set subjectively. Since objective, accurate, and reproducible measurements
      are fundamental to science, major efforts have been undertaken over the last
      decade at CTL to understand the scientific principles behind ELISPOT data and to
      develop "intelligent" image analysis algorithms based on these principles. Thus,
      a spot recognition and gating algorithm was developed to automatically recognize
      the signatures of defined cell populations, such as T cells, discerning them from
      irrelevant cell types and noise. In this way, the science of ELISPOT data
      analysis has been introduced, permitting exact frequency measurement against
      background. As ELISPOT assays become a gold standard for monitoring antigen
      specific T-cell immunity in clinical trials, the need has surfaced to make
      ELISPOT data transparent, reproducible, and tamper-proof, complying with Good
      Laboratory Practice (GLP) and Code for Federal Regulations (CFR) Part 11
      guidelines. Flow cytometry-based and other immune monitoring assay platforms face
      the same challenge. In this chapter, we provide an overview of how CTL's
      ImmunoSpot((r)) platform for ELISPOT data analysis, management, and documentation
      meets these challenges.

PMID- 21956510
TI  - Statistical analysis of ELISPOT assays.
AB  - Cytokine ELISPOT assays have emerged as a powerful tool for the detection of rare
      antigen-specific T cells in freshly isolated cell material, such as blood. While
      ELISPOT assays allow one to directly visualize and count extremely low
      frequencies of cytokine-secreting T cells among millions of nonsecreting
      bystander cells, the interpretation of ELISPOT data can become ambiguous when (a)
      spot numbers in antigen-containing wells are low, (b) spot counts in negative
      control wells are elevated, and particularly (c) when both of the above occur
      simultaneously. Thus, the primary task, even before statistics are employed, must
      be the optimization of the basic assay parameters and reagents such that the
      assay yields low background signal in the negative-control wells and the maximal
      number of antigen-induced spots in test wells, i.e., the signal-to-noise ratio is
      maximized. Furthermore, the use of proper spot-size gating parameters for data
      analysis is indispensable for screening out irrelevant background spots, and thus
      increasing the signal-to-noise ratio. The goal of most ELISPOT experiments is to
      identify positive T-cell responses as defined by a significantly elevated spot
      count in antigen-stimulated wells over the nonstimulated medium-control or
      negative-control antigen. In this chapter, we conclude that - with some
      limitations - the T-Test and related statistical methods which rely on the
      assumption of normal distribution are suitable for identifying positive ELISPOT
      results.

PMID- 21956511
TI  - Response determination criteria for ELISPOT: toward a standard that can be
      applied across laboratories.
AB  - ELISPOT assay readout is often dichomized as positive or negative responses
      according to prespecified criteria. However, these criteria can vary widely
      across institutions. The adoption of a common response criterion is a key step
      toward cross-laboratory comparability. This chapter describes the two main
      approaches to response determination, identifying the strengths and limitations
      of each. Nonparametric statistical tests and consideration of data quality are
      recommended and instructions provided for their ready implementation by
      nonstatisticians and statisticians alike.

PMID- 21956512
TI  - Detection of vaccinia virus-specific IFNgamma and IL-10 secretion from human
      PBMCs and CD8+ T cells by ELISPOT.
AB  - High-throughput in vitro assays, which rapidly and succinctly assess the immune
      status of large cohorts of individuals, are essential tools for conducting
      population-based studies, including vaccine research. The enzyme-linked
      immunospot (ELISPOT) assay has emerged as a sensitive, reliable high-throughput
      tool to measure functional recall immunity by assessing the frequency of antigen
      specific cytokine-secreting lymphocytes present in peripheral blood mononuclear
      cells (PBMCs). For the past 10 years, ELISPOT method has been the dominant
      platform and a standard for the cell-mediated immune (CMI) assays. ELISPOT assays
      are used extensively as a measure of CMI response to vaccines, including smallpox
      (vaccinia), following primary or secondary vaccination. Here, we present detailed
      methodology for using ELISPOT assays to detect the frequency of cytokine
      secreting vaccinia-specific lymphocytes including optimized protocols for
      growing, titrating, and inactivating vaccinia virus; isolating, cryopreserving,
      and thawing human PBMCs; and finally, detecting vaccinia-specific IL-10 and
      IFNgamma secreting lymphocytes, as well as CD8(+) IFNgamma T cells following in
      vitro stimulation of PBMCs with vaccinia virus. The methods presented below,
      although optimized for vaccinia virus, emphasize principles that can be generally
      applied to create ELISPOT assays capable of assessing the immune status as well
      as antiviral CD8(+) T cell response of individuals following primary or secondary
      vaccination with other licensed or novel vaccines.

PMID- 21956513
TI  - ELISPOT assays to enumerate bovine IFN-gamma-secreting cells for the development
      of novel vaccines against bovine tuberculosis.
AB  - Enumeration of antigen-specific cells after vaccination is one of the prime
      immunological parameters determined when developing vaccines. Due to their
      exquisite sensitivity (limits of detection can be below 1/100,000 cells), ELISPOT
      assays are therefore an important tool in vaccine development programs. This is
      particularly the case for vaccines against diseases that require protective cell
      mediated immunity, such as tuberculosis. This chapter describes ELISPOT assays
      detecting bovine IFN-gamma.

PMID- 21956514
TI  - IL-7 addition increases spot size and number as measured by T-SPOT.TB ((r)).
AB  - The interferon-gamma (IFN-gamma) release assay (IGRA) is an in vitro extension of
      the century-old in vivo tuberculin skin test, better known as the TST.
      Shortcomings to the TST are multifactorial and include limitations in sensitivity
      and specificity. IGRAs improve diagnostic specificity by using antigens not found
      in the Bacille Calmette-Guerin, a vaccine given in most countries. IGRAs capture
      the IFN-gamma produced by T cells in response to antigen stimulation. The ELISPOT
      immediately captures IFN-gamma produced directly from each cell, resulting in the
      generation of a cellular "footprint." The dimensions and intensity of the
      generated footprint indicate the avidity of the secreting cell. We show a further
      improvement in IGRAs by addition of interleukin-7 (IL-7). IL-7 reduces T-cell
      apoptosis and stabilizes IFN-gamma message. In addition to increasing the number
      of spots in the ELISPOT T-SPOT.TB platform, IL-7 increased IFN-gamma production
      per cell as measured by an increase in spot size with no change in spot
      distribution.

PMID- 21956515
TI  - Overview of membranes and membrane plates used in research and diagnostic ELISPOT
      assays.
AB  - Polyvinylidene fluoride (PVDF) membrane-bottomed, 96-well plates and 8-well
      strips constitute the formats in which the overwhelming majority of ELISPOT
      assays used in research and diagnostic applications are performed. PVDF is well
      suited for ELISPOT because it has a high antibody-binding capacity and because
      its white color provides an excellent backdrop for ELISPOT enumeration.
      Nitrocellulose (NC) and PVDF membranes and 96-well plates containing those
      membranes used in ELISPOT assays were initially commercialized for filtration
      applications and later optimized for a range of different protein analytical
      applications. An overview of the development and biotechnology applications of
      PVDF membrane is provided. Characteristics and attributes of the membrane that
      are relevant to ELISPOT are summarized. Enhancements in PVDF membrane performance
      and optimization of devices for automation compatible and diagnostic ELISPOT
      applications are presented.

PMID- 21956516
TI  - Route to a family of robust, non-interpenetrated metal-organic frameworks with
      pto-like topology.
AB  - A combination of topological rules and quantum chemical calculations has
      facilitated the development of a rational metal-organic framework (MOF) synthetic
      strategy using the tritopic benzene-1,3,5-tribenzoate (btb) linker and a neutral
      cross-linker 4,4'-bipyridine (bipy). A series of new compounds, namely
      [M(2)(bipy)](3)(btb)(4) (DUT-23(M), M = Zn, Co, Cu, Ni),
      [Cu(2)(bisqui)(0.5)](3)(btb)(4) (DUT-24, bisqui = diethyl (R,S)-4,4'-biquinoline
      3,3'-dicarboxylate), [Cu(2)(py)(1.5)(H(2)O)(0.5)](3)(btb)(4) (DUT-33, py =
      pyridine), and [Cu(2)(H(2)O)(2)](3)(btb)(4) (DUT-34), with high specific surface
      areas and pore volumes (up to 2.03 m(3)  g(-1) for DUT-23(Co)) were synthesized.
      For DUT-23(Co), excess storage capacities were determined for methane (268 mg g(
      1) at 100 bar and 298 K), hydrogen (74 mg g(-1) at 40 bar and 77 K), and n-butane
      (99 mg g(-1) at 293 K). DUT-34 is a non-cross-linked version of DUT-23 (non
      interpenetrated pendant to MOF-14) that possesses open metal sites and can
      therefore be used as a catalyst. The accessibility of the pores in DUT-34 to
      potential substrate molecules was proven by liquid phase adsorption. By
      exchanging the N,N donor 4,4'-bipyridine with a substituted racemic biquinoline,
      DUT-24 was obtained. This opens a route to the synthesis of a chiral compound,
      which could be interesting for enantioselective separation.

PMID- 21956517
TI  - Subtrochanteric/femoral shaft versus hip fractures: incidences and identification
      of risk factors.
AB  - Subtrochanteric and femoral shaft (ST/FS) fractures are now considered to be
      fragility fractures in osteoporotic patients. Although rare, there is growing
      evidence of the burden that they constitute. Little is known about the change
      over time in incidence of ST/FS fractures. We assessed the incidence of ST/FS
      fractures and the associated risk factors from 2002 to 2009 compared with those
      of hip fractures. Data were obtained from the French National Database, which
      includes all hospital discharge codes from acute care facilities.
      Hospitalizations for primary surgical management of neck/trochanteric (hip) and
      ST/FS fractures in patients aged above 50 years were selected and described for
      different age groups. Incidences per million populations were calculated using
      the estimated French population adjusted for each year, age, and gender. We
      studied the change for each fracture site. The comorbidity factors related to
      these fractures were assessed in 2009 using multivariate logistic regression.
      From 2002 to 2009, the adjusted incidence of hip fractures decreased continuously
      from 4368 to 3662 in women (p < 0.0001), and a mild increase from 1476 to 1384 in
      men (p < 0.0001) after an initial decrease. In contrast, the incidence of ST/FS
      increased significantly in both genders (from 353 to 395 in women, from 146 to
      159 in men). In 2009, the incidence of ST/FS in the general population remained
      low, reaching the levels of 412 in women and 168 in men, but were 2966 and 1461
      in women and men aged >89 years. The adjusted risk of having a ST/FS fracture was
      significantly higher in a context of obesity (odds ratio [OR]: 2.26; 1.95-2.61)
      and dementia (OR: 1.23; 1.16-1.30), but decreased with age (OR: 0.83; 0.79-0.88)
      and hypertension (OR: 0.90; 0.86-0.95). In conclusion, ST/FS fractures mainly
      affect elderly people and incidence increased significantly from 2002 to 2009.
      Obesity and dementia are the risk factors associated with these rare fractures,
      compared with regular hip fractures.

PMID- 21956518
TI  - Pituitary resistance to thyroid hormones: pathophysiology and therapeutic
      options.
AB  - Thyroid hormone secretion suppresses the expression of thyroid stimulating
      hormone (TSH), both of which are strictly controlled by a negative feedback loop
      between the hypothalamus-pituitary and thyroid. Pituitary resistance to thyroid
      hormone (PRTH) is defined as resistance to the action of thyroid hormone that is
      more severe in the pituitary than at the peripheral tissue level. Although the
      molecular basis of PRTH is not well understood, the clinical issue mainly
      involves imbalance between the hypothalamus-pituitary and peripheral thyroid
      hormone responsivity, which may induce peripheral thyrotoxic phenomena. Here, we
      review the pathogenesis and molecular aspects of PRTH, present a single case with
      inappropriate TSH secretion suffering from thyrotoxicosis treated with PTU, and
      discuss the possible choice of therapeutic options to correct the imbalance of
      thyroid hormone responsivity in both the hypothalamus-pituitary and peripheral
      tissues.

PMID- 21956519
TI  - Radiology Report Comparator: a novel method to augment resident education.
AB  - Attending radiologists routinely edit radiology trainee dictated preliminary
      reports as part of standard workflow models. Time constraints, high volume, and
      spatial separation may not always facilitate clear discussion of these changes
      with trainees. However, these edits can represent significant teaching moments
      that are lost if they are not communicated back to trainees. We created an
      electronic method for retrieving and displaying changes made to resident written
      preliminary reports by attending radiologists during the process of radiology
      report finalization. The Radiology Information System is queried. Preliminary and
      final radiology reports, as well as report metadata, are extracted and stored in
      a database indexed by accession number and trainee/radiologist identity. A web
      application presents to trainees their 100 most recent preliminary and final
      report pairs both side by side and in a "track changes" mode. Web utilization
      audits showed regular utilization by trainees. Surveyed residents stated they
      compared reports for educational value, to improve future reports, and to improve
      patient care. Residents stated that they compared reports more frequently after
      deployment of this software solution and that regular assessment of their work
      using the Report Comparator allowed them to routinely improve future report
      quality and improved radiological understanding. In an era with increasing
      workload demands, trainee work hour restrictions, and decentralization of
      department resources (e.g., faculty, PACS), this solution helps to retain an
      important part of the educational experience that would have otherwise run the
      risk of being lost and provides it to the trainees in an efficient and highly
      consumable manner.

PMID- 21956520
TI  - Water droplet bouncing--a definition for superhydrophobic surfaces.
AB  - The ability of water to bounce on a surface provides an indication of many of the
      surface's properties. The technique described in this article uses water bouncing
      to determine the hydrophobicity of a surface, with a relationship established
      between water contact angle and number of bounces, which is dependent on the
      surfaces microstructure.

PMID- 21956521
TI  - Wide-range color tuning of iridium biscarbene complexes from blue to red by
      different N?N ligands: an alternative route for adjusting the emission colors.

PMID- 21956522
TI  - Synthesis and biological evaluation of novel homocamptothecins conjugating with
      dihydropyrimidine derivatives as potent topoisomerase I inhibitors.
AB  - Homocamptothecin (hCPT) is a camptothecin (CPT) homologue with the insertion of a
      methylene (CH2) spacer between the alcohol moiety and carbonyl group of the
      classical six-membered alpha-hydroxylactone ring. This modification provides
      higher lactone stability and did not impair its activity against topoisomerase I
      (Topo I), but rather appears to improve it compared to CPT. In an attempt to
      improve the antitumor activity of homocamptothecins, a series of novel hCPT
      derivatives conjugating with dihydropyrimidine (DHPM) derivatives was designed
      and synthesized based on a synthetic route which couples 7-formylhomocamptothecin
      with different dihydropyrimidine derivates. Most of the synthesized compounds
      exhibited good antiproliferative activity on tumor cell lines A549, MDA-MB-435
      and HCT116. Furthermore, this class of compounds showed superior Topo I
      inhibition activity comparable to or higher than CPT.

PMID- 21956523
TI  - Pralatrexate: a novel synthetic antifolate for relapsed or refractory peripheral
      T-cell lymphoma and other potential uses.
AB  - PURPOSE: The pharmacology, pharmacokinetics, clinical trials, adverse effects,
      dosage, and economic considerations of pralatrexate (PDX) are reviewed. SUMMARY:
      Peripheral T-cell lymphoma (PTCL) comprises approximately 15-20% of all
      aggressive lymphomas and 5-10% of all non-Hodgkin's lymphomas. Advanced PTCL is
      often refractory to traditional first-line chemotherapy regimens. PDX was
      developed as a synthetic folate analog antimetabolite that competitively inhibits
      dihydrofolate reductase (DHFR). This results in the depletion of thymidine,
      leading to interference with deoxyribonucleic acid synthesis and cancer cell
      death. PDX has a higher potency than methotrexate and edatrexate (EDX). The
      efficacy and safety of PDX have been demonstrated in the PROPEL trial, a
      prospective phase II trial in patients with relapsed or refractory PTCL. Patients
      with prior stem cell transplantation receiving PDX also had similar response
      rates (RRs). PDX was investigated on the treatment of relapsed or refractory
      cutaneous T-cell lymphoma, previously treated advanced non-small cell lung cancer
      and other solid malignancies. PDX has similar side effects to other DHFR
      inhibitors. The most common side effect of PDX is mucositis. The recommended dose
      of PDX is 30 mg/m(2) weekly once for 6 weeks in 7-week cycle until disease
      progresses or unacceptable toxicity for PTCL and may require dose reduction or
      discontinuation. Patients should be supplemented with oral folic acid and
      intramuscular vitamin B(12) injections. CONCLUSION: PDX provides clinical benefit
      to patients with relapsed or refractory PTCL with durable complete and partial
      responses in patients who had not responded to multiple prior treatment regimens.

PMID- 21956524
TI  - Analysis and occurrence of emerging chlorinated and brominated flame retardants
      in surficial sediment of the Dalian coastal area in China.
AB  - The concentrations and distributions of some typical chlorinated flame retardants
      (Dechlorane or Mirex, Dechlorane 602 (Dec 602), Dechlorane 603 (Dec 603),
      Dechlorane 604 (Dec 604) and Dechlorane Plus (DP)) and brominated FRs
      (polybrominated diphenyl ethers (PBDEs), pentabromoethylbenzene (PBEB) and 1,2
      bis(2,4,6-tribromophenoxy)ethane (BTBPE)) were analyzed in surficial sediment
      collected from the Dalian coastal area in northeast China. Dec 603, Dec 604, and
      BTBPE were below their respective limits of detection (LOD) in all sediment
      samples, while Dechlorane, Dec 602, DP, Sigma13BDE (tri- to hepta-BDEs), BDE 209,
      and PBEB were identified in the ranges <0.015-39.9 ng g(-1) dry weight (dw),
      <0.011-0.156 ng g(-1) dw, 0.69-7.00 ng g(-1) dw, 0.017-1.33 ng g(-1) dw, 3.94-103
      ng g(-1) dw, and <0.073-1.9 ng g(-1) dw, respectively. Relationships between
      these chlorinated and brominated FRs were analyzed using Pearson's correlation
      and principal component analysis (PCA). DP, Dechlorane, Sigma13BDE, and BDE 209
      showed significantly positive correlation (p<0.05), and these relationships
      showed excellent agreement with PCA results. The spatial trends for Dechlorane,
      DP, BDE 209, and Sigma13BDE showed that high concentrations were found in the
      industrial zone and lower concentrations in residential and garden zones. The
      results imply that these FRs are originating from a common source, and support
      the view that direct input from the effluent of sewage outlets is a major source
      of these compounds in Dalian sediment.

PMID- 21956525
TI  - Inhibitor-2 induced M-phase arrest in Xenopus cycling egg extracts is dependent
      on MAPK activation.
AB  - The evolutionarily-conserved protein phosphatase 1 (PP1) plays a central role in
      dephosphorylation of phosphoproteins during the M phase of the cell cycle. We
      demonstrate here that the PP1 inhibitor inhibitor-2 protein (Inh-2) induces an M
      phase arrest in Xenopus cycling egg extracts. Interestingly, the characteristics
      of this M-phase arrest are similar to those of mitogen-activated protein kinase
      (p42MAPK)-induced M-phase arrest. This prompted us to investigate whether Inh-2
      induced M-phase arrest was dependent on activation of the p42MAPK pathway. We
      demonstrate here that MAPK activity is required for Inh-2-induced M-phase arrest,
      as inhibition of MAPK by PD98059 allowed cycling extracts to exit M phase,
      despite the presence of Inh-2. We next investigated whether Inh-2 phosphorylation
      by the MAPK pathway was required to induce an M-phase arrest. We discovered that
      while p90Rsk (a MAPK protein required for M-phase arrest) is able to
      phosphorylate Inh-2, this phosphorylation is not required for Inh-2 function.
      Overall, our results suggest a novel mechanism linking p42MAPK and PP1 pathways
      during M phase of the cell cycle.

PMID- 21956526
TI  - Prognostic significance of home arterial stiffness index derived from self
      measurement of blood pressure: the Ohasama Study.
AB  - BACKGROUND: Arterial stiffness is a stroke risk factor. The home arterial
      stiffness index (HASI) can be calculated from self-measured blood pressure using
      the same formula as the calculation of ambulatory arterial stiffness index
      (AASI). METHODS: In 2,377 inhabitants (baseline age, 35-96 years) without a
      history of stroke, home blood pressure was measured once every morning for 26
      days (median). HASI was defined as 1 minus the regression slope of diastolic over
      systolic on home blood pressure in individual subjects. The standardized hazard
      ratio (HR) of HASI was computed for cerebral infarction, while adjusting for sex,
      age, body mass index, pulse pressure, mean arterial pressure, heart rate, day-by
      day variability of systolic blood pressure, smoking and drinking habits, serum
      total cholesterol, diabetes mellitus, and antihypertensive treatment. RESULTS: A
      total of 191 (8.0%) cerebral infarctions and 75 (3.2%) hemorrhagic strokes
      occurred over a median of 13.8 years. Mean +/- s.d. of HASI was 0.60 +/- 0.23
      units. An increase in HASI of 1 s.d. was associated with an increased HR for
      cerebral infarction in all subjects (1.19, P = 0.034), men (1.37, P = 0.002), and
      normotensive subjects (1.46, P = 0.006), but not in women or hypertensive
      patients (P > 0.56). For hemorrhagic stroke, HASI was not prognostic.
      CONCLUSIONS: HASI predicted cerebral infarction independent of pulse pressure and
      other risk factors in men and normotensive subjects. One important role of home
      blood pressure measurement is early recognition of onset of hypertension in
      normotensive subjects who are at risk of developing hypertension. HASI provides
      additional benefits for such subjects.

PMID- 21956527
TI  - Remodeling of retinal small arteries in hypertension.
AB  - Vascular dysfunction due to elevated blood pressure constitutes an early step in
      the pathogenesis of atherosclerotic disease. A better understanding of the
      pathophysiology and of clinical correlates of vascular remodeling in retinal
      arteries and arterioles offers the opportunity for a better risk stratification
      and treatment. In vivo vascular changes can be best detected by direct imaging
      techniques. In this review, we summarize the main findings of several recent
      studies analyzing retinal-arteriolar parameters, such as outer diameter (OD) and
      lumen diameter (LD), retinal capillary flow (RCF), wall-to-lumen-ratio, and wall
      cross-sectional area by using scanning laser Doppler flowmetry (SLDF). Blood
      pressure emerged as an independent determinant of the wall-to-lumen ratio (WLR)
      of retinal arterioles. Retinal arterioles and small arteries of hypertensive
      subjects showed eutrophic inward remodeling as indicated by increased WLR,
      decreased LD and almost unchanged wall cross-sectional area compared to
      normotensive subjects. These findings are in accordance with those observed in
      small-resistance vessels analyzed ex vivo. In hypertensive patients, an increased
      retinal vascular resistance has been documented and basal nitric oxide activity
      emerged as an independent determinant of early arteriolar remodeling. Thus, SLDF
      emerged as a noninvasive research tool to assess early vascular changes in the
      retinal circulation.

PMID- 21956528
TI  - Thresholds of ambulatory blood pressure associated with chronic complications in
      type 2 diabetes.
AB  - BACKGROUND: Diagnostic cut-off values for ambulatory blood pressure monitoring
      (ABPM) in diabetic patients are not established. The aim was to investigate
      associations between office and ambulatory blood pressures (BPs) and diabetic
      chronic complications and to establish optimal threshold ambulatory BP values
      regarding the likehood of having microvascular complications in type 2 diabetes.
      METHODS: In a cross-sectional design, clinical, laboratory, and 24-h ABPM data
      were obtained in 550 type 2 diabetic patients. Multivariate logistic regression
      assessed the associations between office and ambulatory BPs and diabetic micro
      and macrovascular complications. Optimal threshold values for ambulatory BPs
      (daytime, night-time, and 24 h) were established by examining the best
      combination of systolic (SBP) and diastolic BP (DBP) that maximized the odds
      ratios (ORs) of having each microvascular complication. RESULTS: After
      multivariate adjustment for all potential confounders, ambulatory SBPs were more
      strongly associated with diabetic complications than office BPs, except for
      retinopathy and nephropathy, in which both were equivalent. In general, night
      time BPs were stronger correlates than daytime BPs. The optimal threshold
      ambulatory BP values were 125/75 mm Hg for daytime, 110/65 mm Hg for night-time,
      and 120/75 mm Hg for the 24-h period, with odds ranging from 1.7- to 2.3-fold of
      having each microvascular complication. CONCLUSIONS: Except for retinopathy and
      advanced nephropathy, ambulatory BPs are better correlates of chronic
      complications than office BPs in type 2 diabetes. The association of
      microvascular complications with lower ambulatory BP levels than those reported
      as normal for nondiabetic patients may indicate that lower cut-off values for
      ambulatory BPs might be considered in type 2 diabetic patients.

PMID- 21956529
TI  - Aerobic exercise training in heart failure: impact on sympathetic hyperactivity
      and cardiac and skeletal muscle function.
AB  - Heart failure is a common endpoint for many forms of cardiovascular disease and a
      significant cause of morbidity and mortality. Chronic neurohumoral excitation
      (i.e., sympathetic hyperactivity) has been considered to be a hallmark of heart
      failure and is associated with a poor prognosis, cardiac dysfunction and
      remodeling, and skeletal myopathy. Aerobic exercise training is efficient in
      counteracting sympathetic hyperactivity and its toxic effects on cardiac and
      skeletal muscles. In this review, we describe the effects of aerobic exercise
      training on sympathetic hyperactivity, skeletal myopathy, as well as cardiac
      function and remodeling in human and animal heart failure. We also discuss the
      mechanisms underlying the effects of aerobic exercise training.

PMID- 21956530
TI  - Cardiovascular and autonomic modulation by the central nervous system after
      aerobic exercise training.
AB  - The autonomic nervous system plays a key role in maintaining homeostasis under
      normal and pathological conditions. The sympathetic tone, particularly for the
      cardiovascular system, is generated by sympathetic discharges originating in
      specific areas of the brainstem. Aerobic exercise training promotes several
      cardiovascular adjustments that are influenced by the central areas involved in
      the output of the autonomic nervous system. In this review, we emphasize the
      studies that investigate aerobic exercise training protocols to identify the
      cardiovascular adaptations that may be the result of central nervous system
      plasticity due to chronic exercise. The focus of our study is on some groups of
      neurons involved in sympathetic regulation. They include the nucleus tractus
      solitarii, caudal ventrolateral medulla and the rostral ventrolateral medulla
      that maintain and regulate the cardiac and vascular autonomic tonus. We also
      discuss studies that demonstrate the involvement of supramedullary areas in
      exercise training modulation, with emphasis on the paraventricular nucleus of the
      hypothalamus, an important area of integration for autonomic and neuroendocrine
      responses. The results of these studies suggest that the beneficial effects of
      physical activity may be due, at least in part, to reductions in sympathetic
      nervous system activity. Conversely, with the recent association of physical
      inactivity with chronic disease, these data may also suggest that increases in
      sympathetic nervous system activity contribute to the increased incidence of
      cardiovascular diseases associated with a sedentary lifestyle.

PMID- 21956531
TI  - Influence of eNOS gene polymorphism on cardiometabolic parameters in response to
      physical training in postmenopausal women.
AB  - The health-promoting effects of exercise training (ET) are related to nitric
      oxide (NO) production and/or its bioavailability. The objective of this study was
      to determine whether single nucleotide polymorphism of the endothelial NO
      synthase (eNOS) gene at positions -786T>C, G894T (Glu298Asp) and at the variable
      number of tandem repeat (VNTR) Intron 4b/a would interfere with the
      cardiometabolic responses of postmenopausal women submitted to physical training.
      Forty-nine postmenopausal women were trained in sessions of 30-40 min, 3 days a
      week for 8 weeks. Genotypes, oxidative stress status and cardiometabolic
      parameters were then evaluated in a double-blind design. Both systolic and
      diastolic blood pressure values were significantly reduced after ET, which was
      genotype-independent. However, women without eNOS gene polymorphism at position 
      786T>C (TT genotype) and Intron 4b/a (bb genotype) presented a better reduction
      of total cholesterol levels (-786T>C: before = 213 +/- 12.1, after = 159.8 +/-
      14.4, Delta = -24.9% and Intron 4b/a: before = 211.8 +/- 7.4, after = 180.12 +/-
      6.4 mg/dL, Delta = -15%), and LDL cholesterol (-786T>C: before = 146.1 +/- 13.3,
      after = 82.8 +/- 9.2, Delta = -43.3% and Intron 4b/a: before = 143.2 +/- 8, after
      = 102.7 +/- 5.8 mg/dL, Delta = -28.3%) in response to ET compared to those who
      carried the mutant allele. Superoxide dismutase activity was significantly
      increased in trained women whereas no changes were observed in malondialdehyde
      levels. Women without eNOS gene polymorphism at position -786T>C and Intron 4b/a
      showed a greater reduction of plasma cholesterol levels in response to ET.
      Furthermore, no genotype influence was observed on arterial blood pressure or
      oxidative stress status in this population.

PMID- 21956532
TI  - Involvement of catecholaminergic medullary pathways in cardiovascular responses
      to acute changes in circulating volume.
AB  - Water deprivation and hypernatremia are major challenges for water and sodium
      homeostasis. Cellular integrity requires maintenance of water and sodium
      concentration within narrow limits. This regulation is obtained through
      engagement of multiple mechanisms and neural pathways that regulate the volume
      and composition of the extracellular fluid. The purpose of this short review is
      to summarize the literature on central neural mechanisms underlying
      cardiovascular, hormonal and autonomic responses to circulating volume changes,
      and some of the findings obtained in the last 12 years by our laboratory. We
      review data on neural pathways that start with afferents in the carotid body that
      project to medullary relays in the nucleus tractus solitarii and caudal
      ventrolateral medulla, which in turn project to the median preoptic nucleus in
      the forebrain. We also review data suggesting that noradrenergic A1 cells in the
      caudal ventrolateral medulla represent an essential link in neural pathways
      controlling extracellular fluid volume and renal sodium excretion. Finally,
      recent data from our laboratory suggest that these structures may also be
      involved in the beneficial effects of intravenous infusion of hypertonic saline
      on recovery from hemorrhagic shock.

PMID- 21956533
TI  - Gender-dependent effects of aging on the kidney.
AB  - It is well known that the kidney plays an important role in the development of
      cardiovascular diseases such as hypertension. The normal aging process leads to
      changes in kidney morphology, hemodynamics and function, which increase the
      incidence of cardiovascular events in the elderly population. These disturbances
      are influenced by several factors, including gender. In general, females are
      protected by the effects of estrogens on the cardiorenal system. Several studies
      have demonstrated the beneficial effects of estrogens on renal function in the
      elderly; however, the relationships between androgens and kidney health during
      one's lifetime are not well understood. Sex steroids have many complex actions,
      and the decline in their levels during aging clearly influences kidney function,
      decreases the renal reserve and facilitates the development of cardiovascular
      disorders. Therefore, in this review, we discuss the cellular, biochemical, and
      molecular mechanisms by which sex hormones may influence renal function during
      the aging process.

PMID- 21956534
TI  - Alternative pathways for angiotensin II generation in the cardiovascular system.
AB  - The classical renin-angiotensin system (RAS) consists of enzymes and peptides
      that regulate blood pressure and electrolyte and fluid homeostasis. Angiotensin
      II (Ang II) is one of the most important and extensively studied components of
      the RAS. The beneficial effects of angiotensin converting enzyme (ACE) inhibitors
      in the treatment of hypertension and heart failure, among other diseases, are
      well known. However, it has been reported that patients chronically treated with
      effective doses of these inhibitors do not show suppression of Ang II formation,
      suggesting the involvement of pathways alternative to ACE in the generation of
      Ang II. Moreover, the finding that the concentration of Ang II is preserved in
      the kidney, heart and lungs of mice with an ACE deletion indicates the important
      role of alternative pathways under basal conditions to maintain the levels of Ang
      II. Our group has characterized the serine protease elastase-2 as an alternative
      pathway for Ang II generation from Ang I in rats. A role for elastase-2 in the
      cardiovascular system was suggested by studies performed in heart and conductance
      and resistance vessels of normotensive and spontaneously hypertensive rats. This
      mini-review will highlight the pharmacological aspects of the RAS, emphasizing
      the role of elastase-2, an alternative pathway for Ang II generation.

PMID- 21956535
TI  - Endothelial dysfunction in cardiovascular and endocrine-metabolic diseases: an
      update.
AB  - The endothelium plays a vital role in maintaining circulatory homeostasis by the
      release of relaxing and contracting factors. Any change in this balance may
      result in a process known as endothelial dysfunction that leads to impaired
      control of vascular tone and contributes to the pathogenesis of some
      cardiovascular and endocrine/metabolic diseases. Reduced endothelium-derived
      nitric oxide (NO) bioavailability and increased production of thromboxane A2,
      prostaglandin H2 and superoxide anion in conductance and resistance arteries are
      commonly associated with endothelial dysfunction in hypertensive, diabetic and
      obese animals, resulting in reduced endothelium-dependent vasodilatation and in
      increased vasoconstrictor responses. In addition, recent studies have
      demonstrated the role of enhanced overactivation of beta-adrenergic receptors
      inducing vascular cytokine production and endothelial NO synthase (eNOS)
      uncoupling that seem to be the mechanisms underlying endothelial dysfunction in
      hypertension, heart failure and in endocrine-metabolic disorders. However, some
      adaptive mechanisms can occur in the initial stages of hypertension, such as
      increased NO production by eNOS. The present review focuses on the role of NO
      bioavailability, eNOS uncoupling, cyclooxygenase-derived products and pro
      inflammatory factors on the endothelial dysfunction that occurs in hypertension,
      sympathetic hyperactivity, diabetes mellitus, and obesity. These are
      cardiovascular and endocrine-metabolic diseases of high incidence and mortality
      around the world, especially in developing countries and endothelial dysfunction
      contributes to triggering, maintenance and worsening of these pathological
      situations.

PMID- 21956536
TI  - Hypertensive effects of the iv administration of picomoles of ouabain.
AB  - Ouabain, an endogenous digitalis compound, has been detected in nanomolar
      concentrations in the plasma of several mammals and is associated with the
      development of hypertension. In addition, plasma ouabain is increased in several
      hypertension models, and the acute or chronic administration of ouabain increases
      blood pressure in rodents. These results suggest a possible association between
      ouabain and the genesis or development and maintenance of arterial hypertension.
      One explanation for this association is that ouabain binds to the alpha-subunit
      of the Na(+) pump, inhibiting its activity. Inhibition of this pump increases
      intracellular Na(+), which reduces the activity of the sarcolemmal Na(+)/Ca(2+)
      exchanger and thereby reduces Ca(2+) extrusion. Consequently, intracellular
      Ca(2+) increases and is taken up by the sarcoplasmic reticulum, which, upon
      activation, releases more calcium and increases the vascular smooth muscle tone.
      In fact, acute treatment with ouabain enhances the vascular reactivity to
      vasopressor agents, increases the release of norepinephrine from the perivascular
      adrenergic nerve endings and promotes increases in the activity of endothelial
      angiotensin-converting enzyme and the local synthesis of angiotensin II in the
      tail vascular bed. Additionally, the hypertension induced by ouabain has been
      associated with central mechanisms that increase sympathetic tone, subsequent to
      the activation of the cerebral renin-angiotensin system. Thus, the association
      with peripheral mechanisms and central mechanisms, mainly involving the renin
      angiotensin system, may contribute to the acute effects of ouabain-induced
      elevation of arterial blood pressure.

PMID- 21956537
TI  - Prognostic significance of CD24 and claudin-7 immunoexpression in ductal invasive
      breast cancer.
AB  - This study aimed to identify the CD24 and CD44 immunophenotypes within invasive
      ductal breast carcinoma (IDC) subgroups defined by immunohistochesmistry markers
      and to determine its influence on prognosis as well as its association with the
      expression of Ki-67, cytokeratins (CK5 and CK18) and claudin-7.
      Immunohistochemical expression of CD44 and CD24 alone or in combination was
      investigated in 95 IDC cases arranged in a tissue microarray (TMA). The
      association with subgroups defined as luminal A and B; HER2 rich and triple
      negative, or with the other markers and prognosis was analyzed. CD44+/CD24- and
      CD44-/CD24+ were respectively present in 8.4% and 16.8% of the tumors, a lack of
      both proteins was detected in 6.3%, while CD44+/CD24+ was observed in 45.3% of
      the tumors. Although there was no significant correlation between subgroups and
      different phenotypes, the CD44+/CD24- phenotype was more common in the basal
      subgroups but absent in HER2 tumors, whereas luminal tumors are enriched in CD44
      /CD24+ and CD44+/CD24+ cells. The frequency of CD44+/CD24- or CD44-/CD24+ was not
      associated with clinical characteristics or biological markers. There was also no
      significant association of these phenotypes with the event free (DFS) and overall
      survival (OS). Single CD44+ was evident in 57.9% of the tumors and was marginally
      associated to grading and not to any other tumor characteristics as well as OS
      and DFS. CD24+ was positive in 74.7% of the tumors, showing a significant
      association with estrogen receptor, progesterone receptor and Ki-67 and a
      marginal association with CK18 and claudin-7. Expression of claudin-7 and Ki-67
      did not associate with the cancer subgroups, while a positive association between
      CK18 and the luminal subgroups was found (P=0.03). CK5, CK18 and Ki-67 expression
      had no influence in OS or DFS. Single CD24+ (P=0.07) and claudin-7 positivity
      (P=0.05) were associated with reduced time of recurrence, suggesting a
      contribution of these markers to aggressiveness of breast cancer.

PMID- 21956538
TI  - Clickable functionalization of liposomes with the gH625 peptide from Herpes
      simplex virus type I for intracellular drug delivery.
AB  - Liposomes externally modified with the nineteen residues gH625 peptide,
      previously identified as a membrane-perturbing domain in the gH glycoprotein of
      Herpes simplex virus type I, have been prepared in order to improve the
      intracellular uptake of an encapsulated drug. An easy and versatile synthetic
      strategy, based on click chemistry, has been used to bind, in a controlled way,
      several copies of the hydrophobic gH625 peptide on the external surface of 1,2
      dioleoyl-sn-glycero-3-phosphocholine (DOPG)-based liposomes. Electron
      paramagnetic resonance studies, on liposomes derivatized with gH625 peptides,
      which are modified with the 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4
      carboxylic acid (TOAC) spin label in several peptide positions, confirm the
      positioning of the coupled peptides on the liposome external surface, whereas
      dynamic light scattering measurements indicate an increase of the diameter of the
      liposomes of approximately 30% after peptide introduction. Liposomes have been
      loaded with the cytotoxic drug doxorubicin and their ability to penetrate inside
      cells has been evaluated by confocal microscopy experiments. Results suggest that
      liposomes functionalized with gH625 may act as promising intracellular targeting
      carriers for efficient delivery of drugs, such as chemotherapeutic agents, into
      tumor cells.

PMID- 21956539
TI  - A computational investigation and the conformational analysis of dimers, anions,
      cations, and zwitterions of L-phenylalanine.
AB  - The structure and stability of various conformations of L-phenylalanine (PheN)
      and its zwitterions (PheZ), along with their ionized counterparts, cation (PheC)
      and anion (PheA), generated by adding and removing a proton respectively, have
      been investigated using first principle calculations in vacuum and in solution.
      This is followed by an extensive study on various possible dimer (PheD)
      conformations, which are noncovalently bound units without a peptide bond. This
      study results in 52, 31, 12, 9, and 11 minimum energy structures on the potential
      energy surfaces of PheD, PheN, PheC, PheA, and PheZ, respectively. Several
      important nonbonded interactions such as hydrogen bonds, NH-pi, CH-pi, OH-pi, and
      pi-pi interactions, which impart stability to the monomeric and dimeric units,
      have been analyzed. The capability and strength of the nonbonded interactions
      drastically changing the conformational orientations of monomeric units has been
      illustrated.

PMID- 21956540
TI  - Disaster Victim Identification: quality management from an odontology
      perspective.
AB  - The desired outcome of the victim identification component of a mass fatality
      event is correct identification of deceased persons in a timely manner allowing
      legal and social closure for relatives of the victims. Quality Management across
      all aspects of the Disaster Victim Identification (DVI) structure facilitates
      this process. Quality Management in forensic odontology is the understanding and
      implementation of a methodology that ensures collection, collation and
      preservation of the maximum amount of available dental data and the appropriate
      interpretation of that data to achieve outcomes to a standard expected by the DVI
      instructing authority, impacted parties and the forensic odontology specialist
      community. Managerial pre-event planning responsibility, via an odontology
      coordinator, includes setting a chain of command, developing and reviewing
      standard operating procedures (SOP), ensuring use of current scientific
      methodologies and staff training. During a DVI managerial responsibility includes
      tailoring SOP to the specific situation, ensuring member accreditation,
      encouraging inter-disciplinary cooperation and ensuring security of odontology
      data and work site. Individual responsibilities include the ability to work
      within a team, accept peer review, and share individual members' skill sets to
      achieve the best outcome. These responsibilities also include adherence to chain
      of command and the SOP, maintenance of currency of knowledge and recognition of
      professional boundaries of expertise. This article highlights issues of Quality
      Management pertaining particularly to forensic odontology but can also be
      extrapolated to all DVI actions.

PMID- 21956541
TI  - Reproductive factors and Parkinson's disease: a multicenter case-control study.
AB  - BACKGROUND: The objective of this study was to evaluate the possible association
      between endogenous and exogenous estrogens and Parkinson's disease (PD). METHODS:
      The FRAGAMP study is a large Italian multicenter case-control study. PD was
      diagnosed according to Gelb's criteria. A standardized questionnaire was
      administered to record demographic, epidemiological, and clinical data. Adjusted
      ORs and 95% CIs were estimated using multivariate analysis (logistic regression).
      RESULTS: Two hundred PD women (mean age, 68.0 +/- 9.5 years) and 299 control
      women (mean age, 61.8 +/- 9.9 years) were enrolled in the study. Age at menarche,
      age at menopause, fertile life duration, cumulative duration of pregnancies,
      hormone replacement therapy, and surgical menopause were not significantly
      associated with PD. Multivariate analysis showed a significant positive
      association between use of oral contraceptives and PD, with an adjusted OR of
      3.27 (95% CI, 1.24-8.59; P = .01). CONCLUSIONS: Our data suggest that oral
      contraceptives could increase the risk of PD.

PMID- 21956543
TI  - Oncocytic lesions (oncocytoma) of the ocular adnexa:  report of 15 cases and
      review of literature.
AB  - PURPOSE: To describe the clinical, imaging, and pathology features of oncocytic
      lesions in the ocular adnexa. METHODS: Retrospective, noncomparative,
      interventional case series. RESULTS: Fifteen oncocytic neoplasms (n = 15
      patients) were classified as oncocytoma in 14 (93%) and oncocytic hyperplasia in
      1 (7%). The mean patient age was 66 years (median = 66, range = 44-82), and 9
      (60%) were male. The tumor involved the caruncle (n = 13, 86%), bulbar
      conjunctiva (n = 1, 7%), and plica semilunaris (n = 1, 7%). All cases were
      unifocal and most often presented as a painless mass (n = 12, 80%), evolving over
      a median 6 months (mean = 12, range = 1-48 months). The mean tumor base was 4.1
      mm (median = 4.0, range = 1-10), and the tumor was well-circumscribed (n = 14),
      dark blue (n = 7), and cystic (n = 10). Ultrasound biomicroscopy and anterior
      segment optical coherence tomography disclosed mixed solid and cystic components.
      Complete surgical excision was curative without recurrence after a mean follow up
      of 39 months. Histopathology disclosed columnar cells with copious quantities of
      intensely eosinophilic cytoplasm in the lining epithelium (oncocytic hyperplasia)
      and in some cases with cystadenomatous proliferation (oncocytoma). CONCLUSION:
      Oncocytic lesions of the ocular adnexae are typically well-circumscribed, cystic
      lesions that most often involve the caruncle. Surgical excision can be curative.
      Epithelial cells with copious quantities of intensely eosinophilic cytoplasm
      characterize oncocytic transformation histopathologically.

PMID- 21956542
TI  - Delayed short-course treatment with teriparatide (PTH(1-34)) improves femoral
      allograft healing by enhancing intramembranous bone formation at the graft-host
      junction.
AB  - Clinical management of critical bone defects remains a major challenge. Despite
      preclinical work demonstrating teriparatide (PTH(1-34)) effectiveness in small
      animals, inconclusive data from clinical trials have raised questions of dose and
      regimen. To address this, we completed a comprehensive study in the murine
      femoral allograft model, to assess the effects of dose (0.4, 4, and 40 ug/kg/day)
      and various treatment regimens on radiographic, histologic, and biomechanical
      healing at 2, 4, and 9 weeks. Only the high dose (40 ug/kg) of PTH(1-34)
      demonstrated significant effects when given daily over 9 weeks. Remarkably,
      equivalent biomechanical results were obtained with delayed, short treatment from
      2 to 6 weeks that did not induce a significant increase in endochondral bone
      formation and callus volume. In contrast, PTH(1-34) treatment from 1 to 5 weeks
      postop demonstrated similar osteogenic effects as immediate daily treatment for 9
      weeks, but failed to achieve a significant increase in biomechanics at 9 weeks.
      MicroCT and histologic analyses demonstrated that the 2-week delay in treatment
      allowed for timely completion of the endochondral phase, such that the prominent
      effects of PTH(1-34) were enhanced intramembranous bone formation and remodeling
      at the graft-host junction. These findings support the potential use of PTH(1-34)
      as an adjuvant therapy for massive allograft healing, and suggest that there may
      be an ideal treatment window in which a short course is administered after the
      endochondral phase to promote osteoblastic bone formation and remodeling to
      achieve superior union with modest callus formation.

PMID- 21956544
TI  - Marsupialization for lacrimal ductular cysts (dacryops):  a case series.
AB  - PURPOSE: To present the clinicopathological features and treatment outcomes of
      lacrimal ductular cysts managed with marsupialization. METHODS: Retrospective
      case review of 13 patients presenting with lacrimal ductular cysts. RESULTS:
      Thirteen patients were identified, of which 7 patients with full clinical data
      were included in the study, 4 female, 3 male, mean age 50 years. Their main
      presenting symptoms were superolateral orbital swelling, feeling of pressure on
      the eye, and lateral ptosis. Two patients had bilateral cysts, and the remaining
      5 had unilateral cysts. Six patients required surgical marsupialization, and one
      patient was treated conservatively because of preexisting dry eye. At surgery,
      one patient had multiple dacryoliths within the cyst. Histopathological analysis
      of the cyst lining in 5 out of 7 patients showed bilayered cuboidal epithelium
      with fibrous tissue. None of the patients had dry eye symptoms or signs after
      surgery. Follow-up ranged from 10 months to 2 years, mean 20 months CONCLUSION:
      Marsupialization is a safe and effective treatment for lacrimal ductular cysts.

PMID- 21956545
TI  - Subperiosteal abscess of the orbit:  duration of intravenous antibiotic therapy
      in nonsurgical cases.
AB  - PURPOSE: To report the duration of intravenous (IV) antibiotic administration and
      outcomes in a cohort of patients with subperiosteal abscess (SPA) of the orbit
      triaged to nonsurgical management. METHODS: A retrospective cohort study based on
      records of patients younger than 9 years admitted to a regional pediatric
      hospital with a diagnosis of orbital cellulitis from 1999 through 2008. Patients
      with computed tomography (CT)-confirmed SPA and associated sinusitis were
      included. Patients who underwent surgical drainage of sinuses and/or orbits
      during that admission were excluded. Patients discharged with a peripherally
      inserted central catheter for a predetermined treatment interval were excluded.
      Dates and times of first and last doses of inpatient IV antibiotics were
      recorded. Records were reviewed for evidence of hospital readmission for relevant
      diagnoses. Outcome measures included duration of IV antibiotic administration and
      hospital readmission. RESULTS: Forty-two patients met study criteria. Duration of
      IV treatment ranged from 2 to 8 days (mean and median, each 4 days). Forty-one
      patients were not readmitted with a relevant diagnosis from the time of hospital
      discharge to completion of data acquisition in April 2011. One patient was
      readmitted for recurrent acute infection 10 weeks after discharge and underwent
      urgent SPA and sinus drainage; review of the initial CT revealed an ethmoidal
      mucocoele. CONCLUSIONS: The duration of IV therapy associated with successful
      nonsurgical management of appropriately selected children with SPA is
      considerably shorter than that recommended in current pediatric infectious
      disease literature. The findings suggest that clinical judgment, based on each
      patient's initial CT findings and evolving signs, symptoms, and laboratory
      profile, should be a major determinant of IV intervals.

PMID- 21956546
TI  - Forensic fingerprinting and source identification of the 2009 Sarnia (Ontario)
      oil spill.
AB  - This paper presents a case study in which integrated forensic oil fingerprinting
      and data interpretation techniques were used to characterize the chemical
      compositions and determine the source of the 2009 Sarnia (Ontario) oil spill
      incident. The diagnostic fingerprinting techniques include determination of
      hydrocarbon groups and semi-quantitative product-type screening via gas
      chromatography (GC), analysis of oil-characteristic biomarkers and the extended
      suite of parent and alkylated PAH (polycyclic aromatic hydrocarbon) homologous
      series via gas chromatography-mass spectrometry (GC-MS), determination and
      comparison of a variety of diagnostic ratios of "source-specific marker"
      compounds, and determination of the weathering degree of the spilled oil, and
      whether the spilled oil hydrocarbons have been mixed with any other "background"
      chemicals (biogenic and/or pyrogenic hydrocarbons). The detailed chemical
      fingerprinting data and results reveal the following: (1) all four samples are
      mixtures of diesel and lubricating oil with varying percentages of diesel to lube
      oil. Both samples 1460 and 1462 are majority diesel-range oil mixed with a
      smaller portion of lube oil. Sample 1461 contains slightly less diesel-range oil.
      Sample 1463 is majority lubricating-range oil. (2) The diesel in the four
      diesel/lube oil mixture samples was most likely the same diesel and from the same
      source. (3) The spill sample 1460 and the suspected-source sample 1462 have
      nearly identical concentrations and distribution patterns of target analytes
      including TPHs, n-alkane, PAHs and biomarker compounds; and have nearly identical
      diagnostic ratios of target compounds as well. Furthermore, a perfect "positive
      match" correlation line (with all normalized ratio data points falling into the
      straight correlation line) is clearly demonstrated. It is concluded that the
      spill oil water sample 1460 (#1, from the water around the vessel enclosed by a
      boom) matches with the suspected source sample 1462 (#3, from the vessel engine
      room bilge pump). (4) From the n-alkane and PAH analysis, it appears that the oil
      in the spill sample 1460 is slightly more weathered in comparison with sample
      1462. The minor differences in fingerprints of two samples were most likely
      caused by weathering effects. (5) Sample 1461 (#2, from the vessel engine room
      bilge) and sample 1463 (#4, from the vessel bilge waste collection tank)
      demonstrated significantly different fingerprints and diagnostic ratios of target
      compounds from that of spill sample 1460. This was caused most likely by
      percentages of diesel to lube oil in these two samples different from that in
      spill sample 1460.

PMID- 21956547
TI  - An oxidative cross-dehydrogenative-coupling reaction in water using molecular
      oxygen as the oxidant: vanadium catalyzed indolation of tetrahydroisoquinolines.
AB  - An aerobic oxidative cross-dehydrogenative coupling reaction between sp(3) C-H
      and sp(2) C-H bonds is developed by employing a vanadium catalyst (10 mol%) in an
      aqueous medium using molecular oxygen as the oxidant. This environmentally benign
      strategy exhibits larger substrate scope and shows high regioselectivity.

PMID- 21956548
TI  - Microparticles from apoptotic platelets promote resident macrophage
      differentiation.
AB  - Platelets shed microparticles not only upon activation, but also upon ageing by
      an apoptosis-like process (apoptosis-induced platelet microparticles, PM(ap)).
      While the activation-induced microparticles have widely been studied, not much is
      known about the (patho)physiological consequences of PM(ap) formation. Flow
      cytometry and scanning electron microscopy demonstrated that PM(ap) display
      activated integrins and interact to form microparticle aggregates. PM(ap) were
      chemotactic for monocytic cells, bound to these cells, an furthermore stimulated
      cell adhesion and spreading on a fibronectin surface. After prolonged incubation,
      PM(ap) promoted cell differentiation, but inhibited proliferation. Monocyte
      membrane receptor analysis revealed increased expression levels of CD11b
      (integrin alpha(M)beta(2)), CD14 and CD31 (platelet endothelial cell adhesion
      molecule-1), and the chemokine receptors CCR5 and CXCR4, but not of CCR2. This
      indicated that PM(ap) polarized the cells into resident M2 monocytes. Cells
      treated with PM(ap) actively consumed oxidized low-density lipoprotein (oxLDL),
      and released matrix metalloproteinases and hydrogen peroxide. Further
      confirmation for the differentiation towards resident professional phagocytes
      came from the finding that PM(ap) stimulated the expression of the (ox)LDL
      receptors, CD36 and CD68, and the production of proinflammatory and
      immunomodulating cytokines by monocytes. In conclusion, interaction of PM(ap)
      with monocytic cells has an immunomodulating potential. The apoptotic
      microparticles polarize the cells into a resident M2 subset, and induce
      differentiation to resident professional phagocytes.

PMID- 21956549
TI  - [The palliative treatment plan as basis for informed decisions in palliative or
      emergency care].
AB  - Acute vital crisis in end-of-life situations may result in a person being
      hospitalized and thus, expelled from his intimate environment, which aggravates
      the continuity of care. This entails a heavy burden for patients and necessitates
      an emergency medical services (EMS) call without recognizable benefit in many
      cases. Crisis episodes frequently mark the beginning of the dying process.
      Advance care planning or end-of-life care in elderly patients can help prevent
      such situations and ensure high contentment of patients, families and caregivers.
      Frequently, the question arises whether the burden arising from further
      hospitalization or from certain medical treatment options is reasonably balanced
      by the potential benefits of the steps taken. In such comprehensive care settings
      a custom-tailored palliative treatment plan may serve as an instrument for
      advance care planning. A palliative treatment plan set up by a physician together
      with a caregiver helps ensure that acute problems can be solved quickly and
      satisfactorily in the patient's customary surroundings. If EMS assistance is
      still needed, the emergency physician has written information on the patient's
      situation and can act quickly to meet the patient's immediate needs. This also
      means that EMS personnel must be properly trained in providing palliative care.
      In this way the palliative treatment plan can help caregivers continue to care
      for patients in their intimate surroundings.

PMID- 21956550
TI  - Cardiovascular risk stratification and antihypertensive therapy according to
      guidelines in the outpatient setting.
AB  - BASIC CONCEPTS AND METHODOLOGY: Acceptance of the ESH/ESC 2007 hypertension
      guidelines and their reappraisal 2009 are not known by Austrian practitioners.
      Therefore, within the frame of a noninterventional trial we investigated 3,488
      ambulatory hypertensive patients. Primary goal was the evaluation of the
      assignment to cardiovascular risk categories according to the ESH/ESC charts by
      office-based physicians compared to an independent risk adjudication using the
      same data and method. Further goals were assessment of compliance with the
      recommendation to start combination treatment in grade 2 and 3 hypertension and
      efficacy and tolerability of treatment with candesartan. RESULTS: The comparison
      revealed incorrect physicians' risk assessment for approximately 60% of the
      patients with a strong tendency for underestimation. Despite guidelines
      recommending an initial combination therapy for hypertension >=160/90 mmHg, 15.4%
      of these patients still received candesartan as a monotherapy. Target blood
      pressure <=140/90 mmHg could be well achieved (in 81.6%) with candesartan as
      monotherapy or combined with hydrochlorothiazide (HCTZ) for hypertension grade 1
      3. CONCLUSIONS: Guidelines for assessment of individual risk and derived therapy
      algorithms should be better communicated in the outpatient setting. Candesartan
      alone or combined with HCTZ is an effective and well tolerated therapeutic option
      to control blood pressure in the majority of patients.

PMID- 21956551
TI  - [Diagnosis of osteoporosis in geriatric patients - possibilities and
      limitations].
AB  - Osteoporosis with its increased risk of low-trauma fractures has to be regarded
      as a disorder with significant influence on quality of life, increased morbidity
      and mortality in the elderly. Therapies of osteoporosis, in particular drug
      therapies aiming to reduce the fracture risk, are in general only initiated after
      diagnostic procedures prior to the start of osteoporosis therapy. Consequently,
      diagnosis of osteoporosis plays a key role in optimized patient care and
      management. Medical history, physical examination, planar X-ray,
      osteodensitometry and a range of laboratory parameters make up the key steps in
      the diagnostic work up of osteoporosis. In some clinical settings such as the
      investigation of possible occult fractures after falls, additional imaging
      methods including computed tomography, magnetic resonance imaging, and bone
      scintigraphy may be necessary to make up adequate diagnosis. However, it has to
      be questioned in which way all these diagnostic investigations can be effectively
      used in the diagnostic work up of geriatric patients. The article will give an
      overview of the different diagnostic methods with their possibilities and
      limitations and will present possible diagnostic work flows based on frequent
      clinical settings seen in geriatric patients.

PMID- 21956553
TI  - Preparation of unnatural amino acids with ammonia-lyases and 2,3-aminomutases.
AB  - Ammonia-lyases catalyze a wide range of processes leading to alpha,beta
      unsaturated compounds by elimination of ammonia. In this chapter, ammonia-lyases
      are reviewed with major emphasis on their synthetic applications in
      stereoselective preparation of unnatural amino acids. Besides the synthesis of
      various unnatural alpha-amino acids with the aid of phenylalanine ammonia-lyases
      (PALs) utilizing the 3,5-dihydro-5-methylidene-4H-imidazol-4-one (MIO) prosthetic
      groups, the biotransformations leading to various unnatural beta-amino acids with
      phenylalanine 2,3-aminomutases using the same catalytic MIO prosthetic group are
      discussed. Cloning, production, purification, and biotransformation protocols for
      PAL are described in detail.

PMID- 21956554
TI  - Multistep enzyme catalyzed reactions for unnatural amino acids.
AB  - The use of unnatural amino acids, particularly synthetic alpha-amino acids, for
      modern drug discovery research requires the availability of enantiomerically pure
      isomers. Starting from a racemate, one single enantiomer can be obtained using a
      deracemization process. The two more common strategies of deracemization are
      those obtained by stereoinversion and by dynamic kinetic resolution. Both
      techniques will be here described using as a substrate the D,L-3-(2-naphthyl)
      alanine, a non-natural amino acid: the first one employing a multi-enzymatic
      redox system, the second one combining an hydrolytic enzyme together with a base
      catalyzed substrate racemization. In both cases, the final product, L-3-(2
      naphthyl)alanine, is recovered with good yield and excellent enantiomeric excess.

PMID- 21956555
TI  - Enzymatic production of enantiopure amino acids from mono-substituted hydantoin
      substrates.
AB  - Biocatalytic conversion of 5-substituted hydantoin derivatives is an efficient
      method for the production of unnatural enantiomerically pure amino acids. The
      enzymes required to carry out this hydrolysis occur in a wide variety of
      eubacterial species each of which exhibit variations in substrate selectivity,
      enantiospecificity, and catalytic efficiency. Screening of the natural
      environment for bacterial strains capable of utilizing hydantoin as a nutrient
      source (as opposed to rational protein design of known enzymes) is a cost
      effective and valuable approach for isolating microbial species with novel
      hydantoin-hydrolysing enzyme systems. Once candidate microbial isolates have been
      identified, characterization and optimization of the activity of target enzyme
      systems can be achieved by subjecting the hydantoin-hydrolysing system to
      physicochemical manipulations aimed at the enzymes activity within the natural
      host cells, expressed in a heterologous host, or as purified enzymes. The latter
      two options require knowledge of the genes encoding for the hydantoin-hydrolysing
      enzymes. This chapter describes the methods that can be used in conducting such
      development of hydantoinase-based biocatalytic routes for production of target
      amino acids.

PMID- 21956556
TI  - Preparation of glutamate analogues by enzymatic transamination.
AB  - Aminotransferases are key enzymes of the metabolism of proteinogenic amino acids.
      These ubiquitous biocatalysts show high specific activities and relaxed substrate
      specificities making them valuable tools for the stereoselective synthesis of
      unnatural amino acids. We describe here the application of aspartate
      aminotransferase and branched chain aminotransferase from E. coli for the
      synthesis of various glutamate analogues, molecules of particular interest
      regarding the neuroactive properties of glutamic acid.

PMID- 21956557
TI  - Carbon-carbon bond-forming enzymes for the synthesis of non-natural amino acids.
AB  - An enzymatic methodology for the preparation of beta-hydroxy-alpha-amino acid
      derivatives is described. The method consists of the stereoselective aldol
      addition reaction of glycine to N-Cbz-amino aldehydes furnishing 3-hydroxy-2,4
      diaminobutyric derivatives.

PMID- 21956558
TI  - Engineering cyclic amidases for non-natural amino acid synthesis.
AB  - Hydantoinases/dihydropyrimidinases are important biotechnological enzymes
      involved in the production of alpha- and beta-amino acids. Their isolation from
      new sources with different substrate specificities, improved activity,
      enantioselectivity, or higher stability continues to be of great industrial
      interest. Here, we provide a detailed description of how to produce high
      quantities of the recombinant hydantoinase/dihydropyrimidinase enzyme from
      Sinorhizobium meliloti CECT4114 (SmeDhp). Several techniques are combined to
      obtain this goal, from cloning to activity measurement by HPLC.

PMID- 21956559
TI  - NMR analysis of unnatural amino acids in natural antibiotics.
AB  - A large number of modified amino acids other than the canonical amino acid
      residues can be found in natural products, especially antibiotics. The structure
      of these peptide-based compounds is investigated using modern two-dimensional NMR
      techniques. The automatic assignment of the 2D NMR proton spectra and consequent
      determination of the primary and 3D structure of peptides or small size proteins
      containing natural amino acids is nowadays routine. However, a deficiency in the
      ability to readily sequence peptides containing unnatural amino acids still
      remains and a great human effort and time is required. The experimental methods
      and the protocols of manual analysis of the data are described in the following
      sections.

PMID- 21956560
TI  - Site-specific incorporation of unnatural amino acids as probes for protein
      conformational changes.
AB  - Site-specific in vivo incorporation of unnatural amino acids provides powerful
      tools for the study of protein interaction and dynamics. Here, we provide a
      protocol for the incorporation of six such UAA probes into a GFP reporter system,
      expressed in Escherichia coli from both arabinose and lactose-inducible
      expression plasmids using an autoinduction media.

PMID- 21956561
TI  - Application of unnatural amino acids to the de novo design of selective
      antibiotic peptides.
AB  - Because of their unique mechanism of cytotoxicity against bacteria and other
      microorganisms, antimicrobial peptides have received a great deal of attention as
      possible therapeutic agents. Incorporation of unnatural amino acids into the
      peptide sequences has the potential to improve the organism selectivity and
      potency of these peptides as well as increase their metabolic stability. This
      protocol outlines the logic used to selectively incorporate unnatural amino acid
      into a peptide sequence in an attempt to obtain peptides with increased
      therapeutic potential as antibiotic agents.

PMID- 21956562
TI  - Use of unnatural amino acids to probe structure-activity relationships and mode
      of-action of antimicrobial peptides.
AB  - Endogenous antimicrobial peptides (AMPs) can have multimodal mechanisms of
      bacterial inactivation, such as membrane lysis, interference with cell wall
      biosynthesis or membrane-based protein machineries, or translocation through the
      membrane to intracellular targets. The controlled variation of side-chain
      characteristics in their amino acid residues can provide much useful information
      on structure-activity relationships and mode-of-action, and also lead to improved
      activities. The small size and relatively low complexity of AMPs make them
      amenable to solid-phase peptide synthesis, facilitating the use of
      nonproteinogenic amino acids and vastly increasing the accessible molecular
      diversity of side chains. Here, we describe how such residues can be used to
      modulate such key parameters as cationicity, hydrophobicity, steric factors
      conformational stability, and H-bonding.

PMID- 21956563
TI  - Experimental methods for scanning unnatural amino acid mutagenesis.
AB  - Site-specific incorporation of unnatural amino acids into proteins in vivo relies
      on the genetic reassignment of nonsense or quadruplet codons. Here, we describe a
      general procedure for the random introduction of these codons into open reading
      frames resulting in protein libraries that are scanned with unnatural amino acid
      residues. These libraries can enable large-scale mutagenesis experiments aimed at
      understanding and improving protein function.

PMID- 21956564
TI  - Genetic incorporation of unnatural amino acids into proteins in yeast.
AB  - Unnatural amino acids can be genetically incorporated into proteins in live cells
      by using an orthogonal tRNA/aminoacyl-tRNA synthetase pair. Here we describe a
      method to efficiently express the orthogonal tRNA and synthetase in Saccharomyces
      cerevisiae, which enables unnatural amino acids to be genetically incorporated
      into target proteins in yeast with high efficiency. We also describe the use of a
      yeast strain deficient in the nonsense-mediated mRNA decay, which further
      increases the unnatural amino acid incorporation efficiency when a stop codon is
      used to encode the unnatural amino acid. These strategies will facilitate the
      investigation of proteins and their related biological processes in yeast by
      exploiting the novel properties afforded by unnatural amino acids.

PMID- 21956565
TI  - Site-specific incorporation of unnatural amino acids into proteins in mammalian
      cells.
AB  - Expanding the repertoire of genetically encoded amino acids in cultured mammalian
      cells requires the expression of the bacterial or archaeal pair of a tRNA and an
      aminoacyl-tRNA synthetase variant engineered to be specific to the amino acid,
      along with the supplementation of an unnatural amino acid in the growth medium.
      The expression of the pair is generally achieved by transfecting the cultured
      cells with the plasmids bearing the genes encoding the exogenous pair of
      translation molecules. Here, we provide a description of some of these plasmids
      and protocols for transfecting cells with the plasmids and preparing growth media
      supplemented with unnatural amino acids, to facilitate their incorporation into
      proteins at specific sites.

PMID- 21956566
TI  - Incorporation of unnatural non-alpha-amino acids into the N-terminus of proteins
      in a cell-free translation system.
AB  - Unnatural amino acid mutagenesis allows us to introduce unnatural alpha-amino
      acids into internal positions of proteins in response to expanded codons such as
      amber and four-base codons. To improve the unnatural amino acid mutagenesis, the
      incorporation of unnatural alpha-amino acids and non-alpha-amino acids into the N
      terminus of proteins has been achieved using expanded initiation codons. Here, we
      describe the method for the incorporation of fluorescent-labeled non-alpha-amino
      acids into the N-terminus of proteins in a cell-free translation system.

PMID- 21956567
TI  - Site-specific modification of proteins by the staudinger-phosphite reaction.
AB  - Chemoselective reactions are important tools for the modification of peptides and
      proteins. Thereby the modification is desired to be site specific and
      bioorthogonal. Here we describe the site-specific modification of azido-proteins
      via a Staudinger-type phosphite ligation. The reaction was carried out in aqueous
      system on proteins containing p-azido-phenylalanine in a single position
      introduced by the amber codon technique. A selective introduction of branched
      polyethylene scaffolds can be achieved with the application of the methodology
      reported herein.

PMID- 21956568
TI  - HPLC methods for determination of D-aspartate and N-methyl-D-aspartate.
AB  - D-Amino acids are stereoisomers or optical isomers of naturally occurring L-amino
      acids and thus possess the same chemical structure, but may differ in their
      biological/physiological properties. Until a half century ago, D-amino acids had
      been considered to be unnatural substances found only in microorganisms. However,
      improvements in analytical instruments and methods have revealed that D-amino
      acids are present in invertebrates and vertebrates, including humans, and that
      they possess important physiological functions. D-Aspartate (D-Asp) and its
      methylated form N-methyl-D-aspartate (NMDA) possess neuroendocrine properties in
      many species. Several methods have been developed for determination of D- and L
      enantiomers of amino acids by high performance liquid chromatography (HPLC). We
      report here improved HPLC methods for the specific determination of D-Asp and
      NMDA in biological tissues.

PMID- 21956569
TI  - Estimation of chronological age from the racemization rate of L- and D-aspartic
      acid: how to completely separate enantiomers from dentin.
AB  - Estimation of chronological age is essential in forensic and archeological
      science. The racemization method is one of the best methods to meet the demands
      of these scientific fields, providing both accuracy of the estimated age and
      simplicity of technique. In general, living organs are composed of L-form amino
      acids. Conversion from L-form to D-form amino acids is a first-order chemical
      reaction. Thus, the quantity of D-form amino acids in an organ is proportional to
      the passed time (age) after organ completion if no protein turnover occurs after
      organization. However, every living organ undergoes some degree of protein
      turnover. Therefore, organs with low metabolic rates, such as teeth and bone,
      should be targeted for the racemization method. The most critical point of the
      technique may be the complete separation of D- and L-forms by gas chromatography
      because of the very small amounts of D-form amino acids present. We describe the
      detailed procedures and the critical points for obtaining reliable estimated ages
      using the racemization method.

PMID- 21956570
TI  - Enzymatic detection of D-amino acids.
AB  - D: -Amino acids play several key roles and are widely diffused in living
      organisms, from bacteria (in which D-alanine is a component of the cell wall) to
      mammals (where D-serine is involved in glutamatergic neurotransmission in the
      central nervous system). The study of the biological processes involving D-amino
      acids and their use as clinical or biotechnological biomarkers requires reliable
      methods of quantifying them. Although "traditional" analytical techniques have
      been (and still are) employed for such tasks, enzymatic assays based on enzymes
      which possess a strict stereospecificity (i.e., that are only active on the D
      enantiomers of amino acids) allowed the set-up of low-cost protocols with a high
      sensitivity and selectivity and suitable for determining the D-amino acid content
      of complex biological samples. The most exploited enzyme in these assays is D
      amino acid oxidase, a flavoenzyme that exclusively oxidizes D-amino acids and
      possesses with a broad substrate specificity and a high kinetic efficiency.

PMID- 21956571
TI  - An enzymatic-HPLC assay to monitor endogenous D-serine release from neuronal
      cultures.
AB  - D-Serine is a transmitter-like molecule that physiologically activates NMDA
      receptors in the brain. Although D-serine was thought to be exclusively released
      by astrocytes, we recently demonstrated endogenous D-serine release from neurons
      in cultures and slices. So far high-performance liquid chromatography (HPLC) has
      been the standard technique to monitor D-serine and other amino acids. This
      method employs pre-column derivatization with a chiral reagent to produce
      fluorescence derivatives that can be further separated on a reversed-phase
      column. Due to the close retention times of L-serine, L-glutamine, and D-serine,
      the quantification of low levels of endogenous D-serine synthesis and release
      from cell cultures and tissues can be challenging. We here describe an enzymatic
      treatment method to specifically destroy L-glutamine and L-serine by glutaminase
      and L-serine dehydratase enzymes, respectively, allowing accurate determination
      of nanomolar D: -serine concentrations by subsequent HPLC analysis.

PMID- 21956572
TI  - Electrophysiological analysis of the modulation of NMDA-receptors function by D
      serine and glycine in the central nervous system.
AB  - The NMDA subtypes of glutamatergic receptors (NMDARs) are unusual in that their
      activation requires the binding of both glutamate and a co-agonist glycine or D
      serine. Whereas glycine was first suggested to play such a role, it was later
      established that D-serine could serve as an endogenous co-agonist at different
      central synapses. We still do not know the exact nature of the endogenous co
      agonist(s) of NMDARs and the function of the so-called glycine B site in many
      brain structures. We introduced few years ago the use of enzymes that
      specifically degrade either D-serine or glycine to decipher the influence of
      these amino acids on NMDA receptors function. The use of these enzymatic
      scavengers represents an invaluable technique for neurophysiologists
      investigating the neuromodulation of the glycine B site in the CNS. Here, we
      describe the proper way to manipulate these enzymes during electrophysiological
      recordings in acute brain slices and highlight the experimental tricks.

PMID- 21956573
TI  - Biosensors for D-amino acid detection.
AB  - The presence of D-amino acids in foods is promoted by harsh technological
      processes (e.g., high temperature or extreme pH values) or can be the consequence
      of adulteration or microbial contamination (D-amino acids are major components of
      the bacterial cell wall). For this reason, quality control is becoming more and
      more important both for the industry (as a cost factor) and for consumer
      protection. For routine food analysis and quality control, simple and easily
      applicable analytical methods are needed: biosensors can often satisfy these
      requirements. The use of an enzymatic, stereospecific reaction could confer
      selectivity to a biosensor for detecting and quantifying D-amino acids in
      foodstuffs. The flavoenzyme D-amino acid oxidase from the yeast Rhodotorula
      gracilis is an ideal biocatalyst for this kind of application because of its
      absolute stereospecificity, very high turnover number with various substrates,
      tight binding with the FAD cofactor, and broad substrate specificity.
      Furthermore, alterations in the local brain concentrations of D-serine
      (predominantly D-amino acid in the mammalian central nervous system) have been
      related to several neurological and psychiatric diseases. Therefore, quantifying
      this neuromodulator represents an important task in biological, medical, and
      pharmaceutical research. Recently, an enzymatic microbiosensor, also using R.
      gracilis D-amino acid oxidase as biocatalyst, was developed for detecting D
      serine in vivo.

PMID- 21956574
TI  - Analysis of D-beta-aspartyl isomers at specific sites in proteins.
AB  - Recent studies have shown that biologically uncommon D-beta-aspartic acid
      residues accumulate in specific proteins during the aging process. However,
      aspartyl residues are not racemized uniformly because D-Asp appears to be
      confined to particular sites in these proteins. We here describe the method to
      identify the specific sites of D-beta-aspartic acids inversion in proteins.

PMID- 21956575
TI  - Nutritional value of D-amino acids, D-peptides, and amino acid derivatives in
      mice.
AB  - This paper describes a method for determining the nutritional value of D-amino
      acids, D-peptides, and amino acid derivatives using a growth assay in mice fed a
      synthetic all-amino acid diet. A large number of experiments were carried out in
      which a molar equivalent of the test compound replaced a nutritionally essential
      amino acid such as L-lysine (L-Lys), L-methionine (L-Met), L -phenylalanine (L
      Phe), and L-tryptophan (L-Trp) as well as the semi-essential amino acids L
      cysteine (L-Cys) and L-tyrosine (L-Tyr). The results show wide-ranging variations
      in the biological utilization of test substances. The method is generally
      applicable to the determination of the biological utilization and safety of any
      amino acid derivative as a potential nutritional source of the corresponding L
      amino acid. Because the organism is forced to use the D-amino acid or amino acid
      derivative as the sole source of the essential or semi-essential amino acid being
      replaced, and because a free amino acid diet allows better control of
      composition, the use of all-amino acid for such determinations may be preferable
      to protein-based diets.

PMID- 21956576
TI  - Preparation and assay of recombinant serine racemase.
AB  - Serine racemase is a glial and neuronal enzyme that reversibly converts L-serine
      to D-serine, an endogenous co-agonist of N-methyl-D-aspartate receptor type
      glutamate receptors (NMDARs). Here we present methods to recombinantly express
      and purify serine racemase in bacteria and two complementary ways to determine D
      serine levels in unknown samples. Furthermore, a detailed protocol of serine
      racemase activity assays is described that can be used to screen for activators
      and inhibitors in vitro.

PMID- 21956577
TI  - Assay of amino acid racemases.
AB  - D-Amino acids play important physiological roles in the mammalian body. Recent
      investigations revealed that, in mammals, D-amino acids are synthesized from
      their corresponding L-enantiomers via amino acid racemase. This article describes
      a method used to measure amino acid racemase activity by high-performance liquid
      chromatography (HPLC). The assay involves fluorogenic chiral derivatization of
      amino acids with a newly developed reagent, and enantioseparation of D- and L
      amino acid derivatives by HPLC. The method is accurate and reliable, and can be
      automated using a programmable autosampling injector.

PMID- 21956578
TI  - Assays of D-amino acid oxidases.
AB  - D-Amino acid oxidase and D-aspartate oxidase are two well-known FAD-containing
      flavooxidases that catalyze the same reaction (the oxidative deamination) on
      different D-amino acids. D-aspartate oxidase is specific for acidic D-amino acids
      (i.e., D-aspartate and D-glutamate) and D-amino acid oxidase is active on neutral
      and polar D-amino acids (a low activity is also detected on basic D-amino acids).
      The assay of these flavoenzymes is of utmost importance in different fields
      because D-amino acids are common constituents of bacterial cell walls, are
      present in foods and because free D-serine and D-aspartic acid were identified in
      brain and peripheral tissues of mammals. In this chapter, we report on the most
      used methods employed to assay the activity of D-amino acid oxidase and D
      aspartate oxidase. Interestingly, their activity can be followed using different
      assays, namely D-amino acid or oxygen consumption, alpha-keto acid or ammonia
      production, or using artificial dyes as final indicator of the flavin redox
      reaction.

PMID- 21956579
TI  - Enzymes acting on D-amino acid containing peptides.
AB  - Using a synthetic oligopeptide (D-Phe)(4), a microorganism Bacillus cereus DF4-B
      producing alkaline D-peptidase (ADP) was isolated. The enzymatic properties have
      been characterized; the enzyme showed D-stereospecific dipeptidyl aminopeptidase
      and endopeptidase activities. The enzyme was active toward (D-Phe)(n), Boc-(D
      Phe)(n), (D-Phe)(n) methyl ester, D-Phe-NH(2), Boc-(D-Phe)(n) methyl ester, and
      Boc-(D-Phe)(n) tert-butyl ester, but not toward (D-Ala)(n) (n = 2-4), (D-Val)(3),
      and (D-Leu)(2).

PMID- 21956580
TI  - Monitoring of breathing phases using  a bioacoustic method in healthy awake
      subjects.
AB  - OBJECTIVE: To test the ability of a microphone recording system, located distal
      to the respiratory outflow tract, to track the timing of the inspiratory and
      expiratory phases of breathing in awake healthy subjects. METHODS: Fifteen
      subjects participated. Breath sounds were recorded using a microphone embedded in
      a face frame in a fixed location in relation to the nostrils and mouth, while
      simultaneously recording respiratory movements by respiratory inductance
      plethysmography (RIP). Subjects were studied while supine and were instructed to
      breathe normally for 2 min: through their noses only (nasal breathing), during
      the first min, and through their mouths only (oral breathing) during the second
      min. Five subjects (test group) were chosen randomly to extract features from
      their acoustic data. Ten breaths (5 nasal and 5 oral breaths) from each subject
      were studied. Inspiratory and expiratory segments of breath sounds were
      determined and extracted from the acoustic data by comparing it to the RIP trace.
      Subsequently, the frequency spectrum of each phase was then determined. Spectral
      variables derived from the 5 test subjects were applied prospectively to detect
      breathing phases in the remaining 10 subjects (validation group). RESULTS: Test
      group data showed that the mean of all inspiratory spectra peaked between 30 and
      270 Hz, flattened between 300 and 1,100 Hz, and peaked again with a center
      frequency of 1,400 Hz. The expiratory spectra peaked between 30 and 180 Hz and
      its power dropped off exponentially after that. Accordingly, the bands ratio (BR)
      of frequency magnitudes between 500 and 2500 Hz to frequency magnitudes between 0
      and 500 Hz was chosen as a feature to distinguish between breathing phases. BR
      for the mean inspiratory spectrum was 2.27 and for the mean expiratory spectrum
      was 0.15. The route of breathing did not affect the BR ratio within the same
      phase. When this BR was applied to 436 breathing phases in the validation group,
      424 (97%) were correctly identified (Kappa = 0.96, P < 0.001) indicating strong
      agreement between the acoustic method and the RIP. CONCLUSION: Frequency spectra
      of breathing sounds recorded from a face-frame, reliably identified the
      inspiratory and expiratory phases of breathing. This technique may have various
      applications for respiratory monitoring and analysis.

PMID- 21956581
TI  - Synthesis of new pyrroles of potential anti-inflammatory activity.
AB  - We herein disclose a series of novel pyrrole derivatives 1-4 and pyrrolo[2,3
      d]pyrimidine derivatives 6-11 as novel potent anti-inflammatory compounds. The
      structures were confirmed by IR, (1) H-NMR, and MS. Some newly synthesized
      compounds were examined for their in-vivo anti-inflammatory activity. Several
      derivatives showed a promising anti-inflammatory activity compared to ibuprofen.
      In this paper, we examine and discuss the structure-activity relationships and
      anti-inflammatory activities of these compounds.

PMID- 21956582
TI  - Herbal remedies: science or tradition? The ethical dilemma.

PMID- 21956583
TI  - High-performance organic single-crystal field-effect transistors of indolo[3,2
      b]carbazole and their potential applications in gas controlled organic memory
      devices.

PMID- 21956585
TI  - Effect of laser welding on the titanium ceramic tensile bond strength.
AB  - Titanium reacts strongly with elements, mainly oxygen at high temperature. The
      high temperature of titanium laser welding modifies the surface, and may
      interfere on the metal-ceramic tensile bond strength. OBJECTIVE: The influence of
      laser welding on the titanium-ceramic bonding has not yet been established. The
      purpose of this in vitro study was to analyze the influence of laser welding
      applied to commercially pure titanium (CpTi) substructure on the bond strength of
      commercial ceramic. The influence of airborne particle abrasion (Al2O3)
      conditions was also studied. MATERIAL AND METHODS: Forty CpTi cylindrical rods (3
      mm x 60 mm) were cast and divided into 2 groups: with laser welding (L) and
      without laser welding (WL). Each group was divided in 4 subgroups, according to
      the size of the particles used in airborne particle abrasion: A - Al2O3 (250 um);
      B - Al2O3 (180 um); C - Al2O3 (110 um); D - Al2O3 (50 um). Ceramic rings were
      fused around the CpTi rods. Specimens were invested and their tensile strength
      was measured at fracture with a universal testing machine at a crosshead speed of
      2.0 mm/min and 200 kgf load cell. Statistical analysis was carried out with
      analysis of variance and compared using the independent t test (p<0.05). RESULTS:
      Significant differences were found among all subgroups (p<0.05). The highest and
      the lowest bond strength means were recorded in subgroups WLC (52.62 MPa) and LD
      (24.02 MPa), respectively. CONCLUSION: Airborne particle abrasion yielded
      significantly lower bond strength as the Al2O3 particle size decreased.
      Mechanical retention decreased in the laser-welded specimens, i.e. the metal
      ceramic tensile bond strength was lower.

PMID- 21956584
TI  - Brain development in the yellow fever mosquito Aedes aegypti: a comparative
      immunocytochemical analysis using cross-reacting antibodies from Drosophila
      melanogaster.
AB  - Considerable effort has been directed towards understanding the organization and
      function of peripheral and central nervous system of disease vector mosquitoes
      such as Aedes aegypti. To date, all of these investigations have been carried out
      on adults but none of the studies addressed the development of the nervous system
      during the larval and pupal stages in mosquitoes. Here, we first screen a set of
      30 antibodies, which have been used to study brain development in Drosophila, and
      identify 13 of them cross-reacting and labeling epitopes in the developing brain
      of Aedes. We then use the identified antibodies in immunolabeling studies to
      characterize general neuroanatomical features of the developing brain and compare
      them with the well-studied model system, Drosophila melanogaster, in larval,
      pupal, and adult stages. Furthermore, we use immunolabeling to document the
      development of specific components of the Aedes brain, namely the optic lobes,
      the subesophageal neuropil, and serotonergic system of the subesophageal neuropil
      in more detail. Our study reveals prominent differences in the developing brain
      in the larval stage as compared to the pupal (and adult) stage of Aedes. The
      results also uncover interesting similarities and marked differences in brain
      development of Aedes as compared to Drosophila. Taken together, this
      investigation forms the basis for future cellular and molecular investigations of
      brain development in this important disease vector.

PMID- 21956586
TI  - Effect of leaching residual methyl methacrylate concentrations on in vitro
      cytotoxicity of heat polymerized denture base acrylic resin processed with
      different polymerization cycles.
AB  - OBJECTIVES: Residual methyl methacrylate (MMA) may leach from the acrylic resin
      denture bases and have adverse effects on the oral mucosa. This in vitro study
      evaluated and correlated the effect of the leaching residual MMA concentrations
      ([MMA]r) on in vitro cytotoxicity of L-929 fibroblasts. MATERIAL AND METHODS: A
      total of 144 heat-polymerized acrylic resin specimens were fabricated using 4
      different polymerization cycles: (1) at 74oC for 9 h, (2) at 74oC for 9 h and
      terminal boiling (at 100oC) for 30 min, (3) at 74oC for 9 h and terminal boiling
      for 3 h, (4) at 74oC for 30 min and terminal boiling for 30 min. Specimens were
      eluted in a complete cell culture medium at 37oC for 1, 2, 5 and 7 days. [MMA]r
      in eluates was measured using high-performance liquid chromatography. In vitro
      cytotoxicity of eluates on L-929 fibroblasts was evaluated by means of cell
      proliferation using a tetrazolium salt XTT (sodium 3'-[1-phenyl-aminocarbonyl)
      3,4-tetrazolium]bis(4-methoxy-6-nitro)benzenesulphonic acid) assay. Differences
      in [MMA]r of eluates and cell proliferation values between polymerization cycles
      were statistically analyzed by Kruskal-Wallis, Friedman and Dunn's multiple
      comparison tests. The correlation between [MMA]r of eluates and cell
      proliferation was analyzed by Pearson's correlation test (p<0.05). RESULTS:
      [MMA]r was significantly (p<0.001) higher in eluates of specimens polymerized
      with cycle without terminal boiling after elution of 1 and 2 days. Cell
      proliferation values for all cycles were significantly (p<0.01) lower in eluates
      of 1 day than those of 2 days. The correlation between [MMA]r and cell
      proliferation values was negative after all elution periods, showing significance
      (p<0.05) for elution of 1 and 2 days. MMA continued to leach from acrylic resin
      throughout 7 days and leaching concentrations markedly reduced after elution of 1
      and 2 days. CONCLUSION: Due to reduction of leaching residual MMA concentrations,
      use of terminal boiling in the polymerization process for at least 30 min and
      water storage of the heat-polymerized denture bases for at least 1 to 2 days
      before denture delivery is clinically recommended for minimizing the residual MMA
      and possible cytotoxic effects.

PMID- 21956587
TI  - Are torque values of preadjusted brackets precise?
AB  - OBJECTIVE: The aim of the present study was to verify the torque precision of
      metallic brackets with MBT prescription using the canine brackets as the
      representative sample of six commercial brands. MATERIAL AND METHODS: Twenty
      maxillary and 20 mandibular canine brackets of one of the following commercial
      brands were selected: 3M Unitek, Abzil, American Orthodontics, TP Orthodontics,
      Morelli and Ortho Organizers. The torque angle, established by reference points
      and lines, was measured by an operator using an optical microscope coupled to a
      computer. The values were compared to those established by the MBT prescription.
      RESULTS: The results showed that for the maxillary canine brackets, only the
      Morelli torque (-3.33o) presented statistically significant difference from the
      proposed values (-7o). For the mandibular canines, American Orthodontics (-6.34o)
      and Ortho Organizers (-6.25o) presented statistically significant differences
      from the standards (-6o). Comparing the brands, Morelli presented statistically
      significant differences in comparison with all the other brands for maxillary
      canine brackets. For the mandibular canine brackets, there was no statistically
      significant difference between the brands. CONCLUSIONS: There are significant
      variations in torque values of some of the brackets assessed, which would
      clinically compromise the buccolingual positioning of the tooth at the end of
      orthodontic treatment.

PMID- 21956589
TI  - Methanesulfonates of high-valent metals: syntheses and structural features of
      MoO2(CH3SO3)2, UO2(CH3SO3)2, ReO3(CH3SO3), VO(CH3SO3)2, and V2O3(CH3SO3)4 and
      their thermal decomposition under N2 and O2 atmosphere.
AB  - Oxide methanesulfonates of Mo, U, Re, and V have been prepared by reaction of
      MoO(3), UO(2)(CH(3)COO)(2).2H(2)O, Re(2)O(7)(H(2)O)(2), and V(2)O(5) with
      CH(3)SO(3)H or mixtures thereof with its anhydride. These compounds are the first
      examples of solvent-free oxide methanesulfonates of these elements.
      MoO(2)(CH(3)SO(3))(2) (Pbca, a=1487.05(4), b=752.55(2), c=1549.61(5) pm,
      V=1.73414(9) nm(3), Z=8) contains [MoO(2)] moieties connected by [CH(3)SO(3)]
      ions to form layers parallel to (100). UO(2)(CH(3)SO(3))(2) (P2(1)/c,
      a=1320.4(1), b=1014.41(6), c=1533.7(1) pm, beta=112.80(1) degrees , V=1.8937(3)
      nm(3), Z=8) consists of linear UO(2)(2+) ions coordinated by five [CH(3)SO(3)]
      ions, forming a layer structure. VO(CH(3)SO(3))(2) (P2(1)/c, a=1136.5(1),
      b=869.87(7), c=915.5(1) pm, beta=113.66(1) degrees , V=0.8290(2) nm(3), Z=4)
      contains [VO] units connected by methanesulfonate anions to form corrugated
      layers parallel to (100). In ReO(3)(CH(3)SO(3)) (P1, a=574.0(1), b=1279.6(3),
      c=1641.9(3) pm, alpha=102.08(2), beta=96.11(2), gamma=99.04(2) degrees ,
      V=1.1523(4) nm(3), Z=8) a chain structure exhibiting infinite O-[ReO(2)]-O
      [ReO(2)]-O chains is formed. Each [ReO(2)]-O-[ReO(2)] unit is coordinated by two
      bidentate [CH(3)SO(3)] ions. V(2)O(3)(CH(3)SO(3))(4) (I2/a, a=1645.2(3),
      b=583.1(1), c=1670.2(3) pm, beta=102.58(3), V=1.5637(5) pm(3), Z=4) adopts a
      chain structure, too, but contains discrete [VO]-O-[VO] moieties, each
      coordinated by two bidentate [CH(3)SO(3)] ligands. Additional methanesulfonate
      ions connect the [V(2)O(3)] groups along [001]. Thermal decomposition of the
      compounds was monitored under N(2) and O(2) atmosphere by
      thermogravimetric/differential thermal analysis and XRD measurements. Under N(2)
      the decomposition proceeds with reduction of the metal leading to the oxides
      MoO(2), U(3)O(7), V(4)O(7), and VO(2); for MoO(2)(CH(3)SO(3))(2), a small amount
      of MoS(2) is formed. If the thermal decomposition is carried out in a atmosphere
      of O(2) the oxides MoO(3) and V(2)O(5) are formed.

PMID- 21956588
TI  - Effect of propolis gel on the in vitro reduction of dentin permeability.
AB  - OBJECTIVE: The aim of this study was to evaluate the capacity of potassium
      oxalate, fluoride gel and two kinds of propolis gel to reduce the hydraulic
      conductance of dentin, in vitro. MATERIAL AND METHODS: The methodology used for
      the measurement of hydraulic conductance of dentin in the present study was based
      on a model proposed in literature. Thirty-six 1-mm-thick dentin discs, obtained
      from extracted human third molars were divided into 4 groups (n=9). The groups
      corresponded to the following experimental materials: GI-10% propolis gel, pH
      4.1; GII-30% propolis gel; GIII-3% potassium oxalate gel, pH 4,1; and GIV-1.23%
      fluoride gel, pH 4.1, applied to the dentin under the following surface
      conditions: after 37% phosphoric acid and before 6% citric acid application. The
      occluding capacity of the dentin tubules was evaluated using scanning electron
      microscopy (SEM) at *500, *1,000 and *2,000 magnifications. Data were analyzed
      statistically by two-way ANOVA and Tukey's test at 5% significance level.
      RESULTS: Groups I, II, III, IV did not differ significantly from the others in
      any conditions by reducing in hydraulic conductance. The active agents reduced
      dentin permeability; however they produced the smallest reduction in hydraulic
      conductance when compared to the presence of smear layer (P<0.05). The
      effectiveness in reducing dentin permeability did not differ significantly from
      10% or 30% propolis gels. SEM micrographs revealed that dentin tubules were
      partially occluded after treatment with propolis. CONCLUSIONS: Under the
      conditions of this study, the application of 10% and 30% propolis gels did not
      seem to reduce the hydraulic conductance of dentin in vitro, but it showed
      capacity of partially obliterating the dentin tubules. Propolis is used in the
      treatment of different oral problems without causing significant great collateral
      effects, and can be a good option in the treatment of patients with dentin
      sensitivity.

PMID- 21956590
TI  - Hepatitis B virus X protein mutant upregulates CENP-A expression in hepatoma
      cells.
AB  - The carcinogenic role of hepatitis B virus x protein (HBx) in hepatocellular
      carcinoma (HCC) remains largely unknown. Centromere protein A (CENP-A) has been
      found to be frequently overexpressed in HCC. In the present study, we aimed to
      investigate the role of HBx in regulating CENP-A activity in HCC carcinogenesis.
      CENP-A expression was examined and the HBx gene was sequenced in 20 HBsAg
      positive HCC patients and corresponding non-cancerous liver tissues. The
      influence of HBx mutants on CENP-A expression in HepG2 cells was analyzed by a
      series of assays. We found that CENP-A expression was significantly elevated in
      HCC tissues. HBx deletion, especially the COOH-terminal deletion of HBx is a
      frequent event in HBV-associated HCC tissues. A positive correlation was found
      between CENP-A expression and HBx COOH mutation in HCC tissues. HBx mutant
      increased the expression of the CENP-A mRNA and protein compared with full-length
      HBx. However, HBx did not directly interact with CENP-A. It is concluded that
      overexpression of CENP-A is closely associated with HBx COOH mutation in HCC. HBx
      mutant can increase CENP-A expression, probably through a mechanism independent
      of their physical combination, and thereby it may represent a potential
      therapeutic strategy for HCC.

PMID- 21956592
TI  - Folate metabolism-related gene polymorphisms and susceptibility to primary liver
      cancer in North China.
AB  - Genetic factors may contribute to individual differences in cancer
      susceptibility. This study was designed to investigate the effects of the
      polymorphisms of methylenetetrahydrofolate reductase 677 C -> T (MTHFR 677 C ->
      T), methylenetetrahydrofolate reductase 1298 A -> C (MTHFR 1298A -> C),
      thymidylate synthase (TYMS 3R -> 2R), and methionine synthase 2756 A -> G (MTR
      2756 A -> G) on the risk of primary liver cancer (PLC). We conducted a case
      control study involving 356 PLC cases and 641 healthy controls in North China.
      Compared with the MTHFR 677CC genotype, the MTHFR 677TT genotype showed an
      increased risk for PLC (TT vs. CC: adjusted odds ratio (OR) = 1.56; 95%
      confidence interval (CI): 1.02-2.40; P = 0.043) after adjusting for gender and
      age, whereas the MTHFR 1298CC genotype showed a significantly decreased risk for
      PLC (CC vs. AA: adjusted OR = 0.23; 95% CI: 0.08-0.70; P = 0.010). However, no
      significant association was found between the TYMS 3R -> 2R or the MTR 2756 A ->
      G polymorphism and the risk of PLC. Our results suggest that the MTHFR 677 C -> T
      and the MTHFR 1298A -> C genetic polymorphisms might play important role in
      hepatic carcinogenesis. Further studies with larger sample sizes are required to
      validate this association.

PMID- 21956593
TI  - More is not always better.

PMID- 21956594
TI  - The best therapy for pilonidal disease: which management for which type?

PMID- 21956595
TI  - Ab initio molecular dynamics approach to tunneling splitting in polyatomic
      molecules.
AB  - An ab initio molecular dynamics approach is combined with the semiclassical
      tunneling method of Makri and Miller, which is applied to estimations of
      tunneling splitting in the umbrella inversion of ammonia and the intramolecular
      hydrogen transfer in malonaldehyde. In the application to malonaldehyde, effects
      of multidimensionality are examined by assigning quantum zero-point energies only
      to significant vibrational modes and changing the amount of energy given to other
      degrees of freedom. The calculated tunneling splitting values are in good
      agreement with the corresponding experimental values for both molecules.

PMID- 21956596
TI  - Rapidly increasing rates of hip fracture in Beijing, China.
AB  - The age-specific rates of hip fractures have been declining in most countries in
      the West but a few studies suggest that the rates might be increasing in areas of
      Asia that are undergoing urbanization. We previously conducted a population-based
      study of hip fracture rates in Beijing, China, in 1990 to 1992 that included
      validation of hip fracture cases. Using a similar approach to validate cases, we
      estimated the age-specific hip fracture rates in Beijing, China, for 2002 to
      2006. Specifically, we obtained hospital discharge data for hip fractures that
      were reported to the Beijing Bureau of Public Health. To confirm the diagnoses,
      Beijing residence, and find cases missed by the public records we checked
      individual cases in the public health records against medical records in a random
      sample of Beijing hospitals. The rates from public health data were adjusted for
      these under- and overestimations. We found that between 1990 and 1992 and 2002
      and 2006, the adjusted age-specific rates of hip fracture over age 50 years
      increased 2.76-fold (95% confidence interval [CI], 2.68-2.84) in women and 1.61
      fold (95% CI, 1.56-1.66) in men. Over age 70 years, the age-specific rates
      increased 3.37-fold (95% CI, 3.28-3.47) in women and 2.01-fold (95% CI, 1.95
      2.07) in men. From 2002 to 2006, the rates over age 50 years increased 58% in
      women and 49% in men. We conclude that the rate of hip fracture has been rising
      very rapidly in Beijing, China. Therefore, the burden of hip fractures may be
      shifting rapidly from the West to urbanizing areas of the East.

PMID- 21956597
TI  - New data on the motion of the normal and reconstructed tympanic membrane.
AB  - HYPOTHESIS: The sound-induced motion of the tympanic membrane has features that
      are most consistent with modal responses to a uniform stimulus. BACKGROUND:
      Conceptual models of the coupling of tympanic membrane motion to the ossicular
      chain can be classified as either modal responses to a uniform stimulation of the
      entire membrane or traveling wave models in which sound energy is captured at the
      membrane's rim and travels along the surface to the umbo. The stroboscopic
      holography technique we use can separate strongly modal or traveling wave
      dominated motions of the tympanic membrane surface. METHODS: We use computer
      aided optoelectronic holography with stroboscopic illumination to measure the
      magnitude and phase of the sound-induced motion of more than 40,000 points on the
      surface of the tympanic membrane in cadaveric human temporal bones. Our
      techniques are sensitive to motions of the membrane as small as 0.01 um and allow
      determinations of membrane displacement at frequencies as large as 20 kHz.
      RESULTS: We report clear signs of both modal tympanic membrane responses and
      traveling waves on the human tympanic membrane. Modal responses are seen
      throughout the frequency range, whereas the traveling waves are most apparent
      between 2 and 8 kHz. In general, the magnitudes of the traveling waves are small
      compared with the modal magnitudes. CONCLUSION: Much of the motion of the
      tympanic membrane is well approximated by modal motions of the tympanic membrane
      surface. This conclusion has implications for eardrum pathology and its
      treatment.

PMID- 21956598
TI  - Lumbar subarachnoid drainage in cerebrospinal fluid leaks after lateral skull
      base surgery.
AB  - OBJECTIVE: To determine the efficacy of lumbar drainage in managing cerebrospinal
      fluid (CSF) leak after lateral skull base surgery. STUDY DESIGN: Retrospective
      case review. SETTING: Academic tertiary referral center. PATIENTS: Patients who
      had a lumbar subarachnoid drain placed after a lateral skull base procedure
      between July 1999 and February 2010 were included. INTERVENTIONS: Patients were
      identified by searching medical records for lateral skull base approach Current
      Procedural Terminology codes. The following variables were recorded for each
      subject: diagnosis, type of lateral skull base operation, duration of lumbar
      drainage, need for revision surgery, and presence of meningitis. MAIN OUTCOME
      MEASURE: Successful cessation of postoperative CSF leakage. RESULTS: Five hundred
      eight charts were reviewed, and 63 patients were identified who received a lumbar
      drain after a lateral skull base operation. The most common diagnosis was
      acoustic neuroma in 61.9%. The most common skull base approaches were the
      translabyrinthine, middle fossa, and transpetrosal approaches. Approximately
      60.3% of patients had CSF rhinorrhea, 23.8% had an incisional leak, and 14.3% had
      otorrhea. The mean duration of lumbar drainage was 4.6 days. Forty eight (76.2%)
      study subjects had resolution of their CSF leak with lumbar drainage. Fifteen
      patients (23.8%) required revision surgery to stop the CSF leak. Lumbar drainage
      was successful in 90% of leaks after the translabyrinthine approach but in only
      50% of those undergoing a suboccipital approach, which was a statistically
      significant difference. CONCLUSION: Postoperative CSF leaks after lateral skull
      base surgery can be managed with a lumbar subarachnoid drain in a majority of
      cases but is more successful after the translabyrinthine than the suboccipital
      approach. Recurrent CSF leaks after lumbar drainage is likely to require a
      revision operation.

PMID- 21956599
TI  - Bilateral simultaneous caloric test for superior semicircular canal evaluation.
AB  - OBJECTIVE: To verify if the superior semicircular canal (SCC) can be stimulated
      using the modified "bilateral simultaneous caloric test" (BSCT). STUDY DESIGN:
      Prospective study in a tertiary care center. METHODS: We performed a simultaneous
      irrigation of both ears with cold water at 24 degrees C. Simultaneous irrigation
      of both ears inhibits the response of the horizontal SSC and avoids vegetative
      reaction. Modified BSCT was completed on 12 healthy individuals with no previous
      otologic history and on 12 patients with unilateral superior SCC obliteration for
      dehiscence syndrome using a middle fossa approach. Caloric response was recorded
      in 3 different positions (midline, head rotated to the right and then rotated to
      the left), and results were compared. RESULTS: Nystagmus was vertical and
      upbeating. In the healthy population, the median intensity of nystagmus was 14.42
      +/- 7.32, 11, and 10.5 degrees per second for the 3 head positions. In the
      population with one obliterated superior SCC, the median intensity of nystagmus
      was 7.58 +/- 3.8 degrees per second when the head was in the midline position,
      6.0 degrees per second when the healthy superior SCC was stimulated, and 1.5
      degrees per second when the obliterated canal was stimulated. Using a
      nonparametric statistical test, the mean intensity difference was statistically
      significant between the 2 populations (p < 0.001) and statistically significant
      between the obliterated and nonobliterated canals (p = 0.003). CONCLUSION: This
      study shows that the superior SCC can be specifically stimulated in humans.
      Modified BSCT can stimulate the superior canal and can provide a good estimation
      of its stimulation intensity after the surgery.

PMID- 21956600
TI  - Influence of DFNB1 status on expressive language in deaf children with cochlear
      implants.
AB  - OBJECTIVE: The objective of this study was to compare the language growth of
      children with connexin-related deafness (DFNB1) who received cochlear implants
      versus the language growth of implanted children with non-DFNB1 deafness. STUDY
      DESIGN: A prospective longitudinal observational study and analysis. SETTING: Two
      tertiary referral centers. PATIENTS: There were 37 children with severe-to
      profound hearing loss who received cochlear implants before the age of 5 years.
      INTERVENTIONS: A standardized language measure, the section for expressive
      language of the Reynell Developmental Language Scale was used to assess
      expressive language skills at 2 times postimplantation (14 and 57 mo
      postimplantation). Molecular screening for DFNB1 gene variants. MAIN OUTCOME
      MEASURES: Language quotient (LQ) scores (i.e., age-equivalent score obtained on
      the Reynell Developmental Language Scale divided by the child's chronological
      age), results of genotyping. RESULTS: The mean language age at the second time
      interval (mean +/- standard deviation, 51.8 +/- 13 mo) was greater than at the
      first testing session (mean +/- standard deviation, 19 +/- 8 mo, p < 0.001,
      Wilcoxon signed rank test). When divided by genotype, DFNB1 children exhibited a
      higher LQ and less variability in scores than non-DFNB1 children at the second
      testing interval (Wilcoxon sign rank test, p = 0.0034). A regression analysis
      (linear-fit by least squares) conducted on 26 children with preimplantation
      audiometric data showed that DFNB1 status was the independent variable with
      greater predictive effect on LQ at the second testing interval, followed by age
      at implantation (R2 = 0.35, p = 0.0479). CONCLUSION: Deaf children who received
      cochlear implants before the age of 5 years and use oral communication show
      substantial improvement in language abilities. In this study, DFNB1 children who
      use cochlear implants show greater gains in expressive language than non-DFNB1
      children, independent of residual hearing, age at implantation, and duration of
      implant use.

PMID- 21956601
TI  - An incidental middle-ear mass: Jacobson's nerve schwannoma.

PMID- 21956603
TI  - Optically trapped microsensors for microfluidic temperature measurement by
      fluorescence lifetime imaging microscopy.
AB  - The novel combination of optical tweezers and fluorescence lifetime imaging
      microscopy (FLIM) has been used, in conjunction with specially developed
      temperature-sensitive fluorescent microprobes, for the non-invasive measurement
      of temperature in a microfluidic device. This approach retains the capability of
      FLIM to deliver quantitative mapping of microfluidic temperature without the
      disadvantageous need to introduce a fluorescent dye that pervades the entire
      micofluidic system. This is achieved by encapsulating the temperature-sensitive
      Rhodamine B fluorophore within a microdroplet which can be held and manipulated
      in the microfluidic flow using optical tweezers. The microdroplet is a double
      bubble in which an aqueous droplet of the fluorescent dye is surrounded by an oil
      shell which serves both to contain the fluorophore and to provide the refractive
      index differential required for optical trapping of the droplet in an external
      aqueous medium.

PMID- 21956602
TI  - Impairments of the medial olivocochlear system increase the risk of noise-induced
      auditory neuropathy in laboratory mice.
AB  - HYPOTHESIS: Impairments of the medial olivocochlear system (MOCS) increase the
      risk of environmentally induced auditory neuropathy spectrum disorder (ANSD).
      BACKGROUND: ANSD is a problem in the neural transmission of auditory information
      that accounts for 10% to 15% of the cases of pediatric hearing loss. The
      underlying mechanisms of the disorder remain poorly understood, but noise
      exposure is an important risk factor. The goal of this study was to identify
      environmental conditions and genetic predispositions that lead to ANSD. Our
      approach was based on the assumption that noise induces ANSD by impeding the
      functional maturation of the brain's sound coding pathways. Because the MOCS
      adjusts the sensitivity of the inner ear to noise, impairments of this feedback
      are predicted to increase the disruptive effects of environmental exposures.
      METHODS: An animal model of ANSD was created by rearing mice in noise. MOCS
      protection was assessed by comparing the incidence of noise-induced ANSD among
      knockout mice lacking feedback and wild-type (WT) controls. The mice were
      screened for ANSD with distortion product otoacoustic emissions, auditory
      brainstem responses, and behavioral measures of gap detection. Single-unit
      recording procedures were used to link these deficits to impaired synaptic
      transmission in the ventral cochlear nucleus. RESULTS: ANSD manifested in noise
      reared mice as intact distortion product otoacoustic emissions, abnormal auditory
      brainstem responses, and impaired gap detection. The phenotype was not observed
      among quiet-reared WT mice but was occasionally noted among noise-reared WT mice.
      The incidence of ANSD significantly increased among knockout mice, especially
      when they were reared in noise. CONCLUSION: Noise promotes ANSD by altering the
      functional maturation of the brain's temporal pathways. Noise-induced impairments
      are reduced by the sound-attenuating effects of the MOCS. Noise levels do not
      need to be unnaturally loud to constitute significant risk in MOCS-compromised
      individuals.

PMID- 21956604
TI  - Dabigatran etexilate in atrial fibrillation patients with severe renal
      impairment: dose identification using pharmacokinetic modeling and simulation.
AB  - Dabigatran, administered orally as the prodrug dabigatran etexilate (DE), is a
      direct thrombin inhibitor shown to be effective in the prevention of stroke and
      systemic embolism in patients with atrial fibrillation (AF). The aim of this
      analysis was to derive a modeling and simulation-based dose and dosing regimen
      for AF patients with severe renal failure who could potentially benefit from the
      use of DE. The exposure was simulated for AF patients with severe renal
      impairment for several combinations of doses (75, 110, 150 mg) and posologies
      (BID, QD, Q2D). Simulations were based on a population pharmacokinetic model
      derived from data from 9522 patients from the pivotal phase III study (RE-LY).
      Atrial fibrillation patients with a creatinine clearance (CRCL) of <30 to >=15
      mL/min treated with a dose of 75 mg DE BID have target plasma level and exposure
      data largely within the concentration range proven to be safe and effective in AF
      patients with CRCL >30 mL/min receiving 150 mg BID. This dosing algorithm was
      also confirmed and supported by the United States Food and Drug Administration
      Clinical Pharmacology Division using their model based on the data from the
      dedicated renal impairment study and taking into account the safety and efficacy
      information from RE-LY.

PMID- 21956605
TI  - Clinical pharmacology basis of deriving dosing recommendations for dabigatran in
      patients with severe renal impairment.
AB  - The objective of this work was to derive a dosing regimen for dabigatran in
      patients with severe renal impairment by modeling and simulation. Data from a
      dedicated renal impairment study were used to model the pharmacokinetics of
      dabigatran in normal and renal-impaired subjects. Model parameters were used to
      simulate the average concentration time-course of dabigatran following various
      dosing regimens. Pharmacokinetics of dabigatran in normal and renal-impaired
      subjects were best described by a 2-compartment open model with first-order
      absorption and elimination. Simulations were performed to select an appropriate
      regimen that reasonably matched the exposures on an average with those observed
      in subjects with moderate renal impairment who did not require a dose adjustment
      because of a favorable benefit-risk. Dabigatran 150 mg given once daily resulted
      in 35% higher average C(max, ss), whereas a 75 mg once daily regimen resulted in
      42% lower average Ctau, relative to that observed with 150 mg administered twice
      daily in subjects with moderate renal impairment. A twice daily regimen of
      dabigatran 75 mg resulted in a reasonable matching of exposures and was selected
      as an appropriate dosing regimen in patients with severe renal impairment. This
      recommendation was incorporated in the dosing and recommendation section of
      dabigatran product insert.

PMID- 21956606
TI  - Delayed cross-reactivity between cyclophosphamide and chlorambucil.

PMID- 21956607
TI  - Impact of sildenafil on survival of patients with idiopathic pulmonary arterial
      hypertension.
AB  - It has been reported that short-term sildenafil therapy is safe and effective for
      patients with pulmonary arterial hypertension. However, data regarding the impact
      of sildenafil on the survival of patients with idiopathic pulmonary arterial
      hypertension remain limited. The study was conducted on 77 patients with newly
      diagnosed idiopathic pulmonary arterial hypertension at Fu Wai Hospital between
      September 2005 and September 2009. Patients were divided into 2 groups: the
      sildenafil group and the conventional group. Nine patients treated with
      sildenafil were re-evaluated by right heart catheterization after 3 months. Our
      data demonstrated that the 6-minute walk distance, World Health Organization
      functional class, mixed venous oxygen saturation, and hemodynamics significantly
      improved after 3 months of sildenafil therapy (P < .05). The baseline
      characteristics of the sildenafil group were similar to those of the conventional
      group. The 1-, 2-, and 3-year survival rates in the sildenafil group were 88%,
      72%, and 68% compared with 61%, 36%, and 27% in the conventional group (P <
      .001). The absence of sildenafil therapy, lower body mass index, and lower mixed
      venous oxygen saturation were found to be independent predictors of mortality. In
      conclusion, sildenafil therapy was found to be associated with improved survival
      in patients with idiopathic pulmonary arterial hypertension.

PMID- 21956608
TI  - Hypothermia associated with antipsychotic drug use: a clinical case series and
      review of current literature.
AB  - Hypothermia as an adverse reaction of antipsychotic drug use represents a
      potentially life-threatening complication. However, the mechanisms by which
      antipsychotic drugs alter thermoregulatory processes in the human body are far
      from being fully understood. Here we present a case series of 5 patients
      developing severe hypothermia after administration of olanzapine and benperidol.
      Controlled by a network of neural structures, body temperature is physiologically
      regulated in far more narrow boundaries than are other vital functions, and its
      homeostasis is critical for survival. The preoptic region in the ventral
      hypothalamus is assumed to act as a coordinating center that is endowed with
      thermosensory units that constantly compare actual body temperature with target
      values and initiate regulatory and compensatory mechanisms in case of mismatch.
      Hypothermia risk seems to increase in the first days after initiation of
      antipsychotic drug therapy or increases in the daily dose. Schizophrenic patients
      bear a higher risk than nonschizophrenic patients treated with antipsychotic
      drugs (such as patients with dementia or depression). Antipsychotic drugs with
      strong 5-HT2 antagonism seem to be more frequently associated with hypothermia.
      These cases demonstrate the clinical relevance of hypothermia as an adverse
      reaction to antipsychotic treatment and the importance of careful monitoring of
      body temperature.

PMID- 21956610
TI  - Bilaterality in papillary thyroid carcinoma: does it influence prognosis?

PMID- 21956609
TI  - CD6 attenuates early and late signaling events, setting thresholds for T-cell
      activation.
AB  - The T lineage glycoprotein CD6 is generally considered to be a costimulator of T
      cell activation. Here, we demonstrate that CD6 significantly reduces early and
      late T-cell responses upon superantigen stimulation or TCR triggering by Abs.
      Measuring calcium mobilization in single cells responding to superantigen, we
      found that human T cells expressing rat CD6 react significantly less well
      compared with T cells not expressing the exogenous receptor. When the cytoplasmic
      domain of rat CD6 was removed, calcium responses were recovered, indicating that
      the inhibitory properties of CD6 are attributable to its cytoplasmic domain.
      Calcium responses, and also late indicators of T-cell activation such as IL-2
      release, were also diminished in TCR-activated Jurkat cells expressing human CD6,
      compared with CD6-deficient cells or cells expressing a cytoplasmic deletion
      mutant of human CD6. Similarly, calcium signals triggered by anti-CD3 were
      enhanced in human T lymphocytes following morpholino-mediated suppression of CD6
      expression. Finally, the proliferation of T lymphocytes was increased when the
      CD6-CD166 interaction was blocked with anti-CD166 Abs, but inhibited when anti
      CD6 Abs were used. Our data suggest that CD6 is a signaling attenuator whose
      expression alone, i.e. in the absence of ligand engagement, is sufficient to
      restrain signaling in T cells.

PMID- 21956611
TI  - Brain processes in discounting: consequences of adolescent methylphenidate
      exposure.
AB  - Traits of inattention, impulsivity, and motor hyperactivity characterize children
      diagnosed with attention-deficit/hyperactivity disorder (ADHD), whose inhibitory
      control is reduced. In animal models, crucial developmental phases or
      experimental transgenic conditions account for peculiarities, such as sensation
      seeking and risk-taking behaviors, and reproduce the beneficial effects of
      psychostimulants. An "impulsive" behavioral profile appears to emerge more
      extremely in rats when forebrain dopamine (DA) systems undergo remodeling, as in
      adolescence, or with experimental manipulation tapping onto the dopamine
      transporter (DAT). Ritalin((r)) (methylphenidate, MPH), a DAT-blocking drug, is
      prescribed for ADHD therapy but is also widely abused by human adolescents.
      Administration of MPH during rats' adolescence causes a long-term modulation of
      their self-control, in terms of reduced intolerance to delay and diminished
      proneness for risk when reward is uncertain. Exactly the opposite profile emerges
      when exogenous alteration of DAT levels is achieved via lentiviral transfection.
      Both adolescent MPH exposure and DAT-targeting transfection lead to enduring
      hyperfunction of dorsal striatum and hypofunction of ventral striatum. Together
      with upregulation of prefronto-cortical phospho-creatine, striatal upregulation
      of selected genes (like serotonin 7 receptor gene) suggests that enhanced
      inhibitory control is generated by adolescent MPH exposure. Operant tasks, which
      assess the balance between motivational drives and inhibitory self-control, are
      thus useful for investigating reward-discounting processes and their modulation
      by DAT-targeting tools. In summary, due to the complexity of human studies,
      preclinical investigations of rodent models are necessary to understand better
      both the neurobiology of ADHD-like symptoms' etiology and the long-term
      therapeutic safety of adolescent MPH exposure.

PMID- 21956612
TI  - Face processing in attention deficit/hyperactivity disorder.
AB  - ADHD is one of the most common and impairing psychiatric conditions affecting
      children today. Thus far, much of the phenomenological and neurobiological
      research has emphasized the core symptoms of inattention, hyperactivity, and
      impulsivity which are thought to be mediated by frontostriatal alterations.
      However, increasing evidence suggests that ADHD involves emotional problems in
      addition to cognitive impairments. Here, we review the neurobiology of face
      processing and suggest that face-processing alterations offer a window into the
      emotional dysfunction often accompanying ADHD.

PMID- 21956613
TI  - The four causes of ADHD: a framework.
AB  - In addition to the symptoms singled out by the diagnostic criteria for Attention
      Deficit Hyperactivity Disorder (ADHD), a comprehensive definition should inform
      us of the events that trigger ADHD in both its acute and chronic manifestations;
      the neurobiology that underlies it; and the evolutionary forces that have kept it
      in the germ line of our species. These factors are organized in terms of
      Aristotle's four kinds of "causes," or explanations: formal, efficient, material,
      and final. This framework systematizes the nosology, biology, psychology, and
      evolutionary pressures that cause ADHD.

PMID- 21956614
TI  - SVEEVA descriptor application to peptide QSAR.
AB  - A new descriptor, SVEEVA (principal component scores vector of electronic
      eigenvalue descriptors), was derived from principal component analysis (PCA) of a
      matrix of 220 electronic eigenvalue descriptors of coded amino acids. SVEEVA
      scales were then applied in three panels of peptide quantitative structure
      activity relationship (QSAR) that were modeled by partial least squares
      regression (PLS). The obtained models with the correlation coefficient (R2(cum),
      cross-validation correlation coefficient (Q2(LOO) were 0.894 and 0.839 for 58
      angiotensin-converting enzyme inhibitors, 0.995 and 0.949 for 12 antimicrobial
      polypeptides, and 0.995 and 0.976 for 20 thromboplastin inhibitors. Satisfactory
      results showed that information related to biological activity can be
      systemically expressed by SVEEVA scales, which may be a useful structural
      expression methodology for study on peptide QSAR.

PMID- 21956617
TI  - Commercial factors override science in combination addiction drug trial.

PMID- 21956615
TI  - Liddle syndrome in a Serbian family and literature review of underlying
      mutations.
AB  - Severe and reproducible low-renin hypertension responsive to salt restriction and
      amiloride-thiazide therapy in a 13-year-old otherwise asymptomatic boy suggested
      Liddle syndrome. This assumption was strengthened by a positive family history of
      hypertension poorly responsive to conventional treatment or sudden deaths under
      40 years of age in four generations. DNA analysis of the beta and gamma subunits
      of the epithelial sodium channel revealed a heterozygous mutation c.C1852T
      (p.Pro618Ser) in the SCNN1B gene in the patient and in both his hypertensive
      mother and uncle. A PubMed search revealed 21 different disease-causing mutations
      reported to date, all but two clustering in the cytoplasmic C-terminal regions of
      either beta (16 mutations) or gamma (5) subunit, leading to a three- to eightfold
      increase in the amiloride-sensitive sodium current. Inter- and intrafamilial
      variability in both hypertension and hypokalemia were disclosed, which may not be
      obligatory among the subjects carrying a Liddle mutation. CONCLUSION: Liddle
      syndrome should be considered as a cause of hypertension in children or
      adolescents particularly with suppressed renin activity. Early diagnosis and
      appropriately tailored treatment avoid complications of long-term unrecognized or
      inappropriately managed hypertension.

PMID- 21956618
TI  - A common 5'-UTR variant in MATE2-K is associated with poor response to metformin.
AB  - Multidrug and toxin extrusion 2 (MATE2-K (SLC47A2)), a polyspecific organic
      cation exporter, facilitates the renal elimination of the antidiabetes drug
      metformin. In this study, we characterized genetic variants of MATE2-K,
      determined their association with metformin response, and elucidated their impact
      by means of a comparative protein structure model. Four nonsynonymous variants
      and four variants in the MATE2-K basal promoter region were identified from
      ethnically diverse populations. Two nonsynonymous variants-c.485C>T and c.1177G>A
      were shown to be associated with significantly lower metformin uptake and
      reduction in protein expression levels. MATE2-K basal promoter haplotypes
      containing the most common variant, g.-130G>A (>26% allele frequency), were
      associated with a significant increase in luciferase activities and reduced
      binding to the transcriptional repressor myeloid zinc finger 1 (MZF-1). Patients
      with diabetes who were homozygous for g.-130A had a significantly poorer response
      to metformin treatment, assessed as relative change in glycated hemoglobin
      (HbA1c) (-0.027 (-0.076, 0.033)), as compared with carriers of the reference
      allele, g.-130G (-0.15 (-0.17, -0.13)) (P=0.002). Our study showed that MATE2-K
      plays a role in the antidiabetes response to metformin.

PMID- 21956620
TI  - Assessment of the electronic properties of P ligands stemming from secondary
      phosphine oxides.
AB  - We report the study of the net donating ability of monodentate and bidentate P
      ligands stemming from secondary phosphine oxides (SPOs). We experimentally
      measured and/or calculated the frequencies of CO stretching modes of various
      metal carbonyl complexes. The inferred electronic properties of the ligands span
      an unprecedented range, going from pi-accepting phosphite-like compounds, to
      extremely electron-donating ligands outclassing N-heterocyclic carbenes.

PMID- 21956619
TI  - FITC labeled silica nanoparticles as efficient cell tags: uptake and
      photostability study in endothelial cells.
AB  - The use of fluorescent nanomaterials has gained great importance in the field of
      medical imaging. Many traditional imaging technologies have been reported
      utilizing dyes in the past. These methods face drawbacks due to non-specific
      accumulation and photobleaching of dyes. We studied the uptake and
      internalization of two different sized (30 nm and 100 nm) FITC labeled silica
      nanoparticles in Human umbilical vein endothelial cell line. These nanomaterials
      show high biocompatability and are highly photostable inside live cells for
      increased period of time in comparison to the dye alone. To our knowledge, we
      report for the first time the use of 30 nm fluorescent silica nanoparticles as
      efficient endothelial tags along with the well studied 100 nm particles. We also
      have emphasized the good photostability of these materials in live cells.

PMID- 21956621
TI  - Preventive youth health care in 11 European countries: an exploratory analysis.
AB  - OBJECTIVE: To systematically identify similarities and differences in the way
      preventive youth health care (YHC) is organized in 11 European countries. METHOD:
      Questionnaire survey to EUSUHM (European Union for School and University Health
      and Medicine) representatives. RESULTS: The greatest similarities were found in
      the age range of the YHC target group and the separation of curative and
      preventive services. Croatia, Germany and Switzerland show the greatest
      differences when compared to other European countries, for example, in the access
      to medical records, YHC professional input and the number of examinations,
      immunizations and screenings. In eight countries YHC is financed by national
      insurances or taxation. In Germany, FYR Macedonia, the Netherlands, Russia and
      Switzerland, different forms of financing exist in parallel. CONCLUSION: The
      results should be interpreted as a preliminary step in mapping organizational
      features of YHC in Europe.

PMID- 21956622
TI  - Multifunctional response of anatase nanostructures based on 25 nm mesocrystal
      like porous assemblies.

PMID- 21956623
TI  - Treatment of tics in patients with Tourette syndrome: recommendations according
      to the European Society for the Study of Tourette Syndrome.

PMID- 21956624
TI  - Benchmark results for empirical post-GGA functionals: difficult exchange problems
      and independent tests.
AB  - Many of the most promising new density functionals have improved the treatment of
      non-local exchange effects with the help of semi-empirical information and more
      sophisticated recipes for combining Hartree-Fock and local exchange
      approximations. In order to quantify recent advancements and identify directions
      for improvement, we have examined a broad spectrum of test problems. We evaluate
      the performance of several new hybrid density functionals (omegaB97, omegaB97X,
      omegaB97X-D, LRC-omegaPBEh, M06, M06-2X, and M06-HF) on a variety of chemical
      problems, some sensitive to the treatment of exact exchange (which we have hoped
      to systematically improve) and some which require a balanced treatment of
      correlation. Since all of the functionals under consideration are parameterized
      with ground-state thermochemical data, the benchmark aims to determine the
      applicability of the new density functionals to cases that have not been
      considered in the optimization of the semi-empirical parameters. The first class
      of benchmarks includes the excitation energies of 21 molecules (83 states)
      primarily from a recent benchmark conducted by Tozer and co-workers, with some
      additional references from data made available from the groups of Thiel and
      Truhlar. We briefly examine the conformational preferences of a small peptide and
      complete our study with two recently published sets of data that have shown
      large, systematic errors in simple alkane thermochemistry. While our results
      indicate that the more general hybrids currently under development perform well
      for problems outside of their parameterization and improve over the standard
      hybrid density functionals in an essentially systematic way, there is still a
      significant self-interaction error in the more difficult cases. Functionals based
      on a range-separation of exchange and functionals depending on the kinetic-energy
      density both perform comparably, and there is evidence for complementary
      strengths.

PMID- 21956625
TI  - Acne scars in ethnic skin treated with both non-ablative fractional 1,550 nm and
      ablative fractional CO2 lasers: comparative retrospective analysis with
      recommended guidelines.
AB  - BACKGROUND: Fractional technology has changed the dermatologists view in how to
      treat acne scars in ethnic skin as a result of its favorable safety profile.
      OBJECTIVES: To evaluate the safety and efficacy of non-ablative fractional (NAF)
      1,550 nm and ablative fractional (AF) CO(2) Lasers in the treatment of acne scars
      in ethnic skin. METHODOLOGY: In this retrospective analysis patients with acne
      scars who were treated with NAF 1,550 nm or AF CO(2) lasers from January 2008
      until July 2009 were included. Evaluation was made through comparing pre- and
      post-photographs and physician global assessment. Patients' satisfaction rate was
      also recorded. Assessment of improvement was based on a quartile grading scale.
      Bleaching creams and oral antibiotics were routinely given after each session.
      Adverse effects were recorded. Follow up visits were scheduled at weeks 1 and 4
      of each session and 12 weeks post-last session. RESULTS: A total of 82 patients
      were recruited in the study. Forty-five patients treated with NAF 1,550 nm laser
      and 37 patients with AF CO(2) laser. Skin phototype was mainly type IV (III-V).
      An overall patient satisfaction was 71% for NAF 1,550 nm laser group and 65% for
      AF CO(2) laser group. Thirty-five percent and 37% of patients attained more than
      50% improvement with NAF 1,550 nm and AF CO(2) lasers, respectively. Patients
      treated with NAF 1,550 nm laser had less down time. Transient post-inflammatory
      hyperpigmentation (PIH) was noted in 17% of patients treated with NAF 1,550 nm
      laser compared to 14% with AF CO(2) . CONCLUSION: Both NAF 1,550 nm and AF CO(2)
      lasers are effective in treating acne scars in ethnic skin with good patient
      satisfaction rate and high safety profile. PIH decreased with routine use of
      prophylactic bleaching creams. Fractional laser resurfacing open a wide horizon
      for treating acne scars in ethnic skin.

PMID- 21956626
TI  - When not to treat cutaneous vascular lesions with the pulsed dye laser.
AB  - The availability of effective laser treatment for cutaneous vascular lesions has
      risen dramatically in recent years. At the same time, there has been a
      proliferation of laser providers with varying amounts of training-both medical
      and nonmedical. We report a series of four cases where patients presented for
      cosmetic evaluation of vascular lesions and were discovered to have more
      significant pathologic disease. In presenting these cases, we hope to illuminate
      a basic differential diagnosis that exists for cutaneous vascular lesions and
      remind healthcare providers that not all "cosmetic" concerns are benign in
      origin. There is a differential diagnosis that exists for cutaneous vascular
      lesions that is worth reviewing, and it should be considered in all patients
      presenting for laser treatment.

PMID- 21956627
TI  - Interstitial laser photocoagulation for benign thyroid nodules: time to treat
      large nodules.
AB  - BACKGROUND AND OBJECTIVE: Interstitial laser photocoagulation (ILP) is a new
      therapeutic option for the ablation of non-functioning and hyper-functioning
      benign thyroid nodules. Amelioration of the ablation procedure currently allows
      treating large nodules. Aim of this study was to evaluate the therapeutic
      efficacy of ILP, performed according to a modified protocol of ablation, in
      patients with large functioning and non-functioning thyroid nodules and to
      identify the best parameters for predicting successful outcome in hyperthyroid
      patients. MATERIALS AND METHODS: Fifty-one patients with non-functioning thyroid
      nodules (group 1) and 26 patients with hyperfunctioning thyroid nodules (group 2)
      were enrolled. All patients had a nodular volume >=40 ml. Patients were addressed
      to 1-3 cycles of ILP. A cycle consisted of three ILP sessions, each lasting 5-10
      minutes repeated at an interval of 1 month. After each cycle of ILP patients
      underwent thyroid evaluation. RESULTS: A nodule volume reduction, expressed as
      percentage of the basal volume, significantly occurred in both groups (F = 190.4;
      P < 0.0001 for group 1 and F = 100.2; P < 0.0001 for group 2). Receiver-operator
      characteristic (ROC) curves were constructed for: (i) percentage of volume
      reduction; (ii) difference in nodule volume; (iii) total amount of energy
      delivered expressed in Joule. ROC curves identified the percentage of volume
      reduction as the best parameter predicting a normalized serum TSH (area under the
      curve 0.962; P < 0.0001). Intraoperative complications consisted in: (i) mild
      pain occurring in five (6.5%) patients, (ii) vasovagal reaction in two (2.6%)
      patients, (iii) fever within 24 hours from ILP in five (6.5%) patients. No major
      complications including persistent pain, laringeal nerve dysfunction,
      hypoparathyroidism, pseudocystic transformation, and/or neck fascitis were
      observed. CONCLUSIONS: ILP represents a valid alternative to surgery also for
      large benign thyroid nodules, both in terms of nodule size reduction and cure of
      hyperthyroidism (87% of cured patients after the last ILP cycle). ILP should not
      be limited to patients refusing or being ineligible for surgery and/or
      radioiodine.

PMID- 21956628
TI  - Enhanced uptake and photoactivation of topical methyl aminolevulinate after
      fractional CO2 laser pretreatment.
AB  - BACKGROUND AND OBJECTIVES: Photodynamic therapy (PDT) of thick skin lesions is
      limited by topical drug uptake. Ablative fractional resurfacing (AFR) creates
      vertical channels that may facilitate topical PDT drug penetration and improve
      PDT-response in deep skin layers. The purpose of this study was to evaluate
      whether pre-treating the skin with AFR before topically applied methyl
      aminolevulinate (MAL) could enable a deep PDT-response. MATERIALS AND METHODS:
      Yorkshire swine were treated under general anesthesia with a fractional CO(2)
      laser using stacked single pulses of 3 milliseconds, 91.6 mJ per pulse and
      subsequent topical MAL application for 3 hours (Metvix(r)). Red light (LED
      arrays) was then delivered at fluences of 37 and 200 J/cm(2). Fluorescent
      photography and microscopy was used to quantify MAL-induced porphyrin
      distribution and PDT-induced photobleaching at the skin surface and five specific
      depths down to 1,800 um. RESULTS: Laser-ablated channels were approximately 1,850
      um deep, which significantly increased topical MAL-induced porphyrin fluorescence
      (hair follicles, dermis, P < 0.0001) and PDT response, both superficially and
      deep, versus topical MAL application alone. The fraction of porphyrin
      fluorescence lost by photobleaching was slightly less after 37 J/cm(2) than after
      200 J/cm(2) (overall median values 67-90%; 37 vs. 200 J/cm(2), P > 0.05 for all
      but one comparison). Photobleaching was steady throughout skin layers and did not
      vary significantly with skin depth at either LED fluence (P > 0.05). CONCLUSIONS:
      AFR greatly facilitates topical MAL-induced porphyrins and the fraction of
      photobleached porphyrins is similar for superficial and deep skin. These
      observations are consistent with AFR-enhanced uptake of MAL, increased porphyrin
      synthesis, and photodynamic activation of deep porphyrins even at the lower
      fluence of 37 J/cm(2), widely used in clinical practice. AFR appears to be a
      clinically practical means for improving PDT deep into the skin. Clinical studies
      are suggested to evaluate selectivity in targeting dysplastic cell types.

PMID- 21956629
TI  - Mechanical tissue optical clearing technique increases imaging resolution and
      contrast through ex vivo porcine skin.
AB  - BACKGROUND AND OBJECTIVES: Mechanical tissue optical clearing permits light
      delivery deeper into turbid tissue, which may improve current optical diagnostics
      and laser-based therapeutic techniques. We investigated the effects of localized
      compression on brightfield imaging through ex vivo porcine skin by evaluating
      resolution and contrast of a target positioned beneath native, mechanically
      compressed, or chemically cleared specimens. We also evaluated the effects of
      indentation on dynamic tissue thickness and light transmission. STUDY
      DESIGN/METHODS: A 5 mm diameter, hemispherically tipped, manual load transducer
      was used to compress specimens using 2-44 N for 60 seconds. Chemically cleared
      specimens were immersed for 1 hour in glycerol or dimethyl sulfoxide. A USAF 1951
      resolution target was positioned beneath specimens and imaged using brightfield
      microscopy. Resolution and contrast of target features were analyzed. In separate
      experiments, a mechanical test instrument was used to compress and hold specimens
      at a final thickness while measuring applied load and light transmission.
      RESULTS: Image intensity profiles showed that while uncompressed skin did not
      allow resolution of any target, localized compression allowed maximum resolution
      up to a line width of 173 +/- 21 um. Mechanical clearing achieved up to four
      times higher maximum resolution and 2-3 times higher contrast sensitivity than
      chemical immersion. Resolving capability was highly correlated with compressive
      tissue strain. Light transmission increased during tissue compression, but also
      increased while holding final thickness constant. CONCLUSION: Localized
      compression is an effective technique for increasing resolution and contrast of
      target features through tissue and may improve light-based diagnostics. Thickness
      reduction and other mechanisms appear to contribute to this effect.

PMID- 21956630
TI  - Rapid and selective removal of composite from tooth surfaces with a 9.3 um CO2
      laser using spectral feedback.
AB  - OBJECTIVE: Dental composite restorative materials are color matched to the tooth
      and are difficult to remove by mechanical means without excessive removal or
      damage to peripheral enamel and dentin. Lasers are ideally suited for selective
      ablation to minimize healthy tissue loss when replacing existing restorations,
      sealants, or removing composite adhesives such as residual composite left after
      debonding orthodontic brackets. METHODS: In this study, a carbon dioxide laser
      operating at 9.3-um with a pulse duration of 10-20-microsecond and a pulse
      repetition rate of ~200 Hz was integrated with a galvanometer based scanner and
      used to selectively remove composite from tooth surfaces. Spectra of the plume
      emission were acquired after each laser pulse and used to differentiate between
      the ablation of dental enamel or composite. Microthermocouples were used to
      monitor the temperature rise in the pulp chamber during composite removal. The
      composite was placed on tooth buccal and occlusal surfaces and the carbon dioxide
      laser beam was scanned across the surface to selectively remove the composite
      without excessive damage to the underlying sound enamel. The residual composite
      and the damage to the underlying enamel was evaluated using optical microscopy.
      RESULTS: The laser was able to rapidly remove composite from tooth buccal and
      occlusal surfaces with minimal damage to the underlying sound enamel and without
      excessive heat accumulation in the tooth. CONCLUSION: This study demonstrated
      that composite can be selectively removed from tooth surfaces at clinically
      relevant rates using a CO(2) laser operating at 9.3-um with high pulse repetition
      rates with minimal heat deposition and damage to the underlying enamel.

PMID- 21956631
TI  - Assessment of pulpal vitality using laser speckle imaging.
AB  - BACKGROUND AND OBJECTIVE: The pulpal chamber of each tooth contains the
      vasculature necessary to maintain a viable tooth. A critical need exists to
      develop an objective, repeatable method to assess pulpal viability. We
      hypothesized that the existence of blood perfusion within the pulp can be
      determined with analysis of laser speckle imaging (LSI) patterns generated by
      transillumination of the tooth. STUDY DESIGN/MATERIALS AND METHODS: We used nine
      extracted human cuspids and incisors. A Tygon tube was inserted into a channel
      created within each tooth and Intralipid pumped through the tube in a controlled
      manner with a syringe infusion pump. We evaluated the feasibility of LSI for flow
      assessment using both transillumination and epiillumination imaging
      configurations. With the transillumination geometry, we also assessed the effect
      of the angle of incidence of the probe laser light on the speckle flow index
      (SFI) values extracted from the collected speckle images. RESULTS:
      Transillumination LSI, and not epiillumination LSI, enables differentiation
      between the absence and presence of perfusion in an in vitro tooth model. SFI
      values are insensitive to the relative angle of incidence of the laser light,
      over a wide range of angles. CONCLUSIONS: Our preliminary in vitro data suggest
      that transillumination LSI is a promising method to identify the presence of
      blood flow in the pulpal chamber. Future in vivo evaluation is warranted.

PMID- 21956632
TI  - High-frequency ultrasound imaging of noninvasive laser coagulation of the canine
      vas deferens.
AB  - BACKGROUND AND OBJECTIVES: A noninvasive approach to vasectomy may eliminate male
      fear of complications related to surgery (e.g., hematoma, infection, acute and
      chronic pain, sterilization failure) and increase its acceptance. Noninvasive
      laser thermal occlusion of the canine vas deferens has recently been reported. In
      this study, high-frequency ultrasound is used to confirm successful laser thermal
      coagulation and scarring of the vas in a short-term canine model. MATERIALS AND
      METHODS: Bilateral noninvasive laser coagulation of the vas was performed in a
      total of nine dogs using a laser wavelength of 1,075 nm, incident power of 9.0 W,
      pulse duration of 500 milliseconds, pulse rate of 0.5 Hz, and 3-mm-diameter spot.
      Cryogen spray was used to cool the scrotal skin surface and prevent burns during
      the procedure. A clinical ultrasound system with a 13.2-MHz high-frequency
      transducer was used to image the vas before and after the procedure. Burst
      pressure measurements were performed on excised vas to confirm thermal occlusion.
      RESULTS: Day 0 and 28 burst pressures averaged 291 +/- 31 mmHg and 297 +/- 26
      mmHg, respectively, significantly greater than ejaculation pressures of 136 +/-
      29 mmHg. Ultrasound showed a hyperechoic vas segment after thermal coagulation
      (Day 0) and scarring (Day 28). Doppler ultrasound showed normal blood flow
      through the testicular artery, indicating no collateral thermal damage to
      proximal structures. CONCLUSIONS: High-frequency ultrasound may be used as a
      noninvasive diagnostic tool to assist in determining successful short-term laser
      thermal coagulation and scarring of the vas.

PMID- 21956633
TI  - Laser photobiostimulation of wound healing: reciprocity of irradiance and
      exposure time on energy density for splinted wounds in diabetic mice.
AB  - BACKGROUND AND OBJECTIVES: We have used a 660 nm laser diode in genetic diabetic
      mice to stimulate the healing of wounds covered with a Tegaderm HP dressing that
      causes a retardation of contraction (splinted wounds). The influence of
      irradiance (power density) on wound healing has been examined with the same
      energy dose delivered to the wounds. This energy dose caused maximal stimulation
      of healing in a previous study. MATERIALS AND METHODS: A circular excisional
      wound was made on the left flank of diabetic mice using a 5-mm skin punch, and
      covered with a Tegaderm HP dressing. Four different treatments were tested:
      Treatment 1, not irradiated (control); treatment 2, 100 mW, 20 seconds; treatment
      3, 50 mW, 40 seconds; treatment 4, 25 mW, 80 seconds. Treatments were given daily
      for 7 days. The irradiances for treatments 2, 3, and 4 were estimated to be 233
      313, 116-156, and 58-78 mW/cm(2), respectively. In total, 53 mice were used.
      Wounds were harvested on day 14 and healing assessed from hematoxylin-eosin
      stained sections examined by light microscopy. RESULTS: The wounds were splinted
      in 42 of the mice, and splinting caused a retardation of healing. The findings
      showed that wound healing was stimulated to a similar extent by treatments 2, 3,
      and 4 and occurred mainly by reepithelization and granulation tissue formation.
      The laser parameters used represent an energy dose of 2.0 J per irradiation and,
      for an estimated area of irradiation of 32-43 mm(2), corresponds to an energy
      density of 4.7-6.3 J/cm(2). CONCLUSION: Irradiation 660 nm with irradiances
      estimated to be 233-313, 116-156, and 58-78 mW/cm(2) and an estimated energy
      density of 4.7-6.3 J/cm(2) each day for 7 days stimulated healing to a similar
      extent in splinted wounds of diabetic mice.

PMID- 21956634
TI  - Dose response effects of 810 nm laser light on mouse primary cortical neurons.
AB  - BACKGROUND AND OBJECTIVES: In the past four decades numerous studies have
      reported the efficacy of low level light (laser) therapy (LLLT) as a treatment
      for diverse diseases and injuries. Recent studies have shown that LLLT can
      biomodulate processes in the central nervous system and has been extensively
      studied as a stroke treatment. However there is still a lack of knowledge on the
      effects of LLLT at the cellular level in neurons. The present study aimed to
      study the effect of 810 nm laser on several cellular processes in primary
      cortical neurons cultured from embryonic mouse brains. STUDY DESIGN/MATERIALS AND
      METHODS: Neurons were irradiated with fluences of 0.03, 0.3, 3, 10, or 30 J/cm(2)
      of 810-nm laser delivered over varying times at 25 mW/cm(2) and intracellular
      levels of reactive oxygen species (ROS), nitric oxide and calcium were measured
      using fluorescent probes within 5 minutes of the end of irradiation. The changes
      in mitochondrial function in response to light were studied in terms of adenosine
      triphosphate (ATP) and mitochondrial membrane potential (MMP). RESULTS: Light
      induced a significant increase in calcium, ATP and MMP at lower fluences and a
      decrease at higher fluences. ROS was significantly induced at low fluences,
      followed by a decrease and a second larger increase at 30 J/cm(2). Nitric oxide
      levels showed a similar pattern of a double peak but values were less significant
      compared to ROS. CONCLUSIONS: The results suggest that LLLT at lower fluences is
      capable of inducing mediators of cell signaling processes which in turn may be
      responsible for the beneficial stimulatory effects of the low level laser. At
      higher fluences beneficial mediators are reduced and high levels of Janus-type
      mediators such as ROS and NO (beneficial at low concentrations and harmful at
      high concentrations) may be responsible for the damaging effects of high-fluence
      light and the overall biphasic dose response.

PMID- 21956636
TI  - Athrombogenic coating of long-term venous catheter for cancer patients: a
      prospective, randomised, double-blind trial.
AB  - Cancer patients with long-term venous catheter are at risk for thromboembolic
      complications at the catheter tip and in the adjacent venous vessels. We assessed
      whether local thrombogenicity could be prevented with an experimental coated
      (with athrombogenic layer) catheter device (CD) compared to an uncoated CD.
      Patients requiring a long-term venous catheter were randomly allocated to receive
      either a standard uncoated or experimental coated (with athrombogenic
      Camouflage(r) layer) CD. The athrombogenic layer creates a barrier against non
      specific adsorption of plasma proteins. The primary endpoint was urokinase
      injection in cases of an unsuccessful blood aspiration from the CD. Secondary
      endpoints included early (haematoma, pneumothorax) and late (venous thrombosis,
      infection) catheter-associated complications and catheter defects. One hundred
      and seventy-nine patients were randomly assigned to a CD (experimental n =
      89/standard n = 90). One hundred and ten (62%) patients with a total of 1,286
      catheter taps were analysed for the primary endpoint. Necessity for urokinase
      injection was 8/680 (1.2% experimental) vs. 33/606 (5.4% standard) per catheter
      tap and 4/55 (7.3% experimental) vs. 18/55 (32.7% standard) per patient. A
      repeated measures logistic regression to assess the effect of coating yielded an
      odds ratio of 3.5 (95% confidence interval, 1.2-10.4; p = 0.03) for the primary
      endpoint. All patients allocated per protocol were analysed for the secondary
      endpoints. Nine (5.4%) local thrombotic complications, seven (4.1%) catheter
      infections, and no catheter defect were observed. Athrombogenic coating of CD in
      cancer patients resulted in a significant reduced necessity for urokinase
      injections and subsequently less inconvenience for patients and fewer costly
      interventions.

PMID- 21956638
TI  - Accumulating microparticles and direct-writing micropatterns using a continuous
      wave laser-induced vapor bubble.
AB  - Through the enhanced photothermal effect, which was achieved using a silver film,
      a low power weakly focused continuous-wave laser (532 nm) was applied to create a
      vapor bubble. A convective flow was formed around the bubble. Microparticles
      dispersed in water were carried by the convective flow to the vapor bubble and
      accumulated on the silver film. By moving the laser spot, we easily manipulated
      the location of the bubble, allowing us to direct-write micropatterns on the
      silver film with accumulated particles. The reported simple controllable
      accumulation method can be applied to bimolecular detection, medical diagnosis,
      and other related biochip techniques.

PMID- 21956637
TI  - Osteoblast extracellular Ca2+ -sensing receptor regulates bone development,
      mineralization, and turnover.
AB  - The extracellular Ca(2+) -sensing receptor (CaR), a G protein-coupled receptor
      responsible for maintenance of calcium homeostasis, is implicated in regulation
      of skeletal metabolism. To discern the role of the osteoblast CaR in regulation
      of bone development and remodeling, we generated mice in which the CaR is excised
      in a broad population of osteoblasts expressing the 3.6-kb a(1) (I) collagen
      promoter. Conditional knockouts had abnormal skeletal histology at birth and
      developed progressively reduced mineralization secondary to retarded osteoblast
      differentiation, evident by significantly reduced numbers of osteoblasts and
      decreased expression of collagen I, osteocalcin, and sclerostin mRNAs. Elevated
      expression of ankylosis protein, ectonucleotide pyrophosphatase/phosphodiesterase
      1, and osteopontin mRNAs in the conditional knockout indicate altered regulation
      of genes important in mineralization. Knockout of the osteoblast CaR also
      resulted in increased expression of the receptor activator of NF-kappaB ligand
      (RANKL), the major stimulator of osteoclast differentiation and function,
      consistent with elevated osteoclast numbers in vivo. Osteoblasts from the
      conditional knockouts exhibited delayed differentiation, reduced mineralizing
      capacity, altered expression of regulators of mineralization, and increased
      ability to promote osteoclastogenesis in coculture experiments. We conclude that
      CaR signaling in a broad population of osteoblasts is essential for bone
      development and remodeling and plays an important role in the regulation of
      differentiation and expression of regulators of bone resorption and
      mineralization.

PMID- 21956639
TI  - Cytokines and organ failure in acute pancreatitis: inflammatory response in acute
      pancreatitis.
AB  - OBJECTIVES: We aimed at synchronously examining the early time course of 4
      proinflammatory cytokines as predictive factors for development of organ failure
      in patients with acute pancreatitis (AP). METHODS: Interleukin (IL) 6, IL-8, IL
      18, and tumor necrosis factor alpha were measured on admission and at days 1, 2,
      and 14 in 60 patients admitted with first attack of AP. The prediction of single
      organ and multiorgan failure from the cytokine profiles was evaluated by receiver
      operating characteristic analyses. RESULTS: Interleukin 6 and IL-8 levels were
      significantly higher in patients who developed renal, respiratory, and
      circulatory failure, as was the case for patients with multiorgan failure.
      Interleukin 18 levels were significantly elevated in renal and respiratory
      failure only. Tumor necrosis factor alpha was significantly elevated in all types
      of organ failures, except for intestinal failure. CONCLUSIONS: Synchronous
      measurements of 4 cytokines demonstrated IL-6 and IL-8 to be predictive as early
      surrogate markers with regard to organ failures in AP. The fact that all of the
      cytokines were particularly elevated in patients with organ failures calls for
      evaluation of agents modifying the severe inflammatory response in patients with
      AP.

PMID- 21956640
TI  - Redefining transplant in acute leukemia.
AB  - OPINION STATEMENT: Assigning the correct treatment to those with acute leukemia
      is challenging and requires careful assessment of both the disease and the
      patient. Our ability to assign relapse risk to disease is evolving and
      incorporates cytogenetics, molecular lesions, and assessment of minimal residual
      disease after initial treatment. Allogeneic hematopoietic progenitor cell
      transplantation (alloHCPT) is one of the most efficacious treatments available to
      the physician. In adult acute lymphoblastic leukemia (ALL) despite the treatment
      risk, patients with a matched sibling who achieve CR should be referred for
      transplant. Prospective trials investigating the role of unrelated donors are in
      progress. There is little prospective evidence, but nonetheless encouraging data,
      to support referring older patients for alloHPCT using reduced intensity
      conditioning (RIC) regimens. In acute myeloid leukemia (AML), all high-risk
      patients and the majority of intermediate-risk patients with a matched sibling
      should be offered alloHPCT in CR1. In addition there is evidence that some
      patients previously assigned as good-risk would benefit from sibling transplant.
      Use of unrelated donors will expand the numbers eligible for transplant and
      should be considered when a matched-sibling is not available particularly in high
      risk patients. Similarly to ALL, the use of RIC is allowing transplantation to be
      offered to those deemed too old or unfit for myeloablative conditioning. The
      importance of enrolling patients into suitable prospective clinical trials cannot
      be overstated.

PMID- 21956641
TI  - Acute lymphoblastic leukemia of adulthood: progress or not?
AB  - OPINION STATEMENT: Much new information about ALL in adults has recently been
      learned from major clinical and laboratory studies. However, much of the recently
      reported improved management of this leukemia pertains only to younger patients.
      Elderly patients do not fair very well with modern therapy, including intensified
      treatment approaches. The question arises whether current treatment may be
      unnecessarily intensive, not only for elderly patients but for most patients.
      There are no prospective, randomized studies that clearly demonstrate that
      anthracyclines, cyclophosphamide or cytarabine are required for optimal results
      in this leukemia. Eliminating drugs of marginal value but with the potential for
      considerable toxicity may allow us to intensify treatment with drugs that are
      most effective at a cost of even less toxicity than usually expected.

PMID- 21956643
TI  - Ghrelin receptors are expressed by distal tubules of the mouse kidney.
AB  - Ghrelin, a peptide hormone from the stomach, has been recently discovered to
      reduce sodium excretion from the kidney. Although the effects on the kidney
      suggest actions in the distal nephron, the sites of expression of ghrelin
      receptors have not been localised. In the present work we have used a mouse that
      expresses green fluorescent protein under the control of the ghrelin receptor
      promoter to locate sites of receptor expression in the kidney. Receptor
      expression was confined to the straight parts of the distal tubules and the thin
      limbs of the loops of Henle. No expression was detected in other structures,
      including the glomeruli, proximal tubules and collecting ducts. Ghrelin receptors
      were not found in extra-renal or intra-renal arteries, despite observations that
      ghrelin is a vasodilator. The distribution revealed by in situ hybridisation
      histochemistry was the same as that revealed by the reporter. In conclusion,
      ghrelin receptors have a restricted distribution in the kidney. The location in
      the straight parts of the distal tubules accords with observations that ghrelin
      promotes sodium retention.

PMID- 21956644
TI  - Coping with HIV stigma: do proactive coping and spiritual peace buffer the effect
      of stigma on depression?
AB  - Although HIV stigma is a significant predictor of depression, little is known
      about which factors might most effectively buffer, or attenuate, this effect. We
      examined whether two coping-related factors-proactive coping and spiritual peace
      modified the effect of HIV stigma on likelihood of depression among a sample of
      465 people living with HIV/AIDS (PLWHA). In a cross-sectional analysis, we
      conducted hierarchical logistic regressions to examine the effect of HIV stigma,
      proactive coping, spiritual peace, and their interactions on likelihood of
      significant depressive symptoms. Spiritual peace moderated the effect of HIV
      stigma on depression at high-but not low-levels of HIV stigma. No such effect was
      observed for proactive coping. Findings suggest that spiritual peace may help
      counteract the negative effect of HIV stigma on depression. Intervention
      components that enhance spiritual peace, therefore, may potentially be effective
      strategies for helping PLWHA cope with HIV stigma.

PMID- 21956642
TI  - The interesting interplay between interneurons and adult hippocampal
      neurogenesis.
AB  - Adult neurogenesis is a unique form of plasticity found in the hippocampus, a
      brain region key to learning and memory formation. While many external stimuli
      are known to modulate the generation of new neurons in the hippocampus, little is
      known about the local circuitry mechanisms that regulate the process of adult
      neurogenesis. The neurogenic niche in the hippocampus is highly complex and
      consists of a heterogeneous population of cells including interneurons. Because
      interneurons are already highly integrated into the hippocampal circuitry, they
      are in a prime position to influence the proliferation, survival, and maturation
      of adult-generated cells in the dentate gyrus. Here, we review the current state
      of our understanding on the interplay between interneurons and adult hippocampal
      neurogenesis. We focus on activity- and signaling-dependent mechanisms, as well
      as research on human diseases that could provide better insight into how
      interneurons in general might add to our comprehension of the regulation and
      function of adult hippocampal neurogenesis.

PMID- 21956646
TI  - Palladium nanoparticles encapsulated in a metal-organic framework as efficient
      heterogeneous catalysts for direct C2 arylation of indoles.
AB  - Highly dispersed palladium nanoparticles (Pd NPs) encapsulated in the mesoporous
      cages of the metal-organic framework (MOF) MIL-101(Cr) have been prepared by
      using the wetness impregnation method. The Pd NPs were characterized by powder X
      ray diffraction (PXRD), N(2) adsorption, transmission electron microscopy,
      inductively coupled plasma atomic emission spectroscopy (ICP-AES), and X-ray
      photoelectron spectroscopy (XPS). The particles size ((2.6+/-0.5) nm) of the
      obtained Pd NPs was in good agreement with the cage diameters (2.9 and 3.4 nm) of
      the MOF. The resulting Pd/MIL-101(Cr) catalyst exhibited extremely high catalytic
      activities in the direct C2 arylation of substituted indoles by using only 0.1
      mol% of the Pd catalyst. Moreover, the catalyst is easily recoverable and can be
      reused several times without leaching into solution and loss of activity. The
      combination of the highly dispersible Pd NPs within the accessible mesoporous
      cages and the favorable adsorption of the aryl halides on MIL-101 are suspected
      to be the main reasons for the observed high activities of the Pd/MIL-101(Cr)
      catalyst in the direct C2 arylation of indoles.

PMID- 21956645
TI  - Synthesis and biological evaluation of 4alpha/4beta-imidazolyl podophyllotoxin
      analogues as antitumor agents.
AB  - A series of 4alpha/4beta-imidazolyl podophyllotoxin analogues have been designed
      and synthesized. All of the compounds were evaluated for their anticancer
      activity against a panel of three human cancer cell lines. Within the cell lines
      tested, some of the synthesized compounds showed promising anticancer activity.
      Compound 12, in particular, exhibited remarkable cytotoxicity, demonstrating
      effects against all tumor cell lines, including the K562/ADM cell line.

PMID- 21956647
TI  - Social and cultural factors associated with perinatal grief in Chhattisgarh,
      India.
AB  - Stillbirth is a globally significant public health problem with many medical
      causes. There are also indirect causal pathways including social and cultural
      factors which are particularly salient in India's traditional society. The
      purpose of this study was to explore women's perceptions of stillbirth and to
      determine how issues of gender and power, social support, coping efforts, and
      religious beliefs influence perinatal grief outcomes among poor women in rural
      Chhattisgarh, India. Structured interviews were done face-to-face in 21 randomly
      selected villages among women of reproductive age (N=355) who had experienced
      stillbirth (n=178) and compared to those who had not (n=177), in the Christian
      Hospital, Mungeli catchment area. Perinatal grief was significantly higher among
      women with a history of stillbirth. Greater perinatal grief was associated with
      lack of support, maternal agreement with social norms, and younger maternal age.
      These predictors must be understood in light of an additional finding-distorted
      sex ratios, which reflect gender discrimination in the context of Indian society.
      The findings of this study will allow the development of a culturally appropriate
      health education program which should be designed to increase social support and
      address social norms, thereby reducing psychological distress to prevent
      complicated perinatal grief. Perinatal grief is a significant social burden which
      impacts the health women.

PMID- 21956648
TI  - Profiles, perceptions and motivations of Community Health Workers of NGOs in a
      border city of US-Mexico.
AB  - To analyze the profile, perceptions and motivations of Community Health Workers
      (CHWs) from non-governmental organizations (NGOs) in the border city of US-Mexico
      and to describe the type of community interventions they perform. we surveyed 121
      CHWs from 9 NGOs participating in a monthly meeting between May and July of 2009.
      Each participating CHW answered a structured questionnaire. Furthermore, two
      focus groups were held, in which 10 and 8 CHWs participated, respectively.
      Qualitative and quantitative analyses were carried out on the data obtained. 70%
      of the CHWs had 9 years or less of formal education. With respect to community
      work, 61% volunteered between 1 and 5 h weekly; only 40% received some form of
      economic support. The most commonly reported activities were distribution of
      informational materials (59.5%) and promotion of health fairs (52.9%). Analysis
      of focus group discussions lead to the development of four conceptual categories:
      personal development, motivation, perception of their community participation and
      institutional relationship, some of the testimonies are "...just because the
      people do not respond does not mean we give up. No, we must work, persist,
      promote and raise awareness of the people...", "...when they compensate us, it is
      not really a payment. We are there because we get results, we do it happily... It
      is voluntary..." CHWs are an important human resource for communities.
      Institutions focusing on primary care should view these community players as
      social capital, which could improve the effectiveness of prevention strategies
      and achieve greater coverage of health services.

PMID- 21956649
TI  - Anodized aluminum oxide thin films for room-temperature-processed, flexible, low
      voltage organic non-volatile memory elements with excellent charge retention.

PMID- 21956650
TI  - Giant cell arteritis--a changing entity.
AB  - Giant cell arteritis (GCA) is the most common of the vasculitis syndromes and,
      being a disease of the elderly, its incidence is increasing with the general
      ageing of the population. GCA is most feared for its early complications, namely
      blindness and stroke, resulting from inflammation and subsequent occlusion of
      ocular and extra cranial arteries, respectively. More recently, however, GCA has
      been recognised to also affect limb arteries and the aorta with a high
      prevalence. These newly recognised features of GCA pose diagnostic, therapeutic
      and prognostic challenges to treating physicians. Here, recent developments in
      the field of GCA are summarised and discussed.

PMID- 21956651
TI  - [Perioperative anaphylaxis caused by rocuronium allergy in a child].
AB  - During the induction of anesthesia for strabismus correction, a six-year-old boy
      suffered anaphylaxis with hypotension. Midazolam, propofol, sufentanil,
      rocuronium, dexamethasone and ibuprofen had been administered. The boy's history
      failed to reveal any drug allergies. Intracutaneous testings with drugs used for
      anesthesia and other muscle relaxants verified a positive reaction to rocuronium
      as well as to cisatracurium, mivacurium, vecuronium and atracurium. There was no
      reaction to suxamethonium.

PMID- 21956652
TI  - TREM-2, triggering receptor expressed on myeloid cell-2, negatively regulates TLR
      responses in dendritic cells.
AB  - DCs play a key role in defense against infections and also in preventing
      inflammatory and autoimmune diseases. The response of DCs to pathogens is tightly
      regulated by many mechanisms to allow for appropriate, but not pathogenic,
      responses. We previously showed that DCs with deficiencies for two ITAM-bearing
      signaling adapters, DAP12 and FcRgamma, produce more inflammatory cytokines upon
      treatment with Toll-like receptor (TLR) agonists than WT DCs. Here, we
      investigated whether the TREM-2 receptor pairs with DAP12 to inhibit TLR
      responses in DCs. TREM-2-deficient BMDCs showed increased inflammatory cytokine
      and type I IFN production in response to TLR ligation. Additionally, TREM-2
      deficient BMDCs had increased TLR-induced maturation and were more efficient at
      inducing antigen-specific T-cell proliferation upon CpG DNA stimulation compared
      with WT BMDCs. Finally, we showed that a TREM-2 ligand is expressed on the
      surface of BMDCs, suggesting that the TREM-2 receptor transduces inhibitory
      signals due to recognition of an endogenous ligand.

PMID- 21956653
TI  - Dystonia in mitochondrial spinocerebellar ataxia and epilepsy syndrome associated
      with novel recessive POLG mutations.

PMID- 21956654
TI  - Circulating gammadelta T cells and the risk of acute-phase response after
      zoledronic acid administration.
AB  - The use of intravenous nitrogen-containing bisphosphonates (N-BPs) is associated
      with the appearance of an acute phase response (APR) in a proportion of the
      patients for reasons that are poorly understood. The APR was attributed to the
      indirect activation of gammadelta T cells with the release of interferon-gamma
      and tumor necrosis factor (TNF). Forty patients with postmenopausal or senile
      osteoporosis (age range = 53-91 years) never previously treated with intravenous
      (i.v.) bisphosphonate, received a single 5-mg zoledronic acid (ZOL) iv infusion
      over 15 minutes. White blood cells were counted and analyzed with an automated
      hematology analyzer (ADVIA 2120i Siemens, New York, USA) and by flow cytometer
      (BD FACSCanto, Becton Dickinson). The occurrence of APR was defined by the
      occurrence of fever (>37  degrees C) during the next 2 days. Forty-two percent of
      patients (17 of 40) receiving the infusion of ZOL experienced an APR. Compared
      with the others they were younger (69 +/- 7 years versus 74 +/- 8 years; p =
      0.06), and both the proportion and absolute number of gammadelta T cells were
      significant higher (p = 0.02 and p = 0.013, respectively). Nonsignificant
      differences were found between the two groups for white blood cells and for the
      other circulating lymphocyte subpopulations. Age was inversely correlated with
      circulating gammadelta T cells (p = 0.003) but the difference between the two
      groups in circulating gammadelta T cells persisted for age-adjusted values and
      vice versa. In conclusion, the results of this study indicate that the number of
      circulating gammadelta T cells, together with age, are important determinant of
      the occurrence of APR after intravenous infusion of ZOL and possibly of any other
      N-BPs.

PMID- 21956656
TI  - Identification of biomarkers for tuberculosis disease using a novel dual-color RT
      MLPA assay.
AB  - Owing to our lack of understanding of the factors that constitute protective
      immunity during natural infection with Mycobacterium tuberculosis (Mtb), there is
      an urgent need to identify host biomarkers that predict long-term outcome of
      infection in the absence of therapy. Moreover, the identification of host
      biomarkers that predict (in)adequate response to tuberculosis (TB) treatment
      would similarly be a major step forward. To identify/monitor multi-component host
      biomarker signatures at the transcriptomic level in large human cohort studies,
      we have developed and validated a dual-color reverse-transcriptase multiplex
      ligation-dependent probe amplification (dcRT-MLPA) method, permitting rapid and
      accurate expression profiling of as many as 60-80 transcripts in a single
      reaction. dcRT-MLPA is sensitive, highly reproducible, high-throughput, has an
      extensive dynamic range and is as quantitative as QPCR. We have used dcRT-MLPA to
      characterize the human immune response to Mtb in several cohort studies in two
      genetically and geographically diverse populations. A biomarker signature was
      identified that is strongly associated with active TB disease, and was profoundly
      distinct from that associated with treated TB disease, latent infection or
      uninfected controls, demonstrating the discriminating power of our biomarker
      signature. Identified biomarkers included apoptosis-related genes and T-cell/B
      cell markers, suggesting important contributions of adaptive immunity to TB
      pathogenesis.

PMID- 21956655
TI  - PSA regulates androgen receptor expression in prostate cancer cells.
AB  - BACKGROUND: Prostate-specific antigen (PSA) is a pivotal downstream target gene
      of the androgen receptor (AR), and a serum biomarker to monitor prostate cancer
      (PrCa) progression. It has been reported that PSA transactivates AR, but the
      mechanistic requirements of this response have not been investigated. METHODS: We
      studied the localization of PSA, AR, and Src in intracellular compartments of
      synthetic androgen (R1881)-stimulated LNCaP and C4-2B PrCa cells, using
      immunofluorescence and subcellular fractionation approaches. We also investigated
      the effect of downregulation of PSA on AR expression by immunoblotting and real
      time PCR using short hairpin RNA (shRNA) and small interfering RNA (siRNA). Src
      activity was analyzed by immunoblotting. RESULTS: R1881 stimulation induced
      nuclear localization of both PSA and AR in LNCaP and C4-2B PrCa cells as well as
      increased phosphorylation of Src. Stable shRNA or transient siRNA knockdown of
      PSA resulted in reduced AR protein levels as well as AR mRNA levels in C4-2B
      cells. Similar to C4-2B cells, ablation of AR levels upon silencing of PSA was
      also confirmed in VCaP cells, another androgen-independent cell line. Silencing
      of PSA did not cause significant changes in Src activation; besides, Src
      regulation by integrins did not appear to affect AR transcriptional activity.
      CONCLUSIONS: PSA localizes to nuclei of androgen-stimulated PrCa cells, and
      controls AR mRNA and protein levels. This regulatory loop is specific for PSA,
      does not involve known AR activators such as Src and AKT, and may contribute to
      AR signaling under conditions of increasing PSA levels in patients.

PMID- 21956657
TI  - Refinement of the genetics of the host response to Salmonella infection in
      MOLF/Ei: regulation of type 1 IFN and TRP3 pathways by Ity2.
AB  - Typhoid fever, which is caused by Salmonella typhi and paratyphi, is a severe
      systemic disease that remains a major public health issue in several areas of the
      world. We can model the human disease using mice infected with a related
      bacterium, Salmonella typhimurium. This model recapitulates several clinical
      aspects of the human disease and allows for the study of the host response to
      Salmonella typhimurium infection in vivo. Previous work in our laboratory has
      identified three Immunity to typhimurium loci (Ity, Ity2 and Ity3) in the wild
      derived MOLF/Ei mice, influencing survival after infection with Salmonella
      typhimurium. The MOLF/Ei alleles at Ity and Ity2 are protective, while the
      MOLF/Ei allele at Ity3 confers susceptibility. In this paper, we have generated a
      novel cross combination between the highly susceptible strain, MOLF/Ei, and the
      resistant strain, 129S6, to better define the genetic architecture of
      susceptibility to infection in MOLF/Ei. Using this cross, we have replicated the
      locus on chr 11 (Ity2) and identified a novel locus on chr 13 (Ity13). Using
      microarrays and transcriptional profiling, we examined the response of uninfected
      and infected Ity2 congenic mice. These analyses demonstrate a role for both type
      1-interferon (IFN) and TRP53 signaling in the pathogenesis of Salmonella
      infection.

PMID- 21956658
TI  - Mutualistic association of Paecilomyces formosus LHL10 offers thermotolerance to
      Cucumis sativus.
AB  - We investigated in this study the influence of an endophytic fungus, Paecilomyces
      formosus LHL10, on the thermotolerance of cucumber (Cucumis sativus) upon
      exposure to high (38 degrees C) and low (8 degrees C) temperature stresses. The
      results showed that endophyte-inoculated plants had significantly higher plant
      growth attributes under high-temperature stress. However, they were either low or
      insignificant in non-inoculated control and inoculated plants with 8 degrees C
      treatments. Lower stress-promulgated water deficit and cellular membrane damage
      were observed in endophyte-treated plants after 38 degrees C treatment than in
      control plants under 8 degrees C stress. Total polyphenol, reduced glutathione,
      and lipid peroxidation activities were reduced in endophyte-associated plants
      after exposure to 38 degrees C as compared with control and 8 degrees C-treated
      plants. The concentration of saturated fatty acids (palmitic-C16:0; stearic
      C18:0) was lower in endophyte-treated plants with or without low-temperature
      stress, but after 8 degrees C treatment increased compared with controls.
      Unsaturated fatty acids (oleic-C18:1; linoleic-C18:2; linolenic-C18:3 acids) were
      similar at normal conditions; however, at 38 degrees C, C18:2 and C18:3 were
      decreased, and C18:1 was increased in endophyte-treated plants compared with
      controls, while the inverse relationship was found at 8 degrees C. Low levels of
      abscisic acid in P. formosus-associated plants after 38 degrees C treatments
      revealed stress tolerance compared with control and 8 degrees C-treated plants.
      In contrast, salicylic acid was pronounced in endophyte-treated plants after low
      temperature stress as compared to other treatments. The results provide evidence
      that the response to P. formosus association was beneficial at normal growth
      temperature and had varying effects in response to temperature stress.

PMID- 21956659
TI  - Fermentation behavior of osmophilic yeast Candida tropicalis isolated from the
      nectar of Hibiscus rosa sinensis flowers for xylitol production.
AB  - Eighteen yeast species belonging to seven genera were isolated from ten samples
      of nectar from Hibiscus rosa sinensis and investigated for xylitol production
      using D-xylose as sole carbon source. Amongst these isolates, no. 10 was selected
      as the best xylitol producer and identified as Candida tropicalis on the basis of
      morphological, biochemical and 26S rDNA sequencing. C. tropicalis produced 12.11
      gl(-1) of xylitol in presence of 50 gl(-1) of xylose in 72 h at pH 5, 30 degrees
      C and 200 rpm. The strain of C. tropicalis obtained through xylose enrichment
      technique has resulted in a yield of 0.5 gg(-1) with a xylitol volumetric
      productivity of 1.07 gl(-1)h(-1) in the presence of 300 gl(-1) of xylose through
      batch fermentation. This organism has been reported for the first time from
      Hibiscus rosa sinensis flowers. Realizing, the importance of this high valued
      compound, as a sugar substitute, xylose enrichment technique was developed in
      order to utilize even higher concentrations of xylose as substrate for maximum
      xylitol production.

PMID- 21956660
TI  - Unravelling the reaction path of rhodium-MonoPhos-catalysed olefin hydrogenation.
AB  - The mechanism of the asymmetric hydrogenation of methyl (Z)-2-acetamidocinnamate
      (mac) catalysed by [Rh(MonoPhos)(2)(nbd)]SbF(6) (MonoPhos: 3,5-dioxa-4
      phosphacyclohepta[2,1-a:3,4-a']dinaphthalen-4-yl)dimethylamine) was elucidated by
      using (1)H, (31)P and (103)Rh NMR spectroscopy and ESI-MS. The use of nbd allows
      one to obtain in pure form the rhodium complex that contains two units of the
      ligand. In contrast to the analogous complexes that contain cis,cis-1,5
      cyclooctadiene (cod), this complex shows well-resolved NMR spectroscopic signals.
      Hydrogenation of these catalyst precursors at 1 bar total pressure gave rise to
      the formation of a bimetallic complex of general formula
      [Rh(MonoPhos)(2)](2)(SbF(6))(2); no solvate complexes were detected. In the
      dimeric complex both rhodium atoms are ligated to two MonoPhos ligands but, in
      addition, each rhodium atom also binds to one of the binaphthyl rings of a ligand
      that is bound to the other rhodium metal. Upon addition of mac, a mixture of
      diastereomeric complexes [Rh(MonoPhos)(2)(mac)]SbF(6) is formed in which the
      substrate is bound in a chelate fashion to the metal. Upon hydrogenation, these
      adducts are converted into a new complex [Rh(MonoPhos)(2){mac(H)(2)}]SbF(6) in
      which the methyl phenylalaninate mac(H)(2) is bound through its aromatic ring to
      rhodium. Addition of mac to this complex leads to displacement of the product by
      the substrate. No hydride intermediates could be detected and no evidence was
      found for the involvement at any stage of the process of complexes with only one
      coordinated MonoPhos. The collected data suggest that the asymmetric
      hydrogenation follows a Halpern-like mechanism in which the less abundant
      substrate-catalyst adduct is preferentially hydrogenated to phenylalanine methyl
      ester.

PMID- 21956661
TI  - Synthesis, telomerase evaluation and anti-proliferative studies on various series
      of diaminoanthraquinone-linked aminoacyl residue derivatives.
AB  - Four series of compounds containing an anthraquinone-linked moiety and
      symmetrical or asymmetrical aminoacyl residues in side chains at positions 1,4-,
      1,5-, 2,6-, and 2,7- were synthesized and evaluated for their inhibitory effects
      toward telomerase and hTERT expression. Of these, only compound B11 showed
      selective inhibition of telomerase activity. Although it is not as competent as
      several of the anthraquinones we identified previously, nevertheless, the result
      is consistent with that the general structure moiety at the 1,5-position of
      diaminoanthraquinone-linked compound is important for the telomerase inhibitory
      activity. Interestingly, compounds A6, A8, C8, and D8 exhibited selective
      repressing activities toward hTERT expression and showed less effect toward
      proliferation of the treated cancer cells. Although it is not apparent which
      structure moiety is responsible for the telomerase repression effects of these
      compounds, they could be further developed as potential anti-tumor agents.

PMID- 21956662
TI  - Large-scale synthesis of Bi(2)S(3) nanodots as a contrast agent for in vivo X-ray
      computed tomography imaging.

PMID- 21956663
TI  - Empty sella/pituitary atrophy and endocrine impairments as a consequence of
      radiation and chemotherapy in long-term survivors of childhood leukemia.
AB  - Radiation-induced empty sella (ES) or pituitary atrophy/small pituitary and
      endocrine impairments, including pituitary and gonadal dysfunction, can manifest
      decades after radiation and chemotherapy in childhood-onset leukemia patients who
      received prophylactic cranial irradiation or total body irradiation in
      preparation for bone marrow transplant. Six childhood-onset leukemia patients
      (age at diagnosis of leukemia; 2.7-10.2 years) participated in this study.
      Magnetic resonance imaging (MRI) of the pituitary gland and endocrinological
      studies were performed 10.5-32.1 years after cranial irradiation. In four of the
      six patients examined, ES or pituitary atrophy was detected approximately 10.5
      19.8 years after cranial irradiation. Four patients had hypogonadism (primary, 3;
      hypothalamic-pituitary, 1) and one had primary hypothyroidism. We conclude that
      ES or pituitary atrophy and endocrine impairments can manifest decades after
      radiation and chemotherapy in childhood-onset leukemia. These patients should,
      therefore, undergo regular follow-up, including pituitary MRI and hormonal
      examinations.

PMID- 21956664
TI  - Linking landscape history and dispersal traits in grassland plant communities.
AB  - Dispersal limitation and long-term persistence are known to delay plant species'
      responses to habitat fragmentation, but it is still unclear to what extent
      landscape history may explain the distribution of dispersal traits in present-day
      plant communities. We used quantitative data on long-distance seed dispersal
      potential by wind and grazing cattle (epi- and endozoochory), and on persistence
      (adult plant longevity and seed bank persistence) to quantify the linkages
      between dispersal and persistence traits in grassland plant communities and
      current and past landscape configurations. The long-distance dispersal potential
      of present-day communities was positively associated with the amounts of
      grassland in the historical (1835, 1938) landscape, and with a long continuity of
      grazing management-but was not associated with the properties of the current
      landscape. The study emphasises the role of history as a determinant of the
      dispersal potential of present-day grassland plant communities. The importance of
      long-distance dispersal processes has declined in the increasingly fragmented
      modern landscape, and long-term persistent species are expected to play a more
      dominant role in grassland communities in the future. However, even within highly
      fragmented landscapes, long-distance dispersed species may persist locally
      delaying the repayment of the extinction debt.

PMID- 21956665
TI  - Characterization of the microbial community in a partial nitrifying sequencing
      batch biofilm reactor.
AB  - A lab-scale partial nitrifying sequencing batch biofilm reactor was a successful
      start-up. Denaturing gradient gel electrophoresis (DGGE) was used to investigate
      the bacterial community dynamics in three periods together with inocula sludge at
      ambient temperature. The DGGE profiles of bacteria and Shannon-Wiener index (H')
      results showed that high free ammonia (FA) concentration referred to lower
      diversity in the bioreactor system. Cluster analysis indicated that microorganism
      in period III was similar with inocula sludge and was different from that in
      periods I and II. Similar results also appeared in ammonia-oxidizing bacteria
      (AOB) community structure and nitrite-oxidizing bacteria (NOB) community
      structure, and at least four AOB species and two NOB species were present in
      period III, respectively. Phylogenetic analysis of amoA gene sequences showed
      that Nitrosomonas eutropha cluster was predominant in all the three periods. With
      lower ammonium loads, three new operational taxonomic units formed and consisted
      Nitrosomonas sp. Cluster. This article demonstrated that microbial community,
      AOB, and NOB diversity were related with FA concentration closely at ambient
      temperature.

PMID- 21956666
TI  - Genetic and pathogenic variability of Indian strains of Xanthomonas campestris
      pv. campestris causing black rot disease in crucifers.
AB  - Xanthomonas campestris pv. campestris (Pammel) Dowson (Xcc) causing black rot of
      crucifers is a serious disease in India and causes >50% crop losses in favorable
      environmental conditions. Pathogenic variability of Xcc, X. oryzae pv. oryzae
      (Xoo), and X. axonopodis pv. citri (Xac) were tested on 19 cultivars of
      cruciferae including seven Brassica spp. viz., B. campestris, B. carinata, B.
      juncea, B. napus, B. nigra, B. oleracea and B. rapa, and Raphanus sativus for two
      consecutive years viz., 2007-2008 and 2008-2009 under field conditions at Indian
      Agricultural Research Institute, New Delhi. Xcc (22 strains) and other species of
      Xanthomonas (2 strains), they formed three distinct groups of pathogenic
      variability i.e., Group 1, 2, and 3 under 50% minimum similarity coefficient. All
      strains of Xcc clustered under Groupl except Xcc-C20. The strains of Xcc further
      clustered in 6 subgroups viz., A, B, C, D, E, and F based on diseases reaction on
      host. Genetic variability of 22 strains of Xcc was studied by using Rep-PCR (REP
      , BOX- and ERIC-PCR) and 10 strains for hrp (hypersensitive reaction and
      pathogenecity) gene sequence analysis. Xcc strains comprised in cluster 1, Xac
      under cluster 2, while Xoo formed separate cluster 3 based on >50% similarity
      coefficient. Cluster 1 was further divided into 8 subgroups viz., A, B, C, D, E,
      F, G, and H at 75% similarity coefficient. The hrpF gene sequence analysis also
      showed distinctness of Xcc strains from other Xanthomonads. In this study,
      genetic and pathogenic variability in Indian strains of Xcc were established,
      which will be of immense use in the development of resistant genotypes against
      this bacterial pathogen.

PMID- 21956667
TI  - Mitogen-activated protein kinase phosphatase-1 expression in macrophages is
      controlled by lymphocytes during macrophage activation.
AB  - The viewpoints on the control of innate immune cells by the adaptive immune
      system during sepsis remain controversial. Mitogen-activated protein kinase
      phosphatase-1 (MKP-1) is essential to the negative control of innate immunity and
      suppresses the activation of macrophages by inhibiting activated mitogen
      activated protein kinase (MAPK). The purpose of the current study was to observe
      inflammatory response and macrophage activation in mice with severe combined
      immunodeficiency (SCID) with endotoxemia and to determine the role of MKP-1 in
      the control of macrophage activation by the adaptive immune system. Endotoxemia
      was induced in wild-type and SCID mice by an intraperitoneal injection of
      lipopolysaccharide (LPS), and all of the SCID mice died. SCID mice produced more
      inflammatory cytokines than BALB/c mice systemically and locally. TNF-alpha mRNA
      expression was higher and MKP-1 mRNA expression was lower in peritoneal
      macrophages (PMa) from SCID mice compared to PMa from wild-type mice after and
      even before LPS injection. Thioglycollate-stimulated PMa from wild-type mice were
      stimulated with LPS in vitro in the presence or absence of pan-T cells. The
      levels of TNF-alpha and IL-6 were higher in the supernatants from PMa cultured
      alone compared to PMa co-cultured with pan-T cells, and PMa MKP-1 mRNA and
      protein expression were higher when PMa were co-cultured with pan-T cells.
      Therefore, pan-T cells can up-regulate MKP-1 expression in macrophages and
      inhibit the secretion of inflammatory cytokines secretion by macrophages. In SCID
      mice, lymphocyte deficiency, especially T cell deficiency, causes insufficient
      MKP-1 expression in macrophages, which can be responsible for the severe
      inflammation and bad prognosis of septic SCID mice. MKP-1 plays an important role
      in the control of macrophage activation by the adaptive immune system.

PMID- 21956668
TI  - CD4+ Foxp3+ regulatory T cells suppress gammadelta T-cell effector functions in a
      model of T-cell-induced mucosal inflammation.
AB  - CD4(+) CD25(+) Foxp3(+)  regulatory T (T(REG) ) cells are critical mediators of
      peripheral immune tolerance, and abrogation of their function provokes a variety
      of autoimmune and inflammatory states including inflammatory bowel disease. In
      this study, we investigate the functional dynamics of T(REG) -cell responses in a
      CD4(+)  T-cell-induced model of intestinal inflammation in alphabeta T-cell
      deficient (TCR-beta(-/-) ) hosts to gain insights into the mechanism and cellular
      targets of suppression in vivo. We show that CD4(+)  T effector cell transfer
      into T-cell-deficient mice rapidly induces mucosal inflammation and colitis
      development, which is associated with prominent Th1 and Th17 responses.
      Interestingly, we unveil a prominent role for resident gammadelta T cells in
      mucosal inflammation as they promote Th1 and particularly Th17 responses in the
      early phase of inflammation, thus exacerbating colitis development. We further
      demonstrate that CD4(+) CD25(+) Foxp3(+)  T(REG)  cells readily inhibit these
      responses and mediate disease protection, which correlates with their
      accumulation in the draining LN and lamina propria. Moreover, T(REG)  cells can
      directly suppress gammadelta T-cell expansion and cytokine production in vitro
      and in vivo, suggesting a pathogenic role of gammadelta T cells in intestinal
      inflammation. Thus, functional alterations in T(REG)  cells provoke dysregulated
      CD4(+)  and gammadelta T-cell responses to commensal antigens in the intestine.

PMID- 21956669
TI  - Endogenous nitric oxide formation correlates negatively with circulating matrix
      metalloproteinase (MMP)-2 and MMP-9 levels in black subjects.
AB  - Deficient formation of endogenous nitric oxide (NO) contributes to cardiovascular
      diseases, and this may be associated with increased circulating levels of matrix
      metalloproteinase-9 (MMP-9), as previously shown in white subjects. Because
      interethnic differences exist with respect to risk factors, prevalence, and
      severity of cardiovascular diseases, we designed this study to examine whether
      the circulating levels of nitrites (a marker of endogenous NO formation) are
      associated with the plasma levels of MMP-9 and MMP-2 in healthy black subjects.
      We studied 198 healthy subjects self-reported as blacks not taking any
      medications. Venous blood samples were collected and plasma and whole blood
      nitrite levels were measured using an ozone-based chemiluminescence assay. Plasma
      MMP-2 and MMP-9 levels were determined by gelatin zymography. We found a positive
      correlation between plasma MMP-9 and MMP-2 levels (P < 0.0001, rs = 0.556).
      Interestingly, we found a negative relationship between the plasma MMP-9 levels
      and the plasma or whole blood nitrites levels (P = 0.04, rs = -0.149; and P <
      0.0001, rs = -0.349, respectively). In parallel, we found similar negative
      relationships between plasma MMP-2 levels and plasma or whole blood nitrites
      levels (P = 0.02, rs = -0.172; and P < 0.0001, rs = -0.454, respectively). This
      is the first study to show that endogenous nitric oxide formation correlates
      negatively with the circulating levels of both MMP-2 and MMP-9 in black subjects.
      Our findings suggest a mechanistic link between deficient NO formation and
      increased MMPs levels, which may promote cardiovascular diseases.

PMID- 21956670
TI  - Time-sequential modulation in expression of growth factors from platelet-rich
      plasma (PRP) on the chondrocyte cultures.
AB  - Platelets are involved in hemostasis, wound healing, and tumor growth. Autologous
      blood products are commonly used to facilitate healing in a variety of clinical
      surgery applications. Recently, it was shown that platelet-rich plasma (PRP) has
      more specific growth factors that participate in the healing process. This study
      investigated the expression of PRP growth factors and evaluated their potential
      role in the cartilage regeneration using primary isolated chondrocytes. PRP
      obtained from New Zealand White rabbit by low speed centrifugation. Extracted
      PRPs contained 6-10 * 10(6) platelet/MUl and concentration of platelets was
      slightly variable. Primary isolated chondrocytes from the same rabbits were
      cultured and treated with 0.1-20% PRP. The cells were collected and examined by
      reverse transcription-polymerase chain reaction and cytochemical staining. The
      expression of sex determining region Y-box 9, transforming growth factor-beta,
      vascular endothelial growth factor, and chondromdulin-I was increased in
      chondrocyte cultures with 10% PRP by time-dependent manner. To maintain the
      integrity of the cartilage, the proteoglycan contents were also up-regulated from
      the mRNA of aggrecan and positive Safranin-O staining in PRP concentration- and
      time-dependent manner. PRP provides crucial growth factors related to chondrocyte
      proliferation and differentiation through time-sequential modulation. Controlled
      in vivo trials for cartilage regeneration are needed.

PMID- 21956671
TI  - Clostridium butyricum activates TLR2-mediated MyD88-independent signaling pathway
      in HT-29 cells.
AB  - Oral administration of Clostridium butyricum as probiotic is increasingly gaining
      importance in the treatment of diarrhea and the improvement of animal
      performance. However, the mechanisms of host cell receptor recognition of C.
      butyricum and the downstream immune signaling pathways leading to these benefits
      remain unclear. The objective of this study was to analyze the mechanisms
      involved in C. butyricum induction of the toll-like receptor (TLR) signaling.
      Knockdown of myeloid differentiation primary response protein 88 (MyD88)
      expression using small interfering RNA in this manner did not affect C. butyricum
      induced elevated levels of nuclear factor kappaB (NF-kappaB), interleukin-8 (IL
      8), IL-6, and tumor necrosis factor alpha (TNF-alpha), suggesting a MyD88
      independent route to TLR signaling transduction. However, a significant reduction
      in the levels of NF-kappaB, IL-8, IL-6, and TNF-alpha was evident in the absence
      of TLR2 expression, implying the need for TLR2 in C. butyricum recognition.
      Hence, C. butyricum activates TLR2-mediated MyD88-independent signaling pathway
      in human epithelial cells, which adds to our understanding of the molecular
      mechanisms of this probiotic action on gut epithelium.

PMID- 21956672
TI  - Norcantharidin, a protective therapeutic agent in renal tubulointerstitial
      fibrosis.
AB  - Progressive renal tubulointerstitial fibrosis is a common final pathway of nearly
      all forms of chronic kidney disease. Many efforts have been done to arrest or
      prevent renal tubulointerstitial fibrosis but with little progress. Nowadays, few
      therapeutic agents are available in clinical use. Norcantharidin (NCTD) is of
      great benefit in anticancer treatment, by inducing cell apoptosis, inhibiting
      cell proliferation, in addition, blocking tumor metastasis and angiogenesis in
      cancer, whereas little attention is given to its relationship with other
      diseases. Our recent studies demonstrated that NCTD was protective against renal
      tubulointerstitial fibrosis both in vivo and in vitro. The underlying mechanisms
      may include modulation of TGF-beta1/Smad signal cascade, inhibition of protein
      serine/threonine phosphatases (PPP) as well as NF-kappaB. NCTD may be a promising
      therapeutic agent for renal tubulointerstitial fibrosis. In the present article,
      we will review the action of NCTD in renal tubulointerstitial fibrosis and
      discuss its possible mechanisms.

PMID- 21956673
TI  - A microfluidic platform for pharmaceutical salt screening.
AB  - We describe a microfluidic platform comprised of 48 wells to screen for
      pharmaceutical salts. Solutions of pharmaceutical parent compounds (PCs) and salt
      formers (SFs) are mixed on-chip in a combinatorial fashion in arrays of 87.5
      nanolitre wells, which constitutes a drastic reduction of the volume of PC
      solution needed per condition screened compared to typical high throughput
      pharmaceutical screening approaches. Nucleation and growth of salt crystals is
      induced by diffusive and/or convective mixing of solutions containing,
      respectively, PCs and SFs in a variety of solvents. To enable long term
      experiments, solvent loss was minimized by reducing the thickness of the
      absorptive polymeric material, polydimethylsiloxane (PDMS), and by using solvent
      impermeable top and bottom layers. Additionally, well isolation was enhanced via
      the incorporation of pneumatic valves that are closed at rest. Brightfield and
      polarized light microscopy and Raman spectroscopy were used for on-chip analysis
      and crystal identification. Using a gold-coated glass substrate and minimizing
      the thickness of the PDMS control layer drastically improved the signal-to-noise
      ratio for Raman spectra. Two drugs, naproxen (acid) and ephedrine (base), were
      used for validation of the platform's ability to screen for salts. Each PC was
      mixed combinatorially with potential SFs in a variety of solvents. Crystals were
      visualized using brightfield polarized light microscopy. Subsequent on-chip
      analyses of the crystals with Raman spectroscopy identified four different
      naproxen salts and five different ephedrine salts.

PMID- 21956675
TI  - Methodological issues in the assessment of diabetes treatment adherence.
AB  - Improving treatment adherence in patients with diabetes remains an important
      objective of behavioral science research. However, progress is often limited by
      the heterogeneity in methods used to measure treatment adherence and difficulties
      in generalizing across methodologies. Various measurement methods are often used
      with little attention paid to questions regarding validity. Doubts about validity
      of adherence measurement often lead investigators to measure distal clinical
      outcomes instead, such as glycemic control, resulting in a loss of information.
      This article provides an overview of the literature on diabetes medication
      adherence, with a focus on measurement issues. We also consider work conducted in
      other chronic illnesses, particularly HIV/AIDS, that may have value in guiding
      future directions of diabetes medication adherence research. We highlight the
      need for focused investigation on how characteristics of self-report
      methodologies affect the validity of patient responses and conclude with
      practical recommendations based on the current state of the science.

PMID- 21956676
TI  - Building a pipeline of training for behavioral diabetes researchers and
      clinicians: a call for national dialogue.
AB  - In the context of a diabetes epidemic and health care workforce crisis in the
      United States, a national dialogue is needed to identify the pathways and
      mechanisms for training a cohort of behavioral diabetes researchers and
      clinicians. Over the past 40 years, the field of behavioral diabetes in the
      United States has emerged from a coalition of individual clinicians and
      researchers to a specialty field. At present, additional strategies are needed to
      expand the workforce to keep pace with the increasing prevalence of diabetes and
      the changing demographic trends. We review the training resources currently
      available and outline the challenges to trainees at all stages of career
      development. Recommendations include the following: establishing a Task Force for
      Behavioral Diabetes Training and Professional Development charged with the
      creation of a national database of researchers and the development of a training
      model for this interdisciplinary field; creating a national, collaborative
      training network; and increasing the number of funding mechanisms for all
      professionals in behavioral diabetes.

PMID- 21956677
TI  - Mandibular advancement splints for the treatment of sleep apnea syndrome.
AB  - Oral devices, in particular Mandibular Advancement Splints (MAS), which hold the
      mandible in a protruded position during sleep, are increasingly used for the
      treatment of Obstructive Sleep Apnoea (OSA). These devices can be effective in
      treating OSA across a range of severity. Complete resolution of OSA (Apnoea
      Hypopnoea Index [AHI] reduced <5/hr) with use of an MAS occurs in around 40% of
      patients. Overall two thirds of patients experience some clinical benefit (>=50%
      AHI reduction AHI) however others will not objectively respond to this form of
      treatment, despite improvement in symptoms. Although MAS are less efficacious in
      reducing polysomnographic indices of OSA than the standard treatment, Continuous
      Positive Airway Pressure (CPAP), improvements in health outcomes appear to be
      comparable. Therefore, the superiority of CPAP in improving oxygen desaturations
      and reducing AHI may be extenuated by its low compliance, resulting in both
      treatments having similar effectiveness in clinical practice. MAS are now
      recommended as a first line treatment for mild to moderate OSA, as well as in
      more severe patients who are unable to tolerate or refuse CPAP. Success with MAS
      treatment has been associated with factors such as female gender, younger age,
      supine-dependent OSA, lower BMI, smaller neck circumference and craniofacial
      factors, however a reliable, validated method for prediction in the clinical
      setting has yet to be established. MAS are well tolerated, however short-term
      side effects are common although generally minor and transient. Long-term dental
      changes are for the most part subclinical, but can be problematic for a minority
      of patients. MAS are a dental-based treatment for a medical sleep disorder and,
      as such, an interdisciplinary care model is considered important for the
      attainment of optimal patient outcomes.

PMID- 21956678
TI  - [Implantable hearing aids].
AB  - Strictly speaking, implantable hearing aids are technical systems that process
      audiological signals and convey these by direct mechanical stimulation of the
      ossicular chain or cochlea. They have certain benefits over conventional hearing
      aids in terms of wearing comfort and general acceptance. As current studies lack
      convincing audiological results, the indications for implantable hearing aids are
      primarily of medical or cosmetic nature. To date, three systems are available in
      Germany: Vibrant Soundbridge(r), Carina(r), and Esteem(r). Because the
      performance of the different implantable and nonimplantable hearing systems
      together with various surgical procedures are currently undergoing major changes,
      audiological indications may also develop in the future.

PMID- 21956679
TI  - [Update on HPV-induced oropharyngeal cancer].
AB  - Oropharyngeal squamous cell carcinoma (OSCC) is associated with oncogenic human
      papillomavirus (HPV) infection in 30-40% of all cases in Germany. The use of PCR
      and / or in situ hybridisation to detect HPV in tumour tissue is used in
      combination with p16 immunohistochemistry to reliably distinguish HPV-related and
      HPV-unrelated OSCC. The distinct biological behaviour of the HPV-related subset
      of OSCC results in a more favourable prognosis. This might be the result of a
      greater response to chemotherapy and radiotherapy as seen in recent studies.
      Ongoing and future clinical trials will stratify for HPV status. If the results
      of these prospective, randomized trials are consistent with the preliminary
      results of recent studies, HPV status will be of enormous clinical relevance in
      the future.

PMID- 21956680
TI  - Changing to interleaving stimulation might improve dystonia in cases not
      responding to pallidal stimulation.

PMID- 21956681
TI  - Y chromosome losses are exceedingly rare in prostate cancer and unrelated to
      patient age.
AB  - BACKGROUND: Loss of the Y chromosome is a frequently reported chromosomal
      abnormality in many tumor types. This study was undertaken to investigate the
      frequency of Y chromosome losses and this chromosomal abnormality might play a
      potential role in prostate cancer. METHODS: A preexisting prostate cancer tissue
      microarray (TMA) containing samples of 3,261 patients treated by radical
      prostatectomy with clinical follow-up data was used in this study. TMA sections
      were analyzed by fluorescence in situ hybridization (FISH) using a dual labeling
      probe for the centromeres of the X and Y chromosome. RESULTS: Unequivocal losses
      of the Y chromosome were seen in only 12 of 2,053 analyzable cases. No
      significant associations were found between Y loss and patient age, pT stage, and
      the risk of PSA recurrence. Interestingly, in our study the presence of Y losses
      was significantly associated with high Gleason grade (P = 0.0034). CONCLUSIONS:
      Loss of the Y chromosome is a rare event in prostate cancer. Y losses occur in
      much higher rates in most other cancer types. For this reason, we suggest that
      the expression of at least one Y chromosome gene is essential for prostate
      epithelial cells and it is possible that such a gene could represent a suitable
      target for future therapy of prostate cancer.

PMID- 21956682
TI  - A road toward the future of nursing: paving the way with trust, collaboration,
      and strategic alliances.

PMID- 21956683
TI  - Performance pedagogy in nursing.

PMID- 21956684
TI  - A case of hypophosphatemic osteomalacia secondary to deferasirox therapy.
AB  - Patients with beta-thalassemia major require iron-chelation therapy to avoid the
      complication of iron overload. Until recently, deferoxamine (DFO) was the major
      iron chelator used in patients requiring chronic hypertransfusion therapy, but
      DFO required continuous subcutaneous therapy. The availability of deferasirox
      (Exjade(r)), an orally active iron chelator, over the past 4 years represented a
      necessary alternative for patients requiring chelation therapy. However, there
      have been increasing reports of proximal renal tubular dysfunction and Fanconi
      syndrome associated with deferasirox in the literature. We report a case of
      hypophosphataemic osteomalacia secondary to deferasirox therapy.

PMID- 21956685
TI  - D,L-sulforaphane-induced apoptosis in human breast cancer cells is regulated by
      the adapter protein p66Shc.
AB  - Cancer chemopreventive response to D,L-sulforaphane (SFN), a synthetic racemic
      analogue of broccoli constituent L-sulforaphane, is partly attributable to
      apoptosis induction, but the mechanism of cell death is not fully understood. The
      present study demonstrates a critical role for adapter protein p66(Shc) in SFN
      induced apoptosis. Immortalized mouse embryonic fibroblasts (MEF) derived from
      p66(shc) knockout mice were significantly more resistant to SFN-induced
      apoptosis, collapse of mitochondrial membrane potential, and reactive oxygen
      species (ROS) production compared with MEF obtained from the wild-type mice.
      Notably, a spontaneously immortalized and non-tumorigenic human mammary
      epithelial cell line (MCF-10A) was resistant to SFN-induced ROS production and
      apoptosis. Stable overexpression of manganese superoxide dismutase in MCF-7 and
      MDA-MB-231 human breast cancer cells conferred near complete protection against
      SFN-induced apoptosis and mitochondrial membrane potential collapse. SFN
      treatment resulted in increased S36 phosphorylation and mitochondrial
      translocation of p66(shc) in MDA-MB-231 and MCF-7 cells, and SFN-induced
      apoptosis was significantly attenuated by RNA interference of p66(shc) in both
      cells. SFN-treated MDA-MB-231 and MCF-7 cells also exhibited a marked decrease in
      protein level of peptidyl prolyl isomerase (Pin1), which is implicated in
      mitochondrial translocation of p66(shc) . However, stable overexpression of Pin1
      failed to alter proapoptotic response to SFN at least in MCF-7 cells. Finally,
      SFN-induced S36 phosphorylation of p66(Shc) was mediated by protein kinase Cbeta
      (PKCbeta), and pharmacological inhibition of PKCbeta significantly inhibited
      apoptotic cell death resulting from SFN exposure. In conclusion, the present
      study provides new insight into the mechanism of SFN-induced apoptosis involving
      PKCbeta -mediated S36 phosphorylation of p66(shc).

PMID- 21956686
TI  - Aldehyde cruciforms: dosimeters for primary and secondary amines.
AB  - We demonstrate that aldehyde-substituted donor-acceptor cruciforms [1,4
      bis(arylethynyl)-2,5-distyrylbenzenes] are useful dosimeters for primary amines,
      primary diamines, and secondary amines. The 1,n-diamines are particularly
      reactive towards this dosimeter and can be detected in less than 100 ppm
      concentration. Using a single aldehyde-functionalized cruciform in seven
      different solvents allowed us to discern fourteen different amines by digital
      photography and statistical evaluation of the response patterns extracted as red,
      green, blue (RGB) values.

PMID- 21956687
TI  - Artificial microRNA interference targeting AT(1a) receptors in paraventricular
      nucleus attenuates hypertension in rats.
AB  - Excessive sympathetic activity has a crucial role in the initiation and
      progression of chronic structural alterations in the heart and vessels associated
      with hypertension. Angiotensin II type 1a receptors (AT(1a)R) in paraventricular
      nucleus (PVN) are involved in sympathetic overdrive and hypertension. The present
      study was designed to investigate the cardiovascular beneficial effects of the
      AT(1a)R gene silence in the PVN in hypertension. The PVN microinjection of
      recombinant adenoviral vectors expressing either artificial microRNA (amiRNA)
      targeting AT(1a) receptors (Ad-miR-AT(1a)) or control microRNA (Ad-miR-Con) were
      carried out in spontaneously hypertensive rats (SHR) and normotensive Wistar
      rats. The vectors were labels with green fluorescent protein (GFP). The
      successful amiRNA interference was confirmed by the AT(1) receptors reduction and
      the GFP expression in the PVN. Significant depressor effects were observed from
      day 5 to day 20 after Ad-miR-AT(1a) treatment in SHR. Ad-miR-AT(1a) treatment
      decreased the ratio of left ventricular weight to body weight, cross-sectional
      areas of myocytes, myocardial fibrosis, media thickness, and the media/lumen
      ratio of the aorta and the mesenteric artery in SHR. The amiRNA interference
      reduced the basal sympathetic activity, cardiac sympathetic afferent reflex,
      plasma norepinephrine and plasma angiotensin II in SHR. These results indicate
      that amiRNA interference targeting AT(1a)R in the PVN decreases arterial blood
      pressure, blunts sympathetic activity and improves myocardial and vascular
      remodeling in SHR.

PMID- 21956688
TI  - Tumor vasculature is a key determinant for the efficiency of nanoparticle
      mediated siRNA delivery.
AB  - Delivering small interfering RNA (siRNA) to tumors using clinically viable
      formulations remains the primary technical hurdle that prevents the development
      of siRNA therapy for cancer treatment. Over the past several years, significant
      effort has been devoted to explore novel delivery strategies, whereas relatively
      little attention has been paid to understand the impact of physiological
      constrains such as tumor vasculature on the efficiency of siRNA delivery. Using
      the previously described positive-readout tumor models where successful siRNA
      delivery leads to an upregulation of beta-galactosidase within tumor sections, we
      analyzed the spatial distribution of localized target knockdown within tumor
      sections relative to tumor hypoxia and found that stable nucleic acid lipid
      particle (SNALP), a lipid nanoparticle-based delivery system, predominantly
      delivers siRNA to areas adjacent to functional tumor blood vessels. Increasing
      tumor vascularity by ectopic expression of VEGF resulted in more efficient siRNA
      delivery to tumors using SNALP. SNALP-mediated delivery of a siRNA-targeting Ran
      GTPase led to target knockdown and significant antitumor efficacy in the highly
      vascularized HepG2-derived liver tumors, but not in the poorly vascularized HCT
      116-derived liver tumors. These results highlight the significant impact of tumor
      vasculature on siRNA delivery and call for a more focused effort on addressing
      tumor penetration after extravasation, an area of only limited attention
      currently.

PMID- 21956689
TI  - Mtb32 is a promising tuberculosis antigen for DNA vaccination in pre- and post
      exposure mouse models.
AB  - Identification of antigens that provide protective immunity via prophylactic and
      therapeutic vaccination against Mycobacterium tuberculosis is critical for the
      development of subunit vaccines for tuberculosis (TB). In this study, we
      performed a head-to-head comparison of seven well-known TB antigens delivered by
      DNA vaccine, and evaluated their respective immunogenicities and protective
      efficacies in pre- and post-exposure mouse models. All TB antigens were designed
      as a chimeric fusion with Flt3-L to enhance antigen-specific T-cell immunity upon
      vaccination. Prophylactic vaccination with the Flt3L (F)-Mtb32 DNA vaccine
      elicited significant protection in both the spleen and lungs against M.
      tuberculosis challenge, comparable to the Bacillus Calmette-Guerin vaccine. F
      Ag85A and F-Mtb32 DNA vaccines, in combination with chemotherapy, reduced the
      bacterial burden to undetectable levels in the lungs of all mice infected with M.
      tuberculosis. These data collectively indicate that the F-Mtb32 DNA vaccine
      confers the most efficient protective immunity that suppresses bacterial growth
      in the active or latent status of M. tuberculosis.

PMID- 21956690
TI  - Current progress in the development of RNAi-based therapeutics for HIV-1.
AB  - Highly active antiretroviral therapy (HAART) treatment for HIV has changed the
      course of AIDS in societies in which the drugs are readily available. Despite the
      great success of HAART, drug resistance and toxicity issues still remain a
      concern for some individuals. Thus, a number of investigators have been exploring
      other approaches for inhibiting HIV-1 replication. One of the most potent of
      these is the use of RNA interference (RNAi). This review will focus solely on the
      use of RNAi for the treatment of HIV-1 infection, including the problems,
      progress and future prospects.

PMID- 21956691
TI  - Nonviral gene delivery of erythropoietin by mesenchymal stromal cells.
AB  - Erythropoietin (EPO) acts on erythroblasts in the bone marrow (BM) to stimulate
      the formation of red blood cells. In this study, we wanted to determine whether
      BM-derived mesenchymal stromal cells (MSCs) can be used as cellular vehicles to
      deliver EPO in mice without the use of viral vectors. After isolation and
      characterization of murine MSCs (mMSCs), different transient transfection
      procedures were compared for their efficacy of gene transfer of the pEGFP-N2
      plasmid. Nucleofection outperformed magnetofection and lipofection. Stably
      transfected mMSCs were generated by selection with G418-disulfate and single-cell
      colony-forming unit (sc-CFU) assays without changes in their proliferation
      capacity and osteogenic/adipogenic differentiation potential. Next, murine EPO
      was stably introduced into mMSCs by nucleofection of a plasmid encoding the epo
      and egfp genes. Intraperitoneal transplantation of EPO-expressing mMSCs increased
      serum EPO levels, hematocrit and hemoglobin of C57BL/6 mice within 1 week. The
      hematocrit remained elevated for 5 weeks, but production of antibodies against
      both transgenes was detected in the hosts and serum EPO levels normalized. Our
      results suggest that nonviral gene delivery into MSCs can be used to enhance the
      known beneficial effects MSCs by additional production of therapeutic factors
      like EPO in vivo.

PMID- 21956692
TI  - Novel random peptide libraries displayed on AAV serotype 9 for selection of
      endothelial cell-directed gene transfer vectors.
AB  - We have demonstrated the potential of random peptide libraries displayed on adeno
      associated virus (AAV)2 to select for AAV2 vectors with improved efficiency for
      cell type-directed gene transfer. AAV9, however, may have advantages over AAV2
      because of a lower prevalence of neutralizing antibodies in humans and more
      efficient gene transfer in vivo. Here we provide evidence that random peptide
      libraries can be displayed on AAV9 and can be utilized to select for AAV9 capsids
      redirected to the cell type of interest. We generated an AAV9 peptide display
      library, which ensures that the displayed peptides correspond to the packaged
      genomes and performed four consecutive selection rounds on human coronary artery
      endothelial cells in vitro. This screening yielded AAV9 library capsids with
      distinct peptide motifs enabling up to 40-fold improved transduction efficiencies
      compared with wild-type (wt) AAV9 vectors. Incorporating sequences selected from
      AAV9 libraries into AAV2 capsids could not increase transduction as efficiently
      as in the AAV9 context. To analyze the potential on endothelial cells in the
      intact natural vascular context, human umbilical veins were incubated with the
      selected AAV in situ and endothelial cells were isolated. Fluorescence-activated
      cell sorting analysis revealed a 200-fold improved transduction efficiency
      compared with wt AAV9 vectors. Furthermore, AAV9 vectors with targeting sequences
      selected from AAV9 libraries revealed an increased transduction efficiency in the
      presence of human intravenous immunoglobulins, suggesting a reduced
      immunogenicity. We conclude that our novel AAV9 peptide library is functional and
      can be used to select for vectors for future preclinical and clinical gene
      transfer applications.

PMID- 21956693
TI  - CD22 serves as a receptor for soluble IgM.
AB  - CD22 (Siglec-2) is a B-cell membrane-bound lectin that recognizes glycan ligands
      containing alpha2,6-linked sialic acid (alpha2,6Sia) and negatively regulates
      signaling through the B-cell Ag receptor (BCR). Although CD22 has been
      investigated extensively, its precise function remains unclear due to acting
      multiple phases. Here, we demonstrate that CD22 is efficiently activated in trans
      by complexes of Ag and soluble IgM (sIgM) due to the presence of glycan ligands
      on sIgM. This result strongly suggests sIgM as a natural trans ligand for CD22.
      Also, CD22 appears to serve as a receptor for sIgM, which induces a negative
      feedback loop for B-cell activation similar to the Fc receptor for IgG
      (FcgammaRIIB).

PMID- 21956694
TI  - The doping effect of fluorinated aromatic solvents on the rate of ruthenium
      catalysed olefin metathesis.
AB  - A study concerning the effect of using a fluorinated aromatic solvent as the
      medium for olefin metathesis reactions catalysed by ruthenium complexes bearing N
      heterocyclic carbene ligands is presented. The use of fluorinated aromatic
      hydrocarbons (FAH) as solvents for olefin metathesis reactions catalysed by
      standard commercially available ruthenium pre-catalysts allows substantially
      higher yields of the desired products to be obtained, especially in the case of
      demanding polyfunctional molecules, including natural and biologically active
      compounds. Interactions between the FAH and the second-generation ruthenium
      catalysts, which apparently improve the efficiency of the olefin metathesis
      transformation, have been studied by X-ray structure analysis and computations,
      as well as by carrying out a number of metathesis experiments. The optimisation
      of reaction conditions by using an FAH can be regarded as a complementary
      approach for the design of new improved ruthenium catalysts. Fluorinated aromatic
      solvents are an attractive alternative medium for promoting challenging olefin
      metathesis reactions.

PMID- 21956696
TI  - Severe congenital toxoplasmosis in the United States: clinical and serologic
      findings in untreated infants.
AB  - BACKGROUND: Congenital toxoplasmosis can cause significant neurologic
      manifestations and other untoward sequelae. METHODS: The Palo Alto Medical
      Foundation Toxoplasma Serology Laboratory database was searched for data on
      infants 0 to 180 days old, in whom congenital toxoplasmosis had been confirmed
      and who had been tested for Toxoplasma gondii-specific immunoglobulin G (IgG),
      IgM, and IgA antibodies, between 1991 and 2005. Their clinical findings were
      confirmed at the National Collaborative Chicago-based Congenital Toxoplasmosis
      Study center. We reviewed available clinical data and laboratory profiles of 164
      infants with congenital toxoplasmosis whose mothers had not been treated for the
      parasite during gestation. RESULTS: One or more severe clinical manifestations of
      congenital toxoplasmosis were reported in 84% of the infants and included eye
      disease (92.2%), brain calcifications (79.6%), and hydrocephalus (67.7%). In
      61.6% of the infants, eye disease, brain calcifications, and hydrocephalus were
      present concurrently. T. gondii-specific IgM, IgA, and IgE antibodies were
      demonstrable in 86.6%, 77.4%, and 40.2% of the infants, respectively. Testing for
      IgM and IgA antibodies increased the sensitivity of making the diagnosis of
      congenital toxoplasmosis to 93% compared with testing for IgM or IgA
      individually. IgM and IgA antibodies were still present in 43.9% of infants
      diagnosed between 1 and 6 months of life. CONCLUSIONS: Our study reveals that
      severe clinical signs of congenital toxoplasmosis including hydrocephalus, eye
      disease, or intracranial calcifications occurred in 85% infants whose sera were
      referred to our reference Toxoplasma Serology Laboratory during a period of 15
      years. Laboratory tests, including serologic and polymerase chain reaction tests,
      were critical for diagnosis in the infants. Our results contrast remarkably with
      those of European investigators who rarely observe severe clinical signs in
      infants with congenital toxoplasmosis.

PMID- 21956695
TI  - Dietary oxidative stress and antioxidant defense with an emphasis on plant
      extract administration.
AB  - Eukaryotic cells generally function in a reduced state, but an amount of reactive
      species is essential for several biochemical processes. The antioxidant network
      is the defensive mechanism that occurs when the concentration of reactive species
      exceeds a threshold. Polyphenolic compounds present in plant extracts are potent
      antioxidants in vitro, but they may promote oxidative stress when administered in
      animals and humans, especially when given as supplements in exercise, a modality
      usually adopted as an oxidant stimulus. This is mainly observed when antioxidant
      molecules are administered separately and not as part of a diet. Exercise is
      usually adopted as a physiological model for examining the effects of reactive
      species in human or animal physiology. The use of exercise as a model
      demonstrates that reactive species do not always have adverse effects, but are
      necessary in physiological processes that are beneficial for human health. This
      review summarizes what is known about antioxidant supplementation and
      demonstrates the need for a meticulous examination of the in vitro findings
      before applying them to in vivo models. The term "antioxidant" seems elusive, and
      it is more appropriate to characterize a compound as "antioxidant" if we know in
      which concentration it is used, when it is used, and under which conditions.

PMID- 21956697
TI  - Evaluation of a robotic technique for transrectal MRI-guided prostate biopsies.
AB  - OBJECTIVES: To evaluate the accuracy and speed of a novel robotic technique as an
      aid to perform magnetic resonance image (MRI)-guided prostate biopsies on
      patients with cancer suspicious regions. METHODS: A pneumatic controlled MR
      compatible manipulator with 5 degrees of freedom was developed in-house to guide
      biopsies under real-time imaging. From 13 consecutive biopsy procedures, the
      targeting error, biopsy error and target displacement were calculated to evaluate
      the accuracy. The time was recorded to evaluate manipulation and procedure time.
      RESULTS: The robotic and manual techniques demonstrated comparable results
      regarding mean targeting error (5.7 vs 5.8 mm, respectively) and mean target
      displacement (6.6 vs 6.0 mm, respectively). The mean biopsy error was larger (6.5
      vs 4.4 mm) when using the robotic technique, although not significant. Mean
      procedure and manipulation time were 76 min and 6 min, respectively using the
      robotic technique and 61 and 8 min with the manual technique. CONCLUSIONS:
      Although comparable results regarding accuracy and speed were found, the extended
      technical effort of the robotic technique make the manual technique - currently -
      more suitable to perform MRI-guided biopsies. Furthermore, this study provided a
      better insight in displacement of the target during in vivo biopsy procedures.

PMID- 21956698
TI  - Knee joint anterior malalignment and patellofemoral osteoarthritis: an MRI study.
AB  - OBJECTIVES: To evaluate patellofemoral congruency measurements on MRI and
      correlate the findings with severity of ipsilateral osteoarthritis. METHODS: We
      retrospectively reviewed 650 consecutive knee MRI examinations from 622 patients
      divided into two age groups: <=50 and >50 year-old. The femoral sulcus angle (SA)
      and depth (SD), lateral patellar displacement (LPD), lateral patellofemoral angle
      (LPFA), tibial tubercle-trochlear groove (TT-TG) distance and Insall-Salvati
      index as well as the grade of focal cartilage defects (ranging from I to IV) in
      the patellofemoral region were assessed in each subject on axial and sagittal fat
      saturated intermediate-w MR images. RESULTS: A significant difference exists
      between normal and knees with patellofemoral joint osteoarthritis regarding SA (p
      = 0.0002 and <0.0001), SD (p = 0.0004 and <0.0001), LPD (p = 0.0014 and 0.0009)
      and LPFA (p = 0.0002 and 0.0003) in both age groups (<=50 and >50 respectively).
      Significant correlation was found between grading of cartilage defects and SA
      (rho = 0.21, p = 0.0001 and 0.443, <0.0001), SD (rho = -0.198, p = 0.0003 and 
      0.418, <0.0001), LPD (rho = 0.176, p = 0.0013 and 0.251, 0.0002) and LPFA (rho = 
      0.204, p = 0.0002 and -0.239, 0.0005) in both age groups. CONCLUSIONS: Knee joint
      anterior malalignment is multivariably associated with patellofemoral
      osteoarthritis. KEY POINTS: * MRI is an excellent method to evaluate knee
      alignment and articular cartilage damage. * Significant associations exist
      between alignment parameters and osteoarthritis of the patellofemoral joint. *
      The "sulcus angle" and "sulcus depth" were the most valuable osteoarthritic
      markers.

PMID- 21956699
TI  - Efficacy of urethral catheterisation with a hydrophilic guidewire in patients
      with urethral trauma for treating acute urinary bladder retention after failed
      attempt at blind catheterisation.
AB  - OBJECTIVES: To evaluate the efficacy of urethral catheterisation using a
      hydrophilic guidewire under fluoroscopic guidance in patients with urethral
      trauma after a failed attempt at blind catheterisation. METHODS: A diagnosis of
      urethral trauma was made in 39 cases in 38 men. Patients ranged in age from 41 to
      85 years (mean age, 60 years). Causes of the urethral injuries were iatrogenic
      urethral injury during catheter placement (n = 18), traumatic self-removal of a
      catheter (n = 12), straddle injuries (n = 6) and motor vehicle accidents (n = 3).
      All patients underwent failed blind urethral catheterisation. After
      urethrography, we attempted to insert a hydrophilic guidewire through the urethra
      into the urinary bladder, and then to place a 3-way balloon retention urethral
      catheter into the bladder guided by prior passage of the guidewire under
      fluoroscopy. RESULTS: Of 39 attempts of inserting the urethral catheter into the
      urinary bladder, 34 (87.2%) were successful. Of 5 failures (12.8%), 2 were
      American Association for the Surgery of Trauma (AAST) urethral injury type 3 and
      3 were type 4/5. Among these, there were 3 cases of pseudolumen formation.
      CONCLUSIONS: Hydrophilic guidewire-assisted urethral catheterisation in patients
      with urethral trauma is a safe, simple technique for relieving acute bladder
      retention after a failed attempt at blind catheterisation. KEY POINTS:
      Hydrophilic guidewire-assisted urethral catheterisation is useful following
      failed blind catheterisation. Immediate management of urethral injury is
      important to reduce morbidity. Hydrophilic guidewire-assisted urethral
      catheterisation can be applied immediately after diagnostic urethrography.

PMID- 21956700
TI  - Human enhancement: revisiting the ethical framework.

PMID- 21956701
TI  - Characterization of ubiquitination dependent dynamics in growth factor receptor
      signaling by quantitative proteomics.
AB  - Protein ubiquitination is a dynamic reversible post-translational modification
      that plays a key role in the regulation of numerous cellular processes including
      signal transduction, endocytosis, cell cycle control, DNA repair and gene
      transcription. The conjugation of the small protein ubiquitin or chains of
      ubiquitin molecules of various types and lengths to targeted proteins is known to
      alter proteins' lifespan, localization and function and to modulate protein
      interactions. Despite its central importance in various aspects of cellular life
      and function there are only a limited number of reports investigating
      ubiquitination on a proteomic scale, mainly due to the inherited complexity and
      heterogeneity of ubiquitination. We describe here a quantitative proteomics
      strategy based on the specificity of ubiquitin binding domains (UBDs) and Stable
      Isotope Labeling by Amino acids in Cell culture (SILAC) for selectively decoding
      ubiquitination-driven processes involved in the regulation of cellular signaling
      networks. We applied this approach to characterize the temporal dynamics of
      ubiquitination events accompanying epidermal growth factor receptor (EGFR) signal
      transduction. We used recombinant UBDs derived from endocytic adaptor proteins
      for specific enrichment of ubiquitinated complexes from the EGFR network and
      subsequent quantitative analyses by high accuracy mass spectrometry. We show that
      the strategy is suitable for profiling the dynamics of ubiquitination occurring
      on individual proteins as well as ubiquitination-dependent events in signaling
      pathways. In addition to a detailed seven time-point profile of EGFR
      ubiquitination over 30 minutes of ligand stimulation, our data determined
      prominent involvement of Lysine-63 ubiquitin branching in EGF signaling.
      Furthermore, we found two centrosomal proteins, PCM1 and Azi1, to form a multi
      protein complex with the ubiquitin E3 ligases MIB1 and WWP2 downstream of the
      EGFR, thereby revealing possible ubiquitination cross-talk between EGF signaling
      and centrosomal-dependent rearrangements of the microtubules. This is a general
      strategy that can be utilized to study the dynamics of other cellular systems and
      post-translational modifications.

PMID- 21956702
TI  - Screening for antibodies against intact cancer cells with a naive large phage
      antibody library.
AB  - Large phage antibody libraries are expected to be an efficient technology for
      obtaining humanized anti-tumor antibodies. However, few reports have been
      concerned about the selection strategies for intact cancer cells as targets. In
      this study, a 2x1011 large naive scFv library from blood B lymphocytes of normal
      adult donors and neonatal cord blood was constructed using the LoxP-cre system.
      Three human esophageal cancer cell lines were equally mixed for use as the
      target. These intact cells were divided into two groups, PF and NF, according to
      the treatment method of the cells (fixed with 2% PFA or not, respectively).
      Positive phage antibodies were identified following 4 panning cycles of adhesion,
      elution and amplification. Using a cell ELISA assay, it was found that the
      additional procedure of directly infecting XL1-Blue bacteria with the cell pellet
      following washing with an acidic solution can effectively decrease the loss of
      positive phage, yielding a positive screening rate of 11.6% (61/525). Most of the
      phage antibodies displayed binding activity with all three esophageal cancer cell
      lines. Moreover, other phages (such as NFc53a and NFc70a) appeared to be specific
      for certain cell lines. Regarding the method used to treat the target cells, both
      the positive screening rate and the genetic diversity of the antibody variable
      region were significantly higher in the NF group (12.9 and 71.4%, respectively)
      than in the PF group (10.5 and 14.2%, respectively). Immunohistochemical analysis
      demonstrated that the scFv phages have good specificity for esophageal cancer.
      This technology is helpful for developing small molecular tracers and targeted
      therapies for malignant tumors.

PMID- 21956703
TI  - Copper deficiency in Wilson's disease: an avoidable complication of treatment.

PMID- 21956704
TI  - Diagnosis and antimicrobial therapy of lung infiltrates in febrile neutropenic
      cancer patients.
AB  - Pulmonary infiltrates develop in up to 25% of febrile neutropenic patients and
      are frequently refractory to broad-spectrum antibacterial therapy. Etiologically,
      Aspergillus spp., Pneumocystis jiroveci, multi-resistant Gram-negative rods as
      well as mycobacteria and respiratory viruses may be involved. Taking into account
      the predominant role of fungal pathogens, typically without microbiological
      proof, prompt addition of mold-active systemic antifungal therapy improves
      clinical outcome, while other microorganisms should typically be targeted based
      upon microbiological test results only. Microbial isolates from blood cultures,
      bronchoalveolar lavage or respiratory secretions must be critically interpreted
      with respect to their etiological relevance for pulmonary infiltrates. Non
      culture based diagnostic procedures to detect circulating antigens such as
      galactomannan or 1,3-beta-D-glucan, or PCR techniques to amplify DNA from blood,
      bronchoalveolar lavage or tissue specimens, may facilitate the diagnosis. For pre
      emptive antifungal treatment, voriconazole or liposomal amphotericin B are
      preferred. Antifungal treatment should be continued for at least 14 days before
      non-response and treatment modification are considered. Primary choice for
      treatment of Pneumocystis pneumonia remains high-dose trimethoprim
      sulfamethoxazole, while cytomegalovirus pneumonia is treated with ganciclovir in
      the majority of patients affected.

PMID- 21956705
TI  - Will the increased prevalence of nonalcoholic steatohepatitis (NASH) in the age
      of better hepatitis C virus therapy make NASH the deadlier disease?

PMID- 21956706
TI  - JNK: a double-edged sword in tumorigenesis.

PMID- 21956707
TI  - Border patrol intensifies for hepatitis C virus entry.

PMID- 21956708
TI  - Noninvasive methods for the assessment of liver fibrosis: a window open on the
      future?

PMID- 21956709
TI  - Hepatitis B virus infection: a strong case against ageism.

PMID- 21956710
TI  - Risk of cancer in patients on insulin glargine and other insulin analogues in
      comparison with those on human insulin: results from a large population-based
      follow-up study.
AB  - AIMS/HYPOTHESIS: Several publications suggest an association between certain
      types of insulin and cancer, but with conflicting results. We investigated
      whether insulin glargine (A21Gly,B31Arg,B32Arg human insulin) is associated with
      an increased risk of cancer in a large population-based cohort study. METHODS:
      Data for this study were obtained from dispensing records from community
      pharmacies individually linked to hospital discharge records from 2.5 million
      individuals in the Netherlands. In a cohort of incident users of insulin, the
      association between insulin glargine and other insulin analogues, respectively,
      and cancer was analysed in comparison with human insulin using Cox proportional
      hazard models with cumulative duration of drug use as a time-varying determinant.
      The first hospital admission with a primary diagnosis of cancer was considered as
      the main outcome; secondary analyses were performed with specific cancers as
      outcomes. RESULTS: Of the 19,337 incident insulin users enrolled, 878 developed
      cancer. Use of insulin glargine was associated with a lower risk of malignancies
      in general in comparison with human insulin (HR 0.75, 95% CI 0.71, 0.80). In
      contrast, an increased risk was found for breast cancer (HR 1.58, 95% CI 1.22,
      2.05). Dose-response relationships could not be identified.
      CONCLUSION/INTERPRETATION: Users of insulin glargine and users of other insulin
      analogues had a lower risk of cancer in general than those using human insulin.
      Both associations might be a consequence of residual confounding, lack of
      adherence or competing risk. However, as in previous studies, we demonstrated an
      increased risk of breast cancer in users of insulin glargine in comparison with
      users of human insulin.

PMID- 21956711
TI  - Exenatide decreases hepatic fibroblast growth factor 21 resistance in non
      alcoholic fatty liver disease in a mouse model of obesity and in a randomised
      controlled trial.
AB  - AIMS/HYPOTHESIS: Systemic fibroblast growth factor (FGF)21 levels and hepatic
      FGF21 production are increased in non-alcoholic fatty liver disease patients,
      suggesting FGF21 resistance. We examined the effects of exenatide on FGF21 in
      patients with type 2 diabetes and in a diet-induced mouse model of obesity (DIO).
      METHODS: Type 2 diabetes mellitus patients (n = 24) on diet and/or metformin were
      randomised (using a table of random numbers) to receive additional treatment
      consisting of pioglitazone 45 mg/day or combined therapy with pioglitazone (45
      mg/day) and exenatide (10 MUg twice daily) for 12 months in an open label
      parallel study at the Baylor Clinic. RESULTS: Twenty-one patients completed the
      entire study and were included in the analysis. Pioglitazone treatment (n = 10)
      reduced hepatic fat as assessed by magnetic resonance spectroscopy, despite a
      significant increase in body weight (Delta = 3.7 kg); plasma FGF21 levels did not
      change (1.9  +/-  0.6 to 2.2  +/-  0.6 ng/ml [mean +/- SEM]). However, combined
      pioglitazone and exenatide therapy (n = 11) was associated with a significant
      reduction of FGF21 levels (2.3  +/-  0.5 to 1.1  +/-  0.3 ng/ml) and a greater
      decrease in hepatic fat. Besides weight gain observed in the pioglitazone-treated
      patients, lower extremity oedema was observed as a side effect in two of the ten
      patients. Three patients who received pioglitazone and exenatide combination
      therapy complained of significant nausea that was self-limiting and did not
      require them to leave the study. In DIO mice, exendin-4 for 4 weeks significantly
      reduced hepatic triacylglycerol content, decreased hepatic FGF21 protein and
      mRNA, and enhanced phosphorylation of hepatic AMP-activated protein kinase (AMPK)
      and acetyl-CoA carboxylase, although no significant difference in weight and body
      fat was observed. Hepatic FGF21 correlated inversely with hepatic AMPK
      phosphorylation CONCLUSIONS/INTERPRETATION: In type 2 diabetes mellitus, combined
      pioglitazone and exenatide therapy is associated with a reduction in plasma FGF21
      levels, as well as a greater decrease in hepatic fat than that achieved with
      pioglitazone therapy. In DIO mice, exendin-4 treatment reduces hepatic
      triacylglycerol and FGF21 protein, and enhances hepatic AMPK phosphorylation,
      suggesting an improvement of hepatic FGF21 resistance. TRIAL REGISTRATION NUMBER:
      ClinicalTrials.gov NCT 01432405.

PMID- 21956713
TI  - Effects of three-monthly oral 150,000 IU cholecalciferol supplementation on
      falls, mobility, and muscle strength in older postmenopausal women: a randomized
      controlled trial.
AB  - Daily vitamin D in addition to calcium supplementation reduces falls and
      fractures in older women. However, poor adherence to therapy is a common clinical
      problem. To examine the effects of supervised oral 3-monthly vitamin D therapy on
      falls, muscle strength, and mobility, we conducted a 9-month randomized, double
      blind, placebo-controlled trial in 686 community-dwelling ambulant women aged
      over 70 years. Participants received either oral cholecalciferol 150,000 IU every
      3 months (n = 353) or an identical placebo (n = 333). All participants were
      advised to increase dietary calcium intake. Falls data were collected 3-monthly.
      At baseline, 3, 6, and 9 months, muscle strength was measured by a handheld
      dynamometer and mobility by the Timed Up and Go (TUG) test. Serum 25
      hydroxyvitamin D (25OHD) was measured in a subgroup of 40 subjects. Mean age at
      baseline was 76.7 +/- 4.1 years. The average serum 25OHD value at baseline was
      65.8 +/- 22.7 nmol/L. By 3, 6, and 9 months after supplementation, 25OHD levels
      of the vitamin D group were approximately 15 nmol/L higher than the placebo
      group. Calcium intake did not change significantly between baseline (864 +/- 412
      mg/day) and 9 months (855 +/- 357 mg/day). Faller rates in the two groups did not
      differ: vitamin D group, 102 of 353 (29%); placebo group, 89 of 333 (27%). At 9
      months, compared to placebo or baseline, muscle strength, and TUG were not
      altered by vitamin D. In conclusion, oral cholecalciferol 150,000 IU therapy
      administered 3-monthly had neither beneficial nor adverse effects on falls or
      physical function. These data together with previous findings confirm that
      intermittent large doses of vitamin D are ineffective or have a deleterious
      effect on falls. Thus despite adherence issues with daily vitamin D replacement,
      an intermittent, high-dose vitamin D regimen cannot be supported as a strategy to
      reduce falls and fractures.

PMID- 21956712
TI  - Manipulation of cellular redox parameters for improving therapeutic responses in
      B-cell lymphoma and multiple myeloma.
AB  - Developing novel combined-modality therapeutic approaches based on understanding
      of the involvement of redox biology in apoptosis of malignant cells is a
      promising approach for improving clinical responses in B-cell lymphoma and
      multiple myeloma. Therapeutic modalities that generate reactive oxygen species
      (i.e., radiation, photodynamic therapy, and specific chemotherapeutic drugs) have
      been shown to be selectively cytotoxic to malignant B-cells. In this review, we
      will discuss agents that induce apoptosis in B-cell tumors by oxidative stress.
      Subsequently, a novel biochemical rationale (based on fundamental differences in
      cancer vs. normal cell oxidative metabolism) for combining oxidative stressors
      with radiotherapy and chemotherapy, that may lead to designing of more effective
      treatment strategies for B-cell malignancies, will be discussed. Besides
      providing potential curative benefit, such novel therapies could also selectively
      target and inhibit the emergence of drug-resistance in tumor cells, which is a
      major determinant of treatment failure in many B-cell malignancies.

PMID- 21956714
TI  - Mammalian target of rapamycin regulates isoliquiritigenin-induced autophagic and
      apoptotic cell death in adenoid cystic carcinoma cells.
AB  - Previous studies, including those from our laboratory, have demonstrated that
      isoliquiritigenin (ISL), a flavonoid isolated from licorice, is a promising
      cancer chemotherapeutic agent. However the mechanisms underlying its anticancer
      effects are still far from clear. We now show, for the first time, that ISL
      triggers the mammalian target of rapamycin (mTOR)-dependent autophagic and
      apoptotic cell death in adenoid cystic carcinoma (ACC). Exposure of both ACC-2
      and ACC-M cells to ISL resulted in several specific features for autophagy,
      including the appearance of membranous vacuoles, formation of acidic vesicular
      organelles, punctate pattern of LC3 immunostaining, and an increase in autophagic
      flux. Moreover, ISL treatment also resulted in significantly increased apoptosis
      in ACC cells. The ISL-mediated autophagic and apoptotic cell death were obviously
      attenuated by transfection with dominant negative Atg5 (DN-Atg5(K130R)) plasmids
      or treatment with 3-methyladenine(3-MA). In additon, the data also revealed that
      the autophagic and apoptotic cell death induced by ISL occurred through a mTOR
      dependent pathway. More importantly, the xenograft model using ACC-M cells
      provided further evidence of the occurrence of ISL-induced autophagy and
      apoptosis in vivo, correlating with the suppresson of mTOR activation as well as
      up-regulation of Atg5 expression. Taken together, these findings in our study
      suggest that induction of mTOR-dependent autophagic and apoptotic cell death may
      be an important mechanism in cancer chemotherapy by ISL.

PMID- 21956715
TI  - So what? Does the test lead to improved health outcomes?

PMID- 21956716
TI  - Different clinical and neuropathologic phenotypes of familial ALS with A315E
      TARDBP mutation.
AB  - OBJECTIVE: To present the relationship between TARDBP gene mutation and
      clinicopathologic findings of a Japanese pedigree affected by familial
      amyotrophic lateral sclerosis (FALS). METHODS: The clinical, genetic, and
      neuropathologic characteristics of 4 members of a Japanese pedigree affected by
      FALS were examined. RESULTS: All the patients showed motor neuron signs, and 2 of
      them also had parkinsonism. We identified A315E TARDBP mutation in one patient
      per clinical disease type and found loss of anterior horn cells, Bunina bodies,
      and phosphorylated TDP-43-positive neuronal and glial cytoplasmic inclusions in
      both the patients. However, the patient with only motor neuron signs had
      degeneration of the posterior column and spinocerebellar tracts as well as
      neuronal loss of the Clarke column, and the patient with both motor neuron signs
      and parkinsonism had severe nigral degeneration without Lewy pathology.
      CONCLUSION: The clinical and neuropathologic phenotypes of FALS may differ even
      with the same mutation of TARDBP, encoding TDP-43. Isolated TDP-43 pathology can
      produce ALS-plus syndrome.

PMID- 21956717
TI  - Recovery after severe refractory status epilepticus and 4 months of coma.

PMID- 21956718
TI  - Conjoint pathologic cascades mediated by ALS/FTLD-U linked RNA-binding proteins
      TDP-43 and FUS.
AB  - The RNA-binding proteins TAR DNA-binding protein (TDP-43) and fused in sarcoma
      (FUS) play central roles in neurodegeneration associated with familial
      amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with
      ubiquitin-positive inclusions (FTLD-U). Normally localized in the nucleus, in
      sites affected by ALS and FTLD-U they are mislocalized to the cytoplasm and form
      cytoplasmic inclusions. TDP-43 and FUS are transported to the nucleus in a Ran
      GTPase-dependent manner via nuclear import receptors, but they also contribute to
      the formation of stress granules (SGs), which are intracytoplasmic structures
      incorporating RNA. C-terminal truncations of TDP-43 eliminate the nuclear
      transport signal and cause mislocalization of the protein to the cytoplasm, where
      it accumulates and forms SGs. ALS-associated FUS mutations impair nuclear
      transport and cause mislocalization of FUS to the cytoplasm, where it also
      contributes to assembly of SGs. Furthermore, the ALS susceptibility factor ataxin
      2, recently identified as a potent modifier of TDP-43 toxicity, is also a
      predicted cytoplasmic RNA-binding protein and a constituent protein of SGs,
      suggesting that it is a part of the common pathologic cascade formed by TDP-43
      and FUS. Thus, we propose that excessive mislocalization of the RNA-binding
      proteins TDP-43, FUS, and ataxin-2 into the cytoplasm leads to impairment of the
      RNA quality control system, forming the core of the ALS/FTLD-U degenerative
      cascade. In this review, we discuss the molecular basis of the novel disease
      spectrum of ALS/FTLD-U, including the neurodegenerative mechanism of the
      cytoplasmic RNA-binding proteins TDP-43 and FUS and the possibility of a novel
      therapeutic strategy.

PMID- 21956719
TI  - The (pre)hypertension limbo: is it time to lower the treatment bar?

PMID- 21956720
TI  - Evidence report: Genetic and metabolic testing on children with global
      developmental delay: report of the Quality Standards Subcommittee of the American
      Academy of Neurology and the Practice Committee of the Child Neurology Society.
AB  - OBJECTIVE: To systematically review the evidence concerning the diagnostic yield
      of genetic and metabolic evaluation of children with global developmental delay
      or intellectual disability (GDD/ID). METHODS: Relevant literature was reviewed,
      abstracted, and classified according to the 4-tiered American Academy of
      Neurology classification of evidence scheme. RESULTS AND CONCLUSIONS: In patients
      with GDD/ID, microarray testing is diagnostic on average in 7.8% (Class III), G
      banded karyotyping is abnormal in at least 4% (Class II and III), and
      subtelomeric fluorescence in situ hybridization is positive in 3.5% (Class I, II,
      and III). Testing for X-linked ID genes has a yield of up to 42% in males with an
      appropriate family history (Class III). FMR1 testing shows full expansion in at
      least 2% of patients with mild to moderate GDD/ID (Class II and III), and MeCP2
      testing is diagnostic in 1.5% of females with moderate to severe GDD/ID (Class
      III). Tests for metabolic disorders have a yield of up to 5%, and tests for
      congenital disorders of glycosylation and cerebral creatine disorders have yields
      of up to 2.8% (Class III). Several genetic and metabolic screening tests have
      been shown to have a better than 1% diagnostic yield in selected populations of
      children with GDD/ID. These values should be among the many factors considered in
      planning the laboratory evaluation of such children.

PMID- 21956721
TI  - OnabotulinumtoxinA improves quality of life and reduces impact of chronic
      migraine.
AB  - OBJECTIVE: To assess the effects of treatment with onabotulinumtoxinA (Botox,
      Allergan, Inc., Irvine, CA) on health-related quality of life (HRQoL) and
      headache impact in adults with chronic migraine (CM). METHODS: The Phase III
      Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program
      (PREEMPT 1 and 2) included a 24-week, double-blind phase (2 12-week cycles)
      followed by a 32-week, open-label phase (3 cycles). Thirty-one injections of 5U
      each (155 U of onabotulinumtoxinA or placebo) were administered to fixed sites.
      An additional 40 U could be administered "following the pain." Prespecified
      analysis of headache impact (Headache Impact Test [HIT]-6) and HRQoL (Migraine
      Specific Quality of Life Questionnaire v2.1 [MSQ]) assessments were performed.
      Because the studies were similar in design and did not notably differ in outcome,
      pooled results are presented here. RESULTS: A total of 1,384 subjects were
      included in the pooled analyses (onabotulinumtoxinA, n = 688; placebo, n = 696).
      Baseline mean total HIT-6 and MSQ v2.1 scores were comparable between groups;
      93.1% were severely impacted based on HIT-6 scores >=60. At 24 weeks, in
      comparison with placebo, onabotulinumtoxinA treatment significantly reduced HIT-6
      scores and the proportion of patients with HIT-6 scores in the severe range at
      all timepoints including week 24 (p < 0.001). OnabotulinumtoxinA treatment
      significantly improved all domains of the MSQ v2.1 at 24 weeks (p < 0.001).
      CONCLUSIONS: Treatment of CM with onabotulinumtoxinA is associated with
      significant and clinically meaningful reductions in headache impact and
      improvements in HRQoL. CLASSIFICATION OF EVIDENCE: This study provides Class 1A
      evidence that onabotulinumtoxinA treatment reduces headache impact and improves
      HRQoL.

PMID- 21956722
TI  - Presence of baseline prehypertension and risk of incident stroke: a meta
      analysis.
AB  - OBJECTIVE: To qualitatively and quantitatively assess the association of
      prehypertension with incident stroke through a meta-analysis of prospective
      cohort studies. METHODS: We searched Medline, Embase, the Cochrane Library, and
      bibliographies of retrieved articles. Prospective cohort studies were included if
      they reported multivariate-adjusted relative risks (RRs) and corresponding
      95%confidence intervals (CI) of stroke with respect to baseline prehypertension.
      RESULTS: Twelve studies with 518,520 participants were included. Prehypertension
      was associated with risk of stroke (RR 1.55, 95% CI 1.35-1.79; p < 0.001). Seven
      studies further distinguished a low prehypertensive population (systolic blood
      pressure [SBP] 120-129 mm Hg or diastolic blood pressure [DBP] 80-84 mm Hg) and a
      high prehypertensive population (SBP 130-139 mm Hg or DBP 85-89 mm Hg). Among
      persons with lower-range prehypertension, stroke risk was not significantly
      increased (RR 1.22, 0.95-1.57). However, for persons with higher values within
      the prehypertensive range, stroke risk was substantially increased (RR 1.79, 95%
      CI 1.49-2.16). CONCLUSIONS: Prehypertension is associated with a higher risk of
      incident stroke. This risk is largely driven by higher values within the
      prehypertensive range and is especially relevant in nonelderly persons.
      Randomized trials to evaluate the efficacy of blood pressure reduction in persons
      with this designation are warranted.

PMID- 21956724
TI  - TDP-43 and FUS in ALS/FTLD: will common pathways fit all?

PMID- 21956723
TI  - ALS clinical trials: do enrolled patients accurately represent the ALS
      population?
AB  - OBJECTIVE: To assess the effect of eligibility criteria in amyotrophic lateral
      sclerosis (ALS) clinical trials on the representativeness of the enrolled
      population. METHODS: Patients enrolled in 8 placebo-controlled clinical trials in
      our ALS center from 2003 to 2008 were compared 1) to the patients included a
      prospective epidemiologic register (Piemonte and Valle d'Aosta register for ALS,
      PARALS) in the same period and 2) the subset of PARALS patients who met the usual
      criteria for inclusion in clinical trials (PARALS-ct) (definite, probable,
      probable laboratory-supported ALS; age between 18 and 75 years; disease duration
      <36 months; vital capacity at diagnosis >=70%; score >=3 at the items swallowing
      and respiratory insufficiency at the Amyotrophic Lateral Sclerosis Functional
      Rating Scale-revised scale; riluzole therapy). RESULTS: A total of 164 patients
      were enrolled in 8 different clinical trials. The PARALS cohort included 813
      patients, of whom 539 (66.3%) met the entry criteria for clinical trials.
      Patients enrolled in clinical trials were different from both epidemiologic
      cohorts, since they were younger, had a longer diagnostic delay, and were more
      likely to have a spinal onset, and to be men. Tracheostomy-free survival was
      significantly longer in the group of patients enrolled in clinical trials (median
      survival time, trial patients, 3.9 years [95% confidence interval (CI) 3.4-4.4];
      PARALS, 2.6 [2.4-2.8]; PARALS-ct, 2.9 [2.7-3.1]). CONCLUSIONS: Patients enrolled
      in clinical trials do not satisfactorily represent the ALS population;
      consequently, the findings of ALS trials lack of external validity
      (generalizability). Efforts should be made to improve patients' recruitment in
      trials, particularly enrolling incident rather than prevalent cases.

PMID- 21956726
TI  - Dysprosody during epileptic seizures lateralizes to the nondominant hemisphere.
AB  - OBJECTIVE: In human speech, the changes in intonation, rhythm, or stress reflect
      emotions or intentions and are called prosody. Dysprosody is the impairment of
      prosody and has been described in stroke and neurodegenerative disorders. Reports
      in epilepsy patients are limited to case reports. METHODS: We assessed prosody
      qualitatively and quantitatively in 967 focal epilepsy patients. The qualitative
      assessment was performed by 2 native German speakers, and the quantitative
      frequency analysis used linguistic software tools. For the quantitative analysis,
      the formant F0 (a frequency peak, which is an approximation of pitch) and the
      further spectral frequency peaks of our patients' voices were analyzed. RESULTS:
      We found 26 patients with ictal dysprosody through qualitative analysis (2.7% of
      all focal epilepsies). The qualitative changes affected mostly the pitch and the
      loss of melody. The seizure patterns at the time of ictal dysprosody were always
      in the nondominant hemisphere (100%) and were mostly right temporal (n = 22;
      84.6%). Quantitative analysis of 15 audio samples (11 patients) showed a change
      in the frequency of formant F0 of several patients and a reduction of frequency
      variation during ictal speech, expressed as the SD of formant F0 (ictal 14.1 vs
      interictal 27.2). CONCLUSIONS: Ictal dysprosody localizes seizure onset or
      propagation to the nondominant temporal lobe. This information can be used in the
      evaluation of patients considered for resective epilepsy surgery.

PMID- 21956725
TI  - Randomized, phase III study results of clobazam in Lennox-Gastaut syndrome.
AB  - OBJECTIVE: To evaluate efficacy and safety of clobazam, a 1,5-benzodiazepine, as
      adjunctive therapy for Lennox-Gastaut syndrome (LGS). METHODS: Patients aged 2-60
      years were randomized to placebo or clobazam 0.25, 0.5, or 1.0 mg/kg/day. Study
      consisted of 4-week baseline, 3-week titration, and 12-week maintenance phases,
      followed by a 2- or 3-week taper or continuation in an open-label extension.
      Primary endpoint was percentage decrease in mean weekly drop seizure rates during
      maintenance vs baseline phases for modified intention-to-treat (mITT) population.
      Secondary outcomes included other seizure types, responder rates, and physicians'
      and caregivers' global assessments. RESULTS: A total of 305 patients were
      screened, 238 were randomized, and 217 composed the mITT population. Of patients
      enrolled after a protocol amendment, 125/157 (79.6%) completed. Average weekly
      drop seizure rates decreased 12.1% for placebo vs 41.2% (p = 0.0120), 49.4% (p =
      0.0015), and 68.3% (p < 0.0001) for the clobazam 0.25-, 0.5-, and 1.0-mg/kg/day
      groups. Responder rates (>=50%) were 31.6% (placebo) vs 43.4% (p = 0.3383), 58.6%
      (p = 0.0159), and 77.6% (p < 0.0001) for clobazam 0.25-, 0.5-, and 1.0-mg/kg/day
      groups. Physicians' and caregivers' assessments indicated clobazam significantly
      improved symptoms. Somnolence, pyrexia, upper respiratory infections, and
      lethargy were the most frequent adverse events reported for clobazam.
      CONCLUSIONS: Clobazam significantly decreased weekly drop seizure rates in LGS.
      No new safety signals were identified. CLASSIFICATION OF EVIDENCE: This study
      provides Class II evidence that clobazam as adjunctive therapy is efficacious, in
      a dosage-dependent manner, in reducing mean weekly drop seizure rates of patients
      with LGS over 12 weeks.

PMID- 21956727
TI  - Cerebral microbleeds and cognitive functioning in the PROSPER study.
AB  - OBJECTIVES: Cerebral microbleeds (MBs) are an important indicator of cerebral
      small-vessel disease, and their prevalence increases with increasing age. Little
      is known about the functional consequences of MBs in the aging population. In
      this study we investigated whether the presence and location of MBs are
      associated with cognition in the PROSPER study. METHODS: For 439 subjects the
      number and location (cortico-subcortical, deep white matter, basal ganglia, and
      infratentorial) of the MBs was recorded. Difference in cognitive performance
      between subjects with and without MBs was calculated by entering the variables
      sex, age, white matter hyperintensity volume, infarction, and MBs in a linear
      mixed model. Differences in cognition between subjects with and without one or
      more MBs at different anatomic locations were assessed using the same model.
      RESULTS: We found that after correction for sex, age, white matter hyperintensity
      volume, and infarction, subjects with infratentorial MBs had a significantly
      lower score on the Immediate Picture-Word Learning test, Delayed Picture-Word
      Learning, and Instrumental Activities of Daily Living. CONCLUSIONS: Our data
      demonstrate that in elderly individuals at increased vascular risk,
      infratentorial MBs are associated with loss in cognitive functioning.

PMID- 21956728
TI  - Physical exercise improves cardiac autonomic modulation in hypertensive patients
      independently of angiotensin-converting enzyme inhibitor treatment.
AB  - We investigated the influence of angiotensin-converting enzyme inhibitor (ACEi)
      treatment and physical exercise on arterial pressure (AP) and heart rate
      variability (HRV) in volunteer patients with hypertension. A total of 54
      sedentary volunteers were divided into three groups: normotensive (NT Group),
      hypertensive (HT Group) and HT volunteers treated with ACEi (ACEi Group). All
      volunteers underwent an aerobic physical-training protocol for 15 weeks. HRV was
      investigated using a spectral analysis of a time series of R-R interval (RRi)
      that was obtained in a supine position and during a tilt test. Physical training
      promoted a significant reduction in the mean arterial pressure of the HT group
      (113+/-3 vs. 106+/-1 mm Hg) and the ACEi group (104+/-2 vs. 98+/-2 mm Hg).
      Spectral analysis of RRi in the supine position before physical training
      demonstrated that the NT and ACEi groups had similar values at low frequency (LF;
      0.04-0.15 Hz) and high frequency (HF; 0.15-0.5 Hz) oscillations. The HT group had
      an increase in LF oscillations in absolute and normalized units and a decrease in
      HF oscillations in normalized units compared with the other groups. The HT group
      had the lowest responses to the tilt test during LF oscillations in normalized
      units. Physical training improved the autonomic modulation of the heart rate in
      the supine position only in the HT group. Physical training promoted a similar
      increase in autonomic modulation responses in the tilt test in all groups. Our
      findings show that aerobic physical training improves cardiac autonomic
      modulation in HT volunteers independently of ACEi treatment.

PMID- 21956729
TI  - N-sulfinylcarboximidates as a new class of chiral bidentate ligands: application
      to asymmetric coordination chemistry.

PMID- 21956730
TI  - Natural variations at position 93 of the invariant Valpha24-Jalpha18 alpha chain
      of human iNKT-cell TCRs strongly impact on CD1d binding.
AB  - Human invariant natural killer T (NKT) cell TCRs bind to CD1d via an "invariant"
      Valpha24-Jalpha18 chain (iNKTalpha) paired to semi-invariant Vbeta11 chains
      (iNKTbeta). Single-amino acid variations at position 93 (p93) of iNKTalpha,
      immediately upstream of the "invariant" CDR3alpha region, have been reported in a
      substantial proportion of human iNKT-cell clones (4-30%). Although p93, a serine
      in most human iNKT-cell TCRs, makes no contact with CD1d, it could affect CD1d
      binding by altering the conformation of the crucial CDR3alpha loop. By generating
      recombinant refolded iNKT-cell TCRs, we show that natural single-nucleotide
      variations in iNKTalpha, translating to serine, threonine, asparagine or
      isoleucine at p93, exert a powerful effect on CD1d binding, with up to 28-fold
      differences in affinity between these variants. This effect was observed with
      CD1d loaded with either the artificial alpha-galactosylceramide antigens KRN7000
      or OCH, or the endogenous glycolipid beta-galactosylceramide, and its importance
      for autoreactive recognition of endogenous lipids was demonstrated by the binding
      of variant iNKT-cell TCR tetramers to cell surface expressed CD1d. The serine
      containing variant showed the strongest CD1d binding, offering an explanation for
      its predominance in vivo. Complementary molecular dynamics modeling studies were
      consistent with an impact of p93 on the conformation of the CDR3alpha loop.

PMID- 21956733
TI  - [Goals and activities of the "Austrian Society of Internal Medicine Angiology -
      OGIA"].

PMID- 21956731
TI  - Versatile stereoselective cycloadditions between heterocumulenes and
      phosphagermaallene Tip(tBu)Ge=C=PMes*: experimental and theoretical
      investigations.
AB  - Phosphagermaallene Tip(tBu)Ge=C=PMes* 1 (Tip=2,4,6-triisopropylphenyl, Mes*=2,4,6
      tri-tert-butylphenyl) reacts with phenyl isocyanate and tert-butyl isocyanate by
      a [2+2] cycloaddition that involves the Ge=C and C=O double bonds to afford 1-oxa
      2-germacyclobutanes 2 and 3. With N,N'-dicyclohexylcarbodiimide, a [2+2]
      cycloaddition is observed between the Ge=C and C=N unsaturations to lead to 1-aza
      2-germacyclobutane 6 with exocyclic P=C and C=N double bonds. In sharp contrast,
      1 reacts with phenyl isothiocyanate, ethyl isothiocyanate, and carbon disulfide
      according to a [3+2] cycloaddition that involves the whole Ge=C=P unit and the
      C=S double bond to give transient phosphagermacarbenes (PGeHCs) 11, 12, and 13.
      These new PGeHCs undergo C-H insertions into one o-tBu group of Mes* (in the case
      of 11 and 12) or one o-iPr group of Tip (in the case of 13) with formation of
      tricyclic compounds 8, 9, and 10, respectively. The reaction mechanisms that
      involve 1 and the phenyl isocyanate and the phenyl isothiocyanate are described
      and their regioselectivity is explained by theoretical calculations.

PMID- 21956738
TI  - Representation of protein 3D structures in spherical (rho, phi, theta)
      coordinates and two of its potential applications.
AB  - Three-dimensional objects can be represented using cartesian, spherical or
      cylindrical coordinate systems, among many others. Currently all protein 3D
      structures in the PDB are in cartesian coordinates. We wanted to explore the
      possibility that protein 3D structures, especially the globular type
      (spheroproteins), when represented in spherical coordinates might find useful
      novel applications. A Fortran program was written to transform protein 3D
      structure files in cartesian coordinates (x,y,z) to spherical coordinates (rho,
      phi, theta), with the centroid of the protein molecule as origin. We present here
      two applications, namely, (1) separation of the protein outer layer (OL) from the
      inner core (IC); and (2) identifying protrusions and invaginations on the protein
      surface. In the first application, phi and theta were partitioned into suitable
      intervals and the point with maximum rho in each such 'phi-theta bin' was
      determined. A suitable cutoff value for rho is adopted, and for each phi-theta
      bin, all points with rho values less than the cutoff are considered part of the
      IC, and those with rho values equal to or greater than the cutoff are considered
      part of the OL. We show that this separation procedure is successful as it gives
      rise to an OL that is significantly more enriched in hydrophilic amino acid
      residues, and an IC that is significantly more enriched in hydrophobic amino acid
      residues, as expected. In the second application, the point with maximum rho in
      each phi-theta bin are sequestered and their frequency distribution constructed
      (i.e., maximum rho's sorted from lowest to highest, collected into 1.50A
      intervals, and the frequency in each interval plotted). We show in such plots
      that invaginations on the protein surface give rise to subpeaks or shoulders on
      the lagging side of the main peak, while protrusions give rise to similar
      subpeaks or shoulders, but on the leading side of the main peak. We used the
      dataset of Laskowski et al. (1996) to demonstrate both applications.

PMID- 21956739
TI  - Homology modeling and function prediction of hABH1, involving in repair of
      alkylation damaged DNA.
AB  - Inhibition of DNA repair mechanism through alkylating agents in tumor cells is an
      important method for cancer treatment. Alkylation damage repair gene AlkB was
      first reported in E. coli. In human and other mammals eight distinguishing
      homologs of AlkB were detected and are known as hABH1 to hABH8. Crystal
      structures of hABH2 and hABH3 elucidated the role of human AlkB homologs involved
      in DNA and RNA repair pathways. No crystal structure of hABH1 is available for
      the detailed study on the nature and function of the molecule. In the present
      work we performed homology modeling and different tertiary structure based study
      on human AlkB homolog hABH1. hABH1.B99990005.pdb, out of five models generated
      using the program modeler 9v7 and validated with Ramachandran plot showed that
      97.9% residues were in the favored and additional allowed region and less
      residues in disallowed region, which is the best among all models. Functions of
      the selected model were studied in terms of cation binding, transition metal ion
      binding and metal ion binding function with oxidoreductase activity. Two
      functional sites and one conserved cluster were detected in the protein. Ligand
      binding residue prediction showed four ligand clusters with 17 ligands in cluster
      1. In this cluster seven Fe(2+) heterogen counts were detected. Most
      significantly, predicted iron-binding motif in hABH1 was found as His231-X-Asp233
      XnHis287 which corresponds to His131-XAsp133-Xn-His187 in AlkB of E. coli
      homologue. This shows the similar pattern of aspartic acid and histidine residues
      in the functional part of the protein both in human and E. coli. These results
      can be used further to design inhibitors aiding chemotherapy and cancer related
      diseases.

PMID- 21956740
TI  - Identifying therapeutic template by evaluating the structural stability of gram
      positive anti-bacterial peptides--a computational approach.
AB  - Clinically significant antibiotic resistance has evolved against virtually every
      antibiotic deployed. Yet the development of new classes of antibiotics has lagged
      far behind our growing need for such drugs. Antimicrobial peptides (AMPs) have
      emerged as novel therapeutics hailed for their bactericidal and immunomodulatory
      properties. However, the process of optimizing antimicrobial peptide stability,
      using large peptide libraries is both tedious and expensive. The intent of this
      study is to analyze computationally the stability of anti-bacterial peptides
      (ABPs), particularly gram positive and to discover a potential template from a
      pool of ABPs for therapeutic use. Consequently we highlighted that MiAMP1 appears
      advantageous over the other ABPs with respect to stability, and may provide a
      convenient platform for the development of anti-bacterial therapeutic peptide.

PMID- 21956741
TI  - Molecular docking studies of curcumin analogs with phospholipase A2.
AB  - The enzyme phospholipase A2 is responsible for the hydrolysis of membrane
      phospholipids that release arachidonic acid, which serves as a substrate for pro
      inflammatory mediators, such as prostaglandins and leucotriens. The binding of
      the substrate to PLA2 occurs through a well-formed hydrophobic channel. So
      blocking the hydrophobic channel is an effective way to inhibit PLA2. Compounds
      inhibiting PLA2 have been implicated as potential therapeutic agents in the
      treatment of inflammation related diseases. Curcumin is a well studied compound
      isolated from the plant Curcuma longa. The PLA2 inhibiting activity of curcumin
      has been studied in our laboratory. The present study focuses whether any of the
      curcumin analogs can bind PLA2 more strongly than curcumin. To check this,
      binding of twenty eight different curcumin analogs to PLA2 have been studied by
      molecular modeling and docking. The mode of interactions of compounds with strong
      binding are discussed and reported here. It has been observed that four analogs
      namely rosmarinic acid, tetrahydrocurcumin, dihydrocurucmin and hexahydrocurcumin
      possess better binding energy than curcumin. The present study may lead to the
      better understanding of PLA2 inhibition by curcumin analogs. This may help to
      develop better anti-inflammatory drugs.

PMID- 21956742
TI  - Interaction of 5-(2, 4-dimethylbenzyl) pyrrolidin-2-one with selected antifungal
      drug target enzymes by in silico molecular docking studies.
AB  - Currently the criteria used for selecting optimal new antifungal drug candidates
      include inhibitors of fungal cell wall biosynthesis, essential reaction and
      pathways. In silico approach resulting in the identification of essential
      reactions and pathways spreads across several parts of metabolism. The aim of the
      present study was to study the interaction of the isolated anti-Aspergillus
      compound, 5-(2, 4-dimethylbenzyl) pyrrolidin-2-one (DMBPO) from a novel
      Streptomyces VITSVK5 spp. with 6 selected antifungal drug target enzymes by in
      silico molecular docking approach. The compound DMBPO showed minimum binding
      energy (-6.66 kcal/mol) with 14 alpha-sterol demethylase (cyp51), (-5.65
      kcal/mol) with Rubythrine, and (-4.43 kcal/mol) with beta-1-3 Glucan binding
      protein. Two enzymes 14 alpha-sterol demethylase (cyp51) and beta-1-3 Glucan were
      reported to be mostly responsible for drug resistance in Aspergillus species. The
      compound DMBPO interacted with several amino acid residues, of which leucine was
      found to be common among all the target enzymes for protein and hydrogen bond
      formation. Our results suggest that DMBPO could target Aspergillus fungal
      proteins to exhibit anti-Aspergillus activity in drug resistant strains.

PMID- 21956743
TI  - Comprehensive structural and functional characterization of Mycobacterium
      tuberculosis UDP-NAG enolpyruvyl transferase (Mtb-MurA) and prediction of its
      accurate binding affinities with inhibitors.
AB  - Tuberculosis (TB) remains the most frequent and important infectious disease
      causing morbidity and death in the world. One third of the world's population is
      infected with Mycobacterium tuberculosis (Mtb), the etiologic agent of TB. The
      bacterial enzyme MurA catalyzes the transfer of enolpyruvate from
      phosphoenolpyruvate (PEP) to uridine diphospho-N-acetylglucosamine (UNAG), which
      is the first committed step of bacterial cell wall biosynthesis. In this work, 3D
      structure model of Mtb-MurA enzyme has been developed for the first time by
      homology modeling and molecular dynamics simulation techniques. Multiple sequence
      alignment and 3D structure model provided the putative substrate binding pocket
      of Mtb-MurA with respect to E. coli MurA. This analysis was helpful in
      identifying the binding sites and molecular function of the MurA homologue.
      Molecular docking study was performed on this 3D structure model, using different
      classes of inhibitors like fosfomycin, cyclic disulfide analog RWJ-3981,
      pyrazolopyrimidine analog RWJ-110192, purine analog RWJ-140998, 5-sulfonoxy
      anthranilic acid derivatives T6361, T6362 and the results showed that the 5
      sulfonoxyanthranilic acid derivatives showed the best interaction compared to
      other inhibitors. We also designed new efficient analogs of T6361 and T6362 which
      showed even better interaction with Mtb-MurA than the parental 5-sulfonoxy
      anthranilic acid derivatives. Further the comparative molecular electrostatic
      potential and cavity depth analysis of Mtb-MurA suggested several important
      differences in its substrate and inhibitor binding pocket. Such differences could
      be exploited in the future for designing a more specific inhibitor for Mtb-MurA
      enzyme.

PMID- 21956744
TI  - Screening natural products database for identification of potential
      antileishmanial chemotherapeutic agents.
AB  - Leishmaniasis is a parasitic infection caused by unicellular protozoan organism
      belonging to the family Trypanosomatidae. Among various forms of the disease,
      visceral leishmaniasis is the most lethal and caused by Leishmania infantum or
      Leishmania donovani. The redox metabolism of parasite requires a key enzyme,
      trypanothione reductase which is a validated drug target. In the past decade, it
      was observed that these protozoan parasites had developed resistance against many
      of available drugs. Importantly in the case of visceral leishmaniasis drug
      resistance is very high in the Indian subcontinent, a major endemic region of
      Leishmania donovani infection. In search for new drugs, we aim to identify
      potential natural product inhibitors of trypanothione reductase which can be
      further developed as anti-leishmanial drug. We have performed in silico virtual
      screening of a natural product data set of 800 diverse chemical entities.
      Leishmania infantum trypanothione reductase crystal structure (PDB ID: 2JK6) was
      used in the virtual screening process, docking studies to identify potential lead
      compounds. The compounds were sorted based upon their binding energy and the top
      50 ranked protein-inhibitor complexes were clustered using AuPosSOM to ligand
      foot print the interactions. We report a few alkaloids and sterols for the first
      time, which could be potential trypanothione reductase inhibitors. The
      footprinting of protein-inhibitor interactions into clusters has also provided
      clues on various possible orientations that inhibitors can attain at the active
      site of Trypanothione reductase. Moreover, biological significance of the
      interactions has also been discussed.

PMID- 21956745
TI  - A comparative study of support vector machine, artificial neural network and
      bayesian classifier for mutagenicity prediction.
AB  - Mutagenicity is the capability of a chemical to carry out mutations in genetic
      material of an organism. In order to curtail expensive drug failures due to
      mutagenicity found in late development or even in clinical trials, it is crucial
      to determine potential mutagenicity problems as early as possible. In this work
      we have proposed three different classifiers, i.e. Support Vector Machine (SVM),
      Artificial Neural Network (ANN) and bayesian classifiers, for the prediction of
      mutagenicity of compounds based on seventeen descriptors. Among the three
      classifiers Radial Basis Function (RBF) kernel based SVM classifier appeared to
      be more accurate for classifying the compounds under study on mutagens and non
      mutagens. The overall prediction accuracy of SVM model was found to be 71.73%
      which was appreciably higher than the accuracy of ANN based classifier (59.72%)
      and bayesian classifier (66.61%). It suggests that SVM based prediction model can
      be used for predicting mutagenicity more accurately compared to ANN and bayesian
      classifier for data under consideration.

PMID- 21956746
TI  - Hepatitis C virus-specific cellular and humoral immune responses following
      immunization with a multi-epitope fusion protein.
AB  - Hepatitis C virus (HCV) is an important causative agent of acute and chronic
      hepatitis worldwide. We prepared a fusion protein in the vector of pET-11d that
      included three conserved broadly neutralizing B-cell epitopes and a series of T
      cell epitopes located in the HCV NS3 region. In vivo administration of this
      fusion construct resulted in specific CD8+ cytotoxic lymphocytes in both PBMCs
      and splenocytes that could recognize specific antigen sites that could be
      detected by FACS. An HCVcc system was established and applied to detect HCV
      specific neutralizing antibodies. These results suggest that the multi-epitope
      fusion protein is immunogenic and can elicit both humoral and cellular immune
      responses. In particular, this fusion protein is able to elicit HCV-specific
      neutralizing antibodies, which are critical for viral clearance. This construct
      may be significant for vaccine development and could be a potential candidate to
      be included in the design of a prophylactic and therapeutic vaccine against HCV.

PMID- 21956747
TI  - [Conservative and surgical therapy for chemical and thermal eye burns].

PMID- 21956748
TI  - [A 69-year-old patient with brown-black pigmentation of the sclera].
AB  - In a 69-year-old man with ochronosis, circumscribed brown-black scleral spots
      with injection of conjunctival vessels and some small pigmentations of the
      peripheral superficial cornea occurred. Ochronosis is an autosomal recessive
      chronic disease, whereby early detection of cardiac valvular defects and
      arthritis is important particularly in patients who are older than 40 years.

PMID- 21956749
TI  - [Corneal opacity in a contact lens wearer on hemodialysis for renal failure].
AB  - A 53-year-old contact lens wearer on renal dialysis developed visual impairment
      due to corneal opacity. The opacity was of a crystalline type and diffusely
      scattered in the anterior cornea. As oxalosis was suspected ascorbic acid was
      immediately omitted from the dialysis treatment schedule. Within a few weeks the
      visual acuity recovered and the corneas became nearly clear. The cornea is an
      uncommon manifestation site for oxalosis. Nevertheless, one should be aware of
      this possible sign for oxalosis, which can be a life-threatening complication of
      treatment with high dose ascorbic acid.

PMID- 21956750
TI  - [Bilateral disc-like corneal opacity before cataract extraction].
AB  - An 81-year-old patient presented for cataract extraction of the right eye. In
      addition a bilateral disc-like corneal opacity was present which was classified
      as central cloudy corneal dystrophy of Francois. This rare and clinically
      unproblematic condition will be discussed.

PMID- 21956751
TI  - Reactions of ZnR2 compounds with dibenzoyl: characterisation of the alkyl
      transfer products and a striking product-inhibition effect.
AB  - The first systematic theoretical and experimental studies of reaction systems
      involving ZnR(2) (R=Me, Et or tBu) with dibenzoyl (dbz) as a non-innocent ligand
      revealed that the character of the metal-bonded R group as well as the ratio of
      the reagents and the reaction temperature significantly modulate the reaction
      outcome. DFT calculations showed four stable minima for initial complexes formed
      between ZnR(2) and dbz and the most stable structure proved to be the 2:1 adduct;
      among the 1:1 adducts three structural isomers were found of which the most
      stable complex had the monodentate coordination mode and the chelate complex with
      the s-cis conformation of the dbz unit appeared to be the least stable form.
      Interestingly, the reaction involving ZnMe(2) did not lead to any alkylation
      product, whereas the employment of ZntBu(2) resulted in full conversion of dbz to
      the O-alkylated product [tBuZn{PhC(O)C(OtBu)Ph}] already at -20  degrees C. A
      more complicated system was revealed for the reaction of dbz with ZnEt(2).
      Treatment of a solution of dbz in toluene with one equivalent of ZnEt(2) at room
      temperature afforded a mixture of the O- and C-alkylated products
      [EtZn{PhC(O)C(OEt)Ph}] and [EtZn{OC(Ph)C(O)(Et)Ph}], respectively. The formation
      of the C-alkylated product was suppressed by decreasing the initial reaction
      temperature to -20  degrees C. Moreover, in the case of the dbz/ZnEt(2) system
      monitoring of the dbz conversion over the entire reaction course revealed a
      product inhibition effect, which highlights possible participation of multiple
      equilibria of different zinc alkoxide/ZnEt(2) aggregates. Diffusion NMR studies
      indicated that dbz forms an adduct with the O-alkylated product, which is a
      competent species for executing the inhibition of the alkylation event.

PMID- 21956753
TI  - Assessing how a woman feels about her clitoris: commentary on Veale and Daniels
      (2011).

PMID- 21956752
TI  - Extrinsic and local glutamatergic inputs of the rat hippocampal CA1 area
      differentially innervate pyramidal cells and interneurons.
AB  - The two main glutamatergic pathways to the CA1 area, the Schaffer
      collateral/commissural input and the entorhinal fibers, as well as the local
      axons of CA1 pyramidal cells innervate both pyramidal cells and interneurons. To
      determine whether these inputs differ in their weights of activating GABAergic
      circuits, we have studied the relative proportion of pyramidal cells and
      interneurons among their postsynaptic targets in serial electron microscopic
      sections. Local axons of CA1 pyramidal cells, intracellularly labeled in vitro or
      in vivo, innervated a relatively high proportion of interneuronal postsynaptic
      targets (65.9 and 53.8%, in vitro and in vivo, respectively) in stratum (str.)
      oriens and alveus. In contrast, axons of in vitro labeled CA3 pyramidal cells in
      str. oriens and str. radiatum of the CA1 area made synaptic junctions
      predominantly with pyramidal cell spines (92.9%). The postsynaptic targets of
      anterogradely labeled medial entorhinal cortical boutons in CA1 str. lacunosum
      moleculare were primarily pyramidal neuron dendritic spines and shafts (90.8%).
      The alvear group of the entorhinal afferents, traversing str. oriens, str.
      pyramidale, and str. radiatum showed a higher preference for innervating
      GABAergic cells (21.3%), particularly in str. oriens/alveus. These data
      demonstrate that different glutamatergic pathways innervate CA1 GABAergic cells
      to different extents. The results suggest that the numerically smaller CA1 local
      axonal inputs together with the alvear part of the entorhinal input
      preferentially act on GABAergic interneurons in contrast to the CA3, or the
      entorhinal input in str. lacunosum-moleculare. The results highlight differences
      in the postsynaptic target selection of the feed-forward versus recurrent
      glutamatergic inputs to the CA1 and CA3 areas.

PMID- 21956754
TI  - Fluorescent and superparamagnetic hybrid quantum clusters for magnetic separation
      and imaging of cancer cells from blood.
AB  - We demonstrate here the generation of fluorescent superparamagnetic quantum
      clusters through a greener aqueous route by fusing highly fluorescent gold
      clusters with superparamagnetic nanoparticles. We conjugated transferrin onto the
      hybrid clusters to get cell accessibility and assessed their hemocompatibility
      and cytotoxicity. The ability of the clusters to selectively remove cancer cell
      lines (C6 glioma cells) from fluids including blood and the fluorescent imaging
      of the separated cells is demonstrated. The pattering of the clusters in response
      to an external magnetic field is also shown. Efficient cancer cell separation,
      imaging and magnetic pattering can be realized by the highly hemocompatible and
      noncytotoxic hybrid clusters reported here. It seems the probe has potential for
      further exploration in multimodal imaging of circulating cancer cells.

PMID- 21956756
TI  - Detection of deleted in malignant brain tumors 1 and runt-related transcription
      factor 3 gene expressions in bladder carcinoma.
AB  - Bladder cancer is the fifth most commonly diagnosed cancer in the United States,
      where the majority of tumors are transitional cell carcinoma. Deleted in
      malignant brain tumors 1 (DMBT1) gene is located at chromosome 10q25.3-q26.1.
      DMBT1 gene expression has yet to be investigated in patients with bladder cancer.
      Runt-related transcription factor 3 (RUNX3) is a candidate tumor suppressor gene
      which is localized on the chromosome 1p36. RUNX3 gene expression in bladder
      carcinogenesis is particularly unknown. We aimed to evaluate DMBT1 and RUNX3 gene
      expression profiles in bladder cancer and how their expressions could be related
      to carcinogenesis in the bladder and their correlation with clinicopathological
      parameters. Fifty-six paraffin embedded specimens of transitional cell carcinoma
      of the urinary bladder were used. Total RNA was extracted from bladder specimens
      and cDNA was synthesized. The quantification of DMBT1 and RUNX3 mRNAs were
      succeeded according to the manufacturers' instructions by using RT-PCR. DMBT1 and
      RUNX3 gene expressions were identified in 100% of bladder carcinoma samples. No
      significant association was found in these genes expression levels when compared
      to sex and age. RUNX3 gene expression was decreased non-significantly in high
      grade tumors. When DMBT1 gene expression was compared to tumor grades, a
      significant decrease was detected between grade I and III (P = 0.028). Disruption
      of expression in relation to tumor suppressors like DMBT1 and RUNX3 genes was
      associated with bladder cancer. Furthermore, detailed studies including these
      genes should be performed in protein levels and used more patient specimens in a
      large scale study.

PMID- 21956755
TI  - Differential transcript accumulation in chickpea during early phases of
      compatible interaction with a necrotrophic fungus Ascochyta rabiei.
AB  - The initial phases of the disease establishment are very crucial for the
      compatible interactions. Pathogens must overcome the responses generated by the
      host for the onset of disease invasion. The compatible interaction is
      inadequately represented in plant-pathogen interaction studies. To gain broader
      insight into the early responses elicited by chickpea blight fungus Ascochyta
      rabiei during compatible interaction; we isolated early responsive genes of
      chickpea using PCR based suppression subtractive hybridization (SSH) strategy. We
      obtained ~250 unique genes after homology search and redundancy elimination.
      Based on their potential cellular functions, these genes were broadly classified
      into eleven different categories viz. stress, signaling, gene regulation,
      cellular metabolism and genes of unknown functions. Present study revealed few
      unexpected genes which have a possible role in induced immunity and disease
      progression. We employed macroarray, northern blot, real-time PCR and cluster
      analysis to develop transcript profiles. Most of the genes analyzed were early
      induced and were transcriptionally upregulated upon 24 h post inoculation. Our
      approach has rendered the isolation of early responsive genes involved in
      signaling and regulation of metabolic changes upon fungal infection. The
      information obtained will help to dissect the molecular mechanisms during
      compatible chickpea-Ascochyta interactions.

PMID- 21956757
TI  - The ribosomal protein L19 mRNA is induced by copper exposure in the swordtail
      fish, Xiphophorus helleri.
AB  - Teleosts are useful vertebrate model species for understanding copper toxicity
      due to the dual entry route for copper intake via the gills and intestine. In
      this present study, we utilized the differential display reverse transcription
      polymerase chain reaction to isolate potential novel hepatic genes induced by
      sublethal copper exposure in the freshwater swordtail fish, Xiphophorus helleri.
      Full length cloning of a cDNA fragment induced by copper exposure to 1 MUg/ml
      during 24 h resulted in the positive identification of a hepatic ribosomal
      protein L19 (RPL19) gene. Further characterization of this gene revealed that its
      transcriptional expression was dependent on dosage and time of copper exposure.
      This study describes for the first time the involvement of RPL19 in copper
      toxicity, probably as a result of increase in ribosome synthesis rate to support
      activities such as cellular protein translation, transcriptional activation and
      mRNA stabilization during sublethal copper exposure.

PMID- 21956758
TI  - Rhombencephalitis / brainstem encephalitis.
AB  - Rhombencephalitis (RE) is a syndrome of multiple causes and multiple outcomes.
      Most authors now use the terms "rhombencephalitis" and "brainstem encephalitis"
      interchangeably even though anatomically they are slightly different. The
      etiologic categories of RE include infections, autoimmune diseases, and
      paraneoplastic syndromes (PNS). Listeria is the most common cause of infectious
      RE. Listeria RE primary occurs in healthy young adults. It usually occurs as a
      biphasic time course with a flu-like syndrome followed by brainstem dysfunction;
      75% of patients have a cerebrospinal fluid (CSF) pleocytosis, and almost 100%
      have an abnormal brain MRI scan. Positive CSF and blood cultures are the most
      specific for diagnosis. Treatment primarily is with ampicillin. Enterovirus 71 is
      probably the second most common infectious cause of RE; however, 95% of cases
      have occurred in the Asian-Pacific region and there is no specific treatment.
      Herpes simplex virus (HSV) is the third most common infectious cause of RE, and
      about 80% of cases are caused by HSV1 and 20% by HSV2. About 50% only had
      involvement of the brainstem whereas the other 50% also had supratentorial
      involvement of the temporal and frontal lobes. Mortality with acyclovir treatment
      was 22% versus those not on acyclovir 75%. Epstein-Barr virus (EBV) and human
      herpesvirus 6 (HHV6) have caused a few cases. The most common autoimmune etiology
      is Behcet disease. Over 90% of those with Behcet RE had abnormal MRI scans and
      94% had a CSF pleocytosis. Treatment is with corticosteroids and
      immunosuppressive agents, but only 25% have complete recovery. Paraneoplastic
      causes are the third category of RE. Brain MRIs are usually normal; there is
      usually a CSF pleocytosis but the protein is usually normal. Often anti-neuronal
      antibodies can be found. Prognosis is poor and treatment is only partially
      beneficial. Because Listeria and HSV are the most common treatable acute causes
      of RE, we recommend empiric therapy with ampicillin and acyclovir for all cases
      after samples have been obtained from CSF and blood for cultures and the
      polymerase chain reaction (PCR). Antibiotics can be changed based upon MRI,
      culture results, PCR results, and antibody studies.

PMID- 21956759
TI  - Self-assembly of short peptide amphiphiles: the cooperative effect of hydrophobic
      interaction and hydrogen bonding.
AB  - The interplay between hydrogen bonding, hydrophobic interaction and the molecular
      geometry of amino acid side-chains is crucial to the development of
      nanostructures of short peptide amphiphiles. An important step towards developing
      their practical use is to understand how different amino acid side-chains tune
      hydrophobic interaction and hydrogen bonding and how this process leads to the
      control of the size and shape of the nanostructures. In this study, we have
      designed and synthesized three sets of short amphiphilic peptides (I(3)K, LI(2)K
      and L(3)K; L(3)K, L(4)K and L(5)K; I(3)K, I(4)K and I(5)K) and investigated how I
      and L affected their self-assembly in aqueous solution. The results have
      demonstrated a strong tendency of I groups to promote the growth of beta-sheet
      hydrogen bonding and the subsequent formation of nanofibrillar shapes. All I(m)K
      (m = 3-5) peptides assembled into nanofibers with consistent beta-sheet
      conformation, whereas the nanofiber diameters decreased as m increased due to
      geometrical constraint in peptide chain packing. In contrast, L groups had a weak
      tendency to promote beta-sheet structuring and their hydrophobicity became
      dominant and resulted in globular micelles in L(3)K assembly. However, increase
      in the number of hydrophobic sequences to L(5)K induced beta-sheet conformation
      due to the cooperative hydrophobic effect and the consequent formation of long
      nanofibers. The assembly of L(4)K was, therefore, intermediate between L(3)K and
      L(5)K, similar to the case of LI(2)K within the set of L(3)K, LI(2)K and I(3)K,
      with a steady transition from the dominance of hydrophobic interaction to
      hydrogen bonding. Thus, changes in hydrophobic length and swapping of L and I can
      alter the size and shape of the self-assembled nanostructures from these simple
      peptide amphiphiles.

PMID- 21956760
TI  - Psychosocial well-being and supportive care needs of cancer patients living in
      urban and rural/regional areas: a systematic review.
AB  - PURPOSE: The aim of this study was to describe what is known about levels of
      morbidity and the experience and needs of people with cancer, and their informal
      caregivers, living in rural areas. METHODS: A search of online databases for
      English language papers describing or assessing the prevalence of psychosocial
      morbidity or needs in a population of rural or regional cancer patients was
      employed. The following were excluded: intervention studies, discussion of
      service delivery, effectiveness of support groups or support via
      videoconferencing, concentrated on medical outcomes or survival rates, reported
      differences in the uptake of cancer screening or concentrated on health attitudes
      or treatment decision making. RESULTS: There were 37 studies in the review,
      including 25 quantitative studies (all surveys), 11 of which included a control
      group of urban patients and 12 qualitative studies. Until recently, most studies
      had methodological shortcomings. Only two prospective studies were identified,
      most studies focused on breast cancer and few addressed psychological morbidity.
      The majority of controlled studies reported worse outcomes for rural patients,
      who appear to have higher needs in the domains of physical/daily living. This may
      reflect more limited access to resources, a more self-sufficient lifestyle and
      personal characteristics, for example, being more stoical and less likely to ask
      for help. The need to travel for treatment caused many practical, emotional and
      financial problems for patients and burdened them with additional worry
      concerning family and work commitments. Some patients reported benefits in
      sharing experiences with others also forced to stay away from home, but most
      agreed that staying at home was preferable. CONCLUSION: This review highlights
      that whilst we are beginning to get some insight into the needs of people with
      cancer in rural areas, much is still unknown. Population-based, prospective
      studies including people with heterogeneous cancers from rural and urban settings
      are needed.

PMID- 21956761
TI  - Cigarette smoke radioactivity and lung cancer risk.
AB  - INTRODUCTION: To determine the tobacco industry's policy and action with respect
      to radioactive polonium 210 ((210)Po) in cigarette smoke and to assess the long
      term risk of lung cancer caused by alpha particle deposits in the lungs of
      regular smokers. METHODS: Analysis of major tobacco industries' internal secret
      documents on cigarette radioactivity made available online by the Master
      Settlement Agreement in 1998. RESULTS: The documents show that the industry was
      well aware of the presence of a radioactive substance in tobacco as early as
      1959. Furthermore, the industry was not only cognizant of the potential
      "cancerous growth" in the lungs of regular smokers but also did quantitative
      radiobiological calculations to estimate the long-term (25 years) lung radiation
      absorption dose (rad) of ionizing alpha particles emitted from the cigarette
      smoke. Our own calculations of lung rad of alpha particles match closely the rad
      estimated by the industry. According to the Environmental Protection Agency, the
      industry's and our estimate of long-term lung rad of alpha particles causes 120
      138 lung cancer deaths per year per 1,000 regular smokers. Acid wash was
      discovered in 1980 to be highly effectively in removing (210)Po from the tobacco
      leaves; however, the industry avoided its use for concerns that acid media would
      ionize nicotine converting it into a poorly absorbable form into the brain of
      smokers thus depriving them of the much sought after instant "nicotine kick"
      sensation. CONCLUSIONS: The evidence of lung cancer risk caused by cigarette
      smoke radioactivity is compelling enough to warrant its removal.

PMID- 21956762
TI  - The relaxation effect and mechanism of action of higenamine in the rat corpus
      cavernosum.
AB  - Higenamine mediates cardiotonic, vascular relaxation and bronchodilator effects.
      The relaxation effects and the mechanism of action of higenamine on the rat
      corpus cavernosum (CC) were assessed to investigate the effect of higenamine on
      penile erection. Strips of CC and aorta were used in organ baths for isometric
      tension studies. Tension was measured with isometric force transducers, and
      muscle relaxation was expressed as the percent decrease in precontraction induced
      by phenylephrine (PE). The relaxation reactions were investigated in an
      endothelial-denuded group and groups pretreated with N(G)-nitro-L-arginine methyl
      ester (NO synthesis inhibitor), propranolol (beta-receptor blocker), indomethacin
      (COX inhibitor), glibenclamide (K(+)(ATP) channel inhibitor), 4-aminopyridine
      (membrane potential-dependent potassium channel inhibitor) and methylene blue
      (guanylyl cyclase inhibitor) for 30 min. Intracavernous pressure (ICP) was
      assessed in rats after the intravenous administration of higenamine, and changes
      in guanosine 3',5'-cyclic monophosphate and adenosine 3',5'-cyclic monophosphate
      (cAMP) concentrations were measured on the basis of the higenamine concentration.
      Also, the combined reaction of higenamine and the phosphodiesterase type-5 (PDE
      5) inhibitors was assessed. Higenamine induced relaxation of the CC and the
      aortic strips precontracted with PE in a dose-dependent manner. The CC was
      significantly more relaxed than the aortic rings in response to the same
      higenamine concentration (P<0.05). The CC relaxation reaction was suppressed by
      the beta-receptor blocker propranolol. The cAMP concentration increased gradually
      with increased higenamine concentration (P<0.05). The ICP also increased with
      increased higenamine concentration in vivo (P<0.05). In the group pretreated with
      10(-7) M higenamine, the relaxation reaction of CC induced by the PDE-5 inhibitor
      increased significantly, compared with CC exposed to the PDE-5 inhibitor but not
      pretreated with higenamine (P<0.05). In conclusion, higenamine induced relaxation
      of the rat CC in a dose-dependent manner. The effect may be mediated through beta
      adrenoceptors. The results suggest that higenamine may be valuable as a new lead
      compound for treating erectile dysfunction.

PMID- 21956763
TI  - A fine-grained analysis of eating behavior in women with bulimia nervosa.
AB  - OBJECTIVE: In the current study, we were interested in developing a typology of
      eating in patients with bulimia nervosa (BN) based on the size of the eating
      episode, whether the episode was followed by self-induced vomiting, and the
      degree of loss of control (LOC) self-reported by participants. METHOD: Twenty-one
      women with BN, purging type, were evaluated using the Nutritional Data System for
      Research, the Eating Disorders Examination, and the Matrix. RESULTS: The most
      common type of episode resembled what might be termed "normal" eating, which
      involved the consumption of <1,000 kcal with no sense of LOC and no vomiting.
      There was an increase in severity of self-assessed LOC in objectively large
      eating episodes with vomiting. Self-reported hunger prior to eating episodes did
      not seem to be predictive of subsequent behavior. Most people were engaged in
      other behaviors while eating. DISCUSSION: The results of this study suggest a
      typology that included primarily four types of eating episodes. The results also
      suggest that when LOC is assessed on a Likert-scale rather than as a dichotomous
      variable, there is considerable variability in self-assessed degree of LOC.

PMID- 21956764
TI  - Comparative study of mercury accumulation in two fish species, (Cyprinus carpio
      and Sander lucioperca) from Anzali and Gomishan wetlands in the southern coast of
      the Caspian Sea.
AB  - Anzali and Gomishan wetlands are considered as two of the most important wetlands
      in southern coast of Caspian Sea. To investigate mercury accumulation in these
      ecosystems, total mercury concentrations were measured in the muscle tissue of
      two fish species. Higher mercury concentrations were detected in C. carpio, an
      omnivorous benthic/pelagic species (Anzali wetland: 0.2 MUg g(-1) wet weight;
      Gomishan wetland: 0.2 MUg g(-1) wet weight), than in S. lucioperca, a carnivorous
      pelagic species (Anzali: 0.06 MUg g(-1) wet weight; Gomishan: 0.15 MUg g(-1) wet
      weight).

PMID- 21956765
TI  - Care needs after primary breast cancer treatment. Survivors' associated
      sociodemographic and medical characteristics.
AB  - BACKGROUND: This study examines the care needs of rehabilitating breast cancer
      survivors and determines what sociodemographic and medical characteristics are
      associated with these care needs. METHODS: A large-scale cross-sectional study (n
      = 465, response rate = 65%) was conducted among survivors who had ended primary
      treatment less than 6 months previously. Questionnaires were completed regarding
      participants' care needs, how these needs were met and the time and manner
      preferred for receiving information and support. Care needs regarding seven
      specific rehabilitation topics were assessed separately: (1) physical
      functioning, (2) psychological functioning, (3) self and body image, (4)
      sexuality, (5) relationship with partner, (6) relationship with others, and (7)
      work, return to work and social security. RESULTS: High unmet needs were reported
      across all topics. The time preferred for receiving information and support
      across most topics was the period of breast cancer treatment. The most popular
      sources of information and support were informative brochures, consultation with
      a psychologist, information sessions and an informative website. Younger age and
      lower income were associated with care needs after treatment. CONCLUSIONS: A
      valuable contribution is made to the literature on post-treatment care needs by
      comprehensively mapping unmet needs and the preferred time and source for meeting
      those needs. This study leads to greater awareness of the struggle facing breast
      cancer survivors and should guide those developing post-treatment interventions.
      As optimal tailoring to the needs of the target group is a prerequisite for
      success, preparatory needs assessment should be essential to the development of
      supportive interventions.

PMID- 21956766
TI  - Renal status in adult volunteers in central Italy: results from Family Abbott
      Renal Disease Monitoring Project (FARM) study.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a major worldwide problem. A lack of
      CKD awareness and knowledge of associated risk factors may delay diagnosis and
      treatment. The purpose of this epidemiological study was to assess the presence
      and awareness of CKD, in addition to evaluating associated clinical
      characteristics. METHODS: This cross-sectional observational study included 573
      healthy volunteers (aged 21-62 years) based in central Italy. All participants
      underwent a nephrological visit, providing data on medical history, anamnesis and
      CKD awareness. Blood and urine samples were also collected. RESULTS: Estimated
      glomerular filtration rate (eGFR) calculated by the abbreviated Modification of
      Diet in Renal Disease (MDRD) study formula revealed that 55% of participants had
      an eGFR of <90 ml/min per 1.73 m2 compared with 24.6% by the Cockcroft-Gault
      formula (C-G; p<0.0001). Approximately 45% of participants showed an awareness of
      CKD, these subjects also having a significantly lower Framingham score (p<0.046).
      Approximately half of participants (51%) had insufficient levels (<30 ng/mL) of
      serum 25-hydroxyvitamin D (25(OH)D), with a higher proportion observed in female
      (58.3%) than male participants (45.6%, p=0.0016). Levels of 25(OH)D were
      negatively correlated with eGFR, measured by either MDRD or C-G (r=-0.12,
      p=0.0039 and r=-0.09, p=0.029 respectively). Logistic regression analysis
      revealed that male sex and increased serum creatinine levels were predictors
      associated with study outcomes (clinical risk factors). CONCLUSIONS: This study
      suggests that screening for CKD in the general population by eGFR calculations
      (MDRD or C-G) is unreliable; therefore, the monitoring of serum creatinine and
      other risk factors may be more appropriate. The presence of vitamin D
      insufficiency in apparently healthy individuals warrants further investigation.

PMID- 21956767
TI  - Nicaragua revisited: evidence of lower prevalence of chronic kidney disease in a
      high-altitude, coffee-growing village.
AB  - BACKGROUND: Chronic kidney disease (CKD) is found at epidemic levels in certain
      populations of the Pacific Coast in northwestern Nicaragua especially in younger
      men. There are knowledge gaps concerning CKD's prevalence in regions at higher
      altitudes. METHODS: A cross-sectional study of adults between the ages of 20 and
      60 years in 1 coffee-growing village in Nicaragua located at 1,000 m above sea
      level (MASL) altitude was performed. Predictors included participant sex, age,
      occupation, conventional CKD risk factors and other factors associated with CKD
      suggested by previous surveys in Central America. Outcomes included serum
      creatinine (SCr) values >1.2 mg/dL for men and >0.9 mg/dL for women, estimated
      glomerular filtration rate (GFR) <60 ml/min per 1.73 m2, dipstick proteinuria
      stratified as microalbuminuria (30-300 mg/dL) and macroalbuminuria (>300 mg/dL),
      hypertension and body mass index. RESULTS: Of 324 eligible participants, 293 were
      interviewed (90.4%), and 267 of those received the physical exam (82.4% overall).
      Of the sample, 45% were men. Prevalence rate of estimated GFR <60 ml/min per 1.73
      m2 was 0 for men (0%) and 2 for women (1.4%). The prevalence of at least
      microalbuminuria was significantly higher among men compared with women (27.5%
      vs. 21.4%, respectively; p=0.02). CONCLUSIONS: The CKD prevalence in this village
      is comparable to a previously studied Nicaraguan coffee-farming region and much
      lower than previously screened portions of northwestern Nicaragua. There is
      heterogeneity in CKD prevalence across Nicaragua. At this time, screenings should
      target individuals living in previously identified, higher risk regions. More
      work is needed to understand determinants of CKD in this resource-poor nation.

PMID- 21956768
TI  - Angiopoietin-2, endothelial dysfunction and renal involvement in patients with
      systemic lupus erythematosus.
AB  - BACKGROUND: Angiopoietin-2 (ang-2) that activates endothelial cells and increases
      vascular inflammation might have significant roles in the pathogenesis of
      glomerular diseases. This study aimed at assessing the level of ang-2 as a marker
      of renal involvement in SLE patients to elucidate its correlation with disease
      activity and endothelial dysfunction. METHODS: This study included 81 subjects.
      The control group included 21 healthy subjects. The patients group included 60
      SLE patients, 24 patients without lupus nephritis (LN) and 36 patients with LN.
      Clinical examination and laboratory investigations including 24 hours urinary
      protein, estimation of serum ang-2 and creatinine and calculation of estimated
      glomerular filtration rate (eGFR). Measurement of SLE disease activity index
      (SLEDAI), flow mediated dilatation (FMD) and carotid intima media thickness
      (CIMT) were done. Renal biopsy was done for patients with LN. RESULTS: Ang2 level
      was significantly higher in subjects with FMD <=10%, than in subjects with FMD
      >10%. Ang2 level was significantly increased in SLE patients than controls, and
      it was significantly higher in patients with LN than in patients without
      nephritis. Ang2 was significantly positively correlated with SLEDAI, 24 hours
      urinary protein and histological activity index, and was negatively correlated
      with C3, eGFR and FMD. There were no significant differences between patients
      with proliferative and non proliferative LN regarding Ang2 level. CONCLUSIONS:
      Ang2 can reflect the extent of endothelial activation and may be used as a
      biomarker of both disease activity and renal involvement in SLE patients. Ang2
      level cannot distinguish between proliferative and non proliferative lesions in
      LN.

PMID- 21956769
TI  - Outcomes of rationing dialysis therapy in biopsy-proven end-stage renal disease
      in South Africa.
AB  - BACKGROUND: Due to poverty, many countries of sub-Saharan Africa suffer a severe
      burden of end-stage renal disease (ESRD), the cause of which is often
      unidentified. We sought to identify biopsy-proven causes of ESRD in Cape Town,
      South Africa, and to determine the outcome of these patients. METHODS: Records of
      biopsies reported as ESRD over a 10-year period were selected for analysis. The
      demographic, clinical and biochemical characteristics of the patients at the time
      of biopsy were documented. The decision of the committee that assesses the
      eligibility of patients for long-term renal replacement therapy (RRT) was
      documented, and if a patient was not accepted the reasons for the rejection were
      noted. RESULTS: Chronic glomerulonephritis (CGN) was the most frequent cause of
      ESRD (31.2%); human immunodeficiency virus-associated nephropathy (HIVAN)
      accounted for 12.5% of ESRD cases. Sixty-six patients (45.8%) were never reviewed
      by the assessment committee for placement in the dialysis program. Of the
      remaining 78 patients (54.2%) reviewed for RRT, only 48/78 (61.5%) were selected.
      A higher frequency of patients with HIVAN were not accepted for RRT (17.7%) than
      patients with HIVAN who were accepted (2.1%) (p=0.008). Social factors such as
      lack of housing, alcohol abuse, illicit drug abuse, lack of transportation and
      lack of family/social support accounted for 56.7% of patients not being accepted
      for RRT. CONCLUSION: There needs to be a development of programs amongst Africans
      to provide effective solutions that tackle the burden of ESRD, especially related
      to the increasing prevalence of HIVAN.

PMID- 21956770
TI  - Ferumoxytol: a new era of iron deficiency anemia treatment for patients with
      chronic kidney disease.
AB  - Ferumoxytol is a new product approved for intravenous use by the US Food and Drug
      Administration (FDA) in the treatment of iron deficiency anemia in adults with
      chronic kidney disease. This approval was based on data from 3 open-label,
      randomized, controlled clinical trials. In all of these trials, ferumoxytol was
      well tolerated, and hemoglobin levels were significantly increased compared with
      those achieved by orally administered iron. Ferumoxytol, a superparamagnetic iron
      oxide coated with a carbohydrate shell, is also used as a magnetic resonance
      imaging (MRI) agent due to its magnetic properties. In addition, it has
      demonstrated a greater T1 relaxation time than MRI gadolinium-contrast agents.
      Currently, the Ferumoxytol Compared to Iron Sucrose Trial (FIRST) has started.
      This is a multicenter randomized trial of ferumoxytol compared with iron sucrose
      for the treatment of iron deficiency anemia in adult subjects with chronic kidney
      disease, where intravenous ferumoxytol is being compared with other intravenous
      agents to evaluate the safety of ferumoxytol and assess changes in hemoglobin
      level.

PMID- 21956772
TI  - The potential value of monitoring bone turnover markers among women on
      alendronate.
AB  - Biochemical markers of bone turnover have been proposed to monitor the response
      to bisphosphonate therapy for osteoporosis, but this requires true between-person
      differences in the response to therapy. Using mixed models we analyzed three
      annual measurements of two markers (bone alkaline phosphatase [BAP] and cross
      linked N-telopeptide of type I collagen [NTX]) from the Fracture Intervention
      Trial. We compared marker variation among women allocated to alendronate with
      that among women allocated to placebo to estimate how much variation was due to
      true between-person differences in response to treatment, and how much was due to
      random within-person fluctuations unrelated to treatment. For both markers we
      found that the mean effect of treatment differed by the baseline level of the
      marker. After allowing for this and other effects, we found large true between
      person differences in response to treatment for both markers, with a coefficient
      of variation (CV) for NTX of 25.1% and for BAP of 21.2%. However, random within
      person fluctuation was even larger, with a CV for change in NTX of 42.5% and for
      change in BAP of 25.8%. Although repeated measurements have the potential to
      reduce within person variability, even triplicate baseline marker measurements
      resulted in an averaged value that was only within 31% of the true value with 95%
      certainty. In summary, although bone turnover markers appear promising for
      monitoring between-person differences in response to treatment, their use in
      clinical practice is currently limited by large random within-person variation.

PMID- 21956771
TI  - Effect of paricalcitol and GcMAF on angiogenesis and human peripheral blood
      mononuclear cell proliferation and signaling.
AB  - BACKGROUND: In addition to its role in calcium homeostasis and bone
      mineralization, vitamin D is involved in immune defence, cardiovascular function,
      inflammation and angiogenesis, and these pleiotropic effects are of interested in
      the treatment of chronic kidney disease. Here we investigated the effects of
      paricalcitol, a nonhypercalcemic vitamin D analogue, on human peripheral blood
      mononuclear cell proliferation and signaling, and on angiogenesis. These effects
      were compared with those of a known inhibitor of angiogenesis pertaining to the
      vitamin D axis, the vitamin D-binding protein-derived Gc-macrophage activating
      factor (GcMAF). METHODS: Since the effects of vitamin D receptor agonists are
      associated with polymorphisms of the gene coding for the receptor, we measured
      the effects of both compounds on mononuclear cells harvested from subjects
      harboring different BsmI polymorphisms. RESULTS: Paricalcitol inhibited
      mononuclear cell viability with the bb genotype showing the highest effect.
      GcMAF, on the contrary, stimulated cell proliferation, with the bb genotype
      showing the highest stimulatory effect. Both compounds stimulated 3'-5'-cyclic
      adenosine monophosphate formation in mononuclear cells with the highest effect on
      the bb genotype. Paricalcitol and GcMAF inhibited the angiogenesis induced by
      proinflammatory prostaglandin E1. CONCLUSIONS: Polymorphisms of the vitamin D
      receptor gene, known to be associated with the highest responses to vitamin D
      receptor agonists, are also associated with the highest responses to GcMAF. These
      results highlight the role of the vitamin D axis in chronic kidney disease, an
      axis which includes vitamin D, its receptor and vitamin D-binding protein-derived
      GcMAF.

PMID- 21956773
TI  - Cognitive and behavioural predictors of survival in Alzheimer disease: results
      from a sample of treated patients in a tertiary-referral memory clinic.
AB  - OBJECTIVE: This study examined the influence of cognitive and non-cognitive
      factors at the time of diagnosis on the survival of patients with treated
      probable Alzheimer Disease (AD). METHODS: Consecutive patients seen at a
      regional, tertiary-referral clinic completed a battery of cognitive tests and
      assessments of activities of daily living and neuropsychiatric symptoms. These
      clinic data were linked with death certificate data for all individuals and
      survival from diagnosis was calculated. Cox regression models were constructed
      using the baseline covariates. RESULTS: The sample comprised 653 patients (459
      women), mean age 77.1 years (SD 7.6, range 48-94 years), diagnosed with probable
      AD and treated with a cholinesterase inhibitor. In the survival analysis, age was
      a consistently significant predictor of survival with a gender-adjusted hazard
      ratio of 1.35 (95% CI 1.23, 1.48) for one standard deviation increase in age. Men
      were at greater risk of death than women (age-adjusted HR 1.44, 95% CI 1.19,
      1.73). In a model adjusted for all study variables, Paired-Associate Learning
      (Cambridge Automated Neuropsychological Test Assessment Battery) and the
      psychotic factor of the Neuropsychiatric Inventory were significant predictors of
      survival. CONCLUSIONS: At diagnosis, in addition to the anticipated impact of age
      and gender, the presence of psychotic symptoms and poor performance on paired
      associate learning are also indicators of poor prognosis.

PMID- 21956774
TI  - Metabolomics of the effect of AMPK activation by AICAR on human umbilical vein
      endothelial cells.
AB  - AMP-activated protein kinase (AMPK) is a metabolic master switch expressed in a
      great number of cells and tissues. AMPK is thought to modulate the cellular
      response to different stresses that increase cellular AMP concentration. The
      adenosine analog, 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR)
      is an AMPK activator used in many studies to assess the effects of AMPK
      activation on cellular metabolism and function. However, the effect of AICAR on
      cell metabolism reaches many different pathways and metabolites, some of which do
      not seem to be fully related to AMPK activation. We have now for the first time
      used NMR metabolomics on human umbilical vein endothelial cells (HUVEC) for the
      study of the global metabolic impact of AMPK activation by AICAR. In our study,
      incubation with AICAR activates AMPK and is associated with, among others, broad
      metabolic alterations in energy metabolism and phospholipid biosynthesis. Using
      NMR spectroscopy and metabolic network tools, we analyzed the connections between
      the different metabolic switches activated by AICAR. Our approach reveals a
      strong interconnection between different phospholipid precursors and oxidation by
      products. Metabolomics profiling is a useful tool for detecting major metabolic
      alterations, generating new hypotheses and provides some insight about the
      different molecular correlations in a complex system. The present study shows
      that AICAR induces metabolic effects in cell metabolism well beyond energy
      production pathways.

PMID- 21956775
TI  - Highly efficient blue organic light-emitting diodes based on 2
      (diphenylamino)fluoren-7-ylvinylarene derivatives that bear a tert-butyl group.
AB  - Blue fluorescent materials with a 2-(diphenylamino)fluoren-7-ylvinylarene
      emitting unit and tert-butyl-based blocking units were synthesized. The
      photophysical properties of these materials, including UV/Vis absorption,
      photoluminescent properties, and HOMO-LUMO energy levels, were characterized and
      rationalized with quantum-mechanical DFT calculations. The electroluminescent
      properties of these molecules were examined through the fabrication of multilayer
      devices with a structure of indium-tin oxide, 4,4'-bis{N-[4-(N,N-di-m
      tolylamino)phenyl]-N-phenylamino}biphenyl, 4'-bis[N-(1-naphthyl)-N
      phenylamino]biphenyl, and blue materials doped in 2-methyl-9,10-di(2
      naphthyl)anthracene/tris(8-quinolinolato)aluminum/LiF/Al. All devices exhibit
      highly efficient blue electroluminescence with high external quantum efficiency
      (3.20-7.72 % at 20 mA cm(-2)). A deep-blue device with Commission Internationale
      de l'Eclairage (CIE) coordinates of (0.15, 0.11) that uses 7-[2-(3',5'-di-tert
      butylbiphenyl-4-yl)vinyl]-9,9-diethyl-2-N-(3,5-di-tert-butylphenyl)-2,4
      difluorobenzenamino-9H-fluorene as a dopant in the emitting layer showed a
      luminous efficiency and external quantum efficiency of 3.95 cd A(-1) and 4.23 %
      at 20 mA cm(-2), respectively. Furthermore, a highly efficient sky-blue device
      that uses the dopant 7-{2-[2-(3,5-di-tert-butylphenyl)-9,9'-spirobifluorene-7
      yl]vinyl}-9,9-diethyl-2-N,N-diphenylamino-9H-fluorene exhibited a luminous
      efficiency and high quantum efficiency of 10.3 cd A(-1) and 7.7 % at 20 mA cm(
      2), respectively, with CIE coordinates of (0.15, 0.20).

PMID- 21956776
TI  - Atorvastatin suppresses inflammatory response induced by oxLDL through inhibition
      of ERK phosphorylation, IkappaBalpha degradation, and COX-2 expression in murine
      macrophages.
AB  - Macrophages crosstalk with oxidized low-density lipoprotein (oxLDL), play a
      critical role in the initiation, progression, and subsequently stability of
      atherosclerotic plaques. Statins, inhibitors of HMG CoA (3-hydroxy-3
      methylglutaryl coenzyme A) reductase, reduce the expression of inflammatory
      proteins in addition to their lipid-lowering action. However, the effect and
      detailed anti-inflammation mechanisms of statins in macrophages induced by oxLDL
      remain unclearly. In the present study, we investigated the effect of
      atorvastatin on inflammatory response upon oxLDL stimulation in murine
      macrophages and analyzed the underlying mechanisms. Tumor necrosis factor
      (TNF)alpha and monocyte chemoattractant protein-1 (MCP-1) mRNA levels were
      assayed by real-time PCR. The expression of cyclooxygenases-2 (COX-2) was
      detected by real-time PCR and Western blotting. While mitogen-activated protein
      kinase (MAPK) phosphorylation and IkappaBalpha degradation were determined by
      Western blotting. Our results showed that exposure of RAW264.7 cells to oxLDL,
      substantially changed the morphology of the cells and increased TNFalpha and MCP
      1 secretion. While pretreatment with atorvastatin resulted in a significant
      inhibition of oxLDL-induced morphological alteration and inflammatory cytokines
      expression in a dose-dependent fashion. Further investigation of the molecular
      mechanism revealed that oxLDL upregulated the transcription and protein
      expression of COX-2 in a time-dependent manner. Whereas, pretreatment with
      atorvastatin suppressed COX-2 expression, MAPK activation and IkappaBalpha
      degradation. Thus, we conclude that the anti-inflammatory effect of atorvastatin
      is mediated through the inhibition of proinflammatory COX-2. Furthermore,
      suppression of ERK phosphorylation and IkappaBalpha degradation is involved in
      this regulation. Our findings provide a novel evidence that statins suppress
      inflammatory response, exert its anti-atherogenic actions via against
      inflammation beyond cholesterol-lowing effect.

PMID- 21956777
TI  - The value of postoperative MR in tethered cord: a review of 140 cases.
AB  - PURPOSE: This study aimed to determine the justification for routine
      postoperative MRI (POMR) following surgical release of tethered cord (TC) given
      that an MR, in this situation, mostly serves as a baseline and rarely has
      immediate clinical implications. Furthermore, later in the course of the disease,
      the presence of retethering is mostly assessed by clinical parameters, rather
      than imaging. METHODS: A single-center retrospective review of patients who
      underwent tethered cord release surgery between the years 1997 and 2009 at the
      Department of Pediatric Neurosurgery, Tel Aviv Medical Center, Israel was
      performed. Collected data including basis for diagnosis, pathology, associated
      clinical and radiologic findings, surgical procedure and outcome, postoperative
      follow-up and morbidities, and postoperative MRI findings were recorded and
      analyzed. RESULTS: One hundred forty patients operated upon between 1997 and 2009
      for tethered cord syndrome were reviewed. Routine postoperative MR was performed
      in all cases 6-18 months after surgery. All cases were fully untethered. MR
      revealed relevant information in eight cases, two with residual dermoid, and six
      with significant terminal syrinx. None of these findings led to repeat surgery or
      special treatment. Retethering operations were performed in two cases in which
      retethering was diagnosed based on clinical evaluation. CONCLUSIONS: Based on
      analysis of our series of 140 consecutive patients who all underwent POMR 6-18
      months after TC release, we suggest that POMR as routine clinical practice is not
      justified for uncomplicated cases of TC release. In cases of high risk for
      retethering, or significant preoperative syrinx or dermoid, POMR is recommended
      to establish a baseline for future clinical follow-up.

PMID- 21956778
TI  - Comment on: The value of post-operative MR in tethered cord: a review of 140
      cases by P. David Halevi, Suhas Udayakumaran, Liat Ben-Sira, Shlomi Constantini.

PMID- 21956779
TI  - Comment on: The value of post-operative MR in tethered cord: a review of 140
      cases by P. David Halevi, Suhas Udayakumaran, Liat Ben-Sira, Shlomi Constantini.

PMID- 21956780
TI  - Comment on: The value of post-operative MR in tethered cord: a review of 140
      cases by P. David Halevi, Suhas Udayakumaran, Liat Ben-Sira, Shlomi Constantini.

PMID- 21956781
TI  - Comment on: The value of post-operative MR in tethered cord: a review of 140
      cases by P. David Halevi, Suhas Udayakumaran, Liat Ben-Sira, Shlomi Constantini.

PMID- 21956782
TI  - Comment on: The value of post-operative MR in tethered cord: a review of 140
      cases by P. David Halevi, Suhas Udayakumaran, Liat Ben-Sira, Shlomi Constantini.

PMID- 21956783
TI  - Comment on: The value of post-operative MR in tethered cord: a review of 140
      cases by P. David Halevi, Suhas Udayakumaran, Liat Ben-Sira, Shlomi Constantini.

PMID- 21956784
TI  - Comment on: The value of post-operative MR in tethered cord: a review of 140
      cases by P. David Halevi, Suhas Udayakumaran, Liat Ben-Sira, Shlomi Constantini.

PMID- 21956785
TI  - Bilateral sciatic neuropathy as a complication of craniotomy performed in the
      sitting position: localization of nerve injury by using magnetic resonance
      imaging.
AB  - INTRODUCTION: Sciatic neuropathy is a rare but serious complication following
      surgery performed in the sitting position. METHODS: We report a case of a 12-year
      old boy who developed bilateral sciatic neuropathy after a 9-h-long craniotomy
      while in the sitting position. RESULTS: Magnetic resonance imaging for the lower
      extremities revealed bilateral swelling of the sciatic nerves near the ischial
      tuberosities. CONCLUSION: A heightened awareness of sciatic nerve injury during
      prolonged surgery in the sitting position may make early diagnosis possible and
      allow prevention of further neurologic injury.

PMID- 21956786
TI  - RXR antagonism induces G0 /G1 cell cycle arrest and ameliorates obesity by up
      regulating the p53-p21(Cip1) pathway in adipocytes.
AB  - The peroxisome proliferator activated receptor-gamma (PPARgamma) agonist,
      pioglitazone (PIO), exerts anti-diabetic properties associated with increased fat
      mass, whereas the retinoid X receptor (RXR) antagonist HX531 demonstrates anti
      obesity and anti-diabetic effects with reduced body weight and fat pad mass. The
      cell cycle abnormality in adipocytes has not been well-investigated in obesity or
      during treatment with modulators of nuclear receptors. We therefore investigated
      cell size and cell cycle distributions of adipocytes in vivo and examined the
      expression of cell cycle regulators in cultured human visceral preadipocytes. The
      cell size distribution and cell cycle analyses of in vivo adipocytes derived from
      OLETF rats demonstrated that HX531 brought about G0/G1 cell cycle arrest
      associated with the inhibition of cellular hypertrophy, which resulted in the
      reduction of fat pad mass. In contrast, PIO promoted proliferation activities
      associated with the increase in M + late M:G0 + G1 ratio and the appearance of
      both small and hypertrophied adipocytes. In cultured human visceral preadipocytes
      HX531 up-regulated cell cycle regulators, p53, p21(Cip1), cyclin D1, Fbxw7 and
      Skp2, which are known contributors towards G0 /G1 cell cycle arrest. The
      knockdown of p53 with a shRNA lentivirus reversed the HX531-induced up-regulation
      of p21(Cip1), which is one of the major p53-effector molecules. We conclude that
      HX531 exerts anti-obesity and anti-diabetes properties by up-regulating the p53
      p21(Cip1) pathway, resulting in G0/G1 cell cycle arrest and the inhibition of
      cellular hypertrophy of adipocytes.

PMID- 21956788
TI  - Grignard reagent acceleration of the intramolecular Diels-Alder reaction of
      furans with unactivated alkynes: towards structurally complex oxabicyclic
      alkenes.

PMID- 21956787
TI  - Muscarinic receptor activation enables persistent firing in pyramidal neurons
      from superficial layers of dorsal perirhinal cortex.
AB  - Persistent-firing neurons in the entorhinal cortex (EC) and the lateral nucleus
      of the amygdala (LA) continue to discharge long after the termination of the
      original, spike-initiating current. An emerging theory proposes that endogenous
      persistent firing helps support a transient memory system. This study
      demonstrated that persistent-firing neurons are also prevalent in rat perirhinal
      cortex (PR), which lies immediately adjacent to and is reciprocally connected
      with EC and LA. Several characteristics of persistent-firing neurons in PR were
      similar to those previously reported in LA and EC. Persistent firing in PR was
      enabled by the application of carbachol, a nonselective cholinergic agonist, and
      it was induced by injecting a suprathreshold current or by stimulating
      suprathreshold excitatory synaptic inputs to the neuron. Once induced, persistent
      firing lasted for seconds to minutes. Persistent firing could always be
      terminated by a sufficiently large and prolonged hyperpolarizing current; it was
      prevented by antagonists of muscarinic cholinergic receptors (mAChRs); and it was
      blocked by flufenamic acid. The latter has been suggested to inhibit a Ca(2+) 
      activated nonspecific cation conductance (G(CAN) ) that normally furnishes the
      sustained depolarization during persistent firing. In many PR neurons, the
      discharge rate during persistent firing was a graded function of depolarizing
      and/or hyperpolarizing inputs. Persistent firing was not prevented by blocking
      fast excitatory and inhibitory synaptic transmission, demonstrating that it can
      be generated endogenously. We suggest that persistent-firing neurons in PR, EC,
      LA, and certain other brain regions may cooperate in support of a transient
      memory system.

PMID- 21956789
TI  - Variations in the anatomy of the thyroid gland: clinical implications of a
      cadaver study.
AB  - Surgical removal of the thyroid gland is associated with risk of damage to the
      parathyroid glands, external branch of superior laryngeal nerves, inferior
      laryngeal nerves, and haematoma due to vascular damage and the chance of residual
      thyroid tissue being left in case of cancer and Graves' disease. The present
      study was designed to report the prevalence of anatomical variations and
      developmental anomalies of the thyroid gland that will hopefully help to minimise
      the aforementioned complications related to thyroid surgery. A total of 52 male
      and 18 female properly embalmed cadavers were dissected. The thyroid gland was
      examined for the presence of the pyramidal lobe, levator glandulae thyroideae and
      partial or complete absence of isthmus. Length, greatest transverse and
      anteroposterior extent of both the right and left lobe of the gland was recorded.
      A pyramidal lobe was present in 43.9% male and 22.2% female cadavers and was more
      prevalent on the left side of the median plane. Levator glandulae thyroideae was
      present in 34.6% male and 27.8% female cadavers. Isthmus was absent in 9.6% male
      and 5.6% female cadavers. The average length, greatest transverse and
      anteroposterior extent of right lobe was 4.43, 2.54 and 1.69 cm, respectively,
      whereas for the left lobe it was 4.21, 2.63 and 1.7 cm, respectively. The nature
      of the specimens studied, and the region where the study is carried out, affect
      the different goitre zones, age, sex, and race of population studied, all of
      which can contribute to the anatomical variations of the thyroid gland found in
      different reports by various authors.

PMID- 21956790
TI  - Two sides of the coin: the bully and the bullied.
AB  - Bullying has become a worldwide phenomenon that produces serious individual and
      societal consequences when it is ignored. There are two sides of the coin that
      require consideration when psychiatric-mental health (PMH) nurses conduct
      assessments of situations that involve bullying behaviors. Both the bully and the
      bullied can incur serious, negative, and debilitating psychological effects. In
      some cases, physical injury and/or death occurs as a result of bullying.
      Deciphering the biopsychosocial mental health issues associated with bullying is
      challenging. PMH nurses have the clinical expertise to develop coping
      interventions and strategies that stop bullying, as well as enhance the mental
      health and wellness of both those who bully and who are bullied. This article
      presents PMH nursing biopsychosocial strategies for both sides of the bullying
      coin. Exemplars are provided to aid implementation of the strategies.

PMID- 21956791
TI  - Understanding and assessing adverse drug reactions.
AB  - Establishing causality between a medication exposure and the development of an
      adverse event (AE) is a difficult process. If a causal relationship can be
      confirmed, an AE is referred to as an adverse drug reaction (ADR). The reported
      signs or symptoms of an AE could be due to the drug, the underlying disorder, or
      other unrelated or concurrent factors. The conventional approach to defining ADRs
      is based on a clinical judgment that the link between drug exposure and AE is
      definite, probable, possible, or doubtful. The validity and reliability of this
      assessment varies according to the knowledge, background, and experience of the
      clinician making the assessment. A systematic and validated method for estimating
      the probability of an ADR has been described by Naranjo et al. This method
      solicits answers to 10 questions; the total score is then used to quantify the
      probability of an ADR.

PMID- 21956792
TI  - Effects of exercise and physical activity on knee osteoarthritis.
AB  - Exercise is one of the most discussed and controversial nonpharmacologic
      management strategies for osteoarthritis (OA) of the knee. Health care providers
      and patients share varied and often pseudoscientific beliefs regarding the
      effects of exercise on knee OA formulated on outdated notions of the etiology,
      pathophysiology, and progression of the condition. Based on the contemporary
      literature, regular light to moderate physical activity has both preventive and
      therapeutic benefits for individuals with knee OA. Exercise regimens with strong
      evidence of benefit include those that focus on aerobic/cardiovascular
      conditioning and lower extremity strength training. Health care providers should
      confidently incorporate exercise recommendations into clinical management and
      offer patients evidence-based and individually tailored exercise prescriptions to
      help manage the painful and often disabling symptoms of this condition.

PMID- 21956793
TI  - Antimicrobial activity, bactericidal mechanism and LPS-neutralizing activity of
      the cell-penetrating peptide pVEC and its analogs.
AB  - pVEC is a cell-penetrating peptide derived from the murine vascular endothelial
      cadherin protein. To evaluate the potential of pVEC as antimicrobial peptide
      (AMP), we synthesized pVEC and its analogs with Trp and Arg/Lys substitution, and
      their antimicrobial and lipopolysaccharide (LPS)-neutralizing activities were
      investigated. pVEC and its analogs displayed a potent antimicrobial activity
      (minimal inhibitory concentration: 4-16 MUM) against Gram-positive and Gram
      negative bacteria but no or less hemolytic activity (less than 10% hemolysis)
      even at a concentration of 200 MUM. These peptides induced a near-complete
      membrane depolarization (more than 80%) at 4 MUM against Staphylococcus aureus
      and a significant dye leakage (35-70%) from bacterial membrane-mimicking liposome
      at a concentration as low as 1 MUM. The fluorescence profiles of pVEC and its
      analogs in dye leakage from liposome and membrane depolarization were similar to
      those of a frog-derived AMP, magainin 2. These results suggest that pVEC and its
      analogs kill bacteria by forming a pore or ion channel in the cytoplasmic
      membrane. pVEC and its analogs significantly inhibited nitric oxide production or
      tumor necrosis factor-alpha release in LPS-stimulated mouse macrophage RAW264.7
      cells at 10 to 50 MUM, in which RAW264.7 were not damaged. Taken together, our
      results suggest that pVEC and its analogs with potent antimicrobial and LPS
      neutralizing activities can serve as AMPs for the treatment of microbial
      infection and sepsis.

PMID- 21956795
TI  - Successful treatment of tabetic lightning pain and visceral crisis with
      gabapentin.

PMID- 21956794
TI  - Cognitive differences between patients with left-sided and right-sided
      Parkinson's disease. A review.
AB  - At disease onset, patients with Parkinson's disease (PD) typically report one
      side of the body to be more affected than the other. Previous studies have
      reported that this motor symptom asymmetry is associated with asymmetric
      dopaminergic degeneration in the brain. Research on the cognitive repercussions
      of this asymmetric degeneration has yielded inconsistent results. Here, we review
      studies that reported on the cognitive performance of patients with left-sided
      (LPD) or right-sided (RPD) motor symptom predominance. We present evidence that
      patients with RPD typically experience problems with language-related tasks and
      verbal memory, whereas patients with LPD more often perform worse on tasks of
      spatial attention, visuospatial orienting and memory and mental imagery. In
      general, no differences were found between both groups on tasks measuring
      attention and executive function. The association between motor asymmetry and
      cognitive performance indicates that PD does not lead to one typical cognitive
      profile. The effect of symptom laterality on the cognitive complaints should be
      considered in the assessment and treatment of each individual patient.

PMID- 21956796
TI  - Bioconjugated fluorescent zeolite L nanocrystals as labels in protein
      microarrays.
AB  - Zeolite L nanocrystals, as inorganic host material containing hydrophobic
      fluorophore N,N'-bis(2,6-dimethylphenyl)perylene-3,4,9,10-tetracarboxylic diimide
      in the unidirectional channels, are developed as new labels for biosensor
      systems. The external surface of the particles is modified with carboxylic acid
      groups for conjugation to primary amines of biomolecules such as antibodies. Anti
      digoxigenin (anti-DIG) is selected to be immobilized on zeolite L via N
      hydroxysulfosuccinimide ester linker. Together with DIG, it serves as a good
      universal binding pair for diverse analyte detection owing to the high binding
      affinity and low background noise. The conjugates are characterized by the
      dynamic light scattering technique for their hydrodynamic diameters and by enzyme
      linked immunosorbent assay for antigen-antibody binding behavior. The
      characterizations prove that anti-DIG antibodies are successfully immobilized on
      zeolite L with their binding activities maintained. The microarray fluorescent
      sandwich immunoassay based on such nanocrystalline labels shows high sensitivity
      in a thyroid-stimulating hormone assay with the lower detection limit down to the
      femtomolar range. These new fluorescent labels possess great potential for in
      vitro diagnostics applications.

PMID- 21956797
TI  - Association of B3GNT5 polymorphisms with susceptibility to ETEC F4ab/ac in the
      white Duroc * Erhualian intercross and 15 outbred pig breeds.
AB  - The B3GNT5 gene is a candidate for the F4ab/ac receptor conferring susceptibility
      to enterotoxigenic Escherichia coli (ETEC) F4ab/ac in pigs. In this study, we
      screened mutations in the complete coding region of the porcine B3GNT5 gene and
      identified four SNPs in the 3' untranslated regions. We genotyped the four SNPs
      across a large-scale White Duroc * Chinese Erhualian F2 resource population
      (total F2 = 755) and 292 purebred piglets representing 15 Chinese and Western
      breeds. We found that the g.1476G->A locus and haplotypes [A;T;G;T] and [A;G;G;T]
      had significant association with susceptibility to ETEC F4ac in the resource
      population. None of the B3GNT5 polymorphisms and haplotypes was associated with
      susceptibility to ETEC F4ab/ac in outbred piglets. This result, together with
      other reports, supports the conclusion that B3GNT5 is not the responsible gene
      encoding the ETEC F4ab/ac receptors.

PMID- 21956798
TI  - The chemistry and biology of trypanosomal trans-sialidases: virulence factors in
      Chagas disease and sleeping sickness.
AB  - trans-Sialidases constitute a special group of the sialidase family. They occur
      in some trypanosome species and, in a unique reversible reaction, transfer sialic
      acids from one glycosidic linkage with galactose (donor) to another galactose
      (acceptor), to form (alpha2-3)-sialyl linkages. Trypanosomes cause such
      devastating human diseases as Chagas disease in South America (Trypanosoma cruzi)
      or sleeping sickness in Africa (Trypanosoma brucei). The trans-sialidases
      strongly contribute to the pathogenicity of the trypanosomes by scavenging sialic
      acids from the host or blood meal to coat the parasite surface; this aids their
      survival strategy in the insect's intestine, and in the blood circulation or
      cells of the host, and serves to compromise the immune system of the human or
      animal host. American and African trypanosomes express trans-sialidases at
      different stages of their vector/host development. They are transmitted to humans
      by insect vectors (tsetse fly or other insect "bug" species). trans-Sialidase
      activity with varying linkage specificity has also been found in a few bacteria
      species and in human serum. trans-Sialidases are of increasing practical
      importance for the chemo-enzymatic synthesis of sialylated glycans. The search
      for appropriate inhibitors of trans-sialidases and vaccination strategies is
      intensifying, as less toxic medicaments for the treatment of these widespread and
      often chronic tropical diseases are required.

PMID- 21956799
TI  - Characterization of melanocortin receptors.
AB  - This unit describes a Scintillation Proximity Assay (SPA) for the measurement of
      ligand binding to melanocortin receptors (MCRs) using membranes prepared from
      cell lines stably expressing recombinant MCRs. It provides a facile method for
      determining the affinity of compounds at MC1R, MC3R, MC4R, or MC5R.

PMID- 21956800
TI  - Patch-clamp studies of human cardiac ion channels in the evaluation of cardiac
      electrophysiological effects of compounds.
AB  - Drugs prolonging the QT interval appear to consistently inhibit the outward,
      rapid delayed rectifier K+ current (IKr) conveyed by the HERG channel. Hence, for
      determining whether a new drug candidate blocks the latter channel, this unit
      presents a basic electrophysiology protocol to conduct patch clamp studies in
      single cell preparations expressing heterologously cloned HERG channels. An
      additional protocol details the isolation of myocytes from specimens of human
      atria which are used in the study of native cardiac ion currents (INa, ICa, Ito,
      Isus, IK1). The results of these tests are useful for determining whether drug
      candidates have the desired cardiac safety profile for human use.

PMID- 21956801
TI  - Respiratory function assessment in safety pharmacology.
AB  - The known effects of drugs from a variety of pharmacological/therapeutic classes
      on the respiratory system, the life-threatening consequences of respiratory
      dysfunction, and world-wide regulatory safety guidelines all support the need for
      conducting respiratory evaluations in safety pharmacology. This unit provides an
      overview of the functional disorders of the respiratory system and presents the
      techniques and strategies considered to be most appropriate for detecting and
      characterizing drug-induced respiratory disorders in safety pharmacology studies.

PMID- 21956802
TI  - Electrophysiological analysis of heterologously expressed Kv and SK/IK potassium
      channels.
AB  - This unit describes protocols to aid investigators in determining the
      electrophysiological and pharmacological profile of heterologously expressed
      voltage or calcium-activated potassium channels belonging to the Kv1.x and SK/IK
      gene families. Protocols for data acquisition as well as analysis are provided.

PMID- 21956803
TI  - Electrophysiological analysis of ATP-sensitive potassium channels in mammalian
      cells and Xenopus oocytes.
AB  - This unit describes general methodologies for the characterization of ATP
      sensitive K+ channels and the study of ligand-channel interactions in native
      tissues and clonal cell lines by electrophysiological techniques. Detailed
      protocols on how to establish patch-clamp single-channel and whole-cell current
      recording are presented. Two-electrode voltage clamp techniques for studying ATP
      sensitive K+ channels expressed in Xenopus oocytes are also included.

PMID- 21956804
TI  - Production and use of HIV-1 luciferase reporter viruses.
AB  - This unit describes the production and use of HIV-1 luciferase reporter viruses.
      These viruses are used to rapidly and accurately quantify HIV-1 in cell culture.
      Protocols are also presented for screening and characterization of small molecule
      inhibitors of HIV-1 entry into cells.

PMID- 21956805
TI  - Social recognition task in the rat.
AB  - Among the numerous tasks designed for assessing distinct memory processes, the
      social recognition task in the rat offers the opportunity to evaluate a form of
      short-term working memory in the domain of social cognition, and its modification
      by pharmacological agents or physiopathological states, such as aging. Social
      cognition in humans is obviously of great importance and its deficits, e.g.,
      during aging and Alzheimer's dementia, often have dramatic consequences for the
      patient and their environment. Two protocols are described in this unit that
      permit evaluation of positive and negative drug effects on social recognition
      memory in adult male rats and beneficial drug effects on age-related social
      recognition amnesia in aged male rats.

PMID- 21956806
TI  - Emetic liability testing in ferrets.
AB  - Evidence of a candidate drug's efficacy and safety is mandatory for successful
      drug registration by regulatory authorities. However, a third property,
      tolerability, often determines a drug's acceptance by the patient population.
      Gastrointestinal events often determine the maximum tolerated dose in Phase I
      clinical trials. If the plasma concentrations achieved at the maximum tolerable
      dose are below those required for efficacy, the drug will certainly fail. The
      identification of a compound's emetic/nauseogenic liability early in the
      discovery process can be critical to the ultimate success of the drug discovery
      project. Ferrets are small carnivores (~1 kg) of the Mustelidae family that vomit
      in response to many pharmacological classes of drugs as well as to cytotoxic
      chemotherapeutics and radiation. This unit describes a simple method for
      evaluating the emetic and nauseogenic potential of drug candidates in ferrets.

PMID- 21956807
TI  - Models of neuropathic pain in the rat.
AB  - Peripheral nerve injury due to trauma, disease, and certain toxins sometimes
      produces abnormal (neuropathic) pain syndromes that are chronic and refractory to
      standard analgesics. Knowledge of the mechanisms that produce neuropathic pain
      and the ability to search for new drugs to control it have been greatly advanced
      by the introduction of rat models of post-traumatic painful peripheral
      neuropathy. There are currently three models of neuropathic pain in the rat that
      are widely used. The procedures to create these models and the behavioral assays
      used to quantify the resulting neuropathic pain symptoms are described in this
      unit: the chronic constriction injury (CCI) model, the partial sciatic ligation
      (PSL) model, and the spinal nerve ligation (SNL) model. Four kinds of abnormal
      pain sensations are commonly measured to assess the outcome: heat-hyperalgesia,
      mechano-hyperalgesia, mechano-allodynia, and cold-allodynia.

PMID- 21956809
TI  - Overview of microarrays in drug discovery and development.
AB  - With the sequencing of the human genome, new tools and technologies have been
      developed to identify and quantify global gene-expression changes occurring in
      the cell. One of the main tools being utilized is microarray technology, which
      allows one to quantitate expression changes of thousands of genes in a single
      experiment. Microarrays allow researchers to gain an unprecedented understanding
      of the function and regulation of genes, and are transforming virtually all areas
      of biological research. In the drug-discovery process, microarrays have the
      potential to play a role in all stages, from new target discovery through
      compound profiling and safety assessment. This overview highlights some of these
      studies and discusses how this technology is transforming the field of drug
      discovery and development.

PMID- 21956808
TI  - Electrical amygdala kindling.
AB  - This unit describes a method of electrical amygdala kindling in the rat. This
      procedure requires mastery of stereotaxic electrode implantation which is not
      covered in the current unit. Also, the investigator must have a sound knowledge
      of electronics and computing. The text gives instructions on how to render rats
      epileptic, how to determine the effects of compounds in kindled rats, and how to
      analyze the data. Results with three reference substances are illustrated. These
      substances are used in the clinic and give robust results in kindling.

PMID- 21956810
TI  - Overview of electrophysiological characterization of neuronal nicotinic
      acetylcholine receptors.
AB  - Electrophysiology is one of the best tools to characterize ligand-gated channels
      such as neuronal nicotinic acetylcholine receptors. In this unit, the properties
      of these receptors are discussed along with approaches for how they can be
      characterized. Special emphasis is given to agonist and antagonist profiles as
      well as allosteric effectors that offer alternative possibilities in drug
      discovery.

PMID- 21956811
TI  - Electrophysiological analysis of tetrodotoxin-resistant sodium channel
      pharmacology.
AB  - This unit describes essential procedures to record the activity of and the
      effects of pharmacological manipulation upon tetrodotoxin-resistant (TTXr) sodium
      channels. Readers are guided through the process of assembling a functional
      |patch-clamp| electrophysiology apparatus and construction of software-controlled
      voltage protocols that address various aspects of channel gating. Guidelines are
      also presented for analysis and display of the data typically generated by these
      experiments. For investigators wishing to study native channels in their
      appropriate cellular environment, protocols describing the isolation of viable
      cells from the main tissues that commonly express TTXr channels are also
      included.

PMID- 21956812
TI  - Uptake studies for evaluating activity of efflux transporters in a cell line
      representative of the blood-brain barrier.
AB  - In this unit, protocols are presented for performing uptake studies with bovine
      brain microvessel endothelial cells (BBMECs) using either radiolabeled compounds,
      or rhodamine 123 as a marker for a P-glycoprotein substrate. The protocols can
      easily be modified for the investigation of substrate uptake in other cell lines.

PMID- 21956813
TI  - In vitro drug metabolism using liver microsomes.
AB  - Metabolic biotransformation of a drug can increase the rate of elimination from
      the body and have a significant effect on efficacy and safety. Drug candidates
      are screened early in the discovery process for metabolic stability using liver
      microsomes. Methods for microsome isolation and characterization and the
      determination of metabolic stability are presented.

PMID- 21956814
TI  - N-heterocyclic nitrenium ligands: a missing link explored.

PMID- 21956815
TI  - Competitive reactions of organophosphorus radicals on coke surfaces.
AB  - The efficacy of organophosphorus radicals as anticoking agents was subjected to a
      computational study in which a representative set of radicals derived from
      industrially relevant organophosphorus additives was used to explore competitive
      reaction pathways on the graphene-like coke surface formed during thermal
      cracking. The aim was to investigate the nature of the competing reactions of
      different organophosphorus radicals on coke surfaces, and elucidate their mode of
      attack and inhibiting effect on the forming coke layer by use of contemporary
      computational methods. Density functional calculations on benzene and a larger
      polyaromatic hydrocarbon, namely, ovalene, showed that organophosphorus radicals
      have a high propensity to add to the periphery of the coke surface, inhibiting
      methyl radical induced hydrogen abstraction, which is known to be a key step in
      coke growth. Low addition barriers reported for a phosphatidyl radical suggest
      competitive aptitude against coke formation. Moreover, organophosphorus additives
      bearing aromatic substituents, which were shown to interact with the coke surface
      through dispersive pi-pi stacking interactions, are suggested to play a
      nontrivial role in hindering further stacking among coke surfaces. This may be
      the underlying rationale behind experimental observation of softer coke in the
      presence of organophosphorus radicals. The ultimate goal is to provide
      information that will be useful in building single-event microkinetic models.
      This study presents pertinent information on potential reactions that could be
      taken up in these models.

PMID- 21956816
TI  - Molecular-beacon-based tricomponent probe for SNP analysis in folded nucleic
      acids.
AB  - Hybridization probes are often inefficient in the analysis of single-stranded DNA
      or RNA that are folded in stable secondary structures. A molecular beacon (MB)
      probe is a short DNA hairpin with a fluorophore and a quencher attached to
      opposite sides of the oligonucleotide. The probe is widely used in real-time
      analysis of specific DNA and RNA sequences. This study demonstrates how a
      conventional MB probe can be used for the analysis of nucleic acids that form
      very stable (T(m) > 80  degrees C) hairpin structures. Here we demonstrate that
      the MB probe is not efficient in direct analysis of secondary structure-folded
      analytes, whereas a MB-based tricomponent probe is suitable for these purposes.
      The tricomponent probe takes advantage of two oligonucleotide adaptor strands f
      and m. Each adaptor strand contains a fragment complementary to the analyte and a
      fragment complementary to a MB probe. In the presence of a specific analyte, the
      two adaptor strands hybridize to the analyte and the MB probe, thus forming a
      quadripartite complex. DNA strand f binds to the analyte with high affinity and
      unwinds its secondary structure. Strand m forms a stable complex only with the
      fully complementary analyte. The MB probe fluorescently reports the formation of
      the quadripartite associate. It was demonstrated that the DNA analytes folded in
      hairpin structures with stems containing 5, 6, 7, 8, 9, 11, or 13 base pairs can
      be detected in real time with the limit of detection (LOD) lying in the nanomolar
      range. The stability of the stem region in the DNA analyte did not affect the
      LOD. Analytes containing single base substitutions in the stem or in the loop
      positions were discriminated from the fully complementary DNA at room
      temperature. The tricomponent probe promises to simplify nucleic acid analysis at
      ambient temperatures in such applications as in vivo RNA monitoring, detection of
      pathogens, and single nucleotide polymorphism (SNP) genotyping by DNA
      microarrays.

PMID- 21956817
TI  - Amphiphilic peptides with arginine and valine residues as siRNA carriers.
AB  - An efficient and safe delivery carrier is required for the therapeutic
      application of siRNA. In this research, amphiphilic peptides with arginine and
      valine residues were evaluated as siRNA carriers. The peptides were composed of 1
      4 arginine-blocks and 6 valine-blocks. In the aqueous solution, the arginine
      valine peptides (RV peptides) formed micelles with hydrophobic cores comprised of
      a valine block and a cationic surface comprised of an arginine block. In a gel
      retardation assay, the RV peptides completely retarded siRNA at a 1:10 weight
      ratio (siRNA:peptide). A heparin competition assay suggested that the RV peptides
      formed more stable complexes with siRNA than they did with polyethylenimine (25
      kDa, PEI25k). In an in vitro silencing assay, a dual luciferase expression
      (Renilla and firefly luciferases) vector, psiCHECK2, was co-transfected into
      human embryonic kidney 293 cells with Renilla-siRNA using the RV peptides. The
      specific silencing effect of Renilla luciferase was analyzed in reference to
      firefly luciferase. The results showed that the R3V6 peptide was more efficient
      than the R1V6, R2V6, and R4V6 peptides in silencing Renilla luciferase. In the
      flow cytometry and in vitro silencing studies, the R3V6 peptide delivered Renila
      siRNA as efficiently as PEI25k. The siVEGF/R3V6 peptide also reduced endogenous
      vascular endothelial growth factor (VEGF) expression in CT27 cells as efficiently
      as PEI25k. A cytotoxicity assay showed that RV peptides did not cause any
      cytotoxicity. Therefore, RV peptides may be useful for the development of a safe
      and efficient delivery carrier of siRNA.

PMID- 21956818
TI  - Prevalence and risk factors for unsuspected spontaneous ascitic fluid infection
      in cirrhotics undergoing therapeutic paracentesis in an outpatient clinic.
AB  - BACKGROUND: Spontaneous bacterial peritonitis (SBP) has been typically described
      in hospitalized patients. There are little data on ascitic fluid infection in
      asymptomatic outpatients. The present study was aimed at determining the
      prevalence and risk factors for asymptomatic ascitic fluid infection among
      patients with liver cirrhosis attending an outpatient clinic. METHODS: Between
      January 2008 and December 2009, consecutive patients with cirrhosis (n = 110)
      undergoing therapeutic paracentesis in an outpatient setting were studied.
      Patients with fever, abdominal pain, hepatic encephalopathy, recent
      gastrointestinal bleeding, impaired renal function, previous history of SBP and
      on antibiotic treatment were excluded. Baseline demographic details, and etiology
      and severity of liver disease were recorded. Ascitic fluid cell count, culture
      and biochemical tests were done using standard laboratory techniques. RESULTS:
      The causes of cirrhosis were alcohol (55.5%), hepatitis B (21.8%), hepatitis C
      (9.1%) and others (13.6%). A total of 278 paracenteses were done in them (average
      2.5 [1.1] times per patient). Spontaneous ascitic fluid infection was found in 7
      (2.5%) paracentesis, including spontaneous bacterial peritonitis in one (0.4%),
      monomicrobial nonneutrocytic bacterascites (MNB) in two (0.7%) and culture
      negative neutrocytic ascites (CNNA) in four (1.4%). Escherichia coli, Klebsiella
      spp. and Staphylococcus aureus were grown. There was no difference between
      cirrhotic outpatients with and without infection in age, gender, alcohol
      consumption, etiology of cirrhosis, Child-Pugh score, serum albumin and ascitic
      fluid total protein. There was no death due to spontaneous ascitic fluid
      infection. CONCLUSION: Asymptomatic ascitic fluid infection was very infrequent
      in patients with cirrhosis attending an outpatient clinic and undergoing
      therapeutic paracentesis.

PMID- 21956819
TI  - Atypical marginal zone hyperplasia of tonsil with immunoglobulin light chain
      restriction.

PMID- 21956820
TI  - Relationship between symptoms of depression and agitation in nursing home
      residents with dementia.
AB  - OBJECTIVE: The aim of this study is to analyze modifiable factors related to
      agitation of nursing home residents with dementia. METHODS: Relationship of
      agitation with three modifiable factors (depression, psychosis, and pain) was
      explored using longitudinal Minimum Data Set (MDS) information from 2032
      residents of Dutch nursing homes. Presence of agitation and depression was
      ascertained using validated scales based on MDS information. Presence of
      psychosis and pain was ascertained from the individual MDS items. RESULTS: There
      was a significant correlation between MDS depression and agitation scores.
      Depression scores increased in residents whose agitation worsened and decreased
      in residents whose agitation improved. Psychosis scores (combination of delusions
      and hallucinations) also correlated with MDS depression scores, and psychosis
      scores increased in residents whose agitation worsened. Pain scores correlated
      with agitation scores, but the pain scores did not change with changes in
      agitation. Depression symptoms were present in 51% of residents, while psychotic
      symptoms were present only in 15% of residents, and two-thirds of these residents
      were also depressed. CONCLUSION: These results indicate that depression may be
      the most common factor associated with agitation in nursing home residents with
      dementia.

PMID- 21956821
TI  - Memory erasure by very high concentrations of ZIP may not be due to PKM-zeta.

PMID- 21956822
TI  - Specific targeting of hypoxic tumor tissue with nitroimidazole-peptide
      conjugates.

PMID- 21956823
TI  - The Fanconi anaemia pathway orchestrates incisions at sites of crosslinked DNA.
AB  - Fanconi anaemia (FA) is a rare, autosomal recessive, genetically complex, DNA
      repair deficiency syndrome in man. Patients with FA exhibit a heterogeneous
      spectrum of clinical features. The most significant and consistent phenotypic
      characteristics are stem cell loss, causing progressive bone marrow failure and
      sterility, diverse developmental abnormalities and a profound predisposition to
      neoplasia. To date, 15 genes have been identified, biallelic disruption of any
      one of which results in this clinically defined syndrome. It is now apparent that
      all 15 gene products act in a common process to maintain genome stability. At the
      molecular level, a fundamental defect in DNA repair underlies this complex
      phenotype. Cells derived from FA patients spontaneously accumulate broken
      chromosomes and exhibit a marked sensitivity to DNA-damaging chemotherapeutic
      agents. Despite complementation analysis defining many components of the FA DNA
      repair pathway, no direct link to DNA metabolism was established until recently.
      First, it is now evident that the FA pathway is required to make incisions at the
      site of damaged DNA. Second, a specific component of the FA pathway has been
      identified that regulates nucleases previously implicated in DNA interstrand
      crosslink repair. Taken together, these data provide genetic and biochemical
      evidence that the FA pathway is a bona fide DNA repair pathway that directly
      mediates DNA repair transactions, thereby elucidating the specific molecular
      defect in human Fanconi anaemia.

PMID- 21956824
TI  - Efficient total synthesis of marine alkaloid (-)-nakadomarin A.

PMID- 21956825
TI  - [Neuroendocrine immunology: new pathogenetic aspects and clinical application].
AB  - After two decades of enormous improvements in anti-inflammatory therapy with
      biologics long-standing disease sequelae in chronic inflammatory diseases (CID)
      can be recognized, such as fatigue, anorexia/malnutrition, cachectic obesity,
      insulin resistance, dyslipidemia, changes of steroid hormone axes (e. g. loss of
      androgens), increased sympathetic nervous tone/decreased parasympathetic nervous
      tone, inflammation-related anemia and osteopenia. This article demonstrates for
      the first time in the German language a new theory to explain the pathophysiology
      of these disease sequelae. It includes concepts from evolutionary medicine and
      neuroendocrine regulation of energy allocation. The core statement is: the
      networks of energy regulation and energy allocation have been evolutionarily
      positively selected for transient inflammatory episodes (not for CIDs due to the
      negative selection pressure) but long-standing use of these adaptive programs for
      CID support systemic disease sequelae. These considerations might help to deviate
      focus from pure anti-inflammatory treatment to adequate diagnosis and therapy of
      systemic disease sequelae.

PMID- 21956826
TI  - [DNA microarrays].
AB  - Since their development in the 1990s DNA microarrays have advanced to one of the
      most important technologies for biomedical research. Miniaturization enables up
      to 1 million different sequence-specific DNA hybridization tests to be performed
      on an area of less than 2 cm2. Depending on the selection of oligonucleotide
      sequences, which are assembled on a microarray and on the treatment of samples
      prior to hybridization, up to genome-wide analyses for genotypes, gene
      expression, epigenetic changes or promoter activation can be performed.
      Increasing knowledge about the human genome advances commercial pre-assembly of
      DNA microarrays with selected oligonucleotide sequences for specialized
      applications. In clinical rheumatology gene expression analyses in treatment
      studies are of increasing importance. Similarly, this technique also identified
      new biomarkers that allow even better assessment of the current disease activity.
      The varieties of application enable the possibility of systematic research on the
      immunological response to specific patterns after stimulation. This opens up
      opportunities to detect and differentiate immunological reaction patterns better.

PMID- 21956827
TI  - [Prophylaxis and treatment of osteoporosis in patients with rheumatoid arthritis
      (ORA study)].
AB  - OBJECTIVE: The aim of this study was to examine bone mineral density (BMD),
      frequency of osteopenia and osteoporosis in a representative sample of patients
      with rheumatoid arthritis (RA) and to describe chemoprophylaxis and treatment of
      osteoporosis compared to evidence-based guidelines. PATIENTS AND METHODS: In 2005
      and 2006, 532 patients with RA (98 men, 434 women) aged 23-87 years were
      recruited from 9 German rheumatology centers. Clinical examination included a
      detailed documentation of osteoporosis medication. Dual-energy X-ray
      absorptiometry (DXA) was used to measure BMD at the lumbar spine and femoral
      neck. Osteopenia and osteoporosis were defined according to the criteria of the
      World Health Organization. RESULTS: Of the RA patients 29% had normal BMD at the
      spine and femoral neck, 49% of the patients had osteopenia and 22% met the
      criteria for osteoporosis at any site. Of the patients 60% were receiving
      medication for prophylaxis or therapy of osteoporosis, 38% calcium/vitamin D
      alone, 20% as combinations mostly of calcium/vitamin D + bisphosphonate, 1%
      received bisphosphonate only and 1% hormone replacement therapy. Although the
      frequency of osteoporosis showed no significant differences between male and
      female patients, women with RA used osteoporosis medication more often than men
      (63% versus 49%, chi2-test, p <0.05). A total of 101 RA patients (83 menopausal
      women, 6 premenopausal women, 12 men) received corticosteroids in a daily dose of
      7.5 mg or less for at least 3 months and had DXA T-scores below -2.0 at any site.
      In this patient group 41% of the menopausal women, 17% of the premenopausal women
      and 42% of the male patients were reported to receive medication with
      calcium/vitamin D + bisphosphonate. Calcium/vitamin D was used by 35% of the
      menopausal women, none of the premenopausal women and 50% of the male patients
      and 18% of the menopausal women, 67% of the premenopausal women and 8% of men
      received no prophylaxis or treatment for osteoporosis. CONCLUSION: According to
      the DVO (German Society for Osteoporosis) guidelines for osteoporosis (2009)
      menopausal women with corticosteroid therapy < 7.5 mg per day for at least 3
      months and DXA T-scores below -2.0 should receive treatment with bisphosphonate
      and calcium/vitamin D. The data show that there were still deficits concerning
      prophylaxis and treatment of osteoporosis in RA.

PMID- 21956828
TI  - [Prescription of TNF-alpha inhibitors and regional differences in 2010].
AB  - Tumor necrosis factor alpha (TNF-alpha) inhibitors are an important treatment
      option for rheumatoid arthritis and other chronic inflammatory diseases. However,
      attention should be paid to severe adverse drug reactions and very high costs of
      therapy. The objective of this study was to examine the prescription and costs of
      TNF-alpha inhibitors as well as regional differences at the district level in
      Germany. For this purpose, prescription claims data of a German health fund with
      9.1 million insured persons from the year 2010 were analyzed. A total of 45,229
      packs (0.1% of all prescribed drugs) and 3.15 million defined daily doses (DDD)
      of TNF-alpha inhibitors were prescribed. This leads to a total pharmacy revenue
      of 163.18 million Euro (share 4.1%) and 1 DDD costs on average 51.61 Euro. For
      10,078 patients at least one TNF inhibitor was prescribed (prescription
      prevalence 111 per 100,000) with a higher proportion of women (125 vs. 92 per
      100,000). The average revenue per insured person was often higher in districts of
      eastern Germany (>30 Euro) for reasons unknown. Provided that use is appropriate
      to indications there are only low saving potentials.

PMID- 21956829
TI  - The anthropoid-like face of Siamopithecus: cherry picking trees, phylogenetic
      corroboration, and the adapiform-anthropoid hypothesis.

PMID- 21956830
TI  - Identification and characterization of two novel antimicrobial peptides, temporin
      Ra and temporin-Rb, from skin secretions of the marsh frog (Rana ridibunda).
AB  - In this study, two novel antimicrobial peptides from the skin secretions of the
      marsh frog, Rana ridibunda, named temporin-Ra and temporin-Rb, were identified
      and purified using RP-HPLC. Temporin-Ra and temporin-Rb are composed of 14 and 12
      amino acids, respectively. Our results show that these peptides have inhibitory
      effects on both gram-negative and gram-positive bacteria, especially antibiotic
      resistant strains prevalent in hospitals, such as Staphylococcus aureus and
      Streptococcus agalactiae. The sequences and molecular weights of these peptides
      were determined using tandem MS. The molecular masses were found to be 1242.5 Da
      for temporin-Rb and 1585.1 Da for temporin-Ra. Human red blood cells tolerated
      well exposure to temporin-Ra and temporin-Rb, which, at a concentration of 60
      ug/ml, induced 1.3% and 1.1% hemolysis, respectively. MIC values of these
      peptides are suitable for potent antimicrobial peptides. The low hemolytic effect
      and wide-spectrum antimicrobial activity suggest a possible therapeutic
      application of these novel peptides.

PMID- 21956831
TI  - Combined antidepressant strategies are not more effective than vigorous
      escitalopram monotherapy: results of the CO-MED study.

PMID- 21956832
TI  - Characterization of cucumber vein-clearing virus, a whitefly (Bemisia tabaci G.)
      transmitted carlavirus.

PMID- 21956834
TI  - Inhibition of Escherichia coli and Proteus mirabilis adhesion and biofilm
      formation on medical grade silicone surface.
AB  - Silicone has been utilized extensively for biomedical devices due to its
      excellent biocompatibility and biodurability properties. However, its surface is
      easily colonized by bacteria which will increase the probability of nosocomial
      infection. In the present work, a hydrophilic antimicrobial carboxymethyl
      chitosan (CMCS) layer has been grafted on medical grade silicone surface pre
      treated with polydopamine (PDA). The increase in hydrophilicity was confirmed
      from contact angle measurement. Bacterial adhesion tests showed that the PDA-CMCS
      coating reduced the adhesion of Escherichia coli and Proteus mirabilis by >= 90%.
      The anti-adhesion property was preserved even after the aging of the
      functionalized surfaces for 21 days in phosphate-buffered saline (PBS), and also
      after autoclaving at 121 degrees C for 20 min. Both E. coli and P. mirabilis
      readily form biofilms on the pristine surface under static and flow conditions
      but with the PDA-CMCS layer, biofilm formation is inhibited. The flow experiments
      indicated that it is more difficult to inhibit biofilm formation by the highly
      motile P. mirabilis as compared to E. coli. No significant cytotoxicity of the
      modified substrates was observed with 3T3 fibroblasts.

PMID- 21956835
TI  - Dehydrogenative Heck reaction of furans and thiophenes with styrenes under mild
      conditions and influence of the oxidizing agent on the reaction rate.

PMID- 21956833
TI  - Vitamin D insufficiency is prevalent and vitamin D is inversely associated with
      parathyroid hormone and calcitriol in pregnant adolescents.
AB  - Few large studies have assessed changes in calcitropic hormones and maternal 25
      hydroxyvitamin D (25(OH)D) status across pregnancy, and how this may impact
      maternal bone turnover and neonatal hormone status. We aimed to identify
      determinants of 25(OH)D, parathyroid hormone (PTH), and calcitriol across
      pregnancy in a longitudinal study of 168 pregnant adolescents (<=18 years of
      age). Maternal 25(OH)D, PTH, and calcitriol were assessed at mid-gestation (~26
      weeks), delivery, and in cord blood. Data were related to measures of maternal
      anthropometrics, dietary intake, physical activity, and bone turnover markers.
      Approximately 50% of teens and their infants had serum 25(OH)D <= 20 ng/mL;
      25(OH)D was lower in African Americans versus whites (p < 0.001). PTH increased
      across gestation (p < 0.001). Elevated PTH (>=60 pg/mL) was detected in 25% of
      adolescents at delivery, and was associated with increased concentrations of
      serum N-telopeptide (NTX) (p = 0.028). PTH and calcitriol did not significantly
      differ across the range of Ca intake consumed (257-3220 mg/d). In the group as a
      whole, PTH was inversely associated with 25(OH)D in maternal circulation at mid
      gestation (p = 0.023) and at delivery (p = 0.019). However, when the cohort was
      partitioned by 25(OH)D status, this relationship was only present in those with
      25(OH)D <= 20 ng/mL, suggestive of a threshold below which 25(OH)D impacts PTH
      during pregnancy. Mid-gestation 25(OH)D was inversely associated with calcitriol
      at delivery (p = 0.023), irrespective of Ca intake. Neonatal PTH and calcitriol
      were significantly lower than (p < 0.001), but unrelated to maternal
      concentrations. These findings indicate that maternal 25(OH)D status plays a role
      in calcitropic hormone regulation in pregnant adolescents.

PMID- 21956838
TI  - Synthesis, structure, and glutathione peroxidase-like activity of amino acid
      containing ebselen analogues and diaryl diselenides.
AB  - The synthesis of some ebselen analogues and diaryl diselenides, which have amino
      acid functions as an intramolecularly coordinating group (Se...O) has been
      achieved by the DCC coupling procedure. The reaction of 2,2'-diselanediylbis(5
      tert-butylisophthalic acid) or the activated ester tetrakis(2,5-dioxopyrrolidin-1
      yl) 2,2'-diselanediylbis(5-tert-butylisophthalate) with different C-protected
      amino acids (Gly, L-Phe, L-Ala, and L-Trp) afforded the corresponding ebselen
      analogues. The used precursor diselenides have been found to undergo facile
      intramolecular cyclization during the amide bond formation reaction. In contrast,
      the DCC coupling of 2,2'-diselanediyldibenzoic acid with C-protected amino acids
      (Gly, L/D-Ala and L-Phe) affords the corresponding amide derivatives and not the
      ebselen analogues. Some of the representative compounds have been structurally
      characterized by single-crystal X-ray crystallography. The glutathione peroxidase
      (GPx)-like activities of the ebselen analogues and the diaryl diselenides have
      been evaluated by using the coupled reductase assay method. Intramolecularly
      stabilized ebselen analogues show slightly higher maximal velocity (V(max)) than
      ebselen. However, they do not show any GPx-like activity at low GSH
      concentrations at which ebselen and related diselenides are active. This could be
      attributed to the peroxide-mediated intramolecular cyclization of the
      corresponding selenenyl sulfide and diaryl diselenide intermediates generated
      during the catalytic cycle. Interestingly, the diaryl diselenides with alanine
      (L,L or D,D) amide moieties showed excellent catalytic efficiency (k(cat)/K(M))
      with low K(M) values in comparison to the other compounds.

PMID- 21956837
TI  - Cell targeting with hybrid Qbeta virus-like particles displaying epidermal growth
      factor.
AB  - Structurally uniform protein nanoparticles derived from the self-assembly of
      viral capsid proteins are attractive platforms for the multivalent display of
      cell-targeting motifs for use in nanomedicine. Virus-based nanoparticles are of
      particular interest because the scaffold can be manipulated both genetically and
      chemically to simultaneously display targeting groups and carry a functional
      payload. Here, we displayed the human epidermal growth factor (EGF) on the
      exterior surface of bacteriophage Qbeta as a C-terminal genetic fusion to the
      Qbeta capsid protein. The co-assembly of wild-type Qbeta and EGF-modified
      subunits resulted in structurally homogeneous nanoparticles displaying between 5
      and 12 copies of EGF on their exterior surface. The particles were found to be
      amenable to bioconjugation by standard methods as well as the high-fidelity
      copper-catalyzed azide-alkyne cycloaddition reaction (CuAAC). Such chemical
      derivatization did not impair the ability of the particles to specifically
      interact with the EGF receptor. Additionally, the particle-displayed EGF remained
      biologically active promoting autophosphorylation of the EGF receptor and
      apoptosis of A431 cells. These results suggest that hybrid Qbeta-EGF
      nanoparticles could be useful vehicles for targeted delivery of imaging and/or
      therapeutic agents.

PMID- 21956839
TI  - Interaction of Wnt/beta-catenin and notch signaling in the early stage of cardiac
      differentiation of P19CL6 cells.
AB  - Notch and Wnt/beta-catenin signaling both play essential roles and interact
      closely in cardiomyocyte differentiation but the mechanism of interaction is
      largely unknown. Here we show that activation of Notch signaling in
      undifferentiated P19CL6 cells promoted cardiac differentiation, indicated by
      upregulated expression of early cardiac markers and activated the canonical Wnt
      pathway, suggested by augmented nuclear translocation of beta-catenin. Further
      activation of the Notch pathway in early differentiating cells (at day 3)
      inhibited expression of a specific cardiac progenitor marker Islet1 but had no
      influence on beta-catenin translocation. Notch signaling thus played biphasic
      roles in the early stage of cardiomyocyte differentiation and Wnt/beta-catenin
      signaling. Unlike Notch signaling, Wnt signaling promoted cardiomyocyte
      differentiation and activated the Notch pathway in either undifferentiated or
      early differentiating cells. Additionally, beta-catenin, recombination signal
      sequence binding protein-Jkappa (RBP-Jkappa), and Notch1 intracellular domain
      (NICD-1) formed a transcriptional complex which was recruited to the Hes1
      promoter region, indicating direct transcriptional regulation of Hes1. We thus
      document a specific reciprocal interaction between these two signaling pathways
      during early stage cardiac differentiation of P19CL6 cells.

PMID- 21956840
TI  - Surface ultrastructure of the gill filaments and the secondary lamellae of the
      catfish, Rita rita, and the carp, Cirrhinus mrigala.
AB  - Surface ultrastructures of gill filaments and secondary lamellae of Rita rita and
      Cirrhinus mrigala, inhabiting different ecological habitat, were investigated to
      unravel adaptive modifications. R. rita is a sluggish, bottom dwelling
      carnivorous catfish, which inhabits regions of river with accumulations of dirty
      water. It retains its viability for long time if taken out of water. C. mrigala
      is an active bottom dwelling Indian major carp, which lives in relatively clean
      water and dies shortly after taken out of water. In R. rita, gill septa between
      gill filaments are reduced. Microridges on epithelial cells covering gill
      filaments are often continuous and arranged concentrically. Secondary lamellae
      are extensive. The epithelium appears corrugated, show irregular elevations and
      shallow depressions, and microridges on epithelial cells appear fragmented. In C.
      mrigala, in contrast, the gill septa are extensive. Microridges on epithelial
      cells covering gill filaments are fragmented. Secondary lamellae are less
      extensive. The epithelium appears smooth and microridges on epithelial cells are
      relatively inconspicuous. These differences have been considered adaptive
      modification in relation to habit and ecological niches inhabited by two fish
      species. Presence of mucous goblet cells on gill filaments is discussed in
      relation to their functions including precipitation of the sediments and
      preventing clogging of gill filaments. Infrequent mucous goblet cells in the
      epithelium of secondary lamellae in two fish species are considered an
      adaptation, minimizing thickness of the epithelium to reduce barrier between
      blood and water for favoring gasses exchange with increased efficiency.

PMID- 21956841
TI  - Fatal disseminated intravascular coagulation in acute promyelocytic leukemia.

PMID- 21956843
TI  - An evaluation of UiO-66 for gas-based applications.
AB  - In addition to its high thermal stability, repetitive hydration/dehydration tests
      have revealed that the porous zirconium terephthalate UiO-66 switches reversibly
      between its dehydroxylated and hydroxylated versions. The structure of its
      dehydroxylated form has thus been elucidated by coupling molecular simulations
      and X-ray powder diffraction data. Infrared measurements have shown that
      relatively weak acid sites are available while microcalorimetry combined with
      Monte Carlo simulations emphasize moderate interactions between the UiO-66
      surface and a wide range of guest molecules including CH(4), CO, and CO(2). These
      properties, in conjunction with its significant adsorption capacity, make UiO-66
      of interest for its further evaluation for CO(2) recovery in industrial
      applications. This global approach suggests a strategy for the evaluation of
      metal-organic frameworks for gas-based applications.

PMID- 21956842
TI  - Epiphyseal growth plate and secondary peripheral chondrosarcoma: the neighbours
      matter.
AB  - Chondrocytes interact with their neighbours through their cartilaginous
      extracellular matrix (ECM). Chondrocyte-matrix interactions compensate the lack
      of cell-cell contact and are modulated by proteoglycans and other molecules. The
      epiphyseal growth plate is a highly organized tissue responsible for long bone
      elongation. The growth plate is regulated by gradients of morphogens that are
      established by proteoglycans. Morphogens diffuse across the ECM, creating short-
      and long-range signalling that lead to the formation of a polarized tissue.
      Mutations affecting genes that modulate cell-matrix interactions are linked to
      several human disorders. Homozygous mutations of EXT1/EXT2 result in reduced
      synthesis and shortened heparan sulphate chains on both cell surface and matrix
      proteoglycans. This disrupts the diffusion gradients of morphogens and signal
      transduction in the epiphyseal growth plate, contributing to loss of cell
      polarity and osteochondroma formation. Osteochondromas are cartilage-capped bony
      projections arising from the metaphyses of endochondral bones adjacent to the
      growth plate. The osteochondroma cap is formed by cells with homozygous mutation
      of EXT1/EXT2 and committed stem cells/wild-type chondrocytes. Osteochondroma
      serves as a niche (a permissive environment), which facilitates the committed
      stem cells/wild-type chondrocytes to acquire secondary genetic changes to form a
      secondary peripheral chondrosarcoma. In such a scenario, the micro-environment is
      the site of the initiating processes that ultimately lead to cancer.

PMID- 21956844
TI  - DNA methylation and nonsmall cell lung cancer.
AB  - Lung cancer is the leading cause of cancer-related death in men and women
      worldwide. Owing to the scarcity of effective tools for early detection and
      therapy strategies, the 5-year survival rate of lung cancer is very poor. Because
      the accumulation of multiple genetic and/or epigenetic changes, including DNA
      methylation, has been suggested to contribute to development and progression of
      human cancers, improved understanding of the relationship between DNA methylation
      and lung cancer will provide new insights for identifying promising biomarkers
      for diagnosis, prognosis, and treatment of lung cancer. Here, we present a
      relatively comprehensive review of DNA methylation and lung cancer, discuss DNA
      methylation changes in carcinogenesis and metastasis of lung cancer, and explore
      the association of microRNA with DNA methylation. Additionally, we outline the
      applications of DNA methylation in clinical practice, such as diagnosis,
      prognosis, and therapy of lung cancer.

PMID- 21956845
TI  - One-pot nonreductive O-glycan release and labeling with 1-phenyl-3-methyl-5
      pyrazolone followed by ESI-MS analysis.
AB  - A novel one-pot procedure for the nonreductive release of O-linked glycans from
      glycoproteins and the simultaneous derivatization of released glycans with 1
      phenyl-3-methyl-5-pyrazolone (PMP) is described. Unlike the traditional reductive
      beta-elimination, which produces alditols, this new method employs PMP/ammonia
      aqueous solution as the reaction medium. The O-glycans are released from
      glycoproteins and derivatized with PMP nonreductively, specifically, and
      quantitatively. Samples can be easily purified from ammonia, excess PMP, and
      peptide residues by evaporation, chloroform extraction, and solid-phase
      extraction (SPE) column fractionation for HPLC, CE, or MS analysis. The procedure
      has been elaborated with two purified glycoproteins, porcine stomach mucin and
      bovine fetuin, and successfully applied to O-glycan profiling of a challenging
      biological specimen, healthy human plasma. This new procedure has shown
      methodological significance in O-glycan analysis.

PMID- 21956849
TI  - The GPR17 receptor in NG2 expressing cells: focus on in vivo cell maturation and
      participation in acute trauma and chronic damage.
AB  - NG2-expressing cells comprise a population of cycling precursors that can exit
      the cell cycle and differentiate into mature oligodendrocytes. As a whole, they
      display heterogeneous properties and behaviors that remain unresolved at the
      molecular level, although partly interpretable as distinct maturation stages. To
      address this issue, we analyzed the expression of the GPR17 receptor, recently
      shown to decorate NG2-expressing cells and to operate as an early sensor of brain
      damage, in immature and adult oligodendrocyte progenitors in the intact brain and
      after injury. In both the early postnatal and adult cerebral cortex, distinct
      GPR17 protein localizations and expression levels define different stages of
      oligodendroglial maturation, ranging from the precursor phase to the
      premyelinating phenotype. As soon as cells exit mitosis, a fraction of NG2
      expressing cells displays accumulation of GPR17 protein in the Golgi apparatus.
      GPR17 expression is subsequently upregulated and distributed to processes of
      cells that stop dividing, progressively lose NG2 positivity and assume
      premyelinating features. Absence of colabeling with mature markers or myelin
      proteins indicates that GPR17 is downregulated when cells complete their final
      maturation. BrdU-based fate-mapping demonstrated that a significant fraction of
      newly generated oligodendrocyte progenitors transiently upregulates GPR17 during
      maturation. Importantly, we also found that GPR17 does not participate to the
      early reaction of NG2-expressing cells to damage, while it is induced at
      postacute stages after injury. These findings identify GPR17 as a marker for
      progenitor progression within the oligodendroglial lineage and highlight its
      participation to postacute reactivity of NG2 cells in different injury paradigms.

PMID- 21956850
TI  - Aerobic lactonization of diols by biomimetic oxidation.

PMID- 21956851
TI  - A DFT study of carbon in the subsurface layer of cobalt surfaces.

PMID- 21956852
TI  - Protein alpha-turns recreated in structurally stable small molecules.

PMID- 21956853
TI  - Histopathology of the Ex-PRESS Shunt.
AB  - The authors report the histopathologic features of a human enucleated eye with an
      Ex-PRESS shunt (Optonol, Ltd., Neve Ilan, Israel). An 86-year-old man with a
      blind painful eye underwent enucleation. He had a history of glaucoma with an Ex
      PRESS shunt implanted. Histopathologic evaluation of the specimen showed a thin
      layer of fibrotic tissue surrounding the implant. In this case, the Ex-PRESS
      shunt was relatively well tolerated in the human eye.

PMID- 21956854
TI  - High-definition optical coherence tomography features of primary vitreoretinal
      lymphoma.
AB  - Primary vitreoretinal lymphoma is a high-grade intraocular malignancy that
      presents as a vitritis with creamy subretinal lesions. In cases where the
      vitritis is dense, the characteristic subretinal lesions can be difficult to see
      on clinical examination. Novel high-definition imaging techniques that allow for
      deeper penetration through opaque media could have diagnostic utility in such
      cases. The authors present a case of a patient who presented with a dense
      vitritis that precluded visualization of fundus details. Spectral-domain optical
      coherence tomography using high-definition raster imaging demonstrated subretinal
      deposits along with outer retinal atrophy. These findings were suggestive of
      primary vitreoretinal lymphoma and prompted diagnostic vitrectomy. Pathological
      examination of the vitreous specimen confirmed the diagnosis of primary
      vitreoretinal lymphoma.

PMID- 21956855
TI  - Antennal sensory structures in Scaphoideus titanus Ball (Hemiptera:
      Cicadellidae).
AB  - Scaphoideus titanus Ball (Hemiptera: Cicadomorpha) is a leafhopper vector of a
      phytoplasma disease, the Flavescence doree (FD), belonging to the vine yellows
      group. A scanning and transmission electron microscope study has been carried out
      to investigate the antennal sensory structures. The first two segments, the scape
      and the pedicel, are short, covered by cuticular scales and devoid of sensilla,
      with exception of some scattered hairs on the pedicel. The flagellum consists of
      a unique, elongated segment in which numerous subunits can be recognized, being
      separated by a sort of cuticular crown. The proximal five subunits bear most of
      the sensilla. We discovered the presence of single- and double-walled coeloconic
      sensilla, campaniform sensilla, basiconic sensilla, and trichoid sensilla. A
      scolopidium is located within the proximal region of the flagellum.
      Ultrastructural investigations suggest that the antennal sensilla could be
      involved in the perception of air-borne vibrations, temperature, and humidity
      variations. The most relevant feature is the extreme reduction of the olfactory
      sensilla, both in terms of number of sensory structures and sensory neurons per
      sensillum. The strong reduction in antennal olfactory sensilla to which this
      specie has undergone is discussed as possible consequence of the specificity
      toward the host plant.

PMID- 21956856
TI  - In situ follicular lymphoma associated with overt B- or T-cell lymphomas in the
      same lymph node.
AB  - In situ follicular lymphoma (FL) is usually an incidental finding in otherwise
      reactive lymph node [1-3]. However, it may be associated with overt FL, or with
      lymphomas other than FL or with other malignancies,in other sites or, less
      commonly, in the same lymph node [2,4-8]. Here we describe two cases of in situ
      FL, one with concurrent overt FL(Case 1), and one with concurrent peripheral T
      cell lymphoma (PTCL),NOS (Case 2) in the same lymph node. Immunohistochemistry,
      polymerase chain reaction for B and T-cell clonality, and double-staining
      chromogenic in situ hybridization for BCL2 translocation were performed.In both
      cases, the in situ FL foci were characterized by strong expression of BCL2 and
      CD10 in the germinal center B cells of the affected follicles. Case 1 showed the
      concurrence of an overt B-cell FL with IgH@ rearrangement and expression of B
      cell markers, but not BCL2. Case 2 demonstrated the concurrence of a PTCL, NOS
      with TCRG@ rearrangement and expression of T-cell markers. In conclusion,the
      association of in situ FL with PTCL expands the spectrum of lymphoproliferations
      that may coexist with in situ FL and suggests that in situ FL may not behave like
      a simple precursor for overt FL.

PMID- 21956857
TI  - Use and costs of oral anticancer agents in the Netherlands in the period 2000
      2008.
AB  - PURPOSE: In recent years, the number of oral anticancer agents has increased
      substantially. Although these agents have quickly been incorporated in the
      treatment of a variety of malignancies, data on their incidence, prevalence and
      costs are lacking. The objective of the present study was to obtain insight into
      the use and the costs of oral anticancer agents (with Anatomical Therapeutic
      Chemical classification system (World Health Organisation) code L01) in the
      Netherlands between 2000 and 2008. METHODS: Incidence and prevalence were
      determined using community pharmacy dispensing records obtained from the PHARMO
      Record Linkage System database. The data of costs were provided by the Genees- en
      hulpmiddelen Informatie Project of the Dutch Health Care Insurance Board (CVZ,
      Diemen, The Netherlands). RESULTS: In the years 2000-2008, the use of oral
      anticancer agents has more than doubled from 64 to 140 users per 100 000
      inhabitants. The increase is mainly caused by the prescription of capecitabine
      for various indications. There was a 50-fold rise in costs on oral anticancer
      agents from ?2 m in 2000 to approximately ?100 m in 2008. The share in the costs
      of tyrosine kinase inhibitors (TKIs) in 2008 was 67% (?70 m) with the oldest TKI,
      imatinib, having a share of more than 50% within the group of TKIs. CONCLUSIONS:
      The increased use of oral anticancer agents is mainly due to the frequent
      prescription of capecitabine. The increased costs are caused by the registration
      of a variety of TKIs, in particular imatinib. The costs of new agents with an
      orphan drug status are very high as compared with those of capecitabine, a newer
      agent for which there are alternative treatment options.

PMID- 21956858
TI  - A convenient and general palladium-catalyzed carbonylative coupling for the
      synthesis of 2-arylbenzoxazinones.

PMID- 21956859
TI  - Uniaxially oriented peptide crystals for active optical waveguiding.

PMID- 21956860
TI  - Is universal, simple melting point prediction possible?
AB  - An investigation of the melting points of 520 organic 1:1 salts is presented with
      the aim of developing a universal, simple, physically well-founded prediction
      scheme. The general reliability and reproducibility of the recorded experimental
      data are discussed with respect to purity, phase behavior, disorder and thermal
      history of a given substance. Additionally, mistakes, systematic errors, or lack
      of conventions can lead to considerable differences in the experimental
      measurements. A rough error bar for the reproducibility of the melting points of
      organic salts of +/-5 to +/-15  degrees C can be assigned. With this restraint,
      we developed two simple, semiempirical, five- and nine-parameter schemes with
      easy-to-calculate quantities. With these, we could predict the melting
      temperature of a given organic salt in the temperature range of -25 to +300 
      degrees C with an average error of 33.5  degrees C and a relative error of 9.3%.
      All calculated quantities are assessed with the help of conventional DFT, COSMO
      and COSMO-RS calculations, and are currently implemented into the IL-Prop module
      of the upcoming version of COSMOtherm. These prediction schemes are suitable for
      high-throughput computational screening of substances in the context of "computer
      aided synthesis". Therefore, they are valuable tools to find a compound with a
      suitable melting point before its first synthesis.

PMID- 21956861
TI  - An efficient zinc-catalyzed dehydration of primary amides to nitriles.
AB  - In the present study, the zinc-catalyzed dehydration of a variety of amides with
      N-methyl-N-(trimethylsilyl)trifluoroacetamide (MSTFA) as a dehydration reagent
      into the corresponding nitriles has been examined in detail. With the
      straightforward and commercially available zinc(II)triflate as the precatalyst
      and MSTFA, an excellent system has been established to afford nitriles in
      excellent yields and chemoselectivities. After investigation of reaction
      conditions and the scope and limitations, several efforts were carried out to
      understand the reaction mechanism.

PMID- 21956862
TI  - Changes in triacylglycerol-accumulated fiber type, fiber type composition, and
      biogenesis in the mitochondria of the soleus muscle in obese rats.
AB  - Little is known about the effects of obesity on skeletal muscle consisting of
      approximately 80% type I (slow) fibers, such as that in the soleus muscle,
      although type I fibers have an enhanced capacity for mitochondrial respiration
      and fatty acid oxidation. We investigated the effects of obesity on the soleus
      muscle in the rat. Rats were fed a high-fat diet (protein:fat:carbohydrate =
      20:57:23; 508 kcal/100 g) or a control diet (protein:fat:carbohydrate = 20:10:70;
      366 kcal/100 g) for 10 weeks. We analyzed the accumulation of intramyocellular
      triacylglycerol (IMTG), fiber type composition, and the biogenesis and function
      of the mitochondria in the soleus muscle of the rat during 10 weeks of feeding,
      using histochemical and real-time polymerase chain reaction analyses. Obesity
      increased body weight and markedly elevated IMTG levels in type I, but not in
      type II, fibers of the soleus muscle throughout the feeding period. Obesity also
      inhibited the biogenesis and function in the mitochondria and altered the fiber
      type composition in the soleus muscle. The suppression of biogenesis and function
      in the mitochondria, and the alteration in the fiber type composition may be
      attributable to the marked IMTG accumulation in the soleus muscle of the rat.

PMID- 21956863
TI  - Analysis of the serine/threonine/tyrosine phosphoproteome of the pathogenic
      bacterium Listeria monocytogenes reveals phosphorylated proteins related to
      virulence.
AB  - Phosphorylation is the most common and widely studied post-translational protein
      modification in bacteria. It plays an important role in all kinds of cellular
      processes and controls key regulatory mechanisms, including virulence in certain
      pathogens. To gain insight into the role of protein phosphorylation in the
      pathogen Listeria monocytogenes, the serine (Ser), threonine (Thr) and tyrosine
      (Tyr) phosphoproteome of this bacterium was determined. We used the "gel free"
      proteomic approach with high accuracy mass spectrometry after enrichment of
      phosphopeptides. A total of 143 sites of phosphorylation were clearly identified,
      on 155 unique peptides of 112 phosphoproteins. The Ser/Thr/Tyr phosphorylation
      site distribution was 93:43:7. All identified phosphopeptides are
      monophosphorylated, except one and many identified phosphoproteins are related to
      virulence, translation, phosphoenolpyruvate:sugar phosphotransferase system,
      glycolysis and stress response. A description of these phosphoproteins is
      provided together with a comparison of the phosphosites in the L. monocytogenes
      proteins and in their homologues of other bacteria for which the phosphoproteome
      has been determined. Compared with the previous studies, we noticed a more
      extended conservation of the phosphorylation sites in glycolytic enzymes as well
      as ribosomal proteins.

PMID- 21956864
TI  - Tailored materials for high-performance MgB(2) wire.

PMID- 21956865
TI  - A reproducible method for damage-free site-specific preparation of atom probe
      tips from interfaces.
AB  - Atom probe tomography (APT) is a mass spectrometry method with atomic-scale
      spatial resolution that can be used for the investigation of a wide range of
      materials. The main limiting factor with respect to the type of problems that can
      be addressed is the small volume investigated and the randomness of common sample
      preparation methods. With existing site-specific specimen preparation methods it
      is still challenging to rapidly and reproducibly produce large numbers of
      successful samples from specifically selected grain boundaries or interfaces for
      systematic studies. A new method utilizing both focused ion beam (FIB) and
      transmission electron microscopy (TEM) is presented that can be used to
      reproducibly produce damage-free atom probe samples with features of interest at
      any desired orientation with an accuracy of better than 50 nm from samples that
      require very little prior preparation.

PMID- 21956866
TI  - The use of fluoride as a leaving group: SN2' displacement of a C-F bond on 3,3
      difluoropropenes with organolithium reagents to give direct access to
      monofluoroalkenes.

PMID- 21956867
TI  - The impact of paracetamol on selected biomarkers of the mollusc species Corbicula
      fluminea.
AB  - The Asian clam Corbicula fluminea is an invasive bivalve that has recently spread
      in Europe and currently represents a large portion of the aquatic biomass in
      specific areas. Because of the impacts that the species may have in invaded
      ecosystems, increased knowledge on the physiologic features of the species life
      cycle under different environmental scenarios (e.g., contamination events) is
      critical to understand the dynamics of the invasion and resulting ecosystem
      imbalance. The presence of pharmaceutical residues in the aquatic environment has
      recently received great attention since high levels of contamination have been
      found, not only in sewage treatment plant effluents, but also in open waters. The
      present article reports toxicological biochemical effects of paracetamol to
      Corbicula fluminea following short- and long-term exposures. Oxidative stress
      parameters were specially focused namely catalase (CAT), glutathione S
      transferases (GSTs), and glutathione reductase (GRed). The effect of tested
      substances on lipid peroxidation was also investigated. Paracetamol did not
      induce alterations on CAT activity, caused a significant decrease of GSTs
      activity following short- and long-term exposure (LOEC values of 532.78 mg L(-1)
      and 30.98 MUg L(-1) , respectively), and was responsible for a significant and
      dose-dependent decrease of GRed activity in short- and long-term exposures. These
      results indicate that exposure to paracetamol can provoke significant alterations
      on the cellular redox status of C. fluminea.

PMID- 21956868
TI  - Oxidative decarboxylation of benzilic acid by a biomimetic iron(II) complex:
      evidence for an iron(IV)-oxo-hydroxo oxidant from O2.

PMID- 21956869
TI  - Water-soluble prodrug of antimicrotubule agent plinabulin: effective strategy
      with click chemistry.

PMID- 21956870
TI  - mSmile is necessary for bronchial smooth muscle and alveolar myofibroblast
      development.
AB  - Disrupted lung alveolar myofibroblast and bronchial smooth muscle (BSM) cell
      development may lead to pulmonary disorders such as bronchopulmonary dysplasia.
      The molecular mechanisms that regulate BSM and alveolar myofibroblast development
      are not fully understood. Here we show that mSmile (murine Smile), a novel
      transmembrane protein with tetratricopeptide repeats, functions in lung alveolar
      myofibroblast and BSM cell development. mSmile mutant mice exhibit early neonatal
      lethality with few mice surviving up to 3 weeks. Mutant lungs display both airway
      branching morphogenesis defect during fetal lung development and alveolarization
      defect after birth. These defects are associated with reduced numbers of BSM
      cells in the peribronchial subepithelial region and clefts and myofibroblasts in
      alveolar septae. Expression of fibroblast growth factor-10 and its down stream
      target Bmp-4, which are important for BSM formation, is decreased. In vitro,
      mSmile mutant embryonic fibroblasts show reduced receptor activation and
      induction of myofibroblast formation in response to Transforming growth factor
      beta (Tgf-beta), indicating that mSmile may mediate myofibroblast development
      through modulation of Tgf-beta signaling. These studies identify mSmile as a
      novel gene specifying both the BSM and lung alveolar myofibroblast lineages,
      contributing to our understanding of the biological control of the development of
      these cells, and may provide insights into the aberrant smooth muscle and
      alveolar myofibroblast development that occur in pathological conditions.

PMID- 21956871
TI  - Confocal microscopy with double immunofluorescence staining reveals the
      functional transient receptor potential vanilloid subtype 1 expressed in
      myoepithelial cells of human submandibular glands.
AB  - Myoepithelial cells (MECs) mainly surround acini and intercalated ducts in the
      human salivary glands. The contraction of MECs provides the expulsive force to
      promote salivation. We previously found functional transient receptor potential
      vanilloid subtype 1 (TRPV1) was expressed in rabbit and human submandibular
      glands and increased saliva secretion. However, it was unknown whether TRPV1 was
      expressed in MECs of submandibular glands. In this study, we observed the
      immunoflourescence of TRPV1 was not only located in serous acini and ducts but
      also surround the basal layer of the acinus and intercalated ducts of human
      submandibular glands. Double immunofluorescence staining revealed colocalization
      of TRPV1 with calponin, vimentin, and alpha-smooth muscle actin, which indicated
      the myoepithelial expression of TRPV1. Treating submandibular gland tissues with
      capsaicin, an agonist of TRPV1, substantially increased the phosphorylation of
      the 20-kDa regulatory light-chain subunit of myosin (MLC(20) ), a crucial
      molecule for contraction of smooth muscle cells, in MECs. Pretreatment with
      capsazepine, a specific TRPV1 inhibitor, blocked capsaicin-induced MLC(20)
      phosphorylation. These results suggest that TRPV1 is expressed in MECs of the
      human submandibular gland and mediates myoepithelial contraction via a mechanism
      involving MLC(20) phosphorylation.

PMID- 21956872
TI  - Multiplexed immuno-precipitation with 1725 commercially available antibodies to
      cellular proteins.
AB  - Antibody array analysis of complex samples requires capture reagents with
      exceptional specificity. The frequency of antibodies with label-based detection
      may be as low as 5%. Here, however, we show that as many as 25% of commercially
      available antibodies are useful when biotinylated cellular proteins are
      fractionated by size exclusion chromatography (SEC) first. A microsphere
      multiplex with 1725 antibodies to cellular proteins was added to 24 SEC
      fractions, labelled with streptavidin and analyzed by flow cytometry (microsphere
      based affinity proteomics, MAP) The SEC-MAP approach resolved different targets
      captured by each antibody as reactivity peaks across the separation range of the
      SEC column (10-670kDa). Complex reactivity profiles demonstrated that most
      antibodies bound more than one target. However, specific binding was readily
      detected as reactivity peaks common for different antibodies to the same protein.
      We optimized sample preparation and found that amine-reactive biotin rarely
      inhibited antibody binding when the biotin to lysine ratio was kept below 1:1
      during labelling. Moreover, several epitopes that were inaccessible to antibodies
      in native proteins were unmasked after heat denaturation with 0.1% of SDS. The
      SEC-MAP format should allow researchers to build multiplexed assays with
      antibodies purchased for use in e.g. Western blotting.

PMID- 21956873
TI  - Hydroamination of alkynes with ammonia: unforeseen role of the gold(I) catalyst.

PMID- 21956874
TI  - Indene formation under single-collision conditions from the reaction of phenyl
      radicals with allene and methylacetylene--a crossed molecular beam and ab initio
      study.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are regarded as key intermediates in the
      molecular growth process that forms soot from incomplete fossil fuel combustion.
      Although heavily researched, the reaction mechanisms for PAH formation have only
      been investigated through bulk experiments; therefore, current models remain
      conjectural. We report the first observation of a directed synthesis of a PAH
      under single-collision conditions. By using a crossed-molecular-beam apparatus,
      phenyl radicals react with C(3)H(4) isomers, methylacetylene and allene, to form
      indene at collision energies of 45 kJ mol(-1). The reaction dynamics supported by
      theoretical calculations show that both isomers decay through the same collision
      complex, are indirect, have long lifetimes, and form indene in high yields.
      Through the use of deuterium-substituted reactants, we were able to identify the
      reaction pathway to indene.

PMID- 21956875
TI  - Mental health professionals' attitudes to partnership in medicine taking: a
      validation study of the Leeds Attitude to Concordance Scale II.
AB  - PURPOSE: To explore psychiatrists' attitudes toward concordance by validating the
      Leeds Attitude to Concordance Scale II (LATCon II) in a Spanish sample. METHODS:
      This was a cross-sectional survey. An opportunistic sample of 125 psychiatrist
      and 100 psychiatry registrars attending a national conference completed the
      LATCon II questionnaire and sociodemographic and professional data. The principal
      component analysis of the LATCon II items was performed. Associations with
      sociodemographic and mental health professional variables were calculated.
      RESULTS: Principal component analysis yielded three components labeled
      "communication/empathy," "shared control," and "eventual paternalistic style."
      Women obtained significantly lower scores than men on the second component.
      Mental health professional variables were not related to attitude to concordance.
      CONCLUSIONS: Psychiatrists show a favorable attitude to involve patients in a
      process of reciprocal communication, where patients' preferences, values, and
      expectations are considered, but they are more cautious in their attitude to
      sharing decisions with patients. There is scope for the different kinds of
      research in this area: studying sex-based differences in psychiatrists' attitudes
      to concordance and also exploring the gap in mental health care between patients'
      and professionals' views of shared decision making. Only in this way can the real
      partnership for shared decision making be fully understood.

PMID- 21956876
TI  - Mini-STAR as bail-out strategy for percutaneous coronary intervention of chronic
      total occlusion.
AB  - BACKGROUND: Although the advancement of the equipment and the presence of
      innovative techniques, percutaneous coronary intervention (PCI) for chronic total
      occlusion (CTO) continues to be affected by lower procedural success in
      comparison with non occluded vessel PCI. OBJECTIVE: We describe a new technique
      for the treatment of coronary CTO which utilizes a new generation of polymeric
      wires. METHODS AND RESULT: From March 2009 to June 2010 different strategies were
      adopted as "bail out" after an initial attempt failed in 117 consecutive CTO
      lesions. Among these, conventional strategies (CS) such as parallel wire, sub
      intimal tracking and re-entry (STAR), microchannel technique, intracoronary
      ultrasound guided revascularization and anchor balloon, were used in 75 cases
      (64.1%), while in the remaining a new technique, the "mini-STAR," was used
      (39.9%). Although no substantial differences were observed regarding the
      distribution of clinical features and angiographic lesions characteristics
      between the populations, mini-STAR was able to achieve a higher rate of
      procedural success in comparison with other CS (97.6% vs. 52%, P < 0.001) with
      lower contrast agent use (442 +/- 259 cm(3) vs. 561 +/- 243 cm(3), P = 0.01) and
      shorter procedural and fluoroscopy times (122 +/- 61 vs. 157 +/- 74 min, P =
      0.009 and 60 +/- 31 min vs. 75 +/- 38 min, P = 0.03, respectively). No
      differences were observed in term of peri-procedural complications such as
      procedural myocardial infarction, coronary perforations, and contrast-induced
      nephropathy between mini-STAR and CS. CONCLUSION: The mini-STAR technique is a
      promising strategy for the treatment of CTO lesions, achieving a high procedural
      success rate and low occurrence of procedural adverse events.

PMID- 21956881
TI  - Ruthenium-catalyzed isoquinolone synthesis through C-H activation using an
      oxidizing directing group.

PMID- 21956883
TI  - The proteomics of cancer stem cells: potential clinical applications for
      innovative research in oncology.
AB  - Cancer stem cells (CSCs) or tumour-maintaining cells are becoming an important
      new reality in oncology. The intriguing molecular pathophysiology of CSCs may
      justify some of the obscure pathogenetic, diagnostic, prognostic, and above all,
      therapeutic aspects of cancer and, eventually, lead to new solutions in oncology.
      CSC is a cell within the tumour that possesses the capacity to self-renew and, in
      doing so, gives rise to the heterogeneous lineages that comprise the tumour. The
      precise identification of this peculiar subpopulation of cancer cells, which has
      some intriguing similarities to normal stem cells, is becoming an important and
      urgent topic in oncology. In fact, some debated CSC markers have been already
      adopted by pharmacological research as targets of new and/or old anticancer
      drugs, showing an intriguing therapeutic index. These discussed identification
      markers include cell surface proteins, different activated signalling pathways,
      several molecules of the stem cell niche, various drug resistance mechanisms
      (ABCG2 and ALDH), telomerase, oncogenes and oncosuppressors (p16INK4 - Rb) and
      lastly, various microRNAs. In this new promising area of cancer research,
      proteomics, in general, and oncoproteomics, in particular, can and must play a
      significant role if the methodological approaches and the experimental protocols
      are correctly designed and interpreted.

PMID- 21956882
TI  - Direct arylation of 6-phenylpurine and 6-arylpurine nucleosides by ruthenium
      catalyzed C-H bond activation.

PMID- 21956885
TI  - Well-defined soluble P(3-)-containing rare-earth-metal compounds.

PMID- 21956884
TI  - Quantitative proteomics analysis of adsorbed plasma proteins classifies
      nanoparticles with different surface properties and size.
AB  - Nanoparticle biological activity, biocompatibility and fate can be directly
      affected by layers of readily adsorbed host proteins in biofluids. Here, we
      report a study on the interactions between human blood plasma proteins and
      nanoparticles with a controlled systematic variation of properties using (18)O
      labeling and LC-MS-based quantitative proteomics. We developed a novel protocol
      to both simplify isolation of nanoparticle bound proteins and improve
      reproducibility. LC-MS analysis identified and quantified 88 human plasma
      proteins associated with polystyrene nanoparticles consisting of three different
      surface chemistries and two sizes, as well as, for four different exposure times
      (for a total of 24 different samples). Quantitative comparison of relative
      protein abundances was achieved by spiking an (18)O-labeled "universal" reference
      into each individually processed unlabeled sample as an internal standard,
      enabling simultaneous application of both label-free and isotopic labeling
      quantification across the entire sample set. Clustering analysis of the
      quantitative proteomics data resulted in distinctive patterns that classified the
      nanoparticles based on their surface properties and size. In addition, temporal
      data indicated that the formation of the stable protein corona was at equilibrium
      within 5 min. The comprehensive quantitative proteomics results obtained in this
      study provide rich data for computational modeling and have potential
      implications towards predicting nanoparticle biocompatibility.

PMID- 21956886
TI  - Generation of a conditional null allele of Lbx1.
AB  - The homeobox gene Lbx1 not only plays critical roles in myogenesis and
      neurogenesis during embryonic development but is also expressed in activated
      satellite cells of adult mice. To address the potential postnatal functions of
      Lbx1, we generated conditional Lbx1-null mice using the Cre-loxP system. We
      generated a mouse in which Exon 2 of Lbx1 was floxed (Lbx1flox/flox), followed by
      cross-breeding between the Lbx1flox/flox mouse and either a transgenic mouse
      where a tamoxifen-inducible Cre-recombinase (Cre) was ubiquitously expressed, or
      a Myf5Cre mouse where Cre was inserted into the Myf5 locus. In both Lbx1-null
      mouse lines generated, Pax3-expressing limb muscle precursor cells were seriously
      reduced during embryonic development and eventually the limb extensor muscles
      were lost after birth. Since the conditional Lbx1-null mice generated were viable
      for a prolonged time, they will be useful in the investigation of Lbx1 function
      throughout the lifespan of the mouse.

PMID- 21956887
TI  - A dynamic mathematical model for monoclonal antibody N-linked glycosylation and
      nucleotide sugar donor transport within a maturing Golgi apparatus.
AB  - Monoclonal antibodies (mAbs) are one of the most important products of the
      biopharmaceutical industry. Their therapeutic efficacy depends on the post
      translational process of glycosylation, which is influenced by manufacturing
      process conditions. Herein, we present a dynamic mathematical model for mAb
      glycosylation that considers cisternal maturation by approximating the Golgi
      apparatus to a plug flow reactor and by including recycling of Golgi-resident
      proteins (glycosylation enzymes and transport proteins [TPs]). The glycosylation
      reaction rate expressions were derived based on the reported kinetic mechanisms
      for each enzyme, and transport of nucleotide sugar donors [NSDs] from the cytosol
      to the Golgi lumen was modeled to serve as a link between glycosylation and
      cellular metabolism. Optimization-based methodologies were developed for
      estimating unknown enzyme and TP concentration profile parameters. The resulting
      model is capable of reproducing glycosylation profiles of commercial mAbs. It can
      further reproduce the effect gene silencing of the FucT glycosylation enzyme and
      cytosolic NSD depletion have on the mAb oligosaccharide profile. All novel
      elements of our model are based on biological evidence and generate more accurate
      results than previous reports. We therefore believe that the improvements
      contribute to a more detailed representation of the N-linked glycosylation
      process. The overall results show the potential of our model toward evaluating
      cell engineering strategies that yield desired glycosylation profiles.
      Additionally, when coupled to cellular metabolism, this model could be used to
      assess the effect of process conditions on glycosylation and aid in the design,
      control, and optimization of biopharmaceutical manufacturing processes.

PMID- 21956889
TI  - Bis(azobenzene)-based photoswitchable, prochiral, Calpha-tetrasubstituted alpha
      amino acids for nanomaterials applications.

PMID- 21956888
TI  - Achieving secondary structural resolution in kinetic measurements of protein
      folding: a case study of the folding mechanism of Trp-cage.

PMID- 21956891
TI  - Metabolomic analysis of a synthetic metabolic switch in Streptomyces coelicolor
      A3(2).
AB  - The global analysis of metabolism by liquid chromatography coupled to mass
      spectrometry is often hampered by a large amount of biological and technical
      variability. Here, we introduce an experimental and analytical strategy that can
      produce robust metabolome profiles in the face of this challenge. By applying a
      new computational approach based on concordance analysis to an extremely large
      number of analytical replicates, we are able to show that the overexpression of
      an antisense non-coding RNA targeting glutamine synthetase I results in a major
      reorganization of the metabolism of Streptomyces coelicolor, the model species of
      antibiotic-producing bacteria. We identified 97 metabolites with statistically
      significant reproducible dynamic behavior across the time series. The observed
      metabolic changes are very rapid, specific and widespread across metabolism, but
      focus on the nitrogen assimilation pathways. Our results demonstrate the power of
      highly replicated experimental designs for the robust characterization of
      metabolite dynamics. The identified global rearrangement of metabolism suggests
      the usefulness of RNA interference as an efficient strategy to manipulate the
      physiology of bacteria with wider biotechnological applicability in
      microorganisms.

PMID- 21956890
TI  - A method for isolation and identification of urinary biomarkers in patients with
      diabetic nephropathy.
AB  - PURPOSE: The poor performance of current tests for predicting the onset,
      progression and treatment response of diabetic nephropathy has engendered a
      search for more sensitive and specific urinary biomarkers. Our goal was to
      develop a new method for protein biomarker discovery in urine from these
      patients. EXPERIMENTAL DESIGN: We analyzed urine from normal subjects and
      patients with early and advanced nephropathy. Proteins were separated using a
      novel analysis process including immunodepletion of high-abundance proteins
      followed by two-stage LC fractionation of low-abundance proteins. The proteins in
      the fractions were sequenced using MS/MS. RESULTS: Immunodepletion of selected
      high-abundance proteins followed by two-stage LC produced approximately 700
      fractions, each less complex and more amenable to analysis than the mixture and
      requiring minimal processing for MS identification. Comparison of fractions
      between normal and diabetic nephropathy subjects revealed several low-abundance
      proteins that reproducibly distinguished low glomerular filtration rate (GFR)
      from both high GFR diabetic and normal subjects, including uteroglobin, a protein
      previously associated with renal scarring. CONCLUSIONS AND CLINICAL RELEVANCE: We
      developed a novel method to identify low-abundance urinary proteins that enables
      the discovery of potential biomarkers to improve the diagnosis and management of
      patients with diabetic nephropathy.

PMID- 21956893
TI  - Fritz Haber: the damned scientist.

PMID- 21956892
TI  - Rho GTPases mediate the mechanosensitive lineage commitment of neural stem cells.
AB  - Adult neural stem cells (NSCs) play important roles in learning and memory and
      are negatively impacted by neurological disease. It is known that biochemical and
      genetic factors regulate self-renewal and differentiation, and it has recently
      been suggested that mechanical and solid-state cues, such as extracellular matrix
      (ECM) stiffness, can also regulate the functions of NSCs and other stem cell
      types. However, relatively little is known of the molecular mechanisms through
      which stem cells transduce mechanical inputs into fate decisions, the extent to
      which mechanical inputs instruct fate decisions versus select for or against
      lineage-committed blast populations, or the in vivo relevance of
      mechanotransductive signaling molecules in native stem cell niches. Here we
      demonstrate that ECM-derived mechanical signals act through Rho GTPases to
      activate the cellular contractility machinery in a key early window during
      differentiation to regulate NSC lineage commitment. Furthermore, culturing NSCs
      on increasingly stiff ECMs enhances RhoA and Cdc42 activation, increases NSC
      stiffness, and suppresses neurogenesis. Likewise, inhibiting RhoA and Cdc42 or
      downstream regulators of cellular contractility rescues NSCs from stiff matrix-
      and Rho GTPase-induced neurosuppression. Importantly, Rho GTPase expression and
      ECM stiffness do not alter proliferation or apoptosis rates indicating that an
      instructive rather than selective mechanism modulates lineage distributions.
      Finally, in the adult brain, RhoA activation in hippocampal progenitors
      suppresses neurogenesis, analogous to its effect in vitro. These results
      establish Rho GTPase-based mechanotransduction and cellular stiffness as
      biophysical regulators of NSC fate in vitro and RhoA as an important regulatory
      protein in the hippocampal stem cell niche.

PMID- 21956894
TI  - Assessing vaccine safety communication with healthcare providers in a large urban
      county.
AB  - PURPOSE: Vaccination is the primary public health tool for influenza control.
      Rapid assessment of the safety of any widely disseminated pandemic influenza
      vaccine is a public health priority. This study identifies practices, strengths,
      and weaknesses of vaccine-associated adverse event (AE) reporting to inform
      public health systems improvement. METHODS: A survey was developed with local and
      state health agencies' input. After pre-testing, the survey was distributed
      online and via mail to a random sample of King County, WA, healthcare
      professionals, composed of 60 commercial vaccinator employees and school health
      nurses, 500 physicians, and 300 pharmacists. RESULTS: The response rate was 36%.
      Results indicate that if an AE was suspected, 17% of respondents would not know
      how to report it, with 61% of respondents citing unclear definitions of a
      reportable AE as a barrier and 18% of respondents unaware of whose responsibility
      it is to report an AE. CONCLUSION: Healthcare professionals who provide
      immunizations need additional information on their role in vaccine safety and AE
      reporting. Strengthening both passive and active reporting systems can enhance
      surveillance efforts during real-time events, such as mass immunization during a
      pandemic and other large-scale emergency countermeasure distribution programs.

PMID- 21956895
TI  - Toward an unbiased evolutionary platform for unraveling Xenopus developmental
      gene networks.
AB  - The availability of both the Xenopus tropicalis genome and the soon to be
      released Xenopus laevis genome provides a solid foundation for Xenopus
      developmental biologists. The Xenopus community has presently amassed expression
      data for ~2,300 genes in the form of published images collected in the Xenbase,
      the principal Xenopus research database. A few of these genes have been examined
      in both X. tropicalis and X. laevis and the cross-species comparison has been
      proven invaluable for studying gene function. A recently published work has
      yielded developmental expression profiles for the majority of Xenopus genes
      across fourteen developmental stages spanning the blastula, gastrula, neurula,
      and the tail-bud. While this data was originally queried for global evolutionary
      and developmental principles, here we demonstrate its general use for gene-level
      analyses. In particular, we present the accessibility of this dataset through
      Xenbase and describe biases in the characterized genes in terms of sequence and
      expression conservation across the two species. We further indicate the advantage
      of examining coexpression for gene function discovery relating to developmental
      processes conserved across species. We suggest that the integration of additional
      large-scale datasets--comprising diverse functional data--into Xenbase promises
      to provide a strong foundation for researchers in elucidating biological
      processes including the gene regulatory programs encoding development.

PMID- 21956896
TI  - Atomic resolution analysis of silver ion-exchanged zeolite A.

PMID- 21956897
TI  - Solid-state structural transformations from 2D interdigitated layers to 3D
      interpenetrated structures.

PMID- 21956898
TI  - Brief report: phenotypic rescue of induced pluripotent stem cell-derived
      motoneurons of a spinal muscular atrophy patient.
AB  - Spinal muscular atrophy (SMA) is one of the most common autosomal recessive
      disorders in humans and is a common genetic cause of infant mortality. The
      disease is caused by loss of the survival of motoneuron (SMN) protein, resulting
      in the degeneration of alpha motoneurons in spinal cord and muscular atrophy in
      the limbs and trunk. One function of SMN involves RNA splicing. It is unclear why
      a deficiency in a housekeeping function such as RNA splicing causes profound
      effects only on motoneurons but not on other cell types. One difficulty in
      studying SMA is the scarcity of patient's samples. The discovery that somatic
      cells can be reprogrammed to become induced pluripotent stem cell (iPSCs) raises
      the intriguing possibility of modeling human diseases in vitro. We reported the
      establishment of five iPSC lines from the fibroblasts of a type 1 SMA patient.
      Neuronal cultures derived from these SMA iPSC lines exhibited a reduced capacity
      to form motoneurons and an abnormality in neurite outgrowth. Ectopic SMN
      expression in these iPSC lines restored normal motoneuron differentiation and
      rescued the phenotype of delayed neurite outgrowth. These results suggest that
      the observed abnormalities are indeed caused by SMN deficiency and not by iPSC
      clonal variability. Further characterization of the cellular and functional
      deficits in motoneurons derived from these iPSCs may accelerate the exploration
      of the underlying mechanisms of SMA pathogenesis.

PMID- 21956899
TI  - High nuclear RBM3 expression is associated with an improved prognosis in
      colorectal cancer.
AB  - PURPOSE: In this study, we investigated the prognostic impact of human RBM3
      expression in colorectal cancer using tissue microarray-based immunohistochemical
      analysis. EXPERIMENTAL DESIGN: One polyclonal antibody and four monoclonal anti
      RBM3 antibodies were generated and epitope mapped using two different methods.
      Bacterial display revealed five distinct epitopes for the polyclonal antibody,
      while the four mouse monoclonal antibodies were found to bind to three of the
      five epitopes. A peptide suspension bead array assay confirmed the five epitopes
      of the polyclonal antibody, while only one of the monoclonal antibodies could be
      mapped using this approach. Antibody specificity was confirmed by Western
      blotting and immunohistochemistry, including siRNA-mediated knock-down. Two of
      the antibodies (polyclonal and monoclonal) were subsequently used to analyze RBM3
      expression in tumor samples from two independent colorectal cancer cohorts, one
      consecutive cohort (n=270) and one prospectively collected cohort of patients
      with cancer of the sigmoid colon (n=305). RBM3-expression was detected, with high
      correlation between both antibodies (R=0.81, p<0.001). RESULTS: In both cohorts,
      tumors with high nuclear RBM3 staining had significantly prolonged the overall
      survival. This was also confirmed in multivariate analysis, adjusted for
      established prognostic factors. CONCLUSION AND CLINICAL RELEVANCE: These data
      demonstrate that high tumor-specific nuclear expression of RBM3 is an independent
      predictor of good prognosis in colorectal cancer.

PMID- 21956900
TI  - Modeling of an aerobic biofilm reactor with double-limiting substrate kinetics:
      bifurcational and dynamical analysis.
AB  - A mathematical model of an aerobic biofilm reactor is presented to investigate
      the bifurcational patterns and the dynamical behavior of the reactor as a
      function of different key operating parameters. Suspended cells and biofilm are
      assumed to grow according to double limiting kinetics with phenol inhibition
      (carbon source) and oxygen limitation. The model presented by Russo et al. is
      extended to embody key features of the phenomenology of the granular-supported
      biofilm: biofilm growth and detachment, gas-liquid oxygen transport, phenol, and
      oxygen uptake by both suspended and immobilized cells, and substrate diffusion
      into the biofilm. Steady-state conditions and stability, and local dynamic
      behavior have been characterized. The multiplicity of steady states and their
      stability depend on key operating parameter values (dilution rate, gas-liquid
      mass transfer coefficient, biofilm detachment rate, and inlet substrate
      concentration). Small changes in the operating conditions may be coupled with a
      drastic change of the steady-state scenario with transcritical and saddle-node
      bifurcations. The relevance of concentration profiles establishing within the
      biofilm is also addressed. When the oxygen level in the liquid phase is <10% of
      the saturation level, the biofilm undergoes oxygen starvation and the active
      biofilm fraction becomes independent of the dilution rate. (c) 2011 American
      Institute of Chemical Engineers Biotechnol. Prog., 2011.

PMID- 21956901
TI  - Copper(I)-catalyzed deacetylenative coupling of propargylic amines: an efficient
      synthesis of symmetric 1,4-diamino-2-butynes.

PMID- 21956902
TI  - 'Posttranscriptional': to life scientists, no longer a postscript.

PMID- 21956903
TI  - Long noncoding RNAs in mammalian cells: what, where, and why?
AB  - Not all long, polyadenylated cellular RNAs encode polypeptides. In recent years,
      it has become apparent that a number of organisms express abundant amounts of
      transcripts that lack open reading frames or that are retained in the nucleus.
      Rather than accumulating silently in the cell, we now know that many of these
      long noncoding RNAs (lncRNAs) play important roles in nuclear architecture or in
      the regulation of gene expression. Here, we discuss some recent progress in our
      understanding of the functions of a number of important lncRNAs in mammalian
      cells.

PMID- 21956904
TI  - Plant viruses versus RNAi: simple pathogens reveal complex insights on plant
      antimicrobial defense.
AB  - RNA interference (RNAi) and related processes serve as a nucleic-acid-mediated
      surveillance system conserved in almost all eukaryotic organisms. This
      surveillance system detects various forms of double-stranded RNA (dsRNA) in cells
      and initiates a cascade of events that degrades dsRNAs into small interfering
      RNAs (siRNAs) or microRNAs (miRNAs). These small RNAs in turn serve as sequence
      specific guides to interfere with the function of other nucleic acids through
      degradation or translational repression of homologous RNAs, or modification of
      homologous genome segments. One of the major roles of RNAi in plants and
      invertebrates is antiviral defense. Conversely, viruses have also evolved to
      encode suppressors of RNAi (VSRs), which disrupt RNAi at various steps. Research
      activities focusing on the relationship between plant viruses and RNAi have been
      essential to our current understanding of RNAi mechanisms.

PMID- 21956905
TI  - Posttranscriptional control and the role of RNA-binding proteins in gene
      regulation in trypanosomatid protozoan parasites.
AB  - Trypanosomatids are unicellular eukaryotes responsible for severe diseases in
      humans. They exhibit a number of remarkable biological phenomena, especially at
      the RNA level. During their life cycles, they alternate between a mammalian host
      and an insect vector and undergo profound biochemical and morphological
      transformations in order to adapt to the different environments they find within
      one or the other host species. These changes are orchestrated by specific gene
      expression programs. In contrast to other organisms, trypanosomatids do not
      regulate RNA polymerase II-dependent transcription initiation. Evidence so far
      indicates that the main control points in gene expression are mRNA degradation
      and translation. Recent studies have shown that RNA-binding proteins (RBPs) play
      a critical role in the developmental regulation of mRNA and protein abundance.
      RBPs seem to bind to specific subsets of mRNAs encoding functionally related
      proteins. These ribonucleoprotein complexes may represent posttranscriptional
      operons or regulons that are able to control the fate of multiple mRNAs
      simultaneously. We suggest that trypanosomatids transduce environmental signals
      into mRNA and protein abundance through posttranslational modification of RBPs.

PMID- 21956906
TI  - Viruses and the cellular RNA decay machinery.
AB  - The ability to control cellular and viral gene expression, either globally or
      selectively, is central to a successful viral infection, and it is also crucial
      for the host to respond and eradicate pathogens. In eukaryotes, regulation of
      message stability contributes significantly to the control of gene expression and
      plays a prominent role in the normal physiology of a cell as well as in its
      response to environmental and pathogenic stresses. Not surprisingly, emerging
      evidence indicates that there are significant interactions between the eukaryotic
      RNA turnover machinery and a wide variety of viruses. Interestingly, in many
      cases viruses have evolved mechanisms not only to evade eradication by these
      pathways, but also to manipulate them for enhanced viral replication and gene
      expression. Given our incomplete understanding of how many of these pathways are
      normally regulated, viruses should be powerful tools to help deconstruct the
      complex networks and events governing eukaryotic RNA stability.

PMID- 21956908
TI  - RNase MRP and disease.
AB  - The human RNase MRP complex consists of a catalytic RNA and several protein
      components. RNase MRP is a ubiquitously expressed eukaryotic endoribonuclease
      that cleaves various RNAs, including ribosomal, messenger, and mitochondrial
      RNAs, in a highly specific fashion. In several autoimmune diseases autoantibodies
      targeting RNase MRP have been found. These so-called anti-Th/To autoantibodies,
      which most frequently can be detected in the sera of scleroderma patients, are
      directed to several protein components of the RNase MRP and the evolutionarily
      related RNase P complex. It is not yet known whether the anti-Th/To immune
      response is an epiphenomenon or whether these autoantibodies play a role in the
      pathophysiology of the disease. The gene encoding the RNase MRP RNA was the first
      nuclear non-coding RNA gene demonstrated to be associated with a genetic disease.
      Mutations in this gene are causing the highly pleiotropic disease cartilage-hair
      hypoplasia (CHH). CHH patients are characterized by a short stature, hypoplastic
      hair, and short limbs. In addition, they show a predisposition to lymphomas and
      other cancers and suffer from defective T-cell immunity. Since the identification
      of the first CHH-associated mutations in 2001, many distinct mutations have been
      found in different patients. These mutations either affect the structure of the
      RNase MRP RNA or are located in the promoter region and reduce the expression
      levels. In this review article we will, after describing the biochemical aspects
      of RNase MRP, discuss the targeting of RNase MRP in autoimmunity and the role of
      mutations in the RNase MRP RNA gene in CHH.

PMID- 21956909
TI  - Biogenesis and function of endogenous and exogenous siRNAs.
AB  - RNA interference (RNAi) is a sequence-specific gene silencing, or 'knockdown',
      mechanism facilitated by short duplex strands of RNA with sequence
      complementarity to target mRNAs. RNAi has many different forms, including
      posttranscriptional gene silencing (PTGS), and transcriptional gene silencing
      (TGS). Here, we review the biogenesis and function of an endogenous set of small
      RNA gene regulators, called microRNAs, as well as the mechanism of exogenously
      delivered small interfering RNAs. The potential applications of RNAi-based
      therapeutics are also highlighted.

PMID- 21956910
TI  - No-go decay: a quality control mechanism for RNA in translation.
AB  - Eukaryotic cells have evolved multiple quality control mechanisms that recognize
      and eliminate defective mRNA during the process of translation. One mechanism,
      referred to as No-go decay (NGD), targets mRNAs with elongation stalls for
      degradation initiated by endonucleolytic cleavage in the vicinity of the stalled
      ribosome. NGD is promoted by the evolutionarily conserved Dom34 and Hbs1
      proteins, which are related to the translation termination factors eRF1 and eRF3,
      respectively. NGD is likely to occur by Dom34/Hbs1 interacting with the A site in
      the ribosome leading to release of the peptide or peptidyl-tRNA. The process of
      NGD and/or the function of Dom34/Hbs1 appear to be important in several different
      biological contexts.

PMID- 21956907
TI  - Inflammation: cytokines and RNA-based regulation.
AB  - The outcome of an inflammatory response depends upon the coordinated regulation
      of a variety of both pro-inflammatory and anti-inflammatory cytokines and other
      proteins. Regulation of these inflammation mediators can occur at multiple
      levels, including transcription, mRNA translation, post-translational
      modifications, and mRNA degradation. Post-transcriptional regulation has been
      shown to play an important role in controlling the expression of these mediators,
      allowing for normal initiation and resolution of the inflammatory response. Many
      inflammatory mediators have unstable mRNAs due, in part, to the presence of AU
      rich elements in their 3'-untranslated regions. Increasing numbers of RNA-binding
      proteins have been identified that can bind to these AU-rich elements and then
      regulate the stability and/or translation of the mRNA. This review summarizes
      current knowledge about the role of several RNA-binding proteins that act through
      AU-rich elements to post-transcriptionally regulate the biosynthesis of proteins
      involved in inflammation.

PMID- 21956911
TI  - Polyadenylation and beyond: emerging roles for noncanonical poly(A) polymerases.
AB  - The addition of nontemplated nucleotides, particularly adenylyl and uridylyl
      residues, to the 3' ends of RNA substrates has been the focus of much attention
      in recent years, and these studies have generated some intriguing surprises. In
      addition to the well-known canonical poly(A) polymerase (PAP) that polyadenylates
      mRNAs prior to export from the nucleus to the cytoplasm, a separate class of
      noncanonical poly(A) polymerases has emerged over the past decade. Studies on
      various organisms have led to the realization that these noncanonical PAPs, which
      are conserved from yeast to mammals, play crucial and diverse roles in the
      regulation of gene expression. Here we review the current knowledge of these
      enzymes, with an emphasis on the human proteins, and highlight recent discoveries
      that have implications far beyond the understanding of RNA metabolism itself.

PMID- 21956913
TI  - Repeat expansion diseases: when a good RNA turns bad.
AB  - An increasing number of dominantly inherited diseases have now been linked with
      expansion of short repeats within specific genes. Although some of these
      expansions affect protein function or result in haploinsufficiency, a significant
      portion cause pathogenesis through production of toxic RNA molecules that alter
      cellular metabolism. In this review, we examine the criteria that influence
      toxicity of these mutant RNAs and discuss new developments in therapeutic
      approaches.

PMID- 21956912
TI  - Enzymology of RNA cap synthesis.
AB  - The 5' guanine-N7 methyl cap is unique to cellular and viral messenger RNA (mRNA)
      and is the first co-transcriptional modification of mRNA. The mRNA cap plays a
      pivotal role in mRNA biogenesis and stability, and is essential for efficient
      splicing, mRNA export, and translation. Capping occurs by a series of three
      enzymatic reactions that results in formation of N7-methyl guanosine linked
      through a 5'-5' inverted triphosphate bridge to the first nucleotide of a nascent
      transcript. Capping of cellular mRNA occurs co-transcriptionally and in vivo
      requires that the capping apparatus be physically associated with the RNA
      polymerase II elongation complex. Certain capped mRNAs undergo further
      methylation to generate distinct cap structures. Although mRNA capping is
      conserved among viruses and eukaryotes, some viruses have adopted strategies for
      capping mRNA that are distinct from the cellular mRNA capping pathway.

PMID- 21956914
TI  - Connections between 3'-end processing and DNA damage response.
AB  - The cellular DNA damage response (DDR) involves changes in the functional and
      structural properties of a number of nuclear proteins, resulting in a coordinated
      control of gene expression and DNA repair. This response includes functional
      interactions of the DNA repair, transcription, and RNA processing machineries.
      Following DNA damage, cellular levels of polyadenylated transcripts are
      transiently decreased and normal recovery depends on transcription-coupled repair
      (TCR). In addition, DNA damage has gene-specific effects regulating the mRNA
      levels of factors involved in the DDR itself at different times after the damage.
      The 3'-end processing machinery, which is important in the regulation of mRNA
      stability, is involved in these general and gene-specific responses to DNA
      damage. The role of 3'-end processing in DDR supports the idea that the steady
      state levels of different mRNAs change upon DNA-damaging conditions as a result
      of regulation of not only their biosynthesis but also their turnover. Here, we
      review the mechanistic connections between 3'-end processing and DDR, and discuss
      the implications of deregulation of this important step of mRNA maturation in the
      cellular recovery after DNA-damaging treatment. The relevance of these functional
      connections is illustrated by the increasing number of reports on this relatively
      unexplored field.

PMID- 21956915
TI  - Statin usage and all-cause and disease-specific mortality in a nationwide study.
AB  - CONTEXT: The consumption of statins (HMG-CoA reductase inhibitors) in most
      Western countries has increased to the extent that it may affect all-cause and
      disease-specific mortality. OBJECTIVE: To analyze the association of statin use
      with all-cause and disease-specific mortality utilizing nationwide databases in a
      record linkage study in Finland. METHODS: The study population included all
      statin users in Finland who had purchased at least one prescription between 1997
      and 2005. A control population matched for age, sex, and place of residence and
      without statin usage was selected. The study population consisted of 336, 618
      pairs of individuals, and the mean length of follow-up was 4.4 years. All-cause
      mortality and mortality caused by coronary heart disease (CHD), stroke, other
      circulatory causes, cancer, unnatural causes, and suicide were analyzed.
      Persistence to treatment was calculated by varying adherence criteria between 20
      and 80%. RESULTS: We observed association between all-cause, non-CHD and CHD and
      treatment with statins in statin user group. For CHD mortality, we observed a
      relationship between the persistence to statin treatment and a decreasing CHD
      mortality. For each 10% increase in adherence criteria, a 5% (2-8%) decrease in
      CHD mortality was observed within the range of 20% (RR 0.81, 95%CI 0.32-2.02) to
      80% (RR 0.54, 95%CI 0.46-0.64). CONCLUSION: In this nationwide study, long-term
      use of statins is associated with the reduction in CHD mortality.

PMID- 21956920
TI  - Re: Ketoacidosis with unexpected serum isopropyl alcohol.

PMID- 21956919
TI  - Ketoacidosis with unexpected serum isopropyl alcohol.

PMID- 21956921
TI  - Re: Ketoacidosis with unexpected serum isopropyl alcohol.

PMID- 21956922
TI  - Molecular alterations during progression of prostate cancer to androgen
      independence.
AB  - BACKGROUND: Prostate cancer is the most commonly diagnosed cancer among men in
      North America and is a leading cause of death. Standard treatments include
      androgen deprivation therapy, which leads to improved clinical outcomes. However,
      over time, most tumors become androgen independent and no longer respond to
      hormonal therapies. Several mechanisms have been implicated in the progression of
      prostate cancer to androgen independence. CONTENT: Most tumors that have become
      androgen independent still rely on androgen receptor (AR) signaling. Mechanisms
      that enhance AR signaling in androgen-depleted conditions include: AR gene
      amplification, AR mutations, changes in the balance of AR cofactors, increases in
      steroidogenic precursors, and activation via "outlaw" pathways. Along with AR
      signaling, various other AR-independent "bypass" pathways have been shown to
      operate aberrantly during androgen independence. Changes in the epigenetic
      signatures and microRNA concentrations have also been implicated in the
      development of androgen-independent prostate cancer. SUMMARY: Understanding of
      the molecular mechanisms that lead to the development of androgen-independent
      prostate cancer will allow for improved therapeutic strategies that target key
      pathways and molecules that are essential for these cells to survive.

PMID- 21956923
TI  - What is your guess? Which count is correct?

PMID- 21956926
TI  - Fiber-based hybrid nanogenerators for/as self-powered systems in biological
      liquid.

PMID- 21956927
TI  - Changes in glycosphingolipid composition during differentiation of human
      embryonic stem cells to ectodermal or endodermal lineages.
AB  - Glycosphingolipids (GSLs) are ubiquitous components of cell membranes that can
      act as mediators of cell adhesion and signal transduction and can possibly be
      used as cell type-specific markers. Our previous study indicated that there was a
      striking switch in the core structures of GSLs during differentiation of human
      embryonic stem cells (hESCs) into embryoid body (EB), suggesting a close
      association of GSLs with cell differentiation. In this study, to further clarify
      if alterations in GSL patterns are correlated with lineage-specific
      differentiation of hESCs, we analyzed changes in GSLs as hESCs were
      differentiated into neural progenitors or endodermal cells by matrix-assisted
      laser desorption ionization mass spectrometry (MALDI-MS) and tandem mass
      spectrometry (MS/MS) analyses. During hESC differentiation into neural progenitor
      cells, we found that the core structures of GSLs switched from globo- and lacto-
      to mostly ganglio-series dominated by GD3. On the other hand, when hESCs were
      differentiated into endodermal cells, patterns of GSLs totally differed from
      those observed in EB outgrowth and neural progenitors. The most prominent GSL
      identified by the MALDI-MS and MS/MS analysis was Gb(4) Ceramide, with no
      appreciable amount of stage-specific embryonic antigens 3 or 4, or GD3, in
      endodermal cells. These changes in GSL profiling were accompanied by alterations
      in the biosynthetic pathways of expressions of key glycosyltransferases. Our
      findings suggest that changes in GSLs are closely associated with lineage
      specificity and differentiation of hESCs.

PMID- 21956928
TI  - Humoral immune responses to Plasmodium falciparum among HIV-1-infected Kenyan
      adults.
AB  - INTRODUCTION: Humoral immune responses play a pivotal role in naturally acquired
      immunity to malaria. Understanding which humoral responses are impaired among
      individuals at higher risk for malaria may improve our understanding of malaria
      immune control and contribute to vaccine development. METHODS: We compared
      humoral responses with 483 Plasmodium falciparum antigens between adults in,
      Kisumu (high, year-long malaria transmission leading to partial immunity), and
      adults in Kisii (low, seasonal malaria transmission). Then within each site, we
      compared malaria-specific humoral responses between those at higher risk for
      malaria (CD4(+) <=500) and those at lower risk for malaria (CD4(+) >500). A
      protein microarray chip containing 483 P. falciparum antigens and 71 HIV antigens
      was used. Benjamini-Hochberg adjustments were made to control for multiple
      comparisons. RESULTS: Fifty-seven antigens including CSP, MSP1, LSA1 and AMA1
      were identified as significantly more reactive in Kisumu than in Kisii. Ten of
      these antigens had been identified as protective in an earlier study. CD4(+) T
      cell count did not significantly impact humoral responses. CONCLUSION: Protein
      microarrays are a useful method to screen multiple humoral responses
      simultaneously. This study provides useful clues for potential vaccine
      candidates. Modest decreases in CD4 counts may not significantly impact malaria
      specific humoral immunity.

PMID- 21956929
TI  - Intrinsic curvature: a marker of millimeter-scale tangential cortico-cortical
      connectivity?
AB  - In this paper, we draw a link between cortical intrinsic curvature and the
      distributions of tangential connection lengths. We suggest that differential
      rates of surface expansion not only lead to intrinsic curvature of the cortical
      sheet, but also to differential inter-neuronal spacing. We propose that there
      follows a consequential change in the profile of neuronal connections:
      specifically an enhancement of the tendency towards proportionately more short
      connections. Thus, the degree of cortical intrinsic curvature may have
      implications for short-range connectivity.

PMID- 21956930
TI  - Responsive neuromodulators based on artificial neural networks used to control
      seizure-like events in a computational model of epilepsy.
AB  - Deep brain stimulation (DBS) has been noted for its potential to suppress
      epileptic seizures. To date, DBS has achieved mixed results as a therapeutic
      approach to seizure control. Using a computational model, we demonstrate that
      high-complexity, biologically-inspired responsive neuromodulation is superior to
      periodic forms of neuromodulation (responsive and non-responsive) such as those
      implemented in DBS, as well as neuromodulation using random and random repetitive
      interval stimulation. We configured radial basis function (RBF) networks to
      generate outputs modeling interictal time series recorded from rodent hippocampal
      slices that were perfused with low Mg2+/high K+ solution. We then compared the
      performance of RBF-based interictal modulation, periodic biphasic-pulse
      modulation, random modulation and random repetitive modulation on a cognitive
      rhythm generator (CRG) model of spontaneous seizure-like events (SLEs), testing
      efficacy of SLE control. A statistically significant improvement in SLE
      mitigation for the RBF interictal modulation case versus the periodic and random
      cases was observed, suggesting that the use of biologically-inspired
      neuromodulators may achieve better results for the purpose of electrical control
      of seizures in a clinical setting.

PMID- 21956931
TI  - Adaptive cerebellar spiking model embedded in the control loop: context switching
      and robustness against noise.
AB  - This work evaluates the capability of a spiking cerebellar model embedded in
      different loop architectures (recurrent, forward, and forward&recurrent) to
      control a robotic arm (three degrees of freedom) using a biologically-inspired
      approach. The implemented spiking network relies on synaptic plasticity (long
      term potentiation and long-term depression) to adapt and cope with perturbations
      in the manipulation scenario: changes in dynamics and kinematics of the simulated
      robot. Furthermore, the effect of several degrees of noise in the cerebellar
      input pathway (mossy fibers) was assessed depending on the employed control
      architecture. The implemented cerebellar model managed to adapt in the three
      control architectures to different dynamics and kinematics providing corrective
      actions for more accurate movements. According to the obtained results, coupling
      both control architectures (forward&recurrent) provides benefits of the two of
      them and leads to a higher robustness against noise.

PMID- 21956932
TI  - Automatic detection of epileptic EEG signals using higher order cumulant
      features.
AB  - The unpredictability of the occurrence of epileptic seizures makes it difficult
      to detect and treat this condition effectively. An automatic system that
      characterizes epileptic activities in EEG signals would allow patients or the
      people near them to take appropriate precautions, would allow clinicians to
      better manage the condition, and could provide more insight into these phenomena
      thereby revealing important clinical information. Various methods have been
      proposed to detect epileptic activity in EEG recordings. Because of the nonlinear
      and dynamic nature of EEG signals, the use of nonlinear Higher Order Spectra
      (HOS) features is a seemingly promising approach. This paper presents the
      methodology employed to extract HOS features (specifically, cumulants) from
      normal, interictal, and epileptic EEG segments and to use significant features in
      classifiers for the detection of these three classes. In this work, 300 sets of
      EEG data belonging to the three classes were used for feature extraction and
      classifier development and evaluation. The results show that the HOS based
      measures have unique ranges for the different classes with high confidence level
      (p-value < 0.0001). On evaluating several classifiers with the significant
      features, it was observed that the Support Vector Machine (SVM) presented a high
      detection accuracy of 98.5% thereby establishing the possibility of effective EEG
      segment classification using the proposed technique.

PMID- 21956933
TI  - Excitement and synchronization of small-world neuronal networks with short-term
      synaptic plasticity.
AB  - Excitement and synchronization of electrically and chemically coupled Newman
      Watts (NW) small-world neuronal networks with a short-term synaptic plasticity
      described by a modified Oja learning rule are investigated. For each type of
      neuronal network, the variation properties of synaptic weights are examined
      first. Then the effects of the learning rate, the coupling strength and the
      shortcut-adding probability on excitement and synchronization of the neuronal
      network are studied. It is shown that the synaptic learning suppresses the over
      excitement, helps synchronization for the electrically coupled network but
      impairs synchronization for the chemically coupled one. Both the introduction of
      shortcuts and the increase of the coupling strength improve synchronization and
      they are helpful in increasing the excitement for the chemically coupled network,
      but have little effect on the excitement of the electrically coupled one.

PMID- 21956934
TI  - A Lempel-Ziv complexity-based neural network pruning algorithm.
AB  - This paper presents a pruning method for artificial neural networks (ANNs) based
      on the 'Lempel-Ziv complexity' (LZC) measure. We call this method the 'silent
      pruning algorithm' (SPA). The term 'silent' is used in the sense that SPA prunes
      ANNs without causing much disturbance during the network training. SPA prunes
      hidden units during the training process according to their ranks computed from
      LZC. LZC extracts the number of unique patterns in a time sequence obtained from
      the output of a hidden unit and a smaller value of LZC indicates higher
      redundancy of a hidden unit. SPA has a great resemblance to biological brains
      since it encourages higher complexity during the training process. SPA is similar
      to, yet different from, existing pruning algorithms. The algorithm has been
      tested on a number of challenging benchmark problems in machine learning,
      including cancer, diabetes, heart, card, iris, glass, thyroid, and hepatitis
      problems. We compared SPA with other pruning algorithms and we found that SPA is
      better than the 'random deletion algorithm' (RDA) which prunes hidden units
      randomly. Our experimental results show that SPA can simplify ANNs with good
      generalization ability.

PMID- 21956935
TI  - Strain-promoted copper-free "click" chemistry for 18F radiolabeling of bombesin.

PMID- 21956936
TI  - Viroids: self-replicating, mobile, and fast-evolving noncoding regulatory RNAs.
AB  - Viroids are small, circular, and noncoding RNAs that infect plants. They
      replicate in the nucleus or chloroplast and then traffic from cell to cell and
      from organ to organ to establish systemic infection. Viroids achieve nearly all
      of the biological functions by directly interacting with host cellular factors.
      Viroid replication, together with replication of human hepatitis delta virus,
      demonstrates the biological novelty and significance of RNA-dependent RNA
      polymerase activities of DNA-dependent RNA polymerases. Viroid systemic infection
      uncovers a new biological principle--the role of three-dimensional RNA structural
      motifs mediating RNA trafficking between specific cells. Viroid diseases are
      virtually the consequences of host gene regulation by noncoding RNAs. A viroid
      RNA has the highest in vivo mutation rate among all known nucleic acid replicons.
      The host range of many viroids is expanding, essentially as a result of
      continuing and fast evolution of noncoding sequences/structures to gain new
      biological functions. Here, I discuss recent progress in these areas, emphasizing
      the broad significance of viroid research to the discovery of fundamental
      biological principles.

PMID- 21956937
TI  - DNA rearrangements directed by non-coding RNAs in ciliates.
AB  - Extensive programmed rearrangement of DNA, including DNA elimination, chromosome
      fragmentation, and DNA unscrambling, takes place in the newly developed
      macronucleus during the sexual reproduction of ciliated protozoa. Recent studies
      have revealed that two distant classes of ciliates use distinct types of non
      coding RNAs to regulate such DNA rearrangement events. DNA elimination in
      Tetrahymena is regulated by small non-coding RNAs that are produced and utilized
      in an RNA interference (RNAi)-related process. It has been proposed that the
      small RNAs produced from the micronuclear genome are used to identify eliminated
      DNA sequences by whole-genome comparison between the parental macronucleus and
      the micronucleus. In contrast, DNA unscrambling in Oxytricha is guided by long
      non-coding RNAs that are produced from the parental macronuclear genome. These
      long RNAs are proposed to act as templates for the direct unscrambling events
      that occur in the developing macronucleus. Both cases provide useful examples to
      study epigenetic chromatin regulation by non-coding RNAs.

PMID- 21956938
TI  - Dynamics and kinetics of nucleo-cytoplasmic mRNA export.
AB  - Activation of the gene expression pathway in eukaryotic cells results in the
      nuclear transcription of mRNA molecules, many of which are destined for
      translation into protein by cytoplasmic ribosomes. mRNA transcripts are exported
      from the nucleus to the cytoplasm via passage through nuclear pore complexes
      (NPCs), ~125 MDa supramolecular complexes set in the double-membraned nuclear
      envelope. Understanding the kinetics of mRNA translocation, from the point of
      transcription through export, localization, translation, and degradation, is of
      fundamental interest since gene expression is regulated at all the different
      levels of this pathway. In this review, we delineate the steps taken by an mRNA
      molecule in transit to the nuclear envelope and during mRNA export, with specific
      focus on the dynamic aspects of nucleo-cytoplasmic mRNA transport as revealed by
      electron microscopy and live-cell imaging.

PMID- 21956939
TI  - Viral tRNAs and tRNA-like structures.
AB  - Viruses commonly exploit or modify some aspect of tRNA biology. Large DNA
      viruses, especially bacteriophages, phycodnaviruses, and mimiviruses, produce
      their own tRNAs, apparently to adjust translational capacity during infection.
      Retroviruses recruit specific host tRNAs for use in priming the reverse
      transcription of their genome. Certain positive-strand RNA plant viral genomes
      possess 3'-tRNA-like structures (TLSs) that are built quite differently from
      authentic tRNAs, and yet efficiently recapitulate several properties of tRNAs.
      The structures and roles of these TLSs are discussed, emphasizing the variety in
      both structure and function.

PMID- 21956940
TI  - The nucleolus: structure/function relationship in RNA metabolism.
AB  - The nucleolus is the ribosome factory of the cells. This is the nuclear domain
      where ribosomal RNAs are synthesized, processed, and assembled with ribosomal
      proteins. Here we describe the classical tripartite organization of the nucleolus
      in mammals, reflecting ribosomal gene transcription and pre-ribosomal RNA (pre
      rRNA) processing efficiency: fibrillar center, dense fibrillar component, and
      granular component. We review the nucleolar organization across evolution from
      the bipartite organization in yeast to the tripartite organization in humans. We
      discuss the basic principles of nucleolar assembly and nucleolar
      structure/function relationship in RNA metabolism. The control of nucleolar
      assembly is presented as well as the role of pre-existing machineries and pre
      rRNAs inherited from the previous cell cycle. In addition, nucleoli carry many
      essential extra ribosomal functions and are closely linked to cellular
      homeostasis and human health. The last part of this review presents recent
      advances in nucleolar dysfunctions in human pathology such as cancer and virus
      infections that modify the nucleolar organization.

PMID- 21956941
TI  - Networks controlling mRNA decay in the immune system.
AB  - The active control of mRNA degradation has emerged as a key regulatory mechanism
      required for proper gene expression in the immune system. An adenosine/uridine
      (AU)-rich element (ARE) is at the heart of a first regulatory system that
      promotes the rapid degradation of a multitude of cytokine and chemokine mRNAs.
      AREs serve as binding sites for a number of regulatory proteins that either
      destabilize or stabilize the mRNA. Several kinase pathways regulate the activity
      of ARE-binding proteins and thereby coordinate the expression of their target
      mRNAs. Small regulatory micro (mi)-RNAs represent a second system that enhances
      the degradation of several mRNAs encoding important components of signal
      transduction cascades that are activated during adaptive and innate immune
      responses. Specific miRNAs are important for the differentiation of T helper
      cells, class switch recombination in B cells, and the maturation of dendritic
      cells. Excitement in this area of research is fueled by the discovery of novel
      RNA elements and regulatory proteins that exert control over specific mRNAs, as
      exemplified by an endonuclease that was found to directly cleave interleukin-6
      mRNA. Together, these systems make up an extensive regulatory network that
      controls decay rates of individual mRNAs in a precise manner and thereby
      orchestrates the dynamic expression of many factors essential for adaptive and
      innate immune responses. In this review, we provide an overview of relevant
      factors regulated at the level of mRNA stability, summarize RNA-binding proteins
      and miRNAs that control their degradation rates, and discuss signaling pathways
      operating within this regulatory network.

PMID- 21956943
TI  - Nuclear quality control of RNA polymerase II transcripts.
AB  - Eukaryotic RNA polymerase II produces an astounding diversity of transcripts.
      These may need to be 5(') capped, spliced, polyadenylated, and packaged with
      proteins before their export to the cytoplasm. Unscheduled accumulation of any
      RNA species can interfere with normal RNA metabolism and poses a serious hazard
      to cells. Yet, given the amount of primary transcripts and the complexity of the
      RNA maturation process, production of aberrant RNA species is unavoidable. Cells,
      therefore, employ nuclear RNA quality control mechanisms to rapidly degrade,
      actively retain, or transcriptionally silence unwanted RNAs. Pathways that
      monitor mRNA production are best understood and similar pathways are employed to
      destroy transcriptional noise. Finally, related mechanisms also contribute to
      gene regulation during normal growth.

PMID- 21956942
TI  - The role of AUF1 in regulated mRNA decay.
AB  - Messenger ribonucleic acid (mRNA) turnover is a major control point in gene
      expression. In mammals, many mRNAs encoding inflammatory cytokines, oncoproteins,
      and G-protein-coupled receptors are destabilized by the presence of AU-rich
      elements (AREs) in their 3'-untranslated regions. Association of ARE-binding
      proteins (AUBPs) with these mRNAs promotes rapid mRNA degradation. ARE/poly(U)
      binding/degradation factor 1 (AUF1), one of the best-characterized AUBPs, binds
      to many ARE-mRNAs and assembles other factors necessary to recruit the mRNA
      degradation machinery. These factors include translation initiation factor eIF4G,
      chaperones hsp27 and hsp70, heat-shock cognate protein hsc70, lactate
      dehydrogenase, poly(A)-binding protein, and other unidentified proteins. Numerous
      signaling pathways alter the composition of this AUF1 complex of proteins to
      effect changes in ARE-mRNA degradation rates. This review briefly describes the
      roles of mRNA decay in gene expression in general and ARE-mediated decay (AMD) in
      particular, with a focus on AUF1 and the different modes of regulation that
      govern AUF1 involvement in AMD.

PMID- 21956944
TI  - The role of posttranslational modifications in the assembly of stress granules.
AB  - Stress granules (SGs) are aggregates of translationally silenced messenger
      ribonucleoprotein (mRNP) complexes induced by oxidative, osmotic, hypoxic,
      thermal, viral, and genotoxic stresses. Over the past decade, extensive research
      has identified key components of SGs, their molecular interactions, and impact on
      stress-induced reprogramming of protein expression and cell survival. However,
      studies defining the signaling pathways that modulate SG assembly have only been
      launched recently. These studies reveal that posttranslational modifications of
      selected SG proteins play important roles in the regulation of SG assembly and
      function. Here we provide an overview of the signaling pathways and
      posttranslational protein modifications that regulate the assembly and function
      of SGs.

PMID- 21956945
TI  - Tissue-specific mechanisms of alternative polyadenylation: testis, brain, and
      beyond.
AB  - Changing the position of the poly(A) tail in an mRNA--alternative polyadenylation
      -is an important mechanism to increase the diversity of gene expression,
      especially in metazoans. Alternative polyadenylation often occurs in a tissue- or
      developmental stage-specific manner and can significantly affect gene activity by
      changing the protein product generated, the stability of the transcript, its
      localization, or its translatability. Despite the important regulatory effects
      that alternative polyadenylation have on gene expression, only a sparse few
      examples have been mechanistically characterized. Here, we review the known
      mechanisms for the control of alternative polyadenylation, catalog the tissues
      that demonstrate a propensity for alternative polyadenylation, and focus on the
      proteins that are known to regulate alternative polyadenylation in specific
      tissues. We conclude that the field of alternative polyadenylation remains in its
      infancy, with possibilities for future investigation on the horizon. Given the
      profound effect alternative polyadenylation can have on gene expression and human
      health, improved understanding of alternative polyadenylation could lead to
      numerous advances in control of gene activity.

PMID- 21956946
TI  - Evaluation of variance estimators for the concentration and health achievement
      indices: a Monte Carlo simulation.
AB  - Although the concentration index (CI) and the health achievement index (HAI) have
      been extensively used, previous studies have relied on bootstrapping to compute
      the variance of the HAI, whereas competing variance estimators exist for the CI.
      This paper provides methods of statistical inference for the HAI and compares the
      available variance estimators for both the CI and the HAI using Monte Carlo
      simulation. Results for both the CI and the HAI suggest that analytical methods
      and bootstrapping are well behaved. The convenient regression method gives
      standard errors close to the other methods, provided the CI is not too large (<
      0.2), but otherwise tends to understate the standard errors. In our simulation
      setting, the improvement from the Newey-West correction over the convenient
      regression method has mixed evidence when the CI <= 0.1 and is modest when the CI
      > 0.1. Published 2011. This article is a US Government work and is in the public
      domain in the USA.

PMID- 21956947
TI  - Modeling data with structural and temporal correlation using lower level and
      higher level multilevel models.
AB  - Novel imaging techniques are playing an increasingly important role in drug
      development, providing insight into the mechanism of action of new chemical
      entities. The data sets obtained by these methods can be large with complex inter
      relationships, but the most appropriate statistical analysis for handling this
      data is often uncertain--precisely because of the exploratory nature of the way
      the data are collected. We present an example from a clinical trial using
      magnetic resonance imaging to assess changes in atherosclerotic plaques following
      treatment with a tool compound with established clinical benefit. We compared two
      specific approaches to handle the correlations due to physical location and
      repeated measurements: two-level and four-level multilevel models. The two
      methods identified similar structural variables, but higher level multilevel
      models had the advantage of explaining a greater proportion of variation, and the
      modeling assumptions appeared to be better satisfied.

PMID- 21956948
TI  - Indirect comparisons in the comparative efficacy and non-inferiority settings.
AB  - International Conference on Harmonization E10 concerns non-inferiority trials and
      the assessment of comparative efficacy, both of which often involve indirect
      comparisons. In the non-inferiority setting, there are clinical trial results
      directly comparing an experimental treatment with an active control, and clinical
      trial results directly comparing the active control with placebo, and there is an
      interest in the indirect comparison of the experimental treatment with placebo.
      In the comparative efficacy setting, there may be separate clinical trial results
      comparing each of two treatments with placebo, and there is interest in an
      indirect comparison of the treatments. First, we show that the sample size
      required for a trial intended to demonstrate superiority through an indirect
      comparison is always greater than the sample size required for a direct
      comparison. In addition, by introducing the concept of preservation of effect, we
      show that the hypothesis addressed in the two settings is identical. Our main
      result concerns the logical inconsistency between a reasonable criterion for
      preference of an experimental treatment to a standard treatment and existing
      regulatory guidance for approval of the experimental treatment on the basis of an
      indirect comparison. Specifically, the preferred treatment will not always meet
      the criterion for regulatory approval. This is due to the fact that the
      experimental treatment bears the burden of overcoming the uncertainty in the
      effect of the standard treatment. We consider an alternative approval criterion
      that avoids this logical inconsistency.

PMID- 21956949
TI  - Active controlled studies in antibiotic drug development.
AB  - The increasing concern of antibacterial resistance has been well documented, as
      has the relative lack of antibiotic development. This paradox is in part due to
      challenges with clinical development of antibiotics. Because of their rapid
      progression, untreated bacterial infections are associated with significant
      morbidity and mortality. As a consequence, placebo-controlled studies of new
      agents are unethical. Rather, pivotal development studies are mostly conducted
      using non-inferiority designs versus an active comparator. Further, infections
      because of comparator-resistant isolates must usually be excluded from the trial
      programme. Unfortunately, the placebo-controlled data classically used in support
      of non-inferiority designs are largely unavailable for antibiotics. The only
      available data are from the 1930s and 1940s and their use is associated with
      significant concerns regarding constancy and assay sensitivity. Extended public
      debate on this challenge has led to proposed solutions by some in which these
      concerns are addressed by using very conservative approaches to trial design,
      endpoints and non-inferiority margins, in some cases leading to potentially
      impractical studies. To compound this challenge, different Regulatory Authorities
      seem to be taking different approaches to these key issues. If harmonisation does
      not occur, antibiotic development will become increasingly challenging, with the
      risk of further decreases in the amount of antibiotic drug development. However
      with clarity on Regulatory requirements and an ability to feasibly conduct global
      development programmes, it should be possible to bring much needed additional
      antibiotics to patients.

PMID- 21956950
TI  - Adjusting for covariates in non-inferiority studies with margins defined as risk
      differences.
AB  - Adjusting for covariates makes efficient use of data and can improve the
      precision of study results or even reduce sample sizes. There is no easy way to
      adjust for covariates in a non-inferiority study for which the margin is defined
      as a risk difference. Adjustment is straightforward on the logit scale, but
      reviews of clinical studies suggest that the analysis is more often conducted on
      the more interpretable risk-difference scale. We examined four methods that allow
      for adjustment on the risk-difference scale: stratified analysis with Cochran
      Mantel-Haenszel (CMH) weights, binomial regression with an identity link, the use
      of a Taylor approximation to convert results from the logit to the risk
      difference scale and converting the risk-difference margin to the odds-ratio
      scale. These methods were compared using simulated data based on trials in HIV.
      We found that the CMH had the best trade-off between increased efficiency in the
      presence of predictive covariates and problems in analysis at extreme response
      rates. These results were shared with regulatory agencies in Europe and the USA,
      and the advice received is described.

PMID- 21956951
TI  - Complex shapes and dynamics of dissolving drops of dichloromethane.

PMID- 21956952
TI  - Concise review: transmissible animal tumors as models of the cancer stem-cell
      process.
AB  - Tasmanian devil facial tumor disease (DFTD) and canine transmissible venereal
      tumor (CTVT) are highly unusual cancers capable of being transmitted between
      animals as an allograft. The concept that these tumors represent a cancer stem
      cell process has never been formally evaluated. For each, evidence of self
      renewal is found in the natural history of these tumors in the wild, tumor
      initiation in recipient animals, and serial transplantation studies. Additional
      data for stem-cell-specific genes and markers in DFTD also exist. Although both
      tumor types manifest as undifferentiated cancers, immunocytohistochemistry
      supports a histiocytic phenotype for CTVT and a neural crest origin, possibly a
      Schwann-cell phenotype, for DFTD. In these data, differential expression of
      lineage markers is seen which may suggest some capacity for differentiation
      toward a heterogeneous variety of cell types. It is proposed that DFTD and CTVT
      may represent and may serve as models of the cancer stem-cell process, but formal
      investigation is required to clarify this. Appreciation of any such role may act
      as a stimulus to ongoing research in the pathology of DFTD and CTVT, including
      further characterization of their origin and phenotype and possible therapeutic
      approaches. Additionally, they may provide valuable models for future studies of
      their analogous human cancers, including any putative CSC component.

PMID- 21956953
TI  - Cytoprotective effect of 20S-Rg3 on benzo[a]pyrene-induced DNA damage.
AB  - Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon ubiquitously existing
      in the environment. Its metabolites have been shown to cause DNA damage and
      cellular dysfunction in humans. Panax ginseng C.A. Meyer is a Chinese medicinal
      herb, and ginsenosides are the main active constituent of ginseng. Accumulating
      evidence had indicated that ginseng extract and ginsenosides possess
      cytoprotective effects. In this study, the protective effect of ginsenosides on
      BaP-induced DNA damage in human dermal fibroblasts (HDFs) and HepG2 cells was
      investigated. The genotoxic effect of BaP was measured by the comet assay.
      Results showed that tail moment was increased in BaP-treated cells, but
      cotreatment of ginsenoside 20(S)-Rg3 can significantly decrease BaP-induced DNA
      damage. A downstream mechanistic study revealed that 20(S)-Rg3 increased the gene
      expression of an important phase II detoxifying enzyme NAD(P)H:quinine
      oxidoreductase 1. The effect was also associated with the activation of protein
      kinase B (Akt) and nuclear translocation of nuclear factor erythroid 2-related
      factor 2 (Nrf2). These results indicated that 20(S)-Rg3 might protect HDFs from
      BaP-induced DNA damage through the activation of the phosphatidylinositol 3
      kinase/Akt/Nrf2 pathway. Our results also demonstrated that 20(S)-Rg3 is a
      functional ligand of pregnane X receptor (PXR), a nuclear receptor that mediates
      the induction of drug clearance pathways. Subsequent knockdown of PXR expression
      by small interfering RNA confirmed the involvement of PXR on the protective
      effects of 20(S)-Rg3 against BaP-induced DNA damage. In summary, ginsenoside
      20(S)-Rg3 can protect against BaP-induced genotoxicity in human cells, suggesting
      that ginseng may serve as a natural cytoprotective agent against environmental
      carcinogens.

PMID- 21956954
TI  - Moving towards evidence-based policy and program planning in multiple
      micronutrient interventions for children: symposium summary.
AB  - This article provides a summary of the symposium "Multiple Micronutrient
      Interventions during Early Childhood: Moving toward Evidence-Based Policy and
      Program Planning." The symposium reviewed the strength of evidence of multiple
      micronutrient interventions on child health, growth, and development, case
      examples demonstrating how information from program evaluations and the local
      context can be used to improve program design and performance, and the process by
      which evidence evolves, resulting in guidelines for policy-makers and program
      managers. The presentations highlighted the importance of an interactive platform
      at the country level where the scientific community and country stakeholders
      exchange ideas, develop a priority implementation research agenda, and clarify
      key issues to generate and modify policy and programs based on the best evidence
      available and the ability to deliver results in real time.

PMID- 21956956
TI  - Flavonoid-rich cocoa consumption affects multiple cardiovascular risk factors in
      a meta-analysis of short-term studies.
AB  - A growing body of evidence suggests that the consumption of foods rich in
      polyphenolic compounds, particularly cocoa, may have cardioprotective effects. No
      review, however, has yet examined the effect of flavonoid-rich cocoa (FRC) on all
      major cardiovascular risk factors or has examined potential dose-response
      relationships for these effects. A systematic review and meta-analysis of
      randomized, controlled trials was performed to evaluate the effect of FRC on
      cardiovascular risk factors and to assess a dose-response relationship. Inclusion
      and exclusion criteria as well as dependent and independent variables were
      determined a priori. Data were collected for: blood pressure, pulse, total
      cholesterol, HDL cholesterol, LDL cholesterol, TG, BMI, C-reactive protein, flow
      mediated vascular dilation (FMD), fasting glucose, fasting insulin, serum
      isoprostane, and insulin sensitivity/resistance indices. Twenty-four papers, with
      1106 participants, met the criteria for final analysis. In response to FRC
      consumption, systolic blood pressure decreased by 1.63 mm Hg (P = 0.033), LDL
      cholesterol decreased by 0.077 mmol/L (P = 0.038), and HDL cholesterol increased
      by 0.046 mmol/L (P = 0.037), whereas total cholesterol, TG, and C-reactive
      protein remained the same. Moreover, insulin resistance decreased (HOMA-IR: -0.94
      points; P < 0.001), whereas FMD increased (1.53%; P < 0.001). A nonlinear dose
      response relationship was found between FRC and FMD (P = 0.004), with maximum
      effect observed at a flavonoid dose of 500 mg/d; a similar relationship may exist
      with HDL cholesterol levels (P = 0.06). FRC consumption significantly improves
      blood pressure, insulin resistance, lipid profiles, and FMD. These short-term
      benefits warrant larger long-term investigations into the cardioprotective role
      of FRC.

PMID- 21956955
TI  - Preschool iron-folic acid and zinc supplementation in children exposed to iron
      folic acid in utero confers no added cognitive benefit in early school-age.
AB  - In Nepal, antenatal iron-folic acid supplementation improved aspects of
      intellectual, executive, and fine motor function among school-age children. We
      examined the impact of added zinc to the maternal antenatal supplement (M-IFAZn)
      and preschool supplementation from 12 to 36 mo with iron-folic acid (C-IFA) +/-
      zinc (C-IFAZn) on cognitive outcomes compared to maternal iron-folic acid (M-IFA)
      alone. Children 7-9 y old (n = 780) who participated in early childhood
      micronutrient supplementation trial during 2001-2004 and whose mothers
      participated in an antenatal micronutrient supplementation between 1999 and 2001
      were followed for cognitive assessments in 2007-2009. Using multivariate analysis
      of variance and adjusting for confounders, M-IFA with child supplementation
      (either C-IFA or C-IFAZn) did not impact scores on the tests of general
      intelligence (Universal Nonverbal Intelligence Test), and executive function
      (Stroop and go/no go tests) relative to the M-IFA alone. However, children in the
      C-IFAZn group had slightly lower scores on the backward digit span (-0.29, 95%
      CI: -0.55, -0.04) and Movement Assessment Battery for Children (1.33, 95% CI:
      0.26, 2.40) relative to the referent group, whereas both C-IFA (-1.92, 95% CI: 
      3.12, -0.71) and C-IFAZn (-1.78, 95% CI: -2.63, -0.92) produced somewhat lower
      finger tapping test scores (fine motor skills). The combination of M-IFAZn and C
      IFA or C-IFAZn did not lead to any outcome differences relative to M-IFA alone.
      Preschool iron-folic acid +/- zinc to children exposed to iron-folic acid in
      utero or addition of zinc to maternal iron-folic acid conferred no additional
      benefit to cognitive outcomes assessed in early school age. The late timing of
      supplementation during preschool may explain the lack of impact of iron and/or
      zinc.

PMID- 21956957
TI  - The Program Assessment Guide: an approach for structuring contextual knowledge
      and experience to improve the design, delivery, and effectiveness of nutrition
      interventions.
AB  - As evidence from small-scale trials has accumulated concerning the efficacy of
      low-cost interventions to address undernutrition, the design, implementation, and
      strengthening of large-scale programs to deliver these interventions has become a
      high priority. This scaling up process involves a large number of technical,
      logistical, administrative, political, and social considerations and little
      research exists on how to address these in a systematic way. This paper
      introduces the Program Assessment Guide (PAG), a set of analysis and decision
      tools that seeks to fill this gap, and reports on its application in Kyrgyzstan
      and Bolivia. The PAG places a special focus on eliciting and systematizing
      contextual knowledge and experience through a structured, participatory workshop
      and is grounded in theory, principles, and experience from program planning,
      management, change management, and intervention planning. When applied in
      Kyrgyzstan and Bolivia, the PAG was successful in helping workshop participants
      identify key implementation bottlenecks, questionable assumptions in the program
      theory, and feasible ways to address some of the shortcomings. These experiences
      also identified the need for a number of modifications to the PAG related to the
      workshop design itself, the preparations prior to the workshop, and follow-up
      after the workshop. The PAG represents one approach for strengthening decisions
      related to the design and large-scale implementation of interventions. The
      development and full-scale testing of alternative methods such as these for
      strengthening program analysis and decision making is an important and
      intellectually challenging subject for further research.

PMID- 21956959
TI  - Do multiple micronutrient interventions improve child health, growth, and
      development?
AB  - Micronutrient deficiencies are common and often co-occur in many developing
      countries. Several studies have examined the benefits of providing multiple
      micronutrient (MMN) interventions during pregnancy and childhood, but the
      implications for programs remain unclear. The key objective of this review is to
      summarize what is known about the efficacy of MMN interventions during early
      childhood on functional outcomes, namely, child health, survival, growth, and
      development, to guide policy and identify gaps for future research. We identified
      review articles including meta-analyses and intervention studies that evaluated
      the benefits of MMN interventions (3 or more micronutrients) in children (<5 y of
      age) using Pubmed and EMBASE. Several controlled trials (n = 45) and meta
      analyses (n = 6) have evaluated the effects of MMN interventions primarily for
      child morbidity, anemia, and growth. Two studies found no effects on child
      mortality. The findings for respiratory illness and diarrhea are mixed, although
      suggestive of benefit when provided as fortified foods. There is evidence from
      several controlled trials (>25) and 2 meta-analyses that MMN interventions
      improve hemoglobin concentrations and reduce anemia, but the effects were small
      compared to providing only iron or iron with folic acid. Two recent meta-analyses
      and several intervention trials also indicated that MMN interventions improve
      linear growth compared to providing a placebo or single nutrients. Much less is
      known about the effects on MMN interventions during early childhood on motor and
      mental development. In summary, MMN interventions may result in improved outcomes
      for children in settings where micronutrient deficiencies are widespread.

PMID- 21956958
TI  - Insulin-like growth factor-1 increases bone calcium accumulation only during
      rapid growth in female rats.
AB  - Calcium retention varies with developmental state, which may be partially under
      the control of insulin-like growth factor 1 (IGF-1). IGF-1 levels can be
      manipulated through dietary and therapeutic interventions. We investigated the
      relationship between IGF-1 endogenous production and calcium utilization and bone
      accretion during growth as well as the effects of IGF-1 treatment on calcium
      utilization during rapid and slowed growth in intact female Sprague-Dawley rats.
      In 33 rats killed at 11 time points (n = 3 each) from age 4 to 24 wk, femoral and
      vertebral bone mass were paralleled by plasma IGF-1 up to 9 wk. Fractional
      calcium absorption was maximal at 9 wk, reduced by one-half at 12 wk, and there
      was no further change at 20 wk. From this study, we selected 2 stages of growth,
      rapid and slow, for a subsequent intervention study. A 4-wk intervention was
      initiated at 6 or 8 wk when rats (n = 15/group) received either continuous rhIGF
      1/IGF binding protein 3 (IGFBP3) infusion (0.3 mg/d) or vehicle (control) by
      osmotic mini-pumps. In rapidly growing IGF-1/IGFBP3-treated rats compared to
      controls, but not in slowly growing treated compared to control rats, IGF-1
      treatment increased (P < 0.05) calcium absorption (35 vs. 21%), bone calcium
      balance (0.55 vs. 0.3 mmol/d), and femoral calcium content (31 vs. 24% of dry
      weight). Exogenous IGF-1/IGFBP3 treatment increased calcium accretion during
      rapid growth, but rats past rapid growth were no longer as sensitive to this dose
      of IGF-1/IGFBP3. Thus, interventions designed to improve bone mass through
      increased IGF-1 will have the greatest impact during rapid growth.

PMID- 21956961
TI  - Multiple micronutrient interventions during early childhood: moving towards
      evidence-based policy and program planning.
AB  - There is considerable evidence that micronutrient deficiencies affect child
      health and well-being. Although the benefits of strategies that improve diet
      quality and micronutrient density of foods consumed by small children combined
      with reducing infections are well recognized as optimal for promoting young child
      growth and development, they have been difficult to accomplish in many resource
      poor settings and few countries have clear policies in support of integrated
      strategies to control micronutrient deficiencies. The focus of a recent symposium
      that was part of the Annual Meeting of the ASN held in Anaheim in April 2010 was
      on how we as the scientific community can help governments and organizations
      design nutrition and specifically micronutrient policies and programs based on
      the available evidence; papers that were based on the invited presentations are
      included in this Supplement. The first paper is a critical review of the current
      state of knowledge regarding the efficacy and effectiveness of multiple
      micronutrient interventions in developing country settings, followed by a paper
      that reviews key issues in evidenced-based policy and program development and
      includes a relevant example from Mexico where this has occurred. These are
      followed by a paper that describes a systematic process that is being proposed as
      a method to guide policy makers and program developers to strengthen program
      design and performance. The final paper is a summary that highlights areas where
      the nutrition research community has been successful in translating evidence into
      policy-relevant advice and where we can improve in this process.

PMID- 21956960
TI  - Supplementation with alpha-tocopherol or beta-carotene reduces serum
      concentrations of vascular endothelial growth factor-D, but Not -A or -C, in male
      smokers.
AB  - Evidence from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study
      suggests that vitamin E and beta-carotene supplement use may influence the risk
      of several cancers. Vascular endothelial growth factors (VEGF) are proteins
      involved in angiogenesis, an important requirement for tumor growth and
      metastasis. Thus, vitamin E and beta-carotene may influence cancer risk through
      one or more VEGF. The ATBC Study was a randomized, double-blind, placebo
      controlled, primary cancer prevention trial in which participants were assigned
      to 1 of 4 supplementation groups based on a 2 * 2 factorial design: 1) alpha
      tocopherol (vitamin E); 2) beta-carotene; 3) both; or 4) placebo. For the present
      study, 100 cancer-free participants with follow-up serum available were randomly
      selected from each intervention group. VEGF-A, -C, and -D concentrations were
      measured by ELISA in serum obtained at baseline and after at least 2 y of
      supplementation. Differences in change in VEGF levels from baseline to follow-up
      between intervention groups were assessed using the ANOVA test. Change in VEGF-A
      and VEGF-C concentrations between baseline and follow-up did not differ by
      intervention group (P = 0.45 and 0.29, respectively). The decrease in the serum
      VEGF-D concentration was greater in the men supplemented with alpha-tocopherol (
      9.7 +/- 2.5%) or beta-carotene (-8.5 +/- 2.7%) and tended to be greater in those
      supplemented with both (-6.8 +/- 2.4%) compared to the placebo group, in which
      there was no change (-0.4 +/- 3.0%) (P = 0.03). In this population of male
      smokers, supplementation with alpha-tocopherol or beta-carotene was associated
      with a decrease in VEGF-D levels over time. Although the mechanism through which
      these supplements affect cancer etiolog remains unclear, our results support the
      hypothesis that vitamin E and beta-carotene may influence cancer progression
      through VEGF-mediated lymphangiogenesis.

PMID- 21956962
TI  - Evaluation for program decision making: a case study of the Oportunidades program
      in Mexico.
AB  - Although evaluation is now an integral part of the design and implementation of
      public programs in many countries, there is growing recognition that the
      utilization of evaluation results for improving implementation and decision
      making, particularly in developing countries, is limited. The objective of this
      paper is to describe the process by which the external impact evaluation has been
      used to increase the potential of Oportunidades to improve nutritional outcomes
      of the beneficiary population through modifications to its design and operation.
      We will summarize a series of studies that have guided this process and focus on
      key aspects that have facilitated the utilization of evaluation results for
      decision making in the program. Implementation of research to document the impact
      of programs and the publication of such findings in peer reviewed journals,
      although vital for improving our evidence base and for the advancement of
      researchers within the current academic system, is not enough to ensure that the
      program itself will benefit from the evaluation. The use of evaluation results as
      a basis for modifications to the design and implementation of the nutrition
      component of Oportunidades was favored by open dialogue among all sectors
      involved in the program and the evaluation team and a long-term commitment on the
      part of all those involved. We think that the lessons learnt from this process
      are relevant for other programs, even where resources may be limited.

PMID- 21956963
TI  - A three-part, mixed-effects model to estimate the habitual total vitamin D intake
      distribution from food and dietary supplements in Dutch young children.
AB  - Statistical modeling of habitual micronutrient intake from food and dietary
      supplements using short-term measurements is hampered by heterogeneous variances
      and multimodality. Summing short-term intakes from food and dietary supplements
      prior to simple correction for within-person variation (first add then shrink)
      may produce estimates of habitual total micronutrient intake so badly biased as
      to be smaller than estimates of habitual intake from food sources only. A 3-part
      model using a first shrink then add approach is proposed to estimate the habitual
      micronutrient intake from food among nonsupplement users, food among supplement
      users, and supplements. The population distribution of habitual total
      micronutrient intake is estimated by combining these 3 habitual intake
      distributions, accounting for possible interdependence between Eq. 2 and 3. The
      new model is an extension of a model developed by the USA National Cancer
      Institute. Habitual total vitamin D intake among young children was estimated
      using the proposed model and data from the Dutch food consumption survey (n =
      1279). The model always produced habitual total intakes similar to or higher than
      habitual intakes from food sources only and also preserved the multimodal shape
      of the observed total vitamin D intake distribution. This proposed method
      incorporates several sources of covariate information that should provide more
      precise estimates of the habitual total intake distribution and the proportion of
      the population with intakes below/above cutpoint values. The proposed methodology
      could be useful for other complex situations, e.g. where high concentrations of
      micronutrients appear in episodically consumed foods.

PMID- 21956964
TI  - The salivary proteome: challenges and perspectives.
AB  - We provide a brief overview of the salivary proteome but with an emphasis on the
      major challenges in protein identification and quantitation. Precautions are
      necessary to avoid proteolysis, deglycosylation and dephosphorylation of salivary
      proteins by microbial and host enzymes in saliva. Many proteins are
      differentially expressed in secretions from different salivary glands and their
      proportional contributions to saliva vary with the flow rate. The total protein
      concentration in the secretion from any one gland varies considerably, depending
      on factors such as flow rate, duration of stimulation, nature of the stimulus and
      circadian rhythms. Many plasma proteins enter saliva via gingival crevicular
      fluid, of which there are increased amounts in persons with gingivitis or
      periodontal disease. These factors must be taken into account in the
      identification of potential biomarkers for different oral or systemic diseases.

PMID- 21956966
TI  - Tin(IV) oxide coatings from hybrid organotin/polymer nanoparticles.
AB  - Tin dioxide coatings are widely applied in glasses and ceramics to improve not
      only optical, but also mechanical properties. In this work, we report a new
      method to prepare SnO(2) coatings from aqueous dispersions of polymer/organotin
      hybrid nanoparticles. Various liquid organotin compounds were encapsulated in
      polymeric nanoparticles synthesized by miniemulsion polymerization. Large amounts
      of tetrabutyltin and bis(tributyltin) could be successfully incorporated in cross
      linked and noncross-linked polystyrene nanoparticles that served as sacrificial
      templates for the formation of tin oxide coatings after etching with oxygen
      plasma or calcination. Cross-linked polystyrene particles containing
      bis(tributyltin)--selected for having a high boiling point--were found to be
      especially suited for the oxide coating formation. The content of metal in the
      particles was up to 12 wt %, and estimations by thermogravimetrical indicated
      that at least 96% of the total organotin compound was converted to SnO(2). The
      resulting coatings were mainly identified as tetragonal SnO(2) (cassiterite) by X
      ray diffraction, although a coexistence of this phase with orthorhombic SnO(2)
      was observed for samples prepared with bis(tributyltin).

PMID- 21956967
TI  - Alternative mRNA polyadenylation in eukaryotes: an effective regulator of gene
      expression.
AB  - Alternative RNA processing mechanisms, including alternative splicing and
      alternative polyadenylation, are increasingly recognized as important regulators
      of gene expression. This article will focus on what has recently been described
      about alternative polyadenylation in development, differentiation, and disease in
      higher eukaryotes. We will also describe how the evolving global methodologies
      for examining the cellular transcriptome, both experimental and bioinformatic,
      are revealing new details about the complex nature of alternative 3(') end
      formation as well as interactions with other RNA-mediated and RNA processing
      mechanisms.

PMID- 21956968
TI  - RNA diagnostics: real-time RT-PCR strategies and promising novel target RNAs.
AB  - Ribonucleic acid (RNA) is a multifunctional type of molecule, playing critical
      roles in protein biosynthesis and regulation. In recent years, suppression of
      protein translation by so-called microRNAs came into the focus of research,
      especially because deregulation of this process has been shown to play a role in
      malignant transformation. Furthermore, RNA molecules circulating in the blood
      have been revealed as a novel class of markers for diagnosis of cancers.
      Moreover, genetic information of some pathogens is stored as RNA, allowing their
      sensitive detection using nucleic acid amplification techniques. In this article,
      the principle of detecting different RNA types by real-time reverse-transcription
      polymerase chain reaction applications is described. Furthermore, the emerging
      use of microRNA and circulating RNA profiles complementing the broad spectrum of
      RNA diagnosis is discussed.

PMID- 21956969
TI  - A central role for RNA in the induction and biological activities of type 1
      interferons.
AB  - In mammals the type 1 interferon (IFN) system functions as the primary innate
      antiviral defense and more broadly as a stress response and regulator of diverse
      homeostatic mechanisms. RNA plays a central role in the induction of IFN and in
      its biologic activities. Cellular toll-like receptors (TLR), RIG-I-like receptors
      (RLR), and nucleotide organization domain-like receptors (NLR) sense pathogen-
      and danger-associated RNAs as nonself based on structural features and
      subcellular location that distinguish them from ubiquitous host RNAs. Detection
      of nonself RNAs activates signaling pathways to induce IFN transcription and
      secretion. In turn, IFN binds cell surface receptors to initiate signaling that
      results in the induction of IFN-stimulated genes (ISGs) that mediate its biologic
      activities. RNA also plays a critical role in this effector phase of the IFN
      system, serving as an activator of enzyme activity for protein kinase RNA
      dependent (PKR) and oligoadenylate synthetase (OAS), and as a substrate for 2('),
      5(') -linked oligoadenylate dependant-endoribonuclease (RNase-L). In contrast to
      the transcriptional response induced by RNA receptors, these key ISGs mediate
      their activities primarily through post transcriptional mechanisms to regulate
      the translation and stability of host and microbial RNAs. Together RNA-sensing
      and RNA-effector molecules comprise a network of coordinately regulated proteins
      with integrated feedback and feed-forward loops that tightly regulate the
      cellular response to RNA. This stringent regulation is essential to prevent
      deleterious effects of uncontrolled IFN expression and effector activation. In
      light of this extensive crosstalk, targeting key mediators of the cellular
      response to RNA represents a viable strategy for therapeutic modulation of immune
      function and treatment of diseases in which this response is dysregulated (e.g.,
      cancer).

PMID- 21956970
TI  - mRNA 3' end processing and more--multiple functions of mammalian cleavage factor
      I-68.
AB  - The formation of defined 3(') ends is an important step in the biogenesis of
      mRNAs. In eukaryotic cells, all mRNA 3(') ends are generated by endonucleolytic
      cleavage of primary transcripts in reactions that are essentially
      posttranscriptional. Nevertheless, 3(') end formation is tightly connected to
      transcription in vivo, and a link with mRNA export to the cytoplasm has been
      postulated. Here, we briefly review the current knowledge about the two types of
      mRNA 3(') end processing reactions, cleavage/polyadenylation and histone RNA
      processing. We then focus on factors shared between these two reactions. In
      particular, we discuss evidence for new functions of the mammalian cleavage
      factor I subunit CF I(m) 68 in histone RNA 3(') processing and in the export of
      mature mRNAs from the nucleus to the cytoplasm.

PMID- 21956971
TI  - Immunoglobulin heavy chain gene regulation through polyadenylation and splicing
      competition.
AB  - The immunoglobulin heavy chain (IgH) genes, which encode one of the two chains of
      antibody molecules, were the first cellular genes shown to undergo
      developmentally regulated alternative RNA processing. These genes produce two
      different mRNAs from a single primary transcript. One mRNA is cleaved and
      polyadenylated at an upstream poly(A) signal while the other mRNA removes this
      poly(A) signal by RNA splicing and is cleaved and polyadenylated at a downstream
      poly(A) site. A broad range of studies have been performed to understand the
      mechanism of IgH RNA processing regulation during B lymphocyte development. The
      model that has emerged is much more complex than envisioned by the earliest view
      of regulation through poly(A) signal choice. Regulation requires that the IgH
      gene contain competing splice and cleavage-polyadenylation reactions with
      balanced efficiencies. Because non-IgH genes with these structural features also
      can be regulated, IgH gene-specific sequence elements are not required for
      regulation. Changes in cleavage-polyadenylation and RNA splicing, as well as pol
      II elongation, all contribute to IgH developmental RNA processing regulation.
      Multiple factors are likely involved in the regulation during B lymphocyte
      maturation. Additional biologically relevant factors that contribute to IgH
      regulation remain to be identified and incorporated into a mechanistic model for
      regulation. Much of the work to date confirms the complex nature of IgH mRNA
      regulation and suggests that a thorough understanding of this control will remain
      a challenge. However, it is also likely that such understanding will help
      elucidate novel mechanisms of RNA processing regulation.

PMID- 21956972
TI  - Exonucleases and endonucleases involved in polyadenylation-assisted RNA decay.
AB  - RNA polyadenylation occurs in most forms of life, excluding a small number of
      biological systems. This posttranscriptional modification undertakes two roles,
      both of which influence the stability of the polyadenylated transcript. One is
      associated with the mature 3' ends of nucleus-encoded mRNAs in eukaryotic cells
      and is important for nuclear exit, translatability, and longevity. The second
      form of RNA polyadenylation assumes an almost opposite role; it is termed
      'transient' and serves to mediate the degradation of RNA. Poly(A)-assisted RNA
      decay pathways were once thought to occur only in prokaryotes/organelles but are
      now known to be a common phenomenon, present in bacteria, organelles, archaea,
      and the nucleus and cytoplasm of eukaryotic cells, regardless of the fact that in
      some of these systems, stable polyadenylation exists as well. This article will
      summarize the current knowledge of polyadenylation and degradation factors
      involved in poly(A)-assisted RNA decay in the domains of life, focusing mainly on
      that which occurs in prokaryotes and organelles. In addition, it will offer an
      evolutionary view of the development of RNA polyadenylation and degradation and
      the cellular machinery that is involved.

PMID- 21956973
TI  - MicroRNAs in cardiac hypertrophy: angels or devils.
AB  - MicroRNAs (miRNAs) are short noncoding RNA molecules that can regulate gene
      expression via affecting mRNA stability or translation efficiency. miRNAs mediate
      many important cellular processes and emerge as a newly discovered regulator of
      gene expression. In cardiac hypertrophy, miRNAs expression is aberrantly altered.
      Some of these miRNAs can promote cardiac hypertrophy, whereas others can inhibit
      the process. In this review, we summarize the up- and downregulated miRNAs during
      cardiac hypertrophy and discuss about their roles in cardiac hypertrophy. The
      studies on miRNAs shed new light on the mechanism of cardiac hypertrophy and
      suggest that they may be promising therapeutic targets in tackling cardiac
      hypertrophy.

PMID- 21956975
TI  - Structural cooperativity in histone H3 tail modifications.
AB  - Post-translational modifications of histone H3 tails have crucial roles in
      regulation of cellular processes. There is cross-regulation between the
      modifications of K4, K9, and K14 residues. The modifications on these residues
      drastically promote or inhibit each other. In this work, we studied the
      structural changes of the histone H3 tail originating from the three most
      important modifications; tri-methylation of K4 and K9, and acetylation of K14. We
      performed extensive molecular dynamics simulations of four types of H3 tails: (i)
      the unmodified H3 tail having no chemical modification on the residues, (ii) the
      tri-methylated lysine 4 and lysine 9 H3 tail (K4me3K9me3), (iii) the tri
      methylated lysine 4 and acetylated lysine 14 H3 tail (K4me3K14ace), and (iv) tri
      methylated lysine 9 and acetylated lysine 14 H3 tail (K9me3K14ace). Here, we
      report the effects of K4, K9, and K14 modifications on the backbone torsion
      angles and relate these changes to the recognition and binding of histone
      modifying enzymes. According to the Ramachandran plot analysis; (i) the dihedral
      angles of K4 residue are significantly affected by the addition of three methyl
      groups on this residue regardless of the second modification, (ii) the dihedral
      angle values of K9 residue are similarly altered majorly by the tri-methylation
      of K4 residue, (iii) different combinations of modifications (tri-methylation of
      K4 and K9, and acetylation of K14) have different influences on phi and psi
      values of K14 residue. Finally, we discuss the consequences of these results on
      the binding modes and specificity of the histone modifying enzymes such as DIM-5,
      GCN5, and JMJD2A.

PMID- 21956974
TI  - Local translation of mRNAs in neural development.
AB  - Growing axons encounter numerous developmental signals to which they must
      promptly respond in order to properly form complex neural circuitry. In the
      axons, these signals are often transduced into a local increase or decrease in
      protein levels. Contrary to the traditional view that the cell bodies are the
      exclusive source of axonal proteins, it is becoming increasingly clear not only
      that de novo protein synthesis takes place in axons, but also that it is required
      for the axons to respond to certain signals. Here we review the current knowledge
      of local mRNA translation in developing neurons with a special focus on protein
      synthesis occurring in axons and growth cones.

PMID- 21956976
TI  - Work stress and well-being in oncology settings: a multidisciplinary study of
      health care professionals.
AB  - OBJECTIVES: Staff working in oncology report high levels of work-related stress.
      This arises partly from the nature of clinical work, including practitioner
      perceptions of high demand and low control or high effort and low reward. This
      comparative study investigated the correlates of work stress in a
      multidisciplinary group of staff and the associations between staff perceptions
      of the work environment, emotional distress, job satisfaction and work-based
      social support. METHODS: This questionnaire study combined quantitative and
      qualitative assessment in a cohort sample of multidisciplinary staff (N = 85)
      working in a cancer centre in North East Scotland. Ethical approval was granted
      by the local Research Ethics Committee. This paper reports on the quantitative
      element of the study, RESULTS: Response rate was 50.6% (N = 85). Older, female
      and nursing and support staff were more likely to participate. Support staff
      reported the lowest perceptions of control, job satisfaction and managerial
      support. Radiographers reported the highest levels of job satisfaction, co-worker
      and managerial support. Nurses perceived lower decision control and job
      satisfaction than allied health professionals or doctors. In general, perceptions
      of decisional control and reward were protective of job satisfaction,
      particularly when work demands were high. Co-worker support was associated with
      perceptions of reduced effort, greater reward and increased satisfaction.
      Managerial support was also associated with greater control beliefs. Overall,
      sickness absence exceeded the 5% rates seen in other National Health Service
      surveys, whereas turnover intention rates were similar. CONCLUSION: The
      development and introduction of multilevel strategies to reduce demand, improve
      control and support perceptions are warranted, particularly for support staff.

PMID- 21956977
TI  - Effects of inositol supplementation in a cohort of mothers at risk of producing
      an NTD pregnancy.
AB  - Neural tube defects (NTDs), most commonly spina bifida and anencephaly, can be
      prevented with periconceptional intake of folic acid in about 70% of cases.
      Recurrence of NTDs despite supplementation of high dose of folic acid further
      suggests that a proportion of NTD cases might be resistant to folic acid.
      Moreover, heterogeneity of NTDs has been suggested in animal studies, indicating
      that only some sub-type of NTDs should be considered sensitive to folate intake.
      Inositol isomers (particularly myo- and chiro-inositol) can prevent folate
      resistant NTDs in the curly-tail mutant mouse, suggesting that some cases of
      human NTDs might benefit from inositol supplementation. In humans, lower inositol
      blood concentration was found in pregnant women carrying NTD fetuses, whereas a
      periconceptional combination therapy with folic acid associated with inositol has
      been linked to normal live births, despite high NTD recurrence risk. Fifteen
      pregnancies from 12 Caucasian women from different parts of Italy with at least
      one previous NTD-affected pregnancy underwent periconceptional combined myo
      inositol and folic acid supplementation. Maternal serum alpha-feto-protein levels
      were found in the normal range, and normal results on ultrasound examination were
      found in all the pregnancies that followed. No collateral effects or intense
      uterine contractions were demonstrated in this pilot study in any of the
      pregnancies after inositol supplementation, and seventeen babies were born
      without any type of NTD.

PMID- 21956978
TI  - Evaluation of the GeneXpert MTB/RIF assay for rapid diagnosis of tuberculosis and
      detection of rifampin resistance in pulmonary and extrapulmonary specimens.
AB  - Mycobacterium tuberculosis remains one of the most significant causes of death
      from an infectious agent. The rapid diagnosis of tuberculosis and detection of
      rifampin (RIF) resistance are essential for early disease management. The
      GeneXpert MTB/RIF assay is a novel integrated diagnostic device for the diagnosis
      of tuberculosis and rapid detection of RIF resistance in clinical specimens. We
      determined the performance of the MTB/RIF assay for rapid diagnosis of
      tuberculosis and detection of rifampin resistance in smear-positive and smear
      negative pulmonary and extrapulmonary specimens obtained from possible
      tuberculosis patients. Two hundred fifty-three pulmonary and 176 extrapulmonary
      specimens obtained from 429 patients were included in the study. One hundred ten
      (89 culture positive and 21 culture negative for M. tuberculosis) of the 429
      patients were considered to have tuberculosis. In pulmonary specimens,
      sensitivities were 100% (27/27) and 68.6% (24/35) for smear-positive and smear
      negative specimens, respectively. It had a lower sensitivity with extrapulmonary
      specimens: 100% for smear-positive specimens (4/4) and 47.7% for smear-negative
      specimens (21/44). The test accurately detected the absence of tuberculosis in
      all 319 patients without tuberculosis studied. The MTB/RIF assay also detected 1
      RIF-resistant specimen and 88 RIF-susceptible specimens, and the results were
      confirmed by drug susceptibility testing. We concluded that the MTB/RIF test is a
      simple method, and routine staff with minimal training can use the system. The
      test appeared to be as sensitive as culture with smear-positive specimens but
      less sensitive with smear-negative pulmonary and extrapulmonary specimens that
      include low numbers of bacilli.

PMID- 21956979
TI  - Dermatophyte identification using matrix-assisted laser desorption ionization
      time of flight mass spectrometry.
AB  - The performance of the Bruker Biotyper matrix-assisted laser desorption
      ionization-time of flight (MALDI-TOF) mass spectrometer (MS) for the
      identification of dermatophytes from clinical cultures was compared to that of
      dermatophyte identification using 28S rRNA gene sequencing. The MALDI Biotyper
      library (MBL; version 3.0) was used alone and in combination with a supplemented
      library containing an additional 20 dermatophyte spectra (S-MBL). Acquired
      spectra were interpreted using both the manufacturer-recommended scores (genus,
      >=1.7; species, >=2.0) and adjusted cutoff values established by this study
      (genus, >=1.5; species, >=1.7); identifications required a minimum 10% difference
      in scores between the top two different organisms to be considered correct. One
      hundred well-characterized, archived dermatophyte isolates and 71 fresh
      dermatophyte cultures were evaluated using both libraries and both sets of cutoff
      criteria. Collectively, the S-MBL significantly outperformed the MBL at both the
      genus (93% versus 37.4%; P < 0,0001) and species (59.6% versus 20.5%; P < 0.0001)
      levels when using the adjusted score criteria. Importantly, application of the
      lowered cutoff values significantly improved genus (P = 0.005)- and species (P <
      0.0001)-level identification for the S-MBL, without leading to an increase in
      misidentifications. MALDI-TOF MS is a cost-effective and rapid alternative to
      traditional or molecular methods for dermatophyte identification, provided that
      the reference library is supplemented to sufficiently encompass clinically
      relevant, intraspecies strain diversity.

PMID- 21956980
TI  - Impact of genomic sequence variability on quantitative PCR assays for diagnosis
      of polyomavirus BK infection.
AB  - Knowledge of polyomavirus BK (BKV) genomic diversity has greatly expanded. The
      implications of BKV DNA sequence variation for the performance of molecular
      diagnostic assays is not well studied. We analyzed 184 publically available VP-1
      sequences encompassing the BKV genomic region targeted by an in-house
      quantitative hydrolysis probe-based PCR assay. A perfect match with the PCR
      primers and probe was seen in 81 sequences. One Dun and 13 variant prototype
      oligonucleotides were synthesized as artificial targets to determine how they
      affected the performance of PCR. The sensitivity of detection of BKV in the PCR
      assay was a function of the viral genotype. Prototype 1 (BKV Dun) could be
      reliably detected at concentrations as low as 10 copies/MUl. However, consistent
      detection of all BKV variants was possible only at concentrations of 10,000
      copies/MUl or higher. For BKV prototypes with 2 or more mismatches (representing
      genotype IV, genotype II, and genotype 1c strains), the calculated viral loads
      were 0.57 to 3.26% of the expected values. In conclusion, variant BKV strains
      lower the sensitivity of detection and may have a substantial effect on
      quantitation of the viral load. Physicians need to be cognizant of these effects
      when interpreting the results of quantitative PCR testing in transplant
      recipients, particularly if there is a discrepancy between the clinical
      impression and the measured viral load.

PMID- 21956981
TI  - High-resolution melting-curve analysis of ligation-mediated real-time PCR for
      rapid evaluation of an epidemiological outbreak of extended-spectrum-beta
      lactamase-producing Escherichia coli.
AB  - Methods for the confirmation of nosocomial outbreaks of bacterial pathogens are
      complex, expensive, and time-consuming. Recently, a method based on ligation
      mediated PCR (LM/PCR) using a low denaturation temperature which produces
      specific melting-profile patterns of DNA products has been described. Our
      objective was to further develop this method for real-time PCR and high
      resolution melting analysis (HRM) in a single-tube system optimized in order to
      achieve results within 1 day. Following the optimization of LM/PCR for real-time
      PCR and HRM (LM/HRM), the method was applied for a nosocomial outbreak of
      extended-spectrum-beta-lactamase (ESBL)-producing and ST131-associated
      Escherichia coli isolates (n = 15) and control isolates (n = 29), including four
      previous clusters. The results from LM/HRM were compared to results from pulsed
      field gel electrophoresis (PFGE), which served as the gold standard. All isolates
      from the nosocomial outbreak clustered by LM/HRM, which was confirmed by gel
      electrophoresis of the LM/PCR products and PFGE. Control isolates that clustered
      by LM/PCR (n = 4) but not by PFGE were resolved by confirmatory gel
      electrophoresis. We conclude that LM/HRM is a rapid method for the detection of
      nosocomial outbreaks of bacterial infections caused by ESBL-producing E. coli
      strains. It allows the analysis of isolates in a single-tube system within a day,
      and the discriminatory power is comparable to that of PFGE.

PMID- 21956982
TI  - The N-acylneuraminate cytidyltransferase gene, neuA, is heterogenous in
      Legionella pneumophila strains but can be used as a marker for epidemiological
      typing in the consensus sequence-based typing scheme.
AB  - Sequence-based typing (SBT) is the internationally recognized standard method for
      genotyping Legionella pneumophila. To date all strains of serogroup 1 (SG1) and
      some of SGs 2 to 14 yield a seven-allele profile and can be assigned a sequence
      type (ST). However, for some strains belonging to SGs 2 to 14, the targeted
      region of the neuA gene could not be amplified using the published standard
      primers. We determined the DNA sequence of a neuA gene homolog located in the
      lipopolysaccharide synthesis locus of strain Dallas-1E. By using newly designed
      degenerate consensus primers based on the neuA homolog in strains Dallas-1E,
      Philadelphia-1, Paris, Lens, and Corby, we were able to obtain DNA sequences for
      all 48 non-SG1 strains which were untypeable by the standard method. Our data
      show that the neuA gene is present in all L. pneumophila strains but differs
      significantly in some non-SG1 strains at both the DNA and amino acid levels. The
      new primers can be used to amplify and sequence the neuA gene in all strains and
      can substitute for the standard primers. This offers the possibility of assigning
      an ST to all strains of L. pneumophila.

PMID- 21956983
TI  - Enterobius vermicularis in a 14-year-old girl's eye.
AB  - We report an unusual case of extraintestinal infection with adult Enterobius
      vermicularis worms in the nares and ocular orbit of a 14-year-old girl in
      Illinois. Only one other similar case has been reported in the English-language
      literature.

PMID- 21956984
TI  - Colorimetric nucleic acid testing assay for RNA virus detection based on circle
      to-circle amplification of padlock probes.
AB  - We developed a molecular diagnostic method for detection of RNA virus based on
      padlock probes and colorimetric readout. The feasibility of our approach was
      demonstrated by using detection of Crimean-Congo hemorrhagic fever (CCHF) virus
      as a model. Compared with conventional PCR-based methods, our approach does not
      require advanced equipment, involves easier assay design, and has a sensitivity
      of 10(3) viral copies/ml. By using a cocktail of padlock probes, synthetic
      templates representing different viral strain variants could be detected. We
      analyzed 34 CCHF patient samples, and all patients were correctly diagnosed when
      the results were compared to those of the current real-time PCR method. This is
      the first time that highly specific padlock probes have been applied to detection
      of a highly variable target sequence typical of RNA viruses.

PMID- 21956985
TI  - Lack of association between clinical outcome of Clostridium difficile infections,
      strain type, and virulence-associated phenotypes.
AB  - Clostridium difficile strain NAP1/027 (North American pulsed-field gel
      electrophoresis [PFGE] type 1 and PCR ribotype 027 [R027]) has been associated
      with recent outbreaks in North America and Europe. It has been associated with
      more severe disease symptoms, higher mortality rates, and greater risk of
      relapse. This strain is thought to produce more toxins and sporulate to higher
      levels. However, recent studies suggest that this may not always be the case. The
      objective of our study was to assess, in a nonoutbreak situation, whether
      specific strains, such as NAP1/027, were associated with more severe disease
      symptoms, higher toxin production, and/or greater sporulation in vitro. We
      isolated and characterized C. difficile strains from 21 patients with mild to
      moderate, severe, or complicated symptoms of C. difficile infection (CDI). The
      isolates were characterized by different molecular typing methods, including PCR
      ribotyping, tandem repeat sequence typing (TRST), and sequencing of the tcdC
      gene. Fourteen isolates were of PCR ribotype 027 with deletions in tcdC, but no
      association with severity or clinical outcome was found. We show by immunodot
      blot detection of toxins with monoclonal antibodies that all R027 isolates
      produced more TcdA and TcdB than other strains. On the other hand, they
      consistently produced fewer spores than non-R027 isolates. Taken together, our
      data suggest that NAP1/027 isolates are not always associated with more severe
      disease, even though they may produce larger amounts of toxins. Our study also
      suggests that current assertions regarding the NAP1/027 may not apply to all
      isolates and that other factors may come into play.

PMID- 21956986
TI  - An enhanced DNA fingerprinting service to investigate potential Clostridium
      difficile infection case clusters sharing the same PCR ribotype.
AB  - Of 53 potential Clostridium difficile infection (CDI) case clusters/outbreaks,
      affecting 2 to 41 patients in 27 institutions, 19% comprised unrelated isolates
      and 34% had highly related and distinct isolates as shown by multilocus variable
      number tandem-repeat analysis, despite sharing a common ribotype. These findings
      emphasize the value of enhanced fingerprinting to confirm or refute suspected CDI
      case clusters.

PMID- 21956987
TI  - Use of dried-blood-spot samples and in-house assays to identify antiretroviral
      drug resistance in HIV-infected children in resource-constrained settings.
AB  - Monitoring HIV drug resistance is an important component of the World Health
      Organization's global HIV program. HIV drug resistance testing is optimal with
      commercially available clinically validated test kits using plasma; however, that
      type of testing may not be feasible or affordable in resource-constrained
      settings. HIV genotyping from dried blood spots (DBS) with noncommercial (in
      house) assays may facilitate the capture of HIV drug resistance outcomes in
      resource-constrained settings but has had varying rates of success. With in-house
      assays for HIV reverse transcriptase, we evaluated the yield of genotyping DBS
      samples collected from HIV-infected children who were enrolled in two clinical
      trials conducted in sub-Saharan Africa (median HIV viral load, 5.88 log(10) HIV
      RNA copies/ml; range, 4.04 to 6.99). Overall, HIV genotypes were obtained for 94
      (89.5%) of 105 samples tested (95% and 84% from clinical trials #1 and #2,
      respectively); however, successful analysis of 15 (16.1%) of the 94 samples
      required repeat testing using a different set of primers on previously
      synthesized cDNA. The yield of genotyping was lower on the DBS that were stored
      suboptimally from clinical trial #2 (56% versus 88% for optimally stored).
      Concordance with plasma genotypes derived using a clinically validated,
      commercial kit-based assay (ViroSeq HIV-1 genotyping system) was also assessed in
      a subset of children with paired testing. For 34 samples with paired DBS and
      plasma genotypes, there was 100% concordance for major drug resistance mutations.
      DBS genotyping using in-house assays provides an alternative for antiretroviral
      drug resistance testing in children in resource-constrained regions but may
      require region-specific optimization before widespread use.

PMID- 21956988
TI  - Cyclospora papionis, Cryptosporidium hominis, and human-pathogenic Enterocytozoon
      bieneusi in captive baboons in Kenya.
AB  - Cyclospora papionis, Cryptosporidium hominis, and Enterocytozoon bieneusi were
      detected in 42 (17.9%), 6 (2.6%), and 29 (12.3%) of 235 newly captured baboons in
      Kenya, respectively. Most C. hominis subtypes and E. bieneusi genotypes found
      have been detected in humans in the area, suggesting that cross-species
      transmission of cryptosporidiosis and microsporidiosis is possible.

PMID- 21956989
TI  - Pandemic and seasonal human influenza virus infections in domestic cats:
      prevalence, association with respiratory disease, and seasonality patterns.
AB  - Domestic cats have several features that make them ideal vehicles for
      interspecies transmission of influenza viruses; however, they have been largely
      overlooked as potential reservoirs or bridging hosts. In this study, we conducted
      serological surveillance to assess the prevalence of novel pandemic H1N1 as well
      as seasonal human influenza virus infections in domestic cats in Ohio. Four
      hundred serum samples collected from domestic cats (September 2009 to September
      2010) were tested using a hemagglutination inhibition (HI) test. The
      seroprevalences of pandemic H1N1, seasonal H1N1, and H3N2 were 22.5%, 33%, and
      43.5%, respectively. In addition, a significant association between clinical
      feline respiratory disease and influenza virus infection was documented. In this
      sample of cats, the prevalence of pandemic H1N1 did not follow the seasonality
      pattern of seasonal H1N1 or H3N2 influenza, similar to observations in humans.
      Pandemic H1N1 seroprevalence did not vary in relation to ambient temperature
      changes, while the seroprevalence of seasonal H3N2 and H1N1 influenza viruses
      increased with the decline of ambient temperature. Our results highlight the high
      prevalence of influenza virus infection in domestic cats, a seasonality pattern
      of influenza virus infection comparable to that in humans, and an association of
      infection with clinical respiratory disease.

PMID- 21956990
TI  - Evaluation of Chlamydia trachomatis and Neisseria gonorrhoeae detection in urine,
      endocervical, and vaginal specimens by a multiplexed isothermal thermophilic
      helicase-dependent amplification (tHDA) assay.
AB  - We have developed a new research assay that combines sequence-specific sample
      preparation and isothermal amplification for the detection of Chlamydia
      trachomatis and Neisseria gonorrhoeae infections. The assay targets both the omp
      gene and the cryptic plasmid of C. trachomatis and the multicopy opa gene of N.
      gonorrhoeae, which are amplified and detected in a single reaction. We evaluated
      the ability of the assay to detect C. trachomatis and N. gonorrhoeae infections
      in first-catch urine, swab, and liquid-based cytology samples. Total agreement
      between the new assay and APTIMA Combo 2 varied between 95.3% and 100%, depending
      on the sample type and target detected. Total agreement between the new assay and
      BD ProbeTec varied between 96.7% and 100%, depending on the sample type and
      target detected. The assay has a simple work flow, and endpoint results can be
      achieved in 3 h, including sample preparation. The assay described here was
      evaluated for research use and was compared to commercially available assays.

PMID- 21956991
TI  - Systematic survey of clonal complexity in tuberculosis at a populational level
      and detailed characterization of the isolates involved.
AB  - Clonally complex infections by Mycobacterium tuberculosis are progressively more
      accepted. Studies of their dimension in epidemiological scenarios where the
      infective pressure is not high are scarce. Our study systematically searched for
      clonally complex infections (mixed infections by more than one strain and
      simultaneous presence of clonal variants) by applying mycobacterial interspersed
      repetitive-unit (MIRU)-variable-number tandem-repeat (VNTR) analysis to M.
      tuberculosis isolates from two population-based samples of respiratory (703
      cases) and respiratory-extrapulmonary (R+E) tuberculosis (TB) cases (71 cases) in
      a context of moderate TB incidence. Clonally complex infections were found in 11
      (1.6%) of the respiratory TB cases and in 10 (14.1%) of those with R+E TB. Among
      the 21 cases with clonally complex TB, 9 were infected by 2 independent strains
      and the remaining 12 showed the simultaneous presence of 2 to 3 clonal variants.
      For the 10 R+E TB cases with clonally complex infections, compartmentalization
      (different compositions of strains/clonal variants in independent infected sites)
      was found in 9 of them. All the strains/clonal variants were also genotyped by
      IS6110-based restriction fragment length polymorphism analysis, which split two
      MIRU-defined clonal variants, although in general, it showed a lower
      discriminatory power to identify the clonal heterogeneity revealed by MIRU-VNTR
      analysis. The comparative analysis of IS6110 insertion sites between coinfecting
      clonal variants showed differences in the genes coding for a cutinase, a PPE
      family protein, and two conserved hypothetical proteins. Diagnostic delay,
      existence of previous TB, risk for overexposure, and clustered/orphan status of
      the involved strains were analyzed to propose possible explanations for the cases
      with clonally complex infections. Our study characterizes in detail all the
      clonally complex infections by M. tuberculosis found in a systematic survey and
      contributes to the characterization that these phenomena can be found to an
      extent higher than expected, even in an unselected population-based sample
      lacking high infective pressure.

PMID- 21956992
TI  - Differing Neisseria gonorrhoeae bacterial loads in the pharynx and rectum in men
      who have sex with men: implications for gonococcal detection, transmission, and
      control.
AB  - The bacterial loads for gonococcal infections of the pharynx and rectum were
      determined among men with male sexual partners. The median bacterial load for
      rectal infections (18,960 copies/swab) was significantly higher than the load for
      pharyngeal infections (2,100 copies/swab; P = 0.001). Bacterial loads among men
      with symptomatic proctitis were strikingly high (median, 278,000 copies/swab).

PMID- 21956993
TI  - Positive predictive value of Leeds acinetobacter medium for environmental
      surveillance of Acinetobacter baumannii.

PMID- 21956994
TI  - Structural and electronic study of an amorphous MoS3 hydrogen-generation catalyst
      on a quantum-controlled photosensitizer.

PMID- 21956995
TI  - Two-phase analysis of molecular pathways underlying induced pluripotent stem cell
      induction.
AB  - Induced pluripotent stem cells (iPSCs) can be reprogrammed from adult somatic
      cells by transduction with Oct4, Sox2, Klf4, and c-Myc, but the molecular
      cascades initiated by these factors remain poorly understood. Impeding their
      elucidation is the stochastic nature of the iPS induction process, which results
      in heterogeneous cell populations. Here we have synchronized the reprogramming
      process by a two-phase induction: an initial stable intermediate phase following
      transduction with Oct4, Klf4, and c-Myc, and a final iPS phase following
      overexpression of Sox2. This approach has enabled us to examine temporal gene
      expression profiles, permitting the identification of Sox2 downstream genes
      critical for induction. Furthermore, we have validated the feasibility of our new
      approach by using it to confirm that downregulation of transforming growth factor
      beta signaling by Sox2 proves essential to the reprogramming process. Thus, we
      present a novel means for dissecting the details underlying the induction of
      iPSCs, an approach with significant utility in this arena and the potential for
      wide-ranging implications in the study of other reprogramming mechanisms.

PMID- 21956997
TI  - Clinical Biophotonics.

PMID- 21956998
TI  - Light-guided lumpectomy: first clinical experience.
AB  - Despite numerous advances, lumpectomy remains a challenging procedure. We report
      on the early use of light-guided lumpectomy. Eight patients with non-palpable
      breast cancer undergoing lumpectomy for biopsy-proven and radiographically
      identifiable cancer were enrolled in the study. An optical wire was designed that
      incorporated a standard hook-wire with an optical fiber. The optical wire was
      placed in the same manner as a standard hook-wire. During light-guided
      lumpectomy, an eye-safe laser illuminated the optical wire and created a sphere
      of light surrounding the cancer. The light was visible at the beginning of each
      surgery and facilitated approaching the cancer without using the wire. Dissection
      around the sphere of light kept the wire tip within the surgical specimen. Three
      of eight initial surgical specimens had focally positive margins. Additional
      cavity shaves were performed during five lumpectomies and resulted in negative
      margins in seven of eight patients. Light-guided lumpectomy is a minor change to
      breast conserving surgery that can be easily incorporated into clinical practice.
      Further investigation into the clinical benefit of light-guided lumpectomy is
      warranted.

PMID- 21957001
TI  - Single-walled nanotube/amphiphile hybrids for efficacious protein delivery:
      rational modification of dispersing agents.

PMID- 21957002
TI  - Genetic and environmental influences on growth from late childhood to adulthood:
      a longitudinal study of two Finnish twin cohorts.
AB  - OBJECTIVES: Human growth is a complex process that remains insufficiently
      understood. We aimed to analyze genetic and environmental influences on growth
      from late childhood to early adulthood. METHODS: Two cohorts of monozygotic and
      dizygotic (same sex and opposite sex) Finnish twin pairs were studied
      longitudinally using self-reported height at 11-12, 14, and 17 years and adult
      age (FinnTwin12) and at 16, 17, and 18 years and adult age (FinnTwin16).
      Univariate and multivariate variance component models for twin data were used.
      RESULTS: From childhood to adulthood, genetic differences explained 72-81% of the
      variation of height in boys and 65-86% in girls. Environmental factors common to
      co-twins explained 5-23% of the variation of height, with the residual variation
      explained by environmental factors unique to each twin individual. Common
      environmental factors affecting height were highly correlated between the
      analyzed ages (0.72-0.99 and 0.91-1.00 for boys and girls, respectively). Genetic
      (0.58-0.99 and 0.70-0.99, respectively) and unique environmental factors (0.32
      0.78 and 0.54-0.82, respectively) affecting height at different ages were more
      weakly, but still substantially, correlated. CONCLUSIONS: The genetic
      contribution to height is strong during adolescence. The high genetic
      correlations detected across the ages encourage further efforts to identify genes
      affecting growth. Common and unique environmental factors affecting height during
      adolescence are also important, and further studies are necessary to identify
      their nature and test whether they interact with genetic factors.

PMID- 21957003
TI  - Surface functionalization of silver nanoparticles: novel applications for insect
      vector control.
AB  - Every day, people and animals contract debilitating and life threatening diseases
      due to bites from infected flies, ticks, and mosquitoes. The current methods
      utilized to fight against these diseases are only partially effective or safe for
      humans and animals. When it comes to insect vector control, a conceptual paradigm
      shift is urgently needed. This work proposes a novel synthetic scheme to produce
      a nanoparticle-pesticide core-shell conjugate to be used as an active agent
      against arthropod vectors, such as mosquitoes. As a proof of concept, we
      conjugated nanosilver to the pyrethroid pesticide deltamethrin. First, electron
      microscopy and Fourier transform infrared spectroscopy verified the presence of a
      15 nm nanosilver core surrounded by deltamethrin. Second, when the conjugate was
      exposed to mosquitoes for a 24 h bioassay, mortality was observed at 9 * 10(-4)
      M. Silver was detected in the hemolymph of mosquitoes exposed to the conjugate.
      We concluded that the newly developed nanoconjugate did not inactivate the
      primary function of the pesticide and was effective in killing mosquitoes at low
      concentrations. These results demonstrate the potential to use nanoparticle
      surfaces to kill insects, specifically vectors of human pathogens.

PMID- 21957005
TI  - The RNA capping machinery as an anti-infective target.
AB  - A number of different human pathogens code for their own enzymes involved in the
      synthesis of the RNA cap structure. Although the RNA cap structures originating
      from human and microbial enzymes are often identical, the subunit composition,
      structure and catalytic mechanisms of the microbial-encoded enzymes involved in
      the synthesis of the RNA cap structure are often significantly different from
      those of host cells. As a consequence, these pathogenic cap-forming enzymes are
      potential targets for antimicrobial drugs. During the past few years,
      experimental studies have started to demonstrate that inhibition of the RNA
      capping activity is a reasonable approach for the development of antimicrobial
      agents. The combination of structural, biochemical, and molecular modeling
      studies are starting to reveal novel molecules that can serve as starting blocks
      for the design of more potent and specific antimicrobial agents. Here, we examine
      various strategies that have been developed to inhibit microbial enzymes involved
      in the synthesis of the RNA cap structure, emphasizing the challenges remaining
      to design potent and selective drugs.

PMID- 21957006
TI  - Structural and functional insights into eukaryotic mRNA decapping.
AB  - The control of messenger RNA (mRNA) translation and degradation is important in
      regulation of eukaryotic gene expression. In the general and specialized mRNA
      decay pathways which involve 5(') ->3(') decay, decapping is the central step
      because it is the controlling gate preceding the actual degradation of mRNA and
      is a site of numerous control inputs. Removal of the cap structure is catalyzed
      by a decapping holoenzyme composed of the catalytic Dcp2 subunit and the
      coactivator Dcp1. Decapping is regulated by decapping activators and inhibitors.
      Recent structural and kinetics studies indicated that Dcp1 and the substrate RNA
      promote the closed form of the enzyme and the catalytic step of decapping is rate
      limiting and accelerated by Dcp1. The conformational change between the open and
      closed decapping enzyme is important for controlling decapping, and regulation of
      this transition has been proposed to be a checkpoint for determining the fate of
      mRNAs. Here we summarize the past and recent advances on the structural and
      functional studies of protein factors involved in regulating mRNA decapping.

PMID- 21957004
TI  - Mechanisms of deadenylation-dependent decay.
AB  - Degradation of messenger RNAs (mRNAs) plays an essential role in modulation of
      gene expression and in quality control of mRNA biogenesis. Nearly all major mRNA
      decay pathways characterized thus far in eukaryotes are initiated by
      deadenylation, i.e., shortening of the mRNA 3(') poly(A) tail. Deadenylation is
      often a rate-limiting step for mRNA degradation and translational silencing,
      making it an important control point for both processes. In this review, we
      discuss the fundamental principles that govern mRNA deadenylation in eukaryotes.
      We use several major mRNA decay pathways in mammalian cells to illustrate
      mechanisms and regulation of deadenylation-dependent mRNA decay, including decay
      directed by adenine/uridine-rich elements (AREs) in the 3(') -untranslated region
      (UTR), the rapid decay mediated by destabilizing elements in protein-coding
      regions, the surveillance mechanism that detects and degrades nonsense-containing
      mRNA [i.e., nonsense-mediated decay (NMD)], the decay directed by miRNAs, and the
      default decay pathway for stable messages. Mammalian mRNA deadenylation involves
      two consecutive phases mediated by the PAN2-PAN3 and the CCR4-CAF1 complexes,
      respectively. Decapping takes place after deadenylation and may serve as a backup
      mechanism to trigger mRNA decay if initial deadenylation is compromised. In
      addition, we discuss how deadenylation impacts the dynamics of RNA processing
      bodies (P-bodies), where nontranslatable mRNAs can be degraded or stored.
      Possible models for mechanisms of various deadenylation-dependent mRNA decay
      pathways are also discussed.

PMID- 21957007
TI  - Antibiotics that target protein synthesis.
AB  - The key role of the bacterial ribosome makes it an important target for
      antibacterial agents. Indeed, a large number of clinically useful antibiotics
      target this complex translational ribonucleoprotein machinery. The majority of
      these compounds, mostly of natural origin, bind to one of the three key ribosomal
      sites: the decoding (or A-site) on the 30S, the peptidyl transferase center (PTC)
      on the 50S, and the peptide exit tunnel on the 50S. Antibiotics that bind the A
      site, such as the aminoglycosides, interfere with codon recognition and
      translocation. Peptide bond formation is inhibited when small molecules like
      oxazolidinones bind at the PTC. Finally, macrolides tend to block the growth of
      the amino acid chain at the peptide exit tunnel. In this article, the major
      classes of antibiotics that target the bacterial ribosome are discussed and
      classified according to their respective target. Notably, most antibiotics solely
      interact with the RNA components of the bacterial ribosome. The surge seen in the
      appearance of resistant bacteria has not been met by a parallel development of
      effective and broad-spectrum new antibiotics, as evident by the introduction of
      only two novel classes of antibiotics, the oxazolidinones and lipopeptides, in
      the past decades. Nevertheless, this significant health threat has revitalized
      the search for new antibacterial agents and novel targets. High resolution
      structural data of many ribosome-bound antibiotics provide unprecedented insight
      into their molecular contacts and mode of action and inspire the design and
      synthesis of new candidate drugs that target this fascinating molecular machine.

PMID- 21957008
TI  - The tmRNA-tagging mechanism and the control of gene expression: a review.
AB  - The tmRNA-mediated trans-translation system is a unique quality control system in
      eubacteria that combines translational surveillance with the rescue of stalled
      ribosomes. During trans-translation, the chimeric tmRNA molecule--which acts as
      both tRNA and mRNA--is delivered to the ribosomal A site by a ribonucleoprotein
      complex of SmpB and EF-Tu-GTP, allowing the stalled ribosome to switch template
      and resume translation on a small coding sequence inside the tmRNA molecule. As a
      result, the aberrant protein becomes tagged by a sequence that is a target for
      proteolytic degradation. Thus, the system elegantly combines ribosome recycling
      with a clean-up function when triggered by truncated transcripts or rare codons.
      In addition, recent observations point to a specific regulation of the
      translation of a small number of genes by tmRNA-mediated inhibition or
      stimulation. In this review, we discuss the most prominent biochemical and
      structural aspects of trans-translation and then focus on the specific role of
      tmRNA in stress management and cell-cycle control of morphologically complex
      bacteria.

PMID- 21957009
TI  - 3' processing in protists.
AB  - Molecular biologists have traditionally focused on the very small corner of
      eukaryotic evolution that includes yeast and animals; even plants have been
      neglected. In this article, we describe the scant information that is available
      concerning RNA processing in the other four major eukaryotic groups, especially
      pathogenic protists. We focus mainly on polyadenylation and nuclear processing of
      stable RNAs. These processes have--where examined--been shown to be conserved,
      but there are many novel details. We also briefly mention other processing
      reactions such as splicing.

PMID- 21957010
TI  - Cap and cap-binding proteins in the control of gene expression.
AB  - The 5' mRNA cap structure is essential for efficient gene expression from yeast
      to human. It plays a critical role in all aspects of the life cycle of an mRNA
      molecule. Capping occurs co-transcriptionally on the nascent pre-mRNA as it
      emerges from the RNA exit channel of RNA polymerase II. The cap structure
      protects mRNAs from degradation by exonucleases and promotes transcription,
      polyadenylation, splicing, and nuclear export of mRNA and U-rich, capped snRNAs.
      In addition, the cap structure is required for the optimal translation of the
      vast majority of cellular mRNAs, and it also plays a prominent role in the
      expression of eukaryotic, viral, and parasite mRNAs. Cap-binding proteins
      specifically bind to the cap structure and mediate its functions in the cell. Two
      major cellular cap-binding proteins have been described to date: eukaryotic
      translation initiation factor 4E (eIF4E) in the cytoplasm and nuclear cap binding
      complex (nCBC), a nuclear complex consisting of a cap-binding subunit cap-binding
      protein 20 (CBP 20) and an auxiliary protein cap-binding protein 80 (CBP 80).
      nCBC plays an important role in various aspects of nuclear mRNA metabolism such
      as pre-mRNA splicing and nuclear export, whereas eIF4E acts primarily as a
      facilitator of mRNA translation. In this review, we highlight recent findings on
      the role of the cap structure and cap-binding proteins in the regulation of gene
      expression. We also describe emerging regulatory pathways that control mRNA
      capping and cap-binding proteins in the cell.

PMID- 21957011
TI  - Recognition of S-adenosylmethionine by riboswitches.
AB  - Riboswitches are regulatory elements commonly found in the 5' leader sequences of
      bacterial mRNAs that bind cellular metabolites to direct expression at either the
      transcriptional or translational level. The effectors of these RNAs are
      chemically diverse, including nucleobases and nucleosides, amino acids,
      cofactors, and second messenger molecules. Over the last few years, a number of
      structures have revealed the architectural means by which RNA creates binding
      pockets of high affinity and specificity for these compounds. For most effectors,
      there is a single class of associated riboswitches. However, eight individual
      classes of S-adenosylmethionine (SAM) and/or S-adenosylhomocysteine (SAH)
      responsive riboswitches that control various aspects of sulfur metabolism have
      been validated, revealing a diverse set of solutions to the recognition of these
      ubiquitous metabolites. This review focuses upon the structures of RNAs that bind
      SAM and SAH and how they discriminate between these compounds.

PMID- 21957012
TI  - Animal clocks: a multitude of molecular mechanisms for circadian timekeeping.
AB  - Studies in various model organisms reveal that the expression level of a
      substantial part of the transcriptome and the proteome exhibits regular daily
      oscillations. These oscillations are translated to physiological and behavioral
      rhythms allowing organisms to efficiently anticipate and respond to the daily and
      seasonally changing environment (e.g., temperature and light). A rather small
      subset of evolutionary conserved genes drives these oscillations and constitutes
      the core molecular circadian clock. Here, we review the multiple mechanisms that
      coexist at various molecular and cellular levels and are involved in the metazoan
      circadian clock, including transcription/translation negative feedback loops,
      post-transcriptional and post-translational modifications, intracellular
      translocation, and intercellular signaling.

PMID- 21957013
TI  - Genetic studies of the cystathionine beta-synthase gene and myelomeningocele.
AB  - BACKGROUND: Among infants born with spina bifida, the most common defect is
      myelomeningocele (MM). The prevention of MM by maternal periconceptional folic
      acid (FA) supplementation has been studied extensively. The protective effect
      provided by FA suggests that the genes involved in folate metabolism, such as
      cystathionine beta-synthase (CBS), warrant further investigation. METHODS: This
      study sequenced the DNA from 96 patients with MM to identify novel potential
      disease-causing variants across the 17 exons of the CBS gene. The frequencies of
      known single nucleotide polymorphisms (SNPs) were identified, and sequences that
      differed from the reference sequences were considered novel variants. Statistical
      analysis was performed using two-sided Fisher's exact test to compare frequencies
      of SNPs between groups of patients and the known population frequencies. RESULTS:
      We found a new variant in exon 3 in one patient that results in a G/A change
      subsequently encoding a stop codon. In addition, we found a new variant in the 3'
      UTR of exon 17. Allele frequencies for 10 known single nucleotide polymorphisms
      (SNPs) were determined: rs234706, rs72058776, rs1801181, rs6582281, rs71872941,
      rs12613, rs706208, rs706209, rs73906420, and rs9982921. Of the remaining 48 known
      SNPs, all tested DNAs were homozygous for the major allele. CONCLUSION: We
      identified a previously undescribed variant in exon 3 that encodes a stop codon,
      thus halting downstream translation of the CBS protein. According to the Human
      Splicing Finder, the 3'-UTR variant found in exon 17 is predicted to abolish the
      recognition sites for two splice binding factors, SRp40 and SF2/ASF. The
      functional significance of the 3'-UTR mutation needs to be investigated.

PMID- 21957014
TI  - From model to crop: functional analysis of a STAY-GREEN gene in the model legume
      Medicago truncatula and effective use of the gene for alfalfa improvement.
AB  - Medicago truncatula has been developed into a model legume. Its close relative
      alfalfa (Medicago sativa) is the most widely grown forage legume crop in the
      United States. By screening a large population of M. truncatula mutants tagged
      with the transposable element of tobacco (Nicotiana tabacum) cell type1 (Tnt1),
      we identified a mutant line (NF2089) that maintained green leaves and showed
      green anthers, central carpels, mature pods, and seeds during senescence. Genetic
      and molecular analyses revealed that the mutation was caused by Tnt1 insertion in
      a STAY-GREEN (MtSGR) gene. Transcript profiling analysis of the mutant showed
      that loss of the MtSGR function affected the expression of a large number of
      genes involved in different biological processes. Further analyses revealed that
      SGR is implicated in nodule development and senescence. MtSGR expression was
      detected across all nodule developmental zones and was higher in the senescence
      zone. The number of young nodules on the mutant roots was higher than in the wild
      type. Expression levels of several nodule senescence markers were reduced in the
      sgr mutant. Based on the MtSGR sequence, an alfalfa SGR gene (MsSGR) was cloned,
      and transgenic alfalfa lines were produced by RNA interference. Silencing of
      MsSGR led to the production of stay-green transgenic alfalfa. This beneficial
      trait offers the opportunity to produce premium alfalfa hay with a more greenish
      appearance. In addition, most of the transgenic alfalfa lines retained more than
      50% of chlorophylls during senescence and had increased crude protein content.
      This study illustrates the effective use of knowledge gained from a model system
      for the genetic improvement of an important commercial crop.

PMID- 21957015
TI  - Segmental isotopic labeling of ubiquitin chains to unravel monomer-specific
      molecular behavior.

PMID- 21957016
TI  - MEK-ERK signaling dictates DNA-repair gene MGMT expression and temozolomide
      resistance of stem-like glioblastoma cells via the MDM2-p53 axis.
AB  - Overcoming the resistance of glioblastoma cells against temozolomide, the first
      line chemotherapeutic agent of choice for newly diagnosed glioblastoma, is a
      major therapeutic challenge in the management of this deadly brain tumor. The
      gene encoding O(6) -methylguanine DNA methyltransferase (MGMT), which removes the
      methyl group attached by temozolomide, is often silenced by promoter methylation
      in glioblastoma but is nevertheless expressed in a significant fraction of cases
      and is therefore regarded as one of the most clinically relevant mechanisms of
      resistance against temozolomide. However, to date, signaling pathways regulating
      MGMT in MGMT-expressing glioblastoma cells have been poorly delineated. Here in
      this study, we provide lines of evidence that the mitogen-activated
      protein/extracellular signal-regulated kinase kinase (MEK)-extracellular signal
      regulated kinase (ERK)-murine double minute 2 (MDM2)-p53 pathway plays a critical
      role in the regulation of MGMT expression, using stem-like glioblastoma cells
      directly derived from patient tumor samples and maintained in the absence of
      serum, which not only possess stem-like properties but are also known to
      phenocopy the characteristics of the original tumors from which they are derived.
      We show that, in stem-like glioblastoma cells, MEK inhibition reduced MDM2
      expression and that inhibition of either MEK or MDM2 resulted in p53 activation
      accompanied by p53-dependent downregulation of MGMT expression. MEK inhibition
      rendered otherwise resistant stem-like glioblastoma cells sensitive to
      temozolomide, and combination of MEK inhibitor and temozolomide treatments
      effectively deprived stem-like glioblastoma cells of their tumorigenic potential.
      Our findings suggest that targeting of the MEK-ERK-MDM2-p53 pathway in
      combination with temozolomide could be a novel and promising therapeutic strategy
      in the treatment of glioblastoma.

PMID- 21957017
TI  - Titania photocatalysts for selective oxidations in water.

PMID- 21957018
TI  - Alu polymorphisms in the Waorani tribe from the Ecuadorian Amazon reflect the
      effects of isolation and genetic drift.
AB  - OBJECTIVES: The Amazon basin is inhabited by some of the most isolated human
      groups worldwide. Among them, the Waorani tribe is one of the most interesting
      Native American populations from the anthropological perspective. This study
      reports a genetic characterization of the Waorani based on autosomal genetic
      loci. METHODS: We analyzed 12 polymorphic Alu insertions in 36 Waorani
      individuals from different communal longhouses settled in the Yasuni National
      Park. RESULTS: The most notable finding was the strikingly reduced genetic
      diversity detected in the Waorani, corroborated by the existence of four
      monomorphic loci (ACE, APO, FXIIIB, and HS4.65), and of other four Alu markers
      that were very close to the fixation for the presence (PV92 and D1) or the
      absence (A25 and HS4.32) of the insertion. Furthermore, results of the centroid
      analysis supported the notion of the Waorani being one of the Amerindian groups
      less impacted by gene flow processes. CONCLUSIONS: The prolonged isolation of the
      Waorani community, in conjunction with a historically low effective population
      size and high inbreeding levels, have resulted in the drastic reduction of their
      genetic diversity, because of the effects of severe genetic drift. Recurrent
      population bottlenecks most likely determined by certain deep-rooted
      sociocultural practices of the Waorani (characterized by violence, internal
      quarrels, and revenge killings until recent times) are likely responsible for
      this pattern of diversity. The findings of this study illustrate how
      sociocultural factors can shape the gene pool of human populations.

PMID- 21957021
TI  - Turnover of AU-rich-containing mRNAs during stress: a matter of survival.
AB  - Cells undergo various adaptive measures in response to stress. Among these are
      specific changes in the posttranscriptional regulation of various genes. In
      particular, the turnover of mRNA is modified to either increase or decrease the
      abundance of certain target messages. Some of the best-studied mRNAs that are
      affected by stress are those that contain adenine/uridine-rich elements (AREs) in
      their 3'-untranslated regions. ARE-containing mRNAs are involved in many
      important cellular processes and are normally labile, but in response to stress
      they are differentially regulated through the concerted efforts of ARE-binding
      proteins (AUBPs) such as HuR, AUF1, tristetraprolin, BRF1, and KSRP, along with
      microRNA-mediated effects. Additionally, the fate of ARE-containing mRNAs is
      modified by inducing their localization to stress granules or mRNA processing
      bodies. Coordination of these various mechanisms controls the turnover of ARE
      containing mRNAs, and thereby enables proper responses to cellular stress. In
      this review, we discuss how AUBPs regulate their target mRNAs in response to
      stress, along with the involvement of cytoplasmic granules in this process.

PMID- 21957020
TI  - Pre-mRNA 3'-end processing complex assembly and function.
AB  - The 3'-ends of almost all eukaryotic mRNAs are formed in a two-step process, an
      endonucleolytic cleavage followed by polyadenylation (the addition of a poly
      adenosine or poly(A) tail). These reactions take place in the pre-mRNA 3'
      processing complex, a macromolecular machinery that consists of more than 20
      proteins. A general framework for how the pre-mRNA 3' processing complex
      assembles and functions has emerged from extensive studies over the past several
      decades using biochemical, genetic, computational, and structural approaches. In
      this article, we review what we have learned about this important cellular
      machine and discuss the remaining questions and future challenges.

PMID- 21957022
TI  - Control of poly(A) tail length.
AB  - Poly(A) tails have long been known as stable 3' modifications of eukaryotic
      mRNAs, added during nuclear pre-mRNA processing. It is now appreciated that this
      modification is much more diverse: A whole new family of poly(A) polymerases has
      been discovered, and poly(A) tails occur as transient destabilizing additions to
      a wide range of different RNA substrates. We review the field from the
      perspective of poly(A) tail length. Length control is important because (1)
      poly(A) tail shortening from a defined starting point acts as a timer of mRNA
      stability, (2) changes in poly(A) tail length are used for the purpose of
      translational regulation, and (3) length may be the key feature distinguishing
      between the stabilizing poly(A) tails of mRNAs and the destabilizing oligo(A)
      tails of different unstable RNAs. The mechanism of length control during nuclear
      processing of pre-mRNAs is relatively well understood and is based on the changes
      in the processivity of poly(A) polymerase induced by two RNA-binding proteins.
      Developmentally regulated poly(A) tail extension also generates defined tails;
      however, although many of the proteins responsible are known, the reaction is not
      understood mechanistically. Finally, destabilizing oligoadenylation does not
      appear to have inherent length control. Rather, average tail length results from
      the balance between polyadenylation and deadenylation.

PMID- 21957023
TI  - Human mitochondrial diseases caused by lack of taurine modification in
      mitochondrial tRNAs.
AB  - Mitochondrial DNA mutations that cause mitochondrial dysfunction are responsible
      for a wide spectrum of human diseases, referred to as mitochondrial diseases.
      Pathogenic point mutations are found frequently in genes encoding mitochondrial
      (mt) tRNAs, indicating that impaired functioning of mutant mt tRNAs is the
      primary cause of mitochondrial dysfunction. Our previous studies revealed the
      absence of posttranscriptional taurine modification at the anticodon wobble
      uridine in mutant mt tRNAs isolated from cells derived from patients with two
      major classes of mitochondrial diseases, MELAS (mitochondrial myopathy,
      encephalopathy, lactic acidosis, and stroke-like episodes) and MERRF (myoclonus
      epilepsy associated with ragged red fibers). Defective taurine modification of
      the mutant mt tRNAs results in a deficiency in protein synthesis as the cognate
      codons of the mutant mt tRNA cannot be decoded. These findings represent the
      first evidence of a molecular pathogenesis caused by an RNA modification
      disorder.

PMID- 21957024
TI  - Bacillus subtilis mRNA decay: new parts in the toolkit.
AB  - Representatives of two new ribonuclease families have recently been discovered in
      the gram-positive model organism, Bacillus subtilis. The RNase J family founding
      members, RNase J1 and RNase J2, are highly homologous but show differential
      activities. Although both are broad-specificity endonucleases, only the essential
      RNase J1 is a 5' -> 3' exonuclease-a type of ribonuclease activity that was
      previously thought not to exist in bacteria. Current data suggest that RNase J1
      is highly involved in the turnover of mRNA decay intermediates and may also be
      involved in the initiation of mRNA decay. A second family of ribonucleases is
      represented by RNase Y, an endonuclease that exerts a large effect on global mRNA
      half-life. The presence of these ribonucleases in B. subtilis predicts
      significant differences from the well-established model of mRNA decay in
      Escherichia coli.

PMID- 21957025
TI  - The structural landscape of native editosomes in African trypanosomes.
AB  - The majority of mitochondrial pre-messenger RNAs in African trypanosomes are
      substrates of a U-nucleotide-specific insertion/deletion-type RNA editing
      reaction. The process converts nonfunctional pre-mRNAs into translation-competent
      molecules and can generate protein diversity by alternative editing. High
      molecular mass protein complexes termed editosomes catalyze the processing
      reaction. They stably interact with pre-edited mRNAs and small noncoding RNAs,
      known as guide RNAs (gRNAs), which act as templates in the reaction. Editosomes
      provide a molecular surface for the individual steps of the catalytic reaction
      cycle and although the protein inventory of the complexes has been studied in
      detail, a structural analysis of the processing machinery has only recently been
      accomplished. Electron microscopy in combination with single particle
      reconstruction techniques has shown that steady state isolates of editosomes
      contain ensembles of two classes of stable complexes with calculated apparent
      hydrodynamic sizes of 20S and 35-40S. 20S editosomes are free of substrate RNAs,
      whereas 35-40S editosomes are associated with endogenous mRNA and gRNA molecules.
      Both complexes are characterized by a diverse structural landscape, which include
      complexes that lack or possess defined subdomains. Here, we summarize the
      consensus models and structural landmarks of both complexes. We correlate
      structural features with functional characteristics and provide an outlook into
      dynamic aspects of the editing reaction cycle.

PMID- 21957027
TI  - Trans-splicing.
AB  - Trans-splicing is the joining together of portions of two separate pre-mRNA
      molecules. The two distinct categories of spliceosomal trans-splicing are genic
      trans-splicing, which joins exons of different pre-mRNA transcripts, and spliced
      leader (SL) trans-splicing, which involves an exon donated from a specialized SL
      RNA. Both depend primarily on the same signals and components as cis-splicing.
      Genic trans-splicing events producing protein-coding mRNAs have been described in
      a variety of organisms, including Caenorhabditis elegans and Drosophila. In
      mammalian cells, genic trans-splicing can be associated with cancers and
      translocations. SL trans-splicing has mainly been studied in nematodes and
      trypanosomes, but there are now numerous and diverse phyla (including primitive
      chordates) where this type of trans-splicing has been detected. Such diversity
      raises questions as to the evolutionary origin of the process. Another intriguing
      question concerns the function of trans-splicing, as operon resolution can only
      account for a small proportion of the total amount of SL trans-splicing.

PMID- 21957026
TI  - Posttranscriptional regulation in Drosophila oocytes and early embryos.
AB  - Molecular asymmetries underlying embryonic axis patterning and germ cell
      specification are established in Drosophila largely by position-dependent
      translational regulation of maternally expressed messenger RNAs. Here, I review
      several mechanisms of posttranscriptional regulation in the Drosophila oocyte and
      syncytial embryo, and how they relate to embryonic patterning, with a strong
      emphasis on the most recent advances in the area. The review is not exhaustive,
      but focuses on examples that illustrate the interplay between specific regulatory
      events and the general metabolic machinery that governs translation and mRNA
      stability. Biophysical investigations into how the Bicoid gradient is formed are
      discussed, as are the elaborate mechanisms controlling how the Oskar and Nanos
      proteins become restricted to the posterior pole of the embryo. Work on Vasa, a
      translational activator of some germ line mRNAs and on 4EHP, a negative regulator
      that unproductively binds the 5' cap structure of target mRNAs, is also briefly
      reviewed. Finally, the emerging understanding of the role of microRNAs in
      regulating translation of germ line mRNAs is also discussed.

PMID- 21957028
TI  - HuR's role in gemcitabine efficacy: an exception or opportunity?
AB  - Over the next few years, research teams will focus on, and millions of dollars
      will be spent on, sorting through cancer genomes. Undoubtedly, 'druggable'
      targets and events will be discovered that will improve our understanding and,
      hopefully, treatment of cancer. Highlighting an alternative to this 'genome
      centric' approach, this review will further explore an underappreciated mechanism
      of gene expression regulation, posttranscription mRNA:protein interactions. A key
      molecule involved in this mode of gene regulation is HuR and we have shown that
      HuR levels and HuR cellular distribution can predict how pancreatic cancer
      patients responded to the standard of care chemotherapy (i.e., gemcitabine). HuR
      regulates post-transcriptional processes through: (1) association with specific
      mRNA cargos with ARE-rich sequences and (2) stress-induced increased cytoplasmic
      protein levels. Over multiple laboratories and diverse tumor types, it has been
      shown that HuR supports tumor survival through its regulation of tumor-promoting
      transcripts such as VEGF. In this article, we will highlight a recent discovery
      that this potent post-transcriptional gene regulatory mechanism has an impact on
      a common chemotherapeutic, gemcitabine. Specifically, we have identified the
      mechanism by which HuR can regulate a key gemcitabine metabolic enzyme,
      deoxycytidine kinase. We will use this example to explore and hypothesize the
      functional roles that HuR may have on anticancer drug therapies. We will survey
      novel high throughput global gene expression analysis tools to discover novel HuR
      targets. Future multidisciplinary approaches focused on HuR biology will provide
      critical events and 'druggable' targets in cancer that large-scale genomic
      sequencing efforts will miss.

PMID- 21957029
TI  - Alternative polyadenylation and gene expression regulation in plants.
AB  - Functioning as an essential step of pre-mRNA processing, polyadenylation has been
      realized in recent years to play an important regulatory role during eukaryotic
      gene expression. Such regulation occurs mostly through the use of alternative
      polyadenylation (APA) sites and generates different transcripts with altered
      coding capacity for proteins and/or RNA. However, the molecular mechanisms that
      underlie APAs are poorly understood. Besides APA cases demonstrated in animal
      embryo development, cancers, and other diseases, there are a number of APA
      examples reported in plants. The best-known ones are related to flowering time
      control pathways and stress responses. Genome-wide studies have revealed that
      plants use APA extensively to generate diversity in their transcriptomes.
      Although each transcript produced by RNA polymerase II has a poly(A) tail, over
      50% of plant genes studied possess multiple APA sites in their transcripts. The
      signals defining poly(A) sites in plants were mostly studied through classical
      genetic means. Our understanding of these poly(A) signals is enhanced by the
      tallies of whole plant transcriptomes. The profiles of these signals have been
      used to build computer models that can predict poly(A) sites in newly sequenced
      genomes, potential APA sites in genes of interest, and/or to identify, and then
      mutate, unwanted poly(A) sites in target transgenes to facilitate crop
      improvements. In this review, we provide readers an update on recent research
      advances that shed light on the understanding of polyadenylation, APA, and its
      role in gene expression regulation in plants.

PMID- 21957030
TI  - Internet guidance in oncology practice: determinants of health professionals'
      Internet referral behavior.
AB  - BACKGROUND: Many cancer patients turn to the Internet to obtain information on
      their disease. This digital quest is often motivated by a perceived discrepancy
      between the information received from health professionals and patients' actual
      informational needs. This discrepancy may be reduced by supplementing standard
      patient education with reliable online information sources. This study
      investigates health professionals' opinions, cognitions, and behavior regarding
      referring cancer patients to Internet-based information. METHODS: Online and
      written questionnaires were distributed among Dutch oncology nurses and medical
      specialists, measuring perception of patients' informational needs, prompted and
      unprompted Internet referral, and socio-cognitive factors regarding referral
      behavior. RESULTS: Health professionals (N = 130) positively appraised Internet
      use among cancer patients. Despite recognizing patients' needs for additional
      information (84%) and need for referral to reliable websites (67%), only 20%
      frequently referred patients to Internet-based information. Prompted Internet
      referral was higher (64%). Motives for nonreferral included unfamiliarity with
      websites and uncertainty about information quality. Intentions towards future
      referral were moderate to high. To translate intentions into referral, health
      professionals need reminder tools and information on reliability and content of
      websites. Cognitive determinants of referral behavior included professionals'
      attitude, self-efficacy, and intentions regarding referral. CONCLUSIONS:
      Recognition of patients' information needs does not culminate in Internet
      referral among health professionals in cancer care. High intentions to change,
      however, indicate good prospects for future referral. This study yields valuable
      insights into behavioral determinants of health professionals' Internet referral
      behavior. Targeting determinants and barriers in future interventions will
      provide opportunities for optimization of educational practices.

PMID- 21957031
TI  - Convenient and general palladium-catalyzed carbonylative Sonogashira coupling of
      aryl amines.

PMID- 21957032
TI  - Mechanisms of weight maintenance under high- and low-protein, low-glycaemic index
      diets.
AB  - SCOPE: Weight maintenance after intended weight loss is a challenge in an
      obesogenic environment. In a large multicentre dietary intervention study
      (DiOGenes), it has recently been demonstrated that a high-protein/low-glycaemic
      index (HP/LGI) diet was slightly more efficient in maintaining weight loss than
      low-protein/LGI or high-GI (LP/LGI or HGI) diets. Here, we use a proteomic
      approach to assess the molecular mechanisms behind this positive effect. METHODS
      AND RESULTS: A subset of the most successful (weight loser, n=12) and
      unsuccessful (weight re-gainer, n=12) individuals consuming the LGI diets with
      either high- or low-protein content (HP or LP/LGI), following an initial calorie
      deficit run-in weight loss phase, were analyzed at the plasma protein level.
      Proteomic analysis revealed 18 proteins regulated after 6 months of the dietary
      weight maintenance phase. Furthermore, 12 proteins were significantly regulated
      as a function of success rate under an HP diet, arising as candidate biomarkers
      of mechanisms of successful weight maintenance under an HP/LGI diet. Pregnancy
      zone protein (PZP) and protein S (PROS1) were revealed as novel biomarkers of
      weight maintenance showing opposite effects. CONCLUSION: Semantic network
      analysis of the 12 regulated proteins revealed that under an HP/LGI an anti
      atherogenic effect and alterations of fat metabolism were associated with the
      success of maintaining the initial weight loss.

PMID- 21957033
TI  - Brief report: L1 cell adhesion molecule, a novel surface molecule of human
      embryonic stem cells, is essential for self-renewal and pluripotency.
AB  - Despite the recent identification of surface markers of undifferentiated human
      embryonic stem cells (hESCs), the crucial cell-surface molecules that regulate
      the self-renewal capacity of hESCs remain largely undefined. Here, we generated
      monoclonal antibodies (MAbs) that specifically bind to undifferentiated hESCs but
      not to mouse embryonic stem cells. Among these antibodies, we selected a novel
      MAb, 4-63, and identified its target antigen as the L1 cell adhesion molecule
      (L1CAM) isoform 2. Notably, L1CAM expressed in hESCs lacked the neuron-specific
      YEGHH and RSLE peptides encoded by exons 2 and 27, respectively. L1CAM
      colocalized with hESC-specific cell-surface markers, and its expression was
      markedly downregulated on differentiation. Stable L1CAM depletion markedly
      decreased hESC proliferation, whereas L1CAM overexpression increased
      proliferation. In addition, the expression of octamer-binding transcription
      factor 4, Nanog, sex-determining region Y-box 2, and stage-specific embryonic
      antigen (SSEA)-3 was markedly downregulated, whereas lineage-specific markers and
      SSEA-1 were upregulated in L1CAM-depleted hESCs. Interestingly, the actions of
      L1CAM in regulating the proliferation and differentiation of hESCs were exerted
      predominantly through the fibroblast growth factor receptor 1 signaling pathway.
      Taken together, our results suggest that L1CAM is a novel cell-surface molecule
      that plays an important role in the maintenance of self-renewal and pluripotency
      in hESCs.

PMID- 21957035
TI  - In-between complex and cluster: a 14-vertex cage in [Ag2Se12]2+.

PMID- 21957034
TI  - The role of amine surface density in carbon dioxide adsorption on functionalized
      mixed oxide surfaces.
AB  - Supported amines are considered as adsorbents to replace aqueous amines for
      carbon capture and for CO(2) capture/conversion into chemicals. Here, amines are
      grafted to SiO(2) or Ti-SiO(2) by using aminopropyl triethoxysilane (APTES) or (3
      triethoxysilylpropyl)-tert-butylcarbamate (TESPtBC) and then removing the
      carbamate group introduced by the latter by mild heating to 'deprotect' the
      amine. Structures are verified by using (13) C cross polarization magic angle
      spinning (CP/MAS) NMR spectroscopy, acid titration, thermogravimetric analysis,
      and elemental analysis. Diffuse reflectance UV/Visible spectroscopy shows that
      amines from APTES coordinate directly to Ti cations, whereas Ti cations remain
      coordinatively unsaturated after grafting of TESPtBC and deprotection. CO(2)
      chemisorption is studied as a function of amine precursor, average surface
      density, and the presence of Ti. CO(2) uptake increases from <0.02 CO(2) per
      amine for as-synthesized TESPtBC materials to only approximately 0.05 CO(2) per
      amine for the isolated amines present after deprotection. In contrast, clustered
      amines from APTES chemisorb up to approximately 0.35 CO(2) per amine. Cooperative
      ammonium carbamates form preferentially above an apparent local density of 0.6
      amines per nm(2) from APTES, but do not form even up to 0.9 amines per nm(2) for
      TESPtBC-derived materials. This suggests that the true local surface density form
      APTES is underestimated by as much as 150 %. CO(2) uptake falls to <0.01 CO(2)
      per amine for ATPES on Ti?SiO(2), but uptake is less affected for the 'protected'
      TESPtBC precursor. These results show that TESPtBC may be a viable precursor for
      applications in acid-base cooperative CO(2) conversion catalysts, and that
      variation in the local amine surface density and the chemistry of the underlying
      support may account for some of the large variability in reported CO(2)
      capacities of supported amine materials in literature.

PMID- 21957036
TI  - Postnatal ontogeny of tibia and femur form in two human populations: a
      multivariate morphometric analysis.
AB  - OBJECTIVES: Adult population differences in relative and absolute limb size often
      are explained as adaptations to different climates. Less is known about other
      aspects of limb bone form and their population-specific growth patterns. METHODS:
      We study postnatal ontogenetic development of tibial and femoral form by a
      multivariate morphometric approach in a cross-sectional sample of South African
      (N = 97) and European (N = 81) modern humans from 0 to 20 years of age. Because
      the epiphyses ossify and fuse to the diaphysis in this time period, we separately
      analyze two sets of variables. Average ontogenetic trajectories are computed to
      compare the growth patterns of the African and the European groups. RESULTS: For
      both the tibia and the femur, we could show that Africans and Europeans have a
      very similar average length and average shape until about 10 years of age. During
      adolescence Africans have a higher growth rate leading to longer adult bones with
      narrower epiphyses relative to the diaphysis. Despite substantial individual
      overlap, the average crural index is higher in Africans than in Europeans, from
      birth on through adulthood. CONCLUSIONS: The prenatal origin of population
      differences in the crural index indicates a genetic determination of these
      differences whereas limb length and relative epiphyseal width likely are both
      genetically and environmentally determined.

PMID- 21957037
TI  - An active role for splicing in 3'-end formation.
AB  - When intron-defined splicing was replaced by exon-defined splicing in the
      evolution of higher eukaryotes, the splicing apparatus had to rely on the
      cleavage/polyadenylation (CP) apparatus for help in defining the 3'-terminal
      exon. The 3'-terminal exon-definition complex that resulted consists of splicing
      factors on the upstream 3' splice site (ss) interacting with CP factors on the
      downstream poly(A) signal. A speculative model for assembly of this processing
      complex proposes several discrete steps. First, the splicing factor, U2AF65,
      interacts with the CP factor, CFI(m). Then, CFI(m) is displaced from U2AF65 by
      the poly(A) polymerase during a remodeling step. Finally, the U2 snRNP interacts
      with CPSF in a step resembling spliceosomal A-complex formation. The result is
      mutual enhancement of both splicing and CP for the exon. In contrast, when the
      poly(A) signal is preceded by a 5' rather than a 3' ss, competition replaces
      cooperation. Thus, a poly(A) site in an intron must compete with the upstream 5'
      ss for pairing with the 3' ss further upstream, across the presumptive exon. If
      the poly(A) site wins the competition, a terminal exon is defined. But if the 5'
      ss wins (by defining the upstream exon as internal, followed by pairing with a 3'
      ss across the downstream intron), then the poly(A) site is suppressed. The U1
      snRNP obviously participates in this competition through its role in splice site
      pairing. However, the U1 snRNP can also bind elsewhere in the transcript, apart
      from splice sites, to regulate CP by direct interaction with the CP factors.

PMID- 21957038
TI  - Roles of Puf proteins in mRNA degradation and translation.
AB  - Puf proteins are regulators of diverse eukaryotic processes including stem cell
      maintenance, organelle biogenesis, oogenesis, neuron function, and memory
      formation. At the molecular level, Puf proteins promote translational repression
      and/or degradation of target mRNAs by first interacting with conserved cis
      elements in the 3' untranslated region (UTR). Once bound to an mRNA, Puf proteins
      elicit RNA repression by complex interactions with protein cofactors and
      regulatory machinery involved in translation and degradation. Recent work has
      dramatically increased our understanding of the targets of Puf protein
      regulation, as well as the mechanisms by which Puf proteins recognize and
      regulate those mRNA targets. Crystal structure analysis of several Puf-RNA
      complexes has demonstrated that while Puf proteins are extremely conserved in
      their RNA-binding domains, Pufs attain target specificity by utilizing different
      structural conformations to recognize 8-10 nt sequences. Puf proteins have also
      evolved modes of protein interactions that are organism and transcript-specific,
      yet two common mechanisms of repression have emerged: inhibition of cap-binding
      events to block translation initiation, and recruitment of the CCR4-POP2-NOT
      deadenylase complex for poly(A) tail removal. Finally, multiple schemes to
      regulate Puf protein activity have been identified, including post-translational
      mechanisms that allow rapid changes in the repression of mRNA targets.

PMID- 21957039
TI  - Organellar RNA editing.
AB  - RNA editing is a term used for a number of mechanistically different processes
      that alter the nucleotide sequence of RNA molecules to differ from the gene
      sequence. RNA editing occurs in a wide variety of organisms and is particularly
      frequent in organelle transcripts of eukaryotes. The discontiguous phylogenetic
      distribution of mRNA editing, the mechanistic differences observed in different
      organisms, and the nonhomologous editing machinery described in different
      taxonomic groups all suggest that RNA editing has appeared independently several
      times. This raises questions about the selection pressures acting to maintain
      editing that are yet to be completely resolved. Editing tends to be frequent in
      organisms with atypical organelle genomes and acts to correct the effect of DNA
      mutations that would otherwise compromise the synthesis of functional proteins.
      Additional functions of editing in generating protein diversity or regulating
      gene expression have been proposed but so far lack widespread experimental
      evidence, at least in organelles.

PMID- 21957040
TI  - Guarding the 'translation apparatus': defective ribosome biogenesis and the p53
      signaling pathway.
AB  - Ribosomes, the molecular factories that carry out protein synthesis, are
      essential for every living cell. Ribosome biogenesis, the process of ribosome
      synthesis, is highly complex and energy consuming. Over the last decade, many
      exciting and novel findings have linked various aspects of ribosome biogenesis to
      cell growth and cell cycle control. Defects in ribosome biogenesis have also been
      linked to human diseases. It is now clear that disruption of ribosome biogenesis
      causes nucleolar stress that triggers a p53 signaling pathway, thus providing
      cells with a surveillance mechanism for monitoring ribosomal integrity. Although
      the exact mechanisms of p53 induction in response to nucleolar stress are still
      unknown, several ribosomal proteins have been identified as key players in this
      ribosome-p53 signaling pathway. Recent studies of human ribosomal pathologies in
      a variety of animal models have also highlighted the role of this pathway in the
      pathophysiology of these diseases. However, it remains to be understood why the
      effect of ribosomal malfunction is not a universal response in all cell types but
      is restricted to particular tissues, causing the specific phenotypes seen in
      ribosomal diseases. A challenge for future studies will be to identify additional
      players in this signaling pathway and to elucidate the underlying molecular
      mechanisms that link defective ribosome synthesis to p53.

PMID- 21957041
TI  - Eukaryotic 5S rRNA biogenesis.
AB  - The ribosome is a large complex containing both protein and RNA which must be
      assembled in a precise manner to allow proper functioning in the critical role of
      protein synthesis. 5S rRNA is the smallest of the RNA components of the ribosome,
      and although it has been studied for decades, we still do not have a clear
      understanding of its function within the complex ribosome machine. It is the only
      RNA species that binds ribosomal proteins prior to its assembly into the
      ribosome. Its transport into the nucleolus requires this interaction. Here we
      present an overview of some of the key findings concerning the structure and
      function of 5S rRNA and how its association with specific proteins impacts its
      localization and function.

PMID- 21957042
TI  - Posttranscriptional control of X-chromosome dosage compensation.
AB  - RNA regulation plays a major role in the generation of diversity at the molecular
      and cellular levels, and furnishes the cell with flexibility potential to adapt
      to changing environments. Often, the regulation by/of RNA dictates when, where,
      and how the information encoded in the nucleus is revealed. One example is the
      regulation of X-chromosome dosage compensation. In Drosophila, differences in X
      linked gene dosage between males and females are compensated by the
      transcriptional upregulation of the single male X chromosome. Mechanisms of
      alternative splicing and translational control, among others, enforce dosage
      compensation in males while inhibiting this process in females. In this review,
      we discuss the posttranscriptional RNA regulatory mechanisms that ensure
      appropriate dosage compensation in Drosophila, drawing parallels with the
      mammalian system when appropriate.

PMID- 21957043
TI  - SMN in spinal muscular atrophy and snRNP biogenesis.
AB  - Ribonucleoprotein (RNP) complexes function in nearly every facet of cellular
      activity. The spliceosome is an essential RNP that accurately identifies introns
      and catalytically removes the intervening sequences, providing exquisite control
      of spatial, temporal, and developmental gene expressions. U-snRNPs are the
      building blocks for the spliceosome. A significant amount of insight into the
      molecular assembly of these essential particles has recently come from a
      seemingly unexpected area of research: neurodegeneration. Survival motor neuron
      (SMN) performs an essential role in the maturation of snRNPs, while the
      homozygous loss of SMN1 results in the development of spinal muscular atrophy
      (SMA), a devastating neurodegenerative disease. In this review, the function of
      SMN is examined within the context of snRNP biogenesis and evidence is examined
      which suggests that the SMN functional defects in snRNP biogenesis may account
      for the motor neuron pathology observed in SMA.

PMID- 21957044
TI  - Single-molecule direct RNA sequencing without cDNA synthesis.
AB  - Methods for in-depth genome-wide characterization of transcriptomes and
      quantification of transcript levels using various microarray and next-generation
      sequencing technologies have emerged as valuable tools for understanding cellular
      physiology and human disease biology and have begun to be utilized in various
      clinical diagnostic applications. Current methods, however, typically require RNA
      to be converted to complementary DNA prior to measurements. This step has been
      shown to introduce many biases and artifacts. In order to best characterize the
      'true' transcriptome, the single-molecule direct RNA sequencing (DRS) technology
      was developed. This review focuses on the underlying principles behind the DRS,
      sample preparation steps, and the current and novel avenues of research and
      applications DRS offers.

PMID- 21957045
TI  - Functions and mechanisms of spliceosomal small nuclear RNA pseudouridylation.
AB  - Pseudouridines are the most abundant and highly conserved modified nucleotides
      identified in spliceosomal small nuclear RNAs (snRNAs). Most pseudouridines are
      also clustered in functionally important regions of spliceosomal snRNAs.
      Experiments carried out in several independent experimental systems show that the
      pseudouridines in spliceosomal snRNAs are functionally important for pre
      messenger RNA (mRNA) splicing. Experimental data also indicate that spliceosomal
      snRNA pseudouridylation can be catalyzed by both RNA-dependent (box H/ACA
      Ribonucleoproteins) and RNA-independent (protein-only enzymes) mechanisms.

PMID- 21957047
TI  - Techniques for following the movement of single RNAs in living cells.
AB  - The ability to investigate gene expression has evolved from static approaches
      that analyze a population of cells to dynamic approaches that analyze individual
      living cells. During the last decade, a number of different fluorescent methods
      have been developed for monitoring the dynamics of single RNAs in living cells.
      Spatial-temporal analyses of single RNAs in living cells have provided novel
      insight into nuclear transport, RNA localization, and decay. Technical advances
      with these approaches allow for single molecule detection, providing an
      unprecedented view of RNA movement. In this article, we discuss the methods for
      observing single RNAs in living cells, highlighting the advantages and
      limitations of each method.

PMID- 21957049
TI  - The contribution of beta-carotene to vitamin A supply of humans.
AB  - Populations that administer highly restrictive diets using a strong dietary
      regime, excluding certain types of food, might be at risk of vitamin A
      insufficiency, even in developed countries. Thus, provitamin A carotenoids from
      plants represent an additional major dietary source of vitamin A for most of the
      world's population. Our aim was to estimate the contribution of beta-carotene to
      vitamin A supply in industrialized countries using available data from the
      literature. A total of 11 studies from 8 countries were used, representing data
      of 121,256 participants. Intakes of total vitamin A, provitamin A carotenoids,
      including beta-carotene were retrieved and used to calculate the retinol activity
      equivalents (RAE) utilizing current conversion factors. Mean total daily dietary
      intake of RAE was 1083+/-175. The mean beta-carotene intake was 3.9 mg/day.
      Preformed vitamin A accounts for nearly 65% of total vitamin A intake,
      carotenoids make up 35%. No statistical differences between men and women in
      total intake of retinol were observed. We conclude that a safe vitamin A intake
      in general cannot be reached by consuming only one component (vitamin A or beta
      carotene) alone, even in Western countries where animal products are commonly
      available.

PMID- 21957050
TI  - Kojic acid-amino acid amide metal complexes and their melanogenesis inhibitory
      activities.
AB  - Tyrosinase plays a critical role in the early stages of the melanin synthetic
      pathway by catalyzing the oxidation of the substrate. Therefore, tyrosinase
      inhibitors have been intensively studied in both cosmetic and food industries to
      develop hypopigmentary agents and prevent enzymatic browning in food. Previously,
      we reported that kojic acid-amino acid amide (KA-AA-NH(2)) showed enhanced
      tyrosinase inhibitory activity compared with kojic acid alone, but this was not
      observed in a cell test because of poor cell permeability. To enhance cell
      permeability, we prepared copper and zinc complexes of KA-AA-NH(2) and
      characterized them using FT-IR spectroscopy, ESI-MS spectrometry, and inductively
      coupled plasma analysis. We then showed that KA-AA-NH(2) copper complexes
      exhibited melanogenesis inhibitory activity in Mel-Ab cells.

PMID- 21957046
TI  - Mechanisms of endonuclease-mediated mRNA decay.
AB  - Endonuclease cleavage was one of the first identified mechanisms of mRNA decay
      but until recently it was thought to play a minor role to the better-known
      processes of deadenylation, decapping, and exonuclease-catalyzed decay. Most of
      the early examples of endonuclease decay came from studies of a particular mRNA
      whose turnover changed in response to hormone, cytokine, developmental, or
      nutritional stimuli. Only a few of these examples of endonuclease-mediated mRNA
      decay progressed to the point where the enzyme responsible for the initiating
      event was identified and studied in detail. The discovery of microRNAs and RISC
      catalyzed endonuclease cleavage followed by the identification of PIN (pilT N
      terminal) domains that impart endonuclease activity to a number of the proteins
      involved in mRNA decay has led to a resurgence of interest in endonuclease
      mediated mRNA decay. PIN domains show no substrate selectivity and their
      involvement in a number of decay pathways highlights a recurring theme that the
      context in which an endonuclease function is a primary factor in determining
      whether any given mRNA will be targeted for decay by this or the default
      exonuclease-mediated decay processes.

PMID- 21957051
TI  - Noble-metal-based catalysts supported on zeolites and macro-mesoporous metal
      oxide supports for the total oxidation of volatile organic compounds.
AB  - The use of porous materials to eliminate volatile organic compounds (VOCs) has
      proven very effective towards achieving sustainability and environmental
      protection goals. The activity of zeolites and macro-mesoporous metal-oxide
      supports in the total oxidation of VOCs has been investigated, with and without
      noble-metal deposition, to develop highly active catalyst systems where the
      formation of by-products was minimal. The first catalysts employed were zeolites,
      which offered a good activity in the oxidation of VOCs, but were rapidly
      deactivated by coke deposition. The effects of the acido-basicity and ionic
      exchange of these zeolites showed that a higher basicity was related to exchanged
      ions with lower electronegativities, resulting in better catalytic performances
      in the elimination of VOCs. Following on from this work, noble metals were
      deposited onto macro-mesoporous metal-oxide supports to form mono and bimetallic
      catalysts. These were then tested in the oxidation of toluene to study their
      catalytic performance and their deactivation process. PdAu/TiO(2)  and
      PdAu/TiO(2) -ZrO(2) 80/20 catalysts demonstrated the best activity and life span
      in the oxidation of toluene and propene and offered the lowest temperatures for a
      50 % conversion of VOCs and the lowest coke content after catalytic testing.
      Different characterization techniques were employed to explain the changes
      occurring in catalyst structure during the oxidation of toluene and propene.

PMID- 21957052
TI  - Circularly polarized luminescence of rhodamine B in a supramolecular chiral
      medium formed by a vortex flow.
AB  - Sucked into the vortex: Hydrogels with embedded Rhodamine B dye showed stir
      induced circularly polarized luminescence (CPL; see picture), the sense of which
      can be controlled by switching the stir direction from clockwise (CW) to
      counterclockwise (CCW) with slow cooling from the sol to gel states. The chiral
      alignment of the dye was erased by heating the sample above the gel-sol
      transition temperature.

PMID- 21957053
TI  - The stability of immunoglobulin a in human milk and saliva stored on filter paper
      at ambient temperature.
AB  - OBJECTIVES: Immunoglobulin A dominates mucosal surfaces and is a biomarker of
      interest in populations with a high disease burden. The objectives of this work
      are to describe an ELISA for IgA and test the stability of storage on filter
      paper for human milk and saliva collection to be used in remote field locations.
      METHODS: A two-site sandwich ELISA for IgA was developed. To test filter paper
      storage capabilities under field conditions, 248 matched whole and dried human
      milk filter paper samples and 251 matched whole and dried saliva samples were
      collected from northern Kenyan women. Whole samples were frozen in liquid
      nitrogen while dried samples were stored at ambient temperature for up to 8
      weeks. Recovered dried IgA levels were compared to whole IgA levels and adjusted
      for time stored at ambient temperature. RESULTS: The lower limit of
      quantification for this assay is 10.1 ng/ml. Linearity of dilution for human milk
      and saliva samples was excellent. High and low-control coefficient of variation
      values across plates were 9.1 (341.8 ng/ml) and 9.4% (132.5 ng/ml). IgA was
      detected in all whole and dried samples. There is a moderate concordance between
      dried and whole samples (R(2) = 0.62). There is a small but significant effect of
      time stored, with a loss of ~1 MUg/ml per day (P = 0.0052). CONCLUSIONS: This IgA
      assay is a cost-effective alternative to commercial secretory IgA kits. Human
      milk and saliva can be stored on filter paper for up to 8 weeks.

PMID- 21957054
TI  - Structure of transfer RNAs: similarity and variability.
AB  - Transfer RNAs (tRNAs) are ancient molecules whose origin goes back to the
      beginning of life on Earth. Key partners in the ribosome-translation machinery,
      tRNAs read genetic information on messenger RNA and deliver codon specified amino
      acids attached to their distal 3'-extremity for peptide bond synthesis on the
      ribosome. In addition to this universal function, tRNAs participate in a wealth
      of other biological processes and undergo intricate maturation events. Our
      understanding of tRNA biology has been mainly phenomenological, but ongoing
      progress in structural biology is giving a robust physico-chemical basis that
      explains many facets of tRNA functions. Advanced sequence analysis of tRNA genes
      and their RNA transcripts have uncovered rules that underly tRNA 2D folding and
      3D L-shaped architecture, as well as provided clues about their evolution. The
      increasing number of X-ray structures of free, protein- and ribosome-bound tRNA,
      reveal structural details accounting for the identity of the 22 tRNA families
      (one for each proteinogenic amino acid) and for the multifunctionality of a given
      family. Importantly, the structural role of post-transcriptional tRNA
      modifications is being deciphered. On the other hand, the plasticity of tRNA
      structure during function has been illustrated using a variety of technical
      approaches that allow dynamical insights. The large range of structural
      properties not only allows tRNAs to be the key actors of translation, but also
      sustain a diversity of unrelated functions from which only a few have already
      been pinpointed. Many surprises can still be expected.

PMID- 21957056
TI  - Psychometric properties of the Functional Assessment of Chronic Illness Therapy-
      Spiritual Well-being (FACIT-Sp) in an Arabic-speaking, predominantly Muslim
      population.
AB  - OBJECTIVE: This study determined the psychometric properties of the Arabic
      Functional Assessment of Chronic Illness Therapy-Spiritual Well-being (FACIT-Sp)
      Version 4 and explored associations between its three factors (Peace, Meaning,
      and Faith) and health-related quality of life (HrQoL) among Arab patients with
      cancer. METHODS: A total of 205 Arabic-speaking, study-eligible cancer patients
      who were in treatment at the King Hussein Cancer Center, Amman, Jordan, completed
      the FACIT-Sp scale. RESULTS: Cronbach's alpha reliability coefficients suggest
      that the Arabic FACIT-Sp is reliable and that moderate to strong correlations
      among subscales suggest validity. Correlation analyses showed that the 12-item
      Spiritual Well-being scale was associated with Social (r = 0.45, p = 0.01) and
      Functional Well-being (r = 0.48, p = 0.01). Hierarchical multiple regressions
      revealed that the Peace factor added 7.5% and the Meaning factor 3.8% to the
      prediction of HrQoL (p < 0.001). Faith did not significantly contribute to the
      unique prediction of HrQoL. Correlation analyses revealed that Peace was most
      prominently associated with the HrQoL subscale of Functional Well-being (r =
      0.53, p = 0.01). CONCLUSIONS: This first study of Arabic-speaking, predominantly
      Muslim Jordanian cancer patients using the FACIT-Sp indicates that it is a
      psychometrically sound instrument for detailed assessment of the spiritual well
      being of Arabic-speaking cancer patients. The three-factor model appears to allow
      for discrimination among factors that are most highly associated with different
      aspects of HrQoL.

PMID- 21957057
TI  - NMR studies on thermal stability of alpha-helix conformation of melittin in pure
      ethanol and ethanol-water mixture solvents.
AB  - Thermal stability of the alpha-helix conformation of melittin in pure ethanol and
      ethanol-water mixture solvents has been investigated by using NMR spectroscopy.
      With increase in water concentration of the mixture solvents (from 0 wt% to ~71.5
      wt%) as well as temperature (from room temperature to 60  degrees C), the
      intramolecular hydrogen bonds formed in melittin are destabilized and the alpha
      helix is partially uncoiled. Further, the hydrogen bonds are found to be more
      thermally stable in pure ethanol than in pure methanol, suggesting that their
      stability is enhanced with increase in the size of the alkyl groups of alcohol
      molecules.

PMID- 21957058
TI  - Metabolomic analysis reveals differences in urinary excretion of kiwifruit
      derived metabolites in a mouse model of inflammatory bowel disease.
AB  - The interleukin-10-deficient (IL-10(-/-)) mouse, a model of inflammatory bowel
      disease (IBD), develops intestinal inflammation unless raised in germ-free
      conditions. The metabolic effects of consuming extracts from the fruits of yellow
      (Actinidia chinensis) or green-fleshed (A. deliciosa) kiwifruit that displayed in
      vitro anti-inflammatory activity were investigated in IL-10(-/-) mice by
      metabolomic analysis of urine samples. Kiwifruit-derived metabolites were
      detected at significantly higher levels in urine of IL-10(-/-) mice relative to
      those of wild-type mice, indicating that the metabolism of these metabolites was
      affected by IL-10(-/-)-wild-type genotypic differences. Urinary metabolites
      previously associated with inflammation were not altered by the kiwifruit
      extracts. This study demonstrates the use of metabolomic analysis to study
      dietary effects and the influence of genotype on food metabolism, which may have
      implications on the development of functional foods for the treatment of IBD.

PMID- 21957059
TI  - Women have relatively larger brains than men: a comment on the misuse of general
      linear models in the study of sexual dimorphism.
AB  - General linear models (GLM) have become such universal tools of statistical
      inference, that their applicability to a particular data set is rarely
      questioned. These models are designed to minimize residuals along the y-axis,
      while assuming that the predictor (x-axis) is free of statistical noise (ordinary
      least square regression, OLS). However, in practice, this assumption is often
      violated, which can lead to erroneous conclusions, particularly when two
      predictors are correlated with each other. This is best illustrated by two
      examples from the study of allometry, which have received great interest: (1) the
      question of whether men or women have relatively larger brains after accounting
      for body size differences, and (2) whether men indeed have shorter index fingers
      relative to ring fingers (digit ratio) than women. In depth analysis of these
      examples clearly shows that GLMs produce spurious sexual dimorphism in body shape
      where there is none (e.g. relative brain size). Likewise, they may fail to detect
      existing sexual dimorphisms in which the larger sex has the lower trait values
      (e.g. digit ratio) and, conversely, tend to exaggerate sexual dimorphism in which
      the larger sex has the relatively larger trait value (e.g. most sexually selected
      traits). These artifacts can be avoided with reduced major axis regression (RMA),
      which simultaneously minimizes residuals along both the x and the y-axis.
      Alternatively, in cases where isometry can be established there are no objections
      against and good reasons for the continued use of ratios as a simple means of
      correcting for size differences.

PMID- 21957060
TI  - Influence of the chemical structure on the stability and conductance of porphyrin
      single-molecule junctions.

PMID- 21957061
TI  - Riboswitch structure in the ligand-free state.
AB  - Molecular investigations of riboswitches bound to small-molecule effectors have
      produced a wealth of information on how these molecules achieve high affinity and
      specificity for a target ligand. X-ray crystal structures have been determined
      for the ligand-free state for representatives of the preQ1-I, S
      adenosylmethionine I, lysine, and glycine aptamer classes. These structures in
      conjunction with complimentary techniques, such as in-line probing, NMR
      spectroscopy, Forster resonance energy transfer, small-angle scattering, and
      computational simulations, have demonstrated that riboswitches adopt multiple
      conformations in the absence of ligand. Despite a number of investigations that
      support ligand-dependent folding, mounting evidence suggests that free-state
      riboswitches interact with their effectors in the sub-populations of largely
      prefolded states as embodied by the principle of conformational selection, which
      has been documented extensively for protein-mediated ligand interactions.
      Fundamental riboswitch investigations of the bound and free states have advanced
      our understanding of RNA folding, ligand recognition, and how these factors
      culminate in communication between an aptamer and its expression platform. An
      understanding of these topics is essential to comprehend riboswitch gene
      regulation at the molecular level, which has already provided a basis to
      understand the mechanism of action of natural antimicrobials.

PMID- 21957062
TI  - Geometric morphometrics of male facial shape in relation to physical strength and
      perceived attractiveness, dominance, and masculinity.
AB  - OBJECTIVES: Evolutionary psychologists claim that women have adaptive preferences
      for specific male physical traits. Physical strength may be one of those traits,
      because recent research suggests that women rate faces of physically strong men
      as more masculine, dominant, and attractive. Yet, previous research has been
      limited in its ability to statistically map specific male facial shapes and
      features to corresponding physical measures (e.g., strength) and ratings (e.g.,
      attractiveness). METHODS: The association of handgrip strength (together with
      measures of shoulder width, body height, and body fat) and women's ratings of
      male faces (concerning dominance, masculinity, and attractiveness) were studied
      in a sample of 26 Caucasian men (aged 18-32 years). Geometric morphometrics was
      used to statistically assess the covariation of male facial shape with these
      measures. Statistical results were visualized with thin-plate spline deformation
      grids along with image unwarping and image averaging. RESULTS: Handgrip strength
      together with shoulder width, body fat, dominance, and masculinity loaded
      positively on the first dimension of covariation with facial shape (explaining
      72.6%, P < 0.05). These measures were related to rounder faces with wider
      eyebrows and a prominent jaw outline while highly attractive and taller men had
      longer, narrower jaws and wider/fuller lips. CONCLUSIONS: Male physical strength
      was more strongly associated with changes in face shape that relate to perceived
      masculinity and dominance than to attractiveness. Our study adds to the growing
      evidence that attractiveness and dominance/masculinity may reflect different
      aspects of male mate quality.

PMID- 21957063
TI  - Genetic variations involved in interindividual variability in carotenoid status.
AB  - As shown in most clinical studies dedicated to carotenoids, there is a huge
      interindividual variability in absorption, and blood and tissue responses, of
      dietary carotenoids. The recent discovery that several proteins are involved in
      carotenoid metabolism in humans has prompted a possible explanation for this
      phenomenon: genetic variants in genes encoding for these proteins may affect
      their expression or activity, and in turn carotenoid metabolism and carotenoid
      status. The proteins clearly identified so far are (i) the carotene oxygenases
      beta,beta-carotene-15,15'-monooxygenase (BCMO1) and beta,beta-carotene-9',10'
      oxygenase (BCDO2), which are involved in carotenoid cleavage, (ii) scavenger
      receptor class B type I (SR-BI), cluster determinant 36 (CD36), and Niemann Pick
      C1-like 1 (NPC1L1), which are involved in carotenoid uptake by cells, and (iii)
      glutathione S-transferase Pi 1 (GSTP1) and human retinal lutein-binding protein
      (HR-LBP), which are involved in the transport of xanthophylls in the retina.
      Other proteins, such as ATP-binding cassette subfamily G member 5 (ABCG5) and the
      fatty acid-binding proteins (FABPs) are also apparently involved although firmer
      evidence is still required. A genome-wide association study, as well as several
      candidate gene association studies, has shown that groups of subjects bearing
      different alleles in single nucleotide polymorphisms located in or near several
      of the above-mentioned genes display different blood and/or tissue concentrations
      of carotenoids. Further studies are needed to identify all the proteins involved
      in carotenoid metabolism and assess whether other types of genetic variation,
      e.g. copy number variants and epigenetic modifications, can modulate carotenoid
      status. One potential application of such research could be personalized dietary
      guidelines for carotenoids according to individual genetic characteristics.

PMID- 21957064
TI  - Ontogenetic allometry and cranial shape diversification among human populations
      from South America.
AB  - Modifications of ontogenetic allometries play an important role in patterning the
      shape differentiation among populations. This study evaluates the influence of
      size variation on craniofacial shape disparity among human populations from South
      America and assesses whether the morphological disparity observed at the
      interpopulation level resulted from a variable extension of the same ontogenetic
      allometry, or whether it arose as a result of divergences in the pattern of size
      related shape changes. The size and shape of 282 adult and subadult crania were
      described by geometric morphometric-based techniques. Multivariate regressions
      were used to evaluate the influence of size on shape differentiation between and
      within populations, and phylogenetic comparative methods were used to take into
      account the shared evolutionary history among populations. The phylogenetic
      generalized least-squares models showed that size accounts for a significant
      amount of shape variation among populations for the vault and face but not for
      the base, suggesting that the three modules did not exhibit a uniform response to
      changes in overall growth. The common slope test indicated that patterns of
      evolutionary and ontogenetic allometry for the vault and face were similar and
      characterized by a heightening of the face and a lengthening of the vault with
      increasing size. The conservation of the same pattern of shape changes with size
      suggests that differences in the extent of growth contributed to the
      interpopulation cranial shape variation and that certain directions of
      morphological change were favored by the trait covariation along ontogeny.

PMID- 21957066
TI  - Chemical synthesis of the S-linked glycopeptide, sublancin.
AB  - Sublancin is an S-linked glycopeptide produced by Bacillus subtilis 168 and
      consists of 37 amino acid residues with two disulfide bonds. In this study, we
      synthesized sublancin by Fmoc-based solid-phase peptide synthesis and
      chemoselective disulfide formation reactions.

PMID- 21957068
TI  - Retraction. Effects of open-air temperature on air temperature inside biological
      safety cabinet.

PMID- 21957069
TI  - One hundred years of the Fritz Haber Institute.
AB  - We outline the institutional history and highlight aspects of the scientific
      history of the Fritz Haber Institute (FHI) of the Max Planck Society, successor
      to the Kaiser Wilhelm Institute for Physical Chemistry and Electrochemistry, from
      its founding in 1911 until about the turn of the 21st century. Established as one
      of the first two Kaiser Wilhelm Institutes, the Institute began as a much-awaited
      remedy for what prominent German chemists warned was the waning of Germany's
      scientific and technological superiority relative to the United States and to
      other European nations. The history of the Institute has largely paralleled that
      of 20th century Germany. It spearheaded the research and development of chemical
      weapons during World War I, then experienced a "golden era" during the 1920s and
      early 1930s, in spite of financial hardships. Under the National Socialists it
      suffered a purge of its scientific staff and a diversion of its research into the
      service of the new regime, accompanied by a breakdown in its international
      relations. In the immediate aftermath of World War II it suffered crippling
      material losses, from which it recovered slowly in the postwar era. In 1952, the
      Institute took the name of its founding director and the following year joined
      the fledgling Max Planck Society, successor to the Kaiser Wilhelm Society. During
      the 1950s and 1960s, the Institute supported diverse research into the structure
      of matter and electron microscopy in its geographically isolated and politically
      precarious location in West Berlin. In subsequent decades, as Berlin benefited
      from the policies of detente and later glasnost and the Max Planck Society
      continued to reassess its preferred model of a research institute, the FHI
      reorganized around a board of coequal scientific directors and renewed its focus
      on the investigation of elementary processes on surfaces and interfaces, topics
      of research that had been central to the work of Fritz Haber and the first
      "golden era" of the Institute. Throughout its one-hundred-year history, the
      Institute's pace-setting research has been shaped by dozens of distinguished
      scientists, among them seven Nobel laureates. Here we highlight the contributions
      made at the Institute to the fields of gas-phase kinetics and dynamics, early
      quantum physics, colloid chemistry, electron microscopy, and surface chemistry,
      and we give an account of the key role the Institute played in implementing the
      Berlin Electron Synchrotron (BESSY I and II). Current research at the Institute
      in surface science and catalysis as well as molecular physics and spectroscopy is
      exemplified in this issue [Angew. Chem. 2011, 123, 10242; Angew. Chem. Int. Ed.
      2011, 50, 10064].

PMID- 21957070
TI  - Human neoteny revisited: The case of synaptic plasticity.
AB  - The process of learning requires morphological changes in the neuronal
      connections and the formation of new synapses. Due to the importance of memory
      and learning in our species, it has been suggested that the synaptic plasticity
      in a number of association areas is higher in the human brain than in other
      primates. Cortical neurons in mammals are characterized by higher metabolism,
      activity, and synaptic plasticity during development and the juvenile stage than
      in the adult. In Homo sapiens, brain development is retarded compared with other
      primates, especially in some association areas. These areas are characterized by
      the presence of neurons, which remain structurally immature throughout their
      lifespans and show an increase in the expression of the genes, which deal with
      metabolism and the activity and synaptic plasticity in adulthood. The retention
      of juvenile features in some adult neurons in our species has occurred in areas,
      which are related to episodic memory, planning, and social navigation. The
      increase of the aerobic metabolism in these neurons may lead, however, to higher
      levels of oxidative stress, therefore, favoring the development of
      neurodegenerative diseases which are exclusive, or almost exclusive, to humans,
      such as Alzheimer's disease.

PMID- 21957072
TI  - A single-molecule view of chaperonin cooperativity.

PMID- 21957071
TI  - Antiapoptotic protein Lifeguard is required for survival and maintenance of
      Purkinje and granular cells.
AB  - Lifeguard (LFG) is an inhibitor of Fas-mediated cell death and is highly
      expressed in the cerebellum. We investigated the biological role of LFG in the
      cerebellum in vivo, using mice with reduced LFG expression generated by shRNA
      lentiviral transgenesis (shLFG mice) as well as LFG null mice. We found that LFG
      plays a role in cerebellar development by affecting cerebellar size, internal
      granular layer (IGL) thickness, and Purkinje cell (PC) development. All these
      features are more severe in early developmental stages and show substantial
      recovery overtime, providing a remarkable example of cerebellar plasticity. In
      adult mice, LFG plays a role in PC maintenance shown by reduced cellular density
      and abnormal morphology with increased active caspase 8 and caspase 3
      immunostaining in shLFG and knockout (KO) PCs. We studied the mechanism of action
      of LFG as an inhibitor of the Fas pathway and provided evidence of the
      neuroprotective role of LFG in cerebellar granule neurons (CGNs) and PCs in an
      organotypic cerebellar culture system. Biochemical analysis of the Fas pathway
      revealed that LFG inhibits Fas-mediated cell death by interfering with caspase 8
      activation. This result is supported by the increased number of active caspase 8
      positive PCs in adult mice lacking LFG. These data demonstrate that LFG is
      required for proper development and survival of granular and Purkinje cells and
      suggest LFG may play a role in cerebellar disorders.

PMID- 21957073
TI  - Unraveling the hydrophobic effect, one molecule at a time.

PMID- 21957076
TI  - Bilberries and their anthocyanins ameliorate experimental colitis.
AB  - Bilberries have positive effects in acute and chronic diarrhea. Patients with
      inflammatory bowel disease (IBD) report on improved symptoms upon ingestion.
      Bilberries contain approximately 10% of anthocyanins (ACs), which have anti
      oxidative, anti-carcinogenic, and anti-inflammatory properties. We investigated
      whether experimental colitis can be ameliorated by dried bilberries or ACs. Acute
      and chronic dextrane sodium sulphate (DSS) colitis were induced in Balb/c mice by
      2.5% DSS in the drinking water. Mice were fed with dried bilberries or ACs,
      respectively. Cytokines were determined in supernatants from mesenteric lymph
      nodes (MLNs) by ELISA and apoptosis was investigated by terminal deoxynucleotidyl
      transferase biotin-dUTP nick end labeling assays. Oral administration of
      bilberries during acute DSS-induced colitis ameliorated disease severity and
      reduced secretion of IFN-gamma and tumor necrosis factor from mesenteric lymph
      node cells. Dried bilberries also improved chronic DSS-colitis. Ingestion of ACs
      reduced intestinal inflammation in acute and chronic DSS-colitis with decreased
      histological scores and cytokine secretion. Both bilberries and ACs prevented
      inflammation-induced apoptosis in colonic epithelial cells. Taken together,
      ingestion of dried bilberries had positive effects on various parameters
      especially in acute DSS-colitis. Oral administration of ACs resulted in an
      amelioration of acute colitis as well as chronic colitis. These promising results
      justify a clinical study on their therapeutic effect in inflammatory bowel
      disease patients.

PMID- 21957077
TI  - Vesicular glutamate transporter immunoreactivity in the periodontal ligament of
      the rat incisor.
AB  - The distribution of three vesicular glutamate transporter (VGluT) isoforms,
      VGluT1, VGluT2, and VGluT3, were investigated in the trigeminal ganglion of the
      periodontal ligament in the rat incisor-a receptive field of trigeminal ganglion
      neurons. In the trigeminal ganglion, mRNAs for all VGluT isoforms were detected
      and proteins were observed in the cytoplasm of trigeminal ganglion cells. VGluT1
      immunoreactions were localized within the cytoplasm for all sizes of trigeminal
      neurons, although predominately in medium-large trigeminal neurons. Double
      labeling showed that most VGluT1 contained both VGluT2 and VGluT3. In the
      periodontal ligament of the incisor, the Ruffini endings, principal periodontal
      mechanoreceptors, displayed VGluT1 and VGluT2 immunoreactivities. However, lacked
      immunoreactions for VGluT3. At the electron microscopic level, VGluT1
      immunoreactions were localized around the vesicle membranes at the axon terminal
      of Ruffini endings. The present results indicate that VGluT is expressed in the
      sensory nerve endings where apparent synapses are not present. Thus, glutamate in
      the sensory nerve endings is thought to be used in metabotropic functions. This
      is because glutamate is a general metabolic substrate, and/or acts as a
      neurotransmitter as proposed in muscle spindles.

PMID- 21957083
TI  - Lipopolysaccharide-induced in vivo activation of follicular dendritic cells is
      tumor necrosis factor receptor-1 independent.
AB  - It is well recognized that tumor necrosis factor receptor-1 (TNFR1) signaling
      pathway (with lymphotoxin-beta receptor) is of critical importance for the
      development, activation, and clustering of follicular dendritic cells (FDCs)
      within the lymphoid follicles. However, further information on the molecular
      control of these processes is very sparse. Here, we show that intravenous
      application of lipopolysaccharide induces the clear and prominent morphological
      signs of FDC development and activation in vivo, which is independent of TNFR1
      pathway.

PMID- 21957084
TI  - Heteromeric assembled polypeptidic artificial hydrolases with a six-helical
      bundle scaffold.
AB  - Enzyme efficiency results from the cooperation of functional groups in the
      catalytic site. In order to mimic a natural enzyme, a definite 3D scaffold must
      be carefully designed so that the functional groups can work cooperatively.
      During the HIV-1 fusion process, the gp41 N- and C-terminal heptad repeat regions
      form a coiled-coil six-helical bundle (6HB) that brings the viral and target cell
      membranes into close proximity for fusion. We used 6HB as the molecular model for
      a novel scaffold for the design of an artificial enzyme, in which the modified
      C34 and N36 peptides formed a unique 6HB structure through specific molecular
      recognition, and the position and orientation of the side-chain groups on this
      scaffold were predictable. The histidine modified 6HB C34(H13/20)/N36(H15/22)
      showed enzyme-like hydrolytic activity towards p-nitrophenyl acetate (PNPA;
      k(cat)/K(M) =3.66 M(-1) s(-1)) through the cooperation of several inter- or
      intrahelical imidazole groups. Since the catalytic activity of 6HB depends on the
      C- and N-peptide assembly, either HIV fusion inhibitors that can compete with the
      formation of catalytic 6HB or denaturants that can destroy the ordered structure
      were able to modulate its activity. Further engineering of the solvent-exposing
      face with Glu(-)-Lys(+) salt bridges enhanced the helicity and the stability of
      6HB. As a result, the population and stability of cooperative catalytic units
      increased. In addition, the Glu(-)-Lys(+) -stabilized 6HB
      SC35(H13/20)/N36(H15/22) had increased catalytic efficiency (k(cat)/K(M) =6.30 M(
      1) s(-1)). A unique 6HB system was specifically assembled and provided a scaffold
      sufficiently stable to mimic the function of enzymes or other biomolecules.

PMID- 21957085
TI  - The diffusion of innovation in nursing regulatory policy: removing a barrier to
      medication administration training for child care providers.
AB  - Safe medication administration is an essential component of high-quality child
      care. Its achievement in New Jersey was impeded by a controversy over whether
      teaching child care providers medication administration involves registered
      nurses in the process of nursing delegation. Through the theoretical framework of
      the Diffusion of Innovation, this paper examines how the interpretation of
      regulatory policy related to nursing practice in New Jersey was adjusted by the
      Board of Nursing following a similar interpretation of regulatory policy by the
      Board of Nursing in Connecticut. This adjustment enabled New Jersey nurses to
      continue medication administration training for child care providers. National
      data supporting the need for training child care providers in medication
      administration is presented, the Diffusion of Innovation paradigm is described;
      the Connecticut case and the New Jersey dilemma are discussed; the diffusion
      process between the two states is analyzed and an assessment of the need for
      further change is made.

PMID- 21957086
TI  - Late pulmonary metastases of a giant-cell tumour of the spine.

PMID- 21957087
TI  - Sometimes happy people focus on the trees and sad people focus on the forest:
      context-dependent effects of mood in impression formation.
AB  - Research indicates that affect influences whether people focus on categorical or
      behavioral information during impression formation. One explanation is that
      affect confers its value on whatever cognitive inclinations are most accessible
      in a given situation. Three studies tested this malleable mood effects
      hypothesis, predicting that happy moods should maintain and unhappy moods should
      inhibit situationally dominant thinking styles. Participants completed an
      impression formation task that included categorical and behavioral information.
      Consistent with the proposed hypothesis, no fixed relation between mood and
      processing emerged. Whether happy moods led to judgments reflecting category
      level or behavior-level information depended on whether participants were led to
      focus on the their immediate psychological state (i.e., current affective
      experience; Studies 1 and 2) or physical environment (i.e., an unexpected odor;
      Study 3). Consistent with research on socially situated cognition, these results
      demonstrate that the same affective state can trigger entirely different thinking
      styles depending on the context.

PMID- 21957088
TI  - Frogs and ponds: a multilevel analysis of the regulatory mode complementarity
      hypothesis.
AB  - Regulatory mode is a psychological construct pertaining to the self-regulatory
      orientation of individuals or teams engaged in goal pursuit. Locomotion, the
      desire for continuous progress or movement in goal pursuit, and assessment, the
      desire to critically evaluate and compare goals and means, are orthogonal
      regulatory modes. However, they are also complementary, in that both locomotion
      and assessment are necessary for effectual goal pursuit. In the present research,
      the authors sought to demonstrate that multilevel regulatory mode complementarity
      can positively affect individual-level performance on goal-relevant tasks. The
      authors recruited 289 employees (177 men, 112 women) from preexisting work teams
      in workplace organizations in Italy and obtained (a) employees' individual-level
      scores on the Regulatory Mode Scale and (b) supervisor ratings of each employee's
      work performance. The results supported the multilevel complementarity hypothesis
      for regulatory mode. Limitations and recommendations for future research are
      discussed.

PMID- 21957089
TI  - Baicalein inhibits oxidative stress-induced cellular damage via antioxidant
      effects.
AB  - Baicalein (5,6,7-trihydroxyflavone) is a phenolic flavonoid compound derived
      mainly from the root of Scutellaria baicalensis Georgi, a medicinal plant
      traditionally used in oriental medicine. In our previous study, baicalein
      attenuated mitochondrial oxidative stress by scavenging reactive oxygen species
      (ROS) and by induction of nuclear factor erythroid 2-related factor 2
      transcription factor-mediated manganese superoxide dismutase. In the present
      study, the protective effects of baicalein against oxidative stress-induced
      damage, especially cellular components including DNA, lipid, and protein, were
      studied. The results of this study showed that baicalein scavenged intracellular
      ROS. Baicalein inhibited the H2O2-induced DNA damage that was demonstrated by
      decreased phospho-H2A.X expression and DNA tail formation. In addition, it
      prevented the lipid peroxidation shown by the fluorescence intensity of diphenyl
      1-pyrenylphosphine and the formation of thiobarbituric acid reactive substances.
      Moreover, baicalein inhibited protein oxidation demonstrated by protein carbonyl
      formation. Furthermore, baicalein protected cells via the inhibition of apoptosis
      induced by H2O2. The findings of this study suggest that baicalein provides
      protection for cellular components against oxidative damage via scavenging ROS
      and inhibiting apoptosis.

PMID- 21957090
TI  - Dispersal of Symbiodinium by the stoplight parrotfish Sparisoma viride.
AB  - Environmental reservoirs of zooxanthellae are essential for coral larvae
      settlement; understanding where they occur and how they are maintained is
      important for coral reef ecology. This study investigated the dispersal of
      Symbiodinium spp. by the stoplight parrotfish Sparisoma viride, which had high
      mean densities of viable and cultivable Symbiodinium (3207-8900 cells ml(-1)) in
      faeces. Clades A, B and G were detected using amplified chloroplast ribosomal
      sequences (cp23S-HVR), and corresponded with diet preferences of fish and the
      environmental Symbiodinium diversity of the region. Cells are constantly
      dispersed in the water column and deposited in the substrate at a local level (86
      +/- 17.8 m(2)), demonstrating that parrotfishes are vectors for short-distance
      dispersal of zooxanthellae. Such dispersal could constitute a key role in the
      maintenance of environmental Symbiodinium reservoirs.

PMID- 21957091
TI  - How global extinctions impact regional biodiversity in mammals.
AB  - Phylogenetic diversity (PD) represents the evolutionary history of a species
      assemblage and is a valuable measure of biodiversity because it captures not only
      species richness but potentially also genetic and functional diversity.
      Preserving PD could be critical for maintaining the functional integrity of the
      world's ecosystems, and species extinction will have a large impact on ecosystems
      in areas where the ecosystem cost per species extinction is high. Here, we show
      that impacts from global extinctions are linked to spatial location. Using a
      phylogeny of all mammals, we compare regional losses of PD against a model of
      random extinction. At regional scales, losses differ dramatically: several
      biodiversity hotspots in southern Asia and Amazonia will lose an unexpectedly
      large proportion of PD. Global analyses may therefore underestimate the impacts
      of extinction on ecosystem processes and function because they occur at finer
      spatial scales within the context of natural biogeography.

PMID- 21957092
TI  - Brain development and predation: plastic responses depend on evolutionary
      history.
AB  - Although the brain is known to be a very plastic organ, the effects of common
      ecological interactions like predation or competition on brain development have
      remained largely unexplored. We reared nine-spined sticklebacks (Pungitius
      pungitius) from two coastal marine (predation-adapted) and two isolated pond
      (competition-adapted) populations in a factorial experiment, manipulating
      perceived predatory risk and food supply to see (i) if the treatments affected
      brain development and (ii) if there was population differentiation in the
      response to treatments. We detected differences in plasticity of the bulbus
      olfactorius (chemosensory centre) between habitats: marine fish were not plastic,
      whereas pond fish had larger bulbi olfactorii in the presence of perceived
      predation. Marine fish had larger bulbus olfactorius overall. Irrespective of
      population origin, the hypothalamus was smaller in the presence of perceived
      predatory risk. Our results demonstrate that perceived predation risk can
      influence brain development, and that the effect of an environmental factor on
      brain development may depend on the evolutionary history of a given population in
      respect to this environmental factor.

PMID- 21957094
TI  - Aclidinium inhibits human lung fibroblast to myofibroblast transition.
AB  - BACKGROUND: Fibroblast to myofibroblast transition is believed to contribute to
      airway remodelling in lung diseases such as asthma and chronic obstructive
      pulmonary disease. This study examines the role of aclidinium, a new long-acting
      muscarinic antagonist, on human fibroblast to myofibroblast transition. METHODS:
      Human bronchial fibroblasts were stimulated with carbachol (10(-8) to 10(-5) M)
      or transforming growth factor-beta1 (TGF-beta1; 2 ng/ml) in the presence or
      absence of aclidinium (10(-9) to 10(-7) M) or different drug modulators for 48 h.
      Characterisation of myofibroblasts was performed by analysis of collagen type I
      and alpha-smooth muscle actin (alpha-SMA) mRNA and protein expression as well as
      alpha-SMA microfilament immunofluorescence. ERK1/2 phosphorylation, RhoA-GTP and
      muscarinic receptors (M) 1, 2 and 3 protein expression were determined by western
      blot analysis and adenosine 3'-5' cyclic monophosphate levels were determined by
      ELISA. Proliferation and migration of fibroblasts were also assessed. RESULTS:
      Collagen type I and alpha-SMA mRNA and protein expression, as well as percentage
      alpha-SMA microfilament-positive cells, were upregulated in a similar way by
      carbachol and TGF-beta1, and aclidinium reversed these effects. Carbachol-induced
      myofibroblast transition was mediated by an increase in ERK1/2 phosphorylation,
      RhoA-GTP activation and cyclic monophosphate downregulation as well as by the
      autocrine TGF-beta1 release, which were effectively reduced by aclidinium. TGF
      beta1 activated the non-neuronal cholinergic system. Suppression of M1, M2 or M3
      partially prevented carbachol- and TGF-beta1-induced myofibroblast transition.
      Aclidinium dose-dependently reduced fibroblast proliferation and migration.
      CONCLUSION: Aclidinium inhibits human lung fibroblast to myofibrobast transition.

PMID- 21957096
TI  - In pursuit of Irving and Scholander: a review of oxygen store management in seals
      and penguins.
AB  - Since the introduction of the aerobic dive limit (ADL) 30 years ago, the concept
      that most dives of marine mammals and sea birds are aerobic in nature has
      dominated the interpretation of their diving behavior and foraging ecology.
      Although there have been many measurements of body oxygen stores, there have been
      few investigations of the actual depletion of those stores during dives. Yet, it
      is the pattern, rate and magnitude of depletion of O(2) stores that underlie the
      ADL. Therefore, in order to assess strategies of O(2) store management, we review
      (a) the magnitude of O(2) stores, (b) past studies of O(2) store depletion and
      (c) our recent investigations of O(2) store utilization during sleep apnea and
      dives of elephant seals (Mirounga angustirostris) and during dives of emperor
      penguins (Aptenodytes forsteri). We conclude with the implications of these
      findings for (a) the physiological responses underlying O(2) store utilization,
      (b) the physiological basis of the ADL and (c) the value of extreme hypoxemic
      tolerance and the significance of the avoidance of re-perfusion injury in these
      animals.

PMID- 21957095
TI  - The long way down--are carbon and oxygen isotope signals in the tree ring
      uncoupled from canopy physiological processes?
AB  - The carbon (delta(13)C) and oxygen (delta(18)O) stable isotope composition is
      widely used to obtain information on the linkages between environmental drivers
      and tree physiology over various time scales. The tree-ring archive can
      especially be exploited to reconstruct inter- and intra-annual variation of both
      climate and physiology. There is, however, a lack of information on the processes
      potentially affecting delta(13)C and delta(18)O on their way from assimilation in
      the leaf to the tree ring. As a consequence, the aim of this study was to trace
      the isotope signals in European beech (Fagus sylvatica L.) from leaf water
      (delta(18)O) and leaf assimilates (delta(13)C and delta(18)O) to tree-ring wood
      via phloem-transported compounds over a whole growing season. Phloem and leaf
      samples for delta(13)C and delta(18)O analyses as well as soil water, xylem
      water, leaf water and atmospheric water vapour samples for delta(18)O analysis
      were taken approximately every 2 weeks during the growing season of 2007. The
      delta(13)C and delta(18)O samples from the tree rings were dated intra-annually
      by monitoring the tree growth with dendrometers. delta(18)O in the phloem organic
      matter and tree-ring whole wood was not positively related to leaf water
      evaporative enrichment and delta(18)O of canopy organic matter pools. This
      finding implies a partial uncoupling of the tree-ring oxygen isotopic signal from
      canopy physiology. At the same time, internal carbon storage and remobilization
      physiology most likely prevented delta(13)C in tree-ring whole wood from being
      closely related to intra-annual variation in environmental drivers. Taking into
      account the post-photosynthetic isotope fractionation processes resulting in
      alterations of delta(13)C and delta(18)O not only in the tree ring but also in
      phloem carbohydrates, as well as the intra-annual timing of changes in the tree
      internal physiology, might help to better understand the meaning of the tree-ring
      isotope signal not only intra- but also inter-annually.

PMID- 21957097
TI  - Skin impulse excitation of spinal sensory neurons in developing Xenopus laevis
      (Daudin) tadpoles.
AB  - Responses to gentle touch in young Xenopus tadpoles are mediated by spinal cord
      sensory Rohon-Beard neurons. Tadpoles also respond to noxious stimuli that elicit
      'skin impulses', which propagate between epithelial cells over the whole body
      surface, somehow entering the CNS to generate a response. After hatching (~48 h
      post-fertilization), skin impulse signals enter the CNS only via cranial nerves,
      but previous evidence suggested the possibility of direct entry to the spinal
      cord before this (~24 h). We have used behavioural and electrophysiological
      methods to explore the developmental pattern of skin impulse entry into the
      spinal cord and the involvement of Rohon-Beard neurons. Lesioning confirmed that
      skin impulse signals can directly enter the spinal cord in young embryos, but
      access decreases over ~12 h and disappears soon after hatching. Electrical
      recordings from central Rohon-Beard axons in young embryos showed firing in
      response to skin impulses. However, unit recordings from Rohon-Beard somata
      showed that individuals that responded to touch within a characteristic,
      localised receptive field did not fire to skin impulses, whereas others from
      similar locations responded reliably. Developmental loss of skin impulse access
      to the spinal cord mirrored the known spread of sensitivity to gentle touch as
      the peripheral mechanosensory endings of Rohon-Beard neurons mature. Together,
      these results suggest that Rohon-Beard neurons respond to skin impulses only
      while immature, providing a transitory route for skin impulses to excite the CNS.
      In this way, Rohon-Beard neurons would mediate responses first to noxious and
      then to localised, gentle touch stimuli as the neurons developed.

PMID- 21957098
TI  - Extracoelenteric zooplankton feeding is a key mechanism of nutrient acquisition
      for the scleractinian coral Galaxea fascicularis.
AB  - Internal and external feeding on zooplankton may provide scleractinian corals
      with important nutrients. However, the latter process has never been properly
      quantified. To quantify the dynamics of zooplankton capture, digestion and
      release for a scleractinian coral, we performed detailed video analyses of
      Galaxea fascicularis feeding on Artemia nauplii. A highly dynamic process of prey
      capture, digestion and release was observed. A single G. fascicularis polyp (N=3)
      captured 558+/-67 and released 383+/-75 Artemia nauplii over a 6 h interval. On
      average, 98.6% of prey captured was not ingested. Instead, prey items were
      clustered into aggregates that were digested externally by mesenterial filaments.
      In addition, we employed carbon, nitrogen and phosphorus analysis of zooplankton
      before and after digestion by G. fascicularis colonies (N=6). For total organic
      carbon, 43.1% (0.298+/-0.148 MUg Artemia(-1)) was lost after 6 h of digestion.
      For total organic nitrogen, total organic phosphorus and orthophosphate (PO(4)(3
      )), these values were 51.3% (0.059+/-0.028 MUg Artemia(-1)), 50.9% (0.009+/-0.004
      MUg Artemia(-1)) and 84.6% (0.0019+/-0.0008 MUg Artemia(-1)), respectively. For
      extracoelenteric zooplankton feeding alone, total estimated nutrient inputs for
      G. fascicularis colonies were 76.5+/-0.0 MUg organic carbon, 15.2+/-0.0 MUg
      organic nitrogen, 2.3+/-0.2 MUg organic phosphorus and 0.5+/-0.8 MUg inorganic
      phosphorus per cm(2) coral tissue per day. These values exceed calculations based
      on intracoelenteric feeding by up to two orders of magnitude. Our results
      demonstrate that extracoelenteric zooplankton feeding is a key mechanism of
      nutrient acquisition for a scleractinian coral. These results are of importance
      to coral aquaculture and our understanding of benthic-pelagic coupling on coral
      reefs.

PMID- 21957099
TI  - Role of the lateral line mechanosensory system in directionality of goldfish
      auditory evoked escape response.
AB  - Goldfish (Carassius auratus) escape responses to sudden auditory stimuli are
      mediated by a pair of reticulospinal neurons, the Mauthner (M-) cells, which
      integrate mechanosensory inputs from the inner ear and the lateral line (LL) to
      initiate a fast directional response away from the aversive stimulus. This
      behavior is context dependent; when near an obstruction the fish may rather turn
      towards the sound to avoid hitting the object. Mechanisms underlying this
      directionality remain unknown. Here we investigate the contribution of the LL
      system to auditory evoked escapes and provide behavioral evidence that it
      transmits stimulus - and environmental-dependent information that determines the
      initial response direction of the escape. We quantified escape latency,
      probability and directionality following abrupt sound stimuli before and after
      removal of the entire LL with 0.03 mmol l(-1) cobalt chloride (CoCl(2)), 0.002%
      gentamicin or selective posterior LL nerve (pLLn) transection. CoCl(2)
      significantly increased escape onset latency without affecting probability and
      reduced open field directionality from 77% to chance, 52%. This effect on
      directionality was also observed with gentamicin. Transection of the pLLn had no
      effect on directionality, indicating the anterior LL nerve (aLLn) afferents are
      more likely to transmit directional information to the M-cell. When the fish were
      near a wall, the error rate was quadrupled by both CoCl(2) and pLLn transection.
      Visual elimination had no influence on directionality unless combined with LL
      elimination.

PMID- 21957100
TI  - Characteristics of the anterior lateral line nerve input to the Mauthner cell.
AB  - The goldfish Mauthner (M-) cells, a bilateral pair of reticulospinal neurons,
      initiate the auditory evoked escape behavior of teleosts. In an open field the
      fish reliably turns away from the sound source. This implies that the M-cells are
      capable of a decision-making process that requires the two cells to receive
      differential directional inputs. Recent studies have indicated that the lateral
      line (LL) system is necessary in the initial directionality of the escape. This
      information is thought to be transmitted to the M-cell by the anterior branch of
      the lateral line nerve (aLLn), which has a shorter conduction time then the
      posterior branch. This study is the first attempt to characterize the inputs from
      the aLLn to the M-cell. M-cell intracellular responses to aLLn stimulation
      indicate a fast monosynaptic input (0.80+/-0.03 ms) that has a small amplitude
      averaging 5.85+/-0.42 mV. This input is bilateral and has a significantly longer
      latency and smaller amplitude in the contralateral M-cell. Superimposed on the
      evoked excitatory postsynaptic potential (EPSP) is a shunting inhibition with a
      delay of 1 ms, which is characteristic of other sensory inputs to the M-cell.
      Pharmacological manipulation and 50 Hz stimulation reveal a component of the
      evoked EPSP that is electrotonic, a property favoring speed of transmission. In
      addition, this input is localized to the lateral dendrite proximal to the inputs
      from the inner ear. The short latency of these inputs and their proximity to the
      posterior eighth nerve afferents indicate a crucial role for the aLLn in
      influencing the excitability and directionality of the M-cell.

PMID- 21957101
TI  - The development of endotoxin tolerance, and the role of hypothalamo-pituitary
      adrenal function and glucocorticoids in Pekin ducks.
AB  - Endotoxin tolerance represents a state of abated immunological responsiveness to
      pyrogens, which, in mammals, leads to the decline or abolition of the fever
      response. The development of endotoxin tolerance in birds is not well understood;
      consequently, the impact of repeated pathogenic exposure on the avian febrile
      response, and thus on the ability of birds to fight recurrent infection, is not
      known. We determined the effect of repeated injections of lipopolysaccharide
      (LPS) on the febrile response of Pekin ducks. We gave ducks five injections of
      LPS, spaced 1, 4 or 10 days apart, and recorded their core body temperature with
      abdominally implanted temperature data loggers. Once we established that Pekin
      ducks developed endotoxin tolerance, we investigated the effect of repeated
      injections of LPS on the central and peripheral segments of the hypothalamo
      pituitary-adrenal (HPA) axis in an attempt to elucidate the role of
      glucocorticoids in the modulation of the febrile response during the tolerant
      period. When our ducks became tolerant to LPS, they had significantly higher
      basal levels of plasma corticosterone (CORT, the principal glucocorticoid in
      birds), and their HPA response to treatment with LPS was blunted. We propose that
      the augmented levels of basal plasma CORT resulted from sensitized HPA function,
      and this, in turn, contributed to the development of endotoxin tolerance.
      Regulation of the circulating level of CORT might be a possible target for the re
      establishment of appropriate immune responses in birds.

PMID- 21957102
TI  - Differential segmental strain during active lengthening in a large biarticular
      thigh muscle during running.
AB  - The iliotibialis lateralis pars postacetabularis (ILPO) is the largest muscle in
      the hindlimb of the guinea fowl and is thought to play an important role during
      the stance phase of running, both absorbing and producing work. Using
      sonomicrometry and electromyography, we examined whether the ILPO experiences
      differential strain between proximal, central and distal portions of the
      posterior fascicles. When the ILPO is being lengthened while active, the distal
      portion was found to lengthen significantly more than either the proximal or
      central portions of the muscle. Our data support the hypothesis that the distal
      segment lengthened farther and faster because it began activity at shorter
      sarcomere lengths on the ascending limb of the length-tension curve. Probably
      because of the self-stabilizing effects of operating on the ascending limb of the
      length-tension curve, all segments reached the end of lengthening and started
      shortening at the same sarcomere length. During shortening, this similarity in
      sarcomere length among the segments was maintained, as predicted from force
      velocity effects, and shortening strain was similar in all segments. The
      differential active strain during active lengthening is thus ultimately
      determined by differences in strain during the passive portion of the cycle. The
      sarcomere lengths of all segments of the fascicles were similar at the end of
      active shortening, but after the passive portion of the cycle the distal segment
      was shorter. Differential strain in the segments during the passive portion of
      the cycle may be caused by differential joint excursions at the knee and hip
      acting on the ends of the muscle and being transmitted differentially by the
      passive visco-elastic properties of the muscle. Alternatively, the differential
      passive strain could be due to the action of active or passive muscles in the
      thigh that transmit force to the IPLO in shear. Based on basic sarcomere dynamics
      we predict that differential strain is more likely to occur in muscles undergoing
      active lengthening at the beginning of contraction than those undergoing only
      shortening.

PMID- 21957103
TI  - Mechanisms producing coordinated function across the breadth of a large
      biarticular thigh muscle.
AB  - We examined the hypothesis that structural features of the iliotibialis lateralis
      pars postacetabularis (ILPO) in guinea fowl allow this large muscle to maintain
      equivalent function along its anterior-posterior axis. The ILPO, the largest
      muscle in the hindlimb of the guinea fowl, is a hip and knee extensor. The
      fascicles of the ILPO originate across a broad region of the ilium and ischium
      posterior to the hip. Its long posterior fascicles span the length of the thigh
      and insert directly on the patellar tendon complex. However, its anterior
      fascicles are shorter and insert on a narrow aponeurosis that forms a tendinous
      band along the anterior edge of the muscle and is connected distally to the
      patellar tendon. The biarticular ILPO is actively lengthened and then actively
      shortened during stance. The moment arm of the fascicles at the hip increases
      along the anterior to posterior axis, whereas the moment arm at the knee is
      constant for all fascicles. Using electromyography and sonomicrometry, we
      examined the activity and strain of posterior and anterior fascicles of the ILPO.
      The activation was not significantly different in the anterior and posterior
      fascicles. Although we found significant differences in active lengthening and
      shortening strain between the anterior and posterior fascicles, the differences
      were small. The majority of shortening strain is caused by hip extension and the
      inverse relationship between hip moment arm and fascicle length along the
      anterior-posterior axis was found to have a major role in ensuring similar
      shortening strain. However, because the knee moment arm is the same for all
      fascicles, knee flexion in early stance was predicted to produce much larger
      lengthening strains in the short anterior fascicles than our measured values at
      this location. We propose that active lengthening of the anterior fascicles was
      lower than predicted because the aponeurotic tendon of insertion of the anterior
      fascicles was stretched and only a portion of the lengthening had to be
      accommodated by the active muscle fascicles.

PMID- 21957105
TI  - Cues to body size in the formant spacing of male koala (Phascolarctos cinereus)
      bellows: honesty in an exaggerated trait.
AB  - Determining the information content of vocal signals and understanding
      morphological modifications of vocal anatomy are key steps towards revealing the
      selection pressures acting on a given species' vocal communication system. Here,
      we used a combination of acoustic and anatomical data to investigate whether male
      koala bellows provide reliable information on the caller's body size, and to
      confirm whether male koalas have a permanently descended larynx. Our results
      indicate that the spectral prominences of male koala bellows are formants (vocal
      tract resonances), and show that larger males have lower formant spacing. In
      contrast, no relationship between body size and the fundamental frequency was
      found. Anatomical investigations revealed that male koalas have a permanently
      descended larynx: the first example of this in a marsupial. Furthermore, we found
      a deeply anchored sternothyroid muscle that could allow male koalas to retract
      their larynx into the thorax. While this would explain the low formant spacing of
      the exhalation and initial inhalation phases of male bellows, further research
      will be required to reveal the anatomical basis for the formant spacing of the
      later inhalation phases, which is predictive of vocal tract lengths of around 50
      cm (nearly the length of an adult koala's body). Taken together, these findings
      show that the formant spacing of male koala bellows has the potential to provide
      receivers with reliable information on the caller's body size, and reveal that
      vocal adaptations allowing callers to exaggerate (or maximise) the acoustic
      impression of their size have evolved independently in marsupials and placental
      mammals.

PMID- 21957104
TI  - Function of a large biarticular hip and knee extensor during walking and running
      in guinea fowl (Numida meleagris).
AB  - Physiological and anatomical evidence suggests that in birds the iliotibialis
      lateralis pars postacetabularis (ILPO) is functionally important for running.
      Incorporating regional information, we estimated the mean sarcomere strain
      trajectory and electromyographic (EMG) amplitude of the ILPO during level and
      incline walking and running. Using these data and data in the literature of
      muscle energy use, we examined three hypotheses: (1) active lengthening will
      occur on the ascending limb of the length-tension curve to avoid potential damage
      caused by stretch on the descending limb; (2) the active strain cycle will shift
      to favor active shortening when the birds run uphill and shortening will occur on
      the plateau and shallow ascending limb of the length-tension curve; and (3)
      measures of EMG intensity will correlate with energy use when the mechanical
      function of the muscle is similar. Supporting the first hypothesis, we found that
      the mean sarcomere lengths at the end of active lengthening during level
      locomotion were smaller than the predicted length at the start of the plateau of
      the length-tension curve. Supporting the second hypothesis, the magnitude of
      active lengthening decreased with increasing slope, whereas active shortening
      increased. In evaluating the relationship between EMG amplitude and energy use
      (hypothesis 3), we found that although increases in EMG intensity with speed,
      slope and loading were positively correlated with muscle energy use, the
      quantitative relationships between these variables differed greatly under
      different conditions. The relative changes in EMG intensity and energy use by the
      muscle probably varied because of changes in the mechanical function of the
      muscle that altered the ratio of muscle energy use to active muscle volume.
      Considering the overall function of the cycle of active lengthening and
      shortening of the fascicles of the ILPO, we conclude that the function of active
      lengthening is unlikely to be energy conservation and may instead be related to
      promoting stability at the knee. The work required to lengthen the ILPO during
      stance is provided by co-contracting knee flexors. We suggest that this
      potentially energetically expensive co-contraction serves to stabilize the knee
      in early stance by increasing the mechanical impedance of the joint.

PMID- 21957106
TI  - Principles underlying chromatophore addition during maturation in the European
      cuttlefish, Sepia officinalis.
AB  - The goal of this work was to identify some of the principles underlying
      chromatophore growth and development in the European cuttlefish, Sepia
      officinalis. One set of experiments used a regeneration model to follow the re
      growth of black chromatophores for 30 days following excision of a small piece of
      fin tissue. A separate set of experiments tracked and analyzed the addition of
      new fin chromatophores during a month of normal, undisturbed growth. We also
      followed the development of individual chromatophores from their initial
      appearance to full maturation to determine whether their color type was fixed.
      Based on the results of these studies, we propose five guiding principles for
      chromatophore growth and maturation. (1) The three chromatophore cell types-
      black, reddish-brown and yellow--are present at different spatial frequencies in
      the cuttlefish fin. (2) During normal growth, new chromatophores are inserted at
      a higher spatial frequency than existing (control) chromatophores of the same
      color type. (3) In regenerating tissue, new black chromatophores are initially
      added at low spatial frequencies. As regeneration continues, new black
      chromatophores appear at increasing spatial frequencies until they are inserted
      at a spatial frequency higher than that observed in control tissue, similar to
      the way in which chromatophores were observed to be added in normally growing
      tissue. (4) All chromatophores first appear as pale orange cells and slowly
      darken into their respective color types without passing through intermediate
      color stages. (5) New black chromatophores undergo a doubling in size as they
      mature, while reddish-brown and yellow chromatophores do not grow at all after
      they are inserted in the dermis.

PMID- 21957107
TI  - Biomechanics of octopedal locomotion: kinematic and kinetic analysis of the
      spider Grammostola mollicoma.
AB  - Despite the abundance of octapodal species and their evolutionary importance in
      originating terrestrial locomotion, the locomotion mechanics of spiders has
      received little attention so far. In this investigation we use inverse dynamics
      to study the locomotor performance of Grammostola mollicoma (18 g). Through 3-D
      kinematic measurements, the trajectory of the eight limbs and cephalothorax or
      abdomen allowed us to estimate the motion of the body centre of mass (COM) at
      different speeds. Classic mechanics of locomotion and multivariate analysis of
      several variables such as stride length and frequency, duty factor, mechanical
      external work and energy recovery, helped to identify two main gaits, a slow
      (speed <11 cm s(-1)) one and a fast one characterised by distinctive 3-D
      trajectories of COM. The total mechanical work (external + internal) calculated
      in the present study and metabolic data from the literature allowed us to
      estimate the locomotion efficiency of this species, which was less than 4%. Gait
      pattern due to alternating limb support, which generates asymmetrical COM
      trajectories and a small but consistent energy transfer between potential and
      kinetic energies of COM, is discussed both in terms of coordination indices and
      by referring to the octopod as formed by two quadrupeds in series. Analogies and
      differences of the newly obtained parameters with the allometric data and
      predictions are also illustrated.

PMID- 21957108
TI  - Salt stress alters fluid and ion transport by Malpighian tubules of Drosophila
      melanogaster: evidence for phenotypic plasticity.
AB  - Drosophila are tolerant of high levels of dietary salt and can provide a useful
      model for studies of the physiology of salt stress. The effects of NaCl- and KCl
      rich diets on haemolymph ionoregulation and Malpighian tubule (MT) fluid
      secretion, Na(+) and K(+) secretion and transepithelial potential were examined
      in larval and adult Drosophila melanogaster. K(+) concentrations in the
      haemolymph of adults reared on the KCl-rich (0.4 mol l(-1)) diet did not differ
      from the values for insects reared on the control diet. In the haemolymph of
      larvae reared on the K-rich diet, K(+) concentrations increased from 23 to 75
      mmol l(-1) after 6 h, then returned to the control value within 48 h. Na(+)
      concentrations in the haemolymph of adults or larvae reared for 1-7 days on the
      NaCl-rich (0.4 mol l(-1)) diet increased by ~50% relative to values for insects
      reared on the control diet. Rates of secretion of fluid, Na(+) and K(+) by MTs
      isolated from larvae reared on the Na-rich diet for >6 h and bathed in control
      saline containing 20 mmol l(-1) K(+) did not differ from the values for tubules
      of larvae reared on the control diet. Evidence of phenotypic plasticity was seen
      in the response of MTs isolated from larvae reared on the K-rich diet for >6 h
      and bathed in saline containing 60 mmol l(-1) K(+); secretion of fluid and K(+)
      increased by >50% relative to the values for tubules of larvae reared on the
      control diet. Secretion of fluid, Na(+) and K(+) increased when tubules were
      bathed in haemolymph collected from larvae reared on the Na- or K-rich diets.
      Secretion was further increased by addition of exogenous cAMP but not by addition
      of thapsigargin to the haemolymph. The results show that haemolymph
      ionoregulation in larvae reared on salt-rich diets involves both alterations in
      the basal secretion rates of Na(+) and/or K(+) as well as stimulatory effects of
      diuretic factors present in the haemolymph. The results suggest that such factors
      stimulate tubule fluid and ion secretion through increases in intracellular
      Ca(2+) in response to salt stress.

PMID- 21957109
TI  - Femoral loading mechanics in the Virginia opossum, Didelphis virginiana: torsion
      and mediolateral bending in mammalian locomotion.
AB  - Studies of limb bone loading in terrestrial mammals have typically found
      anteroposterior bending to be the primary loading regime, with torsion
      contributing minimally. However, previous studies have focused on large,
      cursorial eutherian species in which the limbs are held essentially upright.
      Recent in vivo strain data from the Virginia opossum (Didelphis virginiana), a
      marsupial that uses a crouched rather than an upright limb posture, have
      indicated that its femur experiences appreciable torsion during locomotion as
      well as strong mediolateral bending. The elevated femoral torsion and strong
      mediolateral bending observed in D. virginiana might result from external forces
      such as a medial inclination of the ground reaction force (GRF), internal forces
      deriving from a crouched limb posture, or a combination of these factors. To
      evaluate the mechanism underlying the loading regime of opossum femora, we filmed
      D. virginiana running over a force platform, allowing us to measure the magnitude
      of the GRF and its three-dimensional orientation relative to the limb,
      facilitating estimates of limb bone stresses. This three-dimensional analysis
      also allows evaluations of muscular forces, particularly those of hip adductor
      muscles, in the appropriate anatomical plane to a greater degree than previous
      two-dimensional analyses. At peak GRF and stress magnitudes, the GRF is oriented
      nearly vertically, inducing a strong abductor moment at the hip that is countered
      by adductor muscles on the medial aspect of the femur that place this surface in
      compression and induce mediolateral bending, corroborating and explaining loading
      patterns that were identified in strain analyses. The crouched orientation of the
      femur during stance in opossums also contributes to levels of femoral torsion as
      high as those seen in many reptilian taxa. Femoral safety factors were as high as
      those of non-avian reptiles and greater than those of upright, cursorial mammals,
      primarily because the load magnitudes experienced by opossums are lower than
      those of most mammals. Thus, the evolutionary transition from crouched to upright
      posture in mammalian ancestors may have been accompanied by an increase in limb
      bone load magnitudes.

PMID- 21957110
TI  - Carotenoid intake does not affect immune-stimulated oxidative burst in
      greenfinches.
AB  - Carotenoid-based integument colouration is extremely widespread in the animal
      kingdom. It has been hypothesized that carotenoid colouration is used for
      communicating the health status of the bearers because carotenoids are efficient
      immunomodulators or antioxidants. However, the latter argument has been recently
      debated and the mechanisms by which carotenoids modulate immunity or oxidative
      balance are poorly known. We performed an experiment on wild-caught captive
      greenfinches, passerine birds with carotenoid-based plumage colouration, in order
      to test whether dietary carotenoid supplementation affects immune-stimulated
      oxidative burst of phagocytes in the whole blood and humoral immune response to a
      novel antigen, Brucella abortus (BA). Additionally, we tested whether immune
      stimulation with bacterial lipopolysaccharide (LPS) affects blood carotenoid
      levels. We thus tested the effects of carotenoids on the oxidative burst of
      phagocytes under neutral conditions and during in vivo immune challenge. LPS
      injection depleted plasma carotenoids, indicating involvement of these
      phytochemicals in the immune response. However, we did not find any evidence that
      manipulation of carotenoid intake had modulated anti-BA antibody production, LPS
      stimulated oxidative burst of phagocytes, or basal levels of circulating reactive
      oxygen species. This indicates that carotenoid intake does not affect endogenous
      production of reactive oxygen species by immune cells. This finding is consistent
      with the view that carotenoids are unlikely to provide a direct link between
      oxidative stress and colouration. However, it remains to be tested whether the
      oxidative burst of phagocytes induced in our experiment actually inflicts
      oxidative damage and whether carotenoids play a role in the attenuation of such
      potential damages.

PMID- 21957111
TI  - Pleated turtle escapes the box--shape changes in Dermochelys coriacea.
AB  - Typical chelonians have a rigid carapace and plastron that form a box-like
      structure that constrains several aspects of their physiology and ecology. The
      leatherback sea turtle, Dermochelys coriacea, has a flexible bony carapace
      strengthened by seven longitudinal ridges, whereas the plastron is reduced to an
      elliptical outer bony structure, so that the ventrum has no bony support.
      Measurements of the shell were made on adult female leatherbacks studied on the
      feeding grounds of waters off Nova Scotia (NS) and on breeding beaches of French
      Guiana (FG) to examine whether foraging and/or breeding turtles alter carapace
      size and/or shape. NS turtles exhibited greater mass and girth for a given curved
      carapace length (CCL) than FG turtles. Girth:CCL ratios rose during the feeding
      season, indicating increased girth. Measurements were made of the direct
      (straight) and surface (curved) distances between the medial longitudinal ridge
      and first right-hand longitudinal ridge (at 50% CCL). In NS turtles, the ratio of
      straight to curved inter-ridge distances was significantly higher than in FG
      turtles, indicating distension of the upper surfaces of the NS turtles between
      the ridges. FG females laid 11 clutches in the breeding season; although CCL and
      curved carapace width remained stable, girth declined between each nesting
      episode, indicating loss of mass. Straight to curved inter-ridge distance ratios
      did not change significantly during the breeding season, indicating loss of
      dorsal blubber before the onset of breeding. The results demonstrate substantial
      alterations in size and shape of female D. coriacea over periods of weeks to
      months in response to alterations in nutritional and reproductive status.

PMID- 21957112
TI  - Moment-to-moment flight manoeuvres of the female yellow fever mosquito (Aedes
      aegypti L.) in response to plumes of carbon dioxide and human skin odour.
AB  - Odours are crucial cues enabling female mosquitoes to orient to prospective
      hosts. However, their in-flight manoeuvres to host odours are virtually unknown.
      Here we analyzed in 3-D the video records of female Aedes aegypti mosquitoes
      flying in a wind tunnel in response to host odour plumes that differed in spatial
      structure and composition. Following a brief (~0.03 s) encounter with CO(2),
      mosquitoes surged upwind and, in the absence of further encounters, counterturned
      without displacing upwind. These patterns resemble moth responses to encounter
      and loss of a filament of pheromone. Moreover, CO(2) encounters induced a highly
      regular pattern of counterturning across the windline in the horizontal
      (crosswind) and vertical planes, causing the mosquito to transect repeatedly the
      area where CO(2) was previously detected. However, despite the rapid changes
      across all three axes following an encounter with CO(2), the angular velocities
      remained remarkably constant. This suggests that during these CO(2)-induced
      surges mosquitoes stabilize flight through sensors, such as the halteres and
      Johnston organs, sensitive to Coriolis forces. In contrast to the instantaneous
      responses of the mosquito CO(2), a brief encounter with a filament of human skin
      odour did not induce a consistent change in mosquito flight. These differential
      responses were reflected in further experiments with broad plumes. A broad
      homogeneous plume of skin odour induced rapid upwind flight and source finding,
      whereas a broad filamentous plume of skin odour lowered activation rates, kinetic
      responses and source finding compared with homogeneous plumes. Apparently, yellow
      fever mosquitoes need longer continuous exposure to complex skin-odour blends to
      induce activation and source finding.

PMID- 21957113
TI  - Effect of cuticular abrasion and recovery on water loss rates in queens of the
      desert harvester ant Messor pergandei.
AB  - Factors that affect water loss rates (WLRs) are poorly known for organisms in
      natural habitats. Seed-harvester ant queens provide an ideal system for examining
      such factors because WLRs for mated queens excavated from their incipient nests
      are twofold to threefold higher than those of alate queens. Indirect data suggest
      that this increase results from soil particles abrading the cuticle during nest
      excavation. This study provides direct support for the cuticle abrasion
      hypothesis by measuring total mass-specific WLRs, cuticular abrasion, cuticular
      transpiration, respiratory water loss and metabolic rate for queens of the ant
      Messor pergandei at three stages: unmated alate queens, newly mated dealate
      queens (undug foundresses) and mated queens excavated from their incipient nest
      (dug foundresses); in addition we examined these processes in artificially
      abraded alate queens. Alate queens had low WLRs and low levels of cuticle
      abrasion, whereas dug foundresses had high WLRs and high levels of cuticle
      abrasion. Total WLR and cuticular transpiration were lowest for alate queens,
      intermediate for undug foundresses and highest for dug foundresses. Respiratory
      water loss contributed ~10% of the total WLR and was lower for alate queens and
      undug foundresses than for dug foundresses. Metabolic rate did not vary across
      stages. Total WLR and cuticular transpiration of artificially abraded alate
      queens increased, whereas respiratory water loss and metabolic rate were
      unaffected. Overall, increased cuticular transpiration accounted for essentially
      all the increased total water loss in undug and dug foundresses and artificially
      abraded queens. Artificially abraded queens and dug foundresses showed partial
      recovery after 14 days.

PMID- 21957115
TI  - Survey to determine the seroprevalence of Toxoplasma gondii infection in British
      sheep flocks.
AB  - A serological survey of Toxoplasma gondii infection in adult breeding sheep in
      Great Britain was conducted using surplus sera taken during a seroprevalence
      study of Brucella melitensis in 2009. Of the 3539 sera collected from 227 flocks,
      2619 (74 per cent) were found to be positive for T gondii specific antibody when
      tested using latex agglutination. Multilevel logistic modelling suggested that
      the likelihood of infection increased with age and this effect appeared to be
      amplified in animals vaccinated against T gondii. The model also indicated that
      the odds of sheep being seropositive were increased on premises where cattle were
      also kept. These results suggest a high level of Toxoplasma infection in breeding
      sheep in Great Britain and provide further evidence to suggest that postnatal
      infection is more common than congenital infection in sheep.

PMID- 21957114
TI  - Curative effect of topical treatment of digital dermatitis with a gel containing
      activated copper and zinc chelate.
AB  - The efficacy of two topical treatments for painful ulcerative stage (M2) of
      bovine digital dermatitis (BDD) lesions was compared in a clinical trial
      conducted on five dairy farms in 2009 to 2010. The first treatment was a water
      based gel with active components copper and zinc (Intra Hoof-fit gel [IHF]) and
      the second treatment was a topical chlortetracycline spray (CTC spray). The
      experimental unit for this study was the hindleg with the presence of a BDD
      lesion. Cure was defined as the transition of an M2 lesion into a healed (M0) or
      a non-painful chronic stage (M4) of BDD at D28. On day 0, cows with M2 BDD
      lesions were photographed and were treated with either IHF or CTC. Subsequently,
      feet were photographed and scored on D28. The cure rate of M2 BDD lesions treated
      with IHF at D28 was 0.92 (CI 0.84 to 0.96) and was significantly better than for
      M2 BDD lesions treated with CTC, which was 0.58 (CI 0.47 to 0.68).

PMID- 21957116
TI  - Modulating protein adsorption onto hydroxyapatite particles using different amino
      acid treatments.
AB  - Hydroxyapatite (HA) is a material of choice for bone grafts owing to its chemical
      and structural similarities to the mineral phase of hard tissues. The combination
      of osteogenic proteins with HA materials that carry and deliver the proteins to
      the bone-defective areas will accelerate bone regeneration. The study
      investigated the treatment of HA particles with different amino acids such as
      serine (Ser), asparagine (Asn), aspartic acid (Asp) and arginine (Arg) to enhance
      the adsorption ability of HA carrier for delivering therapeutic proteins to the
      body. The crystallinity of HA reduced when amino acids were added during HA
      preparation. Depending on the types of amino acid, the specific surface area of
      the amino acid-functionalized HA particles varied from 105 to 149 m(2) g(-1).
      Bovine serum albumin (BSA) and lysozyme were used as model proteins for
      adsorption study. The protein adsorption onto the surface of amino acid
      functionalized HA depended on the polarities of HA particles, whereby, compared
      with lysozyme, BSA demonstrated higher affinity towards positively charged Arg
      HA. Alternatively, the binding affinity of lysozyme onto the negatively charged
      Asp-HA was higher when compared with BSA. The BSA and lysozyme adsorptions onto
      the amino acid-functionalized HA fitted better into the Freundlich than Langmuir
      model. The amino acid-functionalized HA particles that had higher protein
      adsorption demonstrated a lower protein-release rate.

PMID- 21957117
TI  - Statistical wall shear stress maps of ruptured and unruptured middle cerebral
      artery aneurysms.
AB  - Haemodynamics and morphology play an important role in the genesis, growth and
      rupture of cerebral aneurysms. The goal of this study was to generate and analyse
      statistical wall shear stress (WSS) distributions and shapes in middle cerebral
      artery (MCA) saccular aneurysms. Unsteady flow was simulated in seven ruptured
      and 15 unruptured MCA aneurysms. In order to compare these results, all
      geometries must be brought in a uniform coordinate system. For this, aneurysms
      with corresponding WSS data were transformed into a uniform spherical shape;
      then, all geometries were uniformly aligned in three-dimensional space.
      Subsequently, we compared statistical WSS maps and surfaces of ruptured and
      unruptured aneurysms. No significant (p > 0.05) differences exist between
      ruptured and unruptured aneurysms regarding radius and mean WSS. In unruptured
      aneurysms, statistical WSS map relates regions with high (greater than 3 Pa) WSS
      to the neck region. In ruptured aneurysms, additional areas with high WSS
      contiguous to regions of low (less than 1 Pa) WSS are found in the dome region.
      In ruptured aneurysms, we found significantly lower WSS. The averaged aneurysm
      surface of unruptured aneurysms is round shaped, whereas the averaged surface of
      ruptured cases is multi-lobular. Our results confirm the hypothesis of low WSS
      and irregular shape as the essential rupture risk parameters.

PMID- 21957118
TI  - Using causal models to distinguish between neurogenesis-dependent and 
      independent effects on behaviour.
AB  - There has been a substantial amount of research on the relationship between
      hippocampal neurogenesis and behaviour over the past 15 years, but the causal
      role that new neurons have on cognitive and affective behavioural tasks is still
      far from clear. This is partly due to the difficulty of manipulating levels of
      neurogenesis without inducing off-target effects, which might also influence
      behaviour. In addition, the analytical methods typically used do not directly
      test whether neurogenesis mediates the effect of an intervention on behaviour.
      Previous studies may have incorrectly attributed changes in behavioural
      performance to neurogenesis because the role of known (or unknown) neurogenesis
      independent mechanisms was not formally taken into consideration during the
      analysis. Causal models can tease apart complex causal relationships and were
      used to demonstrate that the effect of exercise on pattern separation is via
      neurogenesis-independent mechanisms. Many studies in the neurogenesis literature
      would benefit from the use of statistical methods that can separate neurogenesis
      dependent from neurogenesis-independent effects on behaviour.

PMID- 21957119
TI  - Pressurized vascular systems for self-healing materials.
AB  - An emerging strategy for creating self-healing materials relies on embedded
      vascular networks of microchannels to transport reactive fluids to regions of
      damage. Here we investigate the use of active pumping for the pressurized
      delivery of a two-part healing system, allowing a small vascular system to
      deliver large volumes of healing agent. Different pumping strategies are explored
      to improve the mixing and subsequent polymerization of healing agents in the
      damage zone. Significant improvements in the number of healing cycles and in the
      overall healing efficiency are achieved compared with prior passive schemes that
      use only capillary forces for the delivery of healing agents. At the same time,
      the volume of the vascular system required to achieve this superior healing
      performance is significantly reduced. In the best case, nearly full recovery of
      fracture toughness is attained throughout 15 cycles of damage and healing, with a
      vascular network constituting just 0.1 vol% of the specimen.

PMID- 21957120
TI  - An X-ray and neutron reflectometry study of 'PEG-like' plasma polymer films.
AB  - Plasma-enhanced chemical vapour-deposited films of di(ethylene glycol) dimethyl
      ether were analysed by a combination of X-ray photoelectron spectroscopy, atomic
      force microscopy, quartz crystal microbalance with dissipation monitoring (QCM
      D), X-ray and neutron reflectometry (NR). The combination of these techniques
      enabled a systematic study of the impact of plasma deposition conditions upon
      resulting film chemistry (empirical formula), mass densities, structure and water
      solvation, which has been correlated with the films' efficacy against protein
      fouling. All films were shown to contain substantially less hydrogen than the
      original monomer and absorb a vast amount of water, which correlated with their
      mass density profiles. A proportion of the plasma polymer hydrogen atoms were
      shown to be exchangeable, while QCM-D measurements were inaccurate in detecting
      associated water in lower power films that contained loosely bound material. The
      higher protein resistance of the films deposited at a low load power was
      attributed to its greater chemical and structural similarity to that of
      poly(ethylene glycol) graft surfaces. These studies demonstrate the utility of
      using X-ray and NR analysis techniques in furthering the understanding of the
      chemistry of these films and their interaction with water and proteins.

PMID- 21957122
TI  - The European Journal of Endocrinology: changing of the guard.

PMID- 21957121
TI  - In-roads to the spread of antibiotic resistance: regional patterns of microbial
      transmission in northern coastal Ecuador.
AB  - The evolution of antibiotic resistance (AR) increases treatment cost and
      probability of failure, threatening human health worldwide. The relative
      importance of individual antibiotic use, environmental transmission and rates of
      introduction of resistant bacteria in explaining community AR patterns is poorly
      understood. Evaluating their relative importance requires studying a region where
      they vary. The construction of a new road in a previously roadless area of
      northern coastal Ecuador provides a valuable natural experiment to study how
      changes in the social and natural environment affect the epidemiology of
      resistant Escherichia coli. We conducted seven bi-annual 15 day surveys of AR
      between 2003 and 2008 in 21 villages. Resistance to both ampicillin and
      sulphamethoxazole was the most frequently observed profile, based on antibiogram
      tests of seven antibiotics from 2210 samples. The prevalence of enteric bacteria
      with this resistance pair in the less remote communities was 80 per cent higher
      than in more remote communities (OR = 1.8 [1.3, 2.3]). This pattern could not be
      explained with data on individual antibiotic use. We used a transmission model to
      help explain this observed discrepancy. The model analysis suggests that both
      transmission and the rate of introduction of resistant bacteria into communities
      may contribute to the observed regional scale AR patterns, and that village-level
      antibiotic use rate determines which of these two factors predominate. While
      usually conceived as a main effect on individual risk, antibiotic use rate is
      revealed in this analysis as an effect modifier with regard to community-level
      risk of resistance.

PMID- 21957123
TI  - A conserved region in the prM protein is a critical determinant in the assembly
      of flavivirus particles.
AB  - Flaviviruses are assembled to bud into the lumen of the endoplasmic reticulum
      (ER) and are secreted through the vesicle transport pathway, but the details of
      the molecular mechanism of virion assembly remain largely unknown. In this study,
      a highly conserved region in the prM protein was identified among flaviviruses.
      In the subviral particle (SP) system of tick-borne encephalitis virus (TBEV) and
      Japanese encephalitis virus, secretion of SPs was impaired by a mutation in the
      conserved region in the prM protein. Viral proteins were sparse in the Golgi
      complex and accumulated in the ER. Ultrastructural analysis revealed that long
      filamentous structures, rather than spherical SPs, were observed in the lumen of
      the ER as a result of the mutation. The production of infectious virions derived
      from infectious cDNA of TBEV was also reduced by mutations in the conserved
      region. Molecular modelling analysis suggested that the conserved region is
      important for the association of prM-envelope protein heterodimers in the
      formation of a spike of immature virion. These results are the first
      demonstration that the conserved region in the prM protein is a molecular
      determinant for the flavivirus assembly process.

PMID- 21957124
TI  - Viperin inhibits hepatitis C virus replication by interfering with binding of
      NS5A to host protein hVAP-33.
AB  - Viperin is a type-I and -II interferon-inducible intracytoplasmic protein that
      mediates antiviral activity against several viruses. A previous study has
      reported that viperin could limit hepatitis C virus (HCV) replication in vitro.
      However, the underlying mechanism remains elusive. In the present study, we found
      that overexpression of viperin could inhibit HCV replication in a dose-dependent
      manner in both the replicon and HCVcc systems. Furthermore, through co
      immunoprecipitation and laser confocal microscopic analysis, viperin was found to
      interact with the host protein hVAP-33. Mutagenesis analysis demonstrated that
      the anti-HCV activity of viperin was located to its C terminus, which was
      required for the interaction with the C-terminal domain of hVAP-33. Competitive
      co-immunoprecipitation analysis showed that viperin could interact competitively
      with hVAP-33, and could therefore interfere with its interactions with HCV NS5A.
      In summary, these findings suggest a novel mechanism by which viperin inhibits
      HCV replication, possibly through binding to host protein hVAP-33 and interfering
      with its interaction with NS5A.

PMID- 21957125
TI  - Novel virus-encoded microRNA molecules expressed by ovine herpesvirus 2
      immortalized bovine T-cells.
AB  - A number of herpesviruses have now been shown to encode microRNAs (miRNAs) that
      have roles in control of both viral and cellular gene expression. Ovine
      herpesvirus 2 (OvHV-2) is the causative agent of sheep-associated malignant
      catarrhal fever, a fatal lymphoproliferative disease of cattle. Using massively
      parallel sequencing and Northern hybridization we have identified eight putative
      miRNAs encoded by OvHV-2 expressed in an OvHV-2-immortalized bovine lymphocyte
      cell line. These eight miRNAs are encoded in two areas of the OvHV-2 genome that
      contain no predicted protein coding regions and show no sequence similarity with
      other herpesvirus or cellular miRNAs. This represents the first report of the
      expression of virally encoded miRNAs in the genus Macavirus of herpesviruses.

PMID- 21957126
TI  - Residues in domain III of the dengue virus envelope glycoprotein involved in cell
      surface glycosaminoglycan binding.
AB  - The dengue virus (DENV) envelope (E) protein mediates virus entry into cells via
      interaction with a range of cell-surface receptor molecules. Cell-surface
      glycosaminoglycans (GAGs) have been shown to play an early role in this
      interaction, and charged oligosaccharides such as heparin bind to the E protein.
      We have examined this interaction using site-directed mutagenesis of a
      recombinant form of the putative receptor-binding domain III of the DENV-2E
      protein expressed as an MBP (maltose-binding protein)-fusion protein. Using an
      ELISA-based GAG-binding assay, cell-based binding analysis and antiviral-activity
      assays, we have identified two critical residues, K291 and K295, that are
      involved in GAG interactions. These studies have also demonstrated differential
      binding between mosquito and human cells.

PMID- 21957127
TI  - Annexin A1 regulates neutrophil clearance by macrophages in the mouse bone
      marrow.
AB  - Under homeostatic conditions, a proportion of senescent CXCR4(hi) neutrophils
      home from the circulation back to the bone marrow, where they are phagocytosed by
      bone marrow macrophages. In this study, we have identified an unexpected role for
      the anti-inflammatory molecule annexin A1 (AnxA1) as a critical regulator of this
      process. We first observed that AnxA1(-/-) mice have significantly increased
      neutrophil numbers in their bone marrow while having normal levels of GM and G
      colony-forming units, monocytes, and macrophages. Although AnxA1(-/-) mice have
      more neutrophils in the bone marrow, a greater proportion of these cells are
      senescent, as determined by their higher levels of CXCR4 expression and annexin V
      binding. Consequently, bone marrow neutrophils from AnxA1(-/-) mice exhibit a
      reduced migratory capacity in vitro. Studies conducted in vitro also show that
      expression of AnxA1 is required for bone marrow macrophages, but not peritoneal
      macrophages, to phagocytose apoptotic neutrophils. Moreover, in vivo experiments
      indicate a defect in clearance of wild-type neutrophils in the bone marrow of
      AnxA1(-/-) mice. Thus, we conclude that expression of AnxA1 by resident
      macrophages is a critical determinant for neutrophil clearance in the bone
      marrow.

PMID- 21957128
TI  - Cardiac dysfunction and impaired compensatory response to pressure overload in
      mice deficient in stem cell antigen-1.
AB  - Stem cell antigen-1 (Sca-1) has been used to identify cardiac stem cells in the
      mouse heart. To investigate the function of Sca-1 in aging and during the cardiac
      adaptation to stress, we used Sca-1-deficient mice. These mice developed dilated
      cardiomyopathy [end-diastolic left ventricular diameter at 18 wk of age: wild
      type (WT) mice, 4.2 mm +/- 0.3; Sca-1-knockout (Sca-1-KO) mice, 4.6 mm +/- 0.1;
      ejection fraction: WT mice, 51.1 +/- 2.7%; Sca-1-KO mice, 42.9 +/- 2.7%].
      Furthermore, the hearts of mice lacking Sca-1 demonstrated exacerbated
      susceptibility to pressure overload [ejection fraction after transaortic
      constriction (TAC): WT mice, 43.5 +/- 3.2%; Sca-1-KO mice, 30.8% +/- 4.0] and
      increased apoptosis, as shown by the 2.5-fold increase in TUNEL(+) cells in Sca-1
      deficient hearts under stress. Sca-1 deficiency affected primarily the nonmyocyte
      cell fraction. Indeed, the number of Nkx2.5(+) nonmyocyte cells, which represent
      a population of cardiac precursor cells (CPCs), was 2-fold smaller in Sca-1
      deficient neonatal hearts. In vitro, the ability of CPCs to differentiate into
      cardiomyocytes was not affected by Sca-1 deletion. In contrast, these cells
      demonstrated unrestricted differentiation into cardiomyocytes. Interestingly,
      proliferation of cardiac nonmyocyte cells in response to stress, as judged by
      BrdU incorporation, was higher in mice lacking Sca-1 (percentages of BrdU(+)
      cells in the heart after TAC: WT mice, 4.4 +/- 2.1%; Sca-1-KO mice, 19.3 +/-
      4.2%). These data demonstrate the crucial role of Sca-1 in the maintenance of
      cardiac integrity and suggest that Sca-1 restrains spontaneous differentiation in
      the precursor population. The absence of Sca-1 results in uncontrolled precursor
      recruitment, exhaustion of the precursor pool, and cardiac dysfunction.

PMID- 21957129
TI  - Opposed regulation of type I IFN-induced STAT3 and ISGF3 transcriptional
      activities by histone deacetylases (HDACS) 1 and 2.
AB  - The antiviral and antiproliferative responses mediated by type I interferons
      (IFNs) depend on JAK/STAT signaling and ISGF3 (STAT1:STAT2:IRF9)-dependent
      transcription. In addition, type I IFNs stimulate STAT3 activation in many cell
      types, an event generally associated with cell cycle progression, survival, and
      proliferation. To gather more insight into this functionally contradictive
      phenomenon, we studied the regulation of STAT3 transcriptional activity upon type
      I IFN treatment. We show that IFNalpha2 stimulation strongly induces STAT3
      phosphorylation, nuclear translocation, and promoter binding, yet the activation
      of transcription of a STAT3-dependent reporter and endogenous genes, such as
      SOCS3 and c-FOS, is impaired. Simultaneous treatment with IFNalpha2 and
      trichostatin A, as well as combined HDAC1/HDAC2 silencing, restores STAT3
      dependent reporter gene and endogenous gene expression, strongly suggesting that
      HDAC1 and HDAC2 are directly involved in repressing IFNalpha2-activated STAT3. Of
      note, single silencing of only one of the two HDACs does not lead to enhanced
      STAT3 activity, supporting a functional redundancy between these two enzymes. In
      sharp contrast, HDAC1 and HDAC2 activities are required for ISGF3-dependent gene
      expression. We conclude that HDAC1 and HDAC2 differentially modulate STAT
      activity in response to IFNalpha2: while they are required for the induction of
      ISGF3-responsive genes, they impair the transcription of STAT3-dependent genes.

PMID- 21957130
TI  - The evolution of sex differences in mate searching when females benefit: new
      theory and a comparative test.
AB  - Sexual selection is thought to have led to searching as a profitable, but risky
      way of males obtaining mates. While there is great variation in which sex
      searches, previous theory has not considered search evolution when both males and
      females benefit from multiple mating. We present new theory and link it with data
      to bridge this gap. Two different search protocols exist between species in the
      bush-cricket genus Poecilimon (Orthoptera): females search for calling males, or
      males search for calling females. Poecilimon males also transfer a costly nuptial
      food gift to their mates during mating. We relate variations in searching
      protocols to variation in nuptial gift size among 32 Poecilimon taxa. As
      predicted, taxa where females search produce significantly larger nuptial gifts
      than those where males search. Our model and results show that search roles can
      reverse when multiple mating brings about sufficiently strong material benefits
      to females.

PMID- 21957131
TI  - The original colours of fossil beetles.
AB  - Structural colours, the most intense, reflective and pure colours in nature, are
      generated when light is scattered by complex nanostructures. Metallic structural
      colours are widespread among modern insects and can be preserved in their fossil
      counterparts, but it is unclear whether the colours have been altered during
      fossilization, and whether the absence of colours is always real. To resolve
      these issues, we investigated fossil beetles from five Cenozoic biotas. Metallic
      colours in these specimens are generated by an epicuticular multi-layer
      reflector; the fidelity of its preservation correlates with that of other key
      cuticular ultrastructures. Where these other ultrastructures are well preserved
      in non-metallic fossil specimens, we can infer that the original cuticle lacked a
      multi-layer reflector; its absence in the fossil is not a preservational
      artefact. Reconstructions of the original colours of the fossils based on the
      structure of the multi-layer reflector show that the preserved colours are offset
      systematically to longer wavelengths; this probably reflects alteration of the
      refractive index of the epicuticle during fossilization. These findings will
      allow the former presence, and original hue, of metallic structural colours to be
      identified in diverse fossil insects, thus providing critical evidence of the
      evolution of structural colour in this group.

PMID- 21957132
TI  - Risky movement increases the rate of range expansion.
AB  - The movement rules used by an individual determine both its survival and
      dispersal success. Here, we develop a simple model that links inter-patch
      movement behaviour with population dynamics in order to explore how individual
      dispersal behaviour influences not only its dispersal and survival, but also the
      population's rate of range expansion. Whereas dispersers are most likely to
      survive when they follow nearly straight lines and rapidly orient movement
      towards a non-natal patch, the most rapid rates of range expansion are obtained
      for trajectories in which individuals delay biasing their movement towards a non
      natal patch. This result is robust to the spatial structure of the landscape.
      Importantly, in a set of evolutionary simulations, we also demonstrate that the
      movement strategy that evolves at an expanding front is much closer to that
      maximizing the rate of range expansion than that which maximizes the survival of
      dispersers. Our results suggest that if one of our conservation goals is the
      facilitation of range-shifting, then current indices of connectivity need to be
      complemented by the development and utilization of new indices providing a
      measure of the ease with which a species spreads across a landscape.

PMID- 21957133
TI  - What causes intraspecific variation in resting metabolic rate and what are its
      ecological consequences?
AB  - Individual differences in the energy cost of self-maintenance (resting metabolic
      rate, RMR) are substantial and the focus of an emerging research area. These
      differences may influence fitness because self-maintenance is considered as a
      life-history component along with growth and reproduction. In this review, we ask
      why do some individuals have two to three times the 'maintenance costs' of
      conspecifics, and what are the fitness consequences? Using evidence from a range
      of species, we demonstrate that diverse factors, such as genotypes, maternal
      effects, early developmental conditions and personality differences contribute to
      variation in individual RMR. We review evidence that RMR is linked with fitness,
      showing correlations with traits such as growth and survival. However, these
      relationships are modulated by environmental conditions (e.g. food supply),
      suggesting that the fitness consequences of a given RMR may be context-dependent.
      Then, using empirical examples, we discuss broad-scale reasons why variation in
      RMR might persist in natural populations, including the role of both spatial and
      temporal variation in selection pressures and trans-generational effects. To
      conclude, we discuss experimental approaches that will enable more rigorous
      examination of the causes and consequences of individual variation in this key
      physiological trait.

PMID- 21957134
TI  - Muscle power attenuation by tendon during energy dissipation.
AB  - An important function of skeletal muscle is deceleration via active muscle
      fascicle lengthening, which dissipates movement energy. The mechanical interplay
      between muscle contraction and tendon elasticity is critical when muscles produce
      energy. However, the role of tendon elasticity during muscular energy dissipation
      remains unknown. We tested the hypothesis that tendon elasticity functions as a
      mechanical buffer, preventing high (and probably damaging) velocities and powers
      during active muscle fascicle lengthening. We directly measured lateral
      gastrocnemius muscle force and length in wild turkeys during controlled landings
      requiring rapid energy dissipation. Muscle-tendon unit (MTU) strain was measured
      via video kinematics, independent of muscle fascicle strain (measured via
      sonomicrometry). We found that rapid MTU lengthening immediately following impact
      involved little or no muscle fascicle lengthening. Therefore, joint flexion had
      to be accommodated by tendon stretch. After the early contact period, muscle
      fascicles lengthened and absorbed energy. This late lengthening occurred after
      most of the joint flexion, and was thus mainly driven by tendon recoil. Temporary
      tendon energy storage led to a significant reduction in muscle fascicle
      lengthening velocity and the rate of energy absorption. We conclude that tendons
      function as power attenuators that probably protect muscles against damage from
      rapid and forceful lengthening during energy dissipation.

PMID- 21957135
TI  - Widespread genetic linkage of mating signals and preferences in the Hawaiian
      cricket Laupala.
AB  - The evolution of novel sexual communication systems is integral to the process of
      speciation, as it discourages gene flow between incipient species. Physical
      linkage between genes underlying male-female communication (i.e. sexual signals
      and preferences for them) facilitates both rapid and coordinated divergence of
      sexual communication systems between populations and reduces recombination in the
      face of occasional hybridization between diverging populations. Despite these
      ramifications of the genetic architecture of sexual communication for sexual
      selection and speciation, few studies have examined this relationship
      empirically. Previous studies of the closely related Hawaiian crickets Laupala
      paranigra and Laupala kohalensis have indirectly suggested that many of the genes
      underlying the difference in pulse rate of male song are physically linked with
      genes underlying the difference in female preference for pulse rate. Using marker
      assisted introgression, we moved 'slow pulse rate' alleles from L. paranigra at
      five known quantitative trait loci (QTL) underlying male pulse rate into the
      'fast pulse rate' genetic background of L. kohalensis and assessed the effect of
      these loci on female preference. An astounding four out of five song QTL
      predicted the preferences of female fourth-generation backcrosses, providing
      direct evidence for the extensive genetic linkage of song and preference in one
      of the fastest diversifying genera currently known.

PMID- 21957136
TI  - When mothers make sons sexy: maternal effects contribute to the increased sexual
      attractiveness of extra-pair offspring.
AB  - Quality differences between offspring sired by the social and by an extra-pair
      partner are usually assumed to have a genetic basis, reflecting genetic benefits
      of female extra-pair mate choice. In the zebra finch (Taeniopygia guttata), we
      identified a colour ornament that is under sexual selection and appears to have a
      heritable basis. Hence, by engaging in extra-pair copulations with highly
      ornamented males, females could, in theory, obtain genes for increased offspring
      attractiveness. Indeed, sons sired by extra-pair partners had larger ornaments,
      seemingly supporting the genetic benefit hypothesis. Yet, when comparing ornament
      size of the social and extra-pair partners, there was no difference. Hence, the
      observed differences most likely had an environmental basis, mediated, for
      example, via differential maternal investment of resources into the eggs
      fertilized by extra-pair and social partners. Such maternal effects may (at least
      partly) be mediated by egg size, which we found to be associated with mean
      ornament expression in sons. Our results are consistent with the idea that
      maternal effects can shape sexual selection by altering the genotype-phenotype
      relationship for ornamentation. They also caution against automatically
      attributing greater offspring attractiveness or viability to an extra-pair mate's
      superior genetic quality, as without controlling for differential maternal
      investment we may significantly overestimate the role of genetic benefits in the
      evolution of extra-pair mating behaviour.

PMID- 21957137
TI  - Constraints on the wing morphology of pterosaurs.
AB  - Animals that fly must be able to do so over a huge range of aerodynamic
      conditions, determined by weather, wind speed and the nature of their
      environment. No single parameter can be used to determine-let alone measure
      optimum flight performance as it relates to wing shape. Reconstructing the wings
      of the extinct pterosaurs has therefore proved especially problematic: these
      Mesozoic flying reptiles had a soft-tissue membranous flight surface that is
      rarely preserved in the fossil record. Here, we review basic mechanical and
      aerodynamic constraints that influenced the wing shape of pterosaurs, and,
      building on this, present a series of theoretical modelling results. These
      results allow us to predict the most likely wing shapes that could have been
      employed by these ancient reptiles, and further show that a combination of
      anterior sweep and a reflexed proximal wing section provides an aerodynamically
      balanced and efficient theoretical pterosaur wing shape, with clear benefits for
      their flight stability.

PMID- 21957138
TI  - Anomalous rise in algal production linked to lakewater calcium decline through
      food web interactions.
AB  - Increased algal blooms are a threat to aquatic ecosystems worldwide, although the
      combined effects of multiple stressors make it difficult to determine the
      underlying causes. We explore whether changes in trophic interactions in response
      to declining calcium (Ca) concentrations, a water quality issue only recently
      recognized in Europe and North America, can be linked with unexplained bloom
      production. Using a palaeolimnological approach analysing the remains of
      Cladocera (herbivorous grazers) and visual reflectance spectroscopically inferred
      chlorophyll a from the sediments of a Nova Scotia (Canada) lake, we show that a
      keystone grazer, Daphnia, declined in the early 1990s and was replaced by a less
      effective grazer, Bosmina, while inferred chlorophyll a levels tripled at
      constant total phosphorus (TP) concentrations. The decline in Daphnia cannot be
      attributed to changes in pH, thermal stratification or predation, but instead is
      linked to declining lakewater [Ca]. The consistency in the timing of changes in
      Daphnia and inferred chlorophyll a suggests top-down control on algal production,
      providing, to our knowledge, the first evidence of a link between lakewater [Ca]
      decline and elevated algal production mediated through the effects of [Ca]
      decline on Daphnia. [Ca] decline has severe implications for whole-lake food
      webs, and presents yet another mechanism for potential increases in algal blooms.

PMID- 21957139
TI  - Mycobacterial secretion systems ESX-1 and ESX-5 play distinct roles in host cell
      death and inflammasome activation.
AB  - During infection of humans and animals, pathogenic mycobacteria manipulate the
      host cell causing severe diseases such as tuberculosis and leprosy. To understand
      the basis of mycobacterial pathogenicity, it is crucial to identify the molecular
      virulence mechanisms. In this study, we address the contribution of ESX-1 and ESX
      5--two homologous type VII secretion systems of mycobacteria that secrete
      distinct sets of immune modulators--during the macrophage infection cycle. Using
      wild-type, ESX-1- and ESX-5-deficient mycobacterial strains, we demonstrate that
      these secretion systems differentially affect subcellular localization and
      macrophage cell responses. We show that in contrast to ESX-1, the effector
      proteins secreted by ESX-5 are not required for the translocation of
      Mycobacterium tuberculosis or Mycobacterium marinum to the cytosol of host cells.
      However, the M. marinum ESX-5 mutant does not induce inflammasome activation and
      IL-1beta activation. The ESX-5 system also induces a caspase-independent cell
      death after translocation has taken place. Importantly, by means of inhibitory
      agents and small interfering RNA experiments, we reveal that cathepsin B is
      involved in both the induction of cell death and inflammasome activation upon
      infection with wild-type mycobacteria. These results reveal distinct roles for
      two different type VII secretion systems during infection and shed light on how
      virulent mycobacteria manipulate the host cell in various ways to replicate and
      spread.

PMID- 21957140
TI  - Contributions of direct and indirect alloresponses to chronic rejection of kidney
      allografts in nonhuman primates.
AB  - The relative contribution of direct and indirect allorecognition pathways to
      chronic rejection of allogeneic organ transplants in primates remains unclear. In
      this study, we evaluated T and B cell alloresponses in cynomolgus monkeys that
      had received combined kidney/bone marrow allografts and myeloablative
      immunosuppressive treatments. We measured donor-specific direct and indirect T
      cell responses and alloantibody production in monkeys (n = 5) that did not reject
      their transplant acutely but developed chronic humoral rejection (CHR) and in
      tolerant recipients (n = 4) that never displayed signs of CHR. All CHR recipients
      exhibited high levels of anti-donor Abs and mounted potent direct T cell
      alloresponses in vitro. Such direct alloreactivity could be detected for more
      than 1 y after transplantation. In contrast, only two of five monkeys with CHR
      had a detectable indirect alloresponse. No indirect alloresponse by T cells and
      no alloantibody responses were found in any of the tolerant monkeys. Only one of
      four tolerant monkeys displayed a direct T cell alloresponse. These observations
      indicate that direct T cell alloresponses can be sustained for prolonged periods
      posttransplantation and result in alloantibody production and chronic rejection
      of kidney transplants, even in the absence of detectable indirect alloreactivity.

PMID- 21957141
TI  - Hydrogen sulfide upregulates cyclooxygenase-2 and prostaglandin E metabolite in
      sepsis-evoked acute lung injury via transient receptor potential vanilloid type 1
      channel activation.
AB  - Hydrogen sulfide (H(2)S) has been shown to promote transient receptor potential
      vanilloid type 1 (TRPV1)-mediated neurogenic inflammation in sepsis and its
      associated multiple organ failure, including acute lung injury (ALI).
      Accumulating evidence suggests that the cyclooxygenase-2 (COX-2)/PGE(2) pathway
      plays an important role in augmenting inflammatory immune response in sepsis and
      respiratory diseases. However, the interactions among H(2)S, COX-2, and PGE(2) in
      inciting sepsis-evoked ALI remain unknown. Therefore, the aim of this study was
      to investigate whether H(2)S would upregulate COX-2 and work in conjunction with
      it to instigate ALI in a murine model of polymicrobial sepsis. Polymicrobial
      sepsis was induced by cecal ligation and puncture (CLP) in male Swiss mice. dl
      propargylglycine, an inhibitor of H(2)S formation, was administrated 1 h before
      or 1 h after CLP, whereas sodium hydrosulfide, an H(2)S donor, was given during
      CLP. Mice were treated with TRPV1 antagonist capsazepine 30 min before CLP,
      followed by assessment of lung COX-2 and PGE(2) metabolite (PGEM) levels.
      Additionally, septic mice were administrated with parecoxib, a selective COX-2
      inhibitor, 20 min post-CLP and subjected to ALI and survival analysis. H(2)S
      augmented COX-2 and PGEM production in sepsis-evoked ALI by a TRPV1 channel
      dependent mechanism. COX-2 inhibition with parecoxib attenuated H(2)S-augmented
      lung PGEM production, neutrophil infiltration, edema, proinflammatory cytokines,
      chemokines, and adhesion molecules levels, restored lung histoarchitecture, and
      protected against CLP-induced lethality. The strong anti-inflammatory and
      antiseptic actions of selective COX-2 inhibitor may provide a potential
      therapeutic approach for the management of sepsis and sepsis-associated ALI.

PMID- 21957142
TI  - Hepatitis B virus induces a novel inflammation network involving three
      inflammatory factors, IL-29, IL-8, and cyclooxygenase-2.
AB  - Chronic inflammation induced by hepatitis B virus (HBV) is a major causative
      factor associated with the development of cirrhosis and hepatocellular carcinoma.
      In this study, we investigated the roles of three inflammatory factors, IL-8, IL
      29 (or IFN-lambda1), and cyclooxygenase-2 (COX-2), in HBV infection. We showed
      that the expression of IL-29, IL-8, and COX-2 genes was enhanced in HBV-infected
      patients or in HBV-expressing cells. In HBV-transfected human lymphocytes and
      hepatocytes, IL-29 activates the production of IL-8, which in turn enhances the
      expression of COX-2. In addition, COX-2 decreases the production of IL-8, which
      in turn attenuates the expression of IL-29. Thus, we proposed that HBV infection
      induces a novel inflammation cytokine network involving three inflammatory
      factors that regulate each other in the order IL-29/IL-8/COX-2, which involves
      positive regulation and negative feedback. In addition, we also demonstrated that
      COX-2 expression activated by IL-8 was mediated through CREB and C/EBP, which
      maintains the inflammatory environment associated with HBV infection. Finally, we
      showed that the ERK and the JNK signaling pathways were cooperatively involved in
      the regulation of COX-2. We also demonstrated that IL-29 inhibits HBV replication
      and that IL-8 attenuates the expression of IL-10R2 and the anti-HBV activity of
      IL-29, which favors the establishment of persistent viral infection. These new
      findings provide insights for our understanding of the mechanism by which
      inflammatory factors regulate each other in response to HBV infection.

PMID- 21957143
TI  - Critical roles of ASC inflammasomes in caspase-1 activation and host innate
      resistance to Streptococcus pneumoniae infection.
AB  - Streptococcus pneumoniae is a Gram-positive, extracellular bacterium that is
      responsible for significant mortality and morbidity worldwide. Pneumolysin (PLY),
      a cytolysin produced by all clinical isolates of the pneumococcus, is one of the
      most important virulence factors of this pathogen. We have previously reported
      that PLY is an essential factor for activation of caspase-1 and consequent
      secretion of IL-1beta and IL-18 in macrophages infected with S. pneumoniae.
      However, the host molecular factors involved in caspase-1 activation are still
      unclear. To further elucidate the mechanism of caspase-1 activation in
      macrophages infected with S. pneumoniae, we examined the involvement of
      inflammasomes in inducing this cellular response. Our study revealed that
      apoptosis-associated specklike protein containing a caspase recruitment domain
      (ASC), an adaptor protein for inflammasome receptors such as nucleotide-binding
      oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3)
      and absent in melanoma 2 (AIM2), is essentially required for the induction of
      caspase-1 activation by S. pneumoniae. Caspase-1 activation was partially
      impaired in NLRP3(-/-) macrophages, whereas knockdown and knockout of AIM2
      resulted in a clear decrease in caspase-1 activation in response to S.
      pneumoniae. These results suggest that ASC inflammasomes, including AIM2 and
      NLRP3, are critical for caspase-1 activation induced by S. pneumoniae.
      Furthermore, ASC(-/-) mice were more susceptible than wild-type mice to S.
      pneumoniae, with impaired secretion of IL-1beta and IL-18 into the
      bronchoalveolar lavage after intranasal infection, suggesting that ASC
      inflammasomes contribute to the protection of host from infection with PLY
      producing S. pneumoniae.

PMID- 21957144
TI  - Critical roles of RasGRP1 for invariant NKT cell development.
AB  - The invariant NKT (iNKT) cell lineage contains CD4(+) and CD4(-) subsets. The
      mechanisms that control such subset differentiation and iNKT cell maturation in
      general have not been fully understood. RasGRP1, a guanine nucleotide exchange
      factor for TCR-induced activation of the Ras-ERK1/2 pathway, is critical for
      conventional alphabeta T cell development but dispensable for generating
      regulatory T cells. Its role in iNKT cells has been unknown. In this study, we
      report severe decreases of iNKT cells in RasGRP1(-/-) mice through cell intrinsic
      mechanisms. In the remaining iNKT cells in RasGRP1(-/-) mice, there is a
      selective absence of the CD4(+) subset. Furthermore, RasGRP1(-/-) iNKT cells are
      defective in TCR-induced proliferation in vitro. These observations establish
      that RasGRP1 is not only important for early iNKT cell development but also for
      the generation/maintenance of the CD4(+) iNKT cells. Our data provide genetic
      evidence that the CD4(+) and CD4(-) iNKT cells are distinct sublineages with
      differential signaling requirements for their development.

PMID- 21957145
TI  - Mechanism for pre-B cell loss in VH-mutant rabbits.
AB  - Pre-BCR signaling is a critical checkpoint in B cell development in which B
      lineage cells expressing functional IgH MU-chain are selectively expanded. B cell
      development is delayed in mutant ali/ali rabbits because the a-allotype encoding
      V(H)1 gene, which is normally used in VDJ gene rearrangements in wt rabbits, is
      deleted, and instead, most B-lineage cells use the a-allotype encoding V(H)4 gene
      [V(H)4(a)], which results in a severe developmental block at the pre-B cell
      stage. We found that V(H)4(a)-utilizing pre-B cells exhibit reduced pre-BCR
      signaling and do not undergo normal expansion in vitro. Transduction of murine
      38B9 pre-B cells with chimeric rabbit-VDJ mouse-CMU encoding retroviruses showed
      V(H)4(a)-encoded MU-chains do not readily form signal-competent pre-BCR, thereby
      explaining the reduction in pre-BCR signaling and pre-B cell expansion.
      Development of V(H)4(a)-utilizing B cells can be rescued in vivo by the
      expression of an Igkappa transgene, indicating that V(H)4(a)-MU chains are not
      defective for conventional BCR formation and signaling. The ali/ali rabbit model
      system is unique because V(H)4(a)-MU chains have the capacity to pair with a
      variety of conventional IgL chains and yet lack the capacity to form a signal
      competent pre-BCR. This system could allow for identification of critical
      structural parameters that govern pre-BCR formation/signaling.

PMID- 21957146
TI  - Prmt2 regulates the lipopolysaccharide-induced responses in lungs and
      macrophages.
AB  - Precise control of the LPS stimulation in the lung modulates inflammation and
      airway hyperresponsiveness involving the well-known TLR4/NF-kappaB pathway. As a
      consequence, the expression and secretion of proinflammatory cytokines is tightly
      regulated with the recruitment of neutrophils. Changes in the LPS-induced
      responses have been observed in the Prmt2-Col6a1 monosomic model, suggesting the
      presence of dosage-sensitive genes controlling LPS pathway in the mouse. In this
      article, we report that the Prmt2 regulates the LPS-induced lung responses in
      lungs and macrophages. We demonstrate that Prmt2 gene dosage influences the lung
      airway hyperresponsiveness, the recruitment of neutrophils, and the expression of
      proinflammatory cytokines, such as IL-6 and TNF-alpha. In addition, Prmt2 loss of
      function also altered the nuclear accumulation of NF-kappaB in stimulated
      macrophages. Prmt2 should be considered as a new member of the NF-kappaB pathway
      controlling LPS-induced inflammatory and lung responses in a dosage-dependent
      manner, certainly through regulating nuclear accumulation of NF-kappaB as shown
      already in fibroblasts.

PMID- 21957147
TI  - HIV-1 N-glycan composition governs a balance between dendritic cell-mediated
      viral transmission and antigen presentation.
AB  - The natural function of dendritic cells (DCs) is to capture and degrade pathogens
      for Ag presentation. However, HIV-1 can evade viral degradation by DCs and hijack
      DCs for migration to susceptible CD4(+) T lymphocytes. It is unknown what factors
      decide whether a virus is degraded or transmitted to T cells. The interaction of
      DCs with HIV-1 involves C-type lectin receptors, such as DC-specific ICAM-3
      grabbing nonintegrin, which bind to the envelope glycoprotein complex (Env),
      which is decorated heavily with N-linked glycans. We hypothesized that the
      saccharide composition of the Env N-glycans is involved in avoiding viral
      degradation and Ag presentation, as well as preserving infectious virus for the
      transmission to target cells. Therefore, we studied the fate of normally
      glycosylated virus versus oligomannose-enriched virus in DCs. Changing the
      heterogeneous N-linked glycan composition of Env to uniform oligomannose N
      glycans increased the affinity of HIV-1 for DC-specific ICAM-3-grabbing
      nonintegrin and enhanced the capture of HIV-1 by immature DCs; however, it
      decreased the subsequent transmission to target cells. Oligomannose-enriched HIV
      1 was directed more efficiently into the endocytic pathway, resulting in enhanced
      viral degradation and reduced virus transfer to target cells. Furthermore, Env
      containing exclusively oligomannose N-glycans was presented to Env-specific
      CD4(+) T cells more efficiently. Taken together, our results showed that the HIV
      1 N-glycan composition plays a crucial role in the balance between DC-mediated Ag
      degradation and presentation and DC-mediated virus transmission to target cells.
      This finding may have implications for the early events in HIV-1 transmission and
      the induction of antiviral immune responses.

PMID- 21957148
TI  - Intracellular HMGB1 negatively regulates efferocytosis.
AB  - High mobility group box 1 (HMGB1) is a highly conserved protein with multiple
      intracellular and extracellular functions, including transcriptional regulation,
      as well as modulation of inflammation, cell migration, and ingestion of apoptotic
      cells. In these experiments, we examined a potential role for intracellular HMGB1
      in modulating phagocytosis. We found that phagocytosis of apoptotic cells
      resulted in translocation of HMGB1 into the cytoplasm and extracellular space.
      Transient or stable inhibition of HMGB1 expression in bone marrow-derived
      macrophages or fibroblasts resulted in increased phagocytosis of apoptotic
      thymocytes and apoptotic neutrophils. Knockdown of HMGB1 was associated with
      enhanced activation of Rac-1 and cytoskeletal rearrangement. Intracellular events
      involved in phagocytosis and upstream of Rac-1 activation, such as
      phosphorylation of ERK and focal adhesion kinase (FAK), were increased after
      knockdown of HMGB1. Inhibition of Src kinase activity prevented the increase in
      phosphorylation of FAK and ERK present during phagocytosis in HMGB1 knockdown
      cells, and also abrogated the enhancement in phagocytosis associated with HMGB1
      knockdown. Interaction between Src and FAK in the cytoplasm of HMGB1 knockdown
      fibroblasts was enhanced compared with that present in control fibroblasts. Under
      in vitro conditions, the presence of HMGB1 diminished interactions between
      purified FAK and Src. These studies demonstrate a novel role for HMGB1 in the
      regulation of phagocytosis. In particular, these experiments show that
      intracellular HMGB1, through associating with Src kinase and inhibiting
      interactions between Src and FAK, diminishes the phagocytic ability of
      macrophages and other cell populations.

PMID- 21957149
TI  - DHX9 pairs with IPS-1 to sense double-stranded RNA in myeloid dendritic cells.
AB  - The innate immune system is equipped with many molecular sensors for microbial
      DNA/RNA to quickly mount antimicrobial host immune responses. In this paper, we
      identified DHX9, a DExDc helicase family member, as an important viral dsRNA
      sensor in myeloid dendritic cells (mDCs). Knockdown of DHX9 expression by small
      heteroduplex RNA dramatically blocked the ability of mDCs to produce IFN
      alpha/beta and proinflammatory cytokines in response to polyinosine-polycytidylic
      acid, influenza A, and reovirus. DHX9 could specifically bind polyinosine
      polycytidylic acid via its double-strand RNA binding motifs. DHX9 interacted with
      IPS-1 via the HelicC-HA2-DUF and CARD domains of DHX9 and IPS-1, respectively.
      Knockdown of DHX9 expression in mDCs blocked the activation of NF-kappaB and IFN
      regulatory factor 3 by dsRNA. Collectively, these results suggest that DHX9 is an
      important RNA sensor that is dependent on IPS-1 to sense pathogenic RNA.

PMID- 21957150
TI  - Pyridone 6, a pan-JAK inhibitor, ameliorates allergic skin inflammation of NC/Nga
      mice via suppression of Th2 and enhancement of Th17.
AB  - Atopic dermatitis (AD) is a common pruritic inflammatory disease triggered by a
      defective skin barrier and immunodysregulation. AD has been considered a typical
      example of a Th2 response associated with allergic disease. In the early phases
      of the disease, symptoms include IgE hyperproduction, eosinophil accumulation,
      and mast cell activation; in the chronic phase, a Th1-dominant immune response is
      also observed at the sites of AD skin lesions. The role of IL-17-producing Th
      (Th17) cells in AD has not been established. In the current study, we found that
      pyridone 6 (P6), a pan-JAK inhibitor, delayed the onset and reduced the magnitude
      of skin disease in an AD-like skin-disease model of NC/Nga mice. P6 reduced IFN
      gamma and IL-13, whereas it enhanced IL-17 and IL-22 expression. In vitro, P6
      also inhibited both Th1 and Th2 development, whereas it promoted Th17
      differentiation from naive T cells when present within a certain range of
      concentrations. This was probably because P6 strongly inhibited STAT1, STAT5, and
      STAT6 phosphorylation, whereas STAT3 phosphorylation was less efficiently
      suppressed by P6 at the same concentration. Furthermore, IL-22 protects
      keratinocytes from apoptosis induced by IFN-gamma, and administration of IL-17
      and IL-22 partially ameliorated skin diseases in NC/Nga mice. These results
      suggested that the JAK inhibitor P6 is therapeutic for AD by modulating the
      balance of Th2 and Th17.

PMID- 21957151
TI  - IL-13 receptor alpha1 differentially regulates aeroallergen-induced lung
      responses.
AB  - IL-13 and IL-4 are hallmark cytokines of Th2-associated diseases including
      asthma. Recent studies revealed that IL-13Ralpha1 regulates asthma pathogenesis
      by mediating both IL-4- and IL-13-mediated responses. Nonetheless, the relative
      contribution of each cytokine in response to aeroallergen challenge and the
      degree of functional dichotomy between IL-4 and IL-13 in asthma remains unclear.
      Consistent with prior publications, we demonstrate that IL-13Ralpha1 regulates
      aeroallergen-induced airway resistance and mucus production but not IgE and Th2
      cytokine production. We demonstrate that aeroallergen-induced eosinophil
      recruitment and chemokine production were largely dependent on IL-13Ralpha1 after
      Aspergillus but not house dust mite (HDM) challenges. Notably, Aspergillus
      challenged mice displayed increased IL-13Ralpha1-dependent accumulation of
      dendritic cell subsets into lung-draining lymph nodes in comparison with HDM
      challenged mice. Comparison of IL-4 and IL-13 levels in the different
      experimental models revealed increased IL-4/IL-13 ratios after HDM challenge,
      likely explaining the IL-13Ralpha1-independent eosinophilia and chemokine
      production. Consistently, eosinophil adoptive transfer experiments revealed near
      ablation of lung eosinophilia in response to Aspergillus in Il13ra1(-/-) mice,
      suggesting that Aspergillus-induced lung eosinophil recruitment is regulated by
      IL-13-induced chemokine production rather than altered IL-13 signaling in
      eosinophils. Furthermore, the near complete protection observed in Il13ra1(-/-)
      mice in response to Aspergillus challenge was dependent on mucosal sensitization,
      as alum/Aspergillus-sensitized mice that were rechallenged with Aspergillus
      developed IL-13Ralpha1-independent eosinophilia although other asthma parameters
      remained IL-13Ralpha1 dependent. These results establish that IL-13Ralpha1 is
      required for aeroallergen-induced airway resistance and that allergen-induced
      chemokine production and consequent eosinophilia is dictated by the balance
      between IL-4 and IL-13 production in situ.

PMID- 21957153
TI  - Comparative immunogenicity and cross-clade protective efficacy of mammalian cell
      grown inactivated and live attenuated H5N1 reassortant vaccines in ferrets.
AB  - Continued H5N1 virus infection in humans highlights the need for vaccine
      strategies that provide cross-clade protection against this rapidly evolving
      virus. We report a comparative evaluation in ferrets of the immunogenicity and
      cross-protective efficacy of isogenic mammalian cell-grown, live attenuated
      influenza vaccine (LAIV) and adjuvanted, whole-virus, inactivated influenza
      vaccine (IIV), produced from a clade 1 H5N1 6:2 reassortant vaccine candidate
      (caVN1203-Len17rg) based on the cold-adapted A/Leningrad/134/17/57 (H2N2) master
      donor virus. Two doses of LAIV or IIV provided complete protection against lethal
      homologous H5N1 virus challenge and a reduction in virus shedding and disease
      severity after heterologous clade 2.2.1 H5N1 virus challenge and increased virus
      specific serum and nasal wash antibody levels. Although both vaccines
      demonstrated cross-protective efficacy, LAIV induced higher levels of nasal wash
      IgA and reduction of heterologous virus shedding, compared with IIV. Thus,
      enhanced respiratory tract antibody responses elicited by LAIV were associated
      with improved cross-clade protection.

PMID- 21957152
TI  - Late-replicating heterochromatin is characterized by decreased cytosine
      methylation in the human genome.
AB  - Heterochromatin is believed to be associated with increased levels of cytosine
      methylation. With the recent availability of genome-wide, high-resolution
      molecular data reflecting chromatin organization and methylation, such
      relationships can be explored systematically. As well-defined surrogates for
      heterochromatin, we tested the relationship between DNA replication timing and
      DNase hypersensitivity with cytosine methylation in two human cell types,
      unexpectedly finding the later-replicating, more heterochromatic regions to be
      less methylated than early replicating regions. When we integrated gene
      expression data into the study, we found that regions of increased gene
      expression were earlier replicating, as previously identified, and that
      transcription-targeted cytosine methylation in gene bodies contributes to the
      positive correlation with early replication. A self-organizing map (SOM) approach
      was able to identify genomic regions with early replication and increased
      methylation, but lacking annotated transcripts, loci missed in simple two
      variable analyses, possibly encoding unrecognized intergenic transcripts. We
      conclude that the relationship of cytosine methylation with heterochromatin is
      not simple and depends on whether the genomic context is tandemly repetitive
      sequences often found near centromeres, which are known to be heterochromatic and
      methylated, or the remaining majority of the genome, where cytosine methylation
      is targeted preferentially to the transcriptionally active, euchromatic
      compartment of the genome.

PMID- 21957155
TI  - Increased risk of acute pancreatitis among tetracycline users in a Swedish
      population-based case-control study.
AB  - OBJECTIVE: To evaluate the suggested association between tetracycline and acute
      pancreatitis in a large pharmacoepidemiological study. DESIGN: The use of
      tetracycline in relation to the risk of acute pancreatitis was examined in a
      nationwide case-control study of people aged 40-84 years between 2006 and 2008 in
      Sweden. The Swedish Patient Register was used to identify 6161 cases of first
      episode acute pancreatitis. The Register of the Total Population was used to
      randomly select 61,637 control subjects from the general population using
      frequency-based density sampling, matched for age, sex, and calendar year.
      Tetracycline use was defined as 'current', 'recent', 'past' or 'former' if the
      drug had been dispensed 0-30 days, 31-180 days, 181-365 days or 1-31/2 years
      before the index date, respectively. The risk of acute pancreatitis was estimated
      by unconditional logistic regression, providing ORs with 95% CIs, adjusted for
      potential confounding factors. RESULTS: There was a 60% increased risk of acute
      pancreatitis among current users of tetracycline after adjustment for potential
      confounders (OR=1.6, 95% CI 1.2 to 2.1). There was no increased OR for any
      category of previous use. CONCLUSION: Current use of tetracycline is associated
      with an increased risk of acute pancreatitis, verifying previous case reports.

PMID- 21957154
TI  - Synthesis and distribution of CARDS toxin during Mycoplasma pneumoniae infection
      in a murine model.
AB  - Mice were infected with Mycoplasma pneumoniae and monitored for the synthesis and
      distribution of the unique adenosine diphosphate-ribosylating and vacuolating
      Community Acquired Respiratory Distress Syndrome (CARDS) toxin in bronchiolar
      lavage fluid (BALF) and lung. We noted direct relationships between the
      concentration of CARDS toxin and numbers of mycoplasma genomes in BALF and the
      degree of histologic pulmonary inflammation. Immunostaining of lungs revealed
      extensive colonization by mycoplasmas, including the detection of CARDS toxin in
      the corresponding inflamed airways. Lung lesion scores were higher during the
      early stages of infection, decreased gradually by day 14 postinfection, and
      reached substantially lower values at day 35. Infected mouse immunoglobulin (Ig)
      M and IgG titers were positive for CARDS toxin as well as for the major adhesin
      P1 of M. pneumoniae. These data reinforce the proposed pathogenic role of CARDS
      toxin in M. pneumoniae-mediated pathologies.

PMID- 21957156
TI  - Baroreflex control of muscle sympathetic nerve activity as a mechanism for
      persistent sympathoexcitation following acute hypoxia in humans.
AB  - This study tested the hypothesis that acute isocapnic hypoxia results in
      persistent resetting of the baroreflex to higher levels of muscle sympathetic
      nerve activity (MSNA), which outlasts the hypoxic stimulus. Cardiorespiratory
      measures were recorded in humans (26 +/- 1 yr; n = 14; 3 women) during baseline,
      exposure to 20 min of isocapnic hypoxia, and for 5 min following termination of
      hypoxia. The spontaneous baroreflex threshold technique was used to determine the
      change in baroreflex function during and following 20 min of isocapnic hypoxia
      (oxyhemoglobin saturation = 80%). From the spontaneous baroreflex analysis, the
      linear regression between diastolic blood pressure (DBP) and sympathetic burst
      occurrence, the T50 (DBP with a 50% likelihood of a burst occurring), and DBP
      error signal (DBP minus the T50) provide indexes of baroreflex function. MSNA and
      DBP increased in hypoxia and remained elevated during posthypoxia relative to
      baseline (P < 0.05). The DBP error signal became progressively less negative
      (i.e., smaller difference between DBP and T50) in the hypoxia and posthypoxia
      periods (baseline: -3.9 +/- 0.8 mmHg; hypoxia: -1.4 +/- 0.6 mmHg; posthypoxia:
      0.2 +/- 0.6 mmHg; P < 0.05). Hypoxia caused no change in the slope of the
      baroreflex stimulus-response curve; however, there was a shift toward higher
      pressures that favored elevations in MSNA, which persisted posthypoxia. Our
      results indicate that there is a resetting of the baroreflex in hypoxia that
      outlasts the stimulus and provide further explanation for the complex control of
      MSNA following acute hypoxia.

PMID- 21957157
TI  - Impact of a single session of intermittent pneumatic leg compressions on skeletal
      muscle and isolated artery gene expression in rats.
AB  - Intermittent pneumatic leg compressions (IPC) have proven to be an effective
      noninvasive approach for treatment of patients with claudication, but the
      mechanisms underlying the clinical benefits remain elusive. In the present study,
      a rodent model of claudication produced by bilateral ligation of the femoral
      artery was used to investigate the acute impact of a single session of IPC (150
      min) on hemodynamics, skeletal muscle (tibialis anterior), and isolated
      collateral artery (perforating artery) expression of a subset of genes associated
      with inflammation and vascular remodeling. In addition, the effect of compression
      frequency (15 vs. 3 compressions/min) on the expression of these factors was
      studied. In ligated animals, IPC evoked an increase of monocyte chemoattractant
      protein-1 (MCP-1) and cytokine-induced neutrophil chemoattractant 1 (CXCL1) mRNA
      (P < 0.01) and immunostaining (P < 0.05), as well as a minor increase in VEGF
      immunostaining in the muscle endomysium 150 min postintervention. Further,
      collateral arteries from these animals showed an increased expression of MCP-1
      (approximately twofold, P = 0.02). These effects were most evident in the group
      exposed to the high-frequency protocol (15 compressions/min). In contrast, IPC in
      sham-operated control animals evoked a modest initial upregulation of VEGF (P =
      0.01), MCP-1 (P = 0.02), and CXCL1 (P = 0.03) mRNA in the muscle without
      concomitant changes in protein levels. No changes in gene expression were
      observed in arteries isolated from sham animals. In conclusion, IPC acutely up
      regulates the expression of important factors involved in vascular remodeling in
      the compressed muscle and collateral arteries in a model of hindlimb ischemia.
      These effects appear to be dependent on the compression frequency, such that a
      high compression frequency (15 compressions/min) evokes more consistent and
      robust effects compared with the frequency commonly employed clinically to treat
      patients with claudication (3 compressions/min).

PMID- 21957158
TI  - Heat acclimation and exercise training interact when combined in an overriding
      and trade-off manner: physiologic-genomic linkage.
AB  - Combined heat acclimation (AC) and exercise training (EX) enhance exercise
      performance in the heat while meeting thermoregulatory demands. We tested the
      hypothesis that different stress-specific adaptations evoked by each stressor
      individually trigger similar cardiac alterations, but when combined,
      overriding/trade-off interactions take place. We used echocardiography, isolated
      cardiomyocyte imaging and cDNA microarray techniques to assay in situ cardiac
      performance, excitation-contraction (EC) coupling features, and transcriptional
      programs associated with cardiac contractility. Rat groups studied were controls
      (sedentary 24 degrees C); AC (sedentary, 34 degrees C, 1 mo); normothermic EX
      (treadmill at 24 degrees C, 1 mo); and heat-acclimated, exercise-trained (EXAC;
      treadmill at 34 degrees C, 1 mo). Prolonged heat exposure decreased heart rate
      and contractile velocity and increased end ventricular diastolic diameter.
      Compared with controls, AC/EXAC cardiomyocytes demonstrated lower l-type Ca(2+)
      current (I(CaL)) amplitude, higher Ca(2+) transient (Ca(2+)T), and a greater
      Ca(2+)T-to-I(CaL) ratio; EX alone enhanced I(CaL) and Ca(2+)T, whereas aerobic
      training in general induced cardiac hypertrophy and action potential elongation
      in EX/EXAC animals. At the genomic level, the transcriptome profile indicated
      that the interaction between AC and EX yields an EXAC-specific molecular program.
      Genes affected by chronic heat were linked with the EC coupling cascade, whereas
      aerobic training upregulated genes involved with Ca(2+) turnover via an
      adrenergic/metabolic-driven positive inotropic response. In the EXAC cardiac
      phenotype, the impact of chronic heat overrides that of EX on EC coupling
      components and heart rate, whereas EX regulates cardiac morphometry. We suggest
      that concerted adjustments induced by AC and EX lead to enhanced metabolic and
      mechanical performance of the EXAC heart.

PMID- 21957159
TI  - Stimulation of the hypothalamic ventromedial nuclei by pituitary adenylate
      cyclase-activating polypeptide induces hypophagia and thermogenesis.
AB  - Numerous studies have demonstrated that the hypothalamic ventromedial nuclei
      (VMN) regulate energy homeostasis by integrating and utilizing behavioral and
      metabolic mechanisms. The VMN heavily express pituitary adenylate cyclase
      activating polypeptide (PACAP) type I receptors (PAC1R). Despite the receptor
      distribution, most PACAP experiments investigating affects on feeding have
      focused on intracerebroventricular administration or global knockout mice. To
      identify the specific contribution of PACAP signaling in the VMN, we injected
      PACAP directly into the VMN and measured feeding behavior and indices of energy
      expenditure. Following an acute injection of PACAP, nocturnal food intake was
      significantly reduced for 6 h after injections without evidence of malaise. In
      addition, PACAP-induced suppression of feeding also occurred following an
      overnight fast and could be blocked by a specific PAC1R antagonist.
      Metabolically, VMN-specific injections of PACAP significantly increased both core
      body temperature and spontaneous locomotor activity with a concurrent increase in
      brown adipose uncoupling protein 1 mRNA expression. To determine which signaling
      pathways were responsive to PACAP administration into the VMN, we measured mRNA
      expression of well-characterized hypothalamic neuropeptide regulators of feeding.
      One hour after PACAP administration, expression of pro-opiomelanocortin mRNA was
      significantly increased in the arcuate nuclei (ARC), with no changes in
      neuropeptide Y and agouti-related polypeptide mRNA levels. This suggests that
      PAC1R expressing VMN neurons projecting to pro-opiomelanocortin neurons
      contribute to hypophagia by involving melanocortin signaling. While the VMN also
      abundantly express PACAP protein, the present study demonstrates that PACAP input
      to the VMN can influence the control of energy homeostasis.

PMID- 21957160
TI  - Experimental evidence for therapeutic potential of taurine in the treatment of
      nonalcoholic fatty liver disease.
AB  - The incidence of obesity is now at epidemic proportions and has resulted in the
      emergence of nonalcoholic fatty liver disease (NAFLD) as a common metabolic
      disorder that can lead to liver injury and cirrhosis. Excess sucrose and long
      chain saturated fatty acids in the diet may play a role in the development and
      progression of NAFLD. One factor linking sucrose and saturated fatty acids to
      liver damage is dysfunction of the endoplasmic reticulum (ER). Although there is
      currently no proven, effective therapy for NAFLD, the amino sulfonic acid taurine
      is protective against various metabolic disturbances, including alcohol-induced
      liver damage. The present study was undertaken to evaluate the therapeutic
      potential of taurine to serve as a preventative treatment for diet-induced NAFLD.
      We report that taurine significantly mitigated palmitate-mediated caspase-3
      activity, cell death, ER stress, and oxidative stress in H4IIE liver cells and
      primary hepatocytes. In rats fed a high-sucrose diet, dietary taurine
      supplementation significantly reduced hepatic lipid accumulation, liver injury,
      inflammation, plasma triglycerides, and insulin levels. The high-sucrose diet
      resulted in an induction of multiple components of the unfolded protein response
      in the liver consistent with ER stress, which was ameliorated by taurine
      supplementation. Treatment of mice with the ER stress-inducing agent tunicamycin
      resulted in liver injury, unfolded protein response induction, and hepatic lipid
      accumulation that was significantly ameliorated by dietary supplementation with
      taurine. Our results indicate that dietary supplementation with taurine offers
      significant potential as a preventative treatment for NAFLD.

PMID- 21957161
TI  - Social technology restriction alters state-anxiety but not autonomic activity in
      humans.
AB  - Social technology is extensively used by young adults throughout the world, and
      it has been suggested that interrupting access to this technology induces
      anxiety. However, the influence of social technology restriction on anxiety and
      autonomic activity in young adults has not been formally examined. Therefore, we
      hypothesized that restriction of social technology would increase state-anxiety
      and alter neural cardiovascular regulation of arterial blood pressure. Twenty-one
      college students (age 18-23 yr) were examined during two consecutive weeks in
      which social technology use was normal or restricted (randomized crossover
      design). Mean arterial pressure (MAP), heart rate, and muscle sympathetic nerve
      activity (MSNA) were measured at rest and during several classic autonomic
      stressors, including isometric handgrip, postexercise muscle ischemia, cold
      pressor test, and mental stress. Tertile analysis revealed that restriction of
      social technology was associated with increases (12 +/- 2 au; range 5 to 21; n =
      7), decreases (-6 +/- 2 au; range -2 to -11; n = 6), or no change (0 +/- 0 au;
      range -1 to 3; n = 8) in state-anxiety. Social technology restriction did not
      alter MAP (74 +/- 1 vs. 73 +/- 1 mmHg), heart rate (62 +/- 2 vs. 61 +/- 2
      beats/min), or MSNA (9 +/- 1 vs. 9 +/- 1 bursts/min) at rest, and it did not
      alter neural or cardiovascular responses to acute stressors. In conclusion,
      social technology restriction appears to have an interindividual influence on
      anxiety, but not autonomic activity. It remains unclear how repeated bouts, or
      chronic restriction of social technology, influence long-term psychological and
      cardiovascular health.

PMID- 21957162
TI  - Rate of fall in blood glucose and recurrent hypoglycemia affect glucose dynamics
      and noradrenergic activation in the ventromedial hypothalamus.
AB  - Noradrenergic activity in the ventromedial hypothalamus (VMH) is increased and
      activates a sympathoadrenal response during hypoglycemia. How the rate at which
      hypoglycemia develops affects local glucose concentrations and norepinephrine
      (NE) release was evaluated by placing microdialysis probes into the VMH of male
      Sprague-Dawley rats receiving insulin (20 mU.kg(-1).min(-1)) and variable glucose
      infusions. During a first episode of hypoglycemia, interstitial glucose
      concentrations in the VMH generally declined at the same rate as plasma glucose;
      however, the faster hypoglycemia developed, the greater the magnitude of the
      initial NE release in the VMH (r(2) = 0.72, P < 0.001). Following recurrent
      episodes of hypoglycemia, VMH glucose decreased at a slower rate than plasma
      glucose, and the initial NE release was attenuated at the same rates of blood
      glucose decline. The plasma glucose threshold for the initial NE release in VMH
      was similar for all groups (~3.23 mM); however, the VMH glucose threshold was
      stimulated and was lower when blood glucose declined more slowly (0.86 +/- 0.06
      vs. 1.06 +/- 0.04 mmol/l, P < 0.01). The timing of the initial increase in NE
      release in VMH corresponded with an increase in plasma epinephrine during the
      first episode of hypoglycemia but not following recurrent hypoglycemia. Although
      a decrease in VMH glucose concentration is required for noradrenergic activation
      in VMH, there does not appear to be a set glucose threshold within the VMH for
      activation of this response.

PMID- 21957163
TI  - Altered sleep and behavioral activity phenotypes in PER3-deficient mice.
AB  - Sleep homeostasis and circadian rhythmicity interact to determine the timing of
      behavioral activity. Circadian clock genes contribute to circadian rhythmicity
      centrally and in the periphery, but some also have roles within sleep regulation.
      The clock gene Period3 (Per3) has a redundant function within the circadian
      system and is associated with sleep homeostasis in humans. This study
      investigated the role of PER3 in sleep/wake activity and sleep homeostasis in
      mice by recording wheel-running activity under baseline conditions in wild-type
      (WT; n = 54) and in PER3-deficient (Per3(-/-); n = 53) mice, as well as EEG
      assessed sleep before and after 6 h of sleep deprivation in WT (n = 7) and Per3(
      /-) (n = 8) mice. Whereas total activity and vigilance states did not differ
      between the genotypes, the temporal distribution of wheel-running activity,
      vigilance states, and EEG delta activity was affected by genotype. In Per3(-/-)
      mice, running wheel activity was increased, and REM sleep and NREM sleep were
      reduced in the middle of the dark phase, and delta activity was enhanced at the
      end of the dark phase. At the beginning of the baseline light period, there was
      less wakefulness and more REM and NREM sleep in Per3(-/-) mice. Per3(-/-) mice
      spent less time in wakefulness and more time in NREM sleep in the light period
      immediately after sleep deprivation, and REM sleep accumulated more slowly during
      the recovery dark phase. These data confirm a role for PER3 in sleep-wake timing
      and sleep homeostasis.

PMID- 21957164
TI  - Effect of initial core temperature on hyperthermic hyperventilation during
      prolonged submaximal exercise in the heat.
AB  - We investigated whether a core temperature threshold for hyperthermic
      hyperventilation is seen during prolonged submaximal exercise in the heat when
      core temperature before the exercise is reduced and whether the evoked
      hyperventilatory response is affected by altering the initial core temperature.
      Ten male subjects performed three exercise trials at 50% of peak oxygen uptake in
      the heat (37 degrees C and 50% relative humidity) after altering their initial
      esophageal temperature (T(es)). Initial T(es) was manipulated by immersion for 25
      min in water at 18 degrees C (Precooling), 35 degrees C (Control), or 40 degrees
      C (Preheating). T(es) after the water immersion was significantly higher in the
      Preheating trial (37.5 +/- 0.3 degrees C) and lower in the Precooling trial (36.1
      +/- 0.3 degrees C) than in the Control trial (36.9 +/- 0.3 degrees C). In the
      Precooling trial, minute ventilation (Ve) showed little change until T(es)
      reached 37.1 +/- 0.4 degrees C. Above this core temperature threshold, Ve
      increased linearly in proportion to increasing T(es). In the Control trial, Ve
      increased as T(es) increased from 37.0 degrees C to 38.6 degrees C after the
      onset of exercise. In the Preheating trial, Ve increased from the initially
      elevated levels of T(es) (from 37.6 to 38.6 degrees C) and Ve. The sensitivity of
      Ve to increasing T(es) above the threshold for hyperventilation (the slope of the
      T(es)-Ve relation) did not significantly vary across trials (Precooling trial =
      10.6 +/- 5.9, Control trial = 8.7 +/- 5.1, and Preheating trial = 9.2 +/- 6.9
      L.min(-1). degrees C(-1)). These results suggest that during prolonged submaximal
      exercise at a constant workload in humans, there is a clear core temperature
      threshold for hyperthermic hyperventilation and that the evoked hyperventilatory
      response is unaffected by altering initial core temperature.

PMID- 21957165
TI  - Evidence for the role of hindbrain orexin-1 receptors in the control of meal
      size.
AB  - Hypothalamic orexin neurons project to the hindbrain, and 4th-ventricle
      intracerebroventricular (4th-icv) injection of orexin-A treatment increases food
      intake. We assessed the effects of hindbrain orexin-A and the orexin-1-receptor
      antagonist SB334867 on meal pattern in rats consuming standard chow. When
      injected 4th-icv shortly before dark onset, lower doses of orexin-A increased
      food intake over a 2-h period by increasing the size of the first meal relative
      to vehicle, whereas the highest dose increased food intake by causing the second
      meal to be taken sooner. Conversely, hindbrain SB334867 reduced food intake by
      decreasing the size of the first meal of the dark phase. We also examined the
      effects of 4th-icv orexin-A and SB334867 on locomotor activity. Only the highest
      dose of orexin-A increased activity, and SB334867 had no effect. In addition,
      hindbrain SB334867 induced c-Fos in the nucleus of the solitary tract. These data
      support the suggestion that endogenous hindbrain orexin-A acts to limit
      satiation. Both orexin-A and the pancreatic satiation hormone amylin require an
      intact area postrema to affect food intake, so we asked whether 4th-icv orexin-A
      impairs the satiating effect of peripheral amylin treatment. Amylin reduced the
      size of the first meal of the dark cycle when rats were pretreated with 4th-icv
      saline, yet amylin was ineffective after 4th-icv orexin-A pretreatment. Using
      double-label immunohistochemistry, we determined that some orexin-A fibers in the
      area postrema are located in proximity to amylin-responsive neurons. Therefore,
      hindbrain orexin-A may increase food intake, in part, by reducing the ability of
      rats to respond to amylin during a meal.

PMID- 21957166
TI  - Protein kinase Calpha activity is important for contraction-induced FXYD1
      phosphorylation in skeletal muscle.
AB  - Exercise-induced phosphorylation of FXYD1 is a potential important regulator of
      Na(+)-K(+)-pump activity. It was investigated whether skeletal muscle
      contractions induce phosphorylation of FXYD1 and whether protein kinase Calpha
      (PKCalpha) activity is a prerequisite for this possible mechanism. In part 1,
      human muscle biopsies were obtained at rest, after 30 s of high-intensity
      exercise (166 +/- 31% of Vo(2max)) and after a subsequent 20 min of moderate
      intensity exercise (79 +/- 8% of Vo(2max)). In general, FXYD1 phosphorylation was
      increased compared with rest both after 30 s (P < 0.05) and 20 min (P < 0.001),
      and more so after 20 min compared with 30 s (P < 0.05). Specifically, FXYD1
      ser63, ser68, and combined ser68 and thr69 phosphorylation were 26-45% higher (P
      < 0.05) after 20 min of exercise than at rest. In part 2, FXYD1 phosphorylation
      was investigated in electrically stimulated soleus and EDL muscles from PKCalpha
      knockout (KO) and wild-type (WT) mice. Contractile activity caused FXYD1 ser68
      phosphorylation to be increased (P < 0.001) in WT soleus muscles but to be
      reduced (P < 0.001) in WT extensor digitorum longus. In contrast, contractile
      activity did not affect FXYD1 ser68 phosphorylation in the KO mice. In
      conclusion, exercise induces FXYD1 phosphorylation at multiple sites in human
      skeletal muscle. In mouse muscles, contraction-induced changes in FXYD1 ser68
      phosphorylation are fiber-type specific and dependent on PKCalpha activity.

PMID- 21957167
TI  - Disclosure of clinical trial results when product development is abandoned.
AB  - Currently, sponsors are not required to report the outcomes of clinical research
      on drugs or devices that do not lead to an approved product. Consequently, the
      public cannot benefit from scientific information derived from all failed or
      abandoned drugs and devices. Provisions in the U.S. Food and Drug Administration
      Amendments Act of 2007 provide an opportunity for the Department of Health and
      Human Services to rectify this situation. By reporting the results of clinical
      trials of abandoned products in a publicly accessible database and in the peer
      reviewed journal literature, sponsors would satisfy a core ethical obligation of
      clinical research and enhance translational science.

PMID- 21957169
TI  - Creating the future biomedical research workforce.
AB  - As an NIH task force ponders the future of the U.S. biomedical research
      workforce, clinical and translational scientists can contribute crucial insights
      and should share comments by 7 October 2011.

PMID- 21957171
TI  - Translational neuroscience of schizophrenia: seeking a meeting of minds between
      mouse and man.
AB  - Understanding the etiology of developmental brain disorders such as schizophrenia
      is critical for achieving advances in treatment and requires new research
      strategies that control for individual variation in genetic background,
      environmental challenges, and expression of phenotype. SYSGENET, a European
      systems genetics network for the study of complex genetic human diseases with
      mouse genetic reference populations, brought together in Helsinki a cross
      disciplinary group of clinical and basic scientists and mouse geneticists to
      debate, formulate, and prioritize a strategy for future research based on mouse
      models. The main conclusions of this meeting are summarized here.

PMID- 21957170
TI  - Translating glutamate: from pathophysiology to treatment.
AB  - The neurotransmitter glutamate is the primary excitatory neurotransmitter in
      mammalian brain and is responsible for most corticocortical and corticofugal
      neurotransmission. Disturbances in glutamatergic function have been implicated in
      the pathophysiology of several neuropsychiatric disorders-including
      schizophrenia, drug abuse and addiction, autism, and depression-that were until
      recently poorly understood. Nevertheless, improvements in basic information
      regarding these disorders have yet to translate into Food and Drug Administration
      approved treatments. Barriers to translation include the need not only for
      improved compounds but also for improved biomarkers sensitive to both structural
      and functional target engagement and for improved translational models.
      Overcoming these barriers will require unique collaborative arrangements between
      pharma, government, and academia. Here, we review a recent Institute of Medicine
      sponsored meeting, highlighting advances in glutamatergic theories of
      neuropsychiatric illness as well as remaining barriers to treatment development.

PMID- 21957172
TI  - Dendritic cells regulate natural killer cell activation and epithelial injury in
      experimental biliary atresia.
AB  - Biliary atresia is the most common cholangiopathy of childhood. During infancy,
      an idiopathic activation of the neonatal immune system targets the biliary
      epithelium, obstructs bile ducts, and disrupts the anatomic continuity between
      the liver and the intestine. Here, we use a model of virus-induced biliary
      atresia in newborn mice to trace the initiating pathogenic disease mechanisms to
      resident plasmacytoid (pDCs) and conventional (cDCs) dendritic cells. We found
      pDCs to be the most abundant DC population in the livers of newborn mice, and we
      observed pDCs in the livers of infants at the time of diagnosis. In the livers of
      newborn mice, cDCs spontaneously overexpressed the costimulatory molecule CD80
      soon after birth, and pDCs produced the cytokine interleukin-15 (IL-15) in
      response to a virus insult. Both subtypes of primed DCs were required for the
      proliferation of T lymphocytes and the activation of natural killer cells.
      Disruption of this cellular network by depletion of pDCs or blockade of IL-15
      signaling in mice in vivo prevented epithelial injury, maintained anatomic
      continuity of the bile duct, and promoted long-term survival. These findings
      identify cellular triggers of biliary injury and have implications for future
      therapies to block the progression of biliary atresia and liver disease.

PMID- 21957173
TI  - Computationally generated cardiac biomarkers for risk stratification after acute
      coronary syndrome.
AB  - The existing tools for estimating the risk of death in patients after they
      experience acute coronary syndrome are commonly based on echocardiography and
      clinical risk scores (for example, the TIMI risk score). These identify a small
      group of high-risk patients who account for only a minority of the deaths that
      occur in patients after acute coronary syndrome. Here, we investigated the use of
      three computationally generated cardiac biomarkers for risk stratification in
      this population: morphologic variability (MV), symbolic mismatch (SM), and heart
      rate motifs (HRM). We derived these biomarkers from time-series analyses of
      continuous electrocardiographic data collected from patients in the TIMI
      DISPERSE2 clinical trial through machine learning and data mining methods
      designed to extract information that is difficult to visualize directly in these
      data. We evaluated these biomarkers in a blinded, prespecified, and fully
      automated study on more than 4500 patients in the MERLIN-TIMI36 (Metabolic
      Efficiency with Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary
      Syndrome-Thrombolysis in Myocardial Infarction 36) clinical trial. Our results
      showed a strong association between all three computationally generated cardiac
      biomarkers and cardiovascular death in the MERLIN-TIMI36 trial over a 2-year
      period after acute coronary syndrome. Moreover, the information in each of these
      biomarkers was independent of the information in the others and independent of
      the information provided by existing clinical risk scores, electrocardiographic
      metrics, and echocardiography. The addition of MV, SM, and HRM to existing
      metrics significantly improved model discrimination, as well as the precision and
      recall of prediction rules based on left ventricular ejection fraction. These
      biomarkers can be extracted from data that are routinely captured from patients
      with acute coronary syndrome and will allow for more accurate risk stratification
      and potentially for better patient treatment.

PMID- 21957174
TI  - Reversible cardiac conduction block and defibrillation with high-frequency
      electric field.
AB  - Electrical impulse propagation is an essential function in cardiac, skeletal
      muscle, and nervous tissue. Abnormalities in cardiac impulse propagation underlie
      lethal reentrant arrhythmias, including ventricular fibrillation. Temporary
      propagation block throughout the ventricular myocardium could possibly terminate
      these arrhythmias. Electrical stimulation has been applied to nervous tissue to
      cause reversible conduction block, but has not been explored sufficiently in
      cardiac tissue. We show that reversible propagation block can be achieved in
      cardiac tissue by holding myocardial cells in a refractory state for a designated
      period of time by applying a sustained sinusoidal high-frequency alternating
      current (HFAC); in doing so, reentrant arrhythmias are terminated. We demonstrate
      proof of concept using several models, including optically mapped monolayers of
      neonatal rat ventricular cardiomyocytes, Langendorff-perfused guinea pig and
      rabbit hearts, intact anesthetized adult rabbits, and computer simulations of
      whole-heart impulse propagation. HFAC may be an effective and potentially safer
      alternative to direct current application, currently used to treat ventricular
      fibrillation.

PMID- 21957175
TI  - INK4a deletion results in improved kidney regeneration and decreased capillary
      rarefaction after ischemia-reperfusion injury.
AB  - The molecular mechanisms that lead to tubular atrophy, capillary loss, and
      fibrosis following acute kidney injury are not very clear but may involve cell
      cycle inhibition by increased expression of cyclin kinase inhibitors. The
      INK4a/ARF locus encodes overlapping genes for two proteins, a cyclin kinase
      inhibitor, p16(INK4a), and a p53 stabilizer, p19(ARF), from independent
      promoters. To determine if decreased INK4a gene expression results in improved
      kidney regeneration, INK4a knockout (KO) and wild-type (WT) mice were subjected
      to ischemia-reperfusion injury (IRI). p16(INK4a) and p19(ARF) levels were
      increased markedly in WT mice at 1-28 days after injury. Kidneys were examined to
      determine the localization and levels of p16(INK4a), apoptosis, cell
      proliferation, and capillary rarefaction. KO mice displayed decreased tubular
      cell apoptosis, increased cell proliferation, and lower creatinine levels after
      injury. KO mice had significantly higher capillary density compared with WT mice
      at 14-42 days after IRI. Plasma granulocyte colony-stimulating factor (G-CSF)
      increased after ischemia in both WT and KO mice and was elevated markedly in KO
      compared with WT mice. KO kidney digests contained higher counts of Gr
      1(+)/Cd11b(+) myeloid cells by flow cytometry. KO mice treated with a Gr-1
      depleting antibody displayed reduced vascular endothelial growth factor mRNA,
      plasma G-CSF, and capillary density, and an increase in serum creatinine and
      medullary myofibroblasts, compared with untreated KO mice 14 days after ischemia.
      The anti-angiogenic effect of Gr-1 depletion in KO mice was confirmed by Matrigel
      angiogenesis assays. These results suggest that the absence of p16(INK4a) and
      p19(ARF) following IRI has a protective effect on the kidney through improved
      epithelial and microvascular repair, in part by enhancing the mobilization of
      myeloid cells into the kidney.

PMID- 21957176
TI  - Mast cells are required for the development of renal fibrosis in the rodent
      unilateral ureteral obstruction model.
AB  - Mast cells are associated with inflammation and fibrosis. Whether they protect
      against or contribute to renal fibrosis is unclear. Based on our previous
      findings that mast cells can express and secrete active renin, and that
      angiotensin (ANG II) is profibrotic, we hypothesized that mast cells play a
      critical role in tubulointerstitial fibrosis. We tested this hypothesis in the 14
      day unilateral ureteral obstruction (UUO) model in rats and mast cell-deficient
      (MCD) mice (WBB6F1-W/Wv) and their congenic controls (CC). In the 14-day UUO rat
      kidney, mast cell number is increased and they express active renin. Stabilizing
      mast cells in vivo with administration of cromolyn sodium attenuated the
      development of tubulointerstitial fibrosis, which was confirmed by measuring
      newly synthesized pepsin-soluble collagen and blind scoring of fixed trichrome
      stained kidney sections accompanied by spectral analysis. Fibrosis was absent in
      UUO kidneys from MCD mice unlike that observed in the CC mice. Losartan treatment
      reduced the fibrosis in the CC UUO kidneys. The effects of mast cell
      degranulation and renin release were tested in the isolated, perfused kidney
      preparation. Mast cell degranulation led to renin-dependent protracted flow
      recovery. This demonstrates that mast cell renin is active in situ and the
      ensuing ANG II can modulate intrarenal vascular resistance in the UUO kidney.
      Collectively, the data demonstrate that mast cells are critical to the
      development of renal fibrosis in the 14-day UUO kidney. Since renin is present in
      human kidney mast cells, our work identifies potential targets in the treatment
      of renal fibrosis.

PMID- 21957177
TI  - AMPK protects proximal tubular cells from stress-induced apoptosis by an ATP
      independent mechanism: potential role of Akt activation.
AB  - We examined the role of AMP-activated protein kinase (AMPK) in modulating the
      viability of cultured kidney proximal tubular cells subjected to metabolic stress
      induced by either dextrose deprivation, inhibition of glycolysis, or inhibition
      of mitochondrial respiration. We used BU.MPT cells, a conditionally immortalized
      kidney epithelial cell line derived from the proximal tubules of transgenic mice
      bearing a temperature-sensitive mutation of the simian virus 40 large-tumor
      antigen. All three forms of metabolic stress increased the phosphorylation and
      activity of AMPK. Activation of AMPK led to changes in the phosphorylation of two
      downstream targets of AMPK, acetyl coenzyme A carboxylase and p70 S6 kinase.
      Inhibition of AMPK, either pharmacologically with compound C (CC) or by gene
      silencing, significantly increased the amount of apoptosis in response to all
      three forms of metabolic stress. Although the amount of apoptosis was directly
      related to the severity of ATP depletion, inhibition of AMPK had no effect on
      cellular ATP levels. Notably, metabolic stress increased the phosphorylation and
      activity of Akt. Furthermore, inhibition of AMPK, with CC or gene silencing,
      abrogated the ability of metabolic stress to activate Akt. The augmentation of
      apoptosis induced by inhibition of AMPK was comparable to that induced by
      inhibition of Akt. We conclude that activation of AMPK following acute metabolic
      stress plays a major role in promoting the viability of cultured proximal tubular
      cells. Protection by AMPK appears to be due not to AMPK-mediated conservation of
      cell energy stores, but rather, at least in part, to AMPK-mediated activation of
      Akt.

PMID- 21957179
TI  - Effect of combining an ACE inhibitor and a VDR activator on glomerulosclerosis,
      proteinuria, and renal oxidative stress in uremic rats.
AB  - Angiotensin-converting enzyme (ACE) inhibitors ameliorate the progression of
      renal disease. In combination with vitamin D receptor activators, they provide
      additional benefits. In the present study, uremic (U) rats were treated as
      follows: U+vehicle (UC), U+enalapril (UE; 25 mg/l in drinking water),
      U+paricalcitol (UP; 0.8 MUg/kg ip, 3 * wk), or U+enalapril+paricalcitol (UEP).
      Despite hypertension in UP rats, proteinuria decreased by 32% vs. UC rats.
      Enalapril alone, or in combination with paricalcitol, further decreased
      proteinuria (~70%). Glomerulosclerosis and interstitial infiltration increased in
      UC rats. Paricalcitol and enalapril inhibited this. The increase in cardiac
      atrial natriuretic peptide (ANP) seen in UC rats was significantly decreased by
      paricalcitol. Enalapril produced a more dramatic reduction in ANP. Renal
      oxidative stress plays a critical role in inflammation and progression of
      sclerosis. The marked increase in p22(phox), a subunit of NADPH oxidase, and
      decrease in endothelial nitric oxide synthase were inhibited in all treated
      groups. Cotreatment with both compounds inhibited the uremia-induced increase in
      proinflammatory inducible nitric oxide synthase (iNOS) and glutathione peroxidase
      activity better than either compound alone. Glutathione reductase was also
      increased in UE and UP rats vs. UC. Kidney 4-hydroxynonenal was significantly
      increased in the UC group compared with the normal group. Combined treatment with
      both compounds significantly blunted this increase, P < 0.05, while either
      compound alone had no effect. Additionally, the expression of Mn-SOD was
      increased and CuZn-SOD decreased by uremia. This was ameliorated in all treatment
      groups. Cotreatment with enalapril and paricalcitol had an additive effect in
      increasing CuZn-SOD expression. In conclusion, like enalapril, paricalcitol alone
      can improve proteinuria, glomerulosclerosis, and interstitial infiltration and
      reduce renal oxidative stress. The effects of paricalcitol may be amplified when
      an ACE inhibitor is added since cotreatment with both compounds seems to have an
      additive effect on ameliorating uremia-induced changes in iNOS and CuZn-SOD
      expression, peroxidase activity, and renal histomorphometry.

PMID- 21957178
TI  - Luminal flow modulates H+-ATPase activity in the cortical collecting duct (CCD).
AB  - Epithelial Na(+) channel (ENaC)-mediated Na(+) absorption and BK channel-mediated
      K(+) secretion in the cortical collecting duct (CCD) are modulated by flow, the
      latter requiring an increase in intracellular Ca(2+) concentration ([Ca(2+)](i)),
      microtubule integrity, and exocytic insertion of preformed channels into the
      apical membrane. As axial flow modulates HCO(3)(-) reabsorption in the proximal
      tubule due to changes in both luminal Na(+)/H(+) exchanger 3 and H(+)-ATPase
      activity (Du Z, Yan Q, Duan Y, Weinbaum S, Weinstein AM, Wang T. Am J Physiol
      Renal Physiol 290: F289-F296, 2006), we sought to test the hypothesis that flow
      also regulates H(+)-ATPase activity in the CCD. H(+)-ATPase activity was assayed
      in individually identified cells in microperfused CCDs isolated from New Zealand
      White rabbits, loaded with the pH-sensitive dye BCECF, and then subjected to an
      acute intracellular acid load (NH(4)Cl prepulse technique). H(+)-ATPase activity
      was defined as the initial rate of bafilomycin-inhibitable cell pH (pH(i))
      recovery in the absence of luminal K(+), bilateral Na(+), and CO(2)/HCO(3)(-),
      from a nadir pH of ~6.2. We found that 1) an increase in luminal flow rate from
      ~1 to 5 nl.min(-1).mm(-1) stimulated H(+)-ATPase activity, 2) flow-stimulated
      H(+) pumping was Ca(2+) dependent and required microtubule integrity, and 3)
      basal and flow-stimulated pH(i) recovery was detected in cells that labeled with
      the apical principal cell marker rhodamine Dolichos biflorus agglutinin as well
      as cells that did not. We conclude that luminal flow modulates H(+)-ATPase
      activity in the rabbit CCD and that H(+)-ATPases therein are present in both
      principal and intercalated cells.

PMID- 21957182
TI  - Preface for JCOG review series.

PMID- 21957181
TI  - Epidemiology of Down syndrome: new insight into the multidimensional interactions
      among genetic and environmental risk factors in the oocyte.
AB  - Down syndrome birth is attributable to multiple maternal risk factors that
      include both genetic and environmental challenges, but there is limited
      understanding of the complicated interactions among these factors. In the present
      study, a case-control analysis of approximately 400 infants with or without
      suspected Down syndrome reported between 2003 and 2009 and their parents in and
      around Kolkata, India, was conducted. Maternal exposure to 2 environmental risk
      factors (smokeless chewing tobacco and oral contraceptive pills) was recorded,
      and families were genotyped with microsatellite markers to establish the origin
      of nondisjunction errors as well as recombination patterns of nondisjoined
      chromosome 21. With logistic regression models, the possible interactions among
      all of these risk factors, as well as with maternal age, were explored. Smokeless
      chewing tobacco was associated with significant risk for meiosis II
      nondisjunction and achiasmate (nonexchange) meiosis I error among young mothers.
      By contrast, the risk due to oral contraceptive pills was associated with older
      mothers. Study results suggest that the chewing tobacco risk factor operates
      independently of the maternal age effect, whereas contraceptive pill-related risk
      may interact with or exacerbate age-related risk. Moreover, both risk factors,
      when present together, exhibited a strong age-dependent effect.

PMID- 21957183
TI  - A case of esophageal spindle cell carcinoma.

PMID- 21957184
TI  - Time trends in breast cancer mortality between 1950 and 2008 in Japan, USA and
      Europe based on the WHO mortality database.

PMID- 21957188
TI  - Transforming growth factor beta 1 induces tight junction disruptions and loss of
      transepithelial resistance across porcine vas deferens epithelial cells.
AB  - Epithelial cells lining the male excurrent duct contribute to male fertility by
      employing a number of physiological mechanisms that generate a luminal
      microenvironment conducive to spermatozoa maturation and storage. Among these
      mechanisms, male duct epithelia establish intercellular tight junctions that
      constitute a barrier to paracellular diffusion of water, solutes, large
      molecules, and cells. Mechanisms regulating the male duct epithelial barrier
      remain unidentified. Transforming growth factor beta (TGFB) is a regulatory
      cytokine present in high concentrations in human semen. This study examined
      whether TGFB has any effects on epithelial function exhibited by primary cultures
      of porcine vas deferens epithelia. TGFB1 exposure caused a 70%-99% decrease in
      basal transepithelial electrical resistance (R(TE), a sensitive indicator of
      barrier integrity), while a significant decrease in anion secretory response to
      forskolin was detected at the highest levels of TGFB1 exposure employed.
      SB431542, a selective TGFB receptor I (TGFBR1) inhibitor, prevented decreases in
      barrier function. Results also demonstrated that TGFB1 exposure modifies the
      distribution pattern of tight junction proteins occludin and claudin 7. TGFBR1 is
      localized at the apical border of the native porcine vas deferens epithelium.
      Pharmacological inhibition of mitogen-activated protein kinase (MAPK) 11 (also
      known as p38-MAPK) did not alter the effect of TGFB1 on R(TE) significantly.
      These data suggest that epithelia lining the vas deferens are subject to
      disruptions in the physical barrier if active TGFB becomes bioavailable in the
      luminal fluid, which might be expected to compromise fertility.

PMID- 21957189
TI  - Expression patterns of poliovirus receptor, erythrocyte protein band 4.1-like 3,
      regulator of g-protein signaling 11, and oxytocin receptor in mouse ovarian cells
      during follicle growth and early luteinization in vitro and in vivo.
AB  - Poliovirus receptor (Pvr), erythrocyte protein band 4.1-like 3 (Epb4.1l3),
      regulator of G-protein signaling 11 (Rgs11), and oxytocin receptor (Oxtr)
      expression were quantified in in vitro- and in vivo-grown mouse follicles. The
      expression of all genes was increased during antral growth in in vitro-grown
      cumulus cells, whereas only Rgs11 and Oxtr were increased and Pvr and Epb4.1l3
      were decreased in in vivo grown cumulus cells. In vivo mural granulosa cells
      showed the highest expression of Pvr, Rgs11, and Oxtr. The in vitro granulosa +
      theca compartment responded to human chorionic gonadotropinduring early
      luteinization by either an upregulation (Pvr, Oxtr) or downregulation (Epb41l3,
      Rgs11). Oocytes expressed Epb4.1l3, not Rgs11, and Pvr only in in vitro-grown
      oocytes. Translation into protein was confirmed for Epb4.1l3 in in vitro-grown
      follicles and in vivo-grown cumulus-oocyte complexes. Protein 4.1B was present
      during antral growth in cumulus, granulosa cells, and oocytes. Hypothetical
      functions of Epb4.1l3 and Pvr involve cell adhesion regulation and Rgs11 could be
      involved in cAMP production in the follicle. Oxtr is known to be important during
      and after the ovulatory stimulus, but, as in bovine, was also regulated during
      folliculogenesis. High expression of Pvr and Epb4.1l3 with culture duration in
      cumulus cells might mark inappropriate differentiation into a mural granulosa
      like cell type and function as negative follicle development marker. Rgs11 and
      Oxtr are both in vivo and in vitro upregulated in cumulus cells during antral
      follicle growth and might be considered positive markers for follicle
      development.

PMID- 21957190
TI  - The Bruce effect in Norway rats.
AB  - Intrauterine implantation of fertilized ova can be blocked by exposing recently
      inseminated females with an unfamiliar male. This selective pregnancy failure,
      designated as the Bruce effect (Bruce, Nature 1959; 184:105), is well studied in
      laboratory mice and has been confirmed in several other rodent species. However,
      no clear information exists concerning this phenomenon in the laboratory rat. The
      present study was conducted to investigate whether or not the Bruce effect exists
      in the rat. Females of two F1 hybrid strains (n(total) = 354) with different MHC
      genotypes (F344BNF1, RT1(lv1/n), and LEWPVGF1, RT1(l/c)) were mated with males of
      their own strain and subsequently exposed during the first 4 days postcoitus
      either to a male of the other hybrid strain or to an unfamiliar male of the same
      strain as the stud. The litter rate of each treatment group was determined. As a
      control, mated females of both strains were reexposed to the stud male to
      determine baseline litter rates. Female rats of both F1 hybrid strains showed a
      significantly lower litter rate when exposed to males of a different strain than
      their stud male, compared to the expected values of birth rates observed in
      control females (F344BNF1: P = 0.017; LEWPVGF1: P = 0.019). In contrast, there
      was no difference between expected and observed litter rates in females of both
      F1 hybrid strains after exposure to an unfamiliar male of the same strain as
      their stud. Our results demonstrate for the first time that the Bruce effect,
      well documented in mice, occurs in the Norway rat.

PMID- 21957191
TI  - Seasonal effect on germinal vesicle-stage bovine oocytes is further expressed by
      alterations in transcript levels in the developing embryos associated with
      reduced developmental competence.
AB  - Physiological perturbations of bovine follicle-enclosed oocytes during the
      lengthy period of follicular development can lead to reduced oocyte developmental
      competence. It is suggested that heat stress-induced alterations in germinal
      vesicle (GV)-stage oocytes are further expressed in the transcriptional levels of
      genes involved in oocyte maturation and early embryonic development. Bovine
      oocytes were collected during cold (December-April) and hot (May-November)
      seasons, matured, fertilized, and cultured in vitro. The percentage of fertilized
      oocytes cleaving to the 2- to 4-cell stage was higher in the cold vs. hot season
      (89.0% +/- 2.63% vs. 75% +/- 2.63%, respectively; P < 0.05), as was the
      percentage of cleaved embryos further developing to blastocysts (26.6% +/- 0.9%
      vs. 10.1% +/- 1.8%, respectively; P < 0.05). Total RNA and poly(A) mRNA of
      oocytes and developing embryos were isolated and subjected to semiquantitative
      and real-time PCR for MOS, GDF9, and POU5F1 genes. In GV-stage oocytes, their
      mRNA levels did not differ between the seasons. However, following maturation,
      mRNA levels were higher in oocytes collected in the cold season (P < 0.05). In 4
      cell-stage embryos, GDF9 and POU5F1 showed opposite mRNA patterns between seasons
      (higher and lower levels, respectively) in the hot season (P < 0.05). In both 8
      cell-stage embryos and blastocysts, POU5F1 expression was lower during the hot
      season (P < 0.05). Exposing the ovarian pool of oocytes to environmental stress
      appears to impair maternal mRNA storage and/or the mechanism of transcription
      renewal, in turn affecting embryo gene expression before and after embryonic
      genome activation. Such impairment might partially explain the carry-over effect
      of summer heat stress on dairy cow conception rates.

PMID- 21957192
TI  - Gone without the WNT: a requirement for WNT5A in germ cell migration and testis
      development.

PMID- 21957193
TI  - Meiotic origins of maternal age-related aneuploidy.
AB  - Chromosome segregation errors in female meiosis lead to aneuploidy in the
      resulting egg and embryo, making them one of the leading genetic causes of
      spontaneous abortions and developmental disabilities in humans. It is known that
      aneuploidy of meiotic origin increases dramatically as women age, and current
      evidence suggests that most errors occur in meiosis I. Several hypotheses
      regarding the cause of maternal age-related aneuploidy have been proposed,
      including recombination errors in early meiosis, a defective spindle assembly
      checkpoint in meiosis I, and deterioration of sister chromatid cohesion with age.
      This review discusses findings in each area, and focuses especially on recent
      studies suggesting that deterioration of cohesion with increasing maternal age is
      a leading cause of age-related aneuploidy.

PMID- 21957194
TI  - Communicating the risk of injury in schoolboy rugby: using Poisson probability as
      an alternative presentation of the epidemiology.
AB  - BACKGROUND: The communication of injury risk in rugby and other sports is
      underdeveloped and parents, children and coaches need to be better informed about
      risk. METHOD: A Poisson distribution was used to transform population based
      incidence of injury into average probabilities of injury to individual players.
      RESULTS: The incidence of injury in schoolboy rugby matches range from 7 to 129.8
      injuries per 1000 player-hours; these rates translate to average probabilities of
      injury to a player of between 12% and 90% over a season. CONCLUSION: Incidence of
      injury and average probabilities of injury over a season should be published
      together in all future epidemiological studies on school rugby and other sports.
      More research is required on informing and communicating injury risks to parents,
      staff and children and how it affects monitoring, decision making and prevention
      strategies.

PMID- 21957195
TI  - Functional inhibition of osteoblastic cells in an in vivo mouse model of myeloid
      leukemia.
AB  - Pancytopenia is a major cause of morbidity in acute myeloid leukemia (AML), yet
      its cause is unclear. Normal osteoblastic cells have been shown to support
      hematopoiesis. To define the effects of leukemia on osteoblastic cells, we used
      an immunocompetent murine model of AML. Leukemic mice had inhibition of
      osteoblastic cells, with decreased serum levels of the bone formation marker
      osteocalcin. Osteoprogenitor cells and endosteal-lining osteopontin(+) cells were
      reduced, and osteocalcin mRNA in CD45(-) marrow cells was diminished. This
      resulted in severe loss of mineralized bone. Osteoclasts were only transiently
      increased without significant increases in bone resorption, and their inhibition
      only partially rescued leukemia-induced bone loss. In vitro data suggested that a
      leukemia-derived secreted factor inhibited osteoblastic cells. Because the
      chemokine CCL-3 was recently reported to inhibit osteoblastic function in
      myeloma, we tested its expression in our model and in AML patients. Consistent
      with its potential novel role in leukemic-dependent bone loss, CCL-3 mRNA was
      significantly increased in malignant marrow cells from leukemic mice and from
      samples from AML patients. Based on these results, we propose that therapeutic
      mitigation of leukemia-induced uncoupling of osteoblastic and osteoclastic cells
      may represent a novel approach to promote normal hematopoiesis in patients with
      myeloid neoplasms.

PMID- 21957196
TI  - Molecular characterization of seipin and its mutants: implications for seipin in
      triacylglycerol synthesis.
AB  - The human lipodystrophy gene product Berardinelli-Seip congenital lipodystrophy
      2/seipin has been implicated in adipocyte differentiation, lipid droplet (LD)
      formation, and motor neuron development. However, the molecular function of
      seipin and its disease-causing mutants remains to be elucidated. Here, we
      characterize seipin and its mis-sense mutants: N88S/S90L (both linked to
      motoneuron disorders) and A212P (linked to lipodystrophy) in cultured mammalian
      cells. Knocking down seipin significantly increases oleate incorporation into
      triacylglycerol (TAG) and the steady state level of TAG, and induces the
      proliferation and clustering of small LDs. By contrast, overexpression of seipin
      reduces TAG synthesis, leading to decreased formation of LDs. Expression of the
      A212P mutant, however, had little effect on LD biogenesis. Surprisingly,
      expression of N88S or S90L causes the formation of many small LDs reminiscent of
      seipin deficient cells. This dominant-negative effect may be due to the N88S/S90L
      induced formation of inclusions where wild-type seipin can be trapped.
      Importantly, coexpression of wild-type seipin and the N88S or S90L mutant can
      significantly reduce the formation of inclusions. Finally, we demonstrate that
      seipin can interact with itself and its mutant forms. Our results provide
      important insights into the biochemical characteristics of seipin and its mis
      sense mutants, and suggest that seipin may function to inhibit lipogenesis.

PMID- 21957197
TI  - Evacetrapib is a novel, potent, and selective inhibitor of cholesteryl ester
      transfer protein that elevates HDL cholesterol without inducing aldosterone or
      increasing blood pressure.
AB  - Cholesteryl ester transfer protein (CETP) catalyses the exchange of cholesteryl
      ester and triglyceride between HDL and apoB containing lipoprotein particles. The
      role of CETP in modulating plasma HDL cholesterol levels in humans is well
      established and there have been significant efforts to develop CETP inhibitors to
      increase HDL cholesterol for the treatment of coronary artery disease. These
      efforts, however, have been hampered by the fact that most CETP inhibitors either
      have low potency or have undesirable side effects. In this study, we describe a
      novel benzazepine compound evacetrapib (LY2484595), which is a potent and
      selective inhibitor of CETP both in vitro and in vivo. Evacetrapib inhibited
      human recombinant CETP protein (5.5 nM IC(50)) and CETP activity in human plasma
      (36 nM IC(50)) in vitro. In double transgenic mice expressing human CETP and
      apoAI, evacetrapib exhibited an ex vivo CETP inhibition ED(50) of less than 5
      mg/kg at 8 h post oral dose and significantly elevated HDL cholesterol.
      Importantly, no blood pressure elevation was observed in rats dosed with
      evacetrapib at high exposure multiples compared with the positive control,
      torcetrapib. In addition, in a human adrenal cortical carcinoma cell line (H295R
      cells), evacetrapib did not induce aldosterone or cortisol biosynthesis whereas
      torcetrapib dramatically induced aldosterone and cortisol biosynthesis. Our data
      indicate that evacetrapib is a potent and selective CETP inhibitor without
      torcetrapib-like off-target liabilities. Evacetrapib is currently in phase II
      clinical development.

PMID- 21957198
TI  - A biochemical fluorometric method for assessing the oxidative properties of HDL.
AB  - Most current assays of HDL functional properties are cell-based. We have
      developed a fluorometric biochemical assay based on the oxidation of
      dihydrorhodamine 123 (DHR) by HDL. This cell-free assay assesses the intrinsic
      ability of HDL to be oxidized by measuring increasing fluorescence due to DHR
      oxidation over time. The assay distinguishes the oxidative potential of HDL taken
      from different persons, and the results are reproducible. Direct comparison of
      this measurement correlated well with results obtained using a validated cell
      based assay (r(2) = 0.62, P < 0.001). The assay can be scaled from a 96-well
      format to a 384-well format and, therefore, is suitable for high-throughput
      implementation. This new fluorometric method offers an inexpensive, accurate, and
      rapid means for determining the oxidative properties of HDL that is applicable to
      large-scale clinical studies.

PMID- 21957199
TI  - A sensitive assay for ABCA1-mediated cholesterol efflux using BODIPY-cholesterol.
AB  - Studies have shown a negative association between cellular cholesterol efflux and
      coronary artery disease (CAD). Standard protocol for quantitating cholesterol
      efflux involves labeling cells with [(3)H]cholesterol and measuring release of
      the labeled sterol. Using [(3)H]cholesterol is not ideal for the development of a
      high-throughput assay to screen large numbers of serum as would be required in
      studying the link between efflux and CAD. We compared efflux using a fluorescent
      sterol (boron dipyrromethene difluoride linked to sterol carbon-24, BODIPY
      cholesterol) with that of [(3)H]cholesterol in J774 macrophages. Fractional
      efflux of BODIPY-cholesterol was significantly higher than that of
      [(3)H]cholesterol when apo A-I, HDL(3), or 2% apoB-depleted human serum were used
      as acceptors. BODIPY-cholesterol efflux correlated significantly with
      [(3)H]cholesterol efflux (p < 0.0001) when apoB-depleted sera were used. The
      BODIPY-cholesterol efflux correlated significantly with prebeta-1 (r(2) = 0.6)
      but not with total HDL-cholesterol. Reproducibility of the BODIPY-cholesterol
      efflux assay was excellent between weeks (r(2) = 0.98, inter-assay CV = 3.31%).
      These studies demonstrate that BODIPY-cholesterol provides an efficient
      measurement of efflux compared with [(3)H]cholesterol and is a sensitive probe
      for ABCA1-mediated efflux. The increased sensitivity of BODIPY-cholesterol assay
      coupled with the simplicity of measuring fluorescence results in a sensitive,
      high-throughput assay that can screen large numbers of sera, and thus establish
      the relationship between cholesterol efflux and atherosclerosis.

PMID- 21957200
TI  - LDL-apheresis depletes apoE-HDL and pre-beta1-HDL in familial
      hypercholesterolemia: relevance to atheroprotection.
AB  - Subnormal HDL-cholesterol (HDL-C) and apolipoprotein (apo)AI levels are
      characteristic of familial hypercholesterolemia (FH), reflecting perturbed
      intravascular metabolism with compositional anomalies in HDL particles, including
      apoE enrichment. Does LDL-apheresis, which reduces HDL-cholesterol, apoAI, and
      apoE by adsorption, induce selective changes in HDL subpopulations, with
      relevance to atheroprotection? Five HDL subpopulations were fractionated from pre
      and post-LDL-apheresis plasmas of normotriglyceridemic FH subjects (n = 11) on
      regular LDL-apheresis (>2 years). Apheresis lowered both plasma apoE (-62%) and
      apoAI (-16%) levels, with preferential, genotype-independent reduction in apoE.
      The mass ratio of HDL2:HDL3 was lowered from ~1:1 to 0.72:1 by apheresis,
      reflecting selective removal of HDL2 mass (80% of total HDL adsorbed). Pre-LDL
      apheresis, HDL2 subpopulations were markedly enriched in apoE, consistent with ~1
      copy of apoE per 4 HDL particles. Large amounts (50-66%) of apoE-HDL were removed
      by apheresis, preferentially in the HDL2b subfraction (-50%); minor absolute
      amounts of apoE-HDL were removed from HDL3 subfractions. Furthermore, pre-beta1
      HDL particle levels were subnormal following removal (-53%) upon apheresis,
      suggesting that cellular cholesterol efflux may be defective in the immediate
      postapheresis period. In LDL-receptor (LDL-R) deficiency, LDL-apheresis may
      enhance flux through the reverse cholesterol transport pathway and equally
      attenuate potential biglycan-mediated deposition of apoE-HDL in the arterial
      matrix.

PMID- 21957201
TI  - Reductive metabolism increases the proinflammatory activity of aldehyde
      phospholipids.
AB  - The generation of oxidized phospholipids in lipoproteins has been linked to
      vascular inflammation in atherosclerotic lesions. Products of phospholipid
      oxidation increase endothelial activation; however, their effects on macrophages
      are poorly understood, and it is unclear whether these effects are regulated by
      the biochemical pathways that metabolize oxidized phospholipids. We found that
      incubation of 1-palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC)
      with THP-1-derived macrophages upregulated the expression of cytokine genes,
      including granulocyte/macrophage colony-stimulating factor (GM-CSF), tumor
      necrosis factor (TNF)-alpha, monocyte chemotactic protein 1 (MCP-1), interleukin
      (IL)-1beta, IL-6, and IL-8. In these cells, reagent POVPC was either hydrolyzed
      to lyso-phosphatidylcholine (lyso-PC) or reduced to 1-palmitoyl-2-(5-hydroxy
      valeroyl)-sn-glycero-3-phosphocholine (PHVPC). Treatment with the phospholipase
      A(2) (PLA(2)) inhibitor, pefabloc, decreased POVPC hydrolysis and increased PHVPC
      accumulation. Pefabloc also increased the induction of cytokine genes in POVPC
      treated cells. In contrast, PHVPC accumulation and cytokine production were
      decreased upon treatment with the aldose reductase (AR) inhibitor, tolrestat. In
      comparison with POVPC, lyso-PC led to 2- to 3-fold greater and PHVPC 10- to 100
      fold greater induction of cytokine genes. POVPC-induced cytokine gene induction
      was prevented in bone-marrow derived macrophages from AR-null mice. These results
      indicate that although hydrolysis is the major pathway of metabolism, reduction
      further increases the proinflammatory responses to POVPC. Thus, vascular
      inflammation in atherosclerotic lesions is likely to be regulated by metabolism
      of phospholipid aldehydes in macrophages.

PMID- 21957202
TI  - Nascent HDL formation by hepatocytes is reduced by the concerted action of serum
      amyloid A and endothelial lipase.
AB  - Inflammation is associated with significant decreases in plasma HDL-cholesterol
      (HDL-C) and apoA-I levels. Endothelial lipase (EL) is known to be an important
      determinant of HDL-C in mice and in humans and is upregulated during
      inflammation. In this study, we investigated whether serum amyloid A (SAA), an
      HDL apolipoprotein highly induced during inflammation, alters the ability of EL
      to metabolize HDL. We determined that EL hydrolyzes SAA-enriched HDL in vitro
      without liberating lipid-free apoA-I. Coexpression of SAA and EL in mice by
      adenoviral vector produced a significantly greater reduction in HDL-C and apoA-I
      than a corresponding level of expression of either SAA or EL alone. The loss of
      HDL occurred without any evidence of HDL remodeling to smaller particles that
      would be expected to have more rapid turnover. Studies with primary hepatocytes
      demonstrated that coexpression of SAA and EL markedly impeded ABCA1-mediated
      lipidation of apoA-I to form nascent HDL. Our findings suggest that a reduction
      in nascent HDL formation may be partly responsible for reduced HDL-C during
      inflammation when both EL and SAA are known to be upregulated.

PMID- 21957204
TI  - Do we miss depressive disorders and suicidal behaviours in clinical practice?
AB  - This study involved a detailed standardized initial research assessment which was
      carried out with 100 young people aged 12-15 years newly referred to a child and
      adolescent mental health service. The assessment involved the K-SADS interview
      with the young person and their parent, the Strengths and Difficulties
      Questionnaire, the Clinical Global Impression Scale, and the Children's Global
      Assessment Scale. Diagnoses resulting from these 'research assessments' were
      compared with clinical diagnoses, which were determined by case note analysis and
      discussion with the key clinician. Results showed that a clinical diagnosis of
      depressive disorder was made in only one-third of those who received a 'research
      assessment' diagnosis of depressive disorder, and suicidality was missed in a
      significant proportion of cases. Those with a diagnosis of depressive disorder
      had significantly more problems, more comorbidity, more suicidality and greater
      functional impairment than those without. It is important to keep depression and
      suicidality in mind when assessing young people with complex mental health
      difficulties. Unless specific pointers are sought, it is easy to miss these,
      which may mean that vulnerable young people do not benefit from potentially
      effective treatments.

PMID- 21957203
TI  - Turnover of nonessential fatty acids in cardiolipin from the rat heart.
AB  - Cardiolipin (CL) is a unique phospholipid (PL) found in the mitochondria of
      mammalian cells. CL remodeling is accompanied by turnover of its fatty acid acyl
      groups. Abnormalities in CL remodeling have been found in Barth's syndrome,
      diabetes, and obesity. The objective of this study was to determine nonessential
      fatty acid turnover in CL and phosphatidylethanolamine (PE) in the rat heart in
      vivo. Sprague-Dawley rats were fed either a regular chow or a high-fat diet for
      15 weeks, and consumed 6% deuterium-enriched drinking water as a tracer for 14
      days. CL and PE were extracted from cardiac tissue and isolated by TLC. Fatty
      acids from CL, PE, and plasma were analyzed by GC/MS for deuterium incorporation.
      Results showed oleate and vaccenate turnover were the highest in CL whereas
      palmitate and stearate turnover were low. Among the nonessential fatty acids in
      PE, turnover of stearate and vaccenate were the highest. The high turnover rate
      in vaccenate was unexpected, because vaccenate previously had no known metabolic
      or physiologic function. In conclusion, the similarly high turnover rates of both
      oleate and vaccenate readily suggest that remodeling is an important functional
      aspect of PL metabolism in CL.

PMID- 21957205
TI  - Relationship focused parent training within a dialectical framework: a case
      study.
AB  - There are significant limitations to traditional behavioural parent training
      programmes and research indicates that interventions which incorporate
      relationship factors show superior results. Bidirectional models of the parent
      child relationship provide an initial step for informing the field of parent
      training but more comprehensive models are required and using a dialectical
      framework is proposed. The current case study describes a programme that provided
      a five-week parent training course, with the core concept being finding and
      maintaining balance in the parent-child relationship. Results indicated that
      while two mothers with their three- and four- year-old child showed different
      responses to the therapy, they both reported an improvement in relationship
      factors. It is proposed that this is one of the necessary precursors to
      behavioural change. Limitations and suggestions for further research are
      discussed.

PMID- 21957206
TI  - Depression in older adults.

PMID- 21957207
TI  - Seeking a better world for women and girls.

PMID- 21957208
TI  - Antenatal care for twin and triplet pregnancies: summary of NICE guidance.

PMID- 21957209
TI  - The politics of drug industry sponsorship.

PMID- 21957210
TI  - Manners maketh the doctor.

PMID- 21957211
TI  - Co-lumbo.

PMID- 21957212
TI  - The Health and Social Care Bill: 10 things for the Lords to consider.

PMID- 21957213
TI  - GMTV's Dr Steele is wrong to promote cervical screening in under 25s.

PMID- 21957214
TI  - EU must reform clinical trial regulation, warn medical research bodies.

PMID- 21957215
TI  - GAVI rolls out vaccines against child killers to more countries.

PMID- 21957216
TI  - Annual mammography after breast cancer may improve survival, researchers say.

PMID- 21957217
TI  - Doctors will have a duty to report lapses in patients' basic care.

PMID- 21957218
TI  - Cost of employer provided health insurance double in US in a decade.

PMID- 21957219
TI  - Task-level feedback can explain temporal recruitment of spatially fixed muscle
      synergies throughout postural perturbations.
AB  - Recent evidence suggests that complex spatiotemporal patterns of muscle activity
      can be explained with a low-dimensional set of muscle synergies or M-modes. While
      it is clear that both spatial and temporal aspects of muscle coordination may be
      low dimensional, constraints on spatial versus temporal features of muscle
      coordination likely involve different neural control mechanisms. We hypothesized
      that the low-dimensional spatial and temporal features of muscle coordination are
      independent of each other. We further hypothesized that in reactive feedback
      tasks, spatially fixed muscle coordination patterns-or muscle synergies-are
      hierarchically recruited via time-varying neural commands based on delayed task
      level feedback. We explicitly compared the ability of spatially fixed (SF) versus
      temporally fixed (TF) muscle synergies to reconstruct the entire time course of
      muscle activity during postural responses to anterior-posterior support-surface
      translations. While both SF and TF muscle synergies could account for EMG
      variability in a postural task, SF muscle synergies produced more consistent and
      physiologically interpretable results than TF muscle synergies during postural
      responses to perturbations. Moreover, a majority of SF muscle synergies were
      consistent in structure when extracted from epochs throughout postural responses.
      Temporal patterns of SF muscle synergy recruitment were well-reconstructed by
      delayed feedback of center of mass (CoM) kinematics and reproduced EMG activity
      of multiple muscles. Consistent with the idea that independent and hierarchical
      low-dimensional neural control structures define spatial and temporal patterns of
      muscle activity, our results suggest that CoM kinematics are a task variable used
      to recruit SF muscle synergies for feedback control of balance.

PMID- 21957220
TI  - Persistent activity in a cortical-to-subcortical circuit: bridging the temporal
      gap in trace eyelid conditioning.
AB  - We have addressed the source and nature of the persistent neural activity that
      bridges the stimulus-free gap between the conditioned stimulus (CS) and
      unconditioned stimulus (US) during trace eyelid conditioning. Previous work has
      demonstrated that this persistent activity is necessary for trace eyelid
      conditioning: CS-elicited activity in mossy fiber inputs to the cerebellum does
      not extend into the stimulus-free trace interval, which precludes the cerebellar
      learning that mediates conditioned response expression. In behaving rabbits we
      used in vivo recordings from a region of medial prefrontal cortex (mPFC) that is
      necessary for trace eyelid conditioning to test the hypothesis that neurons there
      generate activity that persists beyond CS offset. These recordings revealed two
      patterns of activity during the trace interval that would enable cerebellar
      learning. Activity in some cells began during the tone CS and persisted to
      overlap with the US, whereas in other cells, activity began during the stimulus
      free trace interval. Injection of anterograde tracers into this same region of
      mPFC revealed dense labeling in the pontine nuclei, where recordings also
      revealed tone-evoked persistent activity during trace conditioning. These data
      suggest a corticopontine pathway that provides an input to the cerebellum during
      trace conditioning trials that bridges the temporal gap between the CS and US to
      engage cerebellar learning. As such, trace eyelid conditioning represents a well
      characterized and experimentally tractable system that can facilitate mechanistic
      analyses of cortical persistent activity and how it is used by downstream brain
      structures to influence behavior.

PMID- 21957221
TI  - Dopaminergic-induced changes in Mauthner cell excitability disrupt prepulse
      inhibition in the startle circuit of goldfish.
AB  - Prepulse inhibition (PPI) is a widespread sensorimotor gating phenomenon
      characterized by a decrease in startle magnitude if a nonstartling stimulus is
      presented 20-1,000 ms before a startling stimulus. Dopaminergic agonists disrupt
      behavioral PPI in various animal models. This provides an important
      neuropharmacological link to schizophrenia patients that typically show PPI
      deficits at distinct (60 ms) prepulse-pulse intervals. Here, we study time
      dependent effects of dopaminergic modulation in the goldfish Mauthner cell (M
      cell) startle network, which shows PPI-like behavioral and physiological startle
      attenuations. The unique experimental accessibility of the M-cell system allows
      investigating the underlying cellular mechanism with physiological stimuli in
      vivo. Our results show that the dopaminergic agonist apomorphine (2 mg/kg body
      wt) reduced synaptic M-cell PPI by 23.6% (n = 18; P = 0.009) for prepulse-pulse
      intervals of 50 ms, whereas other intervals showed no reduction. Consistently,
      application of the dopamine antagonist haloperidol (0.4 mg/kg body wt) restored
      PPI to control level. Current ramp injections while recording M-cell membrane
      potential revealed that apomorphine acts through a postsynaptic, time-dependent
      mechanism by deinactivating a M-cell membrane nonlinearity, effectively
      increasing input resistance close to threshold. This increase is most pronounced
      for prepulse-pulse intervals of 50 ms (47.9%, n = 8; P < 0.05) providing a time
      dependent, cellular mechanism for dopaminergic disruption of PPI. These results
      provide, for the first time, direct evidence of dopaminergic modulation of PPI in
      the elementary startle circuit of vertebrates and reemphasize the potential of
      characterizing temporal aspects of PPI at the physiological level to understand
      its underlying mechanisms.

PMID- 21957222
TI  - Long-term patch recordings from adult spinal neurons herald new era of
      opportunity.
AB  - Recently, Andreas Husch, Nathan Cramer, and Ronald M. Harris-Warrick achieved a
      remarkable breakthrough in patch-clamp recordings of ventral horn neurons in the
      adult spinal cord slice preparation. This landmark study that breaks the "age
      barrier" is titled "Long-duration perforated patch recordings from spinal
      interneurons of adult mice" (Husch et al., in press). In it, the authors
      demonstrate the unprecedented ability to undertake day-long (up to 12 h), and
      utterly stable perforated patch recordings. A description of the methodology is
      detailed in their paper. Here, I give a brief overview before providing context
      to this extraordinary achievement.

PMID- 21957223
TI  - Natural error patterns enable transfer of motor learning to novel contexts.
AB  - Successful behavior demands motor learning to be transferable in some cases
      (e.g., adjusting walking patterns as we develop and age) and context specific in
      others (e.g., learning to walk in high heels). Here we investigated differences
      in motor learning transfer in people learning a new walking pattern on a split
      belt treadmill, where the legs move at different speeds. We hypothesized that
      transfer of the newly acquired walking pattern on the treadmill to natural over
      ground walking might depend on the pattern of errors experienced during learning.
      Error patterns within a person's natural range might be experienced as endogenous
      (i.e., produced by the body), encouraging general adjustments that transfer
      across contexts. On the other hand, larger errors might be experienced as
      exogenous (i.e., produced by the environment), indicating unusual conditions
      requiring context-specific learning. To test this, we manipulated the
      distribution of errors experienced during learning to lie either within or
      outside the normal distribution of walking errors. We found that restriction of
      errors to the natural range produced transfer of the new walking pattern from the
      treadmill to natural walking off the treadmill, while larger errors prevented
      transfer. This result helps explain how transfer of motor learning is controlled,
      and it offers an important strategy for clinical rehabilitation, where transfer
      of motor learning to other contexts is essential.

PMID- 21957224
TI  - Alterations to multisensory and unisensory integration by stimulus competition.
AB  - In environments containing sensory events at competing locations, selecting a
      target for orienting requires prioritization of stimulus values. Although the
      superior colliculus (SC) is causally linked to the stimulus selection process,
      the manner in which SC multisensory integration operates in a competitive
      stimulus environment is unknown. Here we examined how the activity of visual
      auditory SC neurons is affected by placement of a competing target in the
      opposite hemifield, a stimulus configuration that would, in principle, promote
      interhemispheric competition for access to downstream motor circuitry.
      Competitive interactions between the targets were evident in how they altered
      unisensory and multisensory responses of individual neurons. Responses elicited
      by a cross-modal stimulus (multisensory responses) proved to be substantially
      more resistant to competitor-induced depression than were unisensory responses
      (evoked by the component modality-specific stimuli). Similarly, when a cross
      modal stimulus served as the competitor, it exerted considerably more depression
      than did its individual component stimuli, in some cases producing more
      depression than predicted by their linear sum. These findings suggest that
      multisensory integration can help resolve competition among multiple targets by
      enhancing orientation to the location of cross-modal events while simultaneously
      suppressing orientation to events at alternate locations.

PMID- 21957225
TI  - Plasticity of rat motoneuron rhythmic firing properties with varying levels of
      afferent and descending inputs.
AB  - Hindlimb motoneuron excitability was compared among exercise-trained (E),
      sedentary (S), and spinal cord transected (T) Sprague-Dawley rats by examining
      the slope of the frequency-current (F/I) relationship with standard intracellular
      recording techniques in rats anesthetized with ketamine-xylazine. The T group
      included spinal transected and spinal isolated rats; the E animals were either
      spontaneously active (exercise wheel) or treadmill trained; and rats in the S
      group were housed in pairs. An analysis of motoneuron initial [1st interspike
      interval (ISI)], early (mean of 1st three ISIs), and steady-state (mean of last 3
      ISIs) discharge rate slopes resulting from increasing and decreasing 500-ms
      injected square-wave depolarizing current pulses was used to describe rhythmic
      motoneuron properties. The steepest slope occurred in the S group (55.3 +/- 22.2
      Hz/nA), followed by the T group (35.5 +/- 15.3 Hz/nA), while the flattest slope
      was found in the E group (25.4 +/- 10.9 Hz/nA). The steepest steady-state slope
      occurred in the S group but was found to be similar between the T and E groups.
      Furthermore, a spike-frequency adaptation (SFA) index revealed a slower
      adaptation in motoneurons of the E animals only (~40% lower). Finally, evidence
      for a secondary range of firing existed more frequently in the T group (41%)
      compared with the S (12%) and E (31%) groups. The lower F/I slope and lower SFA
      index of motoneurons for E rats may be a result of an increase in Na(+)
      conductance at the initial segment. The results show that motoneuronal rhythmic
      firing behavior is plastic, depending on the volume of daily activation and on
      intact descending pathways.

PMID- 21957226
TI  - Activation of GABAA receptors modulates all stages of mechanoreception in spider
      mechanosensory neurons.
AB  - GABA(A) receptors mediate mainly inhibitory effects, but there are also many
      examples of excitatory effects in both mammalian and invertebrate preparations.
      Here, we aimed to create a complete, quantitative picture of GABA(A)-mediated
      excitation in a mechanosensory neuron where this phenomenon has been well
      established. We used muscimol to activate GABA(A) receptors in spider VS-3
      neurons and measured the dynamic behavior independently and separately at each of
      three stages of mechanoreception (receptor current, receptor potential, and
      action potentials) before and during modulation. We calculated frequency response
      functions between each stage, estimated information as signal entropy, and
      estimated information capacity from coherence. Since coherence is sensitive to
      both noise and nonlinearity, we measured signal-to-noise separately at each stage
      by averaging responses to repeated mechanical inputs. Muscimol depolarized VS-3
      neurons and, after brief inhibition, increased their firing rates. During this
      excitation, we found significant changes at each stage. Receptor current was
      attenuated but became more selective to high frequencies. Membrane impedance and
      time constant fell, favoring higher frequency transmission from receptor current
      to receptor potential. Action potential firing increased and had higher total
      entropy. Information capacity from signal-to-noise was always much higher than
      from coherence, confirming that intracellular noise does not limit signal
      transmission in these neurons. We conclude that GABA(A) receptor activation
      shifts each stage of mechanotransduction to higher frequency sensitivity, while
      the elevated firing rate increases the amount of information that can be encoded.
      These results show that a single neurotransmitter can finely modulate a sensory
      neuron's sensitivity and ability to transmit information.

PMID- 21957227
TI  - Contrasting effects of finger and shoulder interpersonal light touch on standing
      balance.
AB  - Sway is reduced by light nonsupporting touch between parts of the body and a
      fixed surface. This effect is assumed to reflect augmentation of sensory cues for
      sway by point-of-contact reaction forces. It has been shown that movement of the
      contact surface can increase sway relative to an earth-fixed contact. Light touch
      contact with another person, for example, holding hands, affords a moving contact
      due to partner sway. We asked whether interpersonal light touch (IPLT) would
      increase sway relative to standing alone. We expected effects on sway to vary as
      a function of the site of contact and the postural stability of each partner.
      Eight pairs of participants, standing in either normal bipedal or tandem Romberg
      stance with eyes closed and using IPLT (finger to finger or shoulder to shoulder)
      or no contact, provided 4 trials of 30-s duration in each of 12 posture-touch
      combinations. Sway (SD of the rate of change of upper trunk position at C7) was
      reliably less with IPLT compared with no contact, with two exceptions: in normal
      stance, shoulder contact with a partner in tandem stance, and in tandem Romberg
      stance, finger contact with a partner in the same stance, increased sway.
      Otherwise, the reduction in sway was greater with shoulder than with finger
      contact. Measures of interpersonal synchronization based on cross-correlations
      and coherence analysis between the partners' C7 movements suggest different
      control factors operate to reduce sway in IPLT with the hand or shoulder contact.

PMID- 21957228
TI  - Plasticity of spontaneous excitatory and inhibitory synaptic activity in
      morphologically defined vestibular nuclei neurons during early vestibular
      compensation.
AB  - After unilateral peripheral vestibular lesions, the brain plasticity underlying
      early recovery from the static symptoms is not fully understood. Principal cells
      of the chick tangential nucleus offer a subset of morphologically defined
      vestibular nuclei neurons to study functional changes after vestibular lesions.
      Chickens show posture and balance deficits immediately after unilateral
      vestibular ganglionectomy (UVG), but by 3 days most subjects begin to recover,
      although some remain uncompensated. With the use of whole cell voltage-clamp,
      spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs)
      and miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs)
      were recorded from principal cells in brain slices 1 and 3 days after UVG. One
      day after UVG, sEPSC frequency increased on the lesion side and remained elevated
      at 3 days in uncompensated chickens only. Also by 3 days, sIPSC frequency
      increased on the lesion side in all operated chickens due to major increases in
      GABAergic events. Significant change also occurred in decay time of the events.
      To determine whether fluctuations in frequency and kinetics influenced overall
      excitatory or inhibitory synaptic drive, synaptic charge transfer was calculated.
      Principal cells showed significant increase in excitatory synaptic charge
      transfer only on the lesion side of uncompensated chickens. Thus compensation
      continues when synaptic charge transfer is in balance bilaterally. Furthermore,
      excessive excitatory drive in principal cells on the lesion side may prevent
      vestibular compensation. Altogether, this work is important for it defines the
      time course and excitatory and inhibitory nature of changing spontaneous synaptic
      inputs to a morphologically defined subset of vestibular nuclei neurons during
      critical early stages of recovery after UVG.

PMID- 21957229
TI  - pUNISHER: a high-level expression cassette for use with recombinant viral vectors
      for rapid and long term in vivo neuronal expression in the CNS.
AB  - Fast onset and high-level neurospecific transgene expression in vivo is of
      importance for many areas in neuroscience, from basic to translational, and can
      significantly reduce the amount of vector load required to maintain transgene
      expression in vivo. In this study, we tested various cis elements to optimize
      transgene expression at transcriptional, posttranscriptional, and
      posttranslational levels and combined them together to create the high-level
      neuronal transgene expression cassette pUNISHER. Using a second-generation
      adenoviral vector system in combination with the pUNISHER cassette, we
      characterized its rate of onset of detectable expression and levels of expression
      compared with a neurospecific expression cassette driven by the 470-bp human
      synapsin promoter in vitro and in vivo. Our results demonstrate in primary
      neurons that the pUNISHER cassette, in a recombinant adenovirus type 5
      background, led to a faster rate of onset of detectable transgene expression and
      higher level of transgene expression. More importantly, this cassette led to
      highly correlated neuronal expression in vivo and to stable transgene expression
      up to 30 days in the auditory brain stem with no toxicity on the characteristics
      of synaptic transmission and plasticity at the calyx of Held synapse. Thus the
      pUNISHER cassette is an ideal high-level neuronal expression cassette for use in
      vivo for neuroscience applications.

PMID- 21957231
TI  - Time-dependent influence of prior probability: a problem for the drift-diffusion
      model?

PMID- 21957232
TI  - In vivo olfactory model of APP-induced neurodegeneration reveals a reversible
      cell-autonomous function.
AB  - Amyloid precursor protein (APP) has long been linked to the neurodegeneration of
      Alzheimer's disease (AD), but the associated cell death has been difficult to
      capture in vivo, and the role of APP in effecting neuron loss is still unclear.
      Olfactory dysfunction is an early symptom of AD with amyloid pathology in the
      olfactory epithelium correlating well to the brain pathology of AD patients. As
      olfactory sensory neurons (OSNs) regenerate continuously with immature and mature
      OSNs coexisting in the same olfactory epithelium, we sought to use this unique
      system to study APP-induced neurodegeneration. Here we have developed an
      olfactory-based transgenic mouse model that overexpresses humanized APP
      containing familial AD mutations (hAPP) in either mature or immature OSNs, and
      found that despite the absence of extracellular plaques a striking number of
      apoptotic neurons were detected by 3 weeks of age. Importantly, apoptosis was
      restricted to the specific population overexpressing hAPP, either mature or
      immature OSNs, sparing those without hAPP. Interestingly, we observed that this
      widespread neurodegeneration could be rapidly rescued by reducing hAPP expression
      levels in immature neurons. Together, these data argue that overexpressing hAPP
      alone could induce cell-autonomous apoptosis in both mature and immature neurons,
      challenging the notion that amyloid plaques are necessary for neurodegeneration.
      Furthermore, we show that hAPP-induced neurodegeneration is reversible,
      suggesting that AD-related neural loss could potentially be rescued. Thus, we
      propose that this unique in vivo model will not only help determine the
      mechanisms underlying AD-related neurodegeneration but also serve as a platform
      to test possible treatments.

PMID- 21957230
TI  - Silencing of p130cas in ovarian carcinoma: a novel mechanism for tumor cell
      death.
AB  - BACKGROUND: We investigated the clinical and biological significance of p130cas,
      an important cell signaling molecule, in ovarian carcinoma. METHODS: Expression
      of p130cas in ovarian tumors, as assessed by immunohistochemistry, was associated
      with tumor characteristics and patient survival. The effects of p130cas gene
      silencing with small interfering RNAs incorporated into neutral nanoliposomes
      (siRNA-DOPC), alone and in combination with docetaxel, on in vivo tumor growth
      and on tumor cell proliferation (proliferating cell nuclear antigen) and
      apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labeling) were
      examined in mice bearing orthotopic taxane-sensitive (HeyA8 and SKOV3ip1) or
      taxane-resistant (HeyA8-MDR) ovarian tumors (n = 10 per group). To determine the
      specific mechanisms by which p130cas gene silencing abrogates tumor growth, we
      measured cell viability (MTT assay), apoptosis (fluorescence-activated cell
      sorting), autophagy (immunoblotting, fluorescence, and transmission electron
      microscopy), and cell signaling (immunoblotting) in vitro. All statistical tests
      were two-sided. RESULTS: Of 91 ovarian cancer specimens, 70 (76%) had high
      p130cas expression; and 21 (24%) had low p130cas expression. High p130cas
      expression was associated with advanced tumor stage (P < .001) and higher
      residual disease (>1 cm) following primary cytoreduction surgery (P = .007) and
      inversely associated with overall survival and progression-free survival (median
      overall survival: high p130cas expression vs low expression, 2.14 vs 9.1 years,
      difference = 6.96 years, 95% confidence interval = 1.69 to 9.48 years, P < .001;
      median progression-free survival: high p130cas expression vs low expression, 1.04
      vs 2.13 years, difference = 1.09 years, 95% confidence interval = 0.47 to 2.60
      years, P = .01). In mice bearing orthotopically implanted HeyA8 or SKOV3ip1
      ovarian tumors, treatment with p130cas siRNA-DOPC in combination with docetaxel
      chemotherapy resulted in the greatest reduction in tumor growth compared with
      control siRNA therapy (92%-95% reduction in tumor growth; P < .001 for all).
      Compared with control siRNA therapy, p130cas siRNA-DOPC reduced SKOV3ip1 cell
      proliferation (31% reduction, P < .001) and increased apoptosis (143% increase, P
      < .001) in vivo. Increased tumor cell apoptosis may have persisted despite pan
      caspase inhibition by the induction of autophagy and related signaling pathways.
      CONCLUSIONS: Increased p130cas expression is associated with poor clinical
      outcome in human ovarian carcinoma, and p130cas gene silencing decreases tumor
      growth through stimulation of apoptotic and autophagic cell death.

PMID- 21957233
TI  - FXR1P but not FMRP regulates the levels of mammalian brain-specific microRNA-9
      and microRNA-124.
AB  - Mammalian brain-specific miR-9 and miR-124 have been implicated in several
      aspects of neuronal development and function. However, it is not known how their
      expression levels are regulated in vivo. We found that the levels of miR-9 and
      miR-124 are regulated by FXR1P but not by the loss of FXR2P or FMRP in vivo, a
      mouse model of fragile X syndrome. Surprisingly, the levels of miR-9 and miR-124
      are elevated in fmr1/fxr2 double-knock-out mice, in part reflecting
      posttranscriptional upregulation of FXR1P. Indeed, FXR1P is required for
      efficient processing of pre-miR-9 and pre-miR-124 in vitro and forms a complex
      with Dicer and pre-miRNAs. These findings reveal differential roles of FMRP
      family proteins in controlling the expression levels of brain-specific miRNAs.

PMID- 21957234
TI  - Synaptic and extrasynaptic NMDA receptors differentially modulate neuronal
      cyclooxygenase-2 function, lipid peroxidation, and neuroprotection.
AB  - Stimulation of synaptic NMDA receptors (NMDARs) induces neuroprotection, while
      extrasynaptic NMDARs promote excitotoxic cell death. Neuronal expression of
      cyclooxygenase-2 (COX-2) is enhanced by synaptic NMDARs, and although this enzyme
      mediates neuronal functions, COX-2 is also regarded as a key modulator of
      neuroinflammation and is thought to exacerbate excitotoxicity via overproduction
      of prostaglandins. This raises an apparent paradox: synaptic NMDARs are pro
      survival yet are essential for robust neuronal COX-2 expression. We hypothesized
      that stimulation of extrasynaptic NMDARs converts COX-2 signaling from a
      physiological to a potentially pathological process. We combined HPLC
      electrospray ionization-tandem MS-based mediator lipidomics and unbiased image
      analysis in mouse dissociated and organotypic cortical cultures to uncover that
      synaptic and extrasynaptic NMDARs differentially modulate neuronal COX-2
      expression and activity. We show that synaptic NMDARs enhance neuronal COX-2
      expression, while sustained synaptic stimulation limits COX-2 activity by
      suppressing cellular levels of the primary COX-2 substrate, arachidonic acid
      (AA). In contrast, extrasynaptic NMDARs suppress COX-2 expression while
      activating phospholipase A2, which enhances AA levels by hydrolysis of membrane
      phospholipids. Thus, sequential activation of synaptic then extrasynaptic NMDARs
      maximizes COX-2-dependent prostaglandin synthesis. We also show that excitotoxic
      events only drive induction of COX-2 expression through abnormal synaptic network
      excitability. Finally, we show that nonenzymatic lipid peroxidation of
      arachidonic and other polyunsaturated fatty acids is a function of network
      activity history. A new paradigm emerges from our results suggesting that
      pathological COX-2 signaling associated with models of stroke, epilepsy, and
      neurodegeneration requires specific spatiotemporal NMDAR stimulation.

PMID- 21957235
TI  - Homeostatic interactions at the front of migration control the integrity and the
      efficiency of a migratory glial chain.
AB  - In metazoans, cell migration often occurs in a collective manner: the cells move
      while physically and functionally connected to their neighbors. The coordinated
      and timely movement of the cells eventually ensures the proper organization of
      tissues, and deregulation in such a process contributes to the development of
      severe diseases. Thus, understanding the cellular mechanisms underlying
      coordinated cell movement is of great interest in basic and medical science. The
      developing Drosophila wing provides an excellent model to follow the chain
      migration of glial cells in vivo. Cells at the tip of the glial collective have
      been shown to control the timely movement of the chain. In the present study, we
      show that while pioneers trigger chain migration, they cannot move as single
      cells. We also show that isolating cell clusters at the chain tip restores the
      formation of smaller migratory communities. Interestingly, the migratory
      efficiency of these de novo formed communities depends on the number of cells and
      progressively improves as the size of the cluster increases. Thus, homeostatic
      events at the migratory front control community integrity, efficiency, and
      coordination, emphasizing the importance of interactions and cell counting in
      fine-tuning collective processes.

PMID- 21957237
TI  - Functional dissociation of hippocampal mechanism during implicit learning based
      on the domain of associations.
AB  - Traditionally, the medial temporal lobe (MTL) was linked to explicit or
      declarative memory in associative learning. However, recent studies have reported
      MTL involvement even when volunteers are not consciously aware of the learned
      contingencies. Therefore, the mechanism of the MTL-related learning process
      cannot be described sufficiently by the explicit/implicit distinction, and the
      underlying process in the MTL for associative learning needs a more functional
      characterization. A possible feature that would allow a functional specification
      also for implicit learning is the nature of the material that is learned. Given
      that implicit memory tasks often comprise a combination of perceptual and motor
      learning, we hypothesized that implicit learning of the perceptual but not the
      motor component entails MTL activation in these studies. To directly test this
      hypothesis, we designed a purely perceptual and a purely motor variant of the
      serial reaction time task. In two groups of human volunteers, behavioral results
      clearly showed that both variants were learned without awareness. Neuronal
      recordings using fMRI revealed that bilateral hippocampal activation was observed
      only for implicit learning of the perceptual sequence, not for the motor
      sequence. This dissociation clearly shows that the functional role of the
      hippocampus for learning is determined by the domain of the learned association
      and that the function of the medial temporal lobe system is the processing of
      contingencies between perceptual features regardless of the explicit or implicit
      nature of the ensuing memory.

PMID- 21957236
TI  - Vitamin D deficiency promotes skeletal muscle hypersensitivity and sensory
      hyperinnervation.
AB  - Musculoskeletal pain affects nearly half of all adults, most of whom are vitamin
      D deficient. Previous findings demonstrated that putative nociceptors ("pain
      sensing" nerves) express vitamin D receptors (VDRs), suggesting responsiveness to
      1,25-dihydroxyvitamin D. In the present study, rats receiving vitamin D-deficient
      diets for 2-4 weeks showed mechanical deep muscle hypersensitivity, but not
      cutaneous hypersensitivity. Muscle hypersensitivity was accompanied by balance
      deficits and occurred before onset of overt muscle or bone pathology.
      Hypersensitivity was not due to hypocalcemia and was actually accelerated by
      increased dietary calcium. Morphometry of skeletal muscle innervation showed
      increased numbers of presumptive nociceptor axons (peripherin-positive axons
      containing calcitonin gene-related peptide), without changes in sympathetic or
      skeletal muscle motor innervation. Similarly, there was no change in epidermal
      innervation. In culture, sensory neurons displayed enriched VDR expression in
      growth cones, and sprouting was regulated by VDR-mediated rapid response
      signaling pathways, while sympathetic outgrowth was not affected by different
      concentrations of 1,25-dihydroxyvitamin D. These findings indicate that vitamin D
      deficiency can lead to selective alterations in target innervation, resulting in
      presumptive nociceptor hyperinnervation of skeletal muscle, which in turn is
      likely to contribute to muscular hypersensitivity and pain.

PMID- 21957238
TI  - Homeodomain interacting protein kinase 2 regulates postnatal development of
      enteric dopaminergic neurons and glia via BMP signaling.
AB  - Trophic factor signaling is important for the migration, differentiation, and
      survival of enteric neurons during development. The mechanisms that regulate the
      maturation of enteric neurons in postnatal life, however, are poorly understood.
      Here, we show that transcriptional cofactor HIPK2 (homeodomain interacting
      protein kinase 2) is required for the maturation of enteric neurons and for
      regulating gliogenesis during postnatal development. Mice lacking HIPK2 display a
      spectrum of gastrointestinal (GI) phenotypes, including distention of colon and
      slowed GI transit time. Although loss of HIPK2 does not affect the enteric
      neurons in prenatal development, a progressive loss of enteric neurons occurs
      during postnatal life in Hipk2(-/-) mutant mice that preferentially affects the
      dopaminergic population of neurons in the caudal region of the intestine. The
      mechanism by which HIPK2 regulates postnatal enteric neuron development appears
      to involve the response of enteric neurons to bone morphogenetic proteins (BMPs).
      Specifically, compared to wild type mice, a larger proportion of enteric neurons
      in Hipk2(-/-) mutants have an abnormally high level of phosphorylated Smad1/5/8.
      Consistent with the ability of BMP signaling to promote gliogenesis, Hipk2(-/-)
      mutants show a significant increase in glia in the enteric nervous system. In
      addition, numbers of autophagosomes are increased in enteric neurons in Hipk2(-/
      ) mutants, and synaptic maturation is arrested. These results reveal a new role
      for HIPK2 as an important transcriptional cofactor that regulates the BMP
      signaling pathway in the maintenance of enteric neurons and glia, and further
      suggest that HIPK2 and its associated signaling mechanisms may be therapeutically
      altered to promote postnatal neuronal maturation.

PMID- 21957239
TI  - The plasma membrane-associated GTPase Rin interacts with the dopamine transporter
      and is required for protein kinase C-regulated dopamine transporter trafficking.
AB  - Dopaminergic signaling and plasticity are essential to numerous CNS functions and
      pathologies, including movement, cognition, and addiction. The amphetamine- and
      cocaine-sensitive dopamine (DA) transporter (DAT) tightly controls extracellular
      DA concentrations and half-life. DAT function and surface expression are not
      static but are dynamically modulated by membrane trafficking. We recently
      demonstrated that the DAT C terminus encodes a PKC-sensitive internalization
      signal that also suppresses basal DAT endocytosis. However, the cellular
      machinery governing regulated DAT trafficking is not well defined. In work
      presented here, we identified the Ras-like GTPase, Rin (for Ras-like in neurons)
      (Rit2), as a protein that interacts with the DAT C-terminal endocytic signal.
      Yeast two-hybrid, GST pull down and FRET studies establish that DAT and Rin
      directly interact, and colocalization studies reveal that DAT/Rin associations
      occur primarily in lipid raft microdomains. Coimmunoprecipitations demonstrate
      that PKC activation regulates Rin association with DAT. Perturbation of Rin
      function with GTPase mutants and shRNA-mediated Rin knockdown reveals that Rin is
      critical for PKC-mediated DAT internalization and functional downregulation.
      These results establish that Rin is a DAT-interacting protein that is required
      for PKC-regulated DAT trafficking. Moreover, this work suggests that Rin
      participates in regulated endocytosis.

PMID- 21957240
TI  - Scene-selective cortical regions in human and nonhuman primates.
AB  - fMRI studies have revealed three scene-selective regions in human visual cortex
      [the parahippocampal place area (PPA), transverse occipital sulcus (TOS), and
      retrosplenial cortex (RSC)], which have been linked to higher-order functions
      such as navigation, scene perception/recognition, and contextual association.
      Here, we document corresponding (presumptively homologous) scene-selective
      regions in the awake macaque monkey, based on direct comparison to human maps,
      using identical stimuli and largely overlapping fMRI procedures. In humans, our
      results showed that the three scene-selective regions are centered near-but
      distinct from-the gyri/sulci for which they were originally named. In addition,
      all these regions are located within or adjacent to known retinotopic areas.
      Human RSC and PPA are located adjacent to the peripheral representation of
      primary and secondary visual cortex, respectively. Human TOS is located
      immediately anterior/ventral to retinotopic area V3A, within retinotopic regions
      LO-1, V3B, and/or V7. Mirroring the arrangement of human regions fusiform face
      area (FFA) and PPA (which are adjacent to each other in cortex), the presumptive
      monkey homolog of human PPA is located adjacent to the monkey homolog of human
      FFA, near the posterior superior temporal sulcus. Monkey TOS includes the region
      predicted from the human maps (macaque V4d), extending into retinotopically
      defined V3A. A possible monkey homolog of human RSC lies in the medial bank, near
      peripheral V1. Overall, our findings suggest a homologous neural architecture for
      scene-selective regions in visual cortex of humans and nonhuman primates,
      analogous to the face-selective regions demonstrated earlier in these two
      species.

PMID- 21957241
TI  - Scale-free properties of the functional magnetic resonance imaging signal during
      rest and task.
AB  - It has been shown recently that a significant portion of brain electrical field
      potentials consists of scale-free dynamics. These scale-free brain dynamics
      contain complex spatiotemporal structures and are modulated by task performance.
      Here we show that the fMRI signal recorded from the human brain is also scale
      free; its power-law exponent differentiates between brain networks and correlates
      with fMRI signal variance and brain glucose metabolism. Importantly, in parallel
      to brain electrical field potentials, the variance and power-law exponent of the
      fMRI signal decrease during task activation, suggesting that the signal contains
      more long-range memory during rest and conversely is more efficient at online
      information processing during task. Remarkably, similar changes also occurred in
      task-deactivated brain regions, revealing the presence of an optimal dynamic
      range in the fMRI signal. The scale-free properties of the fMRI signal and brain
      electrical field potentials bespeak their respective stationarity and
      nonstationarity. This suggests that neurovascular coupling mechanism is likely to
      contain a transformation from nonstationarity to stationarity. In summary, our
      results demonstrate the functional relevance of scale-free properties of the fMRI
      signal and impose constraints on future models of neurovascular coupling.

PMID- 21957242
TI  - Modulation of Fgfr1a signaling in zebrafish reveals a genetic basis for the
      aggression-boldness syndrome.
AB  - Behavioral syndromes are suites of two or more behaviors that correlate across
      environmental contexts. The aggression-boldness syndrome links aggression,
      boldness, and exploratory activity in a novel environment. Although aggression
      boldness has been described in many animals, the mechanism linking its behavioral
      components is not known. Here we show that mutation of the gene encoding
      fibroblast growth factor receptor 1a (fgfr1a) simultaneously increases
      aggression, boldness, and exploration in adult zebrafish. We demonstrate that
      altered Fgf signaling also results in reduced brain histamine levels in mutants.
      Pharmacological increase of histamine signaling is sufficient to rescue the
      behavioral phenotype of fgfr1a mutants. Together, we show that a single genetic
      locus can underlie the aggression-boldness behavioral syndrome. We also identify
      one of the neurotransmitter pathways that may mediate clustering of these
      behaviors.

PMID- 21957243
TI  - Serotonin, via HTR2 receptors, excites neurons in a cortical-like premotor
      nucleus necessary for song learning and production.
AB  - Serotonin (5-HT) is a neuromodulator that is important for neural development,
      learning and memory, mood, and perception. Dysfunction of the serotonin system is
      central to depression and other clinically important mood disorders and has been
      linked with learning deficits. In mammals, 5-HT release from the raphe nuclei in
      the brainstem can modulate the functional properties of cortical neurons,
      influencing sensory and motor processing. Birds also have serotonergic neurons in
      the dorsal raphe, suggesting that 5-HT plays similar roles in sensory and motor
      processing, perhaps modulating brain circuitry underlying birdsong. To
      investigate this possibility, we measured the effects of 5-HT on spontaneous
      firing of projection neurons in the premotor robust nucleus of the arcopallium in
      brain slices from male zebra finches. These neurons are thought be akin to
      cortical layer V pyramidal neurons. 5-HT dramatically and reversibly enhanced the
      endogenous firing of RA neurons. Using pharmacological agonists and antagonists
      in vitro, we determined this action is mediated via HTR2 receptors, which we
      verified are expressed by in situ hybridization. Finally, focal administration of
      the serotonin selective reuptake inhibitor fluvoxamine revealed that endogenous 5
      HT is sufficient to mediate this effect in vivo. These findings reveal a
      modulatory action of serotonin on the physiology of the song system circuitry and
      suggest a novel role of serotonin in regulating song production and/or learning;
      further understanding of the role of 5-HT in this system may help illuminate the
      complex role of this neuromodulator in social interactions and motor plasticity
      in humans.

PMID- 21957245
TI  - Protection and expression of human motor memories.
AB  - When we adapt our movements to a perturbation, and then adapt to another
      perturbation, is the initial memory destroyed, or is it protected? Despite
      decades of experiments, this question remains unresolved. The confusion, in our
      view, is due to the fact that in every instance the approach has been to assay
      contents of motor memory by retesting with the same perturbations. When
      performance in retesting is the same as naive, this is usually interpreted as the
      memory being destroyed. However, it is also possible that the initial memory is
      simply masked by the competing memory. We trained humans in a reaching task in
      field B and then in field A (or washout) over an equal number of trials. To assay
      contents of motor memory, we used a new tool: after completion of training in A,
      we withheld reinforcement (i.e., reward) for a brief block of trials and then
      clamped movement errors to zero over a long block of trials. We found that this
      led to spontaneous recovery of B. That is, withholding reinforcement for the
      current motor output resulted in the expression of the competing memory.
      Therefore, adaptation followed by washout or reverse adaptation produced
      competing motor memories. The protection from unlearning was unrelated to sudden
      changes in performance errors that might signal a contextual change, as competing
      memories formed even when the perturbations were introduced gradually. Rather,
      reinforcement appears to be a critical signal that affords protection to motor
      memories, and lack of reinforcement encourages retrieval of a competing memory.

PMID- 21957244
TI  - Activation of postnatal neural stem cells requires nuclear receptor TLX.
AB  - Neural stem cells (NSCs) continually produce new neurons in postnatal brains.
      However, the majority of these cells stay in a nondividing, inactive state. The
      molecular mechanism that is required for these cells to enter proliferation still
      remains largely unknown. Here, we show that nuclear receptor TLX (NR2E1) controls
      the activation status of postnatal NSCs in mice. Lineage tracing indicates that
      TLX-expressing cells give rise to both activated and inactive postnatal NSCs.
      Surprisingly, loss of TLX function does not result in spontaneous glial
      differentiation, but rather leads to a precipitous age-dependent increase of
      inactive cells with marker expression and radial morphology for NSCs. These
      inactive cells are mispositioned throughout the granular cell layer of the
      dentate gyrus during development and can proliferate again after reintroduction
      of ectopic TLX. RNA-seq analysis of sorted NSCs revealed a TLX-dependent global
      expression signature, which includes the p53 signaling pathway. TLX regulates p21
      expression in a p53-dependent manner, and acute removal of p53 can rescue the
      proliferation defect of TLX-null NSCs in culture. Together, these findings
      suggest that TLX acts as an essential regulator that ensures the proliferative
      ability of postnatal NSCs by controlling their activation through genetic
      interaction with p53 and other signaling pathways.

PMID- 21957246
TI  - Spongiform encephalopathy in transgenic mice expressing a point mutation in the
      beta2-alpha2 loop of the prion protein.
AB  - Transmissible spongiform encephalopathies are fatal neurodegenerative diseases
      attributed to misfolding of the cellular prion protein, PrP(C), into a beta-sheet
      rich, aggregated isoform, PrP(Sc). We previously found that expression of mouse
      PrP with the two amino acid substitutions S170N and N174T, which result in high
      structural order of the beta2-alpha2 loop in the NMR structure at pH 4.5 and 20
      degrees C, caused transmissible de novo prion disease in transgenic mice. Here we
      report that expression of mouse PrP with the single-residue substitution D167S,
      which also results in a structurally well ordered beta2-alpha2 loop at 20 degrees
      C, elicits spontaneous PrP aggregation in vivo. Transgenic mice expressing
      PrP(D167S) developed a progressive encephalopathy characterized by abundant PrP
      plaque formation, spongiform change, and gliosis. These results add to the
      evidence that the beta2-alpha2 loop has an important role in intermolecular
      interactions, including that it may be a key determinant of prion protein
      aggregation.

PMID- 21957247
TI  - Systematic representation of sound locations in the primary auditory cortex.
AB  - The primary auditory cortex (A1) is involved in sound localization. A consistent
      observation in A1 is a clustered representation of binaural properties, but how
      spatial tuning varies within binaural clusters is unknown. Here, this issue was
      addressed in A1 of the pallid bat, a species that relies on passive hearing (as
      opposed to echolocation) to localize prey. Evidence is presented for systematic
      representations of sound azimuth within two binaural clusters in the pallid bat
      A1: the binaural inhibition (EI) and peaked (P) binaural interaction clusters.
      The representation is not a "point-to-point" space map as seen in the superior
      colliculus, but is in the form of a systematic increase in the area of activated
      cortex as azimuth changes from ipsilateral to contralateral locations. The
      underlying substrate in the EI cluster is a systematic representation of the
      medial boundary of azimuth receptive fields. The P cluster is activated mostly
      for sounds near the midline, providing a spatial acoustic fovea. Activity in the
      P cluster falls off systematically as the sound is moved to more lateral
      locations. Sensitivity to interaural intensity differences predicts azimuth
      tuning in the vast majority of neurons. Azimuth receptive field properties are
      relatively stable across intensity over a moderate range (20-40 dB above
      threshold) of intensities. This suggests that the maps will be similar across the
      intensities tested. These results challenge the current view that no systematic
      representation of azimuth is present in A1 and show that such representations are
      present locally within individual binaural clusters.

PMID- 21957248
TI  - Rapid dopamine signaling differentially modulates distinct microcircuits within
      the nucleus accumbens during sucrose-directed behavior.
AB  - The mesolimbic dopamine projection from the ventral tegmental area (VTA) to the
      nucleus accumbens (NAc) is critical in mediating reward-related behaviors, but
      the precise role of dopamine in this process remains unknown. We completed a
      series of studies to examine whether coincident changes occur in NAc cell firing
      and rapid dopamine release during goal-directed behaviors for sucrose and if so,
      to determine whether the two are causally linked. We show that distinct
      populations of NAc neurons differentially encode sucrose-directed behaviors, and
      using a combined electrophysiology/electrochemistry technique, further show that
      it is at those locations that rapid dopamine signaling is observed. To determine
      causality, NAc cell firing was recorded during selective pharmacological
      inactivation of dopamine burst firing using the NMDA receptor antagonist, AP-5.
      We show that phasic dopamine selectively modulates excitatory but not inhibitory
      responses of NAc neurons during sucrose-seeking behavior. Thus, rapid dopamine
      signaling does not exert global actions in the NAc but selectively modulates
      discrete NAc microcircuits that ultimately influence goal-directed actions.

PMID- 21957249
TI  - Single-channel and structural foundations of neuronal alpha7 acetylcholine
      receptor potentiation.
AB  - Potentiation of neuronal nicotinic acetylcholine receptors by exogenous ligands
      is a promising strategy for treatment of neurological disorders including
      Alzheimer's disease and schizophrenia. To gain insight into molecular mechanisms
      underlying potentiation, we examined ACh-induced single-channel currents through
      the human neuronal alpha7 acetylcholine receptor in the presence of the alpha7
      specific potentiator PNU-120596 (PNU). Compared to the unusually brief single
      channel opening episodes elicited by agonist alone, channel opening episodes in
      the presence of agonist and PNU are dramatically prolonged. Dwell time analysis
      reveals that PNU introduces two novel components into open time histograms,
      indicating at least two degrees of PNU-induced potentiation. Openings of the
      longest potentiated class coalesce into clusters whose frequency and duration
      change over a narrow range of PNU concentration. At PNU concentrations
      approaching saturation, these clusters last up to several minutes, prolonging the
      submillisecond alpha7 opening episodes by several orders of magnitude. Mutations
      known to reduce PNU potentiation at the whole-cell level still give rise to
      multisecond-long single-channel clusters. However mutation of five residues
      lining a cavity within each subunit's transmembrane domain abolishes PNU
      potentiation, defining minimal structural determinants of PNU potentiation.

PMID- 21957250
TI  - Dynamic activation of frontal, parietal, and sensory regions underlying
      anticipatory visual spatial attention.
AB  - Although it is well established that multiple frontal, parietal, and occipital
      regions in humans are involved in anticipatory deployment of visual spatial
      attention, less is known about the electrophysiological signals in each region
      across multiple subsecond periods of attentional deployment. We used MEG measures
      of cortical stimulus-locked, signal-averaged (event-related field) activity
      during a task in which a symbolic cue directed covert attention to the relevant
      location on each trial. Direction-specific attention effects occurred in
      different cortical regions for each of multiple time periods during the delay
      between the cue and imperative stimulus. A sequence of activation from V1/V2 to
      extrastriate, parietal, and frontal regions occurred within 110 ms after cue,
      possibly related to extraction of cue meaning. Direction-specific activations
      ~300 ms after cue in frontal eye field (FEF), lateral intraparietal area (LIP),
      and cuneus support early covert targeting of the cued location. This was followed
      by coactivation of a frontal-parietal system [superior frontal gyrus (SFG),
      middle frontal gyrus (MFG), LIP, anterior intraparietal sulcus (IPSa)] that may
      coordinate the transition from targeting the cued location to sustained
      deployment of attention to both space and feature in the last period. The last
      period involved direction-specific activity in parietal regions and both dorsal
      and ventral sensory regions [LIP, IPSa, ventral IPS, lateral occipital region,
      and fusiform gyrus], which was accompanied by activation that was not direction
      specific in right hemisphere frontal regions (FEF, SFG, MFG). Behavioral
      performance corresponded with the magnitude of attention-related activity in
      different brain regions at each time period during deployment. The results add to
      the emerging electrophysiological characterization of different cortical networks
      that operate during anticipatory deployment of visual spatial attention.

PMID- 21957251
TI  - Analgesic tolerance to high-efficacy agonists but not to morphine is diminished
      in phosphorylation-deficient S375A MU-opioid receptor knock-in mice.
AB  - Morphine is one of the most potent analgesic drugs. However, the utility of
      morphine in the management of chronic pain is limited by its rapid development of
      tolerance. Morphine exerts all of its pharmacological effects via the MU-opioid
      receptor. In many systems, tolerance is associated with phosphorylation and
      desensitization of G-protein-coupled receptors (GPCRs). In case of the MU-opioid
      receptor, phosphorylation occurs in an agonist-selective manner. High-efficacy
      agonists such as [d-Ala(2)-MePhe(4)-Gly-ol]enkephalin (DAMGO), fentanyl, or
      etonitazene stimulate the phosphorylation of both C-terminal threonine 370 (T370)
      and serine 375 (S375). In contrast, morphine promotes the phosphorylation of S375
      but fails to stimulate T370 phosphorylation. Here, we have assessed the
      contribution of S375 phosphorylation to the development of antinociceptive
      tolerance to high- and low-efficacy MU agonists in vivo. We show that S375
      phosphorylation of the MU-opioid receptor occurs in intact mouse brain in a dose
      dependent manner after administration of morphine, fentanyl, or etonitazene. In
      knock-in mice expressing the phosphorylation-deficient S375A mutant of the MU
      opioid receptor, morphine and fentanyl exhibited greater dose-dependent
      antinociceptive responses than in wild-type mice. However, acute and chronic
      tolerance to morphine was retained in S375A mutant mice. In contrast,
      antinociceptive tolerance after repeated subcutaneous application of etonitazene
      or repeated intracerebroventricular application of DAMGO was diminished. Thus,
      tolerance to MU agonists with different efficacies develops through distinct
      pathways. Whereas tolerance induced by DAMGO or etonitazene requires agonist
      driven phosphorylation of S375, the development and maintenance of
      antinociceptive tolerance to morphine occurs independent of S375 phosphorylation.

PMID- 21957252
TI  - The Drosophila SK channel (dSK) contributes to photoreceptor performance by
      mediating sensitivity control at the first visual network.
AB  - The contribution of the SK (small-conductance calcium-activated potassium)
      channel to neuronal functions in complex circuits underlying sensory processing
      and behavior is largely unknown in the absence of suitable animal models. Here,
      we generated a Drosophila line that lacks the single highly conserved SK gene in
      its genome (dSK). In R1-R6 photoreceptors, dSK encodes a slow Ca2+-activated K(+)
      current similar to its mammalian counterparts. Compared with wild-type, dSK(-)
      photoreceptors and interneurons showed accelerated oscillatory responses and
      adaptation. These enhanced kinetics were accompanied with more depolarized dSK(-)
      photoreceptors axons, assigning a role for dSK in network gain control during
      light-to-dark transitions. However, compensatory network adaptation, through
      increasing activity between synaptic neighbors, overcame many detriments of
      missing dSK current enabling dSK(-) photoreceptors to maintain normal information
      transfer rates to naturalistic stimuli. While demonstrating important functional
      roles for dSK channel in the visual circuitry, these results also clarify how
      homeostatically balanced network functions can compensate missing or faulty ion
      channels.

PMID- 21957253
TI  - Altered visual experience induces instructive changes of orientation preference
      in mouse visual cortex.
AB  - Stripe rearing, the restriction of visual experience to contours of only one
      orientation, leads to an overrepresentation of the experienced orientation among
      neurons in the visual cortex. It is unclear, however, how these changes are
      brought about. Are they caused by silencing of neurons tuned to non-experienced
      orientations, or do some neurons change their preferred orientation? To address
      this question, we stripe-reared juvenile mice using cylinder lens goggles.
      Following stripe rearing, the orientation preference of cortical neurons was
      determined with two-photon calcium imaging. This allowed us to sample all neurons
      in a given field of view, including the non-responsive ones, thus overcoming a
      fundamental limitation of extracellular electrophysiological recordings. Stripe
      rearing for 3 weeks resulted in a clear overrepresentation of the experienced
      orientation in cortical layer 2/3. Closer inspection revealed that the stripe
      rearing effect changed with depth in cortex: The fraction of responsive neurons
      decreased in upper layer 2/3, but changed very little deeper in this layer. At
      the same time, the overrepresentation of the experienced orientation was
      strongest in lower layer 2/3. Thus, diverse mechanisms contribute to the overall
      stripe rearing effect, but for neurons in lower layer 2/3 the effect is mediated
      by an instructive mechanism, which alters the orientation tuning of individual
      neurons.

PMID- 21957255
TI  - Short bouts of vocalization induce long-lasting fast gamma oscillations in a
      sensorimotor nucleus.
AB  - Performance evaluation is a critical feature of motor learning. In the vocal
      system, it requires the integration of auditory feedback signals with vocal motor
      commands. The network activity that supports such integration is unknown, but it
      has been proposed that vocal performance evaluation occurs offline. Recording
      from NIf, a sensorimotor structure in the avian song system, we show that short
      bouts of singing in adult male zebra finches (Taeniopygia guttata) induce
      persistent increases in firing activity and coherent oscillations in the fast
      gamma range (90-150 Hz). Single units are strongly phase locked to these
      oscillations, which can last up to 30 s, often outlasting vocal activity by an
      order of magnitude. In other systems, oscillations often are triggered by events
      or behavioral tasks but rarely outlast the event that triggered them by more than
      1 s. The present observations are the longest reported gamma oscillations
      triggered by an isolated behavioral event. In mammals, gamma oscillations have
      been associated with memory consolidation and are hypothesized to facilitate
      communication between brain regions. We suggest that the timing and persistent
      nature of NIf's fast gamma oscillations make them well suited to facilitate the
      integration of auditory and vocal motor traces associated with vocal performance
      evaluation.

PMID- 21957254
TI  - SRY-box containing gene 17 regulates the Wnt/beta-catenin signaling pathway in
      oligodendrocyte progenitor cells.
AB  - The SRY-box (Sox) transcription factors regulate oligodendrocyte differentiation,
      but their signaling targets are largely unknown. We have identified a major
      signal transduction pathway regulated by Sox containing gene 17 (Sox17) in the
      oligodendrocyte lineage. Microarray analysis in oligodendrocyte progenitor cells
      (OPCs) after Sox17 attenuation revealed upregulated genes associated with cell
      cycle control and activation of the Wingless and integration site (Wnt)/beta
      catenin pathway. Sox17 knockdown also increases the levels of cyclin D1, Axin2,
      and activated beta-catenin. In OPCs, the expression pattern of Sox17, cyclin D1,
      and secreted Frizzled-related protein-1 in the presence of platelet-derived
      growth factor (PDGF) was coordinately accelerated by addition of thyroid hormone,
      indicating differentiation-induced regulation of Sox17 targets. In developing
      white matter, decreased total beta-catenin, activated beta-catenin, and cyclin D1
      levels coincided with the peak of Sox17 expression, and immunoprecipitates showed
      a developmentally regulated interaction among Sox17, T-cell transcription factor
      4, and beta-catenin proteins. In OPCs, PDGF stimulated phosphorylation of
      glycogen synthase 3beta and the Wnt coreceptor LRP6, and enhanced beta-catenin
      dependent gene expression. Sox17 overexpression inhibited PDGF-induced TOPFLASH
      and cyclin D1 promoter activity, and decreased endogenous cyclin D1, activated
      beta-catenin, as well as total beta-catenin levels. Recombinant Sox17 prevented
      Wnt3a from repressing myelin protein expression, and inhibition of Sox17-mediated
      proteasomal degradation of beta-catenin blocked myelin protein induction. These
      results indicate that Sox17 suppresses cyclin D1 expression and cell
      proliferation by directly antagonizing beta-catenin, whose activity in OPCs is
      stimulated not only by Wnt3a, but also by PDGF. Our identification of downstream
      targets of Sox17 thus defines signaling pathways and molecular mechanisms in OPCs
      that are regulated by Sox17 during cell cycle exit and the onset of
      differentiation in oligodendrocyte development.

PMID- 21957256
TI  - Multisensory calibration is independent of cue reliability.
AB  - Multisensory calibration is fundamental for proficient interaction within a
      changing environment. Initial studies suggested a visual-dominant mechanism. More
      recently, a cue-reliability-based model, similar to optimal cue integration, has
      been proposed. However, a more general, reliability-independent model of fixed
      ratio adaptation (of which visual dominance is a subcase) has never been tested.
      Here, we studied behavior of both humans and monkeys performing a heading
      discrimination task. Subjects were presented with either visual (optic-flow),
      vestibular (motion-platform), or combined (visual-vestibular) stimuli and
      required to report whether self-motion was to the right/left of straight ahead. A
      systematic heading discrepancy was introduced between the visual and vestibular
      cues, without external feedback. Cue calibration was measured by the resulting
      sensory adaptation. Both visual and vestibular cues significantly adapted in the
      direction required to reduce cue conflict. However, unlike multisensory cue
      integration, cue calibration was not reliability based. Rather, a model of fixed
      ratio adaptation best described the data, whereby vestibular adaptation was
      greater than visual adaptation, regardless of relative cue reliability. The
      average ratio of vestibular to visual adaptation was 1.75 and 2.30 for the human
      and monkey data, respectively. Furthermore, only through modeling fixed-ratio
      adaptation (using the ratio extracted from the data) were we able to account for
      reliability-based cue integration during the adaptation process. The finding that
      cue calibration does not depend on cue reliability is consistent with the notion
      that it follows an underlying estimate of cue accuracy. Cue accuracy is generally
      independent of cue reliability, and its estimate may change with a much slower
      time constant. Thus, greater vestibular versus visual (fixed-ratio) adaptation
      suggests lower vestibular versus visual cue accuracy.

PMID- 21957258
TI  - Regulation of synaptic vesicle budding and dynamin function by an EHD ATPase.
AB  - Eps15 homology domain-containing proteins (EHDs) are conserved ATPases implicated
      in membrane remodeling. Recently, EHD1 was found to be enriched at synaptic
      release sites, suggesting a possible involvement in the trafficking of synaptic
      vesicles. We have investigated the role of an EHD1/3 ortholog (l-EHD) in the
      lamprey giant reticulospinal synapse. l-EHD was detected by immunogold at
      endocytic structures adjacent to release sites. In antibody microinjection
      experiments, perturbation of l-EHD inhibited synaptic vesicle endocytosis and
      caused accumulation of clathrin-coated pits with atypical, elongated necks. The
      necks were covered with helix-like material containing dynamin. To test whether l
      EHD directly interferes with dynamin function, we used fluid-supported bilayers
      as in vitro assay. We found that l-EHD strongly inhibited vesicle budding induced
      by dynamin in the constant presence of GTP. l-EHD also inhibited dynamin-induced
      membrane tubulation in the presence of GTPgammaS, a phenomenon linked with
      dynamin helix assembly. Our in vivo results demonstrate the involvement of l-EHD
      in clathrin/dynamin-dependent synaptic vesicle budding. Based on our in vitro
      observations, we suggest that l-EHD acts to limit the formation of long,
      unproductive dynamin helices, thereby promoting vesicle budding.

PMID- 21957257
TI  - Neural correlates of interindividual differences in children's audiovisual speech
      perception.
AB  - Children use information from both the auditory and visual modalities to aid in
      understanding speech. A dramatic illustration of this multisensory integration is
      the McGurk effect, an illusion in which an auditory syllable is perceived
      differently when it is paired with an incongruent mouth movement. However, there
      are significant interindividual differences in McGurk perception: some children
      never perceive the illusion, while others always do. Because converging evidence
      suggests that the posterior superior temporal sulcus (STS) is a critical site for
      multisensory integration, we hypothesized that activity within the STS would
      predict susceptibility to the McGurk effect. To test this idea, we used BOLD fMRI
      in 17 children aged 6-12 years to measure brain responses to the following three
      audiovisual stimulus categories: McGurk incongruent, non-McGurk incongruent, and
      congruent syllables. Two separate analysis approaches, one using independent
      functional localizers and another using whole-brain voxel-based regression,
      showed differences in the left STS between perceivers and nonperceivers. The STS
      of McGurk perceivers responded significantly more than that of nonperceivers to
      McGurk syllables, but not to other stimuli, and perceivers' hemodynamic responses
      in the STS were significantly prolonged. In addition to the STS, weaker
      differences between perceivers and nonperceivers were observed in the fusiform
      face area and extrastriate visual cortex. These results suggest that the STS is
      an important source of interindividual variability in children's audiovisual
      speech perception.

PMID- 21957259
TI  - The cortical rhythms of chronic back pain.
AB  - Chronic pain is maladaptive and influences brain function and behavior by
      altering the flow and integration of information across brain regions. Here we
      use a power spectral analysis to investigate impact of presence of chronic pain
      on brain oscillatory activity in humans. We examine changes in BOLD fluctuations,
      across different frequencies, in chronic back pain (CBP) patients (n = 15) as
      compared to healthy controls (n = 15) during resting-state fMRI. While healthy
      subjects exhibited a specific, frequency band-dependent, large-scale neural
      organization, patients showed increased high-frequency BOLD oscillations (0.12
      0.20 Hz) circumscribed mainly to medial prefrontal cortex (mPFC) and parts of the
      default mode network. In the patients a correlation analysis related the mPFC
      aberrant BOLD high-frequency dynamics to altered functional connectivity to pain
      signaling/modulating brain regions, thus linking BOLD frequency changes to
      function. We also found that increased frequency fluctuations within the mPFC
      were temporally synchronous with spontaneous pain changes in patients during a
      pain-rating task. These observations provide novel insights about the nature of
      CBP, identifying how it disturbs the resting brain, and link high-frequency BOLD
      oscillations to perception.

PMID- 21957260
TI  - Peptide neuromodulation of synaptic dynamics in an oscillatory network.
AB  - Although neuromodulation of synapses is extensively documented, its consequences
      in the context of network oscillations are not well known. We examine the
      modulation of synaptic strength and short-term dynamics in the crab pyloric
      network by the neuropeptide proctolin. Pyloric oscillations are driven by a
      pacemaker group which receives feedback through the inhibitory synapse from the
      lateral pyloric (LP) to pyloric dilator (PD) neurons. We show that proctolin
      modulates the spike-mediated and graded components of the LP to PD synapse.
      Proctolin enhances the graded component and unmasks a surprising heterogeneity in
      its dynamics where there is depression or facilitation depending on the amplitude
      of the voltage waveform of the presynaptic LP neuron. The spike-mediated
      component is influenced by the baseline membrane potential and is also enhanced
      by proctolin at all baseline potentials. In addition to direct modulation of this
      synapse, proctolin also changes the shape and amplitude of the presynaptic
      voltage waveform which additionally enhances synaptic output during ongoing
      activity. During ongoing oscillations, proctolin reduces the variability of cycle
      period but only when the LP to PD synapse is functionally intact. Using the
      dynamic clamp technique we find that the reduction in variability is a direct
      consequence of modulation of the LP to PD synapse. These results demonstrate that
      neuromodulation of synapses involves complex and interacting influences that
      target different synaptic components and dynamics as well as the presynaptic
      voltage waveform. At the network level, modulation of feedback inhibition can
      result in reduction of variability and enhancement of stable oscillatory output.

PMID- 21957261
TI  - A nine amino acid domain is essential for mutant prion protein toxicity.
AB  - Transgenic mice expressing prion protein (PrP) molecules with several different
      internal deletions display spontaneous neurodegenerative phenotypes that can be
      dose-dependently suppressed by coexpression of wild-type PrP. Each of these
      deletions, including the largest one (Delta32-134), retains 9 aa immediately
      following the signal peptide cleavage site (residues 23-31; KKRPKPGGW). These
      residues have been implicated in several biological functions of PrP, including
      endocytic trafficking and binding of glycosaminoglycans. We report here on our
      experiments to test the role of this domain in the toxicity of deleted forms of
      PrP. We find that transgenic mice expressing Delta23-134 PrP display no clinical
      symptoms or neuropathology, in contrast to mice expressing Delta32-134 PrP,
      suggesting that residues 23-31 are essential for the toxic phenotype. Using a
      newly developed cell culture assay, we narrow the essential region to amino acids
      23-26, and we show that mutant PrP toxicity is not related to the role of the N
      terminal residues in endocytosis or binding to endogenous glycosaminoglycans.
      However, we find that mutant PrP toxicity is potently inhibited by application of
      exogenous glycosaminoglycans, suggesting that the latter molecules block an
      essential interaction between the N terminus of PrP and a membrane-associated
      target site. Our results demonstrate that a short segment containing positively
      charged amino acids at the N terminus of PrP plays an essential role in mediating
      PrP-related neurotoxicity. This finding identifies a protein domain that may
      serve as a drug target for amelioration of prion neurotoxicity.

PMID- 21957262
TI  - Draxin inhibits axonal outgrowth through the netrin receptor DCC.
AB  - Draxin, a recently identified axon guidance protein, is essential for the
      formation of forebrain commissures, and can mediate repulsion of netrin
      stimulated spinal commissural axons. Here, we report that draxin binds multiple
      netrin receptors: DCC (deleted in colorectal cancer), Neogenin, UNC5s (H1, H2,
      H3), and DSCAM (Down's syndrome cell adhesion molecule). Since draxin and Dcc
      knockouts showed similar phenotype in forebrain commissures formation, we show
      here the functional importance of draxin/DCC interaction. Draxin interacts with
      subnanomolar affinity to the netrin receptor DCC, in a region of DCC distinct
      from its netrin-binding domain. In vitro, neurite outgrowth from cortical and
      olfactory bulb explants of Dcc knock-out mice is significantly less inhibited by
      draxin, when compared with neurites from explants of wild-type mice. Furthermore,
      in comparison with wild-type mice, the growth cone collapse in response to draxin
      is largely abolished in Dcc-deficient cortical neurons. In vivo, double heteros
      of draxin/Dcc mice show markedly higher frequency of complete agenesis of corpus
      callosum than either of the single hetero. These results identify DCC as a
      convergent receptor for netrin and draxin in axon growth and guidance.

PMID- 21957263
TI  - Functional plasticity of central TRPV1 receptors in brainstem dorsal vagal
      complex circuits of streptozotocin-treated hyperglycemic mice.
AB  - Emerging data indicate that central neurons participate in diabetic processes by
      modulating autonomic output from neurons in the dorsal motor nucleus of the vagus
      (DMV). We tested the hypothesis that synaptic modulation by transient receptor
      potential vanilloid type 1 (TRPV1) receptors is reduced in the DMV in slices from
      a murine model of type 1 diabetes. The TRPV1 agonist capsaicin robustly enhanced
      glutamate release onto DMV neurons by acting at preterminal receptors in slices
      from intact mice, but failed to do so in slices from diabetic mice. TRPV1
      receptor protein expression in the vagal complex was unaltered. Brief insulin
      preapplication restored TRPV1-dependent modulation of glutamate release in a PKC-
      and PI3K-dependent manner. The restorative effect of insulin was prevented by
      brefeldin A, suggesting that insulin induced TRPV1 receptor trafficking to the
      terminal membrane. Central vagal circuits critical to the autonomic regulation of
      metabolism undergo insulin-dependent synaptic plasticity involving TRPV1 receptor
      modulation in diabetic mice after several days of chronic hyperglycemia.

PMID- 21957264
TI  - Synaptophysin is required for synaptobrevin retrieval during synaptic vesicle
      endocytosis.
AB  - The integral synaptic vesicle (SV) protein synaptophysin forms ~10% of total SV
      protein content, but has no known function in SV physiology. Synaptobrevin
      (sybII) is another abundant integral SV protein with an essential role in SV
      exocytosis. Synaptophysin and sybII form a complex in nerve terminals, suggesting
      this interaction may have a key role in presynaptic function. To determine how
      synaptophysin controls sybII traffic in nerve terminals, we used a combination of
      optical imaging techniques in cultures derived from synaptophysin knock-out mice.
      We show that synaptophysin is specifically required for the retrieval of the pH
      sensitive fluorescent reporter sybII-pHluorin from the plasma membrane during
      endocytosis. The retrieval of other SV protein cargo reporters still occurred;
      however, their recapture proceeded with slower kinetics. This slowing of SV
      retrieval kinetics in the absence of synaptophysin did not impact on global SV
      turnover. These results identify a specific and selective requirement for
      synaptophysin in the retrieval of sybII during SV endocytosis and suggest that
      their interaction may act as an adjustable regulator of SV retrieval efficiency.

PMID- 21957266
TI  - Retraction for Guo et al., Lmx1b-controlled isthmic organizer is essential for
      development of midbrain dopaminergic neurons.

PMID- 21957267
TI  - Hemokinin-1 stimulates prostaglandin E2 production in human colon through
      activation of cyclooxygenase-2 and inhibition of 15-hydroxyprostaglandin
      dehydrogenase.
AB  - Hemokinin-1 (HK-1) is a newly identified tachykinin, originating from the immune
      system rather than neurons, and may participate in the immune and inflammatory
      response. In colonic mucosa of patients with inflammatory bowel disease (IBD), up
      regulation of the TAC4 gene encoding HK-1 and increased production of
      prostaglandin E2 (PGE2) occur. Our aim was to examine the mechanistic link
      between human HK-1 and PGE2 production in normal human colon. Exogenous HK-1 (0.1
      MUM) for 4 h evoked an increased PGE2 release from colonic mucosal and muscle
      explants by 10- and 3.5-fold, respectively, compared with unstimulated time
      controls. The HK-1-stimulated PGE2 release was inhibited by the tachykinin
      receptor antagonists (S)1-2-[3-(3,4-dichlorophenyl)-1-(3
      isopropoxyphenylacetyl)piperidin-3-yl]ethyl-4-phenyl-l azonia
      bicyclo[2.2.2]octane (SR140333) [neurokinin-1 (NK1)] and N-[(2S)-4-(4-acetamido-4
      phenylpiperidin-1-yl)-2-(3,4-dichlorophenyl)butyl]-N-methylbenzamide (SR48968)
      [neurokinin-2 (NK2)] and was also inhibited by the cyclooxygenase (COX)-2
      inhibitor N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide) (NS-398) but not
      by the COX-1 inhibitor 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3
      trifluoromethylpyrazole (SC-560). A parallel study with substance P showed
      similar results. Molecular studies with HK-1-treated explants demonstrated a
      stimulatory effect on COX-2 expression at both transcription and protein levels.
      It is noteworthy that this was coupled with HK-1-induced down-regulation of 15
      hydroxyprostaglandin dehydrogenase (15-PGDH) mRNA and protein expression.
      Immunoreactivity for 15-PGDH occurred on inflammatory cells, epithelial cells,
      platelets, and ganglia. This finding provides an additional mechanism for HK-1
      evoked PGE2 increase, in which HK-1 may interfere with the downstream metabolism
      of PGE2 by suppressing 15-PGDH expression. In conclusion, our results uncover a
      novel inflammatory role for HK-1, which signals via NK1 and NK2 receptors to
      regulate PGE2 release from human colonic tissue, and may further explain a
      pathological role for HK-1 in IBD when abnormal levels of PGE2 occur.

PMID- 21957265
TI  - Vagal afferent stimulation activates astrocytes in the nucleus of the solitary
      tract via AMPA receptors: evidence of an atypical neural-glial interaction in the
      brainstem.
AB  - The nucleus of the solitary tract (NST), located in the dorsomedial medulla, is
      the site of visceral sensory modulation of a variety of homeostatic reflexes.
      Given recent advancements in the understanding of active regulation of synaptic
      information flow by astrocytes, we sought to determine whether afferent sensory
      inputs to NST neurons also activates NST astrocytes. Using confocal, live-cell
      calcium imaging of brainstem slices, we investigated the possibility that
      stimulation of vagal sensory afferents, the major sensory input into the NST,
      activated NST astrocytes, as indicated by increases in astrocytic intracellular
      calcium concentrations ([Ca2+](i)). Astrocytes and neurons were preloaded with
      the calcium reporter dye Calcium Green, and astrocytes were selectively stained
      by sulforhodamine 101. Electrical stimulation of vagal afferent axons produced
      rapid increases in [Ca2+](i) in NST astrocytes as well as neurons. Surprisingly,
      this effect on astrocytes was blocked by the AMPA receptor antagonist NBQX and
      was unaffected by antagonism of NMDA and metabotropic glutamate receptors. Bath
      application of AMPA also activated astrocytes. This activation was dependent on
      extracellular Ca2+ influx through both typical AMPA receptors and calcium
      permeable AMPA receptors. This AMPA-mediated Ca2+ influx was further amplified by
      actions of the ryanodine receptor by way of calcium-induced calcium release. Our
      immunohistochemical staining of NST cells further verified the presence of the
      AMPAR subunit GluR1 on astrocytes. These observations suggest that NST astrocytes
      may be active participants in the regulation of autonomic reflexes even in the
      normal, healthy state.

PMID- 21957268
TI  - Development of a novel rating system to assess lower-limb comfort.
AB  - BACKGROUND: Comfort evaluation techniques are commonplace in medicine. However,
      measures of lower-limb comfort are infrequently used in the sporting environment.
      The purpose of this study was to develop an instrument for measuring lower-limb
      comfort, which will extend previous work in the field of injury awareness.
      METHODS: A lower-limb comfort index (LLCI) was developed for use in the
      environment of elite sport. Forty professional footballers participated in
      development of the index. The study had three components. A critical appraisal of
      the literature established the need for an LLCI. The second phase involved 20
      professional footballers establishing and testing the components of the comfort
      index as an instrument for measuring comfort. RESULTS: Nonparametric statistics
      (the McNemar test) in phase 2 indicated that the LLCI demonstrated good
      responsiveness to suitability (P = .019) and ease of use (P < .01). After a high
      level of agreement for responses, the third stage required 20 players to pilot
      test the reliability of the LLCI in a controlled environment. Repeated measures
      of difference between two periods for sum comfort (intraclass correlation
      coefficient = 0.99) and individual anatomical segments (kappa = 0.72-1) provided
      confidence that the comfort index was reliable. CONCLUSIONS: The LLCI showed good
      trait construct to provide confidence to conduct a future study to investigate
      interrater consistency in a wider cohort of professional footballers under
      different conditions, such as match-day and training-week environments.

PMID- 21957269
TI  - The correlation between plantar fascia thickness and symptoms of plantar
      fasciitis.
AB  - BACKGROUND: The purpose of this study was to determine whether changes in plantar
      fascia thickness are a reliable gauge of efficacy of treatment protocols for
      plantar fasciitis. METHODS: Thirty-nine feet (30 patients) with plantar fasciitis
      received an ultrasound examination to measure the thickness of the medial band of
      the plantar fascia. Each patient assessed his or her pain using the visual
      analogue scale. Following various treatments, a second ultrasound examination was
      performed and the thickness of the plantar fascia was again measured and
      subjective pain level assessed. RESULTS: Twenty-nine feet (74.4%) showed a
      decrease in plantar fascia thickness and a decrease in pain. One foot (2.6%)
      experienced an increase in fascia thickness and reported an increase in pain.
      Four feet (10.3%) had an increase in thickness of the plantar fascia and reported
      no change in pain level. Three feet had minor increases in fascia thickness but
      reported a decrease in pain (7.7%). One foot (2.6%) had no change in fascia
      thickness but a decrease in pain and one foot (2.6%) had a decrease in the
      plantar fascia but no change in pain level. The average reduction in fascia
      thickness was 0.82 mm +/- 1.04 mm, correlating with an average improvement in
      pain of 3.64 +/- 2.7 (P < 0.005). CONCLUSIONS: This study provides evidence that
      changing thickness of the plantar fascia is a valid objective measurement to
      assess effectiveness of new or existing treatment protocols.

PMID- 21957270
TI  - Stabilization of joint forces of the subtalar complex via HyProCure sinus tarsi
      stent.
AB  - BACKGROUND: The foot is the foundation of the body. The stability of the osseous
      hindfoot structure is crucial in bipedal locomotion. The subtalar joint is
      responsible for conversion of the rotatory forces of the lower extremities and
      dictates the movements of the midtarsal joints and the forefoot. In a
      hyperpronated foot, excessive abnormal pronation results in partial to full
      obliteration of the sinus tarsi. The hypothesis is that the HyProCure device will
      prevent obliteration of the sinus tarsi, thereby stabilizing the subtalar joint
      complex and eliminating the excessive forces to the proximal and distal
      musculoskeletal system that occur with every step. METHODS: Five fresh-frozen
      human foot cadaver specimens that represented pathologic hindfoot and midfoot
      instability and partial to full obliteration of the sinus tarsi were axially
      compressed to 2,000 N and internally rotated by 15 degrees  to produce maximum
      pronation of the subtalar joint using a biaxial materials testing machine. The
      forces were measured across the posterior and anterior talocalcaneal joint facets
      before and after placement of the HyProCure stent. RESULTS: The subtalar joint
      stabilized after placement of the HyProCure sinus tarsi stent. The mean +/- 1 SD
      forces in the posterior talocalcaneal joint increased from 795.88 +/- 106 N to
      1,004.86 +/- 72.41 N (P < 0.05, two-tailed paired t test). The mean +/- SD forces
      at the anterior talocalcaneal joint decreased from 520.15 +/- 127.18 N to 394.56
      +/- 73.83 N (P < 0.05), shifting the contact area posteriorly. CONCLUSIONS:
      Placement of the HyProCure subtalar stabilization stent in a hyperpronated foot
      prevents excessive talar subluxation and assists in proper distribution of the
      axial loads on the subtalar facet joints.

PMID- 21957271
TI  - The in vitro reliability of the CODA MPX30 as the basis for a method of assessing
      the in vivo motion of the subtalar joint.
AB  - BACKGROUND: The considerable variation in subtalar joint structure and function
      shown by studies indicates the importance of developing a noninvasive in vivo
      technique for assessing subtalar joint movement. This article reports the in
      vitro testing of the CODA MPX30, an active infrared marker motion analysis
      system. This work represents the first stage in the development of a noninvasive
      in vivo method for measuring subtalar joint motion during walking. METHODS: The
      in vitro repeatability of the CODA MPX30 system's measurements of marker
      position, simple and intermarker set angles, was tested. Angular orientations of
      markers representing the position of the talus and the calcaneus were measured
      using a purpose-designed marker placement model. RESULTS: Marker location
      measurements were shown to vary by less than 1.0 mm in all of the planes. The
      measurement of a 90 degrees  angle was also found to be repeatable in all of the
      planes, although measurements made in the yz plane were shown to be consistently
      inaccurate (mean, 92.47 degrees ). Estimation of segmental orientation was found
      to be repeatable. Estimations of marker set orientations were shown to increase
      in variability after a coordinate transform was performed (maximum SD, 1.14
      degrees ). CONCLUSIONS: The CODA MPX30 was shown to produce repeatable
      estimations of marker position. Levels of variation in segmental orientation
      estimates were shown to increase subsequent to coordinate transforms. The
      combination of the CODA MPX30 and an appropriate marker placement model offers
      the basis of an in vivo measurement strategy of subtalar joint movement, an
      important development in the understanding of the function of the joint during
      gait.

PMID- 21957272
TI  - Interrater and intrarater reliability in the measurement of ankle joint
      dorsiflexion is independent of examiner experience and technique used.
AB  - BACKGROUND: Goniometric measurement is currently being used as a diagnostic and
      outcomes assessment tool for ankle joint dorsiflexion. Despite its common use,
      its interrater and intrarater reliability has been questioned. METHODS: This is a
      prospective study examining whether the experience of the examiner or the
      technique used affects the interrater and intrarater reliability for measuring
      ankle joint dorsiflexion. Fourteen asymptomatic individuals (8 male and 6 female)
      with a mean age of 28.2 years (range, 23-52) were enrolled into this study. The
      years of clinical experience of the five examiners averaged 10.4 years (range, 0
      26). Four examiners used a modified Root, Weed and Orien method of measuring
      ankle joint dorsiflexion. The fifth examiner utilized a nonstandardized
      technique. A standard goniometer was used for bilateral measurements of ankle
      joint dorsiflexion with the knee extended and flexed. All five examiners repeated
      each measurement three times during each of the three sessions, with each session
      spaced at least 1 week apart. RESULTS: The interclass correlation coefficient
      reveals a moderate intrarater and poor interrater reliability in ankle joint
      dorsiflexion measurements using a standard goniometer. More importantly, further
      analysis indicates that the use of a standardized technique for measurement of
      ankle joint dorsiflexion or years of clinical experience does not increase the
      intrarater or interrater reliability. CONCLUSIONS: The utility of the goniometric
      measurement of ankle joint dorsiflexion may be limited.

PMID- 21957273
TI  - Changes in the plantar pressure distribution during gait throughout gestation.
AB  - BACKGROUND: The intention of this investigation was to longitudinally describe
      and compare the plantar pressure distribution in orthostatic posture and gait
      throughout pregnancy. METHODS: A prospective longitudinal observational study was
      conducted with six pregnant women (mean +/- SD age, 32 +/- 3 years) with a mean
      +/- SD weight gain of 10.0 +/- 1.4 kg. Peak pressure, contact time, contact area,
      and maximum force in five plantar areas were evaluated using capacitive insoles
      during gait and orthostatic posture. For 1 year, the plantar pressures of
      pregnant women were evaluated the last month of each trimester. Comparisons among
      plantar areas and trimesters were made by analysis of variance. RESULTS: For
      orthostatic posture, no differences in contact time, contact area, peak pressure,
      and maximum force throughout the trimesters were found. During gait, peak
      pressure and maximum force of the medial rearfoot were reduced from the first to
      third and second to third trimesters. Maximum force increased at the medial
      forefoot from the first to second trimester. Contact area increased at the
      lateral rearfoot from the second to third trimester and at the midfoot from the
      first to third trimester. Contact time increased at the midfoot and medial and
      lateral forefoot from the first to third trimester. CONCLUSIONS: Pregnant women
      do not alter plantar pressure during orthostatic posture, but, during gait, the
      plantar loads were redistributed from the rearfoot (decrease) to the midfoot and
      forefoot (increase) throughout pregnancy. These adjustments help maintain the
      dynamic stability of the pregnant woman during locomotion.

PMID- 21957274
TI  - Evaluating intratester reliability of manual masking of plantar pressure
      measurements associated with chronic gout.
AB  - BACKGROUND: Plantar pressure measurements are commonly used to evaluate foot
      function in chronic musculoskeletal conditions. However, manually identifying
      anatomical landmarks is a source of measurement error and can produce unreliable
      data. The aim of this study was to evaluate intratester reliability associated
      with manual masking of plantar pressure measurements in patients with gout.
      METHODS: Twenty-five patients with chronic gout (mean disease duration, 22 years)
      were recruited from rheumatology outpatient clinics. Patients were excluded if
      they were experiencing an acute gout flare at the time of assessment, had lower
      limb amputation, or had diabetes mellitus. Manual masking of peak plantar
      pressures and pressure-time integrals under ten regions of the foot were
      undertaken on two occasions on the same day using an in-shoe pressure measurement
      system. Test-retest reliability was assessed by using intraclass correlation
      coefficients, SEM, 95% limits of agreement, and minimal detectable change.
      RESULTS: Mean peak pressure intraclass correlation coefficients ranged from 0.92
      to 0.97, with SEM of 8% to 14%. The 95% limits of agreement ranged from-150.3 to
      133.5 kPa, and the minimal detectable change ranged from 30.8 to 80.6 kPa. For
      pressure-time integrals, intraclass correlation coefficients were 0.86 to 0.94,
      and SEM were 5% to 29%, with the greater errors observed under the toes. The 95%
      limits of agreement ranged from -48.5 to 48.8 kPa/sec, and the minimal detectable
      change ranged from 6.8 to 21.0 kPa/sec. CONCLUSIONS: These findings provide
      clinicians with information confirming the errors associated with manual masking
      of plantar pressure measurements in patients with gout.

PMID- 21957275
TI  - Relationship between the size of bone marrow edema of the talus and ankle pain.
AB  - BACKGROUND: We sought to determine the changes in the size of the edema observed
      on MRI scans and its relation to the patient's pain during activity and pain
      during rest in bone marrow edema. METHODS: A total of 26 patients were followed
      up at 3-month intervals for a period of 1 year. During the follow-ups, magnetic
      resonance imaging scans of the patients' ankles were obtained; the scores
      obtained on the American Orthopaedic Foot and Ankle Society functional rating
      scale and visual analog scale were determined. The changes in these parameters
      and the correlation between them were examined. RESULTS: The size of the edema as
      observed on magnetic resonance imaging scans decreased, and the pain during
      activity and rest decreased. Although there is a correlation between the decrease
      in the edema size observed on magnetic resonance imaging scans and decrease in
      the pain during activity, there is no correlation between the decrease in the
      edema size observed on magnetic resonance imaging scans and the decrease in pain
      during rest. CONCLUSIONS: Patients can be informed more precisely, that the pain
      during rest and activity may not decrease after the third and sixth month,
      respectively. Magnetic resonance imaging may not alter after the ninth month, so
      it may not be necessary to be performed again.

PMID- 21957276
TI  - The Charcot foot in diabetes.
AB  - The diabetic Charcot foot syndrome is a serious and potentially limb-threatening
      lower-extremity complication of diabetes. First described in 1883, this enigmatic
      condition continues to challenge even the most experienced practitioners. Now
      considered an inflammatory syndrome, the diabetic Charcot foot is characterized
      by varying degrees of bone and joint disorganization secondary to underlying
      neuropathy, trauma, and perturbations of bone metabolism. An international task
      force of experts was convened by the American Diabetes Association and the
      American Podiatric Medical Association in January 2011 to summarize available
      evidence on the pathophysiology, natural history, presentations, and treatment
      recommendations for this entity.

PMID- 21957277
TI  - Navicular stress reactions in runners: a review of evaluation and management of a
      competitive athlete.
AB  - Navicular stress injuries in athletes can be devastating. Clinical findings are
      frequently nonspecific until significant progression of the abnormality has
      occurred. The use of diagnostic imaging techniques early in the discovery period
      increases the likelihood of establishing an immediate diagnosis and avoids frank
      fracture of the navicular bone. Delayed diagnosis of navicular stress injuries in
      athletes can cause dire consequences. The physician must be aware of the injury
      in establishing a high index of clinical suspicion. The timing and sequencing of
      diagnostic imaging studies is essential in establishing a diagnosis to manage the
      patient and minimize time away from competition. This case study examines the
      history and management of an elite high school track athlete who sustained a
      navicular stress injury. The timing and use of diagnostic imaging studies is
      reviewed.

PMID- 21957278
TI  - Bilateral tibial hallux sesamoid agenesis and fibular hallux sesamoid hypoplasia
      in a patient with bilateral hallux valgus.
AB  - We report the clinical features, radiographic findings, management, and results
      of a patient with bilateral hallux valgus and associated bilateral tibial hallux
      sesamoid agenesis and fibular hallux sesamoid hypoplasia. Our patient was managed
      operatively with good clinical results. Combined tibial sesamoid agenesis and
      fibular sesamoid hypoplasia do not seem to negatively influence the management of
      hallux valgus.

PMID- 21957279
TI  - Lengthening of the midfoot in a case of lower-extremity hemimelia.
AB  - Hemimelia of the lower limb belongs to the group of congenital deficiency
      disorders. The clinical spectrum ranges from minimal shortening of the long bones
      to severe deficiencies of the extremities. Several etiologies, such as X-rays or
      drugs, have been implicated to be responsible for hemimelia. In the present
      report the clinical course and the long-term follow-up of a patient with
      transverse terminal hemimelia of the left foot at the level of the basis of the
      metatarsals is described. Due to frequent episodes of pain, development of
      pressure sores, and an increasing psychological burden, operative intervention
      consisting of a lengthening procedure using an Ilizarov fixator was indicated.
      Long-term outcome was good; the patient is now able to painlessly wear
      conventional shoes and displays a normal gait pattern.

PMID- 21957280
TI  - Mimicry in older patients: tophaceous pseudogout as a tumorlike lesion: a case
      report.
AB  - Pseudogout is frequently seen in painful arthritis of larger joints, especially
      the knees and shoulders. This case report describes a rare clinical entity of
      soft-tissue calcium pyrophosphate dihydrate crystal deposition disease
      surrounding the second metatarsal bone of an 81-year-old man with moderate
      painful swelling of the right forefoot for 2 years. Diagnostic imaging
      demonstrated a calcified soft-tissue tumor adjacent to the second metatarsal bone
      by considering a neoplastic process in the differential diagnosis. Excisional
      biopsy revealed a chalklike material on the calcified soft tissue that was
      pathognomonic for chondrocalcinosis or pseudogout. The excisional biopsy findings
      led to stagnation of the clinical symptoms, and no recurrence of the initial
      tumor was seen during 12-month follow-up. In the literature, only 28 cases of
      tophaceous pseudogout tumors in the extremities have been described. In these
      cases, the lesions were suspected of being chondrosarcomas. For this reason, a
      correct diagnosis has to be pursued by performing a biopsy to treat the disease
      correctly.

PMID- 21957281
TI  - H5N1-SeroDetect EIA and rapid test: a novel differential diagnostic assay for
      serodiagnosis of H5N1 infections and surveillance.
AB  - Continuing evolution of highly pathogenic (HP) H5N1 influenza viruses in wild
      birds with transmission to domestic poultry and humans poses a pandemic threat.
      There is an urgent need for a simple and rapid serological diagnostic assay which
      can differentiate between antibodies to seasonal and H5N1 strains and that could
      provide surveillance tools not dependent on virus isolation and nucleic acid
      technologies. Here we describe the establishment of H5N1 SeroDetect enzyme-linked
      immunosorbent assay (ELISA) and rapid test assays based on three peptides in HA2
      (488-516), PB1-F2 (2-75), and M2e (2-24) that are highly conserved within H5N1
      strains. These peptides were identified by antibody repertoire analyses of H5N1
      influenza survivors in Vietnam using whole-genome-fragment phage display
      libraries (GFPDLs). To date, both platforms have demonstrated high levels of
      sensitivity and specificity in detecting H5N1 infections (clade 1 and clade
      2.3.4) in Vietnamese patients as early as 7 days and up to several years
      postinfection. H5N1 virus-uninfected individuals in Vietnam and the United
      States, including subjects vaccinated with seasonal influenza vaccines or with
      confirmed seasonal virus infections, did not react in the H5N1-SeroDetect assays.
      Moreover, sera from individuals vaccinated with H5N1 subunit vaccine with
      moderate anti-H5N1 neutralizing antibody titers did not react positively in the
      H5N1-SeroDetect ELISA or rapid test assays. The simple H5N1-SeroDetect ELISA and
      rapid tests could provide an important tool for large-scale surveillance for
      potential exposure to HP H5N1 strains in both humans and birds.

PMID- 21957283
TI  - Regulation of vaccinia virus E3 protein by small ubiquitin-like modifier
      proteins.
AB  - The vaccinia virus (VACV) E3 protein is essential for virulence and has
      antiapoptotic activity and the ability to impair the host innate immune response.
      Here we demonstrate that E3 interacts with SUMO1 through a small ubiquitin-like
      modifier (SUMO)-interacting motif (SIM). SIM integrity is required for
      maintaining the stability of the viral protein and for the covalent conjugation
      of E3 to SUMO1 or SUMO2, a modification that has a negative effect on the E3
      transcriptional transactivation of the p53-upregulated modulator of apoptosis
      (PUMA) and APAF-1 genes. We also demonstrate that E3 is ubiquitinated, a
      modification that does not destabilize the wild-type protein but triggers the
      degradation of an E3-DeltaSIM mutant. This report constitutes the first
      demonstration of the important roles that both SUMO and ubiquitin play in the
      regulation of the VACV protein E3.

PMID- 21957284
TI  - The cellular protein lyric interacts with HIV-1 Gag.
AB  - Human immunodeficiency virus type 1 (HIV-1) Gag is the main structural protein
      driving assembly and release of virions from infected cells. Gag alone is capable
      of self-assembly in vitro, but host factors have been shown to play a role in
      efficient viral replication and particle morphogenesis within the living cell. In
      a series of affinity purification experiments, we identified the cellular protein
      Lyric to be an HIV-1 Gag-interacting protein. Lyric was previously described to
      be an HIV-inducible gene and is involved in various signaling pathways. Gag
      interacts with endogenous Lyric via its matrix (MA) and nucleocapsid (NC)
      domains. This interaction requires Gag multimerization and Lyric amino acids 101
      to 289. Endogenous Lyric is incorporated into HIV-1 virions and is cleaved by the
      viral protease. Gag-Lyric interaction was also observed for murine leukemia virus
      and equine infectious anemia virus, suggesting that it represents a conserved
      feature among retroviruses. Expression of the Gag binding domain of Lyric
      increased Gag expression levels and viral infectivity, whereas expression of a
      Lyric mutant lacking the Gag binding site resulted in lower Gag expression and
      decreased viral infectivity. The results of the current study identify Lyric to
      be a cellular interaction partner of HIV-1 Gag and hint at a potential role in
      regulating infectivity. Further experiments are needed to elucidate the precise
      role of this interaction.

PMID- 21957285
TI  - RNA-based immunity terminates viral infection in adult Drosophila in the absence
      of viral suppression of RNA interference: characterization of viral small
      interfering RNA populations in wild-type and mutant flies.
AB  - Replication of viral RNA genomes in fruit flies and mosquitoes induces the
      production of virus-derived small interfering RNAs (siRNAs) to specifically
      reduce virus accumulation by RNA interference (RNAi). However, it is unknown
      whether the RNA-based antiviral immunity (RVI) is sufficiently potent to
      terminate infection in adult insects as occurs in cell culture. We show here
      that, in contrast to robust infection by Flock house virus (FHV), infection with
      an FHV mutant (FHVDeltaB2) unable to express its RNAi suppressor protein B2 was
      rapidly terminated in adult flies. FHVDeltaB2 replicated to high levels and
      induced high mortality rates in dicer-2 and argonaute-2 mutant flies that are
      RNAi defective, demonstrating that successful infection of adult Drosophila
      requires a virus-encoded activity to suppress RVI. Drosophila RVI may depend on
      the RNAi activity of viral siRNAs since efficient FHVDeltaB2 infection occurred
      in argonaute-2 and r2d2 mutant flies despite massive production of viral siRNAs.
      However, RVI appears to be insensitive to the relative abundance of viral siRNAs
      since FHVDeltaB2 infection was terminated in flies carrying a partial loss-of
      function mutation in loquacious required for viral siRNA biogenesis. Deep
      sequencing revealed a low-abundance population of Dicer-2-dependent viral siRNAs
      accompanying FHVDeltaB2 infection arrest in RVI-competent flies that included an
      approximately equal ratio of positive and negative strands. Surprisingly, viral
      small RNAs became strongly biased for positive strands at later stages of
      infection in RVI-compromised flies due to genetic or viral suppression of RNAi.
      We propose that degradation of the asymmetrically produced viral positive-strand
      RNAs associated with abundant virus accumulation contributes to the positive
      strand bias of viral small RNAs.

PMID- 21957287
TI  - Analysis of a neutralizing antibody for human herpesvirus 6B reveals a role for
      glycoprotein Q1 in viral entry.
AB  - Human herpesvirus 6 (HHV-6) is a T cell-tropic betaherpesvirus. HHV-6 can be
      classified into two variants, HHV-6A and HHV-6B, based on differences in their
      genetic, antigenic, and growth characteristics and cell tropisms. The function of
      HHV-6B should be analyzed more in its life cycle, as more than 90% of people have
      the antibodies for HHV-6B but not HHV-6A. It has been shown that the cellular
      receptor for HHV-6A is human CD46 and that the viral ligand for CD46 is the
      envelope glycoprotein complex gH/gL/gQ1/gQ2; however, the receptor-ligand pair
      used by HHV-6B is still unknown. In this study, to identify the glycoprotein(s)
      important for HHV-6B entry, we generated monoclonal antibodies (MAbs) that
      inhibit infection by HHV-6B. Most of these MAbs were found to recognize gQ1,
      indicating that HHV-6B gQ1 is critical for virus entry. Interestingly, the
      recognition of gQ1 by the neutralizing MAb was enhanced by coexpression with gQ2.
      Moreover, gQ1 deletion or point mutants that are not recognized by the MAb could
      nonetheless associate with gQ2, indicating that although the MAb recognized the
      conformational epitope of gQ1 exposed by the gQ2 interaction, this epitope was
      not related to the gQ2 binding domain. Our study shows that HHV-6B gQ1 is likely
      a ligand for the HHV-6B receptor, and the recognition site for this MAb will be a
      promising target for antiviral agents.

PMID- 21957286
TI  - Immunovirological analyses of chronically simian immunodeficiency virus SIVmnd-1-
      and SIVmnd-2-infected mandrills (Mandrillus sphinx).
AB  - Simian immunodeficiency virus (SIV) infection in African nonhuman primate (NHP)
      natural hosts is usually nonpathogenic, despite high levels of virus replication.
      We have previously shown that chronic SIV infection in sooty mangabeys (SMs) and
      African green monkeys (AGMs) is associated with low levels of immune activation
      and bystander T cell apoptosis. To compare these features with those observed in
      another natural host, the mandrill (MND), we conducted a cross-sectional survey
      of the 23 SIV-infected and 25 uninfected MNDs from the only semifree colony of
      mandrills available worldwide. Viral loads (VLs) were determined and phenotypic
      and functional analysis of peripheral blood- and lymph node-derived lymphocytes
      was performed. We found that mandrills chronically infected with SIVmnd-1 or
      SIVmnd-2 have similar levels of viral replication, and we observed a trend toward
      lower CD4+ T cell counts in chronically SIVmnd-2-infected MNDs than SIVmnd-1
      infected MNDs. No correlation between CD4+ T cell counts and VLs in SIV-infected
      MNDs could be established. Of note, the levels of T cell activation,
      proliferation, and apoptosis were comparable between SIVmnd-1- and SIVmnd-2
      infected MNDs and to those observed in uninfected animals, with the only
      exception being an increase in tumor necrosis factor alpha-producing CD8+ T cells
      in SIVmnd-2-infected MNDs. Overall, these findings recapitulate previous
      observations in SIV-infected SMs and AGMs and lend further evidence to the
      hypothesis that low levels of immune activation protect natural SIV hosts from
      disease progression.

PMID- 21957288
TI  - Adeno-associated virus activates an innate immune response in normal human cells
      but not in osteosarcoma cells.
AB  - Adeno-associated virus (AAV) is a small, DNA-containing dependovirus with
      promising potential as a gene delivery vehicle. Given the variety of applications
      of AAV-based vectors in the treatment of genetic disorders, numerous studies have
      focused on the immunogenicity of recombinant AAV. In general, AAV vectors appear
      not to induce strong inflammatory responses. We have found that AAV2, when it
      infects the osteosarcoma cells U2OS, can initiate part of its replicative cycle
      in the absence of helper virus. This does not occur in untransformed cells. We
      set out to test whether the cellular innate antiviral defenses control this
      susceptibility and found that, in nonimmune normal human fibroblasts, AAV2
      induces type I interferon production and release and the accumulation of nuclear
      promyelocytic leukemia bodies. AAV fails to mobilize this defense pathway in the
      U2OS cells. This permissiveness is in large part due to impairment of the viral
      sensing machinery in these cells. Our investigations point to Toll-like receptor
      9 as a potential intracellular sensor that detects AAV2 and triggers the
      antiviral state in AAV-infected untransformed cells. Efficient sensing of the AAV
      genome and the ensuing activation of an innate antiviral response are thus
      crucial cellular events dictating the parvovirus infectivity in host cells.

PMID- 21957289
TI  - Kaposi's sarcoma-associated herpesvirus noncoding polyadenylated nuclear RNA
      interacts with virus- and host cell-encoded proteins and suppresses expression of
      genes involved in immune modulation.
AB  - During lytic infection, Kaposi's sarcoma-associated herpesvirus (KSHV) expresses
      a polyadenylated nuclear RNA (PAN RNA). This noncoding RNA (ncRNA) is localized
      to the nucleus and is the most abundant viral RNA during lytic infection;
      however, to date, the role of PAN RNA in the virus life cycle is unknown. Many
      examples exist where ncRNAs have a defined key regulatory function controlling
      gene expression by various mechanisms. Our goal for this study was to identify
      putative binding partners for PAN RNA in an effort to elucidate a possible
      function for the transcript in KSHV infection. We employed an in vitro affinity
      protocol where PAN RNA was used as bait for factors present in BCBL-1 cell
      nuclear extract to show that PAN RNA interacts with several virus- and host cell
      encoded factors, including histones H1 and H2A, mitochondrial and cellular single
      stranded binding proteins (SSBPs), and interferon regulatory factor 4 (IRF4). RNA
      chromatin immunoprecipitation (ChIP) assays confirmed that PAN RNA interacted
      with these factors in the infected cell environment. A luciferase reporter assay
      showed that PAN RNA expression interfered with the ability of IRF4/PU.1 to
      activate the interleukin-4 (IL-4) promoter, strongly suggesting a role for PAN
      RNA in immune modulation. Since the proteomic screen and functional data
      suggested a role in immune responses, we investigated if constitutive PAN RNA
      expression could affect other genes involved in immune responses. PAN RNA
      expression decreased expression of gamma interferon, interleukin-18, alpha
      interferon 16, and RNase L. These data strongly suggest that PAN RNA interacts
      with viral and cellular proteins and can function as an immune modulator.

PMID- 21957290
TI  - Target cell-mediated editing of HIV-1 cDNA by APOBEC3 proteins in human
      macrophages.
AB  - Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3)
      proteins are encapsidated by assembling HIV-1 virions and edit viral cDNA in the
      next round of infection. Using alpha interferon (IFN-alpha)-treated monocyte
      derived macrophages, we show that infrequent editing of HIV-1 reverse transcripts
      can also be mediated by APOBEC3 proteins supplied by the targets of infection.
      Based on the local sequence contexts of these mutations and the established
      characteristics of APOBEC3 protein expression in myeloid cells, we speculate that
      APOBEC3A may be responsible for a substantial proportion of this activity.

PMID- 21957291
TI  - In vitro generation of high-titer prions.
AB  - Prions are composed mainly, if not entirely, of PrP(Sc), an infectious misfolded
      isoform of PrP(C), the normal isoform of the prion protein. Here we show that
      protein misfolding cyclic amplification (PMCA)-generated hypertransmissible mink
      encephalopathy (HY TME) PrP(Sc) is highly infectious and has a titer that is
      similar, if not identical, to that associated with brain tissue from animals
      infected with the HY TME agent that are in the terminal stage of disease. These
      data demonstrate that PMCA efficiently replicates the prion agent and provide
      further support for the hypothesis that in vitro-generated prions are bona fide
      and are not due to contamination.

PMID- 21957292
TI  - Autophagy required for hepatitis B virus replication in transgenic mice.
AB  - Recent studies indicate that hepatitis B virus (HBV) may induce autophagy to
      enhance its replication in cell cultures. To understand whether autophagy can
      indeed enhance HBV replication in vivo, we generated HBV transgenic mice with
      liver-specific knockout of the Atg5 gene, a gene critical for the initiation of
      autophagy. Immunoblot analyses confirmed the inhibition of autophagy in the
      livers of Atg5 knockout mice. This inhibition of autophagy slightly reduced HBV
      gene expression and affected nuclear localization of the HBV core protein. It
      also reduced the HBV DNA level in sera by more than 90% and the level of the HBV
      DNA replicative intermediate in the mouse liver to an almost undetectable level.
      Our results thus demonstrate that autophagy is important for HBV replication in
      vivo and raise the possibility of targeting this pathway to treat HBV patients.

PMID- 21957293
TI  - Hypoxia induces the gene expression and extracellular transmission of persistent
      lymphocytic choriomeningitis virus.
AB  - The physiological context of virus-infected cells can markedly affect
      multiplication and spread of the virus progeny. During persistent infection, the
      virus exploits the host cell without disturbing its vital functions. However,
      microenvironmental hypoxia can uncouple this intimate relationship and escalate
      virus pathogenesis. Accumulating evidence suggests that hypoxia-inducible factor
      (HIF) modulates gene expression of the viruses that pass through a DNA stage,
      contain hypoxia-responsive promoter elements, and replicate in the nucleus. Here
      we show that hypoxia can influence the gene expression and transmission of the
      cytoplasmic RNA virus lymphocytic choriomeningitis virus (LCMV), which is a
      neglected human pathogen and teratogen. The MX strain of LCMV, which we used as a
      model, replicates in a persistent mode in human HeLa cells, fails to produce
      mature envelope glycoproteins, and spreads through cell-cell contacts in the
      absence of extracellular infectious virions. Both exposure of MX-infected HeLa
      cells to chronic hypoxia and gene transfer approaches led to increased virus RNA
      transcription and higher levels of the viral proteins via a HIF-dependent
      mechanism. Moreover, hypoxia enhanced the formation of infectious virions capable
      of transmitting LCMV by cell-free medium. This LCMV "reactivation" might have
      health-compromising consequences in hypoxia-associated situations, such as fetal
      development and ischemia-related pathologies.

PMID- 21957295
TI  - CD8+ T cell immunodominance in lymphocytic choriomeningitis virus infection is
      modified in the presence of toll-like receptor agonists.
AB  - Currently, we have limited understanding of how Toll-like receptor (TLR)
      engagement by microbial products influences the immune response during a
      concurrent virus infection. In this study, we established that dual TLR2 plus
      TLR3 (designated TLR2+3) stimulation alters the immunodominance hierarchies of
      lymphocytic choriomeningitis virus (LCMV) epitopes by reducing NP396-specific
      CD8+ T cell responses and shifting it to a subdominant position. The shift in
      immunodominance occurred due to a reduction in antigen uptake and the reduced
      cross-presentation of NP396, a major LCMV immunodominant epitope that is
      efficiently cross-presented. Moreover, the altered immunodominance was dependent
      on TLR stimulation occurring at the site of infection. Finally, as
      lipopolysaccharide failed to induce the same phenomenon, the data suggest that
      these findings are dependent not only on the dual engagement of the TRIF/MyD88
      pathways but also on how TLR agonists activate antigen-presenting cells. Taken
      together, our data demonstrate a novel role for TLR ligands in regulating
      antiviral CD8+ T cell responses due to the regulation of the cross-presentation
      of cell-associated antigens.

PMID- 21957294
TI  - Targeting of the influenza A virus polymerase PB1-PB2 interface indicates strain
      specific assembly differences.
AB  - Assembly of the heterotrimeric influenza virus polymerase complex from the
      individual subunits PB1, PA, and PB2 is a prerequisite for viral replication. The
      conserved protein-protein interaction sites have been suggested as potential drug
      targets. To characterize the PB1-PB2 interface, we fused the PB1-binding domain
      of PB2 to green fluorescent protein (PB2(1-37)-GFP) and determined its
      competitive inhibitory effect on the polymerase activity of influenza A virus
      strains. Coexpression of PB2(1-37)-GFP in a polymerase reconstitution system led
      to substantial inhibition of the polymerase of A/WSN/33 (H1N1). Surprisingly,
      polymerases of other strains, including A/SC35M (H7N7), A/Puerto Rico/8/34
      (H1N1), A/Hamburg/4/2009 (H1N1), and A/Thailand/1(KAN-1)/2004 (H5N1), showed
      various degrees of resistance. Individual exchange of polymerase subunits and the
      nucleoprotein between the sensitive WSN polymerase and the insensitive SC35M
      polymerase mapped the resistance to both PB1 and PA of SC35M polymerase. While
      PB2(1-37)-GFP bound equally well to the PB1 subunits of both virus strains, PB1
      PA dimers of SC35M polymerase showed impaired binding compared to PB1-PA dimers
      of WSN polymerase. The use of PA(SC35M/WSN) chimeras revealed that the reduced
      affinity of the SC35M PB1-PA dimer was mediated by the N-terminal 277 amino acids
      of PA. Based on these observations, we speculate that the PB1-PA dimer formation
      of resistant polymerases shields the PB2(1-37) binding site, whereas sensitive
      polymerases allow this interaction, suggesting different assembly strategies of
      the trimeric polymerase complex between different influenza A virus strains.

PMID- 21957296
TI  - A domain in the herpes simplex virus 1 triplex protein VP23 is essential for
      closure of capsid shells into icosahedral structures.
AB  - VP23 is a key component of the triplex structure. The triplex, which is unique to
      herpesviruses, is a complex of three proteins, two molecules of VP23 which
      interact with a single molecule of VP19C. This structure is important for shell
      accretion and stability of the protein coat. Previous studies utilized a random
      transposition mutagenesis approach to identify functional domains of the triplex
      proteins. In this study, we expand on those findings to determine the key amino
      acids of VP23 that are required for triplex formation. Using alanine-scanning
      mutagenesis, we have made mutations in 79 of 318 residues of the VP23
      polypeptide. These mutations were screened for function both in the yeast two
      hybrid assay for interaction with VP19C and in a genetic complementation assay
      for the ability to support the replication of a VP23 null mutant virus. These
      assays identified a number of amino acids that, when altered, abolish VP23
      function. Abrogation of virus assembly by a single-amino-acid change bodes well
      for future development of small-molecule inhibitors of this process. In addition,
      a number of mutations which localized to a C-terminal region of VP23 (amino acids
      205 to 241) were still able to interact with VP19C but were lethal for virus
      replication when introduced into the herpes simplex virus 1 (HSV-1) KOS genome.
      The phenotype of many of these mutant viruses was the accumulation of large open
      capsid shells. This is the first demonstration of capsid shell accumulation in
      the presence of a lethal VP23 mutation. These data thus identify a new domain of
      VP23 that is required for or regulates capsid shell closure during virus
      assembly.

PMID- 21957297
TI  - Identification of a Cullin5-ElonginB-ElonginC E3 complex in degradation of feline
      immunodeficiency virus Vif-mediated feline APOBEC3 proteins.
AB  - Various feline APOBEC3 (fA3) proteins exhibit broad antiviral activities against
      a wide range of viruses, such as feline immunodeficiency virus (FIV), feline
      foamy virus (FFV), and feline leukemia virus (FeLV), as well as those of other
      species. This activity can be counteracted by the FIV Vif protein, but the
      mechanism by which FIV Vif suppresses fA3s is unknown. In the present study, we
      demonstrated that FIV Vif could act via a proteasome-dependent pathway to
      overcome fA3s. FIV Vif interacted with feline cellular proteins Cullin5 (Cul5),
      ElonginB, and ElonginC to form an E3 complex to induce degradation of fA3s. Both
      the dominant-negative Cul5 mutant and a C-terminal hydrophilic replacement
      ElonginC mutant potently disrupted the FIV Vif activity against fA3s.
      Furthermore, we identified a BC-box motif in FIV Vif that was essential for the
      recruitment of E3 ubiquitin ligase and also required for FIV Vif-mediated
      degradation of fA3s. Moreover, despite the lack of either a Cul5-box or a HCCH
      zinc-binding motif, FIV Vif specifically selected Cul5. Therefore, FIV Vif may
      interact with Cul5 via a novel mechanism. These finding imply that SOCS proteins
      may possess distinct mechanisms to bind Cul5 during formation of the Elongin
      Cullin-SOCS box complex.

PMID- 21957298
TI  - Modulation of NKG2D-mediated cytotoxic functions of natural killer cells by viral
      protein R from HIV-1 primary isolates.
AB  - HIV-1 viral protein R (Vpr) from laboratory-adapted virus strains activates the
      DNA damage/stress sensor ATR kinase and induces cell cycle arrest at the G(2)/M
      phase through a process that requires Vpr to engage the DDB1-CUL4A (VprBP/DCAF-1)
      E3 ligase complex. Activation of this DNA damage/stress checkpoint in G(2) by Vpr
      was shown to modulate NKG2D-dependent NK cell effector functions via enhancing
      expression of NKG2D ligands, notably ULBP2. However, it is unknown whether Vpr
      from HIV-1 primary isolates (groups M, N, O, and P) could modulate NKG2D-mediated
      cytotoxic functions of NK cells. Here, we report that Vpr from most HIV-1 primary
      isolates can upregulate ULBP2 expression and induce NKG2D-dependent NK cell
      killing. Importantly, these activities were always accompanied by an active G(2)
      cell cycle arrest function. Interestingly, Vpr variants from group P and a clade
      D isolate of group M were defective at enhancing NKG2D-mediated NK cell lysis
      owing to their inability to augment ULBP2 expression. However, distinct
      mechanisms were responsible for their failure to do so. While Vpr from group P
      was deficient in its ability to engage the DDB1-CUL4A (VprBP/DCAF-1) E3 ligase
      complex, the Vpr variant from group D was unable to properly localize to the
      nucleus, underlining the importance of these biological properties in Vpr
      function. In conclusion, the ability of Vpr from HIV-1 primary isolates to
      regulate NK cell effector function underscores the importance of this HIV-1
      accessory protein in the modulation of the host's innate immune responses.

PMID- 21957299
TI  - A multifunctional protein encoded by turkey herpesvirus suppresses RNA silencing
      in Nicotiana benthamiana.
AB  - Many plant and animal viruses counteract RNA silencing-mediated defense by
      encoding diverse RNA silencing suppressors. We characterized HVT063, a
      multifunctional protein encoded by turkey herpesvirus (HVT), as a silencing
      suppressor in coinfiltration assays with green fluorescent protein transgenic
      Nicotiana benthamiana line 16c. Our results indicated that HVT063 could strongly
      suppress both local and systemic RNA silencing induced by either sense RNA or
      double-stranded RNA (dsRNA). HVT063 could reverse local silencing, but not
      systemic silencing, in newly emerging leaves. The local silencing suppression
      activity of HVT063 was also verified using the heterologous vector PVX. Further,
      single alanine substitution of arginine or lysine residues of the HVT063 protein
      showed that each selected single amino acid contributed to the suppression
      activity of HVT063 and region 1 (residues 138 to 141) was more important, because
      three of four single amino acid mutations in this region could abolish the
      silencing suppressor activity of HVT063. Moreover, HVT063 seemed to induce a cell
      death phenotype in the infiltrated leaf region, and the HVT063 dilutions could
      decrease the silencing suppressor activity and alleviate the cell death
      phenotype. Collectively, these results suggest that HVT063 functions as a viral
      suppressor of RNA silencing that targets a downstream step of the dsRNA formation
      in the RNA silencing process. Positively charged amino acids in HVT063, such as
      arginine and lysine, might contribute to the suppressor activity by boosting the
      interaction between HVT063 and RNA, since HVT063 has been demonstrated to be an
      RNA binding protein.

PMID- 21957300
TI  - Epstein-Barr virus BamHI W repeat number limits EBNA2/EBNA-LP coexpression in
      newly infected B cells and the efficiency of B-cell transformation: a rationale
      for the multiple W repeats in wild-type virus strains.
AB  - The genome of Epstein-Barr virus (EBV), a gammaherpesvirus with potent B-cell
      growth-transforming ability, contains multiple copies of a 3-kb BamHI W repeat
      sequence; each repeat carries (i) a promoter (Wp) that initiates transformation
      by driving EBNA-LP and EBNA2 expression and (ii) the W1W2 exons encoding the
      functionally active repeat domain of EBNA-LP. The W repeat copy number of a virus
      therefore influences two potential determinants of its transforming ability: the
      number of available Wp copies and the maximum size of the encoded EBNA-LP. Here,
      using recombinant EBVs, we show that optimal B-cell transformation requires a
      minimum of 5 W repeats (5W); the levels of transforming ability fall
      progressively with viruses carrying 4, 3, and 2 W repeats, as do the levels of Wp
      initiated transcripts expressed early postinfection (p.i.), while viruses with 1
      copy of the wild-type W repeat (1W) and 0W are completely nontransforming. We
      therefore suggest that genetic analyses of EBV transforming function should
      ensure that wild-type and mutant strains have equal numbers (ideally at least 5)
      of W copies if the analysis is not to be compromised. Attempts to enhance the
      transforming function of low-W-copy-number viruses, via the activity of helper
      EBV strains or by gene repair, suggested that the critical defect is not related
      to EBNA-LP size but to the failure to achieve sufficiently strong coexpression of
      EBNA-LP and EBNA2 early postinfection. We further show by the results of ex vivo
      assays that EBV strains in the blood of infected individuals typically have a
      mean of 5 to 8 W copies, consistent with the view that evolution has selected for
      viruses with an optimal transforming function.

PMID- 21957301
TI  - Fusion of Epstein-Barr virus with epithelial cells can be triggered by
      alphavbeta5 in addition to alphavbeta6 and alphavbeta8, and integrin binding
      triggers a conformational change in glycoproteins gHgL.
AB  - Fusion of herpesviruses with their target cells requires a minimum of three
      glycoproteins, namely, gB and a complex of gH and gL. Epstein-Barr virus (EBV)
      fusion with an epithelial cell requires no additional virus glycoproteins, and we
      have shown previously that it can be initiated by an interaction between integrin
      alphavbeta6 or alphavbeta8 and gHgL. We now report that integrin alphavbeta5 can
      also bind to gHgL and trigger fusion. Binding of gHgL to integrins is a two-step
      reaction. The first step, analyzed by surface plasmon resonance, was fast, with
      high association and low dissociation rate constants. The second step, detected
      by fluorescence spectroscopy of gHgL labeled at cysteine 153 at the domain I
      domain II interface with the environmentally sensitive probes acrylodan and
      IANBD, involved a slower conformational change. Interaction of gHgL with
      neutralizing monoclonal antibodies or Fab' fragments was also consistent with a
      two-step reaction involving fast high-affinity binding and a subsequent slower
      conformational change. None of the antibodies bound to the same epitope, and none
      completely inhibited integrin binding. However, binding of each decreased the
      rate of conformational change induced by integrin binding, suggesting that
      neutralization might involve a conformational change that precludes fusion.
      Overall, the data are consistent with the interaction of gHgL with an integrin
      inducing a functionally important rearrangement at the domain I-domain II
      interface.

PMID- 21957302
TI  - Creation of a nonspreading Rift Valley fever virus.
AB  - Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic bunyavirus of the
      genus Phlebovirus and a serious human and veterinary pathogen. RVFV contains a
      three-segmented RNA genome, which is comprised of the large (L), medium (M), and
      small (S) segments. The proteins that are essential for genome replication are
      encoded by the L and S segments, whereas the structural glycoproteins are encoded
      by the M segment. We have produced BHK replicon cell lines (BHK-Rep) that
      maintain replicating L and S genome segments. Transfection of BHK-Rep cells with
      a plasmid encoding the structural glycoproteins results in the efficient
      production of RVFV replicon particles (RRPs). To facilitate monitoring of
      infection, the NSs gene was replaced with an enhanced green fluorescent protein
      gene. RRPs are infectious for both mammalian and insect cells but are incapable
      of autonomous spreading, rendering their application outside biosafety
      containment completely safe. We demonstrate that a single intramuscular
      vaccination with RRPs protects mice from a lethal dose of RVFV and show that RRPs
      can be used for rapid virus neutralization tests that do not require
      biocontainment facilities. The methods reported here will greatly facilitate
      vaccine and drug development as well as fundamental studies on RVFV biology.
      Moreover, it may be possible to develop similar systems for other members of the
      bunyavirus family as well.

PMID- 21957303
TI  - Poliovirus unlinks TIA1 aggregation and mRNA stress granule formation.
AB  - In response to environmental stress and viral infection, mammalian cells form
      foci containing translationally silenced mRNPs termed stress granules (SGs). As
      aggregates of stalled initiation complexes, SGs are defined by the presence of
      translation initiation machinery in addition to mRNA binding proteins. Here, we
      report that cells infected with poliovirus (PV) can form SGs early that contain T
      cell-restricted intracellular antigen 1 (TIA1), translation initiation factors,
      RNA binding proteins, and mRNA. However, this response is blocked as infection
      progresses, and a type of pseudo-stress granule remains at late times
      postinfection and contains TIA but lacks translation initiation factors, mRNA
      binding proteins, and most polyadenylated mRNA. This result was observed using
      multiple stressors, including viral infection, oxidative stress, heat shock, and
      endoplasmic reticulum stress. Multiple proteins required for efficient viral
      internal ribosome entry site-dependent translation are localized to SGs under
      stress conditions, providing a potential rationale for the evolution and
      maintenance of the SG inhibition phenotype. Further, the expression of a
      noncleavable form of the RasGAP-SH3 domain binding protein in PV-infected cells
      enables SGs whose constituents are consistent with the presence of stalled 48S
      translation preinitiation complexes to persist throughout infection. These
      results indicate that in poliovirus-infected cells, the functions of TIA self
      aggregation and aggregation of stalled translation initiation complexes into
      stress granules are severed, leading to novel foci that contain TIA1 but lack
      other stress granule-defining components.

PMID- 21957304
TI  - Adenovirus with hexon Tat-protein transduction domain modification exhibits
      increased therapeutic effect in experimental neuroblastoma and neuroendocrine
      tumors.
AB  - Adenovirus serotype 5 (Ad5) is widely used as an oncolytic agent for cancer
      therapy. However, its infectivity is highly dependent on the expression level of
      coxsackievirus-adenovirus receptor (CAR) on the surfaces of tumor cells.
      Furthermore, infected cells overproduce adenovirus fiber proteins, which are
      released prior to cell lysis. The released fibers block CAR on noninfected
      neighboring cells, thereby preventing progeny virus entry. Our aim was to add a
      CAR-independent infection route to Ad5 to increase the infectivity of tumor cells
      with low CAR expression and prevent the fiber-masking problem. We constructed Ad5
      viruses that encode the protein transduction domain (PTD) of the HIV-1 Tat
      protein (Tat-PTD) in hypervariable region 5 (HVR5) of the hexon protein. Tat-PTD
      functions as a cell-penetrating peptide, and Tat-PTD-modified Ad5 showed a
      dramatic increased transduction of CAR-negative cell lines compared to unmodified
      vector. Moreover, while tumor cell infectivity was severely reduced for Ad5 in
      the presence of fiber proteins, it was only marginally reduced for Tat-PTD
      modified Ad5. Furthermore, because of the sequence alteration in the hexon HVR,
      coagulation factor X-mediated virus uptake was significantly reduced. Mice
      harboring human neuroblastoma and neuroendocrine tumors show suppressed tumor
      growths and prolonged survival when treated with Tat-PTD-modified oncolytic
      viruses. Our data suggest that modification of Ad5 with Tat-PTD in HVR5 expands
      its utility as an oncolytic agent.

PMID- 21957305
TI  - Molecular determinants of arenavirus Z protein homo-oligomerization and L
      polymerase binding.
AB  - The arenavirus Z is a zinc-binding RING protein that has been implicated in
      multiple functions during the viral life cycle. These roles of Z involve
      interactions with viral and cellular proteins that remain incompletely
      understood. In this regard, Z inhibits viral RNA transcription and replication
      through direct interaction with the viral L polymerase. Here, we defined the L
      binding domain of Tacaribe virus (TCRV) Z protein and the structural requirements
      mediating Z homo-oligomerization. By using site-directed mutagenesis,
      coimmunoprecipitation, and functional assays, we showed that residues R37, N39,
      W44, L50, and Y57, located around the zinc coordination site I, play a critical
      role in the Z-L interaction. We also found that Z protein from either TCRV or the
      pathogenic Junin virus (JUNV) self-associates into oligomeric forms in mammalian
      cells. Importantly, mutation of the myristoylation site, the strictly conserved
      residue G at position 2, severely impaired the ability of both TCRV Z and JUNV Z
      to self-interact as well as their capacity to accumulate at the plasma membrane,
      strongly suggesting that Z homo-oligomerization is associated with its
      myristoylation and cell membrane targeting. In contrast, disruption of the RING
      structure or substitution of W44 or N39, which are critical for L protein
      recognition, did not affect Z self-binding. Overall, the data presented here
      indicate that homo-oligomerization is not a requirement for Z-L interaction or Z
      mediated polymerase activity inhibition.

PMID- 21957306
TI  - Hepatitis C virus nucleotide inhibitors PSI-352938 and PSI-353661 exhibit a novel
      mechanism of resistance requiring multiple mutations within replicon RNA.
AB  - PSI-352938, a cyclic phosphate nucleotide, and PSI-353661, a phosphoramidate
      nucleotide, are prodrugs of beta-D-2'-deoxy-2'-alpha-fluoro-2'-beta-C
      methylguanosine-5'-monophosphate. Both compounds are metabolized to the same
      active 5'-triphosphate, PSI-352666, which serves as an alternative substrate
      inhibitor of the NS5B RNA-dependent RNA polymerase during HCV replication. PSI
      352938 and PSI-353661 retained full activity against replicons containing the
      S282T substitution, which confers resistance to certain 2'-substituted
      nucleoside/nucleotide analogs. PSI-352666 was also similarly active against both
      wild-type and S282T NS5B polymerases. In order to identify mutations that confer
      resistance to these compounds, in vitro selection studies were performed using
      HCV replicon cells. While no resistant genotype 1a or 1b replicons could be
      selected, cells containing genotype 2a JFH-1 replicons cultured in the presence
      of PSI-352938 or PSI-353661 developed resistance to both compounds. Sequencing of
      the NS5B region identified a number of amino acid changes, including S15G, R222Q,
      C223Y/H, L320I, and V321I. Phenotypic evaluation of these mutations indicated
      that single amino acid changes were not sufficient to significantly reduce the
      activity of PSI-352938 and PSI-353661. Instead, a combination of three amino acid
      changes, S15G/C223H/V321I, was required to confer a high level of resistance. No
      cross-resistance exists between the 2'-F-2'-C-methylguanosine prodrugs and other
      classes of HCV inhibitors, including 2'-modified nucleoside/-tide analogs such as
      PSI-6130, PSI-7977, INX-08189, and IDX-184. Finally, we determined that in
      genotype 1b replicons, the C223Y/H mutation failed to support replication, and
      although the A15G/C223H/V321I triple mutation did confer resistance to PSI-352938
      and PSI-353661, this mutant replicated at only about 10% efficiency compared to
      the wild type.

PMID- 21957307
TI  - Myxoma virus lacking the pyrin-like protein M013 is sensed in human myeloid cells
      by both NLRP3 and multiple Toll-like receptors, which independently activate the
      inflammasome and NF-kappaB innate response pathways.
AB  - The myxoma virus (MYXV)-encoded pyrin domain-containing protein M013 coregulates
      inflammatory responses mediated by both the inflammasome and the NF-kappaB
      pathways. Infection of human THP-1 monocytic cells with a MYXV construct deleted
      for the M013 gene (vMyxM013-KO), but not the parental MYXV, activates both the
      inflammasome and NF-kappaB pathways and induces a spectrum of proinflammatory
      cytokines and chemokines, like interleukin-1beta (IL-1beta), tumor necrosis
      factor (TNF), IL-6, and monocyte chemoattractant protein 1. Here, we report that
      vMyxM013-KO virus-mediated activation of inflammasomes and secretion of IL-1beta
      are dependent on the adaptor protein ASC, caspase-1, and NLRP3 receptor. However,
      vMyxM013-KO virus-mediated activation of NF-kappaB signaling, which induces TNF
      secretion, was independent of ASC, caspase-1, and either the NLRP3 or AIM2
      inflammasome receptors. We also report that early synthesis of pro-IL-1beta in
      response to vMyxM013-KO infection is dependent upon the components of the
      inflammasome complex. Activation of the NLRP3 inflammasome and secretion of IL
      1beta was also dependent on the release of cathepsin B and production of reactive
      oxygen species (ROS). By using small interfering RNA screening, we further
      demonstrated that, among the RIG-I-like receptors (RLRs) and Toll-like receptors
      (TLRs), only TLR2, TLR6, TLR7, and TLR9 contribute to the NF-kappaB-dependent
      secretion of TNF and the inflammasome-dependent secretion of IL-1beta in response
      to vMyxM013-KO virus infection. Additionally, we demonstrate that early
      triggering of the mitogen-activated protein kinase pathway by vMyxM013-KO virus
      infection of THP-1 cells plays a critical common upstream role in the coordinate
      induction of both NF-kappaB and inflammasome pathways. We conclude that an
      additional cellular sensor(s)/receptor(s) in addition to the known RLRs/TLRs
      plays a role in the M013 knockout virus-induced activation of NF-kappaB pathway
      signaling, but the activation of inflammasomes entirely depends on sensing by the
      NLRP3 receptor in response to vMyxM013-KO infection of human myeloid cells.

PMID- 21957308
TI  - Avian coronavirus in wild aquatic birds.
AB  - We detected a high prevalence (12.5%) of novel avian coronaviruses in aquatic
      wild birds. Phylogenetic analyses of these coronaviruses suggest that there is a
      diversity of gammacoronaviruses and deltacoronaviruses circulating in birds.
      Gammacoronaviruses were found predominantly in Anseriformes birds, whereas
      deltacoronaviruses could be detected in Ciconiiformes, Pelecaniformes, and
      Anseriformes birds in this study. We observed that there are frequent
      interspecies transmissions of gammacoronaviruses between duck species. In
      contrast, deltacoronaviruses may have more stringent host specificities. Our
      analysis of these avian viral and host mitochondrial DNA sequences also suggests
      that some, but not all, coronaviruses may have coevolved with birds from the same
      order.

PMID- 21957309
TI  - CD8+ T cell escape mutations in simian immunodeficiency virus SIVmac239 cause
      fitness defects in vivo, and many revert after transmission.
AB  - Virus-specific CD8(+) T lymphocytes select for escape mutations in human
      immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). To assess
      the effects of these mutations on viral fitness, we introduced escape mutations
      into 30 epitopes (bound by five major histocompatibility complex class I [MHC-I]
      molecules) in three different viruses. Two of these MHC-I alleles are associated
      with elite control. Two of the three viruses demonstrated reduced fitness in
      vivo, and 27% of the introduced mutations reverted. These findings suggest that T
      cell epitope diversity may not be such a daunting problem for the development of
      an HIV vaccine.

PMID- 21957310
TI  - Retrofitting the genome: L1 extinction follows endogenous retroviral expansion in
      a group of muroid rodents.
AB  - Long interspersed nuclear element 1 (LINE-1; L1) retrotransposons are the most
      common retroelements in mammalian genomes. Unlike individual families of
      endogenous retroviruses (ERVs), they have remained active throughout the
      mammalian radiation and are responsible for most of the retroelement movement and
      much genome rearrangement within mammals. They can be viewed as occupying a
      substantial niche within mammalian genomes. Our previous demonstration that L1s
      and B1 short interspersed nuclear elements (SINEs) are inactive in a group of
      South American rodents led us to ask if other elements have amplified to fill the
      empty niche. We identified a novel and highly active family of ERVs (mysTR). To
      determine whether loss of L1 activity was correlated with expansion of mysTR, we
      examined mysTR activity in four South American rodent species that have lost L1
      and B1 activity and four sister species with active L1s. The copy number of
      recent mysTR insertions was extremely high, with an average of 4,200 copies per
      genome. High copy numbers exist in both L1-active and L1-extinct species, so the
      mysTR expansion appears to have preceded the loss of both SINE and L1 activity
      rather than to have filled an empty niche created by their loss. It may be
      coincidental that two unusual genomic events--loss of L1 activity and massive
      expansion of an ERV family--occur in the same group of mammals. Alternatively, it
      is possible that this large ERV expansion set the stage for L1 extinction.

PMID- 21957311
TI  - Glutamate excitotoxicity is involved in the induction of paralysis in mice after
      infection by a human coronavirus with a single point mutation in its spike
      protein.
AB  - Human coronaviruses (HCoV) are recognized respiratory pathogens, and some
      strains, including HCoV-OC43, can infect human neuronal and glial cells of the
      central nervous system (CNS) and activate neuroinflammatory mechanisms. Moreover,
      HCoV-OC43 is neuroinvasive, neurotropic, and neurovirulent in susceptible mice,
      where it induces chronic encephalitis. Herein, we show that a single point
      mutation in the viral spike (S) glycoprotein (Y241H), acquired during viral
      persistence in human neural cells, led to a hind-limb paralytic disease in
      infected mice. Inhibition of glutamate excitotoxicity using a 2-amino-3-(5-methyl
      3-oxo-1,2-oxazol-4-yl)propranoic acid (AMPA) receptor antagonist (GYKI-52466)
      improved clinical scores related to the paralysis and motor disabilities in S
      mutant virus-infected mice, as well as protected the CNS from neuronal
      dysfunctions, as illustrated by restoration of the phosphorylation state of
      neurofilaments. Expression of the glial glutamate transporter GLT-1, responsible
      for glutamate homeostasis, was downregulated following infection, and GYKI-52466
      also significantly restored its steady-state expression level. Finally, GYKI
      52466 treatment of S mutant virus-infected mice led to reduced microglial
      activation, which may lead to improvement in the regulation of CNS glutamate
      homeostasis. Taken together, our results strongly suggest an involvement of
      excitotoxicity in the paralysis-associated neuropathology induced by an HCoV-OC43
      mutant which harbors a single point mutation in its spike protein that is
      acquired upon persistent virus infection.

PMID- 21957312
TI  - Inhibitory effects of bile acids and synthetic farnesoid X receptor agonists on
      rotavirus replication.
AB  - Rotaviruses (group A rotaviruses) are the most important cause of severe
      gastroenteritis in infants and children worldwide. Currently, an antiviral drug
      is not available and information on therapeutic targets for antiviral development
      is limited for rotavirus infection. Previously, it was shown that lipid
      homeostasis is important in rotavirus replication. Since farnesoid X receptor
      (FXR) and its natural ligands bile acids (such as chenodeoxycholic acid [CDCA])
      play major roles in cholesterol and lipid homeostasis, we examined the effects of
      bile acids and synthetic FXR agonists on rotavirus replication in association
      with cellular lipid levels. In a mouse model of rotavirus infection, effects of
      oral administration of CDCA on fecal rotavirus shedding were investigated. The
      results demonstrate the following. First, the intracellular contents of
      triglycerides were significantly increased by rotavirus infection. Second, CDCA,
      deoxycholic acid (DCA), and other synthetic FXR agonists, such as GW4064,
      significantly reduced rotavirus replication in cell culture in a dose-dependent
      manner. The reduction of virus replication correlated positively with activation
      of the FXR pathway and reduction of cellular triglyceride contents (r(2) = 0.95).
      Third, oral administration of CDCA significantly reduced fecal virus shedding in
      mice (P < 0.05). We conclude that bile acids and FXR agonists play important
      roles in the suppression of rotavirus replication. The inhibition mechanism is
      proposed to be the downregulation of lipid synthesis induced by rotavirus
      infection.

PMID- 21957313
TI  - A genetic interaction between the core and NS3 proteins of hepatitis C virus is
      essential for production of infectious virus.
AB  - By analogy to other members of the Flaviviridae family, the hepatitis C virus
      (HCV) core protein is presumed to oligomerize to form the viral nucleocapsid,
      which encloses the single-stranded RNA genome. Core protein is directed to lipid
      droplets (LDs) by domain 2 (D2) of the protein, and this process is critical for
      virus production. Domain 1 (D1) of core is also important for infectious particle
      morphogenesis, although its precise contribution to this process is poorly
      understood. In this study, we mutated amino acids 64 to 75 within D1 of core and
      examined the ability of these mutants to produce infectious virus. We found that
      residues 64 to 66 are critical for generation of infectious progeny, whereas 67
      to 75 were dispensable for this process. Further investigation of the defective
      64 to 66 mutant (termed JFH1(T)-64-66) revealed it to be incapable of producing
      infectious intracellular virions, suggesting a fault during HCV assembly.
      Furthermore, isopycnic gradient analyses revealed that JFH1(T)-64-66 assembled
      dense intracellular species of core, presumably representing nucleocapsids. Thus,
      amino acids 64 to 66 are seemingly not involved in core
      oligomerization/nucleocapsid assembly. Passaging of JFH1(T)-64-66 led to the
      emergence of a single compensatory mutation (K1302R) within the helicase domain
      of NS3 that completely rescued its ability to produce infectious virus.
      Importantly, the same NS3 mutation abrogated virus production in the context of
      wild-type core protein. Together, our results suggest that residues 64 to 66 of
      core D1 form a highly specific interaction with the NS3 helicase that is
      essential for the generation of infectious HCV particles at a stage downstream of
      nucleocapsid assembly.

PMID- 21957314
TI  - Efficiency of neutralizing antibodies targeting the CD4-binding site: influence
      of conformational masking by the V2 loop in R5-tropic clade C simian-human
      immunodeficiency virus.
AB  - In R5-tropic clade C simian-human immunodeficiency viruses (SHIV-Cs), we
      identified a 3-asparagine (3N) deletion mutation in the V2 loop stem of gp120 as
      the major determinant of neutralization escape of the anti-CD4-binding site (anti
      CD4-bs) neutralizing monoclonal antibody (nMAb) b12. However, the more potent
      anti-CD4-bs nMAbs VRC01 and VRC03 were not sensitive to this mutation. Using
      isogenic tier 1 or tier 2 proviruses differing only in the 3N mutation, we showed
      that this mutation might result in selective conformational b12 epitope masking.
      Therefore, human immunodeficiency virus (HIV) Env immunogens targeting the CD4-bs
      and designed to neutralize tier 2 viruses should take conformational masking by
      the V2 loop into account.

PMID- 21957316
TI  - Teeth of the red fox Vulpes vulpes (L., 1758) as a bioindicator in studies on
      fluoride pollution.
AB  - An examination was made of fluoride content in the mandibular first molars of the
      permanent teeth of the red fox Vulpes vulpes living in north-west (NW) Poland.
      The teeth were first dried to a constant weight at 105 degrees C and then ashed.
      Fluorides were determined potentiometrically, and their concentrations were
      expressed in dry weight (DW) and ash. The results were used to perform an
      indirect estimation of fluoride pollution in the examined region of Poland. The
      collected specimens (n = 35) were classified into one of the three age
      categories: immature (im, 6-12 months), subadult (subad, from 12 to 20 months)
      and adult (ad, >20 months). The mean concentrations (geometric mean) of fluoride
      were similar in the im and subad groups (230 and 296 mg/kg DW and 297 and 385
      mg/kg ash, respectively), and significantly smaller than in the ad group (504 and
      654 mg/kg, respectively, in DW and ash). Basing on other reports that the ~400
      mg/kg DW concentration of fluoride in bones in the long-lived wild mammals
      generally reflects the geochemical background, it was found that 57% of the foxes
      in NW Poland exceeded this value by 9% to 170%. This indirectly reflects a
      moderate fluoride contamination in the tested region.

PMID- 21957317
TI  - Temporal and Spatial Dynamics of Carbon Fixation by Moso Bamboo (Phyllostachys
      pubescens) in Subtropical China.
AB  - To study the temporal and spatial dynamics of carbon fixation by Moso bamboo
      (Phyllostachys pubescens) in subtropical China, carbon fixation of leaves within
      the canopy of P. pubescens was measured with a LI-6400 portable photosynthesis
      system. The results showed that the capability of carbon fixation of P. pubescens
      leaves had obvious temporal and spatial dynamic variations. It was revealed that
      there were two peak periods and two low periods in the season variation of carbon
      fixation capability. Data also revealed that the capability of carbon fixation by
      five-year-old P. pubescens was more than that of one-year-old and three-year-old.
      Daily and seasonal carbon fixation showed a negative correlation with the CO(2)
      concentration. The temporal and spatial dynamics of carbon fixation by P.
      pubescens described above provided a scientific basis for development of
      technologies in bamboo timber production.

PMID- 21957315
TI  - DNA mismatch repair proteins are required for efficient herpes simplex virus 1
      replication.
AB  - Herpes simplex virus 1 (HSV-1) is a double-stranded DNA virus that replicates in
      the nucleus of its human host cell and is known to interact with many cellular
      DNA repair proteins. In this study, we examined the role of cellular mismatch
      repair (MMR) proteins in the virus life cycle. Both MSH2 and MLH1 are required
      for efficient replication of HSV-1 in normal human cells and are localized to
      viral replication compartments. In addition, a previously reported interaction
      between MSH6 and ICP8 was confirmed by coimmunoprecipitation and extended to show
      that UL12 is also present in this complex. We also report for the first time that
      MLH1 associates with ND10 nuclear bodies and that like other ND10 proteins, MLH1
      is recruited to the incoming genome. Knockdown of MLH1 inhibits immediate-early
      viral gene expression. MSH2, on the other hand, which is generally thought to
      play a role in mismatch repair at a step prior to that of MLH1, is not recruited
      to incoming genomes and appears to act at a later step in the viral life cycle.
      Silencing of MSH2 appears to inhibit early gene expression. Thus, both MLH1 and
      MSH2 are required but appear to participate in distinct events in the virus life
      cycle. The observation that MLH1 plays an earlier role in HSV-1 infection than
      does MSH2 is surprising and may indicate a novel function for MLH1 distinct from
      its known MSH2-dependent role in mismatch repair.

PMID- 21957318
TI  - Mark B. Brown, Science in Democracy. Expertise, Institutions, and Representation:
      MIT Press, Cambridge, MA., and London, 2009.

PMID- 21957320
TI  - Credit where credit's due: accounting for co-authorship in citation counts.
AB  - I propose a new method (Pareto weights) to objectively attribute citations to co
      authors. Previous methods either profess ignorance about the seniority of co
      authors (egalitarian weights) or are based in an ad hoc way on the order of
      authors (rank weights). Pareto weights are based on the respective citation
      records of the co-authors. Pareto weights are proportional to the probability of
      observing the number of citations obtained. Assuming a Pareto distribution, such
      weights can be computed with a simple, closed-form equation but require a few
      iterations and data on a scholar, her co-authors, and her co-authors' co-authors.
      The use of Pareto weights is illustrated with a group of prominent economists. In
      this case, Pareto weights are very different from rank weights. Pareto weights
      are more similar to egalitarian weights but can deviate up to a quarter in either
      direction (for reasons that are intuitive).

PMID- 21957319
TI  - The "Mendel syndrome" in science: durability of scientific literature and its
      effects on bibliometric analysis of individual scientists.
AB  - The obsolescence and "durability" of scientific literature have been important
      elements of debate during many years, especially regarding the proper calculation
      of bibliometric indicators. The effects of "delayed recognition" on impact
      indicators have importance and are of interest not only to bibliometricians but
      also among research managers and scientists themselves. It has been suggested
      that the "Mendel syndrome" is a potential drawback when assessing individual
      researchers through impact measures. If publications from particular researchers
      need more time than "normal" to be properly acknowledged by their colleagues, the
      impact of these researchers may be underestimated with common citation windows.
      In this paper, we answer the question whether the bibliometric indicators for
      scientists can be significantly affected by the Mendel syndrome. Applying a
      methodology developed previously for the classification of papers according to
      their durability (Costas et al., J Am Soc Inf Sci Technol 61(8):1564-1581, 2010a;
      J Am Soc Inf Sci Technol 61(2):329-339, 2010b), the scientific production of
      1,064 researchers working at the Spanish Council for Scientific Research (CSIC)
      in three different research areas has been analyzed. Cases of potential "Mendel
      syndrome" are rarely found among researchers and these cases do not significantly
      outperform the impact of researchers with a standard pattern of reception in
      their citations. The analysis of durability could be included as a parameter for
      the consideration of the citation windows used in the bibliometric analysis of
      individuals.

PMID- 21957321
TI  - A recursive field-normalized bibliometric performance indicator: an application
      to the field of library and information science.
AB  - Two commonly used ideas in the development of citation-based research performance
      indicators are the idea of normalizing citation counts based on a field
      classification scheme and the idea of recursive citation weighing (like in
      PageRank-inspired indicators). We combine these two ideas in a single indicator,
      referred to as the recursive mean normalized citation score indicator, and we
      study the validity of this indicator. Our empirical analysis shows that the
      proposed indicator is highly sensitive to the field classification scheme that is
      used. The indicator also has a strong tendency to reinforce biases caused by the
      classification scheme. Based on these observations, we advise against the use of
      indicators in which the idea of normalization based on a field classification
      scheme and the idea of recursive citation weighing are combined.

PMID- 21957322
TI  - Sources of avoidance motivation: Valence effects from physical effort and mental
      rotation.
AB  - When reaching goals, organisms must simultaneously meet the overarching goal of
      conserving energy. According to the law of least effort, organisms will select
      the means associated with the least effort. The mechanisms underlying this bias
      remain unknown. One hypothesis is that organisms come to avoid situations
      associated with unnecessary effort by generating a negative valence toward the
      stimuli associated with such situations. Accordingly, merely using a
      dysfunctional, 'slow' computer mouse causes participants to dislike ambient
      neutral images (Study 1). In Study 2, nonsense shapes were liked less when
      associated with effortful processing (135 degrees  of mental rotation) versus
      easier processing (45 degrees  of rotation). Complementing 'fluency' effects
      found in perceptuo-semantic research, valence emerged from action-related
      processing in a principled fashion. The findings imply that negative valence
      associations may underlie avoidance motivations, and have practical implications
      for educational/workplace contexts in which effort and positive affect are
      conducive to success.

PMID- 21957323
TI  - The Influence of Men's Income and Employment on Marriage and Cohabitation:
      Testing Oppenheimer's Theory in Europe.
AB  - This article discusses Oppenheimer's theory on marriage timing, reviews the way
      this theory was received in European demography and family sociology, and
      develops a new test of the theory using annual panel data from 13 European
      countries for the period 1994-2001. Several indicators of men's economic status
      are used, including school enrollment, employment, type of labor contract, work
      experience, income, and education. Effects of these indicators are estimated for
      the transition to marriage and cohabitation, as well as for the transition from
      cohabitation to marriage. Country differences in these effects are examined as
      well. The evidence provides strong support for the male breadwinner hypothesis on
      the one hand, and for Oppenheimer's career uncertainty hypothesis on the other.
      However, the relevance of these hypotheses also depends on the national context,
      and especially on the way gender roles are divided in a society.

PMID- 21957324
TI  - Ethnic Minority-Majority Unions in Estonia.
AB  - Ethnic minority-majority unions-also referred to as mixed ethnic unions-are often
      seen as the ultimate evidence of the integration of ethnic minorities into their
      host societies. We investigated minority-majority unions in Estonia, where ethnic
      minorities account for one-third of the total population (Russians 26%, followed
      by Ukrainians, Byelorussians, Finns and other smaller groups). Using data from
      the 2000 Estonian census and regression models, we found that Slavic women are
      less likely to be in minority-majority unions than are members of other minority
      groups, with Russians being the least likely. Finns, who are culturally most
      similar to the Estonian majority population, are the most likely to form a union
      with an Estonian. For ethnic minority women, the likelihood of being in minority
      majority unions is highest in rural areas and increases over generations, with
      third-generation immigrants being the most likely. Estonian women are most likely
      to have a minority partner when they or their parents were born abroad and when
      they live in urban areas. Our findings suggest that both the opportunity to meet
      potential partners and openness to other ethnic groups are important factors for
      understanding the dynamics of minority-majority unions.

PMID- 21957325
TI  - The Volunteer Satisfaction Index: A Validation Study in the Chinese Cultural
      Context.
AB  - Using a Hong Kong-sourced sample of 261 participants, this study set out to
      validate the Volunteer Satisfaction Index (VSI) in the Chinese cultural context
      and to evaluate its psychometric properties. The VSI was originally developed by
      Galindo-Kuhn and Guzley (2001) to measure the outcomes of volunteer experiences.
      In this study, exploratory factor analysis (EFA) yielded a different factor
      structure from that proposed by the scale developer. The three factors found were
      personal gain, relationship within organization and relationship with peers.
      Cronbach's alpha values were high for all three subscales. Results from
      correlation and regression analysis also confirmed the construct and criterion
      related validity of the scale. Thus, the reliability and validity of the scale
      were confirmed. Implications for the assessment of volunteer satisfaction and
      further directions for cross-cultural studies on related topics are discussed.

PMID- 21957326
TI  - Vacuolar organization in the nodule parenchyma is important for the functioning
      of pea root nodules.
AB  - Different models have been proposed to explain the operation of oxygen diffusion
      barrier in root nodules of leguminous plants. This barrier participates in
      protection of oxygen-sensitive nitrogenase, the key enzyme in nitrogen fixation,
      from inactivation. Details concerning structural and biochemical properties of
      the barrier are still lacking. Here, the properties of pea root nodule cortical
      cells were examined under normal conditions and after shoot removal. Microscopic
      observations, including neutral red staining and epifluorescence investigations,
      showed that the inner and outer nodule parenchyma cells exhibit different
      patterns of the central vacuole development. In opposition to the inner part, the
      outer parenchyma cells exhibited vacuolar shrinkage and formed cell wall
      infoldings. Shoot removal induced vacuolar shrinkage and formation of infoldings
      in the inner parenchyma and uninfected cells of the symbiotic tissue, as well. It
      is postulated that cells which possess shrinking vacuoles are sensitive to the
      external osmotic pressure. The cells can give an additional resistance to oxygen
      diffusion by release of water to the intercellular spaces.Immunolocalization
      studies proved higher expression of endo-beta-1,4-glucanases within expanding
      cells of the outer cortex of pea nodules comparing with nodule endodermis or
      nodule parenchyma, so it is suggested that (1) endo-glucanases are involved in
      growth related modifications of cell walls and (2) enlarged cells decrease nodule
      conductance to oxygen.

PMID- 21957327
TI  - Sex-specific effects of the local social environment on juvenile post-fledging
      dispersal in great tits.
AB  - An individual's decision to disperse from the natal habitat can affect its future
      fitness prospects. Especially in species with sex-biased dispersal, we expect the
      cost-benefit balance for dispersal to vary according to the social environment
      (e.g., local sex ratio and density). However, little is known about the social
      factors affecting dispersal decisions and about the temporal and spatial patterns
      of the dispersal process. In our study, we investigated experimentally the
      effects of the social environment on post-fledging dispersal of juvenile great
      tits by simultaneously manipulating the density and sex ratio of fledglings
      within forest plots. We expected young females in the post-fledging period mainly
      to compete for resources related to food and, as they are subordinate to males,
      we predicted higher female dispersal from male-biased plots. Juvenile males
      compete for vacant territories already in late summer and autumn; thus, we
      predicted increased male dispersal from high density and male-biased plots. We
      found that juvenile females had a higher probability to leave male-biased plots
      and had dispersed further from male-biased plots in the later post-fledging phase
      when juvenile males start to become territorial and more aggressive. Juvenile
      males were least likely to leave male-biased plots and had smallest dispersal
      distances from female-biased plots early after fledging. The results suggest that
      the social environment differentially affected the costs and benefits of
      philopatry for male and female juveniles. The local sex ratio of individuals is
      thus an important social trait to be considered for understanding sex-specific
      dispersal processes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of
      this article (doi:10.1007/s00265-011-1207-1) contains supplementary material,
      which is available to authorized users.

PMID- 21957329
TI  - Harvesting of microalgae by bio-flocculation.
AB  - The high-energy input for harvesting biomass makes current commercial microalgal
      biodiesel production economically unfeasible. A novel harvesting method is
      presented as a cost and energy efficient alternative: the bio-flocculation by
      using one flocculating microalga to concentrate the non-flocculating microalga of
      interest. Three flocculating microalgae, tested for harvesting of microalgae from
      different habitats, improved the sedimentation rate of the accompanying microalga
      and increased the recovery of biomass. The advantages of this method are that no
      addition of chemical flocculants is required and that similar cultivation
      conditions can be used for the flocculating microalgae as for the microalgae of
      interest that accumulate lipids. This method is as easy and effective as chemical
      flocculation which is applied at industrial scale, however in contrast it is
      sustainable and cost-effective as no costs are involved for pre-treatment of the
      biomass for oil extraction and for pre-treatment of the medium before it can be
      re-used.

PMID- 21957328
TI  - The interplay between gonadal steroids and immune defence in affecting a
      carotenoid-dependent trait.
AB  - The hypothesis that sexual ornaments are honest signals of quality because their
      expression is dependent on hormones with immune-depressive effects has received
      ambiguous support. The hypothesis might be correct for those signals that are
      carotenoid-dependent because the required carotenoid deposition in the signal,
      stimulated by testosterone, might lower the carotenoid-dependent immune defence
      of the organism. Two pathways underlying this androgen-dependent honest signaling
      have been suggested. Firstly, androgens that are needed for ornament expression
      may suppress immune defence, a cost that only high-quality animals can afford.
      Alternatively, immune activation may downregulate the production of androgens in
      low-quality individuals. Which of these alternatives is correct, and to what
      extent these effects are mediated by the different metabolites of androgens,
      remain open questions. To provide answers to these questions, we manipulated the
      levels of testosterone (T), 5alpha-dihydrotestosterone (DHT), and 17-beta
      estradiol (E2) in diamond doves Geopelia cuneata, a species in which both sexes
      exhibit a carotenoid-dependent, androgen-regulated red-orange periorbital ring of
      bare skin. On the first day of the experiment (day 0), we inserted steroid
      releasing implants into groups of birds and on day 14, we subjected half of the
      birds to an immunological challenge by immunizing them with sheep red blood cells
      (SRBC). In females, but not in males, androgen but not estradiol treatments
      reduced antibody production to SRBC. In addition, the immunological challenge
      reduced redness and size of the trait as well as androgens levels in both sexes
      and in all treatments. This indicates that an immunological challenge can lower
      circulating T at the cost of the trait expression. These findings are in
      accordance with both pathways postulated in the immunocompetence-handicap
      hypothesis, but do not entirely support the idea that the immunosuppressive
      effect of androgens yields honest signaling since both T and DHT were not
      immunosuppressive in males, for which sexual signaling is supposed to be
      especially important.

PMID- 21957330
TI  - Rapid Detection of Infestation of Apple Fruits by the Peach Fruit Moth, Carposina
      sasakii Matsumura, Larvae Using a 0.2-T Dedicated Magnetic Resonance Imaging
      Apparatus.
AB  - Infestation of harvested apple fruits by the peach fruit moth (Carposina sasakii
      Matsumura) was studied using a dedicated magnetic resonance imaging (MRI)
      apparatus equipped with a 0.2-T permanent magnet. Infested holes on the three
      dimensional (3-D) images tracked ecological movements of peach fruit moth larvae
      within the food fruits, and thus in their natural habitat. Sensitive short
      solenoid coil and surface coil detectors were devised to shorten measurement
      times. The short solenoid coil detected infestation holes at a rate of 6.4 s per
      image by the single-slice 2-D measurement. The multi-slice 2-D measurement
      provided six slice images of a fruit within 2 min taken by the two detectors.
      These results indicate that the 0.2-T MRI apparatus allows one to distinguish
      sound fruits from infested ones, and also as a means for plant protection and the
      preservation of natural ecological systems in foreign trade.

PMID- 21957333
TI  - The selection of experts evaluating health projects for the EU Sixth Framework
      Program.
AB  - AIM: The Framework Programmes for Research and Technological Development (FP) are
      the European Union's funding programmes for research in Europe. The study
      analyses the features of external experts involved in evaluating the research
      proposals in FP6 (years 2003-2006) in the area of Life Sciences.  SUBJECTS AND
      METHODS: Experts were analysed with respect to nationality, gender,
      organisational affiliation and rotation. The correlations between the number of
      experts by nationality and scientific research indicators were also explored. 
      RESULT: Experts from 70 countries participated, with 70% coming from 10
      countries. The gender composition was relatively stable, with approximately 30%
      of female experts. The majority of experts came from higher education
      establishments (51%) and 12% from industry. About 40% of experts participated in
      the evaluation process two or more times. The number of experts by nationality
      was linearly correlated with gross national income (r = 0.95, p < 0.0001),
      population (r = 0.91, p < 0.0001), and number of research publications in health
      sciences (r = 0.93, p < 0.0001). However, using multiple linear regression
      analysis, only gross national income had partial regression coefficients
      significantly different from zero (p = 0.017). The observed value of experts for
      Italy (312) and Belgium (155) were higher than predicted by this regression model
      (231 and 71 respectively).  CONCLUSION: The expert panels involved were balanced
      with respect to nationalities, whereas the gender distribution was lower than the
      target. There was a satisfactory degree of rotation of experts between evaluation
      rounds. The percentage of experts from industry was lower than expected.

PMID- 21957331
TI  - Free Radicals, Salicylic Acid and Mycotoxins in Asparagus After Inoculation with
      Fusarium proliferatum and F. oxysporum.
AB  - Electron paramagnetic resonance was used to monitor free radicals and
      paramagnetic species like Fe, Mn, Cu generation, stability and status in
      Asparagus officinalis infected by common pathogens Fusarium proliferatum and F.
      oxysporum. Occurrence of F. proliferatum and F. oxysporum, level of free radicals
      and other paramagnetic species, as well as salicylic acid and mycotoxins content
      in roots and stems of seedlings were estimated on the second and fourth week
      after inoculation. In the first term free and total salicylic acid contents were
      related to free radicals level in stem (P = 0.010 and P = 0.033, respectively).
      Concentration of Fe(3+) ions in porphyrin complexes (g = 2.3, g = 2.9) was
      related to the species of pathogen. There was no significant difference between
      Mn(2+) concentrations in stem samples; however, the level of free radicals in
      samples inoculated with F. proliferatum was significantly higher when compared to
      F. oxysporum.

PMID- 21957332
TI  - Implementation and impact of a meningococcal C conjugate vaccination program in
      13- to 25-year-old individuals in Galicia, Spain.
AB  - BACKGROUND: In response to increased case numbers of meningococcal group C
      disease, catch-up vaccination strategies have been shown to be successful. This
      paper describes the results of a repeat vaccination program in Galicia, Spain,
      and the strategy used for it.  METHODS AND RESULTS: Three vaccination waves were
      performed: first, in 1996/1997 with a meningococcal group A and C polysaccharide
      vaccine in individuals aged 18 months to 19 years; second, in 2000 with a
      conjugate serogroup C polysaccharide vaccine in children born since 1993 and all
      children and adolescents up to 19 years not previously vaccinated; third, a
      campaign in 2006 that became necessary because of the development of a new
      Neisseria strain and an increase in both the incidence and lethality of
      meningococcal C disease. The conjugate vaccine de-O-acetylated group C
      meningococcal polysaccharide coupled to tetanus toxoid was used (GCMP-TT; brand
      name, NeisVac-C). Results: Applying a strategy based on model calculations
      derived from the UK setting and focusing on a population aged 13-25 years,
      including students, employees of companies, and underage individuals, a total of
      286,000 subjects were vaccinated, resulting in global vaccination coverage of
      82.2% (all age groups over 74%). Only 17 adverse events in 17 individuals were
      reported, which all were mild. Incidence of meningococcal disease serogroup C by
      season was reduced from 0.84 cases per 100,000 in 2004/05 to 0.76 cases per
      100,000 in 2005/2006 to 0.18/100,000 in 2007/08. In parallel, mortality was also
      decreased from 8 cases during 2005/06 (0.29 per 100,000) to 1 case in 2007/2008
      (0.03 per 100,000). No cases of breakthrough disease occurred in the vaccinated
      population.  CONCLUSION: In Galicia, a series of vaccination campaigns,
      particularly focusing on high-risk groups, has shown high effectiveness, with a
      marked reduction in the disease incidence in the vaccination cohort accompanied
      by a relevant reduction in the overall population.

PMID- 21957334
TI  - Interpreting a genetic case-control finding: What can be said, what cannot be
      said and implications in Indian populations.
AB  - Identification of genetic variants responsible for complex disorders using
      association mapping is an active area of research. There are two broad classes of
      association methodologies: population-based case-control studies and family-based
      transmission analyses. While case-control analyses are more popular and in
      general, more powerful than family-based analyses, they suffer from some inherent
      limitations. Thus, it is of importance, to understand the implications of an
      association finding obtained from a case-control study design. This article
      discusses the relative advantages and disadvantages of the two classes of
      association analyses, particularly in the context of genetic diversity in Indian
      populations.

PMID- 21957335
TI  - Application of diagnostic methods and molecular diagnosis of hemoglobin disorders
      in Khuzestan province of Iran.
AB  - BACKGROUND: The hemoglobinopathies refer to a diverse group of inherited
      disorders characterized by a reduced synthesis of one or more globin chains
      (thalassemias) or the synthesis of structurally abnormal hemoglobin (Hb). The
      thalassemias often coexist with a variety of structural Hb variants giving rise
      to complex genotypes and an extremely wide spectrum of clinical and hematological
      phenotypes. Hematological and biochemical investigations and family studies
      provide essential clues to the different interactions and are fundamental to DNA
      diagnostics of the Hb disorders. Although DNA diagnostics have made a major
      impact on our understanding and detection of the hemoglobinopathies, DNA mutation
      testing should never be considered a shortcut or the test of first choice in the
      workup of a hemoglobinopathy. MATERIALS AND METHODS: A careful three-tier
      approach involving: (1) Full blood count (2) Special hematological tests,
      followed by (3) DNA mutation analysis, provides the most effective way in which
      to detect primary gene mutations as well as gene-gene interactions that can
      influence the overall phenotype. With the exception of a few rare deletions and
      rearrangements, the molecular lesions causing hemoglobinopathies are all
      identifiable by PCR-based techniques. Furthermore, each at-risk ethnic group has
      its own combination of common Hb variants and thalassemia mutations. In Iran,
      there are many different forms of alpha and beta thalassemia. Increasingly,
      different Hb variants are being detected and their effects per se or in
      combination with the thalassemias, provide additional diagnostic challenges.
      RESULTS: We did step-by-step diagnosis workup in 800 patients with
      hemoglobinopathies who referred to Research center of Thalassemia and
      Hemoglobinopathies in Shafa Hospital of Ahwaz Joundishapour University of medical
      sciences, respectively. We detected 173 patients as iron deficiency anemia (IDA)
      and 627 individuals as thalassemic patients by use of different indices. We have
      successfully detected 75% (472/627) of the beta-thalassemia mutations by using
      amplification refractory mutation system (ARMS) technique and 19% (130/627) of
      the beta-thalassemia mutations by using Gap-PCR technique and 6% (25/627) as Hb
      variants by Hb electrophoresis technique. We did prenatal diagnosis (PND) for 176
      couples which had background of thalassemia in first pregnancy. Result of PND
      diagnosis in the first trimester was 35% (62/176) affected fetus with beta
      thalassemia major and sickle cell disease that led to termination of the
      pregnancy. CONCLUSION: Almost all hemoglobinopathies can be detected with the
      current PCR-based assays with the exception of a few rare deletions. However, the
      molecular diagnostic service is still under development to try and meet the
      demands of the population it serves. In the short term, the current generation of
      instruments such as the capillary electrophoresis systems, has greatly simplified
      DNA sequence analysis.

PMID- 21957336
TI  - Evolution of phenylthiocarbamide taster trait in Mysore, South India.
AB  - BACKGROUND: The ability to taste phenylthiocarbamide (PTC), a bitter chemical has
      long been known to be a heritable trait, which is being widely used for both
      genetic and anthropological studies. The frequency of taster and non-taster
      allele is found to vary in different populations. AIMS AND OBJECTIVE: To
      investigate the frequency of taster trait in Mysore, South India. MATERIALS AND
      METHODS: The present investigation was conducted in Mysore, South India during
      2002 - 2003. About 3282 subjects irrespective of age, sex, religion, food habits,
      socio-economic status were randomly selected from various parts of the city and a
      total of 180 families, which included Christian (50), Hindu (61) and Muslim (69)
      were screened from different localities of the city. Harris and Kalmus method was
      used to assess the PTC taster and nontaster phenotype. RESULTS: It was found that
      tasters were significantly more frequent than nontasters in all the four
      categories. The incidence of tasters was more in unbiased category (85%) and less
      in Muslim category (58%). Investigations on PTC tasting in the families of three
      different religious groups revealed that the tasters were significantly more
      frequent than nontasters. It was also found that heterozygous father or mother
      for the taster genes with nontaster partner had taster and nontaster progenies in
      the ratio 1.0: 1.54 indicating the deviation in the segregation pattern of test
      cross. CONCLUSION: In Mysore, tasters are more frequent than nontasters.
      Variation in the frequency of nontaster allele in the religious groups could be
      due to inbreeding.

PMID- 21957337
TI  - A monozygotic twin pair with beta-thalassemia carrier status in a Dudh Kharia
      tribal family of Orissa.
AB  - BACKGROUND: The beta-thalassemia syndrome is a genetically inherited commonly
      encountered hematological disorder in the state of Orissa. It causes high degree
      of morbidity, mortality and fetal wastage in the poor vulnerable people. AIMS AND
      OBJECTIVES: There is an equal probability (50% chance) in every singleton
      pregnancy that a carrier parent of beta-thalassemia major would either bear
      normal or carrier offspring, but not two offspring with carrier of beta
      thalassemia major genotype together. For the first time, a carrier parent of beta
      thalassemia major gene has born progeny (three daughters and a twin male
      offspring) with a carrier status of beta-thalassemia major in Dudh Kharia tribal
      family studied from Sundargarh district of Orissa. MATERIALS AND METHODS: We
      screened randomly selected population of Dudh Kharia tribe from Sundargarh
      district of Orissa for hemoglobinopathies to assess the extent of the problem,
      design possible interventions and provide genetic counseling to them. A family
      with twin children was identified during screening in Lata Gaon in Bargaon block
      of Sundargarh district of Orissa for the above-mentioned study. Background
      information for this family such as name, age, sex, tribe, native place,
      reproductive history, family pedigree and clinical signs and symptoms were also
      recorded. Standardized genetic and hematological procedures and techniques were
      followed for analysis. RESULTS: Laboratory investigations for alkaline
      electrophoresis of blood lysate on cellulose acetate membrane showed raised
      hemoglobin A(2) level in mother (Hb A(2) = 5.3%), in three daughters (Hb A(2)
      =6.5, 5.9, 5.5% in chronological and birth order), in two twin sons (Hb A(2)
      =5.9% and 6.0%) and normal (Hb A(2) = 3.3%) for father. Hence, all the children
      i.e., three daughters and two twin sons, including the mother were beta
      thalassemia carriers. Since all the hematological parameters i.e., red cell
      indices, G-6-PD enzyme activity, ABO and Rhesus blood groups and identical beta
      thalassemia (trait) genotypes with identical clinical manifestations and
      hematological profile of the twin sons under similar environmental conditions,
      hence they were labeled as identical monozygotic twins. CONCLUSIONS: It is a rare
      occasion when a single pregnancy carries either one or two abnormal genotypes at
      a time in a womb in human beings. Monozygotic twins are genetically alike and
      provide appraisal of the expression of identical genotype under the different
      environmental conditions.

PMID- 21957338
TI  - Impact of pericentric inversion of Chromosome 9 [inv (9) (p11q12)] on
      infertility.
AB  - BACKGROUND: One of the frequent occurrences in chromosome rearrangements is
      pericentric inversion of the Chromosome 9; inv (9) (p11q12), which is consider to
      be the variant of normal karyotype. Although it seems not to correlate with
      abnormal phenotypes, there have been many controversial reports indicating that
      it may lead to abnormal clinical conditions such as infertility. The incidence is
      found to be about 1.98% in the general population. MATERIALS AND METHODS: We
      investigated the karyotypes of 300 infertile couples (600 individuals) being
      referred to our infertility clinic using standard GTG banding for karyotype
      preparation. RESULTS: The chromosomal analysis revealed a total of 15 (2.5%)
      inversions, among these, 14 male patients were inversion 9 carriers (4.69%) while
      one female patient was affected (0.33%). The incidence of inversion 9 in male
      patients is significantly higher than that of normal population and even than
      that of female patients (P< 0.05). CONCLUSIONS: This result suggests that
      inversion 9 may often cause infertility in men due to spermatogenic disturbances,
      which are arisen by the loops or acentric fragments formed in meiosis.

PMID- 21957339
TI  - Missense mutation G296S in GATA4 is not responsible for cardiac septal defects.
AB  - BACKGROUND: The most common type of congenital heart disease is the cardiac
      septal defects, which has reported to be caused by a missense mutation (G296S) in
      exon 3 of the GATA4 gene. AIMS: The present study was undertaken to find out
      whether GATA4 gene is the prime cause of the septal defects in Mysore population.
      MATERIALS AND METHODS: GATA4 gene analyses were undertaken on 21 confirmed CHD
      cases by PCR and DNA sequencing. RESULTS AND CONCLUSION: Analysis of this
      particular mutation in 21 septal defect patients revealed that none of the
      patients had the mutation, indicating that this mutation is population specific
      or septal defect in Mysore population is caused due to mutations in other regions
      of the GATA4 gene.

PMID- 21957340
TI  - Dandy-Walker malformations in a case of partial trisomy 9p (p12.1->pter) due to
      maternal translocation t(9;12)(p12.1;p13.3).
AB  - We describe a five-year-old proband presented with Dandy-Walker malformations,
      right microopthalmia, hamstring contractures, undescended testis with absence of
      testis in right scrotum in addition to typical trisomy 9p clinical features.
      Routine cytogenetic studies with GTG - banding showed 46,XY,der(12)t(9;12)
      (p12;q13.3),mat karyotype (trisomy 9p). Chromosomal analysis of the father was
      normal and phenotypically normal mother had 46,XX,t(9;12)(p12;q13) karyotype.
      Fluorescence in situ hybridization analysis with single copy probes bA5OIA2
      (9p11.2), bA562M8 (12p12.1) and centromere probes (9) showed break point at
      9p12.1 region. The gene dosage effect of Chromosome 9p along with environmental
      factors might be associated with Dandy- Walker malformations in the patient.

PMID- 21957341
TI  - Mutational spectrum of thalassemias in India.

PMID- 21957342
TI  - MTHFR gene polymorphisms analyzed in population from Kolkata, West Bengal.

PMID- 21957344
TI  - Genetically predisposed, life style and occurrence of metastatic cancer.

PMID- 21957343
TI  - Complement receptor 1 and the molecular pathogenesis of malaria.
AB  - Malaria is a pathogenic infection caused by protozoa of the genus plasmodium. It
      is mainly confined to sub-Saharan Africa, Asia and South America. This disease
      claims the life of over 1.5 to 2.7 million people per year. Owing to such a high
      incidence of malarial infections, there is an urgent need for the development of
      suitable vaccines. For the development of ideal vaccines, it is essential to
      understand the molecular mechanisms of malarial pathogenesis and the factors that
      lead to malaria infection. Genetic factors have been proposed to play an
      important role in malarial pathogenesis. Complement receptor 1 (CR1) is an
      important host red blood cell protein involved in interaction with malarial
      parasite. Various polymorphic forms of CR1 have been found to be involved in
      conferring protection or increasing susceptibility to malaria infections. Low
      density allele (L) of CR1 gave contradictory results in different set of studies.
      In addition, Knops polymorphic forms Sl (a(+)) and McC (a) have been found to
      contribute more towards the occurrence of cerebral malaria in malaria endemic
      regions compared to individuals with Sl (a(-)) / McC (a/b) genotype. This article
      reviews the research currently going on in this area and throws light on as yet
      unresolved mysteries of the role of CR1 in malarial pathogenesis.

PMID- 21957345
TI  - Genetic variation in exon 5 of troponin - I gene in hypertrophic cardiomyopathy
      cases.
AB  - BACKGROUND: Cardiomyopathies are a heterogeneous group of heart muscle disorders
      and are classified as 1) Hypertrophic Cardiomyopathy (HCM) 2) Dilated
      cardiomyopathy (DCM) 3) Restrictive cardiomyopathy (RCM) and 4) Arrhythmogenic
      right ventricular dysplasia (ARVD) as per WHO classification, of which HCM and
      DCM are common. HCM is a complex but relatively common form of inherited heart
      muscle disease with prevalence of 1 in 500 individuals and is commonly associated
      with sarcomeric gene mutations. Cardiac muscle troponin I (TNNI-3) is one such
      sarcomeric protein and is a subunit of the thin filament-associated troponin
      tropomyosin complex involved in calcium regulation of skeletal and cardiac muscle
      contraction. Mutations in this gene were found to be associated with a history of
      sudden cardiac death in HCM patients. AIM: Therefore the present study aims to
      identify for mutations associated with troponin I gene in a set of HCM patients
      from Indian population. MATERIALS AND METHODS: Mutational analyses of 92 HCM
      cases were carried out following PCR based SSCP analysis. RESULTS: The study
      revealed band pattern variation in 3 cases from a group of 92 HCM patients. This
      band pattern variation, on sequencing revealed base changes, one at nt 2560 with
      G>T transversion in exon-5 region with a wobble and others at nt 2479 and nt 2478
      with G>C and C>G transversions in the intronic region upstream of the exon 5 on
      sequencing. Further analysis showed that one of the probands showed apical form
      of hypertrophy, two others showing asymmetric septal hypertrophy. Two of these
      probands showed family history of the condition. CONCLUSIONS: Hence, the study
      supports earlier reports of involvement of TNNI-3 in the causation of apical and
      asymmetrical forms of hypertrophy.

PMID- 21957346
TI  - Dopamine receptor D4 exon 3 variable number of tandem repeat polymorphism:
      Distribution in eastern Indian population.
AB  - BACKGROUND: A 48bp variable number of tandem repeat (VNTR), in the dopamine
      receptor D4 (DRD4), has been extensively studied in association with a variety of
      traits and neuropsychiatric disorders in different ethnic groups; the VNTR has
      been found to affect receptor binding. AIMS: This investigation, for the first
      time, compared distribution of DRD4 VNTR in different Indian populations from the
      eastern part of the country, belonging to Indo-Caucasoid and Indo-Mongoloid
      ethnicity. MATERIALS AND METHODS: 852 individuals were recruited and divided into
      six population groups; Brahmin, Kayastha, Scheduled Caste, Mahishya, Muslim and
      Manipuri (Meitei). Allele and genotype frequencies were compared among groups as
      well as with data available for south-western Indian population. RESULTS: A total
      of six alleles (2-7-repeats) were observed, of which the 4-repeat (4R) was most
      frequent. Gross genetic dissimilarities were noticed between the Indo-Caucasoid
      and Indo-Mongoloid ethnic groups. Muslim group lacked 5R and 7R, while Manipuri
      group exhibited a very high frequency of 2R. Populations from eastern India
      revealed lower 7R frequencies as compared to the south-western populations.
      CONCLUSIONS: The DRD4 VNTR has been reported to play important role in cognition
      and alleles with higher repeats have been found to be associated with novelty
      seeking and personality traits. The present comparative analysis of different
      eastern Indian population would be helpful in extending our knowledge on this
      particular DRD4 variant. It will also be useful in understanding the behavioural
      differences between populations in the light of their genetic make up.

PMID- 21957347
TI  - Human sex ratio at birth in South West Nigeria.
AB  - BACKGROUND: Human sex ratio at birth differs from one population to the other.
      This variation has been attributed to cultural practices, seasonal variation,
      small-family size policy and sex selective technology. Information on secondary
      sex ratio in Nigeria is limited. AIMS AND OBJECTIVE: To analyzed human sex ratio
      at birth for samples of the Nigerian population in 4 urban settings in Southwest
      Nigeria, in order to know the trend and to compare the findings with those of
      previous reports. MATERIALS AND METHODS: Data were collected from Obafemi Awolowo
      University (OAU) teaching hospital at Ile Ife and Wesley Guild hospital at Ilesa,
      Osun state; General hospital at Ogbomoso, Oyo state and Ekiti state specialist
      hospital at Ado-Ekiti, Ekiti state. The data consisted of 35 209 live single
      births recorded between 1995 and 2004. Each set of data was analyzed to determine
      the sex ratio by year, month and quarterly values. Chi-square analysis was used
      to determine the deviation of the sex ratios for the years from the average
      value. RESULTS: The annual average ratios of 104.7:100, 102.8:100, 98.9:100 and
      100.8:100 were recorded for OAU teaching hospital, Wesley Guild Hospital, General
      Hospital and Ekiti State specialist hospital, respectively. When pooled together,
      the average ratio was 102.7:100. This shows some bias for male births. Data also
      indicates more male birth in the rainy season, suggesting a seasonal variation of
      sex ratio. CONCLUSION: These findings are representative of the populations in
      southwest Nigeria and are comparable to values obtained for other regions in
      Nigeria and other populations of African origin.

PMID- 21957348
TI  - Distribution profile of paraoxonase phenotypes among the Gujaratis.
AB  - BACKGROUND: Paraoxonase (PON1) can hydrolyze organophosphate pesticides (OP) and
      has a key role in the susceptibility of human in OP toxicity. The human-enzyme
      shows polymorphism and variations in the distribution profile of its phenotypes
      among different ethnic groups have been observed. AIMS: To see the distribution
      pattern of total PON1 activity in 45 healthy attendants of poisoning cases; 121
      healthy unrelated farm-labours and 59 normal subjects of trauma. MATERIALS AND
      METHODS: The PON1 activities from serum/plasma samples of these healthy normal
      individuals were estimated with/without addition of 1M NaCl in order to determine
      salt-stimulated and basal activity. The PON 1 phenotypes were determined on the
      basis of percent activation of enzyme activity. RESULTS: Tri-modal distribution
      of basal PON1 activity was observed among all these individuals. 52.0% of the
      individuals belonged to Phenotype A, 46.6% to phenotype AB while 1.4% to
      Phenotype B with gene frequency of allele-A and allele-B being 0.753 and 0.247
      respectively in excellent agreement with Hardy-Weinberg equilibrium. CONCLUSION:
      Maximum number of individuals belonged to phenotype-A (low PON1 activity) showing
      potential vulnerability towards Op-poisoning.

PMID- 21957349
TI  - Detection of Y STR markers of male fetal dna in maternal circulation.
AB  - BACKGROUND: Circulating fetal cells and cell free DNA in the maternal blood has
      been shown to help in prenatal diagnosis of genetic disorders without relying on
      invasive procedures leading to significant risk of pregnancy loss. AIM: The
      current study was undertaken to detect the male fetal population using Y STR
      markers DYS 19, DYS 385 and DYS 392 and also to study the extent of persistence
      of fetal DNA in the mother following delivery. MATERIALS AND METHODS: Blinded
      study was conducted on 50 mothers delivering male and female babies. Cellular and
      cell free DNA was extracted from maternal and fetal cord blood and amplified for
      Y STR markers by PCR. RESULTS: The amplification sensitivity of Y specific STR,
      DYS19 was 100% (22/22) in the male fetal DNA samples. The incidence of other
      STRs, i.e., DYS385 and DYS392 were 91% (20/22) each. Analysis of results revealed
      that thirteen of the twenty six women had detectable male fetal DNA at the time
      of delivery. However fetal DNA was not detectable twenty four hours after
      delivery. CONCLUSION: Preliminary results show that the separation of fetal cell
      free DNA in the maternal circulation is a good low-cost approach for the future
      development of novel strategies to provide non-invasive techniques for early
      prenatal diagnosis.

PMID- 21957350
TI  - Camptodactyly in Sotos syndrome.
AB  - We describe a girl with Sotos syndrome presenting at two and a half years age
      with developmental delay. She has camptodactyly which has not previously been
      reported in Sotos syndrome but is a common finding in Weaver syndrome. Both these
      conditions have been reported to have NSD1 gene mutations. This report is
      consistent with the conditions being allelic.

PMID- 21957351
TI  - Risk of Down syndrome conferred by MTHFR C677T polymorphism: Ethnic variations.

PMID- 21957352
TI  - Bombay phenotype in Orissa: What could we make out of it?

PMID- 21957353
TI  - Coagulation disorders seen through the window of molecular biology.
AB  - Coagulation disorders have been traditionally worked up by their clinical
      phenotypes and coagulation factor assays which are dependent on APTT- and PT
      based techniques. Development of chromogenic substrates in the late seventies and
      early eighties allowed coagulation factors to be measured like enzymes. There was
      still a major lacuna in the understanding of the biology of different coagulation
      disorders. Modern molecular biology - which developed as an unique synthesis of
      biochemistry, immunology, cell biology, and genetics - allowed us to have a more
      comprehensive understanding of the pathobiology of many of these coagulation
      disorders. This overview presents several examples which show how we have
      enriched our understanding about the varied clinical phenotypes of different
      coagulation disorders.

PMID- 21957354
TI  - DNA profiling: Social, legal, or biological parentage.
AB  - DNA profiling in forensic casework is based on comparison of the results of
      biological evidence with direct reference samples of the individual concerned or
      with indirect references of his close blood relatives. The selection of reference
      samples for analysis is crucial to the success of a case; it not only depends on
      the authenticity of the reference samples, but also on the authenticity of the
      biological relation of the donors with the person in question. There are
      situations when the social or legal relationship is not the biological one and
      there is a need to educate investigating officers, forensic analysts, and the
      judiciary about the associated problems.

PMID- 21957355
TI  - Can parallel mutation and neutral genome selection explain Eastern African M1
      consensus HVS-I motifs in Indian M haplogroups.

PMID- 21957356
TI  - PvuII polymorphism of estrogen receptor-alpha gene in breast cancer.
AB  - BACKGROUND: Estrogen receptor (ER) is a ligand-inducible transcription factor
      that mediates estrogen action in target tissue. Several common polymorphisms of
      the ERalpha gene have been reported to be associated with alterations in receptor
      expression in breast cancer. MATERIALS AND METHODS: A case-control study was
      designed to compare 250 breast cancer patients with 250 age-matched healthy
      controls. The frequency distribution of PvuII polymorphism in the ERalpha gene
      was assessed by PCR-RFLP method. RESULTS: The frequency of the PP genotype
      (35.3%) was increased significantly in breast cancer patients when compared to
      controls (19.8%), with a corresponding increase in P allele frequency (chi(2)=
      16.4; P = 0.0003). The OR for genotypes PP vs. Pp was 1.989 (95% CI: 1.2708 to
      3.113). Premenopausal women with breast cancer had an elevated frequency of the
      PP genotype (22.8%) as compared to postmenopausal women (16.8%). The frequency of
      the PP genotype was increased in patients positive for ER and HER-2/neu as
      compared to those with receptor-negative status. The pp and p allele frequencies
      were increased in progesterone-receptor-negative status. When stage of the
      disease was considered, both Pp and pp genotype frequencies were elevated in
      patients with advanced stage breast cancer. The frequency of the P allele and PP
      genotype frequencies tended to increase with increase in body mass index, whereas
      the Pp genotype frequency was elevated only in obese patients. The reverse was
      observed in the case of pp genotype frequency. CONCLUSION: The study thus
      highlighted the influence of ERalpha PvuII polymorphism on the development and
      progression of breast cancer.

PMID- 21957357
TI  - Possible risk factors for Down syndrome and sex chromosomal aneuploidy in Mysore,
      South India.
AB  - BACKGROUND: Down syndrome (DS) and sex chromosomal aneuploidy (SA) are common
      chromosomal anomalies causing congenital malformations and mental retardation in
      humans. The well-established risk factor, advanced maternal age, was not found in
      many of the DS and SA cases in India, while the other possible risk factors have
      not been well studied. In view of this, the present study has been made.
      MATERIALS AND METHODS: During the last 5 years, 150 clinically suspected DS and
      25 SA cases were referred to our laboratory for chromosome investigation from
      major hospitals of Mysore city. Chromosome preparations were made from these
      patients after informed consent was obtained. Well-spread G-banded metaphase
      plates were analyzed by automated LEICA KARYO software. Two hundred and 100
      randomly selected families belonging to different religions were used as controls
      for the DS and SA cases, respectively. Statistical analysis was carried out using
      logistic regression RESULTS: Out of the 150 cases of DS, 122 had free trisomy 21,
      two were mosaic trisomy 21, and one had translocation. Logistic regression of
      case-control study of DS children revealed that the odds ratio of uncle-niece
      marriages, or second cousin marriages, or parents lived in rural region, or
      exposure of the parents to chemicals, or parents education status, or habits
      (tobacco/ alcohol used) of father, or mother not undergone prenatal scanning, or
      mothers with previous abortions were significant when all the variables of that
      category were used one at a time. Exposure of the parents to chemicals, parents'
      educational status, habits (tobacco/alcohol use) of the father, mother not
      undergone prenatal scanning, and history of previous abortions were significant
      when all the variables of that category were used one at a time. Similarly,
      except for consanguinity, history of previous abortions, and mother not undergone
      prenatal scanning, all other factors showed significant odds ratios in SA cases.
      CONCLUSION: Besides the known risk factors, consanguinity, region (rural/urban)
      of residence of parents, exposure of parents to chemicals, educational status of
      parents, habits of father, prenatal scanning, and reproductive performance of
      mother are possible risk factors for chromosomal aneuploidy.

PMID- 21957358
TI  - Identification of a rare blood group, "Bombay (Oh) phenotype," in Bhuyan tribe of
      Northwestern Orissa, India.
AB  - BACKGROUND: Blood group serology plays a vital role in transfusion medicine. The
      Bombay (Oh) phenotype is characterized by the absence of A, B, and H antigens on
      red cells and occurs rarely, especially in tribal populations of India. AIMS AND
      OBJECTIVES: This is a field-based random population study in the Bhuyan tribal
      community. The study reports three cases of the rare Bombay (Oh) phenotype for
      the first time in the Bhuyan tribe of Sundargarh district in North-Western
      Orissa. MATERIALS AND METHODS: Taking informed consent, red blood cells of 836
      Bhuyan subjects were tested with three antisera, i.e., anti-A, anti-B, and anti-H
      (lectin) for forward reaction. Agglutinations of plasma with A, B, and O (H) red
      cells (reverse reaction) were also tested for the presence or absence of
      antibodies in the serum. Specialized tests like absorption-elution, titration of
      naturally occurring antibodies at different temperatures, inhibition of anti-H by
      O saliva secretor, and determination of secretor status were performed. RESULTS:
      Three cases of a rare blood group, Bombay (Oh) phenotype, (2 out of 244 Khandayat
      Bhuyan and 1 out of 379 Paudi Bhuyan from Hemgiri and Lahunipara blocks,
      respectively) in the Bhuyan tribe of Sundargarh district in North-Western Orissa
      were detected, giving an incidence of 1 in 122 in Khandayat Bhuyan and 1 in 379
      in Paudi Bhuyan, with an average of 1 in 278 among the Bhuyan tribal population.
      This incidence is high in comparison to earlier studies reported from India.
      CONCLUSIONS: The practice of tribal and territorial endogamy in a smaller
      effective populations (for example, there are only 3,521 individuals in Paudi
      Bhuyan) results in smaller marital distance and inbreeding, leading to increased
      homozygous expression of rare recessive genetic characters like the Bombay (Oh)
      phenotype. This study further testifies that the incidence is higher in those
      states of India where the consanguinity is a common practice.

PMID- 21957359
TI  - Emergence of an unrelated highly aberrant clone in an AML patient at relapse four
      months after peripheral blood stem cell transplantation.
AB  - We report a case of AML-M1 with 5q aberration at diagnosis. The patient was
      treated with high-dose chemotherapy (HDCT). After remission induction, he
      received allogenic peripheral blood stem cell transplantation (PBSCT) from an HLA
      match donor brother. The successive follow-up conventional cytogenetics
      investigations in remission after HDCT and PBSCT revealed cytogenetic remission.
      The most interesting observation in this case is that relapsed marrow revealed
      the emergence of an entirely new, highly aberrant, unrelated clone with unusual
      translocations t(6;17)(p23;p11.2),+8,der(8)dup inv(8)(q23qter),
      t(10;19)(q26;q13.3) 41/2 months after PBSCT. Our findings suggest the possibility
      of a mutagenic effect of HDCT and myeloablative intense chemotherapy before PBSCT
      that could have induced a genetic lesion in the recipient's genetically unstable
      stem cells in an environment of immunosuppression. The highly complex nature of
      the clone and the rapid clonal evolution indicates the possibility of selective
      pressure with proliferative advantage.

PMID- 21957360
TI  - Rett syndrome molecular diagnosis and implications in genetic counseling.
AB  - Rett syndrome is a rare genetic X-linked dominant disorder. This syndrome is the
      most frequent cause of mental retardation in girls. In the classical form of the
      disease, the presenting signs and the course of development are characteristic.
      However clinical diagnosis can be very difficult when the expression is not in
      the classical form. Mutations in MeCP2 are responsible for 80% of cases. When
      MeCP2 mutation is found in an index case, genetic counseling is similar to that
      in other X-linked dominant genetic diseases. However, mutations in this gene can
      cause a spectrum of atypical forms. On the other hand, other genetic conditions
      like translocations, sex chromosome numerical anomalies, and mutations in other
      genes can complicate genetic counseling in this syndrome. We present the first
      case of molecular diagnosis of Rett syndrome in Iran and discuss the recent
      developments in its genetic counseling.

PMID- 21957361
TI  - Mowat-Wilson syndrome in a Moroccan consanguineous family.
AB  - Mowat-Wilson syndrome is a mental retardation-multiple congenital anomaly
      syndrome characterized by a typical facies, developmental delay, epilepsy, and
      variable congenital malformations, including Hirschsprung disease, urogenital
      anomalies, congenital heart disease, and agenesis of the corpus callosum. This
      disorder is sporadic and is caused by heterozygous mutations or deletions of the
      ZFHX1B gene located in the 2q22 region. We report here the first Moroccan
      patient, born to consanguineous parents, with Mowat-Wilson syndrome, due to a de
      novo, unreported mutation of the ZFHX1B gene.

PMID- 21957362
TI  - Translocation t(2;14)(p13;q32) in a case of Ph+ acute lymphoblastic leukemia.

PMID- 21957363
TI  - Construction industry: More needs to be done.

PMID- 21957365
TI  - Lead exposure and hair lead level of workers in a lead refinery industry in Iran.
AB  - This study was carried out on the workers of a lead refinery industry and two
      control groups in Zanjan city in Iran. The scalp hair samples were collected from
      25 workers who were occupationally exposed to lead contamination as a case group
      and from 25 subjects among the staff of the same industry and 25 subjects among
      Zanjan citizens as the first and second control groups respectively. A flame
      atomic absorption spectrophotometer used to determine lead level in all of the
      samples. The age of all subjects in the three groups was matched. The mean
      concentrations of hair lead in the workers (case group), the staff (control
      groupA) and the citizens (control group B) were 131.7+/-93.4 ugr/gr, 21.1+/-13.2
      ugr/gr and 27.9+/-14.1 ugr/gr respectively. The mean concentration of hair lead
      in the case group was more than hair lead of normal range found in humans (0-30
      ugr/gr). The mean of hair lead level in the citizens who had used gas vehicles
      was statistically higher than who had not used it (36.9+/-12.2 ugr/gr vs. 16.6+/
      4.9 ugr/gr, P<0.001).

PMID- 21957364
TI  - Occupational cancers in leather tanning industries: A short review.
AB  - Work in leather tanning involves exposure to a wide range of chemicals. Some of
      these are carcinogens or suspected carcinogens. Increased risks for a number of
      cancers have been reported among the tannery workers. In the present review, a
      detailed account of lung cancer, testicular cancer, soft tissue sarcoma,
      pancreatic cancer, bladder cancer among tannery workers is mentioned.

PMID- 21957366
TI  - Working conditions and related neuropsychiatric problems among shoemakers in
      Turkey: Do child workers differ from others?
AB  - OBJECTIVE: In this cross-sectional study, we investigated working conditions and
      related neuropsychiatric problems of shoemakers, including child workers, working
      in poor conditions with high health risks. Clinical diagnosis was not the
      objective of this study. MATERIALS AND METHODS: We collected data from 318
      workers ranging from 8-66 years of age. We evaluated working conditions,
      neuropathy symptoms and signs; urinary 2,5-hexanedione was used to estimate
      hexane exposure. We used the Zung depression scale for adult shoemakers to
      evaluate depression. RESULTS: All workshops employed fewer than 10 workers with
      median daily work duration of 12h. Smoking and alcohol consumption were high
      among all workers including children. Peripheral neuropathy symptoms and signs
      were observed in 88 workers (27.8%) and it was related to alcohol consumption.
      Sixty-eight workers (47.9%) had depression and it was associated with daily work
      duration. CONCLUSION: Extremely poor, unhygienic, working conditions and a high
      prevalence of neuropsychiatric disorders were the main problems observed among
      shoemakers. A high number of child workers increased the scale of these observed
      problems.

PMID- 21957367
TI  - Environmental health survey in asbestos cement sheets manufacturing industry.
AB  - About 673 small-scale asbestos mining and milling facilities and 33 large - scale
      asbestos manufacturing plants, (17 asbestos-cement product manufacturing plants
      and 16 other than asbestos-cement product plants) are situated in India. The
      present study reveals the exposure of commercial asbestos (chrysotile) in the
      occupational as well as ambient air environment of the asbestos-cement (AC)
      sheets industry using membrane filter method of Bureau of Indian Standards (BIS).
      The fibre concentrations in 15 samples collected in the occupational environment
      at ingredient feeding site, sheet-producing site, fibre godown were 0.079, 0.057
      and 0.078 f/cc, respectively and in five samples from surrounding ambient air at
      factory gate resulted fibre concentration of 0.071 f/cc. All the samples have
      shown fibre concentration lower than the threshold limit values (TLVs) prescribed
      by BIS. Morphological analysis of samples, further under phase contrast and
      polarized microscopy indicates the presence of chrysotile asbestos, which acts as
      carcinogen as well as co-carcinogen. A clinical examination of exposed subjects
      reveals that there was no case of clubbing, crepitation, ronchi and dyspnea on
      exertion; however, obstruction and restriction were 10.9 per cent and 25 per cent
      in exposed subjects, respectively while in control there were 12 per cent and 28
      per cent, respectively. The study revealed that chrysotile asbestos is emitted in
      the occupational as well as ambient environment that may cause adverse health
      impact.

PMID- 21957368
TI  - A study on blood eosinophil level and ventilatory pulmonary function of the
      workers exposed to storage grain dust.
AB  - The workers engaged in storage grain handling are exposed to storage grain dust
      and suffer from different respiratory symptoms like, cough wheezing, chest
      tightness, eye and nasal irritations. It has been reported abroad and the present
      study results noted that the grain handlers have allergic symptoms like redness
      of eyes, itching, sneezing, skin rash, breathlessness and decrement of pulmonary
      function test values. According to their nature of job, the workers of storage
      grain godowns were divided into four categories i.e., load handling worker (LHW),
      ancillary, quality control and depot administration workers. The pulmonary
      function tests (PFT) and the differential count of leucocytes were carried out
      among the workers by standard technique. Decrement of pulmonary function test
      values was noted with the increment of blood eosinophil level.The PFT results
      were presented according to the blood eosinophil level. The decrement of mean PFT
      values were noticed as the blood level of eosinophil gradually increased from, up
      to -4%, >4-10% and above 10%. The maximum numbers of workers in different job
      categories are belonged to >4 -10% of eosinophil level. The percentage figure of
      workers in different departments were LHW 48.38%, (n=45), ancillary 38.88%,
      (n=7), quality control 54.54% (n=6) and depot administration workers 47.05%
      (n=16) are belonged to that range. Among the total workers the higher figure was
      found >4-10% ranges 47.43% (n=74) workers. The allergic manifestations like
      redness, itchiness and watering of eyes, sneezing, cough, breathless etc. are
      reported. These workers have blood eosinophil level and low pulmonary function
      test values. The respiratory impairments among the workers are restrictive,
      obstructive and combined restrictive and obstructive type.

PMID- 21957369
TI  - Respiratory effects due to occupational exposure to formaldehyde: Systematic
      review with meta-analysis.
AB  - Subjects exposed to organic solvents frequently complain of respiratory symptoms.
      Epidemiological studies conducted in these exposed subjects with special
      reference to respiratory effects are very few and that too are on very small
      number of subjects. This paper critically reviews most of the epidemiological
      studies in formaldehyde induced respiratory effects and combines them through
      meta analysis to get global precise estimates of the respiratory risks.A
      computerized bibliographic search revealed 16 epidemiological studies out of
      which 12 studies were considered for meta analysis. The symptoms of upper
      respiratory tract were more prevalent as the combined odds of exposed was 5.04
      compared to controls. The pooled odds ratio for acute lower respiratory symptoms
      ranged between 1.85 and 2.91. The mean fall of FVC, FEV1 and FEV1/FVC was only
      3.4%, 3.6% and 0.6% respectively, which was not statistically or physiologically
      considered significant.

PMID- 21957370
TI  - Musculoskeletal problems among workers of an Iranian communication company.
AB  - INTRODUCTION: Work-related musculoskeletal disorders (WMSDs) are a common health
      problem throughout the world and a major cause of disability in the workplace.
      Awkward working posture is a main risk factor for developing WMSDs. Assessment of
      exposure level to WMSDs risks can be an appropriate base for planning and
      implementing interventional ergonomics program in the workplace. This study was
      conducted among workers of an Iranian communication company with the objectives
      of a) determination of WMSDs prevalence and b) assessment of exposure level to
      WMSDs risks. MATERIALS AND METHODS: In this cross-sectional study, 85 randomly
      selected workers from assembly line and closed circuit TV (CCTV) participated.
      Nordic musculoskeletal questionnaire (NMQ) was used to study prevalence of WMSDs
      and rapid upper limb assessment (RULA) technique was applied to assess physical
      exposure to the risks. RESULTS: The results of NMQ revealed that WMSDs occurred
      at an high rate. The highest rates of WMSDs prevalence were reported in shoulders
      (73%), knees (67.1%) and back (66.7%). RULA showed that the Grand Score of 88.1%
      of cases were high and very high (action levels 3 and 4). Significant association
      was found between risk level and musculoskeletal symptoms in lower back (P <
      0.05). CONCLUSION: Given the association between RULA score and the prevalence of
      the problems, reducing RULA score by designing ergonomic workstation may reduce
      the prevalence of WMSDs among the workers.

PMID- 21957372
TI  - Prevention and control of silicosis: A national challenge.

PMID- 21957371
TI  - A multicentric case-control study on the impact of air pollution on eyes in a
      metropolitan city of India.
AB  - PURPOSE: To study the effect of exposure to high level of air pollution on ocular
      surface health. MATERIALS AND METHODS: A total of 520 subjects volunteered to
      participate in this study. All volunteers were required to give a detailed
      history and were subjected to ophthalmic examination under slit lamp, visual
      acuity test, tear film break-up time (BUT) and Schrimer's test. RESULTS:
      Significantly high number of subjects in study group complained of ophthalmic
      symptoms compared to control group. Sevent eight per cent subjects in the study
      group had symptoms such as redness, watering, irritation, strain or photophobia
      whereas this number was 45% in control group. Schirmer's test showed a
      significantly low value of 22.75+/-8.91 mm in study group as compared to 30.30+/
      7.92 mm in control group (P<0.001). Average tear break-up time in study group was
      significantly low (P<0.05) with a value of 11.17+/-2.92 seconds compared to 12.13
      +/- 3.24 seconds in control group. CONCLUSION: Results of our study indicate that
      people traveling in highly polluted areas and exposed to high level of air
      pollutants are likely to suffer from significantly high incidence of subclinical
      ocular surface disorders.

PMID- 21957373
TI  - Vanadium pentoxide inhalation.
AB  - CONTEXT: This mini-review describes the toxic effects of vanadium pentoxide
      inhalation principally in the workplace and associated complications with
      breathing and respiration. Although there are some material safety data sheets
      available detailing the handling, hazards and toxicity of vanadium pentoxide,
      there are only two reviews listed in PubMed detailing its toxicity. AIM: To
      collate information on the consequences of occupational inhalation exposure of
      vanadium pentoxide on physiological function and wellbeing. MATERIALS AND
      METHODS: The criteria used in the current mini-review for selecting articles were
      adopted from proposed criteria in The International Classification of
      Functioning, Disability and Health. Articles were classified from an acute and
      chronic exposure and toxicity thrust. RESULTS: The lungs are the principal route
      through which vanadium pentoxide enters the body. It can injure the lungs and
      bronchial airways possibly involving acute chemical pneumonotis, pulmonary edema
      and/or acute tracheobronchitis. It may adversely influence cardiac autonomic
      function. It stimulates the secretion of cytokines and chemokines by hepatocytes
      and disrupts mitochondria function. It disrupts the permeability of the
      epithelium and promotes access of inflammatory mediators to the underlying
      neuronal tissue causing injury and neuronal death. When renal brush border
      membrane vesicles are exposed to vanadium pentoxide, there is a time-dependent
      inhibition of citrate uptake and Na(+) K(+) ATPase in the membrane possibly
      contributing to nephrotoxicity. Exposure results in necrosis of spermatogonium,
      spermatocytes and Sertoli cells contributing to male infertility. CONCLUSION:
      Vanadium pentoxide certainly has adverse effects on the health and the well-being
      and measures need to be taken to prevent hazardous exposure of the like.

PMID- 21957374
TI  - Occupational injury surveillance: A study in a metal smelting industry.
AB  - An investigation of occupational injury was undertaken in a metal smelting
      industry to examine the occurrence and nature of occupational accidents where
      analysis of occupational injury records was carried out. At the same time, all
      the workers were interviewed to collect data in relation to personal and
      occupational characteristics. With this information, the study aimed to examine
      the role of different factors in the causation of occupational accidents. High
      incidence of superficial injuries of limbs due mostly to stepping / striking
      against objects and overexertion / wrong movements of the workers and the
      frequent association of handling of small tools with work injuries, observed in
      this study indicated the role of human error in these accidents and highlighted
      the necessity of proper safety training of the workers. This study also
      highlighted the need of elevated safety status during summer months and in
      evening and night shifts (more so in the second half). Moreover, this study could
      categorize some high-risk groups e.g. young workers, less-experienced workers,
      obese workers, workers having smoking / chewing habits etc, who need special
      attention so far as workplace safety is concerned.

PMID- 21957375
TI  - Do bullae and emphysema increase risk of pneumothorax in silicosis?
AB  - BACKGROUND: The occurrence of occupational lung diseases is decreasing due to
      improvements in occupational health in recent years; however, silicosis and its
      complications remain important occupational health problems. We have studied the
      role of emphysema and bullae as predictive factors of secondary spontaneous
      pneumothorax in acute and accelerated silicosis. MATERIALS AND METHODS: This
      study was carried out using questionnaire items on occupational history and
      conventional computed tomography of lungs. Differences between two groups
      (silicosis with and without secondary spontaneous pneumothorax) in terms of age,
      interval of exposure-diagnosis and therefore silica exposure duration were
      assessed by independentt -test. Fisher's exact test was used to determine the
      association between secondary spontaneous pneumothorax and both emphysema and
      bullae. RESULTS: We found a significant association between secondary spontaneous
      pneumothorax and bullae in acute and accelerated silicosis. CONCLUSION:
      Pneumothorax in silicosis could be attributed to previous bullae.

PMID- 21957376
TI  - Climate change: The challenges for public health preparedness and response- An
      Indian case study.
AB  - Extremes weather changes surpassing their usual statistical ranges and tumbling
      records in India could be an early warning bell of global warming. Extreme
      weather events like the recent record setting in western Indian city of Mumbai or
      all time high fatalities due to the heat wave in southern Indian states or
      increasing vulnerability of easten Indian states to flood could all be a
      manifestation of climate change in the Asian subcontinent. While the skeptics may
      be inclined to dismiss these events as simple local aberrations, when viewed in
      an epidemiological paradigm in terms of person, time and space couple with
      frequency, intensity and fatalities, it could well be an early manifestation of
      climate change. Global warming poses serious challenge to the health sector and
      hence warrants emergency health preparedness and response. Climate-sensitive
      diseases are among the largest global killers, hence major brunt of global
      climate change in terms of adverse health impact will be mostly borne by poor and
      developing countries in Asia, given the levels of poverty, nutional levels and
      poor public health infrastructure.

PMID- 21957377
TI  - E-waste management in India: An emerging environmental and health issue.

PMID- 21957378
TI  - Bitter sweet ?

PMID- 21957379
TI  - Denture labeling: A new approach.
AB  - The need for denture labeling is important for forensic and social reasons in
      case patients need to be identified individually. The importance of denture
      marking has long been acknowledged by the dental profession. Over the years,
      various denture marking systems have been reported in the literature, but none
      till date fulfills all the prescribed ADA specifications. A simple, easy,
      inexpensive procedure for marking accurate identification marks on dentures with
      a lead foil is described here. The label caring the patient information is
      incorporated in the acrylic resin during the denture processing.

PMID- 21957380
TI  - Comparative evaluation of hand and power-driven instruments on root surface
      characteristics: A scanning electron microscopy study.
AB  - AIM: The aim of this study was to compare root surface characteristics following
      root planing with various hand- and power-driven instruments. MATERIALS AND
      METHODS: A total of 20 single, rooted teeth were used in this study; two
      specimens were used as control (no instrumentation done) and the remaining 18
      specimens were equally divided into three groups. Specimens from each group were
      then subjected to root planing by one of the following instruments: (1) a Gracey
      curette, (2) ultrasonic tip and (3) a Rotary bur. In each case, the time required
      for scaling and root planing and surface roughness using the Roughness and Loss
      of Tooth Substance Index (RLTSI) was measured. RESULT: The mean RLTSI scores for
      the Gracey curette, ultrasonic and rotary instrument groups were 2.5, 2.0 and
      0.667, respectively. The mean scores of time spent for scaling and root planing
      by the Gracey curette, ultrasonic and rotary instrument groups in seconds were
      42.50, 35.83 and 54.50, respectively. CONCLUSIONS: All the three instruments,
      namely Gracey curette, ultrasonic tip and rotary bur, were effective in
      mechanical debridement of the root surface. The results favored the use of rotary
      instruments for root planing to achieve a smooth, clean root surface; however,
      the use of rotary instrument was more time consuming, which might limit its use
      in clinical practice.

PMID- 21957381
TI  - Editorial policy in reporting ethical processes: A survey of 'instructions for
      authors' in International Indexed Dental Journals.
AB  - BACKGROUND: The International Committee of Medical Journal Editors expects
      authors to report if their studies were carried out in accordance with the
      International Ethical Guidelines and Declaration of Helsinki; and inform readers
      regarding the same. AIMS: To determine the proportion of International Indexed
      Dental Journals reporting on ethical clearance for human and animal research,
      obtaining of informed consent and / or assent, and the conduction of research in
      accordance with the Declaration of Helsinki and International Medical Research,
      2006. SETTINGS AND DESIGN: A cross-sectional survey of 'instructions for
      authors,' for analysis of editorial policy on ethical processes, was done.
      MATERIALS AND METHODS: One hundred and twenty-six dental journals (which included
      50 general and 76 specialties) were reviewed for reporting, with regard to the
      Ethical Committee Approval for human and animal researches, obtaining of informed
      consent / assent from the research participants, and research in accordance with
      the Declaration of Helsinki as well as International Medical Research 2006 were
      analyzed. STATISTICAL ANALYSIS USED: Descriptive statistics was used and results
      were expressed in percentages. RESULTS: Of the 126 dental journals, 57 (45.23%)
      reported having obtained approval from the Ethics Committee, 33 (26.19%) were
      instructed about the Animal Ethics Committee approval, and 38 (30.15%) insisted
      on obtaining and reporting informed consent / assent. 41 (32.53%) journals
      expected authors to mention the research being conducted according to Declaration
      of Helsinki and and 3 (2.38%) journals required researches to be conducted in
      accordance with International Medical Research, 2006. CONCLUSIONS: A significant
      proportion of international indexed dental journals did not provide instructions
      to authors to report on the ethical approval, informed consent and / assent, and
      research conduction according to the Declaration of Helsinki as well as the
      International Medical Research, 2006.

PMID- 21957382
TI  - The relationship between maternal periodontitis and preterm low birth weight: A
      case-control study.
AB  - BACKGROUND: The relationship between periodontal diseases in pregnancy and
      children born prematurely or with low birth weight has been increasingly
      investigated, showing positive and negative results, respectively. OBJECTIVE: To
      evaluate the association between Maternal Periodontitis and Preterm delivery or
      Low Birth Weight. MATERIALS AND METHODS: In this case-control study, 104 pregnant
      women without systemic disease or other risk factors for preterm labor were
      chosen. The control group (n = 52) had term labor (infants >=37 weeks) and the
      case group (n = 52) had preterm labor (infants <37 weeks). Plaque index, bleeding
      index, and birth weight were measured. RESULTS: The data of plaque index (cases
      1.21+/-0.56; controls 0.63+/-0.31), bleeding index (cases, 2.08+/-0.62; controls,
      1.52+/-0.61), birth weight (cases, 2.01+/-0.36; controls 2.87+/-0.32), and
      Probing Pocket Depth (PPD) >=4mm and Clinical Attachment Level (CAL) >=3mm in at
      least 4 teeth (odds ratio 137.50, P value < 0.0001) revealed a statistically
      significant difference between the two groups P< 0.05). CONCLUSIONS: A noticeable
      relationship between periodontal health and duration of pregnancy; periodontal
      disease could be a risk factor for preterm labor. Oral hygiene maintenance should
      be a part of prenatal care protocol.

PMID- 21957383
TI  - Comparative evaluation of bond strength of three contemporary self-etch
      adhesives: An ex vivo study.
AB  - AIM: This study evaluated the effect of 2-hydroxymethyl methacrylate (HEMA) and
      the type of solvent on the tensile bond strength of the following three self-etch
      adhesives: Adper easy one (HEMA-rich adhesive) which contained ethanol, G-Bond
      (HEMA-free adhesive) which contained acetone, and Xeno V (HEMA-free adhesive)
      which contained butanol as a solvent. MATERIAL AND METHODS: Intact mandibular
      molars were mounted in self-cured resin and the occlusal surfaces were ground
      with # 600 SiC paper. Adhesives were applied on the prepared dentinal surfaces
      and the resin composite was condensed in the split brass mold (5 * 3 mm) placed
      over the adhesive surface. The specimens were stored in normal saline and placed
      in incubator at 37 degrees C. After 24 hours, the specimens were tested in
      tensile mode at a crosshead speed of 1 mm/min. Statistical analysis was done
      using One way ANOVA and Tukey's HSD test. RESULTS: The mean bond strengths of
      Adper easy one, G-Bond, and Xeno V were 12.41 MPa, 10.09 MPa, and 8.67 MPa,
      respectively. CONCLUSIONS: Comparison of contemporary adhesives in this ex vivo
      study revealed that the ethanol-based HEMA-rich self-etch adhesive is better than
      HEMA-free self-etch adhesive that contained acetone and butanol as the solvents,
      when compared in terms of bond strength.

PMID- 21957384
TI  - The effect of early childhood caries on the quality of life of children and their
      parents.
AB  - OBJECTIVE: To determine the effect the early childhood caries (ECC) has on
      quality of life (QOL) parameters of both children and their parents. MATERIALS
      AND METHODS: A cross-sectional study was carried out in the Department of
      Pedodontics and Preventive Dentistry, Manipal College of Dental Sciences,
      Manipal, India. CLINICAL SETTING: The study consisted of 500 children-parent
      pairs. The study was performed in Manipal and Bhubaneswar (250 children-parent
      pairs in each group), fulfilling the inclusion requirements of healthy children
      aged between 3 and 6 years old and children having ECC. The two groups were
      equally divided as follows: Group I - 250 child-parent pairs (Bhubaneswar) and
      Group II - 250 child-parent pairs (Manipal and Udupi). INTERVENTIONS: This was a
      questionnaire-based study and the parents and their children were provided the
      questionnaires with various questions on QOL parameters. Questionnaires were
      validated in the respective local languages. RESULTS: The data collected were
      analyzed using the SPSS (version 10.0) package. For assessing the internal
      consistency of the questionnaire, Cronbach's alfa test was used. To find the
      comparison between groups, Chi square test and "t" test were used. CONCLUSIONS:
      Oral health has a definite effect on the QOL of children. The most affected
      parameters by ECC were consumption of food and sleep in children, which
      significantly influence the parents. The questionnaire had good internal
      consistency in both Kannada and Oriya versions.

PMID- 21957385
TI  - Recurrent oral angioleiomyoma.
AB  - Angioleiomyomas are vascular variant of leiomyomas which are benign tumors of
      smooth muscle. They are exceedingly rare in the oral cavity. Malignant
      transformation of these tumors has also been reported occasionally which warrants
      knowledge of this soft tissue tumor. A 57 year old male patient reported with a
      15 day history of an asymptomatic growth that had started insidiously in his
      lower left back tooth region. Clinical examination revealed a solitary, oval,
      sessile growth in the mandibular left retro molar region. Excisional biopsy was
      suggestive of Angioleiomyoma. A recurrence of the same was noted two months later
      which was also histopathologically reported as Angioleiomyoma. The same was
      confirmed using special stains. This case reports an unusual presentation of
      Angioleiomyoma with regards to both recurrence as well as rapid growth. It is
      important to be well aware of this uncommon entity as these tumors often can
      mimic or transform into malignancy. Precise clinicopathological examinations are
      therefore invaluable in establishing an accurate diagnosis and delivering
      suitable treatment.

PMID- 21957386
TI  - Neoplastic potential of odontogenic cysts.
AB  - Odontogenic cysts and tumors are distinct entities and quite a common occurrence
      in the jaw bones. The lining of odontogenic cysts shows a potential for
      neoplastic transformation to non odontogenic malignancies like squamous cell
      carcinoma and mucoepidermoid carcinoma, and odontogenic tumors like ameloblastoma
      and adenoamatoid odontogenic tumor (AOT). AOT is a benign, epithelial odontogenic
      tumor, common site being the anterior maxilla. Its origin from a dentigerous cyst
      and in the mandible is rare. A case of an AOT arising from a dentigerous cyst
      associated with an impacted permanent mandibular left lateral incisor is
      reported.

PMID- 21957387
TI  - Bridge flap technique as a single-step solution to mucogingival problems: A case
      series.
AB  - Shallow vestibule, gingival recession, inadequate width of attached gingiva (AG)
      and aberrant frenum pull are an array of mucogingival problems for which several
      independent and effective surgical solutions are reported in the literature. This
      case series reports the effectiveness of the bridge flap technique as a single
      step surgical entity for increasing the depth of the vestibule, root coverage,
      increasing the width of the AG and solving the problem of abnormal frenum pull.
      Eight patients with 18 teeth altogether having Millers class I, II or III
      recession along with problems of shallow vestibule, inadequate width of AG and
      with or without frenum pull underwent this surgical procedure and were followed
      up till 9 months post-operatively. The mean root coverage obtained was 55% and
      the mean average gain in width of the AG was 3.5 mm. The mean percentage gain in
      clinical attachment level was 41%. The bridge flap technique can be an effective
      single-step solution for the aforementioned mucogingival problems if present
      simultaneously in any case, and offers considerable advantages over other
      mucogingival surgical techniques in terms of simplicity, limited chair-time for
      the patient and the operator, single surgical intervention for manifold
      mucogingival problems and low morbidity because of the absence of palatal donor
      tissue.

PMID- 21957388
TI  - Resolving mandibular arch discrepancy through utilization of leeway space.
AB  - Space management through utilization of leeway space represents one of the most
      critical aspects of interceptive orthodontic treatment in mixed dentition based
      on its potential to prevent crowding in the permanent dentition. Lingual arch is
      the most frequently used space maintaining device for preserving leeway. Case
      reports of patients in whom potential space discrepancy in mandibular arch was
      managed through preservation and utilization of leeway space are presented.

PMID- 21957389
TI  - Rhinomaxillary mucormycosis: A palatal ulcer.
AB  - Rhinocerebral mucormycosis (zygomycosis) is an opportunistic fungal infection
      caused by saprophytic fungus. It involves several areas of the body, but the
      rhinocerebral form is most relevant to health care providers. Zygomycosis is
      associated with medically compromised patients. Our case reports an unhealed
      ulcer present over the palate of 15 days duration associated with swelling over
      the maxillary sinus region. This case is a blend of clinical, radiological, and
      histological manifestations of mucormycosis in a patient.

PMID- 21957390
TI  - Variations in impacted mandibular permanent molars: Report of three rare cases.
AB  - The impaction of permanent teeth is not uncommon, but few permanent teeth are
      rarely impacted like mandibular first and second molars. Though third molars are
      commonly impacted, inversely impacted mandibular third molars are very rare.
      Here, we report three unusual cases of impacted mandibular molars accidentally
      diagnosed on conventional radiographs.

PMID- 21957392
TI  - Non-familial cherubism.
AB  - Cherubism is a rare, self-limiting, non-neoplastic fibro-osseous disorder of the
      jaws, usually seen in pediatric population. It is characterized by painless
      bilateral swelling of the jaws that gives the patient a typical cherubic
      appearance. Here, we describe the clinical, radiographic, histologic and computed
      tomographic features of cherubism in a 6-year-old boy.

PMID- 21957391
TI  - Unusual occurrence of accessory central cusp in the maxillary second primary
      molar.
AB  - Accessory cusp present on the occlusal surface may seldom pose problems. While
      its presence may not be a cause for alarm in most instances, it can sometimes
      lead to serious consequences if it is damaged. This case presents a rare finding
      of unilateral central accessory cusp seen on the occlusal surface of the
      maxillary left second primary molar and discusses the need for continuous dental
      surveillance and preventive measures.

PMID- 21957393
TI  - Pemphigus vulgaris.
AB  - Pemphigus vulgaris is a chronic autoimmune mucocutaneous disease that initially
      manifests in the form of intraoral lesions, which spread to other mucous
      membranes and the skin. The etiology of pemphigus vulgaris is still unknown,
      although the disease has attracted considerable interest. The pemphigus group of
      disease is characterized by the production of autoantibodies against
      intercellular substances and is thus classified as autoimmune diseases. Most
      patients are initially misdiagnosed and improperly treated for months or even
      years. Dental professionals must be sufficiently familiar with the clinical
      manifestations of pemphigus vulgaris to ensure early diagnosis and treatment,
      since this in turn determines the prognosis and course of the disease. This
      article presents a case report with unknown etiology along with an overview of
      the disease.

PMID- 21957394
TI  - Prosthodontic rehabilitation of dentinogenesis imperfecta.
AB  - Dentinogenesis imperfecta and its prosthodontic management is a challenging task.
      Treatment protocol varies according to clinical case. Although various reports in
      the literature suggest general guidelines for treatment planning, the present
      case report describes a full mouth rehabilitation of a young patient with
      dentinogenesis imperfecta treated by maxillary fixed partial dentures and
      mandibular fiber reinforced overdenture with metal occlusal surfaces.

PMID- 21957395
TI  - Modified bracket positioning holder.

PMID- 21957396
TI  - Stabilization of Gas Bubbles Released from Water-Soluble Carbohydrates Using
      Amphiphilic Compounds: Preparation of Formulations and Acoustic Monitoring of
      Bubble Lifetime.
AB  - The ultrasound contrast agents Echovist((r)) and Levovist((r)) (Bayer AG,
      Schering AG, Germany) are based on the release of gas bubbles from milled alpha-d
      galactose. In diagnostic ultrasound, for this class of contrast agents, there is
      a need for prolonged contrast duration. To investigate if new carbohydrate
      compositions could prolong the lifetime of the gas bubbles, alpha-d-galactose was
      mixed with other carbohydrates or amphiphiles with varying log P. Acoustic
      attenuation vs. time (390 s) area under the curve (A(390)) and bubble half-time
      (t1/2) were used as measures of prolonged lifetime of gas bubbles. The products,
      to which 0.1% of a lipophilic carboxylic acid (5beta-cholanic acid, behenic acid,
      and melissic acid) has been added, showed more than 5, 7 and 11 times enhancement
      of A(390), respectively, compared with the reference compound 2 (RC2)
      corresponding to the commercial product Levovist(r). The half-time t 1/2 of the
      same compounds was prolonged more than 6 times compared with RC2. A partial least
      square (PLS) statistical analysis confirmed that, for additives, high log P
      carboxylic acids lead to the highest A(390). The present results bear a promise
      of products with a more persistent in vivo ultrasound contrast effect than the
      commercially available agents.

PMID- 21957397
TI  - Advance directives and the family: French and American perspectives.
AB  - Several studies have explored differences between North American and European
      doctor-patient relationships. They have focused primarily on differences in
      philosophical traditions and historic and socio-economic factors between these
      two regions that might lead to differences in behaviour, as well as divergent
      concepts in and justifications of medical practice. However, few empirical
      intercultural studies have been carried out to identify in practice these
      cultural differences. This lack of standard comparative empirical studies led us
      to compare differences between France and the USA regarding end-of-life decision
      making. We tested certain assertions put forward by bioethicists concerning the
      impact of culture on the acceptance of advance directives in such decisions. In
      particular, we compared North American and French intensive care professional's
      attitudes toward: 1) advance directives and 2) the role of the family in
      decisions to withhold or withdraw life-support.

PMID- 21957398
TI  - Tracing personalized health curves during infections.
AB  - It is difficult to describe host-microbe interactions in a manner that deals well
      with both pathogens and mutualists. Perhaps a way can be found using an
      ecological definition of tolerance, where tolerance is defined as the dose
      response curve of health versus parasite load. To plot tolerance, individual
      infections are summarized by reporting the maximum parasite load and the minimum
      health for a population of infected individuals and the slope of the resulting
      curve defines the tolerance of the population. We can borrow this method of
      plotting health versus microbe load in a population and make it apply to
      individuals; instead of plotting just one point that summarizes an infection in
      an individual, we can plot the values at many time points over the course of an
      infection for one individual. This produces curves that trace the course of an
      infection through phase space rather than over a more typical timeline. These
      curves highlight relationships like recovery and point out bifurcations that are
      difficult to visualize with standard plotting techniques. Only nine archetypical
      curves are needed to describe most pathogenic and mutualistic host-microbe
      interactions. The technique holds promise as both a qualitative and quantitative
      approach to dissect host-microbe interactions of all kinds.

PMID- 21957399
TI  - Management of the patient with a central airway obstruction.

PMID- 21957400
TI  - Anesthesiologists work-related exhaustion: A comparison study with other hospital
      employees.
AB  - BACKGROUND: Anesthesia is a demanding occupation due to long working hours,
      sustained vigilance, unpredictability of stressful situation, fear of litigation,
      competence, and production pressure. Work-related exhaustion can lead to several
      physical and psychological symptoms and delay decision making. The aim of this
      study was to evaluate how different work conditions affect personnel exhaustion
      by studying a sample of anesthesiologists comparing them with ophthalmologists
      and ancillary hospital staff METHODS: One hundred fifty persons divided into
      three equal groups (50 each) were invited to participate in this study. Subjects
      were asked to answer two self report questionnaires: The Multidimensional Fatigue
      Inventory (MFI-20) and General Health Questionnaire (GHQ-12) which used to assess
      work related exhaustion and mental health, respectively. RESULTS:
      Multidimensional Fatigue Inventory scale (MFI 20) and General Health
      Questionnaire (GHQ 12) were significantly higher in anesthesiologists than in
      other groups (P = 0.001). Different aspects of work-related exhaustion showed
      that general, physical and mental fatigue were significantly higher in
      anesthesiologists (P = 0.002 and 0.001, respectively). Reduced activity and
      reduced motivation were also higher in anesthesiologists compare to the other
      groups (P = 0.005 and 0.001, respectively). CONCLUSION: Work-related exhaustion
      under the current study is more obvious among anesthesiologists. Ophthalmologist
      and ancillary hospital employees felt that they had less stress at their work.

PMID- 21957401
TI  - The evaluation of upper leg traction in lateral position for pediatric caudal
      block.
AB  - PURPOSE: A well-functioning caudal block is an excellent adjunct to general
      anesthesia, but misplaced injection results in poor analgesia as well as
      possibility of serious morbidity. Therefore, the purpose of this study was to
      evaluate the effectiveness of leg traction on success rate of caudal block in
      lateral position in children. METHODS: Two hundred children, age 2 months to 6
      years, ASA I and II, who underwent lower abdominal surgeries were randomized in
      prospective controlled clinical trial study in two groups. After induction of
      General anesthesia, the caudal block was performed in the lateral position with
      upper leg traction (L-T-) or with the standard position (S-P) (leg flexed 90
      degrees ). Hemodynamicchanges, movement of lower extremity in response to
      surgical stimulus were evaluated. RESULTS: There was no significant difference in
      caudal block's success rate between two groups at first attempt (P=0.25). In
      group (S-P) the procedure was successful in 60% of cases at first attempt, 25% at
      second,10% at third attempt and 5% failure of caudal block, whereas in the first
      group it was 75%, 20%, 1% and 4% of cases respectively. There were no significant
      differences in heart rate and blood pressure changes between two groups (P>0.05).
      CONCLUSION: The success rate of pediatric caudal block in upper leg traction did
      not differ from that of the standard position.

PMID- 21957402
TI  - A randomized controlled trial to compare pregabalin with gabapentin for
      postoperative pain in abdominal hysterectomy.
AB  - BACKGROUND: Pregabalin is a potent ligand for alpha-2-delta subunit of voltage
      gated calcium channels in the central nervous system, which exhibits potent
      anticonvulsant, analgesic and anxiolytic activity. The pharmacological activity
      of pregabalin is similar to that of gabapentin and shows possible advantages.
      Although it shows analgesic efficacy against neuropathic pain, very limited
      evidence supports its postoperative analgesic efficacy. We investigated its
      analgesic efficacy in patients experiencing acute pain after abdominal
      hysterectomy and compared it with gabapentin and placebo. METHODS: A randomized,
      double-blind, placebo-controlled study was conducted in 90 women undergoing
      abdominal hysterectomy who were anaesthetized in a standardized fashion. Patients
      received 300 mg pregabalin, 900 mg gabapentin or placebo, 1-2 hours prior to
      surgery. Postoperative analgesia was administered at visual analogue scale (VAS)
      >=3. The primary outcome was analgesic consumption over 24 hours and patients
      were followed for pain scores, time to rescue analgesia and side effects as
      secondary outcomes. RESULTS: The diclofenac consumption was statistically
      significant between pregabalin and control groups, and gabapentin and control
      groups; however, pregabalin and gabapentin groups were comparable. Moreover, the
      consumption of tramadol was statistically significant among all the groups.
      Patients in pregabalin and gabapentin groups had lower pain scores in the initial
      hour of recovery. However, pain scores were subsequently similar in all the
      groups. Time to first request for analgesia was longer in pregabalin group
      followed by gabapentin and control groups. CONCLUSION: A single dose of 300 mg
      pregabalin given 1-2 hours prior to surgery is superior to 900 mg gabapentin and
      placebo after abdominal hysterectomy. Both the drugs are better than placebo.

PMID- 21957403
TI  - A comparison of the ratio of patient's height to thyromental distance with the
      modified Mallampati and the upper lip bite test in predicting difficult
      laryngoscopy.
AB  - BACKGROUND: THE AIM OF THE PRESENT STUDY WAS TO COMPARE THE ABILITY TO PREDICT
      DIFFICULT VISUALIZATION OF THE LARYNX FROM THE FOLLOWING PREOPERATIVE AIRWAY
      PREDICTIVE INDICES, IN ISOLATION AND COMBINATION: modified Mallampati test (MMT),
      the ratio of height to thyromental distance (RHTMD) and the Upper-Lip-Bite test
      (ULBT). METHODS: We collected data on 603 consecutive patients scheduled for
      elective surgery under general anesthesia requiring endotracheal intubation and
      then evaluated all three factors before surgery. An experienced anesthesiologist,
      not informed of the recorded preoperative airway evaluation, performed the
      laryngoscopy and grading (as per Cormack and Lehane's classification).
      Sensitivity, specificity, and positive and negative predictive value, Receiver
      operating characteristic (ROC) Curve and the area under ROC curve (AUC) for each
      airway predictor in isolation and in combination were determined. RESULTS:
      Difficult laryngoscopy (Grade 3 or 4) occurred in 41 (6.8%) patients. The main
      endpoint of the present study, the AUC of the ROC, was significantly lower for
      the MMT (AUC, 0.511; 95% CI, 0.470-0.552) than the ULBT (AUC, 0.709; 95% CI,
      0.671-0.745, P=0.002) and the RHTMD score (AUC, 0.711; 95% CI, 0.673-0.747,
      P=0.001). There was no significant difference between the AUC of the ROC for the
      ULBT and the RHTMD score. By using discrimination analysis, the optimal cutoff
      point for the RHTMD for predicting difficult laryngoscopy was 21.06 (sensitivity,
      75.6%; specificity, 58.5%). CONCLUSION: The RHTMD is comparable with ULBT for
      prediction of difficult laryngoscopy in general population.

PMID- 21957404
TI  - Use of transesophageal Doppler as a sole cardiac output monitor for reperfusion
      hemodynamic changes during living donor liver transplantation: An observational
      study.
AB  - AIMS: To report the use of transesophageal Doppler (TED), a minimally invasive
      cardiac output (COP) monitor, before, during and after reperfusion and study its
      effect on anesthetic management during living donor liver transplantation (LDLT).
      SETTING AND DESIGN: A prospective observational study. METHODS: A total of 25
      consecutive recipients with a MELD score between 15 and 20 were enrolled. Data
      were recorded at baseline (TB); anhepatic phase (TA); and post-reperfusion - 1,
      5, 10 and 30 minutes. Fluid therapy was guided by corrected flow time (FTc) of
      the TED. Packed red blood cells (RBCs) were only given when hematocrit was less
      than 25%. Rotational thromboelastometry (ROTEM) and standard laboratory tests
      were used to guide component blood products requirements. RESULTS: Post
      reperfusion, the COP, Cardiac Index (CI) and stroke volume (SV) increased
      significantly at all points of measurements; this was associated with a
      significant decrease in systemic vascular resistance (SVR) (P ;< .05).
      Immediately post-reperfusion, for 5 minutes, mean arterial blood pressure (ABP)
      dropped significantly (P < .05), and 14 out of the 25 patients required boluses
      of epinephrine (10 MUg) to restore the mean ABP; 3 of the 14 patients required
      norepinephrine infusion till the end of surgery. Central venous pressure (CVP)
      and urine output (UOP) at all measures were maintained adequately with FTc-guided
      fluid replacement. Eight out of the 25 patients required no blood transfusion,
      and 4 of the 8 patients required no catecholamine support. CONCLUSION: TED as a
      sole monitor for COP was able to present significant and reliable changes in the
      cardiovascular status of the recipients during reperfusion, which could help to
      guide fluid- and drug-supportive therapy in this population of patients. This
      preliminary study needs to be applied on a larger scale.

PMID- 21957405
TI  - Comparison of streamlined liner of the pharynx airway (SLIPATM) with the
      laryngeal mask airway ProsealTM for lower abdominal laparoscopic surgeries in
      paralyzed, anesthetized patients.
AB  - CONTEXT: Supraglottic airway devices have been used as an alternative to tracheal
      intubation during laparoscopic surgery. AIMS: The study was designed to compare
      the efficacy of Streamlined Liner of the Pharynx Airway (SLIPA) for positive
      pressure ventilation and postoperative complications with the Laryngeal Mask
      Airway ProSeal (PLMA) for patients undergoing lower abdominal laparoscopies under
      general anesthesia with controlled ventilation. SETTINGS AND DESIGN: Prospective,
      crossover randomized controlled trial performed on patients undergoing lower
      abdominal laparoscopic surgeries. METHODS: A total of 120 patients undergoing
      lower abdominal laparoscopic surgeries were randomly allocated into two equal
      groups; PLMA and SLIPA groups. Number of intubation attempts, insertion time,
      ease of insertion, and fiberoptic bronchoscopic view were recorded. Lung
      mechanics data were collected 5 minutes after securing the airway, then after
      abdominal insufflation. Blood traces and regurgitation were checked for;
      postoperative sore throat and other complications were recorded. STATISTICAL
      ANALYSIS: Arithmetic mean and standard deviation values were calculated and
      statistical analyses were performed for each group. Independent sample t-test was
      used to compare continuous variables exhibiting normal distribution, and Chi
      squared test for noncontinuous variables. P value <0.05 was considered
      significant. RESULTS: Insertion time, first insertion success rate, and ease of
      insertion were comparable in both groups. Fiberoptic bronchoscopic view was
      significantly better and epiglottic downfolding was significantly lower in SLIPA
      group. Sealing pressure and lung mechanics were similar. Gastric distension was
      not observed in both groups. Postoperative sore throat was significantly higher
      in PACU in PLMA group. Blood traces on the device were significantly more in
      SLIPA group. CONCLUSIONS: SLIPA can be used as a useful alternative to PLMA in
      patients undergoing lower abdominal laparoscopic surgery with muscle relaxant and
      controlled ventilation.

PMID- 21957406
TI  - Epidural anesthesia and post-operative analgesia for bilateral inguinal mesh
      hernioplasty: Comparison of equipotent doses of ropivacaine and bupivacaine.
AB  - OBJECTIVES: Ropivacaine is a long-acting amide local anesthetic, which is
      structurally very similar to bupivacaine but produces less motor block and less
      cardiac and central nervous system toxicity. It is also about 40% less potent
      than bupivacaine. Our double blind study was designed to compare the clinical
      efficacy of the equipotent doses of ropivacaine 0.75% and bupivacaine 0.5% for
      epidural anesthesia and ropivacaine 0.2% and bupivacaine 0.125% for post
      operative analgesia in patients undergoing bilateral mesh hernioplasty. METHODS:
      Sixty-one patients were randomized to receive 15 ml of 0.75% ropivacaine or 0.5%
      bupivacaine. Sensory and motor block characteristics were compared. Changes in
      heart rate, mean arterial blood pressure, and adverse effects were noted. For
      post-operative analgesia, 0.2% ropivacaine and 0.125% bupivacaine were given as
      continuous epidural infusion. Analgesia using VAS scores, motor block, volume of
      local anesthetic used and patient satisfaction was assessed. RESULTS: There was
      no significant variation in the sensory block profile. A greater intensity of
      motor block was achieved with bupivacaine in the beginning but by 30 minutes the
      difference was not significant. Duration of motor block was similar in the two
      groups. Visual analog scale scores were similar in both groups during the post
      operative period, with a similar motor block profile. No major side effects were
      noted in any group. CONCLUSION: The equipotent doses of ropivacaine and
      bupivacaine provided good quality epidural anesthesia and post-operative
      analgesia.

PMID- 21957407
TI  - A single-centre randomized-controlled trial to study effect of dilution on
      propofol-induced injection pain at injection site.
AB  - BACKGROUND: Propofol is a commonly used short-acting intravenous anaesthetic
      agent. A major disadvantage of propofol is pain at injection site with high
      incidence up to 90%. Various modalities have been tried to obtund propofol
      induced pain; however, search for an ideal agent continues. We assessed the
      effect of double and triple dilution of 1% propofol emulsion with normal saline
      on pain at injection site. METHODS: This randomized, double-blinded study was
      done on 60 adult patients of both sexes, belonging to ASA grade I and II
      scheduled for elective surgery under general anesthesia, divided into three
      groups named I, II, III of 20 patients each. The patients of group I, II, and III
      received 1% propofol 2 ml, 0.5% propofol 4 ml, and 0.33% propofol 6 ml,
      respectively, over a period of 4 s and pain felt was assessed. RESULTS: There was
      no statistically significant difference in the pain score in group II as compared
      to patients in group I. However, there was a statistically significant decrease
      in the pain score in group III as compared to patients in group I (P value 0.02)
      and group II (P value 0.03). CONCLUSIONS: We found a significant decrease in both
      incidence and severity of pain during injection with a 0.33% propofol solution
      without significant adverse hemodynamic effects. The small size of data was a
      limitation in our study and a large-scale study will be needed to prove its
      therapeutic beneficence.

PMID- 21957408
TI  - Start time delays in operating room: Different perspectives.
AB  - BACKGROUND: Healthcare expenditure is a serious concern, with escalating costs
      failing to meet the expectations of quality care. The treatment capacities are
      limited in a hospital setting and the operating rooms (ORs). Their optimal
      utilization is vital in efficient hospital management. Starting late means
      considerable wait time for staff, patients and waste of resources. We planned an
      audit to assess different perspectives of the residents in surgical specialities
      and anesthesia and OR staff nurses so as to know the causative factors of
      operative delay. This can help develop a practical model to decrease start time
      delays in operating room (ORs). AIMS: An audit to assess different perspectives
      of the Operating room (OR) staff with respect to the varied causative factors of
      operative delay in the OR. To aid in the development of a practical model to
      decrease start time delays in ORs and facilitate on-time starts at Jai Prakash
      Narayan Apex Trauma centre (JPNATC), All India Institute of Medical Sciences
      (AIIMS), New Delhi. METHODS: We prepared a questionnaire seeking the five main
      reasons of delay as per their perspective. RESULTS: The available data was
      analysed. Analysis of the data demonstrated the common causative factors in start
      time operative delays as: a lack of proper planning, deficiencies in team work,
      communication gap and limited availability of trained supporting staff.
      CONCLUSIONS: The preparation of the equipment and required material for the OR
      cases must be done well in advance. Utilization of newer technology enables
      timely booking and scheduling of cases. Improved inter-departmental coordination
      and compliance with preanesthetic instructions needs to be ensured. It is
      essential that the anesthesiologists perform their work promptly, well in time .
      and supervise the proceedings as the OR manager. This audit is a step forward in
      defining the need of effective OR planning for continuous quality improvement.

PMID- 21957409
TI  - Intra and postoperative outcome of adding clonidine to bupivacaine in
      infraorbital nerve block for young children undergoing cleft lip surgery.
AB  - AIMS AND CONTEXT: To evaluate the efficacy of adding clonidine to bupivacaine in
      bilateral infraorbital nerve block for hemodynamic changes, requirement of
      opioids, volatile agent, and muscle relaxants intraoperatively and relief of pain
      postoperatively SETTING AND DESIGN: Prospective, randomized, double-blind study.
      METHODS: Fifty pediatric patients aged less than 24 months undergoing elective
      cleft lip repair were randomly allocated to two groups of 25 each. After tracheal
      intubation, group A received bilateral infraorbital nerve block with 1 ml
      solution of clonidine (1 MUg/kg) and bupivacaine 0.25%, and group B received 1 ml
      of 0.25% bupivacaine. Hemodynamic parameters, intraoperative requirement of
      volatile anesthetic agent, muscle relaxant, and analgesic were recorded. Pain was
      assessed postoperatively using the Face, Legs, Activity, Cry, Consolability scale
      till the first rescue drug was given. STATISTICAL ANALYSIS: Two sample unpaired t
      test and the correlation r test. RESULTS: The duration of analgesia from the time
      of administration of block in group A was 667.72 +/- 210.74 min compared to
      558.48 +/- 150.28 min in group B (P<0.05). CONCLUSION: Addition of clonidine as
      an adjunct to local anesthetic significantly decreased the requirement of other
      anesthetic drugs and significantly prolonged the duration of postoperative
      analgesia without any adverse effects.

PMID- 21957410
TI  - A comparison of the sedative, hemodynamic, and respiratory effects of
      dexmedetomidine and propofol in children undergoing magnetic resonance imaging.
AB  - AIM: To compare the sedative, hemodynamic, and respiratory effects of
      dexmedetomidine and propofol in children undergoing magnetic resonance imaging
      procedures. METHODS: Sixty children between the age of 1 to 7 years were randomly
      distributed into two groups: The dexmedetomidine (D) group received 1 MUg/kg
      initial dose followed by continuous infusion of 0.5 MUg/kg/h, and the propofol
      group (P) received 3 mg/kg initial dose, followed by a continuous infusion of 100
      MUg/kg/min. Inadequate sedation was defined as difficulty in completing the
      procedure because of the child's movement during magnetic resonance imaging. Mean
      arterial pressure (MAP), heart rate, peripheral oxygen saturation, and
      respiratory rate (RR) were recorded during the study. RESULT: The onset of
      sedation, recovery, and discharge time were significantly shorter in group P than
      in group D. MAP, heart rate, and RR decreased during sedation from the baseline
      values in both groups. MAP and RR were significantly lower in group P than in
      group D during sedation. Dexmedetomidine and propofol provided adequate sedation
      in most of the children. CONCLUSION: We conclude that although propofol provided
      faster anesthetic induction and recovery times, it caused hypotension and
      desaturation. Dexmedetomidine could be an alternative, reliable sedative drug to
      propofol in selected patients.

PMID- 21957411
TI  - Percutaneous tracheotomy: Forceps vs. cone dilatation techniques.
AB  - BACKGROUND: Percutanoeous tracheotomy (PT) is a minimal invasive procedure
      alternative to surgical tracheotomy. PT offers an added advantage of enormous
      decrease of time interval between decision of doing tracheotomy and actually
      doing it. Moreover hazards of patient transport can be avoided as it can be
      safely performed at the bedside. We started doing PT in 2003 and performed 100
      cases using forceps dilatation. Later we switched over to cone dilatation where
      we performed 215 cases. This study aims to compare two techniques of forceps vs.
      cone dilatation methods for PT. METHODS: A total of 100 cases of PT were
      performed starting from December 2003 to August 2005 using the forceps dilatation
      method (group A). Further 215 cases were conducted (group B) from September 2003
      to July 2008 using the cone dilatation method. Time of performing both procedures
      was recorded. Also incidence of complications was also recorded in both groups.
      RESULTS: The incidence of minor bleeding in group A was 9%, whereas in group B
      was 5.58%. Major bleeding occurred in two patients in group B. Both cases
      suffered of pneumothorax and emphysema. One patient developed life-threatening
      tension pneumothorax and required cardio pulmonary resuscitation. This was one
      case in this series, in which the procedure has contributed to patient's
      morbidity. Guide wire-related technical difficulties were seen in 2% of the cases
      in group A, and 3.7% of cases in group B. CONCLUSION: forceps dilatation PT is
      superior to the cone dilatation technique in terms of safety. Further studies are
      needed to confirm our results.

PMID- 21957412
TI  - Authors, editors, and the signs, symptoms and causes of plagiarism.
AB  - Plagiarism and inadequate citing appear to have reached epidemic proportions in
      research publication. This article discusses how plagiarism is defined and
      suggests some possible causes for the increase in the plagiarism disease. Most
      editors do not have much tolerance for text re-use with inadequate citation
      regardless of reasons why words are copied from other sources without correct
      attribution. However, there is now some awareness that re-use of words in
      research articles to improve the writing or "the English" (which has become a
      common practice) should be distinguished from intentional deceit for the purpose
      of stealing other authors' ideas (which appears to remain a very rare practice).
      Although it has become almost as easy for editors to detect duplicate text as it
      is for authors to re-use text from other sources, editors often fail to consider
      the reasons why researchers resort to this strategy, and tend to consider any
      text duplication as a symptom of serious misconduct. As a result, some authors
      may be stigmatized unfairly by being labeled as plagiarists. The article
      concludes with practical advice for researchers on how to improve their writing
      and citing skills and thus avoid accusations of plagiarism.

PMID- 21957413
TI  - Negative pressure pulmonary edema revisited: Pathophysiology and review of
      management.
AB  - Negative pressure pulmonary edema (NPPE) is a dangerous and potentially fatal
      condition with a multifactorial pathogenesis. Frequently, NPPE is a manifestation
      of upper airway obstruction, the large negative intrathoracic pressure generated
      by forced inspiration against an obstructed airway is thought to be the principal
      mechanism involved. This negative pressure leads to an increase in pulmonary
      vascular volume and pulmonary capillary transmural pressure, creating a risk of
      disruption of the alveolar-capillary membrane. The early detection of the signs
      of this syndrome is vital to the treatment and to patient outcome. The purpose of
      this review is to highlight the available literature on NPPE, while probing the
      pathophysiological mechanisms relevant in both the development of this condition
      and that involved in its resolution.

PMID- 21957414
TI  - Fully successful resuscitation despite prolonged cardiac arrest.
AB  - Sudden cardiac arrest following spinal anesthesia is a relatively common and
      often fatal complication. Careful patient selection, appropriate dosing of the
      local anesthetic, volume loading, close monitoring and prompt intervention at the
      first sign of cardiovascular instability should improve outcomes.

PMID- 21957415
TI  - Anesthesia implications in emergency oncologic surgery in a case of untreated
      Parkinsonism.
AB  - Oncologic surgery has made tremendous advancements in the last two decades. The
      prognosis of once thought to be irreversible and incurable diseases has improved
      dramatically with these advancements, which have given a fresh lease of hope to
      the general population. But there are certain factors that are still unfavorable
      for achieving improved outcome of surgery in various cancers. The associated
      comorbid diseases do determine to a large extent the actual outcome of all the
      interventions to treat oncologic disease. The untreated coexisting disease makes
      the task of the attending anesthesiologist very challenging as numerous
      complications are anticipated, especially during emergency surgery. We are
      describing a case of a patient with endometrial carcinoma who presented with
      unstoppable bleeding per-vaginum and was suffering from Parkinson disease since
      11/2 years, for which no treatment was ever sought. Vaginal hysterectomy was
      performed under graded epidural anesthesia; and after a smooth and uneventful
      postoperative period of 8 days, she was referred to radiotherapy unit for further
      management.

PMID- 21957416
TI  - Low-dose sequential combined-spinal epidural anesthesia for Cesarean section in
      patient with uncorrected tetrology of Fallot.
AB  - Tetrology of Fallot (TOF) is the most commonly encountered congenital cardiac
      lesion in pregnancy. Although there are controversies regarding safe anesthetic
      technique for parturient with TOF, we use low-dose sequential combined-spinal
      epidural anesthesia in such a case posted for Cesarean section and found that low
      dose (0.5 ml of 0.5%) intrathecal bupivacaine and fentanyl with sequential
      epidural bupivacaine supplementation was adequate for the performance of an
      uncomplicated Cesarean section with minimal side effects and good fetal outcome.
      Thus, though the choice of anesthesia can vary in such patients, low-dose
      sequential combined-spinal epidural can be a safe alternate to achieve good
      anesthesia with impressive cardiovascular stability.

PMID- 21957417
TI  - Neurogenic pulmonary edema after rupture of intracranial aneurysm during
      endovascular coiling.
AB  - Neurogenic pulmonary edema (NPE) is a well-known entity, occurs after acute
      severe insult to the central nervous system. It has been described in relation to
      different clinical scenario. However, NPE has rarely been mentioned after
      endovascular coiling of intracranial aneurysms. Here, we report the clinical
      course of a patient who developed NPE after aneurysmal rupture during
      endovascular surgery. There was significant cardiovascular instability possibly
      from stimulation of hypothalamus adjacent to the site of aneurysm. This case
      highlights the predisposition of minimally invasive procedures like endovascular
      coiling to life-threatening complications such as NPE.

PMID- 21957418
TI  - Anesthetic considerations of central airway obstruction.
AB  - Central airway obstruction (CAO) is a serious presentation of lung cancer and
      associated chest diseases. It presents a real challenge to the anesthesiologist
      because usually the patient admitted to the hospital as an emergency case with
      high grade dyspnea scheduled to undergo rigid bronchoscopy for diagnostic and
      possible therapeutic interventions. In this case report, we described the
      anesthetic management of a patient who was admitted to our hospital with CAO.

PMID- 21957419
TI  - Tracheal intubation in the prone position with an intubating laryngeal mask
      airway following posterior spine impaled knife injury.
AB  - A prone position is not a standard position for anesthesia induction and
      associated with problems like difficult mask fit, impairment of orotracheal
      intubation by direct laryngoscopy, and reduction of pulmonary compliance. However
      anesthetic management of trauma victims presenting with penetrating posterior
      lumbar spine injury requires airway securement and induction of anesthesia in the
      prone position to avoid further neurological impairment. We herein present the
      first reported case of an adult trauma patient presented with an impaled knife
      protruding out of lower back, who underwent endotracheal intubation with an
      intubating laryngeal mask airway under general anesthesia in the prone position.
      Our experience indicates that this technique would be easier and less risky
      compared to direct laryngoscopy or awake fiber optic intubation and might be
      considered in an emergency situation.

PMID- 21957420
TI  - Postoperative hypoxemia due to fat embolism.
AB  - Although the reported incidence of fat embolism syndrome (FES) is low
      (approximately 1%), it is likely that microscopic fat emboli are showered during
      manipulation of long bone fractures. Even though there continues to be debate
      regarding the etiology and proposed mechanism responsible for FES, significant
      systemic manifestations may occur. Treatment is generally symptomatic based on
      the clinical presentations. We report a 10-year-old girl who developed hypoxemia
      following treatment of a displaced Salter-Harris type II fracture of the distal
      tibia. The subsequent evaluation and hospital course pointed to fat embolism as
      the most likely etiology for the hypoxemia. We discuss the etiology for FES,
      review the proposed pathophysiological mechanisms responsible for its clinical
      manifestations, present currently accepted diagnostic criteria, and discuss its
      treatment.

PMID- 21957421
TI  - Ogilvie's syndrome following cesarean delivery: The Dubai's case.
AB  - We present a case of acute colonic pseudo obstruction (Ogilvie's Syndrome) post
      Cesarean Section in a 35 years old Arabic patient with co-existing systemic lupus
      erythematosus. Due to developed complications-perforations of the colon and
      peritonitis, the patient required laparotomy and right hemicolectomy. To our
      knowledge, this is the first case of Ogilvie's syndrome, reported from the Middle
      East. The possible etiologic factors, pathophysiology, clinical presentation,
      diagnostic work up and treatment are discussed. The need for awareness about the
      syndrome and early diagnosis is emphasized.

PMID- 21957422
TI  - Role of clonidine in perioperative acute atrial fibrillation.
AB  - We report a case of acute onset atrial fibrillation (AF) that presented for
      emergency surgery where rate control and sinus rhythm were successfully achieved
      using clonidine. Patient had acute AF with high blood pressure. Metoprolol failed
      to decrease the ventricular rate and blood pressure but with clonidine, we could
      achieve both the goals. Also, rhythm reverted to a sinus rhythm and continued to
      be in sinus rhythm after administering clonidine.

PMID- 21957423
TI  - Potential role of coronary computed tomography angiogram in cardiac preoperative
      evaluation.
AB  - Preoperative assessment of the cardiac patients before noncardiac surgery is
      concern in the clinical practice of anesthesiologist, surgeon, and medical
      consultant. The preferred stress testing is exercise electrocardiogram (ECG) in
      patients who are able to exercise and have normal ECG; however, either stress
      myocardial perfusion scintigraphy (MPS) or stress echocardiography is necessary
      if further testing is appropriately indicated before surgery. Unfortunately,
      stress MPs or stress echocardiography is not widely available and has some
      limitations. Coronary computed tomography angiogram (CCTA) has demonstrated
      excellent diagnostic accuracy in detecting coronary artery disease and accurate
      left ventricle function measurement. CCTA seems to be feasible, reliable, and has
      strong potential of becoming sole screening test before surgery.

PMID- 21957424
TI  - Anesthetic considerations and difficult airway management in a case of Noonan
      syndrome.
AB  - Noonan syndrome is a genetically transmitted autosomal dominant disorder
      characterized by various anatomic anomalies and pathophysiologic derangements.
      Anesthetic management in such cases poses a multitude of challenges, especially
      related to the airway management and maintenance of cardiovascular stability. We
      report a case of a 9-year-old male child weighing 24 kg, who was diagnosed as a
      case of Noonan syndrome and had undergone ligation of patent ductus arteriosus
      during early childhood. The child was operated on for release of bilateral neck
      bands under general anesthesia. The case report pertains to the successful airway
      and anesthetic management in the background of difficult airway and existence of
      various cardiac lesions.

PMID- 21957425
TI  - Cerebral Fat Embolism: A diagnostic challenge.
AB  - Fat embolism syndrome (FES) is a rare but a serious clinical catastrophe
      occurring after traumatic injury to long bones. Cerebral involvement in the
      absence of pulmonary or dermatological manifestation on initial presentation may
      delay the diagnosis of cerebral fat embolism (CFE). We discuss a case series of
      CFE which posed a challenge in diagnosis. The clinical presentations of these
      patients did not satisfy the commonly used clinical criteria for aiding the
      diagnosis of FES. Early MRI brain (DWI and T2 weighted sequences) in patients
      with neurological symptoms after trauma even in the absence of pulmonary and
      dermatological findings should be the goal.

PMID- 21957426
TI  - Common carotid artery surprise during percutaneous dilatational tracheostomy - A
      near miss, confirmed with ultrasound.
AB  - The practice of percutaneous dilatational tracheostomy (PDT) has gained
      popularity and acceptance due to the ease in acquiring its skill and low
      probability of complications. Nevertheless, PDT is associated with a few
      complications, some really life-threatening. We present a case of an abnormally
      located common carotid artery encountered during PDT in our intensive care unit.
      The procedure was electively posted, in an old patient chronically ventilated
      after a revived cardiac arrest. While identifying the landmarks on palpation
      pulsation was felt similar to arterial pulsation. This was confirmed using
      bedside portable ultrasonography and found to be the right common carotid artery
      forming a loop anterior to the trachea at the level of the third and fourth
      tracheal rings. The patient had a past history of thyroidectomy and this was
      suspected to be the primary reason for the altered course of the right common
      carotid artery.

PMID- 21957427
TI  - Oral oxygenating airway.

PMID- 21957428
TI  - Advancing breast cancer therapy by translational research: highlights of the
      Improving Care and Knowledge through Translational Research (IMPAKT) breast
      cancer conference.

PMID- 21957429
TI  - Extending the duration of first-line chemotherapy in metastatic breast cancer: a
      perspective review.
AB  - The treatment of metastatic breast cancer is mainly palliative, but optimal
      management might result in survival improvement as well. For this reason, many
      trials have attempted to optimize the therapeutic approach in this disease
      setting. Among the possible options, chemotherapy represents the backbone of the
      treatment and survival improvements that have been shown by the use of modern
      chemotherapeutic agents. Whereas the type of chemotherapy is generally dictated
      by patient characteristics and those of their disease, substantial controversy
      still remains on how long chemotherapy should be administered after disease
      control is achieved. In this review, we have analysed all available evidence on
      the duration of first-line chemotherapy in advanced breast cancer.

PMID- 21957431
TI  - Therapeutic options in cutaneous melanoma: latest developments.
AB  - Melanoma is a malignancy that is highly curable in the early stages but has
      devastating consequences in later stages due to lack of response to traditional
      treatments. Improved understanding of the basic science of tumorigenesis has
      helped lead to novel targeted therapies which are producing beneficial results in
      patients with melanoma. Enhancement of the immune system by blockade of the
      cytotoxic T-lymphocyte associated antigen-4 by the monoclonal antibody ipilimumab
      is now approved by the United States Food and Drug Administration (FDA) for use
      in patients with unresectable melanoma. The approval of this drug was based on
      the first ever data in melanoma showing an improvement in overall survival. New
      advances in targeting components of the mitogen-activated protein kinase pathway
      are showing impressive responses in clinical trials in most patients harboring
      activating mutations in BRAF. Thus, this is a new era in the management of
      melanoma and we review the recent progress made in treating patients with
      advanced disease.

PMID- 21957430
TI  - Denosumab for the treatment of bone metastases in breast cancer: evidence and
      opinion.
AB  - INTRODUCTION: Denosumab, a fully human monoclonal antibody, targets the receptor
      activator of nuclear factor-kappaB (RANK) ligand, a protein essential for
      osteoclast differentiation, activity and survival. Loss of osteoclasts from the
      bone surface reduces bone turnover and bone loss in malignant and benign
      diseases. In breast cancer, bone metastases are frequently observed; cancer
      treatment-induced bone loss (CTIBL) may result as a consequence of endocrine
      treatment or chemotherapy. Furthermore, preclinical studies suggest a direct role
      of the RANK/RANK-ligand pathway in breast tumorigenesis. This paper reviews
      preclinical and clinical data on denosumab in breast cancer. MATERIALS AND
      METHODS: Studies were identified through the Medline database. Key search terms
      included: AMG-162, bisphosphonates, denosumab, RANK-ligand and zoledronic acid.
      Information available in abstract form only was retrieved from major oncology
      meetings, such as the American Society of Clinical Oncology (ASCO) annual
      meeting, ASCO breast meeting, European Cancer Organization, European Society of
      Medical Oncology and the San Antonio Breast Cancer Symposium. RESULTS: Denosumab
      was consistently well tolerated throughout clinical trials, although the observed
      incidence of osteonecrosis of the jaw was comparable to that with
      bisphosphonates. Efficacy as determined by a reduction of skeletal-related events
      was at least equal to zoledronic acid, and superior in one phase III study
      conducted in patients with metastatic breast cancer. Clinical trials
      investigating the role of denosumab for the prevention of CTIBL and breast cancer
      recurrences are currently ongoing. CONCLUSION: In conclusion, denosumab appears
      to be an effective and safe treatment option in patients with bone metastases
      from breast cancer with the potential of also preventing CTIBL.

PMID- 21957432
TI  - Evolving scalable and modular adaptive networks with Developmental Symbolic
      Encoding.
AB  - Evolutionary neural networks, or neuroevolution, appear to be a promising way to
      build versatile adaptive systems, combining evolution and learning. One of the
      most challenging problems of neuroevolution is finding a scalable and robust
      genetic representation, which would allow to effectively grow increasingly
      complex networks for increasingly complex tasks. In this paper we propose a novel
      developmental encoding for networks, featuring scalability, modularity,
      regularity and hierarchy. The encoding allows to represent structural
      regularities of networks and build them from encapsulated and possibly reused
      subnetworks. These capabilities are demonstrated on several test problems. In
      particular for parity and symmetry problems we evolve solutions, which are fully
      general with respect to the number of inputs. We also evolve scalable and modular
      weightless recurrent networks capable of autonomous learning in a simple generic
      classification task. The encoding is very flexible and we demonstrate this by
      evolving networks capable of learning via neuromodulation. Finally, we evolve
      modular solutions to the retina problem, for which another well known
      neuroevolution method-HyperNEAT-was previously shown to fail. The proposed
      encoding outperformed HyperNEAT and Cellular Encoding also in another experiment,
      in which certain connectivity patterns must be discovered between layers.
      Therefore we conclude the proposed encoding is an interesting and competitive
      approach to evolve networks.

PMID- 21957433
TI  - Embodied Gesture Processing: Motor-Based Integration of Perception and Action in
      Social Artificial Agents.
AB  - A close coupling of perception and action processes is assumed to play an
      important role in basic capabilities of social interaction, such as guiding
      attention and observation of others' behavior, coordinating the form and
      functions of behavior, or grounding the understanding of others' behavior in
      one's own experiences. In the attempt to endow artificial embodied agents with
      similar abilities, we present a probabilistic model for the integration of
      perception and generation of hand-arm gestures via a hierarchy of shared motor
      representations, allowing for combined bottom-up and top-down processing. Results
      from human-agent interactions are reported demonstrating the model's performance
      in learning, observation, imitation, and generation of gestures.

PMID- 21957434
TI  - Developing Prognosis Tools to Identify Learning Difficulties in Children Using
      Machine Learning Technologies.
AB  - The Mental Attributes Profiling System was developed in 2002 (Laouris and Makris,
      Proceedings of multilingual & cross-cultural perspectives on Dyslexia, Omni
      Shoreham Hotel, Washington, D.C, 2002), to provide a multimodal evaluation of the
      learning potential and abilities of young children's brains. The method is based
      on the assessment of non-verbal abilities using video-like interfaces and was
      compared to more established methodologies in (Papadopoulos, Laouris, Makris,
      Proceedings of IDA 54th annual conference, San Diego, 2003), such as the Wechsler
      Intelligence Scale for Children (Watkins et al., Psychol Sch 34(4):309-319,
      1997). To do so, various tests have been applied to a population of 134 children
      aged 7-12 years old. This paper addresses the issue of identifying a minimal set
      of variables that are able to accurately predict the learning abilities of a
      given child. The use of Machine Learning technologies to do this provides the
      advantage of making no prior assumptions about the nature of the data and
      eliminating natural bias associated with data processing carried out by humans.
      Kohonen's Self Organising Maps (Kohonen, Biol Cybern 43:59-69, 1982) algorithm is
      able to split a population into groups based on large and complex sets of
      observations. Once the population is split, the individual groups can then be
      probed for their defining characteristics providing insight into the rationale of
      the split. The characteristics identified form the basis of classification
      systems that are able to accurately predict which group an individual will belong
      to, using only a small subset of the tests available. The specifics of this
      methodology are detailed herein, and the resulting classification systems provide
      an effective tool to prognose the learning abilities of new subjects.

PMID- 21957435
TI  - Assessing Expectations: Towards a Toolbox for an Ethics of Emerging Technologies.
AB  - In recent years, several authors have argued that the desirability of novel
      technologies should be assessed early, when they are still emerging. Such an
      ethical assessment of emerging technologies is by definition focused on an
      elusive object. Usually promises, expectations, and visions of the technology are
      taken as a starting point. As Nordmann and Rip have pointed out in a recent
      article, however, ethicists should not take for granted the plausibility of such
      expectations and visions. In this paper, we explore how the quality of
      expectations on emerging technologies might be assessed when engaging in a
      reflection on the desirability of emerging technologies. We propose that an
      assessment of expectations' plausibility should focus on statements on
      technological feasibility, societal usability, and desirability of the expected
      technology. Whereas the feasibility statement and, to a lesser extent, the
      usability statements are frequently quite futuristic, the claims on desirability,
      by contrast, often display a conservative stance towards the future. Assessing
      the quality of expectations and visions on behalf of emerging technologies
      requires, then, a careful and well-directed use of both skepticism and
      imagination. We conclude with a brief overview of the tools and methods ethicists
      could use to assess claims made on behalf of emerging technologies and improve
      the ethical reflection on them.

PMID- 21957436
TI  - Entanglement of Imaging and Imagining of Nanotechnology.
AB  - Images, ranging from visualizations of the nanoscale to future visions, abound
      within and beyond the world of nanotechnology. Rather than the contrast between
      imaging, i.e. creating images that are understood as offering a view on what is
      out there, and imagining, i.e. creating images offering impressions of how the
      nanoscale could look like and images presenting visions of worlds that might be
      realized, it is the entanglement between imaging and imagining which is the key
      to understanding what images do. Three main arenas of entanglement of imag(in)ing
      and the tensions involved are discussed: production practices and use of
      visualizations of the nanoscale; imag(in)ing the future and the present; and
      entanglements of nanoscience and art. In these three arenas one sees struggles
      about which images might stand for nanotechnology, but also some stabilization of
      the entanglement of imag(in)ing, for example in established rules in the
      practices of visualizing the nanoscale. Three images have become iconic, through
      the combination of their wide reception and further circulation. All three, the
      IBM logo, the Foresight Institute's Nanogear image, and the so-called Nanolouse,
      depict actual or imagined technoscientific objects and are thus seen as
      representing technoscientific achievements - while marking out territory.

PMID- 21957438
TI  - Genomic risk profiling of ischemic stroke: results of an international genome
      wide association meta-analysis.
AB  - INTRODUCTION: Familial aggregation of ischemic stroke derives from shared genetic
      and environmental factors. We present a meta-analysis of genome-wide association
      scans (GWAS) from 3 cohorts to identify the contribution of common variants to
      ischemic stroke risk. METHODS: This study involved 1464 ischemic stroke cases and
      1932 controls. Cases were genotyped using the Illumina 610 or 660 genotyping
      arrays; controls, with Illumina HumanHap 550Kv1 or 550Kv3 genotyping arrays.
      Imputation was performed with the 1000 Genomes European ancestry haplotypes
      (August 2010 release) as a reference. A total of 5,156,597 single-nucleotide
      polymorphisms (SNPs) were incorporated into the fixed effects meta-analysis. All
      SNPs associated with ischemic stroke (P<1*10(-5)) were incorporated into a
      multivariate risk profile model. RESULTS: No SNP reached genome-wide significance
      for ischemic stroke (P<5*10(-8)). Secondary analysis identified a significant
      cumulative effect for age at onset of stroke (first versus fifth quintile of
      cumulative profiles based on SNPs associated with late onset, beta = 14.77
      [10.85,18.68], P = 5.5*10(-12)), as well as a strong effect showing increased
      risk across samples with a high propensity for stroke among samples with enriched
      counts of suggestive risk alleles (P<5*10(-6)). Risk profile scores based only on
      genomic information offered little incremental prediction. DISCUSSION: There is
      little evidence of a common genetic variant contributing to moderate risk of
      ischemic stroke. Quintiles based on genetic loading of alleles associated with a
      younger age at onset of ischemic stroke revealed a significant difference in age
      at onset between those in the upper and lower quintiles. Using common variants
      from GWAS and imputation, genomic profiling remains inferior to family history of
      stroke for defining risk. Inclusion of genomic (rare variant) information may be
      required to improve clinical risk profiling.

PMID- 21957439
TI  - The transmembrane adaptor protein SIT inhibits TCR-mediated signaling.
AB  - Transmembrane adaptor proteins (TRAPs) organize signaling complexes at the plasma
      membrane, and thus function as critical linkers and integrators of signaling
      cascades downstream of antigen receptors. We have previously shown that the
      transmembrane adaptor protein SIT regulates the threshold for thymocyte
      selection. Moreover, T cells from SIT-deficient mice are hyperresponsive to CD3
      stimulation and undergo enhanced lymphopenia-induced homeostatic proliferation,
      thus indicating that SIT inhibits TCR-mediated signaling. Here, we have further
      addressed how SIT regulates signaling cascades in T cells. We demonstrate that
      the loss of SIT enhances TCR-mediated Akt activation and increased
      phosphorylation/inactivation of Foxo1, a transcription factor of the Forkhead
      family that inhibits cell cycle progression and regulates T-cell homeostasis. We
      have also shown that CD4(+) T cells from SIT-deficient mice display increased
      CD69 and CD40L expression indicating an altered activation status. Additional
      biochemical analyses further revealed that suppression of SIT expression by RNAi
      in human T cells resulted in an enhanced proximal TCR signaling. In summary, the
      data identify SIT as an important modulator of TCR-mediated signaling that
      regulates T-cell activation, homeostasis and tolerance.

PMID- 21957440
TI  - The neurotropic parasite Toxoplasma gondii increases dopamine metabolism.
AB  - The highly prevalent parasite Toxoplasma gondii manipulates its host's behavior.
      In infected rodents, the behavioral changes increase the likelihood that the
      parasite will be transmitted back to its definitive cat host, an essential step
      in completion of the parasite's life cycle. The mechanism(s) responsible for
      behavioral changes in the host is unknown but two lines of published evidence
      suggest that the parasite alters neurotransmitter signal transduction: the
      disruption of the parasite-induced behavioral changes with medications used to
      treat psychiatric disease (specifically dopamine antagonists) and identification
      of a tyrosine hydroxylase encoded in the parasite genome. In this study,
      infection of mammalian dopaminergic cells with T. gondii enhanced the levels of
      K+-induced release of dopamine several-fold, with a direct correlation between
      the number of infected cells and the quantity of dopamine released.
      Immunostaining brain sections of infected mice with dopamine antibody showed
      intense staining of encysted parasites. Based on these analyses, T. gondii
      orchestrates a significant increase in dopamine metabolism in neural cells.
      Tyrosine hydroxylase, the rate-limiting enzyme for dopamine synthesis, was also
      found in intracellular tissue cysts in brain tissue with antibodies specific for
      the parasite-encoded tyrosine hydroxylase. These observations provide a mechanism
      for parasite-induced behavioral changes. The observed effects on dopamine
      metabolism could also be relevant in interpreting reports of psychobehavioral
      changes in toxoplasmosis-infected humans.

PMID- 21957441
TI  - Visual working memory capacity does not modulate the feature-based information
      filtering in visual working memory.
AB  - BACKGROUND: The limited capacity of visual working memory (VWM) requires us to
      select the task relevant information and filter out the irrelevant information
      efficiently. Previous studies showed that the individual differences in VWM
      capacity dramatically influenced the way we filtered out the distracters
      displayed in distinct spatial-locations: low-capacity individuals were poorer at
      filtering them out than the high-capacity ones. However, when the target and
      distracting information pertain to the same object (i.e., multiple-featured
      object), whether the VWM capacity modulates the feature-based filtering remains
      unknown. METHODOLOGY/PRINCIPAL FINDINGS: We explored this issue mainly based on
      one of our recent studies, in which we asked the participants to remember three
      colors of colored-shapes or colored-landolt-Cs while using two types of task
      irrelevant information. We found that the irrelevant high-discriminable
      information could not be filtered out during the extraction of VWM but the
      irrelevant fine-grained information could be. We added 8 extra participants to
      the original 16 participants and then split the overall 24 participants into low-
      and high-VWM capacity groups. We found that regardless of the VWM capacity, the
      irrelevant high-discriminable information was selected into VWM, whereas the
      irrelevant fine-grained information was filtered out. The latter finding was
      further corroborated in a second experiment in which the participants were
      required to remember one colored-landolt-C and a more strict control was exerted
      over the VWM capacity. CONCLUSIONS/SIGNIFICANCE: We conclude that VWM capacity
      did not modulate the feature-based filtering in VWM.

PMID- 21957442
TI  - Early life stress enhancement of limbic epileptogenesis in adult rats:
      mechanistic insights.
AB  - BACKGROUND: Exposure to early postnatal stress is known to hasten the progression
      of kindling epileptogenesis in adult rats. Despite the significance of this for
      understanding mesial temporal lobe epilepsy (MTLE) and its associated
      psychopathology, research findings regarding underlying mechanisms are sparse. Of
      several possibilities, one important candidate mechanism is early life
      'programming' of the hypothalamic-pituitary-adrenal (HPA) axis by postnatal
      stress. Elevated corticosterone (CORT) in turn has consequences for neurogenesis
      and cell death relevant to epileptogenesis. Here we tested the hypotheses that MS
      would augment seizure-related corticosterone (CORT) release and enhance
      neuroplastic changes in the hippocampus. METHODOLOGY/PRINCIPAL FINDINGS: Eight
      week old Wistar rats, previously exposed on postnatal days 2-14 to either
      maternal separation stress (MS) or control brief early handling (EH), underwent
      rapid amygdala kindling. We measured seizure-induced serum CORT levels and post
      kindling neurogenesis (using BrdU). Three weeks post-kindling, rats were
      euthanized for histology of the hippocampal CA3c region (pyramidal cell counts)
      and dentate gyrus (DG) (to count BrdU-labelled cells and measure mossy fibre
      sprouting). As in our previous studies, rats exposed to MS had accelerated
      kindling rates in adulthood. Female MS rats had heightened CORT responses during
      and after kindling (p<0.05), with a similar trend in males. In both sexes total
      CA3c pyramidal cell numbers were reduced in MS vs. EH rats post-kindling (p =
      0.002). Dentate granule cell neurogenesis in female rats was significantly
      increased post-kindling in MS vs. EH rats. CONCLUSIONS/SIGNIFICANCE: These data
      demonstrate that early life stress results in enduring enhancement of HPA axis
      responses to limbic seizures, with increased hippocampal CA3c cell loss and
      augmented neurogenesis, in a sex-dependent pattern. This implicates important
      candidate mechanisms through which early life stress may promote vulnerability to
      limbic epileptogenesis in rats as well as to human MTLE and its associated
      psychiatric disorders.

PMID- 21957443
TI  - Structure-based development of small molecule PFKFB3 inhibitors: a framework for
      potential cancer therapeutic agents targeting the Warburg effect.
AB  - Cancer cells adopt glycolysis as the major source of metabolic energy production
      for fast cell growth. The HIF-1-induced PFKFB3 plays a key role in this
      adaptation by elevating the concentration of Fru-2,6-BP, the most potent
      glycolysis stimulator. As this metabolic conversion has been suggested to be a
      hallmark of cancer, PFKFB3 has emerged as a novel target for cancer chemotherapy.
      Here, we report that a small molecular inhibitor, N4A, was identified as an
      initial lead compound for PFKFB3 inhibitor with therapeutic potential. In an
      attempt to improve its potency, we determined the crystal structure of the
      PFKFB3*N4A complex to 2.4 A resolution and, exploiting the resulting molecular
      information, attained the more potent YN1. When tested on cultured cancer cells,
      both N4A and YN1 inhibited PFKFB3, suppressing the Fru-2,6-BP level, which in
      turn suppressed glycolysis and, ultimately, led to cell death. This study
      validates PFKFB3 as a target for new cancer therapies and provides a framework
      for future development efforts.

PMID- 21957444
TI  - The receptor tyrosine kinase FGFR2b/KGFR controls early differentiation of human
      keratinocytes.
AB  - The FGFRs trigger divergent responses, such as proliferation and differentiation,
      and the cell type as well as the context-dependent signaling are crucial for the
      functional outcome. The FGFR2b/KGFR is expressed exclusively on epithelial cells
      and plays a key role in skin homeostasis. Here we analyzed in vitro the role of
      KGFR in the early differentiation of keratinocytes modulating its expression by
      KGFR cDNA transient transfection or KGFR siRNA microinjection and inducing a
      synchronous wave of differentiation in pre-confluent cells. Immunofluorescence,
      biochemical and molecular approaches demonstrated that KGFR overexpression
      increased the early differentiation marker keratin 1 at both transcriptional and
      translational levels, while receptor depletion reduced it. Ligand-dependent
      receptor activation and signaling were required for this differentiative effect.
      Overexpression of kinase negative KGFR mutant or Tyr769 KGFR signaling mutant,
      which is not able to recruit and activate PLC-gamma, showed that the receptor
      kinase activity, but not its PLCgamma-mediated signaling, is required for
      differentiation. Reduction of K1 expression, obtained by AKT inhibition,
      demonstrated that the PI3K/Akt signaling pathway is involved in the control of
      KGFR-mediated keratinocyte differentiation. This in vitro experimental model
      indicates that FGFR2b/KGFR expression represents a key event regulating
      keratinocyte early differentiation during the switch from undifferentiated to
      differentiating cells.

PMID- 21957445
TI  - MexEF-OprN efflux pump exports the Pseudomonas quinolone signal (PQS) precursor
      HHQ (4-hydroxy-2-heptylquinoline).
AB  - Bacterial cells have evolved the capacity to communicate between each other via
      small diffusible chemical signals termed autoinducers. Pseudomonas aeruginosa is
      an opportunistic pathogen involved, among others, in cystic fibrosis
      complications. Virulence of P. aeruginosa relies on its ability to produce a
      number of autoinducers, including 4-hydroxy-2-alkylquinolines (HAQ). In a cell
      density-dependent manner, accumulated signals induce the expression of multiple
      targets, especially virulence factors. This phenomenon, called quorum sensing,
      promotes bacterial capacity to cause disease. Furthermore, P. aeruginosa
      possesses many multidrug efflux pumps conferring adaptive resistance to
      antibiotics. Activity of some of these efflux pumps also influences quorum
      sensing. The present study demonstrates that the MexEF-OprN efflux pump modulates
      quorum sensing through secretion of a signalling molecule belonging to the HAQ
      family. Moreover, activation of MexEF-OprN reduces virulence factor expression
      and swarming motility. Since MexEF-OprN can be activated in infected hosts even
      in the absence of antibiotic selective pressure, it could promote establishment
      of chronic infections in the lungs of people suffering from cystic fibrosis, thus
      diminishing the immune response to virulence factors. Therapeutic drugs that
      affect multidrug efflux pumps and HAQ-mediated quorum sensing would be valuable
      tools to shut down bacterial virulence.

PMID- 21957446
TI  - Intrinsic determinants of Abeta(12-24) pH-dependent self-assembly revealed by
      combined computational and experimental studies.
AB  - The propensity of amyloid-beta (Abeta) peptide to self-assemble into highly
      ordered amyloid structures lies at the core of their accumulation in the brain
      during Alzheimer's disease. By using all-atom explicit solvent replica exchange
      molecular dynamics simulations, we elucidated at the atomic level the intrinsic
      determinants of the pH-dependent dimerization of the central hydrophobic segment
      Abeta(12-24) and related these with the propensity to form amyloid fibrils
      measured by experimental tools such as atomic force microscopy and fluorescence.
      The process of Abeta(12-24) dimerization was evaluated in terms of free energy
      landscape, side-chain two-dimensional contact probability maps, beta-sheet
      registries, potential mean force as a function of inter-chain distances,
      secondary structure development and radial solvation distributions. We showed
      that dimerization is a key event in Abeta(12-24) amyloid formation; it is highly
      prompted in the order of pH 5.0>2.9>>8.4 and determines further amyloid growth.
      The dimerization is governed by a dynamic interplay of hydrophobic, electrostatic
      and solvation interactions permitting some variability of beta-sheets at each pH.
      These results provide atomistic insight into the complex process of molecular
      recognition detrimental for amyloid growth and pave the way for better
      understanding of the molecular basis of amyloid diseases.

PMID- 21957447
TI  - Observations of fallout from the Fukushima reactor accident in San Francisco Bay
      area rainwater.
AB  - We have observed fallout from the recent Fukushima Dai-ichi reactor accident in
      samples of rainwater collected in the San Francisco Bay area. Gamma ray spectra
      measured from these samples show clear evidence of fission products--(131,132)I,
      (132)Te, and (134,137)Cs. The activity levels we have measured for these isotopes
      are very low and pose no health risk to the public.

PMID- 21957449
TI  - How reproductive ecology contributes to the spread of a globally invasive fish.
AB  - Invasive freshwater fish represent a major threat to biodiversity. Here, we first
      demonstrate the dramatic, human-mediated range expansion of the Trinidadian guppy
      (Poecilia reticulata), an invasive fish with a reputation for negatively
      impacting native freshwater communities. Next, we explore possible mechanisms
      that might explain successful global establishment of this species. Guppies,
      along with some other notable invasive fish species such as mosquitofish
      (Gambusia spp.), have reproductive adaptations to ephemeral habitats that may
      enable introductions of very small numbers of founders to succeed. The remarkable
      ability of single pregnant guppies to routinely establish viable populations is
      demonstrated using a replicated mesocosm set up. In 86% of cases, these
      populations persisted for two years (the duration of the experiment).
      Establishment success was independent of founder origin (high and low predation
      habitats), and there was no loss of behavioural performance amongst mesocosm
      juveniles. Behavioural "signatures" of the founding locality were, however,
      evident in mesocosm fish. Our results demonstrate that introductions consisting
      of a single individual can lead to thriving populations of this invasive fish and
      suggest that particular caution should be exercised when introducing this
      species, or other livebearers, to natural water bodies.

PMID- 21957448
TI  - Neuronal deletion of caspase 8 protects against brain injury in mouse models of
      controlled cortical impact and kainic acid-induced excitotoxicity.
AB  - BACKGROUND: Acute brain injury is an important health problem. Given the critical
      position of caspase 8 at the crossroads of cell death pathways, we generated a
      new viable mouse line (Ncasp8(-/-)), in which the gene encoding caspase 8 was
      selectively deleted in neurons by cre-lox system. METHODOLOGY/PRINCIPAL FINDINGS:
      Caspase 8 deletion reduced rates of neuronal cell death in primary neuronal
      cultures and in whole brain organotypic coronal slice cultures prepared from 4
      and 8 month old mice and cultivated up to 14 days in vitro. Treatments of
      cultures with recombinant murine TNFalpha (100 ng/ml) or TRAIL (250 ng/mL) plus
      cyclohexamide significantly protected neurons against cell death induced by these
      apoptosis-inducing ligands. A protective role of caspase 8 deletion in vivo was
      also demonstrated using a controlled cortical impact (CCI) model of traumatic
      brain injury (TBI) and seizure-induced brain injury caused by kainic acid (KA).
      Morphometric analyses were performed using digital imaging in conjunction with
      image analysis algorithms. By employing virtual images of hundreds of brain
      sections, we were able to perform quantitative morphometry of histological and
      immunohistochemical staining data in an unbiased manner. In the TBI model,
      homozygous deletion of caspase 8 resulted in reduced lesion volumes, improved
      post-injury motor performance, superior learning and memory retention, decreased
      apoptosis, diminished proteolytic processing of caspases and caspase substrates,
      and less neuronal degeneration, compared to wild type, homozygous cre, and
      caspase 8-floxed control mice. In the KA model, Ncasp8(-/-) mice demonstrated
      superior survival, reduced seizure severity, less apoptosis, and reduced caspase
      3 processing. Uninjured aged knockout mice showed improved learning and memory,
      implicating a possible role for caspase 8 in cognitive decline with aging.
      CONCLUSIONS: Neuron-specific deletion of caspase 8 reduces brain damage and
      improves post-traumatic functional outcomes, suggesting an important role for
      this caspase in pathophysiology of acute brain trauma.

PMID- 21957450
TI  - Identification of Rothia bacteria as gluten-degrading natural colonizers of the
      upper gastro-intestinal tract.
AB  - BACKGROUND: Gluten proteins, prominent constituents of barley, wheat and rye,
      cause celiac disease in genetically predisposed subjects. Gluten is notoriously
      difficult to digest by mammalian proteolytic enzymes and the protease-resistant
      domains contain multiple immunogenic epitopes. The aim of this study was to
      identify novel sources of gluten-digesting microbial enzymes from the upper
      gastro-intestinal tract with the potential to neutralize gluten epitopes.
      METHODOLOGY/PRINCIPAL FINDINGS: Oral microorganisms with gluten-degrading
      capacity were obtained by a selective plating strategy using gluten agar.
      Microbial speciations were carried out by 16S rDNA gene sequencing. Enzyme
      activities were assessed using gliadin-derived enzymatic substrates, gliadins in
      solution, gliadin zymography, and 33-mer alpha-gliadin and 26-mer gamma-gliadin
      immunogenic peptides. Fragments of the gliadin peptides were separated by RP-HPLC
      and structurally characterized by mass spectrometry. Strains with high activity
      towards gluten were typed as Rothia mucilaginosa and Rothia aeria. Gliadins (250
      ug/ml) added to Rothia cell suspensions (OD(620) 1.2) were degraded by 50% after
      ~30 min of incubation. Importantly, the 33-mer and 26-mer immunogenic peptides
      were also cleaved, primarily C-terminal to Xaa-Pro-Gln (XPQ) and Xaa-Pro-Tyr
      (XPY). The major gliadin-degrading enzymes produced by the Rothia strains were
      ~70-75 kDa in size, and the enzyme expressed by Rothia aeria was active over a
      wide pH range (pH 3-10). CONCLUSION/SIGNIFICANCE: While the human digestive
      enzyme system lacks the capacity to cleave immunogenic gluten, such activities
      are naturally present in the oral microbial enzyme repertoire. The identified
      bacteria may be exploited for physiologic degradation of harmful gluten peptides.

PMID- 21957451
TI  - Projected evolution of California's San Francisco Bay-Delta-river system in a
      century of climate change.
AB  - BACKGROUND: Accumulating evidence shows that the planet is warming as a response
      to human emissions of greenhouse gases. Strategies of adaptation to climate
      change will require quantitative projections of how altered regional patterns of
      temperature, precipitation and sea level could cascade to provoke local impacts
      such as modified water supplies, increasing risks of coastal flooding, and
      growing challenges to sustainability of native species. METHODOLOGY/PRINCIPAL
      FINDINGS: We linked a series of models to investigate responses of California's
      San Francisco Estuary-Watershed (SFEW) system to two contrasting scenarios of
      climate change. Model outputs for scenarios of fast and moderate warming are
      presented as 2010-2099 projections of nine indicators of changing climate,
      hydrology and habitat quality. Trends of these indicators measure rates of:
      increasing air and water temperatures, salinity and sea level; decreasing
      precipitation, runoff, snowmelt contribution to runoff, and suspended sediment
      concentrations; and increasing frequency of extreme environmental conditions such
      as water temperatures and sea level beyond the ranges of historical observations.
      CONCLUSIONS/SIGNIFICANCE: Most of these environmental indicators change
      substantially over the 21(st) century, and many would present challenges to
      natural and managed systems. Adaptations to these changes will require flexible
      planning to cope with growing risks to humans and the challenges of meeting
      demands for fresh water and sustaining native biota. Programs of ecosystem
      rehabilitation and biodiversity conservation in coastal landscapes will be most
      likely to meet their objectives if they are designed from considerations that
      include: (1) an integrated perspective that river-estuary systems are influenced
      by effects of climate change operating on both watersheds and oceans; (2) varying
      sensitivity among environmental indicators to the uncertainty of future climates;
      (3) inevitability of biological community changes as responses to cumulative
      effects of climate change and other drivers of habitat transformations; and (4)
      anticipation and adaptation to the growing probability of ecosystem regime
      shifts.

PMID- 21957452
TI  - Natural killer cell mediated cytotoxic responses in the Tasmanian devil.
AB  - The Tasmanian devil (Sarcophilus harrisii), the world's largest marsupial
      carnivore, is under threat of extinction following the emergence of an infectious
      cancer. Devil facial tumour disease (DFTD) is spread between Tasmanian devils
      during biting. The disease is consistently fatal and devils succumb without
      developing a protective immune response. The aim of this study was to determine
      if Tasmanian devils were capable of forming cytotoxic antitumour responses and
      develop antibodies against DFTD cells and foreign tumour cells. The two Tasmanian
      devils immunised with irradiated DFTD cells did not form cytotoxic or humoral
      responses against DFTD cells, even after multiple immunisations. However,
      following immunisation with xenogenic K562 cells, devils did produce cytotoxic
      responses and antibodies against this foreign tumour cell line. The cytotoxicity
      appeared to occur through the activity of natural killer (NK) cells in an
      antibody dependent manner. Classical NK cell responses, such as innate killing of
      DFTD and foreign cancer cells, were not observed. Cells with an NK-like phenotype
      comprised approximately 4 percent of peripheral blood mononuclear cells. The
      results of this study suggest that Tasmanian devils have NK cells with functional
      cytotoxic pathways. Although devil NK cells do not directly recognise DFTD cancer
      cells, the development of antibody dependent cell-mediated cytotoxicity presents
      a potential pathway to induce cytotoxic responses against the disease. These
      findings have positive implications for future DFTD vaccine research.

PMID- 21957453
TI  - Do women's voices provide cues of the likelihood of ovulation? The importance of
      sampling regime.
AB  - The human voice provides a rich source of information about individual attributes
      such as body size, developmental stability and emotional state. Moreover, there
      is evidence that female voice characteristics change across the menstrual cycle.
      A previous study reported that women speak with higher fundamental frequency (F0)
      in the high-fertility compared to the low-fertility phase. To gain further
      insights into the mechanisms underlying this variation in perceived
      attractiveness and the relationship between vocal quality and the timing of
      ovulation, we combined hormone measurements and acoustic analyses, to
      characterize voice changes on a day-to-day basis throughout the menstrual cycle.
      Voice characteristics were measured from free speech as well as sustained vowels.
      In addition, we asked men to rate vocal attractiveness from selected samples. The
      free speech samples revealed marginally significant variation in F0 with an
      increase prior to and a distinct drop during ovulation. Overall variation
      throughout the cycle, however, precluded unequivocal identification of the period
      with the highest conception risk. The analysis of vowel samples revealed a
      significant increase in degree of unvoiceness and noise-to-harmonic ratio during
      menstruation, possibly related to an increase in tissue water content. Neither
      estrogen nor progestogen levels predicted the observed changes in acoustic
      characteristics. The perceptual experiments revealed a preference by males for
      voice samples recorded during the pre-ovulatory period compared to other periods
      in the cycle. While overall we confirm earlier findings in that women speak with
      a higher and more variable fundamental frequency just prior to ovulation, the
      present study highlights the importance of taking the full range of variation
      into account before drawing conclusions about the value of these cues for the
      detection of ovulation.

PMID- 21957454
TI  - A trigeminoreticular pathway: implications in pain.
AB  - Neurons in the caudalmost ventrolateral medulla (cmVLM) respond to noxious
      stimulation. We previously have shown most efferent projections from this locus
      project to areas implicated either in the processing or modulation of pain. Here
      we show the cmVLM of the rat receives projections from superficial laminae of the
      medullary dorsal horn (MDH) and has neurons activated with capsaicin injections
      into the temporalis muscle. Injections of either biotinylated dextran amine (BDA)
      into the MDH or fluorogold (FG)/fluorescent microbeads into the cmVLM showed
      projections from lamina I and II of the MDH to the cmVLM. Morphometric analysis
      showed the retrogradely-labeled neurons were small (area 88.7 um(2)+/-3.4) and
      mostly fusiform in shape. Injections (20-50 ul) of 0.5% capsaicin into the
      temporalis muscle and subsequent immunohistochemistry for c-Fos showed nuclei
      labeled in the dorsomedial trigeminocervical complex (TCC), the cmVLM, the
      lateral medulla, and the internal lateral subnucleus of the parabrachial complex
      (PBil). Additional labeling with c-Fos was seen in the subnucleus interpolaris of
      the spinal trigeminal nucleus, the rostral ventrolateral medulla, the superior
      salivatory nucleus, the rostral ventromedial medulla, and the A1, A5, A7 and
      subcoeruleus catecholamine areas. Injections of FG into the PBil produced robust
      label in the lateral medulla and cmVLM while injections of BDA into the lateral
      medulla showed projections to the PBil. Immunohistochemical experiments to
      antibodies against substance P, the substance P receptor (NK1), calcitonin gene
      regulating peptide, leucine enkephalin, VRL1 (TPRV2) receptors and neuropeptide Y
      showed that these peptides/receptors densely stained the cmVLM. We suggest the
      MDH- cmVLM projection is important for pain from head and neck areas. We offer a
      potential new pathway for regulating deep pain via the neurons of the TCC, the
      cmVLM, the lateral medulla, and the PBil and propose these areas compose a
      trigeminoreticular pathway, possibly the trigeminal homologue of the
      spinoreticulothalamic pathway.

PMID- 21957455
TI  - Natural form of noncytolytic flexible human Fc as a long-acting carrier of
      agonistic ligand, erythropoietin.
AB  - Human IgG1 Fc has been widely used as a bioconjugate, but exhibits shortcomings,
      such as antibody- and complement-mediated cytotoxicity as well as decreased
      bioactivity, when applied to agonistic proteins. Here, we constructed a
      nonimmunogenic, noncytolytic and flexible hybrid Fc (hyFc) consisting of IgD and
      IgG4, and tested its function using erythropoietin (EPO) conjugate, EPO-hyFc.
      Despite low amino acid homology (20.5%) between IgD Fc and IgG4 Fc, EPO-hyFc
      retained "Y-shaped" structure and repeated intravenous administrations of EPO
      hyFc into monkeys did not generate EPO-hyFc-specific antibody responses.
      Furthermore, EPO-hyFc could not bind to FcgammaR I and C1q in contrast to EPO
      IgG1 Fc. In addition, EPO-hyFc exhibited better in vitro bioactivity and in vivo
      bioactivity in rats than EPO-IgG1 Fc, presumably due to the high flexibility of
      IgD. Moreover, the mean serum half-life of EPO-hyFc(H), a high sialic acid
      content form of EPO-hyFc, was approximately 2-fold longer than that of the
      heavily glycosylated EPO, darbepoetin alfa, in rats. More importantly,
      subcutaneous injection of EPO-hyFc(H) not only induced a significantly greater
      elevation of serum hemoglobin levels than darbepoetin alfa in both normal rats
      and cisplatin-induced anemic rats, but also displayed a delayed time to maximal
      serum level and twice final area-under-the-curve (AUC(last)). Taken together,
      hyFc might be a more attractive Fc conjugate for agonistic proteins/peptides than
      IgG1 Fc due to its capability to elongate their half-lives without inducing host
      effector functions and hindering bioactivity of fused molecules. Additionally, a
      head-to-head comparison demonstrated that hyFc-fusion strategy more effectively
      improved the in vivo bioactivity of EPO than the hyperglycosylation approach.

PMID- 21957456
TI  - Functional heterogeneity of breast fibroblasts is defined by a prostaglandin
      secretory phenotype that promotes expansion of cancer-stem like cells.
AB  - Fibroblasts are important in orchestrating various functions necessary for
      maintaining normal tissue homeostasis as well as promoting malignant tumor
      growth. Significant evidence indicates that fibroblasts are functionally
      heterogeneous with respect to their ability to promote tumor growth, but markers
      that can be used to distinguish growth promoting from growth suppressing
      fibroblasts remain ill-defined. Here we show that human breast fibroblasts are
      functionally heterogeneous with respect to tumor-promoting activity regardless of
      whether they were isolated from normal or cancerous breast tissues. Rather than
      significant differences in fibroblast marker expression, we show that fibroblasts
      secreting abundant levels of prostaglandin (PGE2), when isolated from either
      reduction mammoplasty or carcinoma tissues, were both capable of enhancing tumor
      growth in vivo and could increase the number of cancer stem-like cells. PGE2
      further enhanced the tumor promoting properties of fibroblasts by increasing
      secretion of IL-6, which was necessary, but not sufficient, for expansion of
      breast cancer stem-like cells. These findings identify a population of
      fibroblasts which both produce and respond to PGE2, and that are functionally
      distinct from other fibroblasts. Identifying markers of these cells could allow
      for the targeted ablation of tumor-promoting and inflammatory fibroblasts in
      human breast cancers.

PMID- 21957457
TI  - The spread of inequality.
AB  - The causes of socioeconomic inequality have been debated since the time of Plato.
      Many reasons for the development of stratification have been proposed, from the
      need for hierarchical control over large-scale irrigation systems to the
      accumulation of small differences in wealth over time via inheritance processes.
      However, none of these explains how unequal societies came to completely displace
      egalitarian cultural norms over time. Our study models demographic consequences
      associated with the unequal distribution of resources in stratified societies.
      Agent-based simulation results show that in constant environments, unequal access
      to resources can be demographically destabilizing, resulting in the outward
      migration and spread of such societies even when population size is relatively
      small. In variable environments, stratified societies spread more and are also
      better able to survive resource shortages by sequestering mortality in the lower
      classes. The predictions of our simulation are provided modest support by a range
      of existing empirical studies. In short, the fact that stratified societies today
      vastly outnumber egalitarian societies may not be due to the transformation of
      egalitarian norms and structures, but may instead reflect the more rapid
      migration of stratified societies and consequent conquest or displacement of
      egalitarian societies over time.

PMID- 21957458
TI  - A new way to measure the world's protected area coverage.
AB  - Protected areas are effective at stopping biodiversity loss, but their placement
      is constrained by the needs of people. Consequently protected areas are often
      biased toward areas that are unattractive for other human uses. Current reporting
      metrics that emphasise the total area protected do not account for this bias. To
      address this problem we propose that the distribution of protected areas be
      evaluated with an economic metric used to quantify inequality in income--the Gini
      coefficient. Using a modified version of this measure we discover that 73% of
      countries have inequitably protected their biodiversity and that common measures
      of protected area coverage do not adequately reveal this bias. Used in
      combination with total percentage protection, the Gini coefficient will improve
      the effectiveness of reporting on the growth of protected area coverage, paving
      the way for better representation of the world's biodiversity.

PMID- 21957460
TI  - Implications of advancing paternal age: does it affect offspring school
      performance?
AB  - Average paternal age is increasing in many high income countries, but the
      implications of this demographic shift for child health and welfare are poorly
      understood. There is equivocal evidence that children of older fathers are at
      increased risk of neurodevelopmental disorders and reduced IQ. We therefore
      report here on the relationship between paternal age and a composite indicator of
      scholastic achievement during adolescence, i.e. compulsory school leaving grades,
      among recent birth cohorts in Stockholm County where delayed paternity is notably
      common. We performed a record-linkage study comprising all individuals in
      Stockholm County who finished 9 years of compulsory school from 2000 through 2007
      (n = 155,875). Data on school leaving grades and parental characteristics were
      retrieved from administrative and health service registers and analyzed using
      multiple linear regression. Advancing paternal age at birth was not associated
      with a decrease in school leaving grades in adolescent offspring. After
      adjustment for year of graduation, maternal age and parental education, country
      of birth and parental mental health service use, offspring of fathers aged 50
      years or older had on average 0.3 (95% CI -3.8, 4.4) points higher grades than
      those of fathers aged 30-34 years. In conclusion, advancing paternal age is not
      associated with poorer school performance in adolescence. Adverse effects of
      delayed paternity on offspring cognitive function, if any, may be counterbalanced
      by other potential advantages for children born to older fathers.

PMID- 21957459
TI  - Dynamic gut microbiome across life history of the malaria mosquito Anopheles
      gambiae in Kenya.
AB  - The mosquito gut represents an ecosystem that accommodates a complex, intimately
      associated microbiome. It is increasingly clear that the gut microbiome
      influences a wide variety of host traits, such as fitness and immunity.
      Understanding the microbial community structure and its dynamics across mosquito
      life is a prerequisite for comprehending the symbiotic relationship between the
      mosquito and its gut microbial residents. Here we characterized gut bacterial
      communities across larvae, pupae and adults of Anopheles gambiae reared in semi
      natural habitats in Kenya by pyrosequencing bacterial 16S rRNA fragments.
      Immatures and adults showed distinctive gut community structures. Photosynthetic
      Cyanobacteria were predominant in the larval and pupal guts while Proteobacteria
      and Bacteroidetes dominated the adult guts, with core taxa of Enterobacteriaceae
      and Flavobacteriaceae. At the adult stage, diet regime (sugar meal and blood
      meal) significantly affects the microbial structure. Intriguingly, blood meals
      drastically reduced the community diversity and favored enteric bacteria.
      Comparative genomic analysis revealed that the enriched enteric bacteria possess
      large genetic redox capacity of coping with oxidative and nitrosative stresses
      that are associated with the catabolism of blood meal, suggesting a beneficial
      role in maintaining gut redox homeostasis. Interestingly, gut community structure
      was similar in the adult stage between the field and laboratory mosquitoes,
      indicating that mosquito gut is a selective eco-environment for its microbiome.
      This comprehensive gut metatgenomic profile suggests a concerted symbiotic
      genetic association between gut inhabitants and host.

PMID- 21957462
TI  - A prospective study of diet quality and mental health in adolescents.
AB  - OBJECTIVES: A number of cross-sectional and prospective studies have now been
      published demonstrating inverse relationships between diet quality and the common
      mental disorders in adults. However, there are no existing prospective studies of
      this association in adolescents, the onset period of most disorders, limiting
      inferences regarding possible causal relationships. METHODS: In this study, 3040
      Australian adolescents, aged 11-18 years at baseline, were measured in 2005-6 and
      2007-8. Information on diet and mental health was collected by self-report and
      anthropometric data by trained researchers. RESULTS: There were cross-sectional,
      dose response relationships identified between measures of both healthy
      (positive) and unhealthy (inverse) diets and scores on the emotional subscale of
      the Pediatric Quality of Life Inventory (PedsQL), where higher scores mean better
      mental health, before and after adjustments for age, gender, socio-economic
      status, dieting behaviours, body mass index and physical activity. Higher healthy
      diet scores at baseline also predicted higher PedsQL scores at follow-up, while
      higher unhealthy diet scores at baseline predicted lower PedsQL scores at follow
      up. Improvements in diet quality were mirrored by improvements in mental health
      over the follow-up period, while deteriorating diet quality was associated with
      poorer psychological functioning. Finally, results did not support the reverse
      causality hypothesis. CONCLUSION: This study highlights the importance of diet in
      adolescence and its potential role in modifying mental health over the life
      course. Given that the majority of common mental health problems first manifest
      in adolescence, intervention studies are now required to test the effectiveness
      of preventing the common mental disorders through dietary modification.

PMID- 21957461
TI  - A new thermosensitive smc-3 allele reveals involvement of cohesin in homologous
      recombination in C. elegans.
AB  - The cohesin complex is required for the cohesion of sister chromatids and for
      correct segregation during mitosis and meiosis. Crossover recombination, together
      with cohesion, is essential for the disjunction of homologous chromosomes during
      the first meiotic division. Cohesin has been implicated in facilitating
      recombinational repair of DNA lesions via the sister chromatid. Here, we made use
      of a new temperature-sensitive mutation in the Caenorhabditis elegans SMC-3
      protein to study the role of cohesin in the repair of DNA double-strand breaks
      (DSBs) and hence in meiotic crossing over. We report that attenuation of cohesin
      was associated with extensive SPO-11-dependent chromosome fragmentation, which is
      representative of unrepaired DSBs. We also found that attenuated cohesin likely
      increased the number of DSBs and eliminated the need of MRE-11 and RAD-50 for DSB
      formation in C. elegans, which suggests a role for the MRN complex in making
      cohesin-loaded chromatin susceptible to meiotic DSBs. Notably, in spite of
      largely intact sister chromatid cohesion, backup DSB repair via the sister
      chromatid was mostly impaired. We also found that weakened cohesins affected
      mitotic repair of DSBs by homologous recombination, whereas NHEJ repair was not
      affected. Our data suggest that recombinational DNA repair makes higher demands
      on cohesins than does chromosome segregation.

PMID- 21957463
TI  - Phylogenomic analysis of Odyssella thessalonicensis fortifies the common origin
      of Rickettsiales, Pelagibacter ubique and Reclimonas americana mitochondrion.
AB  - BACKGROUND: The evolution of the Alphaproteobacteria and origin of the
      mitochondria are topics of considerable debate. Most studies have placed the
      mitochondria ancestor within the Rickettsiales order. Ten years ago, the
      bacterium Odyssella thessalonicensis was isolated from Acanthamoeba spp., and the
      16S rDNA phylogeny placed it within the Rickettsiales. Recently, the whole genome
      of O. thessalonicensis has been sequenced, and 16S rDNA phylogeny and more robust
      and accurate phylogenomic analyses have been performed with 65 highly conserved
      proteins. METHODOLOGY/PRINCIPAL FINDINGS: The results suggested that the O.
      thessalonicensis emerged between the Rickettsiales and other Alphaproteobacteria.
      The mitochondrial proteins of the Reclinomonas americana have been used to locate
      the phylogenetic position of the mitochondrion ancestor within the
      Alphaproteobacteria tree. Using the K tree score method, nine mitochondrion
      encoded proteins, whose phylogenies were congruent with the Alphaproteobacteria
      phylogenomic tree, have been selected and concatenated for Bayesian and Maximum
      Likelihood phylogenies. The Reclinomonas americana mitochondrion is a sister
      taxon to the free-living bacteria Candidatus Pelagibacter ubique, and together,
      they form a clade that is deeply rooted in the Rickettsiales clade.
      CONCLUSIONS/SIGNIFICANCE: The Reclinomonas americana mitochondrion phylogenomic
      study confirmed that mitochondria emerged deeply in the Rickettsiales clade and
      that they are closely related to Candidatus Pelagibacter ubique.

PMID- 21957464
TI  - Fluid intelligence and psychosocial outcome: from logical problem solving to
      social adaptation.
AB  - BACKGROUND: While fluid intelligence has proved to be central to executive
      functioning, logical reasoning and other frontal functions, the role of this
      ability in psychosocial adaptation has not been well characterized.
      METHODOLOGY/PRINCIPAL FINDINGS: A random-probabilistic sample of 2370 secondary
      school students completed measures of fluid intelligence (Raven's Progressive
      Matrices, RPM) and several measures of psychological adaptation: bullying
      (Delaware Bullying Questionnaire), domestic abuse of adolescents (Conflict Tactic
      Scale), drug intake (ONUDD), self-esteem (Rosenberg's Self Esteem Scale) and the
      Perceived Mental Health Scale (Spanish adaptation). Lower fluid intelligence
      scores were associated with physical violence, both in the role of victim and
      victimizer. Drug intake, especially cannabis, cocaine and inhalants and lower
      self-esteem were also associated with lower fluid intelligence. Finally, scores
      on the perceived mental health assessment were better when fluid intelligence
      scores were higher. CONCLUSIONS/SIGNIFICANCE: Our results show evidence of a
      strong association between psychosocial adaptation and fluid intelligence,
      suggesting that the latter is not only central to executive functioning but also
      forms part of a more general capacity for adaptation to social contexts.

PMID- 21957465
TI  - Sensory experience differentially modulates the mRNA expression of the
      polysialyltransferases ST8SiaII and ST8SiaIV in postnatal mouse visual cortex.
AB  - Polysialic acid (PSA) is a unique carbohydrate composed of a linear homopolymer
      of alpha-2,8 linked sialic acid, and is mainly attached to the fifth
      immunoglobulin-like domain of the neural cell adhesion molecule (NCAM) in
      vertebrate neural system. In the brain, PSA is exclusively synthesized by the two
      polysialyltransferases ST8SiaII (also known as STX) and ST8SiaIV (also known as
      PST). By modulating adhesive property of NCAM, PSA plays a critical role in
      several neural development processes such as cell migration, neurite outgrowth,
      axon pathfinding, synaptogenesis and activity-dependent plasticity. The
      expression of PSA is temporally and spatially regulated during neural development
      and a tight regulation of PSA expression is essential to its biological function.
      In mouse visual cortex, PSA is downregulated following eye opening and its
      decrease allows the maturation of GABAergic synapses and the opening of the
      critical period for ocular dominance plasticity. Relatively little is known about
      how PSA levels are regulated by sensory experience and neuronal activity. Here,
      we demonstrate that while both ST8SiaII and ST8SiaIV mRNA levels decrease around
      the time of eye opening in mouse visual cortex, only ST8SiaII mRNA level
      reduction is regulated by sensory experience. Using an organotypic culture system
      from mouse visual cortex, we further show that ST8SiaII gene expression is
      regulated by spiking activity and NMDA-mediated excitation. Further, we show that
      both ST8SiaII and ST8SiaIV mRNA levels are positively regulated by PKC-mediated
      signaling. Therefore, sensory experience-dependent ST8SiaII gene expression
      regulates PSA levels in postnatal visual cortex, thus acting as molecular link
      between visual activity and PSA expression.

PMID- 21957466
TI  - Cardiac and respiratory patterns synchronize between persons during choir
      singing.
AB  - Dyadic and collective activities requiring temporally coordinated action are
      likely to be associated with cardiac and respiratory patterns that synchronize
      within and between people. However, the extent and functional significance of
      cardiac and respiratory between-person couplings have not been investigated thus
      far. Here, we report interpersonal oscillatory couplings among eleven singers and
      one conductor engaged in choir singing. We find that: (a) phase synchronization
      both in respiration and heart rate variability increase significantly during
      singing relative to a rest condition; (b) phase synchronization is higher when
      singing in unison than when singing pieces with multiple voice parts; (c)
      directed coupling measures are consistent with the presence of causal effects of
      the conductor on the singers at high modulation frequencies; (d) the different
      voices of the choir are reflected in network analyses of cardiac and respiratory
      activity based on graph theory. Our results suggest that oscillatory coupling of
      cardiac and respiratory patterns provide a physiological basis for interpersonal
      action coordination.

PMID- 21957467
TI  - Molecular characterization of the region 7q22.1 in splenic marginal zone
      lymphomas.
AB  - Splenic marginal zone lymphomas (SMZL) are an uncommon type of B-cell non
      Hodgkin's lymphoma (NHL-B) in which no specific chromosomal translocations have
      been described. In contrast, the most frequent cytogenetic abnormality is the
      loss of the long arm of chromosome 7 (7q). Previous reports have located this
      loss in the 7q32 region. In order to better characterize the genomic imbalances
      in SMZL, molecular studies were carried out in 73 patients with SMZL. To gain
      insight into the mapping at 7q a tiling array was also used. The results
      confirmed the loss of 7q as the most frequent change. In addition, several
      abnormalities, including 4q22.1, 1q21.3-q22, 6q25.3, 20q13.33, 3q28, 2q23.3-q24.1
      and 17p13, were also present. A loss of 7q22.1 at 99925039-101348479 bp was
      observed in half of the cases. The region of 7q22.1 has not previously been
      characterised in SMZL. Our results confirmed the presence of a new region of loss
      on chromosome 7 in these NHL.

PMID- 21957468
TI  - Characterization of the biosynthesis, processing and kinetic mechanism of action
      of the enzyme deficient in mucopolysaccharidosis IIIC.
AB  - Heparin acetyl-CoA:alpha-glucosaminide N-acetyltransferase (N-acetyltransferase,
      EC 2.3.1.78) is an integral lysosomal membrane protein containing 11
      transmembrane domains, encoded by the HGSNAT gene. Deficiencies of N
      acetyltransferase lead to mucopolysaccharidosis IIIC. We demonstrate that
      contrary to a previous report, the N-acetyltransferase signal peptide is co
      translationally cleaved and that this event is required for its intracellular
      transport to the lysosome. While we confirm that the N-acetyltransferase
      precursor polypeptide is processed in the lysosome into a small amino-terminal
      alpha- and a larger beta- chain, we further characterize this event by
      identifying the mature amino-terminus of each chain. We also demonstrate this
      processing step(s) is not, as previously reported, needed to produce a functional
      transferase, i.e., the precursor is active. We next optimize the biochemical
      assay procedure so that it remains linear as N-acetyltransferase is purified or
      protein-extracts containing N-acetyltransferase are diluted, by the inclusion of
      negatively charged lipids. We then use this assay to demonstrate that the
      purified single N-acetyltransferase protein is both necessary and sufficient to
      express transferase activity, and that N-acetyltransferase functions as a
      monomer. Finally, the kinetic mechanism of action of purified N-acetyltransferase
      was evaluated and found to be a random sequential mechanism involving the
      formation of a ternary complex with its two substrates; i.e., N-acetyltransferase
      does not operate through a ping-pong mechanism as previously reported. We confirm
      this conclusion by demonstrating experimentally that no acetylated enzyme
      intermediate is formed during the reaction.

PMID- 21957469
TI  - Incidence and severity of coronary artery disease in patients with atrial
      fibrillation undergoing first-time coronary angiography.
AB  - BACKGROUND: In standard reference sources, the incidence of coronary artery
      disease (CAD) in patients with atrial fibrillation (AF) ranged between 24 and
      46.5%. Since then, the incidence of cardiovascular risk factors (CRF) has
      increased and modern treatment strategies ("pill in the pocket") are only
      applicable to patients without structural heart disease. The aim of this study
      was to investigate the incidence and severity of CAD in patients with AF.
      METHODS: From January 2005 until December 2009, we included 261 consecutive
      patients admitted to hospital with paroxysmal, persistent or permanent AF in this
      prospective study. All patients underwent coronary angiography and the Framingham
      risk score (FRS) was calculated. Patients with previously diagnosed or previously
      excluded CAD were excluded. RESULTS: The overall incidence of CAD in patients
      presenting with AF was 34%; in patients >70 years, the incidence of CAD was 41%.
      The incidence of patients undergoing a percutaneous coronary intervention (PCI)
      or coronary artery bypass graft (CABG) was 21%. Patients with CAD were older
      (73+/-8 years vs 68+/-10 years, p = 0.001), had significantly more frequent
      hypercholesterolemia (60% vs 30%, p<0.001), were more frequent smokers (26% vs
      13%, p = 0.017) and suffered from angina more often (37% vs 2%, p<0.001). There
      was a significant linear trend among the FRS categories in percentage and the
      prevalence of CAD and PCI/CABG (p<0.0001). CONCLUSIONS: The overall incidence of
      CAD in patients presenting with AF was relatively high at 34%; the incidence of
      PCI/CABG was 21%. Based upon increasing CRF in the western world, we recommend a
      careful investigation respecting the FRS to either definitely exclude or
      establish an early diagnosis of CAD--which could contribute to an early and safe
      therapeutic strategy considering type Ic antiarrhythmics and oral
      anticoagulation.

PMID- 21957470
TI  - The developmental trajectory of brain-scalp distance from birth through
      childhood: implications for functional neuroimaging.
AB  - Measurements of human brain function in children are of increasing interest in
      cognitive neuroscience. Many techniques for brain mapping used in children,
      including functional near-infrared spectroscopy (fNIRS), electroencephalography
      (EEG), magnetoencephalography (MEG) and transcranial magnetic stimulation (TMS),
      use probes placed on or near the scalp. The distance between the scalp and the
      brain is a key variable for these techniques because optical, electrical and
      magnetic signals are attenuated by distance. However, little is known about how
      scalp-brain distance differs between different cortical regions in children or
      how it changes with development. We investigated scalp-brain distance in 71
      children, from newborn to age 12 years, using structural T1-weighted MRI scans of
      the whole head. Three-dimensional reconstructions were created from the scalp
      surface to allow for accurate calculation of brain-scalp distance. Nine brain
      landmarks in different cortical regions were manually selected in each subject
      based on the published fNIRS literature. Significant effects were found for age,
      cortical region and hemisphere. Brain-scalp distances were lowest in young
      children, and increased with age to up to double the newborn distance. There were
      also dramatic differences between brain regions, with up to 50% differences
      between landmarks. In frontal and temporal regions, scalp-brain distances were
      significantly greater in the right hemisphere than in the left hemisphere. The
      largest contributors to developmental changes in brain-scalp distance were
      increases in the corticospinal fluid (CSF) and inner table of the cranium. These
      results have important implications for functional imaging studies of children:
      age and brain-region related differences in fNIRS signals could be due to the
      confounding factor of brain-scalp distance and not true differences in brain
      activity.

PMID- 21957471
TI  - Odor-based recognition of familiar and related conspecifics: a first test
      conducted on captive Humboldt penguins (Spheniscus humboldti).
AB  - Studies of kin recognition in birds have largely focused on parent-offspring
      recognition using auditory or visual discrimination. Recent studies indicate that
      birds use odors during social and familial interactions and possibly for mate
      choice, suggesting olfactory cues may mediate kin recognition as well. Here, we
      show that Humboldt penguins (Spheniscus humboldti), a natally philopatric species
      with lifetime monogamy, discriminate between familiar and unfamiliar non-kin
      odors (using prior association) and between unfamiliar kin and non-kin odors
      (using phenotype matching). Penguins preferred familiar non-kin odors, which may
      be associated with the recognition of nest mates and colony mates and with
      locating burrows at night after foraging. In tests of kin recognition, penguins
      preferred unfamiliar non-kin odors. Penguins may have perceived non-kin odors as
      novel because they did not match the birds' recognition templates. Phenotype
      matching is likely the primary mechanism for kin recognition within the colony to
      avoid inbreeding. To our knowledge this is the first study to provide evidence of
      odor-based kin discrimination in a bird.

PMID- 21957472
TI  - Long-term cold acclimation extends survival time at 0 degrees C and modifies the
      metabolomic profiles of the larvae of the fruit fly Drosophila melanogaster.
AB  - BACKGROUND: Drosophila melanogaster is a chill-susceptible insect. Previous
      studies on this fly focused on acute direct chilling injury during cold shock and
      showed that lower lethal temperature (LLT, approximately -5 degrees C) exhibits
      relatively low plasticity and that acclimations, both rapid cold hardening (RCH)
      and long-term cold acclimation, shift the LLT by only a few degrees at the
      maximum. PRINCIPAL FINDINGS: We found that long-term cold acclimation
      considerably improved cold tolerance in fully grown third-instar larvae of D.
      melanogaster. A comparison of the larvae acclimated at constant 25 degrees C with
      those acclimated at constant 15 degrees C followed by constant 6 degrees C for 2
      d (15 degrees C->6 degrees C) showed that long-term cold acclimation extended the
      lethal time for 50% of the population (Lt(50)) during exposure to constant 0
      degrees C as much as 630-fold (from 0.137 h to 86.658 h). Such marked
      physiological plasticity in Lt(50) (in contrast to LLT) suggested that chronic
      indirect chilling injury at 0 degrees C differs from that caused by cold shock.
      Long-term cold acclimation modified the metabolomic profiles of the larvae.
      Accumulations of proline (up to 17.7 mM) and trehalose (up to 36.5 mM) were the
      two most prominent responses. In addition, restructuring of the
      glycerophospholipid composition of biological membranes was observed. The
      relative proportion of glycerophosphoethanolamines (especially those with
      linoleic acid at the sn-2 position) increased at the expense of
      glycerophosphocholines. CONCLUSION: Third-instar larvae of D. melanogaster
      improved their cold tolerance in response to long-term cold acclimation and
      showed metabolic potential for the accumulation of proline and trehalose and for
      membrane restructuring.

PMID- 21957474
TI  - Burrowing criteria and burrowing mode adjustment in bivalves to varying
      geoenvironmental conditions in intertidal flats and beaches.
AB  - The response of bivalves to their abiotic environment has been widely studied in
      relation to hydroenvironmental conditions, sediment types and sediment grain
      sizes. However, the possible role of varying geoenvironmental conditions in their
      habitats remains poorly understood. Here, we show that the hardness of the
      surficial intertidal sediments varies by a factor of 20-50 due to suction
      development and suction-induced void state changes in the essentially saturated
      states of intertidal flats and beaches. We investigated the response of two
      species of bivalves, Ruditapes philippinarum and Donax semigranosus, in the
      laboratory by simulating such prevailing geoenvironmental conditions in the
      field. The experimental results demonstrate that the bivalve responses depended
      strongly on the varying geoenvironmental conditions. Notably, both bivalves
      consistently shifted their burrowing modes, reducing the burrowing angle and
      burial depth, in response to increasing hardness, to compensate for the excessive
      energy required for burrowing, as explained by a proposed conceptual model. This
      burrowing mode adjustment was accompanied by two burrowing criteria below or
      above which the bivalves accomplished vertical burrowing or failed to burrow,
      respectively. The suitable and fatal conditions differed markedly with species
      and shell lengths. The acute sensitivities of the observed bivalve responses to
      geoenvironmental changes revealed two distinctive mechanisms accounting for the
      adult-juvenile spatial distributions of Ruditapes philippinarum and the
      behavioral adaptation to a rapidly changing geoenvironment of Donax semigranosus.
      The present results may provide a rational basis by which to understand the
      ensuing, and to predict future, bivalve responses to geoenvironmental changes in
      intertidal zones.

PMID- 21957473
TI  - A study of the evolution of human microRNAs by their apparent repression
      effectiveness on target genes.
AB  - BACKGROUND: Even though the genomes of many model species have already been
      sequenced, our knowledge of gene regulation in evolution is still very limited.
      One big obstacle is that it is hard to predict the target genes of
      transcriptional factors accurately from sequences. In this respect, microRNAs
      (miRNAs) are different from transcriptional factors, as target genes of miRNAs
      can be readily predicted from sequences. This feature of miRNAs offers an
      unprecedented vantage point for evolutionary analysis of gene regulation.
      METHODOLOGY/PRINCIPAL FINDINGS: In this study, we analyzed a particular aspect of
      miRNA evolution, the differences in the "apparent repression effectiveness (ARE)"
      between human miRNAs of different conservational levels. ARE is a measure we
      designed to evaluate the repression effect of miRNAs on target genes based on
      publicly available gene expression data in normal tissues and miRNA targeting and
      expression data. We found that ARE values of more conserved miRNAs are
      significantly higher than those of less conserved miRNAs in general. We also
      found the gain in expression abundance and broadness of miRNAs in evolution
      contributed to the gain in ARE. CONCLUSIONS/SIGNIFICANCE: The ARE measure
      quantifies the repressive effects of miRNAs and enables us to study the
      influences of many factors on miRNA-mediated repression, such as conservational
      levels and expression levels of miRNAs. The gain in ARE can be explained by the
      existence of a trend of miRNAs in evolution to effectively control more target
      genes, which is beneficial to the miRNAs but not necessarily to the organism at
      all times. Our results from miRNAs gave us an insight of the complex interplay
      between regulators and target genes in evolution.

PMID- 21957475
TI  - A functional nuclear localization sequence in the C. elegans TRPV channel OCR-2.
AB  - The ability to modulate gene expression in response to sensory experience is
      critical to the normal development and function of the nervous system. Calcium is
      a key activator of the signal transduction cascades that mediate the process of
      translating a cellular stimulus into transcriptional changes. With the recent
      discovery that the mammalian Ca(v)1.2 calcium channel can be cleaved, enter the
      nucleus and act as a transcription factor to control neuronal gene expression, a
      more direct role for the calcium channels themselves in regulating transcription
      has begun to be appreciated. Here we report the identification of a nuclear
      localization sequence (NLS) in the C. elegans transient receptor potential
      vanilloid (TRPV) cation channel OCR-2. TRPV channels have previously been
      implicated in transcriptional regulation of neuronal genes in the nematode,
      although the precise mechanism remains unclear. We show that the NLS in OCR-2 is
      functional, being able to direct nuclear accumulation of a synthetic cargo
      protein as well as the carboxy-terminal cytosolic tail of OCR-2 where it is
      endogenously found. Furthermore, we discovered that a carboxy-terminal portion of
      the full-length channel can localize to the nucleus of neuronal cells. These
      results suggest that the OCR-2 TRPV cation channel may have a direct nuclear
      function in neuronal cells that was not previously appreciated.

PMID- 21957476
TI  - Whatever the weather: ambient temperature does not influence the proportion of
      males born in New Zealand.
AB  - BACKGROUND: The proportion of male births has been shown to be over 50% in
      temperate climates around the world. Given that fluctuations in ambient
      temperature have previously been shown to affect sex allocation in humans, we
      examined the hypothesis that ambient temperature predicts fluctuations in the
      proportion of male births in New Zealand. METHODOLOGY/PRINCIPAL FINDINGS: We
      tested three main hypotheses using time series analyses. Firstly, we used
      historical annual data in New Zealand spanning 1876-2009 to test for a positive
      effect of ambient temperature on the proportion of male births. The proportion of
      males born ranged by 3.17%, from 0.504 to 0.520, but no significant relationship
      was observed between male birth rates and mean annual temperature in the
      concurrent or previous years. Secondly, we examined whether changes in annual
      ambient temperature were negatively related to the proportion of male stillbirths
      from 1929-2009 and whether the proportion of male stillbirths negatively affected
      the proportion of male live births. We found no evidence that fewer male
      stillbirths occurred during warmer concurrent or previous years, though a
      declining trend in the proportion of male stillbirths was observed throughout the
      data. Thirdly, we tested whether seasonal ambient temperatures, or deviations
      from those seasonal patterns, were positively related to the proportion of male
      births using monthly data from 1980-2009. Patterns of male and female births are
      seasonal, but very similar throughout the year, resulting in a non-seasonal
      proportion of male births. However, no cross correlations between proportion of
      male births and lags of temperature were significant. CONCLUSIONS: Results
      showed, across all hypotheses under examination, that ambient temperatures were
      not related to the proportion of male births or the proportion of male
      stillbirths in New Zealand. While there is evidence that temperature may
      influence human sex allocation elsewhere, such effects of temperature are not
      universal.

PMID- 21957478
TI  - Suppression of cellular transformation by poly (A) binding protein interacting
      protein 2 (Paip2).
AB  - Controlling translation is crucial for the homeostasis of a cell. Its
      deregulation can facilitate the development and progression of many diseases
      including cancer. Poly (A) binding protein interacting protein 2 (Paip2) inhibits
      efficient initiation of translation by impairing formation of the necessary
      closed loop of mRNA. The over production of Paip2 in the presence of a
      constitutively active form of hRas(V12) can reduce colony formation in a semi
      solid matrix and focus formation on a cell monolayer. The ability of Paip2 to
      bind to Pabp is required to suppress the transformed phenotype mediated by
      hRas(V12). These observations indicate that Paip2 is able to function as a tumor
      suppressor.

PMID- 21957477
TI  - Is there a classical nonsense-mediated decay pathway in trypanosomes?
AB  - In many eukaryotes, messenger RNAs with premature termination codons are
      destroyed by a process called "nonsense-mediated decay", which requires the RNA
      helicase Upf1 and also, usually, an interacting factor, Upf2. Recognition of
      premature termination codons may rely on their distance from either a splice site
      or the polyadenylation site, and long 3'-untranslated regions can trigger mRNA
      decay. The protist Trypanosoma brucei relies heavily on mRNA degradation to
      determine mRNA levels, and 3'-untranslated regions play a major role in control
      of mRNA decay. We show here that trypanosomes have a homologue of Upf1, TbUPF1,
      which interacts with TbUPF2 and (in an RNA-dependent fashion) with poly(A)
      binding protein 1, PABP1. Introduction of a premature termination codon in either
      an endogenous gene or a reporter gene decreased mRNA abundance, as expected for
      nonsense-mediated decay, but a dependence of this effect on TbUPF1 could not be
      demonstrated, and depletion of TbUPF1 by over 95% had no effect on parasite
      growth or the mRNA transcriptome. Further investigations of the reporter mRNA
      revealed that increases in open reading frame length tended to increase mRNA
      abundance. In contrast, inhibition of translation, either using 5'-secondary
      structures or by lengthening the 5'-untranslated region, usually decreased
      reporter mRNA abundance. Meanwhile, changing the length of the 3'-untranslated
      region had no consistent effect on mRNA abundance. We suggest that in
      trypanosomes, translation per se may inhibit mRNA decay, and interactions with
      multiple RNA-binding proteins preclude degradation based on 3'-untranslated
      region length alone.

PMID- 21957479
TI  - Follow my eyes: the gaze of politicians reflexively captures the gaze of ingroup
      voters.
AB  - Studies in human and non-human primates indicate that basic socio-cognitive
      operations are inherently linked to the power of gaze in capturing reflexively
      the attention of an observer. Although monkey studies indicate that the automatic
      tendency to follow the gaze of a conspecific is modulated by the leader-follower
      social status, evidence for such effects in humans is meager. Here, we used a
      gaze following paradigm where the directional gaze of right- or left-wing Italian
      political characters could influence the oculomotor behavior of ingroup or
      outgroup voters. We show that the gaze of Berlusconi, the right-wing leader
      currently dominating the Italian political landscape, potentiates and inhibits
      gaze following behavior in ingroup and outgroup voters, respectively.
      Importantly, the higher the perceived similarity in personality traits between
      voters and Berlusconi, the stronger the gaze interference effect. Thus, higher
      order social variables such as political leadership and affiliation prepotently
      affect reflexive shifts of attention.

PMID- 21957480
TI  - An unprecedented role reversal: ground beetle larvae (Coleoptera: Carabidae) lure
      amphibians and prey upon them.
AB  - Amphibians often feed on beetle larvae, including those of ground beetles
      (Carabidae). Preliminary reports have detailed an unusual trophic interaction in
      which, in contrast, larvae of the ground beetle Epomis prey upon juvenile and
      adult amphibians. While it is known that these larvae feed exclusively on
      amphibians, how the predator-prey encounter occurs to the advantage of the beetle
      larvae had been unknown to date. Using laboratory observations and controlled
      experiments, we recorded the feeding behavior of Epomis larvae, as well as the
      behavior of their amphibian prey. Here we reveal that larvae of two species of
      Epomis (E. circumscriptus and E. dejeani) lure their potential predator, taking
      advantage of the amphibian's predation behavior. The Epomis larva combines a sit
      and-wait strategy with unique movements of its antennae and mandibles to draw the
      attention of the amphibian to the presence of a potential prey. The intensity of
      this enticement increases with decreasing distance between the larva and the
      amphibian. When the amphibian attacks, the larva almost always manages to avoid
      the predator's protracted tongue, exploiting the opportunity to attach itself to
      the amphibian's body and initiate feeding. Our findings suggest that the trophic
      interaction between Epomis larvae and amphibians is one of the only natural cases
      of obligatory predator-prey role reversal. Moreover, this interaction involves a
      small insect larva that successfully lures and preys on a larger vertebrate. Such
      role reversal is exceptional in the animal world, extending our perspective of co
      evolution in the arms race between predator and prey, and suggesting that
      counterattack defense behavior has evolved into predator-prey role reversal.

PMID- 21957481
TI  - Anticancer effects of 15d-prostaglandin-J2 in wild-type and doxorubicin-resistant
      ovarian cancer cells: novel actions on SIRT1 and HDAC.
AB  - 15-Deoxy-delta-12,14-prostaglandin-J(2) (15d-PGJ(2)), an arachidonic metabolite
      and a natural PPARgamma agonist, is known to induce apoptosis in tumor cells. In
      this study, we investigated new therapeutic potentials of 15d-PGJ(2) by
      determining its anticancer effects in wild-type and doxorubicin-resistant ovarian
      carcinoma cells. Despite high expression of resistance-inducing genes like MDR1,
      Bcl2 and Bcl-xl, 15d-PGJ(2) strongly induced apoptosis in doxorubicin-resistant
      (A2780/AD) cells similar to the wild-type (A2780). This was found to be related
      to caspase-3/7- and NF-kappaB pathways but not to its PPARgamma agonistic
      activity. 15d-PGJ(2) also was able to reduce the doxorubicin resistance of
      A2780/AD cells at low doses as confirmed by the inhibition of gene expression of
      MDR1 (p-glycoprotein) and SIRT1 (a drug senescence gene). We also investigated
      effects of 15d-PGJ(2) on cell migration and transformation using a wound-healing
      assay and morphological analyses, respectively. We found that 15d-PGJ(2)
      inhibited migration most likely due to NF-kappaB inhibition and induced
      transformation of the round-shape A2780/AD cells into elongated epithelial cells
      due to HDAC1 inhibition. Using a 15d-PGJ(2) analog, we found the mechanism of
      action of these new activities of 15d-PGJ(2) on SIRT1 and HDAC1 gene expressions
      and enzyme activities. In conclusion, the present study demonstrates that 15d
      PGJ(2) has a high therapeutic potential to kill drug-resistant tumor cells and,
      the newly described inhibitory effects of this cyclo-oxygenase product on SIRT1
      and HDAC will provide new opportunities for cancer therapeutics.

PMID- 21957482
TI  - Activated microglia inhibit axonal growth through RGMa.
AB  - By causing damage to neural networks, spinal cord injuries (SCI) often result in
      severe motor and sensory dysfunction. Functional recovery requires axonal
      regrowth and regeneration of neural network, processes that are quite limited in
      the adult central nervous system (CNS). Previous work has shown that SCI lesions
      contain an accumulation of activated microglia, which can have multiple
      pathophysiological influences. Here, we show that activated microglia inhibit
      axonal growth via repulsive guidance molecule a (RGMa). We found that microglia
      activated by lipopolysaccharide (LPS) inhibited neurite outgrowth and induced
      growth cone collapse of cortical neurons in vitro--a pattern that was only
      observed when there was direct contact between microglia and neurons. After
      microglia were activated by LPS, they increased expression of RGMa; however,
      treatment with RGMa-neutralizing antibodies or transfection of RGMa siRNA
      attenuated the inhibitory effects of microglia on axonal outgrowth. Furthermore,
      minocycline, an inhibitor of microglial activation, attenuated the effects of
      microglia and RGMa expression. Finally, we examined whether these in vitro
      patterns could also be observed in vivo. Indeed, in a mouse SCI model,
      minocycline treatment reduced the accumulation of microglia and decreased RGMa
      expression after SCI, leading to reduced dieback in injured corticospinal tracts.
      These results suggest that activated microglia play a major role in inhibiting
      axon regeneration via RGMa in the injured CNS.

PMID- 21957483
TI  - The Pbx interaction motif of Hoxa1 is essential for its oncogenic activity.
AB  - Hoxa1 belongs to the Hox family of homeodomain transcription factors involved in
      patterning embryonic territories and governing organogenetic processes. In
      addition to its developmental functions, Hoxa1 has been shown to be an oncogene
      and to be overexpressed in the mammary gland in response to a deregulation of the
      autocrine growth hormone. It has therefore been suggested that Hoxa1 plays a
      pivotal role in the process linking autocrine growth hormone misregulation and
      mammary carcinogenesis. Like most Hox proteins, Hoxa1 can interact with Pbx
      proteins. This interaction relies on a Hox hexapeptidic sequence centred on
      conserved Tryptophan and Methionine residues. To address the importance of the
      Hox-Pbx interaction for the oncogenic activity of Hoxa1, we characterized here
      the properties of a Hoxa1 variant with substituted residues in the hexapeptide
      and demonstrate that the Hoxa1 mutant lost its ability to stimulate cell
      proliferation, anchorage-independent cell growth, and loss of contact inhibition.
      Therefore, the hexapeptide motif of Hoxa1 is required to confer its oncogenic
      activity, supporting the view that this activity relies on the ability of Hoxa1
      to interact with Pbx.

PMID- 21957484
TI  - An important role for syndecan-1 in herpes simplex virus type-1 induced cell-to
      cell fusion and virus spread.
AB  - Herpes simplex virus type-1 (HSV-1) is a common human pathogen that relies
      heavily on cell-to-cell spread for establishing a lifelong latent infection.
      Molecular aspects of HSV-1 entry into host cells have been well studied; however,
      the molecular details of the spread of the virus from cell-to-cell remain poorly
      understood. In the past, the role of heparan sulfate proteoglycans (HSPG) during
      HSV-1 infection has focused solely on the role of HS chains as an attachment
      receptor for the virus, while the core protein has been assumed to perform a
      passive role of only carrying the HS chains. Likewise, very little is known about
      the involvement of any specific HSPGs in HSV-1 lifecycle. Here we demonstrate
      that a HSPG, syndecan-1, plays an important role in HSV-1 induced membrane fusion
      and cell-to-cell spread. Interestingly, the functions of syndecan-1 in fusion and
      spread are independent of the presence of HS on the core protein. Using a mutant
      CHO-K1 cell line that lacks all glycosaminoglycans (GAGs) on its surface (CHO
      745) we demonstrate that the core protein of syndecan-1 possesses the ability to
      modulate membrane fusion and viral spread. Altogether, we identify a new role for
      syndecan-1 in HSV-1 pathogenesis and demonstrate HS-independent functions of its
      core protein in viral spread.

PMID- 21957485
TI  - Completeness and changes in registered data and reporting bias of randomized
      controlled trials in ICMJE journals after trial registration policy.
AB  - OBJECTIVE: We assessed the adequacy of randomized controlled trial (RCT)
      registration, changes to registration data and reporting completeness for
      articles in ICMJE journals during 2.5 years after registration requirement
      policy. METHODS: For a set of 149 reports of 152 RCTs with ClinicalTrials.gov
      registration number, published from September 2005 to April 2008, we evaluated
      the completeness of 9 items from WHO 20-item Minimum Data Set relevant for
      assessing trial quality. We also assessed changes to the registration elements at
      the Archive site of ClinicalTrials.gov and compared published and registry data.
      RESULTS: RCTs were mostly registered before 13 September 2005 deadline (n = 101,
      66.4%); 118 (77.6%) started recruitment before and 31 (20.4%) after registration.
      At the time of registration, 152 RCTs had a total of 224 missing registry fields,
      most commonly 'Key secondary outcomes' (44.1% RCTs) and 'Primary outcome'
      (38.8%). More RCTs with post-registration recruitment had missing Minimum Data
      Set items than RCTs with pre-registration recruitment: 57/118 (48.3%) vs. 24/31
      (77.4%) (chi(2) (1) = 7.255, P = 0.007). Major changes in the data entries were
      found for 31 (25.2%) RCTs. The number of RCTs with differences between registered
      and published data ranged from 21 (13.8%) for Study type to 118 (77.6%) for
      Target sample size. CONCLUSIONS: ICMJE journals published RCTs with proper
      registration but the registration data were often not adequate, underwent
      substantial changes in the registry over time and differed in registered and
      published data. Editors need to establish quality control procedures in the
      journals so that they continue to contribute to the increased transparency of
      clinical trials.

PMID- 21957486
TI  - GLP-1 analogs reduce hepatocyte steatosis and improve survival by enhancing the
      unfolded protein response and promoting macroautophagy.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a known outcome of
      hepatosteatosis. Free fatty acids (FFA) induce the unfolded protein response
      (UPR) or endoplasmic reticulum (ER) stress that may induce apoptosis. Recent data
      indicate ER stress to be a major player in the progression of fatty liver to more
      aggressive lesions. Autophagy on the other hand has been demonstrated to be
      protective against ER stress-induced cell death. We hypothesized that exendin-4
      (GLP-1 analog) treatment of fat loaded hepatocytes can reduce steatosis by
      autophagy which leads to reduced ER stress-related hepatocyte apoptosis.
      METHODOLOGY/PRINCIPAL FINDINGS: Primary human hepatocytes were loaded with
      saturated, cis- and trans-unsaturated fatty acids (palmitic, oleic and elaidic
      acid respectively). Steatosis, induced with all three fatty acids, was
      significantly resolved after exendin-4 treatment. Exendin-4 sustained levels of
      GRP78 expression in fat-loaded cells when compared to untreated fat-loaded cells
      alone. In contrast, CHOP (C/EBP homologous protein); the penultimate protein that
      leads to ER stress-related cell death was significantly decreased by exendin-4 in
      hepatocytes loaded with fatty acids. Finally, exendin-4 in fat loaded hepatocytes
      clearly promoted gene products associated with macroautophagy as measured by
      enhanced production of both Beclin-1 and LC3B-II, markers for autophagy; and
      visualized by transmission electron microscopy (TEM). Similar observations were
      made in mouse liver lysates after mice were fed with high fat high fructose diet
      and treated with a long acting GLP-1 receptor agonist, liraglutide.
      CONCLUSIONS/SIGNIFICANCE: GLP-1 proteins appear to protect hepatocytes from fatty
      acid-related death by prohibition of a dysfunctional ER stress response; and
      reduce fatty acid accumulation, by activation of both macro-and chaperone
      mediated autophagy. These findings provide a novel role for GLP-1 proteins in
      halting the progression of more aggressive lesions from underlying steatosis in
      humans afflicted with NAFLD.

PMID- 21957488
TI  - Electrochemical evidences and consequences of significant differences in ions
      diffusion rate in polyacrylate-based ion-selective membranes.
AB  - The origin and effect of surface accumulation of primary ions within the ion
      selective poly(n-butyl acrylate)-based membrane, obtained by thermal
      polymerization, is discussed. Using a new method, based on the relation between
      the shape of a potentiometric plot and preconditioning time, the diffusion of
      copper ions in the membrane was found to be slow (the diffusion coefficient
      estimated to be close to 10(-11) cm(2) s(-1)), especially when compared to ion
      exchanger counter ions--sodium cations diffusion (a diffusion coefficient above
      10(-9) cm(2) s(-1)). The higher mobility of sodium ions than those of the copper
      ionophore complex results in exposed ion-exchanger role leading to undesirably
      exposed sensitivity to sodium or potassium ions.

PMID- 21957487
TI  - Hepcidin is involved in iron regulation in the ischemic brain.
AB  - Oxidative stress plays an important role in neuronal injuries caused by cerebral
      ischemia. It is well established that free iron increases significantly during
      ischemia and is responsible for oxidative damage in the brain. However, the
      mechanism of this ischemia-induced increase in iron is not completely understood.
      In this report, the middle cerebral artery occlusion (MCAO) rat model was
      performed and the mechanism of iron accumulation in cerebral ischemia-reperfusion
      was studied. The expression of L-ferritin was significantly increased in the
      cerebral cortex, hippocampus, and striatum on the ischemic side, whereas H
      ferritin was reduced in the striatum and increased in the cerebral cortex and
      hippocampus. The expression level of the iron-export protein ferroportin1 (FPN1)
      significantly decreased, while the expression of transferrin receptor 1 (TfR1)
      was increased. In order to elucidate the mechanisms of FPN1 regulation, we
      studied the expression of the key regulator of FPN1, hepcidin. We observed that
      the hepcidin level was significantly elevated in the ischemic side of the brain.
      Knockdown hepcidin repressed the increasing of L-ferritin and decreasing of FPN1
      invoked by ischemia-reperfusion. The results indicate that hepcidin is an
      important contributor to iron overload in cerebral ischemia. Furthermore, our
      results demonstrated that the levels of hypoxia-inducible factor-1alpha (HIF
      1alpha) were significantly higher in the cerebral cortex, hippocampus and
      striatum on the ischemic side; therefore, the HIF-1alpha-mediated TfR1 expression
      may be another contributor to the iron overload in the ischemia-reperfusion
      brain.

PMID- 21957489
TI  - Oxidation of Akt2 kinase promotes cell migration and regulates G1-S transition in
      the cell cycle.
AB  - Phosphorylation has long been recognized as the key mediator of protein
      signaling. New modes of signaling regulation are emerging with the development of
      specific chemical probes and application of high-throughput mass spectrometry
      technologies. Using biotin-tagged chemical probes for protein oxidation, mass
      spectrometry and functional assays, our group has recently reported isoform
      specific oxidation of Akt2 in response to PDGF signaling. The studies included
      here investigate the functional consequence of oxidation on Akt2-mediated cell
      migration and cell cycle. Akt2-KO MEFs transduced with WT and Cys124Ser Akt2 were
      used as the model system for these studies. The implications of these findings on
      disease pathology are discussed.

PMID- 21957491
TI  - Cyclooxygenase (COX)-1 takes control of adult hippocampal neurogenesis.

PMID- 21957490
TI  - The ups and downs of p53 regulation in hematopoietic stem cells.
AB  - Hematopoietic stem cells provide an indispensible source for replenishing the
      blood with all its constituents throughout the organism's lifetime. Mice with a
      compromised hematopoietic stem cell compartment cannot survive. p53, a major
      tumor suppressor gene, has been implicated in regulation of hematopoiesis. In
      particular, p53 plays a role in homeostasis by regulating HSC quiescence and self
      renewal. We recently utilized a hypomorphic p53(515C) allele in conjunction with
      Mdm2, a negative regulator of p53 to gain insights into the role of p53 in
      hematopoietic regulation. Our analyses revealed that p53(515C/515C) Mdm2(-/-)
      double mutant mice die soon after birth due to hematopoietic failure. Further
      mechanistic studies revealed that in the absence of Mdm2, ROS induced postnatal
      p53 activity depletes hematopoietic stem cells, progenitors and differentiated
      cells.

PMID- 21957492
TI  - Role of caspase 9 in activation of HTLV-1 LTR expression by DNA damaging agents.
AB  - Adult T-cell leukemia (ATL) is caused by HTLV-I. The viral Tax oncoprotein plays
      a central role in initiating the process to ATL. However, after infection HTLV-1
      enters into latency, during which virus gene expression is very low, so that the
      level of Tax is likely insufficient for exerting its oncogenic activities.
      Therefore only 5% of the infected individuals may develop ATL several decades
      after infection. It is assumed that the transition from latency to ATL
      development requires at least a temporary activation of the latent virus in order
      to elevate Tax to its oncogenic threshold. We have previously found that DNA
      damaging agents, which usually induce apoptosis, can also activate the viral LTR
      and that the anti apoptosis Bcl-2 protein not only avoid their apoptosis
      induction but concomitantly prevents their LTR activation effect. Therefore, the
      present study was designed to identify the factor that while participating in the
      apoptotic cascade acts also to activate the viral LTR. For this purpose we
      employed ectopic vectors expressing these apoptotic factors together with potent
      shRNAs against each of them and anti caspase peptide inhibitors. We have found
      that in addition to its function as initiator of the mitochondrial apoptotic
      cascade, caspase 9 can acts also as an executer which among other non-apoptotic
      functions it forms an Sp1-p53 complex that activates the LTR by binding to an Sp1
      recognition site residing in the LTR. This finding can help in designing
      effective preventing strategies against ATL development in clinically latent HTLV
      1 carriers.

PMID- 21957493
TI  - The stem cell patent landscape as relevant to cancer vaccines.
AB  - Cancer vaccine targeting cancer stem cells is proposed to serve as a potent
      immunotherapy. Thus, it would be useful to examine the main trends in stem cell
      patenting activity as a guide for those seeking to develop such cancer vaccines.
      We found that a substantial number of stem cell patents were granted up to the
      end of 2010, including ~2000 issued in the US. Many of these have been filed
      since 2001, including 7,551 applications in the US. Stem cell development, as
      evidenced by the numbers of PubMed articles, has matured steadily in recent
      years. However, the other metrics, such as the number of patent applications, the
      technology-science linkage and the number of patent assignees, have been
      stagnant. Moreover, the ownership of stem cell patents is still quiet fragmented
      across multiple organizations, and the number of stem cell patent assignees from
      the business sector has not increased significantly. Academic and nonprofit
      institutions not only account for a large share of stem cell patents but also
      apply for patents continually. Based on this analysis, the strength of stem cell
      resources seems to remain stagnant in recent years due to the ban on government
      funding of embryonic stem cell research. Furthermore, the patent prosecution or
      technical barriers in the field of stem cells would be another main reason that
      the number of US-issued stem cell patents for each application have been in
      gradual decline since 2000. Therefore, we consider stem cell technology to still
      be under development.

PMID- 21957494
TI  - Two doses of pandemic influenza A(H1N1) vaccine: tolerability in healthy young
      children in the Netherlands.
AB  - During the 2009 influenza pandemic, children aged 6 months up to and including 4
      years, without chronic illness, were vaccinated with two doses of Pandemrix((r))
      through mass vaccination in the Netherlands. During the vaccination campaign a
      warning was issued about fever after the second dose of Pandemrix((r)).
      Therefore, we investigated the tolerability of both doses Pandemrix((r)) in these
      children. Among parents of children eligible for vaccination, 1500 questionnaires
      were distributed during both, the first and second mass vaccination session. We
      asked for the occurrence, time interval, and duration of local reactions and
      systemic adverse events (AEs). The responses were 36.7% and 29.5% after each
      dose, respectively. Local reactions were reported in 40.4% and 39.3%, most
      frequently, pain at the injection site. After the first and second dose, 29.6%
      and 30.7% of all children experienced fever (mean temperature 38.8{degree
      sign}C). Other systemic AEs were reported in 41.6% and 42.9% of the children. No
      differences were seen between the first and second dose for all reported AEs
      except for pallor. One child was hospitalized after the first dose, but a causal
      relation to the vaccination was considered improbable. In conclusion, fever was
      frequently reported in children 6 months up to and including 4 years of age after
      the first and second dose of Pandemrix((r)). However, for almost all AEs,
      including fever, no dose effect was observed. Reported AEs were mostly mild and
      all were transient.

PMID- 21957495
TI  - 7SK snRNA-mediated, gene-specific cooperativity of HMGA1 and P-TEFb.
AB  - 7SK small-nuclear RNA has been shown to negatively regulate P-TEFb transcription
      elongation on the one hand and control HMGA1 transcription initiation and
      chromatin remodeling on the other. The non-coding 7SK RNA thereby directly
      interacts with both factors through different regions. While the loop 2 of the
      RNA specifically binds to the first HMGA1 A/T hook, thereby competing with DNA
      binding to the same domain, loops 1, 3 and 4 are involved in P-TEFb interaction.
      This raises the question of whether HMGA1 and P-TEFb cooperate during gene
      transcription. Using transcriptome profiling, we have identifed genes that are
      oppositely regulated by 7SK RNA over-expression versus shRNA mediated knock-down.
      Inhibition of P-TEFb by competitive expression of a dominant-negative Cdk9
      protein leads to highly similar changes in global gene expression as the over
      expression of 7SK RNA, confirming the importance of P-TEFb inhibition by 7SK RNA.
      Furthermore, we have similarly assembled genes affected concomitantly by HMGA1
      over-expression. HMGA1 and P-TEFb, in the case of select target genes, show
      strong cooperation in transcriptional activation. Finally, we provide evidence
      for 7SK RNA complexes containing simultaneously HMGA1 and P-TEFb. 7SK RNA thus
      establishes gene-dependent plasticity between HMGA1 chromatin remodeling and
      transcription initiation and P-TEFb transcription elongation.

PMID- 21957496
TI  - Differential effects of PKA-controlled CaMKK2 variants on neuronal
      differentiation.
AB  - Regulation between protein kinases is critical for the establishment of signaling
      pathways/networks to 'orchestrate' cellular processes. Besides posttranslational
      phosphorylation, alternative pre-mRNA splicing is another way to control kinase
      properties, but splicing regulation between two kinases and the effect of
      resulting variants on cells has barely been explored. Here we examined the effect
      of the protein kinase A (PKA) pathway on the alternative splicing and variant
      properties of the Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2) gene
      in B35 neuroblastoma cells. Inclusion of the exon 16 of CaMKK2 was significantly
      reduced by H89, a PKA selective inhibitor. Consistently, overexpressed PKA
      strongly promoted the exon inclusion in a CaMKK2 sequence-dependent way in
      splicing reporter assays. In vitro, purified CaMKKbeta1 variant proteins were
      found to be kinase-active. In cells, they were differentially phosphorylated by
      PKA. In RNA interference assays, CaMKKbeta1 was found to be essential for
      forskolin-induced neurite growth. Interestingly, overexpression of the variant
      without exon 16 (-E16) promoted neurite elongation while the other one (+E16)
      promoted neurite branching; in contrast, reduction of the latter one enhanced
      neurite elongation. Moreover, the variants are differentially expressed and the
      exon 16-containing transcripts highly enriched in the brain, particularly the
      cerebellum and hippocampus. Thus, PKA regulates the alternative splicing of
      CaMKK2 to produce variants that differentially modulate neuronal differentiation.
      Taken together with the many distinct variants of kinases, alternative splicing
      regulation likely adds another layer of modulation between protein kinases in
      cellular signaling networks.

PMID- 21957498
TI  - Illumination of Arabidopsis roots induces immediate burst of ROS production.
AB  - Arabidopsis roots are routinely exposed to light both during their cultivation
      within transparent Petri dishes and during their confocal microscopy analysis.
      Here we report that illumination of roots which naturally grow in darkness, even
      for a few seconds, induces an immediate and strong burst of reactive oxygen
      species (ROS). Plant scientists studying roots should pay great attention to the
      environment of living roots, and keep them in darkness as long as possible.
      Results obtained using illuminated roots during in vivo microscopic analysis
      should also be interpreted with great caution.

PMID- 21957497
TI  - Quantitative mass spectrometry of DENV-2 RNA-interacting proteins reveals that
      the DEAD-box RNA helicase DDX6 binds the DB1 and DB2 3' UTR structures.
AB  - Dengue virus (DENV) is a rapidly re-emerging flavivirus that causes dengue fever
      (DF), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), diseases
      for which there are no available therapies or vaccines.  The DENV-2 positive
      strand RNA genome contains 5' and 3' untranslated regions (UTRs) that have been
      shown to form secondary structures required for virus replication and interaction
      with host cell proteins.  In order to comprehensively identify host cell factors
      that bind the DENV-2 UTRs, we performed RNA chromatography, using the DENV-2 5'
      and 3' UTRs as "bait", combined with quantitative mass spectrometry.  We
      identified several proteins, including DDX6, G3BP1, G3BP2, Caprin1, and USP10,
      implicated in P body (PB) and stress granule (SG) function, and not previously
      known to bind DENV RNAs.  Indirect immunofluorescence microscopy showed these
      proteins to colocalize with the DENV replication complex.  Moreover, DDX6
      knockdown resulted in reduced amounts of infectious particles and viral RNA in
      tissue culture supernatants following DENV infection. DDX6 interacted with DENV
      RNA in vivo during infection and in vitro this interaction was mediated by the
      DB1 and DB2 structures in the 3' UTR, possibly by formation of a pseudoknot
      structure.  Additional experiments demonstrate that, in contrast to DDX6, the SG
      proteins G3BP1, G3BP2, Caprin1 and USP10 bind to the variable region (VR) in the
      3' UTR.  These results suggest that the DENV-2 3' UTR is a site for assembly of
      PB and SG proteins and, for DDX6, assembly on the 3' UTR is required for DENV
      replication.

PMID- 21957499
TI  - Distribution pattern of small RNA and degradome reads provides information on
      miRNA gene structure and regulation.
AB  - Plant microRNAs (miRNAs) have an impact in the regulation of several biological
      processes such as development, growth and metabolism by negatively controlling
      gene expression at the post-transcriptional level. However, the role of these
      small molecules in the symbiotic interaction of plant roots and arbuscular
      mycorrhizal (AM) fungi remained elusive. To elucidate the role of miRNAs during
      AM symbiosis we used a deep sequencing approach to analyze the small RNA and
      degradome sequence tags of Medicago truncatula non-mycorrhizal and mycorrhizal
      roots. We identified 243 novel Medicago microRNAs and 118 mRNA cleavage targets
      of miRNA mature and star sequences. Several AM symbiosis-relevant genes were
      identified as miRNA targets. The transcript of MtNsp2, encoding a GRAS
      transcription factor involved in the nodule and mycorrhizal signaling pathway, is
      cleaved by a novel member of the miR171 gene family, namely miR171h. Here, we
      carried out a detailed analysis of the genomic structure of the MIR171h gene
      comprising our deep sequencing data. The results suggest a feedback circuit
      between mature miR171h and its own primary transcript showing the ability of this
      miRNA regulating itself.

PMID- 21957500
TI  - Endoscopy and surgery: a matter of diagnostic enlightenment & therapeutic
      liberty.

PMID- 21957501
TI  - [Societal factors determining health (13). Malnutrition of the aged and their
      socioeconomic status].

PMID- 21957502
TI  - [Health service Research (10). Primary care and health service research: from a
      viewpoint to nurture a research mind in medical education].

PMID- 21957503
TI  - [Public health in scientific analysis of society and health (6). Policies related
      to regional health care and hospitals based on data (1)].

PMID- 21957504
TI  - [Development of depressive symptoms in middle-aged and aged populations and its
      relationship with stresses in their daily lives--a cross-sectional study of a
      large population group representing general population in Japan].

PMID- 21957505
TI  - [The relationship between child and adolescent psychiatry and traditional
      psychiatry--with reference to several diseases].

PMID- 21957506
TI  - [The relationship between pediatric and adult psychiatry in relation to
      developmental disorders].

PMID- 21957507
TI  - Modeling patient flow operation of a US urban county hospital.
AB  - System dynamics modeling methodology is well suited to address the constantly
      changing complexity that characterizes designing a modern urban hospital's
      patient flow operation. It involves the development of simulation models that
      portray process flows and feedback that may be tested to find effective designs
      to overcome ineffective means of healthcare delivery. An urban county hospital
      (UCH) in Minnesota, USA is used to demonstrate a modular system dynamics modeling
      approach to simulate and optimize internal patient and process flow where major
      costs are also considered. This allows decision makers to visualize overall
      efficiencies through optimal bed capacity for peak patient flow of emergency and
      routine patients in a large healthcare delivery operation.

PMID- 21957508
TI  - Semantic component of a cross-modal Stroop-like task.
AB  - Three experiments showed that the pattern of interference of single-modality
      Stroop tests also exists cross-modally. Distractors and targets were either
      pictures or auditory words. In a naming task (Experiment 1), word distractors
      from the same semantic category as picture targets interfered with picture naming
      more than did semantically unrelated distractors; the semantic category of
      picture distractors did not differentially affect word naming. In a
      categorization task (Experiment 2), this Stroop-like effect was reversed: Picture
      distractors from the same semantic category as word targets interfered less with
      word categorization than picture distractors that were semantically unrelated;
      the semantic category of word distractors did not differentially affect picture
      categorization. Experiment 3 replicated these effects when each subject performed
      both tasks; the task, naming or categorizing, determined the pattern of
      interference between pictures and auditory words. The results thus support the
      existence of a semantic component of a cross-modal Stroop-like effect.

PMID- 21957509
TI  - [Emotions motivate action and communication].

PMID- 21957510
TI  - Validation of a CT image based software for three-dimensional measurement of
      acetabular cup orientation.
AB  - The purpose of our study was to develop a simple and reproducible method for
      calculating post-operative acetabular cup position based upon computed
      tomographic images. Next, we sought to examine the reliability, objectivity and
      accuracy of this method. We developed a 3D CT evaluation software based upon
      Amira(r) (data visualisation, analysis and modelling software) to calculate the
      abduction and anteversion of the acetabular cup relative to the APP (anterior
      pelvic plane). To test the accuracy of the method, we constructed a special
      phantom pelvic model as the gold standard, in which the acetabulum was mounted at
      various abduction and anteversion angles that had previously been measured
      digitally. This phantom was then CT scanned in 12 different cup positions (30
      degrees  to 50 degrees  abduction, 0 degrees  to 30 degrees  anteversion) and
      then evaluated using the 3D CT evaluation software. In addition, we also examined
      the reliability and objectivity of this method in 10 patients following
      implantation of a hip prosthesis, as a clinical trial. We observed an average
      accuracy of the 3D CT evaluation software of -0.3 degrees  (range -1.4 degrees 
      to 1.3 degrees ; SD 0.6 degrees ) for abduction and 0.2 degrees  (range -1.4
      degrees  to 1.4 degrees ; SD 0.6 degrees ) for anteversion compared with the gold
      standard. Moreover, a high intra -and interindividual agreement in the resulting
      ICC well above 0.8 for abduction and abduction values in the phantom study and
      the clinical trial were observed. This study found that the 3D CT evaluation
      software provides high reliability, objectivity and accuracy. Thus, the 3D CT
      software is a method that permits very precise evaluation of the post-operative
      cup position independent of patient positioning or pelvic tilt.

PMID- 21957511
TI  - Technology growth and expenditure growth in health care.

PMID- 21957512
TI  - Demand for health insurance among the uninsured.

PMID- 21957513
TI  - "Whistleblowers will face bullying from every side".

PMID- 21957514
TI  - Nurses hit by pension hike.

PMID- 21957516
TI  - "Put down the pitchfork--the workers are getting it right".

PMID- 21957515
TI  - "A defining feature of Scotland's health system is partnership".

PMID- 21957517
TI  - "Respiratory strategy must be acted on if care is to improve".

PMID- 21957518
TI  - Assessing the value of specialist nurses.
AB  - Despite an enormous growth in specialist nurse-led activity, specialist nursing
      posts are under threat. This article discusses why clinical specialist nursing
      roles are at risk. It also looks at what specialist nurses can do to prove their
      value and help protect their positions.

PMID- 21957519
TI  - Productivity gains by specialist nurses.
AB  - Workload analysis showed that the specialist nursing service in lung cancer in an
      acute hospital was being used primarily to support processes and administration
      rather than providing holistic cancer care. An analysis of the inpatient
      population showed that many people were being admitted for non-acute problems,
      such as symptom control in advanced disease. As the key workers for patients with
      lung cancer, the clinical nurse specialists negotiated away the administrative
      burden and adopted standard, proactive case management in line with national
      standards. Their proactive and vigilant case management resulted in a drop in
      admissions for non-acute problems from four to a mean of 0.3 per month. This
      represents a significant saving in bed days. Clinical nurse specialists who
      practise proactive case management and re-focus services in line with best
      practice represent a good return on investment.

PMID- 21957520
TI  - Reflections by clinical nurse specialists on changing ward practice.
AB  - In September 2010, palliative care clinical nurse specialists at North Middlesex
      University Hospital Trust introduced competencies for all nurses in setting up
      and using syringe drivers. This was done after the trust identified a high level
      of clinical incidents involving syringe drivers. This article discusses how the
      competencies were implemented and assessed, explores the importance of
      understanding change management to achieve change, and how different leadership
      styles affect changes to practice.

PMID- 21957521
TI  - Ischaemic heart disease prevention.

PMID- 21957522
TI  - Hypertonic saline for bronchiectasis.
AB  - Despite intervention, some patients with bronchiectasis struggle to clear
      secretions. An advanced practitioner in respiratory medicine at Salford Royal
      Foundation Trust identified nebulised hypertonic saline (HTS) as a treatment that
      could potentially improve service provision. She developed and evaluated a safe
      drug challenge and monitoring service for nebulised HTS.

PMID- 21957523
TI  - Why do I have to apply for ethical approval before I can begin my research?

PMID- 21957524
TI  - Rising mist.

PMID- 21957525
TI  - Leading by example: the physician's role in quality improvement.

PMID- 21957526
TI  - New "I'm sorry" law does not immunize physicians from admitted malpractice.

PMID- 21957528
TI  - Self-reliance, self-sufficient, sustainability.

PMID- 21957527
TI  - MSMS - Physicians Insurance Agency.

PMID- 21957529
TI  - The impact of tax reform on Michigan physicians.

PMID- 21957530
TI  - The doctors company protects Michigan members from fastest growing practice
      threat with CyberGuard.

PMID- 21957531
TI  - Understanding the Medicaid EHR Incentive Program.

PMID- 21957532
TI  - Why is this patient waiting?

PMID- 21957533
TI  - Watch your mouth.

PMID- 21957534
TI  - Chemical policy reform--nurses must say "Yes".

PMID- 21957535
TI  - Pharmaceutical waste problem solved, or not.

PMID- 21957536
TI  - Changing the healthcare menu.

PMID- 21957537
TI  - It's your right to be safe in your environment.

PMID- 21957538
TI  - Team work at the heart of perioperative nursing.

PMID- 21957539
TI  - Anevili deserves the spotlight.

PMID- 21957540
TI  - Fathers are family too!

PMID- 21957541
TI  - Respect for te reo Maori.

PMID- 21957542
TI  - Survey of nursing evidence website.

PMID- 21957543
TI  - Seeking honesty in politics.

PMID- 21957544
TI  - Who ate all the pies?

PMID- 21957545
TI  - Nurses have an ethical imperative to minimise procedural pain.

PMID- 21957546
TI  - Rongoa--its place in the health system.

PMID- 21957547
TI  - Theatre team learns to use checklist to make surgery safer.

PMID- 21957548
TI  - Throwing open the doors on theatre nursing.

PMID- 21957549
TI  - Nurses challenge the operating room culture.

PMID- 21957550
TI  - Valuing nurses leads to better patient care.

PMID- 21957551
TI  - Incontinence and retention--how the bladder misfunctions.

PMID- 21957552
TI  - Nursing a patient with Guillain-Barre syndrome.

PMID- 21957553
TI  - Public safety or patch protection?

PMID- 21957554
TI  - From nurse to organiser--a challenging transition.

PMID- 21957555
TI  - Chasing stroke knowledge.

PMID- 21957556
TI  - The impact of dialysis on rurally based Maori and their whanau/families.
AB  - Compared to non-Maori, New Zealand Maori are at a higher risk of kidney disease
      which can lead to End Stage Renal Disease (ESRD) and the consequent need for
      renal replacement therapy, including dialysis, to sustain life. This study was
      designed to explore the impact that dialysis has on Maori and their
      whanau/families. An interpretive approach was used. The purposive sample
      consisted of seven Maori clients having dialysis as outpatients while living in a
      rural area of Northland. Clients and their whanau/families were interviewed in
      2008. A number of themes summarising client perspectives were indentified from
      analysis of the responses. Despite their differing journeys to the point of
      requiring haemodialysis four basic themes were revealed: facing their fear;
      stress from having haemodialysis; learning, adjusting and changing their
      attitude; and individual needs. Understanding Maori clients' experience of
      haemodialysis provides insight regarding their requirements, most notably in
      terms of education and support. Recommendations from this study include the need
      for early referral and effective education to promote self-management - factors
      which, in turn, can influence quality of life and lead to more cost effective
      health care.

PMID- 21957557
TI  - A tripartite learning partnership in health promotion.
AB  - The shift in health care towards primary health services and health promotion
      requires nursing education to ensure students learn to practice in partnership
      with communities. In primary health care settings opportunities for students to
      learn the participatory communication skills required for collaborative practice
      have been found to be constrained by a range of factors. An innovative approach
      increasingly being reported is for nurse educators and students to work with
      groups in the community, for example with teenage mothers. In mental health this
      approach is common, with consumers willingly working with nurse educators and
      students to complement the experience students gain working alongside health care
      professionals. This paper describes a partnership between a New Zealand nursing
      programme and a community trust whereby nursing students together with youth
      enrolled at a local high school promoted health. The nursing students reported
      that the experience encouraged them to view their practice from the perspective
      of the young people with whom they were working, and to see their efforts in the
      school setting as part of the wider community's health. It is argued that this
      strategy successfully contributed to the students' acquisition of the
      collaborative skills required to develop nursing partnerships within communities.

PMID- 21957558
TI  - The clinical nurse specialist in New Zealand: how is the role defined?
AB  - New Zealand, like many countries, is developing new advanced nursing practice
      roles to meet emerging needs. While much has been written about the Nurse
      Practitioner (NP), the role of Clinical Nurse Specialist (CNS) remains relatively
      unexplored and lacks national definition. This paper reports the findings from
      research designed to investigate the role of the CNS and how it is defined by New
      Zealand District Health Boards (DHBs). The study sought to identify the current
      requirements and expectations for the CNS role and how it is defined in practice.
      In 2008, 15 CNS job descriptions were collected from eight DHBs throughout the
      country generating data that were treated both quantitatively and qualitatively.
      Overall, few areas of consensus were found regarding the essential requirements
      for the CNS role and there were inconsistencies in how the roles were defined,
      most notably concerning requirements for postgraduate qualifications and
      Professional Development Recognition Programmes. Thematic analysis of the
      documents generated four key areas relevant to the CNS role. These described the
      CNS as a leader, a clinical expert, a co-ordinator and an educator. The findings
      indicate that the CNS role is inconsistently defined in New Zealand, particularly
      with respect to the postgraduate qualifications required and what is meant by
      'expertise'.

PMID- 21957559
TI  - New school year resolutions.

PMID- 21957560
TI  - Gearing up for a new School year: what empowers you?

PMID- 21957561
TI  - Back to school: student athletes and injuries.

PMID- 21957562
TI  - Mentoring the new generation of school nurses.

PMID- 21957563
TI  - Why is a school health (wellness) advisory council important for school nursing
      practice?

PMID- 21957564
TI  - Mastering the metered-dose inhaler: an essential step toward improving asthma
      control in school.
AB  - School nurses can have significant cohorts of students with asthma. Effectively
      managing asthma in school can be challenging in terms of time, resources, and
      outcomes. A valuable focus for the school nurse is inhaled medication
      administration. Understanding the details required for optimal inhalation
      technique with metered-dose inhalers is the foundation for developing the skills
      to deliver and teach this vital aspect of asthma management. The school nurse can
      play a pivotal role in the partnership of asthma education that can benefit the
      student in school and at home.

PMID- 21957565
TI  - School nurses lead the team: successful relationships with families of children
      with diabetes.

PMID- 21957566
TI  - All about lunch!

PMID- 21957567
TI  - Medication error prevention in the school setting: a closer look.
AB  - Empirical evidence has identified that medication errors occur in the school
      setting; however, there is little research that identifies medication error
      prevention strategies specific to the school environment. This article reviews
      common medication errors that occur in the school setting and presents potential
      medication prevention strategies, such as developing medication error reporting
      systems, using technology, reviewing systems and processes that support current
      medication administration practices, and limiting distractions. The Standards of
      Professional Performance developed by the National Association of School Nurses
      identifies the need for school nurses to enhance the quality and effectiveness of
      their practice. Improving the safety of medication administration and preventing
      medication errors are examples of how nurses can demonstrate meeting this
      standard.

PMID- 21957568
TI  - Facilitating successful substitute school nurse programs: a multi-school
      roundtable.
AB  - Fortunate indeed are schools that have adequate school nurse-to-student ratios,
      let alone schools that also value and provide substitute registered nurses (RNs)
      in the absence of the contracted school nurse. In a recent article in the Journal
      of School Nursing, Vollinger, Bergren, and Belmonte-Mann discussed personnel who
      staff the school health office in the absence of the school nurse; the authors
      found substandard coverage in the majority of the schools. The article
      recommended, among other things, that school nurses engage in dialogue to
      encourage programs to increase the number of RN substitutes. The purpose of this
      roundtable article is to provide initial dialogue on this subject.

PMID- 21957569
TI  - Guidelines for youth sports safety.
AB  - With the beginning of each school year athletes of all ages are gearing up to
      play. The National Athletic Trainers' Association offers several important tips
      for consideration before a player begins formal participation, including
      information regarding pre-participation physicals; beating the heat; locker room
      cleanliness; emergency action plans; and exercising caution with head injuries,
      including new information concerning the difference between concussions in girls
      and boys.

PMID- 21957571
TI  - Promote thyself.

PMID- 21957570
TI  - Sports drinks and energy drinks for children and adolescents--are they
      appropriate? A summary of the clinical report.

PMID- 21957572
TI  - [Distribution of the different patterns of aging over the system of animal
      world].
AB  - Since the system of animal world reflects evolutionary trends, an analysis of
      distribution of patterns of aging over this system provides information on the
      causes of the formation of differences among them. In this paper the system of
      the main animal groups in form of a table is presented, and the distribution of
      patterns demonstrating minimum and maximum of aging is discussed. Meanwhile the
      colonial animals are considered as a "minimum of aging", the animals
      demonstrating drastic self-liquidation after reproduction are considered as a
      "maximum of aging" (the most well-known example is the pink salmon). It is shown,
      that as far as the degree of difference from the simplest ancestor increases in
      process of evolution, the increase of the manifestations of aging takes place.
      Slow aging of relatively simple organisms cannot be a direct source of measures
      to prevent aging of complex ones.

PMID- 21957573
TI  - [The regulated effect of the coded amino acids on the basic cellular processes in
      young and old animals].
AB  - The aspects of the regulatory effect of 20 coded amino acids on the basic
      cellular processes--proliferation and apoptosis--are discussed. This effect is
      performed due to the regulation by the amino acids of the specific genes at the
      levels of the transcription and translation. This leads to the triggering of the
      regulation of any cellular processes. The investigations in organotypic culture
      of the tissues of the different genesis have demonstrated that the different
      amino acids perform the cell proliferation or apoptosis. The group of low
      molecular mass hydrophile amino acids with the charge chains stimulated the cell
      proliferation in the tissues of mesodermal genesis. The other group of high
      molecular mass hydrophobe amino acids stimulated the cell proliferation in the
      tissues of ectodermal genesis. Thus, the coded amino acids are not only the
      structural elements of the proteins, but can participate in the regulation of the
      specific genes, controlling the cellular cycle. The number of the active amino
      acids is decreased in 2.7 times in the explants from the old rats, as compared to
      the young, reflecting the disturbances in the amino acid transport and gene
      expression by the aging.

PMID- 21957574
TI  - [Effects of relic microorganism B. sp. on development, gaseous exchange,
      spontaneous motor activity, stress resistance and survival of Drosophila
      melanogaster].
AB  - The effect of relic microorganism B. sp., living in severe environment of
      Siberian permafrost during thousands and millions of years, on development and
      stress resistance of Drosophila melanogaster has been studied. In manipulating
      with such objects with practically "eternal life span", molecular carriers of the
      unprecedented longevity potential and possibilities of their transmission to
      other biological objects should primarily be addressed. Here we discuss for the
      first time the influence of B. sp. application on development, survival, stress
      resistance and the gross physiological predictors of aging rate in D.
      melanogaster. To establish optimal and toxic doses, wide range of B. sp.
      concentrations were tested (1-500 million cells of B. sp. per 1 ml of the flies
      feeding medium). Surprisingly, no toxic effects of B. sp. could be registered
      even on such a "sensitive" model as the developing larvae. In fact, the rate of
      development, survival and body mass gradually increased with elevation of B. sp.
      concentration. The gain of higher body mass within shorter periods of development
      could indicate enhanced anabolic and/ or declined catabolic effects of B. sp.
      Higher motor activity and gaseous exchange rates were observed in imagoes
      developed on the mediums with B. sp. application. Survival of these flies at the
      heat shock (30 min at 38 degrees C) and ultraviolet irradiation (60 min, 50W UV
      lamp) was increased, indicating elevated stress resistance, apparently due to
      stimulation of DNA-repair and chaperone-mediated protection of macromolecules.
      Further research is clearly warranted to identify more efficient anti-stress and
      antiaging preparations and schemes of B. sp. application on models of laboratory
      mammals and human cell cultures.

PMID- 21957576
TI  - [The role of matrix metalloproteinases in human thymus aging].
AB  - The use of immunohistochemical method enabled to obtain for the first time
      expression ferments of extracellular matrix MMP2 and MMP9 in human thymus.
      Expression of matrix metalloproteinases is discreased in thymus of old age people
      in comparison with middle age people. These data testify to the important role of
      metalloproteinases 2 and 9 in extracellular interaction and proliferation
      activity in thymus aging.

PMID- 21957575
TI  - [Thymus and adaptive changes of bone marrow cell composition in animals of
      different age].
AB  - The influence of thymus removal or administration of thymalin, thymic peptide
      factor, on number of cells-precursors for colonies of fibroblasts (CFC-F) and for
      granulocyte-macrophageal colonies (CFC-GM), CD(4+)-cells in bone marrow in CBA
      mice of different age in some seasons was investigated. It was shown that in
      adult mice the orientation of influence thymic activity modulation on amount of
      these types cells is dependent from seasons. It was shown the season possibility
      of direct effect of thymic stroma supernatant, in which was thymic serum factor
      (FTS), or the synthetic FTS on the amount of CFC-F and CFC-GM in bone marrow of
      adult mice; in old mice thymic supernatant increased in vitro the amount of
      CD(4+)-cells. FTS level in old mice increased after administration of thymalin,
      the rhythm of CD(4+)-cells number in bone marrow and of corticosterone serum
      content restored.

PMID- 21957577
TI  - [Influence the water deprivation and alpha-tocopheroli acetates on the expression
      of apoptosis regulator proteins].
AB  - We revealed ontogenetic features in apoptosis level, apoptosis signal proteins
      expression, antioxidant (alpha-tocoferoli acetate) effects in neurons of
      magnocellular hypothalamic centers of BALB-c mice. It was obtained that water
      deprivation stress leads to apoptosis initiation of neurons in both age groups.
      Stress-protected action of alpha-tocoferoli acetate was more significantly in
      young mice compared to old ones. In our subsequent work (immunocytochemical
      reactions) we obtained further regular occurrences. Dehydration leads to increase
      of proapoptotic protein Bax synthesis in hypothalamic neurosecretory cells in
      young mice and in age-independent manner, this stress leads to decrease of
      antiapoptotic proteins Bcl-2 and Mcl-1 synthesis. So, the apoptosis level
      increases. More significant antiapoptotic action of alpha-tocoferoli acetate in
      stress condition in young mice is obviously connected with quick reaction of
      compensatory mechanisms (low expression of proapoptotic proteins p53, Bax and
      high expression of antiapoptotic protein Bcl-2).

PMID- 21957578
TI  - [The definition of chemiluminescence intensity in experimental model of premature
      senescence].
AB  - The diagnostic possibilities of chemiluminescence's intensity research for
      premature senescence prognosis are described in this article. The definition of
      chemiluminescence's intensity enables to reveal the individuals stable to
      processes of premature senescence in the model of acute radiation.

PMID- 21957579
TI  - [Surface architectonics and cytoskeleton state of different age rats' thymocytes
      exposed to peroxynitrite].
AB  - To reveal the role of aging in the changes of immune system cells response to
      proinflammatory (oxidizing) agent we have studied peroxynitrite (30 microM)
      influence on the cell surface layer structure of different age rats' thymocytes.
      In the absence of proinflammatory agent, there were no significant changes in
      morphological and topological parameters of thymocytes from the rats at 3 and 8
      months of age. According to atomic force microscopy data, peroxynitrite
      stimulates actin cytoskeleton structures assembly in thymocytes from 3-month rats
      but inhibits it in cells from 8-month rats. Obtained results make clear the
      difference between the immune system responses in inflammatory processes of young
      and old organisms.

PMID- 21957580
TI  - Brain proteoglycans in postnatal development and during behavior decline in
      senescence-accelerated OXYS rats.
AB  - Proteoglycans (PG) are involved in the brain development as well as in the
      pathogenesis of age-related neurodegenerative disorders but underlying mechanism
      remains poorly understood. We showed that senescence-accelerated OXYS rats are
      suitable model of age-related cerebral dysfunctions. Here the content and
      composition of PG in the postnatal development and during behavioral decline were
      examined in the brain of OXYS and Wistar(control) rats at the ages of 1, 7, 14
      days and 1, 2 and 14 months. Thereafter behavior in open field (OF) and elevated
      plus maze (EPM) was investigated. Data confirmed the absence of differences in
      the performance in tasks between Wistar and OXYS rats at the age of 1 month and
      showed faster age-related anxiety-like behavior decline in OXYS rats. The
      distribution of PG and the extent of their sulfation undergo dramatic and rapid
      changes in the brain during postnatal development both in Wistar and OXYS rats.
      Significant differences in these parameters appeared in the period of development
      of behavioral decline in OXYS rats. In contrast, no interstrain differences were
      revealed in the content and composition of PG in 14-month-old rats when behavior
      deteriorations are already developed. The results suggest that behavioral
      deterioration in OXYS rats occurs against the background of altered composition,
      quantity and glycosaminoglycans (GAG) sulfation.

PMID- 21957581
TI  - [Effect of expression of IL-6 cytokines in renal tissue on clinical and
      morphological picture of diseases in patients over 60 years with IgA
      nephropathies].
AB  - In this paper we analyzed the expression of cytokine IL-6 in biopsy tissue of the
      kidneys in IgA-nephropathy patients in different age groups, its relationship
      with clinical and morphological picture of the disease. The study showed that IL
      6 affects the formation of histopathological changes in kidney tissue and does
      not depend on the age of the patient. Given that the duration of the disease
      affects the expression of IL-6 expression in glomeruli (regardless of age of the
      patient) the role of IL-6 in the progression of the disease is confirmed.

PMID- 21957582
TI  - [The estimation of risk factors of the atherosclerosis in persons over 60 years
      of autochthonal and non-indigenous nationalities with the ischemic heart disease
      old living in the far north].
AB  - The study assessed the ethnic, age, gender distinctions on risk factors between
      elderly, senile age and long-livers male and female of autochthonal and non
      indigenous nationalities with ischemic heart disease. 354 patients aged from 60
      till 106 years comparable on age and gender data, had been included in research.
      There were 2 basic groups considering the ethnic implement (autochthonal and
      nonindigenous citizens); 3 groups considering the age characteristics (elderly,
      senile age and long-livers); gender groups - male and female. As a result of
      study the ethnic, age, gender differences were revealed on the primary risk
      factors such as arterial hypertension, blood lipids, body mass index, smoking and
      left ventricular hypertrophy.

PMID- 21957583
TI  - [Nitric oxide and human aging].
AB  - More than in 500 17-21-year-old medical students stress reactivity (SR),
      biological age (BA), arterial pressure (AP) and nitric oxide (NO) metabolites
      excretion to the alveolar air [nitrates and nitrites concentration (NNC) in
      alveolar condensate] were determined in rest and before examinations during 1995
      2204. AP, BA and NNC were measured in various trimesters of individual year (IY,
      the period from one person's birthday to another). During this period girls' AP
      changes insignificantly. The AP of youths is higher than in girls and increases
      during IV-IY trimester (10-12 months after birthday). The youths NNC decreases
      from the II to the IV-IY trimesters, but in girls there is a tendency to NNC
      increase during the IV-IY trimester their NNC negatively correlates (r = -0,34)
      with their systolic AP Among youths and girls with equal AP, NNC is significantly
      higher in girls. NNC decreases with the SR rise; this decrease develops during
      the examination stress too, but in girls NNC decrease is less. BA in youths is
      higher than in girls and increases during the IV-IY trimester. In youths BA
      negatively correlates (r = -0,60) with NNC. Taking into mind the "stress theory"
      of aging (P. Parsons, 1995) our data may be a basis to assumption that nitric
      oxide is a "molecule of anti-aging".

PMID- 21957584
TI  - [Coronarography in coronary heart disease in elderly patients of behavioral type
      A].
AB  - 177 patients aged 32 to 74 years with CHD were examined. The data on angiographic
      situation and connection between the condition of coronary arteries and
      behavioral singularity of old-aged CHD patients of different behavioral types are
      revealed. The results of angiographic examination of heart vessels in old-aged
      CHD patients of behavioral type A are shown.

PMID- 21957585
TI  - [Debitometry in outcome forecasting of lower limb artery reconstructions in
      elderly and senile patients].
AB  - We use perfusion roller debitometry as an original method of flowmetry. Roller
      pump enables to support perfusion pressure at constant level. This way, we can
      estimate the flow rate of distal vascular throughput at aorto-femoral and femoro
      popliteal reconstruction for success of operation.

PMID- 21957586
TI  - [Age features of the modular condition of blood in persons of senile age at
      physiological aging].
AB  - Study of the peculiarities of blood aggregation in the elderly with physiological
      aging is of particular interest. There is a significant contribution to the
      development of age involution decrease in endothelial function (reducing the
      synthesis of prostacyclin, decreased antiaggregation activity of the vascular
      wall), diastolic dysfunction of the left ventricle, increased rigidity of
      vascular wall and remodeling microvasculature. The complex estimation of blood
      aggregation and identification of features of interaction of individual factors
      in elderly patients has important clinical implications.

PMID- 21957587
TI  - [Morphological changes in atria at sudden cardiac arrest in elderly patients with
      coronary heart disease].
AB  - The morphological changes of left atrium at sudden cardiac death in elderly and
      senile persons are given in this paper. The results testify that in persons of
      elderly and senile age with ischemic heart disease the developing changes in the
      heart muscle atrium create favorable conditions for occurrence of arrhythmias,
      fibrillations and sudden death, which should be taken into account at this
      pathology.

PMID- 21957588
TI  - [Application thymogen for preoperative preparation of elderly patients with tumor
      processes in abdominal cavity].
AB  - A double-blind, randomized, placebo-controlled study of the efficacy of Thymogen
      preparation for elderly patients for surgery on the solid tumors in abdominal
      cavity and retroperitoneal space was carried out. The drug has been administered
      by intranasal instillation of 100 mg once a day for 7 days before surgery. The
      isotonic sodium chloride solution for the placebo group in the same scheme was
      used. The preoperative use of Thymogen proved to be useful to restore the
      structural and functional parameters of cellular immunity. Immunomodulatory
      therapy resulted in the significant decrease in the number and range of post
      operative complications and the shorting of the postoperative period.

PMID- 21957589
TI  - [The clinical pathology of polymorbidity in geriatrics practice].
AB  - The original data about phenomenon of polymorbidity in geriatrics practice are
      presented in the article. Most often ways of the development of polymorbidity and
      their clinical outcomes are discussed.

PMID- 21957590
TI  - [Efficiency of rehabilitation of elderly and senile patients after an ischemic
      stroke].
AB  - Productivity of a wide medical rehabilitation in 296 patients who have had an
      ischemic stroke was studied. In the period of rehabilitation treatment 186
      patients of 70-84 years composed the basic group, 110 in the control group were
      of 33-60 years. Clinical, social, psychological indicators in dynamics were
      compared; results of variety of tool and laboratory researches were estimated.
      Possibility of high efficiency of medical rehabilitation in elderly and senile
      age is stated. This efficiency depends on expressiveness of impellent defect, the
      period of a stroke, somatic diseases and on depressive infringements. Positive
      shifts in character of bioelectric activity of a brain and also activation of non
      vascular link of a cerebral metabolism in comparison with vascular one can serve
      as prognosis criteria of success of rehabilitation of the elderly.

PMID- 21957591
TI  - [Definition of rate of biological aging at vibration disease].
AB  - The article presents results of definition of biological aging rate at vibration
      disease caused by the influence of local and general vibration, at I and II stage
      of disease; a role of vibrating influence in acceleration of biological aging of
      people working in the conditions of vibration is underlined.

PMID- 21957592
TI  - [Biological age and the pain syndrome at diabetic polyneuropathy].
AB  - Patients with diabetic polyneuropathy were examined to study their biological
      age, rate of aging and pain syndrome. More rapid rate of aging was revealed in
      patients with diabetic polyneuropathy and pain syndrome. Using Duloxetin and
      Gabapentin is reliable to decrease the display of pain syndrome in diabetic
      polyneuropathy patients. Against the background of pain syndrome therapy the rate
      of aging is noticed to decrease along with the regression of pain syndrome. The
      medicines of Duloxetin and Gabapentin which are used during depression and
      epilepsy protect against aging.

PMID- 21957593
TI  - Nonsteroidal anti-inflammatory drugs: as inappropriate pharmacotherapy in the
      elderly?
AB  - Nonsteroidal anti-inflammatory drugs (NSAID) are one of the most used groups of
      drugs in elderly population. The aim of this study was to establish the frequency
      of reported disorders while using NSAID in elderly patients. A multi-centric
      study was conducted with a standard questionnaire for all geriatrician
      outpatients who were using NSAID. It has been found that out of 421 patients, 320
      reported some kind of disorder; 287 of them used other drugs beside NSAID, 33
      used only NSAID during the study. It has been concluded that frequency of
      reported disorders was significantly higher among patients who used another drug
      beside NSAID, and statistically most frequent reported disorders were
      gastrointestinal.

PMID- 21957594
TI  - GAD antibodies in T1D and LADA--relations to age, BMI, c-peptide, IA-2 and HLA
      DRB1*03 and DRB1*04 alleles.
AB  - The determination of GADA may be useful for clinical classification of diabetes
      mellitus (DM) in clinically unclear cases. This GADA positivity may persist in
      any diabetics Type 1 Diabetes Mellitus (T1D) with an onset in adulthood and Late
      Autoimmune Diabetes of Adults (LADA) many years after appearance of DM. The study
      was aimed at comparing the levels of GADA between both diabetic subsets with
      their clinical parameters, age of onset DM, period of insulin need, body mass
      index, HbA1C, fasting and postprandial C-peptide, risky HLA-DRB1* alleles,
      occurrence of micro- and macrovascular diabetic complications. Further analysis
      of GADA titers in different time consequences to the development of DM and
      relations to IA-2 were made. In the study, we included 130 diabetics with an
      onset of diabetes (T1D or LADA) 35+ y. who were hospitalized and afterwards long
      term observed in the diabetological outpatient department. Out of this number
      there were 62 men and 68 women of the average age 65.5 +/- 14.0 y. (range 35-93
      y.). 54 were assessed as the T1D patients and 76 as the LADA ones. Patients of
      the T1D subgroup were GADA positive 22 times and of the LADA subgroup 21 times.
      LADA 2 patients that were GADA negative were more obese than GADA positive LADA
      diabetics (p < 0.01). Also postprandial C-peptide was higher in LADA patients
      GADA negative (p < 0.05). Other clinical characteristics were without
      statistically significant differences. We found in our diabetic patients a
      relation between alleles HLA-DRB1*03 and particularly combination with HLA
      DRB1*04 with positive GADA levels. In the GADA negative group obesity, coronary
      heart disease, hypertension, syndrome of diabetic foot and dyslipidaemia appeared
      more frequently (OR = 2.8; 3.1; 6.2 and 2.4). We found no significant differences
      in observed parameters--comparison GADA positivity and negativity according to
      the duration of DM. GADA positive were even 10 y. duration 16 times and after 20
      y. even 6 times. Recent DM had positive GADA in 11 cases and 13 cases of recent
      DM had GADA negative. IA-2 antibodies were positive (> 1.0 U/ml) 18 times
      altogether and always with positive GADA, but only 7 times in recent DM. The
      presence of elevated GADA identifies patients unequivocally suitable for early
      insulin therapy. Our observations and experiences confirm that GADA can be found
      increased after more than 10-20 years duration of DM, although in decreasing
      trend.

PMID- 21957595
TI  - [Age peculiarities of clinical course of occupational chronic obstructive
      pulmonary disease].
AB  - The article is devoted to analysis of the problem of lung diseases due to
      industrial dust exposure in Kursk region and to studying the clinical features of
      the most widespread occupational respiratory disease--occupational chronic
      obstructive pulmonary disease, among patients of various age groups. It is shown
      that the development of dust-induced bronchoobstructive diseases provokes
      infringement of physiological lungs aging and in clinical course of the disease
      in elderly and senile age has its features.

PMID- 21957596
TI  - [Features of neurologic semiotics at chronic obstructive pulmonary disease].
AB  - Chronic obstructive pulmonary disease (COPD) is actual pathology, when it forms
      the mixed hypoxemia. In the conditions of a chronic hypoxemia structures of
      organism with high level of metabolic processes, namely brain tissues, suffer.
      Character of defeat of the central nervous system at that pathology is
      insufficiently studied. In this article we studied and analysed the presence of
      such changes as depression, anxiety, cognitive impairment and features of
      neurologic semiotics at COPD in 50 patients.

PMID- 21957597
TI  - [Aging eyelid: clinical, morphological manifestations and peculiarities of
      microcirculation].
AB  - Morphological study of eyelid biopsy tissues with varying degrees of age-related
      changes revealed sclerosis, infiltration, expansion and the convoluted
      configuration of the walls of blood vessels, stasis, reflecting microcirculation
      disturbance in the skin. Decrease in elasticity, elasticity and skin turgor in
      aging eyelids is largely due to the thinning, randomly distributed bundles of
      collagen and a decrease in the number or total absence of elastic fibers. In 31
      patients with blepharohalasis laser Doppler flowmetry revealed a failure in the
      neuromuscular regulation of vascular tone, which is a manifestation of chronic
      stagnation in the microcirculatory bed. Revealed changes in the morphological
      structure of eyelid skin and microcirculatory bed confirm the trophic
      disturbances and congestion occurring in the skin of eyelids with aging.

PMID- 21957598
TI  - [The peculiarities of adaptation of a woman organism to the conditions of the
      Altai medium height altitude zones].
AB  - A comparative analysis on the morphological features, the duration of the
      reproduction period and antioxidant activity of blood plasma of the female
      population living in the Altai low and medium height altitude zones has been
      conducted. As a result we have discovered that women living in the unfavorable
      conditions of medium height altitude zones have a tendency to raise the body mass
      index, a shorter reproduction period and lower level of blood plasma antioxidant
      activity.

PMID- 21957599
TI  - Critical reflections on families of older adults.
AB  - Families are a central feature in the debate about how societies will face the
      challenges of population aging. In much of the contemporary discourse about
      families they are viewed as fully responsible for the care and support of their
      older members, with national differences in whether this responsibility is seen
      as a societal obligation or an unreasonable burden. Researchers and policy makers
      have expressed rising concerns about how structural changes to families and their
      increasing geographic mobility may threaten their caring capacity. Across regions
      and countries, there is considerable research on whether older adults are
      embedded in stable family networks from which they can draw support if needed. A
      more muted theme about the place of families in the lives of older adults places
      older persons as agents rather than passive recipients in their families. Within
      this body of literature, there is evidence of the important role of older adults
      in strengthening cohesion in families, fostering generational connections and
      caring for younger family members. The transfer of resources from older to
      younger members is an important feature in both marginalized and affluent
      families in different regions of the world. It illustrates the way that older
      adults provide stability to their families in the face of rapid social change. In
      this paper an overview is presented of the international literature on these
      complex issues of the place of families in the lives of older adults. Myths about
      families, regional variation in beliefs about their roles and obligations, and
      evidence of family structure and household composition of older persons are
      addressed and regional differences considered.

PMID- 21957600
TI  - [Obtaining the Impact Factor by Ginekologia Polska].
AB  - Scientific journals are ranked and evaluated to measure their relative importance
      and influence on science within a specific field. One of the tools most widely
      used to evaluate and compare journals is the Thomson Reuters Impact Factor In
      Poland a specific value of a scientist's Impact Factor is required for academic
      promotion. Ginekologia Polska was placed on the Master Journal List in 2008 in
      the result of changes introduced in 2007 by the new Chief Editor prof. Marek
      Spaczynski. In 2010, first time in its history the journal was listed in the
      Journal Citation Reports with the Impact Factor 0.367. The analysis of
      Ginekologia Polska contemporary value, as well as of prospects for its
      development was conducted on the basis of the Journal Citation Reports. In the
      light of the JCR data, Ginekologia Polska is a highly regarded title compared to
      other Polish journals. Its value and importance is gradually growing.

PMID- 21957601
TI  - [Concentration of selected cytokines in women with premature rupture of membranes
      and preterm delivery--preliminary study].
AB  - INTRODUCTION: For years much attention has been paid to the possible role of
      cytokines in the etiology of preterm delivery (PTD) in relation to anticipation
      of delivery in women with premature rupture of membranes (PROM). There are no
      clear indications introducing this observation to clinical practice. The goal of
      this study was to evaluate interleukin-6 (IL-6), tumor necrosis factor alpha (TNF
      alpha), G-colony stimulating factor (G-CSF) concentration in serum of women with
      PROM in connection with the occurrence of the delivery MATERIAL AND METHODS: 35
      patients with PROM (average age 29.6 +/- 3.8 years, average time of gestation
      35.2 +/- 1.5 weeks) were analyzed. The pregnant women were divided into 2 groups:
      15 women delivered < 24 h and 20 women delivered > 24 h since the appearance of
      PROM. In both analyzed subgroups, the levels of IL-6, TNF-alpha, G-CSF CRP and
      leucocytosis have been compared. The concentration of IL-6, TNF-alpha and G-CSF
      in serum was measured by immunoenzymatic ELISA method, CRP concentration by
      immunoturbimetric method. RESULTS: In the whole group of women with PROM, the
      differences in average serum concentration of IL-6 before and after delivery
      (6.01 +/- 3.71 pg/mL and 7.98 +/- 3.44 pg/mL p < 0.05) and G-CSF (130.92 +/-
      110.32 pg/mL and 79.59 +/- 52, 13 pg/mL, p < 0,05) have been observed. Moreover,
      average TNF-alpha concentration before and after the delivery was 1.43 +/- 0.63
      pg/mL and 1.72 +/- 1.06 pg/mL (p > 0.05), respectively. It is particularly
      interesting that the authors have observed higher concentration of G-CSF in women
      who delivered within 24 h since PROM (147.05 +/- 103.88 pg/mL), if compared to
      the women who delivered after 24 h since PROM (118.81 +/- 115.71 pg/mL, without
      statistically significant difference p > 0.05). The same remark was connected
      with difference of IL-6 concentration in analogical groups of women (6.42 +/-
      4.14 pg/mL vs 5.71 +/- 3.42 pg/mL, p > 0.05). Equally interesting observation
      were statistically significant differences in G-CSF concentration before and
      after delivery (147.06 +/- 103,88 vs 74.67 +/- 46.84, p < 0.05) in the event of
      the delivery < 24 h since PROM, such as in IL-6 concentration (5.71 +/- 3.42 vs
      8.11 +/- 3.41, p < 0.05) in case of the delivery > 24 h since PROM. CONCLUSIONS:
      Statistically significant differences in IL-6, G-CSF, and CRP concentration
      before and after the delivery suggest the participation of these factors in the
      etiology of preterm delivery in women with PROM. The higher IL-6 and G-CSF
      concentration in women delivering within 24 h since the appearance of PROM
      suggest that these cytokines could be involved in the processes leading to
      delivery Statistically significant differences in IL-6 and G-CSF concentration
      before and after the delivery in a group of women delivering < 24 h or > 24 could
      indicate an important contribution of changes in proportions of these cytokines
      in PTD the etiology in PROM.

PMID- 21957602
TI  - Adrenomedullin mRNA expression in placenta of preeclamptic women.
AB  - INTRODUCTION: Adrenomedullin (ADM) is indicated to be a biologically active
      polypeptide released by endothelium with strong hypotensive, long-acting
      vasodilatator properties. It is suggested that development of preeclampsia is
      partly related to decreased ADM influence on blood vessels. AIM: The purpose of
      this study was to evaluate the adrenomedullin mRNA expression in placenta of
      preeclamptic women and additionally to assess the correlation between ADM mRNA
      expression and -1984A > G ADM gene polymorphism. MATERIAL AND METHODS: 26
      preeclamptic (PE), 20 with gestational hypertension (GH) and 43 normotensive
      healthy pregnant women have been involved into the study. The placenta samples
      were collected instantly after delivery from the central part of maternal side.
      The ADM gene expression was measured with the real-time polymerase chain reaction
      (rt-PCR). The results were standardized according to the reference glyceraldehyde
      3-phosphate dehydrogenase (GAPDH) gene. The -1984A > G ADM gene polymorphism was
      determined by PCR/RFLP assay RESULTS: Lower expression of ADM mRNA in PE group
      (0.881 +/- 0.254 vs. 1.039 +/- 0.391 in controls, ns) has been investigated. In
      PE group the placental ADM mRNA expression was slightly higher at women carrying
      AA genotype (0.890 +/- 0.263 vs. 0.842 +/- 0.231, ns). In the control group
      higher placental ADM mRNA expression in women with AG + GG genotype of -1984A > G
      ADM gene polymorphism (1.249 +/- 0.431) in comparison to women carrying AA
      genotype (1.036 +/- 0.356, ns) was observed. The study also revealed negative
      correlation between placental ADM mRNA expression and systolic blood pressure in
      hypertensive pregnant women (p = 0.020). CONCLUSION: Reduced mRNA expression for
      ADM in the placenta connected with reverse correlation of systolic blood pressure
      in preeclamptic women suggests the significant role of disturbances in placental
      secretion of ADM in etiology of preeclampsia.

PMID- 21957603
TI  - [Analysis of the indications for the caesarean section delivery for very low
      birthweight neonates (< 1500 g) delivered in I department gynecology and
      obstetrics, Medical University in Lodz in 2006-2010].
AB  - Despite better care pregnant women receive nowadays, preterm birth and
      prematurity remain to be the reason of many complications and high mortality of
      neonates. OBJECTIVE: The goal was to analyze the indications for cesarean
      sections delivery for very low birthweight (<1500 g) newborns delivered in the I
      Department Gynecology and Obstetrics, Medical University in Lodz. MATERIAL: The
      data from 560 preterm caesarean sections were analyzed. Detailed analysis
      referring to 120 cesarean sections resulting in deliveries of very low
      birthweight neonates was performed. Maternal age, parity neonatal weight and
      gestational age were assessed. The authors also assessed the number of cesarean
      sections performed for extremely low birthweight newborns, in particularly years
      and the rate of the indications in the groups of gestational age. RESULTS: The
      greatest number of the cesarean sections was done between 26-35 years of age of
      the patients (68,4%) in 28-32 weeks of gestation (53,3%). The rate of cesarean
      section performed for very low birthweight neonates was 2,3% of preterm caesarean
      sections. Fetal growth restriction (IUGR) and the symptoms of intrauterine
      hypoxia were the indications for cesarean sections in 33,4%, multiple pregnancy
      in 17,5%, abnormal fetal presentation in 15,8%, intrauterine infection in 13,3%
      and placental abruption in 11,7% of cases. The rate of the other indications was
      11,7% of cases. CONCLUSIONS: In our material the most frequent indication for the
      cesarean section for very low birthweight neonates was fetal growth restriction
      with the symptoms of intrauterine hypoxia.

PMID- 21957604
TI  - [Causes of stillbirths and perinatal death in Poland between 2007-2009].
AB  - INTRODUCTION: There has been significant improvement in perinatal care in the
      last two decades. Indicators representing the status of perinatal care are the
      frequency of stillbirths and deaths in the early postnatal period. In recent
      years the level of perinatal care of the mother remains stable while the level of
      perinatal deaths have been slightly decreasing. AIM: The aim of this study was to
      evaluate the frequency of stillbirths and early neonatal deaths. MATERIAL AND
      METHODS: The study included Polish women who delivered in 12 regions of Poland
      between 2007-2009. Data were collected with the use of MZ 25 forms. ISSUES: There
      were 1214818 children delivered in Poland in years 2007-2009. Our data were
      collected in 12 regions, what amounts to about half of all deliveries. Perinatal
      death rate decreased during the last 12 years from 10,8 per thousand in year 1999
      to 7,6 per thousand in 2008; 7, 19 per thousand in 2009; 6,79 per thousand in
      2010, what was 4 per thousand in 12 year. 2484 deaths were divided into 9 groups
      according to ICD- 10 causes of deaths. 26,6% causes of deaths were unknown.
      Malformations were causes of 24% deaths, placental disorders--12%. Perinatal
      deaths of newborns--1412 cases were caused mostly by malformations--30,8%,
      disorders during pregnancy--35,4% and disorders of the pulmonary system--13%.
      CONCLUSIONS: Detailed analyses of each neonatal death and perinatal death in the
      first few hours after the deaths, performed by in the team of obstetricians and
      neonatologists, with specialists like pathomorphologists and geneticians, have
      great impact on the final correct cease description and determining the cause of
      death. It is also helpful in educating doctors and preparing proper equipment for
      hospitals. Our data showed the necessity to involve changes in perinatal care
      system. In will be helpful in early detections of malformations and
      redistribution of pregnant women with sick fetuses to Il level hospitals. There
      exists a need to introduce a compulsory detailed analyses of perinatal deaths in
      obstetrical wards.

PMID- 21957605
TI  - 18F-FDG PET-CT and USG/CT in benign and malignant ovarian tumors with
      postoperative histopathological correlation.
AB  - OBJECTIVES: The role of 18F-FDG (18F fluorodeoxyglucose) PET/CT** (Positron
      emission tomography) in the diagnosis, treatment and follow up of benign and
      malignant ovarian tumors had been investigated previously. The objective of the
      following study was to evaluate the predictive value of PET/CT in benign and
      malignant ovarian tumors and compare with computerized tomography and post
      operative pathology. MATERIALS AND METHODS: In this retrospective study a total
      of sixty nine cases with benign or malignant pelvic masses underwent laparotomy
      at our clinic. Postoperative pathology of the patients was recorded and PET/CT
      results were compared with ultrasonography computerized tomography and
      postoperative pathology. RESULTS: The ROCs and AUCs values four predictors were
      shown in Figure 1. The AUCs (95 % CI) values calculated for CA 125,
      ultrasonography (USG), PET/CT and CT were as follows: 0.855 (0.752-0.958), 0.703
      (0.540-0.866), 0.681 (0.514-0.848) and 0.631 (0.463-0.799) respectively CA 125
      has the highest AUC value in order to predict the malignant potential of the
      patient. USG has the highest AUC value between the imaging techniques, following
      PET/CT and CT CONCLUSION: According to this study among four modalities that
      distinguish malignant potential preoperatively; CA 125 is the best parameter USG
      and PET provide similar benefits in detecting malignant ovarian masses
      preoperatively. Both of these parameters are superior to CT Combination of CA
      125, USG and PET/CT may be useful in detecting malignant ovarian masses
      preoperatively resulting in less invasive surgeries.

PMID- 21957606
TI  - [The diagnostic value of cytology and colposcopy in women with cervical
      intraepithelial neoplasia].
AB  - OBJECTIVES: The aim of this study was to determine the diagnostic value of
      cytology and colposcopy in women with CIN. MATERIAL AND METHODS: The study
      involved 687 women with histologically confirmed CIN. The colposcopic images were
      recorded and archived, followed by computer analysis. Pap smears were evaluated
      according to the Bethesda system. Statistical analysis was performed with
      Statistica PI ver 6,0 software. RESULTS: The Pap smears had a sensitivity of
      58,02% and 63,28% specificity in the diagnosis of CIN. Positive predictive value
      (PPV) for cytology was estimated at 75,38% and negative predictive value (NPV) at
      43,75%. The study showed 89,21% sensitivity and 98,87% specificity of colposcopy
      in the diagnosis of CIN. The positive predictive value (PPV) for colposcopy was
      estimated at 99,35% and negative predictive value (NPV) at 82,55%. CONCLUSIONS:
      1. Diagnostic value of the Pap smears in the diagnosis of cervical
      intraepithelial neoplasia (CIN) is limited. 2. Colposcopy has a high sensitivity
      and specificity in the diagnosis of CIN.

PMID- 21957607
TI  - [Neonatal outcome after cesarean section].
AB  - Cesarean section is the most commonly performed procedure all over the world.
      Both American and European data reveal constant and steady increase of
      pregnancies resolved by a cesarean section. The reasons include: growing number
      of medical indications or requests of the pregnant women. Regardless of the fact
      that elective cesarean section decreases the risk of intrauterine hypoxia,
      meconium aspiration and injury during labor it remains a significant risk factor
      for respiratory failure in the course of transient tachypnea of the newborn,
      infant respiratory distress syndrome and pulmonary hypertension, both for term
      and late preterm infants. As a consequence, the infant requires a prolonged stay
      in the intensive care unit, together with advanced and often expensive medical
      procedures such as mechanical (often high-frequency) ventilation, nitric oxide
      therapy and extracorporeal membrane oxygenation. The American Association of
      Obstetricians and Gynecologists and the European Association of Perinatal
      Medicine recommend for a cesarean section due to medical indications to be
      performed after 39 weeks gestation, preferably after uterine contractions
      started, and elective cesarean section, particularly if there are indications to
      finish the pregnancy before 39 weeks gestation, after lung maturity has been
      assessed (in other case steroids ought to be administered prenatally to mature
      the lung muscles). That includes also cases of elective cesarean sections
      performed due to previous cesarean sections, which are the most frequent reasons
      for repeating procedure. The recommendations also restrict the indications for
      cesarean section in case of significant prematurity what in turn is connected
      with more restricted indications for resuscitation of extremely premature infants
      and babies with extremely low birth weight.

PMID- 21957608
TI  - The importance of cryosurgery in gynecological practice.
AB  - Cryosurgery is a destructive technique that was introduced to gynecology in the
      late 1960s to treat C/N (cervical intraepithelial neoplasia). Tens of thousands
      of patients have been treated with cryotherapy which has proved to be a
      predictable, reliable treatment technique, with limited side effects and
      morbidity. This method is used to treat cervical, vaginal, endometrial and vulvar
      lesions. This study aims at determining the current state of knowledge on the
      place of cryosurgery (cryotherapy) in gynecological practice. Research was
      carried out to find current data on indications, contraindications, techniques of
      treatment and equipment necessary to perform cryosurgical procedures in
      gynecology. Cryosurgery is a safe, relatively inexpensive and easy to perform
      procedure for treating women with lower genital tract pre-malignant diseases
      without impairing their fertility.

PMID- 21957609
TI  - [Pregnancy in a woman with chronic renal failure--the case of two successfully
      completed pregnancies and the review of the literature].
AB  - Together with the prolongation and improving the quality of life of young women
      with chronic renal failure (CRF), procreation becomes an important issue.
      Pregnancies in women on renal replacement therapy are associated with an
      increased risk of health complications, both for mothers and for fetuses. Medical
      management of pregnant women with CRF is a great challenge and requires a close
      co-operation of nephrologists, transplantologists, gynecologists and
      neonatologists. The complexity of problems in these particular pregnancies has
      urged us to describe the case of a woman with CRF who successfully delivered two
      babies. We also review the current state of knowledge on the topic. The first
      pregnancy five years after renal transplantation, was completed with the delivery
      of term newborn with Tetralogy of Fallot. Also the second pregnancy on
      hemodialysis therapy was finished by the birth of a healthy neonate at term. The
      described case indicates that the gynecologists should be prepared for the
      challenge of the care for pregnancies in women suffering from chronic renal
      failure on renal replacement therapy.

PMID- 21957610
TI  - [Obstetric consequences of uncontrolled gestational diabetes--a case study].
AB  - This paper presents a case of a pregnant woman who was admitted to the obstetrics
      and gynecology department because of a new onset of uncontrolled diabetes in 27
      weeks gestation. The maternal and fetal diabetic complications suggested a
      chronic character of the disease which must have been undiagnosed before
      pregnancy. Many of the co-existing infections caused a life-threatening
      ketoacidosis. Fortunately with the adequate treatment it was possible to ensure
      appropriate birth weight of the newborn baby despite the ultrasound markers for
      LGA (Large For Gestational Age) observed during pregnancy. Intensive insulin
      therapy was obligatorily continued by the mother after the delivery.

PMID- 21957611
TI  - [The first successful fetal aortic balloon valvuloplasty in Poland].
AB  - Prenatal aortic valvuloplasty is performed only in few perinatal centers in the
      world. Critical aortic stenosis which can lead to hypoplastic left heart syndrome
      or severe fetal heart failure with nonimmune hydrops is an indication for this
      procedure. Prenatal intervention can change the natural course of the disease.
      Authors present the first successful fetal balloon aortic valvuloplasty in
      Poland. It was performed in a 29-week fetus with critical aortic stenosis, severe
      impairment of left ventricular function, heart failure and fetal hydrops. After
      successful intervention, without any complications, left ventricular function and
      fetal condition improved gradually Effective fetal intervention was possible
      after few months of preparation and building a team of specialists. This is the
      first successful fetal cardiac intervention in Poland, which opens the way to the
      new era of fetal cardiology and hopefully will lead to improve results in
      children with this critical heart defect.

PMID- 21957612
TI  - [Epilepsy surgery--what is required from anesthesiologist].
AB  - The review contains brief description of modem anesthetic approaches used in
      intractable epilepsy surgery. The authors describe main types of neurosurgery
      operations for intractable epilepsy, as well as the basic anesthetics and
      anesthetic plans and their influence on the intraoperative ECoG. Another issue
      raised is awake craniotomy - an anesthetic method with intraoperative emergence
      for verbal contact between patient and psychologist. We conclude that epilepsy
      surgery is one of the neurosurgery fields where anesthesiologist can
      significantly affect the outcome of the operation.

PMID- 21957613
TI  - [Comparision of stress response severity during intravenous, inhalation and
      combined anesthesia (inhalation plus local) for pituitary transsphenoidal
      adenomectomy].
AB  - Transsphenoidal pituitary surgery is usually accompanied by severe hemodynamic
      stress response which is hardly treated with fentanyl. The main goal of the study
      is to compare anesthetic methods for endonasal endoscopic transsphenoidal
      pituitary adenomectomy and single out the most effective way of reducing or
      preventing the stress reaction. 65 patients underwent endonasal endoscopic
      transsphenoidal pituitary adenomectomy. In all the patients general an- esthesia
      was induced with propofol. Analgesia was provided by phetanyl boluses. The
      patients were divided into three groups. In the first group of patients TIVA with
      propofol-TCI was used. In the second group of patients anesthesia was maintained
      by N20 plus sevoflurane. The third group of patients received an additional
      bilateral endoscopic mucosal 2% lidocain 5 ml infiltration of the pterygopalatine
      nerve branches zone. Pipecuronium was used for neuromuscular blockade. The
      simultaneous HR, ABP and metabolism increase were qualified as stress response.
      In the first and second groups of patients the maximum stress response was
      recorded on the stage of mucosal coagulation and on the opening of the blades of
      bivalve nasal speculum. No major difference in stress response severity was noted
      in these groups. In the third group stress response was significantly lower.
      According of the results of the study bilateral endoscopic mucosal lidocaine
      infiltration of the pterygopalatine nerve branches zone for anesthetic management
      of endonasal endoscopic transsphenoidal pituitary adenomectomy can be
      recommended.

PMID- 21957614
TI  - [Intracranial pressure changes during xenon anesthesia in neurosurgical patients
      without intracranial hypertention].
AB  - Xenon assures rapid awakening and stable hemodynamics, it also has some
      neuroprotective effect. This is the reason why it may become an anesthetic of
      choice in neurosurgery. Still there is little and controversial data on its
      impact upon ICP. This is the first study of xenon effect upon intracranial
      pressure, cerebral perfusion pressure and cerebrovascular reactivity during xenon
      anesthesia in neurosurgical patients without intracranial hypertension. We report
      a slight increase in intracranial and a slight decrease in cerebral perfusion
      pressure during xenon anesthesia and show that cerebrovascular reactivity is
      preserved. Thus we conclude that xenon anesthesia is safe for neurosurgical
      patients without intracranial hypertension.

PMID- 21957615
TI  - [Impact of xenon anesthesia on cerebral oxygenation and metabolism in
      neurosurgical patients].
AB  - In recent years the background for xenon anesthesia implementation in
      neurosurgery has been created. A variety of researches have been conducted though
      very few of them concerned xenon effect upon cerebral metabolism. We assessed
      cerebral oxygenation and cerebral metabolism during propofol anesthesia followed
      by xenon closed circuit anesthesia in neurosurgical patients. Xenon inhalation
      was marked by higher jugular vein saturation, oxygen content and glucose level
      and lower arterio-venous difference. We conclude that compared to propofol xenon
      improves cerebral oxygenation and decreases cerebral metabolism in neurosurgical
      patients.

PMID- 21957616
TI  - [Monitoring the depth of anesthesia in neurosurgical patients].
AB  - The study reports the results of monitoring the depth of anesthesia with BIS
      technology in 456 neurosurgical patients with different neurosurgical pathology:
      sub- and supratentorial tumors, aneurisms, arteriovenous malformations, spinal
      pathology, etc. BIS reflects hypnotic state of the brain during anesthesia in
      almost all the cases, except for bifon-tal surgical approach when sensor
      placement is impossible. BIS monitoring of the depth of anesthesia is most
      advantageous in the following cases: epilepsy surgery, spine surgery with
      neurophysiological monitoring, awake craniotomy, severe cardiovascular pathology,
      massive blood loss, neurosurgery in pregnant patients.

PMID- 21957617
TI  - [Thromboelastography as a method for preoperative assessment of hemostasis state
      in neurosurgical patients on long term aspirin therapy].
AB  - The hemostasis state was assessed by routine tests and TEG in 169 patients on
      long term aspirin therapy. According to TEG results all the patients were divided
      into three groups: normo-, hypo- and hypercoagulation. The aspirin therapy was
      interrupted in normo- and hypercoagulation groups, but the surgery was not
      postponed. In cases of hypocoagulation the aspirin therapy was also interrupted
      and the surgery was postponed for 3-5 days until TEG results normalized. Also the
      frequency of intracranial hemorrhagic complications was analyzed in every group.
      The results showed that despite the method used the hypocoagulation group had the
      highest rate of postoperative hemorrhage complications. Thromboelastography
      enables to assess hemostasis state in neurosurgical patients on long term aspirin
      therapy promptly and effectively.

PMID- 21957618
TI  - [Analysis of efficacy and safety of preventive analgesia with transdermal
      therapeutic system Duragesic Matrix in spine surgery].
AB  - The survey studies analgesic effect of postoperative therapy in two groups of
      patients with spinal disorders. In the first group the standard scheme with NSAID
      on demand was used. In the second group transdermal therapeutic system Duragesic
      Matrix was applied. The pain level (by pain level scale) as well as psychological
      status and IL-6 rate (a reliable indicator of surgical trauma and pain severity)
      were assessed before and after surgery. Transdermal therapeutic system Duragesic
      Matrix applied before surgery appeared to be more effective for analgesic therapy
      than standard scheme with NSAID on demand.

PMID- 21957619
TI  - [Secondary abdominal compartment syndrome in postoperative period in patients
      with tumors of sellar region].
AB  - The abdominal compartment syndrome (ACS) can lead to multiple organ dysfunction
      syndrome (MODS), sepsis and death. In neurosurgical patients ACS used to be
      interesting for specialists only in respect of its impact on ICP. However injury
      of diencephalic structures of the brain can theoretically cause ACS. The goal of
      the study is to assess the efficacy of conservative therapy and epidural
      anesthesia for ACS treatment in postoperative period in patients with tumors of
      the sellar region. 41 patients were enrolled in the study. The epidural
      anesthesia at T8-T9 level by bupivacaine was applied for three days in the case
      of ACS development and ineffective conservative therapy. Intra-abdominal
      hypertension (IAH) developed in 28 cases, ACS - in 9. IAN usually revealed itself
      on the second day after surgery, ACS - on the 3rd-6th day. Gastrointestinal tract
      paralysis developed earlier than IAH and continued longer than IAH. Conservative
      therapy was effective only in every third patient with ACS. Epidural anesthesia
      was used in 4 cases and appeared effective in all of them. All patients with ACS
      not provided by epidural anesthesia died. We conclude that conservative therapy
      is effective in IAH, but not in ACS cases. Epidural anesthesia is an effective
      method to treat ACS and should be used in all patients with ACS without sepsis.

PMID- 21957620
TI  - [Using ASV mode for respiratory support withdrawal in patients after posterior
      fossa surgery].
AB  - The study gives data on how to improve the way from mechanical to spontaneous
      breathing in patients with weakened respiratory drive after posterior fossa tumor
      removal. We compared the effectiveness of two methods of weaning from mechanical
      ventilation in these patients. The main group consisted of 6 patients weaned from
      ventilator with ASV mode. The control group was made up of 10 patients weaned
      from ventilator with SIMV or PS modes. The duration of weaning from ventilator
      using ASV mode was significantly shorter than with SIMV or PS modes. During ASV
      ventilation spontaneous breath rate gradually increased. In all patients the
      level of P0,1 index representing respiratory center activity was initially lower
      than normal. While spontaneous breath activity increased the level of P0,1 index
      also gradually normalized. Plmax index (respiratory effort index) measured once a
      day increased as well. Weakened respiratory drive is accompanied by P0,1 and
      Plmax indexes' decrease in patients after posterior fossa tumor removal. ASV mode
      in these patients allows quicker weaning from mechanical ventilation.

PMID- 21957621
TI  - [First experience of using adaptive support ventilation (ASV) mode in patients
      with severe traumatic brain injury].
AB  - Capabilities and limitations of ASV mode in TBI patients are studied. 12 patients
      with severe TBI were enrolled in the study. ICP, MAP, CPP were monitored in all
      the patients. Cerebral regional blood flow was monitored by thermal diffusion in
      four patients. Hamilton G5 ventilator was used for mechanical ventilation and
      respiratory monitoring in all cases. Starting mode of mechanical ventilation was
      ASV with 100% mechanical substitution. The patient was regarded as ASV
      nonresponder and switched to another mode when normoventilation was not possible
      with any percent of respiratory substitution. ASV mode provided normoventilation
      during all period of mechanical ventilation in 88 ou of 12 patients. In 4 out of
      12 patients ASV mode led to hyperventilation with EtC02 decrease, cerebral
      regional blood flow slowing and P0,1 index increase. In three patients
      hyperventilation was induced by high rate of spontaneous breaths caused by
      brainstem irritation. Switching these patients to SIMV-VC led to
      normoventilation, normalization of etC02 and cerebral regional blood flow, and
      P0,1 index decrease. In one patient hyperventilation was caused by lung mechanics
      disorder when ventilator tried to achieve target minute volume by low tidal
      volume and high respiratory rate. ASV mode provides adequate lung ventilation
      during respiratory support period in most patients with severe TBI. It can prove
      ineffective for some patients with brainstem irritation or lung mechanics
      disorders.

PMID- 21957622
TI  - [Intracranial pressure and jugular venous oxygenation influence on outcome in
      patients with severe traumatic brain injury].
AB  - Different criteria are used to predict outcome of TBI including jugular venous
      oxygenation (SjvO2) and ICP. However, there is no data on their combined use. ICP
      measure by ophtalmodynamometry (ODM) of central retinal vein (CR V) never was
      used for outcome prediction. The aim of the study is to assess the effectiveness
      of combined use of ICP and SjvO2 measures for outcome prediction in patients with
      severe TBI. 80 cases of severe TBI with GCS score 8 and lower were studied. In
      addition to the standard monitoring and intensive therapy SjvO2 and ICP by ODM
      during acute period of TBI were measured. Positive outcome of acute TBI can be
      predicted if SjvO2 rate ranges from 55% to 75%. Poor outcome can be predicted if
      SjvO2 rate is lower than 55%. Patients with normal ICP in this group died from
      secondary intracranial complications and patients with high ICP died from primary
      and secondary intracranial injury. Patients with high SjvO2 ( > 75%) also have
      poor prognostic outcome. The main risks for them are extracerebral complications.
      It is necessary to use complex monitoring that includes ICP and SjvO2 for
      accurate prediction of the outcome of TBI. ICP should be measured by minimally
      invasive method.

PMID- 21957623
TI  - [Hyperbaric oxygenation influence on intracranial pressure in patents with
      intracranial hemorrhage receiving mechanical ventilation].
AB  - The study focuses on hyperbaric oxygenation (HBO) influence on the intracranial
      pressure (ICP) in patients with intracranial hemorrhages. Forty eight hyperbaric
      oxygenation sessions in 21 mechanically ventilated patients with intracranial
      hemorrhages were analyzed. HBO was accompanied by ICP increase in 31,3% of cases.
      ICP was stable during 54,2% of sessions and decreased during 14,5% of sessions.
      We didn 't find any relation between ICP dynamics and PaCO2. ICP increase
      correlated with mean BP dynamics which growth by 11% and more was an indicator of
      intracranial hypertension.

PMID- 21957624
TI  - [Analysis of structure of concomitant traumatic brain injury based on multi-field
      hospital data].
AB  - The structure and the circumstances of injury were studied in patients with
      severe TBI. 110 cases were studied retrospectively. More than 70% of the patients
      were from 20 to 60 years old, most of them men (80,91%). The main cause of injury
      was road accident (59,09%). 56,36% of patients were taken to hospital within the
      first hour after the accident. The average score by Glasgow scale was 8 (6;12).
      Lowest scores were registered in patients after railroad accidents [7,5(5;10)],
      in pedestrians [8(5;12)] and passengers [9 (6;12)] after road accidents and in
      criminal trauma cases [9,5(8;11)]. The most severe injuries by PTS scale were
      registered in patients after railroad accidents [50(44;56)], in criminal trauma
      cases [39(36;41)] and in pedestrians [31(22;42)]. The injuries were often
      accompanied by subarachnoid hemorrhage (46,36%). The most often outcome among
      patients with intracerebral hematoma, intraventricular hemorrhage, chest and
      pelvis injury was death. Thus we carried out retrospective analysis and studied
      the structure and the circumstances of TBI in Rostov on Don.

PMID- 21957625
TI  - [Using of tranexamic acid (Tranexam) for prevention and correction of
      coagulopathy during brain tumors removal].
AB  - The aim of the study is to estimate clinical effectiveness of fibrinolysis
      inhibitor Tranexam in neurosurgical patients with intracranial tumors. The
      medication was prescribed to 78 patients from 27 to 65 years old. The control
      group consisted of 57 patients. The following criteria were assessed to estimate
      the impact of the medication on hemostasis: APPT, PT index, TT, fibrinogen, ATIII
      activity, factor XII-derived fibrinolysis, spontaneous euglobulin lysis. Blood
      sampling was drawn at the following stages: after the induction of anesthesia,
      before Tranexam injection, 30 minutes after Tranexam injection, on the next day
      after the surgery. Blood from jugular and peripheral veins was analyzed
      simultaneously. The medication caused significant decrease of fibrinolytic
      activity. The use of Tranexam was followed by bleeding reduction in the wound.
      The duration of surgical hemostasis in the main group was 11,7 +/- 3,3 minutes
      which is significantly lower than in the control group (18,1 +/- 3,1 minutes) (p
      = 0,034). Drainage blood loss was lower in the main group (267 +/- 23 ml a day)
      than in the control group (340 +/- 28 ml a day). Medication injection during
      diffuse bleeding from small vessels led to quick and visible bleeding reduction.
      Thus Tranexam decreases the risk of intraoperative blood loss in the patients
      with brain tumors.

PMID- 21957626
TI  - [Sepsis in patients with intracranial hemorrhage: incidence and influence on
      outcome].
AB  - The aim of the study is to analyze sepsis and septic shock incidence and their
      influence on the outcome in critically ill patients with intracranial hemorrhage.
      Sepsis incidence (33,7%) and septic shock incidence (18,6%) in the patients
      studied did not depend on intracranial hemorrhage etiology. Septic complications
      led to higher mortality which was 22,8% in patients with sepsis and 74,4% in
      patients with septic shock. Sepsis and septic shock risk factors are defined. The
      problem of sepsis and septic shock diagnosis in critically ill patients with
      intracranial hemorrhage are highlighted.

PMID- 21957627
TI  - [Septic encephalopathy: theoretic provocation and clinical illustration].

PMID- 21957628
TI  - [Monitoring of intracranial pressure difference between supra- and infratentorial
      spaces after posterior fossa tumor removal (case report)].
AB  - A clinical example shows that after a neurosurgical operation in posterior fossa
      there could appear intracranial pressure difference between supra- and
      infratentorial spaces. This difference develops due to pressure rise in posterior
      fossa and maintenance of this hypertension postoperatively. Hypertension in
      posterior fossa and intracranial difference are accompanied by brainstem
      reactions and temporary neurological disorders. While the pressure difference
      decreases and ICP in posterior fossa normalizes the neurological symptoms
      disappear. ICP in supratentorial space not necessarily correlates with ICP in
      infratentorial space. In some cases it is necessary to measure ICP in
      infratentorial space after posterior fossa surgery.

PMID- 21957629
TI  - [Bright prospects and deplorable state of prolonged home mechanical ventilation
      in Russia: two cases' description].
AB  - The report describes two patients with lateral amyotrophic sclerosis complicated
      by respiratory insufficiency. Instead of long-term hospitalization to ICU the
      patients were kept at home, where prolonged mechanical ventilation was applied to
      them: in the first case - through tracheostomy tube, in the second - through
      mask. The use of prolonged home mechanical ventilation therapy instead of long
      term hospitalization to ICU is discussed.

PMID- 21957630
TI  - [Trouble in deciduous teeth].

PMID- 21957631
TI  - [New classification system for dental wear].

PMID- 21957632
TI  - [Rotten child dentition].

PMID- 21957633
TI  - [Rather a tooth extraction and an implant than a endodontic treatment. Yes].

PMID- 21957634
TI  - [Rather a tooth extraction and an implant than a endodontic treatment. No].

PMID- 21957635
TI  - [Keratoacanthoma].

PMID- 21957636
TI  - [Herpes simplex].

PMID- 21957637
TI  - [Surprising white lesions].
AB  - A 46-year-old man appeared with white lesions of the oral cavity. A previously
      taken biopsy revealed no classifying diagnosis and treatment with mouth rinse
      produced no improvement. A new biopsy was taken, on which the pathologist
      performed additional tests. This resulted in the diagnosis 'syphilis'. The
      patient was treated with benzylpenicillin and the oral white lesions disappeared.
      Although nowadays syphilis is rare, special attention is required when noticing
      these kinds of lesions of the oral cavity.

PMID- 21957638
TI  - [Synovial chondromatosis of the temporomandibular joint. A systematic review of
      the literature on its characteristics].
AB  - Synovial chondromatosis of the temporomandibular joint is a disease which occurs
      rarely. A systematic review of the literature was carried out to identify its
      demographical, etiological, radiological, and clinical characteristics. A total
      of 191 case presentations were discovered. The mean age of patients was 47. The
      disease has been identified more frequently in women than in men. A part from pre
      auricular swelling, the most frequently reported clinical characteristics
      resembled those of temporomandibular disorders. Abnormalities on radiographs were
      often evident. Insufficient evidence was found that trauma or rheumatoid
      arthritis plays a role in the development of this disease. Given the similarities
      with temporomandibular disorders, synovial chondromatosis should be considered in
      the differential diagnosis of patients suffering from complaints of
      temporomandibular dysfunction.

PMID- 21957639
TI  - [Complications in patients with oral implants. Recommendations for routine
      preventive inspections].
AB  - Oral implantology is a very fast growing and dynamic area of oral healthcare,
      carried out by an increasing number of oral healthcare providers. Recommendations
      for routine preventive inspections are needed to control and monitor the quality
      of treatment. Routine preventive inspection can be divided into inspection of the
      peri-implant hard and soft tissues and inspection of the prosthetic construction.
      The most frequently occurring complications, each with its own treatment, are
      peri-implant mucositis, peri-implantitis, recession of peri-implant tissues, the
      loosening or fracturing of overdenture attachment components, deterioration of
      the fit of overdentures, and the loosening of the screw with which a crown is
      secured on an implant or implant abutment. Carrying out routine preventive
      inspections will make it possible to detect and treat complications in a timely
      fashion.

PMID- 21957640
TI  - [Dissertations 25 years after date 28. Degenerative diseases of the
      temporomandibular joint].
AB  - In 1985, the dissertation 'Temporomandibular joint. Articular cartilage structure
      and function' was published. Much was known at the time concerning the (clinical)
      pathogenesis of osteoarthrosis of the temporomandibuIar joint, the associated
      radiographical characteristics and the results of non-surgical treatment. Little
      was known, however, concerning the processes that lead to the loss of bone tissue
      and other degenerative changes. The current idea that osteoarthrosis was
      histopathologically characterized by defects in the joint surfaces did not seem
      to apply to temporomandibular joints. In temporomandibular joints, the phenomenon
      was recognized of degenerative changes in the deeper layers of the articular
      cartilage and the subchondral bone, while the articular surface could be
      microscopically intact. A dislocated articular disc was seen as part of the
      disease osteoarthrosis. Clear insight into the origins of osteoarthrosis was not
      achieved.

PMID- 21957641
TI  - Biological and cultural markers of environmental pressure.

PMID- 21957642
TI  - !Kung nutritional status and the original "affluent society"--a new analysis.
AB  - The theme of the 2011 meetings of the German Anthropological Society, "Biological
      and Cultural Markers of Environmental Pressure", provides the entree to revisit
      one of Anthropology's most enduring canons - hunters and gathers are well
      nourished and healthy. The Dobe !Kung foragers of the Kalahari Desert often serve
      as a model of hunter-gatherer adaptation for both extant and Paleolithic humans.
      A re-analysis of food intake, energy expenditure, and demographic data collected
      in the 1960s for the Dobe !Kung finds that their biocultural indicators of
      nutritional status and health were, at best, precarious and, at worst, indicative
      of a society in danger of extinction. Hunting and gathering is the lifestyle to
      which the human species was most persistently adapted, in terms of the
      biological, cultural, and emotional meanings of the word 'adapted.' However, the
      few remaining foraging groups studied in the 20th Century are unlikely to serve
      as the ideal models of that ancient way of life.

PMID- 21957643
TI  - Secular trends in some Russian populations.
AB  - Secular changes of body measurements in children have been the subject of studies
      in many different countries. In recent years, there has been an increase in BMI
      associated with a significant trend towards obesity in both Europe and the US.
      The aim of the present study was to analyze trends in body measurements and BMI
      in Russia from the 1960's to the beginning of the 21st century. This was done at
      three locations of the Russian Federation: the city of Moscow, the cities of
      Saratov and Naberezhnye Chelny in the Volga-river area. In addition, data on
      secular changes of Abkhazian children were analyzed. A large number of
      anthropometric measurements were taken on each individual including height,
      weight, arm, leg and trunk lengths (estimated), body diameters and
      circumferences, skinfold thickness, head and face dimensions. Stages of secondary
      sex characteristics also were evaluated; data on menarcheal age were collected by
      status-quo and retrospective methods. Changes in hand grip strength have been
      evaluated in some of the samples. While stature was increasing during these
      years, weight, chest circumference and BMI were characterized by negative
      changes, which became more obvious in elder girls. Changes in handgrip strength
      also showed negative trends. There were noticeable changes in head and face
      measurements, which were expressed in more elongated head and face forms, i.e.
      the head became longer and narrower with narrower and higher faces. Secular
      changes in head and facial morphology may be considered part of the general
      trend.

PMID- 21957644
TI  - Neanderthals: fossil evidence and DNA.
AB  - Neanderthals inhabited Western Eurasia from approximately 300 to 30 thousand
      years ago (ka). They are distinguished by a unique combination of anatomical
      traits, and are commonly associated with Middle Paleolithic lithic industries.
      Current consensus among paleoanthropologists is that they represented a separate
      Eurasian human lineage, which evolved in isolation from the rest of the Old World
      and which shared a common ancestor with modern humans in the Middle Pleistocene.
      It is thought that some aspects of the distinctive Neanderthal anatomy evolved in
      response to selection related to the extreme cold of the European glacial cycles.
      Nevertheless, genetic drift seems to be partially responsible for the evolution
      of these traits. The last appearance of Neanderthals in the fossil record ca. 30
      ka BP dates a few millennia after the first appearance of modern humans in
      Europe. The retrieval of ancient mitochondrial and, more recently, nuclear DNA
      from Neanderthal fossil puts us in the unique position to combine fossil with
      genetic evidence to address questions about their evolution, paleobiology and
      eventual fate.

PMID- 21957645
TI  - Im Osten etwas Neues: Anthropological analysis of remains of German soldiers from
      1915-1918.
AB  - In the summer of 2005, exhumation and identification of the remains of German
      soldiers was performed in Panevezys (Northern Lithuania). Historical data
      indicate that in autumn of 1915 the building of a local gymnasium was transformed
      into a military hospital, and casualties were buried in its garden. The hospital
      functioned until the German withdrawal in the winter 1918. Archaeological finds
      include ID tags, personal items, residues of uniforms and medical devices.
      Routine anthropological analysis was performed on the site, as the remains had to
      be ready for scheduled reburial the same summer. In total, the remains of 837
      soldiers have been discovered. Most of the remains belong to males up to 30 years
      of age. There were, however, remains of five females. The average stature (acc.
      Trotter-Gleser) of males (+/- SD) was 171.4 +/- 5.1 cm (range 155.4-188.8 cm).
      Dental status was characterized by a high incidence of antemortal tooth loss
      (81.8% of individuals, 14.9% teeth) and caries complications. Some healed trauma
      and other lesions (including some suggestive of tuberculosis) indicate that they
      were not obstacles for military service. The highest number of pathologies
      observed was leg trauma (125 cases, among them 49 amputations), followed by head
      trauma (48 cases, among them 13 cases with surgical treatment, and 8 cases of
      maxillofacial lesions), trauma of upper extremity (29 cases, including 9
      amputations); incidence of other kinds of trauma was much lower (trunk area - 7,
      pelvic area - 5, possible abdominal traumas, indicated by metal plates with wire,
      probably used to support drain inserted into abdominal cavity - 36, lesions of
      vertebral column - 2) - this can be explained by worse field-survival after such
      lesions and smaller involvement of the skeleton. However, a significant number of
      skeletons (115) were covered with lime, suggesting death from other (infection?)
      causes; the presence of chronic disease treatment is suggested by a certain
      number (32) of osteoperiosteal lesions. The presence of dissected bodies (13
      cases) indicate systemic analysis of mortality causes. Numerous other pathologies
      and traces of medical interventions are also informative. All this indicates the
      functioning of a large hospital with qualified staff and at least several
      specialised departments.

PMID- 21957646
TI  - Conflict and death in a late prehistoric community in the American Midwest.
AB  - Over the past two decades, it has been recognized that the effects of intergroup
      conflict in prehistoric small-scale societies were greater than previously
      thought. Osteological evidence provides otherwise unobtainable information on the
      number of people who were killed, and who was most likely to become a casualty.
      One such site is Norris Farms #36 in the American Midwest, dating to ca. AD 1300.
      Skeletal evidence of injuries (blunt force trauma and arrow wounds), body
      mutilation (scalping, decapitation, and dismemberment), and scavenger damage
      indicate that one-third of the adults died in a series of ambushes, although
      children were mostly spared. Both young and old adults were killed, and the age
      distributions of the male and female victims were similar. Individuals with
      disabilities that interfered with mobility were more likely to be killed than
      their healthier counterparts. This level of conflict-related mortality almost
      certainly had an effect on the community's ability to conduct its affairs and,
      indeed, to survive as a viable economic and social group.

PMID- 21957647
TI  - Global prevalence of overweight and obesity in preschoolers.
AB  - Twenty-three studies reporting cross-sectional and longitudinal data were
      conducted in 14 different countries between 1998 and 2008. The number of
      preschool age children totaled more than 43,837 with one study not reporting a
      sample size. Studies used both international (i.e., International Obesity Task
      Force (IOTF), World Health Organization (WHO)) and national reference standards
      (i.e., United States - Centers for Disease Control and Prevention (CDC), Spain -
      SRS, Italy - Luciano) to classify children as overweight or obese. Within the
      same sample the percentage of children classified in these categories often
      showed a 1.5- to 2-fold difference in the prevalence of overweight/obesity with
      greatest differences in the between country-specific standards (CDC vs. Luciano).
      WHO percentages frequently exceeded the IOTF percentages. The prevalence of
      overweight/obese children escalated with increasing age from 2-5 years in both
      boys and girls with girls showing higher frequencies in 2/3rds of the 72 sex
      paired comparisons. The results indicate a recent high prevalence of overweight
      and obesity in middle and high income countries, among both well-off and lower
      income segments of populations, in both rural and urban areas, and among all
      ethnic and racial groups represented. Because a high proportion of preschool
      overweight/ obese children will continue to increase their adiposity and are at
      risk for the early onset of metabolic syndrome, cardiovascular disease, type 2
      diabetes, musculoskeletal disorders and behavioral problems, concerted public
      health efforts are needed to coordinate culturally-appropriate parental and
      caregiver education, home lifestyle changes, dietary and exercise modifications
      that will reverse the current trajectory.

PMID- 21957648
TI  - Human development and cultural transmission.
AB  - Transmission of cultural knowledge to children takes several forms. This paper
      argues that there are three basic forms of cultural transmission, which are
      introduced sequentially at different stages of development. Earlier forms are
      retained as new ones are added, and all three forms are used in adult cultural
      transmissions. The introduction of new forms is made possible by the cognitive
      and behavioral consequences of neurological and hormonal changes in the
      developing body.

PMID- 21957649
TI  - Body size of newborns in relation to mother's ethnicity and education: a pilot
      study from Vilnius City (Lithuania), 2005-2010.
AB  - The purpose of this study was to analyse body size indices of newborns in Vilnius
      city (Lithuania) during 2005-2010 in relation with mother's education and
      ethnicity, and in parallel with the changes of socio-economic situation during
      the recent years. The present results were based on data (N = 18,084) from the
      Vilnius University Clinic of Obstetrics and Gynaecology. Comparison of the
      present Lithuanian data with other newborn studies was made. The analysis of
      socio-economic and demographic indicators of Lithuania, and the comparison of
      Gross Domestic Product of various countries was performed. The comparison of body
      size of newborns' data from the different countries showed that Lithuanian
      newborns were among the biggest babies. Some statistically significant
      differences in body size of newborns from different ethnic groups were
      established. Body length of Lithuanian newborns (M = 52.6 cm, SD = 2.5) was
      higher than length of Russian, Ukrainian and Romanian newborns. Body weight of
      Lithuanian newborns (M = 3511 g, SD = 485) was bigger than birth weight of
      Russian, Polish, Ukrainian and Romanian newborns. The analysis of newborns size
      by mother's education showed that body weight of neonates from mothers with the
      university education and from each other education group was bigger in comparison
      with the babies from respectively lower education group. The comparison of
      newborns weight by mother's ethnicity in relation to education level revealed
      nearly no discrepancies between size of newborns from mothers with the same
      education level at different ethnic group. The analysis of birth parameters by
      year has not established a statistically significant difference between the mean
      values for the body weight and body length of the whole investigated contingent
      of the full-term, single-birth newborns from Vilnius city during the 2005-2010.
      However, the tendency has been revealed that newborns from mothers with lower
      education were the most susceptible to negative economic changes after the 2008.

PMID- 21957650
TI  - Most important least respected. Everything you need to know about breakfast.

PMID- 21957651
TI  - The problem of pounds. The parallel paths of obesity and type 2 diabetes.

PMID- 21957652
TI  - Pushing for a cure. What will it really take to end diabetes?

PMID- 21957653
TI  - A dose of tlc.

PMID- 21957654
TI  - The American Idol star talks about her new album amd life with diabetes.
      Interviewed by Tracey Neithercott.

PMID- 21957655
TI  - Smart snacking.

PMID- 21957656
TI  - Are we doing enough to serve our members?

PMID- 21957657
TI  - Opting for Christian Science vs. surgical removal: a case report of a giant basal
      cell carcinoma arising on the back of a 66-year-old man.
AB  - Basal cell carcinoma is the most common form of skin cancer, with giant basal
      cell carcinoma comprising only 0.5 percent of all basal cell carcinomas. When a
      basal cell carcinoma is larger than 5 cm, it is designated as a giant basal cell
      carcinoma. Neglect is often a contributing factor to these lesions, and local
      recurrence and metastasis is not uncommon. Presented is a case of a 66-year-old
      man who presented with a chief complaint of increasing shortness of breath and
      fatigue. The patient was found to have a large 15 cm x 12 cm pedunculated tumor
      on his back that had been present for 10 years. The patient had forgone medical
      attention until presenting with a symptomatic anemia due to his belief in
      Christian Science, which relies on prayer and divine healing for the treatment of
      illness. Christian Scientists are allowed to see physicians, but they may present
      with advanced symptoms or disease presentations due to their beliefs.
      Fortunately, a computed tomography (CT) scan revealed that the tumor was confined
      to the skin, and biopsy revealed a basal cell carcinoma. Thus, the patient was
      able to undergo a wide local excision and split thickness skin graft with clear
      surgical margins.

PMID- 21957658
TI  - Medication use in the elderly: challenges and considerations.

PMID- 21957659
TI  - Immunization reporting in hospitals and clinics.

PMID- 21957660
TI  - Kindness in medicine: appeal and promise.

PMID- 21957661
TI  - A strengths based approach to Australian Aboriginal childrearing practices is the
      answer to better outcomes in Aboriginal family and child health.

PMID- 21957662
TI  - Nurses involved in whistleblowing incidents: sequelae for their families.
AB  - Nurses involved in whistleblowing often face economic and emotional retaliation,
      victimization and abuse. Yet for many nurses, one major part of their
      whistleblowing experience is the negative impact it has on their families. This
      paper reports findings from a qualitative study pertaining to the effects of
      whistleblowing on family life from the perspective of the nurses. Using a
      narrative inquiry approach, fourteen nurses were interviewed who were directly
      involved in whistleblowing complaints. Data analysis drew out three themes:
      strained relationships with family members, dislocation of family life, and
      exposing family to public scrutiny. The harm caused to the nurses involved in a
      whistleblowing event is not restricted to one party but to all those involved, as
      the harrowing experience and its consequences are echoed in the family life as
      well. It is important for organizations to seek strategies that will minimize the
      harmful effects on nurses' families during whistleblowing events.

PMID- 21957663
TI  - The dual roles of rural midwives: the potential for role conflict and impact on
      retention.
AB  - Nurses and midwives continue to make up the largest proportion of the health
      workforce. As a result, shortages of nurses and midwives have a significant
      impact on the delivery of effective health care. Shortages of nurses and midwives
      are known to be more pronounced in rural and remote areas where recruitment and
      retention remain problematic. However, rural nurses are often required to be
      multi-skilled, which has led to expectations that nurses who are also midwives,
      are required to work across areas of the hospital to help to address shortages.
      For midwives this issue is even more problematic as they may actually end up
      spending a very small percentage of their working day involved in the delivery of
      maternity care. This workforce strategy has the potential to seriously erode the
      skills of the midwives. Situations such as this are implicated in attrition of
      midwives because of the role stress that results when they are required to work
      in models of care where they experience the constant pull to work between
      departments and across roles. This paper addresses the requirement for midwives
      in some rural facilities to work across roles of general nurse and midwife and
      outlines the issues that arise as a result. In particular, the paper links the
      concepts of Role Theory to the requirement for midwives to work in dual roles and
      the potential for role stress to develop.

PMID- 21957664
TI  - The role of the nurse sedationist.
AB  - AIM AND OBJECTIVES: This paper aims to provide a quality improvement review to
      identify the benefits and level of satisfaction for the role of the nurse
      sedationists. BACKGROUND: Traditionally procedural sedation was only administered
      by an anaesthetist or dentist and it was not until the early 1990s that nurses in
      America commenced administering procedural sedation. A literature review on the
      role of the nurse sedationist undertaken identified no documented evidence of
      such a role in Australia. The role of the nurse sedationist was pursued as a
      strategy to meet the increased demand for anaesthetic services, manage the
      shortage of anaesthetists and address concerns associated with the administration
      of procedural sedation by healthcare workers untrained in this area. METHOD:
      Evaluation of the role of the nurse sedationist was essential to ensure that the
      role met both the needs of the organisation, patients and key stakeholders. Due
      to the variety of stakeholders and associated expectations a variety of
      evaluation methods were used. RESULTS: Results indicate that the introduction of
      the nurse sedationist role has been recognised as value adding through increases
      in patient safety, a more collaborative approach to patient care, improved work
      environments for all staff groups and strengthened multi disciplinary
      relationships. Patients also indicate a very high level of patient satisfaction
      with the service. CONCLUSION: The role of nurse sedationist has been successfully
      introduced in an Australian acute public hospital. The introduction of the role
      has assisted to address an increased demand for anaesthetic services and to
      address patient safety concerns. RELEVANCE TO CLINICAL PRACTICE: Recent years
      have seen an expansion of advanced practice nursing roles throughout Australia.
      This expansion of roles has resulted in an increase in nursing expertise, high
      quality patient outcomes and an improved multidisciplinary approach to
      healthcare. The role of the nurse sedationist has been a result of expansion in
      this area.

PMID- 21957665
TI  - Trends in publication of research papers by Australian-based nurse authors.
AB  - Analysis of Australian nursing research output is becoming more important as
      academic institutions move into implementing quality programs of research output.
      Notable in determining research quality is the publication of research papers in
      journals with a high ranking within the Institute for Scientific Information
      (ISI) or Excellence in Research for Australia (ERA). This paper reports an
      analysis of Australian nurse researcher output in journals highly ranked by the
      ISI and ERA. Research abstracts were analysed for topic, sources of data,
      location of research and methodological paradigm. A total of 530 articles from
      five Australian and from five USA and UK journals were analysed. There was an
      increase in output from the period of prior analyses in 2000. Practice issues are
      the most common topic followed closely by nurse education. While most studies
      used nurses as sources of data there were more studies in which consumers of
      nursing care were the point of inquiry. Both qualitative and quantitative methods
      were utilised. Given the importance of rationalising nursing practice and adding
      new knowledge to evidence based care, it is imperative for the nursing profession
      to disseminate research findings. Failure to do this may result in poor return in
      investment outcomes for the future of nursing in Australia and internationally.

PMID- 21957666
TI  - Mandatory continuing professional education: what is the prognosis?
AB  - Each year registered nurses apply for registration renewal The Nursing and
      Midwifery Board of Australia stipulate all nurses and midwives are expected to
      take responsibility and accountability for participating in continuing
      professional development (CPD) as a declaration that their practice is current,
      safe and competent. The code of professional conduct and Australian Nursing and
      Midwifery Council (ANMC) competencies governing registered nurses and midwives,
      outline the professional and personal responsibility nurses hold in order to
      maintain clinical competence; which may be achieved through continuing nurse
      education and professional development. As the health care industry shifts focus
      to keep up with changes in technology, economics, demographics and culture, the
      nursing profession must respond accordingly. With the implementation of a
      national registration scheme in Australia, this paper provides a review of the
      literature relating to mandatory CPD and how CPD may assist nurses to respond to
      the changing needs of the health care system and its consumers, to ensure the
      best possible health outcomes. Suggestions of possible avenues of research into
      the concept of CPD are also offered.

PMID- 21957667
TI  - Salovum egg yolk containing antisecretory factor as an adjunct therapy in severe
      cholera in adult males: a pilot study.
AB  - Cholera involves stimulation of intestinal secretory process in response to
      cholera toxin leading to profuse watery diarrhoea that might cause death due to
      dehydration unless timely rehydration therapy is initiated. Efforts to identify
      and test potential antisecretory agents are ongoing. Antisecretory factor (AF) is
      a naturally-occurring protein produced in the human secretory organs, including
      the intestine, with antisectory properties demonstrated in animal and human
      models of secretory diarrhoea. Salovum egg yolk powder contains antisecretory
      proteins in a much higher (500 times) concentration than that of normal hen eggs.
      This is achieved by feeding hens with specially-processed cereals, capable of
      inducing antisecretory proteins in the yolk. The aim of the study was to examine
      the effect of Salovum egg yolk powder containing AF in the treatment of adult
      cholera patients. In an open, randomized controlled trial (pilot study), 40 adult
      male patients with severe cholera were studied: 20 received standard treatment
      (oral rehydration solution, antibiotic, and usual hospital diet) plus Salovum egg
      yolk powder (study group) and 20 received standard treatment alone (control
      group). All the patients received tablet doxycycline (300 mg) once immediately
      after randomization. Written informed consent was obtained from each subject
      before enrollment. The main outcome measures were stool weight and duration of
      diarrhoea. The demographic and baseline clinical characteristics of the study
      patients were comparable between the groups. No significant differences were
      found in the mean stool weight, g/kg of body-weight during the first 24 hours
      [study vs control group, mean +/- standard deviation (SD), 218 +/- 119 vs 195 +/-
      136], second 24 hours (mean +/- SD, 23 +/- 39 vs 22 +/- 34), and cumulative up to
      72 hours (mean +/- SD, 245 +/- 152 vs 218 +/- 169). The duration (hours) of
      diarrhoea after admission in the hospital was also similar in both the groups
      (mean +/- SD, 33 +/- 14 vs 32 +/- 10). No adverse effect was observed. Salovum
      egg powder containing AF as an adjunct therapy in the treatment of severe cholera
      could not demonstrate any beneficial effect. Further studies with higher doses of
      Salovum egg yolk powder might be considered in future to establish its
      antisecretory effect.

PMID- 21957668
TI  - Prevalence of antiretroviral drug resistance mutations and HIV-I subtypes among
      newly-diagnosed drug-naive persons visiting a voluntary testing and counselling
      centre in northeastern South Africa.
AB  - Data on antiretroviral drug resistance among drug-naive persons are important in
      developing sentinel and surveillance policies. This study was conducted to
      determine the prevalence of antiretroviral drug resistance mutations among drug
      naive HIV-infected individuals attending a voluntary testing and counselling
      centre at the Mankweng Hospital in northeastern South Africa. In total, 79 drug
      naive HIV-positive individuals were sequentially recruited during February 2008
      December 2008. Drug resistance mutations were determined using the calibrated
      population resistance tool available on the Stanford HIV drug resistance
      database. Viral DNA was obtained from 57 (72%) of the 79 individuals. Reliable
      nucleotide sequences were obtained for 54 reverse transcriptase (RT) and 54
      protease (PR) gene regions from 54 individuals. Overall, five sequences (9.3%)
      harboured drug resistance mutations (95% confidence interval -1.53 to 16.99).
      Four (7.4%) of these were nucleoside RT inhibitor mutations (D67G, D67E, T69D,
      and T215Y), and one (1.9%) was a PR inhibitor mutation (M46I). No major non
      nucleoside RT resistance mutation was detected. Several minor resistance
      mutations and polymorphisms common in subtype C viruses were observed in the PR
      and RT genes. Phlyogenetic analysis of the partial pol sequences showed that 52
      (96%) of the 54 isolates were HIV-1 subtype C. One isolate (08MB08ZA) was HIV-1
      subtype B while another (08MB26ZA) was related to HIV-1 subtype J. HIV-1 subtype
      recombination analysis with REGA assigned the pol sequence to HIV subtype J
      (11_cpx) with a bootstrap value of 75%. The prevalence of drug resistance
      mutations observed in the population studied was relatively higher than
      previously reported from other parts of South Africa. In addition, this is
      apparently the first report of an HIV-1 subtype J-like virus from northeastern
      South Africa.

PMID- 21957669
TI  - A fifteen-year review of lymphomas in a Nigerian tertiary healthcare centre.
AB  - In Africa, epidemiological data on the effect of the HIV epidemic on the
      occurrence of lymphomas are scanty. The 1990s witnessed the alarming rates of
      HIV/AIDS in Nigeria. The prevalence of HIV/AIDS in Nigeria increased from 1.8% in
      1991 to 4.4% in 2005. The aim of this study was to determine whether there have
      been any changes in the frequency and pattern of lymphomas in view of the
      HIV/AIDS epidemic in the country. This is a retrospective study of all lymphoma
      cases diagnosed during 1991-2005. The prevalence of lymphomas declined from 1.4%
      to 0.7% of surgical biopsies during 1991-2005. There was a decline in the
      proportion of high-grade non-Hodgkin lymphoma and Burkitt's lymphoma from 79.1%
      and 45.8% respectively to 21.1% and 13.6% respectively. There is a suggestion
      that the HIV/AIDS epidemic in the country may not have influenced the pattern of
      occurrence of both major histomorphological types of lymphoma in Ibadan.

PMID- 21957670
TI  - Estimating the effect of recurrent infectious diseases on nutritional status:
      sampling frequency, sample-size, and bias.
AB  - There is an ongoing interest in studying the effect of common recurrent
      infections and conditions, such as diarrhoea, respiratory infections, and fever,
      on the nutritional status of children at risk of malnutrition. Epidemiological
      studies exploring this association need to measure infections with sufficient
      accuracy to minimize bias in the effect estimates. A versatile model of common
      recurrent infections was used for exploring how many repeated measurements of
      disease are required to maximize the power and logistical efficiency of studies
      investigating the effect of infectious diseases on malnutrition without
      compromising the validity of the estimates. Depending on the prevalence and
      distribution of disease within a population, 15-30 repeat measurements per child
      over one year should be sufficient to provide unbiased estimates of the
      association between infections and nutritional status. Less-frequent measurements
      lead to a bias in the effect size towards zero, especially if disease is rare. In
      contrast, recall error can lead to exaggerated effect sizes. Recall periods of
      three days or shorter may be preferable compared to longer recall periods. The
      results showed that accurate estimation of the association between recurrent
      infections and nutritional status required closer follow-up of study participants
      than studies using recurrent infections as an outcome measure. The findings of
      the study provide guidance for choosing an appropriate sampling strategy to
      explore this association.

PMID- 21957671
TI  - Application of factor analysis to identify dietary patterns and use of factor
      scores to study their relationship with nutritional status of adult rural
      populations.
AB  - The prevalence of chronic energy deficiency (CED) among one-third of the Indian
      population is attributed to inadequacy of consumption of nutrients. However,
      considering the complexity of diets among Indians, the relationship between a
      particular dietary pattern and the nutritional status of the population has not
      been established so far. A community-based cross-sectional study was undertaken
      to assess estimates, at district level, of diet and nutritional status in Orissa
      State, India. Factor analysis was used for exploring the existence of consumption
      pattern of food and nutrients and their relationship with the nutritional status
      of rural adult population. Data on 2,864 adult men and 3,525 adult women in
      Orissa state revealed that there exists six patterns among food-groups explaining
      59% of the total variation and three patterns among nutrients that explain 73% of
      the total variation among both adult men and women. The discriminant function
      analysis revealed that, overall, 53% of the men were correctly classified as
      either with chronic energy deficiency (CED) or without CED. Similarly, overall,
      54% of the women were correctly classified as either with CED or without CED. The
      sensitivity of the model was 65% for both men and women, and the specificity was
      46% and 41% respectively for men and women. In the case of classification of
      overweight/obesity, the prediction of the model was about 75% among both men and
      women, along with high sensitivity. Using factor analysis, the dietary patterns
      were identified from the food and nutrient intake data. There exists a strong
      relationship between the dietary patterns and the nutritional status of rural
      adults. These results will help identify the community people with CED and help
      planners formulate nutritional interventions accordingly.

PMID- 21957672
TI  - Socioeconomic determinants of nutritional status of children in Lao PDR: effects
      of household and community factors.
AB  - The prevalence of undernutrition among Lao children is among the highest in the
      region. However, the determinants of childhood undernutrition in Laos have not
      been fully analyzed. This paper, using the dataset of the Lao Multiple Indicator
      Cluster Survey 3, which is a nationally-representative sample in Laos,
      investigated the effects of socioeconomic factors at both household and community
      levels on the nutritional status of children. In the estimation, a multilevel
      linear model with random-intercepts was used for estimating the determinants of
      child anthropometric indices. The empirical results revealed that children from
      households in southern Laos and from ethnic minority groups were less-nourished.
      Level of education of parents, attitudes of mothers towards domestic violence,
      assets of household, local health services, and the condition of sanitation and
      water were considered to be important determinants of nutritional status of
      children. The pattern of growth-faltering in children by age was identified.
      Children aged 12-59 months were less-nourished than those aged 0-11 months. The
      empirical results were consistent with the collective household model which
      incorporates a decision-making process within the household. Since there is
      scarce evidence about the predictors of childhood undernutrition in Laos, the
      findings of this study will serve as a benchmark for future research.

PMID- 21957673
TI  - Association between infant- and child-feeding index and nutritional status:
      results from a cross-sectional study among children attending an urban hospital
      in Bangladesh.
AB  - Integration of infant- and child-feeding index (ICFI) addressing the
      multidimensional child-feeding practices into one age-specific summary index is
      gaining importance. This cross-sectional study was aimed at understanding the
      association between the ICFI and the nutritional status of 259 children, aged 6
      23 months, who attended the paediatric outpatient department of the Dhaka Medical
      College Hospital in Bangladesh. The mean length-for-age z-score (LAZ) of children
      aged 12-23 months was significantly (p < 0.05) higher among those who were at the
      upper ICFI tercile compared to those who were at the middle or lower ICFI tercile
      (-2.01 and -3.20 respectively). A significant correlation was found between the
      ICFI and the LAZ (r = 0.24, p = 0.01 and r = 0.29, p = 0.01) in children aged 6-8
      months and 12-23-months. Multivariable analysis, after adjusting for potential
      confounders, also found a significant association between the ICFI and the LAZ
      (beta = 0.13, p = 0.03). The predictive capability of the proposed ICFI on
      nutritional status of children, especially length-for-age, needs to be further
      evaluated prospectively among healthy children in the community.

PMID- 21957674
TI  - Nutritional status of under-five children living in an informal urban settlement
      in Nairobi, Kenya.
AB  - Malnutrition in sub-Saharan Africa contributes to high rates of childhood
      morbidity and mortality. However, little information on the nutritional status of
      children is available from informal settlements. During the period of post
      election violence in Kenya during December 2007-March 2008, food shortages were
      widespread within informal settlements in Nairobi. To investigate whether food
      insecurity due to post-election violence resulted in high prevalence of acute and
      chronic malnutrition in children, a nutritional survey was undertaken among
      children aged 6-59 months within two villages in Kibera, where the Kenya Medical
      Research Institute/Centers for Disease Control and Prevention conducts population
      based surveillance for infectious disease syndromes. During 25 March-4 April
      2008, a structured questionnaire was administered to caregivers of 1,310 children
      identified through surveillance system databases to obtain information on
      household demographics, food availability, and child-feeding practices.
      Anthropometric measurements were recorded on all participating children. Indices
      were reported in z-scores and compared with the World Health Organization (WHO)
      2005 reference population to determine the nutritional status of children. Data
      were analyzed using the Anthro software of WHO and the SAS. Stunting was found in
      47.0% of the children; 11.8% were underweight, and 2.6% were wasted. Severe
      stunting was found in 23.4% of the children; severe underweight in 3.1%, and
      severe wasting in 0.6%. Children aged 36-47 months had the highest prevalence
      (58.0%) of stunting while the highest prevalence (4.1%) of wasting was in
      children aged 6-11 months. Boys were more stunted than girls (p < 0.01), and
      older children were significantly (p < 0.0001) stunted compared to younger
      children. In the third year of life, girls were more likely than boys to be
      wasted (p < 0.01). The high prevalence of chronic malnutrition suggests that
      stunting is a sustained problem within this urban informal settlement, not
      specifically resulting from the relatively brief political crisis. The
      predominance of stunting in older children indicates failure in growth and
      development during the first two years of life. Food programmes in Kenya have
      traditionally focused on rural areas and refugee camps. The findings of the study
      suggest that tackling childhood stunting is a high priority, and there should be
      fostered efforts to ensure that malnutrition-prevention strategies include the
      urban poor.

PMID- 21957675
TI  - Prevalence of and risk factors for stunting among school children and adolescents
      in Abeokuta, southwest Nigeria.
AB  - Stunting adversely affects the physical and mental outcome of children. The
      objectives of the study were to determine the prevalence of and risk factors
      associated with stunting among urban school children and adolescents in Abeokuta,
      Nigeria. Five hundred and seventy children aged 5-19 years were selected using
      the multi-stage random-sampling technique. Stunting was defined as height-for-age
      z-score (HAZ) of < -2 standard deviation (SD) of the National Center for Health
      Statistics reference. Severe stunting was defined as HAZ of < -3 SD. The mean age
      of the children was 12.2 + 3.41 years, and 296 (51.5%) were males. Ninety-nine
      (17.4%) children were stunted. Of the stunted children, 20 (22.2%) were severely
      stunted. Identified risk factors associated with stunting were attendance of
      public schools (p < 0.001), polygamous family setting (p = 0.001), low maternal
      education (p = 0.001), and low social class (p = 0.034). Following multivariate
      analysis with logistic regression, low maternal education (odds ratio = 2.4; 95%
      confidence interval 1.20-4.9; p = 0.015) was the major contributory factor to
      stunting. Encouraging female education may improve healthcare-seeking behaviour
      and the use of health services and ultimately reduce stunting and its
      consequences.

PMID- 21957676
TI  - Skilled care at birth among rural women in Nepal: practice and challenges.
AB  - In Nepal, most births take place at home, and many, particularly in rural areas,
      are not attended by a skilled birth attendant. The main objectives of the study
      were to assess the use of skilled delivery care and barriers to access such care
      in a rural community and to assess health problems during delivery and seeking
      care. This cross-sectional study was carried out in two Village Development
      Committees in Nepal in 2006. In total, 150 women who had a live birth in the 24
      months preceding the survey were interviewed using a structured questionnaire.
      The sample population included married women aged 15-49 years. Forty-six (31%)
      women delivered their babies at hospital, and 104 (69%) delivered at home. The
      cost of delivery at hospital was significantly (p < 0.001) higher than that of a
      delivery at home. Results of univariate analysis showed that women from Brahmin
      Chhetri ethnicity, women with higher education or who were more skilled, whose
      husbands had higher education and more skilled jobs, had first or second
      childbirth, and having adverse previous obstetric history were associated with
      institutional delivery while women with higher education and having an adverse
      history of pregnancy outcome predicted the uptake of skilled delivery care in
      Nepal. The main perceived problems to access skilled delivery care were: distance
      to hospital, lack of transportation, lack of awareness on delivery care, and
      cost. The main reasons for seeking intrapartum care were long labour, retained
      placenta, and excessive bleeding. Only a quarter of women sought care immediately
      after problems occurred. The main reasons seeking care late were: the woman or
      her family not perceiving that there was a serious problem, distance to health
      facility, and lack of transport. The use of skilled birth attendants at delivery
      among rural women in Nepal is very poor. Home delivery by unskilled birth
      attendants is still a common practice among them. Many associated factors
      relating to the use of skilled delivery care that were identified included age,
      education and occupation of women, and education and occupation of husbands.
      Therefore, the availability of skilled delivery care services at the community,
      initiation of a primary health centre with skilled staff for delivery, and
      increasing awareness among women to seek skilled delivery care are the best
      solution.

PMID- 21957677
TI  - Influences on healthcare-seeking during final illnesses of infants in under
      resourced South African settings.
AB  - To examine how health caregivers in under-resourced South African settings select
      from among the healthcare alternatives available to them during the final illness
      of their infants. Qualitative interviews were conducted with 39 caregivers of
      deceased infants in a rural community and an urban township. Nineteen local
      health providers and community leaders were also interviewed to ascertain
      opinions about local healthcare and other factors impacting healthcare-seeking
      choices. The framework analysis method guided qualitative analysis of data.
      Limited autonomy of caregivers in decision-making, lack of awareness of infant
      danger-signs, and identification of an externalizing cause of illness were
      important influences on healthcare-seeking during illnesses of infants in these
      settings. Health system factors relating to the performance of health workers and
      the accessibility and availability of services also influenced healthcare-seeking
      decisions. Although South African public-health services are free, the findings
      showed that poor families faced other financial constraints that impacted their
      access to healthcare. Often there was not one factor but a combination of factors
      occurring either concurrently or sequentially that determined whether, when, and
      from where outside healthcare was sought during final illnesses of infants. In
      addition to reducing health system barriers to healthcare, initiatives to improve
      timely and appropriate healthcare-seeking for sick infants must take into
      consideration ways to mitigate contextual problems, such as limited autonomy of
      caregivers in decision-making, and reconcile local explanatory models of
      childhood illnesses that may not encourage healthcare-seeking at allopathic
      services.

PMID- 21957678
TI  - Multiple indicator cluster survey 2003 in Afghanistan: outdated sampling frame
      and the effect of sampling weights on estimates of maternal and child health
      coverage.
AB  - Due to an urgent need for information on the coverage of health service for women
      and children after the fall of Taliban regime in Afghanistan, a multiple
      indicator cluster survey (MICS) was conducted in 2003 using the outdated 1979
      census as the sampling frame. When 2004 pre-census data became available,
      population-sampling weights were generated based on the survey-sampling scheme.
      Using these weights, the population estimates for seven maternal and child
      healthcare-coverage indicators were generated and compared with the unweighted
      MICS 2003 estimates. The use of sample weights provided unbiased estimates of
      population parameters. Results of the comparison of weighted and unweighted
      estimates showed some wide differences for individual provincial estimates and
      confidence intervals. However, the mean, median and absolute mean of the
      differences between weighted and unweighted estimates and their confidence
      intervals were close to zero for all indicators at the national level. Ranking of
      the five highest and the five lowest provinces on weighted and unweighted
      estimates also yielded similar results. The general consistency of results
      suggests that outdated sampling frames can be appropriate for use in similar
      situations to obtain initial estimates from household surveys to guide policy and
      programming directions. However, the power to detect change from these estimates
      is lower than originally planned, requiring a greater tolerance for error when
      the data are used as a baseline for evaluation. The generalizability of using
      outdated sampling frames in similar settings is qualified by the specific
      characteristics of the MICS 2003-low replacement rate of clusters and zero
      probability of inclusion of clusters created after the 1979 census.

PMID- 21957679
TI  - Measurement of and trends in unintended birth in Bangladesh, 1983-2000.
AB  - Bangladesh has experienced a rapid decline in fertility in the past several
      decades, facilitated by proactive population policies, provision of
      contraceptives, and broader societal shifts, encouraging smaller families and use
      of contraceptive to achieve revised childbearing norms. This paper presents 18
      years of data from the Sample Registration System, a demographic surveillance
      system operated by the Maternal and Child Health-Family Planning Extension
      Project in six study areas in Bangladesh. Prospective measurements of women's
      fertility preferences were used for classifying nearly 25,000 birth outcomes from
      1983 to 2000 as intended, unintended, or 'up to God/Allah'. Over the 18-year
      period, the level of unintended births varied from 22% to 38%, with the lowest
      levels in the mid-1990s. Fatalistic responses declined significantly from 25% in
      the mid-1980s to 1% by the late 1990s. Results of the comparison of two
      geographic areas of Bangladesh indicate differential declines in the levels of
      unintended pregnancies over the study period. Prospective measurements of
      unintended pregnancies were 2-3 times the magnitude indicated by retrospective
      estimates of unwanted births from the demographic and health surveys conducted
      during the study period. This unique dataset provides a rare opportunity to
      visualize the vast changes in fertility preferences and unintended births in
      Bangladesh from 1983 to 2000. Significant declines in fatalistic responses
      reflect broader social changes that occurred in Bangladesh to facilitate the
      fertility decline and contraceptive uptake. The drastic differences between
      prospective and retrospective measurements of fertility preferences highlight the
      importance of considering the strengths and limitations of each method when
      attempting to estimate the true level of unintended pregnancies and births in a
      population.

PMID- 21957680
TI  - Prevalence and patterns of multimorbidity among elderly people in rural
      Bangladesh: a cross-sectional study.
AB  - Data on multimorbidity among the elderly people in Bangladesh are lacking. This
      paper reports the prevalence and distribution patterns of multimorbidity among
      the elderly people in rural Bangladesh. This cross-sectional study was conducted
      among persons aged > or = 60 years in Matlab, Bangladesh. Information on their
      demographics and literacy was collected through interview in the home.
      Information about their assets was obtained from a surveillance database.
      Physicians conducted clinical examinations at a local health centre. Two
      physicians diagnosed medical conditions, and two senior geriatricians then
      evaluated the same separately. Multimorbidity was defined as suffering from two
      or more of nine chronic medical conditions, such as arthritis, stroke, obesity,
      signs of thyroid hypofunction, obstructive pulmonary symptoms, symptoms of heart
      failure, impaired vision, hearing impairment, and high blood pressure. The
      overall prevalence of multimorbidity among the study population was 53.8%, and it
      was significantly higher among women, illiterates, persons who were single, and
      persons in the non-poorest quintile. In multivariable logistic regression
      analyses, female sex and belonging to the non-poorest quintile were independently
      associated with an increased odds ratio of multimorbidity. The results suggest
      that the prevalence of multimorbidity is high among the elderly people in rural
      Bangladesh. Women and the non-poorest group of the elderly people are more likely
      than men and the poorest people to be affected by multimorbidity. The study sheds
      new light on the need of primary care for the elderly people with multimorbidity
      in rural Bangladesh.

PMID- 21957681
TI  - Microbial contamination of seven major weaning foods in Nigeria.
AB  - Five million children aged less than five years die annually due to diarrhoea.
      The aim of the study was to identify some possible contributing factors for
      persistent diarrhoea. Seven weaning foods, including a locally-made food, were
      evaluated by estimating the microbial load using the most probable number method
      and aflatoxin levels (AFM1, AFG1, AFG2, and AFB2) by immunoaffinity column
      extraction and high-performance liquid chromatography (HPLC) with detection of
      fluorescence. The results showed that the locally-made weaning food had the
      highest microbial count (2,000 cfu/g) and faecal streptococcal count (25 cfu/g).
      Moulds isolated were mainly Aspergillus niger, A. flavus, A. glaucus,
      Cladosporium sp., and Penicillium sp. The home-made weaning food recorded the
      highest fungal count (6,500 cfu/g). AFM1 of the weaning foods was 4.6-530 ng/mL.
      One weaning food had AFB1 level of 4,806 ng/g. Aflatoxin metabolites, apart from
      AFM1 and AFB1 present in the weaning foods, were AFG1 and AFG2. There were low
      microbial counts in commercial weaning foods but had high levels of aflatoxins
      (AFM1, AFG1, AFG2, AFB1, and AFB2). Growth and development of the infant is
      rapid, and it is, thus, possible that exposure to aflatoxins in weaning foods
      might have significant health effects.

PMID- 21957682
TI  - Medical litigation across specialties.

PMID- 21957683
TI  - Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity.

PMID- 21957684
TI  - ARDS: survival has improved but is life worth living?

PMID- 21957685
TI  - Admissions and costs to acute hospitals resulting from road traffic crashes, 2005
      2009.
AB  - Road traffic crashes (RTCs) remain a leading cause of death and injury. The aim
      of this study was to explore the use of hospital data as a source of RTC-related
      injury data in Ireland, as current systems are believed to under-estimate the
      burden. Information on inpatient discharges for years 2005-2009, admitted with
      RTC-related injuries were extracted from HIPE. There were 14,861 discharges;
      9,661 (65.0%) were male, with an average age of 33 years. The median length of
      stay was two days. The most common diagnosis was head injury (n = 4,644; 31.2%).
      The average inpatient hospital cost was Euro 6,395 per discharge. 1,498 (10.1%)
      were admitted to intensive care units. This study has identified 3.5 times more
      serious injuries (14,861) than identified in the Road Safety Authority (RSA)
      statistics (4,263) indicating that the extent of road injuries is greater than
      previously estimated. Hospital data could be used annually in conjunction with
      RSA and other data; ideally the data should be linked.

PMID- 21957686
TI  - EEG use in a tertiary referral centre.
AB  - The aim of this study was to retrospectively audit all electroencephalograms
      (EEGs) done over a 2-month period in 2009 by the Neurophysiology Department at
      Cork University Hospital. There were 316 EEGs performed in total, of which
      176/316 (56%) were done within 24 hours of request. Out of 316 EEGs, 208 (66%)
      were considered 'appropriate' by SIGN and NICE guidelines; 79/208 (38%) had
      abnormal EEGs and 28 of these abnormal EEGs had epileptiform features. There were
      108/316 (34%) 'inappropriate' requests for EEG; of these 15/108 (14%) were
      abnormal. Of the 67/316 (21%) patients who had EEGs requested based on a history
      of syncope/funny turns: none of these patients had epileptiform abnormalities on
      their EEGs. Our audit demonstrates that EEGs are inappropriately over-requested
      in our institution in particular for cases with reported 'funny turns' and
      syncope. The yield from EEGs in this cohort of patients was low as would be
      expected.

PMID- 21957687
TI  - Thoraco-amniotic shunting for fetal pleural effusion--a case series.
AB  - Fetal pleural effusion is a rare occurrence, with an incidence of 1 per 10-15,000
      pregnancies. The prognosis is related to the underlying cause and is often poor.
      There is increasing evidence that in utero therapy with thoraco-amniotic shunting
      improves prognosis by allowing lung expansion thereby preventing hydrops and
      pulmonary hypoplasia. This is a review of all cases of fetal pleural effusion
      managed over an eight year period the National Maternity Hospital Dublin. Over
      the nine year period there were 21 cases of fetal pleural effusion giving an
      overall incidence of 1 per 9281 deliveries. Of these, 15 underwent thoraco
      amniotic shunting. There were associated anomalies diagnosed in 5 (33%) of cases.
      The overall survival in our cohort was 53%. The presence of hydrops was a poor
      prognostic factor, with survival in cases with hydrops of 33% (3/9) compared to
      83% (5/6) in those cases without associated hydrops.

PMID- 21957689
TI  - Inappropriate colonoscopic surveillance of hyperplastic polyps.
AB  - Colonoscopic surveillance of hyperplastic polyps alone is controversial and may
      be inappropriate. The colonoscopy surveillance register at a university teaching
      hospital was audited to determine the extent of such hyperplastic polyp
      surveillance. The surveillance endoscopy records were reviewed, those patients
      with hyperplastic polyps were identified, their clinical records were examined
      and contact was made with each patient. Of the 483 patients undergoing
      surveillance for colonic polyps 113 (23%) had hyperplastic polyps alone on last
      colonoscopy. 104 patients remained after exclusion of those under appropriate
      surveillance. 87 of the 104 patients (84%) were successfully contacted. 37
      patients (8%) were under appropriate colonoscopic surveillance for a significant
      family history of colorectal carcinoma. 50 (10%) patients with hyperplastic
      polyps alone and no other clinical indication for colonoscopic surveillance were
      booked for follow up colonoscopy. This represents not only a budgetary but more
      importantly a clinical opportunity cost the removal of which could liberate
      valuable colonoscopy time for more appropriate indications.

PMID- 21957688
TI  - Influenza and pneumococcal vaccination and varicella status in inflammatory
      arthritis patients.
AB  - Patients with inflammatory arthritis are at increased risk of vaccine preventable
      infections. This risk is increased by immunomodulatory therapies. Vaccination for
      influenza and pneumococcal disease reduces the risk. Severe cases of varicella
      infection have occurred in patients on biologic therapies. We sought to identify
      vaccination rates for commonly acquired infections and to ascertain varicella
      immune status in patients with inflammatory arthritis. 100 patients with
      inflammatory arthritis were administered a standardised questionnaire. Data
      collected included age, diagnosis, vaccination history, history of varicella,
      treatment and the presence of other indications for vaccination. 58 patients
      (58%) had not received the influenza vaccine in the past year. Only 19 patients
      (19%) had ever received pneumococcal vaccine. Anti TNF use did not predict
      vaccination (p = .46). An increasing number of co morbid conditions predicted
      both pneumococcal (p < 0.003) and influenza vaccine (p < 0.03) administration.
      Nineteen patients (19%) gave no history of varicella infection, none having had
      varicella titres checked pre treatment. Immunisation rates in patients with
      inflammatory arthritis on immunosuppressive therapies are low. Immunisation
      schedules should be available for each patient during rheumatology and general
      practice consultations.

PMID- 21957690
TI  - Towards the development of integrated epilepsy services: an audit of documented
      epilepsy care.
AB  - Effective chronic disease management (CDM) requires the ready availability and
      communication of accurate, clinical disease specific information. Using epilepsy
      as a probe into CDM, we report on the availability and reliability of clinical
      information in the primary care records of people with epilepsy (PWE). The
      medical records of 374 PWE from 53 general practices in the Mid-West region of
      Ireland were examined. Confirmation of an epilepsy diagnosis by a neurologist was
      documented for 132 (35%) patients. 282 (75%) patients had no documented evidence
      of receiving specialist neurology review while 149 (40%) had not been reviewed by
      their GP in the previous two years for their epilepsy. Significant variation in
      documentation of epilepsy specific information together with an inadequacy and
      inconsistency of existing epilepsy services was highlighted.

PMID- 21957691
TI  - Maternity services for obese women in Ireland.
AB  - Nearly one in five women booking for antenatal care in Ireland is obese. The
      purpose of this survey was to audit the services and facilities for obese
      pregnant women in the country's maternity units. In June 2010, a detailed
      questionnaire was sent to all 20 units which included questions on services,
      equipment and facilities for obese women. All 20 units responded: 17 (85%) were
      calculating and recording Body Mass Index in pregnancy. Only 15 (75%) were
      screening obese women for gestational diabetes mellitus and 2 (10%) were omitting
      thromboprophylaxis for caesarean section in obese women. Only 3 (15%) had
      clinical guidelines for obesity and pregnancy. The facilities and equipment,
      particularly for severely obese women, were inadequate in the majority of units.
      This survey showed variations nationally in obstetric practices and facilities.
      It highlights the need to develop, disseminate and implement standardised
      guidelines on maternal obesity.

PMID- 21957692
TI  - Potential organ donor audit in Ireland: response from the Irish Lung Fibrosis
      Association.

PMID- 21957693
TI  - Successful screening--Breastcheck uptake in urban general practice.

PMID- 21957694
TI  - Infant mortality statistics from the 2007 period linked birth/infant death data
      set.
AB  - OBJECTIVES: This report presents 2007 period infant mortality statistics from the
      linked birth/infant death data set (linked file) by a variety of maternal and
      infant characteristics. The linked file differs from the mortality file, which is
      based entirely on death certificate data. METHODS: Descriptive tabulations of
      data are presented and interpreted. RESULTS: The U.S. infant mortality rate was
      6.75 infant deaths per 1,000 live births in 2007, not significantly different
      than the rate of 6.68 in 2006. Infant mortality rates ranged from 4.57 per 1,000
      live births for mothers of Central and South American origin to 13.31 for non
      Hispanic black mothers. Infant mortality rates were higher for those infants who
      were born in multiple deliveries; for those whose mothers were born in the 50
      states or the District of Columbia; and for mothers who were unmarried. Infant
      mortality was also higher for male infants and infants born preterm or at low
      birthweight. The neonatal mortality rate was essentially unchanged from 2006
      (4.46) to 2007 (4.42). The postneonatal mortality rate increased 5 percent from
      2.22 in 2006 to 2.33 in 2007, similar to the rate in 2005 (2.32). Infants born at
      the lowest gestational ages and birthweights have a large impact on overall U.S.
      infant mortality. For example, more than one-half of all infant deaths in the
      United States in 2007 (54 percent) occurred to the 2 percent of infants born very
      preterm (less than 32 weeks of gestation). Still, infant mortality rates for late
      preterm infants (34-36 weeks of gestation) were 3.6 times, and those for early
      term (37-38 weeks) infants were 1.5 times, those for infants born at 39-41 weeks
      of gestation, the gestational age with the lowest infant mortality rate. The
      three leading causes of infant death--congenital malformations, low birthweight,
      and sudden infant death syndrome--accounted for 45 percent of all infant deaths.
      The percentage of infant deaths that were "preterm-related" was 36.0 percent in
      2007. The preterm-related infant mortality rate for non-Hispanic black mothers
      was 3.4 times higher, and the rate for Puerto Rican mothers was 71 percent higher
      than for non-Hispanic white mothers.

PMID- 21957695
TI  - Descriptive epidemiology of dance participation in adolescents.
AB  - The aims of this study were to describe the prevalence of dance participation in
      U.S. adolescents and to estimate the contribution of dance to total moderate-to
      vigorous physical activity (MVPA). The sample was composed of 3,598 adolescents
      from the 2003-06 National Health and Nutrition Examination Survey. Youth reported
      frequency and duration of physical activities performed in the past month. Dance
      participation prevalence was calculated; among those who reported dance, its
      contribution to total MVPA was estimated. The prevalence of dance was much higher
      in girls (34.8%) than boys (8.4%). Girls had a greater contribution of dance to
      total MVPA (39.3%) than boys (23.0%). Dance is a prevalent form of physical
      activity among girls, and it accounts for a substantial fraction of their total
      MVPA.

PMID- 21957696
TI  - Differential item functioning analysis of the 2003-04 NHANES physical activity
      questionnaire.
AB  - Using differential item functioning (DIF) analyses, this study examined whether
      there were any DF items in the National Health and Nutrition Examination Survey
      (NHANES) physical activity (PA) questionnaire. A subset of adult data from the
      2003-04 NHANES study (n = 3,083) was used. PA items related to respondents'
      occupational, transportation, domestic, leisure-time, strength-related, and
      sedentary activities were analyzed for DIF using Mantel-Haenszel, SIBTEST, and
      analysis of variance procedures. Some items were identified as DF items, with the
      majority of those items favoring advantaged social groups. For example, items
      about domestic activity and moderate-intensity leisure-time activity were DF
      items favoring non-Hispanic Whites, and persons with higher levels of education
      (e.g., some college or more) or income (e.g, annual family income [AFI] >
      $34,999). The vigorous activity item was a DIF item favoring younger adults (ages
      20-59 years) and persons with higher levels of education or income. Occupational
      PA presented DF favoring Hispanics and persons with lower levels of education
      (e.g., high school or less), and the transportation-related PA item presented DF
      favoring persons with lower incomes (e.g., AFI $34,999). These findings highlight
      the importance of conducting DF analysis in PA survey construction and emphasize
      the need to introduce DIF concepts and methods to PA researchers.

PMID- 21957697
TI  - Correction equations to adjust self-reported height and weight for obesity
      estimates among college students.
AB  - The purposes of this study were to generate correction equations for self
      reported height and weight quartiles and to test the accuracy of the body mass
      index (BMI) classification based on corrected self-reported height and weight
      among 739 male and 434 female college students. The BMIqc (from height and weight
      quartile-specific, corrected self-reported measurements) provided a more accurate
      estimation of BMI classification than BMIc (from corrected self-reported
      measurements) and BMIs (from self-reported measurements) by showing a greater
      ability to predict cases with either a high or a low BMI category while still
      maintaining a high specificity. However, the equations are applicable only to
      Caucasian college student populations, so cross-validation in similar populations
      is needed before they are used more broadly.

PMID- 21957698
TI  - A new time measurement method using a high-end global navigation satellite system
      to analyze alpine skiing.
AB  - Accurate time measurement is essential to temporal analysis in sport. This study
      aimed to (a) develop a new method for time computation from surveyed trajectories
      using a high-end global navigation satellite system (GNSS), (b) validate its
      precision by comparing GNSS with photocells, and (c) examine whether gate-to-gate
      times can provide more detailed information about alpine skiing performance. The
      results demonstrated small mean time differences with no systematic bias, with a
      velocity dependent scatter of time differences, which diminished at higher
      velocities. Furthermore, the multiple gate-to-gate and lag times demonstrated
      that the GNSS enabled a more detailed analysis compared to photocells. The
      measurements using GNSS showed high validity and potential as a tool for more
      specific analysis of performance in skiing.

PMID- 21957699
TI  - Sample size and power estimates for a confirmatory factor analytic model in
      exercise and sport: a Monte Carlo approach.
AB  - Monte Carlo methods can be used in data analytic situations (e.g., validity
      studies) to make decisions about sample size and to estimate power. The purpose
      of using Monte Carlo methods in a validity study is to improve the methodological
      approach within a study where the primary focus is on construct validity issues
      and not on advancing statistical theory. The purpose of this study is to
      demonstrate how Monte Carlo methods can be used to determine sample size and to
      estimate power for a confirmatory factor analytic model under model-data
      conditions commonly encountered in exercise and sport. Because the purpose is
      pursued by way of demonstration with the Coaching Efficacy Scale II-High School
      Teams, related sample size recommendations are provided: N > or = 200 for the
      theoretical model; N > or = 300 for the population model. Technical terms (e.g.,
      coverage) are defined when necessary.

PMID- 21957700
TI  - Concurrent validity of the Polar s3 Stride Sensor for measuring walking stride
      velocity.
AB  - With this research, we sought to establish the accuracy of stride velocity data
      collected by the s3 Stride Sensor Participants walked along a GAITRite mat at
      self-selected slow, preferred, and fast velocities, with two s3 Stride Sensors
      attached to their right foot. The start position was systematically varied such
      that the GAITRite system would record the second through sixth strides at each
      walking velocity. Both slow and preferred walking velocities were underestimated
      by 14% relative to the GAITRite (p < .05), while independent of walking velocity,
      Strides 2 and 3 were underestimated by 26% and 9% (p < .05), respectively.
      Researchers should use caution when interpreting data collected at slow and
      preferred walking velocities and during the first three strides.

PMID- 21957701
TI  - Internal and external focus of attention in a novice form sport.
AB  - In the current experiment, we examined optimal focus for novices during a
      movement sequence in which performance was measured on accurate movement
      form/technique. A novel gymnastics routine was practiced under either an internal
      skill-relevant, internal skill-irrelevant, external, or no attention focus.
      Retention and transfer tests were then completed. During acquisition, adopting an
      internal irrelevant focus significantly improved performance, whereas an external
      focus degraded performance. There were no significant group differences in the
      retention and transfer tests. This suggests that learning of movement
      form/technique did not benefit from a specific focus of attention. The results
      are interpreted via an attentional capacity viewpoint and the notion that form
      tasks do not always contain obvious movement effects central to common coding and
      the constrained action hypothesis.

PMID- 21957702
TI  - The relationship between motor skill proficiency and body mass index in preschool
      children.
AB  - The purpose of this study was to examine the relationship between motor
      proficiency and body mass index (B/MI) in preschool children. Thirty-eight
      children ages 4-6 years had their BMI calculated and were assessed using the
      Movement Assessment Battery for Children-2 (MABC-2; Henderson, Sugden, & Barnett,
      2007). These data were analyzed in two ways. The correlation between BMI and MABC
      2 percentile ranks was calculated. Next, the groups were subdivided based on BMI
      status (high, M = 85.5; medium, M = 49.8; low, M = 10.8), and compared using t
      tests to determine if differences existed in MABC-2 percentile ranks. No
      significant relationship existed between MABC-2 and BMI percentile ranks (r = 
      .237). However significant differences in MABC-2 percentile ranks existed between
      high and low (p = .042), and high and medium (p = .043) groups. These results
      suggest that preschool children classified as overweight or obese may have lower
      motor proficiency than their normal weight and under weight peers. This study
      indicates there is a direct relationship between motor proficiency and BMI in the
      preschool population.

PMID- 21957703
TI  - Allowing learners to choose: self-controlled practice schedules for learning
      multiple movement patterns.
AB  - For this study, we investigated the effects of self-controlled practice on
      learning multiple motor skills. Thirty participants were randomly assigned to
      self-control or yoked conditions. Participants learned a three-keystroke pattern
      with three different relative time structures. Those in the self-control group
      chose one of three relative time structures before each of 90 practice trials;
      yoked participants were not allowed to choose but were yoked to a self-control
      participant and followed that individual's sequence of practice trials. Results
      of the 24-hr serial transfer test revealed the self-control group exhibited
      significantly lower relative timing error, absolute error, and total error than
      the yoked group. Findings further support the efficacy of self-controlled
      learning

PMID- 21957704
TI  - Effects of training on the estimation of muscular moment in submaximal exercise.
AB  - The purpose of this study was to observe the effects of a submaximal isometric
      training program on estimation capacity at 25, 50, and 75% of maximal contraction
      in isometric action and at two angular velocities. The second purpose was to
      study the variability of isometric action. To achieve these purposes,
      participants carried out an isokinetic extension movement of the dominant lower
      limb during six test sessions and nine training sessions. Following the training
      program, estimation capacity in the different actions did not improve. However an
      improvement in performance was observed with a reduction in the variability of
      submaximal isometric actions. The proprioceptors activated in isometric action
      seemed to adapt to the training program itself which would promote better
      adaptation by a greater solicitation of internal feedback.

PMID- 21957705
TI  - Instructions to adopt an external focus enhance muscular endurance.
AB  - The influence of internal (movement focus) and external (outcome focus)
      attentional-focusing instructions on muscular endurance were investigated using
      three exercise protocols with experienced exercisers. Twenty-three participants
      completed a maximal repetition, assisted bench-press test on a Smith's machine.
      An external focus of attention resulted in significant (p < .05) improvements in
      performance compared to the internal focus of attention, but not the control
      condition. Seventeen participants completed repetitions to failure at 75% 1-RM on
      free bench press and squat exercises. In both tasks, externally focused
      instructions resulted in significantly greater repetitions to failure than
      control and internal focus conditions (p < .05). These results support previous
      research showing beneficial effects of externally focused instructions on
      movement efficiency.

PMID- 21957706
TI  - Self-controlled amount of practice benefits learning of a motor skill.
AB  - Self-control over factors involving task-related information (e.g, feedback) can
      enhance motor learning. It is unknown if these benefits extend to manipulations
      that do not directly affect such information. The purpose of this study was to
      determine if self-control over the amount of practice would also facilitate
      learning Participants learned to throw a dart using their nonpreferred hand. The
      self-control (SC) group decided when to stop practice. The yoked group completed
      the same number of trials as their SC counterparts. Results revealed the SC group
      was more accurate during transfer and in recalling the number of trials
      completed. These findings indicate that self-control benefits extend to factors
      that do not directly alter task-related information.

PMID- 21957707
TI  - Student teachers' use of instructional choice in physical education.
AB  - Guided by self-determination theory and research on teacher beliefs, we examined
      student teachers' (STs) use of instructional choices in teaching physical
      education classes. Participants included 131 STs (52 men and 79 women) from a
      major university in the United States. STs completed questionnaires assessing
      three types of instructional choices (cognitive, organizational, and procedural)
      they provided and their rationale for providing their students with choices. The
      STs reported they gave students cognitive, organizational, and procedural
      choices. They firmly believed instructional choice promotes students' motivation,
      autonomy, and engagement in physical education. They also believed teachers
      should consider factors such as student characteristics and the beneficial
      effects when implementing choice in their classes.

PMID- 21957708
TI  - Physical activity correlates for children with autism spectrum disorders in
      middle school physical education.
AB  - This study examined potential correlates that might influence physical activity
      (PA) of adolescents with autism spectrum disorders (ASD) in physical education.
      Students with (n = 19) and without (n = 76) ASD wore an accelerometer during
      physical education. Data were collected in 38 physical education lessons. The
      results showed that (a) students with ASD were less physically active than their
      peers, (b) their PA was related positively to their social interaction with
      peers, and (c) their moderate to vigorous PA depended on PA content, physical
      environment, and instructor-related characteristics. The findings suggest a need
      for additional studies on the relationship between the needs of adolescents with
      ASD and the content offered in physical education so as to inform school policies
      and help to remove barriers to promoting PA among this population.

PMID- 21957709
TI  - Implementation fidelity of a program designed to promote personal and social
      responsibility through physical education: a comparative case study.
AB  - The purpose of this qualitative comparative case study was to examine the
      implementation fidelity of a program designed to deliver the Teaching Personal
      and Social Responsibility (TPSR) model (Hellison, 2003) through physical
      education and its relationship with short-term outcomes for elementary school
      students. The research questions were: (a) was the program implemented with
      fidelity, and (b) did better fidelity yield better student outcomes. Thus, we
      conducted a study on the implementation process used by two teachers who
      delivered the same program in two physical education classes in two different
      elementary schools in Spain. Data sources included observations and interviews
      with teachers and nonparticipant observers. Findings indicated that fidelity of
      implementation in Case 1 was higher and most children in those classes acquired
      the first three of five TPSR responsibility levels. Implementation fidelity in
      Case 2 was weaker and achievement of responsibility goals was minimal (only the
      first of five levels) and less stable for those students. This study is the first
      to directly examine the connection between TPSR implementation fidelity and
      student outcomes.

PMID- 21957710
TI  - The influence of physical education on physical activity levels of urban
      elementary students.
AB  - The purpose of this study was to examine the role of physical education in
      shaping physical activity patterns. Seventy-one Hispanic and African American
      elementary students participated in the study. Students attended one 30- and one
      60-min physical education class weekly. Pedometer steps were used to estimate
      physical activity. Data suggest that students did not engage in enough physical
      activity on a daily basis to incur health benefits. There were significant step
      differences in 0-, 30-, and 60-min physical education days, with the most steps
      occurring on 60-min days. Results from the study suggest physical education may
      be an important source of physical activity for Hispanic and African American
      students, especially girls, and may influence participation in physical activity
      outside of class.

PMID- 21957711
TI  - The effects of physical activity and physical fitness on children's achievement
      and cognitive outcomes: a meta-analysis.
AB  - It is common knowledge that physical activity leads to numerous health and
      psychological benefits. However; the relationship between children's physical
      activity and academic achievement has been debated in the literature. Some
      studies have found strong, positive relationships between physical activity and
      cognitive outcomes, while other studies have reported small, negative
      associations. This study was a comprehensive, quantitative synthesis of the
      literature, using a total of 59 studies from 1947 to 2009 for analysis. Results
      indicated a significant and positive effect of physical activity on children's
      achievement and cognitive outcomes, with aerobic exercise having the greatest
      effect. A number of moderator variables were also found to play a significant
      role in this relationship. Findings are discussed in light of improving
      children's academic performance and changing school-based policy.

PMID- 21957712
TI  - Effects of curricular activity on students' situational motivation and physical
      activity levels.
AB  - The purpose of this study was to examine (a) the effects of three curricular
      activities on students'situational motivation (intrinsic motivation [IM],
      identified regulation [IR], external regulation, and amotivation [AM]) and
      physical activity (PA) levels, and (b) the predictive strength of situational
      motivation to PA levels. Four hundred twelve students in grades 7-9 participated
      in three activities (cardiovascular fitness, ultimate football, and Dance Dance
      Revolution [DDR]) in physical education. ActiGraph GT1M accelerometers were used
      to measure students' PA levels for three classes for each activity. Students also
      completed a Situational Motivation Scale (Guay, Vallerand, & Blanchard, 2000) at
      the end of each class. Multivariate analysis of variance revealed that students
      spent significantly higher percentages of time in moderate-to-vigorous PA (MVPA)
      in fitness and football classes than they did in DDR class. Students reported
      higher lM and IR toward fitness than DDR They also scored higher in IR toward
      fitness than football. In contrast, students displayed significantly lower AM
      toward fitness than football and DDR Hierarchical Linear Modeling revealed that
      IM was the only positive predictor for time in MVPA (p = .02), whereas AM was the
      negative predictor (p < .01). The findings are discussed in regard to the
      implications for educational practice.

PMID- 21957713
TI  - Comparison of the validity of four fall-related psychological measures in a
      community-based falls risk screening.
AB  - We examined the measurement properties offall-related psychological instruments
      with a sample of 133 older adults (M age = 74.4 years, SD = 9.4). Measures
      included the Comprehensive Falls Risk Screening Instrument, Falls-efficacy Scale
      International (FES-I), Activities-specific Balance Confidence (ABC), modified
      Survey ofActivities and Fear ofFalling in the Elderly (mSAFFE), Consequences of
      Falling (CoF), Physical Activity Scale for the Elderly (PASE), and 36-Item Short
      Form Health Survey (SF-36). The FES-I, ABC, mSAFFE, and CoF were significantly
      correlated with each othe, with SF-36, and with mobility. The ABC and mSAFFE were
      significantly correlated with PASE. The ABC differentiated between fallers and
      nonfallers and predicted total falls risk. Findings can assist with the selection
      of psychological instruments in a falls risk screening context.

PMID- 21957714
TI  - The functional equivalence between movement imagery, observation, and execution
      influences imagery ability.
AB  - Based on literature identifying movement imagery, observation, and execution to
      elicit similar areas of neural activity, research has demonstrated that movement
      imagery and observation successfully prime movement execution. To investigate
      whether movement and observation could prime ease of imaging from an external
      visual-imagery perspective, an internal visual-imagery perspective, and
      kinesthetic modality, 36 participants (M age = 20.58; SD = 3.11; 18 women and 18
      men) completed an adapted version of the Movement Imagery Questionnaire-Revised
      under four modes of delivery (movement prime, external observation prime,
      internal observation prime, and image-only). The results revealed that ease of
      imaging was significantly greater during the movement and observation prime
      conditions compared to the image-only condition (p < .05). Specifically when
      priming external visual imagery and internal visual imagery, observation
      facilitated ease of imaging only when the perspective was congruent with the
      imagery perspective. The results support the use of movement and observation to
      facilitate ease of imaging, but highlight the importance of considering the
      visual perspective when using observation.

PMID- 21957715
TI  - Objectively assessed physical activity among Tongans in the United States.

PMID- 21957716
TI  - No relative age effect in the birth dates of award-winning athletes in male
      professional team sports.

PMID- 21957717
TI  - The effects of focus of attention and task objective consistency on learning a
      balancing task.

PMID- 21957718
TI  - Effects of continuing professional development on urban elementary students'
      knowledge.
AB  - This study supports the important role teacher training programs can play in
      increasing physical education knowledge. In this project, teachers were able to
      increase students' understanding of critical physical activity/fitness knowledge
      through physical education instruction, without changing the physical education
      contact time. This link to student needs as well as the school's overall mission
      is a promising one for students and schools alike.

PMID- 21957719
TI  - Effect of exercise training on hippocampal volume in humans: a pilot study.

PMID- 21957720
TI  - Introduction to special issue commemorating the 10th anniversary of September 11,
      2001.
AB  - Dr Boscarino was in the World Trade Center complex on September 11, 2001 when the
      first plane struck the Twin Towers. His World Trade Center work was supported in
      part by grants from the National Institute of Mental Health (Grants # R01 MH66403
      and R21-MH-086317) and the Pennsylvania Department of Health (Contract
      #4100042573).

PMID- 21957721
TI  - Perievent panic attack and depression after the World Trade Center disaster: a
      structural equation model analysis.
AB  - Research suggests that perievent panic attacks--panic attacks in temporal
      proximity to traumatic events--are predictive of later mental health status,
      including the onset of depression. Using a community sample of New York City
      residents interviewed 1 year and 2 years after the World Trade Center Disaster,
      we estimated a structural equation model (SEM) using pre-disaster psychological
      status and post-disaster life events, together with psychosocial resources, to
      assess the relationship between perievent panic and later onset depression.
      Bivariate results revealed a significant association between perievent panic and
      both year-1 and year-2 depression. Results for the SEM, however showed that
      perievent panic was predictive of year-1 depression, but not year-2 depression,
      once potential confounders were controlled Year-2 stressors and year-2
      psychosocial resources were the best predictors of year-2 depression onset. Pre
      disaster psychological problems were directly implicated in year-1 depression,
      but not year-2 depression. We conclude that a conceptual model that includes pre-
      and post-disaster variables best explains the complex causal pathways between
      psychological status, stressor exposure, perievent panic attacks, and depression
      onset two years after the World Trade Center attacks.

PMID- 21957722
TI  - Working toward resilience: a retrospective report of actions taken in support of
      a New York school crisis team following 9/11.
AB  - A retrospective report details external support rendered to a Lower Manhattan
      school crisis team following the 9/11/01 terrorist attack on the World Trade
      Center This analysis occasions an opportunity for consideration of working
      assumptions, the formative use of data to plan support actions, and the
      subsequent emergence of a collaborative approach to post-disaster team support in
      school settings. The nature of assessment and nature of subsequent service
      delivery illustrates a community resilience-based approach to school crisis
      management. Recommendations for such work are based upon mixed qualitative and
      quantitative data gathered from on-scene team members as part of the ongoing
      support effort.

PMID- 21957723
TI  - Reflections on ten years of clinical practice in New York City following the
      terrorist attacks of September 11, 2001.

PMID- 21957724
TI  - Psychological interventions for terroristic trauma: prevention, crisis
      management, and clinical treatment strategies.
AB  - Terrorist attacks combine features of a criminal assault, a mass casualty
      disaster and an act of war Accordingly, this article presents a model for
      prevention, response and recovery from the psychological impact of a terror
      attack. The nature of terrorism is delineated and the various psychological
      effects are described, including diagnostic clinical syndromes, as well as
      individual reactions. Interventions in the immediate aftermath of a terrorist
      attack include on-scene crisis intervention, short-term psychological
      stabilization, and longer-term psychotherapeutic approaches. Special techniques
      are described for individuals, families, children, and large groups of survivors
      and responders. Finally, the ways that mental health clinicians can serve as
      valuable consultants to community recovery efforts are discussed.

PMID- 21957725
TI  - Collateral damage in disaster workers.
AB  - Disaster workers are not immune to the negative personal and professional effects
      of their services at a disaster. For the purposes of this article, the intra and
      interpersonal disturbances that arise from disaster work are called "collateral
      damage. " The harmful effects may range from, among other reactions, feelings of
      disappointment, confusion, resentment, anger; and lack of appreciation to the
      more serious reactions such as anxiety attacks, severe social withdrawal,
      substance abuse, and Post Traumatic Stress Disorder This article reviews some of
      the causative factors of personal distress and disruptions to teamwork in
      disaster relief operations. It suggests a variety of practical methods to reduce
      the potential of collateral damage among disaster response personnel.

PMID- 21957726
TI  - Time-dependent changes of cytokines mRNA in bronchoalveolar lavage fluid from
      symptomatic recurrent airway obstruction-affected horses.
AB  - During an 18 day test, we measured the cytokine mRNA expression (Interleukin
      1beta [IL-1beta], Interleukin-8 [IL-8], Interferon-gamma [IFN-gamma], Tumor
      Necrosis Factor-alpha [TNF-alpha]) of cells from bronchoalveolar lavage fluid
      [BALF] in five horses previously diagnosed with RAO, before and during challenge
      exposure, and after the desensitization phase which involved dexamethasone
      treatment and environmental modification. Simultaneously, the same cytokine mRNA
      expression of cells from BALF in four asymptomatic RAO-affected horses maintained
      outdoors was analyzed. An evident respiratory distress was observed in the
      challenge group within 3 days, with a significant overexpression of IL-8 and TNF
      alpha mRNA on the ninth day. The pharmacological and environmental
      desensitization provided a down regulation of all the cytokines. No statistical
      modification characterized the cytokine kinetics of the asymptomatic horses
      maintained outdoors. A comparison for each time point of the cytokines between
      the exposed and unexposed horses showed no significant differences. The study
      suggested that a standardized exposure protocol and sampling time in experimental
      studies of RAO is mandatory for a correct comparison of the results obtained by
      different Authors. However, the absence of significant changes between the
      exposed and unexposed horses could depend on the lack of the sample uniformity
      since the evolution of the disease represents a continuum from a healthy to a
      pathological condition.

PMID- 21957727
TI  - Metabolic and immune response of young turkeys originating from parent flocks fed
      diets with inorganic or organic selenium.
AB  - The aim of this study was to verify the hypothesis that the health and growth of
      turkey poults may be improved by supplementing diets fed to parent flocks with
      available selenium. Experimental poults originated from parent flocks fed with
      diets containing 0.3 mg/kg inorganic selenium (control group Se(M)) and organic
      selenium (experimental group Se(O)). Egg yolk selenium content was comparable in
      both flocks (0.72 and 0.70 mg/kg d.m., respectively). Eggs from the Se(O) flock
      had a significantly lower content of thiobarbituric acid reactive substances -
      TBARS (31.13 vs. 53.10 nmol/g, p > 0.001). Se(O) group poults were characterized
      by higher activity of glutathione peroxidase (7.54 vs. 5.92 U/mL, P = 0.001) and
      superoxide dismutase (89.30 vs. 79.23 U/mL, P = 0.026). The thigh muscles of
      Se(O) group birds had significantly higher selenium concentrations (0.74 vs.
      0.57, p = 0.045) and a significantly lower TBARS content (38.42 vs. 65.01, p =
      0.001). No differences were found between the groups with respect to the content
      of total protein, albumins and uric acid, and the activites of alanine
      aminotransferase (ALT), aspartate aminotransferase (AST) and lactate
      dehydrogenase (DLH) in day-old poults. On day 28, groups Se(O) and Se(M) differed
      in the activity of ALT (20.50 vs. 26.33, p = 0.05) and SOD (87.29 vs. 100.02
      U/mL, p = 0.035). There were no differences between the groups regarding the
      percentages of T lymphocyte subpopulations CD4+, CD8+, CD4+CD8+ and B lymphocyte
      subpopulations (IgM+) at 1 and 28 days of age. Over the experimental period,
      mortality rates were similar in both groups (7.32 and 8.87%), and so were the
      final body weights of birds (1108 vs. 1135 g). The results of the study show that
      the dietary supplementation of organic selenium in turkey parent flocks reduces
      the rate of oxidation processes in the egg and in the tissues of newly-hatched
      poults, yet it has no effect on the analyzed parameters of cell-mediated immunity
      and the growth performance of birds during the first five weeks of their life.

PMID- 21957728
TI  - Effect of combined administration of enterocin 4231 and sage in rabbits.
AB  - Enterocin (Ent) 4231, produced by non-rabbit origin strain Enterococcus faecium
      CCM 4231 was used in combination with sage plant extract in rabbits with the aim
      to check their antimicrobial activity against microbiota, their effect on
      immunological, biochemical blood parameters, values of volatile fatty acids in
      caecum, Eimeria sp. oocysts occurrence and selected parameters of rabbits meat.
      The animals were divided into three experimental groups (EG1-Ent 4231; EG2- sage;
      EG3- Ent 4231 with sage) and control group (CG); 24 rabbits in each. Natural
      substances (NS) were administered for 21 days. The experiment lasted for 42 days.
      The reduction of microbiota in faeces was observed in EG3 at day 21 by a decrease
      in the numer of coagulase-positive staphylococci (P<0.01) in comparison with that
      determined in CG. The bacterial counts in the caecum were lower than those found
      in faeces. A decrease in the numer of Pseudomonas-like sp. in caeca of the
      experimental groups was observed at days 21 and 42 (difference in range 0.40-1.87
      log cycles) comparing with that determined in CG. At day 21, a significant
      increase in phagocytic activity (PA, P<0.001) was found in blood of rabbits from
      EG2 comparing with that observed in CG. At day 42, a significant increase in PA
      (P<0.001) was determined in all experimental groups in comparison with CG. At day
      21, in caecal content of EG3 significantly higher values of lactic acid were
      observed (P<0.05) in comparison with those found in CG. The reduction of Eimeria
      sp. oocysts was demonstrated after application of each of NS. Addition of NS did
      not influence biochemical parameters, meat quality of the animals and does not
      influence negatively the health status of rabbits.

PMID- 21957729
TI  - The effect of different doses of methisoprinol on the percentage of CD4+ and CD8+
      T lymphocyte subpopulation and the antibody titers in pigeons immunised against
      PPMV-1.
AB  - As immunosuppression in pigeons is common and results in reduced post-vaccination
      immunity and lower health status of the birds, studies have been taken up aimed
      at evaluation of the effect of three doses of methisoprinol on the percentage of
      CD4+ and CD8+ T lymphocyte subpopulation in peripheral blood and in the spleen
      and the titre of anti-NDV antibodies in the serum of pigeons in four groups (A,
      B, C, D), with 20 birds each. Pigeons in each group were immunised against
      paramyxovirosis at week 6 and 9 of life. Water for injection (group A - control)
      or methisoprinol at 100 mg/kg of body weight (group B), 200 mg/kg of body weight
      (group C) and 600 mg/kg of body weight (group D) was administered intramuscularly
      for 3 days before each vaccination. The immunological analyses were carried out
      by flow cytometry and the ELISA test. The findings indicate that methisoprinol
      administered intramuscularly at 100 and 200 mg/kg of body weight for 3 successive
      days before vaccination against paramyxovirosis mainly stimulates the mechanisms
      of non-specific humoral and cellular immunity, which is indicated by a higher
      percentage of the subpopulation of CD4+ T lymphocytes in peripheral blood and in
      the spleen and a higher titre of anti-NDV antibodies.

PMID- 21957730
TI  - The effect of interval versus continuous exercise on plasma leptin and ghrelin
      concentration in young trotters.
AB  - The effect of interval vs. continuous exercise on plasma leptin and ghrelin
      concentration in young Standardbred horses was studied. The experiment was
      conducted on 27 trotters, in the age between 2 and 3 years. They were divided
      into two groups according to the type of exercise. Blood samples were collected
      through jugular venipuncture in the following experimental conditions: at rest,
      immediately after exercise and 30 minutes after the end of the effort. Plasma
      leptin and ghrelin concentrations were determined using RIA tests. The continuous
      exercise induced an increase in plasma leptin concentration whereas the interval
      type of exercise did not influence the level of this hormone (3.47 +/- 0.78 vs.
      4.07 +/- 0.94 and 2.31 +/- 0.15 vs. 2.36 +/- 0.21 ng/mL, respectively). The
      plasma ghrelin concentration measured after the continuous exercise,
      significantly increased (720 +/- 27.4 vs. 814 +/- 13.8; p < or = 0.05) whereas
      concentration of this hormone assessed after the interval exercise, significantly
      dropped (982 +/- 56.5 vs. 842 +/- 35.6 pg/mL; p < or = 0.05). The changes in
      plasma ghrelin concentration measured after the end of the effort correlated
      inversely with blood lactic acid concentration. In conclusion, the obtained
      results showed that medium-intensive type of exercise, such as trot, interval or
      continuous, slightly affected plasma leptin level but significantly affected
      plasma ghrelin concentration in young Standardbred trotters.

PMID- 21957731
TI  - Phylogenetic analysis of canine parvovirus CPV-2 strains and its variants
      isolated in Poland.
AB  - Canine parvovirus disease appeared in the world and in Europe during the second
      half of the 1970s. Over the course of 40 years the original CPV-2 strains mutated
      and variants 2a, 2b and 2c appeared. Their appearance is connected with specific
      amino acid changes, mainly in the capsid protein VP2. Strains isolated by the
      authors were adapted for in vitro cell culture. Phylogenetic analysis revealed
      differences between strains isolated in Poland in 1982-1985 and in 1995-2009.
      Strains from the 1980s were shown to belong to variant CPV-2a (11 strains) and
      variant 2b (2 strains), while no fundamental differences were found among the
      genetic profiles of the strains from 1995-2009, which were classified as
      belonging to variant 2c.

PMID- 21957732
TI  - A comparison of the effectiveness of the microscopic method and the multiplex PCR
      method in identifying and discriminating the species of Nosema spp. spores in
      worker bees (Apis mellifera) from winter hive debris.
AB  - The objective of this study was to compare the effectiveness of the multiplex PCR
      method and traditional light microscopy in identifying and discriminating the
      species of Nosema spp. spores in worker bees from winter hive debris in the
      Province of Warmia and Mazury (NE Poland). A total of 1000 beesdead after from
      the bottom of the hive from bee colonies were analyzed. Spores were identified
      with the use of a light microscope (400-600x magnification). Spores were assigned
      to species by the multiplex PCR method. The microscopic evaluation revealed the
      presence of Nosema spp. spores in 803 samples (80.3%). Nosema ceranae spores were
      observed in 353 positive samples (43.96%), Nosema apis spores were found in 300
      samples (37.35%), while 150 samples (19.67%) showed signs of a mixed infection. A
      multiplex PCR analysis revealed that 806 samples were infested with Nosema spp.,
      of which 206 were affected only by Nosema ceranae, 600 showed signs of mixed
      invasion, while no samples were infected solely by Nosema apis parasites. In two
      cases, the presence of spores detected under a light microscope was not confirmed
      by the PCR analysis. The results of the study indicate that Nosema ceranae is the
      predominant parasitic species found in post-winter worker bees from the bottom of
      the hive in the region of Warmia and Mazury.

PMID- 21957733
TI  - Influence of bestatin, an inhibitor of aminopeptidases, on T and B lymphocyte
      subsets in mice.
AB  - Bestatin, a low-molecular weight dipeptide, is a potent inhibitor of
      aminopeptidase N which has been demonstrated to have antitumor and
      immunomodulatory effects. The effects of bestatin (10, 1 and 0.1 mg/kg)
      administered intraperitoneally once, five or ten times to mice on the total
      number of lymphocytes in the thymus, spleen and mesenteric lymph nodes and the
      percentage and the absolute number of T cell subsets (CD4+CD8+, CD4-CD8-, CD4+,
      CD8+) in the thymus and T (CD3+, CD4+, CD8+) and B (CD19+) lymphocytes in the
      spleen and mesenteric lymph nodes were studied. It has been found that bestatin
      administered ten times at doses of 10, 1 and 0.1 mg/kg increased the total number
      of thymocytes, splenocytes and lymphocytes of mesenteric lymph nodes. Bestatin
      also changed the percentage and the absolute number of T cell subsets in the
      thymus and T and B lymphocytes in the peripheral lymphatic organs. Five and ten
      exposures to bestatin (10, 1 and 0.1 mg/kg) increased the absolute count of both
      immature CD4+CD8+ and CD4-CD8- thymic cells. Moreover, both a single and multiple
      administration of bestatin (1 and 0.1 mg/kg) decreased the percentage and
      absolute count of CD3+ splenocytes and mesenteric lymph node cells with
      corresponding decreases in the percentage and absolute count of CD4+ and CD8+
      cells. Both a single and multiple administration of bestatin at all the doses
      under investigation augmented the percentage and the absolute count of CD19+ (B
      lymphocytes) in the peripheral lymphatic organs. The results of the study show
      that there is a relationship between the effect induced by bestatin and the dose
      of the drug as well as the number of doses applied. The strongest effect on the T
      and B lymphocyte subsets was noted after five injections of bestatin at doses of
      1 and 0.1 mg/kg.

PMID- 21957734
TI  - Antibiotic susceptibility of methicillin-resistant and methicillin-susceptible
      coagulase-negative staphylococci isolated from bovine mastitis.
AB  - The aim of the present study was to evaluate the antibiotic susceptibility of
      methicillin-susceptible (MS) and methicillin-resistant (MR) coagulase-negative
      Staphylococcus (CNS) strains isolated from milk of cows with mastitis. The study
      was conducted on 100 CNS strains (20 MRCNS and 80 MSCNS) isolated from milk
      samples of 86 cows from the Lublin (Poland) region farms. Antibiotic
      susceptibility of microorganisms was evaluated using the disc-diffusion method on
      the Mueller-Hinton agar according to the guidelines of the National Committee for
      Clinical Laboratory Standards (NCCLS). The highest efficacy against MSCNS was
      demonstrated for cephalosporin antibiotics, i.e. cefacetril (91.3%), ceftiofur
      (67.5%), cefoperazone (66.3%) and cephalexin (60.0% of susceptible MSCNS
      strains). Moreover, a high percentage of vancomycin-susceptible strains was
      demonstrated (83.8%). The activity of combination of amoxicillin with clavulanic
      acid and gentamicin was found weaker (63.8% and 61.3% of susceptible strains,
      respectively). About 50.0% of MSCNS were susceptible to erythromycin,
      enrofloxacine and amoxicillin. A large proportion of CNS was resistant to
      neomycin, penicillin, tetracycline, streptomycin, lincomycin and ampicillin
      (28.8%, 30.0%, 31.3%, 31.3%, 33.8% and 33.8% of susceptible strains,
      respectively). The highest percentage of MRCNS was susceptible to vancomycin
      (75.0%), erythromycin (65.0%) and streptomycin (50.0%). Their susceptibility to
      enrofloxacine (35.0%) as well as gentamicin and tetracycline (30.0%) was markedly
      lower. The lowest activity was found for lincomycin and neomycin (20.0% of
      susceptible MRCNS strains, each).

PMID- 21957735
TI  - Myocardial bridges in domestic pig--morphological aspects.
AB  - The morphology of myocardial bridges (MB) in the heart of the domestic pig remain
      an open issue. Despite numerous analyses of the subject, many controversies still
      exist. Opinions also differ when the influence of the MB on haemodynamic
      processes in the coronal vessel system is concerned. In the examined group of 150
      domestic pig's hearts, the length of the detected MB varied from 1.8 to 39.7 mm
      while their thickness amounted to 0.8 - 4.7 mm. Both the longest and the thickest
      bridges were connected with the posterior interventricular branch. It was noticed
      that the MB muscle bands cross the long axis of the vessels located in the
      grooves mostly at almost a right angle. Three forms of perivascular space were
      educed using the criterion of the distance of the vessel from the surrounding
      muscularis externa.

PMID- 21957736
TI  - Growth factor and cytokine interactions in myogenesis. Part I. The effect of TNF
      alpha and IFN-gamma on IGF-I-dependent differentiation in mouse C2C12 myogenic
      cells.
AB  - The aim of this study was to examine the potential interactions of IGF-I with TNF
      alpha and IFN-gamma with regard to regulation of the myogenesis and proliferative
      potential of mouse C2C12 myoblasts. The stimulation of myogenesis by IGF-I (30
      nmol/l) was manifested by an enhanced myoblast fusion and expression of myosin
      heavy chain (MHC) during the first 3 days of differentiation. IGF-I-dependent
      fusion and MHC expression was reduced by TNF-alpha and IFN-gamma. Both cytokines
      prevented the stimulatory effect of IGF-I on MyoD expression with minor
      modification of the myogenin level. Both TNF-alpha and IFN-gamma activated the
      expression of cyclin A in myoblasts restimulated to proliferation; however, when
      used in combination with IGF-I these cytokines prevented the rise in cyclin A
      induced by growth factor. IN CONCLUSION: i) TNF-alpha and IFN-gamma reduce IGF-I
      dependent myogenesis which was manifested by the reduction of myoblast fusion and
      MHC cellular levels, ii) Molecular mechanisms of inhibitory action of TNF-alpha
      and IFN-gamma on IGF-I-mediated differentiation involve a decrease in MyoD
      whereas myogenin level plays a minor role, iii) TNF-alpha and IFN-gamma increase
      the proliferative potential of myoblasts; however, they reduced the mitogenic
      effect of IGF-I, manifested by a decrease of IGF-I-stimulated cyclin A expression
      in myoblasts reinduced to proliferation. Interactions among IGF-I and
      proinflammatory cytokines are therefore important to establish a number of
      myoblasts and the onset of myogenesis during muscle regeneration.

PMID- 21957737
TI  - Growth factor and cytokine interactions in myogenesis. Part II. Expression of IGF
      binding proteins and protein kinases essential for myogenesis in mouse C2C12
      myogenic cells exposed to TNF-alpha and IFN-gamma.
AB  - The aim of the study was to examine potential interactions among IGF-I and
      proinflammatory cytokines, TNF-alpha and IFN-gamma, in the regulation of local
      IGF-I bioavailability and cellular proteins mediating myogenic signals. We
      investigated levels of IGFBP-4, -5, -6, protein kinase Czeta (PKC zeta), p38 and
      extracellular signal-regulated kinase (ERK1/2) in differentiating mouse C2C12
      myoblasts. IGF-I significantly stimulated expression of IGFBP-5. TNF-alpha and
      IFN-gamma attenuated the expression of IGFBP-4 and -6 under basal conditions and
      in the presence of IGF-I, and inhibited IGF-I-induced IGFBP-5 expression during 5
      day myogenesis. TNF-alpha and IFN-gamma markedly attenuated p38 expression in the
      presence of IGF-I on the 5th day of myogenesis. When combined with IGF-I the
      cytokines exerted opposite effects on the PKC zeta level, i.e. TNF-alpha caused
      an increase, whereas IFN-gamma reduced the cellular content of this kinase.
      Exposition of C2C12 myoblasts to IGF-I or cytokines led to the stimulation of
      ERK1/2 phosphorylation; however, both TNF-alpha and IFN-gamma exerted an
      inhibitory effect on the activation of ERK1/2 in myoblasts cultured in the
      presence of IGF-I. We concluded as follows: i) TNF-alpha and IFN-gamma present in
      the extracellular environment of differentiating C2C12 myoblasts can alter the
      local bioavailability of IGF-I by inhibiting the expression of IGFBP-4, -5, and 
      6, ii) the decrease in p38 expression and ERK1/2 phosphorylation in C2C12
      myoblasts exposed to cytokines can lead to disturbances in IGF-I-regulated
      myogenesis.

PMID- 21957739
TI  - Resistance of erythrocytes from brown trout (Salmo trutta m. trutta L.) affected
      by ulcerative dermal necrosis syndrome.
AB  - In the present work we evaluated the effect of ulcerative dermal necrosis (UDN)
      syndrome on resistance of erythrocytes to haemolytic agents and lipid
      peroxidation level in the blood from brown trout (Salmo trutta m. trutta L.).
      Results showed that lipid peroxidation increased in erythrocytes, as evidenced by
      high thiobarbituric acid reactive substance (TBARS) levels. Compared to control
      group, the resistance of erythrocytes to haemolytic agents was significantly
      lower in UDN-positive fish. Besides, UDN increased the percent of hemolysated
      erythrocytes subjected to the hydrochloric acid, urea and hydrogen peroxide.
      Results showed that UDN led to an oxidative stress in erythrocytes able to induce
      enhanced lipid peroxidation level, as suggested by TBARS level and decrease of
      erythrocytes resistance to haemolytic agents.

PMID- 21957738
TI  - Role of extracellular matrix and prolactin in functional differentiation of
      bovine BME-UV1 mammary epithelial cells.
AB  - Interactions between extracellular matrix (ECM) and epithelial cells are
      necessary for proper organisation and function of the epithelium. In the present
      study we show that bovine mammary epithelial cell line BME-UV1 cultured on ECM
      components, commercially available as Matrigel, constitutes a good model for
      studying mechanisms controlling functional differentiation of the bovine mammary
      gland. In contact with Matrigel BME-UV1 cells induce apicobasal polarity, and
      within 16 days form three dimensional (3D) acinar structures with a centrally
      localized hollow lumen, which structurally resemble mammary alveoli present in
      the functionally active mammary gland. We have shown that the 3D culture system
      enables a high expression and proper localisation of integrin receptors and tight
      junction proteins in BME-UV1 cells to be induced. This effect was not obtained in
      cells grown in the classical 2D culture system on plastic. Moreover, ECM highly
      stimulated the synthesis of one of the major milk proteins, beta-casein, even in
      the absence of prolactin. Our results show that contact with ECM plays an
      important role in the lactogenic activity of bovine MECs, however, prolactin is
      necessary for the efficient secretion of milk proteins.

PMID- 21957740
TI  - Comparison of four RT-PCR assays for detection of bovine respiratory syncytial
      virus.
AB  - RT-PCR assays for detection of BRSV, based on four different sets of primers were
      optimized and evaluated for their sensitivity and specificity. Primers used in
      this study were specific for genes encoding three BRSV proteins, nucleoprotein N
      and glycoproteins F and G. Our results indicated that RT-PCR with primers B7:B8
      for G protein was the most efficient in detecting BRSV. Starters B7:B8 reacted
      specifically only with BRSV strains, no cross-reaction with other closely related
      viruses to BRSV was observed. RT-PCR sensitivity was also high and amounted to
      10(1.66) TCID50. Starters for F and N genes of BRSV were not sufficiently
      specific and cross-reacted with RNA of HRSV. RT-PCR with primers for the genes F
      and N of BRSV was characterized by a lower sensitivity than RT-PCR with primers
      B7:B8. In conclusion, RT-PCR specific to a sequence of glycoprotein G gene,
      seemed to be the most useful for BRSV detection.

PMID- 21957741
TI  - Evaluation of selenium status and its distribution in organs of free living foxes
      (Vulpes vulpes) from an Se deficient area.
AB  - The objective of the study was to determine selenium status and its distribution
      in the organs of free living foxes from selenium deficient areas of north-western
      Poland. Samples of organs harvested from 40 foxes shot during the 2008-2009
      hunting seasons served as experimental material. Selenium concentration in the
      organs was determined spectrofluorometrically. Selenium distribution in tissues
      depends largely on its dietary content. Our study indicated that concentrations
      of selenium in the examined organs followed the order:
      kidney>liver>spleen>lung>heart and kidneys were the organ with the highest
      retention of this element. Mean selenium concentration in fox kidneys was 0.60 +/
      0.15 microg/g wet weight. Several times less selenium on average was found in
      the liver (0.27 +/- 0.09 microg/g w.w.), lungs (0.17 +/- 0.06 microg/g w.w.),
      spleen (0.19 +/- 0.06 microg/g w.w.) and heart (0.13 +/- 0.05 microg/g w.w.). All
      the animals studied were deficient in selenium.

PMID- 21957742
TI  - Changes in the quality of meat from roe deer (Capreolus capreolus L.) bucks
      during cold storage under vacuum and modified atmosphere.
AB  - This paper analyses changes in the quality of meat (M. longissimus dorsi) of roe
      deer bucks during 21 days of cold storage (2 degrees C) under vacuum and modified
      atmosphere (MA) conditions (40% CO2/60% N2 and 60% CO2/40% N2). After 21 days of
      storage, meat packaged in a MA with 40% CO2 had higher (P < or = 0.05) L*, a*, b*
      and C* values in comparison with meat stored under vacuum and MA with 60% CO2.
      The mean pH and TBARS values of meat packaged under vacuum and a MA with 40% CO2
      were increasing for the first 7 days of storage, and then they decreased (P < or
      = 0.05). Following storage, the colour of meat became lighter (L*) and more
      yellow (b*). The meat stored under vacuum was characterised by increased (P < or
      = 0.05) cooking loss. During meat storage, a significant increase (P < or = 0.05)
      in total microbial counts and psychrotrophic bacteria was observed.

PMID- 21957743
TI  - Antimicrobial resistance patterns to beta-lactams of gram-positive cocci isolated
      from bovine mastitis in Lithuania.
AB  - The aim of the study was to isolate gram-positive cocci from cows with mastitis
      and to determine their resistance to beta-lactamic antibiotics. Eight hundred and
      nine strains were isolated and identified as staphylococci (n=516), streptococci
      (n=199) and enterococci (n=94) from sub-clinical and clinical cases of bovine
      mastitis in Lithuania. The most common causative agents of udder disease
      included: S. epidermidis (n=176), S. aureus (n=176), S. agalactiae (n=134), S.
      hyicus (136) and E. hirae (n=68). Isolates were analysed for antimicrobial
      resistance to penicillin, ampicillin, amoxicillin, cephalothin, cephalexin,
      amoxicillin + clavulanate. The susceptibility patterns were analysed using the
      agar disk diffusion method. S. aureus showed the highest level of resistance to
      amoxicillin (81.3%), penicillin (76.7%) and ampicillin (78.4%). The corresponding
      values for CNS strains were 59.7%, 59.7% and 50.6% against penicillin, ampicillin
      and amoxicillin respectively. Streptococci were the most frequently resistant to
      amoxicillin (29.3%), and enterococci to penicillin (27%), amoxicillin (27.5%) and
      amoxicillin/clavulanic acid (23.8%). The resistance of all tested mastitis
      pathogens to aminopenicillins and penicillin highly correlated (r=0.83). Compared
      with other antibiotics, amoxicillin and clavulanic acid combination tended to be
      more effective (p<0.05) against all tested bacteria in vitro. However, S. aureus,
      in 38.1% of cases, was resistant to this combination of antimicrobials. This
      study demonstrates that S. epidermidis, S. aureus, S. hyicus, S. agalactiae and
      E. hirae remain the most frequent mastitis causative agents on Lithuanian cattle
      farms. The highest resistance in vitro to penicillins was demonstrated by S.
      aureus, S. hyicus and S. intermedius. Resistance to cephalosporins remains low,
      irrespective of bacterial species of gram-positive cocci.

PMID- 21957745
TI  - White and red blood cells picture in rabbits experimentally infected with RHD
      virus.
AB  - Four strains of RHDV assigned as haemagglutinating (Vt97 and Hartmannsdorf) and
      non-haemagglutinating (Pv97 and 9905) antigenic variants were examined for
      dynamic changes in the values of white and red blood cells indexes. The study
      showed differences among strains examined that were not depending on
      haemagglutination property.

PMID- 21957744
TI  - Prevalence and antimicrobial resistance of Campylobacter in raw milk in the
      selected areas of Poland.
AB  - During the recent years, an immense increase in the number of food poisoning
      cases in people caused by Campylobacter (C.) species has occurred. Raw milk, next
      to poultry meat, is considered the most frequent cause of food poisoning in
      people caused by the subject bacteria, although it is not always possible to
      isolate Campylobacter cells from the incriminated milk. Most probably this
      difficulty is caused by low concentration of the pathogen in milk at the level of
      2/3 cells/ml although even such low concentration represents risk to human
      health. The present study was aimed at determining the occurence of Campylobacter
      bacteria in milk originating from selected regions of Poland. The isolation
      method applied in this work was effective in recovering as few as 0.1 cell of
      Campylobacter per g of food. Among 150 bulk milk samples tested, Campylobacter
      spp. was isolated from 7 (4.6%) ones. The biochemical identification of the
      isolated strains conducted by means of conventional biochemical tests as well as
      by applying the API - Campy tests revealed that all the isolates belonged to the
      C. jejuni species. Determination of resistance to antibiotics was performed by
      means of the diffusion disks method for the following antibiotics: gentamicin,
      ciprofloxacin, ampicillin, chloramphenicol, erythromycin, doxycyclin and
      tetracycline. Among 7 isolates tested, all were susceptible to ampicillin,
      chloramphenicol, erythromycin and gentamicin, 28.5% to doxycyclin and 14.2% to
      tetracycline and ciprofloxacin.

PMID- 21957746
TI  - A comparison of magnetic resonance imaging sequences in evaluating pathological
      changes in the canine spinal cord.
AB  - This paper discusses 28 canine patients subjected to low-field magnetic resonance
      imaging (MRI) of the spinal cord for neurological indications. The authors
      describe and compare the used MRI sequences with an indication of the most
      effective sequences in MRI examinations that require short scanning time. The
      most effective sequences supporting a quick diagnosis of spinal diseases in dogs
      were SE (spin echo), FSE (fast spin echo) and 3D HYCE (hybrid contrast
      enhancement).

PMID- 21957747
TI  - The first report on detection of canine Acantocheilonema reconditum in Poland and
      the associated diagnostic problems.
AB  - Acanthoheilonema reconditum was found during monitoring dogs living in the
      vicinity of Warsaw, for Dirofilaria spp. infection. The microfilaremia in blood
      was at first detected by microscopy and then molecular tests for distinct
      filarial markers were performed. PCR product sequencing confirmed that the
      microfilaria detected in two dogs were A. reconditum. These are the first two
      cases of canine acanthocheilonemiasis detected in Poland.

PMID- 21957748
TI  - Characteristics of selected seminal plasma proteins and their application in the
      improvement of the reproductive processes in mammals.
AB  - Understanding the biochemical processes associated with ovum fertilization and
      knowledge about the structure and function of individual substances participating
      in these processes is crucial for the development of biotechnological methods to
      improve reproduction of animals and humans. Among many components of seminal
      plasma, proteins and peptides play a specific role in regulation of the
      fertilization process, particularly through their ability to bind various types
      of ligands such as polysaccharides, lipids and ions. Heparin-binding proteins
      regulate capacitation and acrosome reaction processes. Affinity of plasma
      proteins to mannans of the fallopian tube epithelium facilitates formation of
      spermatozoa reservoirs in the female reproductive tract. Ability to bind
      phosphorylcholine is one of the conditions for the coating of the seminal plasma
      proteins on the sperm membrane and also determines the formation of oligomeric
      forms of certain proteins. Zinc binding by seminal plasma proteins regulates
      sperm chromatin condensation state. It also affects motility of these cells and
      acrosome reaction. The interspecies analysis indicates significant structural and
      functional similarities, especially for the proteins with low molecular weight.
      Fertility associated proteins (FAPs) have been determined in the bull, stallion,
      boar, ram and dog. The contents of these proteins correlate with the indicators
      of the fertilizing abilities of sperm. In humans, several seminal plasma proteins
      were found which serve as diagnostic markers of spermatogenesis, seminiferous
      epithelium state, and azoospermia. To determine the semen ability for
      preservation, measurement of some seminal plasma protein content may also be
      used. Addition of specific plasma proteins to a spermatozoa solution undergoing
      the process of preservation may be used to retain the features of the cells
      responsible for efficient fertilization.

PMID- 21957749
TI  - Magnetic resonance imaging of selected limb joints in dogs.
AB  - The presented paper presents updated information concerning magnetic resonance
      imaging (MRI) of shoulder joint, elbow joint and knee joint in dogs. It describes
      indications, planes, standard sequences, slice thickness to perform MRI
      examination of above mentioned joints. Besides general information about basic
      physics use in magnetic resonance imaging, and practical information about
      magnetic resonance and it usage in orthopedic examination are given.

PMID- 21957750
TI  - Natural orifice transluminal endoscopic surgery (NOTES) in animals.
AB  - Natural orifice transluminal endoscopic surgery (NOTES) is a modern technique of
      performing surgical procedures developed worldwide. In the last few years, series
      of NOTES operations were performed in animals and humans. This article describes
      some surgical procedures performed in animals with use of this new technique.

PMID- 21957751
TI  - Monocytic ehrlichiosis in dogs.
AB  - Ehrlichiosis is the multiorgan infectious disease caused by small, intracellular
      rickettsias from the genus Ehrlichia. These microorganisms are known as an
      etiologic factor of infections world wide in humans and in different species of
      animals. Dog ehrlichiosis can be caused by several species of Ehrlichia attacking
      different groups of blood cells, but most often an infection by Ehrlichia canis
      is diagnosed with special relation to monocytes. A vector for E. canis are
      Rhipicephalus sanguineus and Ixodes ricinus, commonly occurring in Poland.
      Disease caused by E. canis is known as Canine Monocytic Ehrlichiosis (CME). The
      disease most often has an asymptomatic course which can, in favourable
      circumstances, run into acute or chronic forms. The acute form of CME proceeds
      usually with fever, apathy, weakness and accompanying respiratory symptoms,
      lameness and disturbances in blood coagulation. In laboratory examinations
      thrombocytopenia, anemia and leucopenia are ascertained. The chronic form of CME
      proceeds among gentle, unspecific symptoms which may last even 5 years. The CME
      diagnosis is difficult and often demands parallel different diagnostic methods. A
      medicines of choice in the ehrlichiosis treatment are antibiotics from the group
      of tetracyclines, given at least for 28 days. They are largely efficient during
      treatment of the acute CME, causing the quick improvement. Instead, in the case
      of chronic form, answer for treatment can be weak, and cases of resistance to
      antibiotics ave known.

PMID- 21957752
TI  - The Colorado Crisis Education and Response Network: an analysis of policy and
      practices.
AB  - The Federal government has recognized the importance of including behavioral
      health in disaster response plans and policies. Many states have responded to
      these directives with the development and implementation of disaster behavioral
      health response teams. The Colorado Crisis Education and Response Network
      (CoCERN) is a statewide asset that is based in community partnerships formed to
      deliver effective, efficient, and professional disaster behavioral health
      services to communities impacted by a disaster Using the K. McInnis-Dittrich
      model of policy analysis, this paper analyzes this approach to disaster
      behavioral health response. Strengths and weaknesses of the program, as well as
      implications for practice are discussed.

PMID- 21957753
TI  - Psychological distress following wildfires disaster in a rural part of Greece: a
      case-control population-based study.
AB  - Psychological distress is common in the aftermath of a disaster. This study
      investigated psychological distress and morbidity in individuals who had
      experienced severe exposure to a wildfire disaster in a part of Greece. The study
      was a cross sectional case control of an adult population (18-65 years old). Face
      to face interviews were used in the collection of the data which were
      demographics, the type and number of losses and the Symptom Checklist 90-Revised
      for assessment of psychological symptoms. The results showed that those exposed
      to wildfires disaster scored significantly higher on the symptoms of
      somatization, depression, anxiety, hostility, phobic anxiety, and paranoia; had
      significantly more symptoms of psychopathology and were more distressed, compared
      to controls. Risk factors for potential psychiatric cases were those exposed to
      disaster; those who had lower education, and those who were widowed. It was
      concluded that wildfires may cause considerable psychological symptoms comparable
      to other disasters and there are reasons to create services to help and improve
      the mental health of those affected.

PMID- 21957754
TI  - Mental health screening at temporary military health clinics in low income
      Hispanic communities within the Rio Grande Valley of Texas.
AB  - Behavioral and mental health problems are not always considered in temporary
      medical clinics nor are instruments readily available to provide medical
      practitioners in these settings with information relevant to mental health
      conditions. This study provided preliminary data on the utility of the Mini
      Mental Screen in temporary military medical clinics in the Texas Rio Grande
      Valley. This instrument was administered to individuals who may have behavioral
      or mental health problems. In a sample of mostly Hispanic patients (N = 75) seen
      at a temporary medical clinic, 12% were at significant risk of mental health
      problems, with an additional 9% at moderate risk using published cut-off scores
      for the risk of such problems. The results for each patient were provided to a
      medical practitioner who further evaluated the risk, treated the problem, or made
      a referral. When asked, three of four medical practitioners found that screening
      data was helpful in their work with patients. One practitioner was concerned that
      the screening instrument might have too high a false positive rate to be useful.
      Cultural issues of openness about mental health and behavioral problems need to
      be considered in such settings.

PMID- 21957755
TI  - Police organizational stress: the impact of negative discipline.
AB  - Previous work has suggested that the police organization is considered a
      difficult work stressor by officers. Of stress factors stemming from the police
      organization, excessive or unfair discipline rates high among rank and file
      officers. The police organization may be considered a punishment centered
      bureaucracy, where emphasis is placed on what is wrong and not on proper or
      laudatory behavior Although discipline is essential in critical occupations such
      as police work, it is important that such discipline be properly administered in
      order to avoid stress and feelings of organizational abandonment. This paper
      provides a general overview of present police organizational discipline
      prescriptions, and an example of an alternative positive-based discipline
      program.

PMID- 21957756
TI  - Suicide intervention: basic processes and strategies.
AB  - Dealing with a subject in suicidal crisis requires a certain set of communication
      and empathic skills. This article outlines some facts and misconceptions about
      suicide, then describes some practical intervention strategies from the fields of
      crisis intervention and emergency mental health.

PMID- 21957757
TI  - [Czech angiology and its transformation].
AB  - Over the last 25 years, Czech angiology has changed dramatically with respect to
      the diseases and conditions managed by angiologists as well as available
      therapeutic modalities. Such developments also required substantial expansion of
      the extent and character of specialist knowledge required from angiologists.
      Angiology manages to effectively correlate a clinical profession with non
      coronary endovascular therapy and this has brought about a significant
      improvement in treatment efficacy and comfort. Physicians thus crossed a boundary
      of purely conservative treatment and focus on life and organ-threatening vascular
      diseases. Recent years have also seen an emergence of sub-specialities
      ofinterventional and acute angiology. The use of diagnostic and therapeutic
      catheterisation enabled angiologists to contribute to the care of patients
      previously managed by vascular surgeons and interventional radiologists;
      angiologists have become important contributors to the medical care provided by
      comprehensive cardiovascular centres.

PMID- 21957758
TI  - [Irritable bowel syndrome].
AB  - Irritable bowel syndrome is a frequent functional disorder of gastrointestinal
      tract. Its high incidence represents an important socioeconomic concern. The
      diagnosis of irritable bowel syndrome is indirect and requires exclusion of an
      organic lesion within as well as outside the gastrointestinal tract. No
      algorithms--so called treatment guidelines--are available for pharmacological or
      non-pharmacological treatment of the irritable bowel syndrome. Long-term and
      comprehensive care of patients with functional diseases is an important component
      of the management of patients with irritable bowel syndrome.

PMID- 21957759
TI  - [Biological treatment in dermatology--psoriasis].
AB  - Psoriasis is a chronic, relapsing skin disease affecting 1-2% of the population.
      Genetically-determined autoimmune inflammation is initiated by an infection (e.g.
      streptococcal). T-lymphocytes, producing a number ofcytokines, mainly of the Th1
      profile, including TNF alpha, play a key role. The role of Th17 and its
      interleukin IL-23 has recently been confirmed. It contains p40 protein, also a
      component of IL-12. TNF alpha and p40 blockade appear to be an effective
      biological treatment of severe lesional psoriasis. Further research and new drug
      development is to assure modern individualized treatment of psoriasis as well as
      other skin diseases.

PMID- 21957760
TI  - [Prokinetic agents--their contribution to practice of gastroenterology].
AB  - Motility plays a fundamental role in the functioning of the gastrointestinal
      tract. Prokinetic agents are thus an important treatment modality in patients
      with functional and certain organ diseases with underlying functional
      modifications. Gastro-oesophageal reflux disease is frequently associated with a
      disorder ofoesophageal motility, an alteration of gastric evacuation may manifest
      as an atypical dyspeptic complaint. Prokinetic agents may also be effective in
      other disease states, such as diabetic gastroparesis, malignant conditions
      associated with nausea and vomiting, motility disorders in preterm babies etc.

PMID- 21957761
TI  - [Liver diseases in internal medicine outpatient clinics].
AB  - Patients with a suspected or confirmed liver disease are frequent attendees at
      internal medicine outpatient clinics. Metabolic and toxic liver lesions are
      presently much more prevalent than infectious liver diseases. Liver steatosis and
      drug-induced liver impairment are the most frequent. The main task for internal
      medicine specialists in primary care with respect to chronic viral hepatitis B
      and C is to keep these diseases in mind and when an increased
      alaninaminotranspherase activity is detected, to perform blood tests for the
      presence of HBsAg as well as anti-HCV antibodies. Epidemiologically high-risk
      patients should always be tested for the presence of HBsAg and anti-HCV (even
      with normal ALT activity).

PMID- 21957762
TI  - [Arrhythmology today: risks associated with anti-arrhythmic therapy in an
      internal medicine outpatient clinic].
AB  - Arhytmology that is focused on diagnostics and therapy of heart rhythm
      disturbances and their complications has undergone dramatic development in last 2
      decades. Widespread use of catheter ablation, introduction of implantable
      cardioverter-defibrillators for prevention of sudden cardiac death and finally,
      development of cardiac resynchronization therapy have lead to decreased
      importance of drug treatment. Antiarhythmic drugs remain therapy of choice in
      management of atrial fibrillation and in some ventricular arrhythmias, especially
      in patients with implantable cardioverter-defibrillator backup. Therefore, this
      review deals predominantly with a strategy of antiarythmic therapy in atrial
      fibrillation and discusses possible risks.

PMID- 21957763
TI  - [Treating stable chronic obstructive pulmonary disease (COPD) and its potential
      cardiovascular risks (a basic overview)].
AB  - Chronic obstructive pulmonary disease (COPD) is a highly prevalent clinical
      syndrome. It affects a significant proportion of world population, including non
      smokers. The number of COPD patients continues to grow. For many reasons, COPD is
      often associated with a heart disease. In some patients, a heart disease is the
      primary pathology, in others COPD develops first, while sometimes heart and
      pulmonary involvement occur more or less simultaneously. As yet we are unable to
      repair damaged pulmonary parenchyma or to restore capillary destruction occurring
      around pulmonary alveoli. Furthermore, the disease development cannot be
      completely suppressed. However, outpatients may be offered a range of treatment
      interventions leading to slower COPD progression, improvement in quality of life
      and longevity, and symptom and acute exacerbation risk reduction. The main aim of
      the paper is to present current perceptions of COPD and to discuss potential
      cardiovascular risks of the treatments used.

PMID- 21957764
TI  - [Criteria for perioperative risk evaluation--non-cardiac surgery].
AB  - The paper presents criteria used to evaluate surgical risks associated with non
      cardiac surgical procedures.

PMID- 21957765
TI  - [Current perspective of treating hypertension in pregnancy].
AB  - The author deals with the contemporary perspective on treatment hypertension in
      pregnancy. The article highlighted that hypertension treatment should be
      conducted not only with regard to the mother, but also to the possible negative
      impact on supply to the fetus. New information, particularly in the
      pathophysiology of pregnancy related hypertension show that in these diagnoses is
      vasoconstriction in placental microcirculation quite common. Inadequate treatment
      may have adverse effects on uteroplacental flow with potential risks to the
      fetus. The treatment of choice in pregnancy relatedy hypertension are methyldopa,
      calcium antagonists and labetalol.

PMID- 21957766
TI  - [New antithrombotics in the prevention of venous thromboembolia and new anti
      platelet drugs].
AB  - We first present a brief overview of new antithrombotic agents that are assumed
      to replace coumarines and heparin in many indications; this overview provides
      information on pentasaccharides, direct thrombin inhibitors and direct factorXa
      inhibitors. Secondly, since the new drugs with antiplatelet effect act through
      blockade of the reactions involved in blood platelet activation, we review and
      discuss the substances that interfere with this process. The current antiplatelet
      therapy focuses mainly on an inhibition of platelet aggregation stimulated by
      ADP, reducing the risk of arterial occlusions.

PMID- 21957767
TI  - [Targeted biological treatment of solid tumours].
AB  - Clinical use of targeted biological treatment was initiated in 1970s following a
      discovery of hormonal receptors and targeted clinical use of tamoxifen. Deeper
      understanding of molecular principles of the process of metastasizing and cell
      communication and signalling have contributed to the development of targeted
      molecular biological treatments based on direct impact on the key target
      structures ofa tumour cell. Clinical effectiveness of targeted biological
      treatment has been shown in phase III clinical studies in advanced and
      metastasising solid tumours and importantly expanded our armamentarium of
      pharmacotherapeutic treatment options in breast cancer, colorectal cancer, non
      small cell lung cancer, kidney cancer, hepatocellular carcinoma and
      gastrointestinal stromal tumour. Full implementation of targeted therapy is
      precluded by a lack of reliable predictors of efficacy of a number of targeted
      drugs. Therefore, full identification of such predictors is a subject to
      intensive clinical research. At present, selection of biological treatment is
      based on morphological, immunohistochemical and partly also molecular profile ofa
      tumour. The future of biological treatment lies in a selection that is based on
      full molecular characterization of the primary tumour as well as metastasis.

PMID- 21957768
TI  - [Proteinuria in primary care].
AB  - Proteinuria is one of the main symptoms of renal impairment. It may manifest
      itself as a small amount of albumin in the urine (microalbuminuria) or as the
      nephrotic syndrome. Testing strips results should be considered as preliminary; a
      negative result does not exclude renal disease. At present, proteinuria is
      assessed as a total protein waste in the urine collected over 24 hours with up to
      150 mg/day being considered a norm. Lately, the protein (albumin) to creatinine
      ratio in a sample of morning urine is being preferred (protein/creatinine ratio -
      PCR or albumin/creatinine ratio - ACR). More detailed nephrological examination
      should be performed if these reach pathological values (PCR > 15 mg/mmol a ACR >
      3.5 mg/mmol). These assessments are not burdened by the same variability of
      values as with the 24-hour urine collection. A number of studies provided
      evidence on the role of proteinuria (as well as microalbuminuria) in accelerating
      a decline in glomerular filtration as well as its role as a risk factor of total
      and cardiovascular mortality. Therefore, this issue should receive appropriate
      attention and patients who are in a higher risk of renal impairment should be
      intentionally sought. These include diabetics, patients with heart disease,
      hypertension and patients with known personal or family history of renal disease.
      Only when a renal disease (and proteinuria is a clear symptom) is detected in
      time, targeted or symptomatic treatment can by initiated to slow down or even
      halt the disease progression to end stage renal disease. Despite this, more than
      1/3 of patients entering chronic dialysis treatment have not been monitored. This
      significantly increases their morbidity and mortality, particularly within the
      first year of dialysis. General practitioners as well as internal medicine
      specialists, cardiologists and diabetologists play a fundamental role in
      screening of the high risk population.

PMID- 21957769
TI  - [The importance of antihypertensive therapy in subclinical brain damage].
AB  - Older patients are often affected by impaired cognitive function and high blood
      pressure. Damage to microcirculation of the brain is closely related to changes
      in large vessels. High blood pressure and vascular stiffness might lead to a
      damage in microcirculation of the brain and, consequently, to worsening of the
      patient's cognitive function and dementia. We discuss early diagnosis of
      subclinical brain damage using magnetic resonance and its preventive management
      with antihypertensive therapy.

PMID- 21957770
TI  - [Polypharmacy and drug interactions].
AB  - The growing consumption of drugs and other numerous factors relates to the
      increasing incidence of polypharmacy. The proportion of patients currently
      treated with 5 or more medicines at the elderly population in particular is 30
      60% of patients. Repeatedly has been proven the dependence between the number of
      concomitant drugs and occurrence of adverse effects, patients requiring
      hospitalization, or incidence of moderate and serious drug interactions. Some
      works show that it is possible to satisfactorily address the issues of
      polypharmacy, but it requires great courage and an interdisciplinary approach
      involving modern information technology.

PMID- 21957771
TI  - [Is there any relation between diabetes therapy and cancer risk?].
AB  - Type 2 diabetes is associated with increased risk of cancer. This risk is related
      to HbA1 increase and this influence is present also in prediabetes and in
      nondiabetics with HbA1c in upper normal range. In last 2 years, it was concluded
      that that the specific antidiabetic therapy could influence the cancer risk. In
      this review we show that reduction of HbA1c does not change cancer risk. Most
      important is the risk reduction of cancer risk by metformin. Insulin therapy and
      the use ofsulphonylurea related drugs, increases the risk of cancer. This risk
      can be eliminated in the combination with metformin. Other published results
      including the suspected effect related to the use of glargine, pioglitazone,
      sitagliptine and exenatide are inconsistent and analysis of long term effects of
      these drugs is necessary. The large discussion in many publications shows the
      important role of FDA and EMA. This agencies do not suspend drugs without
      consistent evaluation of results.

PMID- 21957772
TI  - [Combined exercise training in men with metabolic syndrome after acute coronary
      event].
AB  - INTRODUCTION: Favourable effect of exercise training on cardiovascular prognosis
      in patients with metabolic syndrome have been documented in lot of studies. Less
      information exist about results of cardiovascular rehabilitation in patients with
      different forms of coronary heart disease and associated diseases and
      abnormalities within metabolic syndrome. METHODS: The present article evaluates a
      benefit of combined, aerobic-resistance training in two groups of patients after
      percutaneous coronary intervention for acute coronary syndrome: with [group
      MS(+), n = 42] and without [group MS(-), n = 53] metabolic syndrome. The changes
      in aerobic capacity (VO2 peak, VO2 peak . kg(-1)), physical performance (W peak,
      W peak . kg(-1)), blood pressure, BMI and waist circumference after 12 weeks of
      cardiovascular rehabilitation are evaluated. RESULTS: Significant improvement in
      aerobic capacity and physical performance were found out both in group MS(+) and
      MS(-) (p < 0.01, resp. p < 0.001). Decrease of systolic blood pressure was
      significant in MS(+), whereas in MS(-) together with decrease of diastolic BP in
      both groups were not significant. The increase in aerobic capacity and physical
      performance in patients of MS(+) is comparable with those in MS(-); the decrease
      in systolic BP was more intensive in MS(+) compared to MS(-). The changes in
      waist circumference and BMI were not significant in both groups. CONCLUSION: The
      results show, that in patients with high number of risk factors associated with
      metabolic syndrome was demonstrated at least comparable benefit from
      cardiovascular rehabilitation compared with those without metabolic syndrome.

PMID- 21957773
TI  - [Diagnostic of secondary hypertension in clinical practice].
AB  - Arterial hypertension is a common worldwide disease with a prevalence of
      approximately 26%. Secondary cause is known in 5-10% of patients with
      hypertension. We should think of secondary hypertension in all patients with
      resistant hypertension, in patients with sudden deterioration in the control of
      hypertension and in patients with laboratory and clinical signs of diseases
      associated with secondary hypertension. It is important to distinguish between
      secondary hypertension and pseudo-resistance (noncompliance to treatment, white
      coat syndrome). Secondary causes of hypertension can be divided into endocrine
      (primary aldosteronism, pheochromocytoma, hypercortisolism,
      hyperparathyreoidism), renal - renovascular and renal parenchymal hypertension,
      and other causes as sleep apnoe syndrome, hypertension in pregnancy, coarctation
      of the aorta and intracranial tumors.

PMID- 21957775
TI  - [Thyreopathy in primary care].
AB  - Thyroid gland disorders, as the core of all endocrinopathies, affect 5-7% of the
      population of the Czech Republic, with women being affected 6-8 times more often
      than men. Clinically, thyreopathies are divided into hormonal production
      disorders and morphology disorders. Thyroid hormones fT3, fT4 and TSH serum
      levels determine the diagnosis of a thyroid gland disorder. Primary hypothyreosis
      is characterized by reduced fT4 and increased TSH. Low T3 syndrome is a
      protective reaction of the organism and is associated with conversion of T4 into
      hormonally inactive triiodothyronine (rT3). Primary hyperthyreosis is
      characterized by higher fT4 and low TSH levels. Acute thyreoiditis: Inflammatory
      signs and normal thyroid function, anti-TPO as well as anti-TG are not elevated.
      Subacute thyreoiditis is manifested as an inflammation, normal anti-TPO and anti
      TG, sometimes also hyperthyreosis. Chronic thyreoiditis, Hashimoto's struma is
      among the most frequent causes ofhypothyreosis in the Czech Republic and it is
      diagnosed through high anti-TPO and anti-TG levels and higher TSH. Thyreoidal
      adenomas and carcinomas are clinically usually euthyroid. Determination of tumour
      markers - thyreoglobulines in papillary and follicular carcinomas and calcitonin
      in medullar carcinoma that requires genetic assessment (determination of germinal
      mutations, usually with PCR)--is essential.

PMID- 21957774
TI  - [FARIM - FARmakoterapie po Infarktu Myokardu (Post-Myocardial Infarction
      Pharmacotherapy Study)].
AB  - A total of 2,500 patients with an anamnesis of myocardial infarction at least 1
      month prior to inclusion in the study who visited a general practitioner or an
      internal medicine or cardiology specialist were examined. Through an internet
      based portal, physicians entered patient data, their complaints, treatment, blood
      pressure, heart rate and main biochemical parameters. There were more men (1 787
      vs. 713) and patients under 70 years of age (1 491 vs. 1 009) in the cohort.
      Eighteen percent of patients had more than one MI. Mean age at the first
      infarction was 59.2 years in men and 64.9 in women (p < 0.001). NYHA
      breathlessness category higher than II was reported by 13.0% of patients only,
      57.2% of patients reported they never had chest pain following an MI.
      Hypertension was the most frequent co-morbidity (84%). The mean blood pressure
      was 132/79 mmHg with no difference between men and women, the mean heart rate was
      68/min, the mean cholesterol level was 4.55 mmol/l. 66% of patients had been
      prescribed all recommended pharmacotherapeutic groups according to guidelines
      (RAAS blockers, beta-blockers, statins, antiaggregation agents) and each group
      individually was used in > 90% of patients. There were no differences between men
      and women and older and younger patients. ACE inhibitors and statins were not
      always prescribed in recommended (high) doses. Ramipril and perindopril were the
      most frequently prescribed ACE inhibitors and atorvastatin the most frequently
      prescribed statin. There was a high level of compliance when it came to achieving
      the target blood pressure and heart rate values as well as to prescribing of the
      recommended drug groups. However, renin-angiotensin system-blocking agents and
      statins are not being prescribed in sufficiently high doses and this should be
      improved.

PMID- 21957776
TI  - An abbreviated history of osseous surgery.
AB  - Various forms of periodontal therapy, including surgery, have been advocated and
      documented in the dental literature during the last three centuries. This variety
      of treatment modalities has been developed to address the anatomical consequences
      (pocket formation and bone loss) sustained from chronic periodontal disease. The
      marked differences in techniques have created significant controversies between
      the greatest leaders in dentistry and their equally influential disciples.
      Nevertheless, these leaders have always shared a common goal: the preservation of
      the natural dentition in a harmonious environment of health, comfort, and proper
      function. This article discusses the history of periodontal osseous surgery,
      including not only the technical issues, but also the conceptual underpinnings of
      this form of therapeutic intervention. In the process of examining this subject
      closely, three main controversies in the field of periodontics are brought into
      sharper focus: non-surgical versus surgical periodontal therapy; gingivectomy
      versus osseous resective periodontal therapy; and the nature of clinical decision
      making: scientific and evidenced-based versus subjective clinical judgement.

PMID- 21957777
TI  - Local anesthetics, pulpal blood flow and C. Edmund Kells.
AB  - Historically there was an attempt by many dental practitioners to implicate
      anesthetic solutions in the death of the dental pulp. However, their implications
      may or may not have been valid, as damage to the dental pulp may have resulted
      from excessive and deleterious restorative procedures on teeth that were
      anesthetized. Unfortunately little was known about the anesthetic solutions at
      that time, their composition, which included vasoconstrictors, and their
      potential to alter pulpal blood flow. This paper will explore both the historical
      perspectives and concerns regarding the impact of anesthetic solutions on the
      dental pulp through the eyes of Dr. C. Edmund Kells, along with the contemporary
      perspectives and realities through the eyes of science, sound research data and
      clinical practice.

PMID- 21957778
TI  - The history of dental hygiene in South Korea.
AB  - This historical narrative highlights the origin and development of the dental
      hygiene profession in South Korea. The legacy of early American missionaries to
      Korea includes profound and long-lasting contributions in medicine, education and
      theology. Many of Korea's top universities today have their roots in the
      missionary schools of the late nineteenth century, including Yonsei University,
      home of the first dental hygiene program in Korea. From Yonsei in Seoul, the
      dental hygiene profession spread throughout the country, includingtheAmerican
      missionary-based program in Kwangju in 1977. Contributions included clinical and
      didactic education, as well as professional leadership and development. American
      dental missionaries developed the profession of dental hygiene in Korea, and
      provided guidance to Korean dentists and hygienists for its growth and expansion.

PMID- 21957779
TI  - Dental ethics "the strength of our profession".

PMID- 21957780
TI  - President's message.

PMID- 21957781
TI  - Ethics education in undergraduate pre-health programs. The contribution of
      undergraduate colleges and universities to the ethical and moral development of
      future doctors in the medical and dental professions.
AB  - There are many barriers to ethics education of students attending medical and
      dental schools. The question is asked, "Should more attention be given to
      addressing students' ethics education during their undergraduate years of
      preparation for professional healthcare programs?" This qualitative study
      utilizes digitally recorded personal interviews with two undergraduate pre
      healthcare students, one medical student, one recently matriculated dental
      student, one undergraduate pre-healthcare faculty member, three dental school
      faculty members, and three medical school faculty members. Interview participants
      discuss areas of personal knowledge and experience concerning: the admissions
      process and screening of potential medical/dental students for ethical traits and
      behaviors, influences on student ethical development, undergraduate pre
      healthcare ethics training, and preferred college major for pre-healthcare
      students. The study concludes that undergraduate pre-healthcare programs should
      take the initiative to be proactive and deliberate in strengthening the positive
      influences on students. Strategies include: 1) humanities curricula to broaden
      perspectives and increase non-prejudice; 2) mentoring and modeling by older
      students, faculty, and community and professional volunteers; 3) ethical case
      study discussions in class or extracurricular activities; and 4)
      volunteer/service learning activities. Additionally, curriculum learning is
      enhanced by the use of reflection and writing, discussions, and media.

PMID- 21957782
TI  - Teaching ethics and change.

PMID- 21957783
TI  - The journey beyond silos. Teaching and learning interprofessional ethics at
      UTHealth.
AB  - Interprofessional education and ethics education are two educational programs
      that blend together well, and, moreover, they are a natural fit for teaching in
      an academic health science center. The purpose of this paper is to describe our
      recent journey of developing and implementing an interprofessional ethics
      curriculum across the six schools of UTHealth. We provide an overview of the
      goals of the Campus-wide Ethics Program, which is housed in the McGovern Center
      for Humanities and Ethics, and we highlight certain innovative developments that
      are the result of the collaborative work of faculty and administrators from all
      six schools of UTHealth. In addition, a brief synopsis of the specific didactic
      and clinical courses in which ethics is a significant component is outlined for
      both the dental and the dental hygiene curricula. Lastly, we describe some of the
      recent scholarly activities that are a product of this new program. We are
      excited about our evolving efforts and the potential benefits of weaving
      interprofessional ethics within our school and across our campus. This article
      tells the story of our journey beyond "the silos" that are common among academic
      health science centers.

PMID- 21957784
TI  - ADA Principles of Ethics and Code of Professional Conduct.

PMID- 21957785
TI  - The judicial process: an overview from the TDA Council on Ethics and Judicial
      Affairs.
AB  - From time to time, the Council on Ethics and Judicial Affairs must investigate
      and act on the alleged unethical behavior of Texas Dental Association members.
      Because the alleged behavior is directed at a colleague and TDA member, the work
      of the council is neither comfortable nor inviting. Nonetheless, council
      decisions are made taking into account its mission to investigate the allegation
      between the parties and to improve dental ethics in the state.

PMID- 21957786
TI  - Conflicts of interest.

PMID- 21957787
TI  - The TDA self-regulation processes.

PMID- 21957788
TI  - Texas State Board of Dental Examiners disciplinary matrix.

PMID- 21957789
TI  - Overtreatment or appropriate treatment?

PMID- 21957790
TI  - Transferring records of the demanding patient.

PMID- 21957791
TI  - Laser frenectomy postoperatively less uncomfortable than scalpel frenectomy (UT
      CAT0769).

PMID- 21957792
TI  - Oral and maxillofacial pathology. Case of the month. Van der Woude syndrome
      (VWS).

PMID- 21957793
TI  - Value for your profession. Monitoring breathing in the sedated patient: three
      ways to do it, and tools to help you.

PMID- 21957794
TI  - A world of emergencies.

PMID- 21957795
TI  - Shifting life rhythms: Couples' stories about living together when one spouse has
      advanced chronic obstructive pulmonary disease.
AB  - AIM: This study examines couples' experiences of living together when one partner
      has advanced chronic obstructive pulmonary disease (COPD). METHOD: Repeated
      qualitative interviews with four couples over an eight-month period, where one
      spouse in each couple suffered from advanced COPD. The final dataset comprised 19
      interviews. A phenomenological-hermeneutical method was used to interpret the
      interview text. FINDINGS: One main theme, "living with the disease and one's
      spouse in a new and changeable life rhythm", emerged from three subthemes:
      "living with uncertainty", "living in a changed intimate relationship", and
      "finding new ways of living together". A mutual sense of companionship between
      the spouses facilitated their chances of reshaping their relationship and
      adapting it to the new life rhythm required by everyday life with the disease.
      CONCLUSION: The healthy spouse had major responsibility for the health of their
      sick spouse. Awareness of the couple's own conceptions and knowledge of health
      and illness is central to person-focused care, as is awareness of what values are
      important to them when restructuring their everyday life.

PMID- 21957796
TI  - Decision-making for gastrostomy and ventilatory support for people with motor
      neurone disease: variations across UK hospices.
AB  - Interventions, such as the use of percutaneous endoscopic gastrostomy (PEG) and
      non-invasive ventilation (NIV), are used in the management of people with motor
      neurone disease with the aim of improving quality of life and relieving symptoms.
      However, the number of people receiving these interventions varies across the UK.
      This study has looked at the involvement and knowledge of consultants, within
      specialist palliative care services, with these procedures, to ascertain if there
      were differences in attitudes to their use. Twenty-two consultants took part in a
      telephone audit. There appeared to be great variation in their involvement in and
      knowledge of the use of these interventions. The majority of services were
      involved in the care of people with MND, but often only in the terminal stages.
      There appears to be a need for the wider application of guidelines on the use of
      PEG and NIV, as well as the development of a collaborative approach with other
      services, including neurology and rehabilitation services.

PMID- 21957797
TI  - Professional development: Iranian and Swedish nurses' experiences of caring for
      dying people.
AB  - Our world is rapidly becoming a global community. This creates a need for us to
      further understand the universal phenomena of death and professional care for
      dying persons. A transcultural study was undertaken using a phenomenological
      approach to illuminate the meaning of nurses' experiences of professional
      development in the contexts of Iran and Sweden. Eight registered nurses working
      in oncology units in Tehran, Iran, and eight working in the context of a hospital
      and private homes in northern Sweden were interviewed. The interviews were
      analyzed using the principles of phenomenological hermeneutics inspired by Paul
      Ricoeur. A naive reading guided a structural analysis, which yielded four main
      themes: coping with existential, organizational, and cultural contexts; sharing
      knowledge, experiences, and responsibilities; using embodied knowledge; and
      developing personal competence. The interpreted comprehensive understanding
      revealed that the meaning of professional development is that it actualizes other
      oriented values and self-oriented values. Caring professionally for dying people
      was a learning process that could help nurses to develop their personal and
      professional lives when they were supported by teamwork, reflective practice, and
      counselling.

PMID- 21957798
TI  - Evaluating the economic loss of caregiving for palliative care patients.
AB  - OBJECTIVE: Our aim is to provide a unified measure of the economic burden faced
      by families during the palliative phase of care and to compare this measure to
      Statistics Canada's low-income cut-off. METHODS: Samples of palliative care
      patients living at home and their main informal caregivers were recruited in five
      Canadian urban regions. Interviews were performed every two weeks until the
      patient's passing, up to a maximum of six months. Participants were asked to
      provide details about their expenses and their absences from work that related
      specifically to the patient's condition. Income loss was evaluated for 192 family
      units. RESULTS: About 9 percent of families incurred economic losses in excess of
      10 percent of their pre-study gross annual income; low-income status increased
      from 27 (before) to 40 (after). CONCLUSION: This is the first study to provide a
      unified measure of economic losses of caregiving that can be related to a
      publicly designated low-income threshold.

PMID- 21957799
TI  - The effect of palliative daycare on hope: a comparison of daycare patients with
      two control groups.
AB  - BACKGROUND: Despite expansion in palliative daycare services, research has not
      demonstrated an improvement in patient outcomes. This study aimed to determine
      the effect of palliative daycare on hope. METHODS: This was a prospective cohort
      study that compared three groups of patients: a daycare group and two control
      groups, one recruited before daycare opened and a matched comparison group.
      Patients were interviewed at baseline and at two follow-ups using the Herth Hope
      Index. RESULTS: In all, 22 daycare patients completed a baseline interview (T1);
      12 a second (T2); and 9 a third (T3). Corresponding numbers were: before group
      (56, 34, 24) and matched group (49, 29, 19). An independent samples t-test
      confirmed a significant difference between the groups from T1 to T2 (mean
      difference=3.20, p=0.007), with the daycare group experiencing an increase in
      hope not seen in the other groups. However, this was not maintained. CONCLUSION:
      Daycare may effect an initial improvement in hope. The study suffered from
      attrition and the sample was small. Further robust evaluation of daycare is
      needed.

PMID- 21957800
TI  - Emergency department use among end-of-life home care clients.
AB  - Emergency department (ED) use is a quality-of-care indicator for community-based
      end-of-life (EOL) care. This study examined ED use by EOL home care clients. The
      sample included all EOL home care clients who received care from one community
      care access centre in Ontario, Canada. Information on health was gathered using
      the interRAI instrument for palliative care. Data were collected between May 2009
      and January 2010. The sample included 93 home care clients. Results showed that
      35 percent of clients used the ED within 45 days of assessment. Multivariate
      analysis identified two determinants of ED use: excessive weight loss and
      previous hospitalization. Managing terminal illness is often a difficult task,
      and comprehensive, ongoing assessment of clients' changing status is critical.
      Client care and service planning for clients who have lost excessive amounts of
      weight or who have been recently hospitalized need to be monitored closely to
      prevent any future avoidable ED use.

PMID- 21957801
TI  - Nursing guidelines for end-of-life care in long-term care settings: sustainable
      improvements to care.

PMID- 21957802
TI  - Constructing a post-graduate palliative care curriculum: the Israeli National
      Palliative Care Training (INPACT) experience.

PMID- 21957803
TI  - Addressing suffering through an inter-professional online module: learning with,
      from, and about each other.

PMID- 21957804
TI  - 2008 Department of Defense (DoD) recruit oral health survey.

PMID- 21957805
TI  - Re-engineering diabetes care.

PMID- 21957806
TI  - More on in-flight emergencies.

PMID- 21957807
TI  - Perfect blend.

PMID- 21957808
TI  - Driving while low.

PMID- 21957809
TI  - A Beacon in the state.

PMID- 21957810
TI  - From doubter to believer.

PMID- 21957811
TI  - Sweet debate: do artificial sweeteners contribute to rather than combat obesity?

PMID- 21957812
TI  - Paths to a cure. Research are going down many roads in their quest to cure
      diabetes.

PMID- 21957813
TI  - Diabetes in Tanzania. A summer project offers a glimpse at the problems that
      plague the Tanzanian health care system.

PMID- 21957814
TI  - My fat ass: a miniature donkey teaches lessons on helping patients fight obesity.

PMID- 21957815
TI  - Recognizing and managing type 2 diabetes mellitus in children: an algorithm for
      primary care providers.
AB  - During the last two decades, type 2 diabetes mellitus increasingly has been seen
      in children. Although still not as common as type 1 diabetes among children, it
      has become the leading form of diabetes among adolescents of certain ethnicities.
      It is imperative that primary care providers recognize the risk factors, perform
      appropriate screening tests, and initiate therapy for children who have type 2
      diabetes or prediabetes. This article discusses the epidemiology and pathogenesis
      of the disease, complications, and treatments, and includes a concise, easy-to
      follow algorithm to assist providers in diagnosing and treating young patients.

PMID- 21957816
TI  - An overview of continuous glucose monitoring and the ambulatory glucose profile.
AB  - Managing diabetes is essentially a balancing act, as patients and physicians work
      together to control blood glucose levels to avoid the symptoms of and long-term
      organ damage caused by glucose variability--the often unpredictable fluctuations
      between levels that are too high (hyperglycemia) and too low (hypoglycemia). For
      years, self-monitoring of blood glucose levels has been the treatment standard.
      With newer technology, however, continuous blood glucose monitoring (CGM) is now
      possible. This article describes CGM, presents evidence about its efficacy, and
      outlines how visual displays of CGM data can improve clinicians' decisions about
      therapies.

PMID- 21957817
TI  - The Minnesota Partnership to Conquer Diabetes.
AB  - The University of Minnesota and Mayo Clinic have launched a 10-year effort called
      the Decade of Discovery: A Minnesota Partnership to Conquer Diabetes. The
      partnership harnesses the extensive research expertise at the two institutions in
      an effort to make discoveries that will transform prevention, management, and
      treatment of diabetes--a disease that affects one in three people in the state.
      The ultimate goal isto find a cure. This article describes the vision for this
      undertaking as well as research that might one day lead to a cure.

PMID- 21957818
TI  - The Minnesota Diabetes Plan 2015: Stemming the tide on an epidemic and improving
      patient care.
AB  - The Minnesota Diabetes Steering Committee, a group of experts in diabetes care
      and prevention from around the state, in collaboration with the Minnesota
      Department of Health, is working to slow the incidence of diabetes and improve
      the care of Minnesotans who have the disease. The steering committee has
      developed a new five-year diabetes plan for the state that identifies nine areas
      around which stakeholders will focus energy and take action. This article
      describes that plan.

PMID- 21957819
TI  - Earthquake country.

PMID- 21957820
TI  - Dentist-technician collaboration in the digital age: enhancing outcomes through
      photography, teamwork, and technology.
AB  - The cornerstone of a strong and successful dentist-technician relationship is
      communication. High-level collaboration across distances requires modern
      technology to communicate expectations, potential outcomes, and limitations.
      Carefully calibrated digital photography is an essential element in this
      inherently artistic process. This ensures a system of checks and balances to
      minimize the potential for miscommunication and remakes. Forthcoming technologies
      will allow dentist-technician teams to reach ever-greater levels of
      collaboration.

PMID- 21957821
TI  - The relationship between dentists and dental laboratories--predictions for the
      future.
AB  - This article provides an overview of the key market changes that are impacting
      the day-to-day relationship between dentists and dental laboratories and
      technicians. There are a variety of factors that facilitate the need for broader
      communication between dentists and dental technicians.

PMID- 21957822
TI  - Mucogingival surgery: where we stand today.
AB  - Mucogingival problems are developmental and acquired aberrations in the
      morphology, position, and/or the amount of gingiva surrounding teeth. According
      to an academic report by American Academy of Periodontology, mucogingival therapy
      should be advocated for gingival augmentation and to create adequate vestibular
      depth in areas with insufficient attached gingiva. This paper provides an
      overview on mucogingival surgical procedures from its inception to the current
      time.

PMID- 21957823
TI  - Failure to set a volume limit for magnesium bolus dose leads to harm.

PMID- 21957824
TI  - Saluting nurse leadership and problem-solving Nursing Week 2011: expert caring
      makes a difference.

PMID- 21957825
TI  - Elevated levels of DNA methylation at the OPRM1 promoter in blood and sperm from
      male opioid addicts.
AB  - OBJECTIVE: The OPRM1 gene was studied for DNA methylation in opioid dependence
      and possible paternal contribution to epigenetic inheritance of altered
      methylation profiles. PARTICIPANTS AND METHODS: DNA was extracted from blood and
      sperm from 13 male opioid addicts and 21 male control subjects. DNA methylation
      was determined by pyrosequencing in 24 CpG sites at the OPRM1 promoter region.
      RESULTS: The authors found significantly increased overall methylation in blood
      DNA from addicted subjects (Kruskal-Wallis [K-W] p = 0.013). Seven CpG sites
      showed significantly hypermethylated blood DNA from cases when compared with
      blood DNA from controls (p < 0.05 at CpGs 5, 9, 10, 11, 18, 23, and 24). In sperm
      derived DNA from addicts, the methylation was significantly increased at CpG 2 (p
      = 0.012), and overall methylation did not reach significant difference (K-W p =
      0.523). CONCLUSIONS: Increased DNA methylation in the OPRM1 gene is associated
      with opioid dependence. Hypermethylated CpG sites located in OPRM1 promoter may
      potentially block the binding of Sp1 and other transcription activators, thus
      leading to OPRM1 silencing. The increased DNA methylation in sperm may suggest a
      way of epigenetic heritability of opioid abuse or dependence phenotypes.

PMID- 21957826
TI  - Opioid therapy for chronic pain: physicians' attitude and current practice
      patterns.
AB  - Although opioid therapy is widely used for the treatment of chronic pain
      conditions, there is a lack of consensus on a number of practical issues related
      to the use of prescription opioids. The authors conducted a comprehensive
      practice-oriented survey to examine physicians' attitudes, knowledge, experience,
      and practice patterns regarding opioid therapy for chronic pain management. The
      survey was conducted during 2007 and 2008 through nationwide direct mails and e
      mails to physicians who are currently practicing in the United States. The survey
      contained 23 questions divided into six categories: (1) physicians' overall view
      on opioid therapy for chronic pain management; (2) clinical indications for
      opioid therapy; (3) patient-related factors influencing the decision to begin
      opioid therapy; (4) effectiveness of opioid therapy; (5) choice of opioid
      regimen; and (6) opioid agreement and opioid abuse behavior. The survey results
      suggest that opioid therapy remains as an important treatment option for chronic
      malignant and nonmalignant pain. However, the survey results should be viewed in
      the context of a low response rate (18.2 percent). These results also suggest
      that by improving the clinical knowledge of physicians participating in opioid
      therapy through education and collaboration, including a team approach with
      consultation from pain specialists, psychologists, and others, a better outcome
      for opioid therapy in patients with chronic pain conditions could be achieved.

PMID- 21957827
TI  - Analgesic treatment for moderate-to-severe acute pain in the United States:
      patients' perspectives in the Physicians Partnering Against Pain (P3) survey.
AB  - OBJECTIVES: To evaluate patients' perceptions of the adequacy of analgesia for
      moderate-to-severe acute pain and the influence of opioid-related side effects in
      outpatient pain management. SETTING: The Physicians Partnering Against Pain (P3)
      survey of analgesic treatment for moderate-to-severe acute pain in the United
      States. PATIENTS: Adults with moderate-to-severe acute pain at their first
      analgesic followup visit. MAIN OUTCOME MEASURES: Analgesic level was determined
      from the World Health Organization'spain ladder (0 = none; 1 = nonopioid; 2 =
      weak opioid; 3 = strong opioid). Pain intensity was derived from numeric rating
      scale (NRS) scores (0 = none [NRS = 0]; 1 = mild [NRS = 1-3]; 2 = moderate [NRS =
      4-7]; 3 = severe [NRS = 8-10). Pain management index scores were calculated as
      the analgesic level minus the pain intensity. Opioid recipients responded to
      questions on the P3 survey regarding side effects and their management. RESULTS:
      Of the 50,869 patients with complete data for analysis, 22,267 (44 percent) had
      received potentially inadequate analgesia, including 43, 46, and 52 percent of
      patients aged < 65, 65-74, and > or = 75 years, respectively. Of the 39,6 75
      patients treated with an opioid, 10,925 (28 percent) experienced at least one
      gastrointestinal side effect (nausea, vomiting or constipation). Many of these
      patients stopped taking the medication (13 percent) or reduced their dose (16
      percent) to manage gastrointestinal side effects. CONCLUSIONS: In the P3 study,
      one of the largest outpatient surveys conducted in pain management, moderate-to
      severe acute pain continued to be widely undertreated in outpatient settings in
      the United States, particularly among older patients. Opioids with improved
      tolerability profiles might help to alleviate this undertreatment of moderate-to
      severe acute pain.

PMID- 21957828
TI  - Economic evaluation of OROS hydromorphone for chronic pain: a Pan-European
      perspective.
AB  - OBJECTIVES: OROS hydromorphone (osmotic extended-release oral delivery system
      [OROS] hydromorphone) is a long-acting opioid analgesic, which is approved in
      Europe for the management of severe pain. The authors aimed to estimate the
      economic value of this product relative to other widely used oral opioids,
      including sustained-release morphine, extended-release (ER) oxycodone, and twice
      daily (bid) hydromorphone. DESIGN: An adaptable, decision-analytic cost-utility
      model was developed. Separate versions of the model were developed for five
      European countries: Germany, Denmark, Slovakia, Portugal, and Italy. RESULTS:
      OROS hydromorphone represents a cost-effective alternative to other strong oral
      opioids in the treatment of both nonmalignant and malignant pain in all five
      countries. In the treatment of chronic severe nonmalignant pain, OROS
      hydromorphone was dominant (ie, lower cost and incremental quality-adjusted life
      years gains) when compared with ER oxycodone in Denmark and bid hydromorphone in
      Germany. Likewise, OROS hydromorphone was dominant in the treatment of chronic
      severe malignant pain when compared with ER oxycodone in both Germany and Denmark
      and when compared with bid hydromorphone in all markets where hydromorphone was
      marketed. CONCLUSIONS: This model demonstrates the cost effectiveness of OROS
      hydromorphone relative to other strong oral opioids in the treatment of chronic
      severe malignant and nonmalignant pain.

PMID- 21957829
TI  - Effect of fentanyl buccal tablet on pain-related anxiety: a 4-week open-label
      study among opioid-tolerant patients with chronic and breakthrough pain.
AB  - OBJECTIVE: To evaluate the effect of fentanyl buccal tablet (FBT) on pain-related
      anxiety in opioid-tolerant patients with chronic pain and breakthrough pain
      (BTP). DESIGN: This study consisted of a screening visit, open-label titration
      period, and 4-week open-label treatment period. SETTING: Thirty-one US study
      centers. PATIENTS: Opioid-tolerant adults with chronic, persistent pain
      experiencing 1-4 BTP episodes per day at baseline. Two hundred eighteen patients
      were enrolled in this study; 180 completed the titration period; and 169
      completed the treatment period. INTERVENTION: Patients were treated with FBT (100
      800 microg) for BTP episodes for 4 weeks while continuing their around-the-clock
      opioid regimens. MAIN OUTCOME MEASURES: Change from baseline in the Pain Anxiety
      Symptoms Scale (PASS) total score at the final visit. RESULTS: Based on a mean
      baseline PASS total score of 82.6, study patients had a high level of anxiety; 92
      patients (42 percent) had a history of anxiety disorders. The change from
      baseline in PASS total score was not statistically significant (mean change, 
      1.6; p = 0.322). Numerical improvements were reported in some secondary measures
      (eg, Beck Depression Inventory total score /mean change, -1.1; p = 0.038) and
      categorical measures (eg, Pain Flare Treatment Satisfaction, Patient Assessment
      of Function, and Clinician Assessment of Patient Function ratings). FBT was
      generally well tolerated, with no serious adverse events related to study drug.
      CONCLUSIONS: Four weeks of treatment with FBT did not reduce anxiety to a
      clinically meaningful extent, although improvement was reported in several
      secondary measures of functioning. Further research is needed to assess the
      impact of treatment for BTP on anxiety symptoms in opioid-tolerant patients with
      BTP.

PMID- 21957830
TI  - Depressive symptoms in community-dwelling older adults receiving opioid therapy
      for chronic pain.
AB  - OBJECTIVE: The purpose of the study was to identify factors associated with
      depressive symptoms in community-dwelling older adults receiving prescription
      opioids for chronic pain. DESIGN: This was a cross-sectional research design. A
      survey was used to gather demographic information, pain severity, health status,
      and factors associated with depressive symptoms. SETTING: Eleven outpatient
      clinics affiliated with the Baltimore Veterans Affairs Medical Center and the
      University of Maryland Medical System were included. PARTICIPANTS: One hundred
      sixty-three older adults receiving opioid medications for chronic pain were
      recruited. OUTCOME MEASURES: Depressive symptoms were assessed via the Center for
      Epidemiologic Studies Depression Scale-10 (CESD-10). RESULTS: Univariate,
      bivariate, and ordinary least square (OLS) regression analyses were conducted to
      identify frequencies and to address the research questions. Nearly 40 percent of
      the elderly opioid therapy patients had depressive symptoms on the CESD-10.
      Bivariate analysis revealed that higher levels of pain severity were related to
      higher levels of depressive symptoms. OLS regression analysis revealed four risk
      factors significantly associated with higher depressive symptoms: higher pain
      severity, lower levels of functional status, lower levels of spirituality, and
      lower levels of social support. Age, gender, living alone, and perception of
      health status were not significantly associated with depressive symptoms.
      CONCLUSIONS: Depression is an underdiagnosed, treatable pain comorbidity that
      should be evaluated in older patients receiving opioid therapy. Undertreated
      depression in chronic pain patients receiving opioid medications may explain
      suboptimal improvement in pain and functional status despite increasing opioid
      dosage.

PMID- 21957832
TI  - Social accountability and dental research.

PMID- 21957831
TI  - Analgesic efficacy of intravenous naloxone for the treatment of postoperative
      pruritus: a meta-analysis.
AB  - OBJECTIVES: Pruritus may be a significant problem for patients in the
      postoperative period. There are many options for the treatment of pruritus
      including intravenous (IV) naloxone. However, it is not clear whether the use of
      IV naloxone may also affect analgesia or other opioid-related side effects. The
      authors have performed a systematic review to further examine this issue.
      METHODS: Systematic literature searches of the National Library of Medicine's
      PubMed and EMBASE databases were conducted using terms related to postoperative
      use of IV naloxone. Only randomized controlled trials comparing IV naloxone used
      either as a continuous infusion or part of an IV patient-controlled analgesia
      (PCA) regimen after surgical procedures were considered. The data on pertinent
      study characteristics and relevant outcomes were extracted from accepted
      articles. There was no restriction on language for inclusion. Meta-analysis was
      performed using the Review Manager 4.2.10 (The Cochrane Collaboration, 2004). A
      random effects model was used. RESULTS: The literature searches yielded eight
      articles that met all inclusion criteria. There were a total of 424 subjects in
      the naloxone group and 376 in the saline group. The authors found that the use of
      naloxone was associated with a decreased risk for pruritus (odds ratio [OR] =
      0.40, 95% confidence interval [CI] = 0.21-0.79, p = 0.006] and nausea [OR = 0.62,
      95% CI = 0.43-0.89, p = 0.009]. However, the use of IV naloxone (vs no naloxone)
      did not significantly influence the risk of postoperative emesis [OR = 0.97, 95%
      CI = 0.70-1.33, p = 0.83], opioid consumption [OR = 0.29, 95% CI = -3.54-4.13, p
      = 0.88], or sedation [OR = 0.82, 95% CI = 0.38-1.74, p = 0.60]. Finally, the use
      of IV naloxone did not appear to be associated with any significant change in
      visual analog score pain scores at 24 hours postoperatively (weighted mean
      difference = -0.14, 95% CI = -0.50-0.23, p = 0.46). CONCLUSIONS: Our pooled
      analysis examining the analgesic efficacy of IV naloxone (either as a continuous
      infusion or IV PCA) revealed that naloxone was associated with a decrease in
      pruritus and nausea without any increase in pain scores. When compared with
      controls, the use of IV naloxone was not associated with any significant changes
      in opioid consumption or with the risk of sedation or emesis.

PMID- 21957833
TI  - Clinical working postures of bachelor of oral health students.
AB  - OBJECTIVE: To observe and describe the clinical working postures of final-year
      Bachelor of Oral Health (BOH) students. DESIGN: Pilot observational study.
      SETTING: The University of Otago Faculty of Dentistry and School of
      Physiotherapy. METHODS: Eight final-year BOH students voluntarily participated in
      this study, where postural data were collected using a digital video camera
      during a standard clinical treatment session. The postural data were analysed
      using 3D Match biomechanical software. RESULTS: Final-year BOH students who work
      in the seated position are exposed to neck flexion of greater than 35 degrees,
      together with trunk flexion greater than 20 degrees and bilateral elbow flexion
      greater than 90 degrees. CONCLUSIONS: The findings of this study agree with the
      findings of previous postural studies of dental professionals. Dental hygiene
      students, together with their clinical supervisors, need to be aware of the
      importance of good working posture early in their careers, and pay particular
      attention to the degree of neck flexion occurring for prolonged periods.

PMID- 21957834
TI  - Further examination of the prevalence of MIH in the Wellington region.
AB  - OBJECTIVES: The aim of this study was to further investigate the prevalence of
      Molar Incisor Hypomineralisation (MIH) in the Wellington region, in order to
      expand on the findings of a recent study. DESIGN: A survey of MIH in a sample of
      7-to-10-year-old children attending primary school in Central Wellington,
      together with data from a similar survey conducted earlier in Wainuiomata.
      METHOD: Using the modified Developmental Defects of Enamel index, a single
      paediatric dentist examined students in the classroom. Any visible occurrences of
      demarcated opacities, post-eruptive breakdown of enamel and hypoplasia were
      recorded, along with dental caries experience in primary and permanent teeth. The
      data were combined with those from the previous study, and statistical analysis
      was undertaken using the combined data-set. RESULTS: In the Central Wellington
      study, examinations were conducted on 235 children (participation rate 58.8%,
      mean age 8.2 years). MIH prevalence was 18.8%. Demarcated opacities and post
      eruptive breakdown affected 23.9% and 8.1% (respectively) of the sample. Pooling
      the data from Central Wellington and Wainuiomata gave a total sample of 756 (mean
      age 8.2), among which MIH prevalence was 15.7%. Demarcated opacities and post
      eruptive breakdown (of any tooth) affected 18.0% and 4.6%, respectively.
      Hypoplasia of any tooth was observed in 0.7% of the pooled sample. There was no
      statistically significant association between MIH and either ethnicity or school
      decile. Although MIH prevalence was 3.9 percentage points higher in the Central
      Wellington schools than in Wainuiomata, socioeconomic status (measured through
      school decile) was not significantly associated with MIH. The presence of
      developmental defects of enamel was associated with greater caries experience in
      the permanent dentition. CONCLUSIONS: In the Wellington schools involved in the
      study, approximately one in six 7-10-year-old children had MIH. Neither school
      decile nor ethnicity were modifying factors in the occurrence of MIH.

PMID- 21957835
TI  - Undergraduate dental education in New Zealand: 2007-2009 final-year student
      feedback on clinical learning environments.
AB  - Dental education is a unique form of health professional education. This is
      because the clinical training component largely occurs within the dental school
      and involves students carrying out irreversible patient interventions early in
      their education. Perhaps not surprisingly, previous research indicates that
      dental education (and particularly the clinical component) is stressful for many
      students. In their responses to an annual clinical learning environment survey,
      final-year Bachelor of Dental Surgery (BDS) students at the University of Otago
      have suggested that teaching staff play a key role in mitigating or compounding
      stressors associated with students' clinical work. In 2007-2009 questionnaire
      responses, students identified the kinds of staff feedback which they found
      constructive or unhelpful while working in patient clinic settings, described
      their responses to feedback received, and identified ways in which students'
      clinical learning experiences might be improved. This paper outlines 2007-2009
      University of Otago Faculty of Dentistry clinical learning environment survey
      findings, and relates these to the literature on effective teaching and clinical
      teaching. It then describes programmatic changes and research initiatives
      developed in response to student feedback.

PMID- 21957836
TI  - Dental caries in Taranaki adolescents: a cohort study.
AB  - OBJECTIVE: To document changes in disease experience among Taranaki adolescents
      in order to enhance understanding of the natural history of dental caries in a
      key developmental period. METHOD: A random sample of 430 adolescents first
      examined in 2003 at age 13 were re-examined at age 16, when 255 (59.3%) took
      part. Dental caries status (in the permanent dentition) was recorded at each age
      by a single calibrated examiner following World Health Organization guidelines.
      The age-13 and 16 data-sets were merged once clinical data collection was
      completed. Caries increment was determined by comparing the baseline and follow
      up status of each surface. RESULTS: Caries prevalence (1+ DMFS) rose from 68% to
      79%; mean DMFS rose from 2.9 (SD 4.7) to 3.6 (SD 4.8), and the prevalence of high
      caries experience (5+ DMFS) rose from 20% to 41%. The 3-year mean net caries
      increment of 0.5 surfaces (SD 2.6) was dominated by occlusal surfaces and the
      overall incidence of caries was approximately 46%. Over one-third of the cohort
      (37%) presented with decayed surfaces at follow-up, and this was significantly
      higher among Maori and males. CONCLUSION: New Zealand adolescents still appear to
      be experiencing caries at a considerable rate, with social and ethnic
      inequalities plainly apparent (and appearing to widen).

PMID- 21957837
TI  - Bisphosphonate-associated osteonecrosis of the jaw: a six-year history of a case.
AB  - Patients with multiple myeloma are usually treated with IV bisphosphonates soon
      after diagnosis. Bisphosphonate administration has been associated with
      bisphosphonate-associated osteonecrosis of the jaw (BONJ). BONJ can occur
      spontaneously; the most common spontaneous site is at the lingual aspect of the
      posterior mandible. The condition can continue to expose more bone well after
      bisphosphonates have been discontinued. This report describes the development and
      progression of a spontaneous BONJ of the mandible in an individual with multiple
      myeloma. The area of exposed bone slowly increased in size and eventually became
      mobile. Removal of the sequestrum provided a temporary respite from exposed bone
      and resolution of symptoms, but there was a recurrence of exposed bone that
      required further sequestrum removal.

PMID- 21957838
TI  - Full-arch milled titanium implant bridge: technical report.
AB  - The manufacturing of full-arch fixed implant-supported bridges with the use of
      the traditional lost wax technique remains a technical challenge. Distortion of
      the alloy during casting and subsequent heating cycles during porcelain build-up
      causes numerous problems. Fracturing of porcelain on large restorations is
      difficult and costly to restore. The fitting problems can be eliminated by
      utilising CAD/CAM technology in the manufacturing of long-span or full-arch
      titanium bridges. Repair of damaged porcelain can be simplified with the use of
      discrete, individually-removable crowns on the bridge.

PMID- 21957839
TI  - Respect needed for RNs who make the "Michigan Difference" at U of M hospitals.

PMID- 21957840
TI  - A Main Street contract for the American people. Learning what National Nurses
      United is all about.

PMID- 21957841
TI  - Looking forward at primary care.

PMID- 21957842
TI  - Primary care must evolve to survive.

PMID- 21957843
TI  - Incomplete medical record release authorization?

PMID- 21957844
TI  - Of primary concern: challenges and possible solutions to Tennessee's PCP
      shortage.

PMID- 21957845
TI  - Primary care through the looking glass.

PMID- 21957846
TI  - Revitalizing primary care resident education with outpatient team-based care.

PMID- 21957847
TI  - TMA membership issues, part II.

PMID- 21957848
TI  - Alternative models for medical practice innovation.

PMID- 21957849
TI  - Prescribers, is the relationship with your "authorized agent" explicit,
      transparent and proper?

PMID- 21957850
TI  - Peri-adrenal hemangioma mimicking a pheochromocytoma on metaiodobenzylguanidine
      (MIBG) scan.
AB  - Pheochromocytomas account for less than one percent of hypertension and are
      usually suspected because of clinical manifestations, confirmed by laboratory
      evaluation and subsequently localized by radiology. Higher HU units on pre
      contrast CT and hyperintense signal on T2 weighted MRI images are often seen in
      pheochromocytoma. Metaiodobenzylguanidine (MIBG) scans have been widely used to
      localize pheochromocytoma and false-positive scans are reported to be rare. We
      report a hypertensive patient with symptoms consistent with a pheochromocytoma,
      with a left adrenal mass with a pre-contrast HU of 8 but a 70 HU post-contrast
      value. No biochemical evidence of catecholamine excess was noted. A MIBG scan was
      reported as highly suspicious for a pheochromocytoma. Laparoscopic resection of
      the mass confirmed the presence of a peri-adrenal hemangioma with both capillary
      and cavernous components. We postulate that the accumulation of MIBG because of
      the hemangioma was responsible for the false-positive MIBG scan.

PMID- 21957852
TI  - The unique bis-(disulfato)-aurate anion [Au(S2O7)2](-): synthesis and
      characterization of Li[Au(S2O7)2] and Na[Au(S2O7)2)].
AB  - The reaction of Au(OH)(3) and oleum (65% SO(3)) in the presence of M(2)SO(4) (M =
      Li, Na) afforded yellow single crystals of Li[Au(S(2)O(7))(2)] (triclinic, P 1, Z
      = 1, a = 532.20(3), b = 649.69(4), c = 836.72(5) pm, alpha = 107.982(2) degrees ,
      beta = 90.171(2) degrees , gamma = 102.583(2) degrees , V = 267.80(3) A(3)) and
      Na[Au(S(2)O(7))(2)] (monoclinic, P2(1)/n, Z = 2, a = 533.31(3), b = 1193.38(7), c
      = 907.67(5) pm, beta = 98.548(3) degrees , V = 571.26(6) A(3)). Both compounds
      exhibit the unprecedented [Au(S(2)O(7))(2)](-) anion in which a square planar
      coordination of the central gold atom is achieved by the chelating attachment of
      two disulfate groups. The disulfates were characterized by means of IR
      spectroscopy and DTA/TG measurements. For both compounds, the decomposition
      occurs via several steps and is finished at about 450  degrees C at the stage of
      elemental gold and the sulfates M(2)SO(4) (M = Li, Na), as revealed by X-ray
      powder diffraction of the residues.

PMID- 21957853
TI  - Introduction to the special issue on "LGBTQ campus experiences".

PMID- 21957854
TI  - "Our college is changing": women's college student affairs administrators and
      transgender students.
AB  - Student affairs administrators at contemporary American women's colleges are
      charged with supporting the personal, intellectual, and relational growth of
      students. A small but vocal group of students who identify as transgender and who
      are living as male, genderqueer, or transitioning to live as male, have emerged
      as a visible subpopulation in highly selective women's colleges. In this
      qualitative, phenomenological study of the perceptions of student affairs
      administrators (n = 31), three participant profiles-ambivalent, supporter, and
      advocate-emerged. Implications for student affairs practice, theory, and the
      continued transformation of educational environments in support of transgender
      students are discussed.

PMID- 21957855
TI  - Disclosure as an interaction: why lesbian athletes disclose their sexual
      identities in intercollegiate sport.
AB  - Over the years, the number of gay, bisexual, and lesbian athletes who have
      disclosed their sexual identities has been increasing. Given that sport has
      traditionally been defined as a heterosexist institution, this pattern is
      deserving of attention and investigation ( Anderson, 2001 ). In response, the
      present study examines why intercollegiate lesbian athletes disclose their sexual
      identities in the sport context. In-depth interviews were conducted with 16 self
      identified lesbian athletes who disclosed their sexual identities while
      participating in intercollegiate sport. Unlike most past literature on
      disclosure, the present study approaches disclosure as an interactional process
      that involves a discloser, an audience, and a context.

PMID- 21957856
TI  - Understanding Asian/american gay, lesbian, and bisexual experiences from a
      poststructural perspective.
AB  - This study explores the college experiences of nine Asian/American gay, lesbian,
      and bisexual students and, specifically, the impact of concealing or revealing
      their sexual orientation on their emerging sense of self. By utilizing a
      Foucauldian, poststructural theoretical perspective, the researcher found that
      the students navigated multiple discourses, and their decisions about revealing
      their sexual orientation were based on relationships formed within those
      discourses. These decisions, in turn, helped many of the students grasp their
      emerging agency within the dominant discourse. To conclude, the researcher
      discusses the implications of these findings for higher education as a whole.

PMID- 21957857
TI  - Negotiating multiple identities: how African-American gay and bisexual men
      persist at a predominantly White institution.
AB  - This consensual qualitative research (CQR) study explores factors contributing to
      the persistence of African-American gay and bisexual men at a predominately White
      institution (PWI). Eight participants consistently noted that involvement with an
      African-American community was crucial to navigating the challenges of attending
      a PWI. Participants reported that their racial identity was more salient than
      their sexual orientation in creating social support, and they described feeling
      uncomfortable using lesbian, gay, bisexual, and transgender (LGBT) resources.
      Implications, including education about sexual orientation within African
      American campus communities, LGBT outreach to communities of color, and continued
      institutional support for African-American campus organizations, are discussed.

PMID- 21957858
TI  - Sexual orientation and differences in mental health, stress, and academic
      performance in a national sample of U.S. college students.
AB  - This study examined the relationships of mental health issues and sexual
      orientation in a national sample of college students. Using the Fall 2009
      American College Health Association-National College Health Assessment, responses
      from heterosexual, gay, lesbian, bisexual, and unsure students (N = 27,454)
      relating to mental health issues and impact of these issues on academics were
      examined. The findings indicate that gay, lesbian, bisexual, and unsure students
      consistently reported higher levels of mental health issues and a more frequent
      impact on academics because of these issues than heterosexual students. Bisexuals
      frequently reported higher levels than students identifying as gay, lesbian, and
      unsure.

PMID- 21957859
TI  - A qualitative analysis of faculty advocacy on LGBT issues on campus.
AB  - Faculty activism is an integral part of shared governance in higher education
      institutions, yet little is known about the dynamics that underlie this activism.
      Using oral history interviews with 30 faculty members working to secure lesbian,
      gay, bisexual, and transgender (LGBT)-supportive policies on their respective
      campuses, this article identifies reasons the faculty members became involved in
      this advocacy, types of advocacy in which they engaged, factors associated with
      engaging in advocacy, and challenges facing these faculty advocates. Specific
      dynamics facing LGBT faculty are discussed, and predictions are made for the
      future of faculty advocacy on LGBT campus policy issues.

PMID- 21957860
TI  - Structuring injustice: partisan politics in the making and unmaking of James
      Madison University's equal opportunity policy.
AB  - This analysis contributes to LGBT campus climate research on the quality of
      campus life in higher education in the United States. We argue that public
      education institutions in different states face divergent impediments to
      improving campus climate, and that more research is needed identifying structural
      factors affecting campus climate. Using a social systems analysis of policymaking
      at one university as a case study, we illustrate how partisan politics and state
      regulation make Virginia colleges and universities more vulnerable to political
      scrutiny and control. Finally, we propose a social justice-oriented policy agenda
      to address structural inequalities.

PMID- 21957861
TI  - Assessing LGBTQ campus climate and creating change.
AB  - We report the findings of a climate study of a liberal arts college in
      Pennsylvania. This climate assessment was comprehensive in content (heterosexual
      and cisgender individuals' attitudes, and LGBTQ individuals' experiences),
      participants (faculty, staff, and students), and methodology (qualitative and
      quantitative). We found low levels of sexual prejudice and generally positive
      perceptions of the campus, but positive attitudes were more strongly endorsed by
      heterosexual and cisgender than LGBTQ participants. We consider the impact of
      these perceptions on LGBTQ students' co-curricular involvement and discuss the
      institutional changes that are underway as a result of our study.

PMID- 21957862
TI  - Dendrimer-induced leukocyte procoagulant activity depends on particle size and
      surface charge.
AB  - AIMS: Thrombogenicity associated with the induction of leukocyte procoagulant
      activity (PCA) is a common complication in sepsis and cancer. Since nanoparticles
      are increasingly used for drug delivery, their interaction with coagulation
      systems is an important part of the safety assessment. The purpose of this study
      was to investigate the effects of nanoparticle physicochemical properties on
      leukocyte PCA, and to get insight into the mechanism of PCA induction. MATERIALS
      & METHODS: A total of 12 formulations of polyamidoamine (PAMAM) dendrimers,
      varying in size and surface charge, were studied in vitro using recalcification
      time assay. RESULTS: Irrespective of their size, anionic and neutral dendrimers
      did not induce leukocyte PCA in vitro. Cationic particles induced PCA in a size-
      and charge-dependent manner. The mechanism of PCA induction was similar to that
      of doxorubicin. Cationic dendrimers were also found to exacerbate endotoxin
      induced PCA. CONCLUSION: PAMAM dendrimer-induced leukocyte PCA depends on
      particle size, charge and density of surface groups.

PMID- 21957863
TI  - Can leptin-derived sequence-modified nanoparticles be suitable tools for brain
      delivery?
AB  - AIM: In order to increase the knowledge on the use of nanoparticles (NPs) in
      brain targeting, this article describes the conjugation of the sequence 12-32
      (g21) of leptin to poly-lactide-co-glycolide NPs. The capability of these
      modified NPs to reach the brain was evaluated in rats after intravenous
      administration. MATERIALS & METHODS: The g21 was linked on the surface of NPs
      labeled with tetramethylrhodamine by means of the Avidin-Biotin technology. The
      g21-labeled NPs were injected into the tail vein of rats and, after animal
      sacrifice, the brain localization was evaluated by confocal microscopy,
      fluorescence microscopy and electron microscopy. Studies to evaluate the
      biodistribution of the g21-modified NPs in comparison to the unmodified NPs were
      also carried out. Moreover, to confirm the absence of any anorectic effect of g21
      linked on the surface of NPs, appropriate studies were used to assess the rats.
      RESULTS: After intravenous administration, the g21-modified NPs were able to
      cross the blood-brain barrier and to enter the brain parenchyma. The
      biodistribution studies of both unmodified and modified NPs pointed out an uptake
      at liver and spleen level, whereas only the g21-modified NPs showed brain
      localization. The food-intake experiments pointed out that the intravenous
      administration of g21 conjugated to the NP surface did not produce any anorectic
      effect in the rats. CONCLUSION: g21-modified NPs were able to cross the blood
      brain barrier. These new modified NPs could be effectively considered as useful
      carrier systems for brain drug delivery.

PMID- 21957864
TI  - Caregiver perceptions of accomplishment from assisting people with multiple
      sclerosis.
AB  - OBJECTIVES: Identify factors of informal caregivers, caregiving, and people with
      multiple sclerosis (MS) receiving assistance that are associated with perceptions
      of caregiver accomplishment. METHODS: National data were collected in a telephone
      interview survey of 530 informal caregivers and analyzed using an ordered
      logistic regression model to identify factors associated with perceptions of
      caregiver accomplishment among 442 of these informal caregivers (caregivers
      providing all data in their survey responses needed for the regression model).
      RESULTS: We found that age of the person with MS and duration of caregiving
      measured by the number of hours per week the caregiver assisted the person with
      MS were significantly linked to positive perceptions of accomplishment.
      Conversely, the caregiver's perception that assisting the person with MS was
      emotionally draining, a spousal relationship, and caregiver education levels were
      significantly associated with negative perceptions of accomplishment.
      CONCLUSIONS: Health professionals treating people with MS and their caregivers
      should be sensitive to the impact caregiving has on the emotional needs of
      caregivers and to the unique support needs of spousal caregivers. Health
      practitioners also should be sensitive to the variety of benefit-finding themes
      expressed by caregivers to facilitate the caregivers' efforts to discover gains
      in their experiences assisting people with MS, such as perceptions that
      caregiving provides a sense of accomplishment.

PMID- 21957865
TI  - Trifluoroacetic acid-promoted synthesis of 3-hydroxy, 3-amino and spirooxindoles
      from alpha-keto-N-anilides.
AB  - Ketoanilides containing alkyl side chains were readily cyclized to 3-hydroxy-2
      oxindoles or spirooxindoles by a single or double intramolecular Friedel-Crafts
      reaction in the presence of trifluoroacetic acid (TFA) at room temperature or at
      45  degrees C. alpha-Iminocarboxamides, generated in situ from ketoamides,
      cyclized similarly to 3-aminooxindoles under identical conditions.

PMID- 21957866
TI  - Computerized analysis of error patterns in digit span recall.
AB  - We analyzed error patterns during digit span (DS) testing in four experiments. In
      Experiment 1, error patterns analyzed from a community sample of 427 subjects
      revealed strong primacy and recency effects. Subjects with shorter DSs showed an
      increased incidence of transposition errors in comparison with other error types
      and a greater incidence of multiple errors on incorrect trials. Experiment 2
      investigated 46 young subjects in three test sessions. The results replicated
      those of Experiment 1 and demonstrated that error patterns of individual subjects
      were consistent across repeated test administrations. Experiment 3 investigated
      40 subjects from Experiment 2 who feigned symptoms of traumatic brain injury
      (TBI) with 80% of malingering subjects producing digit spans in the abnormal
      range. A digit span malingering index (DSMI) was developed to detect atypical
      error patterns in malingering subjects. Overall, 59% of malingering subjects with
      abnormal digit spans showed DSMIs in the abnormal range and DSMI values
      correlated significantly with the magnitude of malingering. Experiment 4 compared
      29 patients with TBI with a new group of 38 control subjects. The TBI group
      showed significant reductions in digit span. Overall, 32% of the TBI patients
      showed DS abnormalities and 11% showed abnormal DSMIs. Computerized error-pattern
      analysis improves the sensitivity of DS assessment and can assist in the
      detection of malingering.

PMID- 21957867
TI  - The ecological validity of the Rey-Osterrieth Complex Figure: predicting everyday
      problems in children with neuropsychological disorders.
AB  - Despite its extensive use, the validity of the Rey Complex Figure in predicting
      everyday behavioral executive dysfunction displayed by children with various
      neuropsychological disorders is unknown. The copied figures of 263 children aged
      6 to 17 years were rescored using an accuracy approach that measured visuospatial
      ability and three process approaches developed to measure executive functioning.
      Controlling for age and IQ, partial correlations between scores derived by all
      scoring methods and the parent ratings on an executive function inventory were
      zero. In contrast, all four scoring approaches were associated with parent
      ratings on questionnaires that indexed children's academic achievement,
      developmental status, and adaptive ability. The findings suggest that the
      ecological validity of the Rey Complex Figure for children with various central
      nervous system disorders is more associated with visual-motor integration skills
      than executive functioning.

PMID- 21957868
TI  - Delays in starting antiretroviral therapy in patients with HIV-associated
      tuberculosis accessing non-integrated clinical services in a South African
      township.
AB  - BACKGROUND: Delays in the initiation of antiretroviral therapy (ART) in patients
      with HIV-associated tuberculosis (TB) are associated with increased mortality
      risk. We examined the timing of ART among patients receiving care provided by non
      integrated TB and ART services in Cape Town, South Africa. METHODS: In an
      observational cohort study, we determined the overall time delay between starting
      treatment for TB and starting ART in patients treated in Gugulethu township
      between 2002 and 2008. For patients referred from TB clinics to the separate ART
      clinic, we quantified and identified risk factors associated with the two
      component delays between starting TB treatment, enrolment in the ART clinic and
      subsequent initiation of ART. RESULTS: Among 893 TB patients studied (median CD4
      count, 81 cells/MUL), the delay between starting TB treatment and starting ART
      was prolonged (median, 95 days; IQR = 49-155). Delays were shorter in more recent
      calendar periods and among those with lower CD4 cell counts. However, the median
      delay was almost three-fold longer for patients referred from separate TB clinics
      compared to patients whose TB was diagnosed in the ART clinic (116 days versus 41
      days, respectively; P < 0.001). In the most recent calendar period, the
      proportions of patients with CD4 cell counts < 50 cells/MUL who started ART
      within 4 weeks of TB diagnosis were 11.1% for patients referred from TB clinics
      compared to 54.6% of patients with TB diagnosed in the ART service (P < 0.001).
      CONCLUSIONS: Delays in starting ART were prolonged, especially for patients
      referred from separate TB clinics. Non-integration of TB and ART services is
      likely to be a substantial obstacle to timely initiation of ART.

PMID- 21957869
TI  - Laboratory demonstration of a prozone-like effect in HRP2-detecting malaria rapid
      diagnostic tests: implications for clinical management.
AB  - BACKGROUND: Malaria rapid diagnostic tests (RDTs) are now widely used for prompt
      on-site diagnosis in remote endemic areas where reliable microscopy is absent.
      Aberrant results, whereby negative test results occur at high parasite densities,
      have been variously reported for over a decade and have led to questions
      regarding the reliability of the tests in clinical use. METHODS: In the first
      trial, serial dilutions of recombinant HRP2 antigen were tested on an HRP2
      detectiing RDT. In a second trial, serial dilutions of culture-derived Plasmodium
      falciparum parasites were tested against three HRP2-detecting RDTs. RESULTS: A
      prozone-like effect occurred in RDTs at a high concentration of the target
      antigen, histidine-rich protein-2 (above 15,000 ng/ml), a level that corresponds
      to more than 312000 parasites per MUL. Similar results were noted on three RDT
      products using dilutions of cultured parasites up to a parasite density of 25%.
      While reduced line intensity was observed, no false negative results occurred.
      CONCLUSIONS: These results suggest that false-negative malaria RDT results will
      rarely occur due to a prozone-like effect in high-density infections, and other
      causes are more likely. However, RDT line intensity is poorly indicative of
      parasite density in high-density infections and RDTs should, therefore, not be
      considered quantitative. Immediate management of suspected severe malaria should
      rely on clinical assessment or microscopy. Evaluation against high concentrations
      of antigen should be considered in malaria RDT product development and lot
      release testing, to ensure that very weak or false negative results will not
      occur at antigen concentrations that might be seen clinically.

PMID- 21957870
TI  - NIR-to-NIR two-photon excited CaF2:Tm3+,Yb3+ nanoparticles: multifunctional
      nanoprobes for highly penetrating fluorescence bio-imaging.
AB  - In this study, we report on the remarkable two-photon excited fluorescence
      efficiency in the "biological window" of CaF(2):Tm(3+),Yb(3+) nanoparticles. On
      the basis of the strong Tm(3+) ion emission (at around 800 nm), tissue
      penetration depths as large as 2 mm have been demonstrated, which are more than 4
      times those achievable based on the visible emissions in comparable
      CaF(2):Er(3+),Yb(3+) nanoparticles. The outstanding penetration depth, together
      with the fluorescence thermal sensitivity demonstrated here, makes
      CaF(2):Tm(3+),Yb(3+) nanoparticles ideal candidates as multifunctional nanoprobes
      for high contrast and highly penetrating in vivo fluorescence imaging
      applications.

PMID- 21957871
TI  - Decreased expression of transient receptor potential channels in cerebral
      vascular tissue from patients after hypertensive intracerebral hemorrhage.
AB  - Recent data indicate that transient receptor potential (TRP) cation channels play
      an important role in hypertension. Now, we tested the hypothesis that TRP
      expression is altered in human cerebral vascular tissue in patients who had
      experienced hypertensive intracerebral hemorrhage. TRPC1, TRPC3, TRPC5, TRPC6,
      TRPM4, TRPM6, and TRPM7 channels were detected in cerebral vascular tissue by
      quantitative real-time RT-PCR. Control cerebral vascular tissue was obtained from
      normotensive patients who underwent neurosurgical operation because of brain
      tumor. To examine a possible relation between the expression of TRP expression
      and hypoxic conditions caused by the intracerebral bleeding, we examined the
      expression of hypoxia inducible factor 1a (HIF1a). Transcripts of TRPC3, TRPC5,
      TRPM6, and HIF1a were significantly reduced in cerebral vascular tissue from
      patients after hypertensive intracerebral hemorrhage compared to controls. TRPC3
      mRNA correlated well with the expression of HIF1a mRNA (r(2) = 0.59; p = 0.01).
      TRPC3 expression is associated with hypertension and hypoxic conditions in human
      cerebral vascular tissue.

PMID- 21957873
TI  - Detection of hepatitis E virus RNA in plasma mini-pools from blood donors in
      England.

PMID- 21957872
TI  - TNFalpha suppresses IFNgamma-induced MHC class II expression on retinal pigmented
      epithelial cells cultures.
AB  - PURPOSE: One major consequence of retinal pigment epithelium (RPE) cell
      activation during autoimmune uveitis is the induction of MHC II molecules
      expression at their surface. IFNgamma is regarded as the main cytokine involved
      in this induction. As TNFalpha plays a central role in autoimmune uveitis, we
      investigated its effects on IFNgamma-mediated MHC II induction on RPE cells.
      METHODS: Retinal pigment epithelium cells (ARPE-19) were stimulated with
      IFNgamma, TNFalpha and the anti-TNFalpha antibody infliximab. The expression of
      MHCII and ICAM-1 was analysed by flow cytometry. The activation and expression of
      IRF-1 and STAT-1, two proteins involved in IFNgamma-signalling pathway, were
      analysed by WB. Class II transactivator (CIITA) expression was monitored by qRT
      PCR and immunoprecipitation. RESULTS: TNFalpha inhibits IFNgamma-induced MHC II
      expression on ARPE cells in a dose-dependent manner. Infliximab completely
      reverses the inhibitory effect of TNFalpha. We did not observe an inhibitory
      effect of TNFalpha on the expression of ICAM-1 induced by IFNgamma. Similarly,
      IFNgamma-induced STAT1 phosphorylation and IRF1 expression were not affected by
      TNFalpha. On the contrary, we found that TNFalpha suppresses IFNgamma-induced
      CIITA mRNA accumulation and protein expression. CONCLUSION: TNFalpha inhibits
      IFNgamma-induced MHC II expression in RPE cells. This inhibitory effect was
      reversed by infliximab and was not because of a global inhibition of IFNgamma 
      mediated RPE cell activation but rather to a specific down-regulation of CIITA
      expression. Those findings are consistent with the role of TNFalpha in the
      resolution of inflammation and might help to elucidate the complex development of
      autoimmune uveitis.

PMID- 21957874
TI  - First and second meal effects of pulses on blood glucose, appetite, and food
      intake at a later meal.
AB  - Pulses are low-glycemic appetite-suppressing foods, but it is not known whether
      these properties persist after being consumed as part of a meal and after a
      second meal. The objective of this study was to determine the effects of a fixed
      size pulse meal on appetite and blood glucose (BG) before and after an ad libitum
      test meal (pizza) and on food intake (FI) at the test meal. Males (n = 25; 21.3
      +/- 0.5 years; 21.6 +/- 0.3 kg.m(-2)) randomly consumed 4 isocaloric meals:
      chickpea; lentil; yellow split pea; and macaroni and cheese (control).
      Commercially available canned pulses provided 250 kcal, and were consumed with
      macaroni and tomato sauce. FI was measured at a pizza meal 260 min after
      consumption of the isocaloric meal. BG and appetite were measured from 0 to 340
      min. The lentil and yellow pea, but not chickpea, treatments led to lower
      appetite ratings during the 260 min prepizza meal period, and less FI at the
      pizza meal, compared with macaroni and cheese (p < 0.05). All pulse treatments
      lowered BG immediately following consumption (at 20 min) (p < 0.05), but there
      was no effect of treatment on prepizza meal BG AUC (p = 0.07). Immediately after
      the pizza meal, BG was lower following the chickpea and lentil treatments, but
      not the yellow pea treatment (p < 0.05). Postpizza meal BG AUC was lower
      following the chickpea and lentil treatments than in the yellow pea treatment (p
      < 0.05). The beneficial effects of consuming a pulse meal on appetite, FI at a
      later meal, and the BG response to a later meal are dependent on pulse type.

PMID- 21957875
TI  - Diffusion and aggregation of sodium fluorescein in aqueous solutions.
AB  - The diffusion and aggregation of sodium fluorescein in aqueous solutions was
      investigated adopting density functional theory (DFT) and molecular dynamics (MD)
      simulations. First, DFT calculations in implicit water were used to determine
      minimum energy structure and atomic charges of the solute, which were then used
      as input for explicit water MD simulations. The self-diffusion coefficient of
      sodium fluorescein was calculated using the Einstein equation, computing the mean
      square displacement from 24 ns trajectories. The calculated diffusion
      coefficient, 0.42 . 10(-5) cm(2) s(-1), is in good agreement with literature
      experimental data. The simulations confirmed the tendency of fluorescein to form
      dimers. In order to achieve a deeper understanding of aggregation phenomena, the
      dimer geometry was investigated through DFT calculations both in vacuo and in
      implicit water using different functionals and solvation theories. The results
      showed that dimerization does not occur in vacuo, as charge repulsion dominates,
      and that the minimum energy dimer structure is symmetric and stabilized by edge
      to-face pi-pi interactions. The interaction energy was computed both at the DFT
      level and through MD simulations using Umbrella Sampling. The free interaction
      energy calculated with the WHAM and Umbrella Integration protocol, -1.3 kcal/mol,
      is in good agreement with experimental data, while the value determined using DFT
      calculations is significantly smaller and depends largely from the chosen
      functional and the computational methodology used to determine the solute-solvent
      boundary surface.

PMID- 21957876
TI  - Association of vaginal delivery efforts with retinal disease in women with type I
      diabetes.
AB  - OBJECTIVE: To determine whether the second stage of labor affects the progression
      of retinopathy in women with type I diabetes mellitus (DM). RESEARCH AND DESIGN:
      The study is a secondary analysis of 192 pregnant women with type I DM who
      participated in an interdisciplinary diabetes in pregnancy intervention program
      between 1978 and 1993. Evaluation for diabetic retinopathy (DR) was performed
      each trimester and 6-12 weeks postpartum by the same two ophthalmologists. Women
      were divided into three groups: (i) elective cesarean delivery (n = 60), (ii)
      cesarean delivery prior to the second stage of labor (n = 69) and (iii) vaginal
      or cesarean delivery in the second stage (n = 63). Progression of DR during
      pregnancy and between pregnancy and postpartum was compared among the groups.
      RESULTS: Maternal demographics, glycemic control and pregnancy complications were
      similar among groups. Progression of retinopathy from early and late pregnancy to
      postpartum did not differ between the three groups. CONCLUSION: With close follow
      up and good glycemic control, expulsive efforts in the second stage of labor do
      not affect the progression of retinopathy in women with type I DM. Our data
      support the premise that pregnant women with type I DM and stable retinopathy
      should not be denied vaginal delivery, if otherwise not contraindicated.

PMID- 21957877
TI  - X-ray fluorescence elemental mapping and microscopy to follow hepatic disposition
      of a Gd-based magnetic resonance imaging contrast agent.
AB  - 1. Spatially resolved X-ray fluorescence (XRF) spectroscopy with synchrotron
      radiation is a technique that allows imaging and quantification of chemical
      elements in biological specimens with high sensitivity. In the present study, we
      applied XRF techniques at a macro and micro level to carry out drug distribution
      studies on ex vivo models to confirm the hepatobiliary disposition of the Gd
      based magnetic resonance imaging contrast agent B22956/1. 2. Gd presence was
      selectively quantified allowing the determination of the time dependent
      disappearance of the drug from blood and its hepatic accumulation in mice after
      administration. Elemental mapping highlighted the drug distribution differences
      between healthy and diseased livers. XRF microanalyses showed that in CCl(4) 
      induced hepatitis, B22956/1 has greatly reduced hepatic accumulation, shown as a
      20-fold reduction of Gd presence. Furthermore, a significant increase of Fe
      presence was found in steatotic compared with healthy livers, in line with the
      disease features. 3. The present results show that XRF might be useful in
      preclinical pharmacological studies with drugs containing exogenous elements.
      Furthermore, quantitative and high-sensitivity elemental mapping allows
      simultaneous detection of chemical variation, showing pathological conditions.
      This approach was useful in suggesting reduced B22956/1 accumulation in steatotic
      livers, thus opening possible new diagnostic perspectives for this drug.

PMID- 21957878
TI  - Sleep and the city. Abstracts of Sleep DownUnder 2011, the 23rd Annual Scientific
      Meeting of the Australasian Sleep Association and Australasian Sleep
      Technologists Association. Sydney, Australia. October 27-29, 2011.

PMID- 21957879
TI  - Skeletal status and body composition in young women with functional hypothalamic
      amenorrhea.
AB  - CONTEXT: Functional hypothalamic amenorrhea (FHA) related to hypoestrogenism and
      hormonal status may influence skeletal homeostasis and body composition. The
      study aimed to evaluate hormones concentrations, body composition and bone
      strength in FHA cases. PATIENTS AND METHODS: Total body scans using DXA method
      (DPX-L, GE Lunar) were performed in a group of 27 women aged 21.8 years +/- 3.9
      with FHA related to weight loss. References of healthy control subjects were used
      to calculate Z-scores (age and gender matched), SD-scores (height and gender
      matched), and SDs-scores (weight and gender matched). Whole skeleton bone mineral
      content (TBBMC, g) and density (TBBMD, g/cm(2)), lumbar spine (L2-L4) bone
      mineral density (SBMD; g/cm(2)), lean body mass (LBM, g) and fat mass (FM, g)
      were investigated. Relative bone strength index was calculated as the TBBMC/LBM
      ratio. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH),
      estradiol, testosterone, and prolactin (PRL) concentrations were assayed to
      characterize hormonal profile of FHA cases. RESULTS: Hormonal evaluation in
      patients with FHA revealed significantly decreased serum concentrations of
      gonadotropins and estradiol. Serum LH concentrations were 1.47 +/- 0.89 mIU/ml,
      FSH 4.44 +/- 1.94 mIU/ml. Estradiol concentrations in serum were 27.08 +/- 13.10
      pg/ml. As evidenced by Z-scores, FHA cases had decreased SBMD, TBBMD and TBBMC Z
      scores of -1.23 +/- 0.90 (p < 0.0001), -0.72 +/- 0.86 (p < 0.001), and -0.90 +/-
      1.40 (p < 0.01), respectively. Reduced FM, LBM and FM/LBM ratio Z-scores of -1.80
      +/- 2.28 (p < 0.001), -0.59 +/- 1.49 (p < 0.05) and -0.74 +/- 1.55 (p < 0.05),
      but not TBBMC/LBM Z-score of -0.54 +/- 2.14 (ns) were noted in FHA cases compared
      with healthy control cases. TBBMC, TBBMD, TBBMC/LBM when BH- or BW-matched were
      normal as evidenced by SD-scores and SDs-scores. SBMD remained reduced when BH
      matched (SD-score = -0.40 +/- 0.86; p < 0.05) whereas FM and FM/LBM were lower
      than expected in healthy, both compared to BH- and BW-dependent references. The
      length of amenorrhea in months negatively correlated with SBMD Z-score (R = 
      0.39, p < 0.05), and SD-scores for SBMD (R = -0.48), TBBMD (R = -0.43), TBBMC (R
      = -0.46) (all p < 0.05) and positively with SDs-scores for FM (R = 0.44, p <
      0.05). CONCLUSION: Patients with FHA were characterized by lower concentrations
      of serum FSH, LH and estradiol concentrations. Moreover, FHA cases had decreased
      FM and an imbalanced relationship between BW, FM, and LBM. Despite reduced BMD
      and BMC, bone strength was not significantly affected by FHA.

PMID- 21957880
TI  - Associations between eNOS polymorphisms and susceptibility to Behcet's disease: a
      meta-analysis.
AB  - OBJECTIVE: To determine whether endothelial nitric oxide synthase (eNOS)
      polymorphisms confer susceptibility to Behcet's disease (BD). METHODS: A meta
      analysis was conducted on the associations between the G894T and 4b/a
      polymorphisms of eNOS and BD using: (i) the allele contrast, (ii) the recessive
      model, (iii) the dominant model and (iv) the additive model. RESULTS: A total of
      eight studies, which included 841 cases and 866 controls, were included in the
      meta-analysis. Meta-analysis of the G894T polymorphism revealed no association
      with BD in all study subjects or in Turkish and Asian populations. However, one
      Tunisian study of the T allele showed a significant association with BD (OR =
      0.707, 95% CI = 0.510-0.980, P = 0.038), but the OR of the T allele among
      Tunisians was lower, whereas it was higher in Europeans (OR = 2.129, 95% CI =
      1.407-3.220, P = 0.0003). Meta-analysis showed no association between BD and the
      4b/a polymorphism in all study subjects. Stratification by ethnicity indicated no
      significant association between the a allele of the 4b/a polymorphism and BD in
      Turkish and Asian populations. CONCLUSIONS: This meta-analysis shows that the
      eNOS G894T and the 4b/a polymorphisms are not associated with BD in the Turkish
      and Asian populations. These data suggest that the G894T and the 4b/a
      polymorphisms may not confer susceptibility to BD in the Turkish and Asian
      populations.

PMID- 21957882
TI  - How to explain the difficulties in the coffinite synthesis from the study of
      uranothorite?
AB  - The preparation of Th(1-x)U(x)SiO(4) uranothorite solid solutions was
      successfully undertaken under hydrothermal conditions (T = 250  degrees C). From
      XRD and EDS characterization, the formation of a complete solid solution between
      x = 0 (thorite) and x = 0.8 was evidenced. Nevertheless, additional (Th,U)O(2)
      dioxide and amorphous silica were systematically observed for the highest uranium
      mole loadings. The influence of kinetics parameters was then studied to avoid the
      formation of such side products. The variation of the synthesis duration allowed
      us to point out the initial formation of oxide phases then their evolution to a
      silicate phase through a dissolution/precipitation process close to that already
      described as coffinitization. Also, the uranium mole loading initially considered
      was found to significantly influence the kinetics of reaction, as this latter
      strongly slows down for x > 0.3. Under these conditions, the difficulties
      frequently reported in the literature for the synthesis of pure USiO(4) coffinite
      were assigned to a kinetic hindering associated with the coffinitization
      reaction.

PMID- 21957881
TI  - High-dose ursodeoxycholic acid increases risk of adverse outcomes in patients
      with early stage primary sclerosing cholangitis.
AB  - BACKGROUND: Ursodeoxycholic acid (UDCA) in a dose of 28-30 mg/kg/day increases
      the likelihood of clinical deterioration of primary sclerosing cholangitis (PSC)
      patients. AIM: To compare the risk of adverse clinical endpoints in patients with
      varying disease status. METHODS: We reviewed records from patients previously
      enrolled in a study evaluating the effects of high dose (28-30 mg/kg/day) UDCA in
      PSC. Patients were grouped according to treatment (UDCA vs. placebo) and baseline
      disease status (histological stage of PSC, total serum bilirubin). Development of
      clinical endpoints including death, liver transplantation, cirrhosis, oesophageal
      varices and cholangiocarcinoma was sought. RESULTS: A total of 150 patients were
      included of whom 49 patients developed endpoints. There was an increased
      development of endpoints among patients using UDCA vs. placebo (14 vs. 4,
      P=0.0151) with early histological disease (stage 1-2, n=88) but not with late
      stage (stage 3-4, n=62) disease (17 vs. 14, P=0.2031). Occurrence of clinical
      endpoints was also higher in patients receiving UDCA vs. placebo (16 vs. 2,
      P=0.0008) with normal bilirubin levels (total bilirubin <=1.0 mg/dL) but not in
      patients with elevated bilirubin levels (15 vs. 16, P=0.6018). Among patients not
      reaching endpoints 31.7% had normalisation of their alkaline phosphatase levels
      when compared to 14.3% in patients who reached endpoints (P=0.073). CONCLUSION:
      The increased risk of adverse events with UDCA treatment when compared with
      placebo is only apparent in patients with early histological stage disease or
      normal total bilirubin.

PMID- 21957883
TI  - Polymorphism in glutathione S-transferases: susceptibility and treatment outcome
      for head and neck cancer.
AB  - The study investigates the association of polymorphism in glutathione S
      transferases (GSTs) with susceptibility for head and neck squamous cell carcinoma
      (HNSCC) and its sites as well as treatment response in cases receiving
      chemotherapy (CT) and combination of CT-radiotherapy (CT-RT). The case-control
      study included 500 male cases and an equal number of healthy male controls. Odds
      ratios (ORs) and 95% confidence intervals (95% CI) were calculated for the
      association between genotypes and cancer risk. An increase in the risk for HNSCC
      and cancers of oral cavity, larynx or pharynx was observed in cases with null
      genotypes of GSTM1 or GSTT1. The interaction of alcohol or tobacco with variant
      genotypes of GSTM1 or GSTT1 also resulted in a significant increase in the risk
      for HNSCC. Further, HNSCC cases carrying the null genotypes of GSTM1 and GSTT1 or
      variant genotypes of GSTP1 showed a significant and superior treatment response.
      The present data thus provides evidence for the association of polymorphisms in
      GSTs with risk for HNSCC and its treatment response.

PMID- 21957884
TI  - Stereoselective metabolism of (+/-)-praeruptorin A, a calcium channel blocker
      from Peucedani Radix, in pooled liver microsomes of rats and humans.
AB  - (+/-)-Praeruptorin A (PA) is the major component of Peucedani Radix. The present
      study investigated stereoselectivity in PA metabolism in liver microsomes of rats
      (RLMs) and humans (HLMs), for the first time. PA was enantioseparated by semi
      preparative chiral HPLC. Metabolic profiles of the dextrorotatory (dPA) and the
      levorotatory (lPA) forms in HLMs and RLMs were determined using LC-MS/MS. (-)-cis
      Khellactone (D1) prepared from basic hydrolysis of dPA, and (3'R, 4'R)-4'
      angeloyl-khellactone (L8) and (3'R, 4'R)-3'-angeloyl-khellactone (L9) isolated
      from a scale-up incubation of lPA with rat plasma were unambiguously identified
      by LC-MS/MS and NMR analysis. Other metabolites were tentatively identified using
      LC-MS/MS. In the absence of NADPH-regenerating system, dPA remained intact,
      however, lPA yielded L8 and L9 via a carboxylesterase(s)-mediated process. In the
      presence of NADPH-regenerating system, lPA produced 9 (L1-9) metabolites in both
      species, while dPA generated 12 (D1-12) and 6 (D1-3, 6, 9 and 10) metabolites in
      RLMs and HLMs, respectively. Hydrolysis, oxidation and acyl migration were
      demonstrated to be the predominant pathways for both enantiomers. Both
      enantiomers were eliminated faster in RLMs than in HLMs, while lPA showed greater
      species difference. PA enantiomers exhibited stereoselective metabolism in RLMs
      and HLMs, implying chiral discrimination in their actions.

PMID- 21957885
TI  - Eyelid myokymia: not always benign.
AB  - A 33-year-old otherwise healthy male presented with a week-long history of
      isolated right lower eyelid myokymia. Two weeks later, the patient's myokymia had
      progressed to include twitching of the right brow and right upper lip. Imaging
      revealed multiple demyelinating lesions consistent with multiple sclerosis. A
      review of eyelid and facial myokymia, along with possible concerning causes is
      provided, geared towards the oculoplastic surgeon. Eyelid myokymia, typically a
      benign condition, may rarely evolve into facial myokymia reflective of underlying
      brainstem disease.

PMID- 21957886
TI  - Siloxyl ether functionalized resins for chemoselective enrichment of carboxylic
      acids.
AB  - Although the carboxylic acid moiety is prevalent in many biologically produced
      molecules, including natural products and proteins, methods to chemoselectively
      target this functional group have remained elusive. Generally, strategies that
      utilize carboxylate nucleophilicity also promote reactions with other
      nucleophiles such as amines and hydroxyls. A reagent was sought to facilitate the
      selective isolation of carboxylic acid containing compounds from complex
      mixtures. Here, the development of siloxyl ether functionalized solid supports is
      described.

PMID- 21957887
TI  - Factors predicting clinical outcome 12 and 36 months after an exercise
      intervention for recurrent low-back pain.
AB  - PURPOSE: The aim of this cohort study was to identify early predictive factors
      for a poor outcome of disability and pain 12- and 36-months after an intervention
      in patients with recurrent low-back pain, currently at work. METHOD: Seventy-one
      patients with recurrent low-back pain, all at work, seeking care in a primary
      health care setting were included. Predictive indicators including demographic
      data and health-related variables were derived from questionnaires pre- and post
      intervention over eight weeks. The dependent outcome variables were perceived
      disability and present pain at 12- and 36-months. RESULTS: Multivariate
      regression analyses show that early data on poor self-efficacy for physical
      activity, greater disability, and higher level of pain-ratings emerged as
      independent predictors of a poor outcome of disability at 12 and 36 months.
      Higher ratings of pain and poor self-efficacy appeared again as independent
      predictors of a poor outcome of pain at the 12-month follow-up. Pain frequency
      ratings predicted a poor outcome of pain at 36 months. CONCLUSIONS: Our results
      suggest that ratings of poor self-efficacy for physical activity, greater
      disability, and pain-ratings, are the most consistent independent predictors of
      long-term poor outcome of disability and pain. This indicates the importance of
      screening for such factors to optimize the management of low-back pain. However,
      larger studies in similar patient populations are needed to confirm these
      results.

PMID- 21957888
TI  - The 5-HT(1A) agonism potential of substituted piperazine-ethyl-amide derivatives
      is conserved in the hexyl homologues: molecular modeling and pharmacological
      evaluation.
AB  - In a series of carboxamide and sulphonamide alkyl (ethyl to hexyl) piperazine
      analogues, although the size of the linker is very different, ethyl and hexyl
      derivatives possess a high affinity for 5-HT(1A) receptors. Docking studies
      clearly show that hexyl and ethyl compounds favorably interact with the binding
      site of the active conformation of 5-HT(1A) receptors, thus confirming a possible
      agonist profile. This activity is effectively detected in electrophysiological
      experiments in which all four compounds inhibit the activity of rat dorsal raphe
      serotonergic neurons.

PMID- 21957889
TI  - Are you really angry? The effect of intensity on facial emotion recognition in
      frontotemporal dementia.
AB  - Frontotemporal dementia (FTD) is a neurodegenerative brain disorder that affects
      the frontal and temporal lobes predominantly. Impaired emotion recognition has
      been reported in two FTD subtypes: behavioral-variant FTD (bvFTD) and semantic
      dementia (SD), but has not been investigated in the third subtype: progressive
      nonfluent aphasia (PNFA). METHODS: Recognition of six basic facial emotions
      (anger, disgust, fear, sadness, surprise, and happiness) was investigated in 41
      FTD patients (bvFTD = 16; SD = 12; PNFA = 13) and 37 age- and education-matched
      controls, using two tests. In one task, intensity of emotional expression was
      increased to identify cognitive components contributing to emotion recognition
      performance. RESULTS: All patient groups demonstrated impaired overall facial
      emotion recognition compared to controls. Performance, however, improved with
      increased emotion intensity in bvFTD and PNFA groups, the effect of intensity on
      emotion recognition being particularly pronounced for negative emotions. In
      contrast, increased intensity of facial emotion did not change performance in SD.
      CONCLUSIONS: Patients with SD demonstrate a primary emotion processing
      impairment, whereas PNFA and bvFTD patients' emotional disturbance is in part
      mediated by attentional deficits. These findings indicate that a subset of FTD
      patients may benefit from enhanced emotional intensity that will facilitate
      facial emotion recognition.

PMID- 21957894
TI  - Gender, sexuality and the discursive representation of access and equity in
      health services literature: implications for LGBT communities.
AB  - BACKGROUND: This article considers how health services access and equity
      documents represent the problem of access to health services and what the effects
      of that representation might be for lesbian, gay, bisexual and transgender (LGBT)
      communities. We conducted a critical discourse analysis on selected access and
      equity documents using a gender-based diversity framework as determined by two
      objectives: 1) to identify dominant and counter discourses in health services
      access and equity literature; and 2) to develop understanding of how particular
      discourses impact the inclusion, or not, of LGBT communities in health services
      access and equity frameworks.The analysis was conducted in response to public
      health and clinical research that has documented barriers to health services
      access for LGBT communities including institutionalized heterosexism, biphobia,
      and transphobia, invisibility and lack of health provider knowledge and comfort.
      The analysis was also conducted as the first step of exploring LGBT access issues
      in home care services for LGBT populations in Ontario, Canada. METHODS: A
      critical discourse analysis of selected health services access and equity
      documents, using a gender-based diversity framework, was conducted to offer
      insight into dominant and counter discourses underlying health services access
      and equity initiatives. RESULTS: A continuum of five discourses that characterize
      the health services access and equity literature were identified including two
      dominant discourses: 1) multicultural discourse, and 2) diversity discourse; and
      three counter discourses: 3) social determinants of health (SDOH) discourse; 4)
      anti-oppression (AOP) discourse; and 5) citizen/social rights discourse.
      CONCLUSIONS: The analysis offers a continuum of dominant and counter discourses
      on health services access and equity as determined from a gender-based diversity
      perspective. The continuum of discourses offers a framework to identify and
      redress organizational assumptions about, and ideological commitments to, sexual
      and gender diversity and health services access and equity. Thus, the continuum
      of discourses may serve as an important element of a health care organization's
      access and equity framework for the evaluation of access to good quality care for
      diverse LGBT populations. More specfically, the analysis offers four important
      points of consideration in relation to the development of a health services
      access and equity framework.

PMID- 21957893
TI  - Metabolism of selenite in human lung cancer cells: X-ray absorption and
      fluorescence studies.
AB  - Selenite is an inorganic form of selenium that has a cytotoxic effect against
      several human cancer cell lines: one or more selenite metabolites are considered
      to be responsible for its toxicity. X-ray absorption spectroscopy was used to
      monitor Se speciation in A549 human lung cancer cells incubated with selenite
      over 72 h. As anticipated, selenodiglutathione and elemental Se both comprised a
      large proportion of Se in the cells between 4 and 72 h after treatment, which is
      in accordance with the reductive metabolism of selenite in the presence of
      glutathione and glutathione reductase/NADPH system. Selenocystine was also
      present in the cells but was only detected as a significant component between 24
      and 48 h concomitant with a decrease in the proportion of selenocysteine and the
      viability of the cells. The change in speciation from the selenol,
      selenocysteine, to the diselenide, selenocystine, is indicative of a change in
      the redox status of the cells to a more oxidizing environment, likely brought
      about by metabolites of selenite. X-ray fluorescence microscopy of single cells
      treated with selenite for 24 h revealed a punctate distribution of Se in the
      cytoplasm. The accumulation of Se was associated with a greater than 2-fold
      increase in Cu, which was colocalized with Se. Selenium K-edge extended X-ray
      absorption fine structure (EXAFS) spectroscopy revealed Se-Se and Se-S bonding,
      but not Se-Cu bonding, despite the spatial association of Se and Cu. Microprobe X
      ray absorption near-edge structure spectroscopy (MU-XANES) showed that the highly
      localized Se species was mostly elemental Se.

PMID- 21957892
TI  - Investigation of 95 variants identified in a genome-wide study for association
      with mortality after acute coronary syndrome.
AB  - BACKGROUND: Genome-wide association studies (GWAS) have identified new candidate
      genes for the occurrence of acute coronary syndrome (ACS), but possible effects
      of such genes on survival following ACS have yet to be investigated. METHODS: We
      examined 95 polymorphisms in 69 distinct gene regions identified in a GWAS for
      premature myocardial infarction for their association with post-ACS mortality
      among 811 whites recruited from university-affiliated hospitals in Kansas City,
      Missouri. We then sought replication of a positive genetic association in a
      large, racially diverse cohort of myocardial infarction patients (N = 2284) using
      Kaplan-Meier survival analyses and Cox regression to adjust for relevant
      covariates. Finally, we investigated the apparent association further in 6086
      additional coronary artery disease patients. RESULTS: After Cox adjustment for
      other ACS risk factors, of 95 SNPs tested in 811 whites only the association with
      the rs6922269 in MTHFD1L was statistically significant, with a 2.6-fold mortality
      hazard (P = 0.007). The recessive A/A genotype was of borderline significance in
      an age- and race-adjusted analysis of the entire combined cohort (N = 3095; P =
      0.052), but this finding was not confirmed in independent cohorts (N = 6086).
      CONCLUSIONS: We found no support for the hypothesis that the GWAS-identified
      variants in this study substantially alter the probability of post-ACS survival.
      Large-scale, collaborative, genome-wide studies may be required in order to
      detect genetic variants that are robustly associated with survival in patients
      with coronary artery disease.

PMID- 21957895
TI  - Nanoscale chemical imaging of single-layer graphene.
AB  - Electronic properties in different graphene materials are influenced by the
      presence of defects and their relative position with respect to the edges. Their
      localization is crucial for the reliable development of graphene-based electronic
      devices. Graphene samples produced by standard CVD on copper and by the scotch
      tape method on gold were investigated using tip-enhanced Raman spectroscopy
      (TERS). A resolution of <12 nm is reached using TERS imaging with full spectral
      information in every pixel. TERS is shown to be capable of identifying defects,
      contaminants, and pristine graphene due to their different spectroscopic
      signatures, and of performing chemical imaging. TERS allows the detection of
      smaller defects than visible by confocal Raman microscopy and a far more precise
      localization. Consecutive scans on the same sample area show the reproducibility
      of the measurements, as well as the ability to zoom in from an overview scan onto
      specific sample features. TERS images can be acquired in as few as 5 min with 32
      * 32 pixels. Compared to confocal Raman microscopy, a high sensitivity for
      defects, edges, hydrogen-terminated areas or contaminated areas (in general for
      deviations from the two-dimensional structure of pristine graphene) is obtained
      due to selective enhancement as a consequence of the orientation in the
      electromagnetic field.

PMID- 21957896
TI  - The effect of quinapril treatment on insulin resistance, leptin and high
      sensitive C-reactive protein in hypertensive patients.
AB  - The aim of the study was to evaluate the effect of quinapril on HOMA-IR, high
      sensitive C-reactive protein and leptin. Total 54 hypertensive and 24 control
      subjects were included in this study. Blood pressure, leptin, high sensitive C
      reactive protein, and HOMA-IR were determined at baseline and after 3 months
      quinapril treatment. After treatment with quinapril HOMA-IR (p = 0.04), high
      sensitive C-reactive protein (p = 0.027), and leptin (p = 0.046) were decreased
      in hypertensive patients. Quinapril may be used as a therapy for improving blood
      pressure as well as the insulin resistant, hyperleptinemic, and low-grade
      inflammatory state in hypertension.

PMID- 21957897
TI  - Meta-analysis of the studies of bleeding complications of platelets pathogen
      reduced with the Intercept system.
AB  - BACKGROUND: The eligibility criteria of a previously reported meta-analysis
      (Transfusion 2011;51:1058-1071) of randomized controlled trials (RCTs) of
      pathogen reduction of platelets in patients with hypoproliferative
      thrombocytopenia were modified to examine the impact on the findings of: (1)
      inclusion of a (previously excluded) RCT; (2) restriction of eligibility to RCTs
      of the Intercept (amotosalen-HCl/ultraviolet-A-light) system; and (3) differences
      in the methods used to assess bleeding complications. MATERIALS AND METHODS: Five
      RCTs comparing the risk of all, clinically significant (grades 2 through 4)
      and/or severe (grades 3 and 4) bleeding complications between recipients of
      platelets treated with Intercept vs. standard unmanipulated platelets were
      included. Odds ratios (ORs) of bleeding complications of similar severity
      recorded during similar periods of observation were calculated across all studies
      and across homogeneous subsets of studies by random-effects methods. RESULTS:
      Treatment with Intercept increased all bleeding complications when four RCTs
      meeting the eligibility criteria of the previous meta-analysis were integrated,
      but not across all the five currently available studies [summary OR=1.24; 95%
      confidence interval (CI), 0.79-1.93]. Clinically significant bleeding
      complications increased when the results of the SPRINT RCT were based on the
      expanded safety analysis (summary OR=1.52; 95% CI, 1.09-2.12)--but not the
      initial report (summary OR=1.30; 95% CI, 0.54-3.14)--of that study. CONCLUSIONS:
      Treatment with Intercept may increase the risk of all and clinically significant
      (albeit not severe) bleeding complications in RCTs maintaining a platelet count
      of >=10*10(9) or >=20*10(9)/l through increased platelet transfusions.

PMID- 21957898
TI  - Variation of straylight between contra lateral eyes - results from 1017 healthy
      subjects.

PMID- 21957899
TI  - Leptin and cardiovascular diseases.
AB  - 1. Leptin is a 16-kDa hormone, synthesized primarily by adipocyte, which acts as
      a key factor for maintenance of energy homeostasis in central and peripheral
      tissues. In most obese individuals, serum leptin levels are increased and
      correlate with the individual's body mass index. 2. Abundant investigations
      ranging from clinical and animal model studies to in vitro analyses show that
      leptin plays a pivotal role in obesity-related cardiovascular diseases (CVD).
      Hyperleptinaemia has been confirmed to be a predictor of acute cardiovascular
      events. However, some studies have shown that leptin has a cardioprotective
      effect in leptin-deficient models. These data suggest the influences of leptin on
      the pathophysiology of cardiovascular diseases are complex and not completely
      understood. 3. In the present review, we summarize the major leptin signalling
      pathways, including Janus-activated kinase/signal transducers and activators of
      transcription (Jak/STAT), mitogen-activated protein kinases (MAPK), and
      phosphatidylinositol 3-kinase (PI-3K) signalling pathways, and analyse the
      probable mechanisms of selective leptin resistance. We then provide a detailed
      review of the effects of leptin on the cardiovascular system, including
      sympathoactivation, oxidative stress, vascular inflammation, endothelial
      dysfunction, vascular cell proliferation, cardiomyocytes hypertrophy, as well as
      fatty acid metabolism, all of which contribute to the pathogenesis of
      cardiovascular diseases (e.g. ischaemic heart disease). The central premise of
      this review is to elucidate the mechanisms by which leptin affects the
      cardiovascular function and provide insight into obesity-related CVD.

PMID- 21957900
TI  - Asymmetric large for gestational age newborns in pregnancies complicated by
      diabetes mellitus: is maternal obesity a culprit?
AB  - OBJECTIVE: Evaluate the association between body mass index (BMI) and the
      delivery of an asymmetrically large for gestational age (A-LGA) newborn in women
      with diabetes. METHODS: Retrospective analysis of 306 pregnancies complicated by
      Type 1 and 55 by Type 2 diabetes. RESULTS: The prevalence of Type 1 and Type 2
      diabetics delivering large for gestational age (LGA) infants was 42% and 49%,
      respectively. Of these 49% and 55% were A-LGA, respectively. Pre-pregnancy BMI
      was not associated with increased odds of delivering an A-LGA newborn in women
      with Type 1 or 2 diabetes. However, in Type 1 diabetics, each one-pound increase
      in maternal weight during pregnancy resulted in 4% increased odds of delivering
      an A-LGA newborn. For Type 2 diabetics, the odds of delivering an A-LGA infant
      was decreased by 10% for each 0.1 unit/kg increase in insulin dose. CONCLUSION:
      Although there is a known association between obesity and LGA in women with
      diabetes, we found that overweight and obese women with Type 1 or Type 2 diabetes
      do not have increased odds of delivering an A-LGA newborn. However, insulin dose
      in Type 2 diabetes and maternal weight gain in Type 1 diabetes were significantly
      associated with the odds of delivering an A-LGA neonate.

PMID- 21957901
TI  - Pulsed dye laser as an excellent choice of treatment for lupus tumidus: a
      prospective study.
AB  - BACKGROUND: Clinical manifestations of cutaneous lupus erythematosus (CLE) vary
      widely, and different subtypes of this autoimmune disease exist. Tumidus subtype
      (LT) has been recently separated from the chronic subtypes and is now considered
      an independent entity due to its particular clinical and histological features.
      Different treatments are usually prescribed for CLE. Our group has experience of
      CLE effectively treated with pulsed dye laser (PDL). It was our impression that
      better responses were achieved in the LT subtype, but no controlled prospective
      studies with PDL have been specifically performed. MATERIALS AND METHODS: A
      prospective study was performed on 10 patients with histologically confirmed LT
      treated with PDL. All patients were treated with 595 nm PDL using the 10 mm spot
      size at 0.5 ms pulse width and a fluence of 8 J/cm(2). Biopsies were taken before
      and 4 weeks after treatment and were stained with haematoxylin-eosin. RESULTS:
      Evaluation after PDL treatment showed clinical improvement in all of them without
      side-effects and reduction of the dermal lymphocytic infiltrate in 9/10 of the
      patients. Epidermal changes were absent in all patients. Mucin deposition
      persisted only in one patient. However, 50% of the patients developed new lesions
      nearby or distant to the treated zones. CONCLUSIONS: PDL therapy is an effective
      and fast treatment option for acute flares of LT; however, it does not prevent
      recurrences. A histological improvement has been confirmed in this study. Purpura
      seems to be necessary to achieve a good response.

PMID- 21957902
TI  - AMP-activated protein kinase downregulates Kv7.1 cell surface expression.
AB  - The potassium channel Kv7.1 is expressed in the heart, where it contributes to
      the repolarization of the cardiac action potential. Additionally, Kv7.1 is
      expressed in epithelial tissues playing a role in salt and water transport. We
      recently demonstrated that surface-expressed Kv7.1 is internalized in response to
      polarization of the epithelial Madin-Darby canine kidney (MDCK) cell line and
      that this was mediated by activation of protein kinase C (PKC). In this study,
      the pathway downstream of PKC, which leads to internalization of Kv7.1 upon cell
      polarization, is elucidated. We show by confocal microscopy that Kv7.1 is
      endocytosed upon initiation of the polarization process and sent for degradation
      by the lysosomal pathway. The internalization could be mimicked by
      pharmacological activation of the AMP-activated protein kinase (AMPK) using three
      different AMPK activators. We demonstrate that the downstream effector of AMPK is
      the E3 ubiquitin ligase Nedd4-2. Additionally, we show that AMPK activation
      results in a downregulation of Kv7.1 currents in Xenopus oocytes through a Nedd4
      2-dependent mechanism. In summary, surface-expressed Kv7.1 channels are
      endocytosed and sent for degradation in lysosomes by an AMPK-mediated activation
      of Nedd4-2 during the initial phase of the MDCK cell polarization process.

PMID- 21957903
TI  - Propofol infusion syndrome with severe and dynamic Brugada electrocardiogram but
      benign clinical outcome.

PMID- 21957905
TI  - Gd(III) chelates as NMR probes of protein-protein interactions. Case study:
      rubredoxin and cytochrome c3.
AB  - Two cyclen-derived Gd probes, [Gd-DOTAM](3+) and [Gd-DOTP](5-) (DOTAM = 1,4,7,10
      tetraazacyclododecane-1,4,7,10-tetraacetamide; DOTP = 1,4,7,10
      tetraazacyclododecane-1,4,7,10-tetrakis(methylenephosphonate)), were assessed as
      paramagnetic relaxation enhancement (PRE)-inducing probes for characterization of
      protein-protein interactions. Two proteins, Desulfovibrio gigas rubredoxin and
      Desulfovibrio gigas cytochrome c(3), were used as model partners. In a (1)H NMR
      titration it was shown that [Gd-DOTP](5-) binds to cytochrome c(3) near heme IV,
      causing pronounced PREs, characterized by line width broadenings of the heme
      methyl resonances at ratios as low as 0.08. A K(d) of 23 +/- 1 MUM was calculated
      based on chemical shift perturbation of selected heme methyl resonances belonging
      to three different heme groups, caused by allosteric effects upon [Gd-DOTP](5-)
      binding to cytochrome c(3) at a molar ratio of 2. The other probe, [Gd
      DOTAM](3+), caused PREs on a well-defined patch near the metal center of
      rubredoxin (especially the patch constituted by residues D19-G23 and W37-S45,
      which broaden beyond detection). This effect was partially reversed for some
      resonances (C6-Y11, in particular) when cytochrome c(3) was added to this system.
      Both probes were successful in causing reversible PREs at the partner binding
      site, thus showing to be good probes to identify partners' binding sites and
      since the interaction is reversible to structurally characterize protein
      complexes by better defining the complex interface.

PMID- 21957906
TI  - Psoriasis associated with anti-tumour necrosis factor therapy in inflammatory
      bowel disease: a new series and a review of 120 cases from the literature.
AB  - BACKGROUND  Anti-tumour necrosis factor (TNF) antibodies are used to treat both
      psoriasis and inflammatory bowel disease. The seemingly paradoxical occurrence of
      psoriasis in patients treated with anti-TNF antibodies is increasingly
      recognised, but the distinct features associated with inflammatory bowel disease
      have been incompletely characterised. AIM  To identify inflammatory bowel disease
      patients who developed psoriasis while receiving an anti-TNF antibody at two
      academic medical centres between 2000 and 2009 and review all published cases of
      this phenomenon in inflammatory bowel disease. METHODS  We identified
      retrospectively all cases of anti-TNF-induced psoriasis in inflammatory bowel
      disease patients attending two North American healthcare centres. We analysed
      these cases alongside the published reports of anti-TNF-induced psoriasis.
      RESULTS  We identified 30 subjects who developed a psoriatic rash while receiving
      anti-TNF therapy for inflammatory bowel disease. Forty-seven per cent (14/30)
      responded to topical therapy and 23% (7/30) ultimately discontinued the anti-TNF.
      The new data were combined with those from 120 published cases of anti-TNF
      induced psoriasis in inflammatory bowel disease. Anti-TNF-induced psoriasis in
      inflammatory bowel disease was more common in women (70%). The most common
      distributions were palmoplantar (43%) and scalp (42%). Complete follow-up in 148
      cases showed that 41% responded to topical therapy but 43% required definitive
      withdrawal of anti-TNF therapy due to the rash. A second anti-TNF was tried in 27
      cases with recurrence or persistence of the rash in 14 (52%). CONCLUSIONS  In
      this analysis, psoriasiform lesions related to anti-TNF therapy in inflammatory
      bowel disease occurred most commonly in women. Approximately 41% of those who
      developed psoriasis while on anti-TNFs responded to topical therapy and were able
      to continue the drug, while 52% of those treated with an alternate anti-TNF had
      recurrence of the rash.

PMID- 21957907
TI  - Undifferentiated carcinoma of the lacrimal sac: case report and review of
      literature.
AB  - A 55-year-old man presented with a 2-year history of right-sided epiphora and was
      referred to the Oculoplastic services for dacryocystorhinostomy. A 3-month
      progressive growth of a right medial canthal mass was found. MRI revealed an
      extraconal, lobulated, homogeneously enhancing mass in the lacrimal sac fossa
      with globe indentation and displacement supero-temporally. Following a
      transcanalicular needle biopsy which was suggestive of a carcinoma, he underwent
      medial orbitectomy and maxillectomy, through a lateral rhinotomy, with removal of
      puncta and canaliculi after ensuring no regional or systemic spread. The lacrimal
      sac tumor was encapsulated, extending superiorly above the medial canthal tendon
      and involving the nasolacrimal duct, and posteriorly along the medial orbital
      wall. After ensuring surgical margins were cleared of tumor infiltration, orbital
      reconstruction was performed with titanium plate and nasolabial flap. He has
      completed adjuvant radiotherapy with no evidence of tumor recurrence at 15 months
      of follow-up.

PMID- 21957908
TI  - International Organization of Physical Therapy in Mental Health consensus on
      physical activity within multidisciplinary rehabilitation programmes for
      minimising cardio-metabolic risk in patients with schizophrenia.
AB  - PURPOSE: The excess cardiovascular morbidity associated with schizophrenia is
      attributed to an interplay between behavioural (physical inactivity, unhealthy
      diet, substance abuse), genetic and illness related factors, as well as the
      effects of antipsychotic treatment. Patients have limited access to physical
      healthcare with less opportunity for cardiovascular risk prevention and treatment
      programmes than the non-psychiatric population. The aim of this paper is to
      improve physical activity (PA) within rehabilitation programmes for people with
      schizophrenia. METHOD: The development process consisted of: a) systematic
      literature review on PA in schizophrenia in eight databases up to May 2010; b)
      review on existing national and international guidelines; c) consensus meetings,
      and d) formulation of the final consensus document. RESULTS: There is
      insufficient evidence for the relative contribution of PA reducing cardio
      metabolic risks in people with schizophrenia. Demographical, biological,
      psychological, cognitive-behavioural, emotional, social and environmental
      barriers for PA could be identified. CONCLUSIONS: Although PA outcomes on cardio
      metabolic parameters are still unknown, the benefits of physical activity as part
      of a larger lifestyle programme are sufficient for the recommendation that
      persons with schizophrenia follow the 2008 U.S. Department of Health and Human
      Services PA Guidelines with specific adaptations based on disease and treatment
      related adverse effects.

PMID- 21957909
TI  - Structure of the mRNA splicing complex component Cwc2: insights into RNA
      recognition.
AB  - The Prp19-associated complex [NTC (nineteen complex)] plays a crucial role in
      intron removal during premature mRNA splicing in eukaryotes. Only one component
      of the NTC, Cwc2, is capable of binding RNA. In the present study we report the
      1.9 A (1 A=0.1 nm) X-ray structure of the Cwc2 core domain, which is both
      necessary and sufficient for RNA binding. The Cwc2 core domain contains two sub
      domains, a CCCH-type ZnF (zinc finger) and a RRM (RNA recognition motif).
      Unexpectedly, the ZnF domain and the RRM form a single folding unit, glued
      together by extensive hydrophobic interactions and hydrogen bonds. Structure
      guided mutational analysis revealed that the intervening loop [known as the RB
      loop (RNA-binding loop)] between ZnF and RRM plays an essential role in RNA
      binding. In addition, a number of highly conserved positively charged residues on
      the beta-strands of RRM make an important contribution to RNA binding.
      Intriguingly, these residues and a portion of the RB loop constitute an extended
      basic surface strip that encircles Cwc2 halfway. The present study serves as a
      framework for understanding the regulatory function of the NTC in RNA splicing.

PMID- 21957915
TI  - Abstracts of the 22nd Australasian Society of Clinical Immunology and Allergy
      (ASCIA) Annual Scientific Meeting. Darling Harbour, Sydney, NSW, Australia.
      September 7-9, 2011.

PMID- 21957910
TI  - Organ specific regenerative markers in peri-organ adipose: kidney.
AB  - BACKGROUND: Therapeutically bioactive cell populations are currently understood
      to promote regenerative outcomes in vivo by leveraging mechanisms of action
      including secretion of growth factors, site specific engraftment and directed
      differentiation. Constitutive cellular populations undoubtedly participate in the
      regenerative process. Adipose tissue represents a source of therapeutically
      bioactive cell populations. The potential of these cells to participate in
      various aspects of the regenerative process has been demonstrated broadly.
      However, organ association of secretory and developmental markers to specific
      peri-organ adipose depots has not been investigated. To characterize this
      topographical association, we explored the potential of cells isolated from the
      stromal vascular fraction (SVF) of kidney sourced adipose to express key renal
      associated factors. RESULTS: We report that renal adipose tissue is a novel
      reservoir for EPO expressing cells. Kidney sourced adipose stromal cells
      demonstrate hypoxia regulated expression of EPO and VEGF transcripts. Using iso
      electric focusing, we demonstrate that kidney and non-kidney sourced adipose
      stromal cells present unique patterns of EPO post-translational modification,
      consistent with the idea that renal and non-renal sources are functionally
      distinct adipose depots. In addition, kidney sourced adipose stromal cells
      specifically express the key renal developmental transcription factor WT1.
      CONCLUSIONS: Taken together, these data are consistent with the notion that
      kidney sourced adipose stromal (KiSAS) cells may be primed to recreate a
      regenerative micro-environment within the kidney. These findings open the
      possibility of isolating solid-organ associated adipose derived cell populations
      for therapeutic applications in organ-specific regenerative medicine products.

PMID- 21957916
TI  - A review of factors that influence adult handwriting performance.
AB  - BACKGROUND: Handwriting is an important activity for people of all ages.
      Handwriting is frequently affected after stroke and other neurological
      conditions. However, research on the handwriting of healthy adults is difficult
      to find. This review aims to advance the development of evidence-informed
      handwriting assessment and retraining. AIM: The aim of this paper was to review
      factors that influence the handwriting performance of unimpaired adults, some of
      which are amenable to intervention. METHODS: Searches were conducted of eight
      electronic databases up to April 2009 and again in November 2010. Reference lists
      were also used to identify potential studies of interest. No limits were placed
      on study design. FINDINGS:  Age: Younger adults write more legibly and faster
      than older adults. Gender: Women write faster and more legibly than men. Pengrip:
      Grips other than the traditional dynamic tripod are functional, producing legible
      text in an acceptable time. Pen pressure: Pressure varies with different letters,
      words, text size, speed and across a page of text. Error corrections and a mixed
      writing style occur in healthy adult handwriting. Research was inconclusive about
      the association between speed, pressure and upper limb movements on handwriting
      performance. Other factors able to predict adult handwriting legibility have been
      largely unexplored. DISCUSSION: A number of knowledge and research gaps about
      adult handwriting were identified, including the need for more contemporary
      normative data.

PMID- 21957917
TI  - Is occupation missing from occupational therapy in palliative care?
AB  - BACKGROUND/AIM: The role of occupational therapists in palliative care is largely
      undocumented in Western Australia (WA). Little is known about the services
      occupational therapists provide or the needs of people who are dying and their
      carers in relation to these services. The aims of this study were as follows.
      First, to determine the number of occupational therapists employed and the range
      of services they provide in palliative care in WA. Second, with particular
      reference to self care, leisure, productive roles and occupations, to explore the
      daily experiences of people who were dying as well as their primary carers to
      determine the services that might be offered by occupational therapy to this
      population. METHODS: Semi-structured interviews were used to gather information
      from carers (n=10 metro, n=4 rural) and occupational therapists (n = 13 metro, n
      = 5 rural). Data were analysed qualitatively using grounded theory to develop
      categories. Themes were defined using the constant comparison method. RESULTS:
      Four themes emerged that impacted people who were dying and their carers. These
      were; ongoing disengagement from usual activities with resultant occupational
      deprivation; disempowerment of both people who are dying and their carers within
      palliative care services; 'occupation' not being addressed adequately in
      palliative care, and occupational therapists experience frustration with limited
      opportunities to contribute to the care of people who are dying. CONCLUSIONS:
      This paper highlights gaps in service provision in WA to people who are dying and
      their carers. It provides direction for occupational therapists to offer an
      occupation-focussed approach to the care of this vulnerable group.

PMID- 21957918
TI  - Evaluating an online occupational therapy community of practice and its role in
      supporting occupational therapy practice.
AB  - BACKGROUND/AIM:   Networking, together with knowledge acquisition and resource
      sharing, are key components of occupational therapists' professional development.
      To enhance the connectedness and clinical support available to occupational
      therapists, OT AUSTRALIA Queensland developed an online community of practice
      (CoP). No research regarding the use of online CoPs by occupational therapists
      has been conducted. This study aimed to explore occupational therapists'
      perceptions of the benefits of, barriers to, and reasons for using or not using
      the online CoP. METHODS:   Two focus groups were conducted, one with therapists
      who had used the CoP (n = 5) and the other with therapists who had not used it (n
      = 9). Participant responses to focus group questions informed the development of
      a survey asking therapists about their use of the CoP, its benefits and reasons
      for using/not using it, which was sent via email to all OT AUSTRALIA Queensland
      members. RESULTS: Motivation to use the CoP, technology, workload management
      impacts, potential benefits and time considerations emerged as themes from the
      focus groups. Of the 55 survey respondents, 58.2% were aware of the CoP but only
      32.7% had accessed it. Potential benefits of the CoP identified by participants
      included time efficiency, structural flexibility, networking capabilities and
      mentoring opportunities. Reasons for not accessing and/or participating in the
      CoP included access difficulties, usability difficulties, personal communication
      preferences and perceived irrelevance of available information. CONCLUSION: The
      findings of this study suggest that the CoP is still in the early stages of
      development; however, it has the potential to be further embraced by therapists
      if further promotion, training and minor usability modifications are undertaken.

PMID- 21957919
TI  - Pressure care practice and occupational therapy: findings of an exploratory
      study.
AB  - BACKGROUND/AIM: Pressure ulcers are a severe and costly yet usually preventable
      burden on health-care systems worldwide. Occupational therapists are recognised
      members of the multidisciplinary team involved in the provision of pressure care.
      However, published evidence supporting their role is limited. The aim of this
      study was to explore the profile of occupational therapy in pressure care to gain
      an Australian perspective on current practice. METHODS: A cross-sectional self
      administered online survey was developed and distributed through OT AUSTRALIA to
      collect responses from practicing occupational therapists across Australia.
      RESULTS: A total of 277 completed surveys were returned. Aged care formed the
      largest practice area group with 38% of the sample. Over half of the participants
      worked in community settings (53%) and were involved in pressure care on a
      regular basis. Risk assessment scales were used by 84% of participants with the
      Waterlow being the most frequently administered scale (61%). The most frequently
      used interventions were the prescription of seating surfaces and pressure relief
      mattresses, education of the client (weight shifting and skin care), transfer
      training and increasing physical activity to relieve pressure, all identified by
      over 80% of the sample. CONCLUSIONS: Occupational therapists play a critical role
      in the prevention and treatment of pressure ulcers and are expected to make best
      practice, cost-effective decisions with a limited evidence base to support them.
      Results of this study highlight the need for pressure care practice to be
      explored further, particularly in community aged care settings.

PMID- 21957920
TI  - Australian norms for handwriting speed in healthy adults aged 60-99 years.
AB  - AIM: Normative adult handwriting speed data were last collected in Australia in
      1982 using the Jebsen writing speed test. Updated norms are required by
      clinicians who measure and retrain handwriting. This study aimed to obtain and
      describe the range of normative scores for handwriting speed in healthy adults
      aged 60-99 years. METHODS: A descriptive cohort design was used. Tests included
      the Handwriting Speed Test (HST), Jebsen speed test, a self-generated sentence
      and shopping list, completed in pencil and pen. A sample of 120 healthy older
      Australians across four age cohorts was recruited (60-69; 70-79; 80-89; and 90-99
      years). RESULTS: HST: Mean letters/minute (SD) ranged from 113.3 (21.12) for
      younger men (60-69 years), to 66.8 (18.73) for older men (90-99 years), and 113.4
      (17.57) for younger women to 61.0 (17.57) for older women. Jebsen speed test:
      Mean speed (seconds to copy a 24-letter sentence) ranged from 11.97 (2.62)
      seconds for younger men to 22.35 (7.73) seconds for older men, and 12.05 (2.41)
      seconds for younger women to 23.60 (8.80) for older women. Copied text was
      written faster than self-generated text, and faster in pen than pencil. No
      significant differences were found in handwriting speed between men and women.
      Overall, speed decreased with increasing age. CONCLUSIONS: This sample wrote the
      Jebsen test sentence more quickly than age-matched peers in earlier studies,
      suggesting that norms should be updated regularly. Findings will inform
      therapists about factors affecting adult handwriting speed.

PMID- 21957921
TI  - Task-specific practice of dressing tasks in a hospital setting improved dressing
      performance post-stroke: a feasibility study.
AB  - BACKGROUND: Practise of personal activities of daily living, including dressing
      improves outcomes for people living at home after a stroke. Less is known about
      dressing outcomes for hospital inpatients. AIM: This study aimed to investigate
      the feasibility and outcomes of a group-based, task-specific dressing retraining
      programme for inpatients post-stroke. METHODS: A pre-post single group study
      design was used. Retrospective data were collected for stroke inpatients admitted
      to one hospital between 2007 and 2009. Participants attended a one-hour dressing
      group twice weekly during admission, supervised by occupational therapists. Each
      participant had one or more dressing goals. Scores on the Functional Independence
      Measure (FIM) upper and lower body dressing items were compared at baseline and
      at discharge. RESULTS: Of 119 participants who received group-based training, a
      mean improvement was found of 2.2 FIM points (95% CI 1.9-2.5, P = 0.0001) for
      upper body dressing (range 0-7), 2.7 FIM points (95% CI 2.3-3.1, P = 0.0001) for
      lower body dressing (range 0-7) and 5.2 FIM points (95% CI 4.5-6.0, P = 0.0001)
      for total dressing scores (range 0-14). Of 242 goals recorded, 48% focussed on
      shirt/upper body dressing, 35% on pants/shorts, 11% on socks and shoes and 13%
      involved buttons/fastenings. CONCLUSIONS: Task-specific practice of dressing
      tasks in a group setting was feasible and made clinically significant differences
      to dressing performance during inpatient rehabilitation. More rigorous methods of
      investigation are required in future to minimise selection, measurement and
      intervention biases.

PMID- 21957922
TI  - International fieldwork placements and occupational therapy: lived experiences of
      the major stakeholders.
AB  - INTRODUCTION: Occupational therapy students obtain a great deal of their
      professional preparation and experience through fieldwork placements. Although
      many occupational therapy students have taken part in international fieldwork
      placements, there is little research on this topic. As fieldwork placements are
      an integral part of the education of occupational therapy students, literature on
      the subject of international fieldwork placements is necessary. Accordingly, the
      aim of this study was to examine the personal and professional experiences of
      occupational therapy students, supervisors, and on-site staff who have taken part
      in an international fieldwork placement. METHODS: Qualitative interviews for this
      phenomenological study were administered with 14 participants who had taken part
      in an international fieldwork placement in Trinidad and Tobago. Data were
      analysed using thematic analysis. FINDINGS: Three themes emerged: collaborative
      learning, cultural negotiations and thinking on my own. DISCUSSION: Considering
      fieldwork is a critical component in the occupational therapy curriculum, it is
      reassuring to uncover that international placements can be of benefit to all
      stakeholders while achieving its primary goal of preparing students to become
      competent therapists. All participants developed a greater cultural awareness and
      appreciation, which is necessary as occupational therapists are increasingly
      working in diverse settings with diverse client groups. This information can also
      be used to enhance international fieldwork education as students continue to
      travel abroad to complete their mandatory fieldwork hours.

PMID- 21957923
TI  - Utopian visions/dystopian realities: exploring practice and taking action to
      enable human rights and occupational justice in a hospital context.
AB  - AIM: This article reports some preliminary findings of an Australian action
      research project that aimed to investigate, and affect, occupational therapists'
      understanding of human rights theory and occupational justice philosophy in
      everyday occupational therapy practice. METHOD: Over the course of one year, nine
      therapists from a range of practice areas in a major metropolitan hospital
      participated in monthly discussion groups. Narrative data was collected through
      audio-recording and transcribing the discussions. Data was qualitatively analysed
      using line-by-line coding and theme-building. RESULTS: Two preliminary themes are
      discussed herein: the invisibility of human rights issues in an Australian
      occupational therapy setting and the dissonance between the ideal and the reality
      of human rights practice in occupational therapy. CONCLUSION: The authors suggest
      that through discussion, and with the support of a community of practice
      dedicated to exploring human rights and occupational justice issues, occupational
      therapists can increase their awareness of human rights challenges. And,
      therapists can increase their actions to better enable occupational justice in
      their practice.

PMID- 21957924
TI  - Optimising motor adaptation in childhood obesity.

PMID- 21957925
TI  - Commentary on 'Helping children with autism spectrum disorders and their
      families: are we losing our occupation-centred focus?'.

PMID- 21957927
TI  - Assessment of patients' decision-making capacity: a response to a paper by
      Professor Darzins.

PMID- 21957929
TI  - Fine tuning the energetics of excited-state intramolecular proton transfer
      (ESIPT): white light generation in a single ESIPT system.
AB  - Using 7-hydroxy-1-indanone as a prototype (I), which exhibits excited-state
      intramolecular proton transfer (ESIPT), chemical modification has been performed
      at C(2)-C(3) positions by fusing benzene (molecule II) and naphthalene rings,
      (molecule III). I undergoes an ultrafast rate of ESIPT, resulting in a unique
      tautomer emission (lambda(max) ~530 nm), whereas excited-state equilibrium is
      established for both II and III, as supported by the dual emission and the
      associated relaxation dynamics. The forward ESIPT (normal to proton-transfer
      tautomer species) rates for II and III are deduced to be (30 ps)(-1) and (22 ps)(
      1), respectively, while the backward ESIPT rates are (11 ps)(-1) and (48 ps)(-1).
      The ESIPT equilibrium constants are thus calculated to be 0.37 and 2.2 for II and
      III, respectively, giving a corresponding free energy change of 0.59 and -0.47
      kcal/mol between normal and tautomer species. For III, normal and tautomer
      emissions in solid are maximized at 435 and 580 nm, respectively, achieving a
      white light generation with Commission Internationale de l'Eclairage (CIE) (0.30,
      0.27). An organic light-emitting diode based on III is also successfully
      fabricated with maximum brightness of 665 cd m(-2) at 20 V (885 mA cm(-2)) and
      the CIE coordinates of (0.26, 0.35). The results provide the proof of concept
      that the white light generation can be achieved in a single ESIPT system.

PMID- 21957930
TI  - Expanding the repertoire of natural product-inspired ring pairs for molecular
      recognition of DNA.
AB  - A furan amino acid, inspired by the recently discovered proximicin natural
      products, was incorporated into the scaffold of a DNA-binding hairpin polyamide.
      While unpaired oligomers of 2,4-disubstituted furan amino acids show poor DNA
      binding activity, furan (Fn) carboxamides paired with N-methylpyrrole (Py) and N
      methylimidazole (Im) rings demonstrate excellent stabilization of duplex DNA as
      well as discrimination of noncognate sequences, consistent with function as a Py
      mimic according to the Py/Im polyamide pairing rules.

PMID- 21957931
TI  - Clinical characteristics of young-onset and medical treatment-requiring
      hypertension identified by targeted screening in university health check-up.
AB  - Based on targeted screening for hypertension at a university health check-up, we
      previously reported a high incidence of white-coat hypertension and estimated
      prevalence of hypertension requiring medical treatments (HT) as around 0.1% in
      young population aged less than 30. In spite of such low prevalence, continuous
      screening for seven consecutive years (2003-2009) increased the number of HT
      students to 20 (19 males and 1 female). We presently assessed the clinical
      characteristics of these HTs. Renovascular hypertension was found in the only
      female HT and aortic valve regurgitation in two HTs. Resting 17 HTs were
      diagnosed as having essential hypertension (EH). A father and/or a mother had EH
      in 16 out of 17 EHs, and blood pressure (BP) at home was slightly elevated (135
      145 mm Hg in systolic) except three obese EHs (body mass index more than 30) who
      demonstrated more than 160 mm Hg in systolic. Plasma aldosterone-renin ratio
      (ARR) of EHs did not differ from that of normal controls, and Pearson correlation
      coefficient (R) between ARR and systolic BP (SBP) was -0.2. Its partial
      correlation coefficient, however, was statistically significant (R = -0.55, P =
      .026) after correcting for body mass index, which was significantly correlated
      with both SBP (P = .006, after correcting for ARR) and ARR (P = .004, after
      correcting for SBP). In conclusion, most of young-onset HTs are male EHs, and
      aortic valve regurgitation should be carefully checked. Excess plasma renin
      activity would be one of additional characteristics of young-onset EH to male
      gender, genetic background, and increased body mass.

PMID- 21957932
TI  - Positron emission tomography in the diagnostic pathway for intracystic infection
      in adpkd and "cystic" kidneys. a case series.
AB  - BACKGROUND: Intracystic infection, in Autosomal Dominant Polycystic Kidney
      Disease (ADPKD) and in kidneys with multiple cysts, is a diagnostic and
      therapeutic challenge, as conventional imaging techniques may not discriminate
      among "complicated" cysts (infection, bleeding, neoplasia), and as the clinical
      picture may be attenuated, in particular in early phases. Positron Emission
      Tomography with fluorodeoxyglucose (FDG-PET) was recently suggested as a tool to
      detect infection in ADPKD, in single cases and small series.The aim of the study
      was to report on the role of FDG-PET in the work-up of 10 cases of suspected
      cystic infections, affected by ADPKD or with multiple kidney cysts. METHODS:
      Observational study. Review of clinical charts and of the imaging data since the
      use of FDG-PET for detecting cystic infections (2008-2010). RESULTS: In 2008
      2010, 6 patients with ADPKD and 4 with multiple kidney cysts were referred for
      suspected intracystic infections (3 males, 7 females, aged 55-83 years, in all
      CKD stages); in one case the imaging was done in the work-up of a complicated
      "uremic" cyst. The clinical picture, the usual inflammatory markers and/or the
      conventional imaging techniques did not allow conclusive diagnosis at referral or
      during follow-up (ultrasounds in all, CT in 8/10). Nine patients displayed
      inflammatory signs (increase in C-reactive protein and other biochemical markers)
      and constitutional symptoms (fever in 9/10).FDG-PET was positive in 6 cases (5
      kidney and 1 liver cyst), was repeated during follow-up in 4 patients and was
      negative in 4 cases. In the positive cases, FDG-PET guided the therapeutic
      choices; in particular, the duration of therapy was supported by imaging data in
      the 4 cases with multiple scans. No relapse was recorded after discontinuation of
      antibiotic therapy in the treated patients. The negative cases did not develop
      clinical signs of cystic infection over follow-up. CONCLUSION: In this case
      series, the largest prospective one so far published and the only one including
      different types of renal cysts, FDG-PET is confirmed as a promising diagnostic
      tool for detecting intracystic infection in ADPKD and in multiple kidney cysts,
      and a potential guide for tailoring therapy. Further larger and multicenter
      studies are needed to evaluate the cost-benefit ratio and the limits of this
      imaging technique in the clinical setting.

PMID- 21957934
TI  - The AJT Report News and issues that affect organ and tissue transplantation.
AB  - Do accountable care organizations make sense for transplantation? This month,
      "The AJT Report" investigates how this element of healthcare reform may impact
      transplant patient care and clinical practice. Also this month, we look at new
      legislation that hopes to expand immunosuppressant drug coverage, and report on
      findings of a new study focused on risk factors for pediatric heart disease.

PMID- 21957933
TI  - A 3.5-year follow-up of Internet-delivered cognitive behavior therapy for major
      depression.
AB  - BACKGROUND: Internet-delivered cognitive behavior therapy (ICBT) for major
      depression has been tested in several trials, but only with follow-ups up to 1.5
      years. AIM: The aim of this study was to evaluate the outcome of ICBT 3.5 years
      after treatment completion. METHODS: A total of 88 people with major depression
      were randomized to either guided self-help or e-mail therapy in the original
      trial. One-third was initially on a waiting-list. Treatment was provided for
      eight weeks and in this report long-term follow-up data were collected. Also
      included were data from post-treatment and six-month follow-up. A total of 58%
      (51/88) completed the 3.5-year follow-up. Analyses were performed using a random
      effects repeated measures piecewise growth model to estimate trajectory shape
      over time and account for missing data. Results Results showed continued lowered
      scores on the Beck Depression Inventory (BDI). No differences were found between
      the treatment conditions. A large proportion of participants (55%) had sought and
      received additional treatments in the follow-up period. A majority (56.9%) of
      participants had a BDI score lower than 10 at the 3.5-year follow-up.
      CONCLUSIONS: People with mild to moderate major depression may benefit from ICBT
      3.5-years after treatment completion.

PMID- 21957935
TI  - Literature watch implications for transplantation.

PMID- 21957937
TI  - Prevention and control of influenza with vaccines: recommendations of the
      Advisory Committee on Immunization Practices (ACIP), 2011.

PMID- 21957936
TI  - Influenza vaccination in the organ transplant recipient: review and summary
      recommendations.
AB  - Influenza virus causes a spectrum of illness in transplant recipients with a high
      rate of lower respiratory disease. Seasonal influenza vaccination is an important
      public health measure recommended for transplant recipients and their close
      contacts. Vaccine has been shown to be safe and generally well tolerated in both
      adult and pediatric transplant recipients. However, responses to vaccine are
      variable and are dependent on various factors including time from transplantation
      and specific immunosuppressive medication. Seasonal influenza vaccine has
      demonstrated safety and no conclusive evidence exists for a link between
      vaccination and allograft dysfunction. Annually updated trivalent inactivated
      influenza vaccines have been available and routinely used for several decades,
      although newer influenza vaccination formulations including high-dose vaccine,
      adjuvanted vaccine, quadrivalent inactivated vaccine and vaccine by intradermal
      delivery system are now available or will be available in the near future. Safety
      and immunogenicity data of these new formulations in transplant recipients
      requires investigation. In this document, we review the current state of
      knowledge on influenza vaccines in transplant recipients and make recommendations
      on the use of vaccine in both adult and pediatric organ transplant recipients.

PMID- 21957938
TI  - Improving long-term outcomes for transplant patients: making the case for long
      term disease-specific and multidisciplinary research.

PMID- 21957939
TI  - Variability of Heidelberg Retina Tomograph parameters during exercise.
AB  - PURPOSE: The purpose of this study was to determine whether exercise affects the
      stereometric parameters representing optic nerve head (ONH) topography. METHODS:
      ONH topography, intraocular pressure (IOP) and blood pressure of 30 healthy
      volunteers were monitored before, during and after dynamic exercise raising
      systolic blood pressure by a minimum of 30 mmHg. Change in the stereometric ONH
      parameters was calculated. RESULTS: IOP decreased and blood pressure increased
      during exercise, resulting in an increase in mean ocular perfusion pressure.
      Exercise was associated with an increase in variance in 17 of the 18 stereometric
      ONH parameters. The increase in variance was statistically significant in eight
      parameters, including rim area, cup/disc area ratio and cup shape measure. There
      was no statistically significant change in image quality. The absolute change
      from baseline in rim area, cup area, cup/disc area ratio, rim/disc area ratio and
      rim volume showed a statistically significant (p < 0.05) correlation with change
      in mean ocular perfusion pressure. CONCLUSIONS: Exercise increases variability in
      stereometric ONH parameters. To avoid increased variance in the stereometric
      parameters, ONH imaging should be performed after allowing sufficient time to
      rest.

PMID- 21957940
TI  - Application of colour Doppler in encircling constriction of the superficial
      femoral vein in primary deep venous insufficiency of the lower limbs.
AB  - 1. The aim of the present study was to evaluate the clinical value of colour
      Doppler application in encircling constriction of the superficial femoral vein in
      deep vein insufficiency. 2. A total of 87 patients with primary deep venous
      insufficiency (PDVI) using ascending venography were randomly divided into group
      A (44 patients) and group B (43 patients). All patients underwent encircling
      constriction of the superficial femoral vein, high ligation and ablation of the
      great saphenous vein and perforator vein. The duration of venous reflux at
      operation was monitored with colour Doppler in group A (but not group B) to
      evaluate the immediate effects. Clinical grading and scoring of the clinical,
      etiological, anatomical, pathophysiological (CEAP) classification system were
      used to evaluate the follow-up curative effect. 3. In four cases from group A,
      completely destroyed valves were identified at the time of operation and
      autografting of the vein segment with a valve was carried out. The intraoperative
      examination of colour Doppler in group A showed a much shorter duration of vein
      reflux after the encircling constriction procedure than the presurgery condition.
      According to the results of CEAP grading, the success rate of group A (95.0%,
      38/40) was significantly higher than that of group B (76.7%, 33/43).
      Postoperative clinical scores were markedly lower than preoperative scores in
      both groups A and B. 4. In conclusion, our data suggest that application of
      colour Doppler in encircling constriction of superficial femoral vein might
      enhance surgical pertinence and improve surgical effect for PDVI.

PMID- 21957941
TI  - Employing interpersonal influence to promote multivitamin use.
AB  - Boster, Kotowski, Andrews, and Serota (2011 ) proposed that superdiffusers are
      well connected, persuasive, and a maven in a content area. They proposed that
      superdiffusers, if recruited, could promote the adoption of health practices. In
      this article a model of this process is presented, and an intervention designed
      to test the efficacy of this influence strategy is introduced. Specifically,
      superdiffusers were recruited to persuade their peers to take a daily
      multivitamin. Evidence was found consistent with the intervention's
      effectiveness.

PMID- 21957942
TI  - A small molecule inhibitor of Mitf-E-box DNA binding and its depigmenting effect
      in melan-a cells.
AB  - BACKGROUND: Microphthalmia associated transcription factor (Mitf) is a key
      regulatory transcriptional factor of pigmentation-related genes including
      tyrosinase. Inhibition of tyrosinase transcription by blocking the binding of
      Mitf with its promoter E-box DNA can control the pigmentation. However, no such
      chemicals were reported so far. OBJECTIVE: To discover and evaluate the small
      molecule inhibitors of Mitf-E-box DNA. METHODS: Candidate chemicals were screened
      by virtual screening from pharmacophore data followed by Mitf E-box DNA protein
      chip. After selecting the chemical, its inhibitory activity on binding
      interaction between Mitf and E-box DNA, electrophoretic mobility shift assay
      (EMSA) was performed. To evaluate the depigmenting activity of Compound #17,
      cellular melanin assa, and Western blot were performed in melan-a cells. RESULTS:
      Among 27 chemicals selected from a pharmacophore data by virtual screening,
      Compound #17 was screened, which showed the most potent inhibitory activity
      against Mitf-E-box DNA binding in protein chip. EMSA results confirmed the
      specific inhibition of Compound #17 on Mitf-E-box DNA binding. In melan-a cells,
      Compound #17 reduced tyrosinase expression and melanin synthesis (62.5% at 25
      MUM). CONCLUSIONS:   The results show that Compound #17 is the first small
      molecule inhibitor of Mitf-E-box DNA binding with depigmenting activity.

PMID- 21957943
TI  - Influence of electron delocalization in heterocyclic core systems on the
      electrochemical communication in 2,5-di- and 2,3,4,5-tetraferrocenyl thiophenes,
      furans, and pyrroles.
AB  - A series of 2,5-di- and 2,3,4,5-tetraferrocenyl-substituted thiophenes, furans,
      and pyrroles were synthesized using the Negishi C,C cross-coupling protocol. The
      electronic and electrochemical properties of these compounds were investigated by
      cyclic voltammetry (CV), square wave voltammetry (SWV), and in situ UV-vis/NIR
      spectroscopy. The molecular structures of 2,5-diferrocenyl furan and 2,3,4,5
      tetraferrocenyl-1-methyl-1H-pyrrole in the solid state are discussed. The
      ferrocenyls could sequentially be oxidized giving two or four reversible
      responses for the appropriate di- or tetraferrocenyl-substituted heterocyclic
      molecules. The observed DeltaE degrees ' values range between 186 and 450 mV. The
      NIR measurements confirm electronic communication as intervalence charge transfer
      (IVCT) absorptions were found in the corresponding mono- and in case of the
      tetraferrocenyl compounds also in the dicationic species. All compounds, except
      tetraferrocenyl thiophene (a class I system), were classified as class II systems
      according to Robin and Day. They show a linear relationship between DeltaE
      degrees ' and the IVCT oscillator strength f which could be shown for the first
      time in organometallic chemistry. This was possible because the series of
      molecules exhibit analogous geometries and hence, similar electrostatic
      properties. This correlation was confirmed by electro- and spectro
      electrochemical measurements. Within these studies a new approach for the
      estimation of the effective electron transfer distances r(ab) is discussed.

PMID- 21957945
TI  - Introduction to part 2 of the special series on risk regulation.

PMID- 21957946
TI  - Valuing mortality risk reductions from environmental, transport, and health
      policies: a global meta-analysis of stated preference studies.
AB  - We conduct, to our knowledge, the first global meta-analysis (MA) of stated
      preference (SP) surveys of mortality risk valuation. The surveys ask adults their
      willingness to pay (WTP) for small reductions in mortality risks, deriving
      estimates of the sample mean value of statistical life (VSL) for environmental,
      health, and transport policies. We explain the variation in VSL estimates by
      differences in the characteristics of the SP methodologies applied, the
      population affected, and the characteristics of the mortality risks valued,
      including the magnitude of the risk change. The mean (median) VSL in our full
      data set of VSL sample means was found to be around $7.4 million (2.4 million)
      (2005 U.S. dollars). The most important variables explaining the variation in VSL
      are gross domestic product (GDP) per capita and the magnitude of the risk change
      valued. According to theory, however, VSL should be independent of the risk
      change. We discuss and test a range of quality screening criteria in order to
      investigate the effect of limiting the MA to high-quality studies. When limiting
      the MA to studies that find statistically significant differences in WTP using
      external or internal scope tests (without requiring strict proportionality), we
      find that mean VSL from studies that pass both tests tend to be less sensitive to
      the magnitude of the risk change. Mean VSL also tends to decrease when stricter
      screening criteria are applied. For many of our screened models, we find a VSL
      income elasticity of 0.7-0.9, which is reduced to 0.3-0.4 for some subsets of the
      data that satisfy scope tests or use the same high-quality survey.

PMID- 21957947
TI  - The blepharophimosis-ptosis-epicanthus inversus syndrome (BPES).

PMID- 21957948
TI  - Feasibility of using American Joint Committee on Cancer Classification criteria
      for staging eyelid carcinomas.
AB  - PURPOSE:  To evaluate the feasibility of staging eyelid carcinomas using the
      American Joint Committee on Cancer (AJCC) criteria, and to compare the 6(th) and
      7(th) editions. METHODS:  The records of 27 consecutive patients who underwent
      excision of eyelid carcinoma between April 2007 and April 2008 were reviewed.
      Patients with melanoma, lymphoid tumors, nonmeasurable disease, or medial or
      lateral canthal tumors were excluded. Each patient was staged using the AJCC
      6(th) and 7(th) edition criteria based on clinical, pathologic, and radiographic
      data. RESULTS:  The study included 13 men and 14 women aged 32 to 93 years
      (median, 65 years). Seventeen patients had basal cell carcinoma; 3, squamous cell
      carcinoma; 6, sebaceous carcinoma; and 1, Merkel cell carcinoma. Tumor location
      was lower eyelid in 20 patients and upper eyelid in 7. TNM designations were
      reliably determined for all 27 patients and were: A) using the 6(th) edition:
      T1N0M0, 6 patients; T2N0M0, 6; T2N1M0, 1; T3N0M0, 4; T4N0M0, 9; and T4N1M0, 1. B)
      using the 7(th) edition: T1N0M0, 6 patients; T2aN0M0, 8; T2aN1M0, 1; T2bN0M0, 2;
      T3aN0M0, 6; T3aN1M0, 1; T3bN0M0, 2; and T4N0M0, 1. Pathologic tumor size and
      nodal status, and systemic work-up were recorded for all patients. CONCLUSIONS: 
      Eyelid carcinomas can be reliably staged using the AJCC criteria. There are
      notable differences between the 6(th) and 7(th) editions of AJCC TNM designation.
      We recommend AJCC staging using the latest published edition during the initial
      work-up for all patients with eyelid carcinoma to make reporting of outcomes more
      reliable and reproducible.

PMID- 21957950
TI  - Transorbital and transnasal endoscopic repair of a meningoencephalocele.
AB  - A 71-year-old female with a history of thyroid eye disease (TED) presented for
      evaluation of a skull base mass noted on neuroimaging. She had previously
      undergone bilateral orbital decompressions and strabismus surgery and had no
      neurologic symptoms. Successful resection of the menigoencephalocele and repair
      of the skull base defect was performed through a combined transnasal endoscopic
      and transorbital approach, obviating the need for craniotomy.

PMID- 21957949
TI  - Custom ocular prosthesis in children: how often is a change required?
AB  - PURPOSE: To evaluate the indications, outcome and replacement schedule of custom
      ocular prostheses (COP) in children. METHODS: Retrospective review evaluating
      indications, outcome and replacement schedule of COP in children (<=16 years).
      RESULTS: Three hundred and thirty (330) children were fitted with COP. With
      average follow-up of 18.05 months (range 1-50 months), 136(41.2%) children needed
      replacement/modification of the prosthesis. Information regarding indications for
      replacement/modification of prosthesis was available in 125 cases. Indications
      included enophthalmic prosthesis in 34(27.2%), prosthesis rotation within the
      socket in 25(20%), loose fit in 16(12.8%), decentration of the cornea in 15(12%),
      color touch up in 13(10.4%), lost prosthesis in 8(6.4%), cosmetically significant
      ptosis in 2(1.6%), replacement following implant exchange surgery in 2(1.6%) and
      combination of above factors in 10(8%). Time for replacement/modification of
      prosthesis was assessed in 3 age groups. In <=3 years, 47% (36 out of 76)
      children underwent replacement/modification at a mean duration of 18 months
      (range 3-39 months) from the date of prosthesis fitting. In the 3-12 years age
      group, 43% (80 out of 184) underwent replacement/modification at 21 months (range
      2-48 months); and in the 12-16 year age group, 29% (20 out of 70) underwent
      replacement/modification of prosthesis at a mean duration of 26 months (range 3
      50 months). CONCLUSION: A change of prosthesis is required between 18-26 months
      following prosthesis placement in children. Over an average of 18 months, a
      change in the prosthesis was required in 41%, with the youngest age group having
      the highest exchange rate (47%), and the oldest group the lowest (29%).

PMID- 21957951
TI  - Facial asymmetry and nasal septal deviation in acquired nasolacrimal duct
      obstruction.
AB  - INTRODUCTION: Acquired nasolacrimal duct obstruction is a common disorder
      affecting adults. Its pathogenesis is not known. We hypothesize that facial and
      bony asymmetry can contribute to the unilaterality of the nasolacrimal duct
      obstruction. MATERIALS AND METHODS: Retrospective study was done on all patients
      with acquired nasolacrimal duct obstruction who presented to our practice from
      January through June 2010. External photographs were obtained. Lacrimal probing
      and irrigation was used to confirm blockage of the nasolacrimal duct. Nasal
      endoscopy was performed to visualize the intranasal anatomy and location of the
      nasal septum. RESULTS: There were 23 patients who underwent endoscopic
      dacryocystorhinostomy (11 males, 12 females) for acquired nasolacrimal duct
      obstruction. Average age was 58 years old (range, 27 to 84 years). Facial photos
      analysis showed facial asymmetry in 17 patients, with one side being smaller than
      the other side. This corresponded to the side of the nasolacrimal duct
      obstruction in 12 out of these 17 patients (p-value 0.03). Nasal endoscopy
      revealed septal deviation to the side of the nasolacrimal duct obstruction in 21
      of the 23 patients, with one having twisted septal deviation. Septoplasty was
      performed in 10 cases in addition to endoscopic dacryocystorhinostomy.
      CONCLUSIONS: Unilateral nasolacrimal duct obstruction appears to occur on the
      side in which the nasal septum is deviated. There is a trend of nasal septal
      deviation toward the smaller side of the face. Further prospective studies are
      needed to clarify the above relationships.

PMID- 21957952
TI  - Orbital cysticercosis, case report and review.
AB  - Orbital cysticercosis is secondary to an infestation by cysticercus cellulosae,
      the larval form of Taenia solium.Orbital cysticercosis may present with a wide
      spectrum of clinical findings and result in significant ocular morbidity.
      Although traditionally thought to be only prevalent in endemic regions with poor
      sanitation, immigration requires even ophthalmologists practicing in
      industrialised counties to be aware of this masquerading condition's presentation
      and treatment.We report the clinical manifestation of a case of orbital
      cysticersosis that presented with recurrent orbital inflammation for almost a
      year. We also present a literature review of the different ocular manifestations,
      diagnostic and treatment modalities.

PMID- 21957953
TI  - Partial spontaneous cross union post-division of hughes flap.
AB  - We report three cases of partial spontaneous canthal cross union, a rare
      complication in cases where Hughes flaps are used to reconstruct lower eyelid
      defects that also involve the canthi. All cases of spontaneous cross union were
      identified within 2 months of uneventful division of Hughes' flap. Two cases were
      successfully divided with good aesthetic results although one patient was not
      keen on surgery, as it was aesthetically acceptable to him. The postulated
      mechanism was either the proximity of the divided nonepithelial margins or the
      failure to trim the residual upper eyelid tarsoconjunctival remnant. We
      recommended adequate trimming of the residual upper eyelid tarsoconjunctival
      remnant and an early postoperative review to prevent adhesions from developing.

PMID- 21957954
TI  - Isolated bilateral abducens nerve palsy without radiographic etiology and unique
      mechanism of injury.
AB  - Isolated bilateral abducens palsy is a rare event, especially in the setting of
      closed head injury. Cases that lack radiographic or pathologic findings to
      explain the etiology of the palsy are limited to case reports. Injury mechanisms
      have been postulated, but a consensus does not exist. The authors describe a case
      of traumatic isolated bilateral abducens palsy lacking radiographic and
      pathologic findings. A previously unreported potential pathophysiologic injury
      mechanism is theorized based upon anatomical structure and mode of injury.

PMID- 21957955
TI  - Eyelid lesions in lipoid proteinosis or Urbach-Wiethe disease: case report and
      review of the literature.
AB  - Lipoid proteinosis (LP) or Urbach-Wiethe disease is a recessively inherited
      disorder not usually seen by ophthalmologists. It is characterized by non
      inflammatory, persistent papules on the skin and mucous membranes. The first
      clinical manifestation of LP is usually progressive hoarseness. The lid lesions,
      consisting of beaded papules along the lid margins (moniliform blepharosis), are
      considered almost pathognomonic of the disease. The interesting clinical and
      histopathological features of LP are described in a 45-year-old man with a
      history of lipoid proteinosis, who presented to us for evaluation of ocular
      discomfort and unusual multiple eyelid lesions. We surgically removed all the
      eyelid lesions. The histologic findings were consistent with LP. Knowledge of the
      typical eyelid lesions may help to diagnose many typical or atypical cases of LP,
      although biopsy confirmation is always necessary. In our experience, the surgical
      removal of the eyelid lesions seems to be curative and due to the amount of
      eyelid lesions that can be developed, it is recommended to initiate an early
      treatment as soon as possible to avoid postoperative deformities.

PMID- 21957956
TI  - Acute dacryocystitis associated with epstein-barr virus infection.
AB  - Acute dacryocystitis is a rare complication of infectious mononucleosis with only
      three previous reports in the English literature. We present two further children
      with acute dacryocystitis and clinical and laboratory features of Epstein-Barr
      Virus related infectious mononucleosis. Both were treated with systemic
      antibiotics and one child additionally required surgical drainage of a lacrimal
      sac abscess. Both children made a complete recovery without any lacrimal
      symptoms. Acute dacryocystitis is uncommon in children without a history of
      congenital nasolacrimal duct obstruction, and an underlying systemic condition
      such as infectious mononucleosis should be suspected. In such patients,
      dacryocystitis can be expected to resolve without symptoms of nasolacrimal duct
      obstruction and dacryocystorhinostomy is seldom required.

PMID- 21957957
TI  - Periprosthetic bleeding 18 years post-silicone reconstruction of the orbital
      floor.
AB  - BACKGROUND: Periprosthetic orbital haemorrhage is an uncommon complication of the
      alloplastic implants used in post-traumatic orbital floor repair. The small case
      series or individual reports provide no definite causative explanation for this
      delayed bleeding around silicone implants. It is likely that it is related to the
      disruption of fine capillaries within the pseudocapsule surrounding the implant,
      since the material does cause low-grade irritation with evidence of chronic
      inflammation. CASE REPORT: We report the case of a patient who developed a
      spontaneous periprosthetic bleeding 18 years' post-silicone sheet reconstruction
      of the orbital floor. RESULTS: Urgent removal of the implant insured prompt
      resolution of all symptoms and no further problem during the 2-year follow-up.
      CONCLUSION: This report emphasizes that periprosthetic orbital haemorrhage can
      occur years after the initial repair. Awareness of this rare complication allows
      for prompt diagnosis, decreasing the possibility of permanent damage of the
      orbital content. The removal of implant is necessary to relieve the symptoms and
      prevent potential infective complications.

PMID- 21957958
TI  - Temporary Gortex (polytetrafluoroethylene) spacer for the treatment of fornix
      shortening following severe alkali chemical injury.
AB  - BACKGROUND: Gortex is an inert, smooth, flexible material, which is well
      tolerated in situ. We describe a case of fornix shortening secondary to alkali
      injury, which was treated successfully with a temporary Gortex patch. METHOD:
      Retrospective case report. RESULTS: A patient with Grade IV chemical injury
      developed significant symblepharon formation 47 days after the initial injury.
      Following an initial failed mucous membrane graft the patient had a Gortex patch
      sutured into the upper lid fornix which acted as a spacer to allow epithelisation
      of the bulbar conjunctiva. The Gortex patch was removed after 25 days, and at 6
      months' follow-up, there was no recurrence of symblepharon formation. CONCLUSION:
      Industry-related severe ocular chemical injury is a rare occurrence. It can lead
      to symblepharon formation and destruction of the conjunctival fornix. In this
      case a Gortex spacer was successfully used to prevent symblepharon formation and
      reform the upper eyelid fornix after severe chemical injury.

PMID- 21957959
TI  - Basal cell carcinoma in a full-thickness skin graft in the upper eyelid.
AB  - A 75-year-old woman presented with a nodular lesion on a skin graft in her left
      upper eyelid. The lesion had grown gradually over the previous 2 years. She had
      undergone multiple surgeries and full-thickness skin graft procedures 61 years
      previously, because of cutaneous leishmaniasis. The diagnosis of nodular basal
      cell carcinoma was made by means of an excisional biopsy of the lesion. During a
      follow-up period of 27 months, the tumor did not recur. Malignant tumors may
      rarely develop at the site of traumatic or surgical scar. To our knowledge, this
      is the first reported case of basal cell carcinoma arising in a skin graft in the
      eyelid.

PMID- 21957961
TI  - Track structure, radiation quality and initial radiobiological events:
      considerations based on the PARTRAC code experience.
AB  - PURPOSE: The role of track structures for understanding the biological effects of
      radiation has been the subject of research activities for decades. The physics
      that describes such processes is the core Monte Carlo codes, such as the
      biophysical PARTRAC (PARticle TRACks) code described in this review, which follow
      the mechanisms of radiation-matter interaction from the early stage. In this
      paper a review of the track structure theory (and of its possible extension
      concerning non-DNA targets) is presented. MATERIALS AND METHODS: The role of
      radiation quality and track structure is analyzed starting from the heavy ions
      results obtained with the biophysical Monte Carlo code PARTRAC (PARticles
      TRACks). PARTRAC calculates DNA damage in human cells based on the superposition
      of simulated track structures in liquid water to an 'atom-by-atom' model of human
      DNA. RESULTS: Calculations for DNA fragmentation compared with experimental data
      for different radiation qualities are illustrated. As an example, the strong
      dependence of the complexity of DNA damage on radiation track structure, and the
      very large production of very small DNA fragments (lower than 1 kbp (kilo base
      pairs) usually not detected experimentally) after high LET (high-Linear Energy
      Transfer) irradiation is shown. Furthermore the possible importance of non
      nuclear/non-DNA targets is discussed in the particular case of cellular membrane
      and mitochondria. CONCLUSIONS: The importance of the track structure is
      underlined, in particular the dependence of a given late cellular effect on the
      spatial distribution of DNA double-strand breaks (DSB) along the radiation track.
      These results show that the relative biological effectiveness (RBE) for DSB
      production can be significantly larger than 1. Moreover the cluster properties of
      high LET radiation may determine specific initial targets and damage evolution.

PMID- 21957960
TI  - Orbital inflammation in IgG4-related sclerosing disease.
AB  - IgG4-related sclerosing disease is a recently described systemic inflammatory
      disease that should be considered when evaluating patients with nonspecific
      orbital inflammation (pseudotumor). Orbital biopsy is necessary to establish a
      diagnosis and demonstrates lymphoplasmacytic infiltration, fibrosis, obliterative
      phlebitis of medium and small veins, and variable degrees of eosinophilia. We
      report the clinical and histopathological findings of 2 patients who developed
      chronic orbital inflammation as a manifestation of IgG4-related sclerosing
      disease. The 2 cases illustrate the widely varying clinical characteristics of
      this elusive disease.

PMID- 21957962
TI  - Advanced glycation in macrophages induces intracellular accumulation of 7
      ketocholesterol and total sterols by decreasing the expression of ABCA-1 and ABCG
      1.
AB  - BACKGROUND: Advanced glycation end products (AGE) alter lipid metabolism and
      reduce the macrophage expression of ABCA-1 and ABCG-1 which impairs the reverse
      cholesterol transport, a system that drives cholesterol from arterial wall
      macrophages to the liver, allowing its excretion into the bile and feces.
      Oxysterols favors lipid homeostasis in macrophages and drive the reverse
      cholesterol transport, although the accumulation of 7-ketocholesterol, 7alpha-
      hydroxycholesterol and 7beta- hydroxycholesterol is related to atherogenesis and
      cell death. We evaluated the effect of glycolaldehyde treatment (GAD; oxoaldehyde
      that induces a fast formation of intracellular AGE) in macrophages overloaded
      with oxidized LDL and incubated with HDL alone or HDL plus LXR agonist (T0901317)
      in: 1) the intracellular content of oxysterols and total sterols and 2) the
      contents of ABCA-1 and ABCG-1. METHODS: Total cholesterol and oxysterol
      subspecies were determined by gas chromatography/mass spectrometry and HDL
      receptors content by immunoblot. RESULTS: In control macrophages (C), incubation
      with HDL or HDL + T0901317 reduced the intracellular content of total sterols
      (total cholesterol + oxysterols), cholesterol and 7-ketocholesterol, which was
      not observed in GAD macrophages. In all experimental conditions no changes were
      found in the intracellular content of other oxysterol subspecies comparing C and
      GAD macrophages. GAD macrophages presented a 45% reduction in ABCA-1 protein
      level as compared to C cells, even after the addition of HDL or HDL + T0901317.
      The content of ABCG-1 was 36.6% reduced in GAD macrophages in the presence of HDL
      as compared to C macrophages. CONCLUSION: In macrophages overloaded with oxidized
      LDL, glycolaldehyde treatment reduces the HDL-mediated cholesterol and 7
      ketocholesterol efflux which is ascribed to the reduction in ABCA-1 and ABCG-1
      protein level. This may contribute to atherosclerosis in diabetes mellitus.

PMID- 21957964
TI  - Effect of oral diuretics on chronic warfarin therapy: a retrospective study.
AB  - BACKGROUND: Limited clinical documentation is suggestive of a drug interaction
      between warfarin and diuretics. OBJECTIVE: To evaluate the effect on
      international normalized ratio (INR) when a daily oral diuretic is started or
      increased in patients on chronic stable warfarin therapy. METHODS: The medical
      records of all active patients of two hospital-based anticoagulation clinics were
      retrospectively reviewed to identify patients who were started on or received a
      dose increase of a daily oral diuretic while on stable warfarin therapy. The
      primary endpoint was the mean difference between an INR recorded within 30 days
      prior to the diuretic initiation (pre-INR) and an INR recorded within 30 days
      after diuretic initiation (post-INR). RESULTS: A total of 1254 patient charts
      were screened and a total of 123 patients met the study criteria. The mean
      difference in pre-INR and post-INR was 0.09 (95% CI -0.03 to 0.21, p = 0.12).
      Post-INR values were outside of the patient's therapeutic range in 39 patients
      (32%), but no major bleeding or thromboembolic events were reported. CONCLUSION:
      Based on this retrospective study, diuretics did not result in a significant
      change in the INR in patients on stable warfarin therapy.

PMID- 21957965
TI  - Stochastic amperometric fluctuations as a probe for dynamic adsorption in
      nanofluidic electrochemical systems.
AB  - Adsorption of analyte molecules is ubiquitous in nanofluidic channels due to
      their large surface-to-volume ratios. It is also difficult to quantify due to the
      nanometric scale of these channels. We propose a simple method to probe dynamic
      adsorption at electrodes that are embedded in nanofluidic channels or which
      enclose nanoscopic volumes. The amperometric method relies on measuring the
      amplitude of the fluctuations of the redox cycling current that arise when the
      channel is diffusively coupled to a bulk reservoir. We demonstrate the
      versatility of this new method by quantifying adsorption for several redox
      couples, investigating the dependence of adsorption on the electrode potential
      and studying the effect of functionalizing the electrodes with self-assembled
      monolayers of organothiol molecules bearing polar end groups. These self
      assembled monolayer coatings are shown to significantly reduce the adsorption of
      the molecules on to the electrodes. The detection method is not limited to
      electrodes in nanochannels and can be easily extended to redox cycling systems
      that enclose very small volumes, in particular scanning electrochemical
      microscopy with nanoelectrodes. It thus opens the way for imaging spatial
      heterogeneity with respect to adsorption, as well as rational design of
      interfaces for redox cycling based sensors.

PMID- 21957966
TI  - The enzymatic activities of the Escherichia coli basic aliphatic amino acid
      decarboxylases exhibit a pH zone of inhibition.
AB  - The stringent response regulator ppGpp has recently been shown by our group to
      inhibit the Escherichia coli inducible lysine decarboxylase, LdcI. As a follow-up
      to this observation, we examined the mechanisms that regulate the activities of
      the other four E. coli enzymes paralogous to LdcI: the constitutive lysine
      decarboxylase LdcC, the inducible arginine decarboxylase AdiA, the inducible
      ornithine decarboxylase SpeF, and the constitutive ornithine decarboxylase SpeC.
      LdcC and SpeC are involved in cellular polyamine biosynthesis, while LdcI, AdiA,
      and SpeF are involved in the acid stress response. Multiple mechanisms of
      regulation were found for these enzymes. In addition to LdcI, LdcC and SpeC were
      found to be inhibited by ppGpp; AdiA activity was found to be regulated by
      changes in oligomerization, while SpeF and SpeC activities were regulated by GTP.
      These findings indicate the presence of multiple mechanisms regulating the
      activity of this important family of decarboxylases. When the enzyme inhibition
      profiles are analyzed in parallel, a "zone of inhibition" between pH 6 and pH 8
      is observed. Hence, the data suggest that E. coli utilizes multiple mechanisms to
      ensure that these decarboxylases remain inactive around neutral pH possibly to
      reduce the consumption of amino acids at this pH.

PMID- 21957972
TI  - On the culture-independent assessment of the diversity and distribution of
      Prochlorococcus.
AB  - Much of our current knowledge on Prochlorococcus has derived from research on
      various genetic strains that have successfully been brought into culture. In
      particular, analyses of the complete genomes of 12 of those isolates have
      revealed the extent to which these strains differ from each other and the genetic
      means by which they are adapted to specific environmental niches. However, based
      on culture-independent studies it is now clear that the strains currently
      available in diverse culture collections do not represent the true diversity of
      Prochlorococcus geno- and phenotypes. Potential alternatives to overcome the
      limitations caused by difficulties in isolating Prochlorococcus may be provided
      by the whole-genome amplification of flow cytometrically isolated individual
      cells. The new information obtained in this way on various genetic types would,
      in turn, facilitate the correct identification of Prochlorococcus-derived
      sequences within metagenomic sequence data sets. However, culture-independent
      molecular population genetic approaches have also greatly furthered our
      understanding of the ecology and physiological capability of Prochlorococcus
      genetic groups. Based on this, I support the notion that such population genetic
      approaches to reveal the Prochlorococcus microdiversity are still of great value
      if appropriate marker genes providing a high genetic resolution are used. The
      comparison of the results from those culture-independent analyses of
      environmental marine samples with those from the measurement of relevant
      environmental and biotic parameters still has potential to uncover further
      parameters that control Prochlorococcus diversity and distribution. In this
      context, I will discuss those markers that have so far been used in population
      genetic studies of Prochlorococcus, which is followed by outlining a general
      approach to evaluate their use for resolving microbial microdiversity and for
      phylogenetic identification.

PMID- 21957974
TI  - Phosphine-catalyzed Heine reaction.
AB  - Aziridines are important synthetic intermediates which readily undergo ring
      opening reactions. It is demonstrated that electron-rich phosphines are efficient
      catalysts for the regioselective rearrangement of N-acylaziridines to oxazolines.
      The reactions occur in excellent yield under neutral conditions. Evidence is
      provided for an addition/elimination mechanism by generation of a phosphonium
      intermediate. Similar intermediates may be useful for the development of
      alternate aziridine ring-opening processes and stereoselective synthesis with
      enantiopure phosphines.

PMID- 21957973
TI  - Metal allergy and second-generation metal-on-metal arthroplasties.
AB  - There are concerns about the induction of metal allergy with second-generation
      metal-on-metal prostheses, and the role that this may play in the development of
      complications such as 'pseudotumours' or failure of the implant. In this review,
      we attempt to set out the current knowledge on this subject. From a review of the
      literature, it is apparent that the first-generation metal-on-metal replacement
      hips did cause metal sensitization, and that joint failure was associated with
      this, although it is still not clear which one led to the other. Highly
      engineered second-generation metal-on-metal arthroplasties used in joint
      resurfacings are now increasingly employed. Several studies have recently shown
      an association between metal sensitization and peri-implant hypersensitivity
      reactions and implant loosening and failure, although the overall risk appears to
      be low. The pragmatic approach adopted by most contact dermatologists for
      patients known to be allergic to nickel, cobalt or chromium and who require joint
      replacement is to recommend prostheses made of titanium-based alloys. Patch
      testing continues to be a useful tool as laboratory investigations for metal
      hypersensitivity continue to emerge. The development of guidelines on the
      management of patients receiving metal-on-metal arthroplasties suspected of being
      metal-allergic is desirable.

PMID- 21957975
TI  - Monitoring bisphosphonate surface functionalization and acid stability of
      hierarchically porous titanium zirconium oxides.
AB  - To take advantage of the full potential of functionalized transition metal
      oxides, a well-understood nonsilane based grafting technique is required. The
      functionalization of mixed titanium zirconium oxides was studied in detail using
      a bisphosphonic acid, featuring two phosphonic acid groups with high surface
      affinity. The bisphosphonic acid employed was coupled to a UV active benzamide
      moiety in order to track the progress of the surface functionalization in situ.
      Using different material compositions, altering the pH environment, and looking
      at various annealing conditions, key features of the functionalization process
      were identified that consequently will allow for intelligent material design.
      Loading with bisphosphonic acid was highest on supports calcined at 650  degrees
      C compared to lower calcination temperatures: A maximum capacity of 0.13 mmol g(
      1) was obtained and the adsorption process could be modeled with a pseudo-second
      order rate relationship. Heating at 650  degrees C resulted in a phase transition
      of the mixed binary oxide to a ternary oxide, titanium zirconium oxide in the
      srilankite phase. This phase transition was crucial in order to achieve high
      loading of the bisphosphonic acid and enhanced chemical stability in highly
      acidic solutions. Due to the inert nature of phosphorus-oxygen-metal bonds,
      materials functionalized by bisphosphonic acids showed increased chemical
      stability compared to their nonfunctionalized counterparts in harshly acidic
      solutions. Leaching studies showed that the acid stability of the functionalized
      material was improved with a partially crystalline srilankite phase. The
      materials were characterized using nitrogen sorption, X-ray powder diffraction,
      and UV-vis spectroscopy; X-ray photoelectron spectroscopy was used to study
      surface coverage with the bisphosphonic acid molecules.

PMID- 21957976
TI  - The effects of simvastatin on left ventricular hypertrophy and left ventricular
      function in patients with essential hypertension.
AB  - This study is to evaluate the effects of Simvastatin on left ventricular
      hypertrophy and left ventricular function in patients with essential
      hypertension. Untreated or noncompliance with drug treatment patients with simple
      essential hypertension were treated with a therapy on the basis of using
      Telmisartan to decrease blood pressure (BP). There were 237 patients who had
      essential hypertension combined with left ventricular hypertrophy as diagnosed by
      echocardiography, taken after their BPs were decreased to meet the values of the
      standard normal. Among them, there were only 41 out of the original 237 patients,
      17.3%, who had simple essential hypertension combined with left ventricular
      hypertrophy without any other co-existing disease. They were the patients
      selected for this study. All patients were randomly, indiscriminately divided
      into two groups: one was the control group (Group T), treated with the
      Telmisartan-based monotherapy; the other was the target group (Group TS), treated
      with the Telmisartan-based plus simvastatin therapy. The changes of left
      ventricular hypertrophy and left ventricular function were rediagnosed by
      echocardiography after 1 year. The results we obtained from this study were as
      follows: (i) The average BPs at the beginning of the study, of simple essential
      hypertension combined with left ventricular hypertrophy, were high levels
      (systolic blood pressure (SBP) 189.21 +/- 19.91 mm Hg, diastolic blood pressure
      101.40 +/- 16.92 mm Hg). (ii) The Telmisartan-based plus simvastatin therapy was
      significantly effective in lowering the SBP (128.26 +/- 9.33 mm Hg vs. 139.22 +/-
      16.34 mm Hg). (iii) After the 1-year treatment, the parameters of left
      ventricular hypertrophy in both groups were improved. Compared to group T, there
      were no differences in the characteristics of the subjects, including
      interventricular septum, left ventricular mass, left ventricular mass index,
      ejection fraction, left atrium inner diameter at baseline. The patients'
      interventricular septum (Group TS 10.30 +/- 1.80 mm vs. Group T 10.99 +/- 1.68
      mm, P < .05), LVM (Group TS 177.43 +/- 65.40 g vs. Group T 181.28 +/- 65.09 g, P
      < .05), and LVMI (Group TS 100.97 +/- 37.33 g/m(2) vs. Group T 106.54 +/- 27.95
      g/m(2), P < .05), all dropped more prominently (P < .05) in group TS; the
      ejection fraction rose more remarkably in group TS (Group TS: 57.50 +/- 16.41% to
      65.43 +/- 11.60%, P < .01 while showing no change in Group T); the left
      ventricular hypertrophy reversed more significantly and the left ventricular
      systolic function improved more. (iv) The left atrium inner diameter of Group TS
      decreased (P < .01), the ratio of E/A, which indicates the left ventricular
      diastolic function, continued to drop further, showing no change to the trend of
      left ventricular diastolic function declination. Patients who have hypertension
      with left ventricular hypertrophy usually suffer other accompanying diseases at
      the same time. Telmisartan-based plus Simvastatin treatment can significantly
      reduce SBP, reverse left ventricular hypertrophy, improve the left ventricular
      systolic function, but it has no effect on reversing the left ventricular
      diastolic function. This experiment indicated that Simvastatin can reverse left
      ventricular hypertrophy and improve left systolic function.

PMID- 21957978
TI  - Generalized pustular psoriasis-like eruptions induced after the first use of
      adalimumab in the treatment of psoriatic arthritis.

PMID- 21957977
TI  - CD44 isoforms are heterogeneously expressed in breast cancer and correlate with
      tumor subtypes and cancer stem cell markers.
AB  - BACKGROUND: The CD44 cell adhesion molecule is aberrantly expressed in many
      breast tumors and has been implicated in the metastatic process as well as in the
      putative cancer stem cell (CSC) compartment. We aimed to investigate potential
      associations between alternatively spliced isoforms of CD44 and CSCs as well as
      to various breast cancer biomarkers and molecular subtypes. METHODS: We used q-RT
      PCR and exon-exon spanning assays to analyze the expression of four alternatively
      spliced CD44 isoforms as well as the total expression of CD44 in 187 breast
      tumors and 13 cell lines. ALDH1 protein expression was determined by IHC on TMA.
      RESULTS: Breast cancer cell lines showed a heterogeneous expression pattern of
      the CD44 isoforms, which shifted considerably when cells were grown as
      mammospheres. Tumors characterized as positive for the CD44+/CD24- phenotype by
      immunohistochemistry were associated to all isoforms except the CD44 standard
      (CD44S) isoform, which lacks all variant exons. Conversely, tumors with strong
      expression of the CSC marker ALDH1 had elevated expression of CD44S. A high
      expression of the CD44v2-v10 isoform, which retain all variant exons, was
      correlated to positive steroid receptor status, low proliferation and luminal A
      subtype. The CD44v3-v10 isoform showed similar correlations, while high
      expression of CD44v8-v10 was correlated to positive EGFR, negative/low HER2
      status and basal-like subtype. High expression of CD44S was associated with
      strong HER2 staining and also a subgroup of basal-like tumors. Unsupervised
      hierarchical cluster analysis of CD44 isoform expression data divided tumors into
      four main clusters, which showed significant correlations to molecular subtypes
      and differences in 10-year overall survival. CONCLUSIONS: We demonstrate that
      individual CD44 isoforms can be associated to different breast cancer subtypes
      and clinical markers such as HER2, ER and PgR, which suggests involvement of CD44
      splice variants in specific oncogenic signaling pathways. Efforts to link CD44 to
      CSCs and tumor progression should consider the expression of various CD44
      isoforms.

PMID- 21957979
TI  - Superoxide dismutase 3 suppresses hyaluronic acid fragments mediated skin
      inflammation by inhibition of toll-like receptor 4 signaling pathway: superoxide
      dismutase 3 inhibits reactive oxygen species-induced trafficking of toll-like
      receptor 4 to lipid rafts.
AB  - AIMS: Hyaluronic acid (HA) is a component of the extracellular matrix and has
      been extensively applied for cosmetic, therapeutic, and antiaging purposes.
      However, HA fragments (HAFs) cause adverse effects. Considering that UV-exposure
      produces HAF that accumulated on the skin, the role of HAF in skin inflammation
      and its precise mechanism needs to be clarified, and strategies for the
      prevention of skin inflammation are necessary. RESULTS: We found that
      extracellular superoxide dismutase (SOD), SOD3, suppresses HAF-mediated skin
      inflammation, while HAF mediated skin inflammation, macrophages and dendritic
      cells (DCs) dominantly infiltrate, up-regulating inflammatory cytokines and
      chemokines receptors. However, keratinocytes indirectly responded to HAF.
      Instead, epidermis containing keratinocytes were stimulated by secreted molecules
      from HAF-treated macrophages or DC and produced inflammatory molecules including
      chemokines, which, in turn, led to skin inflammation. This orchestrated
      inflammatory response was inhibited by SOD3. In addition, SOD3 inhibited DC
      maturation by suppressing the expression of major histocompatibility complex II,
      CD80, and CD86. Interestingly, these responses did not occur in Toll-like
      receptor 4 (TLR4) deficient mice. Similar to lipopolysaccharide (LPS), HAF
      promoted TLR4 translocation into the lipid rafts to initiate signaling. This
      trafficking was mediated, at least in part, by NAPDH oxidase-dependent reactive
      oxygen species (ROS) generation. Subsequently, nuclear factor kappa B (NFkappaB)
      subunit, p65, was recruited the promoters of genes encoding inflammatory
      molecules. This inflammatory machinery was blocked by SOD3. INNOVATION AND
      CONCLUSION: Thus, we propose that SOD3 might provide an effective strategy for
      the treatment of HAF-mediated skin inflammation.

PMID- 21957980
TI  - A genetic pathway for tapetum development and function in Arabidopsis.
AB  - In anther development, tapetal cells take part in complex processes, including
      endomitosis and apoptosis (programmed cell death). The tapetum provides many of
      the proteins, lipids, polysaccharides and other molecules necessary for pollen
      development. Several transcription factors, including DYT1, TDF1, AMS, MS188 and
      MS1, have been reported to be essential for tapetum development and function in
      Arabidopsis thaliana. Here, we present a detailed cytological analysis of
      knockout mutants for these genes, along with an in situ RNA hybridization
      experiment and double mutant analysis showing that these transcription factors
      form a genetic pathway in tapetum development. DYT1, TDF1 and AMS function in
      early tapetum development, while MS188 and MS1 are important for late tapetum
      development. The genetic pathway revealed in this work facilitates further
      investigation of the function and molecular mechanisms of tapetum development in
      Arabidopsis.

PMID- 21957981
TI  - caCORRECT2: Improving the accuracy and reliability of microarray data in the
      presence of artifacts.
AB  - BACKGROUND: In previous work, we reported the development of caCORRECT, a novel
      microarray quality control system built to identify and correct spatial artifacts
      commonly found on Affymetrix arrays. We have made recent improvements to
      caCORRECT, including the development of a model-based data-replacement strategy
      and integration with typical microarray workflows via caCORRECT's web portal and
      caBIG grid services. In this report, we demonstrate that caCORRECT improves the
      reproducibility and reliability of experimental results across several common
      Affymetrix microarray platforms. caCORRECT represents an advance over state-of
      art quality control methods such as Harshlighting, and acts to improve gene
      expression calculation techniques such as PLIER, RMA and MAS5.0, because it
      incorporates spatial information into outlier detection as well as outlier
      information into probe normalization. The ability of caCORRECT to recover
      accurate gene expressions from low quality probe intensity data is assessed using
      a combination of real and synthetic artifacts with PCR follow-up confirmation and
      the affycomp spike in data. The caCORRECT tool can be accessed at the website:
      http://cacorrect.bme.gatech.edu. RESULTS: We demonstrate that (1) caCORRECT's
      artifact-aware normalization avoids the undesirable global data warping that
      happens when any damaged chips are processed without caCORRECT; (2) When used
      upstream of RMA, PLIER, or MAS5.0, the data imputation of caCORRECT generally
      improves the accuracy of microarray gene expression in the presence of artifacts
      more than using Harshlighting or not using any quality control; (3) Biomarkers
      selected from artifactual microarray data which have undergone the quality
      control procedures of caCORRECT are more likely to be reliable, as shown by both
      spike in and PCR validation experiments. Finally, we present a case study of the
      use of caCORRECT to reliably identify biomarkers for renal cell carcinoma,
      yielding two diagnostic biomarkers with potential clinical utility, PRKAB1 and
      NNMT. CONCLUSIONS: caCORRECT is shown to improve the accuracy of gene expression,
      and the reproducibility of experimental results in clinical application. This
      study suggests that caCORRECT will be useful to clean up possible artifacts in
      new as well as archived microarray data.

PMID- 21957982
TI  - Surgical outcome in children undergoing hypospadias repair under caudal epidural
      vs penile block.
AB  - AIM AND OBJECTIVE:   To evaluate the effect of penile block vs caudal epidural on
      the quality of analgesia and surgical outcome following hypospadias repair.
      BACKGROUND:   Intraoperative penile engorgement because of caudal epidural may
      result in tension on surgical sutures and alter surgical outcome. METHODS:  
      Fifty-four ASA I and II children were randomly allocated to group P (penile
      block, 0.25% bupivacaine, 0.5 mg.kg(-1) ; n = 27) and group C (caudal epidural,
      0.25% bupivacaine, 0.5 ml.kg(-1) ; n = 27), respectively. Quality of analgesia
      was assessed by visual analog scale (VAS) score recorded at 0, 0.5, 3, 6, 12, 24
      h, and once a day for the next 4 days. Duration of analgesia was calculated from
      the institution of block to the first analgesic demand by child or VAS > 5. Total
      morphine consumption in the first 48 h and oral paracetamol consumption till 5th
      day were recorded. Children were regularly followed up in their respective
      outpatient clinic for early or late complications. RESULTS:   In group P, lower
      mean VAS scores were seen from 0.5 h after surgery till day 3 and analgesia
      lasted for significantly longer duration (82 min) when compared with caudal
      epidural, P < 0.001. Incidence of urethral fistula formation after primary
      hypospadias repair was 19.2%, and all had received caudal epidural. An increase
      of 27% in penile volume from baseline value was observed 10 min after caudal
      epidural placement, P < 0.05. CONCLUSION:   Penile block provided better
      analgesia when compared with caudal epidural in children undergoing primary
      hypospadias repair. Postoperative urethral fistula formation was more likely in
      children who received caudal epidural.

PMID- 21957983
TI  - Influenza vaccination: the persuasiveness of messages among people aged 65 years
      and older.
AB  - About 90% of all influenza-related deaths occur among people aged 65 years and
      older. Vaccination remains the primary option for preventing influenza infection.
      This study examined the efficacy of messages designed to increase the uptake of
      influenza vaccination. Two messages, narrative and didactic, were created based
      on the Extended Parallel Process Model (EPPM). The study employed a one-factor
      between-subjects experimental design with participants assigned randomly to three
      conditions: no message, didactic communication, and narrative communication.
      Participants were 311 Italian people aged 65 years or older. The results showed
      that, compared to no message and didactic communication, narrative communication
      was related to higher risk perception of influenza, to higher perception of the
      efficacy of the vaccine, and to self-efficacy related to vaccination, controlling
      for social trust, previous flu shot, and demographic variables. There were no
      differences among the three conditions with respect to the intention to receive
      the influenza vaccine. Findings suggest that narrative communication based on
      EPPM may have a persuasive effect on people aged 65 years or older.

PMID- 21957984
TI  - Thermochromic luminescence of copper iodide clusters: the case of phosphine
      ligands.
AB  - Three copper(I) iodide clusters coordinated by different phosphine ligands
      formulated [Cu(4)I(4)(PPh(3))(4)] (1), [Cu(4)I(4)(Pcpent(3))(4)] (2), and
      [Cu(4)I(4)(PPh(2)Pr)(4)] (3) (PPh(3) = triphenylphosphine, Pcpent(3) =
      tricyclopentylphosphine, and PPh(2)Pr = diphenylpropylphosphine) have been
      synthesized and characterized by (1)H and (31)P NMR, elemental analysis and
      single crystal X-ray diffraction analysis. They crystallize in different space
      groups, namely, monoclinic P21/c, cubic Pa 3, and tetragonal I 42m for 1, 2, and
      3, respectively. The photoluminescence properties of clusters 1 and 3 show
      reversible luminescence thermochromism with two highly intense emission bands
      whose intensities are temperature dependent. In accordance to Density Functional
      Theory (DFT) calculations, these two emission bands have been attributed to two
      different transitions, a cluster centered (CC) one and a mixed XMCT/XLCT one.
      Cluster 2 does not exhibit luminescence variation in temperature because of the
      lack of the latter transition. The absorption spectra of the three clusters have
      been also rationalized by time dependent DFT (TDDFT) calculations. A simplified
      model is suggested to represent the luminescence thermochromism attributed to the
      two different excited states in thermal equilibrium. In contrast with the
      pyridine derivatives, similar excitation profiles and low activation energy for
      these phosphine-based clusters reflect high coupling of the two emissive states.
      The effect of the Cu-Cu interactions on the emission properties of these clusters
      is also discussed. Especially, cluster 3 with long Cu-Cu contacts exhibits a
      controlled thermochromic luminescence which is to our knowledge, unknown for this
      family of copper iodide clusters. These phosphine-based clusters appear
      particularly interesting for the synthesis of original emissive materials.

PMID- 21957986
TI  - High-temperature vaporization of B2O3(l) under reducing conditions.
AB  - The vaporization of B(2)O(3) in a reducing environment leads to the formation of
      both B(2)O(3)(g) and B(2)O(2)(g). Whereas the formation of B(2)O(3)(g) is well
      understood, many questions about the formation of B(2)O(2)(g) remain. Previous
      studies using B(s) + B(2)O(3)(l) have led to inconsistent thermodynamic data. In
      this study, it was found that, after heating, B(s) and B(2)O(3)(l) appeared to
      separate and variations in contact area likely led to the inconsistent vapor
      pressures of B(2)O(2)(g). To circumvent this problem, the activity of boron was
      fixed with a two-phase mixture of FeB and Fe(2)B. Both second- and third-law
      enthalpies of formation were measured for B(2)O(2)(g) and B(2)O(3)(g). From these
      values, the enthalpies of formation at 298.15 K were calculated to be -479.9 +/-
      25.7 kJ/mol for B(2)O(2)(g) and -833.4 +/- 13.1 kJ/mol for B(2)O(3)(g). Ab initio
      calculations to determine the enthalpies of formation of B(2)O(2)(g) and
      B(2)O(3)(g) were conducted using the W1BD composite method and showed good
      agreement with the experimental values.

PMID- 21957985
TI  - A risk assessment model for enterotoxigenic Staphylococcus aureus in pasteurized
      milk: a potential route to source-level inference.
AB  - This article describes a probabilistic model that quantifies hazards that arise
      from Staphylococcus aureus in milk that is sold as pasteurized in the United
      Kingdom. The model is centered on coupled dynamics for S. aureus populations,
      staphylococcal enterotoxins, and the concentration of alkaline phosphatase
      throughout the milk chain. The chain includes farm collection and storage of
      pooled milk, further pooling for off-farm processing, high temperature short time
      thermal processing, and possible postprocess contamination. The model is
      implemented as a Bayesian belief network. The results indicate that milk sold as
      pasteurized is relatively safe with respect to the hazards associated with S.
      aureus and that most risk is associated with small scale on-farm processing. An
      additional analysis of likelihood ratios shows that alkaline phosphatase
      concentrations in filler tank milk are a good indicator of potential hazards and
      that these concentrations, in conjunction with other measurements, can be used
      effectively to discriminate over possible failure modes. The ability to
      discriminate over potential failure modes can support preemptive actions, such as
      maintenance or hygiene, which assist with milk chain management and, over
      extended periods, accumulate to drive improved safety, efficiency, and security.

PMID- 21957987
TI  - Evidence for an encounter expectancy bias in fear of spiders.
AB  - Whereas research has demonstrated that phobic or fearful individuals overestimate
      the likelihood of incurring aversive consequences from an encounter with feared
      stimuli, it has not yet been systematically investigated whether these
      individuals also overestimate the likelihood (i.e., the frequency) of such
      encounters. In the current study, spider-fearful and control participants were
      presented with background information that allowed them to estimate the overall
      likelihood that different kinds of animals (spiders, snakes, or birds) would be
      encountered. Spider-fearful participants systematically overestimated the
      likelihood of encountering a spider with respect to the likelihood of
      encountering a snake or a bird. No such expectancy bias was observed in control
      participants. The results thus strengthen our idea that there indeed exist two
      different types of expectancy bias in high fear and phobia that can be related to
      different components of the fear response. A conscientious distinction and
      examination of these two types of expectancy bias are of potential interest for
      therapeutic applications.

PMID- 21957988
TI  - An implementation to read and write IAEA phase-space files in GEANT4-based
      simulations.
AB  - PURPOSE: To develop a stand-alone code to make any application coded with the
      GEANT4 (GEometry ANd Tracking, version 4) toolkit capable of reading and writing
      phase-space (phsp) files in the format created by the IAEA (International Atomic
      Energy Agency), so that the exchange of phsp files between other validated Monte
      Carlo (MC) codes and GEANT4 is possible. METHODS: We present a stand-alone code,
      written in C++ object-oriented language, developed in a way that ensures the
      compatibility with future versions of the IAEA phsp format. The aim of the reader
      part is to get the information from a given IAEA phsp file and create the primary
      particles in a GEANT4 user application. On the other hand, the writer part of the
      code is the responsible for writing the IAEA phsp files during a run of the
      GEANT4 application. RESULTS: A testing simulation was written with GEANT4 to
      verify the performance of this code, with satisfactory results. An example of use
      in a GEANT4 application which simulates the treatment head of a radiotherapy
      linear electron accelerator (linac) is also shown, comparing dose calculations
      with experimental data. CONCLUSIONS: This stand-alone package, which can be used
      in any GEANT4 application, allows the exchange of validated phsp files between
      different MC codes and the use of phsp data from many different accelerators and
      fields in dosimetry studies. Furthermore, it also offers additional utilities of
      interest in medical applications.

PMID- 21957989
TI  - Computationally efficient marginal models for clustered recurrent event data.
AB  - Large observational databases derived from disease registries and retrospective
      cohort studies have proven very useful for the study of health services
      utilization. However, the use of large databases may introduce computational
      difficulties, particularly when the event of interest is recurrent. In such
      settings, grouping the recurrent event data into prespecified intervals leads to
      a flexible event rate model and a data reduction that remedies the computational
      issues. We propose a possibly stratified marginal proportional rates model with a
      piecewise-constant baseline event rate for recurrent event data. Both the absence
      and the presence of a terminal event are considered. Large-sample distributions
      are derived for the proposed estimators. Simulation studies are conducted under
      various data configurations, including settings in which the model is
      misspecified. Guidelines for interval selection are provided and assessed using
      numerical studies. We then show that the proposed procedures can be carried out
      using standard statistical software (e.g., SAS, R). An application based on
      national hospitalization data for end-stage renal disease patients is provided.

PMID- 21957990
TI  - A label-free quantitative shotgun proteomics analysis of rice grain development.
AB  - BACKGROUND: Although a great deal of rice proteomic research has been conducted,
      there are relatively few studies specifically addressing the rice grain proteome.
      The existing rice grain proteomic researches have focused on the identification
      of differentially expressed proteins or monitoring protein expression patterns
      during grain filling stages. RESULTS: Proteins were extracted from rice grains
      10, 20, and 30 days after flowering, as well as from fully mature grains. By
      merging all of the identified proteins in this study, we identified 4,172 non
      redundant proteins with a wide range of molecular weights (from 5.2 kDa to 611
      kDa) and pI values (from pH 2.9 to pH 12.6). A Genome Ontology category
      enrichment analysis for the 4,172 proteins revealed that 52 categories were
      enriched, including the carbohydrate metabolic process, transport, localization,
      lipid metabolic process, and secondary metabolic process. The relative abundances
      of the 1,784 reproducibly identified proteins were compared to detect 484
      differentially expressed proteins during rice grain development. Clustering
      analysis and Genome Ontology category enrichment analysis revealed that proteins
      involved in the metabolic process were enriched through all stages of
      development, suggesting that proteome changes occurred even in the desiccation
      phase. Interestingly, enrichments of proteins involved in protein folding were
      detected in the desiccation phase and in fully mature grain. CONCLUSION: This is
      the first report conducting comprehensive identification of rice grain proteins.
      With a label free shotgun proteomic approach, we identified large number of rice
      grain proteins and compared the expression patterns of reproducibly identified
      proteins during rice grain development. Clustering analysis, Genome Ontology
      category enrichment analysis, and the analysis of composite expression profiles
      revealed dynamic changes of metabolisms during rice grain development.
      Interestingly, we detected that proteins involved in glycolysis, TCA-cycle, lipid
      metabolism, and proteolysis accumulated at higher levels in fully mature grain
      compared to grain developing stages, suggesting that the accumulation of these
      proteins during the desiccation stage may be associated with the preparation of
      proteins required in germination.

PMID- 21957991
TI  - Translational research to realize the full potential of novel agents--an
      opportunity for vinflunine?
AB  - In the past few years, innumerable novel anti-cancer agents have been developed.
      Some of them have successfully entered into clinical practice while some of them
      have failed for different reasons. Although, nowadays, cancer treatment still
      relies heavily on conventional chemotherapy and surgery, with increasing evidence
      of novel biologic agents which demonstrate its higher anti-cancer activity and
      fewer side effects, more and more efforts have been spent on development of
      different types of novel agents. Vinflunine, a novel fluorinated vinca alkaloid,
      carries mitotic-arresting and tubulin-interacting properties and was just
      approved for treating transitional cell carcinoma of the urothelial tract (TCCU)
      in Europe. It, however, took quite a long time to get an approval. Needless to
      say, TCCU, similar to other types of cancer, is a very complex and heterogeneous
      disease and therefore, a single drug can hardly eradicate a cancer. Translational
      research, a new scientific research method, creates a link between clinical and
      laboratory studies. The link helps us to investigate the change in tumor
      environment in response to treatment, select patients who are more responsive to
      a particular treatment and predict prognosis of a group of patients with similar
      tumor characteristics. It can not only improve the success of a treatment, but
      also maximize the potential of novel anti-cancer agents.

PMID- 21957992
TI  - Sub-10 nm hexagonal lanthanide-doped NaLuF4 upconversion nanocrystals for
      sensitive bioimaging in vivo.
AB  - By thermal decomposition in the presence only of oleylamine, sub-10 nm hexagonal
      NaLuF(4)-based nanocrystals codoped with Gd(3+), Yb(3+), and Er(3+) (or Tm(3+))
      have been successfully synthesized. Sub-10 nm beta-NaLuF(4): 24 mol % Gd(3+), 20
      mol % Yb(3+), 1 mol % Tm(3+) nanocrystals display bright upconversion
      luminescence (UCL) with a quantum yield of 0.47 +/- 0.06% under continuous-wave
      excitation at 980 nm. Furthermore, through the use of beta
      NaLuF(4):Gd(3+),Yb(3+),Tm(3+) nanocrystals as a luminescent label, the detection
      limit of <50 nanocrystal-labeled cells was achieved for whole-body
      photoluminescent imaging of a small animal (mouse), and high-contrast UCL imaging
      of a whole-body black mouse with a penetration depth of ~2 cm was achieved.

PMID- 21957995
TI  - Novel insights into the biotin carboxylase domain reactions of pyruvate
      carboxylase from Rhizobium etli.
AB  - The catalytic mechanism of the MgATP-dependent carboxylation of biotin in the
      biotin carboxylase domain of pyruvate carboxylase from R. etli (RePC) is common
      to the biotin-dependent carboxylases. The current site-directed mutagenesis study
      has clarified the catalytic functions of several residues proposed to be pivotal
      in MgATP-binding and cleavage (Glu218 and Lys245), HCO(3)(-) deprotonation
      (Glu305 and Arg301), and biotin enolization (Arg353). The E218A mutant was
      inactive for any reaction involving the BC domain and the E218Q mutant exhibited
      a 75-fold decrease in k(cat) for both pyruvate carboxylation and the full reverse
      reaction. The E305A mutant also showed a 75- and 80-fold decrease in k(cat) for
      both pyruvate carboxylation and the full reverse reaction, respectively. While
      Glu305 appears to be the active site base which deprotonates HCO(3)(-), Lys245,
      Glu218, and Arg301 are proposed to contribute to catalysis through substrate
      binding interactions. The reactions of the biotin carboxylase and carboxyl
      transferase domains were uncoupled in the R353M-catalyzed reactions, indicating
      that Arg353 may not only facilitate the formation of the biotin enolate but also
      assist in coordinating catalysis between the two spatially distinct active sites.
      The 2.5- and 4-fold increase in k(cat) for the full reverse reaction with the
      R353K and R353M mutants, respectively, suggests that mutation of Arg353 allows
      carboxybiotin increased access to the biotin carboxylase domain active site. The
      proposed chemical mechanism is initiated by the deprotonation of HCO(3)(-) by
      Glu305 and concurrent nucleophilic attack on the gamma-phosphate of MgATP. The
      trianionic carboxyphosphate intermediate formed reversibly decomposes in the
      active site to CO(2) and PO(4)(3-). PO(4)(3-) then acts as the base to
      deprotonate the tethered biotin at the N(1)-position. Stabilized by interactions
      between the ureido oxygen and Arg353, the biotin-enolate reacts with CO(2) to
      give carboxybiotin. The formation of a distinct salt bridge between Arg353 and
      Glu248 is proposed to aid in partially precluding carboxybiotin from reentering
      the biotin carboxylase active site, thus preventing its premature decarboxylation
      prior to the binding of a carboxyl acceptor in the carboxyl transferase domain.

PMID- 21957996
TI  - Hypersensitivity reactions to metallic implants - diagnostic algorithm and
      suggested patch test series for clinical use.
AB  - Cutaneous and systemic hypersensitivity reactions to implanted metals are
      challenging to evaluate and treat. Although they are uncommon, they do exist, and
      require appropriate and complete evaluation. This review summarizes the evidence
      regarding evaluation tools, especially patch and lymphocyte transformation tests,
      for hypersensitivity reactions to implanted metal devices. Patch test evaluation
      is the gold standard for metal hypersensitivity, although the results may be
      subjective. Regarding pre-implant testing, those patients with a reported history
      of metal dermatitis should be evaluated by patch testing. Those without a history
      of dermatitis should not be tested unless considerable concern exists. Regarding
      post-implant testing, a subset of patients with metal hypersensitivity may
      develop cutaneous or systemic reactions to implanted metals following implant.
      For symptomatic patients, a diagnostic algorithm to guide the selection of
      screening allergen series for patch testing is provided. At a minimum, an
      extended baseline screening series and metal screening is necessary. Static and
      dynamic orthopaedic implants, intravascular stent devices, implanted
      defibrillators and dental and gynaecological devices are considered. Basic
      management suggestions are provided. Our goal is to provide a comprehensive
      reference for use by those evaluating suspected cutaneous and systemic metal
      hypersensitivity reactions.

PMID- 21957998
TI  - Aryl aldehydes as traceless dielectrophiles in bifunctional titanocene-catalyzed
      propargylic C-X activations.
AB  - The titanocene-catalyzed construction of all-carbon substituted tertiary centers
      directly from aromatic aldehydes is described. The starting aldehyde behaves as a
      traceless functionality in the formation of multiple carbon-carbon bonds through
      consecutive carbon-heteroatom bond activations. The sequential addition of a
      metal acetylide and a second carbon nucleophile to the dielectrophilic aldehyde
      enables the construction of symmetrical and unsymmetrical 1,4-diynes in good
      yields.

PMID- 21957999
TI  - Income and education as predictors of return to working life among younger stroke
      patients.
AB  - BACKGROUND: Socioeconomic conditions are not only related to poor health
      outcomes, they also contribute to the chances of recovery from stroke. This study
      examines whether income and education were predictors of return to work after a
      first stroke among persons aged 40-59. METHODS: All first-stroke survivors aged
      40-59 who were discharged from a hospital in 1996-2000 and who had received
      income from work during the year prior to the stroke were sampled from the
      Swedish national register of in-patient care (n = 7,081). Income and education
      variables were included in hazard regressions, modelling the probability of
      returning to work from one to four years after discharge. Adjustments for age,
      sex, stroke subtype, and length of in-patient care were included in the models.
      RESULTS: Both higher income and higher education were associated with higher
      probability of returning to work. While the association between education and
      return to work was attenuated by income, individuals with university education
      were 13 percent more likely to return than those who had completed only
      compulsory education, and individuals in the highest income quartile were about
      twice as likely to return as those in the lowest. The association between
      socioeconomic position and return to work was similar for different stroke
      subtypes. Income differences between men and women also accounted for women's
      lower probability of returning to work. CONCLUSIONS: The study demonstrates that
      education and income were independent predictors of returning to work among
      stroke patients during the first post-stroke years. Taking the relative risk of
      return to work among those in the higher socioeconomic positions as the
      benchmark, there may be considerable room for improvement among patients in lower
      socioeconomic strata.

PMID- 21958000
TI  - Successful treatment with infliximab for refractory pyoderma gangrenosum
      associated with inflammatory bowel disease.

PMID- 21957997
TI  - Hematologic profile of the fetus with systemic inflammatory response syndrome.
AB  - OBJECTIVE: The fetal inflammatory response syndrome (FIRS) is associated with
      impending onset of preterm labor/delivery, microbial invasion of the amniotic
      cavity and increased perinatal morbidity. FIRS has been defined by an elevated
      fetal plasma interleukin (IL)-6, a cytokine with potent effects on the
      differentiation and proliferation of hematopoietic precursors. The objective of
      this study was to characterize the hematologic profile of fetuses with FIRS.
      STUDY DESIGN: Fetal blood sampling was performed in patients with preterm
      prelabor rupture of membranes and preterm labor with intact membranes (n=152). A
      fetal plasma IL-6 concentration >= 11 pg/mL was used to define FIRS. Hemoglobin
      concentration, platelet count, total white blood cell (WBC) count, differential
      count, and nucleated red blood cell (NRBC) count were obtained. Since blood cell
      count varies with gestational age, the observed values were corrected for fetal
      age by calculating a ratio between the observed and expected mean value for
      gestational age. RESULTS: 1) The prevalence of FIRS was 28.9% (44/152); 2)
      fetuses with FIRS had a higher median corrected WBC and corrected neutrophil
      count than those without FIRS (WBC: median 1.4, range 0.3-5.6, vs. median 1.1,
      range 0.4-2.9, P=0.001; neutrophils: median 3.6, range 0.1-57.5, vs. median 1.8,
      range 0.2-13.9, P<0.001); 3) neutrophilia (defined as a neutrophil count >95th
      centile of gestational age) was significantly more common in fetuses with FIRS
      than in those without FIRS (71%, 30/42, vs. 35%, 37/105; P<0.001); 4) more than
      two-thirds of fetuses with FIRS had neutrophilia, whereas neutropenia was present
      in only 4.8% (2/42); 5) FIRS was not associated with detectable changes in
      hemoglobin concentration, platelet, lymphocyte, monocyte, basophil or eosinophil
      counts; and 6) fetuses with FIRS had a median corrected NRBC count higher than
      those without FIRS. However, the difference did not reach statistical
      significance (NRBC median 0.07, range 0-1.3, vs. median 0.04, range 0-2.3,
      P=0.06). CONCLUSION: The hematologic profile of the human fetus with FIRS is
      characterized by significant changes in the total WBC and neutrophil counts. The
      NRBC count in fetuses with FIRS tends to be higher than fetuses without FIRS.

PMID- 21958001
TI  - Beneficial effect of switching from a combination of angiotensin II receptor
      blockers other than losartan and thiazides to a fixed dose of
      losartan/hydrochlorothiazide on uric acid metabolism in hypertensive patients.
AB  - Among the angiotensin II receptor blockers (ARBs), losartan (LOS) has uricosuric
      action. The clinical benefits of LOS compared with those of other ARBs may be
      apparent when it is combined with diuretics, which have an unfavorable influence
      on serum uric acid (SUA). The effects of switching from combinations of ARBs
      other than LOS and thiazides to a fixed-dose combination comprising 50 mg LOS and
      12.5 mg hydrochlorothiazide on blood pressure (BP), SUA, percent fractional
      excretion of UA (FEUA), and urine pH were assessed in 57 hypertensive
      outpatients. A significant reduction in BP was observed after 6 months (P < .01).
      The switching therapy significantly decreased SUA level (6.0 +/- 1.3 vs. 5.7 +/-
      1.3 mg/dL, P < .01), which was accompanied by increases in FEUA (P < .01) and
      urine pH (P < .01). The change in SUA was negatively correlated with the changes
      in FEUA (P < .004) and estimated glomerular filtration rate (P < .05). The change
      in FEUA was positively correlated with the changes in urine pH (P < .05) but not
      with BP or estimated glomerular filtration rate. In a separate group of patients
      treated with ARBs other than LOS (n = 82), a significant BP reduction was
      observed, but no change in SUA or FEUA was observed. In conclusion, switching
      therapy decreased SUA level, which was accompanied by an increase in FEUA. This
      result may depend on the balance between LOS-induced inhibitory action of urate
      transporter 1 and hydrochlorothiazide-induced plasma volume reduction. The
      increase in urine pH plays a role in UA urinary excretion.

PMID- 21958002
TI  - Effect of growth hormone treatment on pancreatic inflammation, oxidative stress,
      and apoptosis related to aging in SAMP8 mice.
AB  - Aging is associated with an increase in inflammation, oxidative stress, and
      apoptosis. Furthermore, aging is accompanied by an alteration of the growth
      hormone (GH) -insulin-like growth factor-1 (IGF-1) axis. The aim of this study
      was to examine the regulation of these parameters in the pancreas of old mice and
      how GH treatment could affect this process. Male senescence-accelerated prone
      mice (SAMP8) and male senescence-accelerated resistant mice (SAMR1) 2 (young) and
      10 months old were used (n = 40). Animals were divided into five experimental
      groups: 1 and 2, SAMP8/R1 young control; 3 and 4, SAMP8/R1 old control
      (untreated); and 5, SAMP8 old treated with GH. Physiologically equivalent doses
      of GH were administered for 1 month (2 mg subcutaneously [s.c.]/kg/day) and
      several parameters were analyzed. Aging was associated with increased
      inflammation, oxidative stress, and apoptosis (increased tumor necrosis factor
      alpha [TNF-alpha], interleukin-beta [IL-beta], IL-6, monocyte chemoattractant
      protein-1 [MCP1], IL-2, heme oxygenase [HO-1], inducible nitric oxide synthase
      [iNOS], and nitric oxide metabolites [NOx]). The ratio of anti/pro apoptotic mRNA
      expression-B cell lymphoma 2 (Bcl-2) Bcl-2-associated X protein (BAX) + Bcl
      xL/Bcl-2-associated death promoter (BAD)-was decreased during aging in SAMP8
      mice. X-inhibitor of apoptosis (XIAP) was decreased during the aging process.
      Furthermore, no changes were observed in protein expression of nuclear factor
      kappaB (NF-kappaB p65 and NF-kappaBp50-105. However, the protein expression of NF
      kappaB p52-100 and inhibitor kappa B (IkappaB) alpha was increased with age in
      the pancreas of SAMP8 mice. On the other hand, the expression of IkappaB beta was
      decreased with aging. These results indicate that aging is associated with
      significant alterations in the relative expression of pancreatic genes involved
      in inflammation, oxidative stress, and apoptosis. According to our results, GH
      administration to old SAMP8 mice was able to improve pancreas from this
      parameters.

PMID- 21958003
TI  - The genetics of the human APOE polymorphism.
AB  - Abstract   The genetic origin of the three common variants of the human
      apolipoprotein E (apoE) protein, known as E2, E3 and E4, was understood in 1981,
      and since the mid 1980s these are probably the most-studied protein variants in
      human races. They have been related to a number of age-related diseases,
      including Alzheimer disease, as well as to healthy aging and longevity. The gene
      variants underlying these protein isoforms, known as epsilon2, epsilon3, and
      epsilon4, are allelic forms of the APOE gene, resulting from different haplotypes
      at the APOE locus (19q13.31). In particular, they result from three of the four
      haplotypes expected by the combinations of the alleles of the two single
      nucleotide polymorphisms rs429358 and rs7412. The fourth missing haplotype, known
      as epsilon3r, has been identified in only two Caucasian families from Italy and
      in one Yoruba family from Nigeria worldwide. Thus, this fourth APOE gene variant
      is rare, and it encodes a protein isoform, identified as E3r, showing identical
      physical characteristics to E3, that conversely, is the most common form of apoE
      in humans. In this review article, we report the identification of the haplotype
      epsilon3r in a third Caucasian family from Italy, and then attempt to re-examine
      the current knowledge regarding the APOE polymorphism, taking into account this
      fourth haplotype. We also focus on the commonly accepted hypothesis for the
      evolution of the common APOE gene variants, in which we include the epsilon3r
      haplotype, previously not considered.

PMID- 21958004
TI  - A polyorchid dog.
AB  - The case of a polyorchid Irish Setter is presented here. Castration and intra
      abdominal testis removal were performed one year of age when one scrotal and one
      cryptorchid testis near the right inguinal canal were removed. Later it became
      apparent that there was still testosterone production. A third testis, abdominal
      cryptorchid, was found on the right side cranially and right to the bladder. The
      third testis had a strong cranial suspensory ligament and the tail of the
      epididymis was elongated. The ductus deferens did not enter the prostate but
      followed the gubernaculum to the inguinal canal near the stump of the previous
      operation on the caudal right testis. This suggests that two right cryptorchid
      testes had common ductus deferens.

PMID- 21958005
TI  - Multilocus association mapping using generalized ridge logistic regression.
AB  - BACKGROUND: In genome-wide association studies, it is widely accepted that
      multilocus methods are more powerful than testing single-nucleotide polymorphisms
      (SNPs) one at a time. Among statistical approaches considering many predictors
      simultaneously, scan statistics are an effective tool for detecting
      susceptibility genomic regions and mapping disease genes. In this study, inspired
      by the idea of scan statistics, we propose a novel sliding window-based method
      for identifying a parsimonious subset of contiguous SNPs that best predict
      disease status. RESULTS: Within each sliding window, we apply a forward model
      selection procedure using generalized ridge logistic regression for model fitness
      in each step. In power simulations, we compare the performance of our method with
      that of five other methods in current use. Averaging power over all the
      conditions considered, our method dominates the others. We also present two
      published datasets where our method is useful in causal SNP identification.
      CONCLUSIONS: Our method can automatically combine genetic information in local
      genomic regions and allow for linkage disequilibrium between SNPs. It can
      overcome some defects of the scan statistics approach and will be very promising
      in genome-wide case-control association studies.

PMID- 21958006
TI  - Thermometric sensing of nitrofurantoin by noncovalently imprinted polymers
      containing two complementary functional monomers.
AB  - Molecularly imprinted polymers (MIPs) for nitrofurantoin (NFT) recognition
      addressing in parallel of two complementary functional groups were created using
      a noncovalent imprinting approach. Specific tailor-made functional monomers were
      synthesized: a diaminopyridine derivative as the receptor for the imide residue
      and three (thio)urea derivatives for the interaction with the nitro group of NFT.
      A significantly improved binding of NFT to the new MIPs was revealed from the
      imprinting factor, efficiency of binding, affinity constants and maximum binding
      number as compared to previously reported MIPs, which addressed either the imide
      or the nitro residue. Substances possessing only one functionality (either the
      imide group or nitro group) showed significantly weaker binding to the new
      imprinted polymers than NFT. However, the compounds lacking both functionalities
      binds extremely weak to all imprinted polymers. The new imprinted polymers were
      applied in a flow-through thermistor in organic solvent for the first time. The
      MIP-thermistor allows the detection of NFT down to a concentration of 5 MUM in
      acetonitrile + 0.2% dimethyl sulfoxide (DMSO). The imprinting factor of 3.91 at
      0.1 mM of NFT as obtained by thermistor measurements is well comparable to the
      value obtained by batch binding experiments.

PMID- 21958007
TI  - Molecular dynamics study of surfactin monolayer at the air/water interface.
AB  - The surface parameter of protonated surfactin molecules and the structural
      properties of the protonated surfactin monolayer adsorbed at the air/water
      interface have been studied by molecular dynamics simulation. The simulation was
      performed at 293 K and the interfacial concentration of surfactin was set in a
      range of 0.70-2.20 nm(2) molecule(-1). The results show that the interfacial
      concentration greatly affects the molecular orientation of surfactin, the
      structure of the peptide ring backbone and the spatial arrangement of the
      surfactin monolayer. The peptide ring backbone of the surfactin molecule exhibits
      a structural flexibility, and a more packed structure is adopted at higher
      interfacial concentration. The hydrophobic contacts between surfactin molecules
      and the stability of the secondary structures, beta-turn structure in Leu2 ->
      Asp5 and the beta-sheet domains, are enhanced when the surfactin molecules are in
      a very packed situation.

PMID- 21958009
TI  - Vasoconstrictor and vasodilator responses to tryptamine of rat-isolated perfused
      mesentery: comparison with tyramine and beta-phenylethylamine.
AB  - BACKGROUND AND PURPOSE: Tryptamine increases blood pressure by vasoconstriction,
      but little is known about its actions on the mesentery, in particular the
      resistance arteries. Tryptamine interacts with trace amine-associated receptors
      (TAARs) and because of its structural similarity to 5-HT, it may also interact
      with 5-HT receptors. Our hypothesis is therefore that the rat mesenteric arterial
      bed will exhibit vasopressor and vasodepressor responses to tryptamine via both 5
      HT and TAARs. EXPERIMENTAL APPROACH: Tryptamine-evoked responses were assayed
      from pressure changes of the rat-isolated mesenteric vasculature perfused at
      constant flow rate in the absence and presence of adrenoceptor and 5-HT receptor
      antagonists. KEY RESULTS: Tryptamine caused dose-dependent vasoconstriction of
      the mesenteric arterial bed as increases in perfusion pressure. These were
      unaffected by the alpha(1) -adrenoceptor antagonist, prazosin, but were
      attenuated by the non-selective alpha-adrenoceptor antagonist, phentolamine. The
      5-HT(2A) receptor antagonists, ketanserin and ritanserin, abolished the
      tryptamine-induced pressure increases to reveal vasodilator responses in
      mesenteric beds preconstricted with phenylephrine. These tryptamine-induced
      vasodilator responses were unaffected by the 5-HT(7) receptor antagonist,
      SB269970, but were eliminated by the NOS inhibitor, N(omega) -nitro-L-arginine
      methyl ester (L-NAME). Tyramine and beta-phenylethylamine also caused
      vasodilatation in pre-constricted vasculature, which was also abolished by L
      NAME. CONCLUSIONS AND IMPLICATIONS: Tryptamine causes vasoconstriction of the
      mesenteric vasculature via 5-HT(2A) receptors, which when inhibited exposed
      vasorelaxant effects in pre-constricted tissues. The vasodilatation was
      independent of 5-HT(2A) and 5-HT(7) receptors but like that for tyramine and beta
      phenylethylamine was due to NO release. Potency orders suggest TAAR involvement
      in the vasodilatation by these trace amines.

PMID- 21958010
TI  - Investigating the validity of a structured interview protocol for assessing the
      preferences of children with autism spectrum disorders.
AB  - PURPOSE: To investigate the congruent validity of a structured interview protocol
      for assessing the preferences of seven children with autism spectrum disorder
      (ASD). METHOD: Using the structured interview protocol described by Green et al.,
      parents were asked to provide a rank ordering of their child's preferred foods,
      drinks, toys and sensory stimuli. The resulting rank order was then compared to
      the results of a multiple-stimulus without replacement preference assessment by
      calculating the Spearman rank order correlation coefficients. RESULTS: The
      results revealed a high level of correspondence between the rank orderings of
      both assessments for four of the six participants for food and drink items and
      four of the seven participants for play items and sensory stimuli. CONCLUSION:
      Results support the use of the structured interview protocol to determine the
      preferences of children with ASD. Practical implications and directions for
      future research are discussed.

PMID- 21958008
TI  - A review of methods used in assessing non-serious adverse drug events in
      observational studies among type 2 diabetes mellitus patients.
AB  - Clinical drug trials are often conducted in selective patient populations, with
      relatively small numbers of patients, and a short duration of follow-up.
      Observational studies are therefore important for collecting additional
      information on adverse drug events (ADEs). Currently, there is no guidance
      regarding the methodology for measuring ADEs in such studies. Our aim was to
      evaluate whether the methodology used to assess non-serious ADEs in observational
      studies is adequate for detecting these ADEs, and for addressing limitations from
      clinical trials in patients with type 2 diabetes mellitus. We systematically
      searched MEDLINE and EMBASE for observational studies reporting non-serious ADEs
      (1999-2008). Methods to assess ADEs were classified as: 1) medical record review;
      2) surveillance by health care professionals (HCP); 3) patient survey; 4)
      administrative data; 5) laboratory/clinical values; 6) not specified. We compared
      the range of ADEs identified, number and selection of patients included, and
      duration of follow-up. Out of 10,125 publications, 68 studies met our inclusion
      criteria. The most common methods were based on laboratory/clinical values (n =
      25) and medical record review (n = 18). Solicited surveillance by HCP (n = 17)
      revealed the largest diversity of ADEs. Patient surveys (n = 15) focused mostly
      on hypoglycaemia and gastrointestinal ADEs, laboratory values based studies on
      hepatic and metabolic ADEs, and administrative database studies (n = 5) on
      cardiovascular ADEs. Four studies presented ADEs that were identified with the
      use of more than one method. The patient population was restricted to a lower
      risk population in 19% of the studies. Less than one third of the studies
      exceeded pre-approval regulatory requirements for sample size and duration of
      follow-up. We conclude that the current assessment of ADEs is hampered by the
      choice of methods. Many observational studies rely on methods that are inadequate
      for identifying all possible ADEs. Patient-reported outcomes and combinations of
      methods are underutilized. Furthermore, while observational studies often include
      unselective patient populations, many do not adequately address other limitations
      of pre-approval trials. This implies that these studies will not provide
      sufficient information about ADEs to clinicians and patients. Better protocols
      are needed on how to assess adverse drug events not only in clinical trials but
      also in observational studies.

PMID- 21958011
TI  - Frustrated Lewis pairs beyond the main group: synthesis, reactivity, and small
      molecule activation with cationic zirconocene-phosphinoaryloxide complexes.
AB  - The extension of the frustrated Lewis pair (FLP) concept to the transition series
      with cationic zirconocene-phosphinoaryloxide complexes is demonstrated. Such
      complexes mimic the reactivity of main group FLPs in reactions such as
      heterolytic hydrogen cleavage, CO(2) activation, olefin and alkyne addition, and
      ring-opening of tetrahydrofuran. The interplay between sterics and electronics is
      shown to have an important role in determining the reactivity of these compounds
      with hydrogen in particular. The Zr-H species generated from the heterolytic
      activation of hydrogen is shown to undergo insertion reactions with both CO(2)
      and CO. Crucially, these transition metal FLPs are markedly more reactive than
      main group systems in many cases, and in addition to the usual array of reactions
      they demonstrate unprecedented reactivity in the activation of small molecules.
      This includes S(N)2 and E2 reactions with alkyl chlorides and fluorides, enolate
      formation from acetone, and the cleavage of C-O bonds to facilitate S(N)2 type
      reactions with noncyclic dialkyl ethers.

PMID- 21958012
TI  - Effect of increased nursing home hospice use on nursing assistant staffing.
AB  - BACKGROUND: Since 1999, there has been a significant increase in hospice
      providers and hospice use in nursing homes. A 1997 Office of Inspector General
      (OIG) report warned of possible kickbacks, monetary and otherwise, that might be
      paid by hospices to nursing homes in exchange for referrals. One possible
      kickback mentioned in the report was nursing homes receiving additional staff
      hours at no cost, which could lead to decreases in nursing home staffing. The
      purpose of this study was to determine if changes in nursing home hospice volume
      were related to changes in certified nursing assistant (CNA) staffing. METHODS:
      The study included free-standing nursing homes with at least 3 years of
      observation between 1999 and 2006, no fewer than five deaths in any year, and
      between 30 and 500 beds (n=10,759). We examined the longitudinal relationship
      between changing hospice volume and CNA minutes per resident day (MPRD),
      utilizing nursing home fixed-effects regression analysis and adjusting for
      resident case mix and changing organizational characteristics. RESULTS: The
      introduction of hospice services in a nursing home did not result in
      statistically significant changes in CNA staffing. Instead, increases in hospice
      volume resulted in small increases in CNA staffing. Specifically, the addition of
      1000 hospice days, in a given year, resulted in an additional 0.79 (95%
      confidence interval [CI] 0.373-1.211) CNA MPRD. CONCLUSIONS: The proposition that
      nursing homes may be decreasing their staffing as a result of receiving
      additional hospice staff was not supported by this study and, in fact, nursing
      homes were found to only slightly increase CNA staffing with increasing hospice
      volume.

PMID- 21958017
TI  - Towards a taxonomy of Bacteria and Archaea based on interactive and cumulative
      data repositories.
AB  - Taxonomy in the second decade of the 21st century is benefiting from
      technological advances in molecular microbiology, especially those related to
      genomics. Gene and genome databases are significantly increasing due to intense
      research activities in the field of molecular ecology and genomics. Taxa, and
      especially species, are tailored by means of the recognition of a phylogenetic,
      genomic and phenotypic coherence that reveal their uniqueness in the
      classification schema. Phylogenetic coherence is mainly revealed by means of 16S
      rRNA gene analyses for which curated databases such as EzTaxon and LTP provide a
      valuable tool for tree reconstruction to taxonomy users. On the other hand, in
      silico full or partial genomic sequence comparisons are called on to substitute
      cumbersome techniques such as DNA-DNA hybridization (DDH) to genomically
      circumscribe species. DDH similarity values around 70% would be equivalent to ANI
      values of 96%. Finally, finding an exclusive phenotypic property for the taxa to
      be classified is of paramount relevance to producing an operative and predictive
      classification system. The current methods used for taxonomic classification
      require significant laboratory experimentation, and generally will not produce
      interactive databases. The new high-throughput metabolomic technologies, such as
      ICR-FT and MALDI-TOF mass spectrometry methods, open the door to the construction
      of metabolic databases for taxonomic purposes. It is to be foreseen that, in the
      future, taxonomists will benefit significantly from public databases speeding up
      the classification process. However, serious effort will be needed to harmonize
      them and to prevent inaccurate material.

PMID- 21958016
TI  - Interaction between the biotin carboxyl carrier domain and the biotin carboxylase
      domain in pyruvate carboxylase from Rhizobium etli.
AB  - Pyruvate carboxylase (PC) catalyzes the ATP-dependent carboxylation of pyruvate
      to oxaloacetate, an important anaplerotic reaction in mammalian tissues. To
      effect catalysis, the tethered biotin of PC must gain access to active sites in
      both the biotin carboxylase domain and the carboxyl transferase domain. Previous
      studies have demonstrated that a mutation of threonine 882 to alanine in PC from
      Rhizobium etli renders the carboxyl transferase domain inactive and favors the
      positioning of biotin in the biotin carboxylase domain. We report the 2.4 A
      resolution X-ray crystal structure of the Rhizobium etli PC T882A mutant which
      reveals the first high-resolution description of the domain interaction between
      the biotin carboxyl carrier protein domain and the biotin carboxylase domain. The
      overall quaternary arrangement of Rhizobium etli PC remains highly asymmetrical
      and is independent of the presence of allosteric activator. While biotin is
      observed in the biotin carboxylase domain, its access to the active site is
      precluded by the interaction between Arg353 and Glu248, revealing a mechanism for
      regulating carboxybiotin access to the BC domain active site. The binding
      location for the biotin carboxyl carrier protein domain demonstrates that
      tethered biotin cannot bind in the biotin carboxylase domain active site in the
      same orientation as free biotin, helping to explain the difference in catalysis
      observed between tethered biotin and free biotin substrates in biotin carboxylase
      enzymes. Electron density located in the biotin carboxylase domain active site is
      assigned to phosphonoacetate, offering a probable location for the putative
      carboxyphosphate intermediate formed during biotin carboxylation. The insights
      gained from the T882A Rhizobium etli PC crystal structure provide a new series of
      catalytic snapshots in PC and offer a revised perspective on catalysis in the
      biotin-dependent enzyme family.

PMID- 21958018
TI  - Exposure to wet work in working Australians.
AB  - BACKGROUND: The Australian National Hazard Exposure Worker Surveillance (NHEWS)
      Survey 2008 was a cross-sectional survey undertaken by Safe Work Australia to
      inform the development of exposure prevention initiatives for occupational
      disease. This is a descriptive study of workplace exposures. OBJECTIVES: To
      assess the occupational and demographic characteristics of workers reporting
      exposure to wet work. METHODS: Computer-assisted telephone interviews were
      conducted with 4500 workers. Two wet work exposure outcomes (frequent washing of
      hands and duration of time spent at work with the hands immersed in liquids) were
      analysed. RESULTS: The response rate for the study was 42.3%. For hand-washing,
      9.8% [95% confidence interval (CI) 8.9-10.7] reported washing their hands more
      than 20 times per day. For immersion of hands in liquids, 4.5% (95% CI 3.9-5.1)
      reported immersion for more than 2 hr per day. Females were more likely to report
      exposure to frequent hand-washing than males [odds ratio (OR) 1.97, 95% CI 1.49
      2.61]. Workers in the lowest occupational skill level jobs were more likely to
      report increased exposure to hands immersed in liquids than those in the highest
      (OR 6.41, 95% CI 3.78-10.88). Workers reporting skin exposure to chemicals were
      more likely to report exposure to hand-washing (OR 3.68, 95% CI 2.91-4.66) and
      immersion of the hands in liquids (OR 4.09, 95% CI 2.92-5.74). CONCLUSIONS:
      Specific groups of workers reported high levels of exposure to wet work. There
      were differences between the profiles of workers reporting frequent hand-washing
      and workers reporting increased duration of exposure to hands immersed in
      liquids. We also found a high correlation between wet work and chemical exposure.

PMID- 21958019
TI  - A trial of a job-specific workers' health surveillance program for construction
      workers: study protocol.
AB  - BACKGROUND: Dutch construction workers are offered periodic health examinations.
      This care can be improved by tailoring this workers health surveillance (WHS) to
      the demands of the job and adjust the preventive actions to the specific health
      risks of a worker in a particular job. To improve the quality of the WHS for
      construction workers and stimulate relevant job-specific preventive actions by
      the occupational physician, we have developed a job-specific WHS. The job
      specific WHS consists of modules assessing both physical and psychological
      requirements. The selected measurement instruments chosen, are based on their
      appropriateness to measure the workers' capacity and health requirements. They
      include a questionnaire and biometrical tests, and physical performance tests
      that measure physical functional capabilities. Furthermore, our job-specific WHS
      provides occupational physicians with a protocol to increase the worker
      behavioural effectiveness of their counselling and to stimulate job-specific
      preventive actions. The objective of this paper is to describe and clarify our
      study to evaluate the behavioural effects of this job-specific WHS on workers and
      occupational physicians. METHODS/DESIGN: The ongoing study of bricklayers and
      supervisors is a nonrandomised trial to compare the outcome of an intervention
      (job-specific WHS) group (n = 206) with that of a control (WHS) group (n = 206).
      The study includes a three-month follow-up. The primary outcome measure is the
      proportion of participants who have undertaken one or more of the preventive
      actions advised by their occupational physician in the three months after
      attending the WHS. A process evaluation will be carried out to determine context,
      reach, dose delivered, dose received, fidelity, and satisfaction. The present
      study is in accordance with the TREND Statement. DISCUSSION: This study will
      allow an evaluation of the behaviour of both the workers and occupational
      physician regarding the preventive actions undertaken by them within the scope of
      a job-specific WHS. TRIAL REGISTRATION: NTR3012.

PMID- 21958020
TI  - Atypical pityriasis rosea in a pregnant woman: first report associating local
      herpes simplex virus 2 reactivation.

PMID- 21958021
TI  - Experimental burial inhibits methanogenesis and anaerobic decomposition in water
      saturated peats.
AB  - A mechanistic understanding of carbon (C) sequestration and methane (CH(4))
      production is of great interest due to the importance of these processes for the
      global C budget. Here we demonstrate experimentally, by means of column
      experiments, that burial of water saturated, anoxic bog peat leads to
      inactivation of anaerobic respiration and methanogenesis. This effect can be
      related to the slowness of diffusive transport of solutes and evolving energetic
      constraints on anaerobic respiration. Burial lowered decomposition constants in
      homogenized peat sand mixtures from about 10(-5) to 10(-7) yr(-1), which is
      considerably slower than previously assumed, and methanogenesis slowed down in a
      similar manner. The latter effect could be related to acetoclastic methanogenesis
      approaching a minimum energy quantum of -25 kJ mol(-1) (CH(4)). Given the
      robustness of hydraulic properties that locate the oxic-anoxic boundary near the
      peatland surface and constrain solute transport deeper into the peat, this effect
      has likely been critical for building the peatland C store and will continue
      supporting long-term C sequestration in northern peatlands even under moderately
      changing climatic conditions.

PMID- 21958022
TI  - Versatile introduction of azido moiety into oligonucleotides through diazo
      transfer reaction.
AB  - The use of a diazo transfer (DZT) reagent enables clean and efficient conversion
      of aminated oligodeoxyribonucleotides (ODNs) into their azido counterparts under
      mild conditions. ODNs bearing an amino tether at the 3', 5', or any internal
      position could be modified in this manner thus demonstrating the versatility of
      this reaction. Easy access to such azido-modified ODNs is of great interest for
      conjugation in particular through copper catalyzed 1,3-dipolar cycloaddition
      (CuAAC reaction).

PMID- 21958023
TI  - Cardiovascular and metabolic safety profiles of the fluoroquinolones.
AB  - INTRODUCTION: Certain fluoroquinolones share similar indications of use. A
      comparison among Cardiovascular and metabolic (i.e., dysglycemia) safety profiles
      of the fluoroquinolones might be particularly useful for the prescribers'
      decision-making process as well as to hypothesize future researcher purposes.
      AREAS COVERED: A literature search was conducted using keywords apt to identify
      information on safety profile of the fluoroquinolones. Publications concerned
      with descriptive and etiological surveys were manually reviewed. EXPERT OPINION:
      Cardiac alterations and blood glucose impairments might be associated with any
      fluoroquinolone. However, the benefit/risk profile of these agents could be
      stratified for the single compounds. Several predisposing factors, such as
      diabetes, heart illnesses and their related pharmacotherapies, might exacerbate
      the risk of potentially serious adverse events. In this context, the opportunity
      of the more appropriate choice among different fluoroquinolones could be
      applicable.

PMID- 21958024
TI  - PbGEST mediates malaria transmission to both mosquito and vertebrate host.
AB  - The malaria life cycle relies on the successful transfer of the parasite between
      its human and mosquito hosts. We identified a Plasmodium berghei secreted protein
      (PBANKA_131270) that plays distinct roles in both the mammal-to-mosquito and the
      mosquito-to-mammal transitions. This protein, here named gamete egress and
      sporozoite traversal (GEST), plays an important role in the egress of male and
      female gametes from the vertebrate red blood cell. Interestingly, GEST is also
      required following the bite of the infected mosquito, for sporozoite progression
      through the skin. We found PbGEST to be secreted shortly after activation of the
      intraerythrocytic gametocyte, and during sporozoite migration. These findings
      indicate that a single malaria protein may have pleiotropic roles in different
      parasites stages mediating transmission between its insect and mammalian hosts.

PMID- 21958025
TI  - A comparison of fentanyl with tramadol during propofol-based deep sedation for
      pediatric upper endoscopy.
AB  - AIM: This study was conducted to compare the efficacy and safety of tramadol with
      those of fentanyl and to evaluate the impact of age in pediatric patients
      undergoing upper gastrointestinal endoscopy (UGIE). METHODS: Eighty patients with
      ASA I-II, aged 1-16 years, undergoing UGIE were included in this study. Baseline
      anesthesia was maintained with 1 mg.kg(-1) propofol, and then, the patients were
      randomly assigned to receive 2 MUg.kg(-1) fentanyl (group F, n = 40) or 2 mg.kg(
      1) tramadol (group T, n = 40). Additional propofol, 0.5-1 mg.kg(-1), was
      administered when needed. Heart rate, mean arterial pressure, oxygen saturation
      (SpO(2)), and sedation scores were recorded at baseline, induction, and every 5
      min. Endoscopy duration, recovery time, and adverse effects were recorded. The
      data were separated for subgroup analyses based on the age of 0-2, 2-12, and over
      12 years. RESULTS: Fentanyl significantly decreased the saturation at induction,
      5th min and 10th min in patients of 0-2 years; at 5th and 10th min in 2-12 years;
      and at 5th min in >12 years. In all age subgroups, sedation scores at 10th, 15th,
      and 20th min, the overall frequency of adverse effects, and the recovery time
      were significantly lower in group T compared with group F. CONCLUSION: Tramadol
      in pediatric patients undergoing UGIE provided sedation as efficient as fentanyl
      with a better hemodynamic and respiratory stability and provided a superior
      safety and tolerance in younger children.

PMID- 21958026
TI  - Inhibitory effects of combination of lycopene and genistein on 7,12- dimethyl
      benz(a)anthracene-induced breast cancer in rats.
AB  - Breast cancer is one of the most common cancers in women. Carotenoids and soy
      isoflavones have been postulated to have breast cancer preventive effects. We
      investigated the potential preventive effects of lycopene and genistein, alone
      and in combination, on breast cancer development in female Wistar rats treated
      with 7,12-dimethylbenz[a]anthracene (DMBA), a carcinogen known to induce breast
      tumors. Mammary carcinogenesis was initiated by a single, oral gavage of DMBA (80
      mg/kg body weight) at 55 days of animal age. Fifty female Wistar rats were
      divided into 5 experimental groups having 10 animals per group: Group 1 (normal
      control), Group 2 (DMBA control), Group 3 (DMBA + lycopene), Group 4 (DMBA +
      genistein), and Group 5 (DMBA + lycopene and genistein). Rats were fed either
      lycopene (20 mg /kg bw) or genistein (2 mg /kg bw) by oral gavage (3 times per
      week) starting 2 wk prior to DMBA injection. Treatment was continued for 20 wk.
      Rats treated with DMBA developed mammary tumors with 100% tumor incidence during
      the 20-wk study. Inhibition of mammary cancer incidence by lycopene (70%),
      genistein (60%) and their combination (40%) was observed. Tumor weight decreased
      by 48%, 61%, and 67%, and mean tumor volume decreased by 18%, 35%, and 65% with
      lycopene, genistein, and lycopene + genistein, respectively (P < 0.01 for the
      combination). The proportions of adenocarcinoma masses decreased with lycopene
      and genistein combination (P < 0.05). Administration of lycopene and genistein
      combination suppressed breast cancer development and was associated with a
      decrease in MDA, 8-isoprostane, and 8-OhdG levels and with an increase in serum
      lycopene and genistein levels. Animals administered DMBA developed breast cancer,
      which was associated with increased expression of Bcl-2 and decreased expression
      of Bax, caspase 3, and caspase 9 in mammary tissues. Administration of genistein
      and lycopene in combination was more effective in inhibiting DMBA-induced breast
      tumors and modulating the expression of apoptosis associated proteins than the
      administration of each agent alone. Our results suggest that lycopene and
      genistein are potent antioxidants and, when given in combination, offer maximum
      protection against DMBA-induced mammary carcinogenesis.

PMID- 21958028
TI  - Antinuclear antibody status and risk of death in children and adolescents.
AB  - OBJECTIVES: The association between the presence of antinuclear antibodies (ANA)
      and mortality has been rarely reported. The present study explored the value of
      ANA as a predictor of overall survival in children and adolescents. METHODS:
      Patients younger than 20 years who underwent ANA testing in Chang Gung Memorial
      Hospital (CGMH) from 2000 to 2008 were enrolled in this study. Mortality was
      ascertained by using the National Death Registry of Taiwan. Positive ANA titres
      were categorized as low (1:40 to 1:80), medium (1:160 to 1:320), and high (>=
      1:640). RESULTS: A total of 13 345 subjects (6579 males, 6766 females) were
      enrolled during the 9-year study period. The overall prevalence of low, medium,
      and high ANA titres was 20.8% (n = 2774), 6.0% (n = 804), and 2.5% (n = 338),
      respectively. During 45,140 person-years of follow-up, 146 deaths were identified
      and the crude mortality rates were 3.8 and 3.0 per 1000 person-years for subjects
      with positive and negative ANA test results, respectively (p = 0.130). Compared
      with ANA-negative subjects, the adjusted hazard ratio (HR) for all-cause
      mortality among those with a high ANA titre was 5.18 [95% confidence interval
      (CI) 3.13-8.57]. A low-to-medium ANA titre was not associated with increased
      mortality. Among the 18 deaths in individuals with a high ANA titre, 14 were due
      to systemic lupus erythematosus (SLE). In comparison, five out of 34 deaths among
      those with low-to-medium titres of ANA and none of those with negative ANA were
      related to SLE. CONCLUSIONS: Children and adolescents with high ANA titres should
      receive greater attention and monitoring to prevent unfavourable outcomes because
      they have a higher mortality risk than those with negative ANA results.

PMID- 21958027
TI  - Differential roles of TGIF family genes in mammalian reproduction.
AB  - BACKGROUND: TG-interacting factors (TGIFs) belong to a family of TALE-homeodomain
      proteins including TGIF1, TGIF2 and TGIFLX/Y in human. Both TGIF1 and TGIF2 act
      as transcription factors repressing TGF-beta signalling. Human TGIFLX and its
      orthologue, Tex1 in the mouse, are X-linked genes that are only expressed in the
      adult testis. TGIF2 arose from TGIF1 by duplication, whereas TGIFLX arose by
      retrotransposition to the X-chromosome. These genes have not been characterised
      in any non-eutherian mammals. We therefore studied the TGIF family in the tammar
      wallaby (a marsupial mammal) to investigate their roles in reproduction and how
      and when these genes may have evolved their functions and chromosomal locations.
      RESULTS: Both TGIF1 and TGIF2 were present in the tammar genome on autosomes but
      TGIFLX was absent. Tammar TGIF1 shared a similar expression pattern during
      embryogenesis, sexual differentiation and in adult tissues to that of TGIF1 in
      eutherian mammals, suggesting it has been functionally conserved. Tammar TGIF2
      was ubiquitously expressed throughout early development as in the human and
      mouse, but in the adult, it was expressed only in the gonads and spleen, more
      like the expression pattern of human TGIFLX and mouse Tex1. Tammar TGIF2 mRNA was
      specifically detected in round and elongated spermatids. There was no mRNA
      detected in mature spermatozoa. TGIF2 protein was specifically located in the
      cytoplasm of spermatids, and in the residual body and the mid-piece of the mature
      sperm tail. These data suggest that tammar TGIF2 may participate in
      spermiogenesis, like TGIFLX does in eutherians. TGIF2 was detected for the first
      time in the ovary with mRNA produced in the granulosa and theca cells, suggesting
      it may also play a role in folliculogenesis. CONCLUSIONS: The restricted and very
      similar expression of tammar TGIF2 to X-linked paralogues in eutherians suggests
      that the evolution of TGIF1, TGIF2 and TGIFLX in eutherians was accompanied by a
      change from ubiquitous to tissue-specific expression. The distribution and
      localization of TGIF2 in tammar adult gonads suggest that there has been an ultra
      conserved function for the TGIF family in fertility and that TGIF2 already
      functioned in spermatogenesis and potentially folliculogenesis long before its
      retrotransposition to the X-chromosome of eutherian mammals. These results also
      provide further evidence that the eutherian X-chromosome has actively recruited
      sex and reproductive-related genes during mammalian evolution.

PMID- 21958029
TI  - Expression of pluripotency and multipotency factors in human ocular surface
      tissues.
AB  - AIM: Mechanisms that control ocular surface stem cells (SCs) are unclear. Recent
      studies have shown that several adult SCs express pluripotency markers. Our
      objective was to analyze the expression of key molecules of pluripotency in human
      ocular surface tissues as well as in cultivated limbal epithelium. METHODS: Four
      samples of human corneal, limbal and on amniotic membrane cultivated limbal
      epithelium (HLEC-AM), as well as bulbar and fornical conjunctiva were analyzed.
      Human embryonic stem (ES) cells and human umbilical vein endothelial cells served
      as controls. Expression of corneal epithelial differentiation markers (K3, K12,
      Cx43), putative limbal SC markers (ABCG2, p63, K15), and molecules associated
      with pluripotency/multipotency (NANOG, OCT4, SOX2, KLF4, KIT, NESTIN, PAX6,
      NOTCH1) was examined using real-time polymerase chain reaction (PCR) and
      immunohistochemical staining. RESULTS: Limbal epithelium showed a significantly
      (p < 0.05) higher expression of K15, ABCG2, OCT4, SOX2, NESTIN and NOTCH1, but a
      lower expression of K3 than corneal epithelium. Besides a higher expression of
      ABCG2 in fornix, the expression of pluripotency markers was similar in both
      conjunctival regions, although lower than in limbal epithelium. Expression of
      pluripotency factors in ES cells was significantly higher than in ocular surface
      SCs, whereas the expression in limbal epithelium was the closest to ES cells.
      HLEC-AM in comparison to limbal epithelium showed a lower expression of
      differentiation markers, a similar expression of ABCG2 but a significantly lower
      expression of pluripotency factors. CONCLUSION: Human ocular surface epithelial
      cells and especially limbal epithelial cell express genes are important for
      pluripotency and may have preserved some common mechanisms with pluripotent SCs.

PMID- 21958031
TI  - Differences of cations and anions: their hydration, surface adsorption, and
      impact on water dynamics.
AB  - The higher tendency for anions to accumulate at the salt aqueous solution/air
      interface than that of cations has been observed experimentally and
      theoretically, suggesting that the size and polarizability of the ions play
      essential roles in this effect. Here, we investigate the influence of the
      nonsymmetrical positive-vs-negative charge distribution in water molecules to the
      hydration and surface/bulk partition of the solvated positively and negatively
      charged particles by using molecular dynamics simulations with hypothetical ions
      to validate our theoretical models. The results indicate that positive and
      negative charges (called cations and anions, respectively, although they may not
      really exist in experiments) with all other properties identical are hydrated
      differently and that the anions are more likely to populate at the surface. The
      simulation on a combination series of cations and anions in aqueous solution
      shows significant variations on water dynamics, likely due to the specific
      cooperativity between oppositely charged ions.

PMID- 21958030
TI  - Impact of childhood trauma on functionality and quality of life in HIV-infected
      women.
AB  - BACKGROUND: While there are many published studies on HIV and functional
      limitations, there are few in the context of early abuse and its impact on
      functionality and Quality of Life (QoL) in HIV. METHODS: The present study
      focused on HIV in the context of childhood trauma and its impact on functionality
      and Quality of Life (QoL) by evaluating 85 HIV-positive (48 with childhood trauma
      and 37 without) and 52 HIV-negative (21 with childhood trauma and 31 without)
      South African women infected with Clade C HIV. QoL was assessed using the Quality
      of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), the Patient's
      Assessment of Own Functioning Inventory (PAOFI), the Activities of Daily Living
      (ADL) scale and the Sheehan Disability Scale (SDS). Furthermore, participants
      were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D)
      and the Childhood Trauma Questionnaire (CTQ). RESULTS: Subjects had a mean age of
      30.1 years. After controlling for age, level of education and CES-D scores,
      analysis of covariance (ANCOVA) demonstrated significant individual effects of
      HIV status and childhood trauma on self-reported QoL. No significant
      interactional effects were evident. Functional limitation was, however,
      negatively correlated with CD4 lymphocyte count. CONCLUSIONS: In assessing QoL in
      HIV-infected women, we were able to demonstrate the impact of childhood trauma on
      functional limitations in HIV.

PMID- 21958032
TI  - Prehospital factors associated with mortality in injured air medical patients.
AB  - BACKGROUND: Air medical transport provides rapid transport to definitive care.
      Overtriage and the expense and risk of transport may offset survival benefits.
      OBJECTIVE: We assessed the ability of prehospital factors to predict resource
      need for helicopter-transported patients. METHODS: We performed a prospective,
      observational cohort analysis of injured scene patients taken to one of two level
      I trauma centers from October 2009 to September 2010. Variables analyzed included
      patient demographics, diagnoses, and clinical outcomes (in-hospital mortality,
      emergent surgery within 24 hours, blood transfusion within 24 hours, and
      intensive care unit [ICU] admission >=24 hours, as well as a combined outcome of
      all clinical outcomes). Prehospital variables were prospectively obtained from
      air medical providers at the time of transport and included past medical history,
      mechanism of injury, and clinical factors. We compared those variables with and
      without the outcomes of interest via chi(2) analysis and the Kruskal-Wallis test,
      where appropriate. Multivariate logistic regression identified factors associated
      with outcomes of interest with the intent of developing a clinical prediction
      tool. RESULTS: Five hundred fifty-seven patients were transported during the
      study period. The majority of the patients were male (67%) and white (95%) and
      had an injury that occurred in a rural location (58%). Most injuries were blunt
      (97%), and patients had a median Injury Severity Score (ISS) of 9. The overall
      mortality was 4%; 48% of the patients had one of the four outcomes. The most
      common reasons for requesting air transport were motor vehicle collision (MVC)
      with high-risk mechanism (18%), MVC at a speed greater than 20 mph (18%), Glasgow
      Coma Scale score (GCS) less than 14 (15%), and loss of consciousness (LOC)
      greater than 5 minutes (15%). Factors associated with mortality were age greater
      than 44 years, GCS less than 14, systolic blood pressure (SBP) less than 90 mmHg,
      and flail chest. This model had 100% sensitivity and 50% specificity and missed
      no deaths. The combined endpoint of all four outcomes (death, receipt of blood,
      surgery, ICU admission) included intubation by emergency medical services, two or
      more fractures of the humerus/femur, presence of a neurovascular injury, a crush
      injury to the head, failure to localize to pain on examination, GCS less than 14,
      or the presence of a penetrating head injury. This model had a sensitivity of 57%
      (53%-61%) and a specificity of 78% (75%-87%). CONCLUSIONS: Very few prehospital
      criteria were associated with clinically important outcomes in helicopter
      transported patients. Evidence-based guidelines for the most appropriate
      utilization of air medical transport need to be further evaluated and developed
      for injured patients.

PMID- 21958033
TI  - Prey-dependent retention of dimethylsulfoniopropionate (DMSP) by mixotrophic
      dinoflagellates.
AB  - We investigated the retention of dimethylsulfoniopropionate (DMSP) in
      phototrophic dinoflagellates arising from mixotrophy by estimating the cellular
      content of DMSP in Karlodinium veneficum (mixotrophic growth) fed for 7-10 days
      on either DMSP-rich Amphidinium carterae (phototrophic growth only) or DMSP-poor
      Teleaulax sp. (phototrophic growth only). In K. veneficum fed on DMSP-poor prey,
      the cellular content of DMSP remained almost unchanged regardless of the rate of
      feeding, whereas the cellular content of DMSP in cells of K. veneficum fed on
      DMSP-rich prey increased by as much as 21 times the cellular concentration
      derived exclusively from phototrophic growth. In both cases, significant
      fractions (10-32% in the former case and 55-65% in the latter) of the total DMSP
      ingested by K. veneficum were transformed into dimethylsulfide and other
      biochemical compounds. The results may indicate that the DMSP content of prey
      species affects temporal variations in the cellular DMSP content of mixotrophic
      dinoflagellates, and that mixotrophic dinoflagellates produce DMS through grazing
      on DMSP-rich preys. Additional studies should be performed to examine the
      universality of our finding in other mixotrophic dinoflagellates feeding on
      diverse prey species.

PMID- 21958034
TI  - Antibiotic selection by the promiscuous aminoglycoside acetyltransferase-(3)-IIIb
      is thermodynamically achieved through the control of solvent rearrangement.
AB  - The results presented here show the first known observation of opposite signs of
      change in heat capacity (DeltaC(p)) of two structurally similar ligands binding
      to the same protein site. Neomycin and paromomycin are aminoglycoside antibiotics
      that are substrates for the resistance-conferring enzyme, the aminoglycoside
      acetyltransferase-(3)-IIIb (AAC). These antibiotics are identical to one another
      except at the 6' position where neomycin has an amine and paromomycin has a
      hydroxyl. The opposite trends in DeltaC(p) of binding of these two drugs to AAC
      suggest a differential exposure of nonpolar amino acid side chains. Nuclear
      magnetic resonance experiments further demonstrate significantly different
      changes in AAC upon interaction with neomycin and paromomycin. Experiments in
      H(2)O and D(2)O reveal the first observed temperature dependence of solvent and
      vibrational contributions to DeltaC(p). Coenzyme A significantly influences these
      effects. Together, the data suggest that AAC exploits solvent properties to
      facilitate favorable thermodynamic selection of antibiotics.

PMID- 21958040
TI  - Preparation of RSn(I)-Sn(I)R with two unsymmetrically coordinated Sn(I) atoms and
      subsequent gentle activation of P4.
AB  - This article reports the reduction of [{2,6
      iPr(2)C(6)H(3)NC(CH(3))}(2)C(6)H(3)SnCl] (1) with potassium graphite to afford a
      new distannyne [{2,6-iPr(2)C(6)H(3)NC(CH(3))}(2)C(6)H(3)Sn](2) (2) with a Sn-Sn
      bond. The most striking phenomenon of 2 is the presence of two differently
      coordinated Sn atoms (one is three-coordinated, the other is four-coordinated).
      The Sn-Sn bond length in 2 is 2.8981(9) A, which is very close to that of a Sn-Sn
      single bond (2.97-3.06 A). To elucidate the nature of the Sn-Sn bond, DFT
      calculation is carried out that shows there is no multiple bond character in 2.
      Furthermore, the reaction of 2 with white P(4) affords the
      tetraphosphabicylobutane derivative 3. This is the first example of gentle
      activation of white phosphorus by a compound with low valent Sn atoms. Note that,
      unlike 2, in 3 both Sn atoms are four-coordinated.

PMID- 21958041
TI  - Cytochrome c biogenesis System I.
AB  - Cytochromes c are widespread respiratory proteins characterized by the covalent
      attachment of heme. The formation of c-type cytochromes requires, in all but a
      few exceptional cases, the formation of two thioether bonds between the two
      cysteine sulfurs in a -CXXCH- motif in the protein and the vinyl groups of heme.
      The vinyl groups of the heme are not particularly activated and therefore the
      addition reaction does not physiologically occur spontaneously in cells. There
      are several diverse post-translational modification systems for forming these
      bonds. Here, we describe the complex multiprotein cytochrome c maturation (Ccm)
      system (in Escherichia coli comprising the proteins CcmABCDEFGH), also called
      System I, that performs the heme attachment. System I is found in plant
      mitochondria, archaea and many Gram-negative bacteria; the systems found in other
      organisms and organelles are described elsewhere in this minireview series.

PMID- 21958042
TI  - Environmental risk assessment of fluctuating diazinon concentrations in an urban
      and agricultural catchment using toxicokinetic-toxicodynamic modeling.
AB  - Temporally resolved environmental risk assessment of fluctuating concentrations
      of micropollutants is presented. We separated the prediction of toxicity over
      time from the extrapolation from one to many species and from acute to sublethal
      effects. A toxicokinetic-toxicodynamic (TKTD) model predicted toxicity caused by
      fluctuating concentrations of diazinon, measured by time-resolved sampling over
      108 days from three locations in a stream network, representing urban,
      agricultural and mixed land use. We calculated extrapolation factors to quantify
      variation in toxicity among species and effect types based on available toxicity
      data, while correcting for different test durations with the TKTD model. Sampling
      from the distribution of extrapolation factors and prediction of time-resolved
      toxicity with the TKTD model facilitated subsequent calculation of the risk of
      undesired toxic events. Approximately one-fifth of aquatic organisms were at risk
      and fluctuating concentrations were more toxic than their averages. Contribution
      of urban and agricultural sources of diazinon to the overall risk varied. Thus
      using fixed concentrations as water quality criteria appears overly simplistic
      because it ignores the temporal dimension of toxicity. However, the improved
      prediction of toxicity for fluctuating concentrations may be small compared to
      uncertainty due to limited diversity of toxicity data to base the extrapolation
      factors on.

PMID- 21958043
TI  - Zyflamend reduces the expression of androgen receptor in a model of castrate
      resistant prostate cancer.
AB  - Prostate cancer is the most commonly diagnosed solid malignancy, and tumor cells
      eventually transform to castrate resistance through multiple pathways including
      activation of the androgen receptor via insulin-like growth factor receptor (IGF
      1R) signaling involving phospho-AKT (pAKT). In this study, a mixture of herbal
      extracts, Zyflamend(r), was used as a treatment in a model of castrate-resistant
      prostate cancer using CWR22Rv1 cells. Zyflamend reduced androgen receptor and IGF
      1R expression along with a reduction of IGF-1-mediated proliferation of CWR22Rv1
      cells. IGF-1 induced downstream AKT phosphorylation; however, the induction of
      pAKT was not associated with androgen receptor expression. Further,
      constitutively active form of AKT had no effect on nuclear expression of androgen
      receptor, indicating that upregulation of pAKT did not promote androgen receptor
      expression or nuclear translocation in castrate-resistant CWR22Rv1 cells.
      Conversely, Zyflamend reduced androgen receptor expression following IGF-1
      stimulation and in cells overexpressing pAKT. These results demonstrated that
      Zyflamend inhibited IGF-1-stimulated cell growth, IGF-1R expression, and androgen
      receptor expression and its nuclear localization, but these effects were not
      dependent upon phosphatidylinositol 3-kinase/pAKT signaling. In conclusion,
      Zyflamend decreased cell proliferation and inhibited IGF-1R and androgen receptor
      expression in a phosphatidylinositol 3-kinase/pAKT independent manner.

PMID- 21958044
TI  - Pharmacokinetic and pharmacodynamic evaluation of tigecycline.
AB  - INTRODUCTION: As the spread of multidrug-resistant (MDR) and extensive drug
      resistant (XDR) organisms constitutes a real threat for patients, new
      antimicrobials are needed. Tigecycline, the first-in-class glycylcycline,
      possesses an extended spectrum of antimicrobial activity including MDR and XDR
      organisms, which holds promise as a treatment option beyond currently approved
      indications and deserves expanded evaluation of its
      pharmacokinetics/pharmacodynamics (PK/PD). AREAS COVERED: This review highlights
      the areas where our knowledge on PK/PD of tigecycline has been both strengthened
      and questioned during the recent years. New information has become available on
      the PK of tigecycline in patients with complicated skin and skin structure
      infections, complicated intra-abdominal infection, community- and nosocomial
      acquired pneumonia. Human PD data from clinical trials linking tigecycline drug
      exposure to clinical, microbiological and toxicological outcomes are also of
      great interest. EXPERT OPINION: Tigecycline remains one of our last resorts
      against MDR pathogens; its clear role has to be re-defined through intense PK/PD
      applications; dose escalation and exploration of combinations with other
      antibiotics seem to be the first step towards an expansion of its currently
      approved indications. The lung remains the most controversial and challenging
      site regarding the PK/PD standpoint due to the predominance of Acinetobacter
      baumannii and carbapenemase-producing Klebsiella pneumoniae among ventilator
      associated pneumonia infections, for which tigecycline is mostly used off-label.

PMID- 21958045
TI  - Beyond bilateral symmetry: geometric morphometric methods for any type of
      symmetry.
AB  - BACKGROUND: Studies of symmetric structures have made important contributions to
      evolutionary biology, for example, by using fluctuating asymmetry as a measure of
      developmental instability or for investigating the mechanisms of morphological
      integration. Most analyses of symmetry and asymmetry have focused on organisms or
      parts with bilateral symmetry. This is not the only type of symmetry in
      biological shapes, however, because a multitude of other types of symmetry exists
      in plants and animals. For instance, some organisms have two axes of reflection
      symmetry (biradial symmetry; e.g. many algae, corals and flowers) or rotational
      symmetry (e.g. sea urchins and many flowers). So far, there is no general method
      for the shape analysis of these types of symmetry. RESULTS: We generalize the
      morphometric methods currently used for the shape analysis of bilaterally
      symmetric objects so that they can be used for analyzing any type of symmetry.
      Our framework uses a mathematical definition of symmetry based on the theory of
      symmetry groups. This approach can be used to divide shape variation into a
      component of symmetric variation among individuals and one or more components of
      asymmetry. We illustrate this approach with data from a colonial coral that has
      ambiguous symmetry and thus can be analyzed in multiple ways. Our results
      demonstrate that asymmetric variation predominates in this dataset and that its
      amount depends on the type of symmetry considered in the analysis. CONCLUSIONS:
      The framework for analyzing symmetry and asymmetry is suitable for studying
      structures with any type of symmetry in two or three dimensions. Studies of
      complex symmetries are promising for many contexts in evolutionary biology, such
      as fluctuating asymmetry, because these structures can potentially provide more
      information than structures with bilateral symmetry.

PMID- 21958046
TI  - Utilization of different types of dietary fibres by potential probiotics.
AB  - A better understanding of the functionality of probiotics and dietary fibres with
      prebiotic activity is required for the development of improved synbiotic
      preparations. In this study, utilization of beta(2-1) fructans,
      galactooligosaccharides, and plant polysaccharides as prebiotics by lactobacilli,
      bifidobacteria, and pediococci was investigated. Our results demonstrate that
      prebiotics with linear chains consisting of galactose units are better utilized
      by probiotics than are those consisting of glucose and fructose units, and the
      ability of probiotic bacteria to utilize prebiotics is strain-specific. In
      addition, rye fructooligosaccharides represent a prebiotic fibre that supports
      the growth of a wide range of probiotic cultures and as such has a potential to
      improve the successfulness of probiotic treatments. This study also demonstrates
      dietary fibre utilization by pediococci and provides data supporting the possible
      use of pediococci as a probiotic in synbiotic combinations.

PMID- 21958048
TI  - A review of duodenal metastases from squamous cell carcinoma of the cervix
      presenting as an upper gastrointestinal bleed.
AB  - Upper gastrointestinal bleeding due to duodenal metastases is extremely uncommon.
      Extra-pelvic spread of squamous cell carcinoma (SCC) of the cervix to the small
      bowel is rare with only 6 reported cases in the English literature since
      1981(PubMed, Medline).We report the case of a 49-year-old woman who presented
      with upper-gastrointestinal bleeding two years after the diagnosis of SCC of the
      cervix. At esophagogastroduodenoscopy, there was a stricture in the second part
      of the duodenum which was biopsied for a suspected neoplastic lesion. Histologic
      and immunohistochemical examination showed a malignant lesion with
      characteristics identical to her original tumor in the cervix confirming the
      duodenal metastases.The clinical presentation of a 'malignant' upper
      gastrointestinal bleed due to duodenal metastases from SCC of the cervix is
      unusual. Awareness of such infrequent patterns of metastases in cervical cancer
      confirmed by histopathological diagnosis is important for best practice
      therapeutic decisions in these patients.

PMID- 21958049
TI  - Spontaneous remission of idiopathic aldosteronism after long-term treatment with
      spironolactone: results from the German Conn's Registry.
AB  - CONTEXT: Primary aldosteronism (PA) is mainly caused by aldosterone-producing
      adenoma and idiopathic bilateral adrenal hyperplasia (IHA). Recently, spontaneous
      resolution of IHA has been described. OBJECTIVE: We aimed to determine the
      frequency of spontaneous remission of PA during long-term treatment with
      mineralocorticoid receptor (MR) antagonists. DESIGN, SETTING AND PATIENTS: Thirty
      seven patients of the Munich PA registry with IHA treated by MR antagonists were
      investigated. The patients were identified retrospectively by chart review and
      prospectively assessed by clinical and biochemical means. MAIN OUTCOME MEASURES:
      Complete remission of IHA was defined as normal aldosterone to renin ratio (ARR),
      normal suppression test and normalization of hypokalaemia in the presence of
      normal blood pressure. Partial remission was defined as normalization of normal
      ARR, normal suppression test and normalization of hypokalaemia in the presence of
      persistent hypertension. RESULTS: The mean period of MR antagonist treatment was
      5.8 +/- 0.7 years in the patients. We identified two of 37 (5.4%) patients with
      spontaneous remission: one with complete remission and one with partial
      remission. CONCLUSION: Remission of IHA in PA may occur in some patients after
      long-term mineralocorticoid antagonist treatment.

PMID- 21958050
TI  - Simple theoretical model for ion cooperativity in aqueous solutions of simple
      inorganic salts and its effect on water surface tension.
AB  - Careful analysis of experimental data showed that the salt aqueous solution/air
      surface tension depends on a rather complicated manner of salt composition and
      points to the importance of ion cooperativity. In this short article, we include
      the selective binding of anions over cations at interfaces (as revealed from
      molecular dynamics simulations, spectroscopic measurements, and Record's analysis
      of the surface tension data) and the anion-cation association (based on the
      observation of matching water affinity) in a simple theoretical model to
      understand salt effects on surface tension. The introduction of the surface
      effect and ion association provides a qualitative explanation of the experimental
      data, in particular, the strong anion dependence of the cations' rank according
      to their ability of increasing water surface tension. We hope that the physical
      insight provided by this study can be used to point to new directions for more
      detailed studies.

PMID- 21958051
TI  - Aversive effect of tannic acid on drinking behavior in mice of an inbred strain:
      potential animal model for assessing astringency.
AB  - Astringency, an orosensory sensation associated with dietary tannins, contributes
      to food appetitiveness/aversiveness. However, astringency perception varies
      greatly among individuals. This study examined whether genetically homogeneous
      naive mice display appetitiveness/aversiveness when provided with tannin
      containing drink solutions. Ingestion of serial dilutions of tannic acid (TA) by
      inbred mice (A/Snell) was assessed by a one-bottle preference test. Drink intake
      was far predominant at night (circadian rhythm). TA concentration-dependently
      inhibited daily drink consumption. Overnight consumption of TA solutions (range =
      0.5-8 g/L) decreased linearly to zero during the first night and was recovered
      significantly during subsequent nights. TA also inhibited drink consumption in
      another two inbred mouse strains. The protein fraction of saliva collected from
      naive mice was markedly reactive with TA at the concentrations shown to affect
      drink consumption. Thus, testing for drink ingestion in inbred mice during short
      term (overnight) exposure to tannin-containing liquid foods represents an
      advantageous animal model for assessing astringency.

PMID- 21958053
TI  - Asthma and rhinitis by storage mites.

PMID- 21958052
TI  - Matrix metalloproteinases and descending aortic aneurysms: parity, disparity, and
      switch.
AB  - Central to the pathologic changes in developing aortic aneurysms are alterations
      in the abundance and activity of proteases, of which the most important for
      aneurysm production comprise the matrix metalloproteinase (MMP) family. In this
      review, literature demonstrating the role of MMPs in the development of aortic
      aneurysms is presented, with emphasis on the parity and disparity between the
      thoracic and abdominal aorta. Furthermore, the role of embryologic cellular
      origins and evidence of phenotypic switch will be addressed in terms of how this
      process alters MMP production during aneurysm development.

PMID- 21958054
TI  - The relevance of WHO injury surveillance guidelines for evaluation: learning from
      the aboriginal community-centered injury surveillance system (ACCISS) and two
      institution-based systems.
AB  - BACKGROUND: Over the past three decades, the capacity to develop and implement
      injury surveillance systems (ISS) has grown worldwide and is reflected by the
      diversity of data gathering environments in which ISS operate. The capacity to
      evaluate ISS, however, is less advanced and existing evaluation guidelines are
      ambiguous. Furthermore, the applied relevance of these guidelines to evaluate ISS
      operating in various settings is unclear. The aim of this paper was to examine
      how the World Health Organization (WHO) injury surveillance guidelines have been
      applied to evaluate systems operating in three different contexts. METHODS: The
      attributes of a good surveillance system as well as instructions for conducting
      evaluations, outlined in the WHO injury surveillance guidelines, were used to
      develop an analytical framework. Using this framework, a comparative analysis of
      the application of the guidelines was conducted using; the Aboriginal Community
      Centered Injury Surveillance System (ACCISS) from Canada, the Shantou-Emergency
      Department Injury Surveillance Project (S-EDISP) from China, and the Yorkhill
      Canadian Hospitals Injury Reporting and Prevention Program (Y-CHIRPP) imported
      from Canada and implemented in Scotland. RESULTS: The WHO guidelines provide only
      a basic platform for evaluation. The guidelines over emphasize epidemiologic
      attributes and methods and under emphasize public health and injury prevention
      perspectives requiring adaptation for context-based relevance. Evaluation
      elements related to the dissemination and use of knowledge, acceptability, and
      the sustainability of ISS are notably inadequate. From a public health
      perspective, alternative reference points are required for re-conceptualizing
      evaluation paradigms. This paper offers an ISS evaluation template that considers
      how the WHO guidelines could be adapted and applied. CONCLUSIONS: Findings
      suggest that attributes of a good surveillance system, when used as evaluation
      metrics, cannot be weighted equally across ISS. In addition, the attribute of
      acceptability likely holds more relevance than previously recognized and should
      be viewed as a critical underpinning attribute of ISS. Context-oriented
      evaluations sensitive to distinct operational environments are more likely to
      address knowledge gaps related to; understanding links between the production of
      injury data and its use, and the effectiveness, impact, and sustainability of
      ISS. Current frameworks are predisposed to disassociating epidemiologic
      approaches from subjective factors and social processes.

PMID- 21958056
TI  - N-Prolinylanthranilamide pseudopeptides as bifunctional organocatalysts for
      asymmetric aldol reactions.
AB  - Proline anthranilamide-based pseudopeptides were shown to be effective
      organocatalysts for enantioselective direct aldol reactions of a selection of
      aldehydes with various ketones with excellent yield, enantioselectivity up to 99%
      and anti to syn diastereoselectivity up to 25:1.

PMID- 21958057
TI  - Expression of ICOSLG on mouse hematologic neoplasm cell lines and their influence
      on cytotoxicity in allogeneic mixed lymphocyte reactions.
AB  - In this study, we sought to determine whether the expression of inducible co
      stimulator ligand (ICOSLG) on mouse hematologic neoplasm cells influences
      cytotoxicity. Using flow cytometry, we examined the expression of ICOSLG in mouse
      hematologic neoplasm cell lines for the first time and used FBL3/A20 as targets
      to study. Effectors and targets were incubated at effector:target (E:T) ratios
      ranging from 5:1 to 50:1 for 10 h. Enzyme-linked immunosorbent assay was used to
      assess the expression of cytokines associated with type 2 T helper cells. We
      found that FBL3, A20 and P388 cells expressed ICOSLG. At E:T ratios ranging from
      20:1 to 30:1, the cytotoxic activity of alloreactive T cells was significantly
      increased when ICOSLG was blocked (p < 0.05). We also found that ICOSLG blockade
      was associated with decreased expression of interleukin 4 and interleukin 10. Our
      results indicate that ICOSLG blockade may enhance cytotoxity in allogeneic mixed
      lymphocyte-hematologic neoplasm cell reactions.

PMID- 21958059
TI  - Hydrophilic coating of mitotane-loaded lipid nanoparticles: preliminary studies
      for mucosal adhesion.
AB  - The aim of the present work was to load mitotane, an effective drug for
      adrenocortical carcinoma treatment, in solid lipid nanoparticles (SLN) and
      nanostructured lipid carriers (NLC). The SLN and NLC were successfully prepared
      by high shear homogenization followed by hot high pressure homogenization.
      Formulations were composed of cetyl palmitate as the solid lipid for SLN, whereas
      for NLC PEGylated stearic acid was selected as solid lipid and medium chain
      triacylglycerols as the liquid lipid. Tween(r) 80 and Span(r) 85 were used as
      surfactants for all formulations. The particle size, zeta potential,
      polydispersity index (PI), encapsulation efficiency (EE), and loading capacity
      (LC) were evaluated. The SLN showed a mean particle size of 150 nm, PI of 0.20,
      and surface charge -10 mV, and the EE and LC could reach up to 92.26% and 0.92%,
      respectively. The NLC were obtained with a mean particle size of 250 nm, PI of
      0.30, zeta potential -15 mV and 84.50% EE, and 0.84% LC, respectively.
      Hydrophilic coating of SLN with chitosan or benzalkonium chloride was effective
      in changing zeta potential from negative to positive values. The results suggest
      that mitotane was efficiently loaded in SLN and in NLC, being potential delivery
      systems for improving mitotane LC and controlled drug release.

PMID- 21958058
TI  - Oxygen reactivity in flavoenzymes: context matters.
AB  - Many flavoenzymes--oxidases and monooxygenases--react faster with oxygen than
      free flavins do. There are many ideas on how enzymes cause this. Recent work has
      focused on the importance of a positive charge near N5 of the reduced flavin.
      Fructosamine oxidase has a lysine near N5 of its flavin. We measured a rate
      constant of 1.6 * 10(5) M(-1) s(-1) for its reaction with oxygen. The Lys276Met
      mutant reacted with a rate constant of 291 M(-1) s(-1), suggesting an important
      role for this lysine in oxygen activation. The dihydroorotate dehydrogenases from
      E. coli and L. lactis also have a lysine near N5 of the flavin. They react with
      O(2) with rate constants of 6.2 * 10(4) and 3.0 * 10(3) M(-1) s(-1),
      respectively. The Lys66Met and Lys43Met mutant enzymes react with rate constants
      that are nearly the same as those for the wild-type enzymes, demonstrating that
      simply placing a positive charge near N5 of the flavin does not guarantee
      increased oxygen reactivity. Our results show that the lysine near N5 does not
      exert an effect without an appropriate context; evolution did not find only one
      mechanism for activating the reaction of flavins with O(2).

PMID- 21958060
TI  - Substantial postoperative pain is common among children undergoing laparoscopic
      appendectomy.
AB  - BACKGROUND: Laparoscopic appendectomy is one of the most common surgical
      procedures performed in children. However, to our knowledge, the postoperative
      pain experience of children undergoing laparoscopic appendectomy has never been
      described. In this study, we assessed the postoperative pain experience of
      children undergoing laparoscopic appendectomy. METHODS: A retrospective chart
      review of children aged 9-17 years undergoing laparoscopic appendectomy at a
      large academic medical center from 2004 to 2010 was performed. Demographic and
      clinical characteristics and self-reported pain scores (0-10 numeric rating
      scale) during hospitalization were abstracted from the medical record. Pain
      scores >=4 were classified as moderate or severe. If >=60% of pain ratings were
      moderate or severe during a specified time period (e.g., particular postoperative
      day), then the child was defined as experiencing substantial pain during that
      time. Pain outcomes were summarized using descriptive statistics. Secondary
      analyses assessed the predictors of substantial postoperative pain. RESULTS:
      Hundred and eighty-six children underwent laparoscopic appendectomy during the
      study period. One in three children experienced substantial postoperative pain on
      the day of surgery, and one in five children continued to have substantial pain
      the next day. Commonly available clinical and demographic characteristics were
      poor predictors of substantial postoperative pain. CONCLUSION: These preliminary
      data suggest that substantial postoperative pain is common in children undergoing
      laparoscopic appendectomy. More studies of postoperative pain outcomes among
      children undergoing laparoscopic appendectomy and other common pediatric surgical
      procedures are needed.

PMID- 21958061
TI  - Protein separation by electrophoretic-electroosmotic focusing on supported lipid
      bilayers.
AB  - An electrophoretic-electroosmotic focusing (EEF) method was developed and used to
      separate membrane-bound proteins and charged lipids based on their charge-to-size
      ratio from an initially homogeneous mixture. EEF uses opposing electrophoretic
      and electroosmotic forces to focus and separate proteins and lipids into narrow
      bands on supported lipid bilayers (SLBs). Membrane-associated species were
      focused into specific positions within the SLB in a highly repeatable fashion.
      The steady-state focusing positions of the proteins could be predicted and
      controlled by tuning experimental conditions, such as buffer pH, ionic strength,
      electric field, and temperature. Careful tuning of the variables should enable
      one to separate mixtures of membrane proteins with only subtle differences. The
      EEF technique was found to be an effective way to separate protein mixtures with
      low initial concentrations, and it overcame diffusive peak broadening to allow
      four bands to be separated simultaneously within a 380 MUm wide isolated
      supported membrane patch.

PMID- 21958062
TI  - s-Block organometallics: analysis of ion-association and noncovalent interactions
      on structure and function in benzyl-based compounds.
AB  - The organometallic chemistry of alkali and alkaline-earth metals has been marred
      by synthetic setbacks because of their high reactivity. Advances in their
      synthesis and a better understanding of the stabilization effects of ligands and
      coligands have resulted in the revolution of s-block organometallics. Among
      those, benzyl-based derivatives have played a key role in developing this
      chemistry because factors such as the ligand size, charge delocalization, and
      introduction of electronic parameters along with metal effects can be analyzed.
      This article will focus on s-block benzylates and di- and triphenylmethanide
      derivatives with specific emphasis on the factors that stabilize the highly
      reactive metal species.

PMID- 21958067
TI  - China's functioning market for sulfur dioxide scrubbing technologies.
AB  - Countries' differing positions in technology transfer have been a barrier in
      climate negotiations. Developed countries want market-based solutions with
      effective protection of intellectual property rights, whereas developing
      countries look for external support and nonmarket solutions. Although China has
      shared common negotiation positions with other developing countries, it has
      actually relied heavily on markets to acquire foreign technologies. This paper
      systematically examines the case of sulfur dioxide (SO(2)) scrubbing
      technologies, with first-hand information from the author's field interviews, to
      explain why such a functioning market for technology could emerge in China.
      Existing studies focus mainly on technology suppliers or licensors and this paper
      adds to the understanding of consumers or licensees. Two factors should have made
      major contributions to the market's emergence: (i) the huge size of the Chinese
      market of SO(2) scrubbers, and (ii) the knowhow and maturity of the technologies.
      Market-based solutions of technology transfer might help large developing
      countries like China and India to efficiently acquire mature environmental
      technologies and satisfy their rapid development.

PMID- 21958066
TI  - Activation and inhibition of pyruvate carboxylase from Rhizobium etli.
AB  - While crystallographic structures of the R. etli pyruvate carboxylase (PC)
      holoenzyme revealed the location and probable positioning of the essential
      activator, Mg(2+), and nonessential activator, acetyl-CoA, an understanding of
      how they affect catalysis remains unclear. The current steady-state kinetic
      investigation indicates that both acetyl-CoA and Mg(2+) assist in coupling the
      MgATP-dependent carboxylation of biotin in the biotin carboxylase (BC) domain
      with pyruvate carboxylation in the carboxyl transferase (CT) domain. Initial
      velocity plots of free Mg(2+) vs pyruvate were nonlinear at low concentrations of
      Mg(2+) and a nearly complete loss of coupling between the BC and CT domain
      reactions was observed in the absence of acetyl-CoA. Increasing concentrations of
      free Mg(2+) also resulted in a decrease in the K(a) for acetyl-CoA. Acetyl
      phosphate was determined to be a suitable phosphoryl donor for the catalytic
      phosphorylation of MgADP, while phosphonoacetate inhibited both the
      phosphorylation of MgADP by carbamoyl phosphate (K(i) = 0.026 mM) and pyruvate
      carboxylation (K(i) = 2.5 mM). In conjunction with crystal structures of T882A R.
      etli PC mutant cocrystallized with phosphonoacetate and MgADP, computational
      docking studies suggest that phosphonoacetate could coordinate to one of two
      Mg(2+) metal centers in the BC domain active site. Based on the pH profiles,
      inhibition studies, and initial velocity patterns, possible mechanisms for the
      activation, regulation, and coordination of catalysis between the two spatially
      distinct active sites in pyruvate carboxylase from R. etli by acetyl-CoA and
      Mg(2+) are described.

PMID- 21958068
TI  - Effect of telmisartan addition to amlodipine on ankle edema development in
      treating hypertensive patients.
AB  - OBJECTIVE: The objective of this research was to evaluate the effect of
      telmisartan addition to amlodipine, on peripheral edema in hypertensive patients.
      RESEARCH DESIGN AND METHODS: Seventy-five outpatients were randomized to
      amlodipine (A) 10 mg or telmisartan (T) 80 mg, or amlodipine 10 mg plus
      telmisartan 80 mg, for 6 weeks, in three crossover periods. MAIN OUTCOME
      MEASURES: Blood pressure, ankle foot volume (AFV) and pretibial subcutaneous
      tissue pressure (PSTP) were evaluated, as were plasma norepinephrine and plasma
      active renin (PAR). RESULTS: Amlodipine-telmisartan combination induced greater
      SBP/DBP reduction (-28.1/21.7 mmHg, p < 0.0001 vs baseline) compared with
      monotherapy with both amlodipine and telmisartan. Amlodipine monotherapy
      increased AFV by 26.7%, and PSTP by 83.2% (both p < 0.01). Adding telmisartan to
      amlodipine produced a significantly lesser increase in both AFV (+7.9%, p < 0.01
      vs amlodipine) and PSTP (+23.8%, p < 0.01 vs amlodipine). Plasma norepinephrine
      levels were increased by amlodipine (+134.3 pg/ml, p < 0.01); such an increase
      was attenuated by the addition of telmisartan (+55 pg/ml, p < 0.05 vs
      amlodipine). PAR was slightly increased by amlodipine (+21.5 pg/ml, p < 0.05) and
      more by telmisartan alone (+62.5 pg/ml) and telmisartan-amlodipine combination
      (+71.3 pg/ml; both p < 0.01). CONCLUSIONS: The addition of telmisartan to
      amlodipine significantly attenuated amlodipine-induced edema formation. The
      reduction of amlodipine-induced reflex-sympathetic activation by telmisartan
      might have contributed to such an effect.

PMID- 21958069
TI  - Male gender preference, female gender disadvantage as risk factors for
      psychological morbidity in Pakistani women of childbearing age - a life course
      perspective.
AB  - BACKGROUND: In Pakistan, preference for boys over girls is deeply culturally
      embedded. From birth, many women experience gendered disadvantages; less access
      to scarce resources, poorer health care, higher child mortality, limited
      education, less employment outside of the home and circumscribed autonomy. The
      prevalence of psychological morbidity is exceptionally high among women. We
      hypothesise that, among women of childbearing age, gender disadvantage is an
      independent risk factor for psychological morbidity METHODS: A cross-sectional
      catchment area survey of 525 women aged 18 to 35 years living in Islamabad and
      Rawalpindi. The effect of gender disadvantage was assessed as a latent variable
      using structural equation modelling. Indicators were parental gender preference,
      low parental care, parental overprotection, limited education, early age at
      marriage, marital dissatisfaction and low autonomy. Psychological morbidity was
      assessed using the 20 item Self Reporting Questionnaire (SRQ). RESULTS: Gender
      disadvantage was independently predictive of psychological morbidity. Among
      married women, socio-economic status did not predict psychological morbidity, and
      the effect of education was mediated through gender disadvantage rather than
      socioeconomic status (SES). The women's own preference for a male child was
      strongly predicted by their perceptions of having been disadvantaged by their
      gender in their families of origin. CONCLUSIONS: The high prevalence of
      psychological morbidity among women in Pakistan is concerning given recently
      reported strong associations with low birth weight and infant stunting. Social
      action, public policies and legislation are indicated to reduce culturally
      embedded preferences. Neglect of these fundamentals will entrench consequent
      inequities including gender bias in access to education, a key millennium
      development goal.

PMID- 21958070
TI  - Effects of phosphatidylethanolamine N-methyltransferase on phospholipid
      composition, microvillus formation and bile salt resistance in LLC-PK1 cells.
AB  - Bile salts are potent detergents and can disrupt cellular membranes, which causes
      cholestasis and hepatocellular injury. However, the mechanism for the resistance
      of the canalicular membrane against bile salts is not clear.
      Phosphatidylethanolamine (PE) is converted to phosphatidylcholine (PC) in the
      liver by phosphatidylethanolamine N-methyltransferase (PEMT). In this study, to
      investigate the effect of PEMT expression on the resistance to bile salts, we
      established an LLC-PK1 cell line stably expressing PEMT. By using enzymatic
      assays, we showed that the expression of PEMT increased the cellular PC content,
      lowered the PE content, but had no effect on the sphingomyelin content.
      Consequently, PEMT expression led to reductions in PE/PC and sphingomyelin/PC
      ratios. Mass spectrometry demonstrated that PEMT expression increased the levels
      of PC species containing longer acyl chains and almost all ether-linked PC
      species. PEMT expression enhanced the resistance to duramycin and lysenin,
      suggesting decreased ratios of PE and sphingomyelin in the apical membrane,
      respectively. In addition, SEM revealed that PEMT expression increased the
      diameter of microvilli. The expression of PEMT resulted in reduced resistance to
      unconjugated bile salts, but surprisingly in increased resistance to conjugated
      bile salts, which might be attributable to modifications of the phospholipid
      composition and/or structure in the apical membrane. Because most bile salts
      exist as conjugated forms in the bile canaliculi, PEMT may be important in the
      protection of hepatocytes from bile salts and in cholestatic liver injury.

PMID- 21958071
TI  - Detection of growth-related QTL in turbot (Scophthalmus maximus).
AB  - BACKGROUND: The turbot (Scophthalmus maximus) is a highly appreciated European
      aquaculture species. Growth related traits constitute the main goal of the
      ongoing genetic breeding programs of this species. The recent construction of a
      consensus linkage map in this species has allowed the selection of a panel of 100
      homogeneously distributed markers covering the 26 linkage groups (LG) suitable
      for QTL search. In this study we addressed the detection of QTL with effect on
      body weight, length and Fulton's condition factor. RESULTS: Eight families from
      two genetic breeding programs comprising 814 individuals were used to search for
      growth related QTL using the panel of microsatellites available for QTL
      screening. Two different approaches, maximum likelihood and regression interval
      mapping, were used in order to search for QTL. Up to eleven significant QTL were
      detected with both methods in at least one family: four for weight on LGs 5, 14,
      15 and 16; five for length on LGs 5, 6, 12, 14 and 15; and two for Fulton's
      condition factor on LGs 3 and 16. In these LGs an association analysis was
      performed to ascertain the microsatellite marker with the highest apparent effect
      on the trait, in order to test the possibility of using them for marker assisted
      selection. CONCLUSIONS: The use of regression interval mapping and maximum
      likelihood methods for QTL detection provided consistent results in many cases,
      although the high variation observed for traits mean among families made it
      difficult to evaluate QTL effects. Finer mapping of detected QTL, looking for
      tightly linked markers to the causative mutation, and comparative genomics are
      suggested to deepen in the analysis of QTL in turbot so they can be applied in
      marker assisted selection programs.

PMID- 21958072
TI  - Protein side-chain translocation mutagenesis via incorporation of peptoid
      residues.
AB  - For the last few decades, chemistry has played an important role in protein
      engineering by providing a variety of synthetic tools such as chemoselective side
      chain modifications, chemical conjugation, incorporation of non-natural amino
      acids, and the development of protein-mimetic heteropolymers. Here we study
      protein backbone engineering in order to better understand the molecular
      mechanism of protein function and to introduce protease stable, non-natural
      residues into a protein structure. Using a combination of genetic engineering and
      chemical synthesis, we were able to introduce peptoid residues (N-substituted
      glycine residues) at defined positions into bovine pancreatic ribonuclease A.
      This results in a side-chain translocation from the Calpha carbon to the
      neighboring backbone nitrogen atom. To generate these peptoid substitutions, we
      removed the N-terminal S-peptide of the protein by proteolysis and chemically
      conjugated synthetic peptide-peptoid hybrids to the new N-terminus. A triple
      peptoid mutant containing a catalytic His12 peptoid mutation was active with a
      k(cat)/K(m) value of 1.0 * 10(4) M(-1) s(-1). This k(cat)/K(m) value is only 10
      fold lower than the control wild-type conjugate and comparable in magnitude to
      many other natural enzymes. The peptoid mutations increased the chain flexibility
      at the site of peptoid substitution and at its C-terminal neighboring residue.
      Our ability to translocate side chains by one atom along the proten backbone
      advances a synthetic mutagenesis tool and opens up a new level of protein
      engineering.

PMID- 21958073
TI  - Effect of PEG end-group hydrophobicity on lysozyme interactions in solution
      characterized by light scattering.
AB  - We compare protein-protein and protein-polymer osmotic virial coefficients
      measured by static light scattering for aqueous solutions of lysozyme with low
      molecular-weight, hydroxy-terminated (hPEG) and methyl-terminated (mPEG)
      poly(ethylene glycol) at two solution conditions: pH 7.0 and 0.01 M ionic
      strength, and pH 6.2 and 0.8 M ionic strength. We find that adding PEG to aqueous
      lysozyme solutions makes a net repulsive contribution to lysozyme-lysozyme
      interactions, independent of ionic strength and PEG end-group hydrophobicity. PEG
      end-group hydrophobicity has a profound effect on the magnitude of this
      contribution, however, at low ionic strength where mPEG-lysozyme attractive
      interactions become significant. The enhanced attractions promote mPEG-lysozyme
      preferential interactions at the expense of lysozyme self-interactions, which
      leads to lysozyme-lysozyme interactions that are more repulsive in the presence
      of mPEG. These preferential interactions also lead to the preferential exclusion
      of diffusable ions locally around the protein, which results in a pronounced
      ionic strength dependence of mPEG-mediated lysozyme-lysozyme interactions.

PMID- 21958074
TI  - Proteomic analysis of four Brazilian MON810 maize varieties and their four non
      genetically-modified isogenic varieties.
AB  - Profiling techniques have been suggested as a nontargeted approach to detect
      unintended effects in genetically modified (GM) plants. Seedlings from eight
      Brazilian maize varieties, four MON810 GM varieties and four non-GM isogenic
      varieties, were grown under controlled environmental conditions. Physiological
      parameters (aerial part weight, main leaf length, and chlorophyll and total
      protein contents) were compared, and some differences were observed.
      Nevertheless, these differences were not constant among all GM and non-GM
      counterparts. Leaf proteomic profiles were analyzed using two-dimensional gel
      electrophoresis (2DE) coupled to mass spectrometry, using six 2DE gels per
      variety. The comparison between MON810 and its counterpart was limited to
      qualitative differences of fully reproducible protein spot patterns. Twelve
      exclusive proteins were observed in two of four maize variety pairs; all of these
      leaf proteins were variety specific. In this study, MON810 leaf proteomes of four
      varieties were similar to non-GM counterpart leaf proteomes.

PMID- 21958075
TI  - Engineering artificial signaling centers to polarize embryoid body
      differentiation.
AB  - Embryonic stem (ES) cells differentiating as aggregates self-organize dependent
      on Wnt signaling that is initially localized to discrete sites in the aggregate.
      As differentiation proceeds, Wnt signaling expands to most of the aggregates,
      thus resulting in widespread differentiation of mesendodermal progenitors. This
      process resembles primitive streak formation, but the lack of organized
      positional information makes the differentiating aggregates develop in a
      disorganized fashion. Here, we report that exogenous, cellular signaling sources
      can control the site where differentiation initiates in ES cell aggregates.
      Fibroblasts engineered to express cadherins are assembled with ES cells to form
      composite aggregates where the fibroblasts are positioned as a discrete pole.
      When engineered to express secreted Wnt agonists or antagonists, this pole
      functions to localize signaling in a way that polarizes the differentiating
      aggregates. The use of cell adhesion molecules to control morphology of
      developing stem cell aggregates should be widely applicable in tissue
      engineering.

PMID- 21958076
TI  - FCER2 T2206C variant associated with chronic symptoms and exacerbations in
      steroid-treated asthmatic children.
AB  - BACKGROUND: The T2206C FCER2 variant was found previously to be associated with
      IgE levels, exacerbation rates and decreased FCER2 expression in children on
      inhaled corticosteroids (ICS) participating in a clinical trial. This finding has
      not been replicated. We sought to replicate the association between the FCER2
      gene and exacerbations in children with asthma. In addition, we tested the
      hypothesis that the T2206C variant may be associated with other markers of
      steroid resistance such as asthma symptom scores and asthma medication use.
      METHODS: The influence of the T2206C variant on asthma exacerbations (emergency
      department visits or hospitalization), symptoms scores and medication use was
      explored using data from two populations of asthmatic children using ICS:
      Pharmacogenetics of Asthma medication in Children: Medication with ANti
      inflammatory effects study (n = 386) and BREATHE study (n = 939). RESULTS: The
      T2206C variant was associated with increased risk of asthma-related hospital
      visits in both cohorts (OR: 1.91, 95% CI: 1.08-3.40), and meta-analysis with
      previously published results was highly significant (OR: 2.38, 95% CI: 1.47-3.85,
      P = 0.0004). The FCER2 variant was also associated with increased risk of
      uncontrolled asthma measured by Asthma Control Questionnaire (OR: 2.64, 95% CI:
      1.00-6.98) and was associated with increased daily steroid dose (OR: 2.46, 95%
      CI: 1.38-4.39). CONCLUSION: The association between the FCER2 T2206C variant and
      asthma-related hospitalizations in steroid-treated asthma appears robust and may
      also be associated with other indicators of lack of ICS efficacy such as asthma
      symptoms and a requirement for higher daily doses of ICS. Our results suggest
      that the FCER2 T2206C variant might be a useful pharmacogenetic predictor of
      steroid refractory patients.

PMID- 21958077
TI  - Early lesion formation in colorectal carcinogenesis is associated with
      adiponectin status whereas neoplastic lesions are associated with diet and sex in
      C57BL/6J mice.
AB  - Adiponectin is an antiinflammatory and insulin-sensitizing hormone that is
      decreased in obesity. Although controversial, it has been suggested that
      decreased adiponectin contributes to colorectal cancer risk in obesity. To
      further investigate the role of adiponectin in obesity-linked colorectal
      carcinogenesis, we used male and female adiponectin knockout (KO) and wild-type
      (Wt) C57BL/6J mice. Tumorigenesis was induced in all mice with the combined
      treatment of azoxymethane (AOM) and dextran sodium sulfate (DSS). Following
      AOM/DSS treatment, mice were fed a low-fat control (LFC), or high-fat lard (HFL)
      diet for 7 1/2 wk. KO mice developed fewer total lesions than Wt mice, males
      developed fewer lesions than females, and mice fed the HFL diet developed fewer
      lesions than those fed the LFC diet. Early lesion multiplicity was influenced by
      genotype, whereas advanced lesion development was influenced by sex and diet.
      Moreover, lesion types were differentially correlated with serum adipokines and
      colon gene expression of adiponectin receptors, insulin receptor, and toll-like
      receptor 4. These data suggest that in the AOM/DSS model of carcinogenesis,
      adiponectin functions to promote early lesion development whereas sex and diet
      are important regulators of advanced lesion development through pathways involved
      in inflammation and insulin signaling.

PMID- 21958078
TI  - Simultaneous bridge-localized and mixed-valence character in diruthenium radical
      cations featuring diethynylaromatic bridging ligands.
AB  - A series of bimetallic ruthenium complexes [{Ru(dppe)Cp*}(2)(MU-C=CArC=C)]
      featuring diethynylaromatic bridging ligands (Ar = 1,4-phenylene, 1,4
      naphthylene, 9,10-anthrylene) have been prepared and some representative
      molecular structures determined. A combination of UV-vis-NIR and IR
      spectroelectrochemical methods and density functional theory (DFT) have been used
      to demonstrate that one-electron oxidation of compounds [{Ru(dppe)Cp*}(2)(MU
      C=CArC=C)](HC=CArC=CH = 1,4-diethynylbenzene; 1,4-diethynyl-2,5-dimethoxybenzene;
      1,4-diethynylnaphthalene; 9,10-diethynylanthracene) yields solutions containing
      radical cations that exhibit characteristics of both oxidation of the
      diethynylaromatic portion of the bridge, and a mixed-valence state. The
      simultaneous population of bridge-oxidized and mixed-valence states is likely
      related to a number of factors, including orientation of the plane of the
      aromatic portion of the bridging ligand with respect to the metal d-orbitals of
      appropriate pi-symmetry.

PMID- 21958080
TI  - Evaluation of the new AJCC staging system for resectable hepatocellular
      carcinoma.
AB  - BACKGROUND: The aim of this study was to assess the validity of the 7th edition
      of the American Joint Committee on Cancer (AJCC) TNM system (TNM-7) for patients
      undergoing hepatectomy for hepatocellular carcinoma (HCC). METHODS: Partial
      hepatectomies performed for 879 patients from 1993 to 2005 were retrospectively
      reviewed. Clinicopathological factors, surgical outcome, overall survival (OS),
      and disease-free survival (DFS) were analyzed to evaluate the predictive value of
      the TNM-7 staging system. RESULTS: According to the TNM-7 system, differences in
      five-year survival between stages I, II, and III were statistically significant.
      Subgroup analysis of stage III patients revealed that the difference between
      stages II and IIIA was not significant (OS, p = 0.246; DFS, p = 0.105). Further
      stratification of stages IIIA, IIIB and IIIC also did not reveal significant
      differences. Cox proportional hazard models of stage III analyses identified
      additional clinicopathological factors affecting patient survival: lack of tumor
      encapsulation, aspartate aminotransferase (AST) values > 68 U/L, and blood loss >
      500 mL affected DFS whereas lack of tumor encapsulation, AST values > 68 U/L,
      blood loss > 500 mL, and serum alpha-fetoprotein (AFP) values > 200 ng/mL were
      independent factors impairing OS. Stage III factors including tumor thrombus,
      satellite lesions, and tumor rupture did not appear to influence survival in the
      stage III subgroup. CONCLUSIONS: In terms of 5-year survival rates, the TNM-7
      system is capable of stratifying post-hepatectomy HCC patients into stages I, II,
      and III but is unable to stratify stage III patients into stages IIIA, IIIB and
      IIIC. Lack of tumor encapsulation, AST values > 68 U/L, blood loss > 500 mL, and
      AFP values > 200 ng/mL are independent prognostic factors affecting long-term
      survival.

PMID- 21958081
TI  - The association of specific metabolites of lipid metabolism with markers of
      oxidative stress, inflammation and arterial stiffness in men with newly diagnosed
      type 2 diabetes.
AB  - OBJECTIVE: To determine whether circulating metabolic intermediates are
      associated with inflammation, oxidative stress and arterial stiffness in men with
      newly diagnosed type 2 diabetes and investigate the circulating metabolic
      intermediates that may predict the risk of developing diabetes. RESEARCH DESIGN
      AND METHODS: Men with newly diagnosed type 2 diabetes (n = 26) and age- and body
      mass index-matched nondiabetic men (n = 27) were included. We measured
      inflammatory and oxidative markers and arterial stiffness by brachial-ankle pulse
      wave velocity (ba-PWV). Metabolomic profiling was analysed with ultra performance
      liquid chromatography and quadrupole time-of-flight mass spectrometry. RESULTS:
      Diabetic men showed higher circulating levels of glucose, triglyceride, oxidized
      low-density lipoprotein (LDL), high-sensitivity C-reactive protein, interleukin
      (IL)-6, tumour necrosis factor-alpha (TNF-alpha), homeostasis model assessment
      insulin resistance, urinary 8-epi-prostaglandin F(2alpha) (8-epi-PGF(2alpha)) and
      ba-PWV than nondiabetic men. In plasma, 19 metabolites including three amino
      acids, eight acylcarnitines, six lysophosphatidylcholines (lysoPCs), and two
      lysophosphatidylethanolamines (lysoPEs; C18:2 and C22:6) significantly increased
      in diabetes men, whereas serine and lysoPE (C18:1) decreased. Decanoyl carnitine,
      lysoPCs (C14:0, C16:1, C18:1 and C22:6) and lysoPE (C18:1) with variable
      importance in the projection values >1.0 were major plasma metabolites that
      distinguished nondiabetic and diabetic men. Decanoyl carnitine positively
      correlated with oxidized LDL, 8-epi-PGF(2alpha), IL-6, TNF-alpha and ba-PWV. ba
      PWV correlated positively with lysoPCs C14:0 and C16:1, and negatively with
      lysoPE C18:1. 8-epi-PGF(2alpha) correlated positively with lipoprotein-associated
      phospholipase A(2), ba-PWV and lysoPCs (C14:0 and C16:1). The receiver operating
      characteristic curve estimation suggested that decanoyl carnitine and lysoPC
      (C14:0) are the best metabolites for predicting the risk of developing diabetes.
      CONCLUSIONS: Circulating lipid-related intermediate metabolites can be closely
      associated with inflammation, oxidative stress and arterial stiffness in early
      diabetes.

PMID- 21958082
TI  - Implications of worse renal dysfunction and medical comorbidities in patients
      with NASH undergoing liver transplant evaluation: impact on MELD and more.
AB  - Increasing numbers of patients with non-alcoholic steatohepatitis (NASH) are
      referred for liver transplant (LT). Our objective was to characterize patients
      with NASH among referred LT candidates (from 1998 to 2008), and we compared
      demographics, etiology of liver disease, diabetes, hypertension, smoking,
      obesity, cardiac disease, cancer, laboratory data, model for end-stage liver
      disease (MELD), and outcomes between NASH and non-NASH patients. Patients with
      NASH (n = 71) were compared to other chronic liver disease (n = 472). Patients
      with NASH were older (58.7 vs. 52.5 yr, p < 0.0001), Asian (53.5% vs. 34.7%, p =
      0.03) and women (50.7% vs. 32.1%, p = 0.003). Patients with NASH had more
      diabetes, hypertension, obesity, cardiac disease, and smoking history (p < 0.05).
      Patients with NASH were equally likely to have liver cancer, but more likely to
      have non-liver cancers (20.8% vs. 4.4%, p = 0.008). There was no difference in
      MELD, but patients with NASH had lower protime/international normalized ratio
      (1.14 vs. 1.27, p = 0.04) and higher creatinine (1.26 vs. 0.98 mg/dL, p =
      0.0018). Patients with NASH were equally likely to undergo evaluation, listing,
      and transplantation compared to non-NASH patients. While all patients with
      chronic liver disease can have renal dysfunction because of hepatorenal syndrome,
      patients with NASH have more renal dysfunction, perhaps related to diabetes,
      hypertension, and cardiovascular disease. Transplant centers should consider this
      carefully in selection of candidates for LT.

PMID- 21958083
TI  - Maintenance rituximab in follicular non-Hodgkin lymphoma: facts and
      controversies.
AB  - The advent of rituximab, a chimeric monoclonal antibody against CD20, has
      arguably improved and changed the natural history of non-Hodgkin lymphoma and has
      become an essential component of front-line and relapsed disease treatment
      strategies. Given its tolerability and long half-life, rituximab has been
      investigated in the maintenance setting in follicular lymphoma. Several landmark
      studies have demonstrated improvement in progression-free survival in patients
      receiving maintenance rituximab compared to those observed. These favorable
      results were witnessed in front-line and in the relapsed setting using a variety
      of induction programs such as rituximab monotherapy or chemoimmunotherapy.
      Importantly, toxicities were predictable and manageable. Despite these
      encouraging results, many vital and practical questions remain unanswered. In
      this review, we critically analyze the data that led to the widespread use of
      maintenance rituximab in follicular lymphoma and attempt to answer the most
      important questions facing practicing oncologists when deciding on using this
      approach in their patients.

PMID- 21958084
TI  - In vitro characterization and growth inhibition effect of nanostructured lipid
      carriers for controlled delivery of methotrexate.
AB  - The present study describes the design and characterization of nanostructured
      lipid carriers (NLCs) for controlled delivery of methotrexate (MTX). A series of
      NLCs with or without MTX were prepared using different ratios of liquid-lipid to
      solid-lipid and type and concentration of surfactants. The effect of different
      formulation parameters on the physical properties of NLCs, entrapment efficiency
      of MTX and in vitro drug release was evaluated. In addition, the in vitro
      delivery and cytotoxicity of MTX-loaded NLCs against human prostate cancer DU-145
      cells and ovarian human cancer A2780 cells were investigated. Drug loading
      capacity, particle size and surface charge of the prepared NLCs and the in vitro
      MTX release were affected by the formulation parameters. In vitro growth
      inhibition assay using DU-145 and A2780 cancer cell lines showed that drug-free
      NLCs maintained cell viability while MTX-loaded NLCs inhibited the growth of both
      cell lines. In addition, MTX-loaded NLCs showed superior inhibitory effect on
      cell growth over the free drug especially in A2780 cell lines and a higher
      cytotoxic effect on DU-145 at higher drug concentration. The results of the
      current study warrant further exploration for the use NLCs as a controlled
      delivery system for chemotherapeutic agents. 

PMID- 21958086
TI  - Organic dyes incorporating the benzo[1,2-b:4,5-b']dithiophene moiety for
      efficient dye-sensitized solar cells.
AB  - A new class of organic sensitizers incorporating a benzo[1,2-b:4,5-b']dithiophene
      (BDT) unit as conjugated spacer has been synthesized and successfully used for
      dye-sensitized solar cells (DSSCs). The length of the pi-conjugated spacers has a
      strong impact on electro-optical properties of these dyes, leading to the
      conversion efficiencies ranging from 4.17 to 5.68% under AM 1.5 G irradiation.
      This result indicates that the BDT unit is a promising candidate in organic
      sensitizers.

PMID- 21958085
TI  - Heterogeneity of disease and clones of community-onset methicillin-resistant
      Staphylococcus aureus in children attending a paediatric hospital in Belgium.
AB  - The increase in the number of methicillin-resistant Staphylococcus aureus (MRSA)
      infections in children has prompted paediatricians to broaden th empirical
      treatment of common community-onset (CO) infections in children in several
      countries. Most European countries have reported low rates of CO-MRSA infection,
      but limited data on paediatric CO-MRSA infections are available. A prospective
      study was conducted from January 2002 to December 2004 in Brussels. CO-MRSA was
      defined as MRSA first detected by culture within 48 h of admission or in
      outpatients. Clinical and epidemiological data were recorded. CO-MRSA strains
      were genotyped by pulsed-field gel electrophoresis and multilocus sequence
      typing. Staphylococcal chromosomal cassette mec, toxin (Panton-Valentin
      leukocidin (PVL), toxic shock syndrome toxin 1, and Eta/b), enterotoxin and
      antibiotic resistance genes were detected by PCR. The antibiotic resistance
      phenotype was determined by disk diffusion. S. aureus was isolated in 1681
      children. Among these, 107 harboured MRSA. Fifty-one children were colonized or
      infected by CO-MRSA, 20% of whom had no healthcare exposure. Twelve infants <3
      months old and five cystic fibrosis patients were colonized. None of the 22
      infected patients (59% with acute otitis media and 36% with skin and soft tissue
      infections (SSTIs)) required hospitalization. Two-thirds of them failed to
      respond to empirical antibiotic therapy. The 37 characterized CO-MRSA strains
      were genetically diverse. Most of them had healthcare-associated genotypes. Only
      six strains were PVL-positive, all of which were ciprofloxacin-susceptible and
      more common in children with SSTIs (p 0.001). CO-MRSA remains uncommon in our
      paediatric population. So far, there is no need to modify the empirical treatment
      of common S. aureus infections. Monitoring of MRSA rates in S. aureus CO
      infections remains mandatory, and further investigation is warranted to establish
      the source of colonization in young infants.

PMID- 21958090
TI  - Functional characterization of an NADPH dependent 2-alkyl-3-ketoalkanoic acid
      reductase involved in olefin biosynthesis in Stenotrophomonas maltophilia.
AB  - OleD is shown to play a key reductive role in the generation of alkenes (olefins)
      from acyl thioesters in Stenotrophomonas maltophilia. The gene coding for OleD
      clusters with three other genes, oleABC, and all appear to be transcribed in the
      same direction as an operon in various olefin producing bacteria. In this study,
      a series of substrates varying in chain length and stereochemistry were
      synthesized and used to elucidate the functional role and substrate specificity
      of OleD. We demonstrated that OleD, which is an NADP(H) dependent reductase, is a
      homodimer which catalyzes the reversible stereospecific reduction of 2-alkyl-3
      ketoalkanoic acids. Maximal catalytic efficiency was observed with syn-2-decyl-3
      hydroxytetradecanoic acid, with a k(cat)/K(m) 5- and 8-fold higher than for syn-2
      octyl-3-hydroxydodecanoic acid and syn-2-hexyl-3-hydroxydecanoic acid,
      respectively. OleD activity was not observed with syn-2-butyl-3-hydroxyoctanoic
      acid and compounds lacking a 2-alkyl group such as 3-ketodecanoic and 3
      hydroxydecanoic acids, suggesting the necessity of the 2-alkyl chain for enzyme
      recognition and catalysis. Using diastereomeric pairs of substrates and 4
      enantiopure isomers of 2-hexyl-3-hydroxydecanoic acid of known stereochemistry,
      OleD was shown to have a marked stereochemical preference for the (2R,3S)-isomer.
      Finally, experiments involving OleA and OleD demonstrate the first 3 steps and
      stereochemical course in olefin formation from acyl thioesters; condensation to
      form a 2-alkyl-3-ketoacyl thioester, subsequent thioester hydrolysis, and ketone
      reduction.

PMID- 21958091
TI  - Quality-of-life assessment in schizophrenia: the unfulfilled promise.

PMID- 21958092
TI  - Unsupported off-label use of cancer therapies: new challenges in the era of
      biopharmaceuticals.

PMID- 21958094
TI  - Economic modeling of the relationship between insurance, inequality and health.
AB  - In June 2011, the conference entitled 'Insurance. Inequality. Health. Economic
      modeling of how health insurance systems shape inequalities' took place in
      Darmstadt, Germany. The participants were researchers from all around the world.
      Presenters and distinguished invited speakers came together to discuss recent
      research results on various aspects of the health insurance system. The
      overarching aim was to clarify to what extent insurance markets, social insurance
      schemes, socioeconomic inequalities and health interact with each other.

PMID- 21958095
TI  - Are economic evaluations an important tool in vaccine policy decisions?
AB  - In the 1980s, drug prices began rising considerably worldwide, and in the 1990s,
      countries began incorporating health economics into the scientific review
      process. Rising prices in vaccines began around the year 2000 and national bodies
      began to use health economics to review vaccines in the next decade. Health
      economics is a discipline that evaluates alternative interventions, balancing
      costs and health outcomes. There are characteristics of infectious diseases that
      differ from other illnesses, most notably the herd effect. We reviewed the role
      of economics in conducting vaccine scientific reviews. We conclude that health
      economics can move some of the considerations in vaccine policy decision-making
      from the political to the scientific arena, but there are still many unresolved
      issues. Health economists will continue to address these issues in the coming
      years, but there will always be a need for a separate policy review.

PMID- 21958096
TI  - Using health technology assessment to support evidence-based decision-making in
      Canada: an academic perspective.
AB  - Health technology assessment (HTA) adopts a multidisciplinary approach to
      comprehensively assess safety, efficacy, effectiveness, economic and
      organizational impact, and any potential social and ethical implications
      associated with adoption and diffusion of a technology in a healthcare system.
      Canada was one of the first pioneers in using HTA as a research tool to support
      evidence-based decision-making. This article describes the current application of
      HTA in Canada, with a focus on some federal and Ontario initiatives in which the
      authors have extensive knowledge and experience to illustrate how academic
      researchers conduct HTA in collaboration with decision makers. Some issues and
      challenges are also highlighted that will hopefully stimulate a broader
      discussion among HTA stakeholders to move HTA forward.

PMID- 21958097
TI  - Quality of life following treatment for B-cell lymphoma.
AB  - Clinical outcome for B-cell non-Hodgkin's lymphoma has been greatly improved
      through the combination of new treatment options, in particular noncytotoxic
      drugs that specifically target disease mechanisms. Furthermore, in many cases,
      lymphoma survivors have to cope with long-term toxicity. Therefore, as with
      survival and remission length, the assessment of quality of life (QoL) is a major
      consideration when judging therapeutic benefit in patients. The aim of this
      article is to discuss the impact of widespread treatments on QoL and the
      relevance of QoL assessment in B-cell non-Hodgkin's lymphoma in day-to-day
      clinical practice. Additional studies of QoL in the general population, the
      associations between QoL and treatment strategy, QoL and specific situations
      (i.e., stem-cell transplantation and aging population) are also considered.

PMID- 21958098
TI  - A literature review of symptom clusters in patients with breast cancer.
AB  - The aim of this article is to present a review reporting empirically determined
      symptom clusters in breast cancer patients. We conducted a literature search on
      symptom clusters in breast cancer patients using PubMed, MEDLINE, EMBASE and
      CINAHL. Studies examining the presence of predetermined clusters were excluded.
      The five relevant studies identified were published between 2005 and 2009. The
      five studies differed from each other by statistical methodology, by the number
      of symptom clusters produced and by the symptoms comprising the clusters. Symptom
      clusters extracted between the five studies varied from one to four, while the
      number of symptoms in a cluster ranged from two to five. One study examining
      symptom clusters between different patient groups and a second study examining
      clusters across a time trajectory had certain reproducible clusters comprising
      similar symptoms. There were no clusters across different studies that contained
      the same symptoms, although the single symptom of fatigue was present in a
      cluster in all five studies and depression/psychological distress was noted in
      four of the studies. Nausea and appetite were the only two symptoms that
      associated together across three of the five studies; however, they were not the
      only two symptoms in those clusters. Methodological disparities include different
      patient populations between and within studies, different statistical methods,
      varying assessment tools and time points, with the majority of studies employing
      more than one symptom tool. Although there were common symptoms assessed across
      the five studies, no common symptom clusters could be derived from these reports.
      This lack of commonality may result from the disparities in subpopulations of
      patients, assessment tools, and analytical and methodological approaches. As
      symptom cluster research continues to develop towards a clearer consensus on
      guidelines, the findings of symptom clusters may provide clinically valuable
      information regarding diagnosis, prognostication, prioritizing and managing
      symptoms in breast cancer patients.

PMID- 21958099
TI  - Comparison of the EORTC QLQ-C15-PAL and the FACIT-Pal for assessment of quality
      of life in patients with advanced cancer.
AB  - Shorter quality-of-life (QoL) assessments are beneficial for palliative patients
      as they reduce burden associated with completing personal, and at times
      stressful, questionnaires. The European Organisation for Research and Treatment
      of Cancer Quality of Life Questionnaire Core 15 Palliative (QLQ-C15-PAL) and the
      Functional Assessment of Chronic Illness Therapy - Palliative Care (FACIT-Pal)
      are two palliative QoL tools that have been validated for use in this population.
      The purpose of this article was to conduct a review of studies utilizing these
      two palliative-specific QoL instruments, their development and their relative
      strengths for use in advanced cancer patients. Studies detailing the development
      process for the QLQ-C15-PAL and the FACIT-Pal were identified. A comparison
      between both questionnaires in terms of development, characteristics, validation
      and use was conducted. The QLQ-C15-PAL was developed via structured shortening of
      the longer core instrument, the Quality of Life Questionnaire Core 30 (QLQ-C30),
      whereas the FACIT-Pal includes the Functional Assessment of Cancer Therapy -
      General tool plus a new 19-item palliative scale created through interviews with
      patients and healthcare professionals. Although significant overlap exists
      between both tools, there is a marked difference in the aspects of QoL assessed.
      Scoring, organization and item format are different; however, response options
      and recall period are the same. Both tools cover the core items relevant to
      patients with advanced cancers and can be supplemented with disease-specific
      tools. Both QLQ-C15-PAL and FACIT-Pal allow for assessment of QoL issues specific
      to patients with advanced diseases. Each instrument has unique strengths and
      weaknesses and choice between these tools is dependent on the investigator and
      study needs. Future studies should directly compare these two tools and validate
      their use through a number of administration modes.

PMID- 21958100
TI  - Impact of response shift on longitudinal quality-of-life assessment in cancer
      clinical trials.
AB  - The assessment of longitudinal change in subjective patient-reported outcomes
      such as health-related quality of life (HRQoL) is a key component of many
      clinical and research evaluations. A major goal of measuring patient-reported
      HRQoL is to determine to what extent changes in HRQoL reports over time represent
      true changes in HRQoL due to treatment or cancer and to what extent they reflect
      measurement error. Indeed, the subjective assessment of HRQoL change is subject
      to response-shift effects, whereby health changes lead to shifts in internal
      standards (i.e., 'recalibration'), values (i.e., 'reprioritization') and
      conceptualization (i.e., 'reconceptualization') of key HRQoL domains. Response
      shift is a naturally occurring process that could distort the interpretation of
      change in HRQoL scores over time in interventional studies. Assessing response
      shift may therefore be needed to obtain a valid and sensitive assessment of
      change over time. Several methods to detect and measure the size and the
      direction of response shift are available. In this article, we summarize the
      methods used to assess and adjust for the response-shift effect in clinical
      trials. Nevertheless, our understanding of the parameters and processes
      associated with response shift is very limited. Further research is still needed
      to better understand how to measure the different components of response shift
      and how to take them into account in cancer research.

PMID- 21958101
TI  - The use of real-time patient-reported outcomes and quality-of-life data in
      oncology clinical practice.
AB  - The collection of patient-reported outcome (PRO) data such as quality of life
      (QoL) has provided important information in clinical trials. Increasingly,
      researchers are evaluating the use of this type of data in the clinical setting.
      The benefits of PRO/QoL data collection, methods for collecting data and the use
      of the data by clinicians are increasingly being studied. This article will
      address the issues and benefits of QoL and other PRO data collection within
      oncology clinical practice.

PMID- 21958102
TI  - Rating scales and Rasch measurement.
AB  - Assessments with ratings in ordered categories have become ubiquitous in health,
      biological and social sciences. Ratings are used when a measuring instrument of
      the kind found in the natural sciences is not available to assess some property
      in terms of degree - for example, greater or smaller, better or worse, or
      stronger or weaker. The handling of ratings has ranged from the very elementary
      to the highly sophisticated. In an elementary form, and assumed in classical test
      theory, the ratings are scored with successive integers and treated as
      measurements; in a sophisticated form, and used in modern test theory, the
      ratings are characterized by probabilistic response models with parameters for
      persons and the rating categories. Within modern test theory, two paradigms,
      similar in many details but incompatible on crucial points, have emerged. For the
      purposes of this article, these are termed the statistical modeling and
      experimental measurement paradigms. Rather than reviewing a compendium of
      available methods and models for analyzing ratings in detail, the article focuses
      on the incompatible differences between these two paradigms, with implications
      for choice of model and inferences. It shows that the differences have
      implications for different roles for substantive researchers and psychometricians
      in designing instruments with rating scales. To illustrate these differences, an
      example is provided.

PMID- 21958103
TI  - Examining the relationships among health-related quality-of-life indicators in
      cancer patients participating in clinical trials: a pooled study of baseline
      EORTC QLQ-C30 data.
AB  - AIMS: Cancer patients experience multiple and concurrent health-related problems
      and symptoms due to their illness and therapies. The first objective of this
      analysis was to identify how health-related quality-of-life (HRQoL) indicators
      cluster among cancer patients and how possible clusters change across patients
      with different sociodemographic and clinical characteristics. The second
      objective of this study was to identify which HRQoL indicators are linked to
      patients' perception of overall quality of life. METHODS: Retrospective pooling
      of 30 closed randomized European Organisation for Research and Treatment of
      Cancer (EORTC) clinical trials yielded baseline EORTC Quality of Life Core
      Questionnaire (QLQ-C30) HRQoL data for a total of 7417 patients. A cluster
      analysis was performed to determine how the 15 HRQoL indicators obtained with the
      QLQ-C30 cluster overall and by patient characteristics. RESULTS: Three main
      clusters emerged from the overall dataset: a physical cluster, a psychological
      cluster and a gastrointestinal cluster. The same clusters were found in subgroups
      defined according to sociodemographic and clinical characteristics, while some
      differences emerged among cancer sites. The Global Health scale was found to be
      part of the physical cluster in the overall dataset. This result was consistent
      across different levels of disease severity, while divergent results were seen
      across some cancer sites. CONCLUSION: Our findings suggest that HRQoL indicators
      are interrelated. Understanding these relationships may aid clinicians in
      managing the symptom burden experienced by patients, as well as policy-makers, in
      defining psychosocial support plans.

PMID- 21958104
TI  - Cost-effectiveness of rivaroxaban versus heparins for prevention of venous
      thromboembolism after total hip or knee surgery in Sweden.
AB  - AIMS: The objective of this study was to evaluate the cost-effectiveness of
      rivaroxaban versus the low-molecular-weight heparins (LMWH) enoxaparin and
      dalteparin for the prevention of venous thromboembolism (VTE) after total hip
      replacement and total knee replacement in Sweden. METHODS: The model included
      acute venous thromboembolic events and long-term complications over a 5-year time
      horizon represented by an acute and a chronic phase with 1-year cycles.
      Transition probabilities were derived from the Regulation of Coagulation in
      Orthopaedic Surgery to Prevent Deep Vein Thrombosis and Pulmonary Embolism
      (RECORD) clinical trials. RESULTS: In patients undergoing total hip replacement,
      the incremental cost per additional quality-adjusted life-year of extended
      prophylaxis for 35 days with rivaroxaban versus 14 days of prophylaxis with
      enoxaparin or dalteparin was SEK29,400 and SEK35,400, respectively. In total knee
      replacement patients, 14 days of rivaroxaban dominated 14 days of LMWH as
      prophylaxis for VTE. CONCLUSION: The results of the economic model consistently
      showed that, over a 5-year period, rivaroxaban is a cost-effective alternative to
      14 days of LMWH for VTE prophylaxis in Sweden.

PMID- 21958106
TI  - Site-selective, cleavable linkers: quality control and the characterization of
      small molecules on microelectrode arrays.
AB  - A "safety-catch" linker strategy has been used to release a portion of the
      products of a Diels-Alder reaction conducted on a microelectrode array for
      characterization of stereochemistry. The attachment and cleavage of organic
      compounds from the surface of selected electrodes in the array can be
      accomplished by site-selective generation of base or acid at the electrode. It
      was found that the surface of the array had a minor influence on the
      stereochemistry of the Diels-Alder reaction, leading to slightly more of the exo
      product relative to a similar solution-phase reaction.

PMID- 21958107
TI  - Hole tunneling and hopping in a Ru(bpy)3(2+)-phenothiazine dyad with a bridge
      derived from oligo-p-phenylene.
AB  - A molecular dyad was synthesized in which a Ru(bpy)(3)(2+) (bpy = 2,2'
      bipyridine) photosensitizer and a phenothiazine redox partner are bridged by a
      sequence of tetramethoxybenzene, p-dimethoxybenzene, and p-xylene units. Hole
      transfer from the oxidized metal complex to the phenothiazine was triggered using
      a flash-quench technique and investigated by transient absorption spectroscopy.
      Optical spectroscopic and electrochemical experiments performed on a suitable
      reference molecule in addition to the above-mentioned dyad lead to the conclusion
      that hole transfer from Ru(bpy)(3)(3+) to phenothiazine proceeds through a
      sequence of hopping and tunneling steps: Initial hole hopping from Ru(bpy)(3)(3+)
      to the easily oxidizable tetramethoxybenzene unit is followed by tunneling
      through the barrier imposed by the p-dimethoxybenzene and p-xylene spacers. The
      overall charge transfer proceeds with a time constant of 41 ns, which compares
      favorably to a time constant of 1835 ns associated with equidistant hole
      tunneling between the same donor-acceptor couple bridged by three identical p
      xylene units. The combined hopping/tunneling sequence thus leads to an
      acceleration of hole transfer by roughly a factor of 50 when compared to a pure
      tunneling mechanism.

PMID- 21958108
TI  - Efficient traversal of beta-sheet protein folding pathways using ensemble models.
AB  - Molecular dynamics (MD) simulations can now predict ms-timescale folding
      processes of small proteins; however, this presently requires hundreds of
      thousands of CPU hours and is primarily applicable to short peptides with few
      long-range interactions. Larger and slower-folding proteins, such as many with
      extended beta-sheet structure, would require orders of magnitude more time and
      computing resources. Furthermore, when the objective is to determine only which
      folding events are necessary and limiting, atomistic detail MD simulations can
      prove unnecessary. Here, we introduce the program tFolder as an efficient method
      for modelling the folding process of large beta-sheet proteins using sequence
      data alone. To do so, we extend existing ensemble beta-sheet prediction
      techniques, which permitted only a fixed anti-parallel beta-barrel shape, with a
      method that predicts arbitrary beta-strand/beta-strand orientations and strand
      order permutations. By accounting for all partial and final structural states, we
      can then model the transition from random coil to native state as a Markov
      process, using a master equation to simulate population dynamics of folding over
      time. Thus, all putative folding pathways can be energetically scored, including
      which transitions present the greatest barriers. Since correct folding pathway
      prediction is likely determined by the accuracy of contact prediction, we
      demonstrate the accuracy of tFolder to be comparable with state-of-the-art
      methods designed specifically for the contact prediction problem alone. We
      validate our method for dynamics prediction by applying it to the folding pathway
      of the well-studied Protein G. With relatively very little computation time,
      tFolder is able to reveal critical features of the folding pathways which were
      only previously observed through time-consuming MD simulations and experimental
      studies. Such a result greatly expands the number of proteins whose folding
      pathways can be studied, while the algorithmic integration of ensemble prediction
      with Markovian dynamics can be applied to many other problems.

PMID- 21958109
TI  - Connecting the dots: responses of coastal ecosystems to changing nutrient
      concentrations.
AB  - Empirical relationships between phytoplankton biomass and nutrient concentrations
      established across a wide range of different ecosystems constitute fundamental
      quantitative tools for predicting effects of nutrient management plans. Nutrient
      management plans based on such relationships, mostly established over trends of
      increasing rather than decreasing nutrient concentrations, assume full
      reversibility of coastal eutrophication. Monitoring data from 28 ecosystems
      located in four well-studied regions were analyzed to study the generality of
      chlorophyll a versus nutrient relationships and their applicability for ecosystem
      management. We demonstrate significant differences across regions as well as
      between specific coastal ecosystems within regions in the response of chlorophyll
      a to changing nitrogen concentrations. We also show that the chlorophyll a versus
      nitrogen relationships over time constitute convoluted trajectories rather than
      simple unique relationships. The ratio of chlorophyll a to total nitrogen almost
      doubled over the last 30-40 years across all regions. The uniformity of these
      trends, or shifting baselines, suggest they may result from large-scale changes,
      possibly associated with global climate change and increasing human stress on
      coastal ecosystems. Ecosystem management must, therefore, develop adaptation
      strategies to face shifting baselines and maintain ecosystem services at a
      sustainable level rather than striving to restore an ecosystem state of the past.

PMID- 21958111
TI  - Photophysics of untethered ZnTPP-fullerene complexes in solution.
AB  - The spectroscopy and dynamic behavior of the self-assembled, Soret-excited zinc
      tetraphenylporphyrin (ZnTPP) plus fullerene (C(60)) model system in solution has
      been examined using steady state fluorescence quenching, nanosecond time
      correlated single photon counting, picosecond fluorescence upconversion, and
      picosecond transient absorption methods. Evidence of ground state complexation is
      presented. Steady-state quenching of the S(2) and S(1) fluorescence of ZnTPP by
      C(60) reveals that the quenching processes only occur in the excited complexes,
      are ultrafast, and proceed at different rates in the two states. Only uncomplexed
      ZnTPP is observed by fluorescence lifetime methods; the locally excited complexes
      are either dark or, more likely, rapidly relax to products that do not radiate
      strongly. Both short-range (Dexter) energy transfer and electron transfer
      relaxation mechanisms are evaluated. Picosecond transient absorption data
      obtained from the subtle differences between the spectra of Soret-excited ZnTPP
      with and without a large excess of added C(60) reveal the formation, on a
      subpicosecond time scale, of relatively long-lived charge-separated species.
      Soret excitation of ZnTPP...C(60) does not produce a quantitative yield of
      species in the lower S(1) excited state.

PMID- 21958110
TI  - Factors associated with chemical burns in Zhejiang province, China: an
      epidemiological study.
AB  - BACKGROUND: Work-related burns are common among occupational injuries. Zhejiang
      Province is an industrial area with a high incidence of chemical burns. We aimed
      to survey epidemiological features of chemical burns in Zhejiang province to
      determine associated factors and acquire data for developing a strategy to
      prevent and treat chemical burns. METHODS: Questionnaires were developed,
      reviewed and validated by experts, and sent to 25 hospitals in Zhejiang province
      to prospectively collect data of 492 chemical burn patients admitted during one
      year from Sept. 1, 2008 to Aug. 31, 2009. Questions included victims'
      characteristics and general condition, injury location, causes of accident,
      causative chemicals, total body surface area burn, concomitant injuries, employee
      safety training, and awareness level of protective measures. Surveys were
      completed for each of burn patients by burn department personnel who interviewed
      the hospitalized patients. RESULTS: In this study, 417 victims (87.61%) got
      chemical burn at work, of which 355 victims (74.58%) worked in private or
      individual enterprises. Most frequent chemicals involved were hydrofluoric acid
      and sulfuric acid. Main causes of chemical injury accidents were inappropriate
      operation of equipment or handling of chemicals and absence of or failure to use
      effective individual protection. CONCLUSIONS: Most chemical burns are preventable
      occupational injuries that can be attributed to inappropriate operation of
      equipment or handling of chemicals, lack of employee awareness about appropriate
      action and lack of effective protective equipment and training. Emphasis on
      safety education and protection for workers may help protect workers and prevent
      chemical burns.

PMID- 21958112
TI  - High degree of sex chromosome differentiation in stickleback fishes.
AB  - BACKGROUND: Studies of closely related species with different sex chromosome
      systems can provide insights into the processes of sex chromosome differentiation
      and evolution. To investigate the potential utility of molecular markers in
      studying sex chromosome differentiation at early stages of their divergence, we
      examined the levels and patterns of genetic differentiation between sex
      chromosomes in nine-spined (Pungitius pungitius) and three-spined sticklebacks
      (Gasterosteus aculeatus) using microsatellite markers. RESULTS: A set of novel
      microsatellite markers spanning the entire length of the sex chromosomes were
      developed for nine-spined sticklebacks using the sequenced genomes of other fish
      species. Sex-specific patterns of genetic variability and male-specific alleles
      were identified at most of these loci, indicating a high degree of
      differentiation between the X and Y chromosomes in nine-spined sticklebacks. In
      three-spined sticklebacks, male-specific alleles were detected at some loci
      confined to two chromosomal regions. In addition, male-specific null alleles were
      identified at several other loci, implying the absence of Y chromosomal alleles
      at these loci. Overall, male-specific alleles and null alleles were found over a
      region spanning 81% of the sex chromosomes in three-spined sticklebacks.
      CONCLUSIONS: High levels but distinct patterns of sex chromosome differentiation
      were uncovered in the stickleback species that diverged 13 million years ago. Our
      results suggest that the Y chromosome is highly degenerate in three-spined
      sticklebacks, but not in nine-spined sticklebacks. In general, the results
      demonstrate that microsatellites can be useful in identifying the degree and
      patterns of sex chromosome differentiation in species at initial stages of sex
      chromosome evolution.

PMID- 21958113
TI  - Molecular dynamics simulations of the adsorption of bone morphogenetic protein-2
      on surfaces with medical relevance.
AB  - Bone morphogenetic protein-2 (BMP-2) plays a crucial role in osteoblast
      differentiation and proliferation. Its effective therapeutic use for ectopic bone
      and cartilage regeneration depends, among other factors, on the interaction with
      the carrier at the implant site. In this study, we used classical molecular
      dynamics (MD) and a hybrid approach of steered molecular dynamics (SMD) combined
      with MD simulations to investigate the initial stages of the adsorption of BMP-2
      when approaching two implant surfaces, hydrophobic graphite and hydrophilic
      titanium dioxide rutile. Surface adsorption was evaluated for six different
      orientations of the protein, two end-on and four side-on, in explicit water
      environment. On graphite, we observed a weak but stable adsorption. Depending on
      the initial orientation, hydrophobic patches as well as flexible loops of the
      protein were involved in the interaction with graphite. On the contrary, BMP-2
      adsorbed only loosely to hydrophilic titanium dioxide. Despite a favorable
      interaction energy between protein and the TiO(2) surface, the rapid formation of
      a two-layer water structure prevented the direct interaction between protein and
      titanium dioxide. The first water adlayer had a strong repulsive effect on the
      protein, while the second attracted the protein toward the surface. For both
      surfaces, hydrophobic graphite and hydrophilic titanium dioxide, denaturation of
      BMP-2 induced by adsorption was not observed on the nanosecond time scale.

PMID- 21958114
TI  - A toxicity study of multiple-administration human umbilical cord mesenchymal stem
      cells in cynomolgus monkeys.
AB  - Therapies based on stem cells have shown very attractive potential in many
      clinical studies. However, the data about the safety of stem cells application
      remains insufficient. The present study was designed to evaluate the overall
      toxicology of human umbilical cord mesenchymal stem cells (hUC-MSCs) in
      cynomolgus monkeys with repeated administrations. hUC-MSCs were administered by
      intravenous injection once every 2 weeks for 6 weeks. The dose levels employed in
      this study were 2*10(6), 1*10(7) cells/kg body weight. Toxicity was evaluated by
      clinical observations (body weight, body temperature, and ophthalmology exams),
      pathology (blood cell counts, clinical biochemistry, urinalysis, and bone marrow
      smears), immunologic consequences (lymphoproliferation assay, the secretion of
      interferon-gamma and interleukin-4, the percentage of CD3, CD4, CD8 T cells, and
      the ratio of CD4 and CD8 T cells) and anatomic pathology. Pharmacodynamics in
      blood and distribution of hUC-MSCs in the tissues of cynomolgus monkeys were
      measured by real-time polymerase chain reaction. All animals survived until
      scheduled euthanasia. No stem cells transplantation-related toxicity was found in
      this study. hUC-MSCs could be found in the blood of cynomolgus monkeys beyond 8
      h. The findings of this 6-week toxicity study showed that the transplantation of
      hUC-MSCs did not affect the general health of cynomolgus monkeys.

PMID- 21958115
TI  - The CBS domain: a protein module with an emerging prominent role in regulation.
AB  - Regulatory CBS (cystathionine beta-synthase) domains exist as two or four tandem
      copies in thousands of cytosolic and membrane-associated proteins from all
      kingdoms of life. Mutations in the CBS domains of human enzymes and membrane
      channels are associated with an array of hereditary diseases. Four CBS domains
      encoded within a single polypeptide or two identical polypeptides (each having a
      pair of CBS domains at the subunit interface) form a highly conserved disk-like
      structure. CBS domains act as autoinhibitory regulatory units in some proteins
      and activate or further inhibit protein function upon binding to adenosine
      nucleotides (AMP, ADP, ATP, S-adenosyl methionine, NAD, diadenosine
      polyphosphates). As a result of the differential effects of the nucleotides, CBS
      domain-containing proteins can sense cell energy levels. Significant
      conformational changes are induced in CBS domains by bound ligands, highlighting
      the structural basis for their effects.

PMID- 21958116
TI  - A metabolomic approach differentiates between conventional and organic ketchups.
AB  - The agronomic environments in which tomatoes are cultivated potentially affect
      the levels of antioxidants and other metabolites in commercial products. In this
      study, biochemical and metabolomic techniques were used to assess the differences
      between ketchups produced by organic and conventional systems. An untargeted
      metabolomic approach using QToF-MS was used to identify those nutrients that have
      the greatest impact on the overall metabolomic profile of organic ketchups as
      compared to conventional ones. Individual polyphenols were quantified using LC
      ESI-QqQ. This multifaceted approach revealed that the agronomic environment in
      which tomatoes are grown induces alterations in the content of antioxidant
      capacity, phenolics, and other metabolites in ketchups. Organic cultivation was
      found to provide tomatoes and tomato-derived products with a significantly higher
      content of antioxidant microconstituents, whereas glutamylphenylalanine and N
      malonyltryptophan were detected only in conventional ketchups.

PMID- 21958117
TI  - Increase in allergen-specific IgE and ex vivo Th2 responses after a single
      bronchial challenge with house dust mite in allergic asthmatics.
AB  - BACKGROUND:   Airway responsiveness to allergen in patients with allergic asthma
      is studied by bronchial allergen challenge. Although the typical features of the
      early and late responses on lung function and bronchial inflammation after
      allergen challenge are well known, little has been reported as yet on any changes
      in systemic allergic and immunologic parameters after 4-6 weeks. METHODS:   In a
      clinical study, 27 subjects with allergic asthma and house dust mite (HDM)
      allergy underwent a bronchial allergen challenge with HDM. Blood samples were
      collected before and 5 weeks after allergen challenge. Serum levels of total IgE
      and allergen-specific IgE were measured, and peripheral blood mononuclear cells
      were isolated and stimulated ex vivo with HDM to determine the allergen-specific
      T-cell cytokine response. RESULTS:   Five weeks after bronchial allergen
      challenge with HDM, the amount of circulating IgE against HDM and the major
      allergenic components Der p1 and Der p2 was significantly increased (10.8% and
      8.8%, respectively). IgE antibodies against other environmental allergens
      decreased (grass pollen) or remained unchanged (cat dander). Allergen-induced Th2
      cytokine production was also significantly increased (P< 0.001, P=0.014, and
      P=0.006 for IL-4, IL-5, and IL-13, respectively). The increase in Der p1- and Der
      p2-specific IgE in serum correlated with increased numbers of Th2-cytokine
      producing cells (Rs=0.56, P=0.002 and Rs=0.54, P=0.004 for IL-4 and IL-13,
      respectively). CONCLUSIONS:   A single bronchial allergen challenge with HDM is
      accompanied by increased levels of allergen-specific IgE for HDM in serum and an
      enhanced Th2 response to HDM still detectable 5 weeks after challenge.

PMID- 21958118
TI  - Promiscuity of carbonic anhydrase II. Unexpected ester hydrolysis of carbohydrate
      based sulfamate inhibitors.
AB  - Carbonic anhydrases (CAs) are enzymes whose endogenous reaction is the reversible
      hydration of CO(2) to give HCO(3)(-) and a proton. CA are also known to exhibit
      weak and promiscuous esterase activity toward activated esters. Here, we report a
      series of findings obtained with a set of CA inhibitors that showed quite
      unexpectedly that the compounds were both inhibitors of CO(2) hydration and
      substrates for the esterase activity of CA. The compounds comprised a
      monosaccharide core with the C-6 primary hydroxyl group derivatized as a
      sulfamate (for CA recognition). The remaining four sugar hydroxyl groups were
      acylated. Using protein X-ray crystallography, the crystal structures of human CA
      II in complex with four of the sulfamate inhibitors were obtained. As expected,
      the four structures displayed the canonical CA protein-sulfamate interactions.
      Unexpectedly, a free hydroxyl group was observed at the anomeric center (C-1)
      rather than the parent C-1 acyl group. In addition, this hydroxyl group is
      observed axial to the carbohydrate ring while in the parent structure it is
      equatorial. A mechanism is proposed that accounts for this inversion of
      stereochemistry. For three of the inhibitors, the acyl groups at C-2 or at C-2
      and C-3 were also absent with hydroxyl groups observed in their place and
      retention of stereochemistry. With the use of electrospray ionization-Fourier
      transform ion cyclotron resonance-mass spectrometry (ESI-FTICR-MS), we observed
      directly the sequential loss of all four acyl groups from one of the carbohydrate
      based sulfamates. For this compound, the inhibitor and substrate binding mode
      were further analyzed using free energy calculations. These calculations
      suggested that the parent compound binds almost exclusively as a substrate. To
      conclude, we have demonstrated that acylated carbohydrate-based sulfamates are
      simultaneously inhibitor and substrate of human CA II. Our results suggest that,
      initially, the substrate binding mode dominates, but following hydrolysis, the
      ligand can also bind as a pure inhibitor thereby competing with the substrate
      binding mode.

PMID- 21958119
TI  - Low-dose dietary resveratrol has differential effects on colorectal tumorigenesis
      in adiponectin knockout and wild-type mice.
AB  - Obesity is associated with a decrease in the antiinflammatory hormone,
      adiponectin, and increases in the circulating concentrations of multiple
      proinflammatory cytokines. These changes contribute to colon tumorigenesis.
      Resveratrol increases adiponectin production in adipocytes and attenuates the
      development of colon cancer. Thus, we hypothesized that adiponectin is an
      integral component of the mechanism by which resveratrol antagonizes colorectal
      tumorigenesis. To investigate this, we induced tumorigenesis in adiponectin
      knockout (KO) and wild-type (Wt) C57BL/6 mice through combined azoxymethane and
      dextran sodium sulfate treatment during which mice were fed a high-fat, lard
      based diet, or the same diet containing 20 mg/kg resveratrol. After 14 wk on
      diet, Wt mice gained more weight and, on a percentage basis, had higher fat mass
      and lower lean mass than KO mice. Resveratrol tended to attenuate this response
      in male Wt mice. Resveratrol also tended to reduce aberrant crypt foci
      development and decrease circulating interleukin 6 and insulin concentrations in
      male but not female Wt mice. Taken together, resveratrol improved overall health
      of obese Wt but not KO mice as hypothesized with a differential sex response.

PMID- 21958120
TI  - Effects of nutritional cues on the duration of the winter anovulatory phase and
      on associated hormone levels in adult female Welsh pony horses (Equus caballus).
AB  - BACKGROUND: Mares have an annual reproductive rhythm, with a phase of inactivity
      in midwinter. The aim of this study was to determine the impact of food
      restriction on physiological and metabolic hallmarks of this rhythm. METHODS:
      Over three successive years, 3 groups of 10 mares were kept under natural
      photoperiod. A 'well-fed' group was fed to maintain the mares in good body
      condition; a 'restricted' group received a diet calculated to keep the mares thin
      and a 'variable' group was fed during some periods like the 'restricted' group
      and during some other periods like the 'well-fed' group, with the aim of
      mimicking the natural seasonal variation of pasture availability, but a few
      months in advance of this natural rhythm. RESULTS: Winter ovarian inactivity
      always occurred and was long in the restricted group. In contrast, in the 'well
      fed' group, 40% of mares showed this inactivity, which was shorter than in the
      other groups. Re-feeding the 'variable' group in autumn and winter did not
      advance the first ovulation in spring, compared with the 'restricted' group.
      Measurements of glucose and insulin concentrations in mares from the 'restricted'
      group during two 24 h periods of blood sampling, revealed no post-prandial peaks.
      For GH (Growth hormone), IGF-1 and leptin levels, large differences were found
      between the 'well-fed' group and the other groups. The glucose, insulin, GH and
      leptin levels but not melatonin level are highly correlated with the duration of
      ovulatory activity. CONCLUSIONS: The annual rhythm driven by melatonin secretion
      is only responsible for the timing of the breeding season. The occurrence and
      length of winter ovarian inactivity is defined by metabolic hormones.

PMID- 21958121
TI  - Proportion of patients at HbA1c target <7% with eight classes of antidiabetic
      drugs in type 2 diabetes: systematic review of 218 randomized controlled trials
      with 78 945 patients.
AB  - AIM: We assessed the efficacy of eight classes of diabetes medications used in
      current clinical practice [metformin, sulphonylureas, alpha-glucosidase
      inhibitors, thiazolidinediones, glinides, dipeptidyl peptidase-4 inhibitors,
      glucagon-like peptide-1 (GLP-1) analogues and insulin analogues] to reach the
      HbA1c target <7% in type 2 diabetes. METHODS: MEDLINE, EMBASE and the Cochrane
      CENTRAL were searched from inception through April 2011 for randomized controlled
      trials (RCTs) involving antidiabetic drugs. RCTs had to report the effect of any
      diabetes medication on the HbA1c levels, to include at least 30 subjects in every
      arm of the study, and to report the effect of therapy after a minimum of 12
      weeks. Data were summarized across studies using random-effects meta-regression.
      RESULTS: A total of 218 RCTs (339 arms and 77 950 patients) met the inclusion
      criteria. The proportion of patients who achieved the HbA1c goal ranged from
      25.9% (95% CI 18.5-34.9) with alpha-glucosidase inhibitors to 63.2% (54.1-71.5)
      with the long-acting GLP-1 analogue. There was a progressive decrease of the
      proportion of patients at target for each 0.5% increase in baseline HbA1c,
      ranging from 57.8% for HbA1c <=7.5% to 20.8% for HbA1c >=10% (p for trend
      <0.0001), with some difference between insulin and non-insulin drugs: for
      insulin, the proportion of patients at goal reached a plateau for basal HbA1c
      value >9.0% with no further decrease, whereas for non-insulin drugs the
      relationship was continuous without any evidence of plateau. CONCLUSIONS: There
      is a considerable variability with regard to attainment of HbA1c goal of <7%
      among the different classes of diabetes medications; baseline HbA1c is an
      important determinant of observed efficacy.

PMID- 21958122
TI  - Effects of prolonged water washing of tissue samples fixed in formalin on
      histological staining.
AB  - The effects of prolonged water washing after fixation for 48 h in 10% (v/v)
      phosphate-buffered neutral formalin on the quality of representative histological
      staining methods were evaluated using samples of liver, kidney, spleen and thymus
      collected from three male Crl:CD(SD)(IGS) rats and one male beagle dog. Because
      door-to-door courier services in Japan prohibit handling formalin, our goal was
      to confirm that formalin fixed wet tissue samples could be stored in tap water
      rather than formalin during transportation of the samples without decreasing the
      quality of their staining or immunohistochemistry. Each tissue sample was
      allocated randomly to one of three groups: 12 min, 3 days and 7 days of washing
      in running tap water; samples then were routinely embedded in paraffin and
      sectioned. The sections were stained with hematoxylin and eosin, periodic acid
      Schiff, azan, and the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method.
      Immunohistochemical staining for Factor VIII, ED-1 and CD3 also was assessed.
      Prolonged water washing for up to 7 days did not affect the morphology or
      stainability by standard histological methods, or the intensity and frequency of
      positive reactions using the TUNEL method. Only immunohistochemical staining of
      Factor VIII was altered in both the rat and dog sections after 7 days of water
      washing. The intensity of positive reactions of Factor VIII immunohistochemistry
      after 7 days water washing was still strong enough to detect microscopically.
      Therefore, prolonged water washing for up to 7 days after formalin fixation does
      not have seriously detrimental effects on the quality and characteristics of
      paraffin sections stained by various methods, including immunohistochemistry.

PMID- 21958123
TI  - Successful conversion from twice-daily to once-daily tacrolimus in liver
      transplantation: observational multicenter study.
AB  - BACKGROUND: Compliance with immunosuppressive therapy in liver transplant
      patients is critical to prevent acute organ rejection and/or late graft loss.
      Strategies to simplify the therapeutic regimen may improve adherence. AIM: To
      evaluate the safety and efficacy of conversion from a twice-daily to once-daily
      tacrolimus formulation in adult liver transplant patients. PATIENTS AND METHODS:
      This prospective observational multicenter study included 187 liver transplant
      patients with at least 10 months post-transplant follow-up, no rejection episodes
      in the last three months, and creatinine levels <2 mg/dL. Conversion from a twice
      daily to a once-daily formulation was based on a 1:1 proportion. RESULTS: Median
      age was 61 yr (range: 28-80 yr); 64% were men and 36% women. The main indications
      for liver transplant were alcoholic cirrhosis in 30%. Median conversion time was
      55 months (range: 10-215 months). Serum tacrolimus levels decreased at one month
      after conversion (pre-conversion levels = 5.4 +/- 3.0 ng/mL vs. post-conversion
      levels = 4.4 +/- 2.4 ng/mL, p = 0.013); however, these values normalized at six
      months post-conversion with no changes in liver function and rejection episodes
      were observed only in two patients. CONCLUSION: Conversion from a twice-daily to
      a once-daily tacrolimus formulation is a safe, effective strategy in the
      management of stable liver transplant patients.

PMID- 21958129
TI  - Fine-needle aspiration biopsy, ultrasound and BRAF(v600E) analysis - is this the
      best FNAB combination for most patients?.

PMID- 21958130
TI  - The polyphenol-rich extract from grape seeds inhibits platelet signaling pathways
      triggered by both proteolytic and non-proteolytic agonists.
AB  - Mechanisms involved in the reduction of blood platelet functions by various plant
      extract, including the grape seeds extract (rich in phenolic compounds, a mixture
      of about 95% oligomeric phenols; GSE) are still unclear. In the literature there
      are few papers describing studies on the effects of GSE on selected element of
      hemostasis. The aim of our study was to establish and compare the influence of
      GSE (at final dose of 0.625-50 ug/ml) and resveratrol (3,4',5 -
      trihydroxystilben), a phenolic compound synthesized in grapes and vegetables and
      presents in wine, which has been supposed to be beneficial for the prevention of
      cardiovascular events, on different steps of platelet activation. We measured the
      effects of GSE and resveratrol on platelet aggregation, the surface expression of
      P-selectin, platelet microparticle formation (PMP), and superoxide anion radicals
      ([Formula: see text]) production in blood platelets stimulated by TRAP and
      thrombin. P-selectin expression and PMP formation were measured by a flow
      cytometer. In gel-filtered platelets activated by thrombin or TRAP and treated
      with different concentrations of GSE (1.25-50 ug/ml) a significant decrease of P
      selectin expression, PMP formation and platelet aggregation was observed. GSE
      caused also a dose-dependent reduction of [Formula: see text] produced in
      platelets activated by TRAP or thrombin. Our present results indicate that GSE
      inhibits platelet signaling pathways trigged by both proteolytic (thrombin) and
      non-proteolytic agonist (TRAP). In the comparative studies, GSE was found to be
      more effective antiplatelet factor, than the solution of pure resveratrol. Thus,
      the polyphenol-rich extract from grape seeds can be useful as the protecting
      factor against cardiovascular diseases.

PMID- 21958131
TI  - Sequential chronic myelogenous leukemia, B-lineage lymphoma and erythroleukemia
      with monosomy 7 over 10 years.

PMID- 21958132
TI  - Characterization of the side-chain hydroxyl moieties of residues Y56, Y111, Y238,
      Y338, and S339 as determinants of specificity in E. coli cystathionine beta
      lyase.
AB  - Cystathionine beta-lyase (CBL) catalyzes the hydrolysis of L-cystathionine (L
      Cth) to produce L-homocysteine, pyruvate, and ammonia. A series of site-directed
      variants of Escherichia coli CBL (eCBL) was constructed to investigate the roles
      of the hydroxyl moieties of active-site residues Y56, Y111, Y238, Y338, and S339
      as determinants of specificity. The effect of these conservative substitutions on
      the k(cat)/K(m)(L-Cth) for the alpha,beta-elimination of L-Cth ranges from a
      change of only 1.1-fold for Y338F to a reduction of 3 orders of magnitude for the
      alanine replacement variant of S339. A novel role for residue S339 as a
      determinant of reaction specificity, via tethering of the catalytic base, K210,
      is demonstrated. Comparison of the kinetic parameters for L-Cth hydrolysis with
      those for the inhibition of eCBL by aminoethoxyvinylglycine (AVG) indicates that
      Y238 interacts with the distal carboxylate group of the substrate. The 22 and 50
      fold increases in the K(m)(L-Cth) and K(i)(AVG) resulting from replacement of Y56
      with phenylalanine suggest that this residue may interact with the distal amino
      group of these compounds, although an indirect role in binding is more likely.
      The near-native k(cat)/K(m)(L-Cth) and pH profile of the eCBL-Y111F variant
      demonstrate that residue Y111 does not play a role in proton transfer. The
      understanding of the eCBL active site and of the determinants of substrate and
      reaction specificity resulting from this work will facilitate the design of
      inhibitors, as antibacterial therapeutics, and the engineering of enzymes
      dependent on the catalytically versatile pyridoxal 5'-phosphate cofactor to
      modify reaction specificity.

PMID- 21958133
TI  - Near-ultraviolet absorption cross sections of nitrophenols and their potential
      influence on tropospheric oxidation capacity.
AB  - Nitrophenols and methylnitrophenols have been identified as photolytic precursors
      of nitrous acid, HONO, but their gas-phase absorption has not previously been
      reported. In this study, the absorption cross sections of 2-nitrophenol, 3-methyl
      2-nitrophenol, and 4-methyl-2-nitrophenol were measured from 320 to 450 nm using
      incoherent broad-band cavity-enhanced absorption spectroscopy (IBBCEAS). The
      benzaldehyde absorption spectrum was measured to validate the approach and was in
      good agreement with literature spectra. The nitrophenol absorption cross sections
      are large (ca. 10(-17) cm(2) molecule(-1)) and blue-shifted about 20 nm compared
      to previously measured solution spectra. Besides forming HONO, nitrophenol
      absorption influences other photochemistry by reducing the available actinic
      flux. The magnitudes of both effects are evaluated as a function of solar zenith
      angle, and nitrophenol absorption is shown to lower the photolysis rates of O(3)
      and NO(2).

PMID- 21958135
TI  - Time to consider Clostridium probiotics?

PMID- 21958134
TI  - Tear total protein analysis in patients with late sulfur mustard-induced ocular
      complications: a cross-sectional study.
AB  - BACKGROUND: Eyes are the most sensitive organs to sulfur mustard (SM). Late
      ocular complications have been reported even 15-20 years post-exposure. To date,
      no study has investigated the composition of tear proteins in tear samples of SM
      intoxicated patients. METHODS: Total protein content as well as concentrations of
      vascular endothelial growth factor (VEGF), calcitonin gene related peptide (CGRP)
      and substance P were measured in unstimulated tears of chemically-injured
      patients who suffer from late ocular complications of SM. These levels were
      compared to corresponding values obtained from tears of healthy control subjects.
      The concentration of total proteins was measured using the Bradford method and
      those of VEGF, CGRP and substance P by ELISA. RESULTS: Total protein
      concentration was significantly lower in tears of the SM compared to control
      group (p<0.01). In contrast, tear samples of the SM group had significantly
      higher VEGF and VEGF/total protein compared to control group (p<0.01). Tear CGRP
      concentration was found to be lower in the SM vs. control group (p<0.05) but no
      significant difference in CGRP/total protein was observed (p>0.05). Finally, tear
      substance P concentrations were not found to be significantly different between
      the two groups (p>0.05). CONCLUSION: The results of this investigation indicated
      decreased total protein and CGRP, and elevated VEGF concentration in tears of SM
      intoxicated patients who suffer from chronic ocular complications.

PMID- 21958136
TI  - Advancements in using reporter DNAzymes for identifying pathogenic bacteria at
      speed and with convenience.

PMID- 21958138
TI  - Recent advances in probiotic research: a conference update.
AB  - The sixth IPC was held in Kosice; a nicely restored medieval city in eastern
      Slovakia. From being a Eastern-European-dominated probiotics conference in the
      year 2000, the IPC has grown over the years into a truly international
      conference, mainly on probiotics, but also increasingly prebiotics and the
      intestinal microbiota. The conference had contributions from participants from
      all continents. This article summarizes some of the highlights of the meeting.

PMID- 21958139
TI  - Update on invasive fungal disease.
AB  - One of the highlights of the antifungal sessions at the ECCMID-ICC congress was
      the presentation of the first European Society of Clinical Microbiology and
      Infectious Diseases (ESCMID) guideline for diagnostic and management for Candida
      diseases. Experts also discussed specific aspects of the management of invasive
      fungal disease in the intensive care unit and in hematological malignancy. Data
      from new clinical studies and from 'real life' experience of clinical use of
      antifungal therapy were also presented and discussed.

PMID- 21958140
TI  - Raman spectroscopy: lighting up the future of microbial identification.
AB  - Over the last decade Raman spectroscopy has become established as a
      physicochemical technique for the rapid identification of microbes. This powerful
      analytical method generates a spectroscopic fingerprint from the microbial
      sample, which provides quantitative and qualitative information that can be used
      to characterize, discriminate and identify microorganisms, in both bacteria
      slurry and at the single-cell level. Recent developments in Raman spectroscopy
      have dramatically increased in recent years due to the enhancement of the signal
      by techniques including tip-enhanced Raman spectroscopy and coherent anti-Stokes
      Raman spectroscopy and due to the availability of user-friendly instrumentation
      and software. The result of this has been reduced cost and rapid collection time,
      and it has allowed the nonspecialist access to this physical sciences approach
      for biological applications. In this article, we will briefly explain the
      technique of Raman spectroscopy and discuss enhancement techniques, including the
      recent application of tip-enhanced Raman spectroscopy to microbiology, as well as
      the move towards rapid microbial identification with Raman spectroscopy.
      Furthermore, recent studies have combined Raman spectroscopy with microfluidic
      devices, giving greater control of sample conditions, which will no doubt have an
      important impact in the future development of Raman spectroscopy for microbial
      identification.

PMID- 21958141
TI  - An unhealthy relationship: viral manipulation of the nuclear receptor
      superfamily.
AB  - The nuclear receptor (NR) superfamily is a diverse group of over 50 proteins
      whose function is to regulate the transcription of a vast array of cellular
      genes. These proteins are able to tune transcription over an extremely dynamic
      range due to the fact that they may act as either transcriptional activators or
      repressors depending on promoter context and ligand status. Due to these unique
      properties, diverse families of viruses have evolved strategies to exploit NRs in
      order to regulate expression of their own genes and to optimize the cellular
      milieu to facilitate the viral lifecycle. While the specific NRs targeted by
      these viruses vary, the strategies used to target them are common. This is
      accomplished at the cis-level by incorporation of nuclear receptor response
      elements into the viral genome and at the trans-level by viral proteins that
      target NRs directly or indirectly to modulate their function. The specific NR(s)
      targeted by a particular virus are likely to be reflective of the tissue tropism
      of the virus in question. Thus, the essential role played by NRs in the
      replication cycles of such diverse viruses underscores the importance of
      understanding their functions in the context of specific infections. This
      knowledge will allow appropriate considerations to be made when treating infected
      individuals with hormone-associated diseases and will potentially assist in the
      rational design of novel antiviral therapeutics.

PMID- 21958142
TI  - Redefining latent tuberculosis.
AB  - TB remains a public health problem worldwide, in part due to latent TB infection
      that serves as a global reservoir of potential disease. In the 20th century, the
      natural history of TB was defined by clinical symptoms, the tuberculin skin test
      and chest x-ray. The last decade witnessed the invention and application of IFN
      gamma release assays and newer immunological tools that enabled a re-appraisal of
      the natural history of TB. Here, we review the conventional understanding of
      latent TB and recount how immunology has redefined latent TB as a spectrum of
      pathogen burden and host immune control. We discuss recent and future advances in
      the fields of TB immunology and diagnostics that will improve public health
      strategies to control TB.

PMID- 21958143
TI  - Drug resistance in human African trypanosomiasis.
AB  - Human African trypanosomiasis or 'sleeping sickness' is a neglected tropical
      disease caused by the parasite Trypanosoma brucei. A decade of intense
      international cooperation has brought the incidence to fewer than 10,000 reported
      cases per annum with anti-trypanosomal drugs, particularly against stage 2
      disease where the CNS is involved, being central to control. Treatment failures
      with melarsoprol started to appear in the 1990s and their incidence has risen
      sharply in many foci. Loss of plasma membrane transporters involved in drug
      uptake, particularly the P2 aminopurine transporter and also a transporter termed
      the high affinity pentamidine transporter, relate to melarsoprol resistance
      selected in the laboratory. The same two transporters are also responsible for
      the uptake of the stage 1 drug pentamidine and, to varying extents, other
      diamidines. However, reports of treatment failures with pentamidine have been
      rare from the field. Eflornithine (difluoromethylornithine) has replaced
      melarsoprol as first-line treatment in many regions. However, a need for
      protracted and complicated drug dosing regimens slowed widespread implementation
      of eflornithine monotherapy. A combination of eflornithine with nifurtimox
      substantially decreases the required dose and duration of eflornithine
      administration and this nifurtimox-eflornithine combination therapy has enjoyed
      rapid implementation. Unfortunately, selection of resistance to eflornithine in
      the laboratory is relatively easy (through loss of an amino acid transporter
      believed to be involved in its uptake), as is selection of resistance to
      nifurtimox. The first anecdotal reports of treatment failures with eflornithine
      monotherapy are emerging from some foci. The possibility that parasites resistant
      to melarsoprol on the one hand, and eflornithine on the other, are present in the
      field indicates that genes capable of conferring drug resistance to both drugs
      are in circulation. If new drugs, that act in ways that will not render them
      susceptible to resistance mechanisms already in circulation do not appear soon,
      there is also a risk that the current downward trend in Human African
      trypanosomiasis prevalence will be reversed and, as has happened in the past, the
      disease will become resurgent, only this time in a form that resists available
      drugs.

PMID- 21958144
TI  - Whole-genomic analysis of rotavirus strains: current status and future prospects.
AB  - Studies on genetic diversity of rotaviruses have been primarily based on the
      genes encoding the antigenically significant VP7 and VP4 proteins. Since the
      rotavirus genome has 11 segments of RNA that are vulnerable to reassortment
      events, analyses of the VP7 and VP4 genes may not be sufficient to obtain
      conclusive data on the overall genetic diversity, or true origin of strains. In
      the last few years following the advent of the whole-genome-based genotype
      classification system, the whole genomes of at least 167 human group A rotavirus
      strains have been analyzed, providing a plethora of new and important information
      on the complex origin of strains, inter- and intra-genogroup reassortment events,
      animal-human reassortment events, zoonosis, and genetic linkages involving
      different group A rotavirus gene segments. In addition, the whole genomes of a
      limited number of human group B, C and novel group rotavirus strains have been
      analyzed. This article briefly reviews the available data on whole-genomic
      analysis of human rotavirus strains. The significance and future prospects of
      whole-genome-based studies are also discussed.

PMID- 21958145
TI  - Xpert(r) MTB/RIF assay: development, evaluation and implementation of a new rapid
      molecular diagnostic for tuberculosis and rifampicin resistance.
AB  - Global TB control efforts have been severely hampered by the lack of diagnostic
      tests that are accurate, simple to use and can be applied at the point of
      clinical care. This has been further compounded by the widespread inability to
      test for drug resistance. The Xpert((r)) MTB/RIF assay is a rapid molecular assay
      that can be used close to the point of care by operators with minimal technical
      expertise, enabling diagnosis of TB and simultaneous assessment of rifampicin
      resistance to be completed within 2 h. Moreover, this can be accomplished using
      unprocessed sputum samples as well as clinical specimens from extrapulmonary
      sites. We review in detail the development of this assay, its evaluation within
      the laboratory, its utility among adult and pediatric TB suspects, its use as a
      screening tool for HIV-associated TB and studies of its implementation at the
      district and sub-district levels in resource-limited settings. Following
      endorsement by the WHO in 2010, we consider the next steps in the implementation
      of the assay and its potential impact in high burden settings.

PMID- 21958147
TI  - Clinical significance and antibiotic susceptibilities of nontuberculous
      mycobacteria from patients in Crete, Greece.
AB  - AIM: To describe the clinical significance and antibiotic susceptibilities of
      nontuberculous mycobacteria (NTM) isolated from patients in Crete, Greece between
      January 2000 and December 2009. PATIENTS & METHODS: NTM identification was
      performed using conventional bacteriological methods and confirmed by molecular
      characterization with commercially available assays. Rare and novel species were
      identified by sequencing of the 16SrRNA and of the hsp65 genes. Antibiotic
      susceptibility testing was performed by E-test. Rapidly growing (RGM) and slowly
      growing (SGM) NTM were tested against 14 antimicrobials, including nine common
      ones, except for Mycobacterium avium and Mycobacterium intracellulare (MAC)
      complex isolates that were tested only against azithromycin, clarithromycin,
      linezolid and moxifloxacin. RESULTS: During the study period, 290 positive
      samples for NTM were recovered from 207 patients. Among the positive samples, 150
      were identified as SGM and 57 as RGM. Overall, 50 patients met American Thoracic
      Society criteria for disease due to NTM, 42 by SGM and eight by RGM. Risk factors
      in patients with NTM disease were underlying lung diseases, mainly chronic
      obstructive pulmonary disease and asthma, smoking, rheumatoid arthritis, AIDS,
      alcohol or drug abuse, malignancies and bronchiectasis. The most common disease
      causing species were the MAC complex (n = 25) followed by Mycobacterium kansasii
      (n = 10). Amikacin was the most active drug for RGM with 100% susceptibility.
      Macrolides were very active against isolates of the MAC complex, while
      tigecycline had excellent activity in vitro against RGM. M. kansasii was the most
      susceptible NTM species in vitro. CONCLUSION: Our study is the first to describe
      the clinical significance, risk factors and susceptibility patterns of NTM
      isolates in a Greek population.

PMID- 21958146
TI  - Human papillomavirus and cervical cancer: biomarkers for improved prevention
      efforts.
AB  - While organized screening programs in industrialized countries have significantly
      reduced cervical cancer incidence, cytology-based screening has several
      limitations. Equivocal or mildly abnormal Pap tests require costly retesting or
      diagnostic work-up by colposcopy and biopsy. In low-resource countries, it has
      been difficult to establish and sustain cytology-based programs. Advances in
      understanding human papillomavirus biology and the natural history of human
      papillomavirus-related precancers and cancers have led to the discovery of a
      range of novel biomarkers in the past decade. In this article, we will discuss
      the potential role of new biomarkers for primary screening, triage and diagnosis
      in high-resource countries and their promise for prevention efforts in resource
      constrained settings.

PMID- 21958149
TI  - Fluoroquinolone-resistant E. coli in intestinal flora of patients undergoing
      transrectal ultrasound-guided prostate biopsy--should we reassess our practices
      for antibiotic prophylaxis?
AB  - Although the estimate of the incidence of sepsis following transrectal ultrasound
      guided prostate biopsy (TRUSPB) is low, fluoroquinolone-resistant infections
      after prostate biopsy are being increasingly noted. This study was aimed at
      determining the prevalence of faecal carriage of fluoroquinolone-resistant
      Escherichia coli strains before TRUSPB and at evaluating potential predisposing
      risk factors. The incidence of sepsis after prostate biopsy was determined, and
      our routine practice for antibiotic prophylaxis for TRUSPB was evaluated. A
      prospective study was conducted in 342 consecutive patients undergoing prostate
      biopsy between December 2009 and July 2010. Before TRUSPB, a rectal swab was
      cultured. The correlation between the presence of fluoroquinolone-resistant
      strains and plausible risk factors was investigated by the use of a
      questionnaire. Of the 236 patients included, 22.0% (52/236) harboured
      ciprofloxacin-resistant E. coli strains. The use of fluoroquinolones in the 6
      months before biopsy was associated with an increased risk of faecal carriage of
      fluoroquinolone-resistant E. coli strains (p <0.01). Faecal carriage of
      fluoroquinolone-resistant E. coli strains was an important risk factor for
      infectious complications after TRUSPB (p <0.01). In conclusion, a significant
      number of patients have faecal carriage of fluoroquinolone-resistant E. coli
      strains (22.0%) before TRUSPB. The use of fluoroquinolones in the previous 6
      months before biopsy is a risk factor for faecal carriage of fluoroquinolone
      resistant E. coli strains and for infectious complications after TRUSPB. Hence,
      the universal administration of fluoroquinolones should be reconsidered.

PMID- 21958151
TI  - Short and efficient synthetic route to methyl alpha-trioxacarcinoside B and
      anomerically activated derivatives.
AB  - A 9-step synthetic route to the complex carbohydrate methyl alpha
      trioxacarcinoside B from 2-acetylfuran is described. Anomerically activated
      forms, including 1-phenylthio, 1-O-(4'-pentenyl), 1-fluoro, and 1-O-acetyl
      derivatives are also prepared.

PMID- 21958152
TI  - Postmortem changes in pork muscle protein phosphorylation in relation to the RN
      genotype.
AB  - Postmortem changes in pork muscle protein phosphorylation in relation to the RN(
      ) genotype were investigated using one-dimensional gel electrophoresis and a
      phosphor specific staining. The phosphorylation levels of several protein bands
      were found to be affected by the RN(-) genotype and to change during postmortem
      development. Glycogen phosphorylase, phosphofructokinase, and pyruvate kinase
      were found in protein bands affected by the RN(-) genotype, and the
      phosphorylation profile indicates that part of the increased rate and extended pH
      decline of the RN(-) genotype could be a consequence of phosphorylation of these
      key enzymes during the postmortem metabolism. The results illustrate that the
      protein phosphorylation level of the muscle proteins could be interpreted as a
      global metabolic fingerprint containing information about the activity status of
      the enzymes in the postmortem metabolism.

PMID- 21958150
TI  - Titanocene-phosphine derivatives as precursors to cytotoxic heterometallic TiAu2
      and TiM (M = Pd, Pt) compounds. Studies of their interactions with DNA.
AB  - A series of tri- and bimetallic titanium-gold, titanium-palladium, and titanium
      platinum derivatives of the general formulas [Ti{eta(5)
      C(5)H(4)(CH(2))(n)PPh(2)(AuCl)}(2)].2THF [n = 0 (1); n = 2 (2); n = 3 (3)] and
      [TiCl(2){eta(5)-C(5)H(4)kappa-(CH(2))(n)PPh(2)}(2)(MCl(2))].2THF [M = Pd, n = 0
      (4); n = 2 (5); n = 3 (6) ; M = Pt, n = 0 (7); n = 2 (8); n = 3 (9)] have been
      synthesized and characterized by different spectroscopic techniques and mass
      spectrometry. The molecular structures of compounds 1-9 have been investigated by
      means of density functional theory calculations. The calculated IR spectra of the
      optimized structures fit well with the experimental IR data obtained for 1-9. The
      stability of the heterometallic compounds in deuterated solvents [CDCl(3),
      dimethyl sulfoxide (DMSO)-d(6), and mixtures 50:50 DMSO-d(6)/D(2)O and 1:99 DMSO
      d(6)/D(2)O at acidic and neutral pH] has been evaluated by (31)P and (1)H NMR
      spectroscopy showing a higher stability for these compounds than for Cp(2)TiCl(2)
      or precursors [Ti{eta(5)-C(5)H(4)(CH(2))(n)PPh(2)}(2)]. The new compounds display
      a lower acidity (1-2 units) than Cp(2)TiCl(2). The decomposition products have
      been identified over time. Complexes 1-9 have been tested as potential anticancer
      agents, and their cytotoxicity properties were evaluated in vitro against HeLa
      human cervical carcinoma and DU-145 human prostate cancer cells. TiAu(2) and TiPd
      compounds were highly cytotoxic for these two cell lines. The interactions of the
      compounds with calf thymus DNA have been evaluated by thermal denaturation (1-9)
      and by circular dichroism (1, 3, 4, and 7) spectroscopic methods. All of these
      complexes show a stronger interaction with DNA than that displayed by
      Cp(2)TiCl(2) at neutral pH. The data are consistent with electrostatic
      interactions with DNA for TiAu(2) compounds and for a covalent binding mode for
      TiM (M = Pd, Pt) complexes.

PMID- 21958153
TI  - The burden of diabetes mortality in Finland 1988-2007 - a brief report.
AB  - BACKGROUND: Increasing incidence of diabetes has been reported in many countries
      and the disease burden related to diabetes to be distributed unevenly across the
      population. Patients with lower socioeconomic position have been reported to have
      higher diabetes prevalence, higher rates of diabetes related complications and
      excess mortality. This study examined trends in gender, age and socioeconomic
      differences in the burden of diabetes mortality in the Finnish population aged 35
      80 and potential years of life lost (PYLL) due to diabetes. METHODS: The data
      consist of an 11% random sample of Finnish residents in 1987-2007 and an 80%
      oversample of persons who died during those years. We examined diabetes both as
      underlying and contributory cause. We calculated age-specific and age
      standardized diabetes death rates by gender and socioeconomic position using the
      direct method and PYLL due to diabetes related deaths for 2004-2007. RESULTS:
      Diabetes related mortality was higher among older Finns. A clear and systematic
      socioeconomic pattern was detected among both men and women: the higher the
      socioeconomic position the lower the mortality. The contribution of diabetes to
      PYLL was 8% among men and 6% among women. Among women, the contribution of
      diabetes to PYLL was lower in higher socioeconomic groups, whereas among men, the
      contribution was similar in all socioeconomic groups. CONCLUSIONS: In order to
      further reduce the burden of diabetes a better treatment balance to prevent
      diabetes complications would significantly decrease the burden of diabetes
      mortality. Use of underlying and contributory causes of death is useful in
      monitoring trends and sub-group differences in the burden of diabetes.

PMID- 21958155
TI  - Are reductions in industrial organic contaminants emissions in rich countries
      achieved partly by export of toxic wastes?
AB  - Recent studies show that PCB (polychlorinated biphenyl) air concentrations remain
      surprisingly high in parts of Africa and Asia. These are regions where PCBs were
      never extensively used, but which are implicated as recipients of obsolete
      products and wastes containing PCBs and other industrial organic contaminants,
      such as halogenated flame retardants (HFRs). We hypothesize that there may be
      different trends in emissions across the globe, whereby emissions of some
      industrial organic contaminants may be decreasing faster in former use regions
      (due to emission reductions combined with uncontrolled export), at the expense of
      regions receiving these substances as obsolete products and wastes. We conclude
      that the potential for detrimental effects on the environment and human health
      due to long-range transport by air, water, or wastes should be of equal concern
      when managing and regulating industrial organic contaminants. This calls for a
      better integration of life-cycle approaches in the management and regulation of
      industrial organic contaminants in order to protect environmental and human
      health on a global scale. Yet, little remains known about the amounts of
      industrial organic contaminants exported outside former use regions as different
      types of wastes because of the often illicit nature of these operations.

PMID- 21958154
TI  - Genome-wide examination of the transcriptional response to ecdysteroids 20
      hydroxyecdysone and ponasterone A in Drosophila melanogaster.
AB  - BACKGROUND: The 20-hydroxyecdysone (20E) hierarchy of gene activation serves as
      an attractive model system for studying the mode of steroid hormone regulated
      gene expression and development. Many structural analogs of 20E exist in nature
      and among them the plant-derived ponasterone A (PoA) is the most potent. PoA has
      a higher affinity for the 20E nuclear receptor, composed of the ecysone receptor
      (EcR) and Ultraspiracle proteins, than 20E and a comparison of the genes
      regulated by these hormones has not been performed. Furthermore, in Drosophila
      different cell types elicit different morphological responses to 20E yet the cell
      type specificity of the 20E transcriptional response has not been examined on a
      genome-wide scale. We aim to characterize the transcriptional response to 20E and
      PoA in Drosophila Kc cells and to 20E in salivary glands and provide a robust
      comparison of genes involved in each response. RESULTS: Our genome-wide
      microarray analysis of Kc167 cells treated with 20E or PoA revealed that far more
      genes are regulated by PoA than by 20E (256 vs 148 respectively) and that there
      is very little overlap between the transcriptional responses to each hormone.
      Interestingly, genes induced by 20E relative to PoA are enriched in functions
      related to development. We also find that many genes regulated by 20E in Kc167
      cells are not regulated by 20E in salivary glands of wandering 3rd instar larvae
      and we show that 20E-induced levels of EcR isoforms EcR-RA, ER-RC, and EcR-RD/E
      differ between Kc cells and salivary glands suggesting a possible cause for the
      observed differences in 20E-regulated gene transcription between the two cell
      types. CONCLUSIONS: We report significant differences in the transcriptional
      responses of 20E and PoA, two steroid hormones that differ by only a single
      hydroxyl group. We also provide evidence that suggests that PoA induced death of
      non-adapted insects may be related to PoA regulating different set of genes when
      compared to 20E. In addition, we reveal large differences between Kc cells and
      salivary glands with regard to their genome-wide transcriptional response to 20E
      and show that the level of induction of certain EcR isoforms differ between Kc
      cells and salivary glands. We hypothesize that the differences in the
      transcriptional response may in part be due to differences in the EcR isoforms
      present in different cell types.

PMID- 21958156
TI  - Alveolar mast cells shift to an FcepsilonRI-expressing phenotype in mild atopic
      asthma: a novel feature in allergic asthma pathology.
AB  - BACKGROUND: A unique feature of alveolar mast cells is their low high-affinity
      IgE receptor (FcepsilonRI) expression. Recent discoveries in uncontrolled asthma
      suggest that the appearance of FcepsilonRI-expressing alveolar mast cells may be
      a novel disease-specific feature of allergic asthma. This study investigates
      whether increased FcepsilonRI-expressing alveolar mast cells are present in
      patients with mild allergic asthma or even in non-asthmatic allergic rhinitis
      patients (AR) who have developed bronchial hyperactivity (BHR). METHODS:
      Bronchial and alveolar tissues were obtained from healthy controls, AR patients
      with or without BHR, and AR patients with concurrent asthma. Samples were
      processed for immunohistochemical identification of MC(T) and MC(TC) and
      expression of FcepsilonRI and surface-bound IgE. RESULTS: Bronchial mast cell
      expression of FcepsilonRI was high in all groups. In contrast, in the alveolar
      tissue, the expression of FcepsilonRI on mast cells was low in healthy controls
      and in the AR patient groups, whereas a high expression was present in AR
      patients with concurrent asthma (P = 0.006 compared to controls). The asthmatics
      had a 29-fold increase in numbers (P = 0.006) and a 19-fold increase in
      proportion (P = 0.007) of alveolar mast cells that expressed surface-bound IgE.
      CONCLUSIONS: The present data show that alveolar mast cells in patients with mild
      atopic asthma, but not atopic patients with AR, have turned into a highly
      FcepsilonRI- and IgE-expressing phenotype. These data support the hypothesis that
      increased FcepsilonRI expression on alveolar mast cells is a novel disease
      specific feature of allergic asthma that is important for understanding asthma
      phenotypes and designing new therapeutic strategies.

PMID- 21958157
TI  - Copper-mediated C-H activation/C-S cross-coupling of heterocycles with thiols.
AB  - We report the synthesis of a series of aryl- or alkyl-substituted 2
      mercaptobenzothiazoles by direct thiolation of benzothiazoles with aryl or alkyl
      thiols via copper-mediated aerobic C-H bond activation in the presence of
      stoichiometric CuI, 2,2'-bipyridine and Na(2)CO(3). We also show that the
      approach can be extended to thiazole, benzimidazole, and indole substrates. In
      addition, we present detailed mechanistic investigations on the Cu(I)-mediated
      direct thiolation reactions. Both computational studies and experimental results
      reveal that the copper-thiolate complex [(L)Cu(SR)] (L: nitrogen-based bidentate
      ligand such as 2,2'-bipyridine; R: aryl or alkyl group) is the first reactive
      intermediate responsible for the observed organic transformation. Furthermore,
      our computational studies suggest a stepwise reaction mechanism based on a
      hydrogen atom abstraction pathway, which is more energetically feasible than many
      other possible pathways including beta-hydride elimination, single electron
      transfer, hydrogen atom transfer, oxidative addition/reductive elimination, and
      sigma-bond metathesis.

PMID- 21958158
TI  - Development and in vitro characterization of a novel bifunctional MU
      agonist/delta-antagonist opioid tetrapeptide.
AB  - The development of tolerance to and dependence on opioid analgesics greatly
      reduces their long-term usefulness. Previous studies have demonstrated that co
      administration of a MU-opioid receptor (MOR) agonist and delta-opioid receptor
      (DOR) antagonist can decrease MOR agonist-induced tolerance and dependence
      development after chronic exposure. Clinically, a single ligand displaying
      multiple efficacies (e.g., MOR agonism concurrently with DOR antagonism) would be
      of increased value over two drugs administered simultaneously. Guided by modeling
      of receptor-ligand complexes we have developed a series of potent non-selective
      opioid tetrapeptides that have differing efficacy at MOR and DOR. In particular,
      our lead peptide (KSK-103) binds with equal affinity to MOR and DOR but acts as a
      MOR agonist with similar efficacy but greater potency than morphine and a DOR
      antagonist in cellular assays measuring both G protein stimulation and adenylyl
      cyclase inhibition.

PMID- 21958159
TI  - Enzymatic methyl transfer: role of an active site residue in generating active
      site compaction that correlates with catalytic efficiency.
AB  - Human catechol-O-methyltransferase (COMT) catalyzes a methyl transfer from S
      adenosylmethionine (AdoMet) to dopamine. Site-specific mutants at three positions
      (Tyr68, Trp38, and Val108) have been characterized with regard to product
      distribution, catalytic efficiency, and secondary kinetic isotope effects. The
      series of mutations at Tyr68 within wild-type protein and the common polymorphic
      variant (Val108Met) yields a linear correlation between the catalytic efficiency
      and the size of the secondary kinetic isotope effect. We conclude that active
      site compaction in COMT is modulated by a proximal side chain residing behind the
      sulfur-bearing methyl group of AdoMet. These findings are discussed in the
      context of the active site compression that has been postulated to accompany
      enzyme-supported hydrogen tunneling.

PMID- 21958160
TI  - Novel naphthalimide-benzoic acid conjugates as potential apoptosis-inducing
      agents: design, synthesis, and biological activity.
AB  - A series of novel naphthalimide derivatives with 4-[4-(3,3
      diphenylallyl)piperazin-1-yl]benzoic acid as side chain were designed and
      synthesized. Their antitumor activities were evaluated against a variety of
      cancer cell lines in vitro. Preliminary results showed that most of the
      derivatives had cytotoxic activity comparable with that of amonafide, with IC50
      values of 10-6-10-5 M. Interestingly, compound 12e had the unique antitumor
      activity against MCF-7 among the cancer cell lines tested. More importantly, flow
      cytometric analysis indicated that compared with amonafide, the target compounds
      could effectively induce G2/M arrest and progress to apoptosis in HL-60 cells
      after double staining with annexin V-FITC and propidium iodide. The present work
      provided a novel class of naphthalimide-based derivatives with potential
      apoptosis-inducing and improved antitumor activity for further optimization.

PMID- 21958161
TI  - Research for food and health in Europe: themes, needs and proposals.
AB  - BACKGROUND: Diet, in addition to tobacco, alcohol and physical exercise, is a
      major factor contributing to chronic diseases in Europe. There is a pressing need
      for multidisciplinary research to promote healthier food choices and better
      diets. Food and Health Research in Europe (FAHRE) is a collaborative project
      commissioned by the European Union. Among its tasks is the description of
      national research systems for food and health and, in work reported here, the
      identification of strengths and gaps in the European research base. METHODS: A
      typology of nine research themes was developed, spanning food, society, health
      and research structures. Experts were selected through the FAHRE partners, with
      balance for individual characteristics, and reported using a standardised
      template. RESULTS: Countries usually commission research on food, and on health,
      separately: few countries have combined research strategies or programmes. Food
      and health are also strongly independent fields within the European Commission's
      research programmes. Research programmes have supported food and bio-technology,
      food safety, epidemiological research, and nutritional surveillance; but there
      has been less research into personal behaviour and very little on environmental
      influences on food choices - in the retail and marketing industries, policy, and
      regulation. The research is mainly sited within universities and research
      institutes: there is relatively little published research contribution from
      industry. DISCUSSION: National food policies, based on epidemiological evidence
      and endorsed by the World Health Organisation, recommend major changes in food
      intake to meet the challenge of chronic diseases. Biomedical and biotechnology
      research, in areas such as 'nutrio-genomics', 'individualised' diets,
      'functional' foods and 'nutri-pharmaceuticals' appear likely to yield less health
      benefit, and less return on public investment, than research on population-level
      interventions to influence dietary patterns: for example policies to reduce
      population consumption of trans fats, saturated fats, salt and energy density.
      Research should now address how macro-diets, rather than micro-nutritional
      content, can be improved for beneficial impacts on health, and should evaluate
      the impact of market changes and policy interventions, including regulation, to
      improve public health. CONCLUSIONS: European and national research on food and
      health should have social as well as commercial benefits. Strategies and policies
      should be developed between ministries of health and national research funding
      agencies. Collaboration between member states in the European Union can yield
      better innovation and greater competitive advantage.

PMID- 21958163
TI  - Role of the PI3K-TOR-S6K pathway in the onset of cell cycle elongation during
      Xenopus early embryogenesis.
AB  - In the early embryogenesis of the frog, Xenopus laevis, cells proliferate by
      rapid and synchronous divisions, followed by cell cycle elongation and
      prolongation of the S phases, and then the appearance of the G2 and G1 phases
      after the midblastula transition (MBT). The beginning of cell cycle elongation
      was thought to depend on an increase in the nucleo-cytoplasmic (N/C) ratio in
      blastomeres and a decrease in cortical cytoplasmic factors necessary for cell
      cycle progression, although these factors are unknown. In the present study, we
      demonstrated that a regulatory subunit of PI3K (p85alpha) was localized in the
      cortical cytoplasm of the blastomere during the MBT. When the embryos were
      treated with a PI3K inhibitor, LY294002, or a TOR inhibitor, rapamycin, cell
      cycle elongation was initiated before the MBT. In addition, the inhibition of S6K
      expression by antisense morpholino oligo enhanced the initiation of cell cycle
      elongation. In contrast, the activation of PI3K-TOR by Rheb-S16H expression
      delayed the initiation of cell cycle elongation. These results indicate that a
      decrease in translational activity dependent on the PI3K-TOR-S6K pathway causes
      the initiation of cell cycle elongation at the onset of the MBT.

PMID- 21958167
TI  - General description of the adsorption of proteins at their iso-electric point in
      nanoporous materials.
AB  - A simple but remarkably precise geometric pore-filling model is proposed and
      experimentally validated for the adsorption of proteins at their iso-electric
      point (pI) in nanoporous materials. Three different globular proteins-lysozyme,
      myoglobin, and bovine serum albumin-are used as model proteins to study protein
      adsorption on two types of ordered mesoporous materials-silica and carbon-which
      allows us to study the effects of protein and surface structure on the protein
      adsorption mechanism. The geometric pore-filling model confirms that proteins are
      closely packed inside the pore channels of mesoporous materials, leading to an
      exceptionally large protein loading capacity. A relationship for the amount of
      adsorbed protein as a function of protein size, nanopore volume, and pore
      diameter is derived. The pore space gradually fills up to complete packing of the
      available pore space at the highest protein concentration. The high precision of
      the geometric pore-filling model demonstrates its utility to predict the protein
      adsorption capacity of ordered nanoporous materials.

PMID- 21958168
TI  - RNA and DNA complexes with hemin [Fe(III) heme] are efficient peroxidases and
      peroxygenases: how do they do it and what does it mean?
AB  - Guanine-rich RNAs and DNAs from chromosomal telomeres and elsewhere that fold
      into guanine quadruplexes (G-quadruplexes), are found to complex tightly with
      porphyrins such as N-methylmesoporphyrin IX (NMM) and hemin [Fe(III) heme]. By
      themselves, these DNAs and RNAs are found to be efficient catalysts for porphyrin
      metallation. When complexed with hemin, under physiological conditions, these
      nucleic acids display robust peroxidase (one-electron oxidation), as well as
      peroxygenase (two-electron oxidation, or oxygen transfer) activity. These
      surprising catalytic properties, that frequently match the catalytic performance
      of natural peroxidase and P450 monooxygenase enzymes, have been the subject of
      significant mechanistic analysis, as well as having found utility in a wide range
      of biosensing and other applications. This review summarizes recent insights into
      a surprising yet fundamental property of many RNAs and DNAs, a property with
      undoubted ramifications for cellular oxidative disease, de novo hemoenzyme
      design, and our understanding of the evolution of early biocatalytic systems.

PMID- 21958169
TI  - Inflammatory corneal neovascularization: etiopathogenesis.
AB  - There is a delicate balance between pro-angiogenic stimuli and anti-angiogenic
      stimuli in the normal cornea. This balance allows the cornea to normally exist in
      a relatively avascular state, which is needed for optical clarity and vision.
      However, in the setting of inflammation, this balance may be shifted in favor of
      neovascularization.   This paper reviews the literature on corneal inflammatory
      neovascularization beginning with the pro-angiogenic factors, such as Vascular
      Endothelial Growth Factor and Fibroblast Growth Factor, which help to facilitate
      the development of new corneal vessels. Subsequently the anti-angiogenic factors
      and their role in preventing neovascularization in the normal cornea are
      reviewed. Finally, a review of several etiologies of inflammatory
      neovascularization is presented with attention to the processes that allow the
      pro-angiogenic stimuli to overwhelm the anti-angiogenic factors.

PMID- 21958170
TI  - Delayed type hypersensitivity in the pathogenesis of recurrent herpes stromal
      keratitis.
AB  - Recurrent herpes stromal keratitis (HSK) is one of the leading causes of
      blindness in the developed world. Cyokines characteristic of Th1 cells (in
      particular IFN-gamma and IL-2) have been shown to dominate in HSK in addition to
      mechanisms by nonspecific, antigen-independent effector cells such as
      neutrophils, basophils, and monocytes. More recently, the migration and
      maturation of dendritic cells (DC) within the corneal stroma of patients with HSK
      have been recognized as contributors to recurrent disease, suggesting a role for
      delayed type hypersensitivity (DTH) in the immunopathogenesis of HSK. The role of
      DC and DTH in recurrent HSK has not been studied extensively and experimental
      models of recurrent HSK focusing on DTH as the pathogenesis and viral particles
      as the triggering antigen may contribute to better understanding of the disease.

PMID- 21958171
TI  - Keratoconjunctivitis sicca manifestations in ocular graft versus host disease:
      pathogenesis, presentation, prevention, and treatment.

PMID- 21958172
TI  - Relapsing polychondritis: systemic and ocular manifestations, differential
      diagnosis, management, and prognosis.
AB  - Relapsing polychondritis (RP) is a rare systemic autoimmune disease characterized
      by episodic inflammation of cartilaginous tissues throughout the body. It is
      distinguished by recurrent bouts of inflammation, which lead to the permanent
      destruction of the involved structures. It can be a life-threatening,
      debilitating, and frightening disease and is often difficult to diagnose in its
      early stages. Ocular manifestations have been reported to occur in up to 65% of
      cases and include proptosis, eyelid edema, extraocular muscles palsy,
      episcleritis, scleritis, conjunctivitis, corneal infiltrate, peripheral
      ulcerative keratitis, corneal thinning or perforation, iridocyclitis, cataract,
      retinopathy, exudative retinal detachment, and optic neuritis. Corticosteroids
      remain the mainstay of treatment for RP; however, other treatment modalities
      include nonsteroidal anti-inflammatory drugs, colchicine, dapsone, and
      immunomodulatory drugs. This article reviews the literature and summarizes the
      epidemiology, pathogenesis, clinical features, treatment, and prognosis of the
      systemic and ocular manifestations of RP.

PMID- 21958173
TI  - Ocular cicatricial pemphigoid: a review of clinical features, immunopathology,
      differential diagnosis, and current management.
AB  - Ocular cicatricial pemphigoid is a devastating autoimmune blistering disorder
      mainly affecting the conjunctiva but frequently associated with systemic mucosal
      findings. This article is an update of the pathogenesis, ocular findings,
      differential diagnosis, and approaches to treatment.

PMID- 21958174
TI  - Autoimmune basis of glaucoma.
AB  - Glaucoma is one of the leading causes of blindness worldwide. The current view of
      glaucoma is that it is a multifactorial disease. Elevated IOP is a recognized
      etiologic factor which can trigger initial damage through biomechanical and
      ischemic injury to the retinal ganglion cells. However, elevated intraocular
      pressure cannot be entirely responsible for the development of glaucoma.
      Accumulating evidence suggests that abnormal immunity may be contributing to the
      glaucomatous optic neuropathy. Autoimmunity may be responsible for initiating or
      exacerbating glaucoma. This review provides an evaluation of the potential role
      of autoimmunity in some patients with glaucoma.

PMID- 21958176
TI  - The use of prostaglandin analogs in the uveitic patient.
AB  - Glaucoma is a disease process characterized by progressive optic nerve damage and
      corresponding visual field loss. It may be further categorized into either
      primary open-angle glaucoma or secondary glaucoma. These secondary glaucomas
      include glaucomas associated with uveitis and inflammation. Prostaglandin analogs
      (PGA) have been used to help lower intraocular pressure (IOP) in these often
      difficult to manage eyes. However, controversy exists concerning their use in
      uveitic patients due to the theoretically higher risk of anterior uveitis,
      development of cystoid macular edema (CME), and reactivation of herpes simplex
      keratitis (HSK). There is little evidence that PGA disrupt the blood-aqueous
      barrier and only anecdotal evidence suggesting an increased risk of these rare
      findings. PGA may be used in uveitic glaucoma when other topical treatments have
      not lowered IOP to the patient's target range.

PMID- 21958175
TI  - Posner-Schlossman glaucomatocyclitic crisis.
AB  - In 1948, Posner and Schlossman first reported glaucomatocyclitic crisis, an
      uncommon form of glaucoma characterized by recurrent unilateral episodes of
      markedly elevated intraocular pressure (IOP) with mild idiopathic anterior
      chamber inflammation. The exact etiology of glaucomatocyclitic crisis is not
      clear. Although it is typically a self-limited condition, some cases with
      advanced optic nerve cupping and associated visual field loss have been reported.
      Diagnosis of Posner-Schlossman syndrome is difficult, and it may mimic a variety
      of ocular disorders. Treatment of this syndrome is directed towards controlling
      the inflammation and associated IOP elevation.

PMID- 21958177
TI  - Delayed sterile endophthalmitis after glaucoma drainage implantation.
AB  - Glaucoma drainage devices are being used with increasing frequency for patients.
      Sterile endophthalmitis after implantation has been reported. Unlike traditional
      trabeculectomy surgery, the persistence of an implant may be contributory. As
      glaucoma specialists consider emerging technologies in implantable glaucoma
      drainage devices, it is important to understand that sterile endophthalmitis may
      be associated with these devices.

PMID- 21958178
TI  - The use of biologic agents in the treatment of ocular manifestations of Behcet's
      disease.
AB  - Behcet's Disease (BD) is a multisystem inflammatory disorder of uncertain
      etiology with a variety of potential manifestations throughout the body, and its
      ocular complications are some of its most devastating. Treatment with
      immunosuppressive agents has improved outcomes, but many patients suffer from
      disease that responds poorly to conventional therapies. Because of this, therapy
      with a variety of biological response modifiers has been employed. The earliest
      was interferon-alpha, and a multitude of reports have described its benefits for
      the uveitis associated with Behcet's Disease. Many patients enjoy durable
      remissions of their ocular inflammatory disease even after discontinuation of
      therapy, but side-effects are almost universal and some can be dangerous. Of the
      newer biological response modifiers, infliximab, a monoclonal antibody to TNF
      alpha, has been most extensively studied. It is reported to be rapidly effective
      in many cases of Behcet's Disease uveitis, though with conflicting data as to the
      ability to induce durable remission after cessation of treatment. Side-effects
      are relatively rare, but may be serious. Several reports have been published on
      the use of other biologic agents, including adalimumab (a humanized antibody to
      TNF-alpha), etanercept (a molecule that resembles the TNF-alpha receptor), and
      rituximab (an antibody to CD20 that depletes the body of CD20-positive B cells).
      Of the three of these, adalimumab has the most promising initial evidence,
      etanercept has very few positive reports in patients with BD uveitis (and is
      likely ineffective in uveitis in general), and rituximab is lacking data.
      Although randomized controlled trials are almost completely lacking, currently
      available evidence is promising that biologic agents can prove an invaluable
      addition to the armamentarium of the practitioner treating patients with BD
      uveitis.

PMID- 21958179
TI  - Autoimmunity and age-related macular degeneration: a review of the literature.

PMID- 21958180
TI  - Vogt-Koyanagi-Harada syndrome: review of clinical features.
AB  - Vogt-Koyanagi-Harada syndrome is a bilateral, chronic, diffuse granulomatous
      panuveitis associated with poliosis, vitiligo, and central nervous system and
      auditory signs. Increasing reports have been published to describe the clinical
      features of Vogt-Koyanagi-Harada syndrome. These manifestations are variable.
      This article presents a review of the clinical features.

PMID- 21958181
TI  - Sympathetic ophthalmia.
AB  - Sympathetic ophthalmia is a rare, bilateral granulomatous panuveitis following
      accidental or surgical trauma to one eye. The pathophysiology is not clearly
      understood, but is believed to be a T-cell mediated autoimmune response. Clinical
      presentation most often occurs within the first year after trauma; anteriorly it
      manifests as a chronic or acute uveitis with mutton-fat keratic precipitates,
      while posteriorly it is often accompanied by yellowish-white choroidal lesions or
      Dalen-Fuchs nodules. The mainstay of treatment consists of systemic anti
      inflammatory agents such as oral corticosteroids, or other immunosuppressive
      agents. Newer treatments include intravitreal injections of steroids in
      combination with systemic therapy, periocular injections of steroids without
      systemic therapy, and injections of infliximab, an anti-vascular endothelial
      growth factor.

PMID- 21958183
TI  - Diagnostic testing and disease monitoring in birdshot chorioretinopathy.
AB  - Birdshot chorioretinopathy (BSCR) is a rare form of posterior uveitis in which
      hypopigmented choroidal lesions are scattered throughout the posterior pole. In
      order to avoid the poor natural history of BSCR, many practitioners would argue
      that it is critical to diagnose and carefully monitor the often subtle activity
      of this disease; BSCR can progress insidiously in a white and painless eye, and
      treatment algorithms based on visual acuity, vitreous inflammation, and retinal
      vascular leakage of fluorescein alone have been ineffective. This article reviews
      the various modalities that can be used to diagnose and monitor BSCR, including
      the clinical and ophthalmoscopic features, diagnostic criteria,
      electroretinography (ERG--full field, multifocal, and pattern), fluorescein
      angiography (FA), indocyanine green (ICG) angiography, optical coherence
      tomography (OCT), fundus autofluorescence (AF), visual fields, HLA A29 testing,
      and other laboratory testing. HLA-A29 testing can be useful in diagnostically
      borderline cases, but a positive test is not as useful as one might think in
      cases where the clinical suspicion for BSCR is low. Out of all the testing
      modalities, the ERG has been studied most extensively in its relationship to
      successful treatment. The key parameter is the 30 Hz flicker implicit time, which
      is abnormal in 70% of patients at baseline. A normal implicit time is correlated
      with the chance that a patient can be successfully tapered from systemic
      immunomodulatory therapy without recurrence. Alternatively, some practitioners
      use ICG angiography or visual field testing for adjunctive monitoring. OCT is
      used most commonly to follow macular edema. While there is no consensus on how to
      best monitor disease activity, our institution uses serial ERGs as an adjunct to
      the normal exam.

PMID- 21958182
TI  - Cancer-associated retinopathy: update on pathogenesis and therapy.
AB  - Paraneoplastic retinopathies comprise a diverse group of immune-mediated
      conditions affecting the eye. Cancer-associated retinopathy (CAR) typically has a
      sudden onset of severe visual loss and an ominous association with an occult
      malignancy. CAR is one of the best studied and better understood conditions in
      the multifarious group of autoimmune retinopathies. Recent developments have
      correlated the disease presentation, course, and therapeutic response to the
      underlying immune mediators and the inciting antigens. Signaling involving
      cytotoxic T-lymphocytes antigen 4 (CTLA-4) and vascular endothelial growth factor
      (VEGF) receptor-1 appears to play a role in the pathogenesis and may offer novel
      avenues for therapeutic intervention in CAR. Future developments in rapid
      identification and longitudinal quantification of antibody levels would enable
      individualized management in these patients. The goal of this review is to
      analyze the clinical features of diagnosis and management of retinopathy in the
      context of recent advances in the elucidation of CAR pathogenesis.

PMID- 21958184
TI  - Neuromyelitis optica: a review.

PMID- 21958185
TI  - Subtleties in the histopathology of giant cell arteritis.
AB  - A temporal artery biopsy is typically obtained in cases of suspected giant cell
      arteritis (GCA). The differentiation between a "positive" versus a "negative"
      biopsy is sometimes not simple. Degrees of inflammation can vary from obvious,
      florid accumulations of giant cells to subtle pockets of non-granulomatous
      inflammation. Areas of normal pathology, or "skip lesions," may be interspersed
      within inflamed sections of the artery, resulting in a false negative diagnosis.
      Other features of the biopsy, such as the state of the internal elastic lamina
      and inflammation of the adjacent, smaller vessels, must also be evaluated and
      considered as possible signs of disease. Finally, some biopsies have an
      intermediate histopathologic appearance with mild inflammation and scarring,
      which may indicate prior treatment with corticosteroids, or "healed" arteritis.
      Careful examination and clinical correlation is therefore essential to evaluate
      for these subtleties, which can affect the final diagnosis.

PMID- 21958186
TI  - Wegener's granulomatosis of the orbit: a review of clinical features and updates
      in diagnosis and treatment.
AB  - Wegener's Granulomatosis (WG) is an uncommon systemic vasculitic disease
      involving the respiratory system and kidneys. It is the most common
      antineutrophil cytoplasm antibody (ANCA)-associated vasculitis. Orbital
      involvement in WG is a rare but potentially devastating disorder leading to
      visual loss and deformity. Most clinical characteristics of this disease are non
      specific, making clinical diagnosis nearly impossible. We reviewed the features
      of WG involving the orbit including radiologic, serologic, and histopathologic
      findings. Advances in treatment are likewise discussed.

PMID- 21958187
TI  - Vascular reconstruction in monolateral dual kidney transplantation with multiple
      arteries.
AB  - We report the results of monolateral dual kidney transplantation with grafts with
      multiple arteries. Among the 42 monolateral DKT performed in a seven-yr period,
      12 (28.5%) patients received renal grafts with multiple arteries. In six
      patients, the accessory arteries were anastomosed end-to-side or side-to-side on
      the aortic patch. In six patients, with three or more accessory arteries, a
      vascular reconstruction with an inferior vena cava patch was performed, before
      implanting the kidney. There were no intraoperative complications in the entire
      series, and there were no immediate vascular complications. Vascular
      reconstruction of kidneys with multiple arteries may be performed safely even in
      monolateral dual kidney transplantation. Inferior vena cava may be an attractive
      alternative in vascular reconstruction for kidneys with multiple arteries.

PMID- 21958188
TI  - Functional analysis of the integration host factor site of the sigma(54) Pu
      promoter of Pseudomonas putida by in vivo UV imprinting.
AB  - The integration host factor (IHF) of Pseudomonas putida connects cell growth to
      transcriptional activity of distinct promoters. The IHF site of the sigma(54)
      promoter Pu of the TOL (m-xylene biodegradation) plasmid pWW0 of P. putida has
      been examined to define experimentally a relationship between occupation of the
      promoter by this factor, the biological activity of the protein and the tolerance
      of the target site to single-base changes through the bound DNA core sequence.
      The use of an in vivo high-intensity UV imprinting procedure to examine such an
      occupation of Pu by IHF allowed inspection of the interplay between the factor
      and cognate site variants under the physiologically relevant conditions of
      monocopy gene dosage. The resulting data were merged in a structural model for
      establishing key features of the IHF-DNA interaction. A functional consensus for
      first-order IHF binding was instrumental for a genome-wide survey of sequences
      with potential regulatory value. This search revealed that very few, if any, of
      the maximum 330 sites within intergenic regions were placed in locations
      controlling expression of central metabolic genes. It thus seems that the IHF
      regulon of P. putida has a degree of functional specialization that is not evenly
      distributed through all gene categories.

PMID- 21958190
TI  - Platelet function monitoring in patients on clopidogrel: What should we learn
      from GRAVITAS?
AB  - Combined inhibition of platelet aggregation is essential to prevent recurrent
      ischemic episodes in patients with acute coronary syndromes and after
      percutaneous coronary interventions (PCIs). In combination with aspirin, the ADP
      receptor antagonist clopidogrel is used widespread for this purpose; however,
      platelet reactivity after clopidogrel differs substantially between patients and
      high on-treatment platelet reactivity (HTPR) persists in a substantial proportion
      of cases. Since more than 20 prior observational studies linked HTPR to higher
      risk of ischemic events, including cardiovascular death, myocardial infarction,
      and stent thrombosis, monitoring post-clopidogrel platelet reactivity after PCI
      might be beneficial for risk assessment and to tailor the antiplatelet therapy to
      the patients' needs. However, there is no consensus on the role of routine
      platelet function monitoring in clinical guidelines. This article aims to review
      the available evidence regarding the clinical relevance of platelet function
      monitoring, highlighting possible reasons for the controversy between guidelines
      and observational studies.

PMID- 21958189
TI  - Active Toll-like receptor-7 triggering of chronic lymphocytic leukemia B-cells by
      imiquimod.

PMID- 21958191
TI  - Immune thrombocytopenia with antiphospholipid antibodies in monozygotic twins.
AB  - We describe monozygotic twins with immune thrombocytopenia (ITP) associated to
      antiphospholipid antibodies with a dissimilar clinical expression. The first
      patient was diagnosed to have ITP at 63 years old and was treated with
      corticosteroids. She presented ulterior exacerbations of thrombocytopenia
      requiring intravenous immunoglobulin and subsequent treatment with rituximab. She
      ultimately had a favorable response without thrombotic events during follow-up.
      The second patient who had a history of three spontaneous abortions and
      endometrial adenocarcinoma in complete remission was evaluated for severe
      thrombocytopenia, ITP was diagnosed at the age of 63. She was treated with
      steroids and had a favorable response. After few months she developed deep venous
      thrombosis and pulmonary embolism requiring anticoagulation therapy without
      hemorrhagic events. Both patients were found to have antiphospholipid antibodies
      and HLA DR4 (DRB1*04) and HLA DR5 (DRB1*12). The association of those two
      entities in monozygotic twins could support the presence of common predisposing
      genes. However, with both patients being genotipically identical, the clinical
      expression was different. Those cases highlight the possibility that
      environmental factors may affect the expression of those disorders.

PMID- 21958192
TI  - Real-time probing of structural dynamics by interaction between chromophores.
AB  - We present an investigation of structural dynamics in excited-state cations
      probed in real-time by femtosecond time-resolved ion photofragmentation
      spectroscopy. From photoelectron spectroscopy data on 1,3-dibromopropane we
      conclude that the pump pulse ionizes the molecule, populating an excited
      electronic state of the radical cation. In this state a coherent torsional
      vibration of the bromomethylene groups with a period of 700 fs is started and
      probed by photoinduced fragmentation of the molecular cation. The vibrational
      coherence dephases with the decay of the excited state to the ground state of the
      cation in 1.6 ps. The real-time probing of the excited-state dynamics is made
      possible by exploiting the interaction between the two bromine chromophores and
      its dependence on molecular conformation. This experiment therefore illustrates
      the applicability of the concept of probing ultrafast molecular dynamics using
      the intramolecular interaction between two chromophores.

PMID- 21958193
TI  - Levels of fetuin-A relate to the levels of bone turnover biomarkers in male and
      female patients with type 2 diabetes.
AB  - OBJECTIVE: To evaluate the relationship of plasma fetuin-A levels with markers of
      bone turnover in male and female type 2 diabetic subjects. BACKGROUND: Fetuin-A,
      which is a serum protein produced by the liver and promotes bone mineralization,
      is an independent risk factor for type 2 diabetes, whilst type 2 diabetes is
      associated with an increased incidence of osteoporosis or fractures. It is not
      known how fetuin-A levels relate to parameters of bone metabolism in type 2
      diabetes. DESIGN AND PATIENTS: Eighty patients with type 2 diabetes [40 men and
      40 women matched for age, body mass index (BMI) and time since diagnosis of
      diabetes] were studied. Fetuin-A together with metabolic parameters and levels of
      serum carboxy-terminal telopeptide of type 1 collagen (C-telopeptide),
      osteocalcin, procollagen type 1 amino-terminal propeptide (P1NP), bone alkaline
      phosphatase (ALP) and sex hormones was determined in all participants. RESULTS:
      Fetuin-A levels did not differ significantly between male and female diabetic
      subjects. In a model adjusted for age, BMI, fatty liver index (FLI), time since
      diagnosis of diabetes, HbA(1c) , antidiabetic and lipid-lowering drug therapies,
      smoking, total serum protein, creatinine, gamma glutamyl-transferase, parathyroid
      hormone, C-reactive protein, glomerular filtration rate, and presence of micro-,
      cardio-, and peripheral vascular diabetic complications, fetuin-A showed a
      significant positive association with levels of bone ALP (r = 0.71, P = 0.006) in
      men. In women, fetuin-A was significantly negatively associated with C
      telopeptide (r = -0.60, P = 0.03) levels. CONCLUSIONS: Results suggest an
      independent association of fetuin-A levels with markers of bone turnover in male
      and female patients with type 2 diabetes. More studies are needed to determine
      whether fetuin-A could serve as a new marker for fracture risk or osteoporosis in
      type 2 diabetes and to explore its potential sexually dimorphic effects.

PMID- 21958194
TI  - Constitutive heat shock protein 70 interacts with alpha-enolase and protects
      cardiomyocytes against oxidative stress.
AB  - Constitutive heat shock protein 70 (Hsc70) is a molecular chaperone that has been
      shown to protect cardiomyocytes against oxidative stress. However, the molecular
      mechanism responsible for this protection remains uncertain. To understand the
      mechanism associated with the myocardial protective role of Hsc70, we have
      embarked upon a systematic search for Hsc70-interacting proteins. Using adenosine
      diphosphate (ADP) affinity chromatography and mass spectrometry, we have
      identified alpha-enolase, a rate-limiting enzyme in glycolysis, as a novel Hsc70
      interacting protein in the myocardium of both sham and myocardial ischemia
      reperfused Sprague-Dawley rat hearts. This interaction was confirmed by co
      immunoprecipitation (IP) assays in the myocardial tissues and H9c2 cardiomyocytes
      and protein overlay assay (POA). It was further shown that Hsc70-overexpression
      alleviated the H(2)O(2)-induced decrease of alpha-enolase activity and cell
      damage, and Hsc70 deficiency aggravated the decrease of alpha-enolase activity
      and cell damage in H(2)O(2) treated H9c2 cells. Our research suggests that the
      protective effect of Hsc70 on the cardiomyocytes against oxidative stress is
      partly associated with its interaction with alpha-enolase.

PMID- 21958195
TI  - Acute toxoplasmoses in immunocompetent patients hospitalized in an intensive care
      unit in French Guiana.
AB  - Atypical Toxoplasma gondii strains, unrelated to archetypal clonal lineages (I,
      II, III), have been reported more frequently over the last decade in areas other
      than Europe and North America. A newly described form of toxoplasmosis,
      'Amazonian toxoplasmosis' (AT), has been reported since 2002 in French Guiana. It
      is characterized by severe cases and atypical strains linked to a neotropical
      forest-based cycle. We report on the cases of AT that required intensive care
      management. We performed a prospective observational study on hospitalized adults
      in the Intensive Care Unit (ICU) from 2002 to 2008. Clinical and laboratory data,
      microbiological findings and outcomes were recorded. Data, including the ICU
      simplified acute physiology score and the pneumonia severity index, were
      calculated. Epidemiological risk factors for AT were assessed through
      questionnaires. Eleven non-immunodeficient patients were admitted to the ICU in
      Cayenne for life-threatening pneumonia associated with disseminated
      toxoplasmosis. Mechanical ventilation was necessary in seven patients, four of
      whom required immediate orotracheal intubation. Cardiac and ophthalmological
      abnormalities were found in five and four patients, respectively. One patient
      died from multiple organ failure. The genetic characterization of Toxoplasma DNA
      using six microsatellite markers revealed unique and atypical genotypes in eight
      patients. All patients presented epidemiological risk factors for AT. In French
      Guiana, significant T. gondii-related infectious syndrome associated with the
      lungs, a high level of LDH activity and the reported risk factors for AT was
      strongly suggestive of disseminated toxoplasmosis with a possible trend toward
      life-threatening pneumonia.

PMID- 21958196
TI  - A method for identifying otological drill entanglement with a cotton swab.
AB  - BACKGROUND: The entanglement of the otological drill with cotton swabs is a
      common milling fault in ear surgery. To improve operational safety, this paper
      presents a method for identifying this type of milling fault. METHODS: Force and
      current sensors were installed on a modified otological drill. In accordance with
      the DC motor model and cutting force model, two features of the milling process
      were extracted, namely the characteristic curve and the dynamic relationship
      between the sensor signals. These are complementary features. An adaptive filter
      was designed to fuse them together and output a curve that was sensitive to
      milling faults and was stable during normal milling. Based on the filtering data,
      a rule base is presented for identifying cotton swab entanglement. RESULTS: Five
      surgeons were invited to perform an experiment on calvarian bones. The average
      recognition rate for milling faults was 90%, whereas only 2% of normal millings
      were identified as milling faults. CONCLUSIONS: The presented method could adapt
      to the technique of different surgeons and identify milling faults exactly.

PMID- 21958197
TI  - The revised structure, total synthesis, and absolute configuration of
      streptophenazine A.
AB  - A total synthesis of both diastereomers of the originally proposed structure for
      streptophenazine A (1) has been achieved. However, both synthetic compounds are
      different from the natural product. Re-examination of NMR data reported for
      streptophenazine A and a concise total synthesis of both diastereomers of 17 (17a
      and 17b) led to the structural revision of streptophenazine A to 17b. Asymmetric
      synthesis of (-)-streptophenazine A was also conducted, and its absolute
      configuration was determined to be 1'S,2'R.

PMID- 21958198
TI  - Uptake of di-(2-ethylhexyl) phthalate of vegetables from plastic film
      greenhouses.
AB  - Uptake of di-(2-ethylhexyl) phthalate (DEHP) of nine vegetables including potherb
      mustard, bok choy, celery, spinach, cabbage, leaf of tube, lettuce, garlic, and
      edible amaranth in plastic film greenhouses with different plastic films, film
      thickness, greenhouse age, and greenhouse height was studied. The results showed
      that the higher the DEHP content of film, the thicker the film, the lower the
      height of the greenhouse, and the younger the age of the greenhouse were, the
      higher the DEHP concentration of vegetables was. The results afford significant
      information for production of safe vegetables with low level DEHP contamination.

PMID- 21958200
TI  - Life cycle assessment of potential biojet fuel production in the United States.
AB  - The objective of this paper is to reveal to what degree biobased jet fuels
      (biojet) can reduce greenhouse gas (GHG) emissions from the U.S. aviation sector.
      A model of the supply and demand chain of biojet involving farmers,
      biorefineries, airlines, and policymakers is developed by considering factors
      that drive the decisions of actors (i.e., decision-makers and stakeholders) in
      the life cycle stages. Two kinds of feedstock are considered: oil-producing
      feedstock (i.e., camelina and algae) and lignocellulosic biomass (i.e., corn
      stover, switchgrass, and short rotation woody crops). By factoring in
      farmer/feedstock producer and biorefinery profitability requirements and risk
      attitudes, land  availability and suitability, as well as a time delay and
      technological learning factor, a more realistic estimate of the level of biojet
      supply and emissions reduction can be developed under different oil price
      assumptions. Factors that drive biojet GHG emissions and unit production costs
      from each feedstock are identified and quantified. Overall, this study finds that
      at likely adoption rates biojet alone would not be sufficient to achieve the
      aviation emissions reduction target. In 2050, under high oil price scenario
      assumption, GHG emissions can be reduced to a level ranging from 55 to 92%, with
      a median value of 74%, compared to the 2005 baseline level.

PMID- 21958199
TI  - Self-rated health does not predict 10-year weight change among middle-aged adults
      in a longitudinal population study.
AB  - BACKGROUND: There is a worldwide obesity epidemic, but lack of a simple method,
      applicable for research or clinical use, to identify individuals at high risk of
      weight gain. Therefore, the relationship of self-rated health and 10-year percent
      weight change was evaluated to determine if self-rated health would predict
      weight change. METHODS: From 1990 to 2008, adults aged 30, 40, 50 and 60 years
      were invited to health surveys that included self-rated health and measured
      weight and height. ANOVA was used to evaluate the relationship of 10-year percent
      weight change and self-rated health. RESULTS: The study population consisted of
      29,207 participants (46.5% men). There was no relationship between baseline self
      rated health and 10-year percent weight change for middle-aged men or women.
      CONCLUSIONS: Self-rated health is not able to predict weight change over a 10
      year period in this age group.

PMID- 21958201
TI  - Fast folding of RNA pseudoknots initiated by laser temperature-jump.
AB  - RNA pseudoknots are examples of minimal structural motifs in RNA with tertiary
      interactions that stabilize the structures of many ribozymes. They also play an
      essential role in a variety of biological functions that are modulated by their
      structure, stability, and dynamics. Therefore, understanding the global
      principles that determine the thermodynamics and folding pathways of RNA
      pseudoknots is an important problem in biology, both for elucidating the folding
      mechanisms of larger ribozymes as well as addressing issues of possible kinetic
      control of the biological functions of pseudoknots. We report on the
      folding/unfolding kinetics of a hairpin-type pseudoknot obtained with microsecond
      time-resolution in response to a laser temperature-jump perturbation. The
      kinetics are monitored using UV absorbance as well as fluorescence of
      extrinsically attached labels as spectroscopic probes of the transiently
      populated RNA conformations. We measure folding times of 1-6 ms at 37  degrees C,
      which are at least 100-fold faster than previous observations of very slow
      folding pseudoknots that were trapped in misfolded conformations. The measured
      relaxation times are remarkably similar to predictions of a computational study
      by Thirumalai and co-workers (Cho, S. S.; Pincus, D.L.; Thirumalai, D. Proc.
      Natl. Acad. Sci. U. S. A. 2009, 106, 17349-17354). Thus, these studies provide
      the first observation of a fast-folding pseudoknot and present a benchmark
      against which computational models can be refined.

PMID- 21958202
TI  - Enantioselective synthesis of 4-substituted 4,5-dihydro-1H-[1,5]benzodiazepin
      2(3H)-ones by the Lewis base-catalyzed hydrosilylation.
AB  - Enantioselective synthesis of 4-substituted 4,5-dihydro-1H-[1,5]benzodiazepin
      2(3H)-ones has been accomplished through chiral Lewis base-catalyzed
      hydrosilylation. The corresponding products were obtained in excellent yields (up
      to 99%) and enantioselectivities (up to 98%). The absolute configuration of
      product 3n has been determined as S by X-ray crystallographic analysis.

PMID- 21958203
TI  - A proposed adaptation of the European Foundation for Quality Management
      Excellence Model to physical activity programmes for the elderly - development of
      a quality self-assessment tool using a modified Delphi process.
AB  - BACKGROUND: There has been a growing concern in designing physical activity (PA)
      programmes for elderly people, since evidence suggests that such health promotion
      interventions may reduce the deleterious effects of the ageing process. Complete
      programme evaluations are a necessary prerequisite to continuous quality
      improvements. Being able to refine, adapt and create tools that are suited to the
      realities and contexts of PA programmes for the elderly in order to support its
      continuous improvement is, therefore, crucial. Thus, the aim of this study was to
      develop a self-assessment tool for PA programmes for the elderly. METHODS: A 3
      round Delphi process was conducted via the Internet with 43 national experts in
      PA for the elderly, management and delivery of PA programmes for the elderly,
      sports management, quality management and gerontology, asking experts to identify
      the propositions that they considered relevant for inclusion in the self
      assessment tool. Experts reviewed a list of proposed statements, based on the
      criteria and sub-criteria from the European Foundation for Quality Management
      Excellence Model (EFQM) and PA guidelines for older adults and rated each
      proposition from 1 to 8 (disagree to agree) and modified and/or added
      propositions. Propositions receiving either bottom or top scores of greater than
      70% were considered to have achieved consensus to drop or retain, respectively.
      RESULTS: In round 1, of the 196 originally-proposed statements (best practice
      principles), the experts modified 41, added 1 and achieved consensus on 93. In
      round 2, a total of 104 propositions were presented, of which experts modified 39
      and achieved consensus on 53. In the last round, of 51 proposed statements, the
      experts achieved consensus on 19. After 3 rounds of rating, experts had not
      achieved consensus on 32 propositions. The resulting tool consisted of 165
      statements that assess nine management areas involved in the development of PA
      programmes for the elderly. CONCLUSION: Based on experts' opinions, a self
      assessment tool was found in order to access quality of PA programmes for the
      elderly. Information obtained with evaluations would be useful to organizations
      seeking to improve their services, customer satisfaction and, consequently,
      adherence to PA programmes, targeting the ageing population.

PMID- 21958204
TI  - Enterovirus 68 infection in children with asthma attacks: virus-induced asthma in
      Japanese children.

PMID- 21958205
TI  - Analysis of a polydisperse polyrotaxane based on poly(ethylene oxide) and alpha
      cyclodextrins using nanoelectrospray and LTQ-Orbitrap.
AB  - Polyrotaxanes (PR) are among the most studied interlocked molecules in the field
      of supramolecular chemistry. Cyclodextrin based polyrotaxanes (CD based PRs) are
      well-known to be difficult to analyze by mass spectrometry (MS). Nanoelectrospray
      (nanoESI) employed during mass spectrometry (MS) and tandem mass spectrometry
      (MS/MS) experiments turns out to be particularly useful to analyze these
      noncovalent assemblies. While ESI/nanoESI based spectra usually contain
      multicharged species which greatly complicate the interpretation, particularly
      for such complex mixtures analysis, the hyphenation with a high resolution
      analyzer such as Orbitrap could overcome this limitation. This Article reports
      efforts to achieve a detailed structural deciphering by nanoESI-MS and nanoESI
      MS/MS of CD based PRs constituted of alphaCDs, unmodified or surrounded by 1 or 2
      sulfation(s), which were threaded along polydisperse poly(ethylene oxide)
      alpha,omega-dipyrenyl chains. The described method is more sensitive and less
      sample consuming than a typical NMR experiment and in good agreement with size
      exclusion chromatography (SEC) results. Moreover, as compared to MALDI-TOF MS
      analysis, all populations were presumably elucidated without discrimination
      effect. Therefore, this MS development allowed us to estimate the PR sample
      content with 16 to 35 ethylene oxide units, 1 to 5 alphaCDs threaded, and 0 to 10
      sulfo groups grafted on the overall CDs. Finally, the method afforded the
      possibility to unambiguously attribute supramolecular architectures from
      2276.0278 to 7767.8342 g.mol(-1) corresponding to poly[2]- to poly[6]rotaxanes.

PMID- 21958206
TI  - Letter string processing and visual short-term memory.
AB  - The present study investigated whether expertise with letter string processing
      influences visual short-term memory capacity. Specifically, we examined whether
      performance in a change-detection task would vary as a function of stimulus type
      (letters vs. symbols) and type of display (horizontal, vertical, and circular).
      Participants were asked to detect a one-character change in a briefly presented
      character array following a delay of 900 ms. Concurrent articulation was used to
      limit effects of rehearsal. Type of display significantly affected performance
      with letters, but not with symbols, with a selective increase in change-detection
      accuracy for horizontally presented letter arrays compared with vertical and
      circular arrays. These findings confirm the standard limits of storage in visual
      short-term memory, but critically reveal a selective advantage for letter arrays
      over symbol arrays when presented horizontally. Such an advantage is probably due
      to the utilization of a specialized encoding mechanism built up over years of
      reading experience.

PMID- 21958207
TI  - Syngeneic hematopoietic stem cell transplantation enhances the antitumor immunity
      of intratumoral type I interferon gene transfer for sarcoma.
AB  - Sarcoma at advanced stages remains a clinically challenging disease. Interferons
      (IFNs) can target cancer cells by multiple antitumor activities, including the
      induction of cancer cell death and enhancement of immune response. However, the
      development of an effective cancer immunotherapy is often difficult, because
      cancer generates an immunotolerant microenvironment against the host immune
      system. An autologous hematopoietic stem cell transplantation (HSCT) is expected
      to reconstitute a fresh immune system, and expand tumor-specific T cells through
      the process of homeostatic proliferation. Here we examined whether a combination
      of autologous HSCT and IFNs could induce an effective tumor-specific immune
      response against sarcoma. First, we found that a type I IFN gene transfer
      significantly suppressed the cell growth of various sarcoma cell lines, and that
      IFN-beta gene transfer was more effective in inducing cell death than was IFN
      alpha in sarcoma cells. Then, to examine the antitumor effect in vivo, human
      sarcoma cells were inoculated in immune-deficient mice, and a lipofection of an
      IFN-beta-expressing plasmid was found to suppress the growth of subcutaneous
      tumors significantly. Finally, the IFN gene transfer was combined with syngeneic
      HSCT in murine osteosarcoma models. Intratumoral IFN-beta gene transfer markedly
      suppressed the growth of vector-injected tumors and inhibited formation of
      spontaneous lung and liver metastases in syngeneic HSCT mice, and an infiltration
      of many immune cells was recognized in metastatic tumors of the treated mice. The
      treated mice showed no significant adverse events. A combination of intratumoral
      IFN gene transfer with autologous HSCT could be a promising therapeutic strategy
      for patients with sarcoma.

PMID- 21958209
TI  - Detection, advice, and referral to services (DARTS) procedures among clients with
      public defenders.
AB  - Although screening and brief intervention techniques have been found to be
      efficacious in a variety of medical settings, their use in the criminal justice
      system has been limited. We present data from Chief Public Defenders (PDs) in 24
      Pennsylvania counties who were surveyed about their approach to substance-using
      clients and their attitudes toward treatment and talking to clients about
      substance use. A random subsample (n = 8) participated in an additional
      semistructured interview. Results provide preliminary support for the use of
      Detection, Advice, and Referral to Services (DARTS) procedures by PDs and
      identify potential barriers to its implementation.

PMID- 21958208
TI  - Experimental annotation of the human pathogen Histoplasma capsulatum transcribed
      regions using high-resolution tiling arrays.
AB  - BACKGROUND: The fungal pathogen Histoplasma capsulatum is thought to be the most
      common cause of fungal respiratory infections in immunocompetent humans, yet
      little is known about its biology. Here we provide the first genome-wide studies
      to experimentally validate its genome annotation. A functional interrogation of
      the Histoplasma genome provides critical support for continued investigation into
      the biology and pathogenesis of H. capsulatum and related fungi. RESULTS: We
      employed a three-pronged approach to provide a functional annotation for the H.
      capsulatum G217B strain. First, we probed high-density tiling arrays with labeled
      cDNAs from cells grown under diverse conditions. These data defined 6,172
      transcriptionally active regions (TARs), providing validation of 6,008 gene
      predictions. Interestingly, 22% of these predictions showed evidence of anti
      sense transcription. Additionally, we detected transcription of 264 novel genes
      not present in the original gene predictions. To further enrich our analysis, we
      incorporated expression data from whole-genome oligonucleotide microarrays. These
      expression data included profiling under growth conditions that were not
      represented in the tiling experiment, and validated an additional 2,249 gene
      predictions. Finally, we compared the G217B gene predictions to other available
      fungal genomes, and observed that an additional 254 gene predictions had an
      ortholog in a different fungal species, suggesting that they represent genuine
      coding sequences. CONCLUSIONS: These analyses yielded a high confidence set of
      validated gene predictions for H. capsulatum. The transcript sets resulting from
      this study are a valuable resource for further experimental characterization of
      this ubiquitous fungal pathogen. The data is available for interactive
      exploration at http://histo.ucsf.edu.

PMID- 21958210
TI  - Role of functional polymorphism of matrix metalloproteinase-2 (-1306 C/T and -168
      G/T) and MMP-9 (-1562 C/T) promoter in oral submucous fibrosis and head and neck
      squamous cell carcinoma in an Indian population.
AB  - The aim of this study was to explore the association of MMP-2 (-1306 C/T and -168
      G/T) and MMP-9 (-1562 C/T) promoter polymorphisms in oral submucous fibrosis
      (OSMF) and head and neck squamous cell carcinoma (HNSCC) cases. These SNP were
      genotyped by PCR-RFLP. Total of 1260 individuals were recruited, of which 412
      OSMF, 422 HNSCC and 426 were controls. In HNSCC, MMP-2 (-1306 C/T) and MMP-9 (
      1562C/T) polymorphism, T allele showed strong association (p < 0.00 and p < 0.01)
      as compared to healthy control respectively, but not in case of OSMF and showed
      significant association with increasing progression of clinico-pathological
      grading. We concluded that SNPs in the MMP-2 and -9 promoter region may be
      associated with susceptibility to HNSCC not in OSMF.

PMID- 21958211
TI  - Effect of pollen from Typha angustata on hydrogen peroxide induced toxicity in
      osteoblastic MC3T3-E1 cells.
AB  - BACKGROUND: Typha angustata is a traditional Chinese medicine, commonly used for
      a variety of clinical disorders, including atherosclerosis and wound healing. In
      the present study, the protective effects of T. angustata pollen extract (TE) on
      the response of osteoblast to oxidative stress were evaluated. MATERIALS AND
      METHODS: Osteoblastic MC3T3-E1 cells were incubated with H(2)O(2) and/or TE, and
      markers of osteoblast function and oxidative damage were examined. RESULTS: TE
      treatment significantly (P < 0.05) reversed the cytotoxic effect of H(2)O(2) and
      this effect was blocked by ICI182780, suggesting that TE's effect might be partly
      involved in estrogen action. TE significantly (P < 0.05) increased collagen
      content, alkaline phosphatase activity, calcium deposition of osteoblasts in the
      presence of H(2)O(2) and these effects were blocked by rottlerin and PD98059,
      suggesting that the induction of differentiation by TE is associated with
      increased activation of protein kinase C and ERK. Moreover, H(2)O(2)-induced
      reduction of osteocalcin was significantly recovered in the presence of TE.
      Pretreatment with TE also decreased the increase in receptor activator of nuclear
      factor-kB ligand, malondialdehyde, and protein carbonyl induced by H(2)O(2).
      CONCLUSION: These results suggest that the pollen of T. angustata may be useful
      for the protection of H(2)O(2)-induced oxidative damage and dysfunction in
      osteoblasts.

PMID- 21958212
TI  - Antioxidative activity of propolis extract in yeast cells.
AB  - The antioxidative activities of propolis and its main phenolic compounds, caffeic
      acid, p-coumaric acid, ferulic acid, and caffeic acid phenethyl ester, were
      investigated in the yeast Saccharomyces cerevisiae. After 1 h of exposure of the
      yeast cells, their intracellular oxidation was measured using 2',7'
      dichlorofluorescein. Yeast cells exposed to 96% ethanolic extracts of propolis in
      DMSO (EEP) showed decreased intracellular oxidation, with no significant
      differences seen for the individual phenolic compounds. However, cellular uptake
      was seen only for a moderately polar fraction of EEP (E2) and caffeic acid
      phenethyl ester. The EEP antioxidative activity thus resulted from this E2
      fraction of EEP. The influence of EEP was also investigated at the mitochondrial
      proteome level, by analyzing its profile after 1 h of exposure of the yeast cells
      to EEP and E2. Changes in the levels of antioxidative proteins and proteins
      involved in ATP synthesis were seen.

PMID- 21958213
TI  - Mycobacterium tuberculosis Sonicate-Induced IFNgamma, CXCL10 and IL10 can
      Differentiate Severity in Tuberculosis.
AB  - Improved tools are required to study immunopathogenesis of tuberculosis (TB).
      Mycobacterium tuberculosis antigen-stimulated T cell-based assays can detect TB
      but are less effective when responses are compromised such as in severe disease.
      We investigated immune responses to M. tuberculosis whole sonicate (MTBs),
      recombinant antigens ESAT6 and CFP10 in whole blood cells of healthy endemic
      controls (EC, n = 42) and patients with pulmonary (PTB, n = 36) or extrapulmonary
      (ETB, n = 41) disease. Biomarkers of T cell activation (IFNgamma) or modulation
      (IL10) and chemokines, CXCL9, CXCL10 and CCL2, secretion were measured. MTBs,
      ESAT6 and CFP10 all induced IFNgamma responses in TB. ESAT6-induced IFNgamma was
      elevated in TB as compared with EC. MTBs stimulated the highest IFNgamma levels
      but did not differentiate between TB and EC. However, MTBs-induced CXCL10 (P =
      0.004) was reduced, while IL10 (P < 0.001) was raised in TB as compared with EC.
      Between sites, MTBs-induced CCL2 (P = 0.001) and IL10 secretion was higher in PTB
      than ETB (P < 0.001). In comparison of disease severity, MTBs-induced IFNgamma (P
      = 0.014) and CXCL10 (P = 0.022) levels were raised in moderate as compared with
      far advanced PTB. In ETB, MTBs-induced IL10 levels were greater in less-severe (L
      ETB) than in severe disseminated (D-ETB) cases, P = 0.035. Within the L-ETB
      group, MTBs-induced IFNgamma was greater in patients with tuberculous
      lymphadenitis than those with pleural TB (P = 0.002). As immune responses to MTBs
      were differentially activated in TB of different sites and severity, we propose
      the utility of MTBs-induced IFNgamma, CXCL10 and IL10 as biomarkers in TB.

PMID- 21958214
TI  - A small molecule mimicking a phosphatidylinositol (4,5)-bisphosphate binding
      pleckstrin homology domain.
AB  - Inositol phospholipids have emerged as important key players in a wide variety of
      cellular functions. Among the seven existing inositol phospholipids,
      phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P(2)) has attracted much
      attention in recent years due to its important role in numerous cellular
      signaling events and regulations, which in turn impact several human diseases.
      This particular lipid is recognized in the cell by specific lipid binding
      domains, such as the Pleckstrin-homology (PH) domain, which is also employed as a
      tool to monitor this important lipid. Here, we describe the synthesis and
      biological characterization of a small molecule that mimics the PH domain as
      judged by its ability to bind specifically to only PI(4,5)P(2) and effectively
      compete with the PH domain in vitro and in a cellular environment. The binding
      constant of this small molecule PH domain mimetic (PHDM) was determined to be
      17.6 +/- 10.1 MUM, similar in potency to the PH domain. Using NIH 3T3 mouse
      fibroblast cells we demonstrated that this compound is cell-permeable and able to
      modulate PI(4,5)P(2)-dependent effects in a cellular environment such as the
      endocytosis of the transferrin receptor, loss of mitochondria, as well as stress
      fiber formation. This highly PI(4,5)P(2)-specific chemical mimetic of a PH domain
      not only is a powerful research tool but might also be a lead compound in future
      drug developments targeting PI(4,5)P(2)-dependent diseases such as Lowe syndrome.

PMID- 21958215
TI  - Adaptation to survival in germinal center is the initial step in onset of
      indolent stage of multiple myeloma.
AB  - Aberrant mutations of centrocytes in germinal centers (GC) can generate two
      completely different diseases: B-cell lymphomas and monoclonal gammopathy of
      undetermined significance (MGUS). In this article we use computational models to
      examine the evolutionary dynamics by which initial adaptation to survival in the
      GC allows naive MGUS cells to proliferate in the bone marrow and initiate the
      evolutionary process that will lead to aggressive multiple myeloma (MM). Our
      simulations show that MGUS cells may generate bone marrow tumors ranging from
      indolent to aggressive, depending on the original adaptation in the GC. All these
      tumors, however, are limited to approximately 15% of the marrow cellularity due
      to hypoxia-induced quiescence (this correlates with the cellularity that
      separates MGUS and MM, ~10%). Resistance to hypoxia-induced quiescence and cell
      death was one of the two major bone marrow adaptations that allowed continued
      tumor growth and establishment of paracrine cytokine loops, known to increase MM
      cell replication and de novo multidrug resistance. The second major adaptation
      was an increase in IL-6-independent growth rate, which correlates with the
      mutations observed in advanced stage patients. Even though there was an increase
      in the microvessel density in all simulations, the "angiogenic switch" was not
      due to a MM angiogenic phenotype, but rather the response of MM cells to the
      regional hypoxia caused by the increased tumor burden. These results indicate
      that treatments targeting the adaptation to survival and proliferation in
      hypoxia, in conjunction with currently available therapies, may have synergistic
      effects, by delaying tumor growth and reducing cytokine paracrine loops mediated
      by angiogenic factors.

PMID- 21958216
TI  - Identification of pyrido[1,2-alpha]pyrimidine-4-ones as new molecules improving
      the transcriptional functions of estrogen-related receptor alpha.
AB  - The nuclear estrogen-related receptor alpha (ERRalpha) plays a central role in
      the regulation of expression of the genes involved in mitochondrial biogenesis
      and oxidative metabolism. We have successfully identified a series of pyrido[1,2
      a]pyrimidin-4-ones as new agonists enhancing the transcriptional functions of
      ERRalpha. The compounds potently elevated the mRNA levels and the protein levels
      of ERRalpha downstream targets. Consequently, the compounds improved the glucose
      and fatty acid uptake in C2C12 muscle cells.

PMID- 21958217
TI  - Estimation of disease incidence in claims data dependent on the length of follow
      up: a methodological approach.
AB  - OBJECTIVE: To analyze the impact of the length of disease-free intervals on
      incidence estimation. DATA SOURCE: Statutory health insurance sample in Germany.
      STUDY DESIGN: Overestimation of the incidence in the first quarter of 2008 for
      three selected diseases, diabetes mellitus, colorectal cancer, and heart failure,
      depending on different lengths of preceding disease-free intervals. DATA
      COLLECTION/EXTRACTION METHODS: Continuously insured from 2000 until 2008 >= 18
      years (N = 144,907). PRINCIPAL FINDINGS: Compared with an 8-year disease-free
      period, incidence overestimations for diabetes, colorectal cancer, and heart
      failure were 40, 23, and 43 percent defining a 1-year, and 5, 9, and 5 percent
      defining a 5-year disease-free period, respectively. CONCLUSIONS: Depending on
      the specific disease, caution has to be taken while using short disease-free
      periods because incidence estimates may be extremely overestimated.

PMID- 21958218
TI  - Factors contributing to the glass-forming ability of a simulated molecular
      liquid.
AB  - The time scales of crystallization of two model liquids, an atomic liquid and a
      molecular liquid of bent trimers originally introduced as a model of the glass
      the former o-terphenyl, are determined using molecular dynamics simulations. The
      molecular liquid is found to have a minimum crystallization time, on
      supercooling, that is 10(4) times larger than that of the atomic liquid. We
      present evidence that this enhanced glass-forming ability is due, in equal parts,
      to the slower dynamics and the larger crystal-liquid interfacial free energy in
      the molecular liquid.

PMID- 21958219
TI  - High genetic diversity including potential new subtypes of hepatitis C virus
      genotype 6 in Lao People's Democratic Republic.
AB  - Sera from 105 anti-HCV-positive first-time blood donors collected in 2004, 2005
      and 2008 in different provinces in Laos were investigated by PCR. Forty-five
      samples were positive for HCV (42.86%); two belonged to subtype 1b (2/45, 4.4%)
      and all others to genotype 6 (43/45, 95.6%), including subtypes 6b, 6h, 6k, 6l,
      6n and 6q. Three groups of sequences were not clearly attributable to any
      genotype 6 subtype, two of which may be regarded as candidates for new subtypes
      of genotype 6. Two samples were mixed infected with different subtypes or
      clusters of genotype 6 viruses.

PMID- 21958220
TI  - NOX2 activated by alpha1-adrenoceptors modulates hepatic metabolic routes
      stimulated by beta-adrenoceptors.
AB  - The NADPH oxidase (NOX) family of enzymes oxidase catalyzes the transport of
      electrons from NADPH to molecular oxygen and generates O(2)(*-), which is rapidly
      converted into H(2)O(2). We aimed to identify in hepatocytes the protein NOX
      complex responsible for H(2)O(2) synthesis after alpha(1)-adrenoceptor (alpha(1)
      AR) stimulation, its activation mechanism, and to explore H(2)O(2) as a potential
      modulator of hepatic metabolic routes, gluconeogenesis, and ureagenesis,
      stimulated by the ARs. The dormant NOX2 complex present in hepatocyte plasma
      membrane (HPM) contains gp91(phox), p22(phox), p40(phox), p47(phox), p67(phox)
      and Rac 1 proteins. In HPM incubated with NADPH and guanosine triphosphate (GTP),
      alpha(1)-AR-mediated H(2)O(2) synthesis required all of these proteins except for
      p40(phox). A functional link between alpha(1)-AR and NOX was identified as the
      Galpha(13) protein. Alpha(1)-AR stimulation in hepatocytes promotes Rac1-GTP
      generation, a necessary step for H(2)O(2) synthesis. Negative cross talk between
      alpha(1)-/beta-ARs for H(2)O(2) synthesis was observed in HPM. In addition,
      negative cross talk of alpha(1)-AR via H(2)O(2) to beta-AR-mediated stimulation
      was recorded in hepatocyte gluconeogenesis and ureagenesis, probably involving
      aquaporine activity. Based on previous work we suggest that H(2)O(2), generated
      after NOX2 activation by alpha(1)-AR lightening in hepatocytes, reacts with cAMP
      dependent protein kinase A (PKA) subunits to form an oxidized PKA, insensitive to
      cAMP activation that prevented any rise in the rate of gluconeogenesis and
      ureagenesis.

PMID- 21958221
TI  - Double-plating of ovine critical sized defects of the tibia: a low morbidity
      model enabling continuous in vivo monitoring of bone healing.
AB  - BACKGROUND: Recent studies using sheep critical sized defect models to test
      tissue engineered products report high morbidity and complications rates. This
      study evaluates a large bone defect model in the sheep tibia, stabilized with
      two, a novel Carbon fibre Poly-ether-ether-ketone (CF-PEEK) and a locking
      compression plate (LCP) which could sustain duration for up to 6 month with an
      acceptable low complication rate. METHODS: A large bone defect of 3 cm was
      performed in the mid diaphysis of the right tibia in 33 sheep. The defect was
      stabilised with the CF - PEEK plate and an LCP. All sheep were supported with
      slings for 8 weeks after surgery. The study was carried out for 3 months in 6 and
      for 6 months in 27 animals. RESULTS: The surgical procedure could easily be
      performed in all sheep and continuous in vivo radiographic evaluation of the
      defect was possible. This long bone critical sized defect model shows with 6.1% a
      low rate of complications compared with numbers mentioned in the literature.
      CONCLUSIONS: This experimental animal model could serve as a standard model in
      comparative research. A well defined standard model would reduce the number of
      experimental animals needed in future studies and would therefore add to ethical
      considerations.

PMID- 21958223
TI  - Recognizing and managing the complications of prostate biopsy.

PMID- 21958222
TI  - Mesenchymal stromal cell-conditioned medium prevents radiation-induced small
      intestine injury in mice.
AB  - BACKGROUND AIMS: Effective therapy for radiation-induced intestinal injury is
      currently unavailable. Mesenchymal stromal cells (MSC) are expected to be useful
      in repairing intestinal damage caused by irradiation. We determined whether the
      MSC-derived bioactive components could protect radiation-induced small intestine
      injury in mice. METHODS: Human umbilical cord (UC)-derived MSC were isolated,
      expanded and exposed to hypoxic conditions in vitro. The hypoxia-conditioned
      medium was ultrafiltrated with a 3-kDa molecular weight cut-off to prepare the
      high molecular weight fraction (HMWF). The effect of HMWF on the viability of
      irradiated rat intestinal epithelial cells (IEC-6) was examined by MTT(methyl
      thiazolyl tetrazolium) assay. HMWF was also delivered to BALB/C male mice by tail
      intravenous injection immediately after receiving local abdominal irradiation at
      a selected dose of 10 Gy. Animal body weight, survival and diarrhea were
      monitored for 30 days. The improvement of mice intestine structure, including
      epithelium thickness and villus height, was examined by histology. RESULTS: HMWF
      enhanced the viability of irradiated IEC-6 cells in vitro. Repeated infusion of
      HMWF for 7 days immediately after abdominal irradiation of 10 Gy ((60)Cogamma
      ray) increased the survival rate, decreased diarrhea occurrence and improved the
      small intestinal structural integrity of irradiated mice. CONCLUSIONS: MSC
      derived bioactive components could be a novel therapeutic approach for the
      treatment of radiation-induced injury.

PMID- 21958224
TI  - How Chester Alan Arthur 'brightened' from a political spoilsman to a civil
      service reformer.

PMID- 21958225
TI  - Laparoscopic transposition of lower pole crossing vessels ('vascular hitch') in
      pure extrinsic pelvi-ureteric junction (PUJ) obstruction in children.

PMID- 21958228
TI  - Synthesis of alpha,alpha-disubstituted aryl amines by rhodium-catalyzed amination
      of tertiary allylic trichloroacetimidates.
AB  - The rhodium-catalyzed regioselective amination of tertiary allylic
      trichloroacetimidates with unactivated aromatic amines is a direct and efficient
      approach to the preparation of alpha,alpha-disubstituted allylic aryl amines in
      good yield and with excellent regioselectivity. This method is applicable to a
      variety of unactivated primary and secondary amines and allows for the
      preparation of reverse prenylated indoles in two steps.

PMID- 21958229
TI  - Combined serum proteomic and metabonomic profiling after laparoscopic sleeve
      gastrectomy in children and adolescents.
AB  - AIM: The consequences of bariatric surgery on important metabolic and signaling
      pathways are still poorly understood. The aim of our study was to unravel the
      network of metabolic changes and obesity-related protein biomarkers in morbidly
      obese children and adolescents undergoing laparoscopic sleeve gastrectomy (LSG).
      METHODS: In a prospective study, 6 children with morbid obesity who had failed a
      well-established conservative weight loss therapy underwent LSG. Pre- and 6
      months postoperatively, a metabonomic profiling of 163 metabolites by mass
      spectrometry and protein profiling by ELISA (clusterin [CLU], pigment epithelium
      derived factor [PEDF], retinol binding protein 4 [RBP4], paraoxonase 1 [PON1])
      was performed to identify biomarkers of important pathways. RESULTS: At referral
      for surgery, the mean age was 14.5 years (range 8-17), mean body mass index (BMI
      in kg/m(2)) was 48.13 (range 41.1-56.3). All patients showed various metabolic
      comorbidities. LSG was uneventful in all of them. At 6 months postsurgery, the
      mean BMI has dropped to 37.1 (range 28.4-40.6). Targeted serum metabonomics
      resulted in 7 metabolites, which were significantly affected by LSG. Among those,
      the amino acid phenylalanine was increased, and methionine decreased. The glycero
      phospatidylcholine PCaaC38:5 were upregulated, and PCaaC40:2 and PCaaC42:1 were
      down regulated after 6 months compared with baseline. Further, sphingomyoline
      (SM) C26:0 and SM C26:1 were decreased after 6 months. The obesity-related
      biomarkers CLU, PEDF, and RBP4 were decreased, whereas PON1 levels were
      increased. CONCLUSION: LSG leads to changes in amino acids and in lipid
      metabolism indicated by glycerol-phosphatidylcholines and SM. The pattern of
      protein biomarkers and metabolites might provide measures for the induced
      physiological changes and for therapy monitoring.

PMID- 21958230
TI  - Numerical solution of the Polanyi-DR isotherm in linear driving force models.
AB  - The Polanyi-Dubinin-Radushkevich isotherm has proven useful for modeling the
      adsorption of volatile organic compounds on microporous materials such as
      activated carbon. When embedded in a larger dynamic simulation--e.g., of whole
      building pollutant transport--it is important to solve the sorption relations as
      quickly as possible. This work compares numerical methods for solving the Polanyi
      DR model, in cases where transport to the surface is assumed linear in the bulk
      to-surface concentration differences. We focus on developing numerically stable
      algorithms that converge across a wide range of inputs, including zero
      concentrations, where the isotherm is undefined. We identify several methods,
      including a modified Newton-Raphson search, that solve the system 3-4 times
      faster than simple bisection. Finally, we present a rule of thumb for identifying
      when boundary-layer diffusion limits the transport rate enough to justify
      reducing the model complexity.

PMID- 21958231
TI  - Design and validation of a high-throughput matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry method for quantification of hepcidin
      in human plasma.
AB  - Disorders of iron metabolism affect over a billion people worldwide. The
      circulating peptide hormone hepcidin, the central regulator of iron distribution
      in mammals, holds great diagnostic potential for an array of iron-associated
      disorders, including iron loading (beta-thalassemia), iron overload (hereditary
      hemochromatosis), and iron deficiency diseases. We describe a novel high
      throughput matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF)
      mass spectrometry assay for quantification of hepcidin in human plasma. This
      assay involves enrichment using a functionalized MALDI chip, a novel solvent
      detergent precipitation buffer, and quantification using a stable isotope labeled
      internal standard. The linear range of hepcidin in plasma was 1-120 nM, with a
      low limit of quantification (LOQ) (1 nM), high accuracy (<15% relative error
      (RE)), and high precision (intraday average 5.52-18.48% coefficient of variation
      (CV) and interday 9.32-14.83% CV). The assay showed strong correlation with an
      established hepcidin immunoassay (Spearman; R(2) = 0.839 n = 93
      ethylenediaminetetraacetic acid (EDTA) plasma). A collection of normal healthy
      pediatric samples (range 3.8-32.5 ng/mL; mean 12.9 ng/mL; n = 119) showed
      significant differences from an adult collection (range 1.8-48.7 ng/mL; mean 16.1
      ng/mL; n = 95; P = 0.0096). We discuss these preliminary reference ranges and
      correlations with additional parameters in light of the utility and limitations
      of hepcidin measurements as a stand-alone diagnostic and as a tool for
      therapeutic intervention.

PMID- 21958232
TI  - Total synthesis of alpha-1C-galactosylceramide, an immunostimulatory C
      glycosphingolipid, and confirmation of the stereochemistry in the first
      generation synthesis.
AB  - A nonisosteric alpha-C-glycoside analogue of KRN7000 (alpha-1C-GalCer, 1) was
      reported to induce a selective type of cytokine release in human invariant
      natural killer cells in vitro. We report here a very concise synthetic route to 1
      and its analogue 1'. The key steps include olefin cross-metathesis, Sharpless
      asymmetric epoxidation, and epoxide opening by NaN(3)/NH(4)Cl. Inversion of
      configuration at the amide-bearing carbon in the phytosphingosine backbone
      constructed by epoxide opening in our previous synthesis of 1 was verified,
      indicating that remote group participation is not involved during the epoxide
      opening reaction.

PMID- 21958233
TI  - Mediators of physical activity change in a behavioral modification program for
      type 2 diabetes patients.
AB  - BACKGROUND: Many studies have reported significant behavioral impact of physical
      activity interventions. However, few have examined changes in potential mediators
      of change preceding behavioral changes, resulting in a lack of information
      concerning how the intervention worked. Our purpose was to examine mediation
      effects of changes in psychosocial variables on changes in physical activity in
      type 2 diabetes patients. METHODS: Ninety-two patients (62 +/- 9 years, 30, 0 +/-
      2.5 kg/m(2), 69% males) participated in a randomized controlled trial. The 24
      week intervention was based on social-cognitive constructs and consisted of a
      face-to-face session, telephone follow-ups, and the use of a pedometer. Social
      cognitive variables and physical activity (device-based and self-reported) were
      collected at baseline, after the 24-week intervention and at one year post
      baseline. PA was measured by pedometer, accelerometer and questionnaire. RESULTS:
      Post-intervention physical activity changes were mediated by coping with relapse,
      changes in social norm, and social modeling from family members (p <= 0.05). One
      year physical activity changes were mediated by coping with relapse, changes in
      social support from family and self-efficacy towards physical activity barriers
      (p <= 0.05) CONCLUSIONS: For patients with type 2 diabetes, initiatives to
      increase their physical activity could usefully focus on strategies for resuming
      regular patterns of activity, on engaging family social support and on building
      confidence about dealing with actual and perceived barriers to activity. TRIAL
      REGISTRATION: NCT00903500, ClinicalTrials.gov.

PMID- 21958234
TI  - Adolescent-parent disagreement on health-related quality of life of food-allergic
      adolescents: who makes the difference?
AB  - BACKGROUND: Food-allergic adolescents are at highest risk for food allergy
      fatalities, which may be partly due to compromised self-management behavior. Such
      behavior may be negatively influenced by conflictual situations caused by
      adolescent-parent disagreement on the adolescent's health-related quality of life
      (HRQL). Comparisons of adolescent-self-reported and parent-proxy-reported HRQL of
      food-allergic adolescents have never extensively been studied. The aims of this
      study were to investigate disagreement in adolescent-self-reports and parent
      proxy-reports on the HRQL of food-allergic adolescents and to investigate the
      factors influencing adolescent-parent disagreement. METHODS: Teenager Form (TF)
      and Parent Form (PFA) of the Food Allergy Quality of Life Questionnaire (FAQLQ),
      Food Allergy Independent Measure (FAIM), and Brief-Illness Perception
      Questionnaire (Brief-IPQ) were sent to food-allergic Dutch adolescents (13-17
      years) and their parents. ICCs, t-tests, and Bland-Altman plots were used to
      investigate adolescent-parent disagreement. Participant characteristics, illness
      expectations, and illness perceptions influencing adolescent-parent disagreement
      were studied using regression analysis. RESULTS: Seventy adolescent-parent pairs
      were included. There were a moderate correlation (ICC = 0.61, P < 0.001) and no
      significant difference (3.78 vs 3.56, P = 0.103) between adolescent-self-reported
      and parent-proxy-reported HRQL at group level. However, Bland-Altman plots showed
      relevant differences (exceeding the minimal important difference) for 63% of all
      adolescent-parent pairs. Adolescent's age (> 15 years), poorer adolescent
      reported illness comprehension (Brief-IPQ-TF, coherence), and higher adolescent
      reported perceived disease severity (Food Allergy Independent Measure-Teenager
      Form & -Parent Form) were associated with adolescent-parent disagreement.
      CONCLUSIONS: Adolescent-parent disagreement on the adolescent's HRQL was mainly
      associated with adolescents' rather than parents' perceptions and
      characteristics. Illness comprehension of the adolescent may be an important
      target for intervention aimed at reducing adolescent-parent disagreement.

PMID- 21958235
TI  - Suicides during 7 years among a catchment area cohort of patients with psychoses.
AB  - OBJECTIVE: To investigate a series of consecutive suicides at a psychosis clinic
      by using a psychological autopsy technique. METHOD: The clinic serves an adult
      population of 225,000 individuals, of whom 0.5% have regular contact with the
      clinic. During a 71/2-year period, 23 men and nine women committed suicide, which
      corresponds to an odds ratio of 14. RESULTS: Most patients were schizophrenic,
      and 24 were outpatients. Suicide methods were violent in all but two cases.
      Nineteen had a history of at least one suicide attempt, and 24 were known to have
      had suicidal ideation. More than half had no social contacts over the last year
      except with psychiatric staff. The median time between the last contact with the
      psychiatric services and the suicide was 4 days. No warning signs were noted. At
      the time of death, 3 of the 24 who were prescribed antipsychotics, and none of
      the 10 who were prescribed antidepressants had plasma levels of the corresponding
      drug. CONCLUSION: Findings of special interest are the lack of forewarnings and
      the poor drug compliance. Patients appear to have played "business as usual" with
      the care-givers, and did it well. Is it a sign of health and despair, or illness?

PMID- 21958236
TI  - Mapping QTLs for oil traits and eQTLs for oleosin genes in jatropha.
AB  - BACKGROUND: The major fatty acids in seed oil of jatropha, a biofuel crop, are
      palmitic acid (C16:0), stearic acid (C18:0), oleic acid (C18:1) and linoleic acid
      (C18:2). High oleic acid and total oil content are desirable for jatropha
      breeding. Until now, little was known about the genetic bases of these oil traits
      in jatropha. In this study, quantitative trait locus (QTL) and expression QTL
      analyses were applied to identify genetic factors that are relevant to seed oil
      traits in jatropha. RESULTS: Composite interval mapping identified 18 QTL
      underlying the oil traits. A highly significant QTL qC18:1-1 was detected at one
      end of linkage group (LG) 1 with logarithm of the odd (LOD) 18.4 and percentage
      of variance explained (PVE) 36.0%. Interestingly, the QTL qC18:1-1 overlapped
      with qC18:2-1, controlling oleic acid and linoleic acid compositions. Among the
      significant QTL controlling total oil content, qOilC-4 was mapped on LG4 a
      relatively high significant level with LOD 5.0 and PVE 11.1%. Meanwhile, oleosins
      are the major composition in oil body affecting oil traits; we therefore
      developed SNP markers in three oleosin genes OleI, OleII and OleIII, which were
      mapped onto the linkage map. OleI and OleIII were mapped on LG5, closing to QTLs
      controlling oleic acid and stearic acid. We further determined the expressions of
      OleI, OleII and OleIII in mature seeds from the QTL mapping population, and
      detected expression QTLs (eQTLs) of the three genes on LGs 5, 6 and 8
      respectively. The eQTL of OleIII, qOleIII-5, was detected on LG5 with PVE 11.7%
      and overlapped with QTLs controlling stearic acid and oleic acid, implying a cis-
      or trans-element for the OleIII affecting fatty acid compositions. CONCLUSION: We
      identified 18 QTLs underlying the oil traits and 3 eQTLs of the oleosin acid
      genes. The QTLs and eQTLs, especially qC18:1-1, qOilC-4 and qOleIII-5 with
      contribution rates (R2) higher than 10%, controlling oleic acid, total oil
      content and oleosin gene expression respectively, will provide indispensable data
      for initiating molecular breeding to improve seed oil traits in jatropha, the key
      crop for biodiesel production.

PMID- 21958237
TI  - Role of anti-beta1 adrenergic antibodies from patients with periodontitis in
      cardiac dysfunction.
AB  - BACKGROUND: The presence of serum autoantibodies against beta(1) adrenoreceptors
      (beta(1)-ARs) in human gingival fibroblast from patients with periodontitis
      inhibits primary cell-specific growth and induces over-expression of pro
      inflammatory mediators. Serum beta(1)-AR autoantibodies from patients with
      periodontitis react with myocardium and modify cardiac contractility. The
      relationship between the presence of serum beta(1)-AR autoantibodies and
      alterations in heart rate variability (HRV) was also studied. METHODS: An enzyme
      linked immunosorbent assay (ELISA) using cardiac and gingival fibroblast
      membranes or synthetic peptides corresponding to the second extracellular loop of
      human beta(1)-AR was used to detect serum autoantibodies. The HRV was assessed
      from RR interval files generated from 22:00 to 08:00 hours. The autoantibody
      effects on contractility were measured on spontaneous rat isolated atria.
      RESULTS: Circulating autoantibodies from 36 patients with periodontitis and 20
      healthy individuals (controls) interacted with fibroblasts, the cardiac surface,
      and beta(1)-AR synthetic peptides. The distributions of serum antibodies against
      gingival and myocardium membranes and beta(1)-AR synthetic peptide were 88.8%,
      77.7%, and 92.8%, respectively. Moreover, 88.5% of patients with periodontitis
      whose sera were positive against beta(1)-AR synthetic peptide had decreased HRV.
      The corresponding affinity-purified anti-beta(1)-AR peptide IgG displayed partial
      agonist-like activity modifying the isolated atria contractility. CONCLUSION:
      This manuscript describes that patients with periodontitis showed increased
      levels of serum IgG with reactive activity against beta(1)-AR. Those patients
      demonstrated decrease in heart rate, and IgG derived from their sera induced
      aberrant contractility of heart atrium. We propose that periodontitis increases
      the risk of cardiovascular diseases, although it increases anti-beta(1)-AR
      autoantibody that alters myocardial contractility.

PMID- 21958238
TI  - Antibacterial activity of the plant-derived compounds 23-methyl-6-O
      desmethylauricepyrone and (Z,Z)-5-(trideca-4,7-dienyl)resorcinol and their
      synergy with antibiotics against methicillin-susceptible and -resistant
      Staphylococcus aureus.
AB  - The present study investigated the antibacterial activity of two plant-derived
      compounds, 23-methyl-6-O-desmethylauricepyrone (1) and (Z,Z)-5-(trideca-4,7
      dienyl)resorcinol (2), and their synergistic effects with erythromycin and
      gentamicin against methicillin-susceptible (MSSA) and gentamicin- and methicillin
      resistant Staphylococcus aureus (MRSA). Studies of the individual antibacterial
      activity of each plant-derived compound and synergy experiments were carried out,
      by the microdilution test in agar and by the checkerboard method, respectively.
      Compound 1 showed minimum inhibitory concentration (MIC) and minimum bactericidal
      concentration (MBC) values of 2 and 8 MUg/mL, respectively, against both strains
      of S. aureus, while compound 2 exhibited anti-MSSA and anti-MRSA activity with
      MICs and MBCs of 4 and 8 and 2 and 8 MUg/mL, respectively. Time-kill curves
      showed that, while compound 1 produced complete killing of both strains at 24 h
      from the beginning of the experiment, 2 produced the same effect in the first
      hour. Combinations of 1 with erythromycin or gentamicin showed a notable
      synergism against MSSA, which enabled the antibiotic concentration to decrease by
      up to 300 or 260 times, respectively. When the aminoglycoside was placed together
      with compound 2, only an additive effect was observed. The assayed compounds did
      not produce erythrocyte hemolysis or genotoxicity and they did not affect
      macrophage viability at the effective or higher concentrations. These results
      suggest that both compounds could be considered as promising antibacterial agents
      while compound 1 could be used in combinatory therapies with erythromycin and
      gentamicin.

PMID- 21958239
TI  - Distinct In Vitro Myelopoiesis is Dependent on the Self-Renewal of Hematopoietic
      Progenitors.
AB  - Spleen and bone marrow (BM) have been shown to contain the progenitors of a novel
      dendritic-like antigen-presenting cell type (L-DC). These progenitors are also
      maintained in both long-term spleen cultures and co-cultures of spleen or BM over
      the stromal cell line STX3. We examined mouse foetal liver (FL), rich in
      hematopoietic stem/progenitor cells (HSC/HPC) after embryonic day (E) 12.5, for
      the presence of L-DC progenitors by testing their capacity to colonize STX3 and
      produce L-DC. E14.5 FL from wild-type C57BL/6J mice was found to colonize STX3
      and produce L-DC for 28 days. By contrast, E14.5 FL from Ikaros Plastic mice gave
      only short-term production of low numbers of L-DC between 7 and 14 days of co
      culture. The transient and weak production of L-DC by FL from Plastic E14.5 mice
      maps to the loss of self-renewal capacity amongst HSC. L-DC progenitors are,
      therefore, closely aligned with a subset of self-renewing HSC/HPC in FL.

PMID- 21958291
TI  - Reply to "Comment on 'Preparation and characterization of silver-poly(vinylidene
      fluoride) nanocomposites: formation of piezoelectric polymorph of poly(vinylidene
      fluoride)'".

PMID- 21958292
TI  - Synthesis and biochemical evaluation of delta(2)-isoxazoline derivatives as DNA
      methyltransferase 1 inhibitors.
AB  - A series of Delta(2)-isoxazoline constrained analogues of procaine/procainamide
      (7a-k and 8a-k) were prepared and their inhibitory activity against DNA
      methyltransferase 1 (DNMT1) was tested. Among them, derivative 7b is far more
      potent in vitro (IC(50) = 150 MUM) than other non-nucleoside inhibitors and also
      exhibits a strong and dose-dependent antiproliferative effect against HCT116
      human colon carcinoma cells. The binding mode of 7b with the enzyme was also
      investigated by means of a simple competition assay as well as of docking
      simulations conducted using the recently published crystallographic structure of
      human DNMT1. On the basis of the findings, we assessed that the mode of
      inhibition of 7b is consistent with a competition with the cofactor and propose
      it as a novel lead compound for the development of non-nucleoside DNMT
      inhibitors.

PMID- 21958293
TI  - Light-regulated mRNA condensation by a photosensitive surfactant works as a
      series photoswitch of translation activity in the presence of small RNAs.
AB  - AzoTAB, a photosensitive azobenzene cationic surfactant, which phototriggers
      translation activity through light-regulated condensation of mRNA, is added to a
      translation solution containing several mRNAs, which can be selectively silenced
      by specific small RNAs. We find that gene silencing by small RNAs remains
      functional regardless of AzoTAB concentration and UV illumination. In the absence
      of UV, the translation of all genes present in the medium is partially to fully
      inhibited depending on AzoTAB concentration. In contrast, the application of a
      short UV stimulus (365 nm for 1.5 min) results in the selective photoactivation
      of genes that are not silenced by small RNA. These results show that light
      regulated condensation by AzoTAB works as a sequence-independent series
      photoswitch added to parallel sequence-specific regulation by small RNAs.

PMID- 21958295
TI  - Hearing loss in adults surviving pneumococcal meningitis is associated with
      otitis and pneumococcal serotype.
AB  - We assessed the incidence of hearing loss and its relationship with clinical
      characteristics and pneumococcal serotypes in adults surviving pneumococcal
      meningitis. We analysed hearing loss in 531 adults surviving pneumococcal
      meningitis included in two prospective nationwide cohort studies performed from
      April 1998 through to October 2002 and March 2006 through to January 2009.
      Hearing loss was evaluated on admission and discharge for all patients. Severe
      hearing loss was assessed by pure tone average on audiology and corrected for
      age, or by the combination of hearing loss on discharge and a score on the
      Glasgow Outcome Scale below 5, which could not be explained by other neurological
      sequelae. A total of 531 episodes of pneumococcal meningitis with non-lethal
      outcome were included. Predisposing conditions for pneumococcal meningitis were
      present in the majority of patients (64%), most commonly otitis (36%). Hearing
      loss was present at discharge in 116 patients (22%) and was classified as mild in
      53% and severe in 47%. Hearing loss was related to otitis (odds ratio [OR], 2.58;
      95% confidence interval [CI], 1.66-4.02; p < 0.001) and inversely related to
      serotype 23 F infection (OR, 0.36; 95% CI, 0.13-0.98; p = 0.025), but not with
      parameters of disease severity or indicators of cerebrospinal fluid inflammation
      severity. Meningitis due to pneumococcal serotype 3 was associated with the
      highest rate of hearing loss. Hearing loss frequently complicates pneumococcal
      meningitis. Risk factors for hearing loss were infection with pneumococcal
      serotype 23 F and otitis, but not disease severity. Otitis and resulting
      perilympathic inflammation contribute to meningitis-associated hearing loss.

PMID- 21958294
TI  - T-cell receptor gene therapy in human melanoma-bearing immune-deficient mice:
      human but not mouse T cells recapitulate outcome of clinical studies.
AB  - Adoptive cell therapy using T-cell receptor (TCR)-engineered T cells is a
      clinically feasible and promising approach to target tumors, but is currently
      faced with compromised antitumor efficacies in patients. Here, we extensively
      validated immune-deficient mice to facilitate further development of the
      therapeutic potential of TCR-engineered T cells. Treatment of human melanoma
      bearing SCID or NSG mice with high doses of human T cells transduced with an
      hgp100/HLA-A2-specific TCR did not result in antitumor responses irrespective of
      chemotherapeutic preconditioning. Imaging of human green fluorescent protein
      labeled T cells demonstrated significant T-cell accumulation in intratumoral
      vasculature directly upon T-cell transfer, which was followed by loss of T cells
      within 72 hr. Peripheral persistence of human T cells was highly compromised and
      appeared related to T-cell differentiation. On the contrary, adoptive transfer
      (AT) of relatively low numbers of hgp100/HLA-A2 TCR-transduced mouse T cells
      resulted in rapid clearance of large established human melanomas. Unexpectedly
      and in contrast to reported studies with chimeric antibody receptor-engineered T
      cells, antitumor activity and homeostatic expansion of T cells were independent
      of TCR transgene as evidenced in two SCID strains and using two different human
      melanoma cell lines. Interestingly, the xeno-reactive melanoma response of mouse
      T cells appeared to be dictated by CD4(+) tumor-infiltrating lymphocytes and did
      not require in vitro T-cell activation, retroviral gene transfer, or subcutaneous
      interleukin-2 support. Taken together, AT of human but not mouse T cells in human
      melanoma-bearing immune-deficient mice is in close accordance with clinical
      studies.

PMID- 21958299
TI  - A cell-cell communication system regulates protease production during sporulation
      in bacteria of the Bacillus cereus group.
AB  - In sporulating Bacillus, major processes like virulence gene expression and
      sporulation are regulated by communication systems involving signalling peptides
      and regulators of the RNPP family. We investigated the role of one such
      regulator, NprR, in bacteria of the Bacillus cereus group. We show that NprR is a
      transcriptional regulator whose activity depends on the NprX signalling peptide.
      In association with NprX, NprR activates the transcription of an extracellular
      protease gene (nprA) during the first stage of the sporulation process. The
      transcription start site of the nprA gene has been identified and the minimal
      region necessary for full activation has been characterized by promoter
      mutagenesis. We demonstrate that the NprX peptide is secreted, processed and then
      reimported within the bacterial cell. Once inside the cell, the mature form of
      NprX, presumably the SKPDIVG heptapeptide, directly binds to NprR allowing nprA
      transcription. Alignment of available NprR sequences from different species of
      the B. cereus group defines seven NprR clusters associated with seven NprX
      heptapeptide classes. This cell-cell communication system was found to be strain
      specific with a possible cross-talk between some pherotypes. The phylogenic
      relationship between NprR and NprX suggests a coevolution of the regulatory
      protein and its signalling peptide.

PMID- 21958300
TI  - Testes size, testosterone production and reproductive behaviour in a natural
      mammalian mating system.
AB  - 1. Testosterone (T) is a key mediator in the expression of numerous morphological
      and behavioural traits in mammals, but the factors underlying individual
      variation in circulating T levels are poorly understood. 2. The intimate
      structural integration of sperm and T production within the testes, alongside the
      dependency of sperm production on high levels of T, suggests that T requirements
      for spermatogenesis could be an important driver of individual differences in T.
      3. To test this hypothesis, we examine how male capacity for sperm production (as
      indicated by their testes size) is associated with T levels in a feral population
      of Soay sheep, resident on St. Kilda, Scotland, during their rutting season. 4.
      We found a strong positive relationship between an individual's testes size (as
      measured before their seasonal enlargement) and the levels of circulating T
      during their rut, suggesting that T requirements for spermatogenesis has a
      prominent influence on the production of this androgen. 5. In contrast, body
      condition and competitive ability did not independently predict T levels,
      findings that are inconsistent with conventional 'condition-dependent' and
      'challenge' hypotheses of T production. 6. This influence of male's capacity for
      sperm production on T appeared to be substantial enough to be biologically
      relevant, as testes size also predicted male aggression and mate-seeking
      behaviour. 7. Our results suggest that a male's inherent capacity for sperm and T
      production is tightly phenotypically integrated, with potential consequences for
      a wide range of other T-mediated reproductive traits.

PMID- 21958301
TI  - Pulsed electromagnetic fields stimulation prevents steroid-induced osteonecrosis
      in rats.
AB  - BACKGROUND: Pulsed electromagnetic fields (PEMF) stimulation has been used
      successfully to treat nonunion fractures and femoral head osteonecrosis, but
      relatively little is known about its effects on preventing steroid-induced
      osteonecrosis. The purpose of the study was to investigate the effects of PEMF
      stimulation on the prevention of steroid-induced osteonecrosis in rats and
      explore the underlying mechanisms. METHODS: Seventy-two male adult Wistar rats
      were divided into three groups and treated as follows. (1) PEMF stimulation group
      (PEMF group, n = 24): intravenously injected with lipopolysaccharide (LPS, 10
      MUg/kg) on day 0 and intramuscularly injected with methylprednisolone acetate
      (MPSL, 20 mg/kg) on days 1, 2 and 3, then subjected to PEMF stimulation 4 h per
      day for 1 to 8 weeks. (2) Methylprednisolone-treated group (MPSL group, n = 24):
      injected the same dose of LPS and MPSL as the PEMF group but without exposure to
      PEMF. (3) Control group (PS group, n = 24): injected 0.9% saline in the same mode
      at the same time points. The incidence of osteonecrosis, serum lipid levels and
      the mRNA and protein expression of transforming growth factor beta1 (TGF-beta1)
      in the proximal femur were measured 1, 2, 4 and 8 weeks after the last MPSL (or
      saline) injection. RESULTS: The incidence of osteonecrosis in the PEMF group
      (29%) was significantly lower than that observed in the MPSL group (75%), while
      no osteonecrosis was observed in the PS group. The serum lipid levels were
      significantly lower in the PEMF and PS groups than in the MPSL group. Compared
      with the MPSL and PS groups, the mRNA expression of TGF-beta1 increased, reaching
      a peak 1 week after PEMF treatment, and remained high for 4 weeks, then declined
      at 8 weeks, whereas the protein expression of TGF-beta1 increased, reaching a
      peak at 2 weeks after PEMF treatment, and remained high for 8 weeks. CONCLUSIONS:
      PEMF stimulation can prevent steroid-induced osteonecrosis in rats, and the
      underlying mechanisms involve decreased serum lipid levels and increased
      expression of TGF-beta1.

PMID- 21958302
TI  - Treatment of refractory pain with botulinum toxins--an evidence-based review.
AB  - OBJECTIVES: To provide updated information on the role of botulinum toxins in the
      treatment of refractory pain based on prospective, randomized, double-blind,
      placebo-controlled studies. DESIGN OF THE REVIEW: Class I and class II articles
      were searched online through PubMed (1966 to the end of January 2011) and OvidSP
      including ahead-of-print manuscripts. RESULTS: Level A evidence (two or more
      class I studies-established efficacy): pain of cervical dystonia, chronic
      migraine, and chronic lateral epicondylitis. Level B evidence (one class I or two
      class II studies-probably effective and recommended): post-herpetic neuralgia,
      post-traumatic neuralgia, pain of plantar fasciitis, piriformis syndrome, and
      pain in total knee arthroplasty. Level C evidence (one class II study-possibly
      effective, may be used at discretion of clinician): allodynia of diabetic
      neuropathy, chronic low back pain, painful knee osteoarthritis, anterior knee
      pain with vastus lateralis imbalance, pelvic pain, post-operative pain in
      children with cerebral palsy after adductor hip release surgery, post-operative
      pain after mastectomy, and sphincter spasms and pain after hemorrhoidectomy.
      Level U evidence (efficacy not proven due to diverse class I and II results):
      myofascial pain syndrome and chronic daily headaches. Studies in episodic
      migraine and tension headaches have shown treatment failure (level A-negative).
      CONCLUSION: Evidence-based data indicate that administration of botulinum toxin
      in several human conditions can alleviate refractory pain. The problems with some
      study designs and toxin dosage are critically reviewed.

PMID- 21958303
TI  - Hitting the dartboard from 40,000 feet: a better chance with your eyes open!

PMID- 21958305
TI  - Single-port access adrenalectomy: our initial experience.
AB  - BACKGROUND: After being introduced in 1992, laparoscopic adrenalectomy has been
      accepted as the gold standard today for benign diseases. The need is now being
      realized for newer innovations to further reduce the trauma of surgical access.
      We report our experience and outcome of the first case series of single-port
      access adrenalectomy by using SILSTM port. METHODS: Between June 2009 and
      November 2010, 6 patients with adrenal tumors underwent single-port access
      adrenalectomy via SILS port. The device was placed through a single 3 cm
      incision. The patients' demographics, adrenal mass characteristics, operative
      time, conversion rate, intraoperative and postoperative complications, and
      postoperative pain score were measured. Five patients underwent adrenalectomy by
      using the retroperitoneal approach and 1 by using the laparoscopic
      transperitoneal approach. RESULTS: Three men and 3 women with mean age 51 years
      (range, 37-67) underwent single-incision adrenalectomy. The mean tumor size was
      3.3 cm (range, 1.5-6). Three of these cases were Conn's syndrome, and the
      remaining 3 were incidentaloma. No significant complications or conversions to
      the conventional procedure were recorded. The mean operative time was 121 minutes
      (range, 70-165). The mean hospital stay was 2.7 days (range, 2-4). No local
      recurrences or hormonal relapse have been recorded to the present with a median
      follow-up of 12 months (range, 3-20). CONCLUSIONS: In our short experience,
      single-port access adrenalectomy seems to be safe and feasible in improving the
      advantages of laparoscopic approach, especially in terms of cosmesis, but further
      randomized controlled trials are needed to evaluate the benefits of this novel
      approach.

PMID- 21958304
TI  - HBeAg and not genotypes predicts viral load in patients with hepatitis B in
      Denmark: a nationwide cohort study.
AB  - OBJECTIVE: To explore the influence of HBV genotype on viral load in patients
      with HBV infection, and to investigate the relation to gender, age and country of
      origin or antibodies against hepatitis Be antigen (anti-HBe). MATERIALS: We
      investigated 1025 patients with hepatitis B virus infection in a nationwide study
      in Denmark. RESULTS: Prevalence of genotypes were: 10.5% A, 17.3% B, 20.5% C,
      45.7% D, 3.2% E, 0.6% F, 1.1% G and 1% had more than one genotype. Nearly 60% of
      patients with genotype A were from Africa, 82% and 93% with genotypes B or C were
      from East Asia, 62% with genotype D came from the Middle East and 91% with
      genotype E came from Africa. More women had genotypes B (p = 0.006) or C (p <
      0.001) while more men had genotypes A (p = 0.015) or D (p < 0.001). Women with
      genotypes B and D were younger than men (p < 0.001, p = 0.026). Viral load
      differed in genotype A and D compared with B and C (p < 0.001), and between anti
      HBe and hepatitis B e antigen (HBeAg) positive patients (median values 5.4 *
      10(3) IU/ml and 7.4 * 10(7) IU/ml, respectively, p < 0.001). Viral load depended
      on the presence of HBeAg (p < 0.001; OR, 95% CI: 0.05, 0.03-0.07) in the adjusted
      analysis and was not affected by origin (p = 0.65), age (p = 0.12), gender (p =
      0.06) or genotype (p = 0.10). CONCLUSION: HBeAg status and not HBV genotype
      influenced viral load in this nationwide study. HBeAg positive patients had
      median HBV-DNA levels 10,000 times higher than those anti-HBe positive across
      genotypes.

PMID- 21958306
TI  - Cystoscopy-assisted percutaneous removal of impacted urethral stone: a case
      report.
AB  - BACKGROUND AND PURPOSE: Although cystolitholapaxy is possible in children, the
      instruments are not available everywhere. For tiny impacted urethral stone, an
      alternate technique is described. CASE REPORT: A 3-year-old boy came with
      retention of urine and dysuria. On examination: bladder was full, suprapubic
      region was tender, and a stone could be felt at posterior urethra. We planned
      push back and suprapubic cystolithotomy. After general anesthesia, the stone was
      pushed back by instillation of lignocaine jelly into the urethra. Then, a
      cystoscope was introduced, and a stone was found inside the urinary bladder.
      Under cystoscopic view, a 5 mm laparoscopic port was inserted into the bladder
      just above the pubic symphysis in the midline. A 5 mm tissue holding forceps was
      introduced through this port, and the tiny stone was grasped and brought out
      along with the port. The port site was closed by a single stitch. A penile
      catheter was kept for 5 days. RESULTS: The boy did well in the postoperative
      period, and voiding was normal after removal of the catheter. CONCLUSIONS:
      Impacted posterior urethral stone can be retrieved by simple percutaneous
      technique.

PMID- 21958307
TI  - Estimation of the distribution of intravenously injected adipose tissue-derived
      stem cells labeled with quantum dots in mice organs through the determination of
      their metallic components by ICPMS.
AB  - Adipose tissue-derived stem cells (ASCs) have shown promise in cell therapy
      because of their ability to self-renew damaged or diseased organs and easy
      harvest. To ensure the distribution and quantification of the ASCs injected from
      tail vein, several whole-body imaging techniques including fluorescence optical
      imaging with quantum dots (QDs) have been employed, but they may suffer from
      insufficient sensitivity and accuracy. Here, we report quantitative distribution
      of ASCs in various organs (heart, lung, liver, spleen, and kidney) of mice, which
      were intravenously injected with QDs-labeled ASCs (QDs-ASCs), through the
      detection of QDs-derived metallic components by inductively coupled plasma mass
      spectrometry (ICPMS). For accurate and precise determination, each organ was
      harvested and completely digested with a mixture of HNO(3) and H(2)O(2) in a
      microwave oven prior to ICPMS measurement, which was equipped with a microflow
      injection system and a laboratory-made capillary-attached micronebulizer. After
      optimization, 16 elements including major components (Cd, Se, and Te) of QDs and
      essential elements (Na, K, Mg, Ca, P, S, Mn, Fe, Co, Cu, Zn, Se, Sr, and Mo) were
      successfully determined in the organs. As compared to untreated mice, QDs-ASCs
      treated mice showed significantly higher levels of Cd and Te in all organs, and
      as expected, the molar ratio of Cd to Te in each organ was in good agreement with
      the molar composition ratio in the QDs. This result indicates that the increment
      of Cd (or Te) can be used as a tracer for calculating the distribution of ASCs in
      mice organs. As a result of the calculation, 36.8%, 19.1%, 0.59%, 0.49%, and
      0.25% of the total ASCs injected were estimated to be distributed in the liver,
      lung, heart, spleen, and kidney, respectively.

PMID- 21958309
TI  - ortho-Bromo(propa-1,2-dien-1-yl)arenes: substrates for domino reactions.
AB  - o-Bromo(propa-1,2-dien-1-yl)arenes exhibit novel and orthogonal reactivity under
      Pd catalysis in the presence of secondary amines to form enamines (concerted Pd
      insertion, intramolecular carbopalladation, and terminative Buchwald-Hartwig
      coupling) and of amides to form indoles (addition, Buchwald-Hartwig cyclization,
      and loss of the acetyl group). The substrates for these reactions can be accessed
      in a reliable and highly selective two-step process from 2-bromoaryl bromides.

PMID- 21958308
TI  - 100 years of microbial electricity production: three concepts for the future.
AB  - Bioelectrochemical systems (BES) have been explored according to three main
      concepts: to produce energy from organic substrates, to generate products and to
      provide specific environmental services. In this work, by using an engineering
      approach, biological conversion rates are calculated for BES resp. anaerobic
      digestion. These rates are compared with currents produced by chemical batteries
      and chemical fuel cells in order to position BES in the 'energy'-market. To
      evaluate the potential of generating various products, the biochemistry behind
      the biological conversion rates is examined in relation to terminal electron
      transfer molecules. By comparing kinetics rather than thermodynamics, more
      insight is gained in the biological bottlenecks that hamper a BES. The short-term
      future for BES research and its possible application is situated in smart niches
      in sustainable environmental development, i.e. in processes where no large
      currents or investment cost intensive reactors are needed to obtain the desired
      results. Some specific examples are identified.

PMID- 21958310
TI  - Luminescent Ir(III) complex exclusively made of polypyridine ligands capable of
      intercalating into calf-thymus DNA.
AB  - Efficient intercalation of a luminescent Ir(III) complex exclusively made of
      polypyridine ligands in natural and synthetic biopolymers is reported for the
      first time. The emission of the complex is largely enhanced in the presence of
      [poly(dA-dT)(2)] and strongly quenched in the presence of [poly(dG-dC)(2)]. By
      comparing the emission decays in DNA and in synthetic polynucleotides, it is
      proposed that the emission quenching of the title compound by guanine residues in
      DNA is no longer effective over a distance of four dA-dT base pairs.

PMID- 21958312
TI  - Bisphosphonates-related osteonecrosis of the jaws: a concise review of the
      literature and a report of a single-centre experience with 151 patients.
AB  - The osteonecrosis of the jaws (ONJ) is an adverse side effect of long-term
      bisphosphonate therapy (BPT) firstly described in 2003. The aetiology of BRONJ
      remains unknown, and the pathogenesis seems multifactorial and related to several
      local or general factors. Many expert panel developed preventive protocols to
      facilitate specialists involved in the multidisciplinary management of BRONJ
      patients. In this paper, we present a concise review of the literature, and we
      report the experience of the University of Parma with 151 patients that assumed
      BPT for both oncological (121 patients) and non-oncological (30 patients)
      diseases. One hundred and thirty-nine BRONJ sites were treated with different
      approaches (surgical and non-surgical, laser-assisted and non-laser-assisted): in
      terms of clinical improvement, a statistically significant difference was found
      between the group treated with the only medical therapy; in terms of complete
      healing, the introduction in the treatment protocols of both laser-assisted
      approach and surgical approach improves the therapeutical results.

PMID- 21958311
TI  - Mizoribine provides effective treatment of sequential histological change of
      arteritis and reduction of inflammatory cytokines and chemokines in an animal
      model of Kawasaki disease.
AB  - The incidence of panvasculitis in the coronary arteries and aortic root was 100%
      in the control group. The incidence of panvasculitis in the MZR group decreased
      to 50%. Moreover, the scope and severity of the inflammation of those sites were
      significantly reduced in the MZR group as well as the IgG group. On the other
      hand, increased cytokines and chemokines, such as IL-1alpha, TNF-alpha, KC, MIP
      1alpha, GM-CSF, and IL-13, in the nontreatment group were significantly
      suppressed by treatment with MZR, but the MCP-1 level increased. In addition, IL
      1alpha, TNF-alpha, IL-10, IL-13, and MIP-1alpha were suppressed by treatment in
      the IgG group. BACKGROUND: Intravenous immunoglobulin (IVIg) treatment results in
      an effective response from patients with acute-phase Kawasaki disease (KD), but
      16.5% of them remain nonresponsive to IVIg. To address this therapeutic
      challenge, we tried a new therapeutic drug, mizoribine (MZR), in a mouse model of
      KD, which we have established using injections of Candida albicans water-soluble
      fractions (CAWS). METHODS: CAWS (4 mg/mouse) were injected intraperitoneally into
      C57BL/6N mice for 5 consecutive days. MZR or IgG was administered for 5 days.
      After 4 weeks, the mice were sacrificed and autopsied, the hearts were fixed in
      10% neutral formalin, and plasma was taken to measure cytokines and chemokines
      using the Bio-Plex system. RESULTS: The incidence of panvasculitis in the
      coronary arteries and aortic root was 100% in the control group. The incidence of
      panvasculitis in the MZR group decreased to 50%. Moreover, the scope and severity
      of the inflammation of those sites were significantly reduced in the MZR group as
      well as the IgG group. On the other hand, increased cytokines and chemokines,
      such as IL-1alpha TNF-alpha, KC, MIP-1alpha, GM-CSF, and IL-13, in the
      nontreatment group were significantly suppressed by treatment with MZR, but the
      MCP-1 level increased. In addition, IL-1alpha, TNF-alpha, IL-10, IL-13, and MIP
      1alpha were suppressed by treatment in the IgG group. CONCLUSION: MZR treatment
      suppressed not only the incidence, range, and degree of vasculitis, but also
      inflammatory cytokines and chemokines in the plasma of the KD vasculitis model
      mice, suggesting that MZR may be useful for treatment of KD.

PMID- 21958313
TI  - Prescription rates of ADHD medication in the Scandinavian countries and their
      national guidelines.

PMID- 21958315
TI  - Synthesis and herbicidal activity of diphenyl ether derivatives containing
      unsaturated carboxylates.
AB  - A series of novel diphenyl ether derivatives containing unsaturated carboxylates
      were designed and synthesized. Their structures were identified by (1)H nuclear
      magnetic resonance and elemental analyses. The bioassays indicated that the
      compounds 5b and 5c exhibited good herbicidal activities against velvetleaf at a
      concentration of 30-40 g/hm(2). The relationship between structure and herbicidal
      activity was also discussed. Among unsaturated carboxylates group, butenoate is
      the most promising one. Amonst them, 4-ethoxy-4-oxobutenyl 5-(2-chloro-4
      (trifluoromethyl)phenoxy)-2-nitrobenzoate 5b was identified as the most promising
      candidate due to its high protoporphyrinogen IX oxidase inhibition effect (pI(50)
      = 6.64) and good herbicidal activity against broadleaf weeds with selectivity to
      soybean and low toxicity to mammals.

PMID- 21958314
TI  - Structure-guided design of a methyl donor cofactor that controls a viral histone
      H3 lysine 27 methyltransferase activity.
AB  - vSET (a viral SET domain protein) is an attractive polycomb repressive complex 2
      (PRC2) surrogate to study the effect of histone H3 lysine 27 (H3K27) methylation
      on gene transcription, as both catalyze histone H3K27 trimethylation. To control
      the enzymatic activity of vSET in vivo with an engineered S-adenosyl-l-methionine
      (SAM) analogue as methyl donor cofactor, we have carried out structure-guided
      design, synthesis, and characterization of orthogonal vSET methyltransferase
      mutant/SAM analogue pairs using a "bump-and-hole" strategy.

PMID- 21958316
TI  - Early memories, object relations, and current relationship functioning.
AB  - This study examined the relationship between dependency themes in 140 inpatients'
      early childhood memories (EM) and social interactions involving dependent
      behavior. Hierarchical regression analyses revealed that the type of dependent EM
      predicted overt behavior above and beyond demographic and diagnostic categories.
      Patients expressing clinging dependent themes in their narratives had greater
      involvement in social activities in the therapeutic community program and with
      nurses, whereas patients expressing counterdependent themes engaged in more
      hostile interactions with nursing staff members, were more self-destructive, and
      had more emergency department admissions over the course of inpatient treatment.
      Results are considered in light of the clinical utility of EMs.

PMID- 21958317
TI  - Exploratory study of the relations between sadistic traits and suicidality in a
      nonclinical sample of adolescents.
AB  - The present study explored the relations between sadistic traits and suicidality
      in nonclinical adolescents. Participants were 615 high-school students who
      completed self-report questionnaires. Hierarchical multiple regression analyses
      showed that self-reported sadistic traits explained unique variance in self
      reported suicidality among both genders. This result is confronted with the
      psychodynamic hypothesis linking sadism turned inward and suicidality.

PMID- 21958318
TI  - An exploration of the role of defensive psychopathology in adolescent suicidal
      ideation and behavior.
AB  - The aim of the authors' study was to explore a model of suicidal ideation among
      adolescents in which environmental risk factors were mediated by both depression
      and defensive psychopathology. Suicidal ideation, depression, defensive
      psychopathology (substance use, borderline traits or symptoms, dissociative
      symptoms), parental attachment, and stressful life events were assessed among 615
      adolescents (62% male). Despite gender differences, the proposed model received
      support. Findings suggest a psychodynamic relationship linking suicidal ideation
      to defensive mechanisms, aiming to alleviate depressive affects.

PMID- 21958319
TI  - Changing the name of dementia during residency training: from medication
      management to CBT to psychodynamic psychotherapy.
AB  - In a psychiatry residency outpatient clinic, an elderly woman with dementia and
      depression is successively treated with medication management, cognitive
      behavioral therapy, and psychodynamic psychotherapy. In the course of the
      treatment, the patient and her therapist struggle with what she can hope for as
      her dementia progresses. The use of a transference-based psychotherapy deepens
      and complicates the interactions between patient and therapist, challenging the
      hopes of patient and therapist alike.

PMID- 21958321
TI  - Lentiviral-mediated integrin alpha5 expression in human adult mesenchymal stromal
      cells promotes bone repair in mouse cranial and long-bone defects.
AB  - Abstract   Adult human mesenchymal stromal cells (hMSCs) are an important source
      for tissue repair in regenerative medicine. Notably, targeted gene therapy in
      hMSCs to promote osteogenic differentiation may help in the development of novel
      therapeutic approaches for bone repair. We recently showed that alpha5 integrin
      (ITGA5) promotes osteoblast differentiation in bone marrow-derived hMSCs. Here,
      we determined whether lentiviral (LV)-mediated expression of ITGA5 in hMSCs
      derived from the bone-marrow stroma of healthy individuals may promote bone
      repair in vivo in two relevant critical-size bone defects in the mouse. In a
      first series of experiments, control or LV-ITGA5-transduced hMSCs were seeded on
      collagen-based gelatin sponge and transplanted in a cranial critical-size defect
      (5 mm) in Nude-Foxn1nu mice. Microcomputed tomography and quantitative
      histological analyses after 8 weeks showed no or little de novo bone formation in
      defects implanted with collagen sponge alone or with hMSCs, respectively. In
      contrast, implantation of collagen sponge with LV-ITGA5-transduced hMSCs showed
      greater bone formation compared with control hMSCs. We also tested the bone
      repair potential of LV-mediated ITGA5 expression in hMSCs in a critical-size long
      bone defect (2 mm) in femur in Nude-Foxn1nu mice. Bone remnants were stabilized
      with external fixation, and control or LV-ITGA5-transduced hMSCs mixed with
      coral/hydroxyapatite particles were transplanted into the critical-size long-bone
      defect. Histological analysis after 8 weeks showed that LV-ITGA5-transduced hMSCs
      implanted with particles induced 85% bone regeneration and repair. These results
      demonstrate that repair of critical-size mouse cranial and long-bone defects can
      be induced using LV-mediated ITGA5 gene expression in hMSCs, which provides a
      novel gene therapy for bone regeneration.

PMID- 21958322
TI  - A role for the weak DnaA binding sites in bacterial replication origins.
AB  - DnaA initiates the chromosomal DNA replication in nearly all bacteria, and
      replication origins are characterized by binding sites for the DnaA protein (DnaA
      boxes) along with an 'AT-rich' region. However, great variation in number,
      spatial organization and specificity of DnaA-boxes is observed between species.
      In the study by Taylor et al. (2011), new and unexpectedly weak DnaA-boxes were
      identified within the Caulobacter crescentus origin of replication (Cori). The
      position of weak and stronger DnaA-boxes follows a pattern seen in Escherichia
      coli oriC. This raises the possibility that bacterial origins might be more alike
      than previously thought.

PMID- 21958323
TI  - Prevention and treatment of DNA vaccine encoding cockroach allergen Bla g 1 in a
      mouse model of allergic airway inflammation.
AB  - BACKGROUND: One-fourth of the US population is sensitized to the German
      cockroach. Primary German cockroach allergen Bla g 1 is detected in 63% of homes
      and 52% of childcare facilities in the United States. No effective treatment or
      vaccination strategies are yet available. OBJECTIVES: We evaluated the
      prophylactic and therapeutic efficacy of a plasmid DNA-mediated vaccination using
      the Bla g 1 gene in a mouse model of allergic inflammatory airway disease.
      METHODS: A plasmid DNA vector coding for the Bla g 1 allergen controlled by
      cytomegalovirus promoter was constructed. To estimate the protective efficacy,
      BALB/c mice were given three injections of plasmid DNA-Bla g 1 prior to
      sensitization with two priming doses of recombinant Bla g 1 (rBla g 1) antigens,
      followed by nebulized rBla g 1 challenge. In the therapeutic approach,
      sensitization was followed by administering Bla g 1 DNA vaccine. RESULTS: Bla g 1
      vaccination significantly reduced allergen-induced airway inflammation, even
      after mice were presensitized and a Th2-dominant response was established. The
      Bla g 1 vaccination significantly reduced total inflammatory cell infiltrate,
      eosinophilia, secretion of Th2 cytokines IL-4 and IL-5 in bronchoalveolar lavage
      fluid, allergen-induced inflammatory infiltrates in the lungs, and Bla g 1
      specific IgE in serum upon challenge with rBla g 1. Importantly, Bla g 1 DNA
      vaccination was able to induce IL-10-secreting regulatory T cells that could
      suppress the allergen-specific Th2 cells. CONCLUSION: DNA vaccination showed
      protective and therapeutic efficacy against a clinically relevant allergen Bla g
      1.

PMID- 21958324
TI  - Molecular Diagnostic Challenges and Complex Management of Consecutive Twin
      Pregnancies in a Family with CD40 Ligand Deficiency.
AB  - X-linked hyper-IgM syndrome (XHIGM) is a primary immunodeficiency disorder (PID)
      caused by mutation in the gene encoding the CD40 ligand (CD40L) expressed on
      activated T cells. Prenatal genotyping in carriers with twin pregnancies is more
      challenging than in women with singleton pregnancies. In addition, women with
      twin pregnancies may decide on selective termination for which the risk of loss
      of the healthy foetus may exceed 7%. We report here on a family affected by
      XHIGM. Diagnosis of the disease was made in a male patient as late as 33 years of
      age. After family screening, the sister of the proband conceived male twins in
      two consecutive pregnancies. In the first pregnancy, one of the male foetuses was
      hemizygous for the c.521A>G (Q174R) mutation in the CD40L gene. In the second
      pregnancy, ultrasound scan showed one foetus to have exencephaly and karyotyping
      revealed this foetus to have trisomy 18. Several options were discussed, but the
      parents decided on selective termination in both pregnancies. The interventions
      were successful in both cases, and the mother now has two healthy sons. This
      report demonstrates the way in which advanced technologies in molecular medicine
      and obstetric interventions may assist families with decisions about possible
      selective termination in case of life-threatening molecular or chromosomal
      disorders. Diagnosis of CD40L deficiency at the age of 33 years in the proband
      was striking and indicated that PIDs are still neglected as disease entities in
      the evaluation of patients with recurrent severe infectious diseases.

PMID- 21958325
TI  - Epidemiologic survey of patients with congenital central hypoventilation syndrome
      in Japan.
AB  - BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is a rare disease
      characterized by hypoventilation during sleep. This study discusses the first
      epidemiologic survey of patients with CCHS in Japan. METHODS: The first survey
      was conducted between September and December 2006 and involved 507 registered
      institutes for pediatric training in Japan. The second survey was conducted
      between January and April 2007 and involved only those institutes that confirmed
      diagnosis of CCHS in the first survey or reported on CCHS at a conference during
      the preceding decade. RESULTS: Thirty-seven patients with CCHS were reported from
      23 hospitals. Patient characteristics were as follows: 18 were male, 19 were
      female; and age range 4 months to 34 years. Diagnosis was based on clinical
      symptoms in 37/37 patients; blood gas analysis in 25/37; ventilatory response to
      inhaled CO(2) in 14/37; and genetic analysis (paired-like homeobox gene 2B) in
      11/37. Complications included Hirschsprung's disease in 13/37 and central nervous
      system disorders in 15/37. Prognoses were as follows: 3/37 died in hospital, 1/37
      remained in hospital, 33/37 were on home mechanical ventilation (died 4/33,
      survived 29/33), and 0/37 were cured. Ventilation methods included tracheostomy
      (21/37), use of a nasal mask (9/37), use of a facemask (5/37), and diaphragmatic
      pacing (1/37). CONCLUSIONS: There is currently no consensus on the most
      appropriate methods for diagnosing and treating patients with CCHS in Japan. More
      CCHS-related data need to be collected in the near future in order to enable
      appropriate diagnosis and management of patients with CCHS.

PMID- 21958326
TI  - B-type natriuretic peptide and high sensitive C-reactive protein predict 2-year
      all cause mortality in chest pain patients: a prospective observational study
      from Salta, Argentina.
AB  - BACKGROUND: Several mechanisms are involved in the pathophysiology of the Acute
      Coronary Syndrome (ACS). We have addressed whether B-type natriuretic peptide
      (BNP) and high-sensitive C-reactive protein (hsCRP) in admission samples may
      improve risk stratification in chest pain patients with suspected ACS. METHODS:
      We included 982 patients consecutively admitted with chest pain and suspected ACS
      at nine hospitals in Salta, Northern Argentina. Total and cardiac mortality were
      recorded during a 2-year follow up period. Patients were divided into quartiles
      according to BNP and hsCRP levels, respectively, and inter quartile differences
      in mortality were statistically evaluated applying univariate and multivariate
      analyses. RESULTS: 119 patients died, and the BNP and hsCRP levels were
      significantly higher among these patients than in survivors. In a multivariable
      Cox regression model for total death and cardiac death in all patients, the
      hazard ratio (HR) in the highest quartile (Q4) as compared to the lowest quartile
      (Q1) of BNP was 2.32 (95% confidence interval (CI), 1.24-4.35), p = 0.009 and
      3.34 (95% CI, 1.26-8.85), p = 0.015, respectively. In the TnT positive patients
      (TnT > 0.01 ng/mL), the HR for total death and cardiac death in Q4 as compared to
      Q1 was 2.12 (95% CI, 1.07-4.18), p = 0.031 and 3.42 (95% CI, 1.13-10.32), p =
      0.029, respectively.The HR for total death for hsCRP in Q4 as compared to Q1 was
      1.97 (95% CI, 1.17-3.32), p = 0.011, but this biomarker did not predict cardiac
      death (p = 0.21). No prognostic impact of these two biomarkers was found in the
      TnT negative patients. CONCLUSION: BNP and hsCRP may act as clinically useful
      biomarkers when obtained at admission in a population with suspected ACS.

PMID- 21958327
TI  - MoS2 nanoplates consisting of disordered graphene-like layers for high rate
      lithium battery anode materials.
AB  - MoS(2) nanoplates, consisting of disordered graphene-like layers, with a
      thickness of ~30 nm were prepared by a simple, scalable, one-pot reaction using
      Mo(CO)(6) and S in an autoclave. The product has a interlayer distance of 0.69
      nm, which is much larger than its bulk counterpart (0.62 nm). This expanded
      interlater distance and disordered graphene-like morphology led to an excellent
      rate capability even at a 50C (53.1 A/g) rate, showing a reversible capacity of
      700 mAh/g. In addition, a full cell (LiCoO(2)/MoS(2)) test result also
      demonstrates excellent capacity retention up to 60 cycles.

PMID- 21958328
TI  - In vitro time-dependent vancomycin-resistant Staphylococcus aureus-induced free
      radical generation and status of antioxidant enzymes in murine peritoneal
      macrophage.
AB  - Staphylococcus aureus is most frequently isolated pathogen causing bloodstream
      infections, skin and soft tissue infections, and pneumonia. The immune cells use
      reactive oxygen species (ROS) for carrying out their normal functions, while an
      excess amount of ROS can attack cellular components that lead to cell damage. The
      aim of the present study was to evaluate the free radical generation and status
      of the antioxidant enzymes in murine peritoneal macrophage during in vitro
      vancomycin-resistant S. aureus (VRSA) treatment with different time intervals.
      Peritoneal macrophages were treated with 5 * 10(6) colony-forming units (CFU)/mL
      VRSA cell suspension in vitro for different time intervals (1, 2, 3, 6, 12, and
      24 h), and superoxide anion generation, nicotinamide adenine dinucleotide
      phosphate (NADPH) oxidase activity, myeloperoxidase (MPO) activity, nitric oxide
      (NO) generation, antioxidant enzyme status, and components of glutathione cycle
      were analyzed. Superoxide anion generation, NADPH oxidase activity, MPO activity,
      and NO generation got peak at 3 h indicates maximum free radical generation
      through activation of NADPH oxidase in murine peritoneal macrophages during VRSA
      infection. Reduced glutathione level, glutathione peroxidase, glutathione
      reductase, and glutathione S-transferase activity were decreased significantly (P
      < 0.05) with increasing time of VRSA infection. But the oxidized glutathione
      level was time-dependently increased significantly (P < 0.05) in murine
      peritoneal macrophages. All the changes in peritoneal macrophages after 3 h in
      vitro VRSA treatment had no significant difference. From this study, it may be
      summarized that in vitro VRSA infection not only generates excess free radical
      but also affects the antioxidant status and glutathione cycle in murine
      peritoneal macrophages.

PMID- 21958329
TI  - Structural etiology of chronic low back pain due to motor vehicle collision.
AB  - OBJECTIVE: To estimate prevalence rates of discogenic, facet, and sacroiliac
      joint pain, and describe clinical features of chronic low back pain patients
      whose symptoms were initiated by motor vehicle collisions. DESIGN: Retrospective
      chart review. SETTING: Academic spine center. PATIENTS: Twenty-seven motor
      vehicle collision-induced chronic low back pain patients were included after
      undergoing diagnostic procedures. INTERVENTIONS: Lumbar provocation discography,
      dual diagnostic facet joint blocks, and intra-articular sacroiliac joint
      injections. METHODS: Enrolled patients underwent diagnostic procedures based on
      clinical presentation until the pain source was identified. The prevalence of
      each source of low back pain was estimated. Clinical, categorical, and continuous
      characteristics within the source groups were calculated with SAS v.9.2 (SAS
      Institute Inc., Cary, NC). OUTCOME MEASURES: Etiology and prevalence were
      analyzed for each diagnosis group. RESULTS: Of the 27 patients, 15/27 (56%) were
      diagnosed with discogenic pain, 7/27 (26%) with sacroiliac joint pain, and 5/27
      (19%) with facet joint pain. Seventy-eight percent were female. Mean age was 42.5
      years (standard deviation = 10.4) with median duration of symptoms of 24 months
      (interquartile range = 6-48). CONCLUSIONS: Our study is the first to demonstrate
      that diagnostic spinal injections can identify particular spinal structures,
      namely the intervertebral disc, facet joint, and sacroiliac joint, as the
      specific source of chronic low back pain due to inciting motor vehicle
      collisions. The most common source of motor vehicle collision-induced chronic low
      back pain appears to be the disc followed by the sacroiliac and facet joints.

PMID- 21958330
TI  - Thyroid hormones in children on antiepileptic therapy.
AB  - The aim of this study was to evaluate the thyroid function alterations in a group
      of epileptic children taking antiepileptic drugs (AEDs). Patients demographic
      data and the free throxine (fT4) and thyroid-stimulating hormone (TSH) levels at
      the beginning of the treatment and at the third, sixth and ninth months of AED
      treatment were recorded retrospectively. A total of 106 children, 59 males and 47
      females, were enrolled in the study. Mean patient age was 3.7 years, ranging
      between 3 months and 14 years. In total, 54% of patients were on valproic acid
      (VPA), 16% phenobarbital (PB), 14% were on carbamazepine (CBZ), 6% were on
      oxcarbazepine (OXC), 5% were on levetiracetam, and 5% were on topiramate therapy.
      There were no significant differences in average fT4 values between the drug
      groups. But the mean fT4 levels of the patients on VPA therapy showed a clear
      decrease within the observation period. No significant difference in average TSH
      values between the groups was detected in the beginning and in the third and
      sixth month. However, in the ninth month, a significant increase in TSH values
      was found in the VPA group (p = 0.007). In the patients taking VPA, average TSH
      values rose progressively while staying within normal limits. During follow-up,
      thyroid dysfunction were found in 21 patients (19.6%). A statistically
      significant relationship was found between severe electroencephalography (EEG)
      findings and thyroid dysfunction (p = 0.041). It was concluded that epileptic
      children with severe EEG findings and using VPA could have thyroid dysfunction.
      These patients should be followed up closely by thyroid function tests during
      treatment.

PMID- 21958331
TI  - Life values as predictors of pain, disability and sick leave among Swedish
      registered nurses: a longitudinal study.
AB  - BACKGROUND: Prospective studies on high-risk populations, such as subgroups of
      health care staff, are limited, especially prospective studies among staff not on
      sick-leave. This paper is a report of a longitudinal study conducted to describe
      and compare the importance and consistency of life domains among registered
      nurses (RNs) working in a Swedish hospital and evaluate a model based on the
      consistency of valued life domains for prediction of pain, disability and sick
      leave. METHOD: Importance and consistency ratings of life values, in 9 domains,
      were collected during 2003 and 2006 from 196 RNs using the Valued Living
      Questionnaire (VLQ). Logistic regression analyses were used for prediction of
      pain, disability and sick leave at the three-year follow-up. The predictors
      family relations, marriage couples/intimate relations, parenting, friends/social
      life, work, education, leisure time, psychological well-being, and physical self
      care were used at baseline. RESULTS: RNs rated life values regarding parenting as
      most important and with the highest consistency both at baseline and at follow
      up. No significant differences were found between RNs' ratings of importance and
      consistency over the three-year period, except for friends/social relations that
      revealed a significant decrease in importance at follow-up. The explanatory
      models for pain, disability and sick leave significantly predicted pain and
      disability at follow-up. The odds of having pain were significantly increased by
      one consistency rating (psychological well-being), while the odds were
      significantly decreased by physical self-care. In the model predicting
      disability, consistency in psychological well-being and education significantly
      increased the odds of being disabled, while consistency in physical self-care
      significantly decreased the odds. CONCLUSION: The results suggest that there
      might be a link between intra-individual factors reflecting different aspects of
      appraised life values and musculoskeletal pain (MSP).

PMID- 21958332
TI  - Full-mouth profile of active MMP-8 in periodontitis patients.
AB  - BACKGROUND AND OBJECTIVE: MMP-8 in gingival crevicular fluid is considered as a
      protease with high destructive potential because of its ability to degrade
      collagen in periodontitis-affected patients. The aim of this study was to
      investigate whether there was a relationship between clinical diagnostic
      parameters and the concentration of active MMP-8 (aMMP-8) in gingival crevicular
      fluid in a site-level full-mouth analysis. Based on these data, the prognostic
      value of aMMP-8 levels in relation to pocket depth may be evaluated. MATERIAL AND
      METHODS: Clinical measurements of pocket depth, bleeding on probing (BOP), plaque
      index (PlI) and gingival index (GI), as well as samples of gingival crevicular
      fluid, were obtained from four sites of each tooth of nine healthy female
      patients with chronic generalized periodontitis. The aMMP-8 concentration in
      gingival crevicular fluid was quantified by ELISA using specific monoclonal
      antibodies. Multiple linear regression models for the single measures of aMMP-8
      and pocket depth were calculated with GI and BOP as additional variables.
      RESULTS: Between 92 and 112 recordings were obtained for each parameter in each
      patient. Mean values of between 31.5 and 88.8% were calculated for pocket depths
      of >= 4 mm. Mean pocket depths ranged from 3.11 to 4.73 mm, the mean BOP values
      ranged from 34.0 to 96.7% and the mean full-mouth gingival crevicular fluid aMMP
      8 concentration ranged from 3.2 to 23.7 ng/mL. CONCLUSION: In this sample of
      female periodontitis patients, a broad range of intra-individual and
      interindividual aMMP-8 values was found. Although the explained variance was
      rather weak, a statistically significant relationship between aMMP-8 and pocket
      depth was proven.

PMID- 21958333
TI  - Potential new approaches to modifying intestinal GLP-1 secretion in patients with
      type 2 diabetes mellitus: focus on bile acid sequestrants.
AB  - Type 2 diabetes mellitus is associated with a progressive decline in insulin
      producing pancreatic beta-cells, an increase in hepatic glucose production, and a
      decrease in insulin sensitivity. The incretin hormones glucose-dependent
      insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) stimulate
      glucose-induced insulin secretion; however, in patients with type 2 diabetes, the
      incretin system is impaired by loss of the insulinotropic effects of GIP as well
      as a possible reduction in secretion of GLP-1. Agents that modify GLP-1 secretion
      may have a role in the management of type 2 diabetes. The currently available
      incretin-based therapies, GLP-1 receptor agonists (incretin mimetics) and
      dipeptidyl peptidase-4 (DPP-4) inhibitors (CD26 antigen inhibitors) [incretin
      enhancers], are safe and effective in the treatment of type 2 diabetes. However,
      they may be unable to halt the progression of type 2 diabetes, perhaps because
      they do not increase secretion of endogenous GLP-1. Therapies that directly
      target intestinal L cells to stimulate secretion of endogenous GLP-1 could
      possibly prove more effective than treatment with GLP-1 receptor agonists and DPP
      4 inhibitors. Potential new approaches to modifying intestinal GLP-1 secretion in
      patients with type 2 diabetes include G-protein-coupled receptor (GPCR) agonists,
      alpha-glucosidase inhibitors, peroxisome proliferator-activated receptor (PPAR)
      agonists, metformin, bile acid mimetics and bile acid sequestrants. Both the GPCR
      agonist AR231453 and the novel bile acid mimetic INT-777 have been shown to
      stimulate GLP-1 release, leading to increased insulin secretion and improved
      glucose tolerance in mice. Similarly, a study in insulin-resistant rats
      demonstrated that the bile acid sequestrant colesevelam increased GLP-1 secretion
      and improved glucose levels and insulin resistance. In addition, the bile acid
      sequestrant colestimide (colestilan) has been shown to increase GLP-1 secretion
      and decrease glucose levels in patients with type 2 diabetes; these results
      suggest that the glucose-lowering effects of bile acid sequestrants may be partly
      due to their ability to increase endogenous GLP-1 levels. Evidence suggests that
      GPCR agonists, alpha-glucosidase inhibitors, PPAR agonists, metformin, bile acid
      mimetics and bile acid sequestrants may represent a new approach to management of
      type 2 diabetes via modification of endogenous GLP-1 secretion.

PMID- 21958334
TI  - National survey evaluating service provision for percutaneous endoscopic
      gastrostomy within the UK.
AB  - OBJECTIVES: Percutaneous endoscopic gastrostomy (PEG) feeding has a significant
      morbidity and mortality associated with the procedure. Patient selection,
      procedural volume, timing of insertion and aftercare may have a direct bearing on
      mortality. We aimed to establish whether variation in PEG practice exists within
      the UK. MATERIALS AND METHODS: The British Society of Gastroenterology (BSG)
      approached all NHS hospitals providing an endoscopy service (n = 260). A custom
      designed web-based questionnaire was circulated. RESULTS: The response rate was
      83% (n = 215); 57% were Joint Advisory Group (JAG) accredited; 33% (70/215) of
      hospitals inserted more than 75 PEGs a year (4 hospitals inserting >150). Stroke
      and neurodegenerative conditions were the main indications for PEG insertion.
      However, 36% (77/215) of hospitals inserted PEGs for dementia. PEG insertion
      timings varied: 33% (72/215) had a strict policy of waiting more than 2 weeks
      from referral to insertion, 14% (30/215) performed immediately and 34% (74/215)
      determined the time delay depending on the underlying condition. Local guidelines
      for PEG insertion existed in 87% (186/215) of hospitals and 78% (168/215) had
      access to radiologically inserted gastrostomies. Prophylactic antibiotics were
      used in 93% (201/215) of hospitals. Only 64% (137/215) had a dedicated PEG
      aftercare service. This was significantly lower in non-JAG accredited units (p =
      0.008). CONCLUSION: This National BSG survey demonstrates variations in practice
      particularly with regards to PEG insertion in patients with dementia, the timing
      of PEG insertion and PEG aftercare. These variations in practice may be important
      factors accounting for the significant morbidity and mortality associated with
      this procedure.

PMID- 21958335
TI  - Anti-inflammatory and antimalarial meroterpenoids from the New Zealand ascidian
      Aplidium scabellum.
AB  - Bioassay-directed fractionation of an extract of the New Zealand ascidian
      Aplidium scabellum has afforded the anti-inflammatory secondary metabolite 2
      geranyl-6-methoxy-1,4-hydroquinone-4-sulfate (1) and a family of pseudodimeric
      meroterpenoids scabellones A (2)-D (5). The benzo[c]chromene-7,10-dione scaffold
      contained within scabellones A-D is particularly rare among natural products. The
      structures were elucidated by interpretation of NMR data. Scabellone B was also
      identified as a moderately potent, nontoxic inhibitor of Plasmodium falciparum.

PMID- 21958336
TI  - Synthesis and characterization of the phosphorus triazides OP(N3)3 and SP(N3)3.
AB  - Two explosive triazides of phosphorus(V), OP(N(3))(3) and SP(N(3))(3), have been
      prepared as neat substances and structurally characterized. Both compounds can be
      handled in gas, liquid, and solid states in submillimolar quantities. The melting
      points of OP(N(3))(3) and SP(N(3))(3) are +22 and -30  degrees C, respectively.
      The two triazides have been characterized by IR (Ar matrix and gas phase) and
      Raman (solid) spectroscopies. Their single-crystal structures were obtained by X
      ray diffraction and found to be significantly distorted from the predicted ideal
      C(3) symmetry because of intermolecular interactions. The spectroscopic and
      structural properties are discussed in combination with density functional theory
      calculations.

PMID- 21958337
TI  - Discovery of aminobenzyloxyarylamides as kappa opioid receptor selective
      antagonists: application to preclinical development of a kappa opioid receptor
      antagonist receptor occupancy tracer.
AB  - Arylphenylpyrrolidinylmethylphenoxybenzamides were found to have high affinity
      and selectivity for kappa opioid receptors. On the basis of receptor binding
      assays in Chinese hamster ovary (CHO) cells expressing cloned human opioid
      receptors, (S)-3-fluoro-4-(4-((2-(3-fluorophenyl)pyrrolidin-1
      yl)methyl)phenoxy)benzamide (25) had a K(i) = 0.565 nM for kappa opioid receptor
      binding while having a K(i) = 35.8 nM for MU opioid receptors and a K(i) = 211 nM
      for delta opioid receptor binding. Compound 25 was also a potent antagonist of
      kappa opioid receptors when tested in vitro using a [(35)S]-guanosine 5'O-[3
      thiotriphosphate] ([(35)S]GTP-gamma-S) functional assay in CHO cells expressing
      cloned human opioid receptors. Compounds were also evaluated for potential use as
      receptor occupancy tracers. Tracer evaluation was done in vivo, using liquid
      chromatography-tandem mass spectrometry (LC/MS/MS) methods, precluding the need
      for radiolabeling. (S)-3-Chloro-4-(4-((2-(pyridine-3-yl)pyrrolidin-1
      yl)methyl)phenoxy)benzamide (18) was found to have favorable properties for a
      tracer for receptor occupancy, including good specific versus nonspecific binding
      and good brain uptake.

PMID- 21958339
TI  - Chronic cutaneous leishmaniasis, a great mimicker with various clinical
      presentations: 12 years experience from Aleppo.
AB  - BACKGROUND: Cutaneous leishmaniasis (CL) has been an endemic disease in Aleppo,
      Syria for many decades. During the past 12 years, there was a clear increase in
      the overall incidence of the disease in the region. Treatment using intralesional
      method of antimonial compounds became ineffective in a considerable proportion of
      cases and more patients developed the chronic form of the disease. OBJECTIVES: To
      categorize chronic cutaneous leishmaniasis (CCL) into different subtypes that
      mimic a wide spectrum of skin diseases, and to analyse the cause of this increase
      in the incidence of the disease as a whole and of the chronic type in particular.
      METHODS: A total number of 6200 patients with CL were seen in our centre, among
      which 1880 were initially diagnosed with CCL. Inclusion criteria for CCL included
      CL for more than 1 year. The diagnosis of CCL was made based on the clinical
      presentation and a positive Giemsa smear test. Biopsies were performed whenever
      the Giemsa smear was negative. Patients who had immunosuppression due to a
      medical condition or intake of immunosuppressive medications were excluded.
      RESULTS: Of 1880 patients, 1750 patients fit the inclusion criteria. Based on the
      lesion morphology, three different types of CCL were defined, among which five
      subtypes were observed based on clinical pattern and distribution of lesions. The
      two most common types of CCL were the papulonodular and plaque forms. Around 80%
      of all CCL cases occurred in individuals under 16 years of age and the most
      common location was the face (88.6% of cases). CONCLUSIONS: CCL due to Leishmania
      tropica can mimic many other dermatological conditions which might lead to a
      delay in making the correct diagnosis resulting in increased resistance to
      treatment. We have illustrated eight different clinical presentations of CCL and
      their differential diagnoses to make physicians more aware of the atypical
      presentations of CCL. A new treatment plan is suggested for the high-risk group
      of acute cutaneous leishmaniasis patients to decrease the likelihood of
      progressing to chronicity.

PMID- 21958340
TI  - Enhanced survival of probiotic Lactobacillus acidophilus by encapsulation with
      nanostructured polyelectrolyte layers through layer-by-layer approach.
AB  - The encapsulation of probiotic Lactobacillus acidophilus through layer-by-layer
      self-assembly of polyelectrolytes (PE) chitosan (CHI) and carboxymethyl cellulose
      (CMC) has been investigated to enhance its survival in adverse conditions
      encountered in the GI tract. The survival of encapsulated cells in simulated
      gastric (SGF) and intestinal fluids (SIF) is significant when compared to
      nonencapsulated cells. On sequential exposure to SGF and SIF for 120 min, almost
      complete death of free cells is observed. However, for cells coated with three
      nanolayers of PEs (CHI/CMC/CHI), about 33 log % of the cells (6 log cfu/500 mg)
      survived under the same conditions. The enhanced survival rate of encapsulated L.
      acidophilus can be attributed to the impermeability of polyelectrolyte nanolayers
      to large enzyme molecules like pepsin and pancreatin that cause proteolysis and
      to the stability of the polyelectrolyte nanolayers in gastric and intestinal pH.
      The PE coating also serves to reduce viability losses during freezing and freeze
      drying. About 73 and 92 log % of uncoated and coated cells survived after freeze
      drying, and the losses occurring between freezing and freeze-drying were found to
      be lower for the coated cells.

PMID- 21958338
TI  - Design of therapeutic vaccines: hepatitis B as an example.
AB  - Therapeutic vaccines are currently developed for chronic viral infections, such
      as human papillomavirus (HPV), human immunodeficiency virus (HIV), herpesvirus
      and hepatitis B (HBV) and C (HCV) virus infections. As an alternative to
      antiviral treatment or to support only partially effective therapy a therapeutic
      vaccine shall activate the patient's immune system to fight and finally control
      or ideally even eliminate the virus. Whereas the success of prophylactic
      vaccination is based on rapid neutralization of the invading pathogen by
      antibodies, virus control and elimination of infected cells require T cells.
      Therefore, induction of a multi-specific and multifunctional T-cell response
      against key viral antigens is a paradigm of therapeutic vaccination--besides
      activation of a humoral immune response to limit virus spread. In this review, we
      describe options to develop a therapeutic vaccine for chronic viral infections
      using HBV as a promising example.

PMID- 21958341
TI  - Mobile DNA transposition in somatic cells.
AB  - It had been long assumed that almost all insertions of mobile DNA elements
      occurred during germ-cell development rather than in somatic-cell development,
      but solid evidence for transposition in somatic cells is now accumulating. To add
      to this evidence, a recent paper in Mobile DNA reports the somatic transposition
      of a site-specific retrotransposon, R2, into its insertion site in 28S ribosomal
      DNA in Drosophila embryos.

PMID- 21958343
TI  - A risk-analysis approach to the evaluation of analytical quality.
AB  - BACKGROUND: Setting specifications for analytical quality is always difficult.
      The risk-management approach might be a way to do so. In this approach, the
      definition of the required analytical quality is based on the evaluation of
      patient risk. Risk derives from the probability of error and from the damage that
      such an error might cause. METHODS: Eight Italian laboratories took part in this
      experiment. Measurements of glucose and total calcium were taken as examples.
      Analytical quality was evaluated using a specific ring trial with a frozen serum
      pool and by means of internal quality-control data. The total allowable error was
      defined according to biological variation specifications. The probability of
      error was extracted from the imprecision and comparative bias data of each
      laboratory. The damage caused by a wrong result was evaluated using the absolute
      probability judgment approach. RESULTS: According to the iso-risk plots
      (standardized hyperboles on a graph where the x-axis represents damage and the y
      axis represents probability) for glucose, all the laboratories were working with
      an analytical quality that guaranteed low risk for patients. On the contrary, for
      total calcium none of the laboratories exhibited sufficient quality to guarantee
      low risk for patients, the presence of bias being the most relevant problem.
      CONCLUSIONS: The results seem to demonstrate the applicability of the risk
      approach to the analytical phase, indicating a new possible way to define
      analytical quality targets.

PMID- 21958344
TI  - Reference change values.
AB  - Reference change values (RCV) provide objective tools for assessment of the
      significance of differences in serial results from an individual. The concept is
      simple and the calculation easy, since all laboratories know their analytical
      imprecision (CV(A)) and estimates of within-subject biological variation (CV(I))
      are available for a large number of quantities. Generally, CV(I) are constant
      over time, geography, methodology and in health and chronic stable disease. The
      formula is RCV=2(1/2) . Z . (CV(A)(2) + CV(I)(2))(1/2), where Z is the number of
      standard deviations appropriate to the probability. Correct interpretation of the
      semantics describing the clinical use of RCV is vital for selection of the Z
      score. Many quantities of clinically importance exist for which good estimates of
      RCV are unavailable. Derivation of CV(I) may be difficult for such quantities:
      flair and imagination are required in selecting populations with chronic but
      stable disease on whom CV(I) can be determined. RCV can be used for delta
      checking and auto-verification and laboratory information management systems
      (LIMS) can be adapted to do this. Recently, log-normal transformation to obtain
      unidirectional RCV has been used. Gaps in knowledge of RCV still require filling
      since the need for measures of change is clearly expressed in guidelines.

PMID- 21958345
TI  - Appropriate labelling of blood collection tubes: a step ahead towards patient's
      safety.

PMID- 21958346
TI  - Prevalence, demographics, and health outcomes of comorbid asthma and overweight
      in urban children.
AB  - BACKGROUND: Asthma and overweight are epidemic in urban children but the
      relationship between these conditions is not fully understood. This study
      presents demographic and risk profiles of comorbidity for overweight asthmatic
      children, characterizes morbidity by comparing health outcomes among overweight
      asthmatics and healthy weight asthmatics, and examines socioeconomic factors
      associated with comorbidity. OBJECTIVE: To construct a demographic profile of
      overweight asthmatic children in an urban setting and identify factors that
      contribute to prevalence. METHOD: Cross-sectional study of 5250 children in New
      York City public elementary schools using a parent-report questionnaire on body
      mass index, socioeconomic status, asthma, and asthma-related outcomes. RESULTS:
      Prevalence of overweight (body mass index >= 85th percentile for age and gender)
      was 50.9%. The prevalence of overweight and ever being diagnosed with asthma was
      10.9%. The prevalence of overweight with current asthma was 6.2%. Overweight
      current asthmatics had more night symptoms, missed school days, and asthma
      medication use than healthy weight asthmatics. Almost 50% of overweight current
      asthmatic children reported emergency department visits for asthma compared with
      30% of healthy weight asthmatics. Comorbidity was most prevalent among males,
      Latinos, and children in low-income households, with the highest prevalence among
      Puerto Ricans. In multivariate analysis stratified by gender, the most
      significant factors associated with comorbidity among girls were low income and
      minority race/ethnicity, while among boys significant factors were parental
      education and parental history of asthma. Interestingly, there were few
      underweight children (7.8%) but they had high prevalence of asthma (13.8%).
      CONCLUSIONS: The comorbidity of overweight and asthma has a large impact on urban
      populations, causing greater disease burden than asthma alone. Overweight
      asthmatics show more uncontrolled asthma, evidenced by emergency department
      visits, quick-relief medication use, and days with asthma symptoms. The
      relationship between socioeconomic factors and the asthma-obesity comorbidity may
      vary by gender and requires further study to identify successful interventions to
      reduce disease in children.

PMID- 21958347
TI  - Quantitative analysis of multiple exocyclic DNA adducts in human salivary DNA by
      stable isotope dilution nanoflow liquid chromatography-nanospray ionization
      tandem mass spectrometry.
AB  - Exocyclic DNA adducts, including 1,N(2)-propano-2'-deoxyguanosine derived from
      acrolein (AdG) and crotonaldehyde (CdG) and the three lipid peroxidation-related
      etheno adducts 1,N(6)-etheno-2'-deoxyadenosine (epsilondAdo), 3,N(4)-etheno-2'
      deoxycytidine (epsilondCyt), and 1,N(2)-etheno-2'-deoxyguanosine (1,N(2)
      epsilondGuo), play an important role in cancer formation and they are associated
      with oxidative-stress-induced DNA damage. Saliva is an easily accessible and
      available biological fluid and a potential target of noninvasive biomarkers. In
      this study, a highly sensitive and specific assay based on isotope dilution
      nanoflow LC-nanospray ionization tandem mass spectrometry (nanoLC-NSI/MS/MS) is
      developed for simultaneous detection and quantification of these five adducts in
      human salivary DNA. The levels of AdG, CdG, epsilondAdo, epsilondCyd, and 1,N(2)
      epsilondGuo, measured in 27 human salivary DNA samples from healthy volunteers,
      were determined as 104 +/- 50, 7.6 +/- 12, 99 +/- 50, 72 +/- 49, 391 +/- 198
      (mean +/- SD) in 10(8) normal nucleotides, respectively, starting with 25 MUg of
      DNA isolated from an average of 3 mL of saliva. Statistically significant
      correlations were found between levels of epsilondAdo and epsilondCyd (gamma =
      0.8007, p < 0.0001), between levels of epsilondAdo and 1,N(2)-epsilondGuo (gamma
      = 0.6778, p = 0.0001), between levels of epsilondCyd and 1,N(2)-epsilondGuo
      (gamma = 0.5643, p = 0.0022), between levels of AdG and 1,N(2)-epsilondGuo (gamma
      = 0.5756, p = 0.0017), and between levels of AdG and epsilondAdo (gamma = 0.3969,
      p = 0.0404). Only 5 MUg of DNA sample was analyzed for simultaneous
      quantification of these adducts. The easy accessibility and availability of
      saliva and the requirement for the small amount of DNA samples make this nanoLC
      NSI/MS/MS assay clinically feasible in assessing the possibility of measuring
      1,N(2)-propano-2'-deoxyguanosine and etheno adducts levels in human salivary DNA
      as noninvasive biomarkers for DNA damage resulting from oxidative stress and for
      evaluating their roles in cancer formation and prevention.

PMID- 21958348
TI  - PECC--factor structure and findings in three longitudinal cohorts of patients
      with schizophrenia.
AB  - BACKGROUND: Symptom control by drug treatment is the most important task in
      routine clinical care of patients with schizophrenia. Structured assessment
      methods are needed in this task but not used much. The US-developed Positive and
      Negative Syndrome Scale (PANSS) is a standard tool for symptom assessment. The
      Psychosis Evaluation tool for Common use by Caregivers (PECC) was constructed in
      Europe some years ago, with the intent to overcome some of the PANSS drawbacks.
      AIMS AND METHODS: To validate PECC on three longitudinal cohorts of schizophrenic
      patients representative of Swedish outpatients (n = 225, six assessments over 5
      years), international forensic patients (n = 186) and matched non-forensic
      controls (n = 116), five assessments over 2 years for both. RESULTS: The factor
      structure of PECC appears to be highly robust. Norm values (in percentiles) were
      calculated on the materials. Such data provides for analyses of symptom profiles
      and improvement over time measured in absolute numbers. Forensic patients appear
      to have a much lower symptom load (except for cognitive symptoms) than the other
      groups. Forensic controls had much shorter inpatient times than any other group
      and never caught up with respect to symptom control, even after 2 years. These
      differences suggest that the scale is clinically valid. CONCLUSION: PECC has a
      more robust factor structure than PANSS and is simpler to use. Percentile norms
      have been constructed for outpatients with schizophrenia in general and forensic
      psychiatry. Percentile scores are accessed readily by the net. PECC is available
      in many languages. Its separate self-harm item may improve assessments of suicide
      risk among patients with schizophrenia.

PMID- 21958349
TI  - Assessing asthma control in UK primary care: use of routinely collected
      prospective observational consultation data to determine appropriateness of a
      variety of control assessment models.
AB  - BACKGROUND: Assessing asthma control using standardised questionnaires is
      recommended as good clinical practice but there is little evidence validating
      their use within primary care. There is however, strong empirical evidence to
      indicate that age, weight, gender, smoking, symptom pattern, medication use,
      health service resource use, geographical location, deprivation, and
      organisational issues, are factors strongly associated with asthma control. A
      good control measure is therefore one whose variation is most explained by these
      factors. METHOD: Eight binary (Yes = poor control, No = good control) models of
      asthma control were constructed from a large UK primary care dataset: the Royal
      College of Physicians 3-Questions (RCP-3Qs); the Jones Morbidity Index; three
      composite measures; three single component models. Accounting for practice
      clustering of patients, we investigated the effects of each model for assessing
      control. The binary models were assessed for goodness-of-fit statistics using
      Pseudo R-squared and Akaikes Information Criteria (AIC), and for performance
      using Area Under the Receiver Operator Characteristic (AUROC). In addition, an
      expanded RCP-3Q control scale (0-9) was derived and assessed with linear
      modelling. The analysis identified which model was best explained by the
      independent variables and thus could be considered a good model of control
      assessment. RESULTS: 1,205 practices provided information on 64,929 patients aged
      13+ years. The RCP-3Q model provided the best fit statistically, with a Pseudo R
      squared of 18%, and an AUROC of 0.79. By contrast, the composite model based on
      the GINA definition of controlled asthma had a higher AIC, an AUROC of 0.72, and
      only 10% variability explained. In addition, although the Peak Expiratory Flow
      Rate (PEFR) model had the lowest AIC, it had an AUROC of 71% and only 6% of
      variability explained. However, compared with the RCP-3Qs binary model, the
      linear RCP-3Q Total Score Model (Scale 0-9), was found to be a more robust 'tool'
      for assessing asthma control with a lower AIC (28,6163) and an R-squared of 33%.
      CONCLUSION: In the absence of a gold standard for assessing asthma control in
      primary care, the results indicate that the RCP-3Qs is an effective control
      assessment tool but, for maximum effect, the expanded scoring model should be
      used.

PMID- 21958351
TI  - Persistent asthma, comorbid conditions and the risk of work disability: a
      prospective cohort study.
AB  - BACKGROUND: This study examined whether asthma alone or together with chronic
      comorbidity is associated with an increased risk of long-term work disability.
      METHODS: We examined data from 2332 asthmatic and 66 354 nonasthmatic public
      sector employees in Finland who responded to a survey between 1997 and 2004.
      Respondents were coded as persistent asthmatics based on the special
      reimbursement for continuous asthma medication by the Social Insurance
      Institution. Data on long-term work disability (sickness absences or disability
      pensions > 90 days) were obtained from national registers. The risk of work
      disability was examined by Cox proportional hazard models adjusted for age,
      gender, socioeconomic status, type of employment contract, and type of employer.
      RESULTS: Asthma increased the risk of all-cause long-term work disability with
      hazard ratio (HR) 1.8 (95% CI 1.62-2.09) compared with controls (no asthma).
      Asthma and one other chronic comorbidity increased the risk of long-term all
      cause work disability with HR 2.2 (95% CI 1.78-2.83). Asthma together with two or
      more other chronic conditions increased the risk with HR 4.5 (95% CI 2.98-6.78).
      Asthma and depression increased the risk with HR 3.6, and the risk was especially
      high for permanent work disability (HR 6.8). Among those with asthma, there were
      more women, obese individuals (BMI >= 30), ex-smokers, and lower-grade nonmanual
      workers. CONCLUSIONS: Asthma is associated with an increased risk of long-term
      all-cause work disability. The risk increases further with chronic comorbidities
      and is especially high in patients with asthma and depression.

PMID- 21958350
TI  - Mismatch repair causes the dynamic release of an essential DNA polymerase from
      the replication fork.
AB  - Mismatch repair (MMR) corrects DNA polymerase errors occurring during genome
      replication. MMR is critical for genome maintenance, and its loss increases
      mutation rates several hundred fold. Recent work has shown that the interaction
      between the mismatch recognition protein MutS and the replication processivity
      clamp is important for MMR in Bacillus subtilis. To further understand how MMR is
      coupled to DNA replication, we examined the subcellular localization of MMR and
      DNA replication proteins fused to green fluorescent protein (GFP) in live cells,
      following an increase in DNA replication errors. We demonstrate that foci of the
      essential DNA polymerase DnaE-GFP decrease following mismatch incorporation and
      that loss of DnaE-GFP foci requires MutS. Furthermore, we show that MutS and MutL
      bind DnaE in vitro, suggesting that DnaE is coupled to repair. We also found that
      DnaE-GFP foci decrease in vivo following a DNA damage-independent arrest of DNA
      synthesis showing that loss of DnaE-GFP foci is caused by perturbations to DNA
      replication. We propose that MutS directly contacts the DNA replication
      machinery, causing a dynamic change in the organization of DnaE at the
      replication fork during MMR. Our results establish a striking and intimate
      connection between MMR and the replicating DNA polymerase complex in vivo.

PMID- 21958352
TI  - Staudinger-phosphonite reactions for the chemoselective transformation of azido
      containing peptides and proteins.
AB  - Site-specific functionalization of proteins by bioorthogonal modification offers
      a convenient pathway to create, modify, and study biologically active
      biopolymers. In this paper the Staudinger reaction of aryl-phosphonites for the
      chemoselective functionalization of azido-peptides and proteins was probed.
      Different water-soluble phosphonites with oligoethylene substituents were
      synthesized and reacted with unprotected azido-containing peptides in aqueous
      systems at room temperature in high conversions. Finally, the Staudinger
      phosphonite reaction was successfully applied to the site-specific modification
      of the protein calmodulin.

PMID- 21958353
TI  - Stages of change: A qualitative study on the implementation of a perinatal audit
      programme in South Africa.
AB  - BACKGROUND: Audit and feedback is an established strategy for improving maternal,
      neonatal and child health. The Perinatal Problem Identification Programme (PPIP),
      implemented in South African public hospitals in the late 1990s, measures
      perinatal mortality rates and identifies avoidable factors associated with each
      death. The aim of this study was to elucidate the processes involved in the
      implementation and sustainability of this programme. METHODS: Clinicians'
      experiences of the implementation and maintenance of PPIP were explored
      qualitatively in two workshop sessions. An analytical framework comprising six
      stages of change, divided into three phases, was used: pre-implementation (create
      awareness, commit to implementation); implementation (prepare to implement,
      implement) and institutionalisation (integrate into routine practice, sustain new
      practices). RESULTS: Four essential factors emerged as important for the
      successful implementation and sustainability of an audit system throughout the
      different stages of change: 1) drivers (agents of change) and team work, 2)
      clinical outreach visits and supervisory activities, 3) institutional perinatal
      review and feedback meetings, and 4) communication and networking between health
      system levels, health care facilities and different role-players.During the pre
      implementation phase high perinatal mortality rates highlighted the problem and
      indicated the need to implement an audit programme (stage 1). Commitment to
      implementing the programme was achieved by obtaining buy-in from management,
      administration and health care practitioners (stage 2).Preparations in the
      implementation phase included the procurement and installation of software and
      training in its use (stage 3). Implementation began with the collection of data,
      followed by feedback at perinatal review meetings (stage 4).The
      institutionalisation phase was reached when the results of the audit were
      integrated into routine practice (stage 5) and when data collection had been
      sustained for a longer period (stage 6). CONCLUSION: Insights into the factors
      necessary for the successful implementation and maintenance of an audit programme
      and the process of change involved may also be transferable to similar low- and
      middle-income public health settings where the reduction of the neonatal
      mortality rate is a key objective in reaching Millennium Development Goal 4. A
      tool for reflecting on the implementation and maintenance of an audit programme
      is also proposed.

PMID- 21958354
TI  - Synthesis, spectroscopy and antimicrobial activity of iron complexes of some
      smoke flavour compounds.
AB  - Iron (III) complexes of some smoke flavour compounds (2-allyloxyphenol, guaiacol,
      eugenol and 2-ethoxyphenol) were synthesised and characterised by UV-Vis
      spectroscopy and ESI mass spectrometry. The ligand metal binding ratio was found
      to be 1:1 by the Job plot method. Antimicrobial activity of the ligand iron
      complex was determined against Bacillus subtilis, Escherichia coli,
      Staphylococcus aureus and Pseudomonas aeruginosa. This activity was compared with
      that of the free ligand (four smoke flavour compounds). While enhanced
      antimicrobial activities of guaiacol and 2-ethoxyphenol iron complexes were
      observed, this effect was, however, limited for eugenol and 2-allyloxyphenol iron
      complexes. In this study, it was established for the first time that not only do
      smoke flavour compounds complex with iron which could potentially retard food
      spoilage, but also after complexation, some complexes attain antimicrobial
      activities compared to the inactive free ligands.

PMID- 21958355
TI  - Brachial plexus block in phantom limb pain: a case report.
AB  - OBJECTIVE: The purpose of this case report is twofold: first, to present evidence
      of long-lasting relief in a patient suffering from phantom limb pain after
      pharmacologically blocking his plexus brachialis and, second, to replicate
      results from a previous study focusing on cortical reorganization and phantom
      limb pain. SUBJECT: Before regional anesthesia, the patient suffered from a
      phantom hand that cramped and was immovable. SETTING: We performed a diagnostic
      axillary blockade of the brachial plexus to differentiate peripheral from more
      central contributions to phantom limb pain. RESULTS: During blockade of the
      brachial plexus, the patient reported a reduction of phantom limb pain for the
      first time following years of suffering and a complete loss of cramping together
      with muscle relaxation of the phantom hand. Additionally, we found cortical
      reorganization in the primary somatosensory cortex (re-reorganization).
      Strikingly, the relaxed phantom limb together with the reduction of phantom limb
      pain remained preserved even 6 months after blockade of the brachial plexus.
      CONCLUSIONS: A single temporary blockade of the brachial plexus may relieve
      phantom limb pain and unpleasant phantom feelings (cramping) for an extended
      period.

PMID- 21958356
TI  - Cytokine expression in the seminal plasma and its effects on fertilisation rates
      in an IVF cycle.
AB  - Cytokines are released by various immunocompetent cell subsets in the male
      urogenital tract and are thought to affect sperm cell function and reproductive
      process. The aim of the study was to evaluate the levels and a possible role of
      seven seminal plasma cytokines with fertilisation rates in men attending an in
      vitro fertilisation (IVF) programme. A total of 36 men of couples who were
      undergoing traditional IVF in a regional reproductive medicine unit were
      recruited into this prospective study. Cytokines such as interleukin (IL)-6, IL
      8, IL-10, IL-11, IL-12, tumour necrosis factor alpha (TNF-alpha) and interferon
      gamma (IFN-gamma) in the seminal plasma were determined using enzyme linked
      immunosorbent assay. IL-6, IL-8, IL-10, IL-11 and IFN-gamma were detected in all
      samples. IL-12, and TNF-alpha were detected in most samples. Levels of IL-11 were
      significantly higher in the good fertiliser group (P <= 0.05). Positive
      correlation between cytokines such as IL-6 and IL-8 (P < 0.03), IL-10 and IL-11
      (P < 0.001) and IFN-gamma and IL-10 and IL-11 (P < 0.04 and P < 0.0001
      respectively) were found. Our study confirms that the six cytokines other than IL
      11 do not affect spermatozoon-oocyte interaction and fertilisation rates in IVF.
      IL-11 could have a role in the fertilising capacity of the spermatozoa.
      Significant correlation exists among these cytokines which shows that cytokines
      rarely act in isolation but rather in a network.

PMID- 21958357
TI  - Measuring technology self efficacy: reliability and construct validity of a
      modified computer self efficacy scale in a clinical rehabilitation setting.
AB  - PURPOSE: To describe a modification of the computer self efficacy scale for use
      in clinical settings and to report on the modified scale's reliability and
      construct validity. METHODS: The computer self efficacy scale was modified to
      make it applicable for clinical settings (for use with older people or people
      with disabilities using everyday technologies). The modified scale was piloted,
      then tested with patients in an Australian inpatient rehabilitation setting (n =
      88) to determine the internal consistency using Cronbach's alpha coefficient.
      Construct validity was assessed by correlation of the scale with age and
      technology use. Factor analysis using principal components analysis was
      undertaken to identify important constructs within the scale. RESULTS: The
      modified computer self efficacy scale demonstrated high internal consistency with
      a standardised alpha coefficient of 0.94. Two constructs within the scale were
      apparent; using the technology alone, and using the technology with the support
      of others. Scores on the scale were correlated with age and frequency of use of
      some technologies thereby supporting construct validity. CONCLUSIONS: The
      modified computer self efficacy scale has demonstrated reliability and construct
      validity for measuring the self efficacy of older people or people with
      disabilities when using everyday technologies. This tool has the potential to
      assist clinicians in identifying older patients who may be more open to using new
      technologies to maintain independence.

PMID- 21958358
TI  - Eruptive vellus hair cysts: a systematic review.
AB  - We report the results of the first systematic review of the worldwide literature
      on eruptive vellus hair cysts (EVHC). It is likely that EVHC are less rare than
      it may appear from the scarcity of related publications in the literature. EVHC
      may be present at birth and may appear at any age, although they show a clear
      trend towards occurring during the first 3 decades of life. A strong clue to the
      heavy influence of genes on the occurrence of EVHC is provided by the numerous
      reports of families in whom two or more members were affected. EVHC lesions
      present clinically in a rather monomorphous fashion, i.e. round, dome-shaped,
      skin-colored, asymptomatic, soft-tender papules with a smooth surface and grouped
      or disseminated in a symmetric pattern. EVHC may affect any cutaneous area, even
      if the upper part of the body and some distribution patterns are particularly
      frequent and recognizable, i.e. cephalic, upper trunk around the midline, upper
      limb including axillae, and proximal lower limb. Such a distribution is likely
      not random and seems to grossly overlap with that of pilosebaceous and apocrine
      units. Like clinical morphology, the histologic features of EVHC papules are
      rather monomorphous, indeed, the diagnostic hallmark being the presence of vellus
      hair shafts within the cystic space. Peculiar subgroups (familial, late-onset,
      unilesional, and associated with steatocystoma multiplex) are also identified and
      discussed. In conclusion, EVHC are basically a cosmetic concern to patients but
      represent a chronic and difficult-to-treat condition. On the basis of our review,
      future studies are warranted, mainly concerning (i) further nosographic framing
      involving genetic and tissue analysis, (ii) implementation of non-invasive
      diagnostic procedures, and (iii) therapeutic trials of interventions shown to
      achieve some effectiveness.

PMID- 21958359
TI  - Alpha-pyrones and diketopiperazine derivatives from the marine-derived
      actinomycete Nocardiopsis dassonvillei HR10-5.
AB  - Three new alpha-pyrones, nocapyrones E-G (1-3), and three new diketopiperazine
      derivatives, nocazines A-C (4-6), together with a new oxazoline compound,
      nocazoline A (7), were isolated from the marine-derived actinomycete 
      Nocardiopsis dassonvillei  HR10-5. The new structures of 1-7 were determined by
      spectroscopic analysis, X-ray single-crystal diffraction, CD spectra, and
      modified Mosher and Marfey methods. Compounds 1-3 showed modest antimicrobial
      activity against  Bacillus subtilis  with MIC values of 26, 14, and 12 MUM,
      respectively.

PMID- 21958360
TI  - Intracellular monitoring of target protein production in Staphylococcus aureus by
      peptide tag-induced reporter fluorescence.
AB  - An intracellular approach for monitoring protein production in Staphylococcus
      aureus is described. mCherry, fused to the dodecapeptide Tip, was capable of
      inducing tetracycline repressor (TetR). Time- and concentration-dependent
      production of mCherry could be correlated to TetR-controlled GFPmut2 activity.
      This approach can potentially be extended to native S. aureus proteins.

PMID- 21958361
TI  - Effect of drying of figs (Ficus carica L.) on the contents of sugars, organic
      acids, and phenolic compounds.
AB  - Fresh figs were subjected to two different drying processes: sun-drying and oven
      drying. To assess their effect on the nutritional and health-related properties
      of figs, sugars, organic acids, single phenolics, total phenolics, and
      antioxidant activity were determined before and after processing. Samples were
      analyzed three times in a year, and phenolic compounds were determined using high
      performance liquid chromatography coupled with mass spectrometry (HPLC-MS). In
      figs, monomer sugars predominate, which is important nutritional information, and
      the content of sugars as well as organic acids in fresh figs was lower than in
      dried fruits. However, the best sugar/organic acid ratio was measured after the
      sun-drying process. Analysis of individual phenolic compounds revealed a higher
      content of all phenolic groups determined after the oven-drying process, with the
      exception of cyanidin-3-O-rutinoside. Similarly, higher total phenolic content
      and antioxidant activity were detected after the drying process. With these
      results it can be concluded that the differences in analyzed compounds in fresh
      and dried figs are significant. The differences between the sun-dried and oven
      dried fruits were determined in organic acids, sugars, chlorogenic acid,
      catechin, epicatechin, kaempferol-3-O-glucoside, luteolin-8-C-glucoside, and
      total phenolic contents. The results indicate that properly dried figs can be
      used as a good source of phenolic compounds.

PMID- 21958362
TI  - Areca nut extracts suppress the differentiation and functionality of human
      monocyte-derived dendritic cells.
AB  - BACKGROUND AND OBJECTIVE: Areca quid chewing, a major risk factor contributing to
      the occurrence of oral cancer and precancer, has been reported to be associated
      with the severity and high prevalence of periodontal diseases in areca quid
      chewers. As dendritic cells are critically involved in the regulation of innate
      and adaptive immunity in oral mucosa, the objective of the present study was to
      investigate the effect of areca nut extracts (ANE) on the differentiation and
      reactivity of dendritic cells derived from monocytes. MATERIAL AND METHODS: Human
      peripheral blood monocytes were cultured in the presence of granulocyte-monocyte
      colony-stimulating factor and interleukin-4 for 7 d to generate dendritic cells.
      To examine the effect of ANE on the generation of dendritic cells, the monocytes
      were exposed to ANE throughout the 7 d culture period. In addition, the effect of
      ANE on the maturation of monocyte-derived dendritic cells induced by
      lipopolysaccharide (LPS) was examined. RESULTS: Monocytes cultured in granulocyte
      monocyte colony-stimulating factor and interleukin-4 exhibited a typical
      phenotype of dendritic cells, as evidenced by the heightened expression of human
      leukocyte antigen (HLA)-DR, CD11c and the co-stimulatory molecules CD40, CD80 and
      CD86. Exposure of the monocytes to ANE did not influence the expression of HLA-DR
      and CD11c, but markedly attenuated the proportion of CD40-positive cells and the
      mean fluorescence intensity of CD86. The expression of co-stimulatory molecules
      in LPS-activated dendritic cells was not affected, whereas the mRNA expression of
      interleukin-12 induced by LPS was markedly suppressed by ANE treatment in a
      concentration-dependent manner. CONCLUSION: These results suggest that ANE
      exposure interfered with the differentiation of dendritic cells from monocytes.
      Moreover, the functionality of mature monocyte-derived dendritic cells was
      attenuated in the presence of ANE.

PMID- 21958363
TI  - Elongation of the Fe-His bond in the alpha subunit induced by binding of the
      allosteric effector bezafibrate to hemoglobins.
AB  - Human adult hemoglobin (HbA), possessing an alpha(2)beta(2) tetramer structure,
      efficiently transports oxygen from the lungs to the tissues. The oxygen affinity
      of HbA has been shown to be regulated by organic phosphates such as 2,3
      bisphosphoglycerate (BPG). Bezafibrate (BZF) is also known to alter the oxygen
      affinity of HbA through a mechanism largely different from that of BPG. The
      interaction of HbA with BZF has been characterized by (1)H NMR to elucidate the
      molecular mechanism responsible for the functional alteration of HbA.
      Paramagnetically shifted heme methyl proton signals of only the alpha subunit of
      met-azido HbA exhibited sizable downfield shifts in the presence of BZF. Since
      met-azido HbA exhibits the so-called thermal spin equilibrium between high and
      low spin states, the BZF-induced shift changes observed for the alpha signals can
      be attributed to an increase in the high spin contents in the subunit, possibly
      due to the elongation of the Fe-His bond.

PMID- 21958364
TI  - Arterial stiffness profiles: investigating various sections of the arterial tree
      of African and Caucasian people.
AB  - In Africans, arterial stiffness progression seems more pronounced compared to
      Caucasians. We compared the arterial stiffness profiles of different age groups
      and focused on muscular arteries and two more central arterial segments in
      African and Caucasian people from South Africa. In African (N = 374) and
      Caucasian (N = 376) participants (20-70 years), we measured carotid-radial (C-R)
      and carotid-dorsalis pedis (C-DP) pulse wave velocity (PWV) and aortic
      characteristic impedance (Zao). Major findings were that normotensive and high
      normal/hypertensive (HT) Caucasians indicated increased trends of C-R PWV with
      aging (P = .029 and P = .067), not seen in the African groups (P = .122 and P =
      .526). Both ethnic groups showed significant increases of C-DP PWV and Zao with
      aging. High-normal/hypertensive Africans had significantly stiffer arteries than
      hypertensive Caucasians for almost all age groups, and for all stiffness
      measures. African C-R PWV correlated significantly with blood pressure (BP), but
      not with age. Opposite results were observed for Caucasians. In conclusion, the
      stiffness of muscular arteries is already elevated in young Africans, in both
      those with normal or elevated BP. This is possibly due to an earlier
      deterioration during childhood, or perhaps already present from birth. Also, in
      Caucasians stiffness seems more age-related, while in Africans it seems to be
      more pressure-related.

PMID- 21958365
TI  - The importance of stressful family events in psoriatic patients: a retrospective
      study.
AB  - BACKGROUND: Psychosomatic stress events are believed to play an important role in
      psoriasis either by inducing or worsening the disease. OBJECTIVE: In this
      article, we compared the role of family stress events against other types of
      stress events on the psychological well being of patients and on their skin
      disease. We used our sample of psoriasis patients with said stress events.
      METHOD: Patients underwent a dermatological examination which was evaluated
      through the PASI index. Simultaneously, they underwent interviews for
      psychological evaluations. The Hamilton scales were administered to assess
      anxiety and depression (Ham-A scores significant >20, Ham-D >15). RESULTS: It has
      been demonstrated that family stress influences the psychological well being more
      than other types of daily stress events. In fact, people with family stress
      events reported higher value HAM-A (P = 0.03) and HAM-D (P = 0.02) compared with
      those who reported other types of stress events. Women reported higher values of
      HAM-A and HAM-D than men. The value of PASI in the two groups (with family stress
      events and those with other stress events) was not statistically significant.
      CONCLUSION: Results obtained from this analysis show the importance of family
      stress events on the quality of life and on psychiatric and dermatological
      status. For the psychological morbidity, a parallel approach of both bio
      psychiatric and skin care is recommended, especially for women.

PMID- 21958366
TI  - Sedative load of medications prescribed for older people with dementia in care
      homes.
AB  - BACKGROUND: The objective of this study was to determine the sedative load and
      use of sedative and psychotropic medications among older people with dementia
      living in (residential) care homes. METHODS: Medication data were collected at
      baseline and at two further time-points for eligible residents of six care homes
      participating in the EVIDEM-End Of Life (EOL) study for whom medication
      administration records were available. Regular medications were classified using
      the Anatomical Therapeutic Chemical classification system and individual sedative
      loads were calculated using a previously published model. RESULTS: At baseline,
      medication administration records were reviewed for 115 residents; medication
      records were reviewed for 112 and 105 residents at time-points 2 and 3
      respectively. Approximately one-third of residents were not taking any
      medications with sedative properties at each time-point, while a significant
      proportion of residents had a low sedative load score of 1 or 2 (54.8%, 59.0% and
      57.1% at baseline and time-points 2 and 3 respectively). More than 10% of
      residents had a high sedative load score (>= 3) at baseline (12.2%), and this
      increased to 14.3% at time-points 2 and 3. Approximately two-thirds of residents
      (66.9%) regularly used one or more psychotropic medication(s). Antidepressants,
      predominantly selective serotonin re-uptake inhibitors (SSRIs), were most
      frequently used, while antipsychotics, hypnotics and anxiolytics were less
      routinely administered. The prevalence of antipsychotic use among residents was
      19.0%, lower than has been previously reported for nursing home residents.
      Throughout the duration of the study, administration of medications recognised as
      having prominent sedative adverse effects and/or containing sedative components
      outweighed the regular use of primary sedatives. CONCLUSIONS: Sedative load
      scores were similar throughout the study period for residents with dementia in
      each of the care homes. Scores were lower than previously reported in studies
      conducted in long-term care wards which have on-site clinical support.
      Nevertheless, strategies to optimise drug therapy for care home residents with
      dementia which rely on clinicians external to the care home for support and
      medication review are required.

PMID- 21958367
TI  - A comparison of depressive symptoms in elderly medical inpatients and the elderly
      in a population-based health study (the Nord-Trondelag Health Study 3).
AB  - AIM: To compare depression in a sample of the medically hospitalized elderly with
      elderly people participating in a population-based health study in Norway and
      further to study the odds for depression, controlling for demographic and health
      differences between the two samples. METHOD: This cross-sectional observational
      study evaluated 484 medical inpatients from rural areas and 10,765 drawn from the
      Nord-Trondelag Health Study 3 (HUNT-3 Study) including participants from rural
      and urban areas. All participants were elderly (>=65 years) with a mean (+/-
      standard deviation) age of 80.7 +/- 7.4 and 73.3 +/- 6.3 years, respectively.
      Symptoms of depression were screened by the Hospital Anxiety and Depression Scale
      (HAD). RESULTS: The prevalence of symptoms indicating mild, moderate or more
      severe depression (depression score >=8) was about the same in both groups. In
      regression analyses, adjusting demographic and health differences, the odds for
      depression was lower for the elderly in the hospital sample than in the HUNT-3
      Study. Older age, male gender, perceiving general health as poor, having impaired
      ability to function in daily life, previous consultation or treatment for
      emotional problems and anxiety (anxiety score >=8) were associated with increased
      odds for depression in the elderly independent of being hospitalized or not.
      CONCLUSION: Surprisingly, we found the odds for depression after controlling for
      demographic and health variables to be lower in the hospitalized elderly
      individuals than in the elderly participating in the population-based health
      study. The health variables that were most strongly associated with an increased
      risk of depression were poor physical health and anxiety.

PMID- 21958368
TI  - Galectin-11 induction in the gastrointestinal tract of cattle following nematode
      and protozoan infections.
AB  - Galectin-11 (LGALS11) has been suggested to play an important role in protective
      immunity against gastrointestinal nematodes in ruminants. However, in cattle,
      this molecule has not been characterized in detail. In the current study, it was
      shown that transcription of LGALS11 was highly inducible in the bovine abomasal
      mucosa after an Ostertagia ostertagi infection. LGALS11 protein expression was
      also increased in the abomasal mucosa following O. ostertagi infection and
      localized to the nucleus and cytoplasm of epithelial cells and the mucus. Using
      in vitro abomasal epithelial cell cultures, it was shown that LGALS11 induction
      was associated with the proliferative and dedifferentiated status of cells.
      However, LGALS11 was not induced following stimulation with O. ostertagi
      excretory-secretory products. These results suggest that LGALS11 induction in
      vivo may be an indirect rather than a direct effect of the parasite on the
      epithelium. In addition, LGALS11 transcript was also detected in the abomasal
      lymph nodes where it was shown to be transcribed in MHCII+ cells; however,
      transcription levels in the lymph nodes were not altered after O. ostertagi
      infection. In addition, LGALS11 was also induced in the small intestine by
      different types of parasites, including the nematode Cooperia oncophora and the
      protozoan parasite Giardia duodenalis.

PMID- 21958370
TI  - NK cell function and antibodies mediating ADCC in HIV-1-infected viremic and
      controller patients.
AB  - Natural killer (NK) cells have been suggested to play a protective role in HIV
      disease progression. One potent effector mechanism of NK cells is antibody
      dependent cellular cytotoxicity (ADCC) mediated by antiviral antibodies binding
      to the FcgammaRIIIa receptor (CD16) on NK cells. We investigated NK cell-mediated
      ADCC function and the presence of ADCC antibodies in plasma from 20 HIV-1
      infected patients and 10 healthy donors. The HIV-positive patients were divided
      into two groups: six who controlled viremia for at least 8 y without treatment
      (controllers), and 14 who were persistently viremic and not currently on
      treatment. Plasma from both patient groups induced NK cell IFN-gamma expression
      and degranulation in response to HIV-1 envelope (Env) gp140-protein-coated cells.
      Patient antibodies mediating ADCC were largely directed towards the Env V3 loop,
      as identified by a gp140 protein lacking the V3 loop. Interestingly, in two
      controllers ADCC-mediating antibodies were more broadly directed to other parts
      of Env. A high viral load in patients correlated with decreased ADCC-mediated
      cytolysis of gp140-protein-coated target cells. NK cells from both infected
      patients and healthy donors degranulated efficiently in the presence of antibody
      coated HIV-1-infected Jurkat cells. In conclusion, the character of ADCC
      mediating antibodies differed in some controllers compared to viremic patients.
      NK cell ADCC activity is not compromised in HIV-infected patients.

PMID- 21958369
TI  - Correlations between vaccinia-specific immune responses within a cohort of armed
      forces members.
AB  - Widespread vaccination with vaccinia virus (VACV) resulted in the eradication of
      smallpox; however, the licensed VACV-containing vaccines are associated with
      adverse events (AEs), making them unsuitable for certain high-risk populations. A
      better understanding of the host immune response following smallpox vaccination
      could result in vaccines with similar immunogenicity profiles to pre-eradication
      vaccines with a lower incidence of AEs. To study the immune response to VACV, we
      recruited 1,076 armed forces members who had been vaccinated with one dose of
      Dryvax((r)). We measured multiple VACV-specific immune responses: neutralizing
      antibody titer, the level of 12 secreted cytokines in peripheral blood
      mononuclear cell (PBMC) cultures (IL-1beta, IL-2, IL-4, IL-6, IL-10, IL-12p40, IL
      12p70, TNF-alpha, IFN-gamma, IFN-alpha, IFN-beta, and IL-18), and the number of
      IFN-gamma- and CD8(+) IFN-gamma-secreting cells. We analyzed these data to
      determine correlations between immune response measures. We detected a strong
      proinflammatory response in concert with a Th-1-like cytokine response pattern at
      a median time point of 15.3 mo following primary vaccination. We also detected
      correlations between neutralizing antibody titer and secreted IL-2, as well as
      secreted IFN-gamma (p=0.009 and p=0.0007, respectively). We also detected strong
      correlations between the proinflammatory cytokines IL-1beta, TNF-alpha, IL-6, and
      IL-12p40 (p<0.0001). These results further advance our knowledge of vaccinia
      specific cellular immune responses. Notably, vaccine-induced proinflammatory
      responses were not correlated with neutralizing antibody titers, suggesting that
      further attenuation to reduce inflammatory immune responses may result in
      decreased AEs without sacrificing VACV immunogenicity and population
      seropositivity.

PMID- 21958371
TI  - Human-leukocyte antigen class I Cw 1502 and class II DR 0301 genotypes are
      associated with resistance to severe acute respiratory syndrome (SARS) infection.
AB  - One-hundred and thirty confirmed cases of severe acute respiratory syndrome
      (SARS) were recruited to evaluate their anti-SARS-coronavirus (CoV) antibody
      status and human leukocyte antigen (HLA) types in September 2006, 3 y after the
      SARS outbreaks in Taiwan. Western blot assay showed that 6.9% of participants
      still had anti-spike and anti-nucleocapside antibodies. A case-control study of
      the association of HLA with SARS revealed that the HLA-Cw1502 and DR0301 alleles
      conferred resistance against SARS infection (p<0.05).

PMID- 21958372
TI  - Cytometric microsphere array for subtyping avian influenza virus.
AB  - Avian influenza is a highly contagious disease, and different subtypes of avian
      influenza virus (AIV) have different levels of pathogenicity. A microsphere-based
      fluorescent assay was initially established for subtyping AIV. DNA fragments were
      amplified with biotinylated primers. AIV subtype-specific DNA probes with an
      amino-linker at the 5' end were covalently bound with carboxy-modified encoded
      beads. The modified beads and the denatured DNA fragments were mixed together for
      hybridization. Then, quantum dots-streptavidin (QDs-streptavidin) was added to
      conjugated biotinylated PCR products. The reaction products were screened by flow
      cytometry. AIV strains (such as H5N1 and H9N2) could be determined and subtyped
      according to their combination of encoded beads and fluorescent QDs. The method's
      combined sensitivity of the nucleic acids of H5N1 and H9N2 avian influenza virus
      at a threshold of 74 pg and 1 pg could be detected. This is a powerful method for
      detecting many pathogens or many types of a pathogen simultaneously.

PMID- 21958374
TI  - External-stimuli responsive photophysics and liquid crystal properties of self
      assembled "phosphole-lipids".
AB  - A series of new amphiphilic phosphonium materials that combine the electronic
      features of phospholes with self-assembly features of lipids were synthesized.
      Variable concentration/temperature and 2D NMR studies suggested that the systems
      undergo intramolecular conformation changes between a "closed" and "open" form
      that are triggered by intermolecular interactions. The amphiphilic features of
      the phospholium species also induce liquid crystalline and soft crystal phase
      behavior in the solid state, which was studied by differential scanning
      calorimetry (DSC), polarized optical microscopy (POM), and variable temperature
      powder X-ray diffraction (VT-PXRD). The studies revealed that both conjugated
      backbones and counteranions work together to organize the systems into different
      morphologies (liquid crystal/soft crystal). Dithieno[3,2-b:2',3'-d]phosphole
      based compounds exhibit enhanced emission in the solid state and at low
      temperature in solution due to aggregation-induced enhanced emission (AIEE).
      Photoinduced electron transfer (PET) induced via the alkoxybenzyl group at the
      phosphonium center in the fused-ring systems can be effectively suppressed
      through intermolecular charge transfer (ICT) processes within the main scaffold
      of a nonfused system, which was confirmed by static and dynamic fluorescence
      spectroscopy. The dynamic features of these new materials also endow the systems
      with external-stimuli responsive photophysical properties that can be triggered
      by temperature and/or mechanical forces.

PMID- 21958373
TI  - Preferential replication of vaccinia virus in the ovaries is independent of
      immune regulation through IL-10 and TGF-beta.
AB  - Vaccinia virus (VACV) exhibits a strong tropism for ovarian tissue and can cause
      ovary pathology and sterility. Why VACV preferentially accumulates in this organ
      is not known. Here we show that multiple immune cell populations infiltrated the
      ovaries following VACV infection, including virus-specific CD8 T cells making
      both IFN-gamma and TNF. This was also accompanied by the induction of interleukin
      (IL)-10 and TGF-beta, suggesting that VACV may exploit the ovarian environment
      for immune evasion via induction of these suppressive cytokines. To test this we
      used several strategies, including neutralizing these cytokines, and exogenous
      targeting of the T-cell response, to determine if this inhibited virus
      replication in the ovaries. We found that the VACV-specific CD8 T-cell immunity
      and the clearance of virus were not enhanced in the ovaries of infected mice in
      which IL-10 receptor (IL-10R) was blocked with antagonist antibody. VACV
      replication was also only moderately affected in the ovaries of infected IL-10
      knockout mice. Similarly, blockade of TGF-beta with antagonist antibody
      demonstrated no effect on CD8 T-cell immunity or VACV replication. Lastly, an
      agonist antibody targeting the tumor necrosis factor receptor superfamily member
      OX40 (TNFRSF4) enhanced the number of VACV-specific CD8 T cells producing IFN
      gamma in lymphoid tissue, but had no effect on CD8 T-cell infiltration of the
      ovaries or on the viral load. Collectively, the results indicate that
      preferential replication of VACV in the ovaries may not be dependent on immune
      suppressive mechanisms in this tissue.

PMID- 21958375
TI  - Toward the development of the direct and selective detection of nitrates by a
      bioinspired Mo-Cu system.
AB  - The development of a new platform for the direct and selective detection of
      nitrates is described. Two thioether-based chemosensors and the corresponding
      sulfoxides and sulfones were prepared, and their photophysical properties were
      evaluated. Upon selective sulfoxidation of these thioethers with nitrates via an
      oxygen-transfer reaction promoted by a bioinspired Mo-Cu system, significant
      fluorescence shifts were measured. A selective response of these systems,
      discriminating between nitrate salts and H(2)O(2), was also shown.

PMID- 21958376
TI  - rpb2 is a reliable reference gene for quantitative gene expression analysis in
      the dermatophyte Trichophyton rubrum.
AB  - The selection of reference genes used for data normalization to quantify gene
      expression by real-time PCR amplifications (qRT-PCR) is crucial for the accuracy
      of this technique. In spite of this, little information regarding such genes for
      qRT-PCR is available for gene expression analyses in pathogenic fungi. Thus, we
      investigated the suitability of eight candidate reference genes in isolates of
      the human dermatophyte Trichophyton rubrum subjected to several environmental
      challenges, such as drug exposure, interaction with human nail and skin, and heat
      stress. The stability of these genes was determined by geNorm, NormFinder and
      Best-Keeper programs. The gene with the most stable expression in the majority of
      the conditions tested was rpb2 (DNA-dependent RNA polymerase II), which was
      validated in three T. rubrum strains. Moreover, the combination of rpb2 and chs1
      (chitin synthase) genes provided for the most reliable qRT-PCR data normalization
      in T. rubrum under a broad range of biological conditions. To the best of our
      knowledge this is the first report on the selection of reference genes for qRT
      PCR data normalization in dermatophytes and the results of these studies should
      permit further analysis of gene expression under several experimental conditions,
      with improved accuracy and reliability.

PMID- 21958377
TI  - The effect of supervised Tai Chi intervention compared to a physiotherapy program
      on fall-related clinical outcomes: a randomized clinical trial.
AB  - PURPOSE: To assess some fall-related clinical variables (balance, gait, fear of
      falling, functional autonomy, self-actualization and self-efficacy) that might
      explain the fact that supervised Tai Chi has a better impact on preventing falls
      compared to a conventional physiotherapy program. METHODS: The participants (152
      older adults over 65 who were admitted to a geriatric day hospital program) were
      randomly assigned to either a supervised Tai Chi group or the usual
      physiotherapy. The presence of the clinical variables related to falls was
      evaluated before the intervention (T1), immediately after (T2), and 12 months
      after the end of the intervention (T3). RESULTS: Both exercise programs
      significantly improved fall-related outcomes but only the Tai Chi intervention
      group decreased the incidence of falls. For both groups, most variables followed
      the same pattern, i.e. showed significant improvement with the intervention
      between T1 and T2, and followed by a statistically significant decrease at the T3
      evaluation. However, self-efficacy was the only variable that improved solely
      with the Tai Chi intervention (p = 0.001). CONCLUSIONS: The impact of supervised
      Tai Chi on fall prevention can not be explained by a differential effect on
      balance, gait and fear of falling. It appeared to be related to an increase of
      general self-efficacy, a phenomenon which is not seen in the conventional
      physiotherapy program.

PMID- 21958378
TI  - Pharmacogenetics of oxaliplatin as adjuvant treatment in colon carcinoma: are
      single nucleotide polymorphisms in GSTP1, ERCC1, and ERCC2 good predictive
      markers?
AB  - PURPOSE: Adjuvant chemotherapy improves survival in stage III colon cancer
      patients. However, a subgroup of patients still develops recurrent disease at
      some point in time, partly because of the ineffectiveness of the chemotherapy.
      Predictive markers of response are therefore crucial. Our aim was to study the
      predictive value of functional polymorphisms in genes involved in the metabolism
      of oxaliplatin and in DNA repair in stage III colon cancer patients. MATERIALS
      AND METHODS: Normal DNA was isolated from 98 patients diagnosed with stage III
      colon carcinoma. Single nucleotide polymorphisms (SNPs) in three genes (the
      excision repair cross-complementing genes ERCC1 [19007T>C] and ERCC2 [2251A>C],
      and the glutathione S-transferase pi 1 gene [GSTP1 313A>G]) were tested by PCR
      followed by digestion with restriction enzymes or by direct sequencing. These
      genes and SNPs were selected on the basis of their reported associations with
      oxaliplatin response in colorectal cancer. RESULTS: The genotype frequencies were
      in Hardy-Weinberg equilibrium. GSTP1 and ERCC2 polymorphisms were significantly
      associated with sex. The AA genotype of GSTP1 313A>G was more frequent in men
      than in women (59% vs 30%, p = 0.02), and the CC genotype of ERCC2 2251A>C was
      significantly more frequent in women than in men (24% vs 6%, p = 0.02). In
      univariate and multivariate survival analysis, none of the tested polymorphisms
      seemed to influence disease-free survival. The GSTP1 AA genotype had different
      effects on survival between men and women; homozygous A men had significantly
      worse cancer-specific survival and overall survival than women with the same
      genotype (log rank p = 0.029 and p = 0.015, respectively). CONCLUSION: None of
      the tested polymorphisms is likely to be a reliable marker of response to
      oxaliplatin therapy. The GSTP1 313A>G homozygous A genotype may have a prognostic
      value in male patients.

PMID- 21958380
TI  - Ten-year follow-up of early intensive self-management guidance in newly diagnosed
      patients with asthma.
AB  - OBJECTIVE: We assessed the 10-year effectiveness of self-management guidance in a
      prospective follow-up study of patients with asthma when inhaled corticosteroids
      were used from the beginning in the treatment. METHODS: Consecutive newly
      diagnosed asthmatics (n = 162) were randomized: 80 to an intervention group (IG)
      and 82 to a control group (CG). Lung function (LF), airway hyperresponsiveness
      (AHR), and health-related quality of life (HRQoL) were examined at 10 years.
      RESULTS: The advantages of intensive education with regards to LF measured by
      forced expiratory volume in 1 second and forced vital capacity were seen only
      after the first year. Later, there were no statistically significant differences
      in any parameters between the groups. However, during 10-year follow-up, peak
      expiratory flow, AHR, and HRQoL improved significantly in both groups (no
      differences as regards gender, smoking, or atopy). At 10 years, 68% of the IG and
      75% of the CG patients still showed AHR after histamine challenge. Generic HRQoL
      scores in both groups equaled that of the age-standardized group a general
      population but only 50% in the IG and 55% in the CG had normal disease-specific
      HRQoL scores. According to Global Initiative for Asthma (GINA) criteria 23% of
      patients in the IG and 25% in the CG had asthma under control. CONCLUSIONS: The
      effectiveness of intensive self-management education could be shown only in the
      short term. The groups did not differ significantly in any of the parameters
      investigated, and showed nearly normal LF and HRQoL. AHR improved only partly and
      only a minority of the patients had asthma under good control according to GINA
      criteria. This study showed that evaluation of asthma using LF alone does not
      show the whole truth about asthma treatment results. HRQoL should be used in
      conjunction with GINA criteria, to assess asthma treatment outcomes. The value
      and importance of AHR for the evaluation of treatment remains obscure.

PMID- 21958381
TI  - Mizoroki-Heck reaction of (1-fluorovinyl)methyldiphenylsilane with aryl iodides.
AB  - The Mizoroki-Heck reaction of (1-fluorovinyl)methyldiphenylsilane with a variety
      of aryl iodides was accomplished under the conditions composing Pd(OAc)(2),
      Ag(2)CO(3) and MS 4 A in 1,4-dioxane to give the corresponding (E)-beta-aryl
      (alpha-fluorovinyl)methyldiphenylsilanes with excellent stereoselectivity.

PMID- 21958382
TI  - Structural chemistry, monoclinic-to-orthorhombic phase transition, and CO2
      adsorption behavior of the small pore scandium terephthalate, Sc2(O2CC6H4)CO2)3,
      and its nitro- and amino-functionalized derivatives.
AB  - The crystal structure of the small pore scandium terephthalate
      Sc(2)(O(2)CC(6)H(4)CO(2))(3) (hereafter Sc(2)BDC(3), BDC = 1,4
      benzenedicarboxylate) has been investigated as a function of temperature and of
      functionalization, and its performance as an adsorbent for CO(2) has been
      examined. The structure of Sc(2)BDC(3) has been followed in vacuo over the
      temperature range 140 to 523 K by high resolution synchrotron X-ray powder
      diffraction, revealing a phase change at 225 K from monoclinic C2/c (low
      temperature) to Fddd (high temperature). The orthorhombic form shows negative
      thermal expansivity of 2.4 * 10(-5) K(-1): Rietveld analysis shows that this
      results largely from a decrease in the c axis, which is caused by carboxylate
      group rotation. (2)H wide-line and MAS NMR of deuterated Sc(2)BDC(3) indicates
      reorientation of phenyl groups via pi flips at temperatures above 298 K. The same
      framework solid has also been prepared using monofunctionalized terephthalate
      linkers containing -NH(2) and -NO(2) groups. The structure of Sc(2)(NH(2)-BDC)(3)
      has been determined by Rietveld analysis of synchrotron powder diffraction at 100
      and 298 K and found to be orthorhombic at both temperatures, whereas the
      structure of Sc(2)(NO(2)-BDC)(3) has been determined by single crystal
      diffraction at 298 K and Rietveld analysis of synchrotron powder diffraction at
      100, 298, 373, and 473 K and is found to be monoclinic at all temperatures.
      Partial ordering of functional groups is observed in each structure. CO(2)
      adsorption at 196 and 273 K indicates that whereas Sc(2)BDC(3) has the largest
      capacity, Sc(2)(NH(2)-BDC)(3) shows the highest uptake at low partial pressure
      because of strong -NH(2)...CO(2) interactions. Remarkably, Sc(2)(NO(2)-BDC)(3)
      adsorbs 2.6 mmol CO(2) g(-1) at 196 K (P/P(0) = 0.5), suggesting that the -NO(2)
      groups are able to rotate to allow CO(2) molecules to diffuse along the narrow
      channels.

PMID- 21958379
TI  - Characterization of the axon initial segment (AIS) of motor neurons and
      identification of a para-AIS and a juxtapara-AIS, organized by protein 4.1B.
AB  - BACKGROUND: The axon initial segment (AIS) plays a crucial role: it is the site
      where neurons initiate their electrical outputs. Its composition in terms of
      voltage-gated sodium (Nav) and voltage-gated potassium (Kv) channels, as well as
      its length and localization determine the neuron's spiking properties. Some
      neurons are able to modulate their AIS length or distance from the soma in order
      to adapt their excitability properties to their activity level. It is therefore
      crucial to characterize all these parameters and determine where the myelin
      sheath begins in order to assess a neuron's excitability properties and ability
      to display such plasticity mechanisms. If the myelin sheath starts immediately
      after the AIS, another question then arises as to how would the axon be organized
      at its first myelin attachment site; since AISs are different from nodes of
      Ranvier, would this particular axonal region resemble a hemi-node of Ranvier?
      RESULTS: We have characterized the AIS of mouse somatic motor neurons. In
      addition to constant determinants of excitability properties, we found
      heterogeneities, in terms of AIS localization and Nav composition. We also
      identified in all alpha motor neurons a hemi-node-type organization, with a
      contactin-associated protein (Caspr)+ paranode-type, as well as a Caspr2+ and
      Kv1+ juxtaparanode-type compartment, referred to as a para-AIS and a juxtapara
      (JXP)-AIS, adjacent to the AIS, where the myelin sheath begins. We found that Kv1
      channels appear in the AIS, para-AIS and JXP-AIS concomitantly with myelination
      and are progressively excluded from the para-AIS. Their expression in the AIS and
      JXP-AIS is independent from transient axonal glycoprotein-1 (TAG-1)/Caspr2, in
      contrast to juxtaparanodes, and independent from PSD-93. Data from mice lacking
      the cytoskeletal linker protein 4.1B show that this protein is necessary to form
      the Caspr+ para-AIS barrier, ensuring the compartmentalization of Kv1 channels
      and the segregation of the AIS, para-AIS and JXP-AIS. CONCLUSIONS: alpha Motor
      neurons have heterogeneous AISs, which underlie different spiking properties.
      However, they all have a para-AIS and a JXP-AIS contiguous to their AIS, where
      the myelin sheath begins, which might limit some AIS plasticity. Protein 4.1B
      plays a key role in ensuring the proper molecular compartmentalization of this
      hemi-node-type region.

PMID- 21958383
TI  - Platelet membrane phospholipid asymmetry: from the characterization of a
      scramblase activity to the identification of an essential protein mutated in
      Scott syndrome.
AB  - Like all eukaryotic cells, platelets maintain plasma membrane phospholipid
      asymmetry in normal blood circulation via lipid transporters, which control
      transbilayer movement. Upon platelet activation, the asymmetric orientation of
      membrane phospholipids is rapidly disrupted, resulting in a calcium-dependent
      exposure of the anionic phospholipid, phosphatidylserine (PS), at the outer
      platelet surface. This newly-exposed PS surface is a major component of normal
      hemostasis because it supports platelet procoagulant function. Binding of blood
      clotting enzyme complexes to this negatively-charged membrane surface allows a
      dramatic increase in the rate of conversion of zymogens to active serine
      proteases, which in turn produce a burst of thrombin leading to the formation of
      a fibrin clot and further platelet activation. Cells have the capacity to
      catalyze transbilayer phospholipid exchange via ATP-requiring translocase enzymes
      (flippases and floppases), which control unidirectional phospholipid transport
      against a concentration gradient. They also use an energy-independent, calcium
      dependent scramblase activity to govern the bidirectional exchange of
      phospholipids between the two leaflets of the bilayer; this activity is essential
      for PS exposure during platelet activation. Scramblase activity, biochemically
      characterized in the 1980s, is deficient in patients with Scott syndrome, a rare
      inherited bleeding disorder with defective platelet procoagulant activity.
      Despite considerable efforts, the platelet scramblase protein remained elusive
      for years but a significant advance has recently been made with the
      identification of TMEM16F, a membrane protein essential for calcium-dependent PS
      exposure whose loss of function mutations are found in Scott syndrome. This
      review recalls historical aspects of platelet membrane asymmetry
      characterization, summarizes the mechanisms and roles of PS exposure following
      platelet activation and discusses the recent identification of TMEM16F and its
      significance in the scrambling process.

PMID- 21958384
TI  - Analysis of euphornin in Euphorbia helioscopia L. and its cytotoxicity to mice
      lung adenocarcinoma cells (LA795).
AB  - Euphorbia helioscopia L. has been used as a herbal remedy for cancer in mainland
      China. Euphornin is one of the main bioactive constituents with the maximal
      content of Euphorbia helioscopia L. A reversed-phase high-performance liquid
      chromatography method with evaporative light scattering detection (ELSD) was
      developed for the analysis of euphornin for better quality control of E.
      helioscopia L. A good calibration curve in double logarithmic coordinator for
      euphornin was obtained. The validation study showed high recoveries (>97.0%) and
      low coefficient of variation (<3.0%). The use of the method on different
      euphornin extract samples confirmed its effectiveness. It was shown that ELSD was
      an effective detection method for the analysis of the non-volatile diterpenes
      from plants used in traditional Chinese medicine. The evaluation of the
      cytotoxicity of euphornin to mice lung adenocarcinoma cells (LA795) suggested
      that euphornin was one of the constituents of E. helioscopia L. responsible for
      the cytotoxicity against carcinoma cells.

PMID- 21958385
TI  - Phlorotannin production and lipid oxidation as a potential protective function
      against high photosynthetically active and UV radiation in gametophytes of Alaria
      esculenta (Alariales, Phaeophyceae).
AB  - Radiation damage can inter alia result in lipid peroxidation of macroalgal cell
      membranes. To prevent photo-oxidation within the cells, photoprotective
      substances such as phlorotannins are synthesized. In the present study, changes
      in total fatty acids (FA), FA composition and intra/extracellular phlorotannin
      contents were determined by gas chromatography and the Folin-Ciocalteu method to
      investigate the photoprotective potential of phlorotannins to prevent lipid
      peroxidation. Alaria esculenta juveniles (Phaeophyceae) were exposed over 20 days
      to high/low photosynthetically active radiation (PAR) in combination with UV
      radiation (UVR) in the treatments: PAB (low/high PAR + UV-B + UV-A), PA (low/high
      PAR + UV-A) or low/high PAR only. While extracellular phlorotannins increased
      after 10 days, intracellular phlorotannins increased with exposure time and PA
      and decreased under PAB. Interactive effects of time:radiation wavebands,
      time:PAR dose as well as radiation wavebands:PAR dose were observed. Low FA
      contents were detected in the PA and PAB treatments; interactive effects were
      observed between time:high PAR and PAB:high PAR. Total FA contents were
      correlated to extra/intracellular phlorotannin contents. Our results suggest that
      phlorotannins might play a role in intra/extracellular protection by absorption
      and oxidation processes. Changes in FA content/composition upon UVR and high PAR
      might be considered as an adaptive mechanism of the A. esculenta juveniles
      subjected to variations in solar irradiance.

PMID- 21958386
TI  - Highly fluorescent GFPm 2+ -based genome integration-proficient promoter probe
      vector to study Mycobacterium tuberculosis promoters in infected macrophages.
AB  - Study of activity of cloned promoters in slow-growing Mycobacterium tuberculosis
      during long-term growth conditions in vitro or inside macrophages, requires a
      genome-integration proficient promoter probe vector, which can be stably
      maintained even without antibiotics, carrying a substrate-independent, easily
      scorable and highly sensitive reporter gene. In order to meet this requirement,
      we constructed pAKMN2, which contains mycobacterial codon-optimized gfp(m) (2+)
      gene, coding for GFP(m) (2+) of highest fluorescence reported till date,
      mycobacteriophage L5 attP-int sequence for genome integration, and a multiple
      cloning site. pAKMN2 showed stable integration and expression of GFP(m) (2+) from
      M. tuberculosis and M. smegmatis genome. Expression of GFP(m) (2+), driven by the
      cloned minimal promoters of M. tuberculosis cell division gene, ftsZ (MtftsZ),
      could be detected in the M. tuberculosis/pAKMN2-promoter integrants, growing at
      exponential phase in defined medium in vitro and inside macrophages. Stable
      expression from genome-integrated format even without antibiotic, and high
      sensitivity of detection by flow cytometry and fluorescence imaging, in spite of
      single copy integration, make pAKMN2 useful for the study of cloned promoters of
      any mycobacterial species under long-term in vitro growth or stress conditions,
      or inside macrophages.

PMID- 21958387
TI  - Video calls from lay bystanders to dispatch centers - risk assessment of
      information security.
AB  - BACKGROUND: Video calls from mobile phones can improve communication during
      medical emergencies. Lay bystanders can be instructed and supervised by health
      professionals at Emergency Medical Communication Centers. Before implementation
      of video mobile calls in emergencies, issues of information security should be
      addressed. METHODS: Information security was assessed for risk, based on the
      information security standard ISO/IEC 27005:2008. A multi-professional team used
      structured brainstorming to find threats to the information security aspects
      confidentiality, quality, integrity, and availability. RESULTS: Twenty security
      threats of different risk levels were identified and analyzed. Solutions were
      proposed to reduce the risk level. CONCLUSIONS: Given proper implementation, we
      found no risks to information security that would advocate against the use of
      video calls between lay bystanders and Emergency Medical Communication Centers.
      The identified threats should be used as input to formal requirements when
      planning and implementing video calls from mobile phones for these call centers.

PMID- 21958388
TI  - Frequency-domain investigation of the ionic mobility of triflate salts in
      tetrahydrofuran.
AB  - The frequency-dependent molar conductivities of two triflate salts,
      tetrabutylammonium triflate (TBATf) and lithium triflate (LiTf), in
      tetrahydrofuran are measured in the microwave frequency domain at the
      concentrations where the direct-current molar conductivity increases with
      concentration. The relaxation frequency of the conductivity of TBATf increases
      with concentration as was demonstrated by a simulation and theoretical
      calculation on a simple model system. However, the low-frequency side of the
      relaxation of the conductivity of LiTf grows with increasing concentration,
      suggesting the presence of large aggregates such as triple ions. The molar
      conductivities of both salts at 20 GHz are about an order of magnitude smaller
      than those predicted by the Nernst-Einstein relationship, indicating the
      importance of the picosecond or faster dynamics in the determination of the
      absolute value of the conductivity.

PMID- 21958389
TI  - Life quality of Chinese patients with chronic urticaria as assessed by the
      dermatology life quality index.
AB  - BACKGROUND: No report focused on the life quality of Chinese patients with
      chronic urticaria (CU). It was also due to lack of data to assess the usage of
      the Dermatology Life Quality Index (DLQI) in Chinese patients. OBJECTIVES: We
      explored the quality of life (QoL) of Chinese patients with CU and assessed the
      factor structure and reliability of the Chinese version of the DLQI. METHODS: The
      DLQI scores were recorded to evaluate the life quality of out-patients with CU.
      The reliability and the factor structure of the DLQI were assessed using
      reliability analysis and factor analysis. RESULTS: A total of 131 patients
      completed the DLQI. The mean score was 9.93 that was significantly associated
      with the patient's age (P = 0.01). Chronic urticaria had the greatest effect on
      the 'Syndrome and Feeling' (50.64%), followed by 'Work/School' (41.98%). A
      reliability analysis showed that the value of the Cronbach'salpha reached 0.85 if
      item 1 in the DLQI was excluded. Both exploratory and confirmatory factor
      analysis indicated that there were two latent common factors underlying the items
      in the questionnaire. CONCLUSIONS: Chronic urticaria has a moderate impact on the
      life quality. More attention should be paid to the interference from item 1 in
      assessing the QoL by the DLQI, although it remains a concise tool with high
      reliability.

PMID- 21958390
TI  - Swedish attitudes towards persons with mental illness.
AB  - BACKGROUND: Negative and stigmatizing attitudes towards persons with mental
      illness must be dealt with to facilitate the sufferers' social acceptance. AIM:
      The present study aimed at survey Swedish attitudes towards persons with mental
      illness related to factors impacting these attitudes. MATERIAL AND METHODS: New
      CAMI-S based on the questionnaire "Community Attitudes to Mental Illness in
      Sweden" ([CAMI] Taylor & Dear, 1981) was developed with nine behavioral-intention
      items and thus comprised a total of 29 items. Of 5000 Swedish people, 2391 agreed
      to complete the questionnaire. Principal component analysis rendered four factors
      reflecting attitudes towards the mentally ill: Intention to Interact, Fearful and
      Avoidant, Open-minded and Pro-Integration, as well as Community Mental Health
      Ideology. The factors were analyzed for trends in attitudes. By MANOVA, the
      experience of mental illness effects on mind-set towards the sufferers was
      assessed. By means of logistic regression, demographic factors contributing to
      positive attitudes towards persons with mental illness residing in the
      neighborhood were assessed. RESULTS: By New CAMI-S, the Swedish attitudes towards
      the mentally ill were surveyed and trends in agreement with living next to a
      person with mental illness were revealed in three out of four factors derived by
      principal component analysis. Aspects impacting the Swedish attitudes towards
      persons with mental illness and willingness to have him/her residing in the
      neighborhood comprised experience of mental illness, female gender, age (31-50
      years), born in Scandinavia or outside Europe, only 9 years of compulsory school
      and accommodation in flat. CONCLUSION: The New CAMI-S came out as a useful tool
      to screen Swedish attitudes towards persons with mental illness. Most Swedes were
      prepared to live next to the mentally ill.

PMID- 21958391
TI  - Prospective study on severe malaria among in-patients at Bombo regional hospital,
      Tanga, north-eastern Tanzania.
AB  - BACKGROUND: In Tanzania, malaria is the major cause of morbidity and mortality,
      accounting for about 30% of all hospital admissions and around 15% of all
      hospital deaths. Severe anaemia and cerebral malaria are the two main causes of
      death due to malaria in Tanga, Tanzania. METHODS: This was a prospective
      observational hospital-based study conducted from October 2004 to September 2005.
      Consent was sought from study participants or guardians in the wards. Finger
      prick blood was collected from each individual for thick and thin smears, blood
      sugar levels and haemoglobin estimations by Haemocue machine after admission.
      RESULTS: A total of 494 patients were clinically diagnosed and admitted as cases
      of severe malaria. Majority of them (55.3%) were children below the age of 5
      years. Only 285 out of the total 494 (57.7%) patients had positive blood smears
      for malaria parasites. Adults aged 20 years and above had the highest rate of
      cases with fever and blood smear negative for malaria parasites. Commonest
      clinical manifestations of severe malaria were cerebral malaria (47.3%) and
      severe anaemia (14.6%), particularly in the under-fives. Case fatality was 3.2%
      and majority of the deaths occurred in the under-fives and adults aged 20 years
      and above with negative blood smears. CONCLUSION: Proper laboratory diagnosis is
      crucial for case management and reliable data collection. The non-specific nature
      of malaria symptomatologies limits the use of clinical diagnosis and the IMCI
      strategy. Strengthening of laboratory investigations to guide case management is
      recommended.

PMID- 21958392
TI  - Anti-albuminuric effects of the angiotensin AT1 receptor blocker telmisartan in
      hypertensive patients.
AB  - We evaluated the anti-hypertensive and anti-albuminuric effect of the angiotensin
      receptor blocker telmisartan alone and in combination with torasemide and
      amlodipine. Patients were hypertensive, both diabetics and non-diabetics with
      persistent microalbuminuria. Our primary endpoint was a change in
      microalbuminuria levels, while the secondary endpoints were changes in systolic
      blood pressure (SBP), diastolic blood pressure (DBP), serum creatinine levels,
      and glomerular filtration rate.After the 16-week treatment period, the patients
      significantly reduced microalbuminuria levels (76.4 +/- 52.4 MUg/min; p < 0.001),
      SBP (16.4 +/- 8.7 mmHg; p < 0.001) and DBP (17.7 +/- 5.9 mmHg; p < 0.001). Both
      diabetics and non-diabetics showed an identical pattern of significance with
      respect to the whole population. Systolic blood pressure, DBP, and
      microalbuminuria were significantly reduced as a consequence of therapy, both in
      diabetics and non-diabetics.

PMID- 21958394
TI  - Enamine carboxylates as stereodetermining intermediates in prolinate catalysis.
AB  - Experimental and computational studies probing the nature of intermediates in the
      alpha-amination of aldehydes catalyzed by prolinate salts support an enamine
      carboxylate intermediate in the stereodetermining step.

PMID- 21958393
TI  - Anthropometric indices of central obesity how discriminators of metabolic
      syndrome in Brazilian women with polycystic ovary syndrome.
AB  - BACKGROUND: Central obesity is highly prevalent in women with polycystic ovary
      syndrome (PCOS) and is strongly associated with metabolic syndrome (MetS).
      OBJECTIVES: To define cut-off points of waist circumference (WC), waist-to-height
      ratio (WHtR), waist-to-hip ratio (WHR), and conicity index (C-Index) to
      discriminate metabolic syndrome (MetS) in Brazilian women with PCOS. METHODS: In
      a cross-sectional study, anthropometric, biochemical and clinical parameters were
      measured in 113 Brazilian PCOS women (27.2 +/- 4.5 years). Receiver operating
      characteristic (ROC) analysis was used to find out the cut-off points of
      anthropometric indices to predict MetS according with National Cholesterol
      Education Program Adult Treatment Panel III (NCEP ATP-III) criteria. RESULTS:
      Considering the ROC curve analysis the WC and WHtR had a similar performance in
      predicting MetS and these parameters were better than WHR and C-Index. The
      optimal cut-off values of the anthropometric indices for discriminate MetS were:
      WC = 95 cm; WHtR = 0.59; WHR = 0.88; and C-Index = 1.25. By using these cut-off
      points the sensitivity and specificity rates of WC and WHtR were higher than
      those observed for WHR and C-Index. CONCLUSION: Our results indicated that WC and
      WHtR are more accurate than WHR and C-Index to predict MetS in Brazilian PCOS
      women.

PMID- 21958395
TI  - Curcumin is a potent modulator of microglial gene expression and migration.
AB  - BACKGROUND: Microglial cells are important effectors of the neuronal innate
      immune system with a major role in chronic neurodegenerative diseases. Curcumin,
      a major component of tumeric, alleviates pro-inflammatory activities of these
      cells by inhibiting nuclear factor kappa B (NFkB) signaling. To study the immuno
      modulatory effects of curcumin on a transcriptomic level, DNA-microarray analyses
      were performed with resting and LPS-challenged microglial cells after short-term
      treatment with curcumin. METHODS: Resting and LPS-activated BV-2 cells were
      stimulated with curcumin and genome-wide mRNA expression patterns were determined
      using DNA-microarrays. Selected qRT-PCR analyses were performed to confirm newly
      identified curcumin-regulated genes. The migration potential of microglial cells
      was determined with wound healing assays and transwell migration assays.
      Microglial neurotoxicity was estimated by morphological analyses and
      quantification of caspase 3/7 levels in 661W photoreceptors cultured in the
      presence of microglia-conditioned medium. RESULTS: Curcumin treatment markedly
      changed the microglial transcriptome with 49 differentially expressed transcripts
      in a combined analysis of resting and activated microglial cells. Curcumin
      effectively triggered anti-inflammatory signals as shown by induced expression of
      Interleukin 4 and Peroxisome proliferator activated receptor alpha. Several novel
      curcumin-induced genes including Netrin G1, Delta-like 1, Platelet endothelial
      cell adhesion molecule 1, and Plasma cell endoplasmic reticulum protein 1, have
      been previously associated with adhesion and cell migration. Consequently,
      curcumin treatment significantly inhibited basal and activation-induced migration
      of BV-2 microglia. Curcumin also potently blocked gene expression related to pro
      inflammatory activation of resting cells including Toll-like receptor 2 and
      Prostaglandin-endoperoxide synthase 2. Moreover, transcription of NO synthase 2
      and Signal transducer and activator of transcription 1 was reduced in LPS
      triggered microglia. These transcriptional changes in curcumin-treated LPS-primed
      microglia also lead to decreased neurotoxicity with reduced apoptosis of 661W
      photoreceptor cultures. CONCLUSIONS: Collectively, our results suggest that
      curcumin is a potent modulator of the microglial transcriptome. Curcumin
      attenuates microglial migration and triggers a phenotype with anti-inflammatory
      and neuroprotective properties. Thus, curcumin could be a nutraceutical compound
      to develop immuno-modulatory and neuroprotective therapies for the treatment of
      various neurodegenerative disorders.

PMID- 21958396
TI  - Body mass index percentiles for Turkish children aged 0-84 months.
AB  - BACKGROUND: Reference body mass index (BMI) percentiles are needed to follow
      secular changes in Turkish children aged 0-84 months. Obesity prevalence in this
      age group is also not well documented. AIM: The aim of this study was to
      determine BMI percentiles and the prevalences of overweight and obesity in
      Turkish children aged 0-84 months. The authors also tried to compare actual BMI
      status with World Health Organization (WHO) standards. SUBJECTS AND METHODS: This
      study used data from the Anthropometry of Turkish Children aged 0-6 years (ATCA
      06) study. This cross-sectional study, conducted from September 2009 to May 2010
      in Kayseri, Turkey, included 2683 children (1359 girls, 1324 boys) aged 0-84
      months. Centile curves were constructed using the LMS method. RESULTS: It was
      found that BMI percentiles of Turkish children were higher than WHO standards in
      early childhood. The overweight and obesity prevalences were identical in both
      genders, 10.0% and 4.9%, respectively. CONCLUSION: This study provides both BMI
      reference values and prevalence figures for overweight and obesity in children
      aged 0-84 months, residing in Kayseri city, in Turkey. It is believed that these
      data can be of use in following secular changes as well as for comparisons with
      international standards.

PMID- 21958397
TI  - World view and a farewell.

PMID- 21958398
TI  - Primary care and specialty care delays in diagnosing Trichophyton verrucosum
      infection related to cattle exposure.
AB  - The objective of this study was to identify exposure risks, body site of
      presentation, length of time from symptom onset to definitive diagnosis, initial
      and eventual treatment courses, and the number of medical visits between initial
      assessment and definitive diagnosis for patients with culture-proven Trichophyton
      verrucosum (T. verrucosum) skin infection, and to report the specialties of
      physicians making the initial assessment and the eventual correct diagnosis.
      Chart data were abstracted from patients diagnosed with culture-proven T.
      verrucosum in the Marshfield Clinic system from May 1996 to August 2009. Fifty
      one patients were identified and included in the study. Of the 51 patients
      studied, 39 had a documented history of cattle exposure. The average length of
      time from symptom onset to diagnosis was 41.5 days. Prior to a culture-positive
      T. verrucosum diagnosis, 35 patients were treated with topical medications, 10
      received oral antibiotics, and 6 received no initial treatment. After a culture
      positive T. verrucosum diagnosis was obtained, all documented treatments were
      either oral or topical antifungal medications. In 68.6% of cases, the physician
      making the initial assessment was different than the physician making the final
      diagnosis. Health care providers who care for patients in rural populations
      presenting with recalcitrant inflammatory skin lesions should include
      occupational and exposure histories and include cutaneous fungal infections in
      the differential diagnosis of chronic inflammatory skin lesions, particularly in
      patients with a history of contact with cattle. Fungal cultures may aid in the
      definitive diagnosis when cattle ringworm is suspected. Increased awareness of
      the condition among all care providers may decrease the number of medical visits
      required, avoid unnecessary drug therapy, shorten the time to make the correct
      diagnosis, and hasten the onset of appropriate antifungal therapy.

PMID- 21958399
TI  - Depressive symptoms and sleepiness among Latino farmworkers in eastern North
      Carolina.
AB  - Depression and sleepiness are both risk factors for occupational accidents and
      unintentional injury. Relatively little is known about the experiences of these
      risk factors in the immigrant Latino farmworker population. This analysis uses
      prospective panel data from a sample of Latino farmworkers in eastern North
      Carolina that were collected at monthly intervals during the 2008 agricultural
      season to (1) describe depressive symptoms and daytime sleepiness among immigrant
      Latino farmworkers across the agricultural season; (2) delineate associations of
      depressive symptoms with sleepiness across time; and (3) determine whether
      depressive symptoms precede sleepiness, or if sleepiness precedes depressive
      symptoms. Results indicated that 45% of farmworkers experienced elevated
      depressive symptoms across the season, whereas 20% experienced elevated
      sleepiness. Elevated depressive symptoms were more common among farmworkers
      living in barracks, and less common among those living in trailers. Sleepiness
      was more common among women than men. There was no evidence that depressive
      symptoms contributed to sleepiness, or that sleepiness contributed to depressive
      symptoms. The pattern of results suggests that a substantial proportion of Latino
      farmworkers experience levels of depressive symptoms or sleepiness that places
      them at risk for occupational accident or unintentional injury. The results also
      suggest that depressive symptoms and sleepiness do not cause each other; rather,
      the association of depressive symptoms with sleepiness hints at the possibility
      of a common physiologic mechanism such as circadian disruption.

PMID- 21958400
TI  - A task-based analysis of machinery entanglement injuries among Western Canadian
      farmers.
AB  - Machinery entanglements are a leading cause of hospitalized injury on Canadian
      farms. This study evaluates the role farm tasks play in the occurrence of
      machinery entanglement events. A retrospective case series of 41 entanglement
      injuries involving 35 farm-machinery types was assembled. Only a few limited
      tasks were implicated in the majority of entanglements. These tasks were as
      follows: (1) field adjustments of machinery; (2) product handling and conveyance;
      and (3) driveline attachments and servicing. Hazards inherent and common to these
      tasks affected the behavior of farmers, leading to entanglements. This study
      establishes a need to identify hazards and assess risks associated with different
      tasks involving the use of farm machinery under actual field situations. Systemic
      changes are required to improve existing machinery safety practices through
      engineering, work methods, and work practice modifications. In addition to design
      solutions, occupational health and safety strategies should consider activities
      associated with hazardous situations to inform the content of injury prevention
      efforts.

PMID- 21958401
TI  - Size distribution of particulate and associated endotoxin and bacteria in
      traditional swine barn rooms and rooms sprinkled with oil.
AB  - The objective of this pilot study was to investigate if a once-a-day sprinkling
      of canola oil in a swine confinement facility alters the airborne concentration
      and distribution of particulate matter and associated compounds (endotoxin and
      culturable microbes). Particulate was collected using an eight-stage cascade
      impactor in four identical swine grower/finisher rooms of a swine barn.
      Particulate (mg/m(3)) and endotoxin (EU/m(3) and EU/mg) distribution was
      determined. A six-stage viable cascade impactor was used to quantify total
      bacteria, enteric bacteria, and fungi. Microbes were characterized from
      subcultures prepared from the 10 most predominant colony types on each stage 3
      (aerodynamic size 3.3-4.7MUm) of the collection plates. Results indicated that
      oil sprinkling reduced total dust by 86% and total endotoxin concentration by
      82.5%. However, the distribution patterns indicate that reduction is observed
      predominantly on large dust particles. In addition, the proportion of endotoxin
      associated with smaller particulate sizes (i.e., particles <4.7 MUm) was higher
      in the oil-sprinkled rooms. Oil sprinkling does not markedly alter distribution
      of total bacteria, enteric bacteria, or fungi. The most frequently identified
      species were gram-positive genera. Oil sprinkling in swine confinement
      grower/finisher rooms can significantly reduce airborne total dust and endotoxin;
      however, smaller particles and associated endotoxin appear to remain in
      suspension, suggesting the overall improvement in air quality is uncertain.
      Further distribution studies and exposure outcome studies would need to be
      undertaken to determine the impacts of oil sprinkling.

PMID- 21958403
TI  - Agricultural health and safety performance in Australia.
AB  - This study aimed to determine the proportion of Australian farming enterprises
      with systems and processes that meet current regulatory and industry standards
      for health and safety. Data from 683 farming enterprises were drawn from a
      nationally stratified random sample representing seven commodity sectors: beef
      cattle, cotton, dairy, horticulture, grain growing, sheep, and sugar cane.
      Results indicated low levels of implementation for farm health and safety plans
      as well as induction for new workers and contractors. Improvements to control
      major safety hazards are required for farm machinery and implements, farm
      vehicles, reducing exposure of children to hazards, and the use of helmets when
      riding quad bikes, motorbikes, and horses. There were considerable variations
      between commodity sectors. There remains significant scope to enhance the safety
      of farmers in Australia.

PMID- 21958402
TI  - Potential of a quarter individual milking system to reduce the workload in large
      herd dairy operations.
AB  - Large-herd dairy operations utilize parlor milking systems that reduce the
      physical workload in comparison to tethering systems. Nevertheless, the number of
      musculoskeletal disorders among workers on dairy farms is not decreasing. In
      response, a study was carried out to measure the workload focusing on the impact
      of working height and weight of the milking unit. In this article a new quarter
      individual milking unit without claw and using single-tube guidance is compared
      with a light (1.4 kg) conventional unit. A significant reduction of muscular load
      as well as the reduction of process time was measured using the quarter
      individual system. Body posture was also recorded using video-based motion
      analysis. Based on these results, the new system is expected to significantly
      improve the work place in modern milking parlors by reducing extreme postures as
      well as the physical and static musculoskeletal load.

PMID- 21958404
TI  - Behavioral and nonbehavioral risk factors for occupational injuries and health
      problems among Belgian farmers.
AB  - Preventive interventions to reduce occupational injuries and diseases among
      farmers require an appraisal of the relative importance of the various risk
      factors. This paper describes the results of a cross-sectional study
      investigating determinants of occupational health and injuries among 510 Belgian
      farmers, looking at health-related behaviors (machinery use, animal handling,
      fall prevention, and pesticide use), as well as nonbehavioral risk factors
      (demographic characteristics, farm characteristics, and participation in safety
      training). Education level and number of employees on the farm were identified as
      nonbehavioral risk factors for injuries, with highly educated farmers and working
      with one employee associated with a higher injury risk. In contrast, none of the
      nonbehavioral factors were related to occupational disease. Unsafe machinery use,
      animal handling, fall prevention, and pesticide use were behavioral risk factors
      for injuries, with unsafe pesticide use representing the highest risk. Unsafe
      machinery and pesticide use were also risks for disease. Significant differences
      in self-reported behavior were found for gender, age, number of employees, and
      the interaction between age and education. The study highlights the importance of
      behavioral factors as determinants of occupational injuries and diseases among
      farmers, and suggests that tailored preventive interventions should be developed
      to accommodate for differences in these behaviors among subgroups of farmers.

PMID- 21958405
TI  - Proceedings of the "Arthritis, Agriculture, and Rural Life: state of the art
      research, practices, and applications" conference, West Lafayette, Indiana, May
      11-13, 2011.
AB  - This article presents proceedings of the first national conference to assemble
      professionals to address the issue of arthritis in agriculture. The "Arthritis,
      Agriculture, and Rural Life: State of the Art Research, Practices, and
      Applications" conference, May 11-13, 2011, at the Purdue University Beck
      Agricultural Center in West Lafayette, Indiana, focused on increasing awareness
      and education in the prevention, effects, care, and treatment of arthritis
      specific to farmers. Presentations included a contextualizing keynote and
      sessions addressing the prevention and treatment of arthritis in agriculture,
      including topics such as traditional arthritis therapies, alternative treatments,
      assistive technology, and ergonomic techniques and modifications. Participants
      discussed particular issues on a field trip to several Purdue University research
      farms addressing ergonomics. The conference concluded with a farmer panel, where
      attendees heard personal stories from farmers suffering from the effects of
      arthritis.

PMID- 21958410
TI  - Immune-related genes expression profile in orange-spotted grouper during exposure
      to Cryptocaryon irritans.
AB  - Cryptocaryon irritans is one of the most important ectoparasites of marine fish.
      To identify the potential role of immune-related genes in antiparasitic immune
      responses in fish, we monitored the expression change of IL-8, COX-2, C-type
      lectin and transferrin in local and systemic immune organs of orange-spotted
      grouper post-C. irritans infection. IL-8 expression was up-regulated during the
      course of infection in the skin, while COX-2 and transferrin expression was up
      regulated in the gill. COX-2 expression was significantly down-regulated in the
      spleen (0.7-5% of its control) and head kidney (0.5-4% of its control) post
      primary infection. Transferrin expression was also down-regulated in the spleen
      and head kidney from 6 h to 5 days post-primary infection. However, C-type lectin
      expression was up-regulated in all tested organs post-infection, with the
      exception of day 7 in the spleen post-primary infection where the expression
      level was slightly down-regulated (44% of its control). These results suggest
      that these four immune-related genes play an important role in grouper anti-C.
      irritans infection and that local immune organs as the active organs contribute
      more than systemic immune organs to this course.

PMID- 21958411
TI  - Dissolution parameters reveal role of structure and solvent in molecular
      gelation.
AB  - The relationship between thermodynamic dissolution parameters (enthalpy and
      entropy) and gelation ability was examined for two different classes of compounds
      in three different solvent systems. In total, 11 dipeptides and 19 pyridines were
      synthesized and screened for gelation in aqueous and organic solvents,
      respectively. The dissolution parameters were determined from the variable
      temperature solubilities using the van't Hoff equation. These studies revealed
      that the majority of gelators had higher dissolution enthalpies and entropies
      compared to nongelators, consistent with the notion that gelators have stronger
      intermolecular interactions and more order in the solid state. The dissolution
      parameters were also found to be solvent-dependent, suggesting that solvent
      solute interactions are also important in gelation. Overall, these results
      indicate that converting nongelators into gelators is attainable when structural
      modifications or a change in solvent lead to increases in the dissolution
      parameters.

PMID- 21958413
TI  - Tris(triazolyl) calix[6]arene-based zinc and copper funnel complexes: imidazole
      like or pyridine-like? A comparative study.
AB  - Huisgen dipolar cycloaddition leads straightforwardly to new funnel complexes
      based on the calix[6]arene macrocycle bearing three functionalized triazoles as
      coordinating units at the small rim. Coordination to Zn(II) and Cu(I) cations was
      studied using (1)H NMR and IR spectroscopies and cyclic voltammetry. The nature
      of the substituents on the triazole ring affects the behavior of the ligands and
      their coordinating ability and controls the host-guest properties of the metal
      receptors for exogenous substrates. Depending on their substitution pattern but
      also on the metal ion and the guest ligand, the triazole-based systems behave
      either imidazole-like or pyridine-like. The ease of preparation and the
      versatility of 1,4-disubstituted-1,2,3-triazoles with tunable steric and
      electronic properties make them promising candidates for further applications
      from biology to materials.

PMID- 21958415
TI  - Maternal obesity predict isolated birth defects in live births in Eastern
      Province of Saudi Arabia.
AB  - OBJECTIVE: There is no research on the predictors of birth defects in Al Ahsa
      Governorate in the Eastern Province of Saudi Arabia. The aim of this research was
      to detect the predictors of isolated structural birth defects in live births.
      METHODS: We conducted this study from April 2006 to 2010. Live births with
      isolated birth defects represented our sample for this retrospective case control
      study. Univariate analysis was done for all possible risk factors. Logistic
      regression analysis was done for all predictors in relation to different birth
      defects. RESULTS: Out of 37168 live births, isolated structural birth defects
      were found in 318 cases. Obesity ( body mass index > 30) was a significant
      predictor for increased nervous system anomalies ( odds ratio (OR): 7.83, CI: 3.9
      15.4), facial defects (OR: 5.92, CI: 2.8-12.4), genitourinary anomalies (OR: 4.6
      CI: 1.9-11.1), and cardiac malformations (OR: 2.7 CI: 1.3-5.7). Consanguinity
      increased the risk for cardiac malformations (OR: 3.32, CI: 1.54-7.17). Low socio
      economic status increased the risk for nervous system anomalies (OR: 2.09, CI:
      1.18-3.7), facial defects (OR: 2.33, CI: 1.25-4.33) and musculoskeletal anomalies
      (OR: 2.3, CI: 1.29-4.09). CONCLUSION: Maternal obesity represented the most
      common predictor for certain categories of isolated structural birth defects
      including nervous system, facial, genitourinary and cardiac.

PMID- 21958414
TI  - Molecular cloning and characterization of the STAT gene in Hyphantria cunea
      haemocytes.
AB  - A new insect member of the signal transducer and activator of transcription
      (STAT) family of transcription factors, Hyphantria cunea STAT (HcSTAT), was
      cloned from the lepidopteran H. cunea. The domain involved in DNA interaction and
      the Src homology 2 (SH2) domain were well conserved. During all developmental
      stages, the gene was expressed at a low level in the haemocytes, fat body cells,
      midgut, epidermis and Malpighian tubules. The haemocytes and Malpighian tubules
      showed transcriptional activation of HcSTAT upon Gram-negative and Gram-positive
      bacterial challenges. These challenges increased the induction and nuclear
      translocation of the HcSTAT protein that recognizes a STAT target site in H.
      cunea haemocytes. In vivo treatment with sodium orthovanadate translocated HcSTAT
      to the haemocyte nucleus. This study shows the involvement of the haemocyte Janus
      kinase/STAT pathway after microbial infection in lepidopteran insects.

PMID- 21958426
TI  - Tris(oxazolinyl)boratomagnesium-catalyzed cross-dehydrocoupling of organosilanes
      with amines, hydrazine, and ammonia.
AB  - We report magnesium-catalyzed cross-dehydrocoupling of Si-H and N-H bonds to give
      Si-N bonds and H(2). A number of silazanes are accessible using this method, as
      well as silylamines from NH(3) and silylhydrazines from N(2)H(4). Kinetic studies
      of the overall catalytic cycle and a stoichiometric Si-N bond-forming reaction
      suggest nucleophilic attack by a magnesium amide as the turnover-limiting step.

PMID- 21958424
TI  - Maximum probability domains in crystals: the rock-salt structure.
AB  - The present paper studies MX crystals in rock-salt structure (M: Li, Na, K; X: F,
      Cl, Br, I). They are often described as being formed by ions. Pictures based on
      quantum mechanical calculations sustain and quantify it. The tools used are (i)
      the Quantum Theory of Atoms in Molecules, (ii) the Electron Localization
      Function, and (iii) the maximization of the probability to find in a spatial
      domain a number of electrons equal to that of the ion under consideration. The
      present paper shows that the images provided by these three different tools to
      analyze the quantum mechanical calculations yield, for these systems, very
      similar results, in the sense that the spatial domains and probability
      distributions are close. While results for the first two methods are already
      present in the literature, the last of the methods is applied for the first time
      to these systems, and details about the method of calculation and program are
      also given.

PMID- 21958420
TI  - Slow solvent relaxation dynamics of nanometer sized reverse micellar systems
      through tryptophan metabolite, kynurenine.
AB  - Exploration of environmental dynamics using intrinsic biological probe tryptophan
      is very important; however, it suffers from various difficulties. An alternative
      probe, kynurenine (KN), has been found to be an efficient probe for the ultrafast
      dynamics in the biological environment (Goswami et al., [2010] J. Phys. Chem. B.,
      114, 15236-15243). In the present study, we have investigated the efficacy of KN
      for the exploration of relatively slower dynamics of biologically relevant
      environments. A detailed investigation involving UV-Vis, steady-state/time
      resolved fluorescence spectroscopy and Forster resonance energy transfer (FRET)
      studies on KN compared to a well-known solvation probe, H33258, a DNA-minor
      groove binder in a model nonionic reverse micelle reveals that ultrafast internal
      conversion associated with the hydrogen-bonding dynamics masks KN to become a
      dynamical reporter of the immediate environments of the probe.

PMID- 21958421
TI  - Bioconversion of paper sludge to biofuel by simultaneous saccharification and
      fermentation using a cellulase of paper sludge origin and thermotolerant
      Saccharomyces cerevisiae TJ14.
AB  - BACKGROUND: Ethanol production from paper sludge (PS) by simultaneous
      saccharification and fermentation (SSF) is considered to be the most appropriate
      way to process PS, as it contains negligible lignin. In this study, SSF was
      conducted using a cellulase produced from PS by the hypercellulase producer,
      Acremonium cellulolyticus C-1 for PS saccharification, and a thermotolerant
      ethanol producer Saccharomyces cerevisiae TJ14 for ethanol production. Using
      cellulase of PS origin minimizes biofuel production costs, because the culture
      broth containing cellulase can be used directly. RESULTS: When 50 g PS organic
      material (PSOM)/l was used in SSF, the ethanol yield based on PSOM was 23% (g
      ethanol/g PSOM) and was two times higher than that obtained by a separate
      hydrolysis and fermentation process. Cellulase activity throughout SSF remained
      at around 60% of the initial activity. When 50 to 150 g PSOM/l was used in SSF,
      the ethanol yield was 21% to 23% (g ethanol/g PSOM) at the 500 ml Erlenmeyer
      flask scale. Ethanol production and theoretical ethanol yield based on initial
      hexose was 40 g/l and 66.3% (g ethanol/g hexose) at 80 h, respectively, when 161
      g/l of PSOM, 15 filter paper units (FPU)/g PSOM, and 20% inoculum were used for
      SSF, which was confirmed in the 2 l scale experiment. This indicates that PS is a
      good raw material for bioethanol production. CONCLUSIONS: Ethanol concentration
      increased with increasing PSOM concentration. The ethanol yield was stable at
      PSOM concentrations of up to 150 g/l, but decreased at concentrations higher than
      150 g/l because of mass transfer limitations. Based on a 2 l scale experiment,
      when 1,000 kg PS was used, 3,182 kFPU cellulase was produced from 134.7 kg PS.
      Produced cellulase was used for SSF with 865.3 kg PS and ethanol production was
      estimated to be 51.1 kg. Increasing the yeast inoculum or cellulase concentration
      did not significantly improve the ethanol yield or concentration.

PMID- 21958412
TI  - Role of aldehyde dehydrogenase 2 Glu504lys polymorphism in acute coronary
      syndrome.
AB  - This study aimed to investigate the association of the aldehyde dehydrogenase 2
      (ALDH2) Glu504Lys polymorphism, which exists in 30-50% of East Asians, and risk
      of acute coronary syndrome (ACS). We enrolled 1092 unrelated Han Chinese,
      including 546 with ACS and 546 age- and sex-matched controls. Subjects with ALDH2
      mutant genotypes showed significantly higher ACS than did controls (46.7% versus
      31.9%, P < 0.001). Logistic regression analysis revealed the ALDH2 mutant
      independently associated with ACS (odds ratio [OR] 1.95, 95% confidence interval
      [CI]: 1.31-2.92, P = 0.001), but the association was weaker on adjusting for
      alcohol consumption (OR 1.82, 95% CI: 1.23-2.70, P = 0.003). Similar results were
      found in a subgroup analysis of patients with primary ST-segment elevation
      myocardial infarction (STEMI). The ALDH2 mutant was significantly associated with
      level of high-sensitivity C-reactive protein (hs-CRP) in patients with ACS (P =
      0.002) and in controls (P = 0.009) and number of circulating endothelial
      progenitor cells (EPCs) (P = 0.032); furthermore, inclusion of hs-CRP level and
      EPCs number as independent variables in regression analysis reduced the
      importance of ALDH2 polymorphism in ACS or primary STEMI. However, ALDH2
      polymorphism was not associated with number of coronary arteries with significant
      stenosis, Gensini score or flow-mediated dilation of the brachial artery. Our
      results suggest that ALDH2 mutation is a genetic risk marker for ACS, which is
      explained in part by alcohol consumption, inflammation and number of circulating
      EPCs.

PMID- 21958425
TI  - Pilot study on reflectance confocal microscopy imaging of lichen planus: a real
      time, non-invasive aid for clinical diagnosis.
AB  - BACKGROUND: Lichen planus (LP) represents a relatively common skin inflammatory
      entity included in the major group of interface dermatitis. In recent years,
      reflectance confocal microscopy has demonstrated to be a valuable tool for the
      'in vivo' characterization of various skin diseases with cellular level
      resolution. No data are currently available that uses reflectance confocal
      microscopy to study LP. OBSERVATIONS: In this study, we have investigated the
      clinical and confocal features of five cases of histopathologically proven LP,
      and we have correlated the observed features with histopathological findings. The
      most characteristic criterion was the presence of interface dermatitis. Papillary
      rims, usually visible in normal skin, were obscured by the presence of a diffuse
      inflammatory cells infiltrate, arranged in sheet-like structures that surrounded
      the junction almost completely. There was an almost total obliteration of the
      ring-like structures around DP, which appeared non-edged and non-rimmed. Granular
      cells appeared as very large, polygonal structures, with an evident grainy
      cytoplasm, with the transition between spinous and granular cells being clearly
      recognizable, and this feature corresponded to hypergranulosis in histology. The
      presence of inflammatory cells at the level of the epidermis was seen as round-to
      polygonal bright structures in the context of a variable degree of epidermal
      disarray and spongiosis. Melanophages in dermis were visible as brightly
      refractile, plump, oval to stellate-shaped cells. Prominent round or linear dark
      canalicular structures corresponded to dilated blood vessels in the superficial
      dermis on histopathology and appeared horizontally oriented in confocal sections.
      CONCLUSIONS: Reflectance confocal microscopy may represent a real-time, non
      invasive aid to clinical diagnosis of LP. However, it might be difficult to
      distinguish between different subtypes of interface dermatitis. Further research,
      including larger case series, will better define a possible differential
      diagnosis of these diseases using confocal microscopy.

PMID- 21958422
TI  - Management of uncomplicated malaria in children under 13 years of age at a
      district hospital in Senegal: from official guidelines to usual practices.
AB  - BACKGROUND: To be effective, national malaria guidelines must be properly
      followed. This study evaluated nurses' practices in the management of
      uncomplicated malaria cases at a District Hospital. Its objective was to identify
      the reasons for discrepancies between official guidelines and usual practices.
      METHODS: This study took place at Oussouye hospital, south-western Senegal. Blood
      smears were available for biological diagnosis in patients aged more than five
      years while the Integrated Management of Childhood Illness recommended treating
      fevers presumptively in children under five. First line anti-malarial was
      Amodiaquine plus sulphadoxine-pyrimethamine (AQ+SP) bi-therapy. Hospital records
      of children under 13 years of age seen between 2004 and 2005 were reviewed.
      RESULTS: Among children treated with anti-malarials, 74% (2, 063/2, 789) received
      AQ+SP. However, only 22% (406/1, 879) of febrile children and 19% (429/2, 198) of
      children diagnosed with malaria got a blood smear. Moreover, an anti-malarial was
      prescribed for 80% (377/474) of children with a negative blood smear.
      CONCLUSIONS: The transition from chloroquine to AQ+SP was well followed.
      Nonetheless, blood smear use was very low and many over-prescriptions were
      reported. Reasons for discrepancies between guidelines and practices can be
      classified in three main categories: ambiguous guidelines, health system's
      dysfunctions and nurses' own considerations. Aside from the strengthening of the
      public health system, in order to guarantee practices complying with guidelines,
      training content should be more adapted to nurses' own considerations.

PMID- 21958419
TI  - Rightward bias in right hemisphere infarct patients with or without thrombolytic
      treatment and in healthy controls.
AB  - Right hemisphere (RH) infarct patients have a tendency to begin visual scanning
      from the right side of a given stimulus. Our aim was to find out whether RH
      patients with (T+) or without (T-) thrombolytic treatment and healthy controls
      differ in their starting points in three cancellation tasks. Our sample comprised
      of 77 patients and 62 controls. Thirty-four patients received thrombolysis.
      Rightward orientation bias was more evident in the T- group than in the T+ group.
      The T+ group showed a robust tendency to start all cancellation tasks more often
      on the right side than the controls. Regardless of whether they had visual
      neglect, patients in the T+ group showed still defective rightward orienting,
      possibly indicating residual attentional problems. The analyses of starting
      points in visual cancellation tasks provide additional information on residual
      symptoms of attention difficulties after stroke.

PMID- 21958427
TI  - Genomic and phenotypic analysis of BRCA2 mutated breast cancers reveals co
      occurring changes linked to progression.
AB  - BACKGROUND: Inherited mutations in the BRCA2 gene greatly increase the risk of
      developing breast cancer. Consistent with an important role for BRCA2 in error
      free DNA repair, complex genomic changes are frequently observed in tumors
      derived from BRCA2 mutation carriers. Here, we explore the impact of DNA copy
      number changes in BRCA2 tumors with respect to phenotype and clinical staging of
      the disease. METHODS: Breast tumors (n = 33) derived from BRCA2 999del5 mutation
      carriers were examined in terms of copy-number changes with high-resolution aCGH
      (array comparative genomic hybridization) containing 385 thousand probes (about
      one for each 7 kbp) and expression of phenotypic markers on TMAs (tissue
      microarrays). The data were examined with respect to clinical parameters
      including TNM staging, histologic grade, S phase, and ploidy. RESULTS: Tumors
      from BRCA2 carriers of luminal and basal/triple-negative phenotypes (TNPs) differ
      with respect to patterns of DNA copy-number changes. The basal/TNP subtype was
      characterized by lack of pRb (RB1) coupled with high/intense expression of p16
      (CDKN2A) gene products. We found increased proportions of Ki-67-positive cells to
      be significantly associated with loss of the wild-type (wt) BRCA2 allele in
      luminal types, whereas BRCA2wt loss was less frequent in BRCA2 tumors displaying
      basal/TNP phenotypes. Furthermore, we show that deletions at 13q13.1, involving
      the BRCA2wt allele, represents a part of a larger network of co-occurring genetic
      changes, including deletions at 6q22.32-q22.33, 11q14.2-q24.1, and gains at
      17q24.1. Importantly, copy-number changes at these BRCA2-linked networking
      regions coincide with those associated with advanced progression, involving the
      capacity to metastasize to the nodes or more-distant sites at diagnosis.
      CONCLUSIONS: The results presented here demonstrate divergent paths of tumor
      evolution in BRCA2 carriers and that deletion of the wild-type BRCA2 allele,
      together with co-occurring changes at 6 q, 11 q, and 17 q, are important events
      in progression toward advanced disease.

PMID- 21958416
TI  - Even low level of physical activity is associated with reduced mortality among
      people with metabolic syndrome, a population based study (the HUNT 2 study,
      Norway).
AB  - BACKGROUND: Low levels of physical activity may increase the risk of developing
      metabolic syndrome, a cluster of metabolic factors that are associated with the
      risk of premature death. It has been suggested that physical activity may reduce
      the impact of factors associated with metabolic syndrome, but it is not known
      whether physical activity may reduce mortality in people with metabolic syndrome.
      METHODS: In a prospective study of 50,339 people, 13,449 had metabolic syndrome
      at baseline and were followed up for ten years to assess cause-specific
      mortality. The population was divided into two age groups: those younger than 65
      years of age and those older than age 65. Information on their physical activity
      levels was collected at baseline. RESULTS: Metabolic syndrome was associated with
      higher mortality from all causes (hazard ratio (HR) 1.35, 95% confidence interval
      (95% CI) 1.20 to 1.52) and from cardiovascular causes (HR 1.78, 95% CI 1.39 to
      2.29) in people younger than 65 years old than among other populations. In older
      people, there was no overall association of metabolic syndrome with mortality.
      People with metabolic syndrome who reported high levels of physical activity at
      baseline were at a reduced risk of death from all causes compared to those who
      reported no physical activity, both in the younger age group (HR 0.52, 95% CI
      0.37 to 0.73) and in the older age group (HR 0.59, 95% CI 0.47 to 0.74).
      CONCLUSION: Among people with metabolic syndrome, physical activity was
      associated with reduced mortality from all causes and from cardiovascular causes.
      Compared to inactivity, even low levels of physical activity were associated with
      reduced mortality.

PMID- 21958429
TI  - The Sasang constitutional types can act as a risk factor for hypertension.
AB  - It has been suggested that an approach to hypertension based on the
      constitutional make-up of an individual may be effective. We conducted a
      retrospective chart review to explore the association of Sasang constitution with
      hypertension. The results show that the prevalence of hypertension was highest in
      the Taeeum (TE) constitutional type, and that the TE constitutional type can act
      as an independent risk factor for hypertension (OR in TE group = 1.37 (CI 1.06
      1.78) (vs. non-TE group)). This indicates that the Sasang constitutional type
      could explain the variability in individual susceptibilities to hypertension,
      suggesting a novel constitution-based approach to hypertension.

PMID- 21958417
TI  - CD8 T cells and E-cadherin in host responses against oropharyngeal candidiasis.
AB  - BACKGROUND: Oropharyngeal candidiasis (OPC) is the most common oral infection in
      HIV(+) persons. Previous studies suggest a role for CD8(+) T cells against OPC
      when CD4(+) T cells are lost, but enhanced susceptibility to infection occurs
      when CD8(+) T-cell migration is inhibited by reduced tissue E-cadherin.
      OBJECTIVE:   To conduct a longitudinal study of tissue CD8(+) T-cells and E
      cadherin expression before, during, and after the episodes of OPC. METHODS: Oral
      fungal burden was monitored and tissue was evaluated for CD8(+) T cells and E
      cadherin over a 1-year period in HIV(+) persons with a history of, or an acute
      episode of, OPC. RESULTS: While longitudinal analyses precluded formal
      interpretations, point prevalence analyses of the data set revealed that when
      patients experiencing OPC were successfully treated, tissue E-cadherin expression
      was similar to that in patients who had not experienced OPC, and higher numbers
      of CD8(+) T cells were distributed throughout OPC(-) tissue under normal
      expression of E-cadherin. CONCLUSION: These results suggest that (1) reduction in
      tissue E-cadherin expression in patients with OPC(+) is not permanent, and (2)
      high numbers of CD8(+) T cells can be distributed throughout OPC(-) tissue under
      normal E-cadherin expression. Together, these results extend our previous studies
      and continue to support a role for CD8(+) T cells in host defense against OPC.

PMID- 21958418
TI  - Geriatric rehabilitation of lower limb amputees: a multicenter study.
AB  - PURPOSE: The aim of this study was to determine factors independently associated
      with successful rehabilitation of patients with lower limb amputation in skilled
      nursing facilities (SNFs). METHODS: All patients admitted to one of the 11
      participating SNFs were eligible. Multidisciplinary teams collected the data.
      Successful rehabilitation was defined as discharge to an independent living
      situation within 1 year after admission. Functional status at discharge, as
      measured with the Barthel index (BI), was a secondary outcome. Multivariate
      regression analyses were used to assess the independent contribution of each
      determinant to the two outcome measures. RESULTS: Of 55 eligible patients, 48
      were included. Mean age was 75 years. Sixty-five percent rehabilitated
      successfully. Multivariate analyses showed that presence of diabetes mellitus
      (DM) (OR 23.87, CI 2.26-252.47) and premorbid BI (OR 1.37, CI 1.10-1.70) were the
      most important determinants of successful rehabilitation, whereas 78% of the
      variance of discharge BI was explained by premorbid BI, BI on admission, and 1
      leg balance. CONCLUSION: The presence of DM and high premorbid BI were associated
      with discharge to an independent living situation within 1 year after admission.
      Premorbid BI, admission BI, and 1-leg balance were independently associated to
      discharge BI.

PMID- 21958430
TI  - Arm span as a proxy measure for height and estimation of nutritional status: a
      study among Dhimals of Darjeeling in West Bengal India.
AB  - OBJECTIVES: This study aimed to understand the interrelationship between height
      and arm span and also to estimate nutritional status from arm span. METHODS: In
      an anthropometric survey conducted among the Dhimals (227 males and 223 females,
      total = 450) of Naxalbari in West Bengal, India, measurements were recorded in
      age groups ranging between 10-59 years. RESULTS: Males were taller and had longer
      arm spans than females. The height-arm span ratio was 0.98-0.99, indicating
      height to be slightly less than arm span in both sexes. High correlation between
      these two dimensions was also observed. Regression equations provided a good
      model for estimating height from arm span (predictor). In all age groups of both
      sexes, values of standardized coefficient beta exhibited high significance (p (
      0.001). Residuals showed no pattern and were random. No significant difference
      between height-based body mass index or BMI (body weight/height(2)) and estimated
      arm span-based BMI (body weight/arm span(2)) was observed in any age group.
      CONCLUSION: Arm span was found to be an effective surrogate measure for BMI.

PMID- 21958428
TI  - Recommendations for and compliance with social restrictions during implementation
      of school closures in the early phase of the influenza A (H1N1) 2009 outbreak in
      Melbourne, Australia.
AB  - BACKGROUND: Localized reactive school and classroom closures were implemented as
      part of a suite of pandemic containment measures during the initial response to
      influenza A (H1N1) 2009 in Melbourne, Australia. Infected individuals, and those
      who had been in close contact with a case, were asked to stay in voluntary home
      quarantine and refrain from contact with visitors for seven days from the date of
      symptom onset or exposure to an infected person. Oseltamivir (Tamiflu) was
      available for treatment or prophylaxis. METHODS: We surveyed affected families
      through schools involved in the closures. Analyses of responses were descriptive.
      We characterized recommendations made to case and contact households and
      quantified adherence to guidelines and antiviral therapy. RESULTS: Of the 314
      respondent households, 51 contained a confirmed case. The prescribed quarantine
      period ranged from 1-14 days, reflecting logistic difficulties in reactive
      implementation relative to the stated guidelines. Household-level compliance with
      the requirement to stay at home was high (84.5%, 95% CI 79.3,88.5) and contact
      with children outside the immediate family infrequent. CONCLUSIONS: Levels of
      compliance with recommendations in our sample were high compared with other
      studies, likely due to heightened public awareness of a newly introduced virus of
      uncertain severity. The variability of reported recommendations highlighted the
      difficulties inherent in implementing a targeted reactive strategy, such as that
      employed in Melbourne, on a large scale during a public health emergency. This
      study emphasizes the need to understand how public health measures are
      implemented when seeking to evaluate their effectiveness.

PMID- 21958431
TI  - Total synthesis of (+/-)-dragmacidin E.
AB  - The bis indole sponge alkaloid dragmacidin E was synthesized in racemic form over
      25 steps starting from 7-benzhydroxyindole. Key steps include (a) a Witkop
      cyclization to facilitate construction of the indole-spanning seven-membered ring
      and (b) a cyclodehydrative pyrazinone synthesis that unites the two indole
      containing sectors.

PMID- 21958423
TI  - Cyclic di-nucleotides: new era for small molecules as adjuvants.
AB  - The implementation of vaccination as an empiric strategy to protect against
      infectious diseases was introduced even before the advent of hygiene and
      antimicrobials in the medical practice. Nevertheless, it was not until a few
      decades ago that we really started understanding the underlying mechanisms of
      protection triggered by vaccination. Vaccines were initially based on attenuated
      or inactivated organisms. Subunit vaccines were then introduced as more refined
      formulations, exhibiting improved safety profiles. However, purified antigens
      tend to be poorly immunogenic and often require the use of adjuvants to achieve
      adequate stimulation of the immune system. Vaccination strategies, such as
      mucosal administration, also require potent adjuvants to improve performance. In
      the 1990s, immunologists found that pathogens could be sensed as 'danger signals'
      by receptors recognizing conserved motifs. Although our knowledge is still
      limited, tremendous advances were made in the understanding of host defence
      mechanisms regulated by these evolutionary conserved receptors, and the molecular
      structures which are recognized by them. This opened a new era in adjuvant
      development. Some of the latest players arrived to this field are the cyclic di
      nucleotides, which are ubiquitous prokaryotic intracellular signalling molecules.
      This review is focused on their potential for the development of vaccines and
      immunotherapies.

PMID- 21958436
TI  - Large-area high-quality plasmonic oligomers fabricated by angle-controlled
      colloidal nanolithography.
AB  - We introduce angle-controlled colloidal nanolithography as a fast and low-cost
      fabrication technique for large-area periodic plasmonic oligomers with complex
      shapes and tunable geometry parameters. We investigate the optical properties and
      find highly modulated plasmon modes in oligomers with triangular building blocks.
      Fundamental modes, higher-order modes, as well as Fano resonances due to coupling
      between bright and dark modes within the same complex structure are present,
      depending on polarization and structure geometry. Our process is well-suited for
      mass fabrication of novel large-area plasmonic sensing devices and nanoantennas.

PMID- 21958435
TI  - Staging of laryngeal carcinoma: comparison of high-frequency sonography and
      contrast-enhanced computed tomography.
AB  - AIM: To evaluate the accuracy of high-frequency sonography on pretherapeutic T
      staging in patients with laryngeal carcinoma. MATERIALS AND METHODS: Thirty-six
      consecutive patients with laryngeal carcinoma undergoing surgical resection were
      included in this study. All patients underwent ultrasonographic examination and
      contrast-enhanced computed tomography before surgery. These imaging
      interpretations were evaluated independently and then compared with the reference
      of postoperative pathological examination. McNemar's test was used for comparing
      the data obtained separately from ultrasonography and computed tomography.
      RESULTS: There was one T2 stage tumour of an aryepiglottic fold undetected by
      sonography. Sonography failed to stage five tumours correctly; the T-staging
      accuracy was 83.3%. Contrast-enhanced computed tomography failed to stage four
      patients correctly; the T-staging accuracy was 88.8%. There was no difference
      between the pretherapeutic staging accuracy of ultrasonography and contrast
      enhanced computed tomography (p=0.735). CONCLUSION: Ultrasonography has a
      reliable pretherapeutic staging accuracy of laryngeal carcinoma. It can be a non
      invasive complementary technique for pretherapeutic staging of laryngeal
      carcinoma.

PMID- 21958432
TI  - Are self-reported symptoms of executive dysfunction associated with objective
      executive function performance following mild to moderate traumatic brain injury?
AB  - BACKGROUND AND OBJECTIVE: We examined the relationship between self-reported pre-
      and post-injury changes in executive dysfunction, apathy, disinhibition, and
      depression, and performance on neuropsychological tests of executive function,
      attention/processing speed, and memory in relation to mood levels and effort test
      performance in individuals in the early stages of recovery from mild to moderate
      traumatic brain injury (TBI). METHOD: Participants were 71 noncombat military
      personnel who were in a semiacute stage of recovery (<3 months post injury) from
      mild to moderate TBI. Pre- and post-TBI behaviors were assessed with the Frontal
      Systems Behavior Scale (FrSBe; Grace & Malloy, 2001 ) and correlated with levels
      of depressive symptoms, effort test performance, and performance on objective
      measures of attention, executive function, and memory. RESULTS: Self-reported
      symptoms of executive dysfunction generally failed to predict performance on
      objective measures of executive function and memory, although they predicted
      poorer performance on measures of attention/processing speed. Instead, higher
      levels of depressive symptomatology best predicted poorer performance on measures
      of executive function and memory. However, the relationship between memory
      performance and TBI symptoms was no longer significant when effort performance
      was controlled. CONCLUSIONS: Our findings suggest that, among individuals in
      early recovery from mild to moderate TBI, self-reported depressive symptoms,
      rather than patients' cognitive complaints, are associated with objective
      executive function. However, self-reported cognitive complaints may be associated
      with objectively measured inattention and slow processing speed.

PMID- 21958434
TI  - Up-regulation of dorsal root ganglia BDNF and trkB receptor in inflammatory pain:
      an in vivo and in vitro study.
AB  - BACKGROUND: During inflammation, immune cells accumulate in damaged areas and
      release pro-inflammatory cytokines and neurotrophins. Brain-derived neurotrophic
      factor (BDNF) plays a neuromodulatory role in spinal cord dorsal horn via the
      post-synaptic tyrosine protein kinase B (trkB) receptor to facilitate pain
      transmission. However, the precise role of BDNF and trkB receptor in the primary
      sensory neurons of dorsal root ganglia (DRG) during inflammation remains to be
      clarified. The aim of this study was to investigate whether and how BDNF-trkB
      signaling in the DRG is involved in the process of inflammatory pain. METHODS: We
      used complete Freund's adjuvant- (CFA-) induced and tumor necrosis factor-alpha-
      (TNF-alpha-) induced inflammation in rat hindpaw as animal models of inflammatory
      pain. Quantification of protein and/or mRNA levels of pain mediators was
      performed in separate lumbar L3-L5 DRGs. The cellular mechanism of TNF-alpha
      induced BDNF and/or trkB receptor expression was examined in primary DRG cultures
      collected from pooled L1-L6 DRGs. Calcitonin gene-related peptide (CGRP), BDNF
      and substance P release were also evaluated by enzyme immunoassay. RESULTS: CFA
      injection into rat hindpaw resulted in mechanical hyperalgesia and significant
      increases in levels of TNF-alpha in the inflamed tissues, along with enhancement
      of BDNF and trkB receptor as well as the pain mediators CGRP and transient
      receptor potential vanilloid receptor subtype 1 (TRPV1) in DRG. Direct injection
      of TNF-alpha into rat hindpaw resulted in similar effects with retrograde
      transport of TNF-alpha along the saphenous nerve to DRG during CFA-induced
      inflammation. Primary DRG cultures chronically treated with TNF-alpha showed
      significant enhancement of mRNA and protein levels of BDNF and trkB receptor,
      BDNF release and trkB-induced phospho-ERK1/2 signal. Moreover, CGRP and substance
      P release were enhanced in DRG cultures after chronic TNF-alpha treatment or
      acute BDNF stimulation. In addition, we found that BDNF up-regulated trkB
      expression in DRG cultures. CONCLUSIONS: Based on our current experimental
      results, we conclude that inflammation and TNF-alpha up-regulate the BDNF-trkB
      system in DRG. This phenomenon suggests that up-regulation of BDNF in DRG may, in
      addition to its post-synaptic effect in spinal dorsal horn, act as an autocrine
      and/or paracrine signal to activate the pre-synaptic trkB receptor and regulate
      synaptic excitability in pain transmission, thereby contributing to the
      development of hyperalgesia.

PMID- 21958439
TI  - Gastrointestinal involvement revealing Henoch Schonlein purpura in adults: Report
      of three cases and review of the literature.
AB  - The diagnosis of Henoch-Schonlein purpura (HSP) is difficult, especially when
      abdominal symptoms precede cutaneous lesions.  We report three cases of adult HSP
      revealed by gastrointestinal (GI) involvement.

PMID- 21958438
TI  - Safety and efficacy of sorafenib in hepatocellular carcinoma: the impact of the
      Child-Pugh score.
AB  - BACKGROUND: Sorafenib increases median survival and time to radiological
      progression in patients with advanced hepatocellular carcinoma, but its benefit
      for Child-Pugh B patients remains uncertain. AIM: To evaluate the safety and
      efficacy of sorafenib in real-life clinical practice conditions and to assess the
      influence of Child-Pugh class B on safety and efficacy. METHODS: All patients
      treated with sorafenib for advanced hepatocellular carcinoma in our institution
      were included prospectively. Adverse events, overall survival and time to
      progression were recorded. A case control study was performed to compare outcome
      of patients with comparable stages of hepatocellular carcinoma, but a different
      Child-Pugh class. RESULTS: From March 2007 to May 2009, 120 patients were
      included. Overall survival was 11.1 months, Child-Pugh A patients (n=100) had
      significantly higher median survival than Child-Pugh B patients (n=20) (13 vs.
      4.5 months, P=0.0008). In multivariate analysis, Child-Pugh class B, alpha
      fetoprotein level and total size of lesions were independent predictive factors
      of death. Patients with radiological progression in the first 3 months had
      shorter median survival (5.4 vs. 17.4 months). In a case control study, time to
      symptomatic progression (2.5 vs. 3.6 months), frequency of adverse events and
      discontinuation of sorafenib were not correlated with Child-Pugh class.
      CONCLUSIONS: Patients with advanced hepatocellular carcinoma treated with
      sorafenib had a median survival of 11 months. Sorafenib therapy must be
      considered with caution in Child-Pugh B patients due to their poor survival.
      Radiological assessment of tumour progression at an early stage may be
      advantageous when tailoring sorafenib therapy.

PMID- 21958437
TI  - Neospora caninum and Toxoplasma gondii in brain tissue of feral rodents and
      insectivores caught on farms in the Netherlands.
AB  - We investigated the presence of both Neospora caninum and Toxoplasma gondii in
      250 brain tissue samples from 9 species of feral rodents and insectivores caught
      on 10 organic farms in the Netherlands in 2004. Collected samples were conserved
      in 4% paraformaldehyde solution and analysed by real-time PCR. For N. caninum, 31
      samples originating from 6 species tested positive (12.4%): common shrews
      (33.3%), wood mice (17.6%), harvest mice (16.7%), house mice (15.4%), white
      toothed shrews (10.8%) and common voles (4.2%). For T. gondii, the overall
      contamination level was 4%, and only three species were found to be positive:
      house mice (9.0%), common voles (4.2%) and white-toothed shrews (2.0%). Most N.
      caninum infected samples (27/31; 87%) were found on farms where dogs were
      present. Due to the observation that rodents and insectivores can contract both
      parasites, they might function as indicator species for the parasitic load on
      farms.

PMID- 21958441
TI  - Alcohols solubilization in a nonionic fluorinated surfactant based system:
      effects on the characteristics of mesoporous silica.
AB  - In this study, we have used hydrogenated alcohols with different chain lengths
      and one fluorinated alcohol as additives to determine their effect on the
      characteristics of mesoporous materials prepared from fluorinated micelles.

PMID- 21958440
TI  - Vascular endothelial growth factor plasma levels before and after treatment of
      neovascular age-related macular degeneration with bevacizumab or ranibizumab.
AB  - PURPOSE: To evaluate the changes of vascular endothelial growth factor (VEGF)
      plasma levels after intravitreal injections of ranibizumab or bevacizumab in
      patients with exudative age-related macular degeneration (AMD). METHODS: Forty
      three patients with exudative AMD and 19 age- and sex-matched control patients
      without chorioretinal diseases were studied. Nineteen patients were treated with
      intravitreal ranibizumab 0.5 mg, 24 with intravitreal bevacizumab 1.25 mg. Blood
      samples were collected just before the first injection, and 28 days after three
      initial consecutive injections performed in 4-weekly intervals (loading dose).
      Concentration of VEGF in the plasma was measured by ELISA. RESULTS: At baseline,
      the median VEGF concentrations in controls were 180.97 pg/ml, in the bevacizumab
      group 189.72 pg/ml and in the ranibizumab group 191.36 pg/ml. VEGF plasma
      concentrations in patients with wet AMD were comparable to controls (p = 0.225).
      Twenty-eight days after the third injection, a significant reduction of 42% in
      the median VEGF plasma levels was found in bevacizumab-treated patients (109.97
      pg/ml; p = 0.0002) but not in ranibizumab-treated patients (189.97 pg/ml; p =
      0.198) where a reduction of 0.7% in the median value was found. CONCLUSIONS:
      Intravitreal bevacizumab significantly reduced VEGF plasma levels until 28 days
      after intravitreal injection in patients with exudative AMD. Ranibizumab did not
      achieve a significant plasma VEGF reduction at the same time-point. These
      findings alert to the potential systemic safety differences between the two drugs
      after intravitreal administration.

PMID- 21958445
TI  - Safe use of electroconvulsive therapy in a highly suicidal survivor of carbon
      monoxide poisoning.
AB  - It has been reported that electroconvulsive therapy (ECT) may increase the
      likelihood of delayed neuropsychiatric sequelae (DNS) after carbon monoxide (CO)
      poisoning. We present a suicidal patient of CO intoxication, who received ECT
      safely and effectively 5 weeks after CO exposure and review the previously
      reported ECT-related DNS cases and the recent studies about the predictors of
      DNS. We propose that ECT can be safely implemented in carefully selected patients
      without known risk factors for DNS after an extended observation period from CO
      exposure.

PMID- 21958444
TI  - Psychiatric morbidity in mothers of children attending primary care facility in
      Ilorin, Nigeria: drawing attention to those affected concurrently with their
      children.
AB  - OBJECTIVE: To determine the prevalence of psychiatric morbidity among mothers of
      children attending a primary care clinic in University of Ilorin Teaching
      Hospital as precursor to developing an intervention programme. METHOD: WThree
      hundred fifty mothers of children aged 7-14 years were screened with the 12-item
      General Health Questionnaire for psychiatric morbidity. As part of the larger
      study, their children were screened for psychiatric disorders with the parents'
      version of the Child Behaviour Questionnaire, and a subsample of 157 mother/child
      dyad had second-stage interview with the children's version of the Schedule for
      Affective Disorders and Schizophrenia to determine psychiatric morbidity in these
      children. RESULTS: Twenty-eight out of 350 mothers (8%) had probable psychiatric
      morbidity. Mothers with psychiatric morbidity were significantly more likely to
      have children with Diagnostic and Statistical Manual of Mental Disorder, Fourth
      Edition psychiatric diagnosis (8 of 28, P=0.011), experience parenting
      difficulties with some of their children (13 of 28, P=0.000) and have poor
      husband support for the care of their children. CONCLUSION: The presence of
      psychiatric morbidity in mothers may require that other members of the family
      especially the children be screened for psychiatric disorders particularly when
      there are parenting difficulties and poor spousal support; in this way primary
      prevention or control can effectively be carried out.

PMID- 21958443
TI  - Dextran and hydroxyethyl starch do not interfere with fibrinogen measurement if
      Clauss method with mechanical clot detection is used.

PMID- 21958446
TI  - Posttraumatic stress syndromes and health-related quality of life following
      myocardial infarction: 8-year follow-up.
AB  - OBJECTIVES: This study examines the implications of acute stress disorder (ASD),
      following myocardial infraction (MI), in predicting subsequent posttraumatic
      stress disorder (PTSD) and impaired quality of life (QoL) 8 years post-MI.
      METHODS: MI patients, who were assessed within a week of the MI (Time 1; n=173),
      were followed up 7 months (Time 2; n=116) and 8 years (Time 3; n=90) post-MI. ASD
      was assessed at Time 1 and PTSD at Time 2 and Time 3. Health-related QoL was
      assessed at Time 3. RESULTS: Unconditional latent class growth models revealed
      two distinct subpopulations: the recovered/resilient group (94%) demonstrated a
      decrease from 12.4% of ASD at Time 1 to 6.1% of PTSD at Time 3. Rates of
      posttraumatic stress syndromes in the chronic group (6%) were 85.3% at Time 1 and
      75.7% at Time 3. The two groups differed in pre-MI life events, length of
      hospitalization, likelihood to have anterior MI, and perceived threat of death.
      The chronic group reported lower levels of QoL at Time 3. CONCLUSION: Although
      most ASD patients demonstrate a trend of recovery, ASD in the immediate aftermath
      of MI remains a marker of long term adjustment difficulties.

PMID- 21958442
TI  - The role of glycerol and phosphatidylcholine in solubilizing and enhancing
      insulin stability in reverse hexagonal mesophases.
AB  - The potential of reverse hexagonal mesophases based on monoolein (GMO) and
      glycerol (as cosolvent) to facilitate the solubilization of proteins, such as
      insulin was explored. H(II) mesophases composed of GMO/decane/water were compared
      to GMO/decane/glycerol/water and GMO/phosphatidylcholine
      (PC)/decane/glycerol/water systems. The stability of insulin was tested, applying
      external physical modifications such as low pH and heat treatment (up to 70
      degrees C), in which insulin is known to form ordered amyloid-like aggregates
      (that are associated with several neurodegenerative diseases) with a
      characteristic cross beta-pleated sheet structure. The impact of insulin
      confinement within these carriers on its stability, unfolding, and aggregation
      pathways was studied by combining SAXS, FTIR, and AFM techniques. These
      techniques provided a better insight into the molecular level of the "component
      interplay" in solubilizing and stabilizing insulin and its conformational
      modifications that dictate its final aggregate morphology. PC enlarged the water
      channels while glycerol shrank them, yet both facilitated insulin solubilization
      within the channels. The presence of glycerol within the mesophase water channels
      led to the formation of stronger hydrogen bonds with the hosting medium that
      enhanced the thermal stability of the protein and remarkably affected the
      unfolding process even after heat treatment (at 70 degrees C for 60 min).

PMID- 21958451
TI  - Quantum chemical study of carbohydrate-phospholipid interactions.
AB  - Carbohydrates on host membranes are fundamental to many important biological
      processes. Here, we seek a basic understanding of the nature of the interactions
      between carbohydrates and phospholipids to dissect their roles in molecular
      recognition. A hybrid quantum mechanics/quantum mechanics (QM/QM) scheme with two
      different levels of treatment was used to explore the conformations and
      energetics of carbohydrate-phospholipid complexes. We investigate the
      interactions of two phospholipids (POPC and DOPC) with mannose using density
      functional theory. Carbohydrate-phospholipid interactions are probed with respect
      to competing interactions with water. Our hybrid QM/QM approach demonstrates that
      mannose interactions with phospholipids can result in alterations in charge
      distributions and conformations of phospholipids. The results clearly reveal the
      interplay between conventional and nonconventional hydrogen bonding; moreover,
      nonpolar interactions are shown to be crucial in the recognition and further
      stabilization of carbohydrate-phospholipid complexes. The influence of the acyl
      chain on phospholipid headgroup orientation is clearly evident in our
      investigation. The significance of the conventional OH...O and nonconventional
      CH...O and CH...C interactions in the stabilization of the intermolecular
      complexes is deduced from the molecular electron density topology using Bader's
      atoms-in-molecules theory. Finally, we have compared the QM energies with
      molecular mechanics energies for the same interactions to aid in the refinement
      of the all-atom lipid-carbohydrate force fields.

PMID- 21958448
TI  - Treatment decision-making for advanced non-small cell lung cancer and differences
      among European countries: 1st AIOT-ETOP meeting.
AB  - INTRODUCTION: The Italian Association of Thoracic Oncology (AIOT) and the
      European Thoracic Oncology Platform (ETOP) realized the first conjunct
      educational meeting, open to European oncologists involved in the treatment of
      thoracic malignancies, entitled "Advanced non-small cell lung cancer: new
      perspectives in first-line setting". METHODS: The educational meeting included 8
      interactive talks, held by European key opinion leaders, and 5 related clinical
      cases in which the attendees, divided in working tables based on their country
      origin, were involved for interactive discussion. The aim of this course was to
      elucidate the differences or similarities among the European countries in the
      first-line treatment of patients affected by advanced non-small cell lung cancer
      (NSCLC). RESULTS: Twenty-two attendees of the following countries participated:
      Austria, France, Italy, Spain, Swiss, and UK. As expected, some discrepancies
      between the groups were identified concerning the approach to the diagnostic
      phase, the choice of first-line regimen, the duration of treatment and the use of
      maintenance therapy. These discrepancies were mainly due to familiarity with
      specific therapies and lack of access to certain therapies due to local
      regulatory issues. CONCLUSION: The European Medicine Agency grants marketing of
      drugs in all Europe, regulatory agency of each country can register the drug, but
      can also deny public reimbursement thus restricting the options of the
      oncologist. The European Oncology Associations should join to their effort to
      achieve a uniform access to the cancer therapy for all patients in Europe.

PMID- 21958433
TI  - Damage-associated molecular patterns (DAMPs) in preterm labor with intact
      membranes and preterm PROM: a study of the alarmin HMGB1.
AB  - OBJECTIVE: Preterm parturition is a syndrome caused by multiple etiologies.
      Although intra-amniotic infection is causally linked with intrauterine
      inflammation and the onset of preterm labor, other patients have preterm labor in
      the absence of demonstrable infection. It is now clear that inflammation may be
      elicited by activation of the Damage-Associated Molecular Patterns (DAMPs), which
      include pathogen-associated molecular patterns (PAMPs) as well as "alarmins"
      (endogenous molecules that signal tissue and cellular damage). A prototypic
      alarmin is high-mobility group box 1 (HMGB1) protein, capable of inducing
      inflammation and tissue repair when it reaches the extracellular environment.
      HMGB1 is a late mediator of sepsis, and blockade of HMGB1 activity reduces
      mortality in an animal model of endotoxemia, even if administered late during the
      course of the disorder. The objectives of this study were to: (1) determine
      whether intra-amniotic infection/inflammation (IAI) is associated with changes in
      amniotic fluid concentrations of HMGB1; and (2) localize immunoreactivity of
      HMGB1 in the fetal membranes and umbilical cord of patients with
      chorioamnionitis. METHODS: Amniotic fluid samples were collected from the
      following groups: (1) preterm labor with intact membranes (PTL) with (n=42) and
      without IAI (n=84); and (2) preterm prelabor rupture of membranes (PROM) with
      (n=38) and without IAI (n=35). IAI was defined as either a positive amniotic
      fluid culture or amniotic fluid concentration of interleukin-6 (IL-6) >=
      2.6ng/mL. HMGB1 concentrations in amniotic fluid were determined by ELISA.
      Immunofluorescence staining for HMGB1 was performed in the fetal membranes and
      umbilical cord of pregnancies with acute chorioamnionitis. RESULTS: (1) Amniotic
      fluid HMGB1 concentrations were higher in patients with IAI than in those without
      IAI in both the PTL and preterm PROM groups (PTL IAI: median 3.1 ng/mL vs.
      without IAI; median 0.98 ng/mL; p <0.001; and preterm PROM with IAI median 7.3
      ng/mL vs. without IAI median 2.6 ng/mL; p=0.002); (2) patients with preterm PROM
      without IAI had a higher median amniotic fluid HMGB1 concentration than those
      with PTL and intact membranes without IAI (p <0.001); and (3) HMGB1 was
      immunolocalized to amnion epithelial cells and stromal cells in the Wharton's
      jelly (prominent in the nuclei and cytoplasm). Myofibroblasts and macrophages of
      the chorioamniotic connective tissue layer and infiltrating neutrophils showed
      diffuse cytoplasmic HMGB1 immunoreactivity. CONCLUSIONS: (1) intra-amniotic
      infection/inflammation is associated with elevated amniotic fluid HMGB1
      concentrations regardless of membrane status; (2) preterm PROM was associated
      with a higher amniotic fluid HMGB1 concentration than PTL with intact membranes,
      suggesting that rupture of membranes is associated with an elevation of alarmins;
      (3) immunoreactive HMGB1 was localized to amnion epithelial cells, Wharton's
      jelly and cells involved in the innate immune response; and (4) we propose that
      HMGB1 released from stress or injured cells into amniotic fluid may be
      responsible, in part, for intra-amniotic inflammation due to non-microbial
      insults.

PMID- 21958449
TI  - Statin use and the risk of female lung cancer: a population-based case-control
      study.
AB  - The aim of this study was to investigate whether the use of statins was
      associated with lung cancer risk. We conducted a population-based case-control
      study in Taiwan. Data were retrospectively collected from the Taiwan National
      health Insurance Research Database. Cases consisted of all female patients who
      were aged 50 years and older and had a first-time diagnosis of lung cancer for
      the period between 2005 and 2008. We identified four control patients per case
      patient. The controls were matched to cases by age, sex, and index date. Adjusted
      odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by using
      multiple logistic regression. We examined 297 female lung cancer cases and 1188
      controls. The unadjusted odds ratios (ORs) for any statin prescription were 0.78
      (95% confidence interval=0.57-1.07) and the adjusted OR was 0.82 (95% CI=0.58
      1.15). Compared with no use of statins, the adjusted ORs were 0.83 (95% CI=0.54
      1.28) for the group having been prescribed statins with cumulative defined daily
      dose (DDDs) below 92.41 and 0.79 (95% CI=0.50-1.25) for the group with cumulative
      statin use of 92.41 DDDs or more. The present data do not provide support for a
      beneficial association between statin use and female lung cancer risk.

PMID- 21958450
TI  - A dual-catalysis approach to the asymmetric Steglich rearrangement and catalytic
      enantioselective addition of O-acylated azlactones to isoquinolines.
AB  - A dual-catalysis approach, namely the combination of an achiral nucleophilic
      catalyst and a chiral anion-binding catalyst, was applied to the Steglich
      rearrangement to provide alpha,alpha-disubstituted amino acid derivatives in a
      highly enantioselective fashion. Replacement of the nucleophilic co-catalyst for
      isoquinoline resulted in a divergent reaction pathway and an unprecedented
      transformation of O-acylated azlactones. This strategy provided highly
      substituted alpha,beta-diamino acid derivatives with excellent levels of
      stereocontrol.

PMID- 21958453
TI  - Risk factors associated with delayed diagnosis of acute pulmonary embolism.
AB  - BACKGROUND: Prompt diagnosis and treatment of acute pulmonary embolism (PE) is
      essential to reduce mortality. Risk factors for PE are well known, but factors
      associated with delayed diagnosis are less clear. OBJECTIVE: Our objective was to
      identify clinical factors associated with delayed diagnosis of patients with
      acute PE presenting to a tertiary-care emergency department (ED). METHODS: We
      studied 400 consecutive adults who presented to our ED with acute, symptomatic
      PE. All patients were diagnosed by computed tomography (CT) angiography. Early
      diagnosis was defined as CT diagnosis<12h from ED arrival, and delayed diagnosis
      as CT diagnosis>12h. Univariate and multiple logistic regression models were used
      to identify factors associated with delayed diagnosis. Odds ratios with 95%
      confidence intervals are reported. RESULTS: The median time from arrival to
      diagnosis was 2.4h (interquartile range 1.4-7.6), and 73 (18.3%) patients had
      delayed diagnosis. Patients aged>65 years and those with coronary artery disease
      or congestive heart failure had longer times from ED arrival to CT diagnosis,
      whereas patients with recent immobility had shorter times. Patients diagnosed>12h
      were older and had higher rates of morbid obesity and coronary artery disease,
      whereas patients diagnosed<12h had higher rates of tachycardia. In multiple
      regression modeling, tachycardia and recent immobility remained associated with
      early diagnosis, whereas morbid obesity remained associated with delayed
      diagnosis. CONCLUSIONS: Older patients with cardiovascular comorbidities had
      longer times from ED arrival to CT diagnosis. Our data suggest that these
      patients represent more of a diagnostic challenge than those presenting with
      traditional risk factors for PE, such as tachycardia and recent immobilization.
      Physicians should consider these factors to diagnosis acute PE promptly in the
      ED.

PMID- 21958454
TI  - Facial ischemia after hyaluronic acid injection.

PMID- 21958447
TI  - Adolescent and parent experiences with a primary care/Internet-based depression
      prevention intervention (CATCH-IT).
AB  - This article describes a mixed-methods approach to understand the experience of
      adolescents involved in the Internet-based intervention for depression, Competent
      Adulthood Transition with Cognitive Behavioral Humanistic and Interpersonal
      Training (CATCH-IT), as well as the experiences of their parents while they were
      involved. Qualitative analysis was done with grounded theory-based categorization
      of interview comments and typed program responses (adolescents only) into themes.
      Quantitative analysis was done with self-report surveys. The article describes
      the nine themes reflecting the adolescent experience and the three themes
      reflecting the parent experience. The article also describes the results of the
      quantitative surveys of helpfulness and attitudes change, which were favorable of
      the Internet-based intervention. Separate models explaining the psychological
      transformation of the adolescents and the experience of the parents are proposed.
      The positive experience of the adolescents and parents involved in CATCH-IT is
      discussed in the context of growing interest in how best to utilize Internet
      based interventions for mental illness, and suggestions are made for future
      investigation.

PMID- 21958452
TI  - Derivation and validation of a short emergency department screening tool for
      perpetrators of intimate partner violence: the PErpetrator RaPid Scale (PERPS).
AB  - BACKGROUND: There is no short screening tool for perpetrators of intimate partner
      violence (IPV), although one is needed. OBJECTIVE: To retrospectively derive and
      prospectively validate a brief screening tool for perpetrators of IPV: the
      PErpetration RaPid Scale (PERPS). METHODS: In the derivation phase of the study,
      we developed the PERPS based on historical data. The PERPS consists of three
      Yes/No questions about physical abuse of a partner. In the validation phase, we
      prospectively screened subjects during randomized 4-h shifts in a busy emergency
      department (ED). Subjects were asked to complete the newly derived three-question
      PERPS as well as the Physical Abuse of Partner Scale (PAPS), a 25-question Likert
      scale that is the gold standard for detection of physical abuse of a partner. The
      main outcome measures were sensitivity, specificity, predictive values, accuracy,
      and Cronbach alpha of the PERPS for internal consistency. RESULTS: The PERP Scale
      derivation was based on a 207-subject historical database, and resulted in a
      three-question PERPS. Validation was completed on a new set of 214 patients
      presenting to the ED during 52 randomized 4-h shifts. The prevalence of IPV
      perpetration using the PERPS was 47/207 (22.7%; 95% confidence interval [CI] 16
      27). For the PAPS, prevalence was 56/207 (27%; 95% CI 20-32). Compared with the
      PAPS, the sensitivity of the PERPS was 66%, specificity 93%, negative predictive
      value 87%, positive predictive value 78%, with an accuracy of 85%. Cronbach alpha
      of the PERPS was 0.68. Age, gender, and race were not predictive of positive
      results on either scale. CONCLUSION: We successfully derived and validated a
      three-question perpetrator of IPV scale that can be used in a busy ED or office
      setting.

PMID- 21958456
TI  - Successful re-challenge of daptomycin therapy after initial rhabdomyolysis with
      co-administration of simvastatin.

PMID- 21958459
TI  - Ictal haemodynamic changes in a patient affected by "subtle" Epilepsia Partialis
      Continua.
AB  - We report on a 64 year-old woman presenting with Epilepsia Partialis Continua
      (EPC) affecting the left hand since the age of 24 without neurological deficit.
      Structural MRI showed a region of focal cortical dysplasia (FCD) over the right
      central gyrus and lesions in the mesial frontal and occipital cortex secondary to
      perinatal hypoxic injury. Ictal spike haemodynamic mapping using simultaneous EEG
      fMRI revealed significant BOLD signal changes prominent in the region of FCD
      (larger cluster), occipital cortex (global statistical maximum), prefrontal
      cortex and cerebellum. The cluster over FCD was in good agreement with the result
      of EEG source analysis. Our findings provide an interesting illustration of the
      ability of EEG-fMRI to reveal epileptogenic networks confirming the intrinsic
      epileptogenic properties of dysplastic neurons.

PMID- 21958457
TI  - Multiresponsive clay-containing layer-by-layer films.
AB  - We report on polymer/clay layer-by-layer films responsive to multiple stimuli.
      Temperature- and salt-responsive films were constructed using assembly of poly(N
      isopropylacrylamide) (PNIPAM) and montmorillonite clay nanosheets. An additional
      pH response was achieved by depositing and cross-linking hybrid, dual-network
      PNIPAM/clay/PNIPAM/poly(methacrylic acid) (PMAA) multilayers. Both types of films
      remained stable in a wide pH range and were highly swollen. For example,
      PNIPAM/clay films swelled up to ~14.5 times their dry film thickness in low-salt
      solutions at 25  degrees C, as shown by laser scanning confocal microscopy. At
      temperatures higher than PNIPAM's lower critical solution temperature (LCST) of
      32  degrees C, or in 0.3 M Na(2)SO(4) solutions at room temperature, both
      PNIPAM/clay and PNIPAM/clay/PNIPAM/PMAA films reversibly deswelled as a result of
      collapse of PNIPAM chains. Films of both types showed a decrease in permeability
      to fluorescein-tagged dextrans of various molecular weights. Importantly, film
      permeability to dextrans was decreased at temperatures above PNIPAM's LCST, and
      the effect could be reversed by lowering the temperature. Inclusion of PMAA
      within multilayers provided an additional pH response to film swelling and
      permeability. Hybrid PNIPAM/clay/PNIPAM/PMAA films showed drastic deswelling at
      low pH values due to the onset of hydrogen bonding between PNIPAM and PMAA, and
      the diffusion of 70 kDa dextran through multilayers at acidic pH was completely
      blocked. These multiresponse features of clay-containing films make them
      promising candidates for applications in sensing, actuation, and controlled
      delivery.

PMID- 21958455
TI  - Quantifying drug-seeking behavior: a case control study.
AB  - BACKGROUND: Drug-seeking behavior (DSB) is common in the Emergency Department
      (ED), yet the literature describing DSB in the ED consists predominantly of
      anecdotal evidence. STUDY OBJECTIVES: To perform a case-control study examining
      the relative frequency of DSB in suspected drug-seeking patients as compared to
      all ED patients. METHODS: We performed a retrospective chart review of 152 drug
      seeking patients and of age- and gender-matched controls, noting which of the
      following behaviors were exhibited during a 1-year period: reporting a non
      narcotic allergy, requesting addictive medications by name, requesting a
      medication refill, reporting lost or stolen medication, three or more ED visits
      complaining of pain in different body parts, reporting 10 out of 10 pain,
      reporting > 10 out of 10 pain, three or more ED visits within 7 days, reporting
      being out of medication, requesting medications parenterally, and presenting with
      a chief complaint of headache, back pain, or dental pain. RESULTS: The odds
      ratios for each studied behavior being used by drug seeking patients as compared
      to controls were: non-narcotic allergy: 3.4, medication by name: 26.3, medication
      refill: 19.2, lost or stolen medication: 14.1, three or more pain related visits
      in different parts of the body: 29.3, 10 out of 10 pain: 13.9, three visits in 7
      days: 30.8, out of medication: 26.9, headache: 10.9, back pain: 13.6, and dental
      pain: 6.3. Zero patients in the control group complained of greater than 10-out
      of-10 pain or requested medication parenterally, resulting in a calculated odds
      ratio of infinity for these two behaviors. CONCLUSIONS: Requesting parenteral
      medication and reporting greater than ten out of ten pain were most predictive of
      drug-seeking, while reporting a non-narcotic allergy was less predictive of drug
      seeking than other behaviors.

PMID- 21958462
TI  - Bacterial genomes: from regulatory complexity to engineering.

PMID- 21958465
TI  - The gender earnings gap among pharmacists.
AB  - BACKGROUND: A gender earnings gap exists across professions. Compared with men,
      women earn consistently lower income levels. The determinants of wages and
      salaries should be explored to assess whether a gender earnings gap exists in the
      pharmacy profession. OBJECTIVES: The objectives of this study were to (1) compare
      the responses of male and female pharmacists' earnings with human-capital stock,
      workers' preferences, and opinion variables and (2) assess whether the earnings
      determination models for male and female pharmacists yielded similar results in
      estimating the wage-and-salary gap through earnings projections, the influence of
      each explanatory variable, and gender differences in statistical significance.
      METHODS: Data were collected through the use of a 37-question survey mailed to
      registered pharmacists in South Florida, United States. Earnings functions were
      formulated and tested separately for male and female pharmacists using unlogged
      and semilog equation forms. Number of hours worked, human-capital stock, job
      preferences, and opinion variables were hypothesized to explain wage-and-salary
      differentials. RESULTS: The empirical evidence led to 3 major conclusions: (1)
      men's and women's earnings sometimes were influenced by different stimuli, and
      when they responded to the same variables, the effect often was different; (2)
      although the influence of some explanatory variables on earnings differed in the
      unlogged and semilog equations, the earnings projections derived from both
      equation forms for male and female pharmacists were remarkably similar and
      yielded nearly identical male-female earnings ratios; and (3) controlling for
      number of hours worked, human-capital stock, job preferences, and opinion
      variables reduced the initial unadjusted male-female earnings ratios only
      slightly, which pointed toward the presence of gender bias. CONCLUSION: After
      controlling for human-capital stock, job-related characteristics, and opinion
      variables, male pharmacists continued to earn higher income levels than female
      pharmacists.

PMID- 21958460
TI  - Growth of the pancreatic cancer cell line PANC-1 is inhibited by protein
      phosphatase 2A inhibitors through overactivation of the c-Jun N-terminal kinase
      pathway.
AB  - Protein phosphatase 2A (PP2A) is a multimeric serine/threonine phosphatase that
      can dephosphorylate multiple kinases. It is generally considered to be a cancer
      suppressor as its inhibition can induce phosphorylation and activation of
      substrate kinases that mainly accelerate growth. We previously reported that
      cantharidin, an active constituent of a traditional Chinese medicine, potently
      and selectively inhibited PP2A, yet efficiently repressed the growth of
      pancreatic cancer cells through activation of the c-Jun N-terminal kinase (JNK)
      pathway. This suggested that activation of kinase pathways might also be a
      potential strategy for cancer therapy. In this study, we have confirmed that the
      basal activity of the phospatidylinositol 3-kinase (PI3K)/JNK/activator protein 1
      (AP-1) pathway promoted pancreatic cancer cell growth when stimulated by growth
      factors. Interestingly, although treatment with the PP2A inhibitors, cantharidin
      or okadaic acid (OA), amplified the PI3K-dependent activation of JNK, cell growth
      was repressed. We therefore hypothesised that a specific level of activity of the
      JNK pathway might be required to maintain the promitogenic function, as both
      repression and overactivation of JNK could inhibit cell proliferation. It was
      found that the JNK-dependent growth inhibition was independent of the activation
      of AP-1, but dependent on the repression of Akt. Although the PP2A inhibitors
      triggered overactivation of JNK and inhibited cell growth, excessively activated
      protein kinase C (PKC) improved cell survival. Combined treatment with a PP2A
      inhibitor and a PKC inhibitor produced a synergistic effect, which indicates a
      potentially promising therapeutic approach to pancreatic cancer treatment.

PMID- 21958461
TI  - Angiogenesis: a prognostic determinant in pancreatic cancer?
AB  - Angiogenesis has been associated with disease progression in many solid tumours,
      however the statement that tumours need angiogenesis to grow, invade and
      metastasise seems no longer applicable to all tumours or to all tumour subtypes.
      Prognostic studies in pancreatic cancer are conflicting. In fact, pancreatic
      cancer has been suggested an example of a tumour in which angiogenesis is less
      essential for tumour progression. The aim of the present study was therefore to
      measure angiogenesis in two anatomically closely related however prognostically
      different types of pancreatic cancer, pancreatic head and periampullary cancer,
      and investigate its relation with outcome. Vessels were stained by CD31 on
      original paraffin embedded tissue from 206 patients with microscopic radical
      resection (R0) of pancreatic head (n=98) or periampullary cancer (n=108).
      Angiogenesis was quantified by microvessel density (MVD) and measured by
      computerised image analysis of three randomly selected fields and investigated
      for associations with recurrence free survival (RFS), cancer specific survival
      (CSS), overall survival (OS) and conventional prognostic factors. MVD was
      heterogeneous both between and within tumours. A higher MVD was observed in
      periampullary cancers compared with pancreatic head cancers (p<.01). Furthermore,
      MVD was associated with lymph node involvement in pancreatic head (p=.014), but
      not in periampullary cancer (p=.55). Interestingly, MVD was not associated with
      RFS, CSS or with OS. In conclusion, angiogenesis is higher in periampullary
      cancer and although associated with nodal involvement in pancreatic head cancer,
      pancreatic cancer prognosis seems indeed angiogenesis independent.

PMID- 21958458
TI  - Dynorphin is expressed primarily by GABAergic neurons that contain galanin in the
      rat dorsal horn.
AB  - BACKGROUND: The opioid peptide dynorphin is expressed by certain neurons in the
      superficial dorsal horn of the spinal cord, but little is known about the types
      of cell that contain dynorphin. In this study, we have used an antibody against
      the dynorphin precursor preprodynorphin (PPD), to reveal the cell bodies and
      axons of dynorphin-expressing neurons in the rat spinal cord. The main aims were
      to estimate the proportion of neurons in each of laminae I-III that express
      dynorphin and to determine whether they are excitatory or inhibitory neurons.
      RESULTS: PPD-immunoreactive cells were concentrated in lamina I and the outer
      part of lamina II (IIo), where they constituted 17% and 8%, respectively, of all
      neurons. Around half of those in lamina I and 80% of those in lamina II were GABA
      immunoreactive. We have previously identified four non-overlapping neurochemical
      populations of inhibitory interneurons in this region, defined by the presence of
      neuropeptide Y, galanin, parvalbumin and neuronal nitric oxide synthase. PPD co
      localised extensively with galanin in both cell bodies and axons, but rarely or
      not at all with the other three markers. PPD was present in around 4% of
      GABAergic boutons (identified by the presence of the vesicular GABA transporter)
      in laminae I-II. CONCLUSIONS: These results show that most dynorphin-expressing
      cells in the superficial dorsal horn are inhibitory interneurons, and that they
      largely correspond to the population that is defined by the presence of galanin.
      We estimate that dynorphin is present in ~32% of inhibitory interneurons in
      lamina I and 11% of those in lamina II. Since the proportion of GABAergic boutons
      that contain PPD in these laminae was considerably lower than this, our findings
      suggest that these neurons may generate relatively small axonal arborisations.

PMID- 21958466
TI  - Using critical realism as a framework in pharmacy education and social pharmacy
      research.
AB  - This article challenges the idea that positivism is capable of representing the
      complexity of social pharmacy and pharmacy education. It is argued that critical
      realism provides a framework that allows researchers to look at the nature of
      reality and at mechanisms that produce, or have the tendency to produce, events
      and experiences of those events. Critical realism is a framework, not a method.
      It allows researchers to make observations about phenomena and explain the
      relationships and connections involved. The researcher has to look for mechanisms
      and structures that could explain why the phenomena, the connections, and the
      relationships exist (or do not) and then try to show that these mechanisms do
      exist. This article first contextualizes critical realism, then briefly describes
      it, and lastly exemplifies the use of critical realism in a discussion of a
      research project conducted in pharmacy education. Critical realism may be
      particularly useful in interdisciplinary research, for example, where
      practitioners and researchers are working together in a social pharmacy or
      pharmacy education setting. Critical realism requires the practitioners and the
      researchers to question and make known their assumptions about their own
      realities and to think of a complex problem or phenomenon in terms of a
      stratified reality, generative mechanisms, and tendencies. Critical realism may
      make research more rigorous and also allow researchers to conceive of a greater
      breadth of research designs for their work.

PMID- 21958464
TI  - Targeted high throughput sequencing in clinical cancer settings: formaldehyde
      fixed-paraffin embedded (FFPE) tumor tissues, input amount and tumor
      heterogeneity.
AB  - BACKGROUND: Massively parallel sequencing technologies have brought an enormous
      increase in sequencing throughput. However, these technologies need to be further
      improved with regard to reproducibility and applicability to clinical samples and
      settings. METHODS: Using identification of genetic variations in prostate cancer
      as an example we address three crucial challenges in the field of targeted re
      sequencing: Small nucleotide variation (SNV) detection in samples of formalin
      fixed paraffin embedded (FFPE) tissue material, minimal amount of input sample
      and sampling in view of tissue heterogeneity. RESULTS: We show that FFPE tissue
      material can supplement for fresh frozen tissues for the detection of SNVs and
      that solution-based enrichment experiments can be accomplished with small amounts
      of DNA with only minimal effects on enrichment uniformity and data
      variance.Finally, we address the question whether the heterogeneity of a tumor is
      reflected by different genetic alterations, e.g. different foci of a tumor
      display different genomic patterns. We show that the tumor heterogeneity plays an
      important role for the detection of copy number variations. CONCLUSIONS: The
      application of high throughput sequencing technologies in cancer genomics opens
      up a new dimension for the identification of disease mechanisms. In particular
      the ability to use small amounts of FFPE samples available from surgical tumor
      resections and histopathological examinations facilitates the collection of
      precious tissue materials. However, care needs to be taken in regard to the
      locations of the biopsies, which can have an influence on the prediction of copy
      number variations. Bearing these technological challenges in mind will
      significantly improve many large-scale sequencing studies and will - in the long
      term - result in a more reliable prediction of individual cancer therapies.

PMID- 21958469
TI  - Pluripotency of mesenchymal cells derived from synovial fluid in patients with
      temporomandibular joint disorder.
AB  - AIMS: Mesenchymal stem cells are an interesting source of material for
      regenerative medicine. The present study aimed at characterizing the phenotype
      and differentiation potential of adherent synovial fluid-derived cells from
      temporomandibular joint (TMJ) disorder patients. MAIN METHODS: Synovial fluid
      collection takes place during TMJ cavity irrigation arthrocentesis under local
      anesthesia. The synovial fluid-derived adherent cells were fibroblast-like and
      spindle-shaped. Ex vivo-expanded synovial fluid-derived cells were shown to
      express STRO-1 and CD146, previously found to be present in bone marrow
      mesenchymal stem cells. Further, they were identified as being capable of
      differentiating into a variety of cell types including osteoblasts, chondrocytes,
      adipocytes, and neurons. KEY FINDINGS: The present study demonstrates that human
      pluripotent cells can be isolated from synovial fluid. These synovial fluid
      derived cells cannot only be derived from a very accessible resource, but are
      also capable of providing sufficient cells for potential clinical applications.
      SIGNIFICANCE: These cells may play a role in the regenerative response during
      arthritic diseases and are promising candidates for developing novel cell-based
      therapeutic approaches for postnatal skeletal tissue repair.

PMID- 21958463
TI  - Dobutamine administration in patients after cardiac surgery: beneficial or
      harmful?

PMID- 21958468
TI  - The association between hypertension-specific care management processes and blood
      pressure outcomes in US-based physician organizations.
AB  - Care management processes (CMP) may be implemented in health systems to improve
      chronic disease quality of care. The objective of this study was to assess the
      relationship between the presence of hypertension-specific CMP and blood pressure
      (BP) control among hypertensive patients within selected physician organizations
      in the USA-modified version of the Physician Practice Connection Readiness Survey
      (PPC-RS), developed by The National Committee for Quality Assurance (NCQA), was
      administered to chief medical officers at 28 US-based physician organizations in
      2010. Hypertension-specific survey items were added to the PPC-RS and focused on
      medication fill compliance, chronic disease management, and patient self
      management. Demographic and clinical cross-sectional data from a random sample of
      300 hypertensive patients age 18 years or older were collected at each site.
      Physician site and patient characteristics were reported. Regression models were
      used to assess the relationship between hypertension-specific physician practices
      and patient BP control. Eligible patients had at least a 1-year history of care
      with the physician organization and had an encounter within the past year of data
      collection. Of the 28 participating sites, most had electronic medical records
      that handle total functionality (71.4%) and had more than 50 staff members
      (78.6%). Across all sites, approximately 61% of patients had controlled BP.
      Regression analyses found that practices that used physician education as an
      effort to improve medication fill compliance demonstrated improvement in BP
      control (changes in systolic BP: beta coefficient = -1.366, P = .034; changes in
      diastolic BP: beta coefficient = -0.859, P = .056). The use of a systematic
      process to screen or assess patients for hypertension as a risk factor was also
      found to be associated with improvements in BP control (changes in diastolic BP:
      beta coefficient = -0.860, P = .006). In addition, physician practices that
      maintained a list of hypertensive patients along with the patients' associated
      clinical data demonstrated better BP control (currently controlled BP: beta
      coefficient = 0.282, P = .034; currently uncontrolled BP: beta coefficient = 
      0.292, P = .023). However, use of the following practices had a negative
      correlation with BP control: case management (changes in systolic BP: beta
      coefficient 1.649, P = .022; changes in diastolic BP: beta coefficient = 0.910, P
      = .078), follow-up for missed appointments (changes in systolic BP: beta
      coefficient = 0.937, P = .041; changes in diastolic BP: beta coefficient = 0.165,
      P = .627), adopted written evidence-based standards of care to treat hypertension
      (changes in systolic BP: beta coefficient = 0.985, P = .032; changes in diastolic
      BP: beta coefficient = 0.346, P = .305), and checklists for tests and
      interventions (changes in systolic BP: beta coefficient = 1.586, P = .004;
      changes in diastolic BP: beta coefficient = 0.938, P = .019). Findings from this
      multisite study provide evidence that the presence of some hypertension-specific
      CMP in physician organizations may be associated with better BP outcomes among
      hypertensive patients. In particular, patients may benefit from physician efforts
      to improve medication fill compliance as well as organizational monitoring of
      hypertensive patients and their clinical data. Further research is warranted to
      better assess the relationship between CMP and treatment of chronic diseases such
      as hypertension over time.

PMID- 21958467
TI  - Organizational factors influencing pharmacy practice change.
AB  - BACKGROUND: Some pharmacists have changed the focus of their practice from solely
      dispensing. Emerging services they have added include medication therapy
      management and other pharmacy services. OBJECTIVE: To assess the effect of
      entrepreneurial orientation, resource adequacy, and pharmacy staffing on pharmacy
      practice change. METHODS: A total of 1847 licensed U.S. pharmacists received 2
      mail surveys as part of a larger national pharmacist survey. The core survey
      collected information about practice setting, prescription volume, and staffing.
      The supplemental survey assessed how the pharmacy had changed over the past 2
      years to enable the delivery of pharmacy services. The amount of change was
      assessed by 12 items, which were summed to provide an aggregate change index.
      Five variables from organizational change literature were assessed as influences
      on practice change: proactiveness, risk taking, autonomy, work ethic, and
      adequacy of resources. In addition, the associations of pharmacist and technician
      staffing with practice change were assessed. A multiple linear regression
      analysis was performed with the aggregate change index as the dependent variable
      and the 7 potential influences on change as the independent variables. RESULTS:
      Four hundred usable surveys were analyzed. At least some level of practice change
      was reported in 60% of pharmacies surveyed. The linear regression analysis of the
      model was significant (P<.001) with an R-square value of 0.276. Significant
      influences on change were 2 dimensions of entrepreneurial orientation
      proactiveness and autonomy-as well as adequacy of resources and pharmacy
      technician staffing. CONCLUSIONS: Many pharmacies reported that some aspects of
      their practice have changed, such as collecting patient information and
      documenting care. Few reported changes in asking patients to pay for pharmacy
      services. These findings support previous results, which show that the capacity
      for organizational change can be augmented by increasing proactiveness, autonomy
      among employees, and the availability of adequate and appropriate resources.

PMID- 21958471
TI  - Effect of Lactobacillus plantarum and L-arginine against endotoxin-induced liver
      injury in a rat model.
AB  - AIMS: Use of probiotics, alone or as adjunct to other established therapies, has
      been reported to have potential benefits. Recently, we have reported protective
      potential of probiotic against Salmonella-induced liver injury. However, co
      supplementation with prebiotics did not result in meaningful synergism at
      systemic level. Owing to the action of probiotics at the mucosal level and of
      arginine at systemic level, the present study was designed to evaluate the effect
      of Lactobacillus plantarum alone or in conjunction with arginine to combat
      endotoxin-mediated liver injury in rats. MAIN METHODS: Bacterial
      endotoxin/lipopolysaccharide (LPS) was injected intraperitoneally and animals
      were sacrificed 8h post-challenge. Efficacy of L. plantarum alone or in
      conjunction with l-arginine was determined on the basis of enzyme markers,
      histology, levels of nitric oxide (NO) and tumor necrosis factor-alpha (TNF
      alpha) in addition to identification of amino acids by paper chromatography. KEY
      FINDINGS: Prior supplementation of LPS-challenged rats with L. plantarum
      (10(10)CFU per rat given orally for 10 days) demonstrated decreased levels of
      liver enzymes, NO and TNF-alpha. Interestingly, complementing Lactobacillus with
      arginine revealed a synergistic decrease not only in the liver markers but also
      in NO and TNF-alpha along with increased intensity of ornithine and methionine.
      Histological evidence also confirmed the protective efficacy of probiotic in
      conjunction with l-arginine. SIGNIFICANCE: Presence of ornithine and methionine
      in the probiotic-arginine co-supplemented group suggests involvement of arginase
      induced synthesis of polyamines. This study highlights that L. plantarum may
      direct l-arginine metabolism towards polyamine synthesis thereby exhibiting
      synergistic effect against liver injury.

PMID- 21958470
TI  - Reactive oxygen and nitrogen species modulate the ex-vivo effects of LPS on
      platelet adhesion to fibrinogen.
AB  - AIMS: Excessive production of nitric oxide (NO) and reactive oxygen species (ROS)
      in sepsis modulates different cell functions. Since the sepsis severity is
      associated with the degree of platelet activation, we decided to investigate the
      role of systemic generation of NO and ROS in modulating the platelet adhesion of
      lipopolysaccharide (LPS)-treated rats. MAIN METHODS: Platelet adhesion was
      evaluated using fibrinogen-coated 96-well microtiter plates. Cyclic GMP levels
      were measured using enzyme immunoassay kit. KEY FINDINGS: Treatment of rats with
      LPS significantly increased spontaneous platelet adhesion, but reduced the
      thrombin-activated platelet adhesion when compared with control rats. Chronic
      treatment of rats with the NO synthase inhibitor L-NAME (20 mg/rat/day, 7 days)
      prior to LPS injection normalized the increased adhesion in non-activated
      platelets, but failed to affect the adhesion in thrombin-activated platelets. The
      cGMP levels were modified neither in non-activated nor in thrombin-activated
      platelets of LPS-treated rats when compared with control rats. The incubation of
      non-activated platelets with the O2- scavenger PEG-SOD reversed the stimulatory
      effect of LPS on spontaneous adhesion, but had no effect in stimulated-platelet
      adhesion of non-treated or LPS-treated groups. Moreover, pretreatment of rats
      with the antioxidant N-acetylcysteine (NAC; 150 mg/kg) prevented the increase of
      non-activated platelet adhesion, and significantly reduced the inhibitory effect
      of LPS on thrombin-stimulated adhesion. SIGNIFICANCE: Our findings suggest that
      in LPS-treated rats, NO plays an important modulatory role only in non-stimulated
      platelet adhesion through cGMP-independent mechanisms, while ROS, directly or by
      affecting the redox state of the animals, modulates both non-activated and
      thrombin-activated platelet adhesion.

PMID- 21958472
TI  - The value of FDG positron emission tomography/computerised tomography (PET/CT) in
      pre-operative staging of colorectal cancer: a systematic review and economic
      evaluation.
AB  - OBJECTIVES: In the UK, colorectal cancer (CRC) is the third most common
      malignancy (behind lung and breast cancer) with 37,514 cases registered in 2006:
      around two-thirds (23,384) in the colon and one-third (14,130) in the rectum.
      Treatment of cancers of the colon can vary considerably, but surgical resection
      is the mainstay of treatment for curative intent. Following surgical resection,
      there is a comprehensive assessment of the tumour, it's invasion characteristics
      and spread (tumour staging). A number of imaging modalities are used in the pre
      operative staging of CRCs including; computerised tomography (CT), magnetic
      resonance imaging, ultrasound imaging and positron emission tomography (PET).
      This report examines the role of CT in combination with PET scanning (PET/CT
      'hybrid' scan). The research objectives are: to evaluate the diagnostic accuracy
      and therapeutic impact of fluorine-18-deoxyglucose (FDG) PET/CT for the pre
      operative staging of primary, recurrent and metastatic cancer using systematic
      review methods; undertake probabilistic decision-analytic modelling (using Monte
      Carlo simulation); and conduct a value of information analysis to help inform
      whether or not there is potential worth in undertaking further research. DATA
      SOURCES: For each aspect of the research - the systematic review, the handsearch
      study and the economic evaluation - a database was assembled from a comprehensive
      search for published and unpublished studies, which included database searches,
      reference lists search and contact with experts. In the systematic review
      prospective and retrospective patient series (diagnostic cohort) and randomised
      controlled trials (RCTs) were eligible for inclusion. Both consecutive series and
      series that are not explicitly reported as consecutive were included. REVIEW
      METHODS: Two reviewers extracted all data and applied the criteria independently
      and resolved disagreements by discussion. Data to populate 2 * 2 contingency
      tables consisting of the number of true positives, true negatives, false
      positives and false negatives using the studies' own definitions were extracted,
      as were data relating to changes in management. Fourteen items from the Quality
      Assessment of Diagnostic Accuracy Studies checklist were used to assess the
      methodological quality of the included studies. Patient-level data were used to
      calculate sensitivity and specificity with confidence intervals (CIs). Data were
      plotted graphically in forest plots. For the economic evaluation, economic models
      were designed for each of the disease states: primary, recurrent and metastatic.
      These were developed and populated based on a variety of information sources (in
      particular from published data sources) and literature, and in consultation with
      clinical experts. RESULTS: The review found 30 studies that met the eligibility
      criteria. Only two small studies evaluated the use of FDG PET/CT in primary CRC,
      and there is insufficient evidence to support its routine use at this time. The
      use of FDG PET/CT for the detection of recurrent disease identified data from
      five retrospective studies from which a pooled sensitivity of 91% (95% CI 0.87%
      to 0.95%) and specificity of 91% (95% CI 0.85% to 0.95%) were observed. Pooled
      accuracy data from patients undergoing staging for suspected metastatic disease
      showed FDG PET/CT to have a pooled sensitivity of 91% (95% CI 87% to 94%) and a
      specificity of 76% (95% CI 58% to 88%), but the poor quality of the studies means
      the validity of the data may be compromised by several biases. The separate
      handsearch study did not yield any additional unique studies relevant to FDG
      PET/CT. Models for recurrent disease demonstrated an incremental cost
      effectiveness ratio of L 21,409 per quality-adjusted life-year (QALY) for rectal
      cancer, L 6189 per QALY for colon cancer and L 21,434 per QALY for metastatic
      disease. The value of handsearching to identify studies of less clearly defined
      or reported diagnostic tests is still to be investigated. CONCLUSIONS: The
      systematic review found insufficient evidence to support the routine use of FDG
      PET/CT in primary CRC and only a small amount of evidence supporting its use in
      the pre-operative staging of recurrent and metastatic CRC, and, although FDG
      PET/CT was shown to change patient management, the data are divergent and the
      quality of research is generally poor. The handsearch to identify studies of less
      clearly defined or reported diagnostic tests did not find additional studies. The
      primary limitations in the economic evaluations were due to uncertainty and lack
      of available evidence from the systematic reviews for key parameters in each of
      the five models. In order to address this, a conservative approach was adopted in
      choosing DTA estimates for the model parameters. Probabilistic analyses were
      undertaken for each of the models, incorporating wide levels of uncertainty
      particularly for the DTA estimates. None of the economic models reported cost
      savings, but the approach adopted was conservative in order to determine more
      reliable results given the lack of current information. The economic evaluations
      conclude that FDG PET/CT as an add-on imaging device is cost-effective in the pre
      operative staging of recurrent colon, recurrent rectal and metastatic disease but
      not in primary colon or rectal cancers. There would be value in undertaking an
      RCT with a concurrent economic evaluation to evaluate the therapeutic impact and
      cost-effectiveness of FDG PET/CT compared with conventional imaging (without PET)
      for the pre-operative staging of recurrent and metastatic CRC.

PMID- 21958473
TI  - Effect of bleaching on tooth discolouration from food colourant in vitro.
AB  - OBJECTIVES: The purpose of this study was to evaluate the effect of bleaching on
      tooth discolouration from neutral food colourant media (NFCM). METHODS: Freshly
      extracted human molar teeth (n = 32) were divided into four groups (n = 8): non
      bleached treatment-NBT, non-bleached control-NBC, bleached treatment-BT and
      bleached control-BC. Bleached teeth specimens were subjected to 20% carbamide
      peroxide bleaching agent for 10h. Colour measurements (pre-test) were done using
      a non-contact spectroradiometer. The teeth specimens were immersed in a neutral
      buffer solution. NBT and BT groups had 0.025% red food colour (Red 40) added to
      the buffer solution. The immersed specimens were incubated for 4h at 37 degrees
      C. Colour was again measured after immersion/incubation (post-test) and after
      subsequent polishing using plain-pumice slurry (post-polish). Differences in CIE
      a* (redness parameter) were analysed by repeated measures ANOVA with Bonferroni
      corrected t-tests for the pairwise comparisons of interest. RESULTS: Tooth
      discolouration was measured as total stain (mean difference in a* between post
      test minus pre-test), extrinsic stain (mean difference in a* post-polish minus
      post-test) and intrinsic stain (mean difference in a* post-polish minus pre-test)
      A statistically significant difference in the mean Deltaa* was observed (P =
      0.009) between staining treatment for bleached and non-bleached teeth. Also, a
      statistically significant difference (P < 0.001) was noted between control and
      treatment groups of bleached teeth that were subjected to staining. CONCLUSIONS:
      Bleaching resulted in total and extrinsic tooth discolouration by the NFCM.
      CLINICAL SIGNIFICANCE: It might be beneficial to avoid highly pigmented foods
      immediately following bleaching in order to optimize the effects of tooth
      whitening.

PMID- 21958474
TI  - Lipid rafts control P2X3 receptor distribution and function in trigeminal sensory
      neurons of a transgenic migraine mouse model.
AB  - BACKGROUND: A genetic knock-in mouse model expressing the R192Q mutation of the
      alpha1-subunit of the Ca(V)2.1 channels frequently found in patients with
      familial hemiplegic migraine shows functional upregulation of ATP-sensitive P2X3
      receptors of trigeminal sensory neurons that transduce nociceptive inputs to the
      brainstem. In an attempt to understand the basic mechanisms linked to the
      upregulation of P2X3 receptor activity, we investigated the influence of the
      lipid domain of these trigeminal sensory neurons on receptor compartmentalization
      and function. RESULTS: Knock-in neurons were strongly enriched with lipid rafts
      containing a larger fraction of P2X3 receptors at membrane level. Pretreatment
      with the Ca(V)2.1 channel blocker omega-agatoxin significantly decreased the
      lipid raft content of KI membranes. After pharmacologically disrupting the
      cholesterol component of lipid rafts, P2X3 receptors became confined to non-raft
      compartments and lost their functional potentiation typically observed in KI
      neurons with whole-cell patch-clamp recording. Following cholesterol depletion,
      all P2X3 receptor currents decayed more rapidly and showed delayed recovery
      indicating that alteration of the lipid raft milieu reduced the effectiveness of
      P2X3 receptor signalling and changed their desensitization process. Kinetic
      modeling could reproduce the observed data when slower receptor activation was
      simulated and entry into desensitization was presumed to be faster. CONCLUSIONS:
      The more abundant lipid raft compartment of knock-in neurons was enriched in P2X3
      receptors that exhibited stronger functional responses. These results suggest
      that the membrane microenvironment of trigeminal sensory neurons is an important
      factor in determining sensitization of P2X3 receptors and could contribute to a
      migraine phenotype by enhancing ATP-mediated responses.

PMID- 21958475
TI  - Postextubation dysphagia is persistent and associated with poor outcomes in
      survivors of critical illness.
AB  - INTRODUCTION: Dysphagia is common among survivors of critical illness who
      required mechanical ventilation during treatment. The risk factors associated
      with the development of postextubation dysphagia, and the effects of dysphagia on
      patient outcomes, have been relatively unexplored. METHODS: We conducted a
      retrospective, observational cohort study from 2008 to 2010 of all patients over
      17 years of age admitted to a university hospital ICU who required mechanical
      ventilation and subsequently received a bedside swallow evaluation (BSE) by a
      speech pathologist. RESULTS: A BSE was performed after mechanical ventilation in
      25% (630 of 2,484) of all patients. After we excluded patients with stroke and/or
      neuromuscular disease, our study sample size was 446 patients. We found that
      dysphagia was present in 84% of patients (n = 374) and classified dysphagia as
      absent, mild, moderate or severe in 16% (n = 72), 44% (n = 195), 23% (n = 103)
      and 17% (n = 76), respectively. In univariate analyses, we found that
      statistically significant risk factors for severe dysphagia included long
      duration of mechanical ventilation and reintubation. In multivariate analysis,
      after adjusting for age, gender and severity of illness, we found that mechanical
      ventilation for more than seven days remained independently associated with
      moderate or severe dysphagia (adjusted odds ratio (AOR) = 2.84 [interquartile
      range (IQR) = 1.78 to 4.56]; P < 0.01). The presence of severe postextubation
      dysphagia was significantly associated with poor patient outcomes, including
      pneumonia, reintubation, in-hospital mortality, hospital length of stay,
      discharge status and surgical placement of feeding tubes. In multivariate
      analysis, we found that the presence of moderate or severe dysphagia was
      independently associated with the composite outcome of pneumonia, reintubation
      and death (AOR = 3.31 [IQR = 1.89 to 5.90]; P < 0.01). CONCLUSIONS: In a large
      cohort of critically ill patients, long duration of mechanical ventilation was
      independently associated with postextubation dysphagia, and the development of
      postextubation dysphagia was independently associated with poor patient outcomes.

PMID- 21958476
TI  - Evaluation of two sets of immunohistochemical and Western blot confirmatory
      methods in the detection of typical and atypical BSE cases.
AB  - BACKGROUND: Three distinct forms of bovine spongiform encephalopathy (BSE),
      defined as classical (C-), low (L-) or high (H-) type, have been detected through
      ongoing active and passive surveillance systems for the disease.The aim of the
      present study was to compare the ability of two sets of immunohistochemical (IHC)
      and Western blot (WB) BSE confirmatory protocols to detect C- and atypical (L-
      and H-type) BSE forms.Obex samples from cases of United States and Italian C-type
      BSE, a U.S. H-type and an Italian L-type BSE case were tested in parallel using
      the two IHC sets and WB methods. RESULTS: The two IHC techniques proved
      equivalent in identifying and differentiating between C-type, L-type and H-type
      BSE. The IHC protocols appeared consistent in the identification of PrPSc
      distribution and deposition patterns in relation to the BSE type examined. Both
      IHC methods evidenced three distinct PrPSc phenotypes for each type of BSE:
      prevailing granular and linear tracts pattern in the C-type; intraglial and
      intraneuronal deposits in the H-type; plaques in the L-type.Also, the two
      techniques gave comparable results for PrPSc staining intensity on the C- and L
      type BSE samples, whereas a higher amount of intraglial and intraneuronal PrPSc
      deposition on the H-type BSE case was revealed by the method based on a stronger
      demasking step.Both WB methods were consistent in identifying classical and
      atypical BSE forms and in differentiating the specific PrPSc molecular weight and
      glycoform ratios of each form. CONCLUSIONS: The study showed that the IHC and WB
      BSE confirmatory methods were equally able to recognize C-, L- and H-type BSE
      forms and to discriminate between their different immunohistochemical and
      molecular phenotypes. Of note is that for the first time one of the two sets of
      BSE confirmatory protocols proved effective in identifying the L-type BSE form.
      This finding helps to validate the suitability of the BSE confirmatory tests for
      BSE surveillance currently in place.

PMID- 21958478
TI  - The first decade of antiretroviral therapy in Africa.
AB  - The past decade has seen remarkable progress in increasing access to
      antiretroviral therapy in resource-limited settings. Early concerns about the
      cost and complexity of treatment were overcome thanks to the efforts of a global
      coalition of health providers, activists, academics, and people living with
      HIV/AIDS, who argued that every effort must be made to ensure access to essential
      care when millions of lives depended on it. The high cost of treatment was
      reduced through advocacy to promote access to generic drugs; care provision was
      simplified through a public health approach to treatment provision; the lack of
      human resources was overcome through task-shifting to support the provision of
      care by non-physicians; and access was expanded through the development of models
      of care that could work at the primary care level. The challenge for the next
      decade is to further increase access to treatment and support sustained care for
      those on treatment, while at the same time ensuring that the package of care is
      continuously improved such that all patients can benefit from the latest
      improvements in drug development, clinical science, and public health.

PMID- 21958479
TI  - [Treatment of diabetes during hospitalization--still a challenge].

PMID- 21958477
TI  - The biobehavioral and neuroimmune impact of low-dose ionizing radiation.
AB  - In the clinical setting, repeated exposures (10-30) to low-doses of ionizing
      radiation (<=200 cGy), as seen in radiotherapy for cancer, causes fatigue. Almost
      nothing is known, however, about the fatigue inducing effects of a single
      exposure to environmental low-dose ionizing radiation that might occur during
      high-altitude commercial air flight, a nuclear reactor accident or a solar
      particle event (SPE). To investigate the short-term impact of low-dose ionizing
      radiation on mouse biobehaviors and neuroimmunity, male CD-1 mice were whole body
      irradiated with 50 cGy or 200 cGy of gamma or proton radiation. Gamma radiation
      was found to reduce spontaneous locomotor activity by 35% and 36%, respectively,
      6 h post irradiation. In contrast, the motivated behavior of social exploration
      was un-impacted by gamma radiation. Examination of pro-inflammatory cytokine gene
      transcripts in the brain demonstrated that gamma radiation increased hippocampal
      TNF-alpha expression as early as 4 h post-irradiation. This was coupled to
      subsequent increases in IL-1RA (8 and 12 h post irradiation) in the cortex and
      hippocampus and reductions in activity-regulated cytoskeleton-associated protein
      (Arc) (24 h post irradiation) in the cortex. Finally, restraint stress was a
      significant modulator of the neuroimmune response to radiation blocking the
      ability of 200 cGy gamma radiation from impairing locomotor activity and altering
      the brain-based inflammatory response to irradiation. Taken together, these
      findings indicate that low-dose ionizing radiation rapidly activates the
      neuroimmune system potentially causing early onset fatigue-like symptoms in mice.

PMID- 21958480
TI  - [Critically ill children--should parents be present?].

PMID- 21958481
TI  - [Parental presence during treatment of injured and acutely ill children].
AB  - This review studies the literature on the effects of parental presence during
      treatment of injured and acutely ill children. Parents wish to stay with their
      child, and clinicians increasingly find it beneficial, probably correlated with
      increased experience. Studies indicate that the treatment of the child is not
      compromised by parental presence but only a few quasi-randomised, quantitative
      studies have been published, and many circumstances concerning parental presence
      have not been investigated sufficiently.

PMID- 21958482
TI  - [It is uncertain if caesarean section is a risk factor to the development of
      asthma].
AB  - In Denmark the prevalence of both asthma and caesarean section has increased
      during the last 20 years. This review investigates the coherence between
      caesarean section and the development of asthma. Twelve epidemiological articles
      about children over three years were included. Eight of 12 studies discovered no
      association between caesarean section and asthma. There is no difference in the
      quality of the studies. We can conclude that it is uncertain if caesarean section
      is a risk factor to the development of asthma, but it cannot be eliminated that
      asthma is one of many consequences of caesarean section.

PMID- 21958483
TI  - [Surgical reinnervation with nerve anastomosis technique for neurogenic bladder
      and bowel dysfunction].
AB  - Neurogenic bladder and bowel dysfunction are among the major problems faced by
      patients with spinal cord injury and myelomeningocele. New treatment modalities
      enforcing more natural patient control of voiding and defecation are therefore
      appealing. We present a historical review of crossover surgery as treatment for
      such deficiencies and, further, describe the principles as well as the
      documentation for modern surgical intervention in the form of a somato-autonomic
      reflex arch.

PMID- 21958484
TI  - [High risk of suicide among psychiatric patients].
AB  - Suicide rates in Denmark have declined since 1980 both in the general population
      and among psychiatric patients. In recent years, the number of suicides in
      Denmark has been rather stable with approximately 650 incidents each year.
      Register-based studies indicate that half of those who commit suicide have had at
      least one psychiatric admission in the past, and the risk of suicide is
      approximately twentyfold increased in psychiatric patients compared to the risk
      in the general population with only a modest variation across diagnoses. The most
      important risk factor for suicide among psychiatric patients is previous suicide
      attempt. A crisis plan developed together with the patient can be helpful.
      Regular screening for risk of suicide should be implemented in psychiatric
      services.

PMID- 21958485
TI  - [Perforation of the eardrum caused by child abuse].
AB  - Munchausen syndrome by proxy (MSBP) is a complex, multifaceted form of child
      abuse that presents a challenge to all health-care providers. Diagnosis is
      difficult in cases of MSBP, and it is imperative to recognise the clinical
      features of MSBP in both the child and the perpetrator. All members of the health
      care team must stay objective in the interactions with families where MSBP is
      suspected and make referrals to the proper agencies. A case is presented to
      explain the medical and social complexities associated with nursing and
      diagnosing MSBP. This article also provides a brief review of the definition of
      MSBP.

PMID- 21958486
TI  - [Adrenal insufficiency secondary to the use of inhaled corticosteroids].
AB  - Symptomatic adrenal insufficiency secondary to the use of inhaled corticosteroids
      is a rare condition. We present a case in which a 16 year-old male patient with
      asthma treated with high dose fluticasone (1,000 microgram/d) was admitted with
      septicaemia and concomitant adrenal insufficiency. Further investigations
      revealed isolated adrenocorticotropic hormone deficiency most probably caused by
      inhalation of fluticasone. The diagnosis was initially delayed because of
      treatment of the underlying infection. The case serves as a memento that adrenal
      insufficiency should always be borne in mind when it comes to patients treated
      with corticosteroids in any form.

PMID- 21958487
TI  - [Sinus thrombosis in a healthy female taking oral contraceptives].
AB  - A 19 year-old female presented with sudden onset of severe headache and
      photophobia. Clinical examination, blood tests and lumbar puncture were
      unremarkable.The patient was taking drospirenone/ethinyl estradiol oral
      contraceptives. An unenhanced computed tomography (CT) was performed with
      findings suspicious for sinus thrombosis. A confirmatory CT venography was made,
      which was diagnostic for sinus thrombosis. Thrombophilia screening was performed
      and showed normal values. Estrogen-containing hormonal contraceptives was the
      only risk factor, and this therapy has venous thrombosis as a rare side effect.

PMID- 21958488
TI  - [Primary cutaneous cryptococcosis in a pigeon breeder].
AB  - A Danish 73 year-old male patient with polymyalgia rheumatica and in prednisone
      treatment presented with a cutaneous ulcer on the hand caused by a scratch from a
      pigeon. Initial treatment with antibiotics was unsuccessful. Biopsy revealed
      Cryptococcus neoformans and the patient recovered on antifungal treatment.
      Primary cutaneous cryptococcosis is a rare manifestation of a C. neoformans
      infection. This case exemplifies the importance of differential diagnosis in
      immunosuppressed patients who do not respond to a given treatment.

PMID- 21958489
TI  - [Complete remission of diffuse large B-cell lymphoma of the stomach after
      eradication of Helicobacter pylori].
AB  - A 91 year-old man was found to have diffuse large cell B-cell lymphoma (DLBCL),
      localized to the stomach. Because of his age, his only treatment was anti
      Helicobacter pylori therapy. He achieved a complete remission, and six months
      after the initial presentation, there were no signs of recurrence. The
      recommended treatment of DLBCL is chemotherapy followed by involved-field
      irradiation. However, small prospective trials have shown high rates of complete
      remission after eradication of H. pylori alone and this treatment is an option in
      patients of advanced age or with severe co-morbidities.

PMID- 21958490
TI  - [Aicardi syndrome as cause of severe epilepsy and mental retardation].
AB  - Aicardi syndrome is a very rare disease. It is characterised by a triad of
      callosal agenesis, infantile spasms and chorioretinal lacunae. Other congenital
      defects of the eyes, ribs and vertebrae and other malformations also occur
      frequently. Mental retardation and usually intractable seizures are constant
      features. Treatment is only symptomatic and the outcome is very severe in most
      cases. This case report describes a newly diagnosed patient with Aicardi
      syndrome. To our knowledge it is the second case diagnosed in Denmark.

PMID- 21958491
TI  - [Picture of the month: posterior reversible encephalopathy syndrome].

PMID- 21958492
TI  - Major sources of critical incidents in intensive care.
AB  - INTRODUCTION: In recent years, critical incident (CI) reporting has increasingly
      been regarded as part of ongoing quality management. CI databanks also aim to
      improve health and safety issues for patients as well as staff. The aim of this
      study was to identify frequent causes of adverse events in critical care with the
      potential to harm patients, staff or visitors by analysing data from a voluntary
      and optionally anonymous critical incident reporting system. METHODS: The study
      includes all critical incidents reported during a 90-month period in a 13-bed
      adult general intensive care unit (ICU). Reporting of incidents was performed via
      an electronic reporting system or by a manual critical incident report. All CIs
      were classified in the following main categories: equipment, administration,
      pharmaceuticals, clinical practice, and health & safety hazards. The overall
      distribution of incidents within the different categories was compared with the
      regional database of ICUs in the Cheshire and Mersey region of northwest England
      for 2008. RESULTS: A total of 1127 CIs were reported during the study period. The
      frequencies within the main categories were: equipment 338 (30%), clinical
      practice 257 (22.8%), pharmaceuticals 238 (21.1%), administration 213 (18.9%),
      health and safety hazards 81 (7.2%). The regional database had a similar
      frequency of critical incidents within the different categories, suggesting that
      our results may reflect a general distribution pattern of CIs in intensive care.
      CONCLUSIONS: Critical incident reporting helps to identify frequent causes of
      adverse events in critical care. Improvements in quality of care following
      implementation of preventative strategies such as introduction of regular
      equipment training sessions will have to be assessed further in future studies.

PMID- 21958493
TI  - Characterization of simple sequence repeats (SSRs) from Phlebotomus papatasi
      (Diptera: Psychodidae) expressed sequence tags (ESTs).
AB  - BACKGROUND: Phlebotomus papatasi is a natural vector of Leishmania major, which
      causes cutaneous leishmaniasis in many countries. Simple sequence repeats (SSRs),
      or microsatellites, are common in eukaryotic genomes and are short, repeated
      nucleotide sequence elements arrayed in tandem and flanked by non-repetitive
      regions. The enrichment methods used previously for finding new microsatellite
      loci in sand flies remain laborious and time consuming; in silico mining, which
      includes retrieval and screening of microsatellites from large amounts of
      sequence data from sequence data bases using microsatellite search tools can
      yield many new candidate markers. RESULTS: Simple sequence repeats (SSRs) were
      characterized in P. papatasi expressed sequence tags (ESTs) derived from a public
      database, National Center for Biotechnology Information (NCBI). A total of 42,784
      sequences were mined, and 1,499 SSRs were identified with a frequency of 3.5% and
      an average density of 15.55 kb per SSR. Dinucleotide motifs were the most common
      SSRs, accounting for 67% followed by tri-, tetra-, and penta-nucleotide repeats,
      accounting for 31.1%, 1.5%, and 0.1%, respectively. The length of microsatellites
      varied from 5 to 16 repeats. Dinucleotide types; AG and CT have the highest
      frequency. Dinucleotide SSR-ESTs are relatively biased toward an excess of (AX)n
      repeats and a low GC base content. Forty primer pairs were designed based on
      motif lengths for further experimental validation. CONCLUSION: The first large
      scale survey of SSRs derived from P. papatasi is presented; dinucleotide SSRs
      identified are more frequent than other types. EST data mining is an effective
      strategy to identify functional microsatellites in P. papatasi.

PMID- 21958495
TI  - Reprint of: chip-based nanoelectrospray mass spectrometry of brain gangliosides.
AB  - In the past few years, a considerable effort was invested in interfacing mass
      spectrometry (MS) to microfluidics-based systems for electrospray ionization
      (ESI). Since its first introduction in biological mass spectrometry, chip-based
      ESI demonstrated a high potential to discover novel structures of biomarker
      value. Therefore, recently, microfluidics for electrospray in conjunction with
      advanced MS instruments able to perform multistage fragmentation were introduced
      also in glycolipid research. This review is focused on the strategies, which
      allowed a successful application of chip technology for ganglioside mapping and
      sequencing by ESI MS and tandem MS (MS/MS). The first part of the review is
      dedicated to the progress of MS methods in brain ganglioside research, which
      culminated with the introduction of two types of microfluidic devices: the
      NanoMate robot and a polymer microchip for electrospray. In the second part a
      systematic description of most relevant results obtained by using MS in
      combination with the two chip systems is presented. Chip-based ESI
      accomplishments for determination of ganglioside expression and structure in
      normal brain regions and brain pathologies such as neurodegenerative diseases and
      primary brain tumors are described together with some considerations upon the
      perspectives of microfluidics-MS to be routinely introduced in biomedical
      investigation.

PMID- 21958494
TI  - Meropenem vs standard of care for treatment of late onset sepsis in children of
      less than 90 days of age: study protocol for a randomised controlled trial.
AB  - BACKGROUND: Late onset neonatal sepsis (LOS) with the mortality of 17 to 27% is
      still a serious disease. Meropenem is an antibiotic with wide antibacterial
      coverage. The advantage of it over standard of care could be its wider
      antibacterial coverage and thus the use of mono-instead of combination therapy.
      METHODS: NeoMero-1, an open label, randomised, comparator controlled, superiority
      trial aims to compare the efficacy of meropenem with a predefined standard of
      care (ampicillin + gentamicin or cefotaxime + gentamicin) in the treatment of LOS
      in neonates and infants aged less than 90 days admitted to a neonatal intensive
      care unit.A total of 550 subjects will be recruited following a 1:1 randomisation
      scheme. The trial includes patients with culture confirmed (at least one positive
      culture from normally sterile site except coagulase negative staphylococci in
      addition to one clinical or laboratory criterion) or clinical sepsis (at least
      two laboratory and two clinical criteria suggestive of LOS in subjects with
      postmenstrual age < 44 weeks or fulfilment of criteria established by the
      International Pediatric Sepsis Consensus Conference in subjects with
      postmenstrual age >= 44 weeks). Meropenem will be given at a dose of 20 mg/kg
      q12h or q8h depending on the gestational- and postnatal age. Comparator agents
      are administered as indicated in British National Formulary for Children. The
      primary endpoint measured at the test of cure visit (2 days after end of study
      therapy) is graded to success (all baseline symptoms and laboratory parameters
      are resolved or improved with no need to continue antibiotics and the baseline
      microorganisms are eradicated and no new microorganisms are identified and the
      patient has received allocated treatment for 11 +/- 3 days with no modification)
      or a failure (all remaining cases). Secondary outcome measures include comparison
      of survival, relapse rates or new infections by Day 28, clinical response at Day
      3 and end of therapy, duration of hospitalisation, population pharmacokinetic
      analysis of meropenem and effect of antibiotics on mucosal colonisation and
      development of antibacterial resistance.The study will start recruitment in
      September 2011; the total duration is of 24 months. TRIAL REGISTRATION: EudraCT
      2011-001515-31.

PMID- 21958496
TI  - Striking a balance between idealism and fatalism.

PMID- 21958497
TI  - ...And the only side-effects are good ones.

PMID- 21958498
TI  - Challenges related to palliative care.

PMID- 21958499
TI  - Paediatric oncology: are there ways to bend the costs?

PMID- 21958500
TI  - Caring for patients with haematological malignancies.

PMID- 21958501
TI  - Regulators, payers, and prescribers: can we fill the gaps?

PMID- 21958502
TI  - The opportunity cost of cancer care: a statement from NICE.

PMID- 21958503
TI  - Delivering affordable cancer care in high-income countries.
AB  - The burden of cancer is growing, and the disease is becoming a major economic
      expenditure for all developed countries. In 2008, the worldwide cost of cancer
      due to premature death and disability (not including direct medical costs) was
      estimated to be US$895 billion. This is not simply due to an increase in absolute
      numbers, but also the rate of increase of expenditure on cancer. What are the
      drivers and solutions to the so-called cancer-cost curve in developed countries?
      How are we going to afford to deliver high quality and equitable care? Here,
      expert opinion from health-care professionals, policy makers, and cancer
      survivors has been gathered to address the barriers and solutions to delivering
      affordable cancer care. Although many of the drivers and themes are specific to a
      particular field-eg, the huge development costs for cancer medicines-there is
      strong concordance running through each contribution. Several drivers of cost,
      such as over-use, rapid expansion, and shortening life cycles of cancer
      technologies (such as medicines and imaging modalities), and the lack of suitable
      clinical research and integrated health economic studies, have converged with
      more defensive medical practice, a less informed regulatory system, a lack of
      evidence-based sociopolitical debate, and a declining degree of fairness for all
      patients with cancer. Urgent solutions range from re-engineering of the
      macroeconomic basis of cancer costs (eg, value-based approaches to bend the cost
      curve and allow cost-saving technologies), greater education of policy makers,
      and an informed and transparent regulatory system. A radical shift in cancer
      policy is also required. Political toleration of unfairness in access to
      affordable cancer treatment is unacceptable. The cancer profession and industry
      should take responsibility and not accept a substandard evidence base and an
      ethos of very small benefit at whatever cost; rather, we need delivery of fair
      prices and real value from new technologies.

PMID- 21958505
TI  - Prevalence of overactive bladder and associated risk factors in 1359 patients
      with type 2 diabetes.
AB  - OBJECTIVE: To evaluate overactive bladder (OAB, dry and wet) and the associated
      risk factors of OAB wet (with incontinence) in type 2 diabetes. METHODS: A self
      administered questionnaire containing the OAB symptom score (OABSS, 0-15, with
      higher numbers indicating an increasing severity of symptoms) was obtained from
      subjects with type 2 diabetes at a dedicated diabetic center. The association of
      age, sex, duration of diabetes, body mass index, waist circumference, glycated
      hemoglobin level, high-sensitive C-reactive protein level, and diabetes
      associated complications to the risk of OAB and OAB wet was evaluated. RESULTS:
      Of 1359 consecutive subjects, 22.5% reported having OAB, with 11.7% reporting OAB
      dry and 10.8% OAB wet. The difference in symptom severity was statistically
      significant among those without OAB and those with OAB dry and OAB wet (OABSS 2.5
      +/- 1.4, 5.9 +/- 1.6, and 8.9 +/- 2.6, respectively). The prevalence of OAB and
      OAB wet was 2.4-fold and 4.2-fold greater, respectively, in patients with a
      diabetes duration >10 years and age >50 years. Age and male sex and age and waist
      circumference were independent risk factors for OAB and OAB wet, respectively,
      after multivariate analysis. Glycated hemoglobin and high-sensitivity C-reactive
      protein levels were similar between patients with diabetes patients with and
      without OAB. CONCLUSION: In the dedicated diabetic center in which all patients
      were screened, 22.5% had OAB, and 48.0% of those with OAB had incontinence. These
      findings can help guide the collaboration between urologists and diabetologists
      to work toward developing screening for, and early treatment of, urologic
      complications in higher risk patients.

PMID- 21958504
TI  - Plasma from septic shock patients induces loss of muscle protein.
AB  - INTRODUCTION: ICU-acquired muscle weakness commonly occurs in patients with
      septic shock and is associated with poor outcome. Although atrophy is known to be
      involved, it is unclear whether ligands in plasma from these patients are
      responsible for initiating degradation of muscle proteins. The aim of the present
      study was to investigate if plasma from septic shock patients induces skeletal
      muscle atrophy and to examine the time course of plasma-induced muscle atrophy
      during ICU stay. METHODS: Plasma was derived from septic shock patients within 24
      hours after hospital admission (n = 21) and healthy controls (n = 12). From nine
      patients with septic shock plasma was additionally derived at two, five and seven
      days after ICU admission. These plasma samples were added to skeletal myotubes,
      cultured from murine myoblasts. After incubation for 24 hours, myotubes were
      harvested and analyzed on myosin content, mRNA expression of E3-ligase and
      Nuclear Factor Kappa B (NFkappaB) activity. Plasma samples were analyzed on
      cytokine concentrations. RESULTS: Myosin content was approximately 25% lower in
      myotubes exposed to plasma from septic shock patients than in myotubes exposed to
      plasma from controls (P < 0.01). Furthermore, patient plasma increased expression
      of E3-ligases Muscle RING Finger protein-1 (MuRF-1) and Muscle Atrophy F-box
      protein (MAFbx) (P < 0.01), enhanced NFkappaB activity (P < 0.05) and elevated
      levels of ubiquitinated myosin in myotubes. Myosin loss was significantly
      associated with elevated plasma levels of interleukin (IL)-6 in septic shock
      patients (P < 0.001). Addition of antiIL-6 to septic shock plasma diminished the
      loss of myosin in exposed myotubes by approximately 25% (P < 0.05). Patient
      plasma obtained later during ICU stay did not significantly reduce myosin content
      compared to controls. CONCLUSIONS: Plasma from patients with septic shock induces
      loss of myosin and activates key regulators of proteolysis in skeletal myotubes.
      IL-6 is an important player in sepsis-induced muscle atrophy in this model. The
      potential to induce atrophy is strongest in plasma obtained during the early
      phase of human sepsis.

PMID- 21958506
TI  - Identification and characterization of six novel tetraspanins from Schistosoma
      japonicum.
AB  - BACKGROUND: Tetraspanins (TSPs), also known as members of the trans-membrane 4
      super-family (TM4SF), comprise an assemblage of surface antigens reported in
      eukaryotic organisms. In the work presented here, six novel TSP proteins from the
      human blood fluke Schistosoma japonicum (S. japonicum) were produced and analyzed
      through a combination of bioinformatics and experimental approaches. RESULTS: Six
      novel TSP proteins of Schistosoma japonicum (designated as Sj-TSP-#1~6) contained
      four trans-membrane regions and one large extracellular loop (LEL) with a
      conserved CCG motif. Size of the proteins varied from 227 to 291 amino acid
      residues. All the six proteins were produced in E.coli and immune sera to each
      protein were prepared. Analysis of transcription profiles of the proteins by RT
      PCR showed that Sj-TSP-#4 was transcribed only in the egg stage while
      transcription of the Sj-TSP-#2 was detected in female worms but not in males. The
      similar results were obtained by Western blot. Immunolocalization of the TSP
      proteins by immunofluorescence assay showed that the Sj-TSP-#2, Sj-TSP-#5 and Sj
      TSP-#6 were located in the tegument of worms. CONCLUSIONS: This study provided
      six novel TSP members of S. japonicum including their sequences and recombinant
      proteins. Availability of the novel proteins and information on their expression
      profile and location provided a basis for further investigation of the TSP
      proteins for their biological functions and as vaccine candidates.

PMID- 21958507
TI  - Immunogenicity and safety of re-exposure to recombinant human thrombin in
      surgical hemostasis.
AB  - BACKGROUND: This Phase 4, open-label study evaluated the immunogenicity and
      safety of a second exposure to recombinant human thrombin (rThrombin) in adult
      patients with previous exposure to rThrombin. STUDY DESIGN: Topical rThrombin was
      applied as a hemostatic aid during a surgical procedure (day 1). Adverse events
      and clinical laboratory abnormalities were monitored to day 29 (study end).
      Immunogenicity samples were collected on days 1 and 29. Thirty-one patients were
      treated at 9 study sites; 30 patients completed the study. RESULTS: Mean age was
      59.5 years; 61.3% of patients were male. Study operations types included spinal
      (n = 23 of 31; 74.2%), arterial reconstruction or peripheral arterial bypass (n =
      4; 12.9%), arteriovenous vascular access procedure (n = 3; 9.7%), and other (n =
      1; 3.2%). A median of 10 mL rThrombin (1,000 IU/mL; range 5 to 60 mL) was
      prepared per patient. Median elapsed time since previous rThrombin exposure was
      1.3 years (range 19 days to 3.3 years). Recombinant human thrombin was not
      observed to be immunogenic; no patients (n = 0 of 30, 0%; 95% CI 0.0%, 11.6%)
      became positive for anti-rThrombin product antibodies at day 29, approximately 1
      month after the second exposure to rThrombin. The most commonly reported adverse
      events were procedural pain (n = 23 of 31, 74.2%), constipation (n = 8, 25.8%),
      and nausea (n = 8, 25.8%) All adverse events and clinical laboratory
      abnormalities were considered unrelated to treatment. For the majority of
      patients, maximal severity of any adverse event was mild or moderate.
      CONCLUSIONS: The immunogenicity and safety results of this Phase 4 rThrombin
      trial suggest that patients with known previous exposure may be safely re-exposed
      to topical rThrombin.

PMID- 21958508
TI  - Laparoscopic left hepatectomy with extraparenchymal inflow control.

PMID- 21958510
TI  - Postoperative antibiotics correlate with worse outcomes after appendectomy for
      nonperforated appendicitis.
AB  - BACKGROUND: Acute appendicitis remains the most common cause of acute abdominal
      pain necessitating operative intervention. Although postoperative antibiotics are
      universally used for perforated appendicitis, no consensus exists on whether
      postoperative antibiotics are beneficial for preventing surgical site infections
      (SSIs) in nonperforated cases. We set out to determine how postoperative
      antibiotic therapy affects outcomes after appendectomy for nonperforated
      appendicitis. STUDY DESIGN: The medical records of 1,000 patients undergoing
      appendectomy for nonperforated appendicitis at The Mount Sinai Medical Center
      from January 2005 through July 2010 were retrospectively reviewed. RESULTS: In
      total, 728 cases contained sufficient follow-up data for analysis; 334 of these
      patients received postoperative antibiotics and 394 did not. There were no
      significant differences in patient demographics, medical comorbidities, American
      Society of Anesthesiologists (ASA) class, admission temperature, preoperative
      antibiotic treatment, operating room time, estimated blood loss, appendiceal
      diameter, or intraoperative transfusion between the two groups, although WBC was
      higher for patients receiving postoperative antibiotics (12.3 vs 14 cells/mm(3),
      p = 0.001). Postoperative antibiotics did not alter the incidence of superficial
      SSIs, deep SSIs, or organ space SSIs (all p = 0.1), but did correlate with higher
      rates of Clostridium difficile infection (p = 0.02), urinary tract infection (p =
      0.05), postoperative diarrhea (p < 0.001), and longer length of stay (LOS) (1.1
      vs 2.4 days, p < 0.001). Patients receiving postoperative antibiotics also showed
      trends toward higher readmission and reoperation rates (both p = 0.06).
      CONCLUSIONS: Postoperative antibiotic treatment for nonperforated appendicitis
      did not reduce infectious complications and prolonged LOS while increasing
      postoperative morbidity. Therefore, postoperative antibiotics likely increase the
      treatment cost for nonperforated appendicitis while not adding an appreciable
      clinical benefit and, in some cases, actually worsening outcomes.

PMID- 21958509
TI  - Commonwealth of Massachusetts Board of Registration in Medicine Expert Panel on
      immediate implant-based breast reconstruction following mastectomy for cancer:
      executive summary, June 2011.

PMID- 21958511
TI  - Racial, ethnic, and insurance status disparities in use of posthospitalization
      care after trauma.
AB  - BACKGROUND: Posthospitalization care is important for recovery after trauma.
      Disadvantaged populations, like racial or ethnic minorities and the uninsured,
      make up substantial percentages of trauma patients, but their use of
      posthospitalization facilities is unknown. STUDY DESIGN: This study analyzed
      National Trauma Data Bank admissions from 2007 for 18- to 64-year-olds and
      estimated relative risk ratios (RRR) of discharge to posthospitalization
      facilities--home, home health, rehabilitation, or nursing facility--by race,
      ethnicity, and insurance. Multinomial logistic regression adjusted for patient
      characteristics including age, sex, Injury Severity Score, mechanism of injury,
      and length of stay, among others. RESULTS: There were 136,239 patients who met
      inclusion criteria with data for analysis. Most patients were discharged home
      (78.9%); fewer went to home health (3.3%), rehabilitation (5.0%), and nursing
      facilities (5.4%). When compared with white patients in adjusted analysis,
      relative risk ratios of discharge to rehabilitation were 0.61 (95% CI 0.56, 0.66)
      and 0.44 (95% CI 0.40, 0.49) for blacks and Hispanics, respectively. Compared
      with privately insured white patients, Hispanics had lower rates of discharge to
      rehabilitation whether privately insured (RRR 0.45, 95% CI 0.40, 0.52), publicly
      insured (RRR 0.51, 95% CI 0.42, 0.61), or uninsured (RRR 0.20, 95% CI 0.17,
      0.24). Black patients had similarly low rates: private (RRR 0.63, 95% CI 0.56,
      0.71), public (RRR 0.72, 95% CI 0.63, 0.82), or uninsured (RRR 0.27, 95% CI 0.23,
      0.32). Relative risk ratios of discharge to home health or nursing facilities
      showed similar trends among blacks and Hispanics regardless of insurance, except
      for black patients with insurance whose discharge to nursing facilities was
      similar to their white counterparts. CONCLUSIONS: Disadvantaged populations have
      more limited use of posthospitalization care such as rehabilitation after trauma,
      suggesting a potential improvement in trauma care for the underprivileged.

PMID- 21958512
TI  - Computerized texture analysis of atypical immature myeloid precursors in patients
      with myelodysplastic syndromes: an entity between blasts and promyelocytes.
AB  - BACKGROUND: Bone marrow (BM) blast count is an essential parameter for
      classification and prognosis of myelodysplastic syndromes (MDS). However, a high
      degree of cell atypias in bone marrow hemopoietic cells may be found in this
      group of clonal disorders, making it difficult to quantify precisely myeloblasts,
      and to distinguish them from promyelocytes and atypical immature myeloid
      precursors. Our aim was to investigate whether computerized image analysis of
      routine cytology would help to characterize these cells. METHODS: In May-Grunwald
      Giemsa stained BM smears of 30 newly diagnosed MDS patients and 19 cases of
      normal BM, nuclei of blasts and promyelocytes were digitalized and interactively
      segmented. The morphological classification of the cells was done by consensus of
      two observers. Immature granulocytic precursors, which could not be clearly
      classified either as blasts or promyelocytes, were called "atypic myeloid
      precursors". Nuclear morphometry and texture features derived from the co
      occurrence matrix and fractal dimension (FD) were calculated. RESULTS: In normal
      BM, when compared to myeloblasts, nuclei of promyelocytes showed significant
      increase in perimeter and local texture homogeneity and a decrease in form
      factor, chromatin gray levels, Haralick's entropy, inertia, energy, contrast,
      diagonal moment, cluster prominence, the fractal dimension according to Minkowski
      and its goodness-of-fit. Compared to normal myeloblast nuclei, the chromatin
      texture of MDS myeloblasts revealed higher local homogeneity and goodness-of-fit
      of the FD, but lower values of entropy, contrast, diagonal moment, and fractal
      dimension. The same differences were found between nuclei of normal promyelocytes
      and those of MDS. Nuclei of atypical myeloid precursors showed intermediate
      characteristics between those of blasts and promyelocytes according to the
      quantitative features (perimeter, form factor, gray level and its standard
      deviation), but were similar to promyelocytes according to the texture variables
      inertia, energy, contrast, diagonal moment, cluster prominence, and Minkowski's
      fractal dimension. CONCLUSION: BM atypical immature myeloid precursors are
      difficult to be correctly classified in routine cytology. Although their
      cytoplasm is more similar to that of myeloblasts, computerized texture analysis
      indicates a nuclear chromatin remodeling more close to the promyelocyte, thus
      indicating an asynchronous intermediate maturation stage between blast and
      promyelocyte.

PMID- 21958513
TI  - Evaluation of basal ganglia, brainstem raphe and ventricles in bipolar disorder
      by transcranial sonography.
AB  - Transcranial brain sonography (TCS) has become a reliable and sensitive
      diagnostic tool in the evaluation of extrapyramidal movement disorders.
      Alterations of brainstem raphe (BR) have been depicted by TCS in major depression
      but not in bipolar disorder. The aim of our study was to evaluate BR echogenicity
      depending on the different conditions of bipolar patients. Echogenicities of
      dopaminergic basal ganglia structures were assessed for the first time in bipolar
      disorder. Thirty-six patients with bipolar I disorder (14 depressed, 8 manic, 14
      euthymic) were compared to 35 healthy controls. Echogenicities were investigated
      according to the examination protocol for extrapyramidal disorders using a
      Siemens Sonoline(r) Elegra system. The sonography examiner was blinded for
      clinical rating scores. Six patients (16.7%) showed hyperechogenicity of the
      substantia nigra. The raphe was hypoechogenic in 13 (36.1%) of the patients. No
      significant differences were seen between the subgroups. Compared to the control
      group, frequency of altered echogenicities did not reach statistical
      significance. The width of third ventricle was significantly larger in the
      patient group (3.8+/--2.1 mm vs. 2.7+/-1.2 mm). Depressed bipolar patients with
      reduced BR echogenicity showed significantly higher scores on the Hamilton
      Depression Rating Scale as well as the Montgomery-Asberg Depression Rating Scale.
      In contrast to unipolar depression, sonographic findings of bipolar patients may
      generally indicate structural integrity of mesencephalic raphe structures. If
      bipolar disorder coexists with hypoechogenic raphe structure, depressive symptoms
      are more severe.

PMID- 21958514
TI  - Lower activation in the right frontoparietal network during a counting Stroop
      task in a cocaine-dependent group.
AB  - Dysregulation in cognitive control networks may mediate core characteristics of
      drug addiction. Cocaine dependence has been particularly associated with low
      activation in the frontoparietal regions during conditions requiring decision
      making and cognitive control. This functional magnetic resonance imaging (fMRI)
      study aimed to examine differential brain-related activation to cocaine addiction
      during an inhibitory control paradigm, the "Counting" Stroop task, given the
      uncertainties of previous studies using positron emission tomography. Sixteen
      comparison men and 16 cocaine-dependent men performed a cognitive "Counting"
      Stroop task in a 1.5T Siemens Avanto. The cocaine-dependent patient group and the
      control group were matched for age, level of education and general intellectual
      functioning. Groups did not differ in terms of the interference measures deriving
      from the counting Stroop task. Moreover, the cocaine-dependent group showed lower
      activation in the right inferior frontal gyrus, the right inferior parietal gyrus
      and the right superior temporal gyrus than the control group. Cocaine patients
      did not show any brain area with increased activation when compared with
      controls. In short, Stroop-interference was accompanied by lower activation in
      the right frontoparietal network in cocaine-dependent patients, even in the
      absence of inter-group behavioral differences. Our study is the first application
      of a counting Stroop task using fMRI to study cocaine dependence and yields
      results that corroborate the involvement of a frontoparietal network in the
      neural changes associated with attentional interference deficits in cocaine
      dependent men.

PMID- 21958515
TI  - Tindaro Renda's symposium in honour of his ''maestro'' Vittorio Ersparmer.
      Foreword.

PMID- 21958516
TI  - Motility of Pseudomonas aeruginosa in saturated granular media as affected by
      chemoattractant.
AB  - To examine and quantify the effects of glass beads and chemoattractant on
      bacterial motility in granular media, we examined the motile behavior of P.
      aeruginosa in a saturated granular medium and quantified the effects of glass
      beads and the presence of a chemoattractant. By recording individual cell
      trajectories in microfluidic channels under a high-speed confocal microscope, we
      directly measured the cell's run direction and corresponding run-length, speed
      and turn angle. Bacterial run speed increased in the presence of chemoattractant
      in both aqueous and granular media. But it decreased in glass-beads compared to
      in aqueous media due to the restricted pore geometry and interactions between
      bacteria and grain surfaces. Notably, the relatively higher frequency
      distribution at turn angles of 170 degrees  decreased dramatically, while the
      smaller peak at 70 degrees  increased and became dominant on a bimodal
      distribution, showing more bacteria changed directions at smaller turn angles
      rather than reverse their swimming directions. Additionally, the presence of
      glass beads also decreased the chemotactic velocity and random motility by
      similar proportions due to the restrictive geometry and the interactions between
      bacteria and glass beads surface. Our study indicates that the swimming
      parameters measured from aqueous media cannot be directly adopted in models for
      predicting bacteria travel in granular media.

PMID- 21958517
TI  - Infrared transmission and emission spectroscopic study of selected Chinese
      palygorskites.
AB  - Infrared transmission and emission spectroscopy were used to analyze the
      difference in structure and thermal behavior of two Chinese palygorskites. The
      position of the main bands identified in the infrared spectra of the
      palygorskites studied is similar for these two Chinese samples, but there are
      some differences in their intensity, which is significant. This discrepancy is
      attributed to the existence of impurities and the geological environments in
      different regions. The infrared emission spectra clearly show the structural
      changes and dehydroxylation of the palygorskites when the temperature is raised.
      The dehydration of the palygorskites is followed by the loss of intensity of the
      OH stretching vibration bands in the region of 3600-3200 cm(-1). Dehydroxylation
      is followed by the decrease in intensity in the bands between 3700 and 3550 cm(
      1). Dehydration of pure palygorskite was completed by 600 degrees C. Partial loss
      of coordinated water was observed at 400 degrees C. Infrared emission
      spectroscopy is an effective method to determine the stability of the mineral.

PMID- 21958518
TI  - FT-IR, UV-vis, 1H and 13C NMR spectra and the equilibrium structure of organic
      dye molecule disperse red 1 acrylate: a combined experimental and theoretical
      analysis.
AB  - This study reports the characterization of disperse red 1 acrylate compound by
      spectral techniques and quantum chemical calculations. The spectroscopic
      properties were analyzed by FT-IR, UV-vis, (1)H NMR and (13)C NMR techniques. FT
      IR spectrum in solid state was recorded in the region 4000-400 cm(-1). The UV-vis
      absorption spectrum of the compound that dissolved in methanol was recorded in
      the range of 200-800 nm. The (1)H and (13)C NMR spectra were recorded in CDCl(3)
      solution. The structural and spectroscopic data of the molecule in the ground
      state were calculated using density functional theory (DFT) employing B3LYP
      exchange correlation and the 6-311++G(d,p) basis set. The vibrational wavenumbers
      were calculated and scaled values were compared with experimental FT-IR spectrum.
      A satisfactory consistency between the experimental and theoretical spectra was
      obtained and it shows that the hybrid DFT method is very useful in predicting
      accurate vibrational structure, especially for high-frequency region. The
      complete assignments were performed on the basis of the experimental results and
      total energy distribution (TED) of the vibrational modes, calculated with scaled
      quantum mechanics (SQM) method. Isotropic chemical shifts were calculated using
      the gauge-invariant atomic orbital (GIAO) method. A study on the electronic
      properties were performed by timedependent DFT (TD-DFT) and CIS(D) approach. To
      investigate non linear optical properties, the electric dipole moment MU,
      polarizability alpha, anisotropy of polarizability Deltaalpha and molecular first
      hyperpolarizability beta were computed. The linear polarizabilities and first
      hyperpolarizabilities of the studied molecule indicate that the compound can be a
      good candidate of nonlinear optical materials.

PMID- 21958519
TI  - Vibrational spectral analysis and first hyperpolarizability studies of 1
      bromonaphthalene based on ab initio and DFT methods.
AB  - In this work, the experimental and theoretical vibrational spectra of 1
      bromonaphthalene (1-BN) were studied. FTIR and FT Raman spectra were recorded in
      the region 4000-400 cm(-1) and 3500-50 cm(-1), respectively. The structural and
      spectroscopic data of the molecule in the ground state were calculated by using
      ab initio Hartree-Fock and density functional method (B3LYP) with the 6
      311++G(d,p) basis set. The vibrational frequencies were calculated and scaled
      values were compared with experimental FTIR and FT Raman spectra. The observed
      and calculated frequencies are found to be in good agreement. The complete
      assignments were performed on the basis of the total energy distribution (TED) of
      the vibrational modes, calculated with scaled quantum mechanics (SQM) method. The
      optimized geometric parameters were calculated. The predicted first
      hyperpolarizability also shows that the molecule might have a reasonably good
      nonlinear optical (NLO) behaviour. The calculated HOMO-LUMO energy gap reveals
      that charge transfer occurs within the molecule.

PMID- 21958520
TI  - Secondary hormonal therapy in men with castration-resistant prostate cancer.
AB  - BACKGROUND: Androgen receptor (AR) signaling remains important in castration
      resistant prostate cancer (CRPC) and sequential responses to hormonal therapies
      are observed. Little is known about the factors associated with responsiveness to
      secondary hormone therapy (HT). METHODS: We retrospectively identified patients
      with CRPC who were treated with secondary HT. Patient characteristics and types
      and duration of secondary HT were analyzed. Selected clinical characteristics and
      their association with duration of secondary HT were evaluated. RESULTS: Of 436
      eligible patients, 321 (74%) and 87 (20%) received at least two or four secondary
      HT regimens, respectively. Median duration of time on primary androgen
      deprivation therapy alone (ADT) and secondary HT were 24.0 months (range, 1.5 to
      171.8 months) and 30.3 months (range, 0.6 to 156.1+ months), respectively.
      Patients who received primary ADT >= 24 months received secondary HT for a median
      duration of 40.0 months, whereas men who received ADT < 24 months had a median
      duration of 18.4 months on secondary HT (P < .0001). Metastatic disease at
      secondary HT initiation was associated with a shorter time on secondary HT (P =
      .0001). Patients who received the first secondary HT for >= 6 months were more
      likely to have a longer duration on subsequent secondary HT compared with the men
      who received the first secondary HT < 6 months (P = .0001). CONCLUSIONS:
      Treatment durations of secondary HT are variable. Longer duration of primary ADT
      was associated with longer duration of secondary HT. These results imply that AR
      signaling remains an important therapeutic target in CRPC.

PMID- 21958522
TI  - New insights into tau-microtubules interaction revealed by isothermal titration
      calorimetry.
AB  - Microtubule dynamic instability is tightly regulated by coordinated action of
      stabilizing and destabilizing microtubule associated proteins. Among the
      stabilizing proteins, tau plays a pivotal role in both physiological and
      pathological processes. Nevertheless, the detailed mechanism of tau-tubulin
      interaction is still subject to controversy. In this report, we studied for the
      first time tau binding to tubulin by a direct thermodynamic method in the absence
      of any tubulin polymerization cofactors that could influence this process.
      Isothermal titration calorimetry enabled us to evidence two types of tau-tubulin
      binding modes: one corresponding to a high affinity binding site with a
      tau:tubulin stoichiometry of 0.2 and the other one to a low affinity binding site
      with a stoichiometry of 0.8. The same stoichiometries were obtained at all
      temperatures tested (10-37 degrees C), indicating that the mechanism of
      interaction does not depend on the type of tubulin polymer triggered upon tau
      binding. These findings allowed us to get new insights into the topology of tau
      on microtubules.

PMID- 21958523
TI  - A kinetic analysis and experimental validation of an integrated system of
      anaerobic filter and biological aerated filter.
AB  - An anaerobic/aerobic filter (AF/BAF) system was developed treating dairy
      wastewater. The influent was blended with recirculated effluent to allow for pre
      denitrification in the AF followed by nitrification in the BAF. The recirculation
      ratio ranged 100-300%. The average chemical oxygen demand (COD) removal
      efficiency was 79.8-86.8% in the AF and the average total nitrogen removal
      efficiency was 50.5-80.8% in the AF/BAF system. Steady-state mass balances on the
      AF were used to analyze removal kinetics in the AF. The kinetic model values for
      effluent COD in the AF were overestimated as compared with experimental data. The
      integrated suspended and attached biomass growth rates in the AF were estimated.
      The specific growth rate of the integrated biomass at each recirculation ratios
      was 0.6213, 0.6647, and 1.20831/day, respectively. The increase in specific
      growth rate corresponded to increases in biomass sloughing as the recirculation
      ratio increased.

PMID- 21958521
TI  - Pilot trial of bone-targeted therapy combining zoledronate with fluvastatin or
      atorvastatin for patients with metastatic renal cell carcinoma.
AB  - BACKGROUND: The biological rationale for this study came from the observation
      that bisphosphonates and statins affect bone metastasis in different ways and
      thus combination therapy may provide synergistic benefit. This pilot trial
      evaluated the efficacy and safety of combining a bisphosphonate and a statin in
      patients with RCC metastatic to bone. METHODS: Patients with RCC and bone
      metastasis received zoledronate and fluvastatin or atorvastatin. Patients were
      monitored clinically and by imaging for skeletal events. Concentrations of the
      bone resorption markers deoxypyridinoline (DPD) and N-telopeptide (NTX) and the
      bone formation marker bone-specific alkaline phosphatase (BSAP) were monitored
      for changes during treatment. RESULTS: Eleven patients were enrolled and followed
      for a median of 6 months. The median time to first skeletal-related event for all
      patients was 9.0 months. Seven (63%) patients experienced skeletal events with a
      median time to first skeletal-related event of 4.0 months (range, 3-18 months); 4
      patients (36%) experiences no skeletal events for a median of 12 months of follow
      up (range, 2-28 months); 4 patients (36%) demonstrated treatment responses with
      development of sclerosis in lytic bone lesions. Differences in the median changes
      in biomarker levels between patients who had skeletal events and those who did
      not were statistically significant for DPD and NTX (P = .03 and .01,
      respectively) but not for BSAP (P = .4). The regimen was well tolerated, with few
      adverse reactions related to the study drugs. CONCLUSION: Although the use of
      bone-targeting therapy combining zoledronate and fluvastatin or atorvastatin
      affected certain bone biomarkers and provided bone response in several patients
      with RCC and bone metastasis, we could not demonstrate a statistically
      significant improvement in time to skeletal events.

PMID- 21958524
TI  - Enzymatic synthesis of fatty acid ethyl esters by utilizing camellia oil
      soapstocks and diethyl carbonate.
AB  - This study was reported on a novel process for fatty acid ethyl esters
      preparation by transesterification and esterification from renewable low-cost
      feedstock camellia oil soapstocks and friendly acyl acceptor diethyl carbonate.
      The main components of product were 83.9% ethyl oleate, 8.9% ethyl palmitate,
      4.7% ethyl linoleate and 2.1% ethyl stearate, which could be used as eco-friendly
      renewable resources or additives of industrial solvent and fossil fuel. The
      effects of molar ratio of diethyl carbonate to soapstocks oil, lipases, organic
      solvent, reaction temperature and time were investigated, and process conditions
      were optimized. The yield was up to 98.4% in solvent-free system with molar ratio
      of diethyl carbonate to soapstocks oil 3:1 and 5% Novozym 435 (based on the
      weight of soapstocks oil) at 50  degrees C and 180 rpm for 24 h. Moreover, there
      was no obvious loss in the yield after lipases were reused for 10 batches without
      treatment under optimized conditions.

PMID- 21958525
TI  - Comparison of the carbon-sequestering abilities of pineapple leaf residue chars
      produced by controlled combustion and by field burning.
AB  - This study was undertaken to compare the chemical properties and yields of
      pineapple leaf residue (PLR) char produced by field burning (CF) with that
      produced by a partial combustion of air-dried PLR at 340  degrees C for 3 h in a
      furnace (CL). Higher total C, lignin content, and yield from CL as well as the
      presence of aromatic compounds in the Fourier Transform Infrared spectra of the
      char produced from CL suggest that the CL process was better in sequestering C
      than was the CF process. Although the C/N ratio of char produced from CL was low
      indicating a high N content of the char, the C in the char produced from CL was
      dominated by lignin suggesting that the decomposition of char produced from CL
      would be slow. To sequester C by char application, the PLR should be combusted in
      a controlled process rather than by burning in the field.

PMID- 21958526
TI  - Pretreatment of rice straw using an extrusion/extraction process at bench-scale
      for producing cellulosic ethanol.
AB  - A combination of a twin-screw extrusion and an acid-catalyzed hot water
      extraction process performed at a bench-scale was used to prepare high monomeric
      xylose hydrolysate for cellulosic production. The influences of the screw speed
      (30-150 rpm), barrel temperature (80-160  degrees C) and corresponding specific
      mechanical energy of the extruder on the structural properties of the pretreated
      rice straw, sugar concentration and conversion were investigated. The optimal
      condition for the extrusion step was determined to be 40 rpm with 3% H2SO4 at 120
      degrees C; the optimal condition for the extraction step was determined to be
      130  degrees C for 20 min. After the pretreatment at the optimal condition, 83.7%
      of the xylan was converted to monomeric xylose, and the concentration reached
      levels of 53.7 g/L. Finally, after the subsequent enzymatic hydrolysis, an 80%
      yield of the total saccharification was obtained.

PMID- 21958527
TI  - Tumor endothelial marker 7 (TEM-7): a novel target for antiangiogenic therapy.
AB  - Antiangiogenesis has been validated as a therapeutic strategy to treat cancer,
      however, a need remains to identify new targets and therapies for specific
      diseases and to improve clinical benefit from antiangiogenic agents. Tumor
      endothelial marker 7 (TEM-7) was investigated as a possible target for
      therapeutic antiangiogenic intervention in cancer. TEM-7 expression was assessed
      by in situ hybridization or by immunohistochemistry (IHC) in 130 formalin-fixed
      paraffin-embedded (FFPE) and 410 frozen human clinical specimens of cancer plus
      301 normal tissue samples. In vitro TEM-7 expression was evaluated in 4 human
      endothelial cell models and in 32 human cancer cell lines by RT-PCR and flow
      cytometry. An anti-TEM-7 antibody was tested in vitro on human SKOV3 ovarian and
      MDA-MB-231 breast carcinoma cells that expressed TEM-7 in antibody-dependent
      cellular cytotoxicity (ADCC) and phagocytosis assays. In frozen tumor tissues,
      TEM-7 mRNA and protein was detected in all but one of the cancer types tested and
      was infrequently expressed in normal frozen tissues. In FFPE tumor tissues, TEM-7
      protein was detected by IHC in colon, breast, lung, bladder, ovarian and
      endometrial cancers and in sarcomas. TEM-7 protein was not detected in head and
      neck, prostate or liver cancers. TEM-7 expression was restricted to the
      vasculature and was absent from tumor cells. In vitro, TEM-7 was not detected in
      human microvascular endothelial cells (HMVEC) or human umbilical vein endothelial
      cells (HUVEC) but was induced in endothelial precursor/progenitor cells (EPC) in
      the presence of the mitogen phorbol ester PMA. An anti-TEM-7 antibody mediated
      ADCC and phagocytosis in SKOV3 and MDA-MB-231 cell lines infected with an
      adenovirus expressing TEM-7. These data demonstrate that TEM-7 is a vascular
      protein associated with angiogenic states. TEM-7 is a novel and attractive target
      for antiangiogenic therapy.

PMID- 21958529
TI  - The hidden Chagas disease burden in Europe.

PMID- 21958528
TI  - Identification of class III beta-tubulin as a marker of angiogenic perivascular
      cells.
AB  - A full understanding of the functional role for pericytes in microvascular
      network growth requires identifying the specific cell phenotypes involved in
      angiogenesis. The objective of this study was to evaluate class III beta-tubulin
      expression along remodeling adult rat mesenteric microvascular networks.
      Mesenteric tissues were harvested from unstimulated adult male Wistar rats and at
      2, 10 and 30 days post-compound 48/80 stimulation (n=4 per experimental group).
      Tissues were immunohistochemically labeled with antibodies for class III beta
      tubulin, NG2 and PECAM. In unstimulated microvascular networks, class III beta
      tubulin was nerve specific, and did not identify vascular cells along PECAM
      positive arterioles, venules, and capillaries. Two days post 48/80 stimuli, class
      III beta-tubulin labeling of perivascular cells, including pericytes and smooth
      muscle cells, was observed along capillary sprouts, capillaries, venules, and
      arterioles in network regions characterized by increased vessel density and
      tortuosity. Pericyte identity along capillaries and capillary sprouts was
      confirmed by cell morphology and co-labeling with NG2. The percentage of vessels
      with class III beta-tubulin positive labeling decreased at subsequent time points
      and temporally correlated with the time course of capillary sprouting. The
      results identify class III beta-tubulin as a marker of angiogenic perivascular
      cells and suggest that specific pericyte phenotypes are associated with capillary
      sprouting.

PMID- 21958530
TI  - Clinical, electrocardiographic and echocardiographic abnormalities in Latin
      American migrants with newly diagnosed Chagas disease 2005-2009, Barcelona,
      Spain.
AB  - Following Latin American migration, Chagas disease has inevitably appeared in non
      endemic countries in Europe and elsewhere. New policies are necessary to prevent
      transmission in those countries but the long, often undetected chronic period of
      the early stages of the disease also renders epidemiological studies important.
      The main objective of our study was to determine the presence of clinical,
      electrocardiogram (ECG) and echocardiographic abnormalities in a population of
      Latin American migrants infected with Trypanosoma cruzi at the moment of
      diagnosis. We performed a hospital-based observational study of 100 adult
      patients with newly diagnosed Chagas infection between January 2005 and December
      2009. Thirty-seven patients were classified within the Brazilian Consensus on
      Chagas cardiomyopathy early cardiac stages (A or B1) and 49 presented
      pathological findings (stage B2) according to the Panamerican Health Organization
      Classification. Overall, 49 patients showed ECG and/or echocardiographic
      alterations. The presence of ECG and ecocardiographic alterations were
      significantly associated (p=0.038). The most frequent ECG and echocardiographic
      findings were right bundle branch block (12 cases) and impaired left ventricular
      wall relaxation (24 cases), respectively. In conclusion, ECG and
      echocardiographic alterations coherent with Chagas cardiomyopathy were found in a
      large proportion of newly diagnosed Latin American migrants infected with T.
      cruzi. In the mid-term, Chagas disease might become an important cause of chronic
      cadiomyopathy in our attendance area.

PMID- 21958531
TI  - Targeted screening and health education for Chagas disease tailored to at-risk
      migrants in Spain, 2007 to 2010.
AB  - Chagas disease is endemic in Latin America, but migration has expanded the
      disease's geographical limits. Spain is the most affected country in Europe. From
      2007, a specific Chagas disease programme aimed at at-risk migrants was developed
      in three Spanish cities (Madrid, Jerez de la Frontera and Alicante). The
      objectives of the programme were to increase participants' knowledge and decrease
      their fears about the disease and to encourage them to undergo screening for
      Trypanosoma cruzi infection. The programme was specially focused on migrants from
      Bolivia and Latin American women of childbearing age. Culturally tailored
      interventions were carried out in non-clinical settings. A total of 276 migrants
      were screened using a rapid immunochromatographic test following talks on the
      disease: the results were then later confirmed by standard serological tests. Of
      those tested, 44 (15.9%) were confirmed cases of Chagas disease. All of them came
      from Bolivia and a quarter were pregnant women. Of the 44 cases, 31 were later
      followed up at a specialised Chagas disease clinic. We consider that the
      adaptation of the programme to the target population's needs and collaboration
      with non-governmental organisations and migrants' associations contributed to the
      acceptance of the programme and the increasing number of patients seen at a
      specialised clinic.

PMID- 21958532
TI  - The current screening programme for congenital transmission of Chagas disease in
      Catalonia, Spain.
AB  - Due to considerable numbers of migrants from Chagas disease-endemic countries
      living in Catalonia, the Catalonian Health Department has recently implemented a
      screening programme for preventing congenital transmission, targeting Latin
      American pregnant women who attend antenatal consultations. Diagnosis of
      Trypanosoma cruzi infection in women is based on two positive serological tests.
      Screening of newborns from mothers with positive serology is based on a
      parasitological test during the first 48 hours of life and/or conventional
      serological analysis at the age of nine months. If either of these tests is
      positive, treatment with benznidazole is started following the World Health
      Organization's recommendations. The epidemiological surveillance of the programme
      is based on the Microbiological Reporting System of Catalonia, a well established
      network of laboratories. Once a positive case is reported, the responsible
      physician is asked to complete a structured epidemiological questionnaire.
      Clinical and demographic data are registered in the Voluntary Case Registry of
      Chagas Disease, a database administered by the Catalonian Health Department. It
      is expected that this programme will improve the understanding of the real burden
      of Chagas disease in the region. Furthermore, this initiative could encourage the
      implementation of similar programmes in other regions of Spain and even in other
      European countries.

PMID- 21958533
TI  - Surveillance of Chagas disease in pregnant women in Madrid, Spain, from 2008 to
      2010.
AB  - One of the most important modes of transmission of Trypanosoma cruzi infection in
      areas where it is not endemic is vertical transmission: from mother to child. The
      objective of this report is to assess the efficacy of different programmes of
      serological screening to monitor infection with T. cruzi in pregnant Latin
      American women living in Madrid (Spain). To achieve this, a retrospective study
      was undertaken from January 2008 to December 2010 in seven hospitals in the
      Autonomous Community of Madrid. Serological screening programmes were classified
      in two main strategies: a selective one (pregnant women from Bolivia) and a
      universal one (pregnant women from Latin America). A total of 3,839 pregnant
      women were tested and the overall prevalence was 3.96%. The rate of congenital
      transmission was 2.6%. The current monitoring programmes have variable coverage
      ranging between 26% (selective screening) and 100% (universal screening).
      Monitoring of pregnant women from Latin America only reaches full coverage if
      universal screening of pregnant women is carried out at any moment of pregnancy,
      including at delivery. A common national regulation is necessary in order to
      ensure homogenous implementation of screening.

PMID- 21958534
TI  - Central glucocorticoid receptor-mediated effects of the antidepressant,
      citalopram, in humans: a study using EEG and cognitive testing.
AB  - Our previous work in cellular and animal models has shown that antidepressants
      activate glucocorticoid receptor (GR) translocation, induce GR down-regulation,
      and decrease GR-mediated effects in the presence of GR agonists. However, whether
      these effects can be extrapolated to the human brain is still unclear. In this
      study, the effects of four days of treatment with the antidepressant, citalopram
      (20 mg/day), or placebo, were assessed in a double-blind, placebo-controlled,
      cross-over study. Central GR-mediated effects were examined by the effects of a
      single dose of cortisol (30 mg, orally) on two measures known to be sensitive to
      glucocorticoid administration: EEG alpha power and working memory function.
      Twenty healthy male subjects aged between 18 and 33 years participated to the
      study. The results suggest that GR activation by antidepressants, and the
      subsequent decrease in GR-mediated effects in the presence of GR agonists, indeed
      occurs in the human brain. Specifically, pre-treatment with citalopram decreased
      the well-known ability of cortisol to increase EEG alpha power and to impair
      working memory: cortisol-induced increase in EEG alpha power was (anteriorly) +15
      to +20% (p=0.01) after placebo and +5 to +8% (p>0.5) after citalopram; and
      cortisol-induced increase in working memory errors was (at level 12, on average)
      2.50 vs. 4.55 (p<0.05) after placebo and 4.10 vs. 3.35 (p>0.05) after citalopram.
      No effects were detected on alerting. These results are consistent with the
      notion that citalopram treatment activates GR translocation and inhibits the
      functional consequences of the subsequent cortisol administration. Our study
      further emphasizes the importance of the GR as a target for antidepressant action
      in humans.

PMID- 21958535
TI  - Defining the limits of radical cytoreductive surgery for ovarian cancer.
AB  - OBJECTIVE: Despite significant morbidity, surgical cytoreduction is the standard
      of care for ovarian cancer. We examined the outcomes of cytoreductive surgery to
      determine if there are groups of patients in which the morbidity is so
      substantial that alternate treatment strategies are warranted. METHODS: The
      Nationwide Inpatient Sample was used to identify women who underwent surgery for
      ovarian cancer from 1998 to 2007. The effect of age, number of radical procedures
      performed, and clinical characteristics on morbidity and mortality were examined.
      RESULTS: A total of 28,651 women were identified. The complication rates
      increased with age from 17.1% in those <50 years of age to 29.7% in women age 70
      79 and to 31.5% in those >= 80 (p<0.05). The number of extended procedures
      performed was also a predictor of morbidity; complications increased from 20.4%
      for women with 0 procedures to 34.0% for 1 and 44.0% for >= 2 procedures
      (p<0.0001). In multivariable analysis age, comorbidity, and the number of
      procedures performed were the strongest predictors of outcome. The morbidity
      associated with additional procedures was greatest in the elderly. Medical
      complications in women <50 years of age occurred in 10.2% of those who underwent
      0 radical procedures vs. 23.7% in those who underwent 2 or more procedures. For
      women >= 80 years, complications were noted in 18.3% for 0 procedures, and 33.3%
      for 2 or more procedures. CONCLUSION: The morbidity of cytoreduction is greatest
      in elderly women where the effects of age and the number of radical procedures
      performed have an additive effect on complication rates.

PMID- 21958536
TI  - Performance of a biosurfactant produced by a Bacillus subtilis strain isolated
      from crude oil samples as compared to commercial chemical surfactants.
AB  - In this work, the biosurfactant produced by a Bacillus subtilis strain isolated
      from crude oil samples was characterized and its properties compared with
      commercially available chemical surfactants. The purified biosurfactant
      production yield (Y(P/X)) was 0.20 g/gcell dry weight. The surface tension (29.0
      mN/m) and critical micelle concentration (40 mg/l) were found to be similar to
      the values previously reported for surfactin. Temperature and pH stability of the
      biosurfactant were also evaluated. The biosurfactant was exposed to different
      temperatures (20, 37 and 46 degrees C) during two weeks and was found to be as
      stable as the commercial chemical surfactants Glucopone((r))215,
      Glucopone((r))650, Findet((r))1214N/23 and linear alkylbenzene sulfonates (LAS).
      Moreover, the biosurfactant subjected to 121 degrees C for 20 min did not exhibit
      a significant loss of surface activity. Contrary to the commercial chemical
      surfactants that were found to be stable over a wide range of pH (3.0-10.0), the
      biosurfactant was unstable precipitating at pH values below 5.0. The
      emulsification indexes showed that the biosurfactant possesses equal or superior
      capacity to form emulsions with n-hexadecane as compared to the commercial
      chemical surfactants. Moreover, the anti-adhesive activity of the biosurfactant
      and commercial chemical surfactants was evaluated. The biosurfactant showed some
      activity against Staphylococcus aureus and Escherichia coli. Nevertheless, no
      particular trend or special effect could be assigned to the use of commercial
      chemical surfactants as anti-adhesives. Results gathered in this work suggest
      that the biosurfactant recovered from B. subtilis EG1 constitutes an interesting
      alternative to the commercial chemical surfactants with potential use in several
      industries.

PMID- 21958537
TI  - Gel formulations containing catanionic vesicles composed of alprenolol and SDS:
      effects of drug release and skin penetration on aggregate structure.
AB  - To fully utilize the extended contact time of gel formulations a novel
      formulation with drug containing catanionic aggregates offering prolonged drug
      release and skin penetration were investigated. This study aimed to further
      explore the drug release process from catanionic vesicles in gels. Catanionic
      vesicles were formed from alprenolol and sodium dodecyl sulphate. Physical gels
      composed of catanionic vesicles and a SoftCAT polymer were used as well as
      covalent Carbopol gels. Drug release was measured in vitro using a modified USP
      paddle method and the skin penetration was studied using dermatomized pig ear
      skin mounted in horizontal Ussing chambers. The aggregate structure was
      visualized with cryo-TEM during the drug release and skin penetration process.
      The study results show that catanionic vesicles are present in the formulations
      throughout the drug release process and during the clinically relevant skin
      application time. Hence, the decreased skin penetration rate stems from the
      prolonged release of drug substance from the gels. The rheological investigation
      shows that the gel structure of the physically cross-linked gels is maintained
      even as the drug substance is released and the gel volume is decreased. These
      findings indicate that the applicability of formulations like these is a future
      possibility.

PMID- 21958538
TI  - Synthesis of mesostructured polyaniline using mixed surfactants, anionic sodium
      dodecylsulfate and non-ionic polymers and their applications in H2O2 and glucose
      sensing.
AB  - Mesostructured polyaniline was prepared by the self-assembly of a mixture of an
      anionic surfactant, sodium dodecylsulfate and a non-ionic polymeric surfactant
      (polyethylene glycol, and block-co-polymers such as Pluronic P123 and Brij-35).
      Materials were characterized by a complementary combination of X-ray diffraction,
      Scanning electron microscopy, Fourier-transform infrared spectrometer and UV
      visible spectrophotometer. Mesostructured polyaniline was used for construction
      of biosensor, which displayed excellent electrocatalytic response for the
      detection of H(2)O(2) and glucose compared to conventional polyaniline. The
      electrocatalytic response observed in the case of mesostructured polyaniline can
      be correlated with the large surface area and nanopores which enhances the
      accessibility of H(2)O(2)/glucose molecule to the active site that result in high
      observed current. The methodology adopted in the present study provides a new
      platform for the fabrication of polyaniline based high-performance glucose and
      other biosensors.

PMID- 21958539
TI  - Effect of AOT-assisted multi-walled carbon nanotubes on antibacterial activity.
AB  - The dispersing power of surfactant-modified multiwalled carbon nanotubes (MWCNTs)
      and their effect on the antibacterial activity were examined. The MWCNTs were
      modified using a dioctyl sodium sulfosuccinate (AOT) surfactant. UV-vis
      spectroscopy and transmission electron microscopy (TEM) were used to characterize
      the dispersion of MWCNTs in the aqueous phase. Fourier transform infrared
      spectroscopy confirmed the results of UV-vis spectroscopy and TEM, indicating
      that the AOT molecules had been adsorbed successfully onto the MWCNT surface. The
      highly dispersed AOT-modified MWCNTs showed strong antibacterial activity to
      Streptococcus mutans. The fluorescence images showed that the AOT-modified MWCNTs
      were capable of capturing bacteria and forming cell aggregates as well as killing
      them. The optical density growth curves and colony-forming units assays confirmed
      that the antibacterial activity of the AOT-modified MWCNTs was concentration
      dependent and treatment time-dependent. This finding might be useful for
      applications of AOT-modified MWCNTs as an antibacterial agent to eliminate
      pathogens from a biocontaminated water phase.

PMID- 21958540
TI  - Discovery and optimization of a biphenylacetic acid series of prostaglandin D2
      receptor DP2 antagonists with efficacy in a murine model of allergic rhinitis.
AB  - Biphenylacetic acid (5) was identified through a library screen as an inhibitor
      of the prostaglandin D(2) receptor DP2 (CRTH2). Optimization for potency and
      pharmacokinetic properties led to a series of selective CRTH2 antagonists.
      Compounds demonstrated potency in a human DP2 binding assay and a human whole
      blood eosinophil shape change assay, as well as good oral bioavailability in rat
      and dog, and efficacy in a mouse model of allergic rhinitis following oral
      dosing.

PMID- 21958541
TI  - Synthesis and anti-inflammatory activity of some new 4,5-dihydro-1,5-diaryl-1H
      pyrazole-3-substituted-heteroazole derivatives.
AB  - A series of 4,5-dihydro-1,5-diaryl-1H-pyrazole-3-substituted-heteroazoles were
      designed and synthesized in order to obtain new compounds with potential anti
      inflammatory activity. The title compounds were screened for in vivo anti
      inflammatory activity by using Carrageenan induced rat paw edema method.
      Diclofenac sodium was used as a standard drug for comparison. Out of the 30
      compounds tested, compound 19a, 19b, 25a, 25b exhibited significant anti
      inflammatory activity. Selected compounds were also screened for in vitro COX-2
      inhibition assay and analgesic activity in the acetic acid induced writhing
      model.

PMID- 21958542
TI  - Synthesis and evaluation of cytotoxic effects of hanultarin and its derivatives.
AB  - One of the known cytotoxic lignans is (-)-1-O-feruloyl-secoisolariciresinol
      designated as hanultarin, which was isolated from the seeds of Trichosanthes
      kirilowii. In this Letter, we described the first synthesis of 1-O-feruloyl
      secoisolariciresinol, 1,4-O-diferuloyl-secoisolariceresinol and their analogues.
      The cytotoxicities of these compounds were evaluated against several cancer cell
      lines. Interestingly, we found that the feruloyl diester derivative of
      secoisolariciresinol was the most active cytotoxic compound against all the
      cancer cells tested in this experiment. The IC(50) values of the1,4-O-diferuloyl
      secoisolariceresinol were in the range of 7.1-9.8MUM except one cell line. In
      considering that both ferulic acid and secoisolariciresinol are commonly found in
      many plants and have no cytotoxicity, this finding is remarkable in that simple
      covalent bonds between the ferulic acid and secoisolariciresinol cause a
      cytotoxic effect.

PMID- 21958543
TI  - Synthesis, stereochemistry and in vitro antimicrobial evaluation of novel 2-[(2,4
      diaryl-3-azabicyclo[3.3.1]nonan-9-ylidene)hydrazono]-4-phenyl-2,3
      dihydrothiazoles.
AB  - 2-[(2,4-Diaryl-3-azabicyclo[3.3.1]nonan-9-ylidene)hydrazono]-4-phenyl-2,3
      dihydrothiazoles (3a-3k) have been synthesized by the cyclization of 2-[(2,4
      diaryl-3-azabicyclo[3.3.1]nonan-9-one thiosemicarbazones with phenacyl bromide
      and characterized by analytical (melting point and elemental analysis) and
      spectral (IR, (1)H NMR, (13)C NMR, D(2)O exchange, NOESY and mass) techniques.
      The novel Hantzsch products (3a-3k) were screened for their in vitro
      antibacterial and antifungal activities against some selected microorganisms.
      Structure activity relationship (SAR) for the reported compounds was studied by
      comparing their MIC values with standard drugs (Streptomycin and Amphotericin B).
      The results show that 3e against Escherichia coli and Cryptococcus neoformans3i
      against Bacillus Subtilis, 3b against Aspergillus flavus, and 3k against Rhizopus
      sp. were found to show significant growth inhibition.

PMID- 21958544
TI  - Indolin-2-one p38alpha inhibitors III: bioisosteric amide replacement.
AB  - Crystallographic structural information was used in the design and synthesis of a
      number of bioisosteric derivatives to replace the amide moiety in a lead series
      of p38alpha inhibitors which showed general hydrolytic instability in human liver
      preparations. Triazole derivative 13 was found to have moderate bioavailability
      in the rat and demonstrated potent in-vivo activity in an acute model of
      inflammation.

PMID- 21958545
TI  - 2-Oxo-N-aryl-1,2,3,4-tetrahydroquinoline-6-sulfonamides as activators of the
      tumor cell specific M2 isoform of pyruvate kinase.
AB  - Compared to normal differentiated cells, cancer cells have altered metabolic
      regulation to support biosynthesis and the expression of the M2 isozyme of
      pyruvate kinase (PKM2) plays an important role in this anabolic metabolism. While
      the M1 isoform is a highly active enzyme, the alternatively spliced M2 variant is
      considerably less active and expressed in tumors. While the exact mechanism by
      which decreased pyruvate kinase activity contributes to anabolic metabolism
      remains unclear, it is hypothesized that activation of PKM2 to levels seen with
      PKM1 may promote a metabolic program that is not conducive to cell proliferation.
      Here we report the third chemotype in a series of PKM2 activators based on the 2
      oxo-N-aryl-1,2,3,4-tetrahydroquinoline-6-sulfonamide scaffold. The synthesis,
      structure activity relationships, selectivity and notable physiochemical
      properties are described.

PMID- 21958546
TI  - Discovery of 1-arylcarbonyl-6,7-dimethoxyisoquinoline derivatives as glutamine
      fructose-6-phosphate amidotransferase (GFAT) inhibitors.
AB  - Through high throughput screening and subsequent hit identification and
      optimization, we synthesized a series of 1-arylcarbonyl-6,7-dimethoxyisoquinoline
      derivatives as the first reported potent and reversible GFAT inhibitors. SAR
      studies of this class of compounds indicated significant impact on GFAT
      inhibition potency by substitutions on the A-ring and C-ring. The ketone group
      was found to be necessary for high potency. Compound 28 (RO0509347) demonstrated
      potent GFAT inhibition (IC(50)=1MUM) with a desirable pharmacokinetic profile in
      rats, and showed significant efficacy in reducing the glucose excursion in an
      OGTT test in ob/ob mice.

PMID- 21958547
TI  - Imidazo[1,5-a]quinoxalines as irreversible BTK inhibitors for the treatment of
      rheumatoid arthritis.
AB  - Imidazo[1,5-a]quinoxalines were synthesized that function as irreversible
      Bruton's tyrosine kinase (BTK) inhibitors. The syntheses and SAR of this series
      of compounds are presented as well as the X-ray crystal structure of the lead
      compound 36 in complex with a gate-keeper variant of ITK enzyme. The lead
      compound showed good in vivo efficacy in preclinical RA models.

PMID- 21958548
TI  - Oxygen-dependent regulation of nitric oxide production by inducible nitric oxide
      synthase.
AB  - Inducible nitric oxide synthase (iNOS) catalyzes the reaction that converts the
      substrates O(2) and l-arginine to the products nitric oxide (NO) and l
      citrulline. Macrophages, and many other cell types, upregulate and express iNOS
      primarily in response to inflammatory stimuli. Physiological and
      pathophysiological oxygen tension can regulate NO production by iNOS at multiple
      levels, including transcriptional, translational, posttranslational, enzyme
      dimerization, cofactor availability, and substrate dependence. Cell culture
      techniques that emphasize control of cellular PO(2), and measurement of NO or its
      stable products, have been used by several investigators for in vitro study of
      the O(2) dependence of NO production at one or more of these levels. In most cell
      types, prior or concurrent exposure to cytokines or other inflammatory stimuli is
      required for the upregulation of iNOS mRNA and protein by hypoxia. Important
      transcription factors that target the iNOS promoter in hypoxia include hypoxia
      inducible factor 1 and/or nuclear factor kappaB. In contrast to the upregulation
      of iNOS by hypoxia, in most cell types NO production is reduced by hypoxia.
      Recent work suggests a prominent role for O(2) substrate dependence in the short
      term regulation of iNOS-mediated NO production.

PMID- 21958549
TI  - Extracorporeal membrane oxygenation as a bridge to liver transplantation for
      acute respiratory distress syndrome-induced life-threatening hypoxaemia
      aggravated by hepatopulmonary syndrome.
AB  - INTRODUCTION: Combined with massive lung aeration loss resulting from acute
      respiratory distress syndrome, hepatopulmonary syndrome, a liver-induced vascular
      lung disorder characterized by diffuse or localized dilated pulmonary
      capillaries, may induce hypoxaemia and death in patients with end-stage liver
      disease. METHODS: The case of such a patient presenting with both disorders and
      in whom an extracorporeal membrane oxygenation was used is described. RESULTS: A
      51-year-old man with a five-year history of alcoholic cirrhosis was admitted for
      acute respiratory failure, platypnoea and severe hypoxaemia requiring emergency
      tracheal intubation. Following mechanical ventilation, hypoxaemia remained
      refractory to positive end-expiratory pressure, 100% of inspired oxygen and
      inhaled nitric oxide. Two-dimensional contrast-enhanced (agitated saline)
      transthoracic echocardiography disclosed a massive right-to-left extracardiac
      shunt, without patent foramen ovale. Contrast computed tomography (CT) of the
      thorax using quantitative analysis and colour encoding system established the
      diagnosis of acute respiratory distress syndrome aggravated by hepatopulmonary
      syndrome. According to the severity of the respiratory condition, a veno-venous
      extracorporeal membrane oxygenation was implemented and the patient was listed
      for emergency liver transplantation. Orthotopic liver transplantation was
      performed at Day 13. At the end of the surgical procedure, the improvement in
      oxygenation allowed removal of extracorporeal membrane oxygenation (Day 5). The
      patient was discharged from hospital at Day 48. Three months after hospital
      discharge, the patient recovered a correct physical autonomy status without
      supplemental O2. CONCLUSIONS: In a cirrhotic patient, acute respiratory distress
      syndrome was aggravated by hepatopulmonary syndrome causing life-threatening
      hypoxaemia not controlled by standard supportive measures. The use of
      extracorporeal membrane oxygenation, by controlling gas exchange, allowed the
      performing of a successful liver transplantation and final recovery.

PMID- 21958550
TI  - Theorizing the health service usage behavior of family caregivers: a qualitative
      study of an internet-based intervention.
AB  - PURPOSE: The purpose of this qualitative study was to improve understanding of
      family caregivers' use of Web-based intervention support by integrating three
      theoretical models. The study applied the Anderson's model of health service
      utilization, Venkatesh's theory of technology acceptance, and Chatman's and
      Wilson's information behavior theories. METHODS: This qualitative study is part
      of a larger study. An interpretive grounded theory approach was used to conduct
      in-depth interviews with Chinese caregivers of family members with dementia. The
      caregivers received Internet-based information support and personalized e-mail
      intervention. A purposive sample of fourteen caregivers was selected to
      participate in the interviews. Constant comparison, analytic memoing, case
      analysis, and concept mapping were used to conduct theoretical triangulation
      analysis. RESULTS: Three main factors influenced the use of the intervention: (a)
      caregiver needs, which are influenced by personal capacity, social support
      available, and caregiving belief; (b) information communication technology (ICT)
      factors, including accessibility barriers and perceived efforts to use the
      technology; and (c) style of using the technology, such as preference for using e
      mail or the customized Website. The personal capacity of caregivers was
      influenced by many factors, including computer and language proficiency, health
      service knowledge, caregiving competence and competing roles and
      responsibilities. Social support available for caregivers included available
      computer, language or caregiving support and health service knowledge. Caregiving
      belief included traditional belief of giving care, and health belief of the
      illness. New caregivers needed a different kind of support intervention compared
      with experienced caregivers. Caregivers with different amounts of experience
      tended to have different learning styles, with new caregivers preferring
      interactive intervention and more experienced caregivers preferring more
      reflective learning. CONCLUSIONS: This study reinforced the findings of the
      larger quantitative study that it is important to address both care-giving needs
      and technology factors in Internet-based intervention. The quantitative study
      found that less competent caregivers with more positive attitudes towards
      technology tended to use the intervention more frequently. In this qualitative
      research, the findings revealed that caregiver needs, ICT factors, and style of
      use explained the pattern of intervention use. This new conceptualization has
      integrated information acceptance, health service utilization, and information
      behavior theories. More studies will be needed to confirm if the proposed concept
      can explain or predict the usage behavior in other Web-based interventions.

PMID- 21958551
TI  - Engagement in "My Child's Asthma", an interactive web-based pediatric asthma
      management intervention.
AB  - PURPOSE: The Internet is a promising tool for delivering health behavior change
      programs although such interventions raise questions about participant engagement
      in this medium. In this study we sought to determine the characteristics of
      parents who engage in an Internet-based health intervention for their children
      (with asthma) and to distinguish parents who engage at the prescribed intervals
      versus those who engage less often. METHODS: N=283 parents with children who had
      asthma were recruited and randomized to receive a web-based intervention.
      Participants filled out six surveys over a 6-month period asking them about
      demographic and clinical characteristics, outcome expectations and self-efficacy
      beliefs regarding asthma control for their child, and attitudes about computers
      and the Internet. Descriptive statistics were used to describe the population and
      analyze associations. RESULTS: Controller use and being adherent to this
      medication as well as positive outcome and self efficacy expectations were
      associated with increased engagement. Parents who logged on only once reported
      significantly less frequent use of the Internet than parents who logged on to all
      sessions. DISCUSSION AND CONCLUSION: The results of this study suggest that it is
      important to find ways to increase engagement in a web-based intervention for
      parents who are not yet engaging in the recommended behaviors and/or who report
      less positive outcome and efficacy expectations around asthma management.

PMID- 21958552
TI  - Chemoimmunotherapy in acute lymphoblastic leukemia.
AB  - ALL blast cells express a variety of specific antigens e.g. CD19, CD20, CD22,
      CD33, and CD52, which serve as targets for Monoclonal Antibodies (MoAbs). So far,
      the most experience is available for anti-CD20 (rituximab), which has been
      combined with chemotherapy for treatment of mature B-ALL/Burkitt's lymphoma.
      Studies with rituximab have also been completed in B-precursor ALL. Another
      antigen, CD19, is of great interest due to a very high rate of expression in ALL.
      It can be targeted by a bispecific monoclonal antibody, Blinatumomab, directed
      against CD19 and CD3. Smaller studies or case reports are also available for the
      anti CD52 antibody (Alemtuzumab), for anti CD22 (Epratuzumab) or anti CD33
      (Gemtuzumab). Available data demonstrate that MoAb therapy in ALL is a highly
      promising targeted treatment. However, several details for an optimal treatment
      approach e.g. the required level of antigen expression, timing, schedule, dosage
      and stage of disease still need to be defined.

PMID- 21958553
TI  - Decreased concentrations of soluble interleukin-1 receptor accessory protein
      levels in the peritoneal fluid of women with endometriosis.
AB  - Interleukin 1 (IL1) may play an important role in endometriosis-associated pelvic
      inflammation, and natural specific inhibitors, including soluble IL1 receptor
      accessory protein (sIL1RAcP) and soluble IL1 receptor type 2 (sIL1R2), are
      critical for counterbalancing the pleiotropic effects of IL1. The objective of
      this study was to evaluate the levels of sIL1RAcP, together with those of sIL1R2
      and IL1beta, in the peritoneal fluid of women with and without endometriosis.
      Peritoneal fluid samples were obtained at laparoscopy and assessed by ELISA.
      sIL1RAcP concentrations were reduced in endometriosis stages I-II and III-IV.
      sIL1R2 concentrations were decreased, and those of IL1beta were significantly
      increased in endometriosis stages I-II. sIL1RAcP and sIL1R2 concentrations were
      significantly decreased in the secretory phase of the menstrual cycle, and
      IL1beta concentrations were elevated in the proliferative and the secretory
      phases. sIL1RAcP and sIL1R2 concentrations were reduced in women with
      endometriosis who were infertile, fertile, suffering from pelvic pain or pain
      free. However, IL1beta concentrations were significantly reduced in women with
      endometriosis who were infertile or had pelvic pain. These changes may exacerbate
      the local peritoneal inflammatory reaction observed in women with endometriosis
      and contribute to endometriosis pathophysiology and the major symptoms of this
      disease.

PMID- 21958554
TI  - Receptor fusion proteins for the inhibition of cytokines.
AB  - Cells are exposed to a large variety of cytokines that signal through
      corresponding cytokine receptors. In healthy tissues or tissues that respond
      properly to disturbed homeostasis, the cross-talk of a few conserved core
      signaling pathways downstream of the cytokine receptors is translated into an
      adequate cellular response. In chronic inflammatory diseases but also in cancer
      associated inflammation cytokine expression and the downstream signaling networks
      are dysregulated. Targeted therapies are aimed at the specific interference with
      dysregulated cytokine signaling. In this article some concepts of pharmacological
      intervention with cytokine signaling will be reviewed including biologics that
      target cytokines and cytokine receptors. Receptor fusion proteins consisting of
      the ligand-binding domains of cytokine receptors are highly specific and potent
      cytokine inhibitors and will be discussed in more detail.

PMID- 21958555
TI  - Effects of temperature on the transmission of Yersinia Pestis by the flea,
      Xenopsylla Cheopis, in the late phase period.
AB  - BACKGROUND: Traditionally, efficient flea-borne transmission of Yersinia pestis,
      the causative agent of plague, was thought to be dependent on a process referred
      to as blockage in which biofilm-mediated growth of the bacteria physically blocks
      the flea gut, leading to the regurgitation of contaminated blood into the host.
      This process was previously shown to be temperature-regulated, with blockage
      failing at temperatures approaching 30 degrees C; however, the abilities of fleas
      to transmit infections at different temperatures had not been adequately
      assessed. We infected colony-reared fleas of Xenopsylla cheopis with a wild type
      strain of Y. pestis and maintained them at 10, 23, 27, or 30 degrees C. Naive
      mice were exposed to groups of infected fleas beginning on day 7 post-infection
      (p.i.), and every 3-4 days thereafter until day 14 p.i. for fleas held at 10
      degrees C, or 28 days p.i. for fleas held at 23-30 degrees C. Transmission was
      confirmed using Y. pestis-specific antigen or antibody detection assays on mouse
      tissues. RESULTS: Although no statistically significant differences in per flea
      transmission efficiencies were detected between 23 and 30 degrees C, efficiencies
      were highest for fleas maintained at 23 degrees C and they began to decline at 27
      and 30 degrees C by day 21 p.i. These declines coincided with declining median
      bacterial loads in fleas at 27 and 30 degrees C. Survival and feeding rates of
      fleas also varied by temperature to suggest fleas at 27 and 30 degrees C would be
      less likely to sustain transmission than fleas maintained at 23 degrees C. Fleas
      held at 10 degrees C transmitted Y. pestis infections, although flea survival was
      significantly reduced compared to that of uninfected fleas at this temperature.
      Median bacterial loads were significantly higher at 10 degrees C than at the
      other temperatures. CONCLUSIONS: Our results suggest that temperature does not
      significantly effect the per flea efficiency of Y. pestis transmission by X.
      cheopis, but that temperature is likely to influence the dynamics of Y. pestis
      flea-borne transmission, perhaps by affecting persistence of the bacteria in the
      flea gut or by influencing flea survival. Whether Y. pestis biofilm production is
      important for transmission at different temperatures remains unresolved, although
      our results support the hypothesis that blockage is not necessary for efficient
      transmission.

PMID- 21958557
TI  - Alpha-mangostin, a polyphenolic xanthone derivative from mangosteen, attenuates
      beta-amyloid oligomers-induced neurotoxicity by inhibiting amyloid aggregation.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized
      by the accumulation of beta-sheet-rich amyloid oligomers or fibrils which are
      associated with cellular toxicity in the brain. Inhibition of Abeta aggregation
      could be a viable therapeutic strategy for slowing and/or preventing the progress
      of AD. Here we reported that alpha-mangostin (alpha-M), a polyphenolic xanthone
      derivative from mangosteen, concentration-dependently attenuated the
      neurotoxicity induced by Abeta-(1-40) or Abeta-(1-42) oligomers (EC(50) = 3.89
      nM, 4.14 nM respectively) as observed by decreased cell viability and impaired
      neurite outgrowth in primary rat cerebral cortical neurons. Molecular docking and
      dynamics simulations demonstrated that alpha-M could potentially bind to Abeta
      and stabilize alpha-helical conformation. alpha-M was found to directly
      dissociate Abeta-(1-40) and Abeta-(1-42) oligomers by blotting with oligomer
      specific antibodies. ThioflavinT fluorescence assay and electron microscopy
      imaging further demonstrated that alpha-M blocked the fibril formation as well as
      disturbed the pre-formed fibrils. Taken together, our results indicate that alpha
      M is capable to inhibit and dissociate the Abeta aggregation, which could
      contribute to its effect of attenuating Abeta oligomers-induced neurotoxicity.
      Thus, alpha-M could be a great potential candidate for AD treatment. This article
      is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.

PMID- 21958556
TI  - What implementation interventions increase cancer screening rates? a systematic
      review.
AB  - BACKGROUND: Appropriate screening may reduce the mortality and morbidity of
      colorectal, breast, and cervical cancers. However, effective implementation
      strategies are warranted if the full benefits of screening are to be realized. As
      part of a larger agenda to create an implementation guideline, we conducted a
      systematic review to evaluate interventions designed to increase the rate of
      breast, cervical, and colorectal cancer (CRC) screening. The interventions
      considered were: client reminders, client incentives, mass media, small media,
      group education, one-on-one education, reduction in structural barriers,
      reduction in out-of-pocket costs, provider assessment and feedback interventions,
      and provider incentives. Our primary outcome, screening completion, was
      calculated as the overall median post-intervention absolute percentage point (PP)
      change in completed screening tests. METHODS: Our first step was to conduct an
      iterative scoping review in the research area. This yielded three relevant high
      quality systematic reviews. Serving as our evidentiary foundation, we conducted a
      formal update. Randomized controlled trials and cluster randomized controlled
      trials, published between 2004 and 2010, were searched in MEDLINE, EMBASE and
      PSYCHinfo. RESULTS: The update yielded 66 studies new eligible studies with 74
      comparisons. The new studies ranged considerably in quality. Client reminders,
      small media, and provider audit and feedback appear to be effective interventions
      to increase the uptake of screening for three cancers. One-on-one education and
      reduction of structural barriers also appears effective, but their roles with CRC
      and cervical screening, respectively, are less established. More study is
      required to assess client incentives, mass media, group education, reduction of
      out-of-pocket costs, and provider incentive interventions. CONCLUSION: The new
      evidence generally aligns with the evidence and conclusions from the original
      systematic reviews. This review served as the evidentiary foundation for an
      implementation guideline. Poor reporting, lack of precision and consistency in
      defining operational elements, and insufficient consideration of context and
      differences among populations are areas for additional research.

PMID- 21958558
TI  - miR-181 targets multiple Bcl-2 family members and influences apoptosis and
      mitochondrial function in astrocytes.
AB  - Mitochondria are central to the execution of apoptosis, and the Bcl-2 protein
      family of pro- and anti-apoptotic proteins interacts with mitochondria to
      regulate apoptosis. Using bioinformatics we predicted that miR-181, a microRNA
      expressed in brain, could target the 3'UTRs of Bcl-2 family members Bcl-2
      L11/Bim, Mcl-1, and Bcl-2. Using the luciferase reporter assay we confirmed these
      targets. We used mimic and inhibitor to alter miR-181a levels in primary
      astrocyte cultures and found miR-181a reduction was associated with increased Bcl
      2 and Mcl-1 protein levels. Decreased miR-181a levels reduced glucose deprivation
      induced apoptosis, mitochondrial dysfunction, and loss of mitochondrial membrane
      potential in astrocytes.

PMID- 21958559
TI  - Noise, air pollutants and traffic: continuous measurement and correlation at a
      high-traffic location in New York City.
AB  - BACKGROUND: Epidemiological studies have linked both noise and air pollution to
      common adverse health outcomes such as increased blood pressure and myocardial
      infarction. In urban settings, noise and air pollution share important sources,
      notably traffic, and several recent studies have shown spatial correlations
      between noise and air pollution. The temporal association between these
      exposures, however, has yet to be thoroughly investigated despite the importance
      of time series studies in air pollution epidemiology and the potential that
      correlations between these exposures could at least partly confound statistical
      associations identified in these studies. METHODS: An aethelometer, for
      continuous elemental carbon measurement, was co-located with a continuous noise
      monitor near a major urban highway in New York City for six days in August 2009.
      Hourly elemental carbon measurements and hourly data on overall noise levels and
      low, medium and high frequency noise levels were collected. Hourly average
      concentrations of fine particles and nitrogen oxides, wind speed and direction
      and car, truck and bus traffic were obtained from nearby regulatory monitors.
      Overall temporal patterns, as well as day-night and weekday-weekend patterns,
      were characterized and compared for all variables. RESULTS: Noise levels were
      correlated with car, truck, and bus traffic and with air pollutants. We observed
      strong day-night and weekday-weekend variation in noise and air pollutants and
      correlations between pollutants varied by noise frequency. Medium and high
      frequency noise were generally more strongly correlated with traffic and traffic
      related pollutants than low frequency noise and the correlation with medium and
      high frequency noise was generally stronger at night. Correlations with nighttime
      high frequency noise were particularly high for car traffic (Spearman rho=0.84),
      nitric oxide (0.73) and nitrogen dioxide (0.83). Wind speed and direction
      mediated relationships between pollutants and noise. CONCLUSIONS: Noise levels
      are temporally correlated with traffic and combustion pollutants and correlations
      are modified by the time of day, noise frequency and wind. Our results underscore
      the potential importance of assessing temporal variation in co-exposures to noise
      and air pollution in studies of the health effects of these urban pollutants.

PMID- 21958561
TI  - A meta-analysis of the outcome of endovascular and noninvasive therapies in the
      treatment of intermittent claudication.
AB  - PURPOSE: Intermittent claudication is a common symptom of peripheral arterial
      disease. Currently, there is a lack of consensus on the most effective therapies
      for this problem. We conducted a meta-analysis of randomized trials assessing the
      efficacy of endovascular therapy (EVT) compared with noninvasive therapies for
      the treatment of intermittent claudication. METHODS: Randomized trials comparing
      the efficacy of EVT and noninvasive therapies, such as medical therapy (MT) and
      supervised exercise (SVE) in patients with intermittent claudication were
      identified by a systematic search. Data were pooled, and combined overall effect
      sizes (standardized differences of mean values) were calculated for a random
      effect model in terms of ankle-brachial index (ABI) and treadmill walking for
      initial claudication distance (ICD) and maximum walking distance (MWD). Nine
      eligible trials (873 participants) were included: two compared EVT and MT alone,
      four compared EVT and SVE, and three trials compared EVT plus SVE vs SVE alone.
      RESULTS: Heterogeneity between studies was marked. Quantitative data analysis
      suggested that EVT improved outcomes over MT alone at early follow-up
      evaluations. Outcomes of EVT plus SVE were better than those of SVE alone in
      terms of both ABI and treadmill walking at immediate, early, and intermediate
      follow-up. No substantial differences in outcomes of EVT alone compared with SVE
      alone were found. CONCLUSION: In patients with intermittent claudication, current
      evidence supports improved ABI and treadmill walking when EVT is added to MT or
      SVE during early and intermediate follow-up. There is no evidence that EVT alone
      provides improved outcome over SVE alone. There is low confidence in these
      findings for a number of reasons, including the small number of trials, the small
      size of these studies, the heterogeneity in study design, and the limited use of
      quality of life tools in assessing outcomes. More consistent data from larger,
      more homogenous studies, including longer follow-up, are required.

PMID- 21958560
TI  - 2011 ACCF/AHA focused update of the guideline for the management of patients with
      peripheral artery disease (updating the 2005 guideline): a report of the American
      College of Cardiology Foundation/American Heart Association Task Force on
      Practice Guidelines: developed in collaboration with the Society for
      Cardiovascular Angiography and Interventions, Society of Interventional
      Radiology, Society for Vascular Medicine, and Society for Vascular Surgery.

PMID- 21958562
TI  - Use of a remotely steerable "robotic" catheter in a branched endovascular aortic
      graft.
AB  - We report the use of a remotely steerable catheter to treat kinked renal bridging
      stents 8 months after branched endovascular repair of a type III thoracoabdominal
      aortic aneurysm. Conventional techniques using single, coaxial, and manually
      steerable sheaths proved too unstable to provide the support required to pass a
      wire against resistance through the kinked stent. A remotely steerable "robotic"
      catheter provided sufficient precision and stability to cross the kink and reline
      it with an additional stent, restoring renal perfusion. This technology can help
      achieve precise and stable introducer sheath position. Further evaluation is
      necessary to understand the wider applications.

PMID- 21958563
TI  - Initial experience with a new fenestrated stent graft.
AB  - OBJECTIVES: The Anaconda fenestrated stent graft (Vascutek, Inchinnan, United
      Kingdom) is a new device that can easily be repositioned during deployment. This
      study evaluated its feasibility for treating abdominal aortic aneurysms with
      inadequate infrarenal sealing zones. METHODS: Patients undergoing stent graft
      placement at two institutions in the United Kingdom were recruited. RESULTS: A
      total of 12 visceral vessels were accommodated with 8 fenestrations for renal
      arteries and 4 superior mesenteric artery valleys/scallops in 4 patients. One
      type Ib endoleak was identified at the 1-month follow-up and successfully
      treated. CONCLUSIONS: The Anaconda fenestrated stent graft device can be used for
      the repair of abdominal aortic aneurysms with hostile anatomy and has acceptable
      immediate and short-term results.

PMID- 21958564
TI  - Compression syndromes of the popliteal neurovascular bundle due to Baker cyst.
AB  - BACKGROUND: The purpose of this study was to perform a comprehensive search of
      the literature for all studies, case reports, and series describing Baker cyst
      compression of the neurovascular bundle in the popliteal fossa and index their
      findings according to the structures compressed. METHOD: Case reports and series
      obtained after a thorough MEDLINE search were indexed according to compressed
      structures. Patient demographics, main findings, method of diagnosis, cyst size,
      outcomes, and follow-up were recorded for each publication. RESULTS: Signs and
      symptoms related to popliteal vein and tibial nerve compression were the most
      frequent presentation of symptomatic Baker cysts, due to the anatomic
      vulnerability of these structures within the popliteal fossa and their relative
      sensitivity to compression. Patients with tibial nerve entrapment demonstrated
      gastrocnemius muscle atrophy, paresthesias, and pain. Those with popliteal vein
      compression experienced swelling, pain, and rarely, venous thromboembolism.
      Isolated arterial compression, presenting with intermittent claudication, is a
      rare occurrence because it is a relatively stiff-walled vessel, has a higher
      pressure, and is located deep in the popliteal fossa. Combinations of these
      compression syndromes are most frequently encountered in the context of cyst
      rupture and resulting compartment syndrome. CONCLUSIONS: Baker cyst is an
      important pathology for the differential diagnosis of popliteal neurovascular
      compression phenomena. It has a wide spectrum of presentation, therefore
      requiring accurate diagnosis for proper patient management. Because Baker cyst is
      by definition a chronic disorder, long-term follow-up is necessary to monitor
      patient recovery and prevent recurrence.

PMID- 21958565
TI  - Covered stent use after subclavian artery and vein injuries in the setting of
      vascular Ehlers-Danlos.
AB  - Vascular Ehlers-Danlos (VED) represents a rare disorder in which a defect in
      collagen synthesis renders vessels to be extremely fragile. We report the
      successful repair of a subclavian artery pseudoaneurysm via a hybrid technique
      employing delivery of a covered stent along with video-assisted thoracoscopic
      ligation of the internal mammary artery in a patient with VED.

PMID- 21958566
TI  - Diagnosis and treatment of venous lymphedema.
AB  - BACKGROUND: Chronic venous disease (CVD) is a common cause of secondary
      lymphedema. Venous lymphedema is sometimes misdiagnosed as primary lymphedema and
      does not receive optimal treatment. We have routinely used intravascular
      ultrasound (IVUS) imaging in all cases of limb swelling. The aim of this study is
      to show that (1) routine use of IVUS can detect venous obstruction missed by
      traditional venous testing, and (2) iliac-caval venous stenting can yield
      satisfactory clinical relief and can sometimes reverse abnormal lymphangiographic
      findings. METHODS: The study comprised CVD patients who underwent iliac vein
      stenting. Lymphangiography was abnormal in 72 of 443 CEAP C(3) limbs, with leg
      swelling as the primary complaint (abnormal lymphangiography group). Clinical
      features and stent outcome were compared with a control group of 205 of 443 with
      normal lymphangiography (normal lymphangiographic group). RESULTS: Clinical
      features were a poor guide to the diagnosis of lymphedema. Isotope
      lymphangiography was not helpful in differentiating primary from secondary
      lymphedema. Venography had 61% sensitivity to the diagnosis of venous
      obstruction. IVUS had a sensitivity of 88% for significant (>=50% area stenosis)
      venous obstruction. At 40 months, cumulative secondary stent patency was similar
      for the abnormal (100%) and normal lymphangiographic (95%) groups. Swelling
      improved significantly after stent placement in the abnormal lymphangiographic
      group (mean [standard deviation] swelling grade improvement 0.8 +/- 1.1) but was
      less (P < .004) than in the control group (1.4 +/- 1.3). Complete swelling relief
      was 16% and 44% (P < .001) and partial improvement (>=1 grade of swelling) was
      45% and 66% (P < .01) in the abnormal and normal lymphangiographic groups,
      respectively. Associated pain was present in 50% and 36% of the swollen limbs in
      the abnormal and normal lymphangiographic groups. Pain relief (>=3 visual analog
      scale) at 40 months was 87% and 83%, respectively (P = .3), with 65% and 71%,
      experiencing complete pain relief. Quality of life criteria improved after stent
      placement in both groups but to a better extent in the normal lymphangiographic
      group. Abnormal lymphangiography improved or normalized in 9 of 36 (25%) of those
      tested after stent correction. CONCLUSIONS: Prevailing practice patterns and
      diagnostic deficiencies probably result in the misdiagnosis of many cases of
      venous lymphedema as "primary" lymphedema. IVUS is recommended to rule out venous
      obstruction as the associated or initiating cause of lymphedema. Iliac venous
      stenting to correct the obstruction has excellent long-term patency and good
      clinical outcome, although results are not as good as in those with normal
      lymphatic function.

PMID- 21958567
TI  - Endovascular management of ruptured infected popliteal artery aneurysm.
AB  - Infected popliteal aneurysm is a rare high-risk condition that can present as an
      emergency with acute rupture and sepsis. Management of acute ischemia in the
      presence of local and systemic sepsis is challenging. Open surgery is not always
      possible and carries a high risk of morbidity and death. An endovascular approach
      has been advocated in infected aneurysms elsewhere in the body, with good short
      term and medium-term outcomes encouraging such approach in the popliteal artery.
      We report a case of successful endovascular treatment of an infected ruptured
      popliteal aneurysm with favorable outcome after 2-year follow-up and a related
      review of the literature.

PMID- 21958568
TI  - Case of the disappearing heat-induced thrombus causing pulmonary embolism during
      ultrasound evaluation.
AB  - We report a case of a 58-year-old male patient who underwent successful
      endovenous radiofrequency ablation of the left great saphenous vein for CEAP
      class 4a venous disease. On the third postoperative day, he had a duplex
      ultrasound scan for evaluation which showed successful occlusion of the great
      saphenous vein (GSV) with class 2 endovenous heat-induced thrombus (EHIT) that
      disappeared during the evaluation and caused a pulmonary embolism. To our
      knowledge, no case of pulmonary embolism has been reported to occur during
      postoperative follow-up duplex scanning. Relevant literature is reviewed and a
      possible mechanism for thrombus dislodgement is entertained.

PMID- 21958569
TI  - Two cases of tracheoinnominate artery fistula following tracheostomy treated
      successfully by endovascular embolization of the innominate artery.
AB  - Tracheoinnominate artery fistula (TIF) is a rare but lethal complication of
      tracheostomy. Treatment has traditionally been surgical, but advances in
      endovascular technology have led to a few recent reports of therapy with coils.
      We report 2 cases of TIF with massive hemorrhage that underwent successful
      treatment with endovascular occlusion. Endovascular repair is less invasive than
      open surgical repair and usually associated with a shorter recovery period.
      However, this technique may require multiple coils to inhibit blood flow into the
      fistula. This procedure should be considered one of the useful treatments for
      TIF.

PMID- 21958570
TI  - Endovascular management of acute aortic dissections.
AB  - INTRODUCTION: Acute aortic dissection (AAD) is one of the most common aortic
      emergencies that vascular specialists are asked to manage. Traditional surgical
      interventions for cases complicated by malperfusion have resulted in significant
      morbidity and mortality. With increasing availability of thoracic endografts,
      endovascular interventions for complicated AAD have become more acceptable. We
      reviewed our experience with endovascular treatment of AAD since January 2005.
      METHODS: Medical records of patients admitted for AAD from January 1, 2005, to
      December 31, 2008, were entered into our vascular registry and analyzed for risk
      factors, extent of dissection, type of management, fate of the false lumen,
      complications, and survival. There were 249 admissions for aortic dissections
      during the study period. Our study group included 28 patients with complicated
      AAD who underwent endovascular intervention. RESULTS: During the study interval,
      28 patients (16 male) underwent 44 procedures. The average age was 54 years. Risk
      factors differed from the typical atherosclerotic patient and were dominated by
      an 89.3% incidence of hypertension. Five patients (17.9%) presented with a
      history of recent cocaine use. The average length of stay was 25.1 days (range, 1
      196 days). Stanford type B dissections were present in all but one patient.
      Twenty-six thoracic endografts were placed in 25 patients. Eight patients
      required multiple procedures in addition to a thoracic endograft. Morbidity
      occurred in 17 (60.7%) patients, with renal insufficiency occurring in 11
      patients (39.3%) and one requiring permanent dialysis. Four neurologic events
      occurred: three strokes (10.7%) and one patient (3.6%) with temporary paraplegia.
      Three patients (10.7%) died in the periprocedural period, with ruptured
      dissection in one and pericardial tamponade in another. Eight of 10 computed
      tomography scans (80%) available for review in follow-up showed complete
      thrombosis of the thoracic false lumen. CONCLUSIONS: Complicated AAD remains a
      challenging problem, with significant morbidity and mortality rates. However, our
      early experience with endovascular management offers a favorable reduction in
      mortality from historic controls.

PMID- 21958571
TI  - Innovation for polio eradication.

PMID- 21958572
TI  - Time to get serious about HIV antiretroviral resistance.

PMID- 21958574
TI  - Treatment of hospital-acquired pneumonia.

PMID- 21958575
TI  - Treatment of hospital-acquired pneumonia.

PMID- 21958576
TI  - Treatment of hospital-acquired pneumonia.

PMID- 21958577
TI  - Treatment of hospital-acquired pneumonia.

PMID- 21958578
TI  - Treatment of hospital-acquired pneumonia.

PMID- 21958580
TI  - Escherichia coli O104:H4 south-west France, June 2011.

PMID- 21958581
TI  - Insights into human antifungal immunity from primary immunodeficiencies.
AB  - Some mendelian (monogenic) disorders directly conferring increased susceptibility
      are associated with diverse infectious organisms, whereas others are restricted
      in scope to specific genera or even to one species. So far, most investigations
      of primary immunodeficiency disorders have focused on those conferring
      susceptibility to viral, bacterial, or mycobacterial infections, providing
      powerful insight into human determinants of host resistance to these microbes.
      Monogenic disorders that increase susceptibility to fungal infections are
      increasingly being recognised. Although infections associated with these
      disorders are probably less common than are iatrogenic associated mycoses, they
      provide valuable insight into human immunity to fungal infections. Investigation
      of these immunological pathways will ultimately lead to improvements in
      management of such infections in secondarily immunocompromised patients.

PMID- 21958582
TI  - Determinants of mortality in naval units during the 1918-19 influenza pandemic.
AB  - In 1918, two waves of epidemic influenza arose with very different clinical
      phenotypes. During the first wave, infection rates were high but mortality was
      low. During the second wave, high numbers of deaths occurred and mortality
      differed 30-100 times among seemingly similar groups of affected adults, but the
      reason for this variation is unclear. In 1918, the crews of most warships and
      some island populations were affected by influenza during both waves of infection
      and had no or very few deaths during the second wave. However, some warships and
      island populations were not affected during the first wave of infection and had
      high mortality during the second wave. These findings suggest that infection
      during the first wave protected against death, but not infection, during the
      second wave. If so, the two waves of infection were probably caused by
      antigenically distinct influenza viruses--not by one virus that suddenly
      increased in pathogenicity between the first and second waves. These findings are
      relevant to modern concerns that the 2009 influenza A H1N1 virus could suddenly
      increase in lethality.

PMID- 21958583
TI  - Acrodermatitis chronica atrophicans.

PMID- 21958584
TI  - Rituximab successfully treats refractory chronic autoimmune urticaria caused by
      IgE receptor autoantibodies.

PMID- 21958585
TI  - Mepolizumab, a humanized anti-IL-5 mAb, as a treatment option for severe nasal
      polyposis.
AB  - BACKGROUND: Approximately 85% of nasal polyps (NPs) in white subjects are
      characterized by prominent eosinophilia. IL-5 is the key driver of eosinophilic
      differentiation and survival. OBJECTIVE: We sought to investigate the therapeutic
      potential of inhibiting IL-5 with a humanized mAb as treatment for severe nasal
      polyposis. METHODS: Thirty patients with severe nasal polyposis (grade 3 or 4 or
      recurrent after surgery) refractory to corticosteroid therapy were randomized in
      a double-blind fashion to receive either 2 single intravenous injections (28 days
      apart) of 750 mg of mepolizumab (n = 20) or placebo (n = 10). Change from
      baseline in NP score was assessed monthly until 1 month after the last dose (week
      8). Computed tomographic scans were also performed at week 8. RESULTS: Twelve of
      20 patients receiving mepolizumab had a significantly improved NP score and
      computed tomographic scan score compared with 1 of 10 patients receiving placebo
      at week 8 versus baseline. CONCLUSION: Mepolizumab achieved a statistically
      significant reduction in NP size for at least 1 month after dosing in 12 of 20
      patients. IL-5 inhibition is a potential novel therapeutic approach in patients
      with severe eosinophilic nasal polyposis.

PMID- 21958586
TI  - Anaphylaxis in an allergy immunotherapy extract-compounding technician after an
      extract needle stick.

PMID- 21958587
TI  - Maternal obesity during pregnancy as a risk for early-life asthma.

PMID- 21958588
TI  - Marijuana use among traumatic event-exposed adolescents: posttraumatic stress
      symptom frequency predicts coping motivations for use.
AB  - Contemporary comorbidity theory postulates that people suffering from
      posttraumatic stress symptoms may use substances to cope with negative affect
      generally and posttraumatic stress symptoms specifically. The present study
      involves the examination of the unique relation between past two-week
      posttraumatic stress symptom frequency and motives for marijuana use after
      accounting for general levels of negative affectivity as well as variability
      associated with gender. Participants were 61 marijuana-using adolescents
      (M(age)=15.81) who reported experiencing lifetime exposure to at least one
      traumatic event. Consistent with predictions, past two-week posttraumatic stress
      symptoms significantly predicted coping motives for marijuana use and were not
      associated with social, enhancement, or conformity motives for use. These
      findings are consistent with theoretical work suggesting people suffering from
      posttraumatic stress use substances to regulate symptoms.

PMID- 21958589
TI  - The sorption behavior of DDT onto sediment in the presence of surfactant
      cetyltrimethylammonium bromide.
AB  - The sorption behavior of p,p'- and o,p'-dichlorodiphenyltrichloroethane (DDT) in
      the presence of a cationic surfactant cetyltrimethylammonium bromide (CTAB) on
      sediment was studied. Batch experiments were carried out to investigate the
      kinetics and thermodynamics of the process. The kinetic behavior of these three
      chemicals on sediment was described by pseudo-second-order kinetic equations, and
      the isotherms followed the Freundlich model well. The presence of CTAB was able
      to remarkably accelerate and enhance the sorption of DDT, whereas DDT showed no
      effect on the sorption of CTAB in our considered concentration ranges. The
      thermodynamic parameters, such as standard enthalpy change (DeltaH0), standard
      entropy change (DeltaS0) and standard Gibbs free energy change (DeltaG0) showed
      that the sorption process of p,p'- and o,p'-DDT was physical, spontaneous and
      exothermic, and the randomness at the solid-liquid interface increased during the
      process. In the presence of CTAB, the sorption of DDT showed significantly
      negative DeltaG0 and DeltaH0 values.

PMID- 21958590
TI  - The one new journal we might actually need.

PMID- 21958591
TI  - Muscle glycogen storage disease 0 presenting recurrent syncope with weakness and
      myalgia.
AB  - Muscle glycogen storage disease 0 (GSD0) is caused by glycogen depletion in
      skeletal and cardiac muscles due to deficiency of glycogen synthase 1 (GYS1),
      which is encoded by the GYS1 gene. Only two families with this disease have been
      identified. We report a new muscle GSD0 patient, a Japanese girl, who had been
      suffering from recurrent attacks of exertional syncope accompanied by muscle
      weakness and pain since age 5 years until she died of cardiac arrest at age 12.
      Muscle biopsy at age 11 years showed glycogen depletion in all muscle fibers. Her
      loss of consciousness was gradual and lasted for hours, suggesting that the
      syncope may not be simply caused by cardiac event but probably also contributed
      by metabolic distress.

PMID- 21958593
TI  - Imaging synaptic plasticity.
AB  - Over the past decade, the use and development of optical imaging techniques has
      advanced our understanding of synaptic plasticity by offering the spatial and
      temporal resolution necessary to examine long-term changes at individual
      synapses. Here, we review the use of these techniques in recent studies of
      synaptic plasticity and, in particular, long-term potentiation in the
      hippocampus.

PMID- 21958594
TI  - Effects of short-term food deprivation on interoceptive awareness, feelings and
      autonomic cardiac activity.
AB  - The perception of internal bodily signals (interoception) plays a relevant role
      for emotion processing and feelings. This study investigated changes of
      interoceptive awareness and cardiac autonomic activity induced by short-term food
      deprivation and its relationship to hunger and affective experience. 20 healthy
      women were exposed to 24h of food deprivation in a controlled setting.
      Interoceptive awareness was assessed by using a heartbeat tracking task. Felt
      hunger, cardiac autonomic activity, mood and subjective appraisal of
      interoceptive sensations were assessed before and after fasting. Results show
      that short-term fasting intensifies interoceptive awareness, not restricted to
      food cues, via changes of autonomic cardiac and/or cardiodynamic activity. The
      increase of interoceptive awareness was positively related to felt hunger.
      Additionally, the results demonstrate the role of cardiac vagal activity as a
      potential index of emotion related self-regulation, for hunger, mood and the
      affective appraisal of interoceptive signals during acute fasting.

PMID- 21958595
TI  - The holistic processing of price comparison: behavioral and electrophysiological
      evidences.
AB  - Although considerable studies have investigated the cognitive mechanism and the
      neural basis of number processing, it is unclear how numbers are represented in
      the practical context such as price comparison. In the present study,
      participants were asked to judge whether the target prices with different units
      (yuan, jiao, fen) were "higher or lower than 5 jiao" while event-related
      potentials were recorded. The behavioral results did not reveal a main effect of
      distance when distance was defined in terms of the digits of prices. However, a
      significant effect of distance was found when distance was defined in terms of
      the whole magnitude of prices. The electrophysiological results revealed similar
      distance effects (DE) during the 350-450 ms interval after stimulus onset, with
      an enhanced positivity for far distance than for close distance. These findings
      suggest that the digits and the units of prices are processed holistically rather
      than separately during a price comparison task.

PMID- 21958596
TI  - Cold acclimation in the moss Physcomitrella patens involves abscisic acid
      dependent signaling.
AB  - Overwintering plants develop tolerance to freezing stress through a cold
      acclimation process by which the cells provoke internal protective mechanisms
      against freezing. The stress hormone abscisic acid (ABA) is known to increase
      freezing tolerance of plant cells, but its role in cold acclimation has not been
      determined. In this study, we used ABA-insensitive lines of the moss
      Physcomitrella patens to determine whether cold acclimation in bryophytes
      involves an ABA-dependent process. Two ABA-insensitive lines, both impaired in
      ABA signaling without showing ABA-induced stress tolerance, were subjected to
      cold acclimation, and changes in freezing tolerance and accumulation of soluble
      sugars and proteins were compared to the wild type. The wild-type cells acquired
      freezing tolerance in response to cold acclimation treatment, but very little
      increase in freezing tolerance was observed in the ABA-insensitive lines.
      Analysis of low-molecular-weight soluble sugars indicated that the ABA
      insensitive lines accumulated sucrose, a major compatible solute in bryophytes,
      to levels comparable with those of the wild type during cold acclimation.
      However, accumulation of the trisaccharide theanderose and of specific LEA-like
      boiling-soluble proteins was very limited in the ABA-insensitive lines.
      Furthermore, analysis of cold-induced expression of genes encoding LEA-like
      proteins revealed that the ABA-insensitive lines accumulate only small amounts of
      these transcripts during cold acclimation. Our results indicate that cold
      acclimation of bryophytes requires an ABA-dependent signaling process. The
      results also suggest that cold-induced sugar accumulation, depending on the sugar
      species, can either be dependent or independent of the ABA-signaling pathway.

PMID- 21958597
TI  - Employment of patients receiving maintenance dialysis and after kidney
      transplant: a cross-sectional study from Finland.
AB  - BACKGROUND: Associations between mode of renal replacement therapy and employment
      rate have not been well characterized. STUDY DESIGN: Cross-sectional registry
      analysis. SETTING & PARTICIPANTS: The employment status of all prevalent 15- to
      64-year-old dialysis and kidney transplant patients in Finland at the end of 2007
      (N = 2,637) was analyzed by combining data from the Finnish Registry for Kidney
      Diseases with individual-level employment statistics of the Finnish government.
      PREDICTOR: Prevalence rate ratios (PRRs) of employment according to treatment
      modality with adjustment for age, sex, cause of end-stage renal disease (ESRD),
      duration of ESRD, and comorbid conditions were estimated using Cox regression
      with a constant time at risk. OUTCOME: Employment status of patients on dialysis
      therapy or after transplant. MEASUREMENTS: Clinical data were collected from the
      Finnish Registry for Kidney Diseases, and employment data were acquired from
      Statistics Finland. RESULTS: 19% of hemodialysis patients, 31% of peritoneal
      dialysis patients, and 40% of patients with a functioning transplant were
      employed; the overall employment rate for the Finnish population aged 15-64 years
      is 67%. Home hemodialysis patients and those treated with automated peritoneal
      dialysis had employment rates of 39% and 44%, respectively. In adjusted analysis,
      patients on home hemodialysis therapy (PRR, 1.87), on automated peritoneal
      dialysis therapy (PRR, 2.14), or with a kidney transplant (PRR, 2.30) had higher
      probabilities of employment than in-center hemodialysis patients. Patients with
      type 1 or 2 diabetes as the cause of ESRD had the lowest probability of
      employment (PRR, 0.48-0.60 compared with glomerulonephritis). Patients aged 25-54
      years more frequently were employed than those younger than 25 or older than 54
      years. Sex did not predict employment. For transplant recipients, longer time
      since transplant was associated with higher employment in addition to the
      mentioned factors. LIMITATIONS: Cross-sectional design. CONCLUSIONS: Employment
      rate of home dialysis patients was similar to that of transplant recipients and
      higher than that of in-center hemodialysis patients. Patients with diabetes were
      less likely to be employed.

PMID- 21958592
TI  - Empirical derivation of the reference region for computing diagnostic sensitive
      18fluorodeoxyglucose ratios in Alzheimer's disease based on the ADNI sample.
AB  - Careful selection of the reference region for non-quantitative positron emission
      tomography (PET) analyses is critically important for Region of Interest (ROI)
      data analyses. We introduce an empirical method of deriving the most suitable
      reference region for computing neurodegeneration sensitive (18)fluorodeoxyglucose
      (FDG) PET ratios based on the dataset collected by the Alzheimer's Disease
      Neuroimaging Initiative (ADNI) study. Candidate reference regions are selected
      based on a heat map of the difference in coefficients of variation (COVs) of FDG
      ratios over time for each of the Automatic Anatomical Labeling (AAL) atlas
      regions normalized by all other AAL regions. Visual inspection of the heat map
      suggests that the portion of the cerebellum and vermis superior to the horizontal
      fissure is the most sensitive reference region. Analyses of FDG ratio data show
      increases in significance on the order of ten-fold when using the superior
      portion of the cerebellum as compared with the traditionally used full
      cerebellum. The approach to reference region selection in this paper can be
      generalized to other radiopharmaceuticals and radioligands as well as to other
      disorders where brain changes over time are hypothesized and longitudinal data is
      available. Based on the empirical evidence presented in this study, we
      demonstrate the usefulness of the COV heat map method and conclude that intensity
      normalization based on the superior portion of the cerebellum may be most
      sensitive to measuring change when performing longitudinal analyses of FDG-PET
      ratios as well as group comparisons in Alzheimer's disease. This article is part
      of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.

PMID- 21958599
TI  - Contrast enhanced liver MRI in patients with primary sclerosing cholangitis:
      inverse appearance of focal confluent fibrosis on delayed phase MR images with
      hepatocyte specific versus extracellular gadolinium based contrast agents.
AB  - RATIONALE AND OBJECTIVES: To assess the enhancement pattern of focal confluent
      fibrosis (FCF) on contrast-enhanced hepatic magnetic resonance imaging (MRI)
      using hepatocyte-specific (Gd-EOB-DTPA) and extracellular (ECA) gadolinium-based
      contrast agents in patients with primary sclerosing cholangitis (PSC). MATERIALS
      AND METHODS: After institutional review board approval, 10 patients with PSC (6
      male, 4 female; 33-61 years) with 13 FCF were included in this retrospective
      study. All patients had a Gd-EOB-DTPA-enhanced liver MRI exam, and a comparison
      ECA-enhanced MRI. On each T1-weighted dynamic dataset, the signal intensity (SI)
      of FCF and the surrounding liver as well as the paraspinal muscle (M) were
      measured. In the Gd-EOB-DTPA group, hepatocyte phase images were also included.
      SI FCF/SI M, SI liver/SI M, and [(SI liver - SI FCF)/SI liver] were compared
      between the different contrast agents for each dynamic phase using the paired
      Student's t-test. RESULTS: There was no significant difference in SI FCF/SI M in
      all imaging phases. SI liver/SI M was significantly higher for the Gd-EOB-DTPA
      group in the delayed phase (P < .001), whereas there was no significant
      difference in all other imaging phases. In the Gd-EOB-DTPA group, mean [(SI liver
      - SI FCF)/SI liver] were as follows (values for ECA group in parentheses):
      unenhanced phase: 0.26 (0.26); arterial phase: 0.01 (-0.31); portal venous phase
      (PVP): -0.05 (-0.26); delayed phase (DP): 0.14 (-0.54); and hepatocyte phase:
      0.26. Differences were significant for the DP (P < .001). CONCLUSIONS: On delayed
      phase MR images the FCF-to-liver contrast is reversed with the lesions appearing
      hyperintense on ECA enhanced images and hypointense on Gd-EOB-DTPA-enhanced
      images.

PMID- 21958600
TI  - Diffraction enhanced imaging of a rat model of gastric acid aspiration
      pneumonitis.
AB  - RATIONALE AND OBJECTIVES: Diffraction-enhanced imaging (DEI) is a type of phase
      contrast x-ray imaging that has improved image contrast at a lower dose than
      conventional radiography for many imaging applications, but no studies have been
      done to determine if DEI might be useful for diagnosing lung injury. The goals of
      this study were to determine if DEI could differentiate between healthy and
      injured lungs for a rat model of gastric aspiration and to compare diffraction
      enhanced images with chest radiographs. MATERIALS AND METHODS: Radiographs and
      diffraction-enhanced chest images of adult Sprague Dawley rats were obtained
      before and 4 hours after the aspiration of 0.4 mL/kg of 0.1 mol/L hydrochloric
      acid. Lung damage was confirmed with histopathology. RESULTS: The radiographs and
      diffraction-enhanced peak images revealed regions of atelectasis in the injured
      rat lung. The diffraction-enhanced peak images revealed the full extent of the
      lung with improved clarity relative to the chest radiographs, especially in the
      portion of the lower lobe that extended behind the diaphragm on the
      anteroposterior projection. CONCLUSIONS: For a rat model of gastric acid
      aspiration, DEI is capable of distinguishing between a healthy and an injured
      lung and more clearly than radiography reveals the full extent of the lung and
      the lung damage.

PMID- 21958598
TI  - Biogenesis and assembly of eukaryotic cytochrome c oxidase catalytic core.
AB  - Eukaryotic cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial
      respiratory chain. COX is a multimeric enzyme formed by subunits of dual genetic
      origin which assembly is intricate and highly regulated. The COX catalytic core
      is formed by three mitochondrial DNA encoded subunits, Cox1, Cox2 and Cox3,
      conserved in the bacterial enzyme. Their biogenesis requires the action of
      messenger-specific and subunit-specific factors which facilitate the synthesis,
      membrane insertion, maturation or assembly of the core subunits. The study of
      yeast strains and human cell lines from patients carrying mutations in structural
      subunits and COX assembly factors has been invaluable to identify these ancillary
      factors. Here we review the current state of knowledge of the biogenesis and
      assembly of the eukaryotic COX catalytic core and discuss the degree of
      conservation of the players and mechanisms operating from yeast to human. This
      article is part of a Special Issue entitled: Biogenesis/Assembly of Respiratory
      Enzyme Complexes.

PMID- 21958601
TI  - A margin sharpness measurement for the diagnosis of breast cancer from magnetic
      resonance imaging examinations.
AB  - RATIONALE AND OBJECTIVES: Cancer screening by magnetic resonance imaging (MRI)
      has been shown to be one of the most sensitive methods available for the early
      detection of breast cancer. There is high variability in the diagnostic accuracy
      of radiologists analyzing the large amounts of data acquired in a breast MRI
      examination, and this has motivated substantial research toward the development
      of computer-aided detection and diagnosis systems. Most computer-aided diagnosis
      systems for breast MRI focus on dynamic information (how a lesion's brightness
      changes over the course of an examination after the injection of a contrast
      agent). The inclusion of lesion margin measurements is much less common. One
      characteristic of malignant tumors is that they grow into neighboring tissues.
      This growth creates tumor margins that are variably fuzzy or diffuse (ie, they
      are not sharp). MATERIALS AND METHODS: In this short report, the authors present
      a new method for measuring a tumor's margin from breast MRI examinations and
      compare it with an existing mathematical technique for margin measurements.
      RESULTS: The proposed method can yield a test with sensitivity of 77%
      (specificity, 65%) on screening data, outperforming existing mathematical lesion
      margin measurement methods. Furthermore, when the presented margin measurement is
      combined with existing dynamic features, there is a statistically significant
      improvement in computer-aided diagnosis test performance (P < .0014).
      CONCLUSIONS: The proposed method for measuring a tumor's margin outperforms
      existing mathematical methods on an extremely challenging data set containing
      many small lesions. The technique presented may be useful in discriminating
      between malignant and benign lesions in the context of the computer-aided
      diagnosis of breast cancer from MRI.

PMID- 21958603
TI  - The Systemic Lupus Erythematosus Responder Index (SRI); a new SLE disease
      activity assessment.
AB  - Systemic Lupus Erythematosus (SLE), because of its complex and multisystemic
      presentation, lacks a reliable and sensitive gold standard for measuring disease
      activity. In addition, there is no standardized method for defining response to
      therapy. Several disease activity indices have been developed over the years,
      each with their own positive and negative aspects. Growing insight in the
      pathogenesis of inflammatory diseases like SLE leads to the introduction of
      specific targeted biologic therapies. To investigate the efficacy of these new
      biologic agents, disease activity must be monitored regularly by a reliable and
      validated instrument. Recent studies on new biologics for treatment of SLE use a
      new composite measurement for disease activity and response in SLE. This new
      disease activity assessment, called SLE Responder Index (SRI), comprises criteria
      from three different internationally validated indices, SELENA-SLE Disease
      Activity Index (SELENA-SLEDAI), Physician Global Assessment (PGA) and the British
      Isles Lupus Assessment Group (BILAG) 2004. This review gives an overview of
      current available disease activity indices in relation to the newly developed
      composite SRI.

PMID- 21958602
TI  - Effective interventions to facilitate the uptake of breast, cervical and
      colorectal cancer screening: an implementation guideline.
AB  - BACKGROUND: Appropriate screening may reduce the mortality and morbidity of
      colorectal, breast, and cervical cancers. Several high-quality systematic reviews
      and practice guidelines exist to inform the most effective screening options.
      However, effective implementation strategies are warranted if the full benefits
      of screening are to be realized. We developed an implementation guideline to
      answer the question: What interventions have been shown to increase the uptake of
      cancer screening by individuals, specifically for breast, cervical, and
      colorectal cancers? METHODS: A guideline panel was established as part of Cancer
      Care Ontario's Program in Evidence-based Care, and a systematic review of the
      published literature was conducted. It yielded three foundational systematic
      reviews and an existing guidance document. We conducted updates of these reviews
      and searched the literature published between 2004 and 2010. A draft guideline
      was written that went through two rounds of review. Revisions were made resulting
      in a final set of guideline recommendations. RESULTS: Sixty-six new studies
      reflecting 74 comparisons met eligibility criteria. They were generally of poor
      to moderate quality. Using these and the foundational documents, the panel
      developed a draft guideline. The draft report was well received in the two rounds
      of review with mean quality scores above four (on a five-point scale) for each of
      the items. For most of the interventions considered, there was insufficient
      evidence to support or refute their effectiveness. However, client reminders,
      reduction of structural barriers, and provision of provider assessment and
      feedback were recommended interventions to increase screening for at least two of
      three cancer sites studied. The final guidelines also provide advice on how the
      recommendations can be used and future areas for research. CONCLUSION: Using
      established guideline development methodologies and the AGREE II as our
      methodological frameworks, we developed an implementation guideline to advise on
      interventions to increase the rate of breast, cervical and colorectal cancer
      screening. While advancements have been made in these areas of implementation
      science, more investigations are warranted.

PMID- 21958605
TI  - [Greetings].

PMID- 21958606
TI  - [Focus on diagnostic studies].

PMID- 21958604
TI  - Malondialdehyde-acetaldehyde-adducted protein inhalation causes lung injury.
AB  - In addition to cigarette smoking, alcohol exposure is also associated with
      increased lung infections and decreased mucociliary clearance. However, little
      research has been conducted on the combination effects of alcohol and cigarette
      smoke on lungs. Previously, we have demonstrated in a mouse model that the
      combination of cigarette smoke and alcohol exposure results in the formation of a
      very stable hybrid malondialdehyde-acetaldehyde (MAA)-adducted protein in the
      lung. In in vitro studies, MAA-adducted protein stimulates bronchial epithelial
      cell interleukin-8 (IL-8) via the activation of protein kinase C epsilon (PKCE).
      We hypothesized that direct MAA-adducted protein exposure in the lungs would
      mimic such a combination of smoke and alcohol exposure leading to airway
      inflammation. To test this hypothesis, C57BL/6J female mice were intranasally
      instilled with either saline, 30MUL of 50MUg/mL bovine serum albumin (BSA)-MAA,
      or unadducted BSA for up to 3 weeks. Likewise, human lung surfactant proteins A
      and D (SPA and SPD) were purified from human pulmonary proteinosis lung lavage
      fluid and successfully MAA-adducted in vitro. Similar to BSA-MAA, SPD-MAA was
      instilled into mouse lungs. Lungs were necropsied and assayed for histopathology,
      PKCE activation, and lung lavage chemokines. In control mice instilled with
      saline, normal lungs had few inflammatory cells. No significant effects were
      observed in unadducted BSA- or SPD-instilled mice. However, when mice were
      instilled with BSA-MAA or SPD-MAA for 3 weeks, a significant peribronchiolar
      localization of inflammatory cells was observed. Both BSA-MAA and SPD-MAA
      stimulated increased lung lavage neutrophils and caused a significant elevation
      in the chemokine, keratinocyte chemokine, which is a functional homologue to
      human IL-8. Likewise, MAA-adducted protein stimulated the activation of airway
      and lung slice PKCE. These data support that the MAA-adducted protein induces a
      proinflammatory response in the lungs and that the lung surfactant protein is a
      biologically relevant target for malondialdehyde and acetaldehyde adduction.
      These data further implicate MAA-adduct formation as a potential mechanism for
      smoke- and alcohol-induced lung injury.

PMID- 21958607
TI  - Applicability of diagnostic studies--statistics, bias and estimates of diagnostic
      accuracy.
AB  - Reviewing and using diagnostic research for decision making involves complex
      issues about what are the exact diagnostic questions, how they should be studied,
      and to whom the results of such studies apply in real life. In this paper we aim
      to address some of the main issues concerning applicability of diagnostic
      research by looking at different diagnostic questions, what different study
      designs can be used and how bias and variability may impact on applicability.
      Users of diagnostic research should be aware of these issues in order to avoid
      confusion and misunderstandings about why modern diagnostic research addresses
      particular patient groups and uses certain study designs, whilst choosing to
      ignore others that at first glance seem relevant. We conclude that there are 4
      main points to be addressed in doing and using diagnostic research, and these
      are: "Get the question right"; "Get the study design right"; "Include patients
      for whom the test will also be used in practice"; and "Educate users of
      research". Simple as they may seem, these points cover extremely complex issues
      in practice, and these need to be addressed by more communication between
      methodologists, practitioners and decision makers.

PMID- 21958609
TI  - [The benefit of diagnostic tests--from surrogate endpoints to patient-relevant
      endpoints].
AB  - The patient-relevant benefit of diagnostic tests should be evaluated; addressing
      diagnostic accuracy alone is not sufficient, though. Several phased evaluation
      schemes for diagnostic tests have been proposed in the literature. They all have
      in common that studies evaluating the effect on patient outcome have a central
      position. Various designs are available to evaluate the effect of a diagnostic
      test on patient outcome. Five design options are presented and their pros and
      cons discussed. Indeed, such studies are feasible. Under exceptional conditions,
      however, it may be sufficient to base evaluation on diagnostic accuracy studies
      combined with further information (mostly from treatment trials).

PMID- 21958611
TI  - [Reliability of molecular tumour markers in children with medulloblastoma--an
      example from clinical practice].
AB  - During the 1960s less than five percent of the children suffering from cancer
      could be cured. Today we are able to cure approximately three quarters. It is
      research in molecular biology elucidating the origin of cancer at the level of
      cells, genes and molecules that has accounted for this success. Research results
      include, for example, the identification of molecular markers of leukaemia that
      are able to predict the intensity of therapy necessary for maximum benefit.
      Furthermore, molecular markers have been identified for paediatric brain tumours
      which raise the hope for more individualized and targeted therapy.

PMID- 21958613
TI  - [Patient stratification: interactions between diagnosis and therapy].
AB  - There is a high interest in developing diagnostic tests, e.g. in terms of
      molecular markers. Usually diagnostic tests are judged by their accuracy. The
      benefit of diagnostic testing for the patient, though, can only derive from the
      received treatment after diagnosis. In this way, interaction between diagnostic
      testing and therapy is a prerequisite. In such cases diagnostic testing is
      predictive of therapy. To show its interaction, diagnostic tests should be
      embedded in randomised controlled trials.

PMID- 21958615
TI  - [What should physicians know about diagnostic testing?].
AB  - Many diagnostic tests ordered by physicians cannot be justified by rational
      criteria. However, this is not necessarily a problem of knowledge or lack
      thereof. The rational use of diagnostic tests must also be understood as a
      behavioural problem. Apart from knowledge, financial incentives, tradition and
      patient expectations have an impact on diagnostic decisions, too. Traditional
      academic teaching with its emphasis on pathophysiology prevents medical students
      from adopting a critical attitude to diagnostic testing. Against the background
      of cognitive psychology research on adaptive behaviour, I would suggest to
      increase clinical exposure in the undergraduate curriculum. This should be
      accompanied by a "reflective practicum" to improve the understanding of the
      usefulness of diagnostic tests in a particular situation. Working environments
      should be examined as to the feedback they provide for clinicians. Remuneration
      and utilization patterns may be more important determinants of test-ordering than
      a clinicians' knowledge. Nevertheless, a basic understanding of Bayes' theorem
      and likelihood ratios are an essential part of the medical curriculum.

PMID- 21958617
TI  - ["The right to know": are patients having mandatory health insurance in Germany
      entitled to receive diagnostic services that have no medical consequences?].
AB  - Patients have the right to know whether they are ill and what the nature of their
      disease is. Apart from general preventive health examinations introduced by the
      Federal Joint Committee they are not eligible to diagnostic testing when there
      are no symptoms. Actual suspicion of disease, though, entitles them to diagnostic
      testing services as long as the diagnostic work-up does not show that further
      testing is useless in terms of cure, mitigation or prevention of disease and its
      symptoms. The Social Code Book V (SGB V) does not provide for an independent
      right of information of medical staff, for example, to prevent their acquisition
      of infection. But if the insured claims a medical service associated with a
      specific risk for the medical personnel, e.g. in case of an infectious disease,
      mandatory testing for such a risk can be administered.

PMID- 21958618
TI  - [Does a gain in knowledge with no medical consequences trigger statutory health
      insurance coverage obligation?].
AB  - Patients' self-determination needs to be much more specific and at an earlier
      point in time than is presently the case. We should find ways and methods to
      support this deliberative process. The questions currently explored in studies
      fail to take account of many patients' personal circumstances. It is necessary to
      reflect on the current steps and procedures.

PMID- 21958620
TI  - [Intracerebral aneurysm--treatment options, informed consent, and legal aspects].
AB  - All medical subspecialties and, in particular, high-tech field neurosurgery are
      subject to continuous change in therapeutic concepts due to novel treatment
      options emerging through research and evolution in the field. Hence, the question
      arises if the patient's informed consent needs to be adjusted in the face of
      multiple therapeutic options with different configurations of risk/benefit
      relationships. In this paper we discuss different therapeutic scenarios with
      regard to ruptured intracerebral aneurysms (RIA) and unruptured intracerebral
      aneurysms (UIA), and we advise the medical doctor involved in the process.
      Indeed, experienced neurosurgeons and endovascular interventionalists are very
      familiar with the management of these scenarios; likewise, interns, residents,
      and otherwise affiliated physicians may be faced with these situations. In
      general, asymptomatic and mentally capacitated patients as well as legal
      guardians of minor patients and of mentally incapacitated patients with
      incidental aneurysms and more than one therapeutic option need to be accurately
      informed about the advantages and disadvantages of the treatment options
      available to them. In case of emergency or when treating a mentally disabled
      patient who is incapable of making a sound judgment and has no legal guardian,
      the attending doctor will have to choose the best possible treatment option.

PMID- 21958621
TI  - 'New perspectives on well-known issues': patients' experiences and perceptions of
      safety in Swiss hospitals.
AB  - Patients' reports of safety-related events and perceptions of safety can be a
      valuable source for hospitals. Patients of eight acute care hospitals in
      Switzerland were surveyed for safety-related events and concerns for safety. In
      workshops with hospitals areas for improvement were analyzed and priorities for
      change identified. To evaluate the benefit of the approach, semi-structured
      interviews were conducted with hospital risk managers. 3,983 patients returned
      the survey (55% response rate). 21.4% reported at least one definite safety
      event, and the mean number of 'definite' incidents per patient was 0.31 (95%
      CI=0.29 to 0.34). 3.2% were very concerned and 14.7% were somewhat concerned
      about medical errors and safety. Having experienced a safety-related event,
      younger age, length of stay, poor health and a poor education increased the
      probability of reporting concerns. With some exceptions, results confirmed the
      hospitals' a priori expectations regarding the strengths and weaknesses of their
      institutions. Risk managers emphasized the usability of results for their work
      and the special value of referring to the patient's perspective at their home
      institutions. A considerable fraction of patients subjectively experiences safety
      related events and is concerned about safety. Patient-generated data introduced a
      new quality into the discussion of safety issues within hospitals, and some
      expected that patients' experiences and concerns could affect patient volumes.
      Though the study is limited by the short time horizon and the lack of follow-up,
      the results suggest that the described approach is feasible and can serve as a
      supplemental tool for risk identification and management.

PMID- 21958622
TI  - A comparative analysis of exome capture.
AB  - BACKGROUND: Human exome resequencing using commercial target capture kits has
      been and is being used for sequencing large numbers of individuals to search for
      variants associated with various human diseases. We rigorously evaluated the
      capabilities of two solution exome capture kits. These analyses help clarify the
      strengths and limitations of those data as well as systematically identify
      variables that should be considered in the use of those data. RESULTS: Each exome
      kit performed well at capturing the targets they were designed to capture, which
      mainly corresponds to the consensus coding sequences (CCDS) annotations of the
      human genome. In addition, based on their respective targets, each capture kit
      coupled with high coverage Illumina sequencing produced highly accurate
      nucleotide calls. However, other databases, such as the Reference Sequence
      collection (RefSeq), define the exome more broadly, and so not surprisingly, the
      exome kits did not capture these additional regions. CONCLUSIONS: Commercial
      exome capture kits provide a very efficient way to sequence select areas of the
      genome at very high accuracy. Here we provide the data to help guide critical
      analyses of sequencing data derived from these products.

PMID- 21958623
TI  - How different are the local field potentials and spiking activities? Insights
      from multi-electrodes arrays.
AB  - Simultaneous recording of multiple neurons, or neuron groups, offers new promise
      for investigating fundamental questions about the neural code. We used arrays of
      16 electrodes in the tonotopic, primary, auditory cortex of guinea pigs and we
      extracted LFP- and spike-based spectro-temporal receptive fields (STRFs). We
      confirm here that LFP signals provide broadly tuned activity which lacks
      frequency resolution compared to multiunit signals and, therefore, lead to large
      redundancy in neural responses even between recording sites far apart. Thanks to
      the use of multi-electrode arrays which allows simultaneous recordings, we also
      focused on functional relationships between neuronal discharges (through cross
      correlations) and between LFPs (through coherence). Since the LFP is composed of
      distinct brain rhythms, the LFP results were split into three frequency bands
      from the slowest to the fastest components of LFPs. For driven as well as
      spontaneous activity, we show that components >70 Hz in LFPs are much less
      coherent between recording sites than slower components. In general, coherence
      between LFPs from two recordings sites is positively correlated with the degree
      of frequency overlap between the two corresponding STRFs, similar to cross
      correlation between multiunit activities. However, coherence is only weakly
      correlated with cross-correlation in all frequency ranges. Altogether, these
      results suggest that LFPs reflect global functional connectivity in the
      thalamocortical auditory system whereas spiking activities reflect more
      independent local processing.

PMID- 21958625
TI  - A physics link between venous stenosis and multiple sclerosis.
AB  - This paper hypothesizes that a stenosis or obstruction at a lower extremity of an
      internal jugular vein (IJV) would, in accordance with the physics of fluid
      dynamics, cause a standing pressure wave within the vein. This pressure wave
      would possess regions of large pressure fluctuations and other regions of
      relatively little fluctuation which also have substantially lower peak pressure
      values. If the wavelength of the hypothesized pressure wave is comparable to the
      distance from the obstruction to the venule end of the capillary bed, then a
      region of high pressure fluctuation would exist at the venules. Depending on the
      degree of obstruction, the pressure fluctuations at the venules of the capillary
      bed would be substantially greater than those that would exist in a healthy
      unobstructed vein. This increase in blood pressure fluctuation located at the
      venule end of the capillary bed, which would be equivalent to local hypertension,
      is predicted to reduce the pressure drop across the bed which, in turn, would
      reduce blood flow through the bed in accordance with Darcy's Law. Such a
      reduction in blood flow through the bed would be accompanied by a reduction in
      the transfer of oxygen, glucose and other nutrients into the brain tissue in
      accordance with Fick's Principle. The reduction in oxygen levels in the brain
      tissue (i.e. hypoxia), would, in turn, be associated with increased fatigue and
      decreased mental acuity in the subject patient. Also the deprivation of oxygen in
      the brain tissue may result in the death of oligodendrocyte cells, which, in turn
      would result in the deterioration of the myelin surrounding the brain's neural
      axons. In addition, the paper also predicts that, in cases of extreme
      obstruction, the predicted localized hypertension at the venule end of the
      capillary bed may be sufficiently high to cause a localized disruption in the
      blood-brain barrier. Such a disruption of the blood-brain barrier could then
      allow the migration of leukocytes (auto-immune attack cells), from the blood into
      the brain tissue, enabling them to attack myelin, which has degenerated or
      deteriorated from the reduction in repair function normally provided by
      oligodendrocyte cells. Such leukocyte attack on myelin has long been associated
      with multiple sclerosis.

PMID- 21958624
TI  - Dissecting local circuits in vivo: integrated optogenetic and electrophysiology
      approaches for exploring inhibitory regulation of cortical activity.
AB  - Local cortical circuit activity in vivo comprises a complex and flexible series
      of interactions between excitatory and inhibitory neurons. Our understanding of
      the functional interactions between these different neural populations has been
      limited by the difficulty of identifying and selectively manipulating the diverse
      and sparsely represented inhibitory interneuron classes in the intact brain. The
      integration of recently developed optical tools with traditional
      electrophysiological techniques provides a powerful window into the role of
      inhibition in regulating the activity of excitatory neurons. In particular,
      optogenetic targeting of specific cell classes reveals the distinct impacts of
      local inhibitory populations on other neurons in the surrounding local network.
      In addition to providing the ability to activate or suppress spiking in target
      cells, optogenetic activation identifies extracellularly recorded neurons by
      class, even when naturally occurring spike rates are extremely low. However,
      there are several important limitations on the use of these tools and the
      interpretation of resulting data. The purpose of this article is to outline the
      uses and limitations of optogenetic tools, along with current methods for
      achieving cell type-specific expression, and to highlight the advantages of an
      experimental approach combining optogenetics and electrophysiology to explore the
      role of inhibition in active networks. To illustrate the efficacy of these
      combined approaches, I present data comparing targeted manipulations of cortical
      fast-spiking, parvalbumin-expressing and low threshold-spiking, somatostatin
      expressing interneurons in vivo.

PMID- 21958626
TI  - Ovarian responses and embryo survival in recipient lactating Holstein cows
      treated with equine chorionic gonadotropin.
AB  - The objectives of Experiment 1 were to determine a dose of eCG that would
      increase total luteal volume and plasma progesterone (P4) concentration on
      estrous cycle Day 7 in cows. The objectives of Experiment 2 were to determine the
      effects of treating embryo recipient lactating Holstein cows with eCG on
      pregnancy per embryo transfer (P/ET). In Experiment 1, lactating dairy cows at 63
      +/- 3 d postpartum (DIM) received no treatment (control, n = 10), or 600 (eCG6, n
      = 19), or 800 (eCG8, n = 19) IU of eCG 2 d after the start of the ovulation
      synchronization protocol, Day -8 (Day -10 GnRH, Day -3 PGF(2alpha), Day 0 GnRH).
      Blood was sampled on Days -10, -8, -3, 0, 7, and 14 for P4 concentration. Ovaries
      were examined by ultrasound on Days -10, -3, 0, and 7. In Experiment 2, lactating
      dairy cows were paired according to parity and previous insemination (0 or > 1
      insemination) and assigned to receive 800 IU of eCG (eCG8, n = 152) 2 d after the
      start of the ovulation-synchronization protocol (Day -10 GnRH, Day -3
      PGF(2alpha), Day 0 GnRH) or to receive no treatment (control, n = 162). Blood was
      sampled on Days -10, -3, 0, 7, and 14 for determination of P4 concentration.
      Ovaries were examined by ultrasound on Days -10, -3, and 7, and cows with a CL >
      20 mm in diameter on Day 7 received an embryo. In Experiment 1, P4 concentration
      on Day 7 was higher (P < 0.05) for eCG8 cows (2.3 +/- 0.3 ng/mL) compared with
      control (1.2 +/- 0.3 ng/mL) and eCG6 (1.1 +/- 0.3 ng/mL) cows. In Experiment 2,
      eCG8 primiparous cows had more (P < 0.01) follicles > 10 mm on Day -3 compared
      with control primiparous cows (2.5 +/- 0.9 vs 1.7 +/- 0.5 mm), but multiparous
      control and eCG8 cows did not differ. A larger (P = 0.03) percentage of control
      cows received an embryo (87.5 vs 79.1%) compared with eCG8 cows. Among cows that
      received an embryo, total luteal volume on Day 7 was affected (P = 0.05) by
      treatment (eCG8 = 8.3 +/- 0.4 cm(3), control = 6.2 +/- 0.4 cm(3)), but P4
      concentration on Day 7 did not differ significantly between treatments. The
      percentage of cows pregnant 53 d after ET (overall, 24.2%) was not significantly
      different between control and eCG8 cows. In the current study, no differences in
      P/ET were observed between control and eCG8 cows and treatment with eCG increased
      the percentage of cows with asynchronous estrous cycle.

PMID- 21958627
TI  - Comparison of two commercial extenders for cryopreservation of goat semen without
      sperm washing.
AB  - The objective of this study was to evaluate the effects of two commercially
      available semen extenders on the motility of cryopreserved goat sperm and to
      simplify the cryopreservation protocol. Individual goat ejaculates were split and
      processed in parallel for freezing in either commercially available soy-based
      extender (Bioxcell(r)) or egg yolk-based extender (Irvine TYB). Sperm quality was
      assessed using total and progressive sperm motility, measured by computer
      assisted sperm analysis (CASA). Total motility was higher for samples processed
      in soy-based extender, both at pre-freeze (P = 0.002) and at post-thaw (P <
      0.0001). Progressive motility was higher for semen processed in soy extender at
      post-thaw (P < 0.0001). Approximately 10% of samples processed in egg yolk-based
      extender had a large (> 50%) reduction in total motility prior to freezing.
      However, this type of extreme reduction in pre-freeze motility did not occur in
      semen samples processed in soy extender. In addition, the use of soy-based
      extender eliminated the need for a time-consuming sperm washing protocol. We
      concluded that a commercially available soy-based extender was superior to an egg
      yolk-based extender in preserving motility of cryopreserved goat sperm, using a
      two-step method.

PMID- 21958628
TI  - Non-invasive monitoring of the estrous cycle in captive crab-eating foxes
      (Cerdocyon thous).
AB  - In this study, four crab-eating fox females (Cerdocyon thous) maintained at the
      Federal University of Mato Grosso Zoo, Cuiaba, Brazil, were investigated for 16
      mo, using transabdominal ultrasonography and measurement of estradiol and
      progesterone concentrations in blood plasma and feces. Blood collection and
      ultrasonography were performed once a month, whereas fecal collections were
      performed three times a week. During the experimental period, there was an annual
      estrous cycle in all females, with the reproductive season lasting from winter to
      spring, and three became pregnant. Transabdominal ultrasonography was
      inconclusive for characterization of estrus cycles phase, but was effective for
      early detection of pregnancy, pregnancy monitoring, and for evaluating postpartum
      uterine involution. There were similarities between C. thous female's
      reproductive aspect and bitches, with similar pregnancy data, although uterine
      involution was faster in C. thous. Peak serum concentrations of P4 and E2 were
      (mean +/- SD) 14.58 +/- 5.8 ng/ml and 31.62 +/- 53.54 pg/ml, respectively,
      whereas mean fecal peaks of P4 and E2 were 2.37 +/- 1.42 ng/g and 157.95 +/-
      82.63 pg/g, respectively. All pregnant females had serum and fecal P4
      concentrations reaching maximum values (16.5 +/- 4.0 ng/ml and 2.7 +/- 0.4 ng/g,
      respectively) from 10 to 30 d of gestation; those values subsequently declined,
      reaching baseline at parturition (5.0 +/- 4.0 and 0.7 +/- 0.4 ng/g,
      respectively). Peaks of E2 occurred throughout the year, and were absent only
      during apparent lactational anestrus.

PMID- 21958629
TI  - A review of the risk of contamination of semen and embryos during
      cryopreservation and measures to limit cross-contamination during banking to
      prevent disease transmission in ET practices.
AB  - This review summarizes pertinent data and opinions regarding the potential hazard
      of disease transmission through cryopreserved and banked embryos in liquid
      nitrogen (LN). Special attention is given to the survival of pathogens in LN, new
      vitrification methods, sterility of LN, risks associated with the use of straws
      and cryovials, and LN dewars including dry shippers. It was experimentally
      demonstrated that cross-contamination between LN and embryos may occur, when
      infectious agents are present in LN and embryos are not protected by a sealed
      container. It is important, therefore, to prevent direct contact of embryos with
      LN during cryopreservation and their banking. This includes the usage of
      hermetically sealed, high-quality, shatter-proof freezing containers and/or the
      application of a secondary enclosure such as "double bagging or straw in straw."
      A periodic disinfection of cryo-dewars should be considered as an additional
      precaution to diminish the potential for inadvertent cross-contamination. It
      might be advisable to use separate LN dewars to quarantine embryos derived from
      infected donors of valuable genotype or from unknown health status, extinction
      threatened species. Nevertheless, in summary, it has been concluded that over 25
      yr with no direct evidence of disease transmission by transferred cryopreserved
      human and animal embryos, that the present cryopreservation technology is
      sanitary sound, with the stipulation that biocontainment measures recommended by
      the International Embryo Transfer Society (IETS) and the World Organization for
      Animal Health - Office International des Epizooties (OIE), are strictly followed.

PMID- 21958630
TI  - Effects of sex control and twinning on economic optimization of culling cows in
      Japanese Black cow-calf production systems.
AB  - The effects of sex control and twinning techniques on determination of optimal
      culling parity of cows in beef cow-calf production systems were deterministically
      analyzed using a herd model simulation. The model simulated the annualized net
      revenue as an economic indicator during the whole life cycle of a cow. Biological
      factors (survivability, growth, reproduction, and feed requirements) and economic
      factors (returns from sales of live calves and cows' carcasses and production
      costs) were included in the model. Some biological and economic parameters
      relating to these factors were altered from a base condition in order to adapt
      the production systems with sex control and twinning techniques. Based on the
      model, early culling was optimal for all production systems when biological
      efficiency was used as an indicator of production; however, later culling was
      optimal for single production, but slightly earlier culling was optimal for twin
      production, when annualized net revenue was evaluated. The introduction of sex
      control did not greatly affect the determination of the optimal culling parity of
      cows. When production included the sex control, female sexing increased
      biological efficiency, whereas male sexing increased annualized net revenue. In
      the present beef cow-calf production circumstances in Japan, introduction of sex
      control did not have economically appreciable effects, but twinning was
      economically beneficial. For production involving sex control, improvement in the
      conception rate per mating and/or reduction of technical cost were required for
      this technology to be profitable.

PMID- 21958631
TI  - The risk of introduction of equine infectious anemia virus into USA via cloned
      horse embryos imported from Canada.
AB  - Deriving horse oocytes in the USA is hampered by the lack of abattoirs processing
      horse carcasses which could provide abundant quantities of ovaries from
      slaughtered mares. Therefore, several cloning industries in the USA are
      attempting to import cloned horse embryos from Canada. Like any agricultural
      commodity, cloned embryos pose a risk of introduction of exotic animal diseases
      into the importing country. Under such circumstances, risk assessment could
      provide an objective, transparent, and internationally accepted means for
      evaluating the risk. This quantitative risk assessment (QRA) was initiated to
      determine the risk of introduction of Equine infectious anemia virus (EIAV) into
      the USA via cloned horse embryos imported from Canada. In assessing the risk, a
      structured knowledge base regarding cloning in relation to Equine infectious
      anemia (EIA) was first developed. Based on the knowledge base, a scenario tree
      was developed to determine conditions (with mathematical probabilities) that
      could lead to the introduction and maintenance of EIAV along the cloning pathway.
      Parameters for the occurrence of the event at each node were estimated using
      published literature. Using @Risk software and setting Monte Carlo simulation at
      50,000 iterations, the probability of importing an EIAV-infected cloned horse
      embryo was 1.8 * 10(-9) (R = 1.5 * 10(-12) to 2.9 * 10(-8)). Taking into account
      the current protocol for equine cloning and assuming the yield of 5 to 30 clones
      per year, the possible number of EIAV-infected cloned horse embryos ranged from
      2.0 * 10(-10) to 9.1 * 10(-5) (Mean = 1.4*10(-6)) per year. Consequently, it
      would take up to 1.5 * 10(7) (R = 1.6 * 10(4) to 5.1 * 10(10)) years for EIAV to
      be introduced into the USA. Based on the knowledge base and our critical pathway
      analysis, the biological plausibility of introducing EIAV into USA via cloned
      horse embryos imported from Canada is extremely low.

PMID- 21958632
TI  - Prostaglandin F2alpha and control of reproduction in female swine: a review.
AB  - In female swine, PGF2alpha is an important regulator of corpora luteal (CL)
      function, uterine contractility, ovulation, and embryo attachment. High affinity
      PGF2alpha receptors are present in the CL at all stages of the estrous cycle and
      they are functional. Therefore, a lack of luteolytic capacity of PGF2alpha is
      related to other factors that have not been well identified. In female pigs, a
      single exogenous PGF2alpha injection produces a short lasting decrease in plasma
      progesterone levels but does not induce luteolysis before day 12 of the estrous
      cycle. However, multiple injections of PGF2alpha can induce luteolysis before day
      12 of the estrous cycle and may be utilized in the development of protocols for
      ovulation synchronization and timed AI. Most commonly, PGF2alpha is used for the
      induction of farrowing and so facilitation of cross fostering. Further, since
      PGF2alpha is a smooth muscle stimulant, treatment to stimulate myometrial
      contractions and uterine evacuation of residual products from parturition or
      infectious debris, may have beneficial effects on post-weaning fertility.
      Administration of PGF2alpha at the moment of insemination has been shown to
      improve reproductive performances when fertility is otherwise low, such as in sow
      under summer heat stress.

PMID- 21958634
TI  - Ram seminal plasma improves pregnancy rates in ewes cervically inseminated with
      ram semen stored at 5  degrees C for 24 hours.
AB  - In this study, we compared pregnancy rates obtained using ram semen stored at 5 
      degrees C for 24 h, with ram or bull seminal plasma (SP) added to TRIS-egg yolk
      extender. During the breeding period, 670 adult Corriedale ewes were cervically
      inseminated with semen (2 * 10(8) sperm in a volume of 0.2 mL) from eight adult
      Corriedale rams. Ejaculates, obtained using an artificial vagina, were split into
      three aliquots and diluted with the following: TRIS-egg yolk based extender (T),
      T + 30% ram SP (R), or T + 30% bull SP (B). Samples were refrigerated and stored
      at 5  degrees C for 24 h until used for AI. Pregnancy was assessed by
      ultrasonography 35 to 40 d after AI. Pregnancy rate was not affected by ram (P =
      0.77) or breeding period (P = 0.43), and there were no interactions between
      extender and ram (P = 0.94), or extender and breeding period (P = 0.24). However,
      there was an effect of extender (P = 0.0009) on pregnancy rates; ram SP, but not
      bull SP, increased pregnancy rates compared with extender without SP (49.7, 38.1,
      and 31.1%, for R, B, and T respectively). In conclusion, ram SP added to TRIS-egg
      yolk extender had a beneficial effect on the pregnancy rate of ram sperm stored
      at 5  degrees C for 24 h and used for cervical insemination of ewes.

PMID- 21958633
TI  - Fertility-associated antigen on Nelore bull sperm and reproductive outcomes
      following first-service fixed-time AI of Nelore cows and heifers.
AB  - The objective was to determine whether the presence of fertility-associated
      antigen (FAA) on sperm collected from Nelore (Bos indicus) bulls can be used to
      assess potential fertility of sperm for use at first-service fixed-time AI (TAI).
      Six Nelore bulls were selected based on FAA status (FAA-negative: N = 3; FAA
      positive: N = 3) and the ability to produce neat semen with >= 70%
      morphologically normal sperm and 60% estimated progressive motility before
      cryopreservation. In Experiment 1, suckled multiparous Nelore cows (N = 835) were
      evaluated for body condition score (BCS) and received an intravaginal
      progesterone device (CIDR) and 2.0 mg of estradiol benzoate (Day 0). On Day 9 the
      CIDR was removed, 12.5 mg of PGF(2alpha) and 0.5 mg of estradiol cypionate were
      administered, and calves were removed for 48 h. All cows received TAI on Day 11
      (48 h after CIDR removal). Pregnancy per TAI (P/TAI) was not different between
      FAA-positive and FAA-negative bulls (41.5% vs. 39.3%, respectively). There was an
      effect of AI technician on P/TAI (36.0% vs. 43.9%; P < 0.05) and BCS tended to
      affect P/TAI (P = 0.09), as cows with BCS >= 2.75 were 1.4 times more likely to
      become pregnant compared with cows with BCS < 2.75. In Experiment 2, nulliparous
      Nelore heifers (N = 617) were evaluated for BCS and received a CIDR and estradiol
      benzoate (2.0 mg) on Day 0. On Day 7, all heifers received PGF(2alpha) (12.5 mg).
      On Day 9, CIDR inserts were removed and all heifers received estradiol cypionate
      (0.6 mg) and 200 IU eCG. All heifers received TAI on Day 11 (48 h after CIDR
      removal). Pregnancy/TAI was different (P = 0.04) between FAA-positive and FAA
      negative bulls (33.7% vs. 40.7%, respectively). Presence of FAA on sperm was
      unsuccessful in assessing the potential fertility of sperm for use in TAI.

PMID- 21958635
TI  - Uterine artery blood flow remains unchanged in pregnant mares in response to
      short-term administration of pentoxifylline.
AB  - The objective of this study was to use Doppler ultrasound technology to determine
      whether pentoxifylline administration increased uterine blood flow in normal
      pregnant pony mares. Thirteen pregnant pony mares between 18 and 190 d of
      gestation (mean +/- SEM, 101 +/- 55) were utilized for the study during two trial
      periods. In each trial, pentoxifylline (17 mg/kg by mouth every 12h, diluted in
      syrup) was administered to half of the mares for 3 d, while the other mares were
      treated with syrup only. Doppler measurements were obtained from the right and
      left uterine arteries from each mare for 2 d prior to treatment and throughout
      the treatment period. The mean Resistivity Index (RI), Pulsatility Index (PI),
      Uterine Artery Diameter (D), and Total Arterial Blood Flow (TABF) from each day
      were compared over time and between groups. Administration of pentoxifylline did
      not alter uterine blood flow parameters compared with controls (values for all
      treatment days combined were RI: 0.517 +/- 0.014 vs 0.543 +/- 0.016; PI: 0.876 +/
      0.048 vs 0.927 +/- 0.057; D: 0.388 +/- 0.018 vs 0.379 +/- 0.023 cm; and TABF:
      35.26 +/- 7.38 vs 30.73 +/- 5.29 mL/min). Uterine blood flow increased over the
      course of the 5 d study, irrespective of treatment, and was higher in mares of
      greater gestational age than in early gestational mares (RI: r(2) = 0.35; PI:
      r(2) = 0.37; D: r(2) = 0.66; and TABF: r(2) = 0.67 - P < 0.00001). We concluded
      that any immediate benefits of pentoxifylline administration in the pregnant mare
      were not mediated through enhanced uterine artery blood flow.

PMID- 21958636
TI  - Effects of copper sulphate concentrations during in vitro maturation of bovine
      oocytes.
AB  - THE OBJECTIVES WERE TO EVALUATE: 1) copper (Cu) concentrations in plasma and
      follicular fluid (FF) from cattle ovaries; 2) the effects of supplemental Cu
      during in vitro maturation (IVM) on DNA damage of cumulus cells and glutathione
      (GSH) content in oocytes and cumulus cells; and 3) supplementary Cu during IVM on
      subsequent embryo development. Copper concentrations in heifer plasma (116 +/-
      27.1 MUg/dL Cu) were similar (P > 0.05) to concentrations in FF from large (90 +/
      20.4 MUg/dL Cu) and small (82 +/- 22.1 MUg/dL Cu) ovarian follicles in these
      heifers. The DNA damage in cumulus cells decreased with supplemental Cu
      concentrations of 4 and 6 MUg/mL (P < 0.01) in the IVM medium (mean +/- SEM index
      of DNA damage was: 200.0 +/- 27.6, 127.6 +/- 6.0, 46.4 +/- 4.8, and 51.1 +/- 6.0
      for supplementation with 0, 2, 4, and 6 MUg/mL Cu respectively). Total GSH
      concentrations increased following supplementation with 4 MUg/mL Cu (4.7 +/- 0.4
      pmol in oocytes and 0.4 +/- 0.04 nmol/10(6) cumulus cells) and 6 MUg/mL Cu (5.0
      +/- 0.5 pmol in oocytes and 0.5 +/- 0.05 nmol/10(6) cumulus cells, P < 0.01)
      compared with the other classes. Cleavage rates were similar (P >= 0.05) when Cu
      was added to the IVM medium at any concentration (65.1 +/- 2.0, 66.6 +/- 1.6,
      72.0 +/- 2.1, and 70.7 +/- 2.1 for Cu concentrations of 0, 2, 4, and 6 MUg/mL).
      Percentages of matured oocytes that developed to the blastocyst stage were 18.7
      +/- 0.6, 26.4 +/- 0.03, and 29.0 +/- 1.7% for 0, 2, and 4 MUg/mL Cu, and was
      highest (33.2 +/- 1.6 %) in oocytes matured with 6 MUg/mL Cu (P > 0.01). There
      was an increase (P > 0.05) in mean cell number per blastocyst obtained from
      oocytes matured with 4 and 6 MUg/mL Cu relative to 0 Cu (IVM alone) and 2 MUg/mL
      Cu. In conclusion, Cu concentrations in the FF and plasma of heifers were
      similar. Adding copper during oocyte maturation significantly increased both
      intracellular GSH content and DNA integrity of cumulus cells. Since embryo
      development was responsive to copper supplementation, we inferred that optimal
      embryo development to the blastocyst stage was partially dependent on the
      presence of adequate Cu concentrations during IVM.

PMID- 21958637
TI  - Generation and characterization of reprogrammed sheep induced pluripotent stem
      cells.
AB  - Embryonic stem cells (ESCs) from domestic species have numerous potential
      applications in agricultural and biomedical sciences; however, despite intensive
      efforts, derivation of ESCs from sheep remains elusive. The objective was to
      derive sheep induced pluripotent stem cells (iPSCs), as an alternative
      pluripotent cell type to ESCs, from sheep fibroblasts by ectopic expression of
      heterologous transcription factors OCT4, SOX2, KLF4, and cMYC. Sheep fibroblasts
      were infected with pantropic retroviruses coding the four transcription factors
      and reprogrammed to pluripotency at a rate of 0.002%. The sheep iPSCs (siPSCs)
      reactivated endogenous OCT4 and SOX2 genes assessed by qRT-PCR and immuno
      cytochemistry, retained normal karyotyping, and more importantly, concurrently
      silenced all exogenous transgenes. The siPSCs were enzymatically dissociated to
      single cells, making them amenable to efficient transfection and fluorescent
      activated cell sorting techniques. Further, the siPSCs differentiated in vitro to
      form embryoid bodies, and in vivo to form robust teratomas, containing cells
      representative of the three germ layers. Moreover, when injected into diploid or
      tetraploid sheep embryos, siPSCs contributed to the inner cell mass of resulting
      blastocysts, suggesting true pluripotential. These reprogrammed siPSCs may
      constitute a robust pluripotent alternative to elusive sheep ESCs, with great
      potential for use in agriculture and pharmaceutical biotechnology.

PMID- 21958638
TI  - Slow-controlled freezing versus speed-cooling for cryopreservation of whole
      guinea pig ovaries.
AB  - The objective of this study was to evaluate the feasibility of whole-ovary
      perfusion, and to compare the effects of speed-cooling and slow-controlled
      freezing of whole guinea pig ovaries. Slow-freezing and speed-cooling procedures
      were performed after perfusion of guinea pig ovaries with cryoprotectants. Ink
      perfused via the vascular pedicles was present in the microvessels around various
      follicles at various stages of development in the cortical and medullar regions,
      thereby confirming that perfusion was effective. Vascular damage was essentially
      confined to the cannulated artery. Based on histological examination, there were
      (mean +/- SEM) 93.1 +/- 4.2, 79.0 +/- 2.0, and 54.7 +/- 8.5% healthy follicles in
      the fresh, slow-freezing and speed-cooling groups, respectively (each group
      differed from the other two, P < 0.05). Trypan blue staining of isolated
      follicles confirmed that cellular damage was greater following speed-cooling than
      slow-freezing (58.6 vs 29.2%, P < 0.05). Based on a TUNEL assay, speed-cooling
      caused more apoptotic granulosa and theca cells in antral follicles than slow
      freezing. In conclusion, the present study provided evidence that guinea pig
      whole ovaries could be perfused with cryoprotectant and cryopreserved in vitro.
      Furthermore, the slow-freezing protocol resulted in less cellular damage in
      thawed tissues than speed-cooling.

PMID- 21958639
TI  - Ultrasonographic features of the mule embryo, fetus and fetal-placental unit.
AB  - The aim of this study was to establish baseline ultrasound data concerning the
      mule conceptus during gestation. Ten multiparous Trotter mares were artificially
      inseminated with chilled semen from an Amiatino jack donkey. Daily transrectal
      ultrasonography was carried out from the day of ovulation until Day 50 of
      gestation to determine the following: first detection of the embryonic vesicle
      (EV), mobility phase, EV diameter, day of EV fixation, changes in EV shape, date
      of yolk sac regression and embryo crown-rump length. Monthly ultrasonic
      assessments from Day 50 of gestation to term were carried out. These assessments
      included an evaluation of fetal well-being and the growth of the mule conceptus,
      which were monitored using the following variables: cardiac activity, fetal
      activity and presentation, fetal fluid echogenicity, combined thickness of the
      utero-placenta unit and fetal orbital and aortic diameter. Mule EV first
      detection was observed earlier (37% at Day 8) than that observed in the equine
      pregnancy. EV diameter at first detection was 4.6 +/- 1.1 mm. At Day 10, 75% of
      EVs were detected. EV fixation occurred on Day 17.1 +/- 1.1, with a mean EV
      diameter of 2.5 +/- 0.2 cm. EV growth rate was 4.04 mm/day from Days 11 to 16,
      0.4 mm/day from Days 16 to 28 and 1.78 mm/day from Days 28 to 45 of pregnancy.
      The embryo proper was first detected on Day 19.9 +/- 1.9 (average length 2.4 +/-
      1.4 mm), and the embryonic heartbeat was first detected on Day 24 +/- 2.4. The
      fetal carotid pulse was observed at six months of gestation and provided a good
      means by which to estimate fetal cardiac activity in advanced gestation. The
      fetal heart rate was recorded from Month 2 of gestation to term. The mean +/- SD
      of the combined uteroplacental thickness was assessed at the cervical-placental
      junction and at the ventral abdomen in mares between Months 2 and 5 until term,
      respectively. An abnormal fetal-placental unit and fetal inactivity was observed
      in association with abortion. Mule-conceptus biometric measurements correlated
      significantly with the gestational age, and these data were used to predict an
      unusually large mule fetus, which might result in dystocia. In conclusion, we can
      assume that early diagnosis of pregnancy failure and assessment of fetal
      biophysical profile and growth charts could improve the chances of gestation
      completion in mule-pregnant mares. The early detection of mares at risk for an
      abnormal pregnancy or delivery may increase the success of prompt treatments,
      therefore preventing costly emergency procedures and allowing proper obstetrical
      and neonatal assistance.

PMID- 21958640
TI  - Effects of different storage protocols on cat testis tissue potential for
      xenografting and recovery of spermatogenesis.
AB  - The loss of genetic diversity due to premature death of valuable individuals is a
      significant problem in animal conservation programs, including endangered felids.
      Testis tissue xenografting has emerged as a system to obtain spermatozoa from
      dead immature animals, however protocols to store this tissue before xenografting
      are still lacking. This study focused on testis tissue cryopreservation and
      storage from the domestic cat (Felis catus) classified as "pre-pubertal" and
      "pubertal" according to spermatogenesis development. Grafts from testis tissue
      cryopreserved with DMSO 1.4M, recovered after 10 weeks xenografting, presented
      seminiferous tubules with no germ cells. On the contrary, testis tissue from pre
      pubertal animals preserved in ice-cold medium for 2 to 5 days presented no loss
      of viability or spermatogenic potential, while the number of grafts of pubertal
      cat testis tissue with germ cells after 10 weeks of xenografting decreased with
      increasing storage time. Nevertheless, even grafts from pre-pubertal cat testis
      tissue presented lower anti-DDX4 and anti-BOULE staining (proteins necessary for
      the meiosis completion), when compared with adult cat testis. Finally, a strong
      correlation found between testis weight and xenograft outcome may help choose
      good candidates for xenografting.

PMID- 21958641
TI  - Ovulating induction methods in rabbit does: the pituitary and ovarian responses.
AB  - The aim of this study was to compare the pituitary and ovarian responses in
      rabbit does subjected to different methods of ovulation induction. Forty-eight
      receptive females were randomly distributed into six groups (N = 8) and were
      inseminated with standard glass catheters. Buserelin intramuscular (BM) does were
      inseminated using a pool of fresh heterospermic semen and an intramuscular
      injection of 1 MUg of buserelin acetate to induce ovulation. Buserelin
      intravaginal (BV) does were inseminated in a similar way, but ovulation was
      induced with the GnRH analogue (10 MUg of buserelin acetate) combined with 0.5 mL
      of semen extender. The raw semen (R) and saline groups (S) were inseminated with
      undiluted semen or saline, respectively, without any inducer of ovulation.
      Another group (A) received lumbar anaesthesia (1.5 mL of 2% lidocaine), and only
      the empty catheter was introduced into the vagina. The AR does were treated the
      same way as group A but were inseminated with raw semen instead of an empty
      catheter. Blood samples were collected to determine the LH concentrations before
      and after AI (30, 60, 90, and 120 minutes). Ovulation, pregnancy, and conception
      rates were determined after euthanasia on day 14 post AI. Ovulating does had
      higher mean LH concentrations than nonovulating does (197.9 vs. 45.9 ng/mL; P <
      0.05). The ovulation rates of buserelin intramuscular and intravaginal does were
      100%, and the pregnancy rates were 87.5% and 100%, respectively. Rabbit does in
      groups A and AR did not ovulate and had similar mean plasma LH concentrations
      after 60 minutes compared with the S group (49.4 and 49.2 ng/mL vs. 41.6 ng/mL,
      respectively), which reached ovulation and pregnancy rates of 37.5%. Does
      inseminated only with raw semen had an ovulation rate of 75% and a pregnancy rate
      of 62.5%; they also demonstrated higher plasma LH concentrations than does of the
      S, A, and AR groups. In conclusion, ovulation in rabbit does can be induced by
      exogenous GnRH administration (im and intravaginal). The high plasma LH
      concentration and ovulation rate in the R group with respect to the S and A
      groups could weakly indicate the presence of some molecules in the seminal plasma
      that could act on or be absorbed by vaginal mucosa. Sensory stimulation and
      "seminal factors" probably exert a synergy on the ovulation response as
      demonstrated by the comparison of LH release and the ovulation response in the R,
      S, RA, and A groups.

PMID- 21958642
TI  - Factors affecting the occurrence of postpartum prolonged luteal activity in
      clinically healthy high-producing dairy cows.
AB  - The objective was to characterize risk factors affecting the occurrence of
      prolonged luteal phase (PLP) in postpartum, clinically healthy, high-producing
      dairy cows. Transrectal ultrasound examinations of the reproductive tract were
      performed twice weekly, from the 1st to 8th wk after calving in 151 multiparous
      clinically healthy lactating Holstein cows (mean +/- SD of peak milk yield = 56.7
      +/- 7.4 kg). Serum samples were collected twice weekly to measure progesterone
      and every 2 wk to detect beta-hydroxybutyrate (betaHB), and alpha1-acid
      glycoprotein (AGP). Body condition score (BCS) was recorded weekly after calving.
      Based on the serum progesterone profile, 52 (34.4%) cows had normal ovarian
      activity (NLA), whereas 36 (23.8%) cows had a prolonged luteal phase (PLP), the
      most prevalent type of abnormal pattern of luteal activity. Furthermore, 63 cows
      with short luteal activity, delayed first ovulation, or cystic ovaries were
      excluded from this study. Serum AGP concentrations, as an indication of
      postpartum chronic endometritis, were not different (P > 0.05) between cows with
      NLA and PLP. Categories of peak milk yields (kg) were positively correlated with
      the incidence (%) of cows with PLP (r = 0.87, P = 0.02). Furthermore, milk yield
      peak, day of milk yield peak, mean milk yield (8 wk in milk), and milk yield on
      the expected day of luteolysis were higher (P < 0.05) in cows with PLP than NLA,
      and cows with PLP had greater loss of BCS (P = 0.007) than those with NLA. The
      likelihood of cows with PLP decreased by 0.9-fold for every 1 d delay of
      commencement of luteal activity (C-LA). Moreover, the likelihood of cows with PLP
      increased by 1.8-fold for each 1 mmol/L increase in the 1st wk serum betaHB
      concentrations. In conclusion, higher mean of milk yield, greater BCS loss,
      earlier C-LA, and later peak milk yield were the major risk factors affecting the
      occurrence of postpartum PLP in clinically healthy, high-producing dairy cows.

PMID- 21958643
TI  - The novel use of modified pig zygotic medium for the efficient culture of the
      preimplantation mouse embryos.
AB  - A high potassium concentration in culture media is considered detrimental to in
      vitro culture of mouse embryos. Here we show that pig zygotic medium (PZM)
      containing a higher concentration of potassium, and modified to contain 0.2 mM
      glucose and 0.01 mM EDTA, supported efficient pre- and post-implantation
      development of mouse zygotes to blastocysts and live pups, respectively. At
      first, modified PZM (mPZM) was compared with other culture media such as M16, CZB
      and KSOM-AA for its ability to support development of in vivo mouse zygotes to
      the blastocyst stage. The proportions of zygotes reaching 2-cell (94-99%) and
      blastocyst (90-96%) stages in mPZM and other media were not different. However,
      hatching rates of blastocysts were different (P < 0.05); whereas more than 90% of
      the blastocysts were hatching in mPZM or KSOM-AA, only 60% of the blastocysts did
      in M16 or CZB media (P < 0.05). Next we compared post-implantation development of
      in vitro fertilized zygotes developed to blastocysts in mPZM and KSOM-AA. The
      proportion of blastocysts developing into live pups was not different between
      mPZM (49%) and KSOM-AA (44%). Finally, we evaluated whether mPZM could be also
      used as a fertilization medium. Modified PZM containing 5.56 mM of glucose and
      0.4% BSA efficiently supported IVF of mouse gametes. The percent of zygotes
      cleaving to 2-cell (94-98%) and blastocysts (91-93%) stage was not different from
      zygotes fertilized in human tubal fluid medium. We concluded that modified pig
      zygotic medium containing a higher potassium concentration than any other
      commonly used mouse media supported not only culture of mouse embryos, but also
      efficient IVF of mouse gametes.

PMID- 21958644
TI  - Managing the dominant follicle in lactating dairy cows.
AB  - Reproductive efficiency is not optimal in high-producing dairy cows. Although
      many aspects of ovarian follicular growth in cows are similar to those observed
      in heifers, there are numerous specific differences in follicular development
      that may be linked with changes in reproductive physiology in high-producing
      lactating dairy cows. These include: 1) reduced circulating estradiol (E2)
      concentrations near estrus, 2) ovulation of follicles that are larger than the
      optimal size, 3) increased double ovulation and twinning, and 4) increased
      incidence of anovulation with a distinctive pattern of follicle growth in
      anovular dairy cows. The first three changes become more dramatic as milk
      production increases, although anovulation has not generally been associated with
      level of milk production. To overcome reproductive inefficiencies in dairy cows,
      reproductive management programs have been developed to synchronize ovulation and
      enable the use of timed AI in lactating dairy cows. Effective regulation of the
      CL, follicles, and hormonal environment during each part of the protocol is
      critical for optimizing these programs. This review discusses the distinct
      aspects of follicular development in lactating dairy cows and the methodologies
      that have been utilized in the past two decades in order to manage the dominant
      follicle during synchronization of ovulation and timed AI programs.

PMID- 21958645
TI  - Ultrasound characteristics of experimentally induced luteinized unruptured
      follicles (LUF) and naturally occurring hemorrhagic anovulatory follicles (HAF)
      in the mare.
AB  - The development of hemorrhagic anovulatory follicles (HAF) involves luteinization
      and hemorrhage of the follicle. This is observed on ultrasound as an increase in
      the echogenicity of the granulosa layer and formation of echoic particles in the
      antrum. The inhibition of prostaglandin synthesis with flunixin meglumine (FM)
      during the periovulatory period induces ovulatory failure with development of
      luteinized unruptured follicles (LUF). These two types of anovulatory follicles
      appear to share similar ultrasound features but they have not been compared
      critically. The following endpoints: follicle diameter, follicular contents
      score, interval from hCG administration to beginning of follicular hemorrhage,
      interval from hemorrhage to organization of follicular contents, and cycle length
      were studied and compared in mares with HAF (n = 11) and LUF (n = 13). The
      objective of this study was to elucidate whether these two unruptured follicles
      have a consistent clinical pattern of development and therefore can be considered
      as part of the same anovulatory syndrome. None of the endpoints analyzed differed
      significantly between HAF and LUF. However, there was a greater individual
      variation in HAF as compared with LUF in regards to interval from hCG to
      hemorrhage, follicular diameter at the administration of hCG, and beginning of
      hemorrhage. In conclusion, HAF share a similar cascade of ultrasound
      characteristics with the experimentally induced LUF. This finding may provide new
      insights in elucidating the pathogenesis of HAF.

PMID- 21958646
TI  - Tongue corticospinal modulation during attended verbal stimuli: priming and
      coarticulation effects.
AB  - Humans perceive continuous speech through interruptions or brief noise bursts
      cancelling entire phonemes. This robust phenomenon has been classically
      associated with mechanisms of perceptual restoration. In parallel, recent
      experimental evidence suggests that the motor system may actively participate in
      speech perception, even contributing to phoneme discrimination. In the present
      study we intended to verify if the motor system has a specific role in speech
      perceptual restoration as well. To this aim we recorded tongue corticospinal
      excitability during phoneme expectation induced by contextual information.
      Results showed that phoneme expectation determines an involvement of the
      individual's motor system specifically implicated in the production of the
      attended phoneme, exactly as it happens during actual listening of that phoneme,
      suggesting the presence of a speech imagery-like process. Very interestingly,
      this motoric phoneme expectation is also modulated by subtle coarticulation cues
      of which the listener is not consciously aware. Present data indicate that the
      rehearsal of a specific phoneme requires the contribution of the motor system
      exactly as it happens during the rehearsal of actions executed by the limbs, and
      that this process is abolished when an incongruent phonemic cue is presented, as
      similarly occurs during observation of anomalous hand actions. We propose that
      altogether these effects indicate that during speech listening an attentional
      like mechanism driven by the motor system, based on a feed-forward anticipatory
      mechanism constantly verifying incoming information, is working allowing
      perceptual restoration.

PMID- 21958647
TI  - Longitudinal trajectories of gestural and linguistic abilities in very preterm
      infants in the second year of life.
AB  - The present study involved a systematic longitudinal analysis, with three points
      of assessment in the second year of life, of gestures/actions, word
      comprehension, and word production in a sample of very preterm infants compared
      to a sample of full-term infants. The relationships among these competencies as
      well as their predictive value on language development at 24 months and the
      contribution of biological, medical and social risk factors on language delay at
      24 months were also analysed. One hundred and four monolingual Italian very
      preterms (mean gestational age 29.5 weeks) without major cerebral damages, and a
      comparison group of 20 monolingual healthy Italian full-terms were followed at
      12, 18 and 24 months by administering to their parents the Italian short forms of
      the MacArthur-Bates CDI. Preterms showed a slower acquisition in gesture/action
      production, word comprehension, and word production with an increasing divergence
      with respect to full-terms from 12 to 24 months, when 20% of preterms were
      delayed in word production (<10th percentile) and 14% did not combine words yet.
      Lexical competencies at 12 months and together with gestures/actions at 18 months
      were predictive of word production at 24 months, with a stronger contribution of
      word comprehension at 12 months and of word production at 18 months. Male gender,
      bronchopulmonary dysplasia, and low maternal educational level increased the risk
      of language delay at 24 months. Our findings suggest there to be a slower rate of
      communicative-linguistic development in very preterms with an increasing
      difference in their gestural and lexical competencies in the second year of life
      with respect to full-terms. The interplay of the above competencies and
      biological, medical and social risk factors increase the risk of language delay
      at 24 months in very preterm infants.

PMID- 21958648
TI  - Relationship between occupation attributes and brain metabolism in frontotemporal
      dementia.
AB  - Occupation has been associated with cognitive reserve in healthy aging and
      Alzheimer's disease. Here we assess the relationship between cerebral metabolic
      deficits in behavioral variant frontotemporal dementia (bvFTD) and occupation
      characteristics. Using factor analysis, we derived verbal, physical and
      visuospatial occupation scores from the US Department of Labor, Occupational
      Information Network and related these scores to regional cerebral metabolic rate
      of glucose utilization in 31 patients diagnosed with behavioral variant bvFTD,
      controlling for cognitive status (CERAD neuropsychological assessment battery),
      gender and education. Regression analyses showed a marked inverse association
      between glucose metabolism and (a) verbal occupation scores in left prefrontal
      cortex and, (b) physical occupation characteristics in right supplementary motor
      area. We concluded that, consistent with the cognitive reserve hypothesis,
      lifelong occupation characteristics are related to focal cerebral metabolic
      deficits in bvFTD. Specific occupation demands spanning decades may strengthen
      cognitive resistance to pathology.

PMID- 21958649
TI  - Neuroimaging reveals enhanced activation in a reach-selective brain area for
      objects located within participants' typical hand workspaces.
AB  - In recent years, there has been growing excitement within cognitive neuroscience
      about the concept of embodiment: How do the capabilities and limitations of our
      physical bodies affect neural representations in the brain? Neuropsychological
      and neurophysiological studies show clear evidence that short-term visuomotor
      experience can influence the encoding of the space around the body in parietal
      cortex. For example, tool-use may expand the neural representation of
      peripersonal space. But how is this initial spatial representation influenced by
      a lifetime of object-related interactions? To examine this question we used
      functional magnetic resonance imaging (fMRI) to investigate the neural effects of
      an individual's hand preferences for acting within peripersonal space. Left- and
      right-handed participants viewed real-world objects at different locations
      accessible by either the left hand, right hand, or neither hand. The superior
      parieto-occipital cortex (SPOC), an area most often implicated in reaching
      actions, showed enhanced visual responses for objects located within the range of
      space in which each group typically acts. Specifically, in right-handers, who
      strongly prefer grasping with the right hand, SPOC showed strongest activation
      for objects located within the range of space for the right hand only. In
      contrast, in left-handers, who use their two hands comparably often in visuomotor
      tasks, SPOC showed strongest activation for objects located within the range of
      space of either hand. These findings show that, even in the absence of overt
      responses, real 3D objects located in the individual's typical workspace for hand
      actions automatically invoke enhanced responses in associated visuomotor areas of
      the brain.

PMID- 21958650
TI  - Encoding: the keystone to efficient functioning of verbal short-term memory.
AB  - Verbal short-term memory (VSTM) is thought to play a critical role in language
      learning. It is indexed by the nonword repetition task where listeners are asked
      to repeat meaningless words like 'blonterstaping'. The present study investigated
      the effect on nonword repetition performance of differences in efficiency of
      functioning of some part of the neural architecture mediating VSTM. Hypotheses
      were stated within Baddeley and Hitch's (1974) multicomponent model of VSTM, with
      respect to regions of the brain known to be active during tasks tapping into
      VSTM. We were specifically interested in activations associated with the
      posterior planum temporale (Spt) which emerge during rehearsal since this region
      is hypothesized to be central to VTSM (Buchsbaum, Olsen, Koch, & Berman, 2005a).
      Participants performed a delayed reaction time task in the scanner which
      explicitly mimicked the three main stages of information-processing involved in
      VSTM (encoding, rehearsal, recall (here recognition)). The data for each stage
      were then convolved with scores from a separately measured nonword repetition
      task. Rather than observing a pattern of individual differences located to
      specific regions specialized for supporting VSTM, a dissociation in direction of
      correlation in overlapping regions of the brain was observed during encoding and
      recognition. Larger hemodynamic responses during encoding were associated with
      better nonword repetition, and vice versa during recognition. There was little
      evidence for a network of activations specialized for VSTM. Instead, the main
      correlations were observed in regions also known to be involved in long-term
      memory. It seems that individuals who are better at nonword repetition and hence
      at language learning, activate these regions more efficiently than poorer nonword
      repeaters early after stimulus input. These observations are discussed with
      respect to various models proposed for explaining the phenomenon of VSTM.

PMID- 21958651
TI  - Subcortical contributions to effective connectivity in brain networks supporting
      imitation.
AB  - Using functional magnetic resonance imaging (fMRI), we investigated effective
      connectivity in brain networks supporting imitation. Despite extensive reports of
      regional functional specialization underlying action perception, action execution
      and imitation, our understanding of the potential contribution of subcortical
      sites is limited, as is our knowledge of how regions displaying functional
      specialization interact with each other on a system level. While in the scanner,
      participants performed a simple imitation paradigm with three conditions: Observe
      trials, in which participants passively viewed a human actor executing a sequence
      of four finger presses on a keypad; Imitate trials, in which participants
      imitated the actor's finger presses on a keyboard; and Execute trials, in which
      participants also executed finger presses but did so based on visuospatial cues
      in the absence of the actor's hand. Relative to the Execute condition, Imitate
      trials evoked significantly more activity in superior and inferior parietal
      lobules (SPL, IPL), posterior superior temporal sulcus (pSTS), and in a ventral
      aspect of dorsal premotor cortex (PMd). Psychophysiological interaction (PPI)
      analysis, a means of assessing effective connectivity, revealed significant
      interactions with regions of cerebellar lobule VII from seeds both in the right
      pSTS and right SPL, such that activity in these sites was more highly correlated
      during imitation. A similar interaction was found between right pSTS and left
      IPL. These results clarify the role of cortical regions supporting action
      observation, action execution and imitation, and highlight the role the
      cerebellum may play in facilitating both motor and nonmotor aspects of imitation.

PMID- 21958652
TI  - Cutaneous and mucosal mucormycosis mimicking pancreatic panniculitis and gouty
      panniculitis.
AB  - BACKGROUND: Histopathologic study of lesions of cutaneous mucormycosis usually
      shows suppurative granulomas involving the deep dermis and subcutaneous fat.
      Large, broad and non-septate fungal hyphae are easily identified within the
      necrotic areas. OBJECTIVE: The main goal of our study is to describe the
      histopathologic features of 13 cases of cutaneo-mucous mucormycosis, which
      mimicked the findings of pancreatic and/or gouty panniculitis and discuss the
      histopathologic differential diagnosis among these 3 disorders. METHODS:
      Histopathologic examination of sections stained with hematoxylin-eosin, periodic
      acid-Schiff (PAS), Gomori methenamine, and Grocott stains. All sections were
      examined under polarized light. One case was immunohistochemically studied with
      anti-BCG antibody. RESULTS: Histopathologically, the most striking feature
      consisted of the presence of groups of necrotic adipocytes lacking nuclei and
      large cytoplasm with pale basophilic hue due to calcium salts deposition. In
      other areas, groups of necrotic adipocytes filled with radially oriented needle
      shaped and slightly eosinophilic crystals were seen. These intracellular crystals
      were refractile under polarized light examination. Numerous thick-walled non
      septate fungal hyphae scattered throughout the necrotic areas were also seen in
      all cases. LIMITATIONS: The study was limited to 13 cases. CONCLUSIONS:
      Histopathologic study of 13 cases of subcutaneous mucormycosis demonstrated
      features closely resembling those of pancreatic panniculitis and/or gouty
      panniculitis. Ghost adipocytes should be not considered as diagnostic of
      pancreatic panniculitis and necrotic adipocytes containing needle-shaped
      refractile crystals should be not interpreted as specific of gouty panniculitis.

PMID- 21958653
TI  - Preclinical multimodality phantom design for quality assurance of tumor size
      measurement.
AB  - BACKGROUND: Evaluation of changes in tumor size from images acquired by
      ultrasound (US), computed tomography (CT) or magnetic resonance imaging (MRI) is
      a common measure of cancer chemotherapy efficacy. Tumor size measurement based on
      either the World Health Organization (WHO) criteria or the Response Evaluation
      Criteria in Solid Tumors (RECIST) is the only imaging biomarker for anti-cancer
      drug testing presently approved by the United States Food and Drug Administration
      (FDA). The aim of this paper was to design and test a quality assurance phantom
      with the capability of monitoring tumor size changes with multiple preclinical
      imaging scanners (US, CT and MRI) in order to facilitate preclinical anti-cancer
      drug testing. METHODS: Three phantoms (Gammex/UTHSCSA Mark 1, Gammex/UTHSCSA Mark
      2 and UTHSCSA multimodality tumor measurement phantom) containing tumor
      simulating test objects were designed and constructed. All three phantoms were
      scanned in US, CT and MRI devices. The size of test objects in the phantoms was
      measured from the US, CT and MRI images. RECIST, WHO and volume analyses were
      performed. RESULTS: The smaller phantom size, simplified design and better test
      object CT contrast of the UTHSCSA multimodality tumor measurement phantom allowed
      scanning of the phantom in preclinical US, CT and MRI scanners compared with only
      limited preclinical scanning capability of Mark 1 and Mark 2 phantoms. For all
      imaging modalities, RECIST and WHO errors were reduced for UTHSCSA multimodality
      tumor measurement phantom (<=1.69 +/- 0.33%) compared with both Mark 1 (<= -7.56
      +/- 6.52%) and Mark 2 (<= 5.66 +/- 1.41%) phantoms. For the UTHSCSA multimodality
      tumor measurement phantom, measured tumor volumes were highly correlated with
      NIST traceable design volumes for US (R2 = 1.000, p < 0.0001), CT (R2 = 0.9999, p
      < 0.0001) and MRI (R2 = 0.9998, p < 0.0001). CONCLUSIONS: The UTHSCSA
      multimodality tumor measurement phantom described in this study can potentially
      be a useful quality assurance tool for verifying radiologic assessment of tumor
      size change during preclinical anti-cancer therapy testing with multiple imaging
      modalities.

PMID- 21958654
TI  - Comments regarding 'Correlations between clinical variables and gene-expression
      profiles in carotid plaque instability'.

PMID- 21958655
TI  - Evoked-potential changes following discrimination learning involving complex
      sounds.
AB  - OBJECTIVE: Perceptual sensitivities are malleable via learning, even in adults.
      We trained adults to discriminate complex sounds (periodic, frequency-modulated
      sweep trains) using two different training procedures, and used psychoacoustic
      tests and evoked potential measures (the N1-P2 complex) to assess changes in both
      perceptual and neural sensitivities. METHODS: Training took place either on a
      single day, or daily across eight days, and involved discrimination of pairs of
      stimuli using a single-interval, forced-choice task. In some participants,
      training started with dissimilar pairs that became progressively more similar
      across sessions, whereas in others training was constant, involving only one,
      highly similar, stimulus pair. RESULTS: Participants were better able to
      discriminate the complex sounds after training, particularly after progressive
      training, and the evoked potentials elicited by some of the sounds increased in
      amplitude following training. Significant amplitude changes were restricted to
      the P2 peak. CONCLUSIONS: Our findings indicate that changes in perceptual
      sensitivities parallel enhanced neural processing. SIGNIFICANCE: These results
      are consistent with the proposal that changes in perceptual abilities arise from
      the brain's capacity to adaptively modify cortical representations of sensory
      stimuli, and that different training regimens can lead to differences in cortical
      sensitivities, even after relatively short periods of training.

PMID- 21958656
TI  - EEG in the emergency department: speeding the patients toward the right treatment
      plans.

PMID- 21958657
TI  - Explicit semantic tasks are necessary to study semantic priming effects with high
      rates of repetition.
AB  - OBJECTIVE: The purpose of the present study was to clarify in which experimental
      conditions the semantic processing of repeated words is preserved. METHODS: We
      contrasted a short (250 ms) and a long (1000 ms) stimulus onset asynchrony (SOA)
      in two different experiments, using a relatively low proportion of related words
      (30%). One group of participants performed a lexical decision task (LDT) and a
      second group performed an explicit semantic matching task with the same words
      (except for pseudowords) and the same task parameters. In both tasks, word
      stimuli consisted solely of two prime and two target words repeated throughout
      the experiment. RESULTS: The effects of semantic priming on reaction time (RT)
      and the amplitude of the N400 ERP were absent for both the short and the long SOA
      in the LDT. In contrast, in the explicit semantic task, these effects were
      significant. In this task, the activity of N400 generators in the left superior
      temporal gyrus and the inferior parietal cortex significantly differentiated
      primed and unprimed trials but this effect did not interact with SOA.
      CONCLUSIONS: Our results indicate that task instruction is critical to preserve
      semantic processing with repeated presentations. SIGNIFICANCE: Using explicit
      semantic designs, it may be possible to study associative or categorical
      relations between individual concepts.

PMID- 21958658
TI  - Auditory and visual cortical activity during selective attention in fragile X
      syndrome: a cascade of processing deficiencies.
AB  - OBJECTIVE: This study examined whether attention deficits in fragile X syndrome
      (FXS) can be traced back to abnormalities in basic information processing.
      METHOD: Sixteen males with FXS and 22 age-matched control participants (mean age
      29 years) performed a standard oddball task to examine selective attention in
      both auditory and visual modalities. Five FXS males were excluded from analysis
      because they performed below chance level on the auditory task. ERPs were
      recorded to investigate the N1, P2, N2b, and P3b components. RESULTS: N1 and N2b
      components were significantly enhanced in FXS males to both auditory and visual
      stimuli. Interestingly, in FXS males, the P3b to auditory stimuli was
      significantly reduced relative to visual stimuli. These modality differences in
      information processing corresponded to behavioral results, showing more errors on
      the auditory than on the visual task. CONCLUSIONS: The current findings suggest
      that attentional impairments in FXS at the behavioral level can be traced back to
      abnormalities in event-related cortical activity. These information processing
      abnormalities in FXS may hinder the allocation of attentional resources needed
      for optimal processing at higher-levels. SIGNIFICANCE: These findings demonstrate
      that auditory information processing in FXS males is critically impaired relative
      to visual information processing.

PMID- 21958659
TI  - [Arbovirus diseases extension: who is guilty?].

PMID- 21958660
TI  - Occurrence and severity of concomitant injuries in other areas than the face in
      children with mandibular and midfacial fractures.
AB  - PURPOSE: To clarify the occurrence, causes, severity, and predictors of
      concomitant injuries in pediatric patients with facial fractures. PATIENTS AND
      METHODS: Files of 339 pediatric patients who had sustained facial fractures at
      age 15 years or younger were reviewed. Outcome variables were injured organ
      systems other than the face, types of injuries in areas other than the face, and
      severity of injuries in areas other than the face. Explanatory variables were
      gender, age, mechanism of trauma, and type of facial fracture. RESULTS:
      Concomitant injuries in organ systems other than the face were observed in 11.0%.
      Limb injuries occurred in 9.1%, head and neck injuries in 5.6%, and chest
      injuries in 1.8%. The most common injury types were upper limb injury (8.0%),
      brain injury (3.2%), and lower limb injury (2.9%). Severe head and neck injuries
      occurred in 3.5% and severe chest injuries in 1.2%. Concomitant injuries occurred
      more frequently after motor vehicle accidents and falls from height compared with
      other etiologies (P < .001) and more frequently in association with combined
      mandibular and midfacial fractures than in association with other fracture types
      (P < .001). CONCLUSIONS: Concomitant injuries in areas other than the face should
      be expected first and foremost after high-speed trauma mechanisms and in
      association with severe facial fractures. Concomitant injuries in general occur
      most frequently in the limbs, with severe concomitant injuries in particular
      occurring most often in the head and neck region and chest, emphasizing the
      importance of multiprofessional teamwork in the diagnosis of pediatric patients
      who have sustained facial fractures.

PMID- 21958661
TI  - Unilateral stellate ganglion block produces bidirectional changes in tissue
      oxygen tension of the mental nerve in rabbits.
AB  - PURPOSE: The purpose of this study was to investigate changes in the tissue
      oxygen tension (PO(2)) of the mental nerve bilaterally before and after
      unilateral stellate ganglion block (SGB). MATERIALS AND METHODS: Nine male Japan
      white rabbits were used. Anesthesia was maintained by a continuous infusion of
      propofol under mechanical ventilation with room air. For the SGB, the tip of a 26
      gauge needle was placed on the left transverse process of the cervical vertebra;
      0.2 mL of 1% lidocaine solution was injected. Data were recorded immediately
      before SGB and when the maximal change in PO(2) after SGB was observed. Observed
      variables were heart rate, blood pressure, common carotid arterial blood flow,
      tongue mucosal blood flow, left PO(2), and right PO(2). RESULTS: PO(2) showed
      maximal changes 7.9 +/- 2.0 minutes after SGB. No changes were observed in heart
      rate and blood pressure after SGB. Common carotid arterial blood flow, tongue
      mucosal blood flow, and left PO(2) were increased by 106.4% +/- 39.8%, 36.2% +/-
      35.2%, and 38.7% +/- 19.8%, respectively, after SGB. In contrast, right PO(2) was
      decreased by 29.8% +/- 7.4% after SGB. CONCLUSIONS: These results suggest that
      unilateral SGB produces bidirectional changes in the PO(2) of the mental nerve
      and that SGB decreases the PO(2) of the mental nerve on the contralateral side.

PMID- 21958662
TI  - Soft tissue changes from maxillary distraction osteogenesis versus orthognathic
      surgery in patients with cleft lip and palate--a randomized controlled clinical
      trial.
AB  - PURPOSE: The objective of this randomized controlled clinical trial was to
      compare the soft tissue changes after maxillary advancement using conventional
      orthognathic surgery (CO) and distraction osteogenesis (DO) in patients with
      cleft lip and palate (CLP). MATERIALS AND METHODS: The study group of 39 CLP
      patients with maxillary hypoplasia underwent either CO or DO with 4 to 10 mm of
      maxillary advancement. Lateral cephalographs were taken preoperatively and
      postoperatively at regular intervals. A series of skeletal, dental, and soft
      tissue landmarks was used to evaluate the changes in the soft tissue and the
      correlation of hard and soft tissue changes and ratios. RESULTS: Significant
      differences were found between the CO and DO patients at A point in both
      maxillary advancement and downgrafting in the early follow-up period. On soft
      tissue landmarks of pronasale, subnasale, and labial superius, significant
      differences were found between the 2 groups at 6 months postoperatively only with
      maxillary advancement. There was better correlation of hard and soft tissue
      changes with maxillary advancement. The nasal projection was significantly
      different between the 2 groups at the early and intermediate period. There was
      much more consistent hard to soft tissue ratios in maxillary advancement with DO
      than with CO. CONCLUSIONS: Both CO and DO can induce significant soft tissue
      changes of the upper lip and nose, particularly with maxillary advancement. DO
      generates more consistent hard to soft tissue ratios.

PMID- 21958664
TI  - Myofibroma of the mandible in an infant: case report, review of the literature,
      and discussion.

PMID- 21958663
TI  - Prevalence of third molars with caries experience or periodontal pathology in
      young adults.
AB  - PURPOSE: We assessed the prevalence of caries experience and periodontal
      pathology on asymptomatic third molars in young adults. SUBJECTS AND METHODS:
      Healthy subjects with 4 asymptomatic third molars were enrolled in an
      institutional review board-approved study during a 5-year period. Full mouth
      periodontal probing, 6 sites per tooth, was the measure of clinical periodontal
      status. The presence or absence of occlusal caries experience (carious lesions or
      restorations, including sealants) on third molars and on any surface of the first
      and second molars were assessed using a visual-tactile examination and panoramic
      radiographs. The primary outcome measures were at least 1 periodontal probing
      depth of at least 4 mm versus none and caries experience versus no caries
      experience. RESULTS: The data were analyzed from 409 subjects, who averaged 25
      years old. More subjects were female (53%) and white (76%). More subjects had at
      least 1 periodontal probing depth of 4 mm or deeper on a third molar (55%) than
      on the distal of a second molar (46%). These findings were more likely to be
      detected around a third molar in subjects with all third molars at the occlusal
      plane (72%) than in subjects with at least one third molar below (33%). Overall,
      fewer subjects were affected by third molar caries experience than first or
      second molars (24% vs 73%, respectively). Of the subset of subjects with all four
      third molars at the occlusal plane, 26% were affected by both third molar
      periodontal pathology and caries experience and 16% were caries and periodontal
      pathology free. CONCLUSIONS: In these cross-sectional analyses, periodontal
      pathology was detected more frequently on third molars than on first and second
      molars and caries experience was detected more frequently on first and second
      molars than on third molars.

PMID- 21958665
TI  - Smoking as a significant risk factor for infections after orthognathic surgery.
AB  - PURPOSE: This study was conducted to determine risk factors for infections after
      orthognathic surgery. PATIENTS AND METHODS: This was a retrospective cohort
      study, including files of patients who had undergone 1-jaw orthognathic surgery
      (ie, bilateral sagittal split osteotomy or Le Fort I osteotomy) during a 7-year
      period. The outcome variable was surgical site infection. Predictor variables
      were age, gender, general disease, smoking habit, site of orthognathic surgery,
      duration of operation, type of osteosynthesis material, and use of postoperative
      drainage. Data analysis was performed with chi(2) test and logistic regression
      analysis. RESULTS: In total 286 patients met the inclusion criteria (174 women,
      60.8%). Patients' age range was 17 to 56.5 years (average, 34.8 years). The
      infection rate was 9.1%. The only statistically significant risk factor for
      infection was smoking. CONCLUSIONS: The results emphasize the importance of
      preoperative patient information about smoking. Orthognathic surgery, because of
      the long orthodontic preoperative treatment period, provides a good opportunity
      to encourage and assist patients to cease smoking and thus avoid an increased
      risk for postoperative infections.

PMID- 21958667
TI  - Caveolin-1 hydrophobic segment peptides insertion into membrane mimetic systems:
      role of proline residue.
AB  - Caveolin-1 has a segment of hydrophobic amino acids comprising approximately
      residues 103-122 that are anchored to the membrane with cholesterol-rich domains.
      Previously, we reported that changing the Pro(110) residue to Ala (the P110A
      mutant) prevents not only the localization of the protein into lipid rafts but
      also the formation and functioning of caveolae. The conformational state of
      caveolin-1 can be shifted toward the transmembrane arrangement by this single
      amino acid mutation. To model the conformation, and extent of membrane insertion
      of this segment into membrane-mimetic environments, we have prepared a peptide
      corresponding to this hydrophobic segment of caveolin-1 having the sequence
      KKKKLSTIFGIPMALIWGIYFAILKKKKK-amide and the mutated version,
      KKKKLSTIFGIAMALIWGIYFAILKKKKK-amide. These peptides contain flanking Lys residues
      to facilitate purification and handling of the peptide. Circular dichroism
      measurements demonstrated that the mutated peptide has increased helical content
      compared with the wild type both in the presence and absence of lipid. The
      fluorescence emission from the Trp residues in the peptide showed significant
      blue shifts in the presence of liposomes, however the presence of cholesterol in
      hydrated vesicle bilayers decreases its helical content. Our overall findings
      support our studies with the intact protein in cells and suggest that the peptide
      of WT caveolin-1 hydrophobic segment has an intrinsic preference not to maintain
      its conformation as a rigid transmembrane helix. Substituting the Pro residue
      with an Ala allows the peptide to exist in a more hydrophobic environment likely
      as a consequence of a change in its conformation to a straight hydrophobic helix
      that traverses the membrane.

PMID- 21958668
TI  - A consensus segment in the M2 domain of the hP2X(7) receptor shows ion channel
      activity in planar lipid bilayers and in biological membranes.
AB  - The P2X(7) receptor (P2X(7)R) is an ATP-gated, cation-selective channel permeable
      to Na(+), K(+) and Ca(2+). This channel has also been associated with the opening
      of a non-selective pore that allows the flow of large organic ions. However, the
      biophysical properties of the P2X(7)R have yet to be characterized unequivocally.
      We investigated a region named ADSEG, which is conserved among all subtypes of
      P2X receptors (P2XRs). It is located in the M2 domain of hP2X(7)R, which aligns
      with the H5 signature sequence of potassium channels. We investigated the channel
      forming ability of ADSEG in artificial planar lipid bilayers and in biological
      membranes using the cell-attached patch-clamp techniques. ADSEG forms channels,
      which exhibit a preference for cations. They are voltage independent and show
      long-term stability in planar lipid bilayers as well as under patch-clamping
      conditions. The open probability of the ADSEG was similar to that of native
      P2X(7)R. The conserved part of the M2 domain of P2X(7)R forms ionic channels in
      planar lipid bilayers and in biological membranes. Its electrophysiological
      characteristics are similar to those of the whole receptor. Conserved and
      hydrophobic part of the M2 domain forms ion channels.

PMID- 21958666
TI  - Structural correlates of selectivity and inactivation in potassium channels.
AB  - Potassium channels are involved in a tremendously diverse range of physiological
      applications requiring distinctly different functional properties. Not
      surprisingly, the amino acid sequences for these proteins are diverse as well,
      except for the region that has been ordained the "selectivity filter". The goal
      of this review is to examine our current understanding of the role of the
      selectivity filter and regions adjacent to it in specifying selectivity as well
      as its role in gating/inactivation and possible mechanisms by which these
      processes are coupled. Our working hypothesis is that an amino acid network
      behind the filter modulates selectivity in channels with the same signature
      sequence while at the same time affecting channel inactivation properties. This
      article is part of a Special Issue entitled: Membrane protein structure and
      function.

PMID- 21958669
TI  - Studies on neutral, cationic and biotinylated cationic microbubbles in enhancing
      ultrasound-mediated gene delivery in vitro and in vivo.
AB  - Ultrasound-mediated gene transfer is emerging as a practical means of
      facilitating targeted gene expression and is significantly enhanced in the
      presence of exogenously added microbubbles. This study explores the influence of
      microbubble surface modifications on their interaction with plasmid DNA and
      target cells, and the functional consequences of those interactions in terms of
      ultrasound-mediated gene transfer. Polyethylene glycol-stabilized, lipid-shelled
      microbubbles with neutral (SDM201), cationic (SDM202) and biotinylated cationic
      (SDM302) surfaces were compared in terms of their abilities to interact with a
      luciferase-encoding reporter plasmid DNA and with target cells in vitro. The
      results demonstrate that the biotinylated cationic microbubble>cationic
      microbubble>neutral microbubble, in terms of their abilities to interact with
      target cells and to enhance ultrasound-mediated gene transfer, particularly at
      low microbubble concentration. The presence of a net positive charge on both
      cationic microbubbles promoted the formation of microbubble-nucleic acid
      complexes, although preformation of the complexes prior to addition to target
      cells inhibited the interaction between the microbubbles and target cells in
      vitro. The impact of these findings on potential in vitro or ex vivo therapeutic
      applications of microbubble-enhanced ultrasound-mediated gene transfer is
      discussed. All three microbubble preparations could be used to facilitate gene
      transfer in vivo and the potential advantages associated with the use of the
      cationic microbubbles for targeted gene delivery are discussed.

PMID- 21958670
TI  - Vascular obstruction at the level of the ankle joint as a complication of hip
      arthroscopy.
AB  - We report a case of foot vascular obstruction as a complication of hip
      arthroscopy. A 23-year-old female patient underwent hip arthroscopy for
      femoroacetabular impingement. The duration of the procedure was 80 minutes,
      including 20 minutes with traction for arthroscopy of the central compartment and
      60 minutes without traction for cam treatment in the peripheral compartment.
      Three days postoperatively, the patient complained of a cold foot and pain and
      paresthesia during leg and foot elevation with continuous passive motion therapy.
      With persisting symptoms, she was seen by the referring physician 4 days
      postoperatively. Pulselessness at the level of the ankle and reduced capillary
      perfusion were observed. Doppler sonography and magnetic resonance angiography
      showed an occlusion of the peroneal, posterior tibial, and anterior tibial
      arteries at the level of the right ankle. The patient was readmitted to the
      hospital and underwent intravenous prostaglandin E1 therapy for 9 days, followed
      by oral clopidogrel treatment for 6 weeks. After 8 weeks, follow-up Doppler
      sonographic findings were normal. Subjective paresthesia and sensation of
      coldness resolved completely after 6 months. Possible theories for this
      complication and strategies on how to avoid it are discussed.

PMID- 21958671
TI  - All-arthroscopic biologic total shoulder resurfacing.
AB  - The treatment of advanced, bipolar glenohumeral osteoarthritis in the young
      patient is particularly challenging because of the expected failure of a
      traditional shoulder arthroplasty within the patient's lifetime. We have had
      early success performing osteochondral allograft resurfacing of the humeral head
      articular surface and glenoid articular surface, and we describe a new all
      arthroscopic technique for performing this procedure. In the context of our new
      procedure, we have reviewed the available literature on the topic of biologic
      resurfacing with osteochondral allograft and have provided an overview of the
      relevant findings. Although only short-term follow-up data are available, our
      results in young patients have been promising in terms of regained motion,
      minimal pain, and accelerated rehabilitation. We believe that this new
      arthroscopic biologic shoulder resurfacing technique has the potential to be
      superior to other available treatments for this patient population because it
      preserves bone stock, limits damage to surrounding structures, and allows for
      early rehabilitation. Although longer-term follow-up is needed, early results
      have been greatly encouraging.

PMID- 21958672
TI  - Magnetic resonance imaging evaluation of knee kinematics after anterior cruciate
      ligament reconstruction with anteromedial and transtibial femoral tunnel drilling
      techniques.
AB  - PURPOSE: The purpose of this study was to use magnetic resonance (MR) imaging to
      evaluate the translational and rotational kinematics of anterior cruciate
      ligament (ACL) reconstructed knees with transtibial (TT) and anteromedial (AM)
      femoral tunnel drilling. METHODS: ACL reconstruction was performed in 21
      subjects: 12 with AM drilling (5 men and 7 women; mean age, 33 +/- 9 years;
      imaged 18 +/- 5 months after surgery) and 9 with TT drilling (5 men and 4 women;
      mean age, 32 +/- 9 years; imaged 12 +/- 8 months after surgery). Three-tesla MR
      imaging was obtained bilaterally at extension and 30 degrees  to 40 degrees  of
      flexion under simulated loading (125 N). MR images were segmented and kinematic
      calculations done with in-house MATLAB software (The MathWorks, Natick, MA).
      Translation and rotation of the tibia and the tibiofemoral contact area were
      measured. Statistical analysis treated reconstructed and contralateral knees as
      independent groups. Reconstructed groups were compared with analysis of
      covariance using contralateral knees as baseline. P < .05 indicated significance.
      RESULTS: All kinematic measures in the AM group were similar to contralateral
      knees. The TT group showed significantly more total tibial rotation than
      contralateral knees (TT, 8.4 degrees  +/- 3.9 degrees ; contralateral, 2.9
      degrees  +/- 6.8 degrees ) (P = .03), whereas the AM group did not (AM, 3.1
      degrees  +/- 5.6 degrees ; contralateral, 2.3 degrees  +/- 5.4 degrees ) (P =
      .36). At knee extension, the tibia was more externally rotated in the TT group
      than in controls. Medial tibial translation was greater in the TT group than in
      controls. The AM group showed increased contact area in the lateral compartment
      compared with controls; no differences were seen in the TT group. CONCLUSIONS:
      Using an MR-based approach, we found that knee kinematics were better restored
      with the AM femoral tunnel drilling ACL reconstruction than with the TT femoral
      tunnel drilling approach, which resulted in increased knee laxity. Our in vivo
      results support previous cadaveric and clinical studies that have found AM ACL
      reconstruction to restore anatomy and stability better than the TT approach.
      However, the clinical significance of increased contact area in the AM group
      remains unclear. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

PMID- 21958673
TI  - Bone health management in patients with breast cancer: current standards and
      emerging strategies.
AB  - In women who develop bone metastases from breast cancer (BC), interactions
      between tumor cells and osteoclasts within the bone lead to localized bone
      destruction and increase the risk of skeletal-related events (SREs).
      Bisphosphonates inhibit osteoclast-mediated bone resorption, and have been used
      extensively for treating post-menopausal osteoporosis and reducing the risk of
      SREs in patients with bone metastases. A number of clinical trials in women with
      early stage BC have demonstrated that adding bisphosphonates to adjuvant
      endocrine therapy can prevent bone loss and may prevent disease recurrence and
      improve disease-free survival. In women with bone metastases from BC,
      bisphosphonates have demonstrated efficacy for reducing skeletal morbidity and
      pain and improving quality of life. Recent economic analyses have demonstrated
      that bisphosphonate therapy is a cost-effective use of healthcare resources. This
      review summarizes the available data for bisphosphonate benefits in both the
      adjuvant and metastatic settings in the context of evolving clinical practice.

PMID- 21958674
TI  - Social networks and implementation of evidence-based practices in public youth
      serving systems: a mixed-methods study.
AB  - BACKGROUND: The present study examines the structure and operation of social
      networks of information and advice and their role in making decisions as to
      whether to adopt new evidence-based practices (EBPs) among agency directors and
      other program professionals in 12 California counties participating in a large
      randomized controlled trial. METHODS: Interviews were conducted with 38
      directors, assistant directors, and program managers of county probation, mental
      health, and child welfare departments. Grounded-theory analytic methods were used
      to identify themes related to EBP adoption and network influences. A web-based
      survey collected additional quantitative information on members of information
      and advice networks of study participants. A mixed-methods approach to data
      analysis was used to create a sociometric data set (n = 176) for examination of
      associations between advice seeking and network structure. RESULTS: Systems
      leaders develop and maintain networks of information and advice based on roles,
      responsibility, geography, and friendship ties. Networks expose leaders to
      information about EBPs and opportunities to adopt EBPs; they also influence
      decisions to adopt EBPs. Individuals in counties at the same stage of
      implementation accounted for 83% of all network ties. Networks in counties that
      decided not to implement a specific EBP had no extra-county ties. Implementation
      of EBPs at the two-year follow-up was associated with the size of county, urban
      versus rural counties, and in-degree centrality. Collaboration was viewed as
      critical to implementing EBPs, especially in small, rural counties where agencies
      have limited resources on their own. CONCLUSIONS: Successful implementation of
      EBPs requires consideration and utilization of existing social networks of high
      status systems leaders that often cut across service organizations and their
      geographic jurisdictions. TRIAL REGISTRATION: NCT00880126.

PMID- 21958675
TI  - [Predictive ability of the CT to evaluate cervical lymph nodes in head and neck
      tumours].
AB  - OBJECTIVE: The aim of this study was to determine the predictive value of
      computed tomography (CT) i.e., its sensitivity and specificity in detecting
      metastatic lymph nodes of head and neck tumours. We also studied the capacity of
      CT in correct nodal staging. PATIENTS AND METHODS: A CT was performed on 95
      patients diagnosed with neoplastic disease of the pharynx and/or larynx. All
      patients subsequently underwent cervical lymph node dissections. In the imaging
      study, the following parameters were considered for suspected radiological nodal
      involvement: lymph node diameter greater than 10mm, lesion margins poorly
      defined, capsule enhancement after contrast administration and lymph nodes that,
      despite their size, had signs of central necrosis. RESULTS: In the dissections,
      70.53% resulted N+ in the histological study. The sensitivity of CT was 82.09%
      and the specificity, 85.71%. The CT detected positivity in 55 of the 67
      histologically pathological dissections, while the CT detected negativity in 24
      of the 28 dissections histologically negative. The weighted kappa index value was
      0.6408, indicating limited capacity for appropriate staging of the lymph nodes.
      CONCLUSIONS: While the ability of CT to detect metastatic lymph nodes in head and
      neck tumours is quite acceptable, it is less so for correctly staging them. It is
      therefore necessary to look for other imaging tests that provide greater accuracy
      to avoid unnecessary elective neck dissections and to reduce morbidity and
      mortality from them. We must now pay attention to new imaging techniques such as
      PET and PET/CT.

PMID- 21958676
TI  - [Internal carotid artery parallel to the skull base].

PMID- 21958677
TI  - Antiproteinuric treatment reduces urinary loss of vitamin D-binding protein but
      does not affect vitamin D status in patients with chronic kidney disease.
AB  - Vitamin D deficiency is common in chronic kidney disease (CKD). Increased urinary
      loss of vitamin D binding protein (VDBP), the main transporter of 25
      hydroxyvitamin D(3) in the circulation, has been postulated to contribute to
      vitamin D deficiency in proteinuria. To test this hypothesis we analyzed urinary
      and plasma levels of VDBP, 25-hydroxyvitamin D(3) and 1,25-dihydroxyvitamin D(3)
      from proteinuric patients, before and after antiproteinuric interventions. We
      performed a post-hoc analysis of a clinical trial in CKD patients (n=13,
      creatinine clearance median 60 (range 25-177) ml/min) subjected to the following
      study periods: washout (no antiproteinuric treatment, 4 weeks), lisinopril 40mg
      QD (ACEi, 6 weeks), or indomethacin 75mg BID (NSAID, 4 weeks) in randomized
      sequence. Healthy subjects screened for donation (n=10) served as controls.
      Plasma and urine VDBP levels were measured by ELISA, 25-hydroxyvitamin D(3)
      levels by LC-MS and 1,25-dihydroxyvitamin D(3) levels by radioimmunoassay. In CKD
      patients urinary VDBP excretion was strongly increased (median (range) 5413 (155
      211,027) MUg/24h) as compared to healthy controls (64 (23-111) MUg/24h, p<0.001).
      Both NSAID and ACEi significantly decreased urinary VDBP excretion, in proportion
      to proteinuria reduction. Plasma VDBP, 25-hydroxyvitamin D(3) and 1,25
      dihydroxyvitamin D(3) levels, however, were similar between patients and controls
      and not affected by antiproteinuric intervention. Urinary VDBP excretion is
      markedly increased in proteinuria and responds to antiproteinuric treatment.
      Urinary VDBP loss is not associated with plasma VDBP or vitamin D(3) levels,
      suggesting that urinary loss of VDBP does not affect vitamin D status.

PMID- 21958678
TI  - Relationship between hepatic haemodynamics assessed by Doppler ultrasound and
      liver stiffness.
AB  - AIM: We tested the relationship between hepatic haemodynamics assessed by Doppler
      ultrasonography and liver stiffness assessed by Transient Elastography in
      hepatitis C related chronic liver disease. METHODS: Three liver Doppler
      ultrasound parameters (hepatic artery resistance index, splenic artery resistance
      index and waveform pattern in hepatic veins) and liver stiffness measured by
      Transient Elastography were analysed in one hundred consecutive patients affected
      by hepatitis C related chronic liver disease. RESULTS: Hepatic and splenic
      arteries resistance indexes correlate significantly (p<0.0001 for both) with
      liver stiffness. A hepatic artery resistance index cut-off value of 0.64 provided
      sensitivity and specificity respectively of 84.4% and 69.1% for predicting liver
      stiffness <=or >13 kPa, whereas a splenic artery resistance index cut-off value
      of 0.56 provided sensitivity and specificity respectively of 81.3% and 48.5%. The
      coincidental finding of both resistance indexes above the respective cut-off
      values showed a good accuracy in identifying patients with liver stiffness values
      >13 kPa (accuracy=78%, +LR=2.90, -LR=0.31). A significant difference in liver
      stiffness values was evident between patients with triphasic and bi- or
      monophasic waveform pattern (p=0.005). CONCLUSIONS: Hepatic and splenic arteries
      resistance indexes and the hepatic veins waveform pattern assessed by Doppler
      ultrasound may provide information similar to that of Transient Elastography in
      hepatitis C related chronic liver disease.

PMID- 21958680
TI  - Height in adolescence predicts polydrug use in adolescence and young adulthood.
AB  - Prior research has noted a relationship between an individual's height in
      adolescence and their personality development later in life. This study examined
      whether height in adolescence--net of possible confounding variables such as age
      and biological maturity--predicted polydrug use in adolescence and young
      adulthood. The results revealed a positive and statistically significant
      association, wherein taller youths were more likely to report using an array of
      drugs. Supplemental analyses indicated that the relationship is not specific to
      males as some theories would suggest. Possible mediating mechanisms such as
      exposure to drug-using peers, self-control, depression, and self-esteem are
      considered. Implications of the findings are discussed.

PMID- 21958681
TI  - Lead levels in umbilical cord blood in Belgium: a cross-sectional study in five
      maternity units.
AB  - The average blood lead concentration has significantly decreased over the last
      two decades among the general population. However, in Belgium, there are still
      high-risk populations such as groups of pregnant women who have shown elevated
      lead levels. The objective of this study was to evaluate the current situation of
      lead cord blood levels and identify sources of lead exposure by a questionnaire
      survey. The study was conducted in 5 maternity units in Belgium; for each,
      umbilical cord blood samples were collected from 50 consecutive births. At the
      same time a questionnaire on possible sources of lead exposure was administered
      to the mother. The dependent variable was a dichotomous lead level variable (<20
      MUg/L vs. >= 20 MUg/L). The factors associated with elevated lead levels (>= 20
      MUg/L) were mother's country of origin from south Mediterranean and from Sub
      Saharan Africa, mother's educational level, using 'tagine' plates for cooking and
      using khol for make-up, but, after adjusting for potential confounding factors,
      only the mother's country origin from south Mediterranean (adjusted odds ratio,
      5.51; 95% confidence interval [CI], 1.68-18.08; p=0.005) and from Sub-Saharan
      Africa (adjusted odds ratio, 8.14; 95% CI, 2.26-29.40; p=0.001) were
      significantly associated with elevated cord blood lead concentrations (>= 20
      MUg/L). The results of this study are similar to those found by a previous study
      in Belgium in 2004. Sources of exposure are difficult to distinguish with this
      questionnaire, which might be due to other important sources of exposure that
      were not included in the questionnaire. Confirmation of these risk factors in
      future studies could lead to new prevention strategies for populations who are at
      risk for subsequent lead exposure.

PMID- 21958679
TI  - Developmental exposure to a serotonin agonist produces subsequent behavioral and
      neurochemical changes in the adult male prairie vole.
AB  - Autistic spectrum disorders (ASDs) are classified as pervasive developmental
      disorders characterized by abnormalities in various cognitive and behavioral
      functions. Although exact underlying causes are still unknown, nearly 30% of
      autistic patients show elevated blood levels of serotonin (5-HT) and, therefore,
      various genetic and environmental factors that are known to elevate 5-HT levels
      may play a role in the development of ASDs. In the present study, we used the
      socially monogamous male prairie vole (Microtus ochrogaster) as an animal model
      to examine the effects of perinatal exposure to 5-methoxytryptamine (5-MT), a non
      selective serotonin agonist, on subsequent behavioral and neurochemical changes
      in the brain. 5-MT treated males showed a decrease in affiliation and an increase
      in anxiety-related behavior, as well as a decrease in the density of 5-HT
      immunoreactive (ir) fibers in the amygdala and oxytocin-ir and vasopressin-ir
      cells in the paraventricular nucleus of the hypothalamus, compared to saline
      treated controls. These data indicate that exposure to 5-HT during early
      development can induce abnormalities in various neurochemical systems which, in
      turn, may underlie deficits in social and anxiety-related behaviors. In addition,
      these data will help to establish the prairie vole model to study the
      neurobiological underpinnings of complex neuropsychiatric disorders such as ASDs.

PMID- 21958682
TI  - Endocrine disrupting chemicals in urine of Japanese male partners of subfertile
      couples: a pilot study on exposure and semen quality.
AB  - The concentrations of chemicals with suspected endocrine disrupting effect were
      measured in urine samples collected from 42 Japanese male partners of couples who
      had infertility consultation at a gynecology clinic in Tokyo. The urinary
      analytes included metabolites of 5 phthalate diesters, pyrethroid insecticide (3
      phenoxybenzoic acid, 3-PBA) and soy isoflavones (daidzein and equol), and
      cadmium. The semen parameters (semen volume, concentration and motility) of the
      male subjects were examined at the clinic as a diagnostic screening. Multiple
      regression analysis using one of the semen parameters examined as dependent
      variable and urinary biomarkers with age, body mass index, abstinent period,
      alcohol drinking, smoking and consumption frequency of selected foods as
      independent variables. For sperm concentration, urinary mono-n-butyl phthalate
      was selected as a significant independent variable with positive beta, while
      urinary daidzein was with negative beta. Consumption frequency of coffee
      (negative) and fruits (positive) were also significant. For sperm motility,
      urinary 3-PBA was selected as significant with negative beta as well as
      detectability of equol and frequency of coffee consumption with negative beta
      while smoking was with positive beta. This pilot study suggested the pyrethroid
      exposure level and dietary habit (coffee and soy products) as a significant
      contributor to poorer semen quality.

PMID- 21958683
TI  - Incorporating expert knowledge when learning Bayesian network structure: a
      medical case study.
AB  - OBJECTIVES: Bayesian networks (BNs) are rapidly becoming a leading technology in
      applied Artificial Intelligence, with many applications in medicine. Both
      automated learning of BNs and expert elicitation have been used to build these
      networks, but the potentially more useful combination of these two methods
      remains underexplored. In this paper we examine a number of approaches to their
      combination when learning structure and present new techniques for assessing
      their results. METHODS AND MATERIALS: Using public-domain medical data, we run an
      automated causal discovery system, CaMML, which allows the incorporation of
      multiple kinds of prior expert knowledge into its search, to test and compare
      unbiased discovery with discovery biased with different kinds of expert opinion.
      We use adjacency matrices enhanced with numerical and colour labels to assist
      with the interpretation of the results. We present an algorithm for generating a
      single BN from a set of learned BNs that incorporates user preferences regarding
      complexity vs completeness. These techniques are presented as part of the first
      detailed workflow for hybrid structure learning within the broader knowledge
      engineering process. RESULTS: The detailed knowledge engineering workflow is
      shown to be useful for structuring a complex iterative BN development process.
      The adjacency matrices make it clear that for our medical case study using the
      IOWA dataset, the simplest kind of prior information (partially sorting variables
      into tiers) was more effective in aiding model discovery than either using no
      prior information or using more sophisticated and detailed expert priors. The
      method for generating a single BN captures relationships that would be overlooked
      by other approaches in the literature. CONCLUSION: Hybrid causal learning of BNs
      is an important emerging technology. We present methods for incorporating it into
      the knowledge engineering process, including visualisation and analysis of the
      learned networks.

PMID- 21958684
TI  - Infection rates associated with total parenteral nutrition.
AB  - The use of central venous access devices is increasingly common within
      healthcare, and such devices carry an associated risk of infection. Additional
      risk reduction strategies need exploring to reduce avoidable infections. A
      prospective 12-month audit was performed on the use of 2% chlorhexidine gluconate
      transparent, antimicrobial dressing to cover the catheter exit site in patients
      receiving total parenteral nutrition. The results showed a decrease in catheter
      related bloodstream infection (CRBSI) from eight cases to zero (P=0.057), making
      this film dressing a possible useful addition in the goal of zero avoidable
      CRBSIs within this high risk group of patients.

PMID- 21958685
TI  - Nosocomial acute-onset postoperative endophthalmitis at a university teaching
      hospital in China.
AB  - A retrospective study of all intra-ocular operations performed at Zhongshan
      Ophthalmic Centre, China between 1 January 2000 and 30 December 2009 was
      conducted to gain further knowledge about nosocomial acute-onset postoperative
      endophthalmitis. In total, 147,244 intra-ocular operations were performed during
      this period. Acute-onset postoperative endophthalmitis was diagnosed in 29 cases,
      giving a frequency of 0.020%. The frequency remained low and did not increase
      over the 10-year period. The highest rate of endophthalmitis was found following
      secondary intra-ocular lens implantation (0.129%). Cataract surgery had a rate of
      0.01%, which is on the lower end of estimates from other large-scale studies.
      Gram-positive bacteria were the most commonly isolated organisms (71%), with the
      majority being Staphylococcus epidermidis (64%). However, no S. epidermidis was
      identified in the cases following cataract extraction; these patients received
      intracameral vancomycin at the end of the procedure. Visual outcomes of patients
      with postoperative endophthalmitis were generally poor. Three (10%) patients had
      visual acuity (VA) >=20/40 at the final follow-up visit (all had undergone
      cataract surgery) and 15 (52%) patients had VA <=20/400 at the final follow-up
      visit (10 had undergone pars plana vitrectomy). Factors associated with poor
      visual outcomes included initial VA of hand motions or worse, and positive
      culture results. The results of this 10-year study may serve as a source of
      comparison for other centres and future studies.

PMID- 21958687
TI  - Boosting and suppressing mitotic phosphorylation.
AB  - Reversible protein phosphorylation is an essential aspect of mitosis and forms
      the basis of nuclear envelope breakdown, chromosome condensation and spindle
      assembly. Through global phosphoproteomic analysis, it has become clear that
      overall protein phosphorylation and phosphosite occupancy is most abundant during
      mitosis. At mitotic exit, this abundant phosphorylation must be reversed, and
      this process requires massive and rapid protein dephosphorylation. In addition to
      this global shift in protein phosphorylation, careful spatial control of protein
      (de)phosphorylation is equally important for spindle assembly, chromosome
      disjunction and chromosome alignment. In this review, we discuss the underlying
      mechanisms that enforce the dramatic global shift in protein phosphorylation as
      well as the mechanisms that allow for highly localized substrate phosphorylation
      in mitosis.

PMID- 21958686
TI  - Changes in the expression and subcellular distribution of galectin-3 in clear
      cell renal cell carcinoma.
AB  - BACKGROUND: Clear cell renal cell carcinoma, a solid growing tumor, is the most
      common tumor in human kidney. Evaluating the usefulness of beta-galactoside
      binding galectin-3 as a diagnostic marker for this type of cancer could open
      avenues for preventive and therapeutic strategies by employing specific
      inhibitors of the lectin. To study a putative correlation between the extent of
      galectin-3 and the development of clear cell renal cell carcinoma, we monitored
      the quantity and distribution of this lectin in tissue samples from 39 patients.
      METHODS: Galectin-3 concentrations in normal, intermediate and tumor tissues were
      examined by immunofluorescence microscopy and on immunoblots with antibodies
      directed against galectin-3 and renal control proteins. The cell nuclei were
      isolated to determine quantities of galectin-3 that were transferred into this
      compartment in normal or tumor samples. RESULTS: Immunofluorescence data revealed
      a mosaic pattern of galectin-3 expression in collecting ducts and distal tubules
      of normal kidney. Galectin-3 expression was significantly increased in 79% of
      tumor samples as compared to normal tissues. Furthermore, we observed an increase
      in nuclear translocation of the lectin in tumor tissues. CONCLUSIONS: Our data
      indicate that changes in the cellular level of galectin-3 correlate with the
      development of clear cell renal cell carcinoma, which is in line with previously
      published data on this specific type of tumor. In most of these studies the
      lectin tends to be highly expressed in tumor tissues. Furthermore, this study
      suggests that the increase in the proportion of galectin-3 affects the balance
      from a cytosolic distribution towards translocation into the nucleus.

PMID- 21958688
TI  - Staying in touch: the molecular era of organelle contact sites.
AB  - Membrane contact sites (MCS) are close appositions between two organelles that
      facilitate both signaling and the passage of ions and lipids from one cellular
      compartment to another. Despite the fact that MCS have been observed for over 50
      years now, we still know very little about the molecular machinery required to
      create them or their structure, function and regulation. In this review, we focus
      on the three best-characterized contact sites to date: the nucleus-vacuole
      junction and mitochondria-ER and plasma membrane-ER contact sites. In addition,
      we discuss principles arising from recent research and highlight several
      unanswered questions in the field.

PMID- 21958690
TI  - Association of ethnicity with involuntary childlessness and perceived reasons for
      infertility: baseline data from the Study of Women's Health Across the Nation
      (SWAN).
AB  - OBJECTIVE: To evaluate whether ethnicity is associated with involuntary
      childlessness and perceived reasons for difficulties in becoming pregnant.
      DESIGN: Cross-sectional analysis of baseline data from a longitudinal cohort.
      SETTING: Multiethnic, community-based observational study of US women.
      PATIENT(S): Women in midlife (3,149), aged 42-52 years. INTERVENTION(S): None.
      MAIN OUTCOME MEASURE(S): Involuntary childlessness and perceived etiology of
      infertility. RESULT(S): One hundred thirty-three subjects (4.2%) were
      involuntarily childless, defined by a reported history of infertility and
      nulliparity. Ethnicity was significantly associated with self-reported
      involuntary childlessness. After controlling for economic and other risk factors,
      African American (odds ratio [OR] 0.30; 95% confidence interval [CI] 0.15-0.59)
      and Chinese women (OR 0.36; 95% CI 0.14-0.90) were less likely to suffer from
      involuntary childlessness compared with non-Hispanic white women. In addition,
      302 subjects reported a perceived etiology of infertility. An unexpectedly large
      proportion of these women (24.5%, 74 of 302) reported etiologies not known to
      cause infertility (i.e., tipped uterus, ligaments for tubes were stretched), with
      African American women having been most likely to report these etiologies (OR
      2.81; 95% CI 1.26-6.28) as the reason for not becoming pregnant. CONCLUSION(S):
      Ethnicity is significantly associated with involuntary childlessness and
      perceived etiology of infertility. Misattribution of causes of infertility is
      common and merits further consideration with respect to language or cultural
      barriers, as well as possible physician misattribution.

PMID- 21958689
TI  - Genetic variation in the sex hormone metabolic pathway and endometriosis risk: an
      evaluation of candidate genes.
AB  - OBJECTIVE: To evaluate the relationship between common genetic variation in genes
      involved in the biosynthesis and signaling of estrogen and progesterone and
      endometriosis risk. DESIGN: Genetic polymorphism analysis. SETTING: Population
      based case-control study conducted in Group Health Cooperative enrollees in
      western Washington. PATIENT(S): Women with newly diagnosed, surgically confirmed
      endometriosis between 1996 and 2001 (n = 256) and age- and reference year-matched
      female control subjects without a history of endometriosis (n = 567).
      INTERVENTIONS(S): None. MAIN OUTCOME MEASURE(S): We evaluated the relationship
      between common genetic variation and endometriosis risk, using gene-based tests
      and single-variant analysis of genetic polymorphisms in ESR1, ESR2, PGR, CYP17A1,
      CYP19A1, HSD17B1, HSD17B2, CYP1A1, CYP1A2, COMT, and GSTM1. RESULT(S): The most
      consistent gene-based association with endometriosis risk was for CYP19A1. We did
      not find evidence for consistent significant associations between previously
      reported candidate SNPs in sex hormone-related genes and endometriosis risk.
      CONCLUSION(S): In summary, we report increased endometriosis risk with CYP19A1
      gene-based tests; replication of the association between endometriosis and this
      gene or gene region is necessary in a larger study population.

PMID- 21958691
TI  - Sperm morphology: classification drift over time and clinical implications.
AB  - OBJECTIVE: To assess sperm morphology with Tygerberg (strict) and World Health
      Organization (WHO) 3rd criteria for intrauterine inseminations (IUI) between two
      eras to determine if there was a difference in pregnancy rates. DESIGN:
      Retrospective study. SETTING: Academic institution. PATIENT(S): 127 couples with
      290 IUI treatments during 1996-97 (era 1) and 133 couples with 317 IUI treatments
      during 2005-06 (era 2). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Pregnancy
      rates per cycle and couple. RESULT(S): Average sperm morphology was higher in era
      1 than era 2 for both WHO 3rd (37 +/- 13% vs. 23 +/- 10%) and strict criteria
      (8.0 +/- 5.0% vs. 4.0 +/- 3.0%). Pregnancy rates per cycle were 5.9% versus 19.8%
      in era 1 and 16.7% versus 19.3% in era 2 for couples with WHO 3rd morphology <30%
      or >=30%, respectively. Pregnancy rates per cycle were 2.7% versus 15.0% in era 1
      and 13.3% versus 14.7% in era 2 for couples with strict morphology <=4% or >4%,
      respectively. CONCLUSION(S): There was a strong relationship between morphology
      and IUI outcome in era 1 that was not present in era 2. These results suggest
      that classification drift increased the percentage of men diagnosed with
      teratozoospermia and resulted in a loss of predictive value.

PMID- 21958692
TI  - Postoperative chemoradiation for resected gastric cancer--is the Macdonald
      Regimen Tolerable? a retrospective multi-institutional study.
AB  - BACKGROUND: Postoperative chemoradiation as per Intergroup-0116 trial ("Macdonald
      regimen") is considered standard for completely resected high risk gastric
      cancer. However, many concerns remain with regards to the toxicity of this
      regimen. To evaluate the safety and tolerability of this regimen in a routine
      clinical practice setting, we analyzed our experience with its use. As we did not
      expect a different toxic profile in patients (pts) with positive margins (R1
      resection), these were studied together with pts after complete resection (R0).
      PATIENTS AND METHODS: Postoperative chemoradiation therapy was given according to
      the original Intergroup-0116 regimen. Overall survival (OS) and disease free
      survival (DFS) rates were calculated using the Kaplan-Meier method. Comparison of
      OS and DFS between R0 and R1 pts was done using the log-rank test. RESULTS:
      Between 6/2000 and 12/2007, 166 pts after R0 (129 pts) or R1 (37 pts) resection
      of locally advanced gastric adenocarcinoma received postoperative chemoradiation;
      61% were male and the median age was 63 years (range, 23-86); 78% had T >= 3
      tumors and 81% had N+ disease; 87% of the pts completed radiotherapy and 54%
      completed the entire chemoradiation plan; 46.4% had grade >= 3 toxicity and 32%
      were hospitalized at least once for toxicity. Three pts (1.8%) died of toxicity:
      diarrhea (1), neutropenic sepsis (1) and neutropenic sepsis complicated by small
      bowel gangrene (1). The most common hematological toxicity was neutropenia, grade
      >= 3 in 30% of pts and complicated by fever in 15%. The most common non
      hematological toxicities were nausea, vomiting and diarrhea. With a median follow
      up of 51 months (range, 2-100), 62% of the R0 patients remain alive and 61% are
      free of disease. Median DFS and OS for R0 were not reached. R0 pts had a
      significantly higher 3-year DFS (60% vs. 29%, p = 0.001) and OS (61% vs. 33%, p =
      0.01) compared with R1 pts. CONCLUSIONS: In our experience, postoperative
      chemoradiation as per Intergroup-0116 seems to be substantially toxic, with a
      mortality rate which seems higher than reported in that trial. Efficacy data
      appears comparable to the original report. Following postoperative
      chemoradiation, involvement of surgical margins still has a detrimental impact on
      patient outcome.

PMID- 21958693
TI  - Three siblings with Cerebrotendinous Xanthomatosis: a novel mutation in the
      CYP27A1 gene.
AB  - Cerebrotendinous Xanthomatosis (CTX) is a rare autosomal recessive lipid storage
      disease caused by sterol 27-hydroxylase (CYP27) deficiency. We report three CTX
      siblings that shared a novel mutation of the CYP27A1 gene. These siblings
      presented with elevated cholestanol levels and typical manifestations such as
      tendon xanthomas, cataracts, osteopenia, mental retardation, cerebellar ataxia
      and peripheral neuropathy. All shared the same genetic mutation,
      c.1146_1151delins and c.1214G>A of CYP27A1. All were treated with 750 mg/day
      chenodeoxycholic acid (CDCA). In conclusion, one should consider the possibility
      of CTX in any individual with normocholesterolemic xanthomatosis, early-onset
      cataracts, mental retardation, cerebellar ataxia and peripheral neuropathy.

PMID- 21958694
TI  - Histone demethylation and steroid receptor function in cancer.
AB  - Steroid receptors recruit various cofactors to form multi-protein complexes which
      locally alter chromatin structure and control DNA accessibility in order to
      regulate gene transcription. Some of these factors are enzymes that add or remove
      histone marks in the vicinity of regulatory regions of target genes. Numerous
      histone modifications added by specific writer enzymes and removed by eraser
      enzymes have been identified. Histone methylation is a modification with a
      complex outcome, as it can lead to gene activation or repression, depending on
      the modified residue and the context. Methylation marks are added by different
      enzyme families displaying exquisite substrate specificity. Lysine methylation is
      reversible and two different demethylase families have been identified in humans,
      the Jumonji C and the lysine-specific demethylase families. A regulatory role of
      histone demethylases in fine-tuning the function of steroid receptors, especially
      the androgen receptor and estrogen receptor, has emerged in recent years. This is
      mostly inferred from in vitro studies, but more recently first in vivo data have
      further supported this concept. This and the deregulated expression observed for
      several histone demethylases suggest a role in tumours such as prostate and
      breast cancer.

PMID- 21958695
TI  - Impact of chromatin structure on PR signaling: transition from local to global
      analysis.
AB  - The progesterone receptor (PR) interacts with chromatin in a highly dynamic
      manner that requires ongoing chromatin remodeling, interaction with chaparones
      and activity of the proteasome. Here we discuss dynamic interaction of steroid
      receptor with chromatin, with special attention not only to PR but also to the
      glucocorticoid receptor (GR), as these receptors share many similarities
      regarding interaction with, and remodeling of, chromatin. Both receptors can bind
      nucleosomal DNA and have accordingly been described as pioneering factors.
      However recent genomic approaches (ChIP-seq and DHS-seq) show that a large
      fraction of receptor binding events occur at pre-accessible chromatin. Thus
      factors which generate and maintain accessible chromatin during development, and
      in fully differentiated tissue, contribute a major fraction of receptor tissue
      specificity. In addition, chromosome conformation capture techniques suggest that
      steroid receptors preferentially sequester within distinct nuclear hubs. We will
      integrate dynamic studies from single cells and genomic studies from cell
      populations, and discuss how genomic approaches have reshaped our current
      understanding of mechanisms that control steroid receptor interaction with
      chromatin.

PMID- 21958696
TI  - Two novel mutations in the thyroglobulin gene as cause of congenital
      hypothyroidism: identification a cryptic donor splice site in the exon 19.
AB  - Thyroglobulin (TG) is a homodimeric glycoprotein synthesized by the thyroid
      gland. To date, 52 mutations of the TG gene have been identified in humans. The
      purpose of the present study was to identify and characterize new mutations in
      the TG gene. We report a French patient with congenital hypothyroidism, mild
      enlarged thyroid gland and low levels of serum TG. Sequencing of DNA, genotyping,
      expression of chimeric minigenes as well as bioinformatics analysis were
      performed. DNA sequencing identified the presence of compound heterozygous
      mutations in the TG gene: the paternal mutation consists of a c.3788-3789insT or
      c.3788dupT, whereas the maternal mutation consists of g.IVS19+3_+4delAT. Minigene
      analysis of the g.IVS19+3_+4delAT mutant showed that the exon 19 is skipped
      during pre-mRNA splicing or partially included by use of cryptic 5' splice site
      located to 100 nucleotides downstream of the wild type exon-intron junction. The
      c.3788-3789insT mutation results in a putative truncated protein of 1245 amino
      acids, whereas g.IVS19+3_4delAT mutation originates two putative truncated
      proteins of 1330 and 1349 amino acids. In conclusion, we show that the
      g.IVS19+3_+4delAT mutation promotes the activation of a cryptic donor splice site
      in the exon 19 of the TG gene. These results open up new perspectives in the
      knowledge of the mechanism of splicing for the TG pre-mRNA.

PMID- 21958698
TI  - [Hip fracture surgery in the elderly patient: epidemiological data and risk
      factors].
AB  - Health care administration is concerned about the escalating cost of geriatric
      trauma care and more specifically hip fracture (HF). By 2050, the wordwide annual
      incidence of HF among elderly people will be 4.5 million (predictible incidence
      in France: 150,000) and prevention will be more important than ever. The risk of
      hip fracture in older people increases exponentially with age. The main other
      risk factors are osteoporosis and osteopenia, gender, weight, physical activity.
      The most important cause of osteoporosis is the gradual bone loss that occurs
      after the menopause. Similarly, there is a strong association with gender: the
      female-to-male ratio of HF is greater than 2/1 in people over 50 years of age
      (mean age: 83.2 yrs in female and 79.6 yrs in male in France). One year mortality
      after hip fracture is remarkably high, around 20 to 30%.

PMID- 21958699
TI  - Urinary excretion of liver-type fatty acid-binding protein as a marker of
      progressive kidney function deterioration in patients with chronic
      glomerulonephritis.
AB  - BACKGROUND: To evaluate the value of basal urinary L-FABP (uL-FABP) excretion as
      a prognostic indicator of the progression of kidney function impairment in
      patients with chronic glomerulonephritis (CGN). METHODS: One hundred twenty-three
      patients with newly diagnosed, biopsy-proven primary CGN were included. In all
      patients, and in 28 healthy subjects, uL-FABP was measured using an ELISA. Risk
      factors of the progression of kidney function were evaluated. The patients were
      in follow-up for at least 5 years. RESULTS: uL-FABP in the patients with CGN
      (76.58+/-17.3 MUg/g.cr) was greater than in the healthy subjects. A significant
      positive correlation between uL-FABP and proteinuria (R=0.501, P<0.01), serum
      creatinine (R=0.601, P<0.01) were found. Kaplan-Meier analysis revealed that uL
      FABP >76.58 MUg/g.cr predicts progression of renal function. The cut off values
      for L-FABP at 119.8 MUg/g.cr was found to be more sensitive, area under the curve
      (AUC) was 0.95. CONCLUSION: Urinary L-FABP may be a useful clinical biomarker for
      monitoring chronic glomerular disease. Urinary L-FABP can help predict the
      progression of chronic glomerular disease.

PMID- 21958701
TI  - The relation between body semantics and spatial body representations.
AB  - The present study addressed the relation between body semantics (i.e. semantic
      knowledge about the human body) and spatial body representations, by presenting
      participants with word pairs, one below the other, referring to body parts. The
      spatial position of the word pairs could be congruent (e.g. EYE / MOUTH) or
      incongruent (MOUTH / EYE) with respect to the spatial position of the words'
      referents. In addition, the spatial distance between the words' referents was
      varied, resulting in word pairs referring to body parts that are close (e.g. EYE
      / MOUTH) or far in space (e.g. EYE / FOOT). A spatial congruency effect was
      observed when subjects made an iconicity judgment (Experiments 2 and 3) but not
      when making a semantic relatedness judgment (Experiment 1). In addition, when
      making a semantic relatedness judgment (Experiment 1) reaction times increased
      with increased distance between the body parts but when making an iconicity
      judgment (Experiments 2 and 3) reaction times decreased with increased distance.
      These findings suggest that the processing of body-semantics results in the
      activation of a detailed visuo-spatial body representation that is modulated by
      the specific task requirements. We discuss these new data with respect to
      theories of embodied cognition and body semantics.

PMID- 21958700
TI  - Establishment of chemiluminescence enzyme immunoassay for apolipoprotein B-48 and
      its clinical applications for evaluation of impaired chylomicron remnant
      metabolism.
AB  - BACKGROUND: Apolipoprotein B-48 (apoB-48) is a constituent of chylomicron
      remnants synthesized in the small intestines. The serum concentration of apoB-48
      at fasting has been reported to be a marker of postprandial hyperlipidemia, a
      presumed risk factor for atherosclerosis. METHODS: We evaluated the basal
      performance of a recently developed chemiluminescent enzyme immunoassay (CLEIA).
      We also examined the correlations between serum apoB-48 concentrations and other
      lipid concentrations or life style patterns, including smoking and drinking. We
      analyzed the data of 273 clinical samples by multiple regression analysis to
      examine the influence of other serum lipid values, age, sex, smoking, drinking
      status and BMI on serum apoB-48 values. RESULTS: Within-run and between-run
      precision was obtained with 1.7-2.7% and 1.2-7.3%, respectively. The
      correlativity of enzyme-linked immunosorbent assay was correlation coefficient
      r=0.953, and regression y=1.02*-1.59. Serum apoB-48 concentrations were higher in
      males than in females, and were correlated with the status of smoking as well as
      with remnant-like particle-cholesterol (RLP-C) concentrations. Patients with the
      metabolic syndrome showed higher values of serum apoB-48 compared with control
      subjects. CONCLUSION: Serum apoB-48 measurement by CLEIA was satisfactory for
      clinical use to assess abnormalities in the chylomicron remnant metabolism.

PMID- 21958702
TI  - Bioenergy plants in the United States and China.

PMID- 21958697
TI  - Reproductive and developmental toxicity of dioxin in fish.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD or dioxin) is a global environmental
      contaminant and the prototypical ligand for investigating aryl hydrocarbon
      receptor (AHR)-mediated toxicity. Environmental exposure to TCDD results in
      developmental and reproductive toxicity in fish, birds and mammals. To resolve
      the ecotoxicological relevance and human health risks posed by exposure to dioxin
      like AHR agonists, a vertebrate model is needed that allows for toxicity studies
      at various levels of biological organization, assesses adverse reproductive and
      developmental effects and establishes appropriate integrative correlations
      between different levels of effects. Here we describe the reproductive and
      developmental toxicity of TCDD in feral fish species and summarize how using the
      zebrafish model to investigate TCDD toxicity has enabled us to characterize the
      AHR signaling in fish and to better understand how dioxin-like chemicals induce
      toxicity. We propose that such studies can be used to predict the risks that AHR
      ligands pose to feral fish populations and provide a platform for integrating
      risk assessments for both ecologically relevant organisms and humans.

PMID- 21958703
TI  - Over-expression of JcDREB, a putative AP2/EREBP domain-containing transcription
      factor gene in woody biodiesel plant Jatropha curcas, enhances salt and freezing
      tolerance in transgenic Arabidopsis thaliana.
AB  - Jatropha curcas L. is an all-purpose biodiesel plant and is widely distributed in
      tropical and subtropical climates. It can grow well on poor quality soil which is
      not qualified for crop cultivation. This is very important for relieving land,
      food and energy crises. However, tropical and subtropical distribution limits the
      production of J. curcas seed. So it is valuable to know the molecular mechanism
      of J. curcas response to adverse abiotic environmental factors, especially
      freezing stress, in order to change the plant's characteristics. Until now there
      are just a few reports about J. curcas molecular biology. In this paper, we
      cloned and characterized a DNA binding protein from this plant, designated as
      JcDREB. Sequence analysis and yeast one-hybrid assays show that JcDREB can
      effectively function as a transcription factor of DREB protein family belonging
      to A-6 subgroup member. Expression patterns of JcDREB showed that it was induced
      by cold, salt and drought stresses, not by ABA. Over-expression of JcDREB in
      transgenic Arabidopsis exhibited enhanced salt and freezing stresses.
      Understanding the molecular mechanisms of J. curcas responses to environmental
      stresses, for example, high salinity, drought and low temperature, is crucial for
      improving their stress tolerance and productivity. This work provides more
      information about A-6 subgroup members of DREB subfamily.

PMID- 21958704
TI  - Identification and expression analysis of two small heat shock protein cDNAs from
      developing seeds of biodiesel feedstock plant Jatropha curcas.
AB  - Plant small heat shock proteins (sHSPs) are known to be important for
      environmental stress tolerance and involved in various developmental processes.
      In this study, two full-length cDNAs encoding sHSPs, designated JcHSP-1 and JcHSP
      2, were identified and characterized from developing seeds of a promising
      biodiesel feedstock plant Jatropha curcas by expressed sequence tag (EST)
      sequencing of embryo cDNA libraries and rapid amplification of cDNA ends (RACE).
      JcHSP-1 and JcHSP-2 contained open-reading frames encoding sHSPs of 219 and 157
      amino acids, with predicted molecular weights of 24.42kDa and 18.02kDa,
      respectively. Sequence alignment indicated that both JcHSP-1 and JcHSP-2 shared
      high similarity with other plant sHSPs. Real-time quantitative RT-PCR analysis
      showed that the transcriptional level of both JcHSP-1 and JcHSP-2 increased along
      with natural dehydration process during seed development. A sharp increase of
      JcHSP-2 transcripts occurred in response to water content dropping from 42% in
      mature seeds to 12% in dry seeds. Western blot analysis revealed that the
      accumulation profile of two cross-reacting proteins, whose molecular weight
      corresponding to the calculated size of JcHSP-1 and JcHSP-2, respectively, was
      well consistent with the mRNA expression pattern of JcHSP-1 and JcHSP-2 in
      jatropha seeds during maturation and natural dehydration. These results indicated
      that both JcHSPs might play an important role in cell protection and seed
      development during maturation of J. curcas seeds.

PMID- 21958705
TI  - Adaptability evaluation of switchgrass (Panicum virgatum L.) cultivars on the
      Loess Plateau of China.
AB  - In the study, the growth traits, photosynthesis and morphology characteristics of
      several cultivars of switchgrass (Panicum virgatum L.) have been assessed the
      yield potential and adaptability in diverse environments (Yangling, Dingbian of
      Shaanxi province, Guyuan of Ningxia) on the Loess Plateau of China. Alamo was the
      best adapted switchgrass cultivar for biomass production in Yangling with dry
      matter (DM) yields of 44.22t/ha; Illinois USA and Cave-in-Rock grown at Guyuan
      had DM yield of 10.59t/ha and 9.36t/ha, respectively. Similarly, Cave-in-Rock in
      Dingbian performed better than others except the lowland cultivars (Alamo and
      Kanlow), which could not overcome cold stress at Guyuan and Dingbian. Moreover,
      Cave-in-Rock and Nebraska 28 has the highest photosynthesis rate which reflects
      its high productivity. Nebraska 28 and Pathfinder shown strong drought tolerance
      due to their higher WUE. It appears that the upland cultivars with high ploidy
      (e.g. 8n) would have better establishment than lowland varieties there. Optimal
      mown management seems to enhance the growth and productivity of switchgrass.
      Morphological characteristics were further studied using light-and scanning
      electron microscopy (SEM). Silica particles, vacuole size and other traits in
      switchgrass tissues (stem, leaf and root), as well as trichomes (leaf) showed
      that Cave-in-Rock and Pathfinder had larger stoma area, up to 824.4MUm(2) and
      770.1MUm(2), respectively. Silica particle length was the longest in Pathfinder
      and shortest in Cave-in-Rock. There was a highest density of silica particles in
      cv. Forestberg, and lowest in Cave-in-Rock and Pathfinder. The morphological
      characters seemed to be associated with their ploidy levels and the arid habitat
      from which they were selected. Therefore, if switchgrass is to be introduced and
      extended on the Loess Plateau of China, Cave-in-Rock and other upland cultivars
      with a high chromosome ploidy might be optimal choices for biomass plants.

PMID- 21958706
TI  - Biomass allocation, relative competitive ability and water use efficiency of two
      dominant species in semiarid Loess Plateau under water stress.
AB  - A better understanding of the growth and interspecific competition of native
      dominant species under water stress should aid in prediction of succession in
      plant communities. In addition, such research would guide the selection of
      appropriate conservation and agricultural utilization of plants in semiarid
      environments that have not been very well characterized. Biomass production and
      allocation, relative competitive ability and water use efficiency of one C(4)
      herbaceous grass (Bothriochloa ischaemum) and one C(3) leguminous subshrub
      (Lespedeza davurica), both important species from the semiarid Loess Plateau of
      China, were investigated in a pot-cultivation experiment. The experiment was
      conducted using a replacement series design in which B. ischaemum and L. davurica
      were grown with twelve plants per pot, in seven combinations of the two species
      (12:0, 10:2, 8:4, 6:6, 4:8, 2:10, and 0:12). Three levels of water treatments
      included sufficient water supply (HW), moderate water stress (MW) and severe
      water stress (LW). These treatments were applied after seedling establishment and
      remained until the end of the experiment. Biomass production and its
      partitioning, and transpiration water use efficiency (TWUE) were determined at
      the end of the experiment. Interspecific competitive indices (competitive ratio
      (CR), aggressiveness (A) and relative yield total (RYT)) were calculated from the
      dry weight for shoots, roots and total biomass. Water stress decreased biomass
      production of both species in monoculture and mixture. The growth of L. davurica
      was restrained in their mixtures for each water treatment. L. davurica had
      significantly (P<0.05) greater root:shoot allocation than B. ischaemum for each
      water treatment and proportion within the replacement series. Aggressiveness (A)
      values for B. ischaemum with respect to L. davurica were negative only at the
      proportions of B. ischaemum to L. davurica being 8:4 and 10:2 in LW treatment. B.
      ischaemum had a significantly (P<0.05) higher CR value under each water
      treatment, and water stress considerably reduced its relative CR while increased
      that of L. davurica. RYT values of the two species indicated some degree of
      resource complimentarity under both water sufficient and deficit conditions. The
      results suggest that it is advantageous for growing the two species together to
      maximize biomass production, and the suggested ratio was 10:2 of B. ischaemum to
      L. davurica because of significantly higher (P<0.05) RYT and TWUE under low water
      availability condition.

PMID- 21958707
TI  - Cloning two P5CS genes from bioenergy sorghum and their expression profiles under
      abiotic stresses and MeJA treatment.
AB  - Sweet sorghum (Sorghum bicolor (Linn.) Moench) has promise as a bioenergy
      feedstock in China and other countries for its use in the production of ethanol
      as the result of its high fermentable sugar accumulation in stems. To boost
      biofuel production and extend its range, we seek to improve its stress tolerance.
      Proline acts as an osmolyte that accumulates when plants are subjected to abiotic
      stress. P5CS (Delta1-pyrroline-5-carboxylate synthetase) is a key regulatory
      enzyme that plays a crucial role in proline biosynthesis. We isolated two closely
      related P5CS genes from sweet sorghum, designated SbP5CS1 (GenBank accession
      number: GQ377719) and SbP5CS2 (GenBank accession number: GQ377720), which are
      located on chromosome 3 and 9 and encode 729 and 716 amino acid polypeptides,
      respectively. The homology between the two sweet sorghum P5CS genes was 76%.
      Promoter analysis of the two P5CS genes revealed that both sequences not only
      contained the expected cis regulatory regions such as TATA and CAAT boxes, but
      also had many stress response elements. Expression analysis revealed that SbP5CS1
      and SbP5CS2 transcripts were up-regulated after treatment of 10-day-old seedlings
      of sweet sorghum with drought, salt (250mM NaCl) and MeJA (10MUM). The expression
      levels of the both SbP5CS genes were significantly increased after 3-day drought
      stress. Under high salt treatment, peak SbP5CS1 expression was detected at 4h and
      8h for SbP5CS2 in roots, while the trends of expression were nearly identical in
      leaves. In contrast, under drought and high salt stress, the up-regulated
      expression of SbP5CS1 was higher than that of SbP5CS2. When the seedlings were
      exposed to MeJA, rapid transcript induction of SbP5CS1 was detected at 2h in
      leaves, and the SbP5CS2 expression level increase was detected at 4h post
      treatment. SbP5CS1 and SbP5CS2 also show different temporal and spatial
      expression patterns. SbP5CS2 gene was ubiquitously expressed whereas SbP5CS1 was
      mainly expressed in mature vegetative and reproductive organs. Proline
      concentration increased after stress application and was correlated with SbP5CS
      expression. Our results suggest that the SbP5CS1 and SbP5CS2 are stress inducible
      genes but might play non-redundant roles in plant development. The two genes
      could have the potential to be used in improving stress tolerance of sweet
      sorghum and other bioenergy feedstocks.

PMID- 21958708
TI  - The differential proteome of endosperm and embryo from mature seed of Jatropha
      curcas.
AB  - Jatrpha curcas L., a non-model woody plant belonging to Euphorbiaceae family, is
      a promising economic plant due to the high oil content in seed and high tolerance
      to drought and salt stress. The embryo and endosperm of J. curcas seed differ in
      morphology, function and ploidy. To characterize the protein profiles of these
      two tissues, we have performed proteomic analysis with the dry mature J. curcas
      seeds. The data showed that the 2-DE profiles of endosperm and embryo were
      similar to each other. There are 66 differential proteins between the two seed
      tissues, in which 28 proteins distributed in 9 distinct functional classes, have
      been identified successfully in endosperm or embryo. The major groups of
      differential proteins are associated with metabolism (25%) and disease/defence
      (18%). Our results demonstrated that in the dry mature J. curcas seeds, the
      proteins involved in oil mobilization, signal transduction, transcription,
      protein synthesis, and cell cycle which are essential for the seed germination
      have occurred in endosperm and embryo, reflecting the fact that proteins required
      for germination are already present in the dry mature seed.

PMID- 21958709
TI  - A putative flowering-time-related Dof transcription factor gene, JcDof3, is
      controlled by the circadian clock in Jatropha curcas.
AB  - Plant-specific DNA-binding transcription factors with one finger (Dof) perform
      important roles in several biological processes. A yeast one-hybrid cDNA library
      of Jatropha curcas was used to identify Dof-type transcription factors. JcDof3,
      isolated from the library as a full-length cDNA, encoded a protein of 518 amino
      acids and contained a highly conserved Dof domain. Yeast one-hybrid systems and
      subcellular localization assays confirmed that JcDof3 was a typical transcription
      factor. In contrast to arrhythmic expression at basal level in etiolated
      cotyledons under continuous dark conditions, the circadian oscillations of JcDof3
      transcripts were observed under long day, short day or continuous light regimes.
      A phylogenetic analysis showed that JcDof3 was clustered into the same clade with
      CYCLING DOF FACTOR (CDF), which interacts with F-box protein to regulate
      photoperiodic flowering. Moreover, a yeast two-hybrid assay showed that JcDof3
      also interacted with F-box proteins. Our results suggest that JcDof3 is a
      circadian clock regulated gene, and might be involved in the flowering time
      regulation of J. curcas.

PMID- 21958710
TI  - Identification of candidate genes in Arabidopsis and Populus cell wall
      biosynthesis using text-mining, co-expression network analysis and comparative
      genomics.
AB  - Populus is an important bioenergy crop for bioethanol production. A greater
      understanding of cell wall biosynthesis processes is critical in reducing biomass
      recalcitrance, a major hindrance in efficient generation of biofuels from
      lignocellulosic biomass. Here, we report the identification of candidate cell
      wall biosynthesis genes through the development and application of a novel
      bioinformatics pipeline. As a first step, via text-mining of PubMed publications,
      we obtained 121 Arabidopsis genes that had the experimental evidence supporting
      their involvement in cell wall biosynthesis or remodeling. The 121 genes were
      then used as bait genes to query an Arabidopsis co-expression database, and
      additional genes were identified as neighbors of the bait genes in the network,
      increasing the number of genes to 548. The 548 Arabidopsis genes were then used
      to re-query the Arabidopsis co-expression database and re-construct a network
      that captured additional network neighbors, expanding to a total of 694 genes.
      The 694 Arabidopsis genes were computationally divided into 22 clusters. Queries
      of the Populus genome using the Arabidopsis genes revealed 817 Populus orthologs.
      Functional analysis of gene ontology and tissue-specific gene expression
      indicated that these Arabidopsis and Populus genes are high likelihood candidates
      for functional characterization in relation to cell wall biosynthesis.

PMID- 21958711
TI  - Comparative analysis of GT14/GT14-like gene family in Arabidopsis, Oryza,
      Populus, Sorghum and Vitis.
AB  - Glycosyltransferase family14 (GT14) belongs to the glycosyltransferase (GT)
      superfamily that plays important roles in the biosynthesis of cell walls, the
      most abundant source of cellulosic biomass for bioethanol production. It has been
      hypothesized that DUF266 proteins are a new class of GTs related to GT14. In this
      study, we identified 62 GT14 and 106 DUF266 genes (named GT14-like herein) in
      Arabidopsis, Oryza, Populus, Sorghum and Vitis. Our phylogenetic analysis
      separated GT14 and GT14-like genes into two distinct clades, which were further
      divided into eight and five groups, respectively. Similarities in protein domain,
      3D structure and gene expression were uncovered between the two phylogenetic
      clades, supporting the hypothesis that GT14 and GT14-like genes belong to one
      family. Therefore, we proposed a new family name, GT14/GT14-like family that
      combines both subfamilies. Variation in gene expression and protein subcellular
      localization within the GT14-like subfamily were greater than those within the
      GT14 subfamily. One-half of the Arabidopsis and Populus GT14/GT14-like genes were
      found to be preferentially expressed in stem/xylem, indicating that they are
      likely involved in cell wall biosynthesis. This study provided new insights into
      the evolution and functional diversification of the GT14/GT14-like family genes.

PMID- 21958712
TI  - Analysis of expressed sequence tags from biodiesel plant Jatropha curcas embryos
      at different developmental stages.
AB  - Jatropha curcas is considered a potential biodiesel feedstock plant whose seeds
      contain up to 40% oil. However, little is currently known about the seed biology
      of Jatropha. Therefore, it would be valuable to understand the mechanisms of
      development and lipid metabolism in Jatropha seeds. In the present study, three
      cDNA libraries were constructed with mRNA from Jatropha embryos at different
      stages of seed development. A total of 9844 expressed sequence tags (ESTs) were
      produced from these libraries, from which 1070 contigs and 3595 singletons were
      obtained. One hundred and seven unigenes were found to be differentially
      expressed in the three cDNA libraries of Jatropha embryos, indicating that these
      genes may play key roles in seed development. We have identified 59 and 61
      unigenes that might be involved in the development and lipid metabolism in
      Jatropha seeds, respectively. Some of these genes may also play important roles
      in embryogenesis, morphogenesis, defense response and adaptive mechanisms in
      plants.

PMID- 21958713
TI  - Efficient embryogenic suspension culturing and rapid transformation of a range of
      elite genotypes of sweet potato (Ipomoea batatas [L.] Lam.).
AB  - Efficient Agrobacterium tumefaciens-mediated transformation was developed using
      embryogenic suspension cell cultures of elite sweet potato (Ipomoea batatas [L.]
      Lam.) cultivars, including Ayamurasaki, Sushu2, Sushu9, Sushu11, Wanshu1, Xushu18
      and Xushu22. Embryogenic suspension cultures were established in LCP medium using
      embryogenic calli induced from apical or axillary buds on an induction medium
      containing 2 mg l(-1) 2,4-D. Suspension cultures were co-cultivated with A.
      tumefaciens strain LBA4404 harboring the binary plasmid pCAMBIA1301 with the hpt
      gene as a selectable marker and an intron-interrupted uidA gene as a visible
      marker. Several key steps of the sweet potato transformation system have been
      investigated and optimized, including the appropriate antibiotics and their
      concentrations for suppressing Agrobacterium growth and the optimal doses of
      hygromycin for transformant selection. A total of 485 putative transgenic plant
      lines were produced from the transformed calli via somatic embryogenesis and
      germination to plants under 10 mg l(-1) hygromycin and 200 mg l(-1) cefotaxime.
      PCR, GUS and Southern blot analyses of the regenerated plants showed that 92.35%
      of them were transgenic. The number of T-DNA insertions varied from one to three
      in most transgenic plant lines. Plants showed 100% survival when 308 transgenics
      were transferred to soil in the greenhouse and then to the field. Most of them
      were morphologically normal, with the production of storage roots after 3 months
      of cultivation in the greenhouse or fields. The development of such a robust
      transformation method suitable to a range of sweet potato genotypes not only
      provides a routine tool for genetic improvement via transgenesis but also allows
      us to conduct a functional verification of endogenous genes in sweet potato.

PMID- 21958714
TI  - Switchgrass (Panicum virgatum L.) cell suspension cultures: Establishment,
      characterization, and application.
AB  - Switchgrass (Panicum virgatum L.) is a warm-season perennial grass that has
      received considerable attention as a potential dedicated biofuel and bioproduct
      feedstock. Genetic improvement of switchgrass is needed for better cellulosic
      ethanol production, especially to improve cellulose-to-lignin ratios. Cell
      suspension cultures offer an in vitro system for mutant selection, mass
      propagation, gene transfer, and cell biology. Toward this end, switchgrass cell
      suspension cultures were initiated from embryogenic callus obtained from genotype
      Alamo 2. They have been established and characterized with different cell type
      morphologies: sandy, fine milky, and ultrafine cultures. Characterization
      includes histological analysis using scanning electron microscopy, and utility
      using protoplast isolation. A high protoplast isolation rate of up to 10(6)
      protoplasts/1.0g of cells was achieved for the fine milky culture, whereas only a
      few protoplasts were isolated for the sandy and ultrafine cultures. These results
      indicate that switchgrass cell suspension type sizably impacts the efficiency of
      protoplast isolation, suggesting its significance in other applications. The
      establishment of different switchgrass suspension culture cell types provides the
      opportunity to gain insights into the versatility of the system that would
      further augment switchgrass biology research.

PMID- 21958715
TI  - Age-associated reduction of stimulatory effect of ghrelin on food intake in mice.
AB  - Aging is associated with a progressive decrease in appetite and food intake. We
      focused on the age-associated changes of the stimulatory effect of the appetite
      regulating peptide, ghrelin. Food intake and the concentrations of acyl ghrelin
      and desacyl ghrelin in the plasma and in the stomach were measured with and
      without overnight fasting in young and old mice. Moreover, the food intake in
      response to the intraperitoneal administration of graded doses of acyl ghrelin
      was compared between young and old mice. Fasting drives food intake in young
      mice, but not in old mice. The concentrations of acyl ghrelin and desacyl ghrelin
      in the plasma and in the stomach were higher in the old mice than in the young
      mice. Food intake did not increase in old mice when stimulated by the
      administration of 1-3 nmol of acyl ghrelin, which could produce a significant
      increase in food intake in young mice. In conclusion, food intake did not
      increase in old mice after either overnight fasting or the administration of acyl
      ghrelin. The release and synthesis of ghrelin seem to be rather higher in old
      mice compared to young mice. These increases might be the results of compensation
      for the decline of receptor (and/or post-receptor) functions.

PMID- 21958716
TI  - LC/MS/MS identification of 20-hydroxyecdysone in a scorpion (Liocheles
      australasiae) and its binding affinity to in vitro-translated molting hormone
      receptors.
AB  - Recent advances in mass spectrometry (MS) technology have facilitated the
      detection and quantification of minor components in organisms and the
      environment. In this study, we successfully identified 20-hydroxyecdysone (20E)
      in first instar nymphs (7 days after hatching) of the scorpion Liocheles
      australasiae, using tandem mass spectrometry combined with high-performance
      liquid chromatography (LC/MS/MS). This substance was not found in adults after
      the fifth stage. Other possible molting hormone candidates such as makisterone A
      (MaA) and ponasterone A (PoA), both of which are reported to be the molting
      hormones of a few arthropod species, were not detected in this scorpion. The
      ligand-receptor binding of 20E and its analogs was quantitatively evaluated
      against the in vitro-translated molting hormone receptor, the heterodimer of
      ecdysone receptor (EcR) and the retinoid X receptor (RXR) of L. australasiae
      (LaEcR/LaRXR). The concentrations of ecdysone (E), MaA, 20E, and PoA that are
      required to inhibit 50% of [(3)H]PoA binding to the LaEcR/LaRXR complex were
      determined to be 1.9, 0.69, 0.05, and 0.017 MUM, respectively. The activity
      profiles of these 4 ecdysteroids are consistent with those obtained for the
      molting hormone receptors of several insects. The binding of a non-steroidal E
      agonist, tebufenozide, to EcR was not observed even at high concentrations,
      indicating that the structure of the ligand-binding pocket of LaEcR is not
      favorable for interaction with tebufenozide.

PMID- 21958718
TI  - Longitudinal melonychia: clinical evaluation and biopsy technique.
AB  - Longitudinal melonychia is a brown streaking of the nailbed. It is often benign
      but can be a subungual melanoma. Subungual melanoma is a rare malignancy.
      Diagnosis is often delayed, resulting in a higher staging and poorer prognosis
      than other cutaneous melanomas. We provide an update on the evaluation of
      longitudinal melonychia and biopsy technique.

PMID- 21958717
TI  - [Epidemiological study of type 1 diabetes in children under 15 years-old in
      Castilla-La Mancha (Spain)].
AB  - INTRODUCTION: We studied the incidence and prevalence of type 1 diabetes in
      children under 15 years-old in Castilla-La Mancha. PATIENTS AND METHODS:
      Incidence: All new cases in a 12 months period (2007-2008) were included. To
      calculate the completeness of ascertainment we used the capture-recapture method.
      The result is expressed in cases/100,000 inhabitants under 15 years old/year.
      Prevalence: all children under 15 years diagnosed with diabetes on 31(st) of May
      of 2008 were registered. Results are expressed as cases/1000 inhabitants under 15
      years old. RESULTS: The incidence in the Castilla-La Mancha was
      27.6/100,000/year, but there was a wide variability among the different
      provinces: Ciudad Real (34.15), Albacete (28.19), Toledo (26.57), Guadalajara
      (20.3) and Cuenca (17.6). The prevalence was 1.44/1000 children under 15 years
      old and 0.21/1000 for the whole population. By provinces: Ciudad Real (1.67),
      Albacete (1.64), Toledo (1.42), Cuenca (1.02) and Guadalajara (1.01). By sex and
      age, we found a higher incidence (13/7) and prevalence (22/7) in males under 5
      years old. The age group with highest incidence was the 4-9 year-olds, and the
      highest prevalence was in the 10-14 years group. CONCLUSIONS: Both, incidence and
      prevalence of type 1 diabetes in children under 15 years old in Castilla-La
      Mancha are high, with a wide range among the different provinces. There is a
      preponderance in males under 5 years old. The highest prevalence is that of the
      10-14 years age group. The highest incidence was in the 5-10 year age group.

PMID- 21958719
TI  - Efavirenz and 8-hydroxyefavirenz induce cell death via a JNK- and BimEL-dependent
      mechanism in primary human hepatocytes.
AB  - Chronic use of efavirenz (EFV) has been linked to incidences of hepatotoxicity in
      patients receiving EFV to treat HIV-1. While recent studies have demonstrated
      that EFV stimulates hepatic cell death a role for the metabolites of efavirenz in
      this process has yet to be examined. In the present study, incubation of primary
      human hepatocytes with synthetic 8-hydroxyEFV (8-OHEFV), which is the primary
      metabolite of EFV, resulted in cell death, caspase-3 activation and reactive
      oxygen species formation. The metabolite exerted these effects at earlier time
      points and using lower concentrations than were required for the parent compound.
      In addition, pharmacological inhibition of cytochrome P450-dependent metabolism
      of EFV using 1-aminobenzotriazole markedly decreased reactive oxygen species
      formation and cell death. Treatment of primary human hepatocytes with EFV and 8
      OHEFV also stimulated phosphorylation of c-Jun N-terminal kinase (JNK) as well as
      phosphorylation of the JNK substrate c-Jun. Further, the mRNA and protein
      expression of an isoform of Bim (Bcl-2 interacting mediator of cell death)
      denoted as BimEL, which is proapoptotic and has been shown to be modulated by
      JNK, was increased. Inhibition of JNK using SP600125 prevented the EFV- and 8
      OHEFV-mediated cell death. Silencing of Bim using siRNA transfected into
      hepatocytes also prevented cell death resulting from 8-OHEFV-treatment. These
      data suggest that the oxidative metabolite 8-OHEFV is a more potent inducer of
      hepatic cell death than the parent compound EFV. Further, activation of the JNK
      signaling pathway and BimEL mRNA expression appear to be required for EFV- and 8
      OHEFV-mediated hepatocyte death.

PMID- 21958720
TI  - 4-Chlorotetrazolo[1,5-a]quinoxaline inhibits activation of Syk kinase to suppress
      mast cells in vitro and mast cell-mediated passive cutaneous anaphylaxis in mice.
AB  - 4-Chlorotetrazolo[1,5-a]quinoxaline is a quinoxaline derivative. We aimed to
      study the effects of 4-chlorotetrazolo[1,5-a]quinoxaline on activation of mast
      cells in vitro and in mice. 4-Chlorotetrazolo[1,5-a]quinoxaline reversibly
      inhibited degranulation of mast cells in a dose-dependent manner, and also
      suppressed the expression and secretion of TNF-alpha and IL-4 in mast cells.
      Mechanistically, 4-chlorotetrazolo[1,5-a]quinoxaline inhibited activating
      phosphorylation of Syk and LAT, which are crucial for early FcepsilonRI-mediated
      signaling events, as well as Akt and MAP kinases, which play essential roles in
      the production of various pro-inflammatory cytokines in mast cells. Notably,
      although 4-chlorotetrazolo[1,5-a]quinoxaline inhibited the activation of Fyn and
      Syk, minimal inhibition was observed in mast cells in the case of Lyn.
      Furthermore, consistent with its in vitro activity, 4-chlorotetrazolo[1,5
      a]quinoxaline significantly suppressed mast cell-mediated passive cutaneous
      anaphylaxis in mice. In summary, the results from this study demonstrate that 4
      chlorotetrazolo[1,5-a]quinoxaline shows an inhibitory effect on mast cells in
      vitro and in vivo, and that this is mediated by inhibiting the activation of Syk
      in mast cells. Therefore, 4-chlorotetrazolo[1,5-a]quinoxaline could be useful in
      the treatment of mast cell-mediated allergic diseases.

PMID- 21958721
TI  - The effect of cryopreservation on the capacitation status and epithelial cell
      attachment capability of dog spermatozoa.
AB  - Freezing and cooling of spermatozoa during cryopreservation for artificial
      insemination causes ultrastructural changes in the acrosome and plasma membrane
      which reduces longevity and fertility. Cryopreservation-induced capacitation-like
      changes and reduced ability of spermatozoa to bind to the cells of the
      reproductive tract of the bitch may contribute to the reduced fertility of
      cryopreserved spermatozoa. Previous studies in the dog have investigated the
      effects of extending and cooling spermatozoa on the plasma membrane but often
      only after freeze-thawing and not in conjunction with an assessment of their
      ability to bind to uterine tube epithelial explants. This study investigated the
      effect of each stage of the cryopreservation process on capacitation and
      attachment to the reproductive tract of the bitch. The capacitation status of
      spermatozoa was studied over time after cryopreservation using a
      chlortetracycline and Hoechst 33258 stain. The ability of spermatozoa to bind to
      uterine tube epithelial explants was studied using Hoechst 33342 stain.
      Extending, cooling and freeze-thawing promoted capacitation and decreased the
      spermatozoal binding ability. The effect of each stage appeared to be cumulative
      with the freeze-thawing stage being the most dramatic. The results suggested that
      the cumulative effect of each stage of the cryopreservation process results in
      the promotion of capacitation before spermatozoa have reached the site of
      fertilisation, and therefore spermatozoa have reduced ability to attach to
      epithelial cells. These effects are contributory factors to the reduced fertility
      of cryopreserved spermatozoa.

PMID- 21958722
TI  - Stem cells and veterinary medicine: tools to understand diseases and enable
      tissue regeneration and drug discovery.
AB  - New sophisticated laboratory techniques, as well as established interactions
      between basic science, researchers and veterinarians, have led to an exponential
      increase in our understanding of the animal body in health and disease. The
      advent of animal cloning, the identification and characterization of stem cells,
      and publication of the various mammalian genomes has afforded the opportunity to
      exploit these technologies to better understand disease and develop new
      therapies. In human medicine, these medical advances are already being translated
      into clinical practice, the promise being that previously untreatable or
      incurable chronic diseases will become a thing of the past. In parallel, the
      veterinary profession is looking to these technologies to explore novel therapies
      for chronic diseases, such as osteoarthritis in companion animals, and is
      applying these technologies to enhance food animal production. This review
      focuses on the emerging area of stem cell biology and explores the potential
      applications of stem cell technologies to veterinary medicine.

PMID- 21958724
TI  - [Toward the appropriate use of teleradiology].
AB  - Teleradiology involves much more than merely transmitting images and information
      between two points: teleradiology consists of sharing knowledge and working
      together in a network. It facilitates rapid access to radiological reports and
      second opinions, remote consulting among physicians, improved patient care,
      access to complex tools for postprocessing and computer-aided diagnosis, support
      for research and training projects, ties between isolated healthcare providers
      and busier or more experienced providers, 24-hour coverage, and competition among
      radiology departments. A close relation with the radiologist leads to better
      care. However, teleradiology should not have negative effects on the efficacy of
      the clinical radiology service that is closest to the patient. This article
      focuses on the legal requirements of teleradiology services and on the clinical
      problems that can arise in teleradiology settings, with the ultimate aim of
      ensuring the appropriate use of teleradiology to improve healthcare.

PMID- 21958726
TI  - [Radiological manifestations of Baastrup's disease in children].
AB  - Baastrup's disease is not usually considered among the possible causes of low
      back pain in children. Classically, Baastrup's disease is characterized by
      degenerative phenomena secondary to friction between adjacent spinous processes,
      with sclerosis of the margins and decrease in the interspinous space. Baastrup's
      disease becomes more prevalent with age and is usually accompanied by
      degenerative changes in the vertebral column, such as lumbar facet hypertrophy or
      disc disease. Certain activities like dance or gymnastics can make Baastrup's
      disease more likely to appear at an earlier age. In children, Baastrup's disease
      can manifest in a different way, with increased interspinous spaces and bone
      remodeling. In this article, we present the cases of two patients with low back
      pain who were diagnosed with Baastrup's disease. 

PMID- 21958727
TI  - Pressed ceramics onto zirconia. Part 1: Comparison of crystalline phases present,
      adhesion to a zirconia system and flexural strength.
AB  - OBJECTIVES: To compare the crystalline phases present, quantify the adhesion to
      zirconia and measure the mechanical properties of four commercially available
      pressed ceramics suitable for zirconia substructures. MATERIALS AND METHODS: This
      study compares the X-ray diffraction response and the mechanical properties of
      four different pressed ceramics (Noritake CZR Press, Vita PM9, Wieland PressXzr
      and IPS e.max ZirPress) to Vita In-Ceram YZ zirconia substrate. The adhesion was
      determined using the interfacial strain energy release rate fracture mechanics
      approach; in addition biaxial flexural strength values of each material was
      determined. RESULTS: X-ray diffraction analysis revealed that Noritake CZR Press
      and Vita PM9 contain leucite whereas IPS e.max ZirPress and Wieland PressXzr are
      non-leucite amorphous materials. The strain energy release rate results revealed
      that the pressed ceramics with leucite have better adhesion than non-leucite
      ceramics to zirconia. Differences were observed between biaxial strength results
      for the pressed ceramics from bilayer compared with monolayer specimens.
      CONCLUSIONS: Pressed ceramics compatible with zirconia tested in this study were
      of two types; leucite containing and non-leucite containing essentially glass
      ceramics. Leucite containing pressable ceramics appears to have better adhesion
      to zirconia.

PMID- 21958728
TI  - Injury risk associated with ground hardness in junior cricket.
AB  - OBJECTIVES: To establish if there is an association between ground hardness and
      injury risk in junior cricket. DESIGN: Nested case-series of players who played
      matches on specific grounds with objective ground hardness measures, within a
      prospective cohort study of junior community club cricket players. METHODS:
      Monitoring of injuries and playing exposure occurred during 434 matches over the
      2007/2008 playing season. Objective assessment of the hardness of 38 grounds was
      undertaken using a Clegg hammer at 13 sites on 19 different junior cricket
      grounds on the match eve across the season. Hardness readings were classified
      from unacceptably low (<30 g) to unacceptably high (>120 g) and two independent
      raters assessed the likelihood of each injury being related to ground hardness.
      Injuries sustained on tested grounds were related to the ground hardness
      measures. RESULTS: Overall, 31 match injuries were reported; 6.5% were rated as
      likely to be related to ground hardness, 16.1% as possibly related and 74.2% as
      unlikely to be related and 3.2% unknown. The two injuries likely to be related to
      ground hardness were sustained whilst diving to catch a ball resulting, in a
      graze/laceration from contact with hard ground. Overall, 31/38 (82%) ground
      assessments were rated as having 'unacceptably high' hardness and all others as
      'high/normal' hardness. Only one injury occurred on an objectively tested ground.
      CONCLUSIONS: It remains unclear if ground hardness is a contributing factor to
      the most common injury mechanism of being struck by the ball, and needs to be
      confirmed in future larger-scale studies.

PMID- 21958729
TI  - Expression of HER2neu in ductal carcinoma in situ is associated with local
      recurrence.
AB  - AIMS: Determination of the risk of recurrence after local excision of ductal
      carcinoma in situ (DCIS) remains a challenge. Molecular profiling based on
      immunohistochemical staining to oestrogen receptor (ER), progesterone receptor
      (PR) and HER2neu improved risk prediction in invasive breast cancer, but few
      studies have evaluated if molecular classification of DCIS predicts local
      recurrence. We evaluated the expression of ER, PR and HER2neu in DCIS to
      determine if molecular classification predicts local recurrence after breast
      conserving therapy for DCIS. MATERIALS AND METHODS: We reviewed the records of
      patients with DCIS treated between 1987 and 2000, carried out a pathology review
      and immunohistochemical staining for ER, PR and HER2neu and categorised cases
      into four molecular phenotypes [luminal A (ER+ and/or PR+, HER2neu-), luminal B
      (ER+ and/or PR+, HER2neu+), HER2neu subtype (ER-, PR-, HER2neu+), triple negative
      (ER-, PR-, HER2neu-)]. We evaluated the association between the molecular subtype
      and the development of local recurrence. RESULTS: In total, 180 cases of DCIS
      were included in the study (luminal A, n=113; luminal B, n=25; HER2neu type,
      n=29; triple negative, n=13). The median follow-up time was 8.7 years. We
      observed higher rates of local recurrence among luminal B (40%) and HER2neu type
      (38%) DCIS compared with luminal A (21%) and triple negative (15%) DCIS. On
      multivariable analysis, HER2neu overexpression was associated with an increased
      risk of local recurrence (hazard ratio=1.98; 95% confidence interval: 1.11, 3.53,
      P=0.02). CONCLUSION: HER2neu expression in DCIS is a significant predictor of
      local recurrence, whereas luminal A and triple negative phenotypes are associated
      with relatively low risks of local recurrence.

PMID- 21958730
TI  - A role for aberrantly expressed nuclear localized decorin in migration and
      invasion of dysplastic and malignant oral epithelial cells.
AB  - BACKGROUND: Oral cancer is the sixth most common malignancy worldwide with a
      mortality rate that is higher than many other cancers. Death usually occurs as a
      result of local invasion and regional lymph node metastases. Decorin is a
      multifunctional proteoglycan of the extracellular matrix that affects the biology
      of various types of cancer. Previously; we have shown that decorin is aberrantly
      expressed in the nucleus in human dysplastic oral keratinocytes (DOK) and
      malignant squamous cells carcinoma (SCC-25) and human biopsy tissues. In this
      study, we examined the role of nuclear decorin in oral cancer progression.
      MATERIALS AND METHODS: We have used a post-transcriptional gene silencing (RNA
      interference) approach to stably knockdown nuclear decorin gene expression in DOK
      and SCC-25 cells using a specific shRNA plasmid and a combination of
      immunological and molecular techniques to study nuclear decorin function in these
      oral epithelial cell lines. RESULTS: More than 80% decorin silencing/knockdown
      was achieved as confirmed by real time PCR and western blot analysis in both DOK
      and SCC-25 cells. This RNA interference-mediated knockdown of nuclear decorin
      expression resulted in significantly reduced invasion and migration in these cell
      lines as measured by MatrigelTM coated and uncoated Trans well chamber assays
      respectively. Decorin silencing also resulted in reduced IL-8 mRNA and proteins
      levels in these cell lines. Culturing decorin silenced DOK and SCC-25 cells, with
      recombinant human IL-8 or IL-8 containing conditioned medium from respective un
      transfected cells for 24 h prior to migration and invasion experiments, resulted
      in the salvation of reduced migration and invasion phenotype. Furthermore, we
      found that nuclear localized decorin interacts with EGFR in the nuclear fractions
      of both DOK and SCC-25 cells. Interestingly, EGFR (trans) activation has
      previously been shown to be involved in IL-8 production in various epithelia.
      CONCLUSIONS: Taken together, our results indicate that nuclear localized decorin
      plays an important role in migration and invasion of oral cancer cells and thus
      may present as a novel potential target for the treatment of oral cancer.

PMID- 21958731
TI  - [Benefits of statin therapy based on plasma carbohydrate antigen 125 values
      following an admission for acute heart failure].
AB  - INTRODUCTION AND OBJECTIVES: The prognostic benefit of statins in patients with
      heart failure is a topic of controversy. Under the hypothesis that statins may
      provide greater benefit in a subgroup of patients with heightened inflammatory
      activity, we sought to explore whether statins are associated with a decreased
      risk of long-term mortality in patients with acute heart failure based on
      elevated levels of carbohydrate antigen 125, a biomarker related to systemic
      congestion and proinflammatory status. METHODS: We analysed 1222 consecutive
      patients admitted with acute heart failure in a single teaching center during a
      median follow-up of 20 months. carbohydrate antigen 125 was measured during index
      hospitalization and dichotomized according to the established reference cut-off
      (>35 U/mL). RESULTS: Increased levels of carbohydrate antigen 125 (>35 U/mL) were
      observed in 793 (64.9%) and prescription of statins registered in 455 (37.2%)
      patients. In patients with carbohydrate antigen 125 >35 U/mL, mortality was lower
      in statin-treated patients (1.89 vs 2.80 per 10 patient-years of follow-up, P
      <.001). Conversely, in those with carbohydrate antigen 125 in normal range,
      mortality did not differ (1.76 vs 1.63 per 10 patient-years of follow-up, P =
      .862). After covariate adjustment, this differential effect persisted (P for
      interaction = .024) and statin use was associated with a significant mortality
      reduction in patients with elevated values of carbohydrate antigen 125 (hazard
      ratio=0.65, 95% confidence interval: 0.51-0.82; P <.001), but not in those with
      values equal to or below 35 U/mL (hazard ratio=1.02, 95% confidence interval:
      0.74-1.41; P = .907). CONCLUSIONS: Elevation of carbohydrate antigen 125 (>35
      U/mL) identified a subset of patients with acute heart failure who could benefit
      from statin treatment in regard to total mortality.

PMID- 21958732
TI  - A silent gigantic solitary fibrous tumor of the pleura: case report.
AB  - Solitary fibrous tumor of the pleura is a rare mesenchymal tumor, representing
      less than 5% of all neoplasms associated with the pleura. A 57-year-old man had
      general malaise without chest symptoms for 1 month. A chest roentgenogram and
      computed tomography showed a giant mass in the left thorax. Although the tumor
      compressed the descending aorta and other mediastinal structures strongly,
      thereby shifting them to the right side, the patient had no symptoms except
      malaise. The tumor was successfully resected via two separate thoracotomies. The
      tumor was measured (20 cm * 19 cm * 15 cm) and weighed (2150 g). The tumor was
      histologically and immunohistochemically diagnosed as benign. Although SFT is
      benign, a long follow-up period is essential as even patients with complete
      resection are at risk of recurrence many years after surgery.

PMID- 21958733
TI  - Hyponatremia associated with levamisole-adulterated cocaine use in emergency
      department patients.
AB  - An increasing percentage of US cocaine has been adulterated with levamisole, an
      immunomodulator associated with agranulocytosis. We describe 3 emergency
      department patients with hyponatremia and cocaine use. Despite extensive
      evaluation, the cause of the hyponatremia was not elucidated but resolved during
      hospitalization. Because hyponatremia has not previously been associated with
      cocaine, we sought to uncover a plausible explanation that might be contributing
      to this new finding. Levamisole was detected in all 3 patients. Although we are
      unable to confirm causality, we propose that levamisole-adulterated cocaine may
      have contributed to the hyponatremia described in these patients.

PMID- 21958734
TI  - The RACE to where? For what?

PMID- 21958736
TI  - Identification of new antimalarial leads by use of virtual screening against
      cytochrome bc1.
AB  - Cytochrome bc(1) is a validated drug target in malaria parasites. The spread of
      Plasmodium falciparum strains resistant to multiple antimalarials emphasizes the
      urgent need for new drugs. We screened in silico the ZINC and MOE databases,
      using ligand- and structure-based approaches, to identify new leads for
      development. The most active compound presented an IC(50) value against cultured
      P. falciparum of 2 MUM and a docking pose consistent with its activity.

PMID- 21958735
TI  - Functional characterization of the human translocator protein (18kDa) gene
      promoter in human breast cancer cell lines.
AB  - The translocator protein (18kDa; TSPO) is a mitochondrial drug- and cholesterol
      binding protein that has been implicated in several processes, including
      steroidogenesis, cell proliferation, and apoptosis. Expression of the human TSPO
      gene is elevated in several cancers. To understand the molecular mechanisms that
      regulate TSPO expression in human breast cancer cells, the TSPO promoter was
      identified, cloned, and functionally characterized in poor-in-TSPO hormone
      dependent, non-aggressive MCF-7 cells and rich-in-TSPO hormone-independent,
      aggressive, and metastatic MDA-MB-231 breast cancer cells. RNA ligase-mediated 5'
      rapid amplification of cDNA ends analysis indicated transcription initiated at
      multiple sites downstream of a GC-rich promoter that lacks functional TATA and
      CCAAT boxes. Deletion analysis indicated that the region from -121 to +66, which
      contains five putative regulatory sites known as GC boxes, was sufficient to
      induce reporter activity up to 24-fold in MCF-7 and nearly 120-fold in MDA-MB-231
      cells. Electrophoretic mobility shift and chromatin immunoprecipitation assays
      indicated that Sp1, Sp3 and Sp4 bind to these GC boxes in vitro and to the
      endogenous TSPO promoter. Silencing of Sp1, Sp3 and Sp4 gene expression reduced
      TSPO levels. In addition, TSPO expression was epigenetically regulated at one or
      more of the identified GC boxes. Disruption of the sequence downstream of the
      main start site of TSPO differentially regulated TSPO promoter activity in MCF-7
      and MDA-MB-231 cells, indicating that essential elements contribute to its
      differential expression in these cells. Taken together, these experiments
      constitute the first in-depth functional analysis of the human TSPO gene promoter
      and its transcriptional regulation.

PMID- 21958737
TI  - Design, synthesis and biological evaluation of benzo[1.3.2]dithiazolium ylide 1,1
      dioxide derivatives as potential dual cyclooxygenase-2/5-lipoxygenase inhibitors.
AB  - 3-(4-Bromophenyl)-6-nitrobenzo[1.3.2]dithiazolium ylide 1,1-dioxide (5) was
      discovered as a new prototype for dual inhibitors of cyclooxygenase-2 (COX-2) and
      5-lipoxygenase (5-LOX). Thus, the structure-activity relationships of
      benzo[1.3.2]dithiazolium ylide 1,1-dioxide skeleton were carried out. The 6-NO(2)
      group played an essential role in the inhibitory activity. In addition, moderate
      sized lipophilic substituents at the para-position of the 3-aryl moiety were
      required for dual COX-2/5-LOX inhibitory activity. Among the identified potent
      dual inhibitors, 3-(4-tbutylphenyl) derivative 30c (IC(50) values of 0.27 MUM and
      0.30 MUM against COX-2 and 5-LOX, respectively) and 3-(4-biphenyl) derivative 30f
      (IC(50) values of 0.50 MUM and 0.15MUM against COX-2 and 5-LOX, respectively)
      were the most potent dual COX-2/5-LOX inhibitors. Intraperitoneal administration
      of 30c at 100mg/kg demonstrated potent acute anti-inflammatory activity. As a
      result, benzo[1.3.2]dithiazolium ylide 1,1-dioxide represented a novel scaffold
      for the exploitation in developing dual COX-2/5-LOX inhibitors.

PMID- 21958738
TI  - Bioassay-guided identification of an anti-inflammatory prenylated
      acylphloroglucinol from Melicope ptelefolia and molecular insights into its
      interaction with 5-lipoxygenase.
AB  - A bioassay-guided investigation of Melicope ptelefolia Champ ex Benth (Rutaceae)
      resulted in the identification of an acyphloroglucinol, 2,4,6-trihydroxy-3
      geranylacetophenone or tHGA, as the active principle inhibiting soybean 15-LOX.
      The anti-inflammatory action was also demonstrated on human leukocytes, where the
      compound showed prominent inhibitory activity against human PBML 5-LOX, with an
      IC(50) value of 0.42 MUM, very close to the effect produced by the commonly used
      standard, NDGA. The compound concentration-dependently inhibited 5-LOX product
      synthesis, specifically inhibiting cysteinyl leukotriene LTC(4) with an IC(50)
      value of 1.80 MUM, and showed no cell toxicity effects. The anti-inflammatory
      action does not seem to proceed via redox or metal chelating mechanism since the
      compound tested negative for these bioactivities. Further tests on
      cyclooxygenases indicated that the compound acts via a dual LOX/COX inhibitory
      mechanism, with greater selectivity for 5-LOX and COX-2 (IC(50) value of 0.40
      MUM). The molecular features that govern the 5-LOX inhibitory activity was thus
      explored using in silico docking experiments. The residues Ile 553 and Hie 252
      were the most important residues in the interaction, each contributing
      significant energy values of -13.45 (electrostatic) and -5.40 kcal/mol
      (electrostatic and Van der Waals), respectively. The hydroxyl group of the
      phloroglucinol core of the compound forms a 2.56A hydrogen bond with the side
      chain of the carboxylate group of Ile 553. Both Ile 553 and Hie 252 are crucial
      amino acid residues which chelate with the metal ion in the active site.
      Distorting the geometry of these ligands could be the reason for the inhibition
      activity shown by tHGA. The molecular simulation studies supported the bioassay
      results and served as a good model for understanding the way tHGA binds in the
      active site of human 5-LOX enzyme.

PMID- 21958739
TI  - MicroRNAs: potential diagnostic markers and therapeutic targets for EBV
      associated nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) is a highly malignant cancer with local invasion
      and early distant metastasis. NPC is highly prevalent in the Southern China and
      South-eastern Asia. The genetic susceptibility, endemic environment factors, and
      Epstein-Barr virus (EBV) infection are believed to be the major etiologic factors
      of NPC. Once metastasis occurs, the prognosis is very poor. It is urgently needed
      to develop biomarkers for early clinical diagnosis/prognosis, and novel effective
      therapies for nasopharyngeal carcinoma. In this paper, we systematically reviewed
      the current progress of miRNA studies in NPC. It has been shown that both host
      encoded miRNAs and EBV encoded miRNAs play key roles in almost all the steps of
      epithelia cell carcinogenesis, including epithelial-mesenchymal to stem-like
      transition, cell growth, migration, invasion, and tumorigenesis. More
      importantly, some miRNAs could be secreted out and play a role in the
      microenvironments. The level of sera miRNAs is correlated with the copy numbers
      of host miRNAs in tumor biopsies. Promising results of gene therapy have been
      also achieved by lentiviral delivered miRNAs. Taken together, cell free miRNAs
      would be potential biomarkers of early clinical diagnosis/prognosis; while some
      miRNAs could be further developed into therapeutic agents in the future.

PMID- 21958740
TI  - Onset of apical hypertrophic cardiomyopathy in adulthood.
AB  - The development of the hypertrophic cardiomyopathy (HC) phenotype with left
      ventricular (LV) hypertrophy usually occurs in adolescence, and documentation of
      patients with later onset of wall thickening during adulthood is rare. We report
      4 patients with asymptomatic, nonobstructive HC (3 women and 1 man) who were
      studied with serial cardiovascular magnetic resonance imaging or
      echocardiography. In these patients, LV wall thickening, confined to the apex and
      the contiguous distal portions of the ventricular septum and free wall, appeared
      in midlife and beyond. These patients were >40, >50, or >70 years old when the
      hypertrophy became evident. The maximum LV wall thickness was 14 to 25 mm (mean
      18), with a "spade" deformity of the distal chamber, associated with a nondilated
      cavity and normal ejection fraction (65% to 80%), in the absence of mitral valve
      systolic anterior motion. In each patient, similar electrocardiographic patterns
      with similar diffuse and marked T-wave inversion (with or without increased
      precordial voltages) preceded the appearance of the HC phenotype on the imaging
      studies. In conclusion, the recognition that the onset of LV hypertrophy in HC
      can be delayed well into adulthood (and even to advanced age) has important
      implications regarding the clinical screening practices for families, and
      suggests the potential value of extending prospective serial imaging beyond
      adolescence in some relatives. Electrocardiographic repolarization abnormalities
      can predict the future development of apical LV hypertrophy in adults with HC.

PMID- 21958741
TI  - Usefulness of admission red cell distribution width as a predictor of early
      mortality in patients with acute pulmonary embolism.
AB  - Red cell distribution width (RDW) is strongly associated with prognosis in
      cardiopulmonary disorders such as coronary artery disease, acute myocardial
      infarction, acute and chronic heart failure, and pulmonary hypertension. However,
      its prognostic significance in acute pulmonary embolism (PE) is unknown. The aim
      of this study was to investigate the relation between admission RDW and early
      mortality in patients with acute PE. One hundred sixty-five patients with
      confirmed acute PE were included. Patients with previous treatment for anemia,
      malignancy, or chronic liver disease, those with dialysis treatment for chronic
      renal failure, and those who received erythrocyte suspension for any reason were
      excluded. A total of 136 consecutive patients with acute PE were evaluated
      prospectively. According to receiver-operating characteristic curve analysis, the
      optimal cut-off value of RDW to predict early mortality was >14.6%, with 95.2%
      sensitivity and 53% specificity. Patients were categorized prospectively as
      having unchanged (group 1) or increased (group 2) RDW on the basis of a cut-off
      value of 14.6%. The mean age of patients was 63 +/- 15 years. The mean follow-up
      duration was 11 +/- 7 days, and 21 patients died. Among these 21 patients, 1
      (1.6%) was in group 1 and 20 (27%) were in group 2 (p <0.001). Increased RDW
      >14.6% on admission, age, presence of shock, heart rate, oxygen saturation, and
      creatinine level were found to have prognostic significance in univariate Cox
      proportional-hazards analysis. Only increased RDW >14.6% on admission (hazard
      ratio 15.465, p = 0.012) and the presence of shock (hazard ratio 9.354, p <0.001)
      remained associated with increased risk for acute PE-related early mortality in a
      multivariate Cox proportional-hazards model. In conclusion, high RDW was
      associated with worse hemodynamic parameters, and RDW seems to aid in the risk
      stratification of patients with acute PE.

PMID- 21958742
TI  - Presentation in patients with angiographically documented coronary artery disease
      and type II diabetes mellitus (from the BARI 2D Clinical Trial).
AB  - Clinically stable patients with type 2 diabetes mellitus and coronary artery
      disease are not often thought to present with the symptom of typical angina. The
      aims of this study were to enumerate the proportion of patients presenting with
      typical angina or other cardiac symptoms and to elucidate what important clinical
      variables are associated with the presence of typical angina in patients with
      type 2 diabetes mellitus and angiographically documented coronary artery disease.
      Symptoms of angina, anginal equivalents, or an absence of symptoms were obtained
      using baseline data from the Bypass Angioplasty Revascularization Investigation 2
      Diabetes (BARI 2D) trial (n = 2,319). A bivariate analysis stratified by the
      presence or absence of previous revascularization and logistic regression
      modeling with a stepwise covariate selection was used. Eighty-two percent of
      patients had symptoms, while 18% presented asymptomatically. This was further
      divided approximately into typical angina (1/5), anginal equivalents (1/5),
      combination (2/5), and asymptomatic (1/5). A history of previous
      revascularization was a determinant of the type of symptom presentation with
      regard to the variables gender, age, current insulin use, myocardial jeopardy
      index score, and use of beta blockers. In the multivariate logistic regression
      analysis, of the available candidate variables, only a history of beta-blocker
      use (odds ratio 1.53, 95% confidence interval 1.24 to 1.94, p <0.0001) and
      previous percutaneous coronary intervention (odds ratio 1.55, 95% confidence
      interval 1.24 to 1.94, p <0.0001) had higher odds of an association with typical
      angina. In conclusion, a large proportion of patients with type 2 diabetes
      mellitus and coronary artery disease indeed have symptoms. Future studies of long
      term outcomes associated with these symptoms are needed.

PMID- 21958743
TI  - Postlobectomy chest radiographic changes: a quantitative analysis.
AB  - PURPOSE: To provide a quantitative analysis of postlobectomy chest radiographic
      changes and to evaluate whether the scarring from prior sternotomy affects the
      size of the hemithorax and the duration of air leak in patients with subsequent
      lobectomy. METHODS: In this retrospective case-controlled series, 10 consecutive
      patients who had a lobectomy after a prior sternotomy and 30 controls, 3 for each
      case, matched for lobectomy site were identified. Pre- and postoperative chest
      radiographs were quantitatively analysed for diaphragmic elevation, size of each
      hemithorax, mediastinal shift, and the presence of pneumothorax. Charts were
      reviewed for air-leak duration, surgical complications, and duration of
      hospitalization. RESULTS: There was no difference between patients with lobectomy
      and with and without prior sternotomy for the following variables expressed as
      mean (SD): hemidiaphragm elevation (1.5 +/- 2.5 vs 0.5 +/- 2.0 cm; P = .2),
      change of hemithorax size (mean transverse, 0.99 +/- 0.05 vs 0.97 +/- 0.07; P =
      .5; craniocaudal, 0.93 +/- 0.08 vs 0.91 +/- 0.08; P = .4) and mediastinal shift
      (upper, 1.2 +/- 0.4 vs 1.3 +/- 0.6; P = .5; lower, 1.2 +/- 0.4 vs 1.2 +/- 0.3; P
      = .8), the latter 2 were expressed as the ratio of post- to preoperative
      measurements. These postlobectomy radiographic findings varied, depending on the
      resected lobe, and became progressively more pronounced during the first 12
      months after surgery. There was no difference in pneumothorax duration (mean
      [SD]) (9.5 +/- 21 days vs 6.4 +/- 7.5 days; P = .5), air leak duration (mean
      [SD]) (0.7 +/- 0.8 days vs 1.3 +/- 3.9 days; P = .6), complication rate (20% vs
      30%; P = .5), or hospital stay (mean [SD]) (6.0 +/- 1.7 days vs 6.9 +/- 4.7 days;
      P = .6). CONCLUSION: There are specific patterns of volume loss, mediastinal
      shift, and hemidiaphragm displacement that can be quantified on postlobectomy
      chest radiographs. Prior sternotomy did not affect postlobectomy radiographic
      changes or patient outcome.

PMID- 21958744
TI  - Retromer regulates apical-basal polarity through recycling Crumbs.
AB  - Epithelial cells are characterized by an "apical-basal" polarization. The
      transmembrane protein Crumbs (Crb) is an essential apical determinant which
      confers apical membrane identity. Previous studies indicated that Crb did not
      constantly reside on the apical membrane, but was actively recycled. However, the
      cellular mechanism(s) underlying this process was unclear. Here we showed that in
      Drosophila, retromer, which was a retrograde complex recycling certain
      transmembrane proteins from endosomes to trans-Golgi network (TGN), regulated Crb
      in epithelial cells. In the absence of retromer, Crb was mis-targeted into
      lysosomes and degraded, causing a disruption of the apical-basal polarity. We
      further showed that Crb co-localized and interacted with retromer, suggesting
      that retromer regulated the retrograde recycling of Crb. Our data presented here
      uncover the role of retromer in regulating apical-basal polarity in epithelial
      cells and identify retromer as a novel regulator of Crb recycling.

PMID- 21958745
TI  - The forkhead transcription factor FoxB1 regulates the dorsal-ventral and anterior
      posterior patterning of the ectoderm during early Xenopus embryogenesis.
AB  - The formation of the dorsal-ventral (DV) and anterior-posterior (AP) axes,
      fundamental to the body plan of animals, is regulated by several groups of
      polypeptide growth factors including the TGF-beta, FGF, and Wnt families. In
      order to ensure the establishment of the body plan, the processes of DV and AP
      axis formation must be linked and coordinately regulated. However, the molecular
      mechanisms responsible for these interactions remain unclear. Here, we
      demonstrate that the forkhead box transcription factor FoxB1, which is
      upregulated by the neuralizing factor Oct-25, plays an important role in the
      formation of the DV and AP axes. Overexpression of FoxB1 promoted neural
      induction and inhibited BMP-dependent epidermal differentiation in ectodermal
      explants, thereby regulating the DV patterning of the ectoderm. In addition,
      FoxB1 was also found to promote the formation of posterior neural tissue in both
      ectodermal explants and whole embryos, suggesting its involvement in embryonic AP
      patterning. Using knockdown analysis, we found that FoxB1 is required for the
      formation of posterior neural tissues, acting in concert with the Wnt and FGF
      pathways. Consistent with this, FoxB1 suppressed the formation of anterior
      structures via a process requiring the function of XWnt-8 and eFGF.
      Interestingly, while downregulation of FoxB1 had little effect on neural
      induction, we found that it functionally interacted with its upstream factor Oct
      25 and plays a supportive role in the induction and/or maintenance of neural
      tissue. Our results suggest that FoxB1 is part of a mechanism that fine-tunes,
      and leads to the coordinated formation of, the DV and AP axes during early
      development.

PMID- 21958746
TI  - Comparison of ruminant and human attaching and effacing Escherichia coli (AEEC)
      strains.
AB  - The presence of 12 genes associated with virulence in human attaching and
      effacing Escherichia coli (AEEC) was studied within a collection of 20
      enterohemorrhagic E. coli (EHEC) and 206 atypical enteropathogenic E. coli (EPEC)
      isolated from ruminants. In addition, virulence genes and the clonal relationship
      of 49 atypical EPEC O26 strains isolated from humans and ruminants were compared
      to clarify whether ruminants serve as a reservoir of atypical EPEC for humans. A
      great diversity in the content of virulence gene was found. Thus, the espH, espG
      and map genes were detected in more than 85% of ruminant AEEC strains; the tccP2,
      espI, efa1/lifA, ehxA and paa genes were present in 50-70% of strains; and other
      genes such as tccP, espP, katP and toxB were detected in <25% of strains. EHEC
      strains contained more virulence genes than atypical EPEC strains. Our results
      suggest for the first time that the efa1/lifA gene is associated with diarrhea in
      newborn ruminants and that the AEEC strains with the H11 flagellar antigen are
      potentially more virulent than the non-H11 AEEC strains. Importantly, we
      identified a new intimin variant gene, eaerho, in three ruminant atypical EPEC
      strains. The comparison of ruminant and human EPEC O26 strains showed that some
      ruminant strains possess virulence gene profiles and pulse-field gel
      electrophoresis pulsotypes similar to those of human strains. In conclusion, our
      data suggest that atypical EPEC is a heterogeneous group with different
      pathogenic potential and that ruminants could serve as a reservoir of atypical
      EPEC for humans.

PMID- 21958747
TI  - Antagonistic effect of indigenous skin bacteria of brook charr (Salvelinus
      fontinalis) against Flavobacterium columnare and F. psychrophilum.
AB  - Industrial fish production exposes fish to potentially stressful conditions,
      which in turn may induce infections by opportunistic pathogens. Probiotics appear
      to be a promising way to prevent opportunistic infections in aquaculture. In this
      study, we tested the inhibitory potential of endogenous bacterial communities
      found in the mucus of brook charr (Salvelinus fontinalis) against two major
      pathogens Flavobacterium columnare and Flavobacterium psychrophilum. Nine
      bacterial strains were isolated from brook charr skin mucus and tested for
      potential antagonistic activity. Results from both agar diffusion assays and
      broth co-culture assays showed the presence of antagonism. We identified seven
      bacterial strains, collected from unstressed fish, which exerted strong
      antagonism against F. psychrophilum and/or F. columnare. These strains were mixed
      and used to treat columnaris disease in an in vivo experiment in which four
      distinct fish families were tested. This treatment resulted in a decrease of
      mortality (54-86%) across fish families indicating that candidates from the host
      microbiota are potentially suitable for probiotic development. This would allow
      for the efficient (ability to adhere and colonize the host mucus) and durable
      management (antagonistic effect against pathogens which would be harmless for the
      host and safe for its environment) of opportunistic diseases in aquaculture.

PMID- 21958748
TI  - Antimicrobial activity of marine sponges against coagulase-negative staphylococci
      isolated from bovine mastitis.
AB  - Bovine mastitis remains worldwide a major challenge for the dairy industry
      despite the widespread implementation of control strategies. The increasing
      number of coagulase-negative staphylococci (CNS) causing mastitis and of bacteria
      resistant to conventional antibiotics has become a serious problem in recent
      years. Marine sponges are a rich source of bioactive compounds, and many species
      can be useful for the development of new antimicrobial drugs. In the present
      study, 49 CNS strains were isolated from bovine mastitis cases from 21 different
      dairy herds kept at farms in Southeast Brazil. Strains were analyzed for
      antimicrobial susceptibility and mecA gene detection. Fifty-nine percent of the
      CNS strains were resistant to at least one of the drugs tested and 12.2% were
      classified as multiresistant. Three strains carried the mecA gene, confering
      resistance to the beta-lactamic antibiotics. In addition, the CNS strains were
      submitted to in vitro screening for antimicrobial activities of extracts from
      marine sponges. Extracts from the sponge species Cinachyrella sp., Haliclona sp.
      and Petromica citrina showed antibacterial activity against 61% of the CNS
      strains, including strains resistant to conventional antibiotics. Extracts from
      P. citrina showed the largest spectrum of inhibitory activity. The aqueous
      extract inhibited 51% of the CNS strains and presented a bactericidal effect over
      susceptible and multiresistant-bacteria at a minimal inhibitory concentration of
      1.024MUg/ml. This study shows the potential of marine sponges as new sources of
      antibiotics and disinfectants for the control of CNS involved in bovine mastitis.

PMID- 21958749
TI  - Isolation, expansion and functional assessment of CD4+CD25+FoxP3+ regulatory T
      cells and Tr1 cells from uremic patients awaiting kidney transplantation.
AB  - BACKGROUND: The immunosuppressive properties of regulatory T cells have emerged
      as an attractive tool for the development of immunotherapies in various disease
      contexts, e.g. to treat transplantation induced immune reactions. This paper
      focuses on the process of obtaining and functionally characterizing
      CD4+CD25+FoxP3+ regulatory T cells and Tr1 cells from uremic patients awaiting
      kidney transplantation. METHODS: From October 2010 to March 2011 uremic patients
      awaiting living donor kidney transplantation, and their corresponding kidney
      donors, were enrolled in the study. A total of seven pairs were included.
      Isolation of CD4+CD25+FoxP3+ regulatory T cells was performed by magnetic
      activated cell sorting of peripheral blood mononuclear cells obtained from the
      uremic patients. Donor specific Tr1 cells were differentiated by repetitive
      stimulation of immature CD4+ T cells with immature dendritic cells, with the T
      cells coming from the future kidney recipients and the dendritic cells from the
      corresponding kidney donors. Cells were then expanded and functionally
      characterized by the one-way mixed leukocyte reaction and assessment of IL-10
      production. Phenotypic analysis was performed by flow cytometry. RESULTS: The
      fraction of CD4+CD25+FoxP3+ regulatory T cells after expansion varied from 39.1
      to 50.4% and the cells retained their ability to substantially suppress the mixed
      leukocyte reaction in all but one patient (3.8-19.2% of the baseline stimulated
      leukocyte activity, p<0.05). Tr1 cells were successfully differentiated from all
      but one patient and produced high levels of IL-10 when stimulated with immature
      dendritic cells (1,275-11,038% of the baseline IL-10 secretion, p<0.05).
      CONCLUSION: It is practically feasible to obtain and subsequently expand
      CD4+CD25+FoxP3+ regulatory T cells and Tr1 cells from uremic patients without
      loss of function as assessed by in vitro analyses. This forms a base for adoptive
      regulatory T cell therapy in the setting of living donor kidney transplantation.

PMID- 21958750
TI  - Testing the norm to fat talk for women of varying size: what's weight got to do
      with it?
AB  - "Fat talk" is the conversational phenomenon whereby people berate their bodies in
      social circles. This study assessed whether norms of fat talk differ for
      overweight versus average-weight women. Sixty-three women read a script depicting
      a fat talk situation during which an overweight or average-weight target woman
      engaged in positive or negative body talk. Regardless of the target's weight,
      participants perceived it to be more typical and less surprising if she engaged
      in negative body talk (fat talk) rather than positive body talk. Furthermore, fat
      talk from either weight group did not affect the likeability of the target, but
      women, overweight or of average weight, who engaged in positive talk were
      perceived to have more socially desirable personality characteristics.

PMID- 21958751
TI  - Adrenal venous sampling by using gadopentetate dimeglumine in patients with
      contraindications for iodinated contrast agents.

PMID- 21958752
TI  - Perceval sutureless approach in a patient with porcelain aorta unsuitable for
      transcatheter aortic valve implantation.

PMID- 21958753
TI  - Prevalence and clinical outcomes of left ventricular systolic dysfunction after
      carbon monoxide exposure.

PMID- 21958755
TI  - Nondestructive high-resolution solid-state NMR of rotating thin films at the
      magic-angle.
AB  - We present a new approach to nondestructive magic-angle spinning (MAS) nuclear
      magnetic resonance (NMR) for thin films. In this scheme, the sample put on the
      top of a rotor is spun using the conventional MAS system, and the NMR signals are
      detected with an additional coil. Stable spinning of disk-shaped samples with
      diameters of 7 mm and 12 mm at 14.2 and 7 kHz are feasible. We present 7Li MAS
      NMR experiments of a thin-film sample of LiCoO2 with a thickness of 200 nm.
      Taking advantage of the nondestructive feature of the experiment, we also
      demonstrate ex situ experiments, by tracing conformation change upon annealing
      for various durations. This approach opens the door for in situ MAS NMR of thin
      film devices as well.

PMID- 21958754
TI  - Noncoding RNAs and cancer.
AB  - The study of miRNAs and other noncoding RNAs has revolutionised our
      understanding of gene expression regulation during cancer development and
      progression, creating one of the fastest-growing research fields in cancer with
      realistic therapeutic potential. The 2011 Non-coding RNAs and Cancer Symposium
      hosted by the University College London Cancer Institute focused on the function
      and regulation of noncoding RNAs during oncogenesis.

PMID- 21958756
TI  - Subjective age in early adolescence: relationships with chronological age,
      pubertal timing, desired age, and problem behaviors.
AB  - Subjective age generally refers to the age that one feels. In a cross-sectional
      questionnaire study of 245 adolescents ages 10-14 years, we examined (a) whether,
      and when, a cross-over in subjective age occurs, (b) differences in subjective
      age among pubertal timing groups, (c) correlations between subjective age and
      each of desired age and five problem behaviors, and (d) the relative
      contributions of chronological age, pubertal timing, desired age, and problem
      behaviors to subjective age in boys and girls. Adolescents generally reported
      subjective and desired ages that were slightly older than their chronological
      ages. A cross-over in subjective age occurred at 10.4 years. Late maturing
      adolescents reported relatively younger subjective ages than their early and on
      time maturing peers. For boys, only desired age significantly predicted
      subjective age. For girls, an older desired age, late maturation, and higher
      scores on anxious/depressed feelings, rule-breaking behavior, and aggressive
      behavior significantly predicted older subjective ages.

PMID- 21958757
TI  - Accounting for speed-accuracy tradeoff in perceptual learning.
AB  - In the perceptual learning (PL) literature, researchers typically focus on
      improvements in accuracy, such as d'. In contrast, researchers who investigate
      the practice of cognitive skills focus on improvements in response times (RT).
      Here, we argue for the importance of accounting for both accuracy and RT in PL
      experiments, due to the phenomenon of speed-accuracy tradeoff (SAT): at a given
      level of discriminability, faster responses tend to produce more errors. A formal
      model of the decision process, such as the diffusion model, can explain the SAT.
      In this model, a parameter known as the drift rate represents the perceptual
      strength of the stimulus, where higher drift rates lead to more accurate and
      faster responses. We applied the diffusion model to analyze responses from a yes
      no coherent motion detection task. The results indicate that observers do not use
      a fixed threshold for evidence accumulation, so changes in the observed accuracy
      may not provide the most appropriate estimate of learning. Instead, our results
      suggest that SAT can be accounted for by a modeling approach, and that drift
      rates offer a promising index of PL.

PMID- 21958758
TI  - Intraoperative device closure of atrial septal defects in the older population.
AB  - OBJECTIVE: This study sought to prove the safety and feasibility of
      intraoperative device closure of atrial septal defect (ASD) with transthoracic
      minimal invasion in the older patients. METHODS: From January 2006 to December
      2009, 47 patients aged 50 years or more and suffered from atrial septal defect
      were enrolled in our institution. Patients were divided into two groups, 27 of
      which in group I with intraoperative device closure and the other 20 in group II
      with surgical closure. In group I, the method involved a minimal intercostal
      incision, which was performed after full evaluation of the atrial septal defect
      by transthoracic echocardiography, and the insertion of the device through the
      delivery sheath to occlude the atrial septal defect. RESULTS: In group I,
      implantation was ultimately successful in all patients. The complete closure rate
      at 24 hours and 1 year were 81.5% and 100% respectively. In 6 of 27 patients,
      minor complications occurred: transient arrhythmia (n = 5) and blood transfusion
      (n = 3). In group II, all patients were closured successfully; almost all of them
      needed blood transfusion and suffered from various minor complications though.
      During a follow-up period of 1 to 5 years, no residual shunt, noticeable mitral
      regurgitation, significant arrhythmias, thrombosis, or device failure were found.
      In our comparative studies, group II had significantly longer ICU stay and
      hospital stay than group I (p < 0.05). The cost of group I was less than that of
      group II(p < 0.05). CONCLUSIONS: Minimally invasive transthoracic device closure
      of the atrial septal defect at advanced age with a domestically made device
      without cardiopulmonary bypass is safe and feasible under transthoracic
      echocardiographic guidance. It was cost-savings, yielding better cosmetic results
      and leaving fewer traumas than surgical closure. Early and mid-term results are
      encouraging. However, it is necessary to evaluate the long-term results.

PMID- 21958760
TI  - Lifestyle and nutrition related to male longevity in Sardinia: an ecological
      study.
AB  - BACKGROUND AND AIMS: A demographic analysis in the Mediterranean island of
      Sardinia revealed marked differences in extreme longevity across the 377
      municipalities and particularly identified a mountain inner area where the
      proportion of oldest subjects among male population has one of the highest
      validated value worldwide. The cause(s) of this unequal distribution of male
      longevity may be attributed to a concurrence of environmental, lifestyle and
      genetic factors. METHODS AND RESULTS: In this study we focussed on some lifestyle
      and nutrition variables recorded in the island's population in early decades of
      20th century, when agricultural and pastoral economy was still prevalent, and try
      to verify through ecological spatial models if they may account for the
      variability in male longevity. By computing the Extreme Longevity Index (the
      proportion of newborns in a given municipality who reach age 100) the island's
      territory was divided in two areas with relatively higher and lower level of
      population longevity. Most nutritional variables do not show any significant
      difference between these two areas whereas a significant difference was found
      with respect to pastoralism (P = 0.0001), physical activity estimated by the
      average slope of the territory in each municipality (P = 0.0001), and average
      daily distance required by the active population to reach the usual workplace (P
      = 0.0001). CONCLUSION: Overall, these findings suggest that factors affecting the
      average energy expenditure of male population such as occupational activity and
      geographic characteristics of the area where the population mainly resides, are
      important in explaining the spatial variation of Sardinian extreme longevity.

PMID- 21958759
TI  - Deciphering the role of Th17 cells in human disease.
AB  - Since their identification in 2005, T helper (Th)17 cells have been proposed to
      play important roles in several human diseases, including various autoimmune
      conditions, allergy, the development and progression of tumors, and the
      acceptance or rejection of transplanted organs and bone marrow. Focusing on human
      studies, here we review recent developments regarding Th17 biology and function
      in each of these fields. Th17 cells actively participate in the pathogenesis of
      autoimmune disease, allergy and transplantation rejection. Th17 cells contribute
      to protective antitumor immunity in human epithelial malignancy, whereas Th17
      associated cytokines may also be associated with tumor initiation and growth in
      the context of chronic inflammation and infection. Also discussed is how the in
      vivo plasticity of Th17 cells may be an important feature of Th17 cell biology in
      human disease.

PMID- 21958761
TI  - Must surgeons tell mitral valve repair candidates about a new percutaneous repair
      device that is only available elsewhere?

PMID- 21958762
TI  - Intraoperative factors and the risk of respiratory complications after
      pneumonectomy.
AB  - BACKGROUND: The potential effect of intraoperative factors on respiratory
      complications after pneumonectomy is still unclear. METHODS: We conducted a
      retrospective cohort study; charts of 129 patients who underwent elective
      pneumonectomy at the University of Virginia were reviewed. Logistic regression
      was used to estimate the effect of anesthetic factors on the odds of at least one
      respiratory complication. Linear regression models were fit to assess the impact
      of these outcomes on length of stay (LOS). RESULTS: The incidence of respiratory
      complications in this cohort was 21%. In univariate analysis total nonblood
      fluids (p = 0.001), and the blood products packed red blood cells (p < 0.001),
      plasma (p < 0.001), and platelets (p = 0.044) were significantly associated with
      respiratory complications. In a multivariable logistic regression analysis,
      single unit transfusion of any blood product (packed red blood cells, plasma, or
      platelets) was identified as a major risk factor for respiratory complications
      after controlling for covariates (odds ratio = 1.47, 95% confidence interval 1.06
      to 2.05). Respiratory failure and complications were closely related to LOS,
      increasing the LOS by a factor of 4.7 (95% confidence interval 3.51 to 6.18) and
      3.5 (95% confidence interval 2.69 to 4.41), respectively. CONCLUSIONS: Blood
      product transfusion affects respiratory function and is an independent risk
      factor for respiratory complications after pneumonectomy.

PMID- 21958763
TI  - Invited commentary.

PMID- 21958764
TI  - Pulmonary resection for metastatic adrenocortical carcinoma: the National Cancer
      Institute experience.
AB  - BACKGROUND: Adrenocortical carcinoma (ACC) is a rare neoplasm with a high
      propensity for locoregional recurrences and distant metastases for which there
      are no effective systemic therapies. This study was undertaken to determine
      outcomes of patients undergoing pulmonary metastasectomy for ACC. METHODS: A
      single-institution retrospective review was performed of patients undergoing
      pulmonary metastasectomy for ACC from 1979 to 2010. RESULTS: Twenty-six patients
      underwent 60 pulmonary metastasectomies. Fifteen patients (58%) underwent
      unilateral thoracotomy, 6 (23%) had staged thoracotomies, and 5 (19%) underwent
      median sternotomy as the initial thoracic procedure. Median number and size of
      lesions were 6 and 2 cm, respectively. Twenty-three patients (88%) were rendered
      free of disease in the lung, and 14 (54%) were rendered completely free of
      disease. Median overall and 5-year actuarial survivals from initial pulmonary
      metastasectomy were 40 months and 41%, respectively, with a median potential
      follow-up of 120 months. Median recurrence-free survival (RFS) and 5-year RFS for
      ipsilateral thoracic recurrences were 6 months, and 25%, respectively. The median
      RFS in the contralateral thorax was 5 months. Time to first recurrence after
      adrenalectomy and T stage of the primary tumor, but not adjuvant or neoadjuvant
      chemotherapy, were associated with increased overall survival after pulmonary
      metastasectomy. CONCLUSIONS: This study represents the most comprehensive review
      of outcomes of patients undergoing pulmonary metastasectomy for ACC. Given the
      lack of effective systemic therapies, pulmonary metastasectomy may be beneficial
      in properly selected patients.

PMID- 21958765
TI  - Invited commentary.

PMID- 21958766
TI  - The "rib-like" technique for surgical treatment of sternal tumors: lessons
      learned from 101 consecutive cases.
AB  - BACKGROUND: Sternal tumors represent a rare subgroup of chest wall neoplasms in
      which indication, surgical issues, and long-term results are rarely reported.
      Thus, in this study we reevaluated our experience in sternal replacement from a
      series of 101 consecutive cases during the last 30 years. METHODS: Clinical
      records of patients who underwent sternal resection between January 1980 and
      December 2008 were reviewed. The technique of reconstruction after sternectomy
      varied over time, including mesh replacement in 52 patients (group A), rigid
      prosthesis in 27 patients (group B), and the "rib-like" technique, a semi-rigid
      tridimensional prosthesis reproducing the shape of native ribs, in 22 patients
      (group C). Postoperative outcomes and long-term survival were analyzed. RESULTS:
      Of 101 patients, 42 underwent resection for primary chest wall tumors, 30 for
      breast cancer, 15 for locally advanced tumors, 11 for metastatic disease, and 3
      for benign disease. One patient died postoperatively. The overall major
      complications rate was similar between groups. Local infection required
      prosthetic removal in 7 patients of groups A and B (9%). No infection occurred in
      group C (p = 0.02). Median survival exceeded 60 months for primary sternal tumors
      and 22 months for other cancer (p = 0.01). The worst survival was recorded in
      radioinduced sarcoma (17 months) and in patients who underwent previous resection
      before salvage sternectomy (18 months). CONCLUSIONS: Results from this study
      showed that an adequate sternal resection should be done at the first operation
      and that improving prosthetic integration with surrounding tissues may reduce the
      local complication rate.

PMID- 21958767
TI  - Safety and effectiveness of a new fibrin pleural air leak sealant: a multicenter,
      controlled, prospective, parallel-group, randomized clinical trial.
AB  - BACKGROUND: This study evaluated the sealing capacity and safety of a new fibrin
      sealant (FS) to reduce alveolar air leaks (AALs) after pulmonary resections in a
      randomized controlled clinical trial conducted in 3 Italian centers. METHODS: The
      study randomized (1:1) 185 patients with an intraoperative AAL graded 1 to 3
      according to the Macchiarini scale: 91 received FS and 94 had standard lung
      closure. The primary outcomes were the length of postoperative AAL duration and
      the mean time to chest drain removal. Other end points included the percentage of
      patients without AAL, the development of serum antibodies against bovine
      aprotinin, and any adverse event related to FS. Chest drains were removed when
      fluid output was 100 mL/day or less, with no air leak. RESULTS: The study groups
      were comparable with respect to demographic variables and surgical procedures.
      The FS group showed a statistically significant reduction in duration of
      postoperative AALs (9.52 vs 35.8 hours; p < 0.005) and in the percentage of
      patients with AALs at wound closure (81.11% vs 100%; p < 0.001); the difference
      in time to chest drain removal was not significant. Pleural empyema developed in
      1 patient with FS treatment vs in 4 with standard treatment, and antibodies
      against bovine aprotinin were found in 34 of 91 FS-treated patients. CONCLUSIONS:
      The present study showed that the new FS is safe and effective in preventing AALs
      after lung resections and in shortening the duration of postoperative AALs.

PMID- 21958768
TI  - Invited commentary.

PMID- 21958769
TI  - Effect of prior cardiac operations on survival after coronary artery bypass
      grafting.
AB  - BACKGROUND: We examined a recent regional experience to determine the effect of a
      prior cardiac operation on short-term and midterm outcomes after coronary artery
      bypass grafting (CABG). METHODS: We identified 20,703 patients who underwent
      nonemergent CABG at 8 centers in northern New England from 2000 to 2008, of whom
      818 (3.8%) had undergone prior cardiac operations. Prior CABG using a minimal or
      full sternotomy was considered a prior sternotomy. Survival data out to 4 years
      were obtained from a link with the Social Security Administration Death Index.
      Hazard ratios were estimated using a Cox proportional hazards regression model,
      and adjusted survival curves were estimated using inverse probability weighting.
      In a separate analysis, 1,182 patients were matched 1:1 by a patient's propensity
      for having undergone prior CABG. RESULTS: Patients with prior sternotomies had a
      greater burden of comorbid diseases and increased acuity and had a greater
      likelihood of returning to the operating room for bleeding and low cardiac output
      failure. Prior sternotomy was associated with an increased risk of death out to 4
      years for patients undergoing CABG, with an unmatched hazard ratio of 1.34 (95%
      confidence interval, 1.10 to 1.64) and a matched hazard ratio of 1.36 (95%
      confidence interval, 1.01 to 1.81). CONCLUSIONS: Analyses of our recent regional
      experience with nonemergent CABG showed that a prior cardiac operation was
      associated with a nearly twofold increased hazard of death at up to 4 years of
      follow-up.

PMID- 21958770
TI  - Invited commentary.

PMID- 21958771
TI  - Outcomes associated with bilateral internal thoracic artery grafting: the
      importance of age.
AB  - BACKGROUND: Although bilateral internal thoracic artery (BITA) grafting in
      coronary artery bypass grafting (CABG) is associated with low morbidity and good
      long-term results, controversy exists about the age after which BITA grafting is
      no longer beneficial. We sought to determine if such an age cutoff point exists.
      METHODS: The study cohort consisted of 5,601 consecutive patients from a cardiac
      surgery registry who underwent isolated CABG (1,038 [19%] BITA grafts, 4,029
      [72%] single internal thoracic artery [SITA] grafts, 534 [10%] vein-only grafts)
      between 1995 and 2008. A Cox model was used to compare survival by use of
      bilateral, single, or no internal thoracic artery (ITA) grafts, adjusting for
      baseline clinical and demographic characteristics. RESULTS: Mean follow-up was
      7.1 years. Patients undergoing BITA grafting had the lowest 1-year mortality
      (2.4% versus 4.3% SITA grafting and 8.2% vein-only grafting; p < 0.0001).
      Relative to SITA grafting, a crude survival benefit of 54% existed for BITA
      grafting (hazard ratio [HR] 0.46; 95% confidence interval [CI], 0.37 to 0.57; p <
      0.0001) with worse survival for vein-only grafts (HR, 1.16; 95% CI, 0.99 to 1.37;
      p = 0.07). After adjustment, the benefit of BITA grafting was no longer
      statistically significant (HR, 0.87; 95% CI, 0.69 to 1.08; p = 0.2). However age
      may be an effect modifier: a spline analysis plotting HR (BITA grafting versus
      SITA grafting) against age suggested a potential survival advantage associated
      with BITA grafting in patients younger than 69.9 years. CONCLUSIONS: Bilateral
      internal thoracic artery grafting is a reasonable revascularization strategy in
      suitable patients up to age 70 years. As benefits of arterial grafting become
      more obvious over time, a longer period of follow-up will be needed to confirm
      the advantage of a BITA grafting strategy. In the meantime the BITA grafting
      advantage for patients older than 70 years is not clear.

PMID- 21958772
TI  - Invited commentary.

PMID- 21958773
TI  - Statin therapy and saphenous vein graft disease after coronary bypass surgery:
      analysis from the CASCADE randomized trial.
AB  - BACKGROUND: Current guidelines recommend statin therapy after coronary artery
      bypass grafting (CABG) to attain low-density lipoprotein (LDL) levels less than
      100 mg/dL. Whether achieving LDL levels less than 70 mg/dL improves postoperative
      graft patency remains unknown. METHODS: The CASCADE (Clopidogrel after Surgery
      for Coronary Artery Disease) trial was a randomized study that evaluated the
      addition of clopidogrel to aspirin on the development of saphenous vein graft
      disease after CABG. Patients received the standard of care regarding
      postoperative statin therapy with targeted LDL levels less than 100 mg/dL. Twelve
      months postoperatively, patients returned for a coronary angiogram and saphenous
      vein graft (SVG) intravascular ultrasonogram. In this post hoc analysis, the
      impact of statin therapy on graft patency and vein graft intimal hyperplasia was
      assessed. RESULTS: LDL levels significantly declined over the period of the trial
      (p = 0.002). Twelve months postoperatively, 58.4% patients achieved LDL levels
      less than 70 mg/dL. Twelve-month graft patency was higher for patients with LDL
      levels less than 100 mg/dL (96.5%) compared with patients with LDL levels >100
      mg/dL (83.3%, p = 0.03), even after adjustment in multivariate analysis (odds
      ratio [OR], 5.2; 95% confidence interval [CI], 1.3-21.6; p = 0.02). However, no
      improvement in graft patency was noted with further LDL reduction to less than 70
      mg/dL (p = 1.00). Consistent statin use throughout the trial period was
      independently associated with less vein graft intimal hyperplasia documented by
      intravascular ultrasound at 12 months (p = 0.04). CONCLUSIONS: Statin therapy to
      achieve LDL levels less than 100 mg/dL was independently associated with improved
      graft patency in the CASCADE trial. Randomized clinical trials are warranted to
      prospectively evaluate postoperative LDL reduction to less than 70 mg/dL and its
      impact on graft patency after CABG.

PMID- 21958774
TI  - The patency of sequential and individual vein coronary bypass grafts: a
      systematic review.
AB  - BACKGROUND: Saphenous vein grafts continue to be the backbone of daily coronary
      revascularization practice, but controversy still exists about whether to use
      them as an individual or sequential graft. We undertook a systematic review and
      meta-analysis of cohort studies to compare the midterm or long-term patency of
      sequential vein coronary bypass grafts with those of vein grafts. METHODS: A
      comprehensive search strategy was run in PubMed, Embase, the Cochrane Library,
      and the Chinese Biomedical Literature Database. Inclusion criteria were the
      following: (1) two cohorts of patients received sequential and single saphenous
      vein coronary bypass grafting, respectively; (2) prospective or retrospective
      cohort design; and (3) graft patency examined by angiography or ultrafast
      computed tomography. Two researchers independently performed the literature
      search, data extraction, and quality assessment. RESULTS: We identified 1,385
      titles, reviewed 38 articles for inclusion criteria, and included 12 studies in
      the meta-analysis. The risk of occlusion in sequential grafts was lower (risk
      ratio [RR] = 0.67, 95% confidence interval [CI] 0.60 to 0.74) than that in single
      grafts. The risk of occlusion in side-to-side anastomoses was lower (RR = 0.52;
      95% CI, 0.34 to 0.80) than that of end-to-side anastomoses for sequential vein
      grafts. There was no difference in occlusion between the distal end-to-side
      anastomoses of sequential vein grafts and those of single vein grafts (RR = 0.85;
      95% CI, 0.68 to 1.06). CONCLUSIONS: The midterm and long-term patency of
      sequential vein grafts appears to be better than that of single vein grafts and
      the patency of side-to-side anastomoses appears to be better than that of end-to
      side anastomoses for sequential vein grafts.

PMID- 21958775
TI  - Endothelium-dependent vasoconstriction in isolated vessel grafts: a novel
      mechanism of vasospasm?
AB  - BACKGROUND: YC-1 (3-(5'-hydroxymethyl-2'furyl)-1-benzyl-indazole) is an
      allosteric activator of soluble guanylyl cyclase (sGC) and a vasodilator. This
      study describes a paradoxical action of YC-1 in isolated vessels of patients with
      coronary artery disease (CAD) that appears to trigger an endothelium-dependent
      vasoconstrictor pathway present in vessels with endothelial dysfunction. METHODS:
      Effects of YC-1 on the tensions of isolated vessels were investigated in an organ
      bath. Vasoconstrictors released from the vessels were quantified through enzyme
      linked immunosorbent assay. RESULTS: YC-1 elicited long-lasting constriction in
      saphenous veins and radial arteries from patients with CAD, but not in human
      umbilical veins. The half-maximal effective dose was 1.0 MUmol/L. Constriction
      was attenuated by nifedipine (an L-type Ca(2+)-channel blocker), bosentan (an
      endothelin [ET](A)/ET(B) inhibitor), BQ-788 (N-[(cis-2,6-Dimethyl-1
      piperidinyl)carbonyl]-4-methyl-L-leucyl-1-(methoxycarbonyl)-D-tryptophyl-D
      norleucine; an ET(B) inhibitor), and by denuding, but not by ODQ (1H
      (1,2,4)oxadiazolo[4,3-a]quinoxalin-1-one; an inhibitor of sGC), BQ-123 (cyclo(-D
      Trp-D-Asp-Pro-D-Val-Leu); an ET(A) inhibitor), or phosphoramidon (an endothelin
      converting enzyme inhibitor). Indomethacin (an inhibitor of cyclooxygenase-1 and 
      2) and SQ29,548 ([1S-[1alpha,2alpha(Z),3alpha,4alpha]]-7-[3-[[2
      [(phenylamino)carbonyl]hydrazino]methyl]-7-oxabicyclo[2.2.1]hept-2-yl]-5
      heptenoic acid; a thromboxane receptor antagonist) suppressed YC-1-induced
      constriction, whereas DFU (5,5-dimethyl-3-(3-fluorophenyl)-4-(4
      methylsulfonyl)phenyl-2(5H)-furanone; a cyclooxygenase-2 inhibitor) had no
      effect. Rings of saphenous vein released significantly more endothelin-1 in the
      presence than in the absence of YC-1. CONCLUSIONS: YC-1-induced vasoconstriction
      demonstrates the existence of an endothelium-dependent vasoconstrictor pathway in
      the blood vessels of patients with CAD that to date has been described only in
      animal models of hypertension. Patients with CAD who have elevated plasma levels
      of endothelin-1 are thus prone to endothelium-dependent vasoconstriction, which
      may also play a role in vasospasm in vascular grafts.

PMID- 21958776
TI  - Invited commentary.

PMID- 21958777
TI  - Ten years of clinical results with a tissue-engineered pulmonary valve.
AB  - BACKGROUND: This study was performed to collect prospective safety and
      effectiveness data from a tissue-engineered heart valve implanted for
      reconstruction of the right ventricular outflow tract during the Ross operation.
      METHODS: From May 2000 until June 2002, 11 consecutive patients, mean age 39.6 +/
      10.3 years, received a tissue-engineered heart valve (additive and logistic
      European System for Cardiac Operative Risk Evaluation, respectively, 3.3 +/- 1.3
      and 2.8% +/- 1.4%). Two to four weeks prior to the Ross operation a piece of
      forearm vein or saphenous vein was harvested to isolate, characterize, and expand
      endothelial cells. A cryopreserved pulmonary allograft was decellularized,
      coated, and seeded with autologous vascular endothelial cells, using a specially
      developed bioreactor. Cell seeding density was 1.1 * 10(5) +/- 0.5 * 10(5)
      cells/cm(2) with a viability of 93.2% +/- 2.1%. RESULTS: All patients survived
      surgery. Postoperatively no fever of unknown origin was evident. Currently all
      patients are in New York Heart Association class I. Evaluation of the tissue
      engineered heart valve by transthoracic echocardiography showed a mean pressure
      gradient of 5.4 +/- 2.0 mm Hg at 10 years. Multislice computed tomography showed
      no calcification up to 10 years. CONCLUSIONS: Tissue-engineered heart valves
      showed excellent hemodynamic performance and may prevent degeneration during long
      term follow-up.

PMID- 21958778
TI  - Invited commentary.

PMID- 21958779
TI  - Analysis of survival in 300 high-risk patients up to 2.5 years after transapical
      aortic valve implantation.
AB  - BACKGROUND: Midterm results after transapical aortic valve implantation are still
      unknown in a large group of patients. We report our institutional experience in
      300 high-risk patients. METHODS: Since April 2008, transapical aortic valve
      implantation was performed in 300 patients (mean age, 80 +/- 8 years). The mean
      logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) was
      39% +/- 19% and the mean Society of Thoracic Surgeons (STS) score was 19% +/-
      16%. Eighteen patients were in cardiogenic shock preoperatively. Follow-up was up
      to 31 months with a total of 3,500 months of follow-up. RESULTS: Technical
      success of the procedure was 99.7% (299 of 300 patients). The 30-day mortality
      rate in all patients without cardiogenic shock was 3.9%. The overall 30-day
      mortality for the whole group of 300 patients was 4.7%. The mortality of the last
      100 patients dropped to 2.0%. The cumulative survival was 83% at 1 year, 76% at
      1.5 years, and 65% at 2 years and beyond. In patients with lower risk scores,
      cumulative survival reached 78% at 2 years and beyond. CONCLUSIONS: The outcome
      of transapical aortic valve implantation in very high-risk patients was very
      favorable not only early after the procedure but also later on. Preoperative risk
      scores were not indicators for early mortality but were for later mortality.
      Survival was mainly influenced by noncardiac (renal, pulmonary, and vascular)
      comorbidities as well as by signs of advanced cardiac failure.

PMID- 21958780
TI  - Magnetic resonance investigation of blood flow after aortic valve bypass
      (apicoaortic conduit).
AB  - BACKGROUND: Aortic valve bypass (AVB, apicoaortic conduit) is an alternative to
      aortic valve replacement (AVR) for high-risk patients with aortic stenosis (AS).
      The redistribution of blood flow after AVB has been poorly characterized. In
      order to understand cardiovascular physiology after AVB, we performed cardiac
      magnetic resonance (CMR) imaging of AVB recipients. METHODS: Fifteen patients
      with symptomatic AS underwent beating-heart AVB. Electrocardiography-gated two
      dimensional phase-contrast velocity mapping CMR imaging was conducted on each
      patient. Instantaneous flow was acquired at discrete intervals within the cardiac
      cycle and ventricular function and volumes were evaluated. Five age-matched
      patients without aortic valve disease served as controls. RESULTS: Conduit flow
      (as a percent of total cardiac output) was 65% +/- 5%. Ejection fraction was
      unchanged compared with before AVB (50% +/- 17% versus 57% +/- 13%; p = 0.91).
      Ventricular volumes and cardiac indices were within normal limits and similar to
      those values in controls (cardiac index 2.9 +/- 1.0 versus 2.3 L/min/m(2); p =
      0.26; end-diastolic volume index 59 +/- 17 mL versus 55 +/- 20 mL; p = 0.66; end
      systolic volume index, 25 +/- 12 versus 25 +/- 18 mL; p = 0.91; stroke volume
      index, 33 +/- 11 versus 30 +/- 6 mL; p = 0.57 for AVB and control patients,
      respectively). There was a small degree of retrograde blood flow in the
      descending aorta above the level of the conduit insertion (10% +/- 8% of cardiac
      output). CONCLUSIONS: Aortic valve bypass results in a predictable blood flow
      distribution between the native aorta and conduit and is associated with normal
      ventricular volumes and function.

PMID- 21958781
TI  - Minimally invasive valve surgery with antegrade perfusion strategy is not
      associated with increased neurologic complications.
AB  - BACKGROUND: A Society of Thoracic Surgeons' publication recently associated
      "minimally invasive" approaches with increased neurologic complications; this
      proposed association was questionable due to imprecise definitions. To critically
      reevaluate this issue, we reviewed a large minimally invasive valve experience
      with robust definitions. METHODS: From November 1995 to January 2007, 3,180
      isolated, non-reoperative valve operations were performed; 1,452 (45.7%) were
      aortic replacements and 1,728 (54.3%) were mitral valve procedures. Surgical
      approach was standard sternotomy (28%) or minimally invasive technique (72%).
      Antegrade arterial perfusion was used in 2,646 (83.2%) patients and retrograde
      perfusion in 534 (16.8%). Aortic clamping was direct in 83.4%, with endoclamp in
      16.4% and no clamp in 0.2%. Patients were prospectively followed in a proprietary
      database and the New York State Cardiac Surgery Reporting System (mandatory,
      government audited). A neurologic event was defined as a permanent deficit, a
      transient deficit greater than 24 hours, or a new lesion on cerebral imaging.
      RESULTS: Hospital mortality for aortic valve replacement was 4.0% (sternotomy
      [5.1%] versus minimally invasive [3.4%] p = 0.13); for mitral procedures it was
      2.4% (sternotomy [4.8%] versus minimally invasive [1.8%] p = 0.001). Multivariate
      analysis revealed that age, female gender, renal disease, ejection fraction less
      than 0.30, chronic obstructive pulmonary disease, and emergent operation were
      risk factors for mortality. Stroke occurred in 71 patients (2.2%) (sternotomy
      [2.1%] versus minimally invasive [2.3%] p = 0.82). Multivariate analysis of
      neurologic events revealed that cerebrovascular disease, emergency procedure, no
      clamp, and retrograde perfusion were risk factors. In patients 50 years old or
      younger (n = 662), retrograde perfusion had no significant impact on neurologic
      events (1.6% vs 1.1%, p = 0.57). CONCLUSIONS: A minimally invasive approach with
      antegrade perfusion does not result in increased neurologic complications.
      Retrograde perfusion, however, is associated with increased neurologic risk in
      older patients.

PMID- 21958782
TI  - Cardiomyocyte apoptosis after antegrade and retrograde cardioplegia during aortic
      valve surgery.
AB  - BACKGROUND: Retrograde delivery is associated with inadequate perfusion of
      cardioplegia to all regions of the heart, but the effects on cardiomyocyte death
      and functional outcome remain unknown. We compared antegrade and retrograde
      cardioplegia in a randomized clinical trial to see whether it has effect on
      cardiomyocyte apoptosis and left ventricular function. METHODS: Patients
      underwent elective aortic valve replacement surgery due to aortic valve stenosis.
      They were randomly allocated to receive antegrade (n = 10) or retrograde (n = 10)
      cardioplegia. Apoptotic cardiomyocytes (terminal transferase-mediated dUTP nick
      end labeling, caspase activation) and RNA levels of apoptosis-regulating proteins
      were studied in transmyocardial biopsies obtained before and after the operation.
      Magnetic resonance imaging and transesophageal echocardiography were performed,
      and cardiac enzymes were measured. RESULTS: Clinical outcome and cardiac enzyme
      release were comparable between the groups. Cardiomyocyte apoptosis was
      significantly increased (terminal transferase-mediated dUTP nick end labeling) in
      the left ventricle after the operation in the retrograde, but not in the
      antegrade group (respectively, 0.00% [0.039%] versus 0.092% [0.205%], p = 0.01;
      and 0.00% [0.00%] versus 0.023% [0.054%], p = 0.14). Expression of apoptosis
      regulating proteins BAX, BAD, and BCL-2 were comparable between groups. By
      transesophageal echocardiography, the systolic mitral annulus movement was
      decreased immediately after the operation in the retrograde group. By magnetic
      resonance imaging, the left ventricle mass index was reduced preoperatively to 9
      months postoperatively in the antegrade group. CONCLUSIONS: In contrast to
      antegrade cardioplegia, retrograde cardioplegia is associated with increased
      cardiomyocyte apoptosis, impaired immediate postoperative systolic function, and
      lack of long-term favorable left ventricle remodeling after aortic valve
      replacement, suggesting inadequate myocardial protection.

PMID- 21958783
TI  - Mitral valve replacement is a viable alternative to mitral valve repair for
      ischemic mitral regurgitation: a case-matched study.
AB  - BACKGROUND: Comparisons of mitral valve repair with mitral valve replacement for
      ischemic mitral regurgitation (IMR) have been limited by differences in
      preoperative and operative characteristics of patients undergoing these two types
      of surgical treatment. We performed a propensity-based, case-matched analysis to
      examine whether patients who undergo mitral valve repair and those who undergo
      mitral valve replacement for IMR have similar long-term outcomes. METHODS: We
      compared 65 patients who underwent mitral valve replacement for IMR between 2001
      and 2010 with 65 patients who underwent mitral repair during the same period on
      the basis of age, concomitant coronary bypass grafting, gender, left ventricular
      function, preoperative pulmonary hypertension, and urgency of operation. Mitral
      replacement involved preservation of the subvalvular apparatus. The mean study
      follow-up period was 2.5 +/- 2.1 years. RESULTS: Two patients who underwent
      mitral valve repair died at 30 days postoperatively and three patients died after
      valve replacement. Late survival was the same in the two groups (p = 0.4).
      Recurrent mitral regurgitation (MR) (grade 2+ or higher) at late follow-up was
      observed in 15 patients (23%) after repair; however, only 1 patient (2%) had MR
      with a grade of more than 2+. Mitral valve repair was more commonly associated
      with recurrent MR (grade 2+ or higher) than was mitral valve replacement (p =
      0.04). Patients in both groups had similar freedom from valve-related
      complications and similar left ventricular function at follow-up (both p > 0.2).
      CONCLUSIONS: Mitral valve replacement remains a viable option for the treatment
      of IMR. Although mitral valve repair effectively protects against persistent or
      recurrent moderate-to-severe MR, mitral valve replacement provides better freedom
      from mild-to-moderate MR in this population, with a low incidence of valve
      related complications. Notably, there was no significant difference in left
      ventricular function between the valve-repair and valve-replacement groups at
      follow-up.

PMID- 21958784
TI  - Invited commentary.

PMID- 21958785
TI  - Invited commentary.

PMID- 21958786
TI  - A comparison of outcome in patients with preoperative atrial fibrillation and
      patients in sinus rhythm.
AB  - BACKGROUND: Approximately 10% to 15% of patients undergoing cardiac operations
      suffer from atrial fibrillation (AF) at the time of surgery. The current risk
      stratification methods do not include preoperative arrhythmias. The aim of this
      study was to assess the effect of preoperative AF on the immediate postoperative
      outcome of patients undergoing cardiac surgery as well as in the midterm and long
      term outcomes. METHODS: We reviewed patient data for our institution for a 10
      year period; a total of 14,320 patients undergoing any cardiac operation were
      included; 12,395 (86.5%) had sinus rhythm preoperatively and 1,925 (13.5%) were
      in persistent AF. After propensity matching and adjusting for the preoperative
      and operative characteristics, 1,800 patients remained in each group and were
      compared. RESULTS: Before and after adjusting for the preoperative and operative
      characteristics, inotropic support, ventilation time, renal failure, stroke, and
      surgical wound infection rates were all significantly higher for the patients
      with AF (p < 0.001). Intensive care unit stay and hospital stay as well as in
      hospital mortality were also significantly higher among the patients with AF
      compared with the sinus rhythm group (p < 0.001). At 30 days, 5-year and 10-year
      mortality rates in the AF group were significantly higher compared with those in
      sinus rhythm group (p < 0.001). CONCLUSIONS: Atrial fibrillation preoperatively
      is associated with a higher incidence of postoperative complications. This
      arrhythmia is an important variable that appears to have been excluded from the
      current risk stratification systems. Our experience suggests that AF should be
      considered in the development/update of risk-stratifying methodologies to improve
      the predictive accuracy.

PMID- 21958787
TI  - Invited commentary.

PMID- 21958788
TI  - Left atrial ablation versus biatrial ablation in the surgical treatment of atrial
      fibrillation.
AB  - BACKGROUND: The purpose of this study was to compare the clinical and rhythm
      outcomes between left atrial ablation and biatrial ablation in patients with
      atrial fibrillation-associated mitral valve diseases. METHODS: Data were
      collected on 284 patients who underwent left atrial ablation (n = 85) or biatrial
      ablation (n = 199) of atrial fibrillation using a cryoablation system combined
      with mitral operation from 2006 through 2009. Outcomes were compared using a
      propensity score study design based on 20 baseline patient characteristics.
      RESULTS: In baseline characteristics, patients in the biatrial group were more
      likely to have higher risk clinical and echocardiographic profiles than patients
      in the left atrial group. There were 2 early deaths (0.7%), 1 in each group, and
      5 cases of permanent pacemaker implantation (1.8%) only in the biatrial group.
      Follow-up was complete in 95.1% (n = 270). During a mean follow-up duration of
      26.0 +/- 13.3 months, there were 12 late deaths (1 in the left atrial group, 11
      in the biatrial group). Cumulative incidence of atrial fibrillation in the
      absence of antiarrhythmic medications at 2 years was 25.9% +/- 5.8% in the left
      atrial group and 14.3% +/- 2.8% in the biatrial group (adjusted hazard ratio
      3.06, 95% confidence interval: 1.41 to 6.66, p = 0.005). Major adverse events
      included stroke in 1, cardiac reoperation in 3, and anticoagulation-related
      hemorrhages in 16, infective endocarditis in 1, and mechanical valve thrombosis
      in 1, with no significant intergroup differences in major event-free survival
      rate (p = 0.73). CONCLUSIONS: Compared with left atrial ablation, biatrial
      ablation was more effective in restoration and maintenance of sinus rhythm
      without increasing the risk of postoperative complications.

PMID- 21958789
TI  - Continuous flow left ventricular assist device outcomes in commercial use
      compared with the prior clinical trial.
AB  - BACKGROUND: A multicenter clinical trial conducted from 2005 to 2008 of a
      continuous flow left ventricular assist device (LVAD) resulted in Food and Drug
      Administration approval for bridge to transplantation. The purpose of this
      analysis was to determine changes in posttrial outcomes in widespread commercial
      use since the clinical trial. METHODS: We compared outcomes of 486 patients who
      received a continuous flow LVAD as a bridge to transplantation at 36 centers
      during the clinical trial (March 2005 to April 2008) with outcomes of 1,496
      posttrial patients who received a continuous flow LVAD at 83 centers (April 2008
      to September 2010 as reported to the Interagency Registry for Mechanically
      Assisted Circulatory Support). RESULTS: Baseline data were comparable between
      groups. Cumulative follow-up was 511 and 1,082 patient-years for trial and
      posttrial patients, respectively, and average support duration was 12.6 +/- 14.0
      and 8.7 +/- 7.1 months. Kaplan-Meier survival improved at 1 year from 76% (trial)
      to 85% (posttrial). The percentage of patients undergoing transplantation in the
      first year decreased from 48% in the trial period to 39% in the posttrial period.
      Quality of life metrics improved by 3 months in both groups. CONCLUSIONS: The
      survival rate of a large group of continuous flow LVAD patients in a real-world
      setting after Food and Drug Administration market approval for bridge to
      transplantation has improved since the clinical trial. These data show that
      excellent outcomes have been maintained with dissemination of new LVAD technology
      from a clinical trial phase to more broad based use in the period after market
      approval.

PMID- 21958790
TI  - Clinical impact of concomitant tricuspid valve procedures during left ventricular
      assist device implantation.
AB  - BACKGROUND: Almost 50% of patients referred for implantable left ventricular
      assist device (LVAD) have significant tricuspid regurgitation (TR). Preoperative
      TR is associated with negative outcomes but the clinical benefit of concomitant
      tricuspid valve procedures has not been extensively studied. METHODS: One hundred
      fifteen patients, undergoing implantable LVADs, were identified as having
      significant TR by echocardiography prior to their surgical procedure. Patients
      underwent either LVAD alone (n = 81) versus LVAD plus concomitant tricuspid
      procedures (n = 34) (29 annuloplasty ring repairs and 5 bioprosthetic
      replacements.) Preoperative characteristics and hemodynamics, as well as TR
      severity and clinical outcomes were retrospectively determined from chart and
      database review and compared for the two groups. RESULTS: Preoperative
      characteristics and hemodynamics were similar for the two groups. Postoperative
      TR was markedly reduced for the group undergoing concomitant procedures versus
      LVAD alone. A temporary right ventricular assist device was required for only one
      of the 34 cases in which concomitant tricuspid procedures were performed; for
      patients undergoing LVAD alone, 8 of 81 required right ventricular assist
      devices. Mean duration of postoperative inotrope utilization was increased for
      the LVAD alone group versus the group with concomitant tricuspid procedures (10.0
      vs 8.0 days, respectively, p = 0.04). The incidence of postoperative renal
      dysfunction was increased for the LVAD alone group (39%) versus concomitant
      procedures (21%) (p = 0.05). The LVAD alone group also had a greater mean
      postimplant length of hospitalization versus the concomitant procedures group
      (26.0 vs 19.0 days, p = 0.02). Finally, there was a trend toward improved
      survival for the group with concomitant tricuspid procedures versus LVAD alone.
      CONCLUSIONS: For patients with significant TR undergoing implantable LVAD
      procedures, concomitant tricuspid procedures are associated with improved early
      clinical outcomes.

PMID- 21958791
TI  - Obese patients and mechanical circulatory support: weight loss, adverse events,
      and outcomes.
AB  - BACKGROUND: Obesity and heart failure are increasingly common, but the outcomes,
      weight changes, and adverse events of patients with advanced heart failure and
      obesity on mechanical support is not well described. METHODS: We retrospectively
      reviewed all non-underweight patients with durable mechanical support at a single
      institution from January 2000 until December 2008 and compared outcomes, weight
      change, and Interagency Registry for Mechanically Assisted Circulatory Support
      defined adverse events between obese and nonobese patients. RESULTS: A total of
      169 patients were included; 113 (67%) nonobese and 56 (33%) obese. Baseline
      characteristics, pump types, and implant duration were similar for both
      populations with the exception of more diabetes (61% vs 26%, p < 0.0001) and
      hypertension (61% vs 42%, p = 0.019) in the obese. Outcomes on mechanical support
      at 6 months were not different between groups. There was no significant
      difference between the nonobese and obese groups in the change in body mass index
      (-0.3 vs -1.0 mg/m(2), p = 0.29) over the duration of support. Obese patients, as
      compared with the nonobese, had higher incidence rates of sepsis (64.5% vs 34.7%,
      respectively, p = 0.006) and reoperation for infectious complications (34.2% vs
      13.3%, respectively, p = 0.014). Obese patients also had a higher cumulative
      incidence of sepsis and reoperation for infection. Two-year posttransplant
      outcomes were not different in the obese and nonobese. CONCLUSIONS: Obese
      patients have similar outcomes on mechanical support, but at the cost of a higher
      cumulative incidence of sepsis and reoperations for infection; however, obese
      patients lose little weight while on mechanical support.

PMID- 21958792
TI  - Invited commentary.

PMID- 21958793
TI  - Vascularized atrial tissue patch cardiomyoplasty with omentopexy improves cardiac
      performance after myocardial infarction.
AB  - BACKGROUND: The tissue-engineered cardiac patch can alleviate ventricular
      remodeling and improve functional recovery in experimental myocardial infarction.
      However, the size of the engineered patch is limited due to insufficient
      vascularization. This study evaluated the effects of autologous atrial tissue
      patch cardiomyoplasty and omentopexy in rats with myocardial infarction. METHODS:
      Myocardial infarction was induced by left coronary artery ligation in Sprague
      Dawley rats. Three weeks later, either a patch of left atrium (A group) or
      omentum (O group) or both (OA group) were placed over the infarct zone. The
      atrial tissue patch was harvested from the autologous left atrial appendage along
      its long axis. The rats in the Control group received rethoracotomy only. After 4
      weeks, the survival of the transplanted atrial tissue patch, ventricular
      remodeling, and cardiac performance were examined. RESULTS: After 4 weeks,
      surviving myocardium was only detected in the OA group, as indicated by
      immunolabeling of cardiac troponin-I. Compared with the Control group, only
      animals in the OA group showed improved heart function assessed by left
      ventricular ejection fraction (57.9% +/- 5.8% vs 47.5% +/- 4.5%, p < 0.05) and
      left ventricular fractional shortening (25.2% +/- 3.6% vs 20.7% +/- 2.0%, p <
      0.05). The histologic analysis demonstrated increased scar thickness in the OA
      group. This was accompanied by increased angiogenesis of the border zone but
      decreased expression and activity of matrix metalloproteinase and endothelin-1
      levels. CONCLUSIONS: The omentopexy supported the survival of the autologous
      atrial tissue patch, which resulted in attenuated ventricular remodeling and
      restoration of heart function in rats with myocardial infarction. Our findings
      might represent a novel therapeutic strategy for heart failure.

PMID- 21958794
TI  - Invited commentary.

PMID- 21958795
TI  - Adhesive-enhanced sternal closure to improve postoperative functional recovery: a
      pilot, randomized controlled trial.
AB  - BACKGROUND: We previously established a proof-of-concept in a human cadaveric
      model where conventional wire cerclage was augmented with a novel biocompatible
      bone adhesive that increased mechanical strength and early bone stability. We
      report the results of a single-center, pilot, randomized clinical trial of the
      effects of adhesive-enhanced closure of the sternum on functional postoperative
      recovery. METHODS: In 55 patients undergoing primary sternotomy, 26 patients
      underwent conventional wire closure and were compared with 29 patients who
      underwent adhesive-enhanced closure, which consisted of Kryptonite biocompatible
      adhesive (Doctors Research Group Inc, Southbury, CT) applied to each sternal edge
      in addition to conventional 7-wire cerclage. Patients were monitored
      postoperatively at 72 hours, weekly for 12 weeks, and then after 12 months for
      incisional pain, analgesic use, and maximal inspiratory capacity measured by
      spirometry. Standardized assessment tools measured postoperative physical
      disability and health-related quality of life. RESULTS: No adverse events or
      sternal complications from the adhesive were observed early or after 12 months.
      Incisional pain and narcotic analgesic use were reduced in adhesive-enhanced
      closure patients. Inspiratory capacity was significantly improved, postoperative
      health-related quality of life scores normalized more rapidly, and physical
      disability scores were reduced. Computed tomography imaging was suggestive of
      sternal healing. CONCLUSIONS: Adhesive-enhanced closure is a safe and simple
      addition to conventional wire closure, with demonstrated benefits on functional
      recovery, respiratory capacity, incisional pain, and analgesic requirements. A
      large, multicenter, randomized controlled trial to examine the potential of the
      adhesive to prevent major sternal complications in higher risk patients is
      warranted.

PMID- 21958796
TI  - Invited commentary.

PMID- 21958797
TI  - Impact of the evolution of the Fontan operation on early and late mortality: a
      single-center experience of 405 patients over 3 decades.
AB  - BACKGROUND: Postoperative mortality has decreased in patients undergoing the
      Fontan operation, and the determinants of such mortality may also have changed
      significantly. METHODS: We conducted a study intended to focus on clarifying the
      determinants of mortality in 405 consecutive patients who had undergone a Fontan
      operation (62 patients after an atriopulmonary connection, 105 after an intra
      atrial rerouting, and 238 patients after an extracardiac rerouting) between 1979
      and 2010. RESULTS: The overall 1-year, 5-year, 10-year, and 15-year rates of
      survival were 87.1%, 84.6%, 83.4%, and 81.6%, respectively, and the type of
      procedure as well as heterotaxy syndrome, ventricular ejection fraction, and
      atrioventricular valve repair at the time of the Fontan operation were
      independent predictors of overall mortality (p < 0.05 for all). Heterotaxy
      syndrome and atrioventricular (AV) valve repair were independent predictors of
      early (less than 6 months postoperative) mortality and the type of procedure was
      an independent predictor of late (6 or more months postoperative) mortality (p <
      0.05 to 0.01). In the era of intra-atrial rerouting, heterotaxy syndrome was the
      only independent predictor of total, early, and late mortality (p < 0.05 for
      all), whereas a low ejection fraction, AV valve repair, and repair of a total
      anomalous pulmonary vein connection, rather than heterotaxy syndrome, were
      independent predictors of total or early mortality or both (p < 0.05 for all) in
      the era of extracardiac rerouting. CONCLUSIONS: Even in the modern era of
      extracardiac rerouting in the Fontan operation, a low ventricular ejection
      fraction, AV valve dysfunction, or a total anomalous pulmonary vein connection
      remain significant risk factors for mortality in patients with a single-ventricle
      physiology.

PMID- 21958798
TI  - Invited commentary.

PMID- 21958799
TI  - Side-to-side aorto-GoreTex central shunt warrants central shunt patency and
      pulmonary arteries growth.
AB  - BACKGROUND: Central shunts may be associated with a high rate of thrombosis and
      pulmonary artery distortion. METHODS: Between January 2000 and April 2010, 68
      consecutive patients underwent side-to-side aorto-Gore-Tex central shunts (W.L.
      Gore & Associates, Flagstaff, AZ). Median age at surgery was 31 days (8 to 122).
      Cardiac morphologies were tetralogy of Fallot (33), pulmonary atresia with
      collateral dependent lung circulation (20), and other (15). Shunt sizes ranged
      from 3 to 6 mm. The procedure was performed on cardiopulmonary bypass in 43
      patients (63%). RESULTS: Six patients died during hospital stay (9%) of low
      output syndrome (3), sepsis (2), and stroke (1). Only one shunt needed early
      redo. Follow-up was 100% complete. After a median follow-up of 236 days (116 to
      340), there were 7 late deaths related to sudden death (3), sepsis (2),
      reoperation (1), and lack of growth of pulmonary arteries with a patent shunt
      (1). Repair was completed in 42 patients and still pending in 12. Only one
      patient needed a late redo shunt (221 days). A larger shunt was performed in 5
      patients after a median of 139 days (130 to 258). In the 45 patients who had
      serial assessment of pulmonary arteries sizes, Nakata index increased from 83 +/-
      62 mm(2)/m(2) to 153 +/- 83 mm(2)/m(2) over a median period of 227 days (146 to
      330), with equal growth observed in both pulmonary arteries (p < 0.001).
      CONCLUSIONS: Central shunts can be performed in neonates and children with
      minimal risk of shunt occlusion. Side-to-side aorto-Gore-Tex anastomosis seems to
      reliably warrant shunt patency and harmonious growth of pulmonary arteries.

PMID- 21958800
TI  - Automated remote transapical wound closure system study.
AB  - PURPOSE: A readily applied and reliable means to create and close transapical
      wound access sites through a small intercostal opening could benefit many cardiac
      patients. Using relevant surgical tissue models, this research evaluated a new
      approach to enable single-port transapical wound site closure toward the eventual
      development of safe percutaneous access to the left ventricle. DESCRIPTION: Novel
      techniques and technologies were developed and successfully tested for remote
      automated placement of 2 pledgeted horizontal mattress sutures delivered
      concentrically around a transmural apical guidewire, which provided a tract to
      enable therapeutic intervention. Mechanical pledgeted knots secured these sutures
      after cannula removal. EVALUATION: Automated transapical closures were created in
      47 ex vivo porcine hearts and in 10 human cadavers, 8 through a thoracotomy and 2
      thoracoscopically. Automated apical closures achieved hemostasis in an acute
      beating heart thoracotomy model in 3 anesthetized pigs. An ex vivo porcine heart
      pressurized infusate model demonstrated the intraventricular pressure tolerated
      by automated closures (mean, 327 mm Hg) compared with hand-sutured closures
      (mean, 303 mm Hg). CONCLUSIONS: All automated apical closures were effective.
      Early results encourage further evaluation.

PMID- 21958801
TI  - Successful thoracoscopic resection of a large mediastinal liposarcoma.
AB  - We report a case of a rare, large mediastinal liposarcoma diagnosed in a 74-year
      old woman after a syncopal episode. Chest roentgenogram and computed tomographic
      scan showed a large mass occupying most of the right chest and abutting the great
      vessels and pericardium. A thoracoscopic approach was used for exploration and
      surgical excision of this large mediastinal mass. Despite the large size of the
      mass, the thoracoscopic approach offered excellent visualization of all the mass
      attachments and required only a small extension of the access incision for tumor
      removal. The mass was a well-differentiated liposarcoma, which was completely
      resected with clear margins. The patient remains disease-free almost 3 years
      after the resection.

PMID- 21958802
TI  - Transventricular mitral valve operations.
AB  - We report transventricular mitral valve operations in 2 patients with severe
      mitral regurgitation and postinfarction left ventricular rupture and
      pseudoaneurysm. The first patient had direct papillary muscle involvement
      necessitating replacement of the mitral valve. The second patient had indirect
      mitral involvement allowing for placement of an atrial mitral annuloplasty ring
      via the left ventricle. Both patients showed no mitral valve regurgitation after
      replacement or repair and had uneventful postoperative recoveries. These cases
      demonstrate a feasible, alternative, transventricular approach to mitral valve
      replacement and repair.

PMID- 21958803
TI  - Staged surgical repair for extensive cardiovascular damage by syphilis.
AB  - A 45-year-old man had aortic regurgitation with a syphilitic true aneurysm of the
      ascending to transverse arch aorta and a descending aortic aneurysm from chronic
      Stanford type B aortic dissection. After antibiotic therapy, two-staged surgical
      repair was performed and there has been no evidence of recurrence in 12 months
      since the second stage. We describe the successful management of extensive
      cardiovascular syphilitic damage.

PMID- 21958804
TI  - Immunoglobulin G4-related periaortitis mimicking an intramural hematoma.
AB  - Immunoglobulin G4 (IgG4)-related sclerosing disease in the cardiovascular system
      is a recently proposed disease entity, which is still unfamiliar to most
      clinicians. We present a case of IgG4-related periaortitis of the ascending aorta
      mimicking an intramural hematoma in the computed tomography (CT) scan, which led
      to an unnecessary surgery. IgG4-related periaortitis needs to be considered in
      the differential diagnosis in a patient with thickened aortic wall because the
      disease should be treated medically in light of its good response to steroid
      therapy.

PMID- 21958805
TI  - Intermittent coronary artery occlusion caused by a floating thrombus in the left
      coronary sinus of valsalva of a patient with a normal aorta and protein C
      deficiency.
AB  - A floating thrombus in the ascending aorta is an uncommon source of embolism. We
      report a case in which a floating mass in the left coronary sinus of Valsalva
      caused intermittent left main coronary trunk occlusion, leading to myocardial
      ischemia and cardiogenic shock. The mass was surgically resected.
      Macroscopically, the aortic wall and leaflets were normal. On histologic
      examination the mass was found to be a thrombus. This patient had a low level of
      protein C; therefore, it was presumed that the thrombus was due to protein C
      deficiency.

PMID- 21958806
TI  - Repair of lacerated intrapericardial inferior vena cava after cardiac massage.
AB  - We successfully undertook surgical treatment of intrapericardial laceration of
      the inferior vena cava caused by external cardiac massage in a patient with acute
      coronary syndrome. Injury to the inferior vena cava without blunt trauma is very
      rare, and diagnostic imaging does not show it clearly, making it difficult to
      diagnose. Rapid and accurate judgment and management are necessary, because the
      mortality due to this injury is very high.

PMID- 21958807
TI  - Delayed aortic rupture after aortic endograft placement in patient with spinal
      hardware.
AB  - Aortic injuries presenting in a delayed fashion after attempted repair of an
      acute injury are uncommon. We report a case of a patient presenting with an
      initial aortic injury associated with thoracic spinal hardware placement, which
      was repaired with an open and endovascular approach, and 5 months later presented
      with hemoptysis. The cause of hemoptysis was erosion of the descending thoracic
      aorta between the spinal hardware and the thoracic endograft. The patient
      underwent descending aorta replacement with a Dacron tube graft, removal of the
      hardware, and coverage with a pedicled omental flap. This is a unique
      presentation of erosion of the aorta between the spinal hardware and the earlier
      placed endovascular stent-graft.

PMID- 21958808
TI  - Off-pump plication of left ventricular aneurysm.
AB  - With a small left ventricular aneurysm, the surgeon finds it difficult to decide
      whether to repair the aneurysm or leave it alone; there are risks and benefits to
      consider. Our choice is plication rather than resection. The procedure may be
      performed on-pump or off-pump, and the results are easy to demonstrate with the
      help of transesophageal echocardiogram.

PMID- 21958809
TI  - Role of intragastric balloon in cardiac surgery: an adjunct to preoperative
      optimization for morbid obesity.
AB  - Obesity is associated with a high risk of developing intraoperative and
      postoperative complications in patients undergoing cardiac surgery. Morbid
      obesity is a relatively common cause for delay in surgery, whereas the patients
      are optimized to a near normal body mass index. We evaluate the role of
      intragastric balloon in this group of patients. We present the case of a 68-year
      old man who had successful treatment of his obesity prior to undergoing a
      successful triple bypass using an intragastric balloon. We draw the conclusion
      that intragastric balloon is a simple, safe procedure for preoperative
      optimization in patients with morbid obesity prior to cardiac surgery.

PMID- 21958810
TI  - Open aortic stent grafting and prosthetic bypass in a child.
AB  - Pseudoaneurysm is a major complication of percutaneous balloon angioplasty to
      treat recoarctation and restenosis after an interrupted aortic arch repair.
      Endovascular stent grafting to manage this complication has rarely been performed
      in children. We used a combination of open stent grafting and a prosthetic
      ascending aorta-to-descending aorta bypass to treat a pseudoaneurysm and
      ascending aorta stenosis in a 7-year-old child.

PMID- 21958812
TI  - Atrial septal dissection late after congenital heart surgery.
AB  - Atrial septal dissection is a rare entity usually seen after surgical mitral
      valve repair, myocardial infarction, or endocarditis. This is a report of an
      atrial dissection in a young girl found on routine follow-up echocardiography
      after repair of atrial and ventricular septal defects. No identifiable
      predisposing risk was found prior to or at the time of surgical repair.
      Considerable risk of significant morbidity and even mortality attends atrial
      dissection due to the risk of rupture.

PMID- 21958811
TI  - Traumatic aortic dissection in a boy with Loeys-Dietz syndrome.
AB  - A 9-year-old boy was admitted to the emergency department for interscapular chest
      discomfort. Bidimensional echocardiography revealed a severe aortic root and sino
      tubular junction dilatation with a suspicion of intimal flap at the aortic
      isthmus and a pseudo-aneurysm which was confirmed by a computerized tomography
      scan. The patient was immediately transferred to the operating room for an
      emergent replacement of the aortic isthmus. His recovery after surgery was
      uneventful, and he was discharged home 12 days later on beta blockers and
      angiotensin II receptor antagonist. A genetic recognition confirmed the diagnosis
      of Loeys-Dietz syndrome type I.

PMID- 21958813
TI  - Congenital aortopulmonary artery fistulas combined with bilateral coronary artery
      fistulas.
AB  - We describe an extremely rare case of "congenital aorto-pulmonary artery
      fistulas" combined with bilateral coronary artery fistulas associated with
      clinically significant left-to-right shunt. A multi-detector row computed
      tomographic scan revealed that tortuous anomalous vessels arising from the aortic
      arch, left anterior descending coronary artery, diagonal branch, and right
      coronary artery were connected to the main pulmonary trunk. After surgical
      intervention, the systemic-to-pulmonary flow ratio nearly normalized from 2.02 to
      1.05. We describe the case and speculate as to the embryological pathogenesis of
      these unique fistulas.

PMID- 21958814
TI  - Diaphragmatic defect complicating peritoneal dialysis.

PMID- 21958815
TI  - Meandering inferior vena cava in a child with pseudo-scimitar syndrome.

PMID- 21958816
TI  - Coincidental alignment of extracorporeal oxygenator cannula and central venous
      catheter.

PMID- 21958817
TI  - A new technique for dissection of the pulmonary vessels.
AB  - The conventional method for dissection of the pulmonary artery and vein has been
      described repeatedly [1-4]. However these sources have only presented dissection
      of the sheaths of vessels by exfoliation [1-3]. This article describes a new
      technique for the safe and rapid dissection of these vessels.

PMID- 21958818
TI  - Posterior chordal cutting in rheumatic mitral regurgitation due to hypomobility
      of the posterior leaflet.
AB  - A technique is described for correction of mitral regurgitation when the
      posterior leaflet has a reasonable length (approximately 10 mm), but its
      movements are limited by thickened and short chords. To avoid further retraction
      when a band or a ring is positioned to force leaflets coaptation, native chords
      are replaced by artificial chords (leaving 10 mm of extra length), which are then
      cut. In 6 patients, after 6 months of follow-up, the results are good.

PMID- 21958819
TI  - Free arterial graft with domino patch for coronary revascularization.
AB  - To improve the outcomes of coronary revascularization with free arterial grafts,
      we have devised a composite method that uses free arterial grafts with an
      arterial wall patch. After an arterial graft is anastomosed to the left external
      iliac artery (EIA), the EIA wall is excised (like a collar) and anastomosed to
      the aorta. The defect on the EIA is repaired with a vascular graft patch. Our
      domino patch method is simple, and it causes minimal wall thickness mismatch and
      allows the use of various arterial grafts anastomosed to any coronary artery. The
      procedures and early results are reported.

PMID- 21958820
TI  - Rapid pacing for the off-pump insertion of the Jarvik left ventricular assist
      device.
AB  - We present our technique for the implantation of the Jarvik 2000 left ventricular
      assist device (Jarvik Heart, Inc, New York, NY) without cardiopulmonary bypass by
      the induction of rapid pacing that allows the insertion of the apical device into
      the left ventricle, minimizing blood loss and surgical complications. Although
      the off-pump implantation of left ventricular assist devices is not new, our
      experience of rapid pacing has not been previously reported to our knowledge.

PMID- 21958821
TI  - Application of model score of prolonged air leak in the French database.

PMID- 21958822
TI  - Graft contraction phenomenon and tracheal stretching after tracheal replacement.

PMID- 21958824
TI  - Reexpansion pulmonary edema after large-volume thoracentesis.

PMID- 21958825
TI  - What is the optimal staging strategy for mediastinal lymph nodes in lung cancer?

PMID- 21958828
TI  - The surgical treatment of acute pulmonary embolism.

PMID- 21958830
TI  - The "important but forgotten role" of surgical treatment in the management of
      ventricular arrhythmias.

PMID- 21958832
TI  - Successful therapy of brachiocephalic arteriogastric fistula after esophagectomy.
AB  - We report the case of an 86-year-old man, who had undergone subtotal
      esophagectomy and reconstruction with a gastric tube through the retrosternal
      route 7 years ago, who was referred for treatment of a brachiocephalic
      arteriogastric fistula. An emergency stent-graft placement was performed to
      prevent massive bleeding from the fistula. After 2 weeks, a follow-up
      esophagogastroscopy revealed that the gastric tube ulcer had been penetrated, and
      the stent graft was exposed. Therefore, surgical treatment was indicated. After a
      carotid-carotid arterial bypass graft was made, the brachiocephalic artery was
      resected with the stent graft and the gastric wall. The defect between the
      cervical esophagus and the remnant gastric tube was replaced by a free jejunal
      graft. The patient tolerated these procedures well and was transferred to the
      referral hospital 3 months after surgery. Therefore, both an early diagnosis and
      the administration of multidisciplinary treatment are essential to save patients
      presenting with an arterioenteric fistula.

PMID- 21958833
TI  - Needle-tract seeding after percutaneous cryoablation for lung metastasis of
      colorectal cancer.
AB  - We report two cases of needle-tract seeding after percutaneous cryoablation for
      lung metastases of colorectal cancer. The targeted lung tumor was solitary in
      both cases. In patient 1, cryoablation was performed with a single cryoprobe,
      which was removed without freezing the cryoprobe tract. In patient 2,
      cryoablation was performed with two cryoprobes, both of which were removed after
      freezing of the cryoprobe tract. The seeding nodule appeared 5 and 7 months after
      cryoablation on the follow-up computed tomographic scan, respectively. In both
      cases, the seeding nodules were solitary and existed primarily in the
      subcutaneous to chest muscle layer, and could be completely resected under local
      anesthesia. Both lesions were pathologically confirmed as metastases from
      colorectal cancer. Local control was maintained in patient 1 for 4 years, until
      death due to progressive lung metastases. Patient 2 is alive without recurrences
      8 months after resection.

PMID- 21958834
TI  - Diffuse persistent interstitial pulmonary emphysema treated by lobectomy.
AB  - Persistent interstitial pulmonary emphysema is a rare condition that occurs in
      preterm infants on mechanical ventilation, characterized by abnormal accumulation
      of air in the pulmonary interstitium, due to disruption of the basement membrane.
      Diffuse persistent interstitial pulmonary emphysema is observed when small cysts
      are noted in all lobes of the lung. The management of infants suffering from
      diffuse persistent interstitial pulmonary emphysema varies according to severity
      and stability of the patient, being either conservative treatment or aggressive
      surgical treatment by pneumonectomy. We report a case of an unstable patient with
      diffuse persistent interstitial pulmonary emphysema successfully treated by
      lobectomy as a form of conservative surgical approach.

PMID- 21958836
TI  - Cyanosis after Kawashima-Fontan: hybrid approach to mixing and matching flows.
AB  - Surgical approaches to a single ventricle with absent infrahepatic segment of the
      inferior vena cava include a bidirectional Glenn and separate hepatic venous
      connection to the pulmonary arteries. If sites of insertion into the pulmonary
      arteries are widely separated, hepatic flow is directed to only one lung.
      Pulmonary arteriovenous malformations may form in the contralateral lung and
      result in severe cyanosis. We report a case of resolution of pulmonary
      arteriovenous malformations after successful rerouting of hepatic venous flow to
      the hemi-azygous vein in a 16-year-old patient. A dilatable pulmonary artery band
      reduced cyanosis by limiting flow to the affected lung until resolution of
      pulmonary arteriovenous malformations.

PMID- 21958835
TI  - Brucellosis relapse causing prosthetic valve endocarditis and aortic root
      infective pseudoaneurysm.
AB  - We report a previously treated case of brucellosis and aortic root replacement,
      which became complicated by prosthetic valve endocarditis and a massive aortic
      root pseudoaneurysm. Preoperative blood and intraoperative pseudoaneurysm wall
      cultures were positive for Brucella, and the patient was managed successfully
      with a combination of surgical and medical treatment. Brucella endocarditis is
      further discussed.

PMID- 21958837
TI  - Mediastinal calcified hydatid cyst.

PMID- 21958838
TI  - Thrombosed ventricular septal defect associated with a left ventricle aneurysm.

PMID- 21958839
TI  - Modified edge-to-edge technique for correction of congenital mitral regurgitation
      in infants and children.
AB  - Since 2008, 28 patients with congenital mitral regurgitation have undergone
      mitral valve repair with a modified edge-to-edge technique at our institution.
      The regurgitant mitral leaflet was sutured with a pledget-reinforced, horizontal
      mattress suture with No. 4-0 polypropylene on the ventricle side and a pledget
      reinforced mattress suture with Gore-Tex sutures (W.L. Gore & Associates,
      Flagstaff, AZ) and Dacron pledgets (Chest, Shanghai) placed on the anterior and
      posterior annulus corresponding to the edge-to-edge suturing site. Early results
      are encouraging, but a longer follow-up is needed.

PMID- 21958840
TI  - [Neurotrophic ulceration following thermocoagulation of the Gasserian ganglion].
AB  - INTRODUCTION: Neurotrophic ulceration (NTU) in the trigeminal nerve sensitive
      area is rare. It may be caused by a lesion anywhere on the trigeminal nerve's
      trajectory. The diagnosis is usually clinical, but other diagnoses, particularly
      neoplastic, must be ruled out first. The physiopathology and treatment of NTU
      remain controversial. We report a severe case of NTU and describe the main
      features of this poorly documented disease. OBSERVATION: A 67-year-old female
      patient consulted in the dermatology department for a progressive ulceration of
      the nose ala and the right upper lip, having developed over the two previous
      years. She had undergone two thermocoagulations of the right Gasserian ganglion
      for facial neuralgia 3 years before. The diagnosis of NTU, initially ruled out
      because of biopsies suggesting verrucous carcinoma, was finally retained because
      of the clinical presentation and anamnesis. Treatment consisted in surgical
      excision and primary reconstruction using a forehead flap. The diagnosis was
      confirmed after histopathological examination of the surgical specimen. A
      recurrence was noted 2 years postoperatively, then the patient was lost to follow
      up. DISCUSSION: The physiopathology of NTUs is badly documented. The cutaneous
      ulcerations look like facial neoplasms but the clinical findings (unilateral and
      paranasal location; lesion of the trigeminal nerve; local trauma; psychological
      instability) suggest neurotrophic ulceration. The histopathological examination,
      sometimes difficult, reveals non-specific chronic inflammatory ulceration. There
      is no consensus on treatment. The psychological profile may be a risk factor for
      recurrences and must be taken into account.

PMID- 21958841
TI  - Screening for tuberculosis among homeless shelter staff.
AB  - The prevalence of tuberculosis (TB) among homeless shelter staff was assessed
      using the tuberculin skin test (TST) and the Quantiferon TB-Gold in tube
      interferon-gamma release assay (QFT-TB). Investigation of 51 participants for
      whom both QFT-TB and TST results were available showed 47.1% and 43.1%
      positivity, respectively, with excellent (92%) concordance between the 2 tests.
      The high risk for acquiring occupational TB necessitates the development of TB
      surveillance protocols for homeless shelter staff in Italy.

PMID- 21958842
TI  - Separation of newly formed bone from older compact bone reveals clear
      compositional differences in bone matrix.
AB  - In long bone diaphyses, woven bone forms first and then transitions into a more
      mineralized compact bone tissue. Prior evidence suggests that the non-collagenous
      protein composition of woven bone may be distinct from that of more mature bone
      tissue, particularly with respect to a diverse group of phosphorylated,
      extracellular matrix proteins. To critically test this hypothesis, we developed
      an in situ approach to isolate newly formed bone from more mature bone within the
      same long bone, and combine this anatomical approach with Western blotting to
      make relative comparisons of 7 phosphorylated matrix proteins important for bone
      physiology and biomineralization. Interestingly, 75 kDa bone sialoprotein (BSP),
      63 kDa osteopontin, and the 75 kDa form of bone acidic glycoprotein-75 (BAG-75)
      were enriched in primary bone as opposed to more mature cortical bone, while
      osteonectin, fetuin A, matrix extracellular phosphoglycoprotein (MEPE) and dentin
      matrix protein-1 (DMP-1) appeared to be equally distributed between these two
      bone tissue compartments. Analyses also revealed the presence of larger sized
      forms of osteopontin (and to a lesser degree BSP) mostly in newly formed bone,
      while larger forms of BAG-75 were mostly detected in more mature cortical bone.
      Smaller sized forms of DMP-1 and BAG-75 were detected in both newly formed and
      more mature bone tissue extracts, and they are likely the result of proteolytic
      processing in vivo. Intact DMP-1 (97 kDa) was only detected in unmineralized
      matrix extracts. These findings indicate that newly formed bone exhibits a non
      collagenous matrix protein composition distinct from that of more mature compact
      bone even within the same long bone, and suggest that the temporal fate of
      individual non-collagenous proteins is variable in growing bone.

PMID- 21958843
TI  - Mechanical property and tissue mineral density differences among severely
      suppressed bone turnover (SSBT) patients, osteoporotic patients, and normal
      subjects.
AB  - Pathogenesis of atypical fractures in patients on long term bisphosphonate
      therapy is poorly understood, and the type, the manner in which they occur and
      the fracture sites are quite different from the usual osteoporotic fractures. We
      hypothesized that the tissue-level mechanical properties and mean degree of
      mineralization of the iliac bone would differ among 1) patients with atypical
      fractures and severely suppressed bone turnover (SSBT) associated with long-term
      bisphosphonate therapy, 2) age-matched, treatment-naive osteoporotic patients
      with vertebral fracture, 3) age-matched normals and 4) young normals. Large
      differences in tissue-level mechanical properties and/or mineralization among
      these groups could help explain the underlying mechanism(s) for the occurrence of
      typical osteoporotic and the atypical femoral shaft fractures. Elastic modulus,
      contact hardness, plastic deformation resistance, and tissue mineral densities of
      cortical and trabecular bone regions of 55 iliac bone biopsies--12 SSBT patients
      (SSBT; aged 49-77), 11 age-matched untreated osteoporotic patients with vertebral
      fracture (Osteoporotic), 12 age-matched subjects without bone fracture (Age
      Matched Normal), and 20 younger subjects without bone fracture (Young Normal)-
      were measured using nanoindentation and quantitative backscattered electron
      microscopy. For cortical bone nanoindentation properties, only plastic
      deformation resistance was different among the groups (p<0.05), with greater
      resistance to plastic deformation in the SSBT group compared to all other groups.
      For trabecular bone, all nanoindentation properties and mineral density of the
      trabecular bone were different among the groups (p<0.05). The SSBT group had
      greater plastic deformation resistance and harder trabecular bone compared to the
      other three groups, stiffer bone compared to the Osteoporotic and Young Normal
      groups, and a trend of higher mineral density compared to the Age-Matched Normal
      and Osteoporotic groups. Lower heterogeneity of modulus and contact hardness for
      cortical bone of the SSBT and trabecular bone of the Osteoporotic fracture
      groups, respectively, compared to the non-fractured groups, may contribute to
      fracture susceptibility due to lowered ability to prevent crack propagation. We
      tentatively conclude that, in addition to extremely low bone formation rate,
      atypical fractures in SSBT and/or long-term bisphosphonate treatment may be
      associated with greater mean plastic deformation resistance properties and less
      heterogeneous elastic properties of the bone.

PMID- 21958844
TI  - In vivo loading increases mechanical properties of scaffold by affecting bone
      formation and bone resorption rates.
AB  - A successful bone tissue engineering strategy entails producing bone-scaffold
      constructs with adequate mechanical properties. Apart from the mechanical
      properties of the scaffold itself, the forming bone inside the scaffold also adds
      to the strength of the construct. In this study, we investigated the role of in
      vivo cyclic loading on mechanical properties of a bone scaffold. We implanted
      PLA/beta-TCP scaffolds in the distal femur of six rats, applied external cyclic
      loading on the right leg, and kept the left leg as a control. We monitored bone
      formation at 7 time points over 35 weeks using time-lapsed micro-computed
      tomography (CT) imaging. The images were then used to construct micro-finite
      element models of bone-scaffold constructs, with which we estimated the stiffness
      for each sample at all time points. We found that loading increased the stiffness
      by 60% at 35 weeks. The increase of stiffness was correlated to an increase in
      bone volume fraction of 18% in the loaded scaffold compared to control scaffold.
      These changes in volume fraction and related stiffness in the bone scaffold are
      regulated by two independent processes, bone formation and bone resorption. Using
      time-lapsed micro-CT imaging and a newly-developed longitudinal image
      registration technique, we observed that mechanical stimulation increases the
      bone formation rate during 4-10 weeks, and decreases the bone resorption rate
      during 9-18 weeks post-operatively. For the first time, we report that in vivo
      cyclic loading increases mechanical properties of the scaffold by increasing the
      bone formation rate and decreasing the bone resorption rate.

PMID- 21958845
TI  - Meox2Cre-mediated disruption of CSF-1 leads to osteopetrosis and osteocyte
      defects.
AB  - CSF-1, a key regulator of mononuclear phagocyte production, is highly expressed
      in the skeleton by osteoblasts/osteocytes and in a number of nonskeletal tissues
      such as uterus, kidney and brain. The spontaneous mutant op/op mouse has been the
      conventional model of CSF-1 deficiency and exhibits a pleiotropic phenotype
      characterized by osteopetrosis, and defects in hematopoiesis, fertility and
      neural function. Studies to further delineate the biologic effect of CSF-1 within
      various tissues have been hampered by the lack of suitable models. To address
      this issue, we generated CSF-1 floxed/floxed mice and demonstrate that Cre
      mediated recombination using Meox2Cre, a Cre line expressed in epiblast during
      early embryogenesis, results in mice with ubiquitous CSF-1 deficiency (CSF-1KO).
      Homozygous CSF-1KO mice lacked CSF-1 in all tissues and displayed, in part, a
      similar phenotype to op/op mice that included: failure of tooth eruption,
      osteopetrosis, reduced macrophage densities in reproductive and other organs and
      altered hematopoiesis with decreased marrow cellularity, circulating monocytes
      and B cell lymphopoiesis. In contrast to op/op mice, CSF-1KO mice showed elevated
      circulating and splenic T cells. A striking feature in CSF-1KO mice was defective
      osteocyte maturation, bone mineralization and osteocyte-lacunar system that was
      associated with reduced dentin matrix protein 1 (DMP1) expression in osteocytes.
      CSF-1KO mice also showed a dramatic reduction in osteomacs along the endosteal
      surface that may have contributed to the hematopoietic and cortical bone defects.
      Thus, our findings show that ubiquitous CSF-1 gene deletion using a Cre-based
      system recapitulates the expected osteopetrotic phenotype. Moreover, results
      point to a novel link between CSF-1 and osteocyte survival/function that is
      essential for maintaining bone mass and strength during skeletal development.

PMID- 21958846
TI  - Synthesis and evaluation of a C-6 alkylated pyrimidine derivative for the in vivo
      imaging of HSV1-TK gene expression.
AB  - INTRODUCTION: We report on the synthesis, radiolabeling, in vitro and in vivo
      characterization of N-Me-[(18)F]FHBT (6-(3-[(18)F]fluoro-2-(hydroxymethyl)propyl)
      1,5-dimethylpyrimidin-2,4(1H,3H)-dione), a C-6-substituted N-1-methylated
      pyrimidine derivative as a reporter probe for imaging herpes simplex virus type 1
      thymidine kinase (HSV1-TK) expression. METHODS: N-Me-[(18)F]FHBT was synthesized
      via a standard nucleophilic substitution reaction followed by acidic cleavage of
      the methoxytrityl protecting group. Cell uptake was studied in vitro with control
      HEK293 (human embryonic kidney cells) and HEK293 cells stably transfected with
      nonmutant HSV1-tk (HEK293TK+ cells). Positron emission tomography (PET) imaging
      and biodistribution studies of N-Me-[(18)F]FHBT or [(18)F]FHBG were performed in
      nude mice bearing xenografts of HEK293 control and TK+ cells. RESULTS: N-Me
      [(18)F]FHBT was obtained in a two-step reaction in an overall maximal
      radiochemical yield (decay-corrected) of 5% and a radiochemical purity >96%. The
      tracer uptake in HSV1-TK containing HEK293TK+ cells was 14.5 times (at 30 min)
      and 55.4 times (at 240 min) higher than in control HEK293 cells. In mice, N-Me
      [(18)F]FHBT and [(18)F]FHBG accumulated significantly and exhibited similar
      radioactivity levels in the HEK293TK+ xenografts; however, standardized uptake
      values ratios between HEK293TK+ and HEK293 control xenografts were higher for
      [(18)F]FHBG than for N-Me-[(18)F]FHBT. Both tracers showed high gall bladder and
      abdominal activity. CONCLUSION: The biological evaluations demonstrated the
      feasibility of using N-methylated C-6-substituted pyrimidine derivative N-Me
      [(18)F]FHBT as a PET radiotracer for monitoring HSV1-TK expression in vivo.

PMID- 21958847
TI  - SPECT imaging of peripheral amyloid in mice by targeting hyper-sulfated heparan
      sulfate proteoglycans with specific scFv antibodies.
AB  - INTRODUCTION: Amyloid deposits are associated with a broad spectrum of disorders
      including monoclonal gammopathies, chronic inflammation, and Alzheimer's disease.
      In all cases, the amyloid pathology contains, in addition to protein fibrils, a
      plethora of associated molecules, including high concentrations of heparan
      sulfate proteoglycans (HSPGs). METHODS: We have evaluated radioiodinated scFvs
      that bind HS for their ability to image amyloid deposits in vivo. scFv's with
      different binding characteristics were isolated by phage display using HS
      extracted from bovine kidney or mouse and human skeletal muscle
      glycosaminoglycans (GAGs). Following purification and radioiodination, the
      biodistribution of (125)I-scFv's was assessed in mice with inflammation
      associated AA amyloidosis or in amyloid-free mice by using SPECT imaging,
      biodistribution measurements and tissue autoradiography. RESULTS: Four different
      scFv's all showed binding in vivo to amyloid in the spleen, liver and kidney of
      diseased mice; however, three of the scFv's also bound to sites within these
      organs in disease free mice. One scFv specific for hypersulfated HSPGs
      preferentially bound amyloid and did not accumulate in healthy tissues.
      CONCLUSIONS: These data indicate that HS expressed in amyloid deposits has unique
      qualities that can be distinguished from HS in normal tissues. A scFv specific
      for rare hypersulfated HS was used to selectively image AA amyloid in mice with
      minimal retention in normal tissue.

PMID- 21958848
TI  - PET study using [11C]FTIMD with ultra-high specific activity to evaluate I2
      imidazoline receptors binding in rat brains.
AB  - INTRODUCTION: We recently developed a selective (11)C-labeled I(2)-imidazoline
      receptor (I(2)R) ligand, 2-(3-fluoro-4-[(11)C]tolyl)-4,5-dihydro-1H-imidazole
      ([(11)C]FTIMD). [(11)C]FTIMD showed specific binding to I(2)Rs in rat brains
      having a high density of I(2)R, as well as to I(2)Rs those in monkey brains, as
      illustrated by positron emission tomography (PET) and autoradiography. However,
      [(11)C]FTIMD also showed moderate non-specific binding in rat brains. In order to
      increase the specificity for I(2)R in rat brains, we synthesized [(11)C]FTIMD
      with ultra-high specific activity and evaluated its binding. METHODS:
      [(11)C]FTIMD with ultra-high specific activity was prepared by a palladium
      promoted cross-coupling reaction of the tributylstannyl precursor and
      [(11)C]methyl iodide, which was produced by iodination of [(11)C]methane using
      the single-pass method. Dynamic PET scans were conducted in rats, and the kinetic
      parameters were estimated. RESULTS: [(11)C]FTIMD with ultra-high specific
      activity was successfully synthesized with an appropriate level of radioactivity
      and ultra-high specific activity (4470 +/- 1660 GBq/MUmol at end of synthesis, n
      = 11) for injection. In the PET study, distribution volume (V(T)) values in all
      the brain regions investigated whether I(2)R expression was greatly reduced in
      BU224-pretreatead rats compared with control rats (29-45% decrease). Differences
      in V(T) values between control and BU224-pretreated rats using [(11)C]FTIMD with
      ultra-high specific activity were greater than those using [(11)C]FTIMD with
      normal specific activity (17-34% decrease) in all brain regions investigated.
      CONCLUSION: Quantitative PET using [(11)C]FTIMD with ultra-high specific activity
      can contribute to the detection of small changes in I(2)R expression in the
      brain.

PMID- 21958849
TI  - Preparation and preclinical evaluation of 177Lu-nimotuzumab targeting epidermal
      growth factor receptor overexpressing tumors.
AB  - OBJECTIVES: Nimotuzumab (h-R3) is a humanized monoclonal antibody (mAb) which
      recognizes the external domain of the epidermal growth factor receptor (EGFR)
      with high specificity. It was demonstrated that h-R3 has a unique clinical
      profile for immunotherapy of adult gliomas and pediatric pontine gliomas. The aim
      of this work was to evaluate the conjugate (177)Lu-h-R3 as a potential
      radioimmunoconjugate for radioimmunotherapy (RIT) of tumors overexpressing EGFR.
      METHODS: h-R3 was modified with the macrocylcic ligand S-2-(4
      isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid (p-SCN-Bn
      DOTA) and the acyclic ligand S-2-(4-Isothiocyanatobenzyl)-diethylenetriamine
      pentaacetic acid (p-SCN-Bn-DTPA); the immunoconjugates were labeled with no
      carried added (177)Lu. Specificity and affinity were tested using
      radioimmunoassays in a cell line overexpressing EGFR. Biodistribution in mice,
      healthy or bearing A431 epithelial carcinoma xenografts, was performed for 11
      days. Tumor uptake, the influence of the nature of the chelate and the way of
      administration were studied. Absorbed dose in tumor and selected organs was
      calculated using the OLINDA/EXM software; the data from the animals was
      extrapolated to humans. RESULTS: (177)Lu-h-R3 conjugates were obtained with
      specific activity up to 915 MBq/mg without significant loss of immunoreactivity.
      The binding of (177)Lu-h-R3 conjugates to A431 cells showed to be EGFR specific,
      and the affinity was similar to native h-R3. Tumor uptake reached a maximum value
      of 22.4+/-3.1 %ID/g at 72 h and remained ~20% ID/g over 1 week. Locoregional
      application showed better tumor/nontumor ratios than intravenous application.
      CONCLUSIONS: (177)Lu-h-R3 should be considered for further evaluations as a
      potential radiopharmaceutical for RIT of tumors overexpressing EGFR.

PMID- 21958850
TI  - Synthesis of [11C]interleukin 8 using a cell-free translation system and L
      [11C]methionine.
AB  - Positron emission tomography (PET), which requires a compound labeled with a
      positron emitter radioisotope as an imaging probe, is one of the most useful and
      valuable imaging modalities in molecular imaging. It has several advantages over
      other imaging modalities, particularly in sensitive and quantitative
      investigations of molecular functions and processes in vivo. Recent advances in
      biopharmaceuticals development have increased interest in practical methods for
      proteins and peptides labeling with positron emitter radioisotope for PET
      molecular imaging. Here, we propose a novel approach for preparing positron
      emitter-labeled proteins and peptides based on biochemical synthesis using a
      reconstituted cell-free translation system. In this study, [(11)C]interleukin 8
      (IL-8; MW 9.2 kDa) was successfully synthesized by the cell-free system in
      combination with l-[(11)C]methionine. The in vitro biochemical reaction proceeded
      smoothly and gave maximum radioactivity of [(11)C]IL-8 at 20 min with a
      radiochemical yield of 63%. Purification of [(11)C]IL-8 was achieved by
      conventional cation exchange and ultrafiltration methods, resulting in enough
      amount of radioactivity with excellent radiochemical purity (>95%) for small
      animal imaging. This study clearly demonstrates that cell-free protein production
      system combined with positron emitter-labeled amino acid holds great promise as a
      novel approach to prepare radiolabeled proteins and peptides for PET imaging.

PMID- 21958851
TI  - Usefulness of [18F]-DA and [18F]-DOPA for PET imaging in a mouse model of
      pheochromocytoma.
AB  - PURPOSE: To evaluate the usefulness of [(18)F]-6-fluorodopamine ([(18)F]-DA) and
      [(18)F]-L-6-fluoro-3,4-dihydroxyphenylalanine ([(18)F]-DOPA) positron emission
      tomography (PET) in the detection of subcutaneous (s.c.) and metastatic
      pheochromocytoma in mice; to assess the expression of the norepinephrine
      transporter (NET) and vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2),
      all important for [(18)F]-DA and [(18)F]-DOPA uptake. Furthermore, to compare
      tumor detection by micro-computed tomography (microCT) to magnetic resonance
      imaging (MRI) in individual mouse. METHODS: SUV(max) values were calculated from
      [(18)F]-DA and [(18)F]-DOPA PET, tumor-to-liver ratios (TLR) were obtained and
      expression of NET, VMAT1 and VMAT2 was evaluated. RESULTS: [(18)F]-DA detected
      less metastatic lesions compared to [(18)F]-DOPA. TLR values for liver metastases
      were 2.26-2.71 for [(18)F]-DOPA and 1.83-2.83 for [(18)F]-DA. A limited uptake of
      [(18)F]-DA was found in s.c. tumors (TLR = 0.22-0.27) compared to [(18)F]-DOPA
      (TLR = 1.56-2.24). Overall, NET and VMAT2 were expressed in all organ and s.c.
      tumors. However, s.c. tumors lacked expression of VMAT1. We confirmed [(18)F]
      DA's high affinity for the NET for its uptake and VMAT1 and VMAT2 for its storage
      and retention in pheochromocytoma cell vesicles. In contrast, [(18)F]-DOPA was
      found to utilize only VMAT2. CONCLUSION: MRI was superior in the detection of all
      organ tumors compared to microCT and PET. [(18)F]-DOPA had overall better
      sensitivity than [(18)F]-DA for the detection of metastases. Subcutaneous tumors
      were localized only with [(18)F]-DOPA, a finding that may reflect differences in
      expression of VMAT1 and VMAT2, perhaps similar to some patients with
      pheochromocytoma where [(18)F]-DOPA provides better visualization of lesions than
      [(18)F]-DA.

PMID- 21958853
TI  - Transport mechanisms of trans-1-amino-3-fluoro[1-(14)C]cyclobutanecarboxylic acid
      in prostate cancer cells.
AB  - INTRODUCTION: We investigated the mechanisms of trans-1-amino-3-fluoro[1
      (14)C]cyclobutanecarboxylic acid (anti-[(14)C]FACBC) transport by human-derived
      prostate cancer (PCa) cells and normal human prostatic epithelial cells (PrECs).
      METHODS: Using PCa cells (DU145, PC-3, LNCaP) and PrECs, we performed the
      following in vitro experiments: time-course, kinetics, competitive inhibition by
      synthetic/naturally occurring amino acids (AAs), exchange transport with
      synthetic/naturally occurring AAs and pH-dependency of anti-[(14)C]FACBC uptake.
      We also examined the amino acid transporter (AAT) expression using flow
      cytometry. RESULTS: The uptake of anti-[(14)C]FACBC by LNCaP and DU145 cells was
      higher than that by PC-3 and PrECs. The K(m) values for anti-[(14)C]FACBC were
      64.4 and 191.7 MUmol/L in the DU145 cells and PrECs, respectively. Total levels
      of anti-[(14)C]FACBC uptake were positively correlated with the expression level
      of system ASC in PCa cells. The contributions of Na(+)-dependent AATs to anti
      [(14)C]FACBC uptake were greater than those of Na(+)-independent AATs, especially
      in PCa cells. In the presence of Na(+), glutamine and serine showed the strongest
      inhibitory effect against anti-[(14)C]FACBC uptake, suggesting that system ASC,
      especially ASCT2, is an important AAT for anti-[(14)C]FACBC. In contrast,
      phenylalanine and 2-amino-bicyclo[2,2,1]heptane-2-carboxylic acid, but not N
      ethylmaleimide, almost completely inhibited the anti-[(14)C]FACBC uptake in the
      absence of Na(+), indicating the contribution of LAT1. In the exchange transport
      experiments, glutamine showed the strongest transstimulation of intracellular
      anti-[(14)C]FACBC efflux in DU145 cells. Furthermore, the contributions of Na(+)
      independent AATs to the uptake of anti-[(14)C]FACBC in DU145 and PrECs were
      greater under acidic pH conditions than under neutral or alkaline pH conditions.
      CONCLUSIONS: Total uptake of anti-[(14)C]FACBC by PCa cells correlates with the
      expression level of system ASC in PCa cells. Furthermore, LAT1 is an important
      transport system for anti-[(14)C]FACBC uptake, especially in an acidic
      environment, such as the intra-tumoural environment.

PMID- 21958852
TI  - Radioimmunotargeting of malignant glioma by monoclonal antibody D2C7 reactive
      against both wild-type and variant III mutant epidermal growth factor receptors.
AB  - INTRODUCTION: Malignant glioma remains a significant therapeutic challenge, and
      immunotherapeutics might be a beneficial approach for these patients. A
      monoclonal antibody (MAb) specific for multiple molecular targets could expand
      the treatable patient population and the fraction of tumor cells targeted, with
      potentially increased efficacy. This motivated the generation of MAb D2C7, which
      recognizes both wild-type epidermal growth factor receptor (EGFRwt) and a tumor
      specific mutant, EGFRvIII. METHODS: D2C7 binding affinity was determined by
      surface plasmon resonance and its specificity characterized through comparison to
      EGFRwt-specific EGFR.1 and EGFRvIII-specific L8A4 MAbs by flow cytometry and
      immunohistochemical analysis. The three MAbs were labeled with (125)I or (131)I
      using Iodogen, and paired-label internalization assays and biodistribution
      experiments in athymic mice with human tumor xenografts were performed. RESULTS:
      The affinity of D2C7 for EGFRwt and EGFRvIII was 5.2*10(9) M(-1) and 3.6*10(9) M(
      1), and cell-surface reactivity with both receptors was documented by flow
      cytometry. Immunohistochemical analyses revealed D2C7 reactivity with malignant
      glioma tissue from 90 of 101 patients. Internalization assays performed on EGFRwt
      expressing WTT cells and EGFRvIII-expressing NR6M cells indicated a threefold
      lower degradation of (125)I-labeled D2C7 compared with (131)I-labeled EGFR.1.
      Uptake of (125)I-labeled D2C7 in NR6M xenografts (52.45+/-13.97 %ID g(-1) on Day
      3) was more than twice that of (131)I-labeled L8A4; a threefold to fivefold tumor
      delivery advantage was seen when compared to (131)I-labeled EGFR.1 in mice with
      WTT xenografts. CONCLUSIONS: These results suggest that D2C7 warrants further
      evaluation for the development of MAb-based therapeutics against cancers
      expressing EGFRwt and EGFRvIII.

PMID- 21958854
TI  - Comparing the intracellular fate of components within a noncovalent streptavidin
      nanoparticle with covalent conjugation.
AB  - INTRODUCTION: Auger radiotherapy requires adequate tumor delivery and high
      nuclear accumulation and retention. We hypothesize that the noncovalent nature of
      a streptavidin/biotin three-component nanoparticle possessing these qualities may
      be required for dissociation of the radiolabeled oligomer and its accumulation
      into the cell nucleus. METHODS: As a test of our hypothesis, the intracellular
      fate of an antisense oligomer when incubated as the nanoparticle and when
      incubated while covalently conjugated to the antibody was compared. The three
      component noncovalent nanoparticle consisted of streptavidin linking three
      biotinylated components: a Cy3-labeled anti-RIalpha antisense phosphorodiamidate
      morpholino (MORF) oligomer, a tat transfecting peptide and the anti-Her2
      herceptin antibody. The covalent constructs included an anti-RIalpha antisense
      DNA conjugated to a radiolabeled herceptin and a fluorescent DNA conjugated to
      native herceptin. Fluorescence microscopy in SK-BR-3 (Her2+) cells was used to
      evaluate the fate of the fluorescent Cy5.5-DNA and Cy3-MORF, while the
      subcellular accumulation of the (111)In-labeled herceptin and herceptin-DNA in
      both SK-BR-3 and MDA-MB-231 (Her2) cells was determined by isolating and counting
      the nuclear fractions. RESULTS: Previously, we demonstrated that when incubated
      as the three-component nanoparticle consisting of herceptin and streptavidin and
      (99m)Tc-labeled antisense MORF, only the MORF accumulated in the nucleus of Her2+
      cells. In this investigation, clear evidence was observed of nuclear accumulation
      of the antisense oligomer within the noncovalent nanoparticle as before, but when
      incubated as the covalent construct, by both fluorescence microscopy and nuclear
      counting, no evidence of nuclear accumulation was observed. CONCLUSION: The
      weaker noncovalent biotin-streptavidin bond may be essential for adequate
      delivery of the radiolabeled antisense oligomer to the nucleus of tumor cells.

PMID- 21958855
TI  - Radiotracer properties determined by high performance liquid chromatography: a
      potential tool for brain radiotracer discovery.
AB  - INTRODUCTION: Previously, development of novel brain radiotracers has largely
      relied on simple screening tools. Improved selection methods at the early stages
      of radiotracer discovery and an increased understanding of the relationships
      between in vitro physicochemical and in vivo radiotracer properties are needed.
      We investigated if high performance liquid chromatography (HPLC) methodologies
      could provide criteria for lead candidate selection by comparing HPLC
      measurements with radiotracer properties in humans. METHODS: Ten molecules,
      previously used as radiotracers in humans, were analysed to obtain the following
      measures: partition coefficient (Log P); permeability (P(m)); percentage of
      plasma protein binding (%PPB); and membrane partition coefficient (K(m)).
      Relationships between brain entry measurements (Log P, P(m) and %PPB) and in vivo
      brain percentage injected dose (%ID); and K(m) and specific binding in vivo
      (BP(ND)) were investigated. Log P values obtained using in silico packages and
      flask methods were compared with Log P values obtained using HPLC. RESULTS: The
      modelled associations with %ID were stronger for %PPB (r(2)=0.65) and P(m)
      (r(2)=0.77) than for Log P (r(2)=0.47) while 86% of BP(ND) variance was explained
      by K(m). Log P values were variable dependant on the methodology used.
      CONCLUSIONS: Log P should not be relied upon as a predictor of blood-brain
      barrier penetration during brain radiotracer discovery. HPLC measurements of
      permeability, %PPB and membrane interactions may be potentially useful in
      predicting in vivo performance and hence allow evaluation and ranking of compound
      libraries for the selection of lead radiotracer candidates at early stages of
      radiotracer discovery.

PMID- 21958856
TI  - Enhanced antiproliferative effects of combination hexokinase II shRNA and NIS
      gene therapy on vascular smooth muscle cells.
AB  - INTRODUCTION: This study was designed to determine the antiproliferative effects
      of combination gene therapy using sodium iodide symporter (NIS)-based radioiodine
      and lentivirus-mediated short hairpin RNA (shRNA) against hexokinase II (HKII) on
      vascular smooth muscle cells (VSMCs). METHODS: A7r5 rat VSMCs were stably
      transfected with a dual-expression vector of NIS and Fluc (A7r5-NL cells).
      Functional assessment was performed by radioiodine uptake assay, luciferase assay
      and confocal microscopy. After exposure to lentivirus-HKII-shRNA, the (18)F-FDG
      uptake test and HK activity assay were performed. The effects of combination
      therapy with (131)I and lentivirus-HKII-shRNA on VSMCs were assessed with an in
      vitro clonogenic assay. In vivo bioluminescence and nuclear imaging were
      undertaken using a xenografted mouse model. RESULTS: In vitro functional
      assessment confirmed expression of NIS and Fluc genes in A7r5-NL, but not in
      parent A7r5 cells. Transfection of lentivirus-HKII-shRNA resulted in a
      significant decrease in messenger RNA expression of the HKII gene, (18)F-FDG
      uptake and HK activity. The cell survival rate of A7r5-NL decreased to 61.9% and
      90.5% by single therapy with 7.4 MBq of (131)I or lentivirus-HKII-shRNA,
      respectively, and further decreased to 42.9% by combined therapy (P<.05). In vivo
      bioluminescent and gamma camera images clearly demonstrated optical signals and
      (99m)Tc pertechnetate uptake at the site of A7r5-NL cell inoculation in nude
      mice. CONCLUSION: The enhanced antiproliferative effect on VSMCs was achieved by
      a combination of NIS-based radioiodine and lentivirus-mediated HKII shRNA gene
      therapy. Successful demonstration of in vivo dual reporter gene imaging assures
      the potential for further application in an animal model.

PMID- 21958857
TI  - The influence of mass of [11C]-laniquidar and [11C]-N-desmethyl-loperamide on P
      glycoprotein blockage at the blood-brain barrier.
AB  - INTRODUCTION: An earlier report suggested that mass amount of PET tracers could
      be an important factor in brain uptake mediated by P-glycoprotein. Thereby, this
      study investigated the influence of mass dose of laniquidar, desmethyl-loperamide
      and loperamide on the P-glycoprotein-mediated brain uptake of, respectively,
      [(11)C]-laniquidar and [(11)C]-N-desmethyl-loperamide ([(11)C]-dLop). METHODS:
      Wild-type (WT) mice were injected intravenously with solutions of 5.6 MBq [(11)C]
      laniquidar (either no carrier added or 60 mg/kg laniquidar added) or with 5.0-7.4
      MBq [(11)C]-dLop (either no carrier added or 3 mg/kg desmethyl loperamide). Mice
      were killed, and brain and blood were collected, weighted and counted for
      radioactivity. Mdr1a(-/-) knockout mice were incorporated as the control group.
      RESULTS: Injection of (11)C-laniquidar (no carrier added) in WT mice resulted in
      a statistical significant lower brain uptake (0.7+/-0.2 %ID/g) compared to the
      carrier-added formulation (60 mg/kg laniquidar) (3.1+/-0.3 %ID/g) (P=.004), while
      no statistical difference could be observed between formulations of [(11)C]-dLop.
      The [(11)C]-laniquidar and [(11)C]-dLop blood concentrations were not
      significantly different between the tested formulations in WT mice. In control
      animals, no effect of mass amount on brain uptake of both tracers could be
      demonstrated. CONCLUSIONS: These results demonstrate the bivalent character of
      laniquidar, acting as a substrate at low doses and as a blocking agent for P
      glycoprotein transport in the brain at higher doses. In comparison, no difference
      was observed in [(11)C]-dLop uptake between carrier- and no-carrier-added
      formulations, which confirms that desmethyl-loperamide is a substrate of P
      glycoprotein at the blood-brain barrier.

PMID- 21958858
TI  - Pharmacokinetics, dosimetry and comparative efficacy of 188Re-liposome and 5-FU
      in a CT26-luc lung-metastatic mice model.
AB  - The biodistribution, pharmacokinetics, dosimetry and comparative therapeutic
      efficacy of intravenously administrated (188)Re-N,N-bis(2-mercaptoethyl)-N',N'
      diethylethylenediamine (BMEDA)-labeled pegylated liposome ((188)Re-liposome) and
      5-FU were investigated in a CT26-luc lung-metastatic model. After intravenous
      administration of (188)Re-liposome, tumor accumulation from the radioactivity was
      observed. Levels of radioactivity in tumors were maintained at steady levels
      (from 5.40 to 5.67 %ID/g) after 4 to 24 h. In pharmacokinetics, the AUC((0
      >infinity)), MRT((0->infinity)) and Cl of (188)Re-liposome in blood via
      intravenous route were 998 h %ID/ml, 28.7 h and 0.1 ml/h, respectively. The total
      excreted fractions of feces and urine were 0.61 and 0.26, respectively. Absorbed
      doses for (188)Re-liposome in the liver and red marrow were 0.31 and 0.08
      mSv/MBq, respectively. Tumor-absorbed doses for (188)Re-liposome ranged from 48.4
      to 1.73 mGy/MBq at 10 to 300 g tumor spheres. In therapeutic efficacy, the
      survival times of mice after (188)Re-liposome [80% maximum tolerated dose (MTD);
      29.6 MBq], 5-FU (80% MTD; 144 mg/kg), liposome or normal saline treatments were
      evaluated. Consequently, radiotherapeutics of (188)Re-liposome attained a longer
      lifespan (increase of 34.9%; P=.005) in mice than in the normal saline group. The
      increase in lifespan of the (188)Re-liposome group was 2.5-fold greater than that
      of the 5-FU group. Therefore, intravenous administration of (188)Re-liposome
      could provide a benefit and it is a promising strategy for delivery of passive
      nanotargeted radiotherapeutics in oncology applications.

PMID- 21958859
TI  - Comparison of therapeutic efficacy and biodistribution of 213Bi- and 211At
      labeled monoclonal antibody MX35 in an ovarian cancer model.
AB  - INTRODUCTION: The purpose of this study was to compare the therapeutic efficacy
      and biodistribution of the monoclonal antibody MX35 labeled with either (213)Bi
      or (211)At, both alpha-emitters, in an ovarian cancer model. METHODS: One hundred
      female nude BALB/c (nu/nu) mice were inoculated intraperitoneally with human
      ovarian cancer cells (OVCAR-3). Two weeks later, 40 of these mice were injected
      intraperitoneally with ~2.7 MBq of (213)Bi-MX35 (n=20) or ~0.44 MBq of (211)At
      MX35 (n=20). Four weeks after inoculation, 40 new OVCAR-3-inoculated mice were
      injected with the same activities of (213)Bi-MX35 (n=20) or (211)At-MX35 (n=20).
      Presence of tumors and ascites was investigated 8 weeks after therapy.
      Biodistributions of intraperitoneally injected (213)Bi-MX35 and (211)At-MX35 were
      studied in tumor-free nude BALB/c (nu/nu) mice (n=16). RESULTS: The animals
      injected with (213)Bi-MX35 or (211)At-MX35 2 weeks after cell inoculation had
      tumor-free fractions (TFFs) of 0.60 and 0.90, respectively. The untreated
      reference group had a TFF of 0.20. The groups treated with (213)Bi-MX35 or
      (211)At-MX35 4 weeks after inoculation both had TFFs of 0.25, and the reference
      animals all exhibited evidence of disease. The biodistributions of (213)Bi-MX35
      and (211)At-MX35 were very similar to each other and displayed no alarming
      activity levels in the investigated organs. CONCLUSIONS: Micrometastatic growth
      of an ovarian cancer cell line was reduced in nude mice after treatment with
      (213)Bi-MX35or (211)At-MX35. Treatment with (211)At-MX35 provided a non
      significantly better result for the chosen activity levels. The radiolabeled MX35
      did not accumulate to a high extent in the investigated organs. No considerable
      signs of toxicity were observed.

PMID- 21958860
TI  - Galanin differentially regulates acetylcholine release in ventral and dorsal
      hippocampus: a microdialysis study in awake rat.
AB  - The purpose of the present study was to investigate, by use of in vivo
      microdialysis technique, the regulatory role of galanin on acetylcholine (ACh)
      release in the CA1, CA3, and dentate gyrus (DG) subregions of rat dorsal and
      ventral hippocampus. In the ventral hippocampus, local infusions of galanin (1.5
      nmol) into CA1, and CA3, but not DG (3 nmol), decreased basal ACh release to
      58.6% and 68.4%, respectively. In addition, local infusion of galanin (1.5 nmol)
      into the ventral DG, and CA3 areas decreased basal ACh levels in the CA1 to 51.2%
      and 84%, respectively. This observation implies that the effects of galanin are
      unlikely to be mediated via galanin autoreceptors on the cholinergic terminals,
      but rather via mechanisms involving galanin internalization and modulation of
      hippocampo-septo-hippocampal loops, attenuation of the excitability of the
      principal cells, or indirect modulation by galanin-containing vasopressin
      terminals to the ventral and/or dorsal hippocampus. In the dorsal hippocampus,
      galanin infusion (1.5 nmol) into the CA1 region increased ACh release to 128.2%
      of the control levels, but infusions of galanin had no effects in the CA3 and DG.
      In all cases, the ACh levels returned to basal values within 100 min after the
      galanin infusion. It is concluded that the attenuating effects of galanin on ACh
      release in the ventral hippocampus and increase in ACh release in the dorsal
      hippocampus are in line and support the current view on molecular and functional
      distinction between the ventral hippocampus being involved preferentially in
      motivational and emotional behavior, whereas the dorsal hippocampus is primarily
      implicated in cognitive processes of learning and memory.

PMID- 21958861
TI  - Regulation of POU4F3 gene expression in hair cells by 5' DNA in mice.
AB  - The POU-domain transcription POU4F3 is expressed in the sensory cells of the
      inner ear. Expression begins shortly after commitment to the hair cell (HC) fate,
      and continues throughout life. It is required for terminal HC differentiation and
      survival. To explore regulation of the murine Pou4f3 gene, we linked enhanced
      green fluorescent protein (eGFP) to 8.5 kb of genomic sequence 5' to the start
      codon in transgenic mice. eGFP was uniformly present in all embryonic and
      neonatal HCs. Expression of eGFP was also observed in developing Merkel cells and
      olfactory neurons as well as adult inner and vestibular HCs, mimicking the normal
      expression pattern of POU4F3 protein, with the exception of adult outer HCs.
      Apparently ectopic expression was observed in developing inner ear neurons. On a
      Pou4f3 null background, the transgene produced expression in embryonic HCs which
      faded soon after birth both in vivo and in vitro. Pou4f3 null HCs treated with
      caspase 3 and 9 inhibitors survived longer than untreated HCs, but still showed
      reduced expression of eGFP. The results suggest the existence of separate
      enhancers for different HC types, as well as strong autoregulation of the Pou4f3
      gene. Bioinformatic analysis of four divergent mammalian species revealed three
      highly conserved regions within the transgene: 400 bp immediately 5' to the
      Pou4f3 ATG, a short sequence at -1.3 kb, and a longer region at -8.2 to -8.5 kb.
      The latter contained E-box motifs that bind basic helix-loop-helix (bHLH)
      transcription factors, including motifs activated by ATOH1. Cotransfection of
      HEK293 or VOT-E36 cells with ATOH1 and the transgene as a reporter enhanced eGFP
      expression when compared with the transgene alone. Chromatin immunoprecipitation
      of the three highly conserved regions revealed binding of ATOH1 to the distal
      most conserved region. The results are consistent with regulation of Pou4f3 in
      HCs by ATOH1 at a distal enhancer.

PMID- 21958862
TI  - Upregulated vimentin suggests new areas of neurodegeneration in a model of an
      alcohol use disorder.
AB  - Excessive alcohol intake, characteristic of an alcohol use disorder (AUD),
      results in neurodegeneration as well as cognitive deficits that may recover in
      abstinence. Neurodegeneration in psychiatric disorders such as AUDs is due to
      various effects on tissue integrity. Several groups report that alcohol-induced
      neurodegeneration and recovery include a role for adult neurogenesis. Therefore,
      the initial purpose of this study was to investigate the effect of alcohol on the
      temporal profile of neural progenitor cells using the radial glia marker,
      vimentin, in a model of an AUD. However, striking vimentin expression throughout
      corticolimbic regions led, instead, to the discovery of a significant gliosis
      response in this model. Adult male rats were subjected to a 4-day binge model of
      an AUD and brains harvested for immunohistochemistry at 0, 2, 4, 7, 14, and 28
      days following the last dose of ethanol. A prominent increase in vimentin
      immunoreactivity was apparent at 4 and 7 days post binge that returned to control
      levels by 14 days in the corticolimbic regions examined. Vimentin-positive cells
      co-labeled with glial fibrillary acidic protein (GFAP), which suggested that
      cells were reactive astrocytes. A second experiment supported that increased
      vimentin was not primarily due to alcohol withdrawal seizures and is more likely
      due to alcohol-induced cell death. As this gliosis was remarkably distinct in
      regions where cell death had not previously been reported in this model, adjacent
      tissue sections were processed for FluoroJade B staining for cell death.
      FluoroJade B-positive cells were evident immediately following the last ethanol
      dose as expected, but were significantly elevated in the hippocampal dentate
      gyrus and CA3 regions and corticolimbic regions from 2 to 7 days post binge.
      Intriguingly, vimentin labeling of astrogliosis is more widespread than
      FluoroJade B labeling of cell death, which suggests that 4-day binge ethanol
      consumption is more damaging than originally realized.

PMID- 21958863
TI  - 5-hydroxytryptamine 2C receptors in the dorsal striatum mediate stress-induced
      interference with negatively reinforced instrumental escape behavior.
AB  - Uncontrollable stress can interfere with instrumental learning and induce anxiety
      in humans and rodents. While evidence supports a role for serotonin (5-HT) and
      serotonin 2C receptors (5-HT(2C)R) in the behavioral consequences of
      uncontrollable stress, the specific sites of action are unknown. These
      experiments sought to delineate the role of 5-HT and 5-HT(2C)R in the dorsal
      striatum (DS) and the lateral/basolateral amygdala (BLA) in the expression of
      stress-induced instrumental escape deficits and exaggerated fear, as these
      structures are critical to instrumental learning and fear behaviors. Using in
      vivo microdialysis, we first demonstrated that prior uncontrollable, but not
      controllable, stress sensitizes extracellular 5-HT in the dorsal striatum, a
      result that parallels prior work in the BLA. Additionally, rats were implanted
      with bi-lateral cannula in either the DS or the BLA and exposed to uncontrollable
      tail shock stress. One day later, rats were injected with 5-HT(2C)R antagonist
      (SB242084) and fear and instrumental learning behaviors were assessed in a
      shuttle box. Separately, groups of non-stressed rats received an intra-DS or an
      intra-BLA injection of the 5-HT(2C)R agonist (CP809101) and behavior was
      observed. Intra-DS injections of the 5-HT(2C)R antagonist prior to fear/escape
      tests completely blocked the stress-induced interference with instrumental escape
      learning; a partial block was observed when injections were in the BLA.
      Antagonist administration in either region did not influence stress-induced fear
      behavior. In the absence of prior stress, intra-DS administration of the 5
      HT(2C)R agonist was sufficient to interfere with escape behavior without
      enhancing fear, while intra-BLA administration of the 5-HT(2C)R agonist increased
      fear behavior but had no effect on escape learning. Results reveal a novel role
      of the 5-HT(2C)R in the DS in the expression of instrumental escape deficits
      produced by uncontrollable stress and demonstrate that the involvement of 5
      HT(2C)R activation in stress-induced behaviors is regionally specific.

PMID- 21958864
TI  - The design and delivery of a thermally responsive peptide to inhibit S100B
      mediated neurodegeneration.
AB  - S100B, a glial-secreted protein, is believed to play a major role in
      neurodegeneration in Alzheimer's disease, Down syndrome, traumatic brain injury,
      and spinocerebellar ataxia type 1 (SCA1). SCA1 is a trinucleotide repeat disorder
      in which the expanded polyglutamine mutation in the protein ataxin-1 primarily
      targets Purkinje cells of the cerebellum. Currently, the exact mechanism of S100B
      mediated Purkinje cell damage in SCA1 is not clear. However, here we show that
      S100B may act via the activation of the receptor for advanced glycation end
      product (RAGE) signaling pathway, resulting in oxidative stress-mediated injury
      to mutant ataxin-1-expressing neurons. To combat S100B-mediated
      neurodegeneration, we have designed a selective thermally responsive S100B
      inhibitory peptide, Synb1-ELP-TRTK. Our therapeutic polypeptide was developed
      using three key elements: (1) the elastin-like polypeptide (ELP), a thermally
      responsive polypeptide, (2) the TRTK12 peptide, a known S100B inhibitory peptide,
      and (3) a cell-penetrating peptide, Synb1, to enhance intracellular delivery.
      Binding studies revealed that our peptide, Synb1-ELP-TRTK, interacts with its
      molecular target S100B and maintains a high S100B binding affinity as comparable
      with the TRTK12 peptide alone. In addition, in vitro studies revealed that Synb1
      ELP-TRTK treatment reduces S100B uptake in SHSY5Y cells. Furthermore, the Synb1
      ELP-TRTK peptide decreased S100B-induced oxidative damage to mutant ataxin-1
      expressing neurons. To test the delivery capabilities of ELP-based therapeutic
      peptides to the cerebellum, we treated mice with fluorescently labeled Synb1-ELP
      and observed that thermal targeting enhanced peptide delivery to the cerebellum.
      Here, we have laid the framework for thermal-based therapeutic targeting to
      regions of the brain, particularly the cerebellum. Overall, our data suggest that
      thermal targeting of ELP-based therapeutic peptides to the cerebellum is a novel
      treatment strategy for cerebellar neurodegenerative disorders.

PMID- 21958865
TI  - GABA(B) receptors accentuate neural excitation contrast in rat insular cortex.
AB  - Synaptic transmission mediated by metabotropic GABA receptors, GABA(B) receptors,
      regulates physiological functions of cerebrocortical local circuits. It is,
      however, still unknown how GABA(B) receptors regulate excitatory propagation at
      more macroscopic level. We performed in vivo optical imaging to investigate the
      spatio-temporal profiles of GABA(B) receptor-mediated regulation of excitatory
      propagation in anesthetized rat insular cortex (IC). Repetitive electrical
      stimulation (a sequence of 10 pulses at 50 Hz) of the dysgranular IC (DI), a part
      of gustatory cortex (GC), elicited excitatory propagation along the rhinal
      fissure. Tonic activation of GABA(B) receptors by application of baclofen
      suppressed the optical signal amplitude to the early pulses in the sequence
      (first to third stimuli), typically in the rostral GC (rGC). In contrast, optical
      signal amplitude to later pulses was enhanced by baclofen in both the rGC and
      caudal GC (cGC). Baclofen reduced the area of excitation during the early pulses
      in the sequence but not during later pulses. Application of CGP 52432, which
      blocked GABA(B) receptor-mediated tonic and phasic inhibition, slightly
      suppressed optical responses to early pulses (though not to the first pulse),
      whereas it enhanced responses to later pulses, especially in the dorsolateral
      orbital cortex (DLO). Decay amplitude of the response to the first pulse was
      reversed to a large rise in amplitude by the GABA(A) receptor antagonist
      bicuculline. The decay amplitude was enhanced by CGP 52432 and reversed to a
      small rise by baclofen. This suggests that GABA(B) receptor activation reduced
      postsynaptic GABA(A) receptor activation indirectly via inhibition of presynaptic
      GABA release. Optical responses induced by DLO stimulation were reduced by pre
      stimulation of the cGC 180 ms before DLO stimulation, which was blocked by CGP
      52432. These results suggest that tonic and phasic activation of GABA(B)
      receptors cooperatively enhances the contrast of neural excitation at a level of
      millimeters.

PMID- 21958866
TI  - Semantic violation effect on object-related action comprehension. N400-like event
      related potentials for unusual and incorrect use.
AB  - The present study examined the specific action-sentence compatibility effect. We
      examined the action representation and semantic processes indexed by event
      related potentials (ERPs, N400 effect) when plausible or implausible actions were
      performed within a dynamic context (video tapes showing a sequence of four action
      frames). Two different semantic anomalies were reproduced in the final action
      frame, which consisted of an object that did not have the semantic properties
      required (functionally unusual) for the action goal (Experiment 1) or an object
      that was incorrectly used with regard to the instrumental properties required for
      the target action (Experiment 2). Fifteen participants performed an explicit task
      to distinguish congruous from incongruous actions for the final action frame. The
      ERP analysis showed a significant N400-like effect that was frontally distributed
      in response to incongruous conditions for both Experiment 1 and 2. Similarly,
      response times (RTs) increased in response to incongruous actions. Nevertheless,
      a temporo-parietal cortical distribution was more prevalent in the unusual object
      action representation (Experiment 1) than in the incorrect object-action
      representation (Experiment 2). These results may be explained by assuming that in
      Experiment 1, the relationship between the action and its intentional goals was
      violated, with a cortical-specific temporo-parietal response, whereas in
      Experiment 2 the intentional goal to perform the action was not violated. It can
      be argued that the N400-like effect was similar to the N400, which is generally
      evoked by linguistic stimuli, and these results suggest that N400 increases as
      the difficulty in accessing the semantic memory increases.

PMID- 21958868
TI  - Sleep-waking discharge profiles of dorsal raphe nucleus neurons in mice.
AB  - We have recorded, for the first time, in non-anesthetized, head-restrained mice,
      a total of 407 single units throughout the dorsal raphe nucleus (DR), which
      contains serotonin (5-hydroxytryptamine, 5-HT) neurons, during the complete wake
      sleep cycle. The mouse DR was found to contain a large proportion (52.0%) of
      waking (W)-active neurons, together with many sleep-active (24.8%) and
      W/paradoxical sleep (PS)-active (18.4%) neurons and a few state-unrelated neurons
      (4.7%). The W-active, W/PS-active, and sleep-active neurons displayed a biphasic
      narrow or triphasic broad action potential. Of the 212 W-active neurons, 194 were
      judged serotonergic (5-HT W-active neurons) because of their triphasic long
      duration action potential and low rate of spontaneous discharge, while the
      remaining 18 were judged non-serotonergic (non-5-HT W-active neurons) because of
      their biphasic narrow action potential and higher rate of spontaneous discharge.
      The 5-HT W-active neurons were subdivided into four groups, types I, II, III, and
      IV, on the basis of differences in firing pattern during wake-sleep states, their
      waking selectivity of discharge being in the order type I>type II>type III>type
      IV. During the transition from sleep to waking, the vast majority of waking
      specific or waking-selective type I and II neurons discharged after onset of
      waking, as seen with non-5-HT W-specific neurons. Triphasic DR W/PS-active
      neurons were characterized by a low rate of spontaneous discharge and a similar
      distribution to that of tyrosine hydroxylase-immunoreactive, dopaminergic
      neurons. Triphasic DR slow-wave sleep (SWS)-active and SWS/PS neurons were also
      characterized by slow firing. At the transition from sleep to waking, sleep
      selective neurons with no discharge activity during waking ceased firing before
      onset of waking, while, at the transition from waking to sleep, they fired after
      onset of sleep. The present study shows a marked heterogeneity and functional
      topographic organization of both serotonergic and non-serotonergic mouse DR
      neurons and suggests that they play different roles in behavioral state control
      and the sleep/waking switch.

PMID- 21958867
TI  - Delta oscillations induced by ketamine increase energy levels in sleep-wake
      related brain regions.
AB  - Neuronal signaling consumes much of the brain energy, mainly through the
      restoration of the membrane potential (MP) by ATP-consuming ionic pumps. We have
      reported that, compared with waking, ATP levels increase during the initial hours
      of natural slow-wave sleep, a time with prominent electroencephalogram (EEG)
      delta oscillations (0.5-4.5 Hz). We have hypothesized that there is a delta
      oscillation-ATP increase coupling, since, during delta waves, neurons exhibit a
      prolonged hyperpolarizing phase followed by a very brief phase of action
      potentials. However, direct proof of this hypothesis is lacking, and rapid
      changes in EEG/neuronal activity preclude measurement in the naturally sleeping
      brain. Thus, to induce a uniform state with pure delta oscillations and one
      previously shown to be accompanied by a similar pattern of neuronal activity
      during delta waves as natural sleep, we used ketamine-xylazine treatment in rats.
      We here report that, with this treatment, the high-energy molecules ATP and ADP
      increased in frontal and cingulate cortices, basal forebrain, and hippocampus
      compared with spontaneous waking. Moreover, the degree of ATP increase positively
      and significantly correlated with the degree of EEG delta activity. Supporting
      the hypothesis of decreased ATP consumption during delta activity, the ATP
      consuming Na+-K+-ATPase mRNA levels were significantly decreased, whereas the
      mRNAs for the ATP-producing cytochrome c oxidase (COX) subunits COX III and COX
      IVa were unchanged. Taken together, these data support the hypothesis of a
      cortical delta oscillation-dependent reduction in ATP consumption, thus providing
      the brain with increased ATP availability, and likely occurring because of
      reduced Na+-K+-ATPase-related energy consumption.

PMID- 21958869
TI  - Transplacental transfer of oseltamivir and its metabolite using the human
      perfused placental cotyledon model.
AB  - OBJECTIVE: Given the lack of data regarding the use of oseltamivir (Tamiflu)
      during pregnancy, we aimed to evaluate the placental transfer of oseltamivir
      phosphate and its active metabolite oseltamivir carboxylate, using the perfused
      placental cotyledon model. STUDY DESIGN: Cotyledons were coperfused with
      oseltamivir phosphate and oseltamivir carboxylate using the maximal
      concentrations described with a 75 mg, twice-daily oral dose. Main transfer
      parameters such as fetal transfer rate (FTR) and clearance index (CI) were
      assessed. RESULTS: Five placentas were coperfused with oseltamivir phosphate and
      oseltamivir carboxylate. The median FTR of oseltamivir phosphate was 8.5% (range,
      5.0-11.6%) and the median CI was 0.3 (range, 0.2-0.6). Regarding oseltamivir
      carboxylate transplacental transfer, the median FTR was 6.6% (range, 3.9-9.7%),
      whereas the median CI was 0.2 (range, 0.2-0.5). CONCLUSION: A transplacental
      transfer of oseltamivir phosphate and its metabolite oseltamivir carboxylate was
      detected and might have clinical relevance. Clinicians should be encouraged to
      report oseltamivir treatment outcomes during pregnancy.

PMID- 21958870
TI  - C(5) modified uracil derivatives showing antiproliferative and erythroid
      differentiation inducing activities on human chronic myelogenous leukemia K562
      cells.
AB  - The K562 cell line has been proposed as a useful experimental system to identify
      anti-tumor compounds acting by inducing terminal erythroid differentiation. K562
      cells exhibit a low proportion of hemoglobin-synthesizing cells under standard
      cell growth conditions, but are able to undergo terminal erythroid
      differentiation when treated with a variety of anti-tumor compounds. In this
      paper we report a screening study on a set of different modified C(5) uracil
      derivatives for the evaluation of their antiproliferative effect in connection
      with erythroid differentiation pathways, and for defining a new class of drug
      candidates for the treatment of chronic myelogenous leukemia. Activity of the
      derivatives tested can be classified in two effect: an antiproliferative effect
      linked to a high level of erythroid differentiation activity and an
      antiproliferative effect without activation of gamma globin genes The highest
      antiproliferative effect and erythroid induction was shown by compound 9, a
      thymine derivative bearing a n-octyl chain on nitrogen N(1), whereas thymine did
      not show any effect, suggesting the importance of the linear alkyl chain in
      position N(1). To our knowledge this compound should be considered among the most
      efficient inducers of erythroid differentiation of K562 cells. This work is the
      starting point for the quest of more effective and specific drugs for the
      induction of terminal erythroid differentiation, for leading new insights in the
      treatment of neoplastic diseases with molecules acting by inducing
      differentiation rather than by simply exerting cytotoxic effects.

PMID- 21958871
TI  - Involvement of Chk1-Cdc25A-cyclin A/CDK2 pathway in simvastatin induced S-phase
      cell cycle arrest and apoptosis in multiple myeloma cells.
AB  - Statins have been demonstrated to effectively inhibit proliferation and induce
      apoptosis in cancer cells by inhibition of geranylgeranylation, however its novel
      molecular mechanism remains to be determined. Recently simvastatin has been found
      to result in the synergistic induction of apoptosis with 7-hydroxystaurosporine
      (UCN-01) (a Chk1 inhibitor) in myeloma cells. Therefore we hypothesized that Chk1
      plays a role in the anti-myeloma effect of simvastatin. Interestingly, we found
      that simvastatin caused a dose-dependent increase in S phase cell cycle and
      induced significant apoptosis. The results of western blot showed that
      simvastatin-induced S-phase cell cycle arrest was associated with activation of
      Chk1, downregulation of Cdc25A, cyclin A and CDK2 expression. Additionally,
      simvastatin-induced apoptosis was accompanied by diminished Bcl-2 protein
      expression, increased cytosolic cytochrome c level, and activation of caspase 9
      and caspase 3. Further investigation revealed that silence of Chk1 expression by
      Chk1 specific siRNA inhibited simvastatin-induced activation of Chk1,
      downregulation of Cdc25A, cyclin A and CDK2 expression, and diminished S phase
      cell cycle arrest. Additionally, inhibition of Chk1 expression enhanced
      simvastatin-induced downregulation of Bcl-2, caspase 9 cleavage and subsequent
      apoptosis. These results suggested that the Chk1-Cdc25A-cyclin A/CDk2 pathway was
      involved in simvastatin-induced S-phase cell cycle arrest and apoptosis in
      multiple myeloma cell lines.

PMID- 21958872
TI  - Knockdown of the tachykinin neurokinin 1 receptor by intrathecal administration
      of small interfering RNA in rats.
AB  - The contribution of tachykinin neurokinin 1 (NK1) receptor to nociceptive
      processing in the dorsal horn has been evaluated by tachykinin NK1 receptor
      antagonism and knockout or knockdown of tachykinin NK1 receptor; however, these
      results have not always been consistent. Therefore, to reevaluate the role of
      tachykinin NK1 receptor in the dorsal horn, a solution of hemagglutinating virus
      of the Japan envelope (HVJ-E) with small interfering RNA (siRNA) against
      tachykinin NK1 receptor was administered intrathecally and then the effect of
      treatment on tachykinin NK1 receptor immunohistochemistry and on the induction of
      inflammation, thermal hyperalgesia and scratching behavior was evaluated. This
      treatment resulted in marked reduction of tachykinin NK1 receptor
      immunoreactivity through the spinal dorsal horn, and the induction of thermal
      hyperalgesia and scratching behavior by substance P was significantly attenuated
      in rats with tachykinin NK1 receptor siRNA. In addition, only one intrathecal
      injection of tachykinin NK1 receptor siRNA reduced carrageenan-induced
      inflammation and thermal hyperalgesia significantly and markedly attenuated the
      induction of flinching after formalin injection and c-Fos expression in the
      dorsal horn following formalin injection. The efficient down-regulation of
      tachykinin NK1 receptor by intrathecal administration tachykinin NK1 receptor
      siRNA suggests that this method may be a valuable tool for examining the function
      of genes expressed in the dorsal horn.

PMID- 21958873
TI  - Anatabine lowers Alzheimer's Abeta production in vitro and in vivo.
AB  - Brain Abeta accumulation represents a key pathological hallmark in Alzheimer's
      disease. In this study, we investigated the impact of anatabine, a minor alkaloid
      present in plants of the Solanacea family on Abeta production in vitro using a
      cell line overexpressing the human amyloid precursor protein (APP) and in vivo
      using a transgenic mouse model of Alzheimer's disease. In vitro, anatabine lowers
      Abeta1-40 and Abeta1-42 levels in a dose dependent manner and reduces sAPPbeta
      production without impacting sAPPalpha levels suggesting that anatabine lowers
      Abeta production by mainly impacting the beta-cleavage of APP. Additionally, we
      show that anatabine lowers NFkappaB activation at doses that inhibit Abeta
      production in vitro. Since NFkappaB is known to regulate BACE-1 expression (the
      rate limiting enzyme responsible for Abeta production), we determined the impact
      of anatabine on BACE-1 transcription. We show that anatabine inhibits BACE-1
      transcription and reduces BACE-1 protein levels in human neuronal like SHSY-5Y
      cells suggesting that the Abeta lowering properties of anatabine are mediated via
      a regulation of BACE-1 expression. In vivo, we show that an acute treatment with
      anatabine for four days significantly lowers brain soluble Abeta1-40 and Abeta1
      42 levels in a transgenic mouse model of Alzheimer's disease. Altogether our data
      suggest that anatabine may represent an interesting compound for regulating brain
      Abeta accumulation.

PMID- 21958874
TI  - Antiatherogenic effects of oleanolic acid in apolipoprotein E knockout mice.
AB  - Oleanolic acid (OA) is a plant triterpenoid steroid with potentially
      antiatherogenic properties. We investigated whether OA affected atherosclerosis
      development and vascular function in apolipoprotein E knockout (ApoE(-/-)) mice.
      ApoE(-/-) mice were fed a high cholesterol Western-type diet in combination with
      OA (100 mg/kg/day), fluvastatin (5 mg/kg/day) or vehicle, with wild type (WT)
      mice serving as controls. After 8 weeks of treatment atherosclerotic plaque areas
      in the aortic arch and plasma lipid concentrations were determined.
      Vasoconstriction and relaxation of the proximal part of aorta were investigated
      in vitro. Inducible nitric oxide synthase (iNOS) was visualized using
      immunoblotting. As opposed to WT and fluvastatin- and vehicle-treated mice, OA
      fed ApoE(-/-) mice gained no weight during the treatment period. Plasma
      concentrations of total-cholesterol and triglyceride were not significantly
      reduced by OA- or fluvastatin treatment. Plaque area of vehicle-treated mice was
      25%, but only 14% in OA- and 19% in fluvastatin-treated mice. As compared to WT,
      vasoconstriction to phenylephrine was attenuated in ApoE(-/-) mice. The NOS
      inhibitor asymmetric dimethylarginine (ADMA) enhanced phenylephrine constriction,
      but significantly more so in vehicle- and fluvastatin-treated than in OA-treated
      and WT mice. Relaxation to acetylcholine was only slightly attenuated in ApoE(-/
      ) mice and not affected by OA or fluvastatin treatment. ADMA abolished
      acetylcholine relaxation almost completely. In ApoE(-/-) mice iNOS expression was
      reduced by OA treatment. In conclusion OA exerts potent antiatherogenic effects
      independent of plasma lipid levels and without major changes in eNOS-mediated
      acetylcholine relaxation. However, OA reduced iNOS expression possibly altering
      vascular reactivity to phenylephrine.

PMID- 21958875
TI  - Vascular contribution of adrenomedullin to microcirculatory improvement in
      experimental colitis.
AB  - The effect of adrenomedullin (AM), a peptide that has demonstrated vasodilatory
      activity, was studied in the colon and small mesenteric arteries of rats in a
      chronic model of inflammatory bowel disease. AM (50 ng/kg/day) was administered
      i.p. daily, starting 24h after trinitrobenzensulfonic acid (TNBS, 30 mg)
      instillation. After 14 days, rats were sacrificed, colons were macroscopically
      analyzed and biochemical parameters (myeloperoxidase activity, cytokines,
      cyclooxygenase-2 (COX-2) as well as inducible nitric oxide synthase (iNOS)
      expression) were determined. Vascular function of small mesenteric arteries was
      assessed by addition of phenylephrine (10-8 to 10-4 mol/L) and participation of
      COX and NOS pathways was also evaluated by using different inhibitors:
      indomethacin, NS-398, L-NNA, and 1400 w. Chronic AM treatment significantly
      reduced colonic macroscopic damage and inflammation markers. TNBS instillation
      induced COX-2 and iNOS expressions in colon and small mesenteric arteries; AM
      treatment decreased COX-2 expression only in microvessels from rats with colitis.
      An attenuation of phenylephrine-induced contraction was detected in small
      mesenteric arteries from both TNBS and AM-treated rats. COX and NOS inhibitors
      altered the contractile ability of phenylephrine in small mesenteric arteries
      from TNBS rats, suggesting the involvement of COX-2 and iNOS derived factors in
      the deleterious effect of TNBS on vascular reactivity; AM administration was able
      to reduce such alteration. Finally, treatment with the peptide significantly
      reduced colonic nitric oxide (NO) levels, without affecting plasma concentration.
      In conclusion, AM showed beneficial effects in the restoration of vascular
      function through the regulation of vasoactive products derived from COX-2 and
      iNOS.

PMID- 21958876
TI  - A biochemical, electrocardiographic, electrophoretic, histopathological and in
      vitro study on the protective effects of (-)epicatechin in isoproterenol-induced
      myocardial infarcted rats.
AB  - (-) Epicatechin rich foods and (-) epicatechin improve cardiovascular function.
      Consumption of diets rich in flavonoids is associated with reduced risk of
      cardiovascular diseases. Oxidative stress resulting from increased production of
      free radicals associated with decreased levels of antioxidants in the myocardium
      plays a major role in the pathogenesis of myocardial infarction. This study aims
      to evaluate the preventive effects of (-) epicatechin on oxidative stress in
      isoproterenol-induced myocardial infarcted rats. Male Wistar rats were pretreated
      with (-) epicatechin (20mg/kg body weight) daily for 21 days. After pretreatment,
      isoproterenol (100mg/kg body weight) was injected into the rats at an interval of
      24h for two days to induce myocardial infarction. Isoproterenol induced rat's
      electrocardiogram showed elevated ST segments and significant increase in the
      activity of serum creatine kinase-MB, level of serum troponin-T and increased
      intensities of serum lactate dehydrogenase 1 and 2-isoenzymes. The rats also
      showed significant increased levels of heart lipid peroxidation products and
      significant decreased activities of heart superoxide dismutase, catalase,
      glutathione peroxidase, glutathione reductase and levels of reduced glutathione.
      Pretreatment with (-) epicatechin revealed significant protective effects on all
      the biochemical parameters and electrocardiogram investigated. Histopathology of
      myocardium confirmed the present findings. The in vitro study on the effects of (
      ) epicatechin on scavenging free radical 1,1-diphenyl-2-picrylhydrazyl revealed
      the free radical scavenging potential of (-) epicatechin. Thus, (-) epicatechin
      exerts protective effects against isoproterenol-induced oxidative stress thereby
      reducing cardiac tissue damage by its free radical scavenging and antioxidant
      effects.

PMID- 21958877
TI  - Metformin regulates hepatic lipid metabolism through activating AMP-activated
      protein kinase and inducing ATGL in laying hens.
AB  - Although many clinical trials have showed that metformin improves non-alcoholic
      fatty liver disease, which is a common liver disease associated with hepatic
      enzyme abnormalities, an animal model is required to investigate the effects of
      altered gene expression and post-translational processing (proteins) in mediating
      the observed responses. Laying hens appear to develop fatty livers, as in the
      case in human beings, when ingesting energy in excess of maintenance, and they
      can be used as an animal model for observing hepatic steatosis. The aim of this
      study was to investigate whether metformin could improve the non-alcoholic fatty
      liver of laying hens and to examine the possible mechanisms of lipid-lowering
      effects. Forty-eight Leghorn laying hens of Hy-Line variety W-36 - 44 weeks with
      64.8% hen-day egg production - were randomly assigned into 4 treatments, each
      receiving 0, 10, 30, or 100mg of metformin with saline per kg body weight by
      daily wing vein injection. Results showed that, compared with the control,
      significant decreases existed in the laying rates; plasma triglyceride,
      cholesterol, and insulin levels; body weights; abdominal fat weights; hepatic
      lipid contents; and hepatic fatty acid synthase expression of layers receiving 30
      or 100mg per kg body weight, whereas significant increases in their hepatic
      5'adenosine monophosphate-activated protein kinase, acyl-CoA carboxylase
      phosphorylation, adipose triglyceride lipase, and carnitine palmitoyl transferase
      1 expression were observed. These data suggest that metformin could reduce lipid
      deposits in the liver and that the laying hen is a valuable animal model for
      studying hepatic steatosis.

PMID- 21958878
TI  - In vitro and in vivo pharmacological characterisation of the potent and selective
      vasopressin V(1A) receptor antagonist 4-[4-(4-Chloro-phenyl)-5-[1,2,3]triazol-2
      ylmethyl-4H-[1,2,4]triazol-3-yl]-piperidin-1-yl-(3,5-difluoro-phenyl) methanone
      (PF-00738245).
AB  - The dysregulation of arginine vasopressin (AVP) release and activation of
      vasopressin receptors plays an important role in disease conditions including
      polycystic kidney disease, congestive heart failure and dysmenorrhoea. The
      development of potent and selective vasopressin receptor ligands is needed to
      help dissect the function of the specific subtypes in disease pathogenesis. Here
      we report the pharmacological characterisation of PF-00738245 in in vitro binding
      and functional assays using cells expressing vasopressin V(1A), V(1B) or V2
      receptors. PF-00738245 inhibited AVP binding to the recombinant human vasopressin
      V(1A) receptor (K(i)=2.85 nM) and blocked AVP-induced rat aortic ring and human
      myometrial contraction (pK(B)=7.35 and 8.62 respectively). PF-00738245 was
      selective for the vasopressin V(1A) receptor by demonstrating minimal binding to
      vasopressin V(1B) (3.6% inhibition at 10 MUM) or functional activity at
      vasopressin V2 receptors (8.1% agonist and -8.4% antagonist activity at 10 MUM)
      as well as the oxytocin receptor (46.3% antagonist activity at 10 MUM). The in
      vivo pharmacological properties were tested orally in the rat and PF-00738245
      dose dependently blocked the effect of AVP on a capsaicin-induced cutaneous flare
      response. Taken together the data support the use of PF-00738245 as a potent and
      selective vasopressin V(1A) receptor antagonist which may have utility in the
      treatment of disease conditions which are propagated by elevation in vasopressin
      V(1A) receptor signalling.

PMID- 21958879
TI  - Blood flow in the foetal superior vena cava and the effect of foetal breathing
      movements.
AB  - OBJECTIVES: The superior vena cava (SVC) drains venous blood from the upper
      foetal body, mainly the head. Data on the human foetus is scarce. Here we present
      reference values for the blood flow during the second half of pregnancy, and test
      the hypothesis that foetal breathing movements (FBM) enhance this flow. METHODS:
      Based on a power calculation, 110 women with low-risk singleton pregnancies were
      recruited to a longitudinal study that included three sets of observations during
      the second half of pregnancy. Ultrasound was used to determine inner diameter,
      peak systolic blood velocity and time-average maximum velocities in the SVC
      during rest and respiratory activity. RESULTS: During the second half of
      pregnancy, SVC blood flow increased from 57.8 mL/min (95% CI 51.7-64.3) to 221.5
      (204.5-239.3). Based on 558 sets of observations obtained during foetal rest and
      FBM, we found an overall increase in diameter from 0.41 cm (0.40-0.42) to 0.46
      (0.44-0.48), peak systolic velocity from 35.9 cm/s (34.9-37.0) to 62.2 (59.1
      65.5), and time-averaged maximum velocity from 20.3 cm/s (19.7-20.8) to 27.3
      (26.1-28.6). This resulted in an overall 90% increase in mean SVC blood flow,
      from 108.1 mL/min (98.8-117.9) at rest to 205.9 (183.2-230.5) during FBM.
      CONCLUSION: The blood flow in the SVC increases during the second half of
      pregnancy and is substantially augmented during FBM. Since high-amplitude FBM
      additionally reduces flow in the inferior vena cava, the net effect is a
      prioritised venous drainage from the foetal head enhancing the washout of CO(2)
      in that area, which also contains the chemoreceptors.

PMID- 21958880
TI  - Co-administration of raltegravir reduces daily darunavir exposure in HIV-1
      infected patients.
AB  - The potential drug-to-drug interaction between darunavir and raltegravir in the
      setting of HIV infection is a highly debated issue still unresolved. In the
      present study we have evaluated the pharmacokinetics of darunavir and ritonavir
      in 53 HIV-1 infected patients with or without concomitant raltegravir
      administration. The assessment of trough plasma drug concentrations was carried
      out in all subjects and the potential influence of raltegravir on darunavir and
      ritonavir disposition, assessed by specific pharmacokinetic evaluations in a
      subgroup of 25 patients. No significant differences on darunavir and ritonavir
      plasma trough levels were observed between patients receiving or not raltegravir.
      Co-administration of raltegravir was, however, associated with a 40% reduction in
      darunavir C(max) and estimated AUC(0-24), as well a 60% increase in the estimated
      darunavir clearance compared with values measured in patients not given
      raltegravir. Notably, this interaction was independent of the dosage of darunavir
      and not due to effects of raltegravir on the pharmacokinetics of ritonavir. These
      results should be taken into account when darunavir-based regimens are
      implemented in the setting of HIV, especially considering that this drug is
      usually administered at fixed daily dose and no therapeutic drug monitoring is
      performed in most centres.

PMID- 21958881
TI  - Vitamin D and cardiovascular disease will it live up to its hype?
AB  - Substantial evidence suggests that a large portion of the population have
      suboptimal levels of vitamin D, which may adversely affect the cardiovascular
      (CV) system, including increasing levels of parathyroid hormone, activating the
      renin-angiotensin-aldosterone system, and increasing insulin resistance, thus
      leading to hypertension and left ventricular hypertrophy, metabolic
      syndrome/diabetes mellitus, systemic inflammation, and increased risk of
      atherosclerosis and CV disease events. We review the evidence that vitamin D
      deficiency is associated with incident CV disease events, as well as evidence
      that vitamin D supplementation is associated with reduction in CV diseases.
      Although the current evidence has created substantial hype, randomized controlled
      trials are needed to determine whether routine vitamin D assessment and
      supplementation will improve CV outcomes.

PMID- 21958883
TI  - Trade-offs and toss-ups: making revascularization decisions in carotid artery
      disease.

PMID- 21958882
TI  - Health-related quality of life after carotid stenting versus carotid
      endarterectomy: results from CREST (Carotid Revascularization Endarterectomy
      Versus Stenting Trial).
AB  - OBJECTIVES: The purpose of this study was to compare health-related quality of
      life (HRQOL) outcomes in patients treated with carotid artery stenting (CAS)
      versus carotid endarterectomy (CEA). BACKGROUND: In CREST (Carotid
      Revascularization Endarterectomy versus Stenting Trial), the largest randomized
      trial of carotid revascularization to date, there was no significant difference
      in the primary composite endpoint, but rates of stroke and myocardial infarction
      (MI) differed between CAS and CEA. To help guide individualized clinical decision
      making, we compared HRQOL among patients enrolled in the CREST study. We also
      performed exploratory analyses to evaluate the association between periprocedural
      complications and HRQOL. METHODS: We measured HRQOL at baseline, and after 2
      weeks, 1 month, and 1 year among 2,502 patients randomly assigned to either CAS
      or CEA in the CREST study. The HRQOL was assessed using the Medical Outcomes
      Study Short-Form 36 (SF-36) and 6 disease-specific scales designed to study HRQOL
      in patients undergoing carotid revascularization. RESULTS: At both 2 weeks and 1
      month, CAS patients had better outcomes for multiple components of the SF-36,
      with large differences for role physical function, pain, and the physical
      component summary scale (all p < 0.01). On the disease-specific scales, CAS
      patients reported less difficulty with driving, eating/swallowing, neck pain, and
      headaches but more difficulty with walking and leg pain (all p < 0.05). However,
      by 1 year, there were no differences in any HRQOL measure between CAS and CEA. In
      the exploratory analyses, periprocedural stroke was associated with poorer 1-year
      HRQOL across all SF-36 domains, but periprocedural MI or cranial nerve palsy were
      not. CONCLUSIONS: Among patients undergoing carotid revascularization, CAS is
      associated with better HRQOL during the early recovery period as compared with
      CEA-particularly with regard to physical limitations and pain-but these
      differences diminish over time and are not evident after 1 year. Although CAS and
      CEA are associated with similar overall HRQOL at 1 year, event-specific analyses
      confirm that stroke has a greater and more sustained impact on HRQOL than MI.
      (Carotid Revascularization Endarterectomy versus Stenting Trial [CREST];
      NCT00004732)

PMID- 21958885
TI  - The magic of disappearing stents.

PMID- 21958884
TI  - Evaluation of the second generation of a bioresorbable everolimus-eluting
      vascular scaffold for the treatment of de novo coronary artery stenosis: 12-month
      clinical and imaging outcomes.
AB  - OBJECTIVES: The aim of this study was to demonstrate that the prevention of early
      scaffold area shrinkage of the ABSORB BVS (Rev.1.1, Abbott Vascular, Santa Clara,
      California) was sustained and not simply delayed by a few months. BACKGROUND:
      With improved scaffold design and modified manufacturing process of its polymer,
      the second iteration of ABSORB (BVS 1.1) has improved performance to prevent a
      scaffold area reduction at 6 months. METHODS: Fifty-six patients were enrolled
      and received 57 ABSORB scaffolds. Quantitative coronary angiography,
      intravascular ultrasound (IVUS), analysis of radiofrequency backscattering,
      echogenicity and optical coherence tomography (OCT) were performed at baseline
      and at 12-month follow-up. RESULTS: Overall the scaffold area remained unchanged
      with IVUS as well as with OCT, whereas the radiofrequency backscattering and the
      echogenicity of the struts decreased by 16.8% (p < 0.001) and 20% (p < 0.001),
      respectively; more specifically, the strut core area on OCT decreased by 11.4% (p
      = 0.003). Despite the absence of scaffold area loss, pharmacological vasomotion
      was restored. On an intention-to-treat basis, the angiographic late lumen loss
      amounted to 0.27 +/- 0.32 mm with an IVUS relative decrease in minimal lumen area
      of 1.94% (p = 0.12), without significant changes in mean lumen area. The OCT at
      follow-up showed that 96.69% of the struts were covered and that malapposition,
      initially observed in 18 scaffolds was only detected at follow-up in 4 scaffolds.
      Two patients experienced peri-procedural and iatrogenic myocardial infarction,
      respectively, whereas 2 underwent repeat intervention, resulting in the major
      adverse cardiac event rate of 7.1% (4 of 56). CONCLUSIONS: The 12-month
      performance of the second-generation ABSORB bioresorbable everolimus-eluting
      scaffold justifies the conduct of a randomized trial against current best
      standards. (A Clinical Evaluation of the Bioabsorbable Everolimus Eluting
      Coronary Stent System [BVS EECSS] in the Treatment of Patients With de Novo
      Native Coronary Artery Lesions; NCT00856856).

PMID- 21958886
TI  - Outcome comparison of 600- and 300-mg loading doses of clopidogrel in patients
      undergoing primary percutaneous coronary intervention for ST-segment elevation
      myocardial infarction: results from the ARMYDA-6 MI (Antiplatelet therapy for
      Reduction of MYocardial Damage during Angioplasty-Myocardial Infarction)
      randomized study.
AB  - OBJECTIVES: The purpose of this study was to compare 600- and 300-mg clopidogrel
      loading doses in patients with ST-segment elevation myocardial infarction
      (STEMI). BACKGROUND: Given the high thrombotic risk of patients with STEMI,
      greater platelet inhibition may improve outcome in those patients receiving
      percutaneous coronary intervention (PCI). Although observational data suggest
      that pretreatment with a 600-mg clopidogrel loading dose may be more effective
      than the 300-mg regimen in primary PCI, this hypothesis has never been tested in
      a randomized study. METHODS: A total of 201 patients undergoing primary PCI for
      STEMI randomly received a 600-mg (n = 103) or 300-mg (n = 98) clopidogrel loading
      dose before the procedure. The primary endpoint was the evaluation of the infarct
      size, defined as the area under the curve of cardiac markers. RESULTS: Infarct
      size was significantly lower in the high-dose regimen: median creatine kinase
      myocardial band 2,070 ng/ml (interquartile range [IQR]: 815 to 2,847 ng/ml)
      versus 3,049 ng/ml (IQR: 1,050 to 7,031 ng/ml) in the 300-mg group, p = 0.0001;
      troponin-I 255 ng/ml (IQR: 130 to 461 ng/ml) versus 380 ng/ml (IQR: 134 to 1,406
      ng/ml), p < 0.0001. In the 600-mg arm, Thrombolysis In Myocardial Infarction flow
      grade <3 after PCI was less frequent (5.8% vs. 16.3%, p = 0.031), left
      ventricular ejection fraction at discharge was improved (52.1 +/- 9.5% vs. 48.8
      +/- 11.3%, p = 0.026), 30-day major adverse cardiovascular events were fewer
      (5.8% vs. 15%, p = 0.049), and bleeding/entry site complications were not
      increased (secondary endpoints). CONCLUSIONS: In STEMI patients, pre-treatment
      with a 600-mg clopidogrel loading dose before primary PCI was associated with a
      reduction of the infarct size compared with a 300-mg loading dose, as well as
      with improvement of angiographic results, residual cardiac function, and 30-day
      major adverse cardiovascular events; further studies are warranted to evaluate
      impact of such strategy on survival.

PMID- 21958887
TI  - Chronic kidney disease and risk for presenting with acute myocardial infarction
      versus stable exertional angina in adults with coronary heart disease.
AB  - OBJECTIVES: The aim of this study was to examine whether kidney dysfunction is
      associated with the type of clinical presentation of coronary heart disease
      (CHD). BACKGROUND: Reduced kidney function increases the risk for developing CHD,
      but it is not known whether it also influences the acuity of clinical
      presentation, which has important prognostic implications. METHODS: A case
      control study was conducted of subjects whose first clinical presentation of CHD
      was either acute myocardial infarction or stable exertional angina between
      October 2001 and December 2003. Estimated glomerular filtration rate (eGFR)
      before the incident event was calculated using calibrated serum creatinine and
      the abbreviated MDRD (Modification of Diet in Renal Disease) equation. Patient
      characteristics and use of medications were ascertained from self-report and
      health plan databases. Multivariable logistic regression was used to examine the
      association of reduced eGFR and CHD presentation. RESULTS: A total of 803 adults
      with incident acute myocardial infarctions and 419 adults with incident stable
      exertional angina who had baseline eGFRs <=130 ml/min/1.73 m(2) were studied.
      Mean eGFR was lower in subjects with acute myocardial infarctions compared with
      those with stable angina. Compared with eGFR of 90 to 130 ml/min/1.73 m(2), a
      strong, graded, independent association was found between reduced eGFR and
      presenting with acute myocardial infarction, with adjusted odds ratios of 1.36
      (95% confidence interval: 0.99 to 1.86) for eGFR 60 to 89 ml/min/1.73 m(2), 1.55
      (95% confidence interval: 0.92 to 2.62) for eGFR 45 to 59 ml/min/1.73 m(2), and
      3.82 (95% confidence interval: 1.55 to 9.46) for eGFR <45 ml/min/1.73 m(2) (p <
      0.001 for trend). CONCLUSIONS: An eGFR <45 ml/min/1.73 m(2) is a strong,
      independent predictor of presenting with acute myocardial infarction versus
      stable angina as the initial manifestation of CHD.

PMID- 21958888
TI  - Conformational change in coronary artery structure assessed by optical coherence
      tomography in patients with vasospastic angina.
AB  - OBJECTIVES: The aim of this study was to investigate the conformational change of
      arterial structure in the vasospastic lesion with optical coherence tomography.
      BACKGROUND: Coronary artery spasm plays an important role in the pathogenesis of
      ischemic heart diseases. The conformational change of each arterial layer during
      vasospasm has not been studied in detail. METHODS: We assessed 19 coronary
      arteries (10 spasm and 9 nonspasm lesions) with optical coherence tomography
      during the provocation test for coronary spasm. An intimal bump was defined as 1
      or more intimal projections into the lumen that disappeared after the
      administration of nitroglycerine (NTG). Intimal gathering was defined as a
      folding/gathering of the intima, resulting in multiple kinks in the luminal
      contour that resolved after the administration of NTG. RESULTS: The spasm lesion
      more frequently showed an intimal bump at baseline and intimal gathering during
      spasm compared with the nonspasm lesion (spasm 80% vs. nonspasm 0%, p < 0.01,
      spasm 100% vs. nonspasm 0%, p < 0.01, respectively). The spasm lesion
      demonstrated a thicker maximum media thickness (spasm 0.24 +/- 0.04 mm vs.
      nonspasm 0.12 +/- 0.03 mm, p < 0.01) at baseline, whereas no differences were
      observed after the administration of NTG (spasm 0.13 +/- 0.03 mm vs. nonspasm
      0.13 +/- 0.02 mm, p = 0.65). CONCLUSIONS: Our results suggest that medial
      contraction occurs even in an asymptomatic state and facilitates the formation of
      an intimal bump in patients with vasospastic angina. Luminal narrowing during
      spasm is associated with intimal gathering without alteration of intimal area.

PMID- 21958889
TI  - Left atrial contractile function following a successful modified Maze procedure
      at surgery and the risk for subsequent thromboembolic stroke.
AB  - OBJECTIVES: The aim of this study was to evaluate whether certain post-Maze left
      atrial (LA) contractile profiles may pose a risk for ischemic stroke. BACKGROUND:
      The mechanical contraction of the left atrium may be modified after the Maze
      procedure. Whether this imposes a risk for stroke, even in the presence of sinus
      rhythm and after removal of the LA appendage, is not known. METHODS: Clinical,
      surgery-related, and echocardiographic data from 150 patients who underwent
      radiofrequency and cryoablation Maze procedures without the use of atrial
      incisions between 2004 and 2009 and were in sustained sinus rhythm were collected
      and analyzed. The occurrence of stroke was evaluated by reviewing clinical
      records. All stroke events were adjudicated by a neurologist. RESULTS: At a mean
      follow-up time of 24.5 months, 15 patients (10%) had experienced ischemic
      strokes. Forty-seven patients (31%) had no evidence of LA mechanical contraction
      at 3 months after surgery (baseline assessment) and on follow-up
      echocardiography. Multivariate analysis showed that a lack of LA mechanical
      contraction at baseline was associated with a 5-fold increase in the risk for
      stroke (p = 0.02) during follow-up. Larger atria imposed a significant risk as
      well; LA volume index >=33 ml/m(2) was associated with a 3-fold risk increase (p
      = 0.03). These effects were maintained regardless of the lack of mechanical valve
      implantation and anticoagulation treatment. CONCLUSIONS: Absence of LA
      contraction and LA volume index >=33 ml/m(2) result in a significant increase in
      the risk for thromboembolic stroke after the Maze procedure for patients in sinus
      rhythm.

PMID- 21958890
TI  - Refining the assessment of stroke risk after the maze procedure.

PMID- 21958891
TI  - Left atrial compression and the mechanism of exercise impairment in patients with
      a large hiatal hernia.
AB  - OBJECTIVES: The purpose of this study was to determine the association between
      cardiac compression and exercise impairment in patients with a large hiatal
      hernia (HH). BACKGROUND: Dyspnea and exercise impairment are common symptoms of a
      large HH with unknown pathophysiology. Studies evaluating the contribution of
      cardiac compression to the pathogenesis of these symptoms have not been
      performed. METHODS: We collected clinical data from a consecutive series of 30
      patients prospectively evaluated with resting and stress echocardiography,
      cardiac computed tomography, and respiratory function testing before and after
      laparoscopic HH repair. Left atrial (LA), inferior pulmonary vein, and coronary
      sinus compression was analyzed in relation to exercise capacity (metabolic
      equivalents [METs] achieved on Bruce treadmill protocol). RESULTS: Exertional
      dyspnea was present in 25 of 30 patients (83%) despite normal mean baseline
      respiratory function. Moderate to severe LA compression was qualitatively present
      in 23 of 30 patients (77%) on computed tomography. Right and left inferior
      pulmonary vein and coronary sinus compression was present in 11 of 30 (37%), 12
      of 30 (40%), and 26 of 30 (87%) patients, respectively. Post-operatively, New
      York Heart Association functional class and exercise capacity improved
      significantly (number of patients in New York Heart Association functional
      classes I, II, III, and IV: 6, 11, 11, and 2 vs. 26, 4, 0, and 0, respectively, p
      < 0.001; METs [percentage predicted]: 75 +/- 24% vs. 112 +/- 23%, p < 0.001) and
      resolution of cardiac compression was observed. Absolute change in LA diameter on
      the echocardiogram was the only independent cardiorespiratory predictor of
      exercise capacity improvement post-operatively (p = 0.006). CONCLUSIONS: We
      demonstrate, for the first time, marked exercise impairment and cardiac
      compression in patients with a large HH and normal respiratory function. After HH
      repair, exercise capacity improves significantly and correlates with resolution
      of LA compression.

PMID- 21958892
TI  - When the stomach rules the heart: dyspnea as a neglected complication of a large
      hiatal hernia.

PMID- 21958894
TI  - President's page: measuring and other things.

PMID- 21958893
TI  - Comprehensive post-operative assessment of apico-aortic conduit for aortic
      stenosis with cardiac magnetic resonance imaging.

PMID- 21958896
TI  - Distinction of "fat around the heart".

PMID- 21958897
TI  - Medication adherence is not our problem?

PMID- 21958899
TI  - Measurement of adenoma detection and discrimination during colonoscopy in routine
      practice: an exploratory study.
AB  - BACKGROUND: Measuring neoplasia yield is a priority in the quality improvement
      process for colonoscopy. However, neither the most appropriate quality indicator
      nor the standard threshold has been established. OBJECTIVE: To determine the most
      appropriate quality indicators to assess the yield of routine colonoscopy.
      DESIGN: Retrospective. SETTING: Population-based colorectal cancer screening
      program in 3 French administrative areas. SUBJECTS: One hundred
      gastroenterologists and their average-risk asymptomatic patients aged 50 to 74
      years undergoing colonoscopy for positive guaiac-based fecal occult blood test
      results. MAIN OUTCOME MEASUREMENTS: Comparison of several indicators, mainly the
      adenoma detection rate (ADR) and polyp detection rate (PDR), the mean number of
      adenomas per colonoscopy (MNA) and mean number of polyps (MNP) and the proportion
      of adenomas among polyps (PAP). RESULTS: Correlations were good between the ADR
      and PDR (Pearson coefficient r = 0.88 [95% CI, 0.78-0.94]) and between MNA and
      MNP (r = 0.89 [95% CI, 0.79-0.94]) (P < .0001 for both). Gastroenterologists were
      classified as higher or lower detectors in comparison with the lower limit of the
      95% confidence interval of the median value for each indicator. The MNP (MNA)
      provided better discrimination than the PDR (ADR). Concordance between
      classifications of gastroenterologists according to their MNA and MNP was
      excellent (kappa = 0.89). PAP varied dramatically from 38% to 95% between
      gastroenterologists and was very poorly correlated with the ADR (r = -0.27 [95%
      CI, -0.54 to 0.07; P = .11]) and the MNA (r = 0.03 [95% CI, -0.29 to 0.36; P =
      .88]). LIMITATIONS: Some factors influencing the neoplasia yield were not taken
      into account. CONCLUSIONS: The MNP could replace the ADR for the assessment of
      adenoma detection in routine practice. A separate indicator, PAP, would be
      necessary to assess adenoma discrimination ability.

PMID- 21958900
TI  - Effect of a difficult calving on the vigour of the calf, the onset of maternal
      behaviour, and some behavioural indicators of pain in the dam.
AB  - The neonate's development and survival is dependent upon being vigorous at birth
      and receiving appropriate maternal care. However, difficulty at delivery can
      result in less vigorous offspring and maternal care can be altered, probably as a
      consequence of exhaustion, pain and human intervention. The first 3h after
      expulsion of the calf were observed continuously from videos following twelve
      natural calvings and sixteen calvings assisted by farm staff (including four
      malpresentations) from Holstein cows. Calvings were balanced within groups for
      parity of the dam, genetic group, sex and birth weight of the calf, calving pen
      and calving season. Assisted calves were less vigorous with higher latencies to
      attempt to stand, achieve standing, walk and reach the udder than unassisted
      calves (P<0.05). Furthermore, assisted calves also tended to be less likely to
      stand and walk within the first 3h after birth (P<0.1), spent more time lying on
      their flank (P=0.019) and had more frequent bouts of this behaviour (P=0.033).
      Assisted dams did not take longer to lick the calf and performed as much licking
      as unassisted dams (P>0.05), indicating no delayed onset or impaired expression
      of maternal behaviour in dams given assistance at delivery. Study of potential
      pain-related behaviours revealed that assisted dams spent less time self-grooming
      (P=0.033) than dams delivering naturally, which could suggest greater pain.
      However, there were no significant differences in any of the other pain-related
      behaviours. Our results suggest that, although maternal behaviour was unaffected
      by a difficult delivery, dairy calves born following difficult calvings have
      lower vigour in the first 3h after birth than unassisted calves. This might have
      longer-term effects on the health and survival of the calves.

PMID- 21958901
TI  - Factors affecting dystocia and offspring vigour in different sheep genotypes.
AB  - Birth difficulty and poor lamb vigour are significant causes of perinatal lamb
      mortality. In this study we investigated whether sheep breeds differing in
      appearance, muscularity and selection history also had differences in dystocia
      and lamb vigour, and considered some of the factors that may contribute to the
      variation in these traits. Data were collected at birth from a total of 3252
      lambs of two terminal sire breeds selected for lean growth (Suffolk [S], n=500
      and Texel [T], n=1207), from a Hill breed (Scottish Blackface [B], n=610), which
      has been mainly selected for hardiness, and a crossbred (Mule*T [M], n=935)
      representing a maternal line. For each lamb the degree of assistance at delivery,
      lamb presentation, amount of assistance to achieve successful sucking, sex,
      litter size and birth weight were recorded. T lambs required the most, and B and
      M lambs the least assistance at birth, S lambs were intermediate (% lambs
      assisted: T=55.7, S=30.7, B=22.7, M=24.9, P<0.001). T and S lambs were equally
      likely to be malpresented at birth (29% of births) and more likely to be
      malpresented than B or M lambs (20%; P<0.001). In T and S breeds lambs requiring
      veterinary assistance at delivery were mainly heavy and singleton lambs, whereas
      in B and M breeds these were exclusively low birth weight lambs in multiple
      litters. Although heavier lambs needed greater birth assistance, T lambs were
      lighter than S and M lambs, but heavier than B lambs (birth weight (kg): S=4.66,
      M=4.56, T=4.32, B=3.67, P<0.001). S lambs were more likely to require assistance
      with sucking than other breeds, and T lambs also required more assistance than B
      or M lambs (% lambs assisted to suck: S=56.0, T=31.6, M=19.8, B=18.4, P<0.001).
      Heavier lambs were more likely to suck unaided than lighter lambs (P<0.001). The
      data suggest that the two terminal sire breeds, selected narrowly for greater
      productivity (muscle growth and conformation), are more likely to experience
      birth difficulty and poorer lamb vigour than the breed selected for hardiness, or
      the cross breed. Whether these effects arise as a consequence of genetic
      selection (e.g. for specific lamb conformation), or as a result of management
      practices to achieve selection goals (e.g. increased intervention at lambing) is
      unknown. Specific actions to improve birth difficulty and lamb vigour, such as
      including these traits in the selection index, would be beneficial in improving
      the welfare of ewes and lambs of the terminal sire breeds.

PMID- 21958902
TI  - Etiology and treatment of pediatric sixth nerve palsy.

PMID- 21958903
TI  - Validity and ease of use of a computerized Hess chart.
AB  - PURPOSE: To investigate agreement between computerized and conventional methods
      for obtaining Hess charts and to compare relative ease of use of both methods.
      METHODS: Hess charts of 65 patients were obtained by the use of the computerized
      Assaf Ocular Motility Analyzer (OMA) and the conventional Lees screen method. The
      Hess charts produced by each method were compared with a previously described
      scoring system. Patients compared the ease of testing by using a 5-point Likert
      scale. RESULTS: For horizontal deviations of the right eye, the OMA provided a
      significantly larger (P = 0.0001) deviation (301 degrees  +/- 267 degrees ) than
      the Lees screen (204 degrees  +/- 306 degrees ). The Lees screen gave a
      significantly larger score for vertical deviations of the left eye (117 degrees 
      +/- 158 degrees  vs 96 degrees  +/- 129 degrees ; P = 0.003). Vertical deviations
      of the right eye and horizontal deviations of the left eye did not differ
      significantly between tests. Patients required the same amount of time to
      complete both tests, but the OMA was slightly easier to perform than the Lees
      screen (Likert score, 1.2 +/- 0.5 vs 1.3 +/- 0.4; P = 0.046). CONCLUSIONS: The
      scores measured were larger with OMA in the horizontal and smaller in the
      vertical direction than with the Lees screen in some directions. Although the OMA
      did not save time, patients found it easier to perform than the Lees screen. The
      OMA may be considered a useful alternative to the Lees screen.

PMID- 21958904
TI  - Pediatric optic neuritis and multiple sclerosis: who is at risk for progression?

PMID- 21958905
TI  - Pituitary adenoma causing visual disturbances in a 6-year-old girl.
AB  - Pituitary adenomas rarely occur in young children, typically present with
      systemic symptoms, and rarely undergo malignant transformation. We report a 4
      year-old girl who presented with visual disturbances initially diagnosed and
      treated as amblyopia. She subsequently developed headaches and a gait disturbance
      and was discovered to have a large, suprasellar, nonsecreting pituitary adenoma.
      The tumor was resected, but 22 months later she developed recurrence with
      malignant transformation.

PMID- 21958906
TI  - Treatment of symptomatic convergence insufficiency with a home-based computer
      orthoptic exercise program.

PMID- 21958907
TI  - Secondary in-the-bag intraocular lens implantation in children who have been
      aphakic since early infancy.

PMID- 21958908
TI  - Assessing food web dynamics and relative importance of organic matter sources for
      fish species in two Portuguese estuaries: a stable isotope approach.
AB  - Stable carbon and nitrogen isotopes (delta13C, delta15N) were used to analyse
      food web dynamics of two of the main estuaries of the Portuguese coast: Tejo and
      Mira. The ultimate sources of organic matter supporting production of some of the
      most abundant and commercially important fish species were determined; and
      seasonal, inter- and intra- estuarine differences in the trophic relations among
      producers and consumers were identified. Stable isotope analysis was performed in
      different producers, primary consumers (main prey items for fish) and fish
      species (Solea solea, Solea senegalensis, Pomatoschistus microps, Dicentrarchus
      labrax, Liza ramada, Diplodus vulgaris and Atherina presbyter) of two areas in
      each estuary, in July and October 2009. Model calculations showed that the main
      prey for the fish species in the Tejo estuary used mostly salt marsh-derived
      organic matter as nutritional sources, with no marked differences between the
      sampled months. Trophic levels of fish species from the same estuary differed at
      multiple scales: inter-species, seasonally and spatially (both between and within
      estuaries). Significant differences in isotopic composition of fish species were
      more pronounced spatially (between the two sampled areas in the estuary) than
      seasonally (between sampled months). Trophic relationships in both estuaries
      demonstrated that organic matter is transferred to higher trophic positions
      mainly through benthic pathways. This shows the flexibility of these species to
      share resources and to exploit temporary peaks in prey populations. The present
      results showed that extensive disturbance in intertidal habitats from both
      estuaries may potentially change the balance of organic matter in the base of
      these complex food webs.

PMID- 21958909
TI  - Mononucleated and binucleated cardiomyocytes in left atrium and pulmonary vein
      have different electrical activity and calcium dynamics.
AB  - Cardiomyocytes consist of single- and bi-nucleus myocytes. However, the
      electrophysiological characteristics of mononucleated and binucleated myocytes
      have never been elucidated. Left atrium (LA) and pulmonary veins (PVs) are
      important substrate and initiators of atrial fibrillation. The purposes of this
      study were to evaluate the electrical properties and calcium homeostasis in
      mononucleated and binucleated cardiomyocytes in the LA and PVs. A whole-cell
      clamp, fluo-4 fluorescence, and immunocytostaining were used to investigated
      mononucleated and binucleated cardiomyocytes in the LA and PVs. Both
      mononucleated PV and LA cardiomyocytes had more positive resting membrane
      potential than respective PV and LA binucleated cardiomyocytes. Additionally,
      mononucleated PV cardiomyocytes (n = 36) had faster beating rates (2.1 +/- 0.2 Hz
      versus 1.0 +/- 0.2 Hz, P < 0.05) than binucleated (n = 10) PV cardiomyocytes. The
      PV (n = 18) and LA (n = 15) mononucleated cardiomyocytes had larger [Ca2+](i)
      transients (F/F0 1.64 +/- 0.09 versus 1.20 +/- 0.03 IU, P < 0.05; 1.52 +/- 0.06
      versus 1.19 +/- 0.05 IU, P < 0.05) than the binucleated PV (n = 10) and LA (n =
      10) cardiomyocytes. The immunostaining showed that mononucleated cardiomyocytes
      had lower Kir 2.3 and higher ryanodine receptor densities than did binucleated
      cardiomyocytes both in the PV and LA. In conclusions, mononucleated PV and LA
      cardiomyocytes contain distinctive electrophysiological characteristics with a
      higher arrhythmogenic activity, which indicates that cell nucleus number may
      potentially determine the electrical activity and calcium handling in
      cardiomyocytes.

PMID- 21958910
TI  - Reviews on sun exposure and artificial light and melanoma.
AB  - Melanoma is the most common form of cancer among young adults aged 25-29 years
      and the second most common cancer in those aged 15-29 years. We reviewed all the
      evidence regarding risk factors for melanoma, looking in particular at childhood
      exposure to ultraviolet radiation (UV). UV radiation is clearly the predominant
      environmental and thus potentially modifiable risk factor for melanoma. All
      activities related to tan-seeking behaviour and history of sunburns were shown to
      be significantly associated to melanoma. Host factors, such as pigmentary
      characteristics, and genetic predisposition plays also an important role. UV
      exposure is not only due to the sun but also to indoor tanning devices that have
      been shown to lead to an elevated risk of melanoma. The strongest evidence for a
      link between artificial UV and melanoma is found among individuals who had their
      first exposure to indoor tanning before the age of 30: they have a 75% increase
      risk of developing melanoma than individuals who had no exposure to indoor
      tanning. Prevention is very important, especially for children and young adults,
      as childhood and adolescence are critical periods in the development of later
      melanoma. Indoor tanning is a widespread practice in most developed countries,
      particularly in Northern Europe and the USA. In the recent decades more and more
      people, especially teenagers and women, are exposed to substantially high radiant
      exposures of UV through artificial sources and these trends raised a considerable
      concern. In fact the International Agency for Research on Cancer concluded that
      the association between skin cancer and exposure to solar radiation and the use
      of UV-emitting tanning devices are causal. Interesting analyses carried out in
      Iceland showed that when interventions to discourage sunbed use were introduced
      the incidence of melanoma among women decreased. All this evidence encouraged
      many countries to introduce regulations on sunbed use to avoid exposure before
      the age of 18.

PMID- 21958911
TI  - Mobile phones, radiofrequency fields, and health effects in children-
      epidemiological studies.
AB  - In 2004, when WHO organized a workshop on children's sensitivity to
      electromagnetic fields, very few studies on radiofrequency fields were available.
      With the recent increase in mobile phone use among children and adolescents, WHO
      has identified studies on health effects in this age-group as a high priority
      research area. There are no empirical data supporting the notion that children
      and adolescents are more susceptible to RF exposure, but the number of studies is
      still relatively small. There are a few cross-sectional studies on well-being,
      cognitive effects and behavioral problems, and some cohort studies, mainly of
      maternal use of mobile phones during pregnancy. Cancer outcomes have been studied
      in relation to environmental RF exposure, e.g. from transmitters, and only one
      study on mobile phone use in children and adolescents and brain tumor risk has
      been published. Several methodological limitations need to be taken into
      consideration when interpreting the findings of the epidemiological studies. The
      cross-sectional design does not allow determination of the temporal sequence of
      exposure and outcome, and for several outcomes there is a large potential for
      reversed causality, i.e. that the outcome causes an increased RF exposure rather
      than the opposite. Biases such as recall errors in self-reported mobile phone
      use, lack of confounding control, e.g. of other aspects of mobile phone use than
      RF fields, trained behaviors, and pubertal development, makes causal
      interpretations impossible. Future studies need to include prospectively
      collected exposure information, incident outcomes, and proper confounding
      control. Monitoring of brain tumor incidence trends is strongly recommended.

PMID- 21958912
TI  - Childhood leukemia--risk factors and the need for an interdisciplinary research
      agenda.
AB  - The International Agency for Research on Cancer (IARC) has classified high as
      well as low-frequency fields as "possibly carcinogenic to humans" (Group 2B). For
      high frequency fields the recent assessment is based mainly on weak positive
      associations described in some epidemiological studies between glioma and
      acoustic neuroma and the use of mobile and other wireless phones. Also for
      lowfrequency fields the evidence is based on epidemiological findings revealing a
      statistic association between childhood leukemia (CL) and low-level magnetic
      fields. The basic findings are already 10 years old. They have since been
      supported by further epidemiological studies. However, the knowledge on the
      main/crucial question of causality has not improved. This fact and in addition
      the small, but statistically significant increased incidence of CL in the
      surrounding of German nuclear power plants have motivated the German Office for
      Radiation Protection (BfS) to work toward a better understanding of the main
      causes of CL. A long-term strategic research agenda has been developed which
      builds on an interdisciplinary, international network and aims at clarifying the
      aetiology of childhood acute lymphoblastic leukemia.

PMID- 21958913
TI  - Retrotransposition of R2 elements in somatic nuclei during the early development
      of Drosophila.
AB  - BACKGROUND: R2 retrotransposable elements exclusively insert in the 28S rRNA
      genes of their host. Their RNA transcripts are produced by self-processing from a
      28S R2 cotranscript. Because full-length R2 transcripts are found in most tissues
      of R2-active animals, we tested whether new R2 insertions occurred in somatic
      tissues even though such events would be an evolutionary dead end. FINDINGS: PCR
      assays were used to identify somatic R2 insertions in isolated adult tissues and
      larval imaginal discs of Drosophila simulans. R2 somatic mosaics were detected
      encompassing cells from individual tissues as well as tissues from multiple body
      segments. The somatic insertions had 5' junction sequences characteristic of
      germline insertions suggesting they represented authentic retrotransposition
      events. CONCLUSIONS: Body segments are specified early in Drosophila development,
      thus the detection of the same somatic insertion in cells from multiple tissues
      suggested that the R2 retrotransposition events had occurred before the
      blastoderm stage of Drosophila development. R2 activity at this stage, when
      embryonic nuclei are rapidly dividing in a common cytoplasm, suggests that some
      retrotransposition events appearing as germline events may correspond to germline
      mosaicism.

PMID- 21958914
TI  - Long-term myocardial recovery after mitral valve replacement in noncompaction
      cardiomyopathy.
AB  - Isolated noncompaction of the left ventricle is a congenital cardiomyopathy,
      which has been described recently, with literature limited to case reports and
      case series. Even though various complications have been reported with
      noncompaction cardiomyopathy, among them severe mitral regurgitation has been
      reported recently in a few cases. There is no great evidence in the literature
      about its management, apart from some cases of mitral valve repair and
      replacement in young patients. We are reporting a case of an elderly lady with
      isolated left ventricular noncompaction cardiomyopathy associated with severe
      mitral regurgitation treated with mitral valve replacement with one and half year
      of follow up demonstrating significant myocardial recovery.

PMID- 21958915
TI  - Assisted reproductive travel: UK patient trajectories.
AB  - Media reporting of 'fertility tourism' tends to portray those who travel as a
      cohesive group, marked by their desperation and/or selfishness and propensity
      towards morally questionable behaviour. However, to date little has been known
      about the profile of those leaving the UK for treatment. This paper discusses the
      first UK-based study of patient assisted reproduction travel that was designed to
      explore individual travel trajectories. It is argued that existing ways of
      conceptualizing cross-border reproductive care as 'fertility or reproductive
      tourism' are in danger of essentializing what the data suggest are diverse,
      complex and often ambiguous motivations for reproductive travel. The concept of
      seriality is used to suggest that, whilst 'reproductive tourists' share some
      characteristics, they also differ in significant ways. This paper argues that,
      through an examination of the personal landscapes of fertility travel, the
      diverse processes involved in reproductive travel can be better understood and
      policymakers can be assisted to avoid what might be regarded as simplistic
      responses to cross-border reproductive care.

PMID- 21958916
TI  - Transnational commercial surrogacy in India: gifts for global sisters?
AB  - In this ethnography of transnational commercial surrogacy in a small clinic in
      India, the narratives of two sets of women involved in this new form of
      reproductive travel - the transnational clients and the surrogates themselves -
      are evaluated. How do these women negotiate the culturally anomalous nature of
      transnational surrogacy within the unusual setting of India? It is demonstrated
      that while both sets of women downplay the economic aspect of surrogacy by
      drawing on predictable cultural tools like 'gift', 'sisterhood' and 'mission',
      they use these tools in completely unexpected ways. Previous ethnographies of
      surrogacy in other parts of the world have revealed that women involved in
      surrogacy use these narratives to downplay the contractual nature of their
      relationship with each other. Ironically, when used in the context of
      transnational surrogacy in India, these narratives further highlight and often
      reify the inequalities based on class, race and nationality between the clients
      and suppliers of reproductive tourism in India.

PMID- 21958917
TI  - Advances in outcomes measurement in rehabilitation medicine: current initiatives
      from the National Institutes of Health and the National Institute on Disability
      and Rehabilitation Research.
AB  - The articles in this supplement present recent advances in the measurement of
      patient-reported health-related quality-of-life (HRQOL) outcomes. Specifically,
      these articles highlight the combined efforts of the National Institutes of
      Health, National Institute for Neurological Disorders and Stroke, National Center
      on Medical Rehabilitation Research, National Institute on Disability and
      Rehabilitation Research, and Department of Veterans Affairs Rehabilitation
      Research and Development Service to improve HRQOL measurement. In addition, this
      supplement is intended to provide rehabilitation professionals with information
      about these efforts and the implications that these advances in outcomes
      measurement have for rehabilitation medicine and clinical practice. These new
      measurement scales use state-of-the-art method techniques, including item
      response theory and computerized adaptive testing. In addition, scale development
      involves both qualitative and quantitative methods, as well as the administration
      of items to hundreds or even thousands of research participants. The scales
      deliberately have been built with overlap of items between scales so that
      linkages and equivalency scores can be computed. Ultimately, these scales should
      facilitate direct comparison of outcomes instruments across studies and will
      serve as standard data elements across research trials without compromising the
      specificity of disease- or condition-targeted measures. This supplement includes
      the initial publications for many of these new measurement initiatives, each of
      which provides researchers and clinicians with better tools for evaluation of the
      efficacy of their interventions.

PMID- 21958918
TI  - The PROMIS initiative: involvement of rehabilitation stakeholders in development
      and examples of applications in rehabilitation research.
AB  - To fully capture the impact of a disease or condition on the lives of
      individuals, patient-reported outcomes are considered a necessary component of
      health measurement in rehabilitation. This article provides an overview of the
      involvement of rehabilitation stakeholders in the development of sound
      measurement tools for the Patient-Reported Outcomes Measurement Information
      System (PROMIS), a National Institutes of Health-funded initiative. PROMIS is a
      multisite study that included many different populations. We focus on the
      involvement of people with several chronic conditions, including multiple
      sclerosis, spinal cord injury, and arthritis, in the development of PROMIS
      measures. We describe both qualitative and quantitative methods used, including
      expert panels, focus groups, cognitive interviews, and item response theory
      modeling, which resulted in enhanced utility of PROMIS measures in
      rehabilitation. Measures include a set of global health items and 12 item banks
      representing 6 domains. Scores are reported in the T score metric (mean +/- SD,
      50 +/- 10) and centered on mean values from the U.S. general population. The
      PROMIS item banks measure quality of life and symptoms of people with chronic
      conditions and have the potential to enhance research and clinical practice by
      facilitating comparisons of scores across domains and populations.

PMID- 21958919
TI  - How item banks and their application can influence measurement practice in
      rehabilitation medicine: a PROMIS fatigue item bank example.
AB  - OBJECTIVE: To illustrate how measurement practices can be advanced by using as an
      example the fatigue item bank (FIB) and its applications (short forms and
      computerized adaptive testing [CAT]) that were developed through the National
      Institutes of Health Patient Reported Outcomes Measurement Information System
      (PROMIS) Cooperative Group. DESIGN: Psychometric analysis of data collected by an
      Internet survey company using item response theory-related techniques. SETTING: A
      U.S. general population representative sample collected through the Internet.
      PARTICIPANTS: Respondents used for dimensionality evaluation of the PROMIS FIB
      (N=603) and item calibrations (N=14,931). INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Fatigue items (112) developed by the PROMIS fatigue domain
      working group, 13-item Functional Assessment of Chronic Illness Therapy-Fatigue,
      and 4-item Medical Outcomes Study 36-Item Short Form Health Survey Vitality
      scale. RESULTS: The PROMIS FIB version 1, which consists of 95 items, showed
      acceptable psychometric properties. CAT showed consistently better precision than
      short forms. However, all 3 short forms showed good precision for most
      participants in that more than 95% of the sample could be measured precisely with
      reliability greater than 0.9. CONCLUSIONS: Measurement practice can be advanced
      by using a psychometrically sound measurement tool and its applications. This
      example shows that CAT and short forms derived from the PROMIS FIB can reliably
      estimate fatigue reported by the U.S. general population. Evaluation in clinical
      populations is warranted before the item bank can be used for clinical trials.

PMID- 21958920
TI  - The neurology quality-of-life measurement initiative.
AB  - OBJECTIVE: To describe the development and calibration of the banks and scales of
      the Quality of Life in Neurological Disorders (Neuro-QOL) project, commissioned
      by the National Institute of Neurological Disorders and Stroke to develop a
      bilingual (English/Spanish), clinically relevant, and psychometrically robust
      health-related quality-of-life (HRQOL) assessment tool. DESIGN: Classic and
      modern test construction methods were used, including input from essential
      stakeholder groups. SETTING: An online patient panel testing service and 11
      academic medical centers and clinics from across the United States and Puerto
      Rico that treat major neurologic disorders. PARTICIPANTS: Adult and pediatric
      patients representing different neurologic disorders specified in this study,
      proxy respondents for select conditions (stroke, pediatric conditions), and
      English- and Spanish-speaking participants from the general population.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Multiple generic and
      condition-specific measures used to provide construct validity evidence for the
      new Neuro-QOL tool. RESULTS: Neuro-QOL has developed 14 generic item banks and 8
      targeted scales to assess HRQOL in 5 adult (stroke, multiple sclerosis,
      Parkinson's disease, epilepsy, amyotrophic lateral sclerosis) and 2 pediatric
      conditions (epilepsy, muscular dystrophies). CONCLUSIONS: The Neuro-QOL system
      will continue to evolve, with validation efforts in clinical populations and new
      bank development in health domains not presently included. The potential for
      Neuro-QOL measures in rehabilitation research and clinical settings is discussed.

PMID- 21958921
TI  - Linking the activity measure for post acute care and the quality of life outcomes
      in neurological disorders.
AB  - OBJECTIVE: To use item response theory (IRT) methods to link physical functioning
      items in the Activity Measure for Post Acute Care (AM-PAC) and the Quality of
      Life Outcomes in Neurological Disorders (Neuro-QOL). DESIGN: Secondary data
      analysis of the physical functioning items of AM-PAC and Neuro-QOL. We used a
      nonequivalent group design with 36 core items common to both instruments and a
      test characteristic curve transformation method for linking AM-PAC and Neuro-QOL
      scores. Linking was conducted so that both raw and scaled AM-PAC and Neuro-QOL
      scores (mean +/- SD converted-logit scores, 50 +/- 10) could be compared.
      SETTING: AM-PAC items were administered to rehabilitation patients in post-acute
      care (PAC) settings. Neuro-QOL items were administered to a community sample of
      adults through the Internet. PARTICIPANTS: PAC patients (N=1041) for the AM-PAC
      sample and community-dwelling adults (N=549) for the Neuro-QOL sample.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Mobility (N=25) and
      activity of daily living (ADL) items (N=11) common to both instruments were
      included in analysis. RESULTS: Neuro-QOL items were linked to the AM-PAC scale by
      using the generalized partial credit model. Mobility and ADL subscale scores from
      the 2 instruments were calibrated to the AM-PAC metric. CONCLUSIONS: An IRT-based
      linking method placed AM-PAC and Neuro-QOL mobility and ADL scores on a common
      metric. This linking allowed estimation of AM-PAC mobility and ADL subscale
      scores based on Neuro-QOL mobility and ADL subscale scores and vice versa. The
      accuracy of these results should be validated in a future sample in which
      participants respond to both instruments.

PMID- 21958923
TI  - Traumatic brain injury patient-reported outcome measure: identification of health
      related quality-of-life issues relevant to individuals with traumatic brain
      injury.
AB  - This 2-part qualitative study explored health-related quality of life (HRQOL) in
      individuals with traumatic brain injury (TBI). A community-based participatory
      action research design was used, which emphasizes collaboration between
      researchers and individuals with disabilities to ensure that results are relevant
      for individuals with TBI. In study 1, community members (N=20) with TBI served as
      "experts" during 1-on-1 semistructured interviews, reviewing current HRQOL items
      and identifying HRQOL issues commonly experienced by individuals with TBI. Each
      participant identified at least 31 issues, with most generating more than 90
      responses, highlighting the multifaceted nature of HRQOL in TBI. Study 2
      consisted of 7 patient/consumer groups (33 individuals with TBI), 4 caregiver
      groups (17 caregivers), and 2 provider groups (15 providers). Qualitative
      analysis of patient focus groups indicated that 48% of focus group comments were
      related to emotional issues; 23%, to social functioning; 14%, to physical
      functioning; 11%, to cognition; and 7%, to personality changes (caregiver and
      provider focus group analysis indicated identical patterns of findings). In
      addition, both studies evaluated the applicability in TBI of generic items
      developed by the Patient-Reported Outcomes Measurement Information System and the
      Neurology Quality of Life Measurement initiative. Findings suggest that although
      there is some overlap between current generic measures of HRQOL and concepts
      reported by individuals with TBI, these generic measures do not capture the full
      complexity of HRQOL in TBI. TBI-targeted item banks are needed to ensure
      sensitive assessment of HRQOL in TBI.

PMID- 21958922
TI  - Developing a contemporary patient-reported outcomes measure for spinal cord
      injury.
AB  - OBJECTIVE: To develop a spinal cord injury (SCI)-specific patient-reported
      outcome (PRO) measure of health-related quality of life (QOL) covering multiple
      domains of functioning, including physical, emotional, and social health. DESIGN:
      Focus groups. SETTING: Four SCI Model Systems rehabilitation hospitals.
      PARTICIPANTS: Individuals with SCI (n=65) and clinicians (n=42). INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURE: Spinal Cord Injury Quality of Life
      Measurement System (SCI-QOL). RESULTS: Qualitative analysis yielded 3 domains of
      primary importance: physical-medical health, emotional health, and social
      participation. Results were used to guide domain and item decisions in the
      development of the SCI-QOL PRO measurement system. Qualitative data were used to
      develop item pools with item content specific to individuals with SCI across a
      wide spectrum of functioning. When possible, items from other major measurement
      initiatives were included verbatim in the item pools to link the measurement
      systems and facilitate cross-study and cross-population comparisons. CONCLUSIONS:
      Issues that affect individuals' QOL after SCI are varied and several issues are
      unique to individuals who have had a traumatic injury. From these qualitative
      data, 3 major domains and 18 subdomains of functioning were identified. Item
      pools were developed in each of these 18 areas to measure functioning related to
      physical-medical issues, emotional status, and social participation.

PMID- 21958925
TI  - Future of outcomes measurement: impact on research in medical rehabilitation and
      neurologic populations.
AB  - The National Institutes of Health (NIH) has embraced the investigation and
      development of health-related patient-reported outcomes (PROs) for their
      potential use in clinical trials, as well as in examining health care
      reimbursements and regulatory affairs. The NIH has 3 major programs to address
      this topic: the Patient-Reported Outcomes Measurement Information System
      (PROMIS), NIH Toolbox for Assessment of Neurological and Behavioral Function, and
      Quality of Life in Neurological Disorders (Neuro-QOL), a health-related quality
      of-life assessment tool for adults and children with neurologic disorders. These
      initiatives are focused on developing, validating, and measuring aspects of
      health by using assessment tools that bridge disease type. Given that
      rehabilitation takes place across a variety of environments with differing levels
      of specialized equipment and skilled personnel, PROs may provide consistent
      measures over time and therefore are anticipated to have substantial impacts on
      the medical rehabilitation community. Despite their advantages, the widespread
      use of PROs in rehabilitation faces significant and diverse challenges. This
      article describes the background behind the NIH PRO initiatives and illustrates
      both potential benefits and challenges to PRO use in the medical rehabilitation
      setting.

PMID- 21958926
TI  - Heating of gases during neonatal resuscitation: a bench study.
AB  - AIM: Standard practice within the neonatal unit is to use heated humidified gas
      as it decreases respiratory complications in neonates requiring respiratory
      support. Using cold unhumidified gases during resuscitation could potentially
      cool the baby as well as exacerbate potential lung injury. We aimed to study the
      temperature and humidity aspects of using heated, humidified gas for neonatal
      resuscitation. METHODS: A heated patient circuit was connected to a T-piece
      resuscitator via a humidifier. An oxygen flowmeter was set at 10 L/min.
      Temperature recordings at the humidifier chamber (T1), distal temperature probe
      (T2) and T-piece (T3) were taken over 20 min at 30s intervals. A humidity sensor
      was placed at T3. RESULTS: Target temperatures were not reached. Time to 36
      degrees C (mean (sd)): T1 11.1 min (1.71); T3 11.6 min (1.77). T2 took 13.6 min
      (1.07) to reach 39 degrees C. T1 and T3 were within +/-1 degrees C at 5.1 min
      (0.6). A biphasic relationship demonstrated the time lag between the temperatures
      of the heated patient circuit and the humidifier chamber. T3 strongly correlated
      to T1 when T1 is >=28 degrees C (r(2)=0.85). Humidity was difficult to measure
      and results were inferred from temperature recordings. CONCLUSION: This in vitro
      test showed that heated, humidified gas is possible during neonatal
      resuscitation. Adequate time must be allowed for the humidifier chamber to warm
      to near optimal temperature. The patient circuit is initially heated faster than
      the humidifier chamber. The displayed T1 temperature correlates to the
      temperature at T3 at >=28 degrees C.

PMID- 21958927
TI  - Comparison of air-Q((r)) and Soft Seal((r)) laryngeal mask for airway management
      by novice doctors during infant chest compression: a manikin study.
AB  - BACKGROUND: Recent resuscitation guidelines for infant cardiopulmonary
      resuscitation (CPR) emphasise that rescuers should minimise the interruption of
      chest compressions. To that end, supraglottic devices such as laryngeal mask
      airways (LMAs) are suggested as a backup for airway management during infant CPR.
      We therefore compared the utility of the air-Q((r)) LMA (air-Q) with that of the
      Soft Seal((r)) LMA (Soft Seal) for infant CPR in an infant manikin. METHODS:
      Twenty-four novice doctors in the anaesthesia department performed insertion and
      ventilation with air-Q and Soft Seal on an infant manikin with or without chest
      compression. RESULTS: Two doctors failed to insert the Soft Seal without chest
      compression, while nine failed during chest compression (P<0.05). However, only
      one doctor failed to insert the air-Q without chest compression, and two doctors
      failed during chest compression. Insertion time was not significantly increased
      with chest compression using either device. Insertion time during chest
      compression was significantly shorter for the air-Q than for the Soft Seal
      (P<0.05). The visual analogue scale (VAS) was used to evaluate difficulty of use
      (0mm (extremely easy) to 100mm (extremely difficult)). VAS scores did not change
      significantly by the addition of chest compression with either device; however,
      VAS scores during chest compression were significantly higher with Soft Seal than
      with the air-Q device. CONCLUSION: We conclude that novice doctors find the air-Q
      easier to use than Soft Seal for emergency airway management during chest
      compression in infants, in an infant manikin.

PMID- 21958928
TI  - Effect of a reminder video using a mobile phone on the retention of CPR and AED
      skills in lay responders.
AB  - BACKGROUND: Skills related to cardiopulmonary resuscitation (CPR) and automated
      external defibrillator (AED) use by lay responders decay rapidly after training,
      and efforts are required to maintain competence among trainees. We examined
      whether repeated viewing of a reminder video on a mobile phone would be an
      effective means of maintaining CPR and AED skills in lay responders. METHODS: In
      a single-blind case-control study, 75 male students received training in CPR and
      AED use. They were allocated either to the control or to the video-reminded
      group, who received a memory card containing a video clip about CPR and AED use
      for their mobile phone, which they were repeatedly encouraged to watch by SMS
      text message. CPR and AED skills were assessed in scenario format by examiners
      immediately and 3 months after initial training. RESULTS: Three months after
      initial training, the video-reminded group showed more accurate airway opening
      (P<0.001), breathing check (P<0.001), first rescue breathing (P=0.004), hand
      positioning (P=0.004), AED electrode positioning (P<0.001), pre-shock safety
      check (P<0.001), defibrillation within 90s (P=0.010), and resuming CPR after
      defibrillation (P<0.001) than controls. They also showed significantly higher
      self-assessed CPR confidence scores and increased willingness to perform
      bystander CPR in cardiac arrest than the controls at 3 months (P<0.001, P=0.024,
      respectively). CONCLUSION: Repeated viewing of a reminder video clip on a mobile
      phone increases retention of CPR and AED skills in lay responders.

PMID- 21958929
TI  - Comparison of manually triggered ventilation and bag-valve-mask ventilation
      during cardiopulmonary resuscitation in a manikin model.
AB  - BACKGROUND: To compare a novel, pressure-limited, flow adaptive ventilator that
      enables manual triggering of ventilations (MEDUMAT Easy CPR, Weinmann, Germany)
      with a bag-valve-mask (BVM) device during simulated cardiac arrest. METHODS:
      Overall 74 third-year medical students received brief video instructions (BVM:
      57s, ventilator: 126s), standardised theoretical instructions and practical
      training for both devices. Four days later, the students were randomised into 37
      two-rescuer teams and were asked to perform 8min of cardiopulmonary resuscitation
      (CPR) on a manikin using either the ventilator or the BVM (randomisation list).
      Applied tidal volumes (V(T)), inspiratory times and hands-off times were
      recorded. Maximum airway pressures (P(max)) were measured with a sensor connected
      to the artificial lung. Questionnaires concerning levels of fatigue, stress and
      handling were evaluated. V(T), pressures and hands-off times were compared using
      t-tests, questionnaire data were analysed using the Wilcoxon test. RESULTS: BVM
      vs. ventilator (mean+/-SD): the mean V(T) (408+/-164ml vs. 315+/-165ml, p=0.10)
      and the maximum V(T) did not differ, but the number of recorded V(T)<200ml
      differed (8.1+/-11.3 vs. 17.0+/-14.4 ventilations, p=0.04). P(max) did not
      differ, but inspiratory times (0.80+/-0.23s vs. 1.39+/-0.31s, p<0.001) and total
      hands-off times (133.5+/-17.8s vs. 162.0+/-11.1s, p<0.001) did. The estimated
      levels of fatigue and stress were comparable; however, the BVM was rated to be
      easier to use (p=0.03). CONCLUSION: For the user group investigated here, this
      ventilator exhibits no advantages in the setting of simulated CPR and carries a
      risk of prolonged no-flow time.

PMID- 21958930
TI  - Quality controlled manual chest compressions and cerebral oxygenation during in
      hospital cardiac arrest.
AB  - AIM: The quality of cardiopulmonary resuscitation (CPR) is associated with the
      rate of return of spontaneous circulation (ROSC) during human cardiac arrest.
      Current advances in defibrillator technology enable measurement of CPR quality
      during resuscitation, but it is not known whether this is directly reflected in
      cerebral oxygenation. In this descriptive study we aimed to evaluate whether the
      quality of feedback-monitored CPR during in-hospital cardiac arrest is reflected
      in near infrared frontal cerebral spectroscopy (NIRS). METHODS: Nine patients
      suffering an in-hospital cardiac arrest in a university hospital were included.
      All patients underwent quality-controlled CPR performed by a dedicated medical
      emergency team using a Philips HeartStart MRx defibrillator (Philips, Eindhoven,
      Netherlands) with a CPR quality (Q-CPR, Laerdal Medical, Stavanger, Norway)
      analysis feature. Simultaneously, bilateral frontal cerebral oximetry was
      measured using INVOS 5100c (Somanetics, Troy, MI, USA) NIRS. RESULTS: During
      quality controlled resuscitation, regional cerebral oxygenation (rSO(2)) as
      measured with NIRS was low but it improved during CPR (p=0.043) and 8 min after
      ROSC (p=0.022). After the onset of NIRS recording, there were four episodes
      exceeding 30s, during which the quality of CPR was substandard. When CPR
      technique was corrected and maintained for 2 min, a minor non-significant
      increase in rSO(2) was observed in two cases. CONCLUSIONS: High quality CPR was
      not significantly reflected in cerebral oxygenation as quantified using NIRS.
      Even after ROSC and subsequent significant increase in cerebral oxygenation,
      rSO(2) readings were below previously suggested threshold of cerebral ischaemia.
      Improving CPR technique after an episode of low quality CPR did not significantly
      increase rSO(2).

PMID- 21958931
TI  - Out-of-hospital cardiac arrest in patients treated with primary PCI for STEMI.
      Long-term follow up data from EUROTRANSFER registry.
AB  - OBJECTIVES: Our aim was to describe long-term outcome of OHCA patients in a
      cohort of STEMI patients treated by primary PCI based on the EUROTRANSFER
      Registry data. BACKGROUND: The occurrence of cardiac arrest is associated with
      impaired survival. There are limited number of studies reporting outcome of STEMI
      patients with out-of-hospital cardiac arrest (OHCA) treated by primary
      percutaneous coronary intervention (PCI). The recently published resuscitation
      guidelines of the European Resuscitation Council (ERC) support immediate
      angiography/PCI or fibrinolysis in these patients in order to improve survival.
      METHODS: Consecutive data on 1650 STEMI patients, transferred for primary PCI in
      hospital STEMI networks between November 2005 and January 2007 from 7 countries
      in Europe were gathered. Patients were divided into two groups: OHCA group - 42
      patients and no OHCA group - 1608 patients. RESULTS: Baseline demographics,
      clinical characteristic on admission to cathlab and past medical history were
      similar in both groups. Cardiogenic shock on admission or acute heart failure
      defined as Killip 3+4 was more frequently observed in OHCA group. The in-hospital
      mortality was similar, however, 1-year mortality was 19.1% in the OHCA group vs
      8.1% in no OHCA group (p=0.011) and remained significant after exclusion of
      patients in cardiogenic shock on admission. CONCLUSIONS: STEMI patients treated
      with primary PCI with out-of-hospital cardiac arrest have higher long-term
      mortality than no OHCA patients. However, resuscitation prior to cathlab
      admission is not an independent predictor of long-term adverse outcome. No
      differences in in-hospital mortality were noticed.

PMID- 21958932
TI  - Focused assessment with sonography for trauma (FAST) after successful
      cardiopulmonary resuscitation.

PMID- 21958933
TI  - Casey Eye Institute camera system for recording lens opacities.

PMID- 21958935
TI  - Performance-based tests and self-reported questionnaires provide distinct
      information for the preoperative evaluation of total hip arthroplasty patients.
AB  - Our objectives were to assess relationships between self-reported questionnaires
      and 2-minute walk test (2MWT) and timed get-up-and-go test (TUG) in preoperative
      total hip arthroplasty patients. A total of 162 patients completed the Western
      Ontario and McMaster Universities Osteoarthritis Index and Short Form 36 and
      performed 2MWT and TUG. Correlations between self-reported questionnaires and
      2MWT and TUG were mild to moderate, indicating that the 2MWT and TUG capture
      additional dimensions of preoperative total hip arthroplasty function not
      measured by the Western Ontario and McMaster Universities Osteoarthritis Index
      and Short Form 36. Use of walking aids, female sex, and presence of other painful
      joints were significantly associated with 2MWT, whereas older age and additional
      painful joints were significantly associated with TUG. These 2 tests are easy to
      perform in clinical practice and contribute to a comprehensive assessment of
      preoperative status.

PMID- 21958936
TI  - Letter to the editor.

PMID- 21958937
TI  - Computer navigation vs conventional total knee arthroplasty: five-year functional
      results of a prospective randomized trial.
AB  - Seventy-one patients were randomly allocated to undergo either computer-navigated
      or conventional arthroplasty. A statistically significant improvement in
      alignment was seen in the computer-navigated cohort. Five-year functional outcome
      was assessed using the Knee Society, Short Form-36, Western Ontario and McMaster
      Universities Osteoarthritis Index, and a patient satisfaction score. At 5 years,
      46 patients were available for assessment (24 navigated and 22 conventional
      knees). No patients had undergone revision. No statistically significant
      difference was seen in any component of any measure of outcome between navigated
      and conventional cohorts. Longitudinal data showed function to be well maintained
      with no difference in functional score between 2 and 5 years in either cohort.
      Despite achieving better alignment, 5 years postoperatively, the functional
      outcome with computer-navigated knee arthroplasty appears to be no different to
      that implanted using a conventional jig-based technique.

PMID- 21958938
TI  - A polyethylene liner scratch after revision hip arthroplasty performed to repair
      ceramic fracture.
AB  - A 61-year-old man who had undergone revision total hip arthroplasty in 2000 was
      evaluated at our clinic in 2008, 1 day after feeling an abnormal clicking
      sensation in his left hip. Radiographs showed a fracture of the alumina ceramic
      liner of his acetabular component. A second revision total hip arthroplasty was
      performed with a 28-mm highly crosslinked polyethylene acetabular liner and an
      alumina femoral head. Sixteen months after the second revision, the patient
      experience sudden-onset hip pain. Radiographs revealed a fatigue fracture of the
      neck of a displaced stem. Analysis by scanning electron microscopy of the surface
      of the retrieved alumina ceramic femoral head revealed no scratches or wear, but
      analysis of the highly crosslinked polyethylene socket revealed third-body wear,
      scratches, irregularly shaped dips, and white ceramic particles. Elemental
      analysis of the white particles by an x-ray microanalyzer revealed the presence
      of aluminum and oxygen.

PMID- 21958939
TI  - Electroacupuncture attenuates mechanical and warm allodynia through suppression
      of spinal glial activation in a rat model of neuropathic pain.
AB  - Neuropathic pain remains one of the most difficult clinical pain syndromes to
      treat. It is traditionally viewed as being mediated solely by neurons; however,
      glial cells have recently been implicated as powerful modulators of pain. It is
      known that the analgesic effects of electroacupuncture (EA) are mediated by
      descending pain inhibitory systems, which mainly involve spinal opioid,
      adrenergic, dopaminergic, serotonergic, and cholinergic receptors. However,
      studies investigating the suppressive effects of EA on spinal glial activation
      are rare. In the present study, we assessed the cumulative analgesic effects of
      EA on mechanical and warm allodynia in a rat model of neuropathic pain. We
      investigated the clinical efficacy of EA as long-term therapy and examined its
      effects on spinal glia, matrix metalloproteinase (MMP)-9/MMP-2, proinflammatory
      cytokines and serum immunoglobulin G (IgG) concentration. Rats were randomly
      divided into four groups as follows: the operation group (OP), operation with EA
      non acupoint (EA-NA), operation with EA-ST36 acupoint (EA-ST36), and sham
      operation (shamOP). Following neuropathic or sham surgery, repeated EA was
      performed every other day after the behavioral test. On day 53 after the
      behavioral test, rats were perfused for immunohistochemistry and Western blot
      analysis to observe quantitative changes in spinal glial markers such as OX-42,
      astrocytic glial fibrillary acidic protein (GFAP), MMP-9/MMP-2, and
      proinflammatory cytokines. Allodynia and OX-42/GFAP/MMP-9/MMP-2/tumor necrosis
      factor (TNF)-alpha/interleukin (IL)-1beta activity in the EA-ST36 group was
      significantly reduced, compared to the OP and EA-NA groups, and IgG in EA-ST36
      rats significantly increased. Our results suggest that the analgesic effect of EA
      may be partly mediated via inhibition of inflammation and glial activation and
      repeated EA stimulation may be useful for treating chronic pain clinically.

PMID- 21958940
TI  - Adipokines and stroke: a review of the literature.
AB  - Stroke represents one of the most important menaces to public health. A number of
      modifiable and non-modifiable risk factors have been identified and studied in
      detail; among those, obesity, the new world epidemic, seems to be one of the most
      important in terms of prevention. The discovery of the secretory role of the
      adipose tissue and of adipokines has opened new fields of research. A number of
      studies have been published on their relation to cardiovascular risk and the
      potential of using them as prevention markers. In the present review the
      physiology of leptin, adiponectin and resistin is described and their role in the
      pathogenesis of stroke is examined.

PMID- 21958941
TI  - Soy isoflavones for osteoporosis: an evidence-based approach.
AB  - Effects of soy isoflavones on osteoporosis remain unclear. This review aimed to
      clarify the effect of soy isoflavones on bone mineral density (BMD) and turnover
      markers in menopausal women. PubMed and the Cochrane Library were searched in
      July 2011 for relevant meta-analyses of randomized controlled trials evaluating
      effects of soy isoflavones on BMD and bone turnover markers. Three meta-analyses
      evaluated the effects of soy isoflavones on lumbar spine, total hip, femoral
      neck, and trochanter BMD. Soy isoflavones significantly improved lumbar spine BMD
      in a moderate manner, but did not affect total hip, femoral neck, and trochanter
      BMD in menopausal women. Ingestion of soy isoflavones for six months appeared to
      be enough to exert a beneficial effect on lumbar spine BMD. Two meta-analyses
      evaluated the effects of soy isoflavones on a bone resorption marker (urine
      deoxypyridinoline) and two formation markers (serum alkaline phosphatase and
      osteocalcin). Soy isoflavones significantly decreased urine deoxypyridinoline in
      a moderate manner, but did not affect serum alkaline phosphatase and osteocalcin
      in menopausal women. Soy isoflavones may prevent postmenopausal osteoporosis and
      improve bone strength thus decreasing risk of fracture in menopausal women by
      increasing lumbar spine BMD and decreasing bone resorption marker urine
      deoxypyridinoline. Further studies are needed to address factors affecting the
      magnitude of the beneficial effects of soy isoflavones and to assess the possible
      interactions between soy isoflavones and anti-osteoporosis drugs, and to verify
      effects on BMD of other skeletal sites and other bone turnover markers.

PMID- 21958942
TI  - Improving quality of life in ageing populations: what can volunteering do?
AB  - The year 2011 was declared the 'European Year of Volunteering' to recognise the
      contribution volunteers make to society. Such cross-national events reflect the
      high profile of volunteering and political imperatives to promote it. The purpose
      of this review is to provide a comprehensive review of current knowledge
      (articles published between 2005 and 2011) regarding the role of volunteering in
      improving older people's quality of life (QoL) and to identify areas requiring
      further research. Volunteering was defined as an activity that is freely chosen,
      does not involve remuneration and helps or benefits those beyond an individual's
      immediate family. Our search identified 22 studies and 5 review articles that
      addressed the benefits of volunteering on older people's quality of life. Most of
      the research had been conducted in the United States, Canada and Australia using
      data from longitudinal studies. The majority of the studies concluded that there
      is a positive association between older people's quality of life and engagement
      in volunteering. Due to the study designs and the heterogeneity of the research,
      causality is difficult to demonstrate and the knowledge the studies bring to the
      subject is variable. This review shows that volunteering may help to maintain and
      possibly improve some older adults' quality of life. However, there are still
      major gaps in our understanding of who actually benefits, the social and cultural
      context of volunteering and its role in reducing health and social inequalities.

PMID- 21958943
TI  - Digitized assessment of mammographic breast density--effects of continuous
      combined hormone therapy, tibolone and black cohosh compared to placebo.
AB  - OBJECTIVES: To determine the effects of continuous combined hormone therapy,
      tibolone, black cohosh, and placebo on digitized mammographic breast density in
      postmenopausal women. STUDY DESIGN: A prospective, double-blind, placebo
      controlled study of 154 postmenopausal women randomized to estradiol 2
      mg/norethisterone acetate 1 mg (E2/NETA), tibolone 2.5 mg or placebo and a
      prospective, open, uncontrolled drug safety study, of which 65 postmenopausal
      women were treated with black cohosh. Mammograms, at baseline and after six
      months of treatment, were previously classified according to visual
      quantification scales. MAIN OUTCOME MEASURES: Reanalysis of assessable mammograms
      by digitized quantification of breast density. RESULTS: Treatment groups were
      comparable at baseline. During treatment, both E2/NETA and tibolone significantly
      increased breast density (mean increase 14.3%, p<0.001 and 2.3%, p<0.001,
      respectively), while black cohosh and placebo did not. Twenty-four out of the 43
      women on E2/NETA had an increase in density exceeding 10% and 6 women had an
      increase of 30% or more. In the tibolone group, only one woman had an increase in
      density of more than 10%. The difference in increase in breast density between
      E2/NETA on the one hand and tibolone, black cohosh and placebo on the other was
      highly significant (p<0.0001). CONCLUSIONS: Digitized mammographic breast density
      is a highly sensitive method confirming significant increase in density by
      standard E2/NETA treatment and to a lesser extent by tibolone, whereas black
      cohosh does not influence mammographic breast density during six months
      treatment. Digitized assessment also yields data on individual variation and
      small increases left undetectable by visual classification.

PMID- 21958945
TI  - Premium subsidies and social health insurance: substitutes or complements?
AB  - Premium subsidies have been advocated as an alternative to social health
      insurance. These subsidies are paid if expenditure on health insurance exceeds a
      given share of income. In this paper, we examine whether this approach is
      superior to social health insurance from a welfare perspective. We show that the
      results crucially depend on the correlation of health and productivity. For a
      positive correlation, we find that combining premium subsidies with social health
      insurance is the optimal policy.

PMID- 21958944
TI  - Genetically engineered murine models--contribution to our understanding of the
      genetics, molecular pathology and therapeutic targeting of neuroblastoma.
AB  - Genetically engineered mouse models (GEMM) have made major contributions to a
      molecular understanding of several adult cancers and these results are
      increasingly being translated into the pre-clinical setting where GEMM will very
      likely make a major impact on the development of targeted therapeutics in the
      near future. The relationship of pediatric cancers to altered developmental
      programs, and their genetic simplicity relative to adult cancers provides unique
      opportunities for the application of new advances in GEMM technology. In
      neuroblastoma the well-characterized TH-MYCN GEMM is increasingly used for a
      variety of molecular-genetic, developmental and pre-clinical therapeutics
      applications. We discuss: the present and historical application of GEMM to
      neuroblastoma research, future opportunities, and relevant targets suitable for
      new GEMM strategies in neuroblastoma. We review the potential of these models to
      contribute both to an understanding of the developmental nature of neuroblastoma
      and to improved therapy for this disease.

PMID- 21958946
TI  - Acetyl-L-carnitine and alpha-lipoic acid affect rotenone-induced damage in nigral
      dopaminergic neurons of rat brain, implication for Parkinson's disease therapy.
AB  - Although the mechanisms of neurodegeneration in Parkinson's disease are not fully
      understood, mitochondrial dysfunction, oxidative stress and environmental toxins
      may be involved. The current research was directed to investigate the protective
      role of two bioenergetic antioxidants, acetyl-L-carnitine and alpha-lipoic acid,
      in rotenone-parkinsonian rats. Ninety six male rats were divided into five
      groups. Group I is the vehicle-injected group, group II is the disease control
      group and was injected with six doses of rotenone (1.5 mg/kg/48 h, s.c.). Groups
      III, IV and V received rotenone in addition to acetyl-L-carnitine (100 mg/kg/day,
      p.o.), alpha-lipoic acid (50 mg/kg/day, p.o.) or their combination, respectively.
      Results showed that rotenone-treated rats exhibited bradykinesia and motor
      impairment in the open-field and square bridge tests. In addition, ATP level was
      decreased whereas lipid peroxides and protein carbonyls increased in the striata
      of rotenone-treated rats as compared to vehicle-treated rats. Treatment with
      acetyl-L-carnitine or alpha-lipoic acid improved the motor performance and
      reduced the level of lipid peroxides in rat brains as compared to rotenone group.
      Further, ATP production was enhanced along with acetyl-L-carnitine treatments
      (p<=0.05). Taken together, our study reinforces the view that acetyl-L-carnitine
      and alpha-lipoic acid are promising candidates for neuroprotection in Parkinson's
      disease.

PMID- 21958947
TI  - Centrally mediated antinociceptive effects of cannabinoid receptor ligands in rat
      models of nociception.
AB  - The endogenous nonapeptide hemopressin (HE) demonstrates potent block of the
      cannabinoid subtype-1 (CB1) receptor in vitro and robust antinociception in vivo.
      The current study evaluated the effects of centrally administered HE in
      mechanistically distinct pre-clinical rat models of pain-the hot plate test and
      the hind paw formalin test. The non-subtype selective CB receptor agonist WIN
      55,212-2 was tested concurrently as a positive control. In the hot plate test,
      neither intrathecal (i.t.) HE nor WIN 55,212-2 significantly altered the latency
      to respond to noxious heat. By contrast, i.t. HE and WIN 55,212-2 significantly
      reduced pain-related behaviors in the formalin test. Possible HE functionality as
      a CB1 receptor antagonist at the spinal level was evaluated in the formalin test.
      Intrathecal pretreatment with HE did not attenuate the antinociceptive effect of
      i.t. WIN 55,212-2. However, pretreatment with the CB1 receptor antagonist
      rimonabant did; i.t. rimonabant pretreatment was not antinociceptive. Potential
      supraspinal antinociceptive activity of HE was also evaluated. Whereas
      intracerebroventricular (i.c.v.) injection of WIN 55,212-2 reduced pain-related
      behaviors in the formalin test, interestingly, i.c.v. HE increased behaviors. In
      the current study, an antinociceptive effect with the CB receptor ligand HE was
      obtained under the specific condition of tissue injury and not in the uninjured
      state. Thus, HE could be a useful analgesic peptide with a novel spinal mechanism
      of action.

PMID- 21958948
TI  - Intensive glucose lowering and cognition in type 2 diabetes.

PMID- 21958950
TI  - Surgery for pseudoaneurysm of the ascending aorta under moderate hypothermia.
AB  - Pseudoaneurysm of the ascending aorta is a rare complication after cardiac
      surgery. Particularly, pseudoaneurysm due to postoperative infection in the
      ascending aorta requires surgical treatment with antibiotics. If a large sized
      pseudoaneurysm is located at the retrosternal space, then there is a very high
      risk of massive bleeding from rupture during performance of resternotomy. To
      avoid this risk, we performed femoro-femoral bypass under moderate hypothermia
      with transient circulatory arrest, and we report here on the successful result of
      this case.

PMID- 21958951
TI  - Host CD25+CD4+Foxp3+ regulatory T cells primed by anti-CD137 mAbs inhibit graft
      versus-host disease.
AB  - CD25(+)CD4(+)Foxp3(+) regulatory T cells (Tregs) play a pivotal role in the
      maintenance of self-tolerance and regulation of immune responses. Previous
      studies have demonstrated that CD137 signals can promote proliferation and
      survival of Tregs in vitro. Here, we show that in vivo CD137-induced expansion of
      Tregs in naive mice was dependent upon IL-2 secreted by memory T cells. Tregs
      primed by anti-CD137 mAbs had a higher immunosuppressive capacity.
      Preconditioning with anti-CD137 mAbs significantly inhibited graft-versus-host
      disease (GVHD) in the C57BL/6 -> (C57BL/6 * DBA/2) F1 acute GVHD model. In this
      disease model, a high proportion of host Tregs remained long-term in the
      recipient spleen, whereas donor hematopoietic cells replaced other host bone
      marrow-derived cells. Transient depletion of Tregs before transfer of donor cells
      completely abrogated the inhibitory effect of anti-CD137 mAbs on GVHD. In
      addition, adoptive transfer of anti-CD137-primed Tregs ameliorated GVHD. Our
      results demonstrate that it is possible to enhance the survival and/or the
      immunosuppressive activity of host Tregs in nonmyeloablative GVHD, and that 1 way
      of accomplishing this is through the prophylactic use of anti-CD137 mAbs in
      nonmyeloablative GVHD.

PMID- 21958952
TI  - How old is too old for in vitro maturation (IVM) treatment?
AB  - OBJECTIVE: Fertility declines with age. A study of the outcomes of in vitro
      maturation (IVM) in women of different ages has not been reported to date. The
      aim of our study was to evaluate the impact of age on treatment response and on
      pregnancy rates after IVM treatment. STUDY DESIGN: We reviewed the data of all
      IVM cycles and recorded the total number of oocytes, total metaphase II (MII)
      oocytes, the number and quality of embryos as well as pregnancy rates. The main
      outcome measures were number and maturity of retrieved oocytes and pregnancy
      rates. RESULTS: Compared to cycles in women <=25 years, the number of oocytes and
      total MII oocytes were significantly lower in women over 40 years. The number of
      good quality embryos in women <=25 years (3.6+/-1.7) was higher than in women
      aged 40 years (0.8+/-1.2, P<0.0001). The ongoing pregnancy rates in women aged 20
      25 years were 36.8%, 26-35 years were 30.0% and in those 36-39 years were 31.9%.
      No clinical pregnancy was observed in women over the age of 40. CONCLUSION: Women
      over 40 years are poor candidates for IVM treatment.

PMID- 21958953
TI  - Off-label use of misoprostol for labor induction: a nation-wide survey in
      Switzerland.
AB  - OBJECTIVE: Off-label use of drugs is frequent in obstetrical practice. No data
      however are available about nation-wide off-label use in obstetrics regarding
      frequency and patient information. The objective of our study was to assess the
      clinical practice of off-label use of misoprostol for labor induction. STUDY
      DESIGN: We performed a prospective nation-wide survey study by means of a
      validated questionnaire in three languages in Switzerland. All registered
      obstetricians/gynaecologists in Switzerland were included. Of 1100 subjects, 725
      (66%) answered the questionnaire; 69 subjects were excluded because they were not
      actively practicing OB/GYN, resulting in a total of 656 questionnaires included
      in the analysis. RESULTS: A total of 512 out of 656 obstetricians/gynaecologists
      (78%) use misoprostol for labor induction. The most frequent administration route
      of misoprostol is intravaginal (86%), in a single dose of 50MUg (94%), at a dose
      interval range from 4 to 6h (85%). Among the users of misoprostol, 314 (61%)
      answered that they do not inform their patients about the off-label use of the
      medication. Among the non-users of misoprostol, the main reason for non-use is
      absent license for obstetric indications (48%) and non-availability (14%). If
      misoprostol were to be licensed for this indication, and commercially available,
      69% of current non-users would use it. Non-users of misoprotol use prostaglandin
      E2 vaginal gel, ovules or slow-release vaginal insert, and oxytocin for labor
      induction. CONCLUSION: Misoprostol is the single most commonly used drug for
      labor induction in Switzerland, although it is not licensed and although there
      are effective, licensed alternative drugs available. A minority of practitioners
      inform the patients about the off-label use.

PMID- 21958954
TI  - Neonatal outcome of macrosomic infants: an analysis of a two-year period.
AB  - OBJECTIVE: To assess the neonatal outcome of macrosomic neonates in
      uncomplicated, singleton, term deliveries. STUDY DESIGN: A retrospective analysis
      was performed on 5738 live-born term neonates born in the period 2008-2009. The
      neonatal outcomes were compared between two birth weight (BW) groups: the
      macrosomic neonates born with BW>=4000g and a control group: 2500-3999g. There
      were 410 (7.1%) neonates in the macrosomic group, 4757 (82.9%) in the control
      group, while 571 (10.0%) were less than 2500g at birth. A correlation analysis of
      two subgroups of the macrosomic neonates (4000-4499g vs. >=4500g) was also
      carried out. RESULTS: The rate of caesarean section (CS) was significantly higher
      in the macrosomic group as compared with the control group (49.3% vs. 39.9%), as
      were the prevalences of hypoglycaemia (6.1% vs. 2.9%), adrenal haemorrhage (0.98%
      vs. 0.15%) and the male to female ratio (2.15 vs. 0.95). The rate of icterus was
      significantly higher in the control group (30.4% vs. 18.5%). The macrosomic
      subgroups were similar in many aspects, but we found significantly more neonates
      in the higher weight subgroup as regards a low Apgar score, clavicle fracture and
      the need for intensive care. CONCLUSIONS: The macrosomic infants were born in
      good general condition, although those with BW >=4500g more frequently had an
      adverse outcome. The macrosomic and control groups' data revealed significant
      differences in the rate of CS, the male to female ratio, hypoglycaemia and
      adrenal haemorrhage.

PMID- 21958955
TI  - Methods for assessing fracture risk prediction models: experience with FRAX in a
      large integrated health care delivery system.
AB  - Area under the receiver operating characteristics (AUROC) curve is often used to
      evaluate risk models. However, reclassification tests provide an alternative
      assessment of model performance. We performed both evaluations on results from
      FRAX (World Health Organization Collaborating Centre for Metabolic Bone Diseases,
      University of Sheffield, UK), a fracture risk tool, using Kaiser Permanente
      Northern California women older than 50yr with bone mineral density (BMD)
      measured during 1997-2003. We compared FRAX performance with and without BMD in
      the model. Among 94,489 women with mean follow-up of 6.6yr, 1579 (1.7%) sustained
      a hip fracture. Overall, AUROCs were 0.83 and 0.84 for FRAX without and with BMD,
      suggesting that BMD did not contribute to model performance. AUROC decreased with
      increasing age, and BMD contributed significantly to higher AUROC among those
      aged 70yr and older. Using an 81% sensitivity threshold (optimum level from
      receiver operating characteristic curve, corresponding to 1.2% cutoff), 35% of
      those categorized above were reassigned below when BMD was added. In contrast,
      only 10% of those categorized below were reassigned to the higher risk category
      when BMD was added. The net reclassification improvement was 5.5% (p<0.01). Two
      versions of this risk tool have similar AUROCs, but alternative assessments
      indicate that addition of BMD improves performance. Multiple methods should be
      used to evaluate risk tool performance with less reliance on AUROC alone.

PMID- 21958957
TI  - Biological invasions in the 21st century: ecological impacts, predictions, and
      management across land and sea.

PMID- 21958956
TI  - Axonal damage in the making: neurofilament phosphorylation, proton mobility and
      magnetisation transfer in multiple sclerosis normal appearing white matter.
AB  - AIMS: Multiple sclerosis (MS) leaves a signature on the phosphorylation and thus
      proton binding capacity of axonal neurofilament (Nf) proteins. The proton binding
      capacity in a tissue is the major determinant for exchange between bound and free
      protons and thus the magnetisation transfer ratio (MTR). This study investigated
      whether the MTR of non-lesional white matter (NLWM) was related to the brain
      tissue concentration of neurofilament phosphoforms. METHODS: Unfixed post-mortem
      brain slices of 12 MS patients were analysed using MTR, T1 at 1.5 T. Blocks
      containing NLWM were processed for embedding in paraffin and inspected
      microscopically. Adjacent tissue was microdissected, homogenised and specific
      protein levels were quantified by ELISA for the Nf heavy chain (NfH)
      phosphoforms, glial fibrillary acidic protein (GFAP), S100B and ferritin.
      RESULTS: Averaged hyperphosphorylated NfH (SMI34) but not phosphorylated NfH
      (SMI35) levels were different between individual patients NLWM. The concentration
      of hyperphosphorylated NfH-SMI34 correlated with T1 (R=0.70, p=0.0114) and -
      inversely - with MTR (R=-0.73, p=0.0065). NfH-SMI35 was not correlated to any of
      the MR indices. CONCLUSIONS: Post-translational modifications of axonal proteins
      such as phosphorylation of neurofilaments occur in NLWM and may precede
      demyelination. The resulting change of proton mobility influences MTR and T1.
      This permits the in vivo detection of these subtle tissue changes on a proteomic
      level in patients with MS.

PMID- 21958958
TI  - A randomized, double-blind, placebo-controlled trial of paracetamol and
      ketoprofren lysine salt for pain control in children with pharyngotonsillitis
      cared by family pediatricians.
AB  - BACKGROUND: To evaluate the analgesic effect and tolerability of paracetamol
      syrup compared to placebo and ketoprofen lysine salt in children with
      pharyngotonsillitis cared by family pediatricians. METHODS: A double-blind,
      randomized, placebo-controlled trial of a 12 mg/kg single dose of paracetamol
      paralleled by open-label ketoprofren lysine salt sachet 40 mg. Six to 12 years
      old children with diagnosis of pharyngo-tonsillitis and a Children's Sore Throat
      Pain (CSTP) Thermometer score > 120 mm were enrolled. Primary endpoint was the
      Sum of Pain Intensity Differences (SPID) of the CSTP Intensity scale by the
      child. RESULTS: 97 children were equally randomized to paracetamol, placebo or
      ketoprofen. Paracetamol was significantly more effective than placebo in the SPID
      of children and parents (P < 0.05) but not in the SPID reported by investigators,
      1 hour after drug administration. Global evaluation of efficacy showed a
      statistically significant advantage of paracetamol over placebo after 1 hour
      either for children, parents or investigators. Patients treated in open fashion
      with ketoprofen lysine salt, showed similar improvement in pain over time. All
      treatments were well-tolerated. CONCLUSIONS: A single oral dose of paracetamol or
      ketoprofen lysine salt are safe and effective analgesic treatments for children
      with sore throat in daily pediatric ambulatory care.

PMID- 21958959
TI  - B cells in clinical transplantation tolerance.
AB  - The rarity of tolerance following clinical transplantation has complicated the
      study of the responsible mechanisms. Several recent studies of kidney transplant
      recipients have demonstrated an association between increased numbers of B cells
      with less mature, inhibitory phenotypes and a state of tolerance. While a growing
      body of evidence from experimental models supports a role for B cells in
      regulating or suppressing immune responses, a causative role for B cells in
      clinical transplantation tolerance has yet to be proven. If B cells are
      conclusively shown to participate in the development of transplantation
      tolerance, it will be important to define the responsible mechanisms in order to
      design monitoring assays and immunosuppressive regimens that favor the
      development of tolerance.

PMID- 21958960
TI  - Humoral immunity and antibody-mediated rejection in solid organ transplantation.
AB  - The humoral arm of the immune system provides robust protection against
      extracellular pathogens via the production of antibody molecules that neutralize
      or facilitate the destruction of microorganisms. However, the humoral immune
      system also provides a significant barrier to solid organ transplantation due to
      the antibody-mediated recognition of non-self proteins and carbohydrates
      expressed on transplanted organs. Historically, the presence of donor-specific
      antibodies (DSA) that recognize donor HLA molecules, incompatible ABO blood group
      antigens and other endothelial or xenogeneic antigens was considered a
      contraindication to transplantation. However, recent advances in antibody testing
      and immunosuppressive therapies have made it possible to cross certain antibody
      barriers successfully. In this article, we review our current understanding of
      antibody-mediated processes in solid organ transplantation and discuss the
      clinically available treatment options for preventing and treating antibody
      mediated rejection.

PMID- 21958961
TI  - The neuroprotective enzyme CYP2D6 increases in the brain with age and is lower in
      Parkinson's disease patients.
AB  - Cytochrome P450 2D6 (CYP2D6) is a drug-metabolizing enzyme expressed in the brain
      that also metabolizes endogenous neural compounds (e.g., catecholamines) and
      inactivates neurotoxins (e.g., 1-methyl-4-thenyl-1,2,3,6-tetrahydropyridine;
      MPTP). Genetically poor CYP2D6 metabolizers are at higher risk for developing
      Parkinson's disease (PD), a risk that increases with exposure to pesticides. As
      age is a risk factor for PD we measured the ontogenic expression of CYP2D6 in
      human brain, and compared brain CYP2D6 levels in PD cases with age-matched
      controls. CYP2D6 increased from fetal to 80 years of age (n = 76), exhibiting 3
      distinct phases of change. Compared with PD controls, PD cases had approximately
      40% lower CYP2D6 levels in the frontal cortex, cerebellum, and the hippocampus,
      even when controlling for CYP2D6 genotype. In contrast, CYP2D6 levels in cases
      were similar to controls in PD-affected brain areas, the substantia nigra, and
      caudate, consistent with higher astrocytic and cellular CYP2D6 staining observed
      in PD cases. In summary, the lower CYP2D6 levels in PD cases may have reduced
      their ability to inactivate PD-causing neurotoxins contributing to their disease
      risk.

PMID- 21958962
TI  - Plasma beta amyloid and the risk of Alzheimer's disease in Down syndrome.
AB  - Extracellular deposition of amyloid beta peptide (Abeta) has been implicated as a
      critical step in the pathogenesis of Alzheimer's disease (AD). In Down syndrome
      (DS), Alzheimer's disease is assumed to be caused by the triplication and
      overexpression of the gene for amyloid precursor protein (APP), located on
      chromosome 21. Plasma concentrations of Abeta1-40 and Abeta1-42 were determined
      in a population based study of 506 persons with DS, who were screened annually
      for dementia. We used Cox proportional hazards models to determine the risk of
      dementia. Demented persons with DS have a significantly higher plasma Abeta1-40
      concentration than the nondemented (p = 0.05). Those with the highest
      concentrations of Abeta1-40 and Abeta1-42 have a higher risk to develop dementia.
      The risk to develop dementia during follow-up (mean 4.7 years) increased to 2.56
      (95% confidence interval, 1.39-4.71) for Abeta1-42 and 2.16 (95% confidence
      interval, 1.14-4.10) for Abeta1-40. High plasma concentration of plasma Abeta1-40
      and Abeta1-42 are determinants of the risk of dementia in persons with DS.

PMID- 21958963
TI  - Interaction between NH(2)-tau fragment and Abeta in Alzheimer's disease
      mitochondria contributes to the synaptic deterioration.
AB  - Although amyloid beta (Abeta) peptide can promote tau pathology and its toxicity
      is concurrently tau-dependent, the underlying mechanisms of the in vivo interplay
      of these proteins remain unsolved. Structural and functional mitochondrial
      alterations play an early, precipitating role in synaptic failure of Alzheimer's
      disease (AD) pathogenesis and an aggravated mitochondrial impairment has been
      described in triple APP/PS/tau transgenic mice carrying both plaques and tangles,
      if compared with mice overexpressing tau or amyloid precursor protein (APP)
      alone. Here, we show that a neurotoxic aminoterminal (NH(2))-derived tau fragment
      mapping between 26 and 230 amino acids of the human tau40 isoform (441 amino
      acids)-but not the physiological full-length protein-preferentially interacts
      with Abeta peptide(s) in human AD synapses in association with mitochondrial
      adenine nucleotide translocator-1 (ANT-1) and cyclophilin D. The two peptides
      Abeta 1-42 and the smaller and more potent NH(2)-26-44 peptide of the longest 20
      22 kDa NH(2)-tau fragment-inhibit the ANT-1-dependent adenosine diphosphate
      adenosine triphosphate (ADP/ATP) exchange in a noncompetitive and competitive
      manner, respectively, and together further aggravate the mitochondrial
      dysfunction by exacerbating the ANT-1 impairment. Taken together, these data
      establish a common, direct and synergistic toxicity of pathological APP and tau
      products on synaptic mitochondria and suggest potential, new pathway(s) and
      target(s) for a combined, more efficient therapeutic intervention of early
      synaptic dysfunction in AD.

PMID- 21958964
TI  - Paired-pulse afferent modulation of TMS responses reveals a selective decrease in
      short latency afferent inhibition with age.
AB  - Changes in motor cortical excitability were examined in 2 groups of participants,
      young (18-30 years of age, n = 25) and senior (65-82 years of age, n = 31), using
      paired-pulse afferent stimulation with transcranial magnetic stimulation (TMS).
      Motor evoked potentials (MEPs) elicited by TMS at suprathreshold intensity (120%
      motor threshold) were first recorded in unconditioned trials (TMS alone) and then
      in conditioned trials, in which TMS pulses were preceded by median nerve
      stimulation at 3 different interstimulus intervals (ISI; 20, 50, and 200 ms).
      Conditioning of MEP responses revealed a similar pattern of modulation in the 2
      age groups, with 2 periods of inhibition at 20- and 200-ms ISIs, separated by a
      period in which MEPs tended to return to baseline at a 50-ms ISI. Afferent
      induced inhibition at the short interval (i.e., SAI 20-ms ISI), was selectively
      reduced in seniors, with half of them showing either low or no MEP suppression.
      Age-associated changes in SAI level were also good predictors of performance on
      tests of processing speed and dexterity. The selective decrease in SAI exhibited
      by many seniors is consistent with reported alterations in intracortical
      inhibition with age. Our observations also highlight the potential value of SAI,
      as a putative marker of central cholinergic activity, in predicting declines in
      motor and cognitive function with age.

PMID- 21958949
TI  - Effects of intensive glucose lowering on brain structure and function in people
      with type 2 diabetes (ACCORD MIND): a randomised open-label substudy.
AB  - BACKGROUND: People with type 2 diabetes are at risk of cognitive impairment and
      brain atrophy. We aimed to compare the effects on cognitive function and brain
      volume of intensive versus standard glycaemic control. METHODS: The Memory in
      Diabetes (MIND) study was done in 52 clinical sites in North America as part of
      Action to Control Cardiovascular Risk in Diabetes (ACCORD), a double two-by-two
      factorial parallel group randomised trial. Participants (aged 55-80 years) with
      type 2 diabetes, high glycated haemoglobin A(1c) (HbA(1c)) concentrations (>7.5%;
      >58 mmol/mol), and a high risk of cardiovascular events were randomly assigned to
      receive intensive glycaemic control targeting HbA(1c) to less than 6.0% (42
      mmol/mol) or a standard strategy targeting HbA(1c) to 7.0-7.9% (53-63 mmol/mol).
      Randomisation was via a centralised web-based system and treatment allocation was
      not masked from clinic staff or participants. We assessed our cognitive primary
      outcome, the Digit Symbol Substitution Test (DSST) score, at baseline and at 20
      and 40 months. We assessed total brain volume (TBV), our primary brain structure
      outcome, with MRI at baseline and 40 months in a subset of participants. We
      included all participants with follow-up data in our primary analyses. In
      February, 2008, raised mortality risk led to the end of the intensive treatment
      and transition of those participants to standard treatment. We tested our
      cognitive function hypotheses with a mixed-effects model that incorporated
      information from both the 20 and 40 month outcome measures. We tested our MRI
      hypotheses with an ANCOVA model that included intracranial volume and factors
      used to stratify randomisation. This study is registered with ClinicalTrials.gov,
      number NCT00182910. FINDINGS: We consecutively enrolled 2977 patients (mean age
      62.5 years; SD 5.8) who had been randomly assigned to treatment groups in the
      ACCORD study. Our primary cognitive analysis was of patients with a 20-month or
      40-month DSST score: 1378 assigned to receive intensive treatment and 1416
      assigned to receive standard treatment. Of the 614 patients with a baseline MRI,
      we included 230 assigned to receive intensive treatment and 273 assigned to
      receive standard treatment in our primary MRI analysis at 40 months. There was no
      significant treatment difference in mean 40-month DSST score (difference in mean
      0.32, 95% CI -0.28 to 0.91; p=0.2997). The intensive-treatment group had a
      greater mean TBV than the standard-treatment group (4.62, 2.0 to 7.3; p=0.0007).
      INTERPRETATION: Although significant differences in TBV favoured the intensive
      treatment, cognitive outcomes were not different. Combined with the non
      significant effects on other ACCORD outcomes, and increased mortality in
      participants in the intensive treatment group, our findings do not support the
      use of intensive therapy to reduce the adverse effects of diabetes on the brain
      in patients with similar characteristics to those of our participants. FUNDING:
      US National Institute on Aging and US National Heart, Lung, and Blood Institute.

PMID- 21958965
TI  - Pharmacokinetics of brucine after intravenous and oral administration to rats.
AB  - The toxicity depending on both dose and administration route is the major
      obstacle to the development of brucine, a bioactive alkaloid from Semen Strychni.
      In this study, the apparent partition coefficient and plasma protein binding
      extent of brucine were determined. In addition, the dose-dependency of the
      pharmacokinetics of brucine was investigated. Three intravenous (2.5, 5 and 10
      mg/kg) and three oral (10, 20 and 40 mg/kg) doses were administered to rats.
      After intravenous administration, the systemic clearance was reduced and AUC was
      nonlinearly increased as a function of dose. Upon oral administration, brucine
      was rapidly absorbed (T(max)<0.5h), which was consistent with previously reported
      high Caco-2 P(app) values. The increase in AUC was proportional to the increase
      in dose. The oral bioavailability (F) did not vary with the dose (F=40.31%,
      47.15% and 43.02% for 10, 20, 40 mg/kg doses, respectively). However, the dose
      proportionality was not observed with C(max). The values of C(max)/Dose were
      calculated to be 92.92+/-45.83, 55.73+/-24.01 and 36.29+/-22.44 MUg/L for 10, 20
      and 40 mg/kg, respectively. The results of dose-dependent pharmacokinetic
      behavior under different administration routes may account for the significantly
      different toxicities of brucine between intravenous and oral administration.

PMID- 21958966
TI  - Awara (Astrocaryum vulgare M.) pulp oil: chemical characterization, and anti
      inflammatory properties in a mice model of endotoxic shock and a rat model of
      pulmonary inflammation.
AB  - Awara (Astrocaryum vulgare M.) is a palm fruit mainly used in nutrition. We
      analysed the pulp oil for fatty acid, tocopherol, carotenoid, and phytosterol and
      we evaluated whether this oil may attenuate inflammation in vivo. In an endotoxic
      shock model, awara pulp oil treatment decreased pro-inflammatory cytokines and
      increased anti-inflammatory cytokines. In a pulmonary inflammation model, awara
      pulp oil treatment reduced eosinophil and lymphocyte numbers recovered into the
      broncho-alveolar lavages. These results suggest that awara pulp oil
      administration can efficiently counteract an acute and chronic inflammatory
      response in vivo that is probably mediated by fatty acids and minor compounds.

PMID- 21958967
TI  - Antitussive, expectorant and anti-inflammatory alkaloids from Bulbus Fritillariae
      Cirrhosae.
AB  - The primary objective of this study is to evaluate the antitussive, expectorant
      and anti-inflammatory effects of alkaloids imperialine (I), chuanbeinone (II),
      verticinone (III), and verticine (IV), which were isolated from the Bulbus
      Fritillariae Cirrhosae (BFC) using phytochemical method. The results showed that
      all the alkaloids significantly inhibited cough frequency and increased latent
      period of cough in mice induced by ammonia. Besides, imperialine(I),
      verticinone(III) and verticine(IV) markedly enhanced mice's tracheal phenol red
      output in expectorant evaluation, and imperialine(I), chuanbeinone(II)
      significantly inhibited the development of ear edema in a dose-dependent manner
      in anti-inflammatory assessment. Moreover, important differences were found among
      the structure-activity relationships for the four alkaloids. These results
      confirmed that the four alkaloids imperialine, chuanbeinone, verticinone and
      verticine may be the active ingredients of the Bulbus F. Cirrhosae (BFC).

PMID- 21958969
TI  - The 1,4-naphthoquinone derivative from Pyrola rotundifolia activates AMPK
      phosphorylation in C2C12 myotubes.
AB  - An aqueous ethanol extract of Pyrola rotundifolia L. induced AMP-activated
      protein kinase (AMPK) phosphorylation in C2C12 myotubes. The bioassay-guided
      fractionation of the extract led to the isolation a 2-methyl-7-hydroxymethyl-1,4
      naphthoquinone, or a 7'-hydroxy-chimaphilin, which showed concentration-dependent
      AMPK phosphorylation activity at 2.5-20 MUg/ml. At a concentration of 10 MUg/ml
      (50 MUM), an approximately four-fold increase in the AMPKalpha(Thr172)
      phosphorylation level was observed. The stimulatory effect of naphthoquinone on
      AMPK activity was comparable to that of known compounds found in natural sources
      that activate the AMPK signaling pathway.

PMID- 21958968
TI  - Anti-inflammatory activity of patchouli alcohol isolated from Pogostemonis Herba
      in animal models.
AB  - Pogostemonis Herba has long been used in traditional Chinese medicine for the
      treatment of inflammatory disorders. Patchouli alcohol (PA), a tricyclic
      sesquiterpene isolated from Pogostemonis Herba, is known to possess a variety of
      pharmacological activities. The present study aimed to investigate the in vivo
      anti-inflammatory effect of PA using two common inflammatory animal models i.e.,
      xylene-induced ear edema in mice and carrageenan-induced paw edema in rats. The
      degree of edema in both inflammatory animals, as well as the protein and mRNA
      expression of some inflammatory mediators including tumor necrosis factor-alpha
      (TNF-alpha), interleukin-1beta (IL-1beta), prostaglandin E2 (PGE2) and nitric
      oxide (NO) in the hind paw of carrageenan-treated rats were measured. Results
      showed that PA (10-40 mg/kg) significantly inhibited the ear edema induced by
      xylene in mice and the paw edema induced by carrageenan in rats. In addition,
      treatment with PA (10-40 mg/kg) also dose-dependently decreased the production of
      TNF-alpha, IL-1beta, PGE2 and NO in the hind paw of carrageenan-treated rats.
      Furthermore, PA treatment also suppressed the mRNA expression of TNF-alpha, IL
      1beta, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the
      hind paw of carrageenan-treated rats. These results suggest that PA possesses
      potent anti-inflammatory activity, which may be mediated, at least in part, by
      down-regulating the mRNA expression of a panel of inflammatory mediators
      including TNF-alpha, IL-1beta, iNOS and COX-2.

PMID- 21958970
TI  - Antibacterial activity of povidone-iodine against an artificial biofilm of
      Porphyromonas gingivalis and Fusobacterium nucleatum.
AB  - OBJECTIVE: To investigate the antibacterial activity of povidone-iodine (PVP-I)
      on an artificial dual species biofilm of periodontal pathogens. DESIGN:
      Porphyromonas gingivalis or Fusobacterium nucleatum grown in broth culture was
      inoculated on polycarbonate membrane (PCM) tissue culture inserts. After
      incubation for 72 h, PVP-I solutions were applied to the biofilm for the time
      period ranging from 0.5 to 5 min. After addition of a deactivator, each PCM was
      removed and the biofilm on the PCM was serially diluted and plated on blood agar
      plates and cultured anaerobically for 7 days. Then viable bacteria were
      enumerated. RESULTS: In the dual species biofilm model, F. nucleatum showed an
      approximately 200-fold increase in viable counts when compared with mono
      microbial biofilm. In dual species biofilm, PVP-I with concentration equal to or
      greater than 2% was required to significantly reduce P. gingivalis and F.
      nucleatum. When the contact time of PVP-I was increased to 1 min or greater, no
      difference in antibacterial activity of PVP-I was observed in any concentration.
      CONCLUSION: These results suggest that 30s application of 2% PVP-I would be
      effective in suppressing both P. gingivalis and F. nucleatum in dual-species
      biofilm, and this provides clinical implication for the control of subgingival
      biofilm.

PMID- 21958971
TI  - Body composition and fat distribution among older Jat females: a rural-urban
      comparison.
AB  - The aim of the present cross-sectional study is to describe and compare age
      related changes in body composition and fat patterning among rural and urban Jat
      females of Haryana State, India. A total of 600 females (rural=300, urban=300),
      ranging in age from 40 to 70 years were selected by the purposive sampling
      method. Body weight, height, two circumferences (waist and hip) and skinfold
      thickness at five different sites (biceps, triceps, calf, subscapular, and supra
      iliac) were taken on each participant. To study total adiposity, indices such as
      body mass index (BMI), grand mean thickness (GMT), total body fat and percentage
      fat were analyzed statistically. The fat distribution pattern was studied using
      waist/hip ratio, subscapular/triceps ratio and responsiveness of five skinfold
      sites towards accumulation of fat at different sites with advancing age. Results
      indicate a decline in almost every dimension including level of fatness between
      the mid-fourth and mid-fifth decades of life in both rural and urban females.
      Urban Jat females were heavier (57.36 kg vs. 56.07 kg, p>0.05) and significantly
      taller (1553.3mm vs. 1534.5mm, p<0.001) than their rural counterparts. Urban
      females also exhibited higher mean values for both the circumferences, five
      skinfold thicknesses as well as for lean body mass, total fat and percentage fat
      than the rural females. This is also evident from their higher mean values for
      body mass index and grand mean thickness. Waist/hip ratio values in rural and
      urban females showed upper body fat predominance, with urban females having
      relatively more abdominal fat. Results of subscapular/triceps ratio showed that
      rural and urban females gained proportionally similar amounts of subcutaneous fat
      at trunk and extremity sites until 45 years of age. Subsequently trunk skinfolds
      increased relatively more in thickness. The magnitude of this increase was
      comparatively greater in rural females up to 55 years and among urban females
      from 55 to 70 years. The profiles of subcutaneous fat accumulation and
      sensitivity of each skinfold site also revealed more fat deposition in the trunk
      region compared to extremities in both rural and urban females. The present study
      demonstrated differential rates of fat redistribution among rural and urban
      females.

PMID- 21958972
TI  - The development of dental research in Argentinean biological anthropology:
      current state and future perspectives.
AB  - The aim of this paper is to conduct a historical analysis of the research
      oriented studies related to dental anthropology in Argentina, evaluate its
      current state and discuss future expectations and perspectives. In this country,
      anthropological studies based on analysis of dentition have been scarce and even
      temporarily discontinued, since they began in the late nineteenth century, simply
      following the course of the predominant theoretical and methodological approaches
      over time. Early papers, guided mainly by evolutionary ideas, were oriented
      towards establishing the taxonomic position of humans through the description and
      comparison of morphological and morphometric aspects of the dental crown and
      root. Later studies mainly described types of intentional modifications (i.e.
      dental mutilations) and tooth wear in the context of Historic-Cultural School.
      However, they failed to constitute valid lines of research over time. In recent
      years, there has been a significant change in dental studies, mainly as a result
      of the interest in evaluating the adaptive aspects of human populations within
      biocultural settings. One of the most relevant lines of studies has been the
      bioarchaeological analysis of health and stress indicators, such as enamel
      hypoplasia, caries and tooth wear in hunter-gatherer and farmer societies. More
      recently, the study of discrete and metric dental traits began, with a goal to
      contribute to the study of evolution and inter-populational biological relations
      among South American groups. Since teeth contain valuable information not only
      about the environment in which the individual lived, but also about the action of
      neutral and non-neutral factors on human groups, the consolidation of ongoing
      studies will contribute to knowledge of various aspects of the adaptation and
      evolution of native American populations.

PMID- 21958973
TI  - The Sequential Organ Failure Assessment score and copeptin for predicting
      survival in ventilator-associated pneumonia.
AB  - INTRODUCTION: Ventilator-associated pneumonia remains the most common nosocomial
      infection in the critically ill and contributes to significant morbidity.
      Eventual decisions regarding withdrawal or maximal therapy are demanding and rely
      on physicians' experience. Additional objective tools for risk assessment may
      improve medical judgement. Copeptin, reflecting vasopressin release, as well as
      the Sequential Organ Failure Assessment (SOFA) score, reflecting the individual
      degree of organ dysfunction, might qualify for survival prediction in ventilator
      associated pneumonia. We investigated the predictive value of the SOFA score and
      copeptin in ventilator-associated pneumonia. METHODS: One hundred one patients
      with ventilator-associated pneumonia were prospectively assessed. Death within 28
      days after ventilator-associated pneumonia onset was the primary end point.
      RESULTS: The SOFA score and the copeptin levels at ventilator-associated
      pneumonia onset were significantly elevated in nonsurvivors (P = .002 and P =
      .017, respectively). Both markers had different time courses in survivors and
      nonsurvivors (P < .001 and P = .006). Mean SOFA (average SOFA of 10 days after
      VAP onset) was superior in predicting 28-day survival as compared with SOFA and
      copeptin at ventilator-associated pneumonia onset (area under the curve, 0.90 vs
      0.73 and 0.67, respectively). CONCLUSIONS: The predictive value of serial
      measured SOFA significantly exceeds those of single SOFA and copeptin
      measurements. Serial SOFA scores accurately predict outcome in ventilator
      associated pneumonia.

PMID- 21958974
TI  - Impact of high-flow nasal cannula oxygen therapy on intensive care unit patients
      with acute respiratory failure: a prospective observational study.
AB  - PURPOSE: The purpose of this study was to determine the impact of high-flow nasal
      cannula oxygen (HFNC) on patients with acute respiratory failure (ARF) in
      comparison with conventional oxygen therapy. MATERIALS AND METHODS: This was a
      prospective observational study. Patients with persistent ARF despite oxygen with
      conventional facemask without indication for immediate intubation were treated
      with HFNC oxygen. Clinical respiratory parameters and arterial blood gases were
      compared under conventional and HFNC oxygen therapy. RESULTS: Twenty patients,
      aged 59 years (38-75 years) and SAPS2 (simplified acute physiology score) 33
      (26.5-38), were included in the study. Etiology of ARF was mainly pneumonia (n =
      11), sepsis (n = 3), and miscellaneous (n = 6). Use of HFNC enabled a significant
      reduction of respiratory rate, 28 (26-33) vs 24.5 (23-28.5) breath per minute (P
      = .006), and a significant increase in oxygen saturation, oxygen saturation as
      measured by pulse oximetry 93.5% (90-98.5) vs 98.5% (95.5-100) (P = .0003). Use
      of HFNC significantly increased Pao(2) from 8.73 (7.13-11.13) to 15.27 (9.66
      25.6) kPa (P = .001) and moderately increased Paco(2), 5.26 (4.33-5.66) to 5.73
      (4.8-6.2) kPa (P = .005) without affecting pH. Median duration of HFNC was 26.5
      (17-121) hours. Six patients were secondarily intubated, and 3 died in the
      intensive care unit. CONCLUSION: Use of HFNC in patients with persistent ARF was
      associated with significant and sustained improvement of both clinical and
      biologic parameters.

PMID- 21958975
TI  - Emotional consequences of intensive care unit delirium and delusional memories
      after intensive care unit admission: a systematic review.
AB  - PURPOSE: The aim of this study was to review literature exploring the emotional
      consequences of delirium and delusional memories in intensive care unit patients.
      METHODS: A systematic review was performed using PubMed, Embase, Cumulative Index
      to Nursing and Allied Health Literature, and PsychINFO. RESULTS: Fourteen
      articles were eligible for this review. Five of them assessed delirium during
      intensive care unit admission, and the remainder assessed delusional memories
      during or after admission. No association was found for delirium and adverse
      emotional outcome. Data regarding delusional memories and emotional outcome were
      heterogenic. Some studies presented worse scores on posttraumatic stress disorder
      screening tools in patients with delusional memories, whereas other studies found
      better scores in patients with delirium or delusional memories. CONCLUSIONS:
      Based on current literature, no relationship could be shown for delirium and
      emotional outcome. Regarding delusional memories and adverse emotional outcome,
      results were in contradiction.

PMID- 21958976
TI  - Noninvasive ventilation with helium-oxygen in children.
AB  - Most existing literature on noninvasive ventilation (NIV) in combination with
      helium-oxygen (HELIOX) mixtures focuses on its use in adults, basically for
      treatment of acute exacerbations of chronic obstructive pulmonary disease. This
      article reviews and summarizes the theoretical basis, existing clinical evidence,
      and practical aspects of the use of NIV with HELIOX in children. There is only a
      small body of literature on HELIOX in pediatric NIV but with positive results.
      The reported experience focuses on treatment for patients with severe acute
      bronchiolitis who cannot be treated with standard therapies. The inert nature of
      helium adds no biological risk to NIV performance. Noninvasive ventilation with
      HELIOX is a promising therapeutic option for children with various respiratory
      pathologies who do not respond to conventional treatment. Further controlled
      studies should be warranted.

PMID- 21958977
TI  - Zinc supplementation in intensive care: results of a UK survey.
AB  - PURPOSE: Our laboratory receives many routine requests for plasma zinc analysis
      from intensive care units (ICUs) throughout Scotland. However, such requests are
      inappropriate because plasma zinc concentrations fall independently of
      nutritional deficiency during the systemic inflammatory response and, therefore,
      in critically ill patients. This survey was performed to investigate how
      widespread this practice was and if low plasma zinc concentrations were
      interpreted as zinc deficiency so triggering inappropriate initiation of zinc
      supplementation. MATERIALS AND METHODS: A questionnaire was sent to ICUs
      throughout the UK; nonresponders were contacted by telephone, and the
      questionnaire details were recorded. The questionnaire asked if plasma zinc was
      routinely requested, the frequency of requests, whether patients were
      supplemented with zinc, and if so, the grounds for supplementation and the dose
      given. RESULTS: Plasma measurement of zinc was routinely performed in 18% of UK
      ICUs. Zinc supplementation was given in 10%, usually as a result of finding low
      plasma zinc concentrations. Dosages of supplementation varied widely between
      ICUs: from 0.4 to 135 mg zinc per day. Approximately 6% of ICUs gave very high
      supplements of zinc of 90 and 135 mg/d. CONCLUSIONS: The finding of a low plasma
      zinc concentration in Intensive Therapy Unit patients is often misinterpreted as
      indicating zinc deficiency and inappropriately prompts zinc supplementation.
      There is no evidence base to support high-dose zinc supplementation in ICU
      patients. This practice is justifiable only if future randomized trials
      demonstrate a benefit.

PMID- 21958978
TI  - Lower serum endocan levels are associated with the development of acute lung
      injury after major trauma.
AB  - PURPOSE: Endocan is a proteoglycan expressed by endothelial cells in the lung
      that may inhibit leukocyte recruitment and thus prevent the development of acute
      lung injury (ALI). We tested the association of serum endocan levels with
      subsequent development of ALI after major trauma. MATERIALS AND METHODS: This was
      a single-center nested case-control study within a prospective cohort study of
      major trauma patients. Using an enzyme-linked immunosorbent assay test, we
      measured endocan levels from admission serum in 24 controls (no ALI) and 24 cases
      (ALI within 5 days of trauma). Multivariable logistic regression was used to test
      the association of admission serum endocan levels with subsequent ALI. RESULTS:
      Patients who developed ALI had lower levels of endocan on admission (mean, 3.5 +/
      1.4 ng/mL vs 4.9 +/- 2.6 ng/mL in controls; P = .02). For each 1-unit increase
      in serum endocan level, the odds ratio for ALI development decreased (0.69; 95%
      confidence interval, 0.49-0.97; P = .03). Lower endocan levels remained
      associated with a higher incidence of ALI after adjustment for age and illness
      severity. CONCLUSIONS: Lower levels of serum endocan on admission are associated
      with subsequent development of ALI in trauma patients. These observations may be
      explained by endocan-mediated blockade of leukocyte recruitment in the lung.

PMID- 21958979
TI  - Weaning predictors do not predict extubation failure in simple-to-wean patients.
AB  - BACKGROUND: Predictor indexes are often included in weaning protocols and may
      help the intensive care unit (ICU) staff to reach expected weaning outcome in
      patients on mechanical ventilation. OBJECTIVE: The objective of this study is to
      evaluate the potential of weaning predictors during extubation. DESIGN: This is a
      prospective clinical study. SETTINGS: The study was conducted in 3 medical
      surgical ICUs. PATIENTS: Five hundred consecutive unselected patients ventilated
      for more than 48 hours were included. METHODS AND MEASUREMENTS: All patients were
      extubated after 30 minutes of successful spontaneous breathing trial and followed
      up for 48 hours. The protocol evaluated hemodynamics, ventilation parameters,
      arterial blood gases, and the weaning indexes frequency to tidal volume ratio;
      compliance, respiratory rate, oxygenation, and pressure; maximal inspiratory
      pressure; maximal expiratory pressure; Pao(2)/fraction of inspired oxygen;
      respiratory frequency; and tidal volume during mechanical ventilation and in the
      1st and 30th minute of spontaneous breathing trial. RESULTS: Reintubation rate
      was 22.8%, and intensive care mortality was higher in the reintubation group (10%
      vs 31%; P < .0001). The areas under the receiver operating characteristic curve
      showed that tests did not discriminate which patients could tolerate extubation.
      CONCLUSION: Usual weaning indexes are poor predictors for extubation outcome in
      the overall ICU population.

PMID- 21958980
TI  - A window of opportunity for collaboration between intensivists and oncologists.

PMID- 21958981
TI  - Time spent in the emergency department and mortality rates in severely injured
      patients admitted to the intensive care unit: An observational study.
AB  - PURPOSE: The aim of this study was to identify the determinants of a shorter
      emergency department time (EDt) in patients with severe trauma (STPs) admitted to
      the intensive care unit and determine whether EDt influences mortality. PATIENTS
      AND METHODS: A prospective observational study of STPs (2005-2007) was conducted.
      With the variables available from the ED, 2 multiple logistic regression models
      (MLRM) were created: one for the factors associated with EDt less than or equal
      to median and the other with mortality. RESULTS: A total of 243 patients were
      included. The mean age was 43 years; 76% were male. The overall mortality rate
      was 20%. The median EDt was 120 minutes. The independent factors that were
      associated with the MLRM for an EDt of 120 minutes or less included age less than
      60 years, mechanical ventilation, severe traumatic brain injury, and a trauma and
      injury severity score of 20 or higher. The MLRM for mortality was age greater
      than 60 years, mechanical ventilation, traumatic brain injury and shock. An EDt
      of 120 minutes or less was associated with an increased risk of death in the
      univariate analysis but not in the MLRM. CONCLUSIONS: Patients in the ED with
      indicators of high trauma severity have a reduced EDt but a higher mortality
      rate. Advanced age increases both mortality and EDt. With the factors included in
      the model, EDt was not an independent factor for mortality in STPs.

PMID- 21958982
TI  - Comparison of 3 different methods used to measure the rapid shallow breathing
      index.
AB  - PURPOSE: Rapid shallow breathing index (RSBI) is conveniently measured through
      the ventilator. If continuous positive airway pressure (CPAP) is used, it may
      change the RSBI value. We measured the RSBI with a handheld spirometer and
      through the ventilator, with and without CPAP, to assess differences. MATERIALS
      AND METHODS: Rapid shallow breathing index was measured in 3 ways: (1) CPAP 0 cm
      H(2)O and fraction of inspired oxygen (Fio(2)) 0.4, (2) CPAP 5 cm H(2)O and
      Fio(2) 0.4, and (3) ventilator disconnected and Fio(2) 0.21. Tidal volume and
      respiratory frequency were recorded from ventilator monitor values in methods 1
      and 2, and from a handheld spirometer and observed respiratory frequency, in
      method 3. RESULTS: A total of 170 measurements, each using all 3 methods, were
      obtained from 80 patients admitted to a medical intensive care unit. The mean
      RSBI values for methods 1, 2, and 3 were 98.1 +/- 58.7, 87.6 +/- 51.2, and 108.3
      +/- 65.3, respectively (P < .001). The RSBI decreased by 9.4% when using CPAP 0
      cm H(2)O and by 19.1% when using CPAP 5 cm H(2)O. CONCLUSIONS: The RSBI values
      measured through the ventilator with CPAP 5 cm H(2)O are much lower than the
      values measured with a handheld spirometer. Even the RSBI values measured with
      CPAP 0 cm H(2)O are significantly lower. This is attributable to the base flow
      delivered by some ventilators. The difference must be taken into account during
      weaning assessment.

PMID- 21958983
TI  - Procalcitonin level as an aid for the diagnosis of bacterial infections following
      pediatric cardiac surgery.
AB  - PURPOSE: The aim of the present study was to determine if blood procalcitonin can
      serve as an aid to differentiate between bacterial and nonbacterial cause of
      fever in children after cardiac surgery. MATERIALS AND METHODS: A nested case
      control study of children who underwent open cardiac surgery in critical care
      units of fourth-level pediatric hospital was performed. Blood samples for
      procalcitonin level were collected 1 day before operation; 1 hour postoperation;
      on postoperative days 1, 2, and 5; and on the day of fever, when it occurred.
      RESULTS: Of 665 children who underwent cardiac bypass surgery, 126 had a febrile
      episode postoperatively, 47 children with a proven bacterial infection and 79
      without bacterial infection. Among the 68 children in whom fever developed within
      the first 5 postoperative days, procalcitonin level at fever day was
      significantly higher in those with bacterial infection (n = 16) than in those
      without infection (n = 52). Similarly, among the 58 children in whom fever
      developed after day 5 postoperation, a significant difference was found in
      procalcitonin level at fever day between those with (n = 31) and without (n = 27)
      bacterial infection. CONCLUSION: During the critical early and late periods after
      cardiac surgery in children, procalcitonin level may help to differentiate
      patients with bacterial infection from patients in whom the fever is secondary to
      nonbacterial infectious causes.

PMID- 21958984
TI  - Organizational and safety culture in Canadian intensive care units: relationship
      to size of intensive care unit and physician management model.
AB  - PURPOSE: The objectives of this study are to describe organizational and safety
      culture in Canadian intensive care units (ICUs), to correlate culture with the
      number of beds and physician management model in each ICU, and to correlate
      organizational culture and safety culture. MATERIALS AND METHODS: In this cross
      sectional study, surveys of organizational and safety culture were administered
      to 2374 clinical staff in 23 Canadian tertiary care and community ICUs. For the
      1285 completed surveys, scores were calculated for each of 34 domains. Average
      domain scores for each ICU were correlated with number of ICU beds and with
      intensivist vs nonintensivist management model. Domain scores for organizational
      culture were correlated with domain scores for safety culture. RESULTS: Culture
      domain scores were generally favorable in all ICUs. There were moderately strong
      positive correlations between number of ICU beds and perceived effectiveness at
      recruiting/retaining physicians (r = 0.58; P < .01), relative technical quality
      of care (r = 0.66; P < .01), and medical director budgeting authority (r = 0.46;
      P = .03), and moderately strong negative correlations with frequency of events
      reported (r = -0.46; P = .03), and teamwork across hospital units (r = -0.51; P =
      .01). There were similar patterns for relationships with intensivist management.
      For most pairs of domains, there were weak correlations between organizational
      and safety culture. CONCLUSION: Differences in perceptions between staff in
      larger and smaller ICUs highlight the importance of teamwork across units in
      larger ICUs.

PMID- 21958985
TI  - Exercise testing in survivors of intensive care--is there a role for
      cardiopulmonary exercise testing?
AB  - PURPOSE: The aims of this study were to assess the feasibility of cardiopulmonary
      exercise testing (CPET) for the early assessment of cardiorespiratory fitness in
      general adult intensive care unit (ICU) survivors and to characterize the
      pathophysiology of exercise limitation in this population. METHODS: Fifty general
      ICU survivors (ventilated for >= 5 days) performed a maximal cycle ergometer CPET
      within 6 weeks of hospital discharge. Health-related quality of life was measured
      by the Medical Outcome Study Short Form 36 version 2.0 questionnaire. RESULTS:
      Fifty patients (median age, 57 years; median Acute Physiology And Chronic Health
      Evaluation II score, 16) completed a CPET 24 +/- 14 days after hospital discharge
      with no adverse events. Significant exercise limitation was present with peak
      Vo(2) 56% +/- 16% predicted and anaerobic threshold (AT) 41% +/- 13% of peak
      predicted Vo(2). Prospectively stratified subgroup comparison showed that
      patients ventilated for 14 days or more had a significantly lower AT and peak
      Vo(2) than those ventilated for 5 to 14 days (AT: 9.6 vs 11.7 mL/kg per minute
      O(2), P = .009; peak Vo(2): 12.9 vs 15.3 mL/kg per minute O(2), P = .022). At
      peak exercise, heart rate reserve was 25% +/- 14%, breathing reserve was 47% +/-
      19%, and the respiratory exchange ratio was 0.96 +/- 0.11. Ventilatory
      equivalents for CO(2) (Eqco(2)) were 39 +/- 9. CONCLUSIONS: Significant exercise
      limitation is evident in patients who have had critical illness. Etiology of
      exercise limitation appears multifactorial, with general deconditioning and
      muscle weakness as major contributory factors. Early CPET appears a practical
      method of assessing exercise capacity in ICU survivors. Cardiopulmonary exercise
      testing could be used to select patients who may benefit most from a targeted
      physical rehabilitation program, aid in exercise prescription, and help assess
      the response to intervention.

PMID- 21958986
TI  - Biophysical and functional assays for viral membrane fusion peptides.
AB  - Membrane fusion is a protein catalyzed biophysical reaction that involves the
      simultaneous intermixing of two phospholipid bilayers and of the aqueous
      compartments bound by their respective bilayers. In the case of enveloped virus
      fusogens, short hydrophobic or amphipathic fusion peptides that are components of
      the larger fusion complex are essential for the membrane merger event. The
      process of cell-cell membrane fusion and syncytium formation induced by the
      nonenveloped fusogenic orthoreoviruses is driven by the Fusion-Associated Small
      Transmembrane (FAST) proteins, which are similarly dependent on the action of
      fusion peptides. In this article, we describe some simple methods for the
      biophysical characterization of viral membrane fusion peptides. Liposomes serve
      as an ideal model system for characterizing peptide-membrane interactions because
      their size, shape and composition can be readily manipulated. We present details
      of fluorescence assays used to elucidate the kinetics of membrane fusion as well
      as complimentary assays used to characterize peptide-induced liposome binding and
      aggregation.

PMID- 21958987
TI  - Rapid identification of recombinant Fabs that bind to membrane proteins.
AB  - Crystallographic studies of membrane proteins have been steadily increasing
      despite their unique physical properties that hinder crystal formation. Co
      crystallization with antibody fragments has emerged as a promising solution to
      obtain diffraction quality crystals. Antibody binding to the target membrane
      protein can yield a homogenous population of the protein. Interantibody
      interactions can also provide additional crystal contacts, which are minimized in
      membrane proteins due to micelle formation around the transmembrane segments.
      Rapid identification of antibody fragments that can recognize native protein
      structure makes phage display a valuable method for crystallographic studies of
      membrane proteins. Methods that speed the reliable characterization of phage
      display selected antibody fragments are needed to make the technology more
      generally applicable. In this report, a phage display biopanning procedure is
      described to identify Fragments antigen binding (Fabs) for membrane proteins. It
      is also demonstrated that Fabs can be rapidly grouped based on relative
      affinities using enzyme linked immunosorbent assay (ELISA) and unpurified Fabs.
      This procedure greatly speeds the prioritization of candidate binders to membrane
      proteins and will aid in subsequent structure determinations.

PMID- 21958989
TI  - Dosimetry in molecular nuclear therapy.
AB  - Advanced personalized dosimetry for molecular nuclear therapy has been shown to
      be feasible in clinical practice. At the same time instrumentation and dosimetric
      software are still evolving at a high pace. Procedures developed so far differ in
      approach and sophistication, and standard operating procedures necessary for
      accurate patient specific dosimetry do not yet exist. For this reason we
      restricted ourselves to reviewing the literature and highlighting relevant
      developments.

PMID- 21958988
TI  - New amphiphiles for membrane protein structural biology.
AB  - A challenging requirement for X-ray crystallography or NMR structure
      determination of membrane proteins (MPs), in contrast to soluble proteins, is the
      necessary use of amphiphiles to mimic the hydrophobic environment of membranes. A
      number of new detergents, lipids and non-detergent-like amphiphiles have been
      developed that stabilize MPs, and these have contributed to increased success in
      MP structural determinations in recent years. Despite some successes, currently
      available reagents are inadequate and there remains a pressing need for new
      amphiphiles. Literature examples and some new developments are selected here as a
      framework for discussing desirable properties of new amphiphiles for MP
      structural biology.

PMID- 21958990
TI  - Projection and patient satisfaction using the "Hamburger" nipple reconstruction
      technique.
AB  - Maintaining projection and achieving patient satisfaction are two key challenges
      in nipple reconstruction. Skin flap techniques such as CV and star flaps are
      currently favoured. The "Hamburger" technique was described in 2007 using stacked
      conchal cartilage discs within a skin flap construct, but no longer-term outcomes
      have been published. We evaluate both projection and patient satisfaction
      following nipple reconstruction using this technique. Twenty-three nipple
      reconstructions performed between 2007 and 2009 were reviewed. A standard pre
      tattooed cylinder skin pattern was used with 3 punch biopsies of conchal
      cartilage harvested through a post-auricular incision. At follow up,
      reconstructed nipples and donor sites were examined. Nipple projection was
      measured bilaterally. Patients completed a short questionnaire. Mean follow up
      was 24 months (9-31). Mean projection was 3.3 mm (range 0-5 mm) and was well
      matched to the contralateral nipple. No donor site keloid scarring was observed,
      however cartilage defects were easily palpable in all cases. Patients were
      satisfied or very satisfied with overall cosmesis in 91% of cases. They were
      satisfied or very satisfied with projection in 57% of cases. All patients found
      the donor site acceptable. With the "hamburger" technique medium-term projection
      was maintained in most cases and was comparable to published data for other
      techniques with or without cartilage. Patient satisfaction was high even when
      projection was not well maintained. This suggests that patient satisfaction and
      projection are not necessarily related. Donor site morbidity was low.

PMID- 21958991
TI  - Initial management of open tibial fractures in peripheral hospitals does not
      necessarily correlate with an increase in flap failure rates.

PMID- 21958992
TI  - [A statistical definition of aortic pulse wave velocity normality in a Portuguese
      population: a subanalysis of the EDIVA project].
AB  - INTRODUCTION: Aortic pulse wave velocity (PWV) has been associated with
      cardiovascular risk in different clinical subsets. This subanalysis of the EDIVA
      project aimed to establish criteria for normality of PWV based on a statistical
      definition that considers the fundamental physiological role of aging in arterial
      stiffness. METHODS: A sample of 668 healthy subjects (412 male) enrolled in the
      EDIVA Project (a prospective, multicenter, observational study) were studied.
      Mean age was 40.00 +/- 13.42 years, body mass index was 25.90 +/- 4.21kg/m(2),
      and systolic and diastolic blood pressure were respectively 125.47 +/- 11.18 and
      75.75 +/- 9.27mmHg. PWV was determined annually using a Complior device, and mean
      follow-up was 23.3 +/- 3.34 months. Personal and family history, physical
      examination, electrocardiogram and biochemical analysis were used to determine
      individual health. RESULTS: In the overall population PWV was 8.8 +/- 1.4m/sec,
      8.7 +/- 1.6m/sec in men and 8.9 +/- 1.5m/sec in women (p=NS). Normal PWV was
      defined as the 95th percentile adjusted for age and gender, above which PWV was
      considered abnormal. Serial evaluation of PWV also enabled the annual age
      dependent increase in PWV to be estimated at 5%, values above this cut-off being
      defined as abnormal vascular deterioration. CONCLUSION: This study establishes
      criteria for normality based on a statistical definition that takes into account
      the fundamental physiological role of aging in arterial stiffness. Additionally,
      it provides a cut-off for the clinical interpretation of serial PWV measurements.

PMID- 21958993
TI  - [Pulse wave velocity: a marker of arterial stiffness and its applicability in
      clinical practice].

PMID- 21958994
TI  - Family history of coronary heart disease, health care and health behaviors.
AB  - INTRODUCTION: Previous studies on health care and health behaviors in individuals
      with a family history of coronary heart disease (CHD) have produced contradictory
      results, and there is still no evidence that these individuals are more aware of
      their risk and have improved health behaviors and heath care. This study aims to
      evaluate health care and health behaviors according to family history of CHD.
      METHODS: Individuals randomly selected from the general population living in
      Porto, Portugal, aged >= 18 years (evaluation period: 1999-2003), and without
      prior history of chronic diseases (n=764), were evaluated by questionnaires on
      family and personal disease history, health care and health behaviors. A family
      history of CHD was defined as the occurrence of acute myocardial infarction or
      sudden death in at least one first-degree relative. Odds ratios and 95%
      confidence intervals (OR, 95% CI) were calculated using unconditional logistic
      regression after stratification for age (18-39 vs. >= 40 years) and education (<=
      6 vs. >6 years schooling). RESULTS: Among men, 20% reported a family history of
      CHD, approximately the same proportion as in women (19.4%) (p=0.900). The
      proportion of subjects with a family history of CHD was significantly higher in
      older (>= 40 vs. 18-39 years: 25.0% vs. 12.0%, p<0.001) and less educated
      individuals (>6 vs. <= 6 years: 27.0% vs. 17.1%, p=0.004). Overall, no
      significant associations were found between health care and behaviors and CHD
      family history. Only in younger individuals, after adjustment for education, was
      a significant positive association found between 1-2 dental visits and CHD family
      history (OR=2.92; 95% CI: 1.27-6.70). Younger subjects who smoked and consumed
      alcohol and caffeine also presented a higher probability of having CHD family
      history, but the associations were not statistically significant. DISCUSSION AND
      CONCLUSIONS: In this population without disease requiring regular medical care,
      individuals with CHD family history had similar care-seeking patterns and health
      behaviors to those without. These results suggest a lack of awareness of their
      increased risk and highlight the importance of developing measures to promote
      sustained and effective changes in risk factors in individuals with genetic
      susceptibility to CHD.

PMID- 21958995
TI  - [Thoracic fluid content - a possible determinant of ventilatory efficiency in
      patients with heart failure].
AB  - Ventilatory efficiency, evaluated by cardiopulmonary exercise testing (CPET), has
      considerable prognostic value in patients with chronic heart failure (CHF) due to
      left ventricular systolic dysfunction (LVSD). Its determinants nevertheless
      remain controversial. AIM: To investigate the possible correlation between
      parameters of ventilatory efficiency obtained by CPET and thoracic fluid content
      (TFC), assessed by thoracic electrical bioimpedance (TEB), in patients with CHF
      due to LVSD. METHODS: We studied 120 patients with LVSD and CHF, referred to our
      laboratory for CPET: 76% male, age 52.1 +/- 12.1 years, 37% of ischemic etiology,
      left ventricular ejection fraction 27.6 +/- 7.9%, 83% in sinus rhythm, 96%
      receiving ACEIs and/or ARBs and 79% beta-blockers, and 20% treated with a cardiac
      resynchronization device. TEB studies were performed after 15 minutes of rest,
      prior to symptom-limited treadmill CPET, using the modified Bruce protocol. CPET
      derived peak oxygen consumption (pVO(2)), the slope of the relationship between
      minute ventilation (VE) and carbon dioxide production (VCO(2)), VE/VCO(2) at the
      anaerobic threshold (AT), and TFC assessed by TEB were considered for analysis.
      RESULTS: TFC ranged between 20.6 and 45.8kOhm-1, mean 32.2, SD=5.7, median 32.7,
      pVO(2) 8.9-40.6 ml/kg/min, mean 21.0, SD 6.2, median 20.2, VE/VCO(2) slope 19.8
      60.7, mean 30.7, SD 7.9, median 29.1 and VE/VCO(2) at AT 21-62, mean 33.1, SD
      7.5, median 31.5. By linear regression, TFC did not correlate with pVO(2)
      (r=0.05, p=0.58), but showed correlation with parameters of ventilatory
      efficiency: r=0.20, p=0.032, r(2)=0.04 for VE/VCO(2) slope and r=0.25, p=0.009,
      r(2)=0.06 for VE/VCO(2) at AT. CONCLUSION: TFC correlates with CPET parameters of
      ventilatory efficiency in patients with CHF due to LVSD, suggesting that it may
      be one of its determinants.

PMID- 21958996
TI  - [Multislice computed tomography in the selection of candidates for transcatheter
      aortic valve implantation].
AB  - Transcatheter aortic valve implantation is an emerging treatment option for
      severe symptomatic aortic stenosis in patients considered unsuitable for surgical
      valve replacement. The authors review the use of multislice computed tomography
      in the selection of candidates for transcatheter aortic valve replacement,
      procedural support and post-interventional follow-up. A single-center experience
      of the role of this imaging technique is also described. Multislice computed
      tomography is an essential imaging tool in the selection and exclusion of
      candidates for transcatheter aortic valve implantation, providing evaluation of
      coronary anatomy and the relationship of the coronary ostia with the aortic valve
      structure, and accurate analysis of the valve annulus and aortic root, left
      ventricular outflow tract, aorta and peripheral vascular access routes.
      Multislice computed tomography is also central to the choice of appropriate
      prosthesis size. In addition, it guides arterial puncture by image fusion
      techniques and enables correct prosthesis apposition to be verified. This review
      aims to describe the role of computed tomography in this increasingly common
      interventional valve procedure, providing an overview of current knowledge and
      applications.

PMID- 21958997
TI  - Arterial thrombosis and acute myocardial infarction with angiographically normal
      coronary arteries in a woman heterozygous for both factor V Leiden and
      prothrombin mutation.
AB  - Thirteen years after her last thrombotic event, anticoagulation was discontinued
      in a patient with combined thrombophilia involving mutation in factor V and
      G20210A polymorphism of the prothrombin gene. The only history was of arterial
      thrombosis. Three months later she presented a transmural myocardial infarction
      caused by coronary thrombosis.

PMID- 21958998
TI  - [Cardiac injury in the context of metastatic hepatocellular carcinoma].
AB  - Hepatocellular carcinoma with extension or metastasis to the right atrium is an
      uncommon form of cardiac malignancy. The authors report the case of a 51-year-old
      patient with hepatocellular carcinoma and thrombi in the portal and mesenteric
      veins, which histopathology revealed to be metastatic. Echocardiography showed a
      right atrial mass which in this context has to be considered as a possible
      cardiac metastasis.

PMID- 21958999
TI  - [Images in cardiology after clinical observation - aortic dissection in Marfan
      syndrome].
AB  - INTRODUCTION: Stanford type A aortic dissection is a rare phenomenon with high
      short-term mortality and clinical manifestations that can make differential
      diagnosis a lengthy process requiring several diagnostic examinations.
      OBJECTIVES: Based on a case report, the aim is to highlight the importance of
      physical examination in the initial management of these patients and of rapid
      access to a surgical center. A brief review follows on the diagnosis and
      treatment of ascending aortic dissection, and its specific nature in Marfan
      syndrome. CASE REPORT: A 33-year-old man was admitted to the emergency department
      of a district hospital with chest and back pain associated with vomiting, 20
      hours after symptom onset. Initial physical examination revealed an aortic
      systolic murmur and musculoskeletal morphological abnormalities compatible with
      Marfan syndrome. Given suspected aortic dissection, a transthoracic
      echocardiogram was immediately performed, which showed an extensive intimal flap
      originating at the sinotubular junction. He was transferred to the cardiothoracic
      surgery department of a referral hospital where he was treated by a Bentall
      procedure. CONCLUSION: In this case, careful physical examination during initial
      assessment raised the suspicion that this patient was in a high-risk group for
      aortic dissection, thus avoiding unnecessary and lengthy exams. This diagnosis
      requires emergent surgical treatment, and so direct contact in real time between
      those making in the diagnosis and the surgeon is essential, as well as protocols
      governing immediate access to a surgical center.

PMID- 21959000
TI  - Idiopathic biatrial dilatation characterized by multimodality imaging.

PMID- 21959001
TI  - Aortocoronary dissection complicating percutaneous angioplasty.

PMID- 21959002
TI  - [Can differences in corrected coronary opacification measured with computed
      tomography predict resting coronary artery flow?].
AB  - OBJECTIVES: A proof-of-concept study was undertaken to determine whether
      differences in corrected coronary opacification (CCO) within coronary lumen can
      identify arteries with abnormal resting coronary flow. BACKGROUND: Although
      computed tomographic coronary angiography can be used for the detection of
      obstructive coronary artery disease, it cannot reliably differentiate between
      anatomical and functional stenoses. METHODS: Computed tomographic coronary
      angiography patients (without history of revascularization, cardiac
      transplantation, and congenital heart disease) who underwent invasive coronary
      angiography were enrolled. Attenuation values of coronary lumen were measured
      before and after stenoses and normalized to the aorta. Changes in CCO were
      calculated, and CCO differences were compared with severity of coronary stenosis
      and Thrombolysis In Myocardial Infarction (TIMI) flow at the time of invasive
      coronary angiography. RESULTS: One hundred four coronary arteries (n=52, mean
      age=60.0+/-9.5 years; men=71.2%) were assessed. Compared with normal arteries,
      the CCO differences were greater in arteries with computed tomographic coronary
      angiography diameter stenoses >=50%. Similarly, CCO differences were greater in
      arteries with TIMI flow grade <3 (0.406+/-0.226) compared with those with normal
      flow (TIMI flow grade 3) (0.078+/-0.078, p<0.001). With CCO differences, abnormal
      coronary flow (TIMI flow grade<3) was identified with a sensitivity and
      specificity, positive predictive value, and negative predictive value of 83.3%
      (95% confidence interval [CI]: 57.7 to 95.6%), 91.2% (95% CI: 75.2% to 97.7%),
      83.3% (95% CI: 57.7% to 95.6%), and 91.2% (95% CI: 75.2% to 97.7%), respectively.
      Accuracy of this method was 88.5% with very good agreement (kappa=0.75, 95% CI:
      0.55 to 0.94). CONCLUSIONS: Changes in CCO across coronary stenoses seem to
      predict abnormal (TIMI flow grade<3) resting coronary blood flow. Further studies
      are needed to understand its incremental diagnostic value and its potential to
      measure stress coronary blood flow.

PMID- 21959003
TI  - Penile duplication: is it necessary to excise one of the penises?
AB  - A 37-day-old boy presented with a duplicated penis. Examination revealed presence
      of two penises, one dorsally located and one ventrally, a large left inguinal
      hernia and absent right thumb. Abdominal ultrasound and micturating
      cystourethrogram showed normal kidneys, a single urinary bladder, and partial
      urethral duplication with no vesicoureteric reflux. The patient was subjected to
      a new technique, reconstructing the penis without removal of corporal tissue, and
      therefore not compromising its size. A satisfactory result was achieved. The case
      is being reported due to its rarity and different surgical approach, in contrast
      to previous reports of management of diphallia involving excision of one of the
      penises.

PMID- 21959004
TI  - Dermis isolated adult stem cells for cartilage tissue engineering.
AB  - Adult stem cells from the dermal layer of skin are an attractive alternative to
      primary cells for meniscus engineering, as they may be easily obtained and used
      autologously. Recently, chondroinducible dermis cells from caprine skin have
      shown promising characteristics for cartilage tissue engineering. In this study,
      their multilineage differentiation capacity is determined, and methods of
      expanding and tissue engineering these cells are investigated. It was found that
      these cells could differentiate along adipogenic, osteogenic, and chondrogenic
      lineages, allowing them to be termed dermis isolated adult stem cells (DIAS
      cells). Focusing on cartilage tissue engineering, it was found that passaging
      these cells in chondrogenic medium and forming them into self-assembled tissue
      engineered constructs caused upregulation of collagen type II and COMP gene
      expression. Further investigation showed that applying transforming growth factor
      beta1 (TGF-beta1) or bone morphogenetic protein 2 (BMP-2) to DIAS constructs
      caused increased sulfated glycosaminoglycan content. Additionally, TGF-beta1
      treatment caused significant increases in compressive properties and construct
      contraction. In contrast, BMP-2 treatment resulted in the largest constructs, but
      did not increase compressive properties. These results show that DIAS cells can
      be easily manipulated for cartilage tissue engineering strategies, and may also
      be a useful cell source for other mesenchymal tissues.

PMID- 21959005
TI  - Extrahepatic islet transplantation with microporous polymer scaffolds in
      syngeneic mouse and allogeneic porcine models.
AB  - Intraportal transplantation of islets has successfully treated select patients
      with type 1 diabetes. However, intravascular infusion and the intrahepatic site
      contribute to significant early and late islet loss, yet a clinical alternative
      has remained elusive. We investigated non-encapsulating, porous, biodegradable
      polymer scaffolds as a vehicle for islet transplantation into extrahepatic sites,
      using syngeneic mouse and allogeneic porcine models. Scaffold architecture was
      modified to enhance cell infiltration leading to revascularization of the islets
      with minimal inflammatory response. In the diabetic mouse model, 125 islets
      seeded on scaffolds implanted into the epididymal fat pad restored normoglycemia
      within an average of 1.95 days and transplantation of only 75 islets required
      12.1 days. Increasing the pore size to increase islet-islet interactions did not
      significantly impact islet function. The porcine model was used to investigate
      early islet engraftment. Increasing the islet seeding density led to a greater
      mass of engrafted islets, though the efficiency of islet survival decreased.
      Transplantation into the porcine omentum provided greater islet engraftment than
      the gastric submucosa. These results demonstrate scaffolds support murine islet
      transplantation with high efficiency, and feasibility studies in large animals
      support continued pre-clinical studies with scaffolds as a platform to control
      the transplant microenvironment.

PMID- 21959006
TI  - A paclitaxel-conjugated adenovirus vector for targeted drug delivery for tumor
      therapy.
AB  - Tumor-targeted drug delivery is an attractive strategy in cancer treatment. Our
      previous study demonstrated that modified adenovirus has strong tumor targeting
      ability and less toxicity to surrounding normal tissue. In this study, Paclitaxel
      (PTX), a widely used clinical anticancer drug, was conjugated to folate-modified
      adenovirus (Ad) nanoparticles by using succinic anhydride and Fmoc-Glu(OtBu)-OH
      linkers to form two prodrugs, FA-Ad-Suc-PTX and FA-Ad-ICG02-Glu-PTX. Near
      infrared (NIR) fluorescent dye ICG-Der-02 was attached to -NH(2)-Glu(OtBu)-PTX
      for in vivo optical imaging. In vitro and acute toxicity study demonstrates the
      low toxicity of the prodrug FA-Ad-Suc-PTX and FA-Ad-ICG02-Glu-PTX compared to the
      free drug. The dynamic behaviors and targeting ability of FA-Ad-ICG02-Glu-PTX on
      MDA-MB-231 tumor-bearing mice were investigated by NIR fluorescence imaging. The
      result show that PTX-conjugated Ad vector could enhance the targeting and
      residence time in tumor site. In vitro and in vivo studies demonstrate that
      Coxsackie adenovirus receptor (CAR) or foliate receptor (FR)-mediated uptake of
      FA-Ad-loaded PTX induced highly anti-tumor activity. The results support the
      potential of using chemically modified Ad vector as drug-loaded tumor-targeting
      delivery system.

PMID- 21959007
TI  - Nanoprobes for in vitro diagnostics of cancer and infectious diseases.
AB  - The successful and explosive development of nanotechnology is significantly
      impacting the fields of biology and medicine. Among the spectacular developments
      of nanobiotechnology, interest has grown in the use of nanomaterials as
      nanoprobes for bioanalysis and diagnosis. Herein, we review state-of-the-art
      nanomaterial-based probes and discuss their applications in in vitro diagnostics
      (IVD) and challenges in bringing these fields together. Major classes of
      nanoprobes include quantum dots (QDs), plasmonic nanoparticles, magnetic
      nanoparticles, nanotubes, nanowires, and multifunctional nanomaterials. With the
      advantages of high volume/surface ratio, surface tailorability,
      multifunctionality, and intrinsic properties, nanoprobes have tremendous
      applications in the areas of biomarker discovery, diagnostics of infectious
      diseases, and cancer detection. The distinguishing features of nanoprobes for in
      vitro use, such as harmlessness, ultrasensitivity, multiplicity, and point-of
      care use, will bring a bright future of nanodiagnosis.

PMID- 21959009
TI  - Lysostaphin-functionalized cellulose fibers with antistaphylococcal activity for
      wound healing applications.
AB  - With the emergence of "super bacteria" that are resistant to antibiotics, e.g.,
      methicillin-resistant Staphylococcus aureus, novel antimicrobial therapies are
      needed to prevent associated hospitalizations and deaths. Bacteriophages and
      bacteria use cell lytic enzymes to kill host or competing bacteria, respectively,
      in natural environments. Taking inspiration from nature, we have employed a cell
      lytic enzyme, lysostaphin (Lst), with specific bactericidal activity against S.
      aureus, to generate anti-infective bandages. Lst was immobilized onto
      biocompatible fibers generated by electrospinning homogeneous solutions of
      cellulose, cellulose-chitosan, and cellulose-poly(methylmethacrylate) (PMMA) from
      1-ethyl-3-methylimidazolium acetate ([EMIM][OAc]), room temperature ionic liquid.
      Electron microscopic analysis shows that these fibers have submicron-scale
      diameter. The fibers were chemically treated to generate aldehyde groups for the
      covalent immobilization of Lst. The resulting Lst-functionalized cellulose fibers
      were processed to obtain bandage preparations that showed activity against S.
      aureus in an in vitro skin model with low toxicity toward keratinocytes,
      suggesting good biocompatibility for these materials as antimicrobial matrices in
      wound healing applications.

PMID- 21959008
TI  - The transduction of Coxsackie and Adenovirus Receptor-negative cells and
      protection against neutralizing antibodies by HPMA-co-oligolysine copolymer
      coated adenovirus.
AB  - Adenoviral (AdV) gene vectors offer efficient nucleic acid transfer into both
      dividing and non-dividing cells. However issues such as vector immunogenicity,
      toxicity and restricted transduction to receptor-expressing cells have prevented
      broad clinical translation of these constructs. To address this issue, engineered
      AdV have been prepared by both genetic and chemical manipulation. In this work, a
      polymer-coated Ad5 formulation is optimized by evaluating a series of N-(2
      hydroxypropyl) methacrylamide (HPMA)-co-oligolysine copolymers synthesized by
      living polymerization techniques. This synthesis approach was used to generate
      highly controlled and well-defined polymers with varying peptide length (K(5),
      K(10) and K(15)), polymer molecular weight, and degradability to coat the viral
      capsid. The optimal formulation was not affected by the presence of serum during
      transduction and significantly increased Ad5 transduction of several cell types
      that lack the Coxsackie and Adenovirus Receptor (CAR) by up to 6-fold compared to
      unmodified AdV. Polymer-coated Ad5 also retained high transduction capability in
      the presence of Ad5 neutralizing antibodies. The critical role of heparan sulfate
      proteoglycans (HSPGs) in mediating cell binding and internalization of polymer
      coated AdV was also demonstrated by evaluating transduction in HSPG-defective
      recombinant CHO cells. The formulations developed here are attractive vectors for
      ex vivo gene transfer in applications such as cell therapy. In addition, this
      platform for adenoviral modification allows for facile introduction of
      alternative targeting ligands.

PMID- 21959010
TI  - The creation of an in vitro adipose tissue that contains a vascular-adipocyte
      complex.
AB  - An increased demand for soft-tissue substitutes has impelled the development of
      an in vitro adipose tissue. Ideally, such a tissue should contain a vascular
      network that can deliver blood throughout the construct following its
      engraftment. This study describes the in vitro fabrication of a pre-vascularized
      adipose tissue entirely using a self-assembly approach. Adult human adipose
      stromal cells (ASCs) provided the foundation for this construct. These cells were
      cultured at high density in the presence of elevated levels of ascorbate prior to
      adipocytic induction. Vascular support cells consisting of dermal fibroblasts,
      mixtures of adipose stromal cells and bone marrow mesenchymal stem cells (MSCs)
      were introduced to sustain an extensive vascular network formed by human
      umbilical vein endothelial cells (HUVECs). MSCs were introduced to serve as
      perivascular cells. The resulting construct contained a vascular-adipose tissue
      continuum that was held together by basement membrane molecules. This construct
      contains multiple cell types that are typically found in adipose tissue:
      adipocytes, pre-adipocytes, stem cells, fibroblasts, vascular cells, and
      perivascular support cells. As such, these constructs can be employed both for in
      vitro studies to assay cellular interactions between vasculature and other
      components of adipose tissue. Further, they can also be engrafted into athymic
      hosts to study vascular and adipocyte stability.

PMID- 21959011
TI  - Accelerated gene transfer through a polysorbitol-based transporter mechanism.
AB  - Here we report an accelerated gene transfer through a polysorbitol-based
      osmotically active transporter (PSOAT) that shows several surprising results
      through interesting mechanisms. The nano-sized and well-complexed PSOAT/DNA
      particles are less toxic, stable at serum and show no aggregation after
      lyophilization due to their polysorbitol backbone. The transfection is remarkably
      accelerated both in vitro and in vivo, presumably due to a transporter mechanism
      of PSOAT in spite of possibility of reduction of transfection by many hydroxyl
      groups in the transporter. PSOAT possesses a transporter mechanism owing to its
      polysorbitol backbone, which enhances cellular uptake by exerting polysorbitol
      transporter activity, thus accelerates gene transfer to cells because
      transfection ability of PSOAT is drastically reduced in the presence of a
      cyclooxygenase (COX)-2-specific inhibitor, which we have reported as an inhibitor
      of the transporter to cells. Moreover, the gene expression is found to be
      enhanced by hyperosmotic activity and buffering capacity due to polysorbitol and
      polyethylenimine backbone of PSOAT, respectively. The polysorbitol in PSOAT
      having polyvalency showed more efficiency in accelerating gene transfer
      capability than monovalent sorbitol. The above interesting mechanisms display
      PSOAT as a remarkably potential system to deliver therapeutic (small interfering
      RNA) and diagnostic agents for effective treatment of cancer.

PMID- 21959012
TI  - Achromobacter xylosoxidans mesh related infection: a case of delayed diagnosis
      and management.
AB  - We present the first case of mesh related infection caused by Achromobacter
      xylosoxidans after ventral hernia repair. After repair of a small paraumbilical
      hernia, the postoperative course was complicated by persistent discharging
      sinuses despite the removal of underlying polypropylene mesh. Removal of an
      intrabdominal omental inflammatory mass containing pus that showed growth of A.
      xylosoxidans led to the resolution of all the symptoms.

PMID- 21959013
TI  - A new type of ureteral stent will facilitate stent removal.

PMID- 21959014
TI  - Introduction of new atrial fibrillation ablation technology into clinical
      practice: the cart before the horse?

PMID- 21959015
TI  - Expanding the role of statins in postoperative atrial fibrillation.

PMID- 21959016
TI  - Regulation of the p38 mitogen-activated protein kinase and dual-specificity
      phosphatase 1 feedback loop modulates the induction of interleukin 6 and 8 in
      cells infected with coronavirus infectious bronchitis virus.
AB  - Induction of pro-inflammatory response is a crucial cellular process that detects
      and controls the invading viruses at early stages of the infection. Along with
      other innate immunity, this nonspecific response would either clear the invading
      viruses or allow the adaptive immune system to establish an effective antiviral
      response at late stages of the infection. The objective of this study was to
      characterize cellular mechanisms exploited by coronavirus infectious bronchitis
      virus (IBV) to regulate the induction of two pro-inflammatory cytokines,
      interleukin (IL)-6 and IL-8, at the transcriptional level. The results showed
      that IBV infection of cultured human and animal cells activated the p38 mitogen
      activated protein kinase (MAPK) pathway and induced the expression of IL-6 and IL
      8. Meanwhile, IBV has developed a strategy to counteract the induction of IL-6
      and IL-8 by inducing the expression of dual-specificity phosphatase 1 (DUSP1), a
      negative regulator of the p38 MAPK, in order to limit the production of an
      excessive amount of IL-6 and IL-8 in the infected cells. As activation of the p38
      MAPK pathway and induction of IL-6 and IL-8 may have multiple pathogenic effects
      on the whole host as well as on individual infected cells, regulation of the p38
      MAPK and DUSP1 feedback loop by IBV may modulate the pathogenesis of the virus.

PMID- 21959017
TI  - A small nonhuman primate model for filovirus-induced disease.
AB  - Ebolavirus and Marburgvirus are members of the filovirus family and induce a
      fatal hemorrhagic disease in humans and nonhuman primates with 90% case fatality.
      To develop a small nonhuman primate model for filovirus disease, common marmosets
      (Callithrix jacchus) were intramuscularly inoculated with wild type Marburgvirus
      Musoke or Ebolavirus Zaire. The infection resulted in a systemic fatal disease
      with clinical and morphological features closely resembling human infection.
      Animals experienced weight loss, fever, high virus titers in tissue,
      thrombocytopenia, neutrophilia, high liver transaminases and phosphatases and
      disseminated intravascular coagulation. Evidence of a severe disseminated viral
      infection characterized principally by multifocal to coalescing hepatic necrosis
      was seen in EBOV animals. MARV-infected animals displayed only moderate fibrin
      deposition in the spleen. Lymphoid necrosis and lymphocytic depletion observed in
      spleen. These findings provide support for the use of the common marmoset as a
      small nonhuman primate model for filovirus induced hemorrhagic fever.

PMID- 21959021
TI  - Over expression of IL-10 by macrophages overcomes resistance to murine
      filariasis.
AB  - Individuals infected with parasitic helminths are able to tolerate the presence
      of parasites for considerable time without clinical pathology. Immunosuppressive
      responses induced by the filarial parasite are considered responsible for this
      long-lasting relationship, inuring to the benefit of both parasite and host. In
      order to directly link IL-10 with parasite survival, we infected mice, in which
      over expression of IL-10 was restricted to macrophages under control of the CD68
      promoter (macIL-10tg), with Litomosoides sigmodontis. IL-10 overexpression by
      macrophages led to increased susceptibility with a significantly higher number of
      adult worms. Most profound, IL-10 overexpression was sufficient to convert
      resistant FVB wild-type mice towards a patent phenotype, since microfilariae were
      exclusively found in macIL-10tg mice. These findings were associated with reduced
      Th2 cytokine production in macIL-10tg mice. Expression of arginase-1, Ym1 and
      Fizz1, genes that are found strongly expressed in murine alternatively activated
      macrophages, were detected in macIL-10tg mice. Thus, IL-10 produced by
      macrophages with characteristics of alternative activation can overcome
      resistance and allow full patency in murine filariasis.

PMID- 21959018
TI  - Noise and crosstalk in two quorum-sensing inputs of Vibrio fischeri.
AB  - BACKGROUND: One of the puzzles in bacterial quorum sensing is understanding how
      an organism integrates the information gained from multiple input signals. The
      marine bacterium Vibrio fischeri regulates its bioluminescence through a quorum
      sensing mechanism that receives input from three pheromone signals, including two
      acyl homoserine lactone (HSL) signals. While the role of the 3-oxo-C6 homoserine
      lactone (3OC6HSL) signal in activating the lux genes has been extensively studied
      and modeled, the role of the C8 homoserine lactone (C8HSL) is less obvious, as it
      can either activate luminescence or block its activation. It remains unclear how
      crosstalk between C8HSL and 3OC6HSL affects the information that the bacterium
      obtains through quorum sensing. RESULTS: We have used microfluidic methods to
      measure the response of individual V.fischeri cells to combinations of C8HSL and
      3OC6HSL. By measuring the fluorescence of individual V.fischeri cells containing
      a chromosomal gfp-reporter for the lux genes, we study how combinations of
      exogenous HSLs affect both the population average and the cell-to-cell
      variability of lux activation levels. At the level of a population average, the
      crosstalk between the C8HSL and 3OC6HSL inputs is well-described by a competitive
      inhibition model. At the level of individual cells, the heterogeneity in the lux
      response depends only on the average degree of activation, so that the noise in
      the output is not reduced by the presence of the second HSL signal. Overall we
      find that the mutual information between the signal inputs and the lux output is
      less than one bit. A nonlinear correlation between fluorescence and
      bioluminescence outputs from lux leads to different noise properties for these
      reporters. CONCLUSIONS: The lux genes in V.fischeri do not appear to distinguish
      between the two HSL inputs, and even with two signal inputs the regulation of lux
      is extremely noisy. Hence the role of crosstalk from the C8HSL input may not be
      to improve sensing precision, but rather to suppress the sensitivity of the
      switch for as long as possible during colony growth.

PMID- 21959022
TI  - Minireview: the role of the vacuolar ATPase in nematodes.
AB  - The vacuolar ATPase enzyme complex (V-ATPase) pumps protons across membranes,
      energised by hydrolysis of ATP. It is involved in many physiological processes
      and has been implicated in many different diseases. While the broader functions
      of V-ATPases have been reviewed extensively, the role of this complex in
      nematodes specifically has not. Here, the essential role of the V-ATPase in
      nematode nutrition, osmoregulation, synthesis of the cuticle, neurobiology and
      reproduction is discussed. Based on the requirement of V-ATPase activity, or
      components of the V-ATPase, for these processes, the potential of the V-ATPase as
      a drug target for nematode parasites, which cause a significant burden to human
      health and agriculture, is also discussed. The V-ATPase has all the
      characteristics of a suitable drug target against nematodes, however the
      challenge will be to develop a high-throughput assay with which to test potential
      inhibitors.

PMID- 21959023
TI  - Human infections of fish-borne trematodes in Vietnam: prevalence and molecular
      specific identification at an endemic commune in Nam Dinh province.
AB  - The prevalence of fish-borne trematodes in humans and their molecular
      identification was investigated in the Rang Dong commune of Nam Dinh province,
      Vietnam, between January 2009 and December 2010. A total of 405 people in this
      commune were interviewed on the habit of eating raw fish and all of their stool
      samples were collected using the Kato-Katz technique for examination of the
      presence of fish-borne trematodes. The worms (and eggs) were first
      morphologically examined, counted, described and identified, then the
      representative isolates were subjected for molecular species confirmation. A
      total of 385 adult flukes collected from 10 patients were morphologically
      identified to species and defined as Clonorchis sinensis (14.58%) in
      Opisthorchiidae family, Haplorchis taichui (32.29%), Haplorchis pumilio (52.08%)
      and Centrocestus formosanus (1.04%) in Heterophyidae family. A high rate (77.8%)
      of the interviewees was found to have the habit of eating raw fish. This habit
      was attributed to the high infection rate of fish-borne trematode in humans
      (22.72%; OR=2.486). The infection rate of fish-borne trematodes in males was
      higher (29.3%) than that in females (16.0%) and increased by age, reaching the
      highest in the patients aged 40-59 years (28.2-28.7%). The infection intensity of
      fish-borne trematode was found light (336 EPG). Adult flukes were collected from
      a group of the patients with the highest intensity of infection and subjected to
      molecular and phylogenetic analysis using a portion (326 bp) of mitochondrial
      cox1. Phylogenetic tree inferred from cox1 sequences using sequence data for 34
      isolates of opisthorchid, heterophyid, fasciolid, paragonimid, schistosomid
      trematodes and taeniid cestodes revealed that they are distinct groups. The newly
      collected with the known clonorchid and heterophyid isolates form the well
      defined taxonomic groups, respectively, confirming that C. sinensis and
      Haplorchis spp. (H. pumilio and H. taichui) were among the collected samples.

PMID- 21959024
TI  - Procalcitonin measurements for guiding antibiotic treatment in pediatric
      pneumonia.
AB  - In order to evaluate the use of an algorithm based on a procalcitonin (PCT) cut
      off value as a means of guiding antibiotic therapy, 319 hospitalised children
      with uncomplicated community-acquired pneumonia (CAP) were randomised 1:1 to be
      treated on the basis of the algorithm or in accordance with standard guidelines.
      The children in the PCT group did not receive antibiotics if their PCT level upon
      admission was <0.25 ng/mL, and those receiving antibiotics from the time of
      admission were treated until their PCT level was >= 0.25 ng/mL. The final
      analysis was based on 155 patients in the PCT group and 155 in the control group.
      In comparison with the controls, the PCT group received significantly fewer
      antibiotic prescriptions (85.8% vs 100%; p < 0.05), were exposed to antibiotics
      for a shorter time (5.37 vs 10.96 days; p < 0.05), and experienced fewer
      antibiotic-related adverse events (3.9% vs 25.2%; p < 0.05), regardless of CAP
      severity. There was no significant between-group difference in recurrence of
      respiratory symptoms and new antibiotic prescription in the month following
      enrollment. The results of this first prospective study using a PCT cut-off value
      to guide antibiotic therapy for pediatric CAP showed that this approach can
      significantly reduce antibiotic use and antibiotic-related adverse events in
      children with uncomplicated disease. However, because the study included mainly
      children with mild to moderate CAP and the risk of the use of the algorithm-based
      approach was not validated in a relevant number of severe cases, further studies
      are needed before it can be used in routine clinical practice.

PMID- 21959025
TI  - An overview of evidence-based mental health.

PMID- 21959026
TI  - Evidence-based medicine: opportunities and challenges in a diverse society.
AB  - In this article we explore the discourse and practice of evidence-based medicine
      (EBM) in the context of social and cultural diversity. The article consists of 2
      parts. First, we begin by defining EBM, describing its historical development and
      current ascendance in medical practice. We then note its importance in
      contemporary psychiatry, comparing dynamics between the United States and Canada.
      Secondly, we offer a constructive critique of the application of EBM and evidence
      based practices in the context of ethnocultural diversity, as one consistent
      reflection on the EBM literature is that it is does not adequately address issues
      of diversity. In doing so, we use the situation here in Canada as an extended
      case study, though our observations will likely be applicable in other diverse
      nations, such as the United States, the United Kingdom, and Australia. We
      critically examine the following 6 issues related to the practice of EBM in a
      diverse society: generalizability and transferability of evidence-based
      interventions; diversifying standards of evidence in EBM; strategies to address
      diversity in EBM research; cultural adaptations of evidence-based interventions;
      integrating idiographic knowledge; and, training and health service delivery.
      Concurrent with our critique, we offer research and practice suggestions that may
      address outstanding challenges vis-a-vis the practice of EBM in a diverse
      society. These include a need for more effectiveness research, more openness to
      diverse sources of knowledge, better integration of idiographic and nomothetic
      knowledge, and a critical approach to extrapolation and transfer of knowledge.

PMID- 21959027
TI  - Economic approaches to improving access to evidence-based and recovery-oriented
      services for people with severe mental illness.
AB  - During the past 3 decades, research has identified several psychosocial evidence
      based practices (EBPs) for people with severe mental illness (SMI). Starting from
      a different origin, the recovery movement has influenced perceptions of how EBPs
      and other services should be delivered, and also emphasized the value of peer
      supports. We now know much more than 30 years ago about the kinds of services
      that help people with SMI live satisfying lives in the community. Evidence-based
      and recovery-oriented services require additional resources but use them
      sparingly: they are highly individualized, often result in reductions in costs of
      other mental health services, such as hospitalizations, and favour reliance on
      and integration into community settings rather than mental health services.
      Nevertheless, access to such services remains very limited. During the same
      period, the place of medications in the services system has become a source of
      growing concern, and there are several reasons to believe that current spending
      on medications is excessive. Inadequate housing and community supports that
      increase lengths of stay unnecessarily and spending on ineffective, nonrecovery
      oriented vocational services are only 2 additional forms of misallocation of
      resources. Devolving control over medication budgets to regional or local health
      authorities, introducing program budgeting and marginal analysis, and
      implementing individual budgets to give more control to service users (in
      addition to promoting shared decision making) merit further investigation as
      potential strategies to improve outcomes for people with SMI in Canada in the
      context of limited budgets.

PMID- 21959028
TI  - A (re)-evaluation of the symptom structure of borderline personality disorder.
AB  - OBJECTIVE: Despite evidence of significant symptom heterogeneity and excessive
      diagnostic comorbidity, many contend that borderline personality disorder (BPD)
      is unidimensional, an assumption that rests primarily on results from factor
      analytic investigations of BPD symptom criteria. We note several limitations in
      the literature and argue that the symptom structure of BPD can be best clarified
      by using both factor analytic techniques and examining the BPD symptom dimensions
      in relation to external criteria (that is, personality traits). Our goals were
      to: examine if the symptoms of BPD are best conceptualized as unidimensional or
      multidimensional, and determine the extent to which personality traits account
      for any symptom dimensions that underlie BPD. METHOD: All published structural
      models of the BPD symptom criteria were identified and tested for statistical fit
      using confirmatory factor analysis in a sample of 373 patients who had completed
      the Structured Clinical Interview for the Diagnostic and Statistical Manual of
      Mental Disorders-Axis II Personality Questionnaire BPD scale. Dimensions from the
      best fitting model were examined in relation to traits from the Five-Factor Model
      (FFM) and the Personality Psychopathology Five (PSY-5) using correlational and
      regression analyses. RESULTS: Sanislow's 3-factor model, containing affect
      dysregulation, behavioural dysregulation, and disturbed relations symptom
      dimensions, provided the best fit; the unidimensional model produced the worst.
      The symptom dimensions of the 3-factor model were differentiable from one another
      and had unique associations with the FFM and PSY-5 personality traits.
      CONCLUSION: BPD is a multidimensional construct.

PMID- 21959029
TI  - Prevalence of insomnia and its treatment in Canada.
AB  - OBJECTIVES: To estimate the prevalence of insomnia and examine its correlates
      (for example, demographics and physical and mental health) and treatments.
      METHODS: A sample of 2000 Canadians aged 18 years and older responded to a
      telephone survey about sleep, health, and the use of sleep-promoting products.
      Respondents with insomnia were identified using the Diagnostic and Statistical
      Manual of Mental Disorders, Fourth Edition, Text Revision, and the International
      Classification of Diseases, Tenth Edition, criteria. RESULTS: Among the sample,
      40.2% presented at least 1 symptom of insomnia (that is, trouble falling or
      staying asleep, or early morning awakening) for a minimum of 3 nights per week in
      the previous month, 19.8% were dissatisfied with their sleep, and 13.4% met all
      criteria for insomnia (that is, presence of 1 insomnia symptom 3 nights or more
      per week for at least 1 month, accompanied by distress or daytime impairment).
      Insomnia was associated with female sex, older age, and poorer self-rated
      physical and mental health. Thirteen per cent of respondents had consulted a
      health care provider for sleep difficulties once in their lifetime. Moreover, 10%
      had used prescribed medications for sleep in the previous year, 9.0% used natural
      products, 5.7% used over-the-counter products, and 4.6% used alcohol. There were
      differences between French- and English-speaking adults, with the former group
      presenting lower rates of insomnia (9.5%, compared with 14.3%) and consultation
      (8.7%, compared with 14.4%), but higher rates of prescribed medications (12.9%,
      compared with 9.3%) and the use of natural products (15.6%, compared with 7.4%).
      CONCLUSIONS: Insomnia is a prevalent condition, although few people seek
      professional consultation for this condition. Despite regional differences in the
      prevalence and treatments used to manage insomnia, prescribed medications remain
      the most widely used therapeutic option.

PMID- 21959030
TI  - Long-term impact of residual symptoms in treatment-resistant depression.
AB  - OBJECTIVE: Although commonly encountered, little work has defined the
      longitudinal course of treatment-resistant depression (TRD) and the influence of
      residual posttreatment symptoms on longer-term outcome. The aim of our study was
      to assess the impact of posttreatment clinical states on longer-term outcome.
      METHOD: Patients (n = 118) with TRD received specialist inpatient treatment and
      were followed-up for a median of 3 years. Longitudinal outcome dichotomized into
      good and poor outcome was used as the primary outcome and functional measures
      were used as secondary outcomes. RESULTS: Among 118 treated patients, 40 (34%)
      entered clinical remission, 36 (31%) entered partial remission, and 42 (37%)
      remained in episode at discharge. At follow-up, 35% had longitudinally defined
      poor outcome. Posttreatment clinical status was the main predictor of both poor
      and good outcome. Nearly 50% of patients achieved postdischarge recovery, and
      subsequently had longer-term outcome, comparable with patients discharged in
      remission. Patients who remained in episode posttreatment were more
      symptomatically and functionally impaired. CONCLUSION: Posttreatment clinical
      states are a useful guide to clinicians for projecting the longer-term outcome of
      patients with TRD. The persistence of residual or syndromal symptoms predicts a
      poorer longer-term outcome, whereas treatment to remission is associated with
      better outcomes.

PMID- 21959031
TI  - A meta-analysis of the efficacy of pregabalin in the treatment of generalized
      anxiety disorder.
AB  - OBJECTIVE: Generalized anxiety disorder (GAD) is a chronic anxiety disorder that
      leads to significant functional impairment and reduced quality of life.
      Pregabalin is a novel analogue of the inhibitory neurotransmitter gamma amino
      butyric acid, which has been proposed as a treatment for a range of conditions
      including GAD. This study examined the efficacy of pregabalin for GAD across
      published trials, using a meta-analytic method. METHOD: This study examined the 7
      published placebo-controlled trials of GAD using pregabalin, and, using meta
      analytic techniques, we calculated the effect size of treatment with pregabalin
      (compared with placebo) on a total of 1352 people. RESULTS: The overall effect
      size of pregabalin in the treatment of GAD was Hedges' g = 0.364, with an effect
      size of 0.349 on psychic anxiety symptoms and of 0.239 on somatic anxiety
      symptoms. CONCLUSION: Pregabalin is an efficacious therapy for GAD, although
      effect sizes are smaller than those from earlier studies. Limitations and future
      research directions are discussed.

PMID- 21959032
TI  - Prevalence of psychiatric disorder in lone fathers and mothers: examining the
      intersection of gender and family structure on mental health.
AB  - OBJECTIVE: While mothers head the majority of single-parent households, the
      percentage of father-headed, lone-parent households has increased in recent
      years. However, current mental health research on single parents focuses almost
      exclusively on single mothers. In this analysis, we disaggregate the unique and
      combined effects of gender and family structure on the mental health of fathers
      and mothers. METHODS: We used the Canadian Community Health Survey: Mental Health
      and Well-Being, a nationally representative population health survey. In this
      survey, 769 and 1964 lone fathers and mothers, respectively, and 5340 and 5505
      married or cohabitating fathers and mothers, respectively, with at least 1 child
      aged 25 years or younger living at home, were identified. We also used the World
      Mental Health Composite International Diagnostic Interview (WMH-CIDI) to provide
      diagnoses for various anxiety and mood disorders and a revised version of the WHM
      CIDI to identify substance use disorders (SUDs). RESULTS: Lone fathers and lone
      mothers have higher rates of mood disorders and SUDs than their married
      counterparts. Comparing lone parents, mothers had higher rates of anxiety
      disorders (10.7%, compared with 4.9%) and mood or anxiety disorders (19.9%,
      compared with 11.1%) than fathers but were not significantly different across
      total disorders when SUD was included. Social support significantly moderated
      effects for single-parent status and gender. Social support appears to be more of
      a protective factor for lone fathers than among lone mothers. CONCLUSIONS:
      Similar to lone mothers, lone fathers are at greater risk of psychiatric
      disorders than their married counterparts, indicating that this disadvantaged
      family structure has negative consequences for all parents.

PMID- 21959033
TI  - That pesky placebo and CYP 450.

PMID- 21959034
TI  - Increase in IL-21 producing T-cells in patients with systemic lupus
      erythematosus.
AB  - INTRODUCTION: Systemic lupus erythematosus (SLE) is an autoimmune disease
      accompanied by a disturbed T-cell balance skewed towards effector T-cells, in
      particular Th17-cells. The novel cytokine interleukin-21 (IL-21) is suggested to
      be crucial for triggering T-cell responses towards IL-17 producing cells. Thus,
      we aimed to investigate the ability of T-cells to produce IL-21 and IL-17 in SLE
      patients. METHODS: Peripheral blood of 34 SLE patients and 18 healthy controls
      (HC) was stimulated with phorbol myristate acetate (PMA) and calcium ionophore
      (Ca-Io). Percentages of IL-21- and IL-17A expressing T-cells were analysed by
      flow cytometry. The expression levels of the transcription factors B-cell
      lymphoma-6 (BCL-6) and factors retinoid-related orphan receptor (ROR-gammat) were
      assessed in T-cells by real-time RT-PCR and flow cytometry. Additionally, IL-21
      receptor (IL-21R) expression on B- and T-cells of patients and HC was analyzed.
      RESULTS: Significantly increased percentages of IL-21 expressing CD4+ T-cells and
      CD8+ T-cells were found in SLE patients as compared to HC. The percentages of IL
      21+ CD4+ T-cells and CD8+ T-cells correlated significantly with the percentages
      of IL-17A+ CD4+ T-cells and CD8+ T-cells, respectively. The relative expression
      of BCL-6 and ROR-gammat did not differ between SLE patients and HC. IL-21R
      expression occurred mainly on B-cells and was not different comparing SLE
      patients and HC. CONCLUSIONS: This study demonstrates an increased proportion of
      IL-21+ T-cells in SLE patients correlating with the proportion of IL-17+ T-cells.
      This suggests a pivotal role of IL-21 in the pathogenesis of SLE.

PMID- 21959035
TI  - Effects of intensive arm training with an electromechanical orthosis in chronic
      stroke patients: a preliminary study.
AB  - OBJECTIVES: To evaluate the use of an electromechanical device, comprising an
      exoskeleton, a static orthosis, and a glove, for functional rehabilitation of the
      elbow and hand in patients with hemiparesis, and to compare it with physical
      therapy rehabilitation. DESIGN: Pretest-posttest design. SETTING: Rehabilitation
      laboratory. PARTICIPANTS: Volunteer sample of persons (N=12) with persistent
      hemiparesis from a single, unilateral stroke within the past 3 to 36 months.
      INTERVENTIONS: The volunteers were randomly divided into 2 groups. One group was
      treated with a conventional program of physiotherapy, and another group
      participated in a training program in which an electromechanical orthosis was
      used. All volunteers received 24 sessions, held 3 times a week for 8 weeks. MAIN
      OUTCOME MEASURES: Modified Ashworth Scale (MAS), Fugl-Meyer Assessment (FMA), and
      electromyogram (EMG) amplitude. RESULTS: No statistical difference was found in
      the initial and final values of the MAS. Both groups showed a significant
      increase for the total scores of the FMA. However, only the group treated with
      the orthosis showed an increase in FMA scores related to the wrist and hand
      joint. The EMG analysis showed increased EMG amplitudes for all muscles in the
      group treated with the orthosis, whereas the group treated with physiotherapy
      showed gains in electromyographic activity only in the extensor digitorum
      communis. Intergroup comparison showed that the initial FMA scores of the
      wrist/hand were higher in the group treated with physiotherapy. However, after
      training, the scores in the group that used the orthosis were equivalent to those
      of the physiotherapy group. CONCLUSIONS: The results suggest that this device can
      be an auxiliary tool to help the conventional rehabilitation program of motor
      function of the affected upper extremity.

PMID- 21959036
TI  - Parasite infection and sand coarseness increase sand crab (Emerita analoga)
      burrowing time.
AB  - Parasites with indirect life cycles require trophic transmission from
      intermediate hosts to definitive (vertebrate) hosts. Transmission may be
      facilitated if parasite infection alters the behavior of intermediate hosts such
      that they are more vulnerable to predation. Vulnerability to predation may also
      be influenced by abiotic factors; however, rarely are the effects of parasites
      and abiotic factors examined simultaneously. The swash zone of sandy beaches is a
      particularly harsh environment. Sand crabs (Emerita analoga) burrow rapidly in
      the swash zone to avoid predators and dislodgment. We examined prevalence and
      abundance of the acanthocephalan parasite Profilicollis altmani in sand crabs,
      and investigated the synergistic effects of sand grain size (an important abiotic
      factor), parasite infection, body size and reproductive condition on burrowing
      speed in females, from three California sites. More heavily parasitized crabs
      burrowed more slowly, making them potentially more vulnerable to predation by
      marine bird definitive hosts. Ovigerous females harbored more parasites than non
      ovigerous females, but burrowed more quickly. All crabs burrowed slowest in the
      coarsest sand, and burrowing times increased with repeated testing, suggesting
      that it is energetically costly. Abiotic and biotic factors influence burrowing,
      and behavioral variation across sites may reflect the response to natural
      variation in these factors.

PMID- 21959037
TI  - The first BAFF gene cloned from the cartilaginous fish.
AB  - B-cell activating factor (BAFF), a member of the TNF family, is critical to the
      survival, proliferation, maturation, and differentiation of B-cells. In the
      present study, a CpBAFF was amplified from the white-spotted catshark
      (Chiloscyllium plagiosum) using RT-PCR and RACE (rapid amplification of cDNA end)
      techniques. To our knowledge, this is the first report of any BAFF gene being
      cloned from a cartilaginous fish. The open reading frame (ORF) of CpBAFF cDNA
      consists of 819 bases encoding a protein of 272 amino acids. This protein was
      found to contain a predicted transmembrane domain, a putative furin protease
      cleavage site, and a typical TNF homology domain corresponding to other
      identified BAFF homologues. Sequence alignment showed that CpBAFF shares 37-57%
      identity with BAFF amino acid sequences reported in other vertebrates. Three
      dimensional structure modeling analysis revealed a soluble mature portion of
      CpBAFF (CpsBAFF) with a long D-E loop specific to the BAFF gene, which has not
      been found in other reported TNF proteins. Phylogenetic reconstruction showed
      that CpBAFF is most closely related to other fish BAFFs and clusters with BAFF
      genes from higher vertebrates (reptiles, birds, and mammals). Real-time
      quantitative RT-PCR demonstrated that CpBAFF mRNA expression was high in the
      spleen but moderate in the kidney and branchia. Recombinant CpsBAFF fused to NusA
      His(6)-tag was efficiently expressed in Escherichia coli BL21 (DE3), and a
      molecular weight of approximately 83 kDa was determined using SDS-PAGE and
      Western blotting. In vitro MTT assay indicated that the purified pET43.1a (+)
      CpsBAFF protein can co-stimulate the proliferation of mammalian B-cells with anti
      IgM in a dose-dependent manner. The present findings not only present novel
      information that may be relevant to shark immunity but also provide some new
      insights into the origins and evolution of immunity in all vertebrates.

PMID- 21959038
TI  - Disturbance of the intestinal mucosal immune system of farmed Atlantic salmon
      (Salmo salar), in response to long-term hypoxic conditions.
AB  - The gastrointestinal (GI) tract has many important biological functions. One is
      to serve as a barrier between the fish and the external environment. A decreased
      physical barrier function of the intestine may lead to increased inflow of
      luminal content and subsequent activation of the intestinal mucosal immune
      system. This activation is governed by the ability of various compounds to induce
      cytokine release and immune cell activity, leading to an immune response. In
      mammals, the impact of stress on the intestinal barrier is well documented and
      results in increased intestinal permeability and thus increased stimulation of
      the mucosal immune system. Fish reared in sea cages may at times be exposed to
      unfavourable environmental conditions leading to chronic stress and disturbed
      intestinal integrity. This change in permeability may increase the exposure of
      the mucosal immune system to activating compounds. In the present study, the
      effect of a prolonged stress on the intestinal mucosal immune system of fish is
      therefore addressed. Atlantic salmon were exposed to low levels (50%) of
      dissolved oxygen (DO) for 6-7 weeks in consecutive experiments performed at 8 and
      16  degrees C. Immune parameters were assessed in terms of mRNA expression of the
      key cytokines, interleukin-1beta (IL-1beta), IL-8, IL-10, interferon-gamma
      (IFNgamma) and transforming growth factor-beta (TGFbeta) as well as the immune
      regulatory inhibitor of nuclear factor kappaB (IkappaB). In the experiment at 8 
      degrees C also mucosal neutrophil infiltration was monitored. Subjecting the fish
      to low DO levels at 8  degrees C resulted in an increased mucosal neutrophil
      infiltration together with a down-regulation of IkappaB. At the higher
      temperature, 16  degrees C, low DO levels created decreased expression of the pro
      inflammatory cytokine IL-1beta in both intestinal regions as well as an increased
      expression of IL-10 in the proximal intestine. These results suggest that
      husbandry conditions in sea cages with DO levels as low as 50% clearly affects
      the intestinal mucosal immune system and results in a chronic inflammation.
      Moreover, the effects of low DO levels on the immune factors examined were more
      pronounced in the 16  degrees C experiment suggesting additive effects of high
      temperatures.

PMID- 21959039
TI  - Molecular characterization of hepcidin gene from mud loach (Misgurnus mizolepis;
      Cypriniformes).
AB  - The gene encoding hepcidin, an antimicrobial peptide, was isolated and
      characterized in the mud loach Misgurnus mizolepis (Cypriniformes). Mud loach
      hepcidin shows a considerable degree of structural homology to other vertebrate
      hamp1 orthologues at both the gene and protein levels, particularly with respect
      to its tripartite genomic organization, typical transcription-factor-binding
      motifs in its promoter, and conserved cysteine residues in the mature cationic
      peptide. The mud loach possesses at least two allelic forms of hamp1, which are
      expected to be translated into the same hepcidin preproprotein. The two alleles
      are transmitted from parental fish to offspring with a Mendelian inheritance
      pattern, as demonstrated with polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP) genotyping. Southern blot hybridization analysis
      showed a high degree of polymorphisms in the restriction patterns of individuals.
      Mud loach hamp1 mRNA is predominantly expressed in the liver, although many other
      tissues showed detectable levels of hamp1 transcripts in RT-PCR assay.
      Lipopolysaccharide and bacterial challenges induced significant hamp1 expression,
      whereas hamp1 was not clearly stimulated by polyinosinic:polycytidylic acid
      [poly(I:C)] injection. Iron overload and Cu exposure also elevated hamp1
      transcripts in various tissues. The transcriptional activation of mud loach hamp1
      in response to these stimuli varied among tissue types, and the liver appears
      predominantly involved in hepcidin-mediated iron regulation. However, hepcidin
      expression in the kidney and spleen was preferentially modulated by inflammation
      mediated signals produced by immune challenges. Our results suggest that mud
      loach hepcidin has two basic functions, in iron regulation and antimicrobial
      activity, and that its transcription is also modulated by other environmental
      perturbations, including heavy metal exposure.

PMID- 21959040
TI  - Biochemical characterization of the very long-chain fatty acid elongase ELOVL7.
AB  - Very long-chain fatty acids (VLCFAs) have a variety of physiological functions
      and are related to numerous disorders. The key step of VLCFA elongation is
      catalyzed by members of the elongase family, ELOVLs. Mammals have seven ELOVLs
      (ELOVL1-7), yet none of them has been purified and analyzed. In the presented
      study we purified ELOVL7 and measured its activity by reconstituting it into
      proteoliposomes. Purified ELOVL7 exhibited high activity toward acyl-CoAs with
      C18 carbon chain length. The calculated K(m) values toward C18:3(n-3)-CoA and
      malonyl-CoA were both in the MUM range. We also found that progression of the
      VLCFA cycle enhances ELOVL7 activity.

PMID- 21959041
TI  - Anxiety and fear of childbirth as predictors of postnatal depression in
      nulliparous women.
AB  - BACKGROUND AND PURPOSE: Perinatal mental health problems have been studied in
      more than 90% of high income countries but this information is available only for
      10% of low and middle income countries. A study on the relationship between
      anxiety during pregnancy and postpartum depression has not been performed in
      Iran. This prospective study aimed to investigate whether anxiety and fear of
      childbirth during pregnancy is an independent predictor of postpartum depressive
      symptoms. METHODS: In this prospective longitudinal study participants were 160
      women with a gestational age of 28-30 weeks from 10 prenatal care clinics in Qom,
      Iran. Subjects were interviewed and the State-Trait Anxiety Inventory (STAI) and
      Childbirth Attitudes Questionnaire (CAQ) were completed at 28 and 38 weeks of
      gestation. They were followed up 45 days and 3 months after childbirth.
      Postpartum depression was defined as a score>=13 on the Edinburgh Postpartum
      Depression Scale (EPDS). RESULTS: Antenatal state anxiety (odds ratio [OR]=3.2;
      P=0.002 and OR=2.91; P=0.007 at 28 and 38 weeks of gestation, respectively) and
      trait anxiety (OR=3.33; P=0.001 and OR=3.30; P=0.003 at 28 and 38 weeks of
      gestation, respectively) increased the risk of postpartum depression 45 days
      after birth (P<0.05). Likewise, the presence of antenatal state and trait anxiety
      at 28 and 38 weeks of gestation significantly increased the risk of postpartum
      depression during the first three months after childbirth (P<0.05). On the
      contrary, prenatal fear of childbirth was not a significant predictor of
      postpartum depression symptoms (P>0.05). CONCLUSIONS: The findings from this
      study suggest that antenatal state and trait anxiety, assessed by interview, is
      an important predictor of postpartum depression. Therefore, it should be
      routinely screened in order to develop specific preventive interventions.

PMID- 21959042
TI  - Chemerin activates fibroblast-like synoviocytes in patients with rheumatoid
      arthritis.
AB  - INTRODUCTION: Chemerin is a chemotactic agonist identified as a ligand for
      ChemR23 that is expressed on macrophages and dendritic cells (DCs). In this
      study, we analyzed the expression of chemerin and ChemR23 in the synovium of
      rheumatoid arthritis (RA) patients and the stimulatory effects of chemerin on
      fibroblast-like synoviocytes (FLSs) from RA patients. METHODS: Chemerin and
      ChemR23 expression in the RA synovium was ascertained by immunohistochemistry and
      Western blot analysis. Chemerin expression on cultured FLSs was analyzed by
      ELISA. ChemR23 expression on FLSs was determined by immunocytochemistry and
      Western blot analysis. Cytokine production from FLSs was measured by ELISA. FLS
      cell motility was evaluated by utilizing a scrape motility assay. We also
      examined the stimulating effect of chemerin on the phosphorylation of mitogen
      activated protein kinase (MAPK), p44/42 mitogen-activated protein kinase
      (ERK1/2), p38MAPK, c-Jun N-terminal kinase (JNK)1/2 and Akt, as well as on the
      degradation of regulator of NF-kappaB (IkappaBalpha) in FLSs, by Western blot
      analysis. RESULTS: Chemerin was expressed on endothelial cells and synovial
      lining and sublining cells. ChemR23 was expressed on macrophages, immature DCs
      and FLSs and a few mature DCs in the RA synovium. Chemerin and ChemR23 were
      highly expressed in the RA synovium compared with osteoarthritis. Chemerin and
      ChemR23 were expressed on unstimulated FLSs. TNF-alpha and IFN-gamma upregulated
      chemerin production. Chemerin enhanced the production of IL-6, chemokine (C-C
      motif) ligand 2 and matrix metalloproteinase 3 by FLSs, as well as increasing FLS
      motility. The stimulatory effects of chemerin on FLSs were mediated by activation
      of ERK1/2, p38MAPK and Akt, but not by JNK1/2. Degradation of IkappaB in FLSs was
      not promoted by chemerin stimulation. Inhibition of the ERK1/2, p38MAPK and Akt
      signaling pathways significantly suppressed chemerin-induced IL-6 production.
      Moreover, blockade of the p38MAPK and Akt pathways, but not the ERK1/2 pathway,
      inhibited chemerin-enhanced cell motility. CONCLUSIONS: The interaction of
      chemerin and ChemR23 may play an important role in the pathogenesis of RA through
      the activation of FLSs.

PMID- 21959043
TI  - Modulating autophagy: a strategy for cancer therapy.
AB  - Autophagy is a process in which long-lived proteins, damaged cell organelles, and
      other cellular particles are sequestered and degraded. This process is important
      for maintaining the cellular microenvironment when the cell is under stress. Many
      studies have shown that autophagy plays a complex role in human diseases,
      especially in cancer, where it is known to have paradoxical effects. Namely,
      autophagy provides the energy for metabolism and tumor growth and leads to cell
      death that promotes tumor suppression. The link between autophagy and cancer is
      also evident in that some of the genes that regulate carcinogenesis, oncogenes
      and tumor suppressor genes, participate in or impact the autophagy process.
      Therefore, modulating autophagy will be a valuable topic for cancer therapy. Many
      studies have shown that autophagy can inhibit the tumor growth when autophagy
      modulators are combined with radiotherapy and/or chemotherapy. These findings
      suggest that autophagy may be a potent target for cancer therapy.

PMID- 21959045
TI  - Efficacy and safety of bevacizumab plus chemotherapy in Chinese patients with
      metastatic colorectal cancer: a randomized phase III ARTIST trial.
AB  - The efficacy and safety of bevacizumab with modified irinotecan, leucovorin
      bolus, and 5-fluorouracil intravenous infusion (mIFL) in the first-line treatment
      of metastatic colorectal cancer (mCRC) has not been well evaluated in randomized
      clinical trials in Chinese patients. We conducted a phrase III trial in which
      patients with previously untreated mCRC were randomized 2:1 to the mIFL
      [irinotecan (125 mg/m(2)), leucovorin (20 mg/m(2)) bolus, and 5-fluorouracil
      intravenous infusion (500 mg/m(2)) weekly for four weeks every six weeks] plus
      bevacizumab (5 mg/kg every two weeks) group and the mIFL group, respectively. Co
      primary objectives were progression-free survival (PFS) and 6-month PFS rate. In
      total, 214 patients were enrolled. Our results showed that addition of
      bevacizumab to mIFL significantly improved median PFS (4.2 months in the mIFL
      group vs. 8.3 months in the bevacizumab plus mIFL group, P < 0.001), 6-month PFS
      rate (25.0% vs. 62.6%, P < 0.001), median overall survival (13.4 months vs. 18.7
      months, P = 0.014), and response rate (17% vs. 35%, P = 0.013). Grades 3 and 4
      adverse events included diarrhea (21% in the mIFL group and 26% in the
      bevacizumab plus mIFL group) and neutropenia (19% in the mIFL group and 33% in
      the bevacizumab plus mIFL group). No wound-healing complications or congestive
      heart failure occurred. Our results suggested that bevacizumab plus mIFL is
      effective and well tolerated as first-line treatment for Chinese patients with
      mCRC. Clinical benefit and safety profiles were consistent with those observed in
      pivotal phase III trials with mainly Caucasian patients.

PMID- 21959044
TI  - Molecular genetics of ependymoma.
AB  - Brain tumors are the leading cause of cancer death in children, with ependymoma
      being the third most common and posing a significant clinical burden. Its
      mechanism of pathogenesis, reliable prognostic indicators, and effective
      treatments other than surgical resection have all remained elusive. Until
      recently, ependymoma research was hindered by the small number of tumors
      available for study, low resolution of cytogenetic techniques, and lack of cell
      lines and animal models. Ependymoma heterogeneity, which manifests as variations
      in tumor location, patient age, histological grade, and clinical behavior,
      together with the observation of a balanced genomic profile in up to 50% of
      cases, presents additional challenges in understanding the development and
      progression of this disease. Despite these difficulties, we have made significant
      headway in the past decade in identifying the genetic alterations and pathways
      involved in ependymoma tumorigenesis through collaborative efforts and the
      application of microarray-based genetic (copy number) and transcriptome profiling
      platforms. Genetic characterization of ependymoma unraveled distinct mRNA-defined
      subclasses and led to the identification of radial glial cells as its cell type
      of origin. This review summarizes our current knowledge in the molecular genetics
      of ependymoma and proposes future research directions necessary to further
      advance this field.

PMID- 21959046
TI  - Chloroquine enhances the cytotoxicity of topotecan by inhibiting autophagy in
      lung cancer cells.
AB  - Although the anti-malaria drug chloroquine (CQ) has been shown to enhance
      chemotherapy and radiation sensitivity in clinical trials, the potential
      mechanisms underlying this enhancement are still unclear. Here, we examined the
      relevant mechanisms by which the multipotent CQ enhanced the cytotoxicity of
      topotecan (TPT). The lung cancer cell line A549 was treated with TPT alone or TPT
      combined with CQ at non-cytotoxic concentrations. Cell viability was assessed
      using the MTT assay. The percentage of apoptotic cells and the presence of a side
      population of cells were both determined by flow cytometry. Autophagy and the
      expression of Bcl-2 family proteins were examined by Western blotting. The
      accumulation of YFP-LC3 dots and the formation of acidic vesicular organelles
      were examined by confocal microscopy. CQ sensitized A549 cells to TPT and
      enhanced TPT-induced apoptosis in a Bcl-2 family protein-independent fashion. CQ
      inhibited TPT-induced autophagy, which modified the cytotoxicity of TPT. However,
      CQ failed to modify the transfer of TPT across the cytoplasmic membrane and did
      not increase lysosomal permeability. This study showed that CQ at non-cytotoxic
      concentrations potentiated the cytotoxicity of TPT by interfering with autophagy,
      implying that CQ has significant potential as a chemotherapeutic enhancer.

PMID- 21959047
TI  - EGFR inhibitors sensitize non-small cell lung cancer cells to TRAIL-induced
      apoptosis.
AB  - Apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL) can be regulated by the epidermal growth factor (EGF) signaling pathway.
      In this study, recombinant adenoviral vectors that encode TRAIL gene from the
      hTERT/RGD promoter (AdTRAIL) was combined with drugs including gefitinib,
      elotinib, and cetuximab that inhibit EGFR and the EGF signaling pathway in non
      small cell lung cancer (NSCLC) cell lines to investigate their antitumor
      activity. In vitro, compared to single reagent, AdTRAIL combined with EGFR
      inhibitors reduced proliferation and enhanced apoptosis in H460, A549, and SW1573
      cell lines. Western blot results suggested that these effects were relative to up
      regulation of pro-apoptosis protein BAX and down-regulation of p-AKT. In vivo,
      AdTRAIL combined with cetuximab resulted in a significant growth reduction in
      H460 xenografts without damage to the main organs of nude mice. Histological
      examination and TUNEL analyses of xenografts showed that cetuximab enhanced cell
      apoptosis induced by AdTRAIL. These results indicate that EGFR inhibitors
      enhanced AdTRAIL anti-tumor activity in NSCLC cell lines and that inhibiting the
      AKT pathway played an important role in this enhancement.

PMID- 21959048
TI  - Rapamycin induces differentiation of glioma stem/progenitor cells by activating
      autophagy.
AB  - Glioma stem/progenitor cells (GSPCs) are considered to be responsible for the
      initiation, propagation, and recurrence of gliomas. The factors determining their
      differentiation remain poorly defined. Accumulating evidences indicate that
      alterations in autophagy may influence cell fate during mammalian development and
      differentiation. Here, we investigated the role of autophagy in GSPC
      differentiation. SU-2 cells were treated with rapamycin, 3-methyladenine (3-MA)
      plus rapamycin, E64d plus rapamycin, or untreated as control. SU-2 cell
      xenografts in nude mice were treated with rapamycin or 3-MA plus rapamycin, or
      untreated as control. Western blotting and immunocytochemistry showed up
      regulation of microtubule-associated protein light chain-3 (LC3)-II in rapamycin
      treated cells. The neurosphere formation rate and the number of cells in each
      neurosphere were significantly lower in the rapamycin treatment group than in
      other groups. Real-time PCR and immunocytochemistry showed down-regulation of
      stem/progenitor cell markers and up-regulation of differentiation markers in
      rapamycin-treated cells. Transmission electron microscopy revealed autophagy
      activation in rapamycin-treated tumor cells in mice. Immunohistochemistry
      revealed decreased Nestin-positive cells and increased GFAP-positive cells in
      rapamycin-treated tumor sections. These results indicate that rapamycin induces
      differentiation of GSPCs by activating autophagy.

PMID- 21959049
TI  - Association between single nucleotide polymorphisms on chromosome 17q and the
      risk of prostate cancer in a Chinese population.
AB  - In European populations, 7 single nucleotide polymorphisms (SNPs) on chromosome
      17q, 3 SNPs on 17q12, and 4 SNPs on 17q24.3 were recently identified to be
      closely related to the risk of prostate cancer by a genome-wide association
      study. In Japanese populations, the correlation between 2 SNPs on 17q and the
      risk of prostate cancer and tumor aggressiveness was also confirmed by a large
      scale experiment. However, whether 17q is associated with prostate cancer and its
      clinical manifestations in Chinese populations is still unknown. Therefore, we
      conducted a case-control study in a northern Chinese population and tested 2
      SNPs, rs4430796 and rs1859962, on 17q in 124 prostate cancer patients and 111
      controls using polymerase chain reaction-high resolution melting curve (PCR-HRM)
      combined with sequencing. We analyzed the association of the 2 SNPs with the risk
      of prostate cancer as well as patients' lifestyles, onset ages, Gleason scores,
      PSA levels, and pathologic stages. We found a significant difference in the G
      allele of SNP rs1859962 (P = 0.035, OR = 1.51, 95% CI = 1.03-2.21) but not in the
      rs4430796 genotype frequency or allele frequency distribution between prostate
      cancer patients and the controls (P > 0.05). Neither of the SNPs was
      significantly associated with the onset age, Gleason score, PSA level, pathologic
      stage, or other clinical indicators of patients with prostate cancer (P > 0.05).
      Our results show that polymorphism of the G allele of SNP rs1859962 is associated
      with the risk of prostate cancer in a Chinese population.

PMID- 21959050
TI  - Cyclosporine, prednisone, and high-dose immunoglobulin treatment of
      angioimmunoblastic T-cell lymphoma refractory to prior CHOP or CHOP-like regimen.
AB  - Angioimmunoblastic T-cell lymphoma (AITL) is a rare, distinct subtype of
      peripheral T-cell lymphoma, possessing an aggressive course and poor prognosis
      with no standard therapy. Twelve patients who have failed at least two initial
      CHOP or CHOP-like regimens were enrolled in this study and treated with
      individualized cyclosporine (CsA), prednisone (PDN), and monthly, high-dose
      intravenous immunoglobulin (HDIVIG). The dose of CsA was adjusted individually
      based on the blood trough concentration of CsA and renal function. All patients
      were examined for response, toxicity and survival. The most significant
      toxicities (>= grade 2) were infection (16.7%), renal insufficiency (8.3%),
      hypertension (8.3%), diabetes (8.3%) and insomnia (16.7%). Discontinuation of
      treatment occurred in one patient (8.3%) due to grade 3 renal toxicity and
      subsequent grade 4 pulmonary infection. Treatment-related death was not observed.
      The overall response rate was 75.0% (complete response, 33.3%; partial response,
      41.7%). With a median follow-up of 25.5 months, the median duration of response
      was 20 months (range, 12 to 49 months) and the median progression-free survival
      (PFS) was 25.5 months (range, 10 to 56 months). The 2-year PFS rate was 81.5%.
      Our findings indicate the combination of CsA, PDN and HDIVIG is an effective
      salvage regimen for refractory or relapsed AITL with predictable and manageable
      toxicity.

PMID- 21959051
TI  - In vitro evolution of an atrazine-degrading population under cyanuric acid
      selection pressure: evidence for the selective loss of a 47 kb region on the
      plasmid ADP1 containing the atzA, B and C genes.
AB  - The adaptation of microorganisms to pesticide biodegradation relies on the
      recruitment of catabolic genes by horizontal gene transfer and homologous
      recombination mediated by insertion sequences (IS). This environment-friendly
      function is maintained in the degrading population but it has a cost which could
      diminish its fitness. The loss of genes in the course of evolution being a major
      mechanism of ecological specialization, we mimicked evolution in vitro by sub
      culturing the atrazine-degrading Pseudomonas sp. ADP in a liquid medium
      containing cyanuric acid as the sole source of nitrogen. After 120 generations, a
      new population evolved, which replaced the original one. This new population grew
      faster on cyanuric acid but showed a similar cyanuric acid degrading ability.
      Plasmid profiles and Southern blot analyses revealed the deletion of a 47 kb
      region from pADP1 containing the atzABC genes coding for the enzymes that turn
      atrazine into cyanuric acid. Long PCR and sequencing analyses revealed that this
      deletion resulted from a homologous recombination between two direct repeats of a
      110-bp, identical to ISPps1 of Pseudomonas huttiensis, flanking the deleted 47 kb
      region. The loss of a region containing three functional genes constitutively
      expressed thereby constituting a genetic burden under cyanuric acid selection
      pressure was responsible for the gain in fitness of the new population. It
      highlights the IS-mediated plasticity of the pesticide-degrading potential and
      shows that IS not only favours the expansion of the degrading genetic potential
      thanks to dispersion and duplication events but also contribute to its reduction
      thanks to deletion events.

PMID- 21959052
TI  - Comparative effectiveness reviews need to pay as much attention to external
      validity as to internal validity risks of bias.

PMID- 21959053
TI  - The Agency for Healthcare Research and Quality (AHRQ) effective health care (EHC)
      program methods guide for comparative effectiveness reviews: keeping up-to-date
      in a rapidly evolving field.

PMID- 21959054
TI  - Anticipating the future: automatic prediction failures in schizophrenia.
AB  - People with schizophrenia often misperceive sensations and misinterpret
      experiences, perhaps contributing to psychotic symptoms. These misperceptions and
      misinterpretations might result from an inability to make valid predictions about
      expected sensations and experiences. Healthy normal people take advantage of
      neural mechanisms that allow them to make predictions unconsciously, facilitating
      processing of expected sensations and distinguishing the expected from the
      unexpected. In this paper, we focus on two types of automatic, unconscious
      mechanisms that allow us to predict our perceptions. The first involves
      predictions made via innate mechanisms basic to all species in the animal kingdom
      - the efference copy and corollary discharge mechanisms. They accompany our
      voluntary movements and allow us to suppress sensations resulting from our
      actions. We study this during talking, and show that auditory cortical response
      to the speech sounds during talking is reduced compared to when they are played
      back. This suppression is reduced in schizophrenia, suggesting a failure to
      predict the sensations resulting from talking. The second mechanism involves
      implicitly learning what to expect from the current context of events. We study
      this by observing the brain's response to an unexpected repetition of an event,
      when a change would have been predicted. That patients have a reduced response
      suggests they failed to predict that it was time for a change. Both types of
      predictions should happen automatically and effortlessly, allowing for economic
      processing of expected events and orientation to unexpected ones. These
      prediction failures characterize the diagnosis of schizophrenia rather than
      reflecting specific symptoms.

PMID- 21959055
TI  - Renal and glycemic effects of high-dose chromium picolinate in db/db mice:
      assessment of DNA damage.
AB  - This study examined renal and glycemic effects of chromium picolinate [Cr(pic)3]
      supplementation in the context of its purported potential for DNA damage. In
      preventional protocol, male obese diabetic db/db mice were fed diets either
      lacking or containing 5, 10 or 100 mg/kg chromium as Cr(pic)3 from 6 to 24 weeks
      of age; male lean nondiabetic db/m mice served as controls. Untreated db/db mice
      displayed increased plasma glucose and insulin, hemoglobin A1c, renal tissue
      advanced glycation end products, albuminuria, glomerular mesangial expansion,
      urinary 8-hydroxydeoxyguanosine (an index of oxidative DNA damage) and renal
      tissue immunostaining for gammaH2AX (a marker of double-strand DNA breaks)
      compared to db/m controls. Creatinine clearance was lower in untreated db/db mice
      than their db/m controls, while blood pressure was similar. High Cr(pic)3 intake
      (i.e., 100-mg/kg diet) mildly improved glycemic status and albuminuria without
      affecting blood pressure or creatinine clearance. Treatment with Cr(pic)3 did not
      increase DNA damage despite marked renal accumulation of chromium. In
      interventional protocol, effects of diets containing 0, 100 and 250 mg/kg
      supplemental chromium, from 12 to 24 weeks of age, were examined in db/db mice.
      The results generally revealed similar effects to those of the 100-mg/kg diet of
      the preventional protocol. In conclusion, the severely hyperglycemic db/db mouse
      displays renal structural and functional abnormalities in association with DNA
      damage. High-dose Cr(pic)3 treatment mildly improves glycemic control, and it
      causes moderate reduction in albuminuria, without affecting the histopathological
      appearance of the kidney and increasing the risk for DNA damage.

PMID- 21959056
TI  - Endoleaks with the AneuRx graft: a longer-term, single-center study.
AB  - PURPOSE: To report the frequency of endoleaks after endovascular aneurysm repair
      (EVAR) with the AneuRx graft. MATERIAL AND METHODS: The study group included 121
      consecutive patients treated with the first-generation AneuRx graft before
      December 2005, which ensured a potential minimum follow-up of 5 years. RESULTS:
      Thirty-seven patients (31%) had 45 different endoleaks at varying times in their
      follow-up. There were 18 type I endoleaks (15%), 56% of which developed more than
      5 years after EVAR. All 12 type Ia endoleaks were associated with dilation of the
      neck of the aneurysm by a mean of 8.5 mm at a median follow-up of 4 years. Ten of
      the 12 type Ia endoleaks were judged to have very favorable necks for EVAR. Five
      additional patients being followed had documented neck dilation and/or migration
      without evidence of endoleak or aneurysm enlargement. All type II endoleaks were
      noted in the first 2 years, and one persisted untreated for 9 years. CONCLUSIONS:
      Type I endoleaks continue to appear over time, and 56% occurred at 5 years or
      later after EVAR. All were associated with dilation at the attachment site, and
      all type Ia endoleaks had migration. As type Ia endoleaks may not always be
      amenable to endovascular repair, EVAR should be considered a less attractive
      option for some patients whose life expectancy is predicted to exceed 10 years.

PMID- 21959057
TI  - Development of an animal model for radiofrequency ablation of primary, virally
      induced hepatocellular carcinoma in the woodchuck.
AB  - PURPOSE: To develop a consistent and reproducible method in an animal model for
      studies of radiofrequency (RF) ablation of primary hepatocellular carcinoma
      (HCC). MATERIALS AND METHODS: Fifteen woodchucks were inoculated with woodchuck
      hepatitis virus (WHV) to establish chronic infections. When serum gamma-glutamyl
      transpeptidase levels became elevated, the animals were evaluated with
      ultrasound, and, in most cases, preoperative magnetic resonance (MR) imaging to
      confirm tumor development. Ultimately, RF ablation of tumors was performed by
      using a 1-cm probe with the animal submerged in a water bath for grounding.
      Ablation effectiveness was evaluated with contrast-enhanced MR imaging and gross
      and histopathologic analysis. RESULTS: RF ablation was performed in 15
      woodchucks. Modifications were made to the initial study design to adapt
      methodology for the woodchuck. The last 10 of these animals were treated with a
      standardized protocol using a 1-cm probe that produced a consistent area of tumor
      necrosis (mean size of ablation, 10.2 mm * 13.1 mm) and led to no complications.
      CONCLUSIONS: A safe, reliable and consistent method was developed to study RF
      ablation of spontaneous primary HCC using chronically WHV-infected woodchucks, an
      animal model of hepatitis B virus-induced HCC.

PMID- 21959059
TI  - First trimester diagnosis of forked cord in monoamniotic twin pregnancy.
AB  - A 29-year-old healthy woman at 10 weeks gestation was suspected for monoamniotic
      twin pregnancy, thus referred for evaluation and treatment. Ultrasound
      examination confirmed intrauterine monoamniotic twin gestation with central
      insertion of both umbilical cords by brief conjoined part (9 mm) - comprising a
      forked umbilical cord. Early diagnosis, planned prenatal care and close
      surveillance allowed preventing perinatal mortality.

PMID- 21959058
TI  - Hepatocellular necrosis, apoptosis, and proliferation after transcatheter
      arterial embolization or chemoembolization in a standardized rabbit model.
AB  - PURPOSE: To evaluate the effect of transcatheter arterial chemoembolization
      versus transcatheter arterial embolization on hepatocellular damage, apoptosis,
      proliferation, and proinflammatory response in a rabbit VX2 tumor model.
      MATERIALS AND METHODS: Rabbits implanted with VX2 tumors in left liver lobes were
      randomly divided into three groups: a control group (n = 9) that underwent
      infusion of distilled water into the left hepatic artery, an embolization group
      (n = 15) that underwent left hepatic artery embolization with polyvinyl alcohol
      (PVA) particles, and a chemoembolization group (n = 15) that underwent left
      hepatic artery infusion of a mixture of 10-hydroxycamptothecin and iodized oil
      followed by PVA embolization. Serum and liver samples were collected at 6 hours,
      3 days, and 7 days postoperatively. Liver damage was measured by liver function
      tests and histologic analysis. Ki-67 immunohistochemistry and terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling
      were performed to quantify proliferating and apoptotic cells. Serum tumor
      necrosis factor (TNF)-alpha levels were measured to assess proinflammatory
      response. RESULTS: Compared with embolization, chemoembolization caused liver
      injury with a greater increase in serum alanine aminotransferase and aspartate
      aminotransferase levels on days 3 and 7; histologic analysis showed increased
      hepatic necrosis in adjacent liver tissue beginning at day 3 and increased serum
      levels of TNF-alpha at 6 hours. By contrast, chemoembolization resulted in a
      slower increase in hepatocyte proliferation. Additionally, increased apoptotic
      hepatocytes were observed after embolization and chemoembolization. CONCLUSIONS:
      In contrast to embolization, nonsuperselective transcatheter arterial
      chemoembolization increased hepatocellular damage and stimulated systemic
      proinflammatory cytokine release, but inhibited hepatocyte proliferation.

PMID- 21959060
TI  - Seropositivity is associated with insulin resistance in patients with early
      inflammatory polyarthritis: results from the Norfolk Arthritis Register (NOAR):
      an observational study.
AB  - INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of death in
      patients with inflammatory polyarthritis (IP), especially in seropositive
      disease. In established rheumatoid arthritis (RA), insulin resistance (IR) is
      increased and associated with CVD. We investigated factors associated with IR in
      an inception cohort of patients with early IP. METHODS: Patients with early IP
      (two or more swollen joints for four or more weeks), aged 18 to 65 years, seen
      within 24 months of symptom onset were recruited from the Norfolk Arthritis
      Register (NOAR), a primary-care-based inception cohort. Assessment included joint
      examination, current and prior therapy and completion of the Health Assessment
      Questionnaire. Fasting blood was taken for measurement of CVD risk factors,
      rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), C-reactive
      protein (CRP), and insulin levels. IR was calculated using the homeostatic model
      assessment (HOMA-IR). We examined factors associated with IR using univariate and
      multivariable linear regression models. RESULTS: A total of 196 patients,
      including 59 (30%) males, were studied with a median (interquartile range, IQR)
      age and IP symptom duration of 49 (40 to 57) years and 6.7 (4.6 to 10.7) months,
      respectively. After age and gender adjustment, HOMA-IR was associated with
      obesity, (beta-Coefficient (95% CI); 1.60 (0.96, 2.24)), higher systolic and
      diastolic blood pressure (0.03 (0.01, 0.05) and 0.04 (0.01, 0.08) respectively),
      triglycerides (1.06 (0.54, 1.57)), and HDL (-1.38 (-2.17,-0.58)). HOMA-IR was
      associated with serological status and this association persisted after
      adjustment for classic CVD risk factors and other IP-related variables (RF beta
      Coefficient (95% CI); 0.87 (0.20, 1.53) and ACPA beta-Coefficient (95% CI); 1.42
      (0.70, 2.15)). CONCLUSIONS: Seropositivity for RF or ACPA was associated with IR
      in this early IP cohort. This association may, in part, explain why seropositive
      patients have excess CVD mortality.

PMID- 21959061
TI  - [Dietetic factors associated with prostate cancer: protective effects of
      Mediterranean diet].
AB  - OBJECTIVE: To review diet risk factors (RF) implied, more or less evidence-based,
      in the etiopathology of prostate carcinoma (PC), especially those that
      characterize the traditional Mediterranean diet (MD). MATERIAL AND METHODS:
      Literature review of PC related diet RF in MedLine, CancerLit, Science Citation
      Index y Embase. Search profiles were "Dietetic Factors/Nutritional
      Factors/Mediterranean Diet/Primary Prevention", and "Prostate Cancer". RESULTS:
      Diet RF are associated with 35% of cancer mortality and 10-12% of PC mortality.
      The main diet RF, implied in the development of PC but with a protective effect,
      which are considered characteristic of MD are: high daily ingestion of vegetarian
      products (cereals, legumes, dried and fresh fruits, tubers, vegetables..); olive
      oil as main lipid source; low intake of animal saturated fat, processed red meat,
      milk and dairy products; regular consumption of small fish; and low alcohol
      intake (wine with meals). The MD contains many phytoactive compounds (lycopene,
      lupeol, quercetin, genistein, carnosol, resveratrol, catechins, vitamins..) with
      PC protective effects. CONCLUSIONS: Diet RF have a role on prostatic
      carcinogenesis. Further epidemiologic studies with better designs are needed to
      clarify PC related diet RF. PC risk is reduced in persons on MD compared with
      those on Western diet. The preventive effect of MD is due to the great number and
      quality of phytochemicals with antioxidant and antinflammatory properties that
      contains.

PMID- 21959062
TI  - [Role of mitogen-activated protein kinase (MAPK) in the sporadic renal cell
      carcinoma].
AB  - CONTEXT: Only on the basis of the involvement of the vhl suppressor gene in the
      cases of renal cell carcinomas (RCC), the involvement of the signaling pathway
      between the pVHL and the Hypoxia inducible factor 1, alpha (HIF-1alpha) has been
      evaluated because of the need to find new diagnostic and prognostic and response
      to drugs markers. EVIDENCE SYNTHESIS: The overexpression of HIF-1alpha confers
      better prognosis in clear cell type RCC (ccRCC). Furthermore, HIF-1alpha
      regulates other genes, specifically that of the carbon anhydrase IX (CA-IX),
      whose overexpression is practically only of the ccRCC and its determination is
      useful for this subtype. However, the involvement of the CA-IX has not been
      demonstrated in the prognosis or in the response to immunomodulators or
      antiangiogenics. Therefore, it is necessary to make a global evaluation of all
      this pathway: pVHL -> HIF-1alpha -> CA-IX, and even the analysis of other
      proteins and signaling pathways that also control the HIF-1alpha activity. In the
      latter case, the MAPK are critical in the HIF-1alpha activation, there being
      evidence on the experimental level of the control on its activity. although its
      clinical role as a biomarkers has not been established. Although the role of the
      MAPK in the phenomena of resistance to conventional chemotherapy and radiotherapy
      has been demonstrated, it has not been demonstrated in response to sorafenib, an
      important piece of information if we consider that it is an inhibitor of several
      protein kinases. Recently, it has been observed that the MAPK may be involved in
      the responses to different therapies, included those based on tyrosine kinase
      inhibitors. CONCLUSIONS: The confirmation of these data would suppose an
      explanation of the variation observed between patients who, with the same
      functional alteration of the vhl gene, have a different biological, clinical
      behavior and better selection of non-surgical therapies.

PMID- 21959063
TI  - [The effect of diet induced obesity on testicular tissue and serum oxidative
      stress parameters].
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of diet induced
      obesity on semen parameters and serum antioxidant enzyme levels. MATERIAL AND
      METHODS: Six-week-old male rats were randomized into three groups are as follows:
      group 1 (n=10) received a control diet, group 2 (n=9) received a high-fat diet
      and group 3 (n=11) received high-fat diet plus anastrozole. At the completion of
      a 10-week period, testicular tissues were obtained and spermatogenesis was
      evaluated with Johnsen Score System. The normal Johnsen Score was accepted as
      >9.39. In addition, serum antioxidant enzyme levels, triglyceride, cholesterol,
      testosterone, luteinizing hormone (LH), follicle stimilating hormone (FSH) and
      estradiol levels were measured in serum. RESULTS: Body weight were significantly
      increased in mice fed with a high-fat diet compared to normal diet (P<.05). The
      mean triglyceride levels was 64.00+/-20.48 mg/dl, 98.89+/-27.80 mg/dl and 95.27+/
      15.02 mg/dl in group 1, group 2 and group 3, respectively (P<.05). Male rats fed
      with a high-fat diet had significantly lower levels of testosterone compared with
      the control diet male rats (P=.005). Testicular pathology revealed that Johnsen
      Score System were 9.60+/-0.15, 8.72+/-1.81 and 9.29 in group 1, group 2 and group
      3, respectively (P=.169). In addition serum nitric oxide (NO) levels were higher
      in group 2 and group 3 compared to group 1 (P<.05). CONCLUSION: As a result it
      may be concluded that obesity may induce oxidative stress and decrease
      testosterone levels. These changes may alter testicular functions and
      consequently it may be speculated that obesity can be important causative factor
      in the etiology of the male infertility.

PMID- 21959064
TI  - [Metabolic syndrome and hormone profile in patients with erectile dysfunction].
AB  - OBJECTIVES: To demonstrate the existence of relation between metabolic syndrome
      and erectile dysfunction and to analyze the hormone profile of these patients
      regarding a healthy population group. MATERIAL AND METHODS: A case-control study
      was designed with 65 men divided into 2 groups according to presence or non
      presence of erectile dysfunction. Group A was made up of 37 men with erectile
      dysfunction and group B by 28 healthy men without erectile dysfunction. Ages
      ranged from 40 to 65 years. The presence of metabolic syndrome according to the
      ATPIII definition, performance of physical exercise, smoking habit, body mass
      index and complete hormone profile including testosterone -total, free and
      bioavailability, were studied. RESULTS: Greater presence of metabolic syndrome
      was detected among men of Group A (72.9%) versus those of group B (17.8%)
      (p=0.0001). Among the parameters that make up the metabolic syndrome, there are
      differences between both groups in systolic and diastolic blood pressure, fast
      blood sugar and abdominal circumference, all these differences being significant.
      After performing multivariate analysis between the metabolic syndrome and
      erectile dysfunction adjusted for age, BMI, International Index for Erectile
      Function (IIEF), physical exercise and smoking habit, we have observed an
      independent significant relation between the metabolic syndrome and erectile
      dysfunction. We have not found differences between both groups in any hormone
      parameter. CONCLUSION: A relationship is found between metabolic syndrome and
      erectile dysfunction. Thus, it seems recommendable to perform the metabolic
      profile and cardiovascular risk study in these patients.

PMID- 21959065
TI  - [Clinical management of patient with benign prostatic hyperplasia in Spain].
AB  - OBJECTIVES: To identify clinical management of benign prostatic hyperplasia (BPH)
      in Spain and its associated health care resources. MATERIAL AND METHODS: A
      qualitative cross-sectional study was conducted through telephone interviews to
      general practitioners (GP) and urologists. Information about diagnosis,
      pharmacologic treatment and follow-up was collected. Results were clustered
      according to the key variables considered as drivers of clinical practice
      patterns: BPH diagnosis, severity classification, treatment initiation and follow
      up of patients. RESULTS: 153 GP and 154 urologists participated in the study. 7
      different clinical patterns were identified in primary care (PC). Resource use
      during diagnosis is relatively homogeneous, reporting a range of 2.0 to 2.6
      visits employed and being the most frequent test performed PSA and urine test.
      Follow-up is heterogeneous; frequency of follow-up visits oscillates from 3.2 to
      7.0 visits/patient/year and type of tests performed is different among patterns
      and within the same pattern. In Urology, 3 clinical patterns were identified.
      Resource use is homogeneous in the diagnosis and in the follow-up; urologists
      employed 2 visits in diagnosis and a range of 2.1 to 3.2 visits/patient/year in
      the follow-up. The most frequent tests both in diagnosis and follow-up are PSA
      and digital test. CONCLUSIONS: BPH management shows variability in PC,
      identifying 7 different clinical practice patterns with different resource use
      during the follow-up among patterns and within the same pattern. The
      implementation of clinical guidelines could be justified to reduce heterogeneity.

PMID- 21959066
TI  - [Effects of pelvic floor muscle training on quality of life of a group of women
      with urinary incontinence: randomized controlled trial].
AB  - OBJECTIVE: To evaluate the effects of Kinesiotherapy on function and level of
      pressure of pelvic floor muscle and quality of life (QOL) of a group of women
      with urinary incontinence (UI). MATERIALS AND METHODS: This is a randomized
      controlled pilot trial. Thirty women (age 60.87+/-9.05 years) were evaluated,
      before and after 12 weeks of treatment, for urinary loss, pelvic floor muscle
      function and pressure; and quality of life (QOL). Volunteers were randomly
      allocated into two groups: Kinesiotherapy Group and Control Group. The
      Kinesiotherapy Group protocol consisted of 12 1-hour sessions with exercises to
      strengthen pelvic floor muscle and information for UI. The Control Group did not
      receive any treatment during the corresponding time. The data were analyzed by
      non-parametric Wilcoxon and Mann-Whitney test. The significance level was 5%.
      RESULTS: The Kinesiotherapy Group presented a significant improvement in urinary
      loss (p=0.053), pelvic floor muscle function (p<0.006) and pressure (p=0.0014)
      and in some domains of Kings Health Questionnaire for QOL assessment:
      incontinence impact (p=0.034), limitations of daily activities (p=0.025), sleep
      and disposition (p=0.018) and also gravity domains (p=0.004). No differences were
      found in the control group for any variables. CONCLUSION: The protocol to
      strengthen the pelvic floor muscle used by the Kinesiotherapy Group was effective
      to improve the UI, QOL, function and pressure of pelvic floor muscle contraction.

PMID- 21959067
TI  - Factors involved in the persistence of stress urinary incontinence from pregnancy
      to 2 years post partum.
AB  - OBJECTIVE: To identify factors involved in the persistence of stress urinary
      incontinence (SUI) from pregnancy to 2 years post partum. METHOD: In a
      longitudinal study at Donostia Hospital, San Sebastian, Spain, 458 primigravid
      women were recruited from April to October 2007. SUI was diagnosed via the 2002
      International Continence Society definition. Severity was assessed via the
      Incontinence Severity Index, and impact on quality of life via the International
      Consultation on Incontinence Questionnaire. Means (Student t test and analysis of
      variance) and percentages (chi(2) and Fisher exact tests) were compared, and
      multiple logistic regression analysis was performed with variables that were
      significant or close to significant in a univariate analysis (P<0.2). RESULTS:
      Among 272 eligible women attending follow-up at 2 years post partum, 26 (9.5%)
      women reported persistent SUI since pregnancy. Incontinence severity was slight
      or moderate in most cases and the impact on quality of life was low. A higher
      body mass index (BMI) in pregnant women at term was the only factor found to be
      associated with persistent SUI (odds ratio 1.19; 95% confidence interval 1.08
      1.32). CONCLUSION: Higher BMI in pregnant women at term was an independent risk
      factor for the persistence of SUI from pregnancy to 2 years post partum.

PMID- 21959068
TI  - Effects of valerian on the severity and systemic manifestations of dysmenorrhea.
AB  - OBJECTIVE: To evaluate the impact of valerian-a herb with sedative effects and
      antispasmodic effects on smooth muscles-on the severity of dysmenorrhea. METHODS:
      In a double-blind, randomized, placebo-controlled trial, 100 students were
      randomly assigned to receive valerian (n=49) or placebo (n=51). Valerian (dose
      255 mg) was given 3 times daily for 3 days beginning at the onset of
      menstruation, for 2 consecutive menstrual cycles. At baseline and during the
      intervention cycles, the pain severity was evaluated with a visual analog scale
      and the systemic manifestations were assessed using a multidimensional verbal
      scale. RESULTS: The pain severity at baseline did not differ significantly
      between the groups. After the intervention, the pain severity was significantly
      reduced in both groups (P<0.001), but the extent of the reduction was larger in
      the valerian group, with the difference between the 2 groups being statistically
      significant (P<0.05). The total scores of the systemic manifestations associated
      with dysmenorrhea decreased after the intervention, but there was no significant
      difference between the groups, with the exception for syncope (P<0.05).
      CONCLUSION: Valerian seems to be an effective treatment for dysmenorrhea,
      probably because of its antispasmodic effects.

PMID- 21959069
TI  - First-trimester maternal serum 25-hydroxyvitamin D3 status and pregnancy outcome.
AB  - OBJECTIVE: To determine the pregnancy outcome as a function of the first
      trimester serum 25-hydroxyvitamin D(3) [25(OH)D] status and to compare the
      25(OH)D levels in the first and third trimesters. METHODS: Pregnant women (n=466)
      tested for serum 25(OH)D levels during the first trimester were followed up until
      the end of pregnancy, and the obstetric and neonatal outcomes were compared in
      reference to the baseline 25(OH)D status. The third-trimester 25(OH)D levels were
      additionally measured in a subset of women (n=148). RESULTS: The obstetric and
      neonatal outcomes did not vary as a function of the first-trimester 25(OH)D
      status. Neither did the 25(OH)D levels vary as a function of pregnancy outcomes.
      Overall, the 25(OH)D levels significantly decreased from the first to the third
      trimester. The first- and third-trimester 25(OH)D levels of samples initially
      taken during autumn/winter were significantly lower than those that were
      initially taken during spring/summer. Interestingly, the decrease in 25(OH)D
      levels during the third trimester was independent of the season of sampling.
      CONCLUSION: The pregnancy outcome was independent of the first-trimester 25(OH)D
      status. Overall, the 25(OH)D levels significantly decreased in the third
      trimester. More research in this area is warranted.

PMID- 21959070
TI  - Efficacy of the levonorgestrel-releasing intrauterine system in uterine
      leiomyoma.
AB  - OBJECTIVE: To evaluate the efficacy of the levonorgestrel-releasing intrauterine
      system (LNG-IUS) in reducing menstrual blood loss (MBL) in myoma-related
      menorrhagia and to assess the effect of the LNG-IUS on uterine and leiomyoma
      volume. METHODS: A prospective comparative study investigated the effect of LNG
      IUS use in women with myoma-related menorrhagia (n=54) and women with idiopathic
      menorrhagia (n=50). The outcome was assessed in terms of reductions in MBL and in
      myoma and uterine volume. RESULTS: Within 1 month of LNG-IUS insertion, the
      Pictorial Blood Loss Assessment Chart score in the myoma group fell by 86.8%
      (P<0.0001). At 3, 12, 24, 36, and 48 months, the MBL was reduced by 92.1%, 97.4%,
      97.4%, 99.5%, and 99.5%, respectively, similar to the effect seen in the
      idiopathic menorrhagia group. The mean uterine volume was significantly reduced
      in both groups, but the reduction was greater in the group with leiomyomas
      (idiopathic menorrhagia, P=0.038; myoma-related menorrhagia, P=0.012). There was
      no statistically significant reduction in the myoma volume (P=0.409). CONCLUSION:
      Use of the LNG-IUS appears to lead to a significant reduction in the uterine
      volume of women with menorrhagia, as well as reducing the MBL in women with
      uterine leiomyomas.

PMID- 21959071
TI  - Comparison of the efficacy and safety of titrated oral misoprostol and a
      conventional oral regimen for cervical ripening and labor induction.
AB  - OBJECTIVE: To compare the efficacy and safety of titrated oral misoprostol and a
      conventional oral regimen for cervical ripening and labor induction. METHODS: A
      randomized double-blind trial of women with term singleton pregnancies with
      indications for labor induction. Participants were allocated to receive 20 mL of
      misoprostol solution (1 MUg/mL) orally every 1 hour for 4 doses then titrated to
      40 MUg every 1 hour (titrated group) or 50 MUg of misoprostol orally every 4
      hours up to 12 hours (conventional group). Primary outcomes were success rate of
      cervical ripening within 12 hours, interval from first dose until more favorable
      cervix or active labor occurred, and total dose of misoprostol. RESULTS: Sixty
      four participants were included. Mean total dose of misoprostol and incidence of
      tachysystole were significantly higher in the titrated compared with the
      conventional group (236.2+/-110.1 MUg vs 103.1 +/- 35.7 MUg; P=0.001 and 25.0% vs
      6.3%; P=0.03), whereas success rate, interval from drug administration to more
      favorable cervix and delivery, proportion of patients delivered vaginally within
      12 hours and 24 hours, need for oxytocin augmentation, cesarean delivery rate,
      maternal adverse effects and complications, and neonatal outcome were not
      significantly different (P>0.05). CONCLUSION: Conventional oral misoprostol is as
      effective as titrated misoprostol for cervical ripening and labor induction, but
      has a lower incidence of tachysystole and a lower total dose of misoprostol is
      required. ClinicalTrial.gov: NCT00886860.

PMID- 21959072
TI  - Possible role of serotonin transporter in irritable bowel syndrome: evidence from
      platelet investigation.

PMID- 21959073
TI  - Another earth: innate lymphoid cells and intestinal inflammation.

PMID- 21959074
TI  - Polyp in the gallbladder.

PMID- 21959075
TI  - An unusual case with upper gastrointestinal bleeding.

PMID- 21959076
TI  - Analgesics block more than pain.

PMID- 21959077
TI  - An unusual case of multiple small ulcerations throughout the GI tract.

PMID- 21959079
TI  - Blueberry muffin rash and thrombocytopenia in a newborn with mucolipidosis type
      II (I-cell disease) masquerading as congenital infections.

PMID- 21959078
TI  - Source cancellation profiles of electroencephalography and
      magnetoencephalography.
AB  - Recorded electric potentials and magnetic fields due to cortical electrical
      activity have spatial spread even if their underlying brain sources are focal.
      Consequently, as a result of source cancellation, loss in signal amplitude and
      reduction in the effective signal-to-noise ratio can be expected when distributed
      sources are active simultaneously. Here we investigate the cancellation effects
      of EEG and MEG through the use of an anatomically correct forward model based on
      structural MRI acquired from 7 healthy adults. A boundary element model (BEM)
      with four compartments (brain, cerebrospinal fluid, skull and scalp) and highly
      accurate cortical meshes (~300,000 vertices) were generated. Distributed source
      activations were simulated using contiguous patches of active dipoles. To
      investigate cancellation effects in both EEG and MEG, quantitative indices were
      defined (source enhancement, cortical orientation disparity) and computed for
      varying values of the patch radius as well as for automatically parcellated gyri
      and sulci. Results were calculated for each cortical location, averaged over all
      subjects using a probabilistic atlas, and quantitatively compared between MEG and
      EEG. As expected, MEG sensors were found to be maximally sensitive to signals due
      to sources tangential to the scalp, and minimally sensitive to radial sources.
      Compared to EEG, however, MEG was found to be much more sensitive to signals
      generated antero-medially, notably in the anterior cingulate gyrus. Given that
      sources of activation cancel each other according to the orientation disparity of
      the cortex, this study provides useful methods and results for quantifying the
      effect of source orientation disparity upon source cancellation.

PMID- 21959080
TI  - Promoter mutation is a common variant in GJC2-associated Pelizaeus-Merzbacher
      like disease.
AB  - Pelizaeus-Merzbacher-like disease (PMLD) is a clinically and genetically
      heterogeneous neurological disorder of cerebral hypomyelination. It is clinically
      characterised by early onset (usually infantile) nystagmus, impaired motor
      development, ataxia, choreoathetoid movements, dysarthria and progressive limb
      spasticity. We undertook autozygosity mapping studies in a large consanguineous
      family of Pakistani origin in which affected children had progressive lower limb
      spasticity and features of cerebral hypomyelination on MR brain imaging. SNP
      microarray and microsatellite marker analysis demonstrated linkage to chromosome
      1q42.13-1q42.2. Direct sequencing of the gap junction protein gamma-2 gene, GJC2,
      identified a promoter region mutation (c.-167A>G) in the non-coding exon 1. The
      c.-167A>G promoter mutation was identified in a further 4 individuals from two
      families (who were also of Pakistani origin) with clinical and radiological
      features of PMLD in whom previous routine diagnostic screening of GJC2 had been
      reported as negative. A common haplotype was identified at the GJC2 locus in the
      three mutation-positive families, consistent with a common origin for the
      mutation and likely founder effect. This promoter mutation has only recently been
      reported in GJC2-PMLD but it has been postulated to affect the binding of the
      transcription factor SOX10 and appears to be a prevalent mutation, accounting for
      ~29% of reported patients with GJC2-PMLD. We propose that diagnostic screening of
      GJC2 should include sequence analysis of the non-coding exon 1, as well as the
      coding regions to avoid misdiagnosis or diagnostic delay in suspected PMLD.

PMID- 21959081
TI  - Minimally invasive presacral approach for revision of an Axial Lumbar Interbody
      Fusion rod due to fall-related lumbosacral instability: a case report.
AB  - INTRODUCTION: The purpose of this study was to describe procedural details of a
      minimally invasive presacral approach for revision of an L5-S1 Axial Lumbar
      Interbody Fusion rod. CASE PRESENTATION: A 70-year-old Caucasian man presented to
      our facility with marked thoracolumbar scoliosis, osteoarthritic changes
      characterized by high-grade osteophytes, and significant intervertebral disc
      collapse and calcification. Our patient required crutches during ambulation and
      reported intractable axial and radicular pain. Multi-level reconstruction of L1-4
      was accomplished with extreme lateral interbody fusion, although focal
      lumbosacral symptoms persisted due to disc space collapse at L5-S1.Lumbosacral
      interbody distraction and stabilization was achieved four weeks later with the
      Axial Lumbar Interbody Fusion System (TranS1 Inc., Wilmington, NC, USA) and rod
      implantation via an axial presacral approach.Despite symptom resolution following
      this procedure, our patient suffered a fall six weeks postoperatively with direct
      sacral impaction resulting in symptom recurrence and loss of L5-S1 distraction.
      Following seven months of unsuccessful conservative care, a revision of the Axial
      Lumbar Interbody Fusion rod was performed that utilized the same presacral
      approach and used a larger diameter implant. Minimal adhesions were encountered
      upon presacral re-entry. A precise operative trajectory to the base of the
      previously implanted rod was achieved using fluoroscopic guidance. Surgical
      removal of the implant was successful with minimal bone resection required. A
      larger diameter Axial Lumbar Interbody Fusion rod was then implanted and joint
      distraction was re-established. The radicular symptoms resolved following
      revision surgery and our patient was ambulating without assistance on post
      operative day one. No adverse events were reported. CONCLUSIONS: The Axial Lumbar
      Interbody Fusion distraction rod may be revised and replaced with a larger
      diameter rod using the same presacral approach.

PMID- 21959082
TI  - Design and pharmacological activity of glycinamide and N-methoxy amide
      derivatives of analogs and constitutional isomers of valproic acid.
AB  - A series of glycinamide conjugates and N-methoxy amide derivatives of valproic
      acid (VPA) analogs and constitutional isomers were synthesized and evaluated for
      anticonvulsant activity. Of all compounds synthesized and tested, only N-methoxy
      valnoctamide (N-methoxy-VCD) possessed better activity than VPA in the following
      anticonvulsant tests: maximal electroshock, subcutaneous metrazol, and 6-Hz (32
      mA) seizure tests. In mice, the ED(50) values of N-methoxy-VCD were 142 mg/kg
      (maximal electroshock test), 70 mg/kg (subcutaneous metrazol test), and 35 mg/kg
      (6-Hz test), and its neurotoxicity TD(50) was 118 mg/kg. In rats, the ED(50) of N
      methoxy-VCD in the subcutaneous metrazol test was 36 mg/kg and its protective
      index (PI=TD(50)/ED(50)) was >5.5. In the rat pilocarpine-induced status
      epilepticus model, N-methoxy-VCD demonstrated full protection at 200mg/kg,
      without any neurotoxicity. N-Methoxy-VCD was tested for its ability to induce
      teratogenicity in a mouse strain susceptible to VPA-induced teratogenicity and
      was found to be nonteratogenic, although it caused some resorptions.
      Nevertheless, a safety margin was still maintained between the ED(50) values of N
      methoxy-VCD in the mouse subcutaneous metrazol test and the doses that caused the
      resorptions. On the basis of these results, N-methoxy-VCD is a good candidate for
      further evaluation as a new anticonvulsant and central nervous system drug.

PMID- 21959083
TI  - Acute and long-term safety of external trigeminal nerve stimulation for drug
      resistant epilepsy.
AB  - Trigeminal nerve stimulation (TNS) is a novel therapy for drug-resistant
      epilepsy. We report in detail the safety of external TNS (eTNS), focusing on
      acute and long-term heart rate and systolic and diastolic blood pressure in
      response to TNS from the pilot feasibility study. The data indicate that eTNS of
      the infraorbital and supraorbital branches of the trigeminal nerve is safe and
      well tolerated.

PMID- 21959084
TI  - Stent implantation in aorto-ostial lesions: long-term follow-up and predictors of
      outcome.
AB  - AIMS: To compare the outcomes of drug-eluting (DES) vs. bare-metal (BMS) stents
      for stenting of native aorto-ostial lesions (AOL) and to identify predictors of
      major adverse cardio and cerebrovascular events (MACCE). METHODS AND RESULTS: A
      total of 181 patients (182 AOL) who underwent stenting of AOL were
      retrospectively identified: right-coronary artery in 130 (71.4%), left main in 52
      (28.6%). In-hospital event rate was 1.1% (two non-Q-wave myocardial infarctions).
      Follow-up was possible in 98.3%, median time=23.9 months (IQR 12.1-37.7). Event
      rates and survival MACCE-free were not significantly different between DES and
      BMS. After multivariate analysis, only the logistic EuroSCORE >10% predicted
      MACCE (HR=4.66, 95% CI: 2.38-9.12, p<0.001), whereas the predictors for TLR were
      age (HR=0.96, 95% CI: 0.92-1.00, p=0.039) and the stented artery (RCA vs. LM,
      HR=10.2, 95% CI: 1.37-75.45, p=0.024). CONCLUSIONS: AOL stenting can be performed
      with high success and low complication rates. At follow-up, no significant
      differences in event rates were found between DES and BMS; EuroSCORE>10% was the
      only predictor of MACCE.

PMID- 21959085
TI  - Comparing the toxic mechanism of synthesized zinc oxide nanomaterials by
      physicochemical characterization and reactive oxygen species properties.
AB  - We studied the toxicity of ZnO nanomaterials in terms of physicochemical
      characteristics and reactive oxygen species (ROS) properties. ZnO nanorods
      [synthesized at room temperature (ZnO-RT, length; 18.0+/-4.2 nm) and at 60 
      degrees C (ZnO-60, length; 80.5+/-6.8 nm)] were used to evaluate the potential
      toxicity upon growth velocity-related particle size. The cytotoxicity of ZnO-60
      was higher than that of ZnO-RT. We observed that the toxicity of ZnO-RT and ZnO
      60 was related with ROS formation by using antioxidant N-acetylcysteine and
      electron spin resonance. Also, we found that the source of toxicity was not
      related to Zn(2+) ions released from ZnO in 24h treatment. Our results indicate
      that toxicity of ZnO nanorods is caused by the amounts of ROS. Our study strongly
      suggests that size of nanomaterial is not the sole factor to be considered, thus,
      the development of appropriate criteria based on morphological/physicochemical
      characteristics as well as synthesis procedures is needed to evaluate the precise
      toxicity.

PMID- 21959086
TI  - The prognostic value of B-type natriuretic peptide after cardiac surgery: a
      comparative study between coronary artery bypass graft surgery and aortic valve
      replacement.
AB  - OBJECTIVES: The influence of the cardiac surgical procedure on B-type natriuretic
      peptide (BNP) for the identification of high-risk patients has not been
      evaluated. This study aimed to compare the prognostic utility of pre- and
      postoperative BNP in predicting adverse long-term outcome after coronary artery
      bypass graft (CABG) surgery and aortic valve replacement (AVR). DESIGN: A
      retrospective study. SETTING: A university teaching hospital. PARTICIPANTS: One
      hundred eighty-nine patients. MEASUREMENTS AND MAIN RESULTS: Preoperative, early
      postoperative (24 hours), and late postoperative (day 5) BNP levels were
      measured. Major adverse cardiac events (MACEs) within 12 months after surgery
      were chosen as study endpoints. The predictive abilities of BNP measurements were
      compared using receiver operating characteristic (ROC) curves. Patients were
      stratified by CABG surgery (n = 100) and AVR (n = 89). Thirty-four (18%) patients
      experienced 44 MACEs over the study period. Preoperative BNP values were
      significantly different between groups. Postoperative BNP gradually increased by
      431% on day 5 after CABG surgery and by 100% after AVR (both p < 0.001 v
      preoperative values). Pre- and early postoperative BNP values were accurate in
      predicting MACEs after AVR (areas under the ROC curves: 0.78 [95% confidence
      interval, 0.66-0.90] and 0.76 [95% confidence interval, 0.62-0.89], respectively)
      and inaccurate after CABG surgery (0.54 [95% confidence interval, 0.38-0.70] and
      0.54 [95% confidence interval, 0.36-0.73], respectively). The late postoperative
      BNP value was of limited value. CONCLUSIONS: BNP measurements should take into
      account the type of cardiac surgery. Whatever the time of measurement, BNP
      accurately predicts long-term adverse outcome in valve surgery patients. A late
      postoperative BNP measurement is useless after cardiac surgery.

PMID- 21959087
TI  - Concurrent infections are important for expression of porcine circovirus
      associated disease.
AB  - Porcine circovirus type 2 (PCV2) is the essential component of porcine circovirus
      disease (PCVD) as the disease syndrome is referred to in Europe and porcine
      circovirus associated disease (PCVAD) as it is referred to in North America.
      Singular PCV2 infection rarely results in clinical disease; however, PCVAD is
      often accelerated in onset, enhanced in severity and prolonged in duration by
      concurrent viral or bacterial infections. Due to its effect on the immune system,
      PCV2 has also been shown to enhance protozoal, metazoal, and fungal infections.
      Several retrospective or cross-sectional studies have investigated the presence
      and prevalence of various infectious agents associated with PCVAD under field
      conditions. Experimental models confirm that PCV2 replication and associated
      lesions can be enhanced by concurrent infection with other viruses or bacteria.
      The exact mechanisms by which concurrent pathogens upregulate PCV2 are unknown.
      Co-infections may promote PCV2 infection by increasing immune host cell
      replication and accumulation in tissues thereby enhancing targets for PCV2
      replication. It has also been proposed that co-infections interfere with PCV2
      clearance by alteration of cytokine production and profiles. The outcome of
      differences in timing of co-infections in PCV2-infected pigs is also likely very
      important and is an area where more research is needed. Given the current
      knowledge base, it is important that veterinarians do a thorough diagnostic
      investigation on herds where PCVAD is a recurrent problem in order to implement
      the most appropriate and cost effective intervention strategies.

PMID- 21959088
TI  - Maintaining class, producing gender: enhancement discourses about amphetamine in
      entertainment media.
AB  - BACKGROUND: Since the 1930s, amphetamine has been used for a variety of socially
      and medically condoned purposes including personal and performance enhancement.
      In the contemporary U.S., although amphetamine and its derivatives share a
      history, similar chemical composition, and physiological and psychiatric effects,
      they are typically treated and researched as two distinct groups: illegally
      produced methamphetamine and prescription amphetamine. This study is an
      examination of the social meanings of these categories and their users as
      represented in popular media. METHODS: To complement existing research on drug
      discourses in popular news media, this study analysed entertainment media: ten
      novels, three seasons of Breaking Bad, six television episodes, and eight movies.
      Media were coded inductively and deductively using tenets of critical discourse
      analysis and rhetorical criticism. The author identified discourses about user
      subject positions and ideologies pertaining to enhancement-related motivations
      for use. RESULTS: Two important themes emerged from this analysis that construct
      amphetamine use and users in ways that reflect, legitimize and reproduce class
      and gender ideologies. First, discourses illustrate that distinct meanings of
      methamphetamine versus prescription amphetamine are linked to expectations about
      the respective socioeconomic class and social status of their users. Second, the
      discourses reflect gendered values and ideals about productivity and sexuality.
      CONCLUSION: In reality, American cultural and political-economic contexts may
      encourage the use of amphetamine to meet a variety of social expectations and
      economic needs. However, many policy and prevention efforts surrounding
      amphetamine use disproportionately target methamphetamine users and women.
      Because policy and prevention efforts can be influenced as much by social values
      as by data, it is important to examine the many arenas in which social values are
      produced and disseminated.

PMID- 21959089
TI  - Calcium entry via TRPC6 mediates albumin overload-induced endoplasmic reticulum
      stress and apoptosis in podocytes.
AB  - Albumin, which is the most abundant component of urine proteins, exerts injurious
      effects on renal cells in chronic kidney diseases. However, the toxicity of
      albumin to podocytes is not well elucidated. Here, we show that a high
      concentration of albumin triggers intracellular calcium ([Ca(2+)](i)) increase
      through mechanisms involving the intracellular calcium store release and
      extracellular calcium influx in conditionally immortalized podocytes. The
      canonical transient receptor potential-6 (TRPC6) channel, which is associated
      with a subset of familial forms of focal segmental glomerulosclerosis (FSGS) and
      several acquired proteinuric kidney diseases, was shown to be one of the
      important Ca(2+) permeable ion channels in podocytes. Therefore we explored the
      role of TRPC6 on albumin-induced functional and structural changes in podocytes.
      It was found that albumin-induced increase in [Ca(2+)](i) was blocked by TRPC6
      siRNA or SKF-96365, a blocker of TRP cation channels. Long-term albumin exposure
      caused an up-regulation of TRPC6 expression in podocytes, which was inhibited by
      TRPC6 siRNA. Additionally, the inhibition of TRPC6 prevented the F-actin
      cytoskeleton disruption that is induced by albumin overload. Moreover, albumin
      overload induced expression of the endoplasmic reticulum (ER) stress protein
      GRP78, led to caspase-12 activation and ultimately podocyte apoptosis, all of
      which were abolished by the knockdown of TRPC6 using TRPC6 siRNA. These results
      support the view that albumin overload may induce ER stress and the subsequent
      apoptosis in podocytes via TRPC6-mediated Ca(2+) entry.

PMID- 21959090
TI  - Water reuse: >90% water yield in MBR/RO through concentrate recycling and CO2
      addition as scaling control.
AB  - Over 1.5 years continuous piloting of a municipal wastewater plant upgraded with
      a double membrane system (ca. 0.6 m(3) d(-1) of product water produced) have
      demonstrated the feasibility of achieving high water quality with a water yield
      of 90% by combining a membrane bioreactor (MBR) with a submerged ultrafiltration
      membrane followed by a reverse osmosis membrane (RO). The novelty of the proposed
      treatment scheme consists of the appropriate conditioning of MBR effluent prior
      to the RO and in recycling the RO concentrates back to the biological unit. All
      the 15 pharmaceuticals measured in the influent municipal sewage were retained
      below 100 ng L(-1), a proposed quality parameter, and mostly below detection
      limits of 10 ng L(-1). The mass balance of the micropollutants shows that these
      are either degraded or discharged with the excess concentrate, while only minor
      quantities were found in the excess sludge. The micropollutant load in the
      concentrate can be significantly reduced by ozonation. A low treated water
      salinity (<10 mM inorganic salts; 280 +/- 70 MUS cm(-1)) also confirms that the
      resulting product has a high water quality. Solids precipitation and inorganic
      scaling are effectively mitigated by lowering the pH in the RO feed water with
      CO(2) conditioning, while the concentrate from the RO is recycled to the
      biological unit where CO(2) is stripped by aeration. This causes precipitation to
      occur in the bioreactor bulk, where it is much less of a process issue. SiO(2) is
      the sole exception. Equilibrium modeling of precipitation reactions confirms the
      effectiveness of this scaling-mitigation approach for CaCO(3) precipitation,
      calcium phosphate and sulfate minerals.

PMID- 21959091
TI  - Fast and precise method for HPLC-size exclusion chromatography with UV and TOC
      (NDIR) detection: importance of multiple detectors to evaluate the
      characteristics of dissolved organic matter.
AB  - A new type of high-performance liquid chromatography (HPLC)-size exclusion
      chromatography (SEC) system with ultraviolet (UV) absorbance detection and non
      dispersive infrared (NDIR) detection of total organic carbon is described. The
      introduction of an online degassing tube and a low-volume HPLC column helped to
      reduce the analytical time and increase the sensitivity of the SEC system. This
      study is the first in which linear calibration curves (R(2)>0.99) were obtained
      for both UV absorbance and NDIR data for polystyrene sulfonate standards, which
      are the most suitable standards for molecular size analysis of aquatic humic
      substances as well as dissolved organic matter (DOM). Using the calibration
      curves, the molecular size distribution of DOM in water collected from Lake
      Kasumigaura and in pore water from lake sediments was estimated. Most of the DOM
      had a molecular weight less than 4000 Daltons (Da), and the amount of low
      molecular-weight DOM (~ 2000 Da) with low UV absorbance increased with depth in
      the sediment pore water. This result shows the importance of combining
      quantitative analysis by NDIR detection with qualitative analysis by UV detection
      to determine the chemical and physical properties of DOM. The possible sources
      and reactivity of DOM in Lake Kasumigaura and its sediment pore water are also
      discussed.

PMID- 21959092
TI  - The impact of pH on floc structure characteristic of polyferric chloride in a low
      DOC and high alkalinity surface water treatment.
AB  - The adjustment of pH is an important way to enhance removal efficiency in
      coagulation units, and in this process, the floc size, strength and structure can
      be changed, influencing the subsequent solid/liquid separation effect. In this
      study, an inorganic polymer coagulant, polyferric chloride (PFC) was used in a
      low dissolved organic carbon (DOC) and high alkalinity surface water treatment.
      The influence of coagulation pH on removal efficiency, floc growth, strength, re
      growth capability and fractal dimension was examined. The optimum dosage was
      predetermined as 0.150 mmol/L, and excellent particle and organic matter removal
      appeared in the pH range of 5.50-5.75. The structure characteristics of flocs
      formed under four pH conditions were investigated through the analysis of floc
      size, effect of shear and particle scattering properties by a laser scattering
      instrument. The results indicated that flocs formed at neutral pH condition gave
      the largest floc size and the highest growth rate. During the coagulation period,
      the fractal dimension of floc aggregates increased in the first minutes and then
      decreased and larger flocs generally had smaller fractal dimensions. The floc
      strength, which was assessed by the relationship of floc diameter and velocity
      gradient, decreased with the increase of coagulation pH. Flocs formed at pH 4.00
      had better recovery capability when exposed to lower shear forces, while flocs
      formed at neutral and alkaline conditions had better performance under higher
      shear forces.

PMID- 21959093
TI  - Sulfate radical-advanced oxidation process (SR-AOP) for simultaneous removal of
      refractory organic contaminants and ammonia in landfill leachate.
AB  - Typically, a mature landfill leachate contains high levels of non-biodegradable
      organics and ammonia nitrogen. Simultaneous removal of the both persistent
      leachate pollutants is a significant challenge. This paper reports the first
      scientific study to apply a sulfate radical (SO(4)(.-)) - based advanced
      oxidation process (SR-AOP) to treat a mature leachate, with an emphasis of
      concurrent removal of refractory organics and ammonia. In this study, all the
      experiments were run in a batch reactor with temperature control. In the thermal
      persulfate oxidation (TPO) process, persulfate (S(2)O(8)(2-)) was activated by
      heat to produce powerful oxidants, SO(4)(.-) (E(o) = 2.6 V). Three factors
      affecting the removal efficiencies of chemical oxygen demand (COD) and ammonia
      nitrogen were investigated, including initial solution pH (3-8.3), temperature
      (27-50  degrees C), and chemical dose (S(2)O(8)(2-):12COD(0) = 0.25-2.0).
      Typically, acidic pH (3-4), higher temperature, and higher dose favored the
      removal of COD and ammonia. At S(2)O(8)(2-):12COD(0) = 2 and 50  degrees C, the
      COD removal rates were 79% and 91% at pH 8.3 (no pH adjustment) and 4,
      respectively; and the ammonia nitrogen removal reached 100% at pH 8.3 or 4. SR
      AOP appears to be more advantageous over hydroxyl radical (OH?)-based advanced
      oxidation processes (HR-AOPs) because OH? almost does not oxidize ammonia.
      Furthermore, compared with Fenton treatment of the same batch leachate sample,
      the TPO could achieve a higher COD removal at an identical chemical dose. For
      example, COD removal was 40% at H(2)O(2):2.125COD(0) = 2 during Fenton treatment
      (pH 3), but 91% at S(2)O(8)(2-):12COD(0) = 2 during TPO (pH 4). These findings
      demonstrate that SR-AOP is a promising landfill leachate treatment method.

PMID- 21959094
TI  - [Ebrictus study. Functional results, survival, and potential years of life lost
      after the first stroke].
AB  - AIM: To determine the mortality, degree of dependence, survival, and years of
      life lost (YLL) after first episode of stroke. DESIGN: Cohort study. LOCATION:
      Community based register. PARTICIPANTS: A total of 553 subjects between 15-90
      years with a first episode of definitive or transitory stroke were recruited
      between 01/04/2006 and 31/03/2008. MEASUREMENTS: The analyses were performed with
      the use of time-to-event methods, according to the intention-to-treat principle.
      The level of dependency was assessed according to the Barthel Scale one year
      after stroke; YLL (1-70 years) from the mean life expectancies at birth; survival
      analysis by Kaplan-Meier's curves, bivariate analysis comparing the variables
      between patients who had survived and those who died, and Cox's multivariate.
      RESULTS: The mean age was 73.3 (+/-11.6 years. The mean time of follow-up was
      29.7 +/- 13,4 months, during which 26.6% of the patients died. The mean Barthel
      score fell by >20%, particularly among women. There was moderate or greater
      dependence in 41.5% (95%CI 30.6-52.8%) of the subjects. The overall accumulative
      probability of survival was 0.96 (95% CI 0.94-0.97) in the first month and 0.69
      (95% CI 0.65-0.72) in the fourth year. The thrombolytic treatment showed a
      protective effect on mortality, particularly among the women. The main predictive
      variables were, history of recurrent cardiovascular event (RR 6.7, 95% CI 2.2
      21.7) and aging (RR 1.08, 95% CI 1.01-1.2). The average YLL was 11.5/10000/year
      SD7.2, and higher among men. CONCLUSION: There are differences in functional
      outcome, mortality, and potential years of life lost by gender. A new
      cardiovascular event is an independent prognostic factor of survival.

PMID- 21959095
TI  - Training pediatric residents in a primary care clinic to help address
      psychosocial problems and prevent child maltreatment.
AB  - OBJECTIVE: The objectives of this study were to determine whether 1) residents
      trained in the SEEK (A Safe Environment for Every Kid) model would report
      improved attitudes, knowledge, comfort, competence, and practice regarding
      screening for psychosocial risk factors (parental depression, parental substance
      abuse, intimate partner violence, stress, corporal punishment, and food
      insecurity); 2) intervention residents would be more likely to screen for and
      assess those risk factors; and 3) families seen by intervention residents would
      report improved satisfaction with their child's doctor compared to families
      receiving standard care from control residents. METHODS: Pediatric residents in a
      university-based pediatrics continuity clinic were enrolled onto a randomized
      controlled trial of the SEEK model. The model included resident training about
      psychosocial risk factors, a Parent Screening Questionnaire, and a study social
      worker. Outcome measures included: 1) residents' baseline, 6-month, and 18-month
      posttraining surveys, 2) medical record review, and 3) parents' satisfaction
      regarding doctor-parent interaction. RESULTS: Ninety-five residents participated.
      In 4 of 6 risk areas, intervention residents scored higher on the self-assessment
      compared to control subjects, with sustained improvement at 18 months.
      Intervention residents were more likely than control subjects to screen and
      assess parents for targeted risk factors. Parents seen by intervention residents
      responded favorably regarding interactions with their doctor. CONCLUSIONS: The
      SEEK model helped residents become more comfortable and competent in screening
      for and addressing psychosocial risk factors. The benefits were sustained.
      Parents viewed the intervention doctors favorably. The model shows promise as a
      way of helping address major psychosocial problems in pediatric primary care.

PMID- 21959097
TI  - Pre-operative interventions (non-surgical and non-pharmacological) for patients
      with hip or knee osteoarthritis awaiting joint replacement surgery--a systematic
      review and meta-analysis.
AB  - OBJECTIVE: To determine if pre-operative interventions for hip and knee
      osteoarthritis provide benefit before and after joint replacement. METHOD:
      Systematic review with meta-analysis of randomised controlled trials (RCTs) of
      pre-operative interventions for people with hip or knee osteoarthritis awaiting
      joint replacement surgery. Standardised mean differences (SMD) were calculated
      for pain, musculoskeletal impairment, activity limitation, quality of life, and
      health service utilisation (length of stay and discharge destination). The GRADE
      approach was used to determine the quality of the evidence. RESULTS: Twenty-three
      RCTs involving 1461 participants awaiting hip or knee replacement surgery were
      identified. Meta-analysis provided moderate quality evidence that pre-operative
      exercise interventions for knee osteoarthritis reduced pain prior to knee
      replacement surgery (SMD (95% CI)=0.43 [0.13, 0.73]). None of the other meta
      analyses investigating pre-operative interventions for knee osteoarthritis
      demonstrated any effect. Meta-analyses provided low to moderate quality evidence
      that exercise interventions for hip osteoarthritis reduced pain (SMD (95%
      CI)=0.52 [0.04, 1.01]) and improved activity (SMD (95% CI)=0.47 [0.11, 0.83])
      prior to hip replacement surgery. Meta-analyses provided low quality evidence
      that exercise with education programs improved activity after hip replacement
      with reduced time to reach functional milestones during hospital stay (e.g., SMD
      (95% CI)=0.50 [0.10, 0.90] for first day walking). CONCLUSION: Low to moderate
      evidence from mostly small RCTs demonstrated that pre-operative interventions,
      particularly exercise, reduce pain for patients with hip and knee osteoarthritis
      prior to joint replacement, and exercise with education programs may improve
      activity after hip replacement.

PMID- 21959096
TI  - A novel self-evaluation tool to assess the team function of a child protection
      team.
AB  - OBJECTIVE: The aim of this study was to develop a reliable and valid self
      evaluation tool for use by child protection team (CPT) members. METHODS: An
      online survey was administered to members of 10 CPTs. The survey included the
      following 3 sections: 1) initial conditions (eg, team composition, resources), 2)
      enabling conditions (eg, team effort, strategy), and 3) team effectiveness (eg,
      team cohesion, meeting performance standards). Each section contained multiple
      subscales. Internal consistency was calculated using Cronbach alpha. To evaluate
      construct validity, the subscale scores of the most advanced teams who qualified
      as centers of excellence (n = 3) were compared with the subscale scores of the
      other teams (n = 7) to determine whether the tool could distinguish between the
      two. RESULTS: Of 116 team members, 83 (72%) completed the survey. The subscales
      exhibited good internal consistency (alpha = .71-.97). The 3 centers of
      excellence had significantly higher mean scores than the other 7 CPTs on the
      following subscales: incentives (in the initial conditions section, 61.46 vs
      38.89; P = .003), effort (in the enabling conditions section, 79.31 vs 67.70; P =
      .003), and professional growth (in the team effectiveness section, 83.89 vs
      80.40; P = .004). CONCLUSIONS: This novel survey demonstrates satisfactory test
      characteristics and can be used to assess CPT performance and identify areas for
      improvement.

PMID- 21959098
TI  - The association between meniscal and cruciate ligament damage and knee pain in
      community residents.
AB  - OBJECTIVE: To describe the frequency of meniscal and cruciate ligament damage by
      magnetic resonance imaging (MRI) and to examine its association with knee pain in
      community residents in Korea. METHODS: Participants were randomly chosen
      regardless of knee osteoarthritis (OA) or pain from the population-based Hallym
      Aging Study. Demographic and knee pain data were obtained by questionnaire.
      Radiographic evaluations consisted of weight-bearing knee A-P radiographs and 1.5
      T MRI scans. We assessed the integrities of the menisci and cruciate ligaments in
      the dominant knee of subjects without knee pain or in the more symptomatic knee
      among subjects with knee pain, and examined their association with knee pain
      using a logistic regression model. RESULTS: The mean age of the 358 study
      subjects was 71.8 years, and 51.4% were women. Meniscal and cruciate ligament
      damage were present in 49.7% and 8.0% of men and in 71.2% and 26.9% of women,
      respectively. The presence of meniscal damage was significantly associated with
      the presence of knee pain among subjects without radiographic knee OA (ROA), but
      not among subjects with ROA. The presence of cruciate ligament tear was
      associated with knee pain in subjects with or without ROA. The severity of knee
      pain was significantly correlated with medial meniscal damage grade but not with
      cruciate ligament tear. CONCLUSION: Incidental meniscal or cruciate findings on
      MRI were common in this elderly population. Among subjects without ROA, the
      presence of meniscal or cruciate damage was significantly associated with knee
      pain. The medial meniscal grade was significantly correlated with knee pain
      severity.

PMID- 21959099
TI  - WITHDRAWN: Implementation Science for nursing: Evidence needed! Call for papers
      for a Special Issue.
AB  - The Publisher regrets that this article is an accidental duplication of an
      article that has already been published, doi:<10.1016/j.ijnurstu.2011.09.001>.
      The duplicate article has therefore been withdrawn.

PMID- 21959100
TI  - The Lively Legs self-management programme increased physical activity and reduced
      wound days in leg ulcer patients: Results from a randomized controlled trial.
AB  - OBJECTIVE: Investigating the effectiveness of the Lively Legs program for
      promoting adherence with ambulant compression therapy and physical exercise as
      well as effects on leg ulcer recurrence. DESIGN: A randomized controlled trial.
      SETTING: Eleven outpatient clinics for dermatology in the Netherlands
      participated in the study. PATIENTS: 184 patients attending the outpatient clinic
      with leg ulcers based dominantly on a venous aetiology. Randomization was
      stratified by centre, age, sex and aetiology (purely venous or mixed).
      INTERVENTION: The intervention group received additionally to usual care,
      lifestyle counselling according to the Lively Legs program, the control group
      received care as usual. Patient behaviour on physical activity (IPAQ), adherence
      to compression therapy and wound status were assessed every 6 months during a
      follow-up period of 18 months. Data analysis was based on the intention to treat
      principle, using a generalized linear model with additive link function and
      Bernouilli distributions. Effects on recurrence were analyzed after the first
      ulcer had healed using proportional hazard regression. RESULTS: The results
      showed an increase in adherence with compression therapy in both groups, with no
      significant difference between the groups. The intervention group performed
      significantly better on conducting leg exercises (p<0.01) and 10 min walks at
      five days a week (p<0.01). There was no difference on reaching 30 min of walking
      on 5 days a week. The intervention group had less wound days (p<0.01), time till
      recurrence did not differ significantly (p=0.07). CONCLUSION: The Lively Legs
      program effectively increased the use of leg exercises and walking behaviour, and
      decreased wound time, however it did not significantly enhance use of compression
      stockings. Non significant effects regarding secondary outcomes may relate to the
      frailty of the sample.

PMID- 21959101
TI  - In vivo visualisation by three-dimensional optical coherence tomography of stress
      crazing of a bioresorbable vascular scaffold implanted for treatment of human
      coronary stenosis.

PMID- 21959102
TI  - Stockout risk analysis and minimization applied to hospital pharmacy management.
AB  - OBJECTIVE: To determine how many dispensary drugs should be in the safety stock
      in a tertiary hospital in accordance with the risk level and the number of days
      that the hospital is able to withstand a stockout. METHODS: We statistically
      analysed the infliximab order recorded over a period of 120 days. This drug is
      relevant for this study as it is costly and is immediately supplied to the
      clinic. Using the data records for purchasing and dispensing in our department,
      we created a table to compare the level of risk assumed with the number of units
      in stock and the number of days that the safety stock should last. In addition,
      we calculated how much stock there should be in accordance with different
      heuristic rules used by pharmacy departments. RESULTS: In the period being
      studied, the daily order was 11.4+/-14.8 units of infliximab. Using the
      methodology proposed, we discovered that there should be 79 units in the safety
      stock. Other hospital rules determine values of 47 and 119 units. CONCLUSIONS:
      The method proposed allows us to discover the risk level that is assumed when
      selecting the safety stock. Therefore, we are able to design a safety stock
      policy consistent with the risk level adopted. Under certain assumptions the
      safety stock quota provided by this method could be reduced. Lastly, there is a
      notable difference between the safety stock values suggested by different rules,
      as it has been shown in this article.

PMID- 21959104
TI  - Investigation of microemulsion microstructures and their relationship to
      transdermal permeation of model drugs: ketoprofen, lidocaine, and caffeine.
AB  - In this study, microemulsion microstructures, key formulation variables, and
      their relationship to drug transdermal permeation enhancement were investigated.
      A microemulsion system with high water soluble capacity was developed, using
      isopropyl myristate, Labrasol, and Cremophor EL as oil, surfactant, and co
      surfactant, respectively. The microstructures of the microemulsions were
      characterized by a combination of techniques including electrical conductivity
      measurement (EC), differential scanning calorimetry (DSC), electro-analytical
      cyclic voltammetry (CV), dynamic light scattering (DLS). Three microemulsion
      formulations with the model drugs at water contents of 20%, 40%, and 70%
      representing the microstructures of W/O, Bi-continuous, and O/W were prepared
      along the water dilution line of oil to surfactant ratio of 1/9. Skin permeation
      of hydrophobic and hydrophilic model drugs, ketoprofen, lidocaine, and caffeine
      in the microemulsion formulations was studied using Franz-cells and dermatomed
      porcine skin. Permeation of all drugs from microemulsions was enhanced
      significantly compared with the control propylene glycol formulation. The drug
      permeation flux and the cumulative permeation amount after 24h increased with
      water content in the microemulsions, thus correlated to the formulation
      microstructures of W/O, Bi-continuous, and O/W. The permeation of lipophilic
      drugs ketoprofen and lidocaine increased with water content in a more pronounced
      manner, which seemed to follow an exponential growth trend, while the permeation
      of hydrophilic drug caffeine appeared to increase linearly. Additionally, at the
      same water content, increasing oil content led to higher ketoprofen permeation.

PMID- 21959105
TI  - Raman spectroscopy of racemic ibuprofen: evidence of molecular disorder in phase
      II.
AB  - Low- and high-frequency Raman experiments in the 5-200 cm(-1) and 600-1800 cm(-1)
      ranges were carried out in the crystalline and amorphous states of ibuprofen. Low
      frequency investigations indubitably reveal the existence of a molecular disorder
      in the metastable phase (phase II), through the observation of quasielastic
      contribution below 30 cm(-1), and the absence of phonon peaks in the Raman
      susceptibility which mimics the density of vibrational states of an amorphous
      state. High-frequency Raman spectra indicate a local order in phase II similar to
      that in the glassy state. Both dynamic and static molecular disorder could
      contribute to the Raman signatures of the disorder in crystalline phase II. Raman
      investigations suggest that phase II can be considered as a transient metastable
      state in the devitrification process of ibuprofen upon heating from a far from
      equilibrium state toward the stable phase I.

PMID- 21959103
TI  - Postnatal serotonin type 2 receptor blockade prevents the emergence of anxiety
      behavior, dysregulated stress-induced immediate early gene responses, and
      specific transcriptional changes that arise following early life stress.
AB  - BACKGROUND: Early life adverse experience contributes to an enhanced
      vulnerability for adult psychopathology. Recent evidence indicates that serotonin
      type 2 (5-HT(2)) receptor function, implicated in the pathophysiology of mood and
      anxiety disorders, is significantly enhanced in the maternal separation model of
      early life stress. We examined whether postnatal 5-HT(2) receptor blockade would
      prevent the consequences of maternal separation on anxiety behavior and
      dysregulated gene expression. METHODS: Control and maternally separated litters
      received treatment with the 5-HT(2) receptor antagonist, ketanserin, or vehicle
      during postnatal life and were examined for effects on adult anxiety behavior,
      adult stress-induced immediate early gene expression responses, and
      transcriptional changes within the prefrontal cortex during postnatal life and in
      adulthood. RESULTS: Treatment with ketanserin during postnatal life blocked the
      long-lasting effects of maternal separation on anxiety behavior in the open field
      test and the elevated plus maze. Further, the dysregulated adult stress-induced
      expression pattern of the immediate early gene, Arc, observed in maternally
      separated animals was also prevented by postnatal ketanserin treatment.
      Ketanserin treatment normalized the alterations in the expression of specific
      genes in the prefrontal cortex of maternally separated animals, including changes
      in serotonin type 2A receptor messenger RNA expression during postnatal life and
      in genes associated with G-protein signaling in adulthood. CONCLUSIONS: Postnatal
      treatment with the 5-HT(2) receptor antagonist, ketanserin, blocked specific
      consequences of maternal separation, including anxiety behavior and dysregulated
      gene expression in the prefrontal cortex. Our results suggest that enhanced 5
      HT(2) receptor function may contribute to the emergence of anxiety behavior and
      perturbed stress responses following early life stress.

PMID- 21959106
TI  - Supported bilayer on a nanopatterned membrane as model PAMPA membranes.
AB  - Parallel-artificial membrane permeation assay (PAMPA) is widely used to rapidly
      measure drug permeability across a biological membrane. We have prepared model
      PAMPAs by supporting a lipid bilayer on a hydrated polymeric cushion adsorbed at
      the surface of a nanoporous alumina filter. In contrast to conventional PAMPAs,
      the natural fluidity of the bilayer is expected to be conserved in these model
      PAMPAs. The assembly was characterized by contact angle measurement and atomic
      force microscopy (AFM) and the supported membranes were mounted in a Franz cell
      setup to assess the permeability of acetaminophen and famotidine. The
      permeability profiles for the model PAMPA were compared to those of conventional
      PAMPA.

PMID- 21959107
TI  - Impact of short range hydrophobic interactions and long range electrostatic
      forces on the aggregation kinetics of a monoclonal antibody and a dual-variable
      domain immunoglobulin at low and high concentrations.
AB  - The purpose of this work was to determine the nature of long and short-range
      forces governing protein aggregation kinetics at low and high concentrations for
      a monoclonal antibody (IgG1) and a dual-variable-domain immunoglobulin (DVD-Ig).
      Protein-protein interactions (PPI) were studied under dilute conditions by
      utilizing the methods of static (B(22)) and dynamic light scattering (k(D)). PPI
      in solutions containing minimal ionic strengths were characterized to get
      detailed insights into the impact of ionic strength on aggregation.
      Microcalorimetry and susceptibility to denature at air-liquid interface were used
      to assess the tertiary structure and quiescent stability studies were conducted
      to study aggregation characteristics. Results for IgG1 showed that electrostatic
      interactions governed protein aggregation kinetics both under dilute and
      concentrated conditions (i.e., 5 mg/mL and 150 mg/mL). For DVD-Ig molecules, on
      the other hand, although electrostatic interactions governed protein aggregation
      under dilute conditions, hydrophobic forces clearly determined the kinetics at
      high concentrations. This manuscript shows for the first time that short-range
      hydrophobic interactions can outweigh electrostatic forces and play an important
      role in determining protein aggregation at high concentrations. Additionally,
      results show that although higher-order virial coefficients become significant
      under low ionic strength conditions, removal of added charges may be used to
      enhance the aggregation stability of dilute protein formulations.

PMID- 21959108
TI  - The CPP Tat enhances eGFP cell internalization and transepithelial transport by
      the larval midgut of Bombyx mori (Lepidoptera, Bombycidae).
AB  - Cell-Penetrating Peptides (CPPs) are short peptides that are able to translocate
      across the cell membrane a wide range of cargoes. In the past decade, different
      mammalian cell lines have been used to clarify the mechanism of CPPs penetration
      and to characterize the internalization process, which has been described either
      as an energy-independent direct penetration through the plasma membrane, or as
      endocytic uptake. Whatever the mechanism involved, the cell penetration
      properties of these peptides make their use very attractive as vector for
      promoting the cellular uptake of coupled bioactive macromolecules, such as
      peptides, proteins and oligonucleotides. Here we demonstrate, for the first time
      in insect, that cultured columnar cells from the larval midgut of Bombyx mori
      more readily internalize eGFP (enhanced Green Fluorescent Protein) when fused to
      CPP Tat. Tat-eGFP translocates across the plasma membrane of absorptive cells in
      an energy-independent and non-endocytic manner, since no inhibition of the fusion
      protein uptake is exerted by metabolic inhibitors and by drugs that interfere
      with the endocytic uptake. Moreover, the CPP Tat enhances the internalization of
      eGFP in the columnar cells of intact midgut tissue, mounted in a suitable
      perfusion apparatus, and the transepithelial flux of the protein. These results
      open new perspectives for effective delivery of insecticidal macromolecules
      targeting receptors located both within the insect gut epithelium and behind the
      gut barrier, in the hemocoel compartment.

PMID- 21959109
TI  - Fibroblast growth factor signaling in non-small-cell lung cancer.
AB  - Despite recent progress in the treatment on non-small cell lung cancer (NSCLC),
      outcomes remain suboptimal. Treatment advances that target the epidermal growth
      factor receptor (EGFR) and vascular endothelial growth factor (VEGF) signaling
      pathways highlight the need to understand the multiple convergent growth factor
      signaling pathways involved in the pathogenesis of NSCLC. Signaling through
      fibroblast growth factors (FGF), long recognized for its pro-angiogenic activity,
      has recently emerged as a contributing factor in the pathogenesis and progression
      of NSCLC through an autocrine signaling loop. In addition, this pathway may
      function as a mechanism of resistance to anti-EGFR and anti-VEGF treatment.
      Clinical experience with FGF receptor (FGFR) inhibitors is mounting, and more
      specific inhibitors of this signaling pathway are in development. This review
      describes the structure of the FGF signaling pathway, delineates its dual roles
      in angiogenesis and proliferation in NSCLC, evaluates FGF ligand and receptor
      expression as prognostic biomarkers in NSCLC, and discusses the development of
      FGF pathway inhibitors for the treatment of lung malignancies.

PMID- 21959110
TI  - Hypoxia-inducible factors in OSCC.
AB  - Oral squamous cell carcinoma (OSCC) is a characteristic locally aggressive tumor
      in which hypoxia levels are very high, causing a low response to chemotherapy and
      providing basic resistance to anticancer drugs. Tumoral hypoxia directly depends
      on hypoxia-inducible factors (HIF). The goal of this paper is to describe HIF
      basic biology and tumor cells (HIF-1alpha, mainly), analyzing the effects of its
      expression in OSCC, study its relation with other molecules such as nitric oxide
      (NO), carbonic anhydrase (CA) or VEGF and assess the possibility of its
      manipulation as a therapeutic target.

PMID- 21959111
TI  - Nitidine Chloride inhibits breast cancer cells migration and invasion by
      suppressing c-Src/FAK associated signaling pathway.
AB  - Nitidine is a benzophenanthridine alkaloid, which has been shown to have anti
      tumor properties. Here, we demonstrated that Nitidine Chloride (NC) could inhibit
      breast cancer cells migration and invasion both in vitro and in vivo. Meanwhile,
      the protrusion formation and partial proteolytic activity of MMP-9 and MMP-2 were
      attenuated by NC in a dose-dependent manner in MDA-MB-231 cells. Furthermore,
      addition NC to cells significantly decreases PDGF induced phosphorylation of c
      Src, FAK, MAPKs, activation of RhoA, Rac1 and AP-1 transcriptional activity.
      Taken together, our results indicate that NC could have potential as a novel anti
      metastasis drug to breast cancer.

PMID- 21959112
TI  - Perceptions and practices regarding use of personal listening devices among
      medical students in coastal south India.
AB  - Today's generation enjoys having music at their fingertips. This has led to an
      increase in the usage of personal listening devices (PLDs) over the past decade.
      There are significant concerns regarding harmful effects of PLD use. To find out
      the perception and practice of medical students regarding use of PLDs. Cross
      sectional study was carried out in Mangalore, Coastal south India. Data were
      collected using a 31 item semi structured questionnaire that was distributed
      among 570 medical students, of which 485 completed questionnaire were received
      giving an overall response rate of 86.14%. The study was approved by the
      departmental review board. STATISTICAL ANALYSIS USED: data were analyzed using
      SPSS Version 11.5, Chi-square test for association was used and P<0.05 was
      considered statistically significant. Of the total study participants, 83.1% of
      them used PLDs regularly, of whom 77.7% used it for more than 1 h a day. Overall,
      18.0% of the study population was aware that prolonged use of PLDs could be
      harmful to their health. Majority of the study subjects (72.4%) felt that the
      safe duration of listening to PLDs is 3 to 5 h. Among the subjects using PLDs >=
      1 h, 60.1% preferred ear phones and among those using PLDs <1 h, 44.1% preferred
      earphones. Overall, 12.4% experienced temporary hearing loss on usage of PLDs.
      The use of PLDs among the medical students is on the rise, and they should be
      made more aware of the harmful effects associated with its use.

PMID- 21959113
TI  - Evaluating the impact of wind turbine noise on health-related quality of life.
AB  - We report a cross-sectional study comparing the health-related quality of life
      (HRQOL) of individuals residing in the proximity of a wind farm to those residing
      in a demographically matched area sufficiently displaced from wind turbines. The
      study employed a nonequivalent comparison group posttest-only design. Self
      administered questionnaires, which included the brief version of the World Health
      Organization quality of life scale, were delivered to residents in two adjacent
      areas in semirural New Zealand. Participants were also asked to identify annoying
      noises, indicate their degree of noise sensitivity, and rate amenity.
      Statistically significant differences were noted in some HRQOL domain scores,
      with residents living within 2 km of a turbine installation reporting lower
      overall quality of life, physical quality of life, and environmental quality of
      life. Those exposed to turbine noise also reported significantly lower sleep
      quality, and rated their environment as less restful. Our data suggest that wind
      farm noise can negatively impact facets of HRQOL.

PMID- 21959114
TI  - Prevalence of hearing loss and accuracy of self-report among factory workers.
AB  - Noise represents one of the most common occupational health hazards. A Healthy
      People 2020 objective aims to reduce hearing loss in the noise-exposed public.
      The purpose of this study was to describe and compare perceived and measured
      hearing, and to determine the prevalence of hearing loss among a group of factory
      workers. Data collected as part of an intervention study promoting hearing
      protector use among workers at an automotive factory in the Midwest were used.
      Plant employees (n=2691) provided information regarding their perceived hearing
      ability, work role, and other demographics. The relationships among audiograms, a
      single-item measure of perceived hearing ability, and demographic data were
      explored using chi-square, McNemar's test, Mann-Whitney U-test, sensitivity, and
      specificity. The prevalence of hearing loss among noise-exposed factory workers
      was 42% (where hearing loss was defined as >25 dB loss at the OSHA-recommended
      frequencies of 2, 3, and 4 kHz in either ear). However, 76% of workers reported
      their hearing ability as excellent or good. The difference in perceived hearing
      ability was significant at each tested frequency between those with and without
      measured hearing loss. Self-reported hearing ability was poorly related to
      results of audiometry. Although this group of workers was employed in a regulated
      environment and served by a hearing conservation program, hearing loss was highly
      prevalent. These findings, together with national prevalence estimates, support
      the need for evaluation of hearing conservation programs and increased attention
      to the national goal of reducing adult hearing loss.

PMID- 21959115
TI  - Hearing impairment among workers exposed to excessive levels of noise in ginning
      industries.
AB  - Cotton ginning workers have a risk of hearing loss due to excessive noise levels
      at the workplace environment. In this study, estimates of typical sound levels
      prevailing at the workplace environment and its effects on hearing ability of the
      exposed workers were made among cotton ginning workers. Data on self-reported
      health status was collected by a questionnaire survey at 10 cotton ginning
      industries located at Jalgaon district of Maharashtra state, India. The cotton
      ginning workers were exposed to continuous noise levels between 89 and 106 dBA.
      The hearing ability of the subjects was accessed by pure tone audiometry. The
      results of audiometry show mild, moderate and moderately severe degree of hearing
      impairment among the cotton ginning workers. The data generated during the study
      show that hearing loss was significantly associated with period of exposure to
      the workplace noise (P <0.0001). The prevalence of audiometric hearing impairment
      defined as a threshold average greater than 25 dB hearing level was 96% for
      binaural low-frequency average, 97% for binaural mid frequency average and 94%
      for binaural high-frequency average in the cotton ginning workers. We recommend
      the compulsory use of personal protective equipment like ear plug by the cotton
      ginning workers at the workplace environment. A regular maintenance of ginning
      and pressing machineries will avoid the emission of excessive noise at the
      workplace environment of cotton gins. A regular periodic medical examination is
      necessary to measure the impact of workplace noise on the health of cotton
      ginning workers.

PMID- 21959116
TI  - Auditory sensitivity in opiate addicts with and without a history of noise
      exposure.
AB  - Several case reports suggest that some individuals are susceptible to hearing
      loss from opioids. A combination of noise and opium exposure is possible in
      either occupational setting such as military service or recreational settings.
      According to the Drug Enforcement Agency of the U.S. Department of Justice,
      prescriptions for opiate-based drugs have skyrocketed in the past decade. Since
      both opium and noise independently can cause hearing loss, it is important to
      know the prevalence of hearing loss among individuals who are exposed to opium or
      both opium and noise. The purpose of this research was to evaluate auditory
      sensitivity in individuals with a history of opium abuse and/or occupational or
      nonoccupational noise exposure. Twenty-three men who reported opiate abuse served
      as participants in the study. Four of the individuals reported no history of
      noise exposure, 12 reported hobby-related noise exposure, 7 reported occupational
      noise exposure including 2 who also reported hobby-related noise exposure. Fifty
      percent (2/4) of the individuals without any noise exposure had a hearing loss
      confirming previous reports that some of the population is vulnerable to the
      ototoxic effects of opioids. The percentage of population with hearing loss
      increased with hobby-related (58%) and occupational noise exposure (100%). Mixed
      MANOVA revealed a significant ear, frequency, and noise exposure interaction.
      Health professionals need to be aware of the possible ototoxic effects of
      opioids, since early detection of hearing loss from opium abuse may lead to
      cessation of abuse and further progression of hearing loss. The possibility that
      opium abuse may interact with noise exposure in determining auditory thresholds
      needs to be considered in noise exposed individuals who are addicted to opiates.
      Possible mechanisms of cochlear damage from opium abuse, possible reasons for
      individual susceptibility, and recommendations for future studies are presented
      in the article.

PMID- 21959117
TI  - Hearing status among aircraft maintenance personnel in a commercial airline
      company.
AB  - The aim was to study subjective and objective hearing loss in a population of
      aircraft maintenance workers and identify predictors. A total of 327 aircraft
      maintenance personnel answered a self-administered work environment questionnaire
      (response rate 76%) and underwent audiometric test. The mean values for the
      hearing threshold at 3, 4, and 6 kHz for the ear with the most hearing loss were
      compared with a Swedish population database of persons not occupationally exposed
      to noise. Equivalent noise exposure during a working day was measured.
      Relationships between subjective and objective hearing loss and possible
      predictors (age, years of employment, self-reported exposure to solvents, blood
      pressure, and psycho-social factors) were analyzed by multiple logistic
      regression. At younger ages (<40 years), aircraft maintenance workers had higher
      hearing thresholds (1-3 dB) compared to the reference group, but such a
      difference was not found in older employees. Relationships were found between age
      and objective hearing loss, and between exposure to solvents and reported
      subjective hearing loss. Equivalent noise exposure during working days were 70-91
      dB(A) with a maximal noise level of 119 dB(A). Aircraft maintenance workers are
      exposed to equivalent noise levels above the Swedish occupational standard,
      including some very high peak exposures. Younger employees have a higher age
      matched hearing threshold level compared with a reference group. Thus, there is a
      need for further preventive measures.

PMID- 21959118
TI  - Impact of albumin on drug delivery--new applications on the horizon.
AB  - Over the past decades, albumin has emerged as a versatile carrier for therapeutic
      and diagnostic agents, primarily for diagnosing and treating diabetes, cancer,
      rheumatoid arthritis and infectious diseases. Market approved products include
      fatty acid derivatives of human insulin or the glucagon-like-1 peptide
      (Levemir((r)) and Victoza((r))) for treating diabetes, the taxol albumin
      nanoparticle Abraxane((r)) for treating metastatic breast cancer which is also
      under clinical investigation in further tumor indications, and (99m)Tc-aggregated
      albumin (Nanocoll((r)) and Albures((r))) for diagnosing cancer and rheumatoid
      arthritis as well as for lymphoscintigraphy. In addition, an increasing number of
      albumin-based or albumin-binding drugs are in clinical trials such as antibody
      fusion proteins (MM-111) for treating HER2/neu positive breast cancer (phase I),
      a camelid albumin-binding nanobody anti-HSA-anti-TNF-alpha (ATN-103) in phase II
      studies for treating rheumatoid arthritis, an antidiabetic Exendin-4 analog bound
      to recombinant human albumin (phase I/II), a fluorescein-labeled albumin
      conjugate (AFL)-human serum albumin for visualizing the malignant borders of
      brain tumors for improved surgical resection, and finally an albumin-binding
      prodrug of doxorubicin (INNO-206) entering phase II studies against sarcoma and
      gastric cancer. In the preclinical setting, novel approaches include attaching
      peptides with high-affinity for albumin to antibody fragments, the exploitation
      of albumin-binding gadolinium contrast agents for magnetic resonance imaging, and
      physical or covalent attachment of antiviral, antibacterial, and anticancer drugs
      to albumin that are permanently or transiently attached to human serum albumin
      (HSA) or act as albumin-binding prodrugs. This review gives an overview of the
      expanding field of preclinical and clinical drug applications and developments
      that use albumin as a protein carrier to improve the pharmacokinetic profile of
      the drug or to target the drug to the pathogenic site addressing diseases with
      unmet medical needs.

PMID- 21959121
TI  - The subjective visual vertical:  validation of a simple test.
AB  - The study sought to provide norms for a simple test of visual perception of
      verticality (subjective visual vertical). The study was designed as a cohort
      study with a balanced design. The setting was the Rehabilitation Department of a
      University Hospital. Twenty-two healthy adults, of 23-58 years, 11 men (three
      left handed) and 11 women (three left handed) were enrolled. A luminous bar was
      displayed on a PC screen, and rotated in steps of 0.4 degrees  until the
      participant perceived it as vertical. A positive sign was attributed to a
      clockwise rotation of the bar. The detection threshold was set at the angle
      corresponding to a perceived vertical, which the participant then selected out of
      three subsequent alternatives (each at +0.4 or -0.4 degrees ). The participant's
      position (sitting vs. standing) and the preset angle of presentation (clockwise
      vs. counterclockwise) were balanced across sex. The constant or deviation error
      (dE, in degrees) and the absolute errors (aE, in degrees) were computed. An
      analysis of variance model tested the dependence of dE on sex, posture, age,
      handedness, and the preset angle. Both dE and aE were unrelated to sex, posture,
      handedness, and the preset angle, but were dependent on age (junior, <=43 years;
      senior, >43 years). The mean dE was -0.14 +/- 0.60 in the junior and 0.42 +/-
      0.64 in the senior group, respectively. The minimal real difference of the dE was
      0.75 and 0.25 in the junior and the senior group, respectively. The overall
      median aE was 0.4 (5th-95th percentile 0-1.2) in the junior and 0.8 (0.4-1.46) in
      the senior group, respectively. The whole test took no longer than 15 min in
      healthy participants, and 25 min in stroke patients. The test was applied to
      three subacute stroke patients with left hemiparesis, of whom two showed left
      spatial hemineglect. All three patients presented with a significant clockwise
      dE. This simple test appears to be valid for the routine assessment of spatial
      disorders in neurological impairments.

PMID- 21959122
TI  - Insurance and education predict long-term survival after orthotopic heart
      transplantation in the United States.
AB  - BACKGROUND: Insurance status and education are known to affect health outcomes.
      However, their importance in orthotopic heart transplantation (OHT) is unknown.
      The United Network for Organ Sharing (UNOS) database provides a large cohort of
      OHT recipients in which to evaluate the effect of insurance and education on
      survival. METHODS: UNOS data were retrospectively reviewed to identify adult
      primary OHT recipients (1997 to 2008). Patients were stratified by insurance at
      the time of transplantation (private/self-pay, Medicare, Medicaid, and other) and
      college education. All-cause mortality was examined using multivariable Cox
      proportional hazard regression incorporating 15 variables. Survival was modeled
      using the Kaplan-Meier method. RESULTS: Insurance for 20,676 patients was
      distributed as follows: private insurance/self-pay, 12,298 (59.5%); Medicare,
      5,227 (25.3%); Medicaid, 2,320 (11.2%); and "other" insurance, 831 (4.0%).
      Educational levels were recorded for 15,735 patients (76.1% of cohort): 7,738
      (49.2%) had a college degree. During 53 +/- 41 months of follow-up, 6,125
      patients (29.6%) died (6.7 deaths/100 patient-years). Survival differed by
      insurance and education. Medicare and Medicaid patients had 8.6% and 10.0% lower
      10-year survival, respectively, than private/self-pay patients. College-educated
      patients had 7.0% higher 10-year survival. On multivariable analysis, college
      education decreased mortality risk by 11%. Medicare and Medicaid increased
      mortality risk by 18% and 33%, respectively (p <= 0.001). CONCLUSIONS: Our study
      examining insurance and education in a large cohort of OHT patients found that
      long-term mortality after OHT is higher in Medicare/Medicaid patients and in
      those without a college education. This study points to potential differences in
      the care of OHT patients based on education and insurance status.

PMID- 21959124
TI  - Histologic assessment of perilesional skin in vesiculobullous diseases:  giving
      its due.

PMID- 21959123
TI  - Medical and psychosocial predictors of mechanical circulatory support device
      implantation and competing outcomes in the Waiting for a New Heart Study.
AB  - BACKGROUND: Medical and psychosocial factors are related to 1-year outcomes in
      the Waiting for a New Heart Study. With increased use of mechanical circulatory
      support devices (MCSD) over the course of the study, we can now evaluate these
      variables as predictors of MCSD in an extended follow-up. METHODS: Analyses
      focused on 313 MCSD-free patients (82% men; aged 53 +/- 11 years) newly listed
      for heart transplantation (HTx). Variables assessed at time of listing included
      psychosocial risk (depression, social isolation), quality of life, waiting list
      stress, and medical risk (Heart Failure Survival Score, pulmonary capillary wedge
      pressure). Cumulative incidence functions and cause-specific Cox models examined
      the association of medical and psychosocial risk (low: non-depressed and socially
      integrated; medium: depressed or socially isolated; high: depressed and socially
      isolated) with time until MCSD, considering covariates and competing outcomes
      (death, high-urgency transplantation [HU-HTx], elective HTx, and delisting due to
      clinical improvement or deterioration). RESULTS: Psychosocial risk groups were
      comparable regarding demographics, medical parameters, and quality of life, but
      differed in waiting list-related stressors. During follow-up (median, 326; range,
      5-1,849 days), 26 patients received MCSD, 53 died, 144 underwent HTx (103 in HU
      status), and 53 were delisted (15 deteriorated, 31 improved). Non-depressed and
      socially integrated patients did not require MCSD. Controlling for medical risk,
      psychosocial risk significantly contributed to MCSD, HU-HTx, and improvement;
      medical risk and female gender predicted death (p < 0.05). CONCLUSIONS:
      Psychosocial risk at time of listing affects the prognosis of HTx candidates
      beyond medical risk. Psychosocial interventions may help to stabilize patients'
      health.

PMID- 21959125
TI  - A study of educational underachievement in Indian children with epilepsy.
AB  - BACKGROUND: Epilepsy is a chronic disorder that significantly affects learning
      and behavior. Children with epilepsy are much more vulnerable for educational
      problems than with any other chronic illness. OBJECTIVES: The study was conducted
      to assess the extent of educational problems and factors associated with
      educational underachievement in Indian children with epilepsy. METHODS: It was a
      case control study and included 100 cases of 6-16 years age of epilepsy, 50
      healthy children (control A) and 50 children with persistent asthma (control B).
      Their demographic and disease variables were evaluated. The educational
      performance was assessed by using a predesigned semi structured open ended
      questionnaire to parents and by teacher's report. Psychological evaluation was
      done in first step by using a standard questionnaire, childhood psychopathology
      measurement schedule. In second step, those have shown poor educational
      performance or significant score in standard questionnaire underwent detailed
      psychiatric evaluation. RESULTS: Educational problems were reported in cases
      (36%), control A (2%) and control B (16%). Demographic or disease variables were
      not associated with educational problems in cases except that boys were more
      affected than girls. On psychiatric evaluation psychopathological illnesses (47%)
      like attention deficit hyperkinetic disorder, conduct disorder and depression
      were found to be commonly associated with poor educational performance (47%)
      followed by decreased learning opportunities (22.2%) and borderline intelligence
      (19.4%) in children with epilepsy. CONCLUSION: Educational problems are commoner
      in children with epilepsy than with asthma. Psychopathological problems are
      commonly associated with educational underachievement in children with epilepsy.
      Therefore periodic psychosocial assessment, counseling and support must be
      provided to improve the psychosocial adjustment in children with epilepsy.

PMID- 21959126
TI  - EEG characteristics predict subsequent epilepsy in children with febrile seizure.
AB  - The role of electroencephalography (EEG) in the work-up of febrile seizure (FS)
      remains controversial. We investigated the importance of EEG characteristics,
      especially the localizations of paroxysmal discharges, as predictors for
      subsequent epilepsy. Patients were referred from the outpatient department for
      EEG within 7-20 days after the seizure. EEGs were classified as paroxysmally
      abnormal based on the presence of spikes, sharp waves, or spike-wave complexes,
      whether focal or generalized, that were considered abnormal for age and state. Of
      119 patients with FS, 26 (21.8%) revealed paroxysmal abnormality on EEG and 9
      (7.6%) developed epilepsy. Of nine patients with later epilepsy, 6 (66.7%)
      revealed paroxysmal EEG abnormality. Of 26 patients with paroxysmal abnormality,
      6 (23.1%) developed epilepsy. Of 10 patients with generalized paroxysmal spike
      and wave activity, one (10%) developed epilepsy. Of seven patients with rolandic
      discharge (RD), two (28.5%) developed epilepsy. Of four patients with paroxysms
      in the frontal region, three (75%) developed epilepsy. Of five patients with
      paroxysms in the occipital region, none developed epilepsy. Compared with
      generalized EEG foci, the relative risk (RR) for patients with frontal EEG foci
      was 27.0. Patients with frontal EEG paroxysms had a significantly higher risk of
      developing epilepsy than those with paroxysms in other regions of EEG foci
      (p=0.035). These findings suggest that patients with FS presenting with frontal
      paroxysmal EEG abnormalities may be at risk for epilepsy. In patients with
      frontal paroxysmal EEG abnormalities, serial EEG should be performed, even though
      it does not contribute to treatment.

PMID- 21959127
TI  - Using the Alberta Infant Motor Scale to early identify very low-birth-weight
      infants with cystic periventricular leukomalacia.
AB  - We examined whether the Alberta Infant Motor Scale (AIMS) is able to identify
      very low-birth-weight (VLBW) preterm infants with cystic periventricular
      leukomalacia (PVL) as early as 6 months of corrected age. Longitudinal follow-up
      AIMS assessments were done at 6, 12, and 18 months old for 35 VLBW infants with
      cystic PVL (cPVL(+)), 70 VLBW infants without cystic PVL (cPVL(-)), and 76 term
      infants (healthy controls: HC). Corrected age was used for the preterm infants.
      The cPVL(+) group had significantly lower prone, supine and sitting subscales at
      age 6, 12, and 18 months than the cPVL(-) group (all p<0.05). The cPVL(-) group
      showed significantly lower supine, prone, sitting, and standing subscales than
      the HC group only at age 6 months. At age 6 months, the areas under the receiver
      operator curve used to discriminate the cPVL(+) infants from cPVL(-) infants were
      0.82+/-0.04 for prone, 0.93+/-0.02 for supine, 0.83+/-0.05 for sitting, and
      0.62+/-0.07 for standing. The AIMS may help early identify VLBW infants with
      cystic PVL at age 6 months old.

PMID- 21959128
TI  - Decreased benzodiazepine receptor and increased GABA level in cortical tubers in
      tuberous sclerosis complex.
AB  - PURPOSE: To elucidate the functional characteristics of cortical tubers that
      might be responsible for epilepsy in tuberous sclerosis complex (TSC), proton
      magnetic resonance spectroscopy ((1)H-MRS) and [123I] iomazenil (123I-IMZ) single
      photon emission computed tomography (SPECT) were performed. METHODS: (1)H-MRS
      using a clinical 3-tesla magnetic resonance imager was performed in four children
      with TSC and 10 age-and sex-matched healthy control subjects. A single voxel was
      set on the right parietal lobe in control subjects. In patients with TSC, a
      single voxel was set on the epileptogenic tuber in the parietal or temporal lobe,
      and another voxel was set on the contralateral normal-appearing brain region. N
      Acetylaspartate (NAA), myo-Inositol (mIns) and Glutamate (Glu) were analyzed
      using a conventional STEAM (Stimulated Echo Acquisition Mode) method. The
      concentration of gamma-aminobutyric acid (GABA) was quantified using MEGA-Point
      Resolved Spectroscopy (PRESS). Interictal 123I-IMZ SPECT was examined in all four
      patients with TSC. RESULTS: A significant decrease in the NAA concentration and
      significant increases in the mIns and GABA concentrations were detected in the
      cortical tubers of all 4 patients. No significant difference was observed in Glu
      concentrations. In all of the cortical tubers detected by magnetic resonance
      imaging, 123I-IMZ binding was significantly decreased. CONCLUSION:
      Epileptogenesis in TSC might be caused by decreased inhibition secondary to the
      decrease in GABA receptors in dysplastic neurons of cortical tubers. An increase
      in the GABA concentration may compensate for decreased inhibition.

PMID- 21959129
TI  - Clinical outcomes based on completeness of revascularisation in patients
      undergoing percutaneous coronary intervention: a meta-analysis of multivessel
      coronary artery disease studies.
AB  - AIMS: Most studies investigating completeness of revascularisation and outcomes
      for multivessel disease (MVD) patients are limited by small sample size. METHODS
      AND RESULTS: We searched PUBMED, Cochrane and EMBASE for studies comparing
      outcomes of MVD patients with complete revascularisation (CR) vs. incomplete
      revascularisation (IR) in the stent era. We identified nine studies that met our
      selection criteria. Compared to IR, patients undergoing CR had significantly
      lower risk of mortality (relative risk (RR): 0.82; 95% confidence interval (CI):
      0.68-0.99; p=0.05), non-fatal myocardial infarction (MI) (RR: 0.67; 95% CI: 0.53
      0.84; p <0.01) and subsequent coronary artery bypass graft surgery (CABG) (RR:
      0.70; 95% CI: 0.52-0.95; p=0.02) whereas no difference was noted in the incidence
      of repeat percutaneous coronary intervention (PCI) (RR: 0.87; 95% CI: 0.69-1.11;
      p=0.28). Average weighted follow up was approximately 29 months for mortality,
      subsequent CABG and Repeat PCI whereas it was 19 months for non-fatal MI. The
      results were similar after excluding the only RCT or the one study restricted to
      diabetics or the study restricted to drug-eluting stent use. CONCLUSIONS: In
      patients with multivessel coronary disease, complete revascularisation with PCI
      may be associated with better outcomes than incomplete revascularisation.

PMID- 21959130
TI  - Comparing error minimized extreme learning machines and support vector sequential
      feed-forward neural networks.
AB  - Recently, error minimized extreme learning machines (EM-ELMs) have been proposed
      as a simple and efficient approach to build single-hidden-layer feed-forward
      networks (SLFNs) sequentially. They add random hidden nodes one by one (or group
      by group) and update the output weights incrementally to minimize the sum-of
      squares error in the training set. Other very similar methods that also construct
      SLFNs sequentially had been reported earlier with the main difference that their
      hidden-layer weights are a subset of the data instead of being random. These
      approaches are referred to as support vector sequential feed-forward neural
      networks (SV-SFNNs), and they are a particular case of the sequential
      approximation with optimal coefficients and interacting frequencies (SAOCIF)
      method. In this paper, it is firstly shown that EM-ELMs can also be cast as a
      particular case of SAOCIF. In particular, EM-ELMs can easily be extended to test
      some number of random candidates at each step and select the best of them, as
      SAOCIF does. Moreover, it is demonstrated that the cost of the computation of the
      optimal output-layer weights in the originally proposed EM-ELMs can be improved
      if it is replaced by the one included in SAOCIF. Secondly, we present the results
      of an experimental study on 10 benchmark classification and 10 benchmark
      regression data sets, comparing EM-ELMs and SV-SFNNs, that was carried out under
      the same conditions for the two models. Although both models have the same
      (efficient) computational cost, a statistically significant improvement in
      generalization performance of SV-SFNNs vs. EM-ELMs was found in 12 out of the 20
      benchmark problems.

PMID- 21959131
TI  - SignalP 4.0: discriminating signal peptides from transmembrane regions.

PMID- 21959132
TI  - Sorting out sequencing data.

PMID- 21959133
TI  - Induced pluripotent stem cells for conserving endangered species?

PMID- 21959134
TI  - The proteomes of native and induced pluripotent stem cells.

PMID- 21959135
TI  - Cells see the light to bring signaling under control.

PMID- 21959136
TI  - Optical sectioning microscopy with planar or structured illumination.
AB  - A key requirement for performing three-dimensional (3D) imaging using optical
      microscopes is that they be capable of optical sectioning by distinguishing in
      focus signal from out-of-focus background. Common techniques for fluorescence
      optical sectioning are confocal laser scanning microscopy and two-photon
      microscopy. But there is increasing interest in alternative optical sectioning
      techniques, particularly for applications involving high speeds, large fields of
      view or long-term imaging. In this Review, I examine two such techniques, based
      on planar illumination or structured illumination. The goal is to describe the
      advantages and disadvantages of these techniques.

PMID- 21959137
TI  - Kawasaki disease and juvenile systemic lupus erythematosus.
AB  - Kawasaki disease (KD) is a common vasculitis in childhood. To the authors'
      knowledge, only one case of juvenile systemic lupus erythematosus (JSLE)-like
      onset mimicking KD and another case of KD and JSLE association have previously
      been described. However, the prevalence of this association of the two diseases
      was not reported. Therefore, over 27 consecutive years, 5419 patients were
      followed at the Pediatric Rheumatology Unit and 271 (5%) of them met the ACR
      classification criteria for JSLE. Two (0.7%) of them were female. These also had
      KD according to European League against Rheumatism / Paediatric Rheumatology
      European Society (EULAR/PReS) consensus criteria and are described in this
      report. One case was a 13-year-old who presented all six KD criteria.
      Echocardiogram showed pericardial effusion, dilatation and tortuosity of right
      and left coronary, and her symptoms promptly improved after treatment with
      intravenous immunoglobulin (IVIG). Lupus diagnosis was established a few days
      later. Another case was a 4-year-old who had also met all six KD criteria, with
      improvement after IVIG, and lupus diagnosis was made 1 year later. In conclusion,
      the frequency of the association between these two autoimmune diseases was rare.
      The occurrence of a second autoimmune systemic disease in a patient with a
      history of KD should also be considered. Furthermore, the initial presentation of
      lupus may mimic KD.

PMID- 21959138
TI  - Prospective assessment of C4d deposits on circulating cells and renal tissues in
      lupus nephritis: a pilot study.
AB  - Complement activation plays a key role in the pathogenesis of lupus nephritis
      (LN), a severe complication of systemic lupus erythematosus (SLE). We
      prospectively evaluated 15 LN subjects and two control groups: 13 non-SLE renal
      subjects (control A) and 239 SLE subjects without LN (control B). All had C4d
      levels on circulating erythrocytes (E-C4d), reticulocytes (R-C4d) and platelets
      (P-C4d) measured by flow cytometry, while C4d deposition in renal tissue was
      semiquantitatively assessed in LN subjects and control A using immunoperoxidase
      staining. Compared with control A, LN biopsies had higher glomerular-C4d scores
      (p = 0.003), which were associated with more frequent granular glomerular
      immunofluorescence staining and electron dense deposits (p < 0.001). Compared
      with control A and B groups, LN subjects had higher E-C4d (p = 0.002 and p =
      0.005) and R-C4d levels (p = 0.002 and p = 0.008), respectively. LN subjects were
      more likely to have P-C4d compared with control A (p = 0.016). In LN, only E-C4d
      correlated with National Institutes of Health (NIH) activity index (r = 0.55, p =
      0.04). In conclusion, LN biopsies showed frequent glomerular-C4d staining
      associated with immune complex deposits. LN subjects had higher E-C4d and R-C4d
      levels compared with both control groups. E-C4d levels also correlated with NIH
      activity index. These findings suggest a potential role of C4d on circulating
      cells as a biomarker for lupus nephritis.

PMID- 21959139
TI  - Incorporation of gypsum waste in ceramic block production: Proposal for a minimal
      battery of tests to evaluate technical and environmental viability of this
      recycling process.
AB  - Civil engineering-related construction and demolition debris is an important
      source of waste disposed of in municipal solid waste landfills. After clay
      materials, gypsum waste is the second largest contributor to the residential
      construction waste stream. As demand for sustainable building practices grows,
      interest in recovering gypsum waste from construction and demolition debris is
      increasing, but there is a lack of standardized tests to evaluate the technical
      and environmental viability of this solid waste recycling process. By recycling
      gypsum waste, natural deposits of gypsum might be conserved and high amounts of
      the waste by-product could be reused in the civil construction industry. In this
      context, this paper investigates a physical property (i.e., resistance to axial
      compression), the chemical composition and the ecotoxicological potential of
      ceramic blocks constructed with different proportions of clay, cement and gypsum
      waste, and assesses the feasibility of using a minimal battery of tests to
      evaluate the viability of this recycling process. Consideration of the results
      for the resistance to axial compression tests together with production costs
      revealed that the best formulation was 35% of plastic clay, 35% of non-plastic
      clay, 10% of Portland cement and 20% of gypsum waste, which showed a mean
      resistance of 4.64MPa. Energy dispersive X-ray spectrometry showed calcium and
      sulfur to be the main elements, while quartz, gypsum, ettringite and nacrite were
      the main crystalline compounds found in this formulation. Ecotoxicity tests
      showed that leachate from this formulation is weakly toxic toward daphnids and
      bacteria (EC(20%)=69.0 and 75.0, respectively), while for algae and fish the
      leachate samples were not toxic at the EC(50%) level. Overall, these results show
      that the addition of 20% of gypsum waste to the ceramic blocks could provide a
      viable substitute for clay in the ceramics industry and the tests applied in this
      study proved to be a useful tool for the technical and environmental evaluation
      of this recycling process, bacterial and daphnid tests being more sensitive than
      algae and fish tests.

PMID- 21959140
TI  - Comparing urban solid waste recycling from the viewpoint of urban metabolism
      based on physical input-output model: A case of Suzhou in China.
AB  - Investigating impacts of urban solid waste recycling on urban metabolism
      contributes to sustainable urban solid waste management and urban sustainability.
      Using a physical input-output model and scenario analysis, urban metabolism of
      Suzhou in 2015 is predicted and impacts of four categories of solid waste
      recycling on urban metabolism are illustrated: scrap tire recycling, food waste
      recycling, fly ash recycling and sludge recycling. Sludge recycling has positive
      effects on reducing all material flows. Thus, sludge recycling for biogas is
      regarded as an accepted method. Moreover, technical levels of scrap tire
      recycling and food waste recycling should be improved to produce positive effects
      on reducing more material flows. Fly ash recycling for cement production has
      negative effects on reducing all material flows except solid wastes. Thus, other
      fly ash utilization methods should be exploited. In addition, the utilization and
      treatment of secondary wastes from food waste recycling and sludge recycling
      should be concerned.

PMID- 21959141
TI  - Non invasive modified anterolateral approach in total hip arthroplasty.

PMID- 21959143
TI  - Tetracycline photolysis in natural waters: loss of antibacterial activity.
AB  - Previous work has shown that tetracycline undergoes direct photolysis in the
      presence of sunlight, with the decomposition rate highly dependent on conditions
      such as water hardness and pH. The purpose of this study was to examine the
      potential long-term significance of photoproducts formed when tetracycline
      undergoes photodegradation under a range of environmentally relevant conditions.
      Tetracycline was photolyzed in nine different natural and artificial water
      samples using simulated sunlight. The pH values of the samples ranged from 5 to
      9. Total hardness values (combined Ca(2+) and Mg(2+) concentrations) varied from
      30 to 450 ppm. Assays based on growth inhibition of two bacterial strains,
      Escherichia coli DH5alpha and Vibrio fischeri, were used to determine the
      antibacterial activity of tetracycline's photoproducts in these water samples. In
      all tested conditions, it was determined that the photoproducts retain no
      significant antibacterial activity; all observed growth inhibition was
      attributable to residual tetracycline. This suggests that tetracycline
      photoproducts formed under a wide range of pH and water hardness conditions will
      not contribute to the selection of antibiotic-resistant bacteria in environmental
      systems.

PMID- 21959144
TI  - Plant steroid hormones produced under Ni stress are involved in the regulation of
      metal uptake and oxidative stress in Brassica juncea L.
AB  - Brassinosteroids (BRs) are involved in the amelioration of various biotic and
      abiotic stresses. With an aim to explore the role of BRs under heavy metal
      stress, plants of Brassica juncea L. were grown in pots. The plants were
      subjected to various concentrations of Nickel metal (0.0, 0.2, 0.4 and 0.6 mM)
      and harvested on 60th day in order to observe the expression of these hormones.
      The isolated BRs from the leaves of Brassica plants characterized by GC-MS
      include 24-Epibrassinolide (24-EBL), Castasterone, Dolicholide and Typhasterole.
      The effect of isolated 24-EBL was studied on Ni metal uptake and antioxidative
      defense system in 60 d old plants of Brassica. It was observed that 24-EBL
      significantly increased the activities of stress ameliorating enzymes and lowered
      the metal uptake in plants. This is the first report in B. juncea L. plants
      showing the expression of BRs under metal treatments and effect of the isolated
      24-EBL on metal uptake and in oxidative stress management.

PMID- 21959145
TI  - PCDDs/PCDFs in ambient air (<1 fg m(-3)) - the CTDEP long term sampling (30 d)
      method.
AB  - The Connecticut Department of Environmental Protection (CTDEP) commenced
      monitoring for PCDDs/PCDFs (polychlorinated dibenzodioxins and polychlorinated
      dibenzofurans) in ambient air in 1987 and adopted the long term (30 d) sampling
      approach in 1993. The CTDEP method represents the first use of isotopically
      labeled PCDDs/PCDFs as field surrogates to monitor the behavior of native
      PCDDs/PCDFs present in actual ambient air samples. This feature first introduced
      in 1987 was later adopted by US EPA in revisions to sampling methods for
      PCDDs/PCDFs in ambient air (EPA Method TO9A) as well as development of EPA
      Reference Method 23 for measurement of PCDDs/PCFDs in stationary source
      emissions. Results are provided here for a total of twenty-three (23) samples
      (reported as pairs) representing twelve (12) 30 d sampling events conducted at a
      site located in metropolitan Hartford CT. Samples were collected in winter months
      during calendar years 2002-2008. PCDDs/PCDFs concentration data (pgm(-3)) are
      reported as both congener sums (Cl(4)-Cl(8)) and 2378-substitued congeners. Total
      PCDDs/PCDFs concentrations for these twelve (12) sampling events ranged from 0.68
      pg m(-3) (2003) to 4.18 pg m(-3) (2004) with a mean concentration of 2.04 pg m(
      3). Method performance was monitored through use of collocated samples, in field
      isotopically labeled compounds, isotopically labeled laboratory applied internal
      standards and field blank samples. Method performance consistently exceeded goals
      established in USEPA Method TO9A for these same parameters. Average recoveries of
      in field labeled PCDDs/PCDFs ranged from 97.5% to 104.2%. Average (mean)
      recoveries for each of the ten (10) isotopically labeled internal standards
      ranged from 77.0% ((13)C-OCDF) to 95.5% ((13)C-2,3,7,8-TCDF). Method precision
      defined as % RPD data for collocated sampler pairs ranged from 8% to 14% for
      PCDDs and from 5% to 12% for PCDFs. The mean RPD for all PCDDs/PCDFs combined is
      9.6%. Field monitoring results demonstrate method sensitivity for all PCDDs/PCDFs
      congeners and 2378-substituted congeners to be well below concentrations
      typically found for these compounds in ambient air (all reported data represent
      measured concentrations). Quantities (pg) found in field blanks represent the
      major determinant to achieving further enhancements in method sensitivity for
      selected congeners (OCDD<42 fg m(-3); 1,2,3,4,6,7,8-HpCDD<5.7 fg m(-3); and
      1,2,3,4,6,7,8-HpCDF<2.1 fg m(-3)). The CTDEP method represents a highly sensitive
      and reliable technique for monitoring of PCDDs/PCDFs congeners and other
      persistent organic pollutants (POPs) at ultra trace levels in ambient air (fg m(
      3)).

PMID- 21959146
TI  - Cathepsin B of Cynoglossus semilaevis: identification, expression, and activity
      analysis.
AB  - Cathepsin B (EC 3.4.22.1) is a member of the papain family cysteine protease and
      in mammals is known to be involved in protein degradation and other biological
      functions. However, very little is known about the function of cathepsin B in
      fish. In this study, we identified and analyzed a cathepsin B homologue (CsCatB)
      from tongue sole (Cynoglossus semilaevis, Pleuronectiformes), an economic fish
      species cultured in China. CsCatB is composed of 322 amino acid residues and
      shares 70-81.3% overall sequence identities with its counterpart in teleosts and
      humans. CsCatB possesses typical cathepsin B structural features including the
      propeptide region and the papain family cysteine protease domain, the latter
      containing the four catalytic residues (Q101, C107, H277, and N297) that are
      conserved in lower and higher vertebrates. Quantitative real time RT-PCR analysis
      showed that CsCatB expression occurred in multiple tissues and was positively
      regulated by bacterial infection and by immunization with a subunit vaccine.
      Recombinant CsCatB purified from Escherichia coli exhibited apparent protease
      activity, which was optimal at 35  degrees C and pH 5.5. In contrast, a mutant
      CsCatB bearing glutamic acid substitution at H277 was dramatically reduced in
      proteolytic activity. These results indicate that CsCatB is a biologically active
      protease that is likely to be involved in host immune response during bacterial
      infection and vaccination.

PMID- 21959147
TI  - Thermal unfolding studies of cold adapted uracil-DNA N-glycosylase (UNG) from
      Atlantic cod (Gadus morhua). A comparative study with human UNG.
AB  - Uracil-DNA N-glycosylase (UNG; EC 3.2.2.27) from Atlantic cod (cUNG) possesses
      cold adapted features like increased catalytic efficiency and reduced temperature
      optimum for activity compared to its warm-adapted homologue human UNG (hUNG).
      Here, we present the first thermal stability analysis of cUNG and hUNG by
      differential scanning calorimetry (DSC), and the results showed that cUNG is less
      stable than hUNG and unfolds at a melting temperature (T(m)) 9 degrees  lower
      than its warm-adapted homologue. In addition, an ion-pair (D183-K302) suggested
      to be crucial for global stability of hUNG was investigated by biochemical
      characterization and DSC of four mutants (cUNG G183D and cUNG G183D-R302K, hUNG
      D183G and hUNG D183G-K302R). The hUNG mutants with an expected disruption of the
      ion-pair showed a slight increase in stability with concomitant reduction in the
      enzyme activity, while the apparent introduction of the ion-pair in cUNG caused a
      reduction in the enzyme activity but no increase in stability. Because the
      mutants did not behave as expected, the phenomenon was further investigated by
      crystal structure determination. Indeed, the crystal structure of the hUNG D183G
      K302R mutant revealed that compensating interactions for the loss of the ion-pair
      were generated close to and in regions distant from the mutation site. In
      conclusion, the reduced stability of cUNG supports the suggested requirement of a
      flexible structure for improved activity at low temperatures. Furthermore, the
      lack of a direct correlation between enzyme activity and global stability of the
      mutants supports the significance of distributing locally flexible and/or rigid
      regions for modulation of enzyme activity.

PMID- 21959148
TI  - Piezoresistance behaviors of p-type 6H-SiC nanowires.
AB  - We reported, for the first time, the piezoresistance behaviors of single p-type
      6H-SiC nanowires. The results suggest that present p-type 6H-SiC nanowires could
      be an excellent candidate for the fabrication of robust and reliable stress
      sensors.

PMID- 21959149
TI  - Visual crowding.

PMID- 21959150
TI  - Bioluminescent aposematism in millipedes.

PMID- 21959151
TI  - Prestin links extrinsic tuning to neural excitation in the mammalian cochlea.

PMID- 21959152
TI  - Baby brain: training executive control in infancy.
AB  - A recent study shows that a relatively short period of cognitive training can
      improve infants' ability to sustain and flexibly deploy attention. Thus, it
      appears important aspects of cognition can be modified using 'brain-training'
      techniques at an early age.

PMID- 21959153
TI  - Plant sex chromosomes: a non-degenerated Y?
AB  - Animal Y chromosomes have undergone chromosome-wide degeneration in response to a
      lack of recombination, and ancient Ys contain few functional genes. Recent
      research suggests that plant Y chromosomes may evolve differently and retain most
      of their ancestral genes.

PMID- 21959154
TI  - Chromosome segregation: spindle mechanics come to life.
AB  - Chromosome segregation is a mechanical process, and the spindle generates, and is
      subject to, mechanical force. A recent study probes how the mechanical
      architecture of the spindle allows it to maintain mechanical integrity despite
      these forces.

PMID- 21959155
TI  - Tissue polarity: PCP inheritance ensured by selective mitotic endocytosis.
AB  - Recent findings report the selective internalization of core planar cell polarity
      components during mitosis followed by cell-non-autonomous polarized recycling.
      This novel mechanistic model explains how tissue polarity is inherited in
      daughter cells of proliferative tissue.

PMID- 21959156
TI  - Protein degradation: BAGging up the trash.
AB  - Cells efficiently uncover and degrade proteins that are misfolded. However, we
      know very little about what cells do to protect themselves from mislocalized
      proteins. A new study reveals a novel quality control pathway that recognizes and
      degrades secretory pathway proteins that have failed to target to the endoplasmic
      reticulum.

PMID- 21959157
TI  - Affective neuroscience: tracing the trace of fear.
AB  - The trace of fear has been elusive and difficult to discern in the human brain.
      Researchers have come up with a clever new way to track it down.

PMID- 21959158
TI  - Autophagy: cells SNARE selves.
AB  - Autophagosomes sequester cytosolic constituents and deliver this cargo to
      lysosomes for destruction. Two groups now report that autophagosome maturation
      requires homotypic membrane fusion catalyzed by SNARE proteins.

PMID- 21959159
TI  - It's all life history.

PMID- 21959160
TI  - On the programmed/non-programmed nature of ageing within the life history.
AB  - Understanding why and how senescence evolved is of great importance in
      investigating the multiple, complex mechanisms that influence the course of
      ageing in humans and other organisms. Compelling arguments eliminate the idea
      that death is generally programmed by genes for ageing, but there is still a
      widespread tendency to interpret data in terms of loosely defined 'age
      regulation', which does not usually make either evolutionary or mechanistic
      sense. This review critically addresses the role of natural selection in shaping
      ageing within the life history and examines the implications for research on
      genetic pathways that influence the life span. It is recognised that in
      exceptional circumstances the possibility exists for selection to favour limiting
      survival. In acknowledging that, at least in theory, ageing might occasionally be
      adaptive, however, the high barriers to validating actual instances of adaptive
      ageing are made clear.

PMID- 21959162
TI  - Ecological and evolutionary consequences of linked life-history stages in the
      sea.
AB  - Naturalists and scientists have been captivated by the diversity of marine larval
      forms since they were discovered following the advent of the microscope. Because
      they often bear little resemblance to adults, larvae were identified initially as
      new life forms, classified into different groups based on the similarity of their
      body plans and given new names that are still with us today. The radically
      different body plans and lifestyles of marine larvae and adults have led most
      investigators historically to study the two phases of complex life cycles in
      isolation. More recently, important ecological insights have sprung from taking a
      holistic view of marine life cycles. Meanwhile, the evolutionary (phenotypic and
      genetic) links among life-history phases remain less appreciated. In this review,
      our objective is to evaluate the evolutionary links within marine life cycles,
      and explore their ecological and evolutionary consequences. We provide a brief
      overview of marine life histories, discuss the phenotypic and genetic links
      between the two phases of the life cycle and pose challenges to advance our
      understanding of the evolutionary constraints acting on marine life histories.

PMID- 21959161
TI  - Primates and the evolution of long, slow life histories.
AB  - Primates are characterized by relatively late ages at first reproduction, long
      lives and low fertility. Together, these traits define a life-history of reduced
      reproductive effort. Understanding the optimal allocation of reproductive effort,
      and specifically reduced reproductive effort, has been one of the key problems
      motivating the development of life-history theory. Because of their unusual
      constellation of life-history traits, primates play an important role in the
      continued development of life-history theory. In this review, I present the
      evidence for the reduced reproductive effort life histories of primates and
      discuss the ways that such life-history tactics are understood in contemporary
      theory. Such tactics are particularly consistent with the predictions of
      stochastic demographic models, suggesting a key role for environmental
      variability in the evolution of primate life histories. The tendency for primates
      to specialize in high-quality, high-variability food items may make them
      particularly susceptible to environmental variability and explains their low
      reproductive-effort tactics. I discuss recent applications of life-history theory
      to human evolution and emphasize the continuity between models used to explain
      peculiarities of human reproduction and senescence with the long, slow life
      histories of primates more generally.

PMID- 21959163
TI  - The origins and evolution of vertebrate metamorphosis.
AB  - Metamorphosis, classically defined as a spectacular post-embryonic transition, is
      well exemplified by the transformation of a tadpole into a frog. It implies the
      appearance of new body parts (such as the limbs), the resorption of larval
      features (such as the tail) and the remodelling of many organs (such as the skin
      or the intestine). In vertebrates, metamorphosis has been well characterized in
      anuran amphibians, where thyroid hormones orchestrate the intricate and seemingly
      contradictory changes observed at the cellular and tissue levels. Thyroid
      hormones control a complex hierarchical cascade of target genes via binding to
      specific receptors, TRalpha and TRbeta, ligand-activated transcription factors
      belonging to the nuclear receptor superfamily. Metamorphosis is actually
      widespread in the vertebrates, though quite diverse in the way it manifests in a
      particular species. Furthermore, evolutionary and ecological variations of this
      key event, from paedomorphosis to direct development, provide an excellent
      illustration of how tinkering with a control pathway can lead to divergent life
      histories. The study of invertebrate chordates has also shed light on the origin
      of metamorphosis. The available data suggest that post-embryonic remodelling
      governed by thyroid hormones is an ancestral feature of chordates. According to
      this view, metamorphosis of the anurans is an extreme example of a widespread
      life history transition.

PMID- 21959164
TI  - Polyphenism in insects.
AB  - Polyphenism is the phenomenon where two or more distinct phenotypes are produced
      by the same genotype. Examples of polyphenism provide some of the most compelling
      systems for the study of epigenetics. Polyphenisms are a major reason for the
      success of the insects, allowing them to partition life history stages (with
      larvae dedicated to feeding and growth, and adults dedicated to reproduction and
      dispersal), to adopt different phenotypes that best suit predictable
      environmental changes (seasonal morphs), to cope with temporally heterogeneous
      environments (dispersal morphs), and to partition labour within social groups
      (the castes of eusocial insects). We survey the status of research on some of the
      best known examples of insect polyphenism, in each case considering the
      environmental cues that trigger shifts in phenotype, the neurochemical and
      hormonal pathways that mediate the transformation, the molecular genetic and
      epigenetic mechanisms involved in initiating and maintaining the polyphenism, and
      the adaptive and life-history significance of the phenomenon. We conclude by
      highlighting some of the common features of these examples and consider future
      avenues for research on polyphenism.

PMID- 21959166
TI  - Hormone signaling and phenotypic plasticity in nematode development and
      evolution.
AB  - Phenotypic plasticity refers to the ability of an organism to adopt different
      phenotypes depending on environmental conditions. In animals and plants, the
      progression of juvenile development and the formation of dormant stages are often
      associated with phenotypic plasticity, indicating the importance of phenotypic
      plasticity for life-history theory. Phenotypic plasticity has long been
      emphasized as a crucial principle in ecology and as facilitator of phenotypic
      evolution. In nematodes, several examples of phenotypic plasticity have been
      studied at the genetic and developmental level. In addition, the influence of
      different environmental factors has been investigated under laboratory
      conditions. These studies have provided detailed insight into the molecular basis
      of phenotypic plasticity and its ecological and evolutionary implications. Here,
      we review recent studies on the formation of dauer larvae in Caenorhabditis
      elegans, the evolution of nematode parasitism and the generation of a novel
      feeding trait in Pristionchus pacificus. These examples reveal a conserved and co
      opted role of an endocrine signaling module involving the steroid hormone
      dafachronic acid. We will discuss how hormone signaling might facilitate life
      history and morphological evolution.

PMID- 21959165
TI  - Coordinating growth and maturation - insights from Drosophila.
AB  - Adult body size in higher animals is dependent on the amount of growth that
      occurs during the juvenile stage. The duration of juvenile development,
      therefore, must be flexible and responsive to environmental conditions. When
      immature animals experience environmental stresses such as malnutrition or
      disease, maturation can be delayed until conditions improve and normal growth can
      resume. In contrast, when animals are raised under ideal conditions that promote
      rapid growth, internal checkpoints ensure that maturation does not occur until
      juvenile development is complete. Although the mechanisms that regulate growth
      and gate the onset of maturation have been investigated for decades, the emerging
      links between childhood obesity, early onset puberty, and adult metabolic disease
      have placed a new emphasis on this field. Remarkably, genetic studies in the
      fruit fly Drosophila melanogaster have shown that the central regulatory pathways
      that control growth and the timing of sexual maturation are conserved through
      evolution, and suggest that this aspect of animal life history is regulated by a
      common genetic architecture. This review focuses on these conserved mechanisms
      and highlights recent studies that explore how Drosophila coordinates
      developmental growth with environmental conditions.

PMID- 21959167
TI  - Macroparasite life histories.
AB  - Parasites and parasitism is common. Worm macroparasites have evolved life-history
      traits that allow them to successfully transmit between spatially and temporally
      separated patches of host resource and to survive within these environments.
      Macroparasites have common life-history strategies to achieve this, but these
      general themes are modified in a myriad of ways related to the specific biology
      of their hosts. Parasite life histories are also dynamic, responding to
      conditions inside and outside of hosts, and they continue to evolve, especially
      in response to our attempts to control them and the harm that they cause.

PMID- 21959168
TI  - Life histories of symbiotic rhizobia and mycorrhizal fungi.
AB  - Research on life history strategies of microbial symbionts is key to
      understanding the evolution of cooperation with hosts, but also their survival
      between hosts. Rhizobia are soil bacteria known for fixing nitrogen inside legume
      root nodules. Arbuscular mycorrhizal (AM) fungi are ubiquitous root symbionts
      that provide plants with nutrients and other benefits. Both kinds of symbionts
      employ strategies to reproduce during symbiosis using host resources; to
      repopulate the soil; to survive in the soil between hosts; and to find and infect
      new hosts. Here we focus on the fitness of the microbial symbionts and how
      interactions at each of these stages has shaped microbial life-history
      strategies. During symbiosis, microbial fitness could be increased by diverting
      more resources to individual reproduction, but that may trigger fitness-reducing
      host sanctions. To survive in the soil, symbionts employ sophisticated
      strategies, such as persister formation for rhizobia and reversal of spore
      germination by mycorrhizae. Interactions among symbionts, from rhizobial quorum
      sensing to fusion of genetically distinct fungal hyphae, increase adaptive
      plasticity. The evolutionary implications of these interactions and of microbial
      strategies to repopulate and survive in the soil are largely unexplored.

PMID- 21959169
TI  - Nuclear and genome dynamics in multinucleate ascomycete fungi.
AB  - Genetic variation between individuals is essential to evolution and adaptation.
      However, intra-organismic genetic variation also shapes the life histories of
      many organisms, including filamentous fungi. A single fungal syncytium can harbor
      thousands or millions of mobile and potentially genotypically different nuclei,
      each having the capacity to regenerate a new organism. Because the dispersal of
      asexual or sexual spores propagates individual nuclei in many of these species,
      selection acting at the level of nuclei creates the potential for competitive and
      cooperative genome dynamics. Recent work in Neurospora crassa and Sclerotinia
      sclerotiorum has illuminated how nuclear populations are coordinated for fungal
      growth and other behaviors and has revealed both molecular and physical
      mechanisms for preventing and policing inter-genomic conflict. Recent results
      from population-level genomic studies in a variety of filamentous fungi suggest
      that nuclear exchange between mycelia and recombination between heterospecific
      nuclei may be of more importance to fungal evolution, diversity and the emergence
      of newly virulent strains than has previously been recognized.

PMID- 21959171
TI  - The coronary collateral circulation: genetic and environmental determinants in
      experimental models and humans.
AB  - Obstruction of coronary arteries leads to an arteriogenic response. Pre-existent
      collateral networks enlarge, forming large conductance arteries with the
      capability to compensate for the loss of perfusion due to the occlusion.
      Interestingly, significant differences exist between patients regarding the
      capacity to develop such a collateral circulation. This heterogeneity in
      arteriogenic response is also found between and even within animal species and it
      strongly suggests that next to environmental factors, innate genetic factors play
      a key role. The present review focuses on this heterogeneity of genetic as well
      as non-genetic determinants of the coronary collateral circulation. This article
      is part of a Special Issue entitled "Coronary Blood Flow".

PMID- 21959170
TI  - Predicting fracture using 2D finite element modelling.
AB  - A decrease in bone density at the hip or spine has been shown to increase the
      risk of fracture. A limitation of the bone mineral density (BMD) measurement is
      that it provides only a measure of a bone sample's average density when projected
      onto a 2D surface. Effectively, what determines bone fracture is whether an
      applied load exceeds ultimate strength, with both bone tissue material properties
      (can be approximated through bone density), and geometry playing a role. The goal
      of this project was to use bone geometry and BMD obtained from radiographs and
      DXA measurements respectively to estimate fracture risk, using a two-dimensional
      finite element model (FEM) of the sagittal plane of lumbar vertebrae. The
      Canadian Multicentre Osteoporosis Study (CaMos) data was used for this study.
      There were 4194 men and women over the age of 50 years, with 786 having
      fractures. Each subject had BMD testing and radiographs of their lumbar
      vertebrae. A single two dimensional FEM of the first to fourth lumbar vertebra
      was automatically generated for each subject. Bone tissue stiffness was assigned
      based on the BMD of the individual vertebrae, and adjusted for patient age. Axial
      compression boundary conditions were applied with a force proportional to body
      mass. The resulting overall strain from the applied force was found. Men and
      women were analyzed separately. At baseline, the sensitivity of BMD to predict
      fragility fractures in women and men was 3.77% and 0.86%, while the sensitivity
      of FEM to predict fragility fractures for women and men was 10.8% and 11.3%. The
      FEM ROC curve demonstrated better performance compared to BMD. The relative risk
      of being considered at high fracture risk using FEM at baseline, was a better
      predictor of 5 year incident fragility fracture risk compared to BMD.

PMID- 21959172
TI  - Endothelin B receptor agonist, IRL-1620, reduces neurological damage following
      permanent middle cerebral artery occlusion in rats.
AB  - Endothelin and its receptors have long been considered therapeutic targets in the
      treatment of ischemic stroke. Recent studies indicate that ET(B) receptors may
      provide both vasodilatation and neuroprotection. The purpose of this study was to
      determine the effect of selectively activating the ET(B) receptors following
      permanent middle cerebral artery occlusion in rats. IRL-1620 [Suc-[Glu9,Ala11,15]
      Endothelin-1(8-12)], a highly selective ET(B) agonist, was used alone and in
      conjunction with BQ788, an ET(B) antagonist, to determine the role of ET(B)
      receptors in cerebral ischemia. Rats were assessed for neurological deficit and
      motor function, and their brains were evaluated to determine infarct area,
      oxidative stress parameters, and ET receptor protein levels. Animals treated with
      IRL-1620 showed significant improvement in all neurological and motor function
      tests when compared with both vehicle-treated and BQ788-treated middle cerebral
      artery occluded groups. In addition, there was a significant decrease in infarct
      volume 24h after occlusion in animals treated with IRL-1620 (24.47+/-4.37mm(3))
      versus the vehicle-treated group (153.23+/-32.18mm(3)). Blockade of ET(B)
      receptors by BQ788 followed by either vehicle or IRL-1620 treatment resulted in
      infarct volumes similar to those of rats treated with vehicle alone (163.51+/
      25.41 and 139.21+/-15.20mm(3), respectively). Lipid peroxidation, as measured by
      malondialdehyde, increased and antioxidants (superoxide dismutase and reduced
      glutathione) decreased following infarct. Treatment with IRL-1620 reversed these
      effects, indicating that ET(B) receptor activation reduces oxidative stress
      injury following ischemic stroke. Animals pretreated with BQ788 showed similar
      oxidative stress damage as those in the vehicle-treated group. No significant
      difference was observed in ET(B) receptor levels in any of the groups. The
      present study demonstrates that ET(B) receptor activation may be a novel
      neuroprotective therapy in the treatment of focal ischemic stroke.

PMID- 21959173
TI  - The effect of observed biological and non biological movements on action
      imitation: an fMRI study.
AB  - Past research has indicated that when individuals observe biological movements
      many areas in the observer's motor system become active. Nonetheless, recent
      behavioral evidence showed that observed movements can interfere with execution
      of incompatible movements, especially the biological ones. However, the
      hypothesis that the interference originates within a common neural network,
      encoding both movement observation and execution, and responding preferentially
      to biological movements, still awaits confirmation. To test this hypothesis, in
      the present fMRI study we compared patterns of activation obtained when
      participants executed finger-movements after having observed either a biological
      or a non biological model performing compatible (imitative) or incompatible (non
      imitative) movements. Moreover, we tested the possibility that imitative
      responses are influenced by the emotional facial expression (sad, neutral, angry)
      presented before the observed movement. Behaviorally, participants showed a
      marginally larger compatibility effect (compatible movements faster than
      incompatible movements) in the biological condition than in the non biological
      condition. In the imaging data, the interaction testing for areas more active
      when the observed model was biological (compared with non biological) and
      performed compatible movements (compared with incompatible movements), activated
      a network including the motor, premotor and parietal cortices. Notably, the
      interaction was significant for the neutral and sad facial expressions only. We
      showed that observing biological movements modulates the activation of motor
      related regions, by facilitating the execution of compatible movements and/or
      interfering with the execution of incompatible movements.

PMID- 21959174
TI  - Transient ischemia-induced paresis and complete paraplegia displayed distinct
      reactions of microglia and macrophages.
AB  - In this study, we perform a detailed analysis of the microglial and macrophage
      responses in a model of spinal cord ischemia and reperfusion (SCI/R) injury in
      Wistar rats. The rats underwent occlusion across the descending aorta for 13min,
      causing paraplegia or paresis of varying severity. They were divided into four
      groups based on neurological assessment: sham, mild paresis, moderate paresis,
      and severe (complete) paraplegia. To examine the origin of microglia and
      macrophages in the ischemic lesion, bone marrow from rats expressing green
      fluorescent protein (GFP) was transplanted into test subjects one month before
      performing SCI/R. Many GFP(+)/CD68(+) microglia and macrophages were present 7d
      after SCI/R. Resident (GFP(-)/Iba1(+)/CD68(-)) microglia and bone marrow-derived
      macrophages (BMDMs; GFP(+)/Iba1(+)/CD68(+)) colocalized in the mild group 7d
      after SCI/R. In the moderate group, BMDMs outnumbered resident microglia. A
      greater accumulation of BMDMs expressing insulin-like growth factor-1 (IGF-1) was
      observed in lesions in the severe group, relative to the moderate group. BMDMs in
      the severe group strongly expressed tumor necrosis factor alpha, interleukin
      1beta, and inducible nitric oxide synthase, in addition to IGF-1. A robust
      accumulation of BMDMs occupying the entire ischemic gray matter was observed only
      in the severe group. These results demonstrate that the magnitude of the
      microglial and BMDM responses varies considerably, and that it correlates with
      the severity of the neurological dysfunction. Remarkably, BMDMs appear to have a
      beneficial effect on the spinal cord in paresis. In contrast, BMDMs seem to
      exhibit both beneficial and harmful effects in severe paraplegia.

PMID- 21959175
TI  - Dopamine deficiency increases synchronized activity in the rat subthalamic
      nucleus.
AB  - Abnormal neuronal activity in the subthalamic nucleus (STN) plays a crucial role
      in the pathophysiology of Parkinson's disease (PD). In this study we investigated
      changes in rat STN neuronal activity after 28days following the injection of 6
      OHDA in the substantia nigra pars compacta (SNc). This drug provoked a lesion of
      SNc that induced a dopamine (DA) depletion assessed by changes in rotating
      capacity in response to apomorphine injection and by histological analysis. By
      means of extracellular recordings and waveshape spike sorting it was possible to
      analyze simultaneous spike trains and compute the crosscorrelations. Based on the
      analysis of the autocorrelograms we classified four types of firing patterns:
      regular (Poissonian-like), oscillatory (in the range 4-12Hz), bursty and cells
      characterized by a long refractoriness. The distribution of unit types in the
      control (n=61) and lesioned (n=83) groups was similar, as well as the firing
      rate. In 6-OHDA treated rats we observed a significant increase (from 26% to 48%)
      in the number of pairs with synchronous firing. These data suggest that the
      synchronous activity of STN cells, provoked by loss of DA cells in SNc, is likely
      to be among the most significant dysfunctions in the basal ganglia of
      Parkinsonian patients. We raise the hypothesis that in normal conditions, DA
      maintains a balance between funneling information via the hyperdirect cortico
      subthalamic pathway and parallel processing through the parallel cortico-basal
      ganglia-subthalamic pathways, both of which are necessary for selected motor
      behaviors. This article is part of a Special Issue entitled 'Neural Coding'.

PMID- 21959176
TI  - Genetic association between ADAM10 gene polymorphism and Alzheimer's disease in a
      Northern Han Chinese population.
AB  - The ADAM10 gene encodes a member of a disintegrin and metalloprotease family,
      which, after overexpression in Alzheimer's disease (AD), prevents amyloid
      pathology and improves long-term potentiation and memory. A common polymorphism
      (rs2305421) within ADAM10 has been recently associated with the risk of
      developing AD in Europeans. In order to assess the involvement of the ADAM10
      polymorphism in the risk of developing late-onset AD (LOAD), we analyzed the
      genotype and allele distributions of the ADAM10 (rs2305421) polymorphism in 788
      Northern Han Chinese subjects. The results revealed no significant differences in
      the distributions of allele or genotype between LOAD and control groups. However,
      when these data were stratified by the Apolipoprotein E (ApoE) epsilon4 status,
      in the subjects with ApoE epsilon4, there were significant differences in the
      allele (P=0.037) and genotype (P=0.035). Moreover, logistic regression analysis
      revealed that the rs2305421 polymorphism presented strong associations with LOAD
      in the recessive model (OR=0.611, 95% CI=0.408-0.931, P=0.023). This study
      suggests that the rs2305421 polymorphism in ADAM10 gene could modify the risk for
      LOAD in a Northern Han Chinese population.

PMID- 21959177
TI  - The CRH-R1 receptor mediates luteinizing hormone, prolactin, corticosterone and
      progesterone secretion induced by restraint stress in estrogen-primed rats.
AB  - Acute stress has been shown to modify hypothalamus-pituitary-gonadal (HPG) axis
      activity. Corticotropin-releasing hormone (CRH), the principal regulator of the
      hypothalamus-pituitary-adrenal (HPA) axis, has been implicated as a mediator of
      stress-induced effects on the reproductive axis. The role of the specific CRH
      receptor subtypes in this response is not completely understood. In the current
      study, we investigated the role of the CRH-R(1) receptor on luteinizing hormone
      (LH), follicle-stimulating hormone (FSH), prolactin (PRL), progesterone (P) and
      corticosterone (CT) secretion in stress-induced responses under the influence of
      estrogen (E(2)). Estrogen-primed ovariectomized rats (estradiol cypionate, 10 MUg
      sc) received an i.v. administration of antalarmin (0.1 or 1mg/kg), a selective
      CRH-R(1) antagonist, or vehicle before restraint stress for 40 min. Seven blood
      samples were collected from two experimental groups (one from 10:00 h to 14:00 h
      and the other from 10:00 h to 18:00 h). An increase of plasma LH induced by
      restraint acute-stress was followed by alteration of the secretion pattern in the
      estrogen-induced afternoon surge. In a similar manner, we observed a suppression
      of the afternoon surge in plasma FSH, a delay of E(2)-induced PRL secretion, and
      an increase in plasma P and CT. Antalarmin attenuated stress-induce LH increase,
      decreased CT and P secretion and blocked the stress effects on PRL secretion.
      These findings suggest that CRH-R(1) mediates, at least in part, the restraint
      stress effects on the HPA, PRL, and reproductive axes.

PMID- 21959178
TI  - Hesperidin ameliorates functional and histological outcome and reduces
      neuroinflammation in experimental stroke.
AB  - Incidence of stroke is considered to be a major cause of death throughout the
      world. The middle cerebral artery occlusion (MCAO) for 2h followed by 22h of
      reperfusion model was used in male Wistar rats to study the protection of stroke
      by hesperidin. Hesperidin administration (50mg/kg b.wt.) once daily for 15days
      has improved the infarct size, reduced the neurological deficits in terms of
      behaviors, and protected the elevated level of thiobarbituric acid reactive
      species (TBARS). A significantly depleted activity of antioxidant enzymes,
      glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT) and
      superoxide dismutase (SOD) and content of glutathione (GSH) in MCAO group were
      protected significantly in MCAO group pretreated with hesperidin. Moreover,
      inflammatory mediators like TNF-alpha, IL-1beta levels, expression of iNOS and
      glial fibrillary acidic protein (GFAP) were significantly attenuated in H+MCAO
      group as compared to MCAO group. In conclusion, prophylactic treatment with
      hesperidin ameliorated the functional and histological outcomes with elevated
      endogenous antioxidants status as well as reduced induction of proinflammatory
      cytokines in MCA occluded rat. We theorized that hesperidin is among the
      pharmacological agents that reduce free radicals and its associated inflammation
      and have been found to limit the extent of brain damage following stroke.

PMID- 21959179
TI  - Three-year clinical event rates in different age groups after contemporary
      percutaneous coronary intervention.
AB  - AIMS: As the global population ages, elderly patients will form an increasing
      proportion of those undergoing percutaneous coronary intervention (PCI). We
      investigated the safety and efficacy of bare metal stents (BMS) and DES in all
      patients undergoing PCI at our institution, stratified by age. METHODS AND
      RESULTS: We investigated three sequential groups of consecutive patients treated
      exclusively with BMS (n=2,194; January 2000 to April 2002), sirolimus-eluting
      stents (SES, n=834; April 2002 to February 2003) and paclitaxel-eluting stents
      (PES, n=2,841; February 2003 to December 2005). The primary endpoint was all
      cause mortality. Secondary endpoints included target vessel revascularisation
      (TVR) and composite major adverse cardiac events (MACE, defined as all-cause
      death, any nonfatal myocardial infarction or TVR). Patients were followed up for
      a median of 1,366 days. Patients were stratified into equal quintiles based on
      age (<51.8, 51.8-58.4, 58.4-65.4, 65.4-73.0 and >73.0 years). All-cause mortality
      was significantly higher in the eldest two groups, while TVR rates were similar
      across all age groups. DES were associated with reductions in TVR and MACE and a
      trend towards reduced mortality in all age groups. CONCLUSIONS: DES are safe and
      effective when compared to BMS, irrespective of age.

PMID- 21959180
TI  - Cross-cultural comparisons of medicinal floras--what are the implications for
      bioprospecting?

PMID- 21959181
TI  - Fructus panax ginseng extract promotes hair regeneration in C57BL/6 mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Radix panax ginseng (Panax ginseng C.A. Meyer,
      Araliaceae, RPG) has been documented to possess hair growth activity and widely
      used to treat alopecia, while no report has been issued to date on the effect of
      Fructus panax ginseng (FPG) on hair regeneration. MATERIALS AND METHODS: To
      investigate the effects of FPG extract on the proliferation of human hair dermal
      papilla cells (DPCs) and on the promotion of hair regeneration in C57BL6 mice,
      cell proliferation was evaluated in cultured DPC by 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyl tetrazolium bromide (MTT) and measured the expressions of Bcl-2 and
      Bax by immunoblot assay. We also compared the effects of topical FPG extract (1
      and 10 mg/ml, 100 MUl/d) with the effects of minoxidil as a positive control (5%,
      100 MUl/d) or vehicle control (30% ethanol) on the depilation-induced hair
      cycling in 7 week-old-C57BL/6 mice. RESULTS: FPG extract significantly increased
      the proliferation of DPCs in dose and time dependent manners (P<0.05, P<0.01 and
      P<0.001). FPG extract also enhanced Bcl-2 expression and decreased Bax expression
      compared with control (P<0.01). Moreover, significant elongations of anagen phase
      during hair cycle after application of FPG were evaluated by photographical and
      histological observations. CONCLUSIONS: FPG extract improves the cell
      proliferation of human DPCs through anti apoptotic activation. Topical
      administration of FPG extract might have hair regeneration activity for the
      treatment of hair loss.

PMID- 21959182
TI  - Can a Strychnos species be used as antiulcer agent? Ulcer healing action from
      alkaloid fraction of Strychnos pseudoquina St. Hil. (Loganiaceae).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Strychnos pseudoquina St. Hil. (Loganiaceae) is
      one Brazilian native medicinal species described in the first edition of the
      Brazilian Official Pharmacopoeia in 1929. This medicinal plant, popularly known
      as "quina-quina", "quina-branca" or "casca aromatica was very commonly used in
      folk medicine in tea form obtained from the bark and/or leaves as tonic,
      antipyretic, antimalarial and mainly against diseases of the liver, spleen and
      stomach. AIM OF THE STUDY: Previous study already characterized the
      gastroprotective action of this species The aim of the present study is to
      elucidate the mechanism of the healing process mediated by the methanolic extract
      (ME) and their enriched alkaloid fraction (EAF) from Strychnos pseudoquina in
      chronic gastric ulceration induced by 5% acetic acid in rats, an experimental
      model that accurately reflects human gastrointestinal disease. MATERIAL AND
      METHODS: The ME and EAF was administered orally in a single dose (based on
      previously study of dose-response curve) for 14 days after chronic ulceration was
      induced in rats. The healing effect of ME and EAF was evaluated by macroscopic
      and morphometric analyses, immunohistochemical assay (PCNA and SOD) and anti
      Helicobacter pylori effect was evaluated by in vitro assay. RESULTS: Our results
      demonstrated that EAF significantly reduced border internal (42%) and external
      (38%) lesion area (mm(2)) by macroscopic analyses (P<0.05). Animals treated with
      EAF stimulated some proliferative factors by increasing the height of epithelial
      regenerative area and the expression of PCNA-positive nuclei. The number of
      vessels in gastric mucosa of rats treated with EAF reveals an expressive increase
      (4 times more than vehicle treatment) of vessels that stimulate cells
      proliferation in the healing region. These results suggest that the recovery of
      vascularization of the ulcerated area is involved in the healing action of
      alkaloid fraction of Strychnos pseudoquina. The MIC (minimum inhibitory
      concentration) of 75 MUg/ml from EAF showed an effective in vitro anti
      Helicobacter pylori action of this fraction. EAF also was quite effective in the
      process of SOD release that is an important protective factor against bacterial
      agents. The efficacy of EAF was accomplished safely without presenting any
      alteration of toxicological parameters during 14 day of treatment. CONCLUSIONS:
      The expressive gastric healing effect by increasing cellular proliferation
      together with expression of SOD activity and antibacterial action against
      Helicobacter pylori confirm the efficacy of this species in heal gastric mucosa
      and these results are a important contribution to the knowledge of a crude drug
      presents at the Brazilian Official Pharmacopoeia since 1929.

PMID- 21959183
TI  - Effectiveness of Vernonia scorpioides ethanolic extract against skin inflammatory
      processes.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Vernonia scorpioides (Asteraceae) is a native
      Brazilian medicinal plant that is commonly used to treat skin disorders.
      Considering the traditional use of Vernonia scorpioides and the lack of
      information about its pharmacological properties, we investigated the topical
      anti-inflammatory effect of the ethanolic extract of Vernonia scorpioides (EEVS)
      on acute and chronic cutaneous inflammation models in mouse. MATERIALS AND
      METHODS: The topical anti-inflammatory effect of EEVS was evaluated against acute
      models (12-O-tetradecanoylphorbol acetate (TPA)- and arachidonic acid (AA)
      induced mouse ear oedema) and chronic models (multiple applications of croton
      oil). RESULTS: The EEVS caused a dose-related inhibition of oedema in both the
      TPA- and AA-induced acute models (DI(50)=0.24 and 0.68 mg/ear with an inhibition
      of 80 +/- 5% and 65 +/- 5%, respectively, for 1mg/ear). In addition, the TPA
      induced increase in myeloperoxidase activity (MPO) in the ear was reduced (77 +/-
      8%) by the topical application of EEVS. In the chronic model, the EEVS reduced
      all parameters evaluated: oedema formation (31 +/- 2%), epidermal
      hyperproliferation (histology) and MPO (25 +/- 10%). However, the topical
      treatment of EEVS had no effect on N-acetyl-beta-d-glucosaminidase activity. The
      EEVS effectively interfered in the ear oedema on the delayed-type
      hypersensitivity reaction induced by oxazolone. The topical treatment with EEVS
      performed on both phases or only on the elicitation phase caused the inhibition
      of the ear oedema-induced by oxazolone in 42.9% and 63.4%, respectively, when
      compared to control animals (sensitized and challenged). CONCLUSIONS: The results
      suggest that EEVS is effective as a topical anti-inflammatory agent in acute and
      chronic inflammatory processes and that its action is markedly influenced by the
      inhibition of neutrophil migration into inflamed tissue as well as by epidermal
      hyperproliferation.

PMID- 21959184
TI  - Gastrointestial and respiratory activities of Acacia leucophloea.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The barks of Acacia leucophloea (Fabaceae) are
      used in Pakistan traditional medicine as an astringent, a bitter, a thermogenic,
      a styptic, a preventive of infections, an anthelmintic, a vulnery, a demulcent,
      an expectorant, an antipyretic, an antidote for snake bites and in the treatment
      of bronchitis, cough, vomiting, wounds, ulcers, diarrhea, dysentery, internal and
      external hemorrhages, dental caries, stomatitis, and intermittent fevers and skin
      diseases. MATERIALS AND METHODS: A study was carried out for the possible
      elucidation of mechanisms justifying the traditional medicinal uses of A.
      leucophloea (Fabaceae) in gastrointestinal and respiratory diseases. In vitro
      experiments were carried out over isolated rabbit jejunum and guinea-pig ileum in
      order to determine spasmolytic and bronchorelaxant activities, while in vivo
      studies were conducted in mice for antidiarrheal properties. RESULTS: A methanol
      crude extract of barks of the plant caused a concentration-dependent relaxation
      (0.1-3 mg/ml) of isolated rabbit jejunum preparations in a pattern similar to
      that of nifedipine and dicyclomine, suggesting a Ca(2+) channel-blocking
      mechanism in addition to an anticholinergic effect. In guinea-pig ileum the
      extract caused a parallel shift in the Ach-curves without suppression of maximum
      contractile response, followed by a non-parallel shift with the suppression of
      maximum contractile response at higher concentration similar to that caused by
      dicyclomine. Moreover, in rabbit trachea, it also caused the relaxation of
      carbachol (1 MUM) and high K(+)-induced contractions at a dose ranging between
      0.1578 and 0.734 mg/ml and 0.46-0.94 mg/ml, respectively. These findings indicate
      that the extract possesses spasmolytic and bronchodilator activities, mediated
      possibly through blockade of Ca(2+) channels, thus justifying its medicinal use
      in diarrhea and asthma. Acacia leucophloea methanol extract exhibited dose
      dependent (100-500 mg/ml) protective effect against castor oil induced diarrhea.
      CONCLUSIONS: The data obtained contribute to the validation of the traditional
      use of Acacia leucophloea bark in treating gastrointestinal and respiratory
      disorders, providing an hypothesis on the possible mechanisms of action.

PMID- 21959185
TI  - Effective NH2-grafting on attapulgite surfaces for adsorption of reactive dyes.
AB  - The amine moiety has an important function in many applications, including,
      adsorption, catalysis, electrochemistry, chromatography, and nanocomposite
      materials. We developed an effective adsorbent for aqueous reactive dye removal
      by modifying attapulgite with an amino-terminated organosilicon (3
      aminopropyltriethoxysilane, APTES). Surface properties of the APTES-modified
      attapulgite were characterized by the Fourier transform infrared spectroscopy
      (FTIR), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and
      nitrogen adsorption-desorption. We evaluated the impact of solvent, APTES
      concentration, water volume, reaction time, and temperature on the surface
      modification. NH(2)-attapulgite was used to remove reactive dyes in aqueous
      solution and showed very high adsorption rates of 99.32%, 99.67%, and 96.42% for
      Reactive Red 3BS, Reactive Blue KE-R and Reactive Black GR, respectively. These
      powerful dye removal effects were attributed to strong electrostatic interactions
      between reactive dyes and the grafted NH(2) groups.

PMID- 21959186
TI  - Cr(VI) photocatalytic reduction: effects of simultaneous organics oxidation and
      of gold nanoparticles photodeposition on TiO2.
AB  - Commercial TiO(2) samples with different phase composition and surface area were
      tested as photocatalysts in the photoinduced reduction of Cr(VI) in aqueous
      suspensions at pH 3.7 under UV-visible light irradiation. This reaction was also
      coupled with the simultaneous photocatalytic oxidation of the pollutant azo dye
      Acid Orange 8 (AO8) and of formic acid, acting as hole scavengers. The co
      presence of oxidizable and reducible species ensured better separation of
      photogenerated charge carriers, resulting in a higher rate of both organics'
      oxidation and Cr(VI) reduction, especially in the case of high surface area
      anatase TiO(2), having the strongest affinity for Cr(VI) and AO8, as demonstrated
      by competitive adsorption tests. The effects on Cr(VI) photocatalytic reduction
      of gold nanoparticles photodeposited on TiO(2) and of the Au loading were also
      investigated, aiming at ascertaining if this noble metal plays a role in the
      electron transfer processes involved in Cr(VI) reduction.

PMID- 21959187
TI  - The effect of humic acids on the reverse osmosis treatment of hazardous landfill
      leachate.
AB  - This study deals with the treatment of hazardous waste landfill leachate with the
      help of reverse osmosis. The landfill is located in an abandoned brown coal pit
      in northern Bohemia. The leachate contained 7.2 g/L of dissolved inorganic salts.
      Among other contaminants were heavy metals, arsenic, ammonia nitrogen and
      associated organic pollutants, especially chlorinated compounds. A mobile
      membrane unit (LAB M30) equipped with a spiral wound element (FILMTEC SW30-4040),
      with a membrane area equaling 7.4 m2 was used for the pilot plant experiments.
      All experiments were carried out in batch mode. 94% conversion of the input
      stream into the permeate was achieved by use of a two-stage arrangement. Removal
      efficiencies of the monitored contaminants in the feed ranged from 94% for
      ammonia nitrogen to 99% for the two-valent ions. Removal efficiency for total
      dissolved solids was 99.3% on average. Due to varying levels of humic acids in
      the leachate throughout the year, fouling experiments were performed to
      investigate the separation process under different conditions than those used in
      the pilot plant. Leachates containing different concentrations of added humic
      acids were separated using a thin film composite on a propylene membrane. The
      added humic acids were obtained from samples of contaminated oxihumolite.

PMID- 21959188
TI  - Behavioural sensitivity of a key Southern Ocean species (Antarctic krill,
      Euphausia superba) to p,p'-DDE exposure.
AB  - Persistent organic pollutants (POPs) have been frequently measured throughout the
      Southern Ocean food web for which little information is available to assess the
      potential risks of POP exposure. The current study evaluated the toxicological
      sensitivity of a key Southern Ocean species, Antarctic krill, to aqueous exposure
      of p,p'-dichlorodiphenyl dichloroethylene (p,p'-DDE). Behavioural endpoints were
      used as indicators of sublethal toxicity. Immediate behavioural responses
      (partial immobility and tail flicking) most likely reflect neurotoxicity, while
      the p,p'-DDE body residue causing a median level of sublethal toxicity in
      Antarctic krill following 96h exposure (IEC50(sublethal toxicity)=3.9+/
      0.21mmol/kg lipid weight) is comparable to those known to cause sublethal
      narcosis in temperate aquatic species. Critical body residues (CBRs) were more
      reproducible across tests than effective seawater concentrations. These findings
      support the concept of the CBR approach, that effective tissue residues are
      comparable across species and geographical ranges despite differences in
      environmental factors.

PMID- 21959189
TI  - A new quantitative structure-property relationship model to predict
      bioconcentration factors of polychlorinated biphenyls (PCBs) in fishes using E
      state index and topological descriptors.
AB  - A quantitative structure-property relationship (QSPR) study for predicting the
      logarithm of bioconcentration factors (LogBCF) of polychlorinated biphenyls
      (PCBs) is presented in this work. For this, the descriptors were obtained using
      only the Simplified Molecular Input Line Entry System (SMILES) strings in the
      free web server Parameter Client. The model was built using the Partial Least
      Squares (PLS) regression method. The best model presented five descriptors (one E
      state index and four topological descriptors) and a high quality for fit,
      internal, and external predictions. The leave-N-out (LNO) cross validation and
      the y-randomization test showed the model is robust and has no shown chance
      correlation. With a second test set, the model was compared to other models and
      presented a root mean square error (RMSE) very close to the best model. The
      mechanistic interpretation was corroborated by other works in the literature and
      by the descriptors' theory. Thus, the results meet the five Organization for
      Economic Co-operation and Development (OECD) principles for validation of QSA(P)R
      models, and it is expected the model can effectively predict the BCF values in
      fishes of the PCB congeners without highly reliable experimental BCF.

PMID- 21959190
TI  - Intramural esophageal dissection in a young man with eosinophilic esophagitis.
AB  - Intramural esophageal dissection is a rare disorder that should be considered in
      patients presenting with chest pain, dysphagia, and hematemesis. Although most
      commonly occurring in elderly women with impaired coagulation, esophageal
      dissection has also been observed in other demographics including in those with
      eosinophilic esophagitis. In our report, we present the case of a 19-year-old man
      who was found to have an intramural esophageal dissection in the setting of
      undiagnosed eosinophilic esophagitis. There have been multiple, proposed
      management strategies; however, we implemented a nonoperative approach and
      obtained successful results. Intramural esophageal dissection is an important
      diagnosis for thoracic surgeons to be aware of as these patients often present as
      surgical emergencies, but often do not require an acute surgical intervention.

PMID- 21959191
TI  - Surgically treatable pulmonary arteriovenous fistula.
AB  - Arteriovenous fistuli are congenital malformations. Usually symptoms depend on
      size of the lesion. Lesions smaller than 2 cm are often asymptomatic. The most
      common symptoms are dyspnea, palpitation and fatigue. Cyanosis is indicative of
      right to left shunt. Helical computed tomography (CT) scan is a helpful
      diagnostic tool in this case. Surgery is the treatment of choice in patients with
      isolated lesions. Embolization is a selective method in patients with multiple or
      bilateral lesions. The patient was a 13-year-old boy complaining of cyanosis of
      lips and nails as well as dyspnea for 5 years. Definite diagnosis of pulmonary
      arteriovenous malformation (PAVM) in the right middle lobe was based on CT
      angiography. The patient underwent a thoracotomy and lobectomy of the right
      middle lobe. After surgery cyanosis and dyspnea were completely resolved.

PMID- 21959192
TI  - Aorto-right ventricular fistula: a complication of aortic valve replacement.
AB  - The occurrence of aorto-right ventricular (aorto-RV) fistula after prosthetic
      aortic valve replacement is rare. Transthoracic echocardiography (TTE) with color
      flow Doppler, transesophageal echocardiography (TEE), or both may be required for
      diagnosis. A 42-year-old woman sought care for palpitations and dyspnea due to
      atrial flutter 2 weeks after prosthetic aortic valve replacement and graft
      replacement of the ascending aorta. TTE and TEE revealed left-to-right shunt due
      to aorto-RV fistula.

PMID- 21959193
TI  - Surgical treatment combined with NSAIDs in fibrodysplasia ossificans progressiva.
AB  - Fibrodysplasia ossificans progressiva (FOP) is a rare and disabling genetic
      disorder characterized by congenital malformation of the great toes and by
      progressive heterotopic ossification. There is no effective treatment.
      Conservative management is unsuccessful, and operation result in failure because
      new ectopic bone forms at the operative site. We report a 10-year-old boy with
      FOP who underwent surgical management combined with non-steroidal anti
      inflammatory drugs (NSAIDs).

PMID- 21959194
TI  - Isolated severe tricuspid regurgitation in a post pneumonectomy patient with
      chronic atrial fibrillation.
AB  - Severe primary tricuspid regurgitation is a rare entity, with most cases of
      tricuspid regurgitation being functional and secondary to pulmonary hypertension
      from left heart pathologies. We report an unusual case of a female patient with a
      history of left pneumonectomy and chronic atrial fibrillation many years earlier,
      and who subsequently developed tricuspid annular dilatation, resulting in severe
      isolated primary tricuspid regurgitation despite normal pulmonary artery
      pressures and left ventricular systolic function. She required multiple
      hospitalizations for right heart failure and continued to be NYHA class IV
      despite receiving maximal medical management. She finally underwent an isolated
      tricuspid valve ring annuloplasty, which gave her symptomatic relief.
      Postoperatively, she improved to NYHA class 1-II still with chronic atrial
      fibrillation and mild to moderate tricuspid regurgitation at the time of her
      death 9 years later from pneumonia.

PMID- 21959195
TI  - Benign metastasizing leiomyoma of the lung.
AB  - A 44-year-old woman was found to have an abnormal shadow on a chest X-ray during
      a regular health checkup, and visited our department. Chest computed tomography
      showed multiple nodular shadows in both lungs. The patient had no history of
      neoplasm except for myomectomy for uterine leiomyoma 6 years previously. Eighteen
      months later, the nodules showed a gradual increase in size, and video-assisted
      thoracoscopic biopsy of a nodule was performed. Histopathologically, the
      pulmonary nodule was composed of benign smooth muscle cells proliferating in
      fascicles, consistent with the diagnosis of benign metastasizing leiomyoma.
      Benign metastasizing leiomyoma is defined as a histologically benign uterine
      smooth muscle tumor that acts in a somewhat malignant fashion and produces benign
      metastases. Although it is a rare condition, it should be considered in
      asymptomatic women of reproductive age with a history of uterine leiomyoma, who
      present with solitary or multiple pulmonary nodules. Herein, we report a case of
      pulmonary benign metastasizing leiomyoma.

PMID- 21959196
TI  - Morgagni hernia presenting as a right middle lobe compression.
AB  - A 25-year-old woman with a history of chronic bronchitis since age 12 and 3-4
      previous episodes of pneumonia presented to the emergency room with cough and
      shortness of breath. A CT scan of her chest revealed findings consistent with
      Morgagni hernia with herniation of omental fat, causing near complete compressive
      atelectasis of the right middle lobe. The diaphragmatic defect was successfully
      treated with a laparoscopic repair. The patient was discharged home on the first
      postoperative day after tolerating regular diet.

PMID- 21959197
TI  - Operation for an infected thoracoabdominal aneurysm in a patient previously
      treated with an axillobifemoral bypass for an infected abdominal aortic
      prosthesis: a case report.
AB  - High operative mortality of infected thoracoabdominal aortic aneurysms (ITAA) is
      partly attributable to ischemic injury during aortic clamping. A case is
      presented of an 88-year old man who was admitted with imminent rupture of an
      ITAA. Axillobifemoral bypass grafting had been performed after removal of an
      infected abdominal aortic prosthesis six years earlier. In situ graft replacement
      was performed during 70 minutes of aortic clamping just below the pulmonary hilum
      without causing any but transient renal ischemic injury. Since the infrarenal
      aorta was absent after previous removal of an infected aortic prosthesis, the
      axillobifemoral bypass provided sufficient blood supply to intestines, kidneys
      and spinal medulla via arterial collaterals. Blood supply was sufficient,
      although a previous rectosigmoid resection must have destroyed some of the
      collaterals and one iliac artery was chronically occluded. The most important
      message from this case is that an axillobifemoral bypass may prevent ischemic
      injury during operations for ITAA even when collateral circulation is reduced,
      possibly on the condition that backbleeding from end-organ arteries is prevented,
      and there is a pressurized aortic segment that can redistribute blood that
      arrives via arterial collaterals.

PMID- 21959198
TI  - Plasma hepatocyte growth factor elevation may be associated with early metastatic
      disease in primary lung cancer patients.
AB  - PURPOSE: Hepatocyte growth factor (HGF), a ligand of the c-met proto-oncogene,
      exhibits activating effects on human lung cancer both in vitro and in vivo.
      However, few studies have reported the correlations between concentration changes
      of blood HGF and postsurgical prognosis. METHODS: We evaluated whether surgery
      related blood HGF elevation has prognostic significance in patients with
      surgically resected non-small cell lung cancer. We examined blood HGF
      concentration, c-met expression, and postoperative prognosis of 25 cases of
      primary resected, non-small cell lung cancer. RESULTS: We divided the patients
      into 2 groups according to receiver operating characteristics curve analysis
      using 7.2 ng/mL as the cut-off value of blood HGF concentration. Survival curve
      analysis revealed that patients with a high level of HGF (over the cutoff value)
      exhibited a poor prognosis of metastatic disease, compared to those in the low
      level group after curative surgery (log rank test, P = 0.020; Wilcoxon test, P =
      0.016). CONCLUSION: Elevation of HGF in plasma may be an important prognostic
      factor for early metastatic disease in patients with primary lung cancer.
      Moreover, inhibition of HGF elevation may have therapeutic effects on early
      distant metastasis of lung cancer.

PMID- 21959199
TI  - Long-term results of lung decortication in patients with trapped lung secondary
      to coronary artery bypass grafting.
AB  - PURPOSE: To evaluate long-term results of decortications in patients with
      symptomatic restrictive pleurisy and trapped lung after coronary bypass grafting.
      METHODS: Twenty consecutive patients undergoing lung decortications for trapped
      lung after coronary bypass grafting were prospectively evaluated. Pulmonary
      function tests were used as objective criteria, and quality of life was assessed
      by the Medical Research Council dyspnea scale. A p value <0.05 was considered
      significant. RESULTS: Twenty patients, 3 women and 17 men, with a median age of
      59 years were evaluated. The median time interval between coronary bypass
      grafting and decortications was 9.3 months. The mean preoperative forced
      expiratory volume in one second and forced vital capacity were 63.8% +/- 7.4% and
      50.5% +/- 6.6% of the predicted value, respectively, and the improvement rates
      after decortications were 14.97% +/- 6.3% and 17.62% +/- 6.38%, respectively.
      Dyspnea scores improved after decortications (p <0.05). The median follow-up was
      25 months. After surgery, 3 patients developed superficial wound infections, and
      out of 7 patients with prolonged air leaks, 2 underwent re-operation. After
      surgery, one patient died on day 34 and another, after 3 years. CONCLUSION: Lung
      decortications, re-expanding the affected lung, ensures symptom remission and
      improves quality of life of patients with trapped lung after coronary bypass
      grafting in the long-term.

PMID- 21959200
TI  - Vitamin and mineral supplement users. Do they have healthy or unhealthy dietary
      behaviours?
AB  - It is unknown whether people use vitamin and mineral supplements (VMS) to
      compensate for unhealthy diets, or people whom already have a healthy diet use
      VMS. Therefore, this study aimed to examine correlates of VMS use and whether VMS
      users can be categorised into specific clusters based on dietary lifestyle
      variables. The data used came from the Swiss Food Panel questionnaire for 2010.
      The sample consisted of 6189 respondents, mean age was 54 years and 47.6% were
      males. Data was analysed with logistic regression analysis and hierarchical
      cluster analysis. The results revealed that for VMS use, gender, age, education,
      chronic illness, health consciousness, benefits of fortification, convenience
      food and sugar-sweetened beverage consumption were of importance. Cluster
      analysis revealed three clusters (1) healthy diet, (2) unhealthy diet and (3)
      modest diet. Compared to non-users a higher percentage of VMS users was
      categorised in the healthy cluster and a lower percentage in the unhealthy
      cluster. More VMS-users were categorised as having an unhealthy diet (31.4%) than
      having a healthy diet (20.6%). The results suggest that both hypotheses-VMS are
      used by people with unhealthy diets and by people who least need them-hold true
      meaning.

PMID- 21959201
TI  - Compulsive fantasy: proposed evidence of an under-reported syndrome through a
      systematic study of 90 self-identified non-normative fantasizers.
AB  - The experiences of 90 individuals who self-identify as "excessive" or
      "maladaptive" fantasizers are summarized in this report. Our sample consisted of
      75 female and 15 male participants, ranging in age from 18 to 63 who responded to
      online announcements. Participants completed a 14-question emailed survey
      requesting descriptions of their fantasy habits and causes of potential distress
      regarding fantasy. Results demonstrated that participants shared a number of
      remarkably specific behaviors and concerns regarding their engagement in
      extensive periods of highly-structured, immersive imaginative experiences,
      including the use of kinesthetic activity which accompanies the fantasies of 79%
      of participants. Participants reported distress stemming from three factors:
      difficulty in controlling the need or desire to engage in fantasizing; concern
      that the quantity of fantasizing interfered with actual relationships and
      endeavors; and intense shame and exhaustive efforts to keep this behavior hidden
      from others. It is hoped that this report will encourage interest in this elusive
      syndrome.

PMID- 21959202
TI  - Measuring consciousness: task accuracy and awareness as sigmoid functions of
      stimulus duration.
AB  - When consciousness is examined using subjective ratings, the extent to which
      processing is conscious or unconscious is often estimated by calculating task
      performance at the subjective threshold or by calculating the correlation between
      accuracy and awareness. However, both these methods have certain limitations. In
      the present article, we propose describing task accuracy and awareness as
      functions of stimulus intensity (thus obtaining an accuracy and an awareness
      curve) as suggested by Koch and Preuschoff (2007). The estimated lag between the
      curves describes how much stimulus intensity must increase for awareness to
      change proportionally as much as accuracy and the slopes of the curves are used
      to assess how fast accuracy and awareness increases and whether awareness is
      dichotomous. The method is successfully employed to assess consciousness
      characteristics on data from four different awareness scales.

PMID- 21959204
TI  - Phagocytosis and intracellular killing of heterogeneous vancomycin-intermediate
      Staphylococcus aureus strains.
AB  - Risk factors for invasive infections by heterogeneous vancomycin-intermediate
      Staphylococcus aureus (hVISA) may involve resistance to opsonophagocytosis and
      bacterial killing. hVISA strains typically have a thickened cell wall with
      altered peptidoglycan cross-linking. To determine whether hVISA may be endowed
      with an increased resistance to phagocytosis, this study assessed the
      characteristics of uptake and killing by granulocytes of three hVISA strains. All
      isolates were analysed by multilocus sequence typing and staphylococcal
      chromosome cassette mec typing. One of the strains belonged to the Hungarian
      meticillin-resistant S. aureus (MRSA) clone ST239-MRSA-III and the other two to
      the New York/Japan MRSA clone ST5-MRSA-II. In the presence of 10 % normal serum,
      the extent of phagocytosis and killing by blood granulocytes was equivalent for
      hVISA, MRSA and meticillin-sensitive S. aureus (MSSA) strains. Using granulocytes
      and serum from one patient who survived hVISA infection, the rate of phagocytosis
      and killing was also found to be comparable to that by control cells in the
      presence of 10 % serum. However, phagocytosis and killing of hVISA and MRSA (ATCC
      25923) strains by normal granulocytes was markedly decreased in the presence of
      low concentrations (1 and 2.5 %) of serum from the patient who survived hVISA
      infection compared with that found with normal human serum. These data suggest
      that hVISA and MRSA isolates may be more resistant to opsonophagocytosis and
      bacterial killing than MSSA isolates, at least in some cases.

PMID- 21959203
TI  - Loss of emotional insight in behavioral variant frontotemporal dementia or
      "frontal anosodiaphoria".
AB  - Loss of insight is a prominent clinical manifestation of behavioral variant
      frontotemporal dementia (bvFTD), but its characteristics are poorly understood.
      Twelve bvFTD patients were compared with 12 Alzheimer's disease (AD) patients on
      a structured insight interview of cognitive insight (awareness of having a
      disorder) and emotional insight (concern over having a disorder). Compared to the
      AD patients, the bvFTD patients were less aware and less concerned about their
      disorder, and they had less appreciation of its effects on themselves and on
      others. After corrective feedback ("updating"), the bvFTD patients were just as
      aware of their disorder as the AD patients but remained unconcerned and
      unappreciative of its effects. These findings suggest that lack of insight in
      bvFTD is not due to "anosognosia," or impaired cognitive and executive awareness
      of disease, but to "frontal anosodiaphoria," or lack of emotional concern over
      having bvFTD and its impact on themselves and others.

PMID- 21959205
TI  - Detection of Clostridium difficile toxin A/B genes by multiplex real-time PCR for
      the diagnosis of C. difficile infection.
AB  - Toxigenic Clostridium difficile culture is considered to be the standard
      diagnostic method for the detection of C. difficile infection (CDI). Culture
      methods are time-consuming and although enzyme immunoassay is rapid and easy to
      use, it has low sensitivity. In the present study, the AdvanSure CD real-time
      (RT)-PCR kit (LG Life Sciences) was evaluated for its ability to detect C.
      difficile toxin A (tcdA) and B (tcdB) genes, simultaneously. A total of 127 fresh
      diarrhoeal stool specimens, submitted to the clinical microbiology laboratory for
      C. difficile culture, were tested. C. difficile toxins and toxin genes were
      detected with a VIDAS C. difficile A&B (VIDAS-CDAB) enzyme-linked fluorescent
      immunoassay (ELFA) and the AdvanSure RT-PCR kit, respectively, according to the
      manufacturers' instructions. Their performance was compared with a standard
      toxigenic culture method as a reference. The sensitivity, specificity and
      positive and negative predictive values using the AdvanSure RT-PCR kit were 100
      %, 98.3 %, 84.6 % and 100 %, respectively, while those of the VIDAS-CDAB system
      were 63.6 %, 100 %, 100 % and 96.6 %, respectively. Four tcdA(+)/tcdB(+) strains
      of C. difficile were detected with the AdvanSure RT-PCR kit, which offers
      comparable sensitivity and specificity to the reference method with a turnaround
      time of ~3 hours.

PMID- 21959206
TI  - Increased expression of virulence attributes in oral Candida albicans isolates
      from human immunodeficiency virus-positive individuals.
AB  - Oral candidiasis caused by Candida albicans is recognized as one of the most
      frequent opportunistic infections in human immunodeficiency virus (HIV)-infected
      individuals. The overall severity and chronicity of oral candidiasis has been
      attributed exclusively to the HIV-induced immune deficiency of the affected
      individuals but not to the virulence factors of the pathogen, i.e. C. albicans.
      However, genotypic and phenotypic studies have suggested that HIV infection might
      be associated with preferential selection of C. albicans strains with altered
      virulence determinants, leading to colonization with Candida populations that are
      better able to cause disease in these immunologically compromised hosts. If this
      process of selection is indeed related to pathogenicity, it may be possible to
      measure alterations in different virulence factors produced by C. albicans in HIV
      infected patients. To evaluate this hypothesis, the present work was undertaken
      to determine simultaneously the expression of five virulence factors in oral C.
      albicans isolates colonizing and infecting HIV-positive and -negative
      individuals. The significance of genotypes in the pathogenesis of oral
      candidiasis was also elucidated. Oral swabs were collected from 335 consecutive
      individuals (210 HIV-positive and 125 HIV-negative). Virulence factors and
      genotypes were determined for all the C. albicans strains isolated. The results
      showed significantly increased expression of proteinase, phospholipase and
      haemolytic activities, as well as a greater ability to adhere, in isolates from
      HIV-positive compared with HIV-negative individuals (P<0.05). However, no
      significant differences in virulence factor expression in isolates colonizing or
      infecting HIV-positive individuals were seen. Genotype A was the predominant type
      (71.3 %); however, a relationship could not be established between the genotypes
      and the virulence factors, or with clinical infection. These data support the
      concept of preferential C. albicans strain selection with altered virulence
      determinants in HIV-infected individuals and emphasize the need for further
      molecular genetic linkage studies that could be helpful in dissecting the
      molecular causes of preferential strain selection, which may lead to new
      approaches for therapeutic intervention.

PMID- 21959207
TI  - Review of burn injuries secondary to home oxygen.
AB  - The use of long-term home oxygen therapy (HOT) has become increasingly common for
      treatment of chronic pulmonary diseases. Although illegal to smoke while on HOT,
      there is an increasing incidence of burn injuries in those patients who smoke
      while on HOT. The importance of recognition of the prevalence of this injury, the
      obstacles faced when treating these patients, and understanding the proposed
      algorithmic approach to be taken with patients on HOT, including prescription,
      reassessment, and prevention of burn injury are outlined in this review.
      Retrospective epidemiological data including circumstances, admission, treatment,
      and disposition were collected and reviewed on the patients treated from 1999 to
      2008 with burns secondary to smoking while on HOT. Seventeen patients sustained
      injuries secondary to smoking on HOT over the 9-year period; 9 patients were
      female and 8 were male. All the patients were on HOT for chronic obstructive
      pulmonary disease. Mean patient age was 69.1 +/- 2.5 years and mean TBSA 2.8 +/-
      0.4%; 11.8% (2/17) sustained inhalation injury requiring intubation and 23.5%
      (4/17) required wound debridement and skin grafting. Mean hospital stay was 42.8
      +/- 12.5 days; 10.3 +/- 5.4 days in the burn intensive care unit and 32.5 +/-
      11.0 days in the ward. Before the burn injury, 23.5% (4/17) lived in long-term
      care facilities. On discharge from hospital, 47.1% (8/17) were transferred to
      extended care facilities or other acute care hospitals, and 11.8% (2/17) died
      during their hospitalization. After recovery, there was a 35.3% reduction in
      patients able to return home and/or live independently. A significant number of
      burn injuries secondary to smoking while on HOT was observed. These patients
      differ from standard burn patients because they are older in age, have higher
      rates of inhalation injury, and have much longer lengths of hospitalization,
      despite smaller TBSA injuries. Prevention of this injury would improve the safety
      of the patient and those around them as well as healthcare resource allocation. A
      proactive multidisciplinary algorithmic approach is presented which can be used
      to manage patients on HOT at risk for continued smoking to decrease the incidence
      and the impact of burn injuries in this patient population.

PMID- 21959208
TI  - Presidential address:  looking back in order to look ahead.

PMID- 21959209
TI  - Prognostic factors and visual outcome for fireworks-related burns during spring
      festival in South China.
AB  - The aim of this study was to evaluate the clinical features and the visual
      results of fireworks-related ocular burn injuries and to determine the prognostic
      factors. The authors conducted a prospective observational study of 53 eyes of 46
      consecutive patients with fireworks-related ocular injury who visited Zhongshan
      Ophthalmic Center during the Spring Festival in Southern China. Eyes were graded
      using an ocular trauma classification system, which included age of the patient.
      Patients were followed up for a minimum of 5 months. Best-corrected visual acuity
      at the last follow-up was considered the final visual outcome. Data were analyzed
      with SPSS version 13.0 (SPSS, Inc., Chicago, IL). Results of statistical tests
      were considered statistically significant for P < .05. Almost all patients
      (89.1%) were male with a mean age of 14.3 +/- 8.5 years. There was preponderance
      of young patients, with 63.0% (29) of the patients being younger than 15 years.
      In addition to their ocular injuries, 23 patients (50.0%) also had eyelid and/or
      facial burns. The most common initial anterior segment injuries were open-globe
      injuries (42, 79.3%), conjunctival burns (16, 30.2%), and foreign bodies (18,
      34.0%). Others were traumatic cataract, lens subluxation and dislocation, and
      vitreous hemorrhage. Management after first aid included pars plana vitrectomy
      (9, 17.0%), aspiration of cataract (18, 34.0%), retinal reattachment (8, 15.1%),
      and enucleation. Amniotic membrane grafts were used in 11 patients (20.8%) with
      serious conjunctiva burns and corneal contusions and abrasions who were thought
      to have a good prognosis. Fireworks-related ocular injuries included a variety of
      clinical manifestations. Examinations such as B scan, optical coherence
      tomography, and ultrasound biomicroscopy helped to make a correct diagnosis and
      plan further treatment. Fireworks-related ocular injuries commonly affect young
      male subjects of Southern China. Visual outcomes were frequently poor and
      visually devastating. Laws should be passed to forbid the personal use of
      fireworks in China, and public education on the sale and use of fireworks should
      be increased.

PMID- 21959210
TI  - Burn injuries requiring hospitalization for infants younger than 1 year.
AB  - To investigate burn injuries requiring hospitalization sustained during the first
      year of life, clinical data collected during hospital treatment of infants
      younger than 1 year were reviewed. The principal aim was to chart the etiology
      and mechanism of burn injuries in this group to focus on the necessary preventive
      measures. The authors also review literature focusing especially on children
      younger than 1 year. Patients identified in the electronic database were referred
      to the Hospital for Children and Adolescents, Helsinki University Hospital,
      Helsinki, Finland, from January 2005 to December 2009. Specific inclusion
      criteria yielded a cohort of 20 patient records, which accounted for 3% of the
      692 admissions due to pediatric burn injury during the 5-year study period. The
      male to female ratio was 1:1.5 and the mean age was 6.3 months. Most burns were
      sustained at home during domestic tasks and were most often witnessed. The
      etiology in the majority of the cases was scalding (85%), while contact burns
      accounted for the remaining. The final TBSA ranged from 0.5 to 40% (mean 8.5%).
      In 13 cases (65%), the initial TBSA was overestimated. Overall, it was concluded
      that burn injuries in this age group are most often witnessed and take place
      while the infant is being held at the same time as the hot item. Parental
      education on typical situations in which burn injuries happen in preambulatory
      infants may help reduce the number of burn injuries.

PMID- 21959211
TI  - Practice guidelines for early ambulation of burn survivors after lower extremity
      grafts.
AB  - The objective of this review was to systematically evaluate the available
      clinical evidence for early ambulation of burn survivors after lower extremity
      skin grafting procedures so that practice guidelines could be proposed. It
      provides evidence-based recommendations, specifically for the rehabilitation
      interventions required for early ambulation of burn survivors. These guidelines
      are designed to assist all healthcare providers who are responsible for
      initiating and supporting the ambulation and rehabilitation of burn survivors
      after lower extremity grafting. Summary recommendations were made after the
      literature, retrieved by systematic review, was critically appraised and the
      level of evidence determined according to Oxford Centre for Evidence-Based
      Medicine criteria. A formal consensus exercise was performed to address some of
      the identified gaps in the literature which were believed to be critical building
      blocks of clinical practice.

PMID- 21959212
TI  - In response: tissue expansion and latissimus dorsi transfer for arm thorax
      synechia.

PMID- 21959213
TI  - Volumetric MR-HIFU ablation of uterine fibroids: role of treatment cell size in
      the improvement of energy efficiency.
AB  - PURPOSE: To evaluate the energy efficiency of differently sized volumetric
      ablations in MR-guided high-intensity focused ultrasound (MR-HIFU) treatment of
      uterine fibroids. MATERIALS AND METHODS: This study was approved by the
      institutional review board and informed consent was obtained from all
      participants. Ten symptomatic uterine fibroids (mean diameter 8.9 cm) in 10 women
      (mean age 42.2) were treated by volumetric MR-HIFU ablation under binary feedback
      control. The energy efficiency (mm3/J) of each sonication was calculated as the
      volume of lethal thermal dose (240 equivalent minutes at 43  degrees C) per unit
      acoustic energy applied. Operator-controllable parameters and signal intensity
      ratio of uterine fibroid to skeletal muscle on T2-weighted MR images were tested
      with univariate and multivariate analyses to discern which parameters
      significantly correlated with the ablation energy efficiency. RESULTS: We
      analyzed a total of 236 sonications. The energy efficiency of the ablations was
      0.42+/-0.25 mm3/J (range 0.004-1.18) with energy efficiency improving with the
      treatment cell size (4 mm, 0.06+/-0.06 mm3/J; 8 mm, 0.29+/-0.12 mm3/J; 12 mm,
      0.58+/-0.18 mm3/J; 16 mm, 0.91+/-0.17 mm3/J). Treatment cell size (r=0.814,
      p<0.001), distance of ultrasound propagation (r=-0.151, p=0.020), sonication
      frequency (1.2 or 1.45 MHz; p<0.001), and signal intensity ratio (r=-0.205,
      p=0.002) proved to be significant by univariate analysis, while multivariate
      analysis revealed treatment cell size (B=0.075, p<0.001), US propagation distance
      (B=-6.928, p<0.001), and signal intensity ratio (B=-0.024, p=0.001) to be
      independently significant. CONCLUSION: Energy efficiency in volumetric MR-HIFU
      ablation of uterine fibroids improves with increased treatment cell size,
      independent of other significant contributors such as distance of ultrasound
      propagation or signal intensity of the tumor on T2-weighted MR imaging.

PMID- 21959214
TI  - Screening and follow-up of living kidney donors: a systematic review of clinical
      practice guidelines.
AB  - To minimize the health risks faced by living kidney donors, multiple clinical
      practice guidelines have been developed on the assessment and care of potential
      donors. This study aims to compare the quality, scope, and consistency of these
      guidelines. We searched for guidelines on living kidney donation in electronic
      databases, guideline registries, and relevant Web sites to February 21, 2011.
      Methodological quality was assessed using the Appraisal of Guidelines for
      Research and Education (AGREE) instrument. Textual synthesis was used to compare
      guideline recommendations. Ten guidelines, published from 1996 to 2010, were
      identified. Although generally comprehensive, scope varied considerably and
      mostly appeared to lack methodological rigor. Many recommendations were
      consistent, but important differences were evident, particularly for thresholds
      for comorbidities which precluded donation; obesity/overweight (body mass index,
      30-35 kg/m), diabetes/prediabetes (fasting blood glucose level, 6.1-7.0 mmol/L
      and oral glucose tolerance test, 7.8-11.1 mmol/L), hypertension (130/85 to 140/90
      mm Hg), cardiovascular disease, malignancy, and nephrolithiasis. The importance
      of informed voluntary consent, genuine motivation, support, and psychological
      health were recognized but difficult to implement as specific tools for
      conducting psychosocial assessments were not recommended. Multiple major
      guidelines for living kidney donation have been published recently, resulting in
      unnecessary duplicative efforts. Most do not meet standard processes for
      development, and important recommendations about thresholds for exclusion based
      on comorbidities are contradictory. There is an urgent need for international
      collaboration and coordination to ensure, where possible, that guidelines for
      living donation are consistent, evidence based, and comprehensive to promote best
      outcomes for a precious resource.

PMID- 21959215
TI  - Outcomes of preemptive kidney with or without subsequent pancreas transplant
      compared with preemptive simultaneous pancreas/kidney transplantation.
AB  - BACKGROUND: Prior studies have indicated that type 1 diabetic (T1DM) recipients
      of a simultaneous pancreas-kidney (SPK) transplant have greater short-term
      mortality compared with living donor kidney (LDK) transplantation. Whether this
      association remains and how outcomes compare to deceased donor kidney (DDK)
      transplantation in the preemptive setting are unknown. METHODS: Using data on
      recipients transplanted between 2000 and 2010 from the Organ Procurement and
      Transplantation Network/United Network of Organ Sharing, patient and graft
      survival (calculated from the time of kidney transplant) of pancreas after
      preemptive LDK (PALK, n=389), preemptive LDK not receiving a pancreas transplant
      (LDK/noP, n=289), preemptive DDK (n=112), and preemptive SPK transplantations
      (n=1402) were compared. RESULTS: At 6 years, patient survival was excellent
      (PALK=89.4%, LDK/noP=84.9%, DDK=81.2%, and SPK=91.1%) and not different between
      PALK, LDK/noP, and SPK (P value vs. PALK: LDK/noP=0.08; SPK=0.85) but was lower
      with preemptive DDK versus preemptive PALK (P=0.03). When both LDK groups were
      considered together, there was higher mortality in the first 180 days after
      transplant with preemptive DDK (3.7% vs. 1.1%; P=0.03) and similar mortality with
      preemptive SPK (2.3%; P=0.07). After multivariate adjustment, there was a trend
      toward increased risk of death with preemptive DDK compared with preemptive PALK
      (hazard ratio: 1.91; 95% confidence interval: 0.95-3.84). CONCLUSIONS: Patient
      survival associated with preemptive transplantation among T1DM recipients was
      excellent at 6 years, with the greatest survival favoring PALK, LDK/noP, and SPK
      rather than DDK. In contrast with prior studies reporting greater short-term
      mortality with SPK among the general T1DM population, short-term mortality after
      preemptive transplant is similar between LDK and SPK.

PMID- 21959216
TI  - Antibody removal before ABO-incompatible renal transplantation: how much plasma
      exchange is therapeutic?
AB  - BACKGROUND: ABOi transplantation is an accepted method of expanding the kidney
      donor pool but there is little analysis of the protocols used. We established an
      ABOi programme utilising leukocyte depletion, tacrolimus, TPE and IvIg. There are
      few reports in the literature on the success rates of antibody removal protocols
      or relating to patients in whom antibody removal fails. The purpose of this study
      was to define the likelihood of achieving transplantation depending on ABO
      antibody titers. METHODS: 56 patients entered our ABOi program. Data were
      analysed to determine the likelihood of achieving transplantation, ABO antibody
      titre prior to antibody removal and amount of TPE required to achieve
      transplantation. The median antibody titer was 1:64 (Range 0-1:1024).
      Transplantation proceeded when the ABO titer reached <=1:4. RESULTS: 51/56 (91%)
      patients achieved transplantation after 8.3+/-5 TPE. Five patients with high ABO
      titers were not transplanted despite extensive TPE. The number of TPE required to
      reach an ABO titer of <=1:4 correlates best with pre-treatment IgG titers.
      CONCLUSIONS: This is the first study to demonstrate a cut off titer for entry in
      to the ABO incompatible program using the relationship between ABO titer and
      amount of TPE required to reach transplantation. We now tailor the antibody
      removal protocol prior to transplantation and have introduced a cut-off entry
      titer to the program (<=1:256), because of the unacceptable risk of exposing
      patients with higher titers to long-lasting immunosuppression and costly,
      prolonged, courses of TPE without the guarantee of successful transplantation.
      Patients whose ABO titer exceeds the cut-off are counselled and offered
      alternative routes to transplantation.

PMID- 21959217
TI  - The growth arrest-specific 6 (Gas6) gene polymorphism c.834+7G>A is associated
      with type 2 diabetes.
AB  - AIMS: The plasma protein growth arrest-specific 6 (Gas6) is important to the
      inflammatory process and involved in the development of diabetic renal and
      vascular complications. Recently, Gas6 protein also represents a novel
      independent risk factor of type 2 diabetes. We further investigated the
      association of c.843+7G>A Gas6 polymorphism and type 2 diabetes. METHODS: A total
      of 278 adults, including 96 with normal glucose tolerance (NGT), 82 with impaired
      glucose tolerance (IGT), and 100 with type 2 diabetes were recruited. All
      subjects were genotyped for c.843+7G>A Gas6 polymorphism. RESULTS: Plasma Gas6
      concentrations were significantly lower among patients with type 2 diabetes
      compared to subjects with IGT and NGT. Subjects with Gas6 c.843+7AA genotype had
      higher Gas6 levels and lower glucose values than GG genotype. The AA genotype and
      A allele were less frequent in patients with type 2 diabetes compared with NGT
      subjects. In univariate analysis, the AA genotype was found to be associated with
      a decreased risk for type 2 diabetes. Moreover, the association was even stronger
      after adjustment for established diabetes risk factors. CONCLUSIONS: The Gas6
      c.843+7AA genotype and A allele are less prevalent in type 2 diabetes, which may
      have a protective role for type 2 diabetes.

PMID- 21959218
TI  - Interleukin-10 deficiency impairs bone marrow-derived endothelial progenitor cell
      survival and function in ischemic myocardium.
AB  - RATIONALE: Endothelial progenitor cell (EPC) survival and function in the injured
      myocardium is adversely influenced by hostile microenvironment such as ischemia,
      hypoxia, and inflammatory response, thereby compromising full benefits of EPC
      mediated myocardial repair. OBJECTIVE: We hypothesized that interleukin-10 (IL
      10) modulates EPC biology leading to enhanced survival and function after
      transplantation in the ischemic myocardium. METHODS AND RESULTS: Myocardial
      infarction (MI)-induced mobilization of bone marrow EPC (Sca-1+Flk1+cells) into
      the circulation was significantly impaired in IL-10 knockout (KO) mice. Bone
      marrow transplantation to replace IL-10 KO marrow with wild-type (WT) marrow
      attenuated these effects. Impaired mobilization was associated with lower stromal
      cell-derived factor (SDF)-1 expression levels in the myocardium of KO mice.
      Interestingly, SDF-1 administration reversed mobilization defect in KO mice. In
      vitro, hypoxia-mediated increases in CXCR4 expression and cell survival were
      lower in IL-10-deficient EPCs. Furthermore, SDF-1-induced migration of WT EPCs
      was inhibited by AMD3100, an inhibitor of CXCR4. To further study the effect of
      IL-10 on in vivo EPC survival and engraftment into vascular structures, GFP
      labeled EPC were injected intramyocardially after induction of MI, and the mice
      were treated with either saline or recombinant IL-10. The IL-10-treated group
      showed increased retention of transplanted EPCs in the myocardium and was
      associated with significantly reduced EPC apoptosis after MI. Interestingly,
      increased EPC retention and their association with the vascular structures was
      observed in IL-10-treated mice. Increased EPC survival and angiogenesis in the
      myocardium of IL-10-treated mice corroborated with improved left ventricular
      function, reduced infarct size, and fibrosis in the myocardium. In vitro, IL-10
      induced increase in VEGF expression in WT EPC was abrogated by STAT3 inhibitor,
      suggesting IL-10 signals through STAT3 activation. CONCLUSIONS: Taken together,
      our studies demonstrate that MI-induced EPC mobilization was impaired in IL-10 KO
      mice and that IL-10 increases EPC survival and function possibly through
      activation of STAT3/VEGF signaling cascades, leading to attenuation of MI-induced
      left ventricular dysfunction and remodeling.

PMID- 21959219
TI  - Rip2 deficiency leads to increased atherosclerosis despite decreased
      inflammation.
AB  - RATIONALE: The innate immune system and in particular the pattern-recognition
      receptors Toll-like receptors have recently been linked to atherosclerosis.
      Consequently, inhibition of various signaling molecules downstream of the Toll
      like receptors has been tested as a strategy to prevent progression of
      atherosclerosis. Receptor-interacting protein 2 (Rip2) is a serine/threonine
      kinase that is involved in multiple nuclear factor-kappaB (NFkappaB) activation
      pathways, including Toll-like receptors, and is therefore an interesting
      potential target for pharmaceutical intervention. OBJECTIVE: We hypothesized that
      inhibition of Rip2 would protect against development of atherosclerosis. METHODS
      AND RESULTS: Surprisingly, and contrary to our hypothesis, we found that mice
      transplanted with Rip2(-/-) bone marrow displayed markedly increased
      atherosclerotic lesions despite impaired local and systemic inflammation.
      Moreover, lipid uptake was increased whereas immune signaling was reduced in
      Rip2(-/-) macrophages. Further analysis in Rip2(-/-) macrophages showed that the
      lipid accumulation was scavenger-receptor independent and mediated by Toll-like
      receptor 4 (TLR4)-dependent lipid uptake. CONCLUSIONS: Our data show that lipid
      accumulation and inflammation are dissociated in the vessel wall in mice with
      Rip2(-/-) macrophages. These results for the first time identify Rip2 as a key
      regulator of cellular lipid metabolism and cardiovascular disease.

PMID- 21959220
TI  - Histone deacetylase 3 regulates smooth muscle differentiation in neural crest
      cells and development of the cardiac outflow tract.
AB  - RATIONALE: The development of the cardiac outflow tract (OFT) and great vessels
      is a complex process that involves coordinated regulation of multiple progenitor
      cell populations. Among these populations, neural crest cells make important
      contributions to OFT formation and aortic arch remodeling. Although numerous
      signaling pathways, including Notch, have been implicated in this process, the
      role of epigenetics in OFT development remains largely unexplored. OBJECTIVE:
      Because histone deacetylases (Hdacs) play important roles in the epigenetic
      regulation of mammalian development, we have investigated the function of Hdac3,
      a class I Hdac, during cardiac neural crest development in mouse. METHODS AND
      RESULTS: Using 2 neural crest drivers, Wnt1-Cre and Pax3(Cre), we show that loss
      of Hdac3 in neural crest results in perinatal lethality and cardiovascular
      abnormalities, including interrupted aortic arch type B, aortic arch hypoplasia,
      double-outlet right ventricle, and ventricular septal defect. Affected embryos
      are deficient in aortic arch artery smooth muscle during midgestation, despite
      intact neural crest cell migration and preserved development of other cardiac and
      truncal neural crest derivatives. The Hdac3-dependent block in smooth muscle
      differentiation is cell autonomous and is associated with downregulation of the
      Notch ligand Jagged1, a key driver of smooth muscle differentiation in the aortic
      arch arteries. CONCLUSIONS: These results indicate that Hdac3 plays a critical
      and specific regulatory role in the neural crest-derived smooth muscle lineage
      and in formation of the OFT.

PMID- 21959221
TI  - Clinical long-term outcome after implantation of titanium nitride-oxide coated
      stents compared with paclitaxel- or sirolimus-eluting stents: propensity-score
      matched analysis.
AB  - AIMS: We performed a propensity score matched analysis to explore whether TiNOX
      stents are superior to paclitaxel- (PES) and sirolimus-eluting stents (SES) in
      routine clinical practice. METHODS AND RESULTS: A total of 1,607 patients
      undergoing implantation of SES, PES or TiNOX stents were prospectively entered
      into a stent registry and followed up for three years. Using propensity score
      matching, we compared clinical outcome among 319 pairs of patients treated with
      TiNOX stents or SES and 337 pairs of patients treated with TiNOX stents or PES.
      The primary outcome MACE, a composite of death, myocardial infarction, and target
      vessel revascularisation occurred in 20% of patients with TiNOX stents, 19% of
      patients with SES and 23% of patients with PES at 3-years. The hazard ratio was
      1.00 comparing TiNOX stents with SES (95% CI 0.69-1.45, p=1.00), and 0.95
      comparing TiNOX stents with PES (95% CI 0.66-1.36, p=0.78). CONCLUSION: We did
      not find evidence to suggest superiority of TiNOX stents over SES or PES. In view
      of similar clinical outcomes, but with the reduced duration of dual antiplatelet
      therapy used with the TiNOX stent, we suggest that TiNOX stents may be an
      alternative to drug-eluting stents in patients unsuitable for long-term dual
      antiplatelet therapy.

PMID- 21959222
TI  - Joint inflammation alters gene and protein expression and leads to atrophy in the
      tibialis anterior muscle in rats.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of tibiotarsal joint
      inflammation in rat tibialis anterior muscle through muscle fiber cross-sectional
      area (CSA) and gene expression (atrogin-1, muscle ring finger-1 [MuRF1], myogenic
      differentiation-1 [MyoD], p38 mitogen-activated protein kinase [p38MAPK], nuclear
      factor kappa B-dependent [NFkappaB], tumor necrosis factor-alpha [TNF-alpha]).
      DESIGN: Wistar rats were randomly divided into three periods (2, 7, and 15 days)
      and assigned into four groups within each experimental period: control, sham,
      inflammation, and immobilization. Real-time polymerase chain reaction, Western
      blot, immunofluorescence, and muscle fiber CSA analyses were performed. RESULTS:
      At 2 days, the inflammation group increased atrogin-1, MuRF1, and myostatin and
      reduced MyoD expression. At 7 days, the inflammation group increased atrogin-1,
      MuRF1, NFkappaB, p38MAPK, MyoD, myostatin, and TNF-alpha expression and TNF-alpha
      protein and reduced muscle fiber CSA. At 15 days, gene and protein expression in
      the inflammation group returned to basal levels, and CSA values were similar to
      those in control and sham groups. The immobilization groups have a similar
      pattern in all experimental periods, with increased atrogin-1, MuRF1, NFkappaB,
      and TNF-alpha gene expression and reduced muscle fiber CSA. The sham group had
      increased myostatin and atrogin-1 expression at 2 days and increased MyoD and
      myostatin expression at 7 days. CONCLUSIONS: Joint inflammation stimulated the
      expression of muscle factors related to atrophy, growth, differentiation, and
      mass regulation followed by muscle atrophy.

PMID- 21959223
TI  - Development of the RTI item bank on risk of bias and precision of observational
      studies.
AB  - OBJECTIVE: To create a practical and validated item bank for evaluating the risk
      of bias and precision of observational studies of interventions or exposures
      included in systematic evidence reviews. STUDY DESIGN AND SETTING: The item bank,
      developed at RTI International, was created based on 1,492 questions included in
      earlier instruments, organized by the quality domains identified by Deeks et al.
      Items were eliminated and refined through face validity, cognitive, content
      validity, and interrater reliability testing. RESULTS: The resulting item bank
      consisting of 29 questions for evaluating the risk of bias and precision of
      observational studies of interventions or exposures (1) captures all of the
      domains critical for evaluating this type of research, (2) is comprehensive and
      can be easily lifted "off the shelf" by different researchers, (3) can be adapted
      to different topic areas and study types (e.g., cohort, case-control, cross
      sectional, and case series studies), and (4) provides sufficient instruction to
      apply the tool to varied topics. CONCLUSION: One bank of items, with specific
      instructions for focusing abstractor evaluations, can be created to judge the
      risk of bias and precision of the variety of observational studies that may be
      used in systematic and comparative effectiveness reviews.

PMID- 21959224
TI  - Near-infrared autofluorescence spectroscopy for in vivo identification of
      hyperplastic and adenomatous polyps in the colon.
AB  - This study reports the implementation of an endoscope-based near-infrared (NIR)
      autofluorescence (AF) spectroscopy technique for in vivo differentiation of
      normal, hyperplastic and adenomatous colonic polyps during clinical colonoscopic
      examination. A total of 198 in vivo NIR AF spectra in the range of 810-1050 nm
      were acquired from colonic tissues (normal (n=116); hyperplastic (n=48); and
      adenomatous polyps (n=34)) of 96 patients undergoing colonoscopic screening.
      Significant differences (p<0.001, one-way analysis of variance (ANOVA)) in in
      vivo NIR AF intensity among normal, hyperplastic, and adenomatous polyps are
      observed. Multivariate statistical techniques, including principal components
      analysis (PCA) and linear discriminate analysis (LDA) together with the leave-one
      tissue site-out, cross-validation, were used to develop diagnostic algorithms for
      distinguishing adenomatous polyps from normal and hyperplastic colonic polyps
      based on NIR AF spectral features. The PCA-LDA modeling on in vivo colonic NIR AF
      dataset yields diagnostic sensitivities of 83.6%, 77.1%, and 88.2%; and
      specificities of 96.3%, 88.0%, and 92.1%, respectively, for classification of
      normal, hyperplastic and adenomatous colonic polyps. This work suggests that NIR
      AF spectroscopy associated with PCA-LDA algorithms has potential for in vivo
      diagnosis and detection of colonic precancer at colonoscopy.

PMID- 21959225
TI  - One-step "green" preparation of graphene nanosheets and carbon nanospheres
      mixture by electrolyzing graphite rob and its application for glucose biosensing.
AB  - The graphene nanosheets and carbon nanospheres mixture (GNS-CNS) was prepared by
      electrolyzing graphite rob in KNO(3) solution under constant current, which was
      characterized by TEM, AFM, SEM, FT-IR, XRD, XPS, TGA and UV-vis. The nano-mixture
      can keep stable in water for more than one month. Based on this kind of mixture
      material, a novel electrochemical biosensing platform for glucose determination
      was developed. Cyclic voltammetry of glucose oxidase (GOD) immobilized on GNS
      CNS/GCE exhibited a pair of well-defined quasi-reversible redox peaks at -0.488 V
      (E(pa)) and -0.509 V (E(pc)) by direct electron transfer between the protein and
      the electrode. The charge-transfer coefficient (alpha) was 0.51, the electron
      transfer rate constant was 2.64 s(-1) and the surface coverage of HRP was
      3.18*10(-10) mol cm(-2). The immobilized GOD could retain its bioactivity and
      catalyze the reduction of dissolved oxygen. The glucose biosensor has a linear
      range from 0.4 to 20 mM with detection limit of 0.1 mM. Moreover, the biosensor
      exhibits acceptable reproducibility and storage stability. The fabricated
      biosensor was further used to determine glucose in human plasma sample with the
      recoveries from 96.83% to 105.52%. Therefore, GOD/GNS-CNS/GCE could be
      promisingly applied to determine blood sugar concentration in the practical
      clinical analysis.

PMID- 21959226
TI  - Multifunctional carbon nanotubes for direct electrochemistry of glucose oxidase
      and glucose bioassay.
AB  - Polydopamine (Pdop) has recently been shown to adsorb to a wide variety of
      surfaces and serves as an adhesion layer to immobilize biological molecules. In
      this work, the multifunctional carbon nanotube (CNT) composites were prepared
      though the oxidation of dopamine at room temperature and subsequent electroless
      silver deposition by mildly stirring. The stable immobilization and direct
      electron transfer of glucose oxidase were achieved on the composite film modified
      glassy carbon electrode. The resulting electrode gave a well-defined redox peaks
      with a formal potential of about -482 mV (vs. SCE) in pH 7.0 buffer. The electron
      transfer rate constant was estimated to be 3.6 s(-1), due to the combined
      contribution of Pdop, CNTs and Ag nanoparticles with the help of Nafion.
      Furthermore, the method for detecting of glucose was proposed based on the
      decrease of oxygen caused by the enzyme-catalyzed reaction between glucose
      oxidase (GOD) and glucose. The linear response to glucose ranging from 50.0 MUM
      to 1.1 mM (R(2)=0.9958), with a calculated detection limit of 17.0 MUM at a
      signal-to-noise ratio of 3. The low calculated apparent Michaelis-Menten constant
      (K(M)(app)) was 5.46 mM, implying the high enzymatic activity and affinity of
      immobilized GOD for glucose. It can reasonably be expected that this observation
      might hold true for other noble metal nanostructure-electroactive protein
      systems, providing a promising platform for the development of biosensors and
      biofuel cells.

PMID- 21959227
TI  - Electrochemical impedance spectroscopy to characterize inflammatory
      atherosclerotic plaques.
AB  - Despite advances in diagnosis and therapy, atherosclerotic cardiovascular disease
      remains the leading cause of morbidity and mortality in the Western world.
      Predicting metabolically active atherosclerotic lesions has remained an unmet
      clinical need. We hereby developed an electrochemical strategy to characterize
      the inflammatory states of high-risk atherosclerotic plaques. Using the
      concentric bipolar microelectrodes, we sought to demonstrate distinct
      Electrochemical Impedance Spectroscopic (EIS) measurements for unstable
      atherosclerotic plaques that harbored active lipids and inflammatory cells. Using
      equivalent circuits to simulate vessel impedance at the electrode-endoluminal
      tissue interface, we demonstrated specific electric elements to model working and
      counter electrode interfaces as well as the tissue impedance. Using explants of
      human coronary, carotid, and femoral arteries at various Stary stages of
      atherosclerotic lesions (n=15), we performed endoluminal EIS measurements (n=147)
      and validated with histology and immunohistochemistry. We computed the vascular
      tissue resistance using the equivalent circuit model and normalized the
      resistance to the lesion-free regions. Tissue resistance was significantly
      elevated in the oxLDL-rich thin-cap atheromas (1.57+/-0.40, n=14, p<0.001) and
      fatty streaks (1.36+/-0.28, n=33, p<0.001) as compared with lesion-free region
      (1.00+/-0.18, n=82) or oxLDL-absent fibrous atheromas (0.86+/-0.30, n=12). Tissue
      resistance was also elevated in the calcified core of fibrous atheroma (2.37+/
      0.60, n=6, p<0.001). Despite presence of fibrous structures, tissue resistance
      between ox-LDL-absent fibroatheroma and the lesion-free regions was statistically
      insignificant (0.86+/-0.30, n=12, p>0.05). Hence, we demonstrate that the
      application of EIS strategy was sensitive to detect fibrous cap oxLDL-rich
      lesions and specific to distinguish oxLDL-absent fibroatheroma.

PMID- 21959228
TI  - Using method triangulation to validate a new instrument (CPWQ-com) assessing
      cancer patients' satisfaction with communication.
AB  - PURPOSE: Patients' perceptions of care including the communication with health
      care staff is recognized as an important aspect of the quality of cancer care.
      Using mixed methods, we developed and validated a short instrument assessing this
      communication. METHODS: Based on focus group interviews with 77 informants, an 8
      item instrument was developed. This short instrument aimed at assessing overall
      aspects of the communication between cancer patients and health care staff. The
      items were validated first through cognitive interviews with patient-observer
      agreement with 52 cancer patients who completed the questions and then
      participated in tape-recorded open-ended interviews. Observer ratings of the
      interviews were compared with the patients' written responses collected before
      interviews and kappa values were calculated. The comprehensibility of each item
      was subsequently elaborated in traditional cognitive interviews with 17 cancer
      patients. Finally, psychometric analyses took place with data from 1490 cancer
      patients. RESULTS: The weighted kappas concerning patient-observer agreement
      ranged 0.31-0.88. Disagreements mainly consisted of the observer choosing the
      response category indicating the highest level of satisfaction whereas the
      patients had chosen the second highest level. Cognitive interviews showed that
      the questions were generally interpreted as intended. One item was excluded due
      to low validity. A sum scale of the remaining seven items had high reliability
      (Cronbach's alpha 0.89). CONCLUSIONS: Seven items performed well. They proved to
      be valid measures of satisfaction with communication with the health care staff
      and constitute a sum scale with high reliability. The cognitive interviews
      provided valuable insight into the patients' perception of communication.

PMID- 21959229
TI  - Activation of apoptosis by ethyl acetate fraction of ethanol extract of Dianthus
      superbus in HepG2 cell line.
AB  - Dianthus superbus L. is commonly used as a traditional Chinese medicine. We
      recently showed that ethyl acetate fraction (EE-DS) from ethanol extract of D.
      superbus exhibited the strongest antioxidant and cytotoxic activities. In this
      study, we examined apoptosis of HepG2 cells induced by EE-DS, and the mechanism
      underlying apoptosis was also investigated. Treatment of HepG2 cells with EE-DS
      (20-80 MUg/ml) for 48 h led to a significant dose-dependent increase in the
      percentage of cells in sub-G1 phase by analysis of the content of DNA in cells,
      and a large number of apoptotic bodies containing nuclear fragments were observed
      in cells treated with 80 MUg/ml of EE-DS for 24 h by using Hoechst 33258
      staining. These data show that EE-DS can induce apoptosis of HepG2 cells.
      Immunoblot analysis showed that EE-DS significantly suppressed the expressions of
      Bcl-2 and NF-kappaB. Treatment of cells with EE-DS (80 MUg/ml) for 48 h resulted
      in significant increase of cytochrome c in the cytosol, which indicated
      cytochrome c release from mitochondria. Activation of caspase-9 and -3 were also
      determined when the cells treated with EE-DS. The results suggest that apoptosis
      of HepG2 cells induced by EE-DS could be through the mitochondrial intrinsic
      pathway. High performance liquid chromatography (HPLC) data showed that the
      composition of EE-DS is complicated. Further studies are needed to find the
      effective constituents of EE-DS.

PMID- 21959230
TI  - Expected long-term survival of older patients diagnosed with non-Hodgkin lymphoma
      in 2008-2012.
AB  - BACKGROUND: New therapeutic options have led to substantial increases in survival
      expectations of patients with non-Hodgkin lymphoma (NHL) in recent years. In
      contrast to many malignancies, survival in older patients has improved in NHL at
      a rate similar to that in younger patients. In the past, the impact of
      innovations on long-term survival of NHL patients on the population level has
      been disclosed only with substantial delay. METHODS: We employ a novel model
      based projection method to estimate survival expectations of NHL patients age 60+
      diagnosed in 2008-2012. Preliminary empirical evaluation of the method using
      historical data indicates excellent performance in projection of age specific and
      overall 5- and 10-year relative survival. RESULTS: Overall 5- and 10-year
      survival projections for 2008-2012 were 67.5% and 56.9%, respectively, 8.2
      percentage units (% units) and 15.2% units, respectively, higher than the most
      recent survival estimates available from traditional cohort analysis. Projected
      survival decreased with age, ranging from 79.1% for patients age 60-64 to 54.3%
      for patients age 80+. Projected survival estimates for diffuse large B-cell
      lymphoma and follicular lymphoma were 59% and 84.9%, respectively. Survival
      estimates by model-based projection were substantially higher than available
      cohort estimates for all age groups including 80+, each specific morphology
      examined, nodal and extranodal disease, and both genders. CONCLUSIONS: Patients
      over 60 diagnosed with NHL in 2008-2012 have much higher long-term survival
      expectations than suggested by previously available survival statistics.

PMID- 21959231
TI  - Synthesis and anticandidal activity of new triazolothiadiazine derivatives.
AB  - New triazolothiadiazine derivatives were synthesized via the ring closure
      reaction of 4-amino-5-substituted-2,4-dihydro-3H-1,2,4-triazol-3-thiones with
      phenacyl bromides. The compounds were tested in vitro against various Candida
      species and compared with ketoconazole. Among these compounds, the compound
      bearing cyclohexyl moiety and p-chlorophenyl substituent on triazolothiadiazine
      ring (2i) was found to be the most potent derivative against Candida albicans
      (ATCC 90028). It is clear that there is a positive correlation between
      anticandidal activity and two functional moieties, namely cycloaliphatic group
      and p-chlorophenyl substituent on triazolothiadiazine ring. The compounds were
      also investigated for their cytotoxic effects using MTT assay. Compound 2a
      exhibited the highest cytotoxic activity, whereas compound 2f possessed the
      lowest cytotoxic activity against NIH/3T3 cells.

PMID- 21959232
TI  - Synthesis and antitumor activity of ring A modified glycyrrhetinic acid
      derivatives.
AB  - Triterpenoic acids show many pharmacological effects, among them an
      antiinflammatory or an antitumor activity. One of these, glycyrrhetinic acid (1)
      is of interest because of its antitumor profile. Glycyrrhetinic acid is not only
      cytotoxic but also triggers apoptosis in various human tumor cell lines. To
      improve the cytotoxicity of parent 1 we set out to synthesize new derivatives of
      it--differing in structure and lipophilicity. These compounds were tested in a
      sulforhodamine B assay for cytotoxicity, and screened for their ability to induce
      apoptosis using an acridine orange/ethidium bromide assay and trypan blue
      staining. The most active compound, 34, a benzyl glycyrrhetinate holding an extra
      3-N-(3-aminopropyl)glycyl substituent showed IC(50) between 1.96 and 5.14 MUm for
      five human cancer cell lines and triggers apoptosis in 80% of the cells.

PMID- 21959233
TI  - Global urinary metabolic profiling procedures using gas chromatography-mass
      spectrometry.
AB  - The role of urinary metabolic profiling in systems biology research is expanding.
      This is because of the use of this technology for clinical diagnostic and
      mechanistic studies and for the development of new personalized health care and
      molecular epidemiology (population) studies. The methodologies commonly used for
      metabolic profiling are NMR spectroscopy, liquid chromatography mass spectrometry
      (LC/MS) and gas chromatography-mass spectrometry (GC/MS). In this protocol, we
      describe urine collection and storage, GC/MS and data preprocessing methods,
      chemometric data analysis and urinary marker metabolite identification. Results
      obtained using GC/MS are complementary to NMR and LC/MS. Sample preparation for
      GC/MS analysis involves the depletion of urea via treatment with urease, protein
      precipitation with methanol, and trimethylsilyl derivatization. The protocol
      described here facilitates the metabolic profiling of ~400-600 metabolites in 120
      urine samples per week.

PMID- 21959234
TI  - Setup and use of a two-laser multiphoton microscope for multichannel intravital
      fluorescence imaging.
AB  - Characterizing biological mechanisms dependent upon the interaction of many cell
      types in vivo requires both multiphoton microscope systems capable of expanding
      the number and types of fluorophores that can be imaged simultaneously while
      removing the wavelength and tunability restrictions of existing systems, and
      enhanced software for extracting critical cellular parameters from voluminous 4D
      data sets. We present a procedure for constructing a two-laser multiphoton
      microscope that extends the wavelength range of excitation light, expands the
      number of simultaneously usable fluorophores and markedly increases signal to
      noise via 'over-clocking' of detection. We also utilize a custom-written software
      plug-in that simplifies the quantitative tracking and analysis of 4D intravital
      image data. We begin by describing the optics, hardware, electronics and software
      required, and finally the use of the plug-in for analysis. We demonstrate the use
      of the setup and plug-in by presenting data collected via intravital imaging of a
      mouse model of breast cancer. The procedure may be completed in ~24 h.

PMID- 21959235
TI  - Sleeping Beauty transposon mutagenesis in rat spermatogonial stem cells.
AB  - We describe an experimental approach for generating mutant alleles in rat
      spermatogonial stem cells (SSCs) using Sleeping Beauty (SB) transposon-mediated
      insertional mutagenesis. The protocol is based on mobilization of mutagenic gene
      trap transposons from transfected plasmid vectors into the genomes of cultured
      stem cells. Cells with transposon insertions in expressed genes are selected on
      the basis of activation of an antibiotic-resistance gene encoded by the
      transposon. These gene-trap clones are transplanted into the testes of recipient
      males (either as monoclonal or polyclonal libraries); crossing of these founders
      with wild-type females allows the insertions to be passed to F(1) progeny. This
      simple, economic and user-friendly methodological pipeline enables screens for
      functional gene annotation in the rat, with applicability in other vertebrate
      models where germ line-competent stem cells have been established. The complete
      protocol from transfection of SSCs to the genotyping of heterozygous F(1)
      offspring that harbor genomic SB gene-trap insertions takes 5-6 months.

PMID- 21959236
TI  - 3D maps of RNA interhelical junctions.
AB  - More than 50% of RNA secondary structure is estimated to be A-form helices, which
      are linked together by various junctions. Here we describe a protocol for
      computing three interhelical Euler angles describing the relative orientation of
      helices across RNA junctions. 5' and 3' helices, H1 and H2, respectively, are
      assigned based on the junction topology. A reference canonical helix is
      constructed using an appropriate molecular builder software consisting of two
      continuous idealized A-form helices (iH1 and iH2) with helix axis oriented along
      the molecular Z-direction running toward the positive direction from iH1 to iH2.
      The phosphate groups and the carbon and oxygen atoms of the sugars are used to
      superimpose helix H1 of a target interhelical junction onto the corresponding iH1
      of the reference helix. A copy of iH2 is then superimposed onto the resulting H2
      helix to generate iH2'. A rotation matrix R is computed, which rotates iH2' into
      iH2 and expresses the rotation parameters in terms of three Euler angles
      alpha(h), beta(h) and gamma(h). The angles are processed to resolve a twofold
      degeneracy and to select an overall rotation around the axis of the reference
      helix. The three interhelical Euler angles define clockwise rotations around the
      5' (-gamma(h)) and 3' (alpha(h)) helices and an interhelical bend angle
      (beta(h)). The angles can be depicted graphically to provide a 'Ramachandran'
      type view of RNA global structure that can be used to identify unusual
      conformations as well as to understand variations due to changes in sequence,
      junction topology and other parameters.

PMID- 21959237
TI  - Synthesis of functionalized amphiphilic polymers for coating quantum dots.
AB  - Quantum dots (QDs) need to be attached to other chemical species if they are to
      be used as biomarkers, therapeutic agents or sensors. These materials also need
      to disperse well in water and have well-defined functional groups on their
      surfaces. QDs are most often synthesized in the presence of ligands such as
      trioctylphosphine oxide, which render the nanoparticle surfaces hydrophobic. We
      present a complete protocol for the synthesis and water solubilization of
      hydrophobic CdSe/ZnS QDs using designer amphiphilic polymeric coatings. The
      method is based on functionalization of an anhydride polymer backbone with
      nucleophilic agents. Small functional groups, bulky cyclic compounds and
      polymeric chains can be integrated into the coating prior to solubilization. We
      describe the preparation of acetylene- and azide-functionalized QDs for 'click'
      chemistry. The method is universal and applicable to any type of nanoparticle
      stabilized with hydrophobic ligands able to interact with the alkyl chains in the
      coating in water.

PMID- 21959238
TI  - Quantifying spatial correlations of fluorescent markers using enhanced background
      reduction with protein proximity index and correlation coefficient estimations.
AB  - Interactions of proteins are examined by detecting their overlap using
      fluorescent markers. The observed overlap is then quantified to serve as a
      measure of spatial correlation. A major drawback of this approach is that it can
      produce false values because of the properties of the image background. To remedy
      this, we provide a protocol to reduce the contribution of image background and
      then apply a protein proximity index (PPI) and correlation coefficient to
      estimate colocalization. Background heterogeneity is reduced by the median
      filtering procedure, comprising two steps, to reduce random noise and background,
      respectively. Alternatively, background can be reduced by advanced thresholding.
      PPI provides separate values for each channel to characterize the contribution of
      each protein, whereas correlation coefficient determines the overall
      colocalization. The protocol is demonstrated using computer-simulated and real
      biological images. It minimizes human bias and can be universally applied to
      various cell types in which there is a need to understand protein-protein
      interactions. Background reductions require 3-5 min per image. Quantifications
      take <1 min. The entire procedure takes approximately 15-30 min.

PMID- 21959239
TI  - Primary culture of chick, mouse or human neural crest cells.
AB  - A highly enriched population of neural crest cells (NCCs) from amniote embryos,
      such as from chicks, mice and humans, is desirable for experiments in fate
      determination. NCCs are also useful for testing the functional effects of
      molecular changes underlying numerous human diseases of neural crest derivatives
      and for investigating their potential for therapeutic compensation. This protocol
      details embryonic microdissection followed by neural tube explantation.
      Conditions favoring NCC expansion and the maintenance of their stem cell-like
      properties are described. Although neural crest-like cells can be derived from a
      number of sites in the mature organism, full potential is best ensured by their
      purification from their source tissue at the outset of migration. Going from
      embryo to established cell line takes 4 d; the first is the most labor-intensive
      day, but minimal intervention is required thereafter.

PMID- 21959240
TI  - Identifying and quantifying proteolytic events and the natural N terminome by
      terminal amine isotopic labeling of substrates.
AB  - Analysis of the sequence and nature of protein N termini has many applications.
      Defining the termini of proteins for proteome annotation in the Human Proteome
      Project is of increasing importance. Terminomics analysis of protease cleavage
      sites in degradomics for substrate discovery is a key new application. Here we
      describe the step-by-step procedures for performing terminal amine isotopic
      labeling of substrates (TAILS), a 2- to 3-d (depending on method of labeling)
      high-throughput method to identify and distinguish protease-generated neo-N
      termini from mature protein N termini with all natural modifications with high
      confidence. TAILS uses negative selection to enrich for all N-terminal peptides
      and uses primary amine labeling-based quantification as the discriminating
      factor. Labeling is versatile and suited to many applications, including
      biochemical and cell culture analyses in vitro; in vivo analyses using tissue
      samples from animal and human sources can also be readily performed. At the
      protein level, N-terminal and lysine amines are blocked by dimethylation
      (formaldehyde/sodium cyanoborohydride) and isotopically labeled by incorporating
      heavy and light dimethylation reagents or stable isotope labeling with amino
      acids in cell culture labels. Alternatively, easy multiplex sample analysis can
      be achieved using amine blocking and labeling with isobaric tags for relative and
      absolute quantification, also known as iTRAQ. After tryptic digestion, N-terminal
      peptide separation is achieved using a high-molecular-weight dendritic
      polyglycerol aldehyde polymer that binds internal tryptic and C-terminal peptides
      that now have N-terminal alpha amines. The unbound naturally blocked
      (acetylation, cyclization, methylation and so on) or labeled mature N-terminal
      and neo-N-terminal peptides are recovered by ultrafiltration and analyzed by
      tandem mass spectrometry (MS/MS). Hierarchical substrate winnowing discriminates
      substrates from the background proteolysis products and non-cleaved proteins by
      peptide isotope quantification and bioinformatics search criteria.

PMID- 21959242
TI  - Using the Drosophila melanogaster D17-c3 cell culture system to study cell
      motility.
AB  - Cultured Drosophila melanogaster S2 and S2R+ cell lines have become important
      tools for uncovering fundamental aspects of cell biology as well as for gene
      discovery. Despite their utility, these cell lines are nonmotile and cannot build
      polarized structures or cell-cell contacts. Here we outline a previously
      isolated, but uncharacterized, Drosophila cell line named Dm-D17-c3 (or D17).
      These cells spread and migrate in culture, form cell-cell junctions and are
      susceptible to RNA interference (RNAi). Using this protocol, we describe how
      investigators, upon receiving cells from the Bloomington stock center, can
      culture cells and prepare the necessary reagents to plate and image migrating D17
      cells; they can then be used to examine intracellular dynamics or observe loss-of
      function RNAi phenotypes using an in vitro scratch or wound healing assay. From
      first thawing frozen ampules of D17 cells, investigators can expect to begin
      assaying RNAi phenotypes in D17 cells within roughly 2-3 weeks.

PMID- 21959241
TI  - Materials fabrication from Bombyx mori silk fibroin.
AB  - Silk fibroin, derived from Bombyx mori cocoons, is a widely used and studied
      protein polymer for biomaterial applications. Silk fibroin has remarkable
      mechanical properties when formed into different materials, demonstrates
      biocompatibility, has controllable degradation rates from hours to years and can
      be chemically modified to alter surface properties or to immobilize growth
      factors. A variety of aqueous or organic solvent-processing methods can be used
      to generate silk biomaterials for a range of applications. In this protocol, we
      include methods to extract silk from B. mori cocoons to fabricate hydrogels,
      tubes, sponges, composites, fibers, microspheres and thin films. These materials
      can be used directly as biomaterials for implants, as scaffolding in tissue
      engineering and in vitro disease models, as well as for drug delivery.

PMID- 21959243
TI  - Cell analysis using a multiple internal reflection photonic lab-on-a-chip.
AB  - Here we present a protocol for analyzing cell cultures using a photonic lab-on-a
      chip (PhLoC). By using a broadband light source and a spectrometer, the spectrum
      of a given cell culture with an arbitrary population is acquired. The PhLoC can
      work in three different regimes: light scattering (using label-free cells), light
      scattering plus absorption (using stained cells) and, by subtraction of the two
      former regimes, absorption (without the scattering band). The acquisition time of
      the PhLoC is ~30 ms. Hence, it can be used for rapid cell counting, dead/live
      ratio estimation or multiparametric measurements through the use of different
      dyes. The PhLoC, including microlenses, micromirrors and microfluidics, is simply
      fabricated in a single-mask process (by soft lithographic methods) using low-cost
      materials. Because of its low cost it can easily be implemented for point-of-care
      applications. From raw substrates to final results, this protocol can be
      completed in 29 h.

PMID- 21959244
TI  - Whole-genome chromatin profiling from limited numbers of cells using nano-ChIP
      seq.
AB  - Chromatin immunoprecipitation (ChIP) combined with high-throughput sequencing
      (ChIP-seq) has become the gold standard for whole-genome mapping of protein-DNA
      interactions. However, conventional ChIP protocols necessitate the use of large
      numbers of cells, and library preparation steps associated with current high
      throughput sequencing platforms require substantial amounts of DNA; both of these
      factors preclude the application of ChIP-seq technology to many biologically
      important but rare cell types. Here we describe a nano-ChIP-seq protocol that
      combines a high-sensitivity small-scale ChIP assay and a tailored procedure for
      generating high-throughput sequencing libraries from scarce amounts of ChIP DNA.
      In terms of the numbers of cells required, the method provides two to three
      orders of magnitude of improvement over the conventional ChIP-seq method and the
      entire procedure can be completed within 4 d.

PMID- 21959245
TI  - A rating scale for housing-based health hazards.
AB  - OBJECTIVES: This study investigated the validity and responsiveness of a rating
      scale designed to assess the housing-based hazards and their relationships to
      burden of disease symptoms in the building occupants. STUDY DESIGN: A population
      based cross-sectional survey. METHODS: Random-digit dialing with computer
      assisted phone interviews was conducted to obtain information from 642 households
      in the City of Saginaw, Michigan about 71 housing-based hazards, symptoms of 43
      diseases often associated with environmental exposures and demographic
      characteristics. The housing-based hazard index (HHI) was calculated from scores
      of hazards across the following eight dimensions: structural scale (18 items);
      moisture/mold scale (8 items), electrical scale (7 items), ventilation and
      combustion appliances scale (6 items); pest scale (6 items); pets scale (4
      items), fire scale (6 items) and lifestyle-associated factors scale (12 items).
      Each item was assigned a relative score based on the likelihood that the housing
      occupants would be exposed to the hazard, the potential for serious health
      impacts, and the reported strength of its association with childhood lead
      poisoning and respiratory diseases. The psychometric properties of HHI and
      individual domains (scales) were assessed along with the associations between
      these indicators and the inventory of disease symptoms. RESULTS: The reliability
      of HHI was demonstrated by assessments of its dimensionality and internal
      consistency. Analysis of the predictive validity and responsiveness indicates
      that HHI and scores for most of the individual scales can discriminate between
      households in relation to the burden of reported disease symptoms. CONCLUSIONS:
      The HHI represents a valid, reasonably reliable, and parsimonious measure of
      hazards that are congruent with the burden of symptoms generally associated with
      housing-related diseases.

PMID- 21959246
TI  - Observations of nitrogen and phosphorus biogeochemistry in a surface flow
      constructed wetland.
AB  - Free surface water constructed wetlands (CWs) provide a buffer between domestic
      wastewater treatment plants and natural waterways. Understanding the
      biogeochemical processes in CWs is crucial to improve their performance. In this
      study we measured a range of water and sediment parameters, and biogeochemical
      processes, in an effort to describe the processing of nutrients within two
      wetland cells in series. As a whole the studied CW effectively absorbed both
      nitrogen (N) and phosphorus (P) emanating from the waste treatment plant. However
      the two individual cells showed marked differences related to the availability of
      oxygen within the water column and the sediments. In one cell we speculated that
      the prevalence of surface plant species reduced its ability to function as a net
      nutrient sink. Here we observed a build-up of sediment organic matter, sediment
      anoxia, a decoupling of nitrification-denitrification, and a flux of N and P out
      of the sediments to the overlying water. The availability of DO in the surface
      sediments of the second studied cell led to improved coupling between
      nitrification-denitrification and a net uptake of both NH4+ and PO4(3-). We
      hypothesise that the dominance of deeply rooted macrophytes in the second cell
      was responsible for the improved sediment quality.

PMID- 21959247
TI  - Determination of 210Po in various foodstuffs and its annual effective dose to
      inhabitants of Qena City, Egypt.
AB  - The concentration of 210Po was determined in different foodstuffs of plant origin
      purchased from markets in Qena City, Upper Egypt. Measurement of 210Po has been
      carried out using alpha spectrometry technique in different food categories such
      as vegetables, fruits, cereals beverages and herbs. The general range of 210Po
      activity levels ranged widely from <0.010-18.6+/-0.910 mBq g(-1), with minimum
      being in cereal samples and maximum being in beverage samples. Tea samples
      recorded highest activity concentrations of 210Po with lowest value of 10+/-0.54
      mBq g(-1) for Crown tea and highest value of 18.6+/-0.910 mBq g(-1) for El maabad
      tea. The daily intake of 210Po from food consumption reveals that vegetables are
      the biggest contributors, while beverages are the lowest. The effective ingestion
      dose has been estimated for Qena City residents and it was found in the range
      0.008-38.3 MUSv y(-1).

PMID- 21959248
TI  - One century of arsenic exposure in Latin America: a review of history and
      occurrence from 14 countries.
AB  - The global impact on public health of elevated arsenic (As) in water supplies is
      highlighted by an increasing number of countries worldwide reporting high As
      concentrations in drinking water. In Latin America, the problem of As
      contamination in water is known in 14 out of 20 countries: Argentina, Bolivia,
      Brazil, Chile, Colombia, Cuba, Ecuador, El Salvador, Guatemala, Honduras, Mexico,
      Nicaragua, Peru and Uruguay. Considering the 10 MUg/L limit for As in drinking
      water established by international and several national agencies, the number of
      exposed people is estimated to be about 14 million. Health effects of As exposure
      were identified for the first time already in the 1910s in Bellville (Cordoba
      province, Argentina). Nevertheless, contamination of As in waters has been
      detected in 10 Latin American countries only within the last 10 to 15 years.
      Arsenic is mobilized predominantly from young volcanic rocks and their weathering
      products. In alluvial aquifers, which are water sources frequently used for water
      supply, desorption of As from metal oxyhydroxides at high pH (>8) is the
      predominant mobility control; redox conditions are moderate reducing to oxidizing
      and As(V) is the predominant species. In the Andes, the Middle American
      cordillera and the Transmexican Volcanic Belt, oxidation of sulfide minerals is
      the primary As mobilization process. Rivers that originate in the Andean
      mountains, transport As to more densely populated areas in the lowlands (e.g.
      Rimac river in Peru, Pilcomayo river in Bolivia/Argentina/Paraguay). In many
      parts of Latin America, As often occurs together with F and B; in the Chaco
      Pampean plain As is found additionally with V, Mo and U whereas in areas with
      sulfide ore deposits As often occurs together with heavy metals. These co
      occurrences and the anthropogenic activities in mining areas that enhance the
      mobilization of As and other pollutants make more dramatic the environmental
      problem.

PMID- 21959249
TI  - An elutriation device to measure particle settling velocity in urban runoff.
AB  - Urban runoff is primarily treated by settling particles. One important parameter
      in the design of these settling basins is particle settling velocity. Yet, this
      parameter is rarely measured. A modified elutriation device is developed to
      measure particle settling velocity distribution for use in stormwater runoff
      treatment design and performance evaluation. The elutriation device has distinct
      advantages over settling column measurement, including (1) less time requirement
      to make measurements, and (2) flexibility to operate at various flow rates to
      cover wide ranges of particle settling velocity. Major modifications of the
      existing elutriation devices include using a variable speed pump, changing the
      glass column to plastic, and adding screens at the flow inlet for more uniform
      velocity distribution while making the column shorter. The results of the
      experiments showed that the particles retained in each column of the modified
      elutriation device could be predicted by assuming a fully-developed, laminar
      velocity profile across the cross-section of each column. Operation of the device
      under two flow rates and multiple columns increased the range of settling
      velocities measured. The information presented in this paper may be used to
      develop standard protocols for the evaluation of particle settling velocity in
      stormwater.

PMID- 21959250
TI  - Damage-specific DNA binding protein 1 (DDB1): a protein with a wide range of
      functions.
AB  - Damage-specific DNA binding protein 1 (DDB1) is a multifunctional protein that
      was first isolated as a subunit of a heterodimeric complex that recognises the UV
      induced DNA lesions in the nucleotide excision repair pathway. DDB1 and DDB2 form
      a complex that promotes the global genome repair (GG-NER), whereas DDB1 and
      Cockayne syndrome group A protein (CSA) form a complex that contributes to the
      transcription-coupled repair (TC-NER) pathway. DDB1 is also a component of an
      ubiquitin-E3 ligase complex and functions as substrate or adapter protein between
      Cullin 4A (Cul4A) and CUL4-associated factors (DCAFs) to target substrates for
      ubiquitination. CUL4-DDB1 E3-ligase complex regulates the selective proteolysis
      of key proteins in DNA repair, replication and transcription. In addition, DDB1
      plays a role in transcriptional regulation of UV-induced genes. It is conceivable
      that DDB1 acts as a sensor of damage to maintain the balance between genome
      integrity and cell cycle progression. However, the temporal order between these
      two events remains to be established.

PMID- 21959251
TI  - Nuclear positioning: mechanisms and functions.
AB  - The nucleus is the largest organelle in the cell and its position is dynamically
      controlled in space and time, although the functional significance of this
      dynamic regulation is not always clear. Nuclear movements are mediated by the
      cytoskeleton which transmits pushing or pulling forces onto the nuclear envelope.
      Recent studies have shed light on the mechanisms regulating nuclear positioning
      inside the cell. While microtubules have been known for a long time to be key
      players in nuclear positioning, the actin and cytoplasmic intermediate filament
      cytoskeletons have been implicated in this function more recently and various
      molecular links between the nuclear envelope and cytoplasmic elements have been
      identified. In this review, we summarize the recent advances in our understanding
      of the molecular mechanisms involved in the regulation of nuclear localization in
      various animal cells and give an overview of the evidence suggesting a crucial
      role of nuclear positioning in cell polarity and physiology and the consequences
      of nuclear mispositioning in human pathologies.

PMID- 21959252
TI  - Proteomics reveals a switch in CDK1-associated proteins upon M-phase exit during
      the Xenopus laevis oocyte to embryo transition.
AB  - Cyclin-dependent kinase 1 (CDK1) is a major M-phase kinase which requires the
      binding to a regulatory protein, Cyclin B, to be active. CDK1/Cyclin B complex is
      called M-phase promoting factor (MPF) for its key role in controlling both
      meiotic and mitotic M-phase of the cell cycle. CDK1 inactivation is necessary for
      oocyte activation and initiation of embryo development. This complex process
      requires both Cyclin B polyubiquitination and proteosomal degradation via the
      ubiquitin-conjugation pathway, followed by the dephosphorylation of the monomeric
      CDK1 on Thr161. Previous proteomic analyses revealed a number of CDK1-associated
      proteins in human HeLa cells. It is, however, unknown whether specific partners
      are involved in CDK1 inactivation upon M-phase exit. To better understand CDK1
      regulation during MII-arrest and oocyte activation, we immunoprecipitated (IPed)
      CDK1 together with its associated proteins from M-phase-arrested and M-phase
      exiting Xenopus laevis oocytes. A mass spectrometry (MS) analysis revealed a
      number of new putative CDK1 partners. Most importantly, the composition of the
      CDK1-associated complex changed rapidly during M-phase exit. Additionally, an
      analysis of CDK1 complexes precipitated with beads covered with p9 protein, a
      fission yeast suc1 homologue well known for its high affinity for CDKs, was
      performed to identify the most abundant proteins associated with CDK1. The screen
      was auto-validated by identification of: (i) two forms of CDK1: Cdc2A and B, (ii)
      a set of Cyclins B with clearly diminishing number of peptides identified upon M
      phase exit, (iii) a number of known CDK1 substrates (e.g. peroxiredoxine) and
      partners (e.g. HSPA8, a member of the HSP70 family) both in IP and in p9
      precipitated pellets. In IP samples we also identified chaperones, which can
      modulate CDK1 three-dimensional structure, as well as calcineurin, a protein
      necessary for successful oocyte activation. These results shed a new light on
      CDK1 regulation via a dynamic change in the composition of the protein complex
      upon M-phase exit and the oocyte to embryo transition.

PMID- 21959253
TI  - Microbiology goes big: microbial systems biology.

PMID- 21959254
TI  - Reliability and smallest real difference of the ankle lunge test post ankle
      fracture.
AB  - This study aimed to determine the reliability and the smallest real difference of
      the Ankle Lunge test in an ankle fracture patient population. In the post
      immobilisation stage of ankle fracture, ankle dorsiflexion is an important
      measure of progress and outcome. The Ankle Lunge test measures weight bearing
      dorsiflexion, resulting in negative scores (knee to wall distance) and positive
      scores (toe to wall distance), for which the latter has proven reliability in
      normal subjects only. A consecutive sample of ankle fracture patients with
      permission to commence weight bearing, were recruited to the study. Three
      measurements of the Ankle Lunge Test were performed each by two raters, one
      senior and one junior physiotherapist. These occurred prior to therapy sessions
      in the second week after plaster removal. A standardised testing station was
      utilised and allowed for both knee to wall distance and toe to wall distance
      measurement. Data was collected from 10 individuals with ankle fracture, with an
      average age of 36 years (SD 14.8). Seventy seven percent of observations were
      negative. Intra and inter-rater reliability yielded intra class correlations at
      or above 0.97, p < .001. There was a significant systematic bias towards improved
      scores during repeated measurement for one rater (p = .01). The smallest real
      difference was calculated as 13.8mm. The Ankle Lunge test is a practical and
      reliable tool for measuring weightbearing dorsiflexion post ankle fracture.

PMID- 21959255
TI  - Comparison of zotarolimus-eluting stents versus sirolimus-eluting stents versus
      paclitaxel-eluting stents for primary percutaneous coronary intervention in
      patients with ST-elevation myocardial infarction: results from the Korean
      Multicentre Endeavor (KOMER) acute myocardial infarction (AMI) trial.
AB  - AIMS: The aim of this study was to compare the efficacy and safety of zotarolimus
      eluting stents (ZES), sirolimus-eluting stents (SES) and paclitaxel-eluting
      stents (PES) in patients with ST-segment elevation myocardial infarction (STEMI)
      undergoing primary percutaneous coronary intervention (PCI). METHODS AND RESULTS:
      This study was a prospective, single-blind, multicentre, randomised trial. The
      primary endpoint was major adverse cardiac events (MACE) at 12 months post
      procedure, defined as cardiac death, recurrent myocardial infarction (MI), or
      ischaemia-driven target lesion revascularisation (TLR). An angiographic substudy
      was performed at nine months among 348 patients. From October 2006 to April 2008,
      611 patients with STEMI undergoing primary PCI were randomly assigned to
      treatment with ZES (n=205), SES (n=204), or PES (n=202). The cumulative incidence
      of MACE was 5.9% in the ZES group, 3.4% in the SES group and 5.7% in the PES
      group at 12-month follow-up (p=0.457). There was a trend towards a lower rate of
      ischaemia-driven TLR at 12- (p=0.092) and 18-month (p=0.080) follow-up in the SES
      group compared to the ZES and PES groups. No difference was observed in rates of
      cardiac death, recurrent MI and combined death and/or recurrent MI among three
      groups at 12- and 18-month follow-up. The rate of stent thrombosis was similar
      among the three groups (2.0% in each group, p=1.000). CONCLUSIONS: As compared
      with SES and PES, the use of ZES in patients with STEMI undergoing primary PCI,
      showed similar rates of MACE, cardiac death and recurrent MI at 12 and 18 months.
      There was a trend towards a higher rate of TLR with ZES or PES compared to SES.

PMID- 21959256
TI  - The metabolic syndrome, atherosclerosis and cognitive functioning in a non
      demented population: the Hoorn Study.
AB  - BACKGROUND: The metabolic syndrome (MetS) is associated with cognitive deficits
      and atherosclerotic vascular disease. We examined whether the relation between
      the MetS and cognitive dysfunction is mediated by measures of atherosclerosis or
      the presence of clinically manifest cardiovascular disease. METHODS: In 380
      individuals (153 with MetS; 60-87 years) from the population based Hoorn Study,
      measures of atherosclerosis including carotid intima-media thickness (c-IMT),
      flow mediated dilation (FMD), ankle-brachial index and the presence of clinically
      manifest cardiovascular disease were assessed at baseline and 7 later years at
      follow-up. Cognitive functioning (information processing speed, memory, and
      attention and executive functioning) was assessed at follow-up. The relation
      between the MetS, atherosclerosis and cognitive functioning was assessed with
      linear regression analysis. RESULTS: Individuals with MetS showed worse
      performance on information processing speed (adjusted mean difference z-score +/-
      SE: -0.22 +/- 0.6; p = 0.01) and attention and executive functioning (-0.32 +/-
      0.07; p < 0.001), but not on the domain memory. The affected cognitive domains
      were also associated with measures of atherosclerosis (standardised B (95%CI) c
      IMT: -0.14 (-0.24; -0.05); p < 0.01; FMD: 0.13 (0.02; 0.24), p < 0.05) and a
      history of clinically manifest cardiovascular disease: (-0.29 (-0.47; -0.11); p <
      0.01). However, the relation between the MetS and cognitive functioning did not
      change after adjustment for c-IMT, FMD or a history of clinically manifest
      cardiovascular disease (p > 0.05). CONCLUSION: In this population based cohort,
      the relation between the MetS and cognitive dysfunction was not mediated by
      atherosclerosis or a history of cardiovascular disease. These findings should
      stimulate future studies to elucidate alternative mechanisms underlying cognitive
      deficits in individuals with MetS.

PMID- 21959257
TI  - Increased glycosidic bond stabilities in 4-C-hydroxymethyl linked disaccharides.
AB  - Three new hydroxymethyl-linked non-natural disaccharide analogues, containing an
      additional methylene group in between the glycosidic linkage, were synthesized by
      utilizing 4-C-hydroxymethyl-alpha-d-glucopyranoside as the glycosyl donor. A
      kinetic study was undertaken to assess the hydrolytic stabilities of these new
      disaccharide analogues toward acid-catalyzed hydrolysis, at 60 degrees C and 70
      degrees C. The studies showed that the disaccharide analogues were stable, by an
      order of magnitude, than naturally-occurring disaccharides, such as, cellobiose,
      lactose, and maltose. The first order rate constants were lower than that of
      methyl glycosides and the trend of hydrolysis rate constants followed that of
      naturally-occurring disaccharides. alpha-Anomer showed faster hydrolysis than the
      beta-anomer and the presence of axial hydroxyl group also led to faster
      hydrolysis among the disaccharide analogues. Energy minimized structures, derived
      through molecular modeling, showed that dihedral angles around the glycosidic
      bond in disaccharide analogues were nearly similar to that of naturally-occurring
      disaccharides.

PMID- 21959258
TI  - Effect of Pam3Cys induced protection on the therapeutic efficacy of miltefosine
      against experimental visceral leishmaniasis.
AB  - Prophylactic potential of synthetic bacterial lipopeptide and a TLR2 agonist,
      Pam3Cys was first evaluated against experimental visceral leishmaniasis in rodent
      model. After establishing the potential its effect on therapeutic efficacy of
      miltefosine was also studied. Pam3Cys showed 74.64% inhibition in parasitic
      establishment when administered by ip route at a dose of 100 MUg/animal spaced at
      two weeks, i.e. on day -7 and +7 of challenge with Leishmania donovani
      amastigotes. However, when aforesaid dose of Pam3Cys was given with sub-curative
      dose of miltefosine (2.5 mg/kg for 5 days) its efficacy enhanced from 49.80% to
      92.25%. These findings revealed that this lipopeptide has potential protective
      efficacy which significantly enhanced the therapeutic efficacy of miltefosine
      used at low dose against Leishmania infection and warrants detailed
      investigations on its possible immunopotentiatory actions.

PMID- 21959259
TI  - Discontinuation of metformin in the setting of coronary angiography: clinical
      uncertainty amongst physicians reflecting a poor evidence base.
AB  - AIMS: Metformin is widely prescribed for the treatment of type 2 diabetes
      mellitus and is associated with a reduction in diabetes-induced cardiovascular
      morbidity and mortality. Concerns about metformin-associated lactic acidosis (M
      ALA) in patients undergoing contrast-based angiographic procedures have led to
      the development and publication of a number of guidelines to improve the
      management of this patient cohort. METHODS AND RESULTS: This review focuses on
      the evidence behind these guidelines and, in particular, that concerning
      metformin discontinuation in diabetic patients undergoing coronary angiography
      and percutaneous intervention. This review addresses and compares guideline
      directed management of such patients and includes the results of a UK physician
      survey to highlight variations in clinical practice. CONCLUSIONS: We conclude
      that evidence for M-ALA in diabetics on metformin undergoing coronary
      intervention is lacking and existing guidance on the management of such patients
      is inconsistent. More robust evidence is needed in the form of a large,
      adequately-sized randomised trial or extensive registry so that we can optimally
      manage those patients requiring contrast-based coronary interventions who are
      also taking metformin.

PMID- 21959260
TI  - Evaluation of dronedarone use in the US patient population between 2009 and 2010:
      a descriptive study using a claims database.
AB  - BACKGROUND: The utilization pattern of dronedarone was unknown, especially
      regarding prescribers' compliance with the product's prescribing information (PI)
      following its availability and the implementation of the Food and Drug
      Administration-approved risk evaluation and mitigation strategy for the drug in
      the United States. OBJECTIVE: This study was designed to evaluate the dronedarone
      prescribers' adherence to PI regarding the following contraindications: (1)
      patients with heart failure (HF) with a recent decompensation requiring
      hospitalization or referral to a specialist, (2) concomitant use of potent CYP3A4
      inhibitors, and (3) concomitant use of QT-prolonging drugs. METHODS: Patients
      prescribed dronedarone between July 2009 and August 2010 were identified through
      LabRx. The following rates surrounding dronedarone use were examined: (1) atrial
      fibrillation or atrial flutter in the past year, (2) worsening or hospitalization
      for HF within the month before prescription, and (3) concomitant prescription of
      potent CYP3A4 inhibitors and concomitant prescription of QT-prolonging drugs
      within the following month. RESULTS: A total of 4595 dronedarone prescriptions
      were filled by 1820 patients. More than 94% of the participants had >=1 diagnosis
      of atrial fibrillation or atrial flutter in the previous year. Worsening of or
      hospitalization for HF was found in 61 (3.4%) patients within the month before
      receiving dronedarone, including 18 patients with HF as the primary cause for
      hospitalization. Potent CYP3A4 inhibitors were prescribed to 10 (0.6%) patients
      within a month following dronedarone initiation, 6 of whom received them for
      topical use only. QT-prolonging drugs were prescribed to 67 (3.7%) patients
      within a month following dronedarone initiation, among which >90% were other
      antiarrhythmics. CONCLUSIONS: Dronedarone was used mostly in compliance with PI
      and risk evaluation and mitigation strategy in the studied population. In the
      LabRx database, dronedarone was commonly dispensed to patients with
      cardiovascular risk factors and rarely dispensed to patients with
      contraindications such as worsening HF or hospitalization for HF or with
      concomitant prescriptions of potent CYP3A4 inhibitors, QT-prolonging drugs, or
      both.

PMID- 21959261
TI  - Cyt1Aa toxin: crystal structure reveals implications for its membrane-perforating
      function.
AB  - During sporulation, Bacillus thuringiensis subsp. israelensis produces a mosquito
      larvicidal protein complex containing several crystalline and cytolytic (Cyt)
      toxins. Here, the activated monomeric form of Cyt1Aa, the most toxic Cyt family
      member, was isolated and crystallized, and its structure was determined for the
      first time at 2.2 A resolution. Cyt1Aa adopts a typical cytolysin fold containing
      a beta-sheet held by two surrounding alpha-helical layers. The absence of a beta
      strand (between residues V26 and I37) in the dimeric structure of Cyt2Aa led us
      to deduce that this is the only essential segment for dimer formation and that
      activation of the toxin occurs by proteolytic processing of its N-terminus. Based
      on the Cyt1Aa structure, we suggest that the toxicity of Cyt1Aa and other
      nonrelated proteins, all sharing a cytolysin fold, is correlated with their
      ability to undergo conformational changes that are necessary prior to their
      membrane insertion and perforation. This fold allows the alpha-helical layers to
      swing away, exposing the beta-sheet to insert into the membrane. The
      identification of a putative lipid binding pocket between the beta-sheet and the
      helical layer of Cyt1Aa supports this mechanism. Sequence-based structural
      analysis of Cyt1Aa revealed that the lack of activity of Cyt1Ca may be related to
      the latter's inability to undergo this conformational change due to its lack of
      flexibility. The pattern of the hemolytic activity of Cyt1Aa presented here
      (resembling that of pore-forming agents), while differing from that imposed by
      ionic and nonionic detergents, further supports the pore-forming model by which
      conformational changes occur prior to membrane insertion and perforation.

PMID- 21959262
TI  - A molecular model of phosphorylation-based activation and potentiation of
      tarantula muscle thick filaments.
AB  - Myosin filaments from many muscles are activated by phosphorylation of their
      regulatory light chains (RLCs). To elucidate the structural mechanism of
      activation, we have studied RLC phosphorylation in tarantula thick filaments,
      whose high-resolution structure is known. In the relaxed state, tarantula RLCs
      are ~50% non-phosphorylated and 50% mono-phosphorylated, while on activation,
      mono-phosphorylation increases, and some RLCs become bi-phosphorylated. Mass
      spectrometry shows that relaxed-state mono-phosphorylation occurs on Ser35, while
      Ca(2+)-activated phosphorylation is on Ser45, both located near the RLC N
      terminus. The sequences around these serines suggest that they are the targets
      for protein kinase C and myosin light chain kinase (MLCK), respectively. The
      atomic model of the tarantula filament shows that the two myosin heads ("free"
      and "blocked") are in different environments, with only the free head serines
      readily accessible to kinases. Thus, protein kinase C Ser35 mono-phosphorylation
      in relaxed filaments would occur only on the free heads. Structural
      considerations suggest that these heads are less strongly bound to the filament
      backbone and may oscillate occasionally between attached and detached states
      ("swaying" heads). These heads would be available for immediate actin interaction
      upon Ca(2)(+) activation of the thin filaments. Once MLCK becomes activated, it
      phosphorylates free heads on Ser45. These heads become fully mobile, exposing
      blocked head Ser45 to MLCK. This would release the blocked heads, allowing their
      interaction with actin. On this model, twitch force would be produced by rapid
      interaction of swaying free heads with activated thin filaments, while prolonged
      exposure to Ca(2+) on tetanus would recruit new MLCK-activated heads, resulting
      in force potentiation.

PMID- 21959263
TI  - Molecular basis for herpesvirus entry mediator recognition by the human immune
      inhibitory receptor CD160 and its relationship to the cosignaling molecules BTLA
      and LIGHT.
AB  - CD160 was recently identified as a T cell coinhibitory molecule that interacts
      with the herpesvirus entry mediator (HVEM) on antigen-presenting cells to deliver
      a potent inhibitory signal to CD4(+) T cells. HVEM also binds to the coinhibitory
      receptor BTLA (B- and T-lymphocyte attenuator) and the costimulatory receptor
      LIGHT (which is homologous to lymphotoxins, exhibits inducible expression, and
      competes with the herpes simplex virus glycoprotein D for HVEM, a receptor
      expressed by T lymphocytes, or TNFSF14), thus regulating the
      CD160/BTLA/LIGHT/HVEM signaling pathway. To date, the detailed properties of the
      formation of these complexes, especially HVEM binding to the newly identified
      receptor CD160, and the relationship of CD160 with BTLA and LIGHT are still
      unclear. We performed N-terminal sequencing and a mass spectrometric analysis,
      which revealed that the extracellular domain of CD160 exists primarily in the
      monomeric form. The surface plasmon resonance analysis revealed that CD160 binds
      directly to the cysteine-rich domain 1-3 of HVEM with a similar affinity to, but
      slower dissociation rate than, that of BTLA. Notably, CD160 competed with BTLA
      for binding to HVEM; in contrast, LIGHT did not affect HVEM binding to either
      CD160 or BTLA. The results of a mutagenesis study of HVEM also suggest that the
      CD160 binding region on HVEM was slightly different from, but overlapped with,
      the BTLA binding site. Interestingly, an anti-CD160 antibody exhibiting
      antiangiogenic properties blocked CD160/HVEM binding. These results provide
      insight into the molecular architecture of the CD160/BTLA/LIGHT/HVEM signaling
      complex that regulates immune function.

PMID- 21959264
TI  - Crystal structures of mouse and human RP105/MD-1 complexes reveal unique dimer
      organization of the toll-like receptor family.
AB  - The Toll-like receptor (TLR) 4/MD-2 heterodimer senses lipopolysaccharide (LPS).
      RP105 (radioprotective 105 kDa), a TLR-related molecule, is similar to TLR4 in
      that the extracellular leucine-rich repeats associate with MD-1, the MD-2-like
      molecule. MD-2 has a unique hydrophobic cavity that directly binds to lipid A,
      the active center of LPS. LPS-bound MD-2 opens the secondary interface with TLR4,
      leading to dimerization of TLR4/MD-2. MD-1 also has a hydrophobic cavity that
      accommodates lipid IVa, a precursor of lipid A, suggesting a role for the
      RP105/MD-1 heterodimer in sensing LPS or related microbial products. Little is
      known, however, about the structure of the RP105/MD-1 heterodimer or its
      oligomer. Here, we have determined the crystal structures of mouse and human
      RP105/MD-1 complexes at 1.9 and 2.8 A resolutions, respectively. Both mouse and
      human RP105/MD-1 exhibit dimerization of the 1:1 RP105/MD-1 complex,
      demonstrating a novel organization. The "m"-shaped 2:2 RP105/MD-1 complex
      exhibits an inverse arrangement, with N-termini interacting in the middle. Thus,
      the dimerization interface of RP105/MD-1 is located on the opposite side of the
      complex, compared to the 2:2 TLR4/MD-2 complex. These results demonstrate that
      the 2:2 RP105/MD-1 complex is distinct from previously reported TLR dimers,
      including TLR4/MD-2, TLR1/TLR2, TLR2/TLR6, and TLR3, all of which facilitate
      homotypic or heterotypic interaction of the C-terminal cytoplasmic signaling
      domain.

PMID- 21959265
TI  - Incidence and outcome of out-of-hospital cardiac arrest with public-access
      defibrillation. A descriptive epidemiological study in a large urban community.
AB  - BACKGROUND: Detailed characteristics of those who experience an out-of-hospital
      cardiac arrest (OHCA) with public-access defibrillation (PAD) are unknown.
      METHODS AND RESULTS: A prospective, population-based observational study
      involving consecutive OHCA patients with emergency responder resuscitation
      attempts was conducted from July 1, 2004 through December 31, 2008 in Osaka City.
      We extracted data for OHCA patients shocked by a public-access automated external
      defibrillator (AED) and evaluated the patients' and rescuers' characteristics.
      The main outcome measure was neurologically favorable 1-month survival. During
      the study period, 10,375 OHCA patients were registered and of 908 patients
      suffering ventricular fibrillation arrest, 53 (6%) received public-access AED
      shocks by lay-rescuers, with the proportion increasing from 0% in 2004 to 11% in
      2008 (P for trend<0.001). Railway stations (34%) were the places where PAD shocks
      were most frequently delivered, followed by nursing homes (11%), medical
      facilities (9%), and fitness facilities (7%). In 57% of cases, the subject
      received public-access AED shocks delivered by non-medical persons, including
      employees of railway companies (13%), school teachers (6%), employees of fitness
      facilities (6%), and security guards (6%). The proportion of neurologically
      favorable 1-month survival tended to increase from 0% in 2005 to 58% in 2008 (P
      for trend=0.081). CONCLUSIONS: Railway stations are the most common places where
      shocks by public-access AEDs were delivered in large urban communities of Japan,
      and among lay-rescuers railway station workers use AEDs more frequently.

PMID- 21959266
TI  - Analysis of the risk associated with pregnancy in women with marfan syndrome.

PMID- 21959268
TI  - "Twisted" scorpionates: synthesis of a tris(2-pyridonyl)borate (Thp) ligand;
      lessons in the requirements for successful B(L2D)3 type ligands.
AB  - The synthesis of a new charge-neutral zwitterionic tripodal borate ligand based
      on 2-hydroxypyridine is reported. (Dimethylaminopyridinium)tris(2
      pyridonyl)borate, (DMAP)Thp, has been complexed to copper(I) chloride to give a
      pseudo-C(3) symmetric complex. The propensity for this ligand and other flexible
      scorpionates to exhibit such helical chirality upon complexation is discussed.

PMID- 21959267
TI  - Patient and public involvement in clinical practice guidelines: a knowledge
      synthesis of existing programs.
AB  - BACKGROUND: Reviewers independently extracted data on key components of PPIPs and
      barriers and facilitators to their operation. Data synthesis. Over half of the
      studies were published after 2002, and more than half originated from the United
      States, the United Kingdom, Australia, and Germany. CPGs that involved patients
      and the public addressed a variety of health problems, especially mental health
      and cancer. The most frequently cited objective for using PPIPs in developing
      CPGs was to incorporate patients' values or perspectives in CPG recommendations.
      Patients and their families and caregivers were the parties most often involved.
      METHODS: used to recruit PPIP participants included soliciting through
      patient/public organizations, sending invitations, and receiving referrals and
      recruits from clinicians. Patients and the public most often participated by
      taking part in a CPG working group, workshop, meeting, seminar, literature
      review, or consultation such as a focus group, individual interview, or survey.
      Patients and the public principally helped formulate recommendations and revise
      drafts. Limitations. The authors did not contact the authors of the studies.
      CONCLUSION: This literature review provides an extensive knowledge base for
      making PPIPs more effective when developing and implementing CPGs. More research
      is needed to assess the impact of PPIPs and resources they require.

PMID- 21959269
TI  - MCAM-expressing CD4(+) T cells in peripheral blood secrete IL-17A and are
      significantly elevated in inflammatory autoimmune diseases.
AB  - Th17 cells are a subset of CD4(+) T cells characterized by production of IL-17
      and are known to be key participants in inflammatory reactions and various
      autoimmune diseases. In this study we found that a subset of human CD4(+) T cells
      expressing MCAM (CD146) have higher mRNA levels of RORC2, IL-23R, IL-26, IL-22,
      IL-17A, but not IFN-gamma, compared to CD4(+) T cell not expressing CD146. Upon
      TCR stimulation with CD3/CD28, CD4(+)CD146(+) T cells secrete significantly more
      IL-17A, IL-6, and IL-8 than do CD4(+)CD146(-) T cells. Low frequencies of
      CD4(+)CD146(+) T cells are found in the circulation of healthy adults, but the
      frequency of these cells is significantly increased in the circulation of
      patients with inflammatory autoimmune diseases including Behcet's, sarcoidosis
      and Crohn's disease. Patterns of gene expression and cytokine secretion in these
      cells are similar in healthy and disease groups. In Crohn's disease, the increase
      in CD4(+)CD146(+) cells in the circulation correlates with disease severity
      scores. These data indicate that expression of CD146 on CD4(+) T cells identifies
      a population of committed human Th17 cells. It is likely the expression of CD146,
      an endothelial adhesion molecule, facilitates adherence and migration of Th17
      cells through the endothelium to sites of inflammation.

PMID- 21959270
TI  - Vocal fold cancer.
AB  - Ninety percent of vocal fold cancers take the form of squamous cell carcinoma.
      Since the 1980s, incidence in France has been constantly falling in males while
      increasing in females. The main risk factor is smoking, alcohol being less
      implicated than in other laryngeal or extralaryngeal locations. Vocal fold
      squamous cell carcinoma generally develops on healthy mucosa, although primary
      precancerous lesions such as leukoplakia or papillomatous keratosis are also
      frequent. The tumor usually originates in the non-lymphophilic mucosal free edge
      of the vocal fold then invades the various anatomic subunits of the larynx,
      acquiring lymph-node metastatic potential. Dysphonia is the first presenting
      symptom, initially caused by defective mucosal vibration and then by impaired
      mobility and finally fixation of the vocal fold. Extension, risk factor and
      pretreatment assessments are as in other upper-aerodigestive-tract cancer
      locations. The possibilities of laryngoscopic exposure and the tumor limits,
      however, need to be precisely determined if transoral resection is to be
      considered. For small tumors, surgery or exclusive radiation therapy can be
      suggested to the patient as part of an individual treatment plan, each having its
      advantages and drawbacks. Cutting-edge teams report 5-year local control rates of
      85-95% in T1-class tumor and 60-90% in T2. Whatever the treatment option, smoking
      cessation, close surveillance and cardiovascular prevention enable screening of
      other oncologic locations and limit onset of the other pathologies implicated in
      most deaths.

PMID- 21959271
TI  - Where will new neuroscience therapies come from?
AB  - The challenges of developing drugs for central nervous system disorders have led
      some major companies to reduce or discontinue investment in the field, even
      though the unmet medical need is substantial. How can the wealth of basic
      research knowledge in neuroscience be successfully translated into new therapies?

PMID- 21959272
TI  - Companies hope for kinase inhibitor JAKpot.

PMID- 21959273
TI  - Gene therapies advance towards finish line.

PMID- 21959279
TI  - Paul Brown. Interview by Asher Mullard.

PMID- 21959280
TI  - Antibacterial R&D incentives.

PMID- 21959281
TI  - Ezogabine (retigabine).
AB  - Ezogabine (Potiga; Valeant Pharmaceuticals/GlaxoSmithKline), a potassium channel
      opener, was approved in June 2011 by the U.S. Food and Drug Administration
      (F.D.A.) for the adjunctive treatment of partial-onset seizures in adult
      patients. The same drug was granted marketing authorization for this indication
      in the European Union in March 2011, where it is known as retigabine (Trobalt).

PMID- 21959282
TI  - Achilles heel of Ebola viral entry.

PMID- 21959283
TI  - Targeting MYC? You BET.

PMID- 21959284
TI  - New clues for flu vaccine design.

PMID- 21959286
TI  - A sweet blow for cancer cells.

PMID- 21959287
TI  - Integrating predictive biomarkers and classifiers into oncology clinical
      development programmes.
AB  - The future of drug development in oncology lies in identifying subsets of
      patients who will benefit from particular therapies, using predictive biomarkers.
      These technologies offer hope of enhancing the value of cancer medicines and
      reducing the size, cost and failure rates of clinical trials. However, examples
      of the failure of predictive biomarkers also exist. In these cases the use of
      biomarkers increased the costs, complexity and duration of clinical trials, and
      narrowed the treated population unnecessarily. Here, we present methods to
      adaptively integrate predictive biomarkers into clinical programmes in a data
      driven manner, wherein these biomarkers are emphasized in exact proportion to the
      evidence supporting their clinical predictive value. The resulting programme
      demands value from predictive biomarkers and is designed to optimally harvest
      this value for oncology drug development.

PMID- 21959288
TI  - The influence of the 'organizational factor' on compound quality in drug
      discovery.
AB  - Physicochemical properties such as lipophilicity and molecular mass are known to
      have an important influence on the absorption, distribution, metabolism,
      excretion and toxicity (ADMET) profile of small-molecule drug candidates. To
      assess the use of this knowledge in reducing the likelihood of compound-related
      attrition, the molecular properties of compounds acting at specific drug targets
      described in patents from leading pharmaceutical companies during the 2000-2010
      period were analysed. Over the past decade, there has been little overall change
      in properties that influence ADMET outcomes, but there are marked differences in
      molecular properties between organizations, which are maintained when the targets
      pursued are taken into account. The target-unbiased molecular property
      differences, which are attributable to divergent corporate drug design
      strategies, are comparable to the differences between the major drug target
      classes. On the basis of our analysis, we conclude that a substantial sector of
      the pharmaceutical industry has not modified its drug design practices and is
      still producing compounds with suboptimal physicochemical profiles.

PMID- 21959289
TI  - Defluviimonas denitrificans gen. nov., sp. nov., and Pararhodobacter aggregans
      gen. nov., sp. nov., non-phototrophic Rhodobacteraceae from the biofilter of a
      marine aquaculture.
AB  - Three Gram-negative bacterial strains were isolated from the biofilter of a
      recirculating marine aquaculture. They were non-pigmented rods, mesophiles,
      moderately halophilic, and showed chemo-organoheterotrophic growth on various
      sugars, fatty acids, and amino acids, with oxygen as electron acceptor; strains
      D9-3(T) and D11-58 were in addition able to denitrify. Phototrophic or
      fermentative growth could not be demonstrated. Phylogenetic analysis of the 16S
      rRNA gene sequences placed D9-3(T) and D11-58, and D1-19(T) on two distinct
      branches within the alpha-3 proteobacterial Rhodobacteraceae, affiliated with,
      but clearly separate from, the genera Rhodobacter, Rhodovulum, and Rhodobaca.
      Based on morphological, physiological, and 16S rRNA-based phylogenetic
      characteristics, the isolated strains are proposed as new species of two novel
      genera, Defluviimonas denitrificans gen. nov., sp. nov. (type strain D9-3(T)=DSM
      18921(T)=ATCC BAA-1447(T); additional strain D11-58=DSM19039=ATCC BAA-1448) and
      Pararhodobacter aggregans gen. nov., sp. nov (type strain D1-19(T)=DSM
      18938(T)=ATCC BAA-1446(T)).

PMID- 21959290
TI  - "To be or not to be," ten years after: evidence for mixed connective tissue
      disease as a distinct entity.
AB  - OBJECTIVES: To determine if mixed connective tissue disease (MCTD) can be
      considered an independent clinical entity, to compare 3 different classification
      criteria for MCTD (Kasukawa, Alarcon-Segovia, and Sharp), and to define
      predictors (clinical features and autoantibodies) of potential evolution toward
      other connective tissue diseases (CTDs). METHODS: One hundred sixty-one MCTD
      patients were evaluated retrospectively at the diagnosis and in 2008. They were
      classified, at the diagnosis, according to the 3 classification criteria of MCTD
      (Sharp, Alarcon-Segovia, and Kasukawa) and reclassified in 2008 according to
      their evolution. Statistical analyses were performed to find out predictors
      (clinical features and autoantibodies) of evolution into other CTDs. RESULTS:
      After a mean of 7.9 years of disease, 57.9% of patients still satisfied MCTD
      classification criteria of Kasukawa; 17.3% evolved into systemic sclerosis, 9.1%
      into systemic lupus erythematosus, 2.5% into rheumatoid arthritis, 11.5% was
      reclassified as affected by undifferentiated connective tissue disease, and 1.7%
      as suffering from overlap syndrome. Kasukawa's criteria were more sensitive (75%)
      in comparison to those of Alarcon-Segovia (73%) and Sharp (42%). The presence of
      anti-DNA antibodies (P = 0.012) was associated with evolution into systemic lupus
      erythematosus; hypomotility or dilation of esophagus (P < 0.001); and
      sclerodactyly (P = 0.034) with evolution into systemic sclerosis. CONCLUSIONS:
      MCTD is a distinct clinical entity but it is evident that a subgroup of patients
      may evolve into another CTD during disease progression. Initial clinical features
      and autoantibodies can be useful to predict disease evolution.

PMID- 21959291
TI  - Primary prophylaxis for Pneumocystis jirovecii pneumonia in patients with
      connective tissue diseases.
AB  - OBJECTIVES: The aim of our study was to examine the primary prophylactic effect
      of sulfamethoxazole/trimethoprim single strength (SMZ/TM SS) against Pneumocystis
      jirovecii pneumonia (PCP) in connective tissue disease (CTD) patients with immune
      dysfunction induced by the long-term use of prednisolone. Prevalence of adverse
      drug reactions (ADRs) to sulfonamide in these patients was the secondary outcome.
      METHODS: This was a retrospective cohort study. Medical records of CTD patients
      who were treated with prednisolone >=20 mg per day or equivalent doses of
      corticosteroid for more than 2 weeks and were followed for at least 12 weeks
      after receiving this dosage of corticosteroids at the Rheumatology clinic of
      Ramathibodi Hospital between October 2006 and September 2007 were reviewed.
      Information regarding clinical status, laboratory features, and clinical course
      of the enrolled subjects was recorded. RESULTS: There were 138 episodes of PCP
      risk in 132 CTD patients; 59 episodes received SMZ/TM SS, while 79 episodes did
      not. All 6 PCP cases developed in patients without prophylaxis with an overall
      incidence of 4.3%. The incidence of PCP between the 2 groups was significantly
      different (P = 0.038). Absolute risk reduction and relative risk reduction were
      7.3% and 100%, respectively. All ADR developed in 5 systemic lupus erythematosus
      patients (8.5%): 4 had drug rashes and 1 had mild hepatitis. There was no
      correlation between the use of, or allergic reactions to, SMZ/TM and lupus flare.
      CONCLUSIONS: Sulfamethoxazole/trimethoprim single strength can be used
      effectively as a primary prophylaxis against PCP in high-risk CTD patients. Only
      mild ADR developed at this dosage. Further evaluations in larger groups of CTD
      patients are warranted.

PMID- 21959292
TI  - Paget's disease of bone: evidence for complex pathogenetic interactions.
AB  - OBJECTIVES: Paget's disease of bone (PDB), with a prevalence of 2 to 5% in
      Caucasians >55 years, is the second most frequent metabolic bone disease, after
      osteoporosis. PDB characteristics are bone lesions with an imbalanced bone
      remodeling, resulting in disorganized and nonfully fledged new bone. PDB etiology
      is not completely understood. In this review, current views on the etiology,
      clinical aspects, and PDB treatment are summarized and discussed. METHODS: The
      PubMed database was searched using the keywords PDB, sequestosome1 (SQSTM1),
      valosin-containing protein (VCP), receptor activator of nuclear factor-kappaB
      (RANK), osteoprotegerin (OPG), RANK ligand (RANKL), mutation, genetic variants,
      virus, osteosarcoma, bisphosphonates, and denosumab. RESULTS: Environmental
      evidence (e.g. viruses) and also genetic risk factors have been found for PDB.
      Until now, SQSTM1 was the only PDB-causing gene identified. However, PDB patients
      without SQSTM1 mutations seem to have susceptibility genetic polymorphisms in
      regions containing the CaSR, ESR1, TNFRSF11B (OPG), TNFRSF11A (RANK), CSF1 (M
      CSF), OPTN, TM7SF4 (DC-STAMP), VCP, NUP205, RIN3, PML, and GOLGA6A genes,
      resulting in an increased risk of developing PDB. The nature of these genes
      indicates that the regulation of osteoclastogenesis is a key process in PDB
      pathogenesis. Furthermore, with the involvement of SQSTM1 and VCP in autophagy
      and in forming protein aggregates, this might also indicate that a disturbance of
      these processes might be a risk factor. CONCLUSIONS: Unraveling the PDB genetic
      background is instrumental to understanding the PDB pathogenesis and the role of
      slow viruses. Furthermore, it might make early detection and subsequently
      treatment of risk individuals possible.

PMID- 21959293
TI  - Synthesis and evaluation of poly(hexamethylene-urethane) and PEG
      poly(hexamethylene-urethane) and their cholesteryl oleyl carbonate composites for
      human blood biocompatibility.
AB  - Two new urethane-based acrylates (UAA and PEG-UAA) were synthesized as polymer
      blocks. The chemical composition of the two monomers was confirmed by IR and NMR.
      After cross-linking these blockers by radical polymerization, "hexamethylene PU"
      [poly(hexamethylene-urethane)] and "PEG-hexamethylene PU" [PEG-poly(hexa
      methylene-urethane)] were obtained. The platelet adhesion and platelet activation
      of these polymers were evaluated in the presence of Platelet Rich Plasma (PRP)
      blood. The relative blood clotting indexes of the polymers were determined to
      measure their capability of reducing thrombogenicity. The hemolysis of red blood
      cells was also assessed to examine the haemocompatibility of the polymers. The
      hexamethylene PU and PEG-hexamethylene PU showed less platelet adhesion, platelet
      activation, blood clotting and hemolysis than a commercial PU (Tecoflex). The
      liquid crystal molecule, cholesteryl oleyl carbonate (COC), showed further
      improved biocompatibility to human blood, after COC was embedded in the PU
      polymers. PEG-hexamethylene PU + 10% COC demonstrated the best activity in
      reducing thrombogenicity and the best haemocompatibility. The inclusion of PEG
      segments into the PEG-UAA structure increased its hydrophilicity. The methylene
      bis(cyclohexyl) segments in Tecoflex PU decreased haemocompatibility. These
      observations are in good agreement with performed contact angle measurements. The
      PEG-hexamethylene PU loaded with COC might be a promising material for
      applications in bioengineering.

PMID- 21959294
TI  - HPLC determination of antilipoxygenase activity of a water infusion of Ligustrum
      vulgare L. leaves and some of its constituents.
AB  - The aim of the study was a HPLC evaluation of the lipoxygenase activity
      inhibiting activity of a water infusion of Ligustrum vulgare L. leaves and
      selected isolates from it. The antiradical activity of the water infusion was
      determined using DPPH, ABTS and FRAP tests. Oleuropein and echinacoside
      concentrations in the water infusion were determined by HPLC. Water infusion,
      echinacoside and oleuropein were used for an antilipoxygenase activity assay
      using lipoxygenase isolated from rat lung cytosol fraction. Activity of 8-LOX, 12
      LOX and 15-LOX were monitored through formation of 8-HETE, 12-HETE and 15-HETE,
      respectively. The water infusion exhibited the highest activity against all
      lipoxygenases, followed by oleuropein. Echinacoside was ineffective against LOXs
      in lower concentrations, while higher concentration showed similar inhibition on
      8-LOX and 12-LOX. 15-LOX was affected more and the presence of echinacoside
      remarkably decreased its activity.

PMID- 21959295
TI  - Gold nanoparticle-catalyzed environmentally benign deoxygenation of epoxides to
      alkenes.
AB  - We have developed a highly efficient and green catalytic deoxygenation of
      epoxides to alkenes using gold nanoparticles (NPs) supported on hydrotalcite [HT:
      Mg(6)Al(2)CO(3)(OH)(16)] (Au/HT) with alcohols, CO/H(2)O or H(2) as the reducing
      reagent. Various epoxides were selectively converted to the corresponding
      alkenes. Among the novel metal NPs on HT, Au/HT was found to exhibit outstanding
      catalytic activity for the deoxygenation reaction. Moreover, Au/HT can be
      separated from the reaction mixture and reused with retention of its catalytic
      activity and selectivity. The high catalytic performance of Au/HT was attributed
      to the selective formation of Au-hydride species by the cooperative effect
      between Au NPs and HT.

PMID- 21959296
TI  - SFE-CO2 extract from Typhonium giganteum Engl. tubers, induces apoptosis in human
      hepatoma SMMC-7721 cells involvement of a ROS-mediated mitochondrial pathway.
AB  - Typhonium giganteum Engl. (BaiFuzi) is one of the herbs commonly used in
      traditional Chinese medicine against cancer. In our previous studies, 37
      compounds were identified the SFE-CO(2) (supercritical fluid extraction with
      CO(2)) extract by GC-MS, including the four major components [beta-sitosterol
      (40.22%), campesterol (18.45%), n-hexadecanoic acid (9.52%) and (Z,Z)-9,12
      octadecadienoic acid (8.15%)]. The anti-cancer mechanisms of the SFE-CO(2
      )extract from T. giganteum Engl. tubers have not been reported as yet. In this
      paper, the molecular mechanisms of the SFE-CO(2) extract-mediated apoptosis in
      SMMC-7721 cells were further examined. SFE-CO(2) extract inhibited the growth of
      SMMC-7721 cells in a time- and dose-dependent manner, arrested the cell cycle in
      the S phase and G2/M phase, and induced apoptosis. In addition, reactive oxygen
      species (ROS) increase, reduction of mitochondrial membrane potential, a rise in
      intracellular calcium levels were found in SMMC-7721 cells after treated with the
      extract. Western blot analysis showed that the extract caused down-regulation of
      Bcl-2 expression, and up-regulation of Bax expression. Moreover, caspase-3 and
      caspase-9 protease activity significantly increased in a dose-dependent manner.
      Collectively, our results showed that the SFE-CO(2) extract from T. giganteum
      Engl. tubers induces apoptosis in SMMC-7721 cells involving a ROS-mediated
      mitochondrial signalling pathway.

PMID- 21959297
TI  - Synthesis under microwave irradiation of [1,2,4]triazolo[3,4-b]
      [1,3,4]thiadiazoles and other diazoles bearing indole moieties and their
      antimicrobial evaluation.
AB  - Microwave-assisted synthesis of some novel compounds, namely, 3-(2-methyl-1H
      indol-3-yl)-6-aryl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles 5a,b was
      accomplished via bromination of 2-methyl-3-[4-(arylideneamino)-5-mercapto-4H
      [1,2,4]triazol-3-yl]-1H-indoles 3a,b. Also, new [1,3,4]thiadiazoles 12a,b,
      [1,2,4]triazoles 15a,b and [1,3,4]oxadiazoles 19a,b, with indole moieties, were
      prepared by cyclization of 1-[(2-methyl-1H-indole)-3-carbonyl]thiosemicarbazides
      8a,b under microwave irradiation using different reaction conditions. Moreover,
      reaction of acid hydrazide 7 with ethyl 2-(N-phenylhydrazono)-3-oxobutanoate (20)
      gave the respective phenylhydrazonopyrazole derivative 21 under the reaction
      conditions employed. The structures of the synthesized compounds were assigned
      based on elemental analyses and spectral data (IR, (1)H-NMR, (13)C-NMR, MS). The
      antifungal and antibacterial activities of the new products were also evaluated.

PMID- 21959298
TI  - Flavonoids as vasorelaxant agents: synthesis, biological evaluation and
      quantitative structure activities relationship (QSAR) studies.
AB  - A series of 2-(2-diethylamino)-ethoxychalcone and 6-prenyl(or its isomers)
      flavanones 10a,b and 11a-g were synthesized and evaluated for their vasorelaxant
      activities against rat aorta rings pretreated with 1 MUM phenylephrine (PE).
      Several compounds showed potent vasorelaxant activities. Compound 10a (EC(50) =
      7.6 MUM, E(max) = 93.1%), the most potent one, would be a promising structural
      template for development of novel and more efficient vasodilators. Further, 2D
      QSAR analysis of compounds 10a,b and 11c-e as well as thirty previously
      synthesized flavonoids 1-3 and 12-38 using Enhanced Replacement Method-Multiple
      Linear Regression (ERM-MLR) was further performed based on an optimal set of
      molecular descriptors (H5m, SIC2, DISPe, Mor03u and L3m), leading to a reliable
      model with good predictive ability (R(train)(2) = 0.839, Q(loo)(2) = 0.733 and
      R(test)(2) = 0.804). The results provide good insights into the structure-
      activity relationships of the target compounds.

PMID- 21959299
TI  - Helichrysum gymnocephalum essential oil: chemical composition and cytotoxic,
      antimalarial and antioxidant activities, attribution of the activity origin by
      correlations.
AB  - Helichrysum gymnocephalum essential oil (EO) was prepared by hydrodistillation of
      its leaves and characterized by GC-MS and quantified by GC-FID. Twenty three
      compounds were identified. 1,8-Cineole (47.4%), bicyclosesquiphellandrene (5.6%),
      gamma-curcumene (5.6%), alpha-amorphene (5.1%) and bicyclogermacrene (5%) were
      the main components. Our results confirmed the important chemical variability of
      H. gymnocephalum. The essential oil was tested in vitro for cytotoxic (on human
      breast cancer cells MCF-7), antimalarial (Plasmodium falciparum: FcB1-Columbia
      strain, chloroquine-resistant) and antioxidant (ABTS and DPPH assays) activities.
      H. gymnocephalum EO was found to be active against MCF-7 cells, with an IC(50) of
      16 +/- 2 mg/L. The essential oil was active against P. falciparum (IC(50) = 25 +/
      1 mg/L). However, the essential oil exhibited a poor antioxidant activity in the
      DPPH (IC(50) value > 1,000 mg/L) and ABTS (IC(50) value = 1,487.67 +/- 47.70
      mg/L) assays. We have reviewed the existing results on the anticancer activity of
      essential oils on MCF-7 cell line and on their antiplasmodial activity against
      the P. falciparum. The aim was to establish correlations between the identified
      compounds and their biological activities (antiplasmodial and anticancer). beta
      Selinene (R2 = 0.76), alpha-terpinolene (R2 = 0.88) and aromadendrene (R2 = 0.90)
      presented a higher relationship with the anti-cancer activity. However, only
      calamenene (R2 = 0.70) showed a significant correlation for the antiplasmodial
      activity.

PMID- 21959300
TI  - Antihyperlipidemic properties of novel N-(benzoylphenyl)-5-substituted-1H-indole
      2-carboxamides in Triton WR-1339-induced hyperlipidemic rats.
AB  - In the search for new potential antihyperlipidemic agents, the present study
      focuses on the synthesis of novel N-(benzoylphenyl)-5-substituted-1H-indole-2
      carboxamides (compounds 8-12, 15, 16, 18) and investigating their
      antihyperlipidemic activity using Triton WR-1339-induced hyperlipidemic rats as
      an experimental model. Hyperlipidemia was developed by intraperitoneal injection
      of Triton WR-1339 (250 mg/kg body weight). The tested animals were divided into
      normal control (NCG), hyperlipidemic (HG), compound 8, 9, 15, 16, 18- and
      bezafibrate treated groups. At a dose of 15 mg/kg body weight, compounds 9, 16,
      18 and bezafibrate (100 mg/kg) significantly (p < 0.0001) reduced elevated plasma
      triglycerides levels after 12 h compared to the hyperlipidemic control group.
      However, only the group treated with compounds 9, 16 and 18 showed an obviously
      significant (p < 0.001) reduction in plasma total cholesterol levels after 12 h
      compared to the hyperlipidemic control group. Moreover, high density lipoprotein
      cholesterol levels were significantly (p < 0.0001) increased in all treated
      groups after 12 h compared to the hyperlipidemic control group, except for
      compounds 8 and 15 which revealed inactive. It is therefore reasonable to assume
      that compounds 9, 16 and 18 may have potential in the treatment of
      hyperlipidemia.

PMID- 21959301
TI  - Inhibitory effects of constituents from Euphorbia lunulata on differentiation of
      3T3-L1 cells and nitric oxide production in RAW264.7 cells.
AB  - A new flavonol galactopyranoside, myricetin 3-O-(2'',3''-digalloyl)-beta-D
      galactopyranoide (1), and 23 known constituents, including myricetin 3-O-(2''
      galloyl)-beta-D-galactopyranoide (2), myricitrin (3), myricetin (4), quercetin 3
      O-(2'', 3''-digalloyl)-beta-D-galactopyranoide (5), quercetin 3-O-(2''-galloyl)
      beta-D-galactopyranoide (6), hyperin (7), isoquercetrin (8), quercetin (9),
      kaempferol (10), apigenin (11), luteolin (12), 3-O-methylquercetin (13),
      5,7,2',5'-tetrahydroxyflavone (14), 1,3,4,6-tetra-O-galloyl-beta-D-glucose (15),
      1,2,6-tri-O-galloyl-beta-D-glucose (16), 1,3,6-tri-O-galloyl-beta-D-glucose (17),
      gallic acid (18), protocatechuic acid (19), 3,4,5-trimethoxybenzoic acid (20),
      2,6-dihydroxyacetophenone (21), 3,3'-di-O-methylellagic acid (22), ellagic acid
      (23) and esculetin (24) were isolated from Euphorbia lunulata Bge. Their
      structures were determined by spectroscopic analysis. Isolated hydrolysable
      tannins, flavonoids, and flavonol galactopyranoside gallates showed significant
      inhibition of the differentiation of 3T3-L1 preadipocytes and triglyceride
      accumulation in maturing adipocytes, and nitric oxide production in RAW 264.7
      cells.

PMID- 21959302
TI  - Role of Kupffer cells in thioacetamide-induced cell cycle dysfunction.
AB  - It is well known that gadolinium chloride (GD) attenuates drug-induced
      hepatotoxicity by selectively inactivating Kupffer cells. In the present study
      the effect of GD in reference to cell cycle and postnecrotic liver regeneration
      induced by thioacetamide (TA) in rats was studied. Two months male rats,
      intraveously pretreated with a single dose of GD (0.1 mmol/Kg), were
      intraperitoneally injected with TA (6.6 mmol/Kg). Samples of blood and liver were
      obtained from rats at 0, 12, 24, 48, 72 and 96 h following TA intoxication.
      Parameters related to liver damage were determined in blood. In order to evaluate
      the mechanisms involved in the post-necrotic regenerative state, the levels of
      cyclin D and cyclin E as well as protein p27 and Proliferating Cell Nuclear
      Antigen (PCNA) were determined in liver extracts because of their roles in the
      control of cell cycle check-points. The results showed that GD significantly
      reduced the extent of necrosis. Noticeable changes were detected in the levels of
      cyclin D1, cyclin E, p27 and PCNA when compared to those induced by
      thioacetamide. Thus GD pre-treatment reduced TA-induced liver injury and
      accelerated the postnecrotic liver regeneration. These results demonstrate that
      Kupffer cells are involved in TA-induced liver and also in the postnecrotic
      proliferative liver states.

PMID- 21959303
TI  - Effect of EtOH/MgCl(2) molar ratios on the catalytic properties of MgCl(2)
      SiO(2)/TiCl(4) Ziegler-Natta catalyst for ethylene polymerization.
AB  - MgCl(2)-SiO(2)/TiCl(4) Ziegler-Natta catalysts for ethylene polymerization were
      prepared by impregnation of MgCl(2) on SiO(2) in heptane and further treatment
      with TiCl(4). MgCl(2).nEtOH adduct solutions were prepared with various
      EtOH/MgCl(2) molar ratios for preparation of the MgCl(2)-supported and MgCl(2)
      SiO(2)-supported catalysts in order to investigate the effect on polymerization
      performance of both catalyst systems. The catalytic activities for ethylene
      polymerization decreased markedly with increased molar ratios of [EtOH]/[MgCl(2)]
      for the MgCl(2)-supported catalysts, while for the bi-supported catalysts, the
      activities only decreased slightly. The MgCl(2)-SiO(2)-supported catalyst had
      relatively constant activity, independent of the [EtOH]/[MgCl(2)] ratio. The
      lower [EtOH]/[MgCl(2)] in MgCl(2)-supported catalyst exhibited better catalytic
      activity. However, for the MgCl(2)-SiO(2)-supported catalyst, MgCl(2) can
      agglomerate on the SiO(2) surface at low [EtOH]/[MgCl(2)] thus not being not
      suitable for TiCl(4) loading. It was found that the optimized [EtOH]/[MgCl(2)]
      value for preparation of bi-supported catalysts having high activity and good
      spherical morphology with little agglomerated MgCl(2) was 7. Morphological
      studies indicated that MgCl(2)-SiO(2)-supported catalysts have good morphology
      with spherical shapes that retain the morphology of SiO(2). The BET measurement
      revealed that pore size is the key parameter dictating polymerization activity.
      The TGA profiles of the bi-supported catalyst also confirmed that it was more
      stable than the mono-supported catalyst, especially in the ethanol removal
      region.

PMID- 21959304
TI  - Role of transgenic plants in agriculture and biopharming.
AB  - At present, environmental degradation and the consistently growing population are
      two main problems on the planet earth. Fulfilling the needs of this growing
      population is quite difficult from the limited arable land available on the
      globe. Although there are legal, social and political barriers to the utilization
      of biotechnology, advances in this field have substantially improved agriculture
      and human life to a great extent. One of the vital tools of biotechnology is
      genetic engineering (GE) which is used to modify plants, animals and
      microorganisms according to desired needs. In fact, genetic engineering
      facilitates the transfer of desired characteristics into other plants which is
      not possible through conventional plant breeding. A variety of crops have been
      engineered for enhanced resistance to a multitude of stresses such as herbicides,
      insecticides, viruses and a combination of biotic and abiotic stresses in
      different crops including rice, mustard, maize, potato, tomato, etc. Apart from
      the use of GE in agriculture, it is being extensively employed to modify the
      plants for enhanced production of vaccines, hormones, etc. Vaccines against
      certain diseases are certainly available in the market, but most of them are very
      costly. Developing countries cannot afford the disease control through such cost
      intensive vaccines. Alternatively, efforts are being made to produce edible
      vaccines which are cheap and have many advantages over the commercialized
      vaccines. Transgenic plants generated for this purpose are capable of expressing
      recombinant proteins including viral and bacterial antigens and antibodies.
      Common food plants like banana, tomato, rice, carrot, etc. have been used to
      produce vaccines against certain diseases like hepatitis B, cholera, HIV, etc.
      Thus, the up- and down-regulation of desired genes which are used for the
      modification of plants have a marked role in the improvement of genetic crops. In
      this review, we have comprehensively discussed the role of genetic engineering in
      generating transgenic lines/cultivars of different crops with improved nutrient
      quality, biofuel production, enhanced production of vaccines and antibodies,
      increased resistance against insects, herbicides, diseases and abiotic stresses
      as well as the safety measures for their commercialization.

PMID- 21959305
TI  - 2011 ACCF/AHA Focused Update of the Guideline for the Management of patients with
      peripheral artery disease (Updating the 2005 Guideline): a report of the American
      College of Cardiology Foundation/American Heart Association Task Force on
      practice guidelines.

PMID- 21959308
TI  - gamma-Synuclein is a promising new marker for staining reactive follicular
      dendritic cells, follicular dendritic cell sarcoma, Kaposi sarcoma, and benign
      and malignant vascular tumors.
AB  - Synucleins are small soluble proteins found in normal brain that facilitate rapid
      release of neurotransmitters. alpha-synuclein is a major component of the Lewy
      body of neurodegenerative diseases and gamma-synuclein is a marker of aggressive
      carcinomas. As the role of gamma-synuclein has not yet been investigated in the
      lymphoid system, we immunohistochemically stained normal lymphoid organs, lymph
      nodes with reactive lymphoid hyperplasia, and malignant lymphomas. The anti-gamma
      synuclein antibody strongly stained the follicular dendritic cell (FDC) meshworks
      and vascular and lymphatic endothelial cells in reactive lymphoid tissues, in B
      cell lymphomas with a nodular pattern, and in angioimmunoblastic T-cell
      lymphomas. There were no gamma-synuclein-positive FDC meshworks in B-cell or T
      cell lymphomas with a diffuse pattern. This is in contrast to CD21, which only
      stained the arms of the FDCs; gamma-synuclein highlighted both the long slender
      cellular processes and the cell body, thereby clearly demonstrating the number of
      individual FDCs. In addition, gamma-synuclein was strongly expressed by the
      neoplastic counterpart of reactive FDCs (FDC sarcoma) and by the neoplastic
      counterparts of normal lymphatic and vascular endothelial cells (Kaposi sarcoma,
      hemangioma, and angiosarcoma). Only a few spindle cell neoplasms (SSNs) derived
      from smooth muscle, peripheral nerve, or gastrointestinal stroma expressed gamma
      synuclein; however, gamma-synuclein was not expressed by 11 other types of SSNs
      tested. These results suggest that gamma-synuclein is a promising new adjunct
      marker for identifying reactive FDCs and for diagnosing FDC sarcoma and benign
      and malignant vascular tumors.

PMID- 21959309
TI  - Claudin-5 as an immunohistochemical marker for angiosarcoma and
      hemangioendotheliomas.
AB  - Claudin-5 is a tight junction protein expressed in endothelial cells and in some
      epithelial cells. It has been shown as a marker in canine angiosarcoma; however,
      data on human mesenchymal tumors are limited. In this study, we examined claudin
      5 in selected normal tissues, in 280 benign and malignant vascular tumors, and in
      448 other epithelial, mesenchymal, and neuroectodermal tumors. Early human
      embryos showed limited claudin-5 expression in endothelia of large truncal
      vessels, in liver sinusoids, and in the epidermis. In adult human tissues,
      claudin-5 was widely present in the endothelia of vessels of different calibers.
      However, neovascular capillaries in carcinomas and other tumors were often
      negative. Claudin-5 was also present in many glandular and ductal epithelia, hair
      shafts, and glomerular podocytes. Capillary and cavernous hemangiomas and
      lymphangiomas generally showed endothelial positivity; however, many vessels,
      especially those with poorly formed lumina, were negative in juvenile capillary
      hemangiomas, and fewer vessels were highlighted in lobular capillary hemangiomas.
      Hemangioendotheliomas of retiform, kaposiform, epithelioid, and epithelioid
      sarcoma-like types showed positivity, the latter in a diffuse cytoplasmic manner.
      Most angiosarcomas (115 of 119) and Kaposi sarcomas (28 of 29) showed strong
      labeling, but rare cases only contained positive cytoplasmic dots. Claudin-5 was
      commonly present in carcinomas (except in sarcomatoid ones), but most tumors
      showed heterogenous labeling weaker than that in angiosarcomas. Seminomas and
      renal cell, hepatocellular, and signet ring cell carcinomas were negative. Among
      non-vascular mesenchymal tumors, biphasic synovial sarcoma was the only tumor to
      contain claudin-5-positive nonvascular elements. In hemangiopericytomas, glomus
      tumor, and melanomas, claudin-5 was expressed in endothelial cells only. Claudin
      5 is a promising new marker for angiosarcomas and hemangioendotheliomas, but
      widespread expression in carcinomas and biphasic synovial sarcoma should be
      considered in the differential diagnosis and addressed with the use of an
      antibody panel including keratins, especially the more epithelial-specific
      AE1/AE3 and epithelial membrane antigen.

PMID- 21959310
TI  - The fake fat phenomenon in organizing pleuritis:  a source of confusion with
      desmoplastic malignant mesotheliomas.
AB  - We report 9 patients with pleural biopsies referred because of concern about
      infiltration of what appeared to be chest wall fat by pan-keratin-positive
      spindled cells, a finding that led to a consideration of desmoplastic
      mesothelioma. All patients showed pleural effusions/pleural thickening on
      computed tomographic scan. Pleural biopsy showed a greatly thickened and fibrotic
      paucicellular pleura with circular fat-like spaces and, sometimes, adjacent
      oblate spaces mostly deep in the fibrotic area. Indistinct, keratin-positive,
      spindle cells arranged parallel to the pleural surface coursed between these fat
      like spaces. S-100 stains were negative around the fat-like spaces. Vimentin
      stains showed that the spaces did not have a cellular lining of any kind.
      Sometimes the spaces contained faintly hematoxyphilic material that was Alcian
      blue positive, and similar material was seen in the fibrotic stroma. Follow-up
      with periods ranging from 6 to 30 months revealed that 8 cases had stable disease
      on chest imaging or by clinical findings. One case had slowly progressive pleural
      thickening. These observations suggest that spaces resembling fat may be
      encountered in fibrotic pleurae and that horizontally oriented keratin-positive
      spindled cells between the fat-like spaces deep in the fibrotic portion of a
      thickened pleura represent a benign finding seen in some cases of organizing
      pleuritis/fibrothorax. The spaces themselves are probably artifacts derived from
      the biopsy procedure and/or cutting artifacts. In contrast, in true desmoplastic
      mesotheliomas there is downward, rather than horizontal, growth of keratin
      positive spindled cells running between clearly definable fat cells.

PMID- 21959306
TI  - Curcumin nanoformulations: a future nanomedicine for cancer.
AB  - Curcumin, a natural diphenolic compound derived from turmeric Curcuma longa, has
      proven to be a modulator of intracellular signaling pathways that control cancer
      cell growth, inflammation, invasion and apoptosis, revealing its anticancer
      potential. In this review, we focus on the design and development of
      nanoparticles, self-assemblies, nanogels, liposomes and complex fabrication for
      sustained and efficient curcumin delivery. We also discuss the anticancer
      applications and clinical benefits of nanocurcumin formulations. Only a few novel
      multifunctional and composite nanosystem strategies offer simultaneous therapy as
      well as imaging characteristics. We also summarize the challenges to developing
      curcumin delivery platforms and up-to-date solutions for improving curcumin
      bioavailability and anticancer potential for therapy.

PMID- 21959311
TI  - Columnar-lined esophagus without intestinal metaplasia has no proven risk of
      adenocarcinoma.
AB  - Intestinal metaplasia in the columnar-lined esophagus (CLE) has long been
      recognized as the most significant histologic risk indicator for esophageal
      adenocarcinoma. Recent concern has been expressed, however, that
      nonintestinalized metaplastic columnar epithelia (cardiac epithelium in the
      esophagus) may also indicate risk. Of 2586 consecutive patients undergoing
      endoscopy and biopsy in the Foregut Surgery Department, we selected (a) 214
      patients with a visible CLE who had systemic 4-quadrant biopsies at 1 to 2 cm
      intervals, with the most proximal biopsy straddling the squamocolumnar junction,
      and (b) 109 patients without systematic biopsy who had dysplasia or
      adenocarcinoma. In the first group, 187 (87.4%) patients had intestinal
      metaplasia, and 27 (12.6%) had cardiac epithelium. Dysplasia or adenocarcinoma
      was present in 55 patients, all with intestinal metaplasia; its presence was
      significantly higher than in the cardiac epithelium group, none of whom had
      dysplasia or adenocarcinoma (P=0.01). In the second group with limited sampling,
      49 had only tumor tissue in the biopsy. Of 60 patients with nontumor epithelium,
      only 34 (56.7%) had residual intestinal metaplasia. We conclude that systematic
      biopsies of CLE as described in this study separate patients into those with and
      without intestinal metaplasia in such a manner as to remove the possibility of
      false-negative diagnosis of intestinal metaplasia. When intestinal metaplasia is
      absent using this biopsy protocol, the patient is at no or extremely low risk for
      dysplasia and cancer. When biopsies have a lower level of sampling of the segment
      of CLE, the absence of intestinal metaplasia cannot be interpreted as a true
      negative for intestinal metaplasia. Inadequate sampling is a powerful reason why
      the near absolute association between intestinal metaplasia and adenocarcinoma is
      not seen in some studies.

PMID- 21959312
TI  - Angiographic outcomes following stenting or coronary artery bypass surgery of the
      left main coronary artery: fifteen-month outcomes from the synergy between PCI
      with TAXUS express and cardiac surgery left main angiographic substudy (SYNTAX-LE
      MANS).
AB  - AIMS: The SYNTAX-LE MANS substudy prospectively evaluated 15-month angiographic
      and clinical outcomes in patients with treated left main (LM) disease. METHODS
      AND RESULTS: In the SYNTAX trial, 1,800 patients with three-vessel and/or LM
      disease were randomised to either CABG or PCI; of these, 271 LM patients were
      prospectively assigned to receive a 15-month angiogram. The primary endpoint for
      the CABG arm was the ratio of >=50% to <100% obstructed/occluded grafts bypassing
      LM lesions to the number placed. The primary endpoint for the PCI arm was the
      proportion of patients with <=50% diameter stenosis ('patent' stents) of treated
      LM lesions. Per protocol, no formal comparison between CABG and PCI arms was
      intended based on the differing primary endpoints. Available 15-month angiograms
      were analysed for 114 CABG and 149 PCI patients. At 15 months, 9.9% (26/263) of
      CABG grafts were 100% occluded and an additional 5.7% (15/263) were >=50% to
      <100% occluded. Overall, 27.2% (31/114) of patients had >=1 obstructed/occluded
      graft. The 15-month CABG MACCE rate was 8.8% (10/114) and MACCE at 15 months was
      not significantly associated with graft obstruction/occlusion (p=0.85). In the
      PCI arm, 92.4% (134/145) of patients had <=50% diameter LM stenosis at 15 months
      (89.7% [87/97] distal LM lesions and 97.9% [47/48] non-distal LM lesions). The 15
      month PCI MACCE rate was 12.8% (20/156) and this was significantly associated
      with lack of stent patency at 15 months (p<0.001), mainly due to repeat
      revascularisation. CONCLUSIONS: At 15 months, 15.6% (41/263) of grafts were at
      least 50% obstructed but this was not significantly associated with MACCE; 92.4%
      (134/145) of patients had stents that remained patent at 15 months, and stent
      restenosis was significantly associated with MACCE, predominantly due to
      revascularisation.

PMID- 21959313
TI  - Modeling oxygen transport in human placental terminal villi.
AB  - Oxygen transport from maternal blood to fetal blood is a primary function of the
      placenta. Quantifying the effectiveness of this exchange remains key in
      identifying healthy placentas because of the great variability in capillary
      number, caliber and position within the villus-even in placentas deemed
      clinically "normal". By considering villous membrane to capillary membrane
      transport, stationary oxygen diffusion can be numerically solved in terminal
      villi represented by digital photomicrographs. We aim to provide a method to
      determine whether and if so to what extent diffusional screening may operate in
      placental villi. Segmented digital photomicrographs of terminal villi from the
      Pregnancy, Infection and Nutrition study in North Carolina 2002 are used as a
      geometric basis for solving the stationary diffusion equation. Constant maternal
      villous oxygen concentration and perfect fetal capillary membrane absorption are
      assumed. System efficiency is defined as the ratio of oxygen flux into a villus
      and the sum of the capillary areas contained within. Diffusion screening is
      quantified by comparing numerical and theoretical maximum oxygen fluxes. A strong
      link between various measures of villous oxygen transport efficiency and the
      number of capillaries within a villus is established. The strength of diffusional
      screening is also related to the number of capillaries within a villus. Our
      measures of diffusional efficiency are shown to decrease as a function of the
      number of capillaries per villus. This low efficiency, high capillary number
      relationship supports our hypothesis that diffusional screening is present in
      this system. Oxygen transport per capillary is reduced when multiple capillaries
      compete for diffusing oxygen. A complete picture of oxygen fluxes, capillary and
      villus areas is obtainable and presents an opportunity for future work.

PMID- 21959315
TI  - A model-experiment comparison of system dynamics for human walking and running.
AB  - The human musculo-skeletal system comprises high complexity which makes it
      difficult to identify underlying basic principles of bipedal locomotion. To
      tackle this challenge, a common approach is to strip away complexity and
      formulate a reductive model. With utter simplicity a bipedal spring-mass model
      gives good predictions of the human gait dynamics, however, it has not been fully
      investigated whether center of mass motion over time of walking and running is
      comparable between the model and the human body over a wide range of speed. To
      test the model's ability in this respect, we compare sagittal center of mass
      trajectories of model and human data for speeds ranging from 0.5 m/s to 4 m/s.
      For simulations, system parameters and initial conditions are extracted from
      experimental observations of 28 subjects. The leg parameters stiffness and length
      are extracted from functional fitting to the subjects' leg force-length curves.
      With small variations of the touch-down angle of the leg and the vertical
      position of the center of mass at apex, we find successful spring-mass
      simulations for moderate walking and medium running speeds. Predictions of the
      sagittal center of mass trajectories and ground reaction forces are good, but
      their amplitudes are overestimated, while contact time is underestimated. At
      faster walking speeds and slower running speeds we do not find successful model
      locomotion with the extent of allowed parameter variation. We conclude that the
      existing limitations may be improved by adding complexity to the model.

PMID- 21959314
TI  - Quantification of gastrointestinal sodium channelopathy.
AB  - Na(v)1.5 sodium channels, encoded by SCN5A, have been identified in human
      gastrointestinal interstitial cells of Cajal (ICC) and smooth muscle cells (SMC).
      A recent study found a novel, rare missense R76C mutation of the sodium channel
      interacting protein telethonin in a patient with primary intestinal pseudo
      obstruction. The presence of a mutation in a patient with a motility disorder,
      however, does not automatically imply a cause-effect relationship between the
      two. Patch clamp experiments on HEK-293 cells previously established that the
      R76C mutation altered Na(v)1.5 channel function. Here the process through which
      these data were quantified to create stationary Markov state models of wild-type
      and R76C channel function is described. The resulting channel descriptions were
      included in whole cell ICC and SMC computational models and simulations were
      performed to assess the cellular effects of the R76C mutation. The simulated ICC
      slow wave was decreased in duration and the resting membrane potential in the SMC
      was depolarized. Thus, the R76C mutation was sufficient to alter ICC and SMC cell
      electrophysiology. However, the cause-effect relationship between R76C and
      intestinal pseudo-obstruction remains an open question.

PMID- 21959316
TI  - The potential role of the X chromosome in the emergence of male-killing from
      mutualistic endosymbionts.
AB  - Endosymbionts infect most arthropods and cause a wide variety of phenotypes in
      their hosts, ranging from obligate mutualists to reproductive parasites. One of
      the most dramatic forms of reproductive parasitism is male-killing which involves
      the endosymbiont killing all of the sons of infected females. A phenotype with
      such a dramatic effect on host fitness is expected to provide strong selection
      for suppressors of male-killing, yet in many well-studied male-killer/arthropod
      systems, no suppressors have been found. Plausible explanations for a lack of
      resistance exist and include cryptic cytoplasmic incompatibility (males that
      survive male-killing are therefore infected and matings with uninfected females
      are incompatible) and deleterious pleiotropic effects of altering early embryonic
      development--the precise time when male-killing often occurs. Here I describe
      another possible scenario that sidesteps the problem: male killing may arise
      through an epistatic interaction between an endosymbiont and a paternally acting
      locus on the X chromosome. Since paternal X chromosomes never find themselves in
      sons, they never suffer from male-killing and instead enjoy any benefits
      (decreased sibling competition, inbreeding avoidance) caused by killing males.
      This scenario allows for the possibility that male-killing arose recently, even
      if there is no evidence for evolution in the endosymbiont genotype.

PMID- 21959317
TI  - Simulation of action potential propagation in plants.
AB  - Action potential is considered to be one of the primary responses of a plant to
      action of various environmental factors. Understanding plant action potential
      propagation mechanisms requires experimental investigation and simulation;
      however, a detailed mathematical model of plant electrical signal transmission is
      absent. Here, the mathematical model of action potential propagation in plants
      has been worked out. The model is a two-dimensional system of excitable cells;
      each of them is electrically coupled with four neighboring ones. Ion diffusion
      between excitable cell apoplast areas is also taken into account. The action
      potential generation in a single cell has been described on the basis of our
      previous model. The model simulates active and passive signal transmission well
      enough. It has been used to analyze theoretically the influence of cell to cell
      electrical conductivity and H(+)-ATPase activity on the signal transmission in
      plants. An increase in cell to cell electrical conductivity has been shown to
      stimulate an increase in the length constant, the action potential propagation
      velocity and the temperature threshold, while the membrane potential threshold
      being weakly changed. The growth of H(+)-ATPase activity has been found to induce
      the increase of temperature and membrane potential thresholds and the reduction
      of the length constant and the action potential propagation velocity.

PMID- 21959318
TI  - Gender and science in Hiroshima's aftermath: a cross-cultural approach.
AB  - A comparative study of Japanese and Japanese-American survivors of the atomic
      bombs dropped on Hiroshima and Nagasaki in 1945 suggests that there is much to be
      gained by looking at the history of the Bomb as a cross-cultural history. Issues
      of science and gender in survivors' experiences and memories illuminate three key
      features of the trans-Pacific history: a Japanese female author's literary
      responses to the Bomb, the Japan-U.S. relationship after the war that shaped
      Japan's antinuclear movement, and Japanese-American survivors' effort to gain
      governmental recognition and medical care in the U.S. within the context of the
      Asian American movement. Using variety of sources--literature, popular political
      discourse, congressional hearings, and oral histories--this article shows the
      volatile diffusion of political and cultural ideas revealed by a trans-Pacific
      perspective.

PMID- 21959319
TI  - Semiconducting polymer thin films by surface-confined stepwise click
      polymerization.
AB  - Surface-confined stepwise click polymerization was used to prepare surface
      attached thin films of semiconducting polymers. These highly uniform films showed
      extended UV/vis absorption characteristics and a remarkable degree of molecular
      organization with a unidirectional alignment of the polymer chains normal to the
      surface.

PMID- 21959320
TI  - Four-year clinical follow-up of the ABSORB everolimus-eluting bioresorbable
      vascular scaffold in patients with de novo coronary artery disease: the ABSORB
      trial.
AB  - AIM: The first-in-man ABSORB Cohort A trial demonstrated the bioresorption of the
      ABSORB BVS (Abbott Vascular, Santa Clara, CA, USA) at two years. This report
      describes the 4-year clinical outcomes. METHODS AND RESULTS: The ABSORB Cohort A
      trial enrolled 30 patients with a single de novo native coronary artery lesion.
      Clinical follow-up was available in 29 patients since one patient withdrew
      consent after the six month follow-up. At four years, the hierarchical ID-MACE of
      3.4% remained unchanged. Clopidogrel therapy had been discontinued in all
      patients. CONCLUSION: Four-year clinical results demonstrate a sustained low MACE
      rate (3.4%) without any late complications such as stent thrombosis.

PMID- 21959321
TI  - The missing link: implementation of morphogenetic growth control on the cellular
      and molecular level.
AB  - In the wing imaginal disc of Drosophila melanogaster, the morphogen Dpp controls
      growth, probably in an instructive manner. Many models for growth control by Dpp
      have been proposed and have been extensively discussed elsewhere. In this review,
      we speculate on how instructive growth control could provide a link between Dpp
      signaling and cell growth and/or cell cycle progression and so implement
      morphogenetic growth control on the cellular and molecular levels.

PMID- 21959322
TI  - Gastric emptying scintigraphy: is four hours necessary?
AB  - INTRODUCTION: Recommendations for gastric emptying scintigraphy (GES) suggest
      imaging over 4 hours to better define gastroparesis. AIMS: To determine the value
      of defining delayed gastric emptying at time points earlier than 4 hours.
      METHODS: GES was performed with ingestion of a liquid egg white meal with imaging
      at 0, 0.5, 1, 2, 3, and 4 hours. Patients completed the Patient Assessment of
      Gastrointestinal Symptoms questionnaire immediately before GES. RESULTS: Of 1499
      patients undergoing GES from September 2007 to January 2010 (76.2% were female,
      mean age of 45.5+/-0.5 y, 21.3% had diabetes, 9.5% had earlier gastric surgery),
      160 (10.7%) had increased gastric retention at 1 hour (>90%), 404 (27%) had
      increased retention at 2 hours (>60%), 576 (38.4%) had increased retention at 3
      hours (>30%), and 629 (42%) had increased retention at 4 hours (>10%). Gastric
      retention at 4 hours correlated with retention at 3 hours (r=0.890; P<0.001), 2
      hours (r=0.738; P<0.001), and 1 hour (r=0.510; P<0.001). Symptoms correlated
      better with the gastric retention at later time points. The symptoms correlating
      with gastric retention at 4 hours included early satiety (r=0.170; P<0.01),
      vomiting (r=0.143; P<0.01), feeling excessively full after meals (r=0.123;
      P<0.01), and loss of appetite (r=0.122; P<0.01). CONCLUSIONS: Gastric retention
      at 4 hours correlates well with gastric retention at 3 hours, good at 2 hours,
      but only fair with gastric retention at 1 hour. Gastric retention at 1 hour may
      miss 36% of patients found to have delayed gastric emptying at 4 hours. Symptoms
      (early satiety, vomiting, feeling excessively full after meals, and loss of
      appetite) correlated better with the gastric retention at later time points.

PMID- 21959323
TI  - 24 Versus 48-hour bravo pH monitoring.
AB  - BACKGROUND: Historical ambulatory pH monitoring systems for the evaluation of
      gastroesophageal reflux disease have been catheter based and uncomfortable for
      patients, commonly limiting both their diet and activities. Catheter-based
      studies have also been reported to underestimate the amount of reflux a patient
      may have in a normal, routine day. Compared with conventional catheter-based pH
      monitoring systems, wireless (Bravo) pH monitoring is better tolerated by
      patients and allows for an increased duration of pH recording. Currently, there
      is lack of data regarding the optimal duration of wireless studies and concern
      that day 1 results are not typical of a patient's routine lifestyle, given the
      effects of sedation. Few studies have evaluated the merits of 24 versus 48-hour
      wireless pH monitoring. AIMS: The aims of this study were (1) to identify
      differences in reflux parameters between 24 versus 48-hour testing as measured by
      wireless pH monitoring and (2) to assess the effect of 48-hour studies on the
      number of reflux episodes and symptom correlation as compared with 24-hour
      studies. METHODS: A retrospective chart review of 124 consecutive patients who
      underwent 48-hour wireless esophageal pH monitoring studies was prepared. All
      patients underwent esophagogastroduodenoscopy using intravenous conscious
      sedation before wireless capsule placement. Acid reflux variables (including
      total reflux time, number of reflux episodes, and total percent time of pH<4) and
      symptom-association probability (SAP) scores were compared for day 1 versus day 2
      versus total. RESULTS: Forty-eight-hour SAP scores were significantly higher when
      compared with the first 24 hours for all reported primary symptoms. SAP scores
      were calculated at 24 and 48 hours, respectively for heartburn (56 vs. 65,
      P<0.0001), regurgitation (65 vs. 80, P<0.0001), chest pain (59 vs. 78, P=0.0009),
      and cough (55 vs. 64, P=0.0027). In addition, the percentage of SAP scores >95
      was significantly higher for both heartburn and regurgitation (34% vs. 48%,
      P=0.003 and 38% vs. 62%, P=0.005). As expected, 48-hour testing also captured a
      significantly higher number of reflux episodes as compared with day 1 results
      alone (97 vs. 47, P<0.0001). There were no statistical differences noted between
      the 2 days for total percent time of pH <4. CONCLUSIONS: Forty-eight-hour
      wireless (Bravo) pH monitoring strengthens symptom correlation as compared with
      24-hour results alone and yields a greater percentage of SAP scores >95 for
      typical symptoms of gastroesophageal reflux disease. Prolonged recording of
      patient symptoms and/or sedation effects may account for the better symptom
      correlation. Although there were no statistical differences seen in this study
      between 24 and 48-hour studies for total percent time pH <4, 48-hour studies
      captured significantly more reflux episodes as compared with 24 hours of
      monitoring alone. These results suggest that patients undergoing wireless pH
      monitoring should have 48-hour studies performed as a standard of practice.

PMID- 21959324
TI  - Do gastroenterologists adhere to diagnostic and treatment guidelines for celiac
      disease?
AB  - AIM: Our group hypothesized that significant variation exists between suggested
      clinical guidelines, the clinical practices of practicing gastroenterologists and
      academic experts in celiac disease (CD). METHOD: We designed 4 CD vignettes
      comparing experts and practicing gastroenterologists. Practicing
      gastroenterologists (n=169) were surveyed during Digestive Disease Week 2009 and
      experts (n=22) answered e-mail surveys. Ratings for answers in each vignette was
      done using a 9-point RAND Appropriateness Scale (RAS) with endorsement defined as
      RAS score of 7 to 9. We also calculated the RAND "Disagreement Index" (DI) was
      calculated, with DI>1.0 indicated extreme variation. RESULTS: A total of 169
      practicing gastroenterologists and 22 experts were included. Differences in all
      vignette answers were present. Differences were seen for use of IgA anti
      endomysial antibodies (P=0.0241), human leukocyte antigen DQ2/8 testing
      (P=0.0325), gluten challenge (P<0.0001), and oat consumption (P<0.0001). There
      were differences in recommendations for biopsy review (P=0.0479) and management
      of dermatitis herpetiformis (P=0.0025). Experts consistently endorsed CD
      screening in patients with type 1 diabetes, Down and Turner syndromes, and
      relatives of CD patients compared with practicing physicians (P=0.0054, 0.0003,
      <0.0001, 0.0304). Experts endorsed CD screening for atypical presentations
      (delayed puberty, elevated transaminases, primary biliary cirrhosis, autoimmune
      hepatitis, and infertility). CONCLUSION: There is significant disagreement
      between nonexperts and experts in diagnosis and management of CD. Promotion of
      existing guidelines and further research is advised.

PMID- 21959325
TI  - Endoscopic submucosal dissection is an effective and safe therapy for early
      gastric neoplasms: a multicenter feasible study.
AB  - BACKGROUND AND AIM: The technique of endoscopic submucosal dissection (ESD) was
      introduced to obtain en bloc specimens of large early gastrointestinal neoplasms.
      The drawback of ESD is its technical difficulty and, consequently, its higher
      rate of complication. In this multicenter study, we investigated the therapeutic
      outcomes of ESD in consecutive patients. METHODS: From January 2002 to December
      2008, 485 early gastric neoplasms in 418 patients were consecutively treated by
      using ESD procedure performed by 6 endoscopists in 4 institutions in Tokyo.
      Demorgraphics, tumor location, therapeutic outcomes, and complication rates were
      analyzed. RESULTS: The rates of en bloc resection, complete en bloc resection,
      submucosal invasion, and piecemeal resection were 93.6%, 85.4%, 10.9%, and 5.4%,
      respectively. In multivariate analysis, the en bloc resection rate was
      independently lower in lesions in upper portion than in lower portion (P<0.01),
      lower in larger lesions (>30 mm, P<0.05; 20 to 30 mm, P<0.05), and lower in
      lesions with a scar (P<0.01). Delayed bleeding occurrence was independently high
      in larger lesions (>30 mm, P<0.01; 20 to 29 mm, P<0.01) than in small lesions
      (<20 mm). Institution and endoscopists were not risk factors of en bloc resection
      and complications CONCLUSIONS: ESD is an effective and safe therapy in the
      management of early gastric neoplasms when performed by well-trained
      endoscopists. Endoscopists should recognize the difficulty to perform ESD for en
      bloc resection of upper lesion, and the risk of delayed bleeding in cases of
      lesions >2 cm in size.

PMID- 21959326
TI  - Safe landing for global polio eradication: a perspective.
AB  - After over two decades of immense efforts, the global polio eradication
      initiative may be approaching its final phase. With leadership from WHO, great
      efforts of national programs and support from its collaborators, combined with
      the recent use of mono and bivalent oral polio vaccines, success may be at hand.
      For a "safe landing" of this global program, it is important once more to recall
      the key role of routine vaccination as the foundation on which mass vaccination
      campaigns can be successful. Continued effective routine vaccination programs are
      essential to reduce the ill effects of high population density in formerly
      endemic countries. Considering the large number of subclinical poliovirus
      infections, failing to reduce the number of unvaccinated persons per km(2) could
      severely impact the final stage of eradication. Here the authors, from their
      personal perspectives, discuss how the current program will be viewed from 2012
      onwards. The authors will highlight the epidemiological importance of circulating
      vaccine-derived poliovirus, the problem of biosecurity as well as the use of
      inactivated polio vaccine and how each of these may affect the post eradication
      era and how research into each of these must continue to ensure success.

PMID- 21959327
TI  - Attenuation of bovine herpesvirus type 1 by deletion of its glycoprotein G and tk
      genes and protection against virulent viral challenge.
AB  - To develop a novel vaccine against infectious bovine rhinotracheitis (IBR), a
      bovine herpesvirus-1 (BoHV-1) mutant was constructed by deleting the genes for
      glycoprotein G (gG) and thymidine kinase (tk) through homologous recombination.
      The resulting sequences for both genes were shown to be correct and a gG
      expression defect was also confirmed. A parallel study of the BoHV-1 gG(-)/tk(-),
      gE(-)/tk(-) mutants and wild type (wt) in 31 calves was performed at three
      different doses, 4*10(5)PFU, 4*10(6)PFU and 4*10(7)PFU. Compared to wt BoHV-1,
      inoculation of BoHV-1 gG(-)/tk(-) and gE(-)/tk(-) produced no clinical signs and
      the virus was not reactivated by dexamethasone (dex). Inoculation of BoHV-1 gG(
      )/tk(-) at the doses of 4*10(6) and 4*10(7)PFU provided full clinical protection
      for the cattle against wt BoHV-1 challenge at 4*10(7)PFU/calf. Although the
      mutants were associated with significantly lower levels of serum neutralizing
      antibody, interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF
      alpha) than wt BoHV-1 on days 3, 5 and 7 after immunization, stimulation of IFN
      beta by BoHV-1 gG(-)/tk(-) was significantly higher than that of wt BoHV-1 and
      gE(-)/tk(-) on days 3 and 5. We conclude that BoHV-1 gG(-)/tk(-) was attenuated
      adequately and that it maintains the ability to stimulate immune protection.
      Therefore, it may be a promising candidate for a marker vaccine against IBR.

PMID- 21959328
TI  - Influenza associated mortality in the subtropics and tropics: results from three
      Asian cities.
AB  - Influenza has been well documented to significantly contribute to winter increase
      of mortality in the temperate countries, but its severity in the subtropics and
      tropics was not recognized until recently and geographical variations of disease
      burden in these regions remain poorly understood. In this study, we applied a
      standardized modeling strategy to the mortality and virology data from three
      Asian cities: subtropical Guangzhou and Hong Kong, and tropical Singapore, to
      estimate the disease burden of influenza in these cities. We found that influenza
      was associated with 10.6, 13.4 and 8.3 deaths per 100,000 population in
      Guangzhou, Hong Kong and Singapore, respectively. The annual rates of excess
      deaths in the elders were estimated highest in Guangzhou and lowest in Singapore.
      The excess death rate attributable to A/H1N1 subtype was found slightly higher
      than the rates attributable to A/H3N2 during the study period of 2004-2006 based
      on the data from Hong Kong and Guangzhou. Our study revealed a geographical
      variation in the disease burden of influenza in these subtropical and tropical
      cities. These results highlight a need to explore the determinants for severity
      of seasonal influenza.

PMID- 21959329
TI  - Induction of Bordetella pertussis-specific immune memory by DTPa vaccines.

PMID- 21959330
TI  - CD40L-null NKT cells provide B cell help for specific antibody responses.
AB  - CD1d-binding glycolipids exert potent adjuvant effects on T-dependent Ab
      responses. The mechanisms include cognate interaction between CD1d-expressing B
      cells and TCR-expressing Type I CD1d-restricted natural killer T cells (NKTs).
      However, the critical NKT-derived factors that stimulate B cells are poorly
      understood. We tested the hypothesis that CD1d-driven CD40L expression by NKT
      cells influences humoral immunity. Bone marrow chimeras with CD40L(+/+) or CD40L(
      /-) NKT cells were immunized with Ag plus CD1d ligand before measuring Ab
      responses. CD40L(-/-) NKT cells stimulated higher endpoint Ab titers than
      controls expressing CD40L. In contrast, immunization of CD40L(-/-) mice revealed
      that CD40L(-/-) NKT cells could not provide B cell help when Th cells lacked
      CD40L. We report that CD40L(-/-) NKT cells can provide help for Ab production and
      do so cooperatively with CD40L(+/+) Th cells. We suggest that the manner in which
      NKT cells provide B cell help is distinct from that of Th cells.

PMID- 21959331
TI  - The antitumor immunopreventive effects of a DNA vaccine against CYP26a1 on mouse
      breast carcinoma.
AB  - BACKGROUND: CYP26a1, which functioned mainly as a retinoic acid (RA) catabolic
      enzyme, has been shown to be oncogenic and to support cell survival in many
      breast carcinoma cells. OBJECTIVES: The purpose of the study was to investigate
      the antitumor effect of a DNA vaccine targeting CYP26a1 on breast tumors
      development in mice which highly express CYP26a1 and to further clarify its
      potential mechanism. METHODS: After three times immunization of the DNA vaccine,
      the BALB/c mice were inoculated with the engineered 4T1 breast cancer cells
      expressing CYP26a1. Primary tumors were measured every 4 days after tumor cell
      inoculation. The primary tumors were surgically removed and weighted after 30
      days of inoculation. The anti-CYP26a1 antibody titer of the antiserum was
      measured by an enzyme-linked immunosorbent assay (ELISA). The effect of the
      vaccine on apoptosis of the primary tumor was determined by terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). Apoptosis
      related proteins in primary tumor were detected by Western blotting. The
      expression of the Th1 and Th2 type cytokines was detected by RT-PCR. RESULTS: The
      vaccine could elicit the production of anti-CYP26a1 antibody and significantly
      inhibit the growth of the primary tumor compared to the control groups (p<0.05).
      The vaccine induced the apoptosis of the primary tumor with the increase in
      expression of apoptosis-related proteins p53, Caspase3 and Fas. Furthermore, the
      vaccine increased the expression of the Th1 cytokine, but not the expression of
      Th2 cytokine. CONCLUSION: Our study shows that the vaccine targeting CYP26a1
      significantly inhibits the primary tumor growth and progression by activating the
      apoptosis pathway and by eliciting both humoral and cellular immune responses.

PMID- 21959332
TI  - An epidemiological study of the serum thyrotropin reference range and factors
      that influence serum thyrotropin levels in iodine sufficient areas of China.
AB  - The aims of this study performed in 2007 were to verify the selection criteria
      proposed by the National Academy of Clinical Biochemistry (NACB) guidelines, to
      investigate factors that influence thyrotropin (TSH) levels, and to determine
      serum TSH reference range in iodine sufficient areas of China. After excluding
      291 subjects, a total of 5,348 inhabitants from three iodine sufficient areas of
      Liaoning province were asked to fulfill the questionnaire, and take TSH, thyroid
      peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) measurements and a
      thyroid ultrasound examination. The distribution of TSH was right skewed in
      normal people. It has been customary to log transform the values to observe the
      Gaussian distribution. In the subjects 12-19 years of age, the TSH level was
      significantly higher than in the other age groups (p<0.001), while there were no
      significant difference in the TSH values of the other age groups. The TSH levels
      in females(1.68+/-1.90mIU/L) were significantly higher than in males (1.45+/
      1.92mIU/L) (p<0.001). Therefore, the normal TSH range in males over age 20 was
      0.43-4.74mIU/L, and in females the range was 0.48-5.39 mIU/L. A family history of
      thyroid disease, abnormal thyroid ultrasound, a thyroid antibody-positive status
      were the factors that influenced the TSH reference range. Non-thyroid disease did
      not impact the TSH reference range significantly. We recommend use of a TSH
      reference range 0.46-5.19mIU/L in iodine sufficient areas of China for males and
      females over 20 years old. We suggest using a normal thyroid ultrasound as a new
      criterion in addition to the NACB guidelines to determine the TSH reference
      range.

PMID- 21959333
TI  - Association between accumulation of visceral fat and the combination of beta3
      adrenergic receptor Trp64Arg, beta2 adrenergic receptor Arg16Gly and uncoupling
      protein 1 -3826A>G polymorphisms detected by Smart Amplification Process 2.
AB  - beta2 and beta3 adrenergic receptors (beta2AR, beta3AR) and uncoupling protein 1
      (UCP1) have been considered as candidate genes for obesity.  Although each
      polymorphism of beta3AR Trp64Arg, beta2AR Arg16Gly and UCP1 -3826A>G is known to
      be associated with obesity, the interaction among these polymorphisms is not
      fully understood.  We analyzed beta3AR Trp64Arg, beta2AR Arg16Gly and UCP1 
      3826A>G polymorphisms by the Smart Amplification Process 2 in 222 Japanese
      subjects without the medication of hypertension, dyslipidemia or diabetes, and
      investigated the association between the physical and metabolic characteristics
      and the combination of these polymorphisms.  In analysis of the genotypes
      combination, only the carriers of both beta2AR Arg/Arg and UCP1 G/G genotypes had
      significantly higher waist to hip ratio (p=0.014).  In analysis of the alleles
      combination, a significant difference was observed in waist to hip ratio among
      the groups stratified by the carrying number of the alleles of beta3AR Arg,
      beta2AR Arg and UCP1 G (p=0.026), and the waist to hip ratio was significantly
      higher in the carriers of four and five risk alleles than in the carriers from
      zero to three risk alleles (p=0.005).  The present study demonstrated the
      interaction among beta3AR Trp64Arg, beta2AR Arg16Gly and UCP1 -3826A>G for the
      accumulation of visceral fat.

PMID- 21959334
TI  - The prevalence and treatment gap of epilepsy in Tbilisi, Georgia.
AB  - INTRODUCTION: Data on the prevalence of epilepsy and the extent of its treatment
      gap are important for planning health care delivery for people with epilepsy. The
      prevalence of active epilepsy in Georgia prior to the social and political re
      organization in the early 1990s was estimated at around 5.7 per 1000. Changes to
      the social structure of the country may have affected this. There is no previous
      estimate of the treatment gap. METHODS: A door-to-door survey was carried out
      using a validated screening questionnaire to determine the prevalence of epilepsy
      and the extent of the treatment gap amongst a population of about 10,000 people
      in Tbilisi, the capital of Georgia. The diagnosis of epilepsy amongst those who
      screened positive was confirmed by a multidisciplinary team. RESULTS: Lifetime
      prevalence was 11.4/1000. The prevalence of active epilepsy was estimated at
      8.8/1000, and 5/1000 had seizures in the previous 12 months. About two thirds of
      people with active epilepsy had not received appropriate antiepileptic treatment
      in the month prior to the survey. 89% had focal epilepsy and two thirds had co
      morbidity (neurological deficits, behavioral, psychiatric or somatic problems).
      CONCLUSION: The prevalence of epilepsy was higher than previously estimated and
      the treatment gap was substantial. Results should inform the planning of epilepsy
      care delivery in the country.

PMID- 21959336
TI  - Micellar system in copper-catalysed hydroxylation of arylboronic acids: facile
      access to phenols.
AB  - Copper-catalysed oxidative hydroxylation of arylboronic acids was accomplished in
      water containing an amphiphilic surfactant, providing facile access to phenol
      derivatives.

PMID- 21959335
TI  - High incidence of pediatric idiopathic epilepsy is associated with familial and
      autosomal dominant disease in Eastern Newfoundland.
AB  - PURPOSE: To describe the incidence and epidemiology of pediatric idiopathic
      epilepsy (IE) in Newfoundland and Labrador. METHODS: All children in Newfoundland
      and Labrador aged 0-15 years with IE were ascertained through the provincial
      neurology clinic at the Janeway Child Health Centre. Family history, medical
      history and blood samples were obtained from probands and relatives. Two genes,
      SCN1A and KCNQ2, were screened for mutations by direct sequencing. RESULTS: The
      mean annual incidence of IE for the population of children living in the Avalon
      region of Newfoundland from 2000 to 2004 was 107 per 100,000. This rate is
      approximately three-fold greater than rates reported in other developed
      countries. Of 117 families with IE eligible for study, 86 (74%) provided detailed
      pedigree data. Multiple different epilepsy phenotypes were identified. Fifty-five
      families (64%) had a positive family history. Eight of these had family histories
      compatible with autosomal dominant (AD) inheritance and these families lived in
      five different geographic isolates. DNA was obtained from 21 families (79
      individuals). The two previously identified mutations in Newfoundland families
      with epilepsy were sequenced and excluded as pathogenic sites in all but one
      family which had a mutation in SCN1A. CONCLUSION: The incidence of IE is high in
      the Avalon Peninsula of Newfoundland and the rate of familial disease is high
      throughout the province of Newfoundland and Labrador. The distribution of
      familial and AD IE in different geographic isolates, together with the clinical
      heterogeneity of disease suggests substantial genetic heterogeneity. It is likely
      that other novel mutations will be identified in this population.

PMID- 21959337
TI  - The effect of decreasing computed tomography dosage on radiostereometric analysis
      (RSA) accuracy at the glenohumeral joint.
AB  - Standard, beaded radiostereometric analysis (RSA) and markerless RSA often use
      computed tomography (CT) scans to create three-dimensional (3D) bone models.
      However, ethical concerns exist due to risks associated with CT radiation
      exposure. Therefore, the aim of this study was to investigate the effect of
      decreasing CT dosage on RSA accuracy. Four cadaveric shoulder specimens were
      scanned using a normal-dose CT protocol and two low-dose protocols, where the
      dosage was decreased by 89% and 98%. 3D computer models of the humerus and
      scapula were created using each CT protocol. Bi-planar fluoroscopy was used to
      image five different static glenohumeral positions and two dynamic glenohumeral
      movements, of which a total of five static and four dynamic poses were selected
      for analysis. For standard RSA, negligible differences were found in bead (0.21+/
      0.31mm) and bony landmark (2.31+/-1.90mm) locations when the CT dosage was
      decreased by 98% (p-values>0.167). For markerless RSA kinematic results,
      excellent agreement was found between the normal-dose and lowest-dose protocol,
      with all Spearman rank correlation coefficients greater than 0.95. Average root
      mean squared errors of 1.04+/-0.68mm and 2.42+/-0.81 degrees  were also found at
      this reduced dosage for static positions. In summary, CT dosage can be markedly
      reduced when performing shoulder RSA to minimize the risks of radiation exposure.
      Standard RSA accuracy was negligibly affected by the 98% CT dose reduction and
      for markerless RSA, the benefits of decreasing CT dosage to the subject outweigh
      the introduced errors.

PMID- 21959339
TI  - Current and future avoidable cost of smoking--estimates for Sweden 2007.
AB  - OBJECTIVE: To estimate current and future avoidable smoking-attributable costs in
      Sweden for the year 2007. DESIGN: Disease specific smoking-attributable
      proportions were calculated for Swedish smoking patterns and applied to estimate
      costs for smoking-related diseases based on data from public registers. Avoidable
      future effects of smoking were calculated employing a Markov simulation model.
      RESULTS: The estimated total cost in 2007 was USD 1.6 billion, or USD 181 per
      capita. Healthcare (direct) cost accounted for 30% of the total cost. The number
      of deaths was 97 per 100,000 inhabitants (79 in 2001); the number of years of
      potential life lost 1,227 per 100,000 inhabitants (1012 in 2001); and the number
      of years of potential productive life lost 226 (185 in 2001) per 100,000
      inhabitants. Avoidable future lifetime costs, per 100,000 inhabitants, amounted
      to USD 19 million (healthcare), 14,000 years of potential life lost,
      corresponding to a present value of USD 158 million. Total avoidable cost of
      current smoking amounted to USD 16 billion. CONCLUSION: In spite of declining
      smoking-prevalence rates during the last 30 years, smoking-attributable deaths
      increased between 2001 and 2007. The number of life years lost per death
      decreased somewhat, indicating that the age distribution of those dying shifted
      further towards older age. Simulations indicate that smoking-cessation among
      young smokers yields considerable more benefits each year than smoking-cessation
      among older smokers. The health benefits that accrued in 2007, as a result of
      declining smoking prevalence since 1980, correspond to more than the total cost
      of smoking in that year.

PMID- 21959340
TI  - Night blindness in a teenager with cystic fibrosis.
AB  - This article describes the case of a 16-year-old boy with cystic fibrosis who
      presented with difficulty seeing in the dark. He had a history of bowel surgery
      at birth, and he developed cystic fibrosis liver disease and osteopenia during
      his teenage years. He always had good lung function. When his serum vitamin A
      level was checked, it was undetectable in sample. He was diagnosed with night
      blindness and commenced on high-dose vitamin A. His symptoms resolved within 3
      days. However, it took over 1 year for his vitamin A level to return to normal.
      This case emphasizes the importance of monitoring vitamin levels in cystic
      fibrosis to detect deficiency and prevent long-term consequences, and it
      highlights the challenges encountered during the course of night blindness
      treatment.

PMID- 21959341
TI  - Glutathione depletion prevents diet-induced obesity and enhances insulin
      sensitivity.
AB  - Excessive accumulation of reactive oxygen species (ROS) in adipose tissue has
      been implicated in the development of insulin resistance and type 2 diabetes.
      However, emerging evidence suggests a physiologic role of ROS in cellular
      signaling and insulin sensitivity. In this study, we demonstrate that
      pharmacologic depletion of the antioxidant glutathione in mice prevents diet
      induced obesity, increases energy expenditure and locomotor activity, and
      enhances insulin sensitivity. These observations support a beneficial role of ROS
      in glucose homeostasis and warrant further research to define the regulation of
      metabolism and energy balance by ROS.

PMID- 21959342
TI  - Urinary F2-isoprostanes, obesity, and weight gain in the IRAS cohort.
AB  - Obesity has been associated with increased F(2)-isoprostane (F(2)-IsoP) levels
      cross-sectionally. However, the prospective association may be inverse, based on
      our earlier finding that elevated urinary F(2)-IsoP levels predict lower risk of
      diabetes. This earlier finding led us to hypothesize that urinary F(2)-IsoPs
      reflect the intensity of oxidative metabolism and as such predict lower risk of
      both diabetes and weight gain. We examined cross-sectional relationships with
      obesity and prospective relationships with weight gain using the data from 299
      participants of the Insulin Resistance Atherosclerosis Study (IRAS), all of whom
      were free of diabetes at baseline. Four urinary F(2)-IsoPs were assayed in stored
      baseline urine samples using liquid chromatography with tandem mass spectrometry:
      iPF(2alpha)-III, 2,3-dinor-iPF(2alpha)-III, iPF(2alpha)-VI, and 8,12-iso
      iPF(2alpha)-VI (F(2)-IsoP 1-4, respectively). Baseline F(2)-IsoPs were positively
      associated with baseline measures of obesity; the strongest associations were
      found with two F(2)-IsoPs: odds ratios (95% confidence intervals) for overall and
      abdominal obesity were 1.74 (1.26-2.40) and 1.63 (1.18-2.24) for F(2)-IsoP2 and
      1.47 (1.12-1.94) and 1.64 (1.22-2.20) for F(2)-IsoP4. F(2)-IsoP2 showed the
      strongest and significant inverse association with weight gain during the 5-year
      follow-up period: increase in F(2)-IsoP2 equal to 1 s.d. was associated with 0.90
      kg lower weight gain (P = 0.02) and the odds ratios for relative (>=5%) and
      absolute (>=5 kg) weight gain were 0.67 (0.47-0.96) and 0.57 (0.37-0.87),
      respectively. The other three F(2)-IsoPs were consistently inversely associated
      with weight gain, although not significantly, suggesting that different F(2)
      IsoPs vary in their ability to detect the association with weight gain.

PMID- 21959343
TI  - Incidental physical activity and sedentary behavior are not associated with
      abdominal adipose tissue in inactive adults.
AB  - The aim was to determine the association between objectively measured incidental
      physical activity (IPA) (i.e.,nonpurposeful activity accrued through activities
      of daily living) and sedentary behavior (SED) with abdominal obesity in a sample
      of inactive men and women. Participants were inactive, abdominally obese men (n =
      42; waist circumference (WC) >=102 cm) and women (n = 84; WC >=88 cm) recruited
      from Kingston, Canada. Physical activity and SED were determined by accelerometry
      over 7 days and summarized as IPA (accelerometer counts per min (cpm) >100),
      light physical activity (LPA; cpm 100-1951), sporadic moderate-to-vigorous
      physical activity (MVPA; cpm >=1,952, accumulated in bouts <10 consecutive
      minutes) and SED (cpm <100). Magnetic resonance imaging was used to acquire
      measures of abdominal obesity, visceral adipose tissue (VAT), and subcutaneous
      adipose tissue (ASAT). Participants spent on average 310.2 +/- 102.6 min/d in IPA
      and 627.8 +/- 86.9 min/d in SED. Neither IPA nor SED was associated with any
      measure of abdominal obesity (P > 0.1). Similarly, LPA was not a significant
      predictor of abdominal obesity whereas sporadic MVPA was negatively associated
      with VAT (P < 0.05) after control for age and sex. In this study, neither IPA nor
      SED was associated with abdominal obesity among inactive men and women.

PMID- 21959344
TI  - The association between socioeconomic status and obesity in Peruvian women.
AB  - Historically in developing countries, the prevalence of obesity has been greater
      in more advantaged socioeconomic groups. However, in recent years the association
      between socioeconomic status (SES) and obesity has changed and varies depending
      on the country's development stage. This study examines the relationship between
      SES and obesity using two indicators of SES: education or possession assets.
      Using the cross-sectional 2008 National Demographic and Family Health Survey of
      Peru (ENDES 2008), we investigated this relationship in women aged 15-49 years
      living in rural and urban settings. Descriptive, linear and logistic regressions
      analyses were conducted accounting for the multistage nature of the sampling
      design. The overall prevalence of obesity in this study was 14.1% (95% confidence
      interval (CI): 13.3-14.8); 8.4% (95% CI: 7.5-9.3) in rural areas and 16.2% (95%
      CI: 15.2-17.2) in urban areas. Wealthier women were more likely to be obese, and
      this association was stronger in rural areas. Conversely, more educated women
      were less likely to be obese, especially in urban areas. The distribution of
      obesity in Peruvian women is strongly related to socioeconomic position, and
      differs whether measured as possession assets or by level of education. These
      findings could have important implications for policy development in Peru.

PMID- 21959346
TI  - Impaired insulin-mediated antilipolysis and lactate release in adipose tissue of
      upper-body obese women.
AB  - Upper-body/visceral obesity is associated with abnormalities of free fatty acid
      (FFA) metabolism and greater risk of developing type 2 diabetes compared with
      lower-body obesity. In lean subjects lipolysis is readily suppressed by insulin;
      however, metabolic inflexibility with respect to antilipolysis is a frequent
      finding in obesity, partly determined by body composition. This study
      investigates effects of insulin on regional adipose tissue lipolysis and lactate
      levels in upper-body overweight/obese (UBO), lower-body overweight/obese (LBO),
      and lean women. The microdialysis technique was used to assess adipose tissue
      glycerol and lactate concentrations in abdominal and femoral fat during a 5-h
      basal period and a 2-h hyperinsulinemic euglycemic clamp. The main findings were
      that the antilipolytic effect of insulin was attenuated in abdominal fat of UBO
      (glycerol reduction, abd (%): UBO 40.4 (-14 to 66), LBO 46.0 (-8 to 66), lean
      66.2 (2-78), ANOVA, P < 0.05), and in femoral fat in both obese groups (glycerol
      reduction, fem (%): UBO 44.4 (35-67), LBO 44.4 (0-63), lean 65.0 (43-79), ANOVA,
      P < 0.05). Further, abdominal fat insulin-mediated increase in lactate
      concentration was greater in lean women compared with UBO women (lactate
      increase, abd (%): UBO -6.1 (-37.1 to 57.4), LBO 16.5 (-32.2 to 112.5), lean 51.4
      (-45.7 to 162.9), P < 0.05), whereas no differences were found between groups in
      femoral fat (lactate increase, fem (%), UBO -12.9 (-43 to 24), LBO 12.7 (-30.7 to
      92), lean 27.6 (-9.5 to 123.8), not significant). Respiratory exchange ratio
      (RER) increased significantly and similarly in all groups. So, UBO women were
      metabolically inflexible with respect to insulins antilipolytic and lactate
      increasing effects in abdominal adipose tissue. These phenomena are probably both
      consequences of insulin resistance of adipose tissue.

PMID- 21959345
TI  - Impact of the look AHEAD intervention on NT-pro brain natriuretic peptide in
      overweight and obese adults with diabetes.
AB  - Look AHEAD (Action for Health in Diabetes) is a randomized trial determining
      whether intensive lifestyle intervention (ILI) aimed at long-term weight loss and
      increased physical fitness reduces cardiovascular morbidity and mortality in
      overweight and obese individuals with type 2 diabetes compared to control
      (diabetes support and education, DSE). We investigated the correlates of N
      terminal pro-brain natriuretic peptide (NT-proBNP), a biomarker associated with
      heart failure (HF) risk, in a subsample from 15 of 16 participating centers and
      tested the hypothesis that ILI decreased NT-proBNP levels. Baseline and 1-year
      blood samples were assayed for NT-proBNP in a random sample of 1,500 without, and
      all 628 with, self-reported baseline CVD (cardiovascular disease) (N = 2,128).
      Linear models were used to assess relationships that log-transformed NT-proBNP
      had with CVD risk factors at baseline and that 1-year changes in NT-proBNP had
      with intervention assignment. At baseline, the mean (s.d.) age, BMI, and
      hemoglobin A(1c) (HbA(1c)) were 59.6 (6.8) years, 36.0 kg/m(2) (5.8), and 7.2%
      (1.1), respectively. Baseline geometric mean NT-proBNP was not different by
      condition (ILI 53.3 vs. DSE 51.5, P = 0.45), was not associated with BMI, and was
      inversely associated with HbA(1c). At 1 year, ILI participants achieved an
      average weight loss of 8.3% compared to 0.7% in DSE. At 1 year, NT-proBNP levels
      increased to a greater extent in the intervention arm (ILI +21.3% vs. DSE +14.2%,
      P = 0.046). The increased NT-proBNP associated with ILI was correlated with
      changes in HbA(1c), BMI, and body composition. In conclusion, among overweight
      and obese persons with diabetes, an ILI that reduced weight was associated with
      an increased NT-proBNP.

PMID- 21959347
TI  - Obesity-related derangements of coagulation and fibrinolysis: a study of obesity
      discordant monozygotic twin pairs.
AB  - Coagulation and fibrinolytic activities are under strong genetic control. We
      studied the effects of acquired obesity, independent of genetic factors on
      coagulation and fibrinolysis activities in obesity-discordant healthy monozygotic
      (MZ) twin pairs. Fourteen obesity-discordant (BMI within-pair difference >3
      kg/m(2)) and 10 concordant (BMI difference <2 kg/m(2)) MZ twin pairs were
      identified from the nationwide FinnTwin16 study. Body composition (dual-energy x
      ray absorptiometry), abdominal fat distribution (magnetic resonance imaging),
      liver fat (magnetic resonance spectroscopy), high sensitivity C-reactive protein,
      insulin sensitivity (euglycemic hyperinsulinemic clamp), and a panel of different
      markers of blood coagulation and fibrinolysis in the fasting state were measured.
      Strong resemblance was observed in most coagulation factors within all twin
      pairs, with the intraclass correlations ranging from 0.73 to 0.97, P < 0.03.
      However, the activities of fibrinogen and FIX, FXI, and FXII, and plasminogen
      activator inhibitor-1 (PAI-1) activities were increased in the obese co-twins (P
      < 0.05) and strongly correlated with the measures of adiposity, inflammation, and
      insulin resistance (r = 0.32-0.73, P < 0.05) among the twin individuals.
      Intrapair differences in fibrinogen and PAI-1 correlated with those in BMI,
      adiposity, and fasting insulin levels (r = 0.40-0.58, P < 0.05) indicating the
      independent effect of obesity. Derangements of blood coagulation and fibrinolysis
      are present already in early adulthood in obese subjects. Acquired obesity,
      independent of genetic factors, increases the activities of fibrinogen and
      activities of FIX, FXI, FXII, and PAI-1. This study confirms the mechanisms of
      simultaneous activities of intrinsic coagulation factors and impaired
      fibrinolysis predisposing obese subjects to thrombosis.

PMID- 21959348
TI  - Cross-sectional comparisons of BMI and waist circumference in British children:
      mixed public health messages.
AB  - Research suggests that there has been a leveling off in obesity prevalence
      occurring in the child population. However, a concern with the evidence base is
      that all of the studies have relied upon the use of BMI. The purpose of this
      study was to compare waist circumference (WC), BMI, and waist-to-height ratio
      (WHtR) data in three different sample of children (total number: 14,697)
      typically aged 11-12 years. Obesity prevalence defined by BMI did not change
      significantly between measurement years (2005 boys 20.6%, girls 18.0%; 2006 boys
      19.3%, girls 17.3%; 2007 boys 19.8%, girls 16.4%). Obesity prevalence defined by
      WC was considerably higher especially, in girls (2005 boys 26.3%, girls 35.6%;
      2006 boys 20.3%, girls 28.2%; 2007 boys 22.1%, girls 30.1%). The prevalence of
      children defined as "at risk" according to WHtR (2005 boys 23.3%, girls 21.1%;
      2006 boys 16.7%, girls 15.6%; 2007 boys 17.6%, girls 17.2%) was found to be
      between obesity prevalence, estimated using BMI and WC. This data are the most up
      to date collection that includes BMI and WC in three large samples of children
      and clearly demonstrates inconsistencies between different measurements based on
      current classification systems. There is a need to understand the relationship
      between BMI and WC, with growth and health risk to establish a consistent public
      health message that is easily understood by the public.

PMID- 21959349
TI  - Comparison of the quantitative performances and measurement uncertainty estimates
      obtained during method validation versus routine applications of a novel
      hydrophilic interaction chromatography method for the determination of cidofovir
      in human plasma.
AB  - Method validation is essential to ensure that an analytical method is fit for its
      intended purpose. Additionally, it is advisable to estimate measurement
      uncertainty in order to allow a correct interpretation of the results generated
      by analytical methods. Measurement uncertainty can be efficiently estimated
      during method validation as a top-down approach. However, method validation
      predictions of the quantitative performances of the assay and estimations of
      measurement uncertainty may be far away from the real performances obtained
      during the routine application of this assay. In this work, the predictions of
      the quantitative performances and measurement uncertainty estimations obtained
      from a method validation are compared to those obtained during routine
      applications of a bioanalytical method. For that purpose, a new hydrophilic
      interaction chromatography (HILIC) method was used. This method was developed for
      the determination of cidofovir, an antiviral drug, in human plasma. Cidofovir
      (CDV) is a highly polar molecule presenting three ionizable functions. Therefore,
      it is an interesting candidate for determination by HILIC mode. CDV is an acyclic
      cytidine monophosphate analog that has a broad antiviral spectrum and is
      currently undergoing evaluation in clinical trials as a topical agent for
      treatment of papillomavirus infections. The analytical conditions were optimized
      by means of design of experiments approach in order to obtain robust analytical
      conditions. These ones were absolutely necessary to enable the comparisons
      mentioned above. After a sample clean-up by means of solid phase extraction, the
      chromatographic analysis was performed on bare silica stationary phase using a
      mixture of acetonitrile-ammonium hydrogen carbonate (pH 7.0; 20mM) (72:28, v/v)
      as mobile phase. This newly developed bioanalytical method was then fully
      validated according to FDA (Food and Drug Administration) requirements using a
      total error approach that guaranteed that each future result will fall within
      acceptance limits of +/-30% with a probability of 95% over a concentration range
      of 92.7-1020ng/mL. A routine application of the cidofovir determination in two
      pre-clinical trials demonstrated that the prediction made during the pre-study
      validation was consistent by retrospective analysis of the quality control (QC)
      samples. Finally, comparison of the measurement uncertainty estimations
      calculated from the method validation with those obtained from the routine
      application of the method was performed, stressing that the estimations obtained
      during method validation underestimated those obtained from routine applications
      and that the magnitude of this underestimation was function of the cidofovir
      concentration. Finally, this new HILIC method is reliable, easily applicable to
      routine analysis and transposable at low cost in other laboratories.

PMID- 21959350
TI  - Determination of porcine fibrinogen in rat and dog plasma after intraperitoneal
      injection of a porcine-derived fibrin glue by fluorescein-labeled assay method:
      Comparison with isotope-labeled assay method.
AB  - A sensitive and specific fluorescein isothiocyanate (FITC) label coupled with
      size-exclusion high-performance liquid chromatography-fluorescence detection (SE
      HPLC-FLD) method was developed and validated for the estimation of the
      pharmacokinetic profiles of porcine fibrinogen after intraperitoneal injection of
      a porcine-derived fibrin glue (FG) to SD rats and beagle dogs with three single
      doses. Porcine fibrinogen, the major composition of the FG, was labeled with
      FITC. The FG containing FITC-labeled porcine fibrinogen was intraperitoneally
      administered to SD rats at three single dosages (100, 200, 400mg/kg of porcine
      fibrinogen), and the collected plasma was then detected by SE-HPLC-FLD method.
      The present technique was compared to the previously introduced isotope-labeled
      assay method for the pharmacokinetic studies in SD rats. The pharmacokinetic
      studies in SD rats showed that the correlation coefficient between the FITC
      labeled assay and (125)I-labeled assay methods was r(2)=0.989. Thus, this FITC
      labeled assay method performed well and demonstrated high concordance with the
      previous (125)I-labeled assay method, suggesting that FITC-labeled assay could
      substitute the (125)I-labeled assay as a method of choice for quantification in
      beagle dogs. Then the plasma levels of porcine fibrinogen in beagle dogs were
      studied by the FITC-labeled assay method with three single doses (15, 30, 60mg/kg
      of porcine fibrinogen). The method validation showed that the FITC label coupled
      with SE-HPLC-FLD method was suitable for the quantification of porcine fibrinogen
      in plasma samples with satisfactory linear (r(2)>0.999), precision (<12%),
      accuracy (95.5-104.9%) and recovery (>88%). The results showed linear disposition
      of porcine fibrinogen at the examined dosage range in SD rats or beagle dogs.

PMID- 21959351
TI  - Homocysteine--a stitch in time saves nine? A response to "A randomized placebo
      controlled trial of homocysteine lowering to reduce cognitive decline in older
      demented people." by Kwok et al. Clin Nutr 2011 Jan 7 [Epub ahead of print].

PMID- 21959352
TI  - Omega-3 polyunsaturated fatty acid and insulin sensitivity: a meta-analysis of
      randomized controlled trials.
AB  - BACKGROUND &AIM: n-3 PUFA has been shown to decrease the risk of several
      components of the metabolic syndrome; however, the role of n-3 PUFA on glucose
      metabolism is not clear. Our aim was to systematically review the effect of n-3
      PUFA on IS by conducting a meta-analysis of available RCTs. METHODS: We followed
      the guidelines of Cochrane's review of systematic interventions. We searched
      MEDLINE, EMBASE, CENTRAL and clinicaltrials.gov from the beginning of each
      database until October 2010. Meta-analysis was performed using a random effects
      model to estimate a pooled SMD and the corresponding 95% CI. RESULTS: From 303
      screened citations, 11 RCTs (n = 618) were eligible for inclusion in the
      analysis. In a pooled estimate, n-3 PUFA intervention had no effects on IS
      compared to placebo (SMD 0.08, 95% CI -0.11-0.28). Similarly, n-3 PUFA had no
      effects on IS in sub-group analyses (Type 2 diabetes vs. other population; QUICKI
      and other test subgroups). In the HOMA subgroup, n-3 PUFA was associated with a
      statistically significant increase in IS (SMD 0.30, CI 0.03-0.58) when compared
      to placebo. CONCLUSION: This meta-analysis is consistent with a lack of n-3 PUFA
      effects on IS.

PMID- 21959353
TI  - Optimising growth in phenylketonuria: current state of the clinical evidence
      base.
AB  - Patients with phenylketonuria (PKU) must follow a strict low-phenylalanine (Phe)
      diet in order to minimise the potentially disabling neuropsychological sequelae
      of the disorder. Research in this area has unsurprisingly focussed largely on
      managing blood Phe concentrations to protect the brain. Protein requirements in
      dietary management of PKU are met mostly from Phe-free protein substitutes with
      the intake of natural protein restricted to patient tolerance. Several reports
      have suggested that growth in early childhood in PKU is sub-optimal, relative to
      non-PKU control groups or reference populations. We reviewed the literature
      searching for evidence regarding PKU and growth as well as possible links between
      dietary management of PKU and growth. The search retrieved only limited evidence
      on the effect of PKU and its dietary management on growth. Physical development
      in PKU remains an under-studied aspect of this disorder.

PMID- 21959354
TI  - Non-invasive monitoring of cytotoxicity based on kinetic changes of cellular
      autofluorescence.
AB  - A quantitative, non-destructive cellular autofluorescence based in vitro imaging
      assay has been developed and applied to study the cytotoxicity of Sodium Lauryl
      Sulfate (SLS) and HgCl2 on Balb/c 3T3 cells. A phenomenological double logistic
      model was proposed to quantify and relate the observed kinetic changes of
      fluorescence to the toxic potency of chemical compounds. This work forms the
      basis for cellular autofluorescence measurements in in vitro toxicity screening
      assays.

PMID- 21959355
TI  - In brief: duration of use of bisphosphonates.

PMID- 21959356
TI  - Vemurafenib (Zelboraf) for metastatic melanoma.

PMID- 21959357
TI  - Prothrombin complex concentrates to reverse warfarin-related bleeding.

PMID- 21959358
TI  - Quetiapine (Seroquel) and QT-interval prolongation.

PMID- 21959359
TI  - Molecular genetic analysis of the APP, PSEN1, and PSEN2 genes in Finnish patients
      with early-onset Alzheimer disease and frontotemporal lobar degeneration.
AB  - Mutations in 3 genes, amyloid precursor protein (APP), presenilin 1 (PSEN1), and
      presenilin 2 (PSEN2), have been identified as causing a proportion of early-onset
      Alzheimer disease (eoAD) cases. A few PSEN mutations have also been previously
      detected in patients with frontotemporal lobar degeneration (FTLD). In order to
      evaluate the role of these genes in a clinical series of Finnish eoAD and FTLD
      patients, we sequenced exons 16 and 17 of the APP gene and the coding regions of
      the PSEN1 and PSEN2 genes in 140 eoAD and 66 FTLD patients. No pathogenic
      mutations were identified in the cohort. The E318G variant was detected with
      similar frequencies in the cases with eoAD and FTLD and the healthy controls,
      therefore, showing no association between E318G and eoAD. Furthermore, the PSEN2
      R71W variant seems to be nonpathogenic, because it was present in our healthy
      controls. Mutations in the PSEN1, PSEN2, and APP genes seem to be rare in this
      population, as these genes exhibited no pathogenic mutations in our cohort of
      eoAD and FTLD patients even though about 40% of the cases were familial ones.
      This suggests the involvement of other, still unknown genetic factors in the
      pathogenesis of these diseases.

PMID- 21959360
TI  - Long-standing prion dementia manifesting as posterior cortical atrophy.
AB  - Prion diseases commonly manifest with the phenotype of subacute myoclonic
      encephalopathy. However, genetic forms of prion disease may have prolonged
      evolution mimicking neurodegenerative disease. We present the clinical and
      neuropathological features of a family with an early and long-standing dementia
      manifesting with posterior cortical atrophy and related to a 120 bp insertional
      mutation of the prion protein gene. Two cases exhibited mixed prion and Abeta
      pathology. The differential diagnosis with Alzheimer disease is discussed.

PMID- 21959361
TI  - Dystypia without aphasia associated with visuospatial memory impairment in a
      patient with acute stroke.
AB  - Keyboard typing is a multifunctional task related to language, visual-spatial and
      motor abilities. If one of these functions is impaired, difficulty during typing
      could occur. Here, a 64-year-old right-handed man is reported who developed a
      sudden typing disturbance without aphasia or neglect. Magnetic resonance imaging
      of the brain showed discrete acute infarcts in the border-zone regions,
      bilaterally, predominantly in the left hemisphere. The neuropsychiatric testing
      showed an impaired visual-spatial memory domain; however, other cognitive
      functions were all normal. These findings suggest that visual-spatial memory
      impairment, associated with a left frontal subcortical infarct, is a probable
      anatomic substrate associated with the inability to type.

PMID- 21959362
TI  - Crossed aphasia in a dextral patient with logopenic/phonological variant of
      primary progressive aphasia.
AB  - BACKGROUND: Crossed aphasia is a rare phenomenon, with a prevalence of 1% to 2%
      among all right-handed patients. Two crossed aphasic patients with a nonfluent
      variant of primary progressive aphasia (PPA) have been reported previously. This
      report aims to document for the first time the occurrence of crossed logopenic
      progressive aphasia in a dextral patient. CASE REPORT: A 57-year-old monolingual
      housewife presented with word-finding difficulties. She was strongly right
      handed, had no clinical history for brain damage to the left hemisphere, and no
      left handers in her family history. Her language comprised simple, grammatically
      correct sentences with a fluctuating speech rate and intermittent word-finding
      pauses. Rare phonological errors were noted. Sentence repetition tasks showed
      impairments with grammatically complex sentences. Comprehension was intact as
      were writing and reading. The language disability remained isolated for 3 years.
      Cranial magnetic resonance imaging depicted somewhat asymmetrical atrophy of the
      parietal lobes (R>L), whereas single-photon-emitted computed tomographic imaging
      demonstrated hypoperfusion in the right parietal cortex, indicating right
      hemisphere dominance for language. CONCLUSIONS: This case report provides
      evidence that crossed PPA can present with a logopenic variant in addition to the
      nonfluent type demonstrated by others. Functional neuroimaging showed unexpected
      right-sided hypoperfusion in this case with only subtle structural brain
      asymmetry, implicating a reverse pattern of language dominance.

PMID- 21959363
TI  - Regional cerebral blood flow abnormalities associated with apathy and depression
      in Alzheimer disease.
AB  - The aim of this study was to identify brain areas related to apathy or depression
      in patients with Alzheimer disease (AD). Eighty-one AD patients were enrolled in
      this prospective study. (99m)Tc-HMPAO single photon emission computed tomography
      was performed to evaluate regional cerebral blood flow (rCBF). According to the
      Neuropsychiatric Inventory subscores of apathy and depression, 9 patients were
      classified as clinically significant (cs) depressed and non-cs-apathetic (D+)
      groups and 9 were classified as cs-apathetic and non-cs-depressed (A+) groups. In
      addition, 18 patients were classified as age-matched and Mini-Mental State
      Examination-matched disease control groups (D-, A-). The significance of rCBF
      differences between groups and the correlation between rCBF and subscores in 81
      AD patients were estimated by SPM (uncorrected P < 0.005) analysis. D+ patients
      had significantly lower perfusion in the right orbitofrontal and inferior frontal
      gyri than D- patients, whereas A+ patients had this in the right amygdala,
      temporal, posterior cingulate, right superior frontal, postcentral, and left
      superior temporal gyri than A- patients. The negatively correlated areas with
      depression subscores included the left inferior frontal and the right middle
      frontal gyri and those with apathy subscores included the right temporal and
      right medial frontal gyri. We suggest that this finding may indicate that apathy
      and depression in AD patients involve distinct functional circuits.

PMID- 21959364
TI  - Spatial summation and spatial discrimination of cold pain: effect of spatial
      configuration and skin type.
AB  - Spatial summation (SS) and spatial discrimination (SD) are essential for pain
      perception. In the cold-pain sensation, these processes have hardly been studied.
      Our aim was to study the SS and SD of cold pain, as well as the SS of cold-pain
      threshold (CPT) in hairy and glabrous skin. Two discrete stimuli (9 cm(2) each)
      were applied to the forearm with separation distances of 0-40 cm and in addition,
      a single stimulus on each forearm. For each configuration, the CPT,
      suprathreshold cold-pain ratings, and the reported number of activated stimuli
      (SD) were obtained. In another experiment, SS of CPT was tested in the hairy and
      glabrous skin of the hand using small (2.25 cm(2)) and large (9 cm(2)) probe
      sizes. The SS of CPT and of cold pain existed over separation distances of up to
      30-40 cm, at which point SD became better than chance. When the 2 forearms were
      stimulated, SS was abolished and cold pain was inhibited. CPT was significantly
      higher in hairy than glabrous skin, but the amount of SS of CPT was similar in
      the 2 skin types. Noxious cold-evoked thermal qualities were more common in the
      glabrous than the hairy skin. IN CONCLUSION: (1) SS and SD of cold pain are
      reciprocal; (2) whereas cold pain can summate over large distances, the SD of
      cold pain is poor; (3) SS of cold pain does not exist between contralateral body
      sides, however, inhibition occurs; (4) SS is independent of skin type and
      sensitivity to cold pain; (5) differences in pain quality between hairy and
      glabrous skin may reflect innervation differences.

PMID- 21959365
TI  - Thoracic respiratory motion estimation from MRI using a statistical model and a 2
      D image navigator.
AB  - Respiratory motion models have potential application for estimating and
      correcting the effects of motion in a wide range of applications, for example in
      PET-MR imaging. Given that motion cycles caused by breathing are only
      approximately repeatable, an important quality of such models is their ability to
      capture and estimate the intra- and inter-cycle variability of the motion. In
      this paper we propose and describe a technique for free-form nonrigid respiratory
      motion correction in the thorax. Our model is based on a principal component
      analysis of the motion states encountered during different breathing patterns,
      and is formed from motion estimates made from dynamic 3-D MRI data. We apply our
      model using a data-driven technique based on a 2-D MRI image navigator. Unlike
      most previously reported work in the literature, our approach is able to capture
      both intra- and inter-cycle motion variability. In addition, the 2-D image
      navigator can be used to estimate how applicable the current motion model is, and
      hence report when more imaging data is required to update the model. We also use
      the motion model to decide on the best positioning for the image navigator. We
      validate our approach using MRI data acquired from 10 volunteers and demonstrate
      improvements of up to 40.5% over other reported motion modelling approaches,
      which corresponds to 61% of the overall respiratory motion present. Finally we
      demonstrate one potential application of our technique: MRI-based motion
      correction of real-time PET data for simultaneous PET-MRI acquisition.

PMID- 21959366
TI  - Ocular manifestations of trichothiodystrophy.
AB  - OBJECTIVE: Trichothiodystrophy (TTD) is a rare, autosomal recessive disorder
      characterized by sulfur-deficient brittle hair and multisystem abnormalities.
      Many TTD patients have a defect in known DNA repair genes. This report
      systematically evaluates the ocular manifestations of the largest-to-date cohort
      of TTD patients and xeroderma pigmentosum (XP)/TTD patients. DESIGN: Case series.
      PARTICIPANTS: Thirty-two participants, ages 1 to 30 years, referred to the
      National Eye Institute for examination from 2001 to 2010; 25 had TTD and 7 had
      XP/TTD. METHODS: Complete, age- and developmental stage-appropriate ophthalmic
      examination. MAIN OUTCOME MEASURES: Visual acuity (VA), best-corrected VA, ocular
      motility, state of the ocular surface and corneal endothelial cell density,
      corneal diameter, and lens assessment. RESULTS: Developmental abnormalities
      included microcornea (44% TTD), microphthalmia (8% TTD, 14% XP/TTD), nystagmus
      (40% TTD), and infantile cataracts (56% TTD, 86% XP/TTD). Corrective lenses were
      required by 65% of the participants, and decreased best-corrected VA was present
      in 28% of TTD patients and 71% of XP/TTD patients. Degenerative changes included
      dry eye (32% TTD, 57% XP/TTD) and ocular surface disease identified by ocular
      surface staining with fluorescein (32% TTD) that usually are exhibited by much
      older patients in the general population. The 2 oldest TTD patients exhibited
      clinical signs of retinal/macular degeneration. Four XP/TTD patients presented
      with corneal neovascularization. CONCLUSIONS: These TTD and XP/TTD study
      participants had a wide variety of ocular findings including refractive error,
      infantile cataracts, microcornea, nystagmus, and dry eye/ocular surface disease.
      Although many of these can be ascribed to abnormal development--likely owing to
      abnormalities in basal transcription of critical genes--patients may also have a
      degenerative course. FINANCIAL DISCLOSURE(S): Proprietary or commercial
      disclosures may be found after the references.

PMID- 21959367
TI  - Limbal stem cell deficiency and ocular phenotype in ectrodactyly-ectodermal
      dysplasia-clefting syndrome caused by p63 mutations.
AB  - OBJECTIVE: To describe the ocular phenotype in patients with ectrodactyly
      ectodermal dysplasia-clefting (EEC) syndrome (MIM#604292) and to determine the
      pathogenic basis of visual morbidity. DESIGN: Retrospective case series.
      PARTICIPANTS: Nineteen families (23 patients) affected by EEC syndrome from the
      United Kingdom, Ireland, and Italy. METHODS: General medical examination to
      fulfill the diagnostic criteria for EEC syndrome and determine the phenotypic
      severity. Mutational analysis of p63 was performed by polymerase chain reaction
      based bidirectional Sanger sequencing. All patients with EEC syndrome underwent a
      complete ophthalmic examination and ocular surface assessment. Limbal stem cell
      deficiency (LSCD) was diagnosed clinically on the basis of corneal
      conjunctivalization and anatomy of the limbal palisades of Vogt. Impression
      cytology using immunofluorescent antibodies was performed in 1 individual.
      Histologic and immunohistochemical analyses were performed on a corneal button
      and corneal pannus from 2 EEC patients. MAIN OUTCOME MEASURES: The EEC syndrome
      phenotypic severity (EEC score), best-corrected Snellen visual acuity (decimal
      fraction), slit-lamp biomicroscopy, tear function index, tear breakup time, LSCD,
      p63 DNA sequence variants, impression cytology, and corneal histopathology.
      RESULTS: Eleven heterozygous missense mutations in the DNA binding domain of p63
      were identified in all patients with EEC syndrome. All patients had ocular
      involvement and the commonest was an anomaly of the meibomian glands and lacrimal
      drainage system defects. The major cause of visual morbidity was progressive
      LSCD, which was detected in 61% (14/23). Limbal stem cell deficiency was related
      to advancing age and caused a progressive keratopathy, resulting in a dense
      vascularized corneal pannus, and eventually leading to visual impairment.
      Histologic analysis and impression cytology confirmed LSCD. CONCLUSIONS:
      Heterozygous p63 mutations cause the EEC syndrome and result in visual impairment
      owing to progressive LSCD. There was no relationship of limbal stem cell failure
      with the severity of EEC syndrome, as classified by the EEC score, or the
      underlying molecular defect in p63. FINANCIAL DISCLOSURE(S): The authors have no
      proprietary or commercial interest in any of the materials discussed in this
      article.

PMID- 21959369
TI  - Reliability of estimating ductions in thyroid eye disease: an International
      Thyroid Eye Disease Society multicenter study.
AB  - PURPOSE: To determine intraobserver and interobserver reliability of 3 clinical
      techniques for measuring ocular ductions in patients with thyroid eye disease and
      to compare these with an established method using a Goldmann perimeter. Our
      secondary goals were to compare the clinical methods for test duration, ease of
      learning and performance, and whether these differed between novices and experts.
      DESIGN: Multicenter, prospective, comparative trial. PARTICIPANTS: We recruited
      38 patients with thyroid orbitopathy and reduced ocular motility from 7 academic
      centers. METHODS: At each center, 2 novices and 2 experts measured the ocular
      ductions of each eye of each patient in 4 directions (0 degrees , 90 degrees ,
      180 degrees , and 270 degrees ) using 3 techniques (best guess [BG], light reflex
      [LR], and a ruler measuring [RU] technique). Test duration and clinicians'
      feedback were recorded. A subjective and objective measurement for ocular
      ductions using a Goldmann perimeter was performed for each subject by a trained
      technician. The 3 clinical measurements and the perimetry measurements were
      performed twice, separated by >=1 hour. MAIN OUTCOME MEASURES: We measured the
      intraobserver and interobserver reliability of the 3 clinical techniques and
      intraobserver reliability of Goldmann perimeter. Clinical testing reliability was
      compared between experts and novices. We also examined test duration and
      clinician feedback. RESULTS: The LR technique had significantly better
      intraobserver and interobserver repeatability compared with the BG or RU clinical
      measurements and statistically was equivalent to the gold-standard perimetric
      technique. Reliability was constant regardless of the amount of restriction in
      ocular movement. There was no difference between reliability values for experts
      and novices. The LR and BG techniques were significantly faster than the RU or
      perimetry techniques and were considered easiest to learn and perform, but
      clinicians had most confidence in the LR technique results. CONCLUSIONS: The LR
      technique for measuring ocular ductions in thyroid orbitopathy is more reliable
      than other clinical techniques and as reliable as the established technique using
      the perimeter. However, unlike the latter method, it is easier to learn and
      perform by both novices and experts, is significantly faster, and can be
      performed by the clinician without machinery or a trained technician.

PMID- 21959368
TI  - Clinical characteristics in 53 patients with cat scratch optic neuropathy.
AB  - OBJECTIVE: To describe the clinical manifestations and to identify risk factors
      associated with visual outcome in a large cohort of patients with cat scratch
      optic neuropathy (CSON). DESIGN: Multicenter, retrospective chart review.
      PARTICIPANTS: Fifty-three patients (62 eyes) with serologically positive CSON
      from 5 academic neuro-ophthalmology services evaluated over an 11-year period.
      METHODS: Institutional review board/ethics committee approval was obtained. Data
      from medical record charts were collected to detail the clinical manifestations
      and to analyze visual outcome metrics. Generalized estimating equations and
      logistic regression analysis were used in the statistical analysis. Six patients
      (9 eyes) were excluded from visual outcome statistical analysis because of a lack
      of follow-up. MAIN OUTCOME MEASURES: Demographic information, symptoms at
      presentation, clinical characteristics, length of follow-up, treatment used, and
      visual acuity (at presentation and final follow-up). RESULTS: Mean patient age
      was 27.8 years (range, 8-65 years). Mean follow-up time was 170.8 days (range, 1
      1482 days). Simultaneous bilateral involvement occurred in 9 (17%) of 53
      patients. Visual acuity on presentation ranged from 20/20 to counting fingers
      (mean, 20/160). Sixty-eight percent of eyes retained a visual acuity of 20/40 or
      better at final follow-up (defined as favorable visual outcome). Sixty-seven
      percent of patients endorsed a history of cat or kitten scratch. Neuroretinitis
      (macular star) developed in 28 eyes (45%). Only 5 patients had significant visual
      complications (branch retinal artery occlusion, macular hole, and corneal
      decompensation). Neither patient age nor any other factor except good initial
      visual acuity and absence of systemic symptoms was associated with a favorable
      visual outcome. There was no association between visual acuity at final follow-up
      and systemic antibiotic or steroid use. CONCLUSIONS: Patients with CSON have a
      good overall visual prognosis. Good visual acuity at presentation was associated
      with a favorable visual outcome. The absence of a macular star does not exclude
      the possibility of CSON. FINANCIAL DISCLOSURE(S): The author(s) have no
      proprietary or commercial interest in any materials discussed in this article.

PMID- 21959370
TI  - Ocular motor and sensory function in Parkinson's disease.
AB  - PURPOSE: To evaluate the effect of dopaminergic medication and deep brain
      stimulation on ocular function in Parkinson's disease (PD) and to measure vision
      related quality of life in subjects with PD. DESIGN: Prospective, comparative
      case series. PARTICIPANTS AND CONTROLS: Twenty-seven PD and 16 control subjects
      were recruited. METHODS: Visual acuity, ocular motor function, convergence, and
      vision-related quality of life using the 25-item National Eye Institute Visual
      Function Questionnaire (VFQ-25) were measured. Visual sensory and motor
      measurements were obtained during the on and off states of PD dopaminergic
      treatment. MAIN OUTCOME MEASURES: Convergence ability and vision-related quality
      of life. RESULTS: The PD subjects had a mean age of 58.8 years; 30% were female.
      Their mean duration of PD was 10.9 +/- 6.8 years. The control subjects had a mean
      age of 61.6 years; 56% were female. There was no difference in visual acuity,
      contrast sensitivity, or color vision of the PD subjects in their on state
      compared with controls. Convergence amplitudes measured with base-out prism were
      significantly poorer in PD subjects in their on state compared with controls
      (24.1 +/- 8 Delta vs. 14.8 +/- 10.3 Delta; P = 0.003). The mean composite VFQ-25
      score was significantly worse in the PD subjects compared with the controls (87.1
      +/- 8.69 vs. 96.6 +/- 3.05; P = 0.0001). Comparing the PD subjects in their on
      with their off states, there was no difference in distance exodeviation, near
      exodeviation, or ocular ductions. Mean convergence amplitudes and near point of
      convergence were better in the on state compared with the off state: 14.8 +/-
      10.3 Delta versus 10.7 +/- 9.0 Delta (P = 0.0006) and 13.1 +/- 9.1 cm versus 18.1
      +/- 12.2 cm (P = 0.002), respectively. CONCLUSIONS: Convergence ability is
      significantly poorer in PD subjects in both the on and off states compared with
      controls, but improves significantly with systemic dopaminergic treatment. Ocular
      motor function in PD subjects fluctuates in response to treatment, which
      complicates ophthalmic management. Parkinson's disease subjects have a
      significant reduction in vision-related quality of life, especially with near
      activities, that is not associated with visual acuity. FINANCIAL DISCLOSURE(S):
      The author(s) have no proprietary or commercial interest in any materials
      discussed in this article.

PMID- 21959371
TI  - Optical treatment of strabismic and combined strabismic-anisometropic amblyopia.
AB  - OBJECTIVE: To determine visual acuity improvement in children with strabismic and
      combined strabismic-anisometropic (combined-mechanism) amblyopia treated with
      optical correction alone and to explore factors associated with improvement.
      DESIGN: Prospective, multicenter, cohort study. PARTICIPANTS: We included 146
      children 3 to <7 years old with previously untreated strabismic amblyopia (n =
      52) or combined-mechanism amblyopia (n = 94). METHODS: Optical treatment was
      provided as spectacles (prescription based on a cycloplegic refraction) that were
      worn for the first time at the baseline visit. Visual acuity with spectacles was
      measured using the Amblyopia Treatment Study HOTV visual acuity protocol at
      baseline and every 9 weeks thereafter until no further improvement in visual
      acuity. Ocular alignment was assessed at each visit. MAIN OUTCOME MEASURES:
      Visual acuity 18 weeks after baseline. RESULTS: Overall, amblyopic eye visual
      acuity improved a mean of 2.6 lines (95% confidence interval [CI], 2.3-3.0), with
      75% of children improving >= 2 lines and 54% improving >= 3 lines. Resolution of
      amblyopia occurred in 32% (95% CI, 24%-41%) of the children. The treatment effect
      was greater for strabismic amblyopia than for combined-mechanism amblyopia (3.2
      vs 2.3 lines; adjusted P = 0.003). Visual acuity improved regardless of whether
      eye alignment improved. CONCLUSIONS: Optical treatment alone of strabismic and
      combined-mechanism amblyopia results in clinically meaningful improvement in
      amblyopic eye visual acuity for most 3- to <7-year-old children, resolving in at
      least one quarter without the need for additional treatment. Consideration should
      be given to prescribing refractive correction as the sole initial treatment for
      children with strabismic or combined-mechanism amblyopia before initiating other
      therapies. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial
      interest in any of the materials discussed in this article.

PMID- 21959372
TI  - Laser in situ keratomileusis for the treatment of refractive accommodative
      esotropia.
AB  - PURPOSE: To demonstrate the effectiveness of refractive surgery with an excimer
      laser to correct hyperopia and convergent strabismus caused by compensatory
      accommodation of refractive error. DESIGN: Prospective, interventional,
      noncomparative case series. PARTICIPANTS: Forty-six eyes of 23 patients with
      hyperopia and fully or partially refractive accommodative esotropia. METHODS:
      Patients were treated with an excimer laser and the LASIK technique between 2000
      and 2010. MAIN OUTCOME MEASURES: Preoperative and postoperative refractive
      spherical equivalent and ocular alignment. RESULTS: Mean age +/- standard
      deviation [SD] was 25 +/- 12.6 years. Mean hyperopia +/- SD was 3.67 +/- 1.28
      diopters (D) before surgery and 0.21 +/- 0.59 D after surgery (P<0.001). The mean
      angle of deviation without correction was 21.0 prism diopters (Delta) before
      surgery and 3.7 Delta after surgery (P<0.001). CONCLUSIONS: Refractive surgery
      with excimer laser is a promising option for the treatment of refractive
      accommodative esotropia. FINANCIAL DISCLOSURE(S): The author(s) have no
      proprietary or commercial interest in any materials discussed in this article.

PMID- 21959373
TI  - Risk models for progression to advanced age-related macular degeneration using
      demographic, environmental, genetic, and ocular factors.
AB  - PURPOSE: To expand our predictive models for progression to advanced stages of
      age-related macular degeneration (AMD) based on demographic, environmental,
      genetic, and ocular factors, using longer follow-up, time varying analyses,
      calculation of absolute risks, adjustment for competing risks, and detailed
      baseline AMD and drusen status. DESIGN: Prospective, longitudinal study.
      PARTICIPANTS: We included 2937 individuals in the Age-Related Eye Disease Study,
      of which 819 subjects progressed to advanced AMD during 12 years of follow-up.
      METHODS: Cox proportional hazards regression analyses were performed to calculate
      hazard ratios for progression. Covariates included demographic and environmental
      factors, 6 variants in 5 genes, baseline macular drusen size, and presence and
      type of advanced AMD in 1 eye at baseline. To assess the ability of risk scores
      based on all covariates to discriminate between progressors and nonprogressors,
      an algorithm was developed and the area under the receiver operating
      characteristic curve (AUC) was calculated. To validate the overall model, the
      total sample was randomly subdivided into derivation and test samples. Another
      model was built based on the derivation sample and assessed for calibration and
      discrimination in the test sample. Sample sizes needed for testing new treatments
      in clinical trials were estimated based on models with and without genetic
      variables. MAIN OUTCOME MEASURES: Progression to advanced AMD, including
      geographic atrophy and neovascular disease. RESULTS: In multivariate models, age,
      smoking, body mass index, single nucleotide polymorphisms in the CFH,
      ARMS2/HTRA1, C3, C2, and CFB genes, as well as presence of advanced AMD in 1 eye
      and drusen size in both eyes were all independently associated with progression.
      The AUC for progression at 10 years in the model with genetic factors, drusen
      size, and environmental covariates was 0.915 in the total sample. In the test
      sample, based on a model estimated from the derivation sample, the AUC was 0.908.
      The sample sizes needed for clinical trials were estimated to be lower when
      genetic susceptibility was considered. CONCLUSIONS: Factors reflective of nature
      and nurture were incorporated into an expanded algorithm for risk prediction,
      which performed very well in both derivation and test samples. Risk scores and
      predicted progression rates will be useful for AMD surveillance and for designing
      clinical trials. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure
      may be found after the references.

PMID- 21959374
TI  - Amino acid based chiral N-amidothioureas. Acetate anion binding induced chirality
      transfer.
AB  - N-Amidothioureas generated from amine-dimethylated natural L-phenylalanine and
      its D-enantiomer bearing a chiral carbon that is by 2 atoms or 3 chemical bonds
      away from the anion binding site establish chiral communication upon acetate
      anion binding to the thiourea moiety.

PMID- 21959376
TI  - Mass-producible superhydrophobic surfaces.
AB  - Mass-producible superhydrophobic surfaces with remarkably identical appearance
      and efficiency through a mold fabrication and hot embossing process are reported.

PMID- 21959375
TI  - Modelling a ciliopathy: Ahi1 knockdown in model systems reveals an essential role
      in brain, retinal, and renal development.
AB  - Joubert syndrome and related diseases (JSRD) are cerebello-oculo-renal syndromes
      with phenotypes including cerebellar hypoplasia, retinal dystrophy, and
      nephronophthisis (a cystic kidney disease). Mutations in AHI1 are the most common
      genetic cause of JSRD, with developmental hindbrain anomalies and retinal
      degeneration being prominent features. We demonstrate that Ahi1, a WD40 domain
      containing protein, is highly conserved throughout evolution and its expression
      associates with ciliated organisms. In zebrafish ahi1 morphants, the phenotypic
      spectrum of JSRD is modeled, with embryos showing brain, eye, and ear
      abnormalities, together with renal cysts and cloacal dilatation. Following ahi1
      knockdown in zebrafish, we demonstrate loss of cilia at Kupffer's vesicle and
      subsequently defects in cardiac left-right asymmetry. Finally, using siRNA in
      renal epithelial cells we demonstrate a role for Ahi1 in both ciliogenesis and
      cell-cell junction formation. These data support a role for Ahi1 in epithelial
      cell organization and ciliary formation and explain the ciliopathy phenotype of
      AHI1 mutations in man.

PMID- 21959377
TI  - Rational design to improve thermostability and specific activity of the truncated
      Fibrobacter succinogenes 1,3-1,4-beta-D-glucanase.
AB  - 1,3-1,4-beta-D-Glucanase has been widely used as a feed additive to help non
      ruminant animals digest plant fibers, with potential in increasing nutrition
      turnover rate and reducing sanitary problems. Engineering of enzymes for better
      thermostability is of great importance because it not only can broaden their
      industrial applications, but also facilitate exploring the mechanism of enzyme
      stability from structural point of view. To obtain enzyme with higher
      thermostability and specific activity, structure-based rational design was
      carried out in this study. Eleven mutants of Fibrobacter succinogenes 1,3-1,4
      beta-D-glucanase were constructed in attempt to improve the enzyme properties. In
      particular, the crude proteins expressed in Pichia pastoris were examined firstly
      to ensure that the protein productions meet the need for industrial fermentation.
      The crude protein of V18Y mutant showed a 2  degrees C increment of Tm and W203Y
      showed ~30% increment of the specific activity. To further investigate the
      structure-function relationship, some mutants were expressed and purified from P.
      pastoris and Escherichia coli. Notably, the specific activity of purified W203Y
      which was expressed in E. coli was 63% higher than the wild-type protein. The
      double mutant V18Y/W203Y showed the same increments of Tm and specific activity
      as the single mutants did. When expressed and purified from E. coli, V18Y/W203Y
      showed similar pattern of thermostability increment and 75% higher specific
      activity. Furthermore, the apo-form and substrate complex structures of
      V18Y/W203Y were solved by X-ray crystallography. Analyzing protein structure of
      V18Y/W203Y helps elucidate how the mutations could enhance the protein stability
      and enzyme activity.

PMID- 21959378
TI  - Engineered biosynthesis of glycosylated derivatives of narbomycin and evaluation
      of their antibacterial activities.
AB  - A 14-membered macrolide antibiotic narbomycin produced from Streptomyces
      venezuelae ATCC 15439 is composed of polyketide macrolactone ring and D
      desosamine as a deoxysugar moiety, which acts as an important determinant of its
      antibacterial activity. In order to generate diverse glycosylated derivatives of
      narbomycin, expression plasmids carrying different deoxysugar biosynthetic gene
      cassettes and the gene encoding a substrate-flexible glycosyltransferase DesVII
      were constructed and introduced into S. venezuelae YJ003 mutant strain bearing a
      deletion of thymidine-5'-diphospho-D-desosamine biosynthetic gene cluster. The
      resulting recombinants of S. venezuelae produced a range of new analogs of
      narbomycin, which possess unnatural sugar moieties instead of native deoxysugar D
      desosamine. The structures of narbomycin derivatives were determined through
      nuclear magnetic resonance spectroscopy and mass spectrometry analyses and their
      antibacterial activities were evaluated in vitro against erythromycin-susceptible
      and -resistant Enterococcus faecium and Staphylococcus aureus. Substitution with
      L-rhamnose or 3-O-demethyl-D-chalcose was demonstrated to exhibit greater
      antibacterial activity than narbomycin and the clinically relevant erythromycin.
      This work provides new insight into the functions of deoxysugar biosynthetic
      enzymes and structure-activity relationships of the sugar moieties attached to
      the macrolides and demonstrate the potential of combinatorial biosynthesis for
      the generation of new macrolides carrying diverse sugars with increased
      antibacterial activities.

PMID- 21959379
TI  - First-in-human experience with the Medtronic Bifurcation Stent System.
AB  - AIMS: The BRANCH study was a prospective, multicentre, non-randomised, single arm
      trial to investigate the feasibility, safety, efficacy, and performance of the
      bare metal Medtronic Bifurcation Stent System for the treatment of de novo
      bifurcation lesions. METHODS AND RESULTS: Sixty patients were enrolled in the
      study. After a learning curve of one case at seven centres, 53 patients from six
      centres were prospectively treated. The primary endpoint was target vessel
      failure (TVF) at 30 days. Secondary endpoints included acute device, lesion, and
      procedure success and TVF at 12 months. Medina complex bifurcation lesions
      (1,1,1; 1,1,0; 1,0,1; 0,1,1) were treated in 71.7%. The stent was successfully
      implanted in 86.8% of cases. Acute device, lesion, and procedure success rates
      were 83.0%, 92.5%, and 88.7%, respectively. TVF occurred in 2/52 patients (3.8%)
      at 30 days. No other major adverse cardiac adverse events (MACE) occurred through
      30 days follow-up. At 12 months, TVF occurred in 6/47 (12.8%) patients, and MACE
      occurred in 5/47 (10.6%) patients. CONCLUSIONS: Results from the BRANCH study
      demonstrate that the Medtronic Bifurcation Stent System is safe and can be
      successfully and effectively deployed in a variety of bifurcation lesions with
      good clinical outcomes.

PMID- 21959380
TI  - Rapid and simultaneous determination of hexapeptides (Ac-EEMQRR-amide and H2N
      EEMQRR-amide) in anti-wrinkle cosmetics by hydrophilic interaction liquid
      chromatography-solid phase extraction preparation and hydrophilic interaction
      liquid chromatography with tandem mass spectrometry.
AB  - A rapid method for the simultaneous determination of Ac-EEMQRR-amide and H(2)N
      EEMQRR-amide in cosmetic products was developed and evaluated. This analytical
      procedure involved extracting samples with 0.1:0.1:85:15 (v:v) trifluoroacetic
      acid (TFA):formic acid:acetonitrile (ACN):water and determination by hydrophilic
      interaction liquid chromatography with tandem mass spectrometry (HILIC-MS/MS).
      Samples showing serious ion suppression were further cleaned up using HILIC-SPE
      prior to HILIC-MS/MS analysis. Stable isotopically labeled peptides,
      corresponding to the above two peptides, were used as internal standards to
      correct for loss of recovery and matrix effects. Electrospray ionization (ESI) in
      the positive mode was used. The linear range was 2.0-1000 ng/mL for Ac-EEMQRR
      amide and 25.0-2500 ng/mL for H(2)N-EEMQRR-amide. Thirteen commercial products
      were analyzed for the two peptides using this method. The amounts of Ac-EEMQRR
      amide in the samples ranged from none detected to 42.3 MUg/g. H(2)N-EEMQRR-amide
      was not detected in any of the samples. The recoveries for Ac-EEMQRR-amide and
      H(2)N-EEMQRR-amide ranged from 85% to 110% and 84% to 119%, respectively, at the
      spiking level of 30 MUg/g.

PMID- 21959381
TI  - Fine mapping of 14q24.1 breast cancer susceptibility locus.
AB  - In the National Cancer Institute Cancer Genetic Markers of Susceptibility (CGEMS)
      genome-wide association study of breast cancer, a single nucleotide polymorphism
      (SNP) marker, rs999737, in the 14q24.1 interval, was associated with breast
      cancer risk. In order to fine map this region, we imputed a 3.93 MB region
      flanking rs999737 for Stages 1 and 2 of the CGEMS study (5,692 cases, 5,576
      controls) using the combined reference panels of the HapMap 3 and the 1000
      Genomes Project. Single-marker association testing and variable-sized sliding
      window haplotype analysis were performed, and for both analyses the initial
      tagging SNP rs999737 retained the strongest association with breast cancer risk.
      Investigation of contiguous regions did not reveal evidence for an additional
      independent signal. Therefore, we conclude that rs999737 is an optimal tag SNP
      for common variants in the 14q24.1 region and thus narrow the candidate variants
      that should be investigated in follow-up laboratory evaluation.

PMID- 21959382
TI  - Exome sequencing and subsequent association studies identify five amino acid
      altering variants influencing human height.
AB  - Height is a highly heritable trait that involves multiple genetic loci. To
      identify causal variants that influence stature, we sequenced whole exomes of
      four children with idiopathic short stature. Ninety-five nonsynonymous single
      nucleotide polymorphisms (nsSNPs) were selected as potential candidate variants.
      We performed association analysis in 740 cohort individuals and identified 11
      nsSNPs in 10 loci (DIS3L2, ZBTB38, FAM154A, PTCH1, TSSC4, KIF18A, GPR133, ACAN,
      FAM59A, and NINL) associated with adult height (P < 0.05), including five novel
      loci. Of these, two nsSNPs (TSSC4 and KIF18A loci) were significant at P < 0.05
      in the replication study (n = 1,000) and five (ZBTB38, FAM154A, TSSC4, KIF18A,
      and FAM59A loci) were significant at P < 0.01 in the combined analysis (n =
      1,740). Together, the five nsSNPs accounted for approximately 2.5% of the height
      variation. This study demonstrated the utility of next-generation sequencing in
      identifying genetic variants and loci associated with complex traits.

PMID- 21959383
TI  - Quality performance with evidence and the focus shift.

PMID- 21959384
TI  - Postearthquake plastic surgery mission trip to Port-au-Prince, Haiti: a medical
      student's perspective.

PMID- 21959385
TI  - Image-guided navigation in optimizing surgical management of craniomaxillofacial
      fibrous dysplasia.
AB  - BACKGROUND: Fibrous dysplasia is a benign developmental dysplastic disorder of
      the bone in which abnormal fibroblastic proliferation replaces the normal bone
      matrix. Craniomaxillofacial fibrous dysplasia can cause severe deformity with
      devastating functional and aesthetic consequence. Precise surgical removal of the
      fibro-osseous tissue is the key to ultimately restore normal function and
      aesthetics. Navigational surgical tool has become a useful adjunct in the
      surgical management of the craniomaxillofacial skeleton. METHODS: Thirteen
      patients with facial asymmetry and deformity caused by craniomaxillofacial
      fibrous dysplasia were enrolled into this study. With preoperative planning and
      three-dimensional simulation, normal anatomic contours of the deformed area were
      recreated by superimposing unaffected to the affected side. After registration,
      surgical facial recontouring was performed under the guidance of navigation
      system. RESULTS: Good accuracy was achieved with the registration of patient's
      facial skeleton and preoperative three-dimensional reconstructed model in all the
      cases. With intraoperative navigational guidance, facial bone recontouring was
      performed uneventfully in all cases. Surgical accuracy was evaluated by comparing
      the preoperative and postoperative computed tomography scan measurement. The mean
      maximum discrepancy between the actual surgical reduction and preoperative
      planning was less than 2 mm. Symptoms associated with optical nerve compression
      were eliminated in affected individuals. All patients' facial symmetry and
      aesthetics were improved. CONCLUSION: Navigation-guided facial bone recontouring
      is a valuable treatment modality in managing craniomaxillofacial fibrous
      dysplasia.

PMID- 21959386
TI  - Biologic filler using human fibroblasts and placenta extracts.
AB  - Soft tissue augmentation with injectable materials has been a challenging problem
      for plastic and reconstructive surgeons. Although filler materials have been used
      for soft tissue augmentation, adverse effects such as inflammation, distortion,
      and repeated procedures due to absorption still exist. In this study, biologic
      filler containing human fibroblasts and placenta extracts was developed to
      overcome these problems as a concept of cell therapy.In an in vivo assay, 40 nude
      mice were divided into 4 groups: 1 control group and 3 experimental groups.
      Biologic fillers containing human fibroblasts untreated (control), cultured with
      0.1% placenta extract (group 1), cultured with 10% fetal bovine serum (group 2),
      and cultured with both 0.1% placenta extract and 10% fetal bovine serum (group 3)
      were used in each groups. Cultured human fibroblasts were injected into the back
      of each mouse with fibrin glue to maintain the shape and volume. These groups
      were compared during an 8-week period. The gross, histologic, and biomolecular
      studies were proceeded to evaluate the effect of biologic filler.In geometric
      maintenance, volumes in experimental groups were 1.6 (group 1), 1.2 (group 2),
      and 1.9 times (group 3) more reserved than that in the untreated control group
      (control) at 8 weeks. In histology, abundant proliferation of fibroblasts as well
      as extracellular matrices including collagen and glycosaminoglycan was visualized
      in experimental groups. Enzyme-linked immunosorbent assay was used to analyze
      collagen and glycosaminoglycan, and reverse transcription-polymerase chain
      reaction was used to analyze the messenger RNA expression of COL1A1, a gene for
      collagen type 1, which shows a significant difference between control and
      experimental groups. There is no statistically significant difference between
      groups 1 and 2; on the other hand, group 3 statistically has the best outcome
      among the experimental groups.

PMID- 21959387
TI  - Management of maxillofacial injuries in Iraq.
AB  - These clinical studies reflect the experience of the author in managing 673
      patients treated during the last 8 years. All patients were treated in the
      Maxillofacial Unit, Surgical Specialties Hospital, Medical City, Baghdad, and in
      the author's private clinic. Included patients were 530 males and 143 females;
      patients' age ranged between 1 year and 75 years (mean, 38 y). Distribution of
      injuries was as follows: fracture of the mandible, 287 (42.64%); middle third
      injuries, 39 (5.79%); orbital injuries, 236 (35.07%; including 12 cases with
      cranioorbital injuries); injuries in children, 27 (4.0%); fracture of the zygoma,
      52 (7.73%); and fracture of the nose, 40 (5.94%).Maxillofacial injuries in this
      study were classified as follows: (1) craniomaxillofacial with head injuries and
      cerebrospinal fluid leak; (2) fracture of the middle third including Le Fort I,
      II, and III and midline split in the face; (3) fracture of the mandible as an
      isolated injury or as part of a facial skeleton injury; and (4) isolated complex
      injuries of the zygoma, the orbital skeleton, and the nasoethmoidal region.The
      technique used for treating middle third injuries was external fixation either by
      halo frame (with vertical rods and cheek wires) or by box frame (using 4 external
      pins connected by rods) or internal fixation by suspending the middle third with
      internal wires (0.5 mm stainless steel) from the zygomatic process of the frontal
      bone beneath the zygomatic arch down the lower arch bar. Fractures of the
      mandible were treated by gunning splint with intermaxillary fixation (IMF) or
      with open reduction and fixation by stainless steel wire with IMF or by IMF screw
      or by an arch bar and IMF. Other fractures such as fracture of the orbit were
      treated by bone graft, sialastic, or lyophilized dura with open reduction.
      Fractures of the zygoma were treated by open reduction and fixation with
      stainless steel wire and bone graft or by reduction without fixation. Fractures
      of the nose were treated by reduction with straightening of the septum with a
      splint (lead splint or polythene) or by external splint with plaster of Paris.
      With the techniques used, results from managing these cases were satisfactory.

PMID- 21959388
TI  - Role of apoptosis in retinoic acid-induced cleft palate.
AB  - PURPOSE: Although the mechanism by which retinoic acid (RA) induces cleft palate
      has been intensely investigated, some controversies remain. Some researchers
      argue that RA inhibits apoptosis, resulting in a failure of palatal shelves to
      fuse, whereas others propose that RA disrupts elevation or retards the growth of
      palatal shelves. This study investigated the mechanism underlying RA-induced
      formation of cleft palate in the rat, focusing mainly on the role of apoptosis.
      METHODS: Using an RA-induced cleft palate model of Sprague-Dawley rats described
      in our previous study, we examined a total of 92 embryos. Retinoic acid was
      injected intraperitoneally in experimental group animals on embryonic day 11
      (D11), a time when our previous study indicated that RA-induced cleft palate was
      maximally developed. Control animals were treated with normal saline mixed with
      sesame oil. Timed pregnant rats were killed by an overdose of ether on D13, D14,
      D15, D16, and D17, and 8 sections were prepared from the anterior to the
      posterior of the palate. Growth of palatal shelves was evaluated histologically
      by examining sections stained with hematoxylin-eosin, periodic acid-Schiff,
      trichrome, and cresyl violet. Differences in apoptosis were monitored using
      terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assays.
      RESULTS: Histologic examinations revealed underdevelopment of palatal shelves in
      the experimental group compared with the control group. In the RA-treated group,
      the overall process of palatal shelf development was delayed 1 day, and palatal
      elevation was observed. In hard-palate areas of both groups, apoptosis was
      maximal immediately after the fusion of palatal shelves. In the soft-palate
      areas, the saline-treated group showed fusion of palatal shelves, whereas the RA
      treated group showed retarded growth of palatal shelves that resulted in failure
      of palatal fusion. Moreover, apoptosis occurred before palatal contact.
      CONCLUSIONS: Apoptotic manifestations did not differ between RA-induced cleft
      palates and control palates, suggesting that apoptosis makes a minimal
      contribution to the cleft palate formed in response to RA. Instead, growth
      retardation of the palatal shelves appears to play a major role in RA-induced
      cleft palate.

PMID- 21959389
TI  - Commentary on role of apoptosis in retinoic Acid-induced cleft palate.

PMID- 21959390
TI  - Optical properties of pigmented polydimethylsiloxane prosthetic elastomers:
      effect of "outdoor" and "indoor" accelerating aging.
AB  - OBJECTIVES: Optical properties of facial prosthetic elastomers undergo
      significant changes mainly due to aging. The resulting changes in their
      appearance are the main reasons of facial prosthesis' replacement. PURPOSE: The
      purpose of this study was to evaluate changes in the translucency parameter (TP)
      and color (DeltaE*) of polydimethylsiloxane (PDMS) maxillofacial elastomers after
      exposure to 3 different aging conditions (time passage, accelerated "outdoor"
      aging, and accelerated "indoor" aging). MATERIALS AND METHODS: The PDMS
      prosthetic elastomers tested in this study were low- (LTV) and high-temperature
      vulcanized (Episil and Mollomed, respectively) in various shades. Color changes
      (DeltaE*) and translucency parameter (TP) were determined in the CIE L*a*b*
      system using a tristimulus colorimeter. Data were subjected to 2-way analysis of
      variance followed by Tukey post hoc test. In addition, TP values were analyzed by
      paired t tests. The significance level of alpha = 0.05 was set for all tests.
      RESULTS: Translucency parameter values for most samples were significantly
      changed after aging, and DeltaE* values were characterized as unacceptable. Both
      aging procedure and material type affected the changes that occurred. Moreover,
      dark-shaded samples of both silicone materials revealed significant changes in TP
      values before and after aging. DeltaE* was not significantly different among the
      same material samples but had significant differences between the 2 materials
      (Episil and Mollomed). Time passage did not significantly affect TP values
      contrary to the other 2 accelerated aging procedures. Between outdoor and indoor
      aging, no significant differences were detected. CONCLUSIONS: Accelerated outdoor
      and indoor aging caused significant changes in DeltaE* and TP values. Significant
      changes were also detected between material types.

PMID- 21959391
TI  - Tracheobronchial anomalies in syndromic craniosynostosis with 3-dimensional CT
      image and bronchoscopy.
AB  - Patients with syndromic craniosynostosis have many problems involving the upper
      airway, laryngotracheal airway, and tracheobronchial tree. Evaluation of
      tracheobronchial disorders in syndromic craniosynostosis is very important for
      accurately diagnosing these problems. We have used three-dimensional computed
      tomography (CT) imaging of the tracheobronchial tree (three-dimensional tracheal
      CT imaging) since a multidetector CT was installed in our hospital in 2004. In
      this study, we assessed the configuration of the tracheobronchial system using
      three-dimensional tracheal CT imaging and bronchoscopy.During the period from
      2004 to 2009, 48 patients with syndromic craniosynostosis underwent surgery at
      our hospital. Of those, 16 patients required tracheostomy. These syndromic
      craniosynostosis cases were examined with three-dimensional tracheal CT imaging
      and bronchoscopy. All CT scans were performed on a multidetector CT (120 kV, 22
      120 mA, 0.5 s/slice, 1-mm slice; Aquilion; Toshiba Co, Tokyo, Japan) without
      respiratory suppression.All 16 study patients presented with severe stenosis of
      the upper airway on bronchoscopic examination. Seven were confirmed to have
      abnormalities by both bronchoscopy and three-dimensional tracheal CT imaging.
      Four were confirmed to have abnormalities on either bronchoscopy or three
      dimensional tracheal CT imaging, whereas 5 patients were apparently free of
      abnormalities as determined by both modalities.In conclusion, it was possible to
      accurately assess the configuration of the tracheobronchial system using both
      three-dimensional tracheal CT imaging and bronchoscopy. Our results suggest these
      examinations to be very useful for assessing the optimal timing of decannulation
      and respiratory function prognosis.

PMID- 21959392
TI  - Purse-string closure for frontoethmoidal encephalomeningocele.
AB  - BACKGROUND: Skin incision over the nose is routinely made for accessing the nasal
      structures, removing the mass, as well as resecting the redundant skin in
      patients with frontoethmoidal encephalomeningocele (FEEM). Unfortunately, the
      conventional elliptical excision leaves a long, straight-line scar that becomes a
      stigma of the disease. OBJECTIVE: The author describes a purse-string closure
      technique for closure of the skin defect over the nasal dorsum in a patient with
      FEEM, which results in the reduction of a surgical scar. METHODS: The skin
      overlying the encephalocele is pinched and marked around the mass. The skin is
      cut, and the encephalocele is dissected deep down the bony opening. Then a
      bicoronal scalp flap and frontal craniotomy and bilateral medial orbital walls
      osteotomies are performed. The encephalocele is removed at the neck, and the
      dural defect is repaired. The bony defect is repaired and bone-grafted as
      necessary. The skin defect is closed with double layers with the purse-string
      closure technique and crisscross mattress sutures. RESULTS: : Between January
      2004 and July 2009, a total of 7 FEEM patients underwent a 1-stage combined
      intracranial and extracranial repair and reconstruction of the deformity using
      the purse-string closure technique. CONCLUSIONS: The purse-string closure
      technique as described provides an alternative skin closure for the repair and
      reconstruction of FEEM.

PMID- 21959393
TI  - Impact of septoplasty on pulmonary artery pressure in patients with markedly
      deviated septum.
AB  - AIM: The nasal septal deviation (NSD) increases upper airway obstruction. This
      study aimed to measure the mean pulmonary arterial pressure (mPAP) of the
      patients with markedly deviated nasal septum and to determine the effect of
      septoplasty on the pulmonary arterial pressure. METHODS: Fifty-one patients with
      NSD (mean age, 37.1 [SD, 8.6] years; 27 men and 24 women) were included in the
      study. Thirty-five of the patients (22 men, 13 women) aged between 21 and 55
      years (mean, 35.1 [SD, 8.9] years) comprised the control group. Mean pulmonary
      arterial pressure was measured in the preoperative period and postoperative third
      month. RESULTS: The mean preoperative mPAP value (25.4 [SD, 5.3]) of the study
      group was statistically significantly higher than that of the control group (20.5
      [SD, 2.8]) (P = 0.000). There was a significant decrease in mPAP after the
      operation (20.6 [SD, 3.8]) (P = 0.000). Twenty-two of 51 patients had pulmonary
      arterial hypertension. CONCLUSION: Markedly deviated nasal septum significantly
      affected mPAP. Septoplasty was efficient in the treatment of patients with NSD.

PMID- 21959394
TI  - Assessment of the related factors of blood loss and blood ingredients among
      patients under hypotensive anesthesia in orthognathic surgery.
AB  - OBJECTIVE: The objective of the study was to understand the factors associated
      with presurgical and postsurgical blood loss and blood ingredients among patients
      in the treatment of mandibular prognathism by intraoral vertical ramus osteotomy
      combined genioplasty. METHODS: Preoperative and postoperative values of blood
      loss and blood ingredients were collected from 30 mandibular prognathic patients
      who underwent orthognathic surgery. The linear regression models and correlation
      coefficients were used to identify factors with respect to patients' blood loss
      level and 3 types of blood ingredients (ie, red blood cells, hemoglobin, and
      hematocrit). RESULTS: The mean blood loss and operation time were 179.2 mL and
      311.7 minutes, respectively. No blood transfusion was received by our patients.
      After adjusting for potential factors, the regression models showed that no
      significant factor was found to be associated with blood loss and reduce blood
      ingredients. Moreover, female patients were found to be more likely to have a low
      level of presurgical blood ingredients (beta = -0.293 to -3.551; P < 0.05),
      whereas female sex (beta = -1.606 to -4.008; P < 0.001), a high blood loss level
      (beta = -0.003 to -0.009; P < 0.05), and long operation time (beta = -0.005 to 
      0.018; P < 0.05) were associated with a low level of postsurgical blood
      ingredients (ie, hemoglobin and hematocrit). CONCLUSIONS: No significant factor
      was associated with blood loss and reduced blood ingredients among patients in
      orthognathic surgery with hypotenstive anesthesia. Improvements in anesthesia
      provided surgeons with more time to promote hemostasis during surgery.
      Hypotensive anesthesia was a well-accepted method to reduce blood loss during
      orthognathic surgery.

PMID- 21959395
TI  - Impact of different surgery modalities to correct class III jaw deformities on
      the pharyngeal airway space.
AB  - OBJECTIVE: The objective of the study was to compare the outcome of different
      modalities of orthognathic surgery to correct class III jaw deformities
      concerning the pharyngeal airway space, especially in patients with other
      predisposing factors for the development of obstructive sleep apnea. METHODS:
      Lateral cephalograms of 30 Japanese patients (12 males and 18 females, 24.4 [SD,
      6.8] years), who underwent surgical-orthodontic treatment for class III jaw
      deformities, were obtained. Patients were divided into 3 groups: Group A included
      patients who underwent bilateral sagittal split ramus osteotomy; group B patients
      underwent bimaxillary surgery, and group C patients underwent intraoral vertical
      ramus osteotomy. Lateral cephalograms were assessed before surgery and around 3
      months and 1 year after surgery. The paired t-test was used to compare the
      groups, and P < 0.05 was considered significant. RESULTS: In groups A and C who
      underwent sagittal split ramus osteotomy and intraoral vertical ramus osteotomy,
      respectively, the pharyngeal airway was constricted significantly at the 3 levels
      of the pharyngeal airway space on short- and long-term follow-up, whereas in
      group B, who underwent bimaxillary surgery, no significant changes were noted on
      long-term follow-up. CONCLUSIONS: Bimaxillary surgery rather than only mandibular
      setback surgery is preferable to correct class III jaw deformity to prevent
      narrowing of the pharyngeal airway, which might be a predisposing factor in the
      development of obstructive sleep apnea syndrome.

PMID- 21959396
TI  - Changes in the transverse dimensions by vertical ramus osteotomy after mandibular
      prognathism correction.
AB  - OBJECTIVE: A harmonious face displays not only a good lateral profile but also a
      pleasant frontal appearance. The purpose of the current study was to evaluate the
      changes in the transverse dimensions by vertical ramus osteotomy (VRO) in the
      treatment of mandibular prognathism correction. METHODS: Twenty patients who
      underwent mandibular prognathism correction by VRO were included. Lateral and
      frontal cephalometric radiographs were obtained at the following stages:
      preoperative (T1), immediately after the surgery (T2), and completion of
      orthodontic treatment (T3). Three linear measurements (menton, intercondylion,
      and intergonial distances) and the ramus angle were compared from T1 to T3.
      RESULTS: A final mean menton setback of 12.2 mm and upward movement of 0.3 mm
      were noted. The intercondylion and intergonial distances significantly increased
      by 5.1 and 7.1 mm, respectively. Without significant difference, ramus angles
      decreased 1.7 degrees in the right side and 0.1 degrees in the left side.
      CONCLUSION: The surgical correction of mandibular prognathism using VRO led to an
      increase in the transverse dimensions.

PMID- 21959397
TI  - Comprehensive evaluation of three-dimensional philtral morphology.
AB  - This study was designed to evaluate detailed philtral morphology involving sex
      and racial differences and to clarify the objective parameters related to
      subjective judgments regarding the clarity of the philtrum. Fifty-five Japanese
      and 20 Mexican normal subjects aged 24 to 40 years were recruited, and three
      dimensional facial data were acquired using a noncontacting optical surface
      scanner. The visual classification of the philtral column morphology in Japanese
      adults using facial photographs revealed that the predominant philtral column
      shape was different by sex. The three-dimensional anthropometric data showed
      significant sex differences, which were reflected in the more pronounced visual
      impression of the philtrum in men. A comparative study between Japanese and
      Mexican women also revealed certain racial differences. Furthermore, both the
      philtral depth and central angle of Cupid's bow were extracted as explanatory
      variables related to the subjective judgments for the clarity of the philtrum.
      These results suggest that the comprehensive evaluation of philtral morphologic
      features by three-dimensional analysis is a useful means of identifying the ideal
      parameters in philtral construction in cleft surgery.

PMID- 21959398
TI  - Influence of pigment and opacifier on dimensional stability and detail
      reproduction of maxillofacial silicone elastomer.
AB  - We evaluated the influence of chemical disinfection and accelerated aging on the
      dimensional stability and detail reproduction of a silicone elastomer containing
      an opacifier and/or a pigment. A total of 120 samples were fabricated from
      Silastic MDX 4-4210 silicone and divided into groups (n = 10) according to
      pigment and/or opacifier (ceramic powder and/or barium sulfate) and disinfectant
      solution (neutral soap, Efferdent, or 4% chlorhexidine). The specimens were
      disinfected 3 times per week during 60 days and then subjected to accelerated
      aging for 1008 hours. Dimensional stability and detail reproduction tests were
      performed after specimens' fabrication (baseline) and chemical disinfection and
      periodically during accelerated aging (252, 504, and 1008 hours). The results
      were analyzed using 3-way repeated-measures analysis of variance and the Tukey
      Honestly Significant Difference test (a = 0.05). All groups exhibited dimensional
      changes over time. The disinfectant, pigment, and time (P < 0.0001) affected the
      dimensional stability of silicone. Statistically significant dimensional
      differences were not observed between the tested groups. Accelerated aging
      influenced the dimensional stability of the samples. All groups scored 2 in the
      detail reproduction tests, which represents the full reproduction of 3 test
      grooves with accurate angles. Incorporation of opacifier and/or pigment alters
      the dimensional stability of silicones used in facial prosthetics but seems to
      have no influence on detail reproduction. Accelerated aging is responsible for
      most of the dimensional changes in Silastic MDX4 4210, but all dimensional
      changes measured in this study remained within the limits of stability necessary
      for this application.

PMID- 21959399
TI  - Effect of time passage on some physical properties of silicone maxillofacial
      elastomers.
AB  - OBJECTIVES: Changes in color and other physical properties of silicone facial
      prosthesis are the main reasons for its replacement. The purpose of this study
      was to investigate the effect of time passage on some physical properties such as
      tensile strength, modulus of elasticity, elongation at break, tear strength,
      hardness, color stability, and contrast ratio (CR) of 2 silicone facial
      elastomers after being sealed in glass containers and kept in the dark for 1
      year. MATERIALS AND METHODS: Specimens from 2 silicone elastomers (Silasto 30 and
      Premium 2) were made and stored in the dark. Tensile and tear strength tests were
      conducted according to International Organization for Standardization
      specification nos. 37 and 39, respectively, in a universal testing machine. Shore
      A hardness was measured according to the American Society for Testing Materials
      specification D 2240. Color changes (DeltaEpsilon*) were determined in the CIE
      L*a*b* system using a tristimulus colorimeter, and CR also was calculated. Data
      were analyzed by paired and unpaired t-tests at a significance level of alpha =
      0.05. RESULTS: Elongation at break, modulus of elasticity, and hardness were
      significantly changed, whereas changes in CR were observed only in 1 of the 2
      elastomers. Tensile and tear strengths were not significantly changed for both of
      them. Within the limitations of this study, color changes (DeltaEpsilon) were
      unacceptable. CONCLUSIONS: Most of the physical properties studied were
      significantly affected because of time passage. Mechanical and physical
      properties of silicone maxillofacial elastomers can be changed with time passage
      (natural aging in the dark). The average time of replacing a facial prostheses is
      6 to 18 months; thus, it is important that the findings of this study covered a
      period of 12 months. Time passage seems to be a critical factor contributing to
      the overall deterioration of a silicone maxillofacial elastomer.

PMID- 21959400
TI  - Measuring progressive soft tissue change with nasoalveolar molding using a three
      dimensional system.
AB  - BACKGROUND: For craniofacial orthodontics and surgery to progress, accurate
      temporal evaluation of soft tissue and skeletal change with treatment is
      necessary. Evolution in three-dimensional imaging eliminates certain inherent
      challenges in making such measurements in infants with facial clefts. OBJECTIVE:
      The aim of this pilot study was to measure progressive three-dimensional changes
      in nasal form in a series of infants with facial clefts during the course of
      presurgical nasoalveolar molding. MATERIALS AND METHODS: In 5 infants with
      unrepaired cleft lip and palate, three-dimensional photographs were obtained
      using the 3dMD system (3dMD, Inc, Atlanta, GA) at 2-week intervals during
      nasoalveolar molding treatment. Using the 3dMD Vultus software, temporal soft
      tissue changes were evaluated quantitatively based on three-dimensional linear
      measurements of 3 landmarks in the nasal area and qualitative changes in the
      surface shell. RESULTS: Increase in columellar length on the cleft side and
      decrease of the nostril floor on the noncleft side were observed in all subjects.
      Progressive changes were observed most significantly in week 4 (T3) into
      treatment. CONCLUSIONS: This pilot study describes an approach using the 3dMD
      photo system with Vultus software for measuring the progressive change in the
      nasal soft tissues. The 3dMD system was believed to be valuable for facial
      analysis in this setting.

PMID- 21959401
TI  - Effects of transsylvian-transinsular approach to hypertensive putaminal hematoma
      operation and electroacupuncture on motor recovery.
AB  - OBJECTIVE: In this study, a comparison of motor recovery on hypertensive
      putaminal hematoma (HPH) with 30 mL or more has been made between conventional
      treatment and decompressive craniectomy (DC) combined with electroacupuncture
      (EA). This study aims to examine whether transsylvian-transinsular approach (TTA)
      to HPH evacuation, DC, and EA have additional value to post-cerebral hemorrhage
      motor rehabilitation. METHODS: One hundred twenty patients with HPH of 30-mL
      volume or greater, who were admitted within 6 hours after ictus, were included in
      this study. Of the 120 patients, 80 were operated on for hematoma evacuation DC
      through TTA. The postoperative patients were divided into combined therapy group
      (CTG) and operation with exercises group (OEG). Combined therapy group (n = 40)
      was treated with EA, functional exercises from 1 to 3 days after hematoma
      evacuation DC through TTA, twice each day, and OEG (n = 40) accepted only the
      same operation and functional exercises. Another 40 patients were classified as
      functional exercises group to be treated conservatively and with functional
      exercises only after their relatives declined authorization for surgery and EA.
      The habilitation effects were assessed by blinded assessors at weeks 0 and 8.
      Outcome measures included Fugl-Meyer assessment, Barthel Index, and Functional
      Independence Measure. RESULTS: The statistical difference on the motor recovery
      was considerable (P < 0.05) between CTG and OEG. Significant differences were
      observed between CTG and physical therapy group (P < 0.01), and we also found
      statistical difference (P < 0.05) between OEG and functional exercises group.
      Surgically treated patients received significantly better motor recovery than did
      the conservatively treated patients. CONCLUSIONS: Microsurgical treatment via TTA
      of HPH and postoperative EA at an early stage result in improved outcome of motor
      recovery. Transsylvian-transinsular approach for HPH operation and postoperative
      EA at an early stage are advocated.

PMID- 21959402
TI  - Analysis of mandibular fractures.
AB  - We investigated the etiology, incidence, and complications of patients with
      mandibular fracture in Amsterdam for a period of 10 years. Between January 2000
      and January 2009, 213 patients with surgically treated mandibular fracture were
      identified. Two hundred thirteen patients were included with a mean age of 32.5
      (SD, 15.2) years. Male-female ratio was 2.2:1. A total of 410 fracture lines were
      identified. In violence-related injuries, angle fractures were proved to be the
      main fracture site. For male patients, violence (33.6%) was the main cause of
      injury. The most common cause for female patients was traffic related. In 169
      patients, open reduction with internal fixation was performed in 17 patients
      without intermaxillary fixation. Twenty-seven patients were treated only with
      intermaxillary fixation. A total of 1738 screws and 393 plates were used. Sixty
      patients presented with complications. The results of this report are partly in
      line with other studies and provides important data for the design of plans for
      injury prevention.

PMID- 21959403
TI  - Effects of irradiation on growth and differentiation-related gene expression in
      osteoblasts.
AB  - Osteoblasts are bone-forming cells that are responsible for the production of
      bone extracellular matrix. Osteoradionecrosis is a complication of radiation
      therapy for carcinoma of the head and neck that occurs in 3% to 8.2% of
      irradiated patients. The irradiation effect on osteoblast differentiation has not
      been fully elucidated. The objective of our research was to elucidate the effects
      of radiation on the growth and differentiation-related gene expression in
      osteoblast in vitro. Three differentiation-related genes, alkaline phosphatase,
      type I collagen, and osteocalcin, were tested in our experiment. The results
      showed that radiation inhibited the proliferation of the osteoblasts in a dose
      dependent manner and induced G2/M cell cycle arrest. Irradiation, 4 and 8 Gy,
      enhanced the differentiation-related gene expression of MC3T3-E1 cells 7 days
      after irradiation. However, the differentiation-related gene expression was
      decreased 21 days after irradiation in the 4- and 8-Gy groups. This work presents
      the dynamic phenotypic expression changes of osteoblastic cells after x-ray
      irradiation.

PMID- 21959404
TI  - Forces charging the orbital floor after fractures.
AB  - The objective of this study was first to establish a method to measure forces and
      displacement of the orbital content in defects of the orbital floor in truncated
      fresh and unfixed heads and second to characterize reconstruction materials with
      regard to punctuation strength and compression.Orbital floor defects (10 * 20 mm
      and 15 * 20 mm; 3 mm behind the orbital rim) were prepared after Le Fort I
      osteotomy. The values of force and displacement were recorded in 6 freshly frozen
      human heads. In addition, the punctuation strength of 2 reconstruction materials
      (polydioxanone [PDS] foil and collagen membrane) was evaluated using a Zwick Z010
      TN1 universal testing machine. The forces of the orbital content (28.41 [SD, 1.6]
      g) applied to the defects of 10 * 20 mm and 15 * 20 mm with an intact periorbita
      were 0.04 (SD, 0.003) N (0.0002 MPa) and 0.07 (SD, 0.02) N (0.0002 MPa),
      respectively, and with a split periorbita were 0.06 (SD, 0.03) N (0.0003 MPa) and
      0.08 (SD, 0.06) N (0.00026 MPa), respectively. The displacement values without
      reconstruction materials of the 10 * 20-mm and 15 * 20-mm defects were 0.94 (SD,
      0.7) mm and 1.2 (SD, 0.5) mm, respectively. The PDS foil could withstand forces
      of 118.9 (SD, 14.1) N (0.375 MPa), and the collagen membrane could withstand
      forces of 44.5 (SD, 5.3) N (0.14 MPa). This is the first study to report forces
      charging the orbital floor. The presented results support the use of PDS foils
      and collagen membranes as reconstruction materials for orbital floor defects, at
      least in smaller and medium-sized fractures.

PMID- 21959405
TI  - Nasometric and aerodynamic outcome analysis of pharyngeal flap surgery for the
      management of velopharyngeal insufficiency.
AB  - OBJECTIVE: This study aimed to evaluate the effectiveness of pharyngeal flap
      surgery (PFS) for the management of velopharyngeal insufficiency in cleft
      lip/palate patients and to assess the impact of age at surgery, surgeon's skills,
      and postoperative speech therapy on the outcomes. METHODS: Prospective
      preoperative and postoperative assessments were performed on 240 patients aged 6
      to 57 years using nasometry and pressure-flow studies.This study was carried out
      in a quaternary hospital.This study was superiorly based on PFS.Speech nasalance
      scores were assessed by nasometry and velopharyngeal orifice area assessed by
      pressure-flow technique, 2 days before and 1 year after PFS, on average.
      Differences were considered significant when P < 0.05. RESULTS: Significant
      reduction in nasalance scores was observed in 68% of the cases, and improvement
      of velopharyngeal area was observed in 66%. Rates of 55% and 48%, respectively,
      were observed when complete resolution was considered. Higher success rates were
      observed in children (81%) compared with other age groups analyzed and in
      patients who had concluded postoperative speech therapy (86%). Results did not
      differ among surgeons. CONCLUSIONS: Pharyngeal flap surgery was shown to be
      effective in reducing nasalance scores and velopharyngeal area during speech for
      a significant number of patients. Complete resolution was observed in smaller
      number of cases. Age at surgery and postoperative speech therapy were relevant
      factors for treatment success.

PMID- 21959406
TI  - Immunohistochemical comparison of the expression of p53 and MDM2 proteins in
      ameloblastomas and keratocystic odontogenic tumors.
AB  - OBJECTIVE: Ameloblastoma and keratocystic odontogenic tumor (KOT) is
      characterized by a benign but locally invasive behavior with a high risk of
      recurrence. MDM2 (murine double minute 2), an amplifier of cell proliferation,
      and p53, a tumor suppressor gene, are overexpressed in some odontogenic lesions.
      The aim of this study was to compare the expression of MDM2 and p53 in
      ameloblastoma and KOT as 2 lesions with similar biologic behavior, by
      immunohistochemistry. METHODS: The expressions of MDM2 and p53 proteins were
      determined in 39 ameloblastomas (15 follicular types, 15 plexiform types, and 9
      unicystic types) and 15 KOTs. RESULTS: P53 protein was expressed in 100% of KOTs
      and 77.8% of ameloblastomas, and MDM2 was detected in 74.8% of ameloblastomas and
      80% of KOTs. There was no statistical difference between MDM2 and p53 expressions
      in different subtypes of ameloblastomas and also when KOTs were compared with
      them (P > 0.05). There was a significant difference between immunohistochemical
      reactivity of MDM2 among subtypes of ameloblastomas (P < 0.05). MDM2 and p53
      expressions were positively correlated. CONCLUSIONS: Overexpression of p53 and
      MDM2 is associated with the pathogenesis and oncogenesis of ameloblastomas and
      KOT. Overexpression of these markers can contribute to similar biologic behavior
      of these lesions.

PMID- 21959407
TI  - Ewing sarcoma of the jaws.
AB  - Three cases of Ewing sarcoma in the jaw bones are presented. The first patient is
      a 43-year-old woman with a rapidly growing tumor in the hard palate. The second
      patient is a 9-year-old girl with tumor in the left mandibular ramus and body. In
      both patients, the tumors were excised with significant safe margins. However,
      postoperative histopathologic evaluation revealed the presence of tumor cells in
      bony margins, necessitating a second surgery. The third patient is a 9-year-old
      boy with tumor in the right mandibular ramus and body. In patients 1 and 2,
      chemotherapy failed to control the tumor; however, in patient 3, chemotherapy
      resulted in significant shrinkage of the tumor and no further growth.

PMID- 21959408
TI  - Influence of different base thicknesses on maxillary complete denture processing:
      linear and angular graphic analysis on the movement of artificial teeth.
AB  - OBJECTIVE: The purpose of this study was to compare the dental movement that
      occurs during the processing of maxillary complete dentures with 3 different base
      thicknesses, using 2 investment methods, and microwave polymerization. METHODS: A
      sample of 42 denture models was randomly divided into 6 groups (n = 7), with base
      thicknesses of 1.25, 2.50, and 3.75 mm and gypsum or silicone flask investment.
      Points were demarcated on the distal surface of the second molars and on the back
      of the gypsum cast at the alveolar ridge level to allow linear and angular
      measurement using AutoCAD software. The data were subjected to analysis of
      variance with double factor, Tukey test and Fisher (post hoc). RESULTS: Angular
      analysis of the varying methods and their interactions generated a statistical
      difference (P = 0.023) when the magnitudes of molar inclination were compared.
      Tooth movement was greater for thin-based prostheses, 1.25 mm (-0.234), versus
      thick 3.75 mm (0.2395), with antagonistic behavior. Prosthesis investment with
      silicone (0.053) showed greater vertical change compared with the gypsum
      investment (0.032). There was a difference between the point of analysis,
      demonstrating that the changes were not symmetric. CONCLUSIONS: All groups
      evaluated showed change in the position of artificial teeth after processing. The
      complete denture with a thin base (1.25 mm) and silicone investment showed the
      worst results, whereas intermediate thickness (2.50 mm) was demonstrated to be
      ideal for the denture base.

PMID- 21959409
TI  - Viability of cartilage grafts in various forms.
AB  - The viability of cartilage grafts, in many forms, has been researched since the
      using of cartilage grafts in surgical procedures. Cryopreservation period and
      viability of cartilage grafts have remained unclear. This study was performed to
      investigate the durability, viability, and behavior of fresh or cryopreserved
      cartilage grafts when used as autografts or allografts in various forms.Six
      cartilage grafts (1 of each preparation type; 3 blocks and 3 diced) were prepared
      by wrapping with Surgicel or autogenous fascia, or they were left bare. After the
      graft preparation stage, the cartilage grafts were inserted into pockets prepared
      on the dorsum of each rabbit. Groups 1, 2, 3, and 4 (6 rabbits in each group)
      received autogenous fresh grafts, allogenous fresh grafts, autogenous
      cryopreserved grafts, and allogenous cryopreserved grafts, respectively. All
      cartilage grafts were implanted for 2 months.At the end of the second month,
      specimens were harvested and analyzed. The bare grafts provided the most viable
      specimens. There was no significant difference between the frozen or fresh and
      allograft or autograft groups with respect to viability and resorption ratios.
      The bare block graft, in all groups, survived significantly more than the other
      graft types.Allografts (homografts), similar autografts, did not create major
      problems, and they had excellent host tolerance and low antigenicity, especially
      when the perichondrium was removed. Viability and durability of the bare grafts
      (diced and block) were better than fascia or Surgicel-wrapped cartilage graft
      forms.

PMID- 21959410
TI  - Total maxillary swing approach to the skull base for advanced intracranial and
      extracranial nasopharyngeal angiofibroma.
AB  - The main objective of surgical approaches to the anterior and anterolateral skull
      base is to have maximum exposure so injury to important structures is avoided,
      and surgical complications are reduced. At our institution, we used total
      maxillary swing (TMS) to approach the anterior and anterolateral skull base for
      resection of both malignant and benign tumors. We modified some of the techniques
      described in TMS to avoid complications encountered previously. The purpose of
      this article was to present the usefulness of TMS for maximum exposure of the
      anterior and anterolateral skull base using advanced nasopharyngeal angiofibroma
      (NPA) as the reference disease.We retrospectively reviewed 16 patients who
      underwent excision of NPA by TMS from 2005 to May 2011. The operative techniques,
      operative findings, postoperative complications, and follow-up records were
      reviewed and analyzed.Of the 16 cases of NPA, 5 had intracranial extensions. All
      had lateral extensions to the pterygopalatine fossa. The pterygoid base was
      explored in all cases. In 10 cases, the tumors were present in the spongy bone of
      the pterygoid bases, whereas in 6 cases, the base of the pterygoids was eroded
      and floating. In all cases, the tumor was completely removed. Complications
      encountered previously were avoided by the modifications to TMS. Complications
      encountered because of extensiveness of the tumor were easily managed. No
      patients had any recurrence until now.Total maxillary swing provides maximum
      exposure to the anterior and anterolateral skull base for complete removal of the
      tumors in those areas with minimal complications.

PMID- 21959411
TI  - Osteoradionecrosis of the skull after radiation therapy for invasive carcinoma.
AB  - Osteoradionecrosis (ORN) of the skull is a rare but fatal complication of
      radiation therapy for the treatment of head and neck malignancies. The
      pathogenesis of ORN follows the "3Hs Theory" proposed by Marx (J Oral Maxillofac
      Surg 1983;41:283-288) in which radiation induces tissue injury by causing vessel
      thrombosis (hypovascularity), which leads to hypoxia, and results in cell death
      of the skin and the underlying structure of the bony element (hypocellularity)
      including the deep visceral structures. This note details a patient with severe
      and extensive ORN of the parietooccipital region of the skull because of a large
      dose of radiation therapy for the treatment of an invasive basal cell carcinoma
      of the scalp. The patient's condition was further complicated by an extensive
      infection with methicillin-resistant Staphylococcus aureus, which leads to
      meningitis and cerebral edema as well as cerebritis. The patient was successfully
      treated with interdisciplinary medical and surgical aggressive therapy and
      radical procedures involving 4 separate trips to the operating room for an 18
      month period. Success was achieved because of early clinical diagnosis of ORN,
      aggressive eradication of infected and necrotic tissues including the brain, and
      restoration of functioning and viable tissues through the use of local flaps to
      change an open wound to a closed wound.

PMID- 21959412
TI  - Fixed drug eruption against rupatadine fumarate.
AB  - Second generation of antihistaminics have better therapeutic efficacy and more
      predictable pharmacological responses at lower doses than older compounds.
      However, new compounds have a reduced adverse reaction profile; clinicians can
      also encounter some unexpected adverse effects of these newer compounds. We
      report the first case of fixed drug eruption of rupatadine fumarate, which was
      confirmed by oral provocation test.

PMID- 21959413
TI  - Comparison between lipofilling and a nonabsorbable filler for facial wasting
      rehabilitation in HIV-positive patients.
AB  - BACKGROUND: Several treatments have been described for facial wasting
      rehabilitation in HIV-positive patients. In this article, we compare lipofilling
      and a nonabsorbable filler for facial wasting rehabilitation induced by
      antiretroviral therapy in HIV-positive patients. METHODS: This study was
      conducted as a clinical prospective study. Twenty-three HIV-positive patients
      affected by facial wasting were treated for facial rehabilitation, between
      January 2007 and December 2008, at the Head and Neck Department of the II
      University of Naples. They were divided into 2 groups; the first group was
      treated with lipofilling (group A), and the second one with the injection of a
      nonabsorbable filler, Aquamid reconstruction (Contura International A/S, Soeborg,
      Denmark) (group B).All the patients were HIV-positive, they had been receiving
      antiretroviral therapy for several years (1.8-6.7 years, 3.2 years on average)
      and showed clinical signs of facial lipoatrophy. Group A was composed of 14
      patients (9 men, 5 women; mean age, 43.7 years), all presenting facial wasting
      and lipohypertrophied areas of the body. Group B was composed of 9 male patients,
      7 presenting only facial wasting, and 2 presenting lipohypertrophied areas of the
      body (mean age, 44.8 years). Clinical efficacy was assessed independently by the
      investigator and the patient, 3 months, 6 months, and 1 year after baseline. The
      main assessment was made by the investigator using the Global Aesthetic
      Improvement Scale (GAIS) 1 year after baseline; secondary assessment using the
      GAIS was made by the investigator and the patient 6 months after baseline.
      RESULTS: There were no major complications. No infections or other complications
      were observed. According to GAIS ratings, group A (lipofilling) obtained
      significantly higher ratings than did group B (nonabsorbable filler) after
      baseline (P < 0.05). CONCLUSIONS: We can treat HIV-related lipodistrophy more
      extensively with lipofilling because, after harvesting the fat graft, other body
      contouring procedures also can be performed; there is a better aesthetic outcome
      in facial rehabilitation performed with lipofilling, probably due to the
      possibility to fill deeper than with nonabsorbable fillers.

PMID- 21959415
TI  - Structural fat grafting: facial volumetric restoration in complex reconstructive
      surgery.
AB  - BACKGROUND: The authors overview the application of structural fat grafting (SFG)
      in the management of volumetric deficit in the maxillofacial area. Structural fat
      grafting was introduced as a way to improve facial aesthetics and in recent years
      has evolved into applications in craniomaxillofacial reconstructive surgery.
      METHODS: A retrospective cohort study population was composed of patients grafted
      with autologous fat referred to our department from February 2005 to July 2009.
      Each patient was operated on with SFG technique according to Coleman. Subjects
      were screened to these possessing an atrophy of facial soft tissues after trauma,
      tumor resection, congenital deformities and clefts, Parry-Romberg and
      scleroderma, orbital and periorbital surgery, facial palsy, burns, and scars.
      RESULTS: Forty-seven patients (27 females and 20 males) with a mean age of 38
      years (minimum, 15 years; maximum, 71 years) were enrolled in the current study.
      The mean postoperative follow-up was 14 months. A total of 548 sites were grafted
      into 47 patients: malar, n = 103; nasolabial fold, n = 82; lip, n = 86; eyebrow,
      n = 32; jaw line, n = 18; philtrum, n = 19; forehead, n = 33; temple, n = 34;
      eyelid, n = 70; chin, n = 16; cheek, n = 25; nose, n = 23; and neck scar, n = 7.
      Each patient was operated on 1.6 times, and 11.6 was the average number of
      grafted sites. CONCLUSIONS: The authors have performed 548 procedures of SFG in
      47 patients with good results as well as improvement in facial morphology,
      function, shape, and volume and improvement in the patients' appearance.

PMID- 21959416
TI  - Long-term evaluation of maxillary reconstruction by iliac bone graft.
AB  - The aim of this study was to analyze histologic and immunohistochemical
      modifications taking place in maxillary sites reconstructed by iliac crest bone
      grafts, 4 months (T1) and 10 years (T2) after grafting, in comparison to native
      iliac crest bone (T0).By light microscopy, T1 samples showed well-organized
      osteoblasts and extracellular matrix (ECM), and surrounding areas of connective
      tissue where a discrete number of blood vessels can be distinguished. Samples
      obtained from reconstructed areas after a long period of follow-up (T2) were
      characterized by uniform mineralized ECM with cavities containing osteocytes,
      whereas T0 samples disclosed both mineralized matrix and bone marrow. Matrix
      metalloproteinase 2 (MMP-2), vascular endothelial growth factor (VEGF), inducible
      nitric oxide synthase (iNOS), and bone sialoprotein (BSP) expressions were
      investigated by immunohistochemical analysis. Both MMP-2 and VEGF showed
      significantly increased expression in T1, with respect to T0, and lowered in T2.
      Otherwise, BSP expression, which was elevated in native iliac crest bone (T0),
      was deeply decreased in T1 and T2 samples. Moreover, changes in iNOS expression
      and in apoptotic cell nuclei percentages (TUNEL analysis) seemed to have a
      similar trend, increasing in T1 and lowering in T2.After a period of 4 months,
      iliac crest bone graft-reconstructed sites show mineralizing nuclei not strongly
      represented, as suggested by BSP lower expression, whereas new blood vessel
      proliferation and active remodeling phenomena are developing. After a long period
      from the grafting (T2), BSP expression decreases along with MMP-2, VEGF, and
      iNOS, suggesting the presence of only weak arrangement phenomena of the graft.

PMID- 21959414
TI  - Occurrence of odontogenic infections in patients treated in a postgraduation
      program on maxillofacial surgery and traumatology.
AB  - This study assessed the occurrence and characteristics of oral and maxillofacial
      infections in patients treated at a Brazilian oral and maxillofacial emergency
      service during a 7-year period. The clinical files of all patients treated at the
      Oral and Maxillofacial Surgery and Traumatology Service of the Aracatuba Dental
      School, Sao Paulo State University, Brazil, between 2002 and 2008 were reviewed.
      From a population of 3645 patients treated in this period, the study sample
      consisted of 93 subjects who presented odontogenic infections. Data referring to
      the patients' sex, age, medical history, and the etiology, diagnosis,
      complications, drug therapy/treatment, and evolution of the pathologic diseases
      were collected and analyzed using the Epi Info 2000 software. Of these patients,
      54 were men (58.1%) and 39 were women (41.9%). Most patients were in the 31- to
      40-year-old (20.7%) and 21- to 30-year-old (19.6%) age groups. The most frequent
      etiology was pulp necrosis due to caries (80.6%). Regarding the treatment,
      antibiotics were administered to all patients, surgical drainage was done in 75
      patients (82.4%), and 44 patients (47.3%) needed hospital admission. First
      generation cephalosporin alone or combined with other drugs was the most
      prescribed antibiotic (n = 26) followed by penicillin G (n = 25). Most patients
      (n = 85, 91.4%) responded well to the treatment. Five cases had complications: 3
      patients needed hospital readmission, 1 case progressed to descending
      mediastinitis, and 1 patient died. Odontogenic infections can be life-threatening
      and require hospital admission for adequate patient care. Complications from
      odontogenic infections, although rare, may be fatal if not properly managed.

PMID- 21959417
TI  - Establishing the customized occlusal plane in systemized surgical treatment
      objectives of class III.
AB  - The purpose of this study was to present a new approach for establishing the
      customized occlusal plane for an individual patient in systemized surgical
      treatment objective of class III cases. After the correction of incisor
      inclination to occlusal planes (U1-MxOP and L1-MnOP), the intermaxillary
      relationship can be established with normal overbite/overjet and maximum
      intercuspation. The anterior limits of the maxilla and the mandible can be
      positioned according to A to N perpendicular, Frankfort horizontal (FH) to AB
      plane angle, and upper incisor display. The vertical level of the upper first
      molar can then be determined in relation to the Y plane (an imaginary arch drawn
      using the distance between the lower incisor edge point and the rotation center
      point of the condylar head as a radius) and a triangle projected by the upper and
      lower limits of the FH to the occlusal plane (FH-OP triangle). Soft-tissue facial
      balance can be checked with the lip/chin projection in relation to the true
      vertical line at subnasale and the lower third facial height ratio. Appropriate
      superior impaction of the posterior part of the maxilla in relation to the Y
      plane and FH-OP triangle in case 1 produced significant improvement of the facial
      profile and occlusion. However, case 2 showed that the amount of superior
      impaction of the posterior part of the maxilla was not enough to produce a
      significant setback of the mandible and retraction of the lip and chin. The
      systemized surgical treatment objective flowchart that could set the customized
      occlusal plane for an individual patient might provide a useful guideline for
      obtaining optimal aesthetics and functional occlusion in class III cases.

PMID- 21959418
TI  - One-step transversal palatal distraction and maxillary repositioning: technical
      considerations, advantages, and long-term stability.
AB  - BACKGROUND: Transversal maxillary hypoplasia in adolescence is a frequently seen
      pathology, which can be treated with a combination of surgery and orthodontic
      treatment to widen the maxilla in skeletally matured patients.We evaluated the
      advantages of a new surgical technique: Le Fort I distraction osteogenesis using
      a bone-borne device. Because relapse is one of the main problems in surgical
      maxillary expansion, long-term stability of this new technique was evaluated.
      METHODS: Data from 4 adult patients with maxillary restriction, class III
      malocclusion, or maxillary malposition were collected preoperatively, 4 months
      after distraction, and 5 years after distraction. Measurements were recorded on
      dental models to detect palatal expansion at dental level; cephalograms by
      lateral and posteroanterior plane were analyzed to detect maxillary movements.
      RESULTS: Maxillary measurements were substantially stable 5 years after
      distractions. Only minor dental movements occurred at the dental analysis after 5
      years related to a lack of orthodontic contention without any compromise of the
      dental result (no crossbite relapse and class I stability). CONCLUSIONS: Le Fort
      I with down-fracture for expansion and repositioning by bone-borne distractor
      device can [corrected] be used to simultaneously widen, advance, and vertically
      reposition the maxilla without causing healing problems, particularly using a
      rigid distraction device. Long-term stability can be achieved; however, further
      studies with a larger number of patients will be necessary for better evaluation.

PMID- 21959419
TI  - Endonasal endoscopic approach for the resection of chondroid chordoma with skull
      base involvement.
AB  - Chordoma is an uncommon tumor of bone that is believed to develop from remnants
      of the notochord. The chondroid variant of chordomas contains elements possessing
      both chordoma and cartilaginous tissues. Chondroid chordomas occur almost
      exclusively in the sphenooccipital region of the skull base. Primary treatment
      with surgical excision and radiotherapy for residual or recurrent tumor is
      recommended. Here, we describe a patient with chondroid chordoma with skull base
      involvement who underwent an expanded endonasal endoscopic approach for complete
      resection. In conclusion, endonasal endoscopic approach should be kept in mind
      for the resection of carefully selected chondroid chordomas with skull base
      involvement because of its minimally invasive characteristics.

PMID- 21959420
TI  - Genetics of syndromic and nonsyndromic cleft lip and palate.
AB  - Cleft of the lip with or without cleft palate (CL/P) represents one of the
      commonest congenital malformations in Western countries. Based on their
      association with specific malformative patterns or their presence as isolated
      defects, CL/P can be classified as syndromic and nonsyndromic, respectively. Both
      forms of CL/P are characterized by a strong genetic component. Syndromic forms
      are in many cases due to chromosomal aberrations or monogenic diseases. Among
      these, the Van der Woude syndrome, caused by mutation of the IRF6 gene,
      represents the commonest form of syndromic CL/P, accounting for about 2% of all
      cases. On the other hand, nonsyndromic CL/P is a multifactorial disease derived
      by the interaction between genetic and environmental factors. In recent years,
      great efforts have been made to identify the genes involved in the susceptibility
      to nonsyndromic CL/P and to disclose their relationship with specific
      environmental risk factors, to get information about the pathogenic mechanism
      leading to the malformation. In this article, we will review the most recent
      findings about the genes involved in the pathogenesis of syndromic and
      nonsyndromic CL/P, to provide information about the opportunity in the future to
      use specific genetic testing for the identification of at-risk mothers and the
      prevention of the disease based on a personalized approach.

PMID- 21959421
TI  - Nonvascularized bone grafting for mandibular reconstruction: myth or reality?
AB  - This retrospective study analyzes the long-term results and complications of
      mandibular reconstruction with nonvascularized bone grafts (NVBGs) and suggests
      refinements. A total of 166 patients underwent mandibular ablation and primary
      reconstruction between June 1990 and August 2009, of which 101 were NVBGs, 27
      were vascularized bone grafts, and 38 were with functional plate reconstruction.
      Eighty-seven of 101 patients undergoing NVBG, having all records and followed up
      for a minimum of 12 months, were included in this study. The analysis criteria
      included site of defect, surgical approach, method of graft fixation, bony
      continuity and stability, presence or absence of infection, aesthetic and
      functional prosthetic rehabilitation, donor-site morbidity, and clinical and
      radiological changes in the reconstructed area.The overall success with NVBGs in
      our study was 77 (88.5%) of 87. We used ilium in 68 cases (78.16%), fibula in 16
      cases (18.39%), and rib in 3 cases (3.44%). Ten cases (11.5%) showed complete
      failure due to infection (7 cases) and resorption (3 cases).Nonvascularized bone
      grafts could be used judiciously for reconstruction of selective mandibular
      resection defects where there is not much of soft tissue loss, or where 2-layer
      watertight closure can be achieved intraorally and extraorally. Where only a
      single-layer intraoral closure is anticipated, either additional soft tissue
      should be brought submucosally or there should not be extraoral-intraoral
      communication even during surgery. Also precise patient selection, surgical
      planning, and execution with meticulous nursing care are keys to success.

PMID- 21959423
TI  - Syndromic craniosynostosis in a modern-age skeleton from Siena, Italy.
AB  - The skeleton of a female adult found in archaeological excavations carried out in
      Siena (central Italy) and dated back to the modern age showed a severe skull
      malformation due to the premature bilateral closure of the coronal suture, which
      determined a deformed brachycephalic skull. This craniosynostosis was associated
      with other malformations, such as shallow orbits, hypertelorism, mandibular
      prognathism, and consequent malocclusion, but there was absence of anomalies in
      the remaining bones of the extremities. These features did not seem to be related
      to an isolated condition but to a more complex genetic syndrome, suggesting a
      possible case of Crouzon syndrome. Besides representing a rare finding in
      archaeological material, the present case provides the opportunity to observe in
      an adult subject lesions typical of this congenital disorder, which is at present
      surgically corrected in infantile age.

PMID- 21959422
TI  - Speech outcomes and velopharyngeal function after surgical treatment of
      velopharyngeal insufficiency in individuals with signs of velocardiofacial
      syndrome.
AB  - OBJECTIVE: The objective of the study was to analyze if individuals with
      velocardiofacial syndrome (VCFS) present the same characteristics of speech and
      velopharyngeal function (VPF) compared with patients with nonsyndromic submucous
      cleft palate, as well as to compare the effectiveness of palate surgery on the
      speech function and VPF between groups. METHODS: This was a prospective study
      performed at the Speech Therapy Sector and Physiology Laboratory, Hospital for
      Rehabilitation of Craniofacial Anomalies/University of Sao Paulo.The procedure
      performed was primary palatoplasty associated or not to superiorly based
      pharyngeal flap surgery.There were 50 patients with velopharyngeal insufficiency:
      25 with signals of VCFS (VCFS group) and 25 without syndrome with submucous cleft
      palate (SMCP group).The hypernasality was scored by 3 examiners; nasalance was
      evaluated by nasometry, and VPF was assessed by the size of the velopharyngeal
      gap on the nasoendoscopy. The evaluations were conducted before and, in average,
      18 months after surgery. RESULTS: Before surgery, the VCFS and SMCP groups
      presented similar speech function and VPF characteristics in all parameters, with
      no statistically significant differences. After surgery, there was reduction in
      the hypernasality, nasalance, and VPF in, respectively, 20%, 31%, and 36% of
      patients in the VCFS group and in 24%, 30%, and 30% in the SMCP group.
      Elimination/normalization of variables was obtained in 28%, 19%, and 8% of
      patients in the VCFS group and 20%, 40%, and 25% in the SMCP group, respectively,
      for hypernasality, nasalance, and VPF. There was no statistically significant
      difference between groups. CONCLUSIONS: Patients with VCFS presented similar
      speech function and VPF characteristics as patients with nonsyndromic SMCP. The
      surgery for velopharyngeal insufficiency correction was equally effective for the
      improvement and resolution of speech symptoms and VPF in patients with VCFS
      compared with the SMCP group.

PMID- 21959424
TI  - Conservative treatment of severe limited mouth opening after transtemporal
      craniotomy.
AB  - Limited mouth opening (LMO) is a common complication of the transtemporal
      craniotomy that is often involved in the temporalis and temporomandibular joint.
      The occurrence of prolonged LMO was rare. Risk factors for such limitation after
      these neurosurgical procedures are defined, and the strategies of treatment and
      prevention are further discussed.This article presents 12 patients with severe
      LMO after transtemporal neurosurgical procedures. Four patients received
      myofunctional training combined with the neuromuscular blocking in the
      temporalis, which methods may be more effective for LMO within 3 months. Five
      patients received myofunctional training combined with joint injection of
      hyaluronic acid, which methods may be more effective for LMO beyond 3 months. In
      addition, 2 patients who experienced LMO for more than 1 year had to receive
      coronoidectomy.Therefore, these conservative treatments have proved a useful
      method to restore LMO at an early stage. If intervention and diagnosis was
      delayed, the efficiency of these conservative therapies would decline, and
      coronoidectomy has to be considered. The early physiotherapy cannot be
      overemphasized to minimize this complication after these transtemporal
      neurosurgical procedures.

PMID- 21959425
TI  - Posterolateral skull base reconstruction using the supraclavicular artery island
      flap.
AB  - The supraclavicular artery island (SAI) flap is a viable fasciocutaneous option
      for the reconstruction of head and neck defects. Although authors have reported
      success using SAI flaps for various reconstructive indications, concerns of a
      tenuous blood supply and distal ischemia have previously limited its use in the
      posterolateral skull base. This case series reports the outcomes of 5 consecutive
      patients receiving SAI flaps for posterolateral skull base reconstruction. All
      flaps were harvested in less than 1 hour with primary closure of all donor sites.
      A single patient developed superficial necrosis of the distal flap, which was
      repaired with a full-thickness skin graft. There were no other complications, and
      no donor site morbidity was observed. The SAI flap is an excellent option for the
      reconstruction of posterolateral skull base defects. The close color match, easy
      harvest within 1 hour, lack of microsurgical anastomosis, and absence of donor
      site morbidity support its continued utilization.

PMID- 21959426
TI  - Correlation between bone density and angular deviation of implants placed using
      CT-generated surgical guides.
AB  - BACKGROUND: The aim of this study was to evaluate the correlation between the
      density of bone where implants were placed and the angular deviations that
      occurred between the virtually planned and actually placed implants using 2
      different stereolithographic surgical guides. METHODS: The study population
      consisted of 54 patients who received 216 implants. Computed tomography machine
      was used for preoperative evaluation of the jawbone for implant therapy as well
      as determination of the bone density values (Hounsfield units [HU]) of the
      implantation site. All implant sockets were prepared using 2 different types of
      stereolithographic surgical guide. Ninety-four implants were installed using the
      surgical guides (Stentcad Beyond, Ay-Design; Kos-gep, ODTU, Ankara, Turkey) in
      the mouth, whereas 122 implants were placed after the surgical guides (Stentcad
      Classic; Kos-gep, ODTU) were removed. RESULTS: The mean bone densities of maxilla
      and mandible were 561.36 (SD, 229.46) HU and 890.63 (SD, 361.85) HU,
      respectively. The mean angular deviations between planned and placed implants
      using Stentcad Classic and Stentcad Beyond surgical guides were 5.32 (SD, 1.96)
      degrees and 3.73 (SD, 1.14) degrees, respectively. Highly negative correlation
      was found between the bone density of the placed implant sites and angular
      deviations in the group in whom implants were installed with freehand.
      CONCLUSIONS: The lower bone density values have resulted in the greater angular
      deviations in the group, in whom the implants were placed after the surgical
      guides were removed. This deviation might have been derived from the freehand
      placement of the implants and the poor quality of the bone.

PMID- 21959427
TI  - Single-stage frontalis muscle flap for full-thickness reconstruction of the upper
      eyelid.
AB  - BACKGROUND: Full-thickness upper eyelid defects present a reconstructive
      challenge. Defects greater than 50% of the upper eyelid have traditionally been
      reconstructed with bulky full-thickness forehead flaps, Cutler-Beard flaps,
      Mustarde eyelid switches, and cheek rotation advancements, all mandating a second
      stage surgical procedure. We propose a novel technique for full-thickness upper
      eyelid reconstruction based on a frontalis muscle flap elevated from the
      resection defect, thus resulting in no additional forehead scar. METHODS: Our
      patient is a 48-year-old woman with an enlarging right upper eyelid sebaceous
      cell carcinoma. A subsequent single-stage resection resulted in a medial full
      thickness defect of 75% of the upper eyelid. The lateral and medial canthi were
      preserved. A palatal mucoperiosteal graft was harvested for the reconstruction of
      the posterior lamella. Dissection was carried through the excision defect in a
      preseptal plane over the supraorbital rim and subcutaneously over the frontalis
      muscle. A caudally pedicled frontalis muscle flap was elevated and inset to the
      defect edges with mild tension. Reconstruction of the skin defect of the upper
      eyelid was completed with a full-thickness preauricular skin graft. RESULTS: The
      patient had no complications and demonstrated good function and aesthetic result
      at 15 weeks and at 9 months postoperatively. CONCLUSIONS: Frontalis muscle flap
      based reconstruction offers a viable option for upper eyelid defects that are
      full thickness and encompass more than 50% of the eyelid. We obtained a
      functionally and aesthetically pleasing outcome with this single-stage procedure
      using a preexisting incision with minimal donor-site morbidity.

PMID- 21959428
TI  - Primary liposarcoma in oral and maxillofacial region.
AB  - Liposarcoma as one of the most common soft-tissue sarcomas in adults rarely
      occurs in oral and maxillofacial region. Its rarity makes a systematic and in
      depth understanding of these uncommon entities extremely difficult. Here we aimed
      to characterize and analyze the epidemiology, clinicopathologic characteristics,
      treatment and prognosis of primary oral and maxillofacial liposarcomas by
      presenting our experience from a Chinese tertiary referral hospital and
      literature review. All relevant information was manually collected from medical
      records from the authors' department (1993-2009) and literature retrieval
      (Jan.1940-Sep.2009). A total number of 150 patients were identified and included
      with mean age 49.1 years old and a slight male preponderance. These lesions
      mostly occurred in tongue (32.0%) followed by buccal region (28.7%) and were
      diagnosed as atypical lipmatous tumor/well-differentiated (58.45%) and myxoid
      liposarcomas (27.5%) by pathologic re-evaluation and re-categorization based on
      2002 WHO classification scheme. Complete surgical excision with negative margins
      was the primary treatment modality, while therapeutic utilities of adjuvant
      radiotherapy/chemotherapy remained controversial. Our data reinforced
      histopathologic subtype as one of key prognostic factors irrespective of gender,
      age and primary sites for this malignancy. More importantly, our analysis further
      revealed that tumor size (especially when larger than 3.6 cm) served as another
      important prognostic factor suggesting higher rates of disease-related death.
      Taken together, these findings might for the first time provide comprehensive
      information regarding the epidemiology, clinicopathologic features, treatment and
      prognosis of oral and maxillofacial liposarcoma.

PMID- 21959429
TI  - Comparative analysis of tranexamic acid use in minimally invasive versus open
      craniosynostosis procedures.
AB  - BACKGROUND: Intraoperatively administered tranexamic acid (TXA) lessens blood
      loss during orthopedic and cardiovascular surgery. Its use for craniosynostosis
      surgery warrants investigation. Therefore, we analyzed our use of TXA during
      minimally invasive (MI) and open craniosynostosis procedures. METHODS: Fifty-six
      patients were retrospectively studied: 20 in the MI group, 10 receiving TXA; 36
      in the open group, 16 receiving TXA. Study variables were weight-adjusted
      estimated blood loss (EBL) and calculated blood loss (CBL), transfusion and
      incidence, transfusion volume, and complications. Calculated blood loss was
      determined by a novel formula based on red cell mass. RESULTS: In the MI group,
      median EBL was significantly lower for TXA recipients (9.62 vs 15.94 mL/kg, P =
      0.0231), whereas median CBL was not (36.59 vs 34.12 mL/kg, P = 0.7976).
      Transfusion incidences were 80% TXA versus 100% control (P = 0.4737). Median
      transfusion volume trended lower (10.76 vs 19.43 mL/kg, P = 0.0723).In the open
      group, median EBL and CBL for TXA recipients were lower but not significantly
      different than for nonrecipients (21.86 vs 23.40 mL/kg, P = 0.7416; 53.54 vs
      80.13; P = 0.3137). All patients had a transfusion. Median transfusion volume for
      TXA recipients versus nonrecipients was 34.01 versus 40.35 mL/kg (P = 0.3137).
      Tranexamic acid greatly minimized the range of EBL and CBL in both surgical
      groups. There was a significant correlation between the CBL and EBL (P < 0.0001).
      There were no adverse events. CONCLUSIONS: Intraoperative TXA administration is
      safe with modest benefit suggested, especially in the MI group. Calculated blood
      loss correlated well with EBL at lower blood loss volumes, implicating it as a
      potential measurement of true blood loss.

PMID- 21959430
TI  - Patholologic fracture of the mandible after removal of follicular cyst.
AB  - OBJECTIVE: The objective of the study was to report a 61-year-old man who
      presented a complication after mandibular follicular cyst removal. METHODS: The
      patient underwent surgery, via intraoral approach: removal of the lesion and the
      dental follicle with curettage and extraction of the mandibular right third
      molar. Two weeks after surgery, the patient reported a slight malocclusion. The x
      ray showed a fracture near the right mandibular angle. The fracture was treated
      by application of a long mandibular plate. RESULTS: Two years after surgery, the
      patient is asymptomatic. Inferior alveolar nerve sensitivity returned completely.
      CONCLUSIONS: In the reported case, a satisfactory result was obtained after the
      treatment of the complication confirmed by postoperative x-rays.

PMID- 21959431
TI  - Croissant-shaped v-y advancement flap with 2 horns for repair of small- and
      medium-sized facial defects.
AB  - BACKGROUND: The use of a V-Y advancement flap is an effective technique for the
      reconstruction of small facial defects. However, in some areas, the use of a
      conventional V-Y advancement flap is not possible because of the tension caused
      by size variation. In the current study, we modified this method using a
      croissant-shaped V-Y advancement flap and repaired intermediate-sized defects
      without difficulty. MATERIALS AND METHODS: A croissant-shaped modified V-Y flap
      was used in 15 patients (aged 53-82 y). To completely remove masses, wide
      excisions were performed in all cases (nasolabial area = 7, nasojugal area = 3,
      medial canthal area = 1, cheek = 2, nose = 1, forehead = 1), and the average size
      of the defects was 2.6 * 2.5 cm. The flap was designed after confirmation of
      clear resection margins on frozen section. The long axis of the V-flap was 1.5 to
      2 times the length of the diameter of the defect and parallel to the nasolabial
      or nasojugal fold. In a conventional V-Y advancement flap, the lateral limbs of
      the V-flap begin at the end point of the central limb. However, in our design,
      the incision lines of the lateral limbs of the V-flap were extended to the end
      point of the defect to form a more convex shape. The flap was elevated in the
      subcutaneous layer above the mimetic muscles. The bilateral tips of the horns of
      the V-flap were sutured to each other and fixed medially to cover the distal
      aspect of the defect. The flap was then sutured with a 6-0 nylon. Donor site
      closure was performed with 6-0 Vicryl and 6-0 nylon in 2 layers. A Penrose drain
      was inserted at the donor site. RESULTS: No complications were reported in any of
      the 15 cases. In 2 cases, there was minimal flap congestion immediately after
      surgery. However, in both cases, the congestion spontaneously resolved during the
      ensuing days. At follow-up (mean, 12 mo), all 15 patients demonstrated
      satisfactory cosmetic results. CONCLUSIONS: This modified croissant-shaped V-Y
      flap may serve as an alternative to conventional V-Y flaps for reconstruction of
      soft tissue defects on the face.

PMID- 21959432
TI  - Correction of earlobe cleft with tongue-in-groove technique.
AB  - Cleft earlobe is a common surgical problem, which can be easily managed in an
      outpatient setting. There are various surgical techniques to repair this
      condition. Our method, the "tongue-in-groove technique" for the cleft earlobe
      repair, composed of 3 right-angled Z-plasties on the anterior, inferior, and
      posterior surfaces of the earlobe, is described.Between January 2007 and January
      2010, a total of 13 patients presenting earlobe cleft underwent surgical
      correction using this tongue-in-groove technique. All patients were women and had
      a traumatic complete cleft earlobe. The lesions were unilateral in all cases: 8
      women had left-side lesion, and 5 women had a right-side lesion.The patients have
      been followed up for a period ranging from 6 months to 3 years after the
      operation. All patients healed uneventfully, without any complications. The
      resulting scar was minimal and aesthetically acceptable.Cleft earlobe is the most
      common complication of the ear that requires surgical correction. We introduce
      our method, the tongue-in-groove technique, which is aesthetically acceptable,
      preserves more volume of the earlobe, and is easy to perform.

PMID- 21959433
TI  - Influence of the maxillary sinus exposure in reduction malarplasty with an L
      shaped osteotomy.
AB  - BACKGROUND: The zygomatic bone forms the prominence of the midface and plays an
      important role in determining the human facial attractiveness. The Oriental face
      is mesocephalic, with a prominent zygomatic body and wide zygomatic arch.
      Nevertheless, as an oval face is considered ideal, reduction malarplasty is
      always requested by Oriental people. Currently, L-shaped zygomatic osteotomy is
      often reported in literature yet no previous study has documented the exact
      outcome of this approach after exposure of the maxillary sinus. The objective of
      the study was to investigate the outcome and complications of intraoral L-shaped
      zygomatic osteotomy with the opening of maxillary sinus. METHOD: All patients
      were subjected to computed tomography before and 12 months after surgery. All
      parameters were obtained with morphometric analysis for clinical evaluation, so
      as to reveal the change in maxillary sinus, postsurgical results, and
      complications. RESULTS: All patients were satisfied with the optimal outcome of
      reduction malarplasty. Morphometric analysis indicated that the volume and
      surface area of maxillary sinus statistically significantly changed before and
      after surgery. Complications included deeper nasolabial fold, infraorbital nerve
      injury, and so on, yet no patients reported infection or dental pulp necrosis.
      CONCLUSIONS: Intraoral L-shaped osteotomy of the zygoma can improve the
      appearance of the patients greatly, and the exposure of maxillary sinus caused
      only a few complications.

PMID- 21959434
TI  - Three-dimensional surgical guide for frontal-nasal-ethmoid-vomer disjunction in
      Le Fort III osteotomy.
AB  - The aim of this article was to describe the achievement and the clinical use of a
      new three-dimensional surgical guide for frontal-nasal-ethmoid-vomer osteotomy.
      The three-dimensional guide is based on a three-dimensional rapid prototyping
      model and provides the three-dimensional spatial orientation and depth for the
      frontonasal osteotome. The method was applied to a 7-year-old patient with Apert
      syndrome. This technique allowed a critical osteotomy path in Le Fort III surgery
      to be transferred in a secure, fast, and cost-effective way from the three
      dimensional rapid prototyping model to the operating room.

PMID- 21959435
TI  - A new alternative for reconstruction of the inferior medial canthal and nasal
      sidewall defects.
AB  - BACKGROUND: Reconstruction of the inferior medial canthal and nasal sidewall
      defects presents some particular problems resulting from the unique anatomy of
      this region such as the multiple contours and sigmoidal relaxed skin tension
      lines, differences in skin color and texture, and the anatomic limitations
      presented by the adjacent structures including lower eyelids, eyebrows, and
      lacrimal drainage system. PURPOSE: In this study, the authors represent a new
      local flap as a new alternative for reconstruction of the defects of the inferior
      medial canthal region and nasal sidewalls. METHODS: In this technique, defect
      closure is achieved by using 2 cutaneous flaps designed in an unequal z-plasty
      manner. The first flap is used to cover the defect, whereas the second flap is
      used for closure of the first flap's donor site. From October 2006 to May 2010, a
      total of 16 patients 38 to 80 years old underwent medial canthal and nasal
      sidewall reconstruction by using this procedure. The defect size ranged from 2.0
      to 3.2 cm in width. RESULTS: A tension-free defect closure was achieved in all
      patients. Except 1 patient who had slight pseudoepicanthus, there was no patient
      with distortion of the surrounding anatomic structures. During a mean follow-up
      period of 30 months (5 months to 31/2 years), all patients were satisfied with
      the cosmetic and functional results. Except 1 patient who underwent reoperation
      for tumor recurrence, no patient required further surgery. CONCLUSIONS: The
      reading man procedure was found to be a successful technique for the closure of
      inferior medial canthal and nasal sidewall defects. It allows tension-free
      closure of considerably larger defects without any additional healthy tissue
      excision and and/or dog ear formation. Moreover, using z-plasty principle, it
      avoids distortions of the surrounding mobile anatomic structures.

PMID- 21959436
TI  - Ear elevation using 2-tiered costal cartilage on the same side as the
      reconstructed framework.
AB  - BACKGROUND: Ear elevation for the constructed auricle in patients with microtia
      is more difficult than total reconstruction of the auricle, although this
      procedure tends to be underestimated. Using costal cartilage for ear elevation
      may sometimes be difficult owing to its insufficient availability when it is
      harvested from the ipsilateral costal cartilage for the ear framework. We made
      both the ear framework and the base for elevation using only the unilateral
      sixth, seventh, and eighth costal cartilages to solve this problem. Our method
      for ear elevation is reported. SUBJECTS AND METHODS: The ear elevation procedure
      was performed in 28 patients with unilateral microtia. A 2-stage method was used,
      with framework assembling of the auricle in the first stage and ear elevation of
      the constructed auricle in the second stage. The technique was designed to make
      the entire constructed framework and base cartilage for elevation using only the
      unilateral sixth, seventh, and eighth costal cartilages RESULTS: All patients
      displayed an acceptable ear contour after the ear reconstruction procedure. There
      was no cartilage absorption or infection for 6 to 10 years after surgery. The
      auricular projections were well maintained, and the cephaloauricular angles of
      the constructed auricles were similar to the healthy ears at 6 to 10 years after
      surgery. Mean elevation was 32 degrees. CONCLUSIONS: The constructed auricle,
      which was made from only the costal cartilage ipsilateral to the framework, could
      be elevated to a mean angle of 32 degrees, and it could be maintained for 6 to 10
      years. This method is an option for elevating the constructed auricle.

PMID- 21959437
TI  - Endoscopic treatment of transnasal intracranial penetrating foreign body.
AB  - Transnasal intracranial penetrating injury is rare. We report a case of
      transnasal intracranial penetrating metallic chopstick, which was removed
      successfully by endoscopic approach, and management of transnasal intracranial
      penetrating injuries.

PMID- 21959438
TI  - Neuronavigation-guided endoscopic endonasal excision of an intraorbital
      intraconal cavernous hemangioma.
AB  - A 50-year-old man presented with the complaints of gradual decrease of visual
      acuity in his left eye since 2 years. Brain magnetic resonance imaging revealed a
      left intraorbital intraconal round mass lesion consistent with cavernous
      hemangioma. Binostril endoscopic endonasal approach was performed with the aid of
      neuronavigation. The lesion was well capsulated and easily dissected and resected
      totally without complication. Early postoperative course was uneventful. Three
      month follow-up after surgery revealed that the visual acuity and visual fields
      of the patient were normalized, and magnetic resonance imaging demonstrated total
      excision of the lesion.

PMID- 21959439
TI  - Registration strategy using occlusal splint based on augmented reality for
      mandibular angle oblique split osteotomy.
AB  - BACKGROUND: An augmented reality tool allows for visual tracking of real anatomic
      structures in superposition with volume-rendered computed tomographic or magnetic
      resonance imaging scans and thus can be used for navigated translocation of
      important structures during operation. In this feasibility study, ARToolKit was
      used in mandibular angle oblique split osteotomy to define the cutting planes
      according to an operative plan. METHODS: We overlay the operative plan on the
      model of a mandible made by rapid prototyping technology, and the technology was
      successfully used in 15 patients. Before the operation, all patients underwent
      computed tomographic scan, and dental casts were prepared by surgeons. Then,
      surgeons make the occlusal splint according to a dental cast to fix the marker,
      which can be recognized by the ARToolKit. The occlusal splint and marker were
      transformed to three-dimensional data using a laser scanner, and a programmer
      that runs on a personal computer named Rapidform matches the marker and the
      mandible image to generate the virtual image. By this step, the virtual image
      describing the marker, occlusal splint, and the mandible image of the patient are
      integrated. During the operation, the operative plan was overlaid on the rapid
      prototyping model of the mandible as soon as the ARToolKit recognized the marker.
      RESULTS: The technology was successfully used in 15 patients; the virtual image
      of the mandible and the cutting-plane both overlaid the real model of the
      mandible. CONCLUSIONS: This study has reported a new and effective way for
      mandibular angle oblique split osteotomy, and using occlusal splint might be a
      powerful option for the registration of augmented reality. Augmented reality
      tools like ARToolKit may be helpful for control of maxillary translocation in
      orthognathic surgery.

PMID- 21959440
TI  - Application of CAD/CAM prefabricated age-matched templates in cranio-orbital
      remodeling in craniosynostosis.
AB  - Infants with craniosynostosis involving the metopic and coronal sutures require
      cranio-orbital reshaping to correct craniofacial dysmorphologic feature and to
      improve facial balance. Currently, surgical techniques to create a balanced
      fronto-orbital region are based on the surgeon's subjective approach and artistic
      vision in creating a normal shape to the forehead. To date, the use of age
      matched templates and computer-assisted design/computer-assisted manufacturing
      techniques in optimizing the outcomes of surgical intervention in this area have
      not been explored. The aim of this article was to describe the process of
      template generation and application based on age-matched controls using computer
      assisted design/computer-assisted manufacturing technology and to present this
      application in 2 cases.

PMID- 21959441
TI  - Use of three-dimensional MRI-angiography in preoperative evaluation and
      postoperative management of hemangiomas of head and neck region.
AB  - Hemangiomas (proliferating endothelial tumors) are the most common benign tumors
      of infancy. Most often hemangiomas are self-regressing lesions without any
      treatment. Approximately 10% of hemangiomas cause complications such as major
      ulceration/destruction, distortion of involved tissues, and obstruction of a
      vital structure. When the situation becomes complicated, there are different
      treatment alternatives, ranging from systemic or local corticosteroid use to
      surgery. Sclerotherapy using intralesional polidocanol (Aethoxysklerol) injection
      may be used before surgery to decrease blood loss or when a vital structure of
      the face is in danger because of sudden increase in size of a surrounding
      hemangioma. Before any kind of treatment for both hemangiomas and vascular
      malformations, preoperative diagnosis and anatomic position of the lesion must be
      documented thoroughly. With the help of magnetic resonance imaging,
      tridimensional vascular pattern of such lesions can be shown successfully. We
      used three-dimensional contrast-enhanced time-resolved magnetic resonance
      angiography to detect the changes of lesions for 2 children who have large
      hemangiomas on their faces, before and after sclerotherapy with polidocanol
      injection. The findings of three-dimensional magnetic resonance imaging studies
      help to better assess the success rate of treatment not only for us as the
      physicians but also for the parents of these children who cannot understand
      anything with standard two-dimensional radiologic imaging.

PMID- 21959442
TI  - Anterior superior alveolar artery and horizontal maxillary osteotomy.
AB  - The aim of this study was to elucidate the location of the anterior superior
      alveolar artery relating to horizontal maxillary osteotomy.Fourteen hemifaces of
      7 Korean adult cadavers were studied. Three horizontal cuts were made at the
      level of the anterior nasal spine (ANS), halfway between ANS and distal end of
      nasal bone (DNB), and a lower quarter from ANS to DNB. The location of the
      canalis sinuosis (CS) was measured on a rectangular coordinate. The x axis was a
      horizontal (cross) line on the lower border of the piriform aperture. The z axis
      was at the lateral border of the piriform aperture vertical to the x axis, and
      the y axis was perpendicular (anterior and posterior) line at 0 point of x and z
      axes. Blocks including 3 levels were decalcified, cut in 10-MUm thickness, and
      stained with hematoxylin and eosin. Specimens were observed under a light
      microscope.Canalis sinuosis was found in all 14 hemifaces and ran in a
      curvilinear course along the piriform aperture. At the ANS level on the z axis,
      CS was located at 0.8 (1.8) mm medial to the y axis and 2.0 (0.9) mm posterior to
      the x axis. At a lower quarter from ANS to DNB, CS was located 1.6 (0.9) mm
      lateral to the y axis and 1.60 (0.8) mm posterior to the x axis. At halfway from
      ANS to DNB, CS was located 2.6 (1.3) mm lateral to the y axis and 1.70 (0.5) mm
      posterior to the x axis. In all histology specimens, vessels and nerves were
      found in small bony canal near the anterior wall of the maxilla. Arteries are
      well identified by their thick smooth muscle layer.In performing the horizontal
      maxillary osteotomy, surgeons should be aware of the presence of CS, which
      contains the anterior superior alveolar artery within 2 to 3 mm along the
      piriform aperture.

PMID- 21959443
TI  - Thickness of orbicularis oris muscle in unilateral cleft lip: before and after
      labial adhesion.
AB  - BACKGROUND: Our protocol for closure of unilateral complete or severe incomplete
      cleft lip begins with active dentofacial orthopedics (Latham device) followed by
      nasolabial adhesion and alveolar gingivoperioplasty. We have observed that
      preliminary adhesion provides more orbicularis oris muscle for the second-stage
      labial repair. METHODS: A quantitative prospective assessment of all patients
      undergoing nasolabial adhesion by the senior author between November of 2009 and
      July of 2010 was undertaken to assess whether there is an increase in lateral
      orbicularis oris muscle mass by the time of formal repair. Standard
      anthropometric points were placed before nasolabial adhesion and again at the
      second-stage closure. Ultrasonographic measurements of orbicularis muscle
      thickness were made on both lateral labial elements along a line drawn between
      sbal and cphi. The mean interval increase in thickness of lateral orbicularis
      oris was determined. RESULTS: Sixteen patients underwent nasolabial adhesion
      during the study period. Four patients with asymmetric bilateral cleft lip
      patients and 2 patients who did not have a second ultrasonographic study were
      excluded. The remaining 10 patients in the study had a nasolabial adhesion at a
      mean age of 3.9 months (range, 3.1-4.3 months). Mean orbicularis oris thickness
      before adhesion was 0.7 mm on the cleft side and 1.2 mm on the noncleft side. The
      increase in orbicularis thickness after the mean interoperative interval of 2.9
      months (range, 2.6-3.5 months) was calculated. On the cleft side, there was 0.8
      mm (138%) mean increase in orbicularis oris muscle thickness compared with 0.4 mm
      (32%) mean increase on the noncleft side. CONCLUSIONS: Labial adhesion in
      preparation for repair of unilateral complete or severe incomplete cleft lip
      results in a measurable increased thickness of lateral orbicularis oris. This
      additional muscular bulk is useful in construction of the philtral ridge.

PMID- 21959444
TI  - Muscle fiber types of human orbicularis oculi muscle.
AB  - The aim of this study was to elucidate the muscle type of the preseptal,
      pretarsal, and ciliary parts of the orbicularis oculi muscle in humans using
      immunostaining. The eyelids of 5 Korean adult cadavers were used (3 male and 2
      female cadavers; age range, 50-85 years). A 1:1000 mouse monoclonal anti-skeletal
      myosin antibody solution (fast, M4276; Sigma, St Louis, MO) was used for
      immunostaining. On sagittal sections, preseptal, upper pretarsal, midpretarsal,
      lower pretarsal, and ciliary (muscle of Riolan) parts were selected, and 0.38 *
      0.038-mm rectangular areas (0.1444 mm) were photographed. The number and size of
      the muscle fibers in each part of the orbicularis oculi muscle were evaluated by
      the image analyzer program and calculated per unit area (1 mm).On the whole, fast
      fibers (mean, 87.8% +/- 3.7%; range, 85.6%-91.7%) occupied a significantly larger
      portion of the muscle (P = 0.000 [t-test]) than nonfast fibers (mean, 12.2% +/-
      3.7%; range, 8.3%-14.4%). Among the 3 areas (preseptal, pretarsal, and ciliary
      parts), the ciliary part had a significantly (P = 0.019 [Scheffe]) higher portion
      (91.7%) of fast fibers than the pretarsal part (86.6%). The diameter of the fast
      fibers (mean, 17.7 +/- 2.6 MUm) was significantly greater (P = 0.000 [t-test])
      than the nonfast fibers (mean, 13.0 +/- 2.1 MUm).Our results showed that the
      eyelid has a higher proportion of fast muscle fibers than the mouth (pars
      peripheralis, 73% fast fibers; and pars marginalis, 66% fast fibers). Thus,
      closing of the eyelids is faster than closing of the mouth; however, the duration
      or power associated with closing of the mouth is stronger than closing of the
      eyelids.

PMID- 21959445
TI  - Anatomy and tensile strength of the zygomatic ligament.
AB  - The aim of this study was to elucidate the precise anatomic and histologic
      structure and tensile strength of the zygomatic ligament (ZL).Nine hemifaces of 7
      Korean adult cadavers were dissected, and 5 were prepared for histologic
      examination. The locations of the bony attachment areas of the ZLs were measured
      on rectangular and polar coordinates. The x axis was a horizontal line across the
      lower border of the superficial lateral canthal ligament. The y axis was a
      vertical line at the lateral border of the orbital rim. The tensile strengths of
      the ZLs were measured using a force gauge.Each ZL was attached from the zygoma to
      the dermis. The bony attachment area of the ZL was rectangular shaped. The
      thickness (mean +/- SD) at its origin was 0.8 +/- 0.2 mm, and the width was 8.1
      +/- 0.7 mm with a bone-to-dermis height of 6.5 +/- 0.6 mm. The axis was 19
      degrees inclined to the horizontal line. The vertical distance from the x axis to
      the lateral end and to the medial end of the ZL was 23.4 +/- 2.1 mm and 26.0 +/-
      1.3 mm, respectively. The horizontal distance from the y axis to the medial end
      and to the lateral end of the ZL was 8.3 +/- 2.7 mm and 14.9 +/- 3.2 mm,
      respectively. The distance from the origin to the medial end and to the lateral
      end of the ZL was 28.2 +/- 1.6 mm and 28.9 +/- 2.6 mm, respectively. The angle
      between the y axis and the medial and the lateral end of the ZL was 16.4 +/- 5.3
      degrees and 14.0 +/- 1.7 degrees, respectively. The parasagittal section of the
      cheek skin of the ZL contained an oblique bundle of fibers, which connected the
      dermis to the periosteum. The breaking strength of the ZL was 26.8 +/- 1.8 N
      (range, 22.5-32.9 N).Knowledge of the location, shape, and mechanical properties
      of the ZL is essential in face rejuvenation surgery.

PMID- 21959446
TI  - Pediatric nasoorbitoethmoid fractures.
AB  - The pediatric craniofacial trauma literature largely focuses on the management of
      mandible fractures, with very little information focusing on pediatric midface
      fractures, specifically nasoorbitethmoid (NOE) fractures. Because the diagnosis
      and surgical treatment plan for adult NOE fractures is well established in the
      literature, the treatment algorithms for NOE are essentially a transfer of adult
      practices to pediatric patients. This article reviews the differences between the
      pediatric and adult facial skeleton and the pathology and presentation of NOE
      fractures in the pediatric craniomaxillofacial skeleton. It also presents the
      effects of NOE fractures on the growth and development of the pediatric facial
      skeleton and describes the current surgical management for NOE fractures.

PMID- 21959447
TI  - Effects of doxycycline, minocycline, and tetracycline on cell proliferation,
      differentiation, and protein expression in osteoprecursor cells.
AB  - Tetracyclines, including tetracycline (TC), minocycline (MINO), and doxycycline
      (DOXY), were widely used as topical therapy in treating periodontitis, which is
      an infectious disease of the gingival crevice caused by periodontopathic
      bacteria. In addition, TC is used during bone grafting procedures because of its
      anticollagenase activity, antibacterial effect, and fibroblast-stimulatory
      properties.In this study, the effects of TC on osteoprecursor cells were
      evaluated. The cytotoxic effect was determined by testing cell viability.
      Differentiation and mineralization were evaluated using an alkaline phosphatase
      activity test and alizarin red S staining. In addition, protein expressions
      related to bone formation, such as bone morphogenetic protein 2 (BMP-2), estrogen
      receptor alpha (ER-alpha), and estrogen receptor beta (ER-beta), were evaluated
      by using Western blot analysis.The morphology of the cells seemed normal, and
      their viability was not significantly affected when they were treated with 10 MUM
      MINO and 10 MUM DOXY. Cells treated with 10 MUM DOXY showed alkaline phosphatase
      activity that was comparable to the control. Results from the Western blot
      analysis showed that TC, MINO, and DOXY reduced the expression of BMP-2 and ER
      beta. Normalization of the protein expressions showed that 10 MUM DOXY retained
      87% in BMP-2 and 85% in ER-beta.Higher levels of these agents led to a dose
      dependent decrease of cellular differentiation and protein expression. There are
      several commercially available agents for TC, which has to be considered when
      applying the TC in local delivery applications.

PMID- 21959448
TI  - Reconstruction of cranial bone defects using Struthio camelus eggshell.
AB  - BACKGROUND: There are many synthetic materials for the treatment of bone defects,
      which have their own advantages and disadvantages. We aimed to compare the
      efficacy of ostrich eggshell, which is cheap and easily available, and
      demineralized bone matrix in healing of cranial bone defects. METHODS: A full
      thickness circular bone defect was created in the frontal bone of 40 Wistar rats.
      Group 1 was the operative control group. In group 2, demineralized bone matrix
      applied into the defects; in group 3, Struthio camelus (ostrich) eggshell
      implants (OSIs) were applied into the defects; and in group 4, ostrich eggshell
      powders were applied into the defects. Computed tomographic analysis was
      performed to evaluate the healing of bone defects, the bone density, the OSI area
      measurements, and the OSI volume and density. At the end of the 24th week, all
      rats were killed. New bone formation, infection, resorption, and tissue reactions
      were evaluated. RESULTS: Ostrich eggshell implants were slightly resorbed,
      integrated with bone, stable, and supplied good cranial completeness. Ostrich
      eggshell powders were totally resorbed at the sixth month. There were no
      significant differences between control and ostrich eggshell groups in new bone
      formation. CONCLUSIONS: Ostrich eggshell did not seem to be an osteoproductive
      material, but it has some important advantages as an implant. Ostrich eggshell
      has a strong structure, is cheap, is shaped easily, and does not cause tissue
      reaction or infection. Ostrich eggshell could be a good alternative graft
      material for craniomaxillofacial procedures. Further studies are required to find
      out the potential use of the ostrich eggshell in craniomaxillofacial
      reconstructions.

PMID- 21959449
TI  - Isolation of epithelial cells in the developing primary lip and palate.
AB  - Failure of the primary lip and palate to fuse leads to clefts of the lip, a birth
      defect with an incidence of 1 for every 500 in some races. Epithelial cells
      lining the facial processes of the primary lip and palate, the lateral and medial
      nasal processes (LNP and MNP), must first make contact to go through a series of
      highly regulated and coordinated sequence of events to form the normal midface.
      As yet, many of the basic mechanisms underlying the fusion events of the
      epithelial-lined surfaces are not known. This is due in part to the difficulty
      associated with the isolation of the epithelial cells for further study and
      analysis. The objective of this study was to test the use of laser capture
      microdissection to collect clean populations of primary lip and palate epithelial
      cells destined to fuse. Fusing and nonfusing epithelial cell populations of the
      MNP and LNP were isolated by laser capture microdissection and assayed for gene
      expression of Bmp-4, Tgfbeta-2, and their type 1 receptors, Alk-3 and Alk-5,
      respectively. Transcripts of Bmp-4/Alk-3 and Tgfbeta-2/Alk-5 were restricted to
      the epithelial seam of the fusion site, and the epithelium of the prefusion site,
      in patterns previously reported. Data indicated our ability to isolate clean
      populations of epithelial and mesenchymal cells around the primary palate fusion
      site, allowing precise analysis of tissue and site-specific gene expression at
      high resolution. This study provides the basis of further analysis of the
      potential molecular players of MNP and LNP fusion and nonfusion of epithelial
      cells.

PMID- 21959450
TI  - Evaluation of hybrid porous biomimetic nano-hydroxyapatite/polyamide 6 and bone
      marrow-derived stem cell construct in repair of calvarial critical size defect.
AB  - Nano-hydroxyapatite/polyamide 6 (n-HA/PA6) composite scaffolds were prepared by a
      combined method of phase separation and particle leaching processing technique.
      The porous matrices were seeded with allogenic bone marrow-derived stem cells
      (BMSCs) and implanted in the critical-size calvarial defect (8-mm diameter) in
      rats. The adhesion, proliferation, and differentiation of BMSCs were demonstrated
      by (3-{4,5-dimethylthiazol-2yl}-2,5-diphenyl-2H-tetrazoliumbromide) assay,
      immunohistochemical staining, and scanning electron microscopy in vitro. Cell
      survival was tracked via fluorescent labeling in vivo. The regeneration process
      was evaluated by several techniques at 4, 8, and 16 weeks after implantation.
      According to the results, the porous n-HA/PA6 scaffolds are biocompatible and
      have no negative effects on the BMSCs in vitro. Nano-hydroxyapatite/polyamide 6
      composite combined with BMSCs exhibited good biocompatibility and
      osteoconductivity and enhanced osteogenesis at the initial stage after
      implantation. The results demonstrated that porous n-HA/PA6 scaffold is a
      potential matrix for bone tissue engineering, and using BMSCs as seed cells on
      porous n-HA/PA6 might be an alternative procedure in repair of large defect due
      to enhanced osteogenesis and osteointegration.

PMID- 21959451
TI  - Biomimetic matrices self-initiating the induction of bone formation.
AB  - The new strategy of tissue engineering, and regenerative medicine at large, is to
      construct biomimetic matrices to mimic nature's hierarchical structural
      assemblages and mechanisms of simplicity and elegance that are conserved
      throughout genera and species. There is a direct spatial and temporal
      relationship of morphologic and molecular events that emphasize the biomimetism
      of the remodeling cycles of the osteonic corticocancellous bone versus the
      "geometric induction of bone formation," that is, the induction of bone by
      "smart" concavities assembled in biomimetic matrices of macroporous calcium
      phosphate-based constructs. The basic multicellular unit of the corticocancellous
      bone excavates a trench across the bone surface, leaving in its wake a hemiosteon
      rather than an osteon, that is, a trench with cross-sectional geometric cues of
      concavities after cyclic episodes of osteoclastogenesis, eventually leading to
      osteogenesis. The concavities per se are geometric regulators of growth-inducing
      angiogenesis and osteogenesis as in the remodeling processes of the
      corticocancellous bone. The concavities act as a powerful geometric attractant
      for myoblastic/myoendothelial and/or endothelial/pericytic stem cells, which
      differentiate into bone-forming cells. The lacunae, pits, and concavities cut by
      osteoclastogenesis within the biomimetic matrices are the driving morphogenetic
      cues that induce bone formation in a continuum of sequential phases of
      resorption/dissolution and formation. To induce the cascade of bone
      differentiation, the soluble osteogenic molecular signals of the transforming
      growth factor beta supergene family must be reconstituted with an insoluble
      signal or substratum that triggers the bone differentiation cascade. By carving a
      series of repetitive concavities into solid and/or macroporous biomimetic
      matrices of highly crystalline hydroxyapatite or biphasic hydroxyapatite/beta
      tricalcium phosphate, we were able to embed smart biologic functions within
      intelligent scaffolds for tissue engineering of bone. The concavities assembled
      in the bioceramic constructs biomimetize the remodeling cycle of the
      corticocancellous bone and are endowed with multifunctional pleiotropic self
      assembly capacities, initiating angiogenesis and bone formation by induction
      without the exogenous applications of the osteogenic-soluble molecular signals of
      the transforming growth factor beta supergene family. The incorporation of
      specific biologic activities into biomimetic matrices by manipulating the
      geometry of the substratum, defined as geometric induction of bone formation, is
      now helping to engineer therapeutic osteogenesis in clinical contexts.

PMID- 21959452
TI  - Evaluation of the effects of guided bone regeneration and periosteum on newly
      formed bone in a distraction gap.
AB  - We determined the causes of bone resorption within a distraction gap and
      determined whether it could be prevented via guided bone regeneration during
      distraction. Another goal was to determine the effect of periosteum in bone
      healing in a distraction gap.Twelve sheep mandibles were bilaterally distracted.
      One side of the 6 sheep mandibles formed the control group; the other side was
      the study group, from which the periosteum was excised and distraction was
      performed. In the other 6 sheep, on the study side, guided bone regeneration was
      applied with distraction; on the other study side, guided bone regeneration was
      applied, and the periosteum was excised at the distraction. At the end of a 1
      week latent period, all subjects were distracted 10 mm (1 mm/d), and we waited 3
      months for consolidation. At the end of this period, all animals were killed, and
      radiologic evaluations of the newly formed bone within the distraction gap were
      conducted.The surface area of the regenerating bone in the membrane groups was
      significantly higher than in the groups without a membrane. However, no
      additional effect of the periosteum on the bone surface area was observed. No
      significant difference between the groups in densitometric values was
      observed.Concomitant use of guided bone regeneration with distraction
      osteogenesis may be the optimal way to generate a flat bone surface within a
      distraction gap.

PMID- 21959454
TI  - Effects of fibroblast growth factor 2 on osteoblastic proliferation and
      differentiation by regulating bone morphogenetic protein receptor expression.
AB  - Fibroblast growth factors (FGFs) are known to play a critical role in bone growth
      and development, affecting both osteogenesis and chondrogenesis. Fibroblast
      growth factor 2 (FGF-2) is produced intracellularly by osteoblasts and secreted
      into the surrounding matrix in bone.The dose-dependent effects of FGF-2 were
      tested to examine the relationship between FGF-2 and osteoblast proliferation and
      differentiation. Tests used included a cell viability test, an alkaline
      phosphatase activity test, and a Western blot analysis.Cultures growing in the
      presence of FGF-2 showed an increased value for 3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide assay and a decreased value for alkaline phosphatase
      activity. Results of the Western blot analysis showed that the addition of FGF-2
      seems to decrease osteocalcin and bone morphogenetic protein receptor IA.These
      data show that FGF-2 in the tested dosage within MC3T3-E1 cells seems to affect
      proliferation and differentiation. Results of the Western blot analysis may add
      some possible mechanisms, and it may be suggested that treatment of FGF-2 may
      have an influence on the expression of bone morphogenetic protein receptors in
      osteoprecursor cells. Further elucidation of the mechanisms related to this
      mechanism within the in vivo model may be necessary to ascertain greater detail.

PMID- 21959453
TI  - Immunohistochemical comparison of indermil with traditional suture materials in
      dental surgery.
AB  - The aim of this experimental study was to evaluate the effects of indermil on the
      closure of oral mucosa wounds in comparison with conventional sutures by
      investigating interleukin 1beta (IL-1beta) and tumor necrosis factor alpha (TNF
      alpha) markers immunohistochemically in an animal model.The animals were
      anesthetized by intraperitoneal injection of ketamine (90 mg/kg body weight).
      Straight incisions were made to the buccal mucosa of the animals. Animals were
      randomly assigned to 5 groups. Five different materials were used in the study.
      These were silk, plain catgut, monocryl, vicryl rapide (polyglactin 910), and
      indermil (N-butyl-2-cyanoacrylate). The wounds were closed primarily. After the
      region of wounds was examined clinically at the 2nd, 7th, 14th, and 21st days,
      excisional biopsies were performed, and the tissue samples were examined
      histopathologically and immunohistochemically.On the 14th day, TNF-alpha and IL
      1beta levels were high in the plain catgut group, moderate in the indermil group,
      and mild in the monocryl, silk, and vicryl rapide groups. On the 21st day, TNF
      alpha and IL-1beta levels were moderate in the plain catgut group, mild in the
      indermil and monocryl groups, and nonsignificant in the silk group. After the
      second day, TNF-alpha and IL-1beta levels were mild in the monocryl, silk, and
      vicryl rapide groups.Plain catgut had more negative effects than indermil on
      wound healing. Indermil should be applied to oral mucosa wounds together with
      sutures to provide better tissue support.

PMID- 21959455
TI  - Early partial monolateral zygomatic arch defect leads to unilateral craniofacial
      malformation.
AB  - OBJECTIVE: This study used reconstructed three-dimensional imaging to examine the
      influence of early partial monolateral zygomatic arch defect on the craniofacial
      development in a minipig model. METHODS: Five 7-week-old Chinese minipigs were
      used in this study. Each of them underwent skull radiography, three-dimensional
      computed tomography (CT), and surgery at 8 weeks of age. Bilateral zygomatic
      arches were randomized and divided into the experimental side and the control
      side. A standard 2-cm-long zygomatic arch defect was made by an electric drill on
      the experimental side. The contralateral side was left intact. One of them
      underwent skull radiography and three-dimensional CT 2, 4, 8, and 12 weeks after
      surgery. The other 3 minipigs underwent scanning 4, 8, and 12 weeks after
      surgery. The bone defect was observed by radiography and three-dimensional CT.
      All three-dimensional CT data were examined by Mimics 10.01 software, and three
      dimensional images were reconstructed. The length of both zygomatic arches, the
      length and width of the skull, and the hemicranial angles of both sides were
      measured and compared. RESULTS: The zygomatic arch developed to a summit at
      approximately 20 weeks of age. The zygomatic arch length of the experimental side
      is longer than that of the control side at each time point after surgery. The
      hemicranial angle of the experimental side is less than that of the control side
      at each time point after surgery. CONCLUSIONS: Early partial monolateral
      zygomatic arch defect accelerates its growth in the sagittal plane and impedes
      the hemicranial growth in the coronal plane. Early reconstruction of zygomatic
      arch defect may be essential to minimize the developmental craniofacial
      malformation in children.

PMID- 21959456
TI  - Feasibility of demineralized bone matrix for craniomaxillofacial contour
      restoration.
AB  - Demineralized bone matrix (DBM) could be a good alternative for
      craniomaxillofacial contour restoration, especially in perialar, malar, temporal,
      and frontal regions. In this study, the histologic behavior of DBM was
      investigated in different tissue planes to determine its proper application plane
      for restoration of craniomaxillofacial contour deformities and defects.Forty
      Wistar rats were divided into 6 groups: (1) 0.3 mL of 0.9% saline was injected
      into the subperiosteal plane of the cranium, (2) 0.3 mL of DBM was implanted into
      the subperiosteal plane of the cranium, (3) 0.3 mL of 0.9% saline was injected
      into the subdermal plane on the left inguinal region, (4) 0.3 mL of DBM was
      implanted into the subdermal plane on the right inguinal region, (5) 0.3 mL of
      0.9% saline was injected between the left external and internal oblique muscles,
      and (6) 0.3 mL of DBM was implanted between the right external and internal
      oblique muscles. At the 8th week half of the rats and at 16th week the remaining
      rats were killed in each group, and tissue samples were harvested. Histological
      and immunohistochemical evaluation revealed new bone tissue and bone marrow
      formation in all planes that DBM was given.Demineralized bone matrix can provide
      satisfactory results in craniomaxillofacial contour deformities including
      forehead, temporal, and malar augmentations, as well as mental and perialar
      augmentations and saddle nose corrections, with supraperiosteal or deep
      subcutaneous applications. However, superficial applications must be avoided
      because of the possibility of palpation, because it induces hard bone tissue
      formation in all tissue planes.

PMID- 21959457
TI  - Correlation of images: technique for mandible biomechanics analysis.
AB  - Various experimental or physicomathematical methods can be used to calculate the
      biomechanical behavior of the mandible. In this study, we tested a new tool for
      the analysis of mandibular surface strain based on the correlation of images.
      Five fresh explanted human mandibles were placed in a loading device allowing
      replication of a physiologic biting exercise. Surfaces of the mandibles were
      prepared with white and black lacquer. Images were recorded by 2 cameras and
      analyzed with an algorithm to correlate those images. With the Limess Measurement
      & Software system and VIC 3D software, we obtained data output concerning
      deformations, strains, and principal strains. This allowed us to confirm strain
      distribution on the mandibular corpus and to focus on weak points. Image
      correlation is a new technique to study mandible biomechanics, which provides
      accurate measurements on a wide bone surface, with high-definition images and
      without modification of the structure.

PMID- 21959458
TI  - Recurrence of a simultaneous tumor of the parotid gland and scalp skin malignant
      fibrous histiocytoma.
AB  - Malignant fibrous histiocytoma (MFH) is one of the most common soft-tissue
      sarcomas and generally arises in elderly patients. Most often, MFH occurs in the
      extremities and the retroperitoneum; MFH of the head and neck region is only
      reported in 3% of all cases. The distant metastasis appears in one third of all
      cases, and those cases mainly involve the lung, regional lymph nodes, the liver,
      or bones. The main treatment of MFH of the head and neck is radical excision of
      the tumor with modified or radical neck dissection. Recurrences of MFH are
      commonly seen and identified within the first 2 years of treatment. We report a
      case of simultaneous MFH tumors of the parotid gland and of the scalp skin in an
      elderly male patient. The patient underwent a wide surgical excision of the
      lesion and referred to the oncology department for further treatment. However, 1
      month after chemoradiotherapy had commenced, there was a recurrence of the tumor
      over the skin on the right parotid region.

PMID- 21959459
TI  - Brucella melitensis infection within warthin tumor of the parotid gland.
AB  - Brucellosis is a zoonotic systemic infectious disease, and multiorgan involvement
      is commonly seen, but involvement of the neck is a rare presentation of
      brucellosis. Granulomatous infections of the parotid gland are extremely rare.
      Warthin tumor is a well-known benign neoplasm of the salivary glands. In this
      report, we describe a Warthin tumor associated with Brucella melitensis in the
      same parotid gland.

PMID- 21959460
TI  - Solitary myxoid neurofibroma of the soft palate.
AB  - The neurofibroma is a benign tumor of neural origin, not frequently located in
      the oral cavity, and, especially, extremely rare in the soft palate. When it
      occurs solitarily, it is a spontaneous tumor without any internal manifestations.
      We report a case of an isolated neurofibroma of the soft palate not associated
      with von Recklinghausen disease.

PMID- 21959461
TI  - A huge midline premaxillary cyst as a late complication of maxillary surgery.
AB  - A median palatal cyst is an uncommon nonodontogenic cyst, and patients usually
      present with a painless swelling or the sensation of a mass. The mass is
      typically a well-defined fixed swelling along the midline. The mass can cause
      slight elevation of the nasal floor or swelling and drainage from the hard
      palate. Surgical resection is usually recommended as a definite treatment.We
      treated a 30-year-old man with a premaxillary mass with nasal obstruction. He had
      undergone surgery on both the maxilla and the mandible to correct malocclusion 10
      years earlier. A physical examination revealed elevated mucosa of the nasal
      floor, resulting in near-total obstruction of the nasal cavity, and the gingival
      mucosa over the upper incisors was also swollen. Preoperative computed
      tomographic scan demonstrated a midline nonenhancing round cystic lesion in the
      premaxillary area. Surgical excision was performed via a sublabial approach under
      general anesthesia, and his recovery after surgery was uneventful.

PMID- 21959462
TI  - Bilateral respiratory epithelial adenomatoid hamartoma of the olfactory cleft
      penetrating into the endocranium.
AB  - Respiratory epithelial adenomatoid hamartomas (REAHs) of the nose and paranasal
      sinuses are relatively rare. These tumors usually do not extend over the
      boundaries of the nose and sinuses. The authors presented a 65-year-old man
      experiencing progressive hyposmia, followed by intermittent stubborn headache.
      The symptoms lasted for almost 2 years and were getting worse very slowly.
      Fiberendoscopy showed relatively discrete polypoid tissue occupying the olfactory
      cleft bilaterally. The computed tomography and magnetic resonance imaging
      suggested the possible lack of the cribriform plate and the unity and uniformity
      of the tissues located both in the endocranium and high in the nasal cavity. The
      clinical picture resembled very much a esthesineuroblastoma.The patient underwent
      endoscopic sinus surgery under the general hypotensive anesthesia. Frozen
      sections during the surgery showed REAH. The entire tumor was removed in a piece
      meal way, including both olfactory bulbs because they were involved within the
      pathologic tissue as well.This case showed that REAH could also be a locally
      aggressive process, penetrating even into the endocranium.

PMID- 21959463
TI  - Transient cardiac failure due to Takotsubo cardiomyopathy after surgical
      reduction of nasal fracture.
AB  - INTRODUCTION: Takotsubo syndrome, also known as ampulla cardiomyopathy, broken
      heart syndrome, idiopathic apical ballooning syndrome, and stress-induced
      myocardial stunning, has been first described by Japanese authors in 1996 and
      subsequently specified in 2001; it derives from the resemblance between the
      ancient round-bottomed, narrow-necked Japanese fishing pots used to trap octopus
      in Asia and the end-systolic appearance of the left ventricle on
      ventriculography. CLINICAL REPORT: We introduce the case of a woman who was
      involved in a traffic car crash and, subsequently, was admitted to the Maxillo
      Facial Unit of the Novara Major Hospital with a diagnosis of nasal fracture. She
      underwent general anesthesia for the reduction of the fracture; after surgery,
      she developed acute chest pain, elevated cardiac biomarkers, ischemic
      electrocardiogram changes, and transient akinesis of the left ventricle without
      significant epicardial coronary artery disease. A diagnosis of takotsubo syndrome
      was made. CONCLUSIONS: This syndrome, which presents the same clinical features
      of a ventricular failure, is probably underdiagnosed, but after the introduction
      of sophisticated cardiac imaging and coronary intervention, more cases are
      identified and an unnecessary thrombolytic therapy can be spared. This reversible
      condition, which is, to our knowledge, never mentioned after a
      craniomaxillofacial surgical procedure, should be considered in the diagnostic
      algorithm for all patients presenting with acute onset of chest pain, elevated
      cardiac biomarkers, and ischemic changes on the electrocardiogram after a general
      anesthesia.

PMID- 21959464
TI  - Maxillary cementoblastoma in a child.
AB  - Cementoblastoma is a rare benign tumor that almost always occurs in the premolar
      or molar region and more commonly in the mandible than in the maxilla. We present
      a unique incisor maxillary cementoblastoma in an 11-year-old child not previously
      described. To our knowledge, only 2 maxillary cases, both related to canine
      teeth, were described in the international literature. Thus, the aim of this
      article was to discuss the clinical presentation, diagnosis, and subsequent
      treatment of a patient with a cementoblastoma in the anterior maxillary region.

PMID- 21959465
TI  - Periodontal and prosthetic biologic considerations to restore biological width in
      posterior teeth.
AB  - The biologic width is an essential dental space that always needs to be
      maintained to ensure periodontal health in any dental prosthetic restorations. An
      iatrogenic partial fixed prosthesis constructed in lower posterior teeth
      predisposed the development of subgingival caries, which induced violation of the
      biologic width in involved teeth, resulting in an uncontrolled inflammatory
      process and periodontal tissue destruction. This clinical report describes a
      periodontal surgical technique to recover a violated biologic width in lower
      posterior teeth, by crown lengthening procedure associated with free gingival
      graft procedure, to ensure the possibility to place a modified partial fixed
      prosthesis in treated area. The procedure applied to recover the biologic width
      was crown lengthening with some modifications, associated with modified partial
      fixed prosthesis to achieve health in treated area. The modified techniques in
      both surgical and prosthetic procedures were applied to compensate the
      contraindications to recover biologic width by osteotomy in lower posterior
      teeth. The result, after 4 years under periodic control, seems to achieve the
      projected goal. Treating a dental diseased area is necessary to diagnose,
      eliminate, or control all etiologic factors involved in the process. When the
      traditional methods are not effective to recover destructed tissues, an
      alternative, compensatory, and adaptive procedure may be applied to restore the
      sequelae of the disease, applying a restorative method that respects the biology
      of involved tissues.

PMID- 21959466
TI  - Simpson-Golabi-Behmel syndrome associated with cleft palate.
AB  - We report a very rare case of anomaly in the maxillofacial region. This case is a
      patient with a cleft palate who had Simpson-Golabi-Behmel syndrome. This X-linked
      symptom was first described by Simpson et al in 1975 and is characterized by
      prenatal and postnatal overgrowth, as well as visceral and skeletal anomalies.
      The syndrome consists of a distinctive facial appearance with wide nasal bridge,
      anteverted nostrils, wide-open mouth, enlarged tongue, and large protruding
      maxilla and jaw. The cleft palate was repaired surgically using the push-back
      method.

PMID- 21959467
TI  - Retrobulbar lipofilling to correct the enophthalmos.
AB  - In this article, we describe an alternative procedure to restore the retrobulbar
      volume in enophthalmic patients. We report the case of a patient with a late
      enophthalmos we submitted to retrobulbar lipofilling to correct the defect. The
      preoperative assessment and the surgical technique are described in detail. The
      volume of fat injected was 3.2 mL, with a satisfying increase in exophthalmometry
      measurements. The procedure was well tolerated without complications. Retrobulbar
      lipofilling for enophthalmos appears to be a safe alternative technique for
      orbital volume enhancement. It avoids the use of alloplastic materials and allows
      to obtain good cosmetic results with an easy technique and minimal donor-site
      morbidity.

PMID- 21959468
TI  - Orthodontic-aided extraction of impacted third molar to improve the periodontal
      status of the neighboring tooth.
AB  - OBJECTIVES: In the present clinical report, we describe the management and the
      long-term (3-year) outcome of a periodontally compromised lower second molar
      healed by orthodontic-aided extraction of the neighboring impacted third molar.
      METHODS: A healthy 21-year-old woman referred signs and symptoms of pericoronitis
      of impacted tooth 48 and periodontal injury on the distal aspect of tooth 47. The
      wisdom tooth was surgically exposed, and an orthodontic appliance was anchored to
      the neighboring teeth to stimulate eruption. After 5 months, third molar could be
      easily extracted. RESULTS: Three years after extraction, clinical and
      radiographic controls revealed a complete healing of the periodontal defect.
      CONCLUSIONS: Orthodontic-aided extraction of impacted third molars may improve
      the periodontal status of the neighboring tooth. This protocol is not free from
      drawbacks and limitations and should be applied only when third-molar extraction
      is associated with a concrete risk of postoperative complications.

PMID- 21959469
TI  - Metastatic esthesioneuroblastoma secreting adrenocorticotropic hormone in
      pediatric patients.
AB  - The purpose of this article was to report a pediatric case of secondary cervical
      esthesioneuroblastoma involving the parapharyngeal lymph nodes. A 3-year-old boy
      came to our clinical observation because of a right lymphonodal mass evidenced by
      nuclear magnetic resonance and a diagnosis of Cushing syndrome associated with
      ectopic adrenocorticotropic hormone secretion, moon face, central obesity,
      asthenia, and hirsutism. At the age of 10 months, the patient underwent
      endoscopic surgery for asportation of the World Health Organization stage IV
      esthesioneuroblastoma. At 38 months of age, the patient underwent right
      parapharyngeal lymphadenectomy with surgical access by a double mandibulectomy.
      After surgery, serum ACTH, cortisolemia, and urinary excretion of cortisol were
      within the reference range. Blood pressure was recorded at 110/70 mm Hg. Moon
      face disappeared, as well as central obesity and hirsutism. Clinical report is
      presented together with brief review of literature.

PMID- 21959470
TI  - Clinical management of peripheral ameloblastoma.
AB  - Peripheral ameloblastoma is a rare epithelial odontogenic tumor, limited to the
      soft tissues of the gingiva or oral mucosa. Peripheral ameloblastoma represents
      approximately 2% to 10% of all ameloblastomas. It is always considered to be
      benign, but occasionally it may be locally aggressive or with malignant
      potential. In this article, we report 3 new cases of benign peripheral
      ameloblastoma and further discuss the clinical management of this disease.

PMID- 21959471
TI  - Ganglioneuroma of the base of the skull.
AB  - Ganglioneuromas are rare benign tumors originating from the ganglion cells of the
      sympathetic and parasympathetic nervous system. Ganglioneuromas in the base of
      skull are extremely rare. In this article, we describe a case of primary
      ganglioneuroma below the foramen ovale observed in a 38-year-old man. The lesion
      was asymptomatic. The patient underwent surgical intervention for diagnostic and
      therapeutic purposes. Craniomaxillofacial surgery was conducted by the oral and
      maxillofacial surgical team and the neurosurgical team. Combined frontotemporal
      preauricular infratemporal approach was used to expose the lesion. Cerebrospinal
      fluid leakage and facial paralysis did not occur postoperatively. The results of
      histopathologic examination indicated that the excised lesion was a
      ganglioneuroma. Clinical follow-up was done, and no recurrence has been observed
      up to now.

PMID- 21959472
TI  - Treatment of temporomandibular joint ganglion cyst.
AB  - Ganglion cysts of the temporomandibular joint are very rare and always
      misdiagnosed as synovial cyst, parotid gland tumor, or other cystic lesions. They
      present with pain, swelling, or dysfunction. Image studies could facilitate to
      identify the tumor mass from the adjacent soft tissue, but a definitive diagnosis
      could be made from the pathologic report.A 59-year-old woman presented to the
      clinics with a chief complaint of a painless swelling mass in the right
      preauricular region of 3-month duration. Computed tomography was performed, which
      showed a small radiolucent lesion adjacent to the right condyle. Local excision
      was performed, and the specimen was sent for histologic examination.Microscopic
      examination showed a cystic space walled by dense fibrous connective tissue
      without epithelial or endothelial lining. Immunohistochemical staining of these
      lining cells showed positivity for vimentin and negativity for cytokeratin. These
      findings were consistent with the diagnosis of ganglion cyst.Ganglion cysts
      present as unilobulate or multilobulate cysts that arise from the collagenous
      tissue and is filled with highly viscous fluid. It does not communicate with the
      joint cavity. In contrast, synovial cyst is a true cyst lined by cuboidal or
      flattened cells from the synoviocytes and is filled with gelatinous fluid. It may
      or may not communicate with the joint cavity. Excision is the treatment of choice
      of symptomatic cystic lesions. Incomplete excision of these lesions may cause
      further recurrence or infection. Thus, injection of hydrocortisone or aspiration
      may be considered as an alternative management.

PMID- 21959473
TI  - Adenoid cystic carcinoma associated with mucous retention cyst of the parotid
      gland.
AB  - Mucous retention cysts of the parotid gland are rare, and a coexistent adenoid
      cystic carcinoma is even an unusual occurrence. Such coexistent adenoid cystic
      carcinomas with mucous retention cyst of the parotid gland are difficult to
      diagnose clinically and, at times, stage difficulty in their management. We
      report a rare case of adenoid cystic carcinoma associated with mucous retention
      cyst of the parotid gland with its diagnostic and management dilemma in a 14-year
      old adolescent girl.

PMID- 21959474
TI  - Conservative treatment of odontogenic myxoma.
AB  - Odontogenic myxomas (OMs) are nonencapsulated rare benign tumors that can occur
      in gnathic bones. They are locally invasive and have a high recurrence rate.
      Radiologically, OMs show a multilocular (in the majority of cases) or unilocular
      radiolucency, with either distinct or poorly defined margins.
      Histopathologically, OMs are characterized by spindle-, wedge-, or stellate
      shaped cells loosely arranged in an abundant mucoid background. Myxomas are
      mainly asymptomatic. Radical surgery, excision, and enucleation followed by
      curettage of the surrounding bony tissue have all been advocated as treatment
      options. This study presents a successful case of conservative treatment of OMs
      with a 5-year follow-up.

PMID- 21959476
TI  - Alternative transoral approach for intranasal tooth extraction.
AB  - Intranasal ectopic eruption is an uncommon condition. Even if an intranasal tooth
      can be completely asymptomatic, sometimes a variety of nasal signs and symptoms
      may be associated, ranging from mild nasal congestion to recurrent epistaxis and
      purulent rhinorrhea. As a consequence, surgical removal is often required.
      Endoscopic extraction of the intranasal tooth has been reported to present
      several advantages with respect to traditional surgical approaches and thus
      recommended as routine treatment in such cases. However, when a tooth is impacted
      next to the nasal floor, an alternative approach could be needed. We suggest an
      alternative transoral approach to perform extraction of intranasal teeth, aimed
      at avoiding excessive bone removal to reach the nasal floor area and preventing
      the complications related to traditional intraoral buccal or palatal approach. It
      could represent a reliable alternative to traditional removal in the Oral Surgery
      Department.

PMID- 21959475
TI  - Long-standing postsurgical lower cranial nerve palsy mimicking a
      pharyngolaryngeal submucosal mass in an elderly patient.
AB  - Changes that occur as a natural part of senescence in the complex action of
      deglutition predispose to dysphagia and aspiration. This dysfunction is worsened
      in patients with preexisting anatomic or functional alteration such as in case of
      a postsurgical lower cranial nerve palsy. We present the case of a 72-year-old
      woman who underwent surgical resection of a right jugulotympanic tumor 33 years
      ago, resulting in lower cranial nerve palsy, and came to our attention referring
      a 4 months' history of progressive dysphagia in which a pharyngolaryngeal
      submucosal mass was suspected.

PMID- 21959477
TI  - Diagnosis and surgical treatment of a nasolabial cyst.
AB  - Nasolabial cysts are uncommonly diagnosed nonodontogenic soft tissue lesions
      located close to the nasal alar region of the face, presenting as extraosseous
      swelling in the region of the nasolabial fold. Nasolabial cysts are likely to
      remain undetected unless and until they become infected or are associated with
      facial deformity. Histologically, it is lined with nonkeratinized squamous
      epithelium or, more frequently, with respiratory-type cylindrical epithelium with
      goblet cells. The aim of this article was to present and discuss the surgical
      management of a case of nasolabial cyst and to briefly review the literature.

PMID- 21959478
TI  - Witch nose: an embarassing metaphor for nasal tip dermoid cysts.
AB  - Nasal dermoid cysts are one of the most frequent congenital pathologic lesions of
      the nasal area. These lesions may have intracranial extensions without any
      clinical evidence, which can be explained by the pathophysiologic development of
      the lesion, thought to be related to a delay or pause during the separation
      period of the dura and skin during embryogenesis. This factor is independent from
      the location and size of the lesion and may lead surgeons to misdiagnoses or
      inadequate treatments.In this article, 2 cases of nasal dermoid cysts localized
      at the tip of the nose are presented. Although these lesions can be seen anywhere
      from the root to the columella, nasal tip location is rare in previously
      published series. In the cases presented in this study, both patients are school
      aged and are faced with social and psychologic problems, as their friends call
      them "witch nose," in reference to the lesion at the tip of the nose. Vertical
      tip incision for complete excision of these lesions was performed after accurate
      radiologic imaging of the brain and possible intracranial extension. No
      complications or recurrence was seen in either patient.Although the treatment of
      dermoid cysts is surgical, operative planning should be made after complete
      physical and radiologic examinations. As the lesion may lead to psychologic and
      social problems because of its appearance, especially in children, therapy should
      not be delayed.

PMID- 21959479
TI  - Platelet-rich fibrin and piezoelectric surgery: a safe technique for the
      prevention of periodontal complications in third molar surgery.
AB  - PURPOSE: The surgical removal of impacted mesioangular mandibular third molars
      (3Ms) may produce trauma to the soft tissues and bony structures. In particular,
      healing of postextractive socket may cause periodontal defects at the distal root
      of the second molar. The aim of the present prospective study was to assess the
      outcomes of a surgical protocol to remove 3Ms including the use of ultrasound
      bone surgery devices and platelet-rich fibrin (PRF) as a grafting material.
      PATIENTS AND METHODS: Twenty-eight impacted mandibular 3Ms were removed. Fourteen
      3Ms were removed by piezoelectric osteotomy and PRF application. Instead, the 14
      3Ms of the control group were removed by piezoelectric osteotomy but without PRF
      application. Probing depth in the distal position for all the mandibular second
      molars was registered before and 6 months after surgery. RESULTS: No
      complications were encountered. In the study group, alveolar socket fulfillment
      was rated as sufficient in 4 cases and adequate in the remaining 10 cases,
      whereas in the control group, it was rated as insufficient in 3 cases, sufficient
      in 4 cases, and adequate in 7 cases. Mean preoperative periodontal probing in the
      control group was 3.78 mm, whereas in the study group, it was 3.93 mm.Six months
      after surgery, mean periodontal probing was 3.28 mm in the control group and 3.07
      mm in the study group. CONCLUSIONS: Combined action of PRF and piezoelectric
      surgery can be considered a safe and fine technique for third molar surgery and
      alveolar socket healing.

PMID- 21959480
TI  - Effect of rectal diclofenac and acetaminophen alone and in combination on
      postoperative pain after cleft palate repair in children.
AB  - Acetaminophen and diclofenac are prescribed as postoperative analgesic agents in
      children. However, the efficacy of their combination is not studied sufficiently.
      We compare the analgesic effects of acetaminophen, diclofenac, and their
      combination after cleft palate surgery. In this randomized clinical trial, 120
      children (1.5-5 y) who were scheduled for cleft palate repair were studied.
      Children were randomized to receive placebo, acetaminophen (40 mg/kg), diclofenac
      (1 mg/kg), or acetaminophen (40 mg/kg) plus diclofenac (1 mg/kg) rectally just
      after surgery. Acetaminophen (30 mg/kg) and diclofenac (1 mg/kg) were
      administered every 8 hours until 48 hours. Postoperative pain was assessed
      regularly with the Children Hospital of Eastern Ontario Pain Scale, and rescue
      analgesia was provided if scores were 7 or greater. Time to the first
      prescription of meperidine, total postoperative meperidine consumption, and
      adverse effects were the main outcomes.After surgery, pain scores were higher in
      placebo than in other groups in all time intervals. In the first 12 hours, pain
      scores in the combined group were less than those in the acetaminophen (P < 0.05)
      and diclofenac (P < 0.05) groups. Postoperative meperidine consumption was the
      highest in placebo and was the least in combined group (P < 0.05). It was
      significantly higher in the acetaminophen group than in the diclofenac group (P <
      0.05). Time to the first prescription of meperidine was significantly different
      among all groups. Adverse effects were comparable among groups.Rectal
      acetaminophen plus diclofenac was found to be the most effective in pain control.
      However, both rectal acetaminophen and diclofenac were more effective than
      placebo, whereas diclofenac was more effective than acetaminophen.

PMID- 21959481
TI  - Iatrogenic arteriovenous fistula of the superficial temporal artery after manual
      reduction of temporomandibular joint dislocation.
AB  - A 33-year-old man fell from a height and was referred to our hospital. Physical
      examination showed a swelling in the left preauricular region without laceration.
      No thrill or bruit was detected at this time. A face x-ray and a computed
      tomographic scan showed a left temporomandibular joint (TMJ) dislocation, Le Fort
      I fractures, and a mandibular body fracture. Left TMJ dislocation was treated by
      manual reduction. Two days after admission, a swelling in the left preauricular
      region progressed, with thrill and bruit. Left external carotid artery angiograms
      showed an arteriovenous fistula with a dilated pouch near the left TMJ. The
      fistula was fed by the left superficial temporal artery and drained into the left
      superficial temporal vein. The fistula was successfully embolized using Tornado
      coils. This is the first case of an arteriovenous fistula of the superficial
      temporal artery after manual reduction of TMJ dislocation.

PMID- 21959482
TI  - Unilateral facial paralysis caused by Ramsay Hunt syndrome.
AB  - The Ramsay Hunt syndrome is a rare disease caused by an infection of the
      geniculate ganglion by the varicella-zoster virus. The main clinical features of
      the syndrome are as follows: Bell palsy unilateral or bilateral, vesicular
      eruptions on the ears, ear pain, dizziness, preauricular swelling, tingling,
      tearing, loss of taste sensation, and nystagmus. We describe a 23-year-old white
      woman, who presented with facial paralysis on the left side of the face, pain,
      fever, ear pain, and swelling in the neck and auricular region on the left side.
      She received appropriate treatment with acyclovir, vitamin B complex, and CMP
      nucleus. After 30 days after presentation, the patient did not show any signs or
      symptoms of the syndrome. At follow-up at 1 year, she showed no relapse of the
      syndrome.

PMID- 21959483
TI  - Proptosis, congestion, and secondary glaucoma due to carotid-cavernous fistula
      after embolization.
AB  - Carotid-cavernous fistulas (CCFs) are traumatic or spontaneously occurring
      communications between the carotid artery and the cavernous sinus. Carotid
      cavernous fistulas can be due to a direct connection or indirect connections
      between the carotid artery system and the cavernous sinus. According to the
      etiologic classification, they may be of traumatic or spontaneous origin, and
      according to the angiography classification, they may be of direct or dural. Most
      CCFs are of spontaneous origin, and these are reported as frequently self-healing
      lesions. Spontaneous CCFs are mostly secondary to arteriosclerotic changes, which
      explains the increased ratio of elderly patients. Traumatic CCFs are usually of
      high-flow type and need intervention. The symptoms are various usually correlated
      to the size and type of venous drainage. The most frequent symptoms on
      presentation are proptosis, conjunctivitis, and chemosis; however, this picture
      may be complicated by optic nerve edema, cranial nerve palsies, and intracranial
      hemorrhage. We report a case with right low-flow dural CCF, which has worsened
      after angiography and recovered totally soon after endovascular embolization
      process.

PMID- 21959484
TI  - One-stage treatment of acquired facial deformity caused by severe unilateral
      condylar hyperplasia.
AB  - Condylar hyperplasia (CH) is a rare and self-limiting process manifesting between
      the first and third decades of life. It causes facial asymmetry and derangement
      of occlusion. The management involves resection of the condylar head and
      orthognathic surgery followed by orthodontic treatment. We present a 33-year-old
      man with spontaneous onset of CH during a span of 10 years. This was managed with
      resection of the condyle alone, which dramatically improved facial asymmetry in
      addition to restoration of the occlusion within a few months of follow-up.
      Therefore, orthognathic surgery or orthodontic treatment was not needed.

PMID- 21959485
TI  - Usefulness of vascularized galeal frontalis myofascial flap as treatment for
      postoperative infection in frontal sinus fracture.
AB  - Inappropriate treatments of frontal sinus fractures may lead to serious
      complications, such as mucopyocele, meningitis, and brain abscess. Assessment of
      nasofrontal duct injury is crucial, and nasofrontal duct injury necessitates
      sinus obliteration. For sinus obliteration, autogenous fat, muscle, bone,
      pericranium grafts, and alloplastic materials, such as Surgicel, hydroxyapatite
      (Bone Source), and methyl methacrylate, are commonly used. However, autogenous
      tissue grafts and alloplastic materials cannot prevent infection, which is the
      leading cause of complications of frontal sinus surgery. A good vascular supply
      is the mainstay of resistance against infection.A 21-year-old man had nasofrontal
      duct injury and frontal sinus fracture by motorcycle accident. He underwent
      cranialization and frontal sinus obliteration with autologous bone graft and
      hydroxyapatite. On 16 days postoperatively, the patient had a high temperature
      with wound infection in the glabella. Thus, he was treated with sinus
      obliteration with vascularized galeal frontalis myofascial flap. He was followed
      up postoperatively for 1 year without infection.The authors experienced a
      postoperative infection in frontal sinus fracture, which was treated with
      vascularized galeal frontalis myofascial flap and achieved satisfactory result;
      thus, we presented our case with reviews of the literature.

PMID- 21959486
TI  - What is the importance of radiology in obstructive sleep apnea?
AB  - Lipomas are rare, and they rarely arise in deep soft tissue. Only few cases
      associated with obstructive sleep apnea (OSA) have been reported. Because of
      radiologic examinations (computed tomography and magnetic resonance imaging) in a
      case with OSA, a rarely observed large lipoma was encountered in the
      retropharyngeal region. In the case that was followed, the apnea-hypopnea index
      was measured. The radiologic examination of the upper airway of the case with OSA
      symptoms was presented.

PMID- 21959487
TI  - Intradiploic epidermoid cyst of the temporal bone: is it the same as or different
      from cholesteatoma?
AB  - Intradiploic epidermoid cyst is a benign lesion that is derived from the
      ectodermal cells of the cranium. It is a rare tumor, representing less than 1% of
      all primary intracranial tumors. It can be located in any part of the skull, but
      frontal and parietal bones are the most common sites for the cysts. It occurs
      from the first to the seventh decade of life. Because it is a slowly growing
      tumor, it is usually discovered incidentally and may remain asymptomatic for many
      years. Rarely, it grows intracranially to produce brain compression or undergo
      malignant change. For treatment, it is important to completely remove the capsule
      of the cysts to avoid recurrence. I describe a 25-year-old man with an
      intradiploic epidermoid cyst of the temporal bone, who underwent tumor removal
      and simple mastoidectomy. I also describe the unique radiologic findings of my
      case, which differed from those of cholesteatoma.

PMID- 21959488
TI  - Intraoral sublabial approach for anterior skull base juvenile ossifying fibroma.
AB  - Juvenile ossifying fibroma is a rare fibro-osseous neoplasm seen in the pediatric
      age group of 5 to 15 years. It has been recognized as a separate histopathologic
      entity among the fibro-osseous group of lesions. Occasionally, it may grow
      aggressively and extend to involve the orbits and skull base, resulting in
      serious cosmetic and functional problems. We present a case of a juvenile
      ossifying fibroma arising below the skull base of a 9-year-old boy. This case
      demonstrates that cemento-ossifying fibroma in case of maxilla grow to
      considerable size before causing symptoms because of the remodeling of the
      surrounding bony compartment and intraoral sublabial approach can be used to
      excise lesion completely even at the skull base.

PMID- 21959489
TI  - White-eyed medial wall blowout fracture mimicking head injury due to persistent
      oculocardiac reflex.
AB  - White-eyed medial wall blowout fracture associated with muscle entrapment is
      rare. It may present with symptoms consistent with an intracranial injury,
      delaying the diagnosis and putting the patient at risk for permanent damage. A
      case of an isolated white-eyed medial wall fracture associated with persistent
      bradycardia on abduction secondary to oculocardiac reflex as well as limited
      abduction mimicking sixth-nerve weakness is presented. Patients with white-eyed
      medial wall blowout fracture with muscle entrapment can present with oculocardiac
      reflex symptoms, pain, diplopia, and strabismus in the absence of any signs on
      ocular examination except for abnormal motility. Computed tomography imaging of
      the orbit should be performed to confirm the diagnosis, followed by immediate
      surgical intervention to avoid ischemia and permanent injury.

PMID- 21959490
TI  - Review of "primary fibrinolysis is integral in the pathogenesis of the acute
      coagulopathy of trauma".

PMID- 21959491
TI  - Review of "natural history of supratentorial hemangioblastomas in von hippel
      lindau disease".

PMID- 21959492
TI  - An anatomist's contribution to blepharoptosis surgery: 100th anniversary of the
      Whitnall ligament.

PMID- 21959493
TI  - Bolster implementation of custom-made plaster in the reconstruction of cleft lip
      nose.

PMID- 21959494
TI  - Use of an endotracheal tube as a trochar in mandibular fracture fixation.

PMID- 21959495
TI  - Iatrogenic necrotizing fasciitis in a neonate.

PMID- 21959496
TI  - A combined experimental and computational study on the sulfoxidation by high
      valent iron bispidine complexes.
AB  - Iron-bispidine complexes are efficient catalysts for the oxidation of thioanisole
      to phenylmethylsulfoxide with iodosylbenzene as oxidant. With the tetradentate
      bispidine ligand L(1) (L(1) = 2,4-pyridyl-3,7-diazabicyclo[3.3.1]nonane)) the
      catalytic efficiency is smaller than with the pentadentate bispidine ligand L(2)
      (L(2) = 2,4-pyridyl-7-(pyridine-2-ylmethyl)-3,7-diazabicyclo[3.3.1]nonane)).
      Based on the redox potentials (iron complexes with L(1) are stronger oxidants
      than with L(2)) and known efficiencies in catalytic olefin oxidation and C-H
      activation reactions, the expectations were different. A DFT-based analysis is
      used to explain the apparent contradiction, and this is based on differences in
      the electronic ground states of the ferryl complexes as well as in the oxygen
      transfer transition states.

PMID- 21959501
TI  - The role of mitochondrial permeability transition in reperfusion-induced
      cardiomyocyte death depends on the duration of ischemia.
AB  - Mitochondrial permeability transition (MPT) is critical in cardiomyocyte death
      during reperfusion but it is not the only mechanism responsible for cell injury.
      The objectives of the study is to investigate the role of the duration of
      myocardial ischemia on mitochondrial integrity and cardiomyocyte death.
      Mitochondrial membrane potential (DeltaPsim, JC-1) and MPT (calcein) were studied
      in cardiomyocytes from wild-type and cyclophilin D (CyD) KO mice refractory to
      MPT, submitted to simulated ischemia and 10 min reperfusion. Reperfusion after 15
      min simulated ischemia induced a rapid recovery of DeltaPsim, extreme cell
      shortening (contracture) and mitochondrial calcein release, and CyD ablation did
      not affect these changes or cell death. However, when reperfusion was performed
      after 25 min simulated ischemia, CyD ablation improved DeltaPsim recovery and
      reduced calcein release and cell death (57.8 +/- 4.9% vs. 77.3 +/- 4.8%, P <
      0.01). In a Langendorff system, CyD ablation increased infarct size after 30 min
      of ischemia (61.3 +/- 6.4% vs. 45.3 +/- 4.0%, P = 0.02) but reduced it when
      ischemia was prolonged to 60 min (52.8 +/- 8.1% vs. 87.6 +/- 3.7%, P < 0.01). NMR
      spectroscopy in rat hearts showed a rapid recovery of phosphocreatine after 30
      min ischemia followed by a marked decay associated with contracture and LDH
      release, that were preventable with contractile blockade but not with
      cyclosporine A. In contrast, after 50 min ischemia, phosphocreatine recovery was
      impaired even with contractile blockade (65.2 +/- 4% at 2 min), and cyclosporine
      A reduced contracture, LDH release and infarct size (52.1 +/- 4.2% vs. 82.8 +/-
      3.6%, P < 0.01). In conclusion, the duration of ischemia critically determines
      the importance of MPT on reperfusion injury. Mechanisms other than MPT may play
      an important role in cell death after less severe ischemia.

PMID- 21959502
TI  - A quantitative EEG method for detecting post clamp changes during carotid
      endarterectomy.
AB  - OBJECTIVE: To apply univariate and multivariate analyses of EEG spectral features
      in order to detect subtle post-clamp changes during carotid endarterectomy, and
      to devise a data-driven, multivariate classification method for rapid, real-time
      detection of small post-clamp EEG changes. METHODS: We used intraoperative EEG
      records of 27 patients who underwent carotid endarterectomy (CEA) and did not
      undergo a shunt per surgeon's and technologist's visual inspection of the electro
      encephalogram (EEG). Furthermore, these records could not be flagged with r-sBSI
      (revised spatial brain symmetry index) or r-tBSI (revised temporal brain symmetry
      index) qEEG (quantitative EEG) metrics. Spectral energies of 10 s EEG snippets
      were recorded at 5 min intervals from 10 min pre-clamp to 20 min post-clamp.
      Using receiver operating characteristic curves, the power of standard EEG
      spectral bands in detection of post-clamp changes was determined. Next, we
      employed Fisher Linear Discriminant Analysis for classifier-guided multivariate
      feature selection and classification. RESULTS: In univariate analysis, delta
      waves in non-frontal areas, irrespective of the laterality of the affected
      hemisphere, were found to be generally more powerful indicators of clamp-induced
      EEG changes. In multivariate analysis, cross-validation results for Fisher LDA
      produced subject-independent equal error rates as low as 32% when separating post
      clamp signals from pre-clamp controls. Within our subject group, the intricate
      clamp-induced EEG signatures were predominantly anterior, bilateral, and had a
      strong delta rhythm presence. The overall post-clamp saliencies, both in
      univariate and multivariate analyses, were time-dependent. CONCLUSION: By
      applying automatic data-driven feature extraction and classification to short EEG
      records, it is possible to construct subject-independent computational models
      that can detect subtle post clamp changes possibly caused by small perturbations
      in cerebral blood flow. These subtle changes are missed by visual inspection of
      the EEG and by other quantitative EEG techniques such as r-sBSI and r-tBSI.
      Within our subject group, the intricate post-clamp EEG signatures were
      predominantly anterior, bilateral, and had a strong delta rhythm presence.

PMID- 21959503
TI  - Outcomes of renal transplantation in recipients with peak panel reactive antibody
      >30% under tacrolimus-based immunosuppression.
AB  - BACKGROUND: Renal transplant recipients with high panel reactive antibodies (PRA)
      have worse outcomes than those with lower PRA. High PRA re-transplant recipients
      are thought to have worse outcomes than high PRA first transplant recipients. In
      this study, we examined outcomes of renal transplantation recipients with a peak
      PRA >30% and compared the outcomes of first and re-transplanted recipients.
      MATERIAL/METHODS: Survival outcomes between recipients of first transplants
      (n=68) and re-transplants (n=155) operated between June 1990 and August 2000 were
      compared. Sub-group analysis was done based on patient's gender, race and
      first/re-transplant. All patients received tacrolimus-based immunosuppression.
      RESULTS: No difference in graft survival was noted between first and re
      transplanted patients. Ten-year patient survival was better in the re
      transplanted group (p<0.004). Factors affecting patient survival on univariate
      analysis were age >55 years (p=0.015), deceased donor transplant (p=0.009), first
      transplant patient (p=0.004) and diabetes mellitus (DM) as the cause of End Stage
      Renal Disease (ESRD) (p=0.005). On multivariable analysis, factors affecting
      patient survival were number of the transplant (re-transplant versus first
      transplant, Relative risk [RR]=0.54, p=0.009) and cause of ESRD (DM versus no DM,
      RR=1.91, p=0.012).Diabetes as a cause for ESRD was the only factor affecting
      graft survival on univariate(p=0.015) and multivariable analysis (DM versus no
      DM, RR=1.63, p=0.017). CONCLUSIONS: High PRA recipients of first transplants had
      poorer patient survival than high PRA re-transplants. On multivariable analysis,
      diabetes etiology of ESRD and first transplantation were found to be independent
      risk factors for poorer patient survival.

PMID- 21959504
TI  - Invasive fungal infections following liver transplantation - risk factors,
      incidence and outcome.
AB  - BACKGROUND: The incidence of invasive fungal infections (IFIs), particularly
      candidiasis and aspergillosis, following solid organ transplantation vary from
      1.4% to 42%. IFIs most commonly occur after orthotropic liver transplantation
      (OLT), lung/heart and pancreas transplantation. Mortality related to IFIs depends
      on the type of transplant and vary from 3% to 100% of cases. The results largely
      depend on early initiation of specific treatment for IFIs. Therefore, the
      diagnosis has to be prompt and based on known risk factors - time of surgical
      procedure, type of biliary anastomosis, blood loss, rate of rejection and re
      transplantation. MATERIAL/METHODS: We evaluated the incidence of fungal
      infections in patients after liver transplantation in our center. The
      retrospective analysis of 175 consecutive OLT patients was undertaken to estimate
      incidence, risk factors and clinical courses of IFIs in the last 6 years at our
      center. RESULTS: Infections involving Aspergillus (6 cases), Candida (24 cases)
      and Cryptococcus (1 case) were observed in 17.7% of our recipients. Except for 1
      case (Cryptococcus encephalitis), all of the episodes developed during the first
      month post-transplantation. All cases of lung aspergillosis developed in patients
      with autoimmune cholestasis prior to transplantation. In 1 case after
      transplantation, in a patient with bile duct necrosis requiring reoperation,
      pneumonia developed. In 3 cases, pulses of steroids were used to treat acute
      rejection. Apart from that, none of the potential risk factors of IFIs described
      by other authors were noted. Five out of 6 cases of aspergillosis survived on
      combined antifungal therapy. The recipient diagnosed with cryptococcal
      encephalitis died. All cases with urinary tract (n=18; 8.6%) or respiratory (n=6;
      3.4%) candidiasis survived. CONCLUSIONS: Early diagnosis and prompt treatment is
      fundamental for patient survival.

PMID- 21959505
TI  - Apoptosis of tubular epithelial cells in preimplantation biopsies of kidney
      grafts with immediate, slow and delayed function.
AB  - BACKGROUND: Apoptosis is a form of cell death observed in kidney grafts as a
      result of ischemia/reperfusion injury. The aim of our prospective study was to
      analyze the intensity of apoptosis in kidney tubules after cold storage in
      respect to early and 12-month post-transplant graft function. MATERIAL/METHODS:
      The intensity of renal tubular apoptosis was estimated by TUNEL method in
      proximal and distal tubules in 72 pre-implantation kidney biopsies. Sixteen
      patients with biopsies that did not fulfill Banff 97 classification, with early
      acute rejection or early graft loss, were excluded. Early graft function was
      defined as IGF (N=17) when serum creatinine (sCr) was <264 umol/l at 3(rd)
      postoperative day (POD); as SGF (N=20) when sCr >264 umol/l and not more than 1
      dialysis was performed; and as DGF (N=19) when more than 1 dialysis was done.
      RESULTS: The percentage of apoptotic cells was markedly higher in distal than in
      proximal tubules in all 3 groups. The percentage of apoptotic cells in distal
      tubules found was: 3.02% (1.03-5.00%) in IGF, 1.66% (0.92-2.39%) in SGF, and
      1.76% (0.84-2.68%) in DGF; these differences were not significant. In the IGF
      group the mean percentage of apoptotic cells in distal tubule was higher than in
      the other groups (not statistically significant). The subgroups of patients with
      higher and lower than median (1.35%) apoptotic cell range in distal tubules had
      similar graft function at the 12-month follow-up. CONCLUSIONS: The enhancement of
      tubular epithelial cells apoptosis in kidney grafts after cold storage does not
      determine its early and later excretory function.

PMID- 21959506
TI  - Ultrasonographic evaluation of disturbances in the perfusion of renal graft
      parenchyma as a result of acute occlusion of supernumerary arteries - a new
      application for contrast-enhanced ultrasonography.
AB  - BACKGROUND: The aim of this study was to assess the disturbances in perfusion of
      transplanted kidneys (KTx) following an acute occlusion of 1 of the supernumerary
      renal arteries (SRA). We compared the differences in echogenicity and the size of
      ischemic areas between routine B mode ultrasonography with Doppler evaluation (US
      CD) and contrast-enhanced ultrasound examination (CE-US). MATERIAL/METHODS: We
      present 4 KTx patients in whom we observed an occlusion of the SRA. After the
      initial diagnosis of occlusion of SRA in routine B mode with US-CD, the CE-US
      examination following intravenous contrast administration was performed. The
      disturbances of tissue perfusion in regions of interest, the level of signal
      intensity, and the size of the infarct were analyzed. RESULTS: The renal
      parenchyma in the routine B mode was characterized by low echogenicity. After the
      contrast medium administration, we observed increased echogenicity (-53.75+/-5.3
      dB vs. -28.75+/-3.8 dB, p<0.001). The echogenicity between the focus of the
      infarct and normal parenchyma in the routine B mode and US-CD was small, but the
      difference was larger for analogous areas in the CE-US (the mean signal
      intensity: -2.75+/-1.5 dB in the B mode/US-CD vs. -24.25+/-3.9 dB in CE-US,
      p<0.001). The size of the ischemic areas in the B mode and Doppler examinations
      were underestimated due to poor separation of the ischemic foci, and were much
      better visualized in the CE-US (-25.5+/-7.3 mm vs. -38.5+/-9.7 mm, p<0.001).
      CONCLUSIONS: CE-US may enable a precise evaluation of a graft's ischemic foci due
      to occlusion of SRA in the early post-transplant period.

PMID- 21959507
TI  - Progressive arterial stiffening in kidney transplant recipients.
AB  - BACKGROUND: Pulse wave velocity (PWV) is a marker of arterial stiffness. Data
      from general population and end-stage renal disease patients suggest that PWV
      increases with age by about 0.1 m/s for each year of life and that PWV increase
      is steeper after the fifth decade. Recent follow-up studies showed decrease of
      arterial stiffness during the first year after kidney transplantation (KTx). This
      study aimed to investigate PWV change in kidney transplant recipients (KTR)
      during long-term follow-up. MATERIAL/METHODS: Carotid-femoral PWV was measured at
      baseline (PWV1) and then after at least 24 months (range 24-34, mean +/-SD 28+/
      3) of follow-up (PWV2) in 61 KTR aged 46+/-12 years. Baseline PWV measurements
      were performed at 36+/-27 months (range 4-121) after KTx. Clinical and laboratory
      data were also analyzed. GFR was calculated with MDRD formula (eGFR). ?PWV was
      calculated as (PWV2-PWV1)/PWV1. RESULTS: Significant increase in PWV (9.1+/-1.7
      vs. 9.8+/-2.0; p<0.002) and pulse pressure (PP) (50+/-11 vs. 53+/-14; p<0.05) was
      found during follow-up, but systolic, diastolic and mean arterial pressure did
      not change. eGFR did not change during follow-up (55+/-16 vs. 56+/-16 ml/min/1.73
      m2). PWV increase was observed in patients aged >=50 years (9.8+/-1.8 vs. 10.8+/
      1.9; p<0.01), while not in younger patients (8.5+/-1.5 vs. 8.9+/-1.5; p=0.14).
      Significant positive correlation was found between ?PWV and duration of the
      follow-up period. CONCLUSIONS: The study revealed progressive arterial stiffening
      in kidney transplant recipients during long-term follow-up. Further studies are
      necessary to explain the pathophysiology of this phenomenon.

PMID- 21959508
TI  - Intra-abdominal infections after simultaneous pancreas - kidney transplantation.
AB  - BACKGROUND: Intra-abdominal infections (IAI) are among the most common causes of
      pancreatic graft loss and recipient death in the early period after simultaneous
      pancreas - kidney transplantation (SPK). The aim of the study was to analyze risk
      factors and clinical consequences of IAI in SPK patients. MATERIAL/METHODS: Forty
      six consecutive SPK performed from 2004 to 2010 were subjected to analysis.
      RESULTS: IAI developed in 10 recipients (21.7%). The group of recipients with IAI
      had a higher rate of patients that required transfusion of more than 2 blood
      units (90% vs. 47%, p=0.028) or relaparotomy (80% vs. 14%, p<0.001), in
      comparison with patients without IAI. Additionally, in patients with IAI, both
      delayed kidney graft function or primary kidney graft nonfunction (40% vs. 11%,
      p=0.001) and recipient death (40% vs. 3%, p=0.006) were more frequently observed.
      Logistic regression analysis revealed an increased risk of IAI development in
      patients who required early relaparotomy (OR=24.8, p<0.001), transfusion of more
      than 2 blood units (OR=12.6, p=0.02), or postoperative dialysis therapy (OR=14.1,
      p=0.003). CONCLUSIONS: Perioperative blood loss requiring transfusion and
      necessity of relaparotomy increase the risk of IAI after SPK. Development of IAI
      after SPK may result in impaired kidney graft function and increases patient
      mortality in the early postoperative period.

PMID- 21959509
TI  - Two decades of experience in mucormycosis after kidney transplantation.
AB  - BACKGROUND: Invasive mucormycosis is a very rare infection after kidney
      transplantation. Here, we report 25 renal transplant recipients with
      mucormycosis; to our knowledge, this is the largest reported population of
      mucormycosis in these patients. MATERIAL/METHODS: In a retrospective study, we
      collected all kidney transplants with mucormycosis from 9 Transplant Centers of
      Iran from 1990 to 2010. The definitive diagnosis of mucormycosis was established
      by obtaining a biopsy specimen of the involved tissue. RESULTS: The most form of
      disease was rhino-cerebral (n =13), followed by pulmonary (n=7). Overall
      mortality rate was 52% (n=13), particularly in recipients with pulmonary
      infection (100%); however, the mortality rate in rhino-cerebral form of disease
      was low (30.8%). There was no statistically significant difference in mortality
      rate between male and female (P=0.8). In addition, no significant differences
      were seen in mortality rate with age of patients (p=0.8) and time of diagnosis
      since transplantation (p=0.3). Pulmonary infection was more seen in recipients
      received azathioprine compared to those on mycophenolate mofetil (p=0.006).
      CONCLUSIONS: Mucormycosis after renal transplantation has a poor prognosis,
      particularly patients with pulmonary involvement.

PMID- 21959511
TI  - Aldehyde dehydrogenase (ALDH) - a promising new candidate for use in preclinical
      and clinical selection of pluripotent very small embryonic-like stem cells (VSEL
      SCs) of high long-term repopulating hematopoietic potential.
AB  - BACKGROUND: In the field of stem cells (SCs) biology there is great need for a
      universal marker that can effectively identify the rare populations of SCs in
      order to characterize and isolate them for research and therapeutic purposes. In
      line with this idea, the measurement of aldehyde dehydrogenase (ALDH) activity
      shows promising potential as a common marker for the identification of SCs.
      Recently discovered very small embryonic-like stem cells (VSEL SCs) have a
      pluripotent nature and high long-term repopulating hematopoietic potential. The
      aim of the present study was to determine whether VSEL SCs isolated from
      umbilical cord blood (CB) and different murine organs express high ALDH activity.
      MATERIAL/METHODS: To address this issue, 12 CB units were analyzed by employing
      flow cytometry to detect the following populations: (i) CXCR4(+)/Lin(-)/CD45(
      )/ALDH(high), (ii) CD34(+)/Lin(-)/CD45(-)/ALDH(high) and (iii) CD133(+)/Lin(
      )/CD45(-)/ALDH(high). Additionally, selected organs from 16 5-week-old female
      inbred C57BL/6J mice and 16 7-month-old female C57BL/6J mice were analyzed for
      detection of the following populations: (i) Sca-1(+)/Lin(-)/CD45(-) and (ii) Sca
      1(+)/Lin(-)/CD45(+). All these populations were assessed for ALDH activity.
      RESULTS: We found that CB contains VSEL SCs with high ALDH activity. We also
      observed that ALDH(high) cells constitute a modest percentage of VSEL SCs present
      in selected murine organs. CONCLUSIONS: We demonstrated that CB and adult murine
      organs possess a subpopulation of ALDH(high) VSEL SCs. Above all, the observed
      high level of ALDH activity can be considered a functional marker of organ
      derived pluripotent SCs and allows for simple, efficient isolation of cells with
      primitive features for their utility in targeted cell therapies.

PMID- 21959510
TI  - The culture of temporary tumor-like bone marrow mesenchymal stem cells (TT-BMSC)
      and the detection of cell biology property.
AB  - BACKGROUND: Bone marrow mesenchymal stem cells (BMSC) are common seed cells for
      transplantation. However, there are some limitations in their use that have not
      yet been resolved. Our research modified tumor-related genes temporarily on BMSC
      which simulated tumorigenesis temporarily in vitro. The cells were named
      temporarily tumor-like bone marrow mesenchymal stem cells (TT-BMSC).
      MATERIAL/METHODS: Cultivation of TT-BMSC: BMSC were cultured and identified, then
      the BMSC were transfected MMP-2 gene expressive vector and screened for 4 weeks
      by G418. Finally, the anti-oncogene PTEN of BMSC was knockdown by ribonucleic
      acid interference (RNAi) using PTEN gene special small interfering ribonucleic
      acid (SiRNA). The detection cell biology property of TT-BMSC in vitro: Methyl
      thiazolyl tetrazolium (MTT) assay and Cell cycle analysis for cell proliferation,
      Matrigel Invasion Assay for invasion and migration, and the cell model of
      ischemia and anoxia in vitro for survival. RESULTS: RT-PCR and Western blot
      results indicated MMP-2 expression increase significantly after transfection of
      the MMP-2 expressive vector in the BMSC, while PTEN mRNA and protein expression
      decrease significantly after PTEN RNAi, and the longest duration of the PTEN RNAi
      is 15 days. MTT assay and Cell cycle analysis indicated TT-BMSC cell growth vigor
      is reinforced significantly (P<0.001). Matrigel Invasion Assay showed that TT
      BMSC can go through the matrigel successfully (P<0.001). The ability of TT-BMSC
      to tolerate ischemia and anoxia increased significantly in the model of ischemia
      and anoxia in vitro (P<0.001). CONCLUSIONS: We cultivated TT-BMSC successfully
      and TT-BMSC possessed a powerful ability to survive, proliferate, invade and
      migrate in vitro.

PMID- 21959513
TI  - Do thyroid disorders affect the postoperative course of patients in the early
      post-heart transplant period?
AB  - BACKGROUND: Thyroid hormones are essential for the correct functioning of the
      entire body. Diagnosis of thyroid disorders in patients after heart transplant in
      the early post-operative period and the implementation of correct treatment may
      prevent life-threatening complications. MATERIAL/METHODS: The aim of the study
      was to determine whether the complicated postoperative course (ie,
      hypothyroidism, hyperthyroidism or low fT3 syndrome) in patients in the first
      month after heart transplantation was connected with impaired thyroid hormone
      management. The analysis encompassed material from 98 patients treated with heart
      transplantation between February 9, 2004 and January 4, 2010. Hyperthyroidism was
      diagnosed in 21 patients (19M/2F, 52+/-7 years of age), hypothyroidism in was
      diagnosed in 13 patients (10M/3F, 46+/-12 years old), and low fT3 syndrome was
      diagnosed in 18 patients (14M/4F, 43+/-12 years old). RESULTS: Patients with fT3
      syndrome had the highest mortality (16.7%, NS), highest incidence of acute
      rejection (38.9%, NS), highest number of reoperations (27.8%, NS), and highest
      incidence of bacterial (16.7%, NS) and fungal infections (11.1%, NS).
      Cytomegaloviral infections occurred most frequently in patients with
      hyperthyroidism (23.8%, NS). Patients with hypothyroidism (84.6%, NS) were
      hospitalized the longest (>30 days), had the highest tendency towards pleural
      effusion (23.1%, NS) and pericardial effusion with tamponade (15.5%, NS),
      bradycardia with pacemaker (15.4%, NS) and renal failure requiring
      hemodiafiltration (15.4%, NS) (Table 1). CONCLUSIONS: 1. The thyroid test panel
      should be performed in all patients in the early post-heart transplant period. 2.
      The diagnosis of thyroid disorders should be immediately followed by correct
      treatment aimed at restoring the euthyroid state, with a view to facilitate
      recovery and rehabilitation as well as to shorten the hospitalization time,
      thereby lowering treatment costs.<br />

PMID- 21959512
TI  - Association of the rs10918594 of nitric oxide synthase 1 adaptor protein (NOS1AP)
      polymorphisms with the graft function after kidney transplantation.
AB  - BACKGROUND: The purpose of this study was to investigate the relationship of
      nitric oxide synthase 1 adaptor protein (NOS1AP) polymorphism with serum
      creatinine level and occurrence of delayed graft function (DGF) in kidney
      transplant recipients. MATERIAL/METHODS: This prospective observational study
      included 75 kidney transplantations. The data from 40 kidney donors (8 females,
      32 males) included sex, age, and cause of death. Donors fully met multi-organ
      transplantation criteria. Recipient data included sex, age, cause of renal
      insufficiency, and time and number of hemodialyses prior to transplantation.
      Applying polymerase chain reaction restriction fragments length polymorphism
      method, we investigated rs10918594 NOS1AP polymorphism among the 75 kidney
      recipients. The function of every transplanted kidney was correlated with this
      polymorphism. We defined DGF as requirement for at least 1 hemodialysis after
      kidney transplantation. We investigated the association of NOS1AP polymorphism
      with the recipient serum creatinine levels at day 1 and 180 days after kidney
      transplantation and the occurrence of DGF. RESULTS: The analysis of variance
      showed higher serum creatinine levels in kidney recipients with GG genotype
      compared with the CC_CG genotype at day 1 and at day 180 post-transplantation.
      Occurrence of DGF in the post-operative period in kidney recipients with the
      variant genotypes CG compared with the GG_CC genotype was higher, although these
      differences were no statistically significant. CONCLUSIONS: Our data suggests no
      statistically significant association of the rs10918594 polymorphism of nitric
      oxide synthase 1 adaptor protein (NOS1AP) with the graft function after kidney
      transplantation.

PMID- 21959514
TI  - Complications of ureterovesical anastomosis in adult renal transplantation:
      comparison of the Lich-Gregoire and the Taguchi techniques.
AB  - BACKGROUND: Our aim is to identify the incidence of urologic complications in
      adult renal transplantation comparing two different ureterovesical anastomosis
      techniques, the Taguchi (T) and Lich-Gregoire (LG). MATERIAL/METHODS:
      Retrospective analysis of adult renal transplants performed at the MUHC between
      2000-2009. Excluded: multi-organ transplants, re-do transplants, variant ureteric
      anastomosis and patients received grafts from UNOS ECD. 372 patients were
      analyzed. 209 patients (56%) in the T group and 163 patients (44%) in the LG
      group. Fisher's exact test was used to compare the groups for urologic
      complications. A multivariate analysis was performed to identify factors
      associated with graft rejection and death. RESULTS: 21 patients developed a
      urinary leak or stricture. A total of 13 patients (3.4%) developed ureteric
      strictures and 9 (2.4%) patients developed urinary leak with no difference in
      urinary leak or stricture between both groups (p=1). Hematuria requiring
      intervention developed in 55 patients. A higher incidence of complicated
      hematuria in the T group when compared to the LG group (37 vs. 18, p=0.079)). No
      differences in other ureteric complications between the 2 groups. Delayed graft
      function OR=3.4 (95% CI=1.8-6.3) and grafts from a deceased donors OR=2.2 (95%
      CI=1.1-4.5) are factors associated with graft loss. Factors associated with first
      episode of rejection include delayed graft function OR=2.4 (95% CI=1.3-4.4), and
      the development of ureteric stricture OR=3.9 (95% CI=1.8-8.7). CONCLUSIONS: Both
      techniques can be used interchangeably for adult renal transplantation. T
      technique is associated with a greater risk of hematuria. Ureteric strictures are
      associated with a shorter time to first graft rejection.

PMID- 21959515
TI  - Preoperative pulmonary evaluation of liver transplant candidates: results from
      341 adult patients.
AB  - BACKGROUND: Pulmonary disorders are among the commonly encountered and
      prognostically important problems in patients with chronic liver disease. To
      define the prevalence and types of respiratory disorders in patients with
      advanced liver disease evaluated for liver transplant (LT) candidacy, and to
      determine factors affecting postoperative outcome. MATERIAL/METHODS: The records
      of 341 adult patients evaluated for LT candidacy were retrospectively examined.
      Demographic, clinical and laboratory data including chest X-ray, spirometry and
      echocardiography results were collected. Postoperative pulmonary complications
      and mortality rates were determined. RESULTS: With a mean age of 45.1 years, 73
      (21.4%) patients presented with respiratory symptoms or signs. The most common
      radiographic abnormality on chest X-ray was right diaphragm elevation (53.2%).
      Hypoxemia was detected in 38.1% of the patients. Pulmonary hypertension was
      detected in 100 of 327 (30.6%) patients on Doppler echocardiography. There were
      141 patients who underwent surgery. Postoperative pulmonary complications
      developed in 60 patients, with pneumonia being the most prevalent complication
      (n=28). Smoking, emphysema, abnormal spirometry, pulmonary hypertension, hypoxia
      and orthodeoxia were found to be factors associated with increased postoperative
      pulmonary complications (P<0.05 for all). Mortality rate was 24.1% (n=34) and
      found to be significantly higher in patients who developed a postoperative
      complication than in those who did not (38.7% vs. 13.8%, respectively; p=0.001).
      CONCLUSIONS: The authors' findings indicate that pulmonary disorders impact
      prognosis and are common in patients evaluated for LT candidacy. Postoperative
      pulmonary complication is one of the major factors affecting mortality.
      Therefore, in order to increase the success of the transplant operation, a
      thorough preoperative pulmonary evaluation is of paramount importance.

PMID- 21959516
TI  - Reduction of oedema formation after preconditioning with dopamine in an isolated
      rat lung model is mediated by adrenergic receptors.
AB  - BACKGROUND: Donor treatment with dopamine (DA) is an effective modality to
      improve organ quality by reduction of hypothermic, ischemic and reperfusion (I/R)
      injury. It is unknown by which mechanism DA reduces oedema formation and
      inflammation. Therefore we tested the first time in an isolated rat lung model if
      dopaminergic or adrenergic receptors are involved. MATERIAL/METHODS: Rats were
      treated for 1 hr with NaCl, DA or simultaneously with DA alpha- beta- D1- or D2
      receptor blockers. Thereafter lungs were explanted, flushed with Perfadex
      solution and stored at 4 degrees C. Peak inspiratory pressure (PIP), pulmonary
      arterial pressure (PAP) and lung weight were measured during reperfusion of 3
      hrs. Inflammatory mediators and the expression of adhesion molecules were
      measured after perfusion. RESULTS: Up to 6 hours of hypothermia did not influence
      oedema formation or PIP and PAP during reperfusion time. However, hypothermia
      after 8 hrs significantly increased PIP, PAP and pulmonary oedema in NaCl, alpha-
      and beta-blocker treated lungs, but significantly not in DA, D1- or D2-blocker
      treated lungs. Perfusion and ventilation alone induced a strong upregulation of
      cytokine-induced neutrophil chemoattractant-1 and adhesion molecules in
      untreated, alpha- and beta-blocker treated lungs, while in DA, D1- and D2-blocker
      treated lungs significant lower levels were found. CONCLUSIONS: Our study
      suggests that dopamine mediated protective effects on I/R damage and inflammation
      in donor lungs are most likely mediated via adrenergic receptors. These findings
      are highly relevant because new strategies for organ preservation are necessary
      in terms of long donation waiting lists.

PMID- 21959517
TI  - The effect of preservation solutions UW and EC on the expression of renin I,
      angiotensinogen and angiotensin I-converting enzyme genes in rat kidney.
AB  - BACKGROUND: Ischemia/reperfusion injury in organ transplantation is a multifactor
      process that may lead to delayed graft function (DGF), and has a significant
      impact on short- and long-term graft survival. The activation of the renin
      angiotensin system may be important in the pathophysiology of DGF. Preservation
      solutions are thought to diminish the ischemic injury, and appropriate choice of
      the solution should contribute to improved graft function and better prognosis
      for graft survival. The aim of this study was to examine the effect of
      preservation solutions UW and EC on the expression of renin I, angiotensinogen
      and angiotensin I-converting enzyme genes in rat kidney. MATERIAL/METHODS: The
      study was carried out on Wistar rat kidneys divided into 3 groups: kidneys
      perfused with 0.9% NaCl (control group), with UW preservation solution, and with
      EC preservation solution. We investigated the expressions of renin I,
      angiotensinogen- and angiotensin I-converting enzyme genes in kidneys perfused
      with EC and UW solutions after 12 min (minutes) and 24 h (hours) of cold ischemia
      and 30 min of warm ischemia. RESULTS: The perfusion with UW and EC solution
      caused an increase of renin I, angiotensinogen and angiotensin I-converting
      enzyme genes expression in kidneys. This increase was enhanced in kidneys
      perfused with UW solution in comparison with kidneys perfused with EC solution.
      The 24 h preservation with UW solution resulted in a decrease of renin
      angiotensin activity increased in cold ischemia. CONCLUSIONS: UW preservation of
      24 h decreased renin-angiotensin system activity activated in cold ischemia but
      not in warm ischemia.

PMID- 21959518
TI  - Effect of zinc on early graft failure following intraportal islet transplantation
      in rat recipients.
AB  - BACKGROUND: Zinc (Zn) is related to insulin synthesis, storage and secretion. Zn
      status in patients with Type 1 diabetes is significantly lower than in healthy
      controls. Intraportal islet transplantation (IPIT) is a radical treatment for
      diabetes, the success of which depends largely on the survival of the
      transplanted islets. This study demonstrates the impact of a Zn-rich environment
      on transplanted islet survival. MATERIAL/METHODS: Diabetic Wistar rats were
      transplanted with syngeneic islets. Rats in the high-Zn-diet group were fed a
      standard pelleted diet containing ZnSO4 at 1000 ppm, whereas those in the control
      group were fed an ordinary diet alone (ZnSO4 at 50 ppm) for two weeks prior to
      islet transplantation. We examined Zn level of plasma, the blood glucose levels,
      and histological findings, etc., after intraportal islet transplantation.
      RESULTS: The high-Zn-diet group showed excellent blood glucose control compared
      with the control group on observation days 3, (237.1+/-120.6 mg/dl vs. 164.2+/
      69.1 mg/dl; p<0.05) and 14, (273.7+/-160.9 mg/dl vs. 179.2+/-114.3 mg/dl;
      p<0.05). Early graft failure was found to be suppressed in the high-Zn-diet group
      on day 3 after transplantation (6.7% vs. 33.3%: p<0.05). As for the percentage of
      granulated islets, the high-Zn-diet group was improved (65.1% vs. 41.8%: p<0.05).
      CONCLUSIONS: These results indicated that a zinc-rich environment is advantageous
      for the recipient in intraportal islet transplantation. Zn is harmless in humans;
      thus, we consider that Zn supplementation could be a simple way to improve
      clinical results of intraportal islet transplantation.

PMID- 21959519
TI  - Polypropylene mesh repair of incisional hernia after kidney transplantation:
      single-center experience and review of the literature.
AB  - BACKGROUND: Incisional hernia after kidney transplantation increases patient
      morbidity and impacts quality of life. Reports of hernia mesh repair after kidney
      transplantation are rare; thus, the benefit of mesh hernioplasty in transplanted
      patients is assumed. However, it is also assumed that transplant patients are
      susceptible to incisional and mesh infections. MATERIAL/METHODS: Between January
      1, 2005 and December 31, 2010, we performed 1067 kidney transplantations. Twenty
      eight patients developed incisional hernias (2.6%), and mesh repair was performed
      in 20 of them (8 women, 12 men; median age 59.5 years, range 43 to 68 years). We
      retrospectively studied this latter group. We also reviewed the literature
      regarding the results of this treatment. RESULTS: Postoperative mortality was
      zero, but postoperative wound bleeding led to surgical revision in 1 patient.
      Wound infection did not occur. During the follow-up period we observed 4 hernia
      recurrences (20%). CONCLUSIONS: In conclusion, our retrospective study and review
      of the literature confirmed the safety and low incidence (1.1% to 3.8%) of mesh
      hernia repair in chronic immunosuppressed patients after renal transplantation,
      which has a minimal risk of wound infection and no higher risk of hernia
      recurrence than in non-transplant patients.

PMID- 21959520
TI  - Physical activity long-term after liver transplantation yields better quality of
      life.
AB  - BACKGROUND: Transplantation is the only effective method of treatment for end
      stage and acute liver failure. Increased average survival time has been observed,
      and results from improved surgical technique and amended immunosuppression
      protocols. However, longer survival of patients after orthotopic liver
      transplantation (OLT) results in higher rate of various complications and
      ailments (eg, chronic fatigue, anxiousness, social isolation). Hence, gradual
      deterioration of health-related quality of life (HRQoL) is likely. The goal of
      this study was to examine the relation between physical activity and quality of
      life in patients 5 years after OLT. MATERIAL/METHODS: Twenty-six randomly
      selected patients who survived more than 5 years after orthotopic liver
      transplantation were included into the study. An SF-36 questionnaire was used for
      assessment of quality of life. Physical activity was measured subjectively by
      characterizing its type, duration and frequency per week during the previous 12
      months. Patients were divided into 2 groups according to the results of physical
      activity assessment. Group A consisted of patients who had indicated they had a
      sedentary life style, and group B of those regularly engaging in physical
      exercise. RESULTS: Results of the SF-36 questionnaire in 10 categories were
      compared between the 2 groups. The majority of aspects of health-related quality
      of life (physical function, body problems, general health, social function, and
      emotional reaction) were significantly improved in patients who indicated they
      regularly engaged in physical exercise. CONCLUSIONS: Better quality of life was
      observed in patients who were physically active after OLT. Improving life quality
      with regular physical activity could be a valuable supplementation of complex
      management of OLT recipients.

PMID- 21959521
TI  - Ezetimibe in sirolimus-associated hyperlipidemia: to add or not to add to
      statins?
AB  - BACKGROUND: Hyperlipidemia is a universal adverse effect of proliferation signal
      inhibitors (PSI). We report our experience with ezetimibe/statin combined therapy
      in a case of a kidney transplant recipient receiving sirolimus (SRL)-based
      immunosuppression. We also present our doubts concerning the need for ezetimibe
      in kidney transplant recipients on PSI-based immunosuppression. CASE REPORT:
      Results. In the reported patient, ezetimibe/statin combination therapy
      successfully decreased cholesterol level. CONCLUSIONS: Combined therapy with
      ezetimibe and statin seems to be effective and safe in transplant recipients with
      SRL-associated hyperlipidemia. However, well-designed clinical trials should be
      performed to evaluate if there is an impact of such treatment on the frequency of
      cardiovascular events and patient survival.

PMID- 21959522
TI  - Durable remission in a patient with refractory subcutaneous panniculitis-like T
      cell lymphoma relapse after allogeneic hematopoietic stem cell transplantation
      through withdrawal of cyclosporine.
AB  - BACKGROUND: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is an uncommon
      subtype of peripheral T-cell lymphoma and its standard treatment remains ongoing
      study. Cases refractory to chemotherapy are suggested to benefit from autologous
      hematopoietic stem cell transplantation (auto-HSCT). Nevertheless, post auto-HSCT
      recurrence seems to be irreversible. Very few cases of allogeneic-HSCT (allo
      HSCT) in SPTCL have been reported so far. CASE REPORT: A 27-year-old female
      presented to our hospital with refractory SPTCL for receiving auto-HSCT.
      Cutaneous biopsy had confirmed diagnosis of SPTCL at a local hospital, where 5
      lines and 10 cycles of intensive chemotherapy had been prescribed. All these
      treatment provided marginal control of disease progression. After her enrollment
      at our institute, she relapsed again after the collection of peripheral
      hematopoietic stem cells. Then, we performed an allo-HSCT to her from a 10/10
      matched unrelated donor. Neutrophil and platelet engraftment occurred at day +11
      and +13, respectively. At day +15, lymphoma, however, came back, resulting in the
      withdrawal of cyclosporine from day +35 to day +75, when acute graft versus host
      disease (aGvHD) emerged. Lymphoma cells were observed in a subcutaneous biopsy
      from her leg. Eventually, skin manifestation of extensive chronic GvHD developed.
      By present, the patient has sustained complete remission for 18 months.
      CONCLUSIONS: Allo-HSCT is rational for patients with refractory SPTCL. To our
      knowledge, this is the first case, with regained remission after post allo-HSCT
      relapse through cyclosporine withdrawal, showing the existence of graft versus
      lymphoma (GvL) effect in SPTCL.

PMID- 21959523
TI  - Central pontine myelinolysis (CPM) associated with tacrolimus (FK506) after liver
      transplantation.
AB  - BACKGROUND: Central pontine myelinolysis (CPM) is the most detrimental neurologic
      complication after liver transplantation. The incidence of CPM after liver
      transplantation ascends to 17%. Although the precise etiology and pathogenesis of
      CPM is largely unknown, a growing literature implicates a possible role of
      immunosuppressive agents, such as Cyclosporine (incidence 30%) on its
      development. Other immunosuppressive agents also can cause CPM but the frequency
      of these cases is less compared to Cyclosporine. There is only one case report
      for Tacrolimus (FK506)-associated speech disorder, which might be an atypical
      presentation of CPM, and no case reports for Rapamycin. We present a case of
      Tacrolimus induced CPM. CASE REPORT: A 62-year-old woman who underwent liver
      transplantation developed clinical symptoms with radiologic evidence consistent
      with CPM 7 days after liver transplant. Since the electrolytes in this patient
      remained normal from her admission, the hypothesis of inmunossupressor
      neurotoxicity was established and the therapy was switched, resulting in an
      evident clinical and radiological improvement of her condition in the following
      days. Five months later, the patient's only neurological deficit was slight
      dysarthria and a follow-up MRI showed no abnormalities. CONCLUSIONS: This case
      provides evidence of Tacrolimus-associated CPM after transplantation, which
      presented with a classic "lock-in syndrome" with radiographic confirmation.

PMID- 21959524
TI  - Fulminant septic shock due to Clostridium perfringens skin and soft tissue
      infection eight years after liver transplantation.
AB  - BACKGROUND: Bacterial and fungal infections are the main cause of death within
      the first year after liver transplantation. Clostridium perfringens is the most
      common germ causing gas gangrene. Infections with Clostridium perfringens may
      present in a variety of clinical manifestations, reaching from asymptomatic
      infections to massive intravascular haemolysis and multiple organ failure due to
      septic shock. CASE REPORT: We here report on a 55-year old male liver transplant
      patient suffering from skin and soft tissue infection eight years after liver
      transplantation. The patient was referred to our department from a community
      hospital. Upon admission in our department the infection had been ongoing for at
      least three days. Laboratory analyses demonstrated severe infection and impaired
      liver function. Tomogram and computed tomography scan of his right limb showed
      typical images of gas gangrene. The patient was immediately scheduled for
      surgical debridement. During surgery the patient developed septic shock with
      severe coagulopathy and died six hours after the operation due to uncontrolled
      septic shock. The histopathological and microbiologic work-up of the resected
      skin and soft tissue showed necrotic areas infiltrated with Clostridium
      perfringens. CONCLUSIONS: Even long-term survivors of liver transplantation are
      at major risk for life-threatening infections. The reported clinical scenario of
      Clostridium perfringens infection indicates the narrow therapeutic window.
      Clostridium perfringens should always be considered as a cause of infection in
      liver transplant patients.

PMID- 21959525
TI  - Abdominal aortic aneurysms (AAA) post heart transplantation: a systematic review
      of literature.
AB  - Peripheral vascular disease is highly prevalent post heart transplantation (HTx).
      The prevalence of abdominal aortic aneurysms (AAA) post HTx ranges from 1.1-10%.
      We performed a Pub Med, EMBASE and Cochrane review search to identify articles on
      AAA post HTx. Data gathered from published data included: risk factors,
      progression of the aneurysm and clinical outcomes. Five studies were included in
      the systematic review. Baseline demographic data, clinical characteristics, data
      on AAA prevalence and characteristics, the treatment strategies and follow up
      were extracted from each of these studies. Our systematic review showed that the
      prevalence of AAA post HTx ranged from 2-10% in the retrospective studies and
      6.5% in a single prospective study. Rupture rates during a follow up period
      ranged from 11-38% and during that time period the mean aneurysmal expansion rate
      ranged from 0.78+/-0.41 cm/yr to 1.2+/-0.4 cm/yr. Male gender, ischemic heart
      disease, corticosteroid use, smoking and improved hemodynamics and ejection
      fraction post HTx were reported as possible associated risk factors in the
      development of AAA. Open surgical management was the treatment of choice although
      endovascular treatment was used in a minority of patients. AAA is increasingly
      prevalent post HTx and may be associated with greater rupture and expansion
      rates. Meticulous follow up and further prospective clinical studies are
      warranted to determine risk factors, expansion rates and clinical outcomes.

PMID- 21959526
TI  - Exposure to bisphenol A appears to impair hippocampal neurogenesis and spatial
      learning and memory.
AB  - Bisphenol A (BPA) is widely used in the manufacture of plastics and epoxy resins,
      and is known to affect reproductive organ growth and development. However, the
      effects of BPA on hippocampal neurogenesis are unclear in young adult mice.
      Therefore, the present study was conducted to examine the effects of BPA on
      hippocampal neurogenesis and learning as well as memory performance in young
      adult mice. BPA (1, 5, and 20 mg/kg/day) was administered orally to mice for 2
      weeks. It was found that high-dose BPA (20 mg/kg/day) decreased the number of
      newly generated cells in hippocampus, but that low-dose BPA (1 mg/kg) increased
      the survival of newly generated cells in hippocampi of young mice. Furthermore,
      high-dose BPA (20mg/kg/day) was found to impair learning and memory performance
      significantly. However, no significant differences were observed between high-
      and low-dose treated mice in terms of levels of brain-derived neurotrophic factor
      (BDNF) or reactive oxygen species production in hippocampus. In addition, BPA
      treatment did not induce neuronal loss or damage or astrocyte activation. These
      data suggest that exposure to BPA causes fluctuations in hippocampal neurogenesis
      in young adult mice that result in spatial learning and memory impairment via a
      BDNF-independent pathway.

PMID- 21959527
TI  - Dietary antioxidant supplements: benefits of their combined use.
AB  - Several dietary supplements claim medicinal benefits due to their composition in
      hydrophilic and lipophilic molecules, natural extracts or synthetic compounds
      with antioxidant properties. In the present work, the antioxidant activity of
      selected supplements taken in pills, capsules or infusions were studied either
      individually or combined. Linear discriminant analysis (LDA) was used to
      categorize the condensed formulations (pills and capsules), infusion bags and
      combined samples according with their antioxidant activity measured by radical
      scavenging activity, reducing power and lipid peroxidation inhibition using brain
      homogenates as models. AAF proved to have the highest antioxidant activity in all
      the assayed methods, either singly taken or included in mixtures. Furthermore,
      the mixtures containing this supplement revealed synergistic effects in 92% of
      the cases. The intake of antioxidant mixtures might provide some additional
      benefits.

PMID- 21959528
TI  - Botanicals as medicinal food and their effects on drug metabolizing enzymes.
AB  - Botanicals fall under different regulations in different countries and are mostly
      consumed without the consultation of the healthcare professional. Over the last
      decade, utilization of herbal therapies has been extensively documented. The
      findings indicate the possibility of potential herb-drug interactions due to the
      concomitant administration of herbal extracts and prescription/over-the-counter
      drugs. Simultaneously, with the increasing public awareness and search for safer
      herbal remedies, the study on herbal-drug interactions has gained momentum
      through the study of drug metabolizing enzymes. Cytochrome P450 (CYP) inhibition
      or induction is probably the most common mechanism for the pharmacokinetic
      interactions of herbs and drugs. Any inhibition of CYP enzymes by herbal extracts
      may result in enhanced plasma and tissue concentration of drugs, leading to
      toxicity, while induction results in reduced drug concentration leading to
      decreased drug efficacy and treatment failure. Considering the rapidly growing
      herbal markets, these types of clinical interactions remain under-reported and
      unclear. With the increasing consumption of herbal extracts along with
      prescription medicines, the safety of herbs has become a concern. This article
      reviews the potential for drug interactions by herbal extracts through drug
      metabolizing enzymes.

PMID- 21959529
TI  - Effect of sweet grass extract against oxidative stress in rat liver and serum.
AB  - Ethanol metabolism is accompanied by generation of free radicals which can damage
      the cell components. However, sweet grass is a source of coumarin and its
      derivatives have emerged as a promising group of antioxidant compounds. The aim
      of this study has been to investigate the influence of sweet grass on oxidative
      stress formation in the liver and serum of rats intoxicated with ethanol. Alcohol
      intoxication led to a decrease in the superoxide dismutase, catalase, glutathione
      peroxidase and reductase activity in the blood serum as well as in the liver, but
      not in the glutathione reductase activity. The decrease in the antioxidant
      abilities of the examined tissues after ethanol intoxication resulted in enhanced
      lipid peroxidation measured as malondialdehyde and 4-hydroxynonenal levels. The
      metabolic consequence of oxidative modifications of lipids was damage of the
      liver cells membrane and an increase in its permeability appeared as a leakage of
      alanine aminotransferase and aspartate aminotransferase into the blood.
      Administration of sweet grass to the ethanol-intoxicated rats remarkably
      prevented the significant increase in concentrations of all measured lipid
      peroxidation products as well as the damage of the liver cell membrane. These
      results indicate beneficial antioxidant effect of the sweet grass on the liver of
      rats intoxicated with ethanol.

PMID- 21959531
TI  - Prevalence of pituitary adenomas in macroprolactinemic patients may be higher
      than it is presumed.
AB  - One form of prolactin (PRL) is macroprolactin with high molecular mass. Many
      macroprolactinemic patients have no pituitary adenomas and no clinical symptoms
      of hyperprolactinemia, it is controversial whether macroprolactinemia is a benign
      condition that does not need further investigation and treatment. In this study,
      we aimed to compare macroprolactinemic patients (group I) with the true
      hyperprolactinemic patients (group II) for the presence of pituitary adenoma. We
      investigated 161 patients with hyperprolactinemia, whose magnetic resonance
      imaging records of the pituitary were taken. All patients were questioned for
      irregular menses, infertility and examined for galactorrhea. Patients were
      screened for macroprolactinemia by polyethylene glycol precipitation, and a
      recovery of <=40% and normal monomeric PRL level was taken as an indication of
      significant macroprolactinemia. Of 161 patients with hyperprolactinemia, 60
      (37.26%) had macroprolactinemia. PRL levels of group II were lower than those of
      group I (P = 0.011), although monomeric PRL levels of group II were higher than
      those of group I (P = 0.0005). Of 60 macroprolactinemic patients, 16 (26.7%) had
      pituitary adenomas. The prevalence of pituitary adenomas was lower in group I,
      compared with group II (P = 0.0005). No significant differences were found
      between the prevalences of irregular menses and infertility of group I and II (P
      = 0.084, P = 0.361). Prevalence of galactorrhea in group I was lower than that in
      group II (P = 0.048). Prevalence of pituitary adenomas in macroprolactinemic
      patients is lower compared with the true hyperprolactinemic patients, but may be
      higher than that found in other recent studies and in the general population.

PMID- 21959532
TI  - Simultaneous targeting of PI3K and mTOR with NVP-BGT226 is highly effective in
      multiple myeloma.
AB  - Multiple myeloma is still uncurable. Myeloma cells become resistant to common
      drugs and patients eventually die of tumour progression. Therefore, new targets
      and drugs are urgently needed. NVP-BGT226 is a novel, orally bioavailable small
      molecule inhibitor of phosphoinositol-3-kinase and mammalian target of rapamycin.
      Here, we show that NVP-BGT226 inhibits growth in common myeloma cell lines and
      primary myeloma cells at nanomolar concentrations in a time-dependent and dose
      dependent manner. Western blots for the detection of caspase 3 cleavage and
      annexin-V-fluorescein isothiocyanate/propidium iodide assays revealed induction
      of apoptosis in common myeloma cells lines. Induction of apoptosis was
      accompanied by upregulation of proapoptotic Bim and a moderate upregulation of
      Mcl-1 and Bad and a downregulation of Bcl-2, Bax and Bcl-Xl. Inhibition of cell
      growth was mainly due to inhibition of myeloma cell proliferation, as shown by
      the 5-bromo-2'-deoxyuridine assay. Cell cycle analysis revealed induction of cell
      cycle arrest in the G1 phase, which was due to downregulation of cyclin D1,
      cyclin D2, pRb and cdc25a. NVP-BGT226 inhibited phosphorylation of protein kinase
      B (Akt), P70S6k and 4E-BP-1 in a time-dependent and dose-dependent manner.
      Furthermore, we show that the stimulatory effect of insulin-like growth factor 1,
      interleukin-6 and conditioned medium of HS-5 stromal cells on myeloma cell growth
      is completely abrogated by NVP-BGT226. Overall, inhibition of phosphoinositol-3
      kinase/mammalian target of rapamycin by NVP-BGT226 is highly effective, and NVP
      BGT226 represents a potential new candidate for targeted therapy in multiple
      myeloma.

PMID- 21959533
TI  - ESPR's Total Environment.

PMID- 21959534
TI  - Biological Activity in a Heavily Organohalogen-Contaminated River Sediment (8
      pp).
AB  - BACKGROUND, AIMS AND SCOPE: Sediments of the Spittelwasser creek are highly
      polluted with organic compounds and heavy metals due to the discharge of
      untreated waste waters from the industrial region of Bitterfeld-Wolfen, Germany
      over the course of more than one century. However, relatively few data have been
      published about the chloroorganic contamination of the sediment. This paper
      reports on the content of different (chloro)organic compounds with special
      emphasis on polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F), and
      chlorobenzenes. Existing concepts for the remediation of Spittelwasser sediment
      include the investigation of natural attenuation processes, which largely depend
      on the presence of an intact microbial food web. In order to gain more insight in
      terms of biological activity, we analyzed the capacity of sediment microflora to
      degrade organic matter by measuring the activities of extracellular hydrolytic
      enzymes involved in the biogeochemical cycling of carbon, nitrogen, phosphorus
      and sulfur. Furthermore, the detection of physiologically active bacteria in the
      sediment, particularly of those known for their capability to reductively
      dehalogenate organochlorine compounds, illustrates the potential for intrinsic
      bioremediation processes. METHODS: PCDD/F and chlorobenzenes were analyzed by gas
      chromatography(GC)/mass spectrometry and GC/flame ionization detection,
      respectively. The activities of hydrolytic enzymes were determined from freshly
      sampled sediment layers using 4-methylumbelliferyl (MUF) or 7-amino-4
      methylcoumarin-conjugated model compounds and kinetic fluorescence measurements.
      Physiologically active bacteria from different sediment layers were
      microscopically visualized by fluorescence in situ hybridization (FISH). Specific
      bacteria were identified by 16S rRNA gene amplification and sequencing. RESULTS
      AND DISCUSSION: The PCDD/F congener profile was dominated by dibenzofurans. In
      addition, the presence of specific tetra and pentachlorinated dibenzofurans
      supported the assumption that extensive magnesium production was one possible
      source for the high contamination. A range of other chloroorganic compounds,
      including several isomers of chlorobenzenes, hexachlorocyclohexane and 1,1,1
      trichloro-2,2-bis (p-chlorophenyl)ethane (DDT), was present in the sediment.
      Activities of extracellular hydrolytic enzymes showed a strong decrease in those
      sediment layers that were characterized by high contents of absorbable organic
      halogen (AOX), indicating disturbed organic matter decay. Interestingly, an
      abnormal increase of cellulolytic enzyme activities below the organochlorine-rich
      layers was observed, possibly caused by residual cellulose from discharges of
      sulfite pulping wastes. FISH revealed physiologically active bacteria in most
      sediment layers from the surface down to the depth of about 60 cm, including
      members of Desulfitobacterium (D.) and Sulfurospirillum. The presence of D.
      dehalogenans was confirmed by its partial 16S rRNA gene sequence. CONCLUSION:
      Results of chemical sediment analyses demonstrated high loads of organochlorine
      compounds, particularly of PCDD/F. Several years after stopping the waste water
      discharge to Spittelwasser creek, this sediment remains a main source for
      pollution of the downstream river system by way of the ongoing mobilization of
      sediment during high floods. As indicated by our enzyme activity measurements,
      the decomposition potential for organic matter is low in organochlorine-rich
      sediment layers. In contrast, the comparably higher enzyme activities in less
      organochlorine-polluted sediment layers as well as the presence of
      physiologically active bacteria suggest a considerable potential for natural
      attenuation. RECOMMENDATIONS AND PERSPECTIVE: . From our data we strongly
      recommend to explore the degradative capacity of sediment microorganisms and the
      limits for in situ activity towards specific sediment pollutants in more detail.
      This will give a sound basis for the integration of bioremediation approaches
      into general concepts to reduce the risk that permanently radiates from this
      highly contaminated sediment.

PMID- 21959535
TI  - Differential Sensitivity of a Coccal Green Algal and a Cyanobacterial Species to
      Dissolved Natural Organic Matter (NOM) (8 pp).
AB  - BACKGROUND: and Aim. In non-eutrophicated freshwaters, humic substances (HS) pose
      chemical stresses on aquatic organisms and, hence, separating sensitive from less
      sensitive or even tolerant species. One of the stresses, identified so far, is
      the reduction of photosynthetic oxygen production and reduction in growth in
      freshwater macrophytes and algae. In a previous paper, it has been shown that
      even closely related coccal green algae responded differently upon identical
      stress by HS, which is consistent with the hypothesis above. Due to their much
      simpler cellular ultrastructure, cyanobacteria are supposed to be more sensitive
      to HS exposure than eukaryote should be. One coccal green algal species
      (Desmodesmus communis) and one cyanobacterium (Chroococcus minutus) were exposed
      to four natural organic matter (NOM) isolates. One NOM has been isolated from a
      brown water lake (Schwarzer See) in Brandenburg State; three were obtained from a
      comprehensive Scandinavian NOM research project and originated from Norway
      (Birkenes), Finland (Hietajarvi), and Sweden (Svartberget). METHODS: Cultures of
      D. communis and C. minutus were obtained from the Culture Collection of Algae,
      Gottingen, and maintained in a common medium. The cultures were non-axenic. The
      algae and cyanobacteria were exposed under identical conditions to
      environmentally realistic NOM concentrations. Cell numbers were counted
      microscopically in Neugebauer cuvettes in triplicates. To avoid limitation by
      nutrient depletion, the experiments were terminated after 14 to 15 days. Until
      culture day 12, no growth limitation has been observed in the controls. RESULTS:
      All NOM isolates modulated the growth of the algae and cyanobacteria. During the
      early culture days, there was a slight growth promotion with the coccal green
      alga and to a much lesser degree with the cyanobacterium. Yet, the major effect
      were significant reductions in cell yield in both primary producer cultures. C.
      minutus was much more affected than D. communis. This applies particularly to the
      three tested Scandinavian NOM isolates, which were effective at concentrations
      even below 1 mg L-1 DOC. DISCUSSION: The growth promoting effect may be due to an
      increase in bioavailability of some trace nutrients in the presence of NOM, the
      release of some growth promoting substances by microbial or photochemical
      processing of the NOM, and/or a hormetic effect. The growth reducing effect can
      be explained as a herbicide-like mode of action that affects the photosystem II
      most prevalent by blocking the electron transport chain, absorption of electrons,
      or production of an internal oxidative stress after processing the
      bioconcentrated HS. Furthermore, it may be postulated that also photo-toxicity of
      these HS in the algal cells contributes to the overall toxicity; however,
      experimental evidence is lacking so far. CONCLUSIONS: Upon exposure to HS,
      cyanobacteria appear to be much more sensitive than coccal green algae and
      respond in growth reduction. This high sensitivity of cyanobacteria to HS may
      explain phytoplankton patterns in the field. Eutrophic, humic-rich lakes do not
      support the cyanobacterial blooms characteristic of eutrophic, but humic-poor
      lakes. In the humic-rich systems, raphidophytes or, less frequent, specific
      coccal greens are more common. Obviously, cyanobacteria appear to be unable to
      make advantage of their accessory pigments (phycocyanin) to exploit the reddish
      light prevailing in humic-rich lakes. RECOMMENDATION: . At present, no effective
      structure can be figured out which may be responsible for the adverse effect on
      the cyanobacterial species. It is reserved to future research whether or not HS
      may be applied more specifically (for instance, with elevated moieties of the
      effective structures) as a natural geochemical to combat cyanobacterial blooms.

PMID- 21959536
TI  - Analysis of the Trend and Seasonal Cycle of Carbon Monoxide Concentrations in an
      Urban Area (4 pp).
AB  - BACKGROUND, AIM AND SCOPE: Air quality is an field of major concern in large
      cities. This problem has led administrations to introduce plans and regulations
      to reduce pollutant emissions. The analysis of variations in the concentration of
      pollutants is useful when evaluating the effectiveness of these plans. However,
      such an analysis cannot be undertaken using standard statistical techniques, due
      to the fact that concentrations of atmospheric pollutants often exhibit a lack of
      normality and are autocorrelated. On the other hand, if long-term trends of any
      pollutant's emissions are to be detected, meteorological effects must be removed
      from the time series analysed, due to their strong masking effects. MATERIALS AND
      METHODS: The application of statistical methods to analyse temporal variations is
      illustrated using monthly carbon monoxide (CO) concentrations observed at an
      urban site. The sampling site is located at a street intersection in central
      Valencia (Spain) with a high traffic density. Valencia is the third largest city
      in Spain. It is a typical Mediterranean city in terms of its urban structure and
      climatology. The sampling site started operation in January 1994 and monitored CO
      ground level concentrations until February 2002. Its geographic coordinates are
      W0o22'52? N39o28'05? and its altitude is 11 m. Two nonparametric trend tests are
      applied. One of these is robust against serial correlation with regards to the
      false rejection rate, when observations have a strong persistence or when the
      sample size per month is small. A nonparametric analysis of the homogeneity of
      trends between seasons is also discussed. A multiple linear regression model is
      used with the transformed data, including the effect of meteorological variables.
      The method of generalized least squares is applied to estimate the model
      parameters to take into account the serial dependence of the residuals of this
      model. This study also assesses temporal changes using the Kolmogorov-Zurbenko
      (KZ) filter. The KZ filter has been shown to be an effective way to remove the
      influence of meteorological conditions on O3 and PM to examine underlying trends.
      RESULTS: The nonparametric tests indicate a decreasing, significant trend in the
      sampled site. The application of the linear model yields a significant decrease
      every twelve months of 15.8% for the average monthly CO concentration. The 95%
      confidence interval for the trend ranges from 13.9% to 17.7%. The seasonal cycle
      also provides significant results. There are no differences in trends throughout
      the months. The percentage of CO variance explained by the linear model is 90.3%.
      The KZ filter separates out long, short-term and seasonal variations in the CO
      series. The estimated, significant, long-term trend every year results in 10.3%
      with this method. The 95% confidence interval ranges from 8.8% to 11.9%. This
      approach explains 89.9% of the CO temporal variations. DISCUSSION: The
      differences between the linear model and KZ filter trend estimations are due to
      the fact that the KZ filter performs the analysis on the smoothed data rather
      than the original data. In the KZ filter trend estimation, the effect of
      meteorological conditions has been removed. The CO short-term component is
      attributable to weather and short-term fluctuations in emissions. There is a
      significant seasonal cycle. This component is a result of changes in the traffic,
      the yearly meteorological cycle and the interactions between these two factors.
      There are peaks during the autumn and winter months, which have more traffic
      density in the sampled site. There is a minimum during the month of August,
      reflecting the very low level of vehicle emissions which is a direct consequence
      of the holiday period. CONCLUSIONS: The significant, decreasing trend implies to
      a certain extent that the urban environment in the area is improving. This trend
      results from changes in overall emissions, pollutant transport, climate, policy
      and economics. It is also due to the effect of introducing reformulated gasoline.
      The additives enable vehicles to burn fuel with a higher air/fuel ratio, thereby
      lowering the emission of CO. The KZ filter has been the most effective method to
      separate the CO series components and to obtain an estimate of the long-term
      trend due to changes in emissions, removing the effect of meteorological
      conditions. RECOMMENDATIONS AND PERSPECTIVE: . Air quality managers and policy
      makers must understand the link between climate and pollutants to select optimal
      pollutant reduction strategies and avoid exceeding emission directives. This
      paper analyses eight years of ambient CO data at a site with a high traffic
      density, and provides results that are useful for decision-making. The assessment
      of long-term changes in air pollutants to evaluate reduction strategies has to be
      done while taking into account meteorological variability.

PMID- 21959537
TI  - The OECD Validation Program of the H295R Steroidogenesis Assay for the
      Identification of In Vitro Inhibitors and Inducers of Testosterone and Estradiol
      Production. Phase 2: Inter-Laboratory Pre-Validation Studies (8 pp).
AB  - BACKGROUND: Goals and Scope. In response to concerns that have been raised about
      chemical substances that may alter the function of endocrine systems and result
      in adverse effects on human health, an OECD initiative was undertaken to develop
      and validate in vitro and in vivo assays to identify chemicals that may interfere
      with endocrine systems of vertebrates. Here we report on studies that were
      conducted to develop and standardize a cell-based screening assay using the H295R
      cell line to prioritize chemicals that may act on steroidogenic processes in
      humans and wildlife. These studies are currently ongoing as part of the 'Special
      Activity on the Testing and Assessment of Endocrine Disruptors' within the OECD
      Test Guidelines Program to review, develop, standardize, and validate a number of
      in vitro and in vivo toxicological assays for testing and assessment of chemicals
      concerning their potential to interact with the endocrine system of vertebrates. 
      : Study Design. Six laboratories from five countries participated in the pre
      validation studies. Each laboratory tested the effects of three model chemicals
      on the production of testosterone (T) and estradiol (E2) using the H295R
      Steroidogenesis Assay. Chemicals tested were well described inducers or
      inhibitors of steroidogenic pathways (forskolin, prochloraz and fadrozole). All
      experiments were conducted in 24 well plates following standard protocols. Six
      different doses per compound were analyzed in triplicate per plate. A quality
      control (QC) plate was run in conjunction with the chemical exposure plate to
      account for inter-assay variation. Each chemical exposure was conducted two or
      three times. RESULTS: All laboratories successfully detected increases and/or
      decreases in hormone production by H295R cells after exposure to the different
      model compounds and there was good agreement in the pattern of response for all
      groups. Forskolin increased both T and E2 while fadrozole and prochloraz
      decreased production of both hormones. All chemicals affected hormone production
      in a dose-response manner with the exception of fadrozole which caused maximum
      inhibition of E2 at the two least concentrations tested. Some inter-laboratory
      differences were noted in the alteration of hormone production measured in
      chemically exposed cells. However, with the exception of the production of T
      measured at one laboratory in cells exposed to forskolin, the EC50s calculated
      were comparable (coefficients of variation 34-49%) for all hormones. DISCUSSION:
      and Perspectives. The results indicated that the H295R Steroidogenesis Assay
      protocol was robust, transferable and reproducible across all laboratories.
      However, in several instances that were primarily related to one laboratory there
      were unexplained minor uncertainties related to the inter-laboratory hormone
      production variation. Based on the findings from this Phase 2 pre-validation
      study, the H295R Steroidogenesis Assay protocol is currently being refined. The
      next phase of the OECD validation program will test the refined protocol across
      the same group of laboratories using an extended set of chemicals (~30) that will
      include positive and negative chemical controls as well as a broad spectrum of
      different potential inducers and inhibitors of steroidogenic pathways.

PMID- 21959538
TI  - Biosorption and Biovolatilization of Arsenic by Heat-Resistant Fungi (5 pp).
AB  - GOAL, SCOPE AND BACKGROUND: The aim of this work is to show the ability of
      several fungal species, isolated from arsenic polluted soils, to biosorb and
      volatilize arsenic from a liquid medium under laboratory conditions. Mechanisms
      of biosorption and biovolatilization play an important role in the biogeochemical
      cycle of arsenic in the environment. The quantification of production of volatile
      arsenicals is discussed in this article. METHODS: Heat-resistant filamentous
      fungi Neosartorya fischeri, Talaromyces wortmannii, T. flavus, Eupenicillium
      cinnamopurpureum, originally isolated from sediments highly contaminated with
      arsenic (more than 1403 mg.l-1 of arsenic), and the non-heat-resistant fungus
      Aspergillus niger were cultivated in 40 mL liquid Sabouraud medium (SAB) enriched
      by 0.05, 0.25, 1.0 or 2.5 mg of inorganic arsenic (H3AsO4). After 30-day and 90
      day cultivation under laboratory conditions, the total arsenic content was
      determined in mycelium and SAB medium using the HG AAS analytical method.
      Production of volatile arsenic derivates by the Neosartorya fischeri strain was
      also determined directly by hourly sorption using the sorbent Anasorb CSC (USA).
      RESULTS: Filamentous fungi volatilized 0.025-0.321 mg of arsenic from the
      cultivation system, on average, depending on arsenic concentrations and fungal
      species. The loss of arsenic was calculated indirectly by determining the sum of
      arsenic content in the mycelium and culture medium. The amount of arsenic
      captured on sorption material was 35.7 ng of arsenic (22nd day of cultivation)
      and 56.4 ng of arsenic (29th day of cultivation) after one hour's sorption.
      Biosorption of arsenic by two types of fungal biomass was also discussed, and the
      biosorption capacity for arsenic of pelletized and compact biomass of Neosartorya
      fischeri was on average 0.388 mg and 0.783 mg of arsenic, respectively.
      DISCUSSION: The biosorption and amount of volatilized arsenic for each fungal
      species was evaluated and the effect of initial pH on the biovolatilization of
      arsenic was discussed. CONCLUSIONS: The most effective biovolatilization of
      arsenic was observed in the heat-resistant Neosartorya fischeri strain, while
      biotransformation of arsenic into volatile derivates was approximately two times
      lower for the non-heat-resistant Aspergillus niger strain. Biovolatilization of
      arsenic by Talaromyces wortmannii, T. flavus, Eupenicillium cinnamopurpureum was
      negligible. Results from biosorption experiments indicate that nearly all of an
      uptaken arsenic by Neosartorya fischeri was transformed into volatile derivates.
      RECOMMENDATIONS AND PERSPECTIVE: . Biovolatilization and biosorption have a great
      potential for bioremediation of contaminated localities. However, results showed
      that not all fungal species are effective in the removal of arsenic. Thus, more
      work in this research area is needed.

PMID- 21959539
TI  - Fractionation and Determination of Ah Receptor (AhR) Agonists in Organic Waste
      After Anaerobic Biodegradation and in Batch Experiments with PCB and decaBDE (8
      pp).
AB  - GOALS, SCOPE AND BACKGROUND: Anaerobic digestion of organic household waste can
      lead to an increase in dioxin-like content, as determined by dioxin-specific
      bioassays. This may be a result of bioactivation of Ah receptor (AhR) agonists
      into more potent congeners. Work towards identifying the contributing compound
      groups is important in order to understand the mechanisms and to assess the
      relevance behind this increase in dioxin-like toxicity, since the residue can be
      used as a soil fertilising agent. The aim with the present work was to identify
      compound groups with AhR agonistic properties that caused the previously reported
      increase in dioxin-like activity after anaerobic biodegradation METHODS: Firstly,
      chemical fractionation combined with dioxin bioassay testing was used to find
      bioactive classes of compounds. Secondly, batch digestion experiments with an
      externally added polychlorinated biphenyl (PCB) mixture (Clophen A50) and with
      decabrominated diphenyl ether (decaBDE), respectively, were studied as a possible
      process for transformation of precursors into more potent, dioxin-like compounds.
      Mesophilic (37oC) and thermophilic (55oC) anaerobic digestion were studied. Two
      different dioxin-specific bioassays were used to analyse AhR agonists in the
      biodegraded material, the CELCAD and the DR-CALUX. RESULTS AND DISCUSSION: AhR
      agonist activity was detected in both di- and polyaromatic fractions of digestate
      extracts, which indicated that a diverse mixture of compounds contributed to the
      bioassay responses. No quantifiable activities were induced by the monoaromatic
      fractions. Further fractionation based on planarity revealed higher
      concentrations of AhR agonists than what was detected after the first
      fractionation, probably due to non-additive biological interactions of compounds
      in the extract that were removed in the second fractionation. These results
      showed significant activity in the non-planar diaromatic fractions and in the co
      planar fractions of both diaromates and polyaromates. In the batch experiment
      with externally added PCB, an increase in dioxin-like activity was seen after 21
      days of digestion at mesophilic conditions. After completed digestion, the
      content of AhR agonists was equal to the start concentration. PCB analysis with
      GC-MS indicated that dehalogenation of PCBs occurred in the digestors. The batch
      experiment with decaBDE showed no significant changes in TEQ-concentrations over
      time. CONCLUSIONS: The results show that the previously reported increase of AhR
      agonists during mesophilic anaerobic digestion is probably due to an accumulation
      of several different groups of AhR agonists, both diaromatic and polyaromatic,
      and both co-planar and non-planar. Batch experiments with externally added PCBs
      and decaBDE, respectively, did not result in any accumulation of AhR agonist
      activity after completed digestion, even though chemical analysis indicate a
      dechlorination of PCBs. Complex, unfractionated extracts were difficult to test
      using the bioassay approach. Removal of AhR antagonists or otherwise interacting
      compounds during fractionation may yield bio-TEQ values that are much higher than
      in the original extract. RECOMMENDATIONS AND PERSPECTIVE: . Our results indicate
      that the environmental risk that AhR agonists may pose concerning large-scale
      anaerobic digestion of organic household waste probably depends on the efficiency
      of the digester and the sludge residence time. In order to obtain reliable
      results with the bioassays, an extensive cleanup and fractionation procedure is
      necessary. Without clean up and fractionation, there is a risk for false
      negatives and misleading conclusions. DR-CALUX and CELCAD were both suitable for
      these kinds of studies, provided that suitable fractionation methods are used.

PMID- 21959540
TI  - Fragrances in the Environment: Pleasant odours for nature? (9 pp).
AB  - GOAL, SCOPE AND BACKGROUND: Fragrance preparations or perfumes are used in an
      increasing variety of applications, as for example washing, cleansing, personal
      care products, consumer goods or in applications to modify indoor air. However,
      up to now, little is known to the general or scientific public about their
      chemical identity and the use pattern of single substances, not even for high
      production volume chemicals. Some toxicological data are published for a
      comparatively small number of substances with a focus on sensitisation and dermal
      effects, while other effects are neglected. Information on ecotoxicity and
      environmental fate are rare, especially for long-term exposure. Data for a
      detailed hazard and risk analysis are available in exceptional cases only.
      According to the current legal situation, fragrance industry is self-regulated,
      which means that pre-market risk evaluation is not required for most fragrances.
      Odour and the ability to smell play a major role for wildlife for all taxonomic
      groups. Reproductive and social behaviour, defence, communication and orientation
      depend on volatile compounds which can be identical to those used in fragrance
      preparations. Our interdisciplinary approach leads to the question of whether
      and, if so, to what extent anthropogenic fragrances may influence life and
      reproduction of organisms in the environment. MAIN FEATURES: Information from
      literature on use, exposure and biological effects was combined to analyse the
      state of knowledge. Following an overview of the amounts of fragrances used in
      different consumer products and their release into the environment, the roles of
      odours in nature are shown for a selection of compounds. Existing regulation was
      analysed to describe the data basis for environmental risk evaluation. Finally,
      recommendations for further action are derived from these findings. RESULTS:
      Three main results were elaborated: First, fragrance substances are continuously
      discharged in large amounts into the environment, especially via the waste water.
      Second, there are some indications of negative effects on human health or the
      environment, although the data basis is very thin due to the self regulation of
      the fragrance industry and the regulatory situation of fragrance substances.
      Third, many odoriferous substances used by man are identical to those which are
      signal substances of environmental organisms at very low concentrations, thus
      giving rise to specific mode of actions in the ecosystem. RECOMMENDATION: . For
      the adequate risk assessments of fragrances, test results on their unspecific as
      well as their specific effects as signal substances are needed. This would imply
      prioritisation methods and development of useful test methods for specific
      endpoints for appropriate risk assessments. Before a comprehensive testing and
      evaluation of results has been finished, a minimization of exposure should be
      envisaged. Eco-labelling of products containing acceptable fragrance ingredients
      could be a first step and provide consumers with the respective information.
      Transparency concerning the fragrance ingredients used and their biological
      potency will help to build up confidence between producers and consumers.
      CONCLUSIONS AND PERSPECTIVES: The interdisciplinary approach, bringing together
      chemical, biological, toxicological and ecotoxicological data with information
      provided by manufacturers and with legal and consumer aspects, offers new
      insights into the field of fragrance substances used in consumer products. The
      amounts and application fields of fragrance substances increases while fate and
      effects in the environment are hardly known. The current legal situation is not
      suited to elucidate the effects of fragrances on human health and the environment
      sufficiently, especially as it was shown that fragrances may play a considerable
      role in the ecosystem on the behaviour of organisms. According to the
      precautionary principle, the lack of knowledge should best be tackled by reducing
      exposure, especially for compounds such as fragrance substances where no ethical
      reasons object a substitution by less hazardous chemicals.

PMID- 21959541
TI  - Organic Contaminants from Sewage Sludge Applied to Agricultural Soils. False
      Alarm Regarding Possible Problems for Food Safety? (8 pp).
AB  - GOAL, SCOPE AND BACKGROUND: Sewage sludge produced in wastewater treatment
      contains large amounts of organic matter and nutrients and could, therefore, be
      suitable as fertiliser. However, with the sludge, besides heavy metals and
      pathogenic bacteria, a variety of organic contaminants can be added to
      agricultural fields. Whether the organic contaminants from the sludge can have
      adverse effects on human health and wildlife if these compounds enter the food
      chain or groundwater still remains a point of controversial discussion. MAIN
      FEATURES: This paper presents an overview on the present situation in Europe and
      a summary of some recent results on the possible uptake of organic contaminants
      by crops after addition to agricultural fields by sewage sludge. RESULTS:
      Greenhouse experiments and field trials were performed to study the degradation
      and uptake of organic micro-contaminants in sludge-amended agricultural soil in
      crops, such as barley and carrots grown in agricultural soil amended with
      anaerobically-treated sewage sludge from a wastewater treatment plant, but
      studies hitherto have revealed no immediate risks. Common sludge contaminants
      such as linear alkylbenzene sulphonates (LAS), nonylphenol ethoxylates (NPE),
      polycyclic aromatic hydrocarbons (PAH), bis(diethylhexyl) phthalate (DEHP),
      showed neither accumulation in soil nor uptake in plants. DISCUSSION: It is
      assumed that the annual amount of sewage sludge produced in Europe will increase
      in the future, mainly due to larger amounts of high quality drinking water needed
      by an increasing population and due to increasing demands for cleaner sewage
      water. Application of sewage sludge to agricultural soils is sustainable and
      economical due to nutrient cycling and disposal of sewage sludge. However, this
      solution also involves risks with respect to the occurrence of organic
      contaminants and other potentially harmful contents such as pathogens and heavy
      metals present in the sludge. There have been concerns that organic contaminants
      may accumulate in the soil, be taken up by plants and thereby transferred to
      humans via the food chain. Results obtained so far revealed, however, no
      immediate risk of accumulation of common organic sludge contaminants in soil or
      uptake in plants when applying sewage sludge to agricultural soil. With very high
      dosages of sewage sludge, there may be a risk for accumulation of very apolar
      contaminants, such as DEHP, to the soil. CONCLUSIONS: Any conclusions on the safe
      use of sewage sludge in agriculture have to be drawn carefully, as the studies
      performed until now have been limited. Further studies are required, and before
      final statements can be drawn, it is imminent to study a larger variety of common
      crops and the effect sewage sludge application may have on a possible
      accumulation of organic contaminants in the crops. Furthermore, a larger variety
      of organic contaminants need to be studied and special focus should be given to
      contaminants newly introduced into the environment. Besides investigating
      possible plant uptake of organic contaminants, the fate of these compounds in
      soil after sludge application need to be monitored too. Here, special attention
      has to be given to studies on degradation and the formation of degradation
      products, to weathering and to leaching effects on groundwater, to the
      application of different crops on the same field (crop rotation), to the use of
      full-width tillage and strip tillage, and to long term application of sewage
      sludge on the soil. RECOMMENDATIONS AND PERSPECTIVE: . There are environmental,
      political as well as economical incentives to increase the agricultural
      application of sludge. However, such usage should be performed with care as there
      are also ways in which sludge fertilisation could harm the environment and human
      health. Recently, a new European COST Action (859) has been established covering
      the field of food safety and improved food quality. Part of the Action is dealing
      with the application of sewage sludge in agriculture. Before any political and
      economical measures can be taken, the pros and cons have to be sufficiently
      investigated on a scientific level first.

PMID- 21959542
TI  - Evaluation of Organochlorine Compounds (PCDDs, PCDFs, PCBs and DDTs) in Two
      Raptor Species Inhabiting a Mediterranean Island in Spain (8 pp).
AB  - -: DOI: http://dx.doi.org/10.1065/espr2006.01.015 BACKGROUND: Species that are at
      high levels of the food web have often been used as bioindicators to evaluate the
      presence of persistent contaminants in ecosystems. Most of these species are long
      lived, so pollutant burdens may be integrated in some complex way over time. This
      makes them particularly sensitive to deleterious effects of Persistent Organic
      Pollutants (POPs). Birds have been suggested as useful organisms for monitoring
      pollutant levels. Traditionally such studies have been carried out with raptors
      such as osprey (Pandion haliaetus), peregrine falcon (Falco peregrinus), bald
      eagle (Haliaetus leucocephalus), etc. In this paper we present the results of a
      monitoring study conducted on two raptor species, osprey (Pandion haliaetus) and
      red kite (Milvus milvus), inhabiting a Mediterranean island (Menorca, Spain).
      These two species have different feeding habits; ospreys prey on fish and red
      kites feed on terrestrial species. This study constitutes a good opportunity to
      investigate if differences in feeding habits (aquatic vs. terrestrial) influences
      the contaminants pattern in two species inhabiting the same area. METHODS: The
      study was conducted in a non-destructive way, using only failed eggs, to avoid
      the damage of the population stability. Eggs were collected during the period
      1994-2000. The contaminants examined were dichlorodiphenyltrichloroethanes (DDTs,
      including DDT and its main metabolite, DDE), polychlorinated biphenyls (PCBs),
      including ortho PCBs (PCBs with at least one Chlorine atom in the ortho
      position): #28, 52, 95, 101, 123+149, 118, 114, 153, 132+105, 138, 167, 156, 157,
      180, 170, 189, 194; and non ortho PCBs (PCBs with no Chlorine atom in the ortho
      position): #77, 126, 169 and all the polychlorinated dibenzo-p-dioxins (PCDDs)
      and polychlorinated dibenzofurans (PCDFs) with Chlorine atoms at the 2,3,7 and 8
      position (2,3,7,8-substituted PCDDs and PCDFs). The analysis of organochlorine
      compounds was performed using a sample treatment based on a Solid Phase Matrix
      Dispersion procedure. Ortho PCBs and DDTs were determined by HRGC-uECD; non ortho
      PCBs and PCDD/Fs were determined by HRGC-HRMS. RESULTS AND DISCUSSION: The sum of
      the ortho PCB congeners analysed ranged from 0.94 to 15.03 ug/g wet weight (ww)
      for ospreys and from 1.0 to 11.2 ug/g ww for red kites. In both species, PCB
      congeners #153, #138 and #180 accounted about 75% to total ortho PCB
      concentrations. Regarding non ortho PCBs, for ospreys, concentrations ranged from
      0.16 to 1.39 ng/g wet weight (ww) and for red kites from 0.12 to 0.51 ng/g ww,
      being congener #126 the most abundant. Concerning DDTs, concentration for ospreys
      ranged from 0.07 to 1.03 ug/g ww; and for red kites ranged from 0.90 to 2.10 ug/g
      ww, representing DDE more than 95% of the total DDTs, which proves a past use of
      DDT in the study area. Differences in contaminant levels between species are
      probably associated to feeding habits. The fish-eating species presents the
      highest PCB levels, whereas the terrestrial species exhibits the highest DDT
      levels. PCDD/Fs in ospreys were in the range 2.6-14.2 pg/g ww, while in red kites
      the range was slightly wider (22.2-43.2 pg/g ww), being PCDDs the major
      contributors in black kites. Ospreys had PCDDs similar to PCDF concentrations.
      PCDD/F profiles were mostly influenced by OCDD in both species. Non ortho PCBs
      were the major contributors to calculated Toxic Equivalent Quantity (TEQs) in
      both species. CONCLUSION: In both species studied, ortho-PCBs could represent a
      problem of concern since 57% of the eggs exhibited levels higher than 4 ug/g ww,
      reported as the level that could cause reduced hatchability, embryo mortality,
      and deformities in birds. RECOMMENDATIONS AND OUTLOOK: Results found in this
      study suggest that a more detailed study to clear up possible deleterious effects
      of PCBs on the bird populations studied here should be done.

PMID- 21959543
TI  - An Estimate of Biogenic Emissions of Volatile Organic Compounds during Summertime
      in China (7 pp).
AB  - BACKGROUND: and Aim. An accurate estimation of biogenic emissions of VOC
      (volatile organic compounds) is necessary for better understanding a series of
      current environmental problems such as summertime smog and global climate change.
      However, very limited studies have been reported on such emissions in China. The
      aim of this paper is to present an estimate of biogenic VOC emissions during
      summertime in China, and discuss its uncertainties and potential areas for
      further investigations. MATERIALS AND METHODS: This study was mainly based on
      field data and related research available so far in China and abroad, including
      distributions of land use and vegetations, biomass densities and emission
      potentials. VOC were grouped into isoprene, monoterpenes and other VOC (OVOC).
      Emission potentials of forests were determined for 22 genera or species, and then
      assigned to 33 forest ecosystems. The NCEP/NCAR reanalysis database was used as
      standard environmental conditions. A typical summertime of July 1999 was chosen
      for detailed calculations. RESULTS AND DISCUSSION: The biogenic VOC emissions in
      China in July were estimated to be 2.3*1012gC, with 42% as isoprene, 19% as
      monoterpenes and 39% as OVOC. About 77.3% of the emissions are generated from
      forests and woodlands. The averaged emission intensity was 4.11 mgC m-2 hr-1 for
      forests and 1.12 mgC m-2 hr-1 for all types of vegetations in China during the
      summertime. The uncertainty in the results arose from both the data and the
      assumptions used in the extrapolations. Generally, uncertainty in the field
      measurements is relatively small. A large part of the uncertainty mainly comes
      from the taxonomic method to assign emission potentials to unmeasured species,
      while the ARGR method serves to estimate leaf biomass and the emission algorithms
      to describe light and temperature dependence. CONCLUSIONS: This study describes a
      picture of the biogenic VOC emissions during summertime in China. Due to the
      uneven spatial and temporal distributions, biogenic VOC emissions may play an
      important role in the tropospheric chemistry during summertime. RECOMMENDATIONS
      AND PERSPECTIVE: . Further investigations are needed to reduce uncertainties
      involved in the related factors such as emission potentials, leaf biomass,
      species distribution as well as the mechanisms of the emission activities.
      Besides ground measurements, attention should also be placed on other techniques
      such as remote-sensing and dynamic modeling. These new approaches, combined with
      ground measurements as basic database for calibration and evaluation, can
      hopefully provide more comprehensive information in the research of this field.

PMID- 21959544
TI  - Artificial metalloenzymes for olefin metathesis based on the biotin
      (strept)avidin technology.
AB  - Incorporation of a biotinylated Hoveyda-Grubbs catalyst within (strept)avidin
      affords artificial metalloenzymes for the ring-closing metathesis of N-tosyl
      diallylamine in aqueous solution. Optimization of the performance can be achieved
      either by chemical or genetic means.

PMID- 21959545
TI  - Detecting hidden spatial and spatio-temporal structures in glasses and complex
      physical systems by multiresolution network clustering.
AB  - We elaborate on a general method that we recently introduced for characterizing
      the "natural" structures in complex physical systems via multi-scale network
      analysis. The method is based on "community detection" wherein interacting
      particles are partitioned into an "ideal gas" of optimally decoupled groups of
      particles. Specifically, we construct a set of network representations
      ("replicas") of the physical system based on interatomic potentials and apply a
      multiscale clustering ("multiresolution community detection") analysis using
      information-based correlations among the replicas. Replicas may i) be different
      representations of an identical static system, ii) embody dynamics by considering
      replicas to be time separated snapshots of the system (with a tunable time
      separation), or iii) encode general correlations when different replicas
      correspond to different representations of the entire history of the system as it
      evolves in space-time. Inputs for our method are the inter-particle potentials or
      experimentally measured two (or higher order) particle correlations. We apply our
      method to computer simulations of a binary Kob-Andersen Lennard-Jones system in a
      mixture ratio of A(80)B(20) , a ternary model system with components "A", "B",
      and "C" in ratios of A(88)B(7)C(5) (as in Al(88)Y(7)Fe(5) , and to atomic
      coordinates in a Zr(80)Pt(20) system as gleaned by reverse Monte Carlo analysis
      of experimentally determined structure factors. We identify the dominant
      structures (disjoint or overlapping) and general length scales by analyzing
      extrema of the information theory measures. We speculate on possible links
      between i) physical transitions or crossovers and ii) changes in structures found
      by this method as well as phase transitions associated with the computational
      complexity of the community detection problem. We also briefly consider continuum
      approaches and discuss rigidity and the shear penetration depth in amorphous
      systems; this latter length scale increases as the system becomes progressively
      rigid.

PMID- 21959546
TI  - Yield stresses and flow curves in metallic glass formers and granular systems.
AB  - We discuss the concept of a glass transition line in the temperature-shear-stress
      plane in the context of recent simulation data for a metallic melt and dense
      packed granular systems. Analyzing these data within a schematic model of the
      mode-coupling theory for dense glass formers under shear, values for the critical
      dynamic yield stress (the stress resulting in the limit of arbitrarily slow
      shear, at the glass transition) are estimated. We discuss two possible scenarios,
      that of a continuous rise in the dynamic yield stress at the transition, and that
      of a discontinuous transition, and discuss the data range that needs to be
      covered to decide between the two cases. A connection is made to the two commonly
      drawn versions of the jamming diagram, one convex and one concave regarding to
      the shape of the solid region.

PMID- 21959547
TI  - Learning curve of robotic-assisted microvascular anastomosis in the rat.
AB  - We hypothesized that the learning plateau and learning rate of robotic-assisted
      microvascular anastomosis could be estimated statistically using curve-fitting
      method. Three surgeons with various microsurgical experiences performed 20
      microsurgical anastomoses of the rat femoral artery using the da Vinci robotic
      system (Intuitive Surgical, Inc., Sunnyvale, CA). We evaluated the anastomosis
      time, patency rate, and quality of anastomosis. Objective structured assessment
      of technical skills (OSATS) score which is introduced to assess surgical
      dexterity was also measured. The average starting anastomosis time was 101 +/- 30
      minutes, and the estimated mean learning plateau was 33 +/- 15 minutes. The
      estimated mean learning rate for anastomosis time was 22 +/- 5 trials and the
      estimated mean learning rate for OSATS score was 8 +/- 1 trials. Overall patency
      rate was 90 +/- 5%. Anastomosis patency correlated with OSATS score and quality
      of anastomosis rather than anastomosis time. Important aspects of learning curve
      can be estimated by fitting inverse curves for robotic-assisted microvascular
      anastomosis. As anastomosis time does not necessarily correlate with the patency
      rate, OSATS score might be a valuable tool to evaluate surgeons during training
      for this complicated surgical task.

PMID- 21959548
TI  - Thrombosis of digital arteries associated with tamoxifen use: case report.
AB  - Arterial thrombosis in the upper extremity occurs often at the wrist. We report a
      unique case of thrombosis that involved multiple digital arteries, without radial
      or ulnar artery involvement, which developed only after using tamoxifen despite
      chronic occupational blunt percussive hand use. Revascularization was achieved
      after thrombectomy. Multiple digital arterial thromboses may complicate the use
      of tamoxifen.

PMID- 21959549
TI  - Use of the second dorsal metacarpal artery-based bilobed island flap for thumb
      reconstruction.
AB  - We report the use of the second dorsal metacarpal artery-based bilobed island
      flap harvested from the index and middle fingers for thumb reconstruction. From
      October 2006 to March 2008, the flap was performed in 13 hands in 13 patients (10
      males and 3 females). The mean age at the time of operation was 45 years (range,
      38 to 57 years). The flaps of the index fingers ranged in size from 2.1 * 2.5 cm
      to 4.2 * 3.2 cm. The flaps of the middle fingers were from 2.5 * 2.5 cm to 4.7 *
      3.0 cm. The mean pedicle length was 6.5 cm (range, 5.1 to 8.0 cm). Flap survival
      was achieved in all cases. At final follow-up (mean 43 months; range, 36 to 52
      months), the mean static two-point discrimination of the thumb pulps was 7 mm
      (range, 5 to 10 mm). Our technique is useful and reliable for the thumb
      reconstruction in select cases, with minimal donor-site morbidity.

PMID- 21959550
TI  - Donor-site morbidity of the sensate extended lateral arm flap.
AB  - The free extended lateral arm flap (ELAF) has gained increasing popularity thank
      to its slimness and versatility, longer neurovascular pedicle, and greater flap
      size when compared with the original flap design. The aim of this study was to
      assess the donor-site morbidity associated with this extended procedure. A
      retrospective study of 25 consecutive patients analyzing postoperative
      complications using a visual analogue scale questionnaire revealed high patients
      satisfaction and negligible donor-site morbidity of the ELAF. Scar visibility was
      the commonest negative outcome. Impaired mobility of the elbow had the highest
      correlation with patient dissatisfaction. Sensory deficits or paresthetic
      disorders did not affect patient satisfaction. The extension of the lateral arm
      flap and positioning over the lateral humeral epicondyle is a safe and well
      accepted procedure with minimal donor-site morbidity. To optimize outcomes, a
      maximal flap width of 6 or 7 cm and intensive postoperative mobilization therapy
      is advisable.

PMID- 21959551
TI  - Acellular dermal matrix and negative pressure wound therapy: a tissue-engineered
      alternative to free tissue transfer in the compromised host.
AB  - Free tissue transfer has revolutionized lower extremity reconstruction; however,
      its use in elderly patients with multiple medical problems can be associated with
      elevated rate s of perioperative morbidity and mortality. This study evaluates
      the use of acellular dermal matrix (ADM) in conjunction with negative pressure
      wound therapy (NPWT) and delayed skin graft application as an alternative to free
      tissue transfer in this compromised population. Bilayer, ADM (Integra,
      Plainsboro, NJ) was used in conjunction with NPWT (Wound V.A.C, Kinetic Concepts
      Inc., San Antonio, TX) to achieve vascularized coverage of complex lower
      extremity wounds with denuded tendon and bone in elderly, medically compromised
      patients. Following incorporation, the matrix was covered with split-thickness
      skin graft. Four patients (age range, 50 to 76 years) with multiple medical
      comorbidities were treated with the above protocol. The average time to complete
      vascularization of the matrix was 29 days. Definitive closure with split
      thickness skin graft was achieved in three patients and one wound healed by
      secondary intention. No medical or surgical complications were encountered and
      stable soft tissue coverage was achieved in all patients. This early experience
      suggests that dermal substitute and NPWT with delayed skin graft application can
      provide a reasonable tissue-engineered alternative to free tissue transfer in the
      medically compromised individual.

PMID- 21959552
TI  - Monitored extended secondary arterial ischemia in a free muscle transfer.
AB  - In reconstructive microsurgery, flap failure can be catastrophic to the patient.
      Different monitoring methods have been implemented in an attempt to recognize
      secondary ischemia during its early stages. However, the exact onset of secondary
      ischemia can be difficult to determine because there are no well-documented and
      reliable monitoring techniques that offer true continuous monitoring in a
      clinical setting. Because of the uncertain time in terms of the onset of
      secondary ischemia, the exact length of ischemia before revascularization, the
      secondary ischemia time, cannot be obtained. This is probably part of the reason
      why not much has been published regarding the effect of secondary ischemia time
      in reference to flap survival. We present a case of a free gracilis muscle flap
      that was salvaged despite more than 11 hours of arterial ischemia. The flap was
      monitored using microdialysis and at no time was the ischemia clearly
      demonstrated by clinical inspection. We conclude that clinical monitoring in some
      cases can be an unreliable method for monitoring free muscle transfers suffering
      from arterial ischemia and that further studies are needed for more specific
      guidelines regarding the critical secondary ischemia time in muscle flaps.

PMID- 21959553
TI  - Effect of exercise timing on postprandial lipaemia.

PMID- 21959554
TI  - Cell expansion of human articular chondrocytes on macroporous gelatine scaffolds
      impact of microcarrier selection on cell proliferation.
AB  - This study investigates human chondrocyte expansion on four macroporous gelatine
      microcarriers (CultiSpher) differing with respect to two manufacturing processes
      the amount of emulsifier used during initial preparation and the gelatine cross
      linking medium. Monolayer-expanded articular chondrocytes from three donors were
      seeded onto the microcarriers and cultured in spinner flask systems for a total
      of 15 days. Samples were extracted every other day to monitor cell viability and
      establish cell counts, which were analysed using analysis of variance and
      piecewise linear regression. Chondrocyte densities increased according to a
      linear pattern for all microcarriers, indicating an ongoing, though limited, cell
      proliferation. A strong chondrocyte donor effect was seen during the initial
      expansion phase. The final cell yield differed significantly between the
      microcarriers and our results indicate that manufacturing differences affected
      chondrocyte densities at this point. Remaining cells stained positive for
      chondrogenic markers SOX-9 and S-100 but extracellular matrix formation was
      modest to undetectable. In conclusion, the four gelatine microcarriers supported
      chondrocyte adhesion and proliferation over a two week period. The best yield was
      observed for microcarriers produced with low emulsifier content and cross-linked
      in water and acetone. These results add to the identification of optimal
      biomaterial parameters for specific cellular processes and populations.

PMID- 21959555
TI  - Aminoborylation/Suzuki-Miyaura tandem cross coupling of aryl iodides as efficient
      and selective synthesis of unsymmetrical biaryls.
AB  - Sequential borylation of a first aryl iodide using a dialkylaminoborane followed
      by a Suzuki-Miyaura cross coupling of second aryl iodide ended up with an
      efficient, selective and practical synthesis of unsymmetrical biaryls. This
      tandem coupling shows a wide range of applicability.

PMID- 21959556
TI  - Catheter-based renal denervation for drug-resistant hypertension by using a
      standard electrophysiology catheter.
AB  - AIMS: The endovascular application of low-dose radiofrequency (RF) energy to the
      renal arteries results in effective ablation of sympathetic nerve fibres leading
      to a significant lowering of blood pressure (BP). This study aims to examine the
      feasibility and safety of renal denervation by the use of a standard
      electrophysiology (EP) catheter. METHODS AND RESULTS: Twelve patients (mean age
      62+/-14 years, nine male) with drug resistant hypertension despite medical
      treatment with at least four antihypertensive drugs underwent renal denervation
      by using a standard steerable RF ablation catheter with a 7 Fr diameter
      (Marinr(r); Medtronic Inc., Minneapolis, MN, USA). Low-power RF applications have
      been applied along the length of both renal arteries, consecutively. Assessment
      of 24 hour ambulatory BP was done at baseline, at one, and at three months
      following RF ablation. The mean reduction of 24 hour ambulatory BP was -11/-7
      mmHg at one month and -24/-14 mmHg at three months (p<0.01 for systolic and
      p<0.03 for diastolic blood pressure) with unchanged medication. No vascular
      complications have been observed in the short-term follow-up. The renal function
      as assessed by serum creatinine and proteinuria remained unchanged from baseline.
      CONCLUSIONS: Our preliminary results indicate that the use of a standard RF
      ablation catheter is feasible and safe for sympathetic renal denervation as shown
      by a significant lowering of mean 24 hour ambulatory BP in comparison to baseline
      during short-term follow-up. Whether the use of a standard EP catheter for
      sympathetic renal denervation indeed improves the long-term outcome in resistant
      hypertension, however, remains to be investigated.

PMID- 21959557
TI  - Evaluation of the efficacy and safety of Griflow((r)) Dual, a pre-set two-flow
      infusion device for intravenous immunoglobulin (Flebogamma((r)) 5%)
      administration.
AB  - PURPOSE: A single center, prospective study was performed to assess the efficacy
      and safety of Griflow((r)) Dual a gravity-fed device for intravenous delivery of
      human immunoglobulin Flebogamma((r)). METHODS: A total of 2 infusions in 2 visits
      per patient were assessed using G2 and G3 Griflow((r)) Dual models that provide
      different flow rates adjusted to the patient's weight. To follow the most common
      method of intravenous immunoglobulin administration, infusion through the two-way
      device commenced with the low flow rate capillary (clamp closed) for 30 minutes
      and continued with the high flow rate, opening both ways. Reliability of flow
      delivery (average flow rates), adverse events, as well as functionality in daily
      practice (questionnaire to nurses) were assessed. RESULTS: twenty-five valid
      infusions were evaluated on 13 subjects. Except for the G2 model with closed
      clamp in which 14.5% deviation was observed, actual average flow rate values fell
      well into the maximum 10% deviation permitted with respect to expected charted
      values (G2: 55 and 142 mL/h; G3: 76 and 189 mL/h). Discrepancies could be
      explained by patient's arm movements or posture change during infusion. No
      adverse events related to the study device occurred. In the functionality
      questionnaires, nurse's comfort and safety of infusion with Griflow((r)) Dual
      were rated higher than without Griflow((r)) Dual but lower than with infusion
      pumps. CONCLUSIONS: Although it may not be as precise as an infusion pump,
      Griflow((r)) Dual proved to be a reliable and suitable device to administer
      Flebogamma((r)) 5%. Correct safety should be confirmed in a larger sample.

PMID- 21959558
TI  - New and simple technique for iatrogenic femoral artery pseudoaneurysm treatment:
      Doppler US-guided percutaneous autologous blood injection.

PMID- 21959560
TI  - Effect on anxiety of education programme about care of arteriovenous fistula in
      patients undergoing hemodialysis.
AB  - PURPOSE: This study investigated the impact of education, provided to
      individuals, in whom AV fistula was preferred as a vascular access, regarding
      information and anxiety. METHODS: This experimental study was performed on 32
      patients undergoing hemodialysis between November 2009 and February 2010 in the
      Nephrology Clinic of Sivas Cumhuriyet University Hospital. Patients' data was
      collected by means of Personal Information Form (PIF), AV Fistula Information
      Form (AV-FIF), and Beck Anxiety Inventory (BAI); education brochures were used in
      order to inform the individuals. Collected data were assessed with SPSS .
      Statistical analyses were used in order to assess the data: percentage account,
      paired samples t test. RESULTS: When comparing information and anxiety score of
      individuals prior to and following education about AV fistula care, it was seen
      that information and anxiety scores were low and high respectively, prior to the
      education. Following education, patients' information and anxiety scores became
      higher and lower respectively. All these results were statistically significant
      (P< 0.001). CONCLUSIONS: Education about fistula increased the information level
      about fistula care and decreased anxiety in patients undergoing hemodialysis. It
      is important to perform patient education regularly, because it increases the
      level of orientation towards illness and interventions in patients.

PMID- 21959559
TI  - Balloon angioplasty for disruption of tunneled dialysis catheter fibrin sheath.
AB  - PURPOSE: Management of failing tunneled hemodialysis catheters, sometimes the
      only vascular access for hemodialysis, presents a difficult problem. In spite of
      various techniques having been developed, no consensus has been reached about the
      preferred technique, associated with the longest catheter patency. METHODS: We
      report disruption of the fibrin sheath covering dysfunctional tunneled
      hemodialysis catheter by means of angioplasty, followed by over guidewire
      catheter exchange. RESULTS: Following the procedure, the catheter placed in the
      recovered lumen of the vessel presented correct function. CONCLUSIONS: The
      described procedure allowed maintenance of vascular access in our patient.
      Additionally, dilatation of the concomitant central vein stenosis opens an option
      for another attempt for arteriovenous fistula creation.

PMID- 21959561
TI  - New tunneled haemodialysis catheter placement preserving the vasculature.
AB  - Frequent dialysis line insertion can result in central venous occlusions
      rendering such access of difficult catheterization. New strategies to overcome
      this difficulty have been reported. This problem also occurs together with
      accidental loss of tunneled dialysis catheters, periodically observed in chronic
      hemodialysis patients. We developed a new technique to apply in these situations
      using the old tunnel. It is exposed close to the vein puncture site and opened to
      insert the guidewire, advancing the new catheter along it. A new subcutaneous
      tunnel is performed. We report three cases with successful catheter placement
      using this technique. Catheters functioned appropriately and no complications
      were recorded. We conclude that this maneuver can be used to resolve an extruded
      tunneled hemodialysis catheter while at the same time preserving other vascular
      access routes.

PMID- 21959562
TI  - Inadvertent carotid artery cannulation by dialysis catheter.

PMID- 21959563
TI  - Factor XIIIA transglutaminase expression and secretion by osteoblasts is
      regulated by extracellular matrix collagen and the MAP kinase signaling pathway.
AB  - Osteoblast differentiation is regulated by the presence of collagen type I (COL
      I) extracellular matrix (ECM). We have recently demonstrated that Factor XIIIA
      (FXIIIA) transglutaminase (TG) is required by osteoblasts for COL I secretion and
      extracellular deposition, and thus also for osteoblast differentiation. In this
      study we have further investigated the link between COL I and FXIIIA, and
      demonstrate that COL I matrix increases FXIIIA levels in osteoblast cultures and
      that FXIIIA is found as cellular (cFXIIIA) and extacellular matrix (ecmFXIIIA)
      forms. FXIIIA mRNA, protein expression, cellular localization and secretion were
      enhanced by ascorbic acid (AA) treatment and blocked by dihydroxyproline (DHP)
      which inhibits COL I externalization. FXIIIA mRNA was regulated by the MAP kinase
      pathway. Secretion of ecmFXIIIA, and its enzymatic activity in conditioned
      medium, were also decreased in osteoblasts treated with the lysyl oxidase
      inhibitor beta-aminopropionitrile, which resulted in a loosely packed COL I
      matrix. Osteoblasts secrete a latent, inactive dimeric ecmFXIIIA form which is
      activated upon binding to the matrix. Monodansyl cadaverine labeling of TG
      substrates in the cultures revealed that incorporation of the label occurred at
      sites where fibronectin co-localized with COL I, indicating that ecmFXIIIA
      secretion could function to stabilize newly deposited matrix. Our results suggest
      that FXIIIA is an integral part of the COL I deposition machinery, and also that
      it is part of the ECM-feedback loop, both of which regulate matrix deposition and
      osteoblast differentiation.

PMID- 21959570
TI  - Vulvovaginal candidiasis in postmenopausal women: the role of hormone replacement
      therapy.
AB  - OBJECTIVE: : This study aimed to explore the role of hormone replacement therapy
      (HRT) in susceptibility to vulvovaginal candidiasis (VVC) in a private vulval
      disease referral practice. METHODS: : Between January 2009 and December 2010, 149
      healthy, nondiabetic patients with vulvar conditions were compared for
      significant differences in vaginal swab result, age, and diagnosis between those
      using and not using HRT. Detailed clinical data were collected from those with
      VVC. RESULTS: : The mean ages of the HRT (n = 70) and non-HRT (n = 79) groups
      were 62.5 and 62.5 years, respectively. Positive cultures for Candida were found
      in 34 (48.5%) of 70 patients on HRT and in 2 (3%) of 79 subjects not on HRT (p <
      .001). Culture-positive, clinical VVC was identified in 34 (49%) of 70 patients
      on HRT and in 1 (1%) of 79 patients not on HRT (p < .001). Candida species (32
      Candida albicans and 2 Candida glabrata) were isolated from the 34 VVC patients,
      and of these, 23 (67%) had a history of recurrent or chronic candidiasis before
      menopause. All 34 had been previously treated with antifungal therapy without
      ceasing HRT and had been unresponsive to treatment or had relapse after
      treatment. In 27 (79%) of 34 patients, HRT was suspended during treatment. Of
      those who remained on HRT during treatment or resumed it after treatment,
      prophylactic antifungal treatment was initiated in 15 (44%) to prevent
      recurrence. All patients responded to the antifungal treatment provided HRT was
      suspended or prophylactic treatment was used. CONCLUSIONS: : Postmenopausal women
      taking HRT are significantly more prone to develop VVC than women who are not and
      those with VVC are likely to have been susceptible to it before menopause.

PMID- 21959568
TI  - MRI of double-bundle ACL reconstruction: evaluation of graft findings.
AB  - OBJECTIVE: To demonstrate the magnetic resonance imaging (MRI) findings of double
      bundle (DB) anterior cruciate ligament (ACL) reconstruction grafts. MATERIALS AND
      METHODS: Sixty-six patients with DB ACL reconstruction were evaluated with MRI 2
      years postoperatively. Graft thickness was measured separately by two
      musculoskeletal radiologists. The MRI findings of graft disruption, signal
      intensity (SI) changes, cystic degeneration, arthrofibrosis, and impingement were
      analyzed. The statistical significance of the association between MRI findings
      was calculated. RESULTS: The mean anteromedial (AM) graft thickness was reduced
      9% and the mean posterolateral (PL) graft thickness was reduced 18% from the
      original graft thickness. Disruption was seen in 3% of AM grafts and 6% of PL
      grafts and a partial tear in 8 and 23%, respectively. Both grafts were disrupted
      in 3% of patients. Increased SI was seen in 14% of intact AM grafts and in 60% of
      partially torn AM grafts (p = 0.032). In PL grafts the increased SI was seen in
      51% of the intact grafts and in 93% of the partially torn grafts (p = 0.005).
      Cystic degeneration was seen in 8% of AM grafts and in 5% of PL grafts. Diffuse
      arthrofibrosis was seen in 5% of patients and a localized cyclops lesion in 3% of
      patients. Impingement of the AM graft was seen in 8% of patients. CONCLUSION:
      Both grafts were disrupted in 3% of patients. Also, the frequencies of other
      complications were low. The use of orthogonal sequences in the evaluation of the
      PL graft SI seems to cause volume-averaging artefacts.

PMID- 21959571
TI  - Obstetric outcomes after treatment for cervical intraepithelial neoplasia: six
      years of experience.
AB  - OBJECTIVE: : The purpose of this study was to assess the effect of cervical
      conization on subsequent pregnancy and delivery outcomes. MATERIALS AND METHODS:
      : A retrospective case-control study was performed in patients who underwent
      conization from 2000 to 2005 and had a subsequent delivery. Two case controls
      were matched for each case studied. The obstetric outcomes of the 2 groups were
      compared. A subsequent analysis comparing the 2 excisional techniques used was
      performed. RESULTS: : The study population group included 87 women (29 cases and
      58 controls). Overall, the mean gestation age at delivery (38 vs 39 wk, p =
      .003), prevalence of preterm birth (20.7% vs 5.2%, p = .025), mean birth weight
      (3,035 vs 3279 g, p = .018), and low birth weight (20.7% vs 1.7%, p = .02) were
      statistically different among the cases and controls.In the study group (n = 29),
      large loop excision of the transformation zone was used in 62% (n = 18) and laser
      was used in 38% (n = 11) of the cases. There was no significant difference in the
      medium depth of the excised tissue, the prevalence of preterm birth, low birth
      weight, and the cesarean delivery rate between the 2 techniques. CONCLUSIONS: :
      Despite the small number of cases, this study indicates that excision of the
      transformation zone is associated with an increased risk of overall preterm
      delivery and low-birth weight infants in subsequent pregnancies. No significant
      difference was found between the 2 cervical excision procedures.

PMID- 21959572
TI  - Dermasilk briefs in vulvar lichen sclerosus: an adjuvant tool.
AB  - OBJECTIVE: : The purpose of our study was to evaluate whether briefs made of
      Dermasilk fabric could be an adjuvant tool in the management of vulvar lichen
      sclerosus (LS). MATERIALS AND METHODS: : A controlled, randomized, double-blind
      study versus placebo was conducted, comparing Dermasilk versus standard cotton
      briefs in patients affected by LS during treatment with clobetasol propionate
      0.05% ointment and vitamin E moisturizer. For each patient, an evaluation of
      objective genital signs and subjective symptoms typical of LS was recorded before
      the start of treatment, after 1 month, and after 6 months of the study.
      Statistical analysis was performed with SPSS 17.0 for Windows. RESULTS: : Forty
      two women affected by LS were recruited and divided into those wearing Dermasilk
      or cotton briefs. Patients wearing Dermasilk briefs showed a better improvement
      in the clinical symptoms of burning sensation, skin irritation, and pain (Fisher
      test, p < .0001) compared with the cotton placebo group. The improvement in
      itching was also faster in the Dermasilk group (Fisher exact test, p < .05).
      Erythema also showed a better improvement in the Dermasilk group (Fisher test, p
      < 0.05). CONCLUSIONS: : Dermasilk fabric seems to be a useful adjunct to topical
      treatment in producing a better and more rapid control of symptoms in patients
      with LS.

PMID- 21959573
TI  - Performance of implementing guideline-driven cervical cancer screening measures
      in an inner-city hospital system.
AB  - OBJECTIVE: : In 2006, the American Society for Colposcopy and Cervical Pathology
      updated evidence-based guidelines recommending screening intervals for women with
      abnormal cervical cytology diagnosis. In our low-income inner-city population, we
      sought to improve performance by uniformly applying the guidelines to all
      patients. We report the prospective performance of a comprehensive tracking,
      evidence-based algorithmically driven call back, and appointment scheduling
      system for cervical cancer screening in a resource-limited inner-city population.
      MATERIALS AND METHODS: : Outreach efforts were formalized with algorithm-based
      protocols for triage to colposcopy, with universal adherence to evidence-based
      guidelines. During implementation from August 2006 to July 2008, we prospectively
      tracked performance using the electronic medical record with administrative and
      pathology reports to determine performance variables such as the total number of
      Pap tests, colposcopy visits, and the distribution of abnormal cytology and
      histology results, including all cervical intraepithelial neoplasia 2, 3
      diagnoses. RESULTS: : A total of 86,257 gynecologic visits and 41,527 Pap tests
      were performed system-wide during this period of widespread and uniform
      implementation of standard cervical cancer screening guidelines. The number of
      Pap tests performed per month varied little. The incidence of CIN 1 significantly
      decreased from 117 (68.4%) of 171 during the first tracked month to 52 (54.7%) of
      95 during the last tracked month (p = 0.04). The monthly incidence rate of CIN 2,
      3, including incident cervical cancers, did not change. The total number of
      colposcopy visits declined, resulting in a 50% decrease in costs related to
      colposcopy services and approximately a 12% decrease in costs related to
      excisional biopsies. CONCLUSIONS: : Adherence to cervical cancer screening
      guidelines reduced the number of unnecessary colposcopies without increasing
      numbers of potentially missed CIN 2, 3 lesions, including cervical cancer.
      Uniform implementation of administrative-based performance initiatives for
      cervical cancer screening minimizes differences in provider practices and
      maximizes performance of screening while containing cervical cancer screening
      costs.

PMID- 21959575
TI  - Vaginal blue nevus: report of a case and review of the literature.
AB  - OBJECTIVE: : Blue nevi are extremely rare in the vaginal canal and are suspicious
      for melanoma, especially when multiple lesions are present. We describe a woman
      with multiple blue nevi of the vagina. DESIGN: : We describe 1 case of multiple
      blue nevi of the vagina. RESULTS: : A 37-year-old woman, status after therapy for
      serous carcinoma of the ovary, presented with multiple blue to black macular
      lesions present throughout the vagina. Two of the lesions were examined by biopsy
      and demonstrated dendritic melanocytes. The patient has been closely followed,
      and the lesions remain unchanged. CONCLUSIONS: : Multiple vaginal blue nevi are
      an important differential diagnostic consideration for melanoma of the vagina.
      These lesions, however, are benign and require only clinical follow-up. Excision
      is unnecessary.

PMID- 21959574
TI  - European consensus statement on "HPV Vaccination and Colposcopy".
AB  - We have developed a Europe-wide consensus statement on "HPV Vaccination and
      Colposcopy" under the aegis of the European Federation for Colposcopy. We look at
      the historical perspective, the currently available vaccines, cervical
      vaccination programs, future perspectives, and the impact all this will have on
      cervical cancer screening and colposcopy services.

PMID- 21959576
TI  - An unusual presentation of Wegener disease of the cervix: presenting as cervical
      cancer.
AB  - OBJECTIVE: : Wegener granulomatosis is a rare autoimmune disease of unknown
      cause. It commonly affects the respiratory tracts, lungs, and kidneys.Involvement
      of the uterine cervix is rare, with only 4 previously published cases in the
      literature. MATERIALS AND METHODS: : This is a case report. RESULT: : We describe
      the unusual presentation of Wegener granulomatosis involving the uterine cervix,
      presenting as cervical cancer. CONCLUSIONS: : A review of previously published
      cases of Wegener granulomatosis involving the uterine cervix is presented.We
      report the first case of Wegener granulomatosis involving the cervix without
      antecedent diagnosis or treatment of Wegener granuloma in any other organ.

PMID- 21959577
TI  - Interobserver variability in vaginal fluid wet mount microscopy can be reduced by
      precise definition of flora types and use of phase contrast.

PMID- 21959578
TI  - In reply.

PMID- 21959579
TI  - Computational chemistry of molecular inorganic systems.

PMID- 21959580
TI  - Fermentation strategies for 1,3-propanediol production from glycerol using a
      genetically engineered Klebsiella pneumoniae strain to eliminate by-product
      formation.
AB  - We generated a genetically engineered Klebsiella pneumoniae strain (AK-VOT) to
      eliminate by-product formation during production of 1,3-propanediol (1,3-PD) from
      glycerol. In the present study, the glycerol-metabolizing properties of the
      recombinant strain were examined during fermentation in a 5 L bioreactor. As
      expected, by-product formation was completely absent (except for acetate) when
      the AK-VOT strain fermented glycerol. However, 1,3-PD productivity was severely
      reduced owing to a delay in cell growth attributable to a low rate of glycerol
      consumption. This problem was solved by establishing a two-stage process
      separating cell growth from 1,3-PD production. In addition, nutrient co
      supplementation, especially with starch, significantly increased 1,3-PD
      production from glycerol during fed-batch fermentation by AK-VOT in the absence
      of by-product formation.

PMID- 21959581
TI  - Growth of the oleaginous microalga Aurantiochytrium sp. KRS101 on cellulosic
      biomass and the production of lipids containing high levels of docosahexaenoic
      acid.
AB  - We examined the growth of a novel oleaginous microalga, Aurantiochytrium sp.
      KRS101, using cellulosic materials as nutrients, and the resultant production of
      lipids containing high levels of docosahexaenoic acid (DHA). The microalgal
      strain could grow using either carboxymethylcellulose or cellobiose as a carbon
      source, and produced lipids containing high levels of DHA (49-58% of total fatty
      acids). In line with this growth behavior, carboxymethylcellulase and
      cellobiohydrolase activities were evident in both cell-free lysates and culture
      broths. Additionally, an industrial cellulosic biomass, palm oil empty fruit
      bunches (POEFB), a by-product of the palm oil industry, were utilized by the
      microalgal strain for cell growth and lipid production.

PMID- 21959582
TI  - Intermittent trickling bed filter for the removal of methyl ethyl ketone and
      methyl isobutyl ketone.
AB  - Biodegradations of methyl ethyl ketone and methyl isobutyl ketone were performed
      in intermittent biotrickling filter beds (ITBF) operated at two different
      trickling periods: 12 h/day (ITBF-12) and 30 min/day (ITBF-0.5). Ralstonia sp.
      MG1 was able to degrade both ketones as evidenced by growth kinetic experiments.
      Results show that trickling period is an important parameter to achieve high
      removal performance and to maintain the robustness of Ralstonia sp. MG1. Overall,
      ITBF-12 outperformed ITBF-0.5 regardless of the target compound. ITBF-12 had high
      performance recovery at various inlet gas concentrations. The higher carbon
      dioxide production rates in ITBF-12 suggest higher microbial activity than in
      ITBF-0.5. Additionally, lower concentrations of absorbed volatile organic
      compound (VOC) in trickling solutions of ITBF-12 systems also indicate VOC
      removal through biodegradation. Pressure drop levels in ITBF-12 were relatively
      higher than in ITBF-0.5 systems, which can be attributed to the decrease in
      packed bed porosity as Ralstonia sp. MG1 grew well in ITBF-12. Nonetheless, the
      obtained pressure drop levels did not have any adverse effect on the performance
      of ITBF-12. Biokinetic constants were also obtained which indicated that ITBF-12
      performed better than ITBF-0.5 and other conventional biotrickling filter
      systems.

PMID- 21959583
TI  - Modeling growth, lipid accumulation and lipid turnover in submerged batch
      cultures of Umbelopsis isabellina.
AB  - The production of lipids by oleaginous yeast and fungi becomes more important
      because these lipids can be used for biodiesel production. To understand the
      process of lipid production better, we developed a model for growth, lipid
      production and lipid turnover in submerged batch fermentation. This model
      describes three subsequent phases: exponential growth when both a C-source and an
      N-source are available, carbohydrate and lipid production when the N-source is
      exhausted and turnover of accumulated lipids when the C-source is exhausted. The
      model was validated with submerged batch cultures of the fungus Umbelopsis
      isabellina (formerly known as Mortierella isabellina) with two different initial
      C/N-ratios. Comparison with chemostat cultures with the same strain showed a
      significant difference in lipid production: in batch cultures, the initial
      specific lipid production rate was almost four times higher than in chemostat
      cultures but it decreased exponentially in time, while the maximum specific lipid
      production rate in chemostat cultures was independent of residence time. This
      indicates that different mechanisms for lipid production are active in batch and
      chemostat cultures. The model could also describe data for submerged batch
      cultures from literature well.

PMID- 21959584
TI  - Challenges in studying genomic structural variant formation mechanisms: the short
      read dilemma and beyond.
AB  - Next-generation sequencing (NGS) technologies have revolutionised the analysis of
      genomic structural variants (SVs), providing significant insights into SV de novo
      formation based on analyses of rearrangement breakpoint junctions. The short DNA
      reads generated by NGS, however, have also created novel obstacles by biasing the
      ascertainment of SVs, an aspect that we refer to as the 'short-read dilemma'. For
      example, recent studies have found that SVs are often complex, with SV formation
      generating large numbers of breakpoints in a single event (multi-breakpoint SVs)
      or structurally polymorphic loci having multiple allelic states (multi-allelic
      SVs). This complexity may be obscured in short reads, unless the data is analysed
      and interpreted within its wider genomic context. We discuss how novel approaches
      will help to overcome the short-read dilemma, and how integration of other
      sources of information, including the structure of chromatin, may help in the
      future to deepen the understanding of SV formation processes.

PMID- 21959585
TI  - Opportunities and challenges in developing Alzheimer disease therapeutics.
AB  - Alzheimer disease (AD) is a chronic, progressive disorder with an average disease
      progression of 7-10 years. However, the histopathological hallmark lesions of
      this disease, the extracellular Abeta plaques and the intraneuronal
      neurofibrillary tangles, start as early as childhood in the affected individuals.
      AD is multifactorial and probably involves many different etiopathogenic
      mechanisms. Thus, while AD offers a wide window of opportunity that practically
      includes the whole life span of the affected individuals, and numerous
      therapeutic targets, the multifactorial nature of this disease also makes the
      selection of the therapeutic targets an immensely challenging task. In addition
      to beta-amyloidosis and neurofibrillary degeneration, the AD brain also is
      compromised in its ability to regenerate by enhancing neurogenesis and neuronal
      plasticity. An increasing number of preclinical studies in transgenic mouse
      models of AD show that enhancement of neurogenesis and neuronal plasticity can
      reverse cognitive impairment. Development of both drugs that can inhibit
      neurodegeneration and drugs that can increase the regenerative capacity of the
      brain by enhancing neurogenesis and neuronal plasticity are required to control
      AD.

PMID- 21959587
TI  - Improvement in reflective-emissive dual-mode properties of electrochemical
      displays by electrode modification.
AB  - We studied the electrochromic (EC) and electrochemiluminescent (ECL) properties
      of a novel dual-mode display (DMD) cell that was enabled for reflective and
      emissive modes of representation by introducing both EC and ECL materials into an
      electrochemical cell. We fabricated EC, ECL, and DMD cells based on a simple
      mixture solution or modified electrodes and compared their properties to clarify
      the advantage of a DMD system based on modified electrodes. Both the solution-
      and modified electrode-based DMDs showed EC properties in the reflective mode
      under dc bias application and ECL properties in the emissive mode under ac bias
      application. Although the solution-based DMD cell featured a very simple
      structure, some improvements related to side reaction and quenching reaction were
      required. The modified electrode-based DMD cell was fabricated to improve these
      aspects. The advantage of the DMD model based on the modified electrodes was
      certainly suggested by comparisons of the results with those of EC, ECL, and DMD
      cells based on a simple-mixture solution.

PMID- 21959586
TI  - Simulated brain biopsy for diagnosing neurodegeneration using autopsy-confirmed
      cases.
AB  - Risks associated with brain biopsy limit availability of tissues and the role of
      brain biopsy in diagnosing neurodegeneration is unclear. We developed a simulated
      brain biopsy paradigm to comprehensively evaluate potential accuracy of detecting
      neurodegeneration in biopsies. Postmortem tissue from the frontal, temporal and
      parietal cortices and basal ganglia from 73 cases including Alzheimer's disease
      (AD), Lewy body disease (LBD), frontotemporal lobar degeneration-TDP43 (FTLD
      TDP), multiple system atrophy (MSA), Pick's disease (PiD), corticobasal
      degeneration (CBD) and progressive supranuclear palsy (PSP) were evaluated using
      H&E and immunostains. Brain biopsy was simulated in a blinded manner by masking
      each slide with opaque tape except for an area measuring 10 mm in diameter.
      Diagnoses obtained from frontal cortex only or all 4-brain regions were then
      compared with autopsy diagnoses. Diagnostic sensitivity in frontal cortex was
      highest in FTLD-TDP (88%), AD (80%) and LBD (79%); intermediate for MSA (71%),
      CBD (66%) and PiD (66%) and lowest for PSP (0%) (average 64%). Specificity was
      43%. Sensitivities were enhanced with all 4-brain regions: FTLD-TDP (100%), AD
      (80%), LBD (100%), MSA (100%), CBD (83%), PiD (100%) and PSP (88%) (average 92%).
      Specificity was 71%. Simulated brain biopsy addressed limitations of standard
      brain biopsies such as tissue availability and lack of autopsy confirmation of
      diagnoses. These data could inform efforts to establish criteria for biopsy
      diagnosis of neurodegenerative disorders to guide care of individuals who undergo
      biopsy for enigmatic causes of cognitive impairment or when evidence of an
      underlying neurodegenerative disease may influence future therapy.

PMID- 21959588
TI  - Protamine reversal of low molecular weight heparin:  clinically effective?
AB  - Low molecular weight heparins (LMWHs) are frequently used in the prophylaxis or
      treatment of venous thrombosis, acute coronary syndromes and peri-operative
      bridging. Major bleeding occurs in 1-4% depending on dose and underlying
      condition. Protamine is recommended for reversal but only partially reverses the
      anti-Xa activity and there are very limited data on clinical effectiveness. We
      retrospectively studied the effect of emergency reversal of LMWH with protamine
      in actively bleeding patients and patients requiring emergency surgery in our
      institution. Eighteen patients were identified through haematology
      referral/pharmacy records of protamine prescriptions between 1998 and 2009. Case
      notes were checked for the reversal indication, type/dose of LMWH, dose and
      clinical response to protamine, timing in relation to the last dose of LMWH and
      anti-Xa levels before and after protamine. All but one patient received
      enoxaparin. Fourteen were actively bleeding, three required emergency surgery
      without active bleeding and one had an accidental overdose without bleeding. The
      three patients requiring surgery had an uneventful procedure. In 12 of 14
      patients with active bleeding, protamine could be evaluated. Bleeding stopped in
      eight. In the four with continuing bleeding, one had an additional coagulopathy.
      Protamine only partially affected anti-Xa levels. Protamine may be of use in
      reversing bleeding associated with LMWH but not in all patients. Anti-Xa levels
      were useful to assess the amount of anticoagulation before protamine
      administration but unhelpful in assessing its effect. Better reversal agents and
      methods to monitor LMWH therapy are required.

PMID- 21959589
TI  - Interaction of C1 inhibitor with thrombin on the endothelial surface.
AB  - Thrombin, the central bioregulatory enzyme of haemostasis, also has a potent
      vasopermeability effect on the surface of endothelial cells, and has therefore
      been considered a major link between the activation of the coagulation pathway
      and inflammation. C1 inhibitor inhibits thrombin with a low second-order rate
      constant that can be increased by heparin. The aim of this study was to
      investigate whether the C1 inhibitor-induced inhibition of thrombin is
      potentiated on the endothelial surface. The interaction of C1 inhibitor and
      thrombin was evaluated in an in-vitro system of human umbilical vein endothelial
      cells (HUVECs) to which purified C1 inhibitor and thrombin have been added. The
      role of heparins and selectins has been tested by adding heparinase and Mab to
      selectins. Kinetic analysis under pseudo-first-order conditions showed that the
      inhibitory effect of C1 inhibitor on thrombin is greater on the surface of
      endothelial cells. After incubating nanomolar concentrations of thrombin and
      micromolar concentrations of C1 inhibitor in a purified system, thrombin activity
      remained significant, but was almost totally suppressed in the presence of
      HUVECs. The abolition of such suppression by heparinase and Mab to selectins
      supports the involvement of heparin and selectins in C1 inhibitor-thrombin
      interaction. Furthermore, the second-order rate constant was 25 +/- 3 /s per
      mol/l in our purified system, but increased to 100 +/- 9 /s per mol/l in the
      presence of HUVECs. Our results indicate that C1 inhibitor can inhibit thrombin
      activity on vascular endothelium via binding to selectins and potentiation by
      heparins. This may contribute to the modulation of thrombin activity on
      vasopermeability and on coagulation especially when the major natural
      anticoagulant pathways are impaired.

PMID- 21959590
TI  - Rare deletion from the fibrinogen Bbeta gene in a patient with a provoked venous
      thrombotic event.
AB  - Hypodysfibrinogenemia is characterized by both a qualitative and quantitative
      deficiency of fibrinogen. Here we report a patient with remote history of
      bleeding and presents with provoked deep venous thrombosis associated with
      hypodysfibrinogenemia. Molecular studies identified the presence of fibrinogen
      Epsom, which was previously reported in a family with pregnancy associated
      bleeding. This case illustrates the difficulty in linking the genotype and
      phenotype in patients with defective fibrinogen.

PMID- 21959591
TI  - Effects of long-term anticoagulant therapy on levels of circulating
      microparticles in patients with deep venous thrombosis.

PMID- 21959592
TI  - QRS subtraction for atrial electrograms: flat, linear and spline interpolations.
AB  - The main objective of this article is to implement and compare QRS subtraction
      techniques for intra-cardiac atrial electrograms based on using the surface ECG
      as a reference. A band-pass filter between 8 and 20 Hz followed by rectification,
      and then a low-pass filter at 6 Hz are used for QRS detection. QRS subtraction
      was performed using three different approaches: flat, linear and spline
      interpolations. QRS subtraction affects the power of the signals but it normally
      does not affect the dominant frequency. The average power of the atrial
      electrograms after QRS subtraction is significantly reduced for frequencies above
      10 Hz.

PMID- 21959593
TI  - Trends in rehabilitation robotics.

PMID- 21959594
TI  - Larval feeding stimulants for a rutaceae-feeding swallowtail butterfly, Papilio
      xuthus L. in Citrus unshiu leaves.
AB  - Larvae of a swallowtail butterfly, Papilio xuthus L., feed exclusively on plants
      of the family Rutaceae, including various Citrus crops. Larvae were strongly
      stimulated to feed on paper strips impregnated with ethanolic extracts of host
      plant leaves. Stimulation of feeding on extracts of Citrus unshiu leaves required
      a mixture of chemicals including sugars (D: -glucose, D: -fructose, and D: 
      sucrose), a betaine [(-)-stachydrine], a cyclic peptide (citrusin I), a
      polymethoxyflavone (isosinensetin), and the lipids 1-linolenoylglycerol, 1
      linoleoylglycerol, 1-octadecenoylglycerol, 1-stearoylglycerol, and 1,2
      dilinolenoyl-3-galactosyl-sn-glycerol. When these compounds were assayed
      individually, few larvae consumed test strips. However, larvae readily chewed the
      test strips treated with a mixture of all compounds, indicating that host
      recognition by P. xuthus larvae is mediated by a specific combination of both
      primary and secondary substances. Comparison of 11 stimulant components with 10
      compounds from C. unshiu leaves previously reported as stimulant components for
      oviposition by P. xuthus adult females revealed only one compound, stachydrine,
      as an ingredient in common. While the larval feeding-stimulant mixture is
      dominated by nutrients and other compounds of general significance for primary
      metabolism, the component oviposition stimulants are mostly secondary substances,
      including flavonoid glycosides, protoalkaloids, a cyclitol, and a betaine, that
      have restricted distributions in plants. Reliance by adult females on unique
      profiles of secondary compounds presumably reflects the need to locate and
      recognize specific host-plant species within a diverse flora. Since the initial
      host choice for the larvae is made typically by the ovipositing female, however,
      unique secondary compounds may be less important for larval feeding than are
      compounds useful for indicating food and microhabitat quality once on the host
      plant.

PMID- 21959595
TI  - Single-crystal silicon membranes with high lithium conductivity and application
      in lithium-air batteries.

PMID- 21959596
TI  - Training the next generation of nephrologists.

PMID- 21959597
TI  - Association of pretransplant serum phosphorus with posttransplant outcomes.
AB  - BACKGROUND AND OBJECTIVES: Serum phosphorus levels are associated with mortality,
      cardiovascular disease, and renal function loss in individuals with and without
      chronic kidney disease. The association of pretransplant serum phosphorus levels
      with transplant outcomes is not clear. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Data of the Scientific Registry of Transplant Recipients (SRTR) up
      to June 2007 were linked to the database (2001 through 2006) of one of the U.S.
      based large dialysis organizations (DaVita). The selected 9384 primary kidney
      recipients were divided into five groups according to pretransplant serum
      phosphorus levels (mg/dl): <3.5, 3.5 to <5.5 (reference group), 5.5 to <7.5, 7.5
      to <9.5, and >=9.5. Unadjusted and multivariate adjusted risks for transplant
      outcomes were compared. RESULTS: Patients were 48 +/- 14 years old and included
      37% women and 27% African Americans. After multivariate adjustment, all-cause and
      cardiovascular death hazard ratios were 2.44 (95% confidence interval: 1.28 to
      4.65) and 3.63 (1.13 to 11.64), respectively, in recipients in the >=9.5 group;
      allograft loss hazard ratios were 1.42 (1.04 to 1.95) and 2.36 (1.33 to 4.17) in
      recipients with 7.5 to >9.5 and >=9.5, respectively. No significant association
      with delayed graft function was found. CONCLUSIONS: Pretransplant phosphorus
      levels 7.5 to <9.5 mg/dl and >=9.5 mg/dl were associated with increased risk of
      functional graft failure and increased risk of all-cause and cardiovascular
      deaths, respectively, when compared with 3.5 to <5.5 mg/dl. Additional studies
      are needed to examine whether more aggressive control of pretransplant serum
      phosphorus may improve posttransplant outcomes.

PMID- 21959598
TI  - Effectiveness and safety of warfarin initiation in older hemodialysis patients
      with incident atrial fibrillation.
AB  - BACKGROUND AND OBJECTIVES: Although generally recommended in atrial fibrillation
      (AF) patients, the effectiveness and safety of oral anticoagulation in dialysis
      patients with AF is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We
      assembled a cohort of older hemodialysis patients who initiated dialysis without
      prior record of AF and who had prescription drug benefits through three state
      administered programs. The index event was a first hospitalization with diagnosed
      AF; patients with any recorded prior warfarin use were excluded. Eligible
      patients survived >=30 days from discharge, and new warfarin use was recorded
      from prescription records during that 30-day window. Propensity-matched warfarin
      users and nonusers were compared using Cox regression. Outcomes included ischemic
      stroke, hemorrhagic stroke, and mortality. RESULTS: Among 2313 patients with new
      AF who survived 30 days from discharge, 249 (10.8%) filled a prescription for
      warfarin. Comparing 237 warfarin users and 948 propensity-matched nonusers over
      2287 person-years of follow-up, the occurrence of ischemic stroke was similar (HR
      = 0.92; 95% CI, 0.61 to 1.37), whereas warfarin users experienced twice the risk
      of hemorrhagic stroke (HR = 2.38; 95% CI, 1.15 to 4.96). The risks of stroke,
      gastrointestinal hemorrhage, and mortality did not differ between groups. As
      treated analyses yielded similar findings, as did analyses restricted to patients
      with CHADS(2) scores >=2. CONCLUSIONS: Although we confirmed association between
      warfarin use and hemorrhagic stroke in dialysis patients with AF, we found no
      association between warfarin use and ischemic stroke. Adequately powered
      randomized trials are required to conclusively determine the risks and benefits
      of the studied warfarin indication in hemodialysis patients.

PMID- 21959599
TI  - Early outcomes among those initiating chronic dialysis in the United States.
AB  - BACKGROUND AND OBJECTIVES: Approximately one million Americans initiated chronic
      dialysis over the past decade; the first-year mortality rate reported by the U.S.
      Renal Data System was 19.6% in 2007. This estimate has historically excluded the
      first 90 days of chronic dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:
      To characterize the mortality and hospitalization risks for patients starting
      chronic renal replacement therapy, we followed all patients initiating dialysis
      in 1733 facilities throughout the United States (n = 303,289). Mortality and
      hospitalizations within the first 90 days were compared with outcomes after this
      period, and the results were analyzed. Standard time-series analyses were used to
      depict the weekly risk estimates for each outcome. RESULTS: Between 1997 and
      2009, >300,000 patients initiated chronic dialysis and were followed for >35
      million dialysis treatments; the highest risk for morbidity and mortality
      occurred in the first 2 weeks of treatment. The initial 2-week risk of death for
      a typical dialysis patient was 2.72-fold higher, and the risk of hospitalization
      was 1.95-fold higher when compared to a patient who survived the first year of
      chronic dialysis (week 53 after initiation). Similarly, over the first 90 days,
      the risk of mortality and hospitalization remained elevated. Thereafter, between
      days 91 and 365, these risks decreased considerably by more than half. Surviving
      these first weeks of dialysis was most associated with the type of vascular
      access. Initiating dialysis with a fistula was associated with a decreased early
      death risk by 61%, whereas peritoneal dialysis decreased the risk by 87%.
      CONCLUSIONS: The first 2 weeks of chronic dialysis are associated with heightened
      mortality and hospitalization risks, which remain elevated over the ensuing 90
      days.

PMID- 21959600
TI  - Access survival amongst hemodialysis patients referred for preventive angiography
      and percutaneous transluminal angioplasty.
AB  - BACKGROUND AND OBJECTIVES: Referring hemodialysis patients for elective access
      angiography and percutaneous transluminal angioplasty (PTA) is commonly done to
      prevent access failure, yet the effectiveness of this procedure remains unclear.
      DESIGN, SETTING, PARTICIPANTS, & MEASURES: An observational matched cohort
      analysis among 40,132 Medicare beneficiaries receiving hemodialysis with a
      fistula or graft was performed. Cox regression was used to determine whether
      access intervention was associated with improved 1-year access survival. RESULTS:
      Nonsurgical access intervention was found to be frequent at a rate of 20.9
      procedures per 100 access years. In the 1-year period after intervention using
      angiography and PTA, the overall access failure rate was 53.7 per 100 access
      years in the intervention group and 49.6 in the nonintervention group (HR = 1.02;
      95% CI, 0.96 to 1.08). Similar findings were also seen when the analysis was
      repeated in only fistulas (HR = 1.06; 95% CI, 0.98 to 1.15) and grafts (HR =
      0.95; 95% CI, 0.86 to 1.05). In patients with a low intra-access flow rate (HR =
      0.86; 95% CI, 0.75 to 0.99) or a new access (HR = 0.79; 95% CI, 0.71 to 0.89),
      angiography and PTA significantly increased access survival when compared with
      nonintervention (P for interaction was <0.0001). Angiography-PTA-related upper
      extremity hematoma, vessel injury, or embolism-thrombosis occurred in 1.1% of all
      patients. CONCLUSIONS: Access characteristics significantly modify the survival
      benefits of angiography and PTA intervention where the benefits of these
      interventions are most seen in newer accesses or accesses with insufficient flow.

PMID- 21959601
TI  - Hepatic effects of lung-protective pressure-controlled ventilation and a
      combination of high-frequency oscillatory ventilation and extracorporeal lung
      assist in experimental lung injury.
AB  - BACKGROUND: Ventilation with high positive end-expiratory pressure (PEEP) can
      lead to hepatic dysfunction. The aim of this study was to investigate the hepatic
      effects of strategies using high airway pressures either in pressure-controlled
      ventilation (PCV) or in high-frequency oscillatory ventilation (HFOV) combined
      with an arteriovenous extracorporeal lung assist (ECLA). MATERIAL/METHODS:
      Pietrain pigs underwent induction of lung injury by saline lavage. Ventilation
      was continued for 24 hours either as PCV with tidal volumes of 6 ml/kg and PEEP 3
      cmH2O above the lower inflection point of the pressure-volume curve or as HFOV
      (>= 12 Hz) with a mean tracheal airway pressure 3 cmH2O above the lower
      inflection point combined with arteriovenous ECLA (HFOV+ECLA). Fluids and
      norepinephrine stabilized the circulation. The indocyanine green plasma
      disappearance rate, serum bilirubin, aspartate aminotransferase, alanine
      aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, glutamate
      dehydrogenase, lactate dehydrogenase and creatine kinase were determined
      repeatedly. Finally, liver neutrophils were counted and liver cell apoptosis was
      assessed by terminal deoxynucleotidyl transferase nick end labeling (TUNEL).
      RESULTS: Aspartate aminotransferase increased in the PCV group about three-fold
      and in the HFOV+ECLA group five-fold (p<0.001). Correspondingly, creatine kinase
      increased about two-fold and four-fold, respectively (p<0.001). Lactate
      dehydrogenase was increased in the HFOV+ECLA group (p<0.028). The number of
      neutrophils infiltrating the liver tissue and the apoptotic index were low.
      CONCLUSIONS: High airway pressure PCV and HFOV with ECLA in the treatment of
      lavage-induced lung injury in pigs did not cause liver dysfunction or damage. The
      detected elevation of enzymes might be of extrahepatic origin.

PMID- 21959602
TI  - Rosiglitazone protects against severe hemorrhagic shock-induced organ damage in
      rats.
AB  - BACKGROUND: Hemorrhagic shock (HS) followed by resuscitation can induce the
      production of several inflammatory mediators and lead to multiple organ
      dysfunction. The molecular mechanism of biologic responses to rosiglitazone has
      an anti-inflammatory effect. The present study was designed to investigate the
      effects of rosiglitazone on physiopathology and inflammatory mediators after HS
      in rats. MATERIAL/METHODS: HS was induced in rats by withdrawing 60% of the total
      blood volume from a femoral artery catheter, immediately followed by intravenous
      injection of 0.3 mg/kg rosiglitazone. Mean arterial pressure (MAP) and heart rate
      (HR) were monitored continuously for 12 h. Levels of biochemical parameters,
      including GOT, GPT, BUN, Cre, LDH, CPK, and lactate were measured at 30 min
      before induction of HS and 0, 1, 3, 6, 9, and 12 h after HS, while an equal
      volume of normal saline was replaced as fluid resuscitation. Inflammatory
      mediators, including tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL
      6) and monocyte chemoattractant protein-1 (MCP-1), were measured in serum at 1
      and 12 h after HS. The kidneys, liver, lungs, and small intestine were removed
      for histological assessment by hematoxylin and eosin stained at 48 h after HS.
      RESULTS: HS significantly increased blood GOT, GPT, BUN, Cre, LDH, CPK, lactate,
      glucose, TNF-alpha, IL-6 and MCP-1 levels, induced tachycardia, and decreased
      mean arterial pressure (MAP) in rats. Treatment with rosiglitazone improved
      survival rate, decreased the markers of organ injury, and suppressed the release
      of TNF-alpha, IL-6, and MCP-1 after HS in rats. CONCLUSIONS: Treatment with
      rosiglitazone suppresses the release of serum TNF-alpha, IL-6 and MCP-1, and
      ameliorates HS-induced organ damage in rats.

PMID- 21959603
TI  - Radiation dose effect of DNA repair-related gene expression in mouse white blood
      cells.
AB  - BACKGROUND: The aim of this study was to screen molecular biomarkers for
      biodosimetry from DNA repair-related gene expression profiles. MATERIAL/METHODS:
      Mice were subjected to whole-body exposure with 60Co gamma rays with a dose range
      of 0-8 Gy at a dose rate of 0.80 Gy/min. RNA was extracted from the peripheral
      blood of irradiated mice at 4, 8, 12, 24 and 48hrs post-irradiation. The mRNA
      transcriptional changes of 11 genes related to DNA damage and repair were
      detected using real-time quantitative polymerase chain reaction (RT-PCR).
      RESULTS: Of the 11 genes examined, CDKN1A (cyclin-dependent kinase inhibitor 1A
      or p21, Cip1) and ATM (ataxia telangiectasia mutated) expression levels were
      found to be heavily up- and down-regulated, respectively, with exposure dose
      increasing at different post-irradiation times. RAD50 (RAD50 homolog), PLK3 (polo
      like kinase 3), GADD45A (growth arrest and DNA damage-inducible, alpha), DDB2
      (damage-specific DNA-binding protein 2), BBC3 (BCL2-binding component 3) and IER5
      (immediate early response 5) gene expression levels were found to undergo
      significant oscillating changes over a broad dose range of 2-8 Gy at post
      exposure time points observed. Three of the genes were found not to change within
      the observed exposure dose and post-radiation time ranges. CONCLUSIONS: The
      results of this study add to the biodosimetry with biomarker data pool and will
      be helpful for constructing appropriate gene expression biomarker systems to
      evaluate radiation exposure doses.

PMID- 21959604
TI  - A severe complication after ST-segment elevation myocardial infarction (Part 2).
AB  - We report the case of a 70-year-old woman with ST-segment elevation myocardial
      infarction of the anterior wall, complicated by ventricular septal rupture (two
      septal defects--VSDs) with symptoms of cardiogenic shock. After 6 weeks of
      conservative treatment with inotropes and intra-aortic balloon support, the
      patient underwent surgical repair of VSDs with good clinical outcome.

PMID- 21959605
TI  - Predictors of cardiac hepatopathy in patients with right heart failure.
AB  - BACKGROUND: Some patients with right heart failure develop cardiac hepatopathy
      (CH). The pathophysiology of CH is thought to be secondary to hepatic venous
      congestion and arterial ischemia. We sought to define the clinical and
      hemodynamic characteristics associated with CH. MATERIAL/METHODS: A retrospective
      cross sectional analysis was performed in which subjects were identified from our
      institutional cardiology database if echocardiography showed either right
      ventricular (RV) hypokinesis or dilatation, and was performed within 30 days of
      right heart catheterization. A chart review was then performed to identify
      patient clinical characteristics and to determine if the patients had underlying
      liver disease. Subjects with non-cardiac causes for hepatopathy were excluded.
      RESULTS: In 188 included subjects, etiology for right heart dysfunction included
      left heart failure (LHF), shunt, pulmonary hypertension, mitral- tricuspid- and
      pulmonic valvular disease. On multivariate analysis, higher RV diastolic pressure
      and etiology for RV dysfunction other than LHF were both associated with CH. Low
      cardiac output was associated with CH only amongst those without LHF.
      CONCLUSIONS: CH is most often seen in subjects with elevated RV diastolic
      pressure suggesting a congestive cause in most cases. CH associated with low
      cardiac output in patients without LHF suggests that low flow may be contributing
      to the patophysiology in some cases.

PMID- 21959606
TI  - Involvement of the lymphatic system in salt-sensitive hypertension in humans.
AB  - BACKGROUND: The mechanisms of salt sensitivity as an important intermediate
      phenotype of essential hypertension remain elusive. A novel theory proposes that
      lymphatic vessels regulate sodium and fluid homeostasis. Since vascular
      endothelial growth factor C (VEGF-C) plays a vital role in lymphatic capillary
      hyperplasia, we hypothesized that VEGF-C was involved in salt-sensitive
      hypertension. We therefore investigated its plasma concentration in salt
      sensitive subjects. MATERIAL/METHODS: Twenty-seven subjects (BP <= 160/100 mmHg;
      age range 25-50 years) from a rural community of northern China were enrolled in
      this study. The baseline BP of volunteers was monitored for 3 days, followed by a
      low-salt diet for 7 days (3 g/day, NaCl) and a high-salt diet for 7 days (18
      g/day, NaCl). Those who exhibited a BP increase of 10% from low-salt period to
      high-salt period were diagnosed as salt-sensitive subjects. The concentration of
      plasma VEGF-C was measured by an immunoenzyme method (ELISA). RESULT: High salt
      intake significantly increased the plasma VEGF-C level. It was higher in the salt
      sensitive subjects (3642.2 +/- 406.1 pg/ml) than in the salt-resistant subjects
      (2249.8 +/- 214.6 pg/ml). The comparison of VEGF-C levels between the 2 groups
      had significant statistical difference (P<0.01). CONCLUSIONS: The VEGF-C level
      increases significantly in the salt-sensitive subjects after high salt intake.
      VEGF-C could be used as a biomarker of salt sensitivity.

PMID- 21959607
TI  - IGF-I and IGFBP-3 before and after inpatient alcohol detoxification in alcohol
      dependent subjects.
AB  - BACKGROUND: It is unclear whether alcohol detoxification has an effect on factors
      that are involved in growth, metabolic functions and cell proliferation. Alcohol
      abuse is associated with low IGF-I levels that tend to rise after alcohol
      withdrawal. There is a paucity of studies on the course of IGFBP-3 (the main
      binding protein for IGF-I) after alcohol detoxification. MATERIAL/METHODS: We
      prospectively assessed IGF-I and IGFBP-3 changes at the time of admission and
      after 4 to 6 weeks of detoxification in an inpatient alcohol detoxification
      facility in 118 alcohol-dependent subjects given a regular hospital diet. No
      participants dropped out of the study. RESULTS: Changes in IGF-I after alcohol
      detoxification showed a marked dimorphism in altered hepatic biochemistry upon
      admission, with a rise in those with normal liver enzymes upon admission (p =
      0.016, Kruskall-Wallis) and a drop in those with elevated liver enzymes upon
      admission (p = 0.05); the latter was noted in subjects that had consumed alcohol
      close to the time of admission. Overall, however, IGF-I and IGFBP-3 were within
      normal limits for most subjects both upon admission and after alcohol
      detoxification; no significant differences were detected among the examined
      parameters in men vs. women, and there were no significant correlations of IGF-I,
      IGFBP-3 or the IGF-I/IGFBP-3 molar ratio with BMI or age. CONCLUSIONS: Regardless
      of hepatic enzymes' elevation, alcohol detoxification had overall slight effects
      on IGF-I and IGFBP-3.

PMID- 21959608
TI  - Low frequency of HFE gene mutations in Croatian patients suspected of having
      hereditary hemochromatosis.
AB  - BACKGROUND: Hereditary hemochromatosis (HH) is a common autosomal recessive
      disorder in populations of European descent. It is characterized by a variable
      prevalence of mutations in the hemochromatosis gene (HFE) in different countries
      and a complex relationship between the HFE genotype and the HH phenotype. Genetic
      analysis has not been conducted in Croatian patients with iron overload. The aim
      of this study was to determine whether HFE mutations, C282Y, H63D, and S65C were
      correlated with clinical and biochemical parameters in Croatian patients with
      suspected HH. MATERIAL/METHODS: Clinical examination, biochemical analysis, and
      genotyping were performed in 175 patients suspected of having HH. The control
      group consisted of 350 healthy blood donors. RESULTS: Among the patients, 20% had
      genotypes related to HH--7.4% were homozygous for C282Y, 6.3% were compound
      heterozygous for C282Y and H63D, 5.7% were homozygous for H63D, and 0.6% was
      compound heterozygous for C282Y and S65C. The allelic frequencies were 14.6% for
      C282Y mutation, 23.7% for H63D mutation, and 1.4% for S65C mutation. A comparison
      of the clinical and laboratory profiles of patients revealed that C282Y
      homozygotes had higher frequencies of all clinical symptoms and higher levels of
      biochemical parameters than others. The C282Y/H63D compound heterozygotes and
      H63D homozygotes were found to be clinically important, despite the fact that
      they were associated with less severe disease. CONCLUSIONS: Our results show that
      HFE mutations are responsible for only about 20% of Croatian patients with
      suspected HH. Screening with biochemical methods and HFE genotyping may be not
      sufficient for diagnoses in the Croatian population.

PMID- 21959609
TI  - Contralateral suppression of otoacoustic emissions: input-output functions in
      neonates.
AB  - BACKGROUND: The literature suggests that contralateral acoustic stimulation (CAS)
      alters the amplitude of the distortion product otoacoustic emissions (DPOAEs),
      but it is still unknown whether the DPOAE Input/Output (I/O) functions are also
      affected. To elucidate this aspect of the DPOAEs, the present study assessed the
      effects of CAS on DPOAE I/O functions at the frequencies of 2 kHz and 4 kHz, in a
      sample of term neonatal subjects. MATERIAL/METHODS: Sixty randomly selected
      neonates were included in the study. The DPOAE I/O functions were obtained at 2
      kHz and 4 kHz, in the presence of a 60 dB SPL broad band-contralateral white
      noise, using the TDH39 headphones contralaterally. DPOAEs were recorded up to a
      stimulus level of L2 = 35 dB peSPL. RESULTS: Significant DPOAE amplitude
      suppression effects were observed at various L2 stimulus levels for both tested
      frequencies at 2 and 4 kHz. In contrast, the corresponding DPOAE slopes showed
      various alterations that were not statistically significant. CONCLUSIONS: The
      data from the present study show that contralateral acoustic stimulation
      significantly affects only the amplitude of the DPOAE I/O functions; the slope is
      affected, but not significantly. This observation can shed light on the nature of
      CAS, suggesting that the latter is primarily a linear phenomenon without the
      cochlear compression and non-linear components seen in the healthy cochlea. From
      the available data it is not possible to infer whether the sample size has
      influenced the obtained results and the study should be repeated with a larger
      sample size and assessing more frequencies.

PMID- 21959610
TI  - Bone metabolism assessment, bone metabolism index designation and the
      determination of its normal values range in young healthy women.
AB  - BACKGROUND: Bone metabolism assessment requires the determination of bone mass
      and quality. The bone metabolism was assessed with the modified bone scintigraphy
      using 99mTc-MDP. The elaboration of radioisotopic method and program allowed for
      the assessment of bone metabolism, index of bone metabolism assay and definition
      of its normal values range with the possibility of clinical application.
      MATERIAL/METHODS: We examined 70 healthy young women with normal BMI, in which
      bone system was assessed with scintigraphic and densitometric examinations, and
      bone turnover markers definition together with hormonal and biochemical blood
      tests were performed. Group exclusion examinations were also performed, including
      basic, biochemical and hormonal blood tests, bone turnover markers and
      densitometric examinations with DXA technique. The scintigraphic examinations
      were performed using a gamma camera after 99mTc-MDP injection. After the
      application of the BONS method and program, the normal values range was
      determined with the STATISTICA 8 program. RESULTS: The normal results of basic,
      biochemical, hormonal and vascular tests were obtained. The examinations of bone
      turnover markers confirmed the balance between bone formation and bone resorption
      processes. The normal results of densitometric examinations excluded osteopeny or
      osteoporosis. The normal values range of IBM in young healthy women was between
      84.08 and 105. CONCLUSIONS: The elaborated BONS program and method allow for the
      quantitative assessment of bone quality and definition of IBM normal values
      range. The quantitative scintigraphic bone examinations provide an alternative to
      the bone markers examination for obtaining information about bone metabolism.

PMID- 21959611
TI  - The effect of polyvinylpyrrolidone-sodium hyaluronate gel (Gelclair) on oral
      microbial colonization and pain control compared with other rinsing solutions in
      patients with oral mucositis after allogeneic stem cells transplantation.
AB  - BACKGROUND: Gelclair is an oral lubricating gel used in the management of oral
      mucositis (OM). We evaluated its efficacy, tolerance and impact on oral cavity
      microbial colonization in patients with OM after allogeneic hematopoietic stem
      cells transplantation. MATERIAL/METHOD: Gelclair was administered in a group of
      22 patients with active OM. A control group of 15 patients used other rinsing
      solutions (chlorhexidine, benzydamine, salvia). Tests with oral cavity swabs for
      microbiology analysis were performed once a week. RESULTS: The characteristics of
      OM in both groups were comparable, and rinsing solutions had satisfactory
      tolerability. There was no difference in the median improvement of oral intake
      and OM-related pain relief, which was assessed mostly as "slight effect". In the
      Gelclair group, the effect duration was longer (median 3 [0-5] vs. 1 [0-3] hours,
      p = 0.001). There was significant increase of Enterococcus faecalis and Candida
      sp. colonization of the oral cavity over the course of the hospitalization and
      significantly reduced incidence of such colonization in patients with OM in the
      Gelclair group: 1/22 (5%) vs. 6/15 (40%), p = 0.01. In vitro tests showed
      inhibited growth of Enterococcus faecalis and Candida sp. colonies within the
      area of the Gelclair application. CONCLUSIONS: Gelclair may be individually
      helpful in the management of OM and pain in patients after allogeneic stem cells
      transplantation. Its use did not lead to worsened oral bacterial and yeast
      colonization and probably even helped to protect mucosa from Enterococcus and
      Candida sp. Further studies based on larger cohorts are needed.

PMID- 21959613
TI  - Assessment of quality of life in patients with chronic pancreatitis.
AB  - BACKGROUND: Quality of life (QOL) has increasingly become a factor in management
      decisions in patients with chronic diseases. Chronic pancreatitis (CP) is a
      debilitating disorder that causes not only pain and endo/exocrine insufficiency
      but is also connected with some social issues. The aim of this study was to
      assess QOL in patients with chronic pancreatitis in correlation with the disease
      activity or the environmental/social factors that can influence their well-being.
      MATERIAL/METHODS: The study group comprised 43 patients with CP: M/F 37/6; mean
      age 47.9 +/- 8.6; range: 30-74 yrs. The control group consisted of 40 healthy
      volunteers of comparable demographics. Different degrees of CP activity were
      defined using the Cambridge classification. Pain intensity and frequency were
      assessed using a pain index. QOL was assessed using the Short-Form-36
      questionnaire. RESULTS: Mean QOL scores in CP were lower compared to the control
      group in all SF-36 domains, particularly in general health perception, physical
      functioning, role-physical (p<0.001) and vitality (p<0.05). We observed
      correlation of QOL results and pain index in all domains, and number of the
      disease relapses and body weight in 5 out of 8 domains (p<0.001 and p<0.05,
      respectively). The worst QOL scores were obtained in retired patients, as well as
      in unemployed persons in almost all SF-36 domains (p<0.001). CONCLUSIONS: Chronic
      pancreatitis significantly impairs patients' quality of life. Severity of
      abdominal pain, low body weight, and loss of work were the factors most closely
      associated with poor health status perception.

PMID- 21959612
TI  - The impact of capsulorhexis diameter, localization and shape on posterior capsule
      opacification.
AB  - BACKGROUND: The aim of this study was to evaluate the impact of capsulorhexis
      diameter, localization and shape on posterior capsule opacification (PCO)
      development after cataract extraction with phacoemulsification. MATERIAL/METHODS:
      We retrospectively analyzed of 297 patients who underwent phacoemulsification and
      AcrySof SA60AT implantation. In a first group of 97 patients, 53 received small
      capsulorhexis (3.9 to 4.9 mm in diameter) and 44 patients received large
      capsulorhexis (5.0 to 5.9 mm in diameter). Another group of 99 patients was split
      into subgroups--66 patients whose capsulorhexis were centrally located and 33
      patients whose capsulorhexis were paracentral. A third group of 101 patients was
      split into subgroups--a subgroup of 59 patients were classified as having a
      regularly rimmed capsulorhexis and a subgroup of 42 patients as having an
      irregularly rimmed capsulorhexis. At 6 months follow-up, PCO was classified as
      none, mild, moderate, or severe, depending on the number of quadrants involved.
      RESULTS: 86.79% of the patients with a small capsulorhexis had no or mild PCO
      (p<0.001), whereas, 68.18% of the patients with a large capsulorhexis experienced
      moderate or severe PCO; 89.4% of the patients with a central capsulorhexis had no
      or mild PCO (p<0.001), whereas, 75.75% of the patients with a paracentral
      capsulorhexis had moderate or severe PCO; 86.44% of the patients with a regularly
      rimmed anterior capsulorhexis had no or mild PCO (p<0.001); and 69.04% of the
      patients with an irregular capsulorhexis rim had moderate or severe PCO.
      CONCLUSIONS: A small capsulorhexis diameter, its central localization and regular
      shape result in less PCO following phacoemulsification.

PMID- 21959614
TI  - A randomized, double-blind, placebo-controlled trial of preemptive analgesia with
      bupivacaine in patients undergoing mastectomy for carcinoma of the breast.
AB  - BACKGROUND: In this prospective, randomized, placebo-controlled, double-blinded
      clinical trial we tested the hypothesis that preemptive analgesia with
      bupivacaine applied in the area of the surgical incision in patients undergoing
      mastectomy for breast cancer would reduce post-operative acute pain and would
      reduce the amount of analgesics used during surgery and in the post-operative
      period. MATERIAL/METHODS: Participants were assigned into 1 of 2 groups--with
      bupivacaine applied in the area of surgical incision or with placebo. We assessed
      the intraoperative consumption of fentanyl, the postoperative consumption of
      morphine delivered using a PCA method, and the subjective pain intensity
      according to VAS score reported by patients in the early post-operative period.
      RESULTS: Out of 121 consecutive cases qualified for mastectomy, 112 women were
      allocated randomly to 1 of 2 groups--group A (bupivacaine) and group B (placebo).
      The final study group comprised 106 breast cancer cases. Between the groups, a
      statistically significant difference was observed with respect to: lower fentanyl
      consumption during surgery (p = 0.011), lower morphine (delivered by means of a
      PCA) consumption between the 4-12th postoperative hours (p = 0.02) and
      significantly lower pain intensity assessed according to VAS score at the 4th and
      12th hours after surgery (p = 0.004 and p = 0.02 respectively) for the group A
      patients. CONCLUSIONS: Preemptive analgesia application in the form of
      infiltration of the area of planned surgical incisions with bupivacaine in breast
      cancer patients undergoing mastectomy decreases post-operative pain sensation,
      limits the amount of fentanyl used during surgery, and reduces the demand for
      opiates in the hours soon after surgery.

PMID- 21959615
TI  - The selected genetic polymorphisms of metalloproteinases MMP2, 7, 9 and MMP
      inhibitor TIMP2 in sarcoidosis.
AB  - BACKGROUND: Increased activity of metalloproteinases may play a role in the
      initiation and propagation of inflammation in sarcoidosis, and may also be one of
      the factors responsible for the development of lung fibrosis. The aim of this
      study was to verify whether polymorphisms of MMP2 C-735T, MMP7 A-181G, MMP9 T
      1702A and tissue inhibitor of metalloproteinase (TIMP)2 G-418C predispose to
      sarcoidosis. MATERIAL/METHODS: The study included 139 patients with sarcoidosis
      and 100 healthy subjects. MMPs and TIMP2 mRNA were measured in peripheral blood
      lysate using real-time RT-PCR. DNA for genetic polymorphism was extracted from
      peripheral blood by GTC method. Protein concentrations in peripheral blood
      lysates were measured by ELISA, and MMP2 and 9 activities in BAL fluid were
      estimated by gel zymography. RESULTS: TT genotype in MMP9 T-1702A was more
      frequent in sarcoidosis (p<0.0001, OR = 13.71, 95% CI 7.02-26.80) and resulted in
      higher expression of MMP9 mRNA (p<0.0001). No differences were found between TT
      and AT/AA patients in terms of radiological stage, lung function test parameters,
      activity markers and the presence/absence of Lofgren syndrome. There were no
      differences in the distribution of MMP2, MMP7 and TIMP2 polymorphisms. Messenger
      RNAs, as well as protein concentrations of MMP2, 7, 9, and TIMP2 were elevated in
      patients with sarcoidosis (p<0.0001 for each). CONCLUSIONS: The TT homozygotes of
      MMP9 T-1702A genotype may be predisposed to sarcoidosis. Elevated MMP2, 7, 9, and
      TIMP2 mRNAs suggest their inducibility.

PMID- 21959616
TI  - Epiploic appendagitis in a 27-year-old man.
AB  - BACKGROUND: Epiploic appendagitis is an ischemic infarction of an epiploic
      appendage caused by torsion or spontaneous thrombosis of the central draining
      vein. Epiploic appendagitis is self-limited without surgery, and it is imperative
      for clinicians to be familiar with this entity. CASE REPORT: A healthy 27-year
      old man was admitted due to acute right lower quadrant abdominal pain. Physical
      examination showed focal abdominal tenderness with slight rebound tenderness.
      Laboratory tests showed leukocytosis and an increased serum C-reactive protein
      level. Computed tomography (CT) showed a fatty ovoid pericolonic mass measuring
      12 mm in diameter, with a circumferential hyperdense ring that abutted on the
      ascending colon and was surrounded by ill-defined fat stranding with a hyperdense
      ring. These findings were diagnostic of primary epiploic appendagitis. The
      patient was given high-dose antibiotics due to the secondary inflammation
      involving the parietal peritoneum. CONCLUSIONS: Epiploic appendagitis presents
      with an abrupt onset of focal abdominal pain and tenderness without significant
      guarding or rigidity; it is an uncommon and difficult diagnosis. With awareness
      of this condition, however, evaluation by CT can provide an accurate diagnosis of
      epiploic appendagitis, distinguishing it from conditions with clinically
      overlapping manifestations.

PMID- 21959618
TI  - Evaluation of differentiated neurotherapy programs for a patient after severe TBI
      and long term coma using event-related potentials.
AB  - BACKGROUND: This article examines the effectiveness of differentiated
      rehabilitation programs for a patient with frontal syndrome after severe TBI and
      long-term coma. We hypothesized that there would be a small response to relative
      beta training, and a good response to rTMS, applied to regulate the dynamics of
      brain function. CASE REPORT: M. L-S, age 26, suffered from anosognosia, executive
      dysfunction, and behavioral changes, after a skiing accident and prolonged coma,
      rendering him unable to function independently in many situations of everyday
      life. Only slight progress was made after traditional rehabilitation. The patient
      took part in 20 sessions of relative beta training (program A) and later in 20
      sessions of rTMS (program B); both programs were combined with behavioral
      training. We used standardized neuropsychological testing, as well as ERPs before
      the experiment, after the completion of program A, and again after the completion
      of program B. As hypothesized, patient M.L-S showed small improvements in
      executive dysfunction and behavioral disorders after the conclusion of program A,
      and major improvement after program B. Similarly, in physiological changes the
      patient showed small improvement after relative beta training and a significant
      improvement of the P300 NOGO component after the rTMS program. CONCLUSIONS: The
      rTMS program produced larger physiological and behavioral changes than did
      relative beta training. A combination of different neurotherapeutical approaches
      (such as neurofeedback, rTMS, tDCS) can be suggested for similar severe cases of
      TBI. ERPs can be used to assess functional brain changes induced by
      neurotherapeutical programs.

PMID- 21959617
TI  - Full trisomy 5 in a sample of spontaneous abortion and Arias Stella reaction.
AB  - BACKGROUND: Historically, 50% of spontaneously expelled abortuses have been
      thought to be chromosomally abnormal; about 60% are trisomies. In general,
      trisomy 16 is the most frequent chromosomal abnormality, followed by trisomy 21
      and trisomy 22. So far only 1 case of a female fetus with multiple congenital
      malformations associated with full trisomy 5 has been described. REPORT: We
      present a case of de novo full trisomy 5 in a spontaneous abortion sample. A
      young couple with normal constitutional karyotype experienced the second
      spontaneous abortion at 9 weeks of gestation, with the cytogenetic formula
      47,XX,+5 in all analyzed cells. CONCLUSIONS: The routine cytogenetic analysis of
      miscarriages is still an uncommon practice, but it can have a great impact on the
      management of couples with repeated pregnancy wastage. Besides of the obvious
      cost benefit for health care, such analysis would help the physician to decide
      about future patient management, as well as planning the genetic counseling.

PMID- 21959619
TI  - Spectral optical coherence tomography in a patient with type I sialidosis.
AB  - BACKGROUND: The aim of our study was to analyze spectral optical coherence
      tomography (SD-OCT) findings in a patient with clinical signs of sialidosis. CASE
      REPORT: Fluorescein angiography and spectral optical coherence tomography was
      performed in a 37-year-old woman using a SD-OCT device with axial resolution of 6
      um. Enzyme assay followed. The patient was diagnosed with type I sialidosis by
      enzymatic assay. Besides a normal angiogram, a thickened nerve fiber layer was
      observed on spectral optical coherence tomography. CONCLUSIONS: The thickened
      nerve fiber layer was probably caused by accumulation of metabolic products such
      as sialylated oligosaccharides and glycopeptides, suggesting that SD- OCT, due to
      its enhanced resolution, can be a useful tool for diagnosis of rare neurological
      conditions.

PMID- 21959620
TI  - Comment to: Novel Influenza A (H1N1) infection vs. common influenza-like illness:
      a prospective study; Voudoukis E, Pappas A, Panoutsopoulos A, Xynos K, Rozi F,
      Giannakopoulou K, Paulaki M, Stofa E, Seretis C, Lagoudianakis E, Andrianopoulos
      G; Med Sci Monit, 2011; 17(4): CR185-188.

PMID- 21959621
TI  - Are T2-weighted images more useful than T1-weighted contrast-enhanced images in
      assessment of postoperative sella and parasellar region?
AB  - BACKGROUND: The proper diagnosis and management of patients after surgery for
      pituitary tumors are of great importance in clinical practice. The purpose of
      this study was to investigate the magnetic resonance features of the
      postoperative sella with fast spin echo T2-weighted imaging and to evaluate the
      benefits of this sequence compared to the classically performed contrast-enhanced
      T1-weighted imaging at 1.5T unit. MATERIAL/METHODS: The study group consisted of
      101 patients who underwent resection of pituitary tumors. There were 58 women
      (57.4%), aged 22 to 75 (mean age, 52.67 years) and 43 men (42.6%), aged 21 to 79
      (mean age, 49 years). In all patients preoperative and multiple postoperative MR
      studies were performed. Post-contrast T1 and pre-contrast T2 images were
      interpreted by 2 independent readers (neuroradiologists). RESULTS: Contrast
      enhanced T1-weighted imaging was significantly superior to T2-weighted imaging in
      assessment of infundibulum (p<0.05). There was no statistically significant
      difference for each of readers between T1- and T2-weighted images regarding to
      the following features: visualization of residual pituitary gland (p = 0.062 and
      p = 0.368), contours of pituitary (p = 0.959 and p = 0.265), optic chiasm (p =
      0.294 and p = 0.843), and visualization of presence of residual tumor (p = 0.204
      and p = 0.169). T2-weighted images were significantly superior to contrast
      enhanced T1-weighted imaging with regard to visualization of contours of residual
      tumors (p<0.05). CONCLUSIONS: T2-weighted images may help to discriminate
      tumorous from non-tumorous involvement of the postoperative sella and the
      sphenoid sinus. T2-weighted images are also very useful for a long time after the
      resection in the postoperative evaluation of the implanted muscle with fascia.

PMID- 21959622
TI  - The clinical use of a fast screening test based on technology of capillary zone
      electrophoresis (CZE) for identification of Escherichia coli infection in
      biological material.
AB  - BACKGROUND: Escherichia coli is a Gram-negative bacterium which is a basic,
      symbiotic element of the physiological flora of the large intestine of humans and
      warm-blooded animals. However, in specific cases it may become a very dangerous
      pathogen (eg, diarrhoea, infection of the urinary tract, lungs, and generalized
      infections). Its early detection, as a cause of infectious disease, helps to
      achieve optimal treatment results; however, classical microbiological tests
      require at least 24 hours from sample taking to diagnosis. MATERIAL/METHODS: We
      present a unique solution based on CZE technologies enabling identification of E.
      coli presence in studied sample within half an hour. Altogether, 30 E. coli
      infected wounds and ulcerations were examined, comparing the results obtained by
      classical culture method with the result of capillary zone electrophoresis (CZE)
      electropherogram. RESULTS: The method, which does not require any preparation of
      the sample, achieved 86.7% sensitivity and 85%specificity in the examined
      clinical material (infections of surgical wounds). CONCLUSIONS: The obtained
      results enable reliable, very fast testing for E. coli as a pathogen.

PMID- 21959623
TI  - Molecular epidemical characteristics of Lamivudine resistance mutations of HBV in
      southern China.
AB  - BACKGROUND: Lamivudine (LMV), as the preferred oral drug for use in treatment of
      HBV, always results in development of resistance mutations after long-term
      treatment. In this study we investigated chronic hepatitis B (CHB) patients in
      southern China to determine whether different HBV genotypes affect the incidence
      of LMV resistance mutations. MATERIAL/METHODS: The study recruited 185 CHB
      patients living in southern China. Enzyme-linked immunosorbent assay was used to
      test for HBV serological markers, and HBV DNA was quantified by real-time PCR.
      Sequencing was performed to detect HBV genotypes and mutations. RESULTS: There
      were 49.19% (91/185) CHB patients with HBV resistant to LMV. Only 2 genotypes
      were found: B and C; 62.16% (115/185) of patients were infected with genotype B
      HBV and 37.84% (70/185) of patients were infected with genotype C HBV. The
      incidence rate of LMV resistance was not significantly different between genotype
      B and C (49.57% vs. 48.57%, P>0.05). For the mean age and sex ratio, no
      significant difference was found. The pattern of rtM204I alone was predominantly
      observed (36.26%, 33/91), followed by rtM204V+rtL180M (23.08%, 21/91). The
      overall incidence rate of rtM204I mutation in genotype B (45.61%, 26/57) was more
      frequent than that in genotype C (20.59%, 7/34) (45.61% vs. 20.59%, P<0.05), but
      the incidence rate of other mutation patterns was not significantly different
      between genotypes B and C. CONCLUSIONS: Our results emphasize that a LMV
      resistance test before treatment is of great importance in rational and optimal
      CHB therapy.

PMID- 21959624
TI  - Oxycodone and dexamethasone for pain management after tonsillectomy: a placebo
      controlled EMG assessed clinical trial.
AB  - BACKGROUND: Surface electromyographic (sEMG) study of post-tonsillectomy swallow
      evoked muscular reactions was performed in order to evaluate the efficacy and
      safety of oxycodone and dexamethasone in pain management after tonsillectomy.
      MATERIAL/METHODS: 90 randomly chosen operated adults were divided into three
      groups. Group 1 (n = 30) was treated with OxyContin (Oxycodone) injections; Group
      2 (n = 30) was treated with Dexacort (Dexamethasone), and Group 3 (n = 30) was a
      placebo group. Pain assessment included visual analogue scale (VAS) pain score
      and the EMG data like the timing, electric amplitude and graphic patterns of
      muscular activity during deglutition. We investigated masseter, infrahyoid and
      submental-submandibular muscles. Records from trapezius muscle were used for
      control. The results were compared with previously established normative
      database. The patients were tested 24 h after surgery. The sEMG data were
      compared with VAS pain score with regard to changes in clinical condition of the
      patients. RESULTS: Analgesia with oxycodone smoothed the recorded sEMG swallow
      peaks and increases time of deglutition. Dexamethasone normalized muscular
      activity in deglutition in cases with edema as detected by the EMG records.
      Statistically significant difference in muscle reactions was detected between the
      two Groups and the placebo group. CONCLUSIONS: Application of oxycodone
      significantly reduces the postoperative pain. Application of dexamethasone after
      tonsillectomy is advisable because of the reduction of postoperative morbidity
      while the reduction of the postoperative pain is secondary to the reduction of
      edema. SEMG might be used as an adjunctive measure of pain behavior via
      assessment of muscular reactions to pain and to analgesia.

PMID- 21959626
TI  - Magnetic resonance in studies of glaucoma.
AB  - Glaucoma is the second leading cause of blindness. It affects retinal ganglion
      cells and the optic nerve. However, there is emerging evidence that glaucoma also
      affects other components of the visual pathway and visual cortex. There is a need
      to employ new methods of in vivo brain evaluation to characterize these changes.
      Magnetic resonance (MR) techniques are well suited for this purpose. We review
      data on the MR evaluation of the visual pathway and the use of MR techniques in
      the study of glaucoma, both in humans and in animal models. These studies
      demonstrated decreases in optic nerve diameter, localized white matter loss and
      decrease in visual cortex density. Studies on rats employing manganese-enhanced
      MRI showed that axonal transport in the optic nerve is affected. Diffusion tensor
      MRI revealed signs of degeneration of the optic pathway. Functional MRI showed
      decreased response of the visual cortex after stimulation of the glaucomatous
      eye. Magnetic resonance spectroscopy demonstrated changes in metabolite levels in
      the visual cortex in a rat model of glaucoma, although not in glaucoma patients.
      Further applications of MR techniques in studies of glaucomatous brains are
      indicated.

PMID- 21959627
TI  - Carbohydrate-based pseudo-dipeptides: new ligands for the highly enantioselective
      Ru-catalyzed transfer hydrogenation reaction.
AB  - Ruthenium-complexes of novel carbohydrate based pseudo-dipeptide ligands
      effectively and selectively catalyze the reduction of a broad range of aryl-alkyl
      ketones under ATH conditions. Excellent enantioselectivities (>99% ee) are
      obtained using aminosugars as the sole source of chirality.

PMID- 21959629
TI  - New Zealand doctors and the pharmaceutical industry--time to cut the cord?

PMID- 21959625
TI  - Reciprocal regulation of cellular nitric oxide formation by nitric oxide synthase
      and nitrite reductases.
AB  - Our mini-review focuses on dual regulation of cellular nitric oxide (NO)
      signaling pathways by traditionally characterized enzymatic formation from L
      arginine via the actions of NO synthases (NOS) and by enzymatic reduction of
      available cellular nitrite pools by a diverse class of cytosolic and
      mitochondrial nitrite reductases. Nitrite is a major metabolic product of NO and
      is found in all cell and tissue types that utilize NO signaling processes.
      Xanthine oxidoreductase (XOR) has been previously characterized as a housekeeping
      enzyme responsible for cellular uric acid formation via enzymatic conversion of
      hypoxanthine and xanthine. It has become apparent that XOR possesses multi
      functional enzymatic activities outside the realm of xanthine metabolism and a
      small but significant literature also established a compelling functional
      association between administered sodium nitrite, XOR activation, and
      pharmacologically characterized NO transductive effects in positive
      cardiovascular function enhanced pulmonary perfusion, and protection against
      ischemia/reperfusion injury and hypoxic damage and oxidative stress. Similar
      positive vascular and cellular effects were observed to be functionally
      associated with mitochondrial aldehyde dehydrogenase and cytochrome c/cytochrome
      c oxidase. The profound implications of a reciprocal regulatory mechanism
      responsible for cytosolic and mitochondrial NO production are discussed below.

PMID- 21959630
TI  - The medicalisation of medical students.

PMID- 21959631
TI  - Satisfaction with life and depression among medical students in Auckland, New
      Zealand.
AB  - AIM: The aim of this study was to assess the satisfaction with life among
      undergraduate medical and other students in Auckland and identify associations
      with depression and anxiety disorders. METHODS: The study was conducted at The
      University of Auckland, New Zealand in 2008 and 2009. The sample population was
      derived from five undergraduate classes in four courses (medicine (two classes),
      nursing, health science and architecture). A battery of questionnaires including
      the Satisfaction with Life Scale (SWLS), Patient Health Questionnaire (PHQ) for
      depression and Generalised Anxiety Disorder Questionnaire (GAD) were administered
      to the cohort. Subgroup analysis between medical and other students were also
      carried out. RESULTS: A total of 778 students were eligible, and 594 (76.4%)
      students (255 medical, 208 health science, 36 nursing and 95 architecture)
      completed the questionnaire. The median age was 20 years (range 17-45) and women
      represented 67.2% (n=399) of the total group. The mean SWLS score for the total
      group was 24.9 (SD 6.4), with medical students on average having higher
      satisfaction with life compared to other students. The rate of depression (PHQ =
      10) and anxiety (GAD score = 8) among medical students was 16.9% (95% CI 12.2
      21.5) and 13.7% (95%CI 9.5-18.0) respectively. Female students had higher rates
      of depression and anxiety compared to males. A statistically significant moderate
      correlation between SWLS score and PHQ score [r = -0.37 (p<0.001)] and SWLS score
      and GAD score [r = - 0.23 (p<0.001)] were also observed. CONCLUSIONS: Medical
      students are more satisfied with life compared to other students. A significant
      proportion of students surveyed in this study have clinically significant
      depression and anxiety. Promoting positive wellbeing and improving satisfaction
      with life may enhance the quality of life as well as the social and academic
      performance of university students.

PMID- 21959632
TI  - Workload in a provincial New Zealand vascular surgery service.
AB  - AIM: There is increasing evidence that centralising complex surgical procedures
      improves mortality rates. The focus on mortality as the primary outcome measure
      overlooks every other aspect of a local surgical service that could be lost by
      centralisation. The aim of this audit was to assess the total vascular service
      provided in a provincial vascular surgical unit METHOD: This was a 12-month
      prospective audit of the vascular surgical service in Taranaki. All outpatient
      and inpatient vascular consultations and procedures carried out by a surgeon or
      interventional radiologist were identified. RESULTS: There were 181 inpatient
      admissions of which 121 (67%) were elective and 60 (33%) acute. There were 41
      (29%) non-operative admissions, while 140 (71%) required an operation as an
      inpatient. There were 967 total bed days for vascular patients with an average
      stay of 5 days (4-6 95% CI). There were 588 vascular outpatient consultations for
      396 patients. There were 201 (34%) new patient visits and 387 (66%) follow up
      appointments. CONCLUSION: Although the number of operations performed per
      population per year in Taranaki over the audit period was consistent with other
      reports, the number of major vascular cases did not meet suggested annual
      thresholds for minimising mortality. Despite this there was no evidence of
      increased mortality in any group. There was a large amount of non operative work
      which is not considered when focus is exclusively on mortality.

PMID- 21959633
TI  - Resource usage and outcomes in a facilitated discharge service in Christchurch,
      New Zealand.
AB  - AIM: To describe the type and level of support provided by a facilitated
      discharge team to frail older patients discharging from a 113-bed elderly
      rehabilitation hospital and the outcomes achieved. METHOD: Prospective data
      detailing reasons for referral, services provided and retrospective data on
      outcomes, were obtained to 90 days post discharge on visits to new patients
      during 21/2/08 to 15/7/08. RESULTS: Seventy-four patients (mean age 82, 58%
      female) were included. The mean duration of intervention was 19 days with the
      most common reasons for referral being poor mobility/falls risk, poor cognition,
      hygiene concerns. The average number of contacts was 6.5. Patients with the
      highest number of contacts were those referred with patient anxiety/low
      confidence (7.4), and family concern (8.4). The most common interventions were
      family contact and management of carer stress, liaison with medical staff.
      Unplanned readmission (within 90 days) occurred in 32% whereas 12% and 8% were in
      residential care or had died respectively. CONCLUSION: Managing the transition
      from hospital to home for older people requires a large range of interventions,
      particularly in this highly selected group. Unplanned readmission occurred in a
      third of this very frail elderly group, yet only 12% needed residential care,
      suggesting the reasons for readmission could be resolved. Patient or family
      anxiety resulted in more follow-up visits to patients, and inpatient teams should
      be mindful of this when planning discharges.

PMID- 21959634
TI  - Heater probe thermocoagulation for high-risk patients who show rebleeding from
      peptic ulcers.
AB  - AIM: To investigate whether heater probe therapy is effective for patients
      showing rebleeding from peptic ulcers. METHODS: We retrospectively reviewed the
      case profiles in our previous studies on endoscopic therapy for high-risk
      patients with peptic ulcer bleeding in the past two decades. We analysed the
      outcomes of 191 patients who showed rebleeding after initial endoscopic
      haemostasis and received endoscopic therapy with heater probe thermocoagulation.
      . RESULTS: A total of 191 patients showing rebleeding received heater probe
      thermocoagulation. After re-therapy, 158 patients (82.7%) achieved ultimate
      haemostasis. Twenty-five of the 33 patients who failed to achieve haemostasis
      received surgical intervention. Ten patients (5.2%) died within 1 month after re
      therapy. CONCLUSION: Heater probe thermocoagulation can be used as the first
      choice for management of patients showing rebleeding after initial endoscopic
      therapy.

PMID- 21959635
TI  - Clinical Science Investigation (CSI) Canterbury: surgical gown length and blood
      inside gumboots.
AB  - BACKGROUND: A gap between the bottom of gowns and the top of gumboots (commonly
      known as wellingtons or rubber boots outside of New Zealand) makes it possible
      for blood splashes to enter surgeons' gumboots and contact skin, putting them at
      risk of exposure to HBV, HCV and HIV. This study investigated the prevalence of
      blood splashes inside gumboots used by surgical staff at a single hospital.
      METHOD: Ninety-four pairs of gumboots (91 from male surgeons, 3 from female
      surgeons) from the hospital operating theatres were used in this study. Each pair
      of boots was visually inspected for internal contamination with blood. Possible
      stains were checked using urine dipsticks to confirm the presence of blood.
      RESULTS: Of the 94 pairs of gumboots checked, 55 pairs (58.5%) had blood staining
      on the inside lining. Eighty percent of blood stains were larger than 20 mm2.
      None of the female surgeons' gumboots were contaminated compared to 60% of the
      males' pairs. COCNLUSION: A large proportion of the gumboots used in operating
      theatres were contaminated internally with blood. The results of this study
      suggest that longer gowns should be available to health care workers in operating
      theatres to reduce internal contamination of gumboots and minimise the chance of
      exposure to body fluids.

PMID- 21959636
TI  - Laparoscopic cholecystectomy through the umbilicus--minimal access surgery gets
      more minimal.
AB  - We present the first three reported cases of single incision (through the
      umbilicus) laparoscopic cholecystectomy in New Zealand. The mean operating time
      was 108 minutes and all patients were discharged 24 hours after the procedure;
      they were all satisfied with their procedure and were keen to recommend it. We
      also provide a review of the international literature on this relatively new
      technique in New Zealand.

PMID- 21959637
TI  - Relationships between medical students and drug companies in New Zealand.
AB  - The relationships between doctors and drug companies have generated considerable
      global debate. Medical students are unique stakeholders in this discussion,
      although they are underrepresented in descriptive data. This article reviews
      international literature on the effects of drug company promotion, the effect on
      students, the New Zealand context and explores implications for New Zealand
      medical students. Creating an influence free environment to inform and involve
      students in the debate is a strong precursor to delivering gold standard patient
      care in the future.

PMID- 21959638
TI  - Right-sided chest pain in Poland syndrome.

PMID- 21959639
TI  - An unusual complication in a patient with Graves' disease.

PMID- 21959640
TI  - Medical image. Chronic alcoholic liver disease.

PMID- 21959641
TI  - Isotretinoin and abortion.

PMID- 21959642
TI  - Clarification on use of the term 'Dr' from the New Zealand Chiropractors'
      Association.

PMID- 21959643
TI  - From burnout to resilience: a general practice perspective.

PMID- 21959644
TI  - Off-label prescribing of atypical antipsychotic medications.

PMID- 21959645
TI  - Antimicrobial consumption data from New Zealand hospitals.

PMID- 21959646
TI  - A medical audit of practice management of diabetes in pregnancy at Gisborne
      Maternity Hospital's Obstetric Medical Service 2009-2011 (part 2).

PMID- 21959647
TI  - Beat Bowel Cancer Aotearoa response to GPs' opinions about the introduction of
      colorectal screening.

PMID- 21959648
TI  - Location of [60]fullerene incorporation in lipid membranes.
AB  - We confirmed that most C(60) fullerene units are located in the hydrophobic core
      of the lipid bilayer membrane in water-soluble lipid membrane incorporated C(60)
      (LMIC(60)) complexes using differential scanning calorimetry (DSC) and (13)C NMR
      spectra in the presence of radical labels.

PMID- 21959649
TI  - Salicylate intoxication with symptoms of septicaemia in a 17-month-old girl.

PMID- 21959650
TI  - [Primary meningococcal pericarditis with cardiac tamponade].

PMID- 21959651
TI  - Comparison of health state utility values derived using time trade-off, rank and
      discrete choice data anchored on the full health-dead scale.
AB  - Recent years have seen increasing interest in the use of ordinal methods to
      elicit health state utility values as an alternative to conventional methods such
      as standard gamble and time trade-off (TTO). However, in order to use these
      ordinal methods to produce health state values for use in cost-effectiveness
      analysis using cost per quality adjusted life year (QALY) analysis, these values
      must be anchored on the full health-dead scale. The paper reports on two
      feasibility studies that use two approaches to anchor health state utility values
      derived from discrete choice data on the full health-dead scale: normalising
      using (1) the TTO value of the worst state and (2) the coefficient on the 'dead'
      dummy variable. Health state utility values obtained using rank and discrete
      choice data are compared to more commonly used TTO utility values for two
      condition-specific preference-based measures; asthma and overactive bladder.
      Ordinal methods were found to offer a promising alternative to conventional
      cardinal methods of standard gamble and TTO. There remains a large and important
      research agenda to address.

PMID- 21959652
TI  - Toll-like receptors and their dual role in periodontitis: a review.
AB  - Innate immunity is the first line of host defense and represents inherited
      resistance to infection. Innate immunity works through toll-like receptors
      (TLRs), which recognize the conserved molecular patterns on pathogenic bacteria
      known as pathogen-associated molecular patterns. The periodontium is a unique
      environment in which oral microorganisms are in constant contact with the host
      immune system. The TLRs present on gingival epithelial cells are continuously
      stimulated, resulting in production of cytokines and defensins that help to
      maintain oral health. If the epithelial barrier is breached, allowing invasion of
      bacteria into the underlying connective tissue, the TLRs on other resident and
      non-resident cells of the periodontium become activated. This leads to an
      exaggerated release of pro-inflammatory cytokines and other biological mediators,
      which may cause host tissue destruction. The present review examines the role of
      TLRs and their signaling in periodontal health and disease.

PMID- 21959653
TI  - Bovine teeth as substitute for human teeth in dental research: a review of
      literature.
AB  - The aim of this paper was to review in vitro and in situ studies that directly
      compared the use of bovine teeth as a substitute for human teeth in dental
      experiments. A PubMed search was conducted for papers published from 1953 to
      December 30, 2010 using the following keywords: "human bovine enamel" or "human
      bovine dentin" or "human bovine teeth". The abstracts of the studies resulting
      from the keyword search were read, and all papers that compared human and bovine
      teeth were fully read. Only original articles written in English and directly
      comparing human and bovine substrates were included in the review. The search was
      supplemented by manual searches of the reference lists from each identified
      paper. Out of 76 studies initially selected, 68 fulfilled the selection criteria
      for inclusion. The studies covered seven categories: dental morphology, chemical
      composition, physical properties, dental caries, dental erosion/abrasion,
      bonding/adhesive strength, and marginal microleakage. Inconsistent data exist
      regarding whether bovine teeth can be considered an appropriate substitute for
      human teeth in dental research. Morphological, chemical compostion and physical
      property differences between the two substrates must be considered when
      interpreting results obtained from any experiment using bovine tooth substrate.

PMID- 21959654
TI  - Effects of polishing on surface roughness, gloss, and color of resin composites.
AB  - This study evaluated the effects of polishing on surface roughness, gloss, and
      color of regular, opaque, and enamel shades for each of three resin composites.
      Two-mm-thick resin disks made with Estelite Sigma Quick, Clearfil Majesty, and
      Beautifil II were final polished with 180-, 1000-, and 3000-grit silicon carbide
      paper. Surface roughness, gloss, and color were measured one week after curing.
      Estelite Sigma Quick had significantly lower roughness values and significantly
      higher gloss values as compared with Clearfil Majesty and Beautifil II. The
      effects of surface roughness and gloss on color (L*a*b*) differed among resin
      composites and by shade. Correlation coefficients between surface roughness and
      L*a*b* color factors were generally high for Clearfil Majesty, partially high
      (i.e., between roughness and L*) for Beautifil II, and low for Estelite Sigma
      Quick. Correlation coefficients between gloss and L*a*b* color parameters were
      generally high for Beautifil II and low for Estelite Sigma Quick and Clearfil
      Majesty. However, for all resin composites, the values of the color differences
      between 3000-grit and 180-grit polishing groups for all shades were imperceptible
      by the naked eye.

PMID- 21959655
TI  - Gingival crevicular fluid prostaglandin E2 level as a predictor of preterm low
      birth weight: a pilot investigation.
AB  - Periodontal infections, which serve as a reservoir of inflammatory mediators such
      as prostaglandin E(2) (PGE(2)), may pose a threat to the fetal-placental unit and
      cause preterm delivery. This study was conducted to estimate the levels of PGE(2)
      in gingival crevicular fluid (GCF) and serum to explore the possible use of the
      GCF-PGE(2) level as a risk predictor of preterm low birth weight (PLBW). Twenty
      two pregnant female patients were selected for the study. Samples of GCF and
      serum were collected from each patient, and sampling was repeated at one month
      after parturition. The level of PGE(2) in GCF and serum was estimated using a
      commercially available ELISA kit (NeogenTM). The mean serum PGE(2) level was 4.4
      ng/ml and 1.64 ng/ml before and after parturition, respectively, and the
      difference was statistically significant (P < 0.001). The mean GCF-PGE(2) level
      was 5.8 ng/ml and 5.5 ng/ml before and after parturition, respectively, but the
      difference was not significant. There was positive correlation between the
      serumPGE(2) and GCF-PGE(2) levels, and there was a negative correlation between
      PGE(2) level and gestational age. The present findings suggest that there is a
      weak correlation between maternal GCF-PGE(2) level and birth outcome. Further
      clinical trials with a larger sample size are warranted for further investigation
      of the association between GCF-PGE(2) level and PLBW.

PMID- 21959656
TI  - Effect of laser irradiation conditions on the laser welding strength of cobalt
      chromium and gold alloys.
AB  - Using tensile tests, this study investigated differences in the welding strength
      of casts of cobalt-chromium and gold alloys resulting from changes in the voltage
      and pulse duration in order to clarify the optimum conditions of laser
      irradiation for achieving favorable welding strength. Laser irradiation was
      performed at voltages of 150 V and 170 V with pulse durations of 4, 8, and 12 ms.
      For cobalt-chromium and gold alloys, it was found that a good welding strength
      could be achieved using a voltage of 170 V, a pulse duration of 8 ms, and a spot
      diameter of 0.5 mm. However, when the power density was set higher than this,
      defects tended to occur, suggesting the need for care when establishing welding
      conditions.

PMID- 21959657
TI  - Factors associated with prevalence of dental caries in Brazilian schoolchildren
      residing in Japan.
AB  - Brazilian immigrants comprise the third largest ethnic group within the Japanese
      population. The aim of this cross-sectional study was to determine the factors
      associated with the prevalence of dental caries in Brazilian schoolchildren
      living in Japan. A total of 378 schoolchildren, aged between 6 and 14 years,
      attending Brazilian schools in Japan were included. Clinical data were collected
      according to World Health Organization criteria. Socioeconomic data, oral health
      behavior and diet information were collected through questionnaires. The
      correlation between associated factors and dental caries prevalence was analyzed
      using chi-square test and multiple logistic regression analysis. The percentage
      of caries-free schoolchildren was 61.90% and the mean DMFT was 1.28 +/- 2.22
      (mean +/- SD). The mother's educational level and previous access to dental care
      services in Brazil were strongly associated with caries experience (P < 0.05).
      This study indicated that these variables are risk factors associated with caries
      experience in a community of Brazilian schoolchildren residing in Japan.

PMID- 21959658
TI  - Associations between oral health behavior and anxiety about water fluoridation
      and motivation to establish water fluoridation in Japanese residents.
AB  - Since 1972, community water fluoridation programs have not been practiced in
      Japan. Risk perception among the population plays an important role in the
      implementation of water fluoridation programs. The oral health behavior of
      Japanese children has changed, especially due to recent increases among children
      in the use of fluoridated products and fluoride applications by dentists. The
      purpose of this study was to examine the associations between oral health
      behavior, risk perception, and the desire to implement water fluoridation among
      Japanese residents. We distributed a questionnaire survey (response rate: 92.8%)
      to mothers with children aged two or three years (n = 573). There was a
      correlation between anxiety and level of motivation to implement water
      fluoridation (Spearman coefficient: 0.355, P < 0.001). Exposure to various
      fluoride experiences was higher in the "not anxious" group. The motivation level
      was significantly higher in subjects who had a better understanding of the
      effectiveness of fluoride, those who used fluoride tooth paste, and those whose
      children received fluoride applications from dentists. We conclude that increased
      knowledge of and experience with fluoride might help decrease the perception of
      risk and increase motivation for implementing water fluoridation among the
      general public.

PMID- 21959659
TI  - Temporomandibular joint injection with corticosteroid and local anesthetic for
      limited mouth opening.
AB  - It is unclear whether temporomandibular joint (TMJ) injections with local
      anesthetic and corticosteroid are an effective first-line management modality for
      patients with limited mouth opening. The purpose of this study was to determine
      the effectiveness of TMJ injections in patients with disc displacement without
      reduction (DDWOR), i.e. closed lock, at the University of Southern California
      Orofacial Pain and Oral Medicine Center. A retrospective chart review was
      conducted using a database of over 4000 patient records from 2003-2010. We
      identified 17 patients (16 female; 1 male) between the ages of 16 and 70 years
      who had been diagnosed with DDWOR and received a TMJ injection. Active mouth
      opening before injection ranged between 15 and 40 mm (average 29 mm), and active
      mouth opening after injection and manual mobilization ranged between 25 and 50 mm
      (average 39 mm). The average increase in mouth opening after injection and manual
      mobilization was 10 mm (P = 0.0004). TMJ injection with corticosteroid and local
      anesthetic is suitable as an alternative first-line management modality for
      DDWOR.

PMID- 21959660
TI  - Expression of connexins and the effect of retinoic acid in oral keratinocytes.
AB  - Differential expression of members of the connexin (Cx) gap junction multigene
      family permits formation of gap junctions with the varied physiological
      properties required by different tissues. The aim of this study was to
      characterize connexin expression and the influence of all-trans-retinoic acid
      (RA) in mouse gingival epithelial cells (GE1). The cells were treated with RA,
      and expression of Cxs was analyzed by immunofluorescence, reverse transcriptase
      polymerase chain reaction (RT-PCR), and real-time PCR. RT-PCR revealed that GE1
      cells expressed mRNA for Cx26, Cx30.3, Cx31.1, Cx32, and Cx43. In addition, real
      time PCR revealed that RA significantly decreased expression of Cx31.1 as
      compared with control. These results indicate that GE1 cells are useful in
      analyzing the expression of connexin molecules in oral keratinocytes from oral
      mucosal lesions.

PMID- 21959661
TI  - Association of testosterone and bone mineral density with tooth loss in men with
      chronic periodontitis.
AB  - A study was conducted to compare the mean testosterone and bone mineral density
      (BMD) levels in men with and without tooth loss. Two hundred three male subjects
      aged 30-65 years satisfying the study criteria were selected and then examined
      for bone mineral density, testosterone level, clinical attachment loss, probing
      pocket depth, tooth mobility and tooth loss due to periodontal disease.
      Statistical analysis was performed using the Statistical Package for Social
      Sciences (version 15.0) (SPSS Inc., Chicago, Ill, USA), and differences were
      considered to be significant at P < 0.05. Independent sample "t" test was used to
      compare the results, and receiver-operator curve (ROC) analysis was performed to
      obtain the cut-off. The mean testosterone level in subjects without tooth loss
      was 4.41 +/- 2.57, whereas that in subjects with tooth loss was 2.79 +/- 1.15 (P
      = 0.001). The mean BMD in subjects without tooth loss was 0.99 +/- 0.13, whereas
      that in subjects with tooth loss was 0.96 +/- 0.12 (P = 0.046). The testosterone
      level and BMD in subjects with tooth loss were significantly lower than those in
      subjects without tooth loss. Testosterone is a good predictor of tooth loss, but
      its efficiency decreases with increasing tooth loss. BMD is not a good predictor
      of tooth loss.

PMID- 21959662
TI  - Relationship between dental anxiety and pain perception during scaling.
AB  - Dental pain, anxiety and fear are important factors that prevent patients from
      seeking dental care. In this study, we aimed to evaluate the pain perception of
      patients during scaling and its relationship with dental anxiety. One hundred
      dental patients participated in the study. Pain levels after scaling were
      assessed with a Visual Analog Scale (VAS) and an Anxiety Questionnaire consisting
      of seven questions. The mean VAS score for the entire study group was 17.3 +/-
      13.8 with no statistically significant differences between gender and different
      age groups. The mean anxiety score was 11.66 +/- 4.17. This was significantly
      higher in women (P = 0.005), but there were no statistically significant
      differences between different age groups. There was a statistically significant
      correlation between VAS and total anxiety score (P < 0.001) as well as each
      question, except for questions number 3 and 4 in men. Patients were found to
      experience only limited pain during scaling. They were anxious because they
      expected pain, women being more anxious than men. Hence, dentists should seek to
      alleviate or reduce pain and anxiety related to treatment not only to
      successfully complete the treatment, but also to sustain and carry the patients
      into successful maintenance and patient recall.

PMID- 21959663
TI  - Comparison of three treatment options for painful temporomandibular joint
      clicking.
AB  - A randomized clinical trial was performed to evaluate the efficacy of three
      treatment options, including anterior positioning splint therapy, physical
      therapy, and physical therapy in addition to splint therapy, in terms of
      treatment outcome, in patients with painful temporomandibular joint clicking.
      Sixty patients suffering from acute pain and dysfunction were divided randomly
      into three treatment groups. Twenty patients underwent anterior positioning
      splint therapy (group I), 20 patients received solely physical therapy (group
      II), and 20 subjects received physical treatment in addition to splinting (group
      III). All patients were examined before and after the treatment using a visual
      analogue scale (VAS) and digital palpation of joint sounds. The data were
      analyzed using the Kruskal-Wallis, one-way ANOVA and Tukey tests at a
      significance level of P < 0.05. In comparison with the baseline, subjective pain
      was decreased significantly (P < 0.05) in all three groups. A significant
      difference was observed between groups I and II (P <0.05), whereas no significant
      difference was detected between groups II and III. Six patients in group III did
      not continue the treatment after physical therapy. The numbers of pain-free
      patients were 12 in group I, 5 in group II and 9 in group III. We observed a
      reduction in the frequency of joint sounds across the entire sample (P < 0.05).
      Anterior positioning splint therapy appears to be the best treatment method for
      reduction of pain and joint sounds in patients with TMD, compared with the other
      two methods studied.

PMID- 21959665
TI  - Odontogenic cysts: a retrospective study of 1227 cases in an Iranian population
      from 1987 to 2007.
AB  - Odontogenic cysts constitute a major part of oral pathological lesions, but
      little is known about their distribution patterns in various populations. In this
      retrospective study, patient records from the archive of the Department of Oral
      and Maxillofacial Pathology at the Faculty of Dentistry affiliated to the Tehran
      University of Medical Sciences were reviewed. Cases diagnosed as odontogenic cyst
      from 1987 to 2007 were selected and histopathologically re-evaluated to confirm
      the diagnosis. Patients' demographic information (age and sex) and location of
      the lesion were recorded and analyzed using descriptive statistics. From a total
      of 8529 files reviewed, the diagnosis of odontogenic cyst was confirmed in 1227
      cases (14.4%). The overall male to female ratio was 1.33:1. The patients' age
      ranged from 3 to 84 years with a mean of 28 years. 49% of cysts were found in
      maxilla and 50.4% in mandible. Radicular cyst was the most common type followed
      by dentigerous cyst, odontogenic keratocyst, residual cyst and paradental cyst.
      Lateral periodontal cyst, eruption cyst, glandular odontogenic cyst and gingival
      cyst of adults were also reported. The distribution pattern of odontogenic cysts
      in Iran is relatively similar to that in other parts of the world. The importance
      of complete clinical reports for final diagnosis of these lesions and routine
      follow-up examinations is emphasized.

PMID- 21959664
TI  - Additive effect of a diode laser on the antibacterial activity of 2.5% NaOCl, 2%
      CHX and MTAD against Enterococcus faecalis contaminating root canals: an in vitro
      study.
AB  - This in vitro study was performed to evaluate the effect of a diode laser and
      common disinfectants used in combination on mono-infected dental canals. One
      hundred and six single-rooted human premolars were prepared and contaminated with
      Enterococcus faecalis. After two weeks of incubation, samples were divided into
      two experimental groups (n = 48) and two control groups (n = 5). In the first
      group, the teeth were rinsed for 5 min with either sterile saline, 2.5% NaOCl, or
      MTAD, or for 1 min with 2% chlorhexidine gluconate (CHX). In the other group,
      samples were additionally irradiated with a 810-nm diode laser at 2 W output for
      5 * 5 s. Intracanal bacterial sampling was done, and the samples were plated to
      determine the CFU count. In the first group, 2.5% NaOCl was as effective as 2%
      CHX and significantly more effective than MTAD (P < 0.008). In the second group,
      either MTAD, 2% CHX or 2.5% NaOCl in combination with laser treatment had a
      similar effect. Absence of growth was seen only for MTAD plus laser treatment.
      Complete elimination of E. faecalis was seen only for the combination of MTAD
      with diode laser irradiation. Combination therapy with MTAD irrigation and diode
      laser irradiation, within the parameters used in this study, can be recommended
      as an effective treatment option for complete elimination of E. faecalis from the
      root canal system.

PMID- 21959666
TI  - Modeling the theory of planned behavior for intention to improve oral health
      behaviors: the impact of attitudes, knowledge, and current behavior.
AB  - The aim of this study was to test the efficiency of an extended model of the
      theory of planned behavior (TPB) in predicting intention to improve oral health
      behaviors. The participants in this cross-sectional study were 153 first-year
      medical students (mean age 20.16, 50 males and 103 females) who completed a
      questionnaire assessing intentions, attitudes, subjective norms, perceived
      behavioral control, oral health knowledge, and current oral hygiene behaviors.
      Attitudes toward oral health behaviors and perceived behavioral control
      contributed to the model for predicting intention, whereas subjective norms did
      not. Attitudes toward oral health behaviors were slightly more important than
      perceived behavioral control in predicting intention. Oral health knowledge
      significantly affected affective and cognitive attitudes, while current behavior
      was not a significant predictor of intention to improve oral health behavior. The
      model had a slightly better fit among females than among males, but was similar
      for home and professional dental health care. Our findings revealed that
      attitude, perceived behavioral control, and oral health knowledge are predictors
      of intention to improve oral health behaviors. These findings may help both
      dentists and dental hygienists in educating patients in oral health and changing
      patients' oral hygiene habits.

PMID- 21959667
TI  - Oral lesions associated with HIV infection before and during the antiretroviral
      therapy era in Ribeirao Preto, Brazil.
AB  - We estimated the prevalence of oral lesions associated with human
      immunodeficiency virus (HIV-OLs) before and during the antiretroviral therapy
      (ART) era. The first period was 1997, when many patients received two types of
      antiretroviral (ARV) drugs. The second study period was 2004 through 2008, when
      all patients were treated with ART (a combination of two or three classes of
      drugs, including protease inhibitors). A total of 148 and 388 seropositive
      participants were examined in 1997 and 2004-2008, respectively. The evaluation
      consisted of anamnesis and physical examination. The prevalence of HIV-OLs
      decreased between 1997 (60.1%) and 2004-2008 (29.9%). The HIV-OL responsible for
      the greatest reduction in prevalence between the two periods was oral
      candidiasis, of which erythematous candidiasis was the clinical form that
      decreased most, followed by pseudomembranous candidiasis. In conclusion, we
      observed a significant reduction in HIV-OLs, which was closely associated with
      the use of ART. In addition, among patients with a clinical diagnosis of AIDS, we
      confirmed a significant reduction in HIV-OL prevalence between 1997 and 2004
      2008.

PMID- 21959668
TI  - In vitro biocompatibility of novel Au-Pt-based metal-ceramic alloys.
AB  - The aim of this research was to evaluate the effect of individual metallic
      elements within experimental Au-Pt-based metal-ceramic alloys on in vitro
      biocompatibility. A binary Au-10 at.% Pt alloy (AP10) was designed as a parent
      alloy. Six ternary AP10-X (X = In/Fe/Sn/Zn) alloys and four quaternary (AP10-In2)
      Y (Y = Fe/Sn/Zn) with different compositions were cast into square plates with
      size 10X10X0.5 mm(3) and subjected to porcelain-firing thermal cycling. A
      commercial alloy was used as a control. In vitro biocompatibility was
      investigated using L929 murine aneuploid fibrosarcoma cell line. The test samples
      and cells were incubated at 37 degrees C in a 5% CO(2) atmosphere for 72 h.
      AlamarTM Blue Assay was carried out to determine the respiratory viability of
      cultures maintained in the presence of the different materials. The cell only
      control showed significantly higher levels of cell viability than all six of the
      ternary alloys and two of the four quaternary alloys, (AP10-In2)-Zn2.1 and (AP10
      In2)-Sn1.0 (P < 0.05). The quaternary alloys showed slightly higher levels of
      cell viability than the ternary alloys, with the exception of AP10-Sn0.9. No
      statistical differences were seen between the ternary and quaternary alloy
      groups. Acceptable cell viability was observed on the surfaces of all the alloys.

PMID- 21959669
TI  - Endodontic surgery failure: SEM analysis of root-end filling.
AB  - This study investigated the quality of root-end filling in cases of periapical
      lesions persisting after endodontic surgery. Ten patients requiring extraction of
      an endodontically treated tooth were included. The root-ends of extracted teeth
      were examined by scanning electron microscopy. Defects at the interface between
      the root-end filling and cavity margin were classified as ideal, imperfect (some
      marginal disruption) or inadequate (continuous marginal disruption involving >30%
      of the interface). Four cases were scored as imperfect, and six were scored as
      inadequate. A defective apical seal could favour continuous leakage of surviving
      bacteria and their by-products from the infected root canal system to periapical
      tissues, thereby sustaining inflammation.

PMID- 21959670
TI  - Management of an extensive invasive root resorptive lesion with mineral trioxide
      aggregate: a case report.
AB  - External invasive resorption is an uncommon but aggressive type of external
      resorption. This report outlines the management of an advanced case of external
      invasive resorption with mineral trioxide aggregate (MTA). The clinical and
      radiographic follow-up after 60 months revealed a functional tooth with a stable
      periodontal condition and no evidence of any further resorption.

PMID- 21959671
TI  - Bilateral supplemental maxillary central incisors: a case report.
AB  - Hyperdontia is a developmental anomaly that is hypothesized to arise from
      multiple causes. Supernumerary teeth may remain embedded in the alveolar bone or
      can erupt into the oral cavity. When such teeth remain embedded, they may cause
      disturbances to developing teeth. Erupted supernumerary teeth can cause aesthetic
      or functional problems, especially when situated in the maxillary anterior
      region. Before a definitive diagnosis and treatment plan can be developed, it is
      essential to clinically and radiographically enumerate and identify supernumerary
      teeth. Supplemental central incisors are rare and bilateral cases are even rarer:
      only five cases have been reported in the literature to date. We describe a case
      of bilateral supplemental maxillary central incisors and discuss the management
      of supernumerary teeth.

PMID- 21959672
TI  - The Valentines Trial: results of the first one week worldwide multicentre
      enrolment trial, evaluating the real world usage of the second generation DIOR
      paclitaxel drug-eluting balloon for in-stent restenosis treatment.
AB  - AIM: To assess the safety and efficacy of the second generation DIOR paclitaxel
      drug-eluting balloon (DEB) for in-stent restenosis in a real world setting in a
      prospective single-arm registry with 8-month clinical outcomes. METHODS AND
      RESULTS: In this "real world", international prospective registry, patients with
      in-stent restenosis (bare-metal stent and drug-eluting stent) were enrolled- in a
      unique study design- with a one week enrolment period, spread over 104 centres
      worldwide. Patients underwent predilatation with a regular balloon, with
      subsequent DEB inflation in the target lesion. Additional stenting of the target
      lesion was left to the operators discretion in case of suboptimal angiographic
      success (TIMI flow <3 and/or residual stenosis >30%). The primary endpoint was 6
      9-month major adverse cardiac events (MACE: all cause death, myocardial
      infarction, and target vessel revascularisation). A total of 250 evaluable
      patients were enrolled in a large web-based clinical research form and treated
      with the second generation DIOR DEB. Of these, 244 had 6-9 month clinical follow
      up, with a mean follow-up time of 7.5 months. The cumulative MACE rate at follow
      up was 11.1%, with 3 (1.2%) cardiac deaths, 1 (0.4%) non-cardiac death, 5 (2.0%)
      myocardial infarctions of which 2 (0.8%) periprocedural, 21 (8.6%) target vessel
      revascularisations, of which 18 (7.4%) target lesion revascularisations.
      CONCLUSIONS: In-stent restenosis treatment with the second generation DIOR DEB is
      safe and feasible, with high angiographic success and low target lesion
      revascularisation and overall MACE rates. Moreover this new and unique method of
      high speed and short duration multicentre study enrolment was very successful.

PMID- 21959673
TI  - Variables associated with outcome in patients with unilateral vestibular
      hypofunction.
AB  - BACKGROUND: Not all individuals with unilateral vestibular hypofunction (UVH)
      have fewer subjective complaints and improved function after vestibular
      rehabilitation. OBJECTIVE: To identify factors and/or combinations of factors
      that are strongly associated with rehabilitation outcome in patients with UVH and
      that ultimately can be used to develop models to predict outcome. METHODS: Data
      from 209 patients with UVH were analyzed. All patients participated in similar
      vestibular rehabilitation (5 weeks of home exercises and once-weekly clinic
      visits). Outcome measures included intensity of oscillopsia and dysequilibrium,
      balance confidence, perceived disability, percentage of time symptoms interfered
      with activities, gait speed, fall risk, and dynamic visual acuity (DVA).
      Bivariate correlation and regression analysis were used to determine
      relationships between baseline (pretherapy) measures and outcome at discharge.
      RESULTS: No baseline measure of subjective complaints (eg, symptom intensity)
      predicted improvement of physical function (eg, gait speed). Similarly, no
      baseline measure of physical function predicted improvement of subjective
      complaints. Certain patient characteristics, such as gender and time from onset,
      were not related to any outcomes. Most comorbidities did not affect outcome;
      however, anxiety and/or depression were associated with lower balance confidence
      and higher percentage of time for which symptoms interfered with activities at
      discharge. Baseline DVA and gait speed were associated with DVA and gait speed at
      discharge, respectively. Dynamic gait index (DGI) at discharge was affected by
      age, baseline DGI, and history of falls. CONCLUSION: These results provide
      insight into recovery of patients with UVH. Therapists can use this information
      in the development of expectations for patient outcome and treatment priorities.

PMID- 21959674
TI  - First permanent implant of nerve stimulation leads activated by surface
      electrodes, enabling hand grasp and release: the stimulus router neuroprosthesis.
AB  - BACKGROUND: . More than 150 000 neuroprostheses (NPs) have been implanted in
      people to restore bodily function in a variety of neural disorders. The authors
      developed a novel NP, the Stimulus Router System (SRS), in which only passive
      leads are implanted. Each lead picks up a portion of the current delivered
      through the skin by an external stimulator. OBJECTIVE: . The authors report on
      the first human implant of an SRS. METHODS: . The recipient was a tetraplegic man
      with bilateral hand paralysis. Three SRS leads were implanted in his right
      forearm to activate the finger extensors, finger flexors, and thumb flexor. A
      wristlet containing a surface stimulator and electrodes was used to pass trains
      of electrical pulses through the skin to each lead. Hand opening and grasp were
      controlled via a wireless earpiece that sensed small tooth-clicks and transmitted
      signals to the wristlet. RESULTS: . The current required to activate the muscles
      was less than half that required prior to implantation and below perceptual
      threshold. Maximal grip force and hand opening aperture were both larger using
      the SRS. The implanted leads have remained functional for 3 years. The recipient
      reported various tasks of daily life that improved during SRS usage. An
      electronic counter revealed mean monthly usage of 18.5 hours, equivalent to 55
      hours of continuous manual activity. CONCLUSIONS: . This first implant of the SRS
      indicates that it can be effective and reliable and has potential to provide an
      alternative to existing NPs.

PMID- 21959675
TI  - Randomized controlled trial of community-based dancing to modify disease
      progression in Parkinson disease.
AB  - BACKGROUND: Tango dancing has been effective in improving measures of physical
      function in people with Parkinson disease (PD). However, all previous studies
      were institution-based, tested participants on medication, and employed short
      term interventions. OBJECTIVE: To determine the effects of a 12-month community
      based tango program for individuals with PD on disease severity and physical
      function. METHODS: Sixty-two participants were randomly assigned to a twice
      weekly, community-based Argentine Tango program or a Control group (no
      intervention). Participants were assessed off anti-Parkinson medication at
      baseline, 3, 6, and 12 months. The primary outcome measure was the Movement
      Disorders Society-Unified Parkinson Disease Rating Scale 3 (MDS-UPDRS-3).
      Secondary outcome measures were the MDS-UPDRS-1, MDS-UPDRS-2, MiniBESTest balance
      test; Freezing of Gait Questionnaire (FOG_Q); 6-Minute Walk Test (6MWT); gait
      velocity for comfortable forward, fast as possible forward, dual task, and
      backward walking; and Nine-Hole Peg Test (9HPT). RESULTS: Groups were not
      different at baseline. Overall, the Tango group improved whereas the Control
      group showed little change on most measures. For the MDS-UPDRS-3, there was no
      significant change in the Control group from baseline to 12 months, whereas the
      Tango group had a reduction of 28.7% (12.8 points). There were significant group
      by time interactions for MDS-UPDRS-3, MiniBESTest, FOG_Q, 6MWT, forward and dual
      task walking velocities, and 9HPT in favor of the dance group. CONCLUSIONS:
      Improvements in the Tango group were apparent off medication, suggesting that
      long-term participation in tango may modify progression of disability in PD.

PMID- 21959676
TI  - Impaired motor learning by a pursuit rotor test reduces functional outcomes
      during rehabilitation of poststroke ataxia.
AB  - BACKGROUND: Motor learning is essential to gain skills with neurorehabilitation.
      OBJECTIVE: To investigate whether capacity for motor learning affects
      rehabilitation outcome and its relevant brain activation in ataxic patients with
      stroke. METHODS: Twelve patients presenting with ataxia admitted for inpatient
      rehabilitation 2 to 3 months after infratentorial stroke and 6 control subjects
      performed 8 repetitions of 30-second pursuit rotor (PR) task. Cortical oxygenated
      hemoglobin (oxyHb) signals were measured using functional near-infrared
      spectroscopy. RESULTS: Both patients and controls learned the PR skill, although
      the gains in PR performance were significantly lower in patients. In patients,
      the less learning significantly correlated with smaller rehabilitation gains
      assessed by the Functional Independence Measure. The Fugl-Meyer score for
      coordination and balance did not change. Center of task-related increase of
      cortical oxyHb signals shifted from the presupplementary motor area (preSMA) to
      the supplementary motor area (SMA) with task repetitions in controls but not in
      patients. Accordingly, serial changes of ratio of oxyHb increase in the preSMA to
      SMA (preSMA/SMA ratio) were significantly different between the groups. In
      patients and controls, gains in PR performance and changes of the preSMA/SMA
      ratio correlated. CONCLUSIONS: Impaired motor sequence learning by the PR task
      was correlated with reduced rehabilitation gains for ataxic patients with stroke.

PMID- 21959677
TI  - Prediction of illness severity in patients with major depression using structural
      MR brain scans.
AB  - PURPOSE: To develop a model for the prediction of Major Depressive Disorder (MDD)
      illness severity ratings from individual structural MRI brain scans. MATERIALS
      AND METHODS: Structural T1-weighted MRI scans were obtained from 30 patients with
      MDD recruited from two different scanning centers. Self-rated (Beck Depression
      Inventory; BDI), and clinician-rated (Hamilton Rating Scale for Depression,
      HRSD), syndrome-specific illness severity ratings were obtained just before
      scanning. Relevance vector regression (RVR) was used to predict the scores (BDI,
      HRSD) from T1-weighted MRI scans. RESULTS: It was possible to predict the BDI
      score (correlation between actual score and RVR predicted scores r = 0.694; P <
      0.0001), but not the HRSD scores (r = 0.34; P = 0.068) from individual subjects.
      BDI scores from the most ill patients were predicted more accurately than those
      from patients who were least ill (standard deviation of difference between
      predicted and actual scores 2.5 versus 7.4, respectively). CONCLUSION: These data
      suggest that T1-weighted MRI scans contain sufficient information about
      neurobiological change in patients with MDD to permit accurate predictions about
      illness severity, on an individual subject basis, particularly for the most ill
      patients.

PMID- 21959679
TI  - Hypermotility of an iris-fixated anterior chamber phakic intraocular lens due to
      nontraumatic iris laxity.
AB  - PURPOSE: Permanent immovability of phakic intraocular lenses (pIOLs) for the
      correction of high myopia is crucial in avoiding injury to the corneal
      endothelium and maintaining visual acuity. Unstable position of iris-fixated
      pIOLs due to traumatic or nontraumatic disenclavation of the haptic has been
      described previously. METHODS AND RESULTS: We report a different mechanism of
      repeated excessive implant motility in both eyes of a young woman who developed
      late nontraumatic elongation of the iris fibers to which an iris-claw pIOL was
      fixated. This led to increased motility of the pIOLs with blinking causing mild
      iritis. Subsequent bilateral successful re-enclavation to other iris fibers
      ameliorated these symptoms. After 2.5 years, these iris fibers, too, were
      elongated, causing excessive movements of the pIOLs and consecutive endothelial
      cell loss necessitating removal of the pIOLs. The etiology of this iris fiber
      laxity remains unclear. CONCLUSIONS: Surgeons should be aware of this rare
      potential complication.

PMID- 21959680
TI  - Initial PET/CT staging for choroidal melanoma: AJCC correlation and second
      nonocular primaries in 333 patients.
AB  - PURPOSE: To report on whole body positron emission tomography/computed tomography
      (PET/CT) screening for metastasis at diagnosis of primary uveal melanoma.
      METHODS: Since August 2003, 333 consecutive patients were diagnosed with uveal
      melanoma and underwent whole body screening for metastatic disease with PET/CT
      along with liver function tests and physical examination. Abnormal findings
      prompted further biopsies, blood tests, imaging, or clinical evaluations for
      confirmation. The presence of metastatic disease and second cancers were
      evaluated. RESULTS: Using the American Joint Committee on Cancer (AJCC) tumor,
      node, metastasis (TNM) 7th edition criteria, 104 tumors were classified T1 (31%),
      162 T2 (49%), 37 T3 (11%), and 30 T4 (9%). Seven of 333 (2.1%; 95% confidence
      interval [CI] 0.8-4.3) patients had metastatic melanoma. One tumor was a T3 and 6
      were T4. Thus, 3% of T3 and 20% of T4 melanomas were found to have metastases at
      the time of initial diagnosis. Ten patients (3.3%; 95% CI 0.9-5.5) had
      synchronous second cancers and 28 (8.4%) concurrent benign lesions. The most
      common metastatic sites were liver (7/7) and bone (2/7). DISCUSSION: This study
      suggests that PET/CT improves the yield of detecting both extrahepatic
      metastases, especially from tumors defined as AJCC-T4, and synchronous primary
      cancers, irrespective of the size of the uveal melanoma. With respect to liver
      metastases, PET/CT demonstrated high sensitivity and positive predictive values,
      indicating an overall better performance than conventional screening procedures.

PMID- 21959681
TI  - Choroidal neovascularization of optic disk melanocytoma treated with bevacizumab.
AB  - PURPOSE: To report a case of choroidal neovascularization (CNV) associated with
      optic disk melanocytoma successfully treated with bevacizumab. METHODS: A 63-year
      old man complained of visual impairment in his left eye. His visual acuity was
      0.9 OS. Fundus examination showed optic disk melanocytoma associated with serous
      retinal detachment and mild hemorrhage. Fluorescein and indocyanine green
      angiography revealed CNV adjacent to the optic disc. Intravitreous bevacizumab
      (IVB) was performed 3 times. RESULTS: Choroidal neovascularization and serous
      retinal detachment disappeared at 5 months after IVB. Visual acuity recovered to
      1.5 OS and has been stable for 1 year follow-up. No adverse events were found
      related to IVB. CONCLUSIONS: Intravitreous bevacizumab can be a beneficial
      treatment for CNV associated with optic disc melanocytoma.

PMID- 21959682
TI  - Changes in left ventricular preload, afterload, and cardiac output in response to
      a single dose of mannitol in neurosurgical patients undergoing craniotomy:  a
      transesophageal echocardiographic study.
AB  - BACKGROUND: Mannitol increases intravascular volume by withdrawing water from the
      brain and causes significant changes in stroke volume, cardiac output (CO),
      systemic vascular resistance, central venous pressure (CVP), and blood pressure.
      No previous studies have demonstrated changes in left ventricular (LV) preload,
      afterload, and CO using transesophageal echocardiography (TEE). METHODS: Fifteen
      adult patients undergoing elective supratentorial craniotomy received 20%
      mannitol 1.0 gm/kg over 15 minutes before dural opening. The following
      hemodynamic and TEE-derived parameters were recorded before and after the
      administration of mannitol: heart rate (HR), mean arterial pressure (MAP), CVP,
      LV end diastolic area (EDA), end systolic area, fractional area change, stroke
      volume, and CO. RESULTS: EDA and CVP significantly increased at 5 minutes
      (P=0.002 and <0.001) after mannitol infusion and remained insignificantly
      elevated till 15 minutes, thereafter returning to baseline values. CO also
      increased significantly at 5 and 15 minutes (P=0.001 and 0.013) and remained
      insignificantly elevated till 25 minutes, and thereafter returned to baseline
      values. A concomitant significant decline in systemic vascular resistance was
      observed at 5 and 15 minutes (P=0.002 and 0.008 at 5 and 15 min, respectively).
      Although EDA increased significantly at 5 minutes, there were no appreciable
      changes in MAP and HR throughout the study period. CONCLUSIONS: In conclusion, in
      patients undergoing craniotomy, TEE demonstrated that a single bolus dose of 20%
      mannitol (1.0 gm/kg) caused significant but short-duration alterations in LV
      preload, afterload, and CO without concomitant changes in hemodynamic variables
      (MAP/HR).

PMID- 21959684
TI  - Methods for removing glare in digital endoscope images.
AB  - BACKGROUND: Images produced by rod-lens telescopes used in minimally invasive
      surgery are brightest in the central region and darker at the periphery. To
      enable a clear view of the darker regions of the image, the intensity of light
      from the source usually is set to a high level. This often causes substantial
      reflection and glare from surgical tools and some tissue surfaces, which can be
      disturbing for the surgeon. This study investigated digital image processing
      methods in an attempt to reduce glare without introducing other adverse qualities
      into the images. METHODS: Two methods of reducing glare in local high-brightness
      regions of the image were evaluated. The first method reduced intensity by a
      fixed amount while also optionally introducing a slight color. The second method
      combined a proportion of the original intensity value with a proportion of a
      lower intensity value, again with an optional color bias. Two surgical video
      clips were modified with each of 13 different glare-reduction variants using
      these methods. These and the original sequence were played to a group of 10
      experienced surgeons for subjective assessment. RESULTS: The pixel-based methods
      both showed statistically significant improvements over the original version. The
      incorporation of a slight yellow bias was preferred to a straightforward gray
      level reduction. The simple approach of using a lower level of brightness alone
      was found to be unacceptable. Both new methods work in real time at normal video
      speeds. CONCLUSIONS: Antiglare methods have been found that reduce the perception
      of glare and are otherwise unobtrusive. This encourages further work to refine
      the preferred methods and to test them with a larger group over a wider range of
      video sequences. Clinical trials then will follow.

PMID- 21959683
TI  - Immunological effects of taxol and adryamicin in breast cancer patients.
AB  - Antineoplastic chemotherapy still consists in the major first-line therapeutics
      against cancer. Several reports have described the immunomodulatory effects of
      these drugs based on in vitro treatment, but no previous data are known about
      these effects in patients and its association with immunological-mediated
      toxicity. In this study, we first characterize the immunological profile of
      advanced breast cancer patients treated with doxorubicin and paclitaxel
      protocols, immediately after chemotherapy infusion. Our findings included an
      immediate plasmatic reduction in IL-1, IL-10, and TNF-alpha levels in doxorubicin
      treated patients, as well as high levels of IL-10 in paclitaxel patients.
      Further, it was demonstrated that both drugs led to leukocytes oxidative burst
      impairment. In vitro analysis was performed exposing healthy blood to both
      chemotherapics in the same concentration and time of exposition of patients,
      resulting in low IL-10 and high IL-1beta in doxorubicin exposition, as low TNF
      alpha and high IL-1 in paclitaxel treatment. Nitric oxide levels were not altered
      in both in vivo and in vitro treatments. In conclusion, our data revealed for the
      first time that the immediate effects of chemotherapy could be mediated by
      cytokines signaling in patients and that the results observed in patients could
      be a resultant of host immune cells activation.

PMID- 21959685
TI  - Impairment of sexual activity before and after endoscopic totally extraperitoneal
      (TEP) hernia repair.
AB  - BACKGROUND: In patients with inguinal hernias, sexual activity may be impaired
      due to hernia-related pain. Surgical repair may improve these complaints but can
      also lead to similar symptoms as a long-term complication of the operation.
      Endoscopic hernia repair is associated with less postoperative pain and earlier
      return to normal activities, but its effect on pain-related sexual function is
      unknown. In this study, the incidence and effect of pain related to sexual
      activity are evaluated before and after endoscopic totally extraperitoneal (TEP)
      hernia repair. METHODS: A hospital-based questionnaire study of pain-related
      sexual dysfunction was conducted in November 2009 in 500 male patients >=18
      years, who underwent TEP repair of a primary hernia between March 2006 and
      December 2008. The response rate was 77.2%. RESULTS: Pain of any severity during
      sexual activity was reported by 124 patients (32.1%) preoperatively and 35
      patients (9.1%) postoperatively. Only 2.3% of the 262 patients with no history of
      preoperative pain experienced moderate to severe (VAS 4-10) pain postoperatively.
      Pain impaired sexual function in 63 patients (16.3%) preoperatively and in 18
      patients (4.7%) postoperatively. The majority of patients who reported pain
      during sexual activity preoperatively (n = 102, 82.3%) had no pain
      postoperatively. The frequency of moderate to severe painful sexual activity
      decreased from 21.2% (preoperatively) to 3.4% after TEP repair (P < 0.001), and
      the frequency of moderate to severely impaired sexual function decreased from 6.0
      to 1.0% (P < 0.001). The preoperative presence of pain during sexual activity and
      chronic non-hernia-related pain syndromes were predictive for the occurrence of
      postoperative pain. CONCLUSION: Painful sexual activity, present in one third of
      patients with inguinal hernias, improved in the majority of patients following
      TEP hernia repair. Postoperatively, moderate to severe painful sexual activity
      occurred in 2.3% of the patients with no history of preoperative complaints.

PMID- 21959686
TI  - Single-incision laparoscopic total abdominal colectomy for refractory ulcerative
      colitis.
AB  - BACKGROUND: A three-stage restorative proctocolectomy with ileal pouch-anal
      anastomosis is the treatment of choice for the particularly debilitated patient
      with medically refractory ulcerative colitis (UC). Laparoscopic surgery has been
      shown to offer several advantages over the open approach in this setting. Single
      incision laparoscopic surgery is an emerging minimally invasive strategy
      representing a truly scarless procedure for the first surgical step, namely, the
      total abdominal colectomy (TAC). METHODS: Nine consecutive patients with
      medically refractory UC underwent a single-incision laparoscopic TAC between May
      and October 2010. All patients were on aggressive medical therapy with
      corticosteroids or immunosuppressors and were selected for this approach on the
      basis of their body habitus and the absence of relevant comorbidities. The whole
      operation was performed through a single access to the abdominal cavity, placed
      at the ostomy site marked preoperatively. RESULTS: Mean operating time was 142 +/
      23 min, with an estimate blood loss of 108 +/- 125 ml. No intraoperative
      complications or conversions to conventional laparoscopy or open surgery
      occurred. In all cases the postoperative course was uneventful. The return of
      bowel function was observed on postoperative day 1.7 +/- 0.7, and patients could
      tolerate a solid diet on postoperative day 3 +/- 0.5. The mean postoperative
      length of stay was 5.2 +/- 1.3 days. CONCLUSIONS: In our experience, a single
      incision laparoscopic approach to total abdominal colectomy for refractory
      ulcerative colitis has been shown to be safe and feasible. Initial results
      suggest that this technique can lead to improvements in short-term outcomes in
      selected patients.

PMID- 21959687
TI  - Evaluation of magnetic scope navigation in screening endoscopic examination of
      colorectal cancer.
AB  - BACKGROUND: Colorectal cancer is the most common cancer in Europe. Early
      diagnosis and treatment gives the patient a chance for complete recovery.
      Screening colonoscopies in the symptom-free patients are currently performed on a
      wide scale. The examinations are performed under local anesthesia which does not
      eliminate all discomfort and pain related to the examination. The aim of this
      study was to evaluate magnetic scope navigation in screening endoscopic
      examinations performed to detect early-stage colorectal cancer. METHODS: The
      study group consisted of 200 patients, aged 40-65 years, who were free from colon
      cancer symptoms. All patients underwent complete colonoscopy under local
      anesthesia. The equipment could be fitted with the scope that allows three
      dimensional observation of instrument localization in the bowel. The examination
      was performed by three experienced endoscopists, each of whom performed over
      5,000 colonoscopies. The patients were randomized to two groups: those whose
      equipment did not have 3D navigation (group I) and those whose equipment did have
      3D navigation (group II). Each group consisted of 100 cases matched by gender,
      age, and BMI. The authors compared the duration of introducing instrument to
      cecum, the pulse rate before the examination and at the time the instrument
      reached the cecum, and subjective pain evaluation by the patient on the visual
      analog scale. RESULTS: Group I consisted of 54 women and 46 men with a mean age
      of 54.6 years and mean BMI of 27.8 kg/m(2), and group II had 58 women and 42 men,
      mean age of 55.1 years and mean BMI of 26.4 kg/m(2). The average time it took for
      the instrument to reach the cecum was 216s in group I and 181s in group II (P <
      0.05). Pain measured on the 10-point VAS scale was 2.44 in group I and 1.85 in
      group II (P < 0.05). The results showed a significantly shorter time for the
      instrument to reach the cecum in group II and significantly lower pain intensity
      during the examination was reported by the group II patients. No significant
      differences were found in the pulse measurements between the groups (P = 0.5).
      CONCLUSIONS: 3D navigation during colonoscopy decreases the time for the
      instrument to reach the cecum and lowers pain intensity subjectively reported by
      the patients. The use of 3D and the possibility to observe instrument
      localization and maneuvers brings more comfort to the patients.

PMID- 21959688
TI  - Laparoscopic inguinal hernia repair: transabdominal preperitoneal (TAPP) versus
      totally extraperitoneal (TEP) approach: a prospective randomized controlled
      trial.
AB  - BACKGROUND: Minimal access approaches to inguinal hernia repair have added to the
      ongoing debate over the "best groin hernia repair." The present prospective
      randomized controlled trial was done to compare the totally extraperitoneal (TEP)
      and transabdominal preperitoneal (TAPP) techniques of laparoscopic inguinal
      hernia repair. METHODS: The present prospective randomized study was conducted
      between May 2007 and March, 2009 and included 100 patients suffering from
      uncomplicated primary groin hernia. Patients were randomized into group I (TEP)
      and group II (TAPP). Intraoperative variables and postoperative pain scores were
      recorded in a prestructured form. RESULTS: One hundred patients were included in
      the study (TEP, 53; TAPP, 47). Both groups were comparable in terms of
      demographic profile and hernia characteristics. The average operative time was
      higher in the TAPP group (p = 0.209). The pain scores at 1 h and 24 h after
      surgery and at 3-month follow-up were significantly higher in the TAPP group (p <
      0.05). The average follow-up was 30.5 months. In the TEP group, 37.8% of patients
      had seroma compared to 18.3% in the TAPP group (p = 0.021). However, there was a
      higher incidence of scrotal edema in the TAPP group (16 vs. 9, p = 0.009). The
      wound infection rates were equal (2% vs. 3%). There has been no recurrence in
      either group during the follow-up period of 44 months. Overall, the patients were
      more satisfied with TEP rather than TAPP (p < 0.05). CONCLUSIONS: In the present
      study, TEP had a significant advantage over TAPP for significantly reduced
      postoperative pain up to 3 months, which resulted in a better patient
      satisfaction score. The other intraoperative complications, postoperative
      complications, and cost were similar in both groups. In terms of results, both
      repair techniques seemed equally effective, but TEP had an edge over TAPP.

PMID- 21959691
TI  - [Contact dermatitis. Allergology must show its expertise].

PMID- 21959689
TI  - Long-term outcomes after transoral incisionless fundoplication in patients with
      GERD and LPR symptoms.
AB  - BACKGROUND: A retrospective study evaluated safety, symptom resolution, patient
      satisfaction, and medication use 1-2 years after transoral incisionless
      fundoplication (TIF) in patients with gastroesophageal reflux disease (GERD)
      and/or laryngopharyngeal reflux (LPR) symptoms. METHODS: Thirty-four patients
      with a confirmed diagnosis of GERD symptoms that were inadequately controlled by
      antisecretory medications, and who where either dissatisfied with their current
      therapy or not willing to continue taking medication, underwent TIF using EsophyX
      at our community-based hospital. Follow-up assessments were completed in 28
      patients. RESULTS: Median age of the study group was 57 (range = 23-77) years,
      BMI was 25.7 (18.3-36.4) kg/m(2), and 50% were female. All patients had
      documented chronic GERD for a median 5 (1-20) years and refractory symptoms to
      proton pump inhibitors (PPIs). Hiatal hernia was present in 75% (21/28) of
      patients, and 21% (6/28) had erosive esophagitis (LA grade A or B). TIF was
      performed following a standardized TIF-2 protocol and resulted in reducing hiatal
      hernia and restoring the natural anatomy of the gastroesophageal (GE) junction
      (Hill grade I). There were no postoperative complications. At a median 14-months
      follow-up, 82% (23/28) of patients were off daily PPIs (64% completely off PPIs),
      and 68% (19/28) were satisfied with their current health condition compared to 4%
      before TIF. Median GERD Health-Related Quality of Life scores were significantly
      reduced to 4 (0-25) from 26 (0-45) before TIF (P < 0.001). Heartburn was
      eliminated in 65% (17/26) and improved by >50% in 86% (24/28) of patients.
      Regurgitation was eliminated in 80% (16/20) of patients. Atypical LPR symptoms
      such as hoarseness, coughing, and throat clearing were eliminated in 63% (17/27)
      of patients as measured by Reflux Symptom Index scores. CONCLUSION: Our results
      in 28 patients confirm the safety and effectiveness of TIF, documenting
      symptomatic improvement of GERD and LPR symptoms and clinically significant
      discontinuation of daily PPIs in 82% of patients.

PMID- 21959692
TI  - [Psoriasis arthritis. An interdisciplinary challenge].
AB  - Psoriatic arthritis (PsA) is classified as a spondylarthropathy based on its
      clinical and serological characteristics. The clinical manifestations and the
      association with psoriasis or nail psoriasis have led, together with
      immunological characteristics, to a further differentiation. The
      pathophysiological and genetic understanding of this disease has advanced as a
      result of the development of new treatment strategies and targets in rheumatology
      and dermatology. Collaborative efforts and increasing multidisciplinary
      cooperation between rheumatologists and dermatologists have led to an increased
      awareness in early diagnosis and treatment. New treatment modalities have
      demonstrated significant efficacy in preventing radiologic progression resulting
      in amelioration of clinical symptoms, improvement of function and quality of
      life.

PMID- 21959693
TI  - Application of FT-Raman spectroscopy for in situ detection of microorganisms on
      the surface of textiles.
AB  - In this work we present the usefulness of FT-Raman spectroscopy for
      microbiological analysis of textiles. This technique was used for non-destructive
      identification of Escherichia coli bacteria on cotton and polyester fabrics. It
      was possible to discriminate between infected and non-infected materials.
      Moreover, this technique allowed detection of detergent traces as well as
      investigation of the influence of microorganisms on different textiles. Raman
      analysis supported by chemometrics (cluster analysis and principal component
      analysis) was shown to be a method for identification of textiles with inoculum
      of microorganisms in a short time. The results can be potentially used in the
      fabric industry and related areas.

PMID- 21959694
TI  - A classical polarizable model for simulations of water and ice.
AB  - We develop a classical rigid polarizable model of water for molecular simulations
      of water and ice. The model uses the Rowlinson five-site geometry: oxygen bearing
      the Lennard-Jones interaction and linearly polarizable point dipole, two
      positively charged hydrogens, and two massless negative charges placed
      symmetrically off oxygen so that the experimental dipole moment is reproduced.
      The target properties are the densities of water and ice Ih, diffusivity,
      enthalpies of fusion and vaporization, and the ice Ih melting point. The surface
      tension at lower temperatures is by 7% underestimated whereas the dielectric
      constant by 6% overestimated. Diffusivity and viscosity worsen at higher
      temperatures, although the Stokes radius is overestimated only by 2-7%. The ice
      Ih melting temperature is 260 K and the temperature of maximum density is 269 K.
      Rescaling the charges by a factor of 1.01 and Lennard-Jones energy by 1.0201
      improves the melting point and energy-related quantities but shifts the agreement
      of kinetic properties to higher temperatures. For the model we propose
      abbreviation POL4D.

PMID- 21959695
TI  - Cross-cultural adaptation and validation of the Korean version of the Oxford
      shoulder score.
AB  - BACKGROUND: The Oxford shoulder score (OSS) is being used increasingly and has
      been adapted cross-culturally in some Western countries. On the other hand, there
      are few validated translations of the OSS in Asian countries. This study
      translated and adapted cross-culturally the original OSS to produce a Korean
      version, and assessed the validity and reliability of the Korean version of the
      OSS (Korean OSS). METHODS: One hundred and five patients with shoulder pain
      caused by degenerative or inflammatory disorders completed the Korean OSS and
      Korean disability of arm, shoulder and hand (DASH). In addition, the pain score
      by a visual analog scale (VAS) during activity and at rest, subjective assessment
      of activities of daily living (ADL), the active range of motion (ROM), and
      measurements of the abduction strength (strength) were included in the validation
      process. RESULTS: There were no major linguistic or cultural problems during the
      forward and backward translations of the MHQ, except for a minor change due to
      cultural discrepancies in eating such as using a spoon and chopsticks by one
      dominant hand instead of a knife and fork by two hands. The internal consistency
      was high (Cronbach's alpha 0.91). The reproducibility test showed no significant
      difference (Intra-class coefficient 0.95). The construct validity, which was
      tested by the Pearson correlation coefficient revealed a strong correlation (r >
      0.6) between the Korean OSS against subscale of DASH disability/symptom, DASH
      work and ADL, as well as a moderate correlation (0.3 < r < 0.6) with the DASH
      sports/music, strength, ROM, pain during activity and pain at rest. CONCLUSION:
      The Korean OSS proved to be valid by demonstrating a significant correlation with
      the patient-based upper extremity questionnaire and clinical assessment. The
      application and evaluation of the instrument is feasible and understandable among
      patients in Korea.

PMID- 21959696
TI  - Determinants of outcome in operatively and non-operatively treated Weber-B ankle
      fractures.
AB  - INTRODUCTION: Treatment of ankle fractures is often based on fracture type and
      surgeon's individual judgment. Literature concerning the treatment options and
      outcome are dated and frequently contradicting. The aim of this study was to
      determine the clinical and functional outcome after AO-Weber B-type ankle
      fractures in operatively and conservatively treated patients and to determine
      which factors influenced outcome. PATIENTS AND METHODS: A retrospective cohort
      study in patients with a AO-Weber B-type ankle fracture. Patient, fracture and
      treatment characteristics were recorded. Clinical and functional outcome was
      measured using the Olerud-Molander Ankle Score (OMAS), the American Orthopaedic
      Foot and Ankle Society ankle-hindfoot score (AOFAS) and a Visual Analog Score
      (VAS) for overall satisfaction (range 0-10). RESULTS: Eighty-two patients were
      treated conservatively and 103 underwent operative treatment. The majority was
      female. Most conservatively treated fractures were AO-Weber B1.1 type fractures.
      Fractures with fibular displacement (mainly AO type B1.2 and Lauge-Hansen type
      SER-4) were predominantly treated operatively. The outcome scores in the non
      operative group were OMAS 93, AOFAS 98, and VAS 8. Outcome in this group was
      independently negatively affected by age, affected side, BMI, fibular
      displacement, and duration of plaster immobilization. In the surgically treated
      group, the OMAS, AOFAS, and VAS scores were 90, 97, and 8, respectively, with
      outcome negatively influenced by duration of plaster immobilization. CONCLUSION:
      Treatment selection based upon stability and surgeon's judgment led to overall
      good clinical outcome in both treatment groups. Reducing the cast immobilization
      period may further improve outcome.

PMID- 21959697
TI  - The effectiveness of a community playground intervention.
AB  - This study assessed whether an upgrade of playgrounds in a community was
      associated with changes in the physical activity of local children. The study
      used a natural experiment design with a local authority project to upgrade two
      community playgrounds as the intervention and a matched control community.
      Children's physical activity was measured by an Actigraph GT1M accelerometer worn
      for 8 days, enabling up to 6 days of data to be analyzed. A self-administered
      parent/guardian questionnaire was used to collect additional data, including
      perceptions of the neighborhood, school-travel modes, days involved in
      extracurricular activities, ethnicity, caregiver age, caregiver sex, household
      vehicle access, and household income. At baseline, 184 children (5-10 years old)
      participated. Of these, 156 completed the 1-year follow-up assessment (20% lost
      to follow-up). There was statistically significant evidence that change in mean
      total daily physical activity was associated with on an interaction between
      participant's body mass index (BMI) z-score and her or his community of residence
      (p = 0.006), with the intervention being associated with higher levels of
      activity for children with lower BMIs but lower levels for children with higher
      BMIs. Physical activity is not the only focus of local authority playground
      provision as playgrounds also have benefits for social development and
      fundamental movement skills. However, making sure that physical activity is
      always included in the design rationale and that playgrounds are designed to
      encourage and sustain physical activity could be a useful population health
      intervention. The effects of such interventions on different subgroups are of
      importance, especially if the effects differ over levels of BMI.

PMID- 21959699
TI  - Radiation dose in coronary artery angiography with 320-detector row CT and its
      diagnostic accuracy: comparison with 64-detector row CT.
AB  - AIM: The aim of this study was the comparison of image quality, diagnostic
      accuracy and radiation dose of ECG-gated volume scan mode of 320-detector row CT
      with 64-detector row CT. METHODS: A hundred and twenty patients receiving
      coronary artery CT angiography (CTA) were divided into two groups. Sixty patients
      in Group A underwent 64-detector row CTA; for the remainder, Group B, 320
      detector row CT was used. Conventional coronary angiography was then performed in
      all patients. In Group B, patients with a pulse <65 beat/min underwent a
      prospective ECG-gated volume scan using a 70-80% R-R phase window and 1-beat,
      whereas a 30-80% R-R phase window, 2-beat CT was performed in patients with a
      pulse >65 beat/min. RESULTS: In Group A, 247 vessels and 920 segments were
      assessed; in Group B, 242 and 906. In 320-detector row CTA, the coronary stenosis
      diagnosis' specificities were 98%, 96%, and 95% at the segmental, vessel, and
      patient levels, respectively (98%, 94%, and 92% in 64-detector row CTA); the
      negative predictive values were 99%, 98%, and 100% (98%, 97%, and 95% in 64
      detector row CTA). There was no significant difference in specificity or negative
      predictive values between the groups. The average effective radiation dose in
      Group B was lower than in Group A (P<0.001). In Group B, the dose for 48 patients
      with 70-80% R-R phase window, 1-beat scan, was lower than for the remaining 12
      patients (30-80% R-R phase window, 2-beat) (P<0.001). CONCLUSION: The 320
      detector CT reduces the radiation exposure by approximately 80% compared with 64
      detector CT, with similar diagnostic accuracy and image quality.

PMID- 21959700
TI  - Carbon dioxide insufflation versus air insufflation during endoscopic retrograde
      cholangiopancreatography under general anesthesia.
AB  - AIM: The aim of this paper was to evaluate the effect of carbon dioxide (CO2) vs.
      air insufflation on post-endoscopic retrograde cholangiopancreatography (ERCP)
      abdominal pain and distension. In addition, we investigated the changes in the
      partial pressure of end-tidal CO2 (PetCO2) and the partial pressure of arterial
      CO2 (PaCO2). METHODS: From October 2009 to January 2010, all patients admitted to
      our centre for ERCP were screened for enrollment; the patients recruited were
      randomised to CO2 or air insufflation. The patients were asked to rate their
      abdominal pain intensity and distension using a 100-mm Visual Analogue Scale
      (VAS) before, in the recovery room and at 1, 3, 6 and 24 hours after the ERCP.
      All anesthesiological and endoscopic details and complications were evaluated.
      RESULTS: We included 76 patients, 39 in the Air group and 37 in the CO2 group.
      The groups were similar for age, gender, indications and duration of the
      procedure. Post-procedure mean values of pain (in the recovery room and at 1, 3
      and 6 hours) and distension (at recovery room, and at 1 and 3 hours) according to
      the VAS were significantly reduced in the CO2 group as compared to the Air group.
      At baseline, the PetCO2 values were similar between the two groups while, during
      the ERCP, they increased significantly in CO2 group as compared to the Air group;
      these values were reduced by simply increasing the ventilation. CONCLUSION: CO2
      insufflation during ERCP significantly reduces post-procedural abdominal pain and
      distension. Increased PetCO2 and PaCO2 values remained within acceptable or
      readily controllable ranges.

PMID- 21959701
TI  - Dietary interactions and INR variability: retrospective evaluation of patients
      couples on oral anticoagulant therapy.
AB  - AIM: The association between dietary vitamin K intake and International
      Normalized Ratio (INR) variability in patients on oral anticoagulants treatment
      (OAT) has been evaluated in several studies. Changes in diet composition are
      known to lead to INR variability. We evaluated INR over time in married couples
      on OAT and non-cohabitant couples on OAT, to assess clinical relevance of the
      diet. METHODS: Among outpatients receiving OAT we selected 31 married couples.
      Husbands and wives were then matched by demographic and clinical characteristics
      to 31 men and 31 women on OAT not married nor living together. We analyzed 6,357
      INR measurements recorded from February 1998 to November 2009. RESULTS: We found
      similar average INR values within married couples and also within non-cohabitant
      couples. Using mixed models we confirmed INR differences between seasons and the
      slightly lower INR in non-cohabitant couples compared to married couples;
      although statistically significant, they were of marginal clinical significance.
      CONCLUSION: Within both married and non-cohabitant couples, we did not find
      statistically or clinically significant differences between men and women over
      time. The lack of INR differences over time within non-cohabitant couples
      indicates that diet is not an important determinant of INR over time. Also
      seasonal INR variations and differences between married and non-cohabitant
      couples were of little practical importance.

PMID- 21959703
TI  - Change Pain: changing the approach to chronic pain.
AB  - In Italy, chronic pain has a prevalence of about 26%, a rate that warrants
      efforts by specialists and primary care physicians to improve its treatment. From
      a study of various treatment systems, it is clear that a radical change in the
      approach to pain pathology is needed. To this end, the Change Pain International
      Advisory Board*, an international panel of experts, highlighted the limits to
      current treatment schemes and proposed new strategies. Among the criticalities
      are poor or inadequate communication between physician and patient, difficulty in
      qualitative and quantitative measurement of pain, management of adverse effects,
      and the "vicious circle" generated by current therapies, often the cause of poor
      compliance with pain treatment or discontinuation of analgesic therapy. A further
      limitation to current therapeutic practice is to consider pain intensity as the
      sole reference parameter in its treatment. In light of these considerations, the
      Advisory Board has drawn up a strategy to improve outcomes of pain therapy: 1) a
      shared therapeutic pact between physician and patient based on efficacious
      communication rather than on information alone; 2) identification of defined
      therapeutic objectives that allow for reaching a balance between reduction of
      pain and occurrence of adverse effects; 3) adoption of drug therapies that
      respond at least in part to an approach based on the pathogenic mechanism of pain
      rather than on pain intensity alone.

PMID- 21959704
TI  - [Bio-ecological control of chronic liver disease and encephalopathy].
AB  - Minimal encephalopathy was originally associated with chronic liver disease but
      is increasingly associated with most other chronic diseases and particularly with
      diabetes and also chronic disorders in other organs: kidneys, lungs, thyroid and
      with obesity. It is increasingly with dramatically increased and more or less
      permanent increase in systemic inflammation, most likely a result of Western
      lifestyle. Frequent physical exercise and intake of foods rich in vitamins,
      antioxidants, fibres, lactic acid bacteria etc in combination with reduction in
      intake of refined and processed foods is known to reduce systemic inflammation
      and prevent chronic diseases. Some lactic acid bacteria, especially Lb paracasei,
      lb plantarum and pediococcus pentosaceus have proven effective to reduce
      inflammation and eliminate encephalopathy. Significant reduction in blood ammonia
      levels and endotoxin levels were reported in parallel to improvement of liver
      disease. Subsequent studies with other lactic acid bacteria seem to demonstrate
      suppression of inflammation and one study also provides evidence of clinical
      improvement.

PMID- 21959705
TI  - [Vitamin D: from antirachitic factor to indicator of the general state of
      health].
AB  - Vitamin D has long been known for its effect of promoting intestinal absorption
      of calcium as well as bone mineralization and its deficiency leads to bone
      disease, rickets, once common in children. Recently, the receptor for vitamin D
      was found in cell types different from those commonly involved in calcium
      homeostasis and in vitro studies show that vitamin D is actively involved in
      cellular differentiation, also playing an antiproliferative, antiangiogenic and
      immunomodulatory function. In the meantime epidemiological observations showed an
      association between low levels of vitamin D and certain diseases such as cancer,
      cardiovascular diseases, diabetes and some immune system defects (allergy,
      asthma, multiple sclerosis); taken together these data suggests that contrasting
      deficiency of vitamin D will contribute to lower the risk of several major
      diseases. Data available in international scientific literature, however, does
      not allow definitive conclusions about the real benefits of vitamin D
      supplementation in the general population.

PMID- 21959706
TI  - Robot assisted laparoscopic prostatectomy. Striving for Trifecta outcomes in
      localised prostate cancer.
AB  - Radical prostatectomy (RP) is the gold standard treatment for localised prostate
      cancer and its oncological effectiveness has been demonstrated so far. With no
      doubt though, RP has significant potential morbidity and the selection of
      patients who will likely benefit from surgery while minimising the side effects
      of incontinence and erectile dysfunction is fundamental. Robot-assisted radical
      prostatectomy allows us to achieve oncological control, early continence and
      preservation of erectile function all in one. Thus, analysing its role is of
      utmost importance.

PMID- 21959707
TI  - Spontaneous rupture of fetal hydronephrosis: case report.
AB  - Hydronephrosis is the most common congenital anomaly observed with prenatal
      ultrasonography. Ureteropelvic junction obstruction (UPJO) is the most common
      cause of prenatal hydronephrosis. Spontaneous rupture has been reported in adults
      with severe hydronephrosis. There is no reported spontaneous rupture case in the
      fetus in the literature. A spontaneous ureteral rupture due to severe UPJO was
      reported in this case report. Prenatal ultrasound at 33 week gestation in a 21
      year-old pregnant woman, revealed a female fetus with grade IV hydronephrosis of
      the right kidney, suggestive of a UPJO. During the follow-up at XXXVIII week, 5
      cm cystic structure was not observed in right kidney. Mild ectasia was present in
      pelvicalyciel part which make us think about spontaneous rupture.
      Ultrasonographic examination after a week post-delivery revealed 15 mm
      pelvicalyciel ectasia on right side which persisted during the second control
      after 1 month. Vesicoureteral reflux was not detected during voiding
      cystourethrogram. Diuretic renography revealed loss of right renal function
      completely. Because there was not any complain or any clinical sign, surgery was
      not thought. Spontaneous follow-up was recommended.

PMID- 21959708
TI  - Vanishing bile duct syndrome in non-Hodgkin lymphoma: a case report.
AB  - Non-Hodgkin lymphoma (NHL) related vanishing bile duct syndrome (VBDS) is a rare
      condition that often leads to liver failure and death. A 64-year-old man with
      history of rheumatic heart disease complicated by steno-aortic insufficiency,
      mild mitral stenosis, atrial fibrillation, left kidney damage, bilateral
      glaucoma, left internal jugular vein thrombosis, bronchopneumonia, NHL type B
      (stage IV) treated with chemo and radiotherapy was admitted to our department for
      jaundice with predominantly cholestatic component. Liver biopsy allowed a
      diagnosis of VBDS and patient was treated with ursodesossicolic acid (UDCA) 20
      mg/kg/day associated with prednisone 1 mg/kg/day with a transient decrease of
      bilirubin and cholestasis, but a rapid worsening of general clinical conditions
      followed by severe acute liver failure (ALF), unresponsive to pharmacological
      therapy, leads to death our patient. In our case we supposed that this syndrome
      represents the paraneoplastic epiphenomenon of NHL with severe duct damage,
      related to lymphomatous release of toxic cytokines. In our clinical practice we
      must not forget that VBDS can be related to hepatic damage also induced during
      NHL. A special attention to abnormal liver function is necessary to diagnose this
      syndrome, because often the tests are interpreted as disseminated (stage IV)
      disease and not as a possible expression of VBDS which could, in some cases, be
      attenuated by UDCA and by steroids therapy.

PMID- 21959709
TI  - Institutional and home-based health care provided for elderly people in northern
      Italy in the nineteenth and twentieth centuries.

PMID- 21959710
TI  - Osteoporosis: prevention is also a question of the mind.

PMID- 21959711
TI  - Building knowledge about health services utilization by refugees.
AB  - The objective of this study was to compare the utilization of outpatient
      physician, emergency department and hospital services between refugees and the
      general population in Calgary, Alberta. Data was collected on 2,280 refugees from
      a refugee clinic in Calgary and matched with 9,120 non-refugees. Both groups were
      linked to Alberta Health and Wellness administrative data to assess health
      services utilization over 2 years. After adjusting for age, sex and medical
      conditions, refugees utilized general practitioners, emergency departments and
      hospitals more than non-refugees. A similar proportion in the two groups had seen
      a general practitioner within 1 week prior to their emergency department visit;
      however, refugees were more likely to have been triaged for urgent conditions and
      female refugees seen for pregnancy-related conditions than non-refugees. Refugees
      were more likely to have had infectious and parasitic diseases. Refugees utilized
      health services more than non-refugees with no evidence of underutilization.

PMID- 21959712
TI  - Hypertension risk assessment in the largest ethnic groups in Jordan.
AB  - Hypertension is the most common cardiovascular disease. No data exists on the
      health status of the largest ethnic groups in Jordan. Seven hundred ninety two
      Chechens and Circassians participated in this study. Two readings of systolic and
      diastolic blood pressure were taken from the left arm with the subject seated and
      the arm at heart level, after at least 5 min of rest, using standardized mercury
      sphygmomanometer. The mean of the two readings were taken as the individual's
      blood pressure. The overall prevalence rate of hypertension was 23.9%. Risk
      factors for hypertension were: family history (OR = 3.6, CI, 2.1, 6.3), female
      gender (OR = 2.5, CI, 1.7, 4.0), Dyslipidemia (OR = 2.3, CI, 1.5, 3.6), waist
      measurement above normal range (OR = 1.1, CI, 1.2-1.3) and older age (OR = 1.1,
      CI, 1.0-1.1). Public health efforts must be directed toward screening high risk
      individuals and intervening at early stage to improve health outcomes.

PMID- 21959713
TI  - Multifunctional Giant Amphiphiles via simultaneous copper(I)-catalyzed azide
      alkyne cycloaddition and living radical polymerization.
AB  - A novel class of chemically addressable, multifunctional Giant Amphiphiles was
      synthesized in excellent yields and polydispersity following simultaneous or
      sequential living radical polymerization and the click, copper(I)-catalysed azide
      alkyne cycloaddition (CuAAC). This new approach allows chemical tailoring of the
      biomacromolecules and in situ formation of nanocontainers.

PMID- 21959714
TI  - Evaluation of coronary artery in-stent patency using 64-slice computed
      tomography.
AB  - BACKGROUND: Surveillance conventional coronary angiography (CCA) is recommended
      after stent supported percutaneous coronary intervention due to the unpredictable
      occurrence of in-stent restenosis (ISR). We explored the ability of 64-slice
      computed tomography angiography (CTA) to detect ISR after stenting of the
      coronary artery and analyzed the factors influencing imaging quality. MATERIALS
      AND METHODS: Forty-five consecutive patients (29 stents) were examined by both
      CCA and 64-slice CTA after percutaneous coronary intervention. We analyzed the
      correlation between the image quality and heart rate, diameter, position, and
      stent-strut thickness. Compared with the CCA, the sensitivity, specificity,
      positive predictive value, and negative predictive value of 64-slice CTA for the
      detection of ISR were calculated. Between the patent group and ISR group,
      different computed tomography attenuation values of the in-stent lumen and artery
      5 mm proximal and distal to the stent were also analyzed. RESULTS: All stents
      were clearly visualized. With regard to the differences in heart rate, stent
      position, stent diameter, and stent-strut thickness among the different image
      quality groups, the P values were 0.47, 0.60, 0.04, and <0.01, respectively.
      Compared with CCA, the sensitivity, specificity, positive predictive value, and
      negative predictive value of 64-slice CTA were 100, 95.2, 88.9, and 100%,
      respectively. Between patent and ISR groups, the P values for the differences in
      CTA attenuation values of the in-stent lumen and artery 5 mm distal to the stent
      were 0.007 and 0.04, respectively. CONCLUSION: We found that 64-slice spiral CTA
      is a reliable noninvasive diagnostic method that can display the stent lumen
      clearly and is especially helpful for patient follow-up.

PMID- 21959715
TI  - Late angiograms ten years after transmyocardial laser revascularization.
AB  - We present the angiograms of a patient after transmyocardial laser
      revascularization (TMR), which were performed 10 years before by the application
      of holmium laser pulses. Thirteen years before the TMR procedure, the patient
      underwent coronary artery bypass graftings complicated by graft occlusion with no
      longer possibility of direct revascularization. Then, refractive angina required
      an alternative approach for symptom relief as the indirect revascularization by
      the application of the holmium laser pulses. Interestingly, the late angiograms,
      taken when the patient suffered from effort dyspnea for ongoing left ventricular
      dysfunction, showed a network of small vessels (absent before the TMR procedure)
      that supplies blood to the heart with no flow through the coronary arteries
      because of their complete occlusion. This is a historical presentation of the
      results of TMR to understand the effects of the indirect revascularization on the
      blood circulation through the heart over the long-term follow-up.

PMID- 21959716
TI  - Peritoneal dialysis is the best cost-effective alternative for maintaining
      dialysis treatment.

PMID- 21959718
TI  - Current evidence shows that survival outcomes are equivalent for dialysis
      techniques.
AB  - Studies that have analyzed survival between hemodialysis and peritoneal dialysis
      have showed heterogeneous outcomes for both techniques, and often confusing, also
      dependent on many factors. For this reason, it is necessary to know if there are
      real differences between the two treatments, to put the scientific evidence as a
      fundamental pillar in the choice of treatment, along with the clinical
      circumstances of individual patients, preferences and lifestyle of these. A
      comparative review of survival among dialysis techniques cannot avoid a basic
      methodological characteristics or attributes, such as appropriate designs such as
      observational studies with large cohorts, with incidents and no prevalent
      populations, with "intent to treat analysis "survival analysis and multivariate
      analysis with adjustments to the main comorbidity. We studied the nine classical
      main studies (incidents before 2002), presenting similar conclusions: there are
      no major differences between the techniques outcomes. When performing a
      stratification and adjustment for comorbidities, peritoneal dialysis has a
      equivalent or better prognosis in the nondiabetic group, less comorbidity and
      younger, almost all the publications, and hemodialysis in diabetics, older and
      more comorbid groups. The recent studies (including incidents after 2002),
      concluding a similar behavior for the survival HD: DP. Similarly, age and
      comorbidity influence the patient's outcomes almost identical to previous
      studies. In the last decade has seen an improvement in the prognosis of patients
      on dialysis, more pronounced in PD patients, both in the U.S., and Europe,
      Australia and in Spain (Andalusia analysis also). Finally, by multivariate
      analysis, we can show that patient survival on dialysis is much more influenced
      by conditions at the beginning of the treatment, as age, presence of diabetes or
      cardiovascular disease, rather than the type of technique of dialysis.  

PMID- 21959717
TI  - Chronic kidney disease--mineral and bone disorder: a complex scenario.
AB  - The chronic kidney disease-bone and mineral disorders (CKD-MBD) represents a
      dinamic area of research. Recently, new factors such as FGF-23 have been added to
      the classic list of regulators of bone metabolism, which include calcium,
      phosphorus, PTH and calcitriol. Vascular calcification, one of the most important
      complication of CKD-MBD is regulated by a complex variety of  promoters and
      inhibitors. The relationship between vascular calcification, bone loss and
      mortality, together with the existence of likely common signaling pathways are
      subject of interesting investigations.

PMID- 21959719
TI  - Economic impact of vitamin D treatment on chronic kidney disease patients.
AB  - During recent years, increasing recognition has been given to the endocrine
      action that vitamin D has on the extraskeletal system, and its deep involvement
      in CKD. This has meant that many vitamin D compounds (both nutritional and
      active) have been made available, with an important cost reduction. This review
      looks at the evidence available regarding the usefulness of different types of
      vitamin D (nutritional and active) for patients with stage 3-5 CKD and those
      undergoing dialysis. Emphasis is given to its usefulness to control
      hyperparathyroidism and its impact on morbidity and mortality. We also analysed
      pharmacoeconomic studies that have been published which compare active vitamin D
      metabolites. From this review, we are able to conclude that there is still not
      enough scientific evidence to be able to prefer one active vitamin D over
      another. In the meantime, doctors should follow the recommendations given in
      clinical practice guidelines, always taking into account their personal
      experience with patients. Furthermore, they must consider the economic impact
      that their treatment decisions may have.

PMID- 21959720
TI  - Hydration status assessment by multi-frequency bioimpedance in patients with
      advanced chronic kidney disease.
AB  - INTRODUCTION: Body composition assessment has the potential to improve the care
      of patients with chronic kidney disease (CKD). Whole-body multiple-frequency
      bioimpedance spectroscopy (BIS) appears to be a useful and appropriate technique
      for assessing hydration status and body composition in CKD patients. OBJECTIVE:
      The aims of this study were to determine the hydration status by BIS in patients
      with advanced CKD, and to analyse the association of body fluid status with
      common clinical and biochemical characteristics. The prognostic value of the
      phase angle at 50 KHz (PA) was also evaluated. PATIENTS AND METHODS: The study
      group consisted of 175 patients (66 +/- 14 year, 77 females) with eGFR < 40
      ml/min not yet on dialysis. Body composition was assessed by BIS (BCM,
      Fresenius). Hydration status was expressed as a percentage of the total body
      water (TBW). Patients were prospectively followed-up for a median of 481 days,
      and the main determinants of mortality were estimated by Cox regression analysis.
      RESULTS: The majority of patients (85%) showed a hydration status within +/- 5%
      TBW. Patients with oedemas or uncontrolled arterial hypertension showed mean
      estimate fluid overload significantly higher than that of the other study
      patients. Fluid overload was negatively associated with serum albumin levels,
      body mass index and urinary sodium/potassium ratio; and positively with male
      gender and diabetes. During the follow-up period, 16 patients died (9%). The main
      determinants of mortality adjusted for other potential covariates were: Davies
      comorbidity index (HR = 4.304; P = .001), and PA (per each  degrees ; HR = 0.491;
      P = .026). CONCLUSIONS: BIS may help identify changes in hydration status in CKD
      patients not fully appreciated by clinical or biochemical assessment. PA was a
      significant predictor of mortality in these patients.

PMID- 21959721
TI  - Recovering activity and illusion: the nephrology day care unit.
AB  - Day Care Units are an alternative to hospital care that improves more efficiency.
      The Nephrology, by its technical characteristics, would be benefit greatly from
      further development of this care modality. The objectives of this study are to
      present the process we have developed the Nephrology Day Care Unit in the Puerto
      Real University Hospital (C&aacute;diz, Spain). For this project we followed the
      Deming Management Method of Quality improvement, selecting opportunities,
      analyzing causes, select interventions, implement and monitor results. The
      intervention plan includes the following points: 1) Define the place of the Day
      Care Unit in the organization of our Clinical Department of Nephrology, 2) Define
      the Manual of organization, 3) Define the structural and equipment resources, 4)
      Define the Catalogue of services and procedures, 5) Standards of Care Processes.
      Protocols and Clinical Pathways; and 6) Information and Registration System. In
      the first 8 months we have been performed nearly 2000 procedures, which
      corresponds to an average of about 10 procedures per day, and essentially related
      to Hemodialysis in critical or acute patients, the Interventional Nephrology, the
      Clinical Nephrology and Peritoneal Dialysis. The development of the Nephrology
      Day Care Units can help to increase our autonomy, our presence in Hospitals,
      recover the progressive loss of clinical activity (diagnostic and therapeutic
      skills) in the past to the benefit of other Specialties. It also contributes to:
      Promote and develop the Diagnostic and Interventional Nephrology; improve the
      clinical management of patients with Primary Health Level, promote the Health
      Education and Investigation, collaborate in the Resources Management, and
      finally, to make more attractive and exciting our Specialty, both for
      nephrologists to training specialists.

PMID- 21959722
TI  - Serum cystatin C and microalbuminuria in the detection of vascular and renal
      damage in early stages.
AB  - BACKGROUND: The aim of this study was to assess serum cystatin C and urinary
      albumin in the early detection of impairment in cardiovascular and renal
      function. MATERIAL ANS METHODS: Cystatin C was quantified in sera from healthy
      people, moreover, cystatin C was quantified in a group of patients diagnosed with
      chronic kidney disease for predicting a measured glomerular filtration rate <60
      ml/min/1.73 m2. Finally serum cystatin C and microalbuminuria were measured in
      patients with increasing of risk of impairment in cardiovascular and renal
      function (hypertension, diabetes and hyperlipidemia). RESULTS: When the serum
      cystatin C was quantified in a group of risk, we observe as when being increased
      the cystatin C, the values of the glomerular filtration rate decreased (p <0.05),
      the cystatin values C were increased when increasing the age of the patients (p
      <0.05) and cystatin C values higher than 0.95 mg/l were not observed in patient
      smaller than 50 years old. In the group of risk, serum cystatin C was high
      regarding to the values obtained in healthy people in 27.6%, microalbuminuria in
      the 20.3% and both parameters were high in the 14.4% of patients with a
      glomerular filtration rate >90 ml/min/1.73 m2, while in patients with a
      glomerular filtration rate 60-90 ml/min/1.73 m2, cystatin C was high in the 51.7%
      and the microalbuminuria only in the 6.4%. CONCLUSIONS: Determinations of serum
      cystatin C associated to the quantification of urinary albumin in patients with
      cardiovascular risk can optimize the early detection of vascular and renal
      damage. Cystatin C can show vascular and renal damage in patients without urinary
      albumin.

PMID- 21959723
TI  - Early diagnosis and treatment of renal cell carcinoma of native kidney in kidney
      transplantation.
AB  - BACKGROUND: The frecuency of malignancies in renal transplant (RT) patients is
      increasing. Renal cell carcinoma (RCC) of native kidneys is one of the most
      frequent and its outcome can be more aggressive than in general population.
      OBJECTIVE: To evaluate the incidence and prognosis of RCC in renal transplant
      patients followed in our transplantation unit. METHODS: Between January 1997 and
      December 2009, 683 patients underwent kidney transplant at our hospital.
      Ultrasonography of the native kidneys was annually performed in all renal
      transplant patients. When suspect solid masses were found at ultrasonography,
      patients underwent computed tomography. If the suspicion was confirmed,
      nephrectomy was performed. RESULTS: 14 radical nephrectomies were performed in 12
      patients due to suspect CCR. In 11 nephrectomies (corresponding to 9 patients),
      anatomopathologic diagnosis was CCR (incidence 1.5%). Histologic stage was T1N0M0
      in all cases. In the other 3 RT, the diagnosis was complicated renal cyst. Those
      patients without carcinoma had polycystic kidney disease. The time on dialysis
      before CCR diagnosis was 36.7 +/- 24.3 months and the interval between RT and
      diagnosis was 39 +/- 25.8 months. After a mean follow-up of 58.6 +/- 38.6 months,
      the outcome of all cases has been excellent, without tumor recurrence.
      CONCLUSIONS: Annual renal ultrasonography plays a key role in the early diagnosis
      of CRR. The early treatment of this pathology is associated with an excellent
      prognosis in RT patients.

PMID- 21959724
TI  - Diagnostic accuracy of a hyperbolic model in predicting digoxin concentrations
      based on glomerular filtration rates.
AB  - BACKGROUND: Inappropriate doses and high serum concentrations of digoxin are
      highly prevalent in patients with renal impairment, and the drug dosage
      adjustment according to the glomerular filtration rate (GFR) is recommended. The
      aim of our study was to evaluate the dependence degree of digoxin total clearance
      (CL) on GFR, and the diagnostic efficiency of a predictive model for serum
      digoxin steady-state concentrations (Css) from estimated GFR by Cockcroft-Gault
      formula. METHODS: In 400 outpatients treated orally with digoxin, serum Css were
      determined (fluorescence polarization immunoassay from Abbott Laboratories), and
      total CL was calculated. The prediction of Css was carried out using a hyperbolic
      model developed by Konishi et al in Japan (J Clin Pharm Ther 2002;27:257), and
      the constants of the equation were modified for a Caucasian population. RESULTS:
      Only 26% of the digoxin CL interindividual variability may be explained by
      differences in GFR, and this fact is a serious limitation for the derived
      predictive models. A 65% diagnostic efficiency was obtained for original and
      modified hyperbolic models in the correct classification of predicted Css as
      subtherapeutic, therapeutic or supratherapeutic with respect to obtained Css
      concentrations. CONCLUSIONS: The diagnostic efficiency obtained in the prediction
      of serum digoxin concentrations from estimated GFR values is unacceptable for the
      drug dosage adjustment in clinical practice.

PMID- 21959725
TI  - Characteristics of patients registered with chronic renal disease in Castilla y
      Leon and survival analysis of transplanted patients and their grafts.
AB  - INTRODUCTION: Chronic kidney disease (CKD) is an important public health problem.
      Kidney transplantation is associated with increase survival and improvement of
      quality of life. OBJECTIVES: To describe the sociodemographic and clinical
      characteristics of patients registered in Castilla y Leon. To perform a survival
      analysis of transplant patients and their grafts. To evaluate survival depending
      on the transplant centre. METHODS: Descriptive study with data collected until 31
      December 2008 from the Registro de Dialisis y Trasplante Renal de la Comunidad de
      Castilla y Leon (REDI). The data was described differentiating prevalent and
      incidents patients. Survival data was assessed with the Kaplan-Meier method.
      RESULTS: On 31 December 2008, 2.498 patients were on Renal Replacement Therapy
      (RRT) (976.8 pmp); in 2008, 337 started treatment (131.8 pmp) and 94 received
      kidney transplant (36.8 pmp). The first cause of CKD for incident patients is
      diabetes (25.0%), followed by vascular diseases (18.1%). For prevalent patients:
      glomerulonephritis (16.5%) and diabetes (14.4%). Differences (p = 0.0021) were
      observed for the treatment initiation age, group of disease and prevalent
      patients (p <0.0001). During 11 years 1.062 transplants were performed in 1.012
      patients and 879 are still functioning (83%). In this period, the survival
      probability for the transplant patients is 81.076% (+/- 0.023), and for the 838
      patients with first functioning graft is 89.336% (+/- 0.016). Median graft
      survival is between 8.7 and 9.3 years (95% confidence). CONCLUSIONS: Most of the
      transplants during the last 11 years are still functioning. There are no
      differences when comparing graft survival at the approved centers in Castilla y
      Leon (p = 0.358).

PMID- 21959727
TI  - Kidney abnormalities in sickle cell disease.
AB  - Patients with sickle cell disease exhibits numerous kidney structural and
      functional abnormalities, changes that are seen along the entire length of the
      nephron. Changes are most marked in patients with homozygous sickle cell anemia,
      but are also seen in those with compound heterozygous states and the sickle cell
      trait. The renal features of sickle cell disease include some of the most common
      reasons for referral to nephrologists, such as hematuria, proteinuria, tubular
      disturbances and chronic kidney disease. Therapy of these conditions requires
      specialized knowledge of their distinct pathogenic mechanisms. Spanish
      Haemathology and Hemotherapy Association has recently publicated their Clinical
      Practice Guidelines of SCD management. Renal chapter is reproduced in this
      article for Nefrologia difussion.

PMID- 21959726
TI  - The nephrologist's role in metformin-induced lactic acidosis.
AB  - Metformin is an antihyperglycemic agent commonly used in diabetic patients. It is
      very effective and is able to reduce the plasma glucose and HbA1C. However, in
      some patients, specially those with comorbidities, metformin can provoke severe
      lactic acidosis with high morbimortality. Treatment of the lactic acidosis
      induced by metformin is based on the use of supportive general measures; in
      severe cases, procedures of extrarrenal purification like hemodialysis or
      continuous hemodiafiltration have been successfully used.

PMID- 21959728
TI  - Regression of vascular calcification in a patient treated with cinacalcet: a case
      report.
AB  - The purpose of this case report is to describe the regression of vascular
      calcifications (VC) in a patient with secondary hyperparathyroidism (SHPT) after
      having added cinacalcet to her treatment. We present the clinical case of a 48
      year-old woman with chronic renal failure secondary to tubulointerstitial
      disease. She was being treated with long-term haemodialysis (HD) and underwent
      two kidney transplants with transplantectomies. The patient presented with severe
      SHPT caused by parathyroid gland hypertrophy. The radiology test showed signs of
      VC in the radial and interdigital arteries, and VC in a linear arrangement were
      observed in both breasts on the mammography. Cinacalcet was added to her
      treatment with vitamin D derivatives and phosphate-binding agents, which resulted
      in a good control of mineral metabolism. The radiology test showed that the
      calcification in the interdigital artery had disappeared and that the bone
      appeared to be more structured. The mammography also showed regression of the VC.
      To conclude, cinacalcet may have potential for regression of VC in patients with
      SHPT.

PMID- 21959730
TI  - Commentary on: Treatment of HCV infection in chronic kidney disease.

PMID- 21959731
TI  - Cyclophosphamide-induced lupus flare?: the role of C4 and interferon-gamma in
      lupus flare.

PMID- 21959733
TI  - Metformin-induced lactic acidosis: usefulness of measuring levels and therapy
      with high-flux haemodialysis.

PMID- 21959734
TI  - Warning against unexpected medication in haemodialysis.

PMID- 21959735
TI  - Effect of fluorescein on renal function among diabetic patients.

PMID- 21959736
TI  - Multidisciplinary treatment. A therapeutic option to treat calciphylaxis.

PMID- 21959737
TI  - Varicella zoster virus: complications in an ANCA-positive vasculitis.

PMID- 21959738
TI  - Role of acute tubular necrosis with blood cast during endocapillary proliferative
      glomerulonephritis.

PMID- 21959739
TI  - Libman-Sacks endocarditis and severe aortic regurgitation in a patient with
      systemic lupus erythematosus in peritoneal dialysis.

PMID- 21959740
TI  - Intravascular haemolysis and renal failure.

PMID- 21959741
TI  - Atypical localization of tuberculosis in kidney transplants.

PMID- 21959742
TI  - Clinical case: Peritoneal dialysis patient with cloudy peritoneal fluid following
      administration of calcium antagonists.

PMID- 21959743
TI  - Chemical peritonitis in a patient treated with icodextrin and intraperitoneal
      vancomycin.

PMID- 21959744
TI  - Familial hemophagocytic lymphohistiocytosis in a pediatric patient diagnosed by
      brain magnetic resonance imaging.
AB  - Familial hemophagocytic lymphohistiocytosis (fHLH) is an autosomal recessive
      disorder characterized by proliferation and infiltration of several organs by
      activated lymphocytes and macrophages. Without allogeneic stem cell
      transplantation, fHLH is fatal. We describe a previously healthy 11-month-old boy
      with a rapidly progressive encephalopathy. An older brother died at 8 months
      following a subacute encephalopathy diagnosed as meningoencephalitis. The family
      history led to the suspicion of a metabolic disease, but metabolic studies were
      unrevealing. MRI showed multiple inhomogeneous signal abnormalities in the cortex
      and white matter, most prominent in the cerebral hemispheres and around the
      dentate nucleus. Gadolinium-enhanced T1-weighted images showed a multitude of
      enhancing foci, suggestive of perivascular enhancement. Based on MRI pattern with
      multiple lesions, perivascular enhancement and family history, fHLH was
      suspected. DNA analysis showed that the patient was compound-heterozygous for the
      c.445 G>A (p.Gly149Ser) mutation in exon 1 and the c.757 G>A (p.Glu253Lys)
      mutation in exon 2 of the perforin 1 gene. The patient was treated according to
      the international HLH-2004 protocol (dexamethasone, etoposide, cyclosporine,
      intrathecal methotrexate and prednisolone) followed by allogeneic cord blood
      transplantation. He showed a significant neurological and radiological
      improvement. The reported case demonstrates that MRI pattern recognition can lead
      to early diagnosis of fHLH, with subsequent adequate treatment.

PMID- 21959745
TI  - Cytotoxic not vasogenic edema is the cause for stroke-like episodes in propionic
      acidemia.

PMID- 21959746
TI  - Atlantoaxial rotatory fixation after ventriculoperitoneal shunting.
AB  - Ventriculoperitoneal (VP) shunting is a common neurosurgical procedure in the
      pediatric population. Atlantoaxial rotatory fixation (AARF) is not uncommon in
      this same group. We present the first reported case of AARF following a VP shunt
      procedure. A 10-year-old boy, with hydrocephalus and a left temporal arachnoid
      cyst since birth, underwent a revision of his VP and cystoperitoneal shunts. A
      second operation was performed 2 days later to optimize catheter placement.
      Postoperative neck pain was attributed to tunneling of the subcutaneous catheter.
      2 months after surgery, the child had minimal neck discomfort but maintained his
      head in a "cock-robin" position. Plain radiographs and computed tomographic (CT)
      images confirmed AARF. The child was admitted and placed in halo traction. After
      3 days of traction, analgesics, sedation, and muscle relaxants, anatomic re
      alignment of the C1-C2 vertebral complex was confirmed on CT scan. Following 3
      months of immobilization in a halo-vest apparatus, the halo was removed. At 8
      year follow-up, the clinical examination is normal and repeat imaging studies
      remain normal. Due to surgical positioning, and postoperative signs attributed to
      normal postoperative pain, an AARF was not initially recognized. This case
      represents the first time that AARF has been reported following a VP shunt
      procedure.

PMID- 21959747
TI  - Analytical basis for the determination of the lacunar-canalicular permeability of
      bone using cyclic loading.
AB  - An analytical model for the determination of the permeability in the lacunar
      canalicular porosity of bone using cyclic loading is described in this
      contribution. The objective of the analysis presented is to relate the lacunar
      canalicular permeability to a particular phase angle that is measurable when the
      bone is subjected to infinitesimal cyclic strain. The phase angle of interest is
      the lag angle between the applied strain and the resultant stress. Cyclic strain
      causes the interstitial fluid to move. This movement is essential for the
      viability of osteocytes and is believed to play a major role in the bone
      mechanotransduction mechanism. However, certain bone fluid flow properties,
      notably the permeability of the lacunar-canalicular porosity, are still not
      accurately determined. In this paper, formulas for the phase angle as a function
      of permeability for infinitesimal cyclic strain are presented and mathematical
      expressions for the storage modulus, loss modulus, and loss tangent are obtained.
      An accurate determination of the PLC permeability will improve our ability to
      understand mechanotransduction and mechanosensory mechanisms, which are
      fundamental to the understanding of how to treat osteoporosis, how to cope with
      microgravity in long-term manned space flights, and how to increase the longevity
      of prostheses that are implanted in bone tissue.

PMID- 21959748
TI  - The effect of ovary storage and in vitro maturation on mRNA levels in bovine
      oocytes; a possible impact of maternal ATP1A1 on blastocyst development in
      slaughterhouse-derived oocytes.
AB  - Since BSE testing of slaughtered cattle is obligatory in Japan, storage of
      ovaries at 15-20 C overnight in phosphate buffered saline has become a routine
      protocol in in vitro production (IVP) of cattle embryos. Ovary storage is known
      to reduce developmental competence of oocytes; however, its effects on oocyte
      gene expression have not been clarified yet. This study compared oocytes
      collected from stored slaughterhouse-derived ovaries with those collected by Ovum
      Pick-Up (OPU) in terms of the expression of 20 selected genes to determine if
      ovary storage affects cellular processes at the molecular level. Expression of
      mRNA in oocytes was assayed before and after in vitro maturation (IVM) by real
      time quantitative PCR. Maternal mRNA levels of genes were investigated in 2-cell
      stage embryos obtained from slaughterhouse oocytes to assess their roles for
      blastocyst formation. In immature OPU oocytes, genes related to metabolism
      (GAPDH), transporters (GLUT8, ATP1A1) and stress resistance protein (HSP70)
      showed significantly higher expression compared with oocytes derived from stored
      ovaries. During IVM, the expression of GDF9, GLUT8, CTNNB1 and PMSB1 was
      significantly decreased irrespective of oocyte source. Two-cell stage embryos
      cleaving at 22-25 h after in vitro fertilization (IVF) showed a significantly
      higher blastocyst formation rate and ATP1A1 gene expression level compared with
      those cleaving at 27-30 h after IVF. Our results reveal that storage of ovaries
      alters mRNA levels in oocytes. Correlation of Na/K ATPase ATP1A1 expression in
      IVP embryos at the 2-cell and 8-cell stages with their developmental ability to
      the blastocyst stage may suggest the importance of maternal mRNA of this gene
      during blastulation in embryos derived from slaughterhouse oocytes.

PMID- 21959749
TI  - Ag cluster-aptamer hybrid: specifically marking the nucleus of live cells.
AB  - Silver cluster-aptamer hybrids were mineralized via an artificially designed
      aptamer. The hybrids gave red emission when excited by light, and they
      successfully targeted the nucleus of live cells. This method is an effective
      approach to make cell target probes.

PMID- 21959750
TI  - Transfemoral implantation of an Edwards SAPIEN valve in a tricuspid bioprosthesis
      without fluoroscopic landmarks.
AB  - AIMS: We describe the first report of an Edwards SAPIEN valve implanted in a
      tricuspid bioprosthesis from the femoral vein. We highlight the feasibility of
      this previously avoided approach and the techniques involved. METHODS AND
      RESULTS: A 61-year-old woman with multiple valve replacements for rheumatic heart
      disease presented with NHYA IV dyspnoea secondary to a severely stenosed
      tricuspid bioprosthesis. After failed aggressive medical therapy and surgical
      turn down, an Edwards SAPIEN XT valve was deployed in the tricuspid bioprosthesis
      via the right femoral vein. Adaptations to the standard transfemoral
      transcatheter aortic valve implantation (TAVI) technique included: (1) crossing
      the tricuspid bioprosthesis with a balloon floatation catheter; (2) temporary
      pacing wire in the coronary sinus rather than the right ventricle; (3) mounting
      of the SAPIEN XT valve in the reverse orientation to transfemoral TAVI; and (4)
      fine positioning of the final valve position pre-deployment by 3D
      transoesophageal echocardiography (3D TOE) alone due to complete radiolucency of
      the tricuspid bioprosthesis. The procedure was completed without complication and
      resulted in significant symptomatic improvement. CONCLUSIONS: Deployment of an
      Edwards SAPIEN valve in a tricuspid bioprosthesis via the femoral vein is
      feasible and, with careful adaptations to established TAVI techniques, can be
      performed without complications and with good clinical response.

PMID- 21959751
TI  - Characterization of 5-HT(1A,B) and 5-HT(2A,C) serotonin receptor binding.
AB  - This unit describes assays for measuring the binding of radioligands to two major
      types of receptors for 5-hydroxytryptamine (5-HT or serotonin), 5-HT1 and 5-HT2
      receptors, in homogenates of brain tissue or cloned into cells in culture. The
      specific receptor subtypes covered are 5-HT(1A), 5-HT(1B), 5-HT(2A), and 5
      HT(2C). In addition, methodology for using quantitative autoradiography to
      measure radioligand binding to serotonin receptors in brain slices is described.
      Protocols are provided for characterization of both saturation and competition
      binding assays, and instructions for data analysis of these assays is also
      described. In addition, methodology is provided for the quantification (image
      analysis) of radioligand binding in brain tissue sections to determine receptor
      density, preparation of rat brain sections for quantitative autoradiography, and
      thionin staining of thaw-mounted tissue sections to define certain brain regions.

PMID- 21959752
TI  - Characterization of chemokine receptors.
AB  - This unit describes the procedures for measuring binding of a radiolabeled
      chemokine to chemokine receptors in cells or cell membranes. The whole-cell
      binding assay can be used for both purified leukocytes as well as transfected
      cell lines expressing chemokine receptors. Two basic protocols are described. The
      first is applicable to all cells expressing chemokine receptors, both primary
      cultures as well as recombinantly transfected cell lines expressing a single
      chemokine receptor. The second is used principally for transfected cell lines and
      measures chemokine binding to cell membranes using scintillation proximity assay
      (SPA) methodology, but does not require washing steps and thus is applicable to
      automated high-throughput screening strategies. An alternative procedure is also
      described which also uses SPA methodology to measure GTP-gamma-S binding to
      chemokine receptors in cell membranes. The two basic protocols can be used to
      determine the binding of compounds to chemokine receptors, while the alternate
      protocol determines the effects of compounds on the chemokine-stimulated
      activation of the receptor.

PMID- 21959754
TI  - Chondrocyte culture and assay.
AB  - Chondrocytes constitute the sole cell type found within cartilage, and control
      the formation and composition of cartilage. Cellular, biochemical and
      pharmacological studies of arthritis and other cartilage disorders have
      increasingly focused on chondrocyte function. Three methods are presented in this
      unit for culturing chondrocytes, and two assays are described that characterize
      proteoglycan synthesis, a key measure of chondrocyte function.Chondrocytes
      constitute the sole cell type found within cartilage, and control the formation
      and composition of cartilage.

PMID- 21959753
TI  - Characterization of calcium channel binding.
AB  - Voltage-dependent calcium channels are expressed in a variety of tissues
      including heart, muscles and brain. Saturation binding of a radioligand to the
      calcium channel is commonly used to characterize the expression level of the
      channel protein. Compound competition binding assay is a conventional screening
      method to determine the affinity of unlabeled compounds for the channel protein.
      This unit provides detailed experimental methods for two types of radioligand
      binding assays using [3H]PN200-100 and [125I](conotoxin MVIIA. Voltage-dependent
      calcium channels are expressed in a variety of tissues including heart, muscles
      and brain.

PMID- 21959755
TI  - Cellular assays of chemokine receptor activation.
AB  - This unit describes procedures for measuring the activation of chemokine
      receptors by their ligands. Chemokines are chemoattractant proteins and two
      assays are described for analyzing the chemoattractant properties (chemotaxis) of
      these proteins. Chemokine receptors are coupled to G proteins, and activation of
      the receptors results in the mobilization of intracellular Ca2+ stores. Two
      assays for the measurement of this activity are described which employ calcium
      sensitive dyes, one for adherent and one for non-adherent cells. In addition, an
      assay for quantitating chemokine receptor downmodulation and subsequent recycling
      events is described. The assays are applicable to both purified leukocytes and
      stably expressed recombinant chemokine receptors.This unit describes procedures
      for measuring the activation of chemokine receptors by their ligands.

PMID- 21959756
TI  - Characterization of matrix metalloproteinase inhibitors: enzymatic assays.
AB  - The matrix metalloproteinases (MMPs) are a family of tightly regulated proteases
      that are involved in the catabolic aspect of remodeling and maintenance of normal
      tissue, and more than 20 human MMPs have been identified thus far. The MMPs
      collectively degrade a broad range of protein components of the extracellular
      matrix. While some substrate overlap exists, individual MMPs have been shown to
      process certain substrates more efficiently than others. These differences raise
      the critical issue of whether broad-spectrum inhibitors, active against all MMPs,
      or selective inhibitors, targeted to a subset of enzymes, represent the optimal
      therapeutic strategy for a given disease. This suggests the need to assess the
      inhibition potency of test compounds across a range of MMP family members.
      Described in this unit is a method for the in vitro characterization of MMP
      inhibitors. The  is used to determine the potency of test compounds as inhibitors
      of 8 representative MMPs through the measurement of their inhibition of cleavage
      of a fluorogenic substrate. Since this substrate is efficiently hydrolyzed by all
      MMPs in the screening assays presented here, the method is convenient for
      assessing the selectivity of inhibitors against multiple enzymes. A describes the
      activation of MMP zymogens.

PMID- 21959757
TI  - In vitro enzymatic assays of protein tyrosine phosphatase 1B.
AB  - Many hormone or growth factor receptors signal via the activation of protein
      tyrosine kinases and phosphatases. Alteration of the phosphorylation state of
      tyrosine residues in certain proteins can directly regulate enzyme activity or
      cause formation of protein complexes necessary for transducing intracellular
      signals. Genetic and biochemical evidence also implicates protein-tyrosine
      phosphatases in several disease processes, including negative regulation of
      insulin receptor signaling at the level of the insulin receptor and perhaps in
      signaling at the IRS-1 level. The expression of protein tyrosine phosphatase-1B
      (PTP1B) is elevated in muscle and adipose tissue in insulin-resistant states both
      in man and rodents suggesting that PTP1B may play a role in the insulin-resistant
      state associated with diabetes and obesity. As described in this unit, PTP1B
      activity can be determined with the small molecule substrate, p-nitrophenyl
      phosphate (pNPP), in which the cleavage of the phosphate results in production of
      p-nitrophenol (pNP) and an increase in absorbance at 405 nm. Alternatively, PTP1B
      activity can be measured as described using model phosphotyrosyl-containing
      peptide substrates in which the release of free phosphate from the peptide is
      determined using a malachite green colorimetric assay.

PMID- 21959758
TI  - Histamine receptor assays.
AB  - This unit describes three standard in vitro bioassays for studying histamine H1,
      H2 and H3 receptors in isolated intact tissues removed from the guinea pig. Both
      the H1 and H3 receptor assays are based on preparations of the ileum, whereas the
      spontaneously beating right atrium assay is used for the H2-receptor.This unit
      describes three standard in vitro bioassays for studying histamine H1, H2 and H3
      receptors in isolated intact tissue.

PMID- 21959759
TI  - Prostanoid receptor assays.
AB  - Prostanoids, which include the prostaglandins (PGs) and thromboxanes (TXs),
      interact with a specific family of G-protein coupled receptors, of which there
      are known to be five distinct types, DP, EP, FP, IP and TP, each particularly
      sensitive to one of the five natural prostanoids, PGD2, PGE2, PGF2(, PGI2 and
      TXA2, respectively. Of these, it is known that the EP receptor comprises four
      well-characterized subtypes: EP1, EP2, EP3 and EP4. These receptor subtypes are
      widely distributed throughout mammals and other species, and show particularly
      high levels of expression in smooth muscle and blood platelets. Despite the fact
      that few of these preparations express a single receptor type/subtype in
      isolation, a range of useful smooth muscle and platelet assays for the various
      prostanoid receptors are available and are presented in this unit.

PMID- 21959760
TI  - Characterization of matrix metalloproteinase inhibitors: angiogenesis and tumor
      models.
AB  - Since the matrix metalloproteinases (MMPs) have an essential role in the process
      of tumor growth, invasion and metastasis, small molecule MMP inhibitors have the
      ability to modulate tumor progression in animals and the potential to be of
      therapeutic benefit to cancer patients. The antiangiogenic properties of MMP
      inhibitors can be assessed by the measurement of hemoglobin content of Matrigel
      plugs containing angiogenic growth factors introduced into the flanks of mice. A
      flank tumor growth model using B16 murine melanoma cells provides a useful means
      of determining the antitumor effects of MMP inhibitors as well as correlating
      efficacy with the concentration of drug in blood.

PMID- 21959761
TI  - Models of inflammation: adjuvant-induced arthritis in the rat.
AB  - Injection of adjuvant (Mycobacterium butyricum suspended in mineral oil) into
      rats produces an immune reaction that characteristically involves inflammatory
      destruction of cartilage and bone of the distal joints with concomitant swelling
      of surrounding tissues. Adjuvant-induced arthritis in rats is commonly used to
      evaluate compounds that might be of potential use as drugs for treatment of
      rheumatoid arthritis and other chronic inflammatory conditions. This unit
      describes a method for inducing arthritis by injecting adjuvant into the tail and
      evaluating a test compound for the ability to inhibit the inflammatory response.

PMID- 21959762
TI  - Enzymatic amplification of DNA by PCR: standard procedures and optimization.
AB  - This unit describes a method for amplifying DNA enzymatically by the polymerase
      chain reaction (PCR), including procedures to quickly determine conditions for
      successful amplification of the sequence and primer sets of interest, and to
      optimize for specificity, sensitivity, and yield. Hot-start methods are described
      which can greatly improve specificity, sensitivity, and yield. This protocol
      suggests some relatively inexpensive methods to achieve hot start, and lists
      several commercial hot-start options which may be more convenient, but of course
      more expensive. The unit has recently been updated to include new information on
      reagents to enhance the reaction, better cycling parameters, and innovations in
      robotics and high-performance thermocyclers.

PMID- 21959763
TI  - Mobility shift DNA-binding assay using gel electrophoresis.
AB  - DNA-binding assay using nondenaturing polyacrylamide gel electrophoresis (PAGE)
      provides a simple, rapid, and extremely sensitive method for detecting sequence
      specific DNA-binding proteins. Proteins that bind specifically to an end-labeled
      DNA fragment retard the mobility of the fragment during electrophoresis,
      resulting in discrete bands corresponding to the individual protein-DNA
      complexes. The assay described in this unit can be used to test binding of
      purified proteins or of uncharacterized factors found in crude extracts. This
      assay also permits quantitative determination of the affinity, abundance,
      association rate constants, dissociation rate constants, and binding specificity
      of DNA-binding proteins. Three additional protocols describe a competition assay
      using unlabeled competitor DNA, an antibody supershift assay, and multicomponent
      gel shift assays.

PMID- 21959764
TI  - Measurement of glutamate carboxypeptidase II (NAALADase) enzyme activity by the
      hydrolysis of [3H]-N-acetylaspartylglutamate (NAAG).
AB  - The peptide N-Acetylaspartylglutamate (NAAG) is hydrolyzed by N-Acetylated-alpha
      linked-acidic dipeptidase (NAALADase, glutamate carboxypeptidase II) into N
      Acetylated aspartate (NAA) and glutamate. Hydrolysis can be measured as described
      in this unit by employing radiolabeled NAAG (NAA-[(3)H]glu) as the substrate. The
      occurrence of NAALADase activity in a wide range of tissues has implications for
      a variety of physiological purposes. The assay described here is useful for the
      analysis of NAALADase activity and its inhibition in brain synaptosomal
      preparations, tissue homogenates and tissue culture cell pellets.

PMID- 21959765
TI  - Cytochrome p450 assays.
AB  - Cytochrome P450s (CYPs) play a major role in drug detoxification, and inhibition
      of CYP-mediated metabolism may lead to accumulation of toxic drug levels in the
      plasma. To prevent adverse drug-drug interactions, new drug candidates are
      routinely tested for their ability to inhibit these enzymes. This unit describes
      a variety of protocols for evaluating new chemical entities as inhibitors of CYP
      activity. An example protocol illustrates a high-throughput screening format
      using a fluorogenic probe, and a method for evaluating a test compound as a time
      dependent inhibitor of CYP is also described.

PMID- 21959766
TI  - Classic in vivo cancer models: three examples of mouse models used in
      experimental therapeutics.
AB  - Transplantable animal tumors have been associated with the discovery of most
      clinically active anticancer agents. They are still useful today in conducting
      detailed evaluations of new candidate anticancer drugs. Three protocols relating
      to transplantable experimental tumors are described in this unit. Included are
      the intravenously-implanted murine P388 leukemia, the subcutaneously-implanted
      murine B16 melanoma and two examples of subcutaneously-implanted human tumor
      xenografts, the LX-1 (lung) and MX-1 (breast) tumors.

PMID- 21959767
TI  - Overview of drug product development.
AB  - Drug product development, also called formulation chemistry, is the process of
      developing formulations for use in toxicology and clinical studies and for
      commercial supply. In this overview, the development process is described,
      including dosage forms for various delivery routes, toxicology formulation
      development, ingredient selection and manufacturing process development.

PMID- 21959768
TI  - Role of circulating fibroblast growth factor-2 in lipopolysaccharide-induced
      acute kidney injury in mice.
AB  - Fibroblast growth factor-2 (FGF-2) is an angiogenic growth factor involved in
      renal growth and regeneration. Previous studies in rodents revealed that single
      intrarenal injections of FGF-2 improved the outcome of acute kidney injury (AKI).
      Septic children usually show elevated plasma levels of FGF-2, and are at risk of
      developing AKI. However, the role of circulating FGF-2 in the pathogenesis of AKI
      is not well understood. We have developed a mouse model to determine how FGF-2
      released into the circulation modulates the outcome of AKI induced by
      lipopolysaccharide (LPS). Young FVB/N mice were infected with adenoviruses
      carrying a secreted form of human FGF-2 or control LacZ vectors. Subsequently,
      when the circulating levels of FGF-2 were similar to those seen in septic
      children, mice were injected with a non-lethal dose of LPS or control buffer. All
      mice injected with LPS developed hypotension and AKI, from which they recovered
      after 5 days. FGF-2 did not improve the outcome of AKI, and induced more
      significant renal proliferative and apoptotic changes during the recovery phase.
      These findings suggest that circulating FGF-2 may not necessarily prevent the
      development or improve the outcome of AKI. Moreover, the renal accumulation of
      FGF-2 might cause further renal damage.

PMID- 21959771
TI  - Criticality without self-similarity: a 2D system with random long-range hopping.
AB  - We consider a simple model of quantum disorder in two dimensions, characterized
      by a long-range site-to-site hopping. The system undergoes a metal-insulator
      transition--its eigenfunctions change from being extended to being localized. We
      demonstrate that at the point of the transition the nature of the eigenfunctions
      depends crucially on the magnitude of the hopping amplitude. At small amplitudes
      they are strongly multifractal. In the opposite limit of large amplitudes, the
      eigenfunctions do not become fractal. Their density moments do not scale as a
      power of the system size; instead our result suggests a power of the logarithm of
      the system size. In this regard, the transition differs from a similar one in the
      one-dimensional version of the same system, as well as from the conventional
      Anderson transition in more than two dimensions.

PMID- 21959769
TI  - Quality of life in children with vesicoureteral reflux.
AB  - Vesicoureteral reflux (VUR) is commonly diagnosed in children presenting with
      urinary tract infections. Antibiotic prophylaxis and ureteric surgery are
      standard treatments for these children. Our aim was to investigate whether health
      related quality of life (HRQOL) was altered in children treated for VUR. Children
      aged 1-5 years with grade III or higher VUR were identified through electronic
      records at the Stollery Children's Hospital. Parents of these children were
      mailed the TNO-AZL Netherlands Organisation for Applied Scientific Research
      Academic Medical Centre Quality of Life (TAPQOL) questionnaire. QOL scores for
      this group were compared with normative controls from the instrument's creators
      using the Mann-Whitney U test. Thirty-two of the 96 (33%) mailed surveys were
      returned. Eight children had surgery, and 19 were treated with antibiotic
      prophylaxis. When comparing the VUR group with the control group, we found that
      anxiety and social functioning scores were significantly better in patients with
      VUR (p < 0.01). The VUR group had worse scores in problem behavior, stomach
      complaints ,and communication (p < 0.01). This study reveals that children with
      VUR have a reasonable QOL when compared with controls. However, the diagnosis of
      VUR and its management does have an impact on gastrointestinal complaints,
      behavior, and communication, which may occur as a result of chronic medical
      intervention.

PMID- 21959772
TI  - Increased skin barrier disruption by sodium lauryl sulfate in mice expressing a
      constitutively active STAT6 in T cells.
AB  - Atopic dermatitis (AD) is a pruritic, chronic inflammatory skin disease that
      affects 10-20% of children and 1-3% of adults worldwide. Recent studies have
      indicated that the ability of Th2 cytokines, such as interleukin-4 (IL-4) to
      regulate skin barrier function may be a predisposing factor for AD development.
      The present studies examined the ability of increased Th2 activity to affect
      cutaneous barrier function in vivo and epidermal thickening. Mice that express a
      constitutively active Signal Transducer and Activator of Transcription 6
      (STAT6VT) have increased Th2 cells and a predisposition to allergic inflammation
      were used in these studies, they demonstrate that topical treatment with the
      irritant sodium lauryl sulfate (SLS) caused increased transepidermal water loss
      and epidermal thickening in STAT6VT mice over similarly treated wild-type mice.
      The proliferation marker Ki-67 was increased in the epidermis of STAT6VT compared
      to the wild-type mice. However, these differences do not appear to be linked to
      the addition of an irritant as control-treated STAT6VT skin also exhibited
      elevated Ki-67 levels, suggesting that the increased epidermal thickness in SLS
      treated STAT6VT mice is primarily driven by epidermal cell hypertrophy rather
      than an increase in cellular proliferation. Our results suggest that an
      environment with increased Th2 cytokines results in abnormal responses to topical
      irritants.

PMID- 21959773
TI  - [Anaphylactic reaction after soya intake in a patient with birch pollen allergy].
AB  - Patients with birch pollen allergy may suffer from severe anaphylactic reactions
      after ingestion of foodstuffs containing soya. The reason for this is
      similarities in protein structure between a major birch pollen allergen (bet v 1)
      and Gly m 4, a pollen-related protein in soya. A 65-year-old patient allergic to
      birch pollen developed an adverse systemic reaction after consumption of a soya
      containing drink. The diagnosis could be confirmed by in vitro and skin testing
      methods. Patients who suffer from birch pollen allergy should strictly avoid the
      intake of soya-containing foodstuffs.

PMID- 21959774
TI  - [Hearing loss determination and assessment of the reduction in earning capacity
      taking speech discrimination tests in noise into account].
AB  - BACKGROUND: In Germany the guideline for the hearing loss quantification and the
      resulting assessment of the reduction in earning capacity is the Konigsteiner
      Merkblatt (KM). The quantification depends on the results of the tone and speech
      audiogram in silence. However, speech discrimination tests in noise may provide
      additional information about the impairment of the ENT patients. Especially, the
      impairment of persons with a slight hearing loss, characterized by high-frequency
      hearing loss, in noisy environment can not be indicated by the measurement in
      silence, which is proposed in the KM. METHODS UND PATIENTS: The Gottingen
      sentence test in noise was applied as a supplement to the routine ENT procedures
      of the medical estimate in 135 test persons. Based on these measurement results a
      table for the percentage hearing loss in noise is defined. Furthermore, an
      integration of the hearing loss in noise in the assessment of the reduction in
      earning capacity is proposed in addition to the hearing loss in silence. RESULTS:
      Using the newly introduced hearing loss for speech in noise, a suitable
      assessment for persons with a slight hearing loss is achieved. By integrating it
      into the assessment procedure additionally to the hearing loss in silence, the
      hearing impairment of all patients can be rated depending on their speech test
      results in silence and in noise. In comparison to the results obtained by the KM,
      the new procedure does not lead to higher values for the proposed reduction in
      earning capacity in general, but instead seems to be equally suitable for all
      groups of patients.

PMID- 21959776
TI  - [Laser stapedotomy].
AB  - In addition to hearing aids, stapesplasty represents the standard treatment of
      otosclerosis-induced hearing loss. In this procedure, the stapes superstructure
      is replaced by a prosthesis that is attached to the long process of the incus and
      communicates through a perforation in the footplate with the perilymphatic space
      of the inner ear. The removal of the stapes superstructure and perforation of the
      footplate are the critical steps of this surgical procedure. With the
      introduction of laser-assisted perforation techniques, the surgical safety of
      this method has been improved compared to conventional techniques. KTP, argon, as
      well as diode, Er:YAG and CO(2) lasers are used for stapedotomy. By using the
      CO(2) laser in conjunction with a scanner system, the number of laser
      applications required for the perforation of the footplate has been markedly
      reduced. In contrast to other systems, a more reproducible perforation diameter
      of the stapes footplate is achieved with a CO(2) laser equipped with a scanner.
      Complications such as uncontrolled leakage of perilymph, irradiation of inner ear
      structures or the occurrence of pressure waves with subsequent damage to the
      inner ear can be reduced by using a CO(2) laser. In this review, the surgical
      technique of CO(2) laser stapedotomy, including clinically established variants
      and paying particular attention to the one-shot technique, are described and
      discussed in comparison to other laser systems.

PMID- 21959777
TI  - Determinants of specific food consumption in the Canary Islands (Spain).
AB  - The consumption of specific functional foods (FF) and some determinants of FF
      item selection were assessed using a questionnaire administered to 1112
      individuals in the Canary Islands (Spain). Food items considered were Milk
      products: easily digestible milk (or milk low in lactose), milk enriched with
      vitamins and/or minerals, skimmed milk with soluble fiber, milk with royal jelly,
      milk with modified fatty acids (omega 3), milk products low in fat, pro-biotic
      foods (yoghurt and fermented milk) and yoghurt with phytosterols; Cereals:
      fortified breakfast cereals, wholemeal cereals and energy bars; Drinks: juices
      and enriched drinks, stimulating drinks and isotonic drinks; DHA-enriched, low
      cholesterol eggs; Meat products: low salt sausages and cooked low fat ham; Fats:
      enriched margarine, margarine rich in phytosterols and sunflower oil rich in
      oleic acid; Condiments: iodated salt. These food items were organized into 7 FF
      groups (milk products, cereals, fortified drinks, DHA eggs, meat product, fats,
      condiments). The results indicated that the highest prevalence was fortified
      drinks (63.6%; 95% CI: 60.7-66.5). Overall FF consumption prevalence was 80.1%
      (95% CI: 77-83): single FF item consumption being rare. There were significant
      inter-group relationships, and some group intakes (milk products, cereals and
      drinks) were related to age but with no overall relationship between consumption
      and age. The education level was significantly related to the consumption of
      cereals, drinks, meat products and condiments (chi2 test p = 0.04). Some specific
      FF item consumption segregated with environment (rural or urban) but with no
      overall significant relationship between the FF group and environment or gender.

PMID- 21959775
TI  - [Possible molecular mechanisms of spontaneous remission in sudden idiopathic
      hearing loss].
AB  - According to current knowledge, it must be assumed that temporary idiopathic
      hearing loss and its spontaneous remission are based on mechanical and/or
      pathological alterations in the inner ear. The causal mechanisms might be based
      on inter-individual variations. Induced by dose-dependent activators, temporary
      as well as permanent damage might occur. Sudden hearing loss may be initiated by
      an increase in the local nitric oxide (NO) concentration. Spontaneous remission,
      i.e. functional restoration, can be explained by a local decrease in the NO
      concentration. In this context, regulatory systems such as the gap-junction
      system, blood vessels or synapses might be affected. In addition, alterations in
      the hormone level of estrogen and mineralocorticoids, as well as cellular
      glutathione and vitamin levels, might lead to temporary alterations in the inner
      ear. Recent experimental findings indicate a role for the shuttle protein
      Survivin in the spontaneous remission of sudden hearing loss.

PMID- 21959781
TI  - Functional analysis of Antirrhinum kelloggii flavonoid 3'-hydroxylase and
      flavonoid 3',5'-hydroxylase genes; critical role in flower color and evolution in
      the genus Antirrhinum.
AB  - The enzymes flavonoid 3'-hydroxylase (F3'H) and flavonoid 3',5'-hydroxylase
      (F3'5'H) play an important role in flower color by determining the B-ring
      hydroxylation pattern of anthocyanins, the major floral pigments. F3'5'H is
      necessary for biosynthesis of the delphinidin-based anthocyanins that confer a
      violet or blue color to most plants. Antirrhinum majus does not produce
      delphinidin and lacks violet flower colour while A. kelloggii produces violet
      flowers containing delphinidin. To understand the cause of this inter-specific
      difference in the Antirrhinum genus, we isolated one F3'H and two F3'5'H
      homologues from the A. kelloggii petal cDNA library. Their amino acid sequences
      showed high identities to F3'Hs and F3'5'Hs of closely related species.
      Transgenic petunia expressing these genes had elevated amounts of cyanidin and
      delphinidin respectively, and flower color changes in the transgenics reflected
      the type of accumulated anthocyanidins. The results indicate that the homologs
      encode F3'H and F3'5'H, respectively, and that the ancestor of A. majus lost
      F3'5'H activity after its speciation from the ancestor of A. kelloggii.

PMID- 21959782
TI  - Facile one-pot synthesis of gold nanoparticles and their sensing protocol.
AB  - This communication reports facile one pot synthesis of amoxicillin and sodium
      salt of amoxicillin stabilized gold nanoparticles (Au-NPs). Primarily the cyclic
      thioether linkage i.e. the thiozolidine ring of amoxicillin is utilized for
      sequestering Au(III). Fluorescence quenching of these clusters makes it an
      efficient protocol for sensing Cu(2+) at nano scale levels.

PMID- 21959783
TI  - Focal nodular hyperplasia--a review of myths and truths.
AB  - BACKGROUND: Focal nodular hyperplasia (FNH) is a benign hyperplastic lesion of
      the liver with no known malignant potential. It has generated much interest due
      to the frequency with which it presents with atypical features on radiological
      imaging. Often resulting in misdiagnosis. Moreover, the understanding of
      particular subtypes of this lesion at a molecular level has changed in recent
      years. This may have implications on how certain subtypes should be managed.
      PURPOSE: This review aims to analyse current literature pertaining to FNH and to
      provide clinically relevant advice regarding diagnosis and management.

PMID- 21959784
TI  - Turcot syndrome: a case report in an unsuspected setting.

PMID- 21959785
TI  - Therapeutic plasma concentrations of antidepressants and antipsychotics: lessons
      from PET imaging.
AB  - Therapeutic Drug Monitoring (TDM) of psychotropic drugs is strongly depending on
      the validity of recommended therapeutic plasma concentration reference ranges.
      Rational pharmacotherapy is based on the assumption that plasma concentrations
      are directly related to target occupancy by the respective drug. Here we show
      that positron emission tomography (PET) of molecular drug targets in the brain
      (neuroreceptors and transporters) allows for establishment of these
      relationships, thereby providing guidance for TDM services. Associations between
      brain target occupancy, plasma concentrations, and clinical effects and adverse
      reactions will be discussed for the most commonly used antidepressant and
      antipsychotic drugs.

PMID- 21959786
TI  - Therapeutic drug monitoring in child and adolescent psychiatry.
AB  - Psychopharmacotherapy in children and adolescents is characterized by an
      increased susceptibility for adverse events and an increased risk of ineffective
      treatment due to specific age-dependent and developmental characteristics in
      comparison to adults. Dosing in paediatric psychiatric patients requires careful
      handling, since the dose recommendations for adults can not simply be
      extrapolated to minors because of pharmacokinetic and pharmacodynamic
      differences. In addition, psychopharmacotherapy in children and adolescents is
      hampered by lack of high quality evidence on efficacy and safety in many
      indications and subsequently a high degree of off-label use. Therapeutic Drug
      Monitoring (TDM) is an established and useful tool in psychiatry to individualize
      and optimize the outcomes (efficacy/safety balance) of psychopharmacological drug
      treatment in the individual patient by dose adjustments based upon measured serum
      concentrations. In children and adolescents the administration of psychotropic
      drugs is a general indication for performing TDM. However, TDM studies specific
      in these age groups are necessary to identify age and indication specific
      therapeutic ranges of serum concentrations. Systematic collection of data on drug
      exposure, serum concentrations and clinical characteristics as well as outcomes
      can generate such practice-based evidence. A German-Swiss-Austrian competence
      network for TDM in child and adolescent psychiatry using a multi-centre internet
      based data infrastructure was founded to document and collect demographic, safety
      and efficacy data as well as blood concentrations of psychotropic drugs in
      children and adolescents (further information: www.tdm-kjp.com).

PMID- 21959787
TI  - Therapeutic drug monitoring in pharmacovigilance and pharmacotherapy safety.
AB  - Quantification of serum or plasma concentrations of medications is essential to
      find out if an adverse drug effect (ADE) is associated with an elevated drug
      concentration. In former years TDM was therefore often used in pharmacovigilance
      just to confirm that an ADE that had already occurred was due to an elevated drug
      plasma concentration without identifying the underlying cause for the surprising
      high concentration. This old approach of Therapeutic Drug Monitoring (TDM) in
      pharmacovigilance needs to be revised due to new developments in information
      technology, new analytical procedures and due to the inclusion of clinical
      pharmacological expert opinions in the presentation of laboratory medicine
      results. Today, TDM may be used to prevent ADE, rather than just confirming a
      suggested cause of an ADE that has happened in the past. This approach means that
      blood should be drawn for TDM analysis after the pharmacokinetic steady state has
      been reached (5 times of the elimination half life of the drug) with low to
      moderate dosages under the intended (poly)medication if the patient is clinically
      regarded as not belonging to the "normal" patient population. With the
      availability of reliable automated analytical methods this can be performed at a
      reasonable price. Funds may be saved to the health care system, because
      hospitalization will be thereby shortened and expensive diagnoses and treatment
      of ADE will be avoided. However, this has still to be proven in cross-system
      studies: Budget will be saved in 2 areas of the health system (hospital stay and
      drug costs), whereas a much smaller amount of money has to be invested for
      laboratory analyses in another area. TDM may thus change pharmacovigilance as a
      tool for monitoring and documentation of ADE to a safety tool in drug therapy for
      prevention of ADE.

PMID- 21959788
TI  - Therapeutic drug monitoring in Italian psychiatry.
AB  - INTRODUCTION: Therapeutic drug monitoring (TDM) aims to optimize pharmacotherapy
      treatment. Knowledge, availability and use of TDM for psychiatric patients,
      however, differ between countries. In this survey we analysed the practice in
      Italy of TDM for psychoactive drugs. METHODS: A semi-structured questionnaire was
      sent out to 211 mental health centres (centro di salute mentale) and 10
      university hospitals from each region in Italy. RESULTS: Feedback was obtained
      from 44 centres. Information collected by the questionnaires indicated that in
      Italian psychiatry TDM is used for lithium, valproic acid and carbamazepine. With
      regard to clozapine, TDM was regarded as the blood cell counting which is
      obligatory when prescribing this drug. TDM was not employed for antidepressant or
      antipsychotic drug prescribing. Moreover, it appeared that only a few
      laboratories in Italy offer TDM services for psychiatric patients. Nevertheless,
      interest was expressed about receiving further information about TDM in
      psychiatry and participating in training programmes. DISCUSSION: This nationwide
      survey revealed that in Italy, TDM of psychoactive drugs is restricted to only a
      few drugs. In response to interest expressed, mental health workers should be
      educated about TDM and more laboratories should be encouraged to establish TDM
      services for psychotropic drugs.

PMID- 21959789
TI  - Predicting response to psychopharmacological treatment: survey of recent results.
AB  - INTRODUCTION: Treatment with antidepressants and antipsychotics, though
      effective, is unspecific as agents that differ greatly in their biochemical and
      pharmacological actions have virtually the same efficacy. Half of the patients
      with initial improvement show incomplete response, while a large proportion of
      patients exhibit a refractory clinical picture which is resistant to all
      treatment modalities. METHODS: Our analyses were based on a reference study of
      2,848 depressive inpatients under monotherapeutic treatment with 7 different
      antidepressants or placebo, along with a naturalistic study of depressive and
      schizophrenic patients (296 inpatients, 363 outpatients) under today's "standard"
      polypharmaceutic treatment regimens. RESULTS: The empirical data suggested the
      following predictors of response: (1) severity at baseline, (2) early onset of
      improvement, (3) unwanted side-effects, and (4) medical comorbidity. A
      combination of these predictors with Therapeutic Drug Monitoring (TDM) methods
      has direct clinical relevance. DISCUSSION: Evidence-based approaches to
      personalized treatment help improving the unsatisfactory situation patients and
      clinicians are faced with, given today's incomplete treatments and the fact that
      the mechanisms by which antidepressants and antipsychotics ultimately exert their
      therapeutic effects are only marginally understood.

PMID- 21959790
TI  - Calf implants: a 25-year experience and an anatomical review.
AB  - BACKGROUND: Body contouring in the calf region is becoming a more frequently
      requested procedure. There are several techniques for calf enhancement, including
      implants, liposuction, and free flaps. Alloplastic augmentation can be performed
      with several implant types and several layers of pocket dissection. We present
      our 25 years of experience using the subfascial technique for calf implantation
      along with an anatomical study to illustrate all the important steps and relevant
      anatomy of this augmentation technique. METHODS: The subfascial technique was
      performed in 25 cadavers, in which the important layers were dissected for high
      resolution photos of the surgery to learn about the relevant anatomy of the
      region. Also, we did a retrospective study of our experience with calf implants,
      studying the aesthetic outcome, the presence of early complications, and the
      presence of late complications. RESULTS: We performed dissections in 25 cadavers
      and surgery in 63 patients (126 implants). In our series of patients the final
      aesthetic index was of 9.8. The early complications were severe postoperative
      pain (11.11%), infection (0.79%), seroma (21.42%), hematoma (0%), and wound
      dehiscence (7.14%). The late complications were capsular contracture (Baker
      grades III and IV) (3.17%), implant rupture (1.58%), implant leaking (0%),
      implant displacement (3.96%), numbness at the ankle (2.38%), and palpability of
      the implant (0%). CONCLUSION: The subfascial technique for calf augmentation has
      complication rates low enough and surgical outcomes good enough to recommend it
      as the gold standard for alloplastic calf augmentation.

PMID- 21959792
TI  - A novel targeted multi-functional fusion protein possesses inhibitory activities
      against bacteria, thrombin and platelet aggregation.
AB  - In the present study, we designed a novel targeted multi-functional fusion
      protein LHAD composed of LL-37, FXa recognition peptide, hirudin-12-residue, AAP,
      and RGD peptide. It was expressed in the Pichia pastoris GS115 strain and
      purified by affinity chromatography. The in vitro studies suggested that the
      novel designed protein exhibited antibacterial activity, anti-platelet
      aggregation and anti-thrombin activities. Moreover, the capability of anti
      thrombin was significantly increased compared to that of natural hirudin. Our
      study may provide a potential approach to design multi-functional drugs for the
      prevention and management of thrombosis.

PMID- 21959793
TI  - Biochemical and enzymatic study of rice BADH wild-type and mutants: an insight
      into fragrance in rice.
AB  - Betaine aldehyde dehydrogenase 2 (BADH2) is believed to be involved in the
      accumulation of 2-acetyl-1-pyrroline (2AP), one of the major aromatic compounds
      in fragrant rice. The enzyme can oxidize omega-aminoaldehydes to the
      corresponding omega-amino acids. This study was carried out to investigate the
      function of wild-type BADHs and four BADH2 mutants: BADH2_Y420, containing a Y420
      insertion similar to BADH2.8 in Myanmar fragrance rice, BADH2_C294A, BADH2_E260A
      and BADH2_N162A, consisting of a single catalytic-residue mutation. Our results
      showed that the BADH2_Y420 mutant exhibited less catalytic efficiency towards
      gamma-aminobutyraldehyde but greater efficiency towards betaine aldehyde than
      wild-type. We hypothesized that this point mutation may account for the
      accumulation of gamma-aminobutyraldehyde/Delta(1)-pyrroline prior to conversion
      to 2AP, generating fragrance in Myanmar rice. In addition, the three catalytic
      residue mutants confirmed that residues C294, E260 and N162 were involved in the
      catalytic activity of BADH2 similar to those of other BADHs.

PMID- 21959794
TI  - Micrometer-sized, nanoporous, high-volumetric-capacity LiMn0.85Fe0.15PO4 cathode
      material for rechargeable lithium-ion batteries.

PMID- 21959795
TI  - Gefitinib resistance in HCC mahlavu cells: upregulation of CD133 expression,
      activation of IGF-1R signaling pathway, and enhancement of IGF-1R nuclear
      translocation.
AB  - Hepatocellular carcinoma (HCC) is the major form of primary liver cancer which
      accounts for more than half million deaths annually worldwide. While the
      incidence of HCC is still on the rise, options of treatment are limited and the
      overall survival rate is poor. The acquisition of cancer drug resistance remains
      one of the key hurdles to successful treatment. Clearly, a thorough understanding
      of the underlying mechanisms is needed for new strategies to design novel
      treatments and/or to improve the current therapies. In the present study, we
      examined the expression of cancer stem cell (CSC) marker CD133, the activation of
      insulin-like growth factor 1 receptor (IGF-1R) signaling, and the nuclear
      translocation of IGF-1R in HCC Mahlavu cells under the treatment of gefitinib, a
      cancer drug that inhibits epidermal growth factor receptor (EGFR) pathway. Our
      results demonstrated that Mahlavu cells exhibited strong gefitinib resistance and
      the CD133 expression level was dramatically increased (from 3.88% to 32%) after
      drug treatment. In addition, the gefitinib treated cells displayed increased
      levels of phosphorylation in IGF-1R and Akt, indicating the intensified
      activation of this cancer-associated signaling pathway. Moreover, we revealed
      that IGF-1R underwent nuclear translocation in gefitinib treated cells using
      confocal microscopy. The IGF-1R nuclear translocation was enhanced under
      gefitinib treatment and appeared in a dose-dependent manner. Our findings suggest
      that increased IGF-1R nuclear translocation after gefitinib treatment may
      contribute to the drug resistance and IGF1-R activation, which might also
      associate with the upregulation of CD133 expression.

PMID- 21959796
TI  - Subsequent injury definition, classification, and consequence.
AB  - OBJECTIVE: To examine if different definitions of "recurrent injury" affect the
      distribution of subsequent injury types and their consequences. DESIGN: Secondary
      analysis of prospective injury data. SETTING: Circus shows. PARTICIPANTS: Circus
      artists (n = 1281). MAIN OUTCOME MEASURES: A subsequent injury after an index
      injury was categorized as (1) new injury: different location; (2) local injury:
      same location, different type; and (3) recurrent injury: same location/type.
      Subsequent injuries were stratified according to when they occurred after the
      index injury: early (<=90 performances), late (91-540 performances), and delayed
      (>540 performances). "Healed injury" was either date of return to full
      participation (RTP) or last treatment. RESULTS: Eight hundred twenty-one artists
      (64%) incurred 2 medical attention injuries, and 296 artists (23%) incurred 2
      time loss injuries. In both medical attention and time loss injuries, recurrent
      (range, 7.5%-8.3%) and local injuries (range, 4%-7%) occurred less frequently
      than subsequent new injuries (range, 81%-87%). Time loss injuries recurred later
      than medical attention injuries. The pattern of early, late, and delayed injuries
      was similar for new, local, and recurrent injuries. A greater number of "early"
      injuries are seen with the treatment definition compared with RTP. Subsequent
      injuries had similar number of treatments and missed performances (consequences)
      as index injuries. CONCLUSIONS: In our data, there were a greater number of local
      and recurrent time loss injuries compared with medical attention injuries, but
      the injury definition did not affect the relative number of early, late, or
      delayed injuries. Recurrent injuries are an important component of injury
      prevention, and clear definitions when presenting recurrent injury data are
      necessary.

PMID- 21959797
TI  - Attitudes and beliefs of sports medicine providers to sickle cell trait screening
      of student athletes.
AB  - OBJECTIVE: To describe the attitudes of members of the American Medical Society
      for Sports Medicine (AMSSM) toward the new National Collegiate Athletic
      Association (NCAA) policy to require all Division I student athletes be screened
      for sickle cell trait (SCT), have prior evidence of testing, or sign a waiver.
      DESIGN: Cross-sectional survey of members of the AMSSM electronic mailing list
      was conducted. Descriptive, McNemar, and chi2 statistics were performed. SETTING:
      Internet survey. PARTICIPANTS: Of the 1765 AMSSM e-mail list members, 370
      returned partial or completed surveys. MAIN OUTCOME MEASURES: Dependent variables
      included familiarity with the NCAA policy, support of universal or targeted
      screening programs, preferences regarding screening methodologies, and athletic
      restrictions or modifications for student athletes identified with SCT.
      Respondents' gender, race/ethnicity, and involvement as an NCAA team physician
      were independent variables. RESULTS: Of the respondents, 76% were men, 85% were
      whites, and 53% served as NCAA Division I team physicians. Ninety percent were
      aware of the policy. There was greater support for targeted (76%, 267 of 353)
      compared with universal (39%, 137 of 353; P < 0.01) screening, with targeting
      based on race/ethnicity and sport. Respondents supported targeted screening of
      varsity and freshman athletes in all NCAA divisions, but most (88%) also
      supported waivers. Respondents favored using existing medical records (73%) or
      Sickledex screening (71%) methodologies despite concerns about inaccuracies (16%
      for each methodology). Most respondents agreed that there is discrimination in
      athletic participation and obtaining insurance. CONCLUSIONS: There is lack of
      consensus within the AMSSM regarding the current NCAA SCT screening policy.
      Implementation must take into consideration potential discrimination.

PMID- 21959798
TI  - Survey of injuries in Seattle area levels 4 to 10 female club gymnasts.
AB  - OBJECTIVE: To evaluate incidence, distribution, and contributing factors of
      injury in club gymnastics. DESIGN: Cross-sectional survey. SETTING: Five randomly
      selected gymnastics clubs near Seattle, WA. PARTICIPANTS: Ninety-six club
      gymnasts from competitive levels 4 to 10. INTERVENTIONS: The participants
      completed a questionnaire regarding demographics, injuries and contributing
      factors, and exposure time in the last competitive season. MAIN OUTCOME MEASURES:
      Acute and overuse injury incidence rates stratified by practice and competition,
      age categories, and level using relative risks and 95% confidence intervals
      (CIs). Chi-square testing was used to compare demographic-specific and gymnastic
      specific variables between injured and uninjured. Multivariate regression
      modeling was used to assess independent risk factors for risk of acute and
      overuse injuries. RESULTS: Acute injury rate was 1.3 per 1000 hours and in
      univariate, but not multivariate analysis, it was 3.6-fold greater (95% CI, 1.6
      9.1) among 10 to 12 year olds and 3.1-fold greater (95% CI, 1.3-8.0) among 13 to
      17 year olds compared with 7 to 9 year olds. The most common acutely injured body
      parts were foot (21.0%), ankle (19.3%), knee (14.0%), and wrist (8.8%). The
      majority of injuries occurred in practice, but the meet injury rate was higher.
      Most injuries occurred on floor exercise (32.1%), beam (20.7%), and bars (17.0).
      Injury was most common during landing. The overuse injury rate was 1.8 per 1000
      hours. During their gymnastics careers, concussions occurred in 30.2% and stress
      fractures affecting mostly low back and foot occurred in 16.7% of the gymnasts.
      CONCLUSIONS: Gymnasts are at similar risk of acute and overuse injuries, and
      acute injury rates were greater among older gymnasts. However, this predictor did
      not remain significant in multivariate analysis. Concussions and stress fractures
      are common. Gymnastics injury prevention studies should focus on older gymnasts,
      concussion education, and landing after a skill.

PMID- 21959799
TI  - Preparation of cross-linked carboxymethyl jackfruit starch and evaluation as a
      tablet disintegrant.
AB  - The main purposes of this study are to prepare cross-linked carboxymethyl
      jackfruit starch (CL-CMJF) and to evaluate its pharmaceutical property as a
      tablet disintegrant. CL-CMJF was prepared by a dual carboxymethyl-crosslinking
      reaction in a flask containing jackfruit seed starch (JFS), chloroacetic acid
      (CAA), sodium hydroxide (NaOH) and sodium trimetaphosphate (STMP). The reaction
      was carried out using methanol as a solvent for 60 min at 70 degrees C and at
      JFS:CAA:NaOH:STMP ratio of 1.0:0.29:0.28:0.07. The obtained CL-CMJF, with degree
      of substitution and degree of crosslinking calculated to be 0.34 and 0.06,
      respectively, was insoluble but swellable in water. Rheological study revealed a
      decreased in solution viscosity compared to the non-crosslinked CMJF. The water
      uptake of CL-CMJF was 23 times higher than that of native starch and was
      comparable to that of a commercial superdisintegrant, sodium starch glycolate
      (SSG). The swelling ability of CL-CMRS was similar to that of crosscarmellose
      sodium (CCS), another commercial superdisintegrant. Disintegration test of
      aspirin tablets containing 2%w/w of JFS, CL-CMJF, SSG and CCS showed
      disintegration times in the order of SSG < CCS ~ CL-CMJF <<< JFS. The results
      suggested that CL-CMJF could be developed as a tablet disintegrant.

PMID- 21959800
TI  - Bioequivalence evaluation of norfloxacin tablets based on in vitro - in vivo
      correlation.
AB  - Present study was designed to establish in-vitro and in-vivo correlation (IVIVC)
      of two immediate release tablet formulations of 400mg Norfloxacin [Drug A as test
      and Drug B as reference]. Dissolution study was conducted in 0.1 N HCl using USP
      apparatus II. In-vivo evaluation was carried out in 18 healthy humans according
      to a single dose, two-sequence, and cross-over randomized with a wash-out period
      of one week. After dosing, serial blood samples were collected for a period of 10
      hours. Plasma harvested from blood, was analyzed for norfloxacin by a sensitive,
      reproducible and accurate HPLC method. Various pharmacokinetic parameters were
      determined from plasma concentrations for both the formulations. Non-significant
      difference was found for test/reference ratio of these parameters and the value
      of F was found to be 0.99 which is in good agreement with the limits given in FDA
      and WHO guidelines for such parameters. Difference factor (f(1)), similarity
      factor (f(2)) and level A IVIVC were evaluated showing that drug A is
      bioequivalent to drug B.

PMID- 21959801
TI  - Effects of marmin, a compound isolated from Aegle marmelos Correa, on contraction
      of the guinea pig-isolated trachea.
AB  - Marmin or 7-(6',7'-dihydroxygeranyl-oxy)coumarin is a compound isolated from
      Aegle marmelos Correa. In the study, we examined the effects of marmin on the
      contraction of guinea pig-isolated trachea stimulated by several inducers, namely
      histamine, metacholine, compound 48/80. We also evaluated its action against
      contraction induced by extracellular or intracellular calcium ion. The
      possibility of marmin to potentiate the relaxation effect of isoprenaline was
      also studied. Marmin added in the organ bath at 10 min prior to the agonist
      inhibited the contraction elicited by histamine and metacholine in a
      concentration-dependent manner. Moreover, marmin antagonized the histamine
      induced contraction in competitive manner. Marmin mildly potentiated the
      relaxation effect of isoprenaline. In the study, marmin abrogated the contraction
      of tracheal smooth muscle induced by compound 48/80, an inducer of histamine
      release. Besides, marmin successfully inhibited CaCl(2)-induced contraction in
      Ca(2+)-free Krebs solution. Marmin also inhibited two phases of contraction which
      were consecutively induced by metacholine and CaCl(2) in Ca(2+)-free Krebs
      solution. Based on the results we concluded that marmin could inhibit contraction
      of the guinea-pig tracheal smooth muscle, especially by interfering histamine
      receptor, inhibiting the histamine release from mast, inhibiting intracellular
      Ca(2+) release from the intracellular store and the Ca(2+) influx through voltage
      dependent Ca(2+) channels.

PMID- 21959802
TI  - Preparation and in-vitro in-vivo evaluation of sustained release matrix
      diclofenac sodium tablets using PVP-K90 and natural gums.
AB  - Conventional dosage form is nowadays mostly replaced by sustained release
      formulation in order to increase drug efficacy and patient compliance. The
      sustained release properties of the PVP K90 alone and in combination with guar
      gum, xanthan gum and gum tragacanth were evaluated using diclofenac sodium (100
      mg/tablet) as a model drug. Tablets were processed using wet granulation method
      and evaluated for sustained drug release properties. The drug release from the
      formulations was studied in relationship with Commercially available Diclofenac
      Sodium SR, used as a reference tablets and results were expressed as similarity
      (f1) and differential factor (f2). The tablets prepared using PVP K90 160
      mg/tablet sustained the release of diclofenac sodium for 12 hours. Formulations
      where the PVP K90 was partially replaced with different gums also sustained the
      release of drug for 12 hours. The release of the drug from these formulations
      mainly followed Higuchi model and super case-II and Non-Fickian diffusion.  The
      in-vivo drug release was studied in healthy human volunteers using non-blinded
      cross over, two period design using Diclofenac Sodium SR Tablets as a reference
      drug. The relative bioavailability of the formulation containing PVP K90 and gum
      tragacanth was 0.91. The studies showed that the use of the PVP K90 in
      combination with gum tragacanth both in-vitro and in-vivo sustained the release
      of the drug.

PMID- 21959803
TI  - Contraceptive, estrogenic and anti-estrogenic potentials of methanolic root
      extract of Carpolobia lutea in rodents.
AB  - Several plants are used in herbal medicine for family planning. Carpolobia lutea
      is a medicinal plant in South Eastern Nigeria used for family planning. The study
      was designed to investigate the contraceptive, estrogenic and antiestrogenic
      potentials of the methanolic root extract of Carpolobia lutea in both rats and
      mice. The contraceptive effect of extract (7 - 21mg/kg) administered by
      intraperitoneal route for four days in divided doses was tested in mice and rats.
      Sexually-active males were introduced on day 5 at the ratio of 3F:1M and kept
      with these females till the end of the experiment. Investigations on the
      estrogenic and antiestrogenic property of the extract (7-21mg/kg) were done in
      immature rats that had undergone surgical removal of both ovaries. The effects of
      the extract (vaginal opening, vaginal cornification, uterine wet weight) were
      compared with 17-beta-estradiol (0.1ug/rat/day) as standard drug. Twenty-four
      hours later, the animals were sacrificed following the last dose and the weights
      of uterus, kidney, liver and small intestine were recorded. The extract prevented
      conception in both mice and rats for two gestational periods. Significant changes
      (p<0.05-0.001) were observed in the length and weight of pups relative to
      control. There were no abnormalities observed in the pups over thirty days. In
      ovariectomized immature young rats, the extract showed estrogenic effect (vaginal
      opening, vaginal cornification and increased uterine wet weight) in low doses
      while in high doses, it showed anti-estrogenic effect. These findings agree with
      the traditional use of Carpolobia lutea in the control of fertility. The
      contraceptive property of the extract may be associated with the direct effects
      of its chemical constituents.

PMID- 21959804
TI  - Preparation and evaluation of 5, 9-dimethyl-2-cyclopropyl-2-decanol as a
      penetration enhancer for drugs through rat skin.
AB  - In the present study a new alcohol derivative of tetrahydrogeraniol (THG), an
      acyclic monoterpene, has been prepared by using Grignard reagent and methyl
      cyclopropyl ketone. Penetration enhancing effects of THG and the synthesized
      derivative 5,9-dimethyl-2-cyclopropyl-2-decanol (DICNOL) on the transdermal
      penetration of 5-fluorouracil (5-FU) and tramadol hydrochloride (tramadol HCl)
      across the excised rat skin were studied by an in vitro permeation technique
      using Franz diffusion cells. Azone was used as standard enhancer for comparison.
      DICNOL and THG significantly enhanced 5-FU and tramadol HCl penetration through
      rat skin compared with the control. DICNOL enhanced the permeability of 5-FU and
      tramadol HCl across full thickness skin by about 11 and 20 fold, respectively.
      Increased partition coefficient and diffusion coefficient values were obtained by
      these enhancers. The results suggest that the amount of DICNOL in the skin,
      especially in the stratum corneum, may be related to its penetration enhancing
      effects.

PMID- 21959805
TI  - Effect of binary and ternary solid dispersions on the in vitro dissolution and in
      situ rabbit intestinal absorption of gliclazide.
AB  - Solid dispersion technique is widely used to improve the dissolution rate of
      drugs. Most investigators relied on the in-vitro characterization and considered
      the enhanced dissolution as an indication of improved bioavailability. The
      current study investigated the effects of binary and ternary solid dispersions of
      gliclazide with polyethylene glycol 6000 (PEG 6000) and/or pluronic F68 (PL F68)
      on the dissolution of gliclazide. The study also investigated the intestinal
      absorption in presence of solid dispersion components. The latter employed the in
      situ rabbit intestinal perfusion technique. Preparation of binary solid
      dispersion with PEG 6000 or PL F68 significantly enhanced the dissolution rate
      compared to pure drug. The ternary solid dispersion of gliclazide with both
      polymers resulted in rapid drug dissolution with most drug being released in the
      first five minutes. The intestinal perfusion indicated the possibility of
      complete drug absorption from the small intestine. This, together with slow
      dissolution of pure drug suggested that the absorption of gliclazide is
      dissolution rate limited. The presence of PEG 6000 did not alter the intestinal
      absorption but PL F68 showed a trend of enhanced intestinal absorption of the
      drug. Ternary solid dispersion can thus provide rapid absorption due to rapid
      dissolution and potential increase in intestinal permeability.

PMID- 21959806
TI  - Prevention of CCl(4)-induced oxidative damage in adrenal gland by Digera muricata
      extract in rat.
AB  - Digera muricata (L.) Mart. is a weed and commonly found in waste places, road
      sides and in maize fields during the summer season. It possesses antioxidant
      capacity and is locally used for various disorders such as inflammation,
      urination, as refrigerant, aperient and in sexual anomalies. In this study
      antioxidant potential of Digera muricata methanol extract (DMME) and n-hexane
      extract (DMHE) was evaluated against CCl(4)-induced oxidative stress in adrenal
      gland of Sprague-Dawley male rats. 42 rats were equally divided into 7 groups of
      6 rats in each. Group I remained untreated, while Group II treated with vehicles.
      Group III received only CCl(4) (1 ml/kg b.w., 10% in olive oil) once a week for
      16 weeks. Group IV and VI received DMME and DMHE at a dose of 200 mg/kg b.w.
      along with CCl(4). Animals of Group V and VII administered with DMME and DMHE
      alone at a dose of 200 mg/kg b.w. once a week for 16 weeks. Lipid peroxidation
      significantly increased while activities of antioxidant enzymes (CAT, SOD, GST,
      GSR and GSH-Px) were reduced in adrenal gland samples by the administration of
      CCl(4). Glutathione (GSH) concentration was significantly decreased whereas DNA
      fragmentation% and AgNORs count was increased in adrenal gland by CCl(4)
      administration. Treatment of rat by both the extracts (DMME, DMHE) and CCl(4)
      increased the glutathione level and activities of antioxidant enzymes while
      reduced the lipid peroxidation, DNA fragmentation percent and AgNORs count in
      adrenal gland. These results indicate that Digera muricata extract is able to
      ameliorate oxidative stress in adrenal gland induced by CCl(4) in rat.

PMID- 21959807
TI  - Cytotoxicity of isolated compounds from the extracts of Struchium sparganophora
      (Linn) Ktze asteraceae.
AB  - Chemical investigation of the leaves of Struchium sparganophora by the
      application of VLC, CL and PTLC resulted in isolation of three compounds. The
      cytotoxicity activity of these compounds on malignant human cultured cells was
      examined. Vernodalin showed a significant cytotoxic activity on the melanoma and
      ovarian cancer cell lines (P<0.05) while the conjugated 3 methyl, 2, 6
      hexacosedienol and luteolin caused cell death after 48h reculture without them.
      These compounds portend an effective remedy if subjected to structural
      modification to enhance its' efficacy and the dietary importance of this plant as
      a culinary herb in west Africa countries is evidence by the presence of these
      antitumour compounds in this plant.

PMID- 21959808
TI  - A comparative study of antioxidant vitamins and simvastatin in
      hypercholesterolimic rabbits.
AB  - The anti-lipidemic effects of orally administered antioxidant vitamins (vitamin
      A, vitamin C and vitamin E) individually and in combination were studied in
      cholesterol-fed rabbits and compared to the group of hypercholesterolemic animals
      that were treated with simvastatin. All treatment groups exhibited a decrease in
      serum total cholesterol, low density lipoprotein-cholesterol (LDL-C) and
      triglycerides concentrations, whilst vitamin C, vitamin E, the combination and
      simvastatin showed a more profound decrease in the lipid profile than vitamin A
      at different time intervals. The order of increase in high density lipoprotein
      cholesterol (HDL-C) levels remained in favour of simvastatin, as none of the
      antioxidant vitamins treated group could exhibit a profound increase in the HDL
      C.

PMID- 21959809
TI  - Anti-hyperglycemic and antinociceptive activity of methanol leaf and stem extract
      of Nypa fruticans Wurmb.
AB  - Nypa fruticans Wurmb. (Arecaceae) is a mangrove palm well-known for its
      traditional uses by the local practitioners against different ailments in
      southern regions of Bangladesh. However, the plant is yet to be scientifically
      studied. The present study was done to evaluate the anti-hyperglycemic and
      antinociceptive potential of methanolic extract of leaf and stem of Nypa
      fruticans Wurmb. (MENF). The anti-hyperglycemic activity was tested on glucose
      loaded hyperglycemic mice whereas antinociceptive activity was evaluated using a
      model of acetic acid-induced writhing in mice. The crude MENF was found to show
      significant oral anti-hyperglycemic activity on glucose loaded mice at every
      dose. Maximum anti-hyperglycemic activity was observed at a dose of 500 mg
      MENF/kg body weight, which was more than what was obtained with a standard drug
      glibenclamide at a dose of 10 mg glibenclamide/kg body weight). Significant
      antinociceptive activity was also demonstrated by MENF in acetic acid-induced
      writhing mice model. The extract caused a maximum of 39.88% (p<0.001) inhibition
      of writhing at the dose of 600 mg/kg body weight, which was better than the
      result obtained with a standard drug (200 mg aspirin/kg body weight, 49.34%
      inhibition). These findings indicate that MENF has significant anti-hyperglycemic
      and antinociceptive activity and thus have great potential as a source of natural
      products.

PMID- 21959810
TI  - The antifungal, cytotoxic, antitermite and insecticidal activities of Zizyphus
      jujube.
AB  - Plants are very useful, self-generating machines, producing a variety of useful
      bioactive products. Keeping in view this idea, the crude methanolic extract and
      various fractions of Zizyphus jujuba were screened for antifungal, cytotoxic,
      antitermite and insecticidal activities. Low activity was shown by the crude
      methanolic extract (12%), n-hexane (9%), chloroform (20%) and ethyl acetate (14%)
      fraction against Penicillium notatum. Low activity was shown by the n-hexane
      fraction against Aspergillus niger (10%) and Trichoderma harzianum (13%) and
      inactive against Aspergillus flavus, Fusarium oxysporum and Rhizopus stolonifer.
      The CHCl(3) fraction exhibited low activity of 10% against F. oxysporum while
      showing no activity against the rest of the test fungi. All the test samples were
      inactive against Rhizopus stolonifer. The crude methanolic extract was highly
      cytotoxic (73.33%) at the concentration of 1000 (ug/ml) while the rest of the
      test samples were low in toxicity at the same concentration. The crude methanolic
      extract of Zizyphus jujuba showed significant antitermite activity against
      Heterotermes indicola, among the test samples. Against Tribolium castaneum,
      Rhizopertha dominica and Callosbruchus analis the insecticidal activity was
      determined. All the test samples except n-hexane showed low activity (20%)
      against T. castaneum. The n-hexane fraction showed low activity (20%) against R.
      dominica while the rest of the fractions were inactive against it. Low activity
      of 40% and 20% was shown by the chloroform and n-hexane fraction respectively
      against C. analis. The results of the present study revealed that the plant could
      be as potent source of cytotoxic drugs.

PMID- 21959811
TI  - Aceclofenac delivery by microencapsulation using LBL self-assembly for delayed
      release.
AB  - Colonic targeting has gained increasing interest over the past years, not just
      for the transport of drugs for the treatment of local diseases associated with
      the colon but also for its potential for transporting peptides and proteins,
      particularly low molecular weight peptide drugs. Without protection, such peptide
      drugs are usually digested within the gastric and small intestinal sections. In
      the present work Layer-By-Layer (LBL) self-assembly was utilized to make
      Aceclofenac single bilayer microcapsules produced by sequential adsorption of
      positively charged chitosan and negatively charged Pectin on the external surface
      of negatively charged Aceclofenac microcrystals. Taguchi approach was applied to
      determine the best concurrence of composition factors that is concentration of
      chitosan, pectin, centrifugation speed and incubation time. The microcapsules
      were characterized for encapsulation efficiency, particle size, zeta potential,
      scanning electron microscopy and in-vitro release kinetics. Surface electric
      potential of Aceclofenac microcrystals was found to be negative with zeta
      potential -1.39 mV, in acetate buffer of pH 4. The primary and the secondary
      deposit layer of chitosan and pectin was found to have a positive and negative
      charge with zeta potential of +5.57 mV and -22.8 mV respectively. The sequential
      changing of surface zeta potential after each deposition is a satisfactory
      indication of the LBL self-assembly of the oppositely charged polyelectrolytes.
      The average size and encapsulation efficiency of the optimized single bilayer
      microcapsules (F5) was found to be 20um and 63.83%, respectively. The ex-vivo
      percentage cumulative drug release of (F5) in Phosphate buffer pH 6.8 containing
      2-4% w/v colonic fecal matter of male albino rat was found to be 98.40%. The
      optimized batch of microcapsules showed first order release kinetics (R(2)=
      0.950) in presence of colonic fecal matter.

PMID- 21959812
TI  - Preparation, characterization and release of verapamil hydrochloride from
      polycaprolactone/acrylic acid (PCL/AA) hydrogels.
AB  - In this study pH sensitive, biocompatible and controlled released hydrogels were
      prepared and their localized drug delivery effect was analyzed. Polycaprolactone
      and acrylic acid (PCL/AA) were reacted by free radical polymerization and
      developed inter penetrating polymeric network (IPN) hydrogels. Benzylperoxide was
      used as initiator and N, N methylenebisacrylamide [NNMBisAm] was employed as a
      cross-linking agent. Different concentrations of monomer, polymer and cross
      linking agent were used and the reaction parameters were optimized. The obtained
      PCL/AA hydrogels were fully characterized by Fourier transform infrared
      spectroscopy (FT-IR), scanning electron microscopy (SEM), and thermogravimetric
      analysis (TGA) that determined the polymer structure, its morphology and strength
      respectively. Verapamil, a calcium channel blocker was loaded by incubation of
      polymerization method. Controlled release Verapamil hydrogel was developed due to
      its low solubility; low permeability and having very short half life of 1.2-2 h.
      The dynamic swelling, equilibrium swelling and drug release were carried out in a
      buffer solution of pH 1.2, 4.5 and 6.8. Concentration of Acrylic acid showed
      direct, while Polycaprolactone inverse relation to swelling and drug release due
      to their hydrophilic and hydrophobic nature respectively. Cross-linking agent
      also had the contrary effect on swelling. Diffusion coefficient (D) of hydrogels
      was determined by using Flory-Rehner theory. Drug release and swelling data were
      analyzed by different kinetic models, like Zero order, First order, Higuchi,
      Korsmeyer's and Peppas. The release and diffusion was best described by the first
      order kinetics where n value was <0.5 for all the formulations indicating Fickian
      drug release mechanism.

PMID- 21959813
TI  - The efficacy of a single dose of pethidine, fentanyl and morphine in treating
      postanesthesia shivering.
AB  - Postanesthesia shivering is an undesirable event that may induce a variety of
      adverse consequences including patient discomfort, increased oxygen consumption
      and wound pain. Thus, its pharmacological treatment should be regarded. The
      purpose of this study was to compare the efficacy of morphine, fentanyl and
      pethidine for the treatment of postanesthesia shivering. Fifty patients who
      developed shivering were treated in a randomized double blinded manner with an
      intravenous bolus dose of 2 or 4 mg morphine, 25 or 50 mg pethidine, and 50 MUg
      fentanyl. Then, they were monitored for 30 minutes and the shivering suppression
      grade, the time taken to stop shivering, the shivering cessation time, recurrence
      of shivering and opioid side effects were evaluated. Core body temperature was
      measured immediately before, and at 15 and 30 minute after administering the
      drug. The groups did not differ significantly regarding shivering suppression
      grade, shivering cessation time, and recurrence of shivering. There was a
      significant difference in the time taken to stop shivering between groups.
      Following injection of the drugs, the core temperatures increased in the five
      groups with statistical difference. All opioids were effective in treating
      postanesthesia shivering in a similar extent.

PMID- 21959814
TI  - In vitro screening of Circium arvense for potential antibacterial and antifungal
      activities.
AB  - The antimicrobial activities of Circium arvense extracts were evaluated against
      two human gram positive (Staphylococcus aureus, Micrococcus luteus) and four gram
      negative pathogen (Escherichia coli, pseudomonas aeruginosa, Enterobacter,
      Klebsiella pneumoniae). The Methanol extracts of Circium arvense were used to
      obtain various fractions (X1) n-hexane, (X2) chloroform, (X3) ethyl acetate and
      (X4) n-butanol. The agar well diffusion assay and agar dilution susceptibility
      testing were carried out to determine the zone of inhibitions and the minimum
      inhibitory concentration respectively. Antifungal activity was employed by agar
      well diffusion method. The Ampicilline, Ofloxacine and Itraconazole were used as
      standard agents. Almost all fractions exhibited more or less antimicrobial
      activity. The X2 (Chloroform) fraction was reported as highly active fraction
      with good antimicrobial activity MIC 0.312 mg/ml against staphylococcus areous.
      The MBC values of fraction X2 (chloroform) was 2 times the MIC. Similarly all
      fractions exhibited good inhibitory activities against Aspergillus niger. The
      fraction X1(n-hexane) was found highly active 6(+/-0.11), followed by X2
      (chloroform) fraction 5 (+/-0.17). Present study provides a base to explore the
      antimicrobial potential of Circium arvense. It is concluded that the Circium
      arvense having potential antibacterial and antifungal activities, irrespective of
      fact that the MIC values reported were high. Further investigations are
      recommended to exploit the hidden medicinal value of plant.

PMID- 21959815
TI  - Analysis of some biochemical and haematological parameters for Mucuna pruriens
      (DC) seed powder in male rats.
AB  - The biochemical and haematological effects of the seed powder of Mucuna pruriens
      in male rats were evaluated to establish some biological properties of this
      potential biopesticide currently undergoing investigation. The result showed that
      Mucuna pruriens seed extract produced a significant (p<0.05) increase in white
      blood cell (WBC) count, as well as in bilirubin concentrations, alkaline
      phosphatase (ALP), protein and creatinine levels measured. Alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly
      reduced (P<0.05) in comparison with the experimental control. PCV, Hb, albumin
      level and WBC differential counts gave no significant difference between treated
      and control groups. The results revealed metabolic imbalance in the rats which
      suggests a mild cholestasis effect of the extract.

PMID- 21959816
TI  - Isolation-drug resistance profile and molecular characterization of indigenous
      typical and atypical mycobacteria.
AB  - One hundred and fifty mycobacterial isolates from different pathological Labs. of
      Karachi were collected and screened as acid fast. On the bases of phenotypic and
      biochemical results, it was found that, 58.66% isolates were typical mycobacteria
      while 41.33% belonged to atypical mycobacteria. The individual percentages of
      different mycobacterial species include: M. xenopi 35%, M. thermoresistible 19 %,
      M. terrae complex 6 %, M. marinum 6 %, M. fortuitum 6 %, M. kansasii 25 % and M.
      tuberculosis 58.66 %. The sensitivity of mycobacterial isolates was determined
      against 5 first line, 3 second line and 1 third line anti-tuberculosis drugs. The
      highest number of the isolates (typical and atypical mycobacteria) offered
      resistance against isoniazid and streptomycin. Clarithromycin was found to be the
      drug of choice as regards the drug sensitivity in case of atypical mycobacterial
      isolates. A total of 40 isolates were subjected to PCR based identification and
      differentiation of 16S rRNA gene(s). Accordingly, 37.5% isolates were identified
      as typical mycobacteria while 25% were identified as atypical mycobacteria. These
      findings carry significance because a detailed research based identification (PCR
      and Multiplex PCR based) regarding indigenous mycobacteria has been reported for
      the first time in Pakistan. However, both the approaches (conventional and
      molecular methods) have experimental importance while identifying these
      organisms.

PMID- 21959817
TI  - Development of meloxicam formulations utilizing ternary complexation for
      solubility enhancement.
AB  - Meloxicam (an oxicam derivative), a relatively new cyclo-oxygenase inhibitor, is
      a member of enolic acid group of non-steroidal anti-inflammatory drugs. It is
      generally used in the treatment of rheumatoid arthritis, osteoarthritis and other
      joint pains. Meloxicam is practically insoluble in water (8ug/ml), which directly
      influences the C(max), T(max), as well as the bioavailability of the drug. In the
      present study, an attempt has been made to improve the dissolution of Meloxicam
      by preparation of its solid dispersion using beta-cyclodextrin blended with
      various water soluble polymer carriers i.e., HPMC (methocel IH), methylcellulose
      (400cps), PVP K30, HPMC (K(4)M), HPMC (50cps). It is reported that when small
      amount of water soluble polymer is added to beta-cyclodextrin, its nature of
      solubilization significantly increases due to increase in the apparent complex
      stability constant. Phase solubility studies were carried out to evaluate the
      solubilizing power of beta-cyclodextrin along with various water soluble
      polymers. The solid dispersion was prepared and formulated into tablets and
      suspension, which were evaluated on the basis of various official tests. All the
      studies suggest that formulations of Meloxicam utilizing solid dispersion
      technique significantly enhances solubility (90 ug/ml) of the drug and results in
      superior formulations of the drug by using beta-cyclodextrin blended with 0.12%
      w/w HPMC (Methocel IH). Ternary complexation is a valuable tool for solubility
      enhancement of drugs.

PMID- 21959818
TI  - Development and implication of a capillary electrophoresis methodology for
      ciprofloxacin, paracetamol and diclofenac sodium in pharmaceutical formulations
      and simultaneously in human urine samples.
AB  - This work studies the development of a simple and fairly rapid methodology for
      simultaneous determination/separation of three frequently co-administered drugs;
      ciprofloxacin (CIP), paracetamol (PCT) and diclofenac sodium (DIC) using
      capillary electrophoresis (CE) with UV detection at 260 nm. Separation was
      achieved in only 6.5 min with a simple buffer of sodium tetraborate (50 mM) at pH
      9.0. The Parameters affecting the separation and detection were optimized. The
      calibration curves were linear in the range of 5-500 ug/mL for CIP, 5-250 ug/mL
      for PCT and 1-125 ug/mL for DIC sodium under the optimized conditions. The lower
      limit of detection (LOD) was found to be 1 ug/mL for CIP & PCT and 0.5 ug/mL for
      DIC. The method was successfully used for the analysis of drugs in commercial
      pharmaceutical formulations and simultaneously from patient's urine sample with
      RSD 0.5-2.4%. Results obtained with CE method are compared with standard HPLC
      procedure and were found in good agreement.

PMID- 21959819
TI  - Antioxidant activities of the leaves of Chrysophyllum albidum G.
AB  - Chrysophyllum albidum G. is a tropical plant and commonly found in Nigeria. It
      belongs to the sapotaceae family and used in folklore in the treatment of yellow
      fever, malaria, diarrhea, vaginal and dermatological infections. The study was
      aimed at investigating the antioxidant properties of this plant by employing the
      in vitro and in vivo experimental models. The effect of DPPH free radical
      scavenging activity on the fractions of petroleum ether, ethanol, butanol,
      ethylacetate, and water of C. albidum was determined. The ethyl acetate fraction
      was purified in column chromatography to obtain myricetin rhamnoside.  Structure
      elucidation was done by NMR and mass spectroscopic techniques. Furthermore,
      ethanol extract was administered to five groups of eight rats per group. The
      animals in the normal group were administered with vehicle alone for 7 days. The
      positive control animals were given vehicle on the first four days, and with the
      vehicle and hepatotoxin (CCl(4)) on the fifth, sixth and seventh day. The animals
      in the treatment category were respectively administered with 500, 1000 and 1500
      mg/kg b.w. of extract & distilled water for the first four days, and with
      distilled water, extract and CCl(4) on the last three days. Animals were
      subsequently anaesthetized and blood samples were collected for catalase (CAT),
      malondialdehyde (MDA), reduced gluthathione (GSH) and superoxide dismutase (SOD)
      assays. The petroleum ether fraction showed the least antiradical activity
      (4057.5 +/- 809.6 g/kg) while ethyl ether exhibited the highest activity (414.4
      +/- 92.0 g/kg). Myricetin rhamnoside also exhibited an excellent radical
      scavenging activity (314.1 +/- 60.2) which was comparable to the positive
      control. Result from animal study showed that C. albidum exhibited significant (p
      < 0.05) differences on the activity of CAT, MDA and GSH. The plant could
      therefore be employed as sources of natural antioxidant boosters and for the
      treatment of some oxidative stress disorders in which free radicals are
      implicated.

PMID- 21959820
TI  - Spasmogenic and spasmolytic activities of Onosma griffithii Vatke.
AB  - Methanolic extract of Onosma griffithii and its fractions were evaluated for
      possible effects on rabbits' jejunum preparations. Rabbits of either sex (weight
      1.5-2.0 kg) were used in experiments. Studies were carried out on rabbits'
      jejunum preparations. Crude methanolic extract of Onosma griffithii (Meth.OG) was
      tried in concentrations of 0.01, 0.03, 0.1, 0.3, 1.0, 3.0, 5.0 and 10.0 mg/ml on
      rabbits' jejunum preparations. Meth.OG was also tried on KCl-induced contractions
      to explain its possible mode of actions in the presence and absence of atropine
      (0.03 uM). Fractions of Meth.OG were tried in similar manner. Calcium chloride
      curves were constructed for Meth.OG treated tissues that were compared with
      curves constructed for verapamil in same fashion. Preliminary phytochemical
      screening of the plant was also performed. Meth.OG increased the amplitude of
      spontaneous activity of rabbits' jejunum preparations at concentrations of 0.1,
      0.3 and 1.0 mg/ml. However, spasmolytic effects were  observed at higher
      concentrations 3.0, 5.0 and 10.0 mg/ml. Mean EC(50)  values (mg/ml),
      respectively, in absence and presence of atropine were 7.5 +/- 0.25 (6.9-8.4,
      n=6) and 3.0 +/- 0.17 (2.3-3.5, n=6, p<0.05). Mean EC(50) values, respectively,
      for effects on spontaneous and KCl-induced contractions were 7.5 +/- 0.25 (6.9
      8.4, n=6) and 7.3 +/- 0.35 (6.25-8.2, n=6, p<0.05). n-Hexane, chloroform and
      ethyl acetate fractions showed their respective EC(50) values (mg/ml)  9.7 +/-
      0.25 (8.6-10.2, n=6), 4.0 +/- 0.2 (3.5-4.6, n=6) and 1.07 +/- 0.093 (0.78-1.5,
      n=6). EC(50) values for calcium chloride curves in presence of 0.3 mg/ml Meth.OG
      were - 2.27 +/- 0.038 (- 2.4 to - 2.10, n=6) vs. control - 2.78 +/-0.04 (-2.9 to 
      2.6, n=6, p<0.05) Log [Ca(++)]M. Comparing with curves of calcium chloride
      constructed in presence of 0.1 uM verapamil, the EC(50) (log [Ca(++)] M) values
      were - 1.82 +/- 0.087 (- 2.0 to - 1.65, n=6) vs. control - 2.64 +/- 0.089 (- 2.9
      to - 2.4, n=6) demonstrated a right shift (p<0.05). Meth.OG tested positive for
      terpenes, saponins, sterols, flavonoids and carbohydrates. We concluded that the
      relaxant effect of Meth.OG is exerted through blocking of calcium channels.
      However, n-butanolic and aqueous fractions produced spasmogenic effects that
      require further work for isolation of pharmacologically active substances.

PMID- 21959821
TI  - Differential inhibitory potencies of alcoholic extract of different parts of
      Dryopteris chrysocoma on inflammation in mice and rats.
AB  - Phytomedicinal therapy for inflammation is not new and it is highly effective for
      the treatment of various inflammatory disorders. The inflammation is one of the
      initial parameter for most of the disorders occurring in the body. The anti
      inflammatory potential can be determined by using various techniques. Dryopteris
      chrysocoma is a male fern commonly found in damp and moist areas of Pakistan. The
      study was conducted on mice and rats by inducing inflammation with subcutaneous
      administration of formalin and Carrageenan in hind paw. The results were compared
      with standard drug Aspirin administered orally in the dose of 300 mg/kg and a
      decrease in hind paw volume was observed. The intensity of edema was observed in
      mice after formalin injection and the time of disappearance of edema was
      observed. In rats the inhibition of inflammation by root, leaves and stem extract
      was 51.19%, 41.66% and 30.95% respectively after administration of formalin.
      Similar inhibition of inflammation produced by root, leaves and stem extracts
      i.e. 57%, 42% and 35% respectively in Carrageenan treated rats. Root extract
      showed the highly significant results at p <= 0.05. The comparative study
      explored the root extract has more potent anti-inflammatory activity than leaves
      extract. The stem extract has less potent anti-inflammatory action.

PMID- 21959822
TI  - Garlic (Allium sativum) supplementation with standard antidiabetic agent provides
      better diabetic control in type 2 diabetes patients.
AB  - Garlic has been used safely since ancient times as both food and medicine in
      human populations, but studies of its efficacy in the management of diabetes have
      yielded conflicting results. This study has evaluated the potential hypoglycemic
      effects of garlic in type 2 diabetic patients. The study was conducted in
      diagnosed type 2 diabetic patients (n=60) with fasting blood sugar level above
      126 mg/dl to evaluate the effects of adding garlic tablets with standard
      antidiabetic therapy on blood sugar. Patients were divided randomly into 2
      groups. Group 1 (n=30) was given tablet Garlic (KWAI) 300 mg thrice daily +
      Metformin 500 mg twice daily and Group 2 (n=30) was given Placebo+Metformin 500
      mg twice daily respectively for 24 weeks. Serum lipids and fasting blood glucose
      were measured at week 0, 12 and week 24.  Group1 showed significant reduction in
      fasting blood sugar at week 24 with a percentage decrease of (-3.12 percent) (P =
      <0.005) as compared to group 2 (0.59 percent). At the end of week 24, GR1 group
      also showed considerable decrease in mean total cholesterol (6.2 mg/dl, -2.82%,
      P=<0.005), LDL-C (-3 mg/dl, 2.18% P=<0.005), triglycerides (-5.2 mg/dl, 3.12%,
      P<0.005) while HDL cholesterol was significantly increased (2.36 mg/dl, 6.72%,
      P<0.005) as compared to GR2 group. Combination of garlic with typical
      antidiabetic remedy has shown to improve glycemic control in addition to
      antihyperlipidemic activity. Garlic may be a good addition in the management of
      patients with diabetes and hyperlipidemia.

PMID- 21959823
TI  - Synthesis, characterization and biological activity of some 1, 3, 4-thiadiazol
      derivatives.
AB  - Thiadiazoles are their derivatives exhibit a wide variety of pharmacological
      activities such as Antibacterial and anti-inflammatory. In the present study we
      have synthesized derivatives some 2,5 substituted 1,3,4- thiadiazoles. The
      structures of these synthesized compounds were confirmed by IR, NMR, and MASS
      spectra data. These compounds were evaluated for varies biological activities
      such as antibacterial and anti-inflammatory activity.

PMID- 21959824
TI  - Fabrication of potential macromolecular prodrugs of aspirin and diclofenac with
      dextran.
AB  - Aspirin and diclofenac conjugates with dextran were synthesized as potential
      macromolecular prodrugs under homogeneous reaction conditions by using 4-methyl
      benzenesulfonyl chloride as an acylating agent in the presence of triethylamine
      as a base. Highly pure conjugates with good yields were synthesized by this
      acylation method. All of the products were found soluble in aqueous medium as
      well as in dimethylsulfoxide and N,N-dimethylacetamide. The UV/Vis
      spectrophotometry has indicated the incorporation of drugs in conjugates and
      extent of substitution of drug onto dextran polymer. Covalent attachment of the
      drug onto the drug carrier polymer (dextran) was verified by (1)H NMR and Fourier
      transform infrared (FTIR) spectroscopic analysis. The prodrugs were analysed by
      powder X-ray diffraction (XRD) measurements. Phase changes were noticed by powder
      XRD for all macromolecular prodrugs indicating the change of state of matter
      towards more crystallinity. Therefore, fabricated macromolecular prodrugs are
      potential candidates to show better pharmacokinetic profile. All of the products
      were thoroughly characterized by using different spectroscopic techniques.

PMID- 21959825
TI  - To study the efficacy of Losartan on urinary uric acid excretion in Thiazide
      induced hyperuricemic and hypertensive patients.
AB  - The precise relationship of Hyperuricemia found in hypertensive patients is still
      obscure; this study is a urinary uric acid lowering intervention with Losartan in
      hypertensive patients induced by Thiazide diuretics. A number of pharmacological
      agents like loop diuretics, similarly low doses of aspirin (<3g daily) aggravate
      Hyperuricemia. The effect of Losartan on urinary uric acid excretion In
      Hypertensive patients with Thiazide induced Hyperuricemia were investigated in
      the Department of pharmacology and therapeutics, Basic Medical Sciences Institute
      Jinnah Postgraduate Medical Centre Karachi. It was randomized, open label,
      prospective, comparative study. Total 60 hypertensive Hyperuricemic patients were
      enrolled one by one in this study, selected from medical OPD and wards of Jinnah
      Postgraduate Medical Centre, Karachi. Patients were divided in three groups.
      Group-1 patients were treated with Thiazide 50 mg/day, Group-2 with Losartan +
      Thiazide 50 mg/day, and Group-3 with Losartan 50 mg/day. The effect on urinary
      uric acid level was measured, after every fortnightly. Treatment with Thiazide +
      Losartan group and Losartan group showed significantly increase in urinary uric
      acid excretion. Whereas, Thiazide group decrease in urinary uric acid level. In
      contrast to Thiazide and Losartan alone Thiazide + Losartan led to a greater
      increased in urinary uric acid excretion. The average percentage increase in
      urinary uric acid excretion  in Thiazide + Losartan group was -13.27% and the
      average percentage increased in urinary uric acid excretion  was 6.7% in Losartan
      group. Thus it can be concluded from the present study that urinary uric acid
      excretion was more increased in combination therapies. Ultimately Losartan
      decrease serum uric acid level and uricosuric effect of Losartan might be
      particularly useful in Hyperuricemic patients those on Thiazide diuretic (for
      hypertension and heart failure).

PMID- 21959826
TI  - Antimalarial activity of three Pakistani medicinal plants.
AB  - This study was conducted to determine the in vitro anti-malarial activity of
      three medicinal plants, Picrorhiza kurroa, Caesalpinia bonducella and Artemisia
      absinthium of Pakistan. Different extracts of various parts of these plants were
      prepared by maceration and percolation, and were evaluated for their antimalarial
      activity. Aqueous, cold alcoholic and hot alcoholic extracts of Picrorhiza kurroa
      showed 34%, 100% and 90% inhibition in growth of Plasmodium falciparum,
      respectively, at 2.00 mg/ml. While aqueous, cold alcoholic and hot alcoholic
      extracts of Caesalpinia bonducella showed 65%, 56% and 76% inhibition in growth
      of Plasmodium falciparum, respectively at same concentrations. In the case of
      Artemisia absinthium, aqueous, cold alcoholic and hot alcoholic extract of
      Artemisia absinthium showed 35%, 55% and 21% inhibition in growth of Plasmodium
      falciparum, respectively at 2.00 mg/ml. In our study, extracts of Picrorhiza
      kurroa were found good for traditional therapy with highly significant results.

PMID- 21959827
TI  - Qadirvirtide.
AB  - Qadirvirtide is a fusion inhibitor that may be used as prophylaxis or for the
      treatment of AIDS. It is a synthetic peptide that is composed of 36 amino acids.
      Qadirvirtide blocks the entry of HIV genome into human CD4 cells by binding to
      HR1 as the virus can not come close to the human cell membrane and ultimately
      fusion of the viral envelope with human cell membrane is prohibited.

PMID- 21959828
TI  - Arterial flow characteristics in the presence of vascular disease and
      implications for fast spin echo-based noncontrast MR angiography.
AB  - PURPOSE: To investigate arterial flow characteristics in the setting of vascular
      disease, and examine their effect on the performance of fast spin-echo (FSE)
      based noncontrast MR angiography (NC-MRA). MATERIALS AND METHODS: Seventeen
      patients were recruited from among those scheduled for routine contrast-enhanced
      MR angiography (CE-MRA) of the lower extremities at 1.5 Tesla. The research
      portion of the exam was performed before the clinically-indicated protocol and
      included phase-contrast imaging at multiple levels in the legs and FSE-based NC
      MRA in the calf and thigh, using a three-dimensional ECG-gated technique that
      exploits differences in arterial flow velocity between diastole and systole.
      RESULTS: Vascular occlusions were associated with reduced systolic velocity, a
      delayed systolic peak, and, in two middle-aged patients, an increase in diastolic
      velocity. Elevated systolic and diastolic velocities were observed in a subject
      with a nonhealing ulcer. NC-MRA allowed visualization of arteries with systolic
      velocities as low as 3 cm/s, and exhibited comparable depiction to CE-MRA for
      diastolic velocities as high as 6 cm/s. At the highest diastolic velocities
      observed (15 cm/s) arterial depiction was severely degraded. CONCLUSION: FSE
      based NC-MRA as presently implemented performs successfully over a wide range of
      flow patterns, but does not accommodate extremely low systolic velocities or very
      high diastolic velocities.

PMID- 21959829
TI  - Usefulness of CT-MRI fusion in radiotherapy planning for localized prostate
      cancer.
AB  - We compared the prostate volumes and rectal doses calculated by CT and CT-MRI
      fusion, and verified the usefulness of CT-MRI fusion in three-dimensional (3D)
      radiotherapy planning for localized prostate cancer. Three observers contoured
      the prostate and rectum of 13 patients with CT and CT-MRI fusion. Prostate
      delineations were classified into three sub-parts, and the volumes and distances
      to the rectum (PR distance) were calculated. 3D radiotherapy plans were
      generated. A dose-volume histogram (DVH) was constructed for the rectum. The
      intermodality and interobserver variations were assessed. CT-MRI fusion yielded a
      significantly lower prostate volume by 31%. In the sub-part analysis, the
      greatest difference was seen for the apical side. The PR distance was
      significantly extended by 3.5-mm, and the greatest difference was seen for the
      basal side. The irradiated rectal volume was reduced in the CT-MRI fusion-based
      plan. The reduction rates were greater in the relatively high-dose regions. The
      decrease of the prostate volume and length alteration of the distance between the
      prostate and rectum were correlated with the decrease of the irradiated rectal
      volume. The prostate volume delineated by CT-MRI fusion was negatively correlated
      with the decrease of the irradiated rectal volume. CT showed a tendency towards
      overestimation of the prostate volume and underestimation of the PR distance as
      compared to CT-MRI fusion. The rectal dose was significantly reduced in CT-MRI
      fusion-based plan. Using CT-MRI fusion, especially in cases with a small
      prostate, the irradiated rectal volume can be reduced, with consequent reduction
      in rectal complications.

PMID- 21959830
TI  - Blood flow change quantification in cervical cancer before and during radiation
      therapy using perfusion CT.
AB  - The purpose of this study was to quantify the changes of tumor blood flow (BF) in
      cervical cancer after radiation therapy by using perfusion computed tomography
      (CT), and to examine the difference between maximum slope (MS) and single-input
      one-compartment model (SOCM) methods. Fourteen consecutive patients who received
      definitive radiation therapy for cervical cancer from October 2009 to February
      2010 were enrolled in this study. Blood flow (BF) analyses were performed using
      both MS and SOCM methods. Quantitative BF maps were created using Body Perfusion
      (Toshiba Medical Systems, Co. Tokyo, Japan). Perfusion color maps were
      successfully created by the two analytical methods. BF of the tumors was clearly
      higher than that of normal cervix, making it possible to distinguish tumor tissue
      from normal cervical tissue. BF of the tumors after 20 Gy of radiation therapy
      calculated by the MS method was significantly larger than that before treatment
      (126.9 vs. 72.2 ml/min/100 ml, median; p < 0.05). Although BF calculated by the
      MS and SOCM methods showed a positive linear correlation (p < 0.001, r = 0.981),
      BF calculated by the MS method was lower than that obtained by the SOCM method
      (103.7 vs. 115.1 ml/min/100 ml, p < 0.01). The change of tumor BF in cervical
      cancer before and after radiation therapy can be monitored by conducting blood
      flow analysis using perfusion CT. BF by the MS method was lower than that by the
      SOCM method, but the two analytical methods correlated well. Perfusion CT may
      have potential in noninvasive monitoring of vascular and oxygenation status and
      for guiding adaptive therapy.

PMID- 21959831
TI  - From cells to systems: grids and boundaries in spatial memory.
AB  - How do we know where we are? Orientation in space is key to our daily existence
      as we follow familiar routes, navigate to a previous location, or just try to get
      home as quickly as possible. As well as being interesting in its own right,
      spatial cognition is also a useful model system in which to understand the neural
      bases of cognition and memory formation more generally. Spatial behavior offers
      potentially straightforward correlates of neuronal activity that can be studied
      similarly in adults and infants of both human and non-human animals. The neural
      mechanisms of spatial behavior can be realistically investigated in a well
      controlled way with the aid of virtual reality technologies in humans and
      rodents. Virtual reality can thus help to bridge the gap between
      electrophysiological studies in rodents and brain imaging studies using
      functional magnetic resonance imaging in humans. Within this framework, this
      article aims to translate findings from the single cell level in rodents to
      understand the neural and systems level mechanisms of spatial cognition in the
      human brain.

PMID- 21959832
TI  - Acute respiratory effects in firefighters.
AB  - BACKGROUND: Associations between acute respiratory inflammatory responses,
      changes in bronchial hyperresponsiveness, serum pneumoprotein levels, and
      exposure to fire smoke were studied. METHODS: The study comprised 51
      firefighters. Blood samples were taken within 24 hr following exposure to fire
      smoke, and after a week and 3 months. Sputum was induced within 5 days post
      exposure and subjects underwent spirometry and methacholine provocation one week
      post-exposure. Exposure was registered by a questionnaire. RESULTS: No changes
      were observed following smoke exposure in bronchial hyperresponsiveness and serum
      pneumoprotein levels. Nevertheless, in a sizable proportion of the firefighters
      (44%) elevated sputum neutrophil levels (>=60%) were found. Serum IL-8
      concentrations were higher 24 hr post-exposure compared to pre-exposure. Elevated
      neutrophil levels in sputum were associated with elevated serum IL-8 (beta =
      0.010, P = 0.004) and TNFalpha (beta = 0.005, P = 0.034) levels within 24 hr post
      exposure and IL-8 elevation lasted up to 3 months. CONCLUSIONS: Acute exposure to
      fire smoke induces acute neutrophilic airway and long-lasting systemic
      inflammation in healthy firefighters in the absence of bronchial
      hyperresponsiveness.

PMID- 21959833
TI  - Cervical pedicle screw placement using the "key slot technique": the feasibility
      and learning curve.
AB  - STUDY DESIGN: A retrospective study. OBJECTIVES: To present the accuracy and
      safety of a novel "key slot (KS)" technique for cervical pedicle screw (CPS)
      placement with the learning curve. SUMMARY OF BACKGROUND DATA: Safety and
      learning curve are the issues preventing wide acceptance of CPS. On the basis of
      the local anatomy of the pedicle, the authors modified the conventional technique
      to increase the accuracy and comfortableness of CPS placement with minimal bone
      loss. METHODS: A total of 277 subaxial CPS in 50 patients had been inserted using
      author's technique were reviewed. The KS-shaped entry was created on the medial
      half of the lateral mass with a 3 mm cutting burr. The shape of entry was a right
      angled triangle on the axial plane. The apex of triangle was the virtual pedicle
      inlet and the oblique side was same as pedicle axis. After making entry, the
      pedicle was probed with a curved awl along the medial wall. On the postoperative
      vascular-enhanced computed tomography scan, we analyzed the direction and grade
      of pedicle perforation (grade 0: no perforation, 1:< 25%, 2: 20% to 50%, 3: > 50%
      of screw diameter) on the chronological group of consecutive 10 cases. Grade 2
      and 3 were considered as incorrect position. RESULTS: The correct position was
      found in 250 screws (90.3%); grade 0 - 215 screws, 1 - 35 screws and the
      incorrect position in 27 screws (9.7%); grade 2 - 21 screws, grade 3 - 6 screws.
      The incidence of incorrect screw position was 18% in the initial 20 cases and
      2.7% after that. There was no neurovascular complication related with CPS.
      CONCLUSIONS: We performed CPS placement using the KS technique and with 90%
      correct position without clinical complications. After the learning curve, the
      incidence was 2.7%. This technique could be considered relatively concrete and
      safe modification of conventional technique with minimal bone loss.

PMID- 21959834
TI  - Relationship between the alignment of the occipitoaxial and subaxial cervical
      spine in patients with congenital atlantoxial dislocations.
AB  - STUDY DESIGN: Prospective radiographic analysis. OBJECTIVE: This study aimed to
      characterize the relationship between the alignment of the occipitoaxial (OA) and
      the subaxial spine, establish normal parameters, and to determine the influence
      of upper cervical spine alignment on subaxial degenerative disc disease (DDD) and
      clinical outcomes in this population. SUMMARY OF BACKGROUND DATA: Previous
      studies reported that the alignments of the upper and lower cervical spine are
      closely interrelated in patients with atlantoaxial dislocations of a rheumatoid
      etiology. None have focused on congenital etiologies or included patients with OA
      kyphosis. The influence of the upper cervical alignment on subaxial (DDD) and
      outcomes is also unclear. METHODS: Fifty-eight patients with congenital AAD
      undergoing surgical reduction and fusion were included. C0-C2 and C2-C7 angles
      were measured and DDD was assessed using plain radiographs. The relationship
      between the alignment of the OA joint and the subaxial cervical spine was
      evaluated, as well as the relationships between the cervical alignment, outcomes,
      and cervical DDD. RESULTS: C0-2 improved from a mean of 1.59+/-17.3 degrees
      preoperatively to a mean of 15+/-9.8 degrees postoperatively (P<0.001). C2-7
      changed from a mean of 25.55+/-19.6 degrees to a mean of 14.2+/-14.4 degrees
      postoperatively (P<0.001). The OA and subaxial alignment were negatively
      correlated in this population both before (r=-0.84; P<0.001) and after (r=-0.64;
      P<0.001) surgical treatment. There was an increased incidence of DDD
      postoperatively (P<0.01), which was positively correlated with the postoperative
      C0-2 angle (r=0.54; P<0.001), but negatively correlated with the postoperative C2
      7 angle (r=-0.79; P<0.001). CONCLUSIONS: Changes in OA alignment before and after
      surgery are associated with changes in the subaxial spine. There is a high
      incidence of postoperative DDD in the subaxial spine that seems to be related to
      sagittal alignment after surgery.

PMID- 21959835
TI  - Pedicle morphology using computed tomography-based navigation system in
      adolescent idiopathic scoliosis.
AB  - STUDY DESIGN/SETTING: Retrospective study. OBJECTIVE: The purpose of this study
      was to use multidimensional analysis with a computed tomography (CT)-based
      navigation system to measure the outer cortical diameter and the maximum screw
      trajectory length of the pedicle of the thoracic and lumbar regions of the spine
      in adolescent idiopathic scoliosis (AIS) patients. Another objective was to
      identify pedicles that require cautious insertion of screws. SUMMARY OF
      BACKGROUND DATA: Pedicle diameter in AIS patients was narrower on the concave
      side of the scoliotic curve. Many researchers have measured pedicle diameter and
      length of AIS patients by using standard CT or magnetic resonance imaging (MRI),
      but only few have used 3-dimensional imaging, especially CT-based navigation.
      METHODS: Fifteen patients with right-side thoracic AIS who underwent pedicle
      screw fixation were studied. A CT-based navigation system was used to measure the
      pedicle diameter, defined as the widest outer cortical diameter at the narrowest
      part of the pedicle. Moreover, the maximum pedicle screw trajectory length was
      measured as the distance between the posterior cortical entry point of the
      pedicle screw and the anterior vertebral cortex in line with the axis of the
      pedicle between T1 and L5. In addition, the values of each parameter taken using
      the CT navigation system and the standard axial CT were compared. RESULTS:
      Pedicles on the concave side of the main thoracic curve apex and proximal
      thoracic curve tended to have the narrowest diameters. The mean length of the
      longest screw that could be fixed was longer on the right side, except for T8 and
      T9. Our data showed screw size feasibility as follows: 25 or 30 mm screws were
      feasible from T1 to T5; 30 or 35 mm screws, from T6 to T12; and 35 or 40 mm
      screws, from L1 to L5. Pedicle diameter measured by the CT navigation system was
      larger than that measured by standard axial CT. Left-side pedicle length measured
      by the CT navigation system was lesser than that measured by standard axial CT.
      CONCLUSIONS: Pedicle diameter in patients with AIS is narrower on the concave
      side of the scoliotic curve, and therefore, caution should be exercised during
      screw insertion on the concave side.

PMID- 21959836
TI  - Adjacent segment degeneration after lumbar dynamic stabilization using pedicle
      screws and a nitinol spring rod system with 2-year minimum follow-up.
AB  - STUDY DESIGN: Prospective study evaluating the adjacent segment degeneration
      after lumbar dynamic stabilization using pedicle screws and a Nitinol spring rod
      system. OBJECTIVE: To assess the changes of the adjacent and implantation
      segments after lumbar dynamic stabilization surgery using magnetic resonance
      imaging (MRI). SUMMARY OF BACKGROUND DATA: Lumbar fusion operations can
      accelerate the degeneration of adjacent levels. Recently, motion preservation
      surgery has been attempted for the treatment of lumbar degenerative diseases to
      prevent degeneration of adjacent levels. However, there is a controversy over
      whether lumbar dynamic stabilization accelerates degeneration of adjacent levels.
      METHODS: We performed the dynamic stabilization procedure in patients with grade
      1 degenerative lumbar spondylolisthesis, lumbar spondylotic stenosis with
      segmental instability, or a herniated lumbar disc with segmental instability.
      Postoperative MRI scans were taken for >2 years in all enrolled 25 patients. We
      compared the findings regarding disc degeneration in the cranial, implantation,
      and caudal segments between the preoperative period and 2-year-plus postoperative
      period using T2-weighted sagittal MR images. In addition, we investigated the
      progression of the central and foraminal stenosis of the adjacent cranial and
      caudal levels. RESULTS: Three of the 25 cranial adjacent discs (12.0%) and 4 of
      the 25 (16%) caudal adjacent discs demonstrated progression of degeneration after
      dynamic stabilization. One of the 13 discs in the implantation segment
      demonstrated progression of degeneration, and 2 of the 13 discs in the
      implantation segment showed improvement of their disc degeneration (disc
      rehydration). A total of 5 (10.0%) of the 50 segments (3 cranial and 2 caudal
      adjacent) showed increased spinal stenosis postoperatively. Among the 5 cases, 3
      patients had symptomatic adjacent stenosis. CONCLUSION: According to our results,
      lumbar dynamic stabilization using pedicle screws and a Nitinol spring rod system
      may not prevent adjacent level degeneration completely.

PMID- 21959837
TI  - Clinical evaluation of anterior screw fixation for elderly patients with type II
      odontoid fractures.
AB  - STUDY DESIGN: A retrospective study of elderly patients who underwent anterior
      screw fixation for type II odontoid fractures between 2000 and 2009 was
      conducted. OBJECTIVE: To evaluate the clinical outcome of anterior screw fixation
      for type II odontoid fractures in elderly people and to provide valuable
      information for spinal surgeon reference. SUMMARY OF BACKGROUND DATA: Odontoid
      fractures are the most common fractures of the cervical spine in patients above
      70 years of age, and patients above 80 years of age form the majority of spinal
      fractures. However, the optimum treatment of type II odontoid fractures in the
      geriatric population remains controversial. METHODS: A retrospective analysis was
      performed in 43 patients (19 women; mean age, 80.6 y; range, 65 to 92 y) with
      type II odontoid fractures who were consecutively admitted to a single medical
      center between January 2000 and October 2009. Twenty-eight patients had
      posteriorly displaced odontoid fractures and the remaining 15 had anteriorly
      displaced odontoid fractures according to the radiographical presentation.
      Neurological symptoms were present in 4 patients including 3 Frankel D and 1
      Frankel C and always occurred in patients with posteriorly displaced odontoid
      process. The medical records, plain x-rays, and computed tomographic scans of all
      patients were reviewed. After surgery, patients were discharged with rigid
      cervical immobilization and clinical follow-ups were between 18 and 24 months
      (average, 21.3 mo). RESULTS: The mean displacement of odontoid process revealed
      by preoperative radiologic evaluation was 4.9 mm (ranged from 1 to 10 mm).
      Anterior screw fixation was performed successfully in 42 cases except 1 in which
      posterior C1-C2 fusion had to be undertaken to replace the original operation
      scheme because of technical difficulty. According to postoperative radiologic
      evaluation, 36 of 42 type II odontoid fracture cases treated with anterior screw
      fixation achieved fusion within 6 months. The fusion rate was 85.7% (36 of 42).
      Thirty-four patients regained normal cervical movement, 5 patients had about 25%,
      and 3 had >25% limited cervical motion. Sixteen patients achieved clinically
      excellent outcomes, 24 good, and 2 fair outcomes. CONCLUSIONS: Anterior screw
      fixation can be performed safely in elderly patients with type II odontoid
      fracture, and the clinical outcomes of this procedure were satisfactory. High
      fusion rates, low postoperative complications, and maintenance of cervical motion
      were acquired. The anterior screw fixation can be a reliable and reasonable
      treatment for type II odontoid fractures in the elderly patients.

PMID- 21959838
TI  - Minimal-invasive percutaneous reduction and transsacral screw fixation for U
      shaped fractures.
AB  - STUDY DESIGN: Technical note and case series. OBJECTIVE: To introduce an
      innovative minimal-invasive surgical procedure reducing surgery time and blood
      loss in management of U-shaped sacrum fractures. SUMMARY OF BACKGROUND: Despite
      their seldom appearance, U-shaped fractures can cause severe neurological
      deficits and surgical management difficulties. According to the nature of the
      injury normally occurring in multi-injured patients after a fall from height, a
      jump, or road traffic accident, U-shaped fractures create a spinopelvic
      dissociation and hence are highly unstable. In the past, time-consuming open
      procedures like large posterior constructs or shortening osteotomies with or
      without decompression were the method of choice, sacrificing spinal mobility.
      Insufficient restoration of sacrococcygeal angle and pelvic incidence with
      conventional techniques may have adverse long-term effects in these patients.
      METHODS: In a consecutive series of 3 patients, percutaneous reduction of the
      fracture with Schanz pins inserted in either the pedicles of L5 or the S1 body
      and the posterior superior iliac crest was achieved. The Schanz pins act as
      lever, allowing a good manipulation of the fracture. The reduction is secured by
      a temporary external fixator to permit optimal restoration of pelvic incidence
      and sacral kyphosis. Insertion of 2 transsacral screws allow fixation of the
      restored spinopelvic alignment. RESULTS: Anatomic alignment of the sacrum was
      possible in each case. Surgery time ranged from 90 to 155 minutes and the blood
      loss was <50 mL in all 3 cases. Two patients had very good results in the long
      term regarding maintenance of pelvic incidence and sacrococcygeal angle. One
      patient with previous cauda equina decompression had loss of correction after 6
      months. CONCLUSIONS: Percutaneous reduction and transsacral screw fixation offers
      a less invasive method for treating U-shaped fractures. This can be advantageous
      in treatment of patients with multiple injuries.

PMID- 21959839
TI  - Does the lower instrumented vertebra have an effect on lumbar mobility,
      subjective perception of trunk flexibility, and quality of life in patients with
      idiopathic scoliosis treated by spinal fusion?
AB  - STUDY DESIGN: Cross-sectional study in patients with idiopathic scoliosis treated
      with spinal fusion. OBJECTIVES: To measure lumbar spine mobility in the study
      population; determine low back pain intensity (LBPi), subjective perception of
      trunk flexibility (TF), and quality of life using validated outcome instruments;
      and investigate correlations of the lower instrumented vertebra (LIV) with TF,
      LBPi, and quality of life. SUMMARY OF BACKGROUND DATA: The loss of range of
      motion resulting from spinal fusion might lead to low back pain, trunk rigidity,
      and a negative impact on quality of life. Nonetheless, these outcomes have not
      been conclusively demonstrated because lumbar mobility and LIV have not been
      correlated with validated outcome instruments. METHODS: Forty-one patients (mean
      age, 27 y) with idiopathic scoliosis treated by spinal fusion (mean time since
      surgery, 135 mo) were included. Patients were assigned to 3 groups according to
      LIV level: group 1 (fusion to T12, L1, or L2) 14 patients; group 2 (fusion to L3)
      13 patients, and group 3 (fusion to L4, L5, or S1) 14 patients. At midterm follow
      up, patients completed the Scoliosis Research Society (SRS)-22 Questionnaire and
      Quality of Life Profile for Spine Deformities to evaluate perceived TF, and rated
      LBPi with a numerical scale. Lumbar mobility was assessed using a dual digital
      inclinometer. RESULTS: Group 3 (fusion to L4, L5, or S1) showed statistically
      significant differences relative to the other groups, with less lumbar mobility
      and poorer scores for the SRS subtotal (P = 0.003) and SRS pain scale (P = 0.01).
      Nevertheless, LBPi and TF were similar in the 3 groups. TF correlated with SRS-22
      subtotal (r = -0.38, P = 0.01) and pain scale (r = -0.42, P = 0.007) scores, and
      with LBPi (r = 0.43, P = 0.005). CONCLUSIONS: LIV correlated moderately with
      lumbar mobility, health-related quality of life (SRS-22), and spinal pain (SRS-22
      pain subscale), but not with intensity of pain in the lumbar area or perceived
      TF.

PMID- 21959840
TI  - Cost-utility analysis of minimally invasive versus open multilevel
      hemilaminectomy for lumbar stenosis.
AB  - STUDY DESIGN: Two-year cost-utility study comparing minimally invasive (MIS)
      versus open multilevel hemilaminectomy in patients with degenerative lumbar
      spinal stenosis. OBJECTIVE: The objective of the study was to determine whether
      MIS versus open multilevel hemilaminectomy for degenerative lumbar spinal
      stenosis is a cost-effective advancement in lumbar decompression surgery. SUMMARY
      OF BACKGROUND DATA: MIS-multilevel hemilaminectomy for degenerative lumbar spinal
      stenosis allows for effective treatment of back and leg pain while theoretically
      minimizing blood loss, tissue injury, and postoperative recovery. No studies have
      evaluated comprehensive healthcare costs associated with multilevel
      hemilaminectomy procedures, nor assessed cost-effectiveness of MIS versus open
      multilevel hemilaminectomy. METHODS: Fifty-four consecutive patients with lumbar
      stenosis undergoing multilevel hemilaminectomy through an MIS paramedian tubular
      approach (n=27) versus midline open approach (n=27) were included. Total back
      related medical resource utilization, missed work, and health state values
      [quality adjusted life years (QALYs), calculated from EuroQuol-5D with US
      valuation] were assessed after 2-year follow-up. Two-year resource use was
      multiplied by unit costs based on Medicare national allowable payment amounts
      (direct cost) and work-day losses were multiplied by the self-reported gross-of
      tax wage rate (indirect cost). Difference in mean total cost per QALY gained for
      MIS versus open hemilaminectomy was assessed as incremental cost-effectiveness
      ratio (ICER: COST(MIS)-COST(OPEN)/QALY(MIS)-QALY(OPEN)). RESULTS: MIS versus open
      cohorts were similar at baseline. MIS and open hemilaminectomy were associated
      with an equivalent cumulative gain of 0.72 QALYs 2 years after surgery. Mean
      direct medical costs, indirect societal costs, and total 2-year cost ($23,109 vs.
      $25,420; P=0.21) were similar between MIS and open hemilaminectomy. MIS versus
      open approach was associated with similar total costs and utility, making it a
      cost equivalent technology compared with the traditional open approach.
      CONCLUSIONS: MIS versus open multilevel hemilaminectomy was associated with
      similar cost over 2 years while providing equivalent improvement in QALYs. In our
      experience, MIS versus open multilevel hemilaminectomy is a cost equivalent
      technology for patients with lumbar stenosis-associated radicular pain.

PMID- 21959841
TI  - Ab initio study of isolated chlorine defects in cubic SiC.
AB  - The electronic properties and formation energy of isolated Cl defects in SiC were
      investigated by first-principles calculations. Chlorine was studied in a
      substitutional position, in either a carbon (Cl(C)) or a silicon site (Cl(Si)),
      and in two interstitial positions (Cl(i)), either tetrahedral or octahedral
      configurations. Our calculations revealed that Cl(C) is energetically favored and
      it is a likely candidate to explain the nature of the experimentally observed Cl
      incorporation reported in SiC epilayers grown by chloride-based chemical vapor
      deposition.

PMID- 21959842
TI  - Nutritional status, acute phase response and depression in metastatic lung cancer
      patients: correlations and association prognosis.
AB  - BACKGROUND AND AIM: Cancer cachexia is a metabolic syndrome related with poor
      outcome. Cytokines play a key role in the pathophysiology of that syndrome. The
      aim of this study was to investigate the potential correlations between
      nutritional status, systemic inflammation, and psychological distress in cancer
      patients. The prognostic significance of the recorded parameters was also
      assessed. PATIENTS AND METHODS: Patients with metastatic lung cancer were
      eligible. Mini Nutritional Assessment (MNA) was used for the evaluation of
      nutritional status, Glasgow Prognostic Score (GPS) for the estimation of systemic
      inflammation, and Hospital Anxiety and Depression Scale (HADS) for psychological
      assessment. RESULTS: Totally, 122 patients were enrolled (71.3% with NSCLC and
      28.7% with SCLC). The following correlations were observed: MNA and GPS (r =
      0.289, p = 0.001), MNA and HADS (depression scale) (r = 0.275, p = 0.002), GPS
      and HADS (depression scale) (r = 0.256, p = 0.004), and GPS and HADS (anxiety
      scale) (r =0.194, p =0.033). In univariate analysis, GPS (p = 0.002) and MNA (p =
      0.010) emerged as significant predictors of survival. In multivariate analysis,
      both MNA (p = 0.032) and GPS (p = 0.020) retained their importance. CONCLUSIONS:
      This study highlights the associations between nutritional status, systemic
      inflammation, and psychological distress, supporting their common underlying
      pathophysiological mechanisms and further suggesting the necessity of a holistic
      anti-cachectic approach.

PMID- 21959843
TI  - Skeletal evidence for Inca warfare from the Cuzco region of Peru.
AB  - This article addresses the bioarchaeological evidence for Inca warfare through an
      analysis of 454 adult skeletons from 11 sites in the Inca capital region of
      Cuzco, Peru. These 11 sites span almost 1000 years (AD 600-1532), which allows
      for a comparison of the evidence for warfare before the Inca came to power
      (Middle Horizon AD 600-1000), during the time of Inca ascendency in the Late
      Intermediate Period (AD 1000-1400), and after the Inca came to power and expanded
      throughout the Cuzco region and beyond (Inca Imperial Period, AD 1400-1532). The
      results indicate that 100 of 454 adults (22.0%) showed evidence of cranial
      trauma. Of these, 23 individuals had major cranial injuries suggestive of
      warfare, consisting of large, complete, and/or perimortem fractures. There was
      scant evidence for major injuries during the Middle Horizon (2.8%, 1/36) and Late
      Intermediate Period (2.5%, 5/199), suggesting that warfare was not prevalent in
      the Cuzco region before and during the Inca rise to power. Only in the Inca
      Imperial Period was there a significant rise in major injuries suggestive of
      warfare (7.8%, 17/219). Despite the significant increase in Inca times, the
      evidence for major cranial injuries was only sporadically distributed at Cuzco
      periphery sites and was entirely absent at Cuzco core sites. These findings
      suggest that while the Inca used warfare as a mechanism for expansion in the
      Cuzco region, it was only one part of a complex expansion strategy that included
      economic, political, and ideological means to gain and maintain control.

PMID- 21959844
TI  - The critical importance of size on thermoresponsive nanoparticle transition
      temperatures: gold and micelle-based polymer nanoparticles.
AB  - The synthesis and application of thermally-responsive macromolecules and
      nanoparticles relies on the underpinning control of their transition
      temperatures. The present study shows that two structurally diverse classes of
      nanoparticle have very strong diameter-dependent responses to temperature
      stimuli, demonstrating that the exact size of the nanostructure can significantly
      impact its performance.

PMID- 21959845
TI  - Establishment and characterization of fibroblast cell lines from the skin of the
      Yangtze finless porpoise.
AB  - The Yangtze finless porpoise (Neophocaena phocaenoides asiaeorientalis), as the
      sole freshwater subspecies of N. phocaenoides, is endemic to the Yangtze River
      and its adjacent lakes. Its population has declined significantly over recent
      decades. In this study, we established a skin-derived finite fibroblast cell line
      of the Yangtze finless porpoise, named YFP-SF1, using primary cell culture
      methods, and an immortalized cell line, T-YFP-SF1, through co-transfection (GFP
      and SV40 T antigens) techniques. YFP-SF1 proliferated continuously with a minimum
      population doubling time of 31 h and exhibited age-dependent changes in growth
      rate. T-YFP-SF1 cells exhibited fibroblast morphology and were characterized by a
      shorter doubling time, higher attachment efficiencies, colony formation at a low
      seeding density, and growth in low serum concentrations. Anchorage independence
      and foci formation in the cell monolayer were observed from passage 36. The
      chromosome number of YFP-SF1 and T-YFP-SF1 remained stable at 2n = 44 in the
      early passages, and the viability of thawed cells remained above 90% after
      cryopreservation in liquid nitrogen. Taken together, we have established
      fibroblast cell lines of Yangtze finless porpoise for the first time, which might
      assist as an in vitro model for this endangered mammal.

PMID- 21959846
TI  - Optimization of gene delivery methods in Xenopus laevis kidney (A6) and Chinese
      hamster ovary (CHO) cell lines for heterologous expression of Xenopus inner ear
      genes.
AB  - The Xenopus inner ear provides a useful model for studies of hearing and balance
      because it shares features with the mammalian inner ear, and because amphibians
      are capable of regenerating damaged mechanosensory hair cells. The structure and
      function of many proteins necessary for inner ear function have yet to be
      elucidated and require methods for analysis. To this end, we seek to characterize
      Xenopus inner ear genes outside of the animal model through heterologous
      expression in cell lines. As part of this effort, we aimed to optimize physical
      (electroporation), chemical (lipid-mediated; LipofectamineTM 2000, Metafectene(r)
      Pro), and biological (viral-mediated; BacMam virus Cellular LightsTM Tubulin-RFP)
      gene delivery methods in amphibian (Xenopus; A6) cells and mammalian (Chinese
      hamster ovary (CHO)) cells. We successfully introduced the commercially available
      pEGFP-N3, pmCherry-N1, pEYFP-Tubulin, and Cellular LightsTM Tubulin-RFP
      fluorescent constructs to cells and evaluated their transfection or transduction
      efficiencies using the three gene delivery methods. In addition, we analyzed the
      transfection efficiency of a novel construct synthesized in our laboratory by
      cloning the Xenopus inner ear calcium-activated potassium channel beta1 subunit,
      then subcloning the subunit into the pmCherry-N1 vector. Every gene delivery
      method was significantly more effective in CHO cells. Although results for the A6
      cell line were not statistically significant, both cell lines illustrate a trend
      towards more efficient gene delivery using viral-mediated methods; however the
      cost of viral transduction is also much higher. Our findings demonstrate the need
      to improve gene delivery methods for amphibian cells and underscore the necessity
      for a greater understanding of amphibian cell biology.

PMID- 21959847
TI  - Induction of insulin-like growth factor 2 expression in a mesenchymal cell line
      co-cultured with an ameloblast cell line.
AB  - Various growth factors have been implicated in the regulation of cell
      proliferation and differentiation during tooth development. It has been unclear
      if insulin-like growth factors (IGFs) participate in the epithelium-mesenchyme
      interactions of tooth development. We previously produced three-dimensional
      sandwich co-culture systems (SW) containing a collagen membrane that induce the
      differentiation of epithelial cells. In the present study, we used the SW system
      to analyze the expression of IGFs and IGFRs. We demonstrate that IGF2 expression
      in mesenchymal cells was increased by SW. IGF1R transduces a signal; however,
      IGF2R does not transduce a signal. Recombinant IGF2 induces IGF1R and IGF2R
      expression in epithelial cells. IGF1R expression is increased by SW; however,
      IGF2R expression did not increase by SW. Thus, IGF2 signaling works effectively
      in SW. These results suggest that IGF signaling acts through the collagen
      membrane on the interaction between the epithelium and mesenchyme. In SW, other
      cytokines may be suppressed to induce IGF2R induction. Our results suggest that
      IGF2 may play a role in tooth differentiation.

PMID- 21959848
TI  - Quantitative analysis of videokymography in normal and pathological vocal folds:
      a preliminary study.
AB  - Videokymography (VKG) captures high-speed images of the vocal folds independently
      of the periodicity of the acoustic signal. The aim of this study was to
      preliminarily assess a software package that can objectively measure specific
      parameters of vocal fold vibration. From August 2009 until December 2010, we
      prospectively evaluated 40 subjects (Group A, 18 normal subjects; Group B, 14
      patients with benign lesions of the middle third of the vocal fold, such as
      polyps and cysts; Group C, 8 patients treated by endoscopic excision of vocal
      fold benign lesions) by videoendoscopy, videolaryngostroboscopy, and VKG. A VKG
      camera was coupled to a 70 degrees  telescope and video was recorded during
      phonation. Images were objectively analyzed by a post-processing software tool
      (VKG-Analyser) with a user-friendly interface developed by our group. Different
      parameters were considered, including the ratio between the amplitude of the
      vibration of one vocal fold with respect to the contralateral (R(amp)), the ratio
      between the period of one vocal fold vibration and the opposite one (R(per)), and
      the ratio between the duration of the open and closed phase within a glottal
      cycle (R(oc)). Mean values for R(amp), R(per), and R(oc) in Group A were 1.05,
      1.04, and 1.35, respectively; in Group B were 1.63, 0.92, and 0.97, respectively;
      and in Group C were 1.13, 0.91, and 1.85, respectively. Quantitative analysis of
      videokymograms by the herein presented tool, named VKG-Analyser, is useful for
      objective evaluation of the vibratory pattern in normal and pathologic vocal
      folds. Important future developments of this tool for the study of both
      physiologic and pathologic patterns of vocal fold vibration can be expected.

PMID- 21959850
TI  - Glucoraphanin does not reduce plasma homocysteine in rats with sufficient Se
      supply via the induction of liver ARE-regulated glutathione biosynthesis enzymes.
AB  - Data from human and animal trials have revealed contradictory results regarding
      the influence of selenium (Se) status on homocysteine (HCys) metabolism. It was
      hypothesised that sufficient Se reduces the flux of HCys through the
      transsulphuration pathway by decreasing the expression of glutathione (GSH)
      synthesising enzymes. Glucoraphanin (GRA) is a potent inducer of genes regulated
      via an antioxidant response element (ARE), including those of GSH biosynthesis.
      We tested the hypothesis that GRA supplementation to rat diets lowers plasma HCys
      levels by increasing GSH synthesis. Therefore 96 weaned albino rats were assigned
      to 8 groups of 12 and fed diets containing four different Se levels (15, 50, 150
      and 450 MUg kg(diet)(-1)), either without GRA (groups: C15, C50, C150 and C450)
      or in combination with 700 MUmol GRA kg(diet)(-1) (groups G15, G50, G150 and
      G450). Rats fed the low Se diets C15 and G15 showed an impressive decrease of
      plasma HCys. Se supplementation increased plasma HCys and lowered GSH
      significantly by reducing the expression of GSH biosynthesis enzymes. As new
      molecular targets explaining these results, we found a significant down
      regulation of the hepatic GSH exporter MRP4 and an up-regulation of the HCys
      exporter Slco1a4. In contrast to our hypothesis, GRA feeding did not reduce
      plasma HCys levels in Se supplemented rats (G50, G150 and 450) through inducing
      GSH biosynthesis enzymes and MRP4, but reduced their mRNA in some cases to a
      higher extent than Se alone. We conclude: 1. That the long-term supplementation
      of moderate GRA doses reduces ARE-driven gene expression in the liver by
      increasing the intestinal barrier against oxidative stress. 2. That the up
      regulation of ARE-regulated genes in the liver largely depends on GRA cleavage to
      free sulforaphane and glucose by plant-derived myrosinase or bacterial beta
      glucosidases. As a consequence, higher dietary GRA concentrations should be used
      in future experiments to test if GRA or sulforaphane can be established as HCys
      lowering compounds.

PMID- 21959856
TI  - [Possibilities for surgical correction of an anastomotic stricture after radical
      prostatectomy].
AB  - BACKGROUND: Anastomotic strictures following radical prostatectomy for prostate
      cancer are reported in about 1-8% of all patients. Endourologic management
      usually does not result in very high cure rates but is associated with very high
      rates of recurrences. There is no standard management of these postoperative long
      term complications and quite often the patient ends up having a transurethral or
      suprapubic catheter as a simple long-term solution. RESULTS: Twenty-four patients
      with recurrent anastomotic strictures and a mean of 3.5 (2-9) previous
      transurethral surgical interventions were operated between 2004 and 2011. All
      patients underwent perineal bladder neck closure and a continent vesicostomy with
      either an appendiceal or an ileal stoma implanted in the bladder. The mean OR
      time was 125 (100-195) min, and the mean time of hospitalisation was 12.5 (9-27)
      days. There were no significant intra- or perioperative complications. Three
      patients developed a significant urinary tract infection, two patients had to be
      treated for the development of a paralytic ileus and one patient needed to
      undergo revision surgery for a urethral fistula. After a mean follow-up of 37 (10
      78) months, two patients developed a stomal stenosis which was corrected
      surgically. CONCLUSIONS: Based on our experience, bladder neck closure and
      continent vesicostomy represent a valuable therapeutic option in the management
      of recurrent anastomotic strictures following radical prostatectomy.

PMID- 21959858
TI  - Applying the conjugated circuits method to Clar structures of [n]phenylenes for
      determining resonance energies.
AB  - We consider the aromaticity of biphenylene and structurally related linear or
      angular [n]phenylenes for which the direct application of the model of conjugated
      circuits does not offer valid expressions for resonance energy and aromaticity.
      We located the cause of this problem as being due to Kekule valence structures in
      which neighboring benzenoid rings are connected by two CC double bonds. By
      restricting the selection of Kekule valence structures to those that contribute
      to Clar structures of such systems, we were able to show that linear and angular
      [n]phenylenes have approximately similar resonance energies, with angular
      [n]phenylenes being slightly more stable due to second order contributions
      arising from disjoint conjugated circuits. Expressions for resonance energies of
      [n]phenylenes up to n = 8 are listed and recursion expressions for higher n
      values are outlined.

PMID- 21959857
TI  - Protein phosphatase 2A affects myofilament contractility in non-failing but not
      in failing human myocardium.
AB  - Protein phosphatase (PP) type 2A is a multifunctional serine/threonine
      phosphatase that is involved in cardiac excitation-contraction coupling. The PP2A
      core enzyme is a dimer, consisting of a catalytic C and a scaffolding A subunit,
      which is targeted to several cardiac proteins by a regulatory B subunit. At
      present, it is controversial whether PP2A and its subunits play a critical role
      in end-stage human heart failure. Here we report that the application of purified
      PP2AC significantly increased the Ca2+-sensitivity (DeltapCa50=0.05+/-0.01) of
      the contractile apparatus in isolated skinned myocytes of non-failing (NF)
      hearts. A higher phosphorylation of troponin I (cTnI) was found at protein kinase
      A sites (Ser23/24) in NF compared to failing myocardium. The basal Ca2+
      responsiveness of myofilaments was enhanced in myocytes of ischemic (ICM,
      DeltapCa50=0.10+/-0.03) and dilated (DCM, DeltapCa50=0.06+/-0.04) cardiomyopathy
      compared to NF. However, in contrast to NF myocytes the treatment with PP2AC did
      not shift force-pCa relationships in failing myocytes. The higher basal Ca2+
      sensitivity in failing myocytes coincided with a reduced protein expression of
      PP2AC in left ventricular tissue from patients suffering from ICM and DCM (by 50
      and 56% compared to NF, respectively). However, PP2A activity was unchanged in
      failing hearts despite an increase of both total PP and PP1 activity. The
      expression of PP2AB56alpha was also decreased by 51 and 62% in ICM and DCM
      compared to NF, respectively. The phosphorylation of cTnI at Ser23/24 was reduced
      by 66 and 49% in ICM and DCM compared to NF hearts, respectively. Our results
      demonstrate that PP2A increases myofilament Ca2+-sensitivity in NF human hearts,
      most likely via cTnI dephosphorylation. This effect is not present in failing
      hearts, probably due to the lower baseline cTnI phosphorylation in failing
      compared to non-failing hearts.

PMID- 21959859
TI  - Selective cognitive impairment and tall stature due to chromosome 19
      supernumerary ring.
AB  - Small supernumerary marker chromosomes (sSMC) occur with a frequency of
      approximately 0.4 per 1000 newborns and are more frequent in the population with
      mental retardation and/or with dysmorphic signs. Small supernumerary chromosome
      rings (sSCR) usually occur as apart of a mosaic karyotype (Liehr et al., 2004).
      Chromosome 19 supernumerary rings are very rare. Almost all cases of sSMC19 have
      been reported on Thomas Liehr's website (http://www.med.uni
      jena.de/fish/sSMC/19.htm#Start19). Of these cases, 14 were with phenotypic
      abnormalities and a clear characterization of the sSMC; two cases were suitable
      for comparison with our case with regard to their genetic content, but not with
      regard to the structure ofthe sSMC (Manvelyan et al., 2008). The phenotype,
      associated with partial trisomy 19q, includes facial dysmorphism, growth and
      mental retardation, macrocephaly, heart malformation and anomalies of the
      genitourinary and gastrointestinal tracts. The phenotype associated with partial
      trisomy 19p is characterized by dysmorphic features, severe mental retardation,
      abnormalities of brain morphology and anomalies of the fingers (Tercanli et al.,
      2000; Qorri et al., 2002; Novelli et al., 2005; Vranekovic et al., 2008). Herein,
      we report the phenotype and molecular cytogenetic analysis in a patient with the
      smallest de-novo constitutional ring extended from the p12 to q12 region of
      chromosome 19.

PMID- 21959860
TI  - Isolated macrodystrophia lipomatosa of the foot in a neonate:  a case report.
AB  - Macrodystrophia lipomatosa characterized by enlargement of one or more fingers or
      toes with predominantly fibroadipose tissue can be part of an overgrowth syndrome
      such as Proteus syndrome (Biesecker, 2006) or CLOVES syndrome (Sapp et al., 2007;
      Alomari, 2009) or found as an isolated abnormality in an otherwise normal
      patient. It maybe present at birth or occur in early infancy with a progressive
      course. Here, we report a case of macrodystrophia lipomatosa (MDL) diagnosed in
      the neonatal period in a baby who had no other apparent problems on follow-up.

PMID- 21959861
TI  - Well-defined clinical presentation of Ehlers-Danlos syndrome in patients with
      tenascin-X deficiency:  a report of four cases.
AB  - The Ehlers-Danlos syndrome (EDS) is a clinically and genetically heterogeneous
      group of inherited connective tissue disorders. The six major, well-defined,
      subtypes are classified according to diagnostic criteria, formalized in the
      Villefranche revised nosology. Shortly after the publication of these criteria in
      1998, a further distinct type of EDS, the tenascin-X (TNX)-deficient type EDS,
      was reported. The phenotype of this largely unknown type of EDS resembles the
      phenotype of the classical type of EDS, but its inheritance is autosomal
      recessive and wound healing is normal; hence, no atrophic scars are present. The
      clinical diagnosis can be confirmed by the absence of TNX in the serum and by
      mutation analysis of the TNXB gene. Because the TNX-deficient type EDS is rare
      and not included in the current diagnostic criteria, this diagnosis is often
      delayed or even overlooked. Here, we describe four cases which improve the
      clinical recognition of this type of EDS.

PMID- 21959862
TI  - Unusual physical features and heat stroke presentation for hypohydrotic
      ectodermal dysplasia.
AB  - Hypohidrotic/ anhidrotic ectodermal dysplasia (HED) is characterized by
      hypotrichosis (sparseness of scalp and body hair), hypohidrosis (reduced ability
      to sweat), and hypodontia (decreased tooth development). Sweating is either
      absent or greatly deficient leading to an increased risk for hyperthermia. This
      is a relatively common genetic condition; it is estimated that 1 in approximately
      5000-10 000 newborns has HED (Wright et al., 2009). Here, we report an infant
      with HED who presented with a heat stroke-like condition in the extreme winter
      months of Michigan.

PMID- 21959863
TI  - Layered nanocomposites inspired by the structure and mechanical properties of
      nacre.
AB  - Nacre (mother-of-pearl), made of inorganic and organic constituents (95 vol%
      aragonite calcium carbonate (CaCO(3)) platelets and 5 vol% elastic biopolymers),
      possesses a unique combination of remarkable strength and toughness, which is
      compatible for conventional high performance materials. The excellent mechanical
      properties are related to its hierarchical structure and precisely designed
      organic-inorganic interface. The rational design of aragonite platelet strength,
      aspect ratio of aragonite platelets, and interface strength ensures that the
      strength of nacre is maximized under platelet pull-out failure mode. At the same
      time, the synergy of strain hardening mechanisms acting over multiple scales
      results in platelets sliding on one another, and thus maximizes the energy
      dissipation of viscoplastic biopolymers. The excellent integrated mechanical
      properties with hierarchical structure have inspired chemists and materials
      scientists to develop biomimetic strategies for artificial nacre materials. This
      critical review presents a broad overview of the state-of-the-art work on the
      preparation of layered organic-inorganic nanocomposites inspired by nacre, in
      particular, the advantages and disadvantages of various biomimetic strategies.
      Discussion is focused on the effect of the layered structure, interface, and
      component loading on strength and toughness of nacre-mimic layered nanocomposites
      (148 references).

PMID- 21959864
TI  - Highly efficient deep-blue electrophosphorescence enabled by solution-processed
      bipolar tetraarylsilane host with both a high triplet energy and a high-lying
      HOMO level.

PMID- 21959865
TI  - NetSlim: high-confidence curated signaling maps.
AB  - We previously developed NetPath as a resource for comprehensive manually curated
      signal transduction pathways. The pathways in NetPath contain a large number of
      molecules and reactions which can sometimes be difficult to visualize or
      interpret given their complexity. To overcome this potential limitation, we have
      developed a set of more stringent curation and inclusion criteria for pathway
      reactions to generate high-confidence signaling maps. NetSlim is a new resource
      that contains this 'core' subset of reactions for each pathway for easy
      visualization and manipulation. The pathways in NetSlim are freely available at
      http://www.netpath.org/netslim.

PMID- 21959867
TI  - The NIDDK Central Repository at 8 years--ambition, revision, use and impact.
AB  - The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
      Central Repository makes data and biospecimens from NIDDK-funded research
      available to the broader scientific community. It thereby facilitates: the
      testing of new hypotheses without new data or biospecimen collection; pooling
      data across several studies to increase statistical power; and informative
      genetic analyses using the Repository's well-curated phenotypic data. This
      article describes the initial database plan for the Repository and its revision
      using a simpler model. Among the lessons learned were the trade-offs between the
      complexity of a database design and the costs in time and money of
      implementation; the importance of integrating consent documents into the basic
      design; the crucial need for linkage files that associate biospecimen IDs with
      the masked subject IDs used in deposited data sets; and the importance of
      standardized procedures to test the integrity data sets prior to distribution.
      The Repository is currently tracking 111 ongoing NIDDK-funded studies many of
      which include genotype data, and it houses over 5 million biospecimens of more
      than 25 types including serum, plasma, stool, urine, DNA, red blood cells, buffy
      coat and tissue. Repository resources have supported a range of biochemical,
      clinical, statistical and genetic research (188 external requests for clinical
      data and 31 for biospecimens have been approved or are pending). Genetic research
      has included GWAS, validation studies, development of methods to improve
      statistical power of GWAS and testing of new statistical methods for genetic
      research. We anticipate that the future impact of the Repository's resources on
      biomedical research will be enhanced by (i) cross-listing of Repository
      biospecimens in additional searchable databases and biobank catalogs; (ii)
      ongoing deployment of new applications for querying the contents of the
      Repository; and (iii) increased harmonization of procedures, data collection
      strategies, questionnaires etc. across both research studies and within the
      vocabularies used by different repositories.

PMID- 21959866
TI  - 3DSwap: curated knowledgebase of proteins involved in 3D domain swapping.
AB  - Three-dimensional domain swapping is a unique protein structural phenomenon where
      two or more protein chains in a protein oligomer share a common structural
      segment between individual chains. This phenomenon is observed in an array of
      protein structures in oligomeric conformation. Protein structures in swapped
      conformations perform diverse functional roles and are also associated with
      deposition diseases in humans. We have performed in-depth literature curation and
      structural bioinformatics analyses to develop an integrated knowledgebase of
      proteins involved in 3D domain swapping. The hallmark of 3D domain swapping is
      the presence of distinct structural segments such as the hinge and swapped
      regions. We have curated the literature to delineate the boundaries of these
      regions. In addition, we have defined several new concepts like 'secondary major
      interface' to represent the interface properties arising as a result of 3D domain
      swapping, and a new quantitative measure for the 'extent of swapping' in
      structures. The catalog of proteins reported in 3DSwap knowledgebase has been
      generated using an integrated structural bioinformatics workflow of database
      searches, literature curation, by structure visualization and sequence-structure
      function analyses. The current version of the 3DSwap knowledgebase reports 293
      protein structures, the analysis of such a compendium of protein structures will
      further the understanding molecular factors driving 3D domain swapping.

PMID- 21959868
TI  - Tripal: a construction toolkit for online genome databases.
AB  - As the availability, affordability and magnitude of genomics and genetics
      research increases so does the need to provide online access to resulting data
      and analyses. Availability of a tailored online database is the desire for many
      investigators or research communities; however, managing the Information
      Technology infrastructure needed to create such a database can be an undesired
      distraction from primary research or potentially cost prohibitive. Tripal
      provides simplified site development by merging the power of Drupal, a popular
      web Content Management System with that of Chado, a community-derived database
      schema for storage of genomic, genetic and other related biological data. Tripal
      provides an interface that extends the content management features of Drupal to
      the data housed in Chado. Furthermore, Tripal provides a web-based Chado
      installer, genomic data loaders, web-based editing of data for organisms, genomic
      features, biological libraries, controlled vocabularies and stock collections.
      Also available are Tripal extensions that support loading and visualizations of
      NCBI BLAST, InterPro, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology
      analyses, as well as an extension that provides integration of Tripal with
      GBrowse, a popular GMOD tool. An Application Programming Interface is available
      to allow creation of custom extensions by site developers, and the look-and-feel
      of the site is completely customizable through Drupal-based PHP template files.
      Addition of non-biological content and user-management is afforded through
      Drupal. Tripal is an open source and freely available software package found at
      http://tripal.sourceforge.net.

PMID- 21959869
TI  - Early endosomal rerouting of major histocompatibility class I conformers.
AB  - Major histocompatibility class I (MHC-I) molecules are present at the cell
      surface both as fully conformed trimolecular complexes composed of heavy chain
      (HC), beta-2-microglobulin (beta2m) and peptide, and various open forms, devoid
      of peptide and/or beta2m (open MHC-I conformers). Fully conformed MHC-I complexes
      and open MHC-I conformers can be distinguished by well characterized monoclonal
      antibody reagents that recognize their conformational difference in the
      extracellular domain. In the present study, we used these tools in order to test
      whether conformational difference in the extracellular domain determines
      endocytic and endosomal route of plasma membrane (PM) proteins. We analyzed PM
      localization, internalization, endosomal trafficking, and recycling of human and
      murine MHC-I proteins on various cell lines. We have shown that fully conformed
      MHC-I and open MHC-I conformers segregate at the PM and during endosomal
      trafficking resulting in the exclusion of open MHC-I conformers from the
      recycling route. This segregation is associated with their partitioning into the
      membranes of different compositions. As a result, the open MHC-I conformers
      internalized with higher rate than fully conformed counterparts. Thus, our data
      suggest the existence of conformation-based protein sorting mechanism in the
      endosomal system.

PMID- 21959870
TI  - Randomised, phase III trial of epoetin-beta to treat chemotherapy-induced anaemia
      according to the EU regulation.
AB  - BACKGROUND: Erythropoietin-stimulating agents (ESAs) effectively decrease the
      transfusion requirements of patients with chemotherapy-induced anaemia (CIA).
      Recent studies indicate that ESAs increase mortality and accelerate tumour
      progression. The studies also identify a 1.6-fold increased risk of venous
      thromboembolism. The ESA labelling was thus revised in Europe and the United
      States in 2008. This is the first randomised, phase III trial evaluating the
      efficacy and safety of epoetin-beta (EPO), an ESA, dosed in accordance with the
      revised labelling, which specifies that ESAs should be administered to CIA
      patients with a haemoglobin level of <= 10 g dl-1 and that a sustained
      haemoglobin level of > 12 g dl-1 should be avoided. METHODS: A total of 186 CIA
      patients (8.0 g dl-1 <= haemoglobin <= 10.0 g dl-1) with lung or gynaecological
      cancer were randomised to receive EPO 36,000 IU or placebo weekly for 12 weeks.
      RESULTS: The proportion of patients receiving transfusions or with haemoglobin <
      8.0 g dl-1 between week 5 and the end of the treatment period as the primary end
      point was significantly lower in the EPO group (n=89) than in the placebo group
      (n=92; 10.0% vs 56.4%, P < 0.001). The proportion receiving transfusions was
      significantly lower in the EPO group (4.5% vs 19.6%, P=0.002). Changes in quality
      of life were not different. No significant differences in adverse events - for
      example, the incidence of thromboembolic events was 1.1% for each group - or the
      1-year overall survival were observed between groups. CONCLUSION: Weekly EPO
      administered according to the revised labelling approved by the European
      Medicines Agency is effective and well tolerated for CIA treatment. Further
      investigations are needed on the effect of ESAs on mortality.

PMID- 21959871
TI  - Cost-effectiveness analysis of trastuzumab to treat HER2-positive advanced
      gastric cancer based on the randomised ToGA trial.
AB  - BACKGROUND: We performed a cost-effectiveness analysis of trastuzumab plus
      chemotherapy for human epidermal growth factor type-2 (HER2)-positive advanced
      gastric cancer (GC) based on data obtained from the Trastuzumab for Gastric
      Cancer (ToGA) trial from a Japanese perspective. METHODS: The following Japanese
      and Korean populations of the ToGA trial were analysed to obtain mean overall and
      progression-free survival times: (1) all HER2-positive populations, (2)
      immunohistochemical (IHC) 2+/fluorescence in situ hybridisation (FISH)+ or IHC 3+
      populations, and (3) IHC 3+ only population. The effect of trastuzumab treatment
      on mean survival time was estimated by fitting a Weibull parametric function.
      Costs were calculated from the perspective of health-care payer. Neither costs
      nor outcomes were discounted because of short life expectancy. RESULTS: In the
      base-case analysis, the incremental cost-effectiveness ratio was (1) JPY 12
      million (?110,000) per quality-adjusted life year (QALY) gained and JPY 8.9
      million (?81,000) per life-year gained (LYG) for all HER2-positive populations,
      (2) JPY 9.1 million (?83,000) per QALY gained and JPY 6.6 million (?60,000) per
      LYG for the IHC 2+/FISH+ or IHC 3+ population, and (3) JPY 6.1 million (?55,000)
      per QALY gained and JPY 4.3 million (?39,000) per LYG for the IHC 3+ population.
      CONCLUSION: Trastuzumab treatment for IHC 3+ populations is cost effective. Our
      analysis can find a cost-effective subgroup when advanced GC is treated by
      trastuzumab.

PMID- 21959872
TI  - "Tinni" rice (Oryza rufipogon Griff.) production: an integrated sociocultural
      agroecosystem in eastern Uttar Pradesh of India.
AB  - This study reports how Traditional Ecological Knowledge (TEK) and informal
      cultural institutions have conserved key varieties of the wildgrowing rice,
      'tinni' (red rice, or brownbeard rice, Oriza rufipogon Griff.), within the Bhar
      community of eastern Uttar Pradesh, India. The study was conducted, using
      conventional and participatory methods, in 10 purposively selected Bhar villages.
      Two distinct varieties of tinni ('tinni patali' and 'tinni moti') with differing
      habitats and phenotypic characters were identified. Seven microecosystems (Kari,
      Badaila, Chammo, Karmol, Bhainsiki, Bhainsala and Khodailia) were found to
      support these varieties in differing proportions. Tinni rice can withstand more
      extreme weather conditions (the highest as well as lowest temperatures and
      rainfall regimes) than the 'genetically improved' varieties of rice (Oriza sativa
      L.) grown in the region. Both tinni varieties are important bioresources for the
      Bhar's subsistence livelihoods, and they use distinctive conservation approaches
      in their maintenance. Bhar women are the main custodians of tinni rice
      agrobiodiversity, conserving tinni through an institution called Sajha.
      Democratic decision-making at meetings organized by village elders determines the
      market price of the tinni varieties. Overall, the indigenous institutions and
      women's participation seem to have provided safeguards from excessive
      exploitation of tinni rice varieties. The maintenance of tinni through cultural
      knowledge and institutions serves as an example of the importance of locally
      maintained crop varieties in contributing to people's resilience and food
      security in times of rapid social and environmental change.

PMID- 21959873
TI  - T2-weighted cardiac MR assessment of the myocardial area-at-risk and salvage area
      in acute reperfused myocardial infarction: comparison of state-of-the-art dark
      blood and bright blood T2-weighted sequences.
AB  - PURPOSE: To compare different state-of-the-art T2-weighted (T2w) imaging
      sequences combined with late gadolinium enhancement (LGE) for myocardial salvage
      area (MSA) assessment by cardiac magnetic resonance (CMR). T2w imaging has been
      used to assess the myocardial area at risk (AAR) in acute myocardial infarction
      (AMI) patients, but its clinical application is challenging due to technical and
      physical limitations. MATERIALS AND METHODS: Thirty patients with reperfused AMI
      underwent complete CMR imaging 2-5 days after hospital admission. Myocardial AAR
      and MSA were quantified on four different T2w sequences: (a) free-breathing T2
      prepared single-shot balanced steady-state free precession (T2p_ssbSSFP); (b)
      breathhold T2-weighted acquisition for cardiac unified T2 edema (ACUTE); (c)
      breathhold T2w dark-blood inversion recovery turbo-spin echo (IR-TSE) (short-term
      inversion recovery: STIR); and (d) free-breathing high-resolution T2 dark-blood
      navigated BLADE. The diagnostic performance of each technique was also assessed.
      RESULTS: Quantitative analysis showed significant differences in myocardial AAR
      extent as quantified by the four T2w sequences (P < 0.05). There were also
      significant differences in sensitivity, specificity and overall diagnostic
      performance. CONCLUSION: Detection and quantification of AAR, and thus of MSA, by
      T2wCMR in reperfused AMI patients varied significantly between different T2w
      sequences in the same clinical setting.

PMID- 21959874
TI  - Comparison of fluoroscopy time during coronary angiography and interventions by
      radial and femoral routes- can we decrease the fluoroscopy time with increased
      experience? An observational study.
AB  - OBJECTIVE: Radial route of access is increasingly being used for coronary
      angiograms and intervention. However, radiation exposure of operators was not
      known in our set up with either transfemoral or transradial procedures. The
      objective of the study was to compare related peripheral arterial route radiation
      exposure of operators by assessing fluoroscopy time. The secondary objective was
      to determine the relationship of operator experience with fluoroscopy time.
      METHODS: This observational study was conducted in a tertiary care center -
      Cardiovascular Institute of Karachi (Pakistan) during the period of July 1(st)
      2009 to September 30(th) 2009. We studied 1016 consecutive adult patients
      referred for coronary angiography (CA) or percutaneous coronary intervention
      (PCI). Patients who underwent right heart catheterization or for valvuloplasty
      were excluded from the study. Out of these 1016 patients, 928 were diagnostic CAs
      (734 via femoral route [f-CA] and 194 via radial route [r-CA]) and 88 were PCI
      (64 via femoral route [f-PCI] and 24 via radial route [r-PCI]). Fluoroscopy time
      was recorded as a surrogate of radiation exposure. Statistical analysis was
      performed using unpaired t, Mann-Whitney U, Chi-square and ANOVA tests. RESULTS:
      Mean fluoroscopy time was found to be significantly higher in patients who
      underwent r-CA (6.3+/-3.8 vs 4.0+/-2.9 min; p<0.001) and r-PCI (15.1+/-11.8 vs
      10.3+/-7.4 min; p=0.02) as compared with those underwent f-CA and f-PCI. Mean
      fluoroscopy time of well experienced operators was also high in r-CAs (5.4+/-2.9
      vs 4.2+/-3.5 min; p=0.004). CONCLUSION: Radial procedures are associated with
      longer fluoroscopy time that may result in high radiation exposure to radial
      operators. Even well experienced radial operators cannot minimize their
      fluoroscopy time to the level of well experienced femoral operators.

PMID- 21959875
TI  - The role of nebivolol in the prevention of contrast-induced nephropathy in
      patients with renal dysfunction.
AB  - OBJECTIVE: This prospective study was designed to evaluate the potential
      protective effect of nebivolol compared with metoprolol on the development of
      contrast-induced nephropathy (CIN) following coronary angiography in patients
      with renal dysfunction. METHODS: Ninety patients with stable coronary angina
      pectoris with renal insufficiency (creatinine value >=1.2 mg/dl) were included
      for this prospective study. Patients were divided into two groups. Patients in
      group 1 (n=55) received oral administration of nebivolol 5 mg/daily for coronary
      artery disease and/or hypertension. Group 2 consisted of 35 patients who received
      metoprolol 50 mg/daily for the same indications. All patients were hydrated with
      0.9% NaCl at a rate of 1 mL/kg/hr for 12 hours before and 24 hours after the
      procedure. Patients were also given N-acetylcysteine (NAC) 600 mg twice a day,
      beginning 24 hours before and continuing 48 hours after the procedure. All
      patients underwent routine coronary angiography. Serum creatinine was assessed
      just before, immediately after and 48 hours after the procedure. CIN was defined
      as an increase in serum creatinine concentration of >=25% within 48 hours after
      the procedure compared to the patient's baseline value. Tests for significance
      between groups were conducted using the independent sample t-test for continuous
      variables and Chi-square test for categorical variables. RESULTS: Baseline serum
      creatinine levels were statistically comparable in two groups. Following
      angiography, serum creatinine levels increased in both groups. Post-angiographic
      creatinine levels were not statistically different in the nebivolol and the
      metoprolol groups. Contrast induced nephropathy developed in 13 patients (24%) of
      the nebivolol group and in 12 patients (33%) of the metoprolol group. The
      incidence of CIN was statistically significantly lower in the nebivolol group
      comparing with the metoprolol group (p=0.03). CONCLUSION: The use of oral
      nebivolol for one week at a dose of 5 mg per day may decrease the incidence of
      contrast-induced nephropathy in patients who underwent coronary angiography with
      renal dysfunction. The small numbers of this study do not allow to draw final
      conclusion on the use of nebivolol in the prevention of CIN. Therefore, larger
      studies may be necessary to address the definite role of nebivolol in this
      setting.

PMID- 21959876
TI  - The role of nebivolol in the prevention of contrast-induced nephropathy.

PMID- 21959877
TI  - [Evaluation of factors affecting healthy life style behaviors and quality of life
      in patients with heart disease].
AB  - OBJECTIVE: The aim of this cross-sectional study was to determine
      sociodemographic and disease related factors affecting the quality of life and
      life style behavior in patients with heart disease. METHODS: Data are collected
      via information form, Healthy Life Style Behaviors Scale, and short form-36 life
      quality scale to 325 people with heart disease. T test for independent samples,
      one-way ANOVA and Pearson correlation analyzes are used in statistical evaluation
      of the data. RESULTS: It has been determined that average age was 56.98+/-11.89
      years, 58.2% were male, 48.6% were graduated from primary school, 30.2% were
      haven't got any additional diseases of the patients in this study. Point average
      of healthy life style behaviors of people with heart disease obtained as 127.45+/
      20.51 and physical main dimension mean score was 51.95+/-22.21, mental main
      dimension mean score was 52.71+/-19.48. It has been understood that, in general,
      that male patients in 49-60 age group and married, having bachelor and master
      degrees, in good socio-economic status, working, without any additional disease
      and took training related to their disease, received high point from healthy life
      style behavior scale, but patients with cardiac failure had lower points
      (p<0.05). There was a positive relation between life qualities and healthy life
      style behaviors of the patients (p<0.01). CONCLUSION: Increasing of life quality
      of the patients especially with cardiac failure will be ensured by executing
      studies on development of healthy life style behaviors for people with heart
      disease and arranging training programs to them related to their disease.

PMID- 21959878
TI  - Evaluation of diagnostic accuracy of portable echocardiography in newborns.
AB  - OBJECTIVE: Congenital heart disease is the most common life-threatening anomaly
      in the neonatal period. Screening for this disease with portable echocardiography
      is crucial to diagnose in the early period, and it has benefits in saving time
      and decreasing the cost. Portable echocardiography has advantages of rapid access
      and lower costs and also has advantage that in intensive care units there is no
      necessity to move patients. With these advantages, it is aimed to compare the
      sensitivity of portable echocardiography comparing to standard echocardiography.
      METHODS: In this study, the portable echocardiography results of the sequentially
      enrolled newborns hospitalized in the neonatal departments are revised. Portable
      echocardiography results were verified with standard echocardiography in 83 (43%)
      female and 111 (57%) male patients. This study was planned as a study on
      diagnostic accuracy. RESULTS: The gestational periods were between 24 weeks, 3
      days and 42 weeks (average 35 weeks+/-4 weeks 3 days). Birth weights were between
      500 and 4850 grams (average 2370+/-936 grams). The reason that portable
      echocardiography had been studied was murmur in 113 (58.2%) patients, cyanosis in
      47 (24.2%) patients, prenatal anomaly in 12 (6.2%) patients, bradycardia in 12
      (6.2%) patients, maternal diabetes in 6 (3.1%) patients and respiratory distress
      in 4 (2.1%) patients. Out of 194 patients 8 (4.1%) had differences between
      standard and portable echocardiography. Compared to standard echocardiography,
      portable echocardiography has the sensitivity values ranged between 99.3-100% and
      the specificity values ranged between 90.9-100% in diagnosis of specific CHD
      anomalies. Positive predictive value was between 50-100% whereas negative
      predictive value was between 97.9-100%. The agreement between results of two
      tests was determined as very good - kappa 0.886, 95%CI -0.821-0.951, p<0.0001.
      CONCLUSION: It is demonstrated that portable echocardiography has a high
      sensitivity especially diagnosing major heart defects, and with advantages of
      rapid access and lower costs it is estimated that increasing usage of portable
      echocardiography could be beneficial.

PMID- 21959879
TI  - Factors associated with left atrial size in obese children: an observational
      study.
AB  - OBJECTIVE: Left atrial size can be considered an independent risk factor for
      cardiovascular diseases. The measurements of left atrium may be used to assess
      obesity, which is an important risk factor of cardiovascular diseases. It is
      aimed to determine the factors that effect to the left atrial size, which is an
      indicator of cardiac risk in obese children without hypertension. METHODS: The
      cross-sectional observational study was performed between April 2008 and
      September 2009 at the clinic of Pediatric Cardiology. Eighty obese and 82 lean
      children were studied. Diagnosis of obesity was defined according to the World
      Health Organization classification as the standard deviation score of body mass
      index being over + 2 standard deviation of the same gender and age. All subjects
      underwent two-dimensional, M-mode, and Doppler echocardiographic studies.
      Student's t-test, Chi-square test, Pearson correlation analysis, and multiple
      stepwise regression analyses were used to compare the subjects, differences in
      group proportions, evaluate the relation of variables with the left atrial size,
      and examine the effects of significant independent variables, respectively.
      RESULTS: The mean age of obese patients was 11.7+/-2.2 years and it of lean
      subjects was 11.7+/-2.2 years. Body weight, body mass index, standard deviation
      score of body mass index, waist circumference, systolic and diastolic blood
      pressure, fasting insulin, and insulin resistance statistically increased in
      obese children (p<0.05). The left atrial size statistically correlated (p<0.05)
      with age (r=0.523), body mass index (r=0.394), waist circumference (r=0.421),
      diastolic blood pressure (r=0.230), insulin resistance (r=0.350), and left
      ventricular mass (r=0.535). It was determined that age (beta=0.491; 95% CI=0.091
      0.892; p=0.001) and left ventricular mass (beta=0.055; 95% CI=0.026-0.085;
      p=0.017) were the most effective independent factors associated with left atrial
      size among other independent factors in multiple regression analysis. CONCLUSION:
      We found that left atrial size was mostly influenced by age and left ventricular
      mass in obese children. Therefore, it is important that left atrial size is
      follow up in childhood obesity.

PMID- 21959880
TI  - The outcome of the vertical vein left intact during the surgery  for total
      anomalous venous connection and its effects on ventricular functions.
AB  - OBJECTIVE: We examined the fate of intact vertical vein during long-term follow
      up and its effects on ventricular functions. METHODS: Eighty one patients with
      all types of total anomalous pulmonary venous connection (TAPVC) were operated.
      Thirty-one patients with supracardiac type TAPVC were examined in our
      retrospective cohort study. Groups were evaluated with respect to left ventricle
      area, volume, end-systolic, end diastolic diameter, early and late term mortality
      and properties of pulmonary hypertensive crisis. Vertical vein was left open in
      14 patients and it was ligated in 17 patients. Wilcoxon rank and Mann- Whitney U
      tests were used to compare variables between groups. RESULTS: After mean follow
      up of 48+/-36 months, vertical vein closed spontaneously in 3 patients. Two of
      them were closed surgically due to elevated shunt flow and there was spontaneous
      closure in one patient who had the highest pulmonary artery pressure amongst
      others postoperatively. Preoperative left ventricular area, volume, end-systolic
      diameter and end-diastolic diameter values of the patients increased from 3.5+/-
      0.9 mm(2)-2.9+/-0.9 mm(3)-14+/-5 mm-8+/-4.5 mm to 8+/-3.3 mm(2)-16+/-8.7 mm(3)
      27+/-6.7 mm-17+/-4.8 mm at the postoperative period in Group 1, and from 6.8+/
      3.5 mm(2)-8.4+/-8.7 mm(3)-15+/-6.4 mm-9+/-5.3 mm to 7.4+/-5.2 mm(2)-16+/-1.7
      mm(3)-21.7+/-5 mm-13.5+/-4.1 mm in Group 2, respectively (p=0.02, p=0.039,
      p=0.054, and p=0.07, respectively). CONCLUSION: Vertical vein remains intact in
      most of the patients and may be closed spontaneously in patients with elevated
      pulmonary resistance. Intact vertical vein both decompresses the left ventricular
      cavity in patients with decreased left ventricular compliance until the
      ventricular muscle adapts to new workload and improves ventricular functions on
      long term follow up. Therefore, we conclude that vertical vein should be left
      open in selected patients.

PMID- 21959881
TI  - Cardiovascular involvement in patients with systemic sclerosis: insights from
      electromechanical characteristics of the heart.
AB  - Systemic sclerosis is a severe, life threatening autoimmune disease involving the
      skin and visceral organs, including the lungs, gastrointestinal tract, kidneys
      and heart. Cardiac involvement in systemic sclerosis, which is an important
      mortality predictor may involve myocardium, conduction system, vascular wall,
      pericardium, pulmonary vessels causing pulmonary hypertension. Thus, the
      detection of cardiac involvement is necessary in systemic sclerosis. With the
      more widespread use of novel non-invasive imaging techniques, the cardiac
      involvement is more frequently encountered in daily practice. Noninvasive
      evaluation can offer an advantage in early prediction of poor prognosis and give
      a chance to apply new therapeutic approaches for cardiac involvement. In this
      review, we intend to present cardiac involvement of systemic sclerosis and
      clinical diagnostic modalities, including electromechanical properties of the
      atrium and ventricles, for assessment this involvement.

PMID- 21959882
TI  - [MRI based volumetric assessment of knee cartilage after ACL-reconstruction,
      correlated with qualitative morphologic changes in the joint and with clinical
      outcome. Is there evidence for early posttraumatic degeneration?].
AB  - PURPOSE: The purpose of this study was to analyze potential quantitative and
      qualitative changes of the knee cartilage and joint indicative of early
      posttraumatic OA 4 years after ACL-reconstruction and to correlate the MRI
      findings with the clinical outcome (CO). MATERIALS AND METHODS: 1.5 T MRI-scans
      were performed on 9 patients post-op and 4 years later. Using a high-resolution T
      1-w-fs-FLASH-3D-sequence cartilage volume (cVol) and thickness (mTh) were
      quantified. Using standard PD-w fs and T 1-w sequences qualitative changes of the
      joint structures were analyzed based on the WORMS-score. CO was rated by an
      orthopaedic surgeon using Lysholm-score, OAK-score, Tegner-activity-score (TAS),
      and Arthrometer KT-1000 testing. RESULTS: Mean changes of cVol were -1.8 %
      (range: -5.9 %; + 0.7 %) and of mTh -0.8 % (range: -3.0 %; + 1.1 %). No
      significant change (95 %-CI) could be identified for any compartment. Three
      patients developed new peripatellar ostheophytes, acute trauma related changes
      mostly decreased. Mean outcome of Lysholm-score and OAK-score were 90 pts and 86
      pts, mean TAS was 4.3 pts. Average maximum tibial translation reached 5.2 mm
      comparing to 6.7 mm on the healthy contralateral side. CONCLUSION: Despite a
      tendency towards decreased cVol and mTh 4 years after ACL-reconstruction qMRI
      revealed no significant cartilage loss. Newly developing osteophytes did not
      match with the observed good CO. This small pilot study motivates future
      quantitative and qualitative-structural MRI-based assessment of articular
      cartilage and other joint structures in order to improve diagnostic tools for the
      detection of early OA.

PMID- 21959883
TI  - [Diagnostic accuracy of contrast-enhanced 64-row MSCT coronary angiography in
      patients with severe coronary calcification in the clinical routine].
AB  - PURPOSE: Our aim was to evaluate the diagnostic accuracy of contrast-enhanced 64
      MSCT coronary angiography (MSCT-CA) in patients with severe coronary
      calcification. MATERIALS AND METHODS: 110 patients with an Agatston score > 400
      were included in this retrospective analysis. Each patient underwent both
      conventional coronary angiography and MSCT-CA. No patient was excluded from the
      study because of coronary artery bypass grafting or coronary stenting. The
      results of MSCT-CA were compared with those of conventional coronary angiography
      and the diagnostic accuracy for detecting a hemodynamically significant stenosis
      was determined for coronary segments, vessels and patients. RESULTS: The average
      Agatston score for the study population was 1368 +/- 1105. At least one
      significant stenosis was detected in 97 patients (88%) during conventional
      coronary angiography defining the gold standard. The sensitivity, specificity,
      positive and negative predictive values of MSCT-CA for detecting a significant
      stenosis were 54%, 83%, 52% and 85% for coronary segments (n = 1384), 80%, 70%,
      74% and 77% for coronary vessels (n = 440), and 100%, 31%, 92% and 100% for
      patients (n = 110), respectively. No significant correlation could be observed
      between the degree of coronary calcification and the number of misclassified
      coronary segments. CONCLUSION: Artifacts caused by severe coronary calcification
      decrease the diagnostic accuracy of MSCT-CA. Performing MSCT-CA in patients with
      an Agatston score > 400 with the drawbacks of contrast media application and
      radiation exposure should be critically questioned and this decision should be
      made on an individual basis.

PMID- 21959884
TI  - [Ganglioglioma of the conus medullaris].

PMID- 21959885
TI  - Mirror therapy in lower limb amputees--a look beyond primary motor cortex
      reorganization.
AB  - PURPOSE: Phantom pain in upper limb amputees is associated with the extent of
      reorganization in the primary sensorimotor cortex. Mirror visual feedback therapy
      has been shown to improve phantom pain. We investigated the extent of cortical
      reorganization in lower limb amputees and changes in neural activity induced by
      mirror therapy. MATERIALS AND METHODS: Eight lower limb amputees underwent 12
      sessions of MVFT and functional magnetic resonance imaging (fMRI) of the brain
      before the first and after the last MVFT session. FMRI sessions consisted of two
      runs in which subjects were instructed to perform repetitive movement of the
      healthy and phantom ankle. RESULTS: Before MVFT, the mean phantom pain intensity
      was 4.6 +/- 3.1 on a visual analog scale and decreased to 1.8 +/- 1.7 (p = 0.04).
      We did not observe a consistent pattern of cortical activation in primary
      sensorimotor areas during phantom limb movements. Following MVFT, increased
      activity was obtained in the right orbitofrontal cortex during phantom ankle
      movements. Comparison of cortical activity during movements of the phantom ankle
      and the intact ankle showed significantly higher activity in the left inferior
      frontal cortex (pars triangularis). CONCLUSION: These results question the known
      association between phantom pain and primary sensorimotor reorganization and
      propose reorganizational changes involving multiple cortical areas in lower limb
      amputees. Finally, reduction of phantom pain after mirror visual feedback therapy
      was associated with increased prefrontal cortical activity during phantom ankle
      movements.

PMID- 21959886
TI  - Right ventricular involvement in patients with Fabry's disease and the effect of
      enzyme replacement therapy.
AB  - PURPOSE: According to echocardiography reports, Fabry cardiomyopathy not only
      affects the left ventricle (LV) but also the right ventricle (RV). Until now no
      MRI studies about the effect of enzyme replacement therapy (ERT) on the RV are
      available. We evaluated the effect of ERT on the RV. MATERIALS AND METHODS: In
      this prospective trial 14 patients with genetically proven Fabry's disease were
      examined using a 1.5 T MR scanner before ERT and after 13 +/- 1 months of ERT.
      All patients underwent cardiac MR imaging and the RV/LV cardiac morphology and
      function were analyzed. RESULTS: At baseline examination the values were as
      follows: RV mass 31 +/- 6 g/m (2), end-diastolic volume (EDV) 88 +/- 13 ml/m (2),
      end-systolic volume (ESV) 39 +/- 9 ml/m (2), stroke volume (SV) 49 +/- 7 ml/m (2)
      and ejection fraction (EF) 56 +/- 5 %. The RV mass and EDV decreased
      significantly after 13 +/- 1 months on ERT (mass 27 +/- 7 g/m (2), p < 0.05, EDV
      76 +/- 24 ml/m (2), p < 0.05), with no significant change of ESV (33 +/- 13 ml/m
      (2)), SV (43 +/- 12 ml/m (2)) and EF (57 +/- 7 %). The LV mass (102 +/- 26 g/m
      (2) vs. 94 +/- 27 g/m (2), p < 0.05), EDV (76 +/- 13 ml/m (2) vs. 66 +/- 22 ml/m
      (2), p < 0.05) and ESV (29 +/- 9 ml/m (2) vs. 23 +/- 9 ml/m (2), p < 0.05)
      decreased significantly while the EF (64 +/- 7 % vs. 66 +/- 5 %; p < 0.05)
      increased significantly. CONCLUSION: Besides the known beneficial effect on the
      LV, ERT improves RV mass and EDV.

PMID- 21959887
TI  - Radioembolization of hepatic tumors: flow redistribution after the occlusion of
      intrahepatic arteries.
AB  - PURPOSE: Radioembolization using 90yttrium is an emerging therapy option for
      unresectable liver malignancies. In order to reduce the number of yttrium
      injections, endovascular occlusion of a segmental hepatic artery has been
      proposed. The aim of this study was to assess whether sufficient vascular
      redistribution of the occluded liver segments through intrahepatic collaterals
      can be observed. MATERIALS AND METHODS: 27 patients with hepatocellular carcinoma
      (n = 16) or hepatic metastases (n = 11) were studied. Hepatic angiography was
      performed on average 16 days prior to radioembolization. The segment II/III
      artery (n = 9) or the segment IV artery (n = 18) was occluded using coils.
      Technectium-99m-labeled macroaggregated albumin (99mTc-MAA) was injected into the
      right and the remaining part of the left hepatic artery in order to identify any
      hepatic volume not included in the perfused area. Patients underwent a SPECT/CT
      on average 1 h after the 99mTc-MAA injection. Two radiologists evaluated the
      SPECT/CT scans regarding the presence of non-perfused hepatic segments.
      Furthermore, hepatic perfusion was assessed by digital subtraction angiography
      (DSA) on the day of radioembolization. RESULTS: In 16/27 patients (59%) a
      perfusion of the occluded liver segment was visible on the SPECT/CT scan. In 8/11
      patients without flow redistribution at the time of the SPECT/CT, perfusion of
      the occluded segment through hepatic collaterals was observed during angiography
      prior to radioembolization. Hence, flow redistribution was eventually found in
      24/27 patients (89%). CONCLUSION: Flow redistribution after the occlusion of
      intrahepatic arteries prior to radioembolization can be successfully induced in
      the majority of patients with anatomical variants of the hepatic arteries.

PMID- 21959888
TI  - [Gynecomastia in methotrexate treatment in Churg-Strauss syndrome].

PMID- 21959889
TI  - A discussion of molecular biology methods for protein engineering.
AB  - A number of molecular biology techniques are available to generate variants from
      a particular start gene for eventual protein expression. We discuss the basic
      principles of these methods in a repertoire that may be used to achieve the
      elemental steps in protein engineering. These include site-directed, deletion and
      insertion mutagenesis. We provide detailed case studies, drawn from our own
      experiences, packaged together with conceptual discussions and include an
      analysis of the techniques presented with regards to their uses in protein
      engineering.

PMID- 21959890
TI  - Downregulation of hepatic cytochrome P450 3A in mice infected with Babesia
      microti.
AB  - To investigate effects of Babesia infection on drug metabolism, we
      intraperitoneally inoculated B. microti into ICR mice and measured the expression
      and activity of hepatic cytochrome P450 (CYP) 3A, a major drug-metabolizing
      enzyme. Twelve days after infection, CYP3A11 mRNA, CYP3A protein and activity and
      mRNAs of nuclear receptors, which participate in CYP3A expression, were
      significantly reduced. These results suggest that B. microti infection suppresses
      CYP3A-dependent drug metabolism. Additionally, tumor necrosis factor (TNF)-alpha
      and nitric oxide synthase (NOS) 2 mRNAs were induced in the infected mouse liver.
      Since TNF-alpha is one of the potent mediators that induce NOS2 and repress CYP3A
      transcription, the possible involvement of TNF-alpha in this downregulation of
      CYP3A was discussed.

PMID- 21959891
TI  - Maternal exposure to low doses of DES altered mRNA expression of hepatic
      microsomal enzymes in male rat offspring.
AB  - Our previous studies demonstrated that prenatal diethylstilbestrol (DES)
      treatment disrupts steroidogenesis but induces high-level expression of androgen
      receptor (AR) mRNA to inhibit the disruption of spermatogenesis. This study
      examined which prenatal DES treatment influenced hepatic microsomal enzymes,
      CYP3A1, CYP2B1/2, CYP2C11, UGT2B1 (UDP-glucuronosyltransferase 2B1), and IGF-1
      (insulin-like growth factor-1), in male rat offspring. DES treatment decreased
      the mRNA expression levels of CYP3A1 and CYP2B1/2, but did not alter the
      expression of CYP2C11. At 6 weeks, DES treatment increasd the mRNA expression
      levels of UGT2B1 and IGF-1. These results suggest that prenatal DES treatment
      alters two hepatic enzymes (CYP3A1 and CYP2B1/2) and IGF-1 mRNA expression levels
      to counteract the low level of testosterone, but this disrupted UGT2B1 mRNA
      expression reduces the testosterone level.

PMID- 21959892
TI  - Comparison of two quantitative assays for xenotropic murine leukemia virus
      related virus.
AB  - Xenotropic murine leukemia virus-related virus (XMRV), a novel gammaretrovirus in
      humans, was found in patients with prostate cancer (PC) and chronic fatigue
      syndrome (CFS). However, there has been controversy whether XMRV is directly
      associated with human diseases. In this study, we developed a LacZ marker rescue
      assay using human embryonic kidney 293T cells and a focus assay using a feline
      fibroblastic sarcoma-positive leukemia-negative QN10S cells. XMRV induced
      prominent foci in QN10S cells and the viral titer determined by the focus assay
      was as high as that by the LacZ marker rescue assay. Because the focus assay is
      simple and sensitive, it will be useful for monitoring infectious XMRVs in CFS
      and PC patients and virological studies for XMRV.

PMID- 21959893
TI  - Influence of factors during superovulation on embryo production in Korean
      Holstein cattle.
AB  - The aim of this study was to investigate the influence of key parameters (donor
      parity, milk production, post-parturient day, season and milk recording data)
      associated with efficiency of embryo recovery (ER) in Holstein cattle. Elite
      Holstein cows and heifers were selected for ER, while Holstein heifers were used
      as recipients. The numbers of transferable embryos (TEs) produced were not
      significantly different when analyzed in terms of donor parity, milk production,
      postparturient day and season. However, the numbers of TEs were significantly
      increased when the milk protein (%; P)/fat (%; F) ratio was over 0.95 and/or the
      milk urea nitrogen (MUN) was between 12 and 18 dl/ml. The results from ET showed
      no differences in pregnancy rates among Holstein heifers receiving other types,
      developmental stage codes and quality grades of embryos. The mean interval from
      ER to artificial insemination was 60.6 days. Moreover, 19 offspring that had milk
      recording data showed a similar milk yield performance to that of the donor cows.
      In conclusion, this study showed that in Holstein cows, embryos were recovered
      and transferred and resulted in production of viable calves. Furthermore, P/F
      ratio and MUN could be candidate indicators for selection of high-efficiency
      donor cows.

PMID- 21959894
TI  - A case of congenital hyperostosis in a newborn piglet.
AB  - One female newborn piglet showed prominent thickening of both forelimbs and died
      soon after birth. Histopathologically, thin and woven trabeculae of bone was
      extending out from the edge of cortical bone in the affected forelimbs, and
      diagnosed as congenital hyperostosis. The extent of radially proliferated
      trabeculae was most prominent in radioulna. Many round- to spindle-shaped cells
      were observed in periosteum, which were considered to be osteoblasts. Around the
      periosteum, the mesenchymal proliferation was extensive with abundant mucus, and
      cartilaginous metaplastic changes were observed mainly around the radioulna and
      humerus. Dilatation of vessels with fibrin deposition in vessel walls was often
      observed, which were considered to reflect the localized circulatory disturbance.

PMID- 21959895
TI  - Prevalence of Lawsonia intracellularis, Salmonella spp. and Eimeria spp. in
      healthy and diarrheic pet rabbits.
AB  - A total of 170 fresh fecal samples (healthy; n=137, diarrheic; n=33) were
      collected from pet rabbits. By using PCR and formol-ether concentration method, a
      total 13/137 healthy rabbit feces were positive for L. intracellularis, 6/137 for
      Salmonella, and 13/137 for Eimeria. On the other hand, a total 17/33 diarrheic
      rabbit fecal samples were positive for L. intracellularis, 10/33 for Salmonella,
      and 21/33 for Eimeria. From these results, more than 20% of clinically normal and
      97% of diarrheic rabbits were positive for single or concurrent infection of
      three pathogens. To the best of our knowledge, this is the first report to
      describe the prevalence of the microorganisms L. intracellularis, Salmonella and
      Eimeria in pet rabbits.

PMID- 21959896
TI  - Hepatic hilar transection method for liver surgery (with video).
AB  - The procedure used to isolate the hepatic artery, the portal vein and the bile
      duct separately at the hepatic hilum was first reported in the 1940s, and remains
      significant as an essential technique for liver surgery in the era of more
      complicated liver surgery and liver transplantation. The anatomy of the vessels
      at the hepatic hilum is highly variable; therefore, preoperative imaging studies
      are indispensable for understanding the anatomy in each individual patient. The
      minimal extent of the transection should be defined according to the operative
      procedure, as excessive disruption of the blood flow and lymphatic vessels can
      induce postoperative complications. When isolating the vessels, gentle handling
      and appropriate ligation/division of the vessels are required to avoid bleeding
      and injuries to the vessels to be preserved. The bile duct is wrapped with
      perivascular connective tissue and is difficult to isolate separately. Therefore,
      the hilar plate should be divided together with the bile duct, under the guidance
      of intraoperative cholangiography.

PMID- 21959897
TI  - Sectionectomy of the liver.
AB  - Anatomic resection of the liver, which refers to the systemic elimination of the
      main tumor with micrometastases, preserves liver function and is highly
      recommended. Tumors located centrally or in the vicinity of major portal pedicles
      or hepatic veins, however, tend to require extensive hepatectomy. Anatomic
      sectionectomy of the liver might represent an alternative to such extensive
      resection. Preoperative simulation, external landmarks, selective
      devascularization, and intraoperative ultrasound are useful to achieve anatomic
      sectionectomy. Anatomic resection requires division of the relevant portal vein,
      hepatic artery, and bile duct. This may be achieved by individual isolation of
      the three elements or by mass isolation of all three in their surrounding fibrous
      sheath (Glisson's capsule). Both approaches are equally effective for extensive
      resections. When sectionectomy is performed, however, the isolation of individual
      vasculobiliary elements is sometimes difficult and dangerous compared with the
      isolation of the sectional portal pedicles. By identifying the portal pedicles to
      individual anatomic sections, it is possible to control the inflow to the section
      that is intended for resection. Anatomic sectionectomy is a safe alternative to
      extensive liver resection in selected patients, avoiding unnecessary sacrifice of
      functional liver parenchyma and increasing the opportunity to perform repeat
      resections in cases of recurrence.

PMID- 21959898
TI  - Neutron powder diffraction investigation on the crystal and magnetic structure of
      (Ho(0.50+x)Ca(0.50-x))(Mn(1-x)Cr(x))O3.
AB  - The crystal and magnetic structure of (Ho(0.50+x)Ca(0.50-x))(Mn(1-x)Cr(x))O(3) (x
      = 0.00, 0.01, 0.02, 0.03) has been investigated between 5 and 300 K by means of
      neutron powder diffraction followed by Rietveld refinement and dc magnetic
      measurements. During cooling an orthorhombic to monoclinic phase transition
      occurs on account of the charge and orbital ordering taking place in the Mn sub
      lattice; at low temperature phase separation takes place and the main monoclinic
      phase coexists with a secondary orthorhombic phase, whose amount slightly
      increases with the increase of Cr content. Cr(3+) is not involved in orbital
      ordering or superexchange interactions. The charge and magnetic ordering are
      decoupled: the Mn moments order according to a CE-type structure in all samples.

PMID- 21959899
TI  - Ortho-methylated tribenzotriquinacenes--paving the way to curved carbon networks.
AB  - The synthesis of sterically crowded tribenzotriquinacenes with complete and
      partial methylation of the ortho-positions has been achieved using the double
      cyclodehydration strategy. This leads to a twisted tribenzotriquinacene core and
      enables further functionalization for the future synthesis of curved model
      compounds for defective carbon networks.

PMID- 21959900
TI  - Perisynaptic aggrecan-based extracellular matrix coats in the human lateral
      geniculate body devoid of perineuronal nets.
AB  - The extracellular matrix surrounds different neuronal compartments in the mature
      nervous system. In a variety of vertebrates, most brain regions are loaded with a
      distinct type of extracellular matrix around the somatodendritic part of neurons,
      termed perineuronal nets. The present study reports that chondrotin sulfate
      proteoglycan-based matrix is structured differently in the human lateral
      geniculate body. Using various chondrotin sulfate proteoglycan-based
      extracellular matrix antibodies, we show that perisomatic matrix labeling is
      rather weak or absent, whereas dendrites are contacted by axonal coats appearing
      as small, oval structures. Confocal laser scanning microscopy and electron
      microscopy demonstrated that these typical structures are associated with
      synaptic loci on dendrites. Using multiple labelings, we show that different
      chondrotin sulfate proteoglycan components of the extracellular matrix do not
      associate exclusively with neuronal structures but possibly associate with glial
      structures as well. Finally, we confirm and extend previous findings in primates
      that intensity differences of various extracellular matrix markers between magno-
      and parvocellular layers reflect functional segregation between these layers in
      the human lateral geniculate body.

PMID- 21959901
TI  - Obscure gastrointestinal bleeding: single centre experience of capsule endoscopy.
AB  - The advent of capsule endoscopy (CE) has resulted in a paradigm shift in the
      approach to the diagnosis and management of patients with obscure
      gastrointestinal bleeding (OGIB). With increasing global availability of this
      diagnostic tool, it has now become an integral part of the diagnostic algorithm
      for OGIB in most parts of the world. However, there is scant data on optimum
      timing of CE for maximizing diagnostic yield. OGIB continues to be a challenge
      because of delay in diagnosis and consequent morbidity and mortality. We
      evaluated the diagnostic yield of CE in identifying the source of bleeding in
      patients with OGIB. We identified patients who underwent CE at our institution
      from May 2006 to May 2011. The patients' medical records were reviewed to
      determine the type of OGIB (occult, overt), CE results and complications, and
      timing of CE with respect to onset of bleeding. Out of 346 patients investigated
      for OGIB, 246 (71.1%) had some lesion detected by CE. In 206 patients (59.5%),
      definite lesions were detected that could unequivocally explain the OGIB. Small
      bowel angiodysplasia, ulcer/erosions secondary to Crohn's disease, non-steroidal
      anti-inflammatory agent use, and neoplasms were the commonest lesions detected.
      Visualization of the entire small bowel was achieved in 311 (89.9%) of cases.
      Capsule retention was noted in five patients (1.4%). In this study, CE was proven
      to be a safe, comfortable, and effective, with a high rate of accuracy for
      diagnosing OGIB. 

PMID- 21959902
TI  - The presence of nuclear families in prehistoric collective burials revisited: the
      bronze age burial of Montanissell Cave (Spain) in the light of aDNA.
AB  - Ancient populations have commonly been thought to have lived in small groups
      where extreme endogamy was the norm. To contribute to this debate, a genetic
      analysis has been carried out on a collective burial with eight primary
      inhumations from Montanissell Cave in the Catalan pre-Pyrenees. Radiocarbon
      dating clearly placed the burial in the Bronze Age, around 3200 BP. The
      composition of the group-two adults (one male, one female), one young woman, and
      five children from both sexes-seemed to represent the structure of a typical
      nuclear family. The genetic evidence proves this assumption to be wrong. In fact,
      at least five out of the eight mitochondrial haplotypes were different, denying
      the possibility of a common maternal ancestor for all of them. Nevertheless, 50%
      of the inhumations shared haplogroup J, so the possibility of a maternal
      relationship cannot be ruled out. Actually, combining different analyses
      performed using ancient and living populations, the probability of having four
      related J individuals in Montanissell Cave would range from 0.9884 to 0.9999.
      Owing to the particularities of this singular collective burial (small number of
      bodies placed altogether in a hidden cave, the evidence of non-simultaneous
      interments, close dating and unusual grave goods), we suggest that it might
      represent a small group with a patrilocal mating system.

PMID- 21959903
TI  - Gradient porous materials by emulsion centrifugation.
AB  - Oil-in-water emulsions are centrifuged to generate a gradient distribution of
      emulsion droplets. This structure is locked by freezing or polymerization and the
      subsequent removal of the solvents produces gradient porous materials.

PMID- 21959904
TI  - Growth hormone in pediatric intestinal failure patients: small patients,
      significant insights.

PMID- 21959905
TI  - Mapping and validation of quantitative trait loci associated with wheat yellow
      mosaic bymovirus resistance in bread wheat.
AB  - Wheat yellow mosaic (WYM) caused by wheat yellow mosaic bymovirus (WYMV) has been
      growing as one of the most serious diseases affecting wheat production in China.
      In this study, the association of quantitative trait loci (QTLs) governing WYMV
      resistance with molecular markers was established using 164 recombinant inbred
      lines (RILs) derived from 'Xifeng Wheat' (highly resistant) * 'Zhen 9523' (highly
      susceptible). Phenotypic data of WYMV resistance of the RILs were collected from
      4-year, two-location replicated field trials. A molecular marker-based linkage
      map, which was comprised of 273 non-redundant loci and represented all the 21
      wheat chromosomes, was constructed with the JoinMap 4.0 software. Using the
      Windows QTL Cartographer V2.5 software, three QTLs associated with WYMV
      resistance, QYm.njau-3B.1, QYm.njau-5A.1 and QYm.njau-7B.1, were detected on
      chromosomes 3BS, 5AL, and 7BS, respectively. The favorable allele effects were
      all contributed by 'Xifeng Wheat'. Among the three QTLs, QYm.njau-3B.1 and
      QYm.njau-5A.1 were detected in all the four trials and the overall mean, and
      could explain 3.3-10.2% and 25.9-53.7% of the phenotypic variation, respectively,
      while QYm.njau-7B.1 was detected in one trial and the overall mean and explained
      4.9 and 3.3% of the phenotypic variation, respectively. A large portion of the
      variability for WYMV response was explained by a major QTL, QYm.njau-5A.1. The
      relationship of the molecular markers linked with QYm.njau-5A.1 and the WYMV
      resistance was further validated using a secondary F(2) population. The results
      showed that three markers, i.e., Xwmc415.1, CINAU152, and CINAU153, were closely
      linked to QYm.njau-5A.1 with the genetic distances of 0.0, 0.0, and 0.1 cM,
      respectively, indicating they should be useful in marker-assisted selection (MAS)
      wheat breeding for WYMV resistance. A panel of germplasm collection consisting of
      46 wheat varieties with known WYMV response phenotypes was further used to
      validate the presence and effects of QYm.njau-5A.1 and the above three markers.
      It was found that QYm.njau-5A.1 was present in 12 of the 34 WYMV-resistant
      varieties.

PMID- 21959906
TI  - Identification of genetic factors controlling kernel hardness and related traits
      in a recombinant inbred population derived from a soft * 'extra-soft' wheat
      (Triticum aestivum L.) cross.
AB  - Kernel hardness or texture, used to classify wheat (Triticum aestivum L.) into
      soft and hard classes, is a major determinant of milling and baking quality.
      Wheat genotypes in the soft class that are termed 'extra-soft' (with kernel
      hardness in the lower end of the spectrum) have been associated with superior end
      use quality. In order to better understand the relationship between kernel
      hardness, milling yield, and various agronomic traits, we performed quantitative
      trait mapping using a recombinant inbred line population derived from a cross
      between a common soft wheat line and a genotype classified as an 'extra-soft'
      line. A total of 47 significant quantitative trait loci (QTL) (LOD >= 3.0) were
      identified for nine traits with the number of QTL affecting each trait ranging
      from three to nine. The percentage of phenotypic variance explained by these QTL
      ranged from 3.7 to 50.3%. Six QTL associated with kernel hardness and break flour
      yield were detected on chromosomes 1BS, 4BS, 5BS, 2DS, 4DS, and 5DL. The two most
      important QTL were mapped onto orthologous regions on chromosomes 4DS (Xbarc1118
      Rht-D1) and 4BS (Xwmc617-Rht-B1). These results indicated that the 'extra-soft'
      characteristic was not controlled by the Hardness (Ha) locus on chromosome 5DS.
      QTL for eight agronomic traits occupied two genomic regions near semi-dwarf genes
      Rht-D1 on chromosome 4DS and Rht-B1 on chromosome 4BS. The clustering of these
      QTL is either due to the pleiotropic effects of single genes or tight linkage of
      genes controlling these various traits.

PMID- 21959907
TI  - Inheritance and molecular characterization of broad range tolerance to herbicides
      targeting acetohydroxyacid synthase in sunflower.
AB  - Ahasl1 is a multilallelic locus where all the induced and natural mutations for
      herbicide tolerance were described thus far in sunflower (Helianthus annuus L.).
      The allele Ahasl1-1 confers moderate tolerance to imidazolinone (IMI), Ahasl1-2,
      and Ahasl1-3 provides high levels of tolerance solely to sulfonylurea (SU) and
      IMI, respectively. An Argentinean wild sunflower population showing plants with
      high level of tolerance to either an IMI and a SU herbicide was discovered and
      used to develop an inbred line designated RW-B. The objectives of this work were
      to determine the relative level and pattern of cross-tolerance to different AHAS
      inhibiting herbicides, the mode of inheritance, and the molecular basis of
      herbicide tolerance in this line. Slight or no symptoms observed after
      application of different herbicides indicated that RW-B possesses a completely
      new pattern of tolerance to AHAS-inhibiting herbicides in sunflower. Biomass
      response to increasing doses of metsulfuron or imazapyr demonstrated a higher
      level of tolerance in RW-B with respect to Ahasl1-1/Ahasl1-1 and Ahasl1-2/Ahasl1
      2 lines. On the basis of genetic analyses and cosegregation test, it was
      concluded that tolerance to imazapyr in the original population is inherited as a
      single, partially dominant nuclear gene and that this gene is controlling the
      tolerance to four different AHAS-inhibiting herbicides. Pseudo-allelism test
      permitted us to conclude that the tolerant allele present in RW-B is an allelic
      variant of Ahasl1-1 and was designated as Ahasl1-4. Nucleotide and deduced amino
      acid sequence indicated that the Ahasl1-4 allele sequence of RW-B has a leucine
      codon (TTG) at position 574 (relative to the Arabidopsis thaliana AHAS sequence),
      whereas the enzyme from susceptible lines has a tryptophan residue (TGG) at this
      position. The utilization of this new allele in the framework of weed control and
      crop rotation is discussed.

PMID- 21959908
TI  - Molecular analysis of glycinin genes in soybean mutants for development of gene
      specific markers.
AB  - Soybean mutant lines that differ in 11S glycinin and 7S beta-conglycinin seed
      storage protein subunit compositions were developed. These proteins have
      significant influence on tofu quality. The molecular mechanisms underlying the
      mutant lines are unknown. In this study, gene-specific markers for five of the
      glycinin genes (Gy1 to Gy5) were developed using three 11S null lines, two A(4)
      null Japanese cultivars, Enrei and Raiden, and a control cultivar, Harovinton.
      Whereas gene-specific primers produced the appropriate products in the control
      cultivar for the Gy1, Gy2, Gy3 and Gy5 genes, they did not amplify in mutants
      missing the A(1a)B(2), A(2)B(1a), A(1b) B(1b), and A(3)B(4) subunits. However,
      ecotype targeting induced local lesions in genomes (EcoTILLING) and sequencing
      analysis revealed that the absence of the A(4) peptide in the mutants is due to
      the same point mutation as that in Enrei and Raiden. Selection efficiency of the
      gene-specific primer pairs was tested using a number of breeding lines
      segregating for the different subunits. Primer pairs specific to each of the Gy1,
      Gy2, Gy3, and Gy5 genes can be used to detect the presence or absence of
      amplification in normal or mutant lines. The Gy4 null allele can be selected for
      by temperature-switch PCR (TS-PCR) for identification of the A(4) (G4) null
      genotypes. In comparison to protein analysis by SDS-PAGE, gene-specific markers
      are easier, faster and more accurate for analysis, they do not have to use seed,
      and can be analyzed at any plant growth stage for marker-assisted selection.

PMID- 21959909
TI  - High resolution mapping of Dense spike-ar (dsp.ar) to the genetic centromere of
      barley chromosome 7H.
AB  - Spike density in barley is under the control of several major genes, as
      documented previously by genetic analysis of a number of morphological mutants.
      One such class of mutants affects the rachis internode length leading to dense or
      compact spikes and the underlying genes were designated dense spike (dsp). We
      previously delimited two introgressed genomic segments on chromosome 3H (21 SNP
      loci, 35.5 cM) and 7H (17 SNP loci, 20.34 cM) in BW265, a BC(7)F(3) nearly
      isogenic line (NIL) of cv. Bowman as potentially containing the dense spike
      mutant locus dsp.ar, by genotyping 1,536 single nucleotide polymorphism (SNP)
      markers in both BW265 and its recurrent parent. Here, the gene was allocated by
      high-resolution bi-parental mapping to a 0.37 cM interval between markers SC57808
      (Hv_SPL14)-CAPSK06413 residing on the short and long arm at the genetic
      centromere of chromosome 7H, respectively. This region putatively contains more
      than 800 genes as deduced by comparison with the collinear regions of barley,
      rice, sorghum and Brachypodium, Classical map-based isolation of the gene dsp.ar
      thus will be complicated due to the infavorable relationship of genetic to
      physical distances at the target locus.

PMID- 21959910
TI  - Plantar vibrotactile detection deficits in adults with chronic ankle instability.
AB  - PURPOSE: The purpose of this study was to investigate the vibrotactile detection
      thresholds of the plantar cutaneous afferents in subjects with chronic ankle
      instability compared with healthy control subjects. METHODS: Eight adults with
      chronic ankle instability and eight adults with no ankle sprain history
      participated. Vibrotactile detection thresholds were assessed using a mechanical
      stimulus generator system, mounted onto an articulated microscope arm, which
      delivered sinusoidal vibrotactile inputs to the foot sole at three different
      sites: head of the first metatarsal, base of the fifth metatarsal, and the heel.
      Vibrotactile stimulation was delivered at a range of test frequencies that
      corresponded to the known responsiveness of cutaneous mechanoreceptors in the
      glabrous skin of the foot sole (10, 25, and 50 Hz). Probe displacement measures
      (dB) from the last eight displacement trials that contained 50% positive
      detection responses were averaged to obtain a single threshold estimate for each
      test frequency and site combination. RESULTS: The results of this study indicate
      that no significant group-by-site interactions were found for any test
      frequencies (P > 0.29). However, group main effects were present at the 10-Hz (P
      < 0.0001), 25-Hz (P = 0.03), and 50-Hz (P = 0.04) test frequencies, indicating
      that subjects with chronic ankle instability had significantly higher detection
      thresholds or less sensitivity when stimulation sites were pooled. CONCLUSIONS:
      The results of this study indicate that subjects with chronic ankle instability
      may demonstrate decreased sensitivity on the plantar surface of the foot. These
      alterations in plantar cutaneous somatosensation may help explain the underlying
      mechanisms associated with the prolonged sensorimotor system impairments in
      postural control and gait commonly exhibited by people with chronic ankle
      instability.

PMID- 21959911
TI  - Novel C-H...C contacts involving 3,5-dimethylpyrazole ligands in a
      tetracoordinate Co(II) complex.
AB  - A violet-blue cobalt(II) complex [Co(4-nbz)(2)(DMP)(2)] (1), where 4-nbz = 4
      nitrobenzoate and DMP = 3,5-dimethylpyrazole, has been prepared at room
      temperature. Crystallographic studies on 1.0.5H(2)O reveal that the molecules of
      1 are linked by a variety of non-covalent bonds including a novel type of C-H...C
      contact forming, with assistance from N-H...O, C-H...O and C-H...pi interactions,
      an intricate 3-D supramolecular network. Theoretical calculations suggest that
      the observed C-H...C interactions are energetically quite significant.

PMID- 21959912
TI  - Automated tracking in live-cell time-lapse movies.
AB  - The development of high-throughput live cell imaging is currently limited by the
      capabilities of image analysis. Software is required to generate single cell time
      courses from large data sets of time-lapse movies and to follow properties of
      individual cells. Automated cell tracking faces notorious problems associated
      with cell division, high cell density and cell mobility. In particular, a large
      number of cell traces are discarded in experiments with extended observation
      times due to image analysis ambiguities. Here we develop an algorithm for robust
      tracking based on cost matrices from multiple cell parameters such as object
      size, position or texture. Singularities in cost indicate tracking conflicts,
      which can be categorized into event classes such as cell division, lysis or
      overlap of cells. We demonstrate that multiple parameter tracking (MPT) generates
      single cell fluorescence time traces more reliably than algorithms based on
      position tracking only. Context-sensitive automatic evaluation and event
      management increase the yield of continuous and correctly assigned time traces by
      27%.

PMID- 21959913
TI  - Reduced coupling of water molecules near the surface of reverse micelles.
AB  - We report on vibrational dynamics of water near the surface of AOT reverse
      micelles studied by narrow-band excitation, mid-IR pump-probe spectroscopy.
      Evidence of OH-stretch frequency splitting into the symmetric and asymmetric
      modes is clearly observed for the interfacial H(2)O molecules. The polarization
      memory of interfacial waters is preserved over an exceptionally extended >10 ps
      timescale which is a factor of 100 longer than in bulk water. These observations
      point towards negligibly small intermolecular vibrational coupling between the
      water molecules as well as strongly reduced water rotational mobility within the
      interfacial water layer.

PMID- 21959914
TI  - Psychiatry under National Socialism: remembrance and responsibility.

PMID- 21959915
TI  - Sensitivity to changes during antidepressant treatment: a comparison of
      unidimensional subscales of the Inventory of Depressive Symptomatology (IDS-C)
      and the Hamilton Depression Rating Scale (HAMD) in patients with mild major,
      minor or subsyndromal depression.
AB  - In the efficacy evaluation of antidepressant treatments, the total score of the
      Hamilton Depression Rating Scale (HAMD) is still regarded as the 'gold standard'.
      We previously had shown that the Inventory of Depressive Symptomatology (IDS) was
      more sensitive to detect depressive symptom changes than the HAMD17 (Helmreich et
      al. 2011). Furthermore, studies suggest that the unidimensional subscales of the
      HAMD, which capture the core depressive symptoms, outperform the full HAMD
      regarding the detection of antidepressant treatment effects. The aim of the
      present study was to compare several unidimensional subscales of the HAMD and the
      IDS regarding their sensitivity to changes in depression symptoms in a sample of
      patients with mild major, minor or subsyndromal depression (MIND). Biweekly IDS
      C28 and HAMD17 data from 287 patients of a 10-week randomised, placebo-controlled
      trial comparing the effectiveness of sertraline and cognitive-behavioural group
      therapy in patients with MIND were converted to subscale scores and analysed
      during the antidepressant treatment course. We investigated sensitivity to
      depressive change for all scales from assessment-to-assessment, in relation to
      depression severity level and placebo-verum differences. The subscales performed
      similarly during the treatment course, with slight advantages for some subscales
      in detecting treatment effects depending on the treatment modality and on the
      items included. Most changes in depressive symptomatology were detected by the
      IDS short scale, but regarding the effect sizes, it performed worse than most
      subscales. Unidimensional subscales are a time- and cost-saving option in judging
      drug therapy outcomes, especially in antidepressant treatment efficacy studies.
      However, subscales do not cover all facets of depression (e.g. atypical symptoms,
      sleep disturbances), which might be important for comprehensively understanding
      the nature of the disease depression. Therefore, the cost-to-benefit ratio must
      be carefully assessed in the decision for using unidimensional subscales.

PMID- 21959916
TI  - Neural correlates of the attention network test in schizophrenia.
AB  - Attentional deficits are prominent in schizophrenia, affecting nearly all
      cognitive functions. Human attention comprises three essential components:
      alerting, orienting and executive control. For the assessment of these functions,
      the attention network test (ANT) has been proposed and used in healthy controls
      and patients. In schizophrenia, the ANT has revealed behavioral deficits;
      however, the corresponding neural correlates have not been examined. In the
      present study, neural correlates of attention were investigated in 17
      schizophrenia patients and 17 healthy controls using the ANT with fMRI.
      Behavioral deficits emerged in the alertness system with a reduced efficiency for
      temporal cues. In fMRI, changes were observed for all three domains-alerting,
      orienting and conflict-and revealed hyper- as well as hypoactivation in patients.
      Affected regions during alerting comprised a broad fronto-temporo-parieto
      occipito-cerebellar network, while differences during orienting mainly tapped
      fronto-parietal regions and during conflict processing a thalamo-frontal-temporal
      occipital network including the postcentral regions. In general, hyperactivations
      were positively correlated with more severe psychopathologial symptoms.

PMID- 21959923
TI  - Association of ARMS2/HTRA1 variants with polypoidal choroidal vasculopathy
      phenotype in a Korean population.
AB  - PURPOSE: To investigate whether ARMS2 (rs10490924)/HTRA1 (rs11200638) variants
      are associated with polypoidal choroidal vasculopathy (PCV) in a Korean
      population and with various PCV phenotypes. METHODS: A case-control study
      comprised of 103 patients with PCV and 112 control subjects. The PCV and control
      groups were genotyped for ARMS2 (rs10490924) and HTRA1 (rs11200638)
      polymorphisms. Clinical characteristics were evaluated, including best-corrected
      visual acuity (BCVA), fundus findings, and angiographic findings, at first visit.
      RESULTS: Two single nucleotide polymorphisms generated highly significant allelic
      associations with PCV. The frequency of vitreous hemorrhage (VH) was different
      among the genotypes with respect to both rs10490924 and rs11200638. The frequency
      of the T allele of rs10490924 was higher in PCV patients with VH than in PCV
      patients without VH. The frequency of the A allele of rs11200638 was higher in
      PCV patients with VH than in PCV patients without VH. In rs10490924, the mean
      BCVA of the GG genotype group was better than that of the TT and TG genotype
      groups. In rs11200638, the mean BCVA of the GG genotype group was better than
      that of the AA and AG genotype groups. CONCLUSIONS: The ARMS2 (rs10490924)/HTRA1
      (rs11200638) variants are significantly associated with the risk of PCV in a
      Korean population. ARMS2/HTRA1 variants contribute significantly to the PCV
      phenotypes, including frequency of VH and mean BCVA at baseline.

PMID- 21959924
TI  - Prioritizing maternal and child health in independent South Sudan.
AB  - With its independence secured on 9th July 2011, the Republic of South Sudan faces
      a daunting task to improve public health and primary care in one of the poorest
      countries in the world. Very high maternal and child mortality rates must be a
      major concern for the new national government and for the many international
      agencies working in the country. Poor maternal health outcomes are primarily due
      to poor prenatal, delivery and post natal care services in health facilities,
      coupled with low literacy, widespread poverty, and poor nutrition among the
      general population. Child mortality is the result of widespread malnutrition,
      pneumonia, malaria, vaccine preventable diseases and diarrheal diseases. National
      responses to HIV and AIDS with international assistance have been encouraging
      with relatively low rates of infection. This paper explores barriers and
      identifies opportunities available to work toward achieving the targets for
      Millennium Development Goals (MDGs) 5 and 4 to reduce maternal mortality from its
      current rate of 2,054 deaths per 100,000 live births, and child mortality
      (currently 135 deaths per 1,000 live births) respectively in the new nation.
      National and international organizations have a social responsibility to mobilize
      efforts to focus on maternal, child health and nutrition issues targeting the
      worst affected regions for improving access to primary care and obstetrical
      services. Initiatives are needed to build up community access to primary care
      with a well supervised community health workers program, as well as training mid
      level management capacity with higher levels of funding from national and
      international sources to promote public health than current in the new republic.

PMID- 21959925
TI  - Pre-pregnancy predictors of diabetes in pregnancy among Aboriginal and Torres
      Strait Islander women in North Queensland, Australia.
AB  - To identify pre-pregnancy risk factors for diabetes in pregnancy among a cohort
      of Australian Indigenous women. Data on 1,009 Indigenous women of childbearing
      age who participated in a 1998-2000 health screening program in far north
      Queensland were linked to Queensland hospitalisations data. Women who attended
      hospital after their health check for a pregnancy-related condition were
      identified. The data on women who were hospitalised for birth were also linked to
      Queensland perinatal data. Of 220 women who gave birth, 23 had diabetes in the
      pregnancy following their health check. A strong predictor of having a subsequent
      pregnancy affected by diabetes was suboptimal glucose control before conception.
      The presence of the metabolic syndrome predicted over a threefold increase in
      risk among non-diabetic women after adjustment for age and ethnicity (PR, 3.50;
      95% CI, 1.54-8.00). For each 1-cm increase in waist circumference, there was an
      age-adjusted increase in risk of 4% for diabetes in pregnancy (1.04; 1.01-1.06).
      For each 1-mmHg increase in blood pressure (systolic and diastolic), there was an
      age-adjusted increase in risk of 3% (1.03; 1.01-1.05 and 1.03; 1.00-1.07,
      respectively). Associations between hypercholesterolaemia and dyslipidaemia and
      diabetes in the subsequent pregnancy were diminished after adjustment for age and
      ethnicity. The risk for women with "hyper-triglyceridaemic waist" phenotype
      before pregnancy was diminished by adjustment for age, ethnicity and baseline
      fasting glucose. Alcohol intake, smoking, level of physical activity and red cell
      folate showed little effect. Identification of women at particularly high risk
      for future diabetes in pregnancy, given their pre-pregnancy health, is important
      so that they can manage their risks and where overweight or obesity is a factor,
      interventions aimed at weight management should be implemented.

PMID- 21959926
TI  - Cardiac motion in diffusion-weighted MRI of the liver: artifact and a method of
      correction.
AB  - PURPOSE: To characterize cardiac motion artifacts in the liver and assess the use
      of a postprocessing method to mitigate these artifacts in repeat measurements.
      MATERIALS AND METHODS: Three subjects underwent breathhold diffusion-weighted
      (DW) scans consisting of 25 repetitions for three b-values (0, 500, 1000
      sec/mm(2)). Statistical maps computed from these repetitions were used to assess
      the distribution and behavior of cardiac motion artifacts in the liver. An
      objective postprocessing method to reduce the artifacts was compared with
      radiologist-defined gold standards. RESULTS: Signal dropout is pronounced in
      areas proximal to the heart, such as the left lobe, but also present in the right
      lobe and in distal liver segments. The dropout worsens with b-value and leads to
      overestimation of the diffusivity. By reference to a radiologist-defined gold
      standard, a postprocessing correction method is shown to reduce cardiac motion
      artifact. CONCLUSION: Cardiac motion leads to significant artifacts in liver DW
      imaging; we propose a postprocessing method that may be used to mitigate the
      artifact and is advantageous to standard signal averaging in acquisitions with
      multiple repetitions.

PMID- 21959927
TI  - Endothelin-1 promotes MMP-13 production and migration in human chondrosarcoma
      cells through FAK/PI3K/Akt/mTOR pathways.
AB  - Tumor malignancy is associated with several cellular properties including
      proliferation and ability to metastasize. Endothelin-1 (ET-1) the most potent
      vasoconstrictor plays a crucial role in migration and metastasis of human cancer
      cells. We found that treatment of human chondrosarcoma (JJ012 cells) with ET-1
      increased migration and expression of matrix metalloproteinase (MMP)-13. ET-1
      mediated cell migration and MMP-13 expression were reduced by pretreatment with
      inhibitors of focal adhesion kinase (FAK), phosphatidylinositol 3-kinase (PI3K),
      Akt, and mammalian target of rapamycin (mTOR), as well as the NF-kappaB inhibitor
      and the IkappaB protease inhibitor. In addition, ET-1 treatment induced
      phosphorylation of FAK, PI3K, AKT, and mTOR, and resulted in increased NF-kappaB
      luciferase activity that was inhibited by a specific inhibitor of PI3K, Akt,
      mTOR, and NF-kappaB cascades. Taken together, these results suggest that ET-1
      activated FAK/PI3K/AKT/mTOR, which in turn activated IKKalpha/beta and NF-kappaB,
      resulting in increased MMP-13 expression and migration in human chondrosarcoma
      cells.

PMID- 21959928
TI  - Virus-templated synthesis of ZnO nanostructures and formation of field-effect
      transistors.

PMID- 21959929
TI  - Value of visual inspection, bimanual palpation, and intraoperative
      ultrasonography during hepatic resection for liver metastases of colorectal
      carcinoma.
AB  - BACKGROUND: Intraoperative detection of new nodules is common in patients
      undergoing hepatectomy for colorectal liver metastases, although the value of
      intraoperative diagnosis is not well assessed. METHODS: A prospectively collected
      and recorded database was retrospectively analyzed. Helical computed tomography
      (CT) results were correlated with those of the intraoperative diagnosis in 183
      consecutive patients undergoing 254 consecutive hepatectomies, including repeated
      resection for colorectal liver metastases. RESULTS: In total, 270 nodules were
      newly detected during 65 hepatectomies. The sensitivity of CT to detect
      metastatic nodules was 72.8% (722/992), but it decreased to 34.6% (125/361) for
      small (<= 1 cm diameter) tumors. Intraoperative visual inspection and/or
      palpation detected 207 of 270 nodules. Intraoperative ultrasonography (IOUS)
      played an important role in identifying deep (>= 1 cm from the surface) and
      comparatively small (<= 1 cm diameter) nodules (4/9 vs. 16/18, respectively, for
      those >1 cm vs. <= 1 cm diameter). The likelihood of intraoperative detection of
      new nodules increased from 10 in 112 to 6 in 9 when the preoperative tumor number
      increased from solitary to >= 10, resulting in an overall likelihood of 65 in 254
      (25.6%). Of 65 patients with new nodules, 21 had at least one nodule that was
      detected only by IOUS. Preoperatively scheduled hepatectomy was altered in 47
      (72%) patients, although additional limited resection(s) were sufficient to
      remove these nodules in 43 (91%) of them. CONCLUSIONS: Visual inspection,
      palpation, and IOUS had equally indispensable roles in detecting new nodules
      during hepatectomy. Detection was common and usually necessitated alteration,
      albeit moderately, of the surgical plan.

PMID- 21959930
TI  - Laparoscopic intersphincteric resection for low rectal cancer.
AB  - BACKGROUND: Laparoscopic intersphincteric resection (ISR) after neoadjuvant
      chemoradiation is helpful in the management of patients with low rectal cancer.
      With the advent of this technique, the need for performance of abdominoperineal
      resection seems to have decreased in patients with very low rectal tumors. The
      aim of the present study was to evaluate the feasibility, the functional outcome,
      and the short-term oncologic outcomes of laparoscopic ISR for low rectal
      adenocarcinoma at our institution. METHODS: We retrospectively reviewed the data
      of 111 consecutive patients who underwent laparoscopic ISR for low rectal
      adenocarcinoma between July 2005 and December 2009. Demographic status, surgical
      outcomes, functional outcome data, and oncologic outcome data were collected.
      RESULTS: The mean distance of the tumor from the anal verge was 3.4 cm (range: 1
      5 cm). The mean operative time was 214.7 min (range, 150-450 min). The mean
      distal resection margin was 1.3 +/- 1.1 cm. Morbidity occurred in 24 patients
      (21.6%), including anastomotic leakage in 2 patients (1.8%). The mean Wexner
      continence score after stoma repair was 7.5 +/- 2.7 (range: 2 ~ 19), and 9.8 in
      total ISR, 7.3 in partial ISR (P = 0.071). The 3-year overall survival rate was
      92.8%, and the 3-year disease-free survival rate was 73.0%. Local recurrence was
      noted in 6 of the 111 patients with TNM stage I to III (5.4%). The patients with
      lesions at 2 cm to the dentate line had a 7.07-fold greater risk of local
      recurrence, including a 13.42-fold greater risk of lateral pelvic wall recurrence
      and perineal recurrence (95% Confidence interval [CI], 1.141-158.006; P = 0.009)
      than in those who had lesions more than 2 cm from the anal verge (95% CI, 1.290
      38.832; P = 0.011). CONCLUSIONS: Laparoscopic ISR after neoadjuvant
      chemoradiation can be recommended as a technically feasible, minimally invasive,
      and a sphincter-saving procedure with acceptable functional and short-term
      oncologic outcomes in patients with very low rectal cancer.

PMID- 21959931
TI  - The impact of heavy smoking on anastomotic leakage and stricture after low
      anterior resection in rectal cancer patients.
AB  - BACKGROUND: Anastomotic complications after low anterior resection are associated
      with perianastomotic ischemia. Smoking is one of the main causes of microvascular
      disease that is correlated with tissue ischemia. The purpose of the present study
      was to assess the impact of smoking on anastomotic complications after low
      anterior resection in rectal cancer patients. METHODS: Between January 2005 and
      December 2008, 412 patients underwent low anterior resection for rectal cancers
      by a single surgeon at Seoul National University Hospital. Excluded from this
      series were 197 patients with postoperative radiation therapy, cancers that were
      located above 10 cm from the anal verge, or lack of medical records, and the
      remaining 215 patients were included for analysis. Significant variables in the
      univariate analysis were subsequently subject to multivariate analysis for
      identification of risk factors for complications. RESULTS: The rate of
      anastomotic complications was 10.7% (23 of 215 patients). Univariate analysis
      showed that male gender, body mass index higher than 25 kg/m(2), smoking history,
      smoking amount, type of operation, and presence of a protective stoma were
      associated with anastomotic complications. In multivariate analysis, a history of
      heavy smoking was a significant risk factor for anastomotic complications.
      CONCLUSIONS: A history of heavy smoking (more than 40 pack-years) is an
      independently significant risk factor for anastomotic complications after low
      anterior resection in rectal cancer patients.

PMID- 21959932
TI  - Elevation of liver function tests after laparoscopic gastrectomy using a
      Nathanson liver retractor.
AB  - BACKGROUND: Although pneumoperitoneum has been suspected as a possible cause of
      transient elevation of liver function tests (LFTs) after laparoscopic surgery,
      liver damage by direct retraction could also influence postoperative LFTs. The
      aim of this study was to clarify whether laparoscopic gastrectomy (LG) using a
      Nathanson retractor was associated with the postoperative elevation of LFTs
      compared with open gastrectomy (OG). METHODS: A retrospective cohort study of 199
      LG and 120 OG patients was conducted. Serum aspartate aminotransferase (AST),
      alanine aminotransferase (ALT), and total bilirubin were measured before
      operation and at postoperative days 1, 3, and 7. Abnormal elevation of LFTs was
      defined as a grade 2 or greater elevation in any parameter. To assess the
      possible effect of pneumoperitoneum, patients who underwent laparoscopic (n =
      324) and open (n = 56) colectomy for colorectal cancer were also compared.
      RESULTS: In both LG and OG groups, LFTs were significantly elevated
      postoperatively compared with baseline values. Mean ALT and total bilirubin
      levels on days 1, 3, and 7 were significantly higher in the LG than OG group.
      Abnormal elevation of LFTs was more frequent in the LG than OG group (50 vs.
      12%). In multivariate analysis, LG was significantly associated with
      postoperative liver dysfunction (odds ratio [OR] = 7.99; 95% confidence interval
      [95% CI] = 3.69-18.85). No significant difference in the elevation of the LFTs
      was observed between laparoscopic and open colectomy (6% and 9%, respectively).
      CONCLUSIONS: LG resulted in frequent elevation of LFTs. Care should be taken to
      minimize intraoperative liver damage when performing LG using a Nathanson
      retractor.

PMID- 21959933
TI  - Fas death receptor signalling: roles of Bid and XIAP.
AB  - Fas (also called CD95 or APO-1), a member of a subgroup of the tumour necrosis
      factor receptor superfamily that contain an intracellular death domain, can
      initiate apoptosis signalling and has a critical role in the regulation of the
      immune system. Fas-induced apoptosis requires recruitment and activation of the
      initiator caspase, caspase-8 (in humans also caspase-10), within the death
      inducing signalling complex. In so-called type 1 cells, proteolytic activation of
      effector caspases (-3 and -7) by caspase-8 suffices for efficient apoptosis
      induction. In so-called type 2 cells, however, killing requires amplification of
      the caspase cascade. This can be achieved through caspase-8-mediated proteolytic
      activation of the pro-apoptotic Bcl-2 homology domain (BH)3-only protein BH3
      interacting domain death agonist (Bid), which then causes mitochondrial outer
      membrane permeabilisation. This in turn leads to mitochondrial release of
      apoptogenic proteins, such as cytochrome c and, pertinent for Fas death receptor
      (DR)-induced apoptosis, Smac/DIABLO (second mitochondria-derived activator of
      caspase/direct IAP binding protein with low Pi), an antagonist of X-linked
      inhibitor of apoptosis (XIAP), which imposes a brake on effector caspases. In
      this review, written in honour of Juerg Tschopp who contributed so much to
      research on cell death and immunology, we discuss the functions of Bid and XIAP
      in the control of Fas DR-induced apoptosis signalling, and we speculate on how
      this knowledge could be exploited to develop novel regimes for treatment of
      cancer.

PMID- 21959934
TI  - Loss of programmed cell death 4 induces apoptosis by promoting the translation of
      procaspase-3 mRNA.
AB  - The programmed cell death 4 (Pdcd4), a translation inhibitor, plays an essential
      role in tumor suppression, but its role in apoptosis remains unclear. Here we
      show that Pdcd4 is a critical suppressor of apoptosis by inhibiting the
      translation of procaspase-3 mRNA. Pdcd4 protein decreased more rapidly through
      microRNA-mediated translational repression following apoptotic stimuli than did
      the activation of procaspase-3, cleavage of poly(ADP)ribose polymerase (PARP) by
      active caspase-3, and nuclear fragmentation. Strikingly, the loss of Pdcd4 by the
      specific RNA interference increased procaspase-3 expression, leading to its
      activation and PARP cleavage even without apoptotic stimuli, and sensitized the
      cells to apoptosis. Thus, our findings provide insight into a novel mechanism for
      Pdcd4 as a regulator of apoptosis.

PMID- 21959935
TI  - Silencing or knocking out the Na(+)/Ca(2+) exchanger-3 (NCX3) impairs
      oligodendrocyte differentiation.
AB  - Changes in intracellular [Ca(2+)](i) levels have been shown to influence
      developmental processes that accompany the transition of human oligodendrocyte
      precursor cells (OPCs) into mature myelinating oligodendrocytes and are required
      for the initiation of the myelination and re-myelination processes. In the
      present study, we explored whether calcium signals mediated by the selective
      sodium calcium exchanger (NCX) family members NCX1, NCX2, and NCX3, play a role
      in oligodendrocyte maturation. Functional studies, as well as mRNA and protein
      expression analyses, revealed that NCX1 and NCX3, but not NCX2, were divergently
      modulated during OPC differentiation into oligodendrocyte phenotype. In fact,
      whereas NCX1 was downregulated, NCX3 was strongly upregulated during
      oligodendrocyte development. The importance of calcium signaling mediated by NCX3
      during oligodendrocyte maturation was supported by several findings. Indeed,
      whereas knocking down the NCX3 isoform in OPCs prevented the upregulation of the
      myelin protein markers 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase) and
      myelin basic protein (MBP), its overexpression induced an upregulation of CNPase
      and MBP. Furthermore, NCX3-knockout mice showed not only a reduced size of spinal
      cord but also marked hypo-myelination, as revealed by decrease in MBP expression
      and by an accompanying increase in OPC number. Collectively, our findings
      indicate that calcium signaling mediated by NCX3 has a crucial role in
      oligodendrocyte maturation and myelin formation.

PMID- 21959936
TI  - [Diabetes and pregnancy].
AB  - Metabolic characteristics of physiological and diabetic pregnancies are
      discussed. The basic factor of these changes is the increasing insulin resistance
      throughout pregnancy, which in case of diabetes may result in hyperglycemia with
      undesirable clinical consequences and complications for both the mother and the
      fetus. Prevention of these complications by maintaining physiological metabolic
      state of diabetic pregnant women is possible, which is similar to that of healthy
      women. The aim of treatment of pregnant diabetics is to achieve normoglycemic
      state during the whole gestation that is possible by early diagnosis in case of
      gestational diabetes and by adequate preconception care in case of pregestational
      diabetes. To obtain desirable glycemic conditions insulin treatment is necessary
      in most of the cases together with adequate, quantitative nutrition therapy,
      while oral antidiabetic drugs during pregnancy and lactation are to be avoided.
      For adequate care of the cases with diabetes and pregnancy interdisciplinary
      diabetes centers with well-trained experts are required.

PMID- 21959937
TI  - [Description of the long-term effects of breast feeding in the Hungarian
      guidelines for infant nutrition].
AB  - AIMS: To identify and describe infant feeding policy documents in Hungary and
      compare them to the documents of other four European countries (England, Finland,
      Germany and Spain). The question was also addressed how the phenomenon of
      nutritional programming was represented in the documents. SUBJECTS: Policy
      documents on infant feeding were identified and analyzed in the five European
      countries by using uniform methods for searching and coding. RESULTS: Twenty-six
      documents were identified: 4 in England, 2 in Finland, 9 in Germany, 6 in Hungary
      and 5 in Spain. Altogether 203 statements linked to references were identified:
      benefits of breast-feeding in general (24%), protection against infections (32%),
      long-term advantages like the prevention of diabetes (31%) or allergy (12%).
      Considerable variations were found within and between countries in the evaluation
      of the duration and character of the positive effects. The majority of the
      statements in the Hungarian documents referred either to the role of breast
      feeding in infection protection (n = 8), or to long-term protective effects (n =
      13). CONCLUSION: Policy documents in the study countries varied both in their
      extent and in the description of the long-term effects of infant nutrition.
      Majority of the documents failed to contain evidence based discussion of the
      phenomenon of early nutritional programming.

PMID- 21959938
TI  - [Data about the sexual activity of Hungarian men].
AB  - In the last decades there was a considerable development in the field of sexual
      medicine, which is a relatively new discipline integrating studies on the
      physiology, biology, psycho-social and cultural aspects of sexuality of both
      genders including morbidities affecting sexual health and well being. Issues
      regarding sexuality are often neglected during routine medical consultations.
      There is lack of comparable data about the average sexual activity of men; many
      of them collected from commercial sources. AIM: This study aimed to collect
      reliable data about the sexual activity of Hungarian men. METHOD: Patients
      attending the andrology and urology outpatient department were asked during
      consultation about their intercourse frequency. RESULTS: Data of 723 men (age
      between 21-61 years) were evaluated. Mean of weekly intercourses was 3.1, with
      small difference between age decades. Only men over 50 years reported
      significantly less frequency (1.9/week). Other possible influencing factors were
      not analyzed. CONCLUSION: Comparing with available international data, Hungarian
      men seem to be among the most active male population worldwide.

PMID- 21959939
TI  - [Pharmacogenetics of insulin secretagogue antidiabetics].
AB  - Type 2 diabetes is making up to 90% of the all diabetic cases. In addition to
      insulin resistance, insufficient B-cell function also plays an important role in
      the pathogenesis of the disease. The insufficient production and secretion of
      insulin can be increased by secretagogue drugs, like sulfonylureas and incretin
      mimetics/enhancers. In recent years growing number of genetic failures of the B
      cells has been detected. These genetic variants can influence the efficacy of
      secretagogue drugs. Some of these gene polymorphisms were identified in the genes
      encoding the KATP channel (KCNJ11 and ABCC8). These mutations are able either to
      reduce or increase the insulin secretion and can modify the insulin response to
      sulfonylurea treatment. Other polymorphisms were found on genes encoding enzymes
      or transcription factors. In recent years, the genetic variants of TCF7L2 and its
      clinical importance have been intensely studied. Authors give a summary of the
      above gene polymorphisms and their role in insulin secretion.

PMID- 21959940
TI  - [Management of the common European viper's bite--a case report].
AB  - The common European viper is widespread throughout Europe. In Hungary it can be
      found mainly in the Zemplen Mountains, on the upper course of the Tisza River,
      and Zala and Somogy counties. Viper's bite is one of the rarest injuries that
      requires emergency medical care. The venom contains polypeptides and hydrolytic
      enzymes which have neurotoxic, cytotoxic, hemolytic and hemorrhagic effects.
      Local symptoms may include double points, pain, swelling, and suffusion at the
      site of the bite. Very occasionally, particularly in case of small children and
      elderly people, viper bite can cause life threatening angioedema, as well as
      shock and, therefore, professional medical help should always be sought
      preferably in a hospital that has a toxicology and poison control centre. Authors
      present the history of a 64-year-old nature enthusiast, who, after having been
      bitten by a viper, lost consciousness and experienced persistent local redness
      and pain. Soon after the viper bite, the patient suffered another potentially
      fatal accident, a stroke of lightning that he also survived. In connection with
      the case, authors provide an overview of the clinical symptoms caused by viper
      venom, and current issues of professional care.

PMID- 21959942
TI  - Physical activity status and postprandial lipaemia in older adults.
AB  - Physical activity-induced lowering of postprandial lipaemia is short-lived.
      However, little is known regarding the role of physical activity status on
      postprandial lipaemia. The purpose of the present study was to compare
      postprandial triacylglycerol concentrations in active and inactive older adults.
      A total of 26 older adults (aged 69.8+/-0.9 years, mean+/-SEM; 10 male and 16
      female) were analysed in a cross-sectional design. Based on accelerometer data,
      participants were divided into either the active group (>=150 min/week of
      moderate-intensity physical activity, N=15) or the inactive group (<150 min/week
      of moderate-intensity physical activity, N=11). After a 48-h period of physical
      activity avoidance and a 10-h overnight fast, participants consumed a test meal
      of moderate fat content (35%). Capillary blood samples were collected in the
      fasted state and at 2, 4, and 6 h postprandially. After adjusting for fasting
      triacylglycerol concentrations, body mass, body mass index and waist
      circumference, postprandial capillary triacylglycerol concentrations were
      significantly lower in the active than inactive group ( P=0.046). These findings
      demonstrate that regular physical activity lowers postprandial lipaemia
      independent of the acute effects of physical activity in older adults.

PMID- 21959943
TI  - Spinous process morphology: the effect of ageing through adulthood on spinous
      process size and relationship to sagittal alignment.
AB  - STUDY DESIGN: Blinded radiographic analysis of CT scans reformatted for precise
      lumbar spinous process (LSP) measurement. OBJECTIVE: To investigate the effect of
      ageing on LSP morphology and influence of LSP morphology on lumbar spine sagittal
      alignment. SUMMARY OF BACKGROUND DATA: There is little data reporting the
      influence of ageing on spinous process size. There is data describing the
      increase in size of other body parts with age, such as the femur, ears, vertebral
      body, and nose. Several old cadaveric and radiographic studies have reported the
      formation of osseous spurs within the supraspinous and interspinous ligaments.
      METHOD: 200 abdominal CT scans taken for trauma and vascular investigation were
      reformatted to allow precise bony measurement of the lumbar spine. Two observers
      were blinded from the age and demographics of the patients. Sagittal and coronal
      plane projections were used to measure the height and width of the spinous
      processes (L1-L5), respectively. The relationship between spinous process size,
      age, and supine lordosis was investigated. RESULTS: LSP height increases by 0.03
      0.07 mm/year (p < 10(-3) to 10(-8)) and width by 0.05-0.06 mm/year (p < 10(-11)
      to 10(-15)). Lumbar lordosis decreases with increasing LSP height (p < 0.0004)
      but is not related to increasing LSP width (p = 0.195). Supine lordosis increases
      by 0.1 degrees /year (p = 0.004). CONCLUSIONS: This study demonstrates that the
      dimensions of the LSP change with age. Increases in LSP height and even more
      impressive increases in LSP width occur with advancing age. There is an inverse
      relationship between lumbar lordosis and LSP height.

PMID- 21959945
TI  - Strain dependent selection of spin-slip phases in sputter deposited thin-film
      epitaxial holmium.
AB  - We report the structural and magnetic characterization of sputter deposited
      epitaxial Ho. We present room temperature characterization by atomic force
      microscopy and x-ray diffraction and temperature dependent characterization by x
      ray diffraction and neutron diffraction. The data show the onset and change of
      the magnetic state as a function of temperature. Films of different thickness,
      exhibiting signs of differing epitaxially induced strain, tend towards specific
      spin-slip phases in the low temperature regime. The more highly strained thinnest
      films tend towards values with a longer magnetic wavelength.

PMID- 21959946
TI  - Facile synthesis and altered ionization efficiency of diverse Nepsilon
      alkyllysine-containing peptides.
AB  - Protein lysine methylation is a biologically-important posttranslational
      modification. Given the increased use of alkyllysine-containing peptides to study
      protein methylation, we describe an efficient solid-phase synthesis to access
      various alkyllysine-containing peptides. As an exemplary application, we
      evaluated how ionization efficiency of the alkyllysine peptides affects mass
      spectrometric analysis.

PMID- 21959947
TI  - Immune response as a possible mechanism of long-lasting disease control in
      spontaneous remission of MLL/AF9-positive acute myeloid leukemia.
AB  - Spontaneous complete remission (CR) is a rare, poorly understood phenomenon in
      acute myeloid leukemia (AML). We describe the 10-year follow-up of a patient with
      MLL-AF9-positive AML (Muller et al. Eur J Haematol 73:62-66, 2004), including ex
      vivo antileukemic immune responses which may contribute to the long-lasting
      spontaneous CR (tantamount to cure). We could demonstrate strong in vitro
      cytotoxic activity mediated by the patient's serum (cryopreserved at diagnosis
      2001) against myeloid cell lines. We also addressed cellular cytotoxic activity
      against myeloid leukemia cells. When the patient's natural killer (NK) cells
      (obtained in 2007) were tested against the K562 cell line, upregulation of CD107
      occurred, implying that long-term CR in this patient could be due to NK cell
      mediated disease control.

PMID- 21959948
TI  - Abstracts of the Irish Endocrine Society 35th Annual Meeting. November 11-12,
      2011. Templepatrick, County Antrim, Northern Ireland.

PMID- 21959949
TI  - Anaesthetic outcomes in obese parturients: the effect of assessment in the high
      risk clinic.
AB  - BACKGROUND: Obese parturients are at high risk of complications during
      anaesthesia and early use of epidural analgesia in labour has been recommended
      for obese patients during labour. AIM: To assess the outcome of anaesthesia
      outpatient consultation for obese parturients. METHODS: We retrospectively
      compared outcomes of obese patients antenatally and an obese and non-obese
      control group over a 1-year period. Outcomes included potential airway problems,
      anaesthetic for caesarean section, use and success of epidural analgesia and
      cervical dilation at epidural placement. RESULTS: The proportion of obese
      patients who had predictable intubation difficulty was low (5%). Epidural use
      analgesia in labour (69 vs 36 vs 66%, P = 0.148) was similar between groups
      (obese, obese controls and non-obese controls, respectively). Cervical dilation
      at the time of epidural insertion in the obese group (2.0, 1.0-3.0 cm) was not
      different from obese controls (3.0, 1.75-5.75 cm). There was no difference in the
      number of attempts required to site the epidural between groups or the number of
      patients that required resiting of the epidural catheter. General anaesthesia was
      not required in any emergency case in this group. CONCLUSION: The outcomes of
      obese patients attending the anaesthetic clinic were mixed. Not all patients who
      were to advised have epidurals did so but those who did requested them in early
      labour and there was no requirement for general anaesthesia during emergency
      caesarean section and adverse airway events were avoided in this group.

PMID- 21959950
TI  - Therapeutic isolated limb perfusion (ILP) in the management of patients with
      advanced or recurrent limb melanoma.

PMID- 21959952
TI  - WT1 in disease: shifting the epithelial-mesenchymal balance.
AB  - WT1 is a versatile gene that controls transitions between the mesenchymal and
      epithelial state of cells in a tissue-context dependent manner. As such, WT1 is
      indispensable for normal development of many organs and tissues. Uncontrolled
      epithelial to mesenchymal transition (EMT) is a hallmark of a diverse array of
      pathologies and disturbance of mesenchymal to epithelial transition (MET) has
      been associated with a number of developmental abnormalities. It is therefore not
      surprising that WT1 has been linked to many of these. Here we review the role of
      WT1 in proper control of the mesenchymal-epithelial balance of cells and discuss
      how far these roles can explain the role of WT1 in a variety of disease states.

PMID- 21959951
TI  - Reducing preoperative fasting in elective adult surgical patients: a case-control
      study.
AB  - BACKGROUND: The practice of fasting from midnight prior to surgery is an outdated
      one. AIMS: The aim of this study was to assess the impact of an evidence-based
      protocol for reduced preoperative fasting on fasting times, patient safety, and
      comfort. METHODS: A non-randomised case-control study of preoperative fasting
      times among adult surgical patients undergoing elective procedures was conducted.
      Consecutive patients were allocated to a reduced preoperative fasting protocol
      allowing fluids and solids up to 2 and 6 h prior to anaesthesia, respectively (n
      = 21). These were compared to control patients identified from an historic study
      of preoperative fasting times who followed the traditional fast from midnight (n
      = 29). Fasting times and details of patients' subjective comfort were collected
      using an interview-assisted questionnaire. Incidence of intraoperative
      aspirations was obtained from anaesthetic records. RESULTS: Significant
      reductions in fasting times for fluids (p = 0.000) and solids (p = 0.000) were
      achieved following implementation of the fasting protocol. Less preoperative
      thirst (0.000), headache (0.012) and nausea (0.015) were reported by those who
      had a shorter fast. Intraoperative aspiration did not occur in either group.
      CONCLUSION: Implementation of this protocol for reduced preoperative fasting
      achieved an appreciable reduction in fasting times and enhanced patient comfort.
      Patient safety was not compromised. Further modifications of our protocols are
      necessary to meet the international best practice. We recommend its
      implementation across all surgical groups in our institution.

PMID- 21959953
TI  - New encoding schemes with infofuses.

PMID- 21959954
TI  - Overexpression of MUC1 enhances proangiogenic activity of non-small-cell lung
      cancer cells through activation of Akt and extracellular signal-regulated kinase
      pathways.
AB  - BACKGROUND: Angiogenesis is an important process required for tumor progression.
      Mucin 1 (MUC1) is a transmembrane glycoprotein that is aberrantly upregulated in
      many types of cancer, including non-small-cell lung cancer (NSCLC). However, the
      biological significance of MUC1 overexpression in lung cancer angiogenesis is not
      completely understood. METHODS: We showed that enforced expression of MUC1 in two
      NSCLC cell lines, A549 and NCI-H460, which have a low level of endogenous MUC1,
      promoted their ability to induce vascular endothelial growth factor (VEGF)
      dependent endothelial cell migration and tube formation. RESULTS: There was a
      significant increase in VEGF expression in MUC1-overexpressing NSCLC cells.
      Moreover, MUC1 overexpression resulted in a marked elevation in phosphorylated
      Akt and extracellular signal-regulated kinase (ERK)1/2, indicative of activation
      of both signaling pathways. Most importantly, inhibition of Akt or ERK signaling
      using specific chemical inhibitors restrained the proangiogenic activity of MUC1
      overexpressing NSCLC cells. CONCLUSIONS: Taken together, our present data
      demonstrate that the aberrant upregulation of MUC1 favors tumor angiogenesis in
      NSCLC, likely through the activation of both Akt and ERK pathways and elevation
      of VEGF production. MUC1 may thus be a potential antiangiogenic target in NSCLC.

PMID- 21959955
TI  - A "turn-on" fluorescent probe for hypochlorous acid: convenient synthesis, good
      sensing performance, and a new design strategy by the removal of C=N
      isomerization.
AB  - A new design strategy for the development of fluorescent turn-on chemodosimeters
      toward OCl(-) was proposed by the removal, but not the general inhibition, of the
      C=N isomerization. Accordingly, Flu-1 was prepared, which, as shown in the
      fluorescent picture, exhibited the off-on response for OCl(-), sensitively and
      selectively.

PMID- 21959956
TI  - The effect of conceptual and contextual familiarity on transfer performance.
AB  - Applying a previously learned concept to a novel problem is an important but
      difficult process called transfer. It is suggested that a commonsense analogy
      aids in transfer by linking novel concepts to familiar ones. How the context of
      practice affects transfer when learning using analogies is still unclear. This
      study investigated the effect of a commonsense analogy and context familiarity
      for transfer of physiological concepts. First year psychology students (n = 24)
      learned three concepts: Starling's law, Laplace's law, and laminar-turbulent
      flow. The control group saw standard explanations while the intervention group
      saw an additional commonsense analogy. The context of learning was the organ
      system used for two practice clinical cases which differed for all concepts.
      Testing consisted of 12 new clinical cases. Starling's law cases used the organ
      system from practice while the other concepts presented in both novel and
      familiar organ systems. Half of the sample repeated testing after 1 week delay.
      The outcome was ratings of explanations of cases on a 0-3 scale. The effect of
      analogy was significant (Mean = 1.24 with, 0.86 without, F(1,22) = 4.26, p <
      0.05) but not after delay (means of 1.08 and 0.75 respectively, F = (1,10), p =
      0.06) There was significant effect for familiar context (Same = 1.23 (Starling),
      different = 0.68 (Laplace) and 0.73 (laminar-turbulent flow) (F(2,44) = 5.14, p <
      0.01). Laplace's law and laminar turbulent flow cases in the familiar organ
      system had means of 1.65 and 1.77 respectively compared to novel cases with means
      of 0.74 and 0.68 (F(1,22) = 35.64, p < 0.0001). Similar effects were observed
      after delay. There was significant decay in performance after delay for all
      participants (immediate = 1.17, delayed = 0.91, F = 11.9 (1,10) p < 0.01). Common
      analogies aid conceptual understanding necessary for transfer. Despite conceptual
      aids, solving transfer problems is difficult.

PMID- 21959957
TI  - Prevalence of diabetes and prediabetes (impaired fasting glucose and/or impaired
      glucose tolerance) in urban and rural India: phase I results of the Indian
      Council of Medical Research-INdia DIABetes (ICMR-INDIAB) study.
AB  - AIMS/HYPOTHESIS: This study reports the results of the first phase of a national
      study to determine the prevalence of diabetes and prediabetes (impaired fasting
      glucose and/or impaired glucose tolerance) in India. METHODS: A total of 363
      primary sampling units (188 urban, 175 rural), in three states (Tamilnadu,
      Maharashtra and Jharkhand) and one union territory (Chandigarh) of India were
      sampled using a stratified multistage sampling design to survey individuals aged
      >= 20 years. The prevalence rates of diabetes and prediabetes were assessed by
      measurement of fasting and 2 h post glucose load capillary blood glucose.
      RESULTS: Of the 16,607 individuals selected for the study, 14,277 (86%)
      participated, of whom 13,055 gave blood samples. The weighted prevalence of
      diabetes (both known and newly diagnosed) was 10.4% in Tamilnadu, 8.4% in
      Maharashtra, 5.3% in Jharkhand, and 13.6% in Chandigarh. The prevalences of
      prediabetes (impaired fasting glucose and/or impaired glucose tolerance) were
      8.3%, 12.8%, 8.1% and 14.6% respectively. Multiple logistic regression analysis
      showed that age, male sex, family history of diabetes, urban residence, abdominal
      obesity, generalised obesity, hypertension and income status were significantly
      associated with diabetes. Significant risk factors for prediabetes were age,
      family history of diabetes, abdominal obesity, hypertension and income status.
      CONCLUSIONS/INTERPRETATIONS: We estimate that, in 2011, Maharashtra will have 6
      million individuals with diabetes and 9.2 million with prediabetes, Tamilnadu
      will have 4.8 million with diabetes and 3.9 million with prediabetes, Jharkhand
      will have 0.96 million with diabetes and 1.5 million with prediabetes, and
      Chandigarh will have 0.12 million with diabetes and 0.13 million with
      prediabetes. Projections for the whole of India would be 62.4 million people with
      diabetes and 77.2 million people with prediabetes.

PMID- 21959958
TI  - Do men develop type 2 diabetes at lower body mass indices than women?
AB  - AIMS/HYPOTHESIS: To describe the associations between age, sex and BMI at
      diagnosis of type 2 diabetes, and test the hypothesis that men are diagnosed with
      diabetes at lower average BMI than women of similar age. METHODS: Linear
      regression was used to estimate and compare the relationship between age and BMI
      at diagnosis among 51,920 men and 43,137 women included in a population-based
      diabetes register in Scotland for whom an index BMI measurement was taken within
      1 year of diabetes diagnosis. We also examined HbA(1c) values by sex within the
      same timescale. RESULTS: Mean BMI closest to date of diagnosis of type 2 diabetes
      mellitus was 31.83 kg/m(2) (SD 5.13) in men and 33.69 kg/m(2) (SD 6.43) in women.
      The inverse relationship between age and BMI at diagnosis of type 2 diabetes
      mellitus was significantly steeper in women than in men (slope estimate in men 
      0.12 kg/m(2) per year [95% CI -0.13, -0.12] women -0.18 kg/m(2) per year [95% CI 
      0.18, -0.17], p < 0.0001 for formal test of interaction). Mean BMI difference was
      most marked at younger ages and narrowed with advancing age. However, HbA(1c)
      levels within 1 year of diagnoses were broadly similar in men and women.
      CONCLUSIONS/INTERPRETATION: Men are diagnosed with type 2 diabetes at lower BMI
      than women across the age range. This observation may help explain why type 2
      diabetes is more common among middle-aged men in populations of European
      extraction. Whether the same pattern is also observed in other ethnic groups
      requires confirmation.

PMID- 21959959
TI  - Proinsulin-to-C-peptide ratio versus proinsulin-to-insulin ratio in the
      prediction of incident diabetes: the Insulin Resistance Atherosclerosis Study
      (IRAS).
AB  - AIMS: Associations of proinsulin-to-insulin ratios with incident type 2 diabetes
      have been inconsistent. The use of C-peptide as the denominator in the ratio may
      allow for better prediction because C-peptide concentration is not affected by
      hepatic insulin clearance. The objective of this paper was to compare fasting
      intact and split proinsulin-to-insulin ratios (PI/I, SPI/I) with intact and split
      proinsulin-to-C-peptide ratios (PI/C-pep, SPI/C-pep) in the prediction of type 2
      diabetes. METHODS: Prospective data on 818 multi-ethnic adults without diabetes
      at baseline from the Insulin Resistance Atherosclerosis Study (IRAS) were used.
      Insulin sensitivity (S(I)) and acute insulin response (AIR) were determined from
      frequently sampled intravenous glucose tolerance tests, and fasting intact and
      split proinsulin were measured using specific two-site monoclonal antibody-based
      immunoradiometric assays. Associations of proinsulin ratios with type 2 diabetes
      were determined using logistic regression and differences in prediction were
      assessed by comparing areas under the receiver operating characteristic curve
      (AROCs). RESULTS: In logistic regression analyses, PI/C-pep and SPI/C-pep were
      more strongly associated with incident type 2 diabetes (n = 128) than PI/I and
      SPI/I, and were significantly better predictors of diabetes in AROC analyses
      (PI/C-pep = 0.662 vs PI/I = 0.603, p = 0.02; SPI/C-pep = 0.690 vs SPI/I = 0.631,
      p = 0.01). Both PI/C-pep and SPI/C-pep were associated with type 2 diabetes after
      adjustment for age, sex, ethnicity, waist circumference, impaired glucose
      tolerance, lipids and S(I). Both PI/C-pep and SPI/C-pep were significantly
      associated with incident type 2 diabetes in models that included AIR.
      CONCLUSIONS: Proinsulin-to-C-peptide ratios were stronger predictors of diabetes
      in comparison with proinsulin-to-insulin ratios. These findings support the use
      of C-peptide as the denominator for proinsulin ratios, to more accurately reflect
      the degree of disproportional hyperproinsulinaemia.

PMID- 21959960
TI  - 1-Million droplet array with wide-field fluorescence imaging for digital PCR.
AB  - Digital droplet reactors are useful as chemical and biological containers to
      discretize reagents into picolitre or nanolitre volumes for analysis of single
      cells, organisms, or molecules. However, most DNA based assays require processing
      of samples on the order of tens of microlitres and contain as few as one to as
      many as millions of fragments to be detected. Presented in this work is a droplet
      microfluidic platform and fluorescence imaging setup designed to better meet the
      needs of the high-throughput and high-dynamic-range by integrating multiple high
      throughput droplet processing schemes on the chip. The design is capable of
      generating over 1-million, monodisperse, 50 picolitre droplets in 2-7 minutes
      that then self-assemble into high density 3-dimensional sphere packing
      configurations in a large viewing chamber for visualization and analysis. This
      device then undergoes on-chip polymerase chain reaction (PCR) amplification and
      fluorescence detection to digitally quantify the sample's nucleic acid contents.
      Wide-field fluorescence images are captured using a low cost 21-megapixel digital
      camera and macro-lens with an 8-12 cm(2) field-of-view at 1* to 0.85*
      magnification, respectively. We demonstrate both end-point and real-time imaging
      ability to perform on-chip quantitative digital PCR analysis of the entire
      droplet array. Compared to previous work, this highly integrated design yields a
      100-fold increase in the number of on-chip digitized reactors with simultaneous
      fluorescence imaging for digital PCR based assays.

PMID- 21959961
TI  - Surgery for cleft palate and velopharyngeal dysfunction.
AB  - Cleft palate is a common congenital anomaly that, if left untreated, results in
      subsequent velopharyngeal dysfunction. After surgical repair of the palatal
      cleft, patients must be monitored clinically for any postoperative velopharyngeal
      dysfunction. If this sequela develops, patients must be evaluated in a
      multidisciplinary manner with diagnostic procedures performed and individualized
      care plans made prior to embarking upon surgery for velopharyngeal dysfunction.
      This article discusses surgical management of patients with cleft palate as well
      as the proper workup and management of postoperative velopharyngeal dysfunction.

PMID- 21959963
TI  - Flash visual evoked potentials are unreliable as markers of ICP due to high
      variability in normal subjects.
AB  - BACKGROUND: Previous publications have suggested a high correlation between flash
      visual evoked potential (F-VEP) N2 peak latency and intracranial pressure. This
      would enable F-VEP to be used as a non-invasive and inexpensive method to
      estimate ICP in a number of settings. However, basic knowledge about variability
      across subjects and test-retest properties of the F-VEP is lacking. METHODS:
      Fifteen healthy adult subjects were tested on three different occasions. F-VEP
      responses were recorded using international standards. FINDINGS: For the tested
      population, mean N2 latency was 65.7 ms (SD 10.7 ms) and the range was 48-110 ms.
      Intra-individual variability was high, in four of the 15 subjects more than 15 ms
      between testing sessions. The same was found for P2 latency and for N2 and P2
      amplitudes. The response waveform was very variable and unambiguous marking of
      peaks was often difficult. One out of the 15 subjects had a very poorly developed
      F-VEP response, but a normal pattern-reversal VEP response. CONCLUSIONS: F-VEP
      has a wide range of latency, amplitude and waveform across normal subjects. A
      large proportion of subjects also had a high intra-individual variability over
      time. This variability makes F-VEPs unreliable as a marker for intracranial
      pressure, and caution in interpreting F-VEP changes in clinical work is advised.

PMID- 21959964
TI  - Flash visual evoked potentials are unreliable as markers of ICP due to high
      variability in normal subjects.

PMID- 21959965
TI  - Skull base reconstruction using various types of galeal flaps.
AB  - BACKGROUND: Failure of skull base reconstruction is a life-threatening issue.
      This study describes surgical techniques utilising various types of galeal flaps
      and reports on outcome of these procedures for skull base reconstruction. METHOD:
      Clinical records of 136 patients (75 men, 61 women; mean age, 50.0 years) who
      required skull base reconstruction with galeal flaps were reviewed
      retrospectively. Patients had undergone skull base surgeries with simultaneous
      reconstruction for benign tumours in 77 patients, malignant tumours in 53, and
      other lesions in 6. We repaired dural defects using a fascial patch, and covered
      the skull base defects using various types of galeal flap according to the size
      and location of the skull base defects. Routine spinal drainage was not used in
      any patients. FINDINGS: Reconstruction was performed as planned in all patients.
      We utilised a galea frontalis flap in 17 patients, temporoparietal galeal flap in
      95, temporoparietal galeal flap with calvarial bone in 9, and bipedicled
      temporoparietal galeal flap in 15. Postoperative complications included scalp
      wound necrosis in 8 patients (5.9%), transient leakage of cerebrospinal fluid in
      3 (2.2%), and intracranial infection in 2 (1.5%). Necrosis of the galeal flaps
      was not encountered. CONCLUSIONS: Galea is a well-vascularised tissue with
      homogenous thickness. Since the galeal layer covers the entire head area, various
      types of galeal flap can be elevated to cover any size and location of skull base
      defect.

PMID- 21959966
TI  - Rosai-Dorfman disease presenting as a thoracic intradural extramedullary spinal
      tumor but without extraspinal manifestations.

PMID- 21959967
TI  - Tumor-targeted gene therapy using Adv-AFP-HRPC/IAA prodrug system suppresses
      growth of hepatoma xenografted in mice.
AB  - Clinical efficacy of current therapies for hepatocellular carcinoma (HCC)
      treatment is limited. Indole-3-acetic acid (IAA) is non-toxic for mammalian
      cells. Oxidative decarboxylation of IAA by horseradish peroxidase (HRP) leads to
      toxic effects of IAA. The purpose of this study was to investigate the effects of
      a novel gene-targeted enzyme prodrug therapy with IAA on hepatoma growth in vitro
      and in vivo mouse hepatoma models. We generated a plasmid using adenovirus to
      express HRP isoenzyme C (HRPC) with the HCC marker, alpha-fetoprotein (AFP), as
      the promoter (pAdv-AFP-HRPC). Hepatocellular cells were infected with pAdv-AFP
      HRPC and treated with IAA. Cell death was detected using MTT assay. Hepatoma
      xenografts were developed in mice by injection of mouse hepatoma cells. The size
      and weight of tumors and organs were evaluated. Cell death in tumors was assessed
      using hematoxylin and eosin-stained tissue sections. HRPC expression in tissues
      was detected using Reverse Transcriptase-Polymerase Chain Reaction. IAA
      stimulated death of hepatocellular cells infected with pAdv-AFP-HRPC, in a dose-
      and time-dependent manner, but not in control cells. Growth of hepatoma
      xenografts, including the size and weight, was inhibited in mice treated with
      pAdv-AFP-HRPC and IAA, compared with that in control group. pAdv-AFP-HRPC/IAA
      treatment induced cell death in hepatoma xenografts in mice. HRPC gene expressed
      only in hepatoma, but not in other normal organs of mice. pAdv-AFP-HRPC/IAA
      treatment did not cause any side effects on normal organs. These findings suggest
      that pAdv-AFP-HRPC/IAA enzyme/prodrug system may serve as a strategy for HCC
      therapy.

PMID- 21959969
TI  - Synthesis, characterization and magnetic properties of four new organically
      templated metal sulfates [C5H14N2][M(II)(H2O)6](SO4)2, (M(II) = Mn, Fe, Co, Ni).
AB  - A series of novel organically templated metal sulfates,
      [C(5)H(14)N(2)][M(II)(H(2)O)(6)](SO(4))(2) with (M(II) = Mn (1), Fe (2), Co (3)
      and Ni (4)), have been successfully synthesized by slow evaporation and
      characterized by single-crystal X-ray diffraction as well as with infrared
      spectroscopy, thermogravimetric analysis and magnetic measurements. All compounds
      were prepared using a racemic source of the 2-methylpiperazine and they
      crystallized in the monoclinic systems, P2(1)/n for (1, 3) and P2(1)/c for (2,4).
      Crystal data are as follows: [C(5)H(14)N(2)][Mn(H(2)O)(6)](SO(4))(2), a =
      6.6385(10) A, b = 11.0448(2) A, c = 12.6418(2) A, beta = 101.903(10) degrees , V
      = 906.98(3) A(3), Z = 2; [C(5)H(14)N(2)][Fe(H(2)O)(6)](SO(4))(2), a = 10.9273(2)
      A, b = 7.8620(10) A, c = 11.7845(3) A, beta = 116.733(10) degrees , V = 904.20(3)
      A(3), Z = 2; [C(5)H(14)N(2)][Co(H(2)O)(6)](SO(4))(2), a = 6.5710(2) A, b =
      10.9078(3) A, c = 12.5518(3) A, beta = 101.547(2) degrees , V = 881.44(4) A(3), Z
      = 2; [C(5)H(14)N(2)][Ni(H(2)O)(6)](SO(4))(2), a = 10.8328(2) A, b = 7.8443(10) A,
      c = 11.6790(2) A, beta = 116.826(10) degrees , V = 885.63(2) A(3), Z = 2. The
      three-dimensional structure networks for these compounds consist of isolated
      [M(II)(H(2)O)(6)](2+) and [C(5)H(14)N(2)](2+) cations and (SO(4))(2-) anions
      linked by hydrogen-bonds only. The use of racemic 2-methylpiperazine results in
      crystallographic disorder of the amines and creation of inversion centers. The
      magnetic measurements indicate that the Mn complex (1) is paramagnetic, while
      compounds 2, 3 and 4, (M(II) = Fe, Co, Ni respectively) exhibit single ion
      anisotropy.

PMID- 21959968
TI  - Factors influencing the use of a Web-based application for supporting the self
      care of patients with type 2 diabetes: a longitudinal study.
AB  - BACKGROUND: The take-up of eHealth applications in general is still rather low
      and user attrition is often high. Only limited information is available about the
      use of eHealth technologies among specific patient groups. OBJECTIVE: The aim of
      this study was to explore the factors that influence the initial and long-term
      use of a Web-based application (DiabetesCoach) for supporting the self-care of
      patients with type 2 diabetes. METHODS: A mixed-methods research design was used
      for a process analysis of the actual usage of the Web application over a 2-year
      period and to identify user profiles. Research instruments included log files,
      interviews, usability tests, and a survey. RESULTS: The DiabetesCoach was
      predominantly used for interactive features like online monitoring, personal
      data, and patient-nurse email contact. It was the continuous, personal feedback
      that particularly appealed to the patients; they felt more closely monitored by
      their nurse and encouraged to play a more active role in self-managing their
      disease. Despite the positive outcomes, usage of the Web application was hindered
      by low enrollment and nonusage attrition. The main barrier to enrollment had to
      do with a lack of access to the Internet (146/226, 65%). Although 68% (34/50) of
      the enrollees were continuous users, of whom 32% (16/50) could be defined as
      hardcore users (highly active), the remaining 32% (16/50) did not continue using
      the Web application for the full duration of the study period. Barriers to long
      term use were primarily due to poor user-friendliness of the Web application (the
      absence of "push" factors or reminders) and selection of the "wrong" users; the
      well-regulated patients were not the ones who could benefit the most from system
      use because of a ceiling effect. Patients with a greater need for care seemed to
      be more engaged in long-term use; highly active users were significantly more
      often medication users than low/inactive users (P = .005) and had a longer
      diabetes duration (P = .03). CONCLUSION: Innovations in health care will diffuse
      more rapidly when technology is employed that is simple to use and has applicable
      components for interactivity. This would foresee the patients' need for
      continuous and personalized feedback, in particular for patients with a greater
      need for care. From this study several factors appear to influence increased use
      of eHealth technologies: (1) avoiding selective enrollment, (2) making use of
      participatory design methods, and (3) developing push factors for persistence.
      Further research should focus on the causal relationship between using the
      system's features and actual usage, as such a view would provide important
      evidence on how specific technology features can engage and captivate users.

PMID- 21959970
TI  - "These boots were made for walking": the isotopic analysis of a C(4) Roman
      inhumation from Gravesend, Kent, UK.
AB  - As part of the road widening scheme between London and Dover, Oxford Archaeology
      South uncovered a large boundary ditch of Iron Age origin that contained Iron Age
      and Roman inhumations, adjacent to which was a small mid-late Roman cemetery,
      interpreted as a rural cemetery for Romano-British farmers. Grave goods in the
      cemetery were restricted to a few individuals with hobnailed boots. Bulk bone
      collagen isotopic analysis of 11 skeletons of Iron Age and Roman date gave a
      typical C(3) terrestrial signal (average delta(13) C = -19.80/00, delta(15) N =
      9.30/00), but also revealed one (SK12671) with a diet which included a
      substantial C(4) component (delta(13) C = -15.20/00, delta(15) N = 11.20/00).
      This is only the second such diet reported in Roman Britain. Subsequent delta(18)
      O(c) and (87) Sr/(86) Sr measurements on the dental enamel in this individual
      were, however, consistent with a "local" origin, indicating that either C(4)
      protein was consumed in Late Roman Britain, or that he came from somewhere else,
      but where conditions gave rise to similar isotopic values. If we accept the
      latter, then it indicates that using oxygen and strontium isotopes alone to
      identify "incomers" may be problematic. The provision of hobnailed boots for the
      dead appears to have had a strong symbolic element in Late Roman Britain. We
      suggest that in this case the boots may be significant, in that he was being
      equipped for the long march home.

PMID- 21959971
TI  - Effects of combining field strengths on auditory functional MRI group analysis:
      1.5T and 3T.
AB  - PURPOSE: To evaluate effects of combining functional magnetic resonance imaging
      (fMRI) data acquired from different field strengths on group analysis as a
      function of the number of subjects at each field strength. MATERIALS AND METHODS:
      In all, 28 subjects (18 at 3T) participated in an auditory task of passively
      listening to a 0.75s segment of jazz music in an event-related design. Results of
      single-subject analysis were combined to create all possible subject combinations
      for a group size of eight subjects from each of the 3T and 1.5T pools, comprising
      subject mixtures of (3T/1.5T) 0/8, 2/6, 4/4, 6/2, and 8/0. Group analysis
      performance of each subject permutation was measured by receiver operating
      characteristic (ROC) curves and activation overlap maps. RESULTS: While area
      under ROC curves, extent of activation in the gold standard region, and
      reliability of activation increased with the number of 3T subjects, marginal gain
      decreased. ROC performance overlap across mixtures was observed, indicating that
      some combinations of subjects markedly outperformed others. For detection of
      activation, 4/4 was arguably the minimum mixture level that was comparable to 3T
      only group results. CONCLUSION: Inclusion of 1.5T data does not necessarily
      reduce the validity of group analysis. Lower field strength data was found only
      to limit detection power, but did not affect specificity. Within the limits of
      realignment error, these results should also extend to group longitudinal
      analyses of subject mixtures from different field strengths.

PMID- 21959972
TI  - Characterization of dihydroartemisinin-resistant colon carcinoma HCT116/R cell
      line.
AB  - Dihydroartemisinin (DHA) is an important artemisinin derivative and presents
      profound anti-tumor potential. A DHA-resistant cell line named HCT116/R derived
      from colon carcinoma cell line HCT116 was established in our previous study.
      Herein, we found that HCT116/R cells were much more resistant to DHA- or
      artesunate-induced proliferation inhibition and more tolerant to DHA-induced cell
      cycle arrest and apoptosis compared with those of the parent HCT116 cells. The
      protein levels of P-glycoprotein and MDR-associated protein 1 and the
      accumulation of doxorubicin in cells were similar in both cell lines. Moreover,
      HCT116/R cells were still sensitive to camptothecin- and doxorubicin-induced cell
      growth inhibition. To further explore the characterization of HCT116/R cell line,
      a proteomic study employing two-dimensional gel electrophoresis and matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry was
      performed. Eight different expressed proteins between the two cell lines were
      identified including some heat shock proteins, annexins, etc. This study not only
      indicates that exposure to DHA may not induce a tumor multi-drug-resistant
      phenotype but also affords new clues for the further investigation of the anti
      cancer mechanisms of DHA and other artemisinin derivatives.

PMID- 21959973
TI  - Human tissue kallikrein 1 gene delivery inhibits PDGF-BB-induced vascular smooth
      muscle cells proliferation and upregulates the expressions of p27Kip1 and
      p2lCip1.
AB  - Tissue kallikrein 1 cleaves kininogen substrate to produce vasoactive kinin
      peptides that have been implicated in inhibiting neointimal hyperplasia in rat
      carotid arteries after balloon injury. However, its effects on the proliferation,
      cell cycle and its mechanisms, for example, cyclin-dependent kinase inhibitors,
      p27(Kip1) and p2l(Cip1) in vascular biology are poorly understood. The objective
      of this study was to explore the effects of human tissue kallikrein 1 (hTK1)
      mediated by recombinant adenovirus (Ad-hTK1) on proliferation and cell cycle of
      vascular smooth muscle cells (VSMCs) derived from spontaneously hypertensive rats
      induced by platelet-derived growth factor-BB (PDGF-BB) in vitro. The results
      showed that, within a given multiplicity of infection (MOI) and time, the hTK1
      gene delivery inhibited PDGF-BB-stimulating VSMCs growth in a concentration
      dependent (20-100 MOI) and time-dependent (2-5 days) manner by cell counting,
      with a peak inhibition rate at 36.3% at 72 h (P < 0.01). In addition, hTK1 gene
      delivery significantly suppressed PDGF-BB-induced proliferation of VSMCs by
      methyl thiazolyl tetrazoliuin assay, and decreased the percentage of cells in the
      S phase and in DNA synthesis by flow cytometry, with a peak inhibition rate at
      30.2 and 36.4%, respectively (P < 0.01). Western blot assay showed that the
      protein levels of p27(Kip1) and p2l(Cip1) in cells infected with Ad-hTK1 were
      much more abundant than those in cells only induced by PDGF-BB, with up
      modulating rates at 51.8 and 58.7%, respectively (P < 0.001). We also observed
      that the effects of hTK1 gene delivery in inhibiting VSMCs proliferation,
      arresting cell cycling in G(0)/G(1) phase and up-regulating the expression of
      p27(Kip1) and p2l(Cip1) could be blocked by icatibant (Hoe 140), a specific
      bradykinin B(2) receptor antagonist. Taken together, these results demonstrated
      that hTK1 overexpressed by recombinant adenovirus potently inhibits VSMCs
      proliferation that is required for neointimal hyperplasia and restenosis, and may
      activate p27(Kip1) and p2l(Cip1) signaling pathways via bradykinin B(2) receptor.

PMID- 21959974
TI  - A low prevalence of MYH7/MYBPC3 mutations among familial hypertrophic
      cardiomyopathy patients in India.
AB  - Familial Hypertrophic Cardiomyopathy (FHC) is an autosomal dominant disorder
      affecting the cardiac muscle and exhibits varied clinical symptoms because of
      genetic heterogeneity. Several disease causing genes have been identified and
      most code for sarcomere proteins. In the current study, we have carried out
      clinical and molecular analysis of FHC patients from India. FHC was detected
      using echocardiography and by analysis of clinical symptoms and family history.
      Disease causing mutations in the beta-cardiac myosin heavy chain (MYH7) and
      Myosin binding protein C3 (MYBPC3) genes were identified using Polymerase Chain
      Reaction-Deoxyribose Nucleic Acid (PCR-DNA) sequencing. Of the 55 patient samples
      screened, mutations were detected in only nineteen in the two genes; MYBPC3
      mutations were identified in 12 patients while MYH7 mutations were identified in
      five, two patients exhibited double heterozygosity. All four MYH7 mutations were
      missense mutations, whereas only 3/9 MYPBC3 mutations were missense mutations.
      Four novel mutations in MYBPC3 viz. c.456delC, c.2128G>A (p.E710K), c.3641G>A
      (p.W1214X), and c.3656T>C (p.L1219P) and one in MYH7 viz. c.965C>T (p.S322F) were
      identified. A majority of missense mutations affected conserved amino acid
      residues and were predicted to alter the structure of the corresponding mutant
      proteins. The study has revealed a greater frequency of occurrence of MYBPC3
      mutations when compared to MYH7 mutations.

PMID- 21959975
TI  - Lipopolysaccharide upregulates the expression of corticotropin-releasing hormone
      via MAP kinase pathway in rat peritoneal macrophages.
AB  - The stress neuropeptide, corticotropin-releasing hormone (CRH) is expressed in
      peripheral tissues and inflammatory sites and is implicated in the modulation of
      the inflammatory response in a paracrine/ autocrine manner. However, the
      mechanisms by which CRH expression is regulated in peripheral immune cells are
      unclear. In this article, we address this question by employing primary rat
      peritoneal macrophages treated with lipopolysaccharide (LPS). Our results showed
      that CRH could be detected at the mRNA and protein levels in normal peritoneal
      macrophages and the levels increased significantly and reached a peak at 4 h
      after stimulation with 100 ng/ml LPS. Furthermore, LPS-induced CRH expression was
      inhibited by pretreatment with PD98059, a specific MAP kinase inhibitor, in a
      dose-dependent fashion in which the mRNA and protein levels of CRH was decreased
      by 90% and 95%, respectively. In addition, pretreatment with 50 MUM SB203580, a
      p38 MAPK inhibitor, led to the decrease of CRH mRNA level by about 41%.
      Altogether, these results demonstrate that LPS significantly upregulates CRH
      expression through MAP kinase signaling pathway in rat peritoneal macrophages.

PMID- 21959976
TI  - VPA inhibits breast cancer cell migration by specifically targeting HDAC2 and
      down-regulating Survivin.
AB  - Cell migration plays major roles in human breast cancer-related death, but the
      molecular mechanisms remain unclear. Valproic acid (VPA) is a broad-spectrum
      inhibitor of class I and II histone deacetylases and shows great anticancer
      activity in a variety of human cancers including breast cancer. In this study, we
      found that VPA significantly inhibited cell migration but not proliferation of
      human breast cancer MDA-MB-231 cells. Mechanistic studies found that VPA
      significantly inhibited the expression of Survivin. Knockdown of Survivin could
      obviously inhibited cell migration, while over-expression of Survivin markedly
      rescued the inhibition of VPA on cell migration. Further studies found that
      knockdown of HDAC2 completely mimicked the effects of VPA on Survivin and cell
      migration, and over-expression of Survivin could also rescue the effects of HDAC2
      knockdown on cell migration. Collectively, these results indicated that HDAC2 may
      be the specific target of VPA in breast cancer cells, and specific inhibition of
      HDAC2, especially by small molecular chemicals may lead to less side-effects and
      provide a better strategy than VPA application for human breast cancer treatment.

PMID- 21959977
TI  - 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) facilitates curcumin
      induced melanoma cell apoptosis by enhancing ceramide accumulation, JNK
      activation, and inhibiting PI3K/AKT activation.
AB  - The majority of metastatic melanomas are resistant to different chemotherapeutic
      agents, consequently, the search for novel anti-melanoma agents and adjuvant is
      urgent. Here, we found that 1-phenyl-2-decanoylamino-3-morpholino-1-propanol
      (PDMP), an inhibitor of glycosphingolipid biosynthesis, enhanced curcumin-induced
      cell growth inhibition and apoptosis in two melanoma cell lines (WM-115 and B16).
      PDMP facilitated curcumin-induced ceramide accumulation; the latter contributed
      to melanoma cell apoptosis. PDMP also dramatically enhanced curcumin-induced c
      Jun N-terminal kinase activation, which was important to melanoma cell apoptosis.
      Meanwhile, curcumin plus PDMP treatment largely inhibited the activation of pro
      survival PI3K/AKT signal pathway. In conclusion, PDMP-sensitized curcumin-induced
      melanoma cell growth inhibition and apoptosis in vitro due to changes of multiple
      signal events. Combining PDMP with curcumin may represent a new therapeutic
      intervention against melanoma.

PMID- 21959978
TI  - Crystal structure of sulfotransferase STF9 from Mycobacterium avium.
AB  - Sulfotransferases catalyze the sulfate conjugation of a wide variety of
      endogenous and exogenous molecules. Human pathogenic mycobacteria produce
      numerous sulfated molecules including sulfolipids which are well related to the
      virulence of several strains. The genome of Mycobacterium avium encodes eight
      putative sulfotransferases (stf1, stf4-stf10). Among them, STF9 shows higher
      similarity to human heparan sulfate 3-O-sulfotransferase isoforms than to the
      bacterial STs. Here, we determined the crystal structure of sulfotransferase STF9
      in complex with a sulfate ion and palmitic acid at a resolution of 2.6 A. STF9
      has a spherical structure utilizing the classical sulfotransferase fold. STF9
      exclusively possesses three N-terminal alpha-helices (alpha1, alpha2, alpha3)
      parallel to the 3'-phosphoadenosine-5'-phosphosulfate (PAPS) binding motif. The
      sulfate ion binds to the PAPS binding structural motif and the palmitic acid
      molecule binds in the deep cleft of the predicted substrate binding site
      suggesting the nature of endogenous acceptor substrate of STF9 resembles palmitic
      acid. The substrate binding site is covered by a flexible loop which may have
      involvement in endogenous substrate recognition. Based on the mutational study
      (Hossain et al., Mol Cell Biochem 350:155-162; 2011) and structural resemblance
      of STF9-sulfate ion-palmitic acid complex to the hHS3OST3 complex with PAP (3'
      phosphoadenosine-5'-phosphate) and an acceptor sugar chain, Glu170 and Arg96 are
      appeared to be catalytic residues in STF9 sulfuryl transfer mechanism.

PMID- 21959979
TI  - Phase II study of weekly docetaxel and fixed dose rate gemcitabine in patients
      with previously treated advanced soft tissue and bone sarcoma.
AB  - PURPOSE: The purpose of this prospective multicenter phase II study was to
      evaluate the efficacy and toxicity of weekly docetaxel and fixed dose rate
      gemcitabine in patients with previously treated advanced soft tissue and bone
      sarcoma. METHODS: Patients with advanced soft tissue or bone sarcoma, previously
      treated with ifosfamide and anthracycline-based chemotherapies, were treated with
      docetaxel (35 mg/m(2) over 60 min) and gemcitabine (1,000 mg/m(2) over 100 min)
      on days 1 and 8 of every 3-week cycle. RESULTS: From September 2008 to August
      2010, 30 patients were enrolled; 24 (80.0%) were men and median patient age was
      45 years (range 17-70 years). The patients received a total of 136 cycles of
      therapy (median 4 cycles per patient; range 1-15 cycles). Of these 30 patients,
      none achieved complete response (CR) and 5 achieved a partial response (PR),
      making the overall response rate 16.7% (95% CI, 2.5-30.8%). Twelve patients had
      stable disease (SD), resulting in tumor control (CR or PR or SD) in 17 of 30
      patients (56.7%). Median progression-free survival was 2.5 months (range 0.8-15.3
      months), and median overall survival was 8.4 months (range 1.4-22.3 months).
      Grade 3 or 4 neutropenia, thrombocytopenia, and anemia were observed in 17
      (56.7%), 13 (43.4%), and 4 (13.3%) patients, respectively. None of these
      patients, however, had febrile neutropenia or bleeding events, and all non
      hematologic toxicities were manageable. CONCLUSIONS: The combination of weekly
      docetaxel and fixed dose rate gemcitabine was tolerable and may be an active
      regimen in patients with previously treated advanced sarcoma.

PMID- 21959980
TI  - Cerium oxide nanoclusters: commensurate with concepts of polyoxometalate
      chemistry?
AB  - The mixed-valent cerium(III/IV) oxide clusters {Ce(10)} and {Ce(22)}, derived
      from condensation reactions of cerium carboxylate coordination polymers, exhibit
      molecular growth tendencies similar to those of 'classical' group V and VI
      polyoxometalates, but with increasing nuclearity approach the structure of the
      parental oxide, CeO(2).

PMID- 21959982
TI  - The local physical structure of amorphous hydrogenated boron carbide: insights
      from magic angle spinning solid-state NMR spectroscopy.
AB  - Magic angle spinning solid-state nuclear magnetic resonance spectroscopy
      techniques are applied to the elucidation of the local physical structure of an
      intermediate product in the plasma-enhanced chemical vapour deposition of thin
      film amorphous hydrogenated boron carbide (B(x)C:H(y)) from an orthocarborane
      precursor. Experimental chemical shifts are compared with theoretical shift
      predictions from ab initio calculations of model molecular compounds to assign
      atomic chemical environments, while Lee-Goldburg cross-polarization and
      heteronuclear recoupling experiments are used to confirm atomic connectivities. A
      model for the B(x)C:H(y) intermediate is proposed wherein the solid is dominated
      by predominantly hydrogenated carborane icosahedra that are lightly cross-linked
      via nonhydrogenated intraicosahedral B atoms, either directly through B-B bonds
      or through extraicosahedral hydrocarbon chains. While there is no clear evidence
      for extraicosahedral B aside from boron oxides, ~40% of the C is found to exist
      as extraicosahedral hydrocarbon species that are intimately bound within the
      icosahedral network rather than in segregated phases.

PMID- 21959981
TI  - MicroRNA cloning and sequencing in osteosarcoma cell lines: differential role of
      miR-93.
AB  - BACKGROUND: Studies show that abnormalities in non-coding genes can contribute to
      carcinogenesis; microRNA levels may modulate cancer growth and metastatic
      diffusion. METHOD: MicroRNA libraries were built and sequenced from two
      osteosarcoma cell lines (MG-63 and 143B), which differ in proliferation and
      transmigration. By cloning and transfection, miR-93, expressed in both cell
      lines, was then investigated for its involvement in osteosarcoma progression.
      RESULTS: Six of the 19 miRNA identified were expressed in both cell lines with
      higher expression levels of miR-93 in 143B and in primary osteosarcoma cultures
      compared to normal osteoblasts. Interestingly, levels of miR-93 were
      significantly higher in metastases from osteosarcoma than in paired primary
      tumours. When 143B and MG-63 were transfected with miR-93, clones appeared to
      respond differently to microRNA overexpression. Ectopic expression of miR-93 more
      significantly increased cell proliferation and invasivity in 143B than in MG-63
      clones. Furthermore, increased mRNA and protein levels of E2F1, one of the
      potential miR-93 targets, were seen in osteosarcoma cellular clones and its
      involvement in 143B cell proliferation was confirmed by E2F1 silencing.
      CONCLUSION: Although further studies are needed to evaluate miRNA involvement in
      osteosarcoma progression, miR-93 overexpression seems to play an important role
      in osteosarcoma cell growth and invasion.

PMID- 21959983
TI  - Dynamic changes of PIRH2 and p27kip1 expression in injured rat sciatic nerve.
AB  - p53-induced ring-H2 protein (PIRH2), a newly identified E3 ubiquitin ligase, has
      been reported to be interacted with p27Kip1 and promote ubiquitination of p27Kip1
      independently of p53. p27kip1, a member of the Cip/Kip family of cyclin-dependent
      kinases inhibitors (CKIs), was shown to control cell cycle progression and
      promote cell proliferation. While the distribution and function of PIRH2 and
      p27kip1 in nervous system lesion and regeneration remains unclear. Here, we
      performed a sciatic nerve injury model in adult rats and studied the dynamic
      changes of PIRH2 and p27kip1 expression by western blot and RT-PCR in injured rat
      sciatic nerve. Sciatic nerve crush resulted in a significant up-regulation of
      PIRH2 and a down-regulation of p27kip1. Besides, we observed that they were
      expressed widely in both Schwann cells and axons in adult rat sciatic nerve by
      double immunofluorescence staining. Results obtained by coimmunoprecipitation and
      double labeling further showed their interaction in the regenerating process.
      Thus, these results indicate that PIRH2 and p27kip1 likely play an important role
      in peripheral nerve injury and regeneration.

PMID- 21959984
TI  - Predictive factors for platelet count after laparoscopic splenectomy in cirrhotic
      patients.
AB  - PURPOSE: The purpose of our study was to investigate predictive factors for
      platelet count at 1 month after splenectomy in patients with liver cirrhosis.
      METHODS: A total of 60 patients with liver cirrhosis who were treated with
      splenectomy from January 2005 to December 2006 were enrolled in the study
      (hepatitis C, n = 50; hepatitis B, n = 6; alcoholism, n = 2; others, n = 2).
      Various preoperative clinical characteristics, including spleen weight, were
      analyzed by simple and multiple linear regressions to study the relationship
      between platelet count before and after splenectomy. RESULTS: Platelet count
      increased significantly after splenectomy. After simple linear regression, spleen
      weight, preoperative platelet count, lymphocyte count, and total bilirubin were
      significantly correlated with platelet count after splenectomy. Spleen weight,
      preoperative platelet count, and lymphocyte count also had a significant
      correlation after multiple linear regression analysis. CONCLUSIONS: Platelet
      count after splenectomy in cirrhotic patients can be predicted on the basis of
      preoperative clinical characteristics. When selecting patients for splenectomy,
      spleen weight, preoperative platelet count, and lymphocyte count should be taken
      into consideration.

PMID- 21959985
TI  - Is there an association between otitis media and nasal polyposis?
AB  - The association between otitis media with effusion (OME) and nasal polyposis (NP)
      is poorly described. However, two different approaches to this problem seem to
      come from the few studies concerning both otitis media and NP in the literature.
      One study was based on the assessment of a population of patients presenting with
      NP, with the authors interested in patients among the studied population who
      complained of ear-related symptoms and developed OME (rhinologic approach). Other
      studies were based on the assessment of a population of patients developing a
      particular OME, with the authors interested in characterizing this condition they
      named eosinophilic otitis media (otologic approach). The article reviews currents
      concepts in the relationship between OME and NP. It appears that regardless of
      the approach to the problem of interest (rhinologic or otologic approach), OME
      and NP seem to be closely related. Moreover, some striking similarities can be
      noted between the different entities described in the different studies reviewed,
      and all authors seem to agree that the middle ear has a central role in the
      concept of united airways inflammatory disease. Otologists and rhinologists
      should work together on a single approach that allows for better management of
      inflammatory disease leading to the formation of polyps, development of
      concurrent asthma, appearance of aspirin intolerance, and finally involvement of
      the middle ear.

PMID- 21959986
TI  - Using conjoint analysis to measure the acceptability of rectal microbicides among
      men who have sex with men in four South American cities.
AB  - Conjoint Analysis (CJA), a statistical market-based technique that assesses the
      value consumers place on product characteristics, may be used to predict
      acceptability of hypothetical products. Rectal Microbicides (RM)-substances that
      would prevent HIV infection during receptive anal intercourse-will require
      acceptability data from potential users in multiple settings to inform the
      development process by providing valuable information on desirable product
      characteristics and issues surrounding potential barriers to product use. This
      study applied CJA to explore the acceptability of eight different hypothetical RM
      among 128 MSM in Lima and Iquitos, Peru; Guayaquil, Ecuador; and Rio de Janeiro,
      Brazil. Overall RM acceptability was highest in Guayaquil and lowest in Rio.
      Product effectiveness had the greatest impact on acceptability in all four
      cities, but the impact of other product characteristics varied by city. This
      study demonstrates that MSM from the same region but from different cities place
      different values on RM characteristics that could impact uptake of an actual RM.
      Understanding specific consumer preferences is crucial during RM product
      development, clinical trials and eventual product dissemination.

PMID- 21959987
TI  - The biphasic nature of hypoxia-induced directional migration of activated human
      hepatic stellate cells.
AB  - Liver fibrogenesis is sustained by pro-fibrogenic myofibroblast-like cells (MFs),
      mainly originating from activated hepatic stellate cells (HSC/MFs) or portal
      (myo)fibroblasts, and is favoured by hypoxia-dependent angiogenesis. Human
      HSC/MFs were reported to express vascular-endothelial growth factor (VEGF) and
      VEGF-receptor type 2 and to migrate under hypoxic conditions. This study was
      designed to investigate early and delayed signalling mechanisms involved in
      hypoxia-induced migration of human HSC/MFs. Signal transduction pathways and
      intracellular generation of reactive oxygen species (ROS) were evaluated by
      integrating morphological, cell, and molecular biology techniques. Non-oriented
      and oriented migration were evaluated by using wound healing assay and the
      modified Boyden's chamber assay, respectively. The data indicate that hypoxia
      induced migration of HSC/MFs is a biphasic process characterized by the following
      sequence of events: (a) an early (15 min) and mitochondria-related increased
      generation of intracellular ROS which (b) was sufficient to switch on activation
      of ERK1/2 and JNK1/2 that were responsible for the early phase of oriented
      migration; (c) a delayed and HIF-1alpha-dependent increase in VEGF expression
      (facilitated by ROS) and its progressive, time-dependent release in the
      extracellular medium that (d) was mainly responsible for sustained migration of
      HSC/MFs. Finally, immunohistochemistry performed on HCV-related
      fibrotic/cirrhotic livers revealed HIF-2alpha and haem-oxygenase-1 positivity in
      hepatocytes and alpha-SMA-positive MFs, indicating that MFs were likely to be
      exposed in vivo to both hypoxia and oxidative stress. In conclusion, hypoxia
      induced migration of HSC/MFs involves an early, mitochondrial-dependent ROS
      mediated activation of ERK and JNK, followed by a delayed- and HIF-1alpha
      dependent up-regulation and release of VEGF.

PMID- 21959988
TI  - Hematopoietic recovery kinetics predicts for poor CD34+ cell mobilization after
      cyclophosphamide chemotherapy in multiple myeloma.
AB  - Autologous stem cell transplantation is an important part of therapy in patients
      with multiple myeloma. Some patients fail to collect the desired number of stem
      cells while others require multiple apheresis to reach the desired apheresis
      target. The aim of this study was to determine the predictive factors and if the
      hematopoietic kinetics of recovery were predictive for outcome of stem cell
      mobilization in cyclophosphamide + growth factor (CY-GF) mobilized patients.
      Three hundred and ninety six consecutive CY-GF mobilization attempts between
      January 2000 and December 2009 at Mayo Clinic, Rochester, MN were analyzed.
      Patients were divided into three groups: optimal (>5 * 10(6) CD34/kg), suboptimal
      (2-5 * 10(6) CD34/kg) and poor (<2 * 10(6) /kg CD34+ cells) mobilization groups.
      About 86% of patients had optimal stem cell collection, whereas 8% had suboptimal
      collection and 6% had poor (or failed) collections. Age, Hb, WBC, and platelet
      levels had an impact on mobilization results. Time to peripheral blood (PB)
      CD34+cells >10/MUL predicted for efficiency of collection and the interval
      between recovery of WBC>1 post-CY to PB CD34+ cells>10 was shorter in the optimal
      collection groups. These findings suggest that for patients with a PB CD34+ cell
      count below 10/MUL on Day 13 following CY or 1 day after the WBC>1 * 10(9) /L,
      addition of plerixafor may be helpful to salvage the mobilization attempt.

PMID- 21959989
TI  - Complementary expression and repulsive signaling suggest that EphB receptors and
      ephrin-B ligands control cell positioning in the gastric epithelium.
AB  - Eph receptors and ephrin ligands are membrane-bound cell-cell communication
      molecules with well-defined roles in development. However, their expression and
      functions in the gastric epithelium are virtually unknown. We detected several
      EphB receptors and ephrin-Bs in the gastric corpus mucosa of the adult rodent
      stomach by RT-PCR amplification. Immunostaining showed complementary expression
      patterns, with EphB receptors preferentially expressed in the deeper regions and
      ephrin-Bs in the superficial regions of the gastric units. EphB1, EphB2 and EphB3
      are expressed in mucous neck, chief and parietal cells, respectively. In
      contrast, ephrin-B1 is in pit cells and proliferating cells of the isthmus. In a
      mouse ulcer model, EphB2 expression was upregulated in the regenerating
      epithelium and expanded into the isthmus. Thus, EphB/ephrin-B signaling likely
      occurs preferentially in the isthmus, where receptor-ligand overlap is highest.
      We show that EphB signaling in primary gastric epithelial cells promotes cell
      retraction and repulsion at least in part through RhoA activation. Based on these
      findings, we propose that the EphB-positive progeny of gastric stem cells
      migrates from the isthmus toward the bottom of the gastric glands due to
      repulsive signals arising from contact with ephrin-Bs, which are preferentially
      expressed in the more superficial regions of the isthmus and gastric pits.

PMID- 21959990
TI  - Effect of bacoside extract from Bacopa monniera on physical fatigue induced by
      forced swimming.
AB  - The antifatigue effect of bacoside extract (BME) from Bacopa monniera (L.)
      Wettst. was investigated. Rats were subjected to weight-loaded forced swim test
      (WFST) every alternate day for 3 weeks. The BME at a dosage of 10 mg/kg body
      weight was administered orally to rats for 2 weeks in order to evaluate the
      following biomarkers of physical fatigue: swimming time, change in body weight,
      lipid peroxidation, lactic acid (LA), glycogen, antioxidant enzyme activities
      such as superoxide dismutase (SOD) and catalase (CAT) and blood parameters,
      namely blood urea nitrogen (BUN) and creatine kinase (CK). The exhaustive
      swimming time was increased by 3-fold in the BME supplemented group compared with
      that of the control group on day 13. The BME treatment lowered malondialdehyde
      (MDA) levels in brain, liver and muscle tissues by 11.2%, 16.2% and 37.7%,
      respectively, compared with the control exercised group (p < 0.05). The BME also
      reduced the LA, serum BUN and CK activities significantly compared with that of
      the control. Administration of BME significantly protected the depletion of SOD
      and CAT activities. The HSP-70 expression studies by western blot also confirmed
      the antifatigue property of BME. The present study thus indicates that BME
      ameliorates the various impairments associated with physical fatigue.

PMID- 21959991
TI  - Enzyme-directed assembly and manipulation of organic nanomaterials.
AB  - Enzymes are the prime protagonists in the chemistry of living organisms. As such,
      chemists and biologists have long been fascinated by the array of highly
      selective transformations possible under biological conditions that are
      facilitated by enzyme-catalyzed reactions. Moreover, enzymes are involved in
      replicating, repairing and transmitting information in a highly selective and
      organized fashion through detection and signal amplification cascades. Indeed,
      because of their selectivity and potential for use outside of biological systems,
      enzymes have found immense utility in various biochemical assays and are
      increasingly finding applications in the preparation of small molecules. By
      contrast, the use of enzymatic reactions to prepare and build supramolecular and
      nanoscale materials is relatively rare. In this article, we seek to highlight
      efforts over the past 10 years at taking advantage of enzymatic reactions to
      assemble and manipulate complex soft, organic materials on the nanoscale. It is
      tantalizing to think of these processes as mimics of natural systems where
      enzymes are used in the assembly and transformation of the most complex
      nanomaterials known, for example, virus capsid assemblies and the myriad array of
      nanoscale biomolecular machinery.

PMID- 21959992
TI  - Venom peptide analysis of Vipera ammodytes meridionalis (Viperinae) and Bothrops
      jararacussu (Crotalinae) demonstrates subfamily-specificity of the peptidome in
      the family Viperidae.
AB  - Snake venom peptidomes are valuable sources of pharmacologically active
      compounds. We analyzed the peptidic fractions (peptides with molecular masses <
      10,000 Da) of venoms of Vipera ammodytes meridionalis (Viperinae), the most toxic
      snake in Europe, and Bothrops jararacussu (Crotalinae), an extremely poisonous
      snake of South America. Liquid chromatography/mass spectrometry (LC/MS), direct
      infusion electrospray mass spectrometry (ESI-MS) and matrix-assisted
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) were
      applied to characterize the peptides of both snake venoms. 32 bradykinin
      potentiating peptides (BPPs) were identified in the Crotalinae venom and their
      sequences determined. 3 metalloproteinase inhibitors, 10 BPPs and a Kunitz-type
      inhibitor were observed in the Viperinae venom peptidome. Variability in the C
      terminus of homologous BPPs was observed, which can influence the pharmacological
      effects. The data obtained so far show a subfamily specificity of the venom
      peptidome in the Viperidae family: BPPs are the major peptide component of the
      Crotalinae venom peptidome lacking Kunitz-type inhibitors (with one exception)
      while the Viperinae venom, in addition to BPPs, can contain peptides of the
      bovine pancreatic trypsin inhibitor family. We found indications for a post
      translational phosphorylation of serine residues in Bothrops jararacussu venom
      BPP (S[combining low line]QGLPPGPPIP), which could be a regulatory mechanism in
      their interactions with ACE, and might influence the hypotensive effect. Homology
      between venom BPPs from Viperidae snakes and venom natriuretic peptide precursors
      from Elapidae snakes suggests a structural similarity between the respective
      peptides from the peptidomes of both snake families. The results demonstrate that
      the venoms of both snakes are rich sources of peptides influencing important
      physiological systems such as blood pressure regulation and hemostasis. The data
      can be used for pharmacological and medical applications.

PMID- 21959993
TI  - Role of low-mechanical index CEUS in the differentiation between low and high
      grade bladder carcinoma: a pilot study.

PMID- 21959994
TI  - Determination of hymexazol in cucumber and soil samples by derivatization using
      GC-FPD.
AB  - A sensitive and effective analytical method for the determination of hymexazol in
      cucumber and soil samples by gas chromatography with a flame photometric detector
      was developed. This method was validated with fortified at three different levels
      of 0.2, 1.0 and 5.0 mg/kg. Average recoveries obtained from cucumber and soil
      samples at three fortified levels were 94.0%-107.8% with relative standard
      deviations (RSDs) of less than 11.4%. Limits of quantification (LOQ) in cucumber
      and soil were 0.2 mg/kg. The method was successfully applied to determine
      hymexazol in real samples of cucumber and soil under open fields.

PMID- 21959995
TI  - Type 1 perimedullary arteriovenous fistula with subarachnoid hemorrhage: utility
      of contrast-enhanced 3D gradient-echo technique.
AB  - PURPOSE: In patients with perimedullary arteriovenous fistula (AVF) with
      subarachnoid hemorrhage (SAH), knowledge of lesion location is necessary to
      select the appropriate approach for catheter spinal angiography. We evaluated the
      utility of 3-dimensional (3D) fast imaging with steady-state precession (FISP)
      sequence for detecting type 1 perimedullary AVF with SAH. MATERIALS AND METHODS:
      We evaluated 4 patients (2 men, 2 women, aged 53 to 68 years, mean age, 59.25
      years) with type 1 perimedullary AVF who presented with SAH and underwent
      conventional spin-echo MR and contrast-enhanced 3D FISP imaging. Two
      neuroradiologists assessed detection of vascular lesions and delineation of their
      relationships to the adjacent vessels. Catheter angiography was used as the
      reference standard and compared with the MR findings. RESULTS: Perimedullary AVF
      was located at the medullocervical junction in 2 patients, cervical spine in one,
      and thoracic spine in one. For all patients, use of contrast-enhanced 3D FISP in
      addition to conventional MR imaging improved lesion detection and delineation of
      the relationship between the lesion and surrounding vessels. CONCLUSION: Contrast
      enhanced 3D FISP imaging was useful for detecting and delineating type 1
      perimedullary AVF with SAH.

PMID- 21959996
TI  - Origin of dissolved-phase hyperpolarized 129Xe signal in the mouse chest based on
      experimental evidence from extensive magnetic resonance measurements.
AB  - Pulmonary study using hyperpolarized (HP) (129)Xe gas as an imaging medium must
      focus on dissolved-phase signals to make the most of the characteristic affinity
      of xenon for biological tissues, including blood. However, the spectral pattern
      of these signals differs between mice and other animals, including rats, canines,
      and humans. Dissolved-phase study has been reported only scarcely in mice, so
      spectral assignment has been an important subject for HP (129)Xe magnetic
      resonance (MR) spectroscopy (MRS) and MR imaging for its wider application. We
      performed MRS, including magnetization transfer experiments, and MR imaging
      studies to confirm the origin of dissolved-phase signals of mice ex vivo and in
      vivo and obtained evidence to assign dissolved-phase signals at 192 ppm for
      epicardial fat, 196 ppm for lung parenchyma, and 200 ppm for blood. These results
      were the first to show the possibility of fast exchange of xenon between plasma
      and red blood cells.

PMID- 21959997
TI  - Tumor enhancement effect of overexpressed manganese-superoxide dismutase in
      manganese-enhanced MR imaging.
AB  - PURPOSE: Manganese-enhanced magnetic resonance imaging (MEMRI), used to trace
      neuronal connections and visualize brain activity, has recently been suggested
      useful for tumor detection, but the mechanism of tumor enhancement by manganese
      (Mn) is poorly understood. Our recent report of preferential enhancement of human
      mesothelioma cells with higher levels of manganese-superoxide dismutase (Mn-SOD)
      expression may suggest a correlation between Mn-SOD expression and enhancement.
      We investigate this possibility further using engineered human ovarian cancer
      cells overexpressing Mn-SOD. METHODS: We subcutaneously implanted SK-OV-3 human
      ovarian cancer cells stably overexpressing Mn-SOD (SK-Mn-SOD) into athymic nude
      mice and SK-OV-3 cells with plasmid DNAs carrying neomycin-resistant genes (SK
      neo) into the same mice for controls. We conducted MEMRI in the tumor-bearing
      mice and compared enhancement between the 2 tumors. RESULTS: Subcutaneous SK-Mn
      SOD tumors were preferentially enhanced in MEMRI compared to SK-neo tumors. After
      Mn enhancement, the T(1)-relaxation rate (R(1)=1/T(1)) increased significantly
      for SK-Mn-SOD but not SK-neo tumors. CONCLUSION: In some tumors, high expression
      of Mn-SOD may be a biological factor responsible for enhanced signal in MEMRI.

PMID- 21959998
TI  - High resolution NMR imaging using a high field yokeless permanent magnet.
AB  - We measured the homogeneity and stability of the magnetic field of a high field
      (about 1.04 tesla) yokeless permanent magnet with 40-mm gap for high resolution
      nuclear magnetic resonance (NMR) imaging. Homogeneity was evaluated using a 3
      dimensional (3D) lattice phantom and 3D spin-echo imaging sequences. In the
      central sphere (20-mm diameter), peak-to-peak magnetic field inhomogeneity was
      about 60 ppm, and the root-mean-square was 8 ppm. We measured room temperature,
      magnet temperature, and NMR frequency of the magnet simultaneously every minute
      for about 68 hours with and without the thermal insulator of the magnet. A simple
      mathematical model described the magnet's thermal property. Based on magnet
      performance, we performed high resolution (up to [20 um](2)) imaging with
      internal NMR lock sequences of several biological samples. Our results
      demonstrated the usefulness of the high field small yokeless permanent magnet for
      high resolution NMR imaging.

PMID- 21959999
TI  - Protective effect of hydrogen-rich water against gentamicin-induced
      nephrotoxicity in rats using blood oxygenation level-dependent MR imaging.
AB  - PURPOSE: We assessed intrarenal oxygenation in gentamicin-induced nephrotoxicity
      (GIN) and the protective effect of hydrogen-rich water (HW) against GIN using
      blood oxygenation level-dependent magnetic resonance (MR) imaging. MATERIALS AND
      METHODS: We acquired T(2)*-weighted images (T(2)*WI) of 21 rats on Days 0, 2, 4,
      and 7 using a 1.5-tesla MR imaging system. The rats were divided into 3 groups of
      seven each: control rats had free access to standard water and no gentamicin (GM)
      injection; rats designated the GM group had free access to standard water and
      were injected with GM (80 mg/kg/day) subcutaneously for 7 days; and the third
      group, designated the GM+HW group, had free access to HW and were injected with
      GM. R(2)* (=1/T(2)*) was estimated from T(2)*WI. RESULTS: R(2)* values in the
      cortex were significantly decreased on Days 2, 4, and 7 compared with those on
      Day 0 in the GM group but not significantly changed in the control and GM+HW
      groups. R(2)* values in the medulla did not change significantly in any group.
      CONCLUSIONS: Our findings suggested reduced oxygen utility, mainly in the cortex,
      in gentamicin-induced nephrotoxicity and an ameliorative effect of hydrogen-rich
      water against GIN.

PMID- 21960000
TI  - Temperature dependence of relaxation times in proton components of fatty acids.
AB  - We examined the temperature dependence of relaxation times in proton components
      of fatty acids in various samples in vitro at 11 tesla as a standard calibration
      data for quantitative temperature imaging of fat. The spin-lattice relaxation
      time, T(1), of both the methylene (CH(2)) chain and terminal methyl (CH(3)) was
      linearly related to temperature (r>0.98, P<0.001) in samples of animal fat. The
      temperature coefficients for the 2 primary proton components differed
      significantly; in 5 bovine fat samples, the coefficient at 30  degrees C was
      1.79+/-0.07 (%/ degrees C) for methylene and 2.98+/-0.38 (%/ degrees C) for
      methyl. Numerical simulations based on such a difference demonstrated the
      possibility of considerable error from inconsistent ratios in fatty acid
      components when calibrating and estimating temperature. The error reached 3.3 
      degrees C per 15  degrees C in temperature elevation when we used a pure CH(2)
      signal for calibration and observed the signal with 18% of CH(3) to estimate
      temperature. These findings suggested that separating the fatty acid components
      would significantly improve accuracy in quantitative thermometry for fat. Use of
      the T(1) of CH(2) seems promising in terms of reliability and reproducibility in
      measuring temperature of fat.

PMID- 21960001
TI  - Detection of active plaques in multiple sclerosis using susceptibility-weighted
      imaging: comparison with gadolinium-enhanced MR imaging.
AB  - PURPOSE: Susceptibility-weighted (SW) imaging is a magnetic resonance (MR)
      imaging technique reported effective in visualizing multiple sclerosis (MS)
      plaques, but its capacity to distinguish active plaques remains unclear. We
      evaluated active plaque detection by SW compared with contrast-enhanced MR
      imaging. METHODS: We prospectively examined 11 patients using a 3-tesla scanner.
      Two neuroradiologists independently evaluated signal changes of plaques and
      accompanying low signal rims in 74 plaques on various SW images (magnitude,
      phase, and minimum intensity projection [minIP]), and on contrast-enhanced T(1)
      weighted images (T(1)WI). We correlated signal alterations on various SW images
      and contrast enhancement on T(1)WI using Fisher's exact test and calculated
      sensitivity and specificity for predicting gadolinium enhancement. RESULTS: Only
      changes in plaque signal on SW magnitude images correlated significantly with
      contrast enhancement of the plaques (P=0.008), and high signal intensity had
      0.556 sensitivity and 0.787 specificity for predicting contrast-enhanced plaques.
      Furthermore, plaques with rims of low signal showed sensitivity of 0.296 and
      specificity of 0.957. CONCLUSIONS: Susceptibility-weighted magnitude, but not
      phase or minIP, images can predict MS plaques with contrast enhancement with high
      specificity.

PMID- 21960002
TI  - Contrast enhancement of the anterior eye segment and subarachnoid space:
      detection in the normal state by heavily T2-weighted 3D FLAIR.
AB  - PURPOSE: Fluid-attenuated inversion recovery (FLAIR) has been reported more
      sensitive than T(1)-weighted images in detecting low concentration gadolinium
      based contrast media (GBCM) in fluid, and heavily T(2)-weighted (hT(2)W) 3
      dimensional (3D) FLAIR has recently been reported even more sensitive than
      conventional 3D FLAIR. We investigated whether high signal of the anterior eye
      segment (AES) and subarachnoid space (SAS) in various locations as well as
      cerebrospinal fluid (CSF) in cisterns and ventricles can be detected on hT(2)W 3D
      FLAIR images obtained 4 hours after intravenous administration of GBCM in
      subjects without eye and SAS diseases. METHODS: Ten patients suspected of having
      Meniere's disease underwent hT(2)W 3D FLAIR 4 hours after intravenous
      administration of single-dose GBCM to evaluate endolymphatic hydrops. We
      evaluated signal intensity of AES, SAS surrounding the optic nerve, SAS in
      Meckel's cave, CSF in the internal auditory canal, CSF in the prepontine cistern,
      CSF in the lateral and fourth ventricles, and lymph fluid in the cochlea by
      comparison with non-contrast images obtained in a separate group of 5 patients.
      The signal intensity of each structure was normalized by that of the pontine
      parenchyma. RESULTS: We observed no signal difference in images of the pontine
      parenchyma obtained before and after enhancement. Significant signal difference
      was seen in all structures except the lateral and fourth ventricles. CONCLUSION:
      Four hours after intravenous injection, GBCM can be detected by hT(2)W 3D FLAIR
      in various fluid-containing spaces, such as the AES and various SAS and CSF
      spaces.

PMID- 21960003
TI  - Papillary renal cell carcinoma with extensive paraaortic nodal metastasis
      mimicking malignant lymphoma.
AB  - A 52-year-old woman with abdominal distension underwent computed tomography (CT)
      that demonstrated extensive paraaortic lymphadenopathy and a right renal mass.
      Compared to the renal cortex, the lesions exhibited low signal intensity on T(1)-
      and T(2)-weighted images and high intensity on diffusion-weighted magnetic
      resonance (MR) images. We suspected malignant lymphoma and performed excisional
      biopsy, which revealed metastatic papillary renal cell carcinoma.
      Retrospectively, significantly reduced signal on in-phase chemical shift MR
      images compared to out-of-phase images suggested the presence of intratumoral
      hemosiderin, a characteristic finding of this entity.

PMID- 21960004
TI  - Primary carcinoid tumor of the ovary: MR imaging characteristics with pathologic
      correlation.
AB  - Ovarian carcinoid tumor is a rare neoplasm that may appear as a solid mass or
      often combined with teratomas or mucinous tumors. We report 2 cases associated
      with mucinous cystadenomas and describe their magnetic resonance imaging
      characteristics. On T(2)-weighted images, the tumors appeared as multilocular
      cystic masses with hypointense solid components as a result of abundant fibrous
      stroma induced by serotonin. Demonstration of prominent hypervascularity of the
      tumors following contrast administration on dynamic study may be the clue to
      differential diagnosis.

PMID- 21960005
TI  - PPM1A dephosphorylates RanBP3 to enable efficient nuclear export of Smad2 and
      Smad3.
AB  - Smad2 and Smad3 (Smad2/3) are essential signal transducers and transcription
      factors in the canonical transforming growth factor-beta (TGF-beta) signalling
      pathway. Active Smad2/3 signalling in the nucleus is terminated by
      dephosphorylation and subsequent nuclear export of Smad2/3. Here we report that
      protein phosphatase PPM1A regulates the nuclear export of Smad2/3 through
      targeting nuclear exporter RanBP3. PPM1A directly interacted with and
      dephosphorylated RanBP3 at Ser 58 in vitro and in vivo. Consistently, RanBP3
      phosphorylation was elevated in PPM1A-null mouse embryonic fibroblasts.
      Dephosphorylation of RanBP3 at Ser 58 promoted its ability to export Smad2/3 and
      terminate TGF-beta responses. Our findings indicate the critical role of PPM1A in
      maximizing exporter activity of RanBP3 for efficient termination of canonical TGF
      beta signalling.

PMID- 21960006
TI  - Nucleolar protein Spindlin1 recognizes H3K4 methylation and stimulates the
      expression of rRNA genes.
AB  - The tandem Tudor-like domain-containing protein Spindlin1 has been reported to be
      a meiotic spindle-associated protein. Here we report that Spindlin1 is not
      associated with the spindle in mouse embryonic fibroblast cells during mitotic
      divisions. In interphase cells, Spindlin1 specifically localizes to the nucleoli.
      Moreover, Spindlin1 is a histone methylation effector protein that specifically
      recognizes H3K4 methylation. Finally, Spindlin1 localizes to the active ribosomal
      DNA (rDNA) repeats, and Spindlin1 facilitates the expression of rRNA genes.

PMID- 21960007
TI  - Analysis of substrate specificity of Schizosaccharomyces pombe Mag1 alkylpurine
      DNA glycosylase.
AB  - DNA glycosylases specialized for the repair of alkylation damage must identify,
      with fine specificity, a diverse array of subtle modifications within DNA. The
      current mechanism involves damage sensing through interrogation of the DNA
      duplex, followed by more specific recognition of the target base inside the
      active site pocket. To better understand the physical basis for alkylpurine
      detection, we determined the crystal structure of Schizosaccharomyces pombe Mag1
      (spMag1) in complex with DNA and performed a mutational analysis of spMag1 and
      the close homologue from Saccharomyces cerevisiae (scMag). Despite strong
      homology, spMag1 and scMag differ in substrate specificity and cellular
      alkylation sensitivity, although the enzymological basis for their functional
      differences is unknown. We show that Mag preference for 1,N(6)-ethenoadenine (EA)
      is influenced by a minor groove-interrogating residue more than the composition
      of the nucleobase-binding pocket. Exchanging this residue between Mag proteins
      swapped their EA activities, providing evidence that residues outside the
      extrahelical base-binding pocket have a role in identification of a particular
      modification in addition to sensing damage.

PMID- 21960008
TI  - Heterogenous mechanisms of mild cognitive impairment in Parkinson's disease.
AB  - Mild cognitive impairment in Parkinson disease (PD-MCI) shows heterogeneity in
      the clinical presentation, neuropsychology, neuroimaging, and neuropathology,
      suggesting abnormal metabolic network activities involving several cortical and
      subcortical systems. Prospective studies using specific biomarkers, including
      amyloid imaging and CSF biomarkers are important for the diagnosis and prognostic
      assessment of early cognitive deficits in PD patients.

PMID- 21960010
TI  - Screening structure-property correlations and device performance of Ir(III)
      complexes in multi-layer PhOLEDs.
AB  - The structure-property correlations of a set of heteroleptic red- and green
      emitting Ir(III) complexes with different temperature sensitivities and charge
      trapping capabilities are described, revealing superb performance in multi-layer
      phosphorescent organic light-emitting diodes (PhOLEDs) expressed by very high
      maximum luminous efficiencies up to 36.8 cd A(-1). Using 2-phenylpyridine and
      with 2-(naphthalen-1-yl)pyridine as the C^N ligand, the resulting red emitting
      complex featured a maximum luminous efficiency of 10.8 cd A(-1); one of the most
      excellent device performances within this class of red Ir(III) emitters.

PMID- 21960009
TI  - A53T-alpha-synuclein-overexpression in the mouse nigrostriatal pathway leads to
      early increase of 14-3-3 epsilon and late increase of GFAP.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder frequent at old age
      characterized by atrophy of the nigrostriatal projection. Overexpression and A53T
      mutation of the presynaptic, vesicle-associated chaperone alpha-synuclein are
      known to cause early-onset autosomal dominant PD. We previously generated mice
      with transgenic overexpression of human A53T-alpha-synuclein (A53T-SNCA) in
      dopaminergic substantia nigra neurons as a model of early PD. To elucidate the
      early and late effects of A53T-alpha-synuclein on the proteome of dopaminergic
      nerve terminals in the striatum, we now investigated expression profiles of young
      and old mice using two-dimensional fluorescence difference in gel electrophoresis
      (2D-DIGE) and mass spectrometry. In total, 15 proteins were upregulated and 2
      downregulated. Mice before the onset of motor anomalies showed an upregulation of
      the spot containing 14-3-3 proteins, in particular the epsilon isoform, as well
      as altered levels of chaperones, vesicle trafficking and bioenergetics proteins.
      In old mice, the persistent upregulation of 14-3-3 proteins was aggravated by an
      increase of glial fibrillary acidic protein (GFAP) suggesting astrogliosis due to
      initial neurodegeneration. Independent immunoblots corroborated GFAP upregulation
      and 14-3-3 upregulation for the epsilon isoform, and also detected significant
      eta and gamma changes. Only for 14-3-3 epsilon a corresponding mRNA increase was
      observed in midbrain, suggesting it is transcribed in dopaminergic perikarya and
      accumulates as protein in presynapses, together with A53T-SNCA. 14-3-3 proteins
      associate with alpha-synuclein in vitro and in pathognomonic Lewy bodies of PD
      brains. They act as chaperones in signaling, dopamine synthesis and stress
      response. Thus, their early dysregulation probably reflects a response to alpha
      synuclein toxicity.

PMID- 21960011
TI  - Genetic variants in interferon gamma (IFN-gamma) gene are associated with
      resistance against ticks in Bos taurus and Bos indicus.
AB  - In tropical and subtropical regions of the world, parasitic diseases are major
      obstacle in the health and ultimately overall performance of animals. Cattle
      express heritable, contrasting phenotypes when exposed to ticks depicting genetic
      nature of trait. IFN-gamma is one of the most reported genes critical for innate
      and adaptive immunity against viral and intracellular infections. To identify its
      role in resistance for ectoparasite especially tick, genetic characterization of
      this gene was done in resistant and susceptible animals of Sahiwal cattle (n =
      95) and Friesian (n = 92). Nine Polymorphisms were identified, three of them were
      found in exonic region. One out of nine variants was being reported previously
      (ss82716193) and was confirmed in Pakistani Sahiwal cattle population as well.
      Single site analysis of each variant depicted their significance in tick
      resistant and tick susceptible groups (P < 0.05). The associations using
      haplotypes were more informative than for single markers. Eighteen different
      haplotypes resulting from nine polymorphic sites were used in construction of
      maximum parsimony tree which categorized resistant and susceptible animals in two
      clades. Genetic markers identified in this study can be useful in future breeding
      selection programs against tick resistance.

PMID- 21960012
TI  - Genetic association of phosphodiesterase 1B (PDE1B) with carcass traits in Korean
      cattle.
AB  - Quantitative trait loci for fat deposition and carcass traits have been
      identified in the vicinity of the gene encoding phosphodiesterase 1B (PDE1B) on
      bovine chromosome 5. Therefore, the PDE1B gene can be considered as a positional
      and functional candidate gene for carcass traits in beef cattle. This study aimed
      to identify single nucleotide polymorphisms (SNPs) in the PDE1B gene and to
      evaluate their associations with carcass traits in Korean cattle. Eight SNPs,
      g.440T>G, g.17122A>G, g.17507A>C, g.17575A>G, g.17607T>C, g.17609C>A, g.17692C>T,
      and g.17707C>G, were identified in the region ranged from exon 1 to intron 6.
      Five of them were used for association analysis because of their availability of
      restriction fragment length polymorphisms. As a result, g.17122A>G in intron 3
      was significantly associated with backfat thickness (BFT), and g.17507A>C in exon
      5 was associated with longissimus dorsi muscle area (LMA, P < 0.05). Animals with
      the AG genotype of g.17122 had thicker BFT than those with the AA genotype.
      Animals with the AA or AC genotype of g.17507A>C had larger LMA than those with
      the CC genotype. We suggested the PDE1B gene as a candidate gene for carcass
      traits of beef cattle. Fine mapping would be required for application to marker
      assisted selection.

PMID- 21960013
TI  - Reproducibility of 3D 1H MR spectroscopic imaging of the prostate at 1.5T.
AB  - PURPOSE: To determine the reproducibility of 3D proton magnetic resonance
      spectroscopic imaging ((1)H-MRSI) of the human prostate in a multicenter setting
      at 1.5T. MATERIALS AND METHODS: Fourteen subjects were measured twice with 3D
      point-resolved spectroscopy (PRESS) (1)H-MRSI using an endorectal coil. MRSI
      voxels were selected in the peripheral zone and combined central gland at the
      same location in the prostate in both measurements. Voxels with approved spectral
      quality were included to calculate Bland-Altman parameters for reproducibility
      from the choline plus creatine to citrate ratio (CC/C). The repeated
      spectroscopic data were also evaluated with a standardized clinical scoring
      system. RESULTS: A total of 74 voxels were included for reproducibility analysis.
      The complete range of biologically interesting CC/C ratios was covered. The
      overall within-voxel standard deviation (SD) of the CC/C ratio of the repeated
      measurements was 0.13. This value is equal to the between-subject SD of noncancer
      prostate tissue. In >90% of the voxels the standardized clinical score did not
      differ relevantly between the measurements. CONCLUSION: Repeated measurements of
      in vivo 3D (1)H-MRSI of the complete prostate at 1.5T produce equal and
      quantitative results. The reproducibility of the technique is high enough to
      provide it as a reliable tool in assessing tumor presence in the prostate.

PMID- 21960014
TI  - Constitutive and dark-induced expression of Solanum tuberosum phosphoenolpyruvate
      carboxylase enhances stomatal opening and photosynthetic performance of
      Arabidopsis thaliana.
AB  - The effect of constitutive and dark-induced expression of Solanum tuberosum
      phosphoenolpyruvate carboxylase (PEPC) on the opening state of stomata and
      photosynthetic performance in Arabidopsis thaliana plants was studied. Transcript
      accumulation analyses of the A. thaliana dark-induced (Din10 and Din6) and the
      Pisum sativum asparagine synthetase 2 promoters (Asn2) in transiently transformed
      tobacco leaves showed that Din10 promoter induced more DsRed accumulation in the
      dark compared to the other din genes. Overexpression of PEPC under the control of
      the constitutive enhanced CaMV 35S (p35SS) and dark-induced Din10 promoter in
      stably transformed A. thaliana plants increased the number of opened stomata in
      dark adapted leaves. Gas exchange measurements using A. thaliana plants
      transgenic for p35SS-PEPC and Din10-PEPC revealed a marked increase in stomatal
      conductance, transpiration, and dark respiration rates measured in the dark
      compared to wild-type plants. Moreover, measurement of CO(2) assimilation rates
      at different external CO(2) concentrations (C(a) ) and different light
      intensities shows an increase in the CO(2) assimilation rates in transgenic
      Arabidopsis lines compared to wild-type plants. This is considered as first step
      towards transferring the aspects of Crassulacean acid metabolism-like
      photosynthetic mechanism into C3 plants.

PMID- 21960015
TI  - Paracoccus oceanense sp. nov., isolated from the West Pacific.
AB  - A Gram-negative, short ovoid- to coccus-shaped, aerobic, motile, non-spore
      forming bacterium (designated strain JLT1679(T)) was isolated from West Pacific.
      Cells have subpolar flagella, dividing by binary fission. Phylogenetic analyses
      based on 16S rRNA gene sequences showed that the strain belongs to branch of the
      evolutionary radiation occupied by the genus Paracoccus, family Rhodobacteraceae,
      order Rhodobacterales, class Alphaproteobacteria. The closest neighbours were
      Paracoccus stylophorae KTW-16(T) (97.1% similarity), Paracoccus caeni strain
      MJ17(T) (96.5% similarity), Paracoccus homiensis DD-R11(T) (96.0% similarity) and
      Paracoccus alcaliphilus JCM 7364(T) (95.8% similarity). The predominant cellular
      fatty acids of strain JLT1679(T) were summed feature 8 (18:1omega6c) (38.8%),
      C(18:0) (27.7%), C(16:0) (22.5%), and significant amounts of C(18:1) omega9c
      (5.1%), C(14:0) (3.8%) and C(18:1) omega7c 11-methyl (2.1%), were present. The
      predominant respiratory ubiquinone of strain JLT1679(T) was Q-10 and the DNA G +
      C content of strain JLT1679(T) was 59.5 mol%. The polar lipid profile consisted
      of a mixture of phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine
      and sphingoglycolipid. The isolate was distinguishable from members of the genus
      Paracoccus on the basis of phenotypic and biochemical characteristics. It is
      evident from the genotypic, chemotaxonomic and phenotypic data that strain
      JLT1679(T) represents a novel species of the genus Paracoccus, for which the name
      Paracoccus oceanense sp. nov. is proposed. The type strain is JLT1679(T) (= JCM
      17768(T) = CGMCC 1.10831(T)).

PMID- 21960016
TI  - Pathway for degradation of 2-chloro-4-nitrophenol in Arthrobacter sp. SJCon.
AB  - Degradation of 2-Chloro-4-nitrophenol (2C4NP) was studied by Arthrobacter sp.
      SJCon, isolated from the soil of a pesticide contaminated site. This strain
      utilized 2C4NP as sole source of carbon and energy and degraded 2C4NP with
      stoichiometric release of nitrite and chloride ions. A metabolite was detected
      during the study of 2C4NP degradation and identified as chlorohydroquinone (CHQ)
      by thin layer chromatography (TLC), high performance liquid chromatography
      (HPLC), and gas chromatography-mass spectrometry (GC-MS). Inhibition study using
      2,2'-dipyridyl showed that CHQ is a terminal aromatic compound in degradation
      pathway of 2C4NP. CHQ dioxygenase activity was observed in the crude extract of
      2C4NP induced cells of the strain SJCon that suggested the cleavage of the CHQ to
      maleylacetate (MA). Our study clearly showed that Arthrobacter sp. SJCon degraded
      2C4NP via formation of CHQ that further cleaved to MA by CHQ dioxygenase. This
      mechanism of degradation of 2C4NP differs from previously reported degradation
      pathways of 2C4NP.

PMID- 21960017
TI  - Internet use and eHealth literacy of low-income parents whose children have
      special health care needs.
AB  - BACKGROUND: The Internet has revolutionized the way in which many Americans
      search for health care information. Unfortunately, being able to use the Internet
      for this purpose is predicated on having access to the Internet and being able to
      understand and comprehend online health information. This is especially important
      for parents of children with special health care needs who are forced to make
      many medical decisions throughout the lives of their children. Yet, no
      information is available about this vulnerable group. OBJECTIVE: For parents of
      children with special health care needs we sought to (1) describe their Internet
      access and use, (2) determine which child and household factors were associated
      with Internet use, (3) describe eHealth literacy of Internet users, and (4)
      determine which child and household factors were associated with greater eHealth
      literacy. METHODS: This was a cross-sectional telephone survey of 2371 parents
      whose children with special health care needs were enrolled in Florida's Medicaid
      and State Children's Health Insurance Plan (SCHIP) programs (4072 parents were
      approached). To be enrolled in the program, families must have incomes that are
      less than or equal to 200% of the federal poverty level. The eHealth Literacy
      Scale (eHEALS) was used to measure eHealth literacy. Descriptive and multivariate
      analyses were conducted to address the study objectives. RESULTS: The survey
      response rate was 58.2%. Participating parents were mainly female (2154/2371,
      91%), white non-Hispanic (915/2371, 39%), English speaking (1827/2371, 77%), high
      school graduates (721/2371, 30%), married (1252/2371, 53%), and living in a two
      parent household (1212/2371, 51%). Additionally, 82% of parents (1945/2371) in
      the sample reported that they used the Internet, and 49% of those parents used it
      daily (1158/2371). Almost three-quarters of Internet users had access to the
      Internet at home while about one-half had access at work. Parents who were
      African American, non-English speaking, older, and not college graduates were
      less likely to use the Internet than their referent groups (P < .001). About 74%
      of Internet users (1448/1945) reported that they knew how to find health
      information for their children. However, only about one-half (1030/1945) reported
      that they can tell high quality from low quality resources online or that they
      feel confident in using information accessed online to make health decisions.
      Multivariate regression results consistently showed that being a non-English
      speaker, having less than a high school education, and being older were all
      significantly associated with lower eHealth literacy (all P < .001). CONCLUSION:
      Low-income parents of children with special health care needs have access to and
      use the Internet as a source of information about their children's health.
      However, some parents are unable to distinguish between high and low quality
      information and are not confident in using the Internet. This information is
      timely because as the pressure to use the Internet to empower consumers and
      exchange information increases, issues related to access and disparities must be
      better understood.

PMID- 21960018
TI  - Mapping the nanoparticle-coating monolayer with NMR pseudocontact shifts.
AB  - Lanthanide ions Yb(3+) and Tb(3+), once bound to the monolayer of organic
      molecules coating the surface of gold nanoparticles, induce pseudo-contact shifts
      on the signals of nearby nuclear spins. This not only allows the investigation of
      the average structure of the ligands in the monolayer but also the mapping of the
      position of organic molecules bound to it.

PMID- 21960019
TI  - Quantum instanton calculation of rate constants for the C2H6 + H -> C2H5 + H2
      reaction: anharmonicity and kinetic isotope effects.
AB  - Thermal rate constants and kinetic isotope effects for the title reaction are
      calculated by using the quantum instanton approximation within the full
      dimensional Cartesian coordinates. The obtained results are in good agreement
      with experimental measurements at high temperatures. The detailed investigation
      reveals that the anharmonicity of the hindered internal rotation motion does not
      influence the rate too much compared to its harmonic oscillator approximation.
      However, the motion of the nonreactive methyl group in C(2)H(6) significantly
      enhances the rates compared to its rigid case, which makes conventional reduced
      dimensionality calculations a challenge. In addition, the temperature dependence
      of kinetic isotope effects is also revealed.

PMID- 21960020
TI  - Li insertion in ball-milled graphitic carbon studied by total x-ray diffraction.
AB  - Ball-milled graphitic carbon, both not and electrochemically lithiated, has been
      studied by total x-ray diffraction involving high-energy synchrotron radiation
      scattering and atomic pair distribution function analysis. The experimental data
      has been used to guide reverse Monte Carlo simulations of the three-dimensional
      structure of the not-lithiated samples. Experimental and modeling results show
      that ball milling for short times breaks the graphitic layers into smaller pieces
      as well as generates extended atomic vacancies. Those increase the overall
      ability of the material to accommodate lithium. Ball milling for longer times
      keeps generating even more atomic vacancies in the graphitic layers. Carbon atoms
      displaced from the layers, however, move in between the layers, turning heavily
      ball-milled graphitic carbon into an assembly of almost-fused-together, heavily
      buckled layers that have an impaired ability to accommodate Li atoms. This helps
      explain well the initial substantial increase and then decrease in the Li storage
      capacity of ball-milled graphitic carbon. The study demonstrates the great
      ability of total x-ray diffraction to provide precise structural information for
      complex materials that are being increasingly explored for energy applications.

PMID- 21960021
TI  - Mechanisms underlying somatostatin receptor 2 down-regulation of vascular
      endothelial growth factor expression in response to hypoxia in mouse retinal
      explants.
AB  - Hypoxia is a trigger of VEGF expression, the primary cause of retinal pathologies
      characterized by neovascularization. During hypoxia, transcription factors such
      as STAT3 and HIF-1 promote the increase in VEGF expression. Octreotide, a
      somatostatin receptor 2 (sst(2) )-preferring agonist, reduces retinal VEGF
      expression and neovascularization. To investigate the intracellular pathways
      linking sst(2) activation to the inhibition of hypoxia-induced VEGF up
      regulation, we used pharmacological approaches and siRNA in mouse retinal
      explants cultured in normoxia or hypoxia. In hypoxic explants in which STAT3 or
      HIF-1 was inhibited, we observed the existence of reciprocal interactions between
      STAT3 and HIF-1, which synergistically induced VEGF expression. Octreotide
      prevented hypoxia-induced activation of STAT3 and HIF-1, and the downstream
      increase in VEGF expression, as evaluated in hypoxic explants treated with
      pharmacological inhibitors of STAT3 or HIF-1 and in normoxic explants in which
      pharmacological activators of STAT3 or HIF-1 were used to mimic a hypoxia-like
      response. The effect of octreotide on STAT3 activation is in part indirect,
      through the blockade of VEGFR-2 phosphorylation. The effect of octreotide on
      STAT3, HIF-1, VEGFR-2, and VEGF required Src homology region 2 domain-containing
      phosphatase 1 (SHP-1). In hypoxic extracts, octreotide induced SHP-1
      phosphorylation and activation, and inhibiting SHP-1 abolished the octreotide
      effect on STAT3, HIF-1, VEGFR-2, and VEGF. The central role of SHP-1 in the
      modulation of STAT3 and HIF-1 was confirmed in normoxic explants in which
      pharmacologically activated SHP-1 prevented the effect of STAT3 or HIF-1
      activation. Immunohistochemical studies showed that under hypoxia sst(2) and VEGF
      are expressed by retinal vessels, thus indicating a possible direct effect of
      octreotide on VEGF-containing endothelial cells. These data clarify the mechanism
      by which octreotide prevents hypoxia-induced VEGF up-regulation and support the
      effectiveness of octreotide in treatment of oxygen-induced retinopathies. These
      results may have implications in designing therapies targeting STAT3 and/or HIF-1
      aimed at preventing retinal neovascularization.

PMID- 21960022
TI  - Worse than feared? Failure induction modulates the electrophysiological signature
      of error monitoring during subsequent learning.
AB  - This study examined how self-relevant failure influences error monitoring--as
      reflected in the error-related negativity (Ne/ERN) --and behavioral adaptation
      during subsequent feedback-based learning. We applied two phases (pre- and
      posttest) of a probabilistic learning task. Between pre- and posttest,
      participants were assigned to one of two groups receiving either failure feedback
      or no feedback during a visual search task described as diagnostic of
      intellectual abilities. To disentangle the effects of failure and motivational
      disengagement due to prolonged task performance, we linked the posttest to
      intelligence (Experiment 1) or described it in neutral terms (Experiment 2).
      Failure induction was associated with an increase in Ne/ERN amplitude at posttest
      in both experiments, although there were no differences in overall performance.
      In contrast, the Ne/ERN decreased from pre- to posttest in the no-failure
      feedback group, particularly in Experiment 2. Furthermore, failure feedback
      affected error-related behavioral adjustments, suggesting a shift toward a
      reactive, error-driven mode of behavior control. These findings emphasize the
      importance of affective-motivational state in error processing and subsequent
      behavioral adaptation.

PMID- 21960023
TI  - MRI study of cryoinjury infarction in pig hearts: i. Effects of intrapericardial
      delivery of bFGF/VEGF embedded in alginate beads.
AB  - The aim of the study was the testing of sustained intrapericardial delivery of
      vascular growth factors (GFs) from alginate beads on cryoinjury size and
      perfusion. In domestic pigs (15-20 kg, n = 21), the left ventricular (LV)
      anterolateral wall of exposed hearts was cryoinjured using an aluminum rod (25 mm
      o.d.) cooled in liquid nitrogen. Alginate beads (d = 3.2 +/- 0.2 mm), containing
      human recombinant basic fibroblast GF (bFGF, 50 ug) and vascular endothelial GF
      (VEGF, 50 ug) + heparin (50 ug) or heparin alone (Con, n = 5), were sutured to
      the cryoinjured epicardium (GF, n = 5; Con, n = 3 ) or pericardium (GF, n = 3;
      Con, n = 2), or no beads were implanted (n = 4). Four pigs were sham-operated.
      Cine and T(1) -weighted MRI was performed in vivo at ~2.5 h and 1, 2, 3 and 4
      weeks after injury in a 3T imager. A double bolus of GdDTPA was injected (0.05
      and 0.15 mmol/kg) and first-pass and late enhancement kinetics were monitored.
      After 4-week cryoinjury, following the injection of 5 x 10(6) 15-um NIR
      fluorescent microspheres (FMS, 645/680 nm), hearts were sliced and examined with
      fluorescence imaging. Triphenyltetrazolium chloride (TTC) staining was used to
      determine infarct areas. Epicardial GF-containing beads were encapsulated within
      the hypointense 3-4-week infarct tissue. This tissue had a 75% higher LV
      thickening index, a lower distribution volume for GdDTPA (0.44 +/- 0.12 vs 0.68
      +/- 0.05, p = 0.02), and 25% faster first-pass Gd kinetics relative to control
      infarctions. TTC staining revealed TTC-positive islands in the core of treated
      infarcts, which showed higher FMS fluorescence relative to surrounding infarct
      tissue (0.64 +/- 0.14 vs. 0.31 +/- 0.14; p < 0.0001) and to control infarcts
      (0.37 +/- 0.09, p < 0.05). GF-beads attached to the pericardium were not
      effective. We conclude that sustained intrapericardial release of bFGF + VEGF
      from alginate beads attached to the epicardium facilitated vascular growth in the
      cryoinjured area.

PMID- 21960024
TI  - Balloon kyphoplasty improves back pain but does not result in a permanent
      realignment of the thoracolumbar spine.
AB  - INTRODUCTION: Balloon kyphoplasty (BKP) has been established as a standard
      procedure for treatment of osteoporotic compression fractures of the spine in
      elderly patients, as it results in pain relief for most of the patients.
      Moreover, BKP may result in a partial realignment of the sagittal shape of the
      vertebra and the spine. However, it is unclear whether BKP may result in long
      term improvement of the sagittal alignment of the spine. The aim of the current
      study was to investigate if there is a significant loss of correction of the
      sagittal alignment of the thoracolumbar spine following BKP. METHODS: A
      prospective, noncontrolled, nonrandomized study, consisting of 71 patients
      treated for single level osteoporotic compression fracture by BKP at 1
      institution and by 1 surgeon, was done. We checked the following radiographic
      outcome parameters: Beck's ratio, the kyphosis angle of the treated vertebra, the
      angle of kyphosis including the treated vertebra and the adjacent disc
      (monosegmental angle), the angle of kyphosis, including the treated segment, the
      adjacent disc as well as the adjacent vertebra (bisegmental angle). RESULTS: BKP
      resulted in significant pain relief with a score decreasing from 7.11 to 1.73 on
      a visual analogue scale immediately after the procedure. The effekt persisted
      after 1 year with a score of 1.58 VAS points. BKP also led to an improvement of
      each radiographic outcome parameter immediately after surgery. Beck's ratio was
      improved from 0.71 to 0.83. The Cobb's angle of the relevant vertebral bodies
      decreased from 11.4 degrees  to 6.8 degrees . Monosegmental and bisegmental
      kyphosis angles decreased from 8.12 degrees  to 4.9 degrees  and from 6.9 degrees
      to 4.5 degrees  respectively. Within 1 year, however, there was a significant
      loss of correction in each radiographic parameter analyzed. Beck's ratio
      decreased to 0.72, Cobb's angle increased to 10.8 degrees , and the mono- and
      bisegmental kyphosis angles to 8.8 degrees  and 8.3 degrees , respectively.BKP
      does not result in a permanent realignment of the thoracolumbar spine following
      treatment of single level osteoporotic compression fractures.

PMID- 21960026
TI  - These are your rights.

PMID- 21960025
TI  - Intraorbital oculomotor nerve schwannoma affecting only the parasympathetic
      fibers.

PMID- 21960027
TI  - Biological reference values for chemical compounds in the work area (BARs): an
      approach for evaluating biomonitoring data.
AB  - Biological monitoring is a routine method that has been applied in occupational
      medical practice for many years. A requirement for its application is the
      availability of criteria suitable for evaluating biomonitoring data. Health-based
      threshold values are particularly useful as a criterion, yet only for substances
      for which effect thresholds can reliably be determined. For substances for which
      the concept of health-based threshold values is not applicable, the Working Group
      Setting of Threshold Limit Values in Biological Materials of the DFG Commission
      for the Investigation of Health Hazards of Chemical Compounds in the Work Area
      has recently established "Biologische Arbeitsstoff-Referenzwerte" (BARs,
      Biological Reference Values for Chemical Compounds in the Work Area) as an
      approach for evaluating biomonitoring data. The BAR represents the upper
      reference concentration of a biomarker in the general adult population without
      occupational exposure to the agent. It is derived from biomonitoring data of a
      sample of a defined population group. In general, a BAR corresponds to the 95th
      percentile of the sample distribution. Ideally, national environmental surveys
      including human biomonitoring results are used as basis for deriving BARs. The
      influence of age, sex, social status, residential area and life style factors on
      background exposure is considered in the evaluation of these values. Because
      tobacco smoking is the most frequent influencing factor, several BARs have been
      determined for non-smokers only. To date, BARs for 17 substances or substance
      groups are listed in the List of MAK and BAT Values 2011. BARs for another five
      substances have been discussed, but have not been established because of the
      insufficient scientific database. Establishing the BARs aims to facilitate the
      evaluation of human exposure to chemical compounds for which no health-based
      threshold values can be derived but an adequate assessment of exposure is
      required due to their toxicity. The application of BARs does not permit a
      toxicological evaluation, but does allow the occurrence and the extent of
      occupational exposure to hazardous substances to be proved.

PMID- 21960028
TI  - A time-stratified case-crossover study of fine particulate matter air pollution
      and mortality in Guangzhou, China.
AB  - OBJECTIVES: Few studies in China investigate health impact of fine particulate
      matter (PM(2.5)) due to lack of monitoring data and the findings are
      controversial. The aim of this study is to examine the short-association between
      PM(2.5) and daily mortality in Guangzhou, the economic center of south China.
      METHODS: In Guangzhou, we measured daily PM(2.5) concentrations between 2007 and
      2008 and conducted a time-stratified case-crossover analysis to explore the
      association between PM(2.5) and daily mortality, and examine potential effect
      modifiers including age, sex, and education. RESULTS: The averaged PM(2.5)
      concentration in 2007-2008 was 70.1 MUg/m(3) in Guangzhou, which was
      approximately seven times higher than the WHO Air Quality Guidelines for PM(2.5)
      (annual average: 10 MUg/m(3)). Regression analysis showed that ambient PM(2.5)
      was associated with mortality from all causes and cardiorespiratory diseases. An
      increase of 10 MUg/m(3) in 2-day moving average (lag01) concentration of PM(2.5)
      corresponds to 0.90% [95% confidence interval (CI): 0.55, 1.26%] increase of
      total mortality, 1.22% (95% CI: 0.63, 1.68%) increase of cardiovascular
      mortality, and 0.97% (95% CI: 0.16, 1.79%) increase of respiratory mortality. The
      associations were stronger in the elderly (aged 65 years or more), in females,
      and in those with low education level, but the differences were statistically
      insignificant. After adjustment for nitrogen dioxide (NO(2)), however, the
      effects of PM(2.5) decreased and became statistically insignificant. CONCLUSIONS:
      Our findings provided new information for the adverse health effects of PM(2.5)
      in China, and may have some implications for environmental policy making and
      standard setting in Guangzhou.

PMID- 21960029
TI  - Morphological and functional diversity of the mandible in suckermouth armored
      catfishes (Siluriformes: Loricariidae).
AB  - We examined the mandibles of 377 individuals representing 25 species, 12 genera,
      5 tribes, and 2 subfamilies of the Loricariidae, a species-rich radiation of
      detritivorous-herbivorous neotropical freshwater fishes distinguished by having a
      ventral oral disk and jaws specialized for surface attachment and benthic
      feeding. Loricariid mandibles are transversely oriented and bilaterally
      independent, each rotating predominantly around its long axis, although
      rotational axes likely vary with mandibular geometry. On each mandible, we
      measured three traditional and three novel morphological parameters chosen
      primarily for their functional relevance. Five parameters were linear distances
      and three of these were analogous to traditional teleost in- and out-levers for
      mandibular adduction. The sixth parameter was insertion area of the combined
      adductor mandibulae muscle (AM(area)), which correlated with adductor mandibulae
      volume across a subset of taxa and is interpreted as being proportional to
      maximum force deliverable to the mandible. Multivariate analysis revealed
      distributions of phylogenetically diagnosed taxonomic groupings in mandibular
      morphospace that are consistent with an evolutionary pattern of basal niche
      conservatism giving rise to multiple adaptive radiations within nested clades.
      Correspondence between mandibular geometry and function was explored using a 3D
      model of spatial relationships among measured parameters, potential forces, and
      axes of rotation. By combining the model with known loricariid jaw kinematics, we
      developed explicit hypotheses for how individual parameters might relate to each
      other during kinesis. We hypothesize that the ratio [AM(area) /tooth row
      length(2) ] predicts interspecific variation in the magnitude of force entering
      the mandible per unit of substrate contacted during feeding. Other newly proposed
      metrics are hypothesized to predict variation in aspects of mandibular mechanical
      advantage that may be specific to Loricariidae and perhaps shared with other
      herbivorous and detritivorous fishes.

PMID- 21960030
TI  - Correlation of arterial stiffness to left ventricular function in patients with
      reduced ejection fraction.
AB  - Heart failure has been divided into heart failure with preserved left ventricular
      (LV) ejection fraction (EF) and heart failure with reduced EF, because the
      pathophysiologies of the two conditions are different.  Cardio-ankle vascular
      index (CAVI) is a new indicator of arterial stiffness, and the most conspicuous
      feature of CAVI is its independence of blood pressure at the time of measurement.
      Arterial stiffness has been considered to increase LV afterload, which requires
      special care to avoid the onset of heart failure.  We compared the correlation of
      arterial stiffness as assessed by CAVI to LV function in 44 hypertensive patients
      with preserved EF (EF: 71 +/- 7%) and 31 patients with reduced EF (48 +/- 8%). 
      All of patients with reduced EF had history of both hypertension and myocardial
      infarction.  Using Doppler echocardiography, LV diastolic and systolic function
      was evaluated by measuring peak early diastolic mitral annular velocity (e') and
      global LV peak systolic longitudinal strain (GPSLS), respectively.  In patients
      with preserved EF, CAVI was correlated with e' (r = -0.313, p = 0.038), but not
      with GPSLS (r = 0.207).  By contrast, CAVI was correlated with GPSLS (r = 0.604,
      p < 0.001) as well as e' (r = -0.393, p = 0.029) in patients with reduced EF. 
      Thus, patients with reduced EF showed a closer correlation of arterial stiffness
      to LV function compared with patients with preserved EF.  Therefore, hypertensive
      patients with reduced EF require a stricter regimen for treating arterial
      stiffness than their counterparts with preserved EF.

PMID- 21960031
TI  - Mobile intervention design in diabetes: review and recommendations.
AB  - Mobile technology enhances the potential to assess, prompt, educate, and engage
      individuals with diabetes. The near-ubiquitous presence of mobile phones allows
      real-time contextually relevant support for diabetes self-care. We review the
      design of mobile interventions included in a recent meta-analysis. Although
      mobile programs can lead to improvements in glycemic control, many aspects, such
      as the role of the diabetes clinician, real-time features, and patient engagement
      have not been documented. Studies with the greatest impact on hemoglobin A(1c)
      integrated patient feedback and a role for clinicians. Research is needed
      regarding feasible and efficacious roles for clinical support in mobile
      interventions. Recommendations for design and research include the following:
      consideration of patient and clinician burden; identification of patterns and
      metrics for patient treatment adherence and engagement; integration of goal
      setting and problem solving; enhancing patient education; a greater focus on
      patient-centered motivational strategies; and utilization of study designs that
      relate intervention design elements to outcomes.

PMID- 21960032
TI  - Clinical comparison of two suspensory fixation devices for anatomic double-bundle
      anterior cruciate ligament reconstruction.
AB  - PURPOSE: The aim of this study was to compare the operation time required and the
      clinical outcome 2 years postoperatively, after anatomic double-bundle ACL
      reconstructions using hamstring tendon grafts fixed with either the EndoButton-CL
      BTB((r)) (ECL-BTB) or the EndoButton-CL((r)) (ECL). METHODS: Forty-six patients,
      who underwent anatomic double-bundle ACL reconstruction, were non-randomly
      divided into 2 groups. Patients with a combined ligament injury or complete
      meniscal tear were excluded from this study. In group I, an ECL was used with 23
      patients. In group II, an ECL-BTB was used with the remaining 23 patients. In
      groups I and II, the ECL or ECL-BTB was attached to the femoral ends of the
      hamstring tendon autografts. In both groups, a polyester tape was connected in
      series with the tibial ends of the grafts. The patients were examined with
      standard clinical evaluations at 2 years after surgery. RESULTS: The operation
      time in group II was significantly shorter than that in group I (P = 0.0459).
      Concerning the intra- and postoperative complications, there were no serious
      complications in either group. No significant differences were found between the
      2 groups in terms of knee laxity measurements, the peak muscle torque of
      quadriceps and hamstrings, the Lysholm score and the IKDC evaluation.
      CONCLUSIONS: This study demonstrated that the usage of the ECL-BTB for graft
      preparation significantly shortens the total operation time in comparison with
      the ECL and that there were no significant differences in the 2-year clinical
      outcome and the intra- and postoperative complications between the 2 graft
      preparation procedures of the anatomic double-bundle ACL reconstruction. The ECL
      BTB can be an alternative device for the hamstring tendon graft in double-bundle
      ACL reconstruction. LEVEL OF EVIDENCE: Prospective comparative cohort study,
      Level II.

PMID- 21960034
TI  - Phenotypic and genotypic properties of Neisseria gonorrhoeae isolates in Norway
      in 2009: antimicrobial resistance warrants an immediate change in national
      management guidelines.
AB  - Despite rapidly diminishing treatment options for Neisseria gonorrhoeae and high
      levels of ciprofloxacin resistance worldwide, Norwegian guidelines still
      recommend ciprofloxacin as empirical treatment for gonorrhea. The present study
      aimed to characterize phenotypical and genotypical properties of N. gonorrhoeae
      isolates in Norway in 2009. All viable N. gonorrhoeae isolates (n = 114) from six
      university hospitals in Norway (2009) were collected, representing 42% of all
      notified gonorrhea cases. Epidemiological data were collected from the Norwegian
      Surveillance System for Communicable Diseases and linked to phenotypical and
      genotypical characteristics for each N. gonorrhoeae isolate. Resistance levels to
      the antimicrobials examined were: ciprofloxacin 78%, azithromycin 11%, cefixime
      3.5%, ceftriaxone 1.8%, and spectinomycin 0%. The minimum inhibitory
      concentrations of gentamicin varied from 1.5 to 8 mg/L. Forty-one (36%) of the
      isolates were beta-lactamase-producing, 17 displayed penA mosaic alleles, and 72
      different N. gonorrhoeae multiantigen sequence types (ST; 37 novel) were
      identified. The most common ST was ST1407 (n = 11), containing penA mosaic
      allele. Four of these isolates displayed intermediate susceptibility/resistance
      to cefixime. The N. gonorrhoeae strains circulating in Norway were highly
      diverse. The level of ciprofloxacin resistance was high and the Norwegian
      management guidelines should promptly exclude ciprofloxacin as an empirical
      treatment option for gonorrhea.

PMID- 21960033
TI  - Cerebrospinal fluid diversion devices and infection. A comprehensive review.
AB  - Hydrocephalus is a common neurosurgical disease affecting approximately 40 per
      100,000 people. Cerebrospinal fluid diversion devices are essential in the
      management of this pathology. These devices include internal shunts and external
      ventricular drains. Infection is the most significant complication resulting from
      the high frequency of appearance and the consequences it involves, since it is
      associated with increased morbidity and mortality. It also involves increased
      hospital costs (approximately 40,000 euro per episode). In the present report the
      authors make a comprehensive review of cerebrospinal fluid diversion devices and
      their most important complication: infection. The authors make special emphasis
      on the epidemiology, aetiology, pathogenesis, risk factors, symptoms and signs,
      diagnosis, treatment and prevention of infection.

PMID- 21960035
TI  - Ethosomes(r) and transfersomes(r) containing linoleic acid: physicochemical and
      technological features of topical drug delivery carriers for the potential
      treatment of melasma disorders.
AB  - Two vesicular colloidal carriers, ethosomes(r) and transfersomes(r) were proposed
      for the topical delivery of linoleic acid, an active compound used in the
      therapeutic treatment of hyperpigmentation disorders, i.e. melasma, which is
      characterized by an increase of the melanin production in the epidermis. Dynamic
      light scattering was used for the physicochemical characterization of vesicles
      and mean size, size distribution and zeta potential were evaluated. The stability
      of formulations was also evaluated using the Turbiscan Lab(r) Expert based on the
      analysis of sample transmittance and photon backscattering. Ethosomes(r) and
      transfersomes(r) were prepared using Phospholipon 100 G(r), as the lecithin
      component, and ethanol and sodium cholate, as edge activator agents,
      respectively. Linoleic acid at 0.05% and 0.1% (w/v) was used as the active
      ingredient and entrapped in colloidal vesicles. Technological parameters, i.e.
      entrapment efficacy, drug release and permeation profiles, were also
      investigated. Experimental findings showed that physicochemical and technological
      features of ethosomes(r) and transfersomes(r) were influenced by the lipid
      composition of the carriers. The percutaneous permeation experiments of linoleic
      acid-loaded ethosomes(r) and transfersomes(r) through human stratum corneum
      epidermidis membranes showed that both carriers are accumulated in the skin
      membrane model as a function of their lipid compositions. The findings reported
      in this investigation showed that both vesicular carriers could represent a
      potential system for the topical treatment of hyperpigmentation disorders.

PMID- 21960036
TI  - An update on pathogenic mechanisms of inflammatory myopathies.
AB  - PURPOSE OF REVIEW: Our understanding of the pathogenesis of the inflammatory
      myopathies suggests an interplay between adaptive, innate immune, and nonimmune
      mechanisms in the damage and dysfunction that occur in myopathic muscle tissue.
      This review gives an update on the recent findings concerning some of these
      mechanisms and their relevance to disease diagnosis, prognosis, and therapy.
      RECENT FINDINGS: The presence of several additional immune cell types (CD-28 null
      T cells, regulatory T cells, plasmacytoid dendritic cells, plasma cells) and
      their roles in the various subsets of myositis are discussed. Likewise several
      new autoantibodies (e.g. 3-hydroxy-3 methylglutaryl-coenzyme-A reductase and
      melanoma differentiation-associated gene 5) and their association with disease
      phenotype are described. The review also discusses emerging evidence that
      cytokines (type 1 interferon) and Toll-like receptor signaling influence the
      local immune cell activation and response. The mechanisms involved in muscle
      degeneration are not clearly defined, but recent studies point to a role for
      nonimmune mechanisms such as endoplasmic reticulum stress and autophagy in
      skeletal muscle cell death and dysfunction in myositis. SUMMARY: The muscle
      microenvironment in inflammatory myopathy is complex. Multiple players such as
      adaptive and innate immune cells, cytokines, and chemokines as well as nonimmune
      mechanisms are involved. Understanding the nature of the relevant cell types and
      the molecular pathways underlying particular disease phenotypes should help to
      define therapeutic targets for myositis.

PMID- 21960037
TI  - Current world literature.

PMID- 21960039
TI  - The preferential accumulation of cadmium in the head portion of the freshwater
      planarian, Dugesia japonica (Platyhelminthes: Turbellaria).
AB  - Free-living freshwater planarians are considered to have the potential for
      development as an experimental model for toxicological studies on xenobiotics,
      including metals. However, little was known about the distribution patterns of
      metals in the body of treated planarians. This study was conducted to determine
      the tissue distribution patterns of cadmium (Cd) in different body portions of
      the treated planarian, Dugesia japonica. Results showed that Cd accumulated in
      the head of planarians at a significantly higher concentration than in the tail.
      After examining the level of metallothionein (MT), we suggested that the tissue
      distribution pattern of Cd might be related to MT induction patterns. In
      contrast, in planarians treated with copper (Cu), neither the tissue accumulation
      of Cu nor the multiples of induction of MTs significantly differed between
      different portions. Furthermore, a higher Cd accumulation rate in the head of
      planarians caused more-severe oxidative stress to appear in this portion and also
      a higher susceptibility to a lethal concentration of Cd. Finally, both in vitro
      and in vivo acetylcholinesterase activities in both body portions of planarians
      were inhibited by Cd. The present study provides the first report that different
      metals are distributed in various body portions with different patterns in the
      planarian.

PMID- 21960040
TI  - A decade of experience: Cryptococcus gattii in British Columbia.
AB  - It has been over a decade since Cryptococcus gattii was first recognized as the
      causative organism of an outbreak of cryptococcosis on Vancouver Island, British
      Columbia. A number of novel observations have been associated with the study of
      this emergent pathogen. A novel genotype of C. gattii, VGIIa was described as the
      major genotype associated with clinical disease. Minor genotypes, VGIIb and VGI,
      are also responsible for disease in British Columbians, in both human and animal
      populations. The clinical major genotype VGIIa and minor genotype VGIIb are
      identical to C. gattii isolated from the environment of Vancouver Island. There
      is more heterogeneity in VGI, and a clear association with the environment is not
      apparent. Between 1999 and 2010, there have been 281 cases of C. gattii
      cryptococcosis. Risk factors for infection are reported to be age greater than 50
      years, history of smoking, corticosteroid use, HIV infection, and history of
      cancer or chronic lung disease. The major C. gattii genotype VGIIa is as virulent
      in mice as the model Cryptococcus, H99 C. neoformans, although the outbreak
      strain produces a less protective inflammatory response in C57BL/6 mice. The
      minor genotype VGIIb is significantly less virulent in mouse models. Cryptococcus
      gattii is found associated with native trees and soil on Vancouver Island.
      Transiently positive isolations have been made from air and water. An ecological
      niche for this organism is associated within a limited biogeoclimatic zone
      characterized by daily average winter temperatures above freezing.

PMID- 21960041
TI  - Au/Pt and Au/Pt3Ni nanowires as self-supported electrocatalysts with high
      activity and durability for oxygen reduction.
AB  - Novel Au/Pt and Au/Pt(3)Ni nanostructures consisting of Pt and Pt(3)Ni alloy
      nanodendrites grown on Au nanowires were synthesized, which exhibited high
      electrocatalytic activity and durability toward oxygen reduction when used as
      self-supported catalysts.

PMID- 21960042
TI  - A new modification of an old framework: Hofmann layers with unusual
      tetracyanidometallate groups.
AB  - Cyanidometallate complexes are highly versatile building units for the generation
      of functional porous materials. Here we report five new pillared Hofmann layer
      compounds incorporating the tetracyanidometallates [MoO(CN)(4)](2-) and
      [MnN(CN)(4)](2-). These metalloligands, which are new to this class of materials,
      have been combined with divalent 1st-row transition metals to produce Hofmann
      layers that are linked into three-dimensional frameworks by ditopic bridging
      dipyridyls. We report the structures and anomalous thermal expansion properties
      of five new materials: [Mn(H(2)O)(bpy)(1/2){MoO(CN)(4)(bpy)(1/2)}].2H(2)O (1),
      [Mn(H(2)O)(bpy)(1/2){MnN(CN)(4)(bpy)(1/2)}].2H(2)O (2),
      [Fe(H(2)O)(bpy)(1/2){MnN(CN)(4)(bpy)(1/2)}].2H(2)O (3),
      [Co(H(2)O)(bpy)(1/2){MnN(CN)(4)(bpy)(1/2)}].2H(2)O (4) and
      [{Mn(H(2)O)(2)}(1/2){Mn(bpa)(2)}(1/2){MoO(CN)(4)(bpa)(1/2)}].MeOH (5), (where bpy
      = 4,4'-bipyridine and bpa = 4,4'-bipyridylacetylene).

PMID- 21960043
TI  - Complete genome sequence of a dahlia common mosaic virus isolate from New
      Zealand.
AB  - Dahlia mosaic disease of the ornamental flowering plant Dahlia is caused by two
      caulimoviruses, dahlia mosaic virus (DMV) and dahlia common mosaic virus (DCMV).
      We used a rolling-circle amplification method to amplify, clone and determine for
      the first time the full genome sequence of a DCMV isolate from New Zealand (DCMV
      NZ). Within the 7949-bp circular double-stranded retro-transcribing DCMV-NZ DNA,
      we identified six putative open reading frames, typical of all genomes in the
      family Caulimoviridae. The availability of the complete DCMV sequence provides a
      reference genome against which all others can be compared.

PMID- 21960044
TI  - Comparison of embryonic expression within multigene families using the FlyExpress
      discovery platform reveals more spatial than temporal divergence.
AB  - BACKGROUND: Overlaps in spatial patterns of gene expression are frequently an
      initial clue to genetic interactions during embryonic development. However,
      manual inspection of images requires considerable time and resources impeding the
      discovery of important interactions because tens of thousands of images exist.
      The FlyExpress discovery platform was developed to facilitate data-driven
      comparative analysis of expression pattern images from Drosophila embryos.
      RESULTS: An image-based search of the BDGP and Fly-FISH datasets conducted in
      FlyExpress yields fewer but more precise results than text-based searching when
      the specific goal is to find genes with overlapping expression patterns. We also
      provide an example of a FlyExpress contribution to scientific discovery: an
      analysis of gene expression patterns for multigene family members revealed that
      spatial divergence is far more frequent than temporal divergence, especially
      after the maternal to zygotic transition. This discovery provides a new clue to
      molecular mechanisms whereby duplicated genes acquire novel functions.
      CONCLUSIONS: The application of FlyExpress to understanding the process by which
      new genes acquire novel functions is just one of a myriad of ways in which it can
      contribute to our understanding of developmental and evolutionary biology. This
      resource has many other potential applications, limited only by the
      investigator's imagination.

PMID- 21960045
TI  - Effects of testosterone, estrogen and progesterone on TNF-alpha mediated cellular
      damage in rat arthritic synovial fibroblasts.
AB  - Sexual dimorphism is a well-established phenomenon in rheumatoid arthritis, with
      women exhibiting higher disease severity. Understanding the role of sex hormones
      using in vivo animal models is limited due to the systemic effects as well as the
      difficulty in exploring different dose combinations of the hormones
      simultaneously. However, cell culture systems pose ideal systems for exploring
      different combinations and concentrations of the hormones simultaneously. In this
      study, the procedure for isolation of arthritic fibroblasts was standardized
      using a combination of collagenase and trypsin based on maximal yield and
      viability after employing different enzymatic disaggregation procedures. The
      cultured synovial fibroblasts from arthritic rats did not differ significantly
      from normal rat fibroblasts in terms of proliferation or secretion of
      inflammatory mediators. Stimulation of fibroblasts with TNF-alpha was
      standardized and TNF-alpha stimulated rat arthritic synovial fibroblasts
      exhibited an ideal in vitro system for screening antiinflammatory molecules. The
      effects of physiological and pharmacological concentrations of testosterone,
      estrogen and progesterone were studied on TNF-alpha induced cellular damage in
      rat arthritic synovial fibroblasts. The results showed that estrogen and
      testosterone exerted antiinflammatory effects on rat arthritic synovial
      fibroblasts at physiological and pharmacological concentrations. However, there
      was no significant difference in the effects between physiological and
      pharmacological concentrations. Progesterone independently did not show any
      protective effects. In combination with physiological concentrations of estrogen,
      progesterone abrogated estrogen's protective effect but it exhibited protection
      in combination with pharmacological concentrations of estrogen.

PMID- 21960046
TI  - Diagnostic value of anti-cyclic citrullinated peptide antibody for rheumatoid
      arthritis in a Chinese population: a meta-analysis.
AB  - To use meta-analysis to determine the accuracy of anti-cyclic citrullinated
      peptide (CCP) antibody in diagnosis of patients with rheumatoid arthritis (RA) in
      a Chinese population, we searched MEDLINE and CNKI databases for studies
      published in English or Chinese between January 2000 and June 2010. Two
      investigators independently evaluated studies for inclusion, data extraction, and
      quality assessment. We used a random-effects model to combine estimates of
      sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood
      ratio (LR-), and diagnostic odds ratio (DOR). One hundred and eighteen studies
      met our inclusion criteria. All studies were of high quality. The summary
      estimates for anti-CCP antibody in the diagnosis of RA in a Chinese population
      were as follows: sensitivity 0.65 (95% confidence interval (CI) 0.65-0.66),
      specificity 0.95 (95% CI 0.95-0.96), positive likelihood ratio (LR+) 15.84 (95%
      CI 13.55-18.54), negative likelihood ratio (LR-) 0.33 (95% CI 0.31-0.35), and
      diagnostic odds ratio (DOR) 51.60 (95% CI 43.64-61.01). With high specificity and
      moderate sensitivity, anti-CCP antibody tests play an important role in
      conforming the diagnosis of RA in a Chinese population.

PMID- 21960047
TI  - Evaluation of skin thickness lesions in patients with Lyme disease measured by
      modified Rodnan total skin score.
AB  - Recently, a possible etiological connection between infection with Borrelia
      burgdorferi and various skin lesions, including morphea and systemic sclerosis
      (SSc), has been discussed. The aim of our study was the evaluation of frequency
      of skin thickening typical of SSc or morphea in the group of patients with Lyme
      disease (LD) with frequent exposition to tick bites. The group consisted of 110
      patients with LD frequently exposed to tick bites form the northeastern Poland,
      which is an endemic area for this disease. To measure the skin lesions, the
      modified Rodnan total skin score (RTSS) was used. In the analyzed group, no skin
      changes typical of morphea or skin thickening were found. According to RTSS, all
      patients scored 0 points. Raynaud's phenomenon in all patients was not found. The
      relationship between scleroderma or morphea and LD is still a matter of
      controversy. Described by some authors, cases with LD and scleroderma may be
      associated with co-existence of B. burgdorferi infection with autoimmune process.

PMID- 21960048
TI  - Balneotherapy for chronic low back pain: a randomized, controlled study.
AB  - A large number of treatments were used for patients with chronic low back pain.
      Frequent episodes have been reported very high. Although balneotherapy was found
      effective in this disease, there are not well-designed studies. We aimed to
      determine the effectiveness of balneotherapy versus physical therapy in patients
      with chronic low back pain. Exercise was added to both treatment programs. Sixty
      patients with chronic low back pain were randomly divided into two groups.
      Physical modalities plus exercise were applied to group 1, and group 2 was
      received balneotherapy plus exercise for ten sessions. The following parameters
      were measured: visual analogue scale at rest and movement for pain, paracetamol
      dose, manual muscle test for lumber muscles, modified Schoeber' test, Oswestry
      disability index, and Short-Form 36 at the beginning and end of the therapies and
      at the 3 months follow-up. The statistical analyses were performed using the SPSS
      10.0 program. Both groups achieved significant improvements within themselves.
      But balneotherapy groups were improved at back extensor muscle test (P < 0.05),
      modified Schoeber's test (P < 0.03), Oswestry disability index, and the some
      scores of SF 36 (energy vitality, social function, role limitations related to
      physical problems, and general health P < 0.05). Balneotherapy combined with
      exercise therapy had advantages than therapy with physical modalities plus
      exercise in improving quality of life and flexibility of patients with chronic
      low back pain.

PMID- 21960050
TI  - The near demise and subsequent revival of classical genetics for investigating
      Caenorhabditis elegans embryogenesis: RNAi meets next-generation DNA sequencing.
AB  - Molecular genetic investigation of the early Caenorhabditis elegans embryo has
      contributed substantially to the discovery and general understanding of the
      genes, pathways, and mechanisms that regulate and execute developmental and cell
      biological processes. Initially, worm geneticists relied exclusively on a
      classical genetics approach, isolating mutants with interesting phenotypes after
      mutagenesis and then determining the identity of the affected genes.
      Subsequently, the discovery of RNA interference (RNAi) led to a much greater
      reliance on a reverse genetics approach: reducing the function of known genes
      with RNAi and then observing the phenotypic consequences. Now the advent of next
      generation DNA sequencing technologies and the ensuing ease and affordability of
      whole-genome sequencing are reviving the use of classical genetics to investigate
      early C. elegans embryogenesis.

PMID- 21960051
TI  - Analysis of the corrective forces exerted by a dynamic derotation brace (DDB).
AB  - BACKGROUND: Discrepancies exist in the current literature for bracing of spinal
      curvature conditions. This can be explained by the diversity of brace types, the
      different curve patterns and the various measurement methods and instruments.
      OBJECTIVES: The aim of this study was the analysis of the corrective forces
      exerted by a dynamic derotation brace (DDB), at the skin-brace interface,
      altering the strap tension and body posture. STUDY DESIGN: We analysed the direct
      forces exerted by a DDB's main pad, on 44 (38 girls, 6 boys) idiopathic scoliotic
      patients. Twenty-seven patients had a single right thoracic and 17 a single left
      or right thoracolumbar curve. METHODS: We used the F-Socket 9801 pressure sensor
      and the MatScan Research BETA STAM 6.30 software, while patients adopted nine
      different postures. The patients were divided into three different groups: those
      who wore the brace for the first time, those who were changing their brace for a
      new one, and those who were having adjustments made to their existing brace.
      RESULTS: These patients who were having adjustments made to their existing brace
      caused the highest mean exerted force. Changes in strap tension and body posture
      resulted in statistically significant alterations of the interface pressure and
      the forces exerted on the patient's body. CONCLUSIONS: Tightening the brace's
      straps always produces a significant force increase, independent of the body
      posture and the curve type. Also there are some body postures which significantly
      modify the exerted force. The body posture of maximum inspiration for
      thoracolumbar curves and, additionally, prone and lying left for thoracic curves.

PMID- 21960052
TI  - Perceptions of cosmesis and function in adults with upper limb prostheses: a
      systematic literature review.
AB  - BACKGROUND: Technological developments in prosthesis design of upper limb devices
      are improving rapidly, and understandings of user's perceptions are important to
      reduce device abandonment and improve user satisfaction rates. OBJECTIVES: The
      purpose of this review was to establish what is known about adult user's
      perceptions of upper limb prostheses in terms of both cosmesis and function.
      STUDY DESIGN: Systematic review. METHODS: A search of the literature between 1990
      and 2010 identified over 600 possible citations; these were reduced to 15
      citations based on selection criteria. RESULTS: The main themes arising from the
      review were user satisfaction ratings with current prostheses, priorities for
      future design and the social implications of wearing a prosthetic limb. While
      users of cosmetic prostheses were mostly satisfied with their prostheses,
      satisfaction rates vary considerably across studies, due to variability in
      demographics of users and an ambiguity over the definitions of cosmesis and
      function. Design priorities also varied, though overall there is a slight trend
      toward prioritising function over cosmesis. The qualitative studies noted the
      importance users placed on presenting a 'normal' appearance and 'not standing
      out'. CONCLUSIONS: The reviewed studies mostly examine functionality and cosmesis
      as separate constructs, and conclusions are limited due to the disparity of user
      groups studied. Recommendations are made for further work to explore
      understandings of these constructs in relation to upper limb prosthesis use.

PMID- 21960055
TI  - Novel thermo-responsive coloring phenomena in water/surfactant/oil emulsions.
AB  - Emulsions comprising a dual-surfactant system of a long-chain amidoamine
      derivative and a quaternary ammonium salt developed an iridescent color at a
      specific temperature region. The emulsions underwent phase inversion on heating
      from an O/W emulsion to a W/O emulsion, passing through a periodical lamellar
      structure which developed a characteristic interference color. Interestingly, the
      color and the coloring temperature can be independently controlled by adjusting
      the concentration of surfactants, respectively.

PMID- 21960053
TI  - Pattern recognition control of multifunction myoelectric prostheses by patients
      with congenital transradial limb defects: a preliminary study.
AB  - BACKGROUND: Electromyography (EMG) pattern recognition offers the potential for
      improved control of multifunction myoelectric prostheses. However, it is unclear
      whether this technology can be successfully used by congenital amputees.
      OBJECTIVE: The purpose of this investigation was to assess the ability of
      congenital transradial amputees to control a virtual multifunction prosthesis
      using EMG pattern recognition and compare their performance to that of acquired
      amputees from a previous study. STUDY DESIGN: Preliminary cross-sectional study.
      METHODS: Four congenital transradial amputees trained and tested a linear
      discriminant analysis (LDA) classifier with four wrist movements, five hand
      movements, and a no-movement class. Subjects then tested the classifier in real
      time using a virtual arm. RESULTS: Performance metrics for the residual limb were
      poorer than those with the intact limb (classification accuracy: 52.1% +/- 15.0%
      vs. 93.2% +/- 15.8%; motion-completion rate: 49.0%+/- 23.0% vs. 84.0% +/- 9.4%;
      motion-completion time: 2.05 +/- 0.75 s vs. 1.13 +/- 0.05 s, respectively). On
      average, performance with the residual limb by congenital amputees was reduced
      compared to that reported for acquired transradial amputees. However, one subject
      performed similarly to acquired amputees. CONCLUSIONS: Pattern recognition
      control may be a viable option for some congenital amputees. Further study is
      warranted to determine success factors.

PMID- 21960056
TI  - 95Mo nuclear magnetic resonance parameters of molybdenum hexacarbonyl from
      density functional theory: appraisal of computational and geometrical parameters.
AB  - Solid-state (95)Mo nuclear magnetic resonance (NMR) properties of molybdenum
      hexacarbonyl have been computed using density functional theory (DFT) based
      methods. Both quadrupolar coupling and chemical shift parameters were evaluated
      and compared with parameters of high precision determined using single-crystal
      (95)Mo NMR experiments. Within a molecular approach, the effects of major
      computational parameters, i.e. basis set, exchange-correlation functional,
      treatment of relativity, have been evaluated. Except for the isotropic parameter
      of both chemical shift and chemical shielding, computed NMR parameters are more
      sensitive to geometrical variations than computational details. Relativistic
      effects do not play a crucial part in the calculations of such parameters for the
      4d transition metal, in particular isotropic chemical shift. Periodic DFT
      calculations were tackled to measure the influence of neighbouring molecules on
      the crystal structure. These effects have to be taken into account to compute
      accurate solid-state (95)Mo NMR parameters even for such an inorganic molecular
      compound.

PMID- 21960057
TI  - Allogeneic hematopoietic stem cell transplantation for ATL with central nervous
      system involvement: the Nagasaki transplant group experience.
AB  - Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is regarded as a
      curative option for aggressive adult T cell leukemia-lymphoma (ATL). However, the
      efficacy and safety of allo-HSCT for ATL with central nervous system (CNS)
      involvement, which is highly resistant to chemotherapy, remain controversial. We
      analyzed 10 ATL patients with CNS involvement who received allo-HSCT at three
      institutions in Nagasaki prefecture between 2000 and 2007. The 3-year overall
      survival rate was 40%, and the median observation time of the four surviving
      patients was 1532 days (range 945-2212 days). Two of four surviving patients
      received highly intensive local treatment for the CNS; one with 26 intrathecal
      injections of antineoplastic agents, and the other with whole cerebrospinal
      irradiation before transplantation. However, the other two patients received
      conventional or reduced-intensity conditioning with standard intrathecal
      chemotherapy. Three of the four surviving patients experienced chronic GVHD, and
      two of three patients with grade 3 or 4 acute GVHD were free from CNS relapse.
      From these data, it seems that both intensive local treatment for CNS disease and
      systemic GVHD contributed to the long-term control of CNS involvement. Although
      our data suggest that allo-HSCT is a therapeutic option for ATL with CNS disease,
      high transplant-related mortality (six cases) indicates the need for further
      studies to develop more effective procedures for CNS disease, and to reduce
      transplant-related morbidity.

PMID- 21960058
TI  - Type 2B-like acquired von Willebrand syndrome.

PMID- 21960060
TI  - Measuring local context as context-word probabilities.
AB  - Context enables readers to quickly recognize a related word but disturbs
      recognition of unrelated words. The relatedness of a final word to a sentence
      context has been estimated as the probability (cloze probability) that a
      participant will complete a sentence with a word. In four studies, I show that it
      is possible to estimate local context-word relatedness based on common language
      usage. Conditional probabilities were calculated for sentences with published
      cloze probabilities. Four-word contexts produced conditional probabilities
      significantly correlated with cloze probabilities, but usage statistics were
      unavailable for some sentence contexts. The present studies demonstrate that a
      composite context measure based on conditional probabilities for one- to four
      word contexts and the presence of a final period represents all of the sentences
      and maintains significant correlations (.25, .52, .53) with cloze probabilities.
      Finally, the article provides evidence for the effectiveness of this measure by
      showing that local context varies in ways that are similar to the N400 effect and
      that are consistent with a role for local context in reading. The Supplemental
      materials include local context measures for three cloze probability data sets.

PMID- 21960059
TI  - miR-34a predicts survival of Ewing's sarcoma patients and directly influences
      cell chemo-sensitivity and malignancy.
AB  - Identification of factors to detect chemotherapy-resistant tumours at diagnosis
      is a first priority for risk-adapted therapy in the oncology of children and
      young adults, where more individualized, effective, and less toxic treatments are
      highly desirable. In this study, we analysed the miRNAs discriminating Ewing's
      sarcoma (EWS) patients with different clinical outcomes in order to identify new
      indicators of prognosis. miRNA expression was investigated in 49 primary EWSs by
      using the Agilent human miRNA microarray v.2 and/or qRT-PCR. Statistical power of
      the samples studied for miRNA expression was verified, indicating adequate sample
      size. Microarray analysis defined a signature of five miRNAs (miR-34a, miR-23a,
      miR-92a, miR-490-3p, and miR-130b) as an independent predictor of risk for
      disease progression and survival. Validation analysis in the extended sample set
      indicated that both miR-34a and miR-490-3p achieved sufficient statistical power
      to predict prognosis. Results were particularly robust for miR-34a, which
      appeared associated with either event-free or overall survival and emerged as a
      significant predictor also after multivariate analysis. Patients with the highest
      expression of miR-34a did not experience adverse events in 5 years; in contrast,
      patients with the lowest expression recurred within 2 years. High expression of
      miR34a can be detected also in paraffin-embedded tissues by in situ
      hybridization, thus contributing to an easy routine evaluation of this miRNA.
      Functional analysis of miR-34a in EWS cell lines indicated that when miR-34a
      expression was enforced, cells were less proliferative, less malignant, and
      sensitized to doxorubicin and vincristine. Expression of miR-34a could be
      increased in p53wt cells by treatment with nutlin-3a. Accordingly, nutlin-3a
      synergizes with doxorubicin. Overall, our data indicate that miR-34a expression
      is a strong predictor of outcome in EWS. Restoration of miR-34a activity may be
      useful to decrease malignancy and increase tumour sensitivity to current drugs,
      so sparing excessive long-term toxicity to EWS patients.

PMID- 21960061
TI  - Use of the estimated intraclass correlation for correcting differences in effect
      size by level.
AB  - In a meta-analysis of intervention or group comparison studies, researchers often
      encounter the circumstance in which the standardized mean differences (d-effect
      sizes) are computed at multiple levels (e.g., individual vs. cluster). Cluster
      level d-effect sizes may be inflated and, thus, may need to be corrected using
      the intraclass correlation (ICC) before being combined with individual-level d
      effect sizes. The ICC value, however, is seldom reported in primary studies and,
      thus, may need to be computed from other sources. This article proposes a method
      for estimating the ICC value from the reported standard deviations within a
      particular meta-analysis (i.e., estimated ICC) when an appropriate default ICC
      value (Hedges, 2009b) is unavailable. A series of simulations provided evidence
      that the proposed method yields an accurate and precise estimated ICC value,
      which can then be used for correct estimation of a d-effect size. The effects of
      other pertinent factors (e.g., number of studies) were also examined, followed by
      discussion of related limitations and future research in this area.

PMID- 21960062
TI  - Defects in rutile and anatase polymorphs of TiO2: kinetics and thermodynamics
      near grain boundaries.
AB  - The direct consequence of irradiation on a material is the creation of point
      defects-typically interstitials and vacancies, and their aggregates-but it is the
      ultimate fate of these defects that determines the material's radiation
      tolerance. Thus, understanding how defects migrate and interact with sinks, such
      as grain boundaries, is crucial for predicting the evolution of the material. We
      examine defect properties in two polymorphs of TiO(2)-rutile and anatase-to
      determine how these materials might respond differently to irradiation. Using
      molecular statics and temperature accelerated dynamics, we focus on two issues:
      how point defects interact with a representative grain boundary and how they
      migrate in the bulk phase. We find that grain boundaries in both polymorphs are
      strong sinks for all point defects, though somewhat stronger in rutile than
      anatase. Further, the defect kinetics are very different in the two polymorphs,
      with interstitial species diffusing quickly in rutile while oxygen defects-both
      interstitials and vacancies-are fast diffusers in anatase. These results allow us
      to speculate on how grain boundaries will modify the radiation tolerance of these
      materials. In particular, grain boundaries in rutile will lead to a space charge
      layer at the boundary and a vacancy-rich damage structure, while in anatase the
      damage structure would likely be more stoichiometric, but with larger defects
      consisting primarily of Ti ions.

PMID- 21960064
TI  - Preventing cardioembolic stroke in atrial fibrillation with dabigatran.
AB  - Dabigatran is a direct inhibitor of thrombin that has recently been approved for
      primary and secondary stroke prevention and prevention of systemic embolism in
      patients with atrial fibrillation. The RE-LY (Randomized Evaluation of Long Term
      Anticoagulant Therapy [with Dabigatran Etexilate]) study showed that dabigatran
      given at a dose of 110 mg twice a day (bid) was associated with rates of stroke
      and systemic embolism that were similar to those associated with warfarin
      (International Normalized Ratio target 2.0-3.0), and lower rates of major
      hemorrhage. Dabigatran administered at a dose of 150 mg bid was significantly
      more effective compared with warfarin and showed a similar rate of major
      hemorrhages. Both dosages resulted in an approximately 60% to 70% relative
      reduction of intracranial hemorrhage. The dosage of 110 mg bid should be
      preferably used in patients older than 75 years at a higher bleeding risk. The
      Hemoclot (Hyphen BioMed, Mason, OH) test to measure dabigatran serum
      concentration is commercially available, but presence of the drug may also be
      detected using the activated partial thromboplastin time or thrombin time.

PMID- 21960063
TI  - Intensity of aphasia therapy: evidence and efficacy.
AB  - Determining the optimal amount and intensity of treatment is essential to the
      design and implementation of any treatment program for aphasia. A growing body of
      evidence, both behavioral and biological, suggests that intensive therapy
      positively impacts outcomes. We update a systematic review of treatment studies
      that directly compares conditions of higher and lower intensity treatment for
      aphasia. We identify five studies published since 2006, review them for
      methodologic quality, and synthesize their findings with previous ones. For both
      acute and chronic aphasia, results at the language impairment and communication
      activity/participation levels tend to be more equivocal than previously
      demonstrated, with no clear differences between intensive and nonintensive
      treatment emerging across studies. Future research directions are discussed
      including research design, definitions of treatment intensity, and behavioral and
      biological measurement of short- and long-term changes following implementation
      of an intensive treatment.

PMID- 21960066
TI  - A mutation in the Norrie disease gene (NDP) associated with familial exudative
      vitreoretinopathy.

PMID- 21960065
TI  - Axial protocadherin (AXPC) regulates cell fate during notochordal morphogenesis.
AB  - The separation and specification of mesoderm into the notochord and somites
      involves members of the non-clustered delta-protocadherins. Axial (AXPC) and
      paraxial (PAPC) protocadherins are expressed in the early dorsal mesoderm and
      later become refined to the developing notochordal and somitic mesoderm,
      respectively. The role of PAPC in this process has been studied extensively, but
      the role of AXPC is poorly understood. Partial knockdown of AXPC causes a
      specific bent-axis phenotype, while more severe knockdown results in the loss of
      notochord formation. The inability of these embryos to develop a notochord is not
      due to a cell-sorting event via changes in cell adhesion during gastrulation, but
      rather this defect is manifested through the loss of axial mesoderm
      specification, but not general mesoderm induction. The results presented here
      show that AXPC functions in notochord morphogenesis by directing cell-fate
      decisions rather than cell-cell adhesion.

PMID- 21960067
TI  - Current concepts and future directions in the pathogenesis and treatment of non
      infectious intraocular inflammation.
AB  - The blockbuster drug paradigm is under increasing scrutiny across the
      biopharmaceutical industry. Intraocular inflammation poses particular challenges
      to this, given the heterogeneity of conditions in the uveitis spectrum, and the
      increasing acknowledgement of individual patient and disease variance in
      underlying immune responses. This need has triggered a drive towards personalised
      and stratified medicine, supported and enabled as a result of continued
      development of both experimental models and molecular biological techniques and
      improved clinical classification. As such we have the ability now to
      systematically appraise at a genomic, transcriptomic, and proteomic level
      individual immunophenotype, and the promise that in the eye this can be augmented
      by in vivo immune imaging to identify individual immunopathology. With such
      advances all running in parallel, we are entering an era of experimental medicine
      that will facilitate early diagnosis, generate biomarkers for accurate
      prognostication, and enable the development of individualised and targeted
      therapies, which can progress rapidly into clinical practice.

PMID- 21960069
TI  - Knockdown of stomatin-like protein 2 (STOML2) reduces the invasive ability of
      glioma cells through inhibition of the NF-kappaB/MMP-9 pathway.
AB  - Stomatin-like protein 2 (STOML2), a member of the stomatin family, has been
      reported to be up-regulated in several types of human cancers. The clinical
      significance and biological role of STOML2 in gliomas remain largely unknown.
      Here, we describe the significantly up-regulated expression of STOML2 in glioma
      cell lines and glioma tissues at both the transcriptional and translational
      levels. Silencing endogenous STOML2 in glioma cells and primary glioma cells
      drastically reduced their migratory speed and invasive ability, associated with
      induction of matrix metallopeptidase 9 (MMP-9). We also demonstrated that
      knockdown of STOML2 significantly inhibited the transcriptional activity of NF
      kappaB and repressed the expression levels of NF-kappaB target genes, including
      MMP-9. A luciferase reporter assay revealed that the impact of STOML2 on MMP-9
      expression is NF-kappaB-dependent. Immunohistochemical analysis showed that the
      up-regulation of STOML2 was significantly correlated with the WHO histological
      grade of gliomas (p < 0.001). Patients with higher STOML2 expression levels had
      an overall shorter survival time, whereas patients with lower expression of
      STOML2 had a longer survival time. A multivariate analysis revealed that STOML2
      expression might be an independent prognostic indicator for the survival of
      glioma patients. Taken together, our results suggest that overexpression of
      STOML2 is associated with glioma aggressiveness and may represent an independent
      prognostic factor for the outcome of glioma patients.

PMID- 21960070
TI  - Using biochemical findings to study the effect of silymarin on the liver of
      pregnant rat that consumed ethanol.
AB  - In pregnancy period, there is high risk of hepatic diseases and alcohol
      consumption increases such risk. Some pregnant mothers are not able to quit the
      habit of drinking alcohol or they are unaware of its dangers. Finding a drug
      which is effective and efficient in reducing ethanol misuse consequences during
      pregnancy can assist the decrease of harmful effects of this habit. The purpose
      of the current research is to investigate the effects of oral administration of
      silymarin in preventing consequences of ethanol consumption on the liver during
      pregnancy, using the rat animal model as well as biochemical findings and
      clinical symptoms. 45 female rats were randomly divided into 3 groups, each
      composed of 15 rats. After the first day of pregnancy, the study was performed as
      follows. The first group received distilled water. The second group was given
      ethanol equivalent to 35% of their total required calorie. Furthermore, the third
      group received the same amount of ethanol plus 200 mg/kg silymarin. In order to
      evaluate liver's activity, biochemical analysis was performed at days 1, 7, 14,
      and 21, to measure the amount of the enzymes ALT, AST, ALP, and bilirubin. The
      nutrition and clinical status of animal in the groups was studied and recorded 2
      times daily. This study showed that silymarin's protective effects are expressed
      from the first day of treatment.

PMID- 21960068
TI  - Twenty-four hour efficacy with the dorzolamide/timolol-fixed combination compared
      with the brimonidine/timolol-fixed combination in primary open-angle glaucoma.
AB  - AIM: The aim of this study is to compare the 24-hour efficacy of
      dorzolamide/timolol-fixed combination (DTFC) and brimonidine/timolol-fixed
      combination (BTFC) in primary open-angle glaucoma (POAG). METHODS: One eye each
      of 77 POAG patients was included in this prospective, observer-masked, crossover
      comparison. Following a 2-month timolol run-in period, patients had three
      intraocular pressure (IOP) measurements at 1000, 1200 and 1400 h while on timolol
      treatment. Patients showing at least a 20% IOP reduction on timolol were
      randomised to 3 months of therapy with DTFC or BTFC, and then were crossed over
      to the opposite therapy. RESULTS: Sixty POAG patients completed the study. The
      mean 24-hour IOP was significantly reduced with both the fixed combinations
      compared with the timolol-treated diurnal IOP (P < 0.001). When the two fixed
      combinations were compared directly, DTFC demonstrated a lower mean 24-hour IOP
      level as compared with BTFC (mean difference: -0.7 mm Hg, 95% confidence interval
      (CI): (-1.0, -0.3), P < 0.001). At two individual time points, DTFC significantly
      reduced IOP more than BTFC: at 1800 h (-1.0 mm Hg, 95% CI (-1.6,-0.5), P = 0.001)
      and at 0200 (-0.9 mm Hg, 95% CI: (-1.4,-0.5), P = 0.001). No significant
      difference existed for the other time points. CONCLUSION: Both the fixed
      combinations significantly reduce 24-hour IOP in POAG. DTFC provided
      significantly better 24-hour efficacy.

PMID- 21960071
TI  - Clinical outcome and cost in patients with off-pump vs. on-pump coronary artery
      bypass surgery.
AB  - General concept and major emphasis on off-pump coronary artery bypass surgery
      (OPCAB) is maintaining quality of care and patient safety while reducing cost and
      resource utilization. OPCAB probably avoids the potential complications of
      cardiopulmonary bypass. However its acceptance depends on clinical and economic
      outcome. The aim of this study is to compare clinical and economic outcome of off
      pump and on pump coronary artery bypass surgery. This is a report of an analytic
      cross-sectional study on 304 patients underwent coronary artery bypass surgery
      that were randomized into conventional on pump and off-pump groups. Variables and
      costs were obtained for each group and these data were analyzed using parametric
      methods. There was no difference between the two groups with respect to
      perioperative and intraoperative patient's variables. OPCAB reduced the need for
      postoperative transfusion requirement (P<0.05) which was statistically
      significant and showed a trend towards reduction of morbidity although didn't
      reach statistical significance (P>0.05). There were no statistically significant
      differences in surgical re exploration and length of stay between the two groups.
      The mean cost for an on pump surgery was 8312000 +/- 2859 Rials per patient that
      was significantly higher than an off-pump surgery. Based on the findings of this
      study, clinical outcome has no statistically significant difference between on
      pump and off-pump CABG but the costs are significantly higher in the on pump
      group.

PMID- 21960072
TI  - Timing of surgery for aneurysmal subarachnoid hemorrhage.
AB  - Despite the many studies about timing for surgery in subarachnoid hemorrhage
      (SAH), the optimum time is still unclear. The aim of this study was to determine
      the results of early and late surgery for aneurysmal subarachnoid hemorrhage. In
      this cross-sectional study we evaluated the results of 70 consecutive surgery for
      aneurysmal subarachnoid hemorrhage in in Firuzgar hospital from 2005 to 2008.
      Surgery was performed in 50 cases (71.4%) in early period after SAH (first 4
      days) and in 20 cases (28.6%) in at least 7 days after SAH. Statitical analysis
      was done by SPSS software, using Chi-square and t-test. Mean age of patients was
      48.54 +/- 13.4 years. 41.4% of patients were male and 58.6% were female. Most
      (77.2%) of patients had clinical grade I or II. 92.9% of aneurysms were single.
      Hypertension was the most common associated disease (34.3%). The most common site
      of aneurysms was anterior communicating artery (41.4%), followed by middle
      cerebral artery (35.7%). The outcome of surgery was favorable in 70% and
      unfavorable in 30%. Mortality rate was 24.3%. Outcome was favorable in 66% of
      early surgeries and 80% of late surgeries. There was no statistically significant
      difference between early and late surgery in terms of complications and outcome.
      Mean hospital stay of patients in the early surgery group was significantly lower
      than late group (16.46 +/- 9.36 vs. 22.5 +/- 7.97 days; P=0.01). The results of
      early and late surgery for aneurysmal subarachnoid hemorrhage is similar and
      decision making for timing of surgery should be based on each patient individual
      clinical conditions, age, size and site of aneurysm.

PMID- 21960073
TI  - Comparison of the effects of anesthesia with isoflurane and total intravenous
      anesthesia on the intensity of body temperature reduction during anesthesia and
      incidence of postoperative chills.
AB  - This study compared the effects of anesthesia with isoflurane and TIVA (total
      intravenous anesthesia) on the intensity of body temperature reduction during
      anesthesia and incidence of chills after lumbar disc surgery. The study was done
      as a single blinded randomized clinical trial. From 60 patients who underwent
      lumbar disc surgery, 30 subjects were placed in isoflurane group and 30 in the
      TIVA group. Maintenance of anesthesia was done with isoflurane (MAC=0.8-1) and
      N(2)O 50% in isoflurane group and in TIVA group with propofol at the dose of 100
      150 mg /kg body weight /minute and remifentanil at the dose of 2.0 mg /kg body
      weight/minute. Chills rate was recorded in recovery room. Changes in body
      temperature, body surface temperature, systolic blood pressure, diastolic blood
      pressure and heart rate showed no significant difference between the two groups
      before and after induction and at different times during the operation (P<0.05).
      Chill rate was not significantly different between the two groups (P<0.05). It
      seems that TIVA (remifentanil at the dose of 2.0 ug/kg body weight/minute in
      combination with propofol at the dose of 100-150 ug/kg body weight/minute) and
      0.81 MAC isoflurane-N(2)O 50% can be used as a safe method of anesthesia in
      patients with good tolerance lumbar back disc surgery without hypothermia, chills
      and considerable hemodynamic changes.

PMID- 21960074
TI  - Dopaminergic activity in the medial prefrontal cortex modulates fear
      conditioning.
AB  - The purpose of the present study was to determine the role of medial prefrontal
      cortex (mPFC) dopaminergic system in fear conditioning response considering
      individual differences. Animals were initially counterbalanced and classified
      based on open field test, and then were given a single infusion of the dopamine
      agonist, amphetamine (AMPH) and antagonist, clozapine (CLZ) into the medial
      prefrontal cortex. Rats received tone-shock pairing in a classical fear
      conditioning test and then exposed to the tone alone. Freezing responses were
      measured as conditioned fear index. The results showed that both AMPH and CLZ
      infusion in mPFC reduced the expression of conditioned fear. This finding
      indicates that elevation or reduction in the dopaminergic activity is associated
      with the decrease of fear responses, despite preexisting individual-typological
      differences.

PMID- 21960075
TI  - Pituitary function impairment after moderate traumatic brain injury.
AB  - To determine the prevalence of pituitary hormone deficiencies after moderate
      traumatic brain injury (TBI). We conducted a prospective cohort and included 75
      patients with moderate TBI with GCS between 9 and 13 who referred to emergency
      department of Shariati Hospital, Tehran/Iran, during 2004-2007. Pituitary
      hormones were assessed 3 and 6 months after injury. In 3(rd) month post-injury,
      39 cases had not any pituitary dysfunction; however, deficiencies in one, two and
      three of the pituitary hormones were found in 26, 8 and 2 patients, respectively.
      Twenty one patients showed a deficiency in one of the pituitary hormones and only
      one case with deficiency of two after 6 months. The most prevalent changes occur
      in IGF-1 and LH/FSH after moderate TBI. However, the whole deficiencies decrease
      over the time.

PMID- 21960076
TI  - Association of the serum glucose level with fetal-maternal complications of
      gestational diabetes with insulin therapy.
AB  - Gestational diabetes mellitus (GDM) is one of the important problems in pregnant
      women. This study conducted to determine association the level of serum glucose
      with fetal-maternal complications of gestational diabetes with insulin therapy.
      This study has been conducted as an Existing Data Study, so medical records of
      all pregnant women with GDM that have been treated with insulin during 2 years of
      study has been selected using census. The information was obtained using, medical
      records data. Mean level of serum glucose before and after treatment in different
      times according to correct level of serum glucose did not show statistical
      significant (P>0.05). Apgar score, time of stay in NICU, weight at the birth,
      base on correct level of serum glucose did not show statistical significant
      (P>0.05). Gestational age at the delivery, stay in hospital, diagnosis and fetal
      maternal complications between two groups did not show statistical significant
      (P>0.05). It seems we can with screening and diagnostic GDM with suitable control
      of level of serum glucose and insulin therapy reduce incidence of fetal-maternal
      complications.

PMID- 21960077
TI  - Leukocyte count and erythrocyte sedimentation rate as diagnostic factors in
      febrile convulsion.
AB  - Febrile convulsion (FC) is the most common seizure disorder in childhood. white
      blood cell (WBC) and erythrocyte sedimentation rate (ESR) are commonly measured
      in FC. Trauma, vomiting and bleeding can also lead to WBC and ESR so the blood
      tests must carefully be interpreted by the clinician. In this cross sectional
      study 410 children(163 with FC), aged 6 months to 5 years, admitted to Bahrami
      Children hospital in the first 48 hours of their febrile disease, either with or
      without seizure, were evaluated over an 18 months period. Age, sex, temperature;
      history of vomiting, bleeding or trauma; WBC, ESR and hemoglobin were recorded in
      all children. There was a significant increase of WBC (P<0.001) in children with
      FC so we can deduct that leukocytosis encountered in children with FC can be due
      to convulsion in itself. There was no significant difference regarding ESR
      (P=0.113) between the two groups. In fact, elevated ESR is a result of underlying
      pathology. In stable patients who don't have any indication of lumbar puncture,
      there's no need to assess WBC and ESR as an indicator of underlying infection. If
      the patient is transferred to pediatric ward and still there's no reason to
      suspect a bacterial infection, there is no need for WBC test.

PMID- 21960078
TI  - Sensitivity and specificity of international prostate symptom score (IPSS) for
      the screening of Iranian patients with prostate cancer.
AB  - We assessed the lower urinary tract symptoms (LUTS) in prostatic cancer patients
      and investigated the sensitivity and specificity of international prostate
      symptom score (IPSS) in the screening of these patients. A total number of 132
      prostatic cancer patients as the case group who were confirmed by the
      pathologists and 101 noncancerous men as the control group, aged 50 or older,
      responded to a questionnaire which included seven questions regarding urination,
      named the International Prostate Symptom Score (IPSS). Then, two groups were
      assessed and compared with each other and also the sensitivity and specificity of
      IPSS tool for screening of prostatic cancer patients were calculated. All
      participants filled out the questionnaire. 60 (59.4%) noncancerous men and 29
      (22.0%) cases had mild LUTS, and 41 (40.6%) noncancerous men and 103 (78.0%)
      cases had moderate to severe LUTS. Moreover, the sensitivity and specificity of
      the IPSS tool were 78% and 59.4%, respectively. Urination status and problems
      could be easily assessed by IPSS and it is a sensitive and specific tool for
      screening of prostatic cancer patients. It appears that IPSS is a cost
      beneficial, sensitive, specific and easily-used screening tool to diagnose the
      prostate cancer cases. Therefore, it can be used more extensively by the health
      care providers as well as by men >=50 years old themselves.

PMID- 21960079
TI  - Outcome of continuous intrathecal opioid therapy for management of chronic pain
      in Iranian veterans of the imposed Iraq- Iran war.
AB  - Among patients with chronic unrelieved pain, war veterans of eight years long
      Iraq - Iran war deserve especial attention. They not only suffer from severe
      intractable pain but also should bear some intangible consequences of unrelieved
      pain and severe disability. This perspective study reviews the outcome of
      implantation of intrathecal opioid pumps in these patients. Ten war veterans
      (mean age 43.36) with chronic nonmalignant pain included in this perspective
      study. Medical records reviewed to identify pain diagnosis, medication intake
      prior to implantation, details of the intrathecal opioid trial and date of
      implantation, surgical and technical complications. Outcome measures were global
      pain relief, physical activity levels, intrathecal opioid side effects,
      medication consumption and patient satisfaction. Overall pain relief at the time
      of study was 60%. Mean pain relief was 53%. A majority of patients reported
      improvements in physical activity levels and were satisfied with this type of
      therapy. Impotence and constipation were two most common pharmacological side
      effects. No surgical complication reported. The study showed that this type of
      therapy in Iranian war veterans improved analgesia, increased self-report
      physical activity levels and in spite of high incidence of pharmacological side
      effects, most of the patients were satisfied with this type of therapy. These
      results are comparable to those of previous studies in this field.

PMID- 21960080
TI  - Evaluation of bone mineral density in Iranian HIV/AIDS patients.
AB  - Bone disorders have emerged as a worrisome complication in HIV-infected patients
      in recent years. It is not clear that HIV infection itself or antiretroviral
      treatment or both are causes of bone loss. However, most studies have found a
      high prevalence of osteopenia and osteoporosis in HIV/AIDS patients. The
      objectives of this study were to determine the prevalence of osteopenia and
      osteoporosis in HIV-infected patients either untreated or receiving Highly Active
      Antiretroviral Therapy as compared with HIV negative persons. We also assessed
      the factors associated with these conditions. Bone Mineral Density was assessed
      by Dual Energy X-Ray Absorptiometry scans at the hip and lumbar spine in 36 AIDS
      patients receiving antiretroviral therapy and 44 HIV infected patients not
      receiving antiretroviral therapy (naive patients) and 40 HIV negative individuals
      as control. Factors that affect BMD were also determined. Prevalence of
      osteopenia or osteoporosis in different regions was significantly higher in
      HIV/AIDS patients compared with HIV negative subjects (77.3% in HIV positive
      naive patients, 86.1% in HAART-treated patients and 60% in the control group,
      P=0.002). Mean serum alkaline phosphatase was higher in HIV/AIDS patients than
      the control group (P=0.003). Osteopenia and osteoporosis in HIV-infected patients
      were associated with duration of HIV infection (P<0.0001) and antiretroviral
      treatment (P=0.012). Prevalence of osteopenia and osteoporosis in HIV/AIDS
      patients was higher than HIV negative individuals. Osteopenia and osteoporosis in
      HIV/AIDS patients was associated with duration of HIV infection and
      antiretroviral treatment.

PMID- 21960081
TI  - Dietary intakes in asthmatic and non-asthmatic female pupils of Tehran.
AB  - Dietary factors are suggested to be involved in recent increases in the
      prevalence of asthma. The differences in dietary intake of 23 asthmatic and 317
      non-asthmatic students were investigated, who were chosen by multistage
      stratified cluster sampling. The dietary data were assessed by food frequency
      questionnaire and a 24-h recall form. Total calorie and fat intake were similar.
      Daily intake of Saturated and poly-unsaturated fatty acids, and calcium and
      sodium were significantly higher in asthmatics. There was no significant
      difference between dietary antioxidant intake of asthmatic and non asthmatics. It
      seems that in this age, the type of consumed fat may be more important than the
      amount of fat intake in inducing asthma. For accurate results, n-6 and n-3 fatty
      acid intake must be assessed. Higher sodium and calcium intake may also be
      associated with asthma. Randomized controlled trials with restricting diets can
      help to elucidate the results.

PMID- 21960082
TI  - Description of some dermatoscopic features of acral pigmented lesions in Iranian
      patients: a preliminary study.
AB  - Proper differentiation between acral malignant melanoma and benign pigmented
      lesions like melanocytic nevi is of great value. To avoid unnecessary biopsies,
      dermatoscopy has been introduced as a non-invasive modality and has improved the
      clinical diagnostic accuracy in recent decades. We aimed to describe dermoscopic
      patterns of acral pigmented lesions of patients in the clinic of dermatology in
      Razi Hospital, Tehran, Iran. This study was conducted as a descriptional study
      among a total of 62 pigmented lesions located on volar skin of palms and soles.
      After initial clinical evaluation, lesions were examined entirely by dermoscopy.
      All the patterns within a lesion were described, and lesions suspicious of
      malignancy (clinically or dermatoscopically) were selected for histopathological
      evaluation. Of our 62 lesions, three lesions were not melanocytic. According to
      our final clinicopathological diagnosis, 47 lesions were benign melanocytic nevi
      and 12 lesions were malignant melanoma. Parallel furrow pattern was the most
      frequent among our benign lesions (51.1%) followed by lattice-like pattern
      (23.4%) and acral reticular pattern (21.3%). Diffuse multi-component pattern,
      parallel ridge pattern and abrupt edge were respectively most common patterns
      among malignant melanomas. Acral benign melanocytic nevi and malignant melanomas
      respectively have well distinctive characteristics in dermatoscopy among our
      patients.

PMID- 21960083
TI  - Assessing the prevalence of HIV among Afghan immigrants in Iran through rapid HIV
      testing in the field.
AB  - Throughout the world, many migrant and mobile populations are at elevated risk
      for HIV. Iran has a large immigrant population from neighboring Afghanistan;
      however, few data exist on the prevalence of HIV in this community. In 2008, we
      conducted a study to assess the presence of HIV infection among 477 immigrants in
      a town to the northeast of Tehran using a rapid test in the field. HIV prevalence
      was 0.2% (95% CI 0.005-1.2) with one person HIV-positive. We recommend periodic
      HIV sero-surveillance with detailed behavioral measures for this population in
      the future.

PMID- 21960084
TI  - Neurofibroma of the sciatic nerve with neurofibromatosis type 1.
AB  - A 28-year-old man with neurofibromatosis type 1(NF1) presented with a tumor in
      the sciatic nerve and femoral nerve. The differential diagnosis of malignant
      peripheral nerve sheath tumor was based on clinical, radiological, and
      histological evidence. The tumor apparently originated in sciatic nerve at the
      posterior aspect of the left thigh. The lesion was resected totally without
      neural damage to the sciatic nerve. The tumor did not recur after 2 years.

PMID- 21960085
TI  - A 75-year old man complaining of flank pain and obstructive urinary symptoms: a
      case report.
AB  - Benign renal cystic adenoma with out malignant features is a very rare entity. A
      75 year old male with obstructive Lower tract symptoms and vague flank pain was
      admitted and planned for nephrectomy of non functional kidney -due to long term
      nephrolithiasis- intra operative finding was a cystic hydronephrotic kidney
      filled by thick mucous secretions which turned out to be a cyst adenoma of kidney
      with no malignant features.

PMID- 21960086
TI  - Caffeine's effect on intermittent sprint cycling performance with different rest
      intervals.
AB  - The purpose of this study was to investigate the effects of caffeine ingestion on
      the performance of an intermittent sprint cycling test (ISCT) with different rest
      intervals. Fourteen males with team sport experience consumed 6 mg kg(-1) of
      caffeine or a placebo 60 min prior to completing two sets of an ISCT with 4-min
      rest intervals. Each set consisted of 12 * 4-s sprints with 20- or 90-s active
      recovery intervals at 60-70 rpm. Blood lactate was collected at baseline and
      immediately following the completion of six sprints in each set. At 20-s recovery
      intervals, peak power and total work were not significantly different between
      conditions during the ISCT (P > 0.05); but caffeine reduced 6.31% effort for mean
      power in Sprint 10 of the later stage, as well as an increased fatigue index and
      elevated blood lactate levels during the ISCT (P < 0.05). At 90-s recovery
      intervals, peak power, mean power, and total work under caffeine conditions were
      significantly higher than under placebo conditions during the ISCT (P < 0.05),
      but no differences were apparent in fatigue index and blood lactate levels (P >
      0.05). In conclusion, caffeine ingestion may be ergolytic, affecting performance
      and fatigue development in the later stage during a prolonged and intermittent
      sprint test with a short recovery interval. However, caffeine produces an
      ergogenic effect in the initial stage of an intermittent sprint performance with
      a longer recovery interval.

PMID- 21960087
TI  - How well does serum bicarbonate concentration predict the venous pH in children
      being evaluated for diabetic ketoacidosis?
AB  - OBJECTIVE: The objective of the study was to determine whether serum bicarbonate
      (HCO3) concentration can accurately predict venous pH in the evaluation of
      diabetic ketoacidosis (DKA). METHODS: A retrospective review of patients who
      presented to a children's hospital emergency department and received an
      International Classification of Diseases, Ninth Revision code related to DKA or
      diabetes mellitus was performed. To be eligible for inclusion and data
      abstraction, patients had blood sampled simultaneously for venous blood gas and
      metabolic panel. A linear regression model was created using pH (dependent
      variable) and HCO3 (predictor). The diagnostic performance and accuracy of HCO3
      to discriminate abnormal pH were evaluated using receiver operating
      characteristic curve analysis. RESULTS: Three hundred patients met the inclusion
      criteria. The linear relationship between pH and HCO3 using the Pearson
      correlation coefficient was found to be R = 0.89 (confidence interval [CI], 0.83
      0.95; R = 0.79). Receiver operating characteristic curve analysis that maximized
      sensitivity and specificity demonstrated that a HCO3 18.5 or less predicts pH
      less than 7.3 (area under the curve = 0.97; CI, 0.94-0.99; sensitivity, 93%;
      specificity, 91%), and a HCO3 10.5 or less predicts pH less than 7.1 (area under
      the curve = 0.97; CI, 0.95-0.99; sensitivity, 97%; specificity, 88%).
      CONCLUSIONS: Serum bicarbonate accurately predicts abnormal venous pH in children
      with DKA. Venous pH determination may not be necessary for all patients being
      evaluated for DKA.

PMID- 21960088
TI  - Organized interfacility transfer processes: an opportunity to improve pediatric
      emergency care.
AB  - OBJECTIVE: The objective of the study was to determine the proportion of
      hospitals with established guidelines and agreements for the interfacility
      transfer of seriously ill and injured children. METHODS: Paper- and Web-based
      survey tools were utilized by states to survey all hospitals with an emergency
      department. In addition, a content analysis was done on existing state mandates
      and regulations addressing interfacility transfer guidelines/protocols and
      agreements. RESULTS: Thirty-six states/territories participated in the Web
      survey. Two-thousand fifty-one or 62% of hospitals returned the surveys. Although
      54% of responding facilities had interfacility transfer guidelines, only 42% of
      facilities included language regarding transfer of children. Only 13% of
      hospitals had interfacility guidelines containing all recommended components. No
      defined interfacility transfer processes or guidelines were in place in 46% of
      the data-set hospitals.Responding hospitals had agreements for transfer of
      patients requiring specialty services only 59% of the time, although only 43% of
      agreements included language specific to pediatrics. Interfacility transfer
      agreements were lacking in 41% of responding facilities.Fourteen states have
      legislative mandates requiring interfacility transfer guidelines and agreements.
      Enactment of state mandates for interfacility transfer agreements and guidelines
      may influence this process, although these data do not support this, and more
      research is needed. CONCLUSIONS: Organized processes for interfacility transfer
      of ill or injured children were not established for a sizable proportion of
      survey hospitals. Addressing this void may provide an opportunity to improve the
      emergency care of children.

PMID- 21960089
TI  - Intussusception: postreduction fasting is not necessary to prevent complications
      and recurrences in the emergency department observation unit.
AB  - OBJECTIVES: This study aimed to compare the incidence of complications and
      intussusception recurrences in patients in the pediatric emergency department
      observation unit (EDOU) who are fed early (< 2 hours) versus late (>= 2 hours)
      after radiologic intussusception reduction. METHODS: This is a retrospective
      cohort study of children observed in the Texas Children's Hospital EDOU after
      radiologic intussusception reduction between April 1, 2003, and August 31, 2009.
      Complications were defined as the postreduction occurrence of intestinal
      perforation, shock, or sepsis. RESULTS: There were 149 patients included in the
      study (median age, 16 months; range, 3-95 months). Oral refeeding was started
      early in 61 patients (41%) and late in 88 patients (59%). The median length of
      EDOU stay was 15.6 hours in early refeeders and 16.1 hours in late refeeders (P =
      0.58). None of the patients developed any complications. There was no difference
      in the frequency of postreduction fever, abdominal pain, or vomiting (13% early
      vs 16% late, P = 0.65); imaging to assess for intussusception recurrence (20%
      early vs 22% late, P = 0.79); and subsequent hospitalization (3% early vs 8%
      late, P = 0.31) between the groups. The frequency of intussusception recurrence
      was higher, but not significantly so (P = 0.31), in the late refeeders (15%)
      compared with the early refeeders (8%). CONCLUSIONS: There is no evidence for a
      difference in complication frequency, intussusception recurrence, or EDOU length
      of stay between patients who are fed early (< 2 hours) or late (>= 2 hours) after
      radiologic intussusception reduction. This indicates that there is no need to
      withhold feeds from patients after intussusception reduction.

PMID- 21960090
TI  - Reducing contamination of peripheral blood cultures in a pediatric emergency
      department.
AB  - OBJECTIVE: Blood culture contamination rates (CRs) in emergency departments (EDs)
      vary from 1% to 9% in previous studies. High CRs cause unnecessary admissions,
      antibiotics, and costs. Different measures have been tried to improve CR. This
      study sought to determine the ED CR at Arkansas Children's Hospital (ACH) and
      evaluate an educational intervention. DESIGN: A slide presentation of the ACH's
      blood culture collection procedure was made. The ED nursing staff viewed this
      individually and demonstrated the procedure on a mock extremity. Data before
      (from June 1 to November 30, 2007; PRE) and after (from February 1 to July 31,
      2008; POST) intervention regarding blood cultures positive for organism submitted
      to the ED and any descriptive data were collected retrospectively. Descriptive
      statistics described the CR, positivity rate (PSR), and pathogen rate (PR).
      Frequent collectors were identified as those submitting more than 72 blood
      cultures during PRE and during POST. Contamination rate in frequent collectors
      was independently assessed for improvement. This study was approved by the
      institutional review board of the University of Arkansas for Medical Sciences.
      RESULTS: Positivity rate during PRE was 6.8% (n = 15; 95% confidence interval
      [CI], 2.9-10.7); 114 were contaminants (CR, 5.0%; 95% CI, 1.04-8.98) and 40 were
      pathogens (PR, 1.8%; 95% CI, +/- 4.28). Positivity rate during POST was 6.3% (n =
      157; 95% CI, 2.6-10.0); 124 were contaminants (CR, 4.9%; 95% CI, 1.14-8.66) and
      33 were pathogens (PR, 1.4%; 95% CI, +/- 4.22). For both PRE and POST,
      contaminants represented 74% or greater of all the positives and more than 75% of
      contaminants occurred in patients 0 to 36 months old.Contamination rates of
      individual practitioners ranged from 0% to 17% (PRE) and from 0% to 21% (POST).
      The CR was lower in POST for samples submitted from frequent collectors
      (practitioners submitting >72 blood cultures per study period, n = 6), was
      evaluated separately, and found to improve in POST (from 4.1% to 2.7%). A t test
      for matched samples for these samplers revealed a significant decrease in the
      POST period, P = 0.03. CONCLUSIONS: The CR in the ACH ED for peripherally drawn
      blood cultures is approximately 5% monthly with less than 2% PR. For each culture
      positive for organism, the chance of contamination is 75% or higher. An
      intervention emphasizing the appropriate technique, monitored training, and
      improved CR of a group of frequent collectors is warranted.

PMID- 21960091
TI  - Emergency department crowding and analgesic delay in pediatric sickle cell pain
      crises.
AB  - OBJECTIVES: The objectives of the study were to test the impact of emergency
      department (ED) crowding and to identify factors associated with delay in
      analgesic administration in pediatric sickle cell pain crises. METHODS: This was
      a cross-sectional study at a children's hospital ED. Data included demographics,
      clinical features, triage acuity, 10-level triage pain score, and arrival-to
      analgesic-administration time. Emergency department census was the crowding
      measure assigned to each patient at arrival. Severe pain was a triage pain score
      of more than 7. Delays of more than 60 minutes from arrival to analgesic
      administration represented poor care. Logistic regression tested the effect of ED
      census on time to analgesic administration after adjusting for patient
      demographic and clinical characteristics. RESULTS: From 243 encounters (161
      patients), we excluded 11 visits (missing charts [n = 7], no pain at triage [n =
      3], analgesic refusal [n = 1]). Final analysis involved 232 encounters (150
      patients). Most were black with hemoglobin SS. Median age was 12 years. Mean ED
      census was 57. Median time from arrival to analgesic administration was 90
      minutes. Analgesics were administered in less than 60 minutes in 70 encounters
      (30%). Most delays occurred after triage. Univariate analysis revealed that
      analgesic administration within 60 minutes of arrival was associated with severe
      pain at triage. After controlling for other factors, analgesic administration was
      significantly delayed during higher ED census and significantly earlier for young
      children and those with severe pain at triage. The time to analgesic
      administration from arrival significantly increased per increasing quartile of ED
      census (P = 0.0009). CONCLUSION: Emergency department crowding is associated with
      delay in analgesic administration in pediatric patients with sickle cell pain
      crisis.

PMID- 21960092
TI  - Intraosseous line use, complications, and outcomes among a population-based
      cohort of children presenting to California hospitals.
AB  - OBJECTIVES: Intraosseous line (IO) use has been described in prehospital
      settings, with some studies in the emergency department (ED). However, population
      based studies describing IO line use across diverse ED and hospital settings are
      sparse, and the true incidence of complications remains unknown. METHODS: This
      was a retrospective cohort study using administrative data from 450 California
      hospitals and EDs. We included all children aged 0 to 18 years with ED or
      inpatient visits from 2005 through 2007. CPT (Current Procedural Terminology) and
      ICD-9 (International Classification of Diseases, Ninth Revision) codes were used
      to identify IO line use. ICD-9 diagnosis codes were searched for potential
      complications related to IO line use including compartment syndrome, fracture,
      and osteomyelitis. Descriptive statistics were used to calculate incidence of
      use, outcomes, and hospital setting with IO line use. RESULTS: Two hundred ninety
      one children had IO lines placed in 90 hospitals, including 239 in the ED and 52
      inpatient. There were 6,660,564 pediatric ED visits and 2,276,231 pediatric
      admissions, resulting in an incidence of IO line placement of 0.04 per 1000 ED
      visits and 0.02 per 1000 admissions. Mortality was 37% among patients with IO
      line placement. The most common diagnoses included cardiac arrest (34%), trauma
      (19%), and respiratory failure (6%). Types of hospital in which IO lines were
      placed included children's hospitals 14%, general hospitals 86%, and rural
      hospitals 7.9%. No complications were identified. CONCLUSIONS: The overall
      incidence of IO line use in the ED and hospital setting is low, but IO line
      access is used in a variety of different hospital and ED settings for high-acuity
      conditions. No IO line complications were identified.

PMID- 21960093
TI  - Incidence and recognition of elevated triage blood pressure in the pediatric
      emergency department.
AB  - OBJECTIVES: This study aimed to determine the incidence of elevated triage blood
      pressure (BP) in pediatric emergency patients and to evaluate its recognition by
      health care practitioners. METHODS: This retrospective review randomly selected
      patients seen in a large academic pediatric emergency department for 13 months.
      Triage and subsequent BP measurements were recorded and categorized as normal or
      elevated (>= 90th to < 95th, >= 95th-99th percentile plus 4 mm Hg, and >= 99th
      percentile plus 5 mm Hg). Physician recognition of elevated BP, training level,
      and specialty were collected. Demographic information and possible confounding
      variables (weight, pain, medications, and triage level) were also collected and
      analyzed. Exclusions included known hypertension or related conditions and those
      patients without a triage BP measurement. RESULTS: Of the 978 charts reviewed,
      907 were included for study (17.5% infants, 82.5% children 1 year and older to 18
      years; 50% male, 50% female; 77% African American, 16% white, 4% Hispanic, and 3%
      other). Fifty-five percent (n = 497) had elevated triage BP (>= 90th percentile)
      with only 1% (n = 7) recognized by practitioners as having elevated triage BP.
      Further, 152 (20%) of the 748 children 1 year and older to 18 years had severely
      elevated BP with only 5 recognized. CONCLUSIONS: In this study, more than half of
      the patients had elevated triage BP (>= 90th percentile), which was rarely
      recognized by emergency department practitioners regardless of specialty or
      experience. Early recognition of elevated triage BP offers opportunities for
      diagnosis of hypertension and related disorders but is challenging to accomplish.

PMID- 21960094
TI  - Serial cardiac troponin concentrations as marker of cardiac toxicity in children
      with status asthmaticus treated with intravenous terbutaline.
AB  - OBJECTIVES: The study's objectives were to evaluate serial troponin
      concentrations as a marker of cardiac toxicity in children receiving intravenous
      terbutaline for status asthmaticus and to study if troponin concentrations are
      affected by severity of asthma and risk factors for severe asthma. METHODS: This
      was a prospective observational study in 20 consecutive patients who were
      admitted to a tertiary care pediatric intensive care unit for status asthmaticus
      and received intravenous terbutaline. Cardiac troponin I (cTnI) concentrations
      were measured half an hour before the bolus of intravenous terbutaline, 4 hours
      after terbutaline, and then every 24 hours until discontinuation of the
      continuous terbutaline infusion. RESULTS: Ten patients had cTnI concentrations
      greater than 0.03 ng/mL. Maximum cTnI concentrations were recorded after the
      terbutaline bolus in 6 patients, during terbutaline infusion in 3 patients, and
      before terbutaline use in 1 patient. Three of these 10 (3/10) patients showed
      increased cTnI concentrations before the terbutaline bolus. One patient had a
      significant elevation in cTnI concentration (peak level of 3.79 ng/mL) with
      electrocardiogram (ECG) changes of myocardial injury that normalized upon
      discontinuation of terbutaline. All other patients with elevated cTnI
      concentrations had normal ECG findings. CONCLUSIONS: Elevated cTnI concentrations
      were observed in 50% of patients treated with intravenous terbutaline for status
      asthmaticus. Clinically significant cardiotoxicity was not observed except in 1
      patient in whom the abnormal ECG findings normalized upon discontinuation of
      terbutaline. There was no statistically significant difference in asthma severity
      or in the risk factors for severe asthma in children with and without elevation
      of cTnI concentrations.

PMID- 21960095
TI  - Child abuse education: an objective evaluation of resident and attending
      physician knowledge.
AB  - OBJECTIVE: The objective of the study was to evaluate residents' and practicing
      physicians' medical knowledge of child abuse and maltreatment. METHODS: In a
      freestanding pediatric hospital and community hospital, a 30-question survey was
      administered to pediatric residents, general pediatricians (GPs), and pediatric
      emergency medicine (PEM) physicians. The institution's child protection team
      developed the questions, which were pilot tested for validity. Question content
      covered major concepts in child abuse and neglect. Information on previous
      training of child abuse was also collected. RESULTS: There were 95 respondents,
      64.2% (n = 61) were residents, 19% (n = 18) were GPs, and 16.8% (n = 16) were PEM
      physicians. Overall, the average score was 63.3% (SD, 13.8%). There was a
      statistically significant difference in the knowledge of child abuse and neglect
      across physician categories (P < 0.001). Pediatric emergency medicine physicians
      scored the highest (76.9 [SD, 9.1]) compared with GPs (66.7 [SD, 12.4]; P =
      0.018) and pediatric residents (60.4 [SD, 12.9]; P < 0.001). There was no
      difference in the level of knowledge across residency training years (P = 0.076).
      CONCLUSIONS: With a mean score in our study of 63.3%, there appears to be an
      overall lack of knowledge in child abuse. These findings highlight the need for
      increased education in child maltreatment.

PMID- 21960096
TI  - Elevated cardiac troponin I level in cases of thoracic nonaccidental trauma.
AB  - BACKGROUND: Injury patterns in nonaccidental trauma (NAT) often include injury to
      the chest. However, signs and symptoms of cardiac insult are often nonspecific
      and may be missed. Evaluation with serum cardiac troponin I (CTnI), a specific
      indicator of myocardial injury, could improve the comprehensive evaluation of
      patients with suspected NAT. OBJECTIVE: The objective of this study was to
      describe the patient characteristics and results of CTnI testing in children with
      thoracic NAT. METHODS: Children presenting to the emergency department were
      included if CTnI was obtained and they had at least one of the following: history
      of blunt trauma to the chest, bruising or abrasions to the chest, or fractures of
      the ribs, sternum, or clavicles. A serum CTnI level above 0.04 ng/mL was
      considered elevated. RESULTS: Ten patients (6 males) with an age range from 2
      months to 4 years (mean [SD], 20 [20] months) were identified during the 17-month
      study period. All patients were evaluated with NAT. Cardiac troponin I level was
      elevated in 7 (70%) of 10 patients with levels between 2 and 50 times the upper
      limit of normal. CONCLUSIONS: This report is the first to document elevation of
      CTnI levels in cases of thoracic NAT. The elevation of the level of this specific
      biomarker may be indicative of sufficient chest trauma to result in the heart
      being injured, independent of the presence of cardiac decompensation or shock
      from other causes. Prospective evaluation of the forensic and clinical use of
      CTnI in this population is warranted.

PMID- 21960097
TI  - What is an autotroph?
AB  - The concept of autotrophy depends on the growth media for pure cultures supplying
      a single one carbon source for anabolism. Secondary carbon compounds added to the
      medium as chelators and/or vitamins confuse the meaning. This note suggests a
      clarification of definition suitable for contemporary biochemical studies of true
      autotrophs.

PMID- 21960099
TI  - [Stem cell properties of therapeutic potential].
AB  - Stem cell research is a innovative technology that focuses on using
      undifferentiated cells able to self-renew through the asymmetrical or symmetrical
      divisions. Three types of stem cells have been studied in laboratory including
      embryonic stem cell, adult stem cells and induced pluripotent stem cells.
      Embryonic stem cells are pluripotent stem cells derived from the inner cell mass
      and it can give rise to any fetal or adult cell type. Adult stem cells are
      multipotent, have the ability to differentiate into a limited number of
      specialized cell types, and have been obtained from the bone marrow, umbilical
      cord blood, placenta and adipose tissue. Stem cell therapy is the most promising
      therapy for several degenerative and devastating diseases including digestive
      tract disease such as liver failure, inflammatory bowel disease, Celiac sprue,
      and pancreatitis. Further understanding of biological properties of stem cells
      will lead to safe and successful stem cell therapies. (Korean J Gastroenterol
      2011;58: 125-132).

PMID- 21960098
TI  - Glycoprotein production in moss bioreactors.
AB  - Complex multimeric recombinant proteins such as therapeutic antibodies require a
      eukaryotic expression system. Transgenic plants may serve as promising
      alternatives to the currently favored mammalian cell lines or hybridomas. In
      contrast to prokaryotic systems, posttranslational modifications of plant and
      human proteins resemble each other largely, among those, protein N-glycosylation
      of the complex type. However, a few plant-specific sugar residues may cause
      immune reactions in humans, representing an obstacle for the broad use of plant
      based systems as biopharmaceutical production hosts. The moss Physcomitrella
      patens represents a flexible tissue-culture system for the contained production
      and secretion of recombinant biopharmaceuticals in photobioreactors. The recent
      synthesis of therapeutic proteins as a scFv antibody fragment or the large and
      heavily modified complement regulator factor H demonstrate the versatility of
      this expression system. A uniquely efficient gene targeting mechanism can be
      employed to precisely engineer the glycosylation machinery for recombinant
      products. In this way, P. patens lines with non-immunogenic optimized glycan
      structures were created. Therapeutic antibodies produced in these strains
      exhibited antibody-dependent cellular cytotoxicity superior to the same molecules
      synthesized in mammalian cell lines.

PMID- 21960100
TI  - [Preclinical experience in stem cell therapy for digestive tract diseases].
AB  - Adult stem cells are multipotent and self-renewing cells that contain several
      functions; i) migration and homing potential: stem cells can migrate to injured
      and inflamed tissues. ii) differentiation potential: stem cells which migrated to
      injured tissues can be differentiated into multiple cell types for repairing and
      regenerating the tissues. iii) immunomodulatory properties: stem cells,
      especially mesenchymal stem cells can suppress immune system such as
      inflammation. All those characteristics might be useful for the treatment of the
      digestive tract diseases which are complex and encompass a broad spectrum of
      different pathogenesis. Preclinical stem cell therapy showed some promising
      results, especially in liver failure, pancreatitis, sepsis, and inflammatory
      bowel disease. If we can understand more about the mechanism of stem cell action,
      stem cell therapy can become a promising alternative treatment for refractory
      digestive disease in the near future. In this review, we summarized current
      preclinical experiences in diseases of the digestive tract using stem cells.
      (Korean J Gastroenterol 2011;58:133-138).

PMID- 21960101
TI  - [Clinical trials with stem cells in digestive diseases and future perspectives].
AB  - Many techniques for isolation, expansion and handling of stem cells are being
      developed rapidly, and preclinical evidence has shown the possibility to use this
      technology for refractory diseases in the near future. Among refractory digestive
      diseases, Crohn's disease and liver cirrhosis may be two main diseases where stem
      cell therapy can be applied for anti-inflammation and regeneration of tissue.
      Currently, with respect to these two diseases, clinical trials using
      hematopoietic stem cells and mesenchymal stem cells from bone marrow or adipose
      tissue have shown some evidence of clinical benefits to immune modulation,
      suppression of inflammation and regeneration of functional cells. However, for
      the development of practical stem cell therapy, we need more data on underlying
      mechanisms, effective subpopulation of stem cells and its sources, and effective
      parameters for monitoring and estimation. With technical advances, the research
      on embryonic and induced pluripotent stem cells will also contribute to the new
      therapeutic strategies for digestive regenerative medicine. In the future, a
      variety of stem cell therapies may be therapeutic options for refractory
      digestive diseases, but many technical challenges remain to be solved. (Korean J
      Gastroenterol 2011;58:139-143).

PMID- 21960102
TI  - [A case of a neuroendocrine carcinoma in the minor papilla].
AB  - Neuroendocrine tumors are usually found in the ileum, appendix, rectum, colon and
      stomach. Ampullary neuroendocrine tumor is extremely rare and only a few cases of
      neuroendocrine carcinoma of the minor papilla have been reported. The
      preoperative diagnosis is very challenging because either asymptomatic or
      manifests as nonspecific abdominal pain. The tumor is relatively small and
      located at the deep mucosa and submucosa. Endoscopy with deep biopsy, endoscopic
      retrograde cholangiopancreatography and endoscopic ultrasonography are good
      diagnostic tools. The best therapeutic choice is surgery. We report an unusual
      case of a 55-year-old woman who underwent endoscopy as part of a regular health
      checkup and was diagnosed a neuroendocrine carcinoma in the minor papilla, which
      was successfully resected by pancreaticoduodenectomy. (Korean J Gastroenterol
      2011;58:144-148).

PMID- 21960103
TI  - [A case of hepaticoduodenal fistula development after transarterial
      chemoembolization in patient with hepatocellular carcinoma].
AB  - Transarterial chemoembolization (TACE) is recommended as one of the first line
      therapy for unresectable hepatocellular carcinoma (HCC). Rupture of HCC following
      TACE is a rare and potentially fatal complication. We report a case of
      hepaticoduodenal fistula with ruptured HCC and liver abscess complicated by TACE.
      A 52-year-old male was treated by TACE three times, followed by radiation therapy
      and systemic chemotherapy. 30 days after the last TACE, right upper quadrant pain
      of abdomen was developed. About 1 month later, computed tomography of abdomen
      showed ruptured HCC with debris containing liver abscess and hepaticoduodenal
      fistula. Esophagogastroduodenoscopy revealed hepaticoduodenal fistula and hepatic
      parenchyme covered with exudate. The patient was managed with supportive care,
      but the hepaticoduodenal fistula persisted. (Korean J Gastroenterol 2011;58:149
      152).

PMID- 21960104
TI  - [A case of perforated xanthogranulomatous cholecystitis presenting as biloma].
AB  - Xanthogranulomatous cholecystitis is an unusual inflammatory disease of the
      gallbladder characterized by severe proliferative fibrosis and the accumulation
      of lipid-laden macrophages in areas of destructive inflammation. Its macroscopic
      appearance may occasionally be confused with gallbladder carcinoma. We present a
      case of perforated xanthogranulomatous cholecystitis presenting as biloma. An 80
      year-old woman was referred to our hospital with a 1-week history of abdominal
      pain and febrile sensation. Abdominal CT showed a biloma in the subhepatic area.
      The follow-up CT showed that the biloma increased in size. Therefore,
      ultrasonography-guided aspiration was performed. The aspirated fluid/serum
      bilirubin ratio was greater than 5, which was strongly suggestive of bile leakage
      complicated by perforated cholecystitis. She underwent a laparoscopic
      cholecystectomy with cyst aspiration and adhesiolysis. A histological diagnosis
      of perforated xanthogranulomatous cholecystitis was made.

PMID- 21960105
TI  - [Involvement of splenic hemangioma and rectal varices in a patient with klippel:
      trenaunay syndrome].
AB  - Klippel - Trenaunay syndrome (KTS) is characterized by a cutaneous vascular nevus
      of the involved extremity, bone and soft tissue hypertrophy of the extremity and
      venous malformations. We present a case of KTS with splenic hemangiomas and
      rectal varices. A 29-year-old woman was referred for intermittent hematochezia
      for several years. She had history with a number of operations for cutaneous and
      soft tissue hamangiomas since the age of one year old and for increased
      circumference of her left thigh during the last few months. Abdominal CT revealed
      multiple hemangiomas in the spleen, fusiform aneurysmal dilatation of the deep
      veins and soft tissue hemangiomas. There was no evidence of hepatosplenomegaly or
      liver cirrhosis. Colonoscopy revealed hemangiomatous involvement in the rectum.
      There were rectal varices without evidence of active bleeding. Upon venography of
      the left leg, we also found infiltrative dilated superficial veins in the
      subcutaneous tissue and aneurysmal dilatation of the deep veins. The patient was
      finally diagnosed with KTS, and treated with oral iron supplementation only,
      which has been tolerable to date. Intervention or surgery is not required. When
      gastrointestinal varices or hemangiomatous mucosal changes are detected in a
      young patient without definite underlying cause, KTS should be considered.

PMID- 21960106
TI  - [Right hepatectomy in a patient with hepatocellular carcinoma after induction of
      hepatic parenchymal atrophy through subsequent portal and hepatic vein
      embolizations].

PMID- 21960108
TI  - Reactions of an organoruthenium anticancer complex with 2-mercaptobenzanilide--a
      model for the active-site cysteine of protein tyrosine phosphatase 1B.
AB  - The organometallic anticancer complex [(eta(6)-p-cymene)Ru(en)Cl]PF(6) (1, en =
      ethylenediamine) readily reacts with thiols and forms stable sulfenate/sulfinate
      adducts which may be important for its biological activity. Protein tyrosine
      phosphatase 1B (PTP1B), a therapeutic target, contains a catalytic cysteinyl
      thiol and is involved in the regulation of insulin signaling and the balance of
      protein tyrosine kinase activity. On oxidation, the catalytic Cys215 can form an
      unusual sulfenyl-amide intermediate which can subsequently be reduced by
      glutathione. Here we study reactions of 1 with 2-mercaptobenzanilide, 2, a
      recognized model for the active site of PTP1B. We have characterized
      crystallographically compound 2 and its oxidized sulfenyl-amide derivative 2
      phenyl-1,2-benzisothiazol-3(2H)-one (4), which shows a close structural
      similarity to the sulfenyl-amide in oxidized PTP1B. At pH 7.4 and 5.3, 1 reacted
      with 2, affording a mono-ruthenium thiolato complex [(eta(6)-cym)Ru(en)(S-RS)](+)
      (7(+), R = (C(6)H(4))CONH(C(6)H(5))) and a triply-S-bridged thiolato complex
      [((eta(6)-cym)Ru)(2)(MU-S-RS)(3)](+) (8(+)), respectively. Coordination of Ru to
      the S atom in 7 allows formation of a strong H-bond (2.02 A) between the en-NH
      and the carbonyl oxygen. To assess the possible effect of ruthenium coordination
      on the redox regulation of PTP1B, reactions of these thiolato products with
      H(2)O(2) and/or GSH were then investigated, demonstrating that coordination to Ru
      largely retards both the oxidation (deactivation) of the thiol in compound 2 by
      H(2)O(2) and the subsequent reduction (reactivation) of the sulfenyl-amide by
      GSH, implying that the inhibition of complex 1 on PTP1B (IC(50) of 19 MUM) may be
      attributed to coordination to its catalytic cysteine.

PMID- 21960109
TI  - Plant cell harakiri--programmed cell death in development.

PMID- 21960110
TI  - CD24 Ala57Val polymorphism predicts pathologic complete response to sequential
      anthracycline- and taxane-based neoadjuvant chemotherapy for primary breast
      cancer.
AB  - Overexpression of CD24 is an independent prognostic factor for breast cancer.
      Recently, two polymorphisms in the CD24 gene were linked to disease risk and
      progression in autoimmune diseases. Here, we evaluated the clinical relevance of
      these polymorphisms with respect to their potential to predict a pathologic
      complete response (pCR) to neoadjuvant chemotherapy (NCT) for primary breast
      cancer (PBC), one of the strongest prognostic factors in this setting. A total of
      257 patients were randomized to either doxorubicin/cyclophosphamide (AC) or
      doxorubicin/pemetrexed (AP), both followed by docetaxel (Doc) as NCT for T2-4 N0
      2 M0 PBC as part of an international, multicenter, randomized phase II trial.
      CD24 polymorphisms were analyzed on germ line DNA and correlated with
      clinicopathologic variables and pCR. No significant associations were found
      between either of the polymorphisms and any of the clinicopathologic variables.
      In a multivariate analysis, CD24 Val/Val genotype was the only significant
      predictor of pCR (OR: 4.97; P = 0.003). The predictive potential was significant
      in both treatment arms and in the hormone receptor-positive subgroup. There was
      no correlation between CD24 3'UTR (TG/Del) genotype and pCR. We did not observe
      any association between CD24 genotype and CD24 protein expression or in vitro
      chemosensitivity, but there was a significant correlation between CD24 Val/Val
      and intratumoral lymphocyte aggregates. In conclusion, CD24 Ala/Val SNP is a
      strong and independent predictor of pCR after NCT for PBC and may affect immune
      functions rather than tumor characteristics. Further evaluation of the CD24
      function and validation of its predictive potential are clearly warranted.

PMID- 21960111
TI  - Is 18F-FDG PET accurate to predict neoadjuvant therapy response in breast cancer?
      A meta-analysis.
AB  - Clinical evidence regarding the value of (18)F-FDG PET for therapy responses
      assessment in breast cancer is increasing. The objective of this study is to
      evaluate the accuracy of (18)F-FDG PET in predicting responses to neoadjuvant
      therapies with meta-analysis and explore its optimal regimen for clinical use.
      Articles in English language relating to the accuracy of (18)F-FDG PET for this
      utility were retrieved. Methodological quality was assessed by QUADAS tool.
      Pooled estimation and subgroup analysis data were obtained by statistical
      analysis. Nineteen studies met the inclusion criteria and involved 920
      pathologically confirmed patients in total (mean age 49.8 years, all female).
      Methodological quality was relatively high. To predict histopathological response
      in primary breast lesions by PET, the pooled sensitivity, specificity, positive
      predictive value (PPV), negative predictive value (NPV), and diagnostic odds
      ratio were 84% (95% CI, 78-88%), 66% (95% CI, 62-70%), 50% (95% CI, 44-55%), 91%
      (95% CI, 87-94%), and 11.90 (95% CI, 6.33-22.36), respectively. In regional lymph
      nodes, sensitivity and NPV of PET were 92% (95% CI, 83-97%) and 88% (95% CI, 76
      95%), respectively. Subgroup analysis showed that performing a post-therapy (18)F
      FDG PET early (after the 1st or 2nd cycle of chemotherapy) was significantly
      better than later (accuracy 76% vs. 65%, P = 0.001). Furthermore, the best
      correlation with pathology was yielded by employing a reduction rate (RR) cutoff
      value of standardized uptake value between 55 and 65%. (18)F-FDG PET is useful to
      predict neoadjuvant therapy response in breast cancer. However, the relatively
      low specificity and PPV still call for caution. It is suggested to perform PET in
      an earlier course of therapy and use RR cutoff value between 55 and 65%, which
      might potentially identify non-responders early. However, further prospective
      studies are warranted to assess this regimen and adequately position PET in
      treatment management.

PMID- 21960112
TI  - A comparison of quality of life of early breast cancer patients treated with
      accelerated partial breast irradiation versus whole breast irradiation in China.
AB  - To compare quality of life (QoL) of early breast cancer patients treated with
      either accelerated partial breast irradiation (APBI) or whole breast irradiation
      (WBI) after breast-conserving therapy in China. The functional assessment of
      chronic illness therapy-Breast, traditional Chinese version 4 (FACT-B)
      instruments were given to 84 women (31 APBI and 53 WBI) who attended the
      radiotherapy clinic between July 2006 and May 2009 at Cancer Center of Sun Yat
      sen University. Baseline characteristics and Karnofsky performance status scores
      were not different between the two groups. The median follow-up period in the
      APBI group was 29 versus 34 months in the WBI group. The APBI group scores in the
      physical domain, functional domain, social domain, and breast-specific concerns
      of FACT-B were 23.01 +/- 3.91, 17.97 +/- 4.99, 20.87 +/- 4.80, and 22.55 +/-
      5.45, respectively, and were not significantly different from those of the WBI
      group (22.80 +/- 3.50, 17.50 +/- 4.40, 20.13 +/- 5.31, 23.81 +/- 4.65,
      respectively, P = 0.987, P = 0.476, P = 0.442, P = 0.330, respectively). However,
      the scores of the APBI group with respect to the emotional domains were lower
      compared to those of the WBI group (16.84 +/- 3.86 vs. 19.47 +/- 3.45,
      respectively, P = 0.002). Compared with women who underwent WBI, women treated
      with APBI were shown to have no significantly better QoL outcome, and yet had
      worse emotional response to their treatment.

PMID- 21960114
TI  - Excitonic properties of graphene-based materials.
AB  - First-principle density functional theory (DFT) calculations with quasiparticle
      corrections and many body effects are performed to study the electronic and
      optical properties of graphene-based materials. This review summarizes the
      excitonic properties including optical transition spectra and the distribution of
      exciton wavefunctions, thus providing the theoretical knowledge and predictions
      for promising optical applications of graphene materials.

PMID- 21960113
TI  - A randomized clinical trial comparing advanced pneumatic truncal, chest, and arm
      treatment to arm treatment only in self-care of arm lymphedema.
AB  - Treatment of the truncal lymphatics prior to treatment of the lymphedematous arm
      is an accepted, although not empirically tested, therapeutic intervention
      delivered during decongestive lymphatic therapy (DLT). Breast cancer survivors
      with arm lymphedema are encouraged to use these techniques when performing simple
      lymphatic drainage as part of their life-long lymphedema self-care. Self-massage
      is at times difficult and pneumatic compression devices are used by many patients
      to assist with self-care. One such device, the Flexitouch((r)) System, replicates
      the techniques used during DLT; however, the need for application of pneumatic
      compression in unaffected truncal areas to improve self-care outcomes in arm only
      lymphedema is not established. The objective of this study was to compare the
      therapeutic benefit of truncal/chest/arm advanced pneumatic compression therapy
      (experimental group) verses arm only pneumatic compression (control group) in
      self-care for arm lymphedema without truncal involvement using the
      Flexitouch((r)) System. Outcomes of interest were self-reported symptoms,
      function, arm impedance ratios, circumference, volume, and trunk circumference.
      Forty-two breast cancer survivors, (21 per group), with Stage II lymphedema
      completed 30 days of home self-care using the Flexitouch((r)) System. Findings
      revealed a statistically significant reduction in both the number of symptoms and
      overall symptom burden within each group; however, there were no statistically
      significant differences in these outcomes between the groups. There was no
      statistically significant overall change or differential pattern of change
      between the groups in function. A statistically significant reduction in
      bioelectrical impedance and arm circumference within both of the groups was
      achieved; however, there was no statistically significant difference in reduction
      between groups. These findings indicate that both configurations are effective,
      but that there may be no added benefit to advanced pneumatic treatment of the
      truncal lymphatics prior to arm massage when the trunk is not also affected.
      Further research is indicated in a larger sample.

PMID- 21960115
TI  - Dynamics of reactions between two closed-shell molecules.
AB  - The crossed molecular beam technique has been utilized to investigate a large
      number of elementary reactions. However, most of the studied reactions involve
      atoms or radicals; reactions between two stable molecular reactants are, in fact,
      seldom studied with the crossed molecular beam method. In this perspective,
      reactions between two stable molecules are reviewed and discussed. With crossed
      molecular beams and vacuum UV photoionization, the nascent products have been
      unambiguously identified. Consistent pictures of the reaction paths have been
      constructed based on the experimental data and ab initio calculations.
      Furthermore, there are intriguing features about the reaction barriers. The F(2)
      + organosulfur reactions are barrierless, demonstrating the first examples of
      such interactions between two closed-shell reactants. The barrier of F(2) +
      alkene reaction decreases with more methyl substitution groups at the C=C double
      bond, yet the absolute barrier heights from experiment and theory disagree with
      each other by ~2 kcal mol(-1), leaving an issue to be resolved in the future.

PMID- 21960116
TI  - Label-free supersandwich electrochemiluminescence assay for detection of sub
      nanomolar Hg2+.
AB  - A label-free supersandwich electrochemiluminescence assay based on T-Hg(2+)-T
      coordination and the intercalation of Ru(phen)(3)(2+) for Hg(2+) analysis was
      developed with excellent sensitivity and selectivity.

PMID- 21960117
TI  - Morphology, distribution, and evolution of apical structure of nematocysts in
      hexacorallia.
AB  - Cnidae are complex intracellular capsules made by all cnidarians. The most
      diverse of these capsules are nematocysts, which are made by all members of the
      phylum; spirocysts and ptychocysts are made only by members of some lineages, and
      they show less functional and structural diversity. In nematocysts, the apex has
      been shown to be either a hinged cap (operculum) or three flaps that flex outward
      during discharge. The operculum is known only from medusozoan nematocysts; flaps
      are known only from nematocysts of members of the hexacorallian order Actiniaria,
      although they have been inferred to be characteristic of Anthozoa, the group to
      which Actiniaria belongs. Using scanning and transmission electron microscopy, we
      discover a third apical morphology in nematocysts, an apical cap, which we find
      in all nonactiniarian anthozoans examined. This apical cap is identical
      structurally to the apical cap of spirocysts, and it resembles the apical
      structure of ptychocysts, whose apex is documented here for the first time.
      Additionally, a full survey of nematocysts from all body structures of two
      actiniarians demonstrates that a particular type of nematocyst, the microbasic p
      mastigophore of the mesenterial filaments, does not have apical flaps. The
      observed variation does not correspond to conventional categorization of capsule
      morphology and raises questions about the function and structure of capsules
      across Cnidaria. Despite some ambiguity in optimization of ancestral states
      across cnidae, we determine that the apical cap is the plesiomorphic structure
      for anthozoan cnidae and that apical flaps are a synapomorphy of Actiniaria. At
      present, the operculum is interpreted as a synapomorphy for Medusozoa, but either
      it or an apical cap is the ancestral state for nematocysts.

PMID- 21960118
TI  - Changes in PSA kinetics predict metastasis- free survival in men with PSA
      recurrent prostate cancer treated with nonhormonal agents: combined analysis of 4
      phase II trials.
AB  - BACKGROUND: Several phase II trials in men with noncastrate PSA-recurrent
      prostate cancer have assessed the impact of novel nonhormonal agents on PSA
      kinetics. However, it is unknown whether changes in PSA kinetics influence
      metastasis-free survival (MFS). METHODS: We performed a retrospective post hoc
      analysis of 146 men treated in 4 phase II trials examining the investigational
      agents marimastat (a matrix metalloproteinase inhibitor; n = 39), imatinib (a
      tyrosine kinase inhibitor; n = 25), ATN-224 (a copper/zinc-superoxide dismutase
      inhibitor; n = 22), and lenalidomide (an antiangiogenic/immunomodulatory drug; n
      = 60). We investigated factors influencing MFS, including within-subject changes
      in PSA kinetics (PSA slope, doubling time, and velocity) before and after
      treatment initiation. RESULTS: After a median follow-up of 16.8 months, 70
      patients (47.9%) developed metastases. In multivariable Cox regression models,
      factors that were independently predictive of MFS after adjusting for age and
      other clinical prognostic variables were baseline PSA doubling time (PSADT) (P =
      .05), baseline PSA slope (P = .01), on-study change in PSADT (P = .02), and on
      study change in PSA slope (P = .03). In a landmark Kaplan-Meier analysis, median
      MFS was 63.5 months (95% confidence interval [CI], 34.6-not reached) and 28.9
      months (95% CI, 13.5-68.0) for men with or without any decrease in PSA slope by 6
      months after treatment, respectively. CONCLUSIONS: This hypothesis generating
      analysis suggests that within-subject changes in PSADT and PSA slope after
      initiation of experimental therapy may correlate with MFS in men with
      biochemically recurrent prostate cancer. If validated in prospective trials,
      changes in PSA kinetics may represent a reasonable intermediate end point for
      screening new agents in these patients.

PMID- 21960119
TI  - Application of differential charging in XPS for structural study of Langmuir
      Blodgett films.
AB  - Differential charging in XPS was recently shown to be a novel technique for
      studying in-depth structural information of discrete cadmium layers in Langmuir
      Blodgett (LB) multilayer films. Here we report structural modification in
      multilayer LB films after sulfidation using differential charging in angle
      dependent XPS that are not observable by the x-ray reflectivity technique. An AFM
      study suggests less modification in compact LB films in comparison to the non
      compact ones. The differential charging in the LB multilayers changes after
      sulfidation due to the formation of cadmium sulfide nanostructures in the cadmium
      arachidate LB matrix, which was reflected prominently in the differential
      charging of Cd 3d(5/2) XPS peaks. It was found that, even after sulfidation, the
      compact multilayer LB films were differentially charged in the out-of-plane (in
      depth) direction, whereas this kind of differential charging was not apparent in
      rough and non-compact films. Our results clearly indicate that for LB films with
      compact structure a partial layered structure survives the impact of particle
      formation, whereas for non-compact films the modification is large and no
      specific conclusion could be drawn. While x-ray reflectivity cannot provide
      specific information about the internal structure of the post-sulfidation films
      it shows that the total thickness of the films reduces in all cases.

PMID- 21960120
TI  - Sensitivity of A-549 human lung cancer cells to nanoporous zinc oxide conjugated
      with Photofrin.
AB  - In the present study, we demonstrated the use of nanoporous zinc oxide (ZnO NPs)
      in photodynamic therapy. The ZnO NPs structure possesses a high surface to volume
      ratio due to its porosity and ZnO NPs can be used as an efficient photosensitizer
      carrier system. We were able to grow ZnO NPs on the tip of borosilicate glass
      capillaries (0.5 MUm diameter) and conjugated this with Photofrin for efficient
      intracellular drug delivery. The ZnO NPs on the capillary tip could be excited
      intracellularly with 240 nm UV light, and the resultant 625 nm red light emitted
      in the presence of Photofrin activated a chemical reaction that produced reactive
      oxygen species (ROS). The procedure was tested in A-549 cells and led to cell
      death within a few minutes. The morphological changes in necrosed cells were
      examined by microscopy. The viability of control and treated A-549 cells with the
      optimum dose of UV/visible light was assessed using the MTT assay, and ROS were
      detected using a fluorescence microscopy procedure.

PMID- 21960121
TI  - The role of vascular endothelial growth factor in fractional laser resurfacing
      with the carbon dioxide laser.
AB  - The aim of this study was to analyze the role of vascular endothelial growth
      factor (VEGF) in mechanisms of cutaneous remodeling induced by fractional CO(2)
      laser treatment. The dorsal skin of Kunming mice was exposed to a single-pass
      fractional CO(2) laser treatment. Biopsies were taken 1 h, and 1, 3, 7, 14, 28
      and 56 days after treatment. Skin samples VEGF expression was evaluated by
      immunohistochemistry and ELISA, fibroblasts by hematoxylin-eosin staining, and
      types I and III collagen by ELISA. Staining for VEGF was found in many types of
      cell including fibroblasts. The amount of VEGF in the skin of laser-treated areas
      had increased significantly compared to that in the control areas on days 1 and 3
      (P < 0.05, P < 0.01, respectively), then decreased by day 7 after treatment and
      returned to the baseline level. The number of fibroblasts in the skin of the
      laser-treated areas had increased significantly compared to that in control areas
      on days 3, 7, 14, 28 and 56 after irradiation (P < 0.05, P < 0.01, P < 0.01, P <
      0.01, P < 0.01, respectively). The amount of type I collagen was significantly
      higher in the skin of the laser-treated areas compared to that in control areas
      from day 28 to day 56 (P < 0.05, respectively), and type III collagen was
      significantly higher from day 3 to day 56 (P < 0.05, P < 0.05, P < 0.05, P <
      0.05, P < 0.01, respectively). There was a positive correlation between the level
      of VEGF and fibroblast proliferation early stage after laser treatment (r =
      0.853, P < 0.01), but there was no correlation after the first week (r = -0.124,
      P > 0.05). The amounts of type I and III collagen showed no significant
      correlations with the expression of VEGF in the late stages after laser treatment
      (r = 0.417, P > 0.05 and r = 0.340, P > 0.05, respectively). The results suggest
      that VEGF might be mainly involved in the early stages of wound healing,
      including the stages of acute inflammation, fibroblast proliferation and vessel
      formation induced by fractional CO(2) laser resurfacing.

PMID- 21960122
TI  - Lesion dimensions following ablative fractional laser treatment in non-melanoma
      skin cancer and premalignant lesions.

PMID- 21960123
TI  - Reduction of iron by decarboxylation in the formation of magnetite nanoparticles.
AB  - The process of formation of magnetite nanoparticles has been investigated by
      liquid chromatography and mass spectroscopy in the liquid phase decomposition of
      either Fe(III) acetylacetonate with decanoic acid or Fe(III) decanoate. In both
      cases, the dissociation into radicals of the iron carboxylate bonds provides the
      reduction of the Fe(III) cations and the oxygen atoms required for the formation
      of the mixed-valence inverse spinel magnetite structure. A reaction mechanism is
      proposed. It is also shown that the reaction of free decanoic acid with the
      Fe(III) cations in solution promotes the growth of faceted particles at the
      reflux temperature of the solvent (ca. 280  degrees C), while, under the same
      conditions, the stepwise decomposition of the Fe(III) decanoate generates smaller
      and pseudo-spherical particles. The latter also yields faceted particles when the
      temperature is increased above that of the total decomposition of the salt.
      Magnetic measurements make evident that the reaction starting from Fe(III)
      acetylacetonate yields nanoparticles with higher magnetization and lower spin
      disorder, due to the improved regularity of the surface crystal structure. The
      starting conditions for the decarboxylation process thus affect the morphology
      and magnetic properties of the resulting nanoparticles.

PMID- 21960124
TI  - Heat shock protein 70 inhibits hydrogen peroxide-induced nucleolar fragmentation
      via suppressing cleavage and down-regulation of nucleolin.
AB  - It has been reported that nucleolar fragmentation is a part of the overall
      apoptotic morphology, however, it is currently obscure whether and how nucleolar
      fragmentation can be induced by hydrogen peroxide (H(2)O(2)) and heat shock
      protein 70 (Hsp70) can prevent nucleolar fragmentation. To dissect these two
      questions, C(2)C(12) myogenic cells and immortalized mouse embryonic fibroblasts
      (MEFs) with heat shock transcriptional factor 1 (HSF1) null mutation were treated
      with heat shock response (HS) (42.5 +/- 0.5 degrees C for 1 h and recovery at 37
      degrees C for 24 h) and then were insulted with 0.5 mmol/L H(2)O(2).
      Morphological changes of nucleoli were observed under contrast microscope or
      electronic microscope. It was found that (1) stimulation with H(2)O(2)-induced
      nucleolar fragmentation by mediating cleavage and down-regulation of nucleolar
      protein, nucleolin in C(2)C(12) myocytes and MEFs; (2) HS suppressed nucleolar
      fragmentation by inducing the expression of Hsp70 in an HSF1-dependent manner as
      indicated by assays of transfection with Hsp70 antisense oligonucleotides (AS
      ONs) or recombinant plasmids of full-length Hsp70 cDNA; (3) protection of Hsp70
      against nucleolar fragmentation was related to its accumulation in nucleolus
      mediated by nuclear localization sequence and its inhibition against cleavage and
      down-regulation of nucleolin. These results suggested that H(2)O(2)-induced
      nucleolar fragmentation and HS or Hsp70 inhibit H(2)O(2)-induced nucleolar
      fragmentation through the translocation of Hsp70 into nucleolar and its
      protection against impairment of nucleolin.

PMID- 21960126
TI  - Improved procedural performance following a simulation training session may not
      be transferable to the clinical environment.
AB  - OBJECTIVE: Neonatal intubation is a life-saving procedural skill required by
      pediatricians. Trainees receive insufficient clinical exposure to develop this
      competency. Traditional training comprises a Neonatal Resuscitation Program (NRP)
      complemented by clinical experience. More recently, simulation is being used in
      procedural skills training. The objective of this study is to examine the impact
      of a simulation session, which teaches the skill of neonatal intubation by
      comparing pre- and post-intervention performance, and examining transferability
      of skill acquisition to the clinical setting. STUDY DESIGN: First-year pediatric
      residents with NRP training, but no previous neonatal experience, attended a 2-h
      intubation education session conducted by two experienced respiratory therapists.
      Individual components of the skill were taught, followed by practice on a high
      fidelity infant mannequin with concurrent feedback. Skills were assessed using a
      validated neonatal intubation checklist (CL) and a five-point global rating scale
      (GRS), pre- and immediately post-intervention, using the mannequin. Clinical
      intubations performed in the subsequent 8-week neonatal intensive-care unit
      (NICU) rotation were evaluated by documenting success rates, time taken to
      intubate, and CL and GRS scores. Performance was also compared with similar data
      collected on intubations performed by a historical cohort of first-year residents
      who did not receive the training intervention. Data were analyzed using
      descriptive statistics, Student's t-test and chi (2)-test as appropriate, and
      analysis of variance. RESULT: Thirteen residents participated in the educational
      session. Mean pre-intervention CL score was 65.4 +/- 18% (s.d.) and GRS was 3 +/-
      0.7 (s.d.). Performance improved following the intervention with post-training CL
      score of 93 +/- 5% (P<0.0001) and GRS of 3.92 +/- 0.4 (P=0.0003). These trainees
      performed 40 intubations during their subsequent NICU rotation, with a success
      rate of 67.5% compared with 63.15% in the cohort group (NS). However, mean CL
      score for the study trainees during the NICU rotation was 64.6 +/- 20%,
      significantly lower than their post-training CL score (P<0.001), and
      significantly lower than the historical cohort score of 82.5 +/- 15.4% (P=0.001).
      In the intervention group, there were no significant differences between the pre
      intervention and real-life CL scores of 65 +/- 18% and 64.63 %, respectively, and
      the pre-intervention and real-life GRS of 3.0 +/- 0.7 and 2.95 +/- 0.86,
      respectively. CONCLUSION: Trainees showed significant improvement in intubation
      skills immediately post intervention, but this did not translate into improved
      clinical performance, with performance returning to baseline. In fact,
      significantly higher CL scores were demonstrated by the cohort group. These data
      suggest that improved performance in the simulation environment may not be
      transferable to the clinical setting. They also support the evidence that
      although concurrent feedback may lead to improved performance immediately post
      training intervention, this does not result in improved skill retention overall.

PMID- 21960125
TI  - Genetic associations of surfactant protein D and angiotensin-converting enzyme
      with lung disease in preterm neonates.
AB  - OBJECTIVE: To replicate genetic associations with respiratory distress syndrome
      (RDS) and bronchopulmonary dysplasia (BPD) in genes related to surfactant
      deficiency, inflammation and infection, and the renin-angiotensin system. STUDY
      DESIGN: We examined eight candidate genes for associations with RDS and BPD in
      433 preterm birth (PTB-<37 weeks) infants (251 with RDS and 134 with BPD). Both
      case-control and family-based analyses were performed in preterm (<37 weeks) and
      very preterm birth (VPTB-<32 weeks) infants. RESULT: We replicated a previous
      finding that rs1923537, a marker downstream of surfactant protein D (SFTPD) is
      associated with RDS in VPTB infants in that the T allele was overtransmitted from
      parents to offspring with RDS (P=8.4 * 10(-3)). We also observed the A allele of
      rs4351 in the angiotensin-converting enzyme (ACE) gene was overtransmitted from
      parents to VPTB offspring with BPD (P=9.8 * 10(-3)). CONCLUSION: These results
      give further insight into the genetic risk factors for complex neonatal
      respiratory diseases and provide more evidence of the importance of SFTPD and ACE
      in the etiology of RDS and BPD, respectively.

PMID- 21960127
TI  - Evaluation of human milk fortification from the time of the first feeding:
      effects on infants of less than 31 weeks gestational age.
AB  - OBJECTIVE: To determine whether human milk fortification from the time of the
      first feeding significantly improves weight gain and bone mineral status in
      infants of <31 weeks estimated gestational age as compared with delayed or
      standard human milk fortification. STUDY DESIGN: This was a retrospective pre
      post design. In all, 95 infants born at <31 weeks estimated gestational age were
      compared. There were 53 infants in the early fortification group (EFG) and 42
      infants in the delayed fortification group (DFG). They were compared with regard
      to weight gain at 34 weeks postmenstrual age (PMA), and their serum levels of
      calcium, phosphorus and alkaline phosphatase levels were compared as an indicator
      of bone mineral status. The practice change of fortifying all human milk given to
      preterm infants at <34 weeks PMA commenced in June 2009. The usual practice of
      fortification took place once an infant had reached a feeding volume of 50 to 100
      ml kg(-1) per day. The new practice fortified all human milk with a powdered
      human milk fortifier to 24 calories per ounce, starting with the first feeding,
      no matter how small the volume. RESULT: There were no differences in weight gain
      between the EFG and the DFG. The group that received fortification from the time
      of the first feeding were significantly less likely to have alkaline phosphatase
      levels >500 U l(-1) from 33 weeks PMA onward. There was no incidence of feeding
      intolerance with early fortification. CONCLUSION: Fortification of human milk
      from the time of the first feeding does not affect weight gain at 34 weeks PMA,
      but is related to a lower incidence of elevated alkaline phosphate levels and
      does not cause feeding intolerance.

PMID- 21960128
TI  - Differences in thermal adaptation of infants delivered at primary or tertiary
      care facilities in India.
AB  - OBJECTIVE: To compare the pattern of thermal stabilization seen in infants born
      at a rural primary health center (PHC) with that of infants born in an modern
      urban tertiary care hospital (TCH). STUDY DESIGN: Abdominal temperature (Ta) and
      foot temperature (Tf) of healthy term newborn infants were monitored and
      electronically recorded continuously from birth in the delivery room (DR) until
      12 h of life in the postnatal ward (PNW) at two sites. A total of 71 infants were
      enrolled in the study: 51 infants at the PHC and 20 infants at the TCH. RESULT:
      In infants delivered at TCH the maximum mean (+/-s.d.) Ta of 36.4  degrees  C +/-
      0.48 was reached by 12 h, while at PHC maximum mean Ta was 35.4  degrees C (1.98)
      by 10.5 h. The mean Tf improved from the lowest value of 29.7  degrees C +/- 1.3
      at 4.5 h to 32.9  degrees C+/-1.6 by 12 h of life in infants delivered at TCH,
      whereas in infants delivered at PHC Tf remained low (maximum 30.7  degrees C) all
      through 12 h. The mean Td (Ta-Tf) gradually decreased from a maximum of 5.9 
      degrees C +/- 1.6 at 4.5 h to 3.5  degrees C +/- 1.5 by 12 h of life in infants
      born at TCH, but the Td remained at >5  degrees C even after 6 h of life in
      infants born at PHC, which was statistically significant (P<0.05). The calculated
      area between the Ta and Tf, a proxy for metabolic stress was greater in babies
      born at PHC than those born at TCH. CONCLUSION: Our study shows that although
      both groups of newborn infants experienced significant thermal stress, infants
      delivered at PHC experienced significantly greater thermal stress than babies
      born at TCH. This difference could be attributed to the differences in thermal
      environment of DR and PNW between PHC and TCH.

PMID- 21960129
TI  - Hypoproteinemia on the first day of life and adverse outcome in very preterm
      infants admitted to the neonatal intensive care unit.
AB  - OBJECTIVE: We aimed to investigate the relationship between day-1 hypoproteinemia
      and severe adverse outcome (SAO) in very preterm infants admitted to the neonatal
      intensive care unit (NICU). STUDY DESIGN: Retrospective study of all patients
      born from 24 to 31 weeks gestation and cared for in our NICU over an 8-year
      period. Infants were excluded if the serum protein value on the first day of life
      was not available. RESULT: A total of 913 patients were included. In all, 14.6%
      presented with SAO (death or severe neurological injury on cranial ultrasound).
      Hypoproteinemia (total protein level <40 g l(-1)) on day 1 of life occurred in
      19.5 % of all patients. The rate of SAO was 33.7% in patients with
      hypoproteinemia and 9.9% in those with normoproteinemia (P<0.0001). Logistic and
      multiple regression analysis confirmed that the association hypoproteinemia-SAO
      remained significant after adjustment for the other major predictors of outcome
      present at baseline (odds ratio 3.4; 95% confidence interval 2.1-5.4; P<0.0001).
      CONCLUSION: Hypoproteinemia was highly associated with SAO in this cohort of
      critically ill preterm infants. We are unable to explain the link between
      hypoproteinemia and adverse outcome in our population. This investigation serves
      as a hypothesis-generating report of a large preterm infants sample, and suggests
      the need to assess the predictive accuracy for adverse outcome of hypoproteinemia
      in future prospective studies.

PMID- 21960130
TI  - Altered transitional circulation in infants of diabetic mothers with strict
      antenatal obstetric management: a functional echocardiography study.
AB  - OBJECTIVE: Infants born to diabetic mothers (IDMs) even with good glycemic
      control are at risk for neonatal morbidity. Many of these problems occur during
      neonatal transition. We assessed (i) systemic and pulmonary blood flow in IDMs
      compared with controls and (ii) directional blood flow changes within fetal
      shunts during the first few days of life. STUDY DESIGN: In this prospective
      observational cohort study, we evaluated right (RVO) and left ventricular output,
      superior vena cava flow, atrial and ductal shunts, and tricuspid regurgitation in
      32 IDMs and 18 controls using serial echocardiography after birth and 48 h of
      life in both groups and at 24 and 72 h in IDMs only. RESULT: IDMs had lower RVO
      after birth and 48 h of life. IDMs also had less left to right atrial shunt and
      more right to left ductal shunt after birth compared with controls. In all, 15 of
      the 32 IDMs were admitted to the neonatal intensive care unit and 11 had
      respiratory symptoms. CONCLUSION: Persistence of fetal shunts and decreased RVO
      in IDMs suggest that even those with good gestational control have impaired
      transitional hemodynamics.

PMID- 21960131
TI  - A hybrid method of application of independent component analysis to in vivo 1H MR
      spectra of childhood brain tumours.
AB  - Independent component analysis (ICA) can automatically extract individual
      metabolite, macromolecular and lipid (MMLip) components from a series of in vivo
      MR spectra. The traditional feature extraction (FE)-based ICA approach is
      limited, in that a large sample size is required and a combination of metabolite
      and MMLip components can appear in the same independent component. The
      alternative ICA approach, based on blind source separation (BSS), is weak when
      dealing with overlapping peaks. Combining the advantages of both BSS and FE
      methods may lead to better results. Thus, we propose an ICA approach involving a
      hybrid of the BSS and FE techniques for the automated decomposition of a series
      of MR spectra. Experiments were performed on synthesised and patient in vivo
      childhood brain tumour MR spectra datasets. The hybrid ICA method showed an
      improvement in the decomposition ability compared with BSS-ICA or FE-ICA, with an
      increased correlation between the independent components and simulated metabolite
      and MMLip signals. Furthermore, we were able to automatically extract metabolites
      from the patient MR spectra dataset that were not in commonly used basis sets
      (e.g. guanidinoacetate).

PMID- 21960132
TI  - Severity of doxorubicin-induced small intestinal mucositis is regulated by the
      TLR-2 and TLR-9 pathways.
AB  - Intestinal mucositis is a serious complication of cancer chemotherapy and
      radiotherapy; it frequently compromises treatment and dramatically reduces the
      quality of life of patients. Different approaches to limit the damage to the
      intestine during anti-cancer therapy have been largely ineffective due to
      insufficient knowledge of the mechanism of mucositis development. This study
      aimed to define the role of TLR-2 and TLR-9 in the modulation of small intestinal
      damage in a model of doxorubicin-induced mucositis. Doxorubicin-induced
      intestinal damage was verified by a histological score (HS), analysis of
      leukocyte influx into the lamina propria, and determination of the number of
      apoptotic cells. Additionally, the activation status of glycogen synthase kinase
      3beta (GSK-3beta) was assessed. Wild-type (WT) mice injected with doxorubicin
      demonstrated severe intestinal damage (HS 8.0 +/- 0.81), reduction of villus
      length to 43.9% +/- 13.7% of original length, and increased influx of leukocytes
      as compared to vehicle-injected mice (HS 1.33 +/- 1.15). The protective effect of
      TLR-2 or TLR-9 deficiency was associated with a significant decrease of the HS as
      compared to WT mice. In the ileum, a minor reduction of villus length and a
      decreased number of infiltrating leukocytes and TUNEL-positive cells was
      observed. We demonstrate that the TLR-9 antagonist ODN2088 reduces doxorubicin
      induced intestinal damage. Furthermore, we show that GSK-3beta activity is
      inhibited in the absence of TLR-2. The protective capacity of GSK-3beta
      suppression was observed in WT mice by inhibiting it with the specific inhibitor
      SB216763. Overall, our findings demonstrate that the TLR-2/GSK-3beta and TLR-9
      signalling pathways play a central role in the development of intestinal
      mucositis and we suggest a new therapeutic strategy for limiting doxorubicin
      induced intestinal inflammation.

PMID- 21960133
TI  - Diffusion tensor imaging in carpal tunnel syndrome.
AB  - PURPOSE: We aimed to investigate the efficacy of diffusion tensor imaging in the
      diagnosis of carpal tunnel syndrome and to obtain a quantitative parameter that
      may contribute to the diagnosis. MATERIALS AND METHODS: The median nerves in 57
      wrists of 38 patients diagnosed as carpal tunnel syndrome and 30 wrists of 24
      normal subjects were prospectively evaluated with a 3T Philips scanner, using
      standard 8-channel SENSE head coil. Diffusion tensor imaging was performed using
      spin echo-echo planar imaging. For anatomical reference, a T1-weighted sequence
      was acquired. Fractional anisotropy and apparent diffusion coefficient
      measurements were done focally at the carpal tunnel level and from whole median
      nerve. RESULTS: In carpal tunnel syndrome patients, both focal carpal tunnel and
      whole nerve measurements demonstrated statistically significantly lower
      fractional anisotropy values than normal subjects (P < 0.001). No statistically
      significant difference was observed in apparent diffusion coefficient
      measurements. The cut-off value obtained by receiver operator characteristics
      analysis was 0.554 for focal carpal tunnel fractional anisotropy (sensitivity,
      80%; specificity, 80%) and 0.660 for whole nerve fractional anisotropy
      (sensitivity, 82%; specificity, 80%) measurement. CONCLUSION: Diffusion tensor
      imaging may contribute to the diagnosis of carpal tunnel syndrome on the basis of
      fractional anisotropy measurements.

PMID- 21960134
TI  - HASTE diffusion-weighted MRI for the reliable detection of cholesteatoma.
AB  - PURPOSE: To assess the detection efficiency of Half-Fourier acquisition single
      shot turbo spin-echo (HASTE) diffusion-weighted magnetic resonance imaging (MRI)
      for cholesteatoma. MATERIALS AND METHODS: A total of 21 patients with suspected
      primary (n=16) or recurrent cholesteatoma (n=5) underwent MRI in a 1.5 Tesla
      scanner using an adapted protocol for cholesteatoma detection that included a
      coronal HASTE diffusion-weighted MRI sequence. The cholesteatoma diagnosis was
      based on evidence of a hyperintense lesion at b-1000 on diffusion-weighted
      images. The imaging findings were correlated with findings from surgery or
      clinical evaluations in all patients. RESULTS: HASTE diffusion-weighted MRI
      successfully detected 11 primary and 5 recurrent lesions out of 17 cholesteatomas
      (sensitivity, 94.1%). One primary cholesteatoma with a diameter of 4-5 mm was
      missed. MRI of patients without cholesteatoma were correctly interpreted as
      negative for cholesteatoma (specificity, 100%). The positive and negative
      predictive values for the HASTE diffusion-weighted MRI in detecting cholesteatoma
      were 100% and 80%, respectively. CONCLUSION: HASTE diffusion-weighted MRI offers
      great promise for cholesteatoma screening. The addition of this sequence to the
      posterior fossa MRI protocol may preclude unnecessary cholesteatoma surgery.

PMID- 21960135
TI  - Incidental findings in the maxillofacial region detected by cone beam CT.
AB  - PURPOSE: The purpose of this study was to determine the location, nature, and
      occurrence of incidental maxillofacial findings on cone beam computed tomography
      (CBCT) scans performed for maxillofacial diagnostic purposes. MATERIALS AND
      METHODS: CBCT images of 207 consecutive patients (129 females and 78 males) were
      examined. The sample consisted of 85 temporomandibular joint (TMJ) disorder
      patients, 45 paranasal sinusitis patients, 30 obstructive sleep apnea syndrome
      patients, 15 implant patients, and 32 others. RESULTS: The overall rate of
      incidental findings was 92.8%. The highest rate of incidental findings was in the
      airway area (51.8%), followed by impacted teeth (21.7%), TMJ findings (11.1%),
      endodontic lesions (4.3%), condensing osteitis (1%), and others (2.9%). The
      airway incidental findings included mucosal thickening (21.3%), deviation of the
      nasal septum (12.6%), conchal hypertrophy (11.1%), bullous concha (3.9%), and
      retention cysts (2.9%). The impacted teeth consisted of third molars (18.8%) and
      canines (2.9%). The incidental findings for the TMJ patients were erosion of the
      condyle (4.8%), osteophytes (3.4%), and bifid condyle (2.9%). CONCLUSION: Oral
      radiologists should be aware of possible incidental findings and should be
      vigilant about comprehensively evaluating possible underlying diseases.

PMID- 21960136
TI  - The anatomic evaluation of the internal mammary artery using multidetector CT
      angiography.
AB  - PURPOSE: To determine the normal anatomic features and variations of the internal
      mammary arteries (IMAs) and to describe the relationship between the diameter and
      distance to the sternal edge of the IMAs, gender, and location (right-left) of
      the IMAs in patients who underwent multidetector computed tomography (MDCT)
      angiography of the thorax for various reasons. MATERIALS AND METHODS: A total of
      164 patients who underwent MDCT angiography of the thoracic vascular structures
      for various reasons were analyzed retrospectively. The right and left IMAs were
      analyzed individually, and normal anatomic features and variations were recorded.
      The relationships between gender, side and diameter of the IMAs, and distance to
      the sternal edge of the IMAs were evaluated. RESULTS: There were 328 (164 right,
      164 left) IMAs in 164 patients (110 males, 54 females; mean age, 43.96 years). A
      total number of five arteries (1.5%) had anatomic variation. Whereas 325 IMAs had
      an origin separate from the subclavian artery, three LIMA of the 328 arteries
      (0.91%) had a common origin with the thyrocervical trunk or costocervical trunk.
      Two (0.6%) IMAs (one LIMA and one RIMA) in the same patient were duplicated at
      the level of the first and second costal cartilage. There were no statistically
      significant correlations between age and diameter or between gender and diameter
      of the RIMA and LIMA at the origin and level of tracheal bifurcation (P > 0.05).
      Mean distance between the lateral margin of the sternum and midpoint of LIMA and
      RIMA were 12.42 mm and 13.00 mm, respectively. CONCLUSION: The normal anatomic
      features and variations of the IMAs have an important role in cardiovascular
      bypass surgery, breast reconstruction, and percutaneous transthoracic procedures.
      MDCT angiography allows a precise and detailed evaluation of IMAs.

PMID- 21960137
TI  - Perioperative infliximab application has marginal effects on ischemia-reperfusion
      injury in experimental small bowel transplantation in rats.
AB  - PURPOSE: Ischemia-reperfusion injury leads to impaired smooth muscle function and
      inflammatory reactions after intestinal transplantation. In previous studies,
      infliximab has been shown to effectively protect allogenic intestinal grafts in
      the early phase after transplantation with resulting improved contractility. This
      study was designed to reveal protective effects of infliximab on ischemia
      reperfusion injury in isogenic transplantation. METHODS: Isogenic, orthotopic
      small bowel transplantation was performed in Lewis rats (3 h cold ischemia). Five
      groups were defined: non-transplanted animals with no treatment (group 1),
      isogenic transplanted animals with vehicle treatment (groups 2/3) or with
      infliximab treatment (5 mg/kg body weight intravenously, directly after
      reperfusion; groups 4/5). The treated animals were sacrificed after 3 (group 2/4)
      or 24 h (group 3/5). Histological and immunohistochemical analysis, TUNEL
      staining, real-time RT-PCR, and contractility measurements in a standard organ
      bath were used for determination of ischemia-reperfusion injury. RESULTS: All
      transplanted animals showed reduced smooth muscle function, while no significant
      advantage of infliximab treatment was observed. Reduced infiltration of
      neutrophils was noted in the early phase in animals treated with infliximab. The
      structural integrity of the bowel and infiltration of ED1-positive monocytes and
      macrophages did not improve with infliximab treatment. At 3 h after reperfusion,
      mRNA expression of interleukin (IL)-6, TNF-alpha, IL-10, and iNOS and MCP-1
      displayed increased activation in the infliximab group. CONCLUSION: The
      protective effects of infliximab in the early phase after experimental small
      bowel transplantation seem to be unrelated to ischemia-reperfusion injury. The
      promising effects in allogenic transplantation indicate the need for further
      experiments with infliximab as complementary treatment under standard
      immunosuppressive therapy. Further experiments should focus on additional
      infliximab treatment in the setting of acute rejection.

PMID- 21960138
TI  - The ROXY1 C-terminal L**LL motif is essential for the interaction with TGA
      transcription factors.
AB  - Glutaredoxins (GRXs) are small, ubiquitous, glutathione-dependent oxidoreductases
      that participate in redox-regulated processes associated with stress responses.
      Recently, GRXs have been shown to exert crucial functions during flower
      developmental processes. GRXs modulate their target protein activities by the
      reduction of protein disulfide bonds or deglutathionylation reactions. The
      Arabidopsis (Arabidopsis thaliana) GRX ROXY1 participates in petal primordia
      initiation and further petal morphogenesis. ROXY1 belongs to a land plant
      specific class of GRXs with a CC-type active site motif, deviating from the
      ubiquitously occurring CPYC and CGFS GRX classes. ROXY1 was previously shown to
      interact with floral TGA transcription factors in the nucleus, and this
      interaction is a prerequisite for ROXY1 to exert its activity required for
      Arabidopsis petal development. Deletion analysis further identified the
      importance of the ROXY1 C terminus for the ROXY1/TGA protein interactions and for
      the ROXY1 function in petal development. Here, by dissecting the ROXY1 C
      terminus, an alpha-helical L**LL motif immediately adjacent to the ROXY1 C
      terminal eight amino acids was identified that is essential for the interaction
      with TGA transcription factors and crucial for the ROXY1 function in planta.
      Similar to the alpha-helical L**LL motifs binding to transcriptional coactivators
      with liganded nuclear receptors in animals, a hydrophobic face formed by the
      conserved leucines in the L**LL motif of ROXY1 possibly mediates the interaction
      with TGA transcription factors. Thus, the alpha-helical L**LL sequence is a
      conserved protein-protein interaction motif in both animals and plants.
      Furthermore, two separate TGA domains were identified by deletion experiments as
      being essential for mediating TGA protein interactions with ROXYs.

PMID- 21960139
TI  - The sink-specific plastidic phosphate transporter PHT4;2 influences starch
      accumulation and leaf size in Arabidopsis.
AB  - Nonphotosynthetic plastids are important sites for the biosynthesis of starch,
      fatty acids, and amino acids. The uptake and subsequent use of cytosolic ATP to
      fuel these and other anabolic processes would lead to the accumulation of
      inorganic phosphate (Pi) if not balanced by a Pi export activity. However, the
      identity of the transporter(s) responsible for Pi export is unclear. The plastid
      localized Pi transporter PHT4;2 of Arabidopsis (Arabidopsis thaliana) is
      expressed in multiple sink organs but is nearly restricted to roots during
      vegetative growth. We identified and used pht4;2 null mutants to confirm that
      PHT4;2 contributes to Pi transport in isolated root plastids. Starch accumulation
      was limited in pht4;2 roots, which is consistent with the inhibition of starch
      synthesis by excess Pi as a result of a defect in Pi export. Reduced starch
      accumulation in leaves and altered expression patterns for starch synthesis genes
      and other plastid transporter genes suggest metabolic adaptation to the defect in
      roots. Moreover, pht4;2 rosettes, but not roots, were significantly larger than
      those of the wild type, with 40% greater leaf area and twice the biomass when
      plants were grown with a short (8-h) photoperiod. Increased cell proliferation
      accounted for the larger leaf size and biomass, as no changes were detected in
      mature cell size, specific leaf area, or relative photosynthetic electron
      transport activity. These data suggest novel signaling between roots and leaves
      that contributes to the regulation of leaf size.

PMID- 21960140
TI  - Relationship of human paraoxonase-1 serum activity and genotype with
      atherosclerosis in individuals from the Deep South.
AB  - OBJECTIVE: Paraoxonase-1 (PON1) is synthesized in the liver and is bound to high
      density lipoprotein particles in blood. PON1 protects against the development of
      atherosclerosis by metabolizing proatherogenic-oxidized lipids. The Southeastern
      USA (excluding Florida) has the country's highest age-adjusted mortality rate of
      cardiovascular disease. This study determines the association of PON1 status with
      atherosclerosis in individuals from the Southeastern USA. METHODS: Eighty African
      Americans (40 men, 40 women) and 120 Caucasians (60 men, 60 women) were enrolled
      from a cardiology practice in Northeastern Mississippi. Serum PON1 activities
      were determined using diazoxon, paraoxon, and phenyl acetate (PhAc) as
      substrates. The PON1(192) genotype of each individual was also determined. A
      multivariable logistic regression model was developed to identify the
      associations of clinical characteristics, serum PON1 activity, and PON1(192)
      genotype of the study population with atherosclerosis. RESULTS: A core model
      consisting of age, sex, history of smoking, hypertension, and low-density
      lipoprotein-cholesterol group was constructed. The maximum-rescaled generalized
      r(2) value for the core model was 0.35. Addition of PON1 activity assessed by
      PhAc hydrolysis was the only measure of PON1 enzymatic activity to add
      significant information to the core model (P=0.0317) with the maximum-rescaled
      generalized r(2) value increasing to 0.37. Increasing PON1 activity was
      associated with decreased odds of atherosclerosis. The PON1(192) genotype was not
      significantly associated with atherosclerosis. CONCLUSION: Increasing PON1
      activity assessed by the hydrolysis of PhAc is associated with decreased odds of
      atherosclerosis in a group of African American and Caucasian Southerners.

PMID- 21960141
TI  - 4-Methylsulfanyl-3-butenyl isothiocyanate derived from glucoraphasatin is a
      potent inducer of rat hepatic phase II enzymes and a potential chemopreventive
      agent.
AB  - The objective of this study was to establish whether the phytochemical
      glucoraphasatin, a glucosinolate present in cruciferous vegetables, and its
      corresponding isothiocyanate, 4-methylsulfanyl-3-butenyl isothiocyanate, up
      regulate enzymes involved in the detoxification of carcinogens and are thus
      potential chemopreventive agents. Glucoraphasatin and myrosinase were isolated
      and purified from Daikon sprouts and Sinapis alba L., respectively.
      Glucoraphasatin (0-10 MUM) was incubated for 24 h with precision-cut rat liver
      slices in the presence and absence of myrosinase, the enzyme that converts the
      glucosinolate to the isothiocyanate. The intact glucosinolate failed to influence
      the O-dealkylations of methoxy- and ethoxyresorufin or the apoprotein expression
      of CYP1 enzymes. Supplementation with myrosinase led to an increase in the
      dealkylation of methoxyresorufin, but only at the highest concentration of the
      glucosinolate, and CYP1A2 expression. In the absence of myrosinase,
      glucoraphasatin caused a marked increase in epoxide hydrolase activity at
      concentrations as low as 1 MUM paralleled by a rise in the enzyme protein
      expression; at the highest concentration only, a rise was also observed in
      glucuronosyl transferase activity, but other phase II enzyme systems were
      unaffected. Addition of myrosinase to the glucoraphasatin incubation maintained
      the rise in epoxide hydrolase and glucuronosyl transferase activities, further
      elevated quinone reductase and glutathione S-transferase activities, and
      increased total glutathione concentrations. It is concluded that at low
      concentrations, glucoraphasatin, either intact and/or through the formation of 4
      methylsulfanyl-3-butenyl isothiocyanate, is a potent inducer of hepatic enzymes
      involved in the detoxification of chemical carcinogens and merits further
      investigation for chemopreventive activity.

PMID- 21960142
TI  - Silicon nanowire arrays-induced graphene oxide reduction under UV irradiation.
AB  - This paper reports on efficient UV irradiation-induced reduction of exfoliated
      graphene oxide. Direct illumination of an aqueous solution of graphene oxide at
      lambda = 312 nm for 6 h resulted in the formation of graphene nanosheets
      dispersible in water. X-Ray photoelectron spectroscopy (XPS), UV-vis
      spectroscopy, atomic force microscopy (AFM) and electrochemical measurements
      (cyclic voltammetry and electrochemical impedance spectroscopy) suggest a
      restoration of the sp(2) carbon network. The results were compared with graphene
      nanosheets prepared by photochemical irradiation of a GO aqueous solution in the
      presence of hydrogenated silicon nanowire (SiNW) arrays or silicon nanowire
      arrays decorated with silver (SiNW/Ag NPs) or copper nanoparticles (SiNW/Cu NPs).
      Graphene nanosheets obtained by illumination of the GO aqueous solution at 312 nm
      for 6 h in the presence of SiNW/Cu NPs exhibited superior electrochemical charge
      transfer characteristics. This is mainly due to the higher amount of sp(2)
      hybridized carbon in these graphene sheets found by XPS analysis. The high level
      of extended conjugated carbon network was also evident by the water insoluble
      nature of the resulting graphene nanosheets, which precipitated upon
      photochemical reduction.

PMID- 21960143
TI  - Depletion of cathepsin D by transglutaminase 2 through protein cross-linking
      promotes cell survival.
AB  - Transglutaminase 2 (TGase 2) promotes nuclear factor-kappaB (NF-kappaB) activity
      through depletion of the inhibitory subunit of NF-kappaB (I-kappaBalpha) via
      protein cross-linking, leading to resolution of inflammation. Increased
      expression of TGase 2 contributes to inflammatory disease pathogenesis via
      constitutive NF-kappaB activation. Conversely, TGase 2 inhibition often reverses
      inflammation in animal models. The role of TGase 2 in apoptosis remains less
      clear, as both pro- and anti-apoptotic functions of TGase 2 have been
      demonstrated under different experimental conditions. Apoptosis is intact in a
      TGase 2 knock out mouse (TGase2(-/-)), which is phenotypically normal. However,
      upon exposure to tumor necrosis factor (TNF)-alpha-induced apoptotic stress,
      mouse embryonic fibroblasts (MEFs) from TGase2(-/-) mice were more sensitive to
      cell death than MEFs from wild-type (TGase 2(+/+)) mice. In the current study, to
      explore the role of TGase 2 in apoptosis, TGase 2-binding proteins were
      identified by LC/MS. TGase 2 was found to associate with cathepsin D (CTSD).
      Binding of TGase 2 to CTSD resulted in the depletion of CTSD via cross-linking in
      vitro as well as in MEFs, leading to decreased levels of apoptosis. Furthermore,
      cytoplasmic CTSD levels were higher in MEFs from TGase 2(-/-) mice than in those
      from TGase 2(+/+) mice, as were caspase 3 activation and poly (ADP-ribose)
      polymerase (PARP) processes. These results suggest that TGase 2, while not
      previously implicated as a major regulatory factor in apoptosis, may regulate the
      balance between cell survival and cell death through the modulation of CTSD
      levels.

PMID- 21960144
TI  - Quo vadis, agostic bonding?
AB  - The role of agostic bonds in chemistry is highlighted. In particular, attention
      is given to the origin of the term, methods of investigations and their function
      in chemistry.

PMID- 21960145
TI  - Occupational exposure to metal compounds and lung cancer. Results from a multi
      center case-control study in Central/Eastern Europe and UK.
AB  - PURPOSE: To study the association between occupational exposure to metals
      including chromium, cadmium, nickel, and arsenic compounds, within a population
      based study design, while adjusting for confounding factors. METHODS: A
      population-based lung cancer case-control study in Central/Eastern Europe and UK
      was conducted in 1998-2003, including 2,853 cases and 3,104 controls. Exposure to
      70 occupational agents was assessed by local expert-teams for all subjects. Odds
      ratios (OR) for exposure to dust and fumes/mist of chromium, nickel, cadmium,
      arsenic, as well as inorganic pigment dust and inorganic acid mist, were
      adjusting for smoking, age, center, sex, and exposure to other occupational
      agents including the metals under study. RESULTS: Exposure to arsenic (prevalence
      = 1.4%) was associated with an increased lung cancer risk ((OR) 1.65, 95%
      confidence interval (95% CI):1.05-2.58). For chromium dust (prevalence = 4.8%,
      OR: 1.25, 95% CI: 0.95-1.65), a linear upward trend for duration and cumulative
      exposure was observed. A weak association was observed for exposure to cadmium
      fumes (prevalence = 1.8%, OR: 1.19, 95% CI: 0.77-1.82), which was strongest for
      the highest category of cumulative exposure (OR: 2.04, 95% CI: 1.07-3.90). No
      increased risk was observed for inorganic acid mist, inorganic pigment dust, or
      nickel, after adjustment for other metals. An independent effect of nickel cannot
      be excluded, due to its collinearity with chromium exposure. CONCLUSIONS:
      Occupational exposure to metals is an important risk factor for lung cancer.
      Although the strongest risk was observed for arsenic, exposure to chromium dust
      was most important in terms of attributable risk due to its high prevalence.

PMID- 21960146
TI  - Body mass index, long-term weight change, and esophageal squamous cell carcinoma:
      is the inverse association modified by smoking status?
AB  - BACKGROUND: Observational studies suggest that body mass index (BMI) is inversely
      associated with esophageal squamous cell carcinoma (ESCC). However, questions
      remain regarding reverse causation and confounding, especially by smoking, as
      alternative explanations. METHODS: The authors examined the association between
      BMI and measures of weight history and risk of ESCC in a population-based
      Australian case-control study (from 2002 to 2005) comprising 287 patients with
      ESCC (cases) and a control group of 1544 individuals who were sampled from a
      population registry. Stratified analyses were performed specifically to explore
      whether this association was influenced by smoking. Multivariable logistic
      regression models were used to derive odds ratios (ORs). RESULTS: After adjusting
      for smoking, significant inverse associations with ESCC for BMI and weight 1 year
      before diagnosis, maximum adult BMI, and weight gain since age 20 years were
      observed (all P(trend) < .001). The risk of ESCC was reduced by 35% (range, 23%
      44%) per 5-unit increase in recent BMI. Participants who gained weight after age
      20 years had a lower risk than those who maintained their weight during adult
      life (OR for gain of >20 kg, 0.51; 95% confidence interval [CI], 0.33-0.77). In
      stratified analyses, higher BMI was associated with a decreasing risk of ESCC
      both in never-smokers (OR, 0.32; 95% CI 0.13-0.76) and smokers (OR 0.22, 95%CI
      0.07-0.67) comparing the highest versus the lowest BMI quintile. CONCLUSIONS: In
      this study, the inverse associations between BMI, long-term weight gain, and
      other body measures and ESCC appeared to be robust and could not be explained by
      smoking status or potential confounding factors.

PMID- 21960147
TI  - Pilot study to evaluate ecological momentary assessment of tinnitus.
AB  - OBJECTIVES: Because audiometric evaluation, symptom histories, questionnaires,
      and similar standard assessment tools may not adequately sample the effects of
      chronic tinnitus on day-to-day activities, there is a need for alternative
      methodological approaches to study the impact of tinnitus on day-to-day life. An
      innovative methodological approach that has shown great promise in the study of
      chronic health problems characterized by reported temporal and/or situational
      variability in symptoms and distress is known as ecological momentary assessment
      (EMA). EMA involves the real-time measurement of states, situational factors, and
      symptoms by individuals as they go about their day-to-day activities. The
      objective of this pilot investigation was to explore the feasibility of using EMA
      methods to examine within- and between-day effects of tinnitus. DESIGN: This
      study was conducted in three phases: (1) design and development of an EMA
      methodology that could be used to assess effects of tinnitus; (2) refinement of
      the methodology through the use of two focus groups; and (3) field-test the
      methodology with individuals who experienced bothersome tinnitus. For Phase 3,
      each of the 24 participants wore, throughout their waking hours for 2 weeks, a
      personal digital assistant that produced alerts four times a day. The alerts
      prompted participants to respond to 19 questions, including 9 relating to
      situational and mood factors and 10 comprising the Tinnitus Handicap Inventory
      Screening version (THI-S). To evaluate for potential reactive effects of
      performing the EMA protocol, each participant completed the paper-and-pencil
      version of the full 25-item THI before and after the 2-week EMA period. RESULTS:
      Participants responded to the alerts with a 90% compliance rate, providing a
      total of 1210 completed surveys. At the time of their response, participants
      indicated that they were in their house or apartment (67.7%), alone (50.2%),
      happy (50%), and calm (54.5%). Across most responses, participants could hear
      their tinnitus (97%), and the loudness of their tinnitus averaged 4.7 on a 7
      point increasing-loudness scale. The mean THI-S index score (out of a possible
      maximum 40 points for greatest tinnitus severity) was 17.0 (moderate self
      perceived tinnitus handicap). Repeated THI-S index scores varied considerably
      both within and between participants. Mean 25-item THI scores were not
      significantly different before and after the EMA period, suggesting little
      reactivity of the EMA. CONCLUSIONS: The high compliance rate, positive feedback
      from participants, lack of reactivity as a result of performing the EMA protocol,
      and data collected indicate that EMA methodology is feasible with patients who
      have tinnitus. Outcome data obtained with this methodology cannot be obtained any
      other way because retrospective questionnaires cannot capture the day-to-day
      reactions. This methodology has the potential to provide more in-depth and
      accurate assessments of patients receiving therapy for tinnitus.

PMID- 21960148
TI  - Wandering Ozurdex((r)) implant.
AB  - PURPOSE: To report the behavior of intravitreal Ozurdex((r)) implant in eyes with
      post-lensectomy-vitrectomy (PLV) aphakia. METHODS: Retrospective chart review of
      three eyes with PLV aphakia (three patients with uveitis) who received
      intravitreal injection of Ozurdex((r)) for cystoid macular edema (one eye),
      persistent inflammation (one eye), and ocular hypotony (one eye). Final outcome
      was assessed in terms of effectiveness, stability, and tolerance of the implant.
      RESULTS: Following the implant, an initial improvement was seen in all the three
      eyes. However, the implant migrated into the anterior chamber (AC) at 1 week in
      two eyes and at 5 weeks in one eye, and wandered between the AC and vitreous
      cavity with changing postures of the patient. Two eyes developed corneal edema,
      of which one eye underwent implant removal from the AC. CONCLUSION: Ozurdex((r))
      implant should be contraindicated in eyes with PLV aphakia to avoid its
      deleterious effect on the corneal endothelium.

PMID- 21960149
TI  - Functionalized fluorescent gold nanodots: synthesis and application for Pb2+
      sensing.
AB  - We developed a novel strategy to prepare functionalized fluorescent gold nanodots
      (AuNDs) based on a ligand exchange reaction and demonstrated that glutathione
      modified AuNDs can be utilized for highly sensitive and selective Pb(2+) sensing
      in aqueous solution.

PMID- 21960151
TI  - Drug dosing and monitoring in obese patients undergoing allogenic stem cell
      transplantation.
AB  - BACKGROUND: The effects of physiological changes in patients with obesity on
      pharmacokinetic parameters and the time course of drug response, especially in
      the field of haematology/oncology, are poorly understood. For some antimicrobial
      drugs, dosing considerations exist, while for cytostatic drugs, dose
      modifications for obese patients are not consistently recommended. Glomerular
      filtration rate and renal perfusion appear to be similar in obese and normal
      weight individuals, thus elimination of hydrophilic and extensively renally
      cleared drugs mainly depends upon creatinine clearance. AIM OF THE REVIEW: To
      provide information about drug dosing in morbidly obese patients undergoing
      allogenic haematopoietic stem cell transplantation and to develop dosing
      recommendations for those patients, based on literature data, pharmacokinetic
      properties and own experiences. METHOD: A review on the literature on drug dosing
      in obese patients as well as on the pharmacokinetic properties of drugs which are
      supposed to be used in the field of stem cell transplantation was combined with
      own data on drug dosing and pharmacokinetic drug monitoring in a morbidly obese
      patient undergoing matched-unrelated allogenic peripheral blood stem cell
      transplantation. RESULTS: For hydrophilic and extensively renally cleared drugs
      (e.g. piperacillin/sulbactam, cotrimoxazole, fludarabine) standard dosages for
      adult patients or dosing based on ideal body weight (IBW) (e.g. aciclovir,
      methotrexate) can be used. For ciclosporin and digitoxin we could show that high
      initial doses are needed to achieve sufficient plasma concentrations. After
      steady state distribution was completed, maintenance doses comparable to normal
      weight patients are sufficient. Likewise, distribution of enoxaparin and
      phenytoin seems to take longer in obese patients. Dosing recommendations of 25
      drugs that can be used in morbidly obese patients undergoing allogenic stem cell
      transplantation are given. CONCLUSIONS: Pharmacotherapy in morbidly obese
      patients undergoing allogenic stem cell transplantation is possible, if
      pharmacokinetic properties of the drugs are considered and close monitoring of
      plasma concentrations is performed.

PMID- 21960152
TI  - A comparative pilot study of the professional ethical thinking of Quebec pharmacy
      residents and French pharmacy interns.
AB  - OBJECTIVE: The main objective of this pilot study is to compare the professional
      ethical thinking of Quebec pharmacy residents and French pharmacy interns. The
      secondary objective is to compare the professional ethical thinking of Quebec
      pharmacy residents and first year French pharmacy interns. SETTING: Hospital
      pharmacy residents from Quebec, Canada and pharmacy interns from France. METHODS:
      This is a cross-sectional, descriptive, web-based survey. MAIN OUTCOME MEASURE:
      For this study, professional ethical thinking was defined as the level of
      agreement/disagreement with statements about pharmacy ethics/dilemmas. RESULTS: A
      total of 208 usable questionnaires were completed (response rate 91% in Quebec
      and 11% in France). There were no significant differences between Quebec
      residents and French interns for 29/43 items (67%). However, there were
      significant differences in their level of agreement with 14/43 items (33%)
      surveyed by our questionnaire. The differences related to the following themes:
      economic aspects (four statements), pharmaceutical care, code of ethics,
      evaluation, clinical research (two statements each) and training and education,
      dispensing medications (one statement each). There were statistically significant
      differences between the two groups in terms of exposure to ethics during academic
      training and experiential practice. There were significant statistical
      differences between the two groups of first year pharmacy respondents for 11
      statements (26%), with only two out of 11 statements being different from those
      reported in the overall comparison. CONCLUSION: Published data on the
      professional ethical thinking of pharmacy residents and interns remain limited.
      We believe the higher exposure of Quebec residents to ethics during academic
      courses and experiential/practical training may have contributed to a higher
      level of agreement with some ethical statements.

PMID- 21960153
TI  - Preferred structures of the atomic Ag islands on silicone oil surfaces.
AB  - Varying the substrate temperature T(s) from 285 to 353 K, both the aggregation
      behavior of Ag atoms and the preferred structures of the atomic Ag islands on
      silicone oil surfaces are investigated. After deposition, the deposited Ag atoms
      form isolated islands with a preferred height. Our observations reveal that, as
      T(s) increases, the preferred island height increases from 20.0 to 33.0 nm, which
      results in the decrease of the Ag apparent coverage, from 9.6 +/- 0.1% to 6.5 +/-
      0.3%. Further, the crystal structure of the Ag islands changes from amorphous to
      polycrystalline as the substrate temperature T(s) goes up. Subsequently a 3D
      aggregation mechanism of the Ag atoms on the liquid substrates is proposed.

PMID- 21960154
TI  - Diagnostic performance tests for suspected scaphoid fractures differ with
      conventional and latent class analysis.
AB  - BACKGROUND: Evaluation of the diagnostic performance characteristics of
      radiographic tests for diagnosing a true fracture among suspected scaphoid
      fractures is hindered by the lack of a consensus reference standard. Latent class
      analysis is a statistical method that takes advantage of unobserved, or latent,
      classes in the data that can be used to determine diagnostic performance
      characteristics when there is no consensus reference (gold) standard. PURPOSES:
      We therefore compared the diagnostic performance characteristics of MRI, CT, bone
      scintigraphy, and physical examination to identify true fractures among suspected
      scaphoid fractures. PATIENTS AND METHODS: We used data from two studies, one that
      prospectively studied 34 patients who had MRI and CT of the wrist, and a second
      that studied 78 patients who had MRI, bone scintigraphy, and structured physical
      examination. We compared the diagnostic performance characteristics calculated by
      latent class analysis with those calculated using formulas based on a reference
      standard. RESULTS: In the first cohort, the calculated sensitivity and
      specificity with latent class analysis were different than those with traditional
      reference standard-based calculations for the CT in the scaphoid planes
      (sensitivity, 0.78 versus 0.67; specificity, 1.0 versus 0.96) and the MRI
      (sensitivity, 0.80 versus 0.67; specificity, 0.93 versus 0.89). In the second
      cohort, the greatest differences were in the sensitivity of MRI (0.84 versus
      0.75) and the sensitivities of physical examination maneuvers (range, 0.63-0.73
      versus 1.0). CONCLUSIONS: The diagnostic performance characteristics calculated
      using latent class analysis may differ from those calculated according to
      formulas based on a reference standard. We believe latent class analysis merits
      further study as an option for assessing diagnostic performance characteristics
      for orthopaedic conditions when there is no consensus reference standard. LEVEL
      OF EVIDENCE: Level II, prognostic study. See the Guidelines for Authors for a
      complete description of levels of evidence.

PMID- 21960155
TI  - Early complications of high-dose-rate brachytherapy in soft tissue sarcoma: a
      comparison with traditional external-beam radiotherapy.
AB  - BACKGROUND: Radiotherapy and surgery are routinely utilized to treat extremity
      soft tissue sarcoma. Multiple radiation modalities have been described, each with
      advantages and disadvantages, without one modality demonstrating clear
      superiority over the others. QUESTIONS/PURPOSES: We determined the overall
      initial complication rate in patients receiving surgery and radiotherapy, which
      specific complications were found when comparing different modalities, and
      whether combination therapy increased the overall rate of complications compared
      with surgery and single-modality radiotherapy. PATIENTS AND METHODS: We
      retrospectively reviewed the records of 190 patients who received external-beam
      radiotherapy (141 patients), high-dose-rate brachytherapy (37 patients), or both
      (12 patients). We evaluated 100 men and 90 women (mean age, 57 years; range, 18
      94 years) for tumor size and subtype, comorbidities, stage, grade, margin of
      resection, type of adjuvant treatment, and complications. Minimum followup was 3
      months (mean, 40 months; range, 3-155 months). RESULTS: The most frequent early
      complications in the high-dose-rate brachytherapy cohort were infection,
      cellulitis, and seroma and/or hematoma. In the external-beam radiotherapy cohort,
      chronic edema, fibrosis, and chronic radiation dermatitis were more frequently
      encountered. The total number of early complications and overall incidence of
      major complications requiring further surgery were similar among the three
      cohorts, but a larger number of patients in the high-dose-rate brachytherapy
      group required subsequent surgery for infection compared with the external-beam
      radiotherapy group. CONCLUSIONS: High-dose-rate brachytherapy decreases radiation
      exposure and allows shorter duration of treatment compared with traditional
      external-beam radiotherapy but has a higher perioperative wound complication
      rate. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 21960156
TI  - Can a periarticular levobupivacaine injection reduce postoperative opiate
      consumption during primary hip arthroplasty?
AB  - BACKGROUND: Several reports have confirmed the ability of intraoperative
      periarticular injections to control pain after THA. However, these studies used
      differing combinations of analgesic agents and the contribution of each,
      including the local anesthetic agent, is uncertain. Understanding the independent
      effects of the various agents could assist in improved pain management after
      surgery. QUESTIONS/PURPOSES: We therefore determined the ability of
      intraoperative periarticular infiltration of levobupivacaine to (1) reduce
      postoperative pain, (2) reduce postoperative morphine requirements, and (3)
      reduce the incidence of nausea and urinary retention. PATIENTS AND METHODS: A
      double-blinded, randomized, placebo-controlled trial of patients undergoing
      primary THAs was performed. Patients were randomized to receive a periarticular
      infiltration of 150 mg levobupivacaine in 60 mL 0.9% saline (n = 45) or a placebo
      consisting of 60 mL 0.9% saline (n = 46). We obtained a short-form McGill pain
      score, visual analog scale (VAS), and morphine requirements via patient
      controlled analgesia (PCA) as primary measures. Postoperative antiemetic
      requirements and need for catheterization for urinary retention were determined
      as secondary measures. RESULTS: Subjectively reported pain scores and the overall
      intensity scores were similar for both groups in the postoperative period. At the
      same time the mean morphine consumption was less in the levobupivacaine group,
      most notable in the first 12 hours after surgery: treatment group 11.5 mg vs
      control group 21.2 mg. We observed no differences in the frequency of
      postoperative nausea and vomiting or urinary retention. CONCLUSIONS: Our
      observations suggest periarticular injection of levobupivacaine can supplement
      available postoperative analgesic techniques and reduce postoperative morphine
      requirements after THA. LEVEL OF EVIDENCE: Level I, therapeutic study. See
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 21960157
TI  - The value of perfusion CT in predicting the short-term response to synchronous
      radiochemotherapy for cervical squamous cancer.
AB  - OBJECTIVE: To determine the value of the perfusion parameters in predicting short
      term tumour response to synchronous radiochemotherapy for cervical squamous
      carcinoma. METHODS: Ninety-three patients with cervical squamous carcinoma later
      than stage IIB were included in this study. Perfusion CT was performed for all
      these patients who subsequently received the same synchronous radiochemotherapy.
      The patients were divided into responders and non-responders according to short
      term response to treatment. Baseline perfusion parameters of the two groups were
      compared. The perfusion parameters that might affect treatment effect were
      analysed by using a multivariate multi-regression analysis. RESULTS: The
      responders group had higher baseline permeability-surface area product (PS) and
      blood volume (BV) values than the non-responders group (P < 0.05). There was no
      statistical difference in baseline mean transit time (MTT) and blood flow (BF)
      value between the two groups (P >0.05). At multivariate multi-regression
      analysis, BV, PS and tumour size were significant factors in the prediction of
      treatment effect. Small tumours usually had high PS and BV values, and thus had a
      good treatment response. CONCLUSION: Perfusion CT can provide some helpful
      information for the prediction of the short-term effect. Synchronous
      radiochemotherapy may be more effective in cervical squamous carcinoma with
      higher baseline PS and BV. KEY POINTS: * Perfusion CT can reflect tumour vascular
      physiology in cervical squamous carcinoma. * Perfusion CT helps predict the short
      term effect before treatment * Synchronous radiochemotherapy may be more
      effective in patients with higher baseline BV and PS.

PMID- 21960158
TI  - The vestibulocochlear nerve: aplasia and hypoplasia in combination with inner ear
      malformations.
AB  - OBJECTIVE: To determine features of hypoplasia and aplasia of the
      vestibulocochlear nerve (VCN) in combination with inner ear malformations (IEMs).
      METHODS: Index cases were retrospectively selected from all IEMs collected since
      1995. CT and MRI data were reviewed by two neuroradiologists. The number and
      thickness of visible nerves in the cerebellopontine angle cistern and inside the
      internal auditory canal (IAC) were analysed. RESULTS: MR images for 176 patients
      with IEMs were analysed. Labyrinthine aplasia and otocyst deformity showed 100%
      correlation, and IAC malformations exhibited 92% correlation with VCN aplasia.
      Cochlear aplasia, complete aplasia of the semicircular canals, severe cochlear
      hypoplasia, common cavity, incomplete partition type 1 and mild cochlear
      hypoplasia showed decreasing degrees of correlation with hypoplasia of the VCN.
      The remaining types of IEM did not demonstrate VCN hypoplasia. CONCLUSIONS:
      Certain forms of IEM show 100% correlation with hypoplasia or aplasia of the VCN,
      while others correlate less strongly and some do not usually exhibit VCN
      hypoplasia. MRI should always be carried out for those forms often correlated
      with VCN hypoplasia. KEY POINTS: Vestibulocochlear nerve deficiency can be
      strongly suspected in certain inner ear malformations * Bony cochlear aplasia and
      cochlear nerve aplasia are strongly correlated * In semicircular canal aplasia,
      hypoplasia of the vestibular nerve can be found * Before cochlear implantation,
      the type of any IEM should be fully understood.

PMID- 21960160
TI  - Performing MR-guided biopsies in clinical routine: factors that influence
      accuracy and procedure time.
AB  - OBJECTIVE: To assess the accuracy, the duration and factors that influence the
      duration of MRI-guided liver or soft-tissue biopsies. METHODS: Nineteen liver
      biopsies and 19 soft-tissue biopsies performed using 1.5T-MRI guidance were
      retrospectively analysed. Diagnostic performance and complications were assessed.
      Intervention time was subdivided into preparation period, puncture period and
      control period. Correlation between procedure time and target size, skin-to
      target-distance, used sequences and interventionalists' experience were analysed.
      RESULTS: Overall sensitivity, specificity and accuracy were 0.86, 1.0 and 0.92,
      respectively. Two minor complications occurred. Overall median procedure time was
      103.5 min. Liver biopsies lasted longer than soft-tissue biopsies (mean([soft
      tissue]): 73.0 min, mean([liver]): 134.1 min, P < 0.001). The most time consuming
      part was the preparation period in both, soft-tissue and liver biopsies
      corresponding to 59.6% and 47.4% of the total intervention time, respectively.
      Total procedure time in liver biopsies (P = 0.027) and puncture period in liver
      and soft-tissue biopsies (P ([liver]) = 0.048, P ([soft-tissue]) = 0.005) was
      significantly prolonged for longer skin-to-target-distances. Lower numbers of
      image acquisitions (P ([liver]) = 0.0007, P ([soft-tissue]) = 0.0012) and
      interventionalists' experience reduces the procedure duration significantly (P <
      0.05), besides all false-negative results appeared during the first five biopsies
      of each individual radiologist. CONCLUSION: The interventionalists' experience,
      skin-to-target-distances and number of image acquisition influence the procedure
      time significantly. KEY POINTS: *Appropriate training and supervision is
      essential for inexperienced interventionalists. *Two perpendicular image
      orientations should confirm the correct biopsy needle position. *Communication
      between interventionalist and technician is essential for a fluent biopsy
      procedure. *To shorten intervention time appropriate previous imaging is
      essential.

PMID- 21960159
TI  - Systematic review: bias in imaging studies - the effect of manipulating clinical
      context, recall bias and reporting intensity.
AB  - OBJECTIVES: To perform a systematic review of diagnostic test accuracy studies
      which manipulate or investigate the context of interpretation. In particular,
      those which modify or conceal sample characteristics (e.g. disease prevalence or
      reporting intensity) or research setting ("laboratory" versus "field"). We also
      investigated recall bias. METHODS: We searched the biomedical literature to March
      2010 using 3 complementary strategies. Inclusion criteria were: imaging studies
      quantifying the effect on diagnosis of modifying the context of observers'
      interpretations, varying disease prevalence, concealing sample characteristics,
      reporting intensity and recall bias. RESULTS: 11247 abstracts were reviewed, 201
      full texts examined and 12 ultimately included. There were 5 to 9520 patients and
      2 to 129 observers per study. Nine studies investigated clinical review bias of
      sample level information. Only 3 studies investigated prevalence, 2 of which
      investigated maximum enrichment well below the levels often used by researchers.
      We identified no research specifically directed at concealing disease prevalence.
      Available research found no evidence of recall bias or "washout" on study
      results. CONCLUSIONS: Several sources of bias central to the design of diagnostic
      test accuracy studies are poorly researched; the implications for evidence-based
      practice remain uncertain. Research is suggested to guide methodological design,
      particularly in the context of screening. KEY POINTS: Imaging research studies
      often ignore the possible effect of disease prevalence It is unclear how the
      expectation of disease influences radiological interpretation The potential
      effect of observer recall bias is poorly researched Such factors might introduce
      bias into radiological research methodology This systematic review attempts to
      illustrate these points.

PMID- 21960161
TI  - Theoretical studies on interactions between low energy electrons and protein-DNA
      fragments: valence anions of AT-amino acids side chain complexes.
AB  - Electron attachment to trimeric complexes that mimic most frequent hydrogen
      bonding interactions between an amino acid side chain (AASC) and the Watson-Crick
      (WC) 9-methyladenine-1-methylthymine (MAMT) base pair has been studied at the
      B3LYP/6-31++G(d,p) level of theory. Although the neutral trimers will not occur
      in the gas phase due to unfavorable free energy of stabilization (G(stab)) they
      should form a protein-DNA complex where entropy changes related to formation of
      such a complex will more than balance its disadvantageous G(stab). The most
      stable neutrals possess an identical pattern of hydrogen bonds (HBs). In
      addition, the proton-acceptor (N7) and proton-donor (N10) atoms of adenine
      involved in those HBs are located in the main groove of DNA. All neutral
      structures support the adiabatically stable valence anions in which the excess
      electron is localized on a pi* orbital of thymine. The vertical detachment
      energies (VDEs) of anions corresponding to the most stable neutrals are
      substantially smaller than that of the isolated WC MAMT base pair. Hence,
      electron transfer from the anionic thymine to the phosphate group and as a
      consequence formation of a single strand break (SSB) should proceed more
      efficiently in a protein-dsDNA complex than in the naked dsDNA as far as electron
      attachment to thymine is concerned.

PMID- 21960162
TI  - Diffusion tensor imaging in the differentiation of adrenal adenomas and
      metastases.
AB  - PURPOSE: To determine the utility of diffusion tensor imaging for the
      differentiation of adrenal adenomas and metastases. MATERIALS AND METHODS: Thirty
      three patients with a mean age of 59 years were included in this study. Each
      subject presented with a single adrenal lesion (19 adenomas, 14 metastases).
      Magnetic resonance imaging (MRI) was performed in the coronal plane using a 3
      Tesla MRI and a six-channel phased array SENSE torso coil. T1-weighted in-phase
      and opposed-phase, T2-weighted turbo spin-echo, and single-shot echo-planar
      diffusion tensor imaging (DTI) sequences were used for image acquisition. To
      determine apparent diffusion coefficients (ADC) and fractional anisotropy (FA)
      values of adrenal lesions, coronal T2-weighted images were used as anatomical
      references and to localize regions of interest on DTI images. The signal
      intensity (SI) indices were obtained from in-phase/opposed-phase images by a
      radiologist blinded to the DTI findings. The DTI parameters were determined by a
      different radiologist. The SI indices and the differences in FA and ADCs between
      adenomas and metastases were compared. Analyses of receiver operating
      characteristics (ROC) were performed to determine the area under the curve (AUC).
      RESULTS: The SI index of adenomas was found to be significantly higher than the
      value determined for metastases. Moreover, the median FA value of adrenal
      adenomas was found to be significantly higher than that of metastases. No
      statistically significant difference was observed in the ADCs between adenomas
      and metastases. Furthermore, no significant correlation was found among the SI
      index and the measured DTI parameters. Based on ROC analyses, the AUC was found
      to be 0.936 in FA measurements with a 95% confidence interval. The cutoff value
      obtained from this analysis was 0.40 with maximum sensitivity and specificity
      values of 74% and 88%, respectively. CONCLUSION: Although no significant
      difference was observed in the ADCs between adrenal adenomas and metastases, the
      FA values differed significantly. The FA values may have the potential to
      differentiate between adrenal adenomas and metastases, which is a possibility
      that should be validated by further research.

PMID- 21960163
TI  - Mutation of OsALDH7 causes a yellow-colored endosperm associated with
      accumulation of oryzamutaic acid A in rice.
AB  - Aldehyde dehydrogenase proteins consist of a superfamily and the family 7 (ALDH7)
      is a typical group with highly conserved proteins across species. It catalyzes
      oxidation of alpha-aminoadipic semialdehyde (AASA) in lysine degradation,
      participates in protection against hyperosmotic stress, and detoxifies aldehydes
      in human; however, its function in plants has been much less documented. Here we
      reported a mutant with yellow-colored endosperm in rice, and showed that the
      yellow endosperm was caused by mutation of OsALDH7. OsALDH7 is expressed in all
      tissues detected, with the highest level in mature seeds. We found that
      oryzamutaic acid A accumulated during late seed development and after a year-long
      storage in the colored endosperm, whereas it was undetectable in the wild type
      endosperm. Moreover, lysine degradation was enhanced in yeast over-expressing
      OsALDH7 and as a result, content of lysine, glutamate and saccharopine was
      changed, suggesting a role of OsALDH7 in lysine catabolism.

PMID- 21960164
TI  - Proteomic analysis of a model unicellular green alga, Chlamydomonas reinhardtii,
      during short-term exposure to irradiance stress reveals significant down
      regulation of several heat-shock proteins.
AB  - Oxygenic photosynthetic organisms often suffer from excessive irradiance, which
      cause harmful effects to the chloroplast proteins and lipids. Photoprotection and
      the photosystem II repair processes are the mechanisms that plants deploy to
      counteract the drastic effects from irradiance stress. Although the protective
      and repair mechanisms seemed to be similar in most plants, many species do confer
      different level of tolerance toward high light. Such diversity may originate from
      differences at the molecular level, i.e., perception of the light stress, signal
      transduction and expression of stress responsive genes. Comprehensive analysis of
      overall changes in the total pool of proteins in an organism can be performed
      using a proteomic approach. In this study, we employed 2-DE/LC-MS/MS-based
      comparative proteomic approach to analyze total proteins of the light sensitive
      model unicellular green alga Chlamydomonas reinhardtii in response to excessive
      irradiance. Results showed that among all the differentially expressed proteins,
      several heat-shock proteins and molecular chaperones were surprisingly down
      regulated after 3-6 h of high light exposure. Discussions were made on the
      possible involvement of such down regulation and the light sensitive nature of
      this model alga.

PMID- 21960166
TI  - Hypothalamic gene changes in response to salt appetite.

PMID- 21960167
TI  - Renal ischemic preconditioning: finally some good news for prevention of acute
      kidney injury.
AB  - Recent clinical trials of remote ischemic preconditioning offer hope that this
      well-validated experimental method of protecting tissues against ischemic injury
      will provide a more robust alternative to pharmaceutical prevention against
      cardiac and renal ischemic injury.

PMID- 21960168
TI  - Immunosuppressive treatment of focal segmental glomerulosclerosis: lessons from a
      randomized controlled trial.
AB  - Patients with steroid-resistant focal segmental glomerulosclerosis (FSGS) may
      benefit from treatment with calcineurin inhibitors. A National Institutes of
      Health-funded FSGS multicenter study has suggested that a combination of
      mycophenolate mofetil and oral dexamethasone pulses was equivalent to
      cyclosporine. However, since the study was underpowered, one cannot draw firm
      conclusions from this study. The FSGS trial underscores that FSGS is not one
      disease and that better predictors of outcome and response to therapy are needed.

PMID- 21960169
TI  - Transplant glomerulopathy: it's not always about chronic rejection.
AB  - Transplant glomerulopathy (TG) is a morphologic lesion of renal allografts
      characterized by duplication of the glomerular basement membrane and is widely
      accepted as a manifestation of chronic antibody-mediated rejection (AMR).
      However, TG is not specific for chronic AMR, and this pattern of injury may
      result from a number of disease processes affecting the glomerular endothelium.
      Baid-Agrawal and co-workers consider three different, but not mutually exclusive,
      processes that can produce morphologic lesions of TG: chronic AMR, hepatitis C,
      and thrombotic microangiopathy.

PMID- 21960170
TI  - Olfactory function in dialysis patients: a potential key to understanding the
      uremic state.
AB  - Impaired olfactory function is a marker of neurologic dysfunction in the uremic
      state. Retained uremic toxins not adequately cleared with dialysis may undermine
      the integrity of the olfactory epithelium and olfactory bulb and malign central
      olfactory processing. The evidence suggests that only renal transplantation, with
      its concomitant thorough reversal of uremia, truly restores olfactory function to
      normal in end-stage renal disease. Testing of olfactory function may emerge as an
      important marker for the extent and resolution of uremia.

PMID- 21960171
TI  - Association with Helicobacter pylori infection and ghrelin level in hemodialysis
      patients.

PMID- 21960173
TI  - 'Walking-stick ureters' in ketamine abuse.

PMID- 21960174
TI  - Recipient-derived EDA fibronectin promotes cardiac allograft fibrosis.
AB  - Advances in donor matching and immunosuppressive therapies have decreased the
      prevalence of acute rejection of cardiac grafts; however, chronic rejection
      remains a significant obstacle for long-term allograft survival. While initiating
      elements of anti-allograft immune responses have been identified, the linkage
      between these factors and the ultimate development of cardiac fibrosis is not
      well understood. Tissue fibrosis resembles an exaggerated wound healing response,
      in which extracellular matrix (ECM) molecules are central. One such ECM molecule
      is an alternatively spliced isoform of the ubiquitous glycoprotein fibronectin
      (FN), termed extra domain A-containing cellular fibronectin (EDA cFN). EDA cFN is
      instrumental in fibrogenesis; thus, we hypothesized that it might also regulate
      fibrotic remodelling associated with chronic rejection. We compared the
      development of acute and chronic cardiac allograft rejection in EDA cFN-deficient
      (EDA(-/-)) and wild-type (WT) mice. While EDA(-/-) mice developed acute cardiac
      rejection in a manner indistinguishable from WT controls, cardiac allografts in
      EDA(-/-) mice were protected from fibrosis associated with chronic rejection.
      Decreased fibrosis was not associated with differences in cardiomyocyte
      hypertrophy or intra-graft expression of pro-fibrotic mediators. Further, we
      examined expression of EDA cFN and total FN by whole splenocytes under conditions
      promoting various T-helper lineages. Conditions supporting regulatory T-cell
      (Treg) development were characterized by greatest production of total FN and EDA
      cFN, though EDA cFN to total FN ratios were highest in Th1 cultures. These
      findings indicate that recipient-derived EDA cFN is dispensable for acute
      allograft rejection responses but that it promotes the development of fibrosis
      associated with chronic rejection. Further, conditions favouring the development
      of regulatory T cells, widely considered graft-protective, may drive production
      of ECM molecules which enhance deleterious remodelling responses. Thus, EDA cFN
      may be a therapeutic target for ameliorating fibrosis associated with chronic
      cardiac allograft rejection.

PMID- 21960176
TI  - Gender-related differences in octogenarians with congenital coronary artery
      fistula: a report of two cases and a review.
AB  - AIM: To highlight gender-related differences in octogenarians with a congenital
      coronary artery fistula (CAF). MATERIALS AND METHODS: We present two elderly
      female patients with a congenital fistula, a septuagenarian and a nonagenarian,
      and review the world literature between 1954-2010. RESULTS: The septuagenarian
      patient presented with easy fatigability and the nonagenarian patient with acute
      myocardial infarction contralaterally to the fistula. Coronary angiography (CAG)
      demonstrated a coronary-pulmonary artery fistula (CPF). The nonagenarian patient
      underwent percutaneous coronary intervention of the right coronary artery. CAG
      revealed a CPF associated with a huge multiple aneurysmal formation. Data from 57
      mainly symptomatic patients with a mean age of 75.3 years (range 70-87 years)
      were collected. The cohort was subdivided into female (mean age 84.3 years) and
      male (mean age 75.2 years) subgroups and compared with each other. Multi-origin
      (bilateral and multilateral) was prevalent in females, 40% versus 12% in males.
      Aneurysmal formation was found in females and males in 40% and 18%, respectively.
      Ethnicity was 65% Caucasian and 35% Asian. Multi-origin fistulas were prevalent
      in the Asian (45%) compared with the Caucasian (11%) subset. CONCLUSIONS: A
      septuagenarian and a nonagenarian female patient with congenital CAF are
      presented. On reviewing the literature, important differences were found between
      elderly females and males with congenital CAF.

PMID- 21960177
TI  - Two cases of left-sided and concomitant right-sided endocarditis: potential
      pathways of spreading.

PMID- 21960175
TI  - Multimodal wavelet embedding representation for data combination (MaWERiC):
      integrating magnetic resonance imaging and spectroscopy for prostate cancer
      detection.
AB  - Recently, both Magnetic Resonance (MR) Imaging (MRI) and Spectroscopy (MRS) have
      emerged as promising tools for detection of prostate cancer (CaP). However, due
      to the inherent dimensionality differences in MR imaging and spectral
      information, quantitative integration of T(2) weighted MRI (T(2)w MRI) and MRS
      for improved CaP detection has been a major challenge. In this paper, we present
      a novel computerized decision support system called multimodal wavelet embedding
      representation for data combination (MaWERiC) that employs, (i) wavelet theory to
      extract 171 Haar wavelet features from MRS and 54 Gabor features from T(2)w MRI,
      (ii) dimensionality reduction to individually project wavelet features from MRS
      and T(2)w MRI into a common reduced Eigen vector space, and (iii), a random
      forest classifier for automated prostate cancer detection on a per voxel basis
      from combined 1.5 T in vivo MRI and MRS. A total of 36 1.5 T endorectal in vivo
      T(2)w MRI and MRS patient studies were evaluated per voxel by MaWERiC using a
      three-fold cross validation approach over 25 iterations. Ground truth for
      evaluation of results was obtained by an expert radiologist annotations of
      prostate cancer on a per voxel basis who compared each MRI section with
      corresponding ex vivo wholemount histology sections with the disease extent
      mapped out on histology. Results suggest that MaWERiC based MRS T(2)w meta
      classifier (mean AUC, MU = 0.89 +/- 0.02) significantly outperformed (i) a T(2)w
      MRI (using wavelet texture features) classifier (MU = 0.55 +/- 0.02), (ii) a MRS
      (using metabolite ratios) classifier (MU = 0.77 +/- 0.03), (iii) a decision
      fusion classifier obtained by combining individual T(2)w MRI and MRS classifier
      outputs (MU = 0.85 +/- 0.03), and (iv) a data combination method involving a
      combination of metabolic MRS and MR signal intensity features (MU = 0.66 +/-
      0.02).

PMID- 21960178
TI  - Bone loss in adult offspring induced by low-dose exposure to teratogens.
AB  - Maternal malnutrition during pregnancy was shown by numerous studies to result in
      the birth of offspring exhibiting altered bone characteristics, which are
      indicative of bone loss. We hypothesized that not only maternal malnutrition but
      also some developmental toxicants (teratogens) given at a dose inducing neither
      structural anomalies nor growth retardation can detrimentally affect skeletal
      health in adult offspring. To check this hypothesis, pregnant mice were exposed
      to a single injection of 5-aza-2-deoxycytidine (5-AZA) (a teratogen capable of
      inducing phocomelia of the hind limbs) at a sub-threshold teratogenic dose. Micro
      computed tomography scanning revealed that femora of 5-month-old male offspring
      exposed in uterus to 5-AZA had trabecular microarchitecture indicative of bone
      loss. Furthermore, exposure to 5-AZA increased the susceptibility of offspring to
      postnatal chronic mild stress, which has been shown to induce bone loss in mice.
      While exploring possible mechanisms underlying this phenomenon, we observed that
      the expression of some microRNAs, which have been demonstrated as regulators of
      key osteoblastogenic genes, was altered in hind limb buds of embryos exposed to 5
      AZA. Furthermore, the expression of receptor activator of nuclear factor kappa B
      ligand (RANKL) in femoral stromal/osteoblastic cells of 5-month-old offspring of
      5-AZA-treated females was found to be increased. Collectively, this study implies
      for the first time that single low-dose exposure to a teratogen can induce bone
      loss in adult offspring, possibly via alteration of embryonic microRNAs and RANKL
      expression.

PMID- 21960179
TI  - Role of osteoclasts and interleukin-17 in the pathogenesis of rheumatoid
      arthritis: crucial 'human osteoclastology'.
AB  - Many papers have reported that osteoclasts play an important role in the
      pathogenesis of rheumatoid arthritis (RA); however, when we started to
      investigate the pathogenesis of RA, the roles of osteoclasts were not highlighted
      in RA bone resorption. In recent years, the number of articles on the roles of
      osteoclasts and interleukin (IL)-17 in the pathogenesis of RA has increased
      exponentially. In this review article, we describe our articles on the roles of
      osteoclasts and IL-17 in joint destruction in RA, from 1990 to 2011, and
      highlight a novel term, 'human osteoclastology', which we have used since 2008.

PMID- 21960180
TI  - Depot naltrexone decreases rewarding properties of sugar in patients with opioid
      dependence.
AB  - BACKGROUND: Opioid neurotransmission mediates hedonic value of sweet tastants;
      their intake may be exaggerated by the consumption of exogenous opioids (e.g.,
      opioid dependence). Sweet Taste Test (STT) is a validated quantitative instrument
      assessing taste perception and hedonic features of sugar (sucrose) using a
      randomized and double-blind administration at five different sucrose
      concentrations ranging from 0.05 to 0.83 M. METHODS: The STT and cue-induced
      craving procedure were administered to opioid-dependent patients (n = 15) before
      and 1 week after the injection of a long-acting depot naltrexone (XRNT)
      preparation. RESULTS: Analyses of covariance, employing sucrose concentration and
      its perceived taste as covariates, showed that XRNT therapy significantly reduced
      the self-reported hedonic and motivational characteristics of sucrose. Greater
      reductions in both these characteristics were associated with more diminution in
      the cue-induced opioid craving. CONCLUSIONS: Opioid antagonism in opioid
      dependent subjects leads to a smaller sweet taste reward, which, in turn, may be
      proportional to decreased opioid craving. These pilot results support the
      heuristic value of the STT as a potential marker of the XRNT treatment response
      and call for further inquiry into potential clinical applications of the test.

PMID- 21960181
TI  - Delivery of nicotine in an extract of a smokeless tobacco product reduces its
      reinforcement-attenuating and discriminative stimulus effects in rats.
AB  - RATIONALE: Animal models of tobacco addiction rely on administration of nicotine
      alone or nicotine combined with isolated constituents. Models using tobacco
      extracts derived from tobacco products and containing a range of tobacco
      constituents might more accurately simulate tobacco exposure in humans.
      OBJECTIVE: To compare the effects of nicotine alone and an aqueous smokeless
      tobacco extract in several addiction-related animal behavioral models. METHODS:
      Nicotine alone and nicotine dose-equivalent concentrations of extract were
      compared in terms of their acute effects on intracranial self-stimulation (ICSS)
      thresholds, discriminative stimulus effects, and effects on locomotor activity.
      RESULTS: Similar levels of nicotine and minor alkaloids were achieved using
      either artificial saliva or saline for extraction, supporting the clinical
      relevance of the saline extracts used in these studies. Extract produced
      reinforcement-enhancing (ICSS threshold-decreasing) effects similar to those of
      nicotine alone at low to moderate nicotine doses, but reduced reinforcement
      attenuating (ICSS threshold-increasing) effects at a high nicotine dose. In rats
      trained to discriminate nicotine alone from saline, intermediate extract doses
      did not substitute for the training dose as well as nicotine alone. Locomotor
      stimulant effects and nicotine distribution to brain were similar following
      administration of extract or nicotine alone. CONCLUSIONS: The reinforcement
      attenuating and discriminative stimulus effects of nicotine delivered in an
      extract of a commercial smokeless tobacco product differed from those of nicotine
      alone. Extracts of tobacco products may be useful for evaluating the abuse
      liability of those products and understanding the role of non-nicotine
      constituents in tobacco addiction.

PMID- 21960182
TI  - Acute tolerance to alcohol impairment of behavioral and cognitive mechanisms
      related to driving: drinking and driving on the descending limb.
AB  - RATIONALE: Alcohol effects on behavioral and cognitive mechanisms influence
      impaired driving performance and decisions to drive after drinking (Barry 1973;
      Moskowitz and Robinson 1987). To date, research has focused on the ascending limb
      of the blood alcohol curve, and there is little understanding of how acute
      tolerance to impairment of these mechanisms might influence driving behavior on
      the descending limb. OBJECTIVES: To provide an integrated examination of the
      degree to which alcohol impairment of motor coordination and inhibitory control
      contributes to driving impairment and decisions to drive on the ascending and
      descending limbs of the blood alcohol curve. METHODS: Social-drinking adults (N =
      20) performed a testing battery that measured simulated driving performance and
      willingness to drive, as well as mechanisms related to driving: motor
      coordination (grooved pegboard), inhibitory control (cued go/no-go task), and
      subjective intoxication. Performance was tested in response to placebo and a
      moderate dose of alcohol (0.65 g/kg) twice at comparable blood alcohol
      concentrations: once on the ascending limb and again on the descending limb.
      RESULTS: Impaired motor coordination and subjective intoxication showed acute
      tolerance, whereas driving performance and inhibitory control showed no recovery
      from impairment. Greater motor impairment was associated with poorer driving
      performance under alcohol, and poorer inhibitory control was associated with more
      willingness to drive. CONCLUSIONS: Findings suggest that acute tolerance to
      impairment of motor coordination is insufficient to promote recovery of driving
      performance and that the persistence of alcohol-induced disinhibition might
      contribute to risky decisions to drive on the descending limb.

PMID- 21960183
TI  - Nanoscale three-dimensional single particle tracking.
AB  - Single particle tracking (SPT) in biological systems is a quickly growing field.
      Many new technologies are being developed providing new tracking capabilities,
      which also lead to higher demands and expectations for SPT. Following a single
      biomolecule as it performs its function provides quantitative mechanistic
      information that cannot be obtained in classical ensemble methods. From the 3D
      trajectory, information is available over the diffusional behavior of the
      particle and precise position information can also be used to elucidate
      interactions of the tracked particle with its surroundings. Thus, three
      dimensional (3D) SPT is a very valuable tool for investigating cellular
      processes. This review presents recent progress in 3D SPT, from image-based
      techniques toward more sophisticated feedback approaches. We focus mainly on the
      feedback technique known as orbital tracking. We present here a modified version
      of the original orbital tracking in which the intensities from two z-planes are
      simultaneously measured allowing a concomitant wide-field imaging. The system can
      track single particles with a precision down to 5 nm in the x-y plane and 7 nm in
      the axial direction. The capabilities of the system are demonstrated using single
      virus tracing to follow the infection pathway of Prototype Foamy Virus in living
      cells.

PMID- 21960184
TI  - Adiponectin levels in patients with colorectal cancer and adenoma:  a meta
      analysis.
AB  - Inconsistent results with regard to adiponectin levels in patients with
      colorectal cancer (CRC) and adenoma have been reported. To evaluate adiponectin
      levels in patients with CRC and adenoma, a meta-analysis on studies which
      compared adiponectin levels in patients with CRC or adenoma with healthy controls
      was carried out. A literature search was performed through Pubmed, EMBASE, and
      Science Citation Index Expanded database. Pooled-weighted mean differences and
      95% confidence intervals (95%CI) were calculated by using random-effects models.
      Heterogeneity between studies was assessed using the Cochran's Q and I
      statistics. A total of 13 studies were identified, which included 2632 cases of
      CRC or adenoma and 2753 healthy controls. Adiponectin levels were significantly
      lower in patients with CRC or adenoma compared with healthy controls, with
      significant heterogeneity [weighted mean differences of -1.51 (95% CI: -2.42 to 
      0.59; Pheterogeneity<0.001) for CRC and -1.29 (95% CI: -2.01to -0.58;
      Pheterogeneity<0.001) for colorectal adenoma, respectively]. On stratified
      analysis of CRC, significant difference in adiponectin levels between patients
      with CRC and healthy controls was reported only in case-control studies or small
      sample size studies (n<100), but not in nested case-control studies or large
      sample size studies (n>=100). In addition, metaregression analysis indicated that
      study design and sample size partly contributed to the significant heterogeneity
      (P=0.022 for study design and P=0.018 for sample size, respectively). For
      colorectal adenoma studies, stratified analysis indicated that sample size was
      one of the heterogeneous factors. Sensitivity analysis showed that there were no
      changes in the direction of effect when any one study was excluded. No
      publication bias was detected. Adiponectin levels are lower in patients with CRC
      or colorectal adenoma compared with those in healthy controls. Future studies are
      warranted to clarify the association of adiponectin levels and carcinogenesis of
      the colorectum.

PMID- 21960185
TI  - Mortality causes in cancer patients with type 2 diabetes mellitus.
AB  - Cancer patients diagnosed with type 2 diabetes mellitus (T2DM) are at an
      increased risk of death due to cancer. However, whether T2DM comorbidity
      increases other causes of death in cancer patients is the novel theme of this
      study. Patients with T2DM were identified from the nationwide Swedish Hospital
      Discharge Register and linked with patients with cancer recorded from the Swedish
      Cancer Registry. Hazard ratios (HRs) were calculated for death due to all causes
      among cancer patients with and without T2DM; both underlying and multiple causes
      of death were examined using the Cox regression model. A total of 13 325 cancer
      patients were identified with comorbidity of T2DM. The total number of deaths of
      cancer patients was 276 021. Of these, 5900 occurred after T2DM diagnosis. For
      underlying causes of death, except for T2DM, the highest cause-specific HRs were
      found for complications of bacterial disease (HR, 3.93; 95% CI, 3.04-5.09),
      urinary system disease (HR, 3.39; 95% CI, 2.78-4.12), and myocardial infarction
      (HR, 2.93; 95% CI, 2.75-3.12). When risk of death was examined for both
      underlying and multiple causes of death, the highest HRs were found for
      hypertensive disease (HR, 3.42; 95% CI, 3.15-3.72), urinary system disease (HR,
      3.39; 95% CI, 3.17-3.63), and arterial disease (HR, 3.26; 95% CI, 3.08-3.46). The
      diagnosis of T2DM in cancer patients is associated with an increased risk of
      death due to various causes, including myocardial infarction, other bacterial
      disease, urinary system disease, hypertensive disease, arterial disease, and so
      on, which may be related to both cancer and treatment. Clinicians that treat
      cancer patients with T2DM should pay more attention to comorbidities.

PMID- 21960186
TI  - Safety and immunogenicity of a 13-valent pneumococcal conjugate vaccine in
      healthy infants and toddlers given with routine pediatric vaccinations in Canada.
AB  - BACKGROUND: The global distribution of pneumococcal disease and emergence of
      nonvaccine pneumococcal serotypes prompted the development of a 13-valent
      pneumococcal conjugate vaccine (PCV13), with broader coverage than 7-valent PCV
      (PCV7). This study compared compatibility of PCV13 and PCV7 with concurrently
      administered diphtheria, tetanus, acellular pertussis, inactivated poliovirus,
      Haemophilus influenzae type b vaccine, and meningococcal C conjugate vaccine
      (menC), and assessed the safety and immunogenicity of PCV13. METHODS: In this
      double-blind, randomized trial, children received PCV7 or PCV13 at 2, 4, 6, and
      12 months with routine vaccinations. One month following the infant series and
      toddler dose, the responses to Hib, pertussis, menC, and specific pneumococcal
      serotypes were measured. Safety and tolerability were assessed daily for 4 days
      by parents. RESULTS: Subjects received PCV13 (n = 300) or PCV7 (n = 303);
      immunogenicity assessment was completed in 265 and 268 subjects, respectively.
      There were no statistically significant differences between the groups in
      responses to Hib, pertussis, or menC after primary or booster vaccinations. More
      than 95% of subjects in the PCV13 group produced >0.35 MUg/mL antibody to each
      pneumococcal serotype 1 month after the third dose, except with serotypes 23F
      (90%), 3 (80%), and 5 (87%). After the fourth dose, 98% to 100% of subjects
      achieved serotype-specific antibody concentrations >0.35 MUg/mL, except for
      serotype 3 (85%). Safety and tolerability did not differ between groups with
      respect to local or systemic side effects. CONCLUSIONS: Responses to routine
      childhood vaccines did not differ with PCV7 or PCV13 coadministration. Serotype
      specific pneumococcal antibody concentrations were protective. The safety profile
      of PCV13 was favorable.

PMID- 21960187
TI  - Cost-effectiveness of palivizumab for respiratory syncytial virus infection in
      high-risk children, based on long-term epidemiologic data from Austria.
AB  - OBJECTIVE: To assess the cost-effectiveness of palivizumab, a monoclonal antibody
      against respiratory syncytial virus (RSV), in infants at high risk for severe RSV
      lower respiratory tract infection, such as premature infants, infants with
      bronchopulmonary dysplasia, and those with congenital heart disease, based on
      long-term epidemiologic data from Austria. METHODS: A decision-tree model was
      used, and the analysis was based on a lifetime follow-up investigating cost
      effectiveness of palivizumab versus no RSV infection prevention. The primary
      perspective of the study was that of the healthcare system, the second that of
      society. Cost and effects were discounted by 5%. The base case analysis included
      only direct medical costs, and a scenario analysis included various indirect
      costs. RESULTS: Analyses were based on epidemiologic data on a total of 1579
      children hospitalized because of RSV lower respiratory tract infection during 16
      seasons. The incremental cost-effectiveness ratio for the first outcome measure
      (life years gained) amounted to discounted costs of ?34,956 (for all preterm
      infants), ?35,056 (for < 33 weeks' gestational age [wGA] infants), ?35,233 (for
      33-35 wGA infants), ?35,611 (for infants with bronchopulmonary dysplasia), and
      ?8956 (for infants with congenital heart disease). Use of palivizumab compared
      with no prophylaxis had an incremental cost-utility ratio of ?26,212, ?26,292,
      ?24,392, ?24,654, and ?8484, respectively, per quality-adjusted life years.
      Results from the society perspective were more cost-effective in all study
      populations. An additional scenario analysis with 7 injections for the 33 to 35
      wGA group revealed cost-effectiveness as well. CONCLUSIONS: Our results based on
      nationwide long-term epidemiologic data suggest that palivizumab is cost
      effective in prevention of RSV disease in high-risk infants.

PMID- 21960189
TI  - Adapting to change.

PMID- 21960188
TI  - Dealing with complexity through more robust approaches to the evidence-based
      design of healthcare facilities.

PMID- 21960190
TI  - Integrating evidence-based design and experience-based approaches in healthcare
      service design.
AB  - OBJECTIVE: To investigate the connections between, and respective contributions
      of, evidence-based and experience-based methods in the redesign of healthcare
      services. BACKGROUND: Evidence-based medicine (EBM) preceded (and inspired) the
      development of evidence-based design (EBD) for healthcare facilities. A key
      feature of debate around EBM has been the question of interpretation of the
      guidance by experienced clinicians, to achieve maximum efficacy for individual
      patients. This interpretation and translation of guidelines-avoiding a formulaic
      approach, allowing for divergent cultural and geographical exigencies, creating
      innovative, context-specific solutions-is the subject of this discussion, which
      examines the potential for integration of evidence-based and experience-based
      approaches in the development of creative solutions to healthcare services in
      England. This paper examines Practice-Based Commissioning (PBC) in England, which
      devolves responsibility for commissioning new services for patients to frontline
      clinicians, relying on their understanding of patient needs at the local level.
      METHODS: An 18-month project, funded by the Health and Care Infrastructure
      Research and Innovation Centre (HaCIRIC), examined PBC frameworks in England,
      investigating the impact of different models of governance on the development of
      service redesign proposals to answer the following questions: How do clinicians
      interpret the multiplicity of guidance from government agencies and translate
      this into knowledge that can be effectively used to redesign patient care
      pathways aligned with local healthcare priorities? How can understanding patient
      and staff "experiences" and key "touch points" of interaction with local
      healthcare services be used to provide a creative, customized solution to the
      design of healthcare services in a local, community-based framework?

PMID- 21960191
TI  - Quantifying the relationship among hospital design, satisfaction, and
      psychosocial functioning in a pediatric hematology-oncology inpatient unit.
AB  - BACKGROUND: Studies show that hospital built environments can affect physical and
      psychological outcomes and healthcare satisfaction in adults, but pediatric
      research is sparse. OBJECTIVE: To investigate the effects of the built
      environment on hospitalized pediatric hematology-oncology patients and their
      parents by testing the hypothesis that perceived built environment satisfaction
      mediates the relationship between the objective built environment and
      psychosocial functioning, as well as parental healthcare satisfaction. METHODS:
      The hospital built environment was evaluated subjectively through the PedsQLTM
      Hospital Healing Environment Module satisfaction questionnaires and objectively
      by quantifying environmental features. Outcomes for patients and parents included
      present functioning and affect. Healthcare satisfaction was also assessed for
      parents. Structural equation modeling (SEM) was used to test the mediational
      hypothesis. SUBJECTS: Participants were 90 hospitalized pediatric hematology
      oncology patients and 149 parents of pediatric hematology-oncology patients.
      RESULTS: For both parents and children, analyses revealed a significant positive
      relationship between the quality of the objective built environment and built
      environment satisfaction. For parents, significant relationships emerged in the
      expected direction between built environment satisfaction and present
      functioning, healthcare satisfaction, and negative affect. CONCLUSIONS: Both
      pediatric hematology-oncology patients and their parents can reliably report
      their own perceived built environment satisfaction, which is significantly
      related to the quality of the objective built environment. For parents, results
      support the mediational hypothesis, highlighting the importance that perceived
      built environment satisfaction plays in psychosocial functioning and healthcare
      satisfaction.

PMID- 21960192
TI  - Evaluation of the built environment: staff and family satisfaction pre- and post
      occupancy of the Children's Hospital.
AB  - OBJECTIVE: To evaluate and compare the impact of an existing and newly built
      hospital environment on family and staff satisfaction related to light, noise,
      temperature, aesthetics, and amenities, as well as safety, security, and privacy.
      BACKGROUND: The United States is engaged in an unprecedented healthcare building
      boom driven by the need to replace aging facilities, understand the impact of the
      built environment on quality and safety, incorporate rapidly emerging
      technologies, and enhance patient- and family-centered care. More importantly,
      there is heightened attention to creating optimal physical environments to
      achieve the best possible outcomes for patients, families, and staff. METHODS:
      Using a pre-post descriptive survey design, all nursing, social work, therapy
      staff, and families on selected inpatient units were invited to participate. A
      demographic form and Family and Staff Satisfaction Surveys were developed and
      administered pre- and post-occupancy of the new facility. RESULTS: Pre/post mean
      scores for staff satisfaction improved on all survey subscales with statistically
      significant improvement (p < .05) in most areas. The most improvement was seen
      with layout of the patient room, natural light, storage and writing surfaces, and
      comfort and appeal. Family satisfaction demonstrated statistically significant
      improvement on all subscales (p <= .01), especially for natural light, quiet
      space, parking, and the child's room as a healing environment. CONCLUSIONS:
      Families and staff reported greater satisfaction with the newly built hospital
      environment compared to the old facility. Study results will help guide future
      architectural design decisions, attract and retain staff at a world-class
      facility, and create the most effective healing environments.

PMID- 21960193
TI  - Color-coding and human factors engineering to improve patient safety
      characteristics of paper-based emergency department clinical documentation.
AB  - OBJECTIVE: Investigators studied an emergency department (ED) physical chart
      system and identified inconsistent, small font labeling; a single-color scheme;
      and an absence of human factors engineering (HFE) cues. A case study and
      description of the methodology with which surrogate measures of chart-related
      patient safety were studied and subsequently used to reduce latent hazards are
      presented. BACKGROUND: Medical records present a challenge to patient safety in
      EDs. Application of HFE can improve specific aspects of existing medical chart
      organization systems as they pertain to patient safety in acute care
      environments. METHODS: During 10 random audits over 5 consecutive days (573 data
      points), 56 (9.8%) chart binders (range 0.0-23%) were found to be either
      misplaced or improperly positioned relative to other chart binders; 12 (21%) were
      in the critical care area. HFE principles were applied to develop an experimental
      chart binder system with alternating color-based chart groupings, simple and
      prominent identifiers, and embedded visual cues. RESULTS: Post-intervention
      audits revealed significant reductions in chart binder location problems overall
      (p < 0.01), for Urgent Care A and B pods (6.4% to 1.2%; p < 0.05), Fast Track C
      pod (19.3% to 0.0%; p < 0.05) and Behavioral/Substance Abuse D pod (15.7% to
      0.0%; p < 0.05) areas of the ED. The critical care room area did not display an
      improvement (11.4% to 13.2%; p = 0.40). CONCLUSIONS: Application of HFE methods
      may aid the development, assessment, and modification of acute care clinical
      environments through evidence-based design methodologies and contribute to safe
      patient care delivery.

PMID- 21960194
TI  - Flexibility: beyond the buzzword-practical findings from a systematic literature
      review.
AB  - OBJECTIVE: The goal was to identify practical, cost-effective, design-related
      strategies for "future-proofing" the buildings of a major Australian health
      department. BACKGROUND: Many health buildings become obsolete before the end of
      their effective physical lives, requiring extensive reconfiguration or
      replacement. This study sought to move beyond the oft-used buzzword flexibility
      to seek effective strategies to accommodate future change (future-proofing) that
      could be further explored in Australia and other developed countries. METHODS: A
      systematic literature review compiled definitions of flexibility and adaptability
      from a range of sources. Nineteen case studies were identified that illustrated
      various future-proofing strategies. A matrix was developed to classify different
      approaches to flexibility and then used to assess the case studies. RESULTS:
      Analysis was hampered by inconsistent use of terminology and limited availability
      of quantifiable methods for assessing the long-term success of approaches to
      future-proofing. Several key strategies were identified, classified, and
      discussed in terms of their relevance and application. CONCLUSIONS: More rigorous
      definitions of flexibility, adaptability, and related terms are needed to enable
      more useful comparisons of the strategies implemented to future-proof health
      projects. Local conditions often affect both the strategies adopted and the
      degree to which they can be considered successful. Many of the case studies
      analyzed in this research were not operational long enough to enable assessment
      of their claims of being future-proofed. Therefore, review of lifetime facility
      costs, including the service life periods of major facility components, should be
      considered, and some older projects should be evaluated in terms of these
      criteria.

PMID- 21960195
TI  - Flexibility, differential obsolescence, and measurement.

PMID- 21960196
TI  - Integrated healthscape strategies: an ecological approach to evidence-based
      design.
AB  - AIM: This paper explores some of the premises of evidence-based design (EBD) and
      suggests that greater attention to and differentiation of the various purposes of
      research are needed, along with the development of an ecological theory that
      reflects the complexity of the health systems studied and more varied ways to
      communicate with and engage practitioners. BACKGROUND: Problems with the American
      healthcare system are well known. For the past 20 years, an intervention that has
      gained increasing attention has been the physical design of healthcare facilities
      hospitals in particular. EBD has been advocated as one means of using research to
      examine the relationship between design and healthcare to improve patient safety
      and the quality of care. CONCLUSIONS: The concept of integrated healthscape
      strategies is proposed to focus not only on research "evidence" and the methods
      used to collect and analyze it, but also on the different purposes research
      serves, the role of theory, and the use of EBD research in practice.

PMID- 21960197
TI  - Hospitals on the time axis: trends in the real world and implications for
      architectural education.
AB  - Hospitals are never finished, and in the best cases they retain value and
      coherence for decades while they adjust in response to the dynamics of the
      healthcare field. In the worst cases, the facility is demolished, incapable of
      accommodating cycles of change. These are well known but poorly documented
      realities. Today, it is not unusual for one architect to design a hospital and
      another to design the interior fit-out, either initially or years later. Some
      clients ask for "shell space" to be fitted out later by another firm. Architects
      educated to define function first and to maintain unified control find this
      unsettling, believing that only if one party controls everything can high-quality
      architecture result. This is not the case, as diverse buildings, cities, and
      neighborhoods show, but the belief dies hard. In fact, the educational paradigm
      in schools of architecture largely maintains the old myths.This article describes
      this reality and poses questions about habit and method that are now at odds with
      reality. Finally, the paper suggests a way to handle new realities in the
      education of the next generation of architects.

PMID- 21960198
TI  - Understanding evidence-based research methods: pilot testing surveys.

PMID- 21960199
TI  - Letter to the editors. Healthcare facility design projects.

PMID- 21960202
TI  - Clinical outcomes of laparo-endoscopic single-site surgery radical nephrectomy.
AB  - INTRODUCTION: The conventional laparoscopic surgery is now paving way to the new
      technologies including robotic and laparoscopic single-site surgery (LESS). We
      present our updated experience on LESS radical nephrectomy (LESS-RN). PATIENTS
      AND METHODS: The data from patients undergoing LESS-RN in our two institutions
      were reviewed along with various clinical and pathological parameters. RESULTS:
      Between 2008 and 2011, 42 LESS-RN were performed (right = 22, left = 20) with
      mean (range) age and BMI of 63.7 (33-86) years and 25.1 (18-38.6) kg/m(2),
      respectively. In addition to the instruments in the single port, one extra 3-mm
      needlescopic instrument was required in 19 patients (right = 17, left = 2). In
      three patients, two additional 5-mm trocars and instruments were required. None
      required open conversion. The recorded adverse events include one bowel injury
      (intraoperative closure without the need for stoma), one postoperative bleeding
      requiring blood transfusion, one prolonged ileus, and one deep venous thrombosis.
      The resected specimens revealed pT1a (n = 3), pT1b (n = 33), pT2a (n = 4), and
      pT3b (n = 2) tumors. The finding of pT3b was incidental rather than planned
      procedure. None of the patients had positive margins. CONCLUSION: LESS-RN has
      proven to be feasible and safe. Beyond cosmesis, further advantages of this
      approach need to be addressed by randomized trials.

PMID- 21960204
TI  - dc Electrokinetics for spherical particles in salt-free concentrated suspensions
      including ion size effects.
AB  - We study the electrophoretic mobility of spherical particles and the electrical
      conductivity in salt-free concentrated suspensions including finite ion size
      effects. An ideal salt-free suspension is composed of just charged colloidal
      particles and the added counterions that counterbalance their surface charge. In
      a very recent paper [Roa et al., Phys. Chem. Chem. Phys., 2011, 13, 3960-3968] we
      presented a model for the equilibrium electric double layer for this kind of
      suspensions considering the size of the counterions, and now we extend this work
      to analyze the response of the suspension under a static external electric field.
      The numerical results show the high importance of such corrections for moderate
      to high particle charges, especially when a region of closest approach of the
      counterions to the particle surface is considered. The present work sets the
      basis for further theoretical models with finite ion size corrections, concerning
      particularly the ac electrokinetics and rheology of such systems.

PMID- 21960205
TI  - "I" and the brain.
AB  - Many philosophers as well as many biological psychologists think that recent
      experiments in neuropsychology have definitively discredited any notion of
      freedom of the will. I argue that the arguments mounted against the concept of
      freedom of the will in the name of natural causal determinism are valuable but
      not new, and that they leave intact a concept of freedom of the will that is
      compatible with causal determinism. After explaining this concept, I argue that
      it is interestingly related to our use of the first person pronoun "I." I discuss
      three examples of our use of "I" in thought and language and submit a few
      questions I would like neuropsychologists to answer concerning the brain
      processes that might underlie those uses. I suggest answering these questions
      would support the compatibilist notion of freedom of the will I have offered in
      part 1.

PMID- 21960203
TI  - Atypical development of resting respiratory sinus arrhythmia in children at high
      risk for depression.
AB  - Compromised respiratory sinus arrhythmia (RSA, i.e., low cardiac vagal control)
      frequently characterizes clinically depressed adults and also has been detected
      in infants of depressed mothers; however, its existence has not been established
      in older at-risk offspring. We investigated developmental patterns of RSA in a
      sample of 163 5- to 14-year-old children, who were either at high risk for
      depression (due to having a parent with a childhood-onset mood disorder) or low
      risk for depression. We hypothesized that high-risk children have lower resting
      RSA than do low-risk children, which could reflect atypical developmental
      trajectories. Children's RSA was assessed during resting baseline periods on
      multiple occasions, typically 1-year apart. Linear growth modeling indicated a
      group by age interaction. Low-risk children (but not the high-risk children)
      exhibited a significantly increasing trajectory in resting RSA with age. Mood
      disorders in offspring did not account for the Group X Age interaction effect.
      Our study provides new evidence that children at high risk for depression have an
      atypical developmental trajectory of RSA across late childhood.

PMID- 21960206
TI  - Microwave-assisted synthesis of CdS-reduced graphene oxide composites for
      photocatalytic reduction of Cr(VI).
AB  - CdS-reduced graphene oxide (RGO) composites are successfully synthesized via the
      microwave-assisted reduction of graphite oxide in a CdS precursor solution using
      a microwave synthesis system. The photocatalytic performances of CdS-RGO
      composites in the reduction of Cr(VI) are investigated. The results show that CdS
      RGO composites exhibit enhanced photocatalytic performance for the reduction of
      Cr(VI) with a maximum removal rate of 92% under visible light irradiation as
      compared with pure CdS (79%) due to the increased light absorption intensity and
      the reduction of electron-hole pair recombination in CdS with the introduction of
      RGO.

PMID- 21960207
TI  - Multidisciplinary management of malignant pleural effusion.
AB  - Approximately 50% of patients with metastatic disease develop a malignant pleural
      effusion (MPE). Prompt clinical evaluation and treatment to achieve successful
      palliation are the main goals of management of MPE. Optimal treatment is still
      controversial and there is no universal standard approach. Management options
      include observation, thoracentesis, indwelling pleural catheter (IPC) or chest
      tube placement, pleurodesis, and surgical pleurectomy. The treatment for each
      patient should be based on symptoms, general condition, and life expectancy.

PMID- 21960208
TI  - Computed tomography diagnosis of myocardial infarction in a patient with normal
      initial cardiac biomarkers.

PMID- 21960209
TI  - Selective hydroformylation-hydrogenation tandem reaction of isoprene to 3
      methylpentanal.
AB  - The hydroformylation of isoprene catalysed by rhodium phosphine complexes usually
      yields a broad mixture of the monoaldehydes, the isomeric methylpentenals, as
      well as the dialdehyde 3-methyl-1,6-hexandial. Under usual reaction conditions
      the products of a consecutive hydrogenation are only formed as minor by-products.
      Surprisingly we discovered now a selective auto-tandem reaction consisting of a
      hydroformylation and a hydrogenation step if a rhodium complex with the chelate
      ligand bis(diphenylphosphino)ethane is used as catalyst. If branched aromatic
      solvents like cumene are applied the conversion of isoprene is nearly
      quantitatively and the yield of the tandem product 3-methylpentanal amounts to
      85%.

PMID- 21960210
TI  - Acromegaly due to an ectopic pituitary adenoma in the clivus: case report and
      review of literature.
AB  - Pituitary adenomas rarely originate outside the sella turcica. Ectopic locations
      include the suprasellar region, sphenoid sinus, cavernous sinus and clivus. We
      describe a 50-year-old female who presented with clinical signs and biochemical
      evidence of acromegaly. Pituitary MRI demonstrated a 2 mm hypointense lesion on
      the right side of the pituitary gland. However upon drilling of the upper clival
      bone to expose the sella during endoscopic transsphenoidal surgery, soft tumor
      like tissue was encountered within the clivus. Exploration of the sella,
      including the area of hypointensity noted on preoperative imaging, did not
      identify any other abnormality. Immunohistochemical examination of the fully
      resected tumor demonstrated growth hormone immunoreactivity. Failed preoperative
      diagnosis of this rare ectopic GH-producing tumor was compounded by the presence
      of a misleading pituitary abnormality consistent with a microadenoma. The
      epidemiology and pertinent literature of this uncommon condition is discussed.

PMID- 21960212
TI  - Targeting cancer with small-molecular-weight kinase inhibitors.
AB  - Protein and lipid kinases fulfill essential roles in many signaling pathways that
      regulate normal cell functions. Deregulation of these kinase activities lead to a
      variety of pathologies ranging from cancer to inflammatory diseases, diabetes,
      infectious diseases, cardiovascular disorders, cell growth and survival. 518
      protein kinases and about 20 lipid-modifying kinases are encoded by the human
      genome, and a much larger proportion of additional kinases are present in
      parasite, bacterial, fungal, and viral genomes that are susceptible to
      exploitation as drug targets. Since many human diseases result from
      overactivation of protein and lipid kinases due to mutations and/or
      overexpression, this enzyme class represents an important target for the
      pharmaceutical industry. Approximately one third of all protein targets under
      investigation in the pharmaceutical industry are protein or lipid kinases.The
      kinase inhibitors that have been launched, thus far, are mainly in oncology
      indications and are directed against a handful of protein and lipid kinases. With
      one exception, all of these registered kinase inhibitors are directed toward the
      ATP-site and display different selectivities, potencies, and pharmacokinetic
      properties. At present, about 150 kinase-targeted drugs are in clinical
      development and many more in various stages of preclinical development. Kinase
      inhibitor drugs that are in clinical trials target all stages of signal
      transduction from the receptor protein tyrosine kinases that initiate
      intracellular signaling, through second-messenger-dependent lipid and protein
      kinases, and protein kinases that regulate the cell cycle.This review provides an
      insight into protein and lipid kinase drug discovery with respect to
      achievements, binding modes of inhibitors, and novel avenues for the generation
      of second-generation kinase inhibitors to treat cancers.

PMID- 21960211
TI  - Comparison of two immunoassays in the determination of IGF-I levels and its
      correlation with oral glucose tolerance test (OGTT) and with clinical symptoms in
      acromegalic patients.
AB  - The aim of our study was to evaluate two different methodologies in IGF-I levels
      determination, its correlation with GH nadir in OGTT <1 and <0.4 ng/ml and with
      clinical symptoms in acromegalic patients. We analyzed 37 patients. Sixteen
      patients had not undergone any kind of treatment (Group 1). Twenty-one patients
      underwent surgery as primary treatment, and after that, some of them another kind
      of treatment (except pegvisomant) (Group 2). Serum IGF-I levels were measured by
      Immulite-1000 (IMM) and by an immunoradiometric assay (DSL) and, GH by
      immunochemiluminometric assay. IGF-I levels by IMM and by DSL showed a
      significant difference. When we analyzed in both groups the concordance by
      crosstabs-Kappa coefficients, between different parameters, GH nadir <1 and <0.4
      ng/ml with IGF-I by DSL and IMM showed concordance in group 1, but in group 2
      only GH nadir <1 and <0.4 ng/ml had a weak concordance with IGF-I by IMM. When we
      analyzed clinical symptoms in the patients and, GH nadir <1 and <0.4 ng/ml and
      IGF-I levels by both methodologies, more than 90% of clinically active patients
      had abnormal GH response or/and elevated IGF-I levels in group 1, but less than
      70% in group 2. In the 8 patients under medical treatment, GH nadir was higher
      than 0.4 ng/ml in all patients, and IGF-I levels were elevated in 8/8 by DSL and
      in 6/8 by IMM. In conclusion, discrepant GH and IGF-I levels in the diagnosis and
      follow-up of patients with acromegaly requires consideration of many factors that
      influence these parameters.

PMID- 21960213
TI  - Small-molecule protein and lipid kinase inhibitors in inflammation and specific
      models for their evaluation.
AB  - The inflammatory response requires complex and coordinated cooperation of
      different signaling pathways and cell types. Therefore, more than 40 different
      protein or lipid kinases can be regarded as potential small-molecule inhibitor
      targets to approach a therapy of acute inflammation, such as septic syndrome, and
      especially chronic inflammation, such as rheumatoid arthritis or inflammatory
      bowel disease. Besides the general considerations about selectivity and potency
      of small-molecule kinase inhibitors, in this chapter special emphasis is put on
      the inflammation-specific methods and assays available for testing potential
      small-molecule inhibitors for their anti-inflammatory activity. Examples for
      human cell-based assays for characterization of the effect of inhibitors on
      contribution of various cell types, such as monocytes, neutrophils, mast cells, T
      cells, and synovial fibroblasts, to the inflammatory scenario are given. It is
      further demonstrated how these assays are complemented by rodent models for
      septic syndrome, rheumatoid arthritis, ulcerative colitis, Crohn's disease, and
      systemic lupus erythematosus. Finally, it is discussed how the results obtained
      by these methods can be further validated and which future strategies for the
      treatment of chronic inflammation will exist.

PMID- 21960214
TI  - Measuring the activity of leucine-rich repeat kinase 2: a kinase involved in
      Parkinson's disease.
AB  - Mutations in the LRRK2 (Leucine-Rich Repeat Kinase 2) gene are the most common
      cause of autosomal dominant Parkinson's disease. LRRK2 has multiple functional
      domains including a kinase domain. The kinase activity of LRRK2 is implicated in
      the pathogenesis of Parkinson's disease. Developing an assay to understand the
      mechanisms of LRRK2 kinase activity is important for the development of
      pharmacologic and therapeutic applications. Here, we describe how to measure in
      vitro LRRK2 kinase activity and its inhibition.

PMID- 21960215
TI  - Measuring PI3K lipid kinase activity.
AB  - Class IA phosphoinositide-3 kinases (PI3Ks) signaling has recently emerged as a
      key element in cancer development because of its ability to trigger a complex
      panoply of cellular responses controlling survival and proliferation. Many
      cancers show inappropriately activated PI3K pathway, and tumors with high PI3K
      activity are frequently resistant to traditional chemotherapy. Indeed,
      preclinical studies demonstrated a prominent role for the PI3K pathway in cancer
      cell survival and growth, thus validating PI3K as a potential drug target in
      cancer. The emerging interest in inhibiting PI3Ks in cancer have prompted the
      aggressive development of new selective PI3K pathway inhibitors as cancer
      therapy, and many of these molecules are currently in early-phase clinical
      trials. In this chapter, we describe methods to measure the PI3K lipid kinase
      activity in vitro, which is the standard procedure to test the efficacy of
      inhibitors.

PMID- 21960216
TI  - A fluorescence polarization assay for the discovery of inhibitors of the polo-box
      domain of polo-like kinase 1.
AB  - Polo-like kinase 1 (Plk1) is a key player in mitosis and has been widely
      recognized as a therapeutic target for many human cancer types. Apart from its
      kinase domain, Plk1 harbors a protein-protein interaction domain dubbed "polo-box
      domain" (PBD), by which the enzyme binds to its intracellular anchorage sites and
      to at least a fraction of its substrates. Recent evidence indicates that the
      inhibition of the PBD by small molecules is feasible and might allow for the
      discovery of highly specific inhibitors of the enzyme. This chapter details the
      practical work necessary to set up an assay based on fluorescence polarization
      for the discovery of inhibitors of the Plk1 PBD, which can be used for high
      throughput screening in a 384-well format.

PMID- 21960217
TI  - Assessment of hepatotoxicity potential of drug candidate molecules including
      kinase inhibitors by hepatocyte imaging assay technology and bile flux imaging
      assay technology.
AB  - Kinases are members of a major protein family targeted for drug discovery and
      development. Given the ubiquitous nature of many kinases as well as the broad
      range of pathways controlled by these enzymes, early safety assessments of small
      molecule inhibitors of kinases are crucial in identifying new molecules with
      sufficient therapeutic window for clinical development. Failure or attrition of
      drug candidates in late-stage pipelines due to hepatotoxicity is a significant
      challenge in the drug development field. Herein we provide detailed methods for
      the hepatocyte imaging assay technology (HIAT) and the bile flux imaging assay
      technology (BIAT) to evaluate drug-induced liver injury (DILI) potentials for
      drug candidates. Optimized culturing methods for primary human hepatocytes, both
      freshly isolated and prequalified cryopreserved cells, are also presented. The
      applications of these high-content cellular imaging technologies in the
      evaluation of p38 and Her2 kinase inhibitors are highlighted to illustrate the
      usefulness of the research methodology in a compound screening as well as
      mechanistic investigative setting.

PMID- 21960218
TI  - Kinase inhibitor selectivity profiling using differential scanning fluorimetry.
AB  - Fast, robust, and inexpensive screening methods are the heart of drug discovery
      processes. Moreover, it is useful to have access to several established assay
      formats, for validation purposes. If a targeted protein is an enzyme, the logical
      and widely used approach is the direct measurement of the effect of the added
      ligands on its activity. A variety of enzymatic assay formats have been
      successfully applied for inhibitor screening of protein kinases. However,
      enzymatic assays require an active enzyme with a known substrate and often time
      consuming assay optimization. Several alternative approaches have been recently
      developed that detect binding of ligands to proteins. This chapter overviews and
      provides the experimental protocol of the successful application of differential
      scanning fluorimetry (DSF) in our laboratory for fast and robust screening of
      medium-sized (<10,000) inhibitor libraries. DSF monitors the thermal
      stabilization of the native protein structure upon ligand binding. It allows
      selectivity profiling of any protein kinase without prior knowledge of either
      substrate or activity of the kinase under investigation. Comparative studies
      revealed that generated data is highly reproducible and correlates well with the
      results from other ligand binding methodologies, direct binding constants as well
      as enzymatic assays.

PMID- 21960219
TI  - Chemoproteomic characterization of protein kinase inhibitors using immobilized
      ATP.
AB  - Protein kinase inhibitors have emerged as indispensable tools for the elucidation
      of the biological functions of specific signal transduction pathways and as
      promising candidates for molecular-targeted therapy. However, because many
      protein kinase inhibitors are ATP-competitive inhibitors targeting the catalytic
      site of specific protein kinases, the large number of protein kinases that are
      encoded within eukaryotic genomes and the existence of many other cellular
      proteins that bind ATP result in the prospect of off-target effects for many of
      these compounds. Many of the potential off-target effects remain unrecognized
      because protein kinase inhibitors are often developed and tested primarily on the
      basis of in vitro assays using purified components. To overcome this limitation,
      we describe a systematic approach to characterize ATP-competitive protein kinase
      inhibitors employing ATP-sepharose to capture the purine-binding proteome from
      cell extracts. Protein kinase inhibitors can be used in competition experiments
      to prevent binding of specific cellular proteins to ATP-sepharose or to elute
      bound proteins from ATP-sepharose. Collectively, these strategies can enable
      validation of interactions between a specific protein kinase and an inhibitor in
      complex mixtures and can yield the identification of inhibitor targets.

PMID- 21960220
TI  - Proteome-wide identification of staurosporine-binding kinases using capture
      compound mass spectrometry.
AB  - The enormous diversity of kinases and their pivotal role in cell signaling have
      set kinases in the focus of biomedical research. Profiling the kinome of tissues
      of different origin is essential for biomarker discovery. In drug research, it is
      necessary to comprehend the specificity profile of a given kinase inhibitor.
      Capture Compound Mass Spectrometry (CCMS) (Koster et al., Assay Drug. Dev.
      Technol. 5:381-390, 2007) addresses the need for a tool to physically isolate and
      reliably profile the binders of kinase inhibitors directly in biological samples.
      Capture CompoundsTM are trifunctional probes: a selectivity function consisting
      of the kinase inhibitor interacts reversibly with the native target proteins in
      equilibrium, a photoactivatable reactivity function forms an irreversible
      covalent bond to the target protein upon irradiation, and a sorting function
      allows the captured protein(s) to be isolated and identified by mass
      spectrometric analysis in an affinity-driven manner. Capture CompoundsTM with any
      kinase inhibitor as selectivity function can be synthesized. We here used
      staurosporine as the selectivity function because it targets and, therefore,
      allows profiling a broad range of kinases (Romano and Giordano, Cell Cycle 7:3364
      3668, 2008). Furthermore, we give an example of the application of the
      staurosporine Capture Compound to isolate kinases from human liver-derived HepG2
      cells.

PMID- 21960221
TI  - Affinity purification of proteins binding to kinase inhibitors immobilized on
      self-assembling monolayers.
AB  - Kinase inhibitors represent a relatively new class of drugs that offer novel
      therapies targeting specific -malfunctioning kinase-mediated signaling pathways
      in oncology and potentially inflammation. As the ATP binding sites of the ~500
      human kinases are structurally conserved and because most current drugs target
      the ATP binding site, there is a need to profile all the kinases that a drug may
      bind and/or inhibit. We have developed a chemical proteomics method that affinity
      purifies kinases from cell or tissue lysates using kinase inhibitors immobilized
      on self-assembling monolayers. The method can be applied to assess the
      selectivity of a given kinase inhibitor and thus to guide its preclinical or
      clinical development.

PMID- 21960222
TI  - Kinase inhibitor profiling using chemoproteomics.
AB  - Quantitative chemoproteomics has recently emerged as an experimental approach to
      determine protein interaction profiles of small molecules in a given cell line or
      tissue. In contrast to standard biochemical and biophysical kinase assays,
      application of this method to kinase inhibitors determines compound binding to
      endogenously expressed kinases under conditions approximating the physiological
      situation with regard to the molecular state of the kinase and presence of
      required cofactors and regulatory proteins. Using a dose-dependent, competition
      based experimental design in combination with quantitative mass spectrometry
      approaches, such as the use of tandem mass tags (TMT) for isobaric labeling
      described here, allows to rank-order interactions of inhibitors to kinase by
      binding affinity.

PMID- 21960223
TI  - Covalent cross-linking of kinases with their corresponding peptide substrates.
AB  - Protein phosphorylation represents the most dominant and evolutionary conserved
      posttranslational modification for information transfer in cells and organisms.
      The human genome encodes >500 protein kinases, and thousands of phosphorylation
      sites are present in mammalian proteome. To develop a global view of
      phosphorylation network, there is a need to map the connectivity between kinases
      and phosphoproteome. We developed a chemical kinase-substrate cross-linker 1 that
      converts transient kinase-substrate interactions into a covalently linked kinase
      substrate complex in vitro and in the presence of cell lysates. The method can be
      applied to identify unknown upstream kinases responsible for phosphorylation
      events in cell lysates.

PMID- 21960224
TI  - Receptor tyrosine kinase inhibitor profiling using bead-based multiplex sandwich
      immunoassays.
AB  - Receptor tyrosine kinases (RTK) are important targets in drug discovery
      processes. Studying the phosphorylation pattern of RTKs enables the determination
      of their activation and inactivation states. Multiplex bead-based sandwich
      immunoassays are powerful tools for measuring the phosphorylation state of key
      regulators within cellular signalling networks. Here, we describe the analysis of
      the phosphorylation state of receptor tyrosine kinases using the epidermal growth
      factor receptor (EGFR) as an example. We provide a protocol for a bead-based
      sandwich immunoassay that enables a relative quantification of the EGFR and its
      generic tyrosine phosphorylation. We also present data from a kinase inhibitor
      experiment using 96-well cell-culture plates and a commercially available kit for
      the analysis of seven receptor tyrosine kinases.

PMID- 21960225
TI  - Monitoring phosphoproteomic response to targeted kinase inhibitors using reverse
      phase protein microarrays.
AB  - Phosphoproteomic networks mediated by protein kinases are the key drivers of
      proliferative and survival signals underlying human cancers, and as such a number
      of kinases have been the subject of intensive drug discovery efforts. A key
      question that must be answered during clinical development is whether a kinase
      inhibitor is effectively inhibiting its appropriate target kinase and pathway in
      the tumor. Reverse-phase protein arrays (RPMAs) offer the ability to analyze
      behavior of entire signaling networks in response to drug treatment and thus have
      promise as a technology for monitoring cellular response to kinase inhibitors. We
      have shown that it is possible to use RPMAs to detect phosphorylation changes in
      key multiple signaling pathway proteins in response to targeted inhibitors of
      EGFR, MEK, and PI3 kinase.

PMID- 21960226
TI  - Measuring phosphorylation-specific changes in response to kinase inhibitors in
      mammalian cells using quantitative proteomics.
AB  - Many cancers have been associated with the deregulation of kinases, and thus,
      kinases have become a prime target for the development of cancer treatments. This
      focus on kinases has resulted in the approval of several small-molecule kinase
      inhibitors for cancer treatments. Further, the use of these inhibitors as tools
      to study cancer has provided valuable information about biological mechanisms.
      However, to date, not much is known about the global effects of kinases on the
      proteome or phosphoproteome. In this protocol, we describe methodology to study
      the impact of kinase inhibitors on the proteome and phosphoproteome using mass
      spectrometry-based quantitative proteomics. More specifically, we focus on the
      effects of Aurora B kinase inhibitors on the proteome, cytoskeleton proteome, the
      phosphoproteome, and the cytoskeleton phosphoproteome during cell cycle. This
      methodology is easily extended to other biological studies whose aim is to study
      the global proteomic effects of a kinase inhibitor.

PMID- 21960227
TI  - Investigation of acquired resistance to EGFR-targeted therapies in lung cancer
      using cDNA microarrays.
AB  - Clinical tools to accurately describe, evaluate, and predict an individual's
      response to cancer therapy are a field-wide priority; in many advanced cancers,
      only 10-20% of individuals will have a clinical benefit from therapy, yet we
      treat the entire population. Furthermore, many therapies are initially effective,
      but lose effectiveness over time. Here we describe methods to derive in vitro
      models of resistance to EGFR tyrosine kinase inhibitors. We additionally describe
      approaches to characterize possible mechanisms of resistance by genomic and
      transcriptomic approaches.

PMID- 21960228
TI  - [Epidemiology of urolithiasis].
AB  - Recently, urolithiasis is increasing in the world. The onset of urolithiasis is
      considered to associate with high protein and fat dietary habits. In the
      articles, using epidemiological method and research, the prevalence and incidence
      of the upper urinary tract stones as kidney and ureter is described. In addition,
      the association between dietary intake and calcium metabolism is reviewed.

PMID- 21960229
TI  - [Diagnosis and treatment of urolithiasis with primary hyperparathyroidism].
AB  - Primary hyperparathyroidism (PHPT) is a disease to cause calcium, phosphorus,
      bone metabolism abnormality by the over secretion of parathyroid hormone (PTH) .
      A rise of PTH brings hypercalcemia, hypophosphatemia, and clinical symptoms
      include a recurrent urolithiasis, a letter of psychoneurosis, a gastrointestinal
      ulcer and bone resorption. It is the object disease of the clinical study that is
      important as one of the causes of urolithiasis in the urology department domain
      now because most of symptom type PHPT is renal stone types although it is a
      border domain with the internal secretion surgery, and the disease is often
      discovered at the urology department.

PMID- 21960230
TI  - [Clinical strategies for prevention of drug-induced urinary calculi].
AB  - Drug-induced urinary calculi, although they account for only 1-2% of urinary
      calculi, deserve consideration because most of them are preventable. In the drug
      containing calculi resulting from the crystallization of a certain drug and its
      metabolites in the urine, stone analysis can identify the responsible drug.
      While, in the drug-induced metabolic calculi caused by interference with calcium,
      oxalate and purine metabolism, careful clinical inquiry is necessary to reveal
      involvement of a certain drug in stone formation. Better awareness of the
      possible drugs with lithogenic potential and close surveillance of patients on
      long-term treatment with these drugs are necessary. Especially, in patients with
      a history of urolithiaisis, prescription of lithogenic drugs deserve careful
      consideration.

PMID- 21960231
TI  - [Renal calcium excretion and urolithiasis].
AB  - Patients with urolithiasis have been increasing in the world, especially
      morbidity of calcium nephrolithiasis has been increasing in the advanced
      countries. The changes in the environmental factors including alternation of diet
      are said to be associated with the increment of morbidity of kidney stone.
      Idiopathic hypercalciuria is one of the most important risk factor of calcium
      nephrolithiasis and is classified into absorptive, resorptive, and renal leak.
      Though the origins of these three types of hypercalciuria are different,
      increased bone resorption and increased calcium absorption from gut tend to be
      observed simultaneously. Not only genetic abnormalities in the proteins which are
      involved in calcium metabolisms but environmental factors such as high sodium
      intake and chronic acid load caused by increased ingestion of animal protein have
      been considered to be associated with increased urinary calcium excretion. Renal
      metabolisms of oxalate and phosphate which are important compositions of calcium
      containing stone, uric acid as a promoter and citrate as a inhibitor of
      nephrolithiasis are also described.

PMID- 21960232
TI  - [Gene expression and its role on urolithiasis].
AB  - Kidney stone disease is a common condition, affecting up to 10% of the population
      in Japan as well as in the industrial world. Calcium oxalate is major stone
      composition, consists of crystal and stone matrix, and arises from a combination
      of environmental and genetic factors.  To date, considerable progress has been
      made identifying the metabolic risk factors predisposing to this complex disease.
      The familial association of calcium oxalate stone has been corroborated by
      numerous studies. The specific genetic and epigenetic factors have remained less
      clear. However genetic variations have indicated using single nucleotide
      polymorphism (SNP) , and recent technological advances by way of commercially
      available SNP array or chips, which capture common human variation across the
      entire genome, have been revolutionizing the study and identifying a new gene as
      a risk locus in idiopathic calcium oxalate kidney stone disease.

PMID- 21960233
TI  - [Molecular mechanism of renal stone formation].
AB  - Urolithiasis is a multifactorial disease involving environmental and gentic
      factors. Calcium-containing stones, which are>90% of all stones, detected most
      frequently ; however, radically effective prevention and detailed investigation
      of crystal formation have not been established. Renal stone formation is a
      complex multistep process that includes supersaturation, crystal nucleation,
      growth, and aggregation. In the early stage of crystal formation, exposure to
      high concentrations of oxalate can induce renal tubular cell injury, following
      crystal attachment to renal tubular cell in which stone matrix proteins or
      urinary high molecular substances play an important role as a promoter or
      inhibitor respectively. Recent study speculated that renal macrophage could
      englobe crystals and might digest them. In this part, we propose the molecular
      mechanism that has been newly investigated recently, in renal stone formation.

PMID- 21960234
TI  - [Relationship between metabolic syndrome and urinary stone disease].
AB  - Epidemiologically, there are many same characteristics among patients with
      urolithiasis, life-style related diseases and metabolic syndrome. In a comparison
      with the major urological diseases, the patients with stone disease have the
      largest amount of visceral fat on computerized tomography. The patients who
      finally had a diagnosis of metabolic syndrome in urolithiasis were 43% of men and
      female 31%. The clinical features of the patients include increased urinary
      oxalate excretion, abnormal uric acid metabolism, and acidic urine. The basic
      studies by the animal experiments suggest that there is a close relationship
      between urolithiasis and metabolic syndrome. After the treatment of the urinary
      stone, it is very important to make a long-term follow-up by not only the
      prevention of recurrent stone episode but also life style management and medical
      treatment for metabolic syndrome.

PMID- 21960235
TI  - [Vital relationship between osteopontin and urolothiasis].
AB  - Urological rediscovery of osteopontin (OPN) in 1992 has opened a new era in the
      understanding of mechanisms in development of urolithiasis over the two decades.
      OPN had the multiple functions, and it was difficult to understand the overall
      role. It has been understood that OPN is a promoting agent for urolithiasis
      development in the issue as a result of a lot of experiments. And it became clear
      that OPN having received the control of free radicals from NADPH oxidase and
      angiotensin II . The clinical application that uses OPN antibody and/or ARB for
      preventing urolithiasis is expected. I describe the vital role of OPN in
      development of urolithiasis in this paragraph.

PMID- 21960236
TI  - [Kidney stone formation during space flight and long-term bed rest].
AB  - Microgravity environment like space flight or a condition requiring long-term bed
      rest increase bone resorption and decrease bone formation, inducing the rapid
      decrease of bone minerals to osteoporosis. Bone mineral loss increases urinary
      calcium excretion and the risk of urinary stone formation. To clarify the
      influence of the conditions on renal stone formation, a 90-day bed rest test was
      performed to analyze the mechanism of microgravity or bed rest-induced stone
      formation and prevention by bisphosphonate medication and bed-rest exercise. As
      the results, renal stone formation was observed in control and exercise groups
      and no stone was seen in the medication group. In the medication group, urinary
      calcium excretion and relative supersaturation of calcium oxalate were lower than
      in the control group throughout the bed-rest and recovery period. Bisphosphonate
      is useful for the prevention of renal stone formation during space flight and
      long-term bed-rest.

PMID- 21960237
TI  - [New therapy using bisphosphonate for urolithiasis].
AB  - Osteoporosis is characterized by a reduction in bone mineral density (BMD) .
      Reduced BMD has been reported in urolithiasis patients with hypercalciuria, as
      well as in those with normocalciuria. Bisphosphonates potently inhibit bone
      resorption and are used in the management of osteoporosis. We show the ability of
      bisphosphonate to prevent the recurrence of urolithiasis. Bisphosphonate reduced
      the excretion of urinary calcium and the ion activity product index of calcium
      phosphate in urolithiasis patients, and prevented urinary stone formation in long
      term bed rest test. The results suggest that ALN not only improves osteoporosis
      but also reduces the risk of calcium stone formation. Bisphosponates are believed
      to reduce the urinary excretion of calcium by improvement of bone metabolism, and
      to have a direct effect in the prevention of urolithiasis.

PMID- 21960238
TI  - [Medical expulsive therapy facilitated by alpha 1 adrenoceptor antagonist].
AB  - In 2002, speedy elimination of ureterolithiasis in the lower part of ureter was
      first reported with the alpha 1 blocker. Thereafter, there are a lot of reports
      including meta-analysis about tamsulosin. In 2011 EAU Guidelines on Urolithiasis,
      it is the most important to establish effective MET (medical expulsive therapy)
      to facilitate spontaneous stone passage. Alpha 1 blockers are the preferred
      agents for MET. As a basic evidence for MET, we reported that alpha 1a and 1d AR
      subtype mRNA was highly expressed in the human ureter and that alpha 1A AR is the
      main participant in the human ureteral contraction. It is published newly in
      Japanese Guidelines on Urolithiasis revised edition to schedule to be published
      soon.

PMID- 21960239
TI  - [Diet therapy and life guidance to prevent calcium stones].
AB  - Urolithiasis patients have a low continuation rate with regard to visiting the
      hospital and undergoing periodic check-ups following therapy. The increased
      Westernization of diets has played a major role in its onset, and it is believed
      to be a lifestyle disease. Therefore, the prevention of relapse is difficult
      without improving the patients' lifestyle and eating habits, and it has been
      defined as a disease with an extremely high relapse rate. On the other hand, it
      is believed that the opportunity for periodic visits to the hospital and check
      ups can be assured by continuously performing careful dietary interventions
      appropriate for each patient and by educating patients about the disease, thereby
      contributing to the prevention of relapses of urolithiasis.

PMID- 21960240
TI  - [Pharmacotherapy for preventing calcium containing stone formation].
AB  - Many urinary tract stones consist of calcium, and has high relapse rate.
      Accordingly, it is very important to prevent calcium-containing stone formation.
      This paper describes about effects and mechanisms for Xanthine oxidase inhibitor,
      citrate formulation, magnesium formulation, thiazides, vitamin B(6), extract of
      Quercus salicina Blume and chorei-to (medical herb) . Recent new drugs and the
      elucidation of new metabolic pathways may lead to the development of prevention
      of urolithiasis.

PMID- 21960241
TI  - [Surgical management for urolithiasis].
AB  - The indication of the surgical management for urolithiasis isn't decided only in
      the size of the stone. Even the small stone sometimes influences a kidney
      function and clinical symptom. Present Japanese surgical treatment for
      Urolithiasis is almost lithotripsy therapy. Though most of lithotripsy therapy is
      ESWL, TUL and PNL were chosen due to the state of the stone.

PMID- 21960242
TI  - [Calcium pros and cons: long term use of bisphosphonates. Bisphosphonates should
      be used for postmenopausal osteoporosis for a long term].
AB  - Only bisphosphonates have evidence that show to reduce the risk of vertebral,
      nonvertebral, and hip fractures in postmenopausal osteoporosis. From the
      viewpoint of risk benefit, it may be said that a utility is far superior to
      problems of the long-term use. Long-term use of bisphosphonates is necessary for
      the patients at elevated risk for the hip fracture.

PMID- 21960243
TI  - [Calcium pros and cons: long term use of bisphosphonates. Bisphophonate should
      not be used for long term].
AB  - It is ten years since bisphophonates have been used for osteoporosis treatment in
      Japan, while the number of long term bisphosphonate treatment patients has been
      increased. Recently atypical femoral fractures or osteonecrosis of jaw have been
      reported. Although incidence of atypical fractures is very rare compared to the
      number of the patients under bisphosphonate treatment, these conditions are
      thought caused by severely suppressed bone turnover by the treatment. If the
      osteoporotic patients under long term bisphophonates treatment have not high
      fracture risk, drug holiday should be considered.

PMID- 21960244
TI  - Enhanced sample preparation for quantitation of microcystins by matrix-assisted
      laser desorption/ionisation-time of flight mass spectrometry.
AB  - INTRODUCTION: Microcystins (MCs) are a group of cyanotoxins which pose a serious
      health threat when present in aquatic systems. Quantitative analysis of MCs by
      matrix-assisted laser desorption/ionisation-time of flight (MALDI-TOF) mass
      spectrometry has potential for the processing of large numbers of samples quickly
      and economically. The existing method uses an expensive internal standard and
      protocols that are incompatible with automated sample preparation and data
      acquisition. OBJECTIVE: To produce a MALDI-TOF sample preparation technique for
      the quantitation of MCs that not only maintains reproducibility and sensitivity,
      but is also compatible with an automated work-flow. METHODOLOGY: Seven different
      MALDI-TOF sample preparations were assessed for signal reproducibility
      (coefficient of variation) and sensitivity (method detection limit) using a cost
      effective internal standard (angiotensin I). The best preparation was then
      assessed for its quantitative performance using three different MC congeners
      ([Dha7] MC-LR, MC-RR and MC-YR). RESULTS: The sensitivity of six of the
      preparations was acceptable, as was the reproducibility for two thin-layer
      preparations performed on a polished steel target. Both thin-layer preparations
      could be used with a MALDI-TOF mass spectrometer that automatically acquires
      data, and one could be used in an automated sample preparation work-flow. Further
      investigation using the thin-layer spot preparation demonstrated that linear
      quantification of three different MC congeners was possible. CONCLUSION: The
      study demonstrates that with different sample preparation methods and modern
      instrumentation, large numbers of samples can be analysed rapidly for MCs at low
      cost.

PMID- 21960245
TI  - Long-term transfusion independence in del(5q) MDS patients who discontinue
      lenalidomide.

PMID- 21960246
TI  - Targeting survivin and p53 in pediatric acute lymphoblastic leukemia.
AB  - Despite advances in treatment and outcomes for patients with pediatric acute
      lymphoblastic leukemia (ALL), there continue to be subsets of patients who are
      refractory to standard chemotherapy and hematopoietic stem cell transplant.
      Therefore, novel gene targets for therapy are needed to further advance treatment
      for this disease. RNA interference technology has identified survivin as a
      potential therapeutic target. Survivin, a member of the inhibitor of apoptosis
      (IAP) proteins and chromosome passenger complex, is expressed in hematologic
      malignancies and overexpressed in relapsed pediatric ALL. Our studies show that
      survivin is uniformly expressed at high levels in multiple pediatric ALL cell
      lines. Furthermore, silencing of survivin expression in pediatric ALL cell lines
      as well as primary leukemic blasts reduces viability of these cells. This
      includes cell lines derived from patients with relapsed disease featuring
      cytogenetic anomalies such as t(12;21), Philadelphia chromosome t(9;22), t(1;19)
      as well as a cell line carrying t(17;19) from a patient with de novo ALL.
      Furthermore, inhibition of survivin increases p53-dependent apoptosis that can be
      rescued by inhibition of p53. Finally, a screen of randomly selected primary
      patient samples confirms that survivin-specific small interfering RNA and
      survivin-targeted drug, YM155, effectively reduce viability of leukemic blasts.

PMID- 21960247
TI  - c-Myb and its target Bmi1 are required for p190BCR/ABL leukemogenesis in mouse
      and human cells.
AB  - Expression of c-Myb is required for normal hematopoiesis and for proliferation of
      myeloid leukemia blasts and a subset of T-cell leukemia, but its role in B-cell
      leukemogenesis is unknown. We tested the role of c-Myb in p190(BCR/ABL)-dependent
      B-cell leukemia in mice transplanted with p190(BCR/ABL)-transduced marrow cells
      with a c-Myb allele (Myb(f/d)) and in double transgenic p190(BCR/ABL)/Myb(w/d)
      mice. In both models, loss of a c-Myb allele caused a less aggressive B-cell
      leukemia. In p190(BCR/ABL)-expressing human B-cell leukemia lines, knockdown of c
      Myb expression suppressed proliferation and colony formation. Compared with c
      Myb(w/f) cells, expression of Bmi1, a regulator of stem cell proliferation and
      maintenance, was decreased in pre-B cells from Myb(w/d) p190(BCR/ABL) transgenic
      mice. Ectopic expression of a mutant c-Myb or Bmi1 enhanced the proliferation and
      colony formation of Myb(w/d) p190(BCR/ABL) B-cells; by contrast, Bmi1
      downregulation inhibited colony formation of p190(BCR/ABL)-expressing murine B
      cells and human B-cell leukemia lines. Moreover, c-Myb interacted with a segment
      of the human Bmi1 promoter and enhanced its activity. In blasts from 19 Ph(1)
      adult acute lymphoblastic leukemia patients, levels of c-Myb and Bmi1 showed a
      positive correlation. Together, these findings support the existence of a c-Myb
      Bmi1 transcription-regulatory pathway required for p190(BCR/ABL) leukemogenesis.

PMID- 21960248
TI  - With age comes wisdom: decision making in younger and older adults.
AB  - In two experiments, younger and older adults performed decision-making tasks in
      which reward values available were either independent of or dependent on the
      previous sequence of choices made. The choice-independent task involved learning
      and exploiting the options that gave the highest rewards on each trial. In this
      task, the stability of the expected reward for each option was not influenced by
      the previous choices participants made. The choice-dependent task involved
      learning how each choice influenced future rewards for two options and making the
      best decisions based on that knowledge. Younger adults performed better when
      rewards were independent of choice, whereas older adults performed better when
      rewards were dependent on choice. These findings suggest a fundamental difference
      in the way in which younger adults and older adults approach decision-making
      situations. We discuss the results in the context of prominent decision-making
      theories and offer possible explanations based on neurobiological and behavioral
      changes associated with aging.

PMID- 21960249
TI  - The role of audiovisual processing in early conceptual development.

PMID- 21960250
TI  - Sociality, pathogen avoidance, and the neuropeptides oxytocin and arginine
      vasopressin.
AB  - Both humans and nonhumans have evolved a variety of mechanisms to recognize
      pathogen threat and a variety of adaptive behavioral responses to minimize
      exposure to it. Because social interactions facilitate the spread of infection
      among individuals, the ability to recognize and avoid infected and potentially
      infected individuals is crucial. The neuropeptides oxytocin (OT) and arginine
      vasopressin (AVP) are involved in mediating various facets of social behavior,
      including social recognition and responses to salient social threats. Results of
      studies with rodents have revealed that OT and AVP are also associated with the
      olfactory-mediated recognition and avoidance of actually or potentially infected
      individuals. The evidence reviewed here suggests that OT and AVP likely play
      parallel roles in modulating the recognition and avoidance of socially relevant
      pathogen threat in both humans and rodents.

PMID- 21960251
TI  - Emotion-regulation choice.
AB  - Despite centuries of speculation about how to manage negative emotions, little is
      actually known about which emotion-regulation strategies people choose to use
      when confronted with negative situations of varying intensity. On the basis of a
      new process conception of emotion regulation, we hypothesized that in low
      intensity negative situations, people would show a relative preference to choose
      to regulate emotions by engagement reappraisal, which allows emotional
      processing. However, we expected people in high-intensity negative situations to
      show a relative preference to choose to regulate emotions by disengagement
      distraction, which blocks emotional processing at an early stage before it
      gathers force. In three experiments, we created emotional contexts that varied in
      intensity, using either emotional pictures (Experiments 1 and 2) or unpredictable
      electric stimulation (Experiment 3). In response to these emotional contexts,
      participants chose between using either reappraisal or distraction as an emotion
      regulation strategy. Results in all experiments supported our hypothesis. This
      pattern in the choice of emotion-regulation strategies has important implications
      for the understanding of healthy adaptation.

PMID- 21960252
TI  - A neon-matrix isolation study of the reaction of non-energetic H-atoms with CO
      molecules at 3 K.
AB  - The efficiency of HCO formation stemming from non-energetic H-atoms and CO
      molecules is highlighted both in the condensed phase and within a neon matrix
      environment, which is half-way between the condensed-phase and gas-phase. Our
      experiments demonstrated that HCO production within the neon-matrix needed very
      little or no activation energy. The efficiency of HCO formation depended only on
      the capability of H-atoms to diffuse in the solid and to subsequently encounter
      CO molecules. The novelty of the presented matrix experiment sheds light on the
      debated question of whether activation energy is required in order to produce
      HCO, because of the use of non-energetic ground state H-atoms within the neon
      matrix.

PMID- 21960253
TI  - Mass-spectrometric studies of new 6-nitroquipazines-serotonin transporter
      inhibitors.
AB  - Six synthesized 6-nitroquipazine derivatives were examined by electron ionization
      (EI) and electrospray ionization (ESI) mass spectrometry in positive and negative
      ion mode. The compounds exhibit high affinity for the serotonin transporter
      (SERT) and belong to a new class of SERT inhibitors. The EI mass spectra
      registered in negative ion mode showed prominent molecular ions for all the
      compounds studied. All EI mass spectra and all ESI mass spectra showed similar
      fragmentation pathways of molecular ions, but the pathways differed between EI
      and ESI. The differences were explained with the aid of theoretical evaluation of
      the stability of the respective radical ions (EI MS) and protonated ions (ESI
      MS).

PMID- 21960254
TI  - A novel particle sampling system for physico-chemical and toxicological
      characterization of emissions.
AB  - Several studies have shown that combustion-derived fine particles cause adverse
      health effects. Previous toxicological studies on combustion-derived fine
      particles have rarely involved multiple endpoints and a detailed characterization
      of chemical composition. In this study, we developed a novel particle sampling
      system for toxicological and chemical characterization (PSTC), consisting of the
      Dekati Gravimetric Impactor (DGI) and a porous tube diluter. Physico-chemical and
      toxicological properties of the particles emitted from various combustion sources
      were evaluated in two measurement campaigns. First, the DGI was compared with the
      High-Volume Cascade Impactor (HVCI) and to the Dekati Low-Pressure Impactor
      (DLPI), using the same dilution system and the same sampling conditions. Only
      small differences were observed in the mass size distributions, total particulate
      matter (PM), and particulate matter with diameter smaller than 1 um (PM(1))
      concentrations and geometric mass mean diameters (GMMD) between these three
      impactors. Second, the PSTC was compared with the HVCI sampling system, which has
      been optimal for collection of particulate samples for toxicological and chemical
      analyses. Differences were observed in the mass size distributions, total PM and
      PM(1) emissions, and GMMDs, probably due to the different sampling and dilution
      methods as well as different sampling substrates which affected the behavior of
      semi-volatile and volatile organic compounds. However, no significant differences
      were detected in the in vitro measurements of cytotoxicity between the samples
      collected with the PSTC and the HVCI systems. In measurements of genotoxicity,
      significant differences between the two sampling systems were seen only with the
      particles emitted from the sauna stove. In conclusion, due to compact size, PSTC
      is an applicable method for use in particle sampling as part of the toxicological
      and chemical characterization of particulate emissions from different combustion
      sources. It offers some advantages compared to the previously used high-volume
      sampling methods including compactness for field measurements, simple preparation
      of sample substrates and high extraction efficiency.

PMID- 21960255
TI  - A liquid drop RC filter apparatus for detection.
AB  - A new analytical detector based on a liquid drop resistor-capacitor (RC) filter
      is described, in which transformed gain vs. frequency curves are used to analyze
      compounds. This detector can be used to detect either charged or neutral species
      (that are dielectrically different) which are dissolved in a liquid (e.g., water,
      alcohol, solvent mixtures, etc.). This device was fabricated by modifying an
      electrowetting on dielectric (EWOD)-based experimental setup. When a liquid drop
      is placed on a dielectric surface, the system acts as a RC filter. At a given
      frequency, gain is a function of conductivity, surface tension, dielectric
      constant, double-layer thickness of the solid-liquid drop interface, as well as
      the applied voltage. Since different liquids and solutions have different
      physical properties, each liquid/solution has a unique curve (peak) in gain vs.
      frequency plot. This is the basic principle behind the detector. Different
      amounts of zinc chloride dissolved in water, benzalkonium chloride in water, 1
      methylimidazole in water, cetyltrimethyl-ammonium chloride (CTAC) in water, and
      CTAC dissolved in ethylene glycol solutions were tested with the detector as
      proof of principle. The device can be used as a stand-alone detector or can
      easily be coupled with droplet based microfluidic lab-on-a-chip systems such as
      EWOD-based microfluidic chips.

PMID- 21960256
TI  - Synthesis, characterization, and in vitro antitumor properties of gold(III)
      compounds with the traditional Chinese medicine (TCM) active ingredient
      liriodenine.
AB  - Liriodenine, an oxoaporphine alkaloid with anticancer activity isolated from
      Zanthoxylum nitidum (rutaceous anticancer traditional Chinese medicine), was
      selected as a bioactive ligand to react with HAuCl(4) and NaAuCl(4) to afford
      [LH][AuCl(4)] (1) and [AuCl(3)L] (2), respectively (where L is liriodenine). The
      structures of 1 and 2 were characterized by IR spectroscopy, electrospray
      ionization mass spectrometry, (1)H-NMR spectroscopy, and elemental analysis. The
      single-crystal X-ray diffraction analysis of 1 revealed that it is an ionic
      compound consisting of protonated liriodenine cation [LH](+) and [AuCl(4)](-)
      anion. The spectroscopic analysis showed that 2 is a coordination compound, in
      which one liriodenine coordinates to gold via its 7-N donor. In aqueous solution,
      1 is relatively stable, but 2 undergoes rapid hydrolysis. The in vitro
      cytotoxicity towards five human tumor cell lines shows that 1 and 2 manifest
      roughly similar biological behavior and appreciable antiproliferative properties,
      with IC(50) values falling in the 2-16 MUM range. The flow-cytometric analysis of
      1 and 2 suggests that both compounds induced an S-phase arrest. Compounds 1 and 2
      significantly poison topoisomerase I in vitro at low concentration (25 MUM or
      less). DNA binding studies indicate that both 1 and 2 interact with DNA mainly
      via intercalation between the neighboring base pairs of the DNA double helix.
      Electrostatic interactions of 1 and 2 with the polyanionic DNA phosphate backbone
      may reinforce the intercalation because both 1 and 2 are composed of planar
      cationic species.

PMID- 21960257
TI  - Type 1 copper site synthetic model complexes with increased redox potentials.
AB  - Reactions of NaSCPh(3) with (R(3)tacn)Cu(OTf)(2) (R is Me, iPr; tacn is 1,4,7
      triazacyclononane; OTf is CF(3)SO(3)(-)) yield blue complexes identified as
      ((R(3)tacn)CuSCPh(3))(OTf) on the basis of UV-vis, resonance Raman, and electron
      paramagnetic resonance (EPR) spectroscopy and electrospray ionization mass
      spectrometry. These complexes exhibit spectroscopic properties typical of type 1
      copper sites in proteins, including diagnostic Spi -> Cu(d(x(2)-y(2))) ligand-to
      metal charge transfer transitions at approximately 610-630 nm and small A(||)
      values in EPR spectra of less than 100 * 10(-4) cm(-1). Cyclic voltammetry
      experiments revealed redox potentials for the complexes similar to those of
      several low-potential type 1 copper proteins (e.g., azurin, stellacyanin) and
      approximately 0.5 V higher than those of previously reported model compounds.
      Thus, the new complexes mimic key aspects of both the structure and the function
      of type 1 copper sites.

PMID- 21960258
TI  - Abnormal ECG patterns in chronic post-war PTSD patients: a pilot study.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) is a psychiatric syndrome
      associated with high levels of sympathetic activation of the autonomic nervous
      system. Individuals diagnosed with PTSD have a high propensity for
      electrocardiogram (ECG) abnormalities, atrioventricular conductive defects, and
      cerebrovascular incidents. PURPOSE: The aim of this study was to investigate ECG
      abnormalities in post-war PTSD patients. METHOD: This pilot study compared
      patients diagnosed with chronic post-war PTSD (n = 30) to patients diagnosed with
      major depressive disorder (MDD; n = 24) and healthy controls (n = 20). Following
      the completion of the Structured Clinical Interview for the DSM (SCID),
      participants were assessed with a standard 12-lead ECG. RESULTS: ECG
      abnormalities were observed in 66.7% of PTSD patients and 70.8% of MDD patients.
      In contrast, only 28.6% of the healthy control group showed ECG abnormalities.
      Multivariate logistic regression was used to adjust for participants' sex,
      smoking rate, education level, disease duration, and marital status. The results
      indicated that PTSD and MDD patients were more likely to have ECG abnormalities
      than the normal population (odds ratio for PTSD = 12.7, 95% confidence interval
      1.9-83.9; and odds ratio for MDD = 14.9, 95% confidence interval 1.3-170.5).
      CONCLUSION: PTSD and MDD patients showed elevated rates of ECG abnormalities
      compared to healthy controls. These findings have important implications for the
      medical treatment of PTSD and MDD given that both of these patient groups appear
      to be at increased risk of cardiovascular disorder.

PMID- 21960259
TI  - A comparison between artificial and natural water oxidation.
AB  - Two artificial water oxidation catalysts, the blue dimer and the Llobet catalyst,
      have been studied using hybrid DFT methods. The results are compared to those for
      water oxidation in the natural photosystem II enzyme. Studies on the latter
      system have now reached a high level of understanding, at present much higher
      than the one for the artificial systems. A recent high resolution X-ray
      structural investigation of PSII has confirmed the main features of the structure
      of the oxygen evolving complex (OEC) suggested by previous DFT cluster studies.
      The O-O bond formation mechanism suggested is of direct coupling (DC) type
      between an oxygen radical and a bridging oxo ligand. A similar DC mechanism is
      found for the Llobet catalyst, while an acid-base (AB) mechanism is preferred for
      the blue dimer. All of them require at least one oxygen radical. Full energy
      diagrams, including both redox and chemical steps, have been constructed
      illustrating similarities and differences to the natural system. Unlike previous
      DFT studies, the results of the present study suggest that the blue dimer is rate
      limited by the initial redox steps, and the Llobet catalyst by O(2) release. The
      results could be useful for further improvement of the artificial systems.

PMID- 21960260
TI  - High-sensitivity C reactive protein as a biomarker for grading of childhood
      asthma in relation to clinical classification, induced sputum cellularity, and
      spirometry.
AB  - BACKGROUND: Asthma is the most common chronic inflammatory disease in childhood
      and some reports have demonstrated systemic inflammation. The relevance of high
      sensitivity assays for C-reactive protein (hs-CRP), which are known to be a
      sensitive marker of low-grade systemic inflammation, has not been fully studied
      in childhood asthma. AIM OF STUDY: This cross sectional case-control study aimed
      at evaluating serum hs-CRP in asthmatic children with different grades of
      severity and control. METHODS: Serum hs-CRP, sputum cytology study, and forced
      expiratory volume in 1 sec (FEV1) % of predicted for age and sex were estimated
      in 60 asthmatic children (30 uncontrolled steroid-naive, and 30 controlled on
      inhaled steroid). They were recruited from Pediatric Chest Clinic, Children's
      Hospital, Ain Shams University. Sixty healthy children-age and sex-matched were
      included as a control group. RESULTS: Serum hs-CRP concentrations were
      significantly higher in asthmatics than in controls with a median of 1.93 mg/L
      and 0.24 mg/L, respectively. Serum hs-CRP levels were significantly higher in
      uncontrolled steroid-naive asthmatics than those controlled on inhaled steroid
      with a median of 3.15 mg/L and 1.55 mg/L, respectively. Serum hs-CRP showed a
      sensitivity of 72% and a specificity of 93%. CONCLUSIONS: Despite that pulmonary
      function tests and clinical classification are the gold standard for grading of
      asthma, hs-CRP can be considered as a new marker for assessment of different
      grades of asthma severity and control. It can be used for indirect detection and
      monitoring of airway inflammation, disease severity, and response to steroid
      treatment in asthmatic children.

PMID- 21960261
TI  - Epigenetic regulation of miR-34b and miR-129 expression in gastric cancer.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs that play fundamental roles in
      diverse biological and pathological processes by targeting the expression of
      specific genes. Here, we identified 38 methylation-associated miRNAs, the
      expression of which could be epigenetically restored by cotreatment with 5-aza-2'
      deoxycytidine and trichostatin A. Among these 38 miRNAs, we further analyzed miR
      34b, miR-127-3p, miR-129-3p and miR-409 because CpG islands are predicted
      adjacent to them. The methylation-silenced expression of these miRNAs could be
      reactivated in gastric cancer cells by treatment with demethylating drugs in a
      time-dependent manner. Analysis of the methylation status of these miRNAs showed
      that the upstream CpG-rich regions of mir-34b and mir-129-2 are frequently
      methylated in gastric cancer tissues compared to adjacent normal tissues, and
      their methylation status correlated inversely with their expression patterns. The
      expression of miR-34b and miR-129-3p was downregulated by DNA hypermethylation in
      primary gastric cancers, and the low expression was associated with poor
      clinicopathological features. In summary, our study shows that tumor-specific
      methylation silences miR-34b and miR-129 in gastric cancer cells.

PMID- 21960263
TI  - Retractions.

PMID- 21960262
TI  - Vegetables and fruits consumption and risk of esophageal and gastric cancer
      subtypes in the Netherlands Cohort Study.
AB  - Prospective epidemiologic data on vegetables and fruits consumption and risk of
      subtypes of esophageal and gastric cancer are sparse. We studied the association
      between vegetables and fruits consumption and risk of esophageal squamous cell
      carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia adenocarcinoma
      (GCA) and gastric noncardia adenocarcinoma (GNCA) in the Netherlands Cohort
      Study. In 1986, 120,852 Dutch men and women aged 55-69 filled out a questionnaire
      on diet and other cancer risk factors. After 16.3 years of follow-up, 101 ESCC,
      144 EAC, 156 GCA, 460 GNCA cases and 4,035 subcohort members were available for
      case-cohort analysis using Cox proportional hazards models. Multivariable
      adjusted incidence rate ratios (RRs) were generally below unity. Total vegetable
      consumption was nonsignificantly inversely associated with EAC and ESCC risk, but
      not with GCA and GNCA risk. Significant inverse associations were observed for
      raw vegetables and EAC risk [RR per 25 g/day: 0.81, 95% confidence interval (CI)
      0.68-0.98], and Brassica vegetables and GCA risk (RR per 25 g/day: 0.72, 95% CI
      0.54-0.95). Total fruit consumption was associated with a nonsignificantly
      decreased EAC risk. Citrus fruits were inversely associated with EAC and GCA risk
      (RRs for highest vs. lowest intake: 0.55, 95% CI 0.31-0.98 and 0.38, 95% CI 0.21
      0.69, respectively). Specifically for current smokers, vegetables and possibly
      also fruits intake was inversely associated with ESCC and EAC risk. Consumption
      of (specific groups of) vegetables and fruits may protect against subtypes of
      esophageal and gastric cancer.

PMID- 21960271
TI  - Enhanced reducing equivalent generation for 1,3-propanediol production through
      cofermentation of glycerol and xylose by Klebsiella pneumoniae.
AB  - 1,3-Propanediol (1,3-PD) biosynthesis plays a key role in NADH consumption to
      regulate the intracellular reducing equivalent balance of Klebsiella pneumoniae.
      This study aimed to increase reducing equivalent for enhancing 1,3-PD production
      through cofermentation of glycerol and xylose. Adding xylose as cosubstrate
      resulted in more reducing equivalent generation and higher cell growth. In batch
      fermentation under microaerobic condition, the 1,3-PD concentration, conversion
      from glycerol, and biomass (OD(600)) relative to cofermentation were increased
      significantly by 9.1%, 20%, and 15.8%, respectively. The reducing equivalent
      (NADH) was increased by 1-3 mg/g (cell dry weight) compared with that from
      glycerol alone. Furthermore, 2,3-butannediol was also doubly produced as major
      byproduct. In fed-batch fermentation with xylose as cosubstrate, the final 1,3-PD
      concentration, conversion from glycerol, and productivity were improved evidently
      from 60.78 to 67.21 g/l, 0.52 to 0.63 mol/mol, and 1.64 to 1.82 g/l/h,
      respectively.

PMID- 21960272
TI  - Thermodynamics of chitinase partitioning in soy lecithin liposomes and their
      storage stability.
AB  - The goal of this study was to define the partitioning behavior of chitinase from
      Trichoderma spp. in soy lecithin liposomes, using a thermodynamic approach based
      on the partitioning variation with temperature. An effort has been made to define
      the liposomes, as well as free and immobilized enzyme stability during storage at
      4 and 25  degrees C. The partition coefficients (K (o/w)) were greater than 1;
      therefore, the standard free energies of the enzyme transfer were negative,
      indicating an affinity of the enzymes for encapsulation in liposomes. The
      enthalpy calculation led to the conclusion that the process is exothermic. The
      presence of enzyme decreased the liposome storage stability from 70 days to an
      approximately 20 days at 25  degrees C and 30 days at 4  degrees C. Monitoring of
      the liposome's diameter demonstrated that their size and concentration decreased
      during storage. The liposome's diameters ranged from 1.06 to 3.30 MUm. The higher
      percentage of liposome corresponded to a diameter range from 1.06 to 1.34 MUm.
      This percentage increased during storage. There were no evidences for liposome
      fusion process. The stability of immobilized enzyme was increased in comparison
      with free chitinase.

PMID- 21960273
TI  - Endo-inulinase stabilization by pyridoxal phosphate modification: a kinetics,
      thermodynamics, and simulation approach.
AB  - The structural and storage and functional thermostabilization of endo-inulinase
      (EC 3.2.1.7) through semi-rational modification of surface accessible lysine
      residues by pyridoxal-5'-phosphate (PLP) and ascorbate reduction have been
      explored. Improved stability was observed on modifications in the absence or
      presence of inulin, which indicates storage or functional thermostabilization,
      respectively. Comparisons have been made between non-modified and modified enzyme
      by the determination of Tm as an indicator of structural stability, temperature
      dependent half-lives (t1/2), energy barrier of the inactivation process, and
      thermodynamic parameters (DeltaH, DeltaG, and DeltaS) in a storage
      thermostability approach. These parameters coincided well with the observed
      stabilization of the engineered enzyme. Moreover, relative activities with
      sucrose and inulin were determined for non-modified and modified endo-inulinases
      at different temperatures. A comparison of the sucrose-to-inulin ratios of the
      initial rate of hydrolysis as an indicator of substrate specificity revealed
      about twofold improvement in inulinase versus sucrose activity by enzyme
      modification. Molecular dynamics simulations and molecular docking approaches
      were employed to explain the observed structural and functional
      thermostabilization of endo-inulinase upon modification. We hypothesize the
      establishment of intramolecular interactions between the covalently attached PLP
      Lys381 and Arg526 and Ser376 residues as a representative of modification
      originated intramolecular contacts in the modified enzyme.

PMID- 21960274
TI  - Metabolic flux analysis and principal nodes identification for daptomycin
      production improvement by Streptomyces roseosporus.
AB  - In the present work, a comprehensive metabolic network of Streptomyces
      roseosporus LC-54-20 was proposed for daptomycin production. The analysis of
      extracellular metabolites throughout the batch fermentation was evaluated in
      addition to daptomycin and biomass production. Metabolic flux distributions were
      based on stoichiometrical reaction as well as the extracellular metabolites
      fluxes. Experimental and calculated values for both the specific growth rate and
      daptomycin production rate indicated that the in silico model proved a powerful
      tool to analyze the metabolic behaviors based on the analysis under different
      initial glucose concentrations throughout the fermentation. Through manipulating
      different pH values, the production rates of various extracellular metabolites
      were also presented in this paper. Flux distribution variations revealed that the
      daptomycin production could be significantly influenced by the branch points of
      glucose 6-phosphate, 3-phosphoglycerate, phosphoenolpyruvate, pyruvate, and
      oxaloacetate. The five principal metabolites were certified as the flexible nodes
      and could form potential bottlenecks for a further enhancement of daptomycin
      production. Furthermore, various concentrations of the five precursors were added
      into the batch fermentation and led to the enhancement of daptomycin
      concentration and production rate.

PMID- 21960275
TI  - Kinetic stability modelling of keratinolytic protease P45: influence of
      temperature and metal ions.
AB  - The activity and kinetic stability of a keratinolytic subtilisin-like protease
      from Bacillus sp. P45 was investigated in 100 mM Tris-HCl buffer (pH 8.0;
      control) and in buffer with addition of Ca(2+) or Mg(2+) (1-10 mM), at different
      temperatures. Addition of 3 mM Ca(2+) or 4 mM Mg(2+) resulted in a 26% increment
      on enzyme activity towards azocasein when compared to the control (100%; without
      added Ca(2+) or Mg(2+)) at 55  degrees C. Optimal temperature for activity in the
      control (55  degrees C) was similar with Mg(2+); however, temperature optimum was
      increased to 60  degrees C with 3 mM Ca(2+), displaying an enhancement of 42% in
      comparison to the control at 55  degrees C. Stability of protease P45 in control
      buffer and with Mg(2+) addition was assayed at 40-50  degrees C, and at 55-62 
      degrees C with Ca(2+) addition. Data were fitted to six kinetic inactivation
      models, and a first-order equation was accepted as the best model to describe the
      inactivation of protease P45 with and without metal ions. The kinetic and
      thermodynamic parameters obtained showed the crucial role of calcium ions for
      enzyme stability. As biocatalyst stability is fundamental for
      commercial/industrial purposes, the stabilising effect of calcium could be
      exploited aiming the application of protease P45 in protein hydrolysis.

PMID- 21960276
TI  - Expression and characterization of a novel propionyl-CoA dehydrogenase gene from
      Candida rugosa in Pichia pastoris.
AB  - The propionyl-CoA dehydrogenase (PACD) gene was firstly cloned from Candida
      rugosa by the cDNA RACE technique. The 6* His-tagged recombinant PACD gene was
      expressed in Pichia pastoris GS115 and purified with Ni-NTA affinity
      chromatography. SDS-PAGE analysis and Western blotting revealed that the
      molecular mass of the purified PACD was 49 kDa. The results showed that the
      recombinant protein had the activity of catalyzing propionyl-CoA to acrylyl-CoA.
      The K (m), k (cat), and V (max) values of the purified PACD were calculated to be
      40.86 MUM, 0.566 s(-1) and 0.693 U mg(-1) min(-1). The optimal temperature and pH
      of the purified PACD were 30  degrees C and 7.0, respectively. The recombinant
      PACD maintained 76.3%, 30.1%, and 4.3% of its original activity after 2 h
      incubation in standard buffer at 30, 40, and 50  degrees C, respectively. Mg(2+)
      had an activating effect on the enzyme, while Mn(2+), Ca(2+), Zn(2+), and Cu(2+)
      had weak inhibition. Since PACD catalyzed the key step (from propionyl-CoA to
      acrylyl-CoA) in the modified beta-oxidation pathway from glucose to 3
      hydroxypropionic acid (3-HP), the integration of recombinant PACD could benefit
      the engineered strains for effective production of 3-HP from the most abundant
      biomass-sugars.

PMID- 21960278
TI  - Lack of association between proline dehydrogenase (oxidase) 1 polymorphisms and
      schizophrenia in a Korean population.

PMID- 21960277
TI  - Prediction of biological functions of Shewanella-like protein phosphatases
      (Shelphs) across different domains of life.
AB  - PPP protein phosphatases are an important enzyme family involved in a variety of
      aspects of cellular signalling and metabolism. PPPs are ubiquitous in eukaryotes,
      and are also present in many bacteria. Canonical eukaryotic PPP phosphotases are
      represented by five major subfamilies (PP1, PP2A, calcineurin, PP5 and PPEF/PP7).
      We previously reported that three "bacterial-like" PPP groups span the prokaryote
      eukaryote boundary, including "Shewanella-like" phosphatases (Shelphs), which are
      in the focus of this study. Here we predict possible biological functions and
      functional partners of Shelphs by examining composition of bacterial operons and
      expression data for eukaryotes available in public databases. In Arabidopsis
      thaliana, the predicted possible roles include light-dependent regulation of
      chloroplast functions, signalling between the nucleus and the chloroplast, and
      defence responses. In Plasmodium falciparum, Shelphs are predicted to be
      associated with host cell invasion. One isoform has been located in the apical
      complex, essential for the interaction with the host cell. This makes P.
      falciparum Shelphs obvious potential candidates for therapeutic targets. Shelphs
      are also present in bacteria that constitute a considerable proportion of
      symbiotic microflora in humans. The predicted involvement of bacterial Shelphs in
      sensing and import of nutrients and extrusion of toxins may be relevant to the
      links between physiology of humans and our symbionts. Thus, despite the absence
      of Shelphs in animals, including humans, they may have a direct relationship to
      human health. Some predicted biological processes and potential functional
      partners of Shelphs are common between different bacterial and/or eukaryotic
      lineages, suggesting evolutionary conservation of some Shelph regulatory modules.

PMID- 21960279
TI  - 8-(p-CF3-cinnamyl)-modified purine nucleosides as promising fluorescent probes.
AB  - Natural nucleotides are not useful as fluorescent probes because of their low
      quantum yields. Therefore, a common methodology for the detection of RNA and DNA
      is the application of extrinsic fluorescent dyes coupled to bases in
      oligonucleotides. To overcome the many limitations from which fluorescent
      nucleotide-dye conjugates suffer, we have developed novel purine nucleosides with
      intrinsic fluorescence to be incorporated into oligonucleotide probes. For this
      purpose we synthesized adenosine and guanosine fluorescent analogues 7-25,
      conjugated at the C8 position with aryl/heteroaryl moieties either directly, or
      via alkenyl/alkynyl linkers. Directly conjugated analogues 7-14, exhibited high
      quantum yields, phi >0.1, and short lambda(em) (<385 nm). Alkynyl conjugated
      analogues 22-25, exhibited low quantum yields, phi <0.075, and lambda(em)<385 nm.
      The alkenyl conjugated analogues 15-21, exhibited lambda(em) 408-459 nm. While
      analogues 15,16, and 20 bearing an EDG on the aryl moiety, exhibited phi <0.02,
      analogues 17, and 21 with EWG on the aryl moiety, exhibited extremely high
      quantum yields, phi ~ 0.8, suggesting better intramolecular charge transfer. We
      determined the conformation of selected adenosine analogues. Directly conjugated
      analogue 8 and alkynyl conjugated analogue 22, adapted the syn conformation,
      whereas alkenyl conjugated analogue 15 adapted the anti conformation. Based on
      the long emission wavelengths, high quantum yields, anti conformation and base
      paring compatibility, we suggest analogues 17 and 21 for further development as
      fluorescent probes for the sensitive detection of genetic material.

PMID- 21960280
TI  - Application of a chiral metal-organic framework in enantioselective separation.
AB  - A modular approach for the synthesis of highly ordered porous and chiral
      auxiliary (Evans auxiliary) decorated metal-organic frameworks is developed. Our
      synthesis strategy, which uses known porous structures as model materials for
      incorporation of chirality via linker modification, can provide access to a wide
      range of porous materials suitable for enantioselective separation and catalysis.
      Chiral analogues of UMCM-1 have been synthesized and investigated for the
      enantioseparation of chiral compounds in the liquid phase and first promising
      results are reported.

PMID- 21960281
TI  - Two modes of information processing in the electrosensory system of the
      paddlefish (Polyodon spathula).
AB  - Paddlefish are uniquely adapted for the detection of their prey, small water
      fleas, by primarily using their passive electrosensory system. In a recent
      anatomical study, we found two populations of secondary neurons in the
      electrosensory hind brain area (dorsal octavolateral nucleus, DON). Cells in the
      anterior DON project to the contralateral tectum, whereas cells in the posterior
      DON project bilaterally to the torus semicircularis and lateral mesencephalic
      nucleus. In this study, we investigated the properties of both populations and
      found that they form two physiologically different populations. Cells in the
      posterior DON are about one order of magnitude more sensitive and respond better
      to stimuli with lower frequency content than anterior cells. The posterior cells
      are, therefore, better suited to detect distant prey represented by low-amplitude
      signals at the receptors, along with a lower frequency spectrum, whereas cells in
      the anterior DON may only be able to sense nearby prey. This suggests the
      existence of two distinct channels for electrosensory information processing: one
      for proximal signals via the anterior DON and one for distant stimuli via the
      posterior DON with the sensory input fed into the appropriate ascending channels
      based on the relative sensitivity of both cell populations.

PMID- 21960282
TI  - Visual discrimination of objects differing in spatial depth by goldfish.
AB  - Training experiments were performed to investigate the ability of goldfish to
      discriminate objects differing in spatial depth. Tests on size constancy should
      give insight into the mechanisms of distance estimation. Goldfish were
      successfully trained to discriminate between two black disk stimuli of equal size
      but different distance from the tank wall. Each stimulus was presented in a white
      tube so that the fish could see only one stimulus at a time. For each of eight
      training stimulus distances, the just noticeable difference in distance was
      determined at a threshold criterion of 70% choice frequency. The ratio of the
      retinal image sizes between training stimulus and comparison stimulus at
      threshold was about constant. However, in contrast to Douglas et al. (Behav Brain
      Res 30:37-42, 1988), goldfish did not show size constancy in tests with stimuli
      of the same visual angle. This indicates that they did not estimate distance, but
      simply compared the retinal images under our experimental conditions. We did not
      find any indication for the use of accommodation as a depth cue. A patterned
      background at the rear end of the tubes did not have any effect, which, however,
      does not exclude the possibility that motion parallax is used as a depth cue
      under natural conditions.

PMID- 21960283
TI  - Expression of toll-like receptors 2 and 3 on esophageal epithelial cell lines and
      on eosinophils during esophagitis.
AB  - BACKGROUND: The chronic disease eosinophilic esophagitis may be mediated by the
      innate immune system. Activation of toll-like receptors (TLRs) in other tissues
      is known to initiate eosinophil infiltration, thus TLRs may be a potential
      mediator of esophageal eosinophilia. Little is known about TLRs in the esophagus.
      AIMS: The purpose of this study was to identify the presence and activation of
      TLR2 and TLR3 on esophageal epithelial cell lines, primary epithelial cells and
      mucosal esophageal biopsies. METHODS: TLR2 and TLR3 were identified by
      immunocytochemistry and immunoblot. PCR assessed alterations to gene expression
      by activation of TLR2 and TLR3. Immunohistochemistry co-localized eosinophils and
      TLR2/TLR3 on esophageal biopsies. RESULTS: TLR2 and TLR3 were expressed on the
      esophageal adenocarcinoma cell lines TE-1 and TE-7, but only TLR3 was present on
      the esophageal epithelial cell line HET-1A. Thymic stromal lymphopoietin gene
      expression was altered in response to ligands zymosan and polyI:C, demonstrating
      activation. Primary esophageal epithelial cells did not express TLR2 or TLR3. In
      esophageal biopsies, TLR2 and TLR3 expression was limited to eosinophils and
      other immune cells during esophagitis. CONCLUSIONS: TLR2 and TLR3 expression on
      cultured esophageal epithelial cells differs from TLR2 and TLR3 expression in
      esophageal biopsies, which is limited to immune cells during esophagitis.

PMID- 21960284
TI  - Head or tail: the orientation of the small bowel capsule endoscope movement in
      the small bowel.
AB  - BACKGROUND AND AIMS: The diagnostic accuracy of capsule endoscopy has been
      suggested to be influenced by the direction of the passage in the intestine. It
      is currently unknown if a head-first or a tail-first orientation are equally
      common during the descent through the small bowel. The aim of the study was to
      identify the orientation of the capsule along the migration through the small
      bowel. METHODS: Thirty capsule endoscopies were reviewed by an experienced
      observer. The direction of the passage through the pylorus and the ileoceccal
      valve was recorded for all the examinations. In addition, detailed review of the
      passage of the capsule in different segments of the small bowel was undertaken
      for all the capsules. RESULTS: The capsule was significantly more likely to pass
      the pylorus head-first compared to tail-first (25 and 5 out of 30, respectively,
      OR 5, 95% CI 65-94%, P < 0.001). In 28/30 studies, the capsule exited the
      ileoceccal valve head-first (OR-14, 95% CI 77-99%, P < 0.001). In an immersion
      experiment, uneven distribution of weight of the capsule body was demonstrated
      with the head part (camera tip) being lighter than the tail part. CONCLUSIONS:
      The capsule endoscope usually passes through the pylorus and subsequent segments
      of the small bowel head-first. This observation suggests that the intestinal
      peristaltic physiology drives symmetrical bodies with their light part first. The
      principle of intestinal orientation by weight distribution may bear implications
      for capsules' design in the future.

PMID- 21960285
TI  - Endoscopic management of duodenal adenomas in familial adenomatous polyposis--a
      single-center experience.
AB  - BACKGROUND: Duodenal lesions (DLS) are common in patients with familial
      adenomatosis polyposis (FAP), and screening for duodenal adenocarcinoma (DA) is
      currently recommended. Endoscopic treatment of DLS is controversial. AIM: To
      report management and outcomes of endoscopic therapy for DLS in patients with
      FAP. METHODS: The records of patients with FAP who underwent endoscopic
      surveillance or therapy for DLS over a 15-year period were reviewed. Endoscopic
      intervention included endoscopic surveillance with biopsies, argon plasma
      coagulation (APC), endoscopic mucosal resection (EMR), EMR with APC, and
      ampullectomy. Main outcome measurements were recurrence and histology of DLS
      after endoscopic therapy, complications of endoscopic therapy, and need for
      duodenectomy. RESULTS: Seventy-one patients with FAP and DLS were identified from
      our endoscopy database as undergoing upper endoscopy for screening and/or
      surveillance (1995-2009). Mean follow up was 4.5 years (1-15 years). Seventy of
      the seventy-one (98.5%) patients had multiple flat DLS. Most of the patients were
      followed with yearly biopsies. APC was performed in 17 patients and EMR was
      performed in eight patients; in five of the eight EMR patients, APC was also
      performed to treat the edges of EMR site. During the follow up, 17/55 (31%)
      patients had histological progression (HP). HP was seen in 5/16 (31%) patients
      who underwent APC (one was lost to follow-up) and 12/40 (30%) patients followed
      with biopsies alone. Recurrence of lesions was noted in all patients. Two
      patients underwent duodenectomy. None of the patients developed DA during follow
      up. CONCLUSIONS: Endoscopic surveillance with directed endotherapy for DLS in FAP
      is feasible and safe when diligently performed.

PMID- 21960287
TI  - Intrahepatic knotting of a guide wire during endoscopic retrograde
      cholangiopancreatography.

PMID- 21960286
TI  - Down-regulation of CXCL12 by DNA hypermethylation and its involvement in gastric
      cancer metastatic progression.
AB  - BACKGROUND: Chemokine receptors are now known to play an important role in cancer
      growth and metastasis. However, there is little information regarding chemokine
      expression in gastric cancer. In this study, we examined CXCL12 expression in
      gastric cancer and also evaluated whether the down-regulation of CXCL12 is due to
      aberrant methylation of the gene. METHODS: CXCL12 expression was examined using
      real-time reverse-transcription polymerase chain reaction (RT-PCR),
      immunofluorescence, flow cytometry, and immunohistochemistry, and the methylation
      status of the gene was evaluated by methylation-specific PCR (MSP) in normal
      gastric and gastric cancer cell lines and 35 primary gastric carcinomas and
      corresponding nonmalignant gastric tissues. RESULTS: The down-regulation of
      CXCL12 was observed in gastric cancer cell lines and primary gastric carcinomas,
      while decreased expression of CXCL12 protein was significantly associated with
      lymph node metastasis and histological grade. And this down-regulation was found
      to be in accordance with aberrant methylation of the gene. Hypermethylation of
      the gene was observed in 65.7% (23 of 35) of the primary gastric carcinomas,
      while it was found in only 11.4% (4/35) of the corresponding nonmalignant
      tissues. Furthermore, CXCL12 expression was restored in gastric cancer cell lines
      after treatment with the demethylating agent, 5-aza-2'-deoxycytidine (5-Aza-dC),
      and demethylation of the highly metastatic cells SGC-7901 induced invasion
      suppression of the cells. For two CXCL12 receptors, CXCR4 and CXCR7, the mRNA
      levels remained almost unchanged with the 5-Aza-dC treatment. CONCLUSIONS:
      Collectively, our results suggest that the aberrant methylation of CXCL12
      frequently occurs in the down-regulation of CXCL12 in gastric cancers and that it
      may play a role in the metastasis of gastric cancer.

PMID- 21960288
TI  - Development of a rapid resolution liquid chromatographic method combined with
      chemometrics for quality control of Angelicae dahuricae radix.
AB  - INTRODUCTION: Angelicae dahuricae radix (Baizhi) is a widely used traditional
      Chinese medicine, for which the traditional processing method has been sun-drying
      after harvesting. In recent years this method has been replaced by sulphur
      fumigation for the sake of improving its appearance and pest control. Correct
      identification of sulphur-fumigated Baizhi and rapid finding of appropriate
      chemical markers for the quality control of Baizhi are of very great importance.
      OBJECTIVE: To develop a rapid and efficient method of rapid resolution liquid
      chromatography (RRLC) combined with chemometrics for discriminating sulphur
      fumigated Baizhi and controlling its quality. METHODOLOGY: The samples were
      separated on a Zorbax SB-C18-column with a gradient elution programme using
      methanol and water. The optimal RRLC method was validated in terms of linearity,
      precision, stability and recovery test. In addition, hierarchical clustering
      analysis (HCA) and principle component analysis (PCA) were applied to
      differentiate the different samples. RESULTS: All the constituents were well
      separated within 18 min. The results of chemical fingerprinting and quantitative
      analysis showed that the sulphur-fumigated method obviously destroyed the
      phytochemical profiles of Baizhi. Moreover, the sun-dried and sulphur-fumigated
      Baizhi could be clearly separated by HCA and PCA, and the critical markers such
      as oxypeucedanin and imperatorin accountable for such differences were ultimately
      screened out. CONCLUSION: This study revealed that sulphur-fumigation is an
      inappropriate approach for processing crude drugs and should be prohibited, and
      that the proposed RRLC method combined with chemometrics demonstrated an
      efficient strategy for quality control of Baizhi.

PMID- 21960289
TI  - Agreement of specific IgE and skin prick test in an unselected cohort of two-year
      old children.
AB  - The objective of this study was to evaluate the agreement between specific IgE
      (sIgE) and skin prick test (SPT), and the possible association between total IgE
      concentration and allergy-related disorders, when performed in an unselected
      cohort of 353 two-year olds. Median total IgE was within the reference value for
      two-year-old children regardless of the presence or absence of allergy-related
      disorders. 18.7% of the children had one or more positive reactions to SPT and/or
      sIgE in a panel of 12 allergens. Agreement between SPT and sIgE was variable,
      being best for peanut and poorest for milk. CONCLUSION: In young children total
      IgE is of limited value when evaluating allergy-related disorder. The lack of
      agreement among the positive tests of the sIgE and SPT for some allergens imply
      that these tests should not be used interchangeably, and both tests should
      probably be used complementarily when diagnosing atopic sensitization in small
      children.

PMID- 21960290
TI  - Health-related quality of life of pediatric patients with moderate to severe
      plaque psoriasis: comparisons to four common chronic diseases.
AB  - Health-related quality of life (HRQOL) is an important indicator of the burden of
      illness in moderate-to-severe plaque psoriasis. This study evaluated self
      reported generic HRQOL among pediatric patients with moderate-to-severe plaque
      psoriasis based on pooled baseline clinical trial data and compared them to four
      common chronic diseases and to a healthy sample. The Pediatric Quality of Life
      Inventory Version 4.0 (PedsQLTM 4.0) Generic Core Scales was administered to 208
      patients ages 4 to 17 years with stable, moderate-to-severe plaque psoriasis.
      Patients with moderate-to-severe plaque psoriasis were compared using one-sample
      t-tests to published PedsQLTM ( http://www.pedsql.org ) data on healthy children
      and pediatric patients with arthritis, psychiatric disorders, asthma, and
      diabetes. Pediatric patients with moderate-to-severe plaque psoriasis
      demonstrated significantly impaired physical, emotional, social, and school
      functioning in comparison to healthy children. The PedsQLTM Emotional and School
      Functioning Scales demonstrated the largest mean difference between the two
      groups (12.1, 11.1 points, respectively). In general, patients with plaque
      psoriasis demonstrated significantly more impaired generic HRQOL compared to
      patients with diabetes, comparable HRQOL to arthritis and asthma, and better
      HRQOL than psychiatric patients. In conclusion, the findings indicate that
      pediatric patients with moderate-to-severe plaque psoriasis have significantly
      impaired generic HRQOL in comparison to healthy children, and HRQOL generally
      comparable to other serious chronic diseases. These results demonstrate the
      significant negative impact of plaque psoriasis on the daily lives of these
      children from the patients' perspective.

PMID- 21960291
TI  - Perceived body shape, standardized body-mass index, and weight-specific quality
      of life of African-American, Caucasian, and Mexican-American adolescents.
AB  - PURPOSE: To examine associations among perceived body shape, standardized body
      mass index (zBMI), and weight-specific quality of life in African-American,
      Caucasian, and Mexican-American adolescents, aged 11-18 years. METHODS: Self
      report questionnaires were administered to 454 adolescents between 11 and 18
      years of age, of whom 53% were females, 33% were Caucasians, 30% were African
      Americans, and 37% were Mexican-Americans. Thirty-four percent had a healthy
      zBMI, 20% were overweight, and 46% were obese. RESULTS: In examining the adjusted
      R-square and R-square changes among stepwise regression models, the model with
      depressive symptoms (adjusted R-square = 0.34), perceived body shape (adjusted R
      square = 0.49), and female sex (adjusted R-square = 0.53) appears to be the most
      parsimonious and explanatory model for these data. Race/ethnicity and age did not
      enter the equations, due to their significance levels being greater than the
      probability of removal (0.1). CONCLUSIONS: This study demonstrates the importance
      of including the perceptual measures of weight-specific quality of life and
      perceived body shape in studies of and interventions with overweight and obese
      adolescents. Including these perceptual measures may provide increased insight
      into the motivations and values of overweight and obese youth and thus be useful
      for designing more effective weight interventions.

PMID- 21960292
TI  - Tumor detection from enhanced magnetic resonance imaging using fuzzy curvelet.
AB  - Effective medical image analysis is possible by the use of technique known as
      segmentation. Segmentation is a very challenging task because there is not any
      standard segmentation method is available for any medical application. In this
      article, we have proposed an automatic brain MR image segmentation method. Fast
      discrete curvelet transform and spatial fuzzy C-mean algorithm is used for noise
      removal and segmentation of brain MR image. Fuzzy entropy has been used for
      calculating adaptive and optimal threshold to separate out the image segments.
      Our proposed system is exclusively based on the information contained by the
      image itself. No extra information and no human intervention are required in our
      proposed system. We have tested our proposed system on different T1, T2 and PD
      brain MR images.

PMID- 21960293
TI  - Kyphoplasty in patients with multiple myeloma a retrospective comparative pilot
      study.
AB  - BACKGROUND: This retrospective study of 73 myeloma patients with painful
      vertebral lesions compares clinical and radiomorphological outcomes up to 2 years
      after additional kyphoplasty, radiation therapy or systemic treatment only.
      METHODS: We assessed pain, disability and radiomorphological parameters by visual
      analogue scale (VAS 0-100), Oswestry Disability Index and by re-evaluating
      available follow-up X-rays, respectively, in patients that were treated according
      to a clinical pathway. RESULTS: After 2 years the VAS score was reduced in all
      groups by 66 +/- 8.2 (kyphoplasty), 35 +/- 10.5 (radiation therapy) and 38 +/-
      20.5 (systemic therapy only). Only after kyphoplasty we observed a significantly
      reduced Oswestry Disability Index after 1 year (P < 0.001). Vertebral height
      remained stable after kyphoplasty (P = 0.283), in contrast to a progressive
      height loss in the other groups (P = 0.013 and P = 0.015 for radiation and
      systemic therapy only, respectively). Two years after kyphoplasty and
      radiotherapy the overall vertebral fracture incidence was significantly decreased
      as compared to the group after systemic therapy only (9.7% of all thoracic and
      lumbar vertebrae had new vertebral fractures after systemic therapy only, 2%
      after kyphoplasty (P < 0.001), 4.8% after radiation (P = 0.032)). CONCLUSION:
      Additional kyphoplasty was more effective than additional radiation or systemic
      therapy in terms of pain relief, reduction of pain associated disability and
      reduction of fracture incidence of the entire lumbar and thoracic spine.

PMID- 21960294
TI  - Assessment of emergency liver transplantation criteria in acute liver failure due
      to Amanita phalloides.
AB  - BACKGROUND AND AIMS: The emergency liver transplantation criteria for acute liver
      failure (ALF) due to Amanita phalloides (A. phalloides) intoxication are not
      consensual. The aims of this study were to evaluate the clinical outcomes, and to
      assess the accuracy of the current and specific criteria for emergency liver
      transplantation in predicting fatal outcome in ALF induced by A. phalloides.
      METHODS: Ten patients admitted with ALF induced by A. phalloides in a
      Gastroenterology Intensive Care Unit were studied. Indications for liver
      transplant were based on Clichy and/or King's College criteria. Specific criteria
      of Ganzert and Escudie were tested retrospectively. RESULTS: A. phalloides
      intoxication represented 11.6% of all admissions for ALF. Patients were admitted
      at a mean time of 60 +/- 20.4 h after ingestion. Eight patients met the Clichy
      and/or King's College criteria for emergency liver transplantation, seven of
      these patients were listed for transplant and only six patients were
      transplanted. Four (40%) patients died in a mean time of 4.8 +/- 0.74 days after
      ingestion. When applied retrospectively, Escudie's criteria showed 100% of
      accuracy for predicting fatal outcome, whereas, King's College, Clichy's and
      Ganzert's criteria had an accuracy of 90, 80 and 70%, respectively. A prothrombin
      index of less than 10% at day 3 after ingestion showed a positive predictive
      value of 100% and a negative predictive value of 60%. CONCLUSION: Escudie's
      criteria show the best accuracy for emergency liver transplant in ALF induced by
      A. phalloides. The assessment of these criteria at day 3 after ingestion shows a
      maximum positive predictive value, although with a decline in its negative
      predictive value.

PMID- 21960295
TI  - Accounting for non-optimal interactions in molecular recognition: a study of ion
      pi complexes using a QM/MM model with a dipole-polarisable MM region.
AB  - For a quantitative understanding of molecular structure, interaction and
      dynamics, accurate modelling of the energetics of both near-equilibrium and less
      optimal contacts is important. In this work, we explore the potential energy
      surfaces of representative ion-pi complexes. We examine the performance of a semi
      empirical QM/MM approach and the corresponding QM/MMpol model, where inducible
      point dipoles are additionally employed in the MM region. The predicted potential
      energy surfaces of cation-benzene complexes are improved by inclusion of explicit
      MM polarisation of the pi-molecule. For cation-formamide complexes, inducible
      dipoles appreciably improve energetic estimates at geometries forming non-optimal
      interactions. Energetic component analysis suggests that the implicit MM
      polarisation of the fixed charge QM/MM model mirrors the behaviour of the
      QM/MMpol dipole model for the energetics of near-equilibrium conformations.
      However, for complexes at less optimal orientations, the QM/MM model exhibits
      higher errors than the QM/MMpol approach, being unable to capture orientation
      dependent variations in polarisation energy.

PMID- 21960296
TI  - A stable cation of a CSi3P five-membered ring with a weakly coordinating chloride
      anion.
AB  - Don't count on counterions: The cyclic five-membered CSi(3)P cation 1 is
      synthesized in the reaction of benzamidinato-stabilized chlorosilylene and methyl
      phosphaalkyne. The presence of four pi electrons in 1 means it can be considered
      as a formal, heavier analogue of the cyclopentadienyl cation. Surprisingly the
      small counteranion (Cl(-)) does not contribute to the ring stability.

PMID- 21960297
TI  - [Vestibular implants might restore sense of balance].

PMID- 21960298
TI  - Gene expression during activation of Paracoccidioides brasiliensis conidia.
AB  - This study focuses on gene expression during crucial biological phenomena of the
      dimorphic fungal human pathogen Paracoccidioides brasiliensis, the conidia-to
      yeast (C-Y) transition and the conidia-to-mycelia (C-M) germination. We studied
      10 genes involved in different cellular functions: oxidative stress response
      (alternative oxidase (AOX), superoxide dismutase (SOD), flavodoxin, conserved
      hypothetical protein (Y20)); cell metabolism (glyceraldehyde-3-phosphate
      dehydrogenase (GADPH), cholestenol Delta-isomerase (ChDI), glycine dehydrogenase
      (GDh)) and heat shock response (Heat shock protein 90 (HSP90)), and cell
      synthesis and wall structure (glucan synthase-1 (GS-1), alpha-1,3-glucan synthase
      (alphaGS), and mannosyltransferase (MT)). Gene expression was measured during the
      first 72 h and 96 h of C-Y and C-M, respectively, previously shown to be a
      fundamental time frame for the consolidation of these cellular processes. The
      gene expression of AOX, GAPDH, HSP90, MT, alphaGS, and GDh was significantly
      increased during the C-Y transition, while SOD, ChDI, GAPDH, MT, GDh, and GS-1
      were increased during C-M germination. Additionally, some were highly expressed
      in each process: AOX, HSP90, and alphaGS during C-Y; SOD, ChDI, and GS-1 during C
      M. Altogether, these data add new information regarding gene expression during
      the C-Y and C-M processes. Future research will be targeted to further
      characterize the true relevance of the studied genes during the morphological
      transition, either during adaptation to the environment or to the infected host.

PMID- 21960300
TI  - Bleeding from major and minor duodenal papillae due to hemosuccus pancreaticus
      confirmed with side-view gastroduodenal endoscopy.

PMID- 21960299
TI  - Axonal transport of APP and the spatial regulation of APP cleavage and function
      in neuronal cells.
AB  - Over two decades have passed since the original discovery of amyloid precursor
      protein (APP). While physiological function(s) of APP still remain a matter of
      debate, consensus exists that the proteolytic processing of this protein
      represents a critical event in the life of neurons and that abnormalities in this
      process are instrumental in Alzheimer's disease (AD) pathogenesis. Specific
      molecular components involved in APP proteolysis have been identified, and their
      enzymatic activities characterized in great detail. As specific proteolytic
      fragments of APP are identified and novel physiological effects for these
      fragments are revealed, more obvious becomes our need to understand the spatial
      organization of APP proteolysis. Valuable insights on this process have been
      obtained through the study of non-neuronal cells. However, much less is known
      about the topology of APP processing in neuronal cells, which are characterized
      by their remarkably complex cellular architecture and extreme degree of
      polarization. In this review, we discuss published literature addressing various
      molecular mechanisms and components involved in the trafficking and subcellular
      distribution of APP and APP secretases in neurons. These include the relevant
      machinery involved in their sorting, the identity of membranous organelles in
      which APP is transported, and the molecular motor-based mechanisms involved in
      their translocation. We also review experimental evidence specifically addressing
      the processing of APP at the axonal compartment. Understanding neuron-specific
      mechanisms of APP processing would help illuminating the physiological roles of
      APP-derived proteolytic fragments and provide novel insights on AD pathogenesis.

PMID- 21960301
TI  - Dental functional status with and without tooth replacement in a Chinese adult
      population.
AB  - The objective of this study is to investigate the prevalence of missing teeth and
      prosthodontic replacements in a Chinese adult population using a hierarchical
      dental functional classification system. A total of 1,462 dentate subjects over
      40 years from Shandong Province, China were included and categorized in the
      functional classification system with and without tooth replacements. Depending
      on replacements, subjects could be reclassified (promoted) to categories
      reflecting higher functionality. "Promotions" were considered indicators for
      prosthodontic effectiveness. Homogeneities after dichotomization into functional
      categories appeared to be moderate to good. In the ">=10 teeth in each jaw"
      branch, mean number of teeth and posterior occluding pairs were 27.93 +/- 2.74
      and 7.10 +/- 1.94, respectively. In the branch "<10 teeth in each jaw," these
      figures were 16.17 +/- 5.54 and 1.49 +/- 1.45. Fixed dental prostheses (FDPs)
      added on average 3.5 artificial teeth; 46% of subjects with FDP promoted to a
      higher functional level. For removable dental prostheses (RDPs), these numbers
      were 8.5% and 79%, respectively. Promotion value per tooth added was
      significantly higher for FDPs. The classification system was able to quantify the
      effectiveness of teeth replacements. It was shown that RDPs were more effective
      when higher numbers of teeth were replaced, while FDPs were more effective per
      artificial tooth added.

PMID- 21960303
TI  - Alpha, beta and gamma motoneurons: functional diversity in the motor system's
      final pathway.
AB  - Since their discovery in the late 19th century our conception of motoneurons has
      steadily evolved. Motoneurons share the same general function: they drive the
      contraction of muscle fibers and are the final common pathway, i.e., the seat of
      convergence of all the central and peripheral pathways involved in motricity.
      However, motoneurons innervate different types of muscular targets. Ordinary
      muscle fibers are subdivided into three main subtypes according to their
      structural and mechanical properties. Intrafusal muscle fibers located within
      spindles can elicit either a dynamic, or a static, action on the spindle sensory
      endings. No less than seven categories of motoneurons have thereby been
      identified on the basis of their innervation pattern. This functional diversity
      has hinted at a similar diversity in the inputs each motoneuron receives, as well
      as in the electrical, or cellular, properties of the motoneurons that match the
      properties of their muscle targets. The notion of the diverse properties of
      motoneurons has been well established by the work of many prominent
      neuroscientists. But in today's scientific literature, it tends to fade and
      motoneurons are often thought of as a homogenous group, which develop from a
      given population of precursor cells, and which express a common set of molecules.
      We first present here the historical milestones that led to the recognition of
      the functional diversity of motoneurons. We then review how the intrinsic
      electrical properties of motoneurons are precisely tuned in each category of
      motoneurons in order to produce an output that is adapted to the contractile
      properties of their specific targets.

PMID- 21960302
TI  - Olfactory groove meningiomas: a retrospective study on 59 surgical cases.
AB  - We report here a retrospective study of 59 consecutive patients with olfactory
      groove meningiomas admitted and operated on between 1991 and 2008. Our goal was
      to characterize clinical features, treatment strategies, and outcome of these
      lesions. The surgical resection grade, the histological type and the presence of
      recurrences in the follow-up period were analyzed. Maximum tumor diameter
      determined by preoperative magnetic resonance imaging (MRI) examinations was
      between 2 and 11 cm. In 38 surgical procedures (64.4%), the tumor was removed
      through a bilateral subfrontal approach, in 12 (20.3%) a unilateral subfrontal
      approach was used, and in nine procedures (15.3%) a pterional approach was
      performed. The average age at presentation was 52 years (age: 20-76 years) and
      the sex ratio was 1.45:1 (females/males). According to Simpson's grading system,
      the degree of tumor removal was: grade I in 14 cases (23.8%), grade II in 38
      cases (64.4%), grade III in four cases (6.8%) and grade IV in three cases (5%).
      Fifty-six patients had benign meningiomas (94.9%) and three patients had atypical
      meningiomas (5.1%). Two patients (3.4%) died from pulmonary embolism and
      bronchopneumonia. There were recurrences in six patients (10.1%), between 9
      months and 12 years (mean 7.2 years) after surgery. The olfactory groove is a
      relatively frequent location for intracranial meningiomas, accounting for 9.1% of
      all intracranial meningiomas in our experience. Olfactory groove meningiomas tend
      to be clinically silent tumors until they are very large when symptoms or other
      abnormalities become evident. A surgical procedure adapted to the size and the
      extension of the tumor combined with microsurgical techniques allows total
      meningioma removal with good neurological outcome.

PMID- 21960304
TI  - Linear visuomotor transformations in midbrain superior colliculus control
      saccadic eye-movements.
AB  - It is well established that a localized population of neurons in the motor map of
      the midbrain superior colliculus (SC) drives a saccadic eye-head gaze shift.
      However, there is controversy as to how the brainstem saccade burst generators
      decode the SC activity. We focus on eye-movement generation by comparing two
      competing schemes from the recent literature that are both supported by
      neurophysiological evidence: the vector-averaging scheme versus the vector
      summation model. Whereas the former contains at least four nonlinearities to
      explain visuomotor planning and saccade execution, the latter relies
      predominantly on linear operations. We have demonstrated that the summation model
      accounts for the nonlinear main sequence of saccade kinematics, and predicted
      that this results from a spatial gradient in temporal burst profiles of SC cells:
      rostral cells have higher peak-firing rates and shorter burst durations than
      caudal cells. Yet, the number of spikes in their saccade-related bursts is
      identical. In contrast, the averaging model does not predict such activity
      profiles. We now also show that by incorporating the concept of predictive
      remapping in the spatial updating of saccade sequences, the phenomenon of target
      averaging in double-stimulation experiments, and the occurrence of goal-directed,
      but highly curved saccades in the double-step paradigm, can all be explained by
      the same linear summation mechanism. We argue that the linear model is more in
      line with neurophysiological data, while relying on fewer ad-hoc assumptions than
      the nonlinear vector-averaging scheme.

PMID- 21960305
TI  - The motor functions of the basal ganglia.
AB  - The past 25 years have seen a resurgence of interest in the basal ganglia. In the
      1980s, a series of studies yielded the now classic descriptions of basal ganglia
      connectivity and information flow that now dominates textbook descriptions. This
      was followed by the appearance of reward-based learning theories of
      corticostriatal function in which dopamine played a critical role in modulating
      corticostriatal connectivity. These advances have contributed enormously to our
      understanding of the basic principles of some of the circuits within these
      structures, and have dominated novel approaches to treatment of basal ganglia
      diseases. Yet even so, many of the common symptoms of Parkinson's disease or
      dystonia are incompletely understood, suggesting that these "dark basements of
      the brain" still harbor hidden secrets.

PMID- 21960306
TI  - Neural circuits of the cerebellum: hypothesis for function.
AB  - The rapid growth of cerebellar research is going to clarify several aspects of
      cellular and circuit physiology. However, the concepts about cerebellar
      mechanisms of function are still largely related to clinical observations and to
      models elaborated before the last discoveries appeared. In this paper, the major
      issues are revisited, suggesting that previous concepts can now be refined and
      modified. The cerebellum is fundamentally involved in timing and in controlling
      the ordered and precise execution of motor sequences. The fast reaction of the
      cerebellum to the inputs is sustained by specific cellular mechanisms ensuring
      precision on the millisecond scale. These include burst-burst reconversion in the
      granular layer and instantaneous frequency modulation on the 100-Hz band in
      Purkinje and deep cerebellar nuclei cells. Precisely timed signals can be used
      for perceptron operations in Purkinje cells and to establish appropriate
      correlations with climbing fiber signals inducing learning at parallel fiber
      synapses. In the granular layer, plasticity turns out to be instrumental to
      timing, providing a conceptual solution to the discrepancy between cerebellar
      learning and timing. The granular layer sub-circuit can be tuned by long-term
      synaptic plasticity and synaptic inhibition to delay the incoming signals over a
      100-ms range. For longer sequences, large circuit sections can be entrained into
      coherent activity in 100-ms cycles. These dynamic aspects, which have not been
      accounted for by original theories, could in fact represent the essence of
      cerebellar functioning. It is suggested that the cerebellum can, in this way,
      operate the realignment of temporally incongruent signals, allowing their binding
      and pattern recognition in Purkinje cells. The demonstration of these principles,
      their behavioral relevance and their relationship with internal model theories
      represent a challenge for future cerebellar research.

PMID- 21960308
TI  - Open questions in computational motor control.
AB  - Computational motor control covers all applications of quantitative tools for the
      study of the biological movement control system. This paper provides a review of
      this field in the form of a list of open questions. After an introduction in
      which we define computational motor control, we describe: a Turing-like test for
      motor intelligence; internal models, inverse model, forward model, feedback error
      learning and distal teacher; time representation, and adaptation to delay;
      intermittence control strategies; equilibrium hypotheses and threshold control;
      the spatiotemporal hierarchy of wide sense adaptation, i.e., feedback, learning,
      adaptation, and evolution; optimization based models for trajectory formation and
      optimal feedback control; motor memory, the past and the future; and conclude
      with the virtue of redundancy. Each section in this paper starts with a review of
      the relevant literature and a few more specific studies addressing the open
      question, and ends with speculations about the possible answer and its
      implications to motor neuroscience. This review is aimed at concisely covering
      the topic from the author's perspective with emphasis on learning mechanisms and
      the various structures and limitations of internal models.

PMID- 21960307
TI  - Functional recovery following motor cortex lesions in non-human primates:
      experimental implications for human stroke patients.
AB  - This review discusses selected classical works and contemporary research on
      recovery of contralesional fine hand motor function following lesions to motor
      areas of the cerebral cortex in non-human primates. Findings from both the
      classical literature and contemporary studies show that lesions of cortical motor
      areas induce paresis initially, but are followed by remarkable recovery of fine
      hand/digit motor function that depends on lesion size and post-lesion training.
      Indeed, in recent work where considerable quantification of fine digit function
      associated with grasping and manipulating small objects has been observed, very
      favorable recovery is possible with minimal forced use of the contralesional
      limb. Studies of the mechanisms underlying recovery have shown that following
      small lesions of the digit areas of primary motor cortex (M1), there is expansion
      of the digit motor representations into areas of M1 that did not produce digit
      movements prior to the lesion. However, after larger lesions involving the elbow,
      wrist and digit areas of M1, no such expansion of the motor representation was
      observed, suggesting that recovery was due to other cortical or subcortical areas
      taking over control of hand/digit movements. Recently, we showed that one
      possible mechanism of recovery after lesion to the arm areas of M1 and lateral
      premotor cortex is enhancement of corticospinal projections from the medially
      located supplementary motor area (M2) to spinal cord laminae containing neurons
      which have lost substantial input from the lateral motor areas and play a
      critical role in reaching and digit movements. Because human stroke and brain
      injury patients show variable, and usually poorer, recovery of hand motor
      function than that of nonhuman primates after motor cortex damage, we conclude
      with a discussion of implications of this work for further experimentation to
      improve recovery of hand function in human stroke patients.

PMID- 21960310
TI  - A Sandmeyer type reaction for bromination of 2-mercapto-1-methyl-imidazoline
      (N2C4H6S) into 2-bromo-1-methyl-imidazole (N2C4H5Br) in presence of copper(I)
      bromide.
AB  - 2-Mercapto-1-methyl-imidazoline (N(2)C(4)H(6)S) is converted at room temperature
      into 2-bromo-1-methyl-imidazole (N(2)C(4)H(5)Br) in presence of copper(I) bromide
      in acetonitrile-chloroform mixture via extrusion of sulfur as sulfate and
      oxidation of Cu(I) into Cu(II). 2-Bromo-1-methyl-imidazole was isolated as its
      self assembled tetranuclear Cu(II) cluster, [Cu(4)(eta(1)-N
      (N(2)C(4)H(5)Br)(4)(MU(4)-O)(MU-Br)(6)] 1 {eta(1)-N-(N(2)C(4)H(5)Br) = 2-bromo-1
      methyl-imidazole}.

PMID- 21960309
TI  - The challenge of the lantibiotics: synthetic approaches to thioether-bridged
      peptides.
AB  - The unique antibacterial properties and structural complexity of the lantibiotics
      has stimulated considerable interest in the development of methodology to
      synthesise these peptides. One of the most challenging issues has been the
      synthesis of polycyclic peptides with multiple thioether bridges between side
      chains, which are a characteristic feature of the lantibiotics. In this
      perspective, the different approaches to this problem, including solution-phase
      synthesis, solid-phase synthesis, biomimetic approaches and biotransformation
      strategies, are reviewed, highlighting the advances resulting from each of these
      approaches.

PMID- 21960311
TI  - The influence of KRAS and BRAF mutations on the efficacy of cetuximab-based first
      line therapy of metastatic colorectal cancer: an analysis of the AIO KRK-0104
      trial.
AB  - Our study investigated the impact of specific KRAS mutations and BRAF mutation on
      progression-free survival (PFS) and overall survival (OS) in patients with
      metastatic colorectal cancer (mCRC) treated within the AIO KRK-0104-trial as
      first-line therapy. In total, 146 (of 185) patients were included in this
      analysis. Seventy-nine patients presented with KRAS/BRAF wild-type (wt), 41
      patients with a KRAS codon 12 and nine patients with a KRAS codon 13 mutation.
      Seventeen patients presented a BRAF-mutated tumor. The patients of our study were
      treated with CAPIRI/CAPOX plus cetuximab. Major differences regarding PFS and OS
      were observed depending on the mutation of the tumor. PFS was 8 months in
      patients with wt-tumors, 5.8 months with codon 12-mutated, 9.9 months with codon
      13-mutated and 4.2 months with BRAF-mutated tumors. OS was 23.5 months in
      patients with wt-tumors, 18.9 months with codon 12-mutated, 26.2 months with
      codon 13-mutated and 13.0 months with BRAF-mutated tumors. Although the
      conventional separation of patients with KRAS wild-type versus KRAS mutant tumors
      did not have a significant impact on outcome parameters in the AIO KRK 0104
      trial, this analysis demonstrates that markedly differing results are obtained
      when subtypes of KRAS and BRAF mutation are taken into account.

PMID- 21960312
TI  - Long-term results of esophageal atresia: Helsinki experience and review of
      literature.
AB  - Esophageal atresia (EA) affects one in 2,840 newborns, and over half have
      associated anomalies that typically affect the midline. After EA repair in
      infancy, gastroesophageal reflux (GER) and esophageal dysmotility and respiratory
      problems are common. Significant esophageal morbidity associated with EA extends
      into adulthood. Surgical complications, increasing age, and impaired esophageal
      motility predict the development of epithelial metaplasia after repair of EA. To
      date, worldwide, six cases of esophageal cancer have been reported in young
      adults treated for EA. According to our data, the statistical risk for esophageal
      cancer is not higher than 500-fold that of the general population. However, the
      overall cancer incidence among adults with repaired EA does not differ from that
      of the general population. Adults with repaired EA have had significantly more
      respiratory symptoms and infections, as well as more asthma and allergies than
      does the general population. Nearly half the patients have bronchial
      hyperresponsiveness. Thoracotomy-induced rib fusion and gastroesophageal reflux
      associated columnar epithelial metaplasia are the most significant risk factors
      for the restrictive ventilatory defect that occurs in over half the patients.
      Over half the patients with repaired EA are likely to develop scoliosis. Risk for
      scoliosis is 13-fold after repair of EA in relation to that of the general
      population. Nearly half of the patients have had vertebral anomalies
      predominating in the cervical spine, and of these, most were vertebral fusions.
      The natural history of spinal deformities seems, however, rather benign, with
      spinal surgery rarely indicated.

PMID- 21960313
TI  - Thoracoscopic excision of the sympathetic chain: an easy and effective treatment
      for hyperhidrosis in children.
AB  - BACKGROUND: Thoracoscopic sympathectomy (TS) is an effective treatment for
      hyperhidrosis. Various surgical approaches are described in the literature. We
      describe the technique of thoracoscopic excision of the sympathetic chain done
      exclusively in children younger than 13 years. METHODS: All patients younger than
      13 years who underwent TS from 2006 at a single institution were prospectively
      identified and fully evaluated with emphasis on demographic data, age, surgical
      management, complications and follow-up. All patients were contacted again at the
      end of 2009 to complete a follow-up questionnaire. RESULTS: Twelve patients
      underwent TS between 2006 and 2009. Age ranged from 6 to 13 years. This involved
      T2-T3 excision for nine patients with isolated palmar hyperhidrosis, and T2-T3-T4
      excision for three with additional axillary hyperhidrosis. Six underwent
      bilateral TS at the same session and six underwent unilateral TS for the dominant
      side. Four of them had their contralateral operation performed 2-3 months later.
      Dry limbs were immediately achieved in all patients. Compensatory sweating (CS)
      was noted in eight patients. Complications included transient ptosis in two and
      mild recurrence in one. CONCLUSIONS: Thoracoscopic excision of the sympathetic
      chain is a simple and safe procedure that relieves hyperhidrosis in all cases and
      significantly improves the quality of life.

PMID- 21960314
TI  - A medical geology study of an arsenic-contaminated area in Kouhsorkh, NE Iran.
AB  - High concentrations of arsenic were determined in sediments from the Kouhsorkh
      area, Khorasan province, NE Iran. The main rock formations in the area consist of
      Tertiary volcanic rocks as Tuffaceous sandstone, polymictic conglomerate and
      andesite. Furthermore, some As-Sb-Au mineralization occurred in this area.
      Concentrations of arsenic in sediments were determined to range between 4.2 and
      268.2 ppm, exceeding US EPA (2004) limits. It seems that young volcanic activity
      is one of the most important factors for arsenic contamination in this area. The
      first stage of this medical geology study was done at 2 villages in the Kouhsorkh
      area in which the arsenic concentration in water is high. People in this
      residential area suffer from skin diseases including hyperpigmentation,
      hypopigmentation, keratosis on head, hands, and feet. The 24-h urine specimens
      were tested for arsenic, the level of total arsenic in urine were determined to
      range between 13.66 and 75.92 MUg/l day, exceeding permissible limits from 5 to
      40 MUg/day. More systematic studies are needed to determine the link between As
      exposure and its related diseases.

PMID- 21960315
TI  - Recent advances in the covalent modification of graphene with polymers.
AB  - Covalent binding of polymers to graphene represents an interesting alternative
      for the development of novel composite materials with a compendium of interfacial
      interactions. Through covalent linking, the concept of interface changes from a
      traditional view of interactions between components, such as van der Waals,
      hydrogen bonding, and so on, that is to say, at a polymer-filler interface, to a
      single compound concept where graphene forms an integral part of the polymeric
      chains. This feature article provides an overview of the strategies currently
      employed to functionalize graphene with polymers. We focus on the grafting-from
      and grafting-to methods used to bind polymers to graphene. The advantages and
      drawbacks, as well as the influence of each method on the final properties, are
      highlighted.

PMID- 21960317
TI  - A cross-national comparison of a shorter version of the person's relating to
      others questionnaire.
AB  - The shorter version of the Person's Relating to Others Questionnaire (PROQ3) is
      half the length of the earlier PROQ2. Both questionnaires were designed to
      measure negative relating as organized around a theoretical structure called the
      interpersonal octagon. Each questionnaire has an upper, lower, close and distant
      scale and four intermediate scales (e.g., upper close). As would be expected,
      moderately high positive correlations were observed between primary scales
      (upper, lower, close and distant) and neighbouring intermediate scales.
      Correlations diminished with increasing separation around the octagon. The
      psychometric properties of the PROQ3 were examined within four national samples.
      Alpha coefficients were consistently acceptable across samples. Gender
      differences varied between samples. Comparisons were made between the PROQ3 and a
      measure of the big five (International Personality Item Pool) and between the
      PROQ3 and two measures based upon the interpersonal circle (Revised Interpersonal
      Check List [ICL-R] and Circumplex Version of the Inventory of Interpersonal
      Problems [IIP-C]). It is important to note that, unlike with the PROQ3,
      significant negative correlations were observed between opposite scales of the
      ICL-R and opposite scales of the IIP-C. A confirmatory factor analysis provided
      support for most PROQ3 scales, although some overlap between scales was
      demonstrated. Correlations between the PROQ3 scales and the big five scales were
      either non-significant (two scales) or negative. Each PROQ3 scale correlated
      positively and meaningfully with a short sequence of scales of both the ICL-R and
      the IIP-C. Psychotherapy patients had higher mean scores than non-patients on
      four scales but non-patients had higher mean scores on two. Over the course of
      psychotherapy, the patients' mean score dropped significantly on six scales but
      rose significantly on one.

PMID- 21960318
TI  - First-line panitumumab plus irinotecan/5-fluorouracil/leucovorin treatment in
      patients with metastatic colorectal cancer.
AB  - PURPOSE: Panitumumab monotherapy is approved for KRAS wild-type (WT) metastatic
      colorectal cancer (mCRC) progressing after standard chemotherapy. This study
      evaluated first-line panitumumab plus FOLFIRI in patients with mCRC. METHODS: In
      this phase II, single-arm study, panitumumab (6 mg/kg) and FOLFIRI [irinotecan
      (180 mg/m(2)) and leucovorin (400 mg/m(2)) followed by a 5-fluorouracil 400
      mg/m(2) bolus and a 2,400-3,000 mg/m(2) continuous infusion] were administered
      every 14 days until progression. Data were analysed descriptively overall and by
      tumour KRAS status. RESULTS: KRAS data were available for 145/154 (94%) patients:
      59% KRAS WT and 41% mutant (MT); mean follow-up was 39.5 versus 35.8 weeks,
      respectively. Objective responses occurred in 49% of patients: 56% versus 38% in
      the KRAS WT versus MT groups [(18% difference (95% CI 1-35%); odds ratio 2.1 (95%
      CI 1.0-4.4)]; median duration of response was 13.0 versus 7.4 months. More
      patients in the WT group underwent R0 resection (8% vs. 5%); median progression
      free survival also favoured this group (8.9 vs. 7.2 months). The most common
      adverse events (any grade) were integument toxicities (98%), diarrhoea (79%) and
      stomatitis/oral mucositis (51%). CONCLUSIONS: As expected, consistently
      favourable efficacy was observed in patients with KRAS WT versus MT tumours
      receiving first-line panitumumab plus FOLFIRI treatment.

PMID- 21960320
TI  - Meeting report of the third Heidelberg myeloma workshop: current status and
      developments in diagnosis and therapy of multiple myeloma.

PMID- 21960319
TI  - Analysis of the contribution of nasopharyngeal epithelial cancer cells to the
      induction of a local inflammatory response.
AB  - PURPOSE: We investigated the local contribution of nasopharyngeal epithelial
      cancer cells to the inflammatory process. MATERIALS AND METHODS: THP-1 monocytes
      were treated with phorbol 12-myristate 13-acetate to induce the production of
      differentiated macrophages (D-THP-1), which were subsequently activated by
      lipopolysaccharide (LPS) (10 ng/ml). The production of pro-inflammatory cytokines
      in D-THP-1 cells was detected by ELISA and qRT-PCR. The effects of conditioned
      media harvested from LPS-treated D-THP-1 cells were investigated with regard to
      cell proliferation (MTT), production of pro-inflammatory cytokines (ELISA) and
      activation of NF-kappaB and STAT3 (western blot) in the nasopharyngeal epithelial
      cancer cell line 5-8F. RESULTS: LPS induced the production of the pro
      inflammatory cytokines TNF-alpha (875.1 +/- 68.31 pg/ml), IL-6 (42.2 +/- 5.32
      pg/ml), IL-1beta (9.6 +/- 1.34 pg/ml) and IL-8 (19.3 +/- 3.47 pg/ml) in D-THP-1
      cells significantly (P < 0.001) with similar results detected at the mRNA level.
      Exposure of 5-8F cells to conditioned medium from LPS-treated D-THP-1 cells
      significantly induced production of TNF-alpha (632.3 +/- 71.32 pg/ml), IL-6 (51.3
      +/- 3.57 pg/ml), IL-1beta (7.3 +/- 1.31 pg/ml) and IL-8 (20.1 +/- 2.36 pg/ml) (P
      < 0.01) and triggered significant activation of NF-kappaB and STAT3, which
      correlated with a concomitant degradation of IkappaBalpha and an increase in JAK2
      phosphorylation (P < 0.05). Moreover, the LPS-treated D-THP-1 conditioned media
      promoted the proliferation of 5-8F cells (P < 0.05). CONCLUSIONS: Nasopharyngeal
      epithelial cancer cells may play a significant role in maintaining and amplifying
      the inflammation process via activation of NF-kappaB and STAT3 pathway and
      through the local production of pro-inflammatory cytokines, which recruit and
      activate additional immune cells in the nasopharyngeal path and promote tumour
      progression.

PMID- 21960321
TI  - Stereotactic body radiation therapy in hepatocellular carcinoma and cirrhosis:
      evaluation of radiological and pathological response.
AB  - BACKGROUND: Loco-regional therapies for cirrhotic patients with hepatocellular
      carcinoma (HCC) who are awaiting liver transplantation (OLT) attempt to prevent
      tumor progression. However, there is limited data regarding the efficacy of
      stereotactic body radiation therapy (SBRT) as loco-regional treatment. METHODS:
      From 2006 to 2009, 27 HCC patients (AJCC I, II) listed for OLT underwent SBRT.
      Thirty-nine lesions were treated and 27 assessed radiologically. Seventeen
      patients had OLT, liver explants were analyzed and 22 lesions underwent
      pathological evaluation. RESULTS: In a cumulative analysis of all imaging, 30%
      had complete response, 7% had partial response, 56% were stable, and 7% had
      progression of disease. Of the 22 pathologically evaluated lesions, 37% were
      responders: 14% with complete response, 23% with partial response, and 63% with
      no response. Side effects from SBRT were recorded in three patients, which
      included nausea in two and liver decompensation in one. CONCLUSION: SBRT achieves
      total or partial radiological response in 37% of patients and total or partial
      pathological response in 37% of patients with early HCC in the setting of
      cirrhosis. SBRT may be a safe and effective alternative for local tumor control
      in patients with HCC and cirrhosis awaiting OLT.

PMID- 21960322
TI  - Supported colloidal nanoparticles in heterogeneous gas phase catalysis: on the
      way to tailored catalysts.
AB  - Using colloidally synthesized nanoparticles for the preparation of supported
      catalysts offers several advantages (e.g. precise control of particle size and
      morphology) when compared to traditional preparation techniques. Although such
      nanoparticles have already been very successfully used for catalytic applications
      in the liquid phase, applications in heterogeneous gas phase catalysis are still
      scarce. One aspect, usually considered as a problem, is organic stabilizers
      typically employed during the nanoparticle synthesis since they or their
      decomposition products are supposed to block catalytically active sites on the
      nanoparticle surface. Thus, in many studies so far, the removal of the organic
      ligands prior to use in gas phase catalysis has been proposed. In this
      perspective article, however, we will discuss a number of benefits such ligand
      shells may have for heterogeneous gas phase catalysis, including the protection
      against chemical modification, prevention of sintering and tuning of SMSI
      effects.

PMID- 21960323
TI  - Bridging for an isolated subtherapeutic INR: an evaluation of clinical practice
      patterns, outcomes, and costs from an anticoagulation clinic.
AB  - No formal recommendations support bridging patients taking warfarin for a
      subtherapeutic international normalized ratio (INR). This study aimed to: (1)
      characterize practices at one anticoagulation clinic, (2) evaluate adverse
      events, and (3) compare cost of bridging versus withholding bridging for
      subtherapeutic INR. A retrospective chart review of 320 patients having 546
      isolated subtherapeutic INR episodes included patients with an INR below their
      therapeutic range, preceded by two INRs within or above range. Bridged episodes
      required more frequent follow-up visits to achieve therapeutic INR (2.5 +/- 1.0
      vs. 2.2 +/- 0.6; P = 0.097), but fewer days until the INR returned to therapeutic
      range (6.8 +/- 5.0 vs. 18.9 +/- 16.0; P < 0.0001). The strongest predictor of
      bridging was the magnitude the INR fell below the therapeutic range, where those
      with a severely-low INR were 30-fold more likely to be bridged (P < 0.0001), and
      moderately-low INR episodes were 6-fold more likely to be bridged compared with
      mildly-low INR (P < 0.0001). Those at high thromboembolic risk were more likely
      to be bridged than at low-risk (OR 3.39 [1.50-7.68]; P = 0.0034). Increasing age
      reduced the likelihood of being bridged (OR 0.97 [0.95-0.99]; P = 0.0118).
      Adverse events were infrequent in both the bridged and non-bridged; thrombosis
      (2.0 vs. 0.7%), major bleeding (2.0 vs. 1.3%), minor bleeding (4.1 vs. 3.1%) and
      bruising (18.4 vs. 3.6%). Incremental cost difference of bridging was
      significantly greater for total cost ($967.13) and its components, direct medical
      ($951.32), transportation ($2.73) and productivity cost ($13.08). It is unclear
      if bridging for an isolated subtherapeutic INR reduces thrombosis risk, but it is
      associated with higher costs.

PMID- 21960324
TI  - [Clinical advances: research has to reach the patient].

PMID- 21960325
TI  - [Interventional treament of peripheral arterial disease and diabetic angiopathy].

PMID- 21960326
TI  - [Recent advances in adrenal diseases].

PMID- 21960327
TI  - [Immobility in the elderly: fitness to drive, gait and falls].

PMID- 21960328
TI  - [Chronic myeloid leukemia].

PMID- 21960329
TI  - [Vaccinations].

PMID- 21960330
TI  - [Intensive care in patients with asthma and COPD].

PMID- 21960331
TI  - [Diagnosis and treatment of mitral regurgitation].

PMID- 21960332
TI  - [Dialysis therapy and renal transplantation].

PMID- 21960333
TI  - [Thoracic oncology].

PMID- 21960334
TI  - [Spondyloarthritis including psoriatic arthritis].

PMID- 21960335
TI  - [Pancreatic diseases: update 2011].

PMID- 21960336
TI  - [Subcutaneous mass as initial manifestation of an osteolytic metastasis].
AB  - HISTORY AND CLINICAL FINDINGS: A 69-year-old woman was admitted for evaluation of
      a left occipital subcutaneous tumour which had grown during the preceding eight
      weeks from 2 * 2 cm to 4 * 4 cm. INVESTIGATIONS: Sonography revealed a pressure
      sensitive subcutaneous mass with osteolytic destruction in the occipital bone.
      Cranial magnetic resonance imaging confirmed the osteolytic lesion. Thoracic
      computed tomography showed a lesion in the upper left lobe of the lung with
      metastases in the hilar lymph nodes. DIAGNOSIS, TREATMENT AND COURSE:
      Transbronchial biopsy revealed a bronchial carcinoma. After resection of the
      osteolytic lesion its histology was confirmed to be an osseous metastasis of the
      carcinoma. Palliative chemotherapy and cranial irradiation were initiated.
      CONCLUSION: Solitary osteolytic lesions of the skull occur in the context of
      osseous metastases. Other possible causes include solitary plasmocytoma and
      eosinophilic granuloma.

PMID- 21960337
TI  - [Double ventricular repolarisation or ECG artefact?].

PMID- 21960338
TI  - [Prevention of stroke by blood pressure lowering].

PMID- 21960339
TI  - [Unclear cause of CK elevation].

PMID- 21960340
TI  - Child and adolescent psychiatry in Europe.

PMID- 21960341
TI  - Clinical outcomes of fertility-sparing treatments in young patients with
      epithelial ovarian carcinoma.
AB  - OBJECTIVE: To assess the clinical outcomes of fertility-sparing treatments in
      young patients with epithelial ovarian carcinoma (EOC). METHODS: A retrospective
      study of young EOC inpatients (<=40 years old) was performed during January 1994
      and December 2010 in eight institutions. RESULTS: Data were analyzed from 94
      patients treated with fertility-sparing surgery with a median follow-up time of
      58.7 months. As histologic grade increased, overall survival (OS) and disease
      free survival (DFS) of patients receiving fertility-sparing surgery declined.
      Neither staging surgery nor laparoscopy of early stage EOC with conservative
      surgery had a significant effect on OS or DFS. Normal menstruation recommenced
      after chemotherapy in 89% of the fertility-sparing group. Seventeen pregnancies
      among twelve patients were achieved by the end of the follow-ups. CONCLUSIONS:
      Fertility-sparing treatment for patients with EOC Stage I Grade 1 could be
      cautiously considered for young patients. The surgical procedure and surgical
      route might not significantly influence the prognosis. Standard chemotherapy is
      not likely to have an evident impact on ovarian function or fertility in young
      patients.

PMID- 21960342
TI  - Normal epigenetic inheritance in mice conceived by in vitro fertilization and
      embryo transfer.
AB  - An association between assisted reproductive technology (ART) and neurobehavioral
      imprinting disorders has been reported in many studies, and it seems that ART may
      interfere with imprint reprogramming. However, it has never been explored whether
      epigenetic errors or imprinting disease susceptibility induced by ART can be
      inherited transgenerationally. Hence, the aim of this study was to determine the
      effect of in vitro fertilization and embryo transfer (IVF-ET) on
      transgenerational inheritance in an inbred mouse model. Mice derived from IVF-ET
      were outcrossed to wild-type C57BL/6J to obtain their female and male line F2 and
      F3 generations. Their behavior, morphology, histology, and DNA methylation status
      at several important differentially methylated regions (DMRs) were analyzed by
      Morris water maze, hematoxylin and eosin (H&E) staining, and bisulfite genomic
      sequencing. No significant differences in spatial learning or phenotypic
      abnormality were found in adults derived from IVF (F1) and female and male line
      F2 and F3 generations. A borderline trend of hypomethylation was found in H19 DMR
      CpG island 3 in the female line-derived F3 generation (0.40+/-0.118, P=0.086).
      Methylation status in H19/Igf2 DMR island 1, Igf2 DMR, KvDMR, and Snrpn DMR
      displayed normal patterns. Methylation percentage did not differ significantly
      from that of adults conceived naturally, and the expression of the genes they
      regulated was not disturbed. Transgenerational integrity, such as behavior,
      morphology, histology, and DNA methylation status, was maintained in these
      generations, which indicates that exposure of female germ cells to hormonal
      stimulation and gamete manipulation might not affect the individuals and their
      descendents.

PMID- 21960343
TI  - Association of hypomethylation of LINE-1 repetitive element in blood leukocyte
      DNA with an increased risk of hepatocellular carcinoma.
AB  - Global DNA hypomethylation has been associated with increased risk for cancers of
      the colorectum, bladder, breast, head and neck, and testicular germ cells. The
      aim of this study was to examine whether global hypomethylation in blood
      leukocyte DNA is associated with the risk of hepatocellular carcinoma (HCC). A
      total of 315 HCC cases and 356 age-, sex- and HBsAg status-matched controls were
      included. Global methylation in blood leukocyte DNA was estimated by analyzing
      long interspersed element-1 (LINE-1) repeats using bisulfite-polymerase chain
      reaction (PCR) and pyrosequencing. We observed that the median methylation level
      in HCC cases (percentage of 5-methylcytosine (5mC)=77.7%) was significantly lower
      than that in controls (79.5% 5mC) (P=0.004, Wilcoxon rank-sum test). The odds
      ratios (ORs) of HCC for individuals in the third, second, and first (lowest)
      quartiles of LINE-1 methylation were 1.1 (95% confidence interval (CI) 0.7-1.8),
      1.4 (95% CI 0.8-2.2), and 2.6 (95% CI 1.7-4.1) (P for trend <0.001),
      respectively, compared to individuals in the fourth (highest) quartile. A 1.9
      fold (95% CI 1.4-2.6) increased risk of HCC was observed among individuals with
      LINE-1 methylation below the median compared to individuals with higher (>median)
      LINE-1 methylation. Our results demonstrate for the first time that individuals
      with global hypomethylation measured in LINE-1 repeats in blood leukocyte DNA
      have an increased risk for HCC. Our data provide the evidence that global
      hypomethylation detected in the easily obtainable DNA source of blood leukocytes
      may help identify individuals at risk of HCC.

PMID- 21960344
TI  - Genome-wide analysis of OCT4 binding sites in glioblastoma cancer cells.
AB  - OCT4, a member of the POU family of gene products, is an octamer motif-binding
      transcription factor. As it is known to play a crucial role in cancer processes
      including proliferation, invasion, and chemoradioresistance, it is important to
      identify the direct targets of OCT4 in living cancer cells. Here, chromatin
      immunoprecipitation-sequencing (ChIP-seq) was used to identify OCT4 binding sites
      in glioblastoma cancer cells. The results showed that 5438 OCT4 binding sites
      were localized in the glioblastoma cancer genome and that these sites contained a
      consensus sequence TTTkswTw (k=T or G, s=C or G, w=A or T), which occurred 3931
      times in 2312 OCT4 binding regions. Furthermore, binding motifs of some other
      transcription factors were identified in OCT4 binding regions. Our results
      provide a valuable dataset for understanding gene regulation mechanisms
      underlying the function of OCT4 in glioblastoma cancer.

PMID- 21960345
TI  - Comparative proteome analysis of Helicobacter pylori clinical strains by two
      dimensional gel electrophoresis.
AB  - OBJECTIVE: To investigate the pathogenic properties of Helicobacter pylori by
      comparing the proteome map of H. pylori clinical strains. METHODS: Two wild-type
      H. pylori strains, YN8 (isolated from biopsy tissue of a gastric cancer patient)
      and YN14 (isolated from biopsy tissue of a gastritis and duodenal ulcer patient),
      were used. Proteomic analysis, using a pH range of 3-10 and 5-8, was performed.
      The individual proteins were identified by quadrupole time-of-flight (Q-TOF) mass
      spectrometer and protein database search. RESULTS: Variation in spot patterns
      directed towards differential protein expression levels was observed between the
      strains. The gel revealed prominent proteins with several protein "families". The
      comparison of protein expressions of the two strains reveals a high variability.
      Differentially present or absent spots were observed. Nine differentially
      expressed protein spots identified by Q-TOF included adenosine triphosphate (ATP)
      binding protein, disulfide oxidoreductase B (DsbB)-like protein, N utilization
      substance A (NusA), ATP-dependent protease binding subunit/heat shock protein,
      hydantoin utilization protein A, seryl-tRNA synthetase, molybdenum ABC
      transporter ModD, and hypothetical proteins. CONCLUSIONS: This study suggests
      that H. pylori strains express/repress protein variation, not only in terms of
      the virulence proteins, but also in terms of physiological proteins, when they
      infect a human host. The difference of protein expression levels between H.
      pylori strains isolated from gastric cancer and gastritis may be the initiator of
      inflammation, and result in the different clinical presentation. In this
      preliminary study, we report seven differential proteins between strains, with
      molecule weights from approximately 10 kDa to approximately 40 kDa. Further
      studies are needed to investigate those proteins and their function associated
      with H. pylori colonization and adaptation to host environment stress.

PMID- 21960346
TI  - Imbalanced expression of mitogen-activated protein kinase phosphatase-1 and
      phosphorylated extracellular signal-regulated kinases in lung squamous cell
      carcinoma.
AB  - OBJECTIVE: Mitogen-activated protein kinases (MAPKs) are correlated with a more
      malignant phenotype in many cancers. This study was designed to evaluate the
      predictive value of the expression of MAPK phosphatase-1 (MKP-1) and
      phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK(1/2)), as the key
      regulatory mechanism of the MAPKs, in lung squamous cell carcinoma (SCC).
      METHODS: We assessed the expressions of MKP-1 and p-ERK(1/2) in twenty subjects
      at different differentiation degree of SCC and five normal lungs by
      immunohistochemistry and real-time reverse transcriptase polymerase chain
      reaction (RT-PCR) analysis. RESULTS: Immunohistochemistry and real-time RT-PCR
      assay showed that the expression of MKP-1 was gradually decreased as tissue type
      went from normal lung tissues to increasingly undifferentiated carcinoma, and it
      was negatively correlated with tumor differentiation (P<0.01). However, the
      expression of p-ERK(1/2) or ERK(1/2) was gradually increased as tissue type went
      from normal lung tissues to increasingly undifferentiated carcinoma, and it was
      positively correlated with tumor differentiation (P<0.01). CONCLUSIONS: Our data
      indicates the relevance of MKP-1 and p-ERK(1/2) in SCC as a potential positive
      and negative prognostic factor. The imbalanced expression of MKP-1 and p-ERK(1/2)
      may play a role in the development of SCC and these two molecules may be new
      targets for the therapy and prognosis of SCC.

PMID- 21960347
TI  - Iptakalim, an ATP-sensitive potassium channel opener, confers neuroprotection
      against cerebral ischemia/reperfusion injury in rats by protecting neurovascular
      unit cells.
AB  - OBJECTIVE: To investigate the role of iptakalim, an ATP-sensitive potassium
      channel opener, in transient cerebral ischemia/reperfusion (I/R) injury and its
      involved mechanisms. METHODS: Intraluminal occlusion of middle cerebral artery
      (MCAO) in a rat model was used to investigate the effect of iptakalim at
      different time points. Infarct volume was measured by staining with 2,3,5
      triphenyltetrazolium chloride, and immunohistochemistry was used to evaluate the
      expressions of Bcl-2 and Bax. In vitro, neurovascular unit (NVU) cells, including
      rat primary cortical neurons, astrocytes, and cerebral microvascular endothelial
      cells, were cultured and underwent oxygen-glucose deprivation (OGD). The
      protective effect of iptakalim on NVU cells was investigated by cell viability
      and injury assessments, which were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide and release of lactate dehydrogenase. Caspase-3, Bcl
      2 and Bax mRNA expressions were evaluated by real-time polymerase chain reaction
      (PCR). RESULTS: Administration of iptakalim 0 or 1 h after reperfusion
      significantly reduced infarct volumes, improved neurological scores, and
      attenuated brain edema after cerebral I/R injury. Iptakalim treatment (0 h after
      reperfusion) also reduced caspase-3 expression and increased the ratio of Bcl-2
      to Bax by immunohistochemistry. Iptakalim inhibited OGD-induced cell death in
      cultured neurons and astrocytes, and lactate dehydrogenase release from cerebral
      microvascular endothelial cells. Iptakalim reduced mRNA expression of caspase-3
      and increased the ratio of Bcl-2 to Bax in NVU cells. CONCLUSIONS: Iptakalim
      confers neuroprotection against cerebral I/R injury by protecting NVU cells via
      inhibiting of apoptosis.

PMID- 21960348
TI  - Evaluation of a risk factor scoring model in screening for undiagnosed diabetes
      in China population.
AB  - OBJECTIVE: To develop a risk scoring model for screening for undiagnosed type 2
      diabetes in Chinese population. METHODS: A total of 5348 subjects from two
      districts of Jinan City, Shandong Province, China were enrolled. Group A (2985)
      included individuals from east of the city and Group B (2363) from west of the
      city. Screening questionnaires and a standard oral glucose tolerance test (OGTT)
      were completed by all subjects. Based on the stepwise logistic regression
      analysis of Group A, variables were selected to establish the risk scoring model.
      The validity and effectiveness of this model were evaluated in Group B. RESULTS:
      Based on stepwise logistic regression analysis performed with data of Group A,
      variables including age, body mass index (BMI), waist-to-hip ratio (WHR),
      systolic pressure, diastolic pressure, heart rate, family history of diabetes,
      and history of high glucose were accepted into the risk scoring model. The risk
      for having diabetes increased along with aggregate scores. When Youden index was
      closest to 1, the optimal cutoff value was set up at 51. At this point, the
      diabetes risk scoring model could identify diabetes patients with a sensitivity
      of 83.3% and a specificity of 66.5%, making the positive predictive value 12.83%
      and negative predictive value 98.53%. We compared our model with the Finnish and
      Danish model and concluded that our model has superior validity in Chinese
      population. CONCLUSIONS: Our diabetes risk scoring model has satisfactory
      sensitivity and specificity for identifying undiagnosed diabetes in our
      population, which might be a simple and practical tool suitable for massive
      diabetes screening.

PMID- 21960349
TI  - Ototoxic destruction by co-administration of kanamycin and ethacrynic acid in
      rats.
AB  - It is well known that ethacrynic acid (EA) can potentiate the ototoxicity of
      aminoglycoside antibiotics (AmAn) such as kanamycin (KM), if they were applied at
      the same time. Currently, to create the model of EA-KM-induced cochlear lesion in
      rats, adult rats received a single injection of EA (75 mg/kg, intravenous
      injection), or followed immediately by KM (500 mg/kg, intramuscular injection).
      The hearing function was assessed by auditory brainstem response (ABR)
      measurement in response to click and/or tone bursts at 4, 8, 12, 16, 20, 24, and
      32 kHz. The static microcirculation status in the stria vascularis after a single
      EA injection was evaluated with eosin staining. The pathological changes in
      cochlear and vestibular hair cells were also quantified after co-administration
      of EA and KM. After a single EA injection, blood flow in vessels supplying the
      stria vascularis rapidly diminished. However, the blood supply to the cochlear
      lateral wall partially recovered 5 h after EA treatment. Threshold changes in ABR
      were basically parallel to the microcirculation changes in stria vascularis after
      single EA treatment. Importantly, disposable co-administration of EA and KM
      resulted in a permanent hearing loss and severe damage to the cochlear hair
      cells, but spared the vestibular hair cells. Since the cochlear lateral wall is
      the important part of the blood-cochlea barrier, EA-induced anoxic damage to the
      epithelium of stria vascularis may enhance the entry of KM to the cochlea. Thus,
      experimental animal model of selective cochlear damage with normal vestibular
      systems can be reliably created through co-administration of EA and KM.

PMID- 21960350
TI  - Transumbilical single-port laparoscopic cholecystectomy using traditional
      laparoscopic instruments: a report of thirty-six cases.
AB  - OBJECTIVE: To evaluate the feasibility and safety of the operation of
      transumbilical single-port laparoscopic cholecystectomy (TSPLC) by traditional
      laparoscopic instruments and summarize the initial experience. METHODS: Sixty
      subjects with cholelithiasis were divided into two groups. One group (36 cases)
      underwent TSPLC and the control group (24 cases) underwent traditional three-port
      laparoscopic cholecystectomy (LC). Postoperative complications were observed and
      operation time, hospital days, visual analogue scale (VAS) after 6 and 24 h of
      operation, and subject satisfaction score were measured. RESULTS: TSPLC and
      traditional LC were performed successfully in the two groups. The operation time
      in the TSPLC group was significantly longer than that in the control group. There
      was no statistically significant difference in hospital stay and VAS between the
      TSPLC and control groups. The subject satisfaction score in the TSPLC group was
      91.2, significantly higher than that in the control group (P<0.01). All subjects
      recovered from the operation and no postoperative complication occurred during
      the period of two weeks after operation. CONCLUSIONS: TSPLC is a feasible and
      safe method for cholecystectomy, although it may be more time-consuming. However,
      it is welcomed by patients who are more concerned with cosmetic outcomes. Future
      studies are needed to confirm its disadvantages and contraindications.

PMID- 21960351
TI  - Prolonged hypervolemic hemodilution decreases functional capillary density of
      ileal mucosa in pigs revealed by sidestream dark-field imaging.
AB  - OBJECTIVE: Hemodilution changes the physical properties of blood by reducing its
      hematocrit and blood viscosity. We tested whether prolonged hypervolemic
      hemodilution (HHD) impairs functional capillary density (FCD) of ileal mucosa in
      healthy mechanically-ventilated pigs and if there is any correlation between
      changes in FCD of ileal and sublingual mucosas during HHD. METHODS: Sixteen
      domestic female pigs were anesthetized, mechanically-ventilated, and randomly
      assigned to the HHD (20 ml/(kg?h) Hartmann's solution for 3 h) or fluid
      restrictive (5 ml/(kg?h) Hartmann's solution for 3 h) group. Microcirculations of
      sublingual and ileal mucosas via ileostomy were visualized using sidestream dark
      field (SDF) imaging at baseline conditions (t=0 h) and at selected time intervals
      of fluid therapy (t=1, 2, and 3 h). RESULTS: A significant decrease of ileal FCD
      (285 (278-292) cm/cm(2)) in the HHD group was observed after the third hour of
      HHD when compared to the baseline (360 (350-370) cm/cm(2)) (P<0.01). This trend
      was not observed in the restrictive group, where the ileal mucosa FCD was
      significantly higher after the third hour of fluid therapy as compared to the HHD
      group (P<0.01). No correlation between microhemodynamic parameters obtained from
      sublingual and ileal mucosas was found throughout the study. CONCLUSIONS:
      Prolonged HHD established by crystalloid solution significantly decreased ileal
      villus FCD when compared to restrictive fluid regimen. An inappropriate degree of
      HHD can be harmful during uncomplicated abdominal surgery.

PMID- 21960353
TI  - Scope of the organocatalysed asymmetric reductive amination of ketones with
      trichlorosilane.
AB  - A highly active organocatalyst has been shown to affect the asymmetric reductive
      amination of ketones producing both aromatic and aliphatic amines. At 1 mol%
      catalyst loading, a series of structurally diverse chiral amines were quickly and
      economically prepared with good enantioselectivity and generally useful yield.
      The efficient synthesis of the calcimimetic (+)-NPS R-568 (67%, 89% ee)
      demonstrated the synthetic applicability of this methodology.

PMID- 21960354
TI  - Impact of intensive physical activity on selenium status.
AB  - Various biomarkers were used to assess selenium (Se) status during 3 months of
      basic military training in a group of recruits. Samples of whole blood and plasma
      or serum were taken from a group of conscripts three times: at the beginning (n =
      15), in the middle immediately after a severely stressful physical activity (n =
      15) and at the end of military training (n = 13). Selenium was determined in diet
      samples, blood, plasma and plasma protein fractions as selenoprotein P (SelP) and
      glutathione peroxidase (eGPx). Selenium was determined by hydride generation
      atomic fluorescence spectrometry and fractionation of proteins performed by
      affinity chromatography. Total serum glutathione, erythrocyte and serum GPx
      activity were followed as well. The average Se intake was calculated according to
      meal consumption questionnaires and Se determined in composite diet samples,
      giving an assessed intake of 48 +/- 10 MUg/day. At all three samplings, the
      average blood Se concentration was within the framework of adequate supply (87 +/
      12, 94 +/- 15 and 80 +/- 13 ng/g). Plasma Se was between 70 and 80 ng/g (71 +/-
      10, 79 +/- 9 and 76 +/- 10 ng/g), which is believed to enable the full expression
      of plasma GPx. The average shares of plasma Se proteins were 61 +/- 6%, 58 +/- 6%
      and 54 +/- 9% for SelP and 27 +/- 4%, 34 +/- 7% and 29 +/- 5% for GPx. Although
      the observed tendency of the increases of serum and erythrocyte GPx activities at
      the second and third samplings with respect to the first was statistically
      insignificant, it is still indicative of some protection against oxidative
      stress, while the decreasing SelP levels during training suggest a slowly
      decreasing biologically active selenium pool.

PMID- 21960355
TI  - Dietary vanadium induces lymphocyte apoptosis in the bursa of Fabricius of
      broilers.
AB  - The purpose of this 42-day study was to investigate the apoptosis in the bursa of
      Fabricius induced by different levels of dietary vanadium. A total of 420 1-day
      old avian broilers were divided into 6 groups in which there were 7 replicates in
      each group and 10 broilers in each replicate and fed on a corn-soybean basal diet
      as control diet (vanadium 0.073 mg/kg) or the same diet amended to contain 5, 15,
      30, 45, and 60 mg/kg vanadium supplied as ammonium metavanadate (NH(4)VO(3)).
      Ultrastructurally, mitochondrial injury and increased numbers of apoptotic cells
      with condensed nuclei were observed in the 30, 45, and 60 mg/kg groups. As
      measured by flow cytometry, the percentages of apoptotic lymphocytes were
      significantly increased in the 15-, 30-, 45-, and 60-mg/kg groups when compared
      with those of control group. Meanwhile, the terminal deoxynucleotidyl transferase
      2'-deoxyuridine 5'-triphosphate nick end-labeling assay showed that there were
      increased numbers of apoptotic cells in the 30-, 45-, and 60-mg/kg groups.
      Immunohistochemical tests showed increased numbers of positive cells under Bax
      and caspase-3 protein detection and decreased Bcl-2 protein in the 15-, 30-, 45-,
      and 60-mg/kg groups. The vanadium content of the bursa was found to be
      significantly increased in the 30-, 45-, and 60-mg/kg groups. These results
      suggested that dietary vanadium in excess of 15 mg/kg could cause lymphocyte
      apoptosis in the bursa of Fabricius and impact humoral immunity in broilers.
      Lymphocyte apoptosis in the bursa induced by high levels of dietary vanadium is
      associated with mitochondrial injury and changes in levels of apoptogenic
      proteins, such as Bcl-2, Bax, and caspase-3.

PMID- 21960356
TI  - Detailed dosimetric evaluation of intensity-modulated radiation therapy plans
      created for stage C prostate cancer based on a planning protocol.
AB  - BACKGROUND: Intensity-modulated radiation therapy (IMRT) has been employed as a
      precision radiation therapy with higher conformity to the target. Although
      clinical outcomes have been reported for many investigations, detailed treatment
      planning results have not been mentioned to date. The aim of this study was to
      evaluate the dose specifications of our IMRT treatment plans for locally advanced
      prostate cancer. METHODS: Seventy-seven clinically applied IMRT plans treated
      between September 2003 and December 2005, in which patients were irradiated with
      78 Gy in the prone position, were retrospectively analyzed. Dosimetric data
      output from dose volume histograms were evaluated in detail. RESULTS: The mean
      dose +/- standard deviation, homogeneity index, and conformity index to the
      planning target volume (PTV) were 78.3 +/- 0.7 Gy (100.4 +/- 0.9%), 13.7 +/- 3.0,
      and 0.83 +/- 0.04, respectively. For the clinical target volume, the mean dose
      was 80.3 +/- 0.7 Gy (102.9 +/- 0.9%).The V40, V60, and V70 Gy of the rectal wall
      were 58.3 +/- 2.8, 29.6 +/- 2.7, and 15.2 +/- 3.0%, respectively. Planning
      difficulties were encountered in patients whose bowels were displaced downward,
      as constraints imposed by the bowel position altered the dose index of the PTV.
      In many cases, additional bowel optimization parameters were required to satisfy
      constraints for organs at risk. However, major deviation could be avoided by
      inverse planning with computer optimization. CONCLUSION: IMRT allowed the
      creation of acceptable and practical treatment plans for locally advanced
      prostate cancer. Reports regarding detailed dosimetric evaluations are mandatory
      for interpreting clinical outcomes in the future.

PMID- 21960357
TI  - Analyzing proteasomal subunit expression reveals Rpt4 as a prognostic marker in
      stage II colorectal cancer.
AB  - Colorectal cancer is a leading cause of cancer-related deaths worldwide. Early
      diagnosis and treatment of colorectal cancer is the key to improving survival
      rates and as such a need exists to identify patients who may benefit from
      adjuvant chemotherapy. The dysregulation of the ubiquitin-proteasome system (UPS)
      has been implicated in oncogenesis and cancer cell survival, and proteasome
      inhibitors are in clinical use for a number of malignancies including multiple
      myeloma. In our study, we examined the protein expression of several key
      components of the UPS in colorectal cancer using immunohistochemistry to
      determine expression levels of ubiquitinylated proteins and the proteasomal
      subunits, 20S core and Rpt4 in a cohort of 228 patients with colon cancer.
      Multivariate Cox analysis revealed that neither the intensity of either
      ubiquitinylated proteins or the 20S core was predictive in either Stage II or III
      colon cancer for disease free survival or overall survival. In contrast, in Stage
      II patients increased Rpt4 staining was significantly associated with disease
      free survival (Cox proportional hazard ratio 0.605; p = 0.0217). Our data suggest
      that Rpt4 is an independent prognostic variable for Stage II colorectal cancer
      and may aid in the decision of which patients undergo adjuvant chemotherapy.

PMID- 21960358
TI  - [Drug resistance testing of Mycobacterium tuberculosis isolates from sputum in
      Chad].
AB  - Culture and resistance testing of Mycobacterium tuberculosis are not regularly
      performed in Chad. Sputa were obtained from three different categories of
      hospitals (district, regional and national) in Chad. All examined sputa were
      smear-positive and were investigated by culture and drug resistance testing for
      first-line antituberculosis drugs. From 232 sputa positive for acid-fast bacilli,
      135 isolates of M. tuberculosis from different patients (46 women, 89 men, mean
      age 34 years) were analyzed. All the patients except one corresponded to new
      cases of tuberculosis. In total, 27 out of 135 isolates (20%) were resistant to
      at least one major antituberculosis drug. Resistance to isoniazid was the most
      frequent resistance observed, with 18 isolates (13%) presenting at least this
      resistance. Three isolates (2.2%) were resistant to isoniazid and rifampicin
      (multidrug resistance MDR) including one isolate being concomitantly resistant to
      streptomycin and ethambutol. The resistance rate differed in relation to the
      category of the hospital; the most important resistance rate was observed in
      regional hospitals (33%), while it was 16% and 14% in the national and district
      hospitals, respectively. HIV serology was performed in 81 patients, among whom 20
      (25%) were positive. This is the first study that shows that drug resistance of
      M. tuberculosis is present in Chad. Besides single drug-resistant isolates,
      multidrug-resistant strains of M. tuberculosis could also be identified. This
      result highlights the urgency of initiating actions to detect drug resistance and
      limit the spread of drug-resistant strains.

PMID- 21960359
TI  - Validity, reliability, and feasibility of a quality of life questionnaire for
      people with dementia.
AB  - The present study investigates the validity, reliability, and applicability of
      the German version of the QUALIDEM, which is used to measure the quality of life
      of people with dementia in nursing homes. The sample consists of data from 203
      people (average age 84 +/- 9 years, 74% female) with mild to moderate dementia
      and 283 persons (average age 86 +/- 8 years, 79% female) with severe to very
      severe dementia. These are baseline data from two lighthouse projects on dementia
      (STI-D and InDemA). The investigation of the feasibility is based on four expert
      interviews. The construct validity of the 37-item version of the QUALIDEM shown
      by the factors satisfied behavior, unapproachable and unsatisfied behavior,
      positive self-image, negative affect, social relations, feeling at home, restless
      tense behavior, and having something to do were identified. Furthermore, for the
      18-item version the following four factors were computed: satisfied behavior,
      unapproachable and unsatisfied behavior, restless tense behavior, and negative
      affect. Cronbach's alpha values for the determined factors are between 0.64 and
      0.87 (37-item version) and between 0.61 and 0.83 (18-item version), which
      corresponds with a medium to high reliability (internal consistency).
      Furthermore, the student assistants assessed the QUALIDEM as applicable and
      practical.

PMID- 21960360
TI  - [Assessment of balance in community dwelling older adults: reliability and
      validity of the German version of the Fullerton Advanced Balance Scale].
AB  - The purpose of this study was to validate the German translation of the
      originally English Fullerton Advanced Balance Scale (FAB-D). The 10-item test
      battery is a performance-based measure that addresses the multiple dimensions of
      balance. The German FAB-D using a forward-backward procedure was examined by a
      sample of n = 96 community dwelling older adults (71,6 +/- 7,5 years of age) who
      had reported no history of a fall in the previous 6 months (non-fallers) and 66
      older adults (age 75,3 +/- 7,3 years of age) who reported falling one or more
      times (recurrent fallers). The following internationally accepted instruments
      were used for validation: The Berg-Balance-Scale (BBS), the Activities-Specific
      Balance Confidence (ABC-D) scale, the Short Form Health Survey (SF-36), the
      Physical Activity Scale for the Elderly (PASE), the Trail-Making-Test (TMT), and
      motor tests (balance, strength, mobility). Explorative and confirmative factor
      analysis showed the best fit for a one dimensional solution. Cronbach's alpha of
      the German version of the FAB-D was 0.988. Test-retest reliability for the total
      score was 0.965 and ranged from 0.86-0.88 for individual items. The scales
      correlate with convergent measures assessing postural control and falls-related
      confidence (BBS, r = 0.685; Timed-Up-and-Go-Test, r = -0.632; ABC-D, r = 0.561).
      Criterion validity of the FAB-D was established by statistically significant
      correlations between the total scale, and the subdimensions of the SF-36
      (physical 0.52, mental 0.38), the PASE (0.29), the TMT A (-0.30) and B (-0.41),
      the Chair Rising Test (0.59) and the 10 m walk (normal velocity -0.49; fast
      velocity -0.56). Significant differences in the FAB-D scores were found in older
      adults with (30,3 +/- 8,6) and without falls (36,1 +/- 4,2). Older adults with a
      recent fall history scored lower on the FAB-D than older adults without a recent
      fall history. To conclude, the German version of the FAB-D has properties
      analogous to the original English version and is apparently useful in assessing
      the multiple dimensions of balance in community dwelling older adults.

PMID- 21960361
TI  - A study on the waste metal remediation using floriculture at East Calcutta
      Wetlands, a Ramsar site in India.
AB  - Use of specific plant species in remediation of heavy metal-contaminated soil and
      water was a promising eco-friendly technology. The present study indicated the
      possibilities of phytoremediation of metal-contaminated (namely Ca, Cr, Mn, Fe,
      Cu, Zn, and Pb) soil by using plant species important for floriculture of East
      Calcutta Wetlands, a Ramsar site at the eastern fringe of Calcutta city. Plant
      species like sunflower (Helianthus annuus), marigold (Tagetes patula), and cock's
      comb (Celocia cristata) grew on soil contaminated by industrial sludge and
      irrigated regularly with wastewater accumulated different metals in different
      plant parts in varied concentrations. Pot culture study in the laboratory setup
      was also done to ascertain the efficiency of these plants for ameliorating
      contaminated soil. It was found that general accumulation patterns of metals
      concerned in different plant parts were root > leaf > stem > flower. This work
      indicated the importance of cultivation of economically important, non-edible,
      ornamental plant species as an alternative cost-effective practice to remediate
      heavily contaminated farmlands of East Calcutta Wetlands.

PMID- 21960362
TI  - Assessment of the effects of urbanization on trace elements of toe bones.
AB  - Amphibians, particularly frogs and toads, are increasingly used as bioindicators
      of contaminant accumulation in pollution studies. We developed an analytical
      technique to analyse their elemental contents based on a small amount of toe bone
      samples. This method is environment-friendly as, unlike traditional methods, it
      is not necessary to kill animals during sampling. Using this technique, we
      explored the effects of urbanization on the elemental contents of toe bones. Bufo
      bufo specimens were collected from an urban and two rural ponds. The ratios of Ca
      and P at the ponds were: 20.5% Ca and 14.6% P at the urban pond and 30.4% and
      29.6% Ca, 22.4% and 21.7% P at the rural ponds, respectively. For the other
      elements, the following percentage ratios were found: 0.7% B, 0.3% Mg and 0.06%
      Zn at the urban pond and 1.1% and 0.4% B, 0.4% Mg and 0.05% Zn at the rural
      ponds, respectively. Canonical discriminant analysis indicated the separation of
      the urban and the rural ponds based on the elemental concentrations of toe bones.
      Significant differences were found between the concentrations of Ca, P, Mg, B and
      Zn at the urban and the rural ponds (p < 0.05). Anthropogenic activity was found
      to have effects on the elemental contents of toe bones in the urbanized area. Our
      study also demonstrated that the developed method was appropriate for the
      elemental analysis of small samples to assess the effects of urbanization.

PMID- 21960363
TI  - Contamination by polychlorinated biphenyls (PCBs) in striped dolphins (Stenella
      coeruleoalba) from the Southeastern Mediterranean Sea.
AB  - Concentrations of polychlorinated biphenyls (PCBs) including dioxin-like PCBs
      (non-ortho, PCB 77, PCB 126, and PCB 169 and mono-ortho, PCB 105, PCB 118, and
      PCB 156) were measured in different organs and tissues (melon, blubber, liver,
      kidney, lung, heart, and muscle tissue) of striped dolphins (Stenella
      coeruleoalba) from the Eastern Mediterranean Sea (Adriatic Sea). The mean highest
      levels were in blubber and melon, followed by liver, kidney, lung, heart, and
      muscle tissue. PCB profiles were similar in all tissues and organs being
      dominated by the higher chlorinated homologues (hexa-CBs, 55.8-62.1%; penta-CBs,
      15.4-20.0%; and hepta-CB PCB 180, 12.7-16.5%). Major PCBs in all tissues were
      congeners 138 and 153 collectively accounting for 50.6-58.3% of the total PCB
      concentrations, followed by PCB 101, 105, 118, and 180 constituting from 27.0% to
      31.0%. PCB levels were higher in adult males than in adult females. The estimated
      2,3,7,8-TCDD toxic equivalents of non- and mono-ortho PCBs were much higher than
      the threshold level above which adverse effects have been observed in other
      marine mammals species, suggesting that striped dolphins in this region are at
      risk for toxic effects.

PMID- 21960364
TI  - Research on the alternatives in a strategic environmental assessment based on the
      extension theory.
AB  - The main purpose of a strategic environmental assessment (SEA) is to facilitate
      the early consideration of potential environmental impacts in decision-making
      processes. SEA alternative identification is a core issue within the SEA
      framework. However, the current methods of SEA alternative formulation and
      selection are constrained by the limited setting range and lack of scientific
      evaluation. Thus, the current paper attempts to provide a new methodology based
      on the extension theory to identify a range of alternatives and screen the best
      one. Extension planning is applied to formulate a set of alternatives that
      satisfy the reasonable interests of the stakeholders. Extension priority
      evaluation is used to assess and optimize the alternatives and present a
      scientific methodology for the SEA alternative study. Thereafter, the urban
      traffic plan of Dalian City is used as an example to demonstrate the feasibility
      of the new method. The traffic planning scheme and the environmental protection
      scheme are organically combined based on the extension theory, and the
      reliability and practicality of this approach are examined.

PMID- 21960365
TI  - Promoter methylation-mediated inactivation of PCDH10 in acute lymphoblastic
      leukemia contributes to chemotherapy resistance.
AB  - PCDH10 has been implicated as a tumor suppressor, since epigenetic alterations of
      this gene have been noted in multiple tumor types. However, to date, studies
      regarding its role in acute and chronic leukemias are lacking. Here, we have
      investigated the presence of promoter hypermethylation of two CpG islands of the
      PCDH10 gene by methylation-specific PCR in 215 cases of various subsets of
      myeloid- and lymphoid-lineage leukemias. We found that PCDH10 promoter
      hypermethylation was frequent in both B-cell (81.9%) and T-cell (80%) acute
      lymphoblastic leukemia (ALL), while it was present in low frequency in most
      subtypes of myeloid leukemias (25.9%) and rare in chronic myeloid leukemia
      (2.2%). PCDH10 expression was downregulated via promoter hypermethylation in
      primary ALL samples (N = 4) and leukemia cell lines (N = 11). The transcriptional
      repression caused by PCDH10 methylation could be restored by pharmacologic
      inhibition of DNA methyltransferases. ALL cell lines harboring methylation
      mediated inactivation of PCDH10 were less sensitive to commonly used leukemia
      specific drugs suggesting that PCDH10 methylation might serve as a biomarker of
      chemotherapy response. Our results demonstrate that PCDH10 is a target of
      epigenetic silencing in ALL, a phenomenon that may impact lymphoid-lineage
      leukemogenesis, serve as an indicator of drug resistance and may also have
      potential implications for targeted epigenetic therapy.

PMID- 21960366
TI  - A diagonal approach to chemical recycling of carbon dioxide: organocatalytic
      transformation for the reductive functionalization of CO2.

PMID- 21960367
TI  - Simultaneous determination of nine endogenous steroids in human urine by
      polymeric-mixed micelle capillary electrophoresis.
AB  - A new CE system based on the use of polymeric-mixed micelles (cholic acid, SDS
      and the poloxamine Tetronic((r)) 1107) was developed for the simultaneous
      determination of nine steroids in human urine. This method allows the baseline
      separation and quantitation of cortisol, androstenedione, estriol,
      dehydroepiandrosterone sulfate, testosterone, dehydroepiandrosterone, estrone,
      progesterone and estradiol in less than 25 min showing to be sensitive enough to
      detect low concentrations of these steroids in urine samples (5-45 ng/mL). The
      optimized electrophoretic conditions were performed using a 50 cm * 75 MUm
      capillary, 18 kV, 25 degrees C, with 44 mM cholic acid, 10 mM SDS, 0.05% w/v
      tetronic((r)) 1107, 2.5% v/v methanol, 2.5% v/v tetrahydrofuran in 5 mM borate -
      5 mM phosphate buffer (pH=8.0) as a background electrolyte and a dual 210/254 UV
      detection. The method can simultaneously determine 0.1-120 MUg/mL, which
      corresponds to 5-6000 ng/mL of steroids in 2 mL urine. The recoveries ranged
      between 82.4 and 101.5%. Due to its simplicity, speed, accuracy and reliability,
      the proposed method could be a potential alternative to the traditional
      methodologies used with clinical purposes.

PMID- 21960368
TI  - The reliability of prayer-based self-efficacy scale to assess self-confidence of
      Muslims with low back pain.
AB  - BACKGROUND: Low back pain (LBP) may challenge an individual's self-confidence to
      perform usual daily activities such as Islamic daily prayer. Existing self
      efficacy scales may not be appropriate to assess individual's self-confidence to
      perform Islamic prayers. OBJECTIVE: This study aimed to develop a scale to assess
      self-confidence to prepare and perform Islamic prayer in the presence of LBP, the
      Islamic Prayer-based Self-efficacy Scale (IpbSeS), and to determine its
      consistency. METHODS: The IpbSeS consists of three parts: pre-prayer preparation,
      getting to and from the mosque, and positions and movements during prayer. On a
      scale of 0 to 6, 0 indicates 'not at all confident' and 6 'fully confident'.
      Sixty individuals with LBP gave their responses on two different visits. Pain
      intensity was assessed by the Visual Analogue Scale (VAS), and the pain intensity
      changes were assessed using a seven-point global patient rating scale. DATA
      ANALYSIS: Descriptive statistics, Pearson's correlation coefficient, Wilcoxon
      test and t-test were used in the analysis (alpha set at 0.05). RESULTS: VAS
      scores did not differ significantly between visits. No association was found
      between VAS and age (r = 0.039, p = 0.77) and between VAS and body mass index
      (BMI; r = 0.06, p = 0. 67). All 28 questions have consistent responses on two
      visits (0.75 <= r <= 0.99, p < 0.001 for all) indicating a very high reliability.
      CONCLUSION: IpbSeS appears to be a reliable instrument to assess the self
      confidence of Muslims in the presence of LBP to pray.

PMID- 21960370
TI  - Prevalence and risk factors of sleep disturbance in continuous ambulatory
      peritoneal dialysis patients in Guangzhou, southern China.
AB  - PURPOSE: Sleep disturbance is significantly associated with overall morbidity,
      mortality, and quality of life in end-stage renal disease patients. Although it
      was reported that the prevalence of poor sleep quality was 41-83% in hemodialysis
      patients, sleep disturbance was not well understood in peritoneal dialysis (PD)
      patients, especially in Asian PD patients. The present study attempted to assess
      the prevalence and related risk factors of sleep disturbance among continuous
      ambulatory peritoneal dialysis (CAPD) patients in Guangzhou, southern China.
      METHODS: Pittsburgh Sleep Quality Index (PSQI) was used to assess the sleep
      quality in eligible 212 CAPD patients (53.3% men), average age 49.9 +/- 16.7
      years. RESULTS: The average global PSQI score of the CAPD patients was 9.5 +/-
      5.2, with 171 (80.4%) poor sleepers (PSQI scores > or = 5). The PSQI score was
      negatively correlated with serum albumin (r = -0.21, P = 0.003) subjective global
      assessment (SGA) score (r = -0.27, P = 0.001) and positively correlated with age
      (r = 0.34, P < 0.001), high-sensitivity C-reactive protein (r = 0.20, P = 0.008),
      level of calcium * phosphate product (r = 0.19, P = 0.009), cardiovascular
      disease (r = 0.17, P = 0.019), Charlson comorbidity index score (r = 0.21, P =
      0.004), malnutrition-inflammation score (MIS) (r = 0.31, P < 0.001), and duration
      on CAPD (r = 0.20, P = 0.005). In multiple analysis, old age, high calcium *
      phosphate product, low SGA score (beta = -0.23, P = 0.042), and high MIS (beta =
      0.30, P = 0.007) were independent predictors of sleep disturbance in CAPD
      patients. CONCLUSION: We clearly demonstrated the novel relationship of
      malnutrition and calcium * phosphate product with poor sleep quality in CAPD
      patients, which may be a part of the explanation for the strong links between
      sleep quality and overall morbidity and mortality.

PMID- 21960369
TI  - Evaluation of the impact of a new synthetic vitamin E-bonded membrane on anemia
      and rHuEPO requirement in ESRD patients with central venous catheters: a pilot
      study.
AB  - In the last years, the number of hemodialysis (HD) patients with erythropoietin
      (rHuEPO) resistance is increasing. Probably, central venous catheters (CVCs)
      contribute to this resistance by inducing inflammation and oxidative stress. This
      study was aimed to compare vitamin E-bonded dialyzer (PSVE) versus
      polyethersulfone membrane. Sixteen subjects with CVCs were included in a
      prospective two-arm crossover 12-month study. The primary endpoints were the
      rHuEPO requirement and the erythropoiesis-stimulating agents (ESA) index, which
      was defined by the ratio between weekly EPO dosage (IU/kg/week) and Hb levels
      (g/dl). The mean dosages of rHuEPO to maintain hemoglobin between 10.5 and 12
      g/dl were 135 +/- 59 and 101 +/- 57 IU/kg/week with polysulfone and PSVE,
      respectively (P = 0.14). The ESA indexes were 12.1 +/- 5.2 and 8.7 +/- 5.2 (P <
      0.0001) with polysulfone and PSVE, respectively. A trend towards consensual
      changes in protein glycoxidation, antioxidant, and inflammatory markers was
      observed. In conclusion, the study suggests a role for PSVE in the reduction of
      ESA index in HD patients with CVCs.

PMID- 21960371
TI  - Stenting or not prior to extracorporeal shockwave lithotripsy for ureteral
      stones? Results of a prospective randomized study.
AB  - PURPOSE: To determine the need for pre-treatment stenting in patients undergoing
      extracorporeal shockwave lithotripsy (ESWL) for ureteral stones sized 4-10 mm.
      METHODS: A prospective randomized study was conducted between September 2009 and
      March 2011. Included 156 patients randomized in stented and non-stented groups
      and underwent a maximum of 3 ESWL sessions. Radiographic follow-up was used to
      assess the stone fragmentation and clearance. Results were compared in terms of
      stone-free rates, post-treatment morbidity and complications. RESULTS: Overall
      efficacy was 76.9%. Stone-free rates were statistically significantly lower (P =
      0.026) in the stented group (68.6%) compared to the non-stented ones (83.7%).
      Furthermore, stenting was significantly correlated with post-treatment lower
      urinary tract symptoms (P <= 0.001), need for more ESWL sessions (P = 0.019) and
      possibility for operation due to ESWL failure (P = 0.026). A multivariate
      analysis was conducted to identify the parameters which may predict complete
      stone removal after ESWL. Stone size (P = 0.026), stone location (P = 0.011) and
      stenting (P = 0.007) were the most significant factors. CONCLUSIONS: ESWL is an
      efficient and safe treatment for 4- to 10-mm ureteral stones. Pre-treatment
      stenting is limiting stone-free rates and is significantly influencing post-ESWL
      morbidity and quality of life in a negative manner, while it contributes
      minimally to the prophylaxis of complications.

PMID- 21960372
TI  - [Effects of nutrition on the prevention of cancer].

PMID- 21960373
TI  - [New developments in diagnosis and therapy of prostate cancer--from "active
      surveillance" to robotic-assisted surgery].

PMID- 21960374
TI  - [Psycho-oncology: support for patients and family members (interview by Dr. rer.
      nat. Claudia Bruhn)].

PMID- 21960375
TI  - [Migrant oncology patients: cross-cultural translators required].

PMID- 21960376
TI  - [Cancer pain management: the WHO's analgesic ladder as guideline].

PMID- 21960377
TI  - In vitro generation of mature human osteoclasts.
AB  - Mononuclear precursors of human osteoclasts are found in the CD14(+) monocyte
      fraction of circulating peripheral blood mononuclear cells (PBMCs). It is
      possible to generate osteoclasts in vitro from PBMCs cultured with macrophage
      colony-stimulating factor and receptor activator for nuclear factor kappaB
      ligand. In these cultures, however, it is not possible to distinguish the effect
      of a specific agent on osteoclast resorption activity as opposed to osteoclast
      differentiation. To produce a population of mature human osteoclasts to study
      osteoclast lacunar resorption specifically, we cultured CD14(+) human monocytes
      on hydrophobic dishes in order to generate and maintain osteoclasts in suspension
      prior to culturing them on coverslips and dentine slices. Multinucleated cells
      formed in these cultures expressed vitronectin receptor, tartrate-resistant acid
      phosphatase, and cathepsin K. These cells also produced F-actin rings and were
      capable of extensive lacunar resorption on dentine slices after 24 h in culture.
      Lacunar resorption was inhibited by calcitonin and zoledronate but not by
      osteoprotegerin. This method of generating a highly enriched population of mature
      human osteoclasts should provide a valuable means of specifically assessing the
      effect of molecular factors (e.g., cytokines, growth factors, hormones) and
      therapeutic agents on osteoclast resorption activity.

PMID- 21960378
TI  - In vitro anthelmintic activity of the essential oils of Zanthoxylum
      zanthoxyloides and Newbouldia laevis against Strongyloides ratti.
AB  - The need for new anthelmintic with no chemical residues is becoming urgent. In a
      program aiming at the evaluation of plant as sources of new active molecules, the
      anthelmintic activities of the essential oils (EOs) obtained from either
      Zanthoxylum zanthoxyloides seeds or Newbouldia laevis leaves were evaluated
      against Strongyloides ratti by analyzing the results of two in vitro bioassays.
      These two plants and their tested parts were retained after an ethnopharmacology
      survey that confirmed their use by small-scale farmers for treatment of small
      ruminants affected by digestive helminths. The plants were harvested in Benin,
      and their EO were obtained by hydrodistillation. The EO yield of extraction was
      0.65% (w/w) of for Z. zanthoxyloides seeds and 0.05% (w/w) for N. laevis. The
      chemical compositions of the two EOs were analyzed by gas chromatography coupled
      with mass spectrometry. The major constituents of the EO from Z. zanthoxyloides
      consisted of the following compounds: gamma-terpinene (18 %), undecane (15 %),
      valencene (8.3 %), decanal (8.3 %), and 3-carene (6.7 %). In contrast, the major
      constituents of the EO from N. laevis leaves consisted of the following
      compounds: beta-caryophyllene (36 %) and eugenol (5.8 %). An egg-hatching
      inhibition (EHI) assay was developed and a larval migration inhibition assay was
      used on S. ratti to examine the effects of the EOs and to evidence their
      inhibitory concentrations (IC(50) and IC(90)) values on this nematode.
      Furthermore, the toxicity of the two EOs on Vero cell line was evaluated. When
      tested on S. ratti egg hatching, the two EOs resulted in similar IC(50) values
      (19.5 and 18.2 MUg/ml for Z. zanthoxyloides and N. laevis, respectively), which
      were about sevenfold higher than that of the control (thiabendazole, IC(50) = 2.5
      MUg/ml). Larval migration was inhibited at similar concentrations for: Z.
      zanthoxyloides (IC(50) = 46 MUg/ml), N. laevis (IC(50) = 51 MUg/ml), and the
      control [levamisole (IC(50) = 36 MUg/ml)]. No cytotoxicity was found on Vero
      cells because both EOs had IC(50) values higher than 50 MUg/ml. Therefore, we
      have concluded that the EOs from two plants, used in folk medicine, may contain
      compounds with anthelmintic activity and could be used as improved traditional
      medicines or, at least, as food additives in a combined treatment for the control
      of helminth infections.

PMID- 21960379
TI  - D-allose and D-psicose reinforce the action of metronidazole on trichomonad.
AB  - The effects of D-allose and D-psicose on Tritrichomonas foetus were examined.
      They were cultured in F-bouillon medium including glucose, but had never
      increased when glucose was substituted to those sugars. When cultured in a medium
      including a dose of ED(50) metronidazole and those sugars, trichomonad density
      was significantly less than that in a medium with metronidazole only. D-Allose
      remarkably reinforced the action of metronidazole. This means there are some
      interactions between metronidazole and those sugars. Although the mechanism is
      not clear, by using those sugars for treatment with metronidazole, the drug
      dosage could be lowered and the development of drug resistance of trichomonad
      parasites might be prevented.

PMID- 21960383
TI  - A new oxime ligand in manganese chemistry: a [Mn8] and a [Mn6] cage from the use
      of 2-dihydroxy-2-phenylacetamidine.
AB  - The use of phamidoxH(2) (phamidoxH(2) = 2-dihydroxy-2-phenylacetamidine) in
      manganese cluster chemistry led to the synthesis and characterization of a
      hexametallic and an octametallic Mn(III) cluster, both of which display a S = 3
      ground state.

PMID- 21960385
TI  - [The effect of social support on the symptoms of depression experienced by
      Portuguese patients with multiple sclerosis].
AB  - INTRODUCTION: The prevalence of depressive symptoms is high among patients with
      multiple sclerosis (MS). Despite being associated with low levels of social
      support, few studies showing the importance of the buffer effect on depressive
      symptoms. The aim is to analyze the effect of social support on depressive
      symptoms. PATIENTS AND METHODS: The sample is composed by 150 MS consecutive
      patients attending the MS Outpatient Clinic of Hospital S. Joao, Porto, that gave
      written consent; illiterate subjects were excluded. The disease parameters, as
      duration, clinical course and disability (Expanded Disability Status Scale) were
      collected in the clinical protocols. In the comparison of socio-demographic
      variables and parameters with the depressive symptoms we used the Mann-Whitney U
      and Kruskal-Wallis H. In interferential analysis we used the MLR with stepwise
      selection of variables. RESULTS: Age, education emotional social support,
      disability, duration of illness and the primary and secondary forms determine
      together 42.4% of depressive symptoms. Gender, marital status, be unskilled
      worker, have material social support and relapsing- remitting form does not
      determine any change in depressive symptoms. CONCLUSIONS: The emotional social
      support is a predictor of depressive symptoms. This study reinforces the need for
      professionals to be sources of social support in promoting programs that reduce
      the risk of depressive symptoms.

PMID- 21960384
TI  - [Clinical features and prognosis of patients with chronic cerebrovascular disease
      (ICBAR study)].
AB  - INTRODUCTION: Patients with cerebrovascular disease (CVD) are a group with a very
      high cardiovascular risk, in addition to that arising from their own vascular
      pathology, probably due to an inadequate control of risk factors and owing to the
      presence of comorbidities. PATIENTS AND METHODS: This research consisted in a
      multi-centre study involving the collaboration of 34 primary care physicians and
      recording of the features of 473 patients with a previous history of a CVD event
      that required hospitalisation. After a clinical follow-up of the cohort, hospital
      readmissions, mortality and causes were analysed. RESULTS: The mean age of
      patients (52% males) was 75 +/- 10 years and the most prevalent risk factors were
      arterial hypertension (79%), dyslipidaemia (66%), obesity (43%) and diabetes
      (29%). Sixty-eight per cent of patients had been diagnosed with stroke and 32%
      with transient ischaemic attack. The mean amount of time elapsed since the first
      CVD event was 6.6 +/- 5.5 years. Twenty-nine per cent of patients had a situation
      of dependence and only one third showed good blood pressure and lipid control.
      During a follow-up lasting 8.2 +/- 2.3 months, 7.2% of patients suffered some
      kind of cardio-vascular event (death or hospitalisation), which independent
      determinants were found to be previous heart failure (hazard ratio, HR = 2.74;
      95% confidence interval, CI 95% = 1.3-5.9); cardiomyopathy (HR = 3.32; CI 95% =
      1.4-8.2); anaemia (HR = 3.09; CI 95% = 1.6-6.2); renal failure (HR = 2.4; CI 95%
      = 1.0-5.6); the situation of dependence (HR = 2.57; CI 95% = 1.3-5.7) and
      cardiovascular admissions over the past year (HR = 3.05; CI 95% = 1.5-5.6).
      CONCLUSIONS: Patients with CVD followed up in the area of primary care present a
      high prevalence of arterial hypertension and little is done to control it. Their
      prognosis is conditioned by cardiovascular comorbidities and sequelae of their
      cerebro-vascular disease.

PMID- 21960386
TI  - [Value of the cutaneous-plantar reflex in the diagnosis of idiopathic carpal
      tunnel syndrome].
AB  - INTRODUCTION: Carpal tunnel syndrome (CTS) is the most common of all focal
      neuropathies. Its diagnosis is based on a neurophysiological study of the thick
      motor and sensory fibres in patients with a characteristic clinical picture,
      although sometimes, in mild cases, this study does not detect the abnormalities.
      The decision was made to evaluate the small-calibre sympathetic fibres by means
      of cutaneous-plantar reflex (CPR) in patients with different degrees of
      idiopathic CTS. SUBJECTS AND METHODS: The study involved 54 cases -15 males and
      39 females with CTS- and 15 healthy volunteer controls. The cases were divided
      into three groups: those with only positive clinical features; those with
      clinical features and alteration of sensory conduction; and those with clinical
      features, alteration of sensory and motor conduction, and axonal loss. The CPR
      was obtained by means of the usual technique (which we modified), involving
      stimulation of the median nerve in the wrist and recording the response in the
      contralateral hand. Two successive responses were processed with an interval of
      more than one minute between them. Special attention was paid to controlling the
      baseline and sweating. A descriptive statistical inference and correlation
      analysis was performed. RESULTS: A decrease in amplitude of the response was
      observed in patients with CTS, with shorter latencies in women and a good
      correlation between the latencies of the first and the second response. No
      significant differences were observed in the other parameters that were studied.
      CONCLUSION: Studying the CPR can provide complementary data in the evaluation of
      CTS.

PMID- 21960387
TI  - [Menstrual headache: subtypes, clinical phenotypes and treatment].
AB  - INTRODUCTION: Up to 60% of women relate their episodes of headache to menstrual
      cycle. Menstrual migraine has been included in the second edition of the
      International Classification of Headache disorders. Menstrual tension-type
      headache has not yet been recognised by the International Headache Society. AIMS:
      To evaluate the prevalence of different subtypes of menstrual headache and to
      analyze their clinical features and the treatment prescribed. PATIENTS AND
      METHODS: We prospectively included women attending several neurology outpatient
      clinics, from January to November 2008 whose headache appeared during the
      menstrual period. RESULTS: A total of 108 patients were included during the study
      period. Mean age was 34.8 +/- 8.9 years-old. 29.3% suffered from pure menstrual
      migraine, 58.7% from menstrual related migraine, 4.5% from pure menstrual tension
      type headache and 7.5% from menstrual related tension type headache. CONCLUSIONS:
      Our data suggest that menstrual related tension-type headaches exist with a
      prevalence found about 12%, in our neurology outpatient clinics.

PMID- 21960388
TI  - [Review of the model of vertical gaze control].
AB  - INTRODUCTION: The main structures involved in the control of vertical gaze, both
      saccades, smooth pursuit and oculovestibular reflexes, are the rostral
      interstitial nucleus of medial longitudinal fasciculus, posterior commissure,
      interstitial nucleus of Cajal, oculomotor complex and trochlear nerve nucleus.
      Despite knowing the functions of these nuclei, and their main interconnections,
      afferents and efferents, there is no definitive and contrasted model of vertical
      gaze control in humans. AIM: Through the description of three cases, and as
      described in scientific literature, our aim is to review the models described to
      date. DEVELOPMENT: The control of vertical saccades generates in the rostral
      interstitial nucleus of medial longitudinal fasciculus, projecting to the
      pertinent oculomotor nuclei ipsilaterally for the inferior gaze, and bilaterally
      for the superior gaze. CONCLUSIONS: The double cross-innervation of the nuclei
      responsible for superior gaze, implies that unilateral lesions predominantly
      affect the inferior gaze.

PMID- 21960389
TI  - [A proposal for a protocol of neuropsychological assessment for use in
      addictions].
AB  - INTRODUCTION: Interest in the brain processes involved in establishing,
      maintaining and overcoming addictions has led to the development, in recent
      years, of a number of neurocognitive models with a substantial amount of
      empirical support. However, agreement still needs to be reached regarding the
      clinical evaluation tests that can be administered and the reason for doing so.
      The aim of this work is to outline some of the most useful neuropsychological
      tests for evaluating addicts, as well as the scales of day-to-day symptoms and
      occupational performance tests that have been validated in Spanish for this
      population. DEVELOPMENT: The cognitive sub-processes addressed in this work,
      which have proved to be useful in the syndromic diagnosis of addictions, are
      processing speed, selective and sustained attention, alternating and divided
      attention, attentional amplitude and central executive, memory, cognitive
      flexibility and fluency, response inhibition, planning, abstraction, decision
      making and, lastly, theory of mind. A protocol involving two 50-minute sessions
      is proposed, where the second session is optional depending on the needs and
      suitability in each case. CONCLUSIONS: This protocol offers several important
      advantages for physicians, including systemisation, the possibility of
      replication and convergence among evaluators or delimitation of the sub-processes
      that can be evaluated by sharing the same scheme. Moreover, it can all be carried
      out in sessions that are short enough to allow them to be offered by nearly all
      services that attend to addicts who request treatment.

PMID- 21960391
TI  - [Persistent carotid-vertebrobasilar anastomoses: hypoglossal artery].

PMID- 21960390
TI  - [Image analysis and processing. Fundaments and applications in neurology and
      neurosurgery].
AB  - In recent years, image techniques have transformed the diagnosis in Medicine.
      Nevertheless, they are, by now, far from a widespread clinic and surgical use.
      Beyond the simple picture inspection, DICOM digital files can be explored by
      using image analysis/processing techniques in a better way. In practice,
      clinicians and surgeons usually are limited to 'see' pictures delivered by
      Radiology. However, image analysis/processing techniques allow the 'client'
      (neurologist or neuro-surgeon) to accomplish interactive image visualizations,
      multiplanar or 3D rendering, measurements, pathway visualizations, etc. All these
      tasks, offer a great advantage in diagnosis, surgical planning, teaching and
      investigation. This paper revise the fundaments of image analysis techniques in
      order to emphasize their utility, and to widespread its utilization not in the
      server (Radiological Department) but, principally, in the client side. Some
      examples of cranio-spinal pathologies are presented aiming to these objectives.

PMID- 21960393
TI  - [Posterior reversible leukoencephalopathy and hypercalcemia].

PMID- 21960394
TI  - [Agenesis of the internal carotid artery in a patient with vascular pathology,
      epilepsy and transient global amnesia].

PMID- 21960395
TI  - [Inferior vena cava filter as a feasible strategy for paradoxical ischaemic
      stroke].

PMID- 21960396
TI  - [Intracranial hypotension syndrome: a review of the magnetic resonance findings].

PMID- 21960397
TI  - Bilateral parotid swelling: a radiological review.
AB  - Bilateral parotid swelling is not an uncommon occurrence and may pose a challenge
      for clinicians and radiologists. Numerous causes of bilateral parotid swellings
      have been identified. The purpose of this pictorial review is to display this
      wide array with a focus on multimodality approach.

PMID- 21960398
TI  - Quantitative evaluation of vascularity within cervical lymph nodes using Doppler
      ultrasound in patients with oral cancer: relation to lymph node size.
AB  - OBJECTIVES: The aim of this study was to quantitatively evaluate the relationship
      between vascularity within lymph nodes and lymph node size on Doppler ultrasound
      images of patients with oral cancer. METHODS: A total of 310 lymph nodes (86
      metastatic, 224 benign) from 63 patients with oral cancer were classified into 4
      groups according to their short axis diameters: Group 1, short axis diameters of
      4-5 mm; Group 2, 6-7 mm; Group 3, 8-9 mm; and Group 4, >= 10 mm. Vascular and
      scattering indices of lymph nodes on Doppler ultrasound images were analysed
      quantitatively. The vascular index was defined as the ratio of blood flow area to
      the whole lymph node area and the scattering index was defined as the number of
      isolated blood flow signal units. RESULTS: For metastatic lymph nodes, the
      vascular index was highest in Group 1 and decreased as lymph node size increased.
      The vascular index of benign lymph nodes did not differ significantly among the
      four groups. The vascular index of metastatic lymph nodes was significantly
      higher than that of benign lymph nodes in Group 1. For metastatic lymph nodes,
      the scattering index increased as lymph node size increased and was significantly
      higher than that of benign lymph nodes in Groups 2-4. CONCLUSIONS: An increase in
      vascularity is a characteristic of Doppler ultrasound findings in small
      metastatic lymph nodes. As the metastatic lymph node size increases, blood flow
      signals become scattered, and the scattering index increases.

PMID- 21960399
TI  - Indirect measurement of the temporomandibular joint disc elasticity with magnetic
      resonance imaging.
AB  - OBJECTIVES: The radiological evaluation of the temporomandibular joint (TMJ)
      consists of demonstrating the morphological features of the disc and the condyle
      in closed and open mouth positions using MRI. We aimed to determine elasticity of
      the disc by measuring the amount of elongation during mouth opening. METHODS: The
      study population included 49 patients. Coronal T(1) and multiplane oblique T(2)
      weighted gradient recalled echo sequences were acquired in open and closed mouth
      positions. Biconcave TMJ disc lengths were measured on sagittal oblique images in
      both positions. Elongation ratio (ER) was calculated for each patient. According
      to the findings, TMJs are classified into subgroups: normal (N), dislocated with
      reduction (DWR), pure DWR (p-DWR), DWR with additional findings (DWR-a) and
      dislocated without reduction (DWOR). Statistical analysis was performed using the
      chi(2) test and receiver operating characteristic analysis. RESULTS: Out of 98
      discs, 22 of them were evaluated as N, 60 as DWR (28 p-DWR, 32 DWR-a) and 16 as
      DWOR. There was no significant difference among the disc lengths in three
      subgroups at the closed mouth position (P = 0.15), whereas there was significant
      difference in the open mouth position (P = 0.0001). There was significant
      difference among subgroups as far as ER is concerned (P < 0.05). CONCLUSIONS: ER
      is a strong indicator of elasticity. Compared with the N group, elasticity of the
      disc was not significantly different in the p-DWR group but the disc elasticity
      was very degraded in DWR-a and in DWOR. A negative conversion or one smaller than
      1.4 mm means a compromised disc, although sometimes it will possess normal
      anatomical configurations or signal characteristics.

PMID- 21960400
TI  - Evaluation of two imaging techniques: near-infrared transillumination and dental
      radiographs for the detection of early approximal enamel caries.
AB  - OBJECTIVES: The aim of this paper was to evaluate a transillumination (TI) system
      using near-infrared (NIR) light and bitewing radiographs for the detection of
      early approximal enamel caries lesions. METHODS: Mesiodistal sections of teeth (n
      =  14) were cut with various thicknesses from 1.5 mm to 4.75 mm. Both sides of
      each section were included, 17 approximal surfaces with natural enamel caries and
      11 surfaces considered intact. The approximal surfaces were illuminated by NIR
      light and X-ray. Captured images were analysed by two calibrated specialists in
      radiology, and re-analysed after 6 months using stereomicroscope images as a gold
      standard. RESULTS: The interexaminer reliability (Kappa test statistic) for the
      NIR TI technique showed moderate agreement on first (0.55) and second (0.48)
      evaluation, and low agreement for bitewing radiographs on first (0.26) and second
      (0.32) evaluation. In terms of accuracy, the sensitivity for the NIR TI system
      was 0.88 and the specificity was 0.72. For the bitewing radiographs the
      sensitivity ranged from 0.35 to 0.53 and the specificity ranged from 0.50 to
      0.72. CONCLUSION: In the same samples and conditions tested, NIR TI images showed
      reliability and the enamel caries surfaces were better identified than on dental
      radiographs.

PMID- 21960401
TI  - A false presence of bifid mandibular canals in panoramic radiographs.
AB  - OBJECTIVES: This study was performed in order to verify bifid mandibular canals
      revealed from panoramic radiographic results. METHODS: 1000 panoramic radiographs
      from dental patients and the panorama, cone beam CT (CBCT) and micro-CT from 40
      dry mandibles were examined for bifid mandibular canals. The results were
      confirmed by a stereoscopic and histological examination of the cross-sectioned
      mandibles. RESULTS: The prevalence of bifid canals detected from the panoramic
      radiographs was 0.038. The panoramic radiographs from one dry mandible showed two
      separate radiolucent mandibular canal-like structures delineated by radio-opaque
      lines. However, a stereoscopic and histological examination of a cross-section of
      the mandible showed that only one canal was a true canal containing neurovascular
      bundles: the other was false, reflecting merely a bony trabecular pattern.
      CONCLUSIONS: The presence of bifid mandibular canals determined by panoramic
      radiography should be judged with great caution in relation to dental surgery.

PMID- 21960402
TI  - Dental students' knowledge and attitudes towards cone beam computed tomography in
      Turkey.
AB  - OBJECTIVE: The aim of this study was to evaluate students' knowledge and
      attitudes regarding cone beam CT (CBCT). METHODS: A questionnaire consisting of
      11 questions was given to 472 dental students (280 pre-graduate and 192 post
      graduate) at two institutions located in Ankara, Turkey (Ankara University,
      Faculty of Dentistry, and Gazi University, Faculty of Dentistry). Differences in
      responses by institution, education level and sex were statistically assessed
      with the chi(2) test. RESULTS: Statistical results showed that only 63.3% of
      students had heard of CBCT. Of these, 59.9% said they had learned about CBCT in
      their classes, 31.0% in seminars and 20.9% from the internet; 76.8% felt that
      CBCT was not given adequate coverage in their courses; 69% thought that CBCT
      should be taught as part of their clinical education; 91% thought it essential
      for CBCT to be available at dental faculties; 53.5% believed that the use of CBCT
      would become more widespread in the near future; and 84.9% wished to use CBCT
      technology in their future careers. CONCLUSION: This research suggests that
      efforts should be made to improve students' knowledge base regarding CBCT and
      that the dental school curriculum should devote more curriculum time to this
      promising new technology.

PMID- 21960403
TI  - Reliability of computational measurement of the condyles on digital panoramic
      radiographs.
AB  - OBJECTIVE: The aim of this study was to evaluate the reliability of a
      computational method for assessing three condylar measurements on digital
      panoramic radiographs: condylar height, area and perimeter. METHODS: A computer
      calculation of the area, the perimeter and the height of 34 condyles was
      determined on digital panoramic radiographs taken from 17 patients. The test
      retest precision of measurements calculation was estimated using an intraclass
      correlation coefficient (ICC) and Dahlberg's formula at 2 week intervals on the
      same radiograph to assess intraobserver precision and on two radiographs (RX1 and
      RX2) to assess the radiographic procedure precision. Changes between measurements
      on RX1 and RX2 were estimated using paired t-tests to detect systematic errors.
      RESULTS: Precision of all indices was very high when measurements were made on
      the same radiograph, thus confirming good reliability for the present
      computational measuring method. The precision was lower when two different
      radiographs were compared but was still within an acceptable range of tolerance.
      There were no statistically significant changes in condylar area, perimeter or
      height values between RX1 and RX2. CONCLUSIONS: This study has demonstrated that
      (1) the height of the condyle can be rapidly and reliably assessed using a
      specific computer system directly on digital panoramic radiographs; (2) although
      less reliable, area and perimeter can also be acceptably evaluated; and (3) this
      method has the potential for being routinely used to monitor changes in clinical
      follow-up as well as for research purposes.

PMID- 21960404
TI  - Imaging findings in mandibular primitive neuroectodermal tumour: a report of a
      rare case and review of the literature.
AB  - Primitive neuroectodermal tumours (PNETs) are aggressive undifferentiated tumours
      that occur mainly in the central nervous system (CNS). Reviewing the literature,
      only six cases of primary PNET of the mandible have been reported. These rare
      tumours are usually overlooked in clinical practice. An 18-year-old woman who
      presented with dental caries and left cheek swelling was initially diagnosed with
      facial cellulitis, but the swelling persisted despite adequate intravenous
      antibiotic therapy. Subsequent ultrasound and MR examinations revealed a tumour
      originating from the left mandibular ramus. The ultrasonography-guided
      percutaneous core needle biopsy confirmed the diagnosis of peripheral PNET. The
      radiographic features of mandibular PNETs are similar to those of PNETs in other
      regions, except for haemorrhage, necrosis and calcification. In addition, this is
      the first reported case with sonographic and MR images of this rare tumour, and
      the first case that was diagnosed based on the ultrasonography-guided
      percutaneous core needle biopsy. Using these image characteristics, mandibular
      PNETs can be diagnosed more accurately.

PMID- 21960405
TI  - Early diagnosis of progressive systemic sclerosis (scleroderma) from a panoramic
      view: report of three cases.
AB  - Systemic sclerosis (scleroderma) is a multisystem disease involving the skin,
      lungs, heart, kidneys and gastrointestinal tract. It is probably owing to a
      disorder of the immune system. It may also have some oral manifestations,
      including limited ability to open the mouth, widening of the periodontal ligament
      (PDL) space and mandibular bone resorption. We report here on three asymptomatic
      cases that were referred to our oral and maxillofacial radiology centre for
      another reason, and in which we suspected scleroderma based on the widening of
      the PDL in the panoramic view. The early diagnosis was finally confirmed by
      pathological findings.

PMID- 21960406
TI  - Central mucoepidermoid carcinoma of maxilla with radiographic appearance of mixed
      radiopaque-radiolucent lesion: a case report.
AB  - Mucoepidermoid carcinoma is the most common primary malignancy of the salivary
      glands. Central mucoepidermoid carcinomas are extremely rare in the jaws. Here we
      report a case of a 19-year-old central mucoepidermoid carcinoma in a young female
      patient which was asymptomatic throughout her history and which radiographically
      simulated a fibro-osseous lesion; both features misled the clinical diagnosis. A
      radiographic picture of mixed radiopaque-radiolucent appearance in central
      mucoepidermoid carcinoma is extremely rare. The long duration is also uncommon
      for a malignant lesion. This case report adds a new dimension to the clinical and
      radiographic picture a central mucoepidermoid carcinoma can reveal.

PMID- 21960407
TI  - A comparative study of the accuracy and reliability of multidetector CT and cone
      beam CT in the assessment of dental implant site dimensions.

PMID- 21960410
TI  - Determination of RW3-to-water mass-energy absorption coefficient ratio for
      absolute dosimetry.
AB  - The measurement of absorbed dose to water in a solid-phantom may require a
      conversion factor because it may not be radiologically equivalent to water. One
      phantom developed for the use of dosimetry is a solid water, RW3 white
      polystyrene material by IBA. This has a lower mass-energy absorption coefficient
      than water due to high bremsstrahlung yield, which affects the accuracy of
      absolute dosimetry measurements. In this paper, we demonstrate the calculation of
      mass-energy absorption coefficient ratios, relative to water, from measurements
      in plastic water and RW3 with an Elekta Synergy linear accelerator (6 and 10 MV
      photon beams) as well as Monte Carlo modeling in BEAMnrc and DOSXYZnrc. From
      this, the solid-phantom-to-water correction factor was determined for plastic
      water and RW3.

PMID- 21960411
TI  - Reproducibility of functional MRI localization within the human somatosensory
      cortex.
AB  - PURPOSE: To evaluate the effect of fMRI localization approaches and region size
      on the reproducibility of digit localization in the human somatosensory cortex.
      MATERIALS AND METHODS: Vibrotactile stimulation was applied to digits 2 and 4
      producing cortical activation sites relating to each digit. Thirteen subjects
      were scanned twice on separate occasions in a 3 Tesla scanner using a voxel size
      of 2 mm. Regions of activity were thresholded to different sizes varying from 50
      to 1000 voxels. Three measures of position were acquired from these regions:
      center of gravity (COG), center co-ordinate and peak voxel. To account for
      registration errors, Euclidean distance between the two digits was computed.
      Reproducibility was determined in terms of the 95% confidence interval for
      individual position in X, Y, and Z and also the distance between the two digit
      locations. RESULTS: Region size of 200 most significant voxels was shown to have
      the best reproducibility. Center co-ordinate proved to be the most precise form
      of localizing activity with a 95% CI of 2.1 mm, 2.6 mm, and 3.1 mm in the X, Y,
      and Z axes. Euclidean distance between the center co-ordinates of the two digit
      activation sites was shown to be a reliable means of overcoming registration
      errors with a 95% CI of 1.7 mm. CONCLUSION: This study shows a high level of
      reproducibility for fMRI localization in the somatosensory system.

PMID- 21960412
TI  - Pelvic reconstruction after abdominoperineal resection: a pilot study using an
      absorbable synthetic prosthesis.
AB  - BACKGROUND: Abdominoperineal resection (APR) is not free of complications, in
      particular complications due to the occupation of the pelvis by the small bowel
      after surgery. A number of surgical techniques have been described to prevent the
      small bowel from entering and adhering to the pelvis (pelvic partition), but
      there is no agreement concerning their use. The aim of this study was to evaluate
      the feasibility, effectiveness and safety of using an absorbable synthetic
      prosthetic material for pelvic partitioning after APR. METHODS: A prospective non
      randomised longitudinal pilot study was carried out on a series of 10 patients
      who underwent APR due to lower-third rectal cancer, in order to evaluate the
      feasibility, safety and efficacy of pelvic partitioning with an absorbable
      synthetic prosthetic material. RESULTS: In all the patients, it was possible to
      perform a radical resection and to install the prosthesis. After a mean follow-up
      of 9 months (range: 4-18 months), no abdominal or perineal complications were
      detected. One patient (10%) suffered chronic pelvic pain. CONCLUSIONS: Pelvic
      partition after APR of the rectum with an absorbable synthetic prosthesis is
      feasible, effective and safe.

PMID- 21960413
TI  - Complement in cancer and cancer immunotherapy.
AB  - Recently, there has been an increase of interest in the use of biological or
      immune-based therapies for patients with malignancies. This has been informed by
      the deeper understanding of the crosstalk between the host immune system and
      malignant tumours, as well as the potential advantages of immunotherapy-high
      specificity and less toxicity compared to standard approaches. The particular
      emphasis of this article is on the role of the complement system in tumour growth
      and antibody-based cancer immunotherapy. The functional consequences from
      overexpression of complement regulators by tumours and the development of
      strategies for overcoming this are discussed in detail. This review discusses
      these issues with a view to inspiring the development of new agents that could be
      useful for the treatment of cancer.

PMID- 21960414
TI  - Ovarian cancer risk factors by histologic subtypes in the NIH-AARP Diet and
      Health Study.
AB  - Data suggest that risk factors for ovarian carcinoma vary by histologic type, but
      findings are inconsistent. We prospectively evaluated risk factors by
      histological subtypes of incident ovarian cancer (n = 849) in a cohort of 169,391
      women in the NIH-AARP Diet and Health Study. We constructed Cox models of
      individual exposures by comparing case subtypes to the entire non-case group and
      assessed p-heterogeneity in case-case comparisons using serous as the reference
      category. Substantial risk differences between histologic subtypes were observed
      for menopausal hormone therapy (MHT) use, oral contraceptive (OC) use, parity and
      body mass index (p-heterogeneity = 0.01, 0.03, 0.05, 0.03, respectively). MHT
      users were at increased risk for all histologic subtypes except for mucinous
      carcinomas, where risk was reduced (relative risk (RR) = 0.37; 95% confidence
      interval (CI): 0.18, 0.80). OC users were only at significantly decreased risk
      for serous cancers (RR = 0.69; 95% CI: 0.55, 0.85). Although parity was inversely
      associated with risk of all subtypes, the RRs ranged from 0.28 (clear cell) to
      0.83 (serous). Obesity was a significant risk factor only for endometrioid
      cancers (RR = 1.64; 95% CI: 1.00, 2.70). Our findings support a link between
      etiological factors and histological heterogeneity in ovarian carcinoma.

PMID- 21960415
TI  - Genetic structure and core collection of the World Olive Germplasm Bank of
      Marrakech: towards the optimised management and use of Mediterranean olive
      genetic resources.
AB  - The conservation of cultivated plants in ex-situ collections is essential for the
      optimal management and use of their genetic resources. For the olive tree, two
      world germplasm banks (OWGB) are presently established, in Cordoba (Spain) and
      Marrakech (Morocco). This latter was recently founded and includes 561 accessions
      from 14 Mediterranean countries. Using 12 nuclear microsatellites (SSRs) and
      three chloroplast DNA markers, this collection was characterised to examine the
      structure of the genetic diversity and propose a set of olive accessions
      encompassing the whole Mediterranean allelic diversity range. We identified 505
      SSR profiles based on a total of 210 alleles. Based on these markers, the genetic
      diversity was similar to that of cultivars and wild olives which were previously
      characterised in another study indicating that OWGB Marrakech is representative
      of Mediterranean olive germplasm. Using a model-based Bayesian clustering method
      and principal components analysis, this OWGB was structured into three main gene
      pools corresponding to eastern, central and western parts of the Mediterranean
      Basin. We proposed 10 cores of 67 accessions capturing all detected alleles and
      10 cores of 58 accessions capturing the 186 alleles observed more than once. In
      each of the 10 cores, a set of 40 accessions was identical, whereas the remaining
      accessions were different, indicating the need to include complementary criteria
      such as phenotypic adaptive and agronomic traits. Our study generated a molecular
      database for the entire OWGB Marrakech that may be used to optimise a strategy
      for the management of olive genetic resources and their use for subsequent
      genetic and genomic olive breeding.

PMID- 21960416
TI  - Renal sympathetic denervation for treatment of electrical storm: first-in-man
      experience.
AB  - INTRODUCTION: Sympathetic activity plays an important role in the pathogenesis of
      ventricular tachyarrhythmia. Catheter-based renal sympathetic denervation (RDN)
      is a novel treatment option for patients with resistant hypertension, proved to
      reduce local and whole-body sympathetic activity. METHODS: Two patients with
      chronic heart failure (CHF) (non-obstructive hypertrophic and dilated
      cardiomyopathy, NYHA III) suffering from therapy resistant electrical storm
      underwent therapeutic renal denervation. In both patients, RDN was conducted with
      agreement of the local ethics committee and after obtaining informed consent.
      RESULTS: The patient with hypertrophic cardiomyopathy had recurrent monomorphic
      ventricular tachycardia despite extensive antiarrhythmic therapy, following
      repeated endocardial and epicardial electrophysiological ablation attempts to
      destroy an arrhythmogenic intramural focus in the left ventricle. The second
      patient, with dilated nonischemic cardiomyopathy, suffered from recurrent
      episodes of polymorphic ventricular tachycardia and ventricular fibrillation. The
      patient declined catheter ablation of these tachycardias. In both patients, RDN
      was performed without procedure-related complications. Following RDN, ventricular
      tachyarrhythmias were significantly reduced in both patients. Blood pressure and
      clinical status remained stable during the procedure and follow-up in these
      patients with CHF. CONCLUSION: Our findings suggest that RDN is feasible even in
      cardiac unstable patients. Randomized controlled trials are urgently needed to
      study the effects of RD in patients with electrical storm and CHF.

PMID- 21960417
TI  - N-terminal pro-B-type natriuretic peptide in the circulation of fetuses with
      cardiac malformations.
AB  - Cardiac malformations with impact on loading patterns have the potential to
      progress to irreversible loss of ventricular function during human fetal life. N
      terminal pro-B-type natriuretic peptide (nt-proBNP) is a marker of cardiac
      dysfunction and involved in cardiac remodeling and fibrosis. We evaluated nt
      proBNP levels in the circulation of human fetuses with cardiac defects. A total
      of 45 cases and 75 controls during the second half of gestation were recruited.
      Nt-proBNP concentrations were determined in venous specimens obtained by fetal
      blood sampling. Results were correlated to echocardiography and Doppler studies.
      Mean gestational age was 26.9 weeks (range 21.0-33.4 weeks). Levels of
      circulating nt-proBNP were elevated in fetuses with cardiac defects (mean 6,896
      ng/L (range 595-42,479 ng/L) vs. 1,867 ng/L (73-3,751 ng/L), p < 0.001). In the
      presence of abnormal Doppler indices a further increase was detected (mean 11,287
      ng/L (range 1,403-42,479 ng/L) vs. 4,659 ng/L (595-30,848 ng/L), p = 0.021). No
      difference was found in fetuses with co-existing growth restriction.
      Malformations were classified according to their hemodynamic effect. Compared to
      shunt defects nt-proBNP concentrations were significantly higher in left or right
      ventricular outflow tract obstruction with intact ventricular septum (mean 15,639
      ng/L (range 2,301-42,479 ng/L) vs. 3,891 ng/L (595-13,752 ng/L), p = 0.013), and
      corresponded to the degree of ventricular dysfunction. In the circulation of
      human fetuses with cardiac defects levels of circulating nt-proBNP are elevated.
      Concentrations correlate with the type of myocardial wall stress. This finding
      supports a role for nt-proBNP as early indicator of intrauterine cardiovascular
      dysfunction and cardiac remodeling.

PMID- 21960418
TI  - Prognostic utility of T-wave alternans in a real-world population of patients
      with left ventricular dysfunction: the PREVENT-SCD study.
AB  - BACKGROUND: The predictive value of T-wave alternans (TWA) for lethal ventricular
      tachyarrhythmia in patients with left ventricular (LV) dysfunction is
      controversial. Also, long-term arrhythmia risk of patients ineligible for the TWA
      test is unknown. METHODS: This was a multicenter, prospective observational study
      of patients with LV ejection fraction <=40% due to ischemic or non-ischemic
      cardiomyopathies, designed to evaluate the prognostic value of TWA for lethal
      ventricular tachyarrhythmia. The primary end point was a composite of sudden
      cardiac death, sustained rapid ventricular tachycardia (VT) or ventricular
      fibrillation (VF), and appropriate defibrillator therapy for rapid VT or VF.
      RESULTS: Among 453 patients enrolled in the study, 280 (62%) were eligible for
      the TWA test. TWA was negative in 82 patients (29%), who accounted for 18% of the
      total population. The median of follow-up was 36 months. The 3-year event-free
      rate for the primary end point was significantly higher in TWA-negative patients
      (97.0%) than in TWA non-negative patients (89.5%, P = 0.037) and those ineligible
      for the TWA test (84.4%, P = 0.003). Multivariable analysis identified both non
      negative TWA [hazard ratio (HR) 4.43; 95% confidence interval (CI) 1.02-19.2; P =
      0.047) and ineligibility for the TWA test (HR 6.89; 95% CI 1.59-29.9; P = 0.010)
      to be independent predictors of the primary end point. CONCLUSIONS: TWA showed
      high negative predictive ability for lethal ventricular tachyarrhythmia in
      patients with LV dysfunction, although the TWA-negative patients accounted for
      only 18% of the entire population. Those ineligible for the TWA test had the
      highest risk for lethal ventricular tachyarrhythmia.

PMID- 21960419
TI  - Hotline update of clinical trials and registries presented at the at the European
      Society of Cardiology Congress in Paris 2011.
AB  - This article provides information and commentaries on trials which were presented
      at the Hotline and Clinical Trial Update Sessions during the Late Breaking
      Clinical Trial Sessions European Society of Cardiology Congress, held in Paris,
      France, from 27th to 31st August 2011. This article gives an overview on a number
      of novel clinical trials in the field of cardiovascular medicine, which were
      presented. The data have been presented by leading experts in the accordant field
      with relevant positions in the trials. Unpublished reports should be considered
      as preliminary data as the analysis may change in the final publications. The
      comprehensive summaries have been generated from the oral presentation and the
      webcasts of the European Society of Cardiology, similar as previously reported
      (Lenski et al. in Clin Res Cardiol Off J Ger Card Soc 99: 679-692, 2010) and
      should provide the readers with the most comprehensive information of relevant
      publications. The data were presented by leading experts in the field with
      relevant positions in the trials.

PMID- 21960420
TI  - Cardioprotective efficacy of a novel antioxidant mix VitaePro against ex vivo
      myocardial ischemia-reperfusion injury.
AB  - Circumstantial evidence frequently implicates oxygen-derived free radicals and
      oxidative stress as mediators of myocardial ischemia/reperfusion (I/R) injury.
      Therefore, external supplementation of natural antioxidants plays a main role as
      cardioprotective compounds. This study was designed to evaluate the
      cardioprotective effect of VitaePro (70 mg/kg body weight, 21 days), a novel
      antioxidant mix of astaxanthin, lutein and zeaxanthin in a rat ex vivo model of
      ischemia/reperfusion injury. The cardioprotective effect of VitaePro was also
      compared with vitamin E (70 mg/kg body weight, 21 days) treatment. Rats were
      randomized into control I/R (CIR), VitaePro I/R (VPIR) and Vitamin E I/R (VEIR).
      After 21 days of oral treatment, isolated hearts from each group were subjected
      to 30 min of ischemia followed by 2 h of reperfusion. In the VPIR group compared
      to CIR and VEIR groups at 2 h of reperfusion, increased left ventricular
      functional recovery, such as left ventricular developed pressure (92.7 +/- 0.7
      vs. 85.3 +/- 0.3 and 89.4 +/- 1.2 mm Hg), dp/dt max (2518.7 +/- 77.9 vs. 1962.5
      +/- 24 and 2255.7 +/- 126.6 mm Hg/s), and aortic flow (21.5 +/- 1.36 vs. 4.4 +/-
      0.6 and 13.2 +/- 1.02 ml/min) were observed. The infarct size (27.68 +/- 1.7 vs.
      45.4 +/- 1.8 and 35.4 +/- 0.6%), apoptotic cardiomyocytes (61.7 +/- 10.6 vs.
      194.1 +/- 14.8 and 118.7 +/- 15.4 counts/100 HPF) and thiobarbituric acid
      reactive substances levels (80 +/- 3 vs. 127 +/- 5 and 103 +/- 2 nM/mg tissue)
      also were decreased in VPIR group when compared to CIR and VEIR. As evidenced by
      the data, administration of vitamin E offered substantial cardioprotection to I/R
      injury, but VitaePro enhanced cardioprotection significantly more than vitamin E
      treatment. Taken in concert, the results of this study suggests that the oral
      ingestion of VitaePro protects myocardium from ischemia/reperfusion injury by
      decreasing oxidative stress and apoptosis, which may be of therapeutic benefit in
      the treatment of cardiovascular complications. However, further in vivo animal
      and human intervention studies are warranted before establishing any
      recommendations about usage of VitaePro for human cardiovascular complications. 

PMID- 21960421
TI  - Meridian is a three-dimensional network from bio-electromagnetic radiation
      interference: an interference hypothesis of meridian.
AB  - An electromagnetic radiation field within a biological organism is characterized
      by non-local interference. The interfering beams form a unitary tridimensional
      network with beams of varying intensity, also called striae, which are
      distributed on the organism surface. These striae are equivalent to semi
      reflectors. The striae carry bio-information of corresponding organs and, thus,
      integrate all tissues, and organs of the organism. The longitudinal striae are
      classified as channels, while the transverse striae are collaterals. The
      acupoints are seen as the points where electromagnetic interfering striae
      intersect or converge. This hypothesis builds a foundation to understand the
      traditional Chinese medicine, including acupuncture, from the perspective of
      scientific knowledge.

PMID- 21960422
TI  - Semisynthesis of prenylated Rab GTPases by click ligation.

PMID- 21960423
TI  - Thoracic wall reconstruction for primary malignancies in children: short- and
      long-term results.
AB  - AIM: Primary thoracic wall malignancy is a rare and diverse entity in children.
      Surgical treatment commonly involves major chest wall resection causing large
      defects requiring complex reconstruction. In adults, the use of alloplastic
      and/or xenogenic materials and muscle flap repair is well established. However,
      literature provides only little information on procedures in children. We report
      our experience in 8 consecutive children who underwent chest wall resection and
      reconstruction with regard to surgical treatment and outcome. PATIENTS AND
      METHODS: Retrospective study of all children with primary malignant chest wall
      tumors requiring rib resection and reconstruction with prosthetic material
      performed in our institution between November 2002 and April 2010. Endpoints were
      postoperative complications and long-term results, focusing on scoliosis defined
      radiologically by the Cobb angle. RESULTS: 8 children (7 male, 1 female) with a
      median age of 10.6 (4.1-18.9) years underwent resection of thoracic wall tumors.
      A mean number of 3 (1-5) ribs were resected. Stability was obtained using rigid
      prosthetic material (STRATOSTM titanium bar) in 2 patients and/or non-rigid
      prosthetic material (Goretex(r) patch in 6 patients, Vicryl(r) patch in 3
      patients, Tutopatch(r) in 1 patient). A muscular flap was added in 5 patients.
      Postoperative complications included superficial wound infection (n = 2) and
      dislocation of a titanium bar necessitating removal in 1 patient. No infections
      of the prosthetic material were observed. No perioperative mortality occurred. At
      a mean follow-up of 37.5 (4-97) months, 6 patients were alive. 2 patients died
      due to early tumor recurrence. Mild scoliosis (Cobb angle 10-20 degrees ) was
      detected in 2 of the surviving patients (33%). CONCLUSION: Surgical
      reconstruction after resection of malignant thoracic wall tumors using non-rigid
      prosthetic material is safe and effective in pediatric patients, whereas rigid
      prosthetic material might dislocate. Scoliosis represents a long-term
      complication after chest wall reconstruction and should be monitored during
      routine follow-up.

PMID- 21960424
TI  - Gastric outlet obstruction caused by heterotopic pancreatitis.

PMID- 21960425
TI  - Evaluation of nitric oxide (NO) and nitric oxide synthases (NOS) in the amniotic
      fluid in an experimental gastroschisis rat model.
AB  - Intestinal damage due to gastroschisis (G), an anomaly found with increasing
      incidence by pediatric surgeons, is intimately associated with endogenous nitric
      oxide (NO) production and NO synthase (NOS) expression. AIM: Aim of the study was
      to evaluate NO production and NOS isoforms in the intestine and amniotic fluid
      (AF) using a rat model of gastroschisis. METHODS: A gastroschisis rat model was
      surgically created at 18.5 days of gestation (term=22 days). 3 groups of 12
      fetuses each were studied: control (C), sham (S) and (G). Morphometric data of
      body weight (BW), intestinal weight (IW) and the IW/BW ratio were evaluated and
      compared. Indirect quantification of NO (nitrite and nitrate - NOx) was analyzed
      by chemiluminescence, and the expression of the 3 isoforms was analyzed by
      Western blotting. RESULTS: Group G showed an increase in IW and IW/BW compared
      with groups C and S. IW: G=0.27 +/- 0.06, C=0.20 +/- 0.02, S=0.20 +/- 0.02
      (p<0.01); IW/BW: G=4.11 +/- 0.57, C=5.21 +/- 1.04, S=5.18 +/- 1.23 (p<0.05). NO
      in the G group was lower in the intestine and higher in AF, as opposed to C and
      S, where it had increased in the intestine and decreased in AF. Intestinal NOx:
      G=0.85 +/- 0.28, C=1.86 +/- 0.82, S=1.80 +/- 0.69 (p<0.05); NOx in AF: G=161.87
      +/- 52.11, C=6.99 +/- 5.45, S=48.73 +/- 13.183 (p<0.001). CONCLUSION: The
      intestinal inflammation in gastroschisis promotes the release of nitric oxide to
      the environment (AF). Perhaps NO in the AF may be an inflammatory marker for G.

PMID- 21960426
TI  - A novel HLXB9 mutation in a Chinese family with Currarino syndrome.

PMID- 21960427
TI  - Our experience with single lung ventilation in thoracoscopic paediatric surgery.
AB  - INTRODUCTION: Data on the feasibility and effects of single lung ventilation
      (SLV) in children are scarce. We conducted a retrospective study on the
      feasibility of SLV during video-assisted thoracoscopic surgery (VATS) in children
      and adolescents undergoing major thoracic procedures. METHODS: A retrospective
      chart review of all records from patients who underwent VATS at our institution
      from 2000 to 2010 was done. Patients receiving SLV were analysed in detail.
      Endpoints of the analysis were conversion to open thoracotomy (frequency and
      reasons), postoperative duration of ventilation, and pulmonary complications such
      as radiologically confirmed atelectasis and pneumonia. RESULTS: 74 out of 305
      patients (24%, 43 boys, 31 girls) with a mean age of 9.4 years (56 days-18 years)
      and mean weight of 34 kg (4.5-76 kg) had SLV. Lung resection was done in 43
      (58%), pleural surgery in 17 (23%), a combination of both in 7 (9%), and
      mediastinal procedures in 7 (9%). 11 patients (15%) required conversion of VATS
      to open surgery, mostly because of problems with exposure of the operative field
      (73%). 32 patients (43%) were extubated immediately after the operation, whereas
      8 (11%) required ventilation for more than 24 h. The mean intensive care unit
      stay was 1.6 days. 18 patients (24%) developed radiologically confirmed
      atelectasis, and 1 patient (1%) required bronchoscopic clearance. Pneumonia
      occurred in 1 case (1%) and was successfully treated with antibiotics.
      CONCLUSION: SLV is feasible in children and adolescents undergoing VATS for a
      broad spectrum of procedures. However, despite SLV, the conversion rate in our
      series was 15%. The main reason for conversion was problems with exposure of the
      operative field. The complication rate for SLV was low. Atelectasis developed in
      every fourth patient but usually resolved spontaneously, and intervention to
      achieve ventilation was rarely indicated.

PMID- 21960428
TI  - Core temperature falls during laparotomy in infants with necrotizing
      enterocolitis.
AB  - AIM OF THE STUDY: Intraoperative hypothermia may have a detrimental clinical
      effect. Preterm infants undergoing laparotomy for necrotizing enterocolitis (NEC)
      are particularly at risk. We investigated the relationship between intraoperative
      temperature and morbidity and outcome in infants with NEC. METHODS: A review of
      all laparotomies for NEC (n = 82, 69 infants) performed between Jan 2008 and Jan
      2011 in our institution was done. Relationships between intraoperative
      temperature and intra- and postoperative fluid and blood product requirements,
      postoperative clinical status (sequential organ failure assessment [SOFA] score)
      and outcome were determined. Data (mean [range]) were compared using paired t
      test and regression analysis. RESULTS: Data were available for 52 laparotomies
      (49 infants). The lowest intraoperative core temperature was significantly lower
      than the preoperative temperature (peri-op 34.9  degrees C [31.5-37.0] vs. pre-op
      37.0  degrees C [35.8-38.0]; p < 0.0001). There was a statistically significant
      inverse relationship between mean intraoperative temperature and intraoperative
      blood transfusion requirement (p = 0.01). There were no statistically significant
      relationships between intraoperative temperature and other blood product or
      volume requirements, postoperative infective complications, change in SOFA score
      following surgery, length of stay, or mortality. CONCLUSIONS: During laparotomy
      for NEC, there is a significant and profound drop in core temperature. The effect
      of this on short-term morbidity and long-term outcome (e.g., neurodevelopment)
      warrants further investigation.

PMID- 21960429
TI  - The right-sided aortic arch in children with oesophageal atresia and tracheo
      oesophageal fistula.
AB  - AIM: A right-sided aortic arch (RAA) occurs in around 5% of patients with
      oesophageal atresia and tracheo-oesophageal fistula (OA/TOF). This anatomical
      variation can complicate the operative management of these patients, as it is
      often not diagnosed preoperatively but only discovered at thoracotomy, and it
      remains unproven as to whether a right or left thoracotomy is the best operative
      approach. This retrospective study aimed to determine the prevalence of RAA in
      OA/TOF, review the accuracy of preoperative investigations, and investigate the
      best operative approach, by reviewing the literature and our own patient series.
      METHODS: The case notes of all infants with OA/TOF over a 15 year period (1994
      2008) were retrospectively analysed to identify those with a RAA. Birth weight,
      gestational age, associated anomalies, preoperative investigations, surgical
      management, postoperative complications and long-term prognosis were all
      extracted. MAIN RESULTS: A total of 107 case notes of OA/TOF infants were
      reviewed, identifying 4 with a RAA. Preoperative echocardiography was performed
      in all of the 4 RAA infants, but RAA was only identified in one. All 4 infants
      were managed surgically via a right thoracotomy, regardless of the
      echocardiography result, with primary anastomosis achieved successfully in all. A
      laryngeal cleft repair was performed in 1 infant due to an interarytenoid cleft.
      Laparoscopic fundoplication was performed in 1 patient, because of severe gastro
      oesophageal reflux. There were no postoperative anastomotic leaks, bleeding, or
      deaths in this group. CONCLUSION: In our study, the incidence of RAA in OA/TOF
      was 3.7%. Preoperative echocardiography identified the RAA in only 1 of 4 cases.
      However, echocardiography was helpful for diagnosing other cardiac anomalies,
      which might have potentially affected the management of these patients. Previous
      studies have cited the operative difficulties associated with RAA and OA/TOF.
      However, in this series of 4 infants, primary anastomosis was achieved via
      conventional right thoracotomy without complication, and with no effect on
      outcome or prognosis. Therefore, we conclude that, where possible, a conventional
      right-sided thoracotomy should be performed in OA/TOF patients with a RAA.

PMID- 21960430
TI  - Oxygen versus sulfur: Structure and reactivity of substituted arsine oxides and
      arsine sulfides.
AB  - Although arsenic in its inorganic forms is a well know toxic agent,
      biotransformations in the environment and in the human body can produce
      organoarsenic compounds that are generally of much lower toxicity. Foremost among
      these products is a range of dimethylated arsine oxides and their analogous
      sulfides, which are crucial to the arsenic detoxification process. We have
      investigated the formation and interconversion of substituted and unsubstituted
      arsenicals (R22As(=Z)R1, R2 = CH3, R1 = CH2CH2OH, CH2COOH; Z = S or O) with
      density functional theory (DFT)/B3LYP. Formation of isomers including a cyclic
      hydrogen bonded conformer is observed for the ethanol and acetate derivatives.
      Furthermore, investigating the reaction of arsine oxide with hydrogen sulfide
      revealed the formation of arsine sulfide via pentacoordinated trigonal
      bipyramidal intermediates. A tetragonal pyramidal transition state was located
      enabling exchange of equatorial and axial positions in the trigonal bipyramidal
      species. The reaction was proven exothermic for all studied substituents
      (DeltaE(rxn) -50 to -80 kJ/mol). This fundamental study shows that H2S easily
      leads to the formation of thio-organoarsenicals. Conversion of arsine sulfides
      into their corresponding arsine oxides is experimentally accomplished with
      hydrogen peroxide, which could also be rationalized by means of ab initio
      calculations showing high exothermicity (DeltaE(rxn) ca. -550 kJ/mol). Reactions
      are considered at different levels of theory (i.e., DFT, second and fourth order
      Moller-Plesset (MP) perturbation theory) including two solvation models for DFT,
      which show good agreement for resulting geometries and reaction energies. Hence,
      the widely used B3LYP/6-31G** combination is a suitable method for the
      description of molecular organoarsenicals.

PMID- 21960431
TI  - Conjugated macrocycles: concepts and applications.
AB  - One of the most important objectives in materials, chemical, and physical
      sciences is the creation of large conjugated macrocycles with well-defined
      shapes, since such molecules are not only theoretically and experimentally
      interesting but also have potential applications in nanotechnology. Fully
      unsaturated macrocycles are regarded as models for infinitely conjugated pi
      systems with inner cavities, and exhibit unusual optical and magnetic behavior.
      Macrocycles have interior and exterior sites, and site-specific substitution at
      both or either site can afford attractive structures, such as 1D, 2D, and 3D
      supramolecular nanostructures. These nanostructures could be controlled through
      the use of pi-extended large macrocycles by a bottom-up strategy. Numerous shape
      persistent pi-conjugated macrocycles have been synthesized, but only a few are on
      the nanoscale. This Review focuses on nanosized pi-conjugated macrocycles (>1 nm
      diameter) and giant macrocycles (>2 nm diameter), and summarizes their syntheses
      and properties.

PMID- 21960432
TI  - Selection of a phylogenetically informative region of the norovirus genome for
      outbreak linkage.
AB  - The recognition of a common source norovirus outbreak is supported by finding
      identical norovirus sequences in patients. Norovirus sequencing has been
      established in many (national) public health laboratories and academic centers,
      but often partial and different genome sequences are used. Therefore, agreement
      on a target sequence of sufficient diversity to resolve links between outbreaks
      is crucial. Although harmonization of laboratory methods is one of the keystone
      activities of networks that have the aim to identify common source norovirus
      outbreaks, this has proven difficult to accomplish, particularly in the
      international context. Here, we aimed at providing a method enabling
      identification of the genomic region informative of a common source norovirus
      outbreak by bio-informatic tools. The data set of 502 unique full length capsid
      gene sequences available from the public domain, combined with epidemiological
      data including linkage information was used to build over 3,000 maximum
      likelihood (ML) trees for different sequence lengths and regions. All ML trees
      were evaluated for robustness and specificity of clustering of known linked
      norovirus outbreaks against the background diversity of strains. Great
      differences were seen in the robustness of commonly used PCR targets for cluster
      detection. The capsid gene region spanning nucleotides 900-1,400 was identified
      as the region optimally substituting for the full length capsid region.
      Reliability of this approach depends on the quality of the background data set,
      and we recommend periodic reassessment of this growing data set. The approach may
      be applicable to multiple sequence-based data sets of other pathogens.

PMID- 21960433
TI  - In vitro characterization of EHV-4 gG-deleted mutant.
AB  - Equine herpesvirus 4 (EHV-4) is an important pathogen that causes respiratory
      tract disease in horse populations worldwide. Glycoprotein G (gG) homologs have
      been identified in several alphaherpesviruses as minor non-essential membrane
      anchored glycoproteins. In this study, EHV-4 gG deletion mutant has been
      generated by using bacterial artificial chromosome technology to investigate the
      role of gG in viral pathogenesis. Our findings reported here revealed no
      significant difference between parental EHV-4 and gG-negative strain in their
      replication cycle in cell culture. Furthermore, virus titers and plaque formation
      were comparable in both viruses. It is noteworthy that these findings disagree
      with the previously published study describing gG deletion in another EHV-4
      strain.

PMID- 21960434
TI  - Virulent Newcastle disease virus in Nigeria: identification of a new clade of sub
      lineage 5f from livebird markets.
AB  - Newcastle disease (ND), caused by Avian Paramyxovirus Type 1, is a highly
      contagious and devastating viral disease of poultry of worldwide distribution
      with an enormous economic impact. Although ND is reported to be endemic in
      Nigeria, little information exists on the molecular epidemiology and the lineage
      distribution of the Newcastle disease viruses (NDVs) in the country, especially
      in the live bird markets (LBMs). Recent studies reported the identification of
      three unique sub-lineages. namely; 5f, 5g and 5h in West Africa, and sub-lineages
      5f and 5g in particular in non-commercial farms in Nigeria. In this study, 33 NDV
      isolates, which included NDVs recovered from LBMs in Nigeria, during active
      surveillance from 2007 to 2008 and viruses recovered from outbreaks in backyard
      and commercial chicken farms within the same period were analysed. Based on
      determination of the F(0) cleavage site amino acid sequence and phylogenetic
      analysis, the isolates were classified as virulent; 16 strains were identified as
      sub-lineage 5g and 17 as sub-lineage 5f. Interestingly, 13 strains from the 5f
      group formed a distinct cluster that was not identified by other groups in
      similar studies. The close genetic similarities identified, provided evidence for
      the first time of the epidemiological link between the viruses circulating in the
      LBMs and those recovered from outbreaks in backyard and commercial chicken farms
      in Nigeria between 2007 and 2008. The emergence and identification of new sub
      lineages provide an insight into the high rate of genetic drift occurring in NDV
      strains in Nigeria, and raises a lot of concerns about the efficacy of current ND
      control measures in the country.

PMID- 21960435
TI  - Infestation of Japanese native honey bees by tracheal mite and virus from non
      native European honey bees in Japan.
AB  - Invasion of alien species has been shown to cause detrimental effects on habitats
      of native species. Insect pollinators represent such examples; the introduction
      of commercial bumble bee species for crop pollination has resulted in competition
      for an ecological niche with native species, genetic disturbance caused by mating
      with native species, and pathogen spillover to native species. The European honey
      bee, Apis mellifera, was first introduced into Japan for apiculture in 1877, and
      queen bees have been imported from several countries for many years. However, its
      effects on Japanese native honey bee, Apis cerana japonica, have never been
      addressed. We thus conducted the survey of honey bee viruses and Acarapis mites
      using both A. mellifera and A. c. japonica colonies to examine their infestation
      in native and non-native honey bee species in Japan. Honey bee viruses, Deformed
      wing virus (DWV), Black queen cell virus (BQCV), Israeli acute paralysis virus
      (IAPV), and Sacbrood virus (SBV), were found in both A. mellifera and A. c.
      japonica colonies; however, the infection frequency of viruses in A. c. japonica
      was lower than that in A. mellifera colonies. Based on the phylogenies of DWV,
      BQCV, and SBV isolates from A. mellifera and A. c. japonica, DWV and BQCV may
      infect both honey bee species; meanwhile, SBV has a clear species barrier. For
      the first time in Japan, tracheal mite (Acarapis woodi) was specifically found in
      the dead honey bees from collapsing A. c. japonica colonies. This paper thus
      provides further evidence that tracheal-mite-infested honey bee colonies can die
      during cool winters with no other disease present. These results demonstrate the
      infestation of native honey bees by parasite and pathogens of non-native honey
      bees that are traded globally.

PMID- 21960436
TI  - A genome-wide screen identifies yeast genes required for protection against or
      enhanced cytotoxicity of the antimalarial drug quinine.
AB  - Quinine is used in the treatment of Plasmodium falciparum severe malaria.
      However, both the drug's mode of action and mechanisms of resistance are still
      poorly understood and subject to debate. In an effort to clarify these questions,
      we used the yeast Saccharomyces cerevisiae as a model for pharmacological studies
      with quinine. Following on a previous work that examined the yeast genomic
      expression program in response to quinine, we now explore a genome-wide screen
      for altered susceptibility to quinine using the EUROSCARF collection of yeast
      deletion strains. We identified 279 quinine-susceptible strains, among which 112
      conferred a hyper-susceptibility phenotype. The expression of these genes, mainly
      involved in carbohydrate metabolism, iron uptake and ion homeostasis functions,
      is required for quinine resistance in yeast. Sixty-two genes whose deletion leads
      to increased quinine resistance were also identified in this screen, including
      several genes encoding ribosome protein subunits. These well-known potential drug
      targets in Plasmodium are associated with quinine action for the first time in
      this study. The suggested involvement of phosphate signaling and transport in
      quinine tolerance was also studied, and activation of phosphate starvation
      responsive genes was observed under a mild-induced quinine stress. Finally, P.
      falciparum homology searches were performed for a selected group of 41 genes.
      Thirty-two encoded proteins possess homologs in the parasite, including subunits
      of a parasitic vacuolar H(+)-ATPase complex, ion and phosphate importers, and
      several ribosome protein subunits, suggesting that the results obtained in yeast
      are good candidates to be transposed and explored in a P. falciparum context.

PMID- 21960437
TI  - Metabolic changes in early childhood using LCModel with corrected water scaling
      method.
AB  - PURPOSE: To examine metabolic changes of the brain in early infancy measured by
      the LCModel with the water scaling method (LCModel-WS), and to determine whether
      the unsuppressed water signal (UWS) on the MR console and the area of the
      unsuppressed water peak (AUW) in the LCModel can be used to correct metabolite
      concentrations. MATERIALS AND METHODS: MR spectroscopy was performed on a 1.5
      Tesla MR scanner. To determine whether UWS and AUW increases linearly with PD and
      exp(-TE/T2), these values were measured using three phantoms with different PD
      and T2 values. UWS and AUW were also measured (PRESS, TR = 5000 ms, TE = 30 ms,
      VOI = 4.5 mL) in 57 pediatric controls (aged 2 weeks to 15 years). RESULTS:
      Phantom studies revealed UWS and AUW increases linearly with PD and exp(-TE/T2).
      UWS and AUW were high in controls younger than 2 years of age, but gradually
      decreased to become almost constant after 4 years (UWS = 504 * 10(3) , AUW = 2.05
      * 10(7)). AUW was linearly proportional to UWS in controls. These indicated that
      metabolite concentrations should be multiplied by the ratio of UWS/504 * 10(3) or
      AUW/2.05 * 10(7). Age dependent metabolite concentrations corrected by the ratio
      were obtained. CONCLUSION: Both UWS and AUW can be used to correct metabolite
      concentrations; these corrections can significantly improve quantification of
      metabolites' concentration in early childhood.

PMID- 21960439
TI  - Comment on the subsidence adjustment applied to the Kemp et al. proxy of North
      Carolina relative sea level.

PMID- 21960438
TI  - Impairments in life quality among clients in geriatric home care: associations
      with depressive and anxiety symptoms.
AB  - OBJECTIVE: The aim of this study was to determine the independent contributions
      of depressive and anxiety symptoms to quality of life among older adults who were
      receiving services through a home care program. METHODS: The study sample
      consisted of 66 community-dwelling older adults (ages 65 years and older), who
      were experiencing chronic medical illness and concomitant functional disability
      necessitating home care. Participants completed self-report measures of
      depression, anxiety, and health-related quality of life. Additional data on
      cognitive, health, and functional status were collected to be used as covariates.
      RESULTS: The associations of depressive symptoms with quality of life impairments
      in home care were substantial and pervasive. Depressive symptoms were
      significantly associated with quality of life impairments in nearly all domains.
      After controlling for depressive symptoms, anxiety symptoms accounted for
      additional and statistically significant variance in impaired life quality in the
      domains of mental health, role emotional functioning, and bodily pain.
      CONCLUSIONS: These results indicate that depressive and anxiety symptoms
      demonstrate negative associations with life quality among older adults in home
      care and highlight the importance of developing community-based programs to
      assess and treat depressive and anxiety symptoms among home care clients.

PMID- 21960440
TI  - Behavior-specific changes in transcriptional modules lead to distinct and
      predictable neurogenomic states.
AB  - Using brain transcriptomic profiles from 853 individual honey bees exhibiting 48
      distinct behavioral phenotypes in naturalistic contexts, we report that behavior
      specific neurogenomic states can be inferred from the coordinated action of
      transcription factors (TFs) and their predicted target genes. Unsupervised
      hierarchical clustering of these transcriptomic profiles showed three clusters
      that correspond to three ecologically important behavioral categories:
      aggression, maturation, and foraging. To explore the genetic influences
      potentially regulating these behavior-specific neurogenomic states, we
      reconstructed a brain transcriptional regulatory network (TRN) model. This brain
      TRN quantitatively predicts with high accuracy gene expression changes of more
      than 2,000 genes involved in behavior, even for behavioral phenotypes on which it
      was not trained, suggesting that there is a core set of TFs that regulates
      behavior-specific gene expression in the bee brain, and other TFs more specific
      to particular categories. TFs playing key roles in the TRN include well-known
      regulators of neural and behavioral plasticity, e.g., Creb, as well as TFs better
      known in other biological contexts, e.g., NF-kappaB (immunity). Our results
      reveal three insights concerning the relationship between genes and behavior.
      First, distinct behaviors are subserved by distinct neurogenomic states in the
      brain. Second, the neurogenomic states underlying different behaviors rely upon
      both shared and distinct transcriptional modules. Third, despite the complexity
      of the brain, simple linear relationships between TFs and their putative target
      genes are a surprisingly prominent feature of the networks underlying behavior.

PMID- 21960441
TI  - Mitochondrial antiviral signaling protein (MAVS) monitors commensal bacteria and
      induces an immune response that prevents experimental colitis.
AB  - RIG-I-like receptors (RLRs) activate host innate immune responses against virus
      infection through recruiting the mitochondrial adaptor protein MAVS (also known
      as IPS1, VISA, or CARDIF). Here we show that MAVS also plays a pivotal role in
      maintaining intestinal homeostasis. We found that MAVS knockout mice developed
      more severe mortality and morbidity than WT animals in an experimental model of
      colitis. Bone marrow transplantation experiments revealed that MAVS in cells of
      nonhematopoietic origin plays a dominant role in the protection against colitis.
      Importantly, RNA species derived from intestinal commensal bacteria activate the
      RIG-I-MAVS pathway to induce the production of multiple cytokines and
      antimicrobial peptides, including IFN-beta and RegIIIgamma. These results unveil
      a previously unexplored role of MAVS in monitoring intestinal commensal bacteria
      and maintaining tissue homeostasis.

PMID- 21960442
TI  - Regulation of tissue repair in plants.

PMID- 21960443
TI  - Mesenchymal stem cells impair in vivo T-cell priming by dendritic cells.
AB  - Dendritic cells (DC) are highly specialized antigen-presenting cells
      characterized by the ability to prime T-cell responses. Mesenchymal stem cells
      (MSC) are adult stromal progenitor cells displaying immunomodulatory activities
      including inhibition of DC maturation in vitro. However, the specific impact of
      MSC on DC functions, upon in vivo administration, has never been elucidated. Here
      we show that murine MSC impair Toll-like receptor-4 induced activation of DC
      resulting in the inhibition of cytokines secretion, down-regulation of molecules
      involved in the migration to the lymph nodes, antigen presentation to CD4(+) T
      cells, and cross-presentation to CD8(+) T cells. These effects are associated
      with the inhibition of phosphorylation of intracellular mitogen-activated protein
      kinases. Intravenous administration of MSC decreased the number of CCR7 and
      CD49dbeta1 expressing CFSE-labeled DC in the draining lymph nodes and hindered
      local antigen priming of DO11.10 ovalbumin-specific CD4(+) T cells. Upon labeling
      of DC with technetium-99m hexamethylpropylene amine oxime to follow their in vivo
      biodistribution, we demonstrated that intravenous injection of MSC blocks, almost
      instantaneously, the migration of subcutaneously administered ovalbumin-pulsed DC
      to the draining lymph nodes. These findings indicate that MSC significantly
      affect DC ability to prime T cells in vivo because of their inability to home to
      the draining lymph nodes and further confirm MSC potentiality as therapy for
      immune-mediated diseases.

PMID- 21960444
TI  - Motifs emerge from function in model gene regulatory networks.
AB  - Gene regulatory networks allow the control of gene expression patterns in living
      cells. The study of network topology has revealed that certain subgraphs of
      interactions or "motifs" appear at anomalously high frequencies. We ask here
      whether this phenomenon may emerge because of the functions carried out by these
      networks. Given a framework for describing regulatory interactions and dynamics,
      we consider in the space of all regulatory networks those that have prescribed
      functional capabilities. Markov Chain Monte Carlo sampling is then used to
      determine how these functional networks lead to specific motif statistics in the
      interactions. In the case where the regulatory networks are constrained to
      exhibit multistability, we find a high frequency of gene pairs that are mutually
      inhibitory and self-activating. In contrast, networks constrained to have
      periodic gene expression patterns (mimicking for instance the cell cycle) have a
      high frequency of bifan-like motifs involving four genes with at least one
      activating and one inhibitory interaction.

PMID- 21960445
TI  - Conformational trapping of mismatch recognition complex MSH2/MSH3 on repair
      resistant DNA loops.
AB  - Insertion and deletion of small heteroduplex loops are common mutations in DNA,
      but why some loops are prone to mutation and others are efficiently repaired is
      unknown. Here we report that the mismatch recognition complex, MSH2/MSH3,
      discriminates between a repair-competent and a repair-resistant loop by sensing
      the conformational dynamics of their junctions. MSH2/MSH3 binds, bends, and
      dissociates from repair-competent loops to signal downstream repair. Repair
      resistant Cytosine-Adenine-Guanine (CAG) loops adopt a unique DNA junction that
      traps nucleotide-bound MSH2/MSH3, and inhibits its dissociation from the DNA. We
      envision that junction dynamics is an active participant and a conformational
      regulator of repair signaling, and governs whether a loop is removed by MSH2/MSH3
      or escapes to become a precursor for mutation.

PMID- 21960446
TI  - Large area and structured epitaxial graphene produced by confinement controlled
      sublimation of silicon carbide.
AB  - After the pioneering investigations into graphene-based electronics at Georgia
      Tech, great strides have been made developing epitaxial graphene on silicon
      carbide (EG) as a new electronic material. EG has not only demonstrated its
      potential for large scale applications, it also has become an important material
      for fundamental two-dimensional electron gas physics. It was long known that
      graphene mono and multilayers grow on SiC crystals at high temperatures in
      ultrahigh vacuum. At these temperatures, silicon sublimes from the surface and
      the carbon rich surface layer transforms to graphene. However the quality of the
      graphene produced in ultrahigh vacuum is poor due to the high sublimation rates
      at relatively low temperatures. The Georgia Tech team developed growth methods
      involving encapsulating the SiC crystals in graphite enclosures, thereby
      sequestering the evaporated silicon and bringing growth process closer to
      equilibrium. In this confinement controlled sublimation (CCS) process, very high
      quality graphene is grown on both polar faces of the SiC crystals. Since 2003,
      over 50 publications used CCS grown graphene, where it is known as the "furnace
      grown" graphene. Graphene multilayers grown on the carbon-terminated face of SiC,
      using the CCS method, were shown to consist of decoupled high mobility graphene
      layers. The CCS method is now applied on structured silicon carbide surfaces to
      produce high mobility nano-patterned graphene structures thereby demonstrating
      that EG is a viable contender for next-generation electronics. Here we present
      for the first time the CCS method that outperforms other epitaxial graphene
      production methods.

PMID- 21960447
TI  - Function and survival after revision of hip resurfacing.
AB  - The purpose of this study was to compare functional outcome and survival of
      isolated acetabular, isolated femoral and both component revision after failure
      of primary Birmingham Hip Resurfacing. The Oswestry Outcome Centre prospectively
      collected data on 5000 hip resurfacing between 1997 and 2002. Of these, 182 hips
      were revised: 8% had revision of the acetabular component only, 42% had revision
      of the femoral component only to conventional stemmed prosthesis, and 50% had
      revision of both components to conventional total hip arthroplasty (THA). We used
      a postal questionnaire to assess function by Harris and Merle d'Aubigne and
      Postel hip scores and determined survival using re-revision as an endpoint. In
      patients with isolated acetabular revision, the median Harris hip score (HHS) was
      74 at a mean of 4.5 years follow up. Isolated femoral revision had a median HHS
      of 82 at a mean of 3.8 years. When both components were revised, the median HHS
      was 85 at a mean of 4 years. We observed no difference in HHS between the groups.
      There was an average survival of 92% at 10 years. Survival was significantly
      lower for isolated acetabular revision (75%) than isolated femoral (93%) or both
      component revision (96%).

PMID- 21960448
TI  - A biomechanical comparison of the thrust plate prosthesis and a stemmed
      prosthesis.
AB  - The thrust plate prosthesis (TPP) is a neck preserving femoral component in total
      hip arthroplasty (THA) which may facilitate more precise biomechanical
      reconstruction of the hip. The purpose of this study was to compare the
      biomechanical results of the TPP with a conventional THA. We compared
      anteroposterior radiographs from 60 patients who had undergone cementless THA,
      with 44 who had undergone a TPP. We measured the hip centre of rotation, femoral
      offset, limb length, and neck-shaft angle. The horizontal hip centre of rotation,
      vertical femoral offset, limb length and neck-shaft angle measurements showed a
      significant difference (p<0.05) in both groups when compared with preoperative
      values. However, the vertical hip centre of rotation and horizontal femoral
      offset measurements were different only in TPP patients when compared with
      preoperative values (p<0.05). When both groups (TPP and THA) were compared only
      the horizontal hip centre of rotation displayed a significant difference
      (p=0.003) in favor of the THA. Therefore, we found no difference in restoring the
      biomechanics of the hip using the two methods, and only the horizontal hip centre
      of rotation restoration favoured the THA. Our findings indicate that the TPP does
      not produce more accurate restoration of leg length or offset. Reproduction of
      hip mechanics after TPP may not be as good as has been suggested.

PMID- 21960449
TI  - Groin pain following hip resurfacing: a case-control study.
AB  - We compared 47 patients with groin pain following hip resurfacing to a matched
      control group. Functional scores and plain radiographs were assessed along with
      measurement of whole blood cobalt and chromium by inductively coupled mass
      spectrometry. Symptomatic patients underwent ultrasound scan of the affected hip.
      Mean functional outcomes were poor in those with pain and good in the control
      group. Groin pain was associated with valgus stem positioning and lower neck:head
      ratio (relatively narrow neck) (p=0.03, p=0.04 respectively). We classified
      patients with groin pain into two groups: biological and mechanical. The
      biological group had soft tissue abnormalities on USS and higher levels of cobalt
      and chromium (p=0.04, p=0.05 respectively). The mechanical group had normal USS,
      lower metal ion levels and more retroverted femoral components (p=0.01).

PMID- 21960450
TI  - Avascular necrosis of the femoral head after hip arthroscopy.
AB  - We report a case of a 61-year-old woman who underwent hip arthroscopy for a
      labral tear. The acetabular labrum was resected arthroscopically. Three months
      later, magnetic resonance imaging showed avascular necrosis of the femoral head.
      Theoretically, avascular necrosis following hip arthroscopy may result from
      traction on vessels supplying the femoral head, direct injury to such vessels
      during portal entrance, raised intra-articular pressure, prolonged operating time
      and damage to vessels during bony resection or osteochondroplasty for
      femoroacetabular impingement. We presume that avascular necrosis in our case was
      a result of a traction injury and increased intra-articular pressure.

PMID- 21960451
TI  - The prevalence of predisposing deformity in osteoarthritic hip joints.
AB  - It is becoming increasingly evident that hip joint deformities may be major
      contributors to the development of osteoarthritis, and the term 'idiopathic
      osteoarthritis' may be inappropriate in many cases. Our study cohort was derived
      from the Copenhagen Osteoarthritis Sub-study, a cross sectional population-based
      database of 4151 individuals, all of whom had a standard anteroposterior weight
      bearing pelvic radiograph taken. Hip joints were classified according to type and
      degree of deformity. We defined hip osteoarthritis by a minimum joint space width
      of < or = 2 mm. This cut-off has a significant relationship in both sexes with
      the clinical presentation. The study cohort which fulfilled these inclusion
      criteria consisted of 322 females (149 right hips and 173 left hips) and 162
      males (77 right hips and 85 left hips) with osteoarthritis. We found an overall
      prevalence of predisposing hip deformities in females of 62.4% and in males of
      78.9%. Minor and major deformities showed the same prevalence. Both sexes had a
      comparable prevalence of minor and major hip joint deformity, except for pistol
      grip deformity, which was more prevalent in men. We concluded that 'idiopathic
      osteoarthritis' is uncommon, and that even minor predisposing deformities are
      associated with hip osteoarthritis.

PMID- 21960452
TI  - Classic measures of hip dysplasia do not correlate with three-dimensional
      computer tomographic measures and indices.
AB  - Acetabular dysplasia is a precursor to osteoarthritis of the hip, and it causes
      acute and degenerative injuries of soft tissue stabilizers. Traditional
      radiographic assessments of dysplasia are useful in moderate and severe
      dysplasia, but they have questionable reliability in mild dysplasia. Computed
      tomography (CT) reconstruction provides a method for calculation of acetabular
      geometry and analysis of existing radiographic methods. We performed a
      retrospective radiographic review of anteroposterior pelvic films and their
      corresponding pelvic CT scans. Using 30 skeletally mature patients, we analyzed
      the following five measurements for 60 hips: lateral centre edge angle of Wiberg
      (LCE), Tonnis angle, Sharp angle, a modified Sharp angle, and the depth to width
      acetabular index. We also estimated hip surface areas, volumes, and ratios from 3
      D reconstructions of a CT scan taken within 60 days of the plain radiograph. The
      Pearson Correlation Coefficient was used to evaluate the relationship between the
      plain film measurements and the computed hip indices. No moderate or strong
      correlation was found between the measured plain film indices and the calculated
      hip indices. Traditional 2-D measurements used to define acetabular dysplasia
      have little to no ability to quantify hip volumes and surface areas. CT
      reconstruction provides a better screening tool in the identification of subtle
      acetabular hip dysplasia in adults. LEVEL OF EVIDENCE: Level III.

PMID- 21960453
TI  - Prevalence of human papillomavirus in women with invasive cervical carcinoma by
      HIV status in Kenya and South Africa.
AB  - Data on the prevalence of human papillomavirus (HPV) types in cervical carcinoma
      in women with HIV are scarce but are essential to elucidate the influence of
      immunity on the carcinogenicity of different HPV types, and the potential impact
      of prophylactic HPV vaccines in populations with high HIV prevalence. We
      conducted a multicentre case-case study in Kenya and South Africa. During 2007
      2009, frozen tissue biopsies from women with cervical carcinoma were tested for
      HPV DNA using GP5+/6+-PCR assay. One hundred and six HIV-positive (mean age 40.8
      years) and 129 HIV-negative women (mean age 45.7) with squamous cell carcinoma
      were included. Among HIV-positive women, the mean CD4 count was 334 cells/MUL and
      48.1% were on combined antiretroviral therapy. HIV-positive women had many more
      multiple HPV infections (21.6% of HPV-positive carcinomas) compared with HIV
      negative women (3.3%) (p < 0.001) and the proportion of multiple infections was
      inversely related to CD4 level. An excess of HPV18 of borderline statistical
      significance was found in HIV-positive compared with HIV-negative cases
      (Prevalence ratio (PR) = 1.9, 95% confidence interval (CI): 1.0-3.7, adjusted for
      study centre, age and multiplicity of infection). HPV16 and/or 18 prevalence
      combined, however, was similar in HIV-positive (66.7%) and HIV-negative cases
      (69.1%) (PR = 1.0, 95% CI: 0.9-1.2). No significant difference was found for
      other HPV types. Our data suggest that current prophylactic HPV vaccines against
      HPV16 and 18 may prevent similar proportions of cervical SCC in HIV-positive as
      in HIV-negative women provided that vaccine-related protection is sustained after
      HIV infection.

PMID- 21960454
TI  - Investigating Mithramycin deoxysugar biosynthesis: enzymatic total synthesis of
      TDP-D-olivose.
AB  - Mix'n'match: Enzymatic total synthesis of TDP-D-olivose was achieved, starting
      from TDP-4-keto-6-deoxy-D-glucose, by combining three pathway enzymes with one
      cofactor-regenerating enzyme. The results also revealed that MtmC is a
      bifunctional enzyme that can perform a 4-ketoreduction necessary for D-olivose
      biosynthesis besides the previously found C-methyltransfer for D-mycarose
      biosynthesis.

PMID- 21960455
TI  - Depression symptoms in boys with autism spectrum disorder and comparison samples.
AB  - This study compares severity of specific depression symptoms in boys with autism
      spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), or
      chronic multiple tic disorder (CMTD) and typically developing boys (Controls).
      Children were evaluated with parent and teacher versions of the Child Symptom
      Inventory-4 (CSI-4) and a demographic questionnaire. Mothers' and teachers'
      ratings generally indicated the most severe symptoms in boys with ASD +/- ADHD.
      Associations of depression with ASD severity and IQ varied considerably for
      specific symptoms of depression, ASD functional domain, and informant. Findings
      provide additional support for the differential influence of neurobehavioral
      syndromes on co-occurring symptom severity and illustrate how more fine-grained
      analyses of clinical phenotypes may contribute to a better understanding of
      etiology and current nosology.

PMID- 21960456
TI  - Moral and social reasoning in autism spectrum disorders.
AB  - This study compared moral and social reasoning in individuals with and without
      autism spectrum disorders (ASD). Ten familiar schoolyard transgressions were
      shown to 18 participants with and 18 participants without ASD. They judged the
      appropriateness of the behavior and explained their judgments. Analysis of the
      rationales revealed that participants with typical development used significantly
      more abstract rules than participants with ASD, who provided more nonspecific
      condemnations of the behaviors. Both groups judged social conventional
      transgressions to be more context-bound than moral transgressions, with this
      distinction more pronounced in typically developing individuals, who also
      provided significantly more examples of situations in which the depicted
      behaviors would be acceptable. The educational implications of these findings for
      individuals with ASD are discussed.

PMID- 21960457
TI  - Treatment discontinuation in patients with very early rheumatoid arthritis in
      sustained simplified disease activity index remission after synthetic disease
      modifying anti-rheumatic drug administration.
AB  - We aimed to identify whether drug-free remission could be achieved in patients
      with very early rheumatoid arthritis (RA) with poor prognosis factors by
      treatment with synthetic disease-modifying antirheumatic drugs (DMARDs). Thirteen
      patients with very early RA, whose disease was considered to have highly erosive
      potential, were included. Magnetic resonance imaging (MRI)-proven bone edema and
      autoantibodies were determined in these patients. A treat-to-target strategy
      initiated with synthetic DMARDs was employed for 12 months. If the patients
      achieved simplified disease activity index (SDAI) remission along with a
      reduction of the RA MRI scoring bone edema score to <33% as compared with
      baseline at 12 months, DMARD treatment was stopped and the clinical status was
      further observed for the following 12 months. Synthetic DMARDs were stopped at 12
      months in 5 patients. One of the 5 was lost to follow-up because of sustaining an
      injury that required orthopedic surgery. Three of the remaining 4 patients showed
      continued SDAI remission that was DMARD-free without any evidence of radiographic
      progression for the following 12 months. Although this was a small clinical
      trial, we have shown-for the first time-that true remission of very early RA with
      poor prognosis factors can be achieved by treatment with synthetic DMARDs.

PMID- 21960459
TI  - Use of a mouse model of pancreatic neuroendocrine tumors to find pericyte
      biomarkers of resistance to anti-angiogenic therapy.
AB  - The successful introduction of rationally targeted agents into standard cancer
      care is a testimony of the vast knowledge base in tumor biology. However, in
      order to provide individually tailored therapy to patients and to identify small
      subsets of patients with a high likelihood to benefit from treatment, the
      identification of biomarkers for response or resistance to a particular
      therapeutic regimen is imperative. Herein, by the use of a genetically engineered
      mouse model of pancreatic neuroendocrine tumors, we have assessed the utility of
      pericyte characteristics in terms of differential marker expression to serve as
      surrogate markers for response or evasive resistance to anti-angiogenic therapy.
      We found that tumors refractory to therapy following long-term treatment with a
      vascular endothelial growth factor receptor-2 blocking antibody contained blood
      vessels with a prolific investment of pericytes expressing alpha-smooth muscle
      actin. Further analysis by simultaneous immunostaining for different pericyte
      markers led to the conclusion that the increased abundance of this particular
      subtype of blood vessels most likely occurred by co-option of vessels from the
      surrounding exocrine pancreas. Our findings may form the basis for retrospective
      analysis of pancreatic neuroendocrine tumors from patients having undergone
      treatment with anti-angiogenic agents in order to validate the occurrence of
      pericytes expressing alpha-smooth muscle actin as a biomarker for tumors
      refractory to therapy.

PMID- 21960458
TI  - Seasonal changes in activities of human neutrophils in vitro.
AB  - OBJECTIVE AND DESIGN: We present a retrospective analysis of previously collected
      blood samples to determine whether the immune response of neutrophils depends on
      the season i.e., short versus long days, in which blood samples were collected.
      METHODS: The bactericidal activity and adhesive capacity of neutrophils, the
      production of reactive oxygen species (ROS), and CD11b/CD18 molecule expression
      level were investigated. The investigated neutrophils were divided into two
      groups based on the time of blood collection: the winter season with short days
      and the summer season with long days. RESULTS: We found seasonal variation in
      measurements of all the analyzed functional responses of neutrophils to stimuli.
      The strongest adhesion, as well as maximum values of ROS production, was
      presented by neutrophils isolated from the summer group. The highest bactericidal
      activity of neutrophils was also observed in blood donors from summer group.
      CONCLUSIONS: The magnitude of the immune functional activity of neutrophils
      varies with the season of the year and is decreased in winter.

PMID- 21960460
TI  - Physiological demands of mountain rescue work.
AB  - OBJECTIVE: To characterise the physical fitness of mountain rescue (MR)
      volunteers and the physical demands of a typical MR callout. METHODS: Eight MR
      volunteers (age +/- SD: 45.5 +/- 8.9 years) completed a laboratory-based
      treadmill exercise test to exhaustion. One week later subjects completed a field
      based simulated callout to retrieve a casualty by stretcher. In both studies
      exercise intensity was evaluated by determination of oxygen uptake and other
      cardiovascular measures. RESULTS: The maximal oxygen uptake of the participants
      was 53 ml/kg/min (95% CI 45 to 60). In an unassisted callout, a typical rucksack
      load was 17% of body mass. Ascent time was 56 min (95% CI 40 to 72), of which 82%
      (95% CI 66% to 98%) was completed at hard or very hard intensity (above the
      respiratory compensation point). Descent time with a stretcher was 58 min (95% CI
      52 to 64), of which only 6% (95% CI -4% to 16%) was completed at hard or very
      hard intensity. Correlations between heart rate and oxygen uptake were similar
      (p=0.254 by analysis of variance) during laboratory (r=0.72) and field testing,
      especially for the ascent (r=0.75). CONCLUSIONS: Mountain rescuers generally have
      high levels of physical fitness and are required to perform at very hard
      intensity for the majority of the ascent to a casualty. Heart rate is a simple
      yet valid measure of exercise intensity in MR personnel. These findings highlight
      important information on the unique physical demands faced by MR volunteers and
      provide direction for future research, volunteer selection and training.

PMID- 21960461
TI  - CO oxidation as a prototypical reaction for heterogeneous processes.
AB  - CO oxidation, although seemingly a simple chemical reaction, provides us with a
      panacea that reveals the richness and beauty of heterogeneous catalysis. The
      Fritz Haber Institute is a place where a multidisciplinary approach to study the
      course of such a heterogeneous reaction can be generated in house. Research at
      the institute is primarily curiosity driven, which is reflected in the five
      sections comprising this Review. We use an approach based on microscopic concepts
      to study the interaction of simple molecules with well-defined materials, such as
      clusters in the gas phase or solid surfaces. This approach often asks for the
      development of new methods, tools, and materials to prove them, and it is exactly
      this aspect, both, with respect to experiment and theory, that is a trade mark of
      our institute.

PMID- 21960462
TI  - Parotid abscess in a patient with obstructive sleep apnea treated with continuous
      positive airway pressure therapy.

PMID- 21960463
TI  - Influence of traffic variations on exposure to wireless signals in realistic
      environments.
AB  - In this article, the general public daily exposure to broadcast signals and
      Global System for Mobile Communications (GSM) or Universal Mobile
      Telecommunications System (UMTS) mobile telephone signals in indoor areas is
      investigated. Temporal variations and traffic distributions during a day at
      different indoor sites in urban and rural zones are presented. The goal is to
      analyze the real exposure compared to the maximum assessment imposed by radio
      protection standards and to characterize the ratio between daily and maximum
      theoretical values. Hence, a realistic maximum is proposed based on the
      statistical analysis performed using measurements. Broadcast signals remain
      constant over the day so they are best fitted with a Normal distribution while
      the mobile telephone signals depend on the traffic demand during the day so they
      fit a three-Gaussian distribution model. A general mask is also constructed for
      underlining the maximum equivalent active traffic for different periods in the
      day. Also, relations between the mean values over 24 h, the realistic maximal
      values (at 99%) and the maximal theoretical values are presented. The realistic
      maximum is also presented with a sliding time average of 6 min applied to the
      measurements in accordance with international standards. An extrapolation factor
      is given for the different systems to easily assess the maximum values starting
      from an instantaneous measurement. The extrapolation factor is also given for a
      broadband measurement to estimate the maximum potential exposure during the day.

PMID- 21960464
TI  - Structural mechanisms of constitutive activation in the C5a receptors with
      mutations in the extracellular loops: molecular modeling study.
AB  - Previously we demonstrated by random saturation mutagenesis a set of mutations in
      the extracellular (EC) loops that constitutively activate the C5a receptor (C5aR)
      (Klco et al., Nat Struct Mol Biol 2005;12:320-326; Klco et al., J Biol Chem
      2006;281:12010-12019). In this study, molecular modeling revealed possible
      conformations for the extracellular loops of the C5a receptors with mutations in
      the EC2 loop or in the EC3 loop. Comparison of low-energy conformations of the EC
      loops defined two distinct clusters of conformations typical either for strongly
      constitutively active mutants of C5aR (the CAM cluster) or for nonconstitutively
      active mutants (the non-CAM cluster). In the CAM cluster, the EC3 loop was turned
      towards the transmembrane (TM) helical bundle and more closely interacted with
      EC2 than in the non-CAM cluster. This suggested a structural mechanism of
      constitutive activity where EC3 contacts EC2 leading to EC2 interactions with
      helix TM3, thus triggering movement of TM7 towards TM2 and TM3. The movement
      initiates rearrangement of the system of hydrogen bonds between TM2, TM3 and TM7
      including formation of the hydrogen bond between the side chains of D82(2.50) in
      TM2 and N296(7.49) in TM7, which is crucial for formation of the activated states
      of the C5a receptors (Nikiforovich et al., Proteins: Struct Funct Gene
      2011;79:787-802). Since the relative large length of EC3 in C5aR (13 residues) is
      comparable with those in many other members of rhodopsin family of GPCRs (13-19
      residues), our findings might reflect general mechanisms of receptor constitutive
      activation. The very recent X-ray structure of the agonist-induced constitutively
      active mutant of rhodopsin (Standfuss et al., Nature 2011;471:656-660) is
      discussed in view of our modeling results.

PMID- 21960465
TI  - Gadoxetic acid disodium-enhanced hepatocyte phase MRI: can increasing the flip
      angle improve focal liver lesion detection?
AB  - PURPOSE: To determine whether hepatocyte phase gadoxetic acid disodium (EOB)
      enhanced MRI using a high flip angle (FA) improves focal liver lesion (FLL)
      detection compared with using a standard low FA. MATERIALS AND METHODS: Sixty-two
      consecutive patients with 159 FLLs underwent EOB-enhanced MRI during the
      hepatocyte phase at 5, 10, 15, and 20 min, with both low (10 degrees ) and high
      (30 degrees ) FAs. Two blinded radiologists independently and randomly reviewed
      the two image sets using a four-point rating scale. Sensitivities and
      specificities were calculated and lesion-to-liver contrast ratio (LLC) on all
      hepatocyte phase images was measured. RESULTS: The sensitivities with high FA for
      small (<=10 mm) malignant FLLs were significantly higher than those with low FA,
      at all time points, for both readers (P <= 0.05). Meanwhile, the specificities of
      the two protocols for the detection of all FLLs at all time points during the
      hepatocyte phase were high and same (98.2%) for both readers, without any
      significant differences (P = 1.00). LLCs with high FA were significantly higher
      than those with low FA at all time points (P <= 0.001). CONCLUSION: Hepatocyte
      phase EOB-enhanced MRI with increasing FA can significantly increase LLC and
      improve the detection of FLLs, particularly small malignant lesions.

PMID- 21960466
TI  - A novel human hepatoma cell line, FLC-4, exhibits highly enhanced liver
      differentiation functions through the three-dimensional cell shape.
AB  - We characterized three-dimensional human hepatoma cell lines, functional liver
      cell (FLC) cell lines, to establish a highly differentiated hepatoma cell line.
      We investigated the effect of extracellular matrix and cell morphology on liver
      specific gene expression in FLC cells. The hepatocyte nuclear factor-4alpha (HNF
      4alpha) and other liver-specific gene expressions were enhanced in spherical FLC
      4 cells on EHS-gel, but other human hepatoma cells such as HepG2 did not show the
      enhancement. Importantly, the liver-specific gene expression levels in spherical
      FLC-4 cells cultured on EHS-gel were comparable to those of human liver and were
      much higher than those of other human hepatoma cell lines. The major matrix
      components and growth factors in EHS-gel did not affect cell shape and liver
      functions. To exclude any effect of the extracellular matrix, we made spherical
      FLC-4 cells by actin filament disruption. The actin-disrupted spherical cells
      also showed an enhanced liver-specific gene expression. We concluded that three
      dimensional cell shape per se is one of the most important determinants of liver
      differentiation functions in FLC-4 cells. Cell morphology-dependent induction of
      liver-specific gene expression was mediated through microtubule organization. In
      conclusion, differentiation of FLC-4 human hepatoma cell line can be enhanced to
      a human liver-like level through the three-dimensional cell shape in a
      microtubule-dependent manner.

PMID- 21960467
TI  - Reduction potentials and acidity constants of Mn superoxide dismutase calculated
      by QM/MM free-energy methods.
AB  - We used two theoretical methods to estimate reduction potentials and acidity
      constants in Mn superoxide dismutase (MnSOD), namely combined quantum mechanical
      and molecular mechanics (QM/MM) thermodynamic cycle perturbation (QTCP) and the
      QM/MM-PBSA approach. In the latter, QM/MM energies are combined with continuum
      solvation energies calculated by solving the Poisson-Boltzmann equation (PB) or
      by the generalised Born approach (GB) and non-polar solvation energies calculated
      from the solvent-exposed surface area. We show that using the QTCP method, we can
      obtain accurate and precise estimates of the proton-coupled reduction potential
      for MnSOD, 0.30+/-0.01 V, which compares favourably with experimental estimates
      of 0.26-0.40 V. However, the calculated potentials depend strongly on the DFT
      functional used: The B3LYP functional gives 0.6 V more positive potentials than
      the PBE functional. The QM/MM-PBSA approach leads to somewhat too high reduction
      potentials for the coupled reaction and the results depend on the solvation model
      used. For reactions involving a change in the net charge of the metal site, the
      corresponding results differ by up to 1.3 V or 24 pK(a) units, rendering the
      QM/MM-PBSA method useless to determine absolute potentials. However, it may still
      be useful to estimate relative shifts, although the QTCP method is expected to be
      more accurate.

PMID- 21960468
TI  - Adherence to use of a home-based exercise DVD in people with Huntington disease:
      participants' perspectives.
AB  - BACKGROUND: Individualized exercise instruction on a regular basis may be
      desirable for people with Huntington disease (HD). Sustained interventions,
      however, may not be the most feasible for lifelong disease management. It is
      critical, therefore, for physical therapists to find ways to facilitate
      engagement in independent exercise programs. The capabilities of DVD technology
      can make the DVD a useful format to facilitate engagement for people with HD who
      have motivational and cognitive problems. OBJECTIVE: The purpose of this study
      was to explore how people with HD used a home-based exercise DVD and how it was
      perceived by the participants and their caregivers. DESIGN: An exploratory, mixed
      method design was used in this study. METHODS: Fifteen participants with HD were
      provided with an exercise DVD, developed by the authors, to support their
      engagement in a home-based exercise program. Exercise diaries were used to record
      adherence rates. Semistructured interviews were conducted to explore what factors
      affected the usability of the DVD. Conversations were audio recorded and fully
      transcribed. Content analysis approach was used to analyze the interviews.
      RESULTS: Most of the participants (11/15, 73.3%) adhered well to the use of the
      DVD. Participants felt that the exercises were suitable. Commitment of the
      caregiver as a key to the success of the program was the main theme that emerged
      from the data. Participants identified barriers and facilitators that affected
      adherence to using the exercise DVD and described management strategies that
      helped promote adherence to the exercise program. CONCLUSIONS: The DVD was
      perceived to be suitable and supportive. The DVD could be appropriate for use in
      supporting people with HD to engage in exercise at home, either outside of
      therapy sessions or upon completion of a therapy program.

PMID- 21960469
TI  - Gold-catalyzed [3+2] cycloaddition/hydrolytic Michael addition/retro-aldol
      reactions of propargylic esters tethered to cyclohexadienones.

PMID- 21960470
TI  - How many ionizable groups can sit on a protein hydrophobic core?
AB  - Full or partial burial of ionizable groups in the hydrophobic interior of
      proteins underlies the large modulation in group properties (modified pK value,
      high nucleophilicity, enhanced capability of interaction with chemical moieties
      of the substrate, etc.) linked to biological function. Indeed, the few internal
      ionizable residues found in proteins are known to play important functional roles
      in catalysis and, in general, in energy transduction processes. However,
      ionizable-group burial is expected to be seriously disruptive and, it is
      important to note, most functional sites contain not just one, but several
      ionizable residues. Hence, the adaptations involved in the development of
      function in proteins (through in vitro engineering or during the course of
      natural evolution) are not fully understood. Here, we explore experimentally how
      proteins respond to the accumulation of hydrophobic-to-ionizable residue
      substitutions. For this purpose, we have constructed a combinatorial library
      targeting a hydrophobic cluster in a consensus-engineered, stabilized form of a
      small model protein. Contrary to naive expectation, half of the variants randomly
      selected from the library are soluble, folded, and active, despite including up
      to four mutations. Furthermore, for these variants, the dependence of stability
      with the number of mutations is not synergistic and catastrophic, but smooth and
      approximately linear. Clearly, stabilized protein scaffolds may be robust enough
      to withstand many disruptive hydrophobic-to-ionizable residue mutations, even
      when they are introduced in the same region of the structure. These results
      should be relevant for protein engineering and may have implications for the
      understanding of the early evolution of enzymes.

PMID- 21960471
TI  - Insights into uranyl chemistry from molecular dynamics simulations.
AB  - First-principles and purely classical molecular dynamics (MD) simulations for
      complexes of the uranyl ion (UO(2)(2+)) are reviewed. Validation of Car
      Parrinello MD simulations for small uranyl complexes in aqueous solution is
      discussed. Special attention is called to the mechanism of ligand-exchange
      reactions at the uranyl centre and to effects of solvation and hydration on
      coordination and structural properties. Large-scale classical MD simulations are
      surveyed in the context of liquid-liquid extraction, with uranyl complexes
      ranging from simple hydrates to calixarenes, and nonaqueous phases from simple
      organic solvents and supercritical CO(2) to ionic liquids.

PMID- 21960472
TI  - A brief guide to designing effective figures for the scientific paper.

PMID- 21960473
TI  - Nanocone tip-film solar cells with efficient charge transport.

PMID- 21960474
TI  - A graphene-conjugated oligomer hybrid probe for light-up sensing of lectin and
      Escherichia coli.

PMID- 21960475
TI  - Overcoming the water vulnerability of electronic devices: a highly water
      resistant ZnO nanodevice with multifunctionality.

PMID- 21960476
TI  - Electronic control of cell detachment using a self-doped conducting polymer.

PMID- 21960478
TI  - Flexible plasmonics on unconventional and nonplanar substrates.

PMID- 21960479
TI  - Tailored microcrystal growth: a facile solution-phase synthesis of gold rings.

PMID- 21960480
TI  - Dynamic covalent chemistry on surfaces employing highly reactive cyclopentadienyl
      moieties.

PMID- 21960481
TI  - Silver nanowire-polymer composite electrodes for efficient polymer solar cells.

PMID- 21960482
TI  - Structural and molecular biology of type I galactosemia: disease-associated
      mutations.
AB  - Type I galactosemia results from reduced galactose 1-phosphate
      uridylyltransferase (GALT) activity. Signs of disease include damage to the eyes,
      brain, liver, and ovaries. However, the exact nature and severity of the
      pathology depends on the mutation(s) in the patient's genes and his/her
      environment. Considerable enzymological and structural knowledge has been
      accumulated and this provides a basis to explain, at a biochemical level,
      impairment in the enzyme in the more than 230 disease-associated variants, which
      have been described. The most common variant, Q188R, occurs close to the active
      site and the dimer interface. The substitution probably disrupts both UDP-sugar
      binding and homodimer stability. Other alterations, for example K285N, occur
      close to the surface of the enzyme and most likely affect the folding and
      stability of the enzyme. There are a number of unanswered questions in the field,
      which require resolution. These include the possibility that the main enzymes of
      galactose metabolism form a supramolecular complex and the need for a high
      resolution crystal structure of human GALT.

PMID- 21960483
TI  - A 'bloody' hot stew.

PMID- 21960484
TI  - Novel solid-state polymer electrolyte of colloidal crystal decorated with ionic
      liquid polymer brush.

PMID- 21960485
TI  - 2011 ACCF/AHA focused update of the guideline for the management of patients with
      peripheral artery disease (updating the 2005 guideline): a report of the American
      College of Cardiology Foundation/American Heart Association Task Force on
      Practice Guidelines: developed in collaboration with the Society for
      Cardiovascular Angiography and Interventions, Society of Interventional
      Radiology, Society for Vascular Medicine, and Society for Vascular Surgery.

PMID- 21960486
TI  - Mechanism for gene control by a natural allosteric group I ribozyme.
AB  - An allosteric ribozyme consisting of a metabolite-sensing riboswitch and a group
      I self-splicing ribozyme was recently found in the pathogenic bacterium
      Clostridium difficile. The riboswitch senses the bacterial second messenger c-di
      GMP, thereby controlling 5'-splice site choice by the downstream ribozyme. The
      proximity of this allosteric ribozyme to the open reading frame (ORF) for CD3246
      suggests that coenzyme-mediated regulation of splicing controls expression of
      this putative virulence gene. In the presence of c-di-GMP, the allosteric
      ribozyme in the CD3246 precursor transcript generates a spliced transcript that
      retains the riboswitch aptamer. In the absence of c-di-GMP, the ribozyme mediates
      an alternative GTP attack that results in a truncated transcript (alternative GTP
      attack product). Using reporter assays in Escherichia coli, we investigated the
      difference in gene expression between the spliced product and the alternative GTP
      attack product. We provide evidence that CD3246 gene expression is activated if
      allosteric ribozyme splicing creates a ribosome binding site (RBS) for
      translation from a UUG start codon. In addition, biochemical and genetic analyses
      reveal that the riboswitch may further control CD3246 expression by revealing or
      occluding this newly formed RBS. Therefore, this architecture provides the
      riboswitch with a mechanism for extended regulation after splicing has occurred
      or as a backup mechanism for suppression of translation in the event of
      misregulated splicing.

PMID- 21960487
TI  - Cryo-electron microscopy structure of the 30S subunit in complex with the YjeQ
      biogenesis factor.
AB  - YjeQ is a protein broadly conserved in bacteria containing an N-terminal
      oligonucleotide/oligosaccharide fold (OB-fold) domain, a central GTPase domain,
      and a C-terminal zinc-finger domain. YjeQ binds tightly and stoichiometrically to
      the 30S subunit, which stimulates its GTPase activity by 160-fold. Despite
      growing evidence for the involvement of the YjeQ protein in bacterial 30S subunit
      assembly, the specific function and mechanism of this protein remain unclear.
      Here, we report the costructure of YjeQ with the 30S subunit obtained by cryo
      electron microscopy. The costructure revealed that YjeQ interacts simultaneously
      with helix 44, the head and the platform of the 30S subunit. This binding
      location of YjeQ in the 30S subunit suggests a chaperone role in processing of
      the 3' end of the rRNA as well as in mediating the correct orientation of the
      main domains of the 30S subunit. In addition, the YjeQ binding site partially
      overlaps with the interaction site of initiation factors 2 and 3, and upon
      binding, YjeQ covers three inter-subunit bridges that are important for the
      association of the 30S and 50S subunits. Hence, our structure suggests that YjeQ
      may assist in ribosome maturation by preventing premature formation of the
      translation initiation complex and association with the 50S subunit. Together,
      these results support a role for YjeQ in the late stages of 30S maturation.

PMID- 21960488
TI  - Multimodal imaging of spike propagation: a technical case report.
AB  - We report an 11-year-old boy with intractable epilepsy, who had cortical
      dysplasia in the right superior frontal gyrus. Spatiotemporal source analysis of
      MEG and EEG spikes demonstrated a similar time course of spike propagation from
      the superior to inferior frontal gyri, as observed on intracranial EEG. The
      tractography reconstructed from DTI showed a fiber connection between these
      areas. Our multimodal approach demonstrates spike propagation and a white matter
      tract guiding the propagation.

PMID- 21960489
TI  - Systematic differences between lean and obese adolescents in brain spin-lattice
      relaxation time: a quantitative study.
AB  - BACKGROUND AND PURPOSE: Emerging evidence suggests that obese adolescents show
      changes in brain structure compared with lean adolescents. In addition, obesity
      impacts body development during adolescence. We tested a hypothesis that T1, a
      marker of brain maturation, can show brain differences associated with obesity.
      MATERIALS AND METHODS: Adolescents similar in sex, family income, and school
      grade were recruited by using strict entry criteria. We measured brain T1 in 48
      obese and 31 lean adolescents by quantitative MR imaging at 1.5T. We combined
      MPRAGE and inversion-recovery sequences with normalization to standard space and
      automated skull stripping to obtain T1 maps with a symmetric voxel volume of 1
      mm(3). RESULTS: Sex, income, triglycerides, total cholesterol, and fasting
      glucose did not differ between groups, but obese adolescents had significantly
      lower HDL, higher LDL, and higher fasting insulin levels than lean adolescents.
      Intracranial vault volume did not differ between groups, but obese adolescents
      had smaller intracranial vault-adjusted brain parenchymal volumes. Obese
      adolescents had 4 clusters (>100 contiguous voxels) of T1 relaxation that were
      significantly different (P < .005) from those in lean adolescents. Three of these
      clusters had longer T1s in obese adolescents (in the orbitofrontal and parietal
      regions), and 1 cluster had shorter T1s, compared with lean adolescents.
      CONCLUSIONS: Our results suggest that obesity may have a significant impact on
      brain development, especially in the frontal and parietal lobes. It is unclear if
      these changes persist into adulthood or whether they indicate that obese subjects
      follow a different developmental trajectory during adolescence.

PMID- 21960490
TI  - The use of Onyx in different types of intracranial dural arteriovenous fistula.
AB  - BACKGROUND AND PURPOSE: Recently some series have been published about the use of
      Onyx for the treatment of DAFVs with satisfactory results. Our aim was to
      describe the treatment of different types of intracranial DAVFs with
      transcatheter injection of Onyx through an arterial approach. MATERIALS AND
      METHODS: At the Department of Interventional Neuroradiology, Hospital
      Lariboisiere Paris, between January 2005 and January 2010, we treated 44 DAVFs in
      42 patients. All patients were initially treated by arterial injection of Onyx.
      The average patient age was 56 years (range, 27-86 years), and there were 17
      women and 25 men treated. RESULTS: A total of 58 arterial pedicles were
      catheterized, with the middle meningeal artery representing the most common site
      (n = 38). The average time of injection was 30 minutes (range, 15-60 minutes),
      and the average amount of Onyx was 2.5 mL (range, 0.6-6.5 mL). Of the 20 fistulas
      with direct venous drainage into a dural sinus (types I and II), we achieved the
      preservation of the sinus in 7 patients. Of the 44 fistulas embolized, 8 required
      a second embolization treatment and 1 fistula required a third treatment. In 9
      cases, a complementary treatment was performed via transvenous embolization with
      coils and/or open surgery. Early complications were observed in 6 patients: Four
      had nerve injury (facial palsy, n = 2, and neuralgia, n = 2), and 2 had
      complications related to extension of venous thrombosis postembolization. All 6
      patients had partial or complete resolution of these symptoms. CONCLUSIONS: The
      treatment of DAVFs by intracranial arterial injection of Onyx is safe, and, in
      most cases, results in the occlusion of the arterial venous shunt. In DAVFs with
      direct sinus drainage, sinus preservation was only possible in 7 of 20 patients
      (35%).

PMID- 21960491
TI  - Deep medullary vein involvement in neonates with brain damage: an MR imaging
      study.
AB  - BACKGROUND AND PURPOSE: Different and specific MR imaging patterns of lesions
      involving WM are widely defined in neonatal encephalopathy. The aim of this study
      was to describe a novel MR imaging pattern of damage characterized by the
      abnormal prominence of DMVs in premature and full-term neonates. MATERIALS AND
      METHODS: Twenty-one (11 premature and 10 full-term) neonates with MR imaging
      evidence of linear radially oriented fan-shaped lesions in the periventricular WM
      and without dural venous thrombosis were enrolled in this retrospective study. A
      total of 37 MR imaging examinations were performed at ages ranging from day 0 to
      24 months. RESULTS: According to the appearance of linear anomalies on T2
      weighted images, we identified 2 main patterns: T2 hypointense lesions without WM
      cavitations and T2 hypointense lesions associated with linear cysts. The first
      pattern was found in 17 examinations performed between 0 and 44 days of life; the
      second pattern was found in another 14 examinations performed between 6 days and
      4 months of life. Five examinations performed between 9 and 24 months of life
      showed a reduction in volume and hyperintense signal intensity of the
      periventricular WM on T2-weighted and FLAIR images. CONCLUSIONS: Subtle linear WM
      lesions with the same anatomic distribution of DMVs may be evident in premature
      and full-term neonates without signs of major venous thrombosis, both in the
      acute and subacute phases. Their appearance and evolution suggest that transient
      DMV engorgement/thrombosis may be responsible for WM damage that can lead to a
      PVL-like pattern.

PMID- 21960492
TI  - Erdheim-Chester disease of the central nervous system: new manifestations of a
      rare disease.
AB  - BACKGROUND AND PURPOSE: ECD is a rare non-Langerhans-cell histiocytosis, which
      can involve the CNS; therefore, CNS imaging findings have been described in only
      a small number of patients. To gain additional insight into the CNS
      manifestations of ECD, we reviewed the findings on imaging of the brain, head and
      neck, and spine in patients with ECD who presented to our institution. Here, we
      illustrate manifestations that have not, to our knowledge, been previously
      described. MATERIALS AND METHODS: CT, MR imaging, and PET/CT studies of the
      brain, maxillofacial region, and spine were reviewed in 11 patients with ECD.
      RESULTS: Four new manifestations of ECD were present, including the following: a
      stellate appearance of intracranial extra-axial lesions, ependymal enhancement
      along the lateral ventricle with deep linear extension to the lentiform nucleus,
      irregular enhancement in the pons, and diffuse involvement of the vertebral
      column on PET/CT. CONCLUSIONS: ECD has a variety of imaging appearances in the
      CNS, including new manifestations described herein. Neuroradiologists should be
      aware of these manifestations to avoid mistaking them for other disease
      processes.

PMID- 21960493
TI  - High signal intensity on T2-weighted MR imaging at term-equivalent age in preterm
      infants does not predict 2-year neurodevelopmental outcomes.
AB  - BACKGROUND AND PURPOSE: DEHSI on T2-weighted MR imaging in preterm infants at
      term-equivalent age has been regarded as an unfavorable marker for
      neurodevelopmental outcome. The aim of this study was to examine the relationship
      between the presence and extent of DEHSI and neurodevelopmental outcomes.
      MATERIALS AND METHODS: We evaluated the MR images of 160 preterm infants at term
      equivalent age. The presence of DEHSI was evaluated in separate regions and
      classified into 5 grades based on the extent of DEHSI. We also examined within
      those infants with DEHSI, whether typical signal-intensity characteristics of the
      posterior periventricular crossroads region were visible. Finally, ADC and FA
      values within the white matter were analyzed. Neurodevelopmental outcomes were
      assessed at 2-year corrected age with a standardized neurologic examination and
      the BSID-II. RESULTS: The grade of DEHSI had significant linear trends with
      increasing ADC and a trend toward lower FA values. However, there was no
      relationship between the degree of DEHSI and 2-year neurodevelopmental outcomes.
      In contrast, 13 infants with DEHSI who did not have visible posterior crossroads
      had poorer neurodevelopmental outcomes compared with infants with visible
      posterior crossroads. CONCLUSIONS: Although DEHSI may represent disturbances in
      white matter structure, as illustrated by its relationship to altered ADC and FA
      values, there is no relationship to short-term neurodevelopment outcome unless
      there are invisible posterior crossroads, representing a severe form of global
      high T2 signal intensity.

PMID- 21960494
TI  - Tintin and colleagues go to the doctor.

PMID- 21960495
TI  - Using quantitative CT perfusion for evaluation of delayed cerebral ischemia
      following aneurysmal subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: DCI is a serious complication following aneurysmal SAH
      leading to permanent neurologic deficits, infarction, and death. Our aim was to
      prospectively evaluate the diagnostic accuracy of CTP and to determine a
      quantitative threshold for DCI in aneurysmal SAH. MATERIALS AND METHODS: Patients
      with SAH were prospectively enrolled in a protocol approved by the institutional
      review board. CTP was performed during the typical time period for DCI, between
      days 6 and 8 following SAH. Quantitative CBF, CBV, and MTT values were obtained
      by using standard region-of-interest placement sampling of gray matter. The
      reference standard for DCI is controversial and consisted of clinical and imaging
      criteria in this study. In a subanalysis of vasospasm, DSA was used as the
      reference standard. ROC curves determined the diagnostic accuracy by using AUC.
      Optimal threshold values were calculated by using the patient population utility
      method. RESULTS: Ninety-seven patients were included; 41% (40/97) had DCI.
      Overall diagnostic accuracy was 93% for CBF, 88% for MTT, and 72% for CBV.
      Optimal threshold values were 35 mL/100 g/min (90% sensitivity, 68% specificity)
      for CBF and 5.5 seconds (73% sensitivity, 79% specificity) for MTT. In the
      subanalysis (n = 57), 63% (36/57) had vasospasm. Overall diagnostic accuracy was
      94% for CBF, 85% for MTT, and 72% for CBV. Optimal threshold values were 36.5
      mL/100 g/min (95% sensitivity, 70% specificity) for CBF and 5.4 seconds (78%
      sensitivity, 70% specificity) for MTT. CONCLUSIONS: CBF and MTT have the highest
      overall diagnostic accuracy. Threshold values of 35 mL/100 g/min for CBF and 5.5
      second MTT are suggested for DCI on the basis of the patient population utility
      method. Absolute threshold values may not be generalizable due to differences in
      scanner equipment and postprocessing methods.

PMID- 21960496
TI  - Decreased gray matter concentration and local synchronization of spontaneous
      activity in the motor cortex in Duchenne muscular dystrophy.
AB  - BACKGROUND AND PURPOSE: Patients with DMD have demonstrated functional
      abnormalities in the motor-related brain areas in previous PET, MRS, and TMS
      studies. We applied structural MR imaging and RS-fMRI in patients with DMD for
      the first time, and aimed to investigate the GMC and ReHo or local
      synchronization of spontaneous activity in the motor cortex. MATERIALS AND
      METHODS: Ten boys with DMD (6.4-14.0 years of age) and 15 healthy controls (7.9
      15.1 years of age) underwent brain structural MR imaging and RS-fMRI scanning.
      GMC and local synchronization of spontaneous activity in the motor cortex were
      analyzed by using VBM and ReHo approaches, respectively. RESULTS: Compared with
      healthy controls, boys with DMD showed decreased GMC in the left PSMC and
      decreased ReHo in the bilateral PMSC as well as in the supplementary motor area
      (P < .05, corrected). CONCLUSIONS: The current results indicate that boys with
      DMD have both GMC loss and decreased local synchronization of spontaneous
      activity in the motor cortex, which might be due to the deficiency of dystrophin
      in the brain.

PMID- 21960497
TI  - Clinical and radiologic findings of inner ear involvement in sickle cell disease.
AB  - BACKGROUND AND PURPOSE: SCD has been reported to involve the inner ear and result
      in LH and LO. Our purpose was to examine the prevalence of inner ear involvement
      and to assess the relationship between clinical and imaging findings in patients
      with SCD. MATERIALS AND METHODS: Review of our institution's imaging data base
      for patients with SCD who underwent imaging of the brain or head and neck region
      or both by CT, MR, or both from 2004 to 2008 was performed. Presenting symptoms,
      type of SCD, sex, imaging studies performed, and imaging findings were
      documented. RESULTS: Among 89 patients with SCD identified (41 males, 48
      females), 17 patients (14 males, 3 females; 10-48 years old) underwent imaging
      evaluation for inner ear complaints, including SNHL, dizziness, vertigo, and
      tinnitus. LH was identified in 3 patients (3 males) and LO was identified in
      another 3 patients (2 males, 1 female). All patients with LH had sickle
      hemoglobin C disease, whereas those with LO consisted of 2 patients homozygous
      for HbS (2) and 1 with HbS/beta-thalassemia. Patients with LH presented with
      vestibular symptoms (2 vertigo, 1 dizziness), whereas patients with LO presented
      with SNHL. LH was seen in the basal turn of cochlea and vestibule, whereas LO
      involved the lateral semicircular canal. CONCLUSIONS: LH and LO were found in
      approximately one-third of patients with SCD with inner ear symptoms and
      preferentially affected males.

PMID- 21960498
TI  - Pituicytoma, spindle cell oncocytoma, and granular cell tumor: clarification and
      meta-analysis of the world literature since 1893.
AB  - BACKGROUND AND PURPOSE: Pituicytoma, SCO, and GCT are poorly understood entities
      with confusing nomenclature and undetermined imaging characteristics. Our purpose
      was to confirm published cases of pituicytoma, SCO, and GCT with the newest 2007
      World Health Organization criteria and elucidate imaging findings that
      distinguish these tumors from common entities such as pituitary adenoma.
      MATERIALS AND METHODS: A literature search identified 145 published cases (81
      GCTs, 48 pituicytomas, and 16 SCOs). Case diagnoses were blindly reviewed by a
      neuropathologist according to the latest WHO criteria, resulting in 112
      pathologically documented cases (64 GCTs, 35 pituicytomas, and 13 SCOs). Imaging
      illustrations from proved cases were reviewed to determine location,
      configuration, attenuation and signal intensity, and enhancement characteristics.
      RESULTS: Only pituicytomas presented as purely intrasellar lesions (7/33). Most
      GCTs were purely suprasellar (28/45). All SCOs were both intra- and suprasellar
      (13/13). Twenty-five percent of pituicytomas (6/22) and GCTs (7/30) appeared
      separate from the pituitary gland. All SCOs were infiltrating. Seventy-nine
      percent of entities appeared isointense to brain on T1-weighted image (34/43).
      Seventy-four percent of pituicytomas enhanced homogeneously (14/19). Twelve of 23
      GCTs and 5/7 SCOs enhanced heterogeneously. Most GCTs were hyperattenuated to
      brain on CT (18/20). Eleven of 13 cases enhanced homogeneously. Visual
      disturbances were common symptoms for all entities (67/112). Diabetes insipidus
      was rare (4/112). CONCLUSIONS: Pituicytoma may be considered for purely
      intrasellar masses that are clearly separate from the pituitary gland. GCT should
      receive consideration for purely suprasellar lesions that are hyperattenuated to
      brain on CT. SCO should be considered for infiltrating pituitary masses with a
      mixed intra- and suprasellar location. A history of diabetes insipidus helps to
      exclude these tumors.

PMID- 21960499
TI  - Higher degrees of recanalization after mechanical thrombectomy for acute stroke
      are associated with improved outcome and decreased mortality: pooled analysis of
      the MERCI and Multi MERCI trials.
AB  - BACKGROUND AND PURPOSE: Although the combined end point of partial and complete
      recanalization is a well-established predictor of good outcome following acute
      stroke intervention, few investigations have evaluated the effect of the degree
      of recanalization. We hypothesized that greater degrees of recanalization would
      be associated with a higher likelihood of favorable functional outcomes.
      MATERIALS AND METHODS: Data from MERCI and Multi MERCI-prospective single-arm
      trials of endovascular mechanical thrombectomy for acute stroke-were pooled. The
      TIMI score was used to define the degree of recanalization, and a favorable
      outcome was defined as an mRS score of 0-2 at 90 days. RESULTS: A total of 305
      patients were included. Age, stroke severity, and site of arterial occlusion did
      not differ among groups stratified by the TIMI score. The unadjusted OR for a
      favorable outcome increased significantly as the TIMI score increased from 0 to 1
      (OR, 5.9; 95% CI, 1.7-20.0; P = .007) and from 2 to 3 (OR. 2.3; 95% CI, 1.2-4.5;
      P = .01) and the likelihood of death decreased significantly as the TIMI score
      increased from 2 to 3 (OR, 2.2; 95% CI, 1.1-4.3; P = .05). In multivariate
      analysis, each increase in TIMI grade increased the odds of a good outcome 2.6
      fold (95% CI, 1.9-3.4, P < .0001). CONCLUSIONS: Increases in the TIMI score were
      highly associated with improved outcomes. This finding not only provides
      additional evidence that restoration of blood flow improves clinical outcomes in
      ischemic stroke but also suggests that interventionalists should strive for
      complete revascularization when they provide endovascular treatment for acute
      ischemic stroke.

PMID- 21960500
TI  - The industry of CT scanning.

PMID- 21960501
TI  - Applicability of tableside flat panel detector CT parenchymal cerebral blood
      volume measurement in neurovascular interventions: preliminary clinical
      experience.
AB  - BACKGROUND AND PURPOSE: CBV is a vital perfusion parameter in estimating the
      viability of brain parenchyma (eg, in cases of ischemic stroke or after
      interventional vessel occlusion). Recent technologic advances allow parenchymal
      CBV imaging tableside in the angiography suite just before, during, or after an
      interventional procedure. The aim of this work was to analyze our preliminary
      clinical experience with this new imaging tool in different neurovascular
      interventions. MATERIALS AND METHODS: FPD-CBV measurement was performed on a
      biplane FPD angiographic system. Eighteen patients (11 women, 7 men) were
      examined (age range, 18-86 years; median, 58.7 years). In the 10 patients with
      stroke, the extent of intracranial hypoperfusion was evaluated. The remaining 8
      patients had an intracranial hemorrhage; periprocedural CBV was evaluated during
      the course of interventional treatment. RESULTS: In the 18 cases studied, 23 CBV
      measurements were performed. Twenty acquisitions were of sufficient diagnostic
      quality. The remaining 3 acquisitions failed technically, 1 due to motion
      artifacts and 2 due to injection technique and/or hardware failure. CONCLUSIONS:
      FPD-CBV measurement in the angiography suite provides a feasible and helpful tool
      for peri-interventional neuroimaging. It extends the intraprocedural imaging
      modalities to the level of tissue perfusion. However, the technique has technical
      limitations and shows room for improvement in the future.

PMID- 21960502
TI  - CT analysis demonstrates that cochlear height does not change with age.
AB  - BACKGROUND AND PURPOSE: CH measurements can often be useful in the diagnosis of
      inner ear malformations associated with SNHL. Our aim was to establish the
      relationship between CH and age by using analysis of CT images in patients who
      underwent coronal CT scans of the temporal bone between 2001 and 2007. MATERIALS
      AND METHODS: We measured CH on coronal CT scans of the temporal bone of 422 ears
      scanned from 2001 to 2007 in 211 patients, 1 month to 23 years of age. Using
      multivariate linear regression analysis, we determined the relationship of CH to
      age, sex, and HL type. In addition, 11 patients with multiple scans at different
      ages were assessed for change in CH with age. RESULTS: Average CH was 5.3 mm
      (normal range, 4.4-6.2 mm). Analysis showed no statistically significant change
      in CH across ages from 1 month to 23 years (95% CI for regression line slope = 
      0.003, 0.013). Likewise, there were no statistically significant differences in
      CH for patients with multiple scans at different ages. ICW increased with age as
      expected with increased cranial size. A small difference in CH between sexes was
      noted with males having greater CHs than females (P < .01). All patients with
      hypoplastic cochleas, defined by a CH <2 SDs from the mean (4.48 mm for males and
      4.25 mm for females), had HL with a positive predictive value of 86%.
      CONCLUSIONS: CH does not change from 1 month of age to adulthood and is slightly
      greater in males than in females.

PMID- 21960503
TI  - Quantitative blood flow measurements in gliomas using arterial spin-labeling at
      3T: intermodality agreement and inter- and intraobserver reproducibility study.
AB  - BACKGROUND AND PURPOSE: QUASAR is a particular application of the ASL method and
      facilitates the user-independent quantification of brain perfusion. The purpose
      of this study was to assess the intermodality agreement of TBF measurements
      obtained with ASL and DSC MR imaging and the inter- and intraobserver
      reproducibility of glioma TBF measurements acquired by ASL at 3T. MATERIALS AND
      METHODS: Two observers independently measured TBF in 24 patients with
      histologically proved glioma. ASL MR imaging with QUASAR and DSC MR imaging were
      performed on 3T scanners. The observers placed 5 regions of interest in the solid
      tumor on rCBF maps derived from ASL and DSC MR images and 1 region of interest in
      the contralateral brain and recorded the measured values. Maximum and average
      sTBF values were calculated. Intermodality and intra- and interobsever agreement
      were determined by using 95% Bland-Altman limits of agreement and ICCs. RESULTS:
      The intermodality agreement for maximum sTBF was good to excellent on DSC and ASL
      images; ICCs ranged from 0.718 to 0.884. The 95% limits of agreement ranged from
      59.2% to 65.4% of the mean. ICCs for intra- and interobserver agreement for
      maximum sTBF ranged from 0.843 to 0.850 and from 0.626 to 0.665, respectively.
      The reproducibility of maximum sTBF measurements obtained by methods was similar.
      CONCLUSIONS: In the evaluation of sTBF in gliomas, ASL with QUASAR at 3T yielded
      measurements and reproducibility similar to those of DSC perfusion MR imaging.

PMID- 21960504
TI  - Time trends and geographic variations in the prevalence of hypospadias in China.
AB  - BACKGROUND: Little is known about the main epidemiologic characteristics of
      hypospadias prevalence in China. We investigated the time trends and geographic
      variations in the prevalence of hypospadias in China from 1996 to 2008. METHODS:
      Data were retrieved from the hospital-based birth defects monitoring system in
      China from 1996 to 2008. We used prevalence ratios (PRs) to describe the
      difference in prevalence of hypospadias between urban and rural areas, as well as
      among different regions. Poisson regression was used to explore the long time
      trend for the prevalence of hypospadias and its regional disparity. RESULTS: The
      prevalences of hypospadias for isolated anomalies, multiple anomalies, and
      overall cases were 7.64, 1.39, and 9.03 per 10,000 births, respectively. The
      national PRs (urban vs. rural) of hypospadias for overall and isolated cases were
      1.25 (95% confidence interval [CI], 1.16-1.35) and 1.27 (95% CI, 1.17-1.38),
      respectively. The highest prevalence (12.10 per 10,000 births) was observed in
      the eastern region. A positive correlation was found between the prevalence of
      hypospadias and maternal age (p < 0.01). The average annual increase of 7.43%
      (95% CI, 5.52-9.38%) was observed in the overall prevalence of hypospadias in
      China; it was 5.28% (95% CI, 4.16-6.43%) in urban areas, 9.79% (95% CI, 7.72
      11.90%) in rural areas, 9.08% (95% CI, 6.36-11.86%) in the eastern region, 4.76%
      (95% CI, 2.93-6.62%) in the central region, and 6.57% (95% CI, 4.44-8.74%) in the
      western region. CONCLUSION: The increasing trends and differences of hypospadias
      prevalence by urban-rural classification and geographical location suggest that
      environmental exposure and maternal age might have a critical role in the
      development of hypospadias.

PMID- 21960505
TI  - The value of computed tomography scans in the diagnosis and management following
      invasive arterial investigation.
AB  - We report a patient who was known to have an abdominal aortic aneurysm and was
      being assessed for endovascular repair by calibrated angiogram, who developed
      back pain and cardiovascular collapse, where a computed tomography scan proved
      essential in establishing the correct diagnosis - bleed from an accessory renal
      artery branch.

PMID- 21960507
TI  - Occupational, environmental and lifestyle factors associated with spontaneous
      abortion.
AB  - Scientific evidence indicates extreme exposure sensitivity of embryos, fetuses,
      and infants to the persistent environmental/occupational chemicals directly and
      or indirectly as compared to the same magnitude of exposure in adults.
      Paternal/maternal exposure to some of these chemicals might have a effect on the
      gamete structure and function, which might have significant implication for the
      adverse effect on pregnancy and their outcome. The available data point that some
      of the organochlorine chemicals such as dichlorodiphenyl trichloroethane (DDT);
      metals such as lead, mercury; industrial pollutants such as dioxin, organic
      solvents, radiations; and some of the lifestyle-associated factors such as
      tobacco smoking (active and passive) and excessive maternal intake of alcohol had
      adverse effect on pregnancy outcome. The existing data support the hypothesis
      that, in general, working women have a higher risk of undesirable reproductive
      outcomes, even though the data are scanty. Studies are needed to find out the
      effects of those reproductive toxicants on priority basis which have been proved
      to be toxic in animal studies as well as data on human related to these chemicals
      are scanty. There is a need to educate the childbearing women to avoid exposure
      to the known or suspected risk factors and their employers to take measures to
      reduce the toxicant levels in workplace.

PMID- 21960508
TI  - Remission of endometriosis by hyperbaric oxygen treatment in rats.
AB  - We designed this prospective, randomized controlled animal study to determine the
      effects of hyperbaric oxygen (HBO) on experimentally induced endometriosis in a
      rat model. Surgical induction of endometriosis was performed in 40, nonpregnant,
      female, Wistar-Albino rats at the Experimental Medicine Research Center of
      Istanbul University (DETAE). Four weeks later, the first and second laparotomies
      for volume measurement and peritoneal fluid (PF) collection were performed, and
      the rats were divided randomly into the study and control groups. The study group
      was exposed to HBO treatment for 6 weeks. Then, a third laparotomy was performed
      on all of the rats. The volume, histopathologic scores, Ki-67 labeling of the
      endometriotic implants, and the levels of tumor necrosis factor-alpha (TNF-alpha)
      in the PF were measured. The mean volume of the endometriotic implants in the
      study group was significantly lower than that of the control group at the end of
      the study (57.4 +/- 12.5 vs 94.6 +/- 17.2 mm(3)). The mean histopathological
      scores (1.60 +/- 0.50 vs 2.42 +/- 0.51), Ki-67 immunohistochemical scores (1.50
      +/- 0.51 vs 2.37 +/- 0.49) of the endometriotic implants, and the TNF-alpha
      levels (5.33 +/- 1.02 vs 8.16 +/- 1.76 pg/mL) were significantly lower in the
      study group than in the control group. Hyperbaric oxygen treatment for 2 hours a
      day for 6 weeks resulted in significant remission of endometriosis in rats.

PMID- 21960510
TI  - Temporal changes in matrix metalloproteinases, their inhibitors, and cathepsins
      in mouse pubic symphysis during pregnancy and postpartum.
AB  - Remodeling and relaxation of the mouse pubic symphysis (PS) are central events in
      parturition. The involvement of endogenous proteins such as matrix
      metalloproteinases (MMPs), tissue inhibitors of matrix metalloproteinases
      (TIMPs), and cathepsins in these phenomena remains unclear. In this work, we used
      a combination of immunolocalization, protein expression/activity, and relative
      messenger RNA (mRNA) expression to examine the changes in selected MMPs (-2, -9,
      and -8), TIMPs (-1 and -2), and cathepsins (B and K) during pregnancy and
      postpartum in mice. Immunohistochemistry revealed the presence of all of these
      proteins in the cytoplasm of chondrocytes, fibrochondrocytes, and fibroblast-like
      cells in the interpubic tissues. Zymography showed increases in the active forms
      of MMP-2 and -9 primarily on days 15 to 19 of pregnancy. Western blotting showed
      enhanced expression of MMP-8 on days 12 to 15 of pregnancy, with no changes in
      cathepsins B and K. Matrix metalloproteinases 2, TIMP-1 and -2, and cathepsin B
      had significant relative gene expression throughout pregnancy. These findings
      indicate that during pregnancy and postpartum there are variations in the
      expression and activity of proteins that may have an important role in remodeling
      the pubic symphysis during these events.

PMID- 21960509
TI  - Long-term maternal hypoxia: the role of extracellular Ca2+ entry during serotonin
      mediated contractility in fetal ovine pulmonary arteries.
AB  - Antenatal maternal long-term hypoxia (LTH) can alter serotonin (5-HT) and calcium
      (Ca(2+)) signaling in fetal pulmonary arteries (PAs) and is associated with
      persistent pulmonary hypertension of the newborn (PPHN). In humans, the antenatal
      maternal hypoxia can be secondary to smoking, anemia, and chronic obstructive
      pulmonary disorders. However, the mechanisms of antenatal maternal hypoxia
      related PPHN are unresolved. Because both LTH and 5-HT are associated with PPHN,
      we tested the hypothesis that antenatal maternal LTH can increase 5-HT-mediated
      PA contraction and associated extracellular Ca(2+) influx through L-type Ca(2+)
      channels (Ca(L)), nonselective cation channels (NSCCs), and reverse-mode sodium
      calcium exchanger (NCX) in the near-term fetus. We performed wire myography and
      confocal-Ca(2+) imaging approaches on fetal lamb PA (~ 140 days of gestation)
      from normoxic ewes or those acclimatized to high-altitude LTH (3801 m) for ~110
      days. Long-term hypoxia reduced the potency but not the efficacy of 5-HT-induced
      PA contraction. Ketanserin (100 nmol/L), a 5-HT(2A) antagonist, shifted 5-HT
      potency irrespective of LTH, while GR-55562 (1 umol/L), a 5-HT(1B/D) inhibitor,
      antagonized 5-HT-induced contraction in normoxic fetuses only. Various inhibitors
      for Ca(L), NSCC, and reverse-mode NCX were used in contraction studies.
      Contraction was reliant on extracellular Ca(2+) regardless of maternal hypoxia,
      NSCC was more important to contraction than Ca(L), and reverse-mode NCX had
      little or no role in contraction. Long-term hypoxia also attenuated the effects
      of 2-APB and flufenamic acid and reduced Ca(2+) responses observed by imaging
      studies. Overall, LTH reduced 5HT(1B/D) function and increased NSCC-related
      Ca(2+)-dependent contraction in ovine fetuses, which may compromise pulmonary
      vascular function in the newborn.

PMID- 21960511
TI  - The effect of intermittent umbilical cord occlusion on elastin composition in the
      ovine fetus.
AB  - This study aimed to determine the effect of varying degrees of intermittent
      umbilical cord occlusion (UCO) on arterial elastin composition. Over 4 days,
      chronically catheterized late gestation fetal sheep received 5 total UCO per day
      lasting 1 min/h (mild group: n = 6), 2 min/h (moderate group: n = 4), 3 min/h
      (severe group; n = 6); or no occlusion (control group: n = 7). Each group was
      evaluated for elastin content of the carotid and superior mesenteric artery
      (SMA), the arterial pressure response to UCO, and plasma cortisol concentration.
      Elastin content of the carotid artery was significantly increased by severe UCO
      (9.5 ug/mg versus 6.4 ug/mg; P < .05) and insignificantly increased in mild and
      moderate groups, whereas UCO had no effect on elastin content of the SMA. This
      dose- and site-dependent response of the vasculature appears attributable to the
      hemodynamic changes that accompany UCO.

PMID- 21960512
TI  - Early-pregnancy changes in maternal lipid profile in women with recurrent
      preeclampsia and previously preeclamptic women with normal next pregnancy.
AB  - OBJECTIVE: To evaluate early-pregnancy changes in lipid profile in recurrent
      preeclampsia. METHODS: In this retrospective observational study, blood samples
      were obtained from 41 normotensive women with a history of early-onset
      preeclampsia preconceptionally and at 12 and 16 weeks in the next pregnancy. We
      assessed triglycerides (TGs), total cholesterol (TC), and high- and low-density
      lipoprotein cholesterol (HDL-C and LDL-C, respectively). We analyzed differences
      in longitudinal patterns between normal and recurrent preeclamptic next pregnancy
      using mixed-design repeated measurements analysis of covariance (ANCOVA).
      RESULTS: Eleven (28%) women developed recurrent preeclampsia. Eighteen (45%)
      women had a normal pregnancy. In normal pregnancy, LDL-C declines transiently in
      the first trimester (P < .01). In women who develop recurrent preeclampsia later
      on this decline was absent. Moreover, from 12 weeks onward the elevating levels
      of HDL-C stagnates in women who subsequently develop recurrent preeclampsia (P =
      .02). CONCLUSION: These observations point to an abnormal early adaptation of
      lipid metabolism to pregnancy preceding clinical manifestation of preeclampsia.

PMID- 21960513
TI  - Clinical significance of sperm DNA damage threshold value in the assessment of
      male infertility.
AB  - Sperm DNA integrity is a prerequisite for normal spermatozoal function. The aim
      of the study was to evaluate the role of sperm chromatin damage, its cut-off
      level and its effect on sperm parameters in men with idiopathic infertility by
      analyzing 100 idiopathic infertile men and 50 fertile controls. Semen samples
      were analyzed as per WHO 1999 guidelines and sperm chromatin structure assay
      (SCSA) was applied to measure DNA fragmentation index (DFI) in sperm. The mean
      DFI of infertile men (35.75) was significantly (P < .0001) higher as compared to
      controls (26.22). The threshold level of 30.28% was obtained as cut-off value to
      discriminate infertile men from fertile controls. Sperm count, forward motility,
      and normal morphology found to be negatively associated with DFI in overall study
      subjects. Infertile men with severe oligozoospermia had higher mean DFI (40.01 +/
      11.31) than infertile men with oligozoospermia (35.11 +/- 10.05) and normal
      sperm count (33.99 +/- 9.96). Moreover 64% of infertile men have DFI > 30 against
      6% of fertile controls (P < .0001). Higher sperm DNA fragmentation may be the
      underlying cause for poor semen quality in idiopathic infertile men and the
      threshold value of 30.28% is a clear discriminator to distinguish infertile men
      from fertile men of Indian population. Thus, DFI is a good prognostic marker as
      cases with higher sperm DFI may have poor success rate even after assisted
      conception and may experience recurrent pregnancy loss (RPL) and should be
      counseled accordingly.

PMID- 21960514
TI  - Use of active surveillance methodologies to examine over-reporting of stillbirths
      on fetal death certificates.
AB  - BACKGROUND: Data from Iowa fetal death certificates (FDCs) suggest that
      reportable stillbirths (unintended fetal deaths >= 20 weeks gestation and/or
      weighing >= 350 grams) occur in about 1 in 200 deliveries. In 2005, the Iowa
      Department of Public Health and the Iowa Registry for Congenital and Inherited
      Disorders (IRCID) collaborated with other state stakeholders to establish the
      Iowa Stillbirth Surveillance Project. The goal of this project was to use
      population-based, active surveillance methodologies to identify reportable
      stillbirths delivered by Iowa residents since January 1, 2000. METHODS: To
      conduct stillbirth surveillance, the IRCID expanded its existing public health
      authority and electronic abstract application for birth defects surveillance. The
      expanded application was piloted using a random sample (n = 250 of 989) of FDCs
      reported from January 2000 through December 2004. RESULTS: IRCID procedures for
      active case finding and medical record abstraction verified 192 (76.8%) as
      reportable stillbirths. Stillbirths not verified as reportable were due to
      findings of elective terminations (n = 30), live births (n = 3), induced
      deliveries (n = 2), and FDC entries for gestational age and/or delivery weight
      that were either inaccurately recorded (n = 13) or accurately recorded but did
      not meet Iowa FDC reporting criteria (n = 9); medical records for one FDC were
      unavailable. Infant malformations were more common among unverified stillbirths,
      whereas the cause of death due to maternal-related conditions was higher among
      verified stillbirths. CONCLUSIONS: These results suggest that over-reporting
      limits the use of FDCs as a primary ascertainment source for stillbirth
      surveillance in Iowa. Continued expansion of the IRCID active surveillance
      methodologies to monitor stillbirths in Iowa is recommended.

PMID- 21960515
TI  - Twenty-five-year survival of children with birth defects in New York State: a
      population-based study.
AB  - BACKGROUND: Few studies have been conducted on long-term survival of children
      with major birth defects because of a lack of longitudinal birth defects
      surveillance data. The objective of this study was to conduct a 25-year survival
      analysis among children in New York born with major defects by survival age,
      birth defect category, and other possible contributing factors. METHODS: A cohort
      was constructed containing children born in 1983 to 2006 with selected major
      birth defects. Deaths among the study cohort were identified by matching the
      children to their death certificates. The survival probability was estimated by
      Kaplan-Meier methods. Cox proportional hazards regression was used to examine the
      effect of the risk factors on survival. RESULTS: A total of 9112 deaths were
      identified among 57,002 live births with selected birth defects between 1983 and
      2006. The overall 25-year survival probability of the study cohort was 82.51%
      (95% confidence interval, 82.11-82.89%). The estimated survival probability was
      comparable to that reported from previous studies regarding individual defects
      including spina bifida, encephalocele, atrioventricular septal defects,
      tracheoesophageal fistula and esophageal atresia or stenosis, renal agenesis or
      dysgenesis, lower limb reduction, diaphragmatic hernia, abdominal wall defects,
      and Down syndrome. Sex, low birth weight for gestational age, existence of
      multiple birth defects (nonisolated), and maternal age and nativity were
      identified as risk factors. CONCLUSION: Using the statewide, population-based
      birth defects surveillance data in New York State, the survival experience of the
      study cohort was examined across all survival time periods by individual birth
      defect of interest. Several risk factors that affect survival were identified.

PMID- 21960516
TI  - Adolescents who have sexually offended: is phallometry valid?
AB  - It is unclear whether deviant sexual preferences distinguish adolescents who
      commit sex offenses in the same way that such deviance characterizes adult sex
      offenders. We compared male adolescents (mean age = 15 at the time of a referral
      sex offense), matched adult sex offenders, and normal men (adult nonoffenders or
      nonsex offenders). We hypothesized the following: phallometric responses of the
      adolescents would be similar to those of adult sex offenders and would differ
      from normals; adolescents with male child victims would exhibit greater evidence
      of sexual deviance than those whose only victims were female children; among
      adolescents who had molested children, those with a history of sexual abuse would
      exhibit more evidence of sexual deviance than those with no such history; and
      phallometric measures would predict recidivism. With some notable exceptions or
      qualifications, results confirmed the hypotheses. Phallometry has valid clinical
      and research uses with adolescent males who commit serious sex offenses.

PMID- 21960517
TI  - Correlates of recidivism among adolescents who have sexually offended.
AB  - The present study investigates the recidivism rates of a sample of 351 male
      adolescents who sexually offended, and were assessed at an outpatient psychiatric
      clinic in Montreal, Canada, between 1992 and 2002. The mean age of the
      participants was 15.8 years (SD=1.8). Data on adolescent and adult recidivism
      were collected in Summer 2005 from official criminality sources in Canada. Over
      an 8-year follow-up period, 45% (n=158) of the participants were charged with a
      new criminal offense, 30% (n=104) were charged with a violent offense, and 10%
      (n=36) were charged with a sexual offense. Cox regression results suggest that
      overall, violent, and sexual recidivism can be predicted by a variety of
      developmental, social, and criminological factors. Paternal abandonment,
      childhood sexual victimization, association with significantly younger children,
      and having victimized a stranger were associated with a higher risk of sexual
      recidivism. Previous delinquency, attention deficit disorder, and childhood
      sexual victimization were found to increase the risk for both violent and overall
      recidivism. Also, the use of violence during a sex crime and victimizing a
      stranger were associated with violent recidivism, and school delay and
      association with delinquent peers were predictive of overall recidivism. The
      results confirm that a significant proportion of adolescents who have sexually
      offended pursue a criminal activity beyond adolescence, although few specialize
      in sexual offending.

PMID- 21960518
TI  - Phenotype evaluation and genomewide linkage study of clinical variables in
      schizophrenia.
AB  - Genetic factors are likely to influence clinical variation in schizophrenia, but
      it is unclear which variables are most suitable as phenotypes and which molecular
      genetic loci are involved. We evaluated clinical variable phenotypes and applied
      suitable phenotypes in genome-wide covariate linkage analysis. We ascertained 170
      affected relative pairs (168 sibling-pairs and two avuncular pairs) with DSM-IV
      schizophrenia or schizoaffective disorder from the United Kingdom. We defined
      psychotic symptom dimensions, age at onset (AAO), and illness course using the
      OPCRIT checklist. We evaluated phenotypes using within sibling-pair correlations
      and applied suitable phenotypes in multipoint covariate linkage analysis based on
      372 microsatellite markers at ~10 cM intervals. The statistical significance of
      linkage results was assessed by simulation. The positive and disorganized symptom
      dimensions, AAO, and illness course qualified as suitable phenotypes. There were
      no genome-wide significant linkage results. There was suggestive evidence of
      linkage for the positive dimension on chromosomes 2q32, 10q26, and 20q12; the
      disorganized dimension on 8p21 and 17q21; and illness course on 2q33 and 22q11.
      The linkage peak for disorganization on 17q21 remained suggestive after
      correction for multiple testing. To our knowledge, this is the first study to
      integrate phenotype evaluation and genome-wide covariate linkage analysis for
      symptom dimensions and illness history variables in sibling-pairs with
      schizophrenia. The significant within-pair correlations strengthen the evidence
      that some clinical variables within schizophrenia are suitable phenotypes for
      molecular genetic investigations. At present there are no genome-wide significant
      linkage results for these phenotypes, but a number of suggestive findings warrant
      further investigation.

PMID- 21960519
TI  - Characterization of motor patterns in isolated human colon: are there differences
      in patients with slow-transit constipation?
AB  - The patterns of motor activity that exist in isolated full-length human colon
      have not been described. Our aim was to characterize the spontaneous motor
      patterns in isolated human colon and determine whether these patterns are
      different in whole colons obtained from patients with slow-transit constipation
      (STC). The entire colon (excluding the anus), was removed from patients with
      confirmed STC and mounted longitudinally in an organ bath ~120 cm in length,
      containing oxygenated Krebs' solution at 36 degrees C. Changes in circular muscle
      tension were recorded from multiple sites simultaneously along the length of
      colon, by use of isometric force transducers. Recordings from isolated colons
      from non-STC patients revealed cyclical colonic motor complexes (CMCs) in 11 of
      17 colons, with a mean interval and half-duration of contractions of 4.0 +/- 0.6
      min and 51.5 +/- 15 s, respectively. In the remaining six colons, spontaneous
      irregular phasic contractions occurred without CMCs. Interestingly, in STC
      patients robust CMCs were still recorded, although their CMC pacemaker
      frequencies were slower. Intraluminal balloon distension of the ascending or
      descending colon evoked an ascending excitatory reflex contraction, or evoked
      CMC, in 8 of 30 trials from non-STC (control) colons, but not from colons
      obtained from STC patients. In many control segments of descending colon,
      spontaneous CMCs consisted of simultaneous ascending excitatory and descending
      inhibitory phases. In summary, CMCs can be recorded from isolated human colon, in
      vitro, but their intrinsic pacemaker frequency is considerably faster in vitro
      compared with previous human recordings of CMCs in vivo. The observation that
      CMCs occur in whole colons removed from STC patients suggests that the intrinsic
      pacemaker mechanisms underlying their generation and propagation are preserved in
      vitro, despite impaired transit along these same regions in vivo.

PMID- 21960520
TI  - Effect of synthetic cationic protein on mechanoexcitability of vagal afferent
      nerve subtypes in guinea pig esophagus.
AB  - Eosinophilic esophagitis is characterized by increased infiltration and
      degranulation of eosinophils in the esophagus. Whether eosinophil-derived
      cationic proteins regulate esophageal sensory nerve function is still unknown.
      Using synthetic cationic protein to investigate such effect, we performed
      extracellular recordings from vagal nodose or jugular neurons in ex vivo
      esophageal-vagal preparations with intact nerve endings in the esophagus. Nerve
      excitabilities were determined by comparing action potentials evoked by
      esophageal distensions before and after perfusion of synthetic cationic protein
      poly-L-lysine (PLL) with or without pretreatment with poly-L-glutamic acid
      (PLGA), which neutralized cationic charges of PLL. Perfusion with PLL did not
      evoke action potentials in esophageal nodose C fibers but increased their
      responses to esophageal distension. This potentiation effect lasted for 30 min
      after washing out of PLL. Pretreatment with PLGA significantly inhibited PLL
      induced mechanohyperexcitability of esophageal nodose C fibers. In esophageal
      nodose Adelta fibers, perfusion with PLL did not evoke action potentials. In
      contrast to nodose C fibers, both the spontaneous discharges and the responses to
      esophageal distension in nodose Adelta fibers were decreased by perfusion with
      PLL, which can be restored after washing out PLL for 30-60 min. Pretreatment with
      PLGA attenuated PLL-induced decrease in spontaneous discharge and
      mechanoexcitability of esophageal nodose Adelta fibers. In esophageal jugular C
      fibers, PLL neither evoked action potentials nor changed their responses to
      esophageal distension. Collectively, these data demonstrated that synthetic
      cationic protein did not evoke action potential discharges of esophageal vagal
      afferents but had distinctive sensitization effects on their responses to
      esophageal distension.

PMID- 21960522
TI  - Establishment of tolerance to commensal bacteria requires a complex microbiota
      and is accompanied by decreased intestinal chemokine expression.
AB  - Intricate regulation of tolerance to the intestinal commensal microbiota acquired
      at birth is critical. We hypothesized that epithelial cell tolerance toward early
      gram-positive and gram-negative colonizing bacteria is established immediately
      after birth, as has previously been shown for endotoxin. Gene expression in the
      intestine of mouse pups born to dams that were either colonized with a
      conventional microbiota or monocolonized (Lactobacillus acidophilus or Eschericia
      coli) or germ free was examined on day 1 and day 6 after birth. Intestinal
      epithelial cells from all groups of pups were stimulated ex vivo with L.
      acidophilus and E. coli to assess tolerance establishment. Intestine from pups
      exposed to a conventional microbiota displayed lower expression of Ccl2, Ccl3,
      Cxcl1, Cxcl2, and Tslp than germ-free mice, whereas genes encoding proteins in
      Toll-like receptor signaling pathways and cytokines were upregulated. When
      comparing pups on day 1 and day 6 after birth, a specific change in gene
      expression pattern was evident in all groups of mice. Tolerance to ex vivo
      stimulation with E. coli was only established in conventional animals.
      Colonization of the intestine was reflected in the spleen displaying
      downregulation of Cxcl2 compared with germ-free animals on day 1 after birth.
      Colonization reduced the expression of genes involved in antigen presentation in
      the intestine-draining mesenteric lymph nodes, but not in the popliteal lymph
      nodes, as evidenced by gene expression on day 23 after birth. We propose that
      microbial detection systems in the intestine are upregulated by colonization with
      a diverse microbiota, whereas expression of proinflammatory chemokines is reduced
      to avoid excess recruitment of immune cells to the maturing intestine.

PMID- 21960521
TI  - ATP: a mediator for HCl-induced TRPV1 activation in esophageal mucosa.
AB  - In esophageal mucosa, HCl causes TRPV1-mediated release of calcitonin gene
      related peptide (CGRP) and substance P (SP) from submucosal neurons and of
      platelet-activating factor (PAF) from epithelial cells. CGRP and SP release was
      unaffected by PAF antagonists but reduced by the purinergic antagonist suramin.
      ATP caused CGRP and SP release from esophageal mucosa, confirming a role of ATP
      in the release. The human esophageal epithelial cell line HET-1A was used to
      identify epithelial cells as the site of ATP release. HCl caused ATP release from
      HET-1A, which was reduced by the TRPV1 antagonist 5-iodoresiniferatoxin. Real
      time PCR demonstrated the presence of mRNA for several P2X and P2Y purinergic
      receptors in epithelial cells. HCl also increased activity of lyso-PAF acetyl-CoA
      transferase (lyso-PAF AT), the enzyme responsible for production of PAF. The
      increase was blocked by suramin. ATP caused a similar increase, confirming ATP as
      a mediator for the TRPV1-induced increase in enzyme activity. Repeated exposure
      of HET-1A cells to HCl over 2 days caused upregulation of mRNA and protein
      expression for lyso-PAF AT. Suramin blocked this response. Repeated exposure to
      ATP caused a similar mRNA increase, confirming ATP as a mediator for upregulation
      of the enzyme. Thus, HCl-induced activation of TRPV1 causes ATP release from
      esophageal epithelial cells that causes release of CGRP and SP from esophageal
      submucosal neurons and activation of lyso-PAF AT, the enzyme responsible for the
      production of PAF in epithelial cells. Repeated application of HCl or of ATP
      causes upregulation of lyso-PAF AT in epithelial cells.

PMID- 21960523
TI  - Regulation of Ca2+ release through inositol 1,4,5-trisphosphate receptors by
      adenine nucleotides in parotid acinar cells.
AB  - Secretagogue-stimulated intracellular Ca(2+) signals are fundamentally important
      for initiating the secretion of the fluid and ion component of saliva from
      parotid acinar cells. The Ca(2+) signals have characteristic spatial and temporal
      characteristics, which are defined by the specific properties of Ca(2+) release
      mediated by inositol 1,4,5-trisphosphate receptors (InsP(3)R). In this study we
      have investigated the role of adenine nucleotides in modulating Ca(2+) release in
      mouse parotid acinar cells. In permeabilized cells, the Ca(2+) release rate
      induced by submaximal [InsP(3)] was increased by 5 mM ATP. Enhanced Ca(2+)
      release was not observed at saturating [InsP(3)]. The EC(50) for the augmented
      Ca(2+) release was ~8 MUM ATP. The effect was mimicked by nonhydrolysable ATP
      analogs. ADP and AMP also potentiated Ca(2+) release but were less potent than
      ATP. In acini isolated from InsP(3)R-2-null transgenic animals, the rate of
      Ca(2+) release was decreased under all conditions but now enhanced by ATP at all
      [InsP(3)]. In addition the EC(50) for ATP potentiation increased to ~500 MUM.
      These characteristics are consistent with the properties of the InsP(3)R-2
      dominating the overall features of InsP(3)R-induced Ca(2+) release despite the
      expression of all isoforms. Finally, Ca(2+) signals were measured in intact
      parotid lobules by multiphoton microscopy. Consistent with the release data,
      carbachol-stimulated Ca(2+) signals were reduced in lobules exposed to
      experimental hypoxia compared with control lobules only at submaximal
      concentrations. Adenine nucleotide modulation of InsP(3)R in parotid acinar cells
      likely contributes to the properties of Ca(2+) signals in physiological and
      pathological conditions.

PMID- 21960524
TI  - "They're going to unplug grandma": advance directive discussions and
      documentation do not decrease survival in patients at baseline lower risk of
      death.
AB  - OBJECTIVE: To determine the effect of having advance directive (AD) discussions
      or having an AD in the medical record on patient survival. DESIGN: Prospective
      observational cohort study. SETTING: Three Colorado area hospitals: a large
      academic tertiary referral center, a Veteran's Affairs medical center, and an
      urban safety net hospital. PARTICIPANTS: Four hundred fifty-eight adults admitted
      to the general internal medicine service interviewed about AD discussions. A
      concurrent chart review documented the presence of an AD in the medical record.
      Participants were stratified into low, medium, and high risk of death within 1
      year based on validated prognostic criteria. MEASURES: Kaplan-Meier survival
      plots were estimated for those at low and medium risk of death. RESULTS: No
      significant differences in survival for participants at low and medium risk of
      death who reported having had an AD discussion and those who had not (Wilcoxon
      low risk, P = 0.97; medium risk, P = 0.28; and log-rank low risk, P = 0.82;
      medium risk, P = 0.45), and for those who had an AD in the medical record vs
      those who did not (Wilcoxon low risk, P = 0.84; medium risk, P = 0.78; and log
      rank low risk, P = 0.86; medium risk, P = 0.69). CONCLUSIONS: There is no
      evidence that AD discussions or documentation result in increased mortality. In
      regards to the current national debate about the merits of advance care planning,
      this study suggests that honoring patients' wishes to engage in AD discussions
      and documentation does not lead to harm.

PMID- 21960525
TI  - Wrinkled liquid-crystalline microparticle-enhanced photoresponse of PDLC-like
      films by coupling with mechanical stretching.
AB  - Photoresponsive behaviors are studied in hybrid liquid-crystalline (LC) films
      prepared with light-responsive LC polymer microparticles as dopants using
      photoinert polymers as a host material. Upon mechanical stretching, both
      topological shape change and mesogenic alignment occur in the LC polymer
      microparticles, enabling the polymer-dispersed LC (PDLC)-like films to bend
      toward a light source upon UV irradiation. The rough morphologies of the
      hydrophobic LC microparticles enhance their interactions with hydrophilic polymer
      substrates. The bilayer-like structures of the hybrid film formed in the
      fabrication processes are responsible for the photomechanical behavior, which is
      reversibly controlled by combing light irradiation with the stretching processes.

PMID- 21960526
TI  - Therapeutic targeting of Myc-reprogrammed cancer cell metabolism.
AB  - Studies from many laboratories document that the MYC oncogene produces a
      pleiotropic transcription factor, Myc, which influences genes driven by all three
      RNA polymerases to orchestrate nutrient import with biomass accumulation for cell
      division. Myc has been shown to activate genes involved in glycolysis,
      glutaminolysis, and mitochondrial biogenesis to provide ATP and anabolic
      substrates for cell mass accumulation. Myc stimulates ribosome biogenesis and
      orchestrates the energetic demand for biomass accumulation through its regulation
      of glucose and glutamine import and metabolism. When normal cells are deprived of
      nutrients, endogenous MYC expression diminishes and cells withdraw from the cell
      cycle. However, ectopic MYC-driven cancer cells are locked in a state of
      deregulated biomass accumulation, which renders them addicted to glucose and
      glutamine. This addictive state can be exploited for cancer therapy, because
      nutrient deprivation kills Myc-driven cells and inhibition of the Myc targets,
      lactate dehydrogenase A or glutaminase, diminishes tumor xenograft growth in
      vivo.

PMID- 21960527
TI  - Skeletal muscle stem cells: effects of aging and metabolism on muscle
      regenerative function.
AB  - Homeostatic and regenerative replacement of skeletal muscle fibers requires the
      activity of a dedicated pool of myogenic stem cells, called satellite cells, that
      are activated by muscle injury and act as a renewable source of muscle-forming
      cells throughout adult life. Satellite cell function is controlled by both
      intrinsic and extrinsic regulatory cues, whose integration determines the success
      of muscle regenerative responses. Pathological deregulation of satellite cell
      function through perturbation of these signaling pathways appears to play an
      important role in age-dependent deterioration of muscle function and in muscle
      dystrophic disease. The regenerative activity of skeletal muscle also appears to
      be tightly linked to metabolism, and alterations in metabolic state can directly
      influence the activity of these tissue-specific stem cells. Here, we review
      recent and emerging insights into the molecular and biochemical signals that
      control satellite cell function and discuss these in the context of muscle
      degenerative diseases such as dystrophy and sarcopenia. Novel discoveries from
      this ongoing work bring new opportunities to enhance or restore muscle repair and
      are likely to facilitate satellite cell transplantation in clinical applications.

PMID- 21960528
TI  - Wireless solar water splitting using silicon-based semiconductors and earth
      abundant catalysts.
AB  - We describe the development of solar water-splitting cells comprising earth
      abundant elements that operate in near-neutral pH conditions, both with and
      without connecting wires. The cells consist of a triple junction, amorphous
      silicon photovoltaic interfaced to hydrogen- and oxygen-evolving catalysts made
      from an alloy of earth-abundant metals and a cobalt|borate catalyst,
      respectively. The devices described here carry out the solar-driven water
      splitting reaction at efficiencies of 4.7% for a wired configuration and 2.5% for
      a wireless configuration when illuminated with 1 sun (100 milliwatts per square
      centimeter) of air mass 1.5 simulated sunlight. Fuel-forming catalysts interfaced
      with light-harvesting semiconductors afford a pathway to direct solar-to-fuels
      conversion that captures many of the basic functional elements of a leaf.

PMID- 21960529
TI  - Anthropogenic aerosols and the weakening of the South Asian summer monsoon.
AB  - Observations show that South Asia underwent a widespread summertime drying during
      the second half of the 20th century, but it is unclear whether this trend was due
      to natural variations or human activities. We used a series of climate model
      experiments to investigate the South Asian monsoon response to natural and
      anthropogenic forcings. We find that the observed precipitation decrease can be
      attributed mainly to human-influenced aerosol emissions. The drying is a robust
      outcome of a slowdown of the tropical meridional overturning circulation, which
      compensates for the aerosol-induced energy imbalance between the Northern and
      Southern Hemispheres. These results provide compelling evidence of the prominent
      role of aerosols in shaping regional climate change over South Asia.

PMID- 21960530
TI  - Late interleukin-6 escalates T follicular helper cell responses and controls a
      chronic viral infection.
AB  - Multiple inhibitory molecules create a profoundly immunuosuppressive environment
      during chronic viral infections in humans and mice. Therefore, eliciting
      effective immunity in this context represents a challenge. Here, we report that
      during a murine chronic viral infection, interleukin-6 (IL-6) was produced by
      irradiation-resistant cells in a biphasic manner, with late IL-6 being absolutely
      essential for viral control. The underlying mechanism involved IL-6 signaling on
      virus-specific CD4 T cells that caused up-regulation of the transcription factor
      Bcl6 and enhanced T follicular helper cell responses at late, but not early,
      stages of chronic viral infection. This resulted in escalation of germinal center
      reactions and improved antibody responses. Our results uncover an antiviral
      strategy that helps to safely resolve a persistent infection in vivo.

PMID- 21960531
TI  - Bidirectional control of social hierarchy by synaptic efficacy in medial
      prefrontal cortex.
AB  - Dominance hierarchy has a profound impact on animals' survival, health, and
      reproductive success, but its neural circuit mechanism is virtually unknown. We
      found that dominance ranking in mice is transitive, relatively stable, and highly
      correlates among multiple behavior measures. Recording from layer V pyramidal
      neurons of the medial prefrontal cortex (mPFC) showed higher strength of
      excitatory synaptic inputs in mice with higher ranking, as compared with their
      subordinate cage mates. Furthermore, molecular manipulations that resulted in an
      increase and decrease in the synaptic efficacy in dorsal mPFC neurons caused an
      upward and downward movement in the social rank, respectively. These results
      provide direct evidence for mPFC's involvement in social hierarchy and suggest
      that social rank is plastic and can be tuned by altering synaptic strength in
      mPFC pyramidal cells.

PMID- 21960532
TI  - Ionic liquid-mediated selective conversion of CO2 to CO at low overpotentials.
AB  - Electroreduction of carbon dioxide (CO(2))--a key component of artificial
      photosynthesis--has largely been stymied by the impractically high overpotentials
      necessary to drive the process. We report an electrocatalytic system that reduces
      CO(2) to carbon monoxide (CO) at overpotentials below 0.2 volt. The system relies
      on an ionic liquid electrolyte to lower the energy of the (CO(2))(-)
      intermediate, most likely by complexation, and thereby lower the initial
      reduction barrier. The silver cathode then catalyzes formation of the final
      products. Formation of gaseous CO is first observed at an applied voltage of 1.5
      volts, just slightly above the minimum (i.e., equilibrium) voltage of 1.33 volts.
      The system continued producing CO for at least 7 hours at Faradaic efficiencies
      greater than 96%.

PMID- 21960534
TI  - Evidence for a causal relationship between allergic sensitization and rhinovirus
      wheezing in early life.
AB  - RATIONALE: Aeroallergen sensitization and virus-induced wheezing are risk factors
      for asthma development during early childhood, but the temporal developmental
      sequence between them is incompletely understood. OBJECTIVE: To define the
      developmental relationship between aeroallergen sensitization and virus-induced
      wheezing. METHODS: A total of 285 children at high risk for allergic disease and
      asthma were followed prospectively from birth. The timing and etiology of viral
      respiratory wheezing illnesses were determined, and aeroallergen sensitization
      was assessed annually for the first 6 years of life. The relationships between
      these events were assessed using a longitudinal multistate Markov model.
      MEASUREMENTS AND MAIN RESULTS: Children who were sensitized to aeroallergens had
      greater risk of developing viral wheeze than nonsensitized children (hazard ratio
      [HR], 1.9; 95% confidence interval [CI], 1.2-3.1). Allergic sensitization led to
      an increased risk of wheezing illnesses caused by human rhinovirus (HRV) but not
      respiratory syncytial virus. The absolute risk of sensitized children developing
      viral wheeze was greatest at 1 year of age; however, the relative risk was
      consistently increased at every age assessed. In contrast, viral wheeze did not
      lead to increased risk of subsequent allergic sensitization (HR, 0.76; 95% CI,
      0.50-1.1). CONCLUSIONS: Prospective, repeated characterization of a birth cohort
      demonstrated that allergic sensitization precedes HRV wheezing and that the
      converse is not true. This sequential relationship and the plausible mechanisms
      by which allergic sensitization can lead to more severe HRV-induced lower
      respiratory illnesses support a causal role for allergic sensitization in this
      developmental pathway. Therefore, therapeutics aimed at preventing allergic
      sensitization may modify virus-induced wheezing and the development of asthma.

PMID- 21960535
TI  - The calcium sensitizer levosimendan improves human diaphragm function.
AB  - RATIONALE: Acquired diaphragm muscle weakness is a key feature in several chronic
      conditions, including chronic obstructive pulmonary disease, congestive heart
      failure, and difficult weaning from mechanical ventilation. No drugs are
      available to improve respiratory muscle function in these patients. Recently, we
      have shown that the calcium sensitizer levosimendan enhances the force-generating
      capacity of isolated diaphragm fibers. OBJECTIVES: To investigate the effects of
      the calcium sensitizer levosimendan on in vivo human diaphragm function. METHODS:
      In a double-blind, randomized, crossover design, 30 healthy subjects performed
      two identical inspiratory loading tasks. After the first loading task, subjects
      received levosimendan (40 MUg/kg bolus followed by 0.1/0.2 MUg/kg/min continuous
      infusion) or placebo. Transdiaphragmatic pressure, diaphragm electrical activity,
      and their relationship (neuromechanical efficiency) were measured during loading.
      Magnetic phrenic nerve stimulation was performed before the first loading task
      and after bolus administration to assess twitch contractility. Center frequency
      of diaphragm electrical activity was evaluated to study the effects of
      levosimendan on muscle fiber conduction velocity. MEASUREMENTS AND MAIN RESULTS:
      The placebo group showed a 9% (P=0.01) loss of twitch contractility after loaded
      breathing, whereas no loss in contractility was observed in the levosimendan
      group. Neuro-mechanical efficiency of the diaphragm during loading improved by
      21% (P<0.05) in the levosimendan group. Baseline center frequency of diaphragm
      electrical activity was reduced after levosimendan administration (P<0.05).
      CONCLUSIONS: The calcium sensitizer levosimendan improves neuromechanical
      efficiency and contractile function of the human diaphragm. Our findings suggest
      a new therapeutic approach to improve respiratory muscle function in patients
      with respiratory failure.

PMID- 21960537
TI  - Special issue on illicit drugs.

PMID- 21960536
TI  - A review of alpha1-antitrypsin deficiency.
AB  - alpha(1)-Antitrypsin (AAT) deficiency is an underrecognized genetic condition
      that affects approximately 1 in 2,000 to 1 in 5,000 individuals and predisposes
      to liver disease and early-onset emphysema. AAT is mainly produced in the liver
      and functions to protect the lung against proteolytic damage (e.g., from
      neutrophil elastase). Among the approximately 120 variant alleles described to
      date, the Z allele is most commonly responsible for severe deficiency and
      disease. Z-type AAT molecules polymerize within the hepatocyte, precluding
      secretion into the blood and causing low serum AAT levels (~ 3-7 MUM with normal
      serum levels of 20-53 MUM). A serum AAT level of 11 MUM represents the protective
      threshold value below which the risk of emphysema is believed to increase. In
      addition to the usual treatments for emphysema, infusion of purified AAT from
      pooled human plasma-so-called "augmentation therapy"-represents a specific
      therapy for AAT deficiency and raises serum levels above the protective
      threshold. Although definitive evidence from randomized controlled trials of
      augmentation therapy is lacking and therapy is expensive, the available evidence
      suggests that this approach is safe and can slow the decline of lung function and
      emphysema progression. Promising novel therapies are under active investigation.

PMID- 21960538
TI  - Doors of deception: the diaspora of designer drugs.

PMID- 21960539
TI  - Detection of drugs of abuse by Raman spectroscopy.
AB  - Raman spectroscopy can provide rapid, sensitive, non-destructive analysis of a
      variety of drug types (e.g. amphetamines, alkaloids, designer drugs, and date
      rape drugs). This review concentrates on developments in the past 15 years. It
      considers identification and quantification of drugs of abuse in different types
      of forensic evidence, including bulk street drugs as well as traces found in
      drinks, on fibres/clothing, in fingerprints, on fingernails, on bank notes, and
      in body fluids.

PMID- 21960540
TI  - GHB and synthetic cathinones: clinical effects and potential consequences.
AB  - Designer drugs belong to a group of legally or illegally produced substances that
      are structurally and pharmacologically very similar to illicit drugs. In the
      past, designer drugs were often used during all-night dance parties, but they are
      now consumed in multiple settings from college bars to parks to private house
      parties. Most of these club drugs can be bought on legal websites and home
      delivered for private parties. Recently, legal highs have once again become a
      burning media issue across the world. Our review will focus on GHB and synthetic
      cathinones. Literature searches were conducted for the period from 1975 to July
      2010 using PubMed, EMBASE, PsycInfo, Internet underground and governmental
      websites using the following keywords alone or in combination: designer drugs,
      club drugs, party drugs, GHB, synthetic cathinones, mephedrone, methylone,
      flephedrone, MDAI, and MDVP. Available epidemiological, neurobiological, and
      clinical data for each compound are described. There is evidence that negative
      health and social consequences may occur in recreational and chronic users. The
      addictive potential of designer drugs is not weak. Non-fatal overdoses and deaths
      related to GHB/GBL or synthetic cathinones have been reported. Clinicians must be
      careful with GBL or synthetic cathinones, which are being sold and used as
      substitutes for GHB and MDMA, respectively. Interventions for drug prevention and
      harm reduction in response to the use of these drugs should be implemented on the
      Internet and in recreational settings. Prevention, Information, Action, and
      Treatment are the main goals that must be addressed for this new potentially
      addictive problem.

PMID- 21960541
TI  - Analysis of NRG 'legal highs' in the UK: identification and formation of novel
      cathinones.
AB  - A large number of cathinone derivatives have shown a wide range of bioactive
      properties, attracting great interest from communities associated with
      pharmaceutical research. Some of these derivatives have gained popularity as so
      called recreational 'legal highs' due to their availability on the Internet and
      high street shops. A previous study described the qualitative analysis of 24
      'legal high' Energy-1 (NRG-1) and NRG-2 products obtained from 18 websites
      following the ban on mephedrone and derivatives in April 2010. The majority of
      these products contained a mixture of cathinones just carrying a new label. Here,
      three additional cathinone products have been detected; two from an NRG-1 sample
      and one from an NRG-3 sample. This report describes their identification. NRG-1
      sample 1 consisted of a mixture of 4 cathinones namely 4-fluoromethcathinone (1),
      1-(3,4-methylenedioxyphenyl)-2-(methylamino)pentan-1-one (pentylone, 2), 3,4
      methylenedioxy-alpha-pyrrolidinobutyrophenone (MDPBP, 3) and 3,4
      methylenedioxypyrovalerone (MDPV, 4). The sample labelled as NRG-3 (mislabelled
      with the chemical structure of mephedrone) consisted of a mixture of 4-methyl
      alpha-pyrrolidinopropiophenone (MPPP, 5) and (2), whereas the remaining NRG-1
      sample 2 (also mislabelled with the chemical structure of mephedrone) consisted
      of a mixture of (2) and (3). Qualitative analyses were carried out by GC-(EI/CI)
      MS, NMR spectroscopy and confirmation by preparation of standards. The
      preparation of brominated precursors carrying the 3,4-methylenedioxyphenyl
      nucleus revealed extensive alpha,alpha-dibromination: the mass spectral and NMR
      data of these intermediates are also presented and discussed.

PMID- 21960542
TI  - Potential impact of drug effects, availability, pharmacokinetics, and screening
      on estimates of drugs implicated in cases of assault.
AB  - Drug-facilitated sexual assault (DFSA) is a serious and troubling crime. It is
      important to know if and how different drugs might be used to facilitate assault
      in order to deter such crime. There are a number of ways in which drugs that are
      used for DFSA might not be detected by routine screens. The purpose of this
      analysis was to draw reasonable inferences regarding drugs with a high likelihood
      of being used for DFSA and not being detected by routine screens. National data
      from poison control centres, hospital emergency rooms, and law enforcement
      seizures were used to evaluate the relative magnitude of problems and illicit
      availability associated with different classes of drugs. General drug classes
      were examined to include additional drugs that might be used for DFSA on the
      basis of their amnesic effects, widespread availability, and pharmacokinetics
      (i.e. short half-life). The benzodiazepine-site ligands zolpidem and eszopiclone,
      'club drugs' GHB and ketamine, muscle relaxants such as carisoprodol, and
      antihistamines such as diphenhydramine were identified as drugs that might be
      used for DFSA and remain undetected by routine screens. Future studies that are
      designed to examine the role of these drugs in DFSA cases could provide better
      estimates of their use for DFSA. A better understanding of what is being missed
      in DFSA cases might help prioritize the development of new assays, provide
      rationale for the availability of particular assays for routine testing, and
      inform practitioners and the general public of the potential DFSA risks of
      certain drugs.

PMID- 21960543
TI  - Enzyme-assisted synthesis of the glucuronide conjugate of psilocin, an
      hallucinogenic component of magic mushrooms.
AB  - An enzyme-assisted synthesis of psilocin glucuronide (PCG), a metabolite excreted
      in the urine of magic mushroom (MM) users, is described. In the presence of
      Aroclor 1254 pretreated rat liver microsomes, psilocin and the cofactor UDPGA
      were incubated for 20 h. Purification by HPLC gave PCG in 19% yield (3.6 mg). The
      compound structure was characterized by MS and NMR. The milligram amounts of PCG
      produced by this method will allow the direct identification and quantification
      of PCG in the urine of MM users.

PMID- 21960544
TI  - Microwave-accelerated preparation and analytical characterization of 5-ethoxy-N,N
      dialkyl-[alpha,alpha,beta,beta-H(4) ]- and [alpha,alpha,beta,beta-D(4) ]
      tryptamines.
AB  - The increased interest in N,N-dialkyl tryptamines is a reflection of their
      diverse range of biologically active properties. Deuterated derivatives are of
      interest for use as internal standards in bioanalytical or pharmacological
      assays. The present study reports on the synthesis of twelve novel 5-ethoxy-N,N
      dialkyl-[alpha,alpha,beta,beta-H(4) ]-tryptamines and their
      [alpha,alpha,beta,beta-D(4) ]-counterparts following the Speeter and Anthony
      procedure. The normally time-consuming reduction step was carried out in 5 min
      under microwave-accelerated conditions. Good yields were obtained using
      tetrahydrofuran as the solvent at 150  degrees C. The resulting 24 tryptamines
      have been characterized by 1D/2D nuclear magnetic resonance spectroscopy and gas
      chromatography ion trap mass spectrometry. Differential fragmentation of side
      chain-related iminium ions has been observed as a key principle. Because many N,N
      dialkyltryptamines are available outside of traditional pharmaceutical supply
      chains as so-called 'research chemicals', the availability, as standards, of
      these new N,N-dialkyltryptamines will aid in identifiying novel tryptamines
      arising from these other souces. They should therefore be of immediate value
      within forensic, research, and public health contexts.

PMID- 21960545
TI  - Accurate identification of A-to-I RNA editing in human by transcriptome
      sequencing.
AB  - RNA editing enhances the diversity of gene products at the post-transcriptional
      level. Approaches for genome-wide identification of RNA editing face two main
      challenges: separating true editing sites from false discoveries and accurate
      estimation of editing levels. We developed an approach to analyze transcriptome
      sequencing data (RNA-seq) for global identification of RNA editing in cells for
      which whole-genome sequencing data are available. We applied the method to
      analyze RNA-seq data of a human glioblastoma cell line, U87MG. Around 10,000 DNA
      RNA differences were identified, the majority being putative A-to-I editing
      sites. These predicted A-to-I events were associated with a low false-discovery
      rate (~5%). Moreover, the estimated editing levels from RNA-seq correlated well
      with those based on traditional clonal sequencing. Our results further
      facilitated unbiased characterization of the sequence and evolutionary features
      flanking predicted A-to-I editing sites and discovery of a conserved RNA
      structural motif that may be functionally relevant to editing. Genes with
      predicted A-to-I editing were significantly enriched with those known to be
      involved in cancer, supporting the potential importance of cancer-specific RNA
      editing. A similar profile of DNA-RNA differences as in U87MG was predicted for
      another RNA-seq data set obtained from primary breast cancer samples. Remarkably,
      significant overlap exists between the putative editing sites of the two
      transcriptomes despite their difference in cell type, cancer type, and genomic
      backgrounds. Our approach enabled de novo identification of the RNA editome,
      which sets the stage for further mechanistic studies of this important step of
      post-transcriptional regulation.

PMID- 21960546
TI  - Peptidylarginine deiminases present in the airways during tobacco smoking and
      inflammation can citrullinate the host defense peptide LL-37, resulting in
      altered activities.
AB  - Bacterial colonization of the lower respiratory tract is frequently seen in
      chronic obstructive pulmonary disease (COPD), and may cause exacerbations leading
      to disease progression. Antimicrobial peptides comprise an important part of
      innate lung immunity, and not least the cathelicidin human cationic antimicrobial
      protein-18/LL-37. Peptidylarginine deiminases (PADIs) post-translationally modify
      proteins by converting cationic peptidylarginine residues to neutral
      peptidylcitrulline. An increased presence of PADI2 and citrullinated proteins was
      demonstrated in the lungs of smokers. In this study, preformed PADI4, stored in
      granulocytes and extracellularly in the lumina of bronchi, was found in lung
      tissue of individuals suffering from COPD. In vitro, recombinant human PADI2 and
      PADI4 both caused a time- and dose-dependent citrullination of LL-37. The
      citrullination resulted in impaired antibacterial activity against Staphylococcus
      aureus, Streptococcus pneumoniae, and nontypable Haemophilus influenzae, but less
      so against Pseudomonas aeruginosa. Using artificial lipid bilayers, we observed
      discrete differences when comparing the disrupting activity of native and
      citrullinated LL-37, suggesting that differences in cell wall composition are
      important during interactions with whole bacteria. Furthermore, citrullinated LL
      37 showed higher chemotactic activity against mononuclear leukocytes than did
      native LL-37, but was less efficient at neutralizing lipolysaccharide, and also
      in converting apoptotic neutrophils into a state of secondary necrosis. In
      addition, citrullinated LL-37 was more prone to degradation by proteases, whereas
      the V8 endopetidase of S. aureus cleaved the modified peptide at additional
      sites, compared with native LL-37. Together, these findings demonstrate novel
      mechanisms whereby the inflammation-dependent deiminases PADI2 and PADI4 can
      alter the activites of antibacterial polypeptides, affecting the course of
      inflammatory disorders such as COPD.

PMID- 21960547
TI  - Single-walled carbon nanotubes induce airway hyperreactivity and parenchymal
      injury in mice.
AB  - Inhalation of single-walled carbon nanotubes (SWCNTs) has raised serious concerns
      related to potential toxic effects in the respiratory system. This study examined
      possible SWCNT-induced toxic mechanisms in vivo in mice. The results indicated
      that a single intratracheal instillation of SWCNTs could induce airway
      hyperreactivity and airflow obstruction and confirmed previous findings of
      granulomatous changes in the lung parenchyma that persisted from 7 days to 6
      months after exposure. The irreversible lung pathology and functional airway
      alterations in the mouse model mimicked obstructive airway disease in humans.
      Transcriptomic analysis showed that SWCNTs might up-regulate proteinases
      (cathepsin K and matrix metalloproteinase [MMP]12), chemokines C-C motif ligands
      (CCL2 and CCL3), and several macrophage receptors (Toll-like receptor 2,
      macrophage scavenger receptor 1). Pathway analyses showed that NF-kappaB-related
      inflammatory responses and downstream signals affecting tissue remodeling
      dominated the pathologic process. The NF-kappaB inhibitor pyrrolidine
      dithiocarbamate attenuated SWCNT-induced airway hyperreactivity, chronic airway
      inflammation, and MMP12 and cathepsin K expression when administered in vivo,
      whereas a cathepsin K inhibitor could partially reduce airway hyperreactivity and
      granulomatous changes in the SWCNT-treated group. The up-regulation of cathepsin
      K and MMP12 by SWCNTs was further confirmed via in vitro coculture of
      bronchoalveolar macrophages with lung epithelial/mesenchymal cells but not in
      macrophages without coculture, indicating that SWCNT-induced MMP12 and cathespin
      K were cell-type specific and cell-cell interaction dependent. In conclusion,
      exposure to SWCNTs may cause irreversible obstructive airway disease.
      Nanotoxicogenomics uncovered novel mechanisms underlying SWCNT-induced lung
      diseases, implicating MMP12 and cathepsin K in the pathologic injury as potential
      biomarkers or therapeutic targets.

PMID- 21960548
TI  - Protective role of T-bet and Th1 cytokines in pulmonary graft-versus-host disease
      and peribronchiolar fibrosis.
AB  - T-box expressed in T cells (T-bet) is a critical transcription factor for T
      helper (Th) 1 responses. Although Th1 cells are thought to contribute to certain
      alloimmune responses, their role in pulmonary graft-versus-host disease (GVHD) is
      uncertain. We have established a murine model of acute pulmonary GVHD after
      hematopoietic cell transplant (HCT) and inhaled LPS exposure. We tested the
      hypothesis that pulmonary GVHD can occur independent of Th1 cells using T-bet
      deficient donors. B10.BR(H2(k)) mice underwent allogeneic (Allo) or syngeneic
      (Syn) HCT with cells from either C57Bl/6J(H2(b)) mice (Allo wild-type [WT] or
      SynWT) or C57Bl/6J mice lacking T-bet (AlloTbet(-/-) or SynTbet(-/-)). After HCT,
      mice were exposed daily to aerosolized LPS and subsequently bronchoalveolar
      lavage and lung tissue were analyzed for cytokines, lymphocytic inflammation,
      pathology, and fibrosis. Independent of LPS exposure, AlloTbet(-/-) mice
      developed pulmonary GVHD manifested by lymphocytic inflammation. Furthermore,
      AlloTbet(-/-) mice developed features of chronic pulmonary GVHD, including
      increased peribronchiolar fibrosis and collagen content. LPS exposure increased
      neutrophil recruitment and decreased static compliance in AlloTbet(-/-) mice as
      compared with LPS-exposed AlloWT mice or LPS-exposed SynTbet(-/-) mice. In
      addition, LPS-exposed AlloTbet(-/-) mice had increased pulmonary IL-17, IL-13,
      and Th17 cells, and diminished regulatory T cells compared with the other groups.
      Our results demonstrate that Th1 cytokines are dispensable in pulmonary GVHD. In
      the absence of T-bet, there is increased production of Th17 and Th2 cytokines
      that is associated with peribronchiolar fibrosis and is further enhanced by LPS.
      These results suggest that the interplay between local innate immunity and non
      Th1 T cell subsets contribute to chronic pulmonary GVHD.

PMID- 21960550
TI  - Hybridization among dominant tree species correlates positively with understory
      plant diversity.
AB  - PREMISE OF THE STUDY: Elucidating the factors that determine the abundance and
      distribution of species remains a central goal of ecology. It is well recognized
      that genetic differences among individual species can affect the distribution and
      species interactions of dependent taxa, but the ecological effects of genetic
      differences on taxa of the same trophic level remain much less understood. Our
      goal was to test the hypothesis that differences between related overstory tree
      species and their hybrids can influence the understory plant community in wild
      settings. METHODS: We conducted vegetation surveys in a riparian community with
      the overstory dominated by Populus fremontii, P. angustifolia, and their natural
      hybrids (referred to as cross types) along the Weber River in north central Utah,
      USA. Understory diversity and community composition, as well as edaphic
      properties, were compared under individual trees. KEY RESULTS: Diversity metrics
      differ under the three different tree cross types such that a greater species
      richness, diversity, and cover of understory plants exist under the hybrids
      compared with either of the parental taxa (30-54%, 40-48%, and 35-74% greater,
      respectively). The community composition of the understory also varied by cross
      type, whereby additional understory plant species cluster with hybrids, not with
      parental species. CONCLUSIONS: Genetic composition dictated by hybridization in
      the overstory can play a role in structuring the associated understory plants in
      natural communities-where a hybridized overstory correlates with a species-rich
      understory-and thus can have cascading effects on community members of the same
      trophic level. The underlying mechanism requires further investigation.

PMID- 21960551
TI  - Does polyembryony reduce seed germination and seedling development in Eriotheca
      pubescens (Malvaceae: Bombacoideae)?
AB  - PREMISE OF THE STUDY: Competition between siblings affect their growth and
      survival ability. An extreme situation is polyembryony, whereby siblings are
      exposed to competition from the beginning of their development. But its effect on
      plant reproduction is seldom tested. Eriotheca pubescens is a tree in the
      Cerrado, the Neotropical Savannas in Brazil, with apomictic/polyembryonic and
      sexual/monoembryonic populations. We tested the effect of polyembryony on
      germination, emergence, and growth in E. pubescens. This may have ecological
      consequences within the Cerrado, where seedling establishment is critical for
      species persistency and distribution. METHODS: We tested the effect of embryonic
      origin on germinability- and time-related parameters using seeds from different
      populations. We measured cultivated seedling growth continuously for 70 d and
      exhumed them after 9 mo to measure seedling biometry traits such as shoot, root,
      and seedling mass. We compared these traits with the number of seedlings emerged
      per seed and fitted data to a linear regression model. KEY RESULTS: Polyembryony
      reduced germinability and seedlings' initial growth in E. pubescens. Seedling
      traits and biomass decreased with the number of seedlings arising per seed. But
      the effect of polyembryony was mostly on initial seedling size and not on
      seedling growth rate. CONCLUSIONS: Polyembryony and apomixis affected germination
      and led to smaller seedlings compared with monoembryonic sexual counterparts.
      Although smaller, these extra seedlings may enhance per-seed survival chances in
      the Cerrado conditions of seasonal drought and frequent fires and explain the
      predominance of polyembryonic populations.

PMID- 21960549
TI  - Pneumocystis elicits a STAT6-dependent, strain-specific innate immune response
      and airway hyperresponsiveness.
AB  - It is widely held that exposure to pathogens such as fungi can be an agent of
      comorbidity, such as exacerbation of asthma or chronic obstructive pulmonary
      disease. Although many studies have examined allergic responses to fungi and
      their effects on pulmonary function, the possible pathologic implications of the
      early innate responses to fungal pathogens have not been explored. We examined
      early responses to the atypical fungus Pneumocystis in two common strains of mice
      in terms of overall immunological response and related pathology, such as cell
      damage and airway hyperresponsiveness (AHR). We found a strong strain-specific
      response in BALB/c mice that included recruitment of neutrophils, NK, NKT, and
      CD4 T cells. This response was accompanied by elevated indicators of lung damage
      (bronchoalveolar lavage fluid albumin and LDH) and profound AHR. This early
      response was absent in C57BL/6 mice, although both strains exhibited a later
      response associated with the clearance of Pneumocystis. We found that this AHR
      could not be attributed exclusively to the presence of recruited neutrophils,
      NKT, NK, or CD4 cells or to the actions of IFN-gamma or IL-4. However, in the
      absence of STAT6 signaling, AHR and inflammatory cell recruitment were virtually
      absent. Gene expression analysis indicated that this early response included
      activation of several transcription factors that could be involved in pulmonary
      remodeling. These results show that exposure to a fungus such as Pneumocystis can
      elicit pulmonary responses that may contribute to morbidity, even without prior
      sensitization, in the context of certain genetic backgrounds.

PMID- 21960552
TI  - Retinas of the diurnal rodent Arvicanthis ansorgei are highly resistant to
      experimentally induced stress and degeneration.
AB  - PURPOSE: Environmentally induced stress plays a significant role in retinal
      degeneration and blindness both in animals and in humans. Among such sources of
      stress, phototoxicity is well studied and has been shown to lead to photoreceptor
      specific loss in a number of species. However, the vast majority of studies have
      been conducted in nocturnal, albino rod-dominant rat and mouse strains, and the
      pertinence of such findings to human pathology and cone loss is debatable. The
      authors examined retinal vulnerability to damage in the diurnal murid rodent
      Arvicanthis ansorgei, a pigmented species with a large number of cones. METHODS:
      The authors used established protocols for exposing animals to a wide range of
      lighting conditions (variable intensity, duration, spectrum, previous light
      history, and time of exposure) and injecting N-methyl-N-nitrosourea (MNU); each
      procedure is reported to produce rapid and complete photoreceptor-specific
      damage. Animals then underwent electroretinography to record rod and cone
      function and were subsequently euthanized and used for immunohistochemical
      analysis of retinal structure and quantification of free fatty acids. RESULTS:
      These standard regimens produced no detectable detrimental effects on A. ansorgei
      retinal phenotype, function, or structure. Partial retinal damage in A. ansorgei
      was induced by very intense blue light or elevated doses of MNU. This resistance
      was not attributable to differences in lipid composition (specifically,
      docosahexaenoic acid) between A. ansorgei and susceptible strains of mice and
      rats. CONCLUSIONS: The retina of this species exhibits exceptionally high
      resistance to damage from light and toxins such as MNU.

PMID- 21960553
TI  - Human retinal pigment epithelium cells as functional models for the RPE in vivo.
AB  - PURPOSE: The two most commonly used in vitro models of the retinal pigment
      epithelium (RPE) are fetal human RPE (fhRPE) and ARPE-19 cells; however, studies
      of their barrier properties have produced contradictory results. To compare their
      utility as RPE models, their morphologic and functional characteristics were
      analyzed. METHODS: Monolayers of both cell types were grown on permeable membrane
      filters. Barrier function and cellular morphology were assessed by
      transepithelial resistance (TER) measurements and immunohistochemistry. Protein
      expression was evaluated by immunoblotting and ELISA assays, and retinoid
      metabolism characterized by HPLC. RESULTS: Both cultures developed tight
      junctions. However, only the fhRPE cells were pigmented, uniform in size and
      shape, expressed high levels of RPE markers, metabolized all-trans retinal, and
      developed high TER (>400 Omegacm(2)). The net secretion of pigment-epithelium
      derived factor (PEDF) was directed apically in both cultures, but fhRPE cells
      exhibited secretion rates a thousand-fold greater than in ARPE-19 cells. The net
      secretion of vascular endothelial growth factor (VEGF) was significantly higher
      in fhRPE cultures and the direction of this secretion was basolateral; while net
      secretion was apical in ARPE-19 cells. In fresh media, VEGF-E reduced TER in both
      cultures; however, in conditioned media fhRPE cells did not respond to VEGF-E
      administration, but retreatment of the conditioned media with anti-PEDF
      antibodies allowed fhRPE cells to fully respond to VEGF-E. CONCLUSIONS:
      Properties of fhRPE cells align with a functionally normal RPE in vivo, while
      ARPE-19 cells resemble a pathologic or aged RPE. These results suggest a utility
      for both cell types in understanding distinct, particular aspects of RPE
      function.

PMID- 21960554
TI  - Hypoxia-regulated retinal glial cell-specific promoter for potential gene therapy
      in disease.
AB  - PURPOSE: Retinal Muller cells span the retina and secrete several trophic factors
      and represent the functional link between blood vessels and neurons, making them
      attractive targets for gene therapy. Therefore, a hypoxia-regulated, retinal
      glial cell-specific vector was constructed and tested for its response to
      hypoxia. METHODS: A hybrid promoter containing domains of human glial fibrillary
      acidic protein (GFAP) and several hypoxia-responsive and aerobically silenced
      elements (HRSE) was incorporated separately into plasmid vectors for generation
      of self-complementary adeno-associated virus. Muller cells trasfected with
      plasmids or virus were compared with other cell lines using standard METHODS: The
      mouse model of oxygen-induced retinopathy (OIR) was used to analyze retinas from
      mice exposed to high oxygen or room air to evaluate the induction of the
      regulated promoter. RESULTS: The regulated promoter was silenced under aerobic
      conditions in comparison with unregulated promoter in Muller cells. Hypoxia
      induced a 12-fold and 16-fold increase in promoter activity in primary Muller
      cells and human Muller cell lines, respectively. In the OIR model, intravitreal
      injection of the regulated promoter at postnatal day 7 (P7) resulted in high
      levels of green fluorescent protein expression only in retinal Muller cells at
      P17. GFP expression was absent in retinas of mice only exposed to room air. In
      vivo studies confirm normoxia silencing, hypoxic induction, and cell specificity
      of the regulated promoter in the mouse retina. CONCLUSIONS: This hypoxia
      regulated, retinal glial cell-specific AAV vector provides a platform for gene
      therapy within regions of retinal hypoxia which are found in diabetic retinopathy
      and age-related macular degeneration.

PMID- 21960556
TI  - Visual prognostic value of optical coherence tomography and photopic negative
      response in chiasmal compression.
AB  - PURPOSE: To investigate the potential of the optical coherence tomography (OCT)
      measurement of retinal nerve fiber layer (RNFL) thickness and ganglion cell
      complex (GCC) area and photopic negative response (PhNR) for predicting
      postoperative visual outcome in chiasmal compression, prospectively. METHODS:
      Eighteen eyes of 18 patients undergoing chiasmal decompression surgery were
      prospectively assessed before, and 3 months after surgery with standard automated
      perimetry (SAP), OCT, and PhNR. Preoperative measurements were compared with 20
      eyes of 20 age-matched controls. Spearman's correlation and regression analyses
      were conducted to evaluate the relationship between preoperative RNFL thickness,
      GCC area, PhNR/b-wave amplitude ratio, postoperative mean deviation (MD) and
      temporal visual field sensitivity (1/Lambert). RESULTS: Preoperative measurements
      of RNFL thickness, GCC area, and PhNR/b-wave amplitude ratio were reduced
      significantly in patients compared with normal controls. Preoperative RNFL
      thickness of the temporal quadrant, GCC area, and PhNR/b-wave amplitude ratio
      were correlated significantly with postoperative MD and temporal visual field
      sensitivity (1/Lambert). CONCLUSIONS: An eye with the more demonstrable
      structural deterioration, as shown by reduced RNFL thickness and GCC area, and
      retinal ganglion cell dysfunction as shown by decreased PhNR/b-wave amplitude
      ratio was associated with the worse visual fields outcome. RNFL thickness and GCC
      area measurements using OCT and PhNR/b-wave amplitude ratio could be a useful
      prognostic indicator in the preoperative assessment of chiasmal compression.

PMID- 21960555
TI  - alphaVbeta6 integrin promotes corneal wound healing.
AB  - PURPOSE: To appreciate the role of the integrin alphavbeta6 in corneal wound
      repair, corneal debridement and keratectomy in beta6 knockout (beta6(-/-)) mice
      were examined. METHODS: Either a 2-mm debridement or keratectomy was made in
      129SVE wild type mice (WT) and beta6(-/-) mice and allowed to heal for up to 4
      months. The pattern of corneal restoration was studied "in vivo" by slit lamp and
      in tissue sections by means of both light and electron microscopy. In addition,
      alphavbeta6, alpha6beta4, laminin, and fibronectin were evaluated by indirect
      immunofluorescence microscopy and/or Western blot analysis. RESULTS: alphavbeta6
      expression was upregulated in migrating corneal epithelium after a keratectomy.
      Healing rates were unaffected in debridement wounds, but were significantly
      slowed in keratectomy wounds. Most dramatically, mice lacking alphavbeta6 had a
      severe defect in basement membrane zone (BMZ) regeneration. Levels of laminin
      were greatly reduced and no BMZ reformation was observed in transmission electron
      microscopy (TEM). In addition, hemidesmosome reformation was also impaired in the
      beta6(-/-) mice. Analysis of the hemidesmosome component alpha6beta4 indicated
      that normal amounts of this integrin were synthesized, suggesting that the defect
      was in reassembly of the hemidesmosomes. Finally, fibronectin persisted in the
      BMZ for as long as 4 months after keratectomy in the beta6(-/-) mice.
      CONCLUSIONS: It is hypothesized that the lack of alphavbeta6 leads to reduced
      laminin production during wound repair. This lack of laminin prevents reassembly
      of the BMZ and mature hemidesmosomes after keratectomy in beta6(-/-) mice.

PMID- 21960557
TI  - Histopathology of the trabecular meshwork and Schlemm's canal in primary angle
      closure glaucoma.
AB  - PURPOSE: To investigate the detailed histopathology of trabecular meshwork
      changes associated with primary angle closure glaucoma (PACG). METHODS: Thirty
      trabecular blocks obtained from trabeculectomy (TLE) of 25 PACG patients were
      embedded in paraffin for immunohistochemical staining of thrombomodulin, CD68, D2
      40, and epon for transmission electron microscopy. Eleven TLE blocks obtained
      from normal-tension glaucoma patients were used as a control. Histologic changes
      of outflow routes were analyzed by comparing the existence of iridotomy,
      gonioscopy-evaluated angle closure, intraocular pressure (IOP), episodes of acute
      attack, visual field defect classified by Aulhorn-Greve, anterior chamber depth,
      lens thickness, and axial length. RESULTS: Occlusion of the Schlemm's canal (SC)
      of <150 MUm was observed in 11 eyes, which significantly correlated with
      gonioscopy-evaluated angle closure (T = 19.33 > chi2 (f,alpha) = 9.488). Moderate
      correlation between SC occlusion and IOP before TLE was also observed
      (correlation coefficient: -0.540). Slightly negative or no correlations were
      found between SC occlusion and the other parameters. Thinned SC endothelium at
      the junction or degenerated SC endothelium and various degrees of SC occlusion
      and fusion of the trabecular beams where trabecular cells degenerated with
      damaged mitochondria were the general findings in the PACG eyes involved in this
      study. CONCLUSIONS: Persistent trabecular-iris contact or peripheral anterior
      synechia may block aqueous outflow resulting in a progressive process of SC
      endothelial damage and subsequent SC occlusion, as well as trabecular cell damage
      possibly due to impairment of mitochondrial function and subsequent fusion of the
      trabecular beams. These changes may be the reason for residual glaucoma after
      laser iridotomy or cataract surgery.

PMID- 21960558
TI  - Differences in clinical characteristics of head injuries to snowboarders by skill
      level.
AB  - BACKGROUND: Many reports have compared head injuries between snowboarding and
      skiing. However, detailed studies comparing snowboarding head injuries between
      beginners and intermediates/experts have been lacking. PURPOSE: The authors
      investigated differences in clinical characteristics of head injuries to
      snowboarders between beginners (group B) and intermediates/experts (group IE).
      STUDY DESIGN: Descriptive epidemiology study. METHODS: The study population
      included 2367 patients treated at Saito Memorial Hospital and Yuzawa Community
      Health Medical Center, Niigata Prefecture, Japan, during 9 seasons from 1999-2000
      to 2007-2008. RESULTS: Group B comprised 959 patients (mean age, 23.0 years; 52%
      males). Group IE comprised 1408 patients (mean age, 24.8 years; 72% males).
      Accidents in group B predominantly occurred as falls on gentle slopes (37%) and
      intermediate slopes (33%), whereas accidents in group IE occurred mostly during
      jumping (48%). The impact point on the head was predominantly occipital in both
      groups, but group IE showed a significantly higher frequency of trauma to the
      frontal region. The ratio of neurologic abnormalities was significantly higher in
      group IE. However, the ratio of surgical cases was significantly higher in group
      B (n = 10, 1.04%) than in group IE (n = 5, 0.36%). More acute subdural hematomas
      were seen in group B, but more fractures, contusions, and acute epidural
      hematomas were seen in group IE. Four moderate disabilities, 2 comatose patients,
      and 2 deaths were seen in group B, and 1 moderate disability, 2 severe
      disabilities, and 1 death were seen in group IE during this study. CONCLUSION:
      The data suggest significant differences in clinical states between beginners and
      intermediates/experts. Preventive methods for severe head injuries among
      snowboarders need to be devised based on differences in skill levels.

PMID- 21960559
TI  - Midterm results of the treatment of cartilage defects in the knee using alginate
      beads containing human mature allogenic chondrocytes.
AB  - BACKGROUND: The treatment of chondral lesions is still an important challenge for
      the orthopaedic surgeon. Attempts have been made to restore cartilage lesions by
      filling the defects with a temporary biocompatible matrix. PURPOSE: The authors
      present their midterm experience with the implantation of alginate beads
      containing human mature allogenic chondrocytes for the treatment of cartilage
      lesions in the knee. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A
      biodegradable, alginate-based biocompatible scaffold containing human mature
      allogenic chondrocytes was used for the treatment of cartilage lesions in the
      knee. Twenty-one patients were clinically prospectively evaluated with use of the
      Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and a
      visual analog scale (VAS). The mean follow-up time was 6.3 years (range, 5-8
      years). Magnetic resonance imaging (MRI) data were analyzed based on the MOCART
      (Magnetic Resonance Observation of Cartilage Repair Tissue) system, allowing
      morphologic assessment of the repair tissue. Magnetic resonance images were taken
      at 1 year of follow-up and at a mean follow-up of 6.1 years (range, 5-7 years).
      RESULTS: During the follow-up period, the WOMAC and VAS scores improved
      significantly. No signs of clinical deterioration or adverse reactions to the
      alginate beads/allogenic chondrocyte implantation were observed. Four failures
      occurred during the follow-up period in this study (19.05%). The MOCART scores
      were moderate and remained stable in time. CONCLUSION: This investigation
      provided useful information on the efficacy of the implantation of alginate beads
      containing human mature allogenic chondrocytes for the treatment of cartilage
      lesions in the knee. The midterm clinical outcome of the presented technique was
      satisfactory. However, these results were not confirmed by the MRI findings.

PMID- 21960560
TI  - A mixed treatment comparison of the efficacy of anti-TNF agents in rheumatoid
      arthritis for methotrexate non-responders demonstrates differences between
      treatments: a Bayesian approach.
AB  - BACKGROUND: A number of tumour necrosis factor alpha (TNFalpha) antagonists (anti
      TNFalpha) are available to treat rheumatoid arthritis. All of these have
      demonstrated considerable efficacy in placebo controlled trials, but few head-to
      head comparisons exist to date. This work's objective is to estimate the relative
      efficacy among licensed anti-TNFs in patients who have had an inadequate response
      to methotrexate (MTX). Different outcome measures are used to highlight the
      advantages of continuous measures in such analyses. METHODS: A systematic review
      identified randomised controlled trials comparing the efficacy of licensed anti
      TNFalpha agents with placebo at 24 weeks in patients who have had an inadequate
      response to MTX. Relative efficacy was estimated using Bayesian mixed treatment
      comparison (MTC) models. Three different outcome measures were used: RR of
      achieving an American College of Rheumatology (ACR) 20 and ACR50 response and the
      percentage improvement in Health Assessment Questionnaire (HAQ) score. RESULTS:
      16 published trials were included in the analysis. All anti-TNFs show
      considerably improved efficacy over placebo. The MTC results also provide
      evidence of some differences in efficacy of the TNFalpha antagonists. Etanercept
      appears superior to infliximab and golimumab, and certolizumab to infliximab and
      adalimumab. ACR results indicate improved efficacy of certolizumab over
      golimumab. On HAQ analysis, adalimumab, certolizumab, etanercept and golimumab
      appear superior to infliximab, and etanercept shows improved efficacy compared
      with adalimumab. CONCLUSIONS: There are differences in efficacy among the
      TNFalpha antagonists. In a MTC, a continuous outcome measure has more strength to
      detect such differences than a binomial outcome measure because of its enhanced
      sensitivity to change.

PMID- 21960561
TI  - Focused ultrasound-mediated drug delivery from microbubbles reduces drug dose
      necessary for therapeutic effect on neointima formation--brief report.
AB  - OBJECTIVE: We hypothesized that (1) neointima formation in a rat carotid balloon
      injury model could be reduced in vivo following targeted ultrasound delivery of
      rapamycin microbubbles (RMBs), and (2) the addition of dual-mode ultrasound
      decreases the total amount of drug needed to reduce neointima formation. METHODS
      AND RESULTS: Balloon injury was performed in rat carotids to induce neointima
      formation. High or low doses of RMBs were injected intravenously and ruptured at
      the site of injury with ultrasound. Compared with nontreated injured arteries,
      neointima formation was reduced by 0% and 35.9% with 10(8) RMBs and by 28.7% and
      34.9% in arteries treated with 10(9) RMBs with and without ultrasound,
      respectively. CONCLUSIONS: Without ultrasound, 10-fold higher concentrations of
      RMBs were needed to reduce neointima formation by at least 28%, whereas 10(8)
      RMBs combined with ultrasound were sufficient to achieve the same therapeutic
      effect, demonstrating that this technology may have promise for localized potent
      drug therapy.

PMID- 21960562
TI  - Activation of T lymphocytes in atherosclerotic plaques.
AB  - OBJECTIVE: To decipher the immunologic mechanisms of plaque maturation and
      rupture, it is necessary to analyze the phenotypes and distribution of individual
      lymphocytes that migrate to the plaques, as well as their activation at different
      stages of plaque formation. METHODS AND RESULTS: We developed a protocol to
      isolate plaque-residing immune cells and analyze their status using polychromatic
      flow cytometry. We found that the composition and phenotype of T lymphocytes in
      the plaques differs from that in blood. CD4 and, in particular, CD8(+) T cells in
      plaques are highly activated; the fraction of CD8 T cells coexpressing CD25 and
      human leukocyte antigen-D related in plaques was 6 times as large as in blood.
      CONCLUSIONS: The first flow-cytoanalysis of individual T cells in atherosclerotic
      plaques indicates that plaques represent a separate immunologic compartment from
      blood with lymphocytes characterized by a high level of T-cell activation, which
      is compatible with the presence of antigen(s) that trigger infiltration
      activation of these cells. The ability to isolate and characterize these cells
      may lead to the identification of such antigens.

PMID- 21960563
TI  - MyD88 deficiency attenuates angiotensin II-induced abdominal aortic aneurysm
      formation independent of signaling through Toll-like receptors 2 and 4.
AB  - OBJECTIVE: The purpose of this study was to determine whether myeloid
      differentiation factor 88 (MyD88) and its related Toll-like receptors (TLRs) 2
      and 4 contributed to the development of angiotensin II (AngII)-induced abdominal
      aortic aneurysms (AAAs) and atherosclerosis. METHODS AND RESULTS: AngII was
      infused into either apoE(-/-) or LDL receptor (LDLR)(-/-) male mice that were
      either MyD88(+/+) or (-/-). MyD88 deficiency profoundly reduced AngII-induced
      AAAs and atherosclerosis in both strains. To define whether deficiency of
      specific TLRs had similar effects, AngII was infused into LDLR(-/-) mice that
      were also deficient in either TLR2 or TLR4. TLR2 deficiency had no effect on AAA
      development but inhibited atherosclerosis. In contrast, TLR4 deficiency
      attenuated both AAAs and atherosclerosis. To resolve whether MyD88 and TLR4
      exerted their effects through cells of hematopoietic lineage, LDLR(-/-) mice were
      lethally irradiated and repopulated with bone marrow-derived cells from either
      MyD88 or TLR4 strains. MyD88 deficiency in bone marrow-derived cells profoundly
      reduced both AngII-induced AAAs and atherosclerosis. However, TLR4 deficiency in
      bone marrow-derived cells had no effect on either pathology. CONCLUSIONS: These
      studies demonstrate that MyD88 deficiency in leukocytes profoundly reduces AngII
      induced AAAs and atherosclerosis via mechanisms independent of either TLR2 or
      TLR4.

PMID- 21960564
TI  - Oxytocin mediates social neuroprotection after cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: The reduced incidence, morbidity, and mortality of stroke
      among humans with strong social support have been well-documented; however, the
      mechanisms underlying these socially mediated phenomena remain unknown, but may
      involve oxytocin (OT), a hormone that modulates some aspects of social behavior
      in humans and other animals. METHODS: In the present study, adult male mice were
      socially isolated (housed individually) or socially paired (housed with an
      ovariectomized female); social pairing increased hypothalamic OT gene expression.
      To determine whether a causal relationship exists between increased OT and
      improved stroke outcome, mice were treated with exogenous OT or OT receptor
      antagonist beginning 1 week before induction of experimental stroke via middle
      cerebral artery occlusion. RESULTS: Relative to social isolation, social housing
      attenuated infarct size, neuroinflammation, and oxidative stress following
      experimental stroke; the neuroprotective effect of social housing was eliminated
      by receptor antagonist treatment. In contrast, administration of OT to socially
      isolated mice reproduced the neuroprotection conferred by social housing. We
      further report evidence for a direct suppressive action of OT on cultured
      microglia, which is a key instigator in the development of neuroinflammation
      after cerebral ischemia. CONCLUSIONS: These findings support the hypothesis that
      OT mediates the neuroprotective effect of social interaction on stroke outcome.

PMID- 21960565
TI  - "Won't you be my neighbor?": deciphering the mechanisms of neuroprotection
      induced by social interaction.

PMID- 21960566
TI  - Letter by Naggara et al regarding article, "Are distal protection devices
      'protective' during carotid angioplasty and stenting?".

PMID- 21960567
TI  - Velocity criteria for intracranial stenosis revisited: an international
      multicenter study of transcranial Doppler and digital subtraction angiography.
AB  - BACKGROUND AND PURPOSE: Intracranial atherosclerotic disease is associated with a
      high risk of stroke recurrence. We aimed to determine accuracy of transcranial
      Doppler screening at laboratories that share the same standardized scanning
      protocol. METHODS: Patients with symptoms of cerebral ischemia were prospectively
      studied. Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA)
      criteria were used for identification of >=50% stenosis. We determined velocity
      cutoffs for >=70% stenosis on digital subtraction angiography by Warfarin-Aspirin
      Symptomatic Intracranial Disease criteria and evaluated novel
      stenotic/prestenotic ratio and low-velocity criteria. RESULTS: A total of 102
      patients with intracranial atherosclerotic disease (age 57+/-13 years; 72% men;
      median National Institutes of Health Stroke Scale 3, interquartile range 6)
      provided 690 transcranial Doppler/digital subtraction angiography vessel pairs.
      On digital subtraction angiography, >=50% stenosis was found in 97 and >=70%
      stenosis in 62 arteries. Predictive values for transcranial Doppler SONIA
      criteria were similar (P>0.9) between middle cerebral artery (sensitivity 78%,
      specificity 93%, positive predictive value 73%, negative predictive value 94%,
      and overall accuracy 90%) and vertebral artery/basilar artery (69%, 98%, 88%,
      93%, and 92%). As a single velocity criterion, most sensitive mean flow velocity
      thresholds for >=70% stenosis were: middle cerebral artery>120 cm/s (71%) and
      vertebral artery/basilar artery>110 cm/s (55%). Optimal combined criteria for
      >=70% stenosis were: middle cerebral artery>120 cm/s, or stenotic/prestenotic
      ratio>=3, or low velocity (sensitivity 91%, specificity 80%, receiver operating
      characteristic 0.858), and vertebral artery/basilar artery>110 cm/s or
      stenotic/prestenotic ratio>=3 (60%, 95%, 0.769, respectively). CONCLUSIONS: At
      laboratories with a standardized scanning protocol, SONIA mean flow velocity
      criteria remain reliably predictive of >=50% stenosis. Novel velocity/ratio
      criteria for >=70% stenosis increased sensitivity and showed good agreement with
      invasive angiography.

PMID- 21960568
TI  - Obesity paradox and stroke: noticing the (fat) man behind the curtain.

PMID- 21960569
TI  - Sea-level assessment of dynamic cerebral autoregulation predicts susceptibility
      to acute mountain sickness at high altitude.
AB  - BACKGROUND AND PURPOSE: Dynamic cerebral autoregulation is impaired in subjects
      who develop acute mountain sickness (AMS), a neurological disorder characterized
      by headache. The present study examined if the normoxic sea-level measurement of
      dynamic cerebral autoregulation would predict subsequent susceptibility to AMS
      during rapid ascent to terrestrial high altitude. METHODS: A dynamic cerebral
      autoregulation index was determined in 18 subjects at sea level from continuous
      recordings of middle cerebral artery blood flow velocity (Doppler
      ultrasonography) and arterial blood pressure (finger photoplethysmography) after
      recovery from transiently induced hypotension. Six hours after passive ascent to
      3800 m (Mt Elbrus, Russia), the Lake Louise and Environmental Symptoms Cerebral
      Symptoms questionnaires were used to assess AMS. RESULTS: AMS scores increased
      markedly at high-altitude (Lake Louise: +3+/-2 points, P=0.001 and Environmental
      Symptoms Cerebral Symptoms: +0.6+/-0.9 points, P=0.0003 versus sea level).
      Inverse relationships were observed between the sea-level autoregulation index
      score and the high-altitude-induced increases in the Lake Louise (r=-0.62,
      P=0.007) and Environmental Symptoms Cerebral Symptoms (r=-0.78, P=0.01) scores.
      One subject with a history of high-altitude pulmonary and cerebral edema
      presented with the lowest sea-level autoregulation index score (3.7 versus group:
      6.2+/-1.0 points) and later developed high-altitude cerebral edema at 4800 m
      during the summit bid. CONCLUSIONS: These findings suggest that a lower baseline
      autoregulation index may be considered a potential risk factor for AMS. This
      laboratory measurement may prove a useful screening tool for the expedition
      doctor when considering targeted pharmacological prophylaxis in individuals
      deemed "AMS-susceptible."

PMID- 21960570
TI  - Late-phase contrast-enhanced ultrasound reflects biological features of
      instability in human carotid atherosclerosis.
AB  - BACKGROUND AND PURPOSE: Development of translational functional imaging
      modalities for atherosclerosis risk stratification is sought for stroke
      prediction. Our group has developed late-phase contrast-enhanced ultrasound (LP
      CEUS) to quantify microbubble contrast retention within carotid atherosclerosis
      and shown it to separate asymptomatic plaques from those responsible for recent
      cerebrovascular events. We hypothesized that microbubbles are retained in areas
      of plaque inflammation, aiming to examine whether LP-CEUS signal reflects plaque
      biology. METHODS: Subjects awaiting carotid endarterectomy (n=31) underwent axial
      LP-CEUS and diseased intimal segments were symmetrically divided in the long
      axis. Half-specimens underwent quantitative immunohistochemical analysis for CD68
      (macrophages) and CD31 (angiogenesis). Half-specimens were processed for atheroma
      cell culture and supernatant collected at 24 hours for multianalyte profiling for
      34 analytes. RESULTS: Percentage area immunopositivity was significantly higher
      in subjects in which normalized plaque late-phase intensity was >=0 versus <0
      (CD68 mean 11.8 versus 6.68, P=0.004; CD31 mean 9.45 versus 4.82, P=0.025).
      Interleukin-6, matrix metalloproteinase-1, and matrix metalloproteinase-3 were
      significantly higher by multianalyte profiling when LP-CEUS was >=0. CONCLUSIONS:
      LP-CEUS reflects biological features of inflammation and angiogenesis, key
      features predisposing to plaque rupture. Further investigation of LP-CEUS as a
      tissue-specific marker of inflammation for risk stratification of carotid
      atherosclerosis is warranted.

PMID- 21960571
TI  - Failure of cerebral hemodynamic selection in general or of specific positron
      emission tomography methodology?: Carotid Occlusion Surgery Study (COSS).
AB  - BACKGROUND AND PURPOSE: The Carotid Occlusion Surgery Study (COSS) was an
      improvement over the Extracranial-Intracranial Bypass Study, which did not
      utilize physiological selection. To assess possible reasons for early closure of
      the COSS trial, we reviewed COSS methods used to identify high-risk patients and
      compared results with separate quantitative data. METHODS: Increased oxygen
      extraction fraction (OEF) by positron emission tomography is a gold standard for
      ischemia, but the specific thresholds and equivalency of the semiquantitative OEF
      ratio utilized in COSS and quantitative OEF are at issue. RESULTS: The
      semiquantitative hemispheric OEF ratio used in COSS did not identify the same
      group of patients as did quantitative OEF using a threshold of 50%. CONCLUSIONS:
      The failure of COSS is likely caused by a failure of the semiquantitative,
      hemispheric OEF ratio method rather than by the selection for bypass based on
      hemodynamic compromise.

PMID- 21960572
TI  - Plasma alpha-melanocyte stimulating hormone predicts outcome in ischemic stroke.
AB  - BACKGROUND AND PURPOSE: alpha-Melanocyte stimulating hormone (alpha-MSH) is an
      endogenously produced neuropeptide derived from the same precursor as
      adrenocorticotropic hormone. alpha-MSH has profound immunomodulatory properties
      and may also be neuroprotective. Nothing is known about alpha-MSH and changes in
      its plasma concentrations in patients with acute ischemic stroke. METHODS: In
      this prospective observational study, plasma concentrations of alpha-MSH,
      adrenocorticotropic hormone, cortisol, and interleukin 6 were assessed
      longitudinally over the course of 1 year after stroke onset in 111 patients.
      Logistic regression was used to the effect of initial plasma alpha-MSH,
      adrenocorticotropic hormone, cortisol, and interleukin 6 on long-term outcome.
      RESULTS: There was an early decrease in plasma alpha-MSH in patients with severe
      stroke (National Institutes of Health Stroke Scale>=17) that normalized over the
      course of the year; these same patients evidenced elevations in plasma cortisol
      and interleukin 6. Higher initial plasma alpha-MSH, but not adrenocorticotropic
      hormone, cortisol, or interleukin 6, was independently predictive of good long
      term outcome. CONCLUSIONS: This research is the first to study endogenous changes
      in plasma alpha-MSH after stroke. The independent effect of early plasma alpha
      MSH on stroke outcome, as well as a growing body of experimental data
      demonstrating improved stroke outcome with exogenous alpha-MSH administration,
      suggests a potential therapeutic role for alpha-MSH in the treatment of stroke.

PMID- 21960573
TI  - Rapid reversal of anticoagulation prevents excessive secondary hemorrhage after
      thrombolysis in a thromboembolic model in rats.
AB  - BACKGROUND AND PURPOSE: Thrombolysis is the only approved therapy for ischemic
      stroke, but secondary hemorrhage is a severe complication. Because oral
      anticoagulants are believed to increase the risk of hemorrhage, thrombolysis is
      usually contraindicated in patients on vitamin K antagonists. We studied whether
      thrombolysis in a thromboembolic middle cerebral artery occlusion model in rats
      pretreated with warfarin increases secondary hemorrhage, and whether substitution
      of coagulation factors before thrombolysis prevents hemorrhagic complications.
      METHODS: Wistar rats were anticoagulated using warfarin in drinking water (0.4
      mg/kg per 24 hours). Strength of anticoagulation was monitored using benchside
      international normalized ratio (INR) coagulometry. Two hours after middle
      cerebral artery occlusion, recombinant tissue-type plasminogen activator (9
      mg/kg) was administered. Two of 5 groups of animals received prothrombin complex
      concentrate (PCC, 50 U/kg) 15 minutes before thrombolysis. Serial magnetic
      resonance imaging was performed 20 minutes, 2.5 hours, and 24 hours after middle
      cerebral artery occlusion. Secondary hemorrhage was quantified on T2* magnetic
      resonance images as previously established. RESULTS: Severity of hypoperfusion on
      initial perfusion-weighted imaging -magnetic resonance did not differ among
      groups. Thrombolysis resulted in successful reperfusion in all groups.
      Anticoagulated animals had significantly more secondary hemorrhage and a higher
      mortality rate compared with nonanticoagulated animals. PCC rapidly reversed the
      increased international normalized ratio. Although PCC failed to prevent
      hemorrhage in the strongly anticoagulated, it reduced the incidence of severe
      hemorrhage in moderately anticoagulated rats (INR, 2-3) to the level of
      nonanticoagulated controls. CONCLUSIONS: Preceding anticoagulation increases risk
      and extent of secondary hemorrhage after thrombolysis. Reversal of moderate
      anticoagulation using PCC may allow thrombolytic therapy without increasing the
      risk of secondary hemorrhage.

PMID- 21960574
TI  - Extending the time window for endovascular procedures according to collateral
      pial circulation.
AB  - BACKGROUND AND PURPOSE: Good collateral pial circulation (CPC) predicts a
      favorable outcome in patients undergoing intra-arterial procedures. We aimed to
      determine if CPC status may be used to decide about pursuing recanalization
      efforts. METHODS: Pial collateral score (0-5) was determined on initial
      angiogram. We considered good CPC when pial collateral score<3, defined total
      time of ischemia (TTI) as onset-to-recanalization time, and clinical
      improvement>4-point decline in admission-discharge National Institutes of Health
      Stroke Scale. RESULTS: We studied CPC in 61 patients (31 middle cerebral artery,
      30 internal carotid artery). Good CPC patients (n=21 [34%]) had lower discharge
      National Institutes of Health Stroke Scale score (7 versus 21; P=0.02) and
      smaller infarcts (56 mL versus 238 mL; P<0.001). In poor CPC patients, a receiver
      operating characteristic curve defined a TTI cutoff point<300 minutes
      (sensitivity 67%, specificity 75%) that better predicted clinical improvement
      (TTI<300: 66.7% versus TTI>300: 25%; P=0.05). For good CPC patients, no temporal
      cutoff point could be defined. Although clinical improvement was similar for
      patients recanalizing within 300 minutes (poor CPC: 60% versus good CPC: 85.7%;
      P=0.35), the likelihood of clinical improvement was 3-fold higher after 300
      minutes only in good CPC patients (23.1% versus 90.1%; P=0.01). Similarly,
      infarct volume was reduced 7-fold in good as compared with poor CPC patients only
      when TTI>300 minutes (TTI<300: poor CPC: 145 mL versus good CPC: 93 mL; P=0.56
      and TTI>300: poor CPC: 217 mL versus good CPC: 33 mL; P<0.01). After adjusting
      for age and baseline National Institutes of Health Stroke Scale score, TTI<300
      emerged as an independent predictor of clinical improvement in poor CPC patients
      (OR, 6.6; 95% CI, 1.01-44.3; P=0.05) but not in good CPC patients. In a logistic
      regression, good CPC independently predicted clinical improvement after adjusting
      for TTI, admission National Institutes of Health Stroke Scale score, and age (OR,
      12.5; 95% CI, 1.6-74.8; P=0.016). CONCLUSIONS: Good CPC predicts better clinical
      response to intra-arterial treatment beyond 5 hours from onset. In patients with
      stroke receiving endovascular treatment, identification of good CPC may help
      physicians when considering pursuing recanalization efforts in late time windows.

PMID- 21960575
TI  - alpha7 nicotinic acetylcholine receptor agonist PNU-282987 attenuates early brain
      injury in a perforation model of subarachnoid hemorrhage in rats.
AB  - BACKGROUND AND PURPOSE: Early brain injury is an important pathological process
      after subarachnoid hemorrhage (SAH). The goal of this study was to evaluate
      whether the alpha7 nicotinic acetylcholine receptor (alpha7nAChR) agonist PNU
      282987 attenuates early brain injury after SAH and whether alpha7nAChR
      stimulation is associated with down-regulation of caspase activity via
      phosphatidylinositol 3-kinase-Akt signaling. METHODS: The perforation model of
      SAH was performed, and neurological score, body weight loss, and brain water
      content were evaluated 24 and 72 hours after surgery. Western blot and
      immunohistochemistry were used for quantification and localization of
      phosphorylated Akt and cleaved caspase 3. Neuronal cell death was quantified with
      TUNEL staining. alpha7nAChR antagonist methylcaconitine and phosphatidylinositol
      3-kinase inhibitor wortmannin were used to manipulate the proposed pathway, and
      results were quantified with Western blot. RESULTS: PNU-282987 improved
      neurological deficits both 24 and 72 hours after surgery and reduced brain water
      content in left hemispheres 24 hours after surgery. PNU-282987 significantly
      increased phosphorylated Akt levels and significantly decreased cleaved caspase 3
      levels in ipsilateral hemispheres after SAH. Methylcaconitine and wortmannin
      reversed effects of treatment. Phosphorylated Akt and cleaved caspase 3 were
      colocalized to neurons in the ipsilateral basal cortex. Phosphorylated Akt was
      mainly localized in TUNEL-negative cells. PNU-282987 significantly reduced
      neuronal cell death in the ipsilateral basal cortex. CONCLUSIONS: alpha7nAChR
      stimulation decreased neuronal cell death and brain edema and improved
      neurological status in a rat perforation model of SAH. alpha7nAChR stimulation is
      associated with increasing phosphorylation of Akt and decreasing cleaved caspase
      3 levels in neurons.

PMID- 21960576
TI  - Obesity and recurrent vascular risk after a recent ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Although obesity is an established risk factor for the
      occurrence of a primary stroke, little is known about the impact of baseline
      obesity on recurrent vascular risk among patients with recently symptomatic
      cerebrovascular disease. We evaluated the association of obesity with future
      vascular risk in patients with a recent history of stroke. METHODS: We analyzed
      the database of a multicenter trial involving 20 332 patients with recent
      ischemic stroke followed for 2.5 years. Subjects were divided into 3 groups
      according to recognized body mass index categories representing lean, overweight,
      and obese. Primary outcome was time to first recurrent stroke and secondary
      outcome time to stroke, myocardial infarction, or vascular death. The independent
      association of obesity with outcome was assessed by controlling for other known
      risk factors. RESULTS: Of 20 246 eligible subjects, 4805 (24%) were obese. After
      adjusting for confounders, compared with the lean group, being overweight (hazard
      ratio, 0.95; 95% CI, 0.85-1.06) or obese (hazard ratio, 0.95; 95% CI, 0.83-1.08)
      was not associated with increased recurrent stroke risk, but being overweight
      (hazard ratio, 0.84; 95% CI, 0.77-0.92) or obese (hazard ratio, 0.86; 95% CI,
      0.77-0.96) was associated with lower risk of a major vascular event. CONCLUSIONS:
      Obesity is not related to recurrent stroke risk, but obese patients with stroke
      are at lower overall vascular risk than their leaner counterparts, supporting the
      widely held notion of the existence of a cardiovascular "obesity paradox."

PMID- 21960577
TI  - Extent of hypoattenuation on CT angiography source images in basilar artery
      occlusion: prognostic value in the Basilar Artery International Cooperation
      Study.
AB  - BACKGROUND AND PURPOSE: The posterior circulation Acute Stroke Prognosis Early CT
      Score (pc-ASPECTS) quantifies the extent of early ischemic changes in the
      posterior circulation with a 10-point grading system. We hypothesized that pc
      ASPECTS applied to CT angiography source images predicts functional outcome of
      patients in the Basilar Artery International Cooperation Study (BASICS). METHODS:
      BASICS was a prospective, observational registry of consecutive patients with
      acute symptomatic basilar artery occlusion. Functional outcome was assessed at 1
      month. We applied pc-ASPECTS to CT angiography source images of patients with CT
      angiography for confirmation of basilar artery occlusion. We calculated
      unadjusted and adjusted risk ratios (RRs) of pc-ASPECTS dichotomized at >=8
      versus <8. Primary outcome measure was favorable outcome (modified Rankin Scale
      scores 0-3). Secondary outcome measures were mortality and functional
      independence (modified Rankin Scale scores 0-2). RESULTS: Of 158 patients
      included, 78 patients had a CT angiography source images pc-ASPECTS>=8. Patients
      with a pc-ASPECTS>=8 more often had a favorable outcome than patients with a pc
      ASPECTS<8 (crude RR, 1.7; 95% CI, 0.98-3.0). After adjustment for age, baseline
      National Institutes of Health Stroke Scale score, and thrombolysis, pc-ASPECTS>=8
      was not related to favorable outcome (RR, 1.3; 95% CI, 0.8-2.2), but it was
      related to reduced mortality (RR, 0.7; 95% CI, 0.5-0.98) and functional
      independence (RR, 2.0; 95% CI, 1.1-3.8). In post hoc analysis, pc-ASPECTS
      dichotomized at >=6 versus <6 predicted a favorable outcome (adjusted RR, 3.1;
      95% CI, 1.2-7.5). CONCLUSIONS: pc-ASPECTS on CT angiography source images
      independently predicted death and functional independence at 1 month in the CT
      angiography subgroup of patients in the BASICS registry.

PMID- 21960578
TI  - Effects of 24-hour blood pressure and heart rate recorded with ambulatory blood
      pressure monitoring on recovery from acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: This study used ambulatory blood pressure (BP) monitoring
      to generate BP and heart rate (HR) profiles soon after stroke onset and evaluated
      the association between determined values and 3-month stroke outcomes. METHODS:
      We analyzed 24-hour ambulatory BP monitoring records from 104 patients with acute
      ischemic stroke. Ambulatory BP monitoring was attached at the second and eighth
      hospitalization days (Days 1 and 7). Both BP and HR were characterized using
      baseline, mean, maximum, and minimum values and coefficient of variation during
      24-hour recording periods. Outcomes at 3 months were assessed as independence
      according to a modified Rankin Scale score of <=2 and poor according to the score
      of >=5. RESULTS: Sixty-six (63%) patients achieved independence and 12 (11%) had
      poor outcomes. Mean ambulatory BP monitoring values changed from 150.5+/
      19.5/85.7+/-11.3 mm Hg on Day 1 to 139.6+/-19.3/80.0+/-11.7 mm Hg on Day 7. After
      multivariate adjustment, mean values of systolic BP (OR, 0.63; 95% CI, 0.45
      0.85), diastolic BP (0.61; 0.37-0.98), pulse pressure (0.55; 0.33-0.85), and HR
      (0.61; 0.37-0.98) recorded on Day 1 as well as mean HR on Day 7 (0.47; 0.23-0.87)
      were inversely associated with independence and mean values of systolic BP (1.92;
      1.15-3.68), diastolic BP (5.28; 1.92-22.85), and HR (4.07; 1.83-11.88) on Day 1
      as well as mean HR on Day 7 (4.92; 1.36-36.99) were positively associated with a
      poor outcome. CONCLUSIONS: All of systolic BP, diastolic BP, pulse pressure, and
      HR on Day 1 and HR on Day 7 assessed using ambulatory BP monitoring were
      associated with outcomes of patients with stroke at 3 months.

PMID- 21960579
TI  - Crossed ataxia: a case report and a diffusion tensor imaging tractography study.
AB  - BACKGROUND AND PURPOSE: Ever since the seminal description of ataxic hemiparesis
      contralateral to a pontine lesion by Miller-Fisher, the question of why
      contralesional crossing pontocerebellar fibers do not more frequently produce
      ipsilesional hemiataxia was raised. The few cases of "quadrataxic hemiparesis" or
      bilateral leg ataxia remain exceptions. SUMMARY OF CASE: We report an even more
      unusual variant, namely "crossed ataxia" of the contralesional arm and the
      ipsilesional leg subsequent to an anteromedial pontine ischemic stroke.
      CONCLUSIONS: MRI diffusion tensor imaging tractography shows that caudal
      contralesional crossing pontocerebellar fibers (those for the leg) travel trough
      the lesion, whereas more rostral fibers (those for the arm) are spared.

PMID- 21960580
TI  - Body weight after stroke: lessons from the obesity paradox.
AB  - BACKGROUND AND PURPOSE: Outcome after acute stroke is determined to a large
      extent by poststroke complications. Nutritional status and metabolic balance may
      substantially contribute to outcome after stroke. Key mechanisms of stroke
      pathophysiology can induce systemic catabolic imbalance with impaired metabolic
      efficiency and degradation of body tissues. SUMMARY: Tissue wasting, sarcopenia,
      and cachexia may impair and delay poststroke rehabilitation and worsen the
      prognosis. Although current guidelines for secondary prevention after stroke
      recommend weight reduction, increasing evidence suggests that patients who are
      overweight and mildly obese may actually have a better outcome. An "obesity
      paradox" has been identified to describe the contrasting impact of being
      overweight in patients with chronic illness compared with healthy populations. We
      present an overview on the metabolic regulation in patients with stroke and
      evaluate current data on the impact of body weight and weight change after
      stroke. The emerging picture suggests that being overweight and obese may impact
      patients with stroke differently than it does healthy subjects. CONCLUSIONS: We
      propose that current knowledge on obesity and its management in primary
      prevention cannot be transferred to patients with established stroke. Systematic
      studies on changes in body composition after stroke and on treatment options are
      warranted to establish the pathophysiology and evidence-driven management of
      nutritional status in these patients.

PMID- 21960582
TI  - Validation of the Stroke Prognostic Instrument-II in a large, modern, community
      based cohort of ischemic stroke survivors.
AB  - BACKGROUND AND PURPOSE: The risk of recurrent stroke in the modern era of
      secondary stroke prevention is not well defined. Several prediction models,
      including the Stroke Prognostic Instrument-II (SPI-II), have been created to
      identify patients at highest risk, but their performance in modern populations
      has been infrequently tested. We aimed to assess the 1-year risk of recurrence
      after hospital discharge in a recent, large, community-based cohort of patients
      with ischemic stroke and to validate the SPI-II prediction model in this cohort.
      METHODS: From 2004 through 2006, 5575 patients with acute ischemic stroke were
      prospectively identified and followed for recurrent events. Kaplan-Meier
      statistics were used to analyze the cumulative incidence of recurrent ischemic
      stroke. Harrell c-statistic was calculated to determine the performance of SPI-II
      in predicting stroke or death at 1 year, and the log-rank test was used to
      compare the differences among low-, middle-, and high-risk groups. RESULTS: Among
      5575 patients with ischemic stroke, recurrence was observed in 221 during the
      subsequent year. Kaplan-Meier estimates of cumulative rates of recurrent stroke
      were 2.5%, 3.6%, and 4.8% at 3, 6, and 12 months, respectively. Rates of stroke
      or death for SPI-II in the low-, middle-, and high-risk groups were 8.2%, 24.5%,
      and 35.6%, respectively (trend, P=0.001). The c-statistic for SPI-II was 0.62
      (95% CI, 0.61-0.64). CONCLUSIONS: The modern 1-year rate of recurrent stroke
      after hospital discharge is low but still substantial at 4.8%. SPI-II is a
      modestly effective tool in identifying patients with ischemic stroke at highest
      risk of developing recurrence or death.

PMID- 21960581
TI  - Traditional risk factors as the underlying cause of racial disparities in stroke:
      lessons from the half-full (empty?) glass.
AB  - BACKGROUND AND PURPOSE: Black/white disparities in stroke incidence are well
      documented, but few studies have assessed the contributions to the disparity.
      Here we assess the contribution of "traditional" risk factors. METHODS: A total
      of 25 714 black and white men and women, aged>=45 years and stroke-free at
      baseline, were followed for an average of 4.4 years to detect stroke. Mediation
      analysis using proportional hazards analysis assessed the contribution of
      traditional risk factors to racial disparities. RESULTS: At age 45 years,
      incident stroke risk was 2.90 (95% CI: 1.72-4.89) times more likely in blacks
      than in whites and 1.66 (95% CI: 1.34-2.07) times at age 65 years. Adjustment for
      risk factors attenuated these excesses by 40% and 45%, respectively, resulting in
      relative risks of 2.14 (95% CI: 1.25-3.67) and 1.35 (95% CI: 1.08-1.71).
      Approximately one half of this mediation is attributable to systolic blood
      pressure. Further adjustment for socioeconomic factors resulted in total
      mediation of 47% and 53% to relative risks of 2.01 (95% CI: 1.16-3.47) and 1.30
      (1.03-1.65), respectively. CONCLUSIONS: Between ages 45 to 65 years,
      approximately half of the racial disparity in stroke risk is attributable to
      traditional risk factors (primarily systolic blood pressure) and socioeconomic
      factors, suggesting a critical need to understand the disparity in the
      development of these traditional risk factors. Because half of the excess stroke
      risk in blacks is not attributable to traditional risk factors and socioeconomic
      factors, differential impact of risk factors, residual confounding, or
      nontraditional risk factors may also play a role.

PMID- 21960583
TI  - The iScore predicts poor functional outcomes early after hospitalization for an
      acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: The iScore is a prediction tool originally developed to
      estimate the risk of death after hospitalization for an acute ischemic stroke.
      Our objective was to determine whether the iScore could also predict poor
      functional outcomes. METHODS: We applied the iScore to patients presenting with
      an acute ischemic stroke at multiple hospitals in Ontario, Canada, between 2003
      and 2008, who had been identified from the Registry of the Canadian Stroke
      Network regional stroke center database (n=3818) and from an external data set,
      the Registry of the Canadian Stroke Network Ontario Stroke Audit (n=4635).
      Patients were excluded if they were included in the sample used to develop and
      validate the initial iScore. Poor functional outcomes were defined as: (1) death
      at 30 days or disability at discharge, in which disability was defined as having
      a modified Rankin Scale 3 to 5; and (2) death at 30 days or institutionalization
      at discharge. RESULTS: The prevalence of poor functional outcomes in the Registry
      of the Canadian Stroke Network and the Ontario Stroke Audit, respectively, were
      55.7% and 44.1% for death at 30 days or disability at discharge and 16.9% and
      16.2%, respectively, for death at 30 days or institutionalization at discharge.
      The iScore stratified the risk of poor outcomes in low- and high-risk
      individuals. Observed versus predicted outcomes showed high correlations: 0.988
      and 0.940 for mortality or disability and 0.985 and 0.993 for mortality or
      institutionalization in the Registry of the Canadian Stroke Network and Ontario
      Stroke Audit cohorts. CONCLUSIONS: The iScore can be used to estimate the risk of
      death or a poor functional outcome after an acute ischemic stroke.

PMID- 21960584
TI  - Reduced efficacy of circulating costimulatory cells after focal cerebral
      ischemia.
AB  - BACKGROUND AND PURPOSE: Cerebral ischemia is ensued by a cellular immune
      depression syndrome. The postischemic functional capacity of T lymphocytes is
      controversial, and interactions between leukocyte subsets are largely unknown.
      Understanding the immunologic interplay between antigen-presenting cells and
      lymphocytes as well as between distinct lymphocyte subsets after stroke might be
      of clinical/therapeutic significance because animal data argue for a
      cerebroprotective effect of, for example, CD4+CD25+ regulatory T cells. METHODS:
      Ex vivo CD4+ T cell proliferation was analyzed in experimental and human stroke
      using fluorescence activated cell sorter analysis. To investigate suppressive
      effects of CD4+CD25+ regulatory T cells as well as the influence of costimulatory
      cells on CD4+ T cell proliferation, subsets were magnetically sorted before
      proliferation assay setup. RESULTS: After stroke: (1) proliferation of mouse and
      human CD4+ T cells on T cell receptor stimulation was unaltered; (2) the
      suppressive effect of CD4+CD25+ regulatory T cells in mouse and man was
      unaltered; and (3) efficacy of circulating costimulatory cells from stroke
      animals was reduced by a mean of 0.6 (SEM 0.1, P=0.001) CD4+ T cell division
      numbers compared with sham-treated animals. CONCLUSIONS: Reduced costimulatory
      efficacy of circulating costimulatory cells in mice is an important feature of
      stroke-induced immunodepression. Understanding the interplay of costimulatory
      cells and responder T cells (eg, CD4+ T cells or CD4+CD25+ regulatory T cells)
      after stroke may offer new insights into the prevention of secondary inflammatory
      damage to the brain and help to guide new therapeutic strategies.

PMID- 21960585
TI  - Low-dose intravenous recombinant tissue-type plasminogen activator therapy for
      patients with stroke outside European indications: Stroke Acute Management with
      Urgent Risk-factor Assessment and Improvement (SAMURAI) rtPA Registry.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to determine the safety and
      efficacy of intravenous recombinant tissue-type plasminogen activator (0.6 mg/kg
      alteplase) within 3 hours of stroke onset in Japanese patients outside the
      indications in the European license. METHODS: Of the 600 patients who were
      treated with recombinant tissue-type plasminogen activator, 422 met the inclusion
      criteria of the European license (IN group) and 178 did not (OUT group). RESULTS:
      The OUT group was inversely associated with any intracerebral hemorrhage
      (adjusted OR, 0.50; 95% CI, 0.29-0.84), positively associated with an unfavorable
      outcome (2.48; 1.55-3.94) and mortality (2.04; 1.02-4.04), and not associated
      with symptomatic intracerebral hemorrhage (0.53; 0.11-1.79) or complete
      independency (0.65; 0.40-1.03) after multivariate adjustment. CONCLUSIONS:
      Functional and vital outcomes 3 months after low-dose recombinant tissue-type
      plasminogen activator in patients outside the European indications were less
      favorable compared with those included in the indications; however, the risk of
      intracerebral hemorrhage was not.

PMID- 21960587
TI  - A distinctive form of immune thrombocytopenia in a phase 2 study of alemtuzumab
      for the treatment of relapsing-remitting multiple sclerosis.
AB  - In a phase 2 clinical trial of annual alemtuzumab for treatment of relapsing
      remitting multiple sclerosis, 6 of 216 patients (2.8%) developed immune
      thrombocytopenia (ITP). Over mean follow-up of 4.5 years, the incidence rate of
      ITP was 6.2 (95% confidence interval, 2.3-13.3) per 1000 person-years. Median
      times from initial and last alemtuzumab exposure to ITP diagnosis were 24.5 and
      10.5 months, respectively. Five patients developed severe thrombocytopenia. Four
      were symptomatic, including fatal intracranial hemorrhage in the index case. Four
      patients received standard first-line ITP therapy, all of whom responded to
      treatment within 1 week. All 5 surviving patients achieved complete remission and
      remained in complete remission without need for ongoing ITP therapy for a median
      duration of 34 months at last follow-up. A monitoring plan for the early
      detection of ITP, implemented after presentation of the index case, identified
      all 5 subsequent cases before serious hemorrhagic morbidity or mortality
      occurred. In conclusion, we describe a distinctive form of ITP associated with
      alemtuzumab treatment characterized by delayed presentation after drug exposure,
      responsiveness to conventional ITP therapies, and prolonged remission. Clinicians
      should maintain a high level of vigilance and consider routine monitoring for ITP
      in patients treated with this agent. This trial was registered at
      www.clinicaltrials.gov as #NCT00050778.

PMID- 21960586
TI  - SIV infection of rhesus macaques results in dysfunctional T- and B-cell responses
      to neo and recall Leishmania major vaccination.
AB  - HIV infection is characterized by immune system dysregulation, including
      depletion of CD4+ T cells, immune activation, and abnormal B- and T-cell
      responses. However, the immunologic mechanisms underlying lymphocytic
      dysfunctionality and whether it is restricted to immune responses against neo
      antigens, recall antigens, or both is unclear. Here, we immunized SIV-infected
      and uninfected rhesus macaques to induce immune responses against neo and recall
      antigens using a Leishmania major polyprotein (MML) vaccine given with poly-ICLC
      adjuvant. We found that vaccinated SIVuninfected animals induced high frequencies
      of polyfunctional MML-specific CD4+ T cells. However, in SIV-infected animals,
      CD4+ T-cell functionality decreased after both neo (P = .0025) and recall (P =
      .0080) MML vaccination. Furthermore, after SIV infection, the frequency of MML
      specific antibody-secreting classic memory B cells was decreased compared with
      vaccinated, SIV-uninfected animals. Specifically, antibody-secreting classic
      memory B cells that produced IgA in response to either neo (P = .0221) or recall
      (P = .0356) MML vaccinations were decreased. Furthermore, we found that T
      follicular helper cells, which are essential for priming B cells, are
      preferentially infected with SIV. These data indicate that SIV infection results
      in dysfunctional T-cell responses to neo and recall vaccinations, and direct SIV
      infection of T-follicular helper cells, both of which probably contribute to
      deficient B-cell responses and, presumably, susceptibility to certain
      opportunistic infections.

PMID- 21960588
TI  - The tolerogenic interplay(s) among HLA-G, myeloid APCs, and regulatory cells.
AB  - Myeloid antigen-presenting cells (APCs), regulatory cells, and the HLA-G molecule
      are involved in modulating immune responses and promoting tolerance. APCs are
      known to induce regulatory cells and to express HLA-G as well as 2 of its
      receptors; regulatory T cells can express and act through HLA-G; and HLA-G has
      been directly involved in the generation of regulatory cells. Thus, interplay(s)
      among HLA-G, APCs, and regulatory cells can be easily envisaged. However, despite
      a large body of evidence on the tolerogenic properties of HLA-G, APCs, and
      regulatory cells, little is known on how these tolerogenic players cooperate. In
      this review, we first focus on key aspects of the individual relationships
      between HLA-G, myeloid APCs, and regulatory cells. In its second part, we
      highlight recent work that gathers individual effects and demonstrates how
      intertwined the HLA-G/myeloid APCs/regulatory cell relationship is.

PMID- 21960589
TI  - Developmental origins and impact of BCR-ABL1 fusion and IKZF1 deletions in
      monozygotic twins with Ph+ acute lymphoblastic leukemia.
AB  - The timing and developmental sequence of events for BCR-ABL1(+) acute
      lymphoblastic leukemia (ALL), usually associated with IKAROS (IKZF1) deletions,
      are unknown. We assessed the status of BCR-ABL1 and IKZF1 genes in 2 pairs of
      monozygotic twins, one pair concordant, the other discordant for Philadelphia
      chromosome positive (Ph(+)) ALL. The twin pair concordant for ALL shared
      identical BCR-ABL1 genomic sequence indicative of monoclonal, in utero origin.
      One twin had IKZF1 deletion and died after transplantation. The other twin had
      hyperdiploidy, no IKZF1 deletion, and is still in remission 8 years after
      transplantation. In the twin pair discordant for ALL, neonatal blood spots from
      both twins harbored the same clonotypic BCR-ABL1 sequence. Low level BCR-ABL1(+)
      cells were present in the healthy co-twin but lacked the IKZF1 deletion present
      in the other twin's leukemic cells. The twin with ALL relapsed and died after
      transplantation. The co-twin remains healthy and leukemia free. These data show
      that in childhood Ph(+) ALL, BCR-ABL1 gene fusion can be a prenatal and possibly
      initiating genetic event. In the absence of additional, secondary changes, the
      leukemic clone remains clinically silent. IKZF1 is a secondary and probable
      postnatal mutation in these cases, and as a recurrent but alternative copy number
      change is associated with poor prognosis.

PMID- 21960590
TI  - Human microRNA-27a* targets Prf1 and GzmB expression to regulate NK-cell
      cytotoxicity.
AB  - Perforin (Prf1) and granzyme B (GzmB) are essential effector molecules for
      natural killer (NK)-cell cytotoxicity, but how Prf1 and GzmB expression is
      regulated during arming of NK cells is poorly defined. We show that human
      microRNA (miR)-27a* is a negative regulator of NK-cell cytotoxicity by silencing
      Prf1 and GzmB expression. Human miR-27a* specifically bound to the 3'
      untranslated regions of Prf1 and GzmB, down-regulating expression in both resting
      and activated NK cells, and it functioned as a fine-tuner for homeostasis of the
      net amount of the effector proteins. Consistent with miR-27a* having an
      inhibitory role, knockdown of miR-27a* in NK cells dramatically increased
      cytotoxicity in vitro and decreased tumor growth in a human tumor xenograft
      model. Thus, NK-cell cytotoxicity is regulated, in part, by microRNA, and
      modulating endogenous miR-27a* levels in NK cells represents a potential
      immunotherapeutic strategy.

PMID- 21960591
TI  - Prognostic DNA methylation patterns in cytogenetically normal acute myeloid
      leukemia are predefined by stem cell chromatin marks.
AB  - Cytogenetically normal acute myeloid leukemia (CN-AML) compose between 40% and
      50% of all adult acute myeloid leukemia (AML) cases. In this clinically diverse
      group, molecular aberrations, such as FLT3-ITD, NPM1, and CEBPA mutations,
      recently have added to the prognostic accuracy. Aberrant DNA methylation is a
      hallmark of cancer, including AML. We investigated in total 118 CN-AML samples in
      a test and a validation cohort for genome-wide promoter DNA methylation with
      Illumina Methylation Bead arrays and compared them with normal myeloid precursors
      and global gene expression. IDH and NPM1 mutations were associated with different
      methylation patterns (P = .0004 and .04, respectively). Genome-wide methylation
      levels were elevated in IDH-mutated samples (P = .006). We observed a negative
      impact of DNA methylation on transcription. Genes targeted by Polycomb group
      (PcG) proteins and genes associated with bivalent histone marks in stem cells
      showed increased aberrant methylation in AML (P < .0001). Furthermore, high
      methylation levels of PcG target genes were independently associated with better
      progression-free survival (odds ratio = 0.47, P = .01) and overall survival (odds
      ratio = 0.36, P = .001). In summary, genome-wide methylation patterns show
      preferential methylation of PcG targets with prognostic impact in CN-AML.

PMID- 21960594
TI  - Turkey and science academies.

PMID- 21960592
TI  - MicroRNA profiles of t(14;18)-negative follicular lymphoma support a late
      germinal center B-cell phenotype.
AB  - A total of 90% of follicular lymphomas (FLs) harbor the translocation t(14;18)
      leading to deregulated BCL2 expression. Conversely, 10% of FLs lack the t(14;18),
      and the majority of these FLs do not express BCL2. The molecular features of
      t(14;18)-negative FLs remain largely unknown. We performed microRNA expression
      analysis in 32 FL grades 1 to 3A, including 17 t(14;18)-positive FLs, 9 t(14;18)
      negative FLs without BCL2 expression, and 6 t(14;18)-negative FLs with BCL2
      expression. MicroRNA profiles were correlated with corresponding mRNA expression
      patterns, and potential targets were investigated by quantitative PCR and
      immunohistochemistry in an independent validation series of 83 FLs. Statistical
      analysis identified 17 microRNAs that were differentially expressed between
      t(14;18)-positive FLs and t(14;18)-negative FLs. The down-regulation of miR-16,
      miR-26a, miR-101, miR-29c, and miR138 in the t(14;18)-negative FL subset was
      associated with profound mRNA expression changes of potential target genes
      involving cell cycle control, apoptosis, and B-cell differentiation. miR-16
      target CHEK1 showed increased expression in t(14;18)-negative FLs, whereas TCL1A
      expression was reduced, in line with a partial loss of the germinal center B-cell
      phenotype in this FL subset. In conclusion, t(14;18)-negative FL have distinct
      microRNA profiles that are associated with an increased proliferative capacity
      and a "late" germinal center B-cell phenotype.

PMID- 21960593
TI  - Thrombocytopenia resulting from mutations in filamin A can be expressed as an
      isolated syndrome.
AB  - Filaminopathies A caused by mutations in the X-linked FLNA gene are responsible
      for a wide spectrum of rare diseases including 2 main phenotypes, the X-linked
      dominant form of periventricular nodular heterotopia (FLNA-PVNH) and the
      otopalatodigital syndrome spectrum of disorders. In platelets, filamin A (FLNa)
      tethers the principal receptors ensuring the platelet-vessel wall interaction,
      glycoprotein Ibalpha and integrin alphaIIbbeta3, to the underlying cytoskeleton.
      Hemorrhage, coagulopathy, and thrombocytopenia are mentioned in several reports
      on patients with FLNA-PVNH. Abnormal platelet morphology in 2 patients with FLNA
      PVNH prompted us to examine a third patient with similar platelet morphology
      previously diagnosed with immunologic thrombocytopenic purpura. Her enlarged
      platelets showed signs of FLNa degradation in Western blotting, and a
      heterozygous missense mutation in FLNA was detected. An irregular distribution of
      FLNa within the total platelet population was shown by confocal microscopy for
      all 3 patients. In vitro megakaryocyte cultures showed an abnormal
      differentiation, including an irregular distribution of FLNa with a frayed
      aspect, the presence of enlarged alpha-granules, and an abnormal fragmentation of
      the cytoplasm. Mutations in FLNA may represent an unrecognized cause of
      macrothrombocytopenia with an altered platelet production and a modified platelet
      vessel wall interaction.

PMID- 21960598
TI  - Special relativity. From Geneva to Italy faster than a speeding photon?

PMID- 21960599
TI  - Virology. The waning conflict over XMRV and chronic fatigue syndrome.

PMID- 21960600
TI  - Scientific workforce. NSF touts family-friendly policies as boon to women.

PMID- 21960601
TI  - Planetary science. Mercury looking less exotic, more a member of the family.

PMID- 21960602
TI  - Public health. Experts debate polypill: a single pill for global health.

PMID- 21960603
TI  - Sociology. Social scientists wade into the tweet stream.

PMID- 21960604
TI  - Neuroscience. Playing by ear.

PMID- 21960605
TI  - Epidemiology. Outbreak detectives embrace the genome era.

PMID- 21960606
TI  - Astronomy. First global telescope opens an eye on the cold universe.

PMID- 21960607
TI  - Retraction.

PMID- 21960608
TI  - Editor's note.

PMID- 21960609
TI  - Tiger conservation: trust tradition.

PMID- 21960610
TI  - The ant who learned to be an elephant.

PMID- 21960612
TI  - Comment on "The response of vegetation on the Andean flank in western Amazonia to
      Pleistocene climate change".
AB  - Cardenas et al. (Reports, 25 February 2011, p. 1055) used the presence of
      Podocarpus pollen and wood to infer >=5 degrees C cooling of Andean forests
      during Quaternary glacial periods. We show that (i) Podocarpus has a wide
      elevation range in the Neotropics, and (ii) edaphic factors cannot be discounted
      as a factor governing its distribution. Paleoecologists should therefore
      reevaluate Podocarpus as a cool-temperature proxy.

PMID- 21960614
TI  - Science and law. Rescuing wolves from politics: wildlife as a public trust
      resource.

PMID- 21960615
TI  - Cell biology. Sensing ER stress.

PMID- 21960616
TI  - Chemistry. Striking a balance to control stereochemistry.

PMID- 21960617
TI  - Planetary science. Sunshine on a cloudy forecast.

PMID- 21960618
TI  - Circadian rhythms. A new histone code for clocks?

PMID- 21960619
TI  - Materials science. Predicting the flow of real polymers.

PMID- 21960620
TI  - Retrospective. Bernadine Healy (1944-2011).

PMID- 21960621
TI  - SPORE series winner. Making Earth science data accessible and usable in
      education.

PMID- 21960622
TI  - TAL effectors: customizable proteins for DNA targeting.
AB  - Generating and applying new knowledge from the wealth of available genomic
      information is hindered, in part, by the difficulty of altering nucleotide
      sequences and expression of genes in living cells in a targeted fashion. Progress
      has been made in engineering DNA binding domains to direct proteins to particular
      sequences for mutagenesis or manipulation of transcription; however, achieving
      the requisite specificities has been challenging. Transcription activator-like
      (TAL) effectors of plant pathogenic bacteria contain a modular DNA binding domain
      that appears to overcome this challenge. Comprising tandem, polymorphic amino
      acid repeats that individually specify contiguous nucleotides in DNA, this domain
      is being deployed in DNA targeting for applications ranging from understanding
      gene function in model organisms to improving traits in crop plants to treating
      genetic disorders in people.

PMID- 21960623
TI  - The major-element composition of Mercury's surface from MESSENGER X-ray
      spectrometry.
AB  - X-ray fluorescence spectra obtained by the MESSENGER spacecraft orbiting Mercury
      indicate that the planet's surface differs in composition from those of other
      terrestrial planets. Relatively high Mg/Si and low Al/Si and Ca/Si ratios rule
      out a lunarlike feldspar-rich crust. The sulfur abundance is at least 10 times
      higher than that of the silicate portion of Earth or the Moon, and this
      observation, together with a low surface Fe abundance, supports the view that
      Mercury formed from highly reduced precursor materials, perhaps akin to enstatite
      chondrite meteorites or anhydrous cometary dust particles. Low Fe and Ti
      abundances do not support the proposal that opaque oxides of these elements
      contribute substantially to Mercury's low and variable surface reflectance.

PMID- 21960624
TI  - Radioactive elements on Mercury's surface from MESSENGER: implications for the
      planet's formation and evolution.
AB  - The MESSENGER Gamma-Ray Spectrometer measured the average surface abundances of
      the radioactive elements potassium (K, 1150 +/- 220 parts per million), thorium
      (Th, 220 +/- 60 parts per billion), and uranium (U, 90 +/- 20 parts per billion)
      in Mercury's northern hemisphere. The abundance of the moderately volatile
      element K, relative to Th and U, is inconsistent with physical models for the
      formation of Mercury requiring extreme heating of the planet or its precursor
      materials, and supports formation from volatile-containing material comparable to
      chondritic meteorites. Abundances of K, Th, and U indicate that internal heat
      production has declined substantially since Mercury's formation, consistent with
      widespread volcanism shortly after the end of late heavy bombardment 3.8 billion
      years ago and limited, isolated volcanic activity since.

PMID- 21960625
TI  - Flood volcanism in the northern high latitudes of Mercury revealed by MESSENGER.
AB  - MESSENGER observations from Mercury orbit reveal that a large contiguous expanse
      of smooth plains covers much of Mercury's high northern latitudes and occupies
      more than 6% of the planet's surface area. These plains are smooth, embay other
      landforms, are distinct in color, show several flow features, and partially or
      completely bury impact craters, the sizes of which indicate plains thicknesses of
      more than 1 kilometer and multiple phases of emplacement. These characteristics,
      as well as associated features, interpreted to have formed by thermal erosion,
      indicate emplacement in a flood-basalt style, consistent with x-ray spectrometric
      data indicating surface compositions intermediate between those of basalts and
      komatiites. The plains formed after the Caloris impact basin, confirming that
      volcanism was a globally extensive process in Mercury's post-heavy bombardment
      era.

PMID- 21960626
TI  - Hollows on Mercury: MESSENGER evidence for geologically recent volatile-related
      activity.
AB  - High-resolution images of Mercury's surface from orbit reveal that many bright
      deposits within impact craters exhibit fresh-appearing, irregular, shallow,
      rimless depressions. The depressions, or hollows, range from tens of meters to a
      few kilometers across, and many have high-reflectance interiors and halos. The
      host rocks, which are associated with crater central peaks, peak rings, floors,
      and walls, are interpreted to have been excavated from depth by the crater
      forming process. The most likely formation mechanisms for the hollows involve
      recent loss of volatiles through some combination of sublimation, space
      weathering, outgassing, or pyroclastic volcanism. These features support the
      inference that Mercury's interior contains higher abundances of volatile
      materials than predicted by most scenarios for the formation of the solar
      system's innermost planet.

PMID- 21960627
TI  - The global magnetic field of Mercury from MESSENGER orbital observations.
AB  - Magnetometer data acquired by the MESSENGER spacecraft in orbit about Mercury
      permit the separation of internal and external magnetic field contributions. The
      global planetary field is represented as a southward-directed, spin-aligned,
      offset dipole centered on the spin axis. Positions where the cylindrical radial
      magnetic field component vanishes were used to map the magnetic equator and
      reveal an offset of 484 +/- 11 kilometers northward of the geographic equator.
      The magnetic axis is tilted by less than 3 degrees  from the rotation axis. A
      magnetopause and tail-current model was defined by using 332 magnetopause
      crossing locations. Residuals of the net external and offset-dipole fields from
      observations north of 30 degrees N yield a best-fit planetary moment of 195 +/-
      10 nanotesla-R(M)(3), where R(M) is Mercury's mean radius.

PMID- 21960628
TI  - MESSENGER observations of the spatial distribution of planetary ions near
      Mercury.
AB  - Global measurements by MESSENGER of the fluxes of heavy ions at Mercury,
      particularly sodium (Na(+)) and oxygen (O(+)), exhibit distinct maxima in the
      northern magnetic-cusp region, indicating that polar regions are important
      sources of Mercury's ionized exosphere, presumably through solar-wind sputtering
      near the poles. The observed fluxes of helium (He(+)) are more evenly
      distributed, indicating a more uniform source such as that expected from
      evaporation from a helium-saturated surface. In some regions near Mercury,
      especially the nightside equatorial region, the Na(+) pressure can be a
      substantial fraction of the proton pressure.

PMID- 21960629
TI  - MESSENGER observations of transient bursts of energetic electrons in Mercury's
      magnetosphere.
AB  - The MESSENGER spacecraft began detecting energetic electrons with energies
      greater than 30 kilo-electron volts (keV) shortly after its insertion into orbit
      about Mercury. In contrast, no energetic protons were observed. The energetic
      electrons arrive as bursts lasting from seconds to hours and are most intense
      close to the planet, distributed in latitude from the equator to the north pole,
      and present at most local times. Energies can exceed 200 keV but often exhibit
      cutoffs near 100 keV. Angular distributions of the electrons about the magnetic
      field suggest that they do not execute complete drift paths around the planet.
      This set of characteristics demonstrates that Mercury's weak magnetic field does
      not support Van Allen-type radiation belts, unlike all other planets in the solar
      system with internal magnetic fields.

PMID- 21960630
TI  - Evidence of water vapor in excess of saturation in the atmosphere of Mars.
AB  - The vertical distribution of water vapor is key to the study of Mars'
      hydrological cycle. To date, it has been explored mainly through global climate
      models because of a lack of direct measurements. However, these models assume the
      absence of supersaturation in the atmosphere of Mars. Here, we report
      observations made using the SPICAM (Spectroscopy for the Investigation of the
      Characteristics of the Atmosphere of Mars) instrument onboard Mars Express that
      provide evidence of the frequent presence of water vapor in excess of saturation,
      by an amount far surpassing that encountered in Earth's atmosphere. This result
      contradicts the widespread assumption that atmospheric water on Mars cannot exist
      in a supersaturated state, directly affecting our long-term representation of
      water transport, accumulation, escape, and chemistry on a global scale.

PMID- 21960631
TI  - Linking models of polymerization and dynamics to predict branched polymer
      structure and flow.
AB  - We present a predictive scheme connecting the topological structure of highly
      branched entangled polymers, with industrial-level complexity, to the emergent
      viscoelasticity of the polymer melt. The scheme is able to calculate the linear
      and nonlinear viscoelasticity of a stochastically branched "high-pressure free
      radical" polymer melt as a function of the chemical kinetics of its formation.
      The method combines numerical simulation of polymerization with the
      tube/entanglement physics of polymer dynamics extended to fully nonlinear
      response. We compare calculations for a series of low-density polyethylenes with
      experiments on structural and viscoelastic properties. The method provides a
      window onto the molecular processes responsible for the optimized rheology of
      these melts, connecting fundamental science to process in complex flow, and opens
      up the in silico design of new materials.

PMID- 21960632
TI  - Three-dimensional correlation of steric and electronic free energy relationships
      guides asymmetric propargylation.
AB  - Chemical reaction outcomes are often rationalized on the basis of independent
      analyses of steric and electronic effects. We applied three-dimensional free
      energy relationships correlating steric and electronic effects to design and
      optimize a ligand class for the enantioselective Nozaki-Hiyama-Kishi
      propargylation of ketones. The resultant mathematical model describing the steric
      and electronic parameter relationship is highly reliant on the synergistic
      interactions of these two effects.

PMID- 21960633
TI  - Diurnal and seasonal mood vary with work, sleep, and daylength across diverse
      cultures.
AB  - We identified individual-level diurnal and seasonal mood rhythms in cultures
      across the globe, using data from millions of public Twitter messages. We found
      that individuals awaken in a good mood that deteriorates as the day progresses-
      which is consistent with the effects of sleep and circadian rhythm--and that
      seasonal change in baseline positive affect varies with change in daylength.
      People are happier on weekends, but the morning peak in positive affect is
      delayed by 2 hours, which suggests that people awaken later on weekends.

PMID- 21960634
TI  - Histone lysine demethylase JARID1a activates CLOCK-BMAL1 and influences the
      circadian clock.
AB  - In animals, circadian oscillators are based on a transcription-translation
      circuit that revolves around the transcription factors CLOCK and BMAL1. We found
      that the JumonjiC (JmjC) and ARID domain-containing histone lysine demethylase 1a
      (JARID1a) formed a complex with CLOCK-BMAL1, which was recruited to the Per2
      promoter. JARID1a increased histone acetylation by inhibiting histone deacetylase
      1 function and enhanced transcription by CLOCK-BMAL1 in a demethylase-independent
      manner. Depletion of JARID1a in mammalian cells reduced Per promoter histone
      acetylation, dampened expression of canonical circadian genes, and shortened the
      period of circadian rhythms. Drosophila lines with reduced expression of the
      Jarid1a homolog, lid, had lowered Per expression and similarly altered circadian
      rhythms. JARID1a thus has a nonredundant role in circadian oscillator function.

PMID- 21960635
TI  - Superfast muscles set maximum call rate in echolocating bats.
AB  - As an echolocating bat closes in on a flying insect, it increases call emission
      to rates beyond 160 calls per second. This high call rate phase, dubbed the
      terminal buzz, has proven enigmatic because it is unknown how bats are able to
      produce calls so quickly. We found that previously unknown and highly specialized
      superfast muscles power rapid call rates in the terminal buzz. Additionally, we
      show that laryngeal motor performance, not overlap between call production and
      the arrival of echoes at the bat's ears, limits maximum call rate. Superfast
      muscles are rare in vertebrates and always associated with extraordinary motor
      demands on acoustic communication. We propose that the advantages of rapid
      auditory updates on prey movement selected for superfast laryngeal muscle in
      echolocating bats.

PMID- 21960636
TI  - Chromosome segregation errors as a cause of DNA damage and structural chromosome
      aberrations.
AB  - Various types of chromosomal aberrations, including numerical (aneuploidy) and
      structural (e.g., translocations, deletions), are commonly found in human tumors
      and are linked to tumorigenesis. Aneuploidy is a direct consequence of chromosome
      segregation errors in mitosis, whereas structural aberrations are caused by
      improperly repaired DNA breaks. Here, we demonstrate that chromosome segregation
      errors can also result in structural chromosome aberrations. Chromosomes that
      missegregate are frequently damaged during cytokinesis, triggering a DNA double
      strand break response in the respective daughter cells involving ATM, Chk2, and
      p53. We show that these double-strand breaks can lead to unbalanced
      translocations in the daughter cells. Our data show that segregation errors can
      cause translocations and provide insights into the role of whole-chromosome
      instability in tumorigenesis.

PMID- 21960638
TI  - Aesthetic outcomes of labioplasty.

PMID- 21960637
TI  - GRK2-dependent S1PR1 desensitization is required for lymphocytes to overcome
      their attraction to blood.
AB  - Lymphocytes egress from lymphoid organs in response to sphingosine-1-phosphate
      (S1P); minutes later they migrate from blood into tissue against the S1P
      gradient. The mechanisms facilitating cell movement against the gradient have not
      been defined. Here, we show that heterotrimeric guanine nucleotide-binding
      protein-coupled receptor kinase-2 (GRK2) functions in down-regulation of S1P
      receptor-1 (S1PR1) on blood-exposed lymphocytes. T and B cell movement from blood
      into lymph nodes is reduced in the absence of GRK2 but is restored in S1P
      deficient mice. In the spleen, B cell movement between the blood-rich marginal
      zone and follicles is disrupted by GRK2 deficiency and by mutation of an S1PR1
      desensitization motif. Moreover, delivery of systemic antigen into follicles is
      impaired. Thus, GRK2-dependent S1PR1 desensitization allows lymphocytes to escape
      circulatory fluids and migrate into lymphoid tissues.

PMID- 21960640
TI  - Muller glia, vision-guided ocular growth, retinal stem cells, and a little
      serendipity: the Cogan lecture.
AB  - Hypothesis-driven science is expected to result in a continuum of studies and
      findings along a discrete path. By comparison, serendipity can lead to new
      directions that branch into different paths. Herein, I describe a diverse series
      of findings that were motivated by hypotheses, but driven by serendipity. I
      summarize how investigations into vision-guided ocular growth in the chick eye
      led to the identification of glucagonergic amacrine cells as key regulators of
      ocular elongation. Studies designed to assess the impact of the ablation of
      different types of neurons on vision-guided ocular growth led to the finding of
      numerous proliferating cells within damaged retinas. These proliferating cells
      were Muller glia-derived retinal progenitors with a capacity to produce new
      neurons. Studies designed to investigate Muller glia-derived progenitors led to
      the identification of a domain of neural stem cells that form a circumferential
      marginal zone (CMZ) that lines the periphery of the retina. Accelerated ocular
      growth, caused by visual deprivation, stimulated the proliferation of CMZ
      progenitors. We formulated a hypothesis that growth-regulating glucagonergic
      cells may regulate both overall eye size (scleral growth) and the growth of the
      retina (proliferation of CMZ cells). Subsequent studies identified unusual types
      of glucagonergic neurons with terminals that ramify within the CMZ; these cells
      use visual cues to control equatorial ocular growth and the proliferation of CMZ
      cells. Finally, while studying the signaling pathways that stimulate CMZ and
      Muller glia-derived progenitors, serendipity led to the discovery of a novel type
      of glial cell that is scattered across the inner retinal layers.

PMID- 21960642
TI  - Why HLA-B27? My thirty-year quest: the Friedenwald lecture.

PMID- 21960644
TI  - Reflections on "hot" blind spots: lessons from research on aging macula disorder
      and glaucoma: the Weisenfeld lecture.

PMID- 21960646
TI  - Commentary: Persistent gaps in VTE prophylaxis in orthopedic surgery: will new
      educational strategies help?

PMID- 21960645
TI  - Current gene discovery strategies for ocular conditions.

PMID- 21960647
TI  - Improving awareness of best practices to reduce surgical site infection: a
      multistakeholder approach.
AB  - Surgical site infection (SSI) is recognized as a focus area by the Centers for
      Medicare and Medicaid Services, the Joint Commission, the Institute for
      Healthcare Improvement, and the Institute of Medicine. An estimated 47% to 84% of
      SSIs present after discharge from the hospital or ambulatory care facility and,
      as a result, go undetected by standard SSI surveillance programs. Evidence-based
      processes and practices that are known to reduce the incidence of SSIs tend to be
      underused in routine practice. This article describes a multistakeholder process
      used to develop an educational initiative to raise awareness of best practices to
      reduce SSIs. The goal was to create a patient-centric educational initiative that
      involved an active partnership among all stakeholders-medical professional
      organizations, hospitals/health systems, health insurers, employers and other
      purchasers, and consumers/patients-to provide the climate necessary to create and
      sustain a culture of safety.

PMID- 21960648
TI  - Prevalence of trigeminal neuralgia and persistent idiopathic facial pain: a
      population-based study.
AB  - OBJECTIVE: To estimate the lifetime prevalence of trigeminal neuralgia (TN) and
      persistent idiopathic facial pain (PIFP) in a population-based sample in Germany.
      METHODS: A total of 3336 responders of 6000 contacted inhabitants of the city of
      Essen in Germany were screened using a self-assessment questionnaire. 327
      individuals, who reported recurrent facial pain and randomly selected 150 (5% of
      3009) screening negative subjects, received a phone interview by one of six
      neurologists and if necessary a face-to-face examination. Those with suspected TN
      or PIFP following the phone interview underwent neurological examination by two
      neurologists who were unaware of the presumed diagnosis. A random group of 25
      (10% of 247) phone interview negative subjects was examined face-to-face. All
      suspected cases of PIFP received otorhinolaryngological examination and
      diagnostic cranial magnetic resonance imaging (MRI). In TN patients the number of
      vessel-nerve contacts was determined by thin-slice cranial MRI. RESULTS: Lifetime
      prevalence of TN was estimated to be 0.3% [10 of 3336; 95% CI 0.1-0.5%], of PIFP
      0.03% [1 of 3336; 95% CI < 0.08%]. Thin-slice cranial MRI detected five vessel
      nerve contacts and no symptomatic lesions in the 10 TN patients. CONCLUSIONS:
      This large population-based study revealed that TN and PIFP are rare facial pain
      disorders.

PMID- 21960649
TI  - Primary headache syndromes in systemic mastocytosis.
AB  - AIM: To investigate the relationship between clinical mast cell activity and
      primary headache syndromes. METHODS: We surveyed individuals with systemic
      mastocytosis, an uncommon disorder associated with increased mast cell activity.
      Diagnoses of primary headache syndromes in addition to the relationship of
      headache and symptoms of mastocytosis were ascertained. RESULTS: A response rate
      of 64/148 (43.2%) was achieved. Headache diagnoses in our respondents (n = 64)
      were largely migraine (37.5%) and tension-type headaches (17.2%). Typical aura
      with and without migraine headache was highly represented in our patient
      population (n = 25, 39%). Three individuals met criteria for primary cough
      headache (4.7%). Symptoms reflective of mast cell activity were significantly
      greater in individuals reporting headaches. Patients experiencing headache
      concurrently with mastocytosis flairs were more likely to be male (p = 0.002),
      have histaminergic symptoms, such as itching (p = 0.02) and runny nose (p =
      0.03), and have unilateral cranial autonomic features (p = 0.04). However, using
      standardized International Headache Society criteria, we did not identify
      individuals with cluster headache or other trigeminal autonomic cephalalgias in
      this population. CONCLUSIONS: Our observational survey-based data supports a
      clinical relationship between mast cell activity and primary headache syndromes.
      Generalizability of our results is limited by the low response rate and possible
      tertiary referral bias.

PMID- 21960650
TI  - New daily persistent headache: should migrainous features be incorporated?
AB  - INTRODUCTION: International Classification of Headache Disorders (ICHD-2)
      criteria for new daily persistent headache (NDPH) require tension-type headache
      features. Many patients with 'new-onset persistent' headache fail to fulfil such
      criteria due to prominent migrainous features. SUBJECTS AND METHODS: We reviewed
      all NDPH patients in our headache clinic, using the definition of persistent
      headache < 3 days after onset for > 3 months. The patients were dichotomised:
      patients meeting ICHD-2 criteria (NDPH-S) and patients failing to meet ICHD-2
      criteria due to prominent migrainous features (NDPH-M). All patients had
      completed a structured intake form including demographics, headache profiles,
      Beck Depression Inventory (BDI), Short Form 36 (SF-36) Health Survey, and
      Migraine Disability Assessment (MIDAS). A telephone interview was conducted for
      follow-up. RESULTS: A total of 92 NDPH patients were enrolled (59 (64.1%) NDPH-M,
      33 (35.9%) NDPH-S). Between the two subgroups, the sociodemographics were
      indistinguishable, but the patients with NDPH-M had higher headache intensity,
      BDI scores, MIDAS scores, and lower scores of most SF-36 subscales. After an
      average of 2 years of follow-up, 57 (66%) had a good outcome (>= 50% reduction in
      headache frequency). Cox proportional analysis showed that disease duration <= 6
      months and NDPH-S diagnosis predicted good outcomes. CONCLUSION: Migrainous
      features were common in patients with NDPH. Unlike prior studies, our study
      showed NDPH-M represented a more severe subgroup with a poorer outcome compared
      with NDPH-S.

PMID- 21960651
TI  - Apolipoprotein B, oxidized low-density lipoprotein, and LDL particle size in
      predicting the incidence of metabolic syndrome: the Cardiovascular Risk in Young
      Finns study.
AB  - OBJECTIVE: To test whether serum apolipoprotein B (apoB) and low-density
      lipoprotein (LDL) particle characteristics (oxidation and mean particle size)
      predict the incidence of metabolic syndrome (MetS). METHODS: The 6-year follow-up
      study included 1429 adults (baseline mean age 31.5). Lipids, apoB, and apoA1 were
      measured at baseline in 2001. LDL oxidation was measured with monoclonal antibody
      based enzyme-linked immunosorbent assay (oxLDL-prot) and with a method measuring
      oxidized lipids in LDL (oxLDL-lipids). Mean LDL particle size was calculated from
      proton nuclear magnetic resonance spectroscopy data. RESULTS: Increased
      concentrations of both oxLDL-measures were associated with increased apoB levels
      but not with LDL particle size. The odds ratios (95% confidence intervals) for
      MetS incidence during a 6-year follow up by quartiles of apoB were 2.0 (1.0-3.8)
      for the second quartile, 3.1 (1.7-5.7) for the third quartile, and 4.2 (2.3-7.6)
      for the fourth quartile. This association remained after adjusting for age, sex,
      body mass index, homeostasis model assessment for insulin resistance, C-reactive
      protein, smoking, LDL cholesterol, oxidized LDL measures (p <= 0.01) in addition
      to risk factors comprising the MetS (p = 0.03). OxLDL-prot and oxLDL-lipids
      levels were not independently associated with incident MetS after adjusting for
      apoB. Mean LDL particle size was not associated with the incidence of MetS.
      CONCLUSION: ApoB is associated with increased risk of MetS incidence. We found no
      clear evidence to suggest that increased LDL oxidation or small mean LDL particle
      size would facilitate the development of MetS.

PMID- 21960652
TI  - Serum homocysteine and folate but not vitamin B12 are predictors of CHD mortality
      in older adults.
AB  - AIMS: The associations of serum levels of homocysteine (tHcy), vitamin B(12), and
      folate with risk of all-cause and coronary heat disease (CHD) mortality is
      controversial, and the evidence in older adults is limited. The aim of this study
      was to examine whether serum folate, vitamin B(12), and tHcy independently
      predict risk of CHD-related and all-cause mortality in older adults. METHODS AND
      RESULTS: Serum concentrations of folate, vitamin B(12), and tHcy were determined
      from blood samples obtained from 3010 Blue Mountains Eye Study participants (1997
      99), aged >=55 years. CHD and all-cause mortality was confirmed using the
      Australian National Death Index. RESULTS: Persons in the highest quartile of
      serum tHcy had increased risk of CHD mortality compared to those in the lowest
      quartile (multivariable-adjusted hazard ratio, HR, 2.45, 95% CI 1.30-4.62). A
      significant continuous association was observed between serum tHcy and CHD
      mortality (HR per SD ( = 4.8 umol/l) increase in serum tHcy 1.25, 95% CI 1.08
      1.45), after multivariable-adjustment. A significant association between folate
      deficiency and CHD-mortality was found (multivariable-adjusted HR 1.53, 95% CI
      1.01-2.29). Hyperhomocysteinaemia (>15 umol/l) was a significant predictor of all
      cause mortality (multivariable-adjusted HR 1.47, 95% CI 1.18-1.83). A significant
      interaction was observed between hyperhomocysteinaemia and folate deficiency for
      all-cause and CHD mortality (p for interaction = 0.03 and p for interaction =
      0.05, respectively). CONCLUSION: Serum tHcy and folate were independent
      predictors of CHD and all-cause mortality, while vitamin B(12) was not
      associated. As raised tHcy levels and folate deficiency are associated with
      poorer lifestyle, changes to a more healthful lifestyle among older adults may
      minimize the adverse vascular effects of elevated tHcy.

PMID- 21960653
TI  - Short-term effect of motivational interviewing on clinical and psychological
      outcomes and health-related quality of life in cardiac rehabilitation patients
      with poor motivation in Hong Kong: a randomized controlled trial.
AB  - BACKGROUND: Motivational interviewing (MI) is effective in promoting behavioural
      changes in patients with substance abuse and smoking. However, its effectiveness
      on health outcomes in cardiac rehabilitation patients is unclear. DESIGN: A
      randomized controlled trial. METHOD: A total of 146 patients assessed as having
      poor motivation attended a cardiac rehabilitation programme from February 2008 to
      June 2010. Patients (n = 73) in the control group received usual care while those
      in the experimental group (n = 73) received usual care plus four sessions of MI,
      each lasting 30-45 min. Clinical and psychological outcomes and health-related
      quality of life were measured at baseline and 3 months after entering the
      programme. Descriptive statistics, independent t-test, Pearson Chi-squared test,
      and generalized estimating equations models were used to analyse the data.
      RESULTS: There was no significant difference between the two groups on clinical
      outcomes (all p-values >0.05). Patients in the experimental group had higher
      increases in health-related quality of life (SF-36) scores in the aspects of
      general health (4.74, 95% CI 0.04-9.44; p = 0.048) and role limitation due to
      emotional problems (8.80, 95% CI 1.16-16.43; p = 0.024). However, they reported
      significantly higher increases in anxiety levels (Hospital Anxiety and Depression
      Scale) than those in the control group (0.96, 95% CI 0.09-1.83; p = 0.030).
      CONCLUSION: The short-term effectiveness of MI on clinical outcomes and health
      related quality of life in poorly motivated cardiac rehabilitation patients is
      limited. MI, however, was shown to increase anxiety levels of patients during the
      study period (3 months). More evidence is needed to better understand this
      phenomenon in the future studies.

PMID- 21960654
TI  - Regional lung perfusion estimated by electrical impedance tomography in a piglet
      model of lung collapse.
AB  - The assessment of the regional match between alveolar ventilation and perfusion
      in critically ill patients requires simultaneous measurements of both parameters.
      Ideally, assessment of lung perfusion should be performed in real-time with an
      imaging technology that provides, through fast acquisition of sequential images,
      information about the regional dynamics or regional kinetics of an appropriate
      tracer. We present a novel electrical impedance tomography (EIT)-based method
      that quantitatively estimates regional lung perfusion based on first-pass
      kinetics of a bolus of hypertonic saline contrast. Pulmonary blood flow was
      measured in six piglets during control and unilateral or bilateral lung collapse
      conditions. The first-pass kinetics method showed good agreement with the
      estimates obtained by single-photon-emission computerized tomography (SPECT). The
      mean difference (SPECT minus EIT) between fractional blood flow to lung areas
      suffering atelectasis was -0.6%, with a SD of 2.9%. This method outperformed the
      estimates of lung perfusion based on impedance pulsatility. In conclusion, we
      describe a novel method based on EIT for estimating regional lung perfusion at
      the bedside. In both healthy and injured lung conditions, the distribution of
      pulmonary blood flow as assessed by EIT agreed well with the one obtained by
      SPECT. The method proposed in this study has the potential to contribute to a
      better understanding of the behavior of regional perfusion under different lung
      and therapeutic conditions.

PMID- 21960655
TI  - Ascorbic acid: what do we really no?

PMID- 21960656
TI  - Aging, visual information, and adaptation to task asymmetry in bimanual force
      coordination.
AB  - This study investigated the coordination and control strategies that the elderly
      adopt during a redundant finger force coordination task and how the amount of
      visual information regulates the coordination patterns. Three age groups (20-24,
      65-69, and 75-79 yr) performed a bimanual asymmetric force task. Task asymmetry
      was manipulated via imposing different coefficients on the finger forces such
      that the weighted sum of the two index finger forces equaled the total force. The
      amount of visual information was manipulated by changing the visual information
      gain of the total force output. Two hypotheses were tested: the reduced
      adaptability hypothesis predicts that the elderly show less degree of force
      asymmetry between hands compared with young adults in the asymmetric coefficient
      conditions, whereas the compensatory hypothesis predicts that the elderly exhibit
      more asymmetric force coordination patterns with asymmetric coefficients. Under
      the compensatory hypothesis, two contrasting directions of force sharing
      strategies (i.e., more efficient coordination strategy and minimum variance
      strategy) are expected. A deteriorated task performance (high performance error
      and force variability) was found in the two elderly groups, but enhanced visual
      information improved the task performance in all age groups. With low visual
      information gain, the elderly showed reduced adaptability (i.e., less asymmetric
      forces between hands) to the unequal weighting coefficients, which supported the
      reduced adaptability hypothesis; however, the elderly revealed the same degree of
      adaptation as the young group under high visual gain. The findings are consistent
      with the notion that the age-related reorganization of force coordination and
      control patterns is mediated by visual information and, more generally, the
      interactive influence of multiple categories of constraints.

PMID- 21960657
TI  - Pulse arrival time is not an adequate surrogate for pulse transit time as a
      marker of blood pressure.
AB  - Pulse transit time (PTT) is a proven, simple to measure, marker of blood pressure
      (BP) that could potentially permit continuous, noninvasive, and cuff-less BP
      monitoring (after an initial calibration). However, pulse arrival time (PAT),
      which is equal to the sum of PTT and the pre-ejection period, is gaining
      popularity for BP tracking, because it is even simpler to measure. The aim of
      this study was to evaluate the hypothesis that PAT is an adequate surrogate for
      PTT as a marker of BP. PAT and PTT were estimated through the aorta using high
      fidelity invasive arterial waveforms obtained from six dogs during wide BP
      changes induced by multiple interventions. These time delays and their
      reciprocals were evaluated in terms of their ability to predict diastolic, mean,
      and systolic BP (DBP, MBP, and SBP) per animal. The root mean squared error
      (RMSE) between the BP parameter predicted via the time delay and the measured BP
      parameter was specifically used as the evaluation metric. Taking the reciprocals
      of the time delays tended to reduce the RMSE values. The DBP, MBP, and SBP RMSE
      values for 1/PAT were 9.8 +/- 5.2, 10.4 +/- 5.6, and 11.9 +/- 6.1 mmHg, whereas
      the corresponding values for 1/PTT were 5.3 +/- 1.2, 4.8 +/- 1.0, and 7.5 +/- 2.2
      mmHg (P < 0.05). Thus tracking BP via PAT was not only markedly worse than via
      PTT but also unable to meet the FDA BP error limits. In contrast to previous
      studies, our results quantitatively indicate that PAT is not an adequate
      surrogate for PTT in terms of detecting challenging BP changes.

PMID- 21960658
TI  - Brief daily exposure to low-intensity vibration mitigates the degradation of the
      intervertebral disc in a frequency-specific manner.
AB  - Hindlimb unloading of the rat causes rapid hypotrophy of the intervertebral disc
      (IVD) as well as reduced IVD height and glycosaminoglycan content. Here we tested
      the hypothesis that low-intensity mechanical vibrations (0.2 g), as a surrogate
      for exercise, will mitigate this degradation. Four groups of Sprague-Dawley rats
      (4.5 mo, n = 11/group) were hindlimb unloaded (HU) for 4 wk. In two of the HU
      groups, unloading was interrupted for 15 min/day by placing rats in an upright
      posture on a platform that was vertically oscillating at 45 or 90 Hz (HU+45,
      HU+90). Sham control rats stood upright on an inactive plate for 15 min/day
      (HU+SC). These three experimental groups were compared with HU uninterrupted by
      weightbearing (HU) and to normally ambulating age-matched controls. In the HU and
      HU+SC rats, 4 wk of unloading resulted in a 10% smaller IVD height, as well as
      less glycosaminoglycan in the whole IVD (7%) and nucleus pulposus (17%) and a
      greater collagen-to-glycosaminoglycan ratio in the whole IVD (17%). Brief daily
      exposure to 90 Hz mechanical oscillations mitigated this degradation; compared
      with HU +/- SC, the IVD of HU+90 had an 8% larger height and greater
      glycosaminoglycan content in the whole IVD (12%) and nucleus pulposus (24%). In
      contrast, the 45 Hz signal failed to mitigate changes in height or
      glycosaminoglycan content brought with altered spinal loading, but normalized the
      collagen-to-glycosaminoglycan ratio to levels observed in age-matched controls.
      In summary, unloading caused marked phenotypic and biochemical changes in the
      IVD, a deterioration that was not slowed by brief weightbearing. However, low
      intensity 90 Hz vibrations superimposed on weightbearing largely preserved the
      morphology and biochemistry of the IVD and suggest that these biomechanically
      based signals may help protect the IVD during long bouts of nonambulation.

PMID- 21960659
TI  - Adaptive strength gains in dystrophic muscle exposed to repeated bouts of
      eccentric contraction.
AB  - The objective of this study was to determine the functional recovery and
      adaptation of dystrophic muscle to multiple bouts of contraction-induced injury.
      Because lengthening (i.e., eccentric) contractions are extremely injurious for
      dystrophic muscle, it was considered that repeated bouts of such contractions
      would exacerbate the disease phenotype in mdx mice. Anterior crural muscles
      (tibialis anterior and extensor digitorum longus) and posterior crural muscles
      (gastrocnemius, soleus, and plantaris) from mdx mice performed one or five
      repeated bouts of 100 electrically stimulated eccentric contractions in vivo, and
      each bout was separated by 10-18 days. Functional recovery from one bout was
      achieved 7 days after injury, which was in contrast to a group of wild-type mice,
      which still showed a 25% decrement in electrically stimulated isometric torque at
      that time point. Across bouts there was no difference in the immediate loss of
      strength after repeated bouts of eccentric contractions for mdx mice (-70%, P =
      0.68). However, after recovery from each bout, dystrophic muscle had greater
      torque-generating capacity such that isometric torque was increased ~38% for both
      anterior and posterior crural muscles at bout 5 compared with bout 1 (P < 0.001).
      Moreover, isolated extensor digitorum longus muscles excised from in vivo-tested
      hindlimbs 14-18 days after bout 5 had greater specific force than contralateral
      control muscles (12.2 vs. 10.4 N/cm(2), P = 0.005) and a 20% greater maximal
      relaxation rate (P = 0.049). Additional adaptations due to the multiple bouts of
      eccentric contractions included rapid recovery and/or sparing of contractile
      proteins, enhanced parvalbumin expression, and a decrease in fiber size
      variability. In conclusion, eccentric contractions are injurious to dystrophic
      skeletal muscle; however, the muscle recovers function rapidly and adapts to
      repeated bouts of eccentric contractions by improving strength.

PMID- 21960660
TI  - Microparticle enlargement and altered surface proteins after air decompression
      are associated with inflammatory vascular injuries.
AB  - Studies in a murine model have shown that decompression stress triggers a
      progressive elevation in the number of circulating annexin V-coated
      microparticles derived from leukocytes, erythrocytes, platelets, and endothelial
      cells. We noted that some particles appeared to be larger than anticipated, and
      size continued to increase for >=24 h postdecompression. These observations led
      to the hypothesis that inert gas bubbles caused the enlargement and particle size
      could be reduced by hydrostatic pressure. After demonstrating pressure-induced
      particle size reduction, we hypothesized that annexin V-positive particle changes
      associated with decompression contributed to their proinflammatory potential.
      Intravenous injection of naive mice with particles isolated from decompressed
      mice, but not control mice, caused intravascular neutrophil activation;
      perivascular neutrophil sequestration and tissue injuries were documented as
      elevations of vascular permeability and activated caspase-3. These changes were
      not observed if mice were injected with particles that had been subjected to
      hydrostatic recompression or particles that had been emulsified by incubation
      with polyethylene glycol telomere B surfactant. Hydrostatic pressure and
      surfactant incubation also altered the pattern of proteins expressed on the
      surface of particles. We conclude that proinflammatory events and vascular damage
      are due to enlargement of annexin V-coated particles and/or changes in surface
      marker protein pattern associated with provocative decompression. Injection of
      annexin V-coated particles from decompressed mice will recapitulate the
      pathophysiological vascular changes observed following decompression stress.

PMID- 21960661
TI  - Hepatic lipase gene -514C>T variant is associated with exercise training-induced
      changes in VLDL and HDL by lipoprotein lipase.
AB  - Our objective was to test the hypothesis that a common polymorphism in the
      hepatic lipase (HL) gene (LIPC -514C>T, rs1800588) influences aerobic exercise
      training-induced changes in TG, very-low-density lipoprotein (VLDL), and high
      density lipoprotein (HDL) through genotype-specific increases in lipoprotein
      lipase (LPL) activity and that sex may affect these responses. Seventy-six
      sedentary overweight to obese men and women aged 50-75 yr at risk for coronary
      heart disease (CHD) underwent a 24-wk prospective study of the LIPC -514 genotype
      specific effects of exercise training on lipoproteins measured enzymatically and
      by nuclear magnetic resonance, postheparin LPL and HL activities, body
      composition by dual energy x-ray absorptiometry and computer tomography scan, and
      aerobic capacity. CT genotype subjects had higher baseline total cholesterol, HDL
      C, HDL(2)-C, large HDL, HDL particle size, and large LDL than CC homozygotes.
      Exercise training elicited genotype-specific decreases in VLDL-TG (-22 vs. +7%; P
      < 0.05; CC vs. CT, respectively), total VLDL and medium VLDL, and increases in
      HDL-C (7 vs. 4%; P < 0.03) and HDL(3)-C with significant genotype*sex
      interactions for the changes in HDL-C and HDL(3)-C (P values = 0.01-0.02). There
      were also genotype-specific changes in LPL (+23 vs. -6%; P < 0.05) and HL (+7 vs.
      -24%; P < 0.01) activities, with LPL increasing only in CC subjects (P < 0.006)
      and HL decreasing only in CT subjects (P < 0.007). Reductions in TG, VLDL-TG,
      large VLDL, and medium VLDL and increases in HDL(3)-C and small HDL particles
      correlated significantly with changes in LPL, but not HL, activity only in CC
      subjects. This suggests that the LIPC -514C>T variant significantly affects
      training-induced anti-atherogenic changes in VLDL-TG, VLDL particles, and HDL
      through an association with increased LPL activity in CC subjects, which could
      guide therapeutic strategies to reduce CHD risk.

PMID- 21960662
TI  - Plane of vertebral movement eliciting muscle lengthening history in the low back
      influences the decrease in muscle spindle responsiveness of the cat.
AB  - Proprioceptive feedback is thought to play a significant role in controlling both
      lumbopelvic and intervertebral orientations. In the lumbar spine, a vertebra's
      positional history along the dorsal-ventral axis has been shown to alter the
      position, movement, and velocity sensitivity of muscle spindles in the multifidus
      and longissimus muscles. These effects appear due to muscle history. Because
      spinal motion segments have up to 6 degrees of freedom for movement, we were
      interested in whether the axis along which the history is applied differentially
      affects paraspinal muscle spindles. We tested the null hypothesis that the
      loading axis, which creates a vertebra's positional history, has no effect on a
      lumbar muscle spindle's subsequent response to vertebral position or movement.
      Identical displacements were applied along three orthogonal axes directly at the
      L(6) spinous process using a feedback motor system under displacement control.
      Single-unit nerve activity was recorded from 60 muscle spindle afferents in
      teased filaments from L(6) dorsal rootlets innervating intact longissimus or
      multifidus muscles of deeply anesthetized cats. Muscle lengthening histories
      along the caudal-cranial and dorsal-ventral axis, compared with the left-right
      axis, produced significantly greater reductions in spindle responses to vertebral
      position and movement. The spinal anatomy suggested that the effect of a
      lengthening history is greatest when that history had occurred along an axis
      lying within the anatomical plane of the facet joint. Speculation is made that
      the interaction between normal spinal mechanics and the inherent thixotropic
      property of muscle spindles poses a challenge for feedback and feedforward motor
      control of the lumbar spine.

PMID- 21960663
TI  - Seabuckthorn attenuates cardiac dysfunction and oxidative stress in isoproterenol
      induced cardiotoxicity in rats.
AB  - We investigated the effects of seabuckthorn (SBT) oil in isoproterenol (ISO)
      induced cardiotoxicity with reference to hemodynamic, antioxidant,
      histopathological, and ultrastructural parameters. Rats were administered SBT oil
      (5, 10, and 20 mL/kg per d) or vehicle orally for 30 days along with ISO (85
      mg/kg, subcutaneously, at 24-hour interval) on 29th and 30th day. On 31st day,
      ISO control rats showed cardiac dysfunction, increased lipid peroxidation,
      depletion of cardiac injury marker enzymes, and antioxidant activities.
      Myocardial necrosis, edema, and inflammation were evident from the light
      microscopic and ultrastructural changes. Seabuckthorn oil at the dose of 20 mL/kg
      per d significantly modulates hemodynamic and antioxidant derangements. The
      preventive role of SBT oil on ISO-induced cardiotoxicity was reconfirmed by
      histopathological and ultrastructural examinations. Thus, the present study
      reveals that SBT oil mitigates myocardial damage in ISO-induced cardiac injury in
      rats by maintaining hemodynamic, biochemical, histopathological, and
      ultrastructural perturbations owing to its free radical scavenging and
      antioxidant activities.

PMID- 21960664
TI  - 3-(2,6-dimethylphenyl)-2-selenoxo-1,3-thiazolidin-4-one suppresses hydrogen
      peroxide-induced cytotoxicity on PC12 cells via activation of MAPK.
AB  - We newly synthesized organic selenium compounds (5-membered ring compounds)
      including 2-selenoxo-1,3-thiazolidin-4-ones (compounds A) and 3-alkoxy-4,5
      dihydro-5-selenoxo-1H-1,2,4-triazole-1-carboxylates (compounds B). To address
      whether these compounds show antioxidative effects, we also examined their
      superoxide radical (O(2) (-))-scavenging effects. Moreover, we examined the
      effects of compound Aa on the activation of mitogen-activated protein
      kinase/extracellular signal-regulated protein kinases (MAPK/ERK1/2) and
      suppression of hydrogen peroxide-induced cytotoxicity in rat pheochromocytoma
      cells (PC12 cells). We evaluated the O(2) (-)-scavenging activities of the
      compounds by a chemiluminescence method, and activation of ERK1/2 in PC12 cells
      was evaluated by Western blot analysis. At 166 MUmol/L, the O(2) (-)-scavenging
      activities were markedly different among compounds A and B. 3-(2,6
      Dimethylphenyl)-2-selenoxo-1,3-thiazolidin-4-one (compound Aa) exhibited the
      strongest superoxide anion-scavenging activity among compounds A and B. The
      concentration necessary for 50% inhibition of the activity (IC(50)) of compound
      Aa was 25.9 MUmol/L. Compound Aa activated ERK1/2 of the PC12 cell, as did
      ebselen, and suppressed hydrogen peroxide-induced cytotoxicity more potently than
      ebselen. In addition, the toxicity of compound Aa was less than that of ebselen.
      From these results, it is assumed that compound Aa is a candidate drug to prevent
      oxidative stress-induced cell death.

PMID- 21960665
TI  - Learning and memory impairment induced by salvinorin A, the principal ingredient
      of Salvia divinorum, in wistar rats.
AB  - The effects of salvinorin A (Salvia divinorum principal ingredient), a potent
      kappa-opioid natural hallucinogen, on learning and memory were investigated.
      Wistar rats were tested in the 8-arm radial maze, for object recognition and
      passive avoidance tasks for spatial, episodic, and aversive memory. Attention was
      assessed using a latent inhibition task. Salvinorin A (80-640 MUg/kg subcutaneous
      [sc]) did not affect short-term memory, but it impaired spatial long-term memory.
      Episodic and aversive memories were impaired by salvinorin A (160-640 MUg/kg).
      Memory impairment was blocked by the selective kappa-opioid receptor antagonist,
      nor-binaltorphimine ([nor-B]; 0.5-1 mg/kg, intraperitoneal [ip]). Salvinorin A
      (160 MUg/kg) disrupted latent inhibition, after LiCl treatment, such as reduced
      sucrose intake, suggesting an attention would result in an impairment of
      cognitive behavior. These findings demonstrate for the first time that salvinorin
      A has deleterious effects on learning and memory, through a kappa-opioid receptor
      mechanism.

PMID- 21960666
TI  - Protective effects of aerosolized scopolamine against soman-induced acute
      respiratory toxicity in guinea pigs.
AB  - The protective efficacy of the antimuscarinic agent scopolamine was evaluated
      against soman (o-pinacolyl methylphosphonofluoridate [GD])-induced respiratory
      toxicity in guinea pigs. Anesthetized animals were exposed to GD (841 mg/m(3)) by
      microinstillation inhalation exposure and treated 30 seconds later with
      endotracheally aerosolized scopolamine (0.25 mg/kg) and allowed to recover for 24
      hours. Treatment with scopolamine significantly increased survival and reduced
      clinical signs of toxicity and body weight loss in GD-exposed animals. Analysis
      of bronchoalveolar lavage (BAL) fluid showed normalization of GD-induced
      increased cell death, total cell count, and protein following scopolamine
      treatment. The BAL fluid acetylcholinesterase and butyrylcholinesterase levels
      were also increased by scopolamine treatment. Respiratory dynamics parameters
      were normalized at 4 and 24 hours post-GD exposure in scopolamine-treated
      animals. Lung histology showed that scopolamine treatment reduced bronchial
      epithelial and subepithelial inflammation and multifocal alveolar septal edema.
      These results suggest that aerosolized scopolamine considerably protects against
      GD-induced respiratory toxicity.

PMID- 21960667
TI  - A preliminary 13-week oral toxicity study of ginger oil in male and female Wistar
      rats.
AB  - Zingiber officinale Roscoe, ginger, is a major spice extensively used in
      traditional medicine. The toxicity profile of ginger oil was studied by
      subchronic oral administration for 13 weeks at doses of 100, 250, and 500 mg/kg
      per day to 6 groups of Wistar rats (5/sex per dose). Separate groups of rats
      (5/sex per group) received either paraffin oil (vehicle) or were untreated and
      served as comparative control groups. There was no mortality and no decrease in
      body weight or food consumption as well as selective organ weights during the
      study period. Administration of ginger oil to rats did not produce any treatment
      related changes in hematological parameters, hepatic, renal functions, serum
      electrolytes, or in histopathology of selected organs. The major component of
      ginger oil was found to be zingiberene (31.08%), and initial studies indicated
      the presence of zingiberene in the serum after oral dosing. These results
      confirmed that ginger oil is not toxic to male and female rats following
      subchronic oral administrations of up to 500 mg/kg per day (no observed adverse
      effect level [NOAEL]).

PMID- 21960668
TI  - Pharmacokinetics, pharmacodynamics, and safety of ticagrelor in volunteers with
      severe renal impairment.
AB  - Ticagrelor, a P2Y(12) receptor antagonist, is approved in the European Union and
      the US for the prevention of thrombotic events in patients with acute coronary
      syndromes. Renal dysfunction potentially affects drug disposition. Ticagrelor
      pharmacokinetics, pharmacodynamics, and safety in renal impairment were assessed.
      A single 180-mg ticagrelor dose was administered to volunteers with severe renal
      impairment (creatinine clearance [CrCL] < 30 mL/min) and normal renal function
      (CrCL >= 80 mL/min; n = 10/group). Severe renal impairment did not significantly
      affect ticagrelor's pharmacokinetics, pharmacodynamics, or safety. Ticagrelor
      absorption and AR-C124910XX (active metabolite) formation were rapid. In renally
      impaired volunteers, ticagrelor mean maximum concentration (C(max)) and area
      under the plasma concentration-time curve from zero to infinity were 20% lower
      and for AR-C124910XX was 17% higher versus normal volunteers. Ticagrelor systemic
      exposure was low in 3 volunteers (CrCL < 20 mL/min), but data were variable.
      Onset and offset of final-extent inhibition of platelet aggregation were
      comparable in both groups. Inhibition of platelet aggregation parameters and
      profiles were similar between groups, indicating that platelet sensitivity to
      ticagrelor was not affected by severe renal impairment. Ticagrelor was well
      tolerated in both groups with few adverse events. No ticagrelor dose adjustment
      is required for renally impaired patients.

PMID- 21960669
TI  - Absence of pharmacokinetic interaction between intravenous peramivir and oral
      oseltamivir or rimantadine in humans.
AB  - Peramivir, an intravenously administered neuraminidase inhibitor, may be used
      concomitantly with other influenza antivirals. Two studies were conducted to
      assess the potential for pharmacokinetic interactions of peramivir when
      coadministered with oseltamivir or rimantadine. Twenty-one healthy subjects were
      enrolled in each randomized, open-label, crossover study, and they received 1
      intravenous dose of peramivir (600 mg), 1 oral dose of oseltamivir (75 mg) or
      rimantadine (100 mg), or a combination of peramivir with oseltamivir or
      rimantadine. Assessment of the 90% confidence interval for the geometric mean
      ratio of peramivir and oseltamivir carboxylate or rimantadine pharmacokinetic
      parameters showed no effect of oseltamivir or rimantadine on the pharmacokinetics
      of peramivir and no effect of peramivir on the pharmacokinetics of oseltamivir
      carboxylate or rimantadine. The drugs were well tolerated. These results suggest
      no reason to expect an effect of concomitant administration of oseltamivir or
      rimantadine on the safety profile of peramivir in patients with influenza.

PMID- 21960670
TI  - Linezolid pharmacokinetics in patients with acute renal failure undergoing
      continuous venovenous hemodiafiltration.

PMID- 21960672
TI  - Phosphatase and tensin homolog (PTEN) gene mutations and autism: literature
      review and a case report of a patient with Cowden syndrome, autistic disorder,
      and epilepsy.
AB  - Phosphatase and tensin homolog (PTEN) gene mutations are associated with a
      spectrum of clinical disorders characterized by skin lesions, macrocephaly,
      hamartomatous overgrowth of tissues, and an increased risk of cancers. Autism has
      rarely been described in association with these variable clinical features. At
      present, 24 patients with phosphatase and tensin homolog gene mutation, autism,
      macrocephaly, and some clinical findings described in phosphatase and tensin
      homolog syndromes have been reported in the literature. We describe a 14-year-old
      boy with autistic disorder, focal epilepsy, severe and progressive macrocephaly,
      and multiple papular skin lesions and palmoplantar punctate keratoses,
      characteristic of Cowden syndrome. The boy has a de novo phosphatase and tensin
      homolog gene mutation. Our patient is the first case described to present a
      typical Cowden syndrome and autism associated with epilepsy.

PMID- 21960671
TI  - Phenobarbital and temperature profile during hypothermia for hypoxic-ischemic
      encephalopathy.
AB  - Data from the whole-body hypothermia trial was analyzed to examine the effects of
      phenobarbital administration prior to cooling (+PB) on the esophageal temperature
      (T (e)) profile, during the induction phase of hypothermia. A total of 98 infants
      were analyzed. At enrollment, +PB infants had a higher rate of severe hypoxic
      ischemic encephalopathy and clinical seizures and lower T (e) and cord pH than
      infants that have not received phenobarbital (-PB). There was a significant
      effect of phenobarbital itself and an interaction between phenobarbital and time
      in the T (e) profile. Mean T (e) in the +PB group was lower than in the -PB
      group, and the differences decreased over time. In +PB infants, the time to
      surpass target T (e) of 33.5 degrees C and to reach the minimum T (e) during
      overshoot were shorter. In conclusion, the administration of phenobarbital before
      cooling was associated with changes that may reflect a reduced thermogenic
      response associated with barbiturates.

PMID- 21960673
TI  - Risk factors and clinical outcomes of childhood ischemic stroke in a single
      Korean tertiary care center.
AB  - A 10-year, retrospective review of the risk factors and clinical outcome of
      childhood ischemic stroke treated in a single tertiary care center was conducted.
      Sixty-two children were identified (33 boys and 29 girls), ages 1 month to 17
      years. Risk factors included vasculopathy (35.5%), cardiac disease (17.4%),
      metabolic disorder (14.5%), infection (14.5%), and coagulopathy (1.6%). Nine
      patients (14.5%) had no identifiable cause of stroke and 1 patient had 2 risk
      factors. Hemiplegia (69.3%) and seizures (32.3%) were the most common presenting
      features, and seizures were significantly more frequent in children <12 months of
      age than in older children (71.4% vs 20.8%, P = .001). Recurrence of stroke
      occurred in 55.6% of patients with metabolic disorder, 33.3% of those with
      cardiac disease, and 19.0% of those with vasculopathy. Vasculopathy including
      moyamoya disease was the most important risk factor for ischemic stroke in Korea,
      and their prognosis were varied with the etiology of stroke.

PMID- 21960674
TI  - Distinct features of congenital disorder of glycosylation type IIx in Kuwait: a
      case report.
AB  - Congenital disorders of glycosylation are a rare but complex group of inborn
      metabolic diseases that result in carbohydrate-deficient glycoproteins.
      Biochemical and clinical features of both types I and II of this group of
      disorders have been well characterized and reported from various parts of the
      world except the Middle East. The authors describe a patient with congenital
      disorders of glycosylation type IIx who presented with psychomotor retardation,
      development delay, hypotonia, and hepatomegaly. Computed tomography scan of the
      liver showed multiple hepatic focal lesions, and magnetic resonance imaging
      revealed mild brain and corpus callosum atrophy. This is the first report of
      congenital disorders of glycosylation type IIx from Kuwait that shows its
      prevalence and distinct features in the Middle East.

PMID- 21960675
TI  - Toward chemotherapy-free treatment of CLL.

PMID- 21960676
TI  - TCR expression; quantitative easing by CD3.

PMID- 21960677
TI  - Targeting Bcl-2 in CLL: cui bono?

PMID- 21960678
TI  - "Baby" red cells to the rescue.

PMID- 21960679
TI  - High stakes immunology.

PMID- 21960680
TI  - Extracellular histones zap platelets.

PMID- 21960681
TI  - In memoriam: James Wyatt Bawden.

PMID- 21960683
TI  - Thermal treatments modulate bacterial adhesion to dental enamel.
AB  - Numerous studies have demonstrated the effects of laser-induced heat on
      demineralization of enamel; however, no studies have investigated the link
      between heat/laser-induced changes in physicochemical properties and bacterial
      adhesion. In this study, we investigated the effects of thermal treatment on
      surface properties of enamel such as hydrophobicity and zeta potential. Bacterial
      adhesion to treated surfaces was characterized by confocal laser scanning
      microscopy, and adhesion force was quantified by atomic force microscopy. The
      hydrophobicity of enamel increased after heating (p < 0.05), and the zeta
      potential of heated enamel became more negative than that of the control (p <
      0.01). Streptococcus oralis and S. mitis were more hydrophilic than S. sanguis,
      with more negative zeta potential (all p < 0.01). S. mitis and S. oralis occupied
      significantly less area on enamel after being heated (p < 0.05). Heating reduced
      the adhesion force of both S. mitis and S. oralis to enamel with or without
      saliva coating. Reduction of adhesion force was statistically significant for S.
      mitis (p < 0.01), whereas that of S. oralis was not statistically significant (p
      > 0.05). Heating did not affect the adhesion of S. sanguis with or without saliva
      coating. In conclusion, thermal treatment and photothermal/laser treatments may
      modulate the physicochemical properties of enamel, preventing the adhesion of
      some bacterial species.

PMID- 21960682
TI  - Ternary phase diagram of model dentin adhesive exposed to over-wet environments.
AB  - When adhesives and/or composites are bonded to the tooth, water in the
      environment can interfere with proper interface formation. Formation of water
      blisters and phase separation at the adhesive/dentin interface have appeared as
      new types of bond defects. To better understand this problem, we determined the
      near-equilibrium partition of the hydrophobic/hydrophilic components when exposed
      to over-wet environments. Model methacrylate-based adhesives were mixed with
      different amounts of water to yield well-separated aqueous and resin phases. It
      was found that less than 0.1% BisGMA but nearly one-third of the HEMA diffused
      into the aqueous phase, leaving the remaining resin phase relatively hydrophobic.
      A partial phase diagram was created for the ternary BisGMA/HEMA/water system. All
      the experimental phase partitioning data were plotted, and the points lay on a
      binodal curve that separated the single-phase region from the two-phase region.
      We obtained the 3 tie lines by connecting the 2 points of each conjugate pair of
      the phase partitioning data from the 3 sets of tripartite mixtures. Information
      about solubility, water miscibility, distribution ratio, and phase partitioning
      behavior could be obtained quantitatively. This type of phase diagram will
      provide a more thorough understanding of current adhesive performance and
      elucidate directions for further improvement.

PMID- 21960684
TI  - Caveolin-1 opens endothelial cell junctions by targeting catenins.
AB  - AIMS: A fundamental phenomenon in inflammation is the loss of endothelial barrier
      function, in which the opening of endothelial cell junctions plays a central
      role. However, the molecular mechanisms that ultimately open the cell junctions
      are largely unknown. METHODS AND RESULTS: Impedance spectroscopy, biochemistry,
      and morphology were used to investigate the role of caveolin-1 in the regulation
      of thrombin-induced opening of cell junctions in cultured human and mouse
      endothelial cells. Here, we demonstrate that the vascular endothelial (VE)
      cadherin/catenin complex targets caveolin-1 to endothelial cell junctions.
      Association of caveolin-1 with VE-cadherin/catenin complexes is essential for the
      barrier function decrease in response to the pro-inflammatory mediator thrombin,
      which causes a reorganization of the complex in a rope ladder-like pattern
      accompanied by a loss of junction-associated actin filaments. Mechanistically, we
      show that in response to thrombin stimulation the protease-activated receptor 1
      (PAR-1) causes phosphorylation of caveolin-1, which increasingly associates with
      beta- and gamma-catenin. Consequently, the association of beta- and gamma-catenin
      with VE-cadherin is weakened, thus allowing junction reorganization and a
      decrease in barrier function. Thrombin-induced opening of cell junctions is lost
      in caveolin-1-knockout endothelial cells and after expression of a Y/F-caveolin-1
      mutant but is completely reconstituted after expression of wild-type caveolin-1.
      CONCLUSION: Our results highlight the pivotal role of caveolin-1 in VE-cadherin
      mediated cell adhesion via catenins and, in turn, in barrier function regulation.

PMID- 21960685
TI  - The natural cardioprotective particle HDL modulates connexin43 gap junction
      channels.
AB  - AIMS: High-density lipoprotein (HDL) is known for its cardioprotective properties
      independent from its cholesterol transport activity. These properties are
      mediated by activation of kinases such as protein kinase C (PKC). Connexin43
      (Cx43) is a gap junction protein present in ventricular cardiomyocytes. PKC
      dependent phosphorylation modifies Cx43 gap junction channel properties and is
      involved in cardioprotection. We hypothesized that cardioprotective properties of
      HDL may be mediated in part by affecting Cx43 gap junction channels. METHODS AND
      RESULTS: Neonatal rat cardiomyocytes were treated with HDL and Cx43
      phosphorylation was evaluated by western blotting and immunofluorescence. We
      found that HDL promoted phosphorylation of Cx43 with a maximal induction at 5
      min, which was inhibited by pre-treatment with various PKC inhibitors.
      Sphingosine-1-phosphate (S1P), a component of HDL, induced effects that were
      similar to those of HDL. These compounds significantly reduced diffusion of
      fluorescent dye among cardiomyocytes (~50%) which could be prevented by PKC
      inhibition. As observed during optical recordings of transmembrane voltage, HDL
      and S1P depressed impulse conduction only minimally (<5%). Moreover, 5 min of HDL
      and S1P treatment at the onset of reperfusion significantly reduced infarct size
      (~50%) in response to 30 min ischaemia in ex vivo experiments. CONCLUSION: Short
      term treatment with HDL or S1P induces phosphorylation of Cx43 by a PKC-dependent
      pathway. HDL-induced phosphorylation of Cx43 reduced the diffusion of large
      tracer molecules between cells, whereas impulse conduction was maintained.
      Moreover, 5 min treatment with HDL confers cardioprotection against
      ischaemia/reperfusion injury. These results link Cx43 for the first time to the
      short-term cardioprotective effects of HDL.

PMID- 21960687
TI  - Decreased brain sigma-1 receptor contributes to the relationship between heart
      failure and depression.
AB  - AIMS: Depression often coexists with cardiovascular disease, such as hypertension
      and heart failure, in which sympathetic hyperactivation is critically involved.
      Reduction in the brain sigma-1 receptor (S1R) functions in depression
      pathogenesis via neuronal activity modulation. We hypothesized that reduced brain
      S1R exacerbates heart failure, especially with pressure overload via sympathetic
      hyperactivation and worsening depression. METHODS AND RESULTS: Male Institute of
      Cancer Research mice were treated with aortic banding and, 4 weeks thereafter,
      fed a high-salt diet for an additional 4 weeks to accelerate cardiac dysfunction
      (AB-H). Compared with sham-operated controls (Sham), AB-H showed augmented
      sympathetic activity, decreased per cent fractional shortening, increased left
      ventricular dimensions, and significantly lower brain S1R expression.
      Intracerebroventricular (ICV) infusion of S1R agonist PRE084 increased brain S1R
      expression, lowered sympathetic activity, and improved cardiac function in AB-H.
      ICV infusion of S1R antagonist BD1063 increased sympathetic activity and
      decreased cardiac function in Sham. Tail suspension test was used to evaluate the
      index of depression-like behaviour, with immobility time and strain amplitude
      recorded as markers of struggle activity using a force transducer. Immobility
      time increased and strain amplitude decreased in AB-H compared with Sham, and
      these changes were attenuated by ICV infusion of PRE084. CONCLUSION: These
      results indicate that decreased brain S1R contributes to the relationship between
      heart failure and depression in a mouse model of pressure overload.

PMID- 21960686
TI  - High intake of saturated fat, but not polyunsaturated fat, improves survival in
      heart failure despite persistent mitochondrial defects.
AB  - AIMS: The impact of a high-fat diet on the failing heart is unclear, and the
      differences between polyunsaturated fatty acids (PUFA) and saturated fat have not
      been assessed. Here, we compared a standard low-fat diet to high-fat diets
      enriched with either saturated fat (palmitate and stearate) or PUFA (linoleic and
      alpha-linolenic acids) in hamsters with genetic cardiomyopathy. METHODS AND
      RESULTS: Male delta-sarcoglycan null Bio TO2 hamsters were fed a standard low-fat
      diet (12% energy from fat), or high-fat diets (45% fat) comprised of either
      saturated fat or PUFA. The median survival was increased by the high saturated
      fat diet (P< 0.01; 278 days with standard diet and 361 days with high saturated
      fat)), but not with high PUFA (260 days) (n = 30-35/group). Body mass was
      modestly elevated (~10%) in both high fat groups. Subgroups evaluated after 24
      weeks had similar left ventricular chamber size, function, and mass.
      Mitochondrial oxidative enzyme activity and the yield of interfibrillar
      mitochondria (IFM) were decreased to a similar extent in all TO2 groups compared
      with normal F1B hamsters. Ca(2+)-induced mitochondrial permeability transition
      pore opening was enhanced in IFM in all TO2 groups compared with F1B hamsters,
      but to a significantly greater extent in those fed the high PUFA diet compared
      with the standard or high saturated fat diet. CONCLUSION: These results show that
      a high intake of saturated fat improves survival in heart failure compared with a
      high PUFA diet or low-fat diet, despite persistent mitochondrial defects.

PMID- 21960688
TI  - Apropos "Dengue virus immunoglobulin M detection in a reference laboratory
      setting during the 2010 dengue virus outbreak on Caribbean islands".

PMID- 21960689
TI  - Impact of EGFR genetic variants on glioma risk and patient outcome.
AB  - BACKGROUND: The epidermal growth factor receptor (EGFR) regulates important
      cellular processes and is frequently implicated in human tumors. Three EGFR
      polymorphisms have been described as having a transcriptional regulatory
      function: two single-nucleotide polymorphisms in the essential promoter region, 
      216G/T and -191C/A, and a polymorphic (CA)(n) microsatellite sequence in intron
      1. We aimed to elucidate the roles of these EGFR polymorphisms in glioma
      susceptibility and prognosis. METHODS: We conducted a case-control study with 196
      patients with glioma and 168 cancer-free controls. Unconditional multivariate
      logistic regression models were used to calculate ORs and 95% confidence
      intervals. A Cox regression model was used to evaluate associations with patient
      survival. False-positive report probabilities were also assessed. RESULTS: None
      of the EGFR -216G/T variants was significantly associated with glioma risk. The 
      191C/A genotype was associated with higher risk for glioma when the (CA)(n)
      alleles were classified as short for <=16 or <=17 repeats. Independently of the
      (CA)(n) repeat cutoff point used, shorter (CA)(n) repeat variants were
      significantly associated with increased risk for glioma, particularly
      glioblastoma and oligodendroglioma. In all tested models with different (CA)(n)
      cutoff points, only -191C/A genotype was consistently associated with improved
      survival of patients with glioblastoma. CONCLUSIONS: Our findings implicate EGFR 
      191C/A and the (CA)(n) repeat polymorphisms as risk factors for gliomas, and
      suggest -191C/A as a prognostic marker in glioblastoma. IMPACT: Our data support
      a role of these EGFR polymorphisms in determining glioma susceptibility, with
      potential relevance for molecularly based stratification of patients with
      glioblastoma for individualized therapies.

PMID- 21960690
TI  - Family history of breast cancer in relation to tumor characteristics and
      mortality in a population-based study of young women with invasive breast cancer.
AB  - BACKGROUND: Inherited predisposition may be associated with distinctive breast
      cancer phenotypes and/or mortality. Past studies have had inconsistent results
      and little is known about the contributions of screening and treatment. METHODS:
      Within a population-based cohort of 1,260 women diagnosed with invasive breast
      cancer before age 46, we assessed how family history of breast cancer relates to
      mortality and tumor characteristics. Analyses were repeated excluding BRCA1/BRCA2
      carriers. Medical records were reviewed for treatment history and tumors were
      centrally reviewed and tested. Cox proportional hazard modeling was used to
      assess the risk of dying in relation to family history; logistic regression was
      used to assess the association of family history to tumor characteristics.
      RESULTS: Compared with women with no family history, women with first-degree
      family history of breast cancer had a 40% reduction (95% CI: 0.5-0.8) in the risk
      of dying. Mortality in women with only a second-degree family history was similar
      to those with no family history. The risk of dying was further reduced in those
      with a greater number of affected relatives. These relationships did not seem to
      be attributable to differences in screening, detection method, or treatment.
      Tumors in women with a first-degree family history had generally more favorable
      prognostic profiles. CONCLUSION: Our findings suggest that breast cancer patients
      with a first-degree family history, compared with their counterparts without such
      a profile, may have a better prognosis. IMPACT: These findings support the need
      for future research directed at replicating these results and identifying factors
      underlying this possible relationship.

PMID- 21960691
TI  - Deriving valid population-based cancer survival estimates in the presence of
      nonnegligible proportions of cancers notified by death certificates only.
AB  - BACKGROUND: Studies of cancer survival by population-based cancer registries are
      a key component in monitoring progress against cancer. Patients notified by death
      certificates only (DCO) are commonly excluded from such studies. The validity of
      this "exclude DCO" approach has been questioned and an alternative "correct for
      DCO" approach has been proposed. METHODS: We assess the validity of both the
      "exclude DCO" approach and the "correct for DCO" approach using model
      calculations. We illustrate implications for population-based cancer survival
      analyses by analyses of 5-year relative survival of cancer patients in Saarland,
      Germany. RESULTS: The "exclude DCO" approach provides (too) optimistic survival
      estimates and the "correct for DCO" approach provides (too) pessimistic survival
      estimates under plausible assumptions. For example, in case of true survival of
      50%, underascertainment of 5% of surviving patients and of 15% of dying patients
      (yielding a proportion of DCO cases of 7.7%), the two approaches would provide
      survival rate estimates of 52.8% and 48.8%, respectively. The difference of
      survival estimates obtained with both approaches increases with incompleteness of
      registration and the proportion of DCO cases. Trace back of DCO cases shifts
      survival estimates from the former toward the latter estimate. CONCLUSIONS: In
      case of nonnegligible DCO proportions, cancer survival studies should not be
      exclusively based on either the "exclude DCO" or the "correct for DCO" approach.
      A combination of estimates from both approaches may be useful to delineate a
      plausibility range for true survival. IMPACT: Our results may help to enhance
      validity and comparability of population-based cancer survival estimates.

PMID- 21960693
TI  - A genome-wide survey over the ChIP-on-chip identified androgen receptor-binding
      genomic regions identifies a novel prostate cancer susceptibility locus at
      12q13.13.
AB  - BACKGROUND: The molecular mechanisms for the genome-wide association studies
      (GWAS)-identified prostate cancer (PCa) risk-associated single-nucleotide
      polymorphisms (SNP) remain largely unexplained. One recent finding that the PCa
      risk SNPs are enriched in genomic regions containing androgen receptor (AR)
      binding sites has suggested altered AR signaling as a potentially important
      mechanism. METHODS: To explore novel associations by leveraging this knowledge,
      we utilized a meta-analysis previously done over SNPs harbored in ChIP-on-chip
      identified AR-binding genomic regions using the GWAS data from the Johns Hopkins
      Hospital (JHH) and the Cancer Genetic Markers of Susceptibility (CGEMS) study,
      and subsequently evaluated the top associations in a third population from the
      CAncer of the Prostate in Sweden (CAPS) study. RESULTS: One SNP (rs4919743: G>A),
      located at the KRT8 locus at 12q13.13 which encodes a keratin protein (K8) long
      used as a prostate epithelial malignancy marker and implicated in the
      tumorigenesis of several cancer types, was identified to be associated with PCa
      risk. The frequency of its minor "A" allele was consistently higher in PCa cases
      than in controls in all three study populations, with a combined OR of 1.22 (95%
      CI: 1.13-1.32) and an overall P value of 4.50 * 10(-7) (Bonferroni corrected, P =
      0.006). CONCLUSION: We have identified a novel genetic locus that is associated
      with PCa risk. IMPACT: This study illustrated the great potential of prior
      biological knowledge in facilitating the search for novel disease-associated
      genetic loci. This finding warrants further replication in other studies.

PMID- 21960692
TI  - Tumor and salivary matrix metalloproteinase levels are strong diagnostic markers
      of oral squamous cell carcinoma.
AB  - BACKGROUND: The matrix metalloproteinases (MMP) cause degradation of the
      extracellular matrix and basement membranes, and thus may play a key role in
      cancer development. METHODS: In our search for biomarkers for oral squamous cell
      carcinomas (OSCC), we compared primary OSCC, oral dysplasia and control subjects
      with respect to: (i) expression of MMP1, MMP3, MMP10, and MMP12 in oral
      epithelial tissue using Affymetrix U133 2.0 Plus GeneChip arrays, followed by
      quantitative reverse transcription-PCR (qRT-PCR) for MMP1, and (ii) determination
      of MMP1 and MMP3 concentrations in saliva. RESULTS: MMP1 expression in primary
      OSCC (n = 119) was >200-fold higher (P = 7.16 * 10(-40)) compared with expression
      levels in nonneoplastic oral epithelium from controls (n = 35). qRT-PCR results
      on 30 cases and 22 controls confirmed this substantial differential expression.
      The exceptional discriminatory power to separate OSCC from controls was validated
      in two independent testing sets (AUC% = 100; 95% CI: 100-100 and AUC% = 98.4; 95%
      CI: 95.6-100). Salivary concentrations of MMP1 and MMP3 in OSCC patients (33
      stage I/II, 26 stage III/IV) were 6.2 times (95% CI: 3.32-11.73) and 14.8 times
      (95% CI: 6.75-32.56) higher, respectively, than in controls, and displayed an
      increasing trend with higher stage disease. CONCLUSION: Tumor and salivary MMPs
      are robust diagnostic biomarkers of OSCC. IMPACT: The capacity of MMP gene
      expression to identify OSCC provides support for further investigation into MMPs
      as potential markers for OSCC development. Detection of MMP proteins in saliva in
      particular may provide a promising means to detect and monitor OSCC
      noninvasively.

PMID- 21960694
TI  - Common polymorphisms in the adiponectin and its receptor genes, adiponectin
      levels and the risk of prostate cancer.
AB  - BACKGROUND: Adiponectin, an insulin-sensitizing adipokine, is inversely
      associated with adiposity and prostate cancer risk and progression. However, the
      role of genetic variation in the adiponectin (ADIPOQ) and receptor genes
      (ADIPOR1/R2) in prostate cancer is largely unknown. METHODS: In a nested case
      control study of 1,286 cases and 1,267 controls within the Physicians' Health
      Study, we evaluated 29 common single-nucleotide polymorphisms (SNP) in ADIPOQ (n
      = 13), ADIPOR1 (n = 5), and ADIPOR2 (n = 11) in relation to the risk of prostate
      cancer. In subgroups, we also evaluated the association of genotype and
      circulating adiponectin levels (n = 951) and prostate tumor expression of insulin
      receptor (IR) and insulin-like growth factor 1 (IGF-IR) receptor (n = 181).
      RESULTS: Among the 12 tagging polymorphisms in ADIPOQ, four (rs266729, rs182052,
      rs822391, and rs2082940) were significantly associated (P < 0.05) with overall
      prostate cancer risk, with no significant difference by tumor grade or clinical
      stage. Two of the risk SNPs (rs266729 and rs182052) plus four other SNPs
      (rs16861209, rs17366568, rs3774261, and rs7639352) were also associated with
      plasma adiponectin levels, and three of these (rs1686109, rs17366568, and
      rs3774261) were also significantly associated with IR expression in prostate
      tumor tissue. One additional SNP was associated with IGFI-R tumor tissue
      expression (rs16861205). None of the 16 variants in ADIPOR1/R2 were related to
      cancer risk or circulating adiponectin levels. CONCLUSIONS: Common variants in
      the adiponectin gene were associated with prostate cancer risk, plasma
      adiponectin levels, and IR or IGF-IR expression in the prostate tumor. IMPACT:
      These genotype-phenotype associations support the biological relevance of
      adiponectin for prostate carcinogenesis, particularly in earlier stages of
      development.

PMID- 21960695
TI  - Fetal exposure to maternal and paternal smoking and the risks of wheezing in
      preschool children: the Generation R Study.
AB  - BACKGROUND: Previous studies have suggested that fetal smoke exposure is
      associated with increased risks of wheezing during childhood. The underlying
      pathways are unknown. We examined the associations of parental smoking during
      pregnancy with wheezing in preschool children and whether these associations are
      explained by postnatal smoke exposure or small for gestational age at birth.
      METHODS: This study was embedded in a population-based prospective cohort study.
      Parental smoking was prospectively assessed by questionnaires. Wheezing was
      reported at 1 to 4 years. Small for gestational age at birth was available from
      registries. The analyses were based on 4,574 subjects. RESULTS: Maternal smoking
      during the first trimester only was not associated with wheezing. Continued
      maternal smoking in pregnancy was associated with the risk of wheezing at 1 to 4
      years (P for trends < .05). The strongest effect estimates were observed for
      frequent wheezing (four or more episodes of wheezing per year) until age 3 years
      (OR [95% CI]: age 1,1.64 [1.12-2.40]; age 2, 1.64 [1.01-2.64]; age 3, 2.19 [1.24
      3.86]). Among children of nonsmoking mothers, fetal exposure to paternal smoking
      was not consistently associated with the risks of wheezing. The associations of
      continued maternal smoking during pregnancy with wheezing symptoms were
      independent of postnatal smoke exposure or small for gestational age at birth.
      CONCLUSIONS: Fetal exposure to continued maternal smoking is associated with
      increased risks of wheezing in preschool children. Further research is needed to
      explore the effects of paternal smoking. Diminishing maternal smoking before
      conception or in early pregnancy is likely to have the greatest impact on
      reducing childhood wheezing.

PMID- 21960696
TI  - Six-minute walk distance predictors, including CT scan measures, in the COPDGene
      cohort.
AB  - BACKGROUND: Exercise tolerance in COPD is only moderately well predicted by
      airflow obstruction assessed by FEV(1). We determined whether other phenotypic
      characteristics, including CT scan measures, are independent predictors of 6-min
      walk distance (6MWD) in the COPDGene cohort. METHODS: COPDGene recruits non
      Hispanic Caucasian and African American current and ex-smokers. Phenotyping
      measures include postbronchodilator FEV(1) % predicted and inspiratory and
      expiratory CT lung scans. We defined % emphysema as the percentage of lung voxels
      < -950 Hounsfield units on the inspiratory scan and % gas trapping as the
      percentage of lung voxels < -856 Hounsfield units on the expiratory scan.
      RESULTS: Data of the first 2,500 participants of the COPDGene cohort were
      analyzed. Participant age was 61 +/- 9 years; 51% were men; 76% were non-Hispanic
      Caucasians, and 24% were African Americans. Fifty-six percent had spirometrically
      defined COPD, with 9.3%, 23.4%, 15.0%, and 8.3% in GOLD (Global Initiative for
      Chronic Obstructive Lung Disease) stages I to IV, respectively. Higher %
      emphysema and % gas trapping predicted lower 6MWD (P < .001). However, in a given
      spirometric group, after adjustment for age, sex, race, and BMI, neither %
      emphysema nor % gas trapping, or their interactions with FEV(1) % predicted,
      remained a significant 6MWD predictor. In a given spirometric group, only 16% to
      27% of the variance in 6MWD could be explained by age, male sex, Caucasian race,
      and lower BMI as significant predictors of higher 6MWD. CONCLUSIONS: In this
      large cohort of smokers in a given spirometric stage, phenotypic characteristics
      were only modestly predictive of 6MWD. CT scan measures of emphysema and gas
      trapping were not predictive of 6MWD after adjustment for other phenotypic
      characteristics.

PMID- 21960697
TI  - Progressive changes in right ventricular geometric shortening and long-term
      survival in pulmonary arterial hypertension.
AB  - BACKGROUND: Until now, many investigators have focused on describing right
      ventricular (RV) dysfunction in groups of patients with pulmonary arterial
      hypertension (PAH), but very few have addressed the deterioration of RV function
      over time. The aim of this study was to investigate time courses of RV geometric
      changes during the progression of RV failure. METHODS: Forty-two patients with
      PAH were selected who underwent right-sided heart catheterization and cardiac MRI
      at baseline and after 1-year follow-up. Based on the survival after this 1-year
      run-in period, patients were classified into two groups: survivors (26 patients;
      subsequent survival of > 4 years) and nonsurvivors (16 patients; subsequent
      survival of < 4 years). Four-chamber cine imaging was used to quantify RV
      longitudinal shortening (apex-base distance change), RV transverse shortening
      (septum-free wall distance change), and RV fractional area change (RVFAC) between
      end diastole and end systole. RESULTS: Longitudinal shortening, transverse
      shortening, and RVFAC measured at the beginning of the run-in period and 1 year
      later were significantly higher in subsequent survivors than in nonsurvivors (P <
      .05). Longitudinal shortening did not change during the run-in period in either
      patient group. Transverse shortening and RVFAC did not change during the run-in
      period in subsequent survivors but did decrease in subsequent nonsurvivors (P <
      .05). This decrease was caused by increased leftward septal bowing. CONCLUSIONS:
      Progressive RV failure in PAH is associated with a parallel decline in
      longitudinal and transverse shortening until a floor effect is reached for
      longitudinal shortening. A further reduction of RV function is due to progressive
      leftward septal displacement. Because transverse shortening incorporates both
      free wall and septum movements, this parameter can be used to monitor the decline
      in RV function in end-stage PAH.

PMID- 21960698
TI  - Changes of health-related quality of life in critically ill octogenarians: a
      follow-up study.
AB  - BACKGROUND: Intensivists frequently are concerned about whether octogenarians
      actually will benefit from ICU admission. We studied changes in health-related
      quality of life (HRQOL) 6 months following ICU discharge in those patients.
      METHODS: We performed a long-term prospective study in a medical-surgical ICU.
      Patients aged >= 80 years (n = 129) and < 80 years (n = 620) admitted for > 48 h
      were included. We used the Medical Outcomes Study 36-item short form (SF-36) to
      evaluate HRQOL before ICU admission (using proxies), at ICU discharge, at
      hospital discharge, and at 3 and 6 months following ICU discharge, using a linear
      mixed model. RESULTS: At 6 months after ICU discharge, 49 patients aged >= 80
      years and 352 patients aged < 80 years could be evaluated. At ICU discharge,
      physical functioning was far lower than mental functioning (physical component
      score, 24.9; mental component score, 46.1) in the octogenerians. Most SF-36
      dimensions showed significant improvement over time (all P < .01, except role
      emotional [P = .038] and bodily pain [P = .77]). In the octogenarians, mean SF-36
      scores 6 months after ICU discharge were comparable to baseline in all
      dimensions. Most dimensions of the SF-36 were not significantly lower in
      surviving octogenarians at 6 months after ICU discharge compared with the normal
      population. CONCLUSIONS: We demonstrated a good recovery of HRQOL in
      octogenarians surviving critical illness. The findings suggest that denying
      admission to the ICU should not just rely on old age.

PMID- 21960699
TI  - Effects of nebulized bronchodilator therapy on heart rate and arrhythmias in
      critically ill adult patients.
AB  - BACKGROUND: Tachycardia and tachyarrhythmias are associated with increased
      morbidity and mortality in adult patients in the ICU. This study examines the
      effects of nebulized bronchodilator therapy (albuterol and ipratropium) on heart
      rate and arrhythmias in this population and tests the proposition that
      levalbuterol is safer than albuterol in that regard. METHODS: The design was a
      randomized, single-blind, crossover, prospective study in 70 critically ill adult
      patients treated with nebulized bronchodilators. Patients were randomized to
      nebulized albuterol alternating with levalbuterol every 4 to 6 h. Group A
      received albuterol 2.5 mg alternating with levalbuterol 0.63 mg. Group B received
      albuterol 2.5 mg alternating with levalbuterol 1.25 mg. All patients received
      nebulized ipratropium bromide with each treatment. Heart rate was recorded before
      and after each treatment. Cardiac rhythm was continuously monitored using
      electronic telemetry units. RESULTS: In group A, mean +/- SD change in heart rate
      after albuterol 2.5 mg (n = 303) was 0.89 +/- 4.5 beats/min compared with 0.85 +/
      5.3 beats/min after levalbuterol 0.63 mg (n = 301) (P = .89). In group B (n =
      114), heart rate decreased 0.16 +/- 5.1 beats/min after albuterol 2.5 mg compared
      with an increase of 1.4 +/- 5.4 beats/min after levalbuterol 1.25 mg (n = 118) (P
      = .03). Five events of arrhythmias (0.6%) occurred during the course of 836
      treatments. Four consisted of occasional premature ventricular contractions. Only
      one patient stopped treatment because of a 5-beat run of ventricular tachycardia
      (one in 70 patients [1.4%]). CONCLUSIONS: In critically ill adult patients,
      nebulized albuterol and ipratropium does not cause significant tachycardia or
      tachyarrhythmias. Substitution of levalbuterol for albuterol to avoid tachycardia
      and tachyarrhythmias is unwarranted. TRIAL REGISTRY: ClinicalTrials.gov; No.:
      NCT01151579; URL: www.clinicaltrials.gov.

PMID- 21960700
TI  - Steady antibiotic release from biodegradable beads in the pleural cavity: an in
      vitro and in vivo study.
AB  - BACKGROUND: Inadequate localized drug concentrations and systemic adverse effects
      are among the concerns when regional infections are treated with systemic
      antibiotics. We designed and fabricated a poly(D,L)-lactide-co-glycolide (PLGA)
      based biodegradable drug delivery system and evaluated the release of antibiotics
      both in vitro and in vivo. METHODS: PLGA copolymer and penicillin G sodium were
      mixed, compressed, and sintered to fabricate biodegradable antibiotic beads. The
      beads were placed in phosphate-buffered saline to test the characteristics of in
      vitro drug release. The beads then were introduced into the pleural cavities
      through chest tubes of six New Zealand white rabbits. Daily pleural effusion was
      collected to measure the antibiotic concentration and bacterial inhibitory
      characteristics. RESULTS: Forty percent of the penicillin was released in the
      first day in the in vitro study. The rest of the antibiotic was then gradually
      released in the following 30 days. All six animals survived the experiment. The
      initial surge of drug release was less significant in the pleural cavity than in
      the phosphate-buffered saline. The drug concentrations were well above the
      minimum inhibitory concentration breakpoint for penicillin susceptibility
      throughout the study period in both in vitro (30 days) and in vivo (14 days)
      studies. CONCLUSIONS: These preliminary findings demonstrated that the
      biodegradable PLGA antibiotic beads could achieve a fairly steady antibiotic
      release in the pleural cavity for at least 2 weeks. This drug delivery system may
      have the potential to serve as an adjuvant treatment of pleural cavity infection.

PMID- 21960701
TI  - Subpleural perfusion as a predictor for a poor surgical outcome in chronic
      thromboembolic pulmonary hypertension.
AB  - BACKGROUND: Small vessel disease is a major determinant of poor outcome after
      pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension
      (CTEPH). Out-of-proportion pulmonary vascular resistance (PVR) may indicate the
      presence of small vessel disease, but it is a very subjective evaluation. We
      investigated poor subpleural perfusion as a marker for small vessel disease and
      assessed its association with disease severity and surgical outcome of CTEPH.
      METHODS: We assessed the subpleural perfused area in the capillary phase of
      pulmonary angiography in 104 consecutive patients, including 45 who underwent
      surgery, and then divided the patients into either the well-perfused group (the
      subpleural space in at least one segment was well perfused [n = 75]) or the
      poorly perfused group (subpleural spaces were either unperfused or minimally
      perfused in all segments [n = 29]). We compared the pulmonary hemodynamics,
      degree of distal thrombi, and surgical outcome between these two groups. RESULTS:
      The poorly perfused group had significantly higher PVR (937 +/- 350 dyne/s/cm(5)
      vs 754 +/- 373 dyne/s/cm(5), P = .02) and more distal thrombi, resulting in fewer
      surgically treated patients (27.6% vs 49.3%, P = .04) compared with the well
      perfused group. This group showed a higher surgical mortality (62.5% vs 2.7%) and
      higher postoperative PVR (656 +/- 668 dyne/s/cm(5) vs 319 +/- 223 dyne/s/cm(5), P
      = .04). Even in a multivariate analysis, poor subpleural perfusion was associated
      with surgical mortality. CONCLUSIONS: Poor subpleural perfusion in the capillary
      phase of pulmonary angiography might be related to small vessel disease and a
      poor surgical outcome of CTEPH.

PMID- 21960702
TI  - A 32-year-old male with a 2-month history of cough, fatigue, and weight loss.

PMID- 21960703
TI  - Silent mutation in rpoB detected from clinical samples with rifampin-susceptible
      Mycobacterium tuberculosis.

PMID- 21960704
TI  - Sequence variation within the P1 gene of Mycoplasma pneumoniae.

PMID- 21960706
TI  - A comprehensive method for lipid profiling by liquid chromatography-ion cyclotron
      resonance mass spectrometry.
AB  - This work aims to combine chromatographic retention, high mass resolution and
      accuracy, MS/MS spectra, and a package for automated identification and
      quantitation of lipid species in one platform for lipidomic analysis. The
      instrumental setup elaborated comprises reversed-phase HPLC coupled to a Fourier
      transform ion cyclotron resonance mass spectrometer (LTQ-FT), and Lipid Data
      Analyzer (LDA) software. Data analysis for lipid species quantification in this
      platform is based on retention time, mass resolution of 200,000, and mass
      accuracy below 2 ppm. In addition, automatically generated MS/MS spectra provide
      structural information at molecular level. This LC/MS technology allows analyzing
      complex biological samples in a quantitative manner as shown here
      paradigmatically for murine lipid droplets having a huge surplus of
      triacylglycerol species. Chromatographic preseparation of the bulk lipid class
      alleviates the problem of ion suppression of lipid species from other classes.
      Extension of 1D to 2D chromatography is possible, yet time consuming. The
      platform affords unambiguous detection of lipid species as low as 0.10/00 within
      major lipid classes. Taken together, a novel lipidomic LC/MS platform based on
      chromatographic retention, high mass resolution and accuracy, MS/MS analysis, and
      quantitation software enables analysis of complex samples as demonstrated for
      lipid droplets.

PMID- 21960707
TI  - Assessment of Ki67 in breast cancer: recommendations from the International Ki67
      in Breast Cancer working group.
AB  - Uncontrolled proliferation is a hallmark of cancer. In breast cancer,
      immunohistochemical assessment of the proportion of cells staining for the
      nuclear antigen Ki67 has become the most widely used method for comparing
      proliferation between tumor samples. Potential uses include prognosis, prediction
      of relative responsiveness or resistance to chemotherapy or endocrine therapy,
      estimation of residual risk in patients on standard therapy and as a dynamic
      biomarker of treatment efficacy in samples taken before, during, and after
      neoadjuvant therapy, particularly neoadjuvant endocrine therapy. Increasingly,
      Ki67 is measured in these scenarios for clinical research, including as a primary
      efficacy endpoint for clinical trials, and sometimes for clinical management. At
      present, the enormous variation in analytical practice markedly limits the value
      of Ki67 in each of these contexts. On March 12, 2010, an international panel of
      investigators with substantial expertise in the assessment of Ki67 and in the
      development of biomarker guidelines was convened in London by the co-chairs of
      the Breast International Group and North American Breast Cancer Group Biomarker
      Working Party to consider evidence for potential applications. Comprehensive
      recommendations on preanalytical and analytical assessment, and interpretation
      and scoring of Ki67 were formulated based on current evidence. These
      recommendations are geared toward achieving a harmonized methodology, create
      greater between-laboratory and between-study comparability, and allow earlier
      valid applications of this marker in clinical practice.

PMID- 21960708
TI  - Predictors and outcomes of limited resection for early-stage non-small cell lung
      cancer.
AB  - BACKGROUND: Lobectomy is considered the standard treatment for early-stage non
      small cell lung cancer (NSCLC); however, more limited resections are commonly
      performed. We examined patient and surgeon factors associated with limited
      resection and compared postoperative and long-term outcomes between sublobar and
      lobar resections. METHODS: A population- and health system-based sample of
      patients newly diagnosed with stage I or II NSCLC between 2003 and 2005 in five
      geographically defined regions, five integrated health-care delivery systems, and
      15 Veterans Affairs hospitals was observed for a median of 55 months, through May
      31, 2010. Predictors of limited resection and postoperative outcomes were
      compared using unadjusted and propensity score-weighted analyses. All P values
      are from two-sided tests. RESULTS: One hundred fifty-five (23%) patients
      underwent limited resection and 524 (77%) underwent lobectomy. In adjusted
      analyses of patient-specific factors, smaller tumor size (P = .004), coverage by
      Medicare or Medicaid, no insurance or unknown insurance (P = .02), more severe
      lung disease (P < .001), and a history of stroke (P = .049) were associated with
      receipt of limited resection. In adjusted analyses of surgeon characteristics,
      thoracic surgery specialty (P = .02), non-fee-for-service compensation (P =
      .008), and National Cancer Institute cancer center designation (P = .006) were
      associated with higher odds of limited resection. Unadjusted 30-day mortality was
      higher with limited resection than with lobectomy (7.1% vs 1.9%, difference =
      5.2%, 95% confidence interval [CI] = 1.5% to 10.8%, P = .003), and the adjusted
      difference was not statistically significant (6.5% vs 2.9%, difference = 3.6%,
      95% CI = -.1% to 9.2%, P = .09). Postoperative complications did not differ by
      type of surgery (all P > .05). Over the course of the study, a non-statistically
      significant trend toward improved long-term survival was evident for lobectomy,
      compared with limited resection, in adjusted analyses (hazard ratio of death =
      1.35 for limited resection, 95% CI = 0.99 to 1.84, P = .05). CONCLUSIONS:
      Evidence is statistically inconclusive but suggestive that lobectomy, compared
      with limited resection, is associated with increased long-term survival for early
      stage lung cancer. Clinical, socioeconomic, and surgeon factors appear to be
      associated with the choice of surgical resection.

PMID- 21960711
TI  - Intragraft cytomegalovirus protein expression is associated with reduced renal
      allograft survival.
AB  - BACKGROUND: Cytomegalovirus (CMV) infection is a risk factor for acute and
      chronic rejection of transplanted organs and is thought to mediate rejection
      indirectly. METHODS: In this retrospective observational cohort study, early- and
      end-stage biopsies from renal allografts lost because of chronic allograft
      dysfunction (n = 29) were examined for CMV antigens and DNA using
      immunohistochemistry, in situ hybridization, and real-time polymerase chain
      reaction. RESULTS: CMV immediate-early and late proteins were present in 27 (93%)
      of 29 of the end-stage chronic allograft dysfunction biopsies and in 64% of the
      corresponding early biopsies but not in pretransplant biopsies from CMV
      seronegative donors (n = 3). Graft survival time was reduced in patients with
      moderate or high CMV levels in the graft soon after transplantation compared with
      that in patients with no or low CMV levels in the graft. No significant
      difference was observed in serum creatinine obtained at the time of early
      biopsies. CONCLUSIONS: We provide evidence that intragraft CMV protein expression
      is associated with end-stage chronic renal allograft dysfunction, that intragraft
      CMV levels increase as graft function deteriorates, and that CMV protein
      expression in the grafts soon after transplant is associated with reduced graft
      survival. Thus, CMV may have a pathological role in chronic renal allograft
      dysfunction.

PMID- 21960709
TI  - Aversive olfactory learning and associative long-term memory in Caenorhabditis
      elegans.
AB  - The nematode Caenorhabditis elegans (C. elegans) adult hermaphrodite has 302
      invariant neurons and is suited for cellular and molecular studies on complex
      behaviors including learning and memory. Here, we have developed protocols for
      classical conditioning of worms with 1-propanol, as a conditioned stimulus (CS),
      and hydrochloride (HCl) (pH 4.0), as an unconditioned stimulus (US). Before the
      conditioning, worms were attracted to 1-propanol and avoided HCl in chemotaxis
      assay. In contrast, after massed or spaced training, worms were either not
      attracted at all to or repelled from 1-propanol on the assay plate. The memory
      after the spaced training was retained for 24 h, while the memory after the
      massed training was no longer observable within 3 h. Worms pretreated with
      transcription and translation inhibitors failed to form the memory by the spaced
      training, whereas the memory after the massed training was not significantly
      affected by the inhibitors and was sensitive to cold-shock anesthesia. Therefore,
      the memories after the spaced and massed trainings can be classified as long-term
      memory (LTM) and short-term/middle-term memory (STM/MTM), respectively.
      Consistently, like other organisms including Aplysia, Drosophila, and mice, C.
      elegans mutants defective in nmr-1 encoding an NMDA receptor subunit failed to
      form both LTM and STM/MTM, while mutations in crh-1 encoding the CREB
      transcription factor affected only the LTM.

PMID- 21960712
TI  - Severe viral infections and primary immunodeficiencies.
AB  - Patients with severe viral infections are often not thoroughly evaluated for
      immunodeficiencies. In this review, we summarize primary immunodeficiencies that
      predispose individuals to severe viral infections. Some immunodeficiencies
      enhance susceptibility to disease with a specific virus or family of viruses,
      whereas others predispose to diseases with multiple viruses in addition to
      disease with other microbes. Although the role of cytotoxic T cells in
      controlling viral infections is well known, a number of immunodeficiencies that
      predispose to severe viral diseases have recently been ascribed to defects in the
      Toll-like receptor-interferon signaling pathway. These immunodeficiencies are
      rare, but it is important to identify them both for prognostic information and
      for genetic counseling. Undoubtedly, additional mutations in proteins in the
      innate and adaptive arms of the immune system will be identified in the future,
      which will reveal the importance of these proteins in controlling infections
      caused by viruses and other pathogens.

PMID- 21960713
TI  - Clinical Importance of Streptococcus gallolyticus infection among colorectal
      cancer patients: systematic review and meta-analysis.
AB  - BACKGROUND: Streptococcus bovis has long been associated with colorectal cancer
      (CRC). However, not all genospecies are as closely related to CRC. With this
      systematic review, we aim to increase the awareness of the association between S.
      bovis biotype I (Streptococcus gallolyticus) and CRC and urge for uniform
      molecular microbiological classification. METHODS: In January 2011, the PubMed
      database was searched for all studies that investigated the association between
      S. bovis, infective endocarditis (IE), and CRC. A total of 191 studies were
      screened for eligibility and yielded 52 case reports and 31 case series, of which
      11 were used for meta-analysis on the association between S. bovis biotype, IE,
      and adenomas/carcinomas (CRC). RESULTS: Among the S. bovis-infected patients who
      underwent colonic evaluation, the median percentage of patients who had
      concomitant adenomas/carcinomas was 60% (interquartile range, 22%), which largely
      exceeds the disease rate reported in the general asymptomatic population. Meta
      analysis showed that patients with S. bovis biotype I infection had a strongly
      increased risk of having CRC (pooled odds ratio [OR], 7.26; 95% confidence
      interval [CI], 3.94-13.36) and IE (pooled OR, 16.61; 95% CI, 8.85-31.16),
      compared with S. bovis biotype II-infected patients. Notably, CRC occurred more
      often among patients with S. bovis IE than among patients with S. bovis infection
      at other sites (pooled OR, 3.72; 95% CI, 2.03-6.81). CONCLUSIONS: Our meta
      analysis clearly indicates that S. bovis should no longer be regarded as a single
      species in clinical practice, because S. gallolyticus (S. bovis biotype I)
      infection, in particular, has an unambiguous association with CRC.

PMID- 21960715
TI  - The effect of AIDS Clinical Trials Group Protocol 5164 on the time from
      Pneumocystis jirovecii pneumonia diagnosis to antiretroviral initiation in
      routine clinical practice: a case study of diffusion, dissemination, and
      implementation.
AB  - BACKGROUND: Diffusion, dissemination, and implementation of scientific evidence
      into routine clinical practice is not well understood. The Adult AIDS Clinical
      Trials Group (ACTG) Protocol 5164 showed that early antiretroviral therapy (ART;
      ie, within 14 days) after diagnosis of an opportunistic infection improved
      clinical outcomes, compared with later initiation. Subsequently, the San
      Francisco General Hospital (SFGH) HIV/AIDS Service performed the SFGH 5164
      Initiative to disseminate and implement the findings of ACTG 5164. METHODS: We
      evaluated patients who received a diagnosis of Pneumocystis jirovecii pneumonia
      (PCP) from 1 January 2001 through 30 March 2011. Survival analyses were used to
      assess changes in the time to initiation of ART after PCP, and logistic
      regression was used to evaluate changes in the odds of early ART (ie, within 14
      days) because of ACTG 5164 and SFGH 5164 Initiative. RESULTS: Among 162 patients,
      the adjusted hazard of ART initiation increased by 3.05 (95% confidence interval
      [CI], 1.86-5.02) after ACTG 5164 and by 4.89 (95% CI, 2.76-8.67) after the SFGH
      Initiative, compared with before ACTG 5164. When compared with before ACTG 5164,
      the proportion of patients who received ART within the 14 days after PCP
      diagnosis increased from 7.4% to 50.0% (P < .001) after ACTG 5164 and from 50.0%
      to 83.0% (P = .02) after the SFGH 5164 Initiative. CONCLUSIONS: Diffusion of
      findings from of a randomized trial changed practice at an academic medical
      center, but dissemination and implementation efforts were required to establish
      early ART at acceptable levels. Early ART initiation can be achieved in real
      world patient populations.

PMID- 21960714
TI  - Tuberculosis of the central nervous system in immunocompromised patients: HIV
      infection and solid organ transplant recipients.
AB  - Central nervous system (CNS) tuberculosis (TB) is a devastating infection with
      high rates of morbidity and mortality worldwide and may manifest as meningitis,
      tuberculoma, abscess, or other forms of disease. Immunosuppression, due to either
      human immunodeficiency virus infection or solid organ transplantation, increases
      susceptibility for acquiring or reactivating TB and complicates the management of
      underlying immunosuppression and CNS TB infection. This article reviews how
      immunosuppression alters the clinical presentation, diagnosis, treatment, and
      outcome of TB infections of the CNS.

PMID- 21960716
TI  - Reduced thymic output is a major mechanism of immune reconstitution failure in
      HIV-infected patients after long-term antiretroviral therapy.
AB  - BACKGROUND: Approximately 20% of human immunodeficiency virus type 1 (HIV-1)-
      infected adults do not normalize their CD4(+) T lymphocytes after long-term
      effective highly active antiretroviral therapy (HAART). The mechanistic basis for
      this failure is unclear. METHODS: Seventy-four patients were followed up
      regularly for 3-7 years. Patients with undetectable plasma viral load (<50
      copies/mL) for over 12 months were further classified into 2 groups: (1)
      immunological nonresponders, whose CD4(+) T-cell count was < 200/MUL or <20%
      compared with baseline; and (2) immunological responders, whose CD4(+) T-cell
      count was > 300/MUL or >30% compared with baseline. RESULTS: Compared with 17
      immunological responders, 13 immunological nonresponders had a lower magnitude of
      naive CD4(+) T-cell increase, a lower percentage of recent thymic immigrants
      (CD31(+)%), and a higher percentage of activated CD8(+) T cells. Furthermore,
      unlike CD4(+) T cells, which increased along with the decrease of viral load, the
      percentage of recent thymic immigrants (CD31(+)%) had little change in the
      majority of patients. These data were fit into a mathematical model, , from which
      we deduced that the initial rate of CD4(+) T-cell restoration is associated
      significantly with the percentage of recent thymic immigrants (CD31(+)%).
      CONCLUSIONS: Our data indicate that the failure to restore CD4(+) T-cell count
      following HAART was associated primarily with a defect in recent thymic
      immigrants, which suggests the existence of thymus exhaustion.

PMID- 21960717
TI  - Effective utilization of evolving methods for the laboratory diagnosis of
      Clostridium difficile infection.

PMID- 21960718
TI  - Emergence of an autochthonous and community-acquired NDM-1-producing Klebsiella
      pneumoniae in Europe.

PMID- 21960719
TI  - mz5: space- and time-efficient storage of mass spectrometry data sets.
AB  - Across a host of MS-driven-omics fields, researchers witness the acquisition of
      ever increasing amounts of high throughput MS data and face the need for their
      compact yet efficiently accessible storage. Addressing the need for an open data
      exchange format, the Proteomics Standards Initiative and the Seattle Proteome
      Center at the Institute for Systems Biology independently developed the mzData
      and mzXML formats, respectively. In a subsequent joint effort, they defined an
      ontology and associated controlled vocabulary that specifies the contents of MS
      data files, implemented as the newer mzML format. All three formats are based on
      XML and are thus not particularly efficient in either storage space requirements
      or read/write speed. This contribution introduces mz5, a complete
      reimplementation of the mzML ontology that is based on the efficient, industrial
      strength storage backend HDF5. Compared with the current mzML standard, this
      strategy yields an average file size reduction to ~54% and increases linear read
      and write speeds ~3-4-fold. The format is implemented as part of the ProteoWizard
      project and is available under a permissive Apache license. Additional
      information and download links are available from
      http://software.steenlab.org/mz5.

PMID- 21960720
TI  - Induced pluripotent stem cell-derived cardiomyocytes and long QT syndrome: is
      personalized medicine ready for prime time?

PMID- 21960721
TI  - MicroRNA133a: a new variable in vascular smooth muscle cell phenotypic switching.

PMID- 21960722
TI  - New perspectives on regeneration of the heart.

PMID- 21960723
TI  - Stem cells review series: an introduction.

PMID- 21960724
TI  - Biomaterials to enhance stem cell function in the heart.
AB  - Transplantation of stem cells into the heart can improve cardiac function after
      myocardial infarction and in chronic heart failure, but the extent of benefit and
      of reproducibility of this approach are insufficient. Survival of transplanted
      cells into myocardium is poor, and new strategies are needed to enhance stem cell
      differentiation and survival in vivo. In this review, we describe how
      biomaterials can enhance stem cell function in the heart. Biomaterials can mimic
      or include naturally occurring extracellular matrix and also instruct stem cell
      function in different ways. Biomaterials can promote angiogenesis, enhance
      engraftment and differentiation of stem cells, and accelerate electromechanical
      integration of transplanted stem cells. Biomaterials can also be used to deliver
      proteins, genes, or small RNAs together with stem cells. Furthermore, recent
      evidence indicates that the biophysical environment of stem cells is crucial for
      their proliferation and differentiation, as well as their electromechanical
      integration. Many approaches in regenerative medicine will likely ultimately
      require integration of molecularly designed biomaterials and stem cell biology to
      develop stable tissue regeneration.

PMID- 21960728
TI  - Pathways to the All-Volunteer Military.
AB  - OBJECTIVES: The present study investigates the role of a disadvantaged
      background, the lack of social connectedness, and behavioral problems in
      channeling young men to the opportunities of the all-volunteer military instead
      of to college and the labor market.  METHODS: Data from three waves of the
      National Longitudinal Study of Adolescent Health in the United States. The
      analytic sample consists of 6,938 white, black, and other males.  RESULTS: The
      greatest likelihood of military service versus college and the labor force occurs
      when young men of at least modest ability come from disadvantaged circumstances,
      experience minimal connectedness to others, and report a history of adolescent
      fighting.  DISCUSSION: Findings suggest the importance of access to post-high
      school education and worklife opportunities as a military service incentive for
      less advantaged young men in the all volunteer era.

PMID- 21960725
TI  - Mesenchymal stem cells: biology, pathophysiology, translational findings, and
      therapeutic implications for cardiac disease.
AB  - Mesenchymal stem cells (MSCs) are a prototypical adult stem cell with capacity
      for self-renewal and differentiation with a broad tissue distribution. Initially
      described in bone marrow, MSCs have the capacity to differentiate into mesoderm-
      and nonmesoderm-derived tissues. The endogenous role for MSCs is maintenance of
      stem cell niches (classically the hematopoietic), and as such, MSCs participate
      in organ homeostasis, wound healing, and successful aging. From a therapeutic
      perspective, and facilitated by the ease of preparation and immunologic
      privilege, MSCs are emerging as an extremely promising therapeutic agent for
      tissue regeneration. Studies in animal models of myocardial infarction have
      demonstrated the ability of transplanted MSCs to engraft and differentiate into
      cardiomyocytes and vasculature cells, recruit endogenous cardiac stem cells, and
      secrete a wide array of paracrine factors. Together, these properties can be
      harnessed to both prevent and reverse remodeling in the ischemically injured
      ventricle. In proof-of-concept and phase I clinical trials, MSC therapy improved
      left ventricular function, induced reverse remodeling, and decreased scar size.
      This article reviews the current understanding of MSC biology, mechanism of
      action in cardiac repair, translational findings, and early clinical trial data
      of MSC therapy for cardiac disease.

PMID- 21960726
TI  - Role of cardiac stem cells in cardiac pathophysiology: a paradigm shift in human
      myocardial biology.
AB  - For nearly a century, the human heart has been viewed as a terminally
      differentiated postmitotic organ in which the number of cardiomyocytes is
      established at birth, and these cells persist throughout the lifespan of the
      organ and organism. However, the discovery that cardiac stem cells live in the
      heart and differentiate into the various cardiac cell lineages has changed
      profoundly our understanding of myocardial biology. Cardiac stem cells regulate
      myocyte turnover and condition myocardial recovery after injury. This novel
      information imposes a reconsideration of the mechanisms involved in myocardial
      aging and the progression of cardiac hypertrophy to heart failure. Similarly, the
      processes implicated in the adaptation of the infarcted heart have to be
      dissected in terms of the critical role that cardiac stem cells and myocyte
      regeneration play in the restoration of myocardial mass and ventricular function.
      Several categories of cardiac progenitors have been described but, thus far, the
      c-kit-positive cell is the only class of resident cells with the biological and
      functional properties of tissue specific adult stem cells.

PMID- 21960729
TI  - Discussion Addendum for: 4-Methoxy-4'-nitrophenyl. Recent Advances in the Stille
      Biaryl Coupling Reaction and Applications in Complex Natural Products Synthesis.

PMID- 21960727
TI  - Imaging: guiding the clinical translation of cardiac stem cell therapy.
AB  - Stem cells have been touted as the holy grail of medical therapy, with promises
      to regenerate cardiac tissue, but it appears the jury is still out on this novel
      therapy. Using advanced imaging technology, scientists have discovered that these
      cells do not survive nor engraft long-term. In addition, only marginal benefit
      has been observed in large-animal studies and human trials. However, all is not
      lost. Further application of advanced imaging technology will help scientists
      unravel the mysteries of stem cell therapy and address the clinical hurdles
      facing its routine implementation. In this review, we will discuss how advanced
      imaging technology will help investigators better define the optimal delivery
      method, improve survival and engraftment, and evaluate efficacy and safety.
      Insights gained from this review may direct the development of future preclinical
      investigations and clinical trials.

PMID- 21960731
TI  - Biliobronchial fistula after liver surgery for giant hydatid cyst.
AB  - Background. Biliobronchial fistula (BBF) is a rare complication in the natural
      history of liver hydatid disease by Echinococcus granulosus. We present a case of
      BBF after resection of a giant liver hydatid cyst in a 72-year-old woman. Case
      Report. A total cystpericystectomy was done, leaving the left lateral section of
      the liver that was fixed to the diaphragm. Postoperatively, the patient developed
      obstructive jaundice. An ERCP showed an obstruction at the junction of the left
      biliary duct and the main biliary duct and contrast leak. At reoperation, the
      main duct was ischemic, likely due to torsion along its longitudinal axis. A
      hepatotomy was done at the hilar plate, and the biliary duct was dissected and
      anastomosed to a Roux-en-Y jejunal loop. She was discharged without
      complications. Five months later, the patient developed cholangitis and was
      successfully treated with antibiotics. However, she suffered repeated respiratory
      infections, and four months later she was admitted to the hospital with fever,
      cough, bilioptysis, and right lower lobe pneumonia. The diagnosis of BBF was
      confirmed with (99m)Tc Mebrofenin scintigraphy. At transhepatic cholangiography,
      bile duct dilation was seen, with a biliothoracic leak. She underwent dilatation
      of cholangiojejunostomy stricture with placement of an external-internal
      catheter. The catheter was removed 3.5 months later, and two years later the
      patient remains in very good condition. Conclusion. An indirect treatment of the
      BBF by percutaneous transhepatic dilation of the biliary stenosis avoided a more
      invasive treatment, with satisfactory outcome.

PMID- 21960732
TI  - Kinetic behavior of the reaction between hydroxyl radical and the SV40
      minichromosome.
AB  - Aqueous solutions containing the minichromosomal form of the virus SV40 and the
      radical scavenger DMSO were subjected to gamma-irradiation, and the resulting
      formation of single strand breaks (SSB) was quantified. Under the irradiation
      conditions, most SSBs were produced as a consequence of hydroxyl radical ((*)OH)
      reactions. By controlling the competition between DMSO and the viral DNA
      substrate for (*)OH, we are able to estimate the rate coefficient for the
      reaction of (*)OH with the SV40 minichromosome. The results cannot be described
      adequately by homogeneous competition kinetics, but it is possible to describe
      the rate coefficient for the reaction as a function of the scavenging capacity of
      the solution. The experimentally determined rate coefficient lies in the range
      1*10(9) - 2*10(9) L mol(-1) s(-1) at 10(7) s(-1), and increases with increasing
      scavenging capacity.

PMID- 21960733
TI  - Vaginal microbiota of healthy pregnant Mexican women is constituted by four
      Lactobacillus species and several vaginosis-associated bacteria.
AB  - OBJECTIVE: To identify the microbiota communities in the vaginal tracts of
      healthy Mexican women across the pregnancy. METHODS: Vaginal swabs were obtained
      during the prenatal visit of women from all trimesters (n = 64) of healthy
      pregnant women of Mexico City. DNA was isolated from each sample, and PCR-DGGE
      and sequencing of 16S rRNA gene fragments were used to identify the bacterial
      communities. RESULTS: 21 different microorganisms were identified in the vaginal
      samples. Lactobacillus genus was present in 98% of women studied. Four
      lactobacilli species were identified in vaginal samples. L. acidophilus was the
      predominant (78%) followed by L. iners (54%), L. gasseri (20%), and L.
      delbrueckii (6%). 17 different microorganisms related to bacterial vaginosis
      conditions were identified. Ureaplasma urealyticum was the predominant (21%)
      followed by BVAB1 (17%) and Gemella bergeriae (7.8%). CONCLUSIONS: Lactobacillus
      genus predominates in the vaginal samples of Mexican pregnant women associated
      with different microorganisms related to bacterial vaginosis conditions.

PMID- 21960734
TI  - Risk of Mortality and Life Expectancy After Spinal Cord Injury: The Role of
      Health Behaviors and Participation.
AB  - PURPOSE: To identify the relationships between health behaviors and participation
      and life expectancy after spinal cord injury (SCI), while controlling for
      biographic and injury factors.  METHODS: Data for this prospective cohort study
      were collected by mailed survey. Participants included 1,361 adults with
      traumatic SCI, 1 or more years post injury. Participants were enrolled an average
      of 9.7 years after injury, and mortality was determined at the end of 2007. There
      were 294 deaths by follow-up. Life expectancy was calculated utilizing person
      years and logistic regression.  RESULTS: When evaluating each factor while
      controlling for biographic and injury characteristics, it was found that smoking
      history, binge drinking, number of drinks consumed, and psychotropic prescription
      medication use were related to increased mortality risk, whereas exercise and
      weekly outings were associated with a lower mortality risk. In the final model,
      only smoking history, binge drinking, psychotropic prescription medication use,
      and weekly outings were predictive of mortality and life expectancy.  CONCLUSION:
      Several behaviors identified may become targets of prevention strategies to
      promote longevity, including smoking cessation, stopping binge drinking, avoiding
      overreliance on psychotropic prescription medications, and promoting daily
      activities away from home.

PMID- 21960735
TI  - The recent understanding of the neurotrophin's role in skeletal muscle
      adaptation.
AB  - This paper summarizes the various effects of neurotrophins in skeletal muscle and
      how these proteins act as potential regulators of the maintenance, function, and
      regeneration of skeletal muscle fibers. Increasing evidence suggests that this
      family of neurotrophic factors influence not only the survival and function of
      innervating motoneurons but also the development and differentiation of myoblasts
      and muscle fibers. Muscle contractions (e.g., exercise) produce BDNF mRNA and
      protein in skeletal muscle, and the BDNF seems to play a role in enhancing
      glucose metabolism and may act for myokine to improve various brain disorders
      (e.g., Alzheimer's disease and major depression). In adults with neuromuscular
      disorders, variations in neurotrophin expression are found, and the role of
      neurotrophins under such conditions is beginning to be elucidated. This paper
      provides a basis for a better understanding of the role of these factors under
      such pathological conditions and for treatment of human neuromuscular disease.

PMID- 21960737
TI  - A proteome reference map of the causative agent of melioidosis Burkholderia
      pseudomallei.
AB  - Burkholderia pseudomallei is the etiologic agent of melioidosis. Using 2DE and
      MALDI-TOF MS, we report here a proteome reference map constructed from early
      stationary phase, a bacterial adaptation process. We identified 282 protein spots
      representing 220 ORFs; many of them have been implicated in bacterial
      pathogenesis. Up to 20% of identified ORFs belong to post-translational
      modification and stress responses. The proteome reference map will support future
      analysis of the bacterial gene and environmental regulation and facilitate
      comparative proteomics with its sibling species.

PMID- 21960736
TI  - The PD-1/PD-L1 (B7-H1) pathway in chronic infection-induced cytotoxic T
      lymphocyte exhaustion.
AB  - Cytotoxic CD8 T lymphocytes (CTLs) play a pivotal role in the control of
      infection. Activated CTLs, however, often lose effector function during chronic
      infection. PD-1 receptor and its ligand PD-L1 of the B7/CD28 family function as a
      T cell coinhibitory pathway and are emerging as major regulators converting
      effector CTLs into exhausted CTLs during chronic infection with human
      immunodeficiency virus, hepatitis B virus, hepatitis C virus, and other pathogens
      capable of establishing chronic infections. Importantly, blockade of the PD-1/PD
      L1 pathway is able to restore functional capabilities to exhausted CTLs and early
      clinical trials have shown promise. Further research will reveal how chronic
      infection induces upregulation of PD-1 on CTLs and PD-L1 on antigen-presenting
      cells and other tissue cells and how the PD-1/PD-L1 interaction promotes CTLs
      exhaustion, which is crucial for developing effective prophylactic and
      therapeutic vaccination against chronic infections.

PMID- 21960738
TI  - Use of BODIPY (493/503) to visualize intramuscular lipid droplets in skeletal
      muscle.
AB  - Triglyceride storage is altered across various chronic health conditions
      necessitating various techniques to visualize and quantify lipid droplets (LDs).
      Here, we describe the utilization of the BODIPY (493/503) dye in skeletal muscle
      as a means to analyze LDs. We found that the dye was a convenient and simple
      approach to visualize LDs in both sectioned skeletal muscle and cultured adult
      single fibers. Furthermore, the dye was effective in both fixed and nonfixed
      cells, and the staining seemed unaffected by permeabilization. We believe that
      the use of the BODIPY (493/503) dye is an acceptable alternative and, under
      certain conditions, a simpler method for visualizing LDs stored within skeletal
      muscle.

PMID- 21960739
TI  - Production of a solvent, detergent, and thermotolerant lipase by a newly isolated
      Acinetobacter sp. in submerged and solid-state fermentations.
AB  - The lipase production ability of a newly isolated Acinetobacter sp. in submerged
      (SmF) and solid-state (SSF) fermentations was evaluated. The results demonstrated
      this strain as one of the rare bacterium, which is able to grow and produce
      lipase in SSF even more than SmF. Coconut oil cake as a cheap agroindustrial
      residue was employed as the solid substrate. The lipase production was optimized
      in both media using artificial neural network. Multilayer normal and full feed
      forward backpropagation networks were selected to build predictive models to
      optimize the culture parameters for lipase production in SmF and SSF systems,
      respectively. The produced models for both systems showed high predictive
      accuracy where the obtained conditions were close together. The produced enzyme
      was characterized as a thermotolerant lipase, although the organism was
      mesophile. The optimum temperature for the enzyme activity was 45 degrees C where
      63% of its activity remained at 70 degrees C after 2 h. This lipase remained
      active after 24 h in a broad range of pH (6-11). The lipase demonstrated strong
      solvent and detergent tolerance potentials. Therefore, this inexpensive lipase
      production for such a potent and industrially valuable lipase is promising and of
      considerable commercial interest for biotechnological applications.

PMID- 21960741
TI  - Antiproliferative activity of xanthones isolated from Artocarpus obtusus.
AB  - An investigation of the chemical constituents in Artocarpus obtusus species led
      to the isolation of three new xanthones, pyranocycloartobiloxanthone A (1),
      dihydroartoindonesianin C (2), and pyranocycloartobiloxanthone B (3). The
      compounds were subjected to antiproliferative assay against human promyelocytic
      leukemia (HL60), human chronic myeloid leukemia (K562), and human estrogen
      receptor (ER+) positive breast cancer (MCF7) cell lines.
      Pyranocycloartobiloxanthone A (1) consistently showed strong cytotoxic activity
      against the three cell lines compared to the other two with IC(50) values of 0.5,
      2.0 and 5.0 MUg/mL, respectively. Compound (1) was also observed to exert
      antiproliferative activity and apoptotic promoter towards HL60 and MCF7 cell
      lines at respective IC(50) values. The compound (1) was not toxic towards normal
      cell lines human nontumorigenic breast cell line (MCF10A) and human peripheral
      blood mononuclear cells (PBMCs) with IC(50) values of more than 30 MUg/mL.

PMID- 21960742
TI  - Identification, localization, and relative quantitation of pseudouridine in RNA
      by tandem mass spectrometry of hydrolysis products.
AB  - The constitutional isomers uridine (U) and pseudouridine (Psi) cannot be
      distinguished from each other by simple mass measurements of RNA or its fragments
      because the conversion of U into Psi is a "mass-silent" post-transcriptional
      modification. Here we propose a new mass spectrometry based method for
      identification, localization, and relative quantitation of Psi in RNA consisting
      of ~20 nucleotides that does not require chemical labeling. Our approach takes
      advantage of the different fragmentation behavior of uridine (N-glycosidic bond)
      and pseudouridine (C-glycosidic bond) residues in RNA upon collisionally
      activated dissociation.

PMID- 21960740
TI  - Proteomic analysis of sera from common variable immunodeficiency patients
      undergoing replacement intravenous immunoglobulin therapy.
AB  - Common variable immunodeficiency is the most common form of symptomatic primary
      antibody failure in adults and children. Replacement immunoglobulin is the
      standard treatment of these patients. By using a differential proteomic approach
      based on 2D-DIGE, we examined serum samples from normal donors and from matched,
      naive, and immunoglobulin-treated patients. The results highlighted regulated
      expression of serum proteins in naive patients. Among the identified proteins,
      clusterin/ApoJ serum levels were lower in naive patients, compared to normal
      subjects. This finding was validated in a wider collection of samples from newly
      enrolled patients. The establishment of a cellular system, based on a human
      hepatocyte cell line HuH7, allowed to ascertain a potential role in the
      regulation of CLU gene expression by immunoglobulins.

PMID- 21960743
TI  - The clinical significance of digital examination-indicated cerclage in women with
      a dilated cervix at 14 0/7-29 6/7 weeks.
AB  - OBJECTIVE: This study was to compare pregnancy outcomes between cerclage and
      expectant management in wemen with a dilated cervix. DESIGN: Retrospective
      multicenter cohort study. SETTING: Five hospitals of Catholic University Medical
      Center Network in Korea. POPULATION: A total of 173 women between 14 0/7 and 29
      6/7 weeks' gestation with cervical dilation of 1 cm or greater by digital
      examination. METHODS: Pregnancy outcomes were compared according to cerclage or
      expectant management, with the use of propensity-score matching. MAIN OUTCOME
      MEASURES: Primary outcome was time from presentation until delivery (weeks).
      Secondary outcomes were gestational age at delivery, neonatal survival,
      morbidity, preterm birth, and so on. RESULTS: Of 173 women, 116 received a
      cerclage (cerclage group), and 57 were managed expectantly without cerclage
      (expectant group). Cervical dilation at presentation, and the use of
      amniocentesis performed to exclude subclinical chorioamnionitis differed between
      two groups. In the overall matched cohort, there was significant difference in
      the time from presentation until delivery (cerclage vs. expectant group, 10.6+/
      6.2 vs. 2.9+/-3.2 weeks, p <0.0001). While there was no significant difference in
      the neonatal survival between two groups, there were lower neonatal morbidity as
      well as higher pregnancy maintenance rate at 28, 32, 34 and 37 weeks' gestation
      in the cerclage group, compared with the expectant group. CONCLUSION: This study
      suggests that digital examination-indicated cerclage appears to prolong gestation
      and decrease neonatal morbidity, compared with expectant management in women with
      cervical dilation between 14 0/7 and 29 6/7 weeks.

PMID- 21960744
TI  - A rare cause of bacteremia in a pediatric patient with Down syndrome:
      Sphingomonas paucimobilis.
AB  - Sphingomonas paucimobilis, is a yellow-pigmented, aerobic, non fermentative, gram
      negative motile bacillus. S. paucimobilis which is widely found in nature and
      hospital environments rarely cause serious or life threatening infections. In
      this report, a case of hospital acquired bloodstream infection due to S.
      paucimobilis in a patient with Down syndrome who was on treatment for presumed
      pneumonia is presented. A one year-old child patient who was a known case of Down
      syndrome and had previously experienced cardiac surgery was hospitalized and
      treated for pneumonia. On the 12th day of hospitalization, blood cultures were
      taken because of a high body temperature. One of the blood cultures was positive
      for gram-negative rods. After 48 hour of incubation, the sub-cultures on blood
      agar medium yielded pure growth of a yellow, non-fermentative, gram-negative, rod
      shaped bacterium. The microorganism was positive for oxidase, and esculin
      hydrolysis, while negative for urea and nitrate reduction, citrate utilisation
      and motility. The isolate had been identified as S. paucimobilis by using Vitek 2
      system. The antibiotic susceptibility test was also performed with the same
      system and the strain was found to be susceptible to piperacillin-tazobactam and
      other antibiotics. Treatment with intravenous piperacilin-tazobactam (150
      mg/kg/day) was initiated. He responded well to the treatment and was discharged
      after 10 days. This case is reported to emphasize that S. paucimobilis should be
      kept in mind as a nosocomial infectious agent in patients with Down syndrome and
      immunosuppressive patients and the infections should be treated according to the
      sensitivity test results.

PMID- 21960746
TI  - Iatrogenic mandibular fracture associated with third molar removal.
AB  - Third molar extraction is one of the most common procedures performed in oral and
      maxillofacial surgery units. It is sometimes accompanied by complications such as
      alveolar osteitis, secondary infection, hemorrhage, dysesthesia and, most
      severely, iatrogenic fracture. This article describes two mandibular angle
      fractures that occurred in two patients during the surgical extraction of one
      erupted and one unerupted third molar, including a brief review of the
      literature.

PMID- 21960745
TI  - Evaluation of QT and P wave dispersion and mean platelet volume among
      inflammatory bowel disease patients.
AB  - BACKGROUND: In inflammatory bowel disease (IBD) number of thromboembolic events
      are increased due to hypercoagulupathy and platelet activation. Increases in mean
      platelet volume (MPV) can lead to platelet activation, this leads to
      thromboembolic events and can cause acute coronary syndromes. In IBD patients, QT
      dispersion and P-wave dispersion are predictors of ventricular arrhythmias and
      atrial fibrilation; MPV is accepted as a risk factor for acute coronary
      syndromes, we aimed at evaluating the correlations of these with the duration of
      disease, its localization and activity. METHODS: The study group consisted of 69
      IBD (Ulcerative colitis n: 54, Crohn's Disease n: 15) patients and the control
      group included 38 healthy individuals. Disease activity was evaluated both
      endoscopically and clinically. Patients with existing cardiac conditions, those
      using QT prolonging medications and having systemic diseases, anemia and
      electrolyte imbalances were excluded from the study. QT-dispersion, P-wave
      dispersion and MPV values of both groups were compared with disease activity, its
      localization, duration of disease and the antibiotics used. RESULTS: The P-wave
      dispersion values of the study group were significantly higher than those of the
      control group. Duration of the disease was not associated with QT-dispersion, and
      MPV levels. QT-dispersion, P-wave dispersion, MPV and platelet count levels were
      similar between the active and in mild ulcerative colitis patients. QT-dispersion
      levels were similar between IBD patients and the control group. No difference was
      observed between P-wave dispersion, QT-dispersion and MPV values; with regards to
      disease duration, disease activity, and localization in the study group (p>0.05).
      CONCLUSIONS: P-wave dispersion which is accepted as a risk factor for the
      development of atrial fibirilation was found to be high in our IBD patients. This
      demonstrates us that the risk of developing atrial fibrillation may be high in
      patients with IBD. No significant difference was found in the QT-dispersion, and
      in the MPV values when compared to the control group.

PMID- 21960747
TI  - Risk factors of neonatal anemia in placenta previa.
AB  - OBJECTIVES: Placenta previa is a major cause of neonatal anemia. The purpose of
      this study was to elucidate the risk factors of neonatal anemia in placenta
      previa. METHODS: The study was conducted on 158 placenta previa patients at 3
      hospitals in affiliation with the Catholic Medical Center, Seoul, Korea from May
      1999 through December 2009. The subjects were divided in to 2 groups: 47 placenta
      previa patients with neonatal anemia, and 113 placenta previa patients without
      neonatal anemia. The subjects' characteristics were compared. Logistic regression
      was used to control for confounding factors. RESULTS: Anterior placental location
      (OR 2.48; 95% CI: 1.20-5.11) was an independent risk factor of neonatal anemia
      after controlling for potential confounders. CONCLUSION: To manage neonatal
      anemia in placenta previa patients, obstetricians should do their best to detect
      placental location. Pediatricians should consider the high possibility of
      neonatal anemia in cases involving anterior placental location.

PMID- 21960748
TI  - Multicentric epithelioid hemangioendothelioma involving the same lower extremity:
      a case report and review of literature.
AB  - Epithelioid hemangioendothelioma (EH) is an uncommon low-grade malignant soft
      tissue tumor; no case has been previously reported where multicentric epithelioid
      hemangioendothelioma occurred in the same lower extremity at different sites. We
      report a case involving the common peroneal nerve and subsequently the long bone
      and the short bones of the same lower extremity, and also review the literature.
      After establishing case of several lesions, we reviewed the histopathology
      properly and followed up the patient for a long time with serial whole body
      assessment to pick up any subsequent lesions.

PMID- 21960750
TI  - A simple automated method for the determination of nitrate and nitrite in infant
      formula and milk powder using sequential injection analysis.
AB  - A fast and efficient automated method using a sequential injection analysis (SIA)
      system, based on the Griess, reaction was developed for the determination of
      nitrate and nitrite in infant formulas and milk powder. The system enables to mix
      a measured amount of sample (previously constituted in the liquid form and
      deproteinized) with the chromogenic reagent to produce a colored substance whose
      absorbance was recorded. For nitrate determination, an on-line prereduction step
      was added by passing the sample through a Cd minicolumn. The system was
      controlled from a PC by means of a user-friendly program. Figures of merit
      include linearity (r(2) > 0.999 for both analytes), limits of detection (0.32 mg
      kg(-1) NO(3)-N, and 0.05 mg kg(-1) NO(2)-N), and precision (s(r)%) 0.8-3.0.
      Results were statistically in good agreement with those obtained with the
      reference ISO-IDF method. The sampling frequency was 30 hour(-1) (nitrate) and 80
      hour(-1) (nitrite) when performed separately.

PMID- 21960749
TI  - Atorvastatin inhibits myocardial cell apoptosis in a rat model with post
      myocardial infarction heart failure by downregulating ER stress response.
AB  - OBJECTIVE: To determine the effect of atorvastatin on rat heart failure after
      myocardial infarction and to investigate the underlying mechanism of atorvastatin
      mediated myocardium protection. METHODS: Thirty-eight rats were randomly divided
      into three groups: a heart failure model group (model group), a heart failure
      plus atorvastatin treatment group (atorvastatin group) and a sham-surgery group
      (control group). The rat heart failure model was established by ligation of the
      left anterior descending of coronary arteries (LADs). Changes in hemodynamics
      parameters were recorded after the final drug administration. Plasma brain
      natriuretic peptide (BNP) concentration was determined by enzyme-linked
      immunosorbent assay (ELISA). Histological diagnosis was achieved by hematoxylin
      and eosin (H&E) and Masson's trichrome staining. The expressions of 78 kDa
      glucose-regulated protein 78 (GRP78), caspase-12 and C/EBP homologous protein
      (CHOP, also known as GADD153) in myocardial cells and cultured cardiac myocytes
      were examined by Western blot. Terminal deoxynucleotidyl transferase dUTP nick
      end labeling (TUNEL) was used to evaluate myocardial cell apoptosis, and flow
      cytometry was performed to examine the cell apoptosis of cultured cardiac
      myocytes. RESULTS: In the atorvastatin group, myocardial cells were lined up more
      orderly and myocardial fibrosis level was decreased compared to the model group.
      The expressions of GRP78, caspase-12 and CHOP in myocardial cells were decreased
      in atorvastatin group. Moreover, in the atorvastatin-treated group the cell
      apoptosis rate was reduced and the endoplasmic reticulum (ER) stress was
      activated in response to heart failure and angiotensin II (Ang II) stimulation.
      CONCLUSIONS: By down-regulating GRP78, caspase-12 and CHOP expressions in
      myocardial cells in rat heart failure after myocardial infarction, atorvastatin
      treatment decreased the apoptosis of myocardial cells, suggesting the possible
      mechanism by which atorvastatin functions in protecting against heart failure.

PMID- 21960751
TI  - From the Editor's Desk.

PMID- 21960752
TI  - Editorial - a potential new target gene of the master-regulator microphthalmia
      associated transcription factor in melanoma.

PMID- 21960753
TI  - Overexpression of the progestagen-associated endometrial protein gene is
      associated with microphthalmia-associated transcription factor in human melanoma.
AB  - BACKGROUND: We recently reported that the progestagen-associated endometrial
      protein (PAEP) gene is overexpressed and promotes tumor proliferation and
      metastasis in human melanoma. METHODS: To identify the molecules that regulate
      its expression and oncogenic properties, we analyzed the gene microarray
      profiling of melanoma samples of serial clinical stage. RESULTS: We found that
      the expression profile of the PAEP gene parallels that of microphthalmia
      associated transcription factor (MITF, r  =  0.86), a master regulator of
      melanocyte development and melanoma progression. This parallelism was further
      confirmed with semiquantitative reverse transcriptase polymerase chain reaction
      analysis of melanoma-derived daughter cells. Transfection of melanoma cells with
      MITF small interfering RNA (siRNA) specifically diminishes PAEP gene expression,
      whereas PAEP siRNA transfection has no effect on MITF. Furthermore, knockdown of
      either the MITF or PAEP gene reveals a significant inhibition of tumor cell
      migration. CONCLUSIONS: Our data indicate that PAEP expression is regulated in
      part by MITF and may thus play a role in MITF-mediated cell migration in human
      melanoma.

PMID- 21960755
TI  - Quality of life in hypertensive clinic patients following hurricane katrina.
AB  - BACKGROUND: The purpose of this study was to assess quality of life among
      hypertensive patients in the year following Hurricane Katrina. METHODS:
      Hypertensive patients (n  =  211) in a multispecialty group practice in New
      Orleans completed validated surveys during the year after Hurricane Katrina. We
      assessed patients' demographics, quality of life (Medical Outcomes Study 36),
      hurricane coping self-efficacy, property damage, stress, and changes in distance
      from and visits with family and friends. RESULTS: The mean age of participants
      was 63.5 years, 45.0% were men, 70.6% were white, 89.5% had graduated from high
      school, and 68.3% were married. Mean quality of life scores (standard deviation)
      were physical functioning 64.6 (30.0), role physical 60.0 (42.8), bodily pain
      59.9 (24.3), general health 60.4 (20.5), vitality 53.6 (26.5), social functioning
      74.5 (28.1), role emotional 67.8 (41.1), and mental 72.3 (22.0). After adjustment
      for age, gender, and race, lower coping self-efficacy, more damage to their
      residence, higher levels of stress after the storm, increased distance from
      family and friends, and decreased visits with family and friends were associated
      with lower quality of life. Personal and financial losses were identified as the
      most common cause of postdisaster stress, reported by 29.6% of participants.
      CONCLUSIONS: Storm-related factors were associated with lower quality of life in
      adult patients with hypertension after Hurricane Katrina. Providers managing
      hypertensive patients in disaster-prone areas may want to consider these factors
      in identifying patients at risk for lower quality of life following catastrophes.

PMID- 21960754
TI  - Body composition in coronary heart disease: how does body mass index correlate
      with body fatness?
AB  - BACKGROUND: Despite its many known shortcomings, body mass index (BMI) is the
      most widely used measure of obesity, in part because of its practicality. Other
      more physiologic measurements of obesity have been proposed, including percent
      body fat (BF). Few studies have compared BMI and BF, especially in patients with
      coronary heart disease (CHD). METHODS: We studied 581 patients with CHD following
      major CHD events. We divided patients into low (<= 25% in men and <= 35% in
      women) and high BF (> 25% in men and > 35% in women) as determined by the sum of
      the skin-fold method and compared these findings with standard BMI
      determinations. RESULTS: BMI and BF were highly correlated (r  =  0.60; P < .001)
      and classified patients in the same category (obese vs nonobese) in 68% of cases.
      The agreement was optimal in the underweight (BMI < 18.5 kg/m(2)) and obese class
      II category (BMI 35-39.9 kg/m(2)), in which 100% of patients were classified as
      nonobese and obese, respectively, by both BMI and BF categories. The performance
      was worst in patients with BMIs in the overweight or preobese range (25-29.9
      kg/m(2)), in which 58% of patients would be classified as obese according to BF
      criteria. CONCLUSIONS: Although some CHD patients are classified differently by
      BMI and BF, especially within the overweight BMI group, in general BMI and BF are
      highly correlated, especially in the underweight and obese BMI groups.
      Prospective studies are needed to determine which index of obesity best predicts
      risk in primary and secondary prevention.

PMID- 21960756
TI  - Discordance between physician and patient self-rated health and all-cause
      mortality.
AB  - BACKGROUND: Self-assessments of health are a strong predictor of mortality.
      Whether self-assessment of health provides additional information beyond a
      physician's assessment is unclear. METHODS: We analyzed data on 14,530 US adults
      from the Third National Health and Nutrition Examination Survey. General self
      rated health (GSRH)-"In general, would you say your health is Excellent, Very
      Good, Good, Fair, or Poor?"-and a single question to physician examiners
      following a medical examination rating participants' health, both on a 5-point
      scale of Excellent, Very Good, Good, Fair, or Poor were assessed for the period
      1988-1994. All-cause mortality was assessed through December 31, 2006 (n  = 
      3,460 deaths). RESULTS: Agreement between participant GSRH and physician-assessed
      health was 53.8% (42.1% Excellent/Very Good, 8.7% Good, and 3.0% Fair/Poor;
      weighted Kappa statistic  =  0.20). After adjustment, participants who reported
      better GSRH compared to the physician assessment of their health experienced
      lower mortality (hazard ratio  =  0.76, 95% CI: 0.66-0.87). Also, participants
      reporting worse health than the physician assessment experienced higher mortality
      (hazard ratio  =  1.45, 95% CI 1.24-1.70). CONCLUSIONS: Individuals who reported
      worse health than was assessed by a physician had increased mortality. These
      results warrant evaluation of whether GSRH collection in the clinical setting
      improves outcomes.

PMID- 21960757
TI  - Increased collagen, per se, may not affect left ventricular function in
      spontaneously hypertensive rats.
AB  - BACKGROUND: Left ventricular fibrosis is considered to be a major participant in
      the development of cardiac dysfunction in various conditions (hypertension,
      aging, etc). Because cardiac myocytes as well as blood supply may also be
      affected in these conditions, it is difficult to define quantitatively the role
      of fibrosis. We hypothesized that by inducing myocardial collagen accumulation by
      treatment with an inhibitor (doxycycline) of matrix metalloproteinases, which by
      itself should not affect cardiac myocytes, we might examine a more specific role
      of fibrosis in cardiac dysfunction. METHODS: Adult male spontaneously
      hypertensive rats were divided into 2 groups. The control group received no
      treatment; the second group was given doxycycline (30 mg/kg/day) for 6 months.
      Arterial pressure, pulse wave velocity, indexes of heart function (end-diastolic
      pressure, maximal rates of pressure rise and fall [dP/dt(max) and dP/dt(min)],
      diastolic time constant [Tau]), weight indexes, and myocardial collagen
      concentration were determined at the end. RESULTS: The results demonstrated that
      treatment with an inhibitor of matrix metalloproteinases induced significant
      accumulation of ventricular collagen, as indicated by increased ventricular
      hydroxyproline concentration (4.71 +/- 0.12 mg/g vs 5.35 +/- 0.17 mg/g in control
      and doxycycline groups, respectively). However, arterial pressure, aortic
      stiffness (pulse wave velocity), and left ventricular function were unaffected.
      CONCLUSIONS: These findings suggest that moderate collagen accumulation does not
      by itself adversely affect cardiovascular function and that other changes in
      collagen properties (eg, formation of advanced glycation end-products) may be
      responsible for the adverse effects of myocardial fibrosis.

PMID- 21960758
TI  - Comparison of ultrasound and nerve stimulation techniques for interscalene
      brachial plexus block for shoulder surgery in a residency training environment: a
      randomized, controlled, observer-blinded trial.
AB  - BACKGROUND: The ability to provide adequate intraoperative anesthesia and
      postoperative analgesia for orthopedic shoulder surgery continues to be a
      procedural challenge. Anesthesiology training programs constantly balance the
      time needed for procedural education versus associated costs. The administration
      of brachial plexus anesthesia can be facilitated through nerve stimulation or by
      ultrasound guidance. The benefits of using a nerve stimulator include a high
      incidence of success and less cost when compared to ultrasonography. Recent
      studies with ultrasonography suggest high success rates and decreased procedural
      times, but less is known about the comparison of these procedural times in
      training programs. We conducted a prospective, randomized, observer-blinded study
      with inexperienced clinical anesthesia (CA) residents-CA-1 to CA-3-to compare
      differences in these 2 guidance techniques in patients undergoing interscalene
      brachial plexus block for orthopedic surgery. METHODS: In this study, 41 patients
      scheduled for orthopedic shoulder surgery were randomly assigned to receive an
      interscalene brachial plexus block guided by either ultrasound (US group) or
      nerve stimulation (NS group). Preoperative analgesics and sedatives were
      controlled in both groups. RESULTS: The US group required significantly less time
      to conduct the block (4.3 +/- 1.5 minutes) than the NS group (10 +/- 1.5
      minutes), P  =  .009. Moreover, the US group achieved a significantly faster
      onset of sensory block (US group, 12 +/- 2 minutes; NS group, 19 +/- 2 minutes; P
      =  .02) and motor block (US group, 13.5 +/- 2.3 minutes; NS group, 20.2 +/- 2.1
      minutes; P  =  .03). Success rates were high for both techniques and were not
      statistically different (US group, 95%; NS group, 91%). No differences were found
      in operative times, postoperative pain scores, need for rescue analgesics, or
      incidences of perioperative or postdischarge side effects. CONCLUSION: On the
      basis of our results with inexperienced residents, we found that using US in
      guiding the interscalene approach to the brachial plexus significantly shortened
      the duration of intervals in conduction of the block and onset of anesthesia when
      compared with NS; moreover, these times could have significant cost savings for
      the institution. Finally, the use of US technology in an academic medical center
      facilitates safe, cost-effective, quality care.

PMID- 21960759
TI  - Differences and similarities in the practice of medicine between australia and
      the United States of america: challenges and opportunities for the university of
      queensland and the ochsner clinical school.
AB  - BACKGROUND: In 2008, The University of Queensland (UQ) in Australia and the
      Ochsner Health System (OHS) in Louisiana entered into a partnership that will
      allow a cohort of United States (US) citizens to enroll in an Australian medical
      degree program in which students will study for their first 2 years of medical
      school in Brisbane, Australia, and then complete the final 2 years of clinical
      education at OHS in New Orleans. The program's goal is to create graduates
      eligible to practice in Australia, New Zealand, and/or the US. METHODS: We
      reviewed the UQ School of Medicine-established Ochsner Clinical School (OCS) and
      the translation of the UQ clinical curriculum to the US. RESULTS: The curriculum
      presented both challenges and opportunities, revealing the similarities and
      differences in the practice of medicine between Australia and the US. This paper
      highlights some of them, in terms of the healthcare systems, the health
      professional workforce, and medical education. For example, the healthcare system
      and medical school curriculum in Australia have a strong focus on primary care.
      CONCLUSIONS: This new model in education may help train more primary care
      physicians for the US, providing physicians with a unique global perspective to
      face the future challenges of medical practice.

PMID- 21960761
TI  - Allergic fungal rhinosinusitis: a review.
AB  - BACKGROUND: Allergic fungal rhinosinusitis (AFRS) is a relatively new and
      incompletely understood clinical entity with characteristic clinical,
      radiographic, and histopathologic findings. AFRS is often misdiagnosed.
      Recognition and understanding of this unique disease will lead to efficient
      diagnosis and treatment of this curable process. METHODS: The following is a
      review, conducted via a PubMed English language search, of the current diagnosis,
      pathogenesis, and treatment of AFRS. RESULTS: AFRS is an immune-modulated disease
      entity. The Bent and Kuhn diagnostic criteria are the standard for diagnosis of
      this disease that occurs because of an incompletely understood allergic
      mechanism. Multimodality treatment relies heavily on surgical therapy along with
      corticosteroid use and immunotherapy. CONCLUSIONS: AFRS is a unique disease
      process that differs from other forms of sinusitis and as such requires that
      physicians understand its diagnosis and management to provide care for patients
      with this condition.

PMID- 21960760
TI  - Unintended perioperative hypothermia.
AB  - BACKGROUND: Hypothermia, defined as a core body temperature less than 36 degrees
      C (96.8 degrees F), is a relatively common occurrence in the unwarmed surgical
      patient. A mild degree of perioperative hypothermia can be associated with
      significant morbidity and mortality. A threefold increase in the frequency of
      surgical site infections is reported in colorectal surgery patients who
      experience perioperative hypothermia. As part of the Surgical Care Improvement
      Project, guidelines aim to decrease the incidence of this complication. METHODS:
      We review the physiology of temperature regulation, mechanisms of hypothermia,
      effects of anesthetics on thermoregulation, and consequences of hypothermia and
      summarize recent recommendations for maintaining perioperative normothermia.
      RESULTS: Evidence suggests that prewarming for a minimum of 30 minutes may reduce
      the risk of subsequent hypothermia. CONCLUSIONS: Monitoring of body temperature
      and avoidance of unintended perioperative hypothermia through active and passive
      warming measures are the keys to preventing its complications.

PMID- 21960762
TI  - Splenic injury after colonoscopy: case report and review of literature.
AB  - BACKGROUND: Splenic injury as a result of colonoscopy is rare but may be
      underreported and cases may remain undetected. METHODS: Review of the literature
      and analysis of 93 cases, including a new case report. RESULTS: Neither a history
      of abdominal surgery nor performance of a biopsy seems related to an increased
      incidence of splenic injury. However, a number of colonoscopy-related factors,
      such as difficulty intubating, looping of the instrument, and traction on the
      splenocolic ligament, lead to capsular avulsions and lacerations of the spleen.
      In addition, excess external pressure on the left hypochondrium can simulate
      blunt trauma, and other maneuvers can increase traction at the splenic flexure.
      In the majority of cases, symptoms develop within 24 hours of the colonoscopy.
      Computed tomography scan provides the most sensitive and specific method of
      diagnosis. CONCLUSION: The number of colonoscopies continues to increase with the
      aging population, increasing the potential number of associated splenic injuries.
      The physician needs to have a high index of suspicion when a patient presents
      after colonoscopy with abdominal pain associated with hemodynamic instability.
      Abdominal pain within 24 hours is the most reliable indicator and requires
      further workup and monitoring. Persistent hemodynamic instability mandates
      operative management.

PMID- 21960764
TI  - Letters to the editor.

PMID- 21960763
TI  - Surgical management and outcome in acute ischemic colitis.
AB  - BACKGROUND: Ischemic colitis is the most common form of gastrointestinal
      ischemia. Patients usually present with abdominal discomfort and bloody diarrhea.
      Treatment is contingent on the severity of disease. Mucosal/nongangrenous
      ischemia requires only supportive measures and medical management, whereas
      transmural/gangrenous ischemia may require prompt surgical intervention. The
      purpose of this study was to review the surgical management of ischemic colitis
      in a tertiary referral center. METHODS: Retrospective chart review of patients
      with ischemic colitis managed from 1995 to 2000 at the Ochsner Foundation
      Hospital. RESULTS: Forty-eight patients were identified. Ten of these had disease
      significant enough to require surgery (21%) and are the basis of this review.
      Eight were women, and the mean age was 71.4 years (range 43-85 years).
      Distribution of the disease was the right colon in 4 cases, pancolitis in 3,
      sigmoid in 2, and the left colon in 1. Nine patients underwent bowel resection:
      primary anastomosis in 3 and creation of a stoma in the other 6 (5 ileostomies
      and 1 transverse colostomy). Follow-up ranged from 3 days to 13.8 years. One
      patient died perioperatively. CONCLUSION: Surgical management produced good
      results.

PMID- 21960765
TI  - CME Credit Information.

PMID- 21960766
TI  - CME Upcoming Events.

PMID- 21960767
TI  - CME Test/CME Application Form.

PMID- 21960769
TI  - Structure of the vesicular stomatitis virus N0-P complex.
AB  - Replication of non-segmented negative-strand RNA viruses requires the continuous
      supply of the nucleoprotein (N) in the form of a complex with the phosphoprotein
      (P). Here, we present the structural characterization of a soluble, heterodimeric
      complex between a variant of vesicular stomatitis virus N lacking its 21 N
      terminal residues (N(Delta21)) and a peptide of 60 amino acids (P(60))
      encompassing the molecular recognition element (MoRE) of P that binds RNA-free N
      (N(0)). The complex crystallized in a decameric circular form, which was solved
      at 3.0 A resolution, reveals how the MoRE folds upon binding to N and competes
      with RNA binding and N polymerization. Small-angle X-ray scattering experiment
      and NMR spectroscopy on the soluble complex confirms the binding of the MoRE and
      indicates that its flanking regions remain flexible in the complex. The structure
      of this complex also suggests a mechanism for the initiation of viral RNA
      synthesis.

PMID- 21960770
TI  - Case studies of antibiotic therapy in the management of functional
      gastrointestinal disorders.

PMID- 21960768
TI  - Comparison of N-linked Glycoproteins in Human Whole Saliva, Parotid,
      Submandibular, and Sublingual Glandular Secretions Identified using Hydrazide
      Chemistry and Mass Spectrometry.
AB  - INTRODUCTION: Saliva is a body fluid that holds promise for use as a diagnostic
      fluid for detecting diseases. Salivary proteins are known to be heavily
      glycosylated and are known to play functional roles in the oral cavity. We
      identified N-linked glycoproteins in human whole saliva, as well as the N
      glycoproteins in parotid, submandibular, and sublingual glandular fluids. 
      MATERIALS AND METHODS: We employed hydrazide chemistry to affinity enrich for N
      linked glycoproteins and glycopeptides. PNGase F releases the N-peptides/proteins
      from the agarose-hydrazide resin, and liquid chromatography-tandem mass
      spectrometry was used to identify the salivary N-glycoproteins.  RESULTS: A total
      of 156 formerly N-glycosylated peptides representing 77 unique N-glycoproteins
      were identified in salivary fluids. The total number of N-glycoproteins
      identified in the individual fluids was: 62, 34, 44, and 53 in whole saliva,
      parotid fluid, submandibular fluid, and sublingual fluid, respectively. The
      majority of the N-glycoproteins were annotated as extracellular proteins (40%),
      and several of the N-glycoproteins were annotated as membrane proteins (14%). A
      number of glycoproteins were differentially found in submandibular and sublingual
      glandular secretions.  CONCLUSIONS: Mapping the N-glycoproteome of parotid,
      submandibular, and sublingual saliva is important for a thorough understanding of
      biological processes occurring in the oral cavity and to realize the role of
      saliva in the overall health of human individuals. Moreover, identifying
      glycoproteins in saliva may also be valuable for future disease biomarker
      studies.

PMID- 21960771
TI  - Bravo pH Testing On and Off Treatment With Immediate-Release Omeprazole: A Review
      of Findings Presented at the 71st Annual Scientific Meeting of the American
      College of Gastroenterology October 20-25, 2006 Las Vegas, Nev.

PMID- 21960772
TI  - Step-up versus top-down therapy in the treatment of ulcerative colitis.

PMID- 21960773
TI  - Diagnosis and long-term management of Wilson disease.

PMID- 21960774
TI  - Diagnosis and treatment of sphincter of oddi dysfunction.

PMID- 21960775
TI  - Endoscopic treatment strategies for reflux disease.

PMID- 21960776
TI  - Best of ACG 2006: Highlights From the 71st Annual Scientific Meeting of the
      American College of Gastroenterology, October 20-25, 2006, Las Vegas, Nevada.

PMID- 21960777
TI  - Best of AASLD 2006.

PMID- 21960778
TI  - Infliximab for ulcerative colitis induction of remission and maintenance therapy.

PMID- 21960779
TI  - Refractory ulcerative colitis treatment.
AB  - Treatment of refractory ulcerative colitis (UC) is a common clinical challenge.
      In either acute or chronic refractory UC, the disease may continue to remain
      active, even though the patient is on appropriate therapy. It is important to
      reassess and characterize the patient's disease before adding new medications to
      the current medical regimen. After determining the current extent and severity of
      the UC-ruling out other causes of bloody diarrhea and determining what
      complications are present-new treatment approaches can then be started. It is
      critical to first optimize oral 5-aminosalicylic acid (5-ASA) therapy combined
      with rectal 5-ASA or corticosteroid suppositories, plus corticosteroid or 5-ASA
      enemas or foam preparations. Oral or intravenous corticosteroids are appropriate
      to use if needed, but alternative approaches must be used for long-term
      maintenance. 6-Mercaptopurine (6-MP) or azathioprine can be very helpful for
      severe chronic refractory UC. In those patients who do not respond to 5-ASA
      medications, corticosteroids, and 6-MP or azathioprine, infliximab offers an
      important approach for induction and maintenance of remission for refractory
      chronic ulcerative colitis as well as for select cases of refractory acute UC.
      Cyclosporine use is an alternative medical approach for the refractory acute UC
      patient. Colectomy with ileal pouch-anal anastomosis remains a valuable option
      for the refractory chronic or acute UC patient, because it can provide both a
      "cure" for the disease, as well as eliminate ineffective medications with their
      associated side effects.

PMID- 21960780
TI  - Progressive multifocal leukoencephalopathy with peripheral demyelinating
      neuropathy in a liver transplant patient.

PMID- 21960781
TI  - JC Virus Infection After Transplantation: Beyond the Classic Progressive
      Multifocal Leukoencephalopathy?

PMID- 21960782
TI  - Findings from the European collaborative inflammatory bowel disease database.

PMID- 21960783
TI  - Management of esophageal chest pain.

PMID- 21960784
TI  - Diagnostic and Therapeutic Applications of EUS in Pancreatic Disease.

PMID- 21960785
TI  - Terlipressin for the treatment of hepatorenal syndrome.

PMID- 21960786
TI  - Capsule endoscopy in the evaluation of obscure gastrointestinal bleeding: a
      comprehensive review.
AB  - Historically, the evaluation of patients with obscure gastrointestinal bleeding
      (OGIB) has been often suboptimal, due to the limited ability to adequately image
      the small bowel. However, over the past several years, significant improvements
      have been made in small-bowel imaging techniques, both endoscopically and
      radiologically. Since the introduction of capsule endoscopy (CE) in particular,
      the diagnostic and therapeutic approaches to OGIB have improved significantly.
      Capsule-based technology has enabled a more rapid and accurate diagnosis of many
      small-bowel disorders. Capsule endoscopy is safe and well tolerated. Many
      prospective comparative studies have shown that the diagnostic yield of CE is
      superior compared to other endoscopic and radiologic modalities. Numerous other
      studies have also shown that CE leads to a significant change in management and
      improved outcomes.

PMID- 21960787
TI  - Improvement in ulcerative colitis symptoms after use of fish oil enemas.

PMID- 21960788
TI  - Review.

PMID- 21960789
TI  - Gastro-hep news.

PMID- 21960790
TI  - Overcoming adherence issues in ulcerative colitis.
AB  - Ulcerative colitis (UC) is a chronic condition requiring lifelong medication to
      minimize the incidence of symptomatic flares. Nevertheless, studies have shown
      that a large proportion of patients are nonadherent to their prescribed
      therapeutic regimen. This review examines studies of patient adherence to 5
      aminosalicylic acid (5-ASA) therapy in real world settings and considers the
      reasons that patients do not adhere to medication. Patients offer numerous
      reasons for not taking medication as prescribed; however, neither clinical nor
      community studies have consistently identified the same groups of patients as
      being high risk for poor adherence. Indeed, the problem of nonadherence is
      complex and requires a combination of strategies to be improved. Physicians,
      physician assistants, and nurse practitioners need to take the time to explain
      the importance of continual therapy, even when patients feel well, and should
      engage patients in a discussion to aid in the understanding of their
      nonadherence. Then, healthcare providers can determine how to best amend the
      regimen to improve adherence. As taking several tablets several times daily may
      be confusing or difficult for patients, higher strength 5-ASA formulations that
      require fewer daily doses have the potential to enhance patient adherence as part
      of an overall management strategy.

PMID- 21960791
TI  - Clarifying the parameters of nonacid reflux.

PMID- 21960792
TI  - Silymarin for the treatment of chronic liver disease.

PMID- 21960793
TI  - The future use of endoscopy in therapeutic procedures.

PMID- 21960794
TI  - Prevention of postoperative Crohn's disease recurrence.

PMID- 21960795
TI  - Gastro-hep news.

PMID- 21960796
TI  - Gastric pyogenic granuloma.

PMID- 21960797
TI  - Review.

PMID- 21960799
TI  - CT Colonography: Impact of Recent Findings on the Future Practice of Colorectal
      Cancer Screening.

PMID- 21960800
TI  - Mesalamine-induced Pneumonitis and Serum Sickness-like Reaction.

PMID- 21960798
TI  - The pathophysiology of obesity and its clinical manifestations.
AB  - Obesity is an exaggeration of normal adiposity and is a central player in the
      pathophysiology of diabetes mellitus, insulin resistance, dyslipidemia,
      hypertension, and atherosclerosis, largely due to its secretion of excessive
      adipokines. Obesity is a major contributor to the metabolic dysfunction involving
      lipid and glucose, but on a broader scale, it influences organ dysfunction
      involving cardiac, liver, intestinal, pulmonary, endocrine, and reproductive
      functions. Inflammatory, insulin-resistant, hypertensive, and thrombotic
      promoting adipokines, which are atherogenic, are counterbalanced by anti
      inflammatory and anti-atherogenic adipocyte hormones such as adiponectin,
      visfatin, and acylation-stimulating protein, whereas certain actions of leptin
      and resistin are pro-atherogenic. Adiponectin is protective against liver
      fibrosis due to its anti-inflammatory effect, whereas inflammatory cytokines such
      as tumor necrosis factor-alpha are detrimental for both fatty liver and
      pancreatic insulin release. Obesity contributes to immune dysfunction from the
      effects of its inflammatory adipokine secretion and is a major risk factor for
      many cancers, including hepatocellular, esophageal, and colon. Because of the
      accelerating effects that obesity has on the worsening of metabolic syndrome and
      cancer, it has the potential to be profoundly detrimental to our species if major
      methods of prevention and/or effective treatment are not realized. It is
      essential then to institute major educational efforts aimed at promoting better
      eating habits and physical exercise.

PMID- 21960801
TI  - Is mesalamine safe?

PMID- 21960802
TI  - A large pedunculated lipoma endoscopically resected with the assistance of a
      detachable nylon endoloop.

PMID- 21960803
TI  - New endoscopic approaches to removing colonic lipomas.

PMID- 21960804
TI  - Gastro-hep news.

PMID- 21960805
TI  - Endoscopic treatments for early esophageal cancer.

PMID- 21960806
TI  - Patient Perspectives on Therapeutic Options for IBD.

PMID- 21960807
TI  - Transaminase levels and vigorous exercise.

PMID- 21960808
TI  - Competence and credentialing in endoscopy.

PMID- 21960809
TI  - New technology, new complications: pancreatitis complicating double-balloon
      enteroscopy.

PMID- 21960810
TI  - Pancreatitis, a new complication of double-balloon enteroscopy.

PMID- 21960812
TI  - Heterotopic Pancreatic Tissue Found in the Esophagus of a 14-year-old Girl.

PMID- 21960811
TI  - Screening for pancreatic cancer: current evidence and future directions.
AB  - Despite improvements in the clinical and surgical management of pancreatic
      cancer, limited strides have been made in the early detection of this highly
      lethal malignancy. The majority of localized pancreatic tumors are asymptomatic,
      and the recognized presenting symptoms of pancreatic adenocarcinoma are often
      vague and heterogeneous in nature. These factors, coupled with the lack of a
      sensitive and noninvasive screening method, have made population-based screening
      for pancreatic cancer impossible. Nevertheless, at least two large institutions
      have performed multimodality-screening protocols for individuals with high risk
      of pancreatic cancer based on genetic predisposition and strong family history.
      Abnormalities noted during these screening protocols prompted further
      investigation or surgery that resulted in the discovery of benign, potentially
      malignant, and malignant pancreatic lesions. In addition to ductal epithelial
      pancreatic intraepithelial neoplasia, greater sensitivity has recently been
      achieved in the identification and characterization of precancerous mucinous
      pancreatic tumors. Advancements in proteomics and DNA microarray technology may
      confirm serum-based biomarkers that could be incorporated into future screening
      algorithms for pancreatic cancer.

PMID- 21960813
TI  - The cantankerous pancreas.

PMID- 21960814
TI  - The role of innate immunity in Crohn's disease.

PMID- 21960815
TI  - Food bolus impaction.

PMID- 21960816
TI  - Hiatal hernia and the treatment of Acid-related disorders.

PMID- 21960817
TI  - Management of alcoholic hepatitis.

PMID- 21960818
TI  - Epstein-barr virus: an unusual cause of cholestatic hepatitis in older adults.

PMID- 21960819
TI  - Review.

PMID- 21960821
TI  - Capsule endoscopy: impact on patient management.
AB  - Capsule endoscopy (CE) is an emerging technology in the diagnosis of a variety of
      gastrointestinal (GI) disorders. However, for CE to play a significant role in
      the care of GI disease, changes in patient management and positive patient
      outcomes must be seen. The objective of this study was to determine the impact of
      CE findings in the management of patients referred for CE. The study was a
      retrospective chart review of all patients who underwent CE at the University of
      South Alabama College of Medicine from April 2002 to May 2005. Demographic data
      was collected, as well as indications for CE. Findings included active bleeding
      (some within reach of a therapeutic endoscope), masses or polyps potentially
      missed by prior evaluation, and ulcers or lesions that would require a change in
      medical or surgical management (eg, the discontinuation of medications such as
      nonsteroidal anti-inflammatory drugs [NSAIDs] or a change in inflammatory bowel
      disease [IBD] treatment regimen, based on evidence of active disease from CE). A
      total of 210 cases were reviewed in this study. Overall, CE findings would lead
      to a change in patient management in 81 of 210 patients (38.6%). When the sample
      was restricted to the 93 patients with obscure-occult bleeding, 34 patients
      (36.6%) would have a change in patient management. Of the 79 obscure-overt
      bleeding patients, 33 patients (41.8%) would experience a change in patient
      management. Of the 36 patients who had CE for known or suspected IBD, 13 patients
      (36%) would have a patient management change based on capsule findings. This
      study demonstrates that CE meets a reasonable criteria for clinical utility in
      its ability to change patient management. In our study, 36-41.8% of patients with
      suspected small-bowel disorders would experience a change in patient management
      as a result of CE. Also of importance is the ability of CE to provide information
      that reassures patients and eliminates the need for further testing.

PMID- 21960822
TI  - Small-bowel adenocarcinoma: case report and review of literature on diagnosis of
      small-bowel tumors.

PMID- 21960820
TI  - Small intestinal bacterial overgrowth: a comprehensive review.
AB  - Small intestinal bacterial overgrowth (SIBO), defined as excessive bacteria in
      the small intestine, remains a poorly understood disease. Initially thought to
      occur in only a small number of patients, it is now apparent that this disorder
      is more prevalent than previously thought. Patients with SIBO vary in
      presentation, from being only mildly symptomatic to suffering from chronic
      diarrhea, weight loss, and malabsorption. A number of diagnostic tests are
      currently available, although the optimal treatment regimen remains elusive.
      Recently there has been renewed interest in SIBO and its putative association
      with irritable bowel syndrome. In this comprehensive review, we will discuss the
      epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of
      SIBO.

PMID- 21960824
TI  - Gastro-hep news.

PMID- 21960823
TI  - Review.

PMID- 21960825
TI  - Gastro-hep news.

PMID- 21960826
TI  - The use of endoscopic ultrasound in esophageal disease.

PMID- 21960827
TI  - Current research in hepatic stem-cell function.

PMID- 21960828
TI  - Probiotic Therapies for IBD.

PMID- 21960829
TI  - Natural Orifice Transluminal Endoscopic Surgery (NOTES).

PMID- 21960830
TI  - Pediatric liver transplantation.

PMID- 21960831
TI  - Multifocal nodular nonalcoholic steatohepatitis: resolution with rosiglitazone.

PMID- 21960832
TI  - Focal Fatty liver: more than just a radiographic curiosity?

PMID- 21960833
TI  - Oral Mucosal Neuromas Leading to the Diagnosis of Multiple Endocrine Neoplasia
      Type 2B in a Child With Intestinal Pseudo-obstruction.

PMID- 21960834
TI  - Review.

PMID- 21960836
TI  - Gastro-hep news.

PMID- 21960835
TI  - Mechanism of action of ribavirin in the treatment of chronic hepatitis C.
AB  - The current standard treatment for chronic hepatitis C consists of the
      combination of pegylated interferon and ribavirin. Although interferon is known
      to have potent antiviral, immunomodulatory, and anti-inflammatory activities
      against hepatitis C, the mechanism of ribavirin action against this virus is not
      clearly understood. This article will review proposed mechanisms of ribavirin
      activity, along with their supporting data, covering ribavirin's roles in the
      direct inhibition of hepatitis C viral replication, the inhibition of inosine
      monophosphate dehydrogenase, the induction of mutagenesis to the threshold of
      error catastrophe, and immunomodulation.

PMID- 21960837
TI  - Noncardiac chest pain: current treatment.
AB  - Noncardiac chest pain (NCCP) is very common, affecting up to 25% of the adult
      population in the United States. Treatment for NCCP has markedly evolved in the
      past decade and is presently focused on gastroesophageal reflux disease (GERD)
      and visceral hypersensitivity. Aggressive treatment with proton pump inhibitors
      has become the standard of care for GERD-related NCCP. Pain modulators such as
      tricyclics, trazodone, and selective serotonin reuptake inhibitors are considered
      the mainstay of therapy for non-GERD-related NCCP Other therapeutic modalities
      such as botulinum toxin injections and hypnotherapy have demonstrated promise in
      small clinical trials.

PMID- 21960838
TI  - Preventing hepatitis B viral reactivation in patients receiving cancer
      chemotherapy.

PMID- 21960839
TI  - Performance measures and report card initiatives.

PMID- 21960840
TI  - Pill-induced esophagitis.

PMID- 21960841
TI  - Endoscopic ultrasound-guided celiac plexus neurolysis.

PMID- 21960842
TI  - Emerging diagnostic methods in inflammatory bowel disease.

PMID- 21960843
TI  - The multimatrix mesalamine formulation.

PMID- 21960844
TI  - Portal vein aneurysm: case report and review of the literature.

PMID- 21960845
TI  - Review.

PMID- 21960846
TI  - Antigliadin antibody in an ataxic patient with no other evidence of celiac sprue.

PMID- 21960847
TI  - Review.

PMID- 21960848
TI  - Pharmacogenomics of IBD Therapies.

PMID- 21960849
TI  - Inherited disorders of bile Acid transport or synthesis.

PMID- 21960850
TI  - Familial association in barrett esophagus.

PMID- 21960851
TI  - Gastro-hep news.

PMID- 21960852
TI  - Management of pancreatic ascites.

PMID- 21960853
TI  - Prospective Evaluation of FIBROSpect II for Fibrosis Detection in Hepatitis C and
      B Patients Undergoing Laparoscopic Biopsy.
AB  - Serum markers of liver fibrosis are difficult to validate, due to the sampling
      error and observer variability associated with percutaneous liver biopsies.
      Laparoscopic biopsy decreases sampling error and increases the reliability of
      histopathologic assessment. We prospectively evaluated the FIBROSpect(SM) II
      serum marker test for viral liver fibrosis against laparoscopic biopsies by
      studying 145 patients with chronic hepatitis B or C who underwent laparoscopy in
      a tertiary care setting. Serum samples obtained at biopsy were tested with
      FIBROSpect II to assess the degree of fibrosis. Multiple biopsies were obtained
      from each patient and scored blindly using the Batts-Ludwig system. An average
      biopsy stage was calculated and the performance of the test panel assessed.
      FIBROSpect II was able to rule in significant fibrosis (stages 2-4), with a
      likelihood ratio of 2.6. It correctly indicated absence of disease in 74% of
      stages 0-1 patients and correctly predicted significant disease in 67% of stages
      2-4 patients. Test correlation was highest with Batts-Ludwig stages 3 (77%) and 4
      (96%) and lowest with stage 2 (43%). Multiple biopsies from 52% of patients
      differed by at least 1 stage. In 13 patients (9%), cirrhosis was detected by
      laparoscopy but not histologically; in 4 (3%), a stage of 4 was obtained, but
      cirrhosis was not evident by laparoscopy. FIBROSpect II provided valuable
      additional information for assessing fibrosis. The discordance in fibrosis stage
      seen in multiple biopsies from the same patient underscores the need to consider
      all available information when assessing fibrosis. This study confirms and
      extends results of previous studies evaluating FIBROSpect II using percutaneous
      liver biopsy.

PMID- 21960855
TI  - Mantle-cell lymphoma in barrett esophagus.

PMID- 21960854
TI  - A multicenter retrospective experience of infliximab in Crohn's disease patients:
      infusion reaction rates and treatment persistency.
AB  - BACKGROUND: Infusion reactions have been associated with infliximab therapy, but
      no study has assessed how physicians treat and manage this common adverse event.
      GOALS: To determine how gastroenterologists manage infusion reactions, identify
      prophylactic pretreatment protocols, and determine infliximab treatment
      persistence in the presence of infusion reactions. METHOD: This retrospective
      multicenter chart review analyzed data from adults younger than 90 years at the
      time of their first infliximab infusion from 9 academic or community-based
      gastroenterology practices. Infusion reaction rates were compared using a Chi
      square test with Yates' correction. Kaplan-Meier methods assessed infliximab
      treatment persistency. RESULTS: Among 6,468 infusions with known infusion
      reaction status administered to 447 patients, 3.5% (226/6,468) of infusions
      resulted in an infusion reaction, and less than 0.1% (2/6,468) were associated
      with a serious infusion reaction. Among all patients, 19.7% (88/447) experienced
      at least 1 infusion reaction, whereas 0.4% (2/447) experienced a serious infusion
      reaction. Patients receiving concomitant immunosuppressives had fewer infusion
      reactions compared to patients not receiving them (57/322 patients, 17.7% vs
      31/125 patients, 24.8%; P=.118). The cumulative proportion of patients continuing
      infliximab therapy at 2, 4, and 5 years was 73%, 58%, and 54%, respectively.
      CONCLUSIONS: The incidence of serious infusion reactions was low. In the overall
      experience observed in this clinical practice retrospective cohort, no
      conclusions can be drawn regarding the effectiveness of specific infusion
      reaction prophylactic measures. In spite of infusion reactions, the long-term
      infliximab treatment persistence rate was high.

PMID- 21960856
TI  - Review.

PMID- 21960857
TI  - The use of endoscopic procedures in the management of celiac disease.

PMID- 21960858
TI  - The certificate of added qualification in transplant hepatology.

PMID- 21960860
TI  - Gastro-hep news.

PMID- 21960859
TI  - Management of reflux disease in elderly patients.

PMID- 21960861
TI  - Genotype/Phenotype correlations in inflammatory bowel disease.

PMID- 21960862
TI  - Clinical update: hepatitis B.
AB  - Chronic hepatitis B (CHB) remains a global health problem, with
      disproportionately high prevalence rates approaching 10-15% in the Asian
      population worldwide and in Asian immigrants in the United States. Chronic
      infection complications, including cirrhosis and hepatocellular carcinoma, occur
      in 1 5-40% of infected individuals, and important recent data from the REVEAL
      study have suggested that, independent of other factors, high viral replication
      may impact long-term disease outcomes. More recent recognition of parameters for
      defining normal transaminases may also affect decision-making for therapy
      initiation. Recently, new treatment options have been effective at viral
      suppression, with lower rates of viral resistance compared to lamivudine.
      Currently, therapies for hepatitis B treatment include interferon, lamivudine,
      adefovir, entecavir, and telbivudine. Treatment considerations need to take into
      account therapy duration and risks, specifically the development of viral
      resistance. Recently updated guidelines and algorithms use viral replication,
      alanine aminotransferase levels, and severity of histologic disease as the
      determining factors for treatment. Therapy length is dependent on hepatitis B e
      antigen (HBeAg) seroconversion in HBeAg-positive CHB patients. In patients with
      the precore/basal core promoter HBeAg-negative CHB, the treatment goal is
      continued viral suppression. Future options, including new oral agents,
      therapeutic vaccines, and combination therapies, require further study.

PMID- 21960863
TI  - Two successful pregnancies in a patient with advanced liver cirrhosis and
      hepatopulmonary syndrome.

PMID- 21960864
TI  - Review.

PMID- 21960866
TI  - Provocation of bleeding during endoscopy in patients with recurrent acute lower
      gastrointestinal bleeding.

PMID- 21960868
TI  - Optimizing the use of biologic therapies in the treatment of inflammatory bowel
      disease.

PMID- 21960867
TI  - Recurrent obscure gastrointestinal bleeding: time for provocative thinking?

PMID- 21960865
TI  - Gastrointestinal issues in the assessment and management of the obese patient.
AB  - As the obesity epidemic spreads across the world, physicians of all specialties
      will be called on to participate in the management of this condition.
      Gastroenterologists are no exception and can expect, in the future, to play a
      major role in all aspects of the care of the obese patient. Thus,
      gastroenterologists must learn to recognize, prevent, and treat gastrointestinal
      disorders related to obesity, and they must have an understanding of the risks
      and benefits of various management strategies. Gastroenterologists may also be
      called upon to assist in the evaluation and management of liver and
      gastrointestinal problems that have developed following bariatric surgery. When
      treating these problems, a thorough understanding of the anatomic and physiologic
      perturbations associated with a given procedure is essential, as is the knowledge
      of which complications are linked to weight loss and which are linked to a
      specific surgical approach.

PMID- 21960869
TI  - Emerging agents for the medical therapy of hepatocellular carcinoma.

PMID- 21960870
TI  - Management of nighttime gastroesophageal reflux disease.

PMID- 21960872
TI  - Best of DDW 2007: Highlights From Digestive Disease Week and the 108th Annual
      Meeting of the American Gastroenterological Association Institute, May 19-24,
      2007, Washington, DC.

PMID- 21960871
TI  - Colonoscopy withdrawal times and adenoma detection rates.

PMID- 21960873
TI  - How to Review a Meta-analysis.
AB  - Meta-analysis is a systematic review of a focused topic in the literature that
      provides a quantitative estimate for the effect of a treatment intervention or
      exposure. The key to designing a high quality meta-analysis is to identify an
      area where the effect of the treatment or exposure is uncertain and where a
      relatively homogenous body of literature exists. The techniques used in meta
      analysis provide a structured and standardized approach for analyzing prior
      findings in a specific topic in the literature. Meta-analysis findings may not
      only be quantitative but also may be qualitative and reveal the biases,
      strengths, and weaknesses of existing studies. The results of a meta-analysis can
      be used to form treatment recommendations or to provide guidance in the design of
      future clinical trials.

PMID- 21960874
TI  - Alopecia universalis following interferon alfa-2b and ribavirin treatment for
      hepatitis C.

PMID- 21960876
TI  - Gastro-hep news.

PMID- 21960875
TI  - Review.

PMID- 21960877
TI  - Gastro-hep news.

PMID- 21960878
TI  - Complications of IBD-related Pouch Surgery.

PMID- 21960879
TI  - The role of innate immunity in chronic hepatitis C viral infection.

PMID- 21960880
TI  - Surgical options for treatment of esophageal motility disorders.

PMID- 21960881
TI  - Endoscopic options for enteral feeding.

PMID- 21960883
TI  - Choledocholithiasis mimicking sphincter of oddi dysfunction.

PMID- 21960882
TI  - Hepatitis C Virus-related Mixed Cryoglobulinemia: Pathogenesis, Clinica
      Manifestations, and New Therapies.
AB  - Within the past decade, it has been recognized that a majority of patients with
      essential mixed cryoglobulinemia (MC) are chronically infected with hepatitis C
      virus (HCV). Although the underlying mechanisms have not been fully elucidated,
      cryoglobulin formation is clearly linked to the attempt of the host to clear the
      significant quantities of virions generated daily by the chronic infection. This
      review summarizes the current understanding of the relationship between chronic
      HCV infection and the development of MC, and discusses the interaction between
      the immune system and HCV and how this interaction can lead to the development of
      lymphoproliferative disorders.

PMID- 21960884
TI  - Sphincter of oddi dysfunction: stones, spasm, or stenosis?

PMID- 21960885
TI  - Hepatitis B: the immaculate infection.

PMID- 21960886
TI  - Review.

PMID- 21960887
TI  - Researching the Role of Mycobacterium avium paratuberculosis in the Etiology of
      Crohn's Disease.

PMID- 21960888
TI  - Esophageal diverticula.

PMID- 21960889
TI  - Management of benign biliary strictures.

PMID- 21960890
TI  - Management of portal vein thrombosis.

PMID- 21960892
TI  - Narrow-band imaging: the significance of detail.

PMID- 21960891
TI  - Current Controversies in Crohn's Disease: A Roundtable Discussion of the BRIDGe
      Group.
AB  - In March 2008, a roundtable discussion was convened by the inflammatory bowel
      disease (IBD) specialist panel the BRIDGe (Building Resources and Research in IBD
      Globally) group, which consists of junior faculty gastroenterologists who have
      undergone advanced fellowship training at IBD referral centers in the United
      States, Canada, the United Kingdom, and Australia. An agenda was formulated to
      discuss three current controversies in Crohn's disease management: the role of 5
      aminosalicylates, the use of biologic combination therapy versus monotherapy, and
      the use of step-up therapy versus top-down therapy for Crohn's disease. The aim
      of the meeting was three-fold: to review the data pertaining to each topic; to
      collect opinions from the participants as to their analysis of the literature and
      their current practice; and, where possible, to formulate recommendations of
      current best practice given the available evidence. This manuscript summarizes
      the discussions on these three areas of controversy in the current management of
      Crohn's disease.

PMID- 21960893
TI  - The significance of detail: narrow-band imaging or awareness of the endoscopist?

PMID- 21960895
TI  - Gallbladder cancer: adenoma-carcinoma or dysplasia-carcinoma sequence?

PMID- 21960894
TI  - Emerging therapies for chronic hepatitis C virus.
AB  - Current hepatitis C virus (HCV) therapies are associated with significant adverse
      events and less-than-ideal sustained virologic response (SVR) rates in genotype 1
      patients. The current standard of care, a combination of pegylated interferon and
      ribavirin, will likely remain a key component of the treatment regimen for years
      to come. Multiple new drugs are currently in development and are expected to be
      approved for use in the United States and/or European Union by 2011 at the
      earliest. Future therapies will include novel interferons, ribavirin analogues,
      NS3 HCV protease inhibitors, NS5b HCV polymerase inhibitors, cyclophilin
      inhibitors, and other novel agents. There is hope that multiple new drugs will be
      approved over the following 4-10 years to provide alternative treatment choices,
      improved SVR rates, and reductions in adverse events. However, a number of
      barriers must be overcome prior to the acceptance of these drugs, involving, but
      not limited to, their toxicity, viral resistance, optimal dose, duration, and
      their efficacy and safety in patients with unmet needs.

PMID- 21960896
TI  - Gallbladder cancer: the basics.

PMID- 21960897
TI  - Capsule endoscopy in the evaluation of small-bowel inflammation.

PMID- 21960898
TI  - Eosinophilic esophagitis in children and adults.

PMID- 21960899
TI  - The growing epidemic of hepatocellular carcinoma.

PMID- 21960900
TI  - Quality measurements in endoscopy.

PMID- 21960901
TI  - Primary gastric melanoma: a rare cause of upper gastrointestinal bleeding.

PMID- 21960902
TI  - Review.

PMID- 21960904
TI  - Gastrointestinal stromal tumor in association with pyogenic liver abscess.

PMID- 21960903
TI  - Management of fecal incontinence.
AB  - Fecal incontinence is a common condition that often impairs quality of life. It
      is generally caused by a variety of conditions that are associated with anorectal
      sensorimotor dysfunction and/or diarrhea. A detailed characterization of
      symptoms, particularly bowel habits, is useful for assessing symptom severity and
      guiding management. A careful digital rectal examination is invaluable for
      gauging anal resting and squeeze pressures and anorectal evacuation. Tests should
      be tailored to age, symptom severity, and response to previous therapy. Anorectal
      manometry and sphincter imaging are useful starting tests. Depending upon the
      clinical circumstances, additional testing and therapeutic options may be useful.
      Fecal continence can be improved by measures to regulate bowel habits and pelvic
      floor retraining. Surgical repair of anal sphincter defects improves fecal
      continence in the short but not in the long term. Newer surgical therapies and
      devices are of limited and/or unproven utility.

PMID- 21960905
TI  - Pyogenic liver abscess and silent pathologies of the digestive tract.

PMID- 21960906
TI  - Prophylactic pancreatic duct stents.

PMID- 21960907
TI  - Weighing the option of surgical therapy in the treatment of gastroesophageal
      reflux.

PMID- 21960908
TI  - Current and future therapy for primary sclerosing cholangitis.

PMID- 21960909
TI  - Gastro-hep news.

PMID- 21960910
TI  - Managing Reduced Fecundity Following IBD-related Surgery.

PMID- 21960911
TI  - 2008 gastrointestinal cancers symposium: highlights from the 2008
      gastrointestinal cancers symposium, january 25-27, 2008, orlando, fla.

PMID- 21960912
TI  - HIV/AIDS and Colorectal Cancer: A Review in the Era of Antiretrovirals.
AB  - Since the discovery of HIV/AIDS and the introduction of antiretroviral therapy,
      there have been many observations regarding the causes of HIV/AIDS deaths,
      opportunistic infections, and coexisting diseases such as non-AIDS-defining
      malignancies. The bulk of the literature worldwide has been epidemiologic and has
      involved cross-linkage of both HIV/AIDS and cancer registries. Prior
      retrospective studies have also utilized death certificates. Initial large-scale
      studies have not identified an increased risk of colon cancer in the HIV/AIDS
      population, and scrutiny of the literature has elucidated major limitations, most
      notably the lack of screening data. Only recently have there been studies
      addressing the rate of colon cancer screening in the HIV/AIDS population. There
      have also been reports suggesting an elevated risk and earlier age of onset of
      colonic neoplasia in the HIV/AIDS population. This review summarizes literature
      from the last two decades regarding HIV/AIDS and colorectal cancer and endeavors
      to stimulate interest in further investigation of a possible association.

PMID- 21960913
TI  - Iatrogenic esophageal foreign body after motor vehicle accident.

PMID- 21960914
TI  - Clinical recognition and endoscopic retrieval of misplaced endotracheal tubes.

PMID- 21960916
TI  - Natalizumab for Moderate-to-Severe Crohn's Disease.

PMID- 21960917
TI  - New endoscopic techniques for detecting dysplasia in barrett esophagus.

PMID- 21960915
TI  - Botulinum toxin and gastrointestinal tract disorders: panacea, placebo, or
      pathway to the future?
AB  - The history of botulinum toxin is fascinating. First recognized as the cause of
      botulism nearly 200 years ago, it was originally feared as a deadly poison. Over
      the last 30 years, however, botulinum toxin has been transformed into a readily
      available medication used to treat a variety of medical disorders. Interest in
      the use of botulinum toxin has been particularly strong for patients with spastic
      smooth muscle disorders of the gastrointestinal tract. Patients with achalasia,
      diffuse esophageal spasm, gastroparesis, sphincter of Oddi dysfunction, and anal
      fissures have all been treated with botulinum toxin injections, often with
      impressive results. However, not all patients respond to botulinum toxin therapy,
      and large randomized controlled trials are lacking for many conditions commonly
      treated with botulinum toxin. This paper reviews the history, microbiology, and
      pharmacology of botulinum toxin, discusses its mechanism of action, and then
      presents recent evidence from the literature regarding the use of botulinum toxin
      for the treatment of a variety of gastrointestinal tract disorders.

PMID- 21960918
TI  - Gastro-hep news.

PMID- 21960919
TI  - Certolizumab Pegol for Moderate-to-Severe Crohn's Disease.

PMID- 21960920
TI  - The SpyGlass(r) Direct Visualization System for Cholangioscopy.

PMID- 21960921
TI  - Gastroduodenal intussusception secondary to a giant brunner gland hamartoma.

PMID- 21960922
TI  - Brunner gland hamartoma.

PMID- 21960923
TI  - Management of cardio-fundal gastric varices.

PMID- 21960924
TI  - Emerging data in the concomitant use of immunomodulators and biologic therapies.

PMID- 21960925
TI  - Use of Powder PEG-3350 as a Sole Bowel Preparation: Clinical Case Series of 245
      Patients.
AB  - OBJECTIVE: To assess the efficacy of low-volume powder polyethylene glycol (PEG)
      3350 as a sole bowel preparation for colonoscopy. METHODS: This case series
      examined 245 consecutive patients (a mixture of inpatients and outpatients
      undergoing screening colonoscopy) at a hospital endoscopy center over a 2-year
      period. The patients received powder PEG-3350 in the amount of 204 g dissolved in
      32 oz of water and taken in 3 divided doses 1 hour apart with 8 oz of water in
      between each dose. Colon preparation scores (CPS) were used to assess the quality
      of colon cleansing. The results obtained from the 245 patients were collated and
      compared to those of patients receiving sodium phosphate, the historical control.
      RESULTS: The mean CPS was calculated to be 3.43, with a standard deviation of
      1.12. Of the 245 patients, 92 were scored with a grade of 4, and 5 patients had
      incomplete colonoscopies secondary to failure of bowel preparation (CPS=0). Among
      the remaining patients, 22 and 26 were graded as poor (CPS=1) or fair (CPS=2)
      bowel preparations, respectively. CONCLUSION: The low-volume powder PEG-3350
      formula used in our case series showed effective colon cleansing and may be
      considered for use as a sole bowel preparation.

PMID- 21960926
TI  - Isolated gastroduodenal Crohn's disease presenting with acute pancreatitis.

PMID- 21960927
TI  - Gastroduodenal Crohn's disease and pancreatitis.

PMID- 21960928
TI  - Bread bag clip ingestion: a rare cause of upper gastrointestinal bleeding.

PMID- 21960929
TI  - Bread bag clip: kitchen aid or gastrointestinal barricade?

PMID- 21960931
TI  - GASTRO-HEP News.

PMID- 21960930
TI  - Use of allopurinol to optimize thiopurine immunomodulator efficacy in
      inflammatory bowel disease.
AB  - The thiopurine immunomodulators azathioprine and 6-mercaptopurine are integral to
      the management of inflammatory bowel disease (IBD), particularly as
      corticosteroid-sparing and maintenance agents; however, up to 50% of patients do
      not adequately respond to these agents. Advances in pharmacogenomics and an
      increased understanding of thiopurine metabolism have led to the practice of
      measuring the thiopurine metabolites 6-thioguanine (6-TGN) and 6
      methylmercaptopurine (6-MMP) to help achieve optimal immunomodulator dosages.
      Metabolite profiles are also useful for categorizing the reasons for thiopurine
      treatment failures. A desirable metabolite profile favors 6-TGN production over 6
      MMP formation; however, a significant subgroup of IBD patients, perhaps 15%,
      preferentially metabolizes thiopurines toward the inefficacious and potentially
      hepatotoxic metabolite 6-MMP. The xanthine oxidase inhibitor allopurinol has been
      shown recently to advantageously switch thiopurine metabolism toward 6-TGN
      production in this subgroup of patients, and small studies have shown this switch
      to be safe and clinically beneficial. This article reviews evidence describing
      the use of allopurinol to optimize immunomodulator metabolism, provides careful
      practice guidelines to clinicians considering this strategy, and briefly
      discusses the potential mechanisms by which this favorable interaction occurs.

PMID- 21960932
TI  - Endoscopic ultrasound in the evaluation of adrenal masses.

PMID- 21960933
TI  - Serologic markers of hepatic fibrosis.

PMID- 21960934
TI  - Esophageal foreign bodies and food impactions.

PMID- 21960935
TI  - Emerging Strategies in the Use of IBD-related Serologic Markers.

PMID- 21960937
TI  - Severe insulin resistance in a treatment-naive chronic hepatitis C patient.

PMID- 21960936
TI  - The diagnosis and management of erythropoietic protoporphyria.
AB  - Porphyrias are a group of metabolic disorders resulting from enzymatic defects in
      the heme biosynthetic pathway. Erythropoietic protoporphyria is thought to be the
      second most common porphyria seen in clinical practice. It is, however, commonly
      under-recognized and can lead to both cutaneous manifestations as well as
      derangement in hepatic function in a minority of patients. This review summarizes
      the current understanding of this disorder. Different treatment options are
      discussed with the goal of preventing liver damage. The roles of liver and bone
      marrow transplantation are also addressed.

PMID- 21960938
TI  - Hepatitis C virus and insulin resistance/diabetes mellitus.

PMID- 21960939
TI  - The relationship between obesity and functional gastrointestinal disorders:
      causation, association, or neither?
AB  - It is possible that functional gastrointestinal disorders (FGIDs) and obesity
      have more in common than merely sharing high population prevalence. Epidemiologic
      data indicate that obesity is associated with chronic gastrointestinal
      complaints, many of which overlap with FGIDs such as irritable bowel syndrome or
      dyspepsia. This raises the possibility that obesity and FGIDs may be
      mechanistically linked. In this paper, we review and summarize the literature
      linking obesity and FGIDs, comment on the clinical relevancy of existing data,
      and suggest next steps for future research in this field.

PMID- 21960940
TI  - Primary sclerosing cholangitis in association with multiple myeloma.

PMID- 21960941
TI  - Review.

PMID- 21960942
TI  - Critical Property in Relaxor-PbTiO(3) Single Crystals --- Shear Piezoelectric
      Response.
AB  - The shear piezoelectric behavior in relaxor-PbTiO(3) (PT) single crystals is
      investigated in regard to crystal phase. High levels of shear piezoelectric
      activity, d(15) or d(24) >2000 pC N(-1), has been observed for single domain
      rhombohedral (R), orthorhombic (O) and tetragonal (T) relaxor-PT crystals. The
      high piezoelectric response is attributed to a flattening of the Gibbs free
      energy at compositions proximate to the morphotropic phase boundaries, where the
      polarization rotation is easy with applying perpendicular electric field. The
      shear piezoelectric behavior of pervoskite ferroelectric crystals was discussed
      with respect to ferroelectric-ferroelectric phase transitions and dc bias field
      using phenomenological approach. The relationship between single domain shear
      piezoelectric response and piezoelectric activities in domain engineered
      configurations were given in this paper. From an application viewpoint, the
      temperature and ac field drive stability for shear piezoelectric responses are
      investigated. A temperature independent shear piezoelectric response (d(24), in
      the range of -50 degrees C to O-T phase transition temperature) is
      thermodynamically expected and experimentally confirmed in orthorhombic relaxor
      PT crystals; relatively high ac field drive stability (5 kV cm(-1)) is obtained
      in manganese modified relaxor-PT crystals. For all thickness shear vibration
      modes, the mechanical quality factor Qs are less than 50, corresponding to the
      facilitated polarization rotation.

PMID- 21960943
TI  - Eosinophilic enteritis confined to an ileostomy site.
AB  - Eosinophilic enteritis is a rather rare condition that can manifest anywhere from
      esophagus to rectum. Its description in the literature is sparse, but
      associations have been made with collagen vascular disease, malignancy, food
      allergy, parasitic or viral infections, inflammatory bowel disease, and drug
      sensitivity. We present the case of a 41-year-old male diagnosed with ulcerative
      colitis who underwent proctocolectomy with ileal pouch anal anastomosis and loop
      ileostomy formation utilizing Seprafilm(r), who later developed eosinophilic
      enteritis of the loop ileostomy site. This is the first report of eosinophilic
      enteritis and its possible link to the use of bioabsorbable adhesion barriers.

PMID- 21960944
TI  - Primary aortodigestive fistula: a rare and potentially lethal cause of
      gastrointestinal hemorrhage.
AB  - Primary aortodigestive fistulas (PAFs) are a rare cause of gastrointestinal
      bleeding, with an incidence of 0.04-0.07% in autopsy series. The diagnosis of PAF
      is difficult and should be considered in patients with gastrointestinal
      hemorrhage of obscure origin. Because of its high mortality rate, clinical
      recognition of prodromal symptoms for early diagnosis is crucial for effective
      treatment. We report on the case of a 79-year-old patient with a PAF who was
      admitted for hematochezia and melena. The PAF was suspected during upper
      gastrointestinal endoscopy and confirmed by CT angiography.

PMID- 21960945
TI  - Endoscopic therapy of colonic liver flexure mucocele.
AB  - Colorectal mucoceles usually arise in the appendix, and colonic disease is very
      rare. We report the first case of a mucocele of the colonic liver flexure that
      was treated successfully with endoscopy. A 36-year-old man was admitted to our
      hospital because of abdominal distension persisting for 3 days. Colonoscopic
      examination revealed a round polyp in the hepatic flexure, and we performed hot
      snare polypectomy with argon plasma coagulation. Histologically, the polypectomy
      specimen was confirmed to be a mucocele, with no neoplastic changes. Follow-up
      examinations at 6 and 12 months showed no evidence of recurrence.

PMID- 21960946
TI  - Acute Renal Failure in Association with Community-Acquired Clostridium difficile
      Infection and McKittrick-Wheelock Syndrome.
AB  - We report the case of a 65-year-old Caucasian woman who experienced two separate
      episodes of acute renal failure within an 18-month period, both requiring
      emergency admission and complicated treatment. Each episode was precipitated by
      hypovolaemia from intestinal fluid losses, but from two rare and independent
      pathologies. Her first admission was attributed to community-acquired Clostridium
      difficile-associated diarrhoea (CDAD) and was treated in the intensive therapy
      unit. She returned 18 months later with volume depletion and electrolyte
      disturbances, but on this occasion a giant hypersecretory villous adenoma of the
      rectum (McKittrick-Wheelock syndrome) was diagnosed following initial abnormal
      findings on digital rectal examination by a junior physician. Unlike hospital
      acquired C. difficile, community-acquired infection is not common, although
      increasing numbers are being reported. Whilst community-acquired CDAD can be
      severe, it rarely causes acute renal failure. This case report highlights the
      pathological mechanisms whereby C. difficile toxin and hypersecretory villous
      adenoma of the rectum can predispose to acute renal failure, as well as the
      values of thorough clinical examination in the emergency room, and early
      communication with intensivist colleagues in dire situations.

PMID- 21960947
TI  - Jejunal Diverticular Perforation due to Enterolith.
AB  - Jejunal diverticulosis is a rare entity with variable clinical and anatomical
      presentations. Although there is no consensus on the management of asymptomatic
      jejunal diverticular disease, some complications are potentially life-threatening
      and require early surgical treatment. Small bowel perforation secondary to
      jejunal diverticulitis by enteroliths is rare. The aim of this study was to
      report a case of small intestinal perforation caused by a large jejunal
      enterolith. An 86-year-old woman was admitted with signs of diffuse peritonitis.
      After initial fluid recovery the patient underwent emergency laparotomy. The
      surgery showed that she had small bowel diverticular disease, mainly localized in
      the proximal jejunum. The peritonitis was due to intestinal perforation caused by
      an enterolith 12 cm in length, localized inside one of these diverticula. The
      intestinal segment containing the perforated diverticulum with the enterolith was
      removed and an end-to-end anastomosis was done to reconstruct the intestinal
      transit. The patient recovered well and was discharged from hospital on the 5th
      postoperative day. There were no signs of abdominal pain 1 year after the
      surgical procedure. Although jejunal diverticular disease with its complications,
      such as formation of enteroliths, is difficult to suspect in patients with
      peritonitis, it should be considered as a possible source of abdominal infection
      in the elderly patient when more common diagnoses have been excluded.

PMID- 21960948
TI  - Hemosuccus Pancreaticus following a Puestow Procedure in a Patient with Chronic
      Pancreatitis.
AB  - Hemosuccus pancreaticus is an unusual cause of gastrointestinal bleeding that
      occurs as a complication of chronic or acute pancreatitis. We report a case of
      extremely acute-onset hemosuccus pancreaticus occurring in a patient with chronic
      pancreatitis over a long-term follow-up after a Puestow procedure (side-to-side
      pancreaticojejunostomy). The patient was admitted to our hospital due to severe
      anemia and tarry stools indicative of gastrointestinal bleeding. Emergent
      endoscopy, including gastrointestinal fiberscopy and colon fiberscopy, showed no
      abnormal findings. Abdominal contrast-enhanced computed tomography and
      hemorrhagic scintigraphy did not detect a hemorrhagic lesion. Although
      interventional radiology was considered for diagnosis and treatment, conservative
      therapy seemed sufficient to affect hemostasis. Two weeks later, however, acute
      intestinal bleeding with hemodynamic shock occurred, and exploration was
      performed without delay. Intraoperative endoscopy through an incision of the
      reconstructed jejunal loop in the close proximal end revealed a site of active
      bleeding from the side-to-side anastomotic pancreatic duct. Following a
      longitudinal incision of the jejunal loop, a bleeding point was sutured and
      ligated on direct inspection. The patient showed a good postoperative course.

PMID- 21960949
TI  - A case of adenomyomatous hyperplasia of the extrahepatic bile duct.
AB  - Adenomyomatous hyperplasia is rarely found in the extrahepatic bile duct. A 54
      year-old man was referred to our center with a diagnosis of extrahepatic bile
      duct stenosis which had been detected by endoscopic retrograde
      choloangiopancreatography. Abdominal computed tomography revealed thickening of
      the wall of the middle extrahepatic bile duct, however no malignant cells were
      detected by cytology. Since bile duct carcinoma could not be ruled out, we
      performed resection of the extrahepatic duct accompanied by lymph node
      dissection. Histopathologically, the lesion was diagnosed as adenomyomatous
      hyperplasia of the extrahepatic bile duct. Present and previously reported cases
      showed the difficulty of making a diagnosis of adenomyomatous hyperplasia of the
      extrahepatic bile duct preoperatively or intraoperatively. Therefore, when
      adenomyomatous hyperplasia is suspected, a radical surgical procedure according
      to malignant disease may be necessary for definitive diagnosis.

PMID- 21960950
TI  - Squamous cell carcinoma of the hilar bile duct.
AB  - We herein report a rare case of squamous cell carcinoma of the hilar bile duct. A
      66-year-old Japanese male patient was admitted to our hospital because of
      appetite loss and jaundice. Abdominal computed tomography revealed an enhanced
      mass measuring 10 * 30 mm in the hilar bile duct region. After undergoing biliary
      drainage, the patient underwent extended right hepatic lobectomy with regional
      lymph nodes dissection. The tumor had invaded the right portal vein. Therefore,
      we also performed resection and reconstruction of the portal vein.
      Histopathologically, the carcinoma cells exhibited a solid structure with
      differentiation to squamous cell carcinoma with keratinization and intercellular
      bridges. Immunohistochemical staining of the tumor cells revealed positive
      cytokeratin staining and negative CAM 5.2 staining. Based on these findings, a
      definitive diagnosis of well-differentiated squamous cell carcinoma of the hilar
      bile duct was made.

PMID- 21960951
TI  - Renal cell carcinoma with unusual metastasis to the small intestine manifesting
      as extensive polyposis: successful management with intraoperative therapeutic
      endoscopy.
AB  - We present here a rare clinical case of a 53-year-old gentleman with metastasis
      from renal cell carcinoma (RCC) to the small intestine presenting with extensive
      polyposis and massive gastrointestinal bleeding which was successfully managed
      with intraoperative endoscopic polypectomy and segmental small bowel resection.
      The patient presented with melena 2 weeks after right nephrectomy for RCC.
      Capsule endoscopy found extensive polyposis throughout the small bowel, and the
      histological features confirmed the diagnosis of metastatic RCC. The patient
      eventually underwent laparotomy with intraoperative endoscopy of the entire small
      bowel. Most of the polyps were removed by snare polypectomy. Three segments of
      the small bowel with extensive transmural involvement had to be resected with
      primary anastomosis. In the 2 months following his surgery, the patient had no
      further evidence of gastrointestinal bleeding. The decision of meticulously
      removing close to 100 polyps by intraoperative endoscopy prevented the patient
      from requiring total small bowel resection and lifelong dependence on parenteral
      nutrition. In conclusion, gastrointestinal bleeding in a patient with known RCC
      should always trigger full gastrointestinal work-up including capsule endoscopy
      and, if necessary, double balloon enteroscopy.

PMID- 21960952
TI  - Right paraduodenal hernia in an adult patient: diagnostic approach and surgical
      management.
AB  - Paraduodenal hernia, a rare congenital anomaly which arises from an error of
      rotation of the midgut, is the most common type of intraabdominal hernia. There
      are two variants, right and left paraduodenal hernia, the right being less
      common. We report the case of a 41-year-old patient with a right paraduodenal
      hernia with a 6-month history of intermittent episodes of intestinal obstruction.
      Diagnosis was established by CT scan and upper gastrointestinal series with small
      bowel follow-through. In a planned laparotomy, herniation of the small bowel
      loops through the fossa of Waldeyer was found. Division of the lateral right
      attachments of the colon opened the hernia sac widely, replacing the pre- and
      postarterial segments of the intestine in the positions they would normally
      occupy at the end of the first stage of rotation during embryonic development.
      Six months after the surgery, after an uneventful recovery, the patient remains
      free of symptoms.

PMID- 21960953
TI  - Liver Parenchyma Perforation following Endoscopic Retrograde
      Cholangiopancreatography.
AB  - Although endoscopic retrograde cholangiopancreatography (ERCP) is an effective
      modality for the diagnosis and treatment of biliary and pancreatic diseases, it
      is still related with several severe complications. We report on the case of a
      female patient who developed liver parenchyma perforation following ERCP. She
      underwent ERCP with sphincterotomy and extraction of a common bile duct stone.
      Shortly after ERCP, abdominal distension was identified. Abdominal computed
      tomography revealed intraabdominal air leakage and leakage of contrast dye
      penetrating the liver parenchyma into the space around the spleen. Since
      periampullary perforation related to sphincterotomy could not be denied, she was
      referred for immediate surgery. Obvious perforation could not be found at
      surgery. Cholecystectomy, insertion of a T tube into the common bile duct,
      placement of a duodenostomy tube and drainage of the retroperitoneum were
      performed. She did well postoperatively and was discharged home on postoperative
      day 28. In conclusion, as it is well recognized that perforation is one of the
      most serious complication related to ERCP, liver parenchyma perforation should be
      suspected as a cause.

PMID- 21960954
TI  - Rhabdomyolysis associated with fenofibrate monotherapy in a patient with chronic
      myelogenous leukemia.
AB  - Rhabdomyolysis associated with fenofibrate monotherapy is extremely rare. Here,
      we report a rare case of rhabdomyolysis of the psoas muscle in an 82-year-old man
      with chronic myelogenous leukemia (CML). He was prescribed fenofibrate because of
      a hypertriglyceridemia. The patient reported generalized muscle pain and right
      abdominal pain while receiving fenofibrate monotherapy. An abdominal computed
      tomography scan and an abdominal ultrasound showed a large and low attenuation
      and high echogenicity, respectively, in the right middle abdominal area.
      Laboratory values included a serum creatine concentration of 4.1 mg/dl and a
      creatinine phosphokinase concentration of 5,882 IU/l. During laparotomy, a large
      hematoma and necrotic mass was identified in the right psoas muscle. Histological
      examination revealed that the resected specimens were of the psoas muscle with
      irregular fiber sizes, degenerating fibers surrounding the inflammatory reaction,
      and fiber necrosis that is typical for polymyositis. Based on these findings and
      the clinical history, a diagnosis of fenofibrate-induced rhabdomyolysis was made.
      To the best of our knowledge, no patient has ever been diagnosed with fulminant
      psoas rhabdomyolysis due to a fenofibrate monotherapy. This report details the
      rare case of rhabdomyolysis in a patient with CML associated with fenofibrate
      monotherapy and offers a review of the literature.

PMID- 21960955
TI  - Chronic cough and eosinophilic esophagitis: an uncommon association.
AB  - An increasing number of children, usually with gastrointestinal symptoms, is
      diagnosed with eosinophilic esophagitis (EE), and a particular subset of these
      patients complains of airway manifestations. We present the case of a 2-year-old
      child with chronic dry cough in whom EE was found after a first diagnosis of
      gastroesophageal reflux disease (GERD) due to pathological 24-hour esophageal pH
      monitoring. Traditional allergologic tests were negative, while patch tests were
      diagnostic for cow's milk allergy. We discuss the intriguing relationship between
      GERD and EE and the use of patch test for the allergologic screening of patients.

PMID- 21960956
TI  - An individual with gastric schwannoma with pathologically malignant potential
      surviving two years after laparoscopy-assisted partial gastrectomy.
AB  - Schwannomas are a kind of neurogenic tumor. They are generally benign and
      originate primarily from the central and peripheral nerve. They rarely develop in
      the gastrointestinal tract: gastric schwannomas make up 0.2% of gastric
      neoplasms. A malignant gastric schwannoma is a comparatively rare tumor, a few
      cases have been reported until now. We present the case of a 34-year-old male
      patient diagnosed during medical examination. The patient was treated with
      surgical resection, and 2 years passed without recurrence.

PMID- 21960957
TI  - Adult Hippocampal Neurogenesis and Plasticity in the Infrapyramidal Bundle of the
      Mossy Fiber Projection: II. Genetic Covariation and Identification of Nos1 as
      Linking Candidate Gene.
AB  - The hippocampus of adult rodents harbors two systems exhibiting structural
      plasticity beyond the level of synapses and dendrites. First, the persistent
      generation of granule cells (adult neurogenesis); second, dynamic changes in the
      mossy fibers (MF), in particular in the infrapyramidal mossy fiber (IMF) tract.
      Because MFs are the axons of granule cells, the question arises whether these two
      types of plasticity are linked. In the first part of this study (Romer et al.,
      2011) we have asked how both traits are regulated in relation to each other. In
      the present part, we asked whether, besides activity-dependent co-regulation,
      there would also be signs of genetic co-regulation and co-variance. For this
      purpose we used the BXD panel of recombinant inbred strains of mice, a unique
      genetic reference population that allows genetic association studies. In 31 BXD
      strains we did not find correlations between the traits describing the volume of
      the MF subfields and measures of adult neurogenesis. When we carried out
      quantitative trait locus mapping for these traits, we found that the map for IMF
      volume showed little overlap with the maps for the other parts of the projection
      or for adult neurogenesis, suggesting that to a large degree the IMF is regulated
      independently. The highest overlapping peak in the genome-wide association maps
      for IMF volume and the number of new neurons was on distal chromosome 5 (118.3
      199.2 Mb) with an LRS score of 5.5 for IMF and 6.0 for new neurons. Within this
      interval we identified Nos1 (neuronal nitric oxide synthase) as a cis-acting
      (i.e., presumably autoregulatory) candidate gene. The expression of Nos1 is has
      been previously linked with both IMF and adult neurogenesis, supporting our
      findings. Despite explaining on its own very little of the variance in the highly
      multigenic traits studied, our results suggest Nos1 may play a part in the
      complex genetic control of adult neurogenesis and IMF morphology.

PMID- 21960958
TI  - Early Cerebral Hemodynamic, Metabolic, and Histological Changes in Hypoxic
      Ischemic Fetal Lambs during Postnatal Life.
AB  - The hemodynamic, metabolic, and biochemical changes produced during the
      transition from fetal to neonatal life may be aggravated if an episode of
      asphyxia occurs during fetal life. The aim of the study was to examine regional
      cerebral blood flow (RCBF), histological changes, and cerebral brain metabolism
      in preterm lambs, and to analyze the role of oxidative stress in the first hours
      of postnatal life following severe fetal asphyxia. Eighteen chronically
      instrumented newborn lambs were randomly assigned to either a control group or
      the hypoxic-ischemic (HI) group, in which case fetal asphyxia was induced just
      before delivery. All the animals were maintained on intermittent positive
      pressure ventilation for 3 h after delivery. During the HI insult, the injured
      group developed acidosis, hypoxia, hypercapnia, lactic acidosis, and tachycardia
      (relative to the control group), without hypotension. The intermittent positive
      pressure ventilation transiently improved gas exchange and cardiovascular
      parameters. After HI injury and during ventilatory support, there continued to be
      an increased RCBF in inner regions among the HI group, but no significant
      differences were detected in cortical flow compared to the control group. Also,
      the magnitude of the increase in TUNEL positive cells (apoptosis) and antioxidant
      enzymes, and decrease of ATP reserves was significantly greater in the brain
      regions where the RCBF was not higher. In conclusion, our findings identify early
      metabolic, histological, and hemodynamic changes involved in brain damage in
      premature asphyxiated lambs. Such changes have been described in human neonates,
      so our model could be useful to test the safety and the effectiveness of
      different neuroprotective or ventilation strategies applied in the first hours
      after fetal HI injury.

PMID- 21960959
TI  - Ephus: multipurpose data acquisition software for neuroscience experiments.
AB  - Physiological measurements in neuroscience experiments often involve complex
      stimulus paradigms and multiple data channels. Ephus (http://www.ephus.org) is an
      open-source software package designed for general-purpose data acquisition and
      instrument control. Ephus operates as a collection of modular programs, including
      an ephys program for standard whole-cell recording with single or multiple
      electrodes in typical electrophysiological experiments, and a mapper program for
      synaptic circuit mapping experiments involving laser scanning photostimulation
      based on glutamate uncaging or channelrhodopsin-2 excitation. Custom user
      functions allow user-extensibility at multiple levels, including on-line analysis
      and closed-loop experiments, where experimental parameters can be changed based
      on recently acquired data, such as during in vivo behavioral experiments. Ephus
      is compatible with a variety of data acquisition and imaging hardware. This paper
      describes the main features and modules of Ephus and their use in representative
      experimental applications.

PMID- 21960961
TI  - Male or Female? Brains are Intersex.
AB  - The underlying assumption in popular and scientific publications on sex
      differences in the brain is that human brains can take one of two forms "male" or
      "female," and that the differences between these two forms underlie differences
      between men and women in personality, cognition, emotion, and behavior.
      Documented sex differences in brain structure are typically taken to support this
      dimorphic view of the brain. However, neuroanatomical data reveal that sex
      interacts with other factors in utero and throughout life to determine the
      structure of the brain, and that because these interactions are complex, the
      result is a multi-morphic, rather than a dimorphic, brain. More specifically,
      here I argue that human brains are composed of an ever-changing heterogeneous
      mosaic of "male" and "female" brain characteristics (rather than being all "male"
      or all "female") that cannot be aligned on a continuum between a "male brain" and
      a "female brain." I further suggest that sex differences in the direction of
      change in the brain mosaic following specific environmental events lead to sex
      differences in neuropsychiatric disorders.

PMID- 21960960
TI  - Striatal signal transduction and drug addiction.
AB  - Drug addiction is a severe neuropsychiatric disorder characterized by loss of
      control over motivated behavior. The need for effective treatments mandates a
      greater understanding of the causes and identification of new therapeutic targets
      for drug development. Drugs of abuse subjugate normal reward-related behavior to
      uncontrollable drug-seeking and -taking. Contributions of brain reward circuitry
      are being mapped with increasing precision. The role of synaptic plasticity in
      addiction and underlying molecular mechanisms contributing to the formation of
      the addicted state are being delineated. Thus we may now consider the role of
      striatal signal transduction in addiction from a more integrative neurobiological
      perspective. Drugs of abuse alter dopaminergic and glutamatergic
      neurotransmission in medium spiny neurons of the striatum. Dopamine receptors
      important for reward serve as principle targets of drugs abuse, which interact
      with glutamate receptor signaling critical for reward learning. Complex networks
      of intracellular signal transduction mechanisms underlying these receptors are
      strongly stimulated by addictive drugs. Through these mechanisms, repeated drug
      exposure alters functional and structural neuroplasticity, resulting in
      transition to the addicted biological state and behavioral outcomes that typify
      addiction. Ca(2+) and cAMP represent key second messengers that initiate
      signaling cascades, which regulate synaptic strength and neuronal excitability.
      Protein phosphorylation and dephosphorylation are fundamental mechanisms
      underlying synaptic plasticity that are dysregulated by drugs of abuse. Increased
      understanding of the regulatory mechanisms by which protein kinases and
      phosphatases exert their effects during normal reward learning and the addiction
      process may lead to novel targets and pharmacotherapeutics with increased
      efficacy in promoting abstinence and decreased side effects, such as interference
      with natural reward, for drug addiction.

PMID- 21960963
TI  - A Flicker Change Detection Task Reveals Object-in-Scene Memory Across Species.
AB  - Tests of recognition memory in macaques typically assay memory for objects or
      isolated images, over time spans of seconds to hours from stimulus presentation,
      and/or require extensive training. Here, we propose a new application of the
      flicker change detection task that could measure object-in-scene memory days
      after single-trial exposures. In three experiments, participants searched for a
      changing object - or "target" - embedded within a scene as their eye movements
      were tracked. For new targets-in-scenes, the change is difficult to detect and
      requires extensive search. Once the target is found, however, the change becomes
      obvious. We reasoned that the decreased times required to find a target in a
      repeated scene would indicate memory for the target. In humans, targets were
      found faster when the targets-and-scenes were explicitly remembered than when
      they were forgotten, or had never been seen before. This led to faster repeated
      trial compared to novel-trial search times. Based solely on repeated-trial search
      times, we were able to select distributions comprised of predominantly remembered
      or predominantly forgotten trials. Macaques exhibited the same repetition effects
      as humans, suggesting that remembered trials could be dissociated from novel or
      forgotten trials using the same procedures we established in humans. Finally, an
      anterograde amnesic patient with damage that included the medial temporal lobe
      (MTL) showed no search time differences, suggesting that memory revealed through
      search times on this task requires MTL integrity. Together, these findings
      indicate that the time required to locate a changing object reveals object-in
      scene memory over long retention intervals in humans and macaques.

PMID- 21960964
TI  - Late Protein Synthesis-Dependent Phases in CTA Long-Term Memory: BDNF
      Requirement.
AB  - It has been proposed that long-term memory (LTM) persistence requires a late
      protein synthesis-dependent phase, even many hours after memory acquisition.
      Brain-derived neurotrophic factor (BDNF) is an essential protein synthesis
      product that has emerged as one of the most potent molecular mediators for long
      term synaptic plasticity. Studies in the rat hippocampus have been shown that
      BDNF is capable to rescue the late-phase of long-term potentiation as well as the
      hippocampus-related LTM when protein synthesis was inhibited. 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 delivery of BDNF reverses the deficit in CTA
      memory caused by the inhibition of IC protein synthesis due to anisomycin
      administration during early acquisition. In this work, we first analyze whether
      CTA memory storage is protein synthesis-dependent in different time windows. We
      observed that CTA memory become sensible to protein synthesis inhibition 5 and 7
      h after acquisition. Then, we explore the effect of BDNF delivery (2 MUg/2 MUl
      per side) in the IC during those late protein synthesis-dependent phases. Our
      results show that BDNF reverses the CTA memory deficit produced by protein
      synthesis inhibition in both phases. These findings support the notion that
      recurrent rounds of consolidation-like events take place in the neocortex for
      maintenance of CTA memory trace and that BDNF is an essential component of these
      processes.

PMID- 21960965
TI  - Alteration and reorganization of functional networks: a new perspective in brain
      injury study.
AB  - Plasticity is the mechanism underlying the brain's potential capability to
      compensate injury. Recently several studies have shown how functional connections
      among the brain areas are severely altered by brain injury and plasticity leading
      to a reorganization of the networks. This new approach studies the impact of
      brain injury by means of alteration of functional interactions. The concept of
      functional connectivity refers to the statistical interdependencies between
      physiological time series simultaneously recorded in various areas of the brain
      and it could be an essential tool for brain functional studies, being its
      deviation from healthy reference an indicator for damage. In this article, we
      review studies investigating functional connectivity changes after brain injury
      and subsequent recovery, providing an accessible introduction to common
      mathematical methods to infer functional connectivity, exploring their
      capabilities, future perspectives, and clinical uses in brain injury studies.

PMID- 21960962
TI  - Interpersonal stress regulation and the development of anxiety disorders: an
      attachment-based developmental framework.
AB  - Anxiety disorders represent a common but often debilitating form of
      psychopathology in both children and adults. While there is a growing
      understanding of the etiology and maintenance of these disorders across various
      research domains, only recently have integrative accounts been proposed. While
      classical attachment history has been a traditional core construct in
      psychological models of anxiety, contemporary attachment theory has the potential
      to integrate neurobiological and behavioral findings within a multidisciplinary
      developmental framework. The current paper proposes a modern attachment theory
      based developmental model grounded in relevant literature from multiple
      disciplines including social neuroscience, genetics, neuroendocrinology, and the
      study of family factors involved in the development of anxiety disorders. Recent
      accounts of stress regulation have highlighted the interplay between stress,
      anxiety, and activation of the attachment system. This interplay directly affects
      the development of social-cognitive and mentalizing capacities that are acquired
      in the interpersonal context of early attachment relationships. Early attachment
      experiences are conceptualized as the key organizer of a complex interplay
      between genetic, environmental, and epigenetic contributions to the development
      of anxiety disorders - a multifactorial etiology resulting from dysfunctional co
      regulation of fear and stress states. These risk-conferring processes are
      characterized by hyperactivation strategies in the face of anxiety. The
      cumulative allostatic load and subsequent "wear and tear" effects associated with
      hyperactivation strategies converge on the neural pathways of anxiety and stress.
      Attachment experiences further influence the development of anxiety as potential
      moderators of risk factors, differentially impacting on genetic vulnerability and
      relevant neurobiological pathways. Implications for further research and
      potential treatments are outlined.

PMID- 21960966
TI  - Stereoscopic Depth Perception during Binocular Rivalry.
AB  - When we view nearby objects, we generate appreciably different retinal images in
      each eye. Despite this, the visual system can combine these different images to
      generate a unified view that is distinct from the perception generated from
      either eye alone (stereopsis). However, there are occasions when the images in
      the two eyes are too disparate to fuse. Instead, they alternate in perceptual
      dominance, with the image from one eye being completely excluded from awareness
      (binocular rivalry). It has been thought that binocular rivalry is the default
      outcome when binocular fusion is not possible. However, other studies have
      reported that stereopsis and binocular rivalry can coexist. The aim of this study
      was to address whether a monocular stimulus that is reported to be suppressed
      from awareness can continue to contribute to the perception of stereoscopic
      depth. Our results showed that stereoscopic depth perception was still evident
      when incompatible monocular images differing in spatial frequency, orientation,
      spatial phase, or direction of motion engage in binocular rivalry. These results
      demonstrate a range of conditions in which binocular rivalry and stereopsis can
      coexist.

PMID- 21960967
TI  - All about the Money - External Performance Monitoring is Affected by Monetary,
      but Not by Socially Conveyed Feedback Cues in More Antisocial Individuals.
AB  - This study investigated the relationship between feedback processing and
      antisocial personality traits measured by the PSSI questionnaire (Kuhl and Kazen,
      1997) in a healthy undergraduate sample. While event-related potentials [feedback
      related negativity (FRN), P300] were recorded, participants encountered expected
      and unexpected feedback during a gambling task. As recent findings suggest
      learning problems and deficiencies during feedback processing in clinical
      populations of antisocial individuals, we performed two experiments with
      different healthy participants in which feedback about monetary gains or losses
      consisted either of social-emotional (facial emotion displays) or non-social cues
      (numerical stimuli). Since the FRN and P300 are both sensitive to different
      aspects of feedback processing we hypothesized that they might help to
      differentiate between individuals scoring high and low on an antisocial trait
      measure. In line with previous evidence FRN amplitudes were enhanced after
      negative and after unexpected feedback stimuli. Crucially, participants scoring
      high on antisocial traits displayed larger FRN amplitudes than those scoring low
      only in response to expected and unexpected negative numerical feedback, but not
      in response to social-emotional feedback - irrespective of expectancy. P300
      amplitudes were not modulated by antisocial traits at all, but by subjective
      reward probabilities. The present findings indicate that individuals scoring high
      on antisociality attribute higher motivational salience to monetary compared to
      emotional-social feedback which is reflected in FRN amplitude enhancement.
      Contrary to recent findings, however, no processing deficiencies concerning
      social-emotional feedback stimuli were apparent in those individuals. This
      indicates that stimulus salience is an important aspect in learning and feedback
      processes in individuals with antisocial traits which has potential implications
      for therapeutic interventions in clinical populations.

PMID- 21960969
TI  - The impact of aesthetic evaluation and physical ability on dance perception.
AB  - The field of neuroaesthetics attracts attention from neuroscientists and artists
      interested in the neural underpinnings of esthetic experience. Though less
      studied than the neuroaesthetics of visual art, dance neuroaesthetics is a
      particularly rich subfield to explore, as it is informed not only by research on
      the neurobiology of aesthetics, but also by an extensive literature on how action
      experience shapes perception. Moreover, it is ideally suited to explore the
      embodied simulation account of esthetic experience, which posits that activation
      within sensorimotor areas of the brain, known as the action observation network
      (AON), is a critical element of the esthetic response. In the present study, we
      address how observers' esthetic evaluation of dance is related to their perceived
      physical ability to reproduce the movements they watch. Participants underwent
      functional magnetic resonance imaging while evaluating how much they liked and
      how well they thought they could physically replicate a range of dance movements
      performed by professional ballet dancers. We used parametric analyses to evaluate
      brain regions that tracked with degree of liking and perceived physical ability.
      The findings reveal strongest activation of occipitotemporal and parietal
      portions of the AON when participants view movements they rate as both
      esthetically pleasing and difficult to reproduce. As such, these findings begin
      to illuminate how the embodied simulation account of esthetic experience might
      apply to watching dance, and provide preliminary evidence as to why some people
      find enjoyment in an evening at the ballet.

PMID- 21960968
TI  - Direct evidence for two different neural mechanisms for reading familiar and
      unfamiliar words: an intra-cerebral EEG study.
AB  - After intensive practice, unfamiliar letter strings become familiar words and
      reading speed increases strikingly from a slow processing to a fast and with more
      global recognition of words. While this effect has been well documented at the
      behavioral level, its neural underpinnings are still unclear. The question is how
      the brain modulates the activity of the reading network according to the novelty
      of the items. Several models have proposed that familiar and unfamiliar words are
      not processed by separate networks but rather by common regions operating
      differently according to familiarity. This hypothesis has proved difficult to
      test at the neural level because the effects of familiarity and length on reading
      occur (a) on a millisecond scale, shorter than the resolution of fMRI and (b) in
      regions which cannot be isolated with non-invasive EEG or MEG. We overcame these
      limitations by using invasive intra-cerebral EEG recording in epileptic patients.
      Neural activity (gamma-band responses, between 50 and 150 Hz) was measured in
      three major nodes of reading network - left inferior frontal, supramarginal, and
      inferior temporo-occipital cortices - while patients silently read familiar
      (words) and unfamiliar (pseudo-words) items of two lengths (short composed of one
      syllable vs. long composed of three-syllables). While all items elicited strong
      neural responses in the three regions, we found that the duration of the neural
      response increases with length only for pseudo-words, in direct relation to
      orthographic-to-phonological conversion. Our results validate at the neural level
      the hypothesis that all words are processed by a common network operating more or
      less efficiently depending on words' novelty.

PMID- 21960970
TI  - Contagious yawning and seasonal climate variation.
AB  - Recent evidence suggests that yawning is a thermoregulatory behavior. To explore
      this possibility further, the frequency of contagious yawning in humans was
      measured while outdoors in a desert climate in the United States during two
      distinct temperature ranges and seasons (winter: 22 degrees C; early summer: 37
      degrees C). As predicted, the proportion of pedestrians who yawned in response to
      seeing pictures of people yawning differed significantly between the two
      conditions (winter: 45%; summer: 24%). Across conditions yawning occurred at
      lower ambient temperatures, and the tendency to yawn during each season was
      associated with the length of time spent outside prior to being tested.
      Participants were more likely to yawn in the milder climate after spending long
      periods of time outside, while prolonged exposure to ambient temperatures at or
      above body temperature was associated with reduced yawning. This is the first
      report to show that the incidence of yawning in humans is associated with
      seasonal climate variation, further demonstrating that yawn-induced contagion
      effects can be mediated by factors unrelated to individual social characteristics
      or cognitive development.

PMID- 21960971
TI  - Practice of contemporary dance improves cognitive flexibility in aging.
AB  - As society ages and frequency of dementia increases exponentially, counteracting
      cognitive aging decline is a challenging issue for countries of the developed
      world. Previous studies have suggested that physical fitness based on
      cardiovascular and strength training helps to improve attentional control in
      normal aging. However, how motor activity based on motor-skill learning can also
      benefit attentional control with age has been hitherto a neglected issue. This
      study examined the impact of contemporary dance (CD) improvisation on attentional
      control of older adults, as compared to two other motor training programs, fall
      prevention and Tai Chi Chuan. Participants performed setting, suppressing, and
      switching attention tasks before and after 5.7-month training in either CD or
      fall prevention or Tai Chi Chuan. Results indicated that CD improved switching
      but not setting or suppressing attention. In contrast, neither fall prevention
      nor Tai Chi Chuan showed any effect. We suggest that CD improvisation works as a
      training for change, inducing plasticity in flexible attention.

PMID- 21960972
TI  - Physiological environment induces quick response - slow exhaustion reactions.
AB  - In vivo environments are highly crowded and inhomogeneous, which may affect
      reaction processes in cells. In this study we examined the effects of
      intracellular crowding and an inhomogeneity on the behavior of in vivo reactions
      by calculating the spectral dimension (d(s)), which can be translated into the
      reaction rate function. We compared estimates of anomaly parameters obtained from
      fluorescence correlation spectroscopy (FCS) data with fractal dimensions derived
      from transmission electron microscopy (TEM) image analysis. FCS analysis
      indicated that the anomalous property was linked to physiological structure.
      Subsequent TEM analysis provided an in vivo illustration; soluble molecules
      likely percolate between intracellular clusters, which are constructed in a self
      organizing manner. We estimated a cytoplasmic spectral dimension d(s) to be 1.39
      +/- 0.084. This result suggests that in vivo reactions initially run faster than
      the same reactions in a homogeneous space; this conclusion is consistent with the
      anomalous character indicated by FCS analysis. We further showed that these
      results were compatible with our Monte-Carlo simulation in which the anomalous
      behavior of mobile molecules correlates with the intracellular environment,
      leading to description as a percolation cluster, as demonstrated using TEM
      analysis. We confirmed by the simulation that the above-mentioned in vivo like
      properties are different from those of homogeneously concentrated environments.
      Additionally, simulation results indicated that crowding level of an environment
      might affect diffusion rate of reactant. Such knowledge of the spatial
      information enables us to construct realistic models for in vivo diffusion and
      reaction systems.

PMID- 21960973
TI  - Letting the brain speak for itself.
AB  - Metaphors of Computation and Information tended to detract attention from the
      intrinsic modes of neural system functions, uncontaminated by the observer's role
      in collection, and interpretation of experimental data. Recognizing the self
      referential mode of function, and the propensity for self-organization to
      critical states requires a fundamentally new orientation, based on Complex System
      Dynamics as non-ergodic, non-stationary processes with inverse-power-law
      statistical distributions. Accordingly, local cooperative processes, intrinsic to
      neural structures, and of fractal nature, call for applying Fractional Calculus
      and models of Random Walks with long-term memory in Theoretical Neuroscience
      studies.

PMID- 21960974
TI  - The genetic component of the forced diving bradycardia response in mammals.
AB  - We contrasted the forced diving bradycardia between two genetically similar
      (inbred) rat strains (Fischer and Buffalo), compared to that of outbred rats
      (Wistar). The animals were habituated to forced diving for 4 weeks. Each animal
      was then tested during one 40 s dive on each of 3 days. The heart rate (f(H)) was
      measured before, during, and after each dive. Fischer and Buffalo exhibited
      marked difference in dive bradycardia (Fischer: 120.9 +/- 14.0 beats min(-1) vs.
      Buffalo: 92.8 +/- 12.8 beats min(-1), P < 0.05). Outbred rats showed an
      intermediate response (103.0 +/- 30.9 beats min(-1)) but their between-animal
      variability in mean dive f(H) and pre-diving resting f(H) were higher than the
      inbred strains (P < 0.05), which showed no difference (P > 0.05). The decreased
      variability in f(H) in inbred rats as compared with the outbred group indicates
      that reduced genetic variability minimizes variability of the diving bradycardia
      between individuals. Heritability within strains was assessed by the
      repeatability (R) index and was 0.93 +/- 0.05 for the outbred, 0.84 +/- 0.16 for
      Buffalo, and 0.80 +/- 0.12 for Fischer rats for f(H) during diving. Our results
      suggest that a portion of the mammalian diving bradycardia may be a heritable
      trait.

PMID- 21960975
TI  - Face Piercing (Body Art): Choosing Pleasure vs. Possible Pain and Posture
      Instability.
AB  - Piercings (body art, i.e., with jewelry) are more and more widespread. They can
      induce various complications such as infections, allergies, headaches, and
      various skin, cartilage, or dental problems, and represent a public health
      problem. We draw attention to possible side effects resulting from face piercing
      complications observed on four young adults such as eye misalignment, decreased
      postural control efficiency, and non-specific chronic back pain with associated
      comorbidity. We found that the origin was pierced jewelry on the face. Removing
      the jewelry restored eye alignment, improved postural control, and alleviated
      back pain in a lasting way. We suggest that pierced facial jewelry can disturb
      somaesthetic signals driven by the trigeminal nerve, and thus interfere with
      central integration processes, notably in the cerebellum and the vestibular
      nucleus involved in postural control and eye alignment. Facial piercings could
      induce sensory-motor conflict, exacerbate, or precipitate a pre-existing
      undetermined conflict, which leads pain and complaints. These findings are
      significant for health; further investigations would be of interest.

PMID- 21960976
TI  - If You Know Something, Say Something: Young Children's Problem with False
      Beliefs.
AB  - Whether young children understand that others may hold false beliefs is a hotly
      debated topic in psychology and neuroscience. Much evidence suggests that
      children do not pass this milestone in their understanding of other people until
      the age of 5 years. Other evidence suggests that they understand already in their
      second year. This study proposes a novel account of the logic of conversations
      about certain mental states. By modifying the discourse accordingly, children
      passed three false belief tasks at 3 years of age while they failed standard
      false belief tasks. The results support the view that even young children
      construe other people in adult-like psychological terms.

PMID- 21960977
TI  - Explicating Numerical Information: When and How Fingers Support (or Hinder)
      Number Comprehension and Handling.

PMID- 21960979
TI  - Error-related activity and correlates of grammatical plasticity.
AB  - Cognitive control involves not only the ability to manage competing task demands,
      but also the ability to adapt task performance during learning. This study
      investigated how violation-, response-, and feedback-related electrophysiological
      (EEG) activity changes over time during language learning. Twenty-two Dutch
      learners of German classified short prepositional phrases presented serially as
      text. The phrases were initially presented without feedback during a pre-test
      phase, and then with feedback in a training phase on two separate days spaced 1
      week apart. The stimuli included grammatically correct phrases, as well as
      grammatical violations of gender and declension. Without feedback, participants'
      classification was near chance and did not improve over trials. During training
      with feedback, behavioral classification improved and violation responses
      appeared to both types of violation in the form of a P600. Feedback-related
      negative and positive components were also present from the first day of
      training. The results show changes in the electrophysiological responses in
      concert with improving behavioral discrimination, suggesting that the activity is
      related to grammar learning.

PMID- 21960978
TI  - Active inference, attention, and motor preparation.
AB  - Perception is the foundation of cognition and is fundamental to our beliefs and
      consequent action planning. The Editorial (this issue) asks: "what mechanisms, if
      any, mediate between perceptual and cognitive processes?" It has recently been
      argued that attention might furnish such a mechanism. In this paper, we pursue
      the idea that action planning (motor preparation) is an attentional phenomenon
      directed toward kinesthetic signals. This rests on a view of motor control as
      active inference, where predictions of proprioceptive signals are fulfilled by
      peripheral motor reflexes. If valid, active inference suggests that attention
      should not be limited to the optimal biasing of perceptual signals in the
      exteroceptive (e.g., visual) domain but should also bias proprioceptive signals
      during movement. Here, we investigate this idea using a classical attention
      (Posner) paradigm cast in a motor setting. Specially, we looked for decreases in
      reaction times when movements were preceded by valid relative to invalid cues.
      Furthermore, we addressed the hierarchical level at which putative attentional
      effects were expressed by independently cueing the nature of the movement and the
      hand used to execute it. We found a significant interaction between the validity
      of movement and effector cues on reaction times. This suggests that attentional
      bias might be mediated at a low level in the motor hierarchy, in an intrinsic
      frame of reference. This finding is consistent with attentional enabling of top
      down predictions of proprioceptive input and may rely upon the same synaptic
      mechanisms that mediate directed spatial attention in the visual system.

PMID- 21960980
TI  - Language and the newborn brain: does prenatal language experience shape the
      neonate neural response to speech?
AB  - Previous research has shown that by the time of birth, the neonate brain responds
      specially to the native language when compared to acoustically similar non
      language stimuli. In the current study, we use near-infrared spectroscopy to ask
      how prenatal language experience might shape the brain response to language in
      newborn infants. To do so, we examine the neural response of neonates when
      listening to familiar versus unfamiliar language, as well as to non language
      stimuli. Twenty monolingual English-exposed neonates aged 0-3 days were tested.
      Each infant heard low-pass filtered sentences of forward English (familiar
      language), forward Tagalog (unfamiliar language), and backward English and
      Tagalog (non-language). During exposure, neural activation was measured across 12
      channels on each hemisphere. Our results indicate a bilateral effect of language
      familiarity on neonates' brain response to language. Differential brain
      activation was seen when neonates listened to forward Tagalog (unfamiliar
      language) as compared to other types of language stimuli. We interpret these
      results as evidence that the prenatal experience with the native language gained
      in utero influences how the newborn brain responds to language across brain
      regions sensitive to speech processing.

PMID- 21960981
TI  - Statistical learning of two artificial languages presented successively: how
      conscious?
AB  - Statistical learning is assumed to occur automatically and implicitly, but little
      is known about the extent to which the representations acquired over training are
      available to conscious awareness. In this study, we focus on whether the
      knowledge acquired in a statistical learning situation is available to conscious
      control. Participants were first exposed to an artificial language presented
      auditorily. Immediately thereafter, they were exposed to a second artificial
      language. Both languages were composed of the same corpus of syllables and
      differed only in the transitional probabilities. We first determined that both
      languages were equally learnable (Experiment 1) and that participants could learn
      the two languages and differentiate between them (Experiment 2). Then, in
      Experiment 3, we used an adaptation of the Process-Dissociation Procedure
      (Jacoby, 1991) to explore whether participants could consciously manipulate the
      acquired knowledge. Results suggest that statistical information can be used to
      parse and differentiate between two different artificial languages, and that the
      resulting representations are available to conscious control.

PMID- 21960982
TI  - Causal asymmetry across cultures: assigning causal roles in symmetric physical
      settings.
AB  - Causal cognition in the physical domain has been treated for a long time as if it
      were (1) objective and (2) independent of culture. Despite some evidence to the
      contrary, however, these implicit assumptions have been rarely ever explored
      systematically. While the pervasive tendency of people to consider one of two
      equally important entities as more important for bringing about an effect (as
      reported by White, 2006) meanwhile provides one type of counter-evidence for the
      first assumption, respective findings remained mute to the second. In order to
      scrutinize how robust such tendencies are across cultures - and, if not, on which
      aspects of culture they may depend - we asked German and Tongan participants to
      assign prime causality in nine symmetric settings. For most settings, strong
      asymmetries in both cultures were found, but not always in the same direction,
      depending on the task content and by virtue of the multifaceted character of
      "culture." This indicates that causal asymmetries, while indeed being a robust
      phenomenon across cultures, are also modulated by task-specific properties (such
      as figure-ground relations), and are subject to cultural influences.

PMID- 21960983
TI  - Re-appreciating the why of cognition: 35 years after marr and poggio.
AB  - Marr and Poggio's levels of description are one of the most well-known
      theoretical constructs of twentieth century cognitive science. It entails that
      behavior can and should be considered at three different levels: computation,
      algorithm, and implementation. In this contribution focus is on the computational
      level of description, the level that describes the "why" of cognition. I argue
      that the computational level should be taken as a starting point in devising
      experiments in cognitive (neuro)science. Instead, the starting point in empirical
      practice often is a focus on the stimulus or on some capacity of the cognitive
      system. The "why" of cognition tends to be ignored when designing research, and
      is not considered in subsequent inference from experimental results. The overall
      aim of this manuscript is to show how re-appreciation of the computational level
      of description as a starting point for experiments can lead to more informative
      experimentation.

PMID- 21960984
TI  - Physics of IED Blast Shock Tube Simulations for mTBI Research.
AB  - Shock tube experiments and simulations are conducted with a spherical gelatin
      filled skull-brain surrogate, in order to study the mechanisms leading to blast
      induced mild traumatic brain injury. A shock tube including sensor system is
      optimized to simulate realistic improvised explosive device blast profiles
      obtained from full scale field tests. The response of the skull-brain surrogate
      is monitored using pressure and strain measurements. Fluid-structure interaction
      is modeled using a combination of computational fluid dynamics (CFD) simulations
      for the air blast, and a finite element model for the structural response. The
      results help to understand the physics of wave propagation, from air blast into
      the skull-brain. The presence of openings on the skull and its orientation does
      have a strong effect on the internal pressure. A parameter study reveals that
      when there is an opening in the skull, the skull gives little protection and the
      internal pressure is fairly independent on the skull stiffness; the gelatin shear
      stiffness has little effect on the internal pressure. Simulations show that the
      presence of pressure sensors in the gelatin hardly disturbs the pressure field.

PMID- 21960985
TI  - Clinical characterization of symptomatic microangiopathic brain lesions.
AB  - BACKGROUND: Microangiopathic brain lesions can be separated in diffuse lesions -
      leukoaraiosis - and focal lesions - lacunes. Leukoaraiosis and lacunes are caused
      by common cerebrovascular risk factors, but whether they represent a common
      entity is not sufficiently investigated. The present study aimed to determine the
      clinical profiles associated with the extent of leukoaraiosis and lacunes.
      METHODS: Sixty-four consecutive patients with acute microangiopathic stroke were
      studied. Leukoaraiosis and lacunes were stratified according to their MRI-based
      extent. Standardized clinical assessment included clinical syndromes,
      cerebrovascular risk factors, cognitive performance, retinal imaging,
      ultrasonography, blood, and urine parameters. RESULTS: Different clinical
      profiles for leukoaraiosis and lacunes were found. Regarding leukoaraiosis, the
      cognitive scores (SISCO, mini mental score examination, mental examination) and
      the presence of hyperlipidemia decreased as the severity of leukoaraiosis
      increased. Univariate and multivariate analysis revealed that these cognitive
      score values as well as the presence of hyperlipidemia correlated significantly
      with no or only mild leukoaraiosis. Regarding lacunes, the percentage of
      migraine, previous stroke events, hydrocephalus, left ventricular hypertrophy,
      and a higher National Institutes of Health Stroke Scale increased as the number
      of lacunar lesions increased. Statistical analysis revealed that these parameters
      correlated not significantly with the number of lacunes. CONCLUSIONS: The
      findings suggests that leukoaraiosis and lacunes are different microangiopathic
      entities potentially requiering different treatment concepts.

PMID- 21960986
TI  - Sulfur metabolisms in epsilon- and gamma-proteobacteria in deep-sea hydrothermal
      fields.
AB  - In deep-sea hydrothermal systems, super hot and reduced vent fluids from the
      subseafloor blend with cold and oxidized seawater. Very unique and dense
      ecosystems are formed within these environments. Many molecular ecological
      studies showed that chemoautotrophic epsilon- and gamma-Proteobacteria are
      predominant primary producers in both free-living and symbiotic microbial
      communities in global deep-sea hydrothermal fields. Inorganic sulfur compounds
      are important substrates for the energy conservative metabolic pathways in these
      microorganisms. Recent genomic and metagenomic analyses and biochemical studies
      have contributed to the understanding of potential sulfur metabolic pathways for
      these chemoautotrophs. Epsilon-Proteobacteria use sulfur compounds for both
      electron-donors and -acceptors. On the other hand, gamma-Proteobacteria utilize
      two different sulfur-oxidizing pathways. It is hypothesized that differences
      between the metabolic pathways used by these two predominant proteobacterial
      phyla are associated with different ecophysiological strategies; extending the
      energetically feasible habitats with versatile energy metabolisms in the epsilon
      Proteobacteria and optimizing energy production rate and yield for relatively
      narrow habitable zones in the gamma-Proteobacteria.

PMID- 21960987
TI  - Cryptococcus neoformans modulates extracellular killing by neutrophils.
AB  - We recently established a key role for host sphingomyelin synthase (SMS) in
      regulating the killing activity of neutrophils against Cryptococcus neoformans.
      In this paper, we studied the effect of C. neoformans on the killing activity of
      neutrophils and whether SMS would still be a player against C. neoformans in
      immunocompromised mice lacking T and natural killer (NK) cells (Tgepsilon26
      mice). To this end, we analyzed whether C. neoformans would have any effect on
      neutrophil survival and killing in vitro and in vivo. We show that unlike Candida
      albicans, neither the presence nor the capsule size of C. neoformans cells have
      any effect on neutrophil viability. Interestingly, melanized C. neoformans cells
      totally abrogated the killing activity of neutrophils. We monitored how exposure
      of neutrophils to C. neoformans cells would interfere with any further killing
      activity of the conditioned medium and found that pre-incubation with live but
      not "heat-killed" fungal cells significantly inhibits further killing activity of
      the medium. We then studied whether activation of SMS at the site of C.
      neoformans infection is dependent on T and NK cells. Using matrix-assisted laser
      desorption-ionization tissue imaging in infected lung we found that similar to
      previous observations in the isogenic wild-type CBA/J mice, SM 16:0 levels are
      significantly elevated at the site of infection in mice lacking T and NK cells,
      but only at early time points. This study highlights that C. neoformans may
      negatively regulate the killing activity of neutrophils and that SMS activation
      in neutrophils appears to be partially independent of T and/or NK cells.

PMID- 21960988
TI  - Multiresolution analysis using wavelet, ridgelet, and curvelet transforms for
      medical image segmentation.
AB  - The experimental study presented in this paper is aimed at the development of an
      automatic image segmentation system for classifying region of interest (ROI) in
      medical images which are obtained from different medical scanners such as PET,
      CT, or MRI. Multiresolution analysis (MRA) using wavelet, ridgelet, and curvelet
      transforms has been used in the proposed segmentation system. It is particularly
      a challenging task to classify cancers in human organs in scanners output using
      shape or gray-level information; organs shape changes throw different slices in
      medical stack and the gray-level intensity overlap in soft tissues. Curvelet
      transform is a new extension of wavelet and ridgelet transforms which aims to
      deal with interesting phenomena occurring along curves. Curvelet transforms has
      been tested on medical data sets, and results are compared with those obtained
      from the other transforms. Tests indicate that using curvelet significantly
      improves the classification of abnormal tissues in the scans and reduce the
      surrounding noise.

PMID- 21960989
TI  - Patient Specific Dosimetry Phantoms Using Multichannel LDDMM of the Whole Body.
AB  - This paper describes an automated procedure for creating detailed patient
      specific pediatric dosimetry phantoms from a small set of segmented organs in a
      child's CT scan. The algorithm involves full body mappings from adult template to
      pediatric images using multichannel large deformation diffeomorphic metric
      mapping (MC-LDDMM). The parallel implementation and performance of MC-LDDMM for
      this application is studied here for a sample of 4 pediatric patients, and from 1
      to 24 processors. 93.84% of computation time is parallelized, and the efficiency
      of parallelization remains high until more than 8 processors are used. The
      performance of the algorithm was validated on a set of 24 male and 18 female
      pediatric patients. It was found to be accurate typically to within 1-2 voxels (2
      4 mm) and robust across this large and variable data set.

PMID- 21960990
TI  - High glucose increases metallothionein expression in renal proximal tubular
      epithelial cells.
AB  - Metallothionein (MT) is an intracellular metal-binding, cysteine-rich protein,
      and is a potent antioxidant that protects cells and tissues from oxidative
      stress. Although the major isoforms MT-1 and -2 (MT-1/-2) are highly inducible in
      many tissues, the distribution and role of MT-1/-2 in diabetic nephropathy are
      poorly understood. In this study, diabetes was induced in adult male rats by
      streptozotocin, and renal tissues were stained with antibodies for MT-1/-2. MT-1/
      2 expression was also evaluated in mProx24 cells, a mouse renal proximal tubular
      epithelial cell line, stimulated with high glucose medium and pretreated with the
      antioxidant vitamin E. MT-1/-2 expression was gradually and dramatically
      increased, mainly in the proximal tubular epithelial cells and to a lesser extent
      in the podocytes in diabetic rats, but was hardly observed in control rats. MT-1/
      2 expression was also increased by high glucose stimulation in mProx24 cells.
      Because the induction of MT was suppressed by pretreatment with vitamin E, the
      expression of MT-1/-2 is induced, at least in part, by high glucose-induced
      oxidative stress. These observations suggest that MT-1/-2 is induced in renal
      proximal tubular epithelial cells as an antioxidant to protect the kidney from
      oxidative stress, and may offer a novel therapeutic target against diabetic
      nephropathy.

PMID- 21960991
TI  - Gestational diabetes mellitus and risk of childhood overweight and obesity in
      offspring: a systematic review.
AB  - We systematically reviewed research examining the association between gestational
      diabetes (GDM) and childhood overweight and obesity. We identified studies from
      three sources: (1) a PubMed search of articles published between January 1990
      January 2011, (2) reference lists of publications from the PubMed search, and (3)
      reference lists of review articles. We included studies that examined GDM
      separately from pregestational diabetes and childhood overweight or obesity
      defined as BMI > 85th or 95th percentile. A total of 12 studies were included in
      the systematic review. Crude odds ratios for the relationship between GDM and
      childhood overweight or obesity ranged from 0.7 to 6.3; in 8 studies, the
      associations were not statistically significant. In only 3 studies were results
      adjusted for any confounders; in the 2 that adjusted for prepregnancy obesity,
      the GDM and childhood overweight or obesity associations were attenuated and not
      statistically significant after adjustment. This paper demonstrates inconsistent
      evidence of an association between GDM and offspring overweight and obesity due
      to the methodological limitations of existing studies. Recommendations for future
      research are presented, which address methodological challenges.

PMID- 21960993
TI  - Predictors of impaired glucose regulation in patients with non-alcoholic fatty
      liver disease.
AB  - INTRODUCTION. Many patients with non-alcoholic fatty liver disease (NAFLD) have
      impaired glucose regulation or type 2 diabetes mellitus (DM). We investigated
      characteristics of NAFLD patients associated with hyperglycemia. METHODS. During
      a 2-hour oral glucose tolerance test (OGTT), serum glucose and insulin were
      measured in 152 NAFLD patients. RESULTS. 48.7% of NAFLD patients had
      hyperglycemia. Age (odds ratio (OR) = 1.08, 95% confidence interval (CI): 1.03
      1.13), body mass index (BMI) (OR = 1.12, 95% CI: 1.01-1.25), and lower high
      density lipoprotein cholesterol (HDL-C) (OR = 0.95, 95% CI: 0.92-0.98) proved to
      be independent predictors of hyperglycemia. After OGTT, 30 min insulin was lower
      in hyperglycemic patients (74.2 +/- 49.7 versus 94.5 +/- 53.9 MUIU/mL, P = 0.02),
      while 90 min insulin (170.1 +/- 84.6 versus 122.9 +/- 97.7 MUU/mL, P = 0.01) and
      120 min insulin (164.0 +/- 101.2 versus 85.3 +/- 61.9 MUIU/mL, P < 0.01) were
      higher. CONCLUSIONS. NAFLD patients with higher BMI, lower HDL-C, or older age
      were more likely to have impaired glucose metabolism. An OGTT could be of value
      for early diagnosis of DM among this population.

PMID- 21960992
TI  - Low levels of serum paraoxonase activities are characteristic of metabolic
      syndrome and may influence the metabolic-syndrome-related risk of coronary artery
      disease.
AB  - Low concentrations of plasma high-density lipoprotein (HDLs) are characteristic
      in metabolic syndrome (MS). The antioxidant ability of HDLs is, at least in part,
      attributable to pleiotropic serum paraoxonase (PON1). Different PON1 activities
      have been assessed in 293 subjects with (n = 88) or without MS (n = 205) and with
      (n = 195) or without (n = 98) angiographically proven coronary artery disease
      (CAD). MS subjects had low PON1 activities, with a progressively decreasing trend
      by increasing the number of MS abnormalities. The activity versus 7-O-diethyl
      phosphoryl,3-cyano,4-methyl,7-hydroxycoumarin (DEPCyMC), which is considered a
      surrogate marker of PON1 concentration, showed the most significant association
      with MS, independently of both HDL and apolipoprotein A-I levels. Subjects with
      MS and low DEPCyMCase activity had the highest CAD risk (OR 4.34 with 95% CI 1.44
      13.10), while no significant increase of risk was found among those with MS but
      high DEPCyMCase activity (OR 1.45 with 95% CI 0.47-4.46). Our results suggest
      that low PON1 concentrations are typical in MS and may modulate the MS-related
      risk of CAD.

PMID- 21960994
TI  - Short-chain fatty acid propionate alleviates Akt2 knockout-induced myocardial
      contractile dysfunction.
AB  - BACKGROUND AND AIMS. Dysregulation of Akt has been implicated in diseases such as
      cancer and diabetes, although little is known about the role of Akt deficiency on
      cardiomyocyte contractile function. This study was designed to examine the effect
      of Akt2 knockout-induced cardiomyocyte contractile response and the effect of
      dietary supplementation of short-chain fatty acid propionate on Akt2 knockout
      induced cardiac dysfunction, if any. METHODS AND RESULTS. Adult male wild-type
      (WT) and Akt2 knockout mice were treated with propionate (0.3 g/kg, p.o.) or
      vehicle for 7 days. Oral glucose tolerance test (OGTT) was performed.
      Cardiomyocyte contractile function and mitochondrial membrane potential were
      assessed. Expression of insulin-signaling molecules Akt, PTEN, GSK3beta, and eNOS
      receptors for short-chain fatty acids GPR41, and GPR43 as well as protein
      phosphatase PP2AA, PP2AB, PP2C were evaluated using Western blot analysis. Our
      results revealed that Akt2 knockout led to overt glucose intolerance, compromised
      cardiomyocyte contractile function (reduced peak shortening and maximal velocity
      of shortening/relengthening as well as prolonged relengthening), loss of
      mitochondrial membrane potential, decreased GPR41 and elevated GPR43 expression,
      all of which, with the exception of glucose intolerance and elevated GPR43 level,
      were significantly attenuated by propionate. Neither Akt2 knockout nor propionate
      affected the expression of protein phosphatases, eNOS, pan, and phosphorylated
      PTEN and GSK3beta. CONCLUSIONS. Taken together, these data depicted that Akt2
      knockout may elicit cardiomyocyte contractile and mitochondrial defects and a
      beneficial role of propionate or short-chain fatty acids against Akt2 deficiency
      induced cardiac anomalies.

PMID- 21960995
TI  - Common variants of homocysteine metabolism pathway genes and risk of type 2
      diabetes and related traits in Indians.
AB  - Hyperhomocysteinemia, a risk factor for cardiovascular disorder, obesity, and
      type 2 diabetes, is prevalent among Indians who are at high risk of these
      metabolic disorders. We evaluated association of common variants of genes
      involved in homocysteine metabolism or its levels with type 2 diabetes, obesity,
      and related traits in North Indians. We genotyped 90 variants in initial phase
      (2.115 subjects) and replicated top signals in an independent sample set (2.085
      subjects). The variant MTHFR-rs1801133 was the top signal for association with
      type 2 diabetes (OR = 0.78 (95%  CI = 0.67-0.92), P = 0.003) and was also
      associated with 2 h postload plasma glucose (P = 0.04), high-density lipoprotein
      cholesterol (P = 0.004), and total cholesterol (P = 0.01) in control subjects.
      These associations were neither replicated nor significant after meta-analysis.
      Studies involving a larger study population and different ethnic groups are
      required before ruling out the role of these important candidate genes in type 2
      diabetes, obesity, and related traits.

PMID- 21960996
TI  - On the use of EEG or MEG brain imaging tools in neuromarketing research.
AB  - Here we present an overview of some published papers of interest for the
      marketing research employing electroencephalogram (EEG) and magnetoencephalogram
      (MEG) methods. The interest for these methodologies relies in their high-temporal
      resolution as opposed to the investigation of such problem with the functional
      Magnetic Resonance Imaging (fMRI) methodology, also largely used in the marketing
      research. In addition, EEG and MEG technologies have greatly improved their
      spatial resolution in the last decades with the introduction of advanced signal
      processing methodologies. By presenting data gathered through MEG and high
      resolution EEG we will show which kind of information it is possible to gather
      with these methodologies while the persons are watching marketing relevant
      stimuli. Such information will be related to the memorization and pleasantness
      related to such stimuli. We noted that temporal and frequency patterns of brain
      signals are able to provide possible descriptors conveying information about the
      cognitive and emotional processes in subjects observing commercial
      advertisements. These information could be unobtainable through common tools used
      in standard marketing research. We also show an example of how an EEG methodology
      could be used to analyze cultural differences between fruition of video
      commercials of carbonated beverages in Western and Eastern countries.

PMID- 21960998
TI  - Fecal incontinence: prevalence, severity, and quality of life data from an
      outpatient gastroenterology practice.
AB  - Background. The prevalence of fecal incontinence varies tremendously as a result
      of inadequate data collection methods. Few office-based studies have assessed the
      prevalence of fecal incontinence and none have looked at modifiable risk factors
      or effect on quality of life. Design, Settings, Patients, and Main Outcome
      Measures. Five hundred patients who visited our inner city, university-based
      gastroenterology practice, were asked about symptoms of fecal incontinence. We
      also retrospectively reviewed 500 charts to identify the frequency of patient
      physician reporting of fecal incontinence. Results. Of the 500 patients that were
      directly questioned, 58 (12%, 43 women, 15 men) admitted to fecal incontinence
      compared to 12 (2.4%) in the retrospective arm. Patients with fecal incontinence
      and loose/watery stool reported the lowest quality of life scores. While the
      average severity score was similar between men and women, women had a
      significantly lower average quality of life score (3.04 versus 2.51; P < 0.03).
      Conclusions. The identification of fecal incontinence increases when patients are
      directly questioned. Identifying and treating patients with loose stool is a
      potential strategy to improve quality of life in this patient population. In men
      and women with similar severity of fecal incontinence, women have a significantly
      lower quality of life.

PMID- 21960999
TI  - Hemodynamic monitoring today.

PMID- 21960997
TI  - The potential interplay of adipokines with toll-like receptors in the development
      of hepatocellular carcinoma.
AB  - Toll-like receptors (TLRs) are not only crucial to the initiation of the immune
      system, but also play a key role in several human inflammatory diseases.
      Hepatocellular carcinoma (HCC) is among those human cancers, which arise from
      sites of chronic inflammation. Therefore, a number of studies have explored the
      potential contribution of TLRs to HCC occurrence, which is initiated by exposure
      to chronic hepatic inflammation of different etiologies (including ethanol, and
      chronic B and C viral infections). Recent epidemiological data have shown the
      association of obesity and HCC development. Given the fact that adipose tissues
      can produce a variety of inflammation-related adipokines, obesity has been
      characterized as a state of chronic inflammation. Adipokines are therefore
      considered as important mediators linking inflammation to several metabolic
      diseases, including cancers. More recently, many experts have also shown the
      bridging role of TLRs between inflammation and metabolism. Hopefully, to retrieve
      the potential interaction between TLRs and adipokines in carcinogenesis of HCC
      will shed a new light on the therapeutic alternative for HCC. In this paper, the
      authors first review the respective roles of TLRs and adipokines, discuss their
      mutual interaction in chronic inflammation, and finally anticipate further
      investigations of this interaction in HCC development.

PMID- 21961000
TI  - Anaesthesia Management of Caesarean Section in Two Patients with Eisenmenger's
      Syndrome.
AB  - Recently two parturients with Eisenmenger's syndrome underwent caesarean section
      at our hospital. They were managed by a multidisciplinary team during their
      perioperative period. The caesarean sections were uneventfully performed, one
      under general anaesthesia and one with epidural anaesthesia, with delivery of two
      newborns with satisfactory Apgar scores. One patient died in the post-partum
      period, and the other did well. We discuss the anaesthetic considerations in
      managing these high-risk patients.

PMID- 21961002
TI  - Comparison of depth of anesthesia in different parts of maxilla when only buccal
      anesthesia was done for maxillary teeth extraction.
AB  - Objective. Recently, some authors reported that maxillary teeth could be
      extracted without using palatal anesthesia, but they did not clearly specify the
      extracted teeth. This is important, because apparently the local anesthetic
      solution infiltrates the maxilla and achieves a sufficient anesthesia in the
      palatal side. Thus, thickness of the bone may affect the depth of anesthesia. The
      aim of this study was to compare the depth of anesthesia in different parts of
      the maxilla when only a buccal infiltration anesthesia was done. Patients and
      Method. The maxilla was divided into anterior, premolar, and molar regions. In
      each region, 15 teeth were extracted with a single buccal infiltration. The
      patient marked the pain level on a numerical rating scale. Results. Anesthesia
      depth was sufficient and was not significantly different (P > 0.05) among three
      maxillary regions. Conclusion. Except for surgical interventions, all maxillary
      teeth can be extracted using only a buccal infiltration anesthesia.

PMID- 21961001
TI  - Utility of vascular endothelial growth factor inhibitors in the treatment of
      ovarian cancer: from concept to application.
AB  - Despite recent advances in the management of ovarian cancer, it remains the most
      lethal gynecologic malignancy. Vascular endothelial growth factor (VEGF) has been
      shown to play a pivotal role in the progression of ovarian cancer leading to the
      eventual development of malignant ascites. On this basis, agents rendering VEGF
      ineffective by neutralizing VEGF (bevacizumab), blocking its receptors
      (aflibercept), or interfering with the postreceptor signaling pathways
      (sunitinib) provide us with the rational treatment options. These agents are
      generally used in combination with the standard chemotherapeutic drugs. Here, we
      discuss the basis of and the logic behind the use of these agents in the
      treatment of epithelial ovarian cancer, as well as their evaluation in different
      preclinical and clinical studies.

PMID- 21961003
TI  - Periosteum: a highly underrated tool in dentistry.
AB  - The ultimate goal of any dental treatment is the regeneration of lost tissues and
      alveolar bone. Under the appropriate culture conditions, periosteal cells secrete
      extracellular matrix and form a membranous structure. The periosteum can be
      easily harvested from the patient's own oral cavity, where the resulting donor
      site wound is invisible. Owing to the above reasons, the periosteum offers a rich
      cell source for bone tissue engineering; hence, the regenerative potential of
      periosteum is immense. Although the use of periosteum as a regenerative tool has
      been extensive in general medical field, the regenerative potential of periosteum
      is highly underestimated in dentistry; therefore, the present paper reviews the
      current literature related to the regenerative potential of periosteum and gives
      an insight to the future use of periosteum in dentistry.

PMID- 21961004
TI  - Bacterial cellulose-hydroxyapatite nanocomposites for bone regeneration.
AB  - The aim of this study was to develop and to evaluate the biological properties of
      bacterial cellulose-hydroxyapatite (BC-HA) nanocomposite membranes for bone
      regeneration. Nanocomposites were prepared from bacterial cellulose membranes
      sequentially incubated in solutions of CaCl(2) followed by Na(2)HPO(4). BC-HA
      membranes were evaluated in noncritical bone defects in rat tibiae at 1, 4, and
      16 weeks. Thermogravimetric analyses showed that the amount of the mineral phase
      was 40%-50% of the total weight. Spectroscopy, electronic microscopy/energy
      dispersive X-ray analyses, and X-ray diffraction showed formation of HA crystals
      on BC nanofibres. Low crystallinity HA crystals presented Ca/P a molar ratio of
      1.5 (calcium-deficient HA), similar to physiological bone. Fourier transformed
      infrared spectroscopy analysis showed bands assigned to phosphate and carbonate
      ions. In vivo tests showed no inflammatory reaction after 1 week. After 4 weeks,
      defects were observed to be completely filled in by new bone tissue. The BC-HA
      membranes were effective for bone regeneration.

PMID- 21961005
TI  - Rac1 and Stathmin but Not EB1 Are Required for Invasion of Breast Cancer Cells in
      Response to IGF-I.
AB  - Cell migration is considered necessary for the invasion that accompanies the
      directional formation of the cellular protrusions termed lamellipodia. In
      invasive breast cancer MDA-MB-231 cells, lamellipodia formation is preceded by
      translocation of the actin cytoskeletal regulatory protein WAVE2 to the leading
      edge. WAVE2 translocation and lamellipodia formation require many signaling
      molecules, including PI3K, Rac1, Pak1, IRSp53, stathmin, and EB1, but whether
      these molecules are necessary for invasion remains unclear. In noninvasive breast
      cancer MCF7 cells, no lamellipodia were induced by IGF-I, whereas in MDA-MB-231
      cells, Rac1, stathmin, and EB1 were overexpressed. Depletion of Rac1 or stathmin
      by small interfering RNA abrogated the IGF-I-induced invasion of MDA-MB-231
      cells; however, depletion of EB1 did not, indicating the necessity of Rac1 and
      stathmin but not EB1 for invasion. The signaling pathway leading to cell invasion
      may not be identical but shares some common molecules, leading to cell migration
      through lamellipodia formation.

PMID- 21961008
TI  - The Value of Hysterosalpingography following Medical Treatment with Methotrexate
      for Ectopic Pregnancy.
AB  - After an ectopic pregnancy (EP) fertility decreases, mostly due to tubal factor.
      Hysterosalpingography (HSG) is the most cost-effective tool for tubal patency
      assessment. Objective. To evaluate the usefulness of a HSG after a medical
      treatment for an EP, in order to counsel women on the most appropriate way to
      conceive future pregnancies. Methods. Between 1998 and 2008, 144 patients were
      submitted to medical treatment for an EP and performed HSG 3 months after the
      event. Results. 72.2% of normal HSG, 18.8% with unilateral obstruction, 6.3%
      tubal patency with defect, and 2.8% bilateral obstruction. Conclusion. Routine
      HSG following medical treatment for an EP does not seem necessary, as it does not
      change the initial management in 97.2% of the cases, but might be considered in
      selected risk cases, permitting timely referral of patients to in vitro
      fertilization.

PMID- 21961006
TI  - Communication in fungi.
AB  - We will discuss fungal communication in the context of fundamental biological
      functions including mating, growth, morphogenesis, and the regulation of fungal
      virulence determinants. We will address intraspecies but also interkingdom
      signaling by systematically discussing the sender of the message, the molecular
      message, and receiver. Analyzing communication shows the close coevolution of
      fungi with organisms present in their environment giving insights into
      multispecies communication. A better understanding of the molecular mechanisms
      underlying microbial communication will promote our understanding of the "fungal
      communicome."

PMID- 21961007
TI  - Reduced formation of oxidative stress biomarkers and migration of mononuclear
      phagocytes in the cochleae of chinchilla after antioxidant treatment in acute
      acoustic trauma.
AB  - Objective. Inhibition of inflammation and free radical formation in the cochlea
      may be involved in antioxidant treatment in acute acoustic trauma. Procedure.
      Chinchilla were exposed to 105 dB sound pressure level octave band noise for 6
      hours. One group of chinchilla was treated with antioxidants after noise
      exposure. Auditory brainstem responses, outer hair cell counts, and
      immunohistochemical analyses of biomarkers in the cochlea were conducted.
      Results. The antioxidant treatment significantly reduced hearing threshold
      shifts, outer hair cell loss, numbers of CD45(+) cells, as well as 4-hydroxy-2
      nonenal and nitrotyrosine formation in the cochlea. Conclusion. Antioxidant
      treatment may provide protection to sensory cells by inhibiting formation of
      reactive oxygen and nitrogen products and migration of mononuclear phagocytes in
      the cochlea. The present study provides further evidence of effectiveness of
      antioxidant treatment in reducing permanent hearing loss.

PMID- 21961009
TI  - Radiofrequency ablation for treatment of symptomatic uterine fibroids.
AB  - The use of thermal energy-based systems to treat uterine fibroids has resulted in
      a plethora of devices that are less invasive and potentially as effective in
      reducing symptoms as traditional options such as myomectomy. Most thermal
      ablation devices involve hyperthermia (heating of tissue), which entails the
      conversion of an external electromagnetic or ultrasound waves into intracellular
      mechanical energy, generating heat. What has emerged from two decades of peer
      reviewed research is the concept that hyperthermic fibroid ablation, regardless
      of the thermal energy source, can create large areas of necrosis within fibroids
      resulting in reductions in fibroid volume, associated symptoms and the need for
      reintervention. When a greater percentage of a fibroid's volume is ablated,
      symptomatic relief is more pronounced, quality of life increases, and it is more
      likely that such improvements will be durable. We review radiofrequency ablation
      (RFA), one modality of hyperthermic fibroid ablation.

PMID- 21961010
TI  - Treatment of pulmonary sequestrations by means of endovascular embolization:
      future or fashion?
AB  - Bronchopulmonary sequestration is a rare malformation of the lower respiratory
      tract. Several methods of treatment have been described since the first
      publication. We present two cases of female adult patients with bronchopulmonary
      sequestration. In the first patient an unsuccessful attempt to treat the
      bronchopulmonary sequestration by means of arterial embolization is described.
      She was subsequently treated by means of surgical resection, which was the
      primary treatment for the second patient. Although endovascular techniques are
      becoming promising, in our opinion surgical resection remains the unique
      treatment for bronchopulmonary sequestration.

PMID- 21961011
TI  - Dexmedetomidine use in the setting of cocaine-induced hypertensive emergency and
      aortic dissection: a novel indication.
AB  - Aortic dissection is a potentially fatal but rare disease characterized by an
      aortic intimal tear with blood passing into the media creating a false lumen and
      with resultant high mortality depending on the location of dissection if not
      aggressively treated. Cocaine users are known to have a higher incidence of
      aortic dissection. We report here aortic dissection in a patient with cocaine
      abuse which did not respond to traditional medication regimes used currently in
      this setting. Worth mentioning is the use of an alpha-2 receptor selective
      agonist named Dexmedetomidine as a treatment modality to control hypertension in
      this patient, which is approved only for sedation of intubated and mechanically
      ventilated patients in the intensive care settings and for sedation during
      invasive procedures. This paper illustrates the practical beneficial role of
      Dexmedetomidine in controling blood pressure in the settings of cocaine-induced
      sympathetic surge when other treatment modalities fail.

PMID- 21961012
TI  - Liposarcoma of the spermatic cord: a case report.
AB  - Liposarcomas are malignant tumors derived embryologically from mesodermal
      tissues. An unusual site of presentation is the spermatic cord, presenting as an
      inguinal or scrotal mass. We report a rare case of a liposarcoma of the spermatic
      cord, mimicking a testicular tumor. The patient was operated, and an
      orchidectomy, including the tumor, was performed. To our knowledge, there are
      about 185 similar cases reported in the literature.

PMID- 21961013
TI  - An incidentaloma: primitive neuroectodermal tumor of the thymus.
AB  - After presenting for a routine screening exam, and 57-year-old man was diagnosed
      with an incidentaloma-a primitive neuroectodermal tumor (PNET) of the thymus. A
      member of the Ewing sarcoma family of tumors, a PNET is typically regarded as a
      malignancy of childhood and adolescence, usually occurring in the central nervous
      system. In the case at hand, our patient had an extremely unusual presentation,
      given his age and tumor location. Initial presentation is the only predictor for
      long-term survival. Current treatment recommendations advocate complete surgical
      resection whenever possible, radiation therapy, and adjuvant versus neoadjuvant
      chemotherapy.

PMID- 21961014
TI  - One-stage combined thoracic ancient schwannomas total removal and coronary artery
      bypass.
AB  - Ancient schwannoma is a rare variant of neural tumors though rarely seen in the
      thorax. The combination with coronary artery diseases is also rare. Here we
      describe a 66 year-old male who had undergone one-stage combined surgery for
      thoracic ancient schwannomas removal and coronary artery disease. The masses
      were, respectively, 13 cm in the middle mediastinum and 5 cm in diameter
      originating from the intercostal nerve. The tumors were successfully removed
      using sternotomy, and then a coronary artery bypass grafting was performed. Here
      we discuss this rare tumor in relation to the relevant literature.

PMID- 21961015
TI  - A solitary fibrous tumor of the pleura revealed by hiccups.
AB  - Solitary fibrous tumors of the pleura are rare and benign primary localized
      tumors; they possess a malignant potential and thus should be excised. We report
      a case of a 43-year-old woman, who had suffered for 5 years from right
      basithoracic pain associated with progressive dyspnea and persistent hiccups
      during the last 6 months. We have not found any similar case in the literature.
      Further testing after excision by thoracotomy revealed a solitary fibrous pleural
      tumor. A brief discussion of the clinical presentation and incidence of these
      tumors is included.

PMID- 21961016
TI  - Human fetal liver: an in vitro model of erythropoiesis.
AB  - We previously described the large-scale production of RBCs from hematopoietic
      stem cells (HSCs) of diverse sources. Our present efforts are focused to produce
      RBCs thanks to an unlimited source of stem cells. Human embryonic stem (ES) cells
      or induced pluripotent stem cell (iPS) are the natural candidates. Even if the
      proof of RBCs production from these sources has been done, their amplification
      ability is to date not sufficient for a transfusion application. In this work,
      our protocol of RBC production was applied to HSC isolated from fetal liver (FL)
      as an intermediate source between embryonic and adult stem cells. We studied the
      erythroid potential of FL-derived CD34(+) cells. In this in vitro model,
      maturation that is enucleation reaches a lower level compared to adult sources as
      observed for embryonic or iP, but, interestingly, they (i) displayed a dramatic
      in vitro expansion (100-fold more when compared to CB CD34(+)) and (ii) 100%
      cloning efficiency in hematopoietic progenitor assays after 3 days of erythroid
      induction, as compared to 10-15% cloning efficiency for adult CD34(+) cells. This
      work supports the idea that FL remains a model of study and is not a candidate
      for ex vivo RBCS production for blood transfusion as a direct source of stem
      cells but could be helpful to understand and enhance proliferation abilities for
      primitive cells such as ES cells or iPS.

PMID- 21961017
TI  - Phenotypic definition of the progenitor cells with erythroid differentiation
      potential present in human adult blood.
AB  - In Human Erythroid Massive Amplification (HEMA) cultures, AB mononuclear cells
      (MNC) generate 1-log more erythroid cells (EBs) than the corresponding CD34(pos)
      cells, suggesting that MNC may also contain CD34(neg) HPC. To clarify the
      phenotype of AB HPC which generate EBs in these cultures, flow cytometric
      profiling for CD34/CD36 expression, followed by isolation and functional
      characterization (colony-forming-ability in semisolid-media and fold-increase in
      HEMA) were performed. Four populations with erythroid differentiation potential
      were identified: CD34(pos)CD36(neg) (0.1%); CD34(pos)CD36(pos) (barely detectable
      0.1%); CD34(neg)CD36(low) (2%) and CD34(neg)CD36(neg) (75%). In semisolid-media,
      CD34(pos)CD36(neg) cells generated BFU-E and CFU-GM (in a 1 : 1 ratio),
      CD34(neg)CD36(neg) cells mostly BFU-E (87%) and CD34(pos)CD36(pos) and
      CD34(neg)CD36(low) cells were not tested due to low numbers. Under HEMA
      conditions, CD34(pos)CD36(neg), CD34(pos)CD36(pos), CD34(neg)CD36(low) and
      CD34(neg)CD36(neg) cells generated EBs with fold-increases of ~9,000, 100, 60 and
      1, respectively, and maturation times (day with >10% CD36(high)CD235a(high)
      cells) of 10-7 days. Pyrenocytes were generated only by CD34(neg)/CD36(neg) cells
      by day 15. These results confirm that the majority of HPC in AB express CD34 but
      identify additional CD34(neg) populations with erythroid differentiation
      potential which, based on differences in fold-increase and maturation times, may
      represent a hierarchy of HPC present in AB.

PMID- 21961018
TI  - Application of the Filariasis CELISA Antifilarial IgG(4) Antibody Assay in
      Surveillance in Lymphatic Filariasis Elimination Programmes in the South Pacific.
AB  - Elimination of lymphatic filariasis (LF) in the Pacific Island Countries and
      Territories (PICT) has been defined as <0.1% circulating filarial antigen (CFA)
      prevalence in children born after the implementation of successful mass drug
      administrations (MDAs). This research assessed the feasibility of CFA and
      antibody testing in three countries; Tonga, Vanuatu, and Samoa. Transmission is
      interrupted in Vanuatu and Tonga as evidenced by no CFA positive children and a
      low antibody prevalence and titre. Transmission is ongoing in Samoa with
      microfilaraemic (Mf) and CFA positive children and a high antibody prevalence and
      titre. Furthermore, areas of transmission were identified with Mf positive
      adults, but no CFA positive children. These areas had a high antibody prevalence
      in children. In conclusion, CFA testing in children alone was not useful for
      identifying areas of residual endemicity in Samoa. Thus, it would be beneficial
      to include antibody serology in the PICT surveillance strategy.

PMID- 21961019
TI  - Prevention of congenital transmission of malaria in sub-saharan african
      countries: challenges and implications for health system strengthening.
AB  - Objectives. Review of burden of congenital transmission of malaria, challenges of
      preventive measures, and implications for health system strengthening in sub
      Saharan Africa. Methods. Literature from Pubmed (MEDLINE), Biomed central, Google
      Scholar, and Cochrane Database were reviewed. Results. The prevalence of
      congenital malaria in sub-Saharan Africa ranges from 0 to 23%. Diagnosis and
      existing preventive measures are constantly hindered by weak health systems and
      sociocultural issues. WHO strategic framework for prevention: intermittent
      preventive therapy (IPT), insecticide-treated nets (ITNs), and case management of
      malaria illness and anaemia remain highly promising; though, specific
      interventions are required to strengthen the health systems in order to improve
      the effectiveness of these measures. Conclusion. Congenital malaria remains a
      public health burden in sub-Saharan Africa. Overcoming the challenges of the
      preventive measures hinges on the ability of national governments and development
      partners in responding to the weak health systems.

PMID- 21961020
TI  - Maximum aerobic capacity of underground coal miners in India.
AB  - Miners fitness test was assessed in terms of determination of maximum aerobic
      capacity by an indirect method following a standard step test protocol before
      going down to mine by taking into consideration of heart rates (Telemetric
      recording) and oxygen consumption of the subjects (Oxylog-II) during exercise at
      different working rates. Maximal heart rate was derived as 220-age. Coal miners
      reported a maximum aerobic capacity within a range of 35-38.3 mL/kg/min. It also
      revealed that oldest miners (50-59 yrs) had a lowest maximal oxygen uptake (34.2
      +/- 3.38 mL/kg/min) compared to (42.4 +/- 2.03 mL/kg/min) compared to (42.4 +/-
      2.03 mL/kg/min) the youngest group (20-29 yrs). It was found to be negatively
      correlated with age (r = -0.55 and -0.33 for younger and older groups
      respectively) and directly associated with the body weight of the subjects (r =
      0.57 - 0.68, P <= 0.001). Carriers showed maximum cardio respiratory capacity
      compared to other miners. Indian miners VO(2 max) was found to be lower both
      compared to their abroad mining counterparts and various other non-mining
      occupational working groups in India.

PMID- 21961021
TI  - Phenotyping of P105-negative B cell subsets in patients with systemic lupus
      erythematosus.
AB  - This study aimed to investigate phenotype of RP105(-) B cell subsets in patients
      with systemic lupus erythematosus (SLE). Flow cytometry was used for phenotyping
      RP105-negaive B cell subsets. Based on CD19, RP105, and CD138 expression, RP105(
      ) B cells consist of at least 5 subsets of late B cells, including
      CD19(+)RP105(int), CD19(+) RP105(-), CD19(low) RP105(-) CD138(-), CD19(low)
      RP105(-)CD138(int), and CD19(low) RP105(-) CD138(++) B cells. Especially,
      CD19(+)RP105(int) and CD19(low) RP105(-)CD138(int) B cells are significantly
      larger than other RP105(-) B cell subsets in SLE. By comparison of RP105(-) B
      cell subsets between patients with SLE and normal subjects, these subsets were
      detectable even in normal subjects, but the percentages of RP105(-) B cell
      subsets were significantly larger in SLE. The phenotypic analysis of RP105(-) B
      cell subsets suggests dysregulation of later B cell subsets in SLE and may
      provide new insights into understanding regulation of B cells in human SLE.

PMID- 21961022
TI  - Lactococcus lactis NCC 2287 alleviates food allergic manifestations in sensitized
      mice by reducing IL-13 expression specifically in the ileum.
AB  - OBJECTIVE: Utilizing a food allergy murine model, we have investigated the
      intrinsic antiallergic potential of the Lactococcus lactis NCC 2287 strain.
      METHODS: BALB/c mice were sensitized at weekly intervals with ovalbumin (OVA)
      plus cholera toxin (CT) by the oral route for 7 weeks. In this model, an oral
      challenge with a high dose of OVA at the end of the sensitization period leads to
      clinical symptoms. Lactococcus lactis NCC 2287 was given to mice via the drinking
      water during sensitization (prevention phase) or after sensitization (management
      phase). RESULTS: Lactococcus lactis NCC 2287 administration to sensitized mice
      strikingly reduced allergic manifestations in the management phase upon
      challenge, when compared to control mice. No preventive effect was observed with
      the strain. Lactococcus lactis NCC 2287 significantly decreased relative
      expression levels of the Th-2 cytokine, IL-13, and associated chemokines CCL11
      (eotaxin-1) and CCL17 (TARC) in the ileum. No effect was observed in the jejunum.
      CONCLUSION/SIGNIFICANCE: These results taken together designate Lactococcus
      lactis NCC 2287 as a candidate probiotic strain appropriate in the management of
      allergic symptoms.

PMID- 21961024
TI  - Involvement of prohibitin upregulation in abrin-triggered apoptosis.
AB  - Abrin (ABR), a protein purified from the seeds of Abrus precatorius, induces
      apoptosis in various types of cancer cells. However, the detailed mechanism
      remains largely uncharacterized. By using a cDNA microarray platform, we
      determined that prohibitin (PHB), a tumor suppressor protein, is significantly
      upregulated in ABR-triggered apoptosis. ABR-induced upregulation of PHB is
      mediated by the stress-activated protein kinase/c-Jun NH2-terminal kinase
      (SAPK/JNK) pathway, as demonstrated by chemical inhibitors. In addition, ABR
      significantly induced the expression of Bax as well as the activation of caspase
      3 and poly(ADP-ribose) polymerase (PARP) in Jurkat T cells, whereas the reduction
      of PHB by specific RNA interference delayed ABR-triggered apoptosis through the
      proapoptotic genes examined. Moreover, our results also indicated that nuclear
      translocation of the PHB-p53 complex may play a role in the transcription of Bax.
      Collectively, our data show that PHB plays a role in ABR-induced apoptosis, which
      may be helpful for the development of diagnostic or therapeutic agents.

PMID- 21961023
TI  - Bioactive pigments from marine bacteria: applications and physiological roles.
AB  - Research into natural products from the marine environment, including
      microorganisms, has rapidly increased over the past two decades. Despite the
      enormous difficulty in isolating and harvesting marine bacteria, microbial
      metabolites are increasingly attractive to science because of their broad-ranging
      pharmacological activities, especially those with unique color pigments. This
      current review paper gives an overview of the pigmented natural compounds
      isolated from bacteria of marine origin, based on accumulated data in the
      literature. We review the biological activities of marine compounds, including
      recent advances in the study of pharmacological effects and other commercial
      applications, in addition to the biosynthesis and physiological roles of
      associated pigments. Chemical structures of the bioactive compounds discussed are
      also presented.

PMID- 21961025
TI  - Ethnobotany in Intermedical Spaces: The Case of the Fulni-o Indians (Northeastern
      Brazil).
AB  - We analyzed the Fulni-o medical system and introduced its intermedical character
      based on secondary data published in the literature. Then we focused on the
      medicinal plants known to the ethnic group, describing the most important
      species, their therapeutic uses and the body systems attributed to them. We based
      this analysis on the field experience of the authors in the project Studies for
      the Environmental and Cultural Sustainability of the Fulni-o Medical System:
      Office of Medicinal Plant Care. This traditional botanical knowledge was used to
      corroborate the hybrid nature of local practices for access to health. We show
      that intermedicality is a result not only of the meeting of the Fulni-o medical
      system with Biomedicine but also of its meeting with other traditional systems.
      Finally, we discuss how traditional botanical knowledge may be directly related
      to the ethnogenesis process led by the Fulni-o Indians in northeastern Brazil.

PMID- 21961026
TI  - Highlighting anatomical sub-structures in rat brain tissue using lipid imaging.
AB  - Cell membranes are made up of a mixture of glycerolipids, sphingolipids,
      gangliosides and cholesterol. Lipids play important roles in a cell's life.
      However many of their functions have still to be discovered. In the present work,
      we describe an efficient, easy and rapid methodology to accurately localize
      phosphatidylcholines and sphingomyelins from a single coronal rat brain section
      in the cerebrum area. Matrix assisted laser desorption/ionization (MALDI) mass
      spectrometry was used to profile and image lipids. The best resolved structure
      was 25-50 MUm in the hippocampus.

PMID- 21961027
TI  - Recombinant T cell receptor ligands improve outcome after experimental cerebral
      ischemia.
AB  - A key target for novel stroke therapy is the regulation of post-ischemic
      inflammatory mechanisms. Recent evidence emphasizes the role of T lymphocytes of
      differing subtypes in the evolution is ischemic brain damage. We have recently
      demonstrated the benefit of myelin antigen-specific immunodulatory agents known
      as recombinant T cell receptor ligands (RTLs) in a standard murine model of focal
      stroke. The aim of the current study was to extend this initial observation to
      RTL treatment in a therapeutically relevant timing after middle cerebral artery
      occlusion (MCAO) and verify functional benefit to complement histological outcome
      measures. We observed that the administration of mouse-specific RTL551 reduced
      infarct size and improved sensorimotor outcome when administered within a 3 h
      post-ischemic therapeutic window. RTL551 treatment reduced cortical, caudate
      putamen, and total infarct volume as compared to vehicle-treated mice. Using a
      standard behavioral testing repertoire, we observed that RTL551 reduced
      sensorimotor impairment 3 days after MCAO. Humanized RTL1000 (HLA-DR2 moiety
      linked to hMOG-35-55 peptide) also reduced infarct size in HLA-DR2 transgenic
      mice. These data indicate that this neuroantigen-specific immunomodulatory agent
      reduces damage when administered in a therapeutically relevant reperfusion
      timeframe. 

PMID- 21961028
TI  - Estrogen and P2 Purinergic Receptor Systems in Microglia: Therapeutic Targets for
      Neuroprotection.
AB  - Microglia, the primary resident immune cell population in the CNS, react to
      signals of injury or infection and produce inflammatory cytokines, chemokines,
      and reactive oxygen species, many of which can be neurotoxic in large quantities.
      Indeed microglial hyperactivation is thought to contribute to the pathology of
      many neurodegenerative disorders as well as ischemic and traumatic brain
      injuries, suggesting that agents with the capacity to target microglial
      activities may be beneficial for treating neuronal injury. In this review, we
      discuss two seemingly unrelated microglial receptor signaling systems that
      potently modulate many microglial properties; purinergic P2 and estrogen
      receptors. Purinergic receptors regulate key microglial functions, including
      their production of pro-inflammatory cytokines, neurotrophic factors, migration,
      phagocytosis and chemotaxis. Many of these same endpoints are also altered by
      estrogen receptor signaling in microglia. Here we summarize the current
      microglial research in both receptor areas, particularly as it relates to
      ischemic and traumatic CNS injuries. We provide evidence from our own laboratory
      of potential cross-talk between these receptor systems and discuss evidence
      indicating that both purinergic and estrogen receptors may represent useful
      therapeutic targets for the treatment of CNS disorders.

PMID- 21961029
TI  - The CPT1C 5'UTR contains a repressing upstream open reading frame that is
      regulated by cellular energy availability and AMPK.
AB  - BACKGROUND: Translational control is utilized as a means of regulating gene
      expression in many species. In most cases, posttranscriptional regulatory
      mechanisms play an important role in stress response pathways and can lead to
      dysfunctional physiology if blocked by mutations. Carnitine Palmitoyltransferase
      1 C (CPT1C), the brain-specific member of the CPT 1 family, has previously been
      shown to be involved in regulating metabolism in situations of energy surplus.
      PRINCIPAL FINDINGS: Sequence analysis of the CPT1C mRNA revealed that it contains
      an upstream open reading frame (uORF) in the 5' UTR of its mRNA. Using CPT1C 5'
      UTR/luciferase constructs, we investigated the role of the uORF in translational
      regulation. The results presented here show that translation from the CPT1C main
      open reading frame (mORF) is repressed by the presence of the uORF, that this
      repression is relieved in response to specific stress stimuli, namely glucose
      deprivation and palmitate-BSA treatment, and that AMPK inhibition can relieve
      this uORF-dependent repression. SIGNIFICANCE: The fact that the mORF regulation
      is relieved in response to a specific set of stress stimuli rather than general
      stress response, hints at an involvement of CPT1C in cellular energy-sensing
      pathways and provides further evidence for a role of CPT1C in hypothalamic
      regulation of energy homeostasis.

PMID- 21961030
TI  - Differential changes in QTc duration during in-hospital haloperidol use.
AB  - AIMS: To evaluate changes in QT duration during low-dose haloperidol use, and
      determine associations between clinical variables and potentially dangerous QT
      prolongation. METHODS: In a retrospective cohort study in a tertiary university
      teaching hospital in The Netherlands, all 1788 patients receiving haloperidol
      between 2005 and 2007 were studied; ninety-seven were suitable for final
      analysis. Rate-corrected QT duration (QTc) was measured before, during and after
      haloperidol use. Clinical variables before haloperidol use and at the time of
      each ECG recording were retrieved from hospital charts. Mixed model analysis was
      used to estimate changes in QT duration. Risk factors for potentially dangerous
      QT prolongation were estimated by logistic regression analysis. RESULTS: Patients
      with normal before-haloperidol QTc duration (male <=430 ms, female <=450 ms) had
      a significant increase in QTc duration of 23 ms during haloperidol use; twenty
      three percent of patients rose to abnormal levels (male >=450 ms, female >=470
      ms). In contrast, a significant decrease occurred in patients with borderline
      (male 430-450 ms, female 450-470 ms) or abnormal before-haloperidol QTc duration
      (15 ms and 46 ms, respectively); twenty-three percent of patients in the
      borderline group, and only 9% of patients in the abnormal group obtained abnormal
      levels. Potentially dangerous QTc prolongation was independently associated with
      surgery before haloperidol use (OR(adj) 34.9, p = 0.009) and before-haloperidol
      QTc duration (OR(adj) 0.94, p = 0.004). CONCLUSION: QTc duration during
      haloperidol use changes differentially, increasing in patients with normal before
      haloperidol QTc duration, but decreasing in patients with prolonged before
      haloperidol QTc duration. Shorter before-haloperidol QTc duration and surgery
      before haloperidol use predict potentially dangerous QTc prolongation.

PMID- 21961031
TI  - High refractive index silicone gels for simultaneous total internal reflection
      fluorescence and traction force microscopy of adherent cells.
AB  - Substrate rigidity profoundly impacts cellular behaviors such as migration, gene
      expression, and cell fate. Total Internal Reflection Fluorescence (TIRF)
      microscopy enables selective visualization of the dynamics of substrate
      adhesions, vesicle trafficking, and biochemical signaling at the cell-substrate
      interface. Here we apply high-refractive-index silicone gels to perform TIRF
      microscopy on substrates with a wide range of physiological elastic moduli and
      simultaneously measure traction forces exerted by cells on the substrate.

PMID- 21961032
TI  - Acute effects of nicotine amplify accumbal neural responses during nicotine
      taking behavior and nicotine-paired environmental cues.
AB  - Nicotine self-administration (SA) is maintained by several variables, including
      the reinforcing properties of nicotine-paired cues and the nicotine-induced
      amplification of those cue properties. The nucleus accumbens (NAc) is implicated
      in mediating the influence of these variables, though the underlying
      neurophysiological mechanisms are not yet understood. In the present study, Long
      Evans rats were trained to self-administer nicotine. During SA sessions each
      press of a lever was followed by an intravenous infusion of nicotine (30 ug/kg)
      paired with a combined light-tone cue. Extracellular recordings of single-neuron
      activity showed that 20% of neurons exhibited a phasic change in firing during
      the nicotine-directed operant, the light-tone cue, or both. The phasic change in
      firing for 98% of neurons was an increase. Sixty-two percent of NAc neurons
      additionally or alternatively showed a sustained decrease in average firing
      during the SA session relative to a presession baseline period. These session
      decreases in firing were significantly less prevalent in a group of neurons that
      were activated during either the operant or the cue than in a group of neurons
      that were nonresponsive during those events (referred to as task-activated and
      task-nonactivated neurons, respectively). Moreover, the session decrease in
      firing was dose-dependent for only the task-nonactivated neurons. The data of the
      present investigation provide supportive correlational evidence for two
      hypotheses: (1) excitatory neurophysiological mechanisms mediate the NAc role in
      cue-maintenance of nicotine SA, and (2) a differential nicotine-induced
      inhibition of task-activated and task-nonactivated neurons mediates the NAc role
      in nicotine-induced amplification of cue effects on nicotine SA.

PMID- 21961033
TI  - A Mycobacterium leprae Hsp65 mutant as a candidate for mitigating lupus
      aggravation in mice.
AB  - Hsp60 is an abundant and highly conserved family of intracellular molecules.
      Increased levels of this family of proteins have been observed in the
      extracellular compartment in chronic inflammation. Administration of M. leprae
      Hsp65 [WT] in [NZBxNZW]F(1) mice accelerates the Systemic Lupus Erythematosus
      [SLE] progression whereas the point mutated K(409)A Hsp65 protein delays the
      disease. Here, the biological effects of M. leprae Hsp65 Leader pep and K(409)A
      pep synthetic peptides, which cover residues 352-371, are presented. Peptides had
      immunomodulatory effects similar to that observed with their respective proteins
      on survival and the combined administration of K(409)A+Leader pep or K(409)A
      pep+WT showed that the mutant forms were able to inhibit the deleterious effect
      of WT on mortality, indicating the neutralizing potential of the mutant molecules
      in SLE progression. Molecular modeling showed that replacing Lysine by Alanine
      affects the electrostatic potential of the 352-371 region. The number of
      interactions observed for WT is much higher than for Hsp65 K(409)A and mouse
      Hsp60. The immunomodulatory effects of the point-mutated protein and peptide
      occurred regardless of the catalytic activity. These findings may be related to
      the lack of effect on survival when F(1) mice were inoculated with Hsp60 or
      K(409)A pep. Our findings indicate the use of point-mutated Hsp65 molecules, such
      as the K(409)A protein and its corresponding peptide, that may minimize or delay
      the onset of SLE, representing a new approach to the treatment of autoimmune
      diseases.

PMID- 21961034
TI  - Tauroursodeoxycholic acid (TUDCA) protects photoreceptors from cell death after
      experimental retinal detachment.
AB  - BACKGROUND: Detachment of photoreceptors from the underlying retinal pigment
      epithelium is seen in various retinal disorders such as retinal detachment and
      age-related macular degeneration and leads to loss of photoreceptors and vision.
      Pharmacologic inhibition of photoreceptor cell death may prevent this outcome.
      This study tests whether systemic administration of tauroursodeoxycholic acid
      (TUDCA) can protect photoreceptors from cell death after experimental retinal
      detachment in rodents. METHODOLOGY/PRINCIPAL FINDINGS: Retinal detachment was
      created in rats by subretinal injection of hyaluronic acid. The animals were
      treated daily with vehicle or TUDCA (500 mg/kg). TUNEL staining was used to
      evaluate cell death. Photoreceptor loss was evaluated by measuring the relative
      thickness of the outer nuclear layer (ONL). Macrophage recruitment, oxidative
      stress, cytokine levels, and caspase levels were also quantified. Three days
      after detachment, TUDCA decreased the number of TUNEL-positive cells compared to
      vehicle (651+/-68/mm(2) vs. 1314+/-68/mm(2), P = 0.001) and prevented the
      reduction of ONL thickness ratio (0.84+/-0.03 vs. 0.65+/-0.03, P = 0.002).
      Similar results were obtained after 5 days of retinal detachment. Macrophage
      recruitment and expression levels of TNF-a and MCP-1 after retinal detachment
      were not affected by TUDCA treatment, whereas increases in activity of caspases 3
      and 9 as well as carbonyl-protein adducts were almost completely inhibited by
      TUDCA treatment. CONCLUSIONS/SIGNIFICANCE: Systemic administration of TUDCA
      preserved photoreceptors after retinal detachment, and was associated with
      decreased oxidative stress and caspase activity. TUDCA may be used as a novel
      therapeutic agent for preventing vision loss in diseases that are characterized
      by photoreceptor detachment.

PMID- 21961035
TI  - Activity dependent protein degradation is critical for the formation and
      stability of fear memory in the amygdala.
AB  - Protein degradation through the ubiquitin-proteasome system [UPS] plays a
      critical role in some forms of synaptic plasticity. However, its role in memory
      formation in the amygdala, a site critical for the formation of fear memories,
      currently remains unknown. Here we provide the first evidence that protein
      degradation through the UPS is critically engaged at amygdala synapses during
      memory formation and retrieval. Fear conditioning results in NMDA-dependent
      increases in degradation-specific polyubiquitination in the amygdala, targeting
      proteins involved in translational control and synaptic structure and blocking
      the degradation of these proteins significantly impairs long-term memory.
      Furthermore, retrieval of fear memory results in a second wave of NMDA-dependent
      polyubiquitination that targets proteins involved in translational silencing and
      synaptic structure and is critical for memory updating following recall. These
      results indicate that UPS-mediated protein degradation is a major regulator of
      synaptic plasticity necessary for the formation and stability of long-term
      memories at amygdala synapses.

PMID- 21961036
TI  - Gibberellin A1 metabolism contributes to the control of photoperiod-mediated
      tuberization in potato.
AB  - Some potato species require a short-day (SD) photoperiod for tuberization, a
      process that is negatively affected by gibberellins (GAs). Here we report the
      isolation of StGA3ox2, a gene encoding a GA 3-oxidase, whose expression is
      increased in the aerial parts and is repressed in the stolons after transfer of
      photoperiod-dependent potato plants to SD conditions. Over-expression of StGA3ox2
      under control of constitutive or leaf-specific promoters results in taller plants
      which, in contrast to StGA20ox1 over-expressers previously reported, tuberize
      earlier under SD conditions than the controls. By contrast, StGA3ox2 tuber
      specific over-expression results in non-elongated plants with slightly delayed
      tuber induction. Together, our experiments support that StGA3ox2 expression and
      gibberellin metabolism significantly contribute to the tuberization time in
      strictly photoperiod-dependent potato plants.

PMID- 21961037
TI  - Complexity of bidirectional transcription and alternative splicing at human RCAN3
      locus.
AB  - Human RCAN3 (regulator of calcineurin 3) belongs to the human RCAN gene family.In
      this study we provide, with in silico and in vitro analyses, the first detailed
      description of the human multi-transcript RCAN3 locus. Its analysis revealed that
      it is composed of a multigene system that includes at least 21 RCAN3 alternative
      spliced isoforms (16 of them identified here for the first time) and a new RCAN3
      antisense gene (RCAN3AS). In particular, we cloned RCAN3-1,3,4,5 (lacking exon
      2), RCAN3-1a,2,3,4,5, RCAN3-1a,3,4,5, RCAN3-1b,2,3,4,5, RCAN3-1c,2,3,4,5, RCAN3
      1c,2,4,5 and RCAN3-1c,3,4,5, isoforms that present a different 5' untranslated
      region when compared to RCAN3. Moreover, in order to verify the possible 5'
      incompleteness of previously identified cDNA isoforms with the reference exon 1,
      ten more alternative isoforms were retrieved. Bioinformatic searches allowed us
      to identify RCAN3AS, which overlaps in part with exon 1a, on the opposite strand,
      for which four different RCAN3AS isoforms were cloned.In order to analyze the
      different expression patterns of RCAN3 alternative first exons and of RCAN3AS
      mRNA isoforms, RT-PCR was performed in 17 human tissues. Finally, analyses of
      RCAN3 and RCAN3AS genomic sequences were performed to identify possible promoter
      regions, to examine donor and acceptor splice sequences and to compare
      evolutionary conservation, in particular of alternative exon 1 or 1c--exon 2
      junctions in different species.The description of its number of transcripts, of
      their expression patterns and of their regulatory regions can be important to
      clarify the functions of RCAN3 gene in different pathways and cellular processes.

PMID- 21961038
TI  - Control of cell migration and inflammatory mediators production by CORM-2 in
      osteoarthritic synoviocytes.
AB  - BACKGROUND: Osteoarthritis (OA) is the most widespread degenerative joint
      disease. Inflamed synovial cells contribute to the release of inflammatory and
      catabolic mediators during OA leading to destruction of articular tissues. We
      have shown previously that CO-releasing molecules exert anti-inflammatory effects
      in animal models and OA chondrocytes. We have studied the ability of CORM-2 to
      modify the migration of human OA synoviocytes and the production of chemokines
      and other mediators sustaining inflammatory and catabolic processes in the OA
      joint. METHODOLOGY/PRINCIPAL FINDINGS: OA synoviocytes were stimulated with
      interleukin(IL)-1beta in the absence or presence of CORM-2. Migration assay was
      performed using transwell chambers. Gene expression was analyzed by quantitative
      PCR and protein expression by Western Blot and ELISA. CORM-2 reduced the
      proliferation and migration of OA synoviocytes, the expression of IL-8, CCL2,
      CCL20, matrix metalloproteinase(MMP)-1 and MMP-3, and the production of oxidative
      stress. We found that CORM-2 reduced the phosphorylation of extracellular signal
      regulated kinase1/2, c-Jun N-terminal kinase1/2 and to a lesser extent p38. Our
      results also showed that CORM-2 significantly decreased the activation of nuclear
      factor-kappaB and activator protein-1 regulating the transcription of chemokines
      and MMPs in OA synoviocytes. CONCLUSION/SIGNIFICANCE: A number of synoviocyte
      functions relevant in OA synovitis and articular degradation can be down
      regulated by CORM-2. These results support the interest of this class of agents
      for the development of novel therapeutic strategies in inflammatory and
      degenerative conditions.

PMID- 21961039
TI  - Bovine tuberculosis prevalence survey on cattle in the rural livestock system of
      Torodi (Niger).
AB  - BACKGROUND: Bovine tuberculosis (BTB) is a widespread zoonosis in developing
      countries but has received little attention in sub-Saharan Africa, especially in
      Niger. Recent investigations confirmed the high incidence of the disease in
      cattle slaughtered in an abattoir in Niamey. The fact that most of the animals in
      which M. bovis has been identified were from the rural area of Torodi implied the
      existence of a probable source of BTB in this region. This study aimed to
      determine the prevalence of BTB infection in cattle and to identify risk factors
      for infection in human and cattle populations in Torodi. METHODS AND PRINCIPAL
      FINDINGS: A survey was carried out at the level of households keeping livestock
      (n = 51). The questionnaire was related to the potential risk factors and the
      presence of clinical signs of TB both in animals and humans. Comparative
      Intradermal Tuberculin Test was conducted to determine the TB status in cattle (n
      = 393). The overall apparent individual animal prevalence of tuberculin reactors
      was 3.6% (CI: 95%, 1.9-5.9), whereas the individual true prevalence was estimated
      at 0.8% (CI: 95%, 0.0-5.0). Using a multivariate logistic regression analysis and
      a classification tree analysis, the only household level risk factor that
      significantly influenced the presence of BTB in cattle was the presence of
      animals coughing in the herd (OR = 4.7, 95% CI: 1.12-19.71, p-value = 0.034). The
      lack of the practice of quarantine was borderline significant (OR = 4.2, 95% CI:
      0.96-18.40, p-value = 0.056). CONCLUSION/SIGNIFICANCE: The study confirmed that
      BTB is endemic in cattle in Torodi and the risk of the transmission of the
      disease to humans is potentially high. For the control of the disease in
      livestock, slaughtering of infected animals and the compensation of the owners is
      needed. Collaboration between the veterinary and the medical sectors, in the
      diagnosis, monitoring, prevention and control of BTB is strongly encouraged.

PMID- 21961040
TI  - Multimodal functional network connectivity: an EEG-fMRI fusion in network space.
AB  - EEG and fMRI recordings measure the functional activity of multiple coherent
      networks distributed in the cerebral cortex. Identifying network interaction from
      the complementary neuroelectric and hemodynamic signals may help to explain the
      complex relationships between different brain regions. In this paper, multimodal
      functional network connectivity (mFNC) is proposed for the fusion of EEG and fMRI
      in network space. First, functional networks (FNs) are extracted using spatial
      independent component analysis (ICA) in each modality separately. Then the
      interactions among FNs in each modality are explored by Granger causality
      analysis (GCA). Finally, fMRI FNs are matched to EEG FNs in the spatial domain
      using network-based source imaging (NESOI). Investigations of both synthetic and
      real data demonstrate that mFNC has the potential to reveal the underlying neural
      networks of each modality separately and in their combination. With mFNC,
      comprehensive relationships among FNs might be unveiled for the deep exploration
      of neural activities and metabolic responses in a specific task or neurological
      state.

PMID- 21961041
TI  - Development of secondary woodland in oak wood pastures reduces the richness of
      rare epiphytic lichens.
AB  - Wooded pastures with ancient trees were formerly abundant throughout Europe, but
      during the last century, grazing has largely been abandoned often resulting in
      dense forests. Ancient trees constitute habitat for many declining and threatened
      species, but the effects of secondary woodland on the biodiversity associated
      with these trees are largely unknown. We tested for difference in species
      richness, occurrence, and abundance of a set of nationally and regionally red
      listed epiphytic lichens between ancient oaks located in secondary woodland and
      ancient oaks located in open conditions. We refined the test of the effect of
      secondary woodland by also including other explanatory variables. Species
      occurrence and abundance were modelled jointly using overdispersed zero-inflated
      Poisson models. The richness of the red-listed lichens on ancient oaks in
      secondary woodland was half of that compared with oaks growing in open
      conditions. The species-level analyses revealed that this was mainly the result
      of lower occupancy of two of the study species. The tree-level abundance of one
      species was also lower in secondary woodland. Potential explanations for this
      pattern are that the study lichens are adapted to desiccating conditions
      enhancing their population persistence by low competition or that open, windy
      conditions enhance their colonisation rate. This means that the development of
      secondary woodland is a threat to red-listed epiphytic lichens. We therefore
      suggest that woody vegetation is cleared and grazing resumed in abandoned oak
      pastures. Importantly, this will also benefit the vitality of the oaks.

PMID- 21961042
TI  - Transgene excision has no impact on in vivo integration of human iPS derived
      neural precursors.
AB  - The derivation of induced human pluripotent stem cells (hiPS) has generated
      significant enthusiasm particularly for the prospects of cell-based therapy. But
      there are concerns about the suitability of iPS cells for in vivo applications
      due in part to the introduction of potentially oncogenic transcription factors
      via viral vectors. Recently developed lentiviral vectors allow the excision of
      viral reprogramming factors and the development of transgene-free iPS lines.
      However it is unclear if reprogramming strategy has an impact on the
      differentiation potential and the in vivo behavior of hiPS progeny. Here we
      subject viral factor-free, c-myc-free and conventionally reprogrammed four-factor
      human iPS lines to a further challenge, by analyzing their differentiation
      potential along the 3 neural lineages and over extended periods of time in vitro,
      as well as by interrogating their ability to respond to local environmental cues
      by grafting into the striatum. We demonstrate similar and efficient
      differentiation into neurons, astrocytes and oligodendrocytes among all hiPS and
      human ES line controls. Upon intracranial grafting in the normal rat (Sprague
      Dawley), precursors derived from all hiPS lines exhibited good survival and
      response to environmental cues by integrating into the subventricular zone,
      acquiring phenotypes typical of type A, B or C cells and migrating along the
      rostral migratory stream into the olfactory bulb. There was no teratoma or other
      tumor formation 12 weeks after grafting in any of the 26 animals used in the
      study. Thus neither factor excision nor persistence of c-myc impact the behavior
      of hiPS lines in vivo.

PMID- 21961044
TI  - Erk1 positively regulates osteoclast differentiation and bone resorptive
      activity.
AB  - The extracellular signal-regulated kinases (ERK1 and 2) are widely-expressed and
      they modulate proliferation, survival, differentiation, and protein synthesis in
      multiple cell lineages. Altered ERK1/2 signaling is found in several genetic
      diseases with skeletal phenotypes, including Noonan syndrome, Neurofibromatosis
      type 1, and Cardio-facio-cutaneous syndrome, suggesting that MEK-ERK signals
      regulate human skeletal development. Here, we examine the consequence of Erk1 and
      Erk2 disruption in multiple functions of osteoclasts, specialized
      macrophage/monocyte lineage-derived cells that resorb bone. We demonstrate that
      Erk1 positively regulates osteoclast development and bone resorptive activity, as
      genetic disruption of Erk1 reduced osteoclast progenitor cell numbers,
      compromised pit formation, and diminished M-CSF-mediated adhesion and migration.
      Moreover, WT mice reconstituted long-term with Erk1(-/-) bone marrow mononuclear
      cells (BMMNCs) demonstrated increased bone mineral density as compared to
      recipients transplanted with WT and Erk2(-/-) BMMNCs, implicating marrow
      autonomous, Erk1-dependent osteoclast function. These data demonstrate Erk1 plays
      an important role in osteoclast functions while providing rationale for the
      development of Erk1-specific inhibitors for experimental investigation and/or
      therapeutic modulation of aberrant osteoclast function.

PMID- 21961043
TI  - Bound water at protein-protein interfaces: partners, roles and hydrophobic
      bubbles as a conserved motif.
AB  - BACKGROUND: There is a great interest in understanding and exploiting protein
      protein associations as new routes for treating human disease. However, these
      associations are difficult to structurally characterize or model although the
      number of X-ray structures for protein-protein complexes is expanding. One
      feature of these complexes that has received little attention is the role of
      water molecules in the interfacial region. METHODOLOGY: A data set of 4741 water
      molecules abstracted from 179 high-resolution (<= 2.30 A) X-ray crystal
      structures of protein-protein complexes was analyzed with a suite of modeling
      tools based on the HINT forcefield and hydrogen-bonding geometry. A metric termed
      Relevance was used to classify the general roles of the water molecules. RESULTS:
      The water molecules were found to be involved in: a) (bridging) interactions with
      both proteins (21%), b) favorable interactions with only one protein (53%), and
      c) no interactions with either protein (26%). This trend is shown to be
      independent of the crystallographic resolution. Interactions with residue
      backbones are consistent for all classes and account for 21.5% of all
      interactions. Interactions with polar residues are significantly more common for
      the first group and interactions with non-polar residues dominate the last group.
      Waters interacting with both proteins stabilize on average the proteins'
      interaction (-0.46 kcal mol(-1)), but the overall average contribution of a
      single water to the protein-protein interaction energy is unfavorable (+0.03 kcal
      mol(-1)). Analysis of the waters without favorable interactions with either
      protein suggests that this is a conserved phenomenon: 42% of these waters have
      SASA <= 10 A(2) and are thus largely buried, and 69% of these are within
      predominantly hydrophobic environments or "hydrophobic bubbles". Such water
      molecules may have an important biological purpose in mediating protein-protein
      interactions.

PMID- 21961045
TI  - Analytical performance of the Roche LightCycler(r) Mycobacterium Detection Kit
      for the diagnosis of clinically important mycobacterial species.
AB  - BACKGROUND: The LightCycler(r) Mycobacterium Detection Kit based on real-time PCR
      technology for the detection of Mycobacterium tuberculosis, Mycobacterium avium
      and Mycobacterium kansasii was recently developed. This study evaluated its
      analytical sensitivity, specificity and reproducibility. METHODOLOGY/PRINCIPAL
      FINDINGS: Plasmid standards were prepared and used to determine the limit of
      detection. The assay was also performed against organisms other than
      mycobacteria, other mycobacterial strains and interfering substances to exclude
      cross-reactivity and interference. Reference standards were prepared and tested
      to assess the assay's reproducibility. All PCR assays were performed using the
      LightCycler(r) 2.0 Instrument. The detection limit for M. tuberculosis was 28
      copies per microlitre. Neither cross-reactivity nor interference occurred with
      non-mycobacterial organisms and substances tested. Overall reproducibility for
      consecutive measurements, run-to-run, lot-to-lot, day-to-day and laboratory-to
      laboratory achieved a coefficient of variance of less than two percent.
      SIGNIFICANCE: The LightCycler(r) Mycobacterium Detection kit has shown to be a
      robust and accurate assay with the potential to be used as a rapid TB diagnostic
      test.

PMID- 21961046
TI  - Direct in vivo evidence for tumor propagation by glioblastoma cancer stem cells.
AB  - High-grade gliomas (World Health Organization grade III anaplastic astrocytoma
      and grade IV glioblastoma multiforme), the most prevalent primary malignant brain
      tumors, display a cellular hierarchy with self-renewing, tumorigenic cancer stem
      cells (CSCs) at the apex. While the CSC hypothesis has been an attractive model
      to describe many aspects of tumor behavior, it remains controversial due to
      unresolved issues including the use of ex vivo analyses with differential growth
      conditions. A CSC population has been confirmed in malignant gliomas by
      preferential tumor formation from cells directly isolated from patient biopsy
      specimens. However, direct comparison of multiple tumor cell populations with
      analysis of the resulting phenotypes of each population within a representative
      tumor environment has not been clearly described. To directly test the relative
      tumorigenic potential of CSCs and non-stem tumor cells in the same
      microenvironment, we interrogated matched tumor populations purified from a
      primary human tumor transplanted into a xenograft mouse model and monitored
      competitive in vivo tumor growth studies using serial in vivo intravital
      microscopy. While CSCs were a small minority of the initial transplanted cancer
      cell population, the CSCs, not the non-stem tumor cells, drove tumor formation
      and yielded tumors displaying a cellular hierarchy. In the resulting tumors, a
      fraction of the initial transplanted CSCs maintained expression of stem cell and
      proliferation markers, which were significantly higher compared to the non-stem
      tumor cell population and demonstrated that CSCs generated cellular heterogeneity
      within the tumor. These head-to-head comparisons between matched CSCs and non
      stem tumor cells provide the first functional evidence using live imaging that in
      the same microenvironment, CSCs more than non-stem tumor cells are responsible
      for tumor propagation, confirming the functional definition of a CSC.

PMID- 21961048
TI  - Culturing pancreatic islets in microfluidic flow enhances morphology of the
      associated endothelial cells.
AB  - Pancreatic islets are heavily vascularized in vivo with each insulin secreting
      beta-cell associated with at least one endothelial cell (EC). This structure is
      maintained immediately post-isolation; however, in culture the ECs slowly
      deteriorate, losing density and branched morphology. We postulate that this
      deterioration occurs in the absence of blood flow due to limited diffusion of
      media inside the tissue. To improve exchange of media inside the tissue, we
      created a microfluidic device to culture islets in a range of flow-rates.
      Culturing the islets from C57BL6 mice in this device with media flowing between 1
      and 7 ml/24 hr resulted in twice the EC-density and -connected length compared to
      classically cultured islets. Media containing fluorescent dextran reached the
      center of islets in the device in a flow-rate-dependant manner consistent with
      improved penetration. We also observed deterioration of EC morphology using serum
      free media that was rescued by addition of bovine serum albumin, a known anti
      apoptotic signal with limited diffusion in tissue. We further examined the effect
      of flow on beta-cells showing dampened glucose-stimulated Ca(2+)-response from
      cells at the periphery of the islet where fluid shear-stress is greatest.
      However, we observed normal two-photon NAD(P)H response and insulin secretion
      from the remainder of the islet. These data reveal the deterioration of islet EC
      morphology is in part due to restricted diffusion of serum albumin within the
      tissue. These data further reveal microfluidic devices as unique platforms to
      optimize islet culture by introducing intercellular flow to overcome the
      restricted diffusion of media components.

PMID- 21961047
TI  - Profiling of the tetraspanin CD151 web and conspiracy of CD151/integrin beta1
      complex in the progression of hepatocellular carcinoma.
AB  - Tetraspanin CD151 has been implicated in metastasis through forming complexes
      with different molecular partners. In this study, we mapped tetraspanin web
      proteins centered on CD151, in order to explore the role of CD151 complexes in
      the progression of hepatocellular carcinoma (HCC). Immunoprecipitation was used
      to isolate tetraspanin complexes from HCCLM3 cells using a CD151 antibody, and
      associated proteins were identified by mass spectrometry. The interaction of
      CD151 and its molecular partners, and their roles in invasiveness and metastasis
      of HCC cells were assayed through disruption of the CD151 network. Finally, the
      clinical implication of CD151 complexes in HCC patients was also examined. In
      this study, we identified 58 proteins, characterized the tetraspanin CD151 web,
      and chose integrin beta1 as a main partner to further investigate. When the
      CD151/integrin beta1 complex in HCC cells was disrupted, migration, invasiveness,
      secretion of matrix metalloproteinase 9, and metastasis were markedly influenced.
      However, both CD151 and integrin beta1 expression were untouched. HCC patients
      with high expression of CD151/integrin beta1 complex had the poorest prognosis of
      the whole cohort of patients. Together, our data show that CD151 acts as an
      important player in the progression of HCC in an integrin beta1-dependent manner.

PMID- 21961049
TI  - OsWRKY IIa Transcription Factors Modulate Rice Innate Immunity.
AB  - WRKY transcription factors regulate diverse plant processes including responses
      to biotic stresses. Our previous studies indicate that OsWRKY62, an OsWRKY IIa
      subfamily member, functions as a negative regulator of the rice defense against
      Xanthomonas oryzae pv. oryzae. Here, we report that a large inverted repeat
      construct designed to knock down the expression of the four OsWRKY IIa subfamily
      members (OsWRKY62, OsWRKY28, OsWRKY71, and OsWRKY76) leads to overexpression of
      all four genes and disease resistance in some transgenic plants. These phenotypes
      are stably inherited as reflected by progeny analysis. A pathogenesis-related
      gene, PR10, is up-regulated in plants overexpressing the OsWRKY IIa genes. These
      results suggest that OsWRKY IIa proteins interact functionally to modulate plant
      innate immunity.

PMID- 21961050
TI  - Effect of novel marine nutraceuticals on IL-1alpha-mediated TNF-alpha release
      from UVB-irradiated human melanocyte-derived cells.
AB  - UV-induced inflammation and reactive oxygen species formation are involved in the
      development of melanoma. Natural products like 5beta-scymnol and CO(2)
      supercritical fluid extract (CO(2)-SFE) of mussel oil contain anti-inflammatory
      and antioxidant properties that may aid in reducing the deleterious effects of UV
      radiation. Therefore, their effect on the release of the proinflammatory
      cytokine, tumour necrosis factor-alpha (TNF-alpha), from UVB-irradiated human
      melanocytic cells was examined. Human epidermal melanocytes (HEM) and MM96L
      melanoma cells were exposed to UVB radiation and IL-1alpha. Cell viability and
      TNF-alpha levels were determined 24 hours after-irradiation while p38 mitogen
      activated protein kinase (MAPK) activation was observed at 15 min after
      irradiation. When alpha-tocopherol, CO(2)-SFE mussel oil, and 5beta-scymnol were
      added to the UVB-irradiated HEM cells treated with IL-1alpha, TNF-alpha levels
      fell by 53%, 65%, and 76%, respectively, while no inhibition was evident in MM96L
      cells. This effect was not due to inhibition of the intracellular p38 MAPK
      signalling pathway. These compounds may be useful in preventing inflammation
      induced damage to normal melanocytes.

PMID- 21961051
TI  - Discovery and characterization of novel subtype-selective allosteric agonists for
      the investigation of M(1) receptor function in the central nervous system.
AB  - Cholinergic transmission in the forebrain is mediated primarily by five subtypes
      of muscarinic acetylcholine receptors (mAChRs), termed M(1)-M(5). Of the mAChR
      subtypes, M(1) is among the most heavily expressed in regions that are critical
      for learning and memory, and has been viewed as the most critical mAChR subtype
      for memory and attention mechanisms. Unfortunately, it has been difficult to
      develop selective activators of M(1) and other individual mAChR subtypes, which
      has prevented detailed studies of the functional roles of selective activation of
      M(1). Using a functional HTS screen and subsequent diversity-oriented synthesis
      approach we have discovered a novel series of highly selective M(1) allosteric
      agonists. These compounds activate M(1) with EC(50) values in the 150 nM to 500
      nM range and have unprecedented, clean ancillary pharmacology (no substantial
      activity at 10MUM across a large panel of targets). Targeted mutagenesis revealed
      a potentially novel allosteric binding site in the third extracellular loop of
      the M(1) receptor for these allosteric agonists. Optimized compounds, such as
      VU0357017, provide excellent brain exposure after systemic dosing and have robust
      in vivo efficacy in reversing scopolamine-induced deficits in a rodent model of
      contextual fear conditioning. This series of selective M(1) allosteric agonists
      provides critical research tools to allow dissection of M(1)-mediated effects in
      the CNS and potential leads for novel treatments for Alzheimer's disease and
      schizophrenia.

PMID- 21961052
TI  - Molecular Microscopy of Brain Gangliosides: Illustrating their Distribution in
      Hippocampal Cell Layers.
AB  - Gangliosides are amphiphilic molecules found in the outer layer of plasma
      membranes of all vertebrate cells. They play a major role in cell recognition and
      signaling and are involved in diseases affecting the central nervous system
      (CNS). We are reporting the differential distribution of ganglioside species in
      the rat brain's cerebrum, based on their ceramide associated core, and for the
      first time the presence of acetylation detected by matrix-assisted laser
      desorption/ionization (MALDI) mass spectrometry, which was used to map and image
      gangliosides with detailed structural information and histological accuracy. In
      the hippocampus, localization of the major species GM1, GD1, O-acetylGD1, GT1,
      and O-acetylGT1 depends on the sphingoid base (d18:1 sphingosine or d20:1
      eicosasphingosine) in the molecular layer of the dentate gyrus (ML), which is
      made up of three distinct layers, the inner molecular layer (IML), which contains
      sphingosine exclusively, and the middle molecular layer (MML) and the outer
      molecular layer (OML) where eicosasphingosine is the only sphingoid base. These
      results demonstrate that there is a different distribution of gangliosides in
      neuronal axons and dendrites depending on the ceramide core of each layer. GM3,
      GM2, GD3, and GD2 contain sphingosine predominantly and are mainly present in
      body cell layers, which are made up of the pyramidal cell layer (Py) and the
      granular layer of the dentate gyrus (GL), in contrast with GQ1 and the O
      acetylated forms of GD1, GT1, and GQ1 gangliosides, which contain both sphingoid
      bases. However their distribution is based on the sialylated and acetylated
      oligosaccharide chains in the neuronal cell bodies.

PMID- 21961053
TI  - Prevention of Prostate Cancer with Oleanane Synthetic Triterpenoid CDDO-Me in the
      TRAMP Mouse Model of Prostate Cancer.
AB  - 2-Cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO), a synthetic analog of
      oleanolic acid, and its C28 methyl ester derivative (CDDO-Me), have shown potent
      antitumorigenic activity against a wide range of cancer cell lines, including
      prostate cancer cells in vitro, and inhibited the development of liver and lung
      cancer in vivo. In the present study, we examined the efficacy of CDDO-Me in
      preventing the development and progression of prostate cancer in the transgenic
      adenocarinoma of the mouse prostate (TRAMP) model. CDDO-Me inhibited the growth
      of murine TRAMPC-1 prostate cancer cells by inducing apoptosis through the
      inhibition of antiapoptotic p-Akt, p-mTOR and NF-kappaB. Early intervention with
      CDDO-Me (7.5 mg/kg) initiated at five weeks of age for 20 wk inhibited the
      progression of the preneoplastic lesions (low-grade PIN and high-grade-PIN) to
      adenocarcinoma in the dorsolateral prostate (DLP) and ventral prostate (VP) lobes
      of TRAMP mice. Even delayed administration of CDDO-Me started at 12 wk of age for
      12 wk inhibited the development of adenocarcimona of the prostate. Both early and
      late treatment with CDDO-Me inhibited the metastasis of tumor to the distant
      organs. Treatment with CDDO-Me inhibited the expression of prosurvival p-Akt and
      NF-kappaB in the prostate and knocking-down Akt in TRAMPC-1 tumor cells
      sensitized them to CDDO-Me. These findings indicated that Akt is a target for
      apoptoxicity in TRAMPC-1 cells in vitro and potentially a target of CDDO-Me for
      inhibition of prostate cancer in vivo. 

PMID- 21961054
TI  - Site-selective artificial ribonucleases: oligonucleotide conjugates containing
      multiple imidazole residues in the catalytic domain.
AB  - Design of site-selective artificial ribonucleases (aRNases) is one of the most
      challenging tasks in RNA targeting. Here, we designed and studied oligonucleotide
      based aRNases containing multiple imidazole residues in the catalytic part and
      systematically varied structure of cleaving constructs. We demonstrated that the
      ribonuclease activity of the conjugates is strongly affected by the number of
      imidazole residues in the catalytic part, the length of a linker between the
      catalytic imidazole groups of the construct and the oligonucleotide, and the type
      of anchor group, connecting linker structure and the oligonucleotide. Molecular
      modeling of the most active aRNases showed that preferable orientation(s) of
      cleaving constructs strongly depend on the structure of the anchor group and
      length of the linker. The inclusion of deoxyribothymidine anchor group
      significantly reduced the probability of cleaving groups to locate near the
      cleavage site, presumably due to a stacking interaction with the neighbouring
      nucleotide residue. Altogether the obtained results show that dynamics factors
      play an important role in site-specific RNA cleavage. Remarkably high cleavage
      activity was displayed by the conjugates with the most flexible and extended
      cleaving construct, which presumably provides a better opportunity for imidazole
      residues to be correctly positioned in the vicinity of scissile phosphodiester
      bond.

PMID- 21961056
TI  - Inflammation and epstein-barr virus infection are common features of myasthenia
      gravis thymus: possible roles in pathogenesis.
AB  - The thymus plays a major role in myasthenia gravis (MG). Our recent finding of a
      persistent Epstein-Barr (EBV) virus infection in some MG thymuses, combined with
      data showing that the thymus is in a proinflammatory state in most patients,
      supports a viral contribution to the pathogenesis of MG. Aim of this study was to
      gain further evidence for intrathymic chronic inflammation and EBV infection in
      MG patients. Transcriptional profiling by low density array and real-time PCR
      showed overexpression of genes involved in inflammatory and immune response in MG
      thymuses. Real-time PCR for EBV genome, latent (EBER1, EBNA1, LMP1) and lytic
      (BZLF1) transcripts, and immunohistochemistry for LMP1 and BZLF1 proteins
      confirmed an active intrathymic EBV infection, further supporting the hypothesis
      that EBV might contribute to onset or perpetuation of the autoimmune response in
      MG. Altogether, our results support a role of inflammation and EBV infection as
      pathogenic features of MG thymus.

PMID- 21961055
TI  - Biochemical and molecular aspects of vascular adrenergic regulation of blood
      pressure in the elderly.
AB  - Hypertension, orthostatic hypotension, arterial insufficiency, and
      atherosclerosis are common disorders in the elderly that lead to significant
      morbidity and mortality. One common factor to these conditions is an age-related
      decline in vascular beta-adrenergic receptor-mediated function and subsequent
      cAMP generation. Presently, there is no single cellular factor that can explain
      this age-related decline, and thus, the primary cause of this homeostatic
      imbalance is yet to be identified. However, the etiology is clearly associated
      with an age-related change in the ability of beta-adrenergic receptor to respond
      to agonist at the cellular level in the vasculature. This paper will review what
      is presently understood regarding the molecular and biochemical basis of age
      impaired beta-adrenergic receptor-mediated signaling. A fundamental understanding
      of why beta-AR-mediated vasorelaxation is impaired with age will provide new
      insights and innovative strategies for the management of multiple clinical
      disorders.

PMID- 21961057
TI  - Anaesthetic considerations in paediatric myasthenia gravis.
AB  - Myasthenia gravis is of particular interest to anaesthetists because of the
      muscle groups affected, the pharmacology of the neuromuscular junction, and
      interaction of both the disease and treatment with many anaesthetic drugs.
      Anaesthetists may encounter children with myasthenia either to facilitate
      treatment options or to institute mechanical ventilation in the face of a crisis.
      This paper reviews the literature pertaining to the pathophysiology and applied
      pharmacology of the disease and explores the relationship between these and the
      anaesthetic management. In addition to illustrating the tried-and-tested
      techniques, some newer management options are explored.

PMID- 21961058
TI  - Unraveling the Relationship between Smoking and Weight: The Role of Sedentary
      Behavior.
AB  - Research has shown that current smokers have a lower mean body mass index (BMI)
      than never and former smokers, with former smokers having the highest mean BMI. A
      number of physiological mechanisms have been hypothesized to explain this
      pattern, but few studies have explored the possible role of behavioral factors.
      Using data from the cross-sectional National Health and Nutrition Examination
      Survey 1999-2006, this descriptive study explored the associations among smoking
      status, sedentary behavior, and two anthropometric measures (BMI and waist
      circumference (WC)). Sedentary behavior was significantly higher among current
      smokers compared to never and former smokers; former smokers had higher levels of
      sedentary behavior compared to never smokers. The association between smoking
      status and anthropometric outcomes was moderated by sedentary behavior, with
      current smokers evidencing higher BMI and WC at higher levels of sedentary
      behavior compared to lower levels of sedentary behavior. Results are discussed in
      terms of their implications for interventions, particularly with respect to
      postcessation weight gain.

PMID- 21961059
TI  - Combinational Effects of Prebiotics and Soybean against Azoxymethane-Induced
      Colon Cancer  In Vivo.
AB  - Prebiotic fructans are nondigestible carbohydrates with numerous health benefits.
      Soybean is a rich source of phytonutrients such as isoflavones. The objective of
      this study was to evaluate the chemopreventive effects of prebiotics (Synergy1)
      and soybean meal (SM) at 5% and 10% levels alone and in combination on
      azoxymethane- (AOM-) induced colon carcinogenesis. After one wk of
      acclimatization, Fisher 344 male rats (N = 90) were randomly assigned to 9 groups
      (n = 10). Control rats (C) were fed AIN-93G/M. Two s/c injections of AOM were
      administered to rats at 7 and 8 wk of age at 16 mg/kg body weight. Rats were
      killed by CO(2) asphyxiation at 45 wk. Tumor incidence (%) in treatment groups
      ranged from 40 to 75 compared to 100 in C. Results indicate that feeding
      prebiotics and soybean in combination significantly reduced incidence of AOM
      induced colon tumors with implications for food industry in the food-product
      development.

PMID- 21961060
TI  - Depression among Asian Americans: Review and Recommendations.
AB  - This article presents a review of the prevalence and manifestation of depression
      among Asian Americans and discusses some of the existing issues in the assessment
      and diagnosis of depression among Asian Americans. The authors point out the
      diversity and increasing numbers of Asian Americans and the need to provide
      better mental health services for this population. While the prevalence of
      depression among Asian Americans is lower than that among other ethnic/racial
      groups, Asian Americans receive treatment for depression less often and its
      quality is less adequate. In addition, the previous belief that Asians somatize
      depression may become obsolete as more evidence appears to support that
      Westerners may "psychologize" depression. The cultural validity of the current
      DSM-IV conceptualization of depression is questioned. In the course of the
      review, the theme of complexity emerges: the heterogeneity of ethnic Asian
      American groups, the multidimensionality of depression, and the intersectionality
      of multiple factors among depressed Asian Americans.

PMID- 21961061
TI  - Self-referential thinking, suicide, and function of the cortical midline
      structures and striatum in mood disorders: possible implications for treatment
      studies of mindfulness-based interventions for bipolar depression.
AB  - Bipolar depression is often refractory to treatment and is frequently associated
      with anxiety symptoms and elevated suicide risk. There is a great need for
      adjunctive psychotherapeutic interventions. Treatments with effectiveness for
      depressive and anxiety symptoms as well as suicide-related thoughts and behaviors
      would be particularly beneficial. Mindfulness-based interventions hold promise,
      and studies of these approaches for bipolar disorder are warranted. The aim of
      this paper is to provide a conceptual background for such studies by reviewing
      key findings from diverse lines of investigation. Results of that review indicate
      that cortical midline structures (CMS) appear to link abnormal self-referential
      thinking to emotional dysregulation in mood disorders. Furthermore, CMS and
      striatal dysfunction may play a role in the neuropathology underlying suicide
      related thoughts and behaviors. Thus, combining studies of mindfulness
      interventions targeting abnormal self-referential thinking with functional
      imaging of CMS and striatal function may help delineate the neurobiological
      mechanisms of action of these treatments.

PMID- 21961062
TI  - Functional outcome in bipolar disorder: the big picture.
AB  - Previous research on functional outcome in bipolar disorder (BD) has uncovered
      various factors that exacerbate psychosocial disability over the course of
      illness, including genetics, illness severity, stress, anxiety, and cognitive
      impairment. This paper presents an integrated view of these findings that
      accounts for the precipitous decline in psychosocial functioning after illness
      onset. The proposed model highlights a number of reciprocal pathways among
      previously studied factors that trap people in a powerful cycle of ailing forces.
      The paper discusses implications to patient care as well as the larger social
      changes required for shifting the functional trajectory of people with BD from
      psychosocial decline to growth.

PMID- 21961064
TI  - Balance, sensorimotor, and cognitive performance in long-year expert senior
      ballroom dancers.
AB  - Physical fitness is considered a major factor contributing to the maintenance of
      independent living and everyday competence. In line with this notion, it has been
      shown that several years of amateur dancing experience can exert beneficial
      effects not only on balance and posture but also on tactile, motor, and cognitive
      functions in older people. This raises the question of whether an even more
      extensive schedule of dancing, including competitive tournaments, would further
      enhance these positive effects. We therefore assessed posture, balance, and
      reaction times, as well as motor, tactile, and cognitive performance in older
      expert ballroom dancers with several years of competitive experience. We found
      substantially better performance in the expert group than in the controls in
      terms of expertise-related domains like posture, balance, and reaction times.
      However, there was no generalization of positive effects to those domains that
      were found to be improved in amateur dancers, such as tactile and cognitive
      performance, suggesting that there might be an optimal range of intervention
      intensity to maintain health and independence throughout the human lifespan.

PMID- 21961063
TI  - Evidence for the role of B cells and immunoglobulins in the pathogenesis of
      multiple sclerosis.
AB  - The pathogenesis of multiple sclerosis (MS) remains elusive. Recent reports
      advocate greater involvement of B cells and immunoglobulins in the initiation and
      propagation of MS lesions at different stages of their ontogeny. The key role of
      B cells and immunoglobulins in pathogenesis was initially identified by studies
      in which patients whose fulminant attacks of demyelination did not respond to
      steroids experienced remarkable functional improvement following plasma exchange.
      The positive response to Rituximab in Phase II clinical trials of relapsing
      remitting MS confirms the role of B cells. The critical question is how B cells
      contribute to MS. In this paper, we discuss both the deleterious and the
      beneficial roles of B cells and immunoglobulins in MS lesions. We provide
      alternative hypotheses to explain both damaging and protective antibody
      responses.

PMID- 21961066
TI  - Do Stress Trajectories Predict Mortality in Older Men? Longitudinal Findings from
      the VA Normative Aging Study.
AB  - We examined long-term patterns of stressful life events (SLE) and their impact on
      mortality contrasting two theoretical models: allostatic load (linear
      relationship) and hormesis (inverted U relationship) in 1443 NAS men (aged 41-87
      in 1985; M = 60.30, SD = 7.3) with at least two reports of SLEs over 18 years
      (total observations = 7,634). Using a zero-inflated Poisson growth mixture model,
      we identified four patterns of SLE trajectories, three showing linear decreases
      over time with low, medium, and high intercepts, respectively, and one an
      inverted U, peaking at age 70. Repeating the analysis omitting two health-related
      SLEs yielded only the first three linear patterns. Compared to the low-stress
      group, both the moderate and the high-stress groups showed excess mortality,
      controlling for demographics and health behavior habits, HRs = 1.42 and 1.37, ps
      <.01 and <.05. The relationship between stress trajectories and mortality was
      complex and not easily explained by either theoretical model.

PMID- 21961065
TI  - Pathways to aging: the mitochondrion at the intersection of biological and
      psychosocial sciences.
AB  - Compelling evidence suggests that both biological and psychosocial factors impact
      the process of aging. However, our understanding of the dynamic interplay among
      biological and psychosocial factors across the life course is still fragmentary.
      For example, it needs to be established how the interaction of individual factors
      (e.g., genetic and epigenetic endowment and personality), behavioral factors
      (e.g., physical activity, diet, and stress management), and psychosocial
      experiences (e.g., social support, well-being, socioeconomic status, and
      marriage) in perinatal, childhood, and adulthood influence health across the
      aging continuum. This paper aims to outline potential intersection points serving
      as an interface between biological and psychosocial factors, with an emphasis on
      the mitochondrion. Mitochondria are cellular organelles which play a critical
      role in cellular senescence. Both chronic exposure to psychosocial stress and
      genetic-based mitochondrial dysfunction have strikingly similar biological
      consequences; both predispose individuals to adverse age-related health disorders
      and early mortality. Exploring the interactive nature of the factors resulting in
      pathways to normal healthy aging, as well as those leading to morbidity and early
      mortality, will continue to enhance our ability to translate research into
      effective practices that can be implemented throughout the life course to
      optimise the aging process.

PMID- 21961067
TI  - Propensity score-matched analysis of open surgical and endovascular repair for
      type B aortic dissection.
AB  - Objective. To identify national outcomes of thoracic endovascular aortic repair
      (TEVAR) for type B aortic dissections (TBADs). Methods. The Nationwide Inpatient
      Sample database was examined from 2005 to 2008 using ICD-9 codes to identify
      patients with TBAD who underwent TEVAR or open surgical repair. We constructed
      separate propensity models for emergently and electively admitted patients and
      calculated mortality and complication rates for propensity score-matched cohorts
      of TEVAR and open repair patients. Results. In-hospital mortality was
      significantly higher following open repair than TEVAR (17.5% versus 10.8%, P =
      .045) in emergently admitted TBAD. There was no in-hospital mortality difference
      between open repair and TEVAR (5.6% versus 3.3%, P = .464) for elective
      admissions. Hospitals performing thirty or more TEVAR procedures annually had
      lower mortality for emergent TBAD than hospitals with fewer than thirty
      procedures. Conclusions. TEVAR produces better in-hospital outcomes in emergent
      TBAD than open repair, but further longitudinal analysis is required.

PMID- 21961068
TI  - The effect of alcohol on postprandial and fasting triglycerides.
AB  - Alcohol has a significant additive effect on the postprandial triglyceride peak
      when it accompanies a meal containing fat, especially saturated fat. This results
      from a decrease in the breakdown of chylomicrons and VLDL remnants due to an
      acute inhibitory effect of alcohol on lipoprotein lipase activity. Furthermore,
      alcohol increases the synthesis of large VLDL particles in the liver, which is
      the main source of triglycerides in the hypertriglyceridemia associated with
      chronic excessive alcohol intake. In case of chronic consumption, lipoprotein
      lipase activity seems to adapt itself. The effect of alcohol on adipose tissues
      is less clear. Sometimes, a severe hypertriglyceridemia induced by alcohol
      (SHIBA) can be observed, especially in patients with type 2 diabetes mellitus
      and/or obesity increasing the risk of pancreatitis.

PMID- 21961069
TI  - The oxidative state of chylomicron remnants influences their modulation of human
      monocyte activation.
AB  - Chylomicron remnants (CMRs) contribute directly to human monocyte activation in
      vitro, by increasing reactive oxygen species (ROS) production and cell migration.
      In this study, the effects of the oxidative state of CMR on the degree of
      monocyte activation was investigated. CMR-like particles (CRLPs) were prepared in
      three different oxidative states, normal (CRLPs), protected from oxidation by
      incorporation of the antioxidant, probucol (pCRLPs), or oxidised with CuSO(4)
      (oxCRLPs). Lipid accumulation and ROS production were significantly increased in
      primary human monocytes incubated with CRLPs, whilst secretion on monocyte
      chemoattractant protein-1 was reduced, but oxCRLPs had no additional effect. In
      contrast, pCRLPs were taken up by monocytes to a lesser extent and had no
      significant effect on ROS or MCP-1 secretion. These studies suggest that the
      oxidative state of CMRs modulates their stimulation of the activation of
      peripheral blood human monocytes and that dietary antioxidants may provide some
      protection against these atherogenic effects.

PMID- 21961071
TI  - Visceral abdominal and subfascial femoral adipose tissue have opposite
      associations with liver fat in overweight and obese premenopausal caucasian
      women.
AB  - Abdominal obesity has been associated with liver fat storage. However, the
      relationships between other body composition depots and metabolic syndrome
      features with hepatic fat are still unclear. We examined abdominal and thigh
      adipose tissue (AT) compartments associations with liver fat in 140 overweight
      and obese premenopausal Caucasian women. Blood lipids and, proinflammatory and
      atherothrombotic markers associations with hepatic fat were also analyzed. A
      larger visceral AT (VAT) was related with liver fat (P < 0.05). Contrarily, thigh
      subfascial AT was inversely related to liver fat (P < 0.05). Increased fasting
      insulin, triglycerides, PAI-1 concentrations, and a higher total-cholesterol/HDL
      cholesterol ratio were also associated with hepatic fat, even after adjustment
      for VAT (P < 0.05). Thigh subfascial adiposity was inversely associated with
      liver fat, suggesting a potential preventive role against ectopic fat storage in
      overweight and obese women. These results reinforce the contribution of an
      abdominal obesity phenotype associated with a diabetogenic and atherothrombotic
      profile to liver lipotoxicity.

PMID- 21961070
TI  - Understanding postprandial inflammation and its relationship to lifestyle
      behaviour and metabolic diseases.
AB  - Postprandial hyperlipidemia with accumulation of remnant lipoproteins is a common
      metabolic disturbance associated with atherosclerosis and vascular dysfunction,
      particularly during chronic disease states such as obesity, the metabolic
      syndrome and, diabetes. Remnant lipoproteins become attached to the vascular
      wall, where they can penetrate intact endothelium causing foam cell formation.
      Postprandial remnant lipoproteins can activate circulating leukocytes, upregulate
      the expression of endothelial adhesion molecules, facilitate adhesion and
      migration of inflammatory cells into the subendothelial space, and activate the
      complement system. Since humans are postprandial most of the day, the continuous
      generation of remnants after each meal may be one of the triggers for the
      development of atherosclerosis. Modulation of postprandial lipemia by lifestyle
      changes and pharmacological interventions could result in a further decrease of
      cardiovascular mortality and morbidity. This paper will provide an update on
      current concepts concerning the relationship between postprandial lipemia,
      inflammation, vascular function, and therapeutic options.

PMID- 21961072
TI  - Associative memory storage and retrieval: involvement of theta oscillations in
      hippocampal information processing.
AB  - Theta oscillations are thought to play a critical role in neuronal information
      processing, especially in the hippocampal region, where their presence is
      particularly salient. A detailed description of theta dynamics in this region has
      revealed not only a consortium of layer-specific theta dipoles, but also within
      layer differences in the expression of theta. This complex and articulated
      arrangement of current flows is reflected in the way neuronal firing is modulated
      in time. Several models have proposed that these different theta modulators
      flexibly coordinate hippocampal regions, to support associative memory formation
      and retrieval. Here, we summarily review different approaches related to this
      issue and we describe a mechanism, based on experimental and simulation results,
      for memory retrieval in CA3 involving theta modulation.

PMID- 21961074
TI  - The emerging epidemic of obesity, diabetes, and the metabolic syndrome in china.
AB  - China is one of the fastest developing countries in the world. Rapid economic
      progress has resulted in changes to both diet and physical activity. New found
      prosperity, increased urban migration, and the adoption of sedentary lifestyles
      by an aging Chinese population have resulted in a dramatic shift in disease
      burden-from infectious to chronic. Modern Chinese find themselves increasingly
      afflicted with the same noncommunicable chronic diseases typical of
      industrialized nations. Today, cardiovascular disease is the number one cause of
      both morbidity and mortality, affecting both rural and urban Chinese. The rising
      incidence of cardiovascular disease has been fueled by an epidemic of
      cardiometabolic risk factors. While hypertension and smoking have received
      considerable spotlight, little attention has been given to obesity, diabetes, and
      metabolic syndrome. Their increasing prevalence is the focus of this paper.

PMID- 21961075
TI  - Site-Specific Insertion Polymorphism of the MITE Alex-1 in the Genus Coffea
      Suggests Interspecific Gene Flow.
AB  - Miniature Inverted-repeat Transposable Elements (MITEs) are small nonautonomous
      class-II transposable elements distributed throughout eukaryotic genomes. We
      identified a novel family of MITEs (named Alex) in the Coffea canephora genome
      often associated with expressed sequences. The Alex-1 element is inserted in an
      intron of a gene at the CcEIN4 locus. Its mobility was demonstrated by sequencing
      the insertion site in C. canephora accessions and Coffea species. Analysis of the
      insertion polymorphism of Alex-1 at this locus in Coffea species and in C.
      canephora showed that there was no relationship between the geographical
      distribution of the species, their phylogenetic relationships, and insertion
      polymorphism. The intraspecific distribution of C. canephora revealed an original
      situation within the E diversity group. These results suggest possibly greater
      gene flow between species than previously thought. This MITE family will enable
      the study of the C. canephora genome evolution, phylogenetic relationships, and
      possible gene flows within the Coffea genus.

PMID- 21961073
TI  - Ripples make waves: binding structured activity and plasticity in hippocampal
      networks.
AB  - Establishing novel episodic memories and stable spatial representations depends
      on an exquisitely choreographed, multistage process involving the online encoding
      and offline consolidation of sensory information, a process that is largely
      dependent on the hippocampus. Each step is influenced by distinct neural network
      states that influence the pattern of activation across cellular assemblies. In
      recent years, the occurrence of hippocampal sharp wave ripple (SWR) oscillations
      has emerged as a potentially vital network phenomenon mediating the steps between
      encoding and consolidation, both at a cellular and network level by promoting the
      rapid replay and reactivation of recent activity patterns. Such events facilitate
      memory formation by optimising the conditions for synaptic plasticity to occur
      between contingent neural elements. In this paper, we explore the ways in which
      SWRs and other network events can bridge the gap between spatiomnemonic
      processing at cellular/synaptic and network levels in the hippocampus.

PMID- 21961076
TI  - Local reference ranges of thyroid volume in sudanese normal subjects using
      ultrasound.
AB  - This study aimed to establish a local reference of thyroid volume in Sudanese
      normal subjects using ultrasound. A total of 103 healthy subjects were studied,
      28 (27.18%) females and 75 (72.82%) males. Thyroid volume was estimated using
      ellipsoid formula. The mean age and range of the subjects was 21.8 (19-29) years;
      the mean body mass index (BMI) was 22.3 (16.46-26.07) kg/m(2). The overall mean
      volume +/- SD volume of the thyroid gland for both lobes in all the patients
      studied was 6.44 +/- 2.44 mL. The mean volume for both lobes in females and males
      were 5.78 +/- 1.96 mL and 6.69 +/- 2.56 mL, respectively. The males' thyroid
      volume was greater than the females'. The mean volume of the right and left lobes
      of the thyroid gland in males and females were 3.38 +/- 1.37 mL and 3.09 +/- 1.24
      mL, respectively. The right thyroid lobe volume was greater than the left. The
      values obtained in this study were lower than those reported from previous
      studies.

PMID- 21961079
TI  - Pathology of breast carcinoma: diagnostic, prognostic, and therapeutic issues and
      challenges.

PMID- 21961077
TI  - Perception of speech by individuals with Parkinson's disease: a review.
AB  - A few clinical reports and empirical studies have suggested a possible deficit in
      the perception of speech in individuals with Parkinson's disease. In this paper,
      these studies are reviewed in an attempt to support clinical anecdotal
      observations by relevant empirical research findings. The combined evidence
      suggests a possible deficit in patients' perception of their own speech loudness.
      Other research studies on the perception of speech in this population were
      reviewed, in a broader scope of the perception of emotional prosody. These
      studies confirm that Parkinson's disease specifically impairs patients'
      perception of verbal emotions. However, explanations of the nature and causes of
      this perceptual deficit are still limited. Future research directions are
      suggested.

PMID- 21961078
TI  - Pathology of acute henipavirus infection in humans and animals.
AB  - Zoonoses as causes of human infections have been increasingly reported, and many
      of these are viruses that cause central nervous system infections. This paper
      focuses on the henipaviruses (family Paramyxoviridae, genus henipavirus) that
      have recently emerged to cause severe encephalitis and systemic infection in
      humans and animals in the Asia-Pacific region. The pathological features in the
      human infections comprise vasculopathy (vasculitis, endothelial multinucleated
      syncytia, thrombosis, etc.) and parenchymal cell infection in the central nervous
      system, lung, kidney, and other major organs. Most animals naturally or
      experimentally infected show more or less similar features confirming the dual
      pathogenetic mechanism of vasculopathy-associated microinfarction and direct
      extravascular parenchymal cell infection as causes of tissue injury. The most
      promising animal models include the hamster, ferret, squirrel monkey, and African
      green monkey. With increasing evidence of infection in the natural hosts, the
      pteropid bats and, hence, probable future outbreaks in many more countries, a
      greater awareness of henipavirus infection in both humans and animals is
      imperative.

PMID- 21961081
TI  - Diagnosis/Classification Criteria for Behcet's Disease.
AB  - Historical Background. The ISG criteria for Behcet's, created in 1990, have
      excellent specificity, but lack sensitivity. The International Criteria for
      Behcet's Disease (ICBD) was created in 2006, as replacement to ISG. The aim of
      this study was to compare their performance. ISG and ICBD Criteria. For ISG oral
      aphthosis is mandatory. The presence of any two of the following (genital
      aphthosis, skin lesions, eye lesions, and positive pathergy test) will
      diagnose/classify the patient as BD. For ICBD, vascular lesions were added, while
      oral aphthosis is no more mandatory. Getting 3 or more points diagnose/classify
      the patient as BD (genital aphthosis 2 points, eye lesions 2 points, and the
      remaining each one point). Performance and Comparison of ISG and ICBD. Their
      sensitivity, specificity, and accuracy (percent agreement), were tested in three
      independent cohort of patients from Far-East (China), Middle-East (Iran), and
      Europe (Germany). The sensitivity for ISG was respectively 65.4%, 78.1%, 83.7%
      and for ICBD 87%, 98.2%, and 96.5%. The specificity for ISG was 99.2%, 98.8%,
      89.5% and for ICBD 94.1%, 95.6%, and 73.7%. The accuracy for ISG was 74.2%,
      85.5%, 85.5% and for ICBD 88.9%, 97.3%, and 89.5%. Conclusion. ICBD has better
      sensitivity, and accuracy than ISG.

PMID- 21961080
TI  - Histological correlation of glandular abnormalities in cervical liquid-based
      cytology.
AB  - Conventional Papanicolaou smear method is still commonly used for cervical cancer
      screening in Japan, despite the liquid-based cytology (LBC) that has become a
      global tendency in the world recently. One of the obstacles in the way of
      popularization of this method seems to be the confusion as to diagnosis upon
      cervical glandular lesions. We performed comparison study between LBC and
      conventional Papanicolaou smear about cytological diagnosis using split-sample
      method in 4522 patients. In 13 cases analyses, which were reported with either
      AGC or adenocarcinoma by either method, LBC tends to be milder than that by
      conventional smear, however, the credibility of LBC is considered to be near to
      that of conventional smear with regard to screening for glandular abnormalities.
      These results indicate that cervical cancer screening should shift to LBC under
      the enough experience and appropriate dealing with the cytological diagnosis.

PMID- 21961082
TI  - Musculoskeletal Findings in Behcet's Disease.
AB  - Behcet's disease is a multisystem disease characterized by recurrent oral and
      genital ulcers, relapsing uveitis, mucocutaneous, articular, gastrointestinal,
      neurologic, and vascular manifestations. Rheumatologic manifestations may also
      occur in Behcet's disease, and arthritis and arthralgia are the most common
      musculoskeletal findings followed by enthesopathy, avascular necrosis, myalgia,
      and myositis. Although the main pathology of Behcet's disease has been known to
      be the underlying vasculitis, the etiology and exact pathogenesis of the disease
      are still unclear. Musculoskeletal findings of Behcet's disease, the relationship
      between Behcet's disease and spondyloarthropathy disease complex, and the status
      of bone metabolism in patients with Behcet's disease were discussed in this
      paper.

PMID- 21961083
TI  - Cardiopulmonary response to exercise testing in people with chronic stroke: a
      retrospective study.
AB  - Background and Purpose. This study investigated the cardiopulmonary response and
      safety of exercise testing at peak effort in people during the chronic stage of
      stroke recovery. Methods. This retrospective study examined data from 62
      individuals with chronic stroke (males: 32; mean (SD); age: (12.0) yr)
      participating in an exercise test. Results. Both males and females had low
      cardiorespiratory fitness levels. No significant differences were found between
      gender for peak HR (P = 0.27), or VO(2) peak (P = 0.29). Males demonstrated
      higher values for minute ventilation, tidal volume, and respiratory exchange
      ratio. No major adverse events were observed in the exercise tests conducted.
      Discussion and Conclusion. There are differences between gender that may play a
      role in exercise testing performance and should be considered when developing
      exercise programs. The low VO(2) peak of this cohort of chronic stroke survivors
      suggests the need for participation in exercise interventions.

PMID- 21961085
TI  - FPGA-Based Front-End Electronics for Positron Emission Tomography.
AB  - Modern Field Programmable Gate Arrays (FPGAs) are capable of performing complex
      discrete signal processing algorithms with clock rates above 100MHz. This
      combined with FPGA's low expense, ease of use, and selected dedicated hardware
      make them an ideal technology for a data acquisition system for positron emission
      tomography (PET) scanners. Our laboratory is producing a high-resolution, small
      animal PET scanner that utilizes FPGAs as the core of the front-end electronics.
      For this next generation scanner, functions that are typically performed in
      dedicated circuits, or offline, are being migrated to the FPGA. This will not
      only simplify the electronics, but the features of modern FPGAs can be utilizes
      to add significant signal processing power to produce higher resolution images.
      In this paper two such processes, sub-clock rate pulse timing and event
      localization, will be discussed in detail. We show that timing performed in the
      FPGA can achieve a resolution that is suitable for small-animal scanners, and
      will outperform the analog version given a low enough sampling period for the
      ADC. We will also show that the position of events in the scanner can be
      determined in real time using a statistical positioning based algorithm.

PMID- 21961086
TI  - What has the optimistic bias got to do with the need to differentiate fatty liver
      from nonalcoholic steatohepatitis?

PMID- 21961084
TI  - Neuron-Microglia Dialogue and Hippocampal Neurogenesis in the Aged Brain.
AB  - Age-related changes in innate immune function and glial-neuronal communication
      are early and critical events in brain aging and neurodegenerative disease, and
      lead to a chronic increase in oxidative stress and inflammation, which initiates
      neuronal dysfunction and reduced synaptic plasticity, and ultimately disruption
      in learning and memory in the aged brain. Several lines of evidence suggest a
      correlation between adult neurogenesis and learning. It has been proposed that a
      decline in hippocampal neurogenesis contributes to a physiologic decline in brain
      function. Recently, new and important insights relating to the production of new
      neurons affecting hippocampal-dependent memory ability have been provided. A
      multitude of factors have been shown to regulate the production of new neurons in
      the adult hippocampus, many of which change as a result of aging. Yet, the
      potential importance of neurogenesis in some affective and cognitive behaviors,
      as well as endogenous tissue repair mechanisms, makes further investigation of
      neurogenic regulators warranted. We have recent evidence that key regulators of
      communication between neurons and microglia are disrupted in the aged brain and
      may be one of the factors that precedes and initiates the observed increase in
      chronic inflammatory state. In this review the role of dysfunction in these
      neuronal-glial communication regulators underlying age-related impairments in
      cognition and hippocampal neurogenesis will be discussed. An understanding of
      these mechanisms will lead to the development of preventive or protective
      therapies.

PMID- 21961087
TI  - Pseudomelanosis coli and adenomatous polyps.

PMID- 21961088
TI  - Successful treatment of a bleeding duodenal varix by endoscopic band ligation.

PMID- 21961090
TI  - Quality of life in Coeliac Disease is determined by perceived degree of
      difficulty adhering to a gluten-free diet, not the level of dietary adherence
      ultimately achieved.
AB  - BACKGROUND: Coeliac Disease (CD) is an increasingly common autoimmune condition,
      the treatment of which is a gluten-free diet (GFD). Previous studies fail to
      reach consensus of the impact this restrictive diet has on an individual's
      quality of life (QoL). Furthermore, how patient characteristics, such as
      demographic and educational background, may predict GFD adherence is poorly
      understood. We aimed to assess which factors had an impact on Qol in patients
      with CD. METHODS: Case-control postal survey (n=573). Biopsy-proven CD patients
      (n=225; mean disease duration 8yrs; range 0.5-52yrs; male 26%) and age and sex
      matched controls (n=348; male 36%) completed The Short-Form 36-Item (SF-36) QoL
      measure, The Hospital Anxiety & Depression Scale (HADS), GFD assessment, and
      demographic questionnaire. RESULTS: We found a high proportion of GFD adherence:
      'Full Adherence' 65%, 'Partial Adherence' 31%, 'None Adherence' 4%, accompanied
      however, by 80% of patients reporting difficulty adhering to the GFD:
      'Impossible' 5%, 'Mostly difficult' 14%, 'Sometimes difficult' 61%, 'No
      difficulty' 20%. Negligible differences in QoL scores were observed when
      comparing full versus partial/none GFD patients (P=>0.05), however, stepwise
      reductions in QoL and increasing likelihood of anxiety/depression were found in
      association with increasing degree of difficulty adhering to the GFD (P=<0.0001).
      Demographic assessment suggests that an affluent background and a university
      education promote greater GFD adherence. CONCLUSIONS: Most coeliac patients
      adhere to a GFD but encounter difficulty doing so (potentially influenced by
      social and educational background). The degree of GFD difficulty is associated
      with reductions in patient wellbeing and psychological distress that the
      dietician is critically placed to address.

PMID- 21961089
TI  - Primary clarithromycin resistance in Helicobacter pylori: the Multicentric
      Italian Clarithromycin Resistance Observational (MICRO) study.
AB  - BACKGROUND: Primary clarithromycin resistance markedly reduces Helicobacter
      pylori eradication rate following standard therapies. Prevalence of primary
      clarithromycin resistance in H. pylori is increasing, and three point mutations
      are mainly involved. AIM. To assess both the prevalence of primary clarithromycin
      resistance in Italy, and the distribution of the involved point mutations.
      METHODS: Primary clarithromycin resistance was assessed by TaqMan real-time
      polymerase chain reaction on antral biopsies of 253 consecutive, H. pylori
      infected patients enrolled in 13 Italian centres between January and September
      2010. RESULTS: Primary clarithromycin resistance was detected in 25 (9.9%)
      patients, with prevalence values widely ranging from 0 to 25%. Clarithromycin
      resistance rate was higher in female as compared to male patients (13.4% vs.
      5.3%, p=0.03), and it tended to be higher in non-ulcer dyspepsia than in peptic
      ulcer patients (10.6% vs. 6.9%, p=0.5), female patients with non-ulcer dyspepsia
      showing the highest value (15.4%). The A2143G point mutation was detected in 13
      (52.0%) patients, the A2142G in 9 (34.6%), whilst a double point mutation (A2143G
      plus A2142G) in 3 (11.6%) cases. CONCLUSIONS: Primary clarithromycin resistance
      is highly variable in different Italian geographic areas. High resistance rates
      were observed in female and in dyspeptic patients. Among the three point
      mutations of clarithromycin resistance, the A2143G remains the most frequently
      observed.

PMID- 21961091
TI  - A pharmacogenetics study of TPMT and ITPA genes detects a relationship with side
      effects and clinical response in patients with inflammatory bowel disease
      receiving Azathioprine.
AB  - BACKGROUND AND AIMS: Pharmacogenetic studies in inflammatory bowel diseases (IBD)
      are mainly focused on genes involved in the metabolism of Azathioprine (AZA). Use
      of AZA is limited by its toxicity, which occurs in 20-30% of patients. Variants
      in the Thiopurine S-methyltransferase (TPMT) and Inosine triphosphate
      pyrophosphatase (ITPA) genes have been associated with AZA toxicity, but also can
      contribute to the lack of response. The aims of this study were to determine the
      contribution of TPMT and ITPA variants in the development of AZA-related toxicity
      and response. METHODS: Variants associated with the decrease of enzyme activity
      in TPMT and ITPA genes were genotyped with the Snapshot system in 232 IBD
      patients treated with AZA, and correlated with the clinical response and
      development of adverse drug reactions in a retrospective case-control study.
      RESULTS: Genotypic analysis showed that there is a statistical significance
      between c.94C > A variant on ITPA gene with non response to AZA treatment
      (p=0.005) and arthralgia (OR 8.2353; 95%CI 1.752-38.87, p=0.0041), as well as
      between mutant TPMT alleles and myelosuppression (OR 7.5; 95%CI 1.4456-38.91,
      p=0.0304). CONCLUSIONS: There is a positive correlation between c.94C > A variant
      on ITPA with clinical response. Mutant alleles on TPMT and the variant c.94C > A
      on ITPA gene predict side effects induced by AZA in our population
      (myelosuppression and arthralgia).

PMID- 21961092
TI  - Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) as candidates for
      tumor markers in patients with pancreatic cancer.
AB  - BACKGROUND: Various alcohol dehydrogenase (ADH) isoenzymes and aldehyde
      dehydrogenase (ALDH) exist in the pancreas. Moreover, ADH and ALDH are present in
      pancreatic cancer cells. The activity of ADH class III isoenzymes is
      significantly higher in cancerous than in healthy tissues. The expression of
      these enzymes in cancer cells is reflected by increased enzyme activity in the
      sera and thus could be helpful for diagnosing pancreatic cancer. The aim of this
      study was to investigate the potential role of ADH and ALDH as tumor markers for
      pancreatic carcinoma. METHODS: Serum samples were taken from 165 patients with
      pancreatic cancer and 166 healthy controls. Total ADH activity and class III and
      IV isoenzymes were measured by photometric and ALDH activity, ADH I and II by the
      fluorometric method. RESULTS: There was a significant increase in the activity of
      ADH III isoenzyme (14.03 mU/l vs 11.45 mU/l; p < 0.001) and total ADH activity in
      the sera of pancreatic cancer patients compared to the control. The diagnostic
      sensitivity for ADH III was 70%, specificity 76%, positive and negative
      predictive values were 79% and 71% respectively. Area under ROC curve for ADH III
      was 0.64. CONCLUSION: The results suggest a potential role for ADH III as a
      marker of pancreatic cancer.

PMID- 21961093
TI  - Molecular epidemiology of hepatitis C virus strains from Romania.
AB  - BACKGROUND AND AIMS: A high seroprevalence of Hepatitis C Virus (HCV) infection
      has been reported in Romania, with limited data on the viral subtypes'
      distribution. In order to detect any changes in the genetic composition of the
      epidemic, a survey on the recent profile of circulating HCV genotypes was
      conducted. METHODS: 241 hepatitis C infected patients with active viral
      replication diagnosed between September 2004 - October 2008 were included in a
      retrospective study. Genotyping using commercial Line Probe Assay (Innogenetics)
      was confirmed by sequencing of Core PCR products followed by phylogenetic
      analysis. RESULTS: HCV subtype 1b was found in 92.6% of the samples, subtype 1a
      in 5.4 % of the samples, subtype 4a in 1.2%, and subtype 3a in 0.8% of the
      samples. Chronic hepatitis C infections with subtype 1b were found in women aged
      40-60 years old with a history of blood transfusions received during
      surgical/obstetrical interventions. No geographical clustering was evident for
      HCV 1b sequences. The new emerging non-1b genotypes were detected mainly in
      younger patients with a history of intravenous drug use. The genetic distances
      among the HCV 1a strains are very homogeneous and small, with a high sequence
      identity with other European strains, suggesting the recent entrance of this
      subtype in Romania from singular or limited sources of infection. CONCLUSION: The
      introduction of new HCV genotypes in Romania stimulates a continuous
      epidemiological surveillance, suggesting shifts in the transmission pathways and
      risk factors, with the possible emergence of recombinant strains in patients with
      multiple infections.

PMID- 21961094
TI  - Tacrolimus may induce the production of nucleolar anti-nuclear antibody in liver
      transplant patients.
AB  - BACKGROUND AND AIMS: Immunosuppressive drugs have been used to prevent graft
      rejection in most allo-liver recipients and the immune state of these patients
      differs greatly before and after transplant operation. This study aims at
      evaluating the immune state of liver transplant patients treated with tacrolimus
      by investigating the production of anti-nuclear antibodies (ANA). METHODS: A
      hundred and eighty-eight serum samples from 94 allo-liver recipients treated with
      tacrolimus and from 94 patients with matched liver diseases were tested for ANA
      by indirect immunofluorescence assay with HEp-2 cells as substrate. RESULTS: ANA
      were detected as positive in 20.2% of the liver transplant patients treated with
      tacrolimus, and in 12.8% of disease-matched control patients, but this difference
      was not statistically significant (P=0.17). However, the frequency of nucleolar
      ANA pattern in ANA-positive cases was significantly higher in the liver
      transplant patients (63.2%) than in the control group (16.7%) (P=0.01).
      CONCLUSION: Tacrolimus may contribute to producing nucleolar ANA in liver
      transplant patients. The autoimmune disease susceptibility of allo-liver
      recipients treated with tacrolimus requires further studying.

PMID- 21961095
TI  - Optimized tandem amiRNA mediates stronger inhibitory effects on hepatitis B virus
      infection.
AB  - BACKGROUND AND AIMS: RNA interference (RNAi) has emerged as a potential new
      approach against hepatitis B virus (HBV) infection but unfortunately it also
      selects resistant virus mutants. In this study we combined the advantages of
      artificial micro RNAs (amiRNAs) reported previously with the purpose of
      constructing a more practical amiRNA with high inhibition effects against HBV.
      METHOD: Aiming at conserved sites, we constructed singular-sequence vectors
      amiRNA-HBV1, amiRNA-HBV2, amiRNA-HBV3 and amiRNA-HBV4. We chose the two sequences
      of high efficiency, then built the tandem-sequence vector amiRNA-HBV3-HBV4. These
      vectors were transfected into HepG2.2.15 transiently. The secreted HBV surface
      antigen (HBsAg) and HBV 'e' antigen (HBeAg) were measured with a chemiluminescent
      microparticle immunoassay, and intracellular and extracellular HBV DNA was
      quantified by real-time PCR. RESULTS: Our results demonstrated that amiRNA-HBV1,
      amiRNA-HBV2, amiRNA-HBV3, and amiRNA-HBV4 achieved a maximum inhibition of HBV
      mRNA expression of 29.3%, 14.9%, 61.2%, and 75.6%, respectively, while the tandem
      amiRNA-HBV3-HBV4 vector led to an inhibition of 87.2%. CONCLUSION: Taken
      together, our data suggest that vector-based multiple artificial microRNAs are a
      promising therapeutic approach for chronic HBV infection.

PMID- 21961096
TI  - Appropriateness of the indication for colonoscopy:  systematic review and meta
      analysis.
AB  - BACKGROUND AND AIMS: Application of appropriate indications for colonoscopy (OC)
      should conserve limited endoscopic resources. To perform a systematic review and
      meta-analysis to assess the accuracy of ASGE and EPAGE guidelines in selecting
      patients referred for OC, relative to the detection of neoplastic and non
      neoplastic relevant endoscopic findings. METHODS: Studies comparing the
      appropriateness of OC indication according to ASGE or EPAGE guidelines and the
      detection of cancer, adenomas, and benign relevant endoscopic findings were
      identified by searching MEDLINE (1982 - June 2009). Predefined outputs of the
      meta-analysis were sensitivity, specificity, positive and negative likelihood
      ratios (LR+, LR-), and the diagnostic odds ratio (DOR). RESULTS: We included
      twelve cohort studies comprising 14,160 patients; 10,056 OC indications were
      categorized as appropriate, and 3,522 (26%) as inappropriate. For cancer
      detection, the weighted sensitivity, specificity, LR+, LR- and DOR were 89% (95%
      CI, 82-93%), 26% (95% CI, 21-31%), 1.2 (95% CI, 1.1-1.3), 0.45 (95% CI, 03-0.7),
      and 3 (95% CI, 1-5), respectively. For adenomas, the adjusted sensitivity,
      specificity, LR+, LR- and DOR were 85% (95% CI, 77-91%), 27% (95% CI, 22-32%),
      1.14 (95% CI, 1-1.2), 0.6 (95% CI, 0.4-0.9), and 1.9 (95% CI, 1.2, 2.9), being
      for relevant findings equal to 89% (95% CI, 82-93%), 26% (95% CI, 21-31%), 1.16
      (95% CI, 1-1.3), 0.44 (95% CI, 0.25-0.8), and 2.6 (95% CI, 1.2-5.6). CONCLUSIONS:
      Appropriateness guidelines appeared to have a suboptimal sensitivity and a poor
      specificity for colorectal cancer, being also characterized by a similar accuracy
      for the diagnosis of benign relevant endoscopic findings. Better strategies are 
      required to select patients with significant pathology for OC.

PMID- 21961097
TI  - Plasma or serum TIMP-1 is a predictor of survival outcomes in colorectal cancer:
      a meta-analysis.
AB  - BACKGROUND AND AIMS: Tissue inhibitor of metalloproteinase-1 (TIMP-1) is a small
      secretory glycoprotein with anti-apoptosis and anti-matrix metalloproteinase
      activity. There have been some discordant data regarding the value of TIMP-1 as a
      prognostic factor in colorectal cancer (CRC) patients. To address this
      controversy, we conducted a meta-analysis for the relationship between TIMP-1
      levels and overall survival in CRC. METHODS: We selected the relevant published
      studies using citation databases including PubMed, Science Citation Index, and
      Conference Papers Index. The effect sizes of TIMP-1 on the patient's overall
      survival and TNM stages were calculated by hazard ratio (HR) or odds ratio (OR),
      respectively. The effect sizes were combined using a random-effects model.
      RESULTS: Survival outcomes between high and low plasma or serum TIMP-1 levels
      were compared by uni- and multivariate analyses involving 1,477 and 1,359 CRC
      patients, respectively. CRC patients with high plasma or serum TIMP-1 levels
      showed poor survival rates compared to patients with low plasma or serum TIMP-1
      in the uni- and multivariate analyses (HR, 2.2 and 2.1; P < 0.001). In addition,
      high TIMP-1 expression in colon cancer tissues was significantly associated with
      worse survival outcomes in 438 CRC patients (HR = 1.4; P = 0.017). CONCLUSION:
      Plasma or serum TIMP-1 levels predict survival outcomes of CRC patients.

PMID- 21961098
TI  - Response to standard of care antiviral treatment in patients with HCV liver
      cirrhosis - a systematic review.
AB  - BACKGROUND: Patients with HCV liver cirrhosis are a category difficult to treat.
      The aim of this study was to establish the sustained virological response (SVR)
      rates in HCV patients with liver cirrhosis treated with standard of care therapy
      (Pegylated Interferon and Ribavirin for 48 weeks in genotypes 1 and 4 and 24
      weeks in genotypes 2 and 3). METHODS: Searching the PubMed, Medline, Lilacs,
      Scopus, Ovid and Medscape databases we identified all the articles published
      until February 2011 that included only HCV cirrhotic patients. These studies
      evaluated the SVR after standard of care treatment: Pegylated Interferon alpha 2a
      (doses ranging between 135-180 ug/week) or Pegylated Interferon alpha 2b (1 or
      1.5 ug/kg/week) and Ribavirin (doses ranging between 800-1200 mg/day). We used
      the following key words: HCV, liver cirrhosis, sustained virological response
      (SVR). RESULTS: The overall SVR rate was 33.3% (95%CI-confidence interval=30.6
      36.2%). SVR was significantly higher in patients with genotypes 2 and 3 (422
      patients) as compared to those with genotypes 1 and 4 (692 patients): 55.4%
      (95%CI=50.7-60.1) versus 21.7% (95%CI=18.7-25), p < 0.0001. CONCLUSION: The
      overall SVR rate in cirrhotic patients treated with standard of care therapy is
      33.3%, but lower in cases affected by genotypes 1 and 4 (21.6%) which makes them
      a priority regarding the development of more potent drugs for effective
      treatment.

PMID- 21961101
TI  - Computed virtual chromoendoscopy - enhanced videocapsule endoscopy is of
      potential benefit in gastric antral vascular ectasia syndrome refractory to
      endoscopic treatment.
AB  - Gastric antral vascular ectasia (GAVE) syndrome represents a rare cause of
      gastrointestinal bleeding. More extensive small-bowel involvement must be
      excluded in those patients with GAVE syndrome in whom aggressive endoscopic
      treatment of antral lesions results in lack of control of digestive bleeding, and
      for this subset of patients videocapsule endoscopy examination should be
      considered. However, since the dim angioectatic lesions, even if located in the
      gastric antrum, might be difficult to accurately outline with standard endoscopy,
      virtual chromoendoscopy techniques have been employed to aid in their detection,
      and the presented case illustrates how Fujinon intelligent color-enhancement
      (FICE) technology implemented in videocapsule endoscopy clearly emphasizes the
      vascular morphology and delineation of antral angioectasias, allowing better
      targeted endoscopic treatment and improving patient outcome.

PMID- 21961099
TI  - Helicobacter pylori in developing countries. World Gastroenterology Organisation
      Global Guideline.

PMID- 21961102
TI  - The association between Helicobacter Pylori chronic gastritis, psychological
      trauma and somatization disorder. A case report.
AB  - Helicobacter Pylori is considered to be the agent responsible for peptic ulcers
      and gastritis, and its eradication represents a main objective in the treatment
      of digestive diseases. We present the case report of a female patient diagnosed
      with chronic Helicobacter Pylori infection, where symptoms manifested after the
      patient was raped. In the context of psychological trauma, digestive
      manifestations such as ulcer and gastritis were identified, greatly exacerbated
      as compared with the endoscopic and histological aspect of the gastric mucosa.
      The patient simultaneously developed a complex psychiatric pathology. The
      association between Helicobacter Pylori chronic gastritis, somatization and
      trauma is discussed.

PMID- 21961103
TI  - Autoimmune pancreatitis with response to chemoradiation therapy.
AB  - Autoimmune pancreatitis (AIP) sometimes mimics pancreatic cancer, and is rarely
      resected under this misdiagnosis. However, there is no report in the literature
      regarding a case of AIP, which was misdiagnosed as an inoperative stage of
      pancreatic cancer and which received systemic chemotherapy with or without
      radiation. We report a 59-year-old man with a mass-forming lesion at the
      pancreatic head involving the common hepatic artery and portal vein, initially
      diagnosed as locally advanced pancreatic cancer and treated with chemoradiation
      therapy. After a month of continuous infusion of low dose 5-fluorouracil with
      concurrent local radiation (50.4 Gy), the pancreatic lesion diminished in size.
      However, the pancreatic body gradually enlarged and a capsule-like limb appeared
      in the following year. Serological markers and endoscopic retrograde
      cholangiopancreatography were compatible with those of AIP. No neoplastic tissue
      was identified on the fine needle aspiration biopsy of the pancreas. The
      pancreatic lesion responded well to steroid therapy and the patient remained in
      remission for one year after the withdrawal of steroids. Similar to pancreatic
      cancer, this current case of AIP responded to chemoradiation. Both serological
      and histological examinations were essential for images equivocal for either
      locally advanced pancreatic cancer or AIP.

PMID- 21961104
TI  - A case report of abdominal splenosis - a practical mini-review for a
      gastroenterologist.
AB  - Splenosis is a benign condition caused by ectopic autotransplantation of splenic
      tissues after splenic trauma or surgery. It is usually diagnosed accidentally.
      However, occasionally splenosis poses a significant diagnostic dilemma,
      especially when this condition presents as a metastatic malignant disease on
      abdominal imaging. This is the case report of a 54-year-old woman, who underwent
      post-traumatic splenectomy at the age of 12 years. The physical examination of
      this patient complaining of epigastric and low back pain, except for
      postoperative abdominal scar, as well as laboratory tests were normal.
      Esophagogastroduodenoscopy showed chronic gastritis. Abdominal ultrasound
      revealed no spleen, enlarged lymph nodes in the right retroperitoneum and a focal
      lesion in the uterus. In addition, the CT scan disclosed enlarged left hepatic
      lobe, numerous oval tumors between intestinal loops, in the caecal region, under
      the diaphragm and abdominal wall, periaortic enlarged lymph nodes and an
      osteolytic lesion in the first lumbar vertebra, suggesting disseminated malignant
      disease. The exploratory laparotomy showed multiple abdominal nodules, a tumor of
      the ileum, the greater omentum and the uterus. Except for the last one
      (leiomyoma), all excised tumors proved to have histological structure typical for
      the spleen and, finally, abdominal splenosis was diagnosed. Splenosis should be
      considered when a differential diagnosis of tumor-like lesions disclosed on
      abdominal imaging occurs in a patient with a splenic injury in the past.

PMID- 21961106
TI  - Pancreatic tumor and Gitelman syndrome.

PMID- 21961105
TI  - Duodopa infusion treatment: a point of view from the gastroenterologist.
AB  - In patients with advanced Parkinson's disease, the continuous delivery to the
      small intestine via a jejunal tube of levodopa/carbidopa, formulated as a gel
      suspension (Duodopa) represents a new treatment method. The continuous release
      results in less variability in levodopa concentrations and fewer motor
      fluctuations and dyskinesias than with oral administration. The method which
      requires a very good collaboration between the neurologist and the
      gastroenterologist is used with increasing frequency in selected centres
      especially in severe patients. First, a classic PEG gastrostomy kit is placed
      under propofol sedation. This allows the passage of a pig tail catheter which is
      deployed in the jejunum and it is attached to a portable pump via a special
      tubing system. We present our experience of seven cases (5 males, mean age 60
      years) with a follow up of one year. One patient died due to respiratory failure
      and aspiration pneumonia probably related to the endoscopic procedure. At one
      year, all patients agreed that the neurological benefit offsets the procedure
      related problems and the technical issues related to the enteral infusion system.

PMID- 21961107
TI  - Hepatic arteriovenous malformation with hyperammonemia in Rendu-Osler-Weber
      syndrome.

PMID- 21961108
TI  - Unexplained jaundice after squirrel bite. It's not what you look at that matters,
      it's what you see (H. D. Thoreanu).

PMID- 21961109
TI  - Asymmetric logistic peak as a suitable function for the resolution of highly
      asymmetric voltammograms in non-bilinear systems.
AB  - The asymmetric logistic peak is tested as a new function for the parametric
      signal fitting (PSF) of highly asymmetric electrochemical signals in non-bilinear
      datasets, such as those obtained in linear sweep voltammetry (LSV) or in the
      presence of irreversible electrochemical processes. This new multivariate curve
      resolution strategy (PSF-ALPA) is successfully applied to LS voltammograms
      measured for the Cd(II)-glutathione system with a hanging mercury drop electrode,
      where Cd(II) is reversibly reduced, and to differential pulse voltammograms (DPV)
      measured at a glassy carbon electrode, where Cd(II) reduction becomes
      irreversible. Matrix augmentation by using LS voltammograms measured at different
      scan rates provides good results and encourages the development of ALPA
      methodology for third order data.

PMID- 21961110
TI  - Evaluation of the potential of surface enhancement Raman spectroscopy for
      detection of tricyclic psychotropic drugs. Case studies on imipramine and its
      metabolite.
AB  - The potential use of surface Raman enhanced spectroscopy (SERS) for confirmatory
      identification and the semi-quantitative analysis of selected tricyclic
      antidepressants (TCAs) is examined utilizing a conventional silver colloid. Raman
      and SERS spectra of aqueous solutions of imipramine (Imi) and its metabolite,
      desipramine (Des), were recorded as the function of concentration using NIR
      excitation. A good linear correlation is observed for the dependence of the SERS
      signal at 684 cm(-1) (R(2) = 0.9997) on Imi concentration over the range of 0.75
      7.5 MUM. The limit of detection of imipramine in the silver colloidal solution is
      0.98 MUM. SERS spectra of Imi and Des were also recorded for blood plasma samples
      without prior purification as well as after the use of standard solid phase
      extraction. All spectra show the characteristic spectral profile of the molecules
      and moreover, stronger signal enhancement is observed for Imi in the "raw"
      samples as opposed to Imi extracted from a biological matrix.

PMID- 21961111
TI  - In situ encapsulation of laccase in nanofibers by electrospinning for development
      of enzyme biosensors for chlorophenol monitoring.
AB  - A biosensor based on Trametes versicolor laccase (Lac) was developed for the
      determination of phenolic compounds. The biosensor was prepared by in situ
      electrospinning of a mixture of polyvinyl alcohol (PVA), Lac, PEO-PPO-PEO (F108)
      and gold nanoparticles (Au NPs), where F108 was used as an enzyme stabilizing
      additive and Au NPs was used to enhance the conductivity of the biosensor. Laser
      confocal scanning microscopy and electrochemical impedance spectroscopy proved
      that the enzyme was successfully encapsulated into the electrospun nanofibers.
      Under the optimal conditions, the lowest detection limit was found to be 0.04 MUM
      (S/N = 3) for 2,4-DCP and the highest detection limit was found to be 12.10 MUM
      for 4-CP. The sensitivity of the biosensor obtained in the linear range for
      chlorophenols followed the sequence 2,4-dichlorophenol (2,4-DCP) > 2,4,6
      trichlorophenol (2,4,6-TCP) > 4-chlorophenol (4-CP). The sensing performance for
      chlorophenols was attributed to the suitable electrochemical interface of
      PVA/F108/Au NPs/Lac, resulting from biocompatibility, a high surface area-to
      volume ratio (10.42 m(2) g(-1)) and superior mechanical properties of the
      electrospun nanofibers. The biosensor exhibited good repeatabilities of 7.6%,
      2.8% and 9.0% (R.S.D.) and reproducibilities of 14.9%, 10.4% and 13.7% (R.S.D.)
      for 4-CP, 2,4-DCP and 2,4,6-TCP, respectively. Lac retained 65.8% of its initial
      activity after a 30-day storage period.

PMID- 21961112
TI  - Inorganic-organic chain assemblies as lamellar nanoreactors for growing one
      dimensional Cu(OH)2 and CuO nanostructures.
AB  - One-dimensional Cu(OH)(2) or CuO nanostructures were fabricated using inorganic
      organic chain assemblies, Cu(C(n)H(2n+1)X)(2).nH(2)O (X = CO(2), SO(4)) as a
      lamellar nanoreactor, along with NaOH treatment. The shapes and aspect ratios of
      the Cu(OH)(2) or CuO nanostructures could be varied by adjusting the
      hydrophobicity of the lamellar nanoreactors.

PMID- 21961113
TI  - Efficient RNA synthesis by in vitro transcription of a triazole-modified DNA
      template.
AB  - A DNA strand containing a triazole phosphodiester mimic is an efficient template
      for in vitro transcription. This is the first demonstration of transcription
      through a heavily modified DNA backbone linkage and it suggests that click
      ligated DNA could be useful for the direct synthesis of biologically active RNA
      and proteins.

PMID- 21961122
TI  - The healing power of art: is it just for patients?
AB  - To be a caring professional one must learn to care for oneself. This article is
      an exemplar of one nurse's discovery of the use of music to cope with stress and
      grief.

PMID- 21961123
TI  - Designing the invisible architecture of your hospital.
AB  - Before building or remodeling a hospital, architects develop a complete set of
      blueprints. That same sort of detailed attention should be given to the
      "invisible architecture" of core values, corporate culture, and emotional
      attitude because this has a much greater impact on the patient and employee
      experience than do the bricks and mortar.

PMID- 21961124
TI  - What floats a float nurse's boat?
AB  - Few studies have examined the personality traits of nurses, and none identified
      the personality traits of float pool nurses. Float pool nurses have specific
      personality traits that differ from unit-based nurses. Independence, Tough
      Mindedness, Rule Consciousness, Social Boldness, Openness to Change, and Tension
      were six personality factors that were found to be statistically significantly
      different. As hospitals implement float pools or resource teams to meet staffing
      needs, gleaning insight into the specific personality traits of these individuals
      could assist in nurse recruitment and retention.

PMID- 21961125
TI  - Implementing a professional nursing practice philosophy and model: using
      affective methods to address resistance.
AB  - The desire of community hospitals to build more professionalism into nursing
      practice through the implementation of a practice philosophy and model can be
      driven by several factors, including practice needs, consistency, and/or a Magnet
      Recognition journey. The development team for this institution provided 30 2-hour
      sessions on professional practice to nurses on all shifts. This training was
      mandatory, with typical resistance for such programs. The rollout strategy wove
      cognitive and affective teaching methods that integrated head and heart, with
      very positive outcomes identified in postprogram evaluations.

PMID- 21961126
TI  - Creating a team that thrives: an annotated conversation with Marlene Williamson,
      MSN, RN, NE-BC. Interview by Barbara Balik.
AB  - How do successful leaders do that? In this interview with Marlene Williamson,
      director of In-patient Nursing Services at Winchester Hospital in Winchester, MA,
      she describes the leadership behaviors that created a float team that thrives,
      provides highly valued care, continually improves their individual performance,
      and usually has a waiting list of internal applicants. Barbara Balik's analysis
      of Marlene Williamson's comments are in indented paragraphs.

PMID- 21961127
TI  - The intersection of experience and ideals.

PMID- 21961136
TI  - Treatment of type IV thoracoabdominal aneurysms--open, hybrid technique with
      debranching or fenestrated stent-graft repair.

PMID- 21961137
TI  - On the occasion of the JEM 60th anniversary issue.

PMID- 21961138
TI  - Professor Toshisada Nishida (1941-2011).

PMID- 21961139
TI  - Professor Toshisada Nishida, a pioneer and a leading scientist in primatology.

PMID- 21961140
TI  - Lack of increase in the serum thyroid-stimulating hormone level after
      intramuscular administration of recombinant human thyroid-stimulating hormone
      doses in a morbidly obese patient.

PMID- 21961141
TI  - Rapid weight loss and decrease in hemoglobin A1c after treatment with topiramate
      in a patient with status epilepticus.

PMID- 21961142
TI  - Three-dimensional ultrasound images and fine-needle aspiration biopsy of a
      thyroid nodule.

PMID- 21961154
TI  - [In Process Citation].

PMID- 21961156
TI  - Lead poisoning in cattle associated with car batteries and sump oil.

PMID- 21961161
TI  - Retraction. Hypoadiponectinemia is caused by chronic blockade of nitric oxide
      synthesis in rats, Metabolism 2005;54(4):482-487.

PMID- 21961163
TI  - New chapters in the story of PD.

PMID- 21961162
TI  - Regulation of cholesterol metabolism: the work of Robert D. Simoni. 1988, 1999.

PMID- 21961164
TI  - Abstracts of the AABB Annual Meeting and CTTXPO. San Diego, California, USA.
      October 22-25, 2011.

PMID- 21961165
TI  - EACPR clinical methods training course.

PMID- 21961168
TI  - Refuting the 'paradox of sports'.

PMID- 21961169
TI  - Cardiologists and medical devices: time to get involved.

PMID- 21961170
TI  - Diary of the "mad" med-lab techs. Rapid testing methods in microbiology.

PMID- 21961171
TI  - Mello's StatSpin brings LEAN processing to labs.

PMID- 21961173
TI  - MicroRNA miR-133 represses HERG K+ channel expression contributing to QT
      prolongation in diabetic hearts.

PMID- 21961174
TI  - Down-regulation of miR-1/miR-133 contributes to re-expression of pacemaker
      channel genes HCN2 and HCN4 in hypertrophic heart.

PMID- 21961175
TI  - Bibliography. Cancer in AIDS. Current world literature.

PMID- 21961176
TI  - Bibliography. Gynecologic cancer. Current world literature.

PMID- 21961177
TI  - Microbiology by numbers.

PMID- 21961178
TI  - Timeline of the ancient mariners.

PMID- 21961180
TI  - CO2 and formate complexes of phosphine/borane frustrated Lewis pairs.
AB  - The reaction of a solution of B(C6F4H)3 and either iPr3P or tBu3P with CO2
      afforded the species R3P(CO2)B(C6F4H)3 (R=iPr (1), tBu (2)). In a similar fashion
      the boranes, RB(C6F5)2 (R=hexyl, cyclohexyl (Cy), norbornyl), ClB(C6F5)2, or
      PhB(C6F5)2 were combined with tBu3P and CO2 to give the species
      tBu3P(CO2)BR(C6F5)2 (R=hexyl (3), Cy (4), norbornyl (5), Cl (6), Ph (7)).
      Similarly, the compounds [tBu3PH][RBH(C6F5)2] (R= hexyl (8), Cy (9), norbornyl
      (10)) were prepared by reaction of the precursor frustrated Lewis pair (FLP) with
      H2. Subsequent reactions of 9 and 10 with CO2 afforded the species
      [((C6F5)2BR)2(MU-HCO2)][tBu3PH] (R= Cy (11), norbornyl (12)). In related
      chemistry, combinations of the boranes RBG(C6F5)2 (R=hexyl, Cy, norbornyl) with
      tBu3P treated with an equivalent of formic acid gave [(C6F5)2BR(HCO2)][tBu3PH]
      (R=hexyl (13), Cy (14), norbornyl (15)). Subsequent addition of an additional
      equivalent of borane provides a second synthetic route to 11 and 12.
      Crystallographic studies of compounds 2-6 and 8-14 are reported and discussed.
      Further understanding of the FLP complexation and activation of CO2 is provided
      by computational studies.

PMID- 21961182
TI  - The doctorate of nursing practice: elaboration of contributions and roles.

PMID- 21961181
TI  - The clinical impact and molecular biology of del(17p) in multiple myeloma treated
      with conventional or thalidomide-based therapy.
AB  - Hemizygous deletion of 17p (del(17p)) has been identified as a variable
      associated with poor prognosis in myeloma, although its impact in the context of
      thalidomide therapy is not well described. The clinical outcome of 85 myeloma
      patients with del(17p) treated in a clinical trial incorporating both
      conventional and thalidomide-based induction therapies was examined. The clinical
      impact of deletion, low expression, and mutation of TP53 was also determined.
      Patients with del(17p) did not have inferior response rates compared to patients
      without del(17p), but, despite this, del(17p) was associated with impaired
      overall survival (OS) (median OS 26.6 vs. 48.5 months, P < 0.001). Within the
      del(17p) group, thalidomide induction therapy was associated with improved
      response rates compared to conventional therapy, but there was no impact on OS.
      Thalidomide maintenance was associated with impaired OS, although our analysis
      suggests that this effect may have been due to confounding variables. A minimally
      deleted region on 17p13.1 involving 17 genes was identified, of which only TP53
      and SAT2 were underexpressed. TP53 was mutated in <1% in patients without
      del(17p) and in 27% of patients with del(17p). The higher TP53 mutation rate in
      samples with del(17p) suggests a role for TP53 in these clinical outcomes. In
      conclusion, del(17p) defined a patient group associated with short survival in
      myeloma, and although thalidomide induction therapy was associated with improved
      response rates, it did not impact OS, suggesting that alternative therapeutic
      strategies are required for this group.

PMID- 21961183
TI  - Horror and hope: (re)presenting militarised children in global North-South
      relations.
AB  - This article examines the (re)presentations of militarised children in
      contemporary global politics. In particular, it looks at the iconic image of the
      21st century's child soldier, the subject of which is constructed as a menacing
      yet pitiable product of the so-called new wars of the global South. Yet this
      familiar image is a small, one-dimensional and selective (re)presentation of the
      issues facing children who are associated with conflict and militarism. In this
      sense it is a problematic focal point for analysing the insecurity and human
      rights of children in and around conflict. Instead, this article argues that the
      image of the child soldier asserts an important influence in its effect upon
      global North-South relations. It demonstrates how the image of the child soldier
      can assist in constructing knowledge about the global South, and the global
      North's obligations to it, either through programmes of humanitarianism, or
      through war.

PMID- 21961184
TI  - Reintegrating young combatants: do child-centred approaches leave children-and
      adults-behind?
AB  - This article uses recent experience in Angola to demonstrate that young fighters
      were not adequately or effectively assisted after war ended in 2002. The
      government's framework excluded children from accessing formal disarmament,
      demobilisation and reintegration (DDR) programmes, and its subsequent attempts to
      target children have largely failed. More critically the case of Angola calls
      into question the broader effectiveness and appropriateness of child-centred DDR.
      First, such targeting is inappropriate to distinct post-conflict contexts and
      constructs a 'template child' asserted to be more vulnerable and deserving than
      adult ex-combatants, which does little to further the reintegration of either
      group, or the rights of the child in a conflict context. Second, child-centred
      reintegration efforts tend to deny children agency as actors in their own
      reintegration. Third, such efforts contribute to the normalisation of a much
      larger ideational and structural flaw of post-conflict peace building, wherein
      'success' is construed as the reintegration of large numbers of beneficiaries
      back into the poverty and marginalisation that contributed to conflict in the
      first place.

PMID- 21961185
TI  - Dominant discourses, debates and silences on child labour in Africa and Asia.
AB  - Drawing on the relevant literature, this article explores key debates and
      controversies on child labour in the context of Africa and Asia. It first
      identifies and analyses three dominant discourses on child labour: 1) the work
      free childhoods perspective; 2) the socio-cultural perspective; and 3) the
      political economy perspective. Against the backdrop of these discourses, the
      article goes on to critically examine aspects of child labour that are
      underrepresented in the literature and in international policy circles. It
      concludes by highlighting the importance of grounding children's gendered work
      within the complex material social practices of interconnected histories and
      geographies in which their livelihoods unfold.

PMID- 21961186
TI  - Hydrology and empire: the Nile, water imperialism and the partition of Africa.
AB  - Why did the British march up the Nile in the 1890s? The answers to this crucial
      question of imperial historiography have direct relevance for narratives and
      theories about imperialism, in general, and the partition of Africa in the
      nineteenth century, in particular. They will also influence our understanding of
      some of the main issues in the modern history of the whole region, including
      state developments and resource utilisation. This article presents an alternative
      to dominant interpretations of the partition of Africa and the role of British
      Nile policies in this context. It differs from mainstream diplomatic history,
      which dominates this research field, in its emphasis on how geographical factors
      and the hydrological characteristics of the Nile influenced and framed British
      thinking and actions in the region. Realising the importance of such factors and
      the specific character of the regional water system does not imply less attention
      to traditional diplomatic correspondence or to the role of individual imperial
      entrepreneurs. The strength of this analytical approach theoretically is that it
      makes it possible to locate the intentions and acts of historical subjects within
      specific geographical contexts. Empirically, it opens up a whole new set of
      source material, embedding the reconstruction of the British Nile discourse in a
      world of Nile plans, water works and hydrological discourses.

PMID- 21961187
TI  - The construction of a "population problem" in colonial India, 1919-1947.
AB  - This article examines the construction of a "population problem" among public
      health officials in India during the inter-war period. British colonial officials
      came to focus on India's population through their concern with high Indian infant
      and maternal mortality rates. They raised the problem of population as one way in
      which to highlight the importance of dealing with public health at an all-India
      basis, in a context of constitutional devolution of power to Indians where they
      feared such matters would be relegated to relative local unimportance. While they
      failed to significantly shape government policy, their arguments in support of
      India's 'population problem' nevertheless found a receptive audience in the
      colonial public sphere among Indian intellectuals, economists, eugenicists, women
      social reformers and birth controllers. The article contributes to the history of
      population control by situating its pre-history in British colonial public health
      and development policy and outside the logic of USA's Cold War strategic planning
      for Asia.

PMID- 21961188
TI  - A plague on Bohemia? Mapping the Black Death.

PMID- 21961189
TI  - Liquid politics: water and the politics of everyday life in the modern city.

PMID- 21961190
TI  - Coming out of the Hasidic closet: Jiri Mordechai Langer (1894-1943) and the
      fashioning of homosexual-Jewish identity.
AB  - This essay inaugurates the historical study of the modern homosexual Jewish
      experience before Stonewall. I begin with a historiographic introduction to the
      emerging subfield of gay Jewish history. I then turn to reintroduce Jiri Langer,
      a homosexual and Hasidic writer affiliated with the interwar "Prague circle" (and
      friend of Franz Kafka and Max Brod) into the purview of modern Jewish Studies. I
      take up two questions: first, how Langer reconciled his homosexual and Orthodox
      religious identity; and second, why Langer"s homosexuality became exigent as a
      Jewish question at this particular historical moment. In his key text, Die Erotik
      der Kabbala, Langer engages with the dominant interwar debates on homosexuality,
      but most directly with the work of Hans Bluher, the major theoretician of the
      German Wandervogelbewegung. In the course of correcting Bluher's antisemitic
      claims about Jews and homosexuality, Langer managed to delineate a specifically
      homosexual Jewish identity by renegotiating the relationship between
      homosexuality and Judaism and by adumbrating a history of "gay" Jews. I
      contextualize this long-neglected text within Langer's fascinating biography; the
      debates in the early homosexual rights movement; the particular cultural features
      of the "Prague circle" in which Langer wrote; and the dislocation and devastation
      of Langer's beloved eastern-European Hasidic communities caused by World War I
      communities that Langer experienced as deeply homoerotic.

PMID- 21961191
TI  - "It used to be about the kids": nutrition reform and the Montreal Protestant
      School Board.
AB  - The nutrition programs that developed in Montreal Protestant schools during the
      1970s attest to a deepening awareness of child and adolescent welfare. The
      combination of grassroots activism and government support that brought about
      these initiatives took place in the context of post-Quiet Revolution Quebec, when
      Montrealers were grappling with the role that the newly activist state should
      play in social life. At the same time, school nutrition reform was part of a
      broader ongoing renegotiation of state responsibility. Both in Canada and the
      United States, governments were steadily assuming a mantle of responsibility for
      expanded liberal rights.

PMID- 21961192
TI  - Stamina, speed and adventure: Australian women and competitive cycling in the
      1890s.
AB  - The scholarship surrounding women's cycling in Australia during the 1890s is
      slim. However, a focus on female competitive cycling, just one of many diverse
      cycling activities that women pursued in this era, reveals a rich seam of
      information. Accordingly, this paper surveys endurance riding, adventure touring
      and racing, introducing new historical and biographical detail and highlighting
      the significance of competitive cycling for women in the late nineteenth century.
      The discussion shows that women's competitive cycling constituted a significant
      component of Australian cycling history, and helped to re-define women's identity
      in an era when feminine roles were in flux and the traditional gender order was
      being contested.

PMID- 21961193
TI  - Imagining the absent dead: rituals of bereavement and the place of the war dead
      in German women's art during the First World War.
AB  - Drawing on women's visual responses to the First World War, this article examines
      female mourning in wartime Germany. The unprecedented death toll on the
      battlefronts, military burial practices and the physical distance from the
      remains of the war dead disrupted traditional rituals of bereavement, hindered
      closure and compounded women's grief on the home front. In response to these
      novel circumstances, a number of female artists used their images to reimagine
      funerary customs, overcome the separation from the fallen and express acute
      emotional distress. This article analyses three images produced during the
      conflict by the artists Katharina Heise, Martha Schrag and Sella Hasse, and
      places their work within the civilian experience of bereavement in war. By
      depicting the pain of loss, female artists contested the historical tradition of
      proud female mourning in German society and countered wartime codes of conduct
      that prohibited the public display of emotional pain in response to soldiers'
      deaths. As a largely overlooked body of sources, women's art adds to our
      understanding of the tensions in wartime cultures of mourning that emerged
      between 1914 and 1918.

PMID- 21961194
TI  - Inflammation in rosacea and acne: Implications for patient care.
AB  - Rosacea and acne are chronic inflammatory skin conditions that share an
      inflammatory pathogenesis, but clinically remain quite distinct. Although many
      have long assumed that these conditions are primarily infectious, emerging
      evidence suggests that inflammation plays a critical role in the pathogenesis of
      these disorders. Part of the innate immune system, the antimicrobial and
      proinflammatory cathelicidins, may be downregulated by both azelaic acid and sub
      antimicrobial doxycycline. In acne, the creation of papules, pustules and nodules
      is clearly mediated through immune mechanisms, and the antiinflammatory effects
      of retinoids play a key role in management. Recent observations help us
      understand in greater detail the role that inflammation plays in these two
      diseases, and the mechanisms by which commonly used medications exert their
      effect by modulating inflammatory processes. This review will present and
      synthesize recently acquired information as it relates to inflammatory acne and
      rosacea pathogenesis and clinical management.

PMID- 21961195
TI  - Early intervention program for infants and toddlers with disabilities. Final
      regulations.
AB  - The Secretary issues final regulations governing the Early Intervention Program
      for Infants and Toddlers with Disabilities. These regulations are needed to
      reflect changes made to the Individuals with Disabilities Education Act, as
      amended by the Individuals with Disabilities Education Improvement Act of 2004
      (Act or IDEA).

PMID- 21961197
TI  - Investment in malaria research  has led to strong  pipeline of malaria  vaccines,
      report  suggests.

PMID- 21961196
TI  - William Wright (1735-1819).

PMID- 21961198
TI  - Study suggests influenza vaccination during pregnancy  protects newborns.

PMID- 21961199
TI  - Recombinant-attenuated Salmonella vaccines modified  to reduce virulence.

PMID- 21961200
TI  - Carotid artery stenting.

PMID- 21961201
TI  - Coronary artery stenting.

PMID- 21961202
TI  - Peripheral vessel stenting.

PMID- 21961203
TI  - Politics and Eros in Aristophanes' speech: Symposium 191e-192a and the Comedies.

PMID- 21961204
TI  - The ever-moving soul in Plato's Phaedrus.

PMID- 21961205
TI  - Foam-Born Aphrodite and the mythology of transformation.

PMID- 21961206
TI  - Philology and cuisine in De re coquinaria.

PMID- 21961207
TI  - Dead parrots society.

PMID- 21961208
TI  - The body and its representations in Aristophanes' Thesmophoriazousai: where does
      the costume end?

PMID- 21961209
TI  - Farting for dollars: a note on Agyrrhios in Aristophanes Wealth 176.

PMID- 21961210
TI  - Impersonating the dead: mimes at Roman funerals.

PMID- 21961211
TI  - Models in the management of animal diseases.

PMID- 21961212
TI  - The World Organisation for Animal Health and epidemiological modelling:
      background and objectives.
AB  - The papers in this issue of the Scientific and Technical Review (the Review)
      examine uses of modelling as a tool to supportthe formulation of disease control
      policy and applications of models for various aspects of animal disease
      management. Different issues in model development and several types of models are
      described. The experience with modelling during the 2001 foot and mouth disease
      outbreak in the United Kingdom underlines how models might be appropriately
      applied by decision-makers when preparing for and dealing with animal health
      emergencies. This paper outlines the involvement of the World Organisation for
      Animal Health (OIE) in epidemiological modelling since 2005, with emphasis on the
      outcome of the 2007 questionnaire survey of model usage among Member Countries,
      the subsequent OIE General Session resolution and the 2008 epidemiological
      modelling workshop at the Centers for Epidemiology and Animal Health in the
      United States. Many of the workshop presentations were developed into the papers
      that are presented in this issue of the Review.

PMID- 21961213
TI  - Principles of epidemiological modelling.
AB  - Epidemiological modelling can be a powerful tool to assist animal health policy
      development and disease prevention and control. Models can vary from simple
      deterministic mathematical models through to complex spatially-explicit
      stochastic simulations and decision support systems. The approach used will vary
      depending on the purpose of the study, how well the epidemiology of a disease is
      understood, the amount and quality of data available, and the background and
      experience of the modellers. Epidemiological models can be classified into
      various categories depending on their treatment of variability, chance and
      uncertainty (deterministic or stochastic), time (continuous or discrete
      intervals), space (non-spatial or spatial) and the structure of the population
      (homogenous or heterogeneous mixing). The increasing sophistication of computers,
      together with greater recognition of the importance of spatial elements in the
      spread and control of disease, mean that models which incorporate spatial
      components are becoming more important in epidemiological studies.
      Multidisciplinary approaches using a range of new technologies make it possible
      to build more sophisticated models of animal disease. New generation
      epidemiological models enable disease to be studied in the context of physical,
      economic, technological, health, media and political infrastructures. To be
      useful in policy development, models must be fit for purpose and appropriately
      verified and validated. This involves ensuring that the model is an adequate
      representation of the system under study and that its outputs are sufficiently
      accurate and precise for the intended purpose. Finally, models are just one tool
      for providing technical advice, and should not be considered in isolation from
      data from experimental and field studies.

PMID- 21961214
TI  - Stochastic, spatially-explicit epidemic models.
AB  - Animal disease epidemic models are useful for better understanding both the
      spread and control of disease in a population. While it is advisable that models
      be only as complex as needed, it is often necessary to modify simplifying
      assumptions and thus increase model complexity to better reflect reality. Here,
      the author will examine the need for increasing model complexity by including
      randomness in a model and modifying the assumption of homogeneous mixing, by
      introducing a spatial component into the model. The costs and benefits of these
      changes will be examined.

PMID- 21961215
TI  - Introduction to network analysis and its implications for animal disease
      modelling.
AB  - Social networks analysis (SNA) has recently been used in veterinary epidemiology
      to study livestock movements. A network is obtained by considering livestock
      holdings as nodes in a network and movements among holdings as links among nodes.
      Social networks analysis enables the study of the network as a whole, exploring
      all the relationships among pairs of farms. Highly connected livestock holdings
      in the network can be identified, which can help surveillance and disease
      prevention activities. Observed livestock movement networks in various countries
      have shown an important level of contact heterogeneity and clustering
      (topological, not necessarily geographical or spatial) and understanding the
      architecture of these networks has provided a better understanding of how
      infections may spread. The findings of SNA studies of livestock movement should
      be used to build and parameterise epidemiological models of infection spread in
      order to improve the reliability of the outputs from these models.

PMID- 21961216
TI  - Disease spread models in wild and feral animal populations: application of
      artificial life models.
AB  - The role that wild and feral animal populations might play in the incursion and
      spread of important transboundary animal diseases, such as foot and mouth disease
      (FMD), has received less attention than is warranted by the potential impacts. An
      artificial life model (Sirca) has been used to investigate this issue in studies
      based on spatially referenced data sets from southern Texas. An incursion of FMD
      in which either feral pig or deer populations were infected could result in
      between 698 and 1557 infected cattle and affect an area of between 166 km2 and
      455 km2 after a 100-day period. Although outbreak size in deer populations can be
      predicted bythe size of the local deer population initially infected, the
      resulting outbreaks in feral pig populations are less predictable. Also, in the
      case of deer, the size of potential outbreaks might depend on the season when the
      incursion occurs. The impact of various mitigation strategies on disease spread
      has also been investigated. The approach used in the studies reviewed here
      explicitly incorporates the spatial distribution and relationships between animal
      populations, providing a new framework to explore potential impacts, costs, and
      control strategies.

PMID- 21961217
TI  - Models of macroparasitic infections in domestic ruminants: a conceptual review
      and critique.
AB  - A mathematical model is just a means of representing and manipulating something
      that would not otherwise be accessible. Decision theorists argue that a right
      decision is one that makes the best use of the available information and using
      mathematical models of infectious and parasitic disease can help make sure the
      decision-makers do just that. Seen in this light, models are simply aids to
      thought--and thus, by definition, good models are useful. This paper deals with
      the history of mathematical models of parasitic infections of domestic ruminants.
      It is argued that the early simple forecasting models were very successful, and,
      although the more complicated models that were constructed to improve the
      resolution of the forecasts were mostly failures, the experience gained generated
      a slew of useful, robust models that are still valuable decision-making tools.

PMID- 21961218
TI  - Atmospheric dispersion models and their use in the assessment of disease
      transmission.
AB  - Atmospheric dispersion models can be used to assess the likely airborne spread of
      both plant and animal diseases. These models, often initially developed for other
      purposes, can be adapted and used to study past outbreaks of disease as well as
      operationally to provide advice to those responsible for containing or
      eradicating disease in the event of a specific emergency. The models can be run
      over short periods of time where emissions and infection periods can be
      accurately determined or in situations requiring a statistical approach perhaps
      covering many weeks or even months. They can also be embedded within other
      simulation models, i.e. models which seekto represent a wider variety of disease
      transmission mechanisms. Whilst atmospheric dispersion models have been used
      successfully in a number of instances, they have the potential for wider
      application in the future. To achieve maximum success in these ventures, close
      collaboration between the modellers and scientists from the appropriate range of
      disciplines is required.

PMID- 21961219
TI  - Estimation of foot and mouth disease transmission parameters, using outbreak data
      and transmission experiments.
AB  - Mathematical models for the spread of foot and mouth disease (FMD) have been
      developed and used for a number of purposes in the recent literature. One
      important purpose is predicting the effect of strategies to combat between-farm
      epidemic spread, in support of decision-making on epidemic control. The authors
      briefly review the various modelling approaches, discussing the parameters used
      and how estimates may be obtained for these parameters. They emphasise that, in
      addition to the estimation of FMD transmission parameters, the choice of model
      structure (including the number and type of parameters used) is also crucial. Two
      gaps in the knowledge of FMD transmission, related to model construction and
      parameter quantification, are identified: transmission between different species
      and the way in which vaccination affects such transmission, and route-specific
      FMD transmission properties. In particular, the authors pay attention to the role
      that small-scale transmission experiments can play in bridging these gaps.

PMID- 21961220
TI  - Destructive tension: mathematics versus experience--the progress and control of
      the 2001 foot and mouth disease epidemic in Great Britain.
AB  - The 2001 foot and mouth disease epidemic in Great Britain was characterised by
      control using both traditional and novel methods, some resulting from conclusions
      of mathematical models. Seven days before the implementation of the novel
      controversial automatic pre-emptive culling of all susceptible livestock on
      premises adjacent to infected premises (the 'contiguous cull'), the spread of
      infection had already been controlled by a combination of the traditional
      stamping out policy with a national movement ban on livestock. A second
      controversial novel policy requiring the slaughter of sheep within 3 km of
      premises on which disease had been confirmed (the 3-km cull) also commenced after
      the peak of infection spread, was untargeted and took several weeks to complete;
      serosurveillance of culled sheep detected infection in only one flock, suggesting
      that cryptic infection of sheep was not propagating the epidemic. Extensive post
      epidemic serological surveillance of sheep found only a small number of
      seropositive animals in a very few flocks, suggesting that foot and mouth disease
      may self-limit in extensive sheep populations. The epidemic was finally brought
      to an end following the introduction of enhanced agricultural movement
      restrictions and biosecurity measures. A welfare culling scheme of unaffected
      animals was required to support the prolonged national livestock movement ban.
      The models that supported the contiguous culling policy were severely flawed,
      being based on data from dissimilar epidemics; used inaccurate background
      population data, and contained highly improbable biological assumptions about the
      temporal and quantitative parameters of infection and virus emission in infected
      herds and flocks.

PMID- 21961221
TI  - Approaches for evaluating veterinary epidemiological models: verification,
      validation and limitations.
AB  - The evaluation of models of the spread and control of animal diseases is crucial
      if these models are to be used to inform decisions about the control or
      management of such diseases. Two key steps in the evaluation of epidemiological
      models are model verification and model validation. Verification is the
      demonstration that a computer-driven model is operating correctly, and conforms
      to its intended design. Validation refers to the process of determining how well
      a model corresponds to the system that it is intended to represent. For a
      veterinary epidemiological model, validation would address such issues as how
      well the model represents the dynamics of the disease in question in the
      population to which this model is applied, and how well the model represents the
      application of different measures for disease control. Just as the development of
      epidemiological models is a subjective, continuous process, subject to change and
      refinement, so too is the evaluation of models. The purpose of model evaluation
      is not to demonstrate that a model is a 'true' or accurate' representation of a
      system, but to subject it to sufficient scrutiny so that it may be used with an
      appropriate degree of confidence to aid decision-making. To facilitate model
      verification and validation, epidemiological modellers should clearly state the
      purpose, assumptions and limitations of a model; provide a detailed description
      of the conceptual model; document those steps already taken to test the model;
      and thoroughly describe the data sources and the process used to produce model
      input parameters from those data.

PMID- 21961222
TI  - A sensitivity analysis of the New Zealand standard model of foot and mouth
      disease.
AB  - Disease simulation models can be a valuable tool for planning a response to
      exotic disease incursions, as they provide a fast, low-cost mechanism for
      identifying the likely outcomes of a range of outbreak scenarios and disease
      control strategies. To use these tools effectively and with confidence, decision
      makers must understand the simplifications and framing assumptions that underlie
      a model's structure. Sensitivity analysis, the analytical process of identifying
      which input variables are the key drivers of the model's output, is a crucial
      process in developing this understanding. This paper describes the application of
      a sampling-based sensitivity analysis to the New Zealand standard model (NZSM).
      This model is a parameter set developed for the InterSpread Plus model platform
      to allow the exploration of different outbreak scenarios for an epidemic of foot
      and mouth disease in New Zealand. Based on 200 iterations of the NZSM, run for a
      simulation period of 60 days, settings related to farm-to-saleyard movements and
      the detection of disease during the active surveillance phase of the epidemic had
      the greatest influence on the predicted number of infected premises. A small
      number of counter-intuitive findings indicated areas of model design,
      implementation and/or parameterisation that should be investigated further. A
      potentially useful result from this work would be information to aid the grouping
      or elimination of non-influential model settings. This would go some way towards
      reducing the overall complexity of the NZSM, while still allowing it to remain
      fit for purpose.

PMID- 21961223
TI  - Foot and mouth disease model verification and 'relative validation' through a
      formal model comparison.
AB  - Researchers from Australia, New Zealand, Canada and the United States
      collaborated to validate their foot and mouth disease models--AusSpread,
      InterSpread Plus and the North American Animal Disease Spread Model--in an effort
      to build confidence in their use as decision-support tools. The final stage of
      this project involved using the three models to simulate a number of disease
      outbreak scenarios, with data from the Republic of Ireland. The scenarios
      included an uncontrolled epidemic, and epidemics managed by combinations of
      stamping out and vaccination. The predicted numbers of infected premises, the
      duration of each epidemic, and the size of predicted outbreak areas were
      compared. Relative within-model between-scenario changes resulting from different
      control strategies or resource constraints in different scenarios were quantified
      and compared. Although there were differences between the models in absolute
      outcomes, between-scenario comparisons within each model were similar. In all
      three models, early use of ring vaccination resulted in the largest drop in
      number of infected premises compared with the standard stamping-out regimen. This
      consistency implies that the assumptions made by each of the three modelling
      teams were appropriate, which in turn serves to increase end-user confidence in
      predictions made by these models.

PMID- 21961224
TI  - The role of models in estimating consequences as part of the risk assessment
      process.
AB  - The degree of disease risk represented by the introduction, spread, or
      establishment of one or several diseases through the importation of animals and
      animal products is assessed by importing countries through an analysis of risk.
      The components of a risk analysis include hazard identification, risk assessment,
      risk management, and risk communication. A risk assessment starts with
      identification of the hazard(s) and then continues with four interrelated steps:
      release assessment, exposure assessment, consequence assessment, and risk
      estimation. Risk assessments may be either qualitative or quantitative. This
      paper describes how, through the integration of epidemiological and economic
      models, the potential adverse biological and economic consequences of exposure
      can be quantified.

PMID- 21961225
TI  - Lexicon of disease spread modelling terms.
AB  - Over the past decade there has been a notable increase in the magnitude and
      variety of modelling work in the realm of animal health. Similarly, there has
      been an increase in the extent to which modelling is used as a component in the
      development of animal health policy. The increased dependency on modelling
      creates a need to enhance understanding and linkages between policy-makers (those
      that pose the policy or scientific questions, commission modelling work and use
      model outputs in the development of policy), intermediaries (those that are
      responsible for working with modellers and communicating model results to policy
      makers), and modellers. Development of a lexicon of disease spread modelling
      terms can help support clear communication and collaboration between all players.

PMID- 21961226
TI  - The use of modelling to evaluate and adapt strategies for animal disease control.
AB  - Disease is often associated with debilitating clinical signs, disorders or
      production losses in animals and/or humans, leading to severe socio-economic
      repercussions. This explains the high priority that national health authorities
      and international organisations give to selecting control strategies for and the
      eradication of specific diseases. When a control strategy is selected and
      implemented, an effective method of evaluating its efficacy is through modelling.
      To illustrate the usefulness of models in evaluating control strategies, the
      authors describe several examples in detail, including three examples of
      classification and regression tree modelling to evaluate and improve the early
      detection of disease: West Nile fever in equids, bovine spongiform encephalopathy
      (BSE) and multifactorial diseases, such as colony collapse disorder (CCD) in the
      United States. Also examined are regression modelling to evaluate skin test
      practices and the efficacy of an awareness campaign for bovine tuberculosis
      (bTB); mechanistic modelling to monitor the progress of a control strategy for
      BSE; and statistical nationwide modelling to analyse the spatio-temporal dynamics
      of bTB and search for potential risk factors that could be used to target
      surveillance measures more effectively. In the accurate application of models, an
      interdisciplinary rather than a multidisciplinary approach is required, with the
      fewest assumptions possible.

PMID- 21961227
TI  - Epidemiological models to assist the management of highly pathogenic avian
      influenza.
AB  - In recent decades, epidemiological models have been used more and more frequently
      as a tool for the design of programmes for the management of infectious diseases
      such as highly pathogenic avian influenza. Predictive models are used to simulate
      the effects of various control measures on the spread of the infection;
      analytical models are used to analyse data from outbreaks and experiments. A key
      parameter in these models is the reproduction ratio, which indicates to what
      degree the virus can be transmitted in the population. Parameters obtained from
      real data using the analytical models can be used subsequently in predictive
      models to evaluate control strategies or surveillance programmes. Examples of the
      use of these models are described in the current paper.

PMID- 21961228
TI  - Adapting existing models of highly contagious diseases to countries other than
      their country of origin.
AB  - Many countries do not have the resources to develop epidemiological models of
      animal diseases. As a result, it is tempting to use models developed in other
      countries. However, an existing model may need to be adapted in order for it to
      be appropriately applied in a country, region, or situation other than that for
      which it was originally developed. The process of adapting a model has a number
      of benefits for both model builders and model users. For model builders, it
      provides insight into the applicability of their model and potentially the
      opportunity to obtain data for operational validation of components of their
      model. For users, it is a chance to think about the infection transmission
      process in detail, to review the data available for modelling, and to learn the
      principles of epidemiological modelling. Various issues must be addressed when
      considering adapting a model. Most critically, the assumptions and purpose behind
      the model must be thoroughly understood, so that new users can determine its
      suitability for their situation. The process of adapting a model might simply
      involve changing existing model parameter values (for example, to better
      represent livestock demographics in a country or region), or might require more
      substantial (and more labour-intensive) changes to the model code and conceptual
      model. Adapting a model is easier if the model has a user-friendly interface and
      easy-to-read user documentation. In addition, models built as frameworks within
      which disease processes and livestock demographics and contacts are flexible are
      good candidates for technology transfer projects, which lead to long-term
      collaborations.

PMID- 21961229
TI  - Using simplified models to communicate the importance of prevention, detection
      and preparedness before a disease outbreak.
AB  - Frontline farm workers and veterinary-policy-makers are arguably in the best
      positions to influence prevention, detection, and preparedness-for-control of
      farm animal diseases. It is important that such individuals make biologically
      sound decisions concerning the daily management and regulation of the health of
      animals. Such decisions should be based on a good understanding of key principles
      of disease spread and control. This paper summarises these principles, as
      described in previous publications, into simple models. These models may be used
      to communicate concepts to readers who may not have time to study more complex
      models. These models illustrate the relationship between the development of new
      disease cases (from existing cases, i.e., the reproductive ratio R) and (i) the
      duration of the period during which existing cases are available as infectious,
      (ii) contact rates, (iii) transmission rates and (iv) susceptibility.
      Understanding these concepts through models has great utility, facilitating
      better decisions for disease prevention, detection and preparedness-for-control,
      before an outbreak becomes unmanageable. These basic concepts apply to all animal
      species, including humans.

PMID- 21961230
TI  - Epidemiological models to support animal disease surveillance activities.
AB  - Epidemiological models have been used extensively as a tool in improving animal
      disease surveillance activities. A review of published papers identified three
      main groups of model applications: models for planning surveillance, models for
      evaluating the performance of surveillance systems and models for interpreting
      surveillance data as part of ongoing control or eradication programmes. Two
      Danish examples are outlined. The first illustrates how models were used in
      documenting country freedom from disease (trichinellosis) and the second
      demonstrates how models were of assistance in predicting the risk of future
      cases, detected and undetected, of a waning infection of bovine spongiform
      encephalopathy. Both studies were successful in advancing European policy changes
      to reduce the cost of surveillance to appropriate levels given the magnitude of
      the respective hazards.

PMID- 21961231
TI  - Stochastic models to simulate paratuberculosis in dairy herds.
AB  - Stochastic simulation models are widely accepted as a means of assessing the
      impact of changes in daily management and the control of different diseases, such
      as paratuberculosis, in dairy herds. This paper summarises and discusses the
      assumptions of four stochastic simulation models and their use in the design of
      certification, surveillance, and control strategies for paratuberculosis in
      cattle herds. A detailed comparison is made between the Dutch JohneSSim and the
      Danish PTB-Simherd, using the same context of a set of control strategies in a
      typical Dutch/Danish herd. The conclusion is that while the models are somewhat
      different in their underlying principles and do put slightly different values on
      the different strategies, their overall findings are similar. Therefore,
      simulation models may be useful in planning paratuberculosis strategies in dairy
      herds, although as with all models caution is warranted when interpreting and
      generalising the results.

PMID- 21961232
TI  - Simulating the bovine spongiform encephalopathy situation in Japan.
AB  - Despite various measures taken by the Japanese government to protect the cattle
      population from exposure to the bovine spongiform encephalopathy (BSE) agent, the
      first case of BSE was detected in September 2001. Subsequently, BSE surveillance
      was enhanced, involving mandatory reporting and investigation of all clinical BSE
      suspects, and testing of fallen stock and all cattle slaughtered for human
      consumption. Tests on over nine million cattle led to the detection of 35
      additional cases by the end of May 2009. Using the surveillance data and other
      information as input variables, models were developed to explore the possible
      source of introduction of BSE into Japan, evaluate the effectiveness of control
      measures, estimate the prevalence of BSE in different birth cohorts, predict a
      future BSE epidemic, and simulate the impact of changes in surveillance
      strategies. Despite difficulties associated with the availability and uncertainty
      of some of the input variables, these models provided an objective insight into
      the BSE situation in Japan.

PMID- 21961233
TI  - Modelling the feasibility of bovine tuberculosis eradication in Argentina.
AB  - The ability of countries to control and eradicate bovine tuberculosis (TB) has
      been jeopardised by various epidemiological and ecological features of the
      disease. The authors have used epidemiological modelling to develop an analytical
      framework to assess the likely success of a national TB eradication programme in
      Argentina. Study results suggest that the current control programme is
      financially feasible in the long term. However, considering that the costs of the
      TB eradication programme in Argentina are entirely borne by the producer, the
      initial investment required and the long-term horizon needed to gain revenue may
      prevent producers from endorsing the programme. Regionalised programmes that
      allow differential control strategies to be implemented in specific regions may
      increase the likelihood of success. This methodological approach could be
      extended to design and evaluate control and eradication programmes for TB and
      other infectious diseases in other regions of the world.

PMID- 21961234
TI  - [Y-chromosome microdeletions do not affect the outcomes of ICSI for infertile
      males].
AB  - OBJECTIVE: To compare the outcomes of intracytoplasmic sperm injection (ICSI) for
      infertile males with Y-chromosome microdeletions and for those with azoospermia
      or severe oligospermia but without Y-chromosome microdeletions. METHODS: We
      retrospectively analyzed 56 cycles of ICSI for 48 infertile cases with Y
      microdeletions (Group A) and 94 cycles for 90 cases with azoospermia or severe
      oligospermia but without Y-chromosome microdeletions (Group B) during the same
      period. We compared the two groups in the females' age, duration of infertility,
      males' age, number of oocytes retrieved, number of ICSI oocytes, fertilization
      rate, good embryo rate, number of embryos transferred, implantation rate,
      clinical pregnancy rate, abortion rate, live birth rate and babies' sexes.
      RESULTS: There were no significant differences between Groups A and B in the
      females' age, duration of infertility, males' age, number of oocytes retrieved,
      number of ICSI oocytes and number of embryos transferred (P > 0.05), nor in the
      rates of fertilization (69.0% vs 73.2%), good embryos (53.3% vs 48.7%),
      implantation (24.0% vs 30.3%), biochemical pregnancy (41.1% vs 44.7%), clinical
      pregnancy (37.5% vs 35.1%), early abortion (4.8% vs 6.1%) and live birth (35.7%
      vs 29.2%) (P > 0.05). CONCLUSION: Y-chromosome microdeletions do not affect the
      outcomes of ICSI. The affected couples should be informed of the necessity of
      prenatal genetic diagnosis before embryo implantation and the inevitability of
      vertical transmission to male offspring.

PMID- 21961235
TI  - [Screening PIAS2-interacting proteins in the mouse using the yeast two-hybrid
      system].
AB  - OBJECTIVE: To screen and identify PIAS2-interacting proteins from the mouse
      spermatogonial cDNA library using the yeast two-hybrid system, and to investigate
      the action mechanism of PIAS2 in spermatogenesis. METHODS: With pGBKT7-PIAS2 as a
      bait plasmid, the positive clones interacting with pGBKT7-PIAS2 were screened
      from the mouse spermatogonial cDNA library, the inserted fragments were sequenced
      and underwent bioinformatic analysis, and their interaction was verified using
      the yeast two-hybrid system. RESULTS: Through screening, sequencing, homology
      analysis and yeast two-hybrid verification, we obtained 8 different candidate
      proteins interacting with PIAS2, including Cyfip2, Psmb3, Nmel, nischarin,
      Ints10, Nsun5, Gnb211 and Ndufaf3. CONCLUSION: Eight different genes were
      successfully obtained using the yeast two-hybrid system, and their encoding
      proteins interacted with PIAS2, which might be related with male fertility
      regulation. Our findings have offered some new clues to the action mechanism of
      PIAS2 in spermatogenesis.

PMID- 21961236
TI  - [Significance of nerve growth factor expression in the prostate tissue of
      spontaneously hypertensive rats].
AB  - OBJECTIVE: To investigate the changes of the expressions of the nerve growth
      factor (NGF) and its mRNA in the prostate tissues of spontaneously hypertensive
      rats (SHR) of different ages and their significance. METHODS: SHRs and
      normotensive Wistar Kyoto (WKY) rats were killed at 1 month (young), 6 months
      (adult) and 12 months (aging), respectively, 5 in each group. Their prostate
      indexes were calculated, and the expressions of NGF and its mRNA in the ventral
      prostate tissue were detected by immunohistochemistry and RT-PCR. RESULTS: The
      prostate indexes of the SHR and WKY groups were 1.16 +/- 0.06 and 1.03 +/- 0.09
      at 1 month, 1.12 +/- 0.14 and 0.93 +/- 0.07 at 6 months, and 1.11 +/- 0.05 and
      0.96 +/- 0.09 at 12 months, significantly higher in the former group than in the
      latter either at 6 or at 12 months (P < 0.05), but with no obvious difference at
      1 month (P > 0.05). The expressions of NGF and its mRNA in the ventral prostate
      tissue were detected in all groups, and elevated gradually with the increase of
      age (P < 0.05). Among those of the same age, the expression levels were markedly
      higher in the SHR than in the WKY group (P < 0.05). CONCLUSION: In SHRs with
      benign prostate hyperplasia (BPH), the enhanced excitation of the sympathetic
      nervous system may be a common mechanism underlying BPH and hypertension, and NGF
      plays an important role in it.

PMID- 21961237
TI  - [Spermatogenic cell apoptosis and expressions of Bcl-2 and Bax proteins after
      burying the testis in the inguinal pocket].
AB  - OBJECTIVE: To observe the apoptosis of spermatogenic cells and the expressions of
      Bcl-2 and Bax proteins after burying the testis in the inguinal pocket, and to
      investigate their relationship. METHODS: We randomly divided 36 healthy male New
      Zealand white rabbits into an experimental group (n = 18) and a control group (n
      = 18). Models were established by burying testes in the inguinal pocket in the
      experimental group, while the controls were left untreated. At the end of the 8th
      week after surgery, 6 animals were randomly taken from each group for measurement
      of the testis surface temperature and testicular biopsy. The apoptosis of
      spermatogenic cells in the testis tissues was detected by TUNEL assay, and the
      expressions of Bcl-2 and Bax proteins determined by immunohistochemistry and
      imaging analysis. RESULTS: At 8 weeks after burying the testis in the inguinal
      pocket, the testicular surface temperature was significantly higher in the
      experimental group than in the control ([ 38.02 +/- 0.36] degrees C vs [36.15 +/-
      0.64 ] degrees C, P < 0.05), and so was the apoptosis index (AI) of spermatogenic
      cells ([89.69 +/- 3.76] % vs [7.73 +/- 4.95 ] %, P < 0.05). The expression of the
      Bax protein in the testis was significantly increased, while that of the Bcl-2
      protein remarkably decreased in the experimental group as compared with the
      control group (P < 0.05). The apoptotic cells were mostly primary spermatocytes
      and round spermatids. CONCLUSION: Elevated local temperature of the testis buried
      in the inguinal pocket increases the apoptosis of spermatogenic cells, and the
      spermatogenic cell apoptosis is highly correlated with the decreased expression
      of Bcl-2 and increased expression of Bax. The changes in the expressions of Bcl-2
      and Bax proteins were a main mechanism behind the temperature elevation-induced
      apoptosis of spermatogenic cells.

PMID- 21961238
TI  - [Quercetin induces the apoptosis of human PC-3 cells].
AB  - OBJECTIVE: To study the effect of quercetin on the apoptosis of human PC-3 cells.
      METHODS: Human PC-3 cells were cultured in vitro and then treated with quercetin
      at the concentrations of 50, 100, 150, 200 and 250 micromol/L. The inhibition
      rate of quercetin on the PC-3 cells was detected by MTT, the apoptosis of the
      cells determined by flow cytometry, and the changes of the cellular
      ultramicrostructure observed by transmission electron microscopy. RESULTS:
      Quercetin markedly inhibited the proliferation of PC-3 cells in vitro in a time-
      and dose-dependent manner. Its inhibition rates were (3.01 +/- 1.32)%, (4.84 +/-
      1.73)%, (20.35 +/- 1.30)%, (16.78 +/- 1.89)% and (27.25 +/- 4.01)% at 24 hours,
      and (10.18 +/- 1.16)%, (6.22 +/- 0.04)%, (24.29 +/- 4.19)%, (22.4 +/- 4.26)% and
      (41.42 +/- 5.43)% at 48 hours in the 50, 100, 150, 200 and 250 micromol/L groups,
      respectively, with statistical significance at the concentration of > 150
      micromol/L (P < 0.05). Flow cytometry showed that the apoptosis of PC-3 cells was
      increased with the elevated concentration and prolonged time of Quercetin
      treatment, (19.10 +/- 0.28)% and (26.55 +/- 0.78)% at 24 hours, and (27.65 +/-
      1.06)% and (38.30 +/- 5.96)% at 48 hours in the 150 and 200 micromol/L groups,
      respectively (P < 0.05). Typical changes in the morphology of the cells were
      observed under the transmission electron microscope. CONCLUSION: Quercetin can
      inhibit the proliferation and induce the apoptosis of human PC-3 cells, but its
      action mechanism remains to be further investigated.

PMID- 21961239
TI  - [Local injection of gentamycin for female urethral syndrome: a clinical study].
AB  - OBJECTIVE: To observe the therapeutic effect of local antibiotic injection into
      the female prostate on female urethral syndrome (FUS), and search for an
      effective treatment for this disease. METHODS: This study included 163 FUS
      patients treated in the out-patient department between July 2009 and December
      2010. According to the visiting order, the patients were randomly assigned to
      Groups A (n = 58), B (n = 55) and C (n = 50). All underwent routine treatment.
      Inaddition Group A received local injection of 2 ml of 80 000 U gentamycin + 2 ml
      of lidocaine, and Group B 2 ml of normal saline + 2 ml of lidocaine, both
      injected into the distal segment of the urethral back wall where the female
      prostate is located, twice a week for 3 weeks. The therapeutic effects were
      evaluated according to the changes of the patients' independent symptom scores at
      2 and 4 weeks after the treatment. Disappearance of the symptoms was considered
      as "curative" , > 1/2 reduction in the symptom score as "obviously effective",
      1/2 - > 1/4 reduction in the symptom score as "effective", and < 1/4 reduction or
      increase in the symptom score as "ineffective". RESULTS: At 2 weeks after the
      treatment, the total effectiveness rate was significantly higher in Group A
      (77.5%) than in B (67.3%) and C (68.0%) (P < 0.05), but with no statistically
      significant difference between B and C (P > 0.05). At 4 weeks, the total
      effectiveness rate of Group A was slightly decreased, but still remarkably higher
      than that of group B or C (P < 0.05). CONCLUSION: Local injection of gentamycin
      into the female prostate is effective for the treatment of female urethral
      syndrome.

PMID- 21961240
TI  - [Location of Dctn1 in the mouse testis and sperm and its role in spermiogenesis].
AB  - OBJECTIVE: To investigate the role of dynactin 1 (Dctn1) in the process of mouse
      spermiogenesis. METHODS: Western blot and indirect immunofluorescence were used
      to analyze the expression and location of Dctn1 in the mouse testis and
      spermatozoa. The highest efficiency of small interference RNA (siRNA) was
      verified by GC2-spd cell line in vitro and in vivo studies, respectively. Dctn1
      siRNA mixed with the indicator (0.4% trypan blue) was injected into the
      seminiferous tubules of 3-week-old ICR mice through rete testis microinjection,
      and negative control siRNA injected into the control testes. The normal group
      included 3-week-old ICR mice that did not receive any treatment. Spermatozoa were
      collected from the cauda epididymis 3 weeks after siRNA injection for
      morphological analysis. RESULTS: Dctn1 was mainly localized in the tail of
      spermatozoa. After interference, the sperm tail abnormality in the Dctn1 siRNA
      group was (23.57 +/- 0.55)%, significantly higher than (12.35 +/- 2.29)% in the
      control (P < 0.01, n = 3), and it was (3.37 +/- 0.69)% in the normal group.
      CONCLUSION: Dctn1 plays an important role in mouse spermiogenesis, and mainly
      affects the formation of the tail of spermatozoa.

PMID- 21961241
TI  - [Inhibition of SRC-1 expression in prostate cancer cells by RNAi and its
      significance].
AB  - OBJECTIVE: To investigate the inhibition of the expression of steroid receptor
      coactivator-1 (SRC-1) in the LNCap cell line through RNA interference (RNAi) and
      the effect of the silenced SRC-1 gene on LNCap cells. METHODS: The experiment
      included four groups: siRNA transfection, siRNA negative control, bland vehicle
      (with Lipofectamine 2000 but no siRNA), and blank control (with neither
      Lipofectamine 2000 nor siRNA). LNCap cells were transfected with designed siRNA
      using the liposomes method, the expressions of SRC-1 determined by Q-PCR and
      Western blot, and the proliferation of the LNCap cells detected by the CCK-8
      method. RESULTS: The expression of SRC-1 mRNA in the transfected LNCap cells was
      decreased by 35% at 24 hours and 77% at 48 hours, with statistically significant
      differences from the blank control group (P < 0.05). The SRC-1 protein expression
      of the transfected group was 0.359 +/- 0.034 at 24 hours and 0.257 +/- 0.065 at
      48 hours, markedly decreased as compared with that of the negative control (0.782
      +/- 0.078 and 0.766 +/- 0.043) , bland vehicle (0.840 +/- 0.013 and 0.786 +/-
      0.051), and blank control group (0.816 +/- 0.065 and 0.805 +/- 0.107) (P < 0.05).
      The LNCap cell growth inhibition rates were 25%, 52%, 55% and 60% at 24, 48, 72
      and 96 hours, respectively. CONCLUSION: The expression of SRC-1 is correlated
      with the growth of LNCap cells; its high expression in androgen-independent
      prostate cancer cells may be involved in the progression to androgen
      independence. Inhibiting the expression of SRC-1 may be an option for the
      treatment of androgen-dependent prostate cancer.

PMID- 21961242
TI  - [ERK and P38MAPK expressions and human sperm motility].
AB  - OBJECTIVE: To compare the phosphorylation and protein expression of extracellular
      signal regulated protein kinase (ERK) and P38 mitogen activated protein kinase
      (P38 MAPK) in the ejaculated spermatozoa of healthy volunteers and asthenospermia
      males, and to explore the correlation of ERK and P38 MAPK with human sperm
      motility. METHODS: Semen samples were collected from 20 healthy volunteers (sperm
      concentration > or = 20 x 10(6)/ml, grade a sperm > or = 25% or grade a + b sperm
      > or = 50%) and 20 infertile males with asthenospermia (sperm concentration > or
      = 20 x 10(6)/ml, grade a sperm < 25% and grade a + b sperm < or = 40%) and
      classified as a control and an asthenospermia group. Total protein in spermatozoa
      was extracted from all the subjects, and Western blotting was used to detect
      phosphorylation and protein expression levels of ERK and P38 MAPK. RESULTS:
      Compared with the control group, the protein expression levels of ERK and P38
      MAPK and the phosphorylation level of P38 MAPK were significantly increased in
      the asthenospermia group (P < 0.05), but there were no statistically significant
      differences in the phosphorylation level of ERK between the two groups (P >
      0.05). CONCLUSION: The up-regulated protein expressions of ERK and P38MAPK and
      increased phosphorylation level of P38 MAPK in human sperm may be involved in the
      pathogenesis of asthenospermia.

PMID- 21961243
TI  - [Ultrasound-guided transrectal microwave ablation of the prostate in dogs].
AB  - OBJECTIVE: To investigate the feasibility and safety of ultrasound-guided
      transrectal microwave ablation in reducing the prostate volume. METHODS:
      Ultrasound-guided transrectal microwave ablation of both sides of the prostate
      was conducted on experimental dogs with the output volume of 30W for 120 seconds.
      The dogs were sacrificed on the very day of the ablation, and the prostate and
      its surrounding tissues were excised for observation of the thermal lesions and
      pathological examination. RESULTS: A total of 12 thermal lesions were achieved on
      the two sides of the prostate. The ultrasonogram manifested dense echo and
      increasing extent in the ablated area, and then an irregular heterogeneous
      echogenic area and clearly differentiated margin. Pathological examination of the
      gross specimen showed a little stagnant blood under the rectal mucous, the
      urethra and bladder not injured, and the thermal lesions elliptical, clearly
      margined and with the mean size of (0.94 +/- 0.30) cm3. CONCLUSION: Ultrasound
      guided transrectal microwave ablation of the prostate can effectively cause
      coagulative necrosis of the local tissue without inflicting thermal injury upon
      the surrounding tissues. Conventional grayscale ultrasound can give a real
      time'display of the extent of thermal lesion and the whole process of the
      ablation.

PMID- 21961244
TI  - [Correlation of CD82 and hTERT expressions and HPV infection with penile cancer].
AB  - OBJECTIVE: To study the correlation of the expressions of CD82 and hTERT and HPV
      infection with the clinical pathological features of penile cancer and identify
      their prognostic significance in the lymphatic metastasis of the disease.
      METHODS: A total of 44 patients underwent partial or radical penectomy and lymph
      node dissection. The expressions of CD82 and hTERT were determined by
      immunohistochemistry, and HPV infection was detected by PCR. RESULTS: The
      positive rates of CD82, hTERT, and HPV DNA in penile carcinoma were 47.7%, 38.6%
      and 25.9%, respectively. The amplified HPV DNA was HPV-16. The pathological stage
      and hTERT expression were positively correlated with inguinal lymph node
      metastasis of penile cancer (P = 0.032, P = 0.041), and so was the pathological
      stage with the expression of CD82 (P = 0.045), but neither the pathological
      stage, nor the expression of CD82 or the positive rate of HPV DNA showed any
      correlation with lymph node metastasis (P = 0.627, P = 0.094, P = 0.633).
      CONCLUSION: The pathological grade and hTERT expression are independent
      prognostic factors for lymph node metastasis in penile carcinoma. These features
      help the prognosis and identification of the patient at the risk of nodal
      metastasis.

PMID- 21961245
TI  - [Urethral dilation with a zebra guidewire-guided fascia dilator for complex
      urethral stricture after hypospadias surgery].
AB  - OBJECTIVE: To evaluate the clinical effect of urethral dilation with a zebra
      guidewire-guided fascia dilator in the treatment of complex urethral stricture
      after hypospadias surgery. METHODS: This study included 12 cases of complex
      urethral stricture after hypospadias surgery that had failed to respond to other
      urethral dilation therapies. A zebra guidewire was put into the urethra via a
      ureteroscope placed in through a suprapubic puncture hole. Then a fascia dilator
      was inserted along the zebra guidewire for urethral dilation. A silicone catheter
      was reserved for 2 weeks after the dilation. RESULTS: All the 12 patients
      achieved smooth urination after removal of the catheter. During the 6 - 28 months
      follow-up, 8 of the cases were cured after 1 - 6 regular urethral dilations and
      the other 4 experienced no more dysuria. CONCLUSION: Urethral dilation with a
      zebra guidewire-guided fascia dilator is a safe and effective method for the
      treatment of complex urethral stricture after hypospadias surgery.

PMID- 21961246
TI  - [Prostate cancer with five different histological features: a case report and
      review of the literature].
AB  - OBJECTIVE: To study the clinical manifestations, pathological characteristics and
      treatment methods of prostate cancer with five different histological features.
      METHODS: We reported 1 case of prostate cancer with five different histological
      features and further analyzed the diagnosis, pathology and treatment of the
      disease by reviewing the relevant literature. RESULTS: The patient was an 84-year
      old male, admitted due to difficult urination and dribbling urine for 1 year,
      hematuria for 8 months and deterioration for 2 weeks. Prostate cancer was
      indicated by rectal examination, ultrasonography, CT, MRI and PSA, and confirmed
      by biopsy. Considering the general condition of the patient, we performed
      electrotransurethral resection under epidural anesthesia to alleviate his urinary
      symptoms and remove suspected tumor tissues. Postoperative pathology showed the
      case to be prostate adenocarcinoma, histologically characterized by cribriform
      carcinoma, acinar carcinoma, diffuse invasive carcinoma, ductal carcinoma, and
      mucinous adenocarcinoma, with a Gleason score of 9. Bicalutamide and goserelin
      were administered postoperatively. Systemic metastasis occurred 10 months later,
      and the patient died 1 year after the operation. CONCLUSION: Prostate cancer with
      five different histological features is extremely rare. Its early diagnosis is
      difficult and mainly depends on pathological and immunohistochemical
      examinations, and radical prostatectomy can be considered for its treatment.

PMID- 21961247
TI  - [Spermatic cord liposarcoma: a case report and review of the literature].
AB  - OBJECTIVE: To explore the clinical features and treatment of spermatic cord
      liposarcoma (SCL). METHODS: We retrospectively analyzed the clinical data of a
      case of SCL, reviewed the related literature and investigated the diagnosis and
      treatment of the disease. RESULTS: The patient underwent tumor resection and left
      inguinal orchidectomy. Postoperative pathology confirmed the case to be s SCL.
      Neither recurrence nor metastasis was found during the five-month follow-up.
      CONCLUSION: SCL is a rare medical condition with no specific imaging and
      laboratory features. Radical orchidectomy with wide local excision of the mass is
      recommended for its treatment, and adjuvant radiotherapy can be considered in
      intermediately or highly differentiated tumors and recurrent liposarcomas, while
      the role of chemotherapy is not well-defined.

PMID- 21961248
TI  - [Transurethral thulium laser urethrotomy for urethral stricture].
AB  - OBJECTIVE: To evaluate the effect of endourethrotomy with thulium laser as a
      minimally invasive treatment for urethral stricture. METHODS: We treated 36 cases
      of urethral stricture or atresia by endourethrotomy with thulium laser, restored
      the urethral continuity by vaporization excision of the scar tissue, and observed
      the clinical effects and complications. RESULTS: The mean operation time was 35
      min, ranging from 10 to 90 min. Smooth urination was achieved after 2-6 weeks of
      catheter indwelling, with no urinary incontinence. The patients were followed up
      for 4-24 (mean 12) months, during which 27 did not need any reintervention, 5
      developed urinary thinning but cured by urethral dilation, 3 received another
      laser urethrotomy for previous negligence of timely urethral dilation, and the
      other 1 underwent open urethroplasty. CONCLUSION: Thulium laser urethrotomy is a
      safe and effective minimally invasive option for short urethral stricture, which
      is also suitable for severe urethral stricture and urethral atresia. Its short
      term outcome is satisfactory, but its long-term effect remains to be further
      observed.

PMID- 21961249
TI  - [Hereditary tendency of varicocele].
AB  - OBJECTIVE: To investigate the hereditary tendency of varicocele. METHODS: We
      included in this study 112 varicocele patients, 117 direct male relatives of the
      patients, and 100 healthy men as controls. We compared the incidence of
      varicocele tween the direct relative group and the control group. RESULTS: The
      direct male relatives of the varicocele patients had a significantly higher
      incidence of varicocele than the healthy controls (36.8% vs 17%, P < 0.05).
      CONCLUSION: The increased incidence of varicocele in the direct male relatives of
      the patients indicated a hereditary tendency of the disease.

PMID- 21961250
TI  - [Surgical options for benign prostatic hyperplasia: impact on sexual function and
      risk factors].
AB  - Benign prostatic hyperplasia (BPH) is a common problem among elderly males.
      Surgical resection of the hyperplastic tissue to relieve urinary tract
      obstruction remains a major option for the treatment of BPH. Operations, whether
      open prostatectomy, transurethral resection of the prostate, or transurethral
      laser resection of the prostate, will inevitably affect the sexual function of
      the patient. With the increased attention to patients' quality of life, more and
      more importance is being attached to the changes in post-BPH sexual function.
      This review covers the sexual function changes induced by different surgical
      methods and assesses the possible risk factors of BPH surgery.

PMID- 21961251
TI  - [Update of PDE5 inhibitors for the treatment of ischemia-reperfusion].
AB  - Phosphodiesterase type 5 (PDE5) inhibitors are used most commonly in the
      treatment of penile erectile dysfunction (ED). Recent studies show that PDE5
      inhibitors are ideal drugs for treating ischemia-reperfusion injury. This review
      focuses on the results of basic and clinical researches on PDE5 inhibitors for
      the treatment of ischemia-reperfusion injury and provides some theoretical
      evidence for clinical options of the drugs.

PMID- 21961252
TI  - [Psychosomatic treatment: a key to the improvement of erectile dysfunction].
AB  - Erectile dysfunction (ED) has been widely accepted as a typical psychosomatic
      disorder. Psychosocial factors play a critical role in the pathogenesis of ED. In
      turn, ED also has a substantial effect on psychosocial health and interpersonal
      relationship between ED patients and their partners. It is rational that
      psychosomatic treatment is the key to the treatment of ED, including both
      psychosexual counseling and appropriate medical intervention. The evolution of
      human health mode has revolutionized the goal of ED management, focusing on the
      successful restoration of natural harmonious sexual life and intimate
      relationship between the patients and their partners, rather than the
      physiological outcomes of erection hardness and duration of maintenance.
      Tadalafil, a novel phosphodiesterase type 5 (PDE5) inhibitory agent effective for
      ED of any etiology and severity, can significantly decrease the time concerns of
      the patients, greatly satisfy the treatment expectations of both the patients and
      their partners, restore the normal and natural sexual life, and improve the
      patients' psychosexual health.

PMID- 21961253
TI  - Taking patient advocacy to a whole new level.

PMID- 21961254
TI  - CIOs report on one of their busiest years: Healthcare CIOs have their hands full
      with meaningful-use missions and other priorities. But their pockets are fuller,
      too, with a growing compensation and healthy bonuses.

PMID- 21961255
TI  - Grassroots approach builds connected health community: physician retention,
      practice survival, quality of care fuel decision.

PMID- 21961256
TI  - RHIO stabilizes finances: Rochester RHIO committee develops revenue plan to cover
      $3 million annual operating cost.

PMID- 21961257
TI  - HIE: the interoperable way to deliver quality healthcare: Finally, the concept of
      health information exchange is being more concretely defined and accepted by the
      healthcare community.

PMID- 21961258
TI  - Roadmap of a successful local HIE: The Massachusetts eHealth Collaborative
      provides an instructive success story.

PMID- 21961259
TI  - Supporting ACOs. A flexible strategy for expanding health information exchange.

PMID- 21961260
TI  - Making best use of unique device identification: UDI is valuable when it provides
      actionable intelligence to deal with critical changes in device status.

PMID- 21961261
TI  - Is your practice management system ready? HIPAA 5010 and ICD-10 have implications
      for virtually every PM system.

PMID- 21961262
TI  - Preventing network breaches: trusted platform modules are the key.

PMID- 21961263
TI  - [Surgical treatment of the spastic hip luxation at patients with severe form of
      CP].
AB  - BACKGROUND: The aim of our study was the assessment the final results of the
      operative treatment of the luxated neurogenic hips at patients with severe form
      of CP. MATERIALS AND METHODS: Analysis was performed on 13 CP patients with
      hemiplegia bilateralis treated in our department because of the neurogenic hip
      dislocation. At 5 patients (7 hips) was performed resection of femoral head
      according to Castle. At 9 patients (13 hips) the femoral osteotomy according to
      Schanz were done. The follow up ranged from 1 to 3 years. The early and late
      complications such as pain before and after surgery and nursing possibilities
      were analysed. The 4 questions concerned on the status before and after surgery.
      They assessed the pain, possibilities of crotch nursing and rehabilitation as
      well as total opinion about the final result of surgery. RESULTS: At the group of
      patients after the resection of the femoral head two of them had no pain, one
      patients complained on the decreasing pain, and two hadn't any changes. Only
      three parents assessed the surgery as satisfactory. At the group after osteotomy
      according to Schanz six patients observed no pain, two complained on the
      decreasing pain and one didn't observe any changes. The possibilities of nursing
      improved at all patients in this group. Eight parents were satisfied and one
      dissatisfied after surgery. As late complications we have classified the
      following: ossification around the hip joint in one case and destabilization of
      the plate in one another. CONCLUSIONS: The Schanz osteotomy permitted us to
      achieve the improvement in abduction of the hips at majority of the patients, the
      reduction of the pain and improvement in rehabilitation's possibilities. In our
      experience this method was more effective in the treatment of the luxated hips at
      patients with severe form of CP.

PMID- 21961264
TI  - [Total hip replacement after Legg-Calve-Perthes disease].
AB  - BACKGROUND: Total hip replacement (THR) is at present an accepted treatment in
      patients with severe osteoarthritis of the hip after Perthes disease. The aim of
      this paper is to evaluate the results of THR in patients suffering from secondary
      osteoarthritis, operated from 1990 to 2000 in the Orthopaedic and Traumatologic
      Department of Poznan University of Medical Sciences. MATERIAL: Material included
      9 patients, 3 females and 6 males, on whom 9 THR were performed, lateral approach
      was used in all cases. At the time of operation, the age of patients ranged from
      41 to 69 years (mean 56). Follow-up ranged from 11 to 21 years (mean 15 years).
      Cemented total hip arthroplasty was used during 3 of the THR, 6 of them were
      cementless. METHOD: The patients were clinically and radiologically evaluated
      preoperatively, postoperatively, and at final examination. The clinical state was
      evaluated with Harris hip score and WOMAC scale. We based our radiological
      examination on Hip Society system. RESULTS: The average preoperative Harris score
      for the group of patients was 34, WOMAC score 77. After an average of 15-years
      follow-up all hips were considered excellent, with average Harris score of 93,
      WOMAC Score of 6. All patients had increased function and decreased pain. The
      radiograms of all patients revealed that the acetabular and femoral components
      were correctly positioned with no radiographic evidence of loosening in the last
      examination. The inclination angle of the acetabular component was 22-45 degrees
      (mean: 33 degrees) and the acetabular opening angle was 0-15 degrees (mean: 3
      degrees). The stem was neutral-oriented in all hips. No ectopic ossification
      concentrations were found. CONCLUSION: Clinical and radiological evaluation of
      our material showed that total hip replacement in the treatment of osteoarthritis
      secondary to Perthes disease allows regaining good lower limb function, which
      helps the patients staying less dependant on the surrounding environment. The
      results of THR are good regardless of the type of prosthesis and the type of
      fixation. Importantly, THR was carried out after a quite long time after Perthes
      disease in the childhood.

PMID- 21961265
TI  - [Ischial tuberosity fractures in children].
AB  - BACKGROUND: Ischial tuberosity fractures in children are a form of avulsion
      fractures caused by the strong thigh muscles of the back group (ischiotibial
      muscles). OBJECTIVE: Presentation of observations covering the diagnostic
      difficulties, treatment and follow-up of ischial tuberosity fractures in
      children. MATERIAL AND METHODS: 6 children (one girl and five boys), average age
      at the time of injury - 13.6 years (12-15.5 years). An analysis of medical and
      radiological documentation of patients. RESULTS: Two patients with chronic pain
      were suspected of ischial bone tumor, one was suspected of Perthes disease, and
      only 3 were sent to the Traumatology Department immediately after the football
      injury. All patients were treated conservatively. Complete healing of fractures
      was finally achieved in all patients - (fibrous union in two cases) and finally,
      after an average period of 9 months, the pain subsided. CONCLUSIONS: There is a
      discussion in medical literature about the difficulties in the diagnosis of
      ischial tuberosity fractures, which were primarily unrecognized. Radiological
      picture of significant bone rebuilding may suggest neoplastic lesions. In the
      literature dominates the attitude of conservative treatment. Only in cases of
      large displacement of fracture and chronic ailments caused by pressure on the
      sciatic nerve, surgery should be considered.

PMID- 21961266
TI  - [Spinal pain syndromes and constitutional hypermobility].
AB  - INTRODUCTION: The most common cause of spinal pain syndromes (SPS) is overload of
      the spine. It damages the function of the spine and the morphology of the spine's
      tissues. The literature suggests that a generalized insufficiency of connective
      tissue, which manifests itself as a hypermobility of joints (JHM), might be one
      of the causes of overload. The authors decided to evaluate, whether a frequency
      of the prevalence of JHM is greater within the population of patients treated
      because of spinal pain syndromes, and whether JHM might be a pathogenetical
      factor in sps. MATERIAL AND METHOD: The material consisted of 8014 case records
      of patients treated in Rehabilitation Clinic because of dysfunctions and diseases
      of locomotoric system during 7 years. 7061 of those patients were treated for
      sps. The control group consisted of 953 patients without SPS, treated because of
      other reasons. All patients underwent an examination to screen for hypermobility.
      Four simple maneuvers of the peripheral joints and joints of the spine were
      performed. If hypermobility of joints was detected during testing, the patient
      underwent a complete examination of 13 tests using the Sasche criteria modified
      by Kapandij and was interviewed to screen for accompanying symptoms of
      hypermobility. RESULTS AND CONCLUSIONS: Hypermobility syndrome is recognized much
      more often in patients with spinal pain syndromes, than in patients treated
      because of other diseases (7.9% i 0.7%) and twice more often in females than in
      males (69.7% i 30.3%). Among young people, under 30 years of age hypermobility
      occurs in 55% of population with SPS. In the youngest patients HMS may be the
      cause of overload spinal pain syndromes, and a predisposition factor towards
      spinal pain syndromes in older patients.

PMID- 21961267
TI  - [The influence of segmental stabilization training upon the reduction of motor
      system weak connections in hockey players].
AB  - AIM: Two hypothesis were lunched: 1) three month segmental stabilization training
      (TSS) has the influence on reducing the number of weak connections in
      biokinematics chain in hockey players; 2) three month training has influence on
      reducing the pain perception in low back of a spine (LBP) in players. This work
      has been undertaken to estimate the usefulness of the low Performance Matrix
      threshold tests.Furthermore, the correlationbetween segmental stabilization
      training and the number of weak connections in biokinematics chain in hockey
      players has been tested. MATERIALS AND METHODS: 12 players-hockey champions of
      Poland and vice-champions of Europe took part in the conducted research. An
      average age of a group is 30 +/- 5.03 years, an average training period 20.83 +/-
      5.65 months. The low Performance Matrix threshold tests were used for weak
      connection assessment. Through analysis and identification of a performed motion
      the weakest connections of biokinematics chain have been found. The test were
      undertaken at the beginning of the research and it was repeated after 3 month.
      The players were advised to continue the segmental stabilization training for 3
      months. Assessment of Low Back Pain (LBP) was undertaken by using the numerical
      scale. LBP was tested at the beginning of the project and after 3 months. The
      results were tested by using statistic analysis. RESULTS: For obtained weak links
      based statistical characteristics were gained before and after the TSS training.
      Two hypothesis have been tested: the first is about variance equality, the second
      has been settled to confirm that weak links before TSS training have the bigger
      values than weak links after TSS training. Next the correlation between weak
      connections before TSS training and after TSS training was determined. Variance
      analysis was done for regression. CONCLUSIONS: 1) Three month segmental
      stabilization training (TSS) has the influence on reducing the number weak
      connections in biokinematics chain in hockey players. 2) Three month training has
      influence on reducing the pain perception in lower back of a spine (LBP) in
      players. 3) Performance Matrix low threshold tests have occurred to be a
      diagnostic tool due to which the quality of motor control can be assessed
      successfully in hockey players. 4) The correlation between segmental
      stabilization training and reducing of motor system's weak connection was found
      for hockey players.

PMID- 21961268
TI  - [Surgical treatment of pertrochanteric femoral benign tumors in children].
AB  - INTRODUCTION: Disclosure of the tumor area intertrochanteric femur occurs mostly
      at the time of pathological fracture. Detection of changes can also be made in
      conjunction with x-ray of the hip joint such as the hip injury. The purpose of
      this study was to present the treatment of benign tumors of the intertrochanteric
      area in children and adolescents. MATERIALS AND METHODS: From 1. 01. 2002 to 31.
      12. 2009 13 patients were treated with benign tumors of the femur
      intertrochanteric area, including 10 with pathological fractures in the
      background. Average age was 9.8 years (5-13 years). There were 11 boys and 2
      girls. The procedure was performed with resection of the tumor,histopathology,
      allogenic bone grafting, the femur was fixed using locked plate (10 patients) or
      angular plate (3 patients). RESULTS: The mean observation time was 62 months (24
      94 months). Histopathology examination showed a simple cyst in 7 patients,
      aneurysmal cyst in 2 patients, and fibrous dysplasia of bone in 4 patients. Bone
      consolidation was achieved in 10 patients after an average of 4 months (3-5
      months) after surgery, as determined by X-ray examination and clinical
      examination. In 3 cases there was a recurrence of the tumor, 2 patients with
      fibrous dysplasia after 4 months and 6 months after surgery were found in X-ray
      partial resorption of bone graft >25%, and 1 patient after 4 months presented
      fatigue fracture at Adams angle. After re-treatment complete bone consolidation
      was achieved in this group after an average of 4 months (2.5-5 months) from the
      second surgery. 1 patient with aneurysmal cyst in 11 month after surgery,
      presented femoral infection, sequestrum and plate were surgically removed,
      antibiotic therapy was used and the inflammatory process was stopped. CONCLUSION:
      Surgical treatment of benign tumors of the intertrochanteric area of the femur
      gives good results if it is carried out by a complex surgery (resection of the
      tumor - bone graft - osteosynthesis).

PMID- 21961269
TI  - [Application of negative-pressure wound therapy in complex therapy of open tibia
      fractures IIIB and IIIC with massive soft tissue loss].
AB  - Patients with high-grade open tibia fractures and massive soft tissue damage pose
      a demanding clinical challenge, requiring a complex inter-disciplinary approach
      and multiple orthopedic, vascular and plastic-reconstructive procedures. These
      types of fractures still have a 50% risk of loss, although amputation remains a
      treatment method of last resort. In our experience negative-pressure wound
      therapy (NPWT), used in the form of the vacuum assisted closure - VAC System
      (KCI, USA) improves healing of excessive soft tissue damage with exposure of the
      bone accompanying open fracture of the tibia. VAC seals the wound with a foam
      dressing and applies negative pressure to the wound bed. The removal of exudate
      and infectious material supports the cleaning of the wound. Together with the
      reduction of oedema and the increase in blood flow, this promotes formation of
      granulation tissue and eventually wound closure by split skin graft. Utilizing
      this method as part of a multi directional approach VAC System not only helps the
      patient to recover faster but also in some cases can replace microsurgical soft
      tissue transfer and thus allows salvage of the leg in orthopaedic teams lacking
      advanced reconstructive experience.

PMID- 21961270
TI  - [Clinical and metallographic evaluation of the causes of mechanical loosening of
      revision baskets Recon Ring--description of 3 cases].
AB  - Aim of this study is to assess the causes of mechanical loosening of revision
      Recon Ring baskets (Aesculap / BBrown, Germany). This analysis was done by
      assessing the circumstances of baskets loosening of revision in 3 patients.
      Intraoperative images and radiographs of patients with these clinical
      complications were analyzed, and removed damaged bins and bolts of revision
      metallographic expertise. It was found that the most likely cause mechanical
      damage to the implant was originally unstable or re-fixing their ischial part,
      causing movable canopy closer to the basket is balanced by the screws and in turn
      causing fracture or bending arms, and follow-up baskets of hip bone loss. Our
      observations suggest that the most important is proper attachment of acetabular
      basket, especially his arm sciatic.

PMID- 21961271
TI  - [Differential diagnosis of certain knee joint tumours and casuistry].
AB  - The subject of this information is the case of 33-year old male patient with
      tumefactive lesions of knee joint. It became an inspiration for this study due to
      diagnostic difficulties. The article covers the differential diagnosis of such
      pathologies as: synovial sarcoma, chondromatosis, tuberculosis and knee joint
      synovitis.

PMID- 21961272
TI  - [Possibilities of leg length equalization in total hip replacement].
AB  - Leg length discrepancy is a common and not appreciated complication after THR.
      Unequal leg length may cause earlier implant wear, patient's dissatisfaction,
      impair patient's function or even some legal consequences for the surgeon. To
      achieve the final equal leg length after surgery one must comply with some rules:
      proper patient's examination, informing patient about possible leg length
      discrepancy, proper length measurement- both clinical and radiological after
      antero-posterior pelvis x-ray; proper radiological length measurements especially
      when some hip contractures are observed, appropriate implant selection, proper
      prosthesis templating. The intraoperative leg length measurement with some
      surgical or radiological devices is essential for leg equalization. Special
      operative techniques are necessary for leg lengthening or shortening without hip
      instability. Final leg length measurement after surgery is necessary to determine
      a rehabilitation program.

PMID- 21961273
TI  - [Scapholunate instability of the wrist--a review].
AB  - Injury to the scapholunate ligament is considered the most common and burdened
      with the most negative squeals cause of the carpal instability. The article
      provides information on the functional anatomy of the scapholunate complex and
      the consequences of the tear of the ligament that joints these bones. Rupture of
      this ligament, associated with tear of extrinsic (secondary) stabilizers of the
      wrist leads on to dislocation of the carpal bones one against another and,
      finally, results in carpal instability. Classifications of the severity of the
      instability based on radiological and arthroscopic grounds were presented.
      Clinical symptoms and signs of the condition were described as well as imaging
      techniques helpful in its diagnosing. The usefulness of arthroscopy was
      emphasised in diagnosing of scapholunate complex disturbances, particularly those
      which are negative radiologically and present with no typical symptoms.

PMID- 21961274
TI  - [Clinical outcome in prostate cancer patients undergoing high-dose-rate
      brachytherapy with external beam radiotherapy in our institute].
AB  - OBJECTIVES: We investigate the biochemical control rates and adverse events for
      local and locally advanced prostate cancer patients undergoing high-dose-rate
      brachytherapy with external beam radiotherapy (EBRT + HDR-BT) in our institute.
      PATIENTS AND METHODS: From May 2004 through March 2010, 154 patients with local
      and locally advanced prostate cancer underwent EBRT + HDR-BT. One hundred
      thirteen patients with more than 6 months follow-up were evaluated. A median
      follow-up was 33 months. The patients consisted of 12 low-, 65 intermediate- and
      36 high-risk patients. No patients received adjuvant androgen deprivation therapy
      with EBRT + HDR-BT. Biochemical freedom from failure (bFFF) was determined using
      the Phoenix definition. RESULTS: The 5-year bFFF rate was 100%, 94.7%, and 59.2%
      for low-, intermediate- and high-risk patients. The 58-month bFFF rate of high
      risk patients with one ominous factor was significantly lower than that of high
      risk patients with more than ominous two factors (87.4% vs 26.9%, p = 0.022).
      With respect to acute adverse events, transurethral electric coagulation was
      performed for vesical bleeding and tamponade after removal of applicator needles
      in only one patient. Regarding late adverse events 14.2% of patients had grade 3
      genitourinary toxicity, mostly consisted of urethral stricture and 0.9% of
      patients had grade 3 gastrointestinal toxicity. CONCLUSIONS: EBRT + HDR-BT
      without adjuvant androgen deprivation therapy yields excellent bFFF in low- and
      intermediate-risk prostate cancer patients. However, to challenge higher bFFF
      rate in a part of high-risk patients and lower rate of adverse events, modified
      designing protocols and therapeutic plannning of EBRT + HDR-BT may be necessary.

PMID- 21961275
TI  - [Clinicopathological study of retroperitoneal sarcoma].
AB  - OBJECTIVES: The purpose of this study was to retrospectively analyze the
      characteristics of patients with retroperitoneal sarcoma and to examine
      pathological findings, first site of recurrence and recurrence free-survival
      after surgery. METHODS: From June 2003 to May 2010, we performed 10 surgeries for
      retroperitoneal sarcomas. We chose 9 tumors after excluding 1 tumor that had
      already disseminated in the abdominal cavity. We examined patient
      characteristics, pathological findings and the first site of recurrence (local or
      distant metastasis). We also analyzed recurrence-free survival after surgery with
      the Kaplan-Meier method. RESULTS: The patients' median age was 60 years (31-71
      years), and the median tumor diameter was 10.0 cm (2.7-45 cm). Pathological
      diagnosis revealed 7 cases of dedifferentiated liposarcoma and 2 cases of
      leiomyosarcoma. En-block resection with adjacent organs was achieved in 8 of 9
      patients. During follow-up, 5 of 9 patients experienced tumor local recurrence.
      There were no cases in which distant metastases appeared before local recurrence.
      The median duration between surgery and local recurrence was 13 months (3-27
      months). The median duration from surgery to death was 30 months (5-78 months).
      CONCLUSIONS: Although we resected adjacent organs together when we could not
      achieve a sufficient margin, the rate of local recurrence after surgery for
      retroperitoneal sarcoma was high. Given this result using treatment with surgery
      alone, it is necessary to prospectively establish multimodal treatments with
      chemotherapy and radiotherapy to reduce local tumor recurrence.

PMID- 21961276
TI  - [A case report of ureteropelvic junction obstruction and multiple renal stones
      associated with nutcracker syndrome].
AB  - A 20 year-old man presented to emergency room with severe left-sided flank pain.
      Urinalysis showed hematuria and he was referred to the urology department. KUB,
      DIP and retrograde pyelography (RP) revealed multiple renal stones, left
      hydronephrosis (grade 2) and ureteropelvic junction obstruction (UPJO). Abdominal
      CT revealed shortened nutcracker distance and renal angiography showed left renal
      vein hypertension. From these findings, diagnosis of nutcracker syndrome was
      made. Transposition of the left renal vein, dismembered pyeloplasty and left
      pyelolithotomy were performed simultaneously. 2 months after the procedure, his
      symptom and hematuria disappeared. 3 months after the procedure, DIP revealed
      improvement of hydronephrosis (grade 1) and CT showed elongation of nutcracker
      distance. In 12 months follow-up, there was no recurrence of symptom and
      hydonephrosis. To the best our knowledge, there has been no report of UPJO
      associated with nutcracker syndrome and the simultaneous treatment for the both
      diseases.

PMID- 21961277
TI  - [Successful treatment with multidisciplinary therapy including low-dose
      chemoradiotherapy against metastatic recurrences of small cell carcinoma of the
      renal pelvis: a case report].
AB  - Primary small cell carcinoma of the renal pelvis is a rare and aggressive
      disease; reportedly, a mean survival is only 8 months. A 78 year-old woman with
      chronic kidney disease was referred to our hospital complaining of asymptomatic
      gross hematoturia. On imaging studies and voided urine cytology, diagnosis of
      right renal pelvic cancer (cT2N0M0) was made. She underwent total
      nephroureterectomy. Pathological diagnosis was small cell carcinoma, infiltrating
      into the renal parenchyma, with lymphovascular invasion. Post-operatively,
      hemodialysis was introduced. Five months after the operation, new lesions
      developed in the right adrenal gland, aortocaval lymph nodes and subcutaneous
      layer of the right back. The subcutaneous mass was surgically removed and low
      dose chemoradiotherapy (sigma 45 Gy/25 Fr/32 d + cisplatin 10 mg/d for 2 d x 2)
      was given to the other lesions. Although the lesions regressed to CR, new small
      masses emerged in the muscle layers of the right flank 14 months after total
      nephroureterectomy. Low-dose chemoradiotherapy (sigma 40 Gy/20 Fr/29 d +
      cisplatin 10 mg/d for 2 d x 2) to these lesions successfully brought CR. She is
      alive without any evidence of disease at 3 years after total nephroureterectomy.

PMID- 21961278
TI  - [Group a streptococcal necrotizing fasciitis of the genital area (Fournier's
      gangrene): a case report].
AB  - A necrotizing fasciitis especially caused by group A streptococcal infection is a
      life-threatening disease. This infection cause death due to septic shock and
      multiple organ failure in a short time without the immediate and adequate
      treatment. Currently a rapid test kit for streptococcal pharyngitis (strep A) is
      useful for prediction of group A streptococcal infection. We here demonstrate a
      61 years old man's case of life-saved necrotizing fasciitis in genital area
      (Fournier's gangrene) by group A streptococcus infection, and usefulness of this
      kit for rapid diagnosis, aggressive debridement, and selection of adequate
      antibiotics.

PMID- 21961279
TI  - [A case of Fournier's gangrene reconstructed using a rectus abdominis muscle
      flap].
AB  - We encountered a case of Fournier's gangrene complicated with
      vesicorectocutaneous fistula that was treated with a pedicled rectus abdominis
      muscle flap (pedicled RA m-c flap). A 75-year-old man was admitted with
      consciousness disorder and swelling of the scrotum. The patient had noticed
      swelling of the scrotum 4 days before admission, but he had ignored this
      condition. The scrotum and the penis appeared necrotic. On the basis of clinical
      and radiological findings, we diagnosed this condition as Fournier's gangrene.
      Surgical debridement was performed in conjunction with the use of broad-spectrum
      antibiotics. After the patient's general condition was improved, the broad defect
      in the perineal tissue was covered with a pedicled rectus abdominis muscle flap.
      The flap was successful. In Japan, this is the first case of Fournier's gangrene
      complicated with vesicorectocutaneous fistula that was treated with a pedicled RA
      m-c flap. In order to determine whether plastic surgery after debridement
      shortens the duration of hospitalization, we reviewed the cases of 120 patients
      with Fournier's gangrene in Japan. We conclude that plastic surgery after
      debridement does not shorten the duration of hospitalization, however, this
      procedures is very useful to deep and broad defects by Fournier's gangrene.

PMID- 21961280
TI  - [Acute abducens nerve palsy following prostatitis due to prostate biopsy].
AB  - This is a case of repeated acute abducens nerve palsy following prostatitis due
      to prostate biopsy. A 64-year-old man came to our hospital because of high
      prostate specific antigen (PSA; 25 ng/ml) on routine medical examination.
      Transrectal prostate needle biopsy revealed atypical small acinar proliferations
      in two cores taken from the apex of the prostate. One day after biopsy, the
      patient presented with chills and a fever. Prostatitis due to prostate biopsy was
      diagnosed, and hydration and intravenous antibiotics were administered. Although
      he showed signs of improvement, seven days after biopsy, he complained of double
      vision in the left gaze. Upon referral to the neurology, head MRI and CSF
      examination showed no particular abnormality. He was thus diagnosed with post
      infection abducens nerve palsy and treated with steroid therapy. His symptoms
      gradually ameliorated. One year after biopsy, his PSA level was still high,
      although follow-up prostate biopsy was benign. One day after follow-up biopsy, he
      presented again with chills and a fever. He was retreated with hydration and
      intravenous antibiotics. Six days after follow-up biopsy, he complained of double
      vision in the left gaze as in the previous year. With the diagnosis of post
      infection abducens nerve palsy, he was retreated with steroid therapy.

PMID- 21961281
TI  - [cAMP, cGMP and their visualization in living cells using fluorescent
      microscopy].
AB  - cAMP and cGMP are ubiquitous second messengers regulating a myriad of
      intracellular functions. Standard biochemical techniques to measure their levels
      in cells and tissues lack high temporal and any spatial resolution. To enable
      real-time monitoring of cAMP and cGMP in living cells and physiological systems,
      we and others have developed several biosensors based on fluorescence resonance
      energy transfer. This review will describe such novel techniques and discuss
      their application for various biological questions.

PMID- 21961282
TI  - [Using peptide strategy for study functions and structure of signal proteins with
      enzymatic activity].
AB  - The peptide strategy, a new direction of molecular endocrinology, includes the
      synthesis of peptides corresponding to functional regions of signal proteins, the
      use of the peptides for study of the molecular mechanisms of transduction of
      hormonal signal into cell ant the development of selective regulators of hormonal
      signaling systems on the basis of these peptides. The peptide strategy is used
      for study a wide spectrum of the proteins, components of signal systems, the
      proteins possessing the catalytic activity in particular, such as tyrosine
      kinases receptors, the enzymes generating the second messengers, serine/threonine
      protein kinase, phosphatases. In the first time in the review the data concerning
      the synthetic peptides, derivatives of the primary structure of proteins with the
      enzymatic activity, their application for study of the structural-functional
      organization and the molecular mechanisms of action of signal proteins, and the
      construction of regulators of fundamental cell processes on the basis of these
      peptides are analyzed and summarized.

PMID- 21961283
TI  - [The surface expression of CD25 at different stages of proliferative response in
      human lymphocytes. I. The role of JAK and Src tyrosine kinases as revealed by
      inhibitory analysis].
AB  - The long-lasting expression of an alpha-subunit of interleukin-3 receptor (IL
      2Ralpha) was found to accompany the PHA-induced proliferation of human blood
      lymphocytes (HBL), so that to the end of the second day of mitogenic stimulation
      only, the large blasts may express the high affinity alphabetagamma(c) receptor
      for IL-2. With the selective pharmacological drugs to JAK (WHI-P131) and Src
      (PP2) it is shown that the non-receptor tyrosine kinases are involved in the
      surface CD25 expression. It is revealed that the PP-2-inhibitable expression of
      CD25 is timely associated with the initial stage of T cell activation, whereas
      WHI-P131-inhibitable expression was present during the whole G0/G1/S transition.
      These data indicate that at the early, antigen-dependent stage the expression of
      IL-2Ralpha is induced via Src-dependent signaling pathway, and prolonged increase
      in IL-2Ralpha expression is regulated by IL-2/IL-2 receptor interaction via JAK
      dependent signaling pathway.

PMID- 21961284
TI  - [The surface expression of CD25 at different stages of proliferative response in
      human lymphocytes. II. The role of interleukin-2].
AB  - The expression of alpha-subunit of interleukin-2 receptor (IL-2Ralpha) was
      assessed by quantifying activation-induced upregulation of CD25 in human blood
      lymphocytes (HBL) stimulated by interleukin-2 (IL-2). It was established that
      exogenous IL-2 induced no surface expression of CD25 neither proliferation at 48
      h of IL-2 action. In component HBL, pretreated by sub-mitogenic doses of
      phytohemagglutinin (PHA), 5-15 % of cell population was revealed to represent the
      CD2t+ cells, and in the competent cells only, exogenous IL-2 induced the surface
      expression of CD25 as well as the growth and the proliferative response, which
      was comparable with those to mitogenic doses of PHA. The JAK3 inhibitor WHI-P131
      eliminated IL-2-dependent CD25 expression without influencing the CD25 expression
      in competent cells. Unlike, PP2 was found to inhibit the IL-2-dependent CD25
      expression in a lesser extent than WHI-P131, however this drug was effectively
      inhibited CD25 expression in PHA-pretreated, competent HBL. These data suggest
      that Src-dependent signaling participate in the early IL-2Ralpha expression that
      precedes the IL-2-dependent cell cycle progression of activated HBL. It is
      concluded that in normal T cells, the IL-2Ralpha expression in firstly induced by
      antigen (mitogen) and thereafter it is held IL-2 through JAK-dependent signaling
      pathway.

PMID- 21961285
TI  - [The effect of retinoic acid on the meiosis in the chick embryo (Gallus gallus
      domesticus)].
AB  - In this study it was shown that the injection of retinoic acid (RA) into
      incubated eggs on day 9 or 14 induced entry the males germ cells into
      preleptotene stage of prophase I on day 17, which are absent in the control
      embryos. At the same time the meiosis marker SCP3 was detected in the germ cells.
      Which was also absent at control embryos. On day 19 in male embryos the number of
      male germ cells at the stage preleptoteny increased, but there were no germ cells
      in the following stages of the prophase of meiosis. In 20-day-old chicks meiotic
      germ cells were absent. Thus, white it is shown that the influence of RA on the
      developing chicken embryos induces the entry of germ cells into preleptotene
      stage of prophase I meiosis. However, further meiotic transformations don't
      occur. Thus RA is only one of many factors providing meiotic cell division.

PMID- 21961286
TI  - [Cystathionine beta-synthase in the structural elements of the human brain and
      spinal cord].
AB  - Investigated by immunohistochemistry the presence and distribution of CBS in the
      nuclei of the spinal cord and brainstem in 8 mens of 18-44 years old, died from
      mechanical injury is not related to the central nervous system damage.
      Established that the CBS-neurons are revealed in all parts of stem and spinal
      cord, but their content in the studied cores, ranging from 0.9 to 17 %. Observed
      a definite relationship between the activity of CBS and the quantity of neurons.
      Large cells of motor nuclei often have a high and very high intensity of the
      reaction. In the sensory nuclei of a high proportion of small neurons with low
      activity of the enzyme.

PMID- 21961287
TI  - [The average cell size as a factor reflecting the interaction of the CHO cells
      during process of proliferation].
AB  - Changes in the cell area during cultivation of the CHO line cells were studied
      using time-lapse technique (start of registration in one day after cell plating).
      It was established that the size of the daughter cells after mitosis remains lees
      than the size of the mother cell for a long time (up to 6 h). Nevertheless, the
      average cell area of the whole population is constant throughout the observation
      period (up to 18 h). We assume that this phenomenon could be a result of
      interaction among dividing and not-dividing cells. The experimental data
      confirming this conclusion are presented.

PMID- 21961288
TI  - [Role of protein kinases in prolactin signaling in bovine oocyte-cumulus
      complexes].
AB  - Mechanisms of prolactin signal transduction in generative and somatic cells of
      mammalian ovarian follicles have been studied only to a small extent. In the
      present work, the involvement oftyrosine kinases and protein kinase C in
      mediating of the previously revealed modulating effects of prolactin on the
      nuclear maturation of bovine oocytes and the morphologic-functional state of
      surrounding cumulus cells was investigated in vitro. Tyrosine kinase inhibitor,
      genistein, was found to suppress the stimulating action of prolactin on the
      completion of oocyte nuclear maturation and cumulus expansion, whereas protein
      kinase C inhibitor, calpostin C, did not affect these hormonal effects.
      Furthermore, both genistein and calpostin C inhibited the inducing influence of
      prolactin on the proliferative activity of cumulus cells. At the same time the
      retarding action ofprolactin on destructive processes in cumulus cells was
      blocked only in the presence of calpostin C. The results of the study suggest
      that the stimulatory influence of prolactin on oocyte nuclear maturation and
      attendant cumulus expansion is achieved with the participation of tyrosine
      kinases, whereas the modulating action of the hormone on the functional state of
      cumulus cells depends on activation of not only tyrosine kinases, but also
      protein kinase C.

PMID- 21961289
TI  - [On the theory of apoptotic decrease of the cell volume].
AB  - The dynamic model of membrane transport, which describes the changing of ion
      contents in the cell, cell volume and membrane potential, for the first time, is
      applied to analysis of the apoptotic processes. It is shown that increasing of
      permeability of K+, and Cl(-)-channels, decreasing of permeability of Na+
      together with degradation of Na+/K+ pump, KCC and NC cotransporters lead to
      decreasing of cell U937 volume and plasma membrane depolarization at apoptosis
      induced by staurosporine in concentration 1 microM. The experimental data using
      at calculations was published in paper (Yurinskaya et al., 2010).

PMID- 21961290
TI  - [Content of chaperon Hsp70 in dopaminergic neurons of the black substance
      increases in proteasome dysfunstion].
AB  - In Wistar rats, specific inhibitor UPS lactacystin induced degeneration of 24% of
      the dopaminergic neurons in the black substance. The work shows that a moderate
      weakening of the UPS function is characterized by an enhanced activity of the
      shaperon system. This process seems to restore and maintain population of the
      dopaminergic neurons.

PMID- 21961291
TI  - Interactions of drugs and toxins with permeant ions in potassium, sodium, and
      calcium channels.
AB  - Ion channels in cell membranes are targets for a multitude of ligands including
      naturally occurring toxins, illicit drugs, and medications used to manage pain
      and treat cardiovascular, neurological, autoimmune, and other health disorders.
      In the past decade, the x-ray crystallography revealed 3D structures of several
      ion channels in their open, closed, and inactivated states, shedding light on
      mechanisms of channel gating, ion permeation and selectivity. However, atomistic
      mechanisms of the channel modulation by ligands are poorly understood. Increasing
      evidence suggest that cationophilic groups in ion channels and in some ligands
      may simultaneously coordinate permeant cations, which form indispensible (but
      underappreciated) components of respective receptors. This review describes
      ternary ligand-metal-channel complexes predicted by means of computer-based
      molecular modeling. The models rationalize a large body of experimental data
      including paradoxes in structure-activity relationships, effects of mutations on
      the ligand action, sensitivity of the ligand action to the nature of current
      carrying cations, and action of ligands that bind in the ion-permeation pathway
      but increase rather than decrease the current. Recent mutational and ligand
      binding experiments designed to test the models have confirmed the ternary
      complex concept providing new knowledge on physiological roles of metal ions and
      atomistic mechanisms of action of ion channel ligands.

PMID- 21961292
TI  - [The effect of insulin on circadian rhythm of voluntary locomotor activity in
      rats].
AB  - Effects of single intranasal administration of 0.2 ng insulin at different
      moments of the projected daily cycle (ZT = 1, ZT = 7, ZT = 13 and ZT = 19) on the
      circadian rhythms of voluntary locomotor activity (wheel-running) were studied in
      Wistar male rats. Insulin administered at ZT-7 or ZT-13 induced a statistically
      significant phase advance by 4.4 and 5.5 hours, respectively. The administration
      of insulin at ZT-13 additionally induced a reduction of the period of the
      circadian rhythm of voluntary locomotor activity. Intranasal administration of
      insulin at other moments of the projected daily cycle (ZT = 1 or ZT = 19) did not
      induce any statistically significant change in phase or period duration of the
      circadian rhythms. Insulin did not cause changes in total daily activity
      irrespective of administration time. The results of the study suggest the role of
      endogenous insulin as entrainment factor for circadian oscillator in absence of
      the main physiological zeitgeber--cyclic afferent input from retina
      photoreceptors.

PMID- 21961293
TI  - [Effect of intranasal administration of dopamine on anxiety and locomotor
      activity of two lines of mice].
AB  - Intranasal administration of dopamine (0.3; 3 and 30 microg/kg) on anxious
      behaviour of mice was studied using elevated plus-maze and open fields tests and
      the pinch-induced catalepsy on parallel bars test. Dopamine was introduced as
      nose drops or inhalation of nanoparticles of the compound solution in C57B1/6J
      and CBA/Lac mice with differences of dopaminergic function features. In our
      experiment, dopamine had anxiolytic and elevated motor activity effects in
      C57B1/6J, but not in the CBA/Lac mice. Nose drops were more effective than
      inhalation; perhaps, it was a more stressful manipulation. Apparently dopamine
      increased the number of CBA/Lac mice who demonstrated catalepsy and the reflex
      duration. Indeed, the neurotransmitter is active in different psycho-emotional
      phenomena.

PMID- 21961294
TI  - [Interaction of N-methyl-D-aspartate and Dopamine D1 receptors in modulation of
      passive avoidance extinction at mice with depressive-like state].
AB  - The effect of activation of N-methyl-D-aspartate (D-cycloserine) and dopamine D1
      (SKF 38393) receptors on learning and extinction of the passive avoidance
      response in mice under normal conditions and after formation of "behavioural
      despair" is studied. The data on ineffectiveness of D-cycloserine and SKF 38393
      on training a conditional reflex were obtained. In mice with the normal state,
      SKF 38393 did not alter the dynamics of extinction, and D-cycloserine facilitated
      a more rapid decline in retrieval of memory trace when testing without penalty.
      On exposure to D-cycloserine + SKF 38393 injection, dynamics of extinction was
      similar to that under the action of D-cycloserine. In mice with the reaction of
      "behavioral despair", D-cycloserine and SKF 38393 reduced the deficit of the
      passive avoidance extinction typical for "depressed" animals without drugs. With
      simultaneous activation of NMDA and D1 receptors we observed acceleration of the
      extinction start and development of complete extinction of the memory trace about
      pain impact as compared with single injections of D-cycloserine and SKF 38393.

PMID- 21961295
TI  - [Amides of creatine: perspectives of neuroprotection].
AB  - We evaluated the efficacy of derivatives of creatine and amino acids (CrAA) for
      decreasing cerebral injury in rats with transient middle cerebral artery
      occlusion (MCAO). Neuroprotective effects of amides of creatine and glycine
      (CrGlyOEt), phenylalanine (CrPheNH2), thyrosine (CrTyrNH2), and GABA (CrGABAOEt)
      were investigated. Brain injury was evaluated on day 2 after transient MCAO using
      a TTC staining of brain slices. Compared with the MCAO control group, all the
      CrAms showed decreased cerebral injury (p < 0.05). However CrPheNH2, CrTyrNH2,
      and CrGABAOEt were toxic after intravenous administration and investigated only
      after intraperitoneal injection. CrGlyOEt did not show any toxicity at dose of 1
      mmol/kg. These data evidenced that creatinyl amides can represent promising
      candidates for the development of new drugs useful in brain ischemia treatment.

PMID- 21961296
TI  - [Modification of the erythrocyte membrane lipids in rats under conditions of
      alimentary stress].
AB  - Erythrocyte phospholipids and lipid fatty acid composition was investigated at
      different stages of exposure to high-caloric diet in male Wistar rats. The
      revealed modification of erythrocyte lipids shows specific features of membrane
      response to stress factors of alimentary nature, in particular, cell protection
      compensatory mechanism initiation on the 90th day and their depletion by the
      180th day of high-caloric diet.

PMID- 21961297
TI  - [Morphofunctional and biochemical properties of erythrocytes in early postnatal
      ontogenesis in rats in norm and after prenatal stress].
AB  - Morphofunctional and biochemical properties of erythrocyte membrane were
      investigated in early postnatal ontogenesis in rats in norm and after prenatal
      immobilization stress. The transient decrease of erythrocyte membranes stability
      was revealed in the control rats. The ability to erythrocyte transformation and
      the concentration of lipid peroxidation products are increased. It has been shown
      by an increase of percentage discocytes and lower lipid peroxidation level that
      the erythrocyte membrane of the rats after prenatal stress is more stable.

PMID- 21961298
TI  - [Blood flow in skeletal muscles of chicken in the embryonic and early
      postembryonic periods].
AB  - In chicken Leghorn, blood flow volume speed in pectoralis and gastrocnemius
      muscles was measured on 15 and 19 day-old embryos and at the 1st and the 10th
      days alter hatching. It was revealed that in the last quarter of embryogenesis BF
      in muscles did not vary remaining in both muscles in identical limits. Similar BF
      parameters in pectoralis and gastrocnemius muscles and their age-dependent
      dynamics were observed at embryos with the detained development (with the body
      weight 2-fold less than the norm). After hatching, the blood flow in both muscles
      was grown, on the average, 2.4-fold and remained high by the 10th day, a little
      decreasing in the pectoralis muscle. It was shown, that increase of a muscular
      blood flow after hatching was accompanied by different changes of anatomic lumen
      of the arteries addressed in pectoralis and gastrocnemius muscles: in the former
      it decreased, in the latter--increased.

PMID- 21961299
TI  - [Physiology in the mirror of systematic catalogue of Russian Academy of Sciences
      Library].
AB  - Representation of general human and animal physiology publications in the
      systematic catalogue of the Library of the Russian Academy of Sciences is
      considered. The organization of the catalogue as applied to the problems of
      physiology, built on the basis of library-bibliographic classification used in
      the Russian universal scientific libraries is described. The card files of the
      systematic catalogue of the Library contain about 8 million cards. Topics that
      reflect the problems of general physiology contain 39 headings. For the full
      range of sciences including physiology the tables of general types of divisions
      were developed. They have been marked by indexes using lower-case letters of the
      Russian alphabet. For further detalizations of these indexes decimal symbols are
      used. The indexes are attached directly to the field of knowledge index. With the
      current relatively easy availability of network resources value and relevance of
      any catalogue are reduced. However it concerns much more journal articles, rather
      than reference books, proceedings of various conferences, bibliographies,
      personalities, and especially the monographs contained in the systematic
      catalogue. The card systematic catalogue of the Library remains an important
      source of information on general physiology issues, as well as its magistral
      narrower sections.

PMID- 21961300
TI  - [I.M. Sechenov's creative development of ideas in aviation and space medicine].
AB  - Research carried outby the great Russian scholar I. M. Sechenov has significantly
      contributed to development of aviation physiology, medicine and psychology. His
      fundamental works consisted of discovery of the constancy of alveolar air
      composition theory, study of interactions of analyzers systems in solving the
      problem of human spatial orientation under flight conditions, development of a
      nervous theory of fatigue. Creative development of ideas by I. M. Sechenov
      allowed enhancing the efficiency of performing and safety of aviation and space
      flights.

PMID- 21961301
TI  - [Uncoupling proteins and their role in the regulation of brain and heart
      tolerance to impact of ischemia and reperfusion].
AB  - Experimental data indicate that moderate uncoupling oxidative phosphorylation
      induces reduction in production of reactive oxygen species (ROS) and promotes an
      increase in survival of neurons and cardiomyocytes under hypoxia and re
      oxygenation conditions. Uncoupling proteins (UCP) are expressed by cardiomyocytes
      and neurons. These proteins are involved in the thermogenesis, inhibit ROS
      generation by mitochondria, reduce deltaphi, elevate respiration rate of these
      organelles. It was established that UCP contributed to the elevation of
      cardiomyocyte and neuron tolerance of an impact of hypoxia and re-oxygenation.
      They also promote cell resistance to oxidative stress. Experimental data indicate
      the important role of the UCP in the neuroprotective and cardioprotective effects
      of ischemic preconditioning. At the same time, real contribution of the UCP in
      preconditioning is still to be verified.

PMID- 21961302
TI  - [Influence of tenotomy on posttetanic responses of the rat fast and slow muscle].
AB  - The effect of two weeks of tenotomy on posttetanic isometric contractile
      responses of the rat fast: Extensor digitorum longus and slow: soleus muscles was
      studied in experiments on isolated muscle preparations. Direct tetanic
      stimulation (100 impulses, 50 Hz) increased the force of contractions by 20-25%
      (p < 0.05) of both, control and tenotomized fast muscles. Identical to above
      tetanic stimulation of control, slow muscle resulted in posttetanic depression, a
      decrease in the amplitude of contractile responses. Tenotomized slow muscles did
      not develop posttetanic depression. Caffeine (4 mM) increased and dandrolene (10
      microM) decreased the force of unitary and tetanic contractions of control and
      tenotomized muscles. Neither drug, however, affected development of posttetanic
      phenomena in ether fast or slow muscles. The fact that in extensor digitorum
      longus, posttetanic potentiation is preserved for at least forty days of tenotomy
      but disappears after only 2 weeks of denervation suggests important role of
      neurotrophic influences in regulation of posttetanic responses of fast muscles.

PMID- 21961303
TI  - [Ionic and molecular mechanisms of beta-amyloid-induced depolarization of the
      mouse skeletal muscle fibres].
AB  - Excess production and accumulation of beta-amyloid peptide (betaAP) are central
      for pathogenesis of Alzheimer's disease. Numerous studies showed that betaAP
      possessed wide range of toxic effects on neurons, however the mechanism of betaAP
      influence on another types of excitable cells, for example, skeletal muscle
      fibres, is unknown. In electrophysiological experiments on the mouse diaphragm,
      we found for the first time that betaAP (25-35 fragment, 10-6 M) disturbs the
      processes of the resting membrane potential generation in muscle fibres, leading
      to depolarization by two mechanisms: 1) inhibition of Na+,K(+)-ATPase, which
      leads to loss of impact of this pump to the resting membrane potential; 2)
      increase of membrane cationic permeability due to formation of "amyloid" channels
      blocked with Zn2+ ions. Our results significantly broaden current understanding
      of mechanisms of motor disturbances and skeletal muscle pathology in Alzheimer's
      disease, inclusion body myositis and other betaAP-related disorders.

PMID- 21961304
TI  - [Participation of GABA- and dopaminergic mechanisms of the bed nucleus of stria
      terminalis in reinforcing effects of psychotropic drugs mediated via the lateral
      hypothalamus].
AB  - The purpose of the investigation was to elucidate significance of GABA and
      dopamine systems of the bed nucleus of stria terminalis for the reinforcing
      effects of a number of psychotropic drugs (opiates, opioids, psychostimulants) on
      self-stimulation of the lateral hypothalamus in rats. To the Wistar male rats,
      bipolar electrodes were implanted in the lateral hypothalamus to study self
      stimulation reaction in the Skinner box. Simultaneously, the microcannules were
      implanted into the bed nucleus of stria terminalis to inject the drugs under
      study. Some drugs, xycaine, or lidocain, a blocker of sodium influx ionic
      currents, antagonists of GABAA receptors bicuculline, D1 dopamine receptors
      SCH23390 and D2 dopamine receptors sulpiride which were administered
      intrastructurally into the bed nucleus of stria terminalis, were used for
      pharmacological analysis. Xycaine > SCH23390 = bicuculline inhibited self
      stimulation of the lateral hypothalamus. The reinforcing properties of a number
      of psychoactive drugs (amphetamine, Fentanyl, sodium ethaminal and
      leuenkephaline) were changed on the background of their action. It is concluded
      that the bed nucleus of stria terminalis controls the hypothalamic self
      stimulation via GABA- and dopaminergic mechanisms. GABA realizes the negative
      (inhibitory) action. The direct positive (activating) effect on the lateral
      hypothalamus is realized through D1 dopamine receptors, and D2 dopamine receptors
      of the bed nucleus of stria terminalis limit the positive effects of narcogenic
      drugs.

PMID- 21961305
TI  - [Contribution of nitric oxide in the mechanisms of flow-dependent vasodilation in
      normo- and hypertensive rats].
AB  - The aim of this study was to evaluate the role of nitric oxide (NO) in the
      mechanisms of arterial distensibility and intravascular pressure stability in
      normotensive and spontaneously hypertensive rats. The experiments were performed
      on the anesthetized male Wistar, Wistar-Kyoto (WKY), and spontaneously
      hypertensive rats (SHR). The abdominal aorta was cannulated and perfused with
      variable blood flow rates with subsequent determination of major characteristics
      of regional vascular function. The blockade of nitric oxide (NO) synthase
      resulted in the increase in hydraulic resistance of the hindlimb vascular bed in
      all series of the experiments. It was associated with the decrease in the
      intravascular pressure stability. The obtained results provide further evidence
      for an important role of NO in the formation of conductivity and stability of the
      arterial pressure both in normo- and hypertensive rats. However, the involvement
      of NO in the phenomenon of flow-dependent vasodilation in SHR is unlikely. The
      major difference between SHR and normotensive rats involved the ability of the
      resistive arteries of SHR to enhance vascular conductivity in response to blood
      flow enhancement. Presumably, there are some unidentified additional factors that
      are involved in the flow-dependent vasodilation in SHR.

PMID- 21961306
TI  - [Heat exchange of the rat in thermoneutral zone temperature and comparison with
      heat exchange in ambient temperature over and under it].
AB  - With the help of thermonetry and general calorimetry body temperature and heat
      production in ambient temperatures 20 degrees C, 28 degrees C, 33 degrees C were
      recorded. The experiments showed, that at the temperature 20 degrees C the rectal
      temperature was changing very little. But in ambient temperature 33 degrees C the
      rectal temperature was 40.5 +/- 0.1 degrees C.

PMID- 21961307
TI  - [The pulmonary hemodynamic changes under experimental myocardial ischemia in
      rabbits following beta-adrenoreceptors blockade].
AB  - In acute experiments in anesthetized rabbits, changes of the pulmonary
      hemodynamics following myocardial ischemia in the region of the descendent left
      coronary artery were studied as well as in control animals and after the blockade
      of beta-adrenoreceptors. The myocardial ischemia decreased the left ventricular
      myocardial contractility, cardiac output and arterial pressure, decreased the
      pulmonary artery pressure and flow. Following myocardial ischemia, the pulmonary
      artery pressure decreased less than pulmonary artery blood flow as the result of
      elevating of the left atrial pressure, meanwhile pulmonary vascular resistance
      was not changed. Following myocardial ischemia in animals after the blockade of
      the beta-adrenoreceptors, the pulmonary flow decreased the same as in control
      animals. However, the pulmonary artery pressure was decreased twofold more
      significantly than in control animals, and its diminishing was in the same degree
      as the pulmonary artery flow. Following myocardial ischemia after the blockade of
      the beta-adrenoreceptors, the pulmonary vascular resistance decreased whereas the
      left atrial pressure did not change significantly because the myocardial
      contractility decreased less than in control animals.

PMID- 21961308
TI  - [Association between level of intelligence and heart rate variability].
AB  - Earlier we discovered that heart rate variability was associated with the level
      of intelligence. The purpose of this study is to confirm this association using
      more reliable method and to define more precisely the frequency band within which
      the amplitude of the heart rate modulations is related to intelligence. 13 males
      (aged 14 to 17) were the study subjects. The total score of the computer game
      Tetris was taken as a general measure of the intelligence level. Heart rate was
      recorded electrocardiographically both at rest and during playing Tetris.
      Frequency analysis of heart rate was carried out with digital Fourier
      transformation. Correlation analysis showed that there was positive association
      between the level of intelligence and the amplitude of heart rate modulation at
      the frequencies 0.30 and 0.15 modulations per RR interval. This association is
      closer for the heart rate at rest than for the heart rate during mental work and
      for the frequency 0.30 than for the 0.15 modulations per RR interval.

PMID- 21961309
TI  - [Molecular changes in inbred mice with individual vulnerability vs resilience to
      stress-induced depressive-like state].
AB  - The C57BL/6 mice were subjected to a chronic combined stress which resulted in
      the induction of a depressive-like state. The occurrence of a depressive-like
      state was defined by a decrease in sensitivity to the reward determined by the
      diminished preference of sweetened solutions over regular drinking water. Such
      decrease is generally considered as a sign of an unhedonic-like state: one of the
      key features of clinical depression. Applied here, the paradigm in mice allows
      unhedonia induction in a subpopulation of stressed animals (54% in the current
      study); remaining mice are regarded as resilient to stress-induced hedonic
      deficit. The resilient subgroup is taken, therefore, as a "functional control"
      for those effects of stress that are not accompanied by development of the stress
      induced depressive-like state in mice. The analysis of the mRNA extracted from
      the hippocampi of stress-subjected and home-cage control mice enabled the
      assessment of gene expression level of over 13 000 genes. This study showed that
      unhedonic mice are characterized by an up-regulation of 278 and down-regulation
      of 174 genes related mostly to the CNS development and functions, inter-cellular
      interactions and signalling, neurological disorders, apoptosis and behavioural
      regulation. Resilient animals demonstrated up-regulation of 924 and down
      regulation of only 29 genes that control formation of cell assemblies, molecular
      transport, CNS functioning, neurological disorders and various biochemical
      reactions. Thus, gene expression profiles in the hippocampus of susceptible vs
      resilient to stress-induced unhedonia inbred subgroups of animals are strictly
      distinct in both quantity and quality.

PMID- 21961310
TI  - [Peroxynitrite effect on the haemoglobin oxygen affinity in vitro in presence of
      different partial pressure of carbon dioxide].
AB  - Peroxynitrite (ONOO-) besides its toxic possesses regulatory action that includes
      the modulation of oxygen binding properties of blood. The aim of this work was to
      estimate ONOO- effect on the haemoglobin oxygen affinity (HOA) in vitro in
      presence of different partial pressure of carbon dioxide (CO2). The ONOO-
      presence in venous blood in conditions of hypercapnia induced oxyhaemoglobin
      dissociation curve shift leftward while in hypocapnic conditions the result of a
      different character was obtained. The revealed effect of ONOO- is realized,
      possibly, through various modifications ofhaemoglobin whose formation is
      dependent on the CO2 pressure. The ONOO- influences the HOA in different manner
      that can be important in regulation of blood oxygenation in lungs and maintenance
      of oxygen consumption in tissues.

PMID- 21961311
TI  - [Heterogeneity of the rat respiratory way responses to serotonin].
AB  - In stimulation of preganglionic and postganglionic nervous fibres of the trachea
      and stimulation of preganglionic nervous fibres of the bronchi, serotonin
      strengthened reduction of a smooth muscle to 114 %. Methysergide (1.0 mkg)
      reduced responses to serotonin to 74-77 % on the trachea and practically didn't
      influence the bronchi. Against ketanserinum (1.0 mkg) serotonin is dose-dependent
      and reduced trachea's amplitude of the constriction to 60-63% and bronchi's
      amplitude of the constriction to 75-79%. Hexamethonium (100.0 mkg) reduced the
      serotonin amplitude of the constriction of the trachea at stimulation of
      postganglionic nerve to 64% and the bronchi at all kinds of irritation to 82-84%.
      Atropine (1.0 mkg) reduced effect of serotonin in stimulation of postganglionic
      nerve and tracheal smooth muscles to 75-77%. On preparations of bronchi, atropine
      reduced the serotonin effects in stimulation of preganglionic nervous fibres to
      83% and strengthened to 117% in smooth muscles in stimulation of preganglionic
      nerve. Thus, there is heterogeneity of responses of smooth muscles of different
      sites of the tracheal-bronchial pathways of the rat to serotonin.

PMID- 21961312
TI  - [Reconciliation in hamadryas baboons, Papio hamadryas: testing the relationships
      quality hypothesis].
AB  - Post-conflict interactions between former opponents were investigated in a troop
      of hamadryas baboons, Papio hamadryas. This species is known for it's multilevel
      structure with evidently expressed hierarchy between males and females. Due to
      this fact hamadryas baboons represent an ideal object for testing the
      "relationship quality" hypothesis. The analyses were done on 436 PC-MC pairs of
      animals, which represented different social classes (harem male-female pairs,
      harem females, relatives, females from different harems. Male-male pairs, and
      female-subadult pairs). Reconciliation was practiced in different social classes
      of individuals: harem male-female pairs, harem female-female pairs, kin-kin
      pairs, male-male pairs, female-subadult pairs. Significant differences in the
      rate of reconciliatory tendency for different categories of interacting animals
      were found. Interactions between former opponents were highly selective. These
      may be interpreted as an indicator of the influence of the relation quality on
      the probability of reconciliation in hamadryas baboons.

PMID- 21961313
TI  - [Correlation of structurally-functional cardiac condition and levels of
      erythropoietin, tumour necrosis factor-alpha in blood in heart failure].
AB  - Structurally-functional myocardium parameters and their interconnection with
      erythropoietin and tumour necrosis factor-alpha levels in blood plasma of
      patients with heart failure were analysed. Prevalence of erythropoietin over
      tumour necrosis factor-alpha in blood had positive effect on myocardium
      contraction ability under acute heart failure. Improvement of pumped cardiac
      function was not registered under prevalence of erythropoietin over tumour
      necrosis faetor-a in blood of patients with chronic heart failure.

PMID- 21961314
TI  - [Genes and neurophysiological indicators of cognitive processes: a review].
AB  - This article provides an overview of the genetic association studies relating
      candidate genes with event-related potentials. This new and rapidly developing
      area may aid in elucidating the molecular basis of individual differences in
      cognitive abilities and broaden our knowledge ofneurocircuits underlying
      information processing. To date, among thousands of genes expressing in the human
      brain, only a few have been explored in relation to ERPs. Some of the
      associations found confirm and extend evidence for the involvement of particular
      neurotransmitter systems in specific cognitive operations. Others implicate genes
      of brain processes that have not been previously investigated in connection with
      ERPs and thus propose novel directions for further research of neurophysiologic
      mechanisms of cognition.

PMID- 21961315
TI  - [Functional asymmetry of electric processes in the rabbit brain cortex at
      formation of the hunger dominant].
AB  - The motivational condition of hunger and formation of the hunger dominant after
      daily food deprivation was studied in the conditions of chronic experiments on
      rabbits. It was shown, that the hunger condition was accompanied by left sided
      interhemispher asymmetry on indicators of spectral capacity of EEG frontal and
      right-hand asymmetry sensorimotor areas of the cortex. A hunger dominant was
      accompanied by falling of spectral capacity of EEG of areas of both hemispheres.
      The condition of hunger and a hunger dominant were characterized by right-hand
      asymmetry on average level of EEG coherence of frontal and sensorimotor areas. At
      transition of a condition of hunger in a hunger dominant there was an average
      level of EEG coherence decrease in areas of the right hemisphere. Electric
      processes of the cortex of the brain at a motivational condition of hunger and a
      hunger dominant were different.

PMID- 21961316
TI  - [Muscle post-effects and upright standing in healthy subjects and patients with
      sensory-motor integration disorders].
AB  - We compared the upright standing in 7 patients with sensory-motor disorders and 7
      healthy subjects (control) before and after 30-s involuntary neck muscle
      contraction. A trajectory of the center of pressure was recorded during 30-s
      standing with the eyes open, eyes closed and standing on a foam-rubber with the
      eyes open. As compared to healthy subjects, patients exhibited an increased body
      sway area during standing with the eyes open on both the firm surface and foam
      rubber and a backward shift of the center of pressure during standing with the
      eyes both open and closed. Closing the eyes affected the upright standing of
      patients to a lesser extent than standing of healthy subjects. Involuntary neck
      muscle contraction within 30 s elicited a backward shift of the center of
      pressure in healthy subjects, especially during standing with the eyes closed,
      and a decrease in the length of the center-of-pressure trajectory, especially of
      its frontal component during standing on the foam-rubber. In patients, a post
      effect of the neck muscle contraction manifested itself as a decrease in the body
      sway area during standing on the foam-rubber and relative increase in the frontal
      component of the center-of-pressure trajectory during standing with the eyes
      closed. The results suggest that the upright standing of patients with sensory
      motor disorders is more sensitive to somatosensory than visual input, and 30-s
      neck muscle contraction approach their postural stability to the age-matched
      control.

PMID- 21961317
TI  - [Cardiovascular reactivity to emotional texts in subjects with low and high level
      of psychoticism].
AB  - The article presents the results of comparative study of groups of subjects with
      low and high level of psychoticism. Heart rate, heart rate responses to
      inspiratory and expiratory Valsalva maneuvers, and blood pressure were measured
      before and after presentation of the texts with validated negative content in
      groups of subjects with low and high psychoticism scores. It was hypothesized
      that subjects with high level of psychoticism would be less engaged in the
      processing of negative contents of the texts and their physiological reactivity
      (physiological resources submitted for support of cognitive processing) would be
      less pronounced compared to subjects with low level of psychoticism. Significant
      main effect of psychoticism was obtained for changes in heart rate to expiratory
      Valsalva maneuver after presentations of the texts. Significant interaction
      effects of gender and psychoticism were obtained for systolic blood pressure.
      Other cardiovascular variables were not sensitive to the level of psychoticism.
      These effects of psychoticism were independent of other individual traits, such
      as neuroticism, extraversion, lie (social desirability), anger, trait anxiety and
      depression.

PMID- 21961318
TI  - [Event-related potentials to visually presented verbal stimuli in the examination
      stress condition].
AB  - The work is aimed at the study of ERPs to visually presented verbal stimuli in
      the examination stress condition. EEG was recorded while participants made a
      decision whether or not visually presented words were related to a given
      category. Three types of stimuli were presented: familiar words related and
      unrelated to the given category, and unfamiliar words. Components N170, P170 and
      N400 of the ERP to familiar words unrelated to the given category and unfamiliar
      words were higher in the stress condition than in a usual experimental situation.
      Component P600 was higher in the stress condition for all types of stimuli. It
      was suggested that enhanced N170/P170 and N400 components reflect changes in the
      cognitive functions ofword processing, whereas the increase in P600 is related to
      nonspecific arousal in the stress condition.

PMID- 21961319
TI  - [Peak alpha frequency and psychopathological symptoms in schizophrenia].
AB  - Spectral characteristic of the alpha activity (frequency of the maximum spectral
      peak) were comparatively studied in schizophrenic patients with predominance of
      positive or negative symptoms and healthy subjects in the resting state and
      during cognitive task performance. In patients with negative symptoms, the
      spectral peak frequency of the alpha activity (8-13 Hz) was decreased at rest as
      compared to healthy subjects in all cortical areas. In patients with positive
      symptoms, the peak frequency of the alpha rhythm in the occipital cortical areas
      was higher than in healthy subjects. The performance-induced increase in the
      alpha-rhythm peak frequency during cognitive tasks was less expressed in
      schizophrenics than in healthy subjects. A correlation of these characteristics
      with psychopathological symptoms was revealed. The results suggest a difference
      in neurophysiological mechanisms underlying positive and negative symptoms in
      schizophrenia.

PMID- 21961320
TI  - [Dynamics of driven rhythm in neuronal assemblies in sensorimotor and visual
      cerebral cortices in rabbit].
AB  - Coincident activity of pairs of neurons in the sensorimotor and visual areas of
      the cerebral cortex was studied in naive, learning, and trained rabbits during
      the formation of a hidden excitation focus in their central nervous system (a
      defensive dominanta) of the rhythmic nature. In the trained rabbits (as compared
      to the naive animals), percent of neuronal pairs (both neighboring and distant)
      in whose coincident activity the rhythm of stimulation prevailed was higher. In
      the visual cortex, percent of such pairs was significantly higher only for the
      distant neurons. Analysis of interaction between neurons in the visual and
      sensorimotor cortices revealed increasing the number of neuronal pairs with the
      driven rhythm while training. Such an increase was observed when both
      sensorimotor and visual neurons were considered as leading.

PMID- 21961321
TI  - [The role of serine/threonine and tyrosine protein kinases in the depression of
      cholinosensitivity in Helix lucorum neurons in the cellular correlate of
      habituation].
AB  - Inhibitor ofadenylate cyclase (SQ 22,536) and inhibitors ofserin/threonine
      protein kinases A (PKA -Rp-cAMPS), G (PKG - H-Arg-Lys-Arg-Ala-Arg-Lys-Glu-OH),
      calcium/calmodulin-dependent kinase II (CaMKII - KN-93), p38mitogen-activated
      (MAPK - PD 169316), and tyrosine protein kinases (genistein), including their Src
      family (PP2), weaken the depression of the acetylcholine-induced inward current
      (ACh-current) in command Helix neurons of defensive behavior under conditions of
      rhythmical local acetylcholine applications to the soma in the cellular analogue
      of habituation. Selective inhibitor of protein kinase C (PKC - chelerythrine)
      does not change the depression of the ACh-current. Mathematical simulation of the
      influence of the inhibitors applied on a number of membrane-connected
      acetylcholine receptors made it possible to obtain the design curves consistent
      with the experimental curves of the ACh-current depression. The experimental data
      and the results of calculations allowed us to make the following assumptions. The
      reversible depression of sensitivity to ACh of command Helix neurons of defensive
      behavior in the cellular correlate of habituation depends on the decrease in the
      number of membrane-connected ACh receptors as a result of activation of several
      serine/threonine protein kinases: A, G, CaMKII, p38 MAPK (without the
      participation of PKC), and tyrosine protein kinases including the family of Src
      kinases. The main targets of all protein kinases under study (excluding PKC) in
      command neurons are the proteins of cytoskeleton (actin microfilaments and
      microtubules). Phosphorylation of these proteins evokes polymerization and
      stabilization ofactin microfilaments, stabilization of the main microtubule
      protein tubulin, a change in the activity of motor proteins responsible for the
      speed of receptor endocytosis and exocytosis. The PKG action is indirect via the
      modification of actin-myosin interaction. Protein kinase A, CaMKII, and tyrosine
      Src-kinase phosphorylate also proteins activating receptor translocation into
      clathrin-coated membrane invaginations during endocytosis.

PMID- 21961323
TI  - [The method of correlation analysis of EEG synchronism and its possibilities].
AB  - A new method for estimation of EEG synchronism based on the analysis of
      correlation between amplitude modulation processes (envelopes) is considered. The
      efficiency of the given method is shown in different aspects: for detection of a
      topographical pattern, for analysis in frequency domains, for estimation of
      stability of the functional state and its changes, for detection of heterogeneous
      subgroups of subjects and outliers, for analysis of individual and group
      distinctions and distinctions in synchronism between symmetrical pairs of leads
      and hemispheric asymmetry, and for classifying division between mentally healthy
      subjects and deviations of schizophrenic spectrum with reliability approaching
      100%.

PMID- 21961322
TI  - [The psychomotor test for research of eye-hand coordination at performance of
      monotonous activity on tracking target].
AB  - Visual-motor coordination is necessary for successful performance of everyday
      activities. Many tasks, such as driving or operating devices in the workplace,
      require a variety of coordination patterns with different levels of compatibility
      between the eyes and the hand. The psychomotor test was developed which makes it
      possible to analyze visual-motor coordination disorders caused by a decrease in
      the level of wakefulness. A small circular target (14 mm in diameter) was moving
      with a low constant velosity (12 mm/s) in a circular trajectory (80 mm in
      diameter) with a period of 20 s. Subjects were instructed to keep the mouse
      driven cursor inside a target, overstepping the limits of the moving target was
      considered as an error. To test the attention level, an additional stimulus was
      introduced which appeared for 3 seconds with an interval of 15 to 40 s. When the
      stimulus appeared, it was required to touch it with the cursor and click the
      mouse button. Cursor trajectories have a temporal resolution of 120 Hz. Eye
      movements were recorded with a PC-based Eyegaze Development System (LC
      Technologies, USA) measuring corneal reflectance with a collection rate of 120
      Hz. Monotonous character of the test performance induced drowsiness and led to
      errors 25-30 minutes after the beginning of the experiment. Changes in
      physiological vigilance level was evaluated with EEG recording. Analysis of the
      dynamic characteristics of smooth and saccadic eye movements and hand movements
      showed their high sensitivity to a decrease in efficiency of operator's activity
      caused by a drop in the level of wakefulness. It is suggested that further
      development of this approach to measuring eye-hand coordination will promote
      working out a contactless method for the express diagnostics of the critical
      levels of drowsiness as well as for the definition of professional
      characteristics of an operator.

PMID- 21961324
TI  - [On the informative value of coherence analysis in clinical EEG studies].
AB  - Within the framework of discussion about the informative value of the method of
      coherent analysis, results of successful clinical application of this method of
      EEG processing in different morbid conditions are reviewed. Not denying the
      theses proposed by the opponent about the imperfection of methodological
      maintenance of the EEG coherent analysis and incompatibility of the results
      received with different software, the ways of overcoming these difficulties are
      specified. First of all, it is offered to unify procedural conditions of the
      technique. The thesis of the opponent that calculation errors are influenced by
      hypothetical "noise" (all signals of the environment) is regarded skeptically, as
      it could not be found in patients with "zero" coherence with the diagnosis of
      brain death. Some doubts are cast upon the prospect of replacement of the
      coherent analysis with an artificial envelope of the modulated groups of waves in
      assessment of synchronous processes of the brain. It is concluded that all
      technological and methodological problems of application of the EEG coherent
      analysis existing now can be overcome.

PMID- 21961325
TI  - [Chronic obstructive pulmonary disease: strategic aspects of treatment].
AB  - The article characterizes current strategy of treatment of chronic obstructive
      pulmonary disease (COPD), contains epidemiological data, draws attention to
      various phenotypes of COPD which determine individual approach to therapy.
      Individual treatment programs must consider stage of the disease, its
      progression, comorbid pathology. Pharmacological and non-pharmacological
      treatment methods are outlined. It is important to give therapists advanced
      training in COPD diagnosis and treatment.

PMID- 21961326
TI  - [Immunomodulating effects of macrolides: areas of possible clinical use in
      pulmonology].
AB  - The review is devoted to non-antibacterial effects of macrolides in patients with
      respiratory diseases: bronchial asthma, bronchoectasis, chronic obstructive
      pulmonary disease, chronic rhinosinusitis, mucoviscidosis, diffuse
      bronchiolithiasis, severe flu, posttransplantation obliterating bronchiositis.
      The discussion covers mechanisms of an immunomodulating action of macrolides.
      Current data base on non-antibacterial effects of macrolides is analysed.

PMID- 21961327
TI  - [Current aspects of pathogenetic therapy in tuberculosis].
AB  - The review presents principles of pathogenetic therapy in tuberculosis and
      current trends in pharmacotherapy: immunocorrection, prophylaxis, chemotherapy
      side effects management. Immunocorrection is illustrated by treatment with drugs
      of a polyvalent action - glutoxim and cyclopheron. Mechanisms of their immune
      action are outlined. As to hepatoprotection, remaxol is an effective
      hepatoprotecting medicine improving energy supply to hepatocytes and their
      membranes resistance to lipid peroxidation, reactivating enzymes of antioxidant
      defense. Remaxol has an antioxidant/antihypoxic action, is the most promosing
      metabolic corrector with hepatoprotective activity.

PMID- 21961328
TI  - [Amiodaron: decades of administration].
AB  - The review of long-term international clinical experience with amiodaron covers
      pharmacological properties of the drug, mechanisms of development of its
      pharmacodynamic effects basing on its action on ionic channels, receptors, impact
      on thyroid function. Unique pharmacokinetics of amiodaron, high antiarrhythmic
      efficacy of the drug in supraventricular and ventricular arrhythmia, positive
      experience in primary and secondary prevention of sudden death are characterized.
      Amiodaron is effective in patients with atrial fibrillation including those with
      organic heart disease and chronic cardiac failure. It is safe in relation to
      different cardiac side effects which are minimal but has some non-cardiac side
      effects which require control during long-term treatment.

PMID- 21961329
TI  - [Prolongation of enoxaparin therapy to one month promotes recanalization of the
      occlusively thrombosed deep veins].
AB  - AIM: To compare effects of prolongation of the treatment with therapeutic doses
      of enoxaparin to 1 month on recanalization of occlusively thrombosed deep veins
      (OTDV) of the limbs with results of standard therapy with unfractionated heparin
      (UFH). Both treatments were followed by warfarin administration. MATERIAL AND
      METHODS: Thirty patients were selected from 111 patients with a history of deep
      vein thrombosis (DVT) and/or pulmonary artery embolism according to the following
      criteria: the presence of occlusive thrombosis of one deep vein minimum; the
      absence of DVT for 12 months of follow-up. Patients of group 1 (n = 15) received
      standard therapy (UFH for at least 5 days) with switch to warfarin. Patients of
      group 2 (n = 15) received therapeutic doses of enoxaparin (1 mg/kg each 12 hours)
      for 30 days minimum with switch to warfarin. Follow-up was 12 months. Ultrasonic
      duplex angioscanning of the limbs was made at baseline, 1, 3, 6 and 12 months
      after treatment start. RESULTS: After follow-up month 1, 3 and 6 number of
      patients with occlusive DVT was significantly less in group 2. All the patients
      given enoxaparin achieved recanalization of OTDV within 3 months of treatment.
      OTDV recanalization was not achieved in 20% patients of group 1 even 12 months
      after treatment start. CONCLUSION: Prolongation of enoxaparin treatment to 1
      month followed by warfarin treatment is superior to standard UFH treatment
      followed by warfarin in providing recanalization of OTDV within 3 months of
      treatment. Moreover, this treatment predicts persistence of recanalization within
      12 months of anticoagulant therapy.

PMID- 21961330
TI  - [Role of uric acid in development of essential hypertension: modern conceptions].
AB  - The article deals with current studies on the role of uric acid (UA) in
      development of cardiovascular diseases. The results of large prospective trials
      are presented which have revealed a pathogenetic role of UA in development of
      essential hypertension. Clinical trials demonstrated elevated concentrations of
      UA in hypertensive patients. Experimental evidence suggests UA involvement in the
      processes of nonspecific inflammation, oxidant stress, endothelial dysfunction.
      It is shown that elevated UA levels in blood serum lead to affection of target
      organs.

PMID- 21961331
TI  - [Helicobacter pylori: what schemes of eradication are essential today?].
AB  - Current approaches to treatment of Helicobacter pylori infection, basic
      international recommendations, problems of growing H. pylori resistance to
      antibiotics are reviewed. Much attention is given to prospects of new eradication
      schemes, for example combinations based on bismuth tripotassium dicitrate and
      successive treatment schedules.

PMID- 21961332
TI  - [Diagnosis and treatment of gastroesophageal reflux disease].
AB  - The lecture presents modern interpretation of the term "gastroesophageal reflux
      disease" (GERD) and Montreal classification of this disease with emphasis on non
      erosive reflux disease and risk to develop Barret's esophagus which is a widely
      prevalent precancer condition frequently transforming into esophageal
      adenocarcinoma. Description is given of GERD causes, mechanisms of development,
      diagnostic and differential diagnostic signs of the disease, a high risk of
      bronchial asthma in GERD patients, basic treatment principles including healthy
      way of life, pharmacotherapy (antacids, alginates, prokinetics, proton pump
      inhibitors, etc.).

PMID- 21961333
TI  - [Current methods of systemic amyloidosis diagnosis and monitoring of its course].
AB  - AIM: To determine clinical significance of measuring blood levels of protein
      precursors of AA- and AL-amyloidosis - SAA and immunoglobulin free light chains
      (ILC), respectively. MATERIAL AND METHODS: SAA concentrations were studied with
      ELISA in 43 rheumatoid arthritis (RA) patients including complicated with
      reactive AA-amyloidosis (n = 31). Inflammation activity and its severity were
      studied (indices Li, richi, HAQ, DAS4). A modern quantitative nephelometric
      method Freelite estimated ILC levels in 31 patients with AL-amyloidosis. RESULTS:
      Patients with RA complicated with AA-amyloidosis and free of it had a strong
      correlation between blood serum SAA concentration and activity of joint disease.
      Elevated SAA concentrations to 160 mg/l (normal 10 mg/l) were detected in many
      patients with clinical remission of the joint syndrome. Significal inhibition of
      AA-amyloidosis progression was seen only in SAA concentration drop under 60 mg/l.
      For AL-amyloidosis patients ILC fall by less than 3 normal value means a 6-time
      increase in chances of a favourable outcome. CONCLUSION: Monitoring of blood
      levels of proteins precursors of AA- and AL-amyloidosis is a key factor in
      prognosis of the disease and treatment efficacy.

PMID- 21961334
TI  - [The role of lipid metabolism disorders in kidney disease in metabolic syndrome
      associated with obesity].
AB  - AIM: To study the role of lipid metabolism impairment in renal disease in
      patients with metabolic syndrome associated with obesity. MATERIAL AND METHODS:
      Lipid metabolism was studied in 77 patients with metabolic syndrome (MS) aged
      from 17 to 63 years (mean age 48 +/- 9 years). Lipid abnormalities were analysed
      in groups of patients with different degree of obesity: group 1 - body mass index
      (BMI) 25-29.9 kg/m2 (n = 13), group 2 - BMI 30-39.9 kg/m2 (n = 49), group 3 - BMI
      > 40 kg/m2 (n = 15), and in groups of patients with different insulin resistance
      (IR) : group 1 - HOMA-IR < 2; n = 12; group 2 - HOMA-IR 2 - 4; n = 27; group 3
      HOMA-IR > 4; n = 32). Correlation between plasma lipid composition abnormalities
      and markers of renal disease were studied with correlation analysis. RESULTS:
      Lipid disbolism in MS patients was characterized with elevated level of
      triglycerides, total cholesterol (TC), VLDLP cholesterol, low level of HDLP
      cholesterol. A significant relationship was detected between defective blood
      lipid composition and renal dysfunction: rise of microalbuminuria, proteinuria,
      creatinin, inhibition ofglomerular filtration rate. CONCLUSION: The changes found
      characterize lipid metabolism disorder as an independent factor of kidney disease
      in patients with MS.

PMID- 21961335
TI  - [Correction of atherogenic dyslipidemia with honey, pollen and bee bread in
      patients with different body mass].
AB  - AIM: To assess efficacy of treatment of patients with atherogenic dyslipidemia
      (ADL) with beekeeping products (honey, pollen, bee bread). MATERIAL AND METHODS:
      ADL parameters were examined in 157 patients (64 males and 93 females) aged 39 to
      72 (mean age 61,7 + 8,5 years) with ADL. Products of beekeeping were given in the
      absence of allergy and individual resistance to honey, pollen, bee bread. The
      patients were divided into four groups: patients on hypolipidemic diet only, on
      diet and honey or pollen, on bee bread, combined treatment - diet, honey, pollen.
      RESULTS: A significant hypolipidemic effect was registered in patients taking
      honey in combination with pollen (total cholesterol decreased by 18,3 %, LDLP
      cholesterol by 23,9 %) and bee bread (total cholesterol decreased by 15,7 %, LDLP
      cholesterol by 20,5 %). CONCLUSION: Improvement of blood lipid composition in
      taking honey and pollen in overweight (body mass index - BMI 25 - 30) and obese
      (BMI over 30) patients occurs only in loss of body mass.

PMID- 21961336
TI  - [Progress in gene therapy].
AB  - Recent progress in gene therapy, current status of investigations in this area of
      experimental medicine are reviewed. Much attention is given to gene-therapeutic
      approaches the efficacy of which is proved in clinical trials.

PMID- 21961337
TI  - [Therapy of acute massive blood loss in a hemophilic patient: case report].
AB  - A case is reported of management of massive intraoperative blood loss in a male
      patient with severe hemophilia. Extirpation of hip pseudotumor with one-stage
      osteosynthesis with an intramedullary joint-pin in a 43 year old male patient was
      accompanied with 7.5 l blood loss. The infusion-transfusion therapy (ITT)
      contained transfusion media about 1/3 of the total volume, fresh-frozen plasma
      and erythrocyte-containing media were used 1:1. Infusion solutions consisted of
      balanced polyelectrolytic solutions, hydroxyethylated starches 130/0.4,
      hyperchaes. Intraoperative normovolemic hemodilution and reinfusion of wound
      blood were made (CellSaver). ITT target markers were standard hemodynamics
      control tests. Hemostasis monitoring was conducted with thromboelastography.
      Complex ITT based on modern principles of clinical transfusiology provided a
      complete and safe compensation of massive intraoperative blood loss in a patient
      with severe hemophilia.

PMID- 21961338
TI  - [Reforms of practical medicine in the period of the first scientific revolution (
      XVII century - 70-ies of XVIII century). Communication 2. Development and
      introduction of new therapeutic-diagnostic concept].
AB  - Reforms in practical medicine in the course of the first scientific revolution
      are described. This period indicates a rise of a principally novel therapeutic
      diagnostic conception. Main lines of this conception are presented and
      consequences of its introduction are analysed.

PMID- 21961339
TI  - [Causes of non-use of postpartum contraceptive method among adolescent mothers].
AB  - OBJECTIVE: To determine the causes of non postpartum contraceptive use among
      adolescent mothers. PATIENTS AND METHODS: We conducted a cross-section
      descriptive study. We included women who asked for attention of an obstetric
      event in 2002, we identified those were in immediate postpartum period, and we
      selected those that did not began a birth-control method. Data were collected
      directly with an interview and revision of the file, later on they were coded and
      processed manually; the causes of non contraceptive use were classified in:
      attributable causes to patient: personal, religious, moral, familiar, cultural,
      etc. Reasons, when they received information and advice or when they did not
      assist to educational actions; attributable causes to hospital: technique
      administrative factors, insufficient educational communication activities by
      service provider; and attributable causes to medical indication: presence of risk
      factors for health women. The statistical analysis was carried out using
      frequencies and percentages. RESULTS: We found 261 women, we identified 160 (61%)
      in immediate postpartum period, 52 (32%) they did not began contraceptive use.
      CONCLUSION: The causes of non postpartum contraceptive use among adolescent
      mothers were attributable to themselves in 75%, in 21% to the medical unit, and
      4% to medical indication.

PMID- 21961340
TI  - [Intacytoplasmic sperm injection: reproductive reality in couples with
      sterility].
AB  - BACKGROUND: The intacytoplasmic sperm injection (ICSI) is the assisted
      reproduction technique (ART) that currently offers satisfactory results to
      infertile couples. The use of epididymal surgical retrieval (percutanean
      epydidimal sperm aspiration: PESA) and testicular sperm retrieval (testicular
      sperm extraction: TESE) combined with ICSI has come to bring a high response to
      azoospermic male. OBJECTIVE: To communicate the results obtained from the
      Institute for the Study of Human Conception, in Monterrey, NL, with the
      application of the ICSI technique with ejaculate sperm and in azoospermic
      patients using sperm obtained from PESAor by testicular sperm extraction TESE.
      METHODS: From January 1999 to December 2003 1,436 couples were studied at the
      Institute for the Study of Human Conception, Monterrey, Mexico; 729 cases
      underwent to ICSI (50.8%), 670 used the ejaculate sperm, in 37 cases (5%) PESA
      and 22 cases (3%) TESE. These patients were treated as usual: controlled ovarian
      hyperstimulation (COH) with FSHr alone or combined with HMG or LHr, use of GnRH
      analogs (agonist o antagonist), follicular monitoring up to the presence of 3
      follicles longer than 18 mm; ovular retrieval 34 h after HGC application and
      embryo transfer in days 3 or 5 of development. RESULTS: No statistically
      significant difference was noted in the woman's age (p = 0.623), type and time of
      sterility (p = 0.446, 0.150), neither in FSH, LH and estradiol levels (p = 0.549,
      0.623, 0.685). The middle age of the male had significant difference between PESA
      (38.9 +/- 7.3) and ejaculated sperm (36.1 +/- 6.4) (p = 0-024). The pregnancy
      rates among groups of the ejaculate sperm, PESA and TESE were 32.8%, 43.2% and
      40.9% respectively, without significant difference (p = 0.327), neither in
      implantation rates: 11.2%, 26% and 11%, respectively (p = 0.153). CONCLUSIONS:
      The technique of ICSI and use of PESA and TESE offer satisfactory results in
      infertile couples, including azoospermic male.

PMID- 21961341
TI  - [Analysis of results of intrauterine insemination performed once or twice per
      stimulated cycle].
AB  - OBJECTIVE: To compare double homologous versus only one intrauterine insemination
      (IUI) by stimulated cycle. PATIENTS AND METHOD: In a prospective, comparative
      study 138 patients were included, who underwent to intrauterine insemination; not
      inclusion parameters were: patients with cancelled cycles by poor response or by
      ovarian hyperestimulation syndrome risk. Patients were divided in two groups:
      Group 1 (N = 69) one insemination at 36 hours after human gonadotrophin chorionic
      hormone (hCG) and group 2 (N = 69) two inseminations 24 and 48 hours after hCG.
      Sperm separation was done with swim up, wash and resuspended or isolate
      techiques, and ovarian stimulation was done with recombinant FSH, menotrophins or
      clomiphene citrate. Statistical analysis was made by T Student and chi2 tests.
      RESULTS: The overall pregnancy rate was 13.04% per cycle; and seminal
      characteristics after seminal preparation were similar. We observed better
      pregnancy rates in the patients with ovulatory dysfunction and endometriosis
      (14.9% and 18.2%). No differences were established in pregnancy rates when
      patients were compared in function to seminal preparation. CONCLUSIONS: Double
      IUI at 24 and 48 hours after hCG has the same results in pregnancy rates than
      only one IUI correctly indicated 36 hours after hCG, but the costs increases in
      double insemination.

PMID- 21961342
TI  - [Influence of the use of oral contraceptives as risk factors for human
      papillomavirus infection and cervical intraepithelial neoplasia].
AB  - OBJECTIVE: To study the influence of oral contraception use as risk factor for
      human papillomavirus infection (HPV) and progression to cervical intraepithelial
      neoplasia (CIN). MATERIALS AND METHODS: A prospective, transversal and
      comparative study of 84 female patients in reproductive age that had used oral
      contraception for more than three years as birth control method and who had CIN
      mild (CIN I), moderate (CIN II) or severe (CIN III) associated or not to HPV
      infection documented by colposcopy, pathology and cytology was done. 84 cases and
      60 controls submitted to a directed interrogation were studied. Differences among
      groups were determined by linear regression, multivariance and logistic
      regression tests, p <0.05 was considered statistically significant. RESULTS:
      Average age for cases and controls was 37.5 and 36.2 years, respectively. The 70%
      of patients started their active sexual life in the second decade of their life.
      The most frequent age was 18 and 19 years. 50.6% of these patients had more than
      one sexual partner, two in average. 67.8% of cases had HPV infection and applying
      the multivariance analysis: sexual partners (p < 0.05), age at first pregnancy (p
      < 0.05) and oral contraception use (p < 0.05) were considered statistically
      significant. According to the CIN grade, the HPV presence was found as highly
      statistically significant (p < 0.001). Oral contraception use was found as risk
      factor for HPV infection by logistic regression (p = 0.0242); OR = 3.2714; CI =
      1.1670-9.1702. As for the CIN degree, HPV presence was found as highly
      significant (p = 0.0001); OR = 2.4158; CI = 1.7150-3.4028. CONCLUSION: A high
      incidence of HPV was found in our study. This is an important risk factor during
      cellular transformation, so the use of oral contraception as birth control method
      could accelerate the viral oncogenes expression present in HPV cellular genome.
      It is highly recommended to discard HPV infection before prescribing oral
      contraception as birth control method.

PMID- 21961343
TI  - [Ovarian denervation and polycystic ovary].
AB  - BACKGROUND: Ovarian inervation is limited to the superior pedicle and ovarian
      artery to loose itself within the gonadal smooth muscle. Hence, it is far from
      clear how is it that the ovary preserves its communication with hypothalamic and
      pituitary structures for feedback regulation. There is a lack of precision
      concerning structures and mechanisms involved in the genesis of polycystic
      disease. OBJECTIVE: To know the role of inervation associated to hormone stimuli
      in developing polycystic ovaries. MATERIAL AND METHODS: Groups of Sprague Dawley
      rats were studied: group 1, whom received cornoil (vehicle) served as controls;
      group 2 had estradiol valerianate (EV) and group 3 was exposed to phenol for
      denervation and also received estradiol valerianate (EV). After sacrifice,
      ovaries were exposed and saved in a formol solution until preparation and
      staining with hematoxilin-eosin and for immunochemical reaction using specific
      monoclonal antibodies for nerve tissue (PS-100 & GFAP). RESULTS: Biologic
      response was considered when follicle dilation was seen under microscopy
      evaluation. The ovaries with higher follicle development belonged to group 2 (EV)
      while preserving intrinsic follicular nervous activity as shown by a positive
      immunoreaction to PS-100 & GFAP. Those denervated and exposed to EV (group 3) did
      not show significant changes in follicular size resembling controls. CONCLUSIONS:
      The presence of neural activity is vital for development of cysts and the neural
      mechanisms involved seemed to lie within the ovarian cells.

PMID- 21961345
TI  - [About iatrogeny].

PMID- 21961344
TI  - [Leptin and its influence on the main gynecoobstetric diseases].
AB  - Leptin is a protein hormone synthesized and secreted by adipose tissue and also
      probably in other organs and systems in human body. It has multiple functions
      such as to regulate feed intake and energy balance, gonadal regulation, action in
      the hypothalamo-pituitary-gonadal axis, regulates the metabolism of the fetal
      placental unit in the pregnancy, fertility and reproductive systems, actions in
      the endometrium, mammary gland with corresponding influences on important
      physiologic processes such as menstruation, pregnancy and lactation. In the
      gynecologic surgery the serum leptin concentration is also modified. The
      knowledge of serum leptin concentration in the oncological diseases is going-up.
      Leptin is modified in the choriocarcinoma, Meigs' syndrome and other tumors. A
      better understanding of regulatory mechanisms will have direct clinical
      significance, as leptin has been proposed to impact on those causes of human
      perinatal morbidity and mortality that are associated with abnormalities of fetal
      maturity and development, general concept growth, trophoblast endocrinology, and
      placental sufficiency. Further investigations in this area will be necessary to
      improve new knowledge and a better understanding of the actions about this
      hormone.

PMID- 21961346
TI  - [Uterine fibromyoma and pregnancy. 1949].

PMID- 21961347
TI  - [Molecular detection of human papillomavirus in women with cervical condylomas
      treated with trichloroacetic acid].
AB  - OBJECTIVES: 1) To determinate the presence of human papillomavirus (HPV) in women
      with cervical condylomas after the trichloroacetic acid application by the
      polymerase chain reaction (PCR) test, and 2) to validate the colposcopy test
      versus the PCR (gold standard). PATIENTS AND METHODS: A selected sample of 28
      women of 18 to 45 years old with cervical condyloma acuminate, without evidence
      of cervical neoplasic lesion and with positive diagnosis of HPV with PCR was
      included. beta-globin gene was used as internal control and as DNA integrity
      marker. Women included in this study were divided in: treated group (n = 14),
      which were treated just one time with trichloroacetic acid to 90% in the cervix,
      the cul de sacs and the vagina areas, and placebo group (n = 14), which were
      treated with physiological saline. After eight weeks of being applied the
      treatment, each one of the 28 women was HPV diagnosed again by colposcopy and
      PCR. RESULTS: All women amplified for the beta-globin gene. In the treated group,
      11/14 (78%) patients did not show amplification. The colposcopy showed two
      negative false, five positive false, one positive true and six negative true
      tests, revealing sensitivity of 33.33% and specificity of 54.54%. CONCLUSIONS:
      From the molecular point of view, this study showed that the trichloroacetic acid
      application causes physical destruction of the infected tissue, without detecting
      DNA damage due to the cellular desquamation. On the other hand, the colposcopy
      regarding the PCR is not an appropriate test for the diagnosis and follow-up of
      the HPV infection.

PMID- 21961348
TI  - [Serum levels of antioxidants and vitamins related to the homocystein's
      metabolism during postmenopause].
AB  - OBJECTIVE: To describe nutritional status, B6, B12, and antioxidant vitamins, as
      well as homocysteine concentrations in postmenopausal women. PATIENTS AND
      METHODS: A cross-sectional study was conducted in Mexico City. One hundred twenty
      five women were selected if they were healthy and were in their first five years
      after menopause onset. Women were spontaneously divided in two groups: women who
      did not receive any hormonal treatment for at least six months before the study
      (n = 66), and those who received hormonal treatment at the moment of the study (n
      = 59). Anthropometry was measured and a fasting blood sample from a peripheral
      vein was obtained to determine homocysteine, vitamins A, C, E, B6, B12, and folic
      acid. Results were compared with Student t-test, and a logistic regression model
      was used to calculate the risk of hyperhomocystinemia after adjusting by some
      potential confounders. RESULTS: Women who did not receive hormone replacement
      therapy presented higher body mass index and waist-hip ratio than those who
      received such treatment. In contrast, this group presented higher prevalence of
      folic acid deficiency and hyperhomocystinemia, despite they consumed higher
      amounts of folic acid in the diet. This high risk of hyperhomocystinemia was
      independent of vitamin serum concentrations and the level of physical activity
      (OR = 15.1, IC95 = 1.60,141.9). CONCLUSIONS: These results suggest that hormone
      replacement therapy may protect against overweight and central fat distribution
      that occur after menopause, but increases the risk of hyperhomocystinemia.

PMID- 21961349
TI  - [Search of Chlamydia trachomatis in 159 women from private consultation].
AB  - BACKGROUND: Chlamydia trachomatis infection is very common and is associated with
      recurring cervicovaginitis, pelvic inflammatory disease, abortion and ectopic
      pregnancy. It may cause sterility. OBJECTIVE: To determine Chlamydia trachomatis
      frequency at outpatient consultation. PATIENTS AND METHODS: One hundred fifty
      nine patients were retrospectively evaluated at the gynecology consultation, to
      whom an endocervical specimen was taken with a cotton swab to corroborate the
      presence of Chlamydia trachomatis immunofluorescent antibodies. RESULTS: Forty
      nine out of 159 cases (28.9%) were positive to Chlamydia trachomatis. After
      dividing by subgroups, 26 out of 100 women with cervicovaginitis were positive
      (26%). Eleven out of 41 cases with pelvic inflammatory disease were positive
      (26.8%). In 14 patients with recent abortion, 7 were positive (50%) and 2 out of
      4 with ectopic pregnancy were positive (50%). CONCLUSIONS: Chlamydia trachomatis
      detection in patients with cervicovaginitis, pelvic inflammatory disease, ectopic
      pregnancy and abortion will allow an appropriate treatment to avoid progressive
      damage and its sequelae to the female genital tract, reproductive and economic
      levels.

PMID- 21961350
TI  - [-Na(+)-K+ ATPase activity in vesicles of plasmatic membrane of breast cancer].
AB  - BACKGROUND: -Na(+)-K+ ATPase is a useful marker which determines the origin of
      breast cancer cells. OBJECTIVE: -Na(+)-K+ ATPase activity, as well as viability
      of plasma membrane vesicles isolated from breast carcinoma tissues were
      demonstrated by histochemical detection. PATIENTS AND METHOD: Breast carcinoma
      tissue samples of patients who attended consultation in the oncology service at
      Hospital de Ginecoobstetricia Num. 4 Dr. Luis Castelazo Ayala, IMSS were
      examined. Tissue samples from adenocarcinoma were homogenized in 4 volumes of TED
      solution at 4 degrees C (Tris-HCI 0.01 M, EDTA 0.0015 M, dithiothreitol 0.001 M,
      pH 7.4) and subsequently centrifuged. The collected sample was homogenized and
      stratified in a discontinuous sucrose gradient (20 to 50%) and then centrifuged
      for 60 min at 30,000 xg. In order to determine -Na(+)-K+ ATPase activity in
      plasma membrane vesicles, suspension was incubated at Tris-maleate 0.04 M,
      adenosine triphosphate (ATP) 0.004 M, Mgcl 20.004 M, NaCI 0.1 M y Pb (NO3) 20.005
      M, pH 7.0. Reactions were carried out for 15 min at 37 degrees C in prefixed
      vesicles in 3% glutaraldehyde in 0.1 M, cacodylate buffer stock, pH7.4 for 60
      min. RESULTS: Histochemical detection demonstrated membrane vesicles from breast
      carcinoma tissues and proved their viability after tumoral progression.

PMID- 21961351
TI  - [Prevalence of low weight at birth and related factors].
AB  - OBJECTIVE: To measure the prevalence of low birth weight and its possible
      association with risk characteristics at an international level. PATIENTS AND
      METHODS: An analytical and transversal study was performed during 2003. Newborns
      attended at the gynecological unit of the Hospital General de Zona Num. 35 in
      Cosamaloapan, Veracruz, were selected. The neonates included had a neonatal
      screening for hypothyroidism, as well as a newborn registration format.
      Pediatricians and pre-graduate interns evaluated: weight at birth, sex, maternal
      age, weeks of gestation, number of pregnancies, place of residence and the
      mother's occupation. Low birth weight was defined as the newborns that weighed
      less than 2,500 g. RESULTS: A total of 751 newborns were evaluated. In accordance
      to the characteristics of the mother, the mean age was of 25.9 +/- 5.9 years, 104
      (13.8%) were adolescents, and 256 (35.3%) were first time mothers. The low birth
      weight existed in 43 (5.7%) of the newborns, and the birth weight of 708 (94.3%)
      was > or = 2,500 g. The maternal age, the number of pregnancies, the place of
      residence and the mother's occupation were not statistically related with the low
      birth weight. CONCLUSIONS: The prevalence of low birth weight is lower than the
      data reported internationally, and it could be explained by the period in which
      the study was performed. None of the characteristics assessed as risk factors
      demonstrated to be associated.

PMID- 21961352
TI  - [Success' determinant variables in assisted reproduction].
AB  - OBJECTIVE: To perform a statistical analysis with variables that have influence
      on pregnancy rates to establish a prognostic factor of each one. PATIENTS AND
      METHODS: We performed a retrospective, descriptive, and observational study with
      240 patients that underwent to IVF-ET program. The analyzed variables were:
      infertility factor, ovarian stimulation protocol, age of patients, basal hormonal
      levels, oestradiol preovulatory levels, endometrial characteristics,
      fertilization rate, number and quality of oocytes, number and quality of embryos,
      and difficulty of the embryo transfer. RESULTS: The mean age of the patients was
      34 +/- 4.42 years old. Tubal and pelvic pathologies were the main infertility
      cause. During the statistical analysis we observed that the only variables with
      differences regarding pregnancy were the number of cells in the embryo (7.18 vs
      5.9), the fertilization rate (58.3 vs 50.1%), and the number of transferred
      embryos. With the logistic regression analysis we observed that the number of
      cells on each embryo had a relative risk of 1.37 (CI 95%; 1.15-1.63), and that
      the number of transferred embryos had one of 1.63 (CI 95%; 1.10-1.58).
      CONCLUSIONS: There are many variables that influence the pregnancy rates, but
      with our results we consider that the embryo quality, its characteristics and the
      number of transferred embryos could predict better the possibilities of pregnancy
      in IVF-ET programs.

PMID- 21961353
TI  - [Malignant phyllodes tumor with differentiation to liposarcoma. A report of a
      case and bibliographic review].
AB  - Phyllodes tumor represents less than 1% of breast tumors and 2 to 3% of the
      fibroepithelial tumors. The malignancy characteristics are the excessive growth
      and the stromal atypia with numerous mitosis. The stromal component of the
      phyllodes tumor has potential to cause metaplasia to bone tissue, cartilage, and
      to smooth and striated muscle, including their respective malignant neoplasms.
      The liposarcomatous differentiation of phyllodes tumor is extremely rare. We
      present the case of an unusual breast tumor diagnosed as phyllodes tumor, with
      sarcomatous changes on its stroma, which consists of pleomorfic and myxoid
      liposarcoma. We also comment some generalities about clinical and diagnostic
      aspects, as well as anatomopathological, therapeutic, and prognostic
      characteristics related to the current literature.

PMID- 21961354
TI  - [Tlazolteotl].

PMID- 21961355
TI  - [Cesarean section and current obstetrics. 1950].

PMID- 21961356
TI  - [Normal reference values of the pulsatility index from the uterine and umbilical
      arteries during pregnancy].
AB  - OBJECTIVE: To establish the normal reference values of the pulsatility index in
      the uterine (UtA PI) and umbilical (UmA PI) arteries during pregnancy. PATIENTS
      AND METHODS: A total of 2081 normal pregnancies with normal growth fetuses were
      evaluated with pulsed Doppler ultrasound (US) between 20 and 40 weeks of
      gestation (WG). Both, UtA and UmA, were located with color Doppler US and PI
      measured in 5 consecutive and uniform cardiac cycles. In the uterine arteries,
      mean PI from the left and right arteries (Mean UtAPI) was calculated and the
      prevalence of unilateral or bilateral "notch" documented. Normal reference values
      for each gestational week were constructed, and reproducibility analyzed.
      RESULTS: There was a negative correlation between the gestational age and PI
      values from both arteries (Mean UtAPI = 1.57 + -0.02 X WG, r2= 0.07; PI UmA =
      1.56 + -0.02 X WG, r2= 0.15). The prevalence of unilateral and bilateral "notch"
      in the uterine arteries was (median) 5% (range 3-10%), and 17% (range 4-23%),
      respectively. Reproducibility analysis for calculation of the Mean UtAPI showed
      an intraclass and interclass correlation coefficients of 0.87 (95% confidence
      intervals [CI] 0.74 - 0.93) and 0.78 (95% CI 0.59-0.88), respectively, and for
      UmAPI, 0.97 (95% CI 0.93-0.98) and 0.94 (95% Cl 0.88-0.97), respectively.
      Agreement analysis between observers for the calculation of the Mean UtAPI showed
      a mean difference of 0.01 (SD, 0.13) (95% limits of agreement [95% LA] -0.27
      0.28) and for the UmAPI mean difference of 0.04 (SD 0.16) (95% LA, -0.29 - 0.36).
      CONCLUSION: The reference values here obtained of the mean UtA PI and UmAPI can
      be applied in the clinical surveillance of normal and complicated pregnancies.

PMID- 21961357
TI  - [Her2-Neu expression in ductal adenocarcinomas of the breast gland: correlation
      with histopathological parameters and estrogen receptors' expression in Mexican
      patients].
AB  - BACKGROUND: Breast cancer is a general health problem that annually produces
      400,000 deaths worldwide. Its early diagnosis leads to high cure rates;
      nevertheless, in Mexico City this happens rarely. Her2-Neu is an oncogene that is
      expressed on breast cancer cells, with aggressive behaviour and metastasis. In
      the United States 20 to 30% of the patients present an over-expression of this
      protein. This phenomenon has been used as a prognostic parameter and as a
      predictive and indication factor for therapy with monoclonal antibodies directed
      against this protein and for therapy with taxanes. OBJECTIVE: To know the biology
      and distribution of Her2-Neu expression in Mexican breast cancer patients in
      order to evaluate its potential as a prognostic and predictive factor in the
      treatment of the breast cancer. PATIENTS AND METHOD: In the cases of invasive
      ductal adenocarcinomas of the breast we compared by immunohistochemistry the Her2
      Neu and estrogen receptor expressions with the histopathological characteristics.
      The results were evaluated statistically. RESULTS: We found 122 cases of breast
      adenocarcinoma, from which we evaluated 108 for fulfilling the selection criteria
      of invasive ductal adenocarcinoma. Patient's mean age was 51.8 +/- 13.2 years.
      The mean tumour diameter was 3.5 +/- 2.0 cm and the mean number of lymph nodes
      with metastasis was 6.8. The Her2-Neu (score 2+ and 3+) expression was found in
      36.1% of the patients. The tumour diameter and the presence of metastatic disease
      had strong relation with the Her2-Neu expression level. We did not find
      correlation with the differentiation level, the patient's age and the presence or
      absence of oestrogen receptors. CONCLUSIONS: Since the percentage of patients
      with Her2-Neu expression is high (36.1%) and there is a close relation between
      Her2-Neu expression, the tumour size and the presence of lymph node methastasis,
      the determination of the oncoprotein expression could allow a more detailed
      prognosis and the treatment with immunotherapy and anthracyclines in order to
      influence the course of the breast cancer cases.

PMID- 21961358
TI  - [Medical attitude regarding the negative of receiving blood transfusions by
      Jehovah's Witness patients].
AB  - BACKGROUND: Hemoderivative and blood transfusions without proper medical
      indication bring uncertain benefits, increase health risks and adverse effects.
      It is necessary to also consider the patient's values and preferences and the
      denial to receive transfusions. A deficient medical evaluation and an unnecessary
      transfusion can generate untoward effects regarding patients' health and safety.
      MATERIAL AND METHODS: A retrospective, observational, and transverse study of 767
      complaints for alleged denial of medical attention presented by Jehovah's Witness
      patients was undertaken, coupled with their denial to receive blood transfusions
      and their perception of the problem. RESULTS: It was established that 95.6% of
      cases studied involved adult patients, while 4.4% involved underage patients,
      with a mean of 43 years. The majority of complaints appeared at the secondary
      level of medical attention, 64.5% came from social security institutions and 19%
      from private institutions. The motive for medical consultation was surgical in
      91.9% cases. 98.7% of the complaints were due to a perceived denial of medical
      attention, associated to religious conviction. 1.3% of complaints were filed
      after having received blood transfusions, without proper patient consent. The
      major health problems were solved in different medical units from the beginning
      in 500 cases (65.2%). Medical care was provided in 450 cases, in private clinics,
      while 50 cases were cared for in public institutions without the need for
      transfusion. CONCLUSIONS: Several studies coincide on the high number of
      unnecessary or unjustified blood transfusions. To improve the quality of
      transfusion medicine steps should be taken to install specialized hospital
      committees, update the use of guidelines based on the best scientific evidence,
      as well as to respect patient autonomy.

PMID- 21961359
TI  - [Prevalence of postmenopausal simple ovarian cyst diagnosed by ultrasound].
AB  - INTRODUCTION: The high-resolution ultrasound has taken to discover small ovary
      cysts in postmenopausal asymptomatic women who in another situation would not
      been detected; these cysts frequently disappear spontaneously and rarely develop
      cancer; however, they are treated aggressively. OBJECTIVE: To know the
      prevalence, evolution and treatment of ovary simple cysts in the postmenopausal
      women in our department, since in our country there are not studies that had
      analyzed these data. MATERIAL AND METHODS: We made a retrospective and
      descriptive study in the Service of Biology of the Human Reproduction of the
      Hospital Juarez de Mexico, in a four-year period (2000-2003) that included 1,010
      postmenopausal women. The statistical analysis was made using the SPSS software
      program with which we obtained descriptive measurements in localization,
      dispersion and by a graphic analysis. RESULTS: We found a simple cysts prevalence
      of 8.2% (n = 83); the average of age at the diagnosis time was 50.76 years with a
      standard deviation of 5.55; the cysts diameter was between 0.614 to 12,883 cm
      with a mean and standard deviation of 2.542 and 1.91 cm respectively; in 27.71%
      of the cases (n = 23), the cysts disappear spontaneously in the follow up of 3 to
      36 month (mean of 14.1). Surgery was indicated in 16.46% (n = 13), by increase in
      the size of the cyst in 9 patients (11.64%) and by changes in morphology from
      simple to complex in 4 (4.82%). Tumor like markers were made only to 37 patients
      (44.57%), which were in normal ranks; no carcinoma was found in this group.
      CONCLUSIONS: The prevalence of ovary simple cysts was similar to the reported in
      literature. Risk of cancer of these cysts is extremely low when a suitable
      evaluation is made, a reason why the conservative treatment is suggested when
      these are simple cysts lesser than 5cm with Ca-125 levels within normal ranks. We
      recommend a follow up every 3-6 months by Doppler color ultrasound and tumor like
      markers for five years.

PMID- 21961360
TI  - [Obstetric behavior based on evidences. Mild preeclampsia: expectant management,
      inpatient or outpatient?].
AB  - Preeclampsia is a multifactorial disease of unknown ethiology and definitive
      treatment is delivery. Before, the tendency was to avoid maternal complications,
      for what the pregnancy was interrupted without caring the fetal conditions. For
      some decades, the expectant handling has been preferred with the purpose of
      prolonging the pregnancy so that it matures the fetus and diminish the
      consequences on the perinatal morbility and mortality. There are divergent
      opinions on carrying out it in an ambulatory or hospital way. Here these two
      behaviors are revised with base in the medical discoveries. Initially, the
      hospital handling was based more in the clinical experience (observational
      evidence) that in controlled and aleatory studies. Three studies are shown
      carried out in the United States. In three controlled and randomized tests
      published in the United Kingdom this behavior was objected and it was intended
      the monitored ambulatory handling. In other two controlled and randomized trials
      and in two comparative trials, made also in the United Kingdom, it was suggested
      that the handling should be carried out in the units of care and fetal
      surveillance. In four observational studies it was intended the ambulatory
      handling, and the National High Blood Pressure Education Program Working Group on
      High Blood Pressure in Pregnancy and American College of Obstetricians and
      Gynecologist considered it an option in selected women. The current proposal is
      summarized for the ambulatory handling of women with early mild preeclampsia.

PMID- 21961361
TI  - [Prenatal diagnosis of pentalogy of Cantrell associated to bilateral cleft lip. A
      case report].
AB  - The pentalogy of Cantrell is a rare congenital syndrome characterized by
      deficiency of the anterior diaphragm and defects of abdominal wall, the
      pericardium, the lower sternum, as well as congenital intracardiac abnormalities.
      It has usually a poor prognosis, but most cases have had incomplete variants of
      this syndrome, so it is important to make a prenatal diagnosis to determine the
      size of the wall defect and to establish a multidisciplinary management. Less
      than 90 cases have been reported in the world literature. There are no casuistic
      or even treatment criteria in Latin America. A case of a newborn in whom was
      suspected this pentalogy associated to bilateral cleft lip by an ultrasound
      examination at 25 week of gestation is described. We also comment on diagnostic
      aspects, as well as anatomopathological, therapeutic, and prognostic
      characteristics.

PMID- 21961362
TI  - [The physician-patient relationship: a forgotten need?].

PMID- 21961363
TI  - [Tube-ovarian disorders determining sterility or infertility. 1951].

PMID- 21961364
TI  - [Intrauterine transfusion in alloimmunization Rh in Mexico 1987-2008].
AB  - BACKGROUND: Diagnosis, care and prevention of hemolytic disease in fetuses and
      newborns is the most prominent historical example of a successful medical
      procedure aimed to abate perinatal morbidity and mortality caused by a disease
      which for centuries was described only unknown origin. OBJECTIVE: To review the
      perinatal outcome with intrauterine transfusion (IUT) in severe alloimmunization
      RhD over 21 years in a referral center of Mexico. The overall survival rate of
      fetuses and the relations with gestational age, and presence or absence of
      hydrops was analyzed. The authors present data about alloimmunization and a
      historical synopsis about IUT in Mexico. MATERIAL AND METHOD: A retrospective
      study was conducted from January 1, 1987, to January 31, 2008. It was collected
      only RhD immunizations. Primary outcome variables included gestational age and
      presence or absence of hydrops, type and number of IUT in each case, and we
      studied fetal and neonatal morbidity. RESULTS: A total of 531 IUTs were performed
      in 150 fetuses. Severe hydrops was found at start of intrauterine treatment in 67
      cases (45%). The survival rate was closely related to absence or presence of
      hydrops (88 and 60%), respectively. There were 123 liveborn fetuses and the
      procedure-related fetal loss rate was low (1.9%). CONCLUSIONS: This study
      confirmed good outcome with IUT for fetal anemia and the loss rate was low and
      similar to another publications. The hydrops was the principal factor in the
      survival rate because late detection and referral of fetuses is critical for
      fetal and neonatal outcome.

PMID- 21961365
TI  - [Modification to surgical technique of cesarean hysterectomy].
AB  - BACKGROUND: Bleeding is a significant cause of maternal mortality in the world.
      Obstetric hysterectomy increases maternal morbidity and mortality. OBJECTIVES: To
      describe a modified technique of cesarean-hysterectomy to limit bleeding during
      surgery in cases of placenta accreta and placenta previa, which consist of
      hypogastric artery ligation before the removal of the uterus. Another objective
      of this study is to compare maternal outcomes of patients undergoing this
      technique with the usual technique. PATIENTS AND METHOD: Comparative,
      longitudinal, closed stydy. We analyzed the records of 86 patients undergoing
      cesarean-hysterectomy surgery, from July 1, 2008 to July 31, 2009, were
      programmed 29 patients with the modified technique and 57 with the usual. The
      main outcomes analyzed were: estimated bleeding during surgery, number of packed
      red blood cells and plasma units transfused and hospital stay in intensive care.
      RESULTS: Bleeding during surgery, blood transfusion and admission to intensive
      care demand, and hospital stay were significantly lower in patients with the
      modified technique. Also there were fewer trans and postoperative complications
      in this group. CONCLUSIONS: The results of this study show that the modified
      technique of cesarean-hysterectomy derives significant reduction of maternal
      morbidity, less massive transfusions demand to manage intensive care units.

PMID- 21961366
TI  - [Perinatal complications in patients with chronic renal insufficiency on
      hemodialysis].
AB  - BACKGROUND: Pregnant patients with chronic renal insufficiency treated with
      hemodialysis experience adverse perinatal results. OBJECTIVE: To compare
      perinatal complications of patients with chronic renal insufficiency undergoing
      hemodialysis who become pregnant vs. the complications of women with chronic
      renal insufficiency not undergoing dialysis but who then require dialysis during
      gestation. PATIENTS AND METHOD: Transversal and retrospective study that included
      three patients with chronic renal insufficiency on chronic hemodialysis who
      became pregnant (group A) and three patients with chronic renal insufficiency
      without hemodialysis at the time of conception but who required dialysis during
      gestation (group B). Perinatal results were compared. Statistical analysis was
      performed with measures of central tendency and dispersion and Student t-test.
      RESULTS: Group A had 25 sessions vs. group B with 29 hemodialysis sessions (p =
      0.88). Maternal complications were anemia 100% (six cases), Cesarean delivery
      83.3% (group A 2 cases vs. group B 2 cases), preeclampsia 50% (group A 2 cases
      vs. group B 1 case), uncontrolled hypertension 50% (group A 2 cases vs. group B 1
      case), preterm delivery 50% (group A 2 cases vs. group B 1 case), transfusion
      33.3% (group A 2 cases), polyhydramnios 33.3% (group A 1 case vs. group B 1 case)
      and abortion 16.6% (group A 1 case). Fetal complications included fetal loss
      16.6% (group A 1 case), neonatal mortality 33.3% (group A 1 cases vs. group B 1
      case), prematurity 50% (group A2 cases vs. group B 1 case), fetal distress 50%
      (group A 1 case vs. group B 2 cases), respiratory failure 33.3% (group A 2 cases)
      and fetal growth restriction 16.6% (group A 1 case). CONCLUSION: Frequency of
      perinatal complications is elevated in both groups.

PMID- 21961367
TI  - [Prenatal diagnosis by amniocentesis. Clinical and cytogenetic experience in
      1,500 cases].
AB  - BACKGROUND: Genetic amniocentesis is performed in Mexico 25 years ago but only
      few works have been published. OBJECTIVE: To analyze clinical and cytogenetic
      findings in consecutive patients submitted to genetic amniocentesis. MATERIAL AND
      METHOD: An analysis was made of the clinical features, amniocentesis results and
      pregnancy outcome in 1500 consecutive cases of genetic amniocentesis. RESULTS:
      Sixty-eight fetuses with chromosomopathy (4.5%) were detected and two, with an
      inborn error of metabolism. The most frequent abnormalities were trisomy 21 (32
      cases), trisomy 18 (10 cases), trisomy 13(6 cases), 45,X (6 cases), 47,XXY (4
      cases). Pregnancy outcome is known in 474 patients (32%). There were five fetal
      losses (1%). Of the 68 cases with chromosomopathy, the outcome is known in 45, of
      which, 29 (64%) decided to have an abortion while 16 (35%) continued the
      pregnancy, six had a spontaneous abortion or perinatal death and ten had an alive
      new born. Among fetuses with normal or balanced karyotype and normal ultrasound,
      11 out of 419 (2.6%) had congenital anomalies. Two of them had a condition known
      to be related with epigenetic regulation, (Russell Silver and Angelman syndrome).
      CONCLUSIONS: Amniocentesis is a reliable and low risk method. Cytogenetic
      findings in this series are similar to those reported in the literature. Most
      patients with fetal disease decided to have an abortion. The finding of two
      patients with a condition related with abnormal epigenetic regulation suggests
      that the magnitude of this risk remains to be defined.

PMID- 21961368
TI  - [Pelvic solitary fibrous nodule, incidental finding and laparoscopic resection.
      Case report].
AB  - The solitary fibrous nodule is a rare clinical disease that mainly affects the
      pleura, but has been occasionally described in other anatomical sites. This type
      of tumors can have malignant components and therefore it is important to
      differentiate them from other retroperitoneal masses. We describe the case of a
      patient with ectopic pregnancy in whom a solitary fibrous nodule with laparoscopy
      was found. A peritoneal pelvic tumor with smooth surface, 20,2 g, firm was
      detected. The mass was independent of colon, uterus, ovaries or salpinx and was
      very near to the iliac vessels on the right side. A small fragment was biopsied
      and sent to trans surgical histopathology study and the rest of the mass was
      removed completely without complications. The histopathologic report described
      that the tumor contained sclerosed cells with collagenous bands and sings of
      hemorrhage and calcification, compatible with a benign pelvic solitary fibrous
      tumor. The solitary fibrous nodule is a rare, benign disease, but with malignant
      potential. These tumors must be resected when they are incidentally found during
      other surgical procedures or if diagnosed preoperatively. The laparoscopic
      approach has advantages in the identification and resection these tumors.

PMID- 21961369
TI  - [Assessment of the radiological diagnostic methods in obstetrics and gynecology.
      1955].

PMID- 21961370
TI  - [Detection of human papillomavirus types 16 and 18 in semen samples from patients
      in an assisted reproduction program].
AB  - BACKGROUND: The infection with human papillomavirus (HPV) represents a serious
      health problem in the world. This is because are associated with cervical cancer
      development in when HPV of high-risk type 16 and 18 are involved. A genital
      infection by these virus types are normally asymptomatic in the male and an
      infection to sexual partner is possible. OBJECTIVE: The objective of the present
      is the detection of HPV-16 and HPV-18 in semen samples from patients included in
      an assisted reproduction protocol. MATERIAL AND METHOD: Semen samples were
      obtained from 149 patients that are included in an assisted reproduction protocol
      in our institution. Semen was examined according with WHO criteria and detection
      of HPV-16 and HPV-18 was realized with real time PCR protocol with commercial
      kits. Also, conventional histology techniques were used to assess spermatozoo
      morphology and leukocyte count. RESULTS: 149 semen samples were analyzed from
      patients with an age average 37.27 (22-56 age). The 56.18% present
      oligozoospermic and take into account all patients, 59.73% was positive for HPV
      16 (29.56%), HPV-18 (16.11%) or both (14.09%). The infection with HPV-16 was more
      frequent in both oligozoospermic and normozoospermic patients. In this latter, a
      minus abnormal spermatic cells and leukocytes were found in regard to
      oligozoospermic patients. CONCLUSIONS: There is an important percentage off human
      asymptomatic male subjects that present in your semen a positive result for high
      risk papillomavirus. This is very important for the sexual partner because this
      represent a problem for public health that most be in attention.

PMID- 21961371
TI  - [Intracytoplasmic morphologically selected sperm injection (IMSI) vs
      intracytoplasmic sperm injection (ICSI) in patients with repeated ICSI failure].
AB  - BACKGROUND: Intracytoplasmic sperm injection (ICSI) is highly effective for the
      control of male factor infertility. The sperm selected for ICSI may have
      structural abnormalities undetectable to 400x as nuclear vacuoles, decreasing
      rates of pregnancy and implantation. Recent studies show that with
      intracytoplasmic morphologically selected sperm injection (IMSI), at higher
      magnification (> 6,600x), increases pregnancy and implantation rates in patients
      with repeated failure to ICSI. OBJECTIVE: To compare the results of the injection
      of selected motile sperm organelle morphology examination (MSOME) for IMSI,
      instead of the use of ICSI in patients with repeated failure to ICSI. PATIENTS
      AND METHOD: Prospective, observational cohort study. Since February 1, 2010 was
      administered IMSI to couples with at least two failed cycles of ICSI, and
      analyzed the first 30 cycles in patients under 38 years of good ovarian reserve.
      This study group was compared with the last 30 cycles of ICSI performed before
      that date, in patients with similar clinical characteristics. The IMSI was
      performed with a magnification of 7,676 increases for evaluation and sperm
      selection. RESULTS: The groups had similar clinical characteristics. The
      pregnancy rate with IMSI was better than with ICSI (63 vs. 50%), the difference
      was not significant for the size of the sample, although the trend is clear and
      clinically significant in favor to IMSI. The implantation rate with IMSI (44.8%)
      showed statistically significant differences vs. ICSI (29.7%). No significant
      differences in abortion rates. CONCLUSIONS: IMSI significantly improves the
      implantation rate in patients with repeated failure to ICSI.

PMID- 21961372
TI  - [Extreme maternal morbidity in the Hospital General Dr. Aurelio Valdivieso,
      Oaxaca Health Services].
AB  - BACKGROUND: Obstetric Morbidity Extreme (OME) is a promising addition to the
      investigation of maternal deaths and is used for the evaluation and improvement
      of maternal health services is defined as a severe obstetric complication that
      threatens the life of the pregnant woman and requires urgent medical intervention
      to prevent death of the mother. OBJECTIVE: To identify association between
      diseases and obstetric morbidity Extreme. MATERIAL AND METHOD: Transversal review
      analytical records. We searched for codes related to conditions that could cause
      extreme obstetric morbidity and the indirect causes that might cause it. RESULTS:
      The prevalence of OME 21 per 1000 newborns, diseases with greater association
      were eclampsia, liver failure and preeclampsia yielded the highest OR and
      statistical significance, the association of OME derived from surgery despite
      having a high prevalence in the analysis showed no association, in the same way
      if other variables showed association but had no significance and confidence
      intervals are below the unit that is the case of renal failure, metabolic failure
      and blood transfusion. CONCLUSIONS: The OME is caused by group entities specific
      disease (FLASOG) in most cases such as preeclampsia, eclampsia and obstetric
      hemorrhage.

PMID- 21961373
TI  - [Impact of male aging in the functional capacity of sperm through the expression
      of phosphatidyl serine and oligonucleomas].
AB  - BACKGROUND: biomolecular processes associated with aging and programmed cell
      death during spermatogenesis are well known, but not its biological significance
      in ejaculated sperm, because it ignores the behavior of these apoptotic markers
      in relation to the age of man. OBJECTIVE: To evaluate the effect of aging on the
      functional capacity of sperm and their relationship to programmed cell death
      processes. MATERIAL AND METHODS: Prospective, cross-sectional and analytical
      performed with semen samples from 25 healthy subjects 20 to 70 years old, were
      divided into two groups [(A: under 40 years) and (B: over 40 years age)]. Semen
      parameters were evaluated WHO (1999) and transformation processes biomolecular
      membrane and the expression of oligonucleosomes in the terminal cascade of
      apoptosis. Were measured by flow cytometry with an argon laser as a source of
      reading at 480 nm, the degree of cellularity discriminate negative and positive
      for each of the indicators. RESULTS: The percentage of live cells with
      phosphatidylserine translocation in the membrane (annexin-V / PI) was
      significantly higher in men older than 40 years (p <0.05). These findings are
      enriched with a significant positive correlation (r = 0.50, P <0.008) between
      early biomarker and age of the subjects. With regard to DNA fragmentation,
      although no statistically significant differences were found, it is a clear trend
      of increase as older the subjects (r = 0.51). CONCLUSIONS: The increasing age of
      the man is associated with increased expression of apoptosis, as demonstrated by
      the increased expression of phosphatidylserine translocation at the Membrane.
      Thus, this study confirms that the subject's age is associated with a decline in
      some of the seminal parameters.

PMID- 21961374
TI  - [Expression of cell adhesion molecules in the maternal fetal period of human
      gestation].
AB  - BACKGROUND: The human labor is an inflammatory process invading leukocytes
      modulated by gestational tissues. The local increase of cell adhesion molecules
      (CAMs) promotes the permanence of these leukocytes in the coriodecidua.
      Gestational tissues express ICAM-1, while circulating leukocytes expressing its
      ligand Mac-1. OBJECTIVE: To analyze, first, if the expression of CAMs in the
      fetal membranes is associated with progress of gestational age, and second, the
      expression of CAMs on circulating leukocytes in the uterus (placenta). MATERIAL
      AND METHOD: original and closed study conducted at the Instituto Nacional de
      Perinatologia Isidro Espinosa de los Reyes (Mexico City). We included samples
      from healthy women between 15 and 44 years of age with term pregnancies (> or =37
      weeks gestation). RESULTS: Real time PCR analysis showed that the expression of
      CAMs in the fetal membranes remained constant before labor. ICAM3 and ICAM1
      tended to increase during labor, while ICAM2, VCAM1, SELE and SELP decrease with
      advancing gestational age. Placental leukocytes showed a clear increase in the
      expression of ITGAM (Mac-1) during labor. CONCLUSIONS: These results show that
      the maternal-fetal interface expresses a specific combination of CAMs during
      labor, including ICAM1, ICAM-3 and Mac-1. The expression of these molecules could
      promote the retention of leukocytes in the local tissues to modulate the local
      inflammatory microenvironment during human labor.

PMID- 21961375
TI  - [Effect of merocianina-540 in the fertilizing capacity of sperm correlated with
      the expression of 3-OH terminal fragments].
AB  - BACKGROUND: The packaging of heterochromatin during spermatogenesis has been
      correlated with the expression of residual apoptotic bodies (which stain with
      merocyanine A) that will impact on sperm function in the fertilization process;
      as well as the joint expression of the transmembrane translocation phosphatidyl
      serine and oligonucleosomes. OBJECTIVE: To evaluate the expression of bodies
      stained with merocyanine in the functional processes of sperm and their level of
      agreement with apoptotic Annexin V and TUNEL biomarkers. MATERIAL AND METHOD: We
      performed a prospective, cross, including 11,000 cells belonging to semen samples
      from infertile men, were evaluated according to WHO criteria (1999), bounded by
      the lines of Tygerberg. The biomolecular transformation processing of the
      membrane and the expression of oligonucleosomes in the terminal cascade of
      apoptosis were quantified by cytometry flow, using an argon lasser as a reading
      source of 480 nm, discriminating the degree of cellularity, both negative and
      positive for each indicators. RESULTS: Because of the study design was found low
      quantification in semen parameters, motility, morphology and sperm concentration.
      The average expression of cells [DNA-PI(+) / dUTP-FITC(+)] (quantification of
      TUNEL) and [Annexin-V(+) / PI(-)] was 36.5 +/- 17.4% and 31.2 +/- 17.4%,
      respectively. By comparing the expression of TUNEL without the effect of M540
      bodies (36.3 +/- 1.7% vs. 36 +/- 1.7%) a significant difference was not
      determined. CONCLUSIONS: This study shows that there is a remnant of the primary
      processes of spermiation, which can take an important role in apoptotic and
      functional processes of the sperm. However, its expression does not affect
      measurement of biomarkers of apoptosis seminal, whose determination changed the
      diagnosis and functional perception of reproductive parameters in the sperm.

PMID- 21961377
TI  - [Gastrointestinal stromal tumor in pregnancy and control. Case report].
AB  - Gastrointestinal stromal tumors are the commonest stromal tumors of the digestive
      tract. Even though, the incidence is aproximately 10 to 20 cases per million
      people and year. More than 90% of these tumors take place in patients over 40,
      and the median age is 63. Its diagnosis during pregnancy is extremely rare. There
      are less than 10 cases reported in literature about gastrointestinal stromal
      tumors diagnosed during pregnancy. We describe the case of a patient who was
      diagnosed of gastrointestinal stromal tumor during her first pregnancy due to
      massive lower digestive bleeding and the fetus died. She underwent a small bowel
      resection and cesarean section delivery. Afterwards, she was controlled by
      obstetricians, digestive surgeons and oncologists. The following two pregnancies
      were normal, and six years since the diagnosis she is asymptomatic. Even if they
      are extremely rare tumors during pregnancy, it is very important knowing their
      diagnosis and multidisciplinary treatment; also very important is knowing their
      prognostic factors and the different possible treatments.

PMID- 21961376
TI  - [Oxytocin and syndrome of inappropriate secretion of antidiuretic neonatal
      hormone. Case report of early severe hyponatremia and literature review].
AB  - This is a clinical case presentation of a full term newborn infant who suffered
      severe hyponatremia and early seizures, associated with maternal fluid overload
      with electrolyte free solutions and high doses of oxytocin for labor
      augmentation. Although this condition has been recognized since the 1960's with
      isolated reports, this particular case has features that needs further
      investigation, not only for the unsually severe hyponatremia, but most
      importantly we think, for the prominent signs of fluid retention, the infant had,
      that suggest excessive antidiuretic activity probably due to oxytocin. These
      findings are consistent with syndrome of inappropriate secretion of antidiuretic
      hormone. Although until now there is no proof that oxytocin by itself produces
      this syndrome. We think the association is possible in certain clinical
      circumstances, such as those found in this case. We also, briefly discussed the
      pathophysiology of perinatal hyponatremia, the neonatal treatment of this
      condition and the current guidelines for the women in labor. Hyponatremia should
      not be considered a benign condition, since in the neonate, it may affect brain
      function.

PMID- 21961378
TI  - [Routine diagnosis of female infertility. 1955].

PMID- 21961379
TI  - The electronic health record imperative: transforming patient care.

PMID- 21961380
TI  - Electronic medical records: a path forward.
AB  - Health systems are moving to implement comprehensive electronic medical record
      (EMR) systems, or significant pieces of them, in the belief that EMR can be
      integrated into clinical practice and lead to improved patient outcomes and
      enhanced safety. There are substantial roadblocks to implementing EMR, including
      significant cost, the competency needed to implement, the political environment,
      organization infrastructure and culture, and how organization leaders understand
      return on investment. Complicating factors include the drive to implement EMR to
      meet meaningful use standards to qualify for a federal incentive program and
      recently publicized studies that question the value equation of the EMR as it
      relates to patient care improvements. We offer our experiences on the successful
      implementation of the EMR across the large health systems we lead. We offer
      practical advice and tips on how to achieve successful implementation, evidence
      that successful implementations improve patient care and safety, and a glimpse of
      how EMR is a significant foundation in a future of collaborative models that
      provide continuum-based care.

PMID- 21961381
TI  - How CEOs drive the clinical transformation and information technology agenda.
AB  - The United States' healthcare model is in a serious period of change and
      redirection. This era holds the potential for transformations equal in
      significance to the introduction of prospective payment system or even the
      initiation of Medicare. This article describes the considerable and unique role
      that hospital and health system CEOs must play to position their organizations to
      not only survive but lead the transformation journey, with particular emphasis on
      the information technology investment imperative. Healthcare delivery is a
      multidimensional, multidisciplinary, and matrixed model. Change is hard.
      Information technology is evolving. Add these together and we begin to see the
      challenges ahead.

PMID- 21961382
TI  - Leading from the future: leadership makes a difference during electronic health
      record implementation.

PMID- 21961383
TI  - The CEO's role in small and rural hospitals' EMR implementation.

PMID- 21961384
TI  - Driving on Main Street: the road to widespread physician EHR use.

PMID- 21961385
TI  - Constructive approaches to common problems. Chronic conditions get another look.

PMID- 21961386
TI  - Med pass makeover. A facility streamlines its medication administration program
      and boosts resident-centered care in the process.

PMID- 21961387
TI  - Meaningful HIT aids frontline caregivers. New strategies for successful
      implementation.

PMID- 21961388
TI  - Acts of kindness. One charity yields multiple benefits.

PMID- 21961389
TI  - A future estate in good SHAPE.
AB  - Claire Bradford, project director at SHAPE (the Strategic Health Asset Planning
      and Evaluation iniatitive), outlines the many benefits available to estates and
      facilities teams via the web-enabled, evidence-based application--which "informs
      and supports the strategic planning of services and healthcare assets"--and
      explains how it is regularly updated to reflect new trends and needs against a
      fast-changing healthcare backdrop.

PMID- 21961390
TI  - Backlog guidance 'flaw' addressed.
AB  - In a previous article, in the September 2010 edition of Health Estate Journal,
      "Is multi-million pound backlog a reality", independent consultant to the
      healthcare sector, Dr Melvyn Langford, highlighted what he claimed was a
      "fundamental flaw" in the way the established NHS "5 x 5 criticality grid" used
      to assess the urgency of backlog maintenance had been interpreted for many years
      by estates personnel, resulting, he said, in one Trust with a reported 12 million
      pounds sterling backlog in fact only having a 0.5 m pound sterling "backlog
      issue". Here he describes an alternative methodology, recently successfully
      tested with several pilot NHS sites, which he says corrects this flaw, and could
      have "major implications" for estates and facilities personnel under
      unprecedented pressure to cut costs.

PMID- 21961391
TI  - Driving efficiency via a 'different' approach.
AB  - Paul Boocock, director of estates and facilities management at the South Devon
      Healthcare NHS Foundation Trust, explains how he and Jonathan Gilmore, a director
      at not-for-profit healthcare sector improvement organisation, BIRCH, and the
      Collaborative Working Centre, with wide-ranging experience in the construction
      and EFM sectors, have worked with the Trust's estates and facilities management
      team to bring a "leaner" approach to its activities, in the process improving
      efficiencies and reducing waste at the Torbay Hospital.

PMID- 21961392
TI  - Cutting the cost of hospital HVAC.
AB  - Steve Ruddell, head of global marketing, Motors & Generators, at ABB, emphasises
      the importance of a good motor management and maintenance policy in getting the
      best performance from, and reducing the energy consumption of, hospitals' HVAC
      systems, also explaining why investing in energy-efficient, low voltage drives,
      and high efficiency electric motors, to control such equipment, can pay major
      dividends for estates and facilities teams.

PMID- 21961393
TI  - Securing a safer future as cuts bite.
AB  - Government plans for NHS reforms will have a direct impact on the specification
      of security products within hospitals, surgeries, and care facilities, argues
      Tina Hughan, head of marketing for ASSA ABLOY, who considers the likely
      ramifications, and how security products must adapt to accommodate these changes.

PMID- 21961394
TI  - Smarter running can keep buildings fit.
AB  - Simon England, director at Accenture Health UK, outlines the benefits of an
      "assessment-based" approach to creating "smarter" healthcare buildings with
      reduced running costs and a lower carbon footprint.

PMID- 21961395
TI  - Striking design suits St Andrews skyline.
AB  - Creating a new hospital that proves itself to be sustainable on a greenfield site
      is quite a challenge. Paul Bell, director at Ryder Architecture, describes how
      the St Andrews Community Hospital and Health Centre has been delivered to achieve
      just that for NHS Fife.

PMID- 21961396
TI  - The Advanced Tactical Parachute System (T-11): injuries during basic military
      parachute training.
AB  - BACKGROUND: Since the 1950s, the standard U.S. military troop parachute system
      has been the T-10. TheT-10 is currently being replaced by the newer T-11 system.
      PURPOSE: This investigation compared injury incidence between the T-10 and T-11
      military parachute systems. METHODS: Participants were students in basic
      parachute training at the U.S. Army Airborne School (USAAS). Students performed
      their first parachute jumps with the T-11 and subsequent jumps with the T-10.
      Injury data were collected from routine reports produced by the USAAS. Combat
      loaded jumps and night jumps were excluded from the analysis since these were
      only conducted with the T-10. RESULTS: There were a total of 76 injuries in
      30,755 jumps for an overall cumulative injury incidence of 2.5/1000 jumps. With
      the T-10 parachute, there were 61 injuries in 21,404 jumps for a cumulative
      injury incidence of 2.9/1000 jumps; with the T-11 parachute there were 15
      injuries in 9351 jumps for a cumulative injury incidence of 1.6/1000 jumps [risk
      ratio (T10/T11) = 1.78, 95% confidence interval = 1.01-3.12, P = 0.04].
      DISCUSSION: Limitations to this analysis included the fact that the T-11 was only
      used on the first jumps among students who had likely never previously performed
      a parachute jump and that aircraft exit procedures differed very slightly for the
      two parachutes. Nonetheless, the data suggest that injury incidence is lower with
      the T-11 parachute than with the T-10 parachute when airborne training operations
      are conducted during the day without combat loads.

PMID- 21961397
TI  - Dietary salt, bone strength, and mineral content in unloaded rat femurs.
AB  - INTRODUCTION: Reduced bone mineral and ultimate strength are regular consequences
      of unloading bone. The aim of this study was to determine if high dietary salt
      intake would reduce the bone density and strength to a greater extent in rats
      with unloaded bones compared to ambulatory control rats fed the same dietary
      calcium and phosphorus. METHODS: Mature male Sprague-Dawley rats were divided
      into four groups: two exposed to a spaceflight model that unloaded the hind limbs
      (HU) and two controls (C) with normal ambulation. Half the HU and C rats were fed
      normal dietary salt (0.26%, NNa) and half high dietary salt (8%, HNa). The
      calcium (Ca) and phosphorus (P) content of the diets was normal (Ca 0.5% and P
      0.6%) in all four groups. After 4 wk of hind limb unloading, the bone mineral
      content (BMC) of excised femurs was measured by the ash weight and the ultimate
      torsional strength was determined by a torsional strength test device. RESULTS:
      Femoral BMC (mg) was lower in HUNNa than C rats fed normal salt diets. Femurs
      from HU rats fed normal salt diets showed lower (20-26%) torsional strength
      (Nmm), compared to all other groups. DISCUSSION: It appears that high salt diets
      with normal amounts of calcium and phosphorus may prevent the decrease in bone
      torsional strength and BMC induced by unloading the femurs in 6-mo-old rats.

PMID- 21961398
TI  - Bronchial nitric oxide flux and alveolar nitric oxide concentration after
      exposure to hyperoxia.
AB  - BACKGROUND: The fraction of nitric oxide in exhaled gas (FE(NO)) is reduced by 30
      70% after exposure to partial pressures of oxygen (Po2) of 200-240 kPa for 90
      min. The purpose of this study was to partition FE(NO) into its flow-independent
      alveolar and bronchial components. A reduced bronchial NO flux (JawNO) is
      associated with induced bronchoconstriction, while increased alveolar NO
      concentration (C(A)NO) is associated with increased alveolar dead space. METHODS:
      There were 12 patients undergoing hyperbaric oxygen (HBO) therapy for 90 min at a
      Po2 of 240 kPa and 20 healthy subjects exposed to normobaric hyperoxia (NBO)
      breathing 100% oxygen for 90 min who were compared to a control group of 6
      subjects breathing ambient air. FE(NO) was measured at flow rates from 30 to 250
      ml x s(-1) before and after the exposures and the Hogman Marilainen algorithm was
      used to calculate JawNO and C(A)NO. RESULTS: FE(NO) at an expiratory flow rate of
      50 ml x s(-1) was reduced from 17.6 +/- 8.3 to 12.3 +/- 6.3 ppb after HBO
      exposure and from 17.8 +/- 6.2 to 13.3 +/- 5.2 ppb after NBO exposure. There was
      a significant reduction in JawNO, but unchanged C(A)NO. There were no changes in
      the control experiment. DISCUSSION: The reduction in FE(NO) after exposure to
      normobaric and hyperbaric hyperoxia appears to be predominantly an airway effect.
      An unchanged and low C(A)NO indicate preserved integrity of the gas exchange
      units without increased alveolar dead space at rest.

PMID- 21961399
TI  - Tactile cueing in detecting and controlling pitch and roll motion.
AB  - BACKGROUND: Tactile cueing has been explored primarily for the detection of
      linear motion such as vertical, longitudinal, and lateral translation in the
      laboratory and in flight. The usefulness of tactile cues in detecting roll and
      pitch motion has not been fully investigated. METHODS: There were 12 subjects (21
      56 yr) who were exposed to controlled pitch and roll motion generated by a motion
      platform with and without tactile cueing. The tactile system consists of a torso
      vest with 24 electromechanical tactors and a tactor on each shoulder and under
      each thigh harness, respectively. While devoid of visual and auditory cues, each
      subject performed three tasks: 1) indicate motion perception without tactile cues
      (C1); 2) return to vertical from an offset angle (C2); and 3) maintain straight
      and level while the platform was continuously in motion (C3). RESULTS: Our
      results indicated that in the absence of visual and auditory cues, subjects
      reported that the tactile system was useful in the execution of C2 and C3
      maneuvers. Specifically, the presence of tactile cues had a significant impact on
      the accuracy, duration, and perceived workload. In addition, tactile cueing also
      increased the accuracy in returning to neutral from an offset position and in
      maintaining the neutral position while the platform was in continuous motion.
      CONCLUSIONS: Tactile cueing appears to be effective in detecting roll and pitch
      motion and has the potential to reduce the workload and risks of high stress and
      time sensitive air operations.

PMID- 21961400
TI  - Off vertical axis rotation motion sickness and field dependence.
AB  - BACKGROUND: Our study probed the relationship between field dependence and the
      development of nausea in light and dark during whole-body, off vertical axis
      rotation (OVAR). METHODS: There were 24 subjects who underwent OVAR at 0.2 Hz, 18
      degree tilt. Exposures were undertaken in both light and darkness in sessions
      spaced 5 d apart in balanced order design. During rotation, nausea was rated at 1
      min intervals to a cut off at 20 min or a level of 'moderate nausea' was
      attained, at which point motion stopped. Before and after OVAR sessions field
      dependence was rated with the rod and frame test (RFT) with head upright or
      tilted 28 degree to induce a head-centric bias. RESULTS: Subjects tolerated OVAR
      longer in the light (mean 13.3 min +/- 6.8 SD) than in darkness (11.1 min +/-
      7.2). Motion sickness susceptibility evaluated by questionnaire was inversely
      correlated with tolerance of OVAR in the light. There was a tendency for subjects
      who were visual field dependent to fare better with OVAR in the light than in
      darkness. Subjects whose RFT estimates with head tilted tended to incline the
      visual vertical to the direction of head tilt better tolerated OVAR in darkness.
      DISCUSSION: The results suggest that susceptibility, as evaluated by
      questionnaires probing motion sickness experiences in daily life, is influenced
      by visual factors. Assessments of sensitivity to reference frames for
      orientation, either visual or ego-centered, show promise for markers of motion
      sickness susceptibility according to the visual surround rather than to absolute
      levels of susceptibility to motion sickness.

PMID- 21961401
TI  - Examining the nature of fear of flying.
AB  - BACKGROUND: The nature of fear of flying (FOF) is not well understood. It is
      commonly assumed to be a fear learned from flight-specific experiences. However,
      existing literature suggests that FOF is a manifestation of fears of other
      stimuli (e.g., heights) embedded in the flying situation, but not specific to it.
      This study compared the level of prediction of FOF attained from flight-specific
      conditioning experiences (specifically, classical conditioning experiences in
      direct, observational, and verbal modes) with the level of prediction attained
      from flight-embedded fears. METHODS: There were 109 university students who
      completed the Flight Anxiety Situations Questionnaire (FAS) and the Fear Survey
      Schedule, Version III (FSS) as well as demographic and flying experience
      questionnaires built for this study. RESULTS: All FOF measures were highly
      predicted by at least one flight-embedded fear. Conversely, conditioning
      experiences predicted only four of five FOF measures and this prediction was not
      strong. In general, conditioning experiences did not behave as in previous
      studies of conditioning and fear. DISCUSSION: The results suggest that FOF is
      based more on several flight-embedded innate fears than on learned fears. The
      implications of these results for FOF emergence and prevention are discussed.

PMID- 21961402
TI  - G-protection mechanisms afforded by the anti-G suit abdominal bladder with and
      without pressure breathing.
AB  - BACKGROUND: G protection afforded by the abdominal bladder of a pneumatic anti-G
      suit is usually attributed to counteraction of G-induced caudad displacement of
      the heart and pooling of blood in the abdominal veins. The study examined whether
      the abdominal bladder might provide G protection also via other mechanisms.
      METHODS: Each subject was exposed to +Gz loads while sitting relaxed, wearing a
      full-coverage anti-G suit modified to permit separate pressurization of the
      abdominal and leg bladders. In two experimental series (N = 8, N = 14), subjects
      were breathing at positive airway pressure (PPB); in a third series, five
      subjects were breathing at atmospheric airway pressure. Intrathoracic pressures
      were estimated by use of esophageal catheters. RESULTS: During PPB at high G
      loads, intrathoracic pressure was higher with than without the pressurized
      abdominal bladder. In 7 of the 14 subjects, basilar intrathoracic pressure
      exceeded airway pressure during PPB when the abdominal bladder was pressurized.
      The mean arterial pressure response at high G loads was higher in this subset of
      subjects (55 +/- 23 mmHg) than in the subjects in whom airway pressure exceeded
      intrathoracic pressure (41 +/- 27 mmHg). Without PPB at increased G load, the
      intrathoracic pressure gradient was higher with than without the pressurized
      abdominal bladder. DISCUSSION: During PPB, the abdominal bladder acts as an
      airway counterpressure, thereby facilitating pressure transmission from the
      airways to the thorax and hence improving G protection. It also appears that in
      several individuals, pressure may be transmitted from the abdominal bladder to
      the thorax and heart.

PMID- 21961403
TI  - Neck pain in military helicopter aircrew and the role of exercise therapy.
AB  - Neck pain is a growing aeromedical concern for military forces on an
      international scale. Neck pain prevalence in the global military helicopter
      community has been reported in the range of 56.6-84.5%. Despite this high
      prevalence, historically, research examining helicopter aircrews has focused
      predominantly on low back pain. A number of recent studies have emerged examining
      flight-related factors that are hypothesized to contribute to the development of
      flight-related neck pain. Loading factors such as the posture adopted during
      flight, use of night vision goggles, and vibration have all been found to
      contribute to neck pain and muscular fatigue. Prolonged or repeated exposureto
      these loading factors has been hypothesized to perpetuate or contribute to the
      development of neck pain. Despite the high number of helicopter aircrew personnel
      that suffer from neck pain, very few individuals seek treatment for the disorder.
      The focus of medical personnel should, therefore, be directed toward a solution
      that addresses not only the issue of muscular fatigue, but the hesitancy to seek
      treatment. Previous research in military and civilian populations have used
      exercise therapy as a treatment modality for neck pain and have found improved
      endurance capacity in the neck musculature and reduced self-reported neck pain.

PMID- 21961404
TI  - Pressure hyperalgesia in hind limb suspended rats.
AB  - INTRODUCTION: Spaceflight and simulated microgravity often associate with pain
      and prediabetes. Streptozotocin (STZ)-induced moderate insulinopenia rat models
      of prediabetes result in pressure hyperalgesia. The current study was designed to
      determine whether or not simulated microgravity induced by hind limb suspension
      (HLS) in rats lead to insulinopenia and pressure hyperalgesia. METHODS: Adult
      male rats were divided into HLS (N = 20) and control, non-suspended (N = 16)
      groups, respectively. Bodyweight and hind limb pressure-pain withdrawal threshold
      (PPT) were measured at regular 2-5 d intervals for 7 d before and 12-13 d after
      HLS. RESULTS: Bodyweights and PPT of control and HLS animals measured on the day
      of suspension were not different. During the experiment, control rats gained 61
      +/- 5 g, but maintained their PPT at the baseline level. Suspended rats gained 26
      +/- 3 g of weight during the same time period and their PPT declined from 105 +/-
      6 g to 84 +/- 6 g. Neither blood glucose nor pancreatic islet density and area
      were affected by HLS. However, the random plasma insulin of HLS rats was
      significantly lower than that of control animals (1.6 +/- 0.2 vs. 2.7 +/- 0.2 ng
      ml(-1)). DISCUSSION: The observed relationship between insulin and PPT levels in
      the HLS rats was similar to that observed in rats with STZ-induced insulinopenia.
      These data suggest that moderate insulinopenia may affect the rat's sensitivity
      to deep pressure directly, without affecting glucose homeostasis. In addition,
      our data suggest that HLS rats may develop peripheral neuropathy.

PMID- 21961405
TI  - Paranasal sinus mucosal hypertrophy in experienced divers.
AB  - INTRODUCTION: Due to the increasing popularity in recreational diving long-term
      health consequences of this sport have aroused interest in the diving community.
      Although not as important as dysbaric osteonecrosis, ischemic brain lesions, or
      neurophysiological symptoms, paranasal sinus mucosal hypertrophy (PSMH) has also
      been discussed as being more prevalent among divers. In this study, we used
      magnetic resonance imaging (MRI) to compare asymptomatic divers with control
      subjects for PSMH. METHODS: We enrolled 79 male divers (34.0 +/- 5.7 yr) and 79
      nondiving age- and sex-matched controls (33.8 +/- 6.1 yr). We used a
      questionnaire to elicit diving history. Divers with a history of sinus
      barotrauma, subjects with a history of chronic sinusitis or nasal allergies, and
      those with retention cysts, nasal polyps, or mastoiditis were excluded. T1-, T2
      weighted axial and coronal images of the paranasal sinuses were taken with a 1.5
      T MRI device. The threshold for PSMH was defined as mucosal thickness above 3 mm.
      RESULTS: MRI revealed PSMH in 33 (41.8%) divers and 18 (22.8%) controls. There
      were no significant differences between the groups with respect to age, smoking
      history, or alcohol consumption. PSMH identified in divers did not show an
      association with age or diving history. DISCUSSION: The higher rate of PSMH
      identified in divers suggests that diving may cause changes in the paranasal
      sinus mucosa.

PMID- 21961406
TI  - Cervical artery dissection following a turbulent flight.
AB  - BACKGROUND: Cervical artery dissection is a common cause of stroke in young
      patients without vascular risk factors and may affect the carotid or vertebral
      arteries. The risk of spontaneous dissection is higher in those with genetic
      predisposing factors while other cases may be precipitated by an event involving
      head or neck movement or associated with direct neck trauma. CASE REPORT: We
      present the case of a previously well young woman with a history of migraine who
      developed internal carotid artery dissection following a turbulent short-haul
      commercial flight while restrained using a seatbelt. DISCUSSION: We propose that
      repetitive flexion-hyperextension neck movements encountered during the flight
      were the most likely precipitant of carotid artery dissection in this case and
      review the therapeutic options available.

PMID- 21961407
TI  - Public health from space?

PMID- 21961409
TI  - This month in aerospace medicine history.

PMID- 21961408
TI  - You're the flight surgeon: Raynaud's disease.

PMID- 21961410
TI  - [Smoking among patients of selected specialist clinics of Miedzylesie Specialist
      Hospital in Warsaw].
AB  - The purpose of the study is to examine the issue of smoking among patients of
      selected clinics of the Miedzylesie Specialist Hospital in Warsaw, assessment of
      nicotine addiction of smokers and motivation to give up smoking. The survey was
      carried out in June and July 2009 after obtaining the consent of the Director of
      Miedzylesie Specialist Hospital in Warsaw. The survey was participated in by 100
      patients of selected specialist clinics. The survey was carried out on the basis
      of a questionnaire consisting of 7 questions. Furthermore, the "Test of
      motivation to give up smoking" (Schneider's test) and the "Assessment of nicotine
      addiction level" (Fagerstrom's test), published in the "Consensus regarding
      recognition and treatment of nicotine addiction", were used. When processing
      data, the descriptive statistics were applied. Those surveyed included 53 former
      cigarette smokers 47 active smokers and. In the group of former smokers, 19
      people still were exposed to passive smoking. In the past, the problem regarded
      41 people. Thirty former smokers smoked cigarettes among non-smokers, including
      young children (18 people) and when pregnant and breastfeeding (2 people). Also
      30 respondents smoked despite medical contraindications and bad conscience. For
      27 people, expenditures on cigarettes constituted a considerable burden of their
      respective household budgets, and 20 said that it was a significant item in their
      expenditures. Smokers have been smoking cigarettes for 30 years, on average 20
      cigarettes a day. Those patients began to smoke at the age of 20. Thirty one
      active smokers exposed other people to passive smoking and 38 respondents smoked
      cigarettes despite medical contraindications and with bad conscience. For 22
      people, expenditures related to smoking are a considerable burden of the
      household budget and for 21 people, it is a significant expenditure. Almost one
      half of the patients smoke cigarettes although they should brake off smoking for
      medical reasons. Most of those surveyed (32 people) are motivated to brake off
      smoking. Those people are highly (13 people) and extremely (9 people) addicted to
      nicotine.

PMID- 21961411
TI  - [Analysis of osteopontin in patients with acute pancreatitis].
AB  - The aim of this study was to analyze osteopontin (OPN) concentrations in patients
      with acute pancreatitis (AP) and its suitability for diagnosis and prediction of
      severity during the first 3 days from admission to hospital. The study group
      consisted of 40 patients admitted and hospitalized at I-st and II-nd Depatments
      of Surgery Jagiellonian University Collegium Medicum in Krakow. All laboratory
      tests necessary for diagnosis and monitoring of patients were performed in the
      Diagnostic Dept. of University Hospital, other immunochemistry parameters were
      assesed in the Diagnostic Dept. of Clinical Biochemistry Jagiellonian University
      using ELISA kits. The concentrations of OPN in severe acute pancreatitis were
      significantly higher than in patients with mild form of disease in the whole
      observation period. Simultaneously, we observed that increased in OPN
      concentrations in consecutive days of AP may be helpful in prediction of severity
      and compilations during AP.

PMID- 21961412
TI  - [ABL domain kinase point mutations as a cause of resistance to therapy of
      patients with chronic myeloid leukemia with tyrosine kinase inhibitors. Single
      center experience].
AB  - Introduction of tyrosine kinase inhibitors (TKIs) in the therapy of chronic
      myeloid leukemia have been significantly improved the results of the treatment
      and prognosis of CML patients. Despite of high efficacy of TKIs therapy,
      resistance is developing in substantial percentage of patients, which accounts
      for up to 40% after several years of treatment. There are several identified
      mechanisms of resistance to TKIs. The presence of ABL kinase domain point
      mutation, which could be detected by molecular methods is one of them. The aim of
      the study was to screen 60 CML patients resistant to TKI therapy for the presence
      of ABL point mutation. ABL mutation was detected in 19 (31,6%) patients. In four
      cases with detected mutation the disease has progressed to blast crisis.
      Investigation of ABL mutation occurrence can help in finding the cause of
      resistance to TKI therapy in some patients suffering from CML.

PMID- 21961413
TI  - [Beta-carotene regulates the expression of proapoptotic BAX and CAPN2 in HL-60, U
      937 and TF-1 - human acute myeloid leukemia cell lines; microarray, RQ-PCR and
      Western Blot analysis].
AB  - Beta carotene (BC) is a nutritional compound widespread in foods which can
      influence vital cellular functions--differentiation, proliferation and apoptosis
      of normal and cancer cells. However its role in the carcinogenesis remains
      controversial. We performed a microarray expression analysis in three human acute
      leukemia cell lines (HL-60, U937 and TF-1) exposed to 10mM BC and found that BC
      stimulated the apoptosis in all studied cell lines. This effect was most evident
      in the HL-60 cell line and correlated with increased expression of proapoptotic
      BAX and CAPN2 genes. The micro-array findings were replicated by the quantitative
      BAX and CAPN2 expression analysis using real-time PCR and by Western Blot on
      protein level. The biological tests (TUNEL method) for apoptosis showed
      consistent proapoptotic effects in all studied cell lines. In this paper the
      stimulatory effect of BC on apoptosis (enhanced expression of proapoptotic genes
      and proteins) in human acute myeloid leukemia cells was confirmed. The most
      potent activation of apoptosis in the HL-60 cells is in line with other
      investigators observations suggesting distinct molecular mechanism of apoptosis
      stimulation by BC in different human acute myeloid leukemia cells.

PMID- 21961414
TI  - [The concentration of HSP 27 in tumour and adjacent distal mucosa in colorectal
      adenocarcinoma].
AB  - OBJECTIVE: Heat shock proteins (HSPs) play a very important role in eukaryotic
      and prokaryotic cells. They are produced in cells constitutively or induced under
      stress conditions. During carcinogenesis, HSPs have been reported to show
      alteration of their expression levels. AIM OF THE STUDY: The aim of the study was
      assessment of the concentration of HSP 27 in tumour and adjacent distal normal
      mucosa in colorectal adenocarcinomas. MATERIAL AND METHODS: Samples of tumour
      tissues and adjacent distal normal colon tissues were obtained during resection
      operations from 47 patients aged between 26-82. Average distance of adjacent
      distal normal mucosa from the tumour was 4.49 cm. In tissues homogenate total
      protein level and concentration of HSP 27 were assayed. The patients were grouped
      according to clinical classification (Duke's staging), grade of differentiation,
      localization, and size of tumour, as well as age and sex. Relation between
      adjacent distal normal mucosa collected in different distances from the tumour
      and compared to concentration of HSP 27 was analyzed. Statistical analysis was
      performed. RESULTS: The concentration of HSP 27 was significantly increased in
      adjacent distal normal tissues compared with tumour tissues. Moreover, the
      concentration of HSP 27 was increased in adjacent normal tissues in patients with
      CD Duke's staging compared to patients with AB Duke's staging. No differences in
      concentration of HSP 27 between tumour and normal tissues compared with grade of
      differentiation, localization, and size oftumour, as well as age and sex were
      observed. No relation between adjacent distal normal mucosa collected in
      different distances from the tumour and compared to concentration of HSP 27 was
      observed. CONCLUSIONS: The higher concentration of HSP 27 in adjacent distal
      normal mucosa can be a response to stress factors related with metabolic changes
      of cancer tissues or can be a protective function to stress factors of the
      tumour.

PMID- 21961415
TI  - [Neurological and emotional profile of carpal tunnel syndrome patients].
AB  - Our aim was to define the type and frequency of symptoms in patients with
      neurophysiologically confirmed carpal tunnel syndrome (CTS). We also assessed the
      incidence of anxiety and depression in CTS and control group. MATERIAL AND
      METHODS: After carrying out neurophysiologic examination 87 patients were
      diagnosed with CTS, 50 patients without confirmed CTS diagnosis served as a
      control group. All patients underwent thorough neurological examination and
      completed a questionnaire about severity and localization of their symptoms.
      State-Trait Anxiety Inventory (STAI), Self Rating Anxiety Scale (SAS) and Beck's
      depression inventory were also filled in by the patients. RESULTS: In CTS
      patients major symptoms were: paresthesias and nocturnal aggravation of symptoms;
      pain was predominant sign in control group. There were no statistically
      significant differences between CTS patients and control group concerning
      emotional (depression and anxiety) disturbances. In CTS patients depression and
      anxiety were correlated with: diminished sensation, hand weakness, thenar atrophy
      and hand pain. CONCLUSIONS: Emotional disturbances appear to be linked with
      objective CTS symptoms and with pain and they increase with carpal tunnel
      syndrome intensity.

PMID- 21961416
TI  - [The risk factors in elderly intensive care unit (ICU) patients admitted after
      non-traumatic haemorrhagic shock].
AB  - Haemorrhage into the digestive tract lumen in elderly patients leads directly to
      multiorgan instability and failure. Analysis of 68 ICU patients, treated in 2007
      2008 proved interdependence between presenting co-existing diseases, including
      reduction of vital organ reserve, and multiorgan dysfunction. Each patient was
      evaluated consecutively according to four commonly accepted severity-of-illness
      scoring systems (severity models): SAPS2, LODS, MODS and POSSUM. The assessment
      was displayed in numbers (predicted death rate, PDR) and in binary system of
      survivors (60%) and non-survivors (40%). The last group was divided into two
      subgroups: a/. those, who survived (their average PDR calculated in SAPS 2 on
      admittance was 22.3 vs after surgery on ICU was 25.1, and respectively computed
      in LODS on admittance was 17.4 vs after surgery on ICU was 21.4), and b/. those,
      who died shortly after hospital admittance, or following surgery in the ICU
      (their average PDR calculated on admittance in SAPS2 was 34.8 vs after surgery on
      ICU was 62.3, and respectively computed in LODS on admittance was 30.0 vs after
      surgery on ICU was 57.2). In POSSUM average PDR calculated for survivors was 61.6
      vs for 85.4 in non-survivors. The difference was also noticed during collecting
      points in severity scoring systems: in MODS for non-survivors (3.3 on admittance
      vs 7.5 calculated in ICU after surgery), and in LODS (5.8 vs 9.5, respectively),
      p<0.001. The main risk factors were systolic blood pressure < 90 mmHg, HR >
      140/min, Glasgow Coma Scale < 12, urine output < 20ml/ h, Hb < 8.5 g/L,
      creatinine > 350 micromol/l, paO2 < 60 mmHg, INR > 2,2, catecholamine i.v.
      administration > 1 h, mechanical ventilation > 48h, surgery < 2h following
      patients hospital admittance. In non-survivor group there were more than two co
      existing diseases in the 3rd or 4th degree of advancement (p<0.004).

PMID- 21961417
TI  - [Perioperative antibiotic prophylaxis in surgery].
AB  - Surgical site infections - SSI belong to one of the most frequent and serious
      post-operative complications occurring in patients. They lead to extended
      hospitalization period, to increase of treatment costs, morbidity and mortality
      among patients. The surgical antibiotic prophylaxis is one of the most
      significant procedures which goal is to reduce infectious complications and to
      complement surgical effects. Proper surgical antibiotic prophylaxis should be
      distinguished by: appropriate time of application and administration adequate to
      the kind of treatment and quality of the drug, proper selection of the antibiotic
      which considers microbiological as well as pharmacological conditions which has
      established clinical effectiveness.

PMID- 21961418
TI  - [The role of thyroid antibodies in the pathogenesis of the infertility and
      miscarriage].
AB  - There are discordant opinions about the influence of subclinical hypothyroidism
      to the fertility of the women. No unequivocal opinion has been presented
      concerning the purposefulness of the diagnostics process and treatment of the
      pregnant women with subclinical hypothyroidism. Few clinical studies suggest that
      there is a connection between thyroid antibodies and infertility, spontaneous
      miscarriages, implantation failures and fetal malformations.

PMID- 21961419
TI  - [Jan Mikulicz-Radecki (1850-1905)--a worldwide known surgeon, a head of Surgical
      Department in Wroclaw (1890-1905), his historical view, on his 105 death
      anniversary].

PMID- 21961420
TI  - [Ludwik Rydygier (1850-1920)--one of the most prominent surgeons of his times. On
      the occasion of his 90th death anniversary].

PMID- 21961421
TI  - Enablement: can we ever be too kind?

PMID- 21961422
TI  - Close the loops: how to avoid the problems of loose ends.

PMID- 21961423
TI  - Disarmed: an unexpected amputation rattles more than just its victim.

PMID- 21961424
TI  - The managing EMS officer: managers often get a bad rap, but without them, where
      would we be?

PMID- 21961425
TI  - The nervous system: conditions involving the nervous system can present in many
      different ways.
AB  - Vertigo is a fairly common complaint encountered by medics. It is very upsetting
      and unpleasant for the patient, but it is usually benign and resolves on its own.
      However, it is vital that the medic be able to differentiate between common
      vertigo and a more serious condition like stroke. Careful attention to history
      and physical exam will allow medics to make the right determinations.

PMID- 21961426
TI  - A decade of remembrance: Top EMS leaders look back on the decade since 9/11--and
      what the future holds.

PMID- 21961427
TI  - To tube or not to tube? Does paramedical prehospital endotracheal intubation do
      more harm than good?

PMID- 21961428
TI  - Get a clue: It can be all too easy to make assessment errors in the field; here's
      some tips to prevent you from making mistakes.

PMID- 21961430
TI  - Above and beyond: Meet the recipients of the 2011 National EMS Awards.

PMID- 21961429
TI  - The challenge of in-flight emergencies: do you know what tools you'll have at
      your disposal?

PMID- 21961431
TI  - Legacy in the dust: On 9/11, the need to help trumped personal safety--the costs
      came later.

PMID- 21961434
TI  - Liquid structure of and Li+ ion solvation in bis(trifluoromethanesulfonyl)amide
      based ionic liquids composed of 1-ethyl-3-methylimidazolium and N-methyl-N
      propylpyrrolidinium cations.
AB  - Liquid structures of the bis(trifluoromethanesulfonyl)amide based ionic liquids
      composed of 1-ethyl-3-methylimidazolium and N-methyl-N-propylpyrrolidinium
      ([C(2)mIm(+)][TFSA(-)] and [C(3)mPyrro(+)][TFSA(-)], respectively) and Li(+) ion
      solvation structure in their lithium salt solutions were studied by means of high
      energy X-ray diffraction (HEXRD) technique with the aid of MD simulations. With
      regard to neat ionic liquids, a small but significant difference was found at
      around 3.5 A in the intermolecular radial distribution functions G(inter)(r)s for
      these two ionic liquids; i.e., G(inter)(r) for [C(2)mIm(+)][TFSA(-)] was
      positioned at a slightly shorter region relative to that for
      [C(3)mPyrro(+)][TFSA(-)], which suggests that the nearest neighboring cation
      anion interaction in the imidazolium ionic liquid is slightly greater than that
      in the other. With regard to Li(+) ion solvation structure, G(inter)(r)s for
      [C(2)mIm(+)][TFSA(-)] dissolving Li(+) ion exhibited additional small peak of
      about 1.9 A attributable to the Li(+)-O (TFSA(-)) atom-atom correlation, though
      the corresponding peak was unclear in [C(3)mPyrro(+)][TFSA(-)] due to overlapping
      with the intramolecular atom-atom correlations in [C(3)mPyrro(+)]. In addition,
      the long-range density fluctuation observed in the neat ionic liquids diminished
      with the increase of Li(+) ion concentration for both ionic liquid solutions.
      These observations indicate that the large scale Li(+) ion solvated clusters are
      formed in the TFSA based ionic liquids, and well support the formation of
      [Li(TFSA)(2)](+) cluster clarified by previous Raman spectroscopic studies. MD
      simulations qualitatively agree with the experimental facts, by which the
      decrease in the long-range oscillation amplitude of r(2){G(r) - 1} for the Li(+)
      containing ionic liquids can be ascribed to the variation in the long-range anion
      anion correlations caused by the formation of the Li(+) ion solvated clusters.

PMID- 21961433
TI  - Quantitative bone marrow lesion size in osteoarthritic knees correlates with
      cartilage damage and predicts longitudinal cartilage loss.
AB  - BACKGROUND: Bone marrow lesions (BMLs), common osteoarthritis-related magnetic
      resonance imaging findings, are associated with osteoarthritis progression and
      pain. However, there are no articles describing the use of 3-dimensional
      quantitative assessments to explore the longitudinal relationship between BMLs
      and hyaline cartilage loss. The purpose of this study was to assess the cross
      sectional and longitudinal descriptive characteristics of BMLs with a simple
      measurement of approximate BML volume, and describe the cross-sectional and
      longitudinal relationships between BML size and the extent of hyaline cartilage
      damage. METHODS: 107 participants with baseline and 24-month follow-up magnetic
      resonance images from a clinical trial were included with symptomatic knee
      osteoarthritis. An 'index' compartment was identified for each knee defined as
      the tibiofemoral compartment with greater disease severity. Subsequently, each
      knee was evaluated in four regions: index femur, index tibia, non-index femur,
      and non-index tibia. Approximate BML volume, the product of three linear
      measurements, was calculated for each BML within a region. Cartilage parameters
      in the index tibia and femur were measured based on manual segmentation. RESULTS:
      BML volume changes by region were: index femur (median [95% confidence interval
      of the median]) 0.1 cm3 (-0.5 to 0.9 cm3), index tibia 0.5 cm3 (-0.3 to 1.7 cm3),
      non-index femur 0.4 cm3 (-0.2 to 1.6 cm3), and non-index tibia 0.2 cm3 (-0.1 to
      1.2 cm3). Among 44 knees with full thickness cartilage loss, baseline tibia BML
      volume correlated with baseline tibia full thickness cartilage lesion area (r =
      0.63, p< 0.002) and baseline femur BML volume with longitudinal change in femoral
      full thickness cartilage lesion area (r = 0.48 p< 0.002). CONCLUSIONS: Many
      regions had no or small longitudinal changes in approximate BML volume but some
      knees experienced large changes. Baseline BML size was associated to longitudinal
      changes in area of full thickness cartilage loss.

PMID- 21961439
TI  - Hearing impairment and cognitive function among a community-dwelling population
      in Japan.
AB  - BACKGROUND: Hearing impairment is a prevalent and chronic condition in older
      people. This study investigated the relationship between cognitive function and
      hearing impairment in a Japanese population. METHODS: A pure-tone average (0.5
      2.0 kHz) was used to evaluate hearing impairment in 846 participants of the Iwaki
      Health Promotion Project who were aged at least 50 years old (310 men and 536
      women). We also administered the Mini-Mental State Examination (MMSE), the Center
      for Epidemiologic Studies for Depression (CES-D) scale, Starkstein's apathy scale
      (AS) and the Short Form Health Survey Version 2 (SF-36v2). A multiple linear
      regression analysis assessed the association between hearing impairment and
      mental correlates. RESULTS: The overall prevalence of hearing impairment in this
      study population was 37.7%. The participants with hearing impairment were older
      and less educated compared to those with no hearing problems. We observed
      significant differences in the MMSE and AS scores between the mild/moderate to
      severe groups versus the non-impaired group. After adjusting for age, gender and
      amount of education, hearing impairment was significantly associated with MMSE
      and AS scores, but not with CES-D scores. Hearing impairment was significantly
      related to the social functioning (SF) and role emotional (RE) scores of the SF
      36v2. CONCLUSIONS: Hearing impairment is common among older people and is
      associated with cognitive impairment, apathy and a poor health-related quality of
      life. Screening for and correcting hearing impairments might improve the quality
      of life and functional status of older patients.

PMID- 21961440
TI  - Anti-inflammatory activities of Reynoutria elliptica through suppression of
      mitogen-activated protein kinases and nuclear factor-kappaB activation pathways.
AB  - Reynoutria elliptica has been used in traditional Korean medicine to promote
      blood circulation, relieve pain, increase dieresis, and alleviate respiratory
      problems, through as yet undefined mechanisms. We set out to determine whether
      the anti-inflammatory effects of this plant are linked with its ability to
      suppress mitogen-activated protein kinases (MAPKs) and nuclear factor-kappaB (NF
      kappaB) activation in lipopolysaccharide (LPS)-activated RAW 264.7 cells. We
      found for the first time that the hexane fraction of Reynoutria elliptica (HRE)
      significantly inhibited LPS-stimulated NO and PGE2 synthesis. This is due to the
      diminishing of the mRNA and protein expression of iNOS and COX-2, respectively.
      HRE also suppressed LPS-stimulated TNF-alpha secretion in a dose-dependent
      manner, which might be due to the suppression of LPS-induced MAPKs and NF-kappaB
      activation. Moreover, our HPLC data demonstrated that the major components of the
      HRE were bioactive compounds such as emodin-6-Glc, emodin, and physcion. Overall,
      our results indicate that Reynoutria elliptica could be provided as a potential
      candidate for anti-inflammation treatment.

PMID- 21961441
TI  - Efficacy of constraint-induced movement therapy and electrical stimulation on
      hand function of children with hemiplegic cerebral palsy: a controlled clinical
      trial.
AB  - PURPOSE: The purpose of this study is to compare the efficacy of constraint
      therapy, constraint therapy plus electrical stimulation, and occupational therapy
      in the treatment of hand dysfunction. METHODS: Sixty-eight children with
      hemiplegic cerebral palsy were randomly allocated to constraint therapy,
      constraint therapy plus electrical stimulation, and occupational therapy group.
      Three groups received 2 weeks of treatment. All participants were measured at
      baseline and 2 weeks, 3 and 6 months after treatment using measures of active
      ROM, grip strength, nine-peg hole test, upper extremity functional test, Peabody
      developmental motor scales (PDMS), globe rating scale, and social life ability
      scale. RESULTS: Three groups improved significantly (p < 0.05). The mean
      improvements between baseline and the end of follow-up were respectively 12.4,
      11.4 and 11.3 degrees for active ROM; 12.8, 10.5 and 8.8 mmHg for grip strength; 
      22.3, -30.7 and -14.0 s for nine-peg hole test; 15.3, 10.3 and 10.4 for upper
      extremity functional test scores; 2.2, 1.8 and 1.8 for grasping scores of PDMS;
      5.8, 3.7 and 2.8 for visual-motor integration scores of PDMS; 2.0, 2.5 and 0.9
      for globe rating scale scores; 7.7, 5.7 and 5.3 for social life ability scale
      scores in constraint therapy plus electrical stimulation, constraint therapy, and
      occupational therapy group. The constraint therapy plus electrical stimulation
      group showed greater rate of improvement in upper extremity functional test
      scores (p < 0.05) and visual-motor integration scores of PDMS (p < 0.05) than the
      other two groups after treatment for 6 months. CONCLUSIONS: Constraint therapy
      plus electrical stimulation is likely to be best in improving hand performance in
      children with hemiplegic cerebral palsy.

PMID- 21961442
TI  - Beliefs about women's vibrator use: results from a nationally representative
      probability survey in the United States.
AB  - Women's vibrator use is common in the United States, although little is known
      about beliefs about its use. Elicitation surveys and interviews informed the
      development of a 10-item scale, the Beliefs About Women's Vibrator Use Scale,
      which was administered to a nationally representative probability sample of
      adults ages 18 to 60 years. Most women and men held high positive and low
      negative beliefs about women's vibrator use. Women with positive beliefs reported
      higher Female Sexual Function Index scores related to arousal, lubrication,
      orgasm, satisfaction, and pain (indicating less pain).

PMID- 21961443
TI  - Should we take anodyspareunia seriously? A descriptive analysis of pain during
      receptive anal intercourse in young heterosexual women.
AB  - Anal sex is becoming increasingly prevalent among heterosexual women and men.
      Although pain related to receptive anal intercourse is not uncommon, little is
      known about its phenomenology. This article aims to assess the prevalence and
      correlates of pain during anoreceptive intercourse, including anodyspareunia, its
      most severe form, among young women. An online survey focusing on anal eroticism
      was carried out in March and April 2010 on a convenience sample of 2,002 women 18
      30 years of age. Participants who reported 2 or more episodes of anal intercourse
      in the past year were asked about the level and frequency of pain at anoreceptive
      penetration; those who reported unbearable (too painful to continue) or strong
      pain at every such occasion were classified as anodyspareunic. The experience of
      receptive anal intercourse was reported by 63.2% (n = 1,265) of participants.
      Although almost half (48.8%) had to discontinue their first anoreceptive
      intercourse because of pain or discomfort, a majority of women (62.3%; n = 788)
      continued anal sex. Of the 505 participants who reported 2 or more episodes of
      anal intercourse in the past year, the women (8.7%; n = 44) who reported severe
      pain during every anoreceptive penetration were classified as anodyspareunic; all
      others were classified as non-anodyspareunic. For more than two thirds of women
      with anodyspareunia, the current pain level remained unchanged from their first
      experience with anal sex. Inability to relax was the most frequent self
      hypothesized cause of pain among the anodyspareunic and nonanodyspareunic groups.
      Compared with other women, those with anodyspareunia reported substantially lower
      levels of sexual satisfaction (odds ratio = .95; p < .001) and were less sexually
      assertive (odds ratio = .80; p < .01). The findings that a substantial proportion
      of women reported pain at first and subsequent anoreceptive intercourse highlight
      a need for more information and education about anal eroticism.

PMID- 21961444
TI  - Reliability, validity, and psychometric development of the pornography
      consumption inventory in a sample of hypersexual men.
AB  - This article reports the psychometric evaluation of the Pornography Consumption
      Inventory (PCI), which was developed to assess motivations for pornography use
      among hypersexual men. Initial factor structure and item analysis were conducted
      in a sample of men (N = 105) seeking to reduce their pornography consumption
      (Study 1), yielding a 4-factor solution. In a second sample of treatment-seeking
      hypersexual men (N = 107), the authors further investigated the properties of the
      PCI using confirmatory factor analytic procedures, reliability indices, and
      explored PCI associations with several other constructs to establish convergent
      and discriminant validity. These studies demonstrate psychometric evidence for
      the PCI items that measure tendencies of hypersexual men to use pornography (a)
      for sexual pleasure; (b) to escape, cope, or avoid uncomfortable emotional
      experiences or stress; (c) to satisfy sexual curiosity; and (d) to satisfy
      desires for excitement, novelty, and variety.

PMID- 21961445
TI  - Relationship among sexual desire, sexual satisfaction, and quality of life in
      middle-aged and older adults.
AB  - The authors examined the association among sexual desire, sexual satisfaction,
      and quality of life in a sample of community participants. They predicted that
      quality of life would be positivity correlated with sexual satisfaction and that
      sexual desire would indirectly influence quality of life. This research showed
      that elderly adults' sexual desire and sexual satisfaction decrease with age and
      that nearly 40% of the interviewees still had sexual activity one or more times
      every month. The results revealed that sexual desire does not directly influence
      quality of life, but it does have a direct effect on sexual satisfaction; hence,
      sexual satisfaction will indirectly affect quality of life.

PMID- 21961446
TI  - A longitudinal study of attempted religiously mediated sexual orientation change.
AB  - The authors conducted a quasi-experimental longitudinal study spanning 6-7 years
      examining attempted religiously mediated sexual orientation change from
      homosexual orientation to heterosexual orientation. An initial sample was formed
      of 72 men and 26 women who were involved in a variety of Christian ministries,
      with measures of sexual attraction, infatuation and fantasy, and composite
      measures of sexual orientation and psychological distress, administered
      longitudinally. Evidence from the study suggested that change of homosexual
      orientation appears possible for some and that psychological distress did not
      increase on average as a result of the involvement in the change process. The
      authors explore methodological limitations circumscribing generalizability of the
      findings and alternative explanations of the findings, such as sexual identity
      change or adjustment.

PMID- 21961447
TI  - Perception of partner sleep and mood: postpartum couples' relationship
      satisfaction.
AB  - Separate research areas indicate that sleep quality, mood, and relationship
      satisfaction decline among couples during the postpartum period. Furthermore,
      accurate partner perceptions are associated with positive relationship qualities.
      In this study, 21 first-time postpartum mother-father dyads, contributed 1 week
      of continuous wrist actigraphy along with concurrent subjective Palm Pilot
      monitoring to provide objective and subjective sleep measures. Parents also
      reported on their own as well as their perception of their partners' sleep, mood,
      and relationship satisfaction. Greater objectively measured total sleep time was
      associated with greater relationship satisfaction. Mothers (a) underestimated
      fathers' self-reported frequency of nocturnal awakenings, as well as (b)
      relationship satisfaction, and (c) overestimated fathers' self-reported sleep
      quality. Fathers (a) underestimated mothers' self-reported duration of wake at
      night, as well as (b) sleep quality, and (c) overestimated mothers' self-reported
      mood disturbance. Preventative measures that target sleep and improvement in
      perception of partner's experiences could be used to buffer against decreases in
      relationship satisfaction among new parents.

PMID- 21961454
TI  - Tissue integration of a new titanium-zirconium dental implant: a comparative
      histologic and radiographic study in the canine.
AB  - BACKGROUND: This study evaluates a newly developed titanium-zirconium implant
      (TiZr), comparing it to a commercially available pure titanium (Ti) implant
      subjected to the same surface treatment. METHODS: In nine dogs, 12 implants (six
      TiZr and six Ti) were randomly placed in the mandible with the implant shoulder
      at the bone crest and subjected to submerged healing. Standardized radiographs
      were taken after implantation, and at the sacrifice of 2 weeks (three dogs), 4
      weeks (three dogs), and 8 weeks (three dogs). Histologic and histomorphometric
      measurements were performed on non-decalcified histologic sections. The main
      outcome measures included the first bone-implant contact (fBIC) and BIC over
      time. For statistical analysis, Wilcoxon signed-rank test and mixed model
      regressions were applied. RESULTS: From baseline to 8 weeks, a mean bone loss of
      0.09 +/- 0.33 mm for TiZr and a gain of 0.02 +/- 0.33 mm for Ti were calculated
      radiographically. The number of implants with the fBIC coronal to the reference
      point (implant shoulder) gradually increased over time, reaching 39% of all TiZr
      implants and 50% of all Ti implants at 8 weeks. The mean fBIC values for Ti and
      TiZr were 0.29 +/- 0.42 mm and 0.26 +/- 0.32 mm (2 weeks), -0.01 +/- 0.20 mm and
      0.10 +/- 0.28 mm (4 weeks), and -0.06 +/- 0.22 mm and 0.08 +/- 0.30 mm (8 weeks),
      respectively. The mean BIC values peaked at 86.9% +/- 6.8% (8 weeks) for TiZr and
      at 83.4% +/- 5.9% (4 weeks) for Ti. No statistically significant differences were
      observed at any time point. CONCLUSION: TiZr and Ti bone level implants with
      chemically-modified, sandblasted, and acid-etched surfaces performed similarly in
      regards to osseointegration in this unloaded canine study.

PMID- 21961455
TI  - Arthroscopic washout of the ankle for septic arthritis in a three-month-old boy.
AB  - There is no report of athroscopic treatment for septic arthritis of the ankle in
      infants. We report a case of successful management of septic arthritis of the
      ankle in a three-month-old boy by arthroscopic washout. Arthroscopic washout may
      be a useful treatment for septic arthritis in young infants when performed early
      after onset.

PMID- 21961457
TI  - Solvent-free cross-dehydrogenative coupling reactions under high speed ball
      milling conditions applied to the synthesis of functionalized
      tetrahydroisoquinolines.
AB  - Solvent-free reaction using a high-speed ball milling technique has been first
      applied to cross-dehydrogenative coupling (CDC) reactions between
      tetrahydroisoquinolines and three types of pronucleophiles such as nitroalkanes,
      alkynes, and indoles. All coupling products were obtained in good yields at short
      reaction times (no more than 40 min). When alkynes and indoles were used as
      pronucleophile, the reactions can be catalyzed efficiently by recoverable copper
      balls without any additional metal catalyst.

PMID- 21961456
TI  - Comparison of PCR ribotyping and multilocus variable-number tandem-repeat
      analysis (MLVA) for improved detection of Clostridium difficile.
AB  - BACKGROUND: Polymerase chain reaction (PCR) ribotyping is one of the globally
      accepted techniques for defining epidemic clones of Clostridium difficile and
      tracing virulence-related strains. However, the ambiguous data generated by this
      technique makes it difficult to compare data attained from different
      laboratories; therefore, a portable technique that could supersede or supplement
      PCR ribotyping should be developed. The current study attempted to use a new
      multilocus variable-number tandem-repeat analysis (MLVA) panel to detect PCR
      ribotype groups. In addition, various MLVA panels using different numbers of
      variable-number tandem-repeat (VNTR) loci were evaluated for their power to
      discriminate C. difficile clinical isolates. RESULTS: At first, 40 VNTR loci from
      the C. difficile genome were used to screen for the most suitable MLVA panel.
      MLVA and PCR ribotyping were implemented to identify 142 C. difficile isolates.
      Groupings of serial MLVA panels with different allelic diversity were compared
      with 47 PCR-ribotype groups. A MLVA panel using ten VNTR loci with limited
      allelic diversity (0.54-0.83), designated MLVA10, generated groups highly
      congruent (98%) with the PCR-ribotype groups. For comparison of discriminatory
      power, a MLVA panel using only four highly variable VNTR loci (allelic diversity:
      0.94-0.96), designated MLVA4, was found to be the simplest MLVA panel that
      retained high discriminatory power. The MLVA10 and MLVA4 were combined and used
      to detect genetically closely related C. difficile strains. CONCLUSIONS: For the
      epidemiological investigations of C. difficile, we recommend that MLVA10 be used
      in coordination with the PCR-ribotype groups to detect epidemic clones, and that
      the MLVA4 could be used to detect outbreak strains. MLVA10 and MLVA4 could be
      combined in four multiplex PCR reactions to save time and obtain distinguishable
      data.

PMID- 21961462
TI  - Smoking-cessation prevalence among U.S. smokers of menthol versus non-menthol
      cigarettes.
AB  - BACKGROUND: The Food and Drug Administration currently is assessing the public
      health impact of menthol cigarettes. Whether menthol cigarettes pose increased
      barriers to quitting is a critical issue because previous declines in smoking
      prevalence have stalled. PURPOSE: To explore whether menthol cigarette smokers
      are less likely to quit than non-menthol smokers at the population level and
      whether this relationship differs by race/ethnicity. METHODS: Cross-sectional
      analyses of the 2003 and 2006/2007 Tobacco Use Supplement to the Current
      Population Survey were conducted in 2010. Multiple logistic regressions were used
      to calculate the adjusted odds of cessation for menthol smoking relative to non
      menthol smoking. Five different sample restrictions were used to assess the
      robustness of the findings. RESULTS: In the broadest sample restriction, menthol
      smokers were less likely to have quit smoking (AOR=0.91, 95% CI=0.87, 0.96). This
      relationship holds among whites (AOR=0.93, 95% CI=0.88, 0.98) and blacks
      (AOR=0.81, 95% CI=0.67, 0.98). The magnitude of the relationship among Hispanics
      was similar to that among whites, but differed by Hispanic origin. Among those of
      Mexican origin, the AOR for menthol smokers was protective but not significant
      (AOR=1.29, 95% CI=0.99, 1.61), whereas among those of Puerto Rican origin,
      menthol smokers were less likely to have quit (AOR=0.57, 95% CI=0.37, 0.87).
      These findings were robust and significant in four of five sample restrictions.
      CONCLUSIONS: Smoking menthol cigarettes is associated with decreased cessation at
      the population level, and this association is more pronounced among black and
      Puerto Rican smokers. These findings support the recent calls to ban menthol
      flavoring in cigarettes.

PMID- 21961463
TI  - Dietary weight loss and exercise effects on insulin resistance in postmenopausal
      women.
AB  - BACKGROUND: Comprehensive lifestyle interventions are effective in preventing
      diabetes and restoring glucose regulation; however, the key stimulus for change
      has not been identified and effects in older individuals are not established. The
      aim of the study was to investigate the independent and combined effects of
      dietary weight loss and exercise on insulin sensitivity and restoration of normal
      fasting glucose in middle-aged and older women. DESIGN: Four-arm RCT, conducted
      between 2005 and 2009 and data analyzed in 2010. SETTING/PARTICIPANTS: 439
      inactive, overweight/obese postmenopausal women. INTERVENTIONS: Women were
      assigned to: dietary weight loss (n=118); exercise (n=117); exercise+diet
      (n=117); or control (n=87). The diet intervention was a group-based reduced
      calorie program with a 10% weight-loss goal. The exercise intervention was 45
      min/day, 5 days/week of moderate-to-vigorous intensity aerobic activity. MAIN
      OUTCOME MEASURES: 12-month change in serum insulin, C-peptide, fasting glucose,
      and whole body insulin resistance (HOMA-IR). RESULTS: A significant improvement
      in HOMA-IR was detected in the diet (-24%, p<0.001) and exercise+ diet (-26%,
      p<0.001) groups but not in the exercise (-9%, p=0.22) group compared with
      controls (-2%); these effects were similar in middle-aged (50-60 years) and older
      women (aged 60-75 years). Among those with impaired fasting glucose (5.6-6.9
      mmol/L) at baseline (n=143; 33%), the odds (95% CI) of regressing to normal
      fasting glucose after adjusting for weight loss and baseline levels were 2.5
      (0.8, 8.4); 2.76 (0.8, 10.0); and 3.1 (1.0, 9.9) in the diet, exercise+diet, and
      exercise group, respectively, compared with controls. CONCLUSIONS: Dietary weight
      loss, with or without exercise, significantly improved insulin resistance. Older
      women derived as much benefit as did the younger postmenopausal women. TRIAL
      REGISTRATION: This study is registered at Clinicaltrials.govNCT00470119.

PMID- 21961464
TI  - Physical activity across adulthood and physical performance in midlife: findings
      from a British birth cohort.
AB  - BACKGROUND: Evidence, mainly from cross-sectional studies, suggests that physical
      activity is a potentially important modifiable factor associated with physical
      performance and strength in older age. It is unclear whether the benefits of
      physical activity accumulate across life or whether there are sensitive periods
      when physical activity is more influential. PURPOSE: To examine the associations
      of leisure-time physical activity across adulthood with physical performance and
      strength in midlife, and to test whether there are cumulative benefits of
      physical activity. METHODS: Using data on approximately 2400 men and women from
      the UK Medical Research Council National Survey of Health and Development,
      followed up since birth in March 1946, the associations of physical activity
      levels during leisure time self-reported prospectively at ages 36, 43, and 53
      years with grip strength, standing balance, and chair rise times, assessed by
      nurses at age 53 years (in 1999), were examined in 2010. RESULTS: There were
      independent positive effects of physical activity at all three ages on chair rise
      performance, and at ages 43 and 53 years on standing balance performance, even
      after adjusting for covariates. These results were supported by evidence of
      cumulative effects found when using structured life course models. Physical
      activity and grip strength were not associated in women and, in men, only
      physical activity at age 53 years was associated with grip strength. CONCLUSIONS:
      There are cumulative benefits of physical activity across adulthood on physical
      performance in midlife. Increased activity should be promoted early in adulthood
      to ensure the maintenance of physical performance in later life.

PMID- 21961465
TI  - Lay health educators translate a weight-loss intervention in senior centers: a
      randomized controlled trial.
AB  - BACKGROUND: Older adults have high obesity rates and respond well to evidence
      based weight-loss programs, such as the Diabetes Prevention Program (DPP)
      Lifestyle intervention. The goal of this study was to determine whether a
      translation of the DPP Lifestyle program delivered by lay health educators and
      conducted in senior centers is effective in promoting weight loss among older
      adults. DESIGN: An RCT with older adults nested within senior centers. Senior
      centers identified lay health educators to receive training and deliver the
      intervention program at the senior center. Senior centers were randomized to DPP
      Lifestyle program or an attention control intervention (cognitive training).
      SETTING/PARTICIPANTS: Senior centers (N=15) located throughout Arkansas.
      Participants (N=228) were obese (BMI=34.5+/-4.9) older (aged 71.2+/-6.6 years)
      adults able to engage in moderate exercise. Follow-up data were collected at 4
      months on 93% of the original cohort between February 2009 and July 2010.
      INTERVENTIONS: A 12-session translation of the Diabetes Prevention Program
      Lifestyle behavioral weight-control program delivered in group sessions by
      trained lay health educators. MAIN OUTCOME MEASURES: Body weight was assessed by
      digital scale. Percentage weight loss from baseline and proportion achieving >=5%
      and >=7% weight loss were examined. Analyses were completed in March 2011.
      RESULTS: Participants attending senior centers randomized to Lifestyle lost a
      significantly greater percentage of baseline weight (3.8%, 95% CI=2.9%, 4.6%)
      than those in the control senior centers (0.2%, 95% CI= -0.6%, -0.9%) after
      adjusting for baseline BMI and gender (p<0.001). Among participants attending
      senior centers offering the Lifestyle program, 38% lost >=5% of baseline weight
      compared with 5% in the control arm (p<0.001). Similarly, significantly more
      participants (24%) in Lifestyle senior centers lost >=7% than did control
      participants (3%, p=0.001). CONCLUSIONS: A behavioral lifestyle weight-loss
      intervention delivered by a lay health educator offers a promising vehicle for
      translation of evidence-based obesity treatment programs in underserved areas.
      TRIAL REGISTRATION: This study is registered at Clinicaltrials.govNCT01377506.

PMID- 21961466
TI  - A nutrition and physical activity intervention for family child care homes.
AB  - BACKGROUND: Family child care homes (FCCHs) provide child care to 1.9 million
      children in the U.S., but many do not meet established child care standards for
      healthy eating and physical activity. PURPOSE: To determine the effects of a
      community-based train-the-trainer intervention on FCCHs policies and practices
      related to healthy eating and physical activity. DESIGN: Quasi-experimental
      design with replication in three independent cohorts of FCCHs.
      SETTING/PARTICIPANTS: Registered FCCHs from 15 counties across Kansas
      participated in the Healthy Kansas Kids (HKK) program. Resource and referral
      agencies (RRAs) in each county recruited and enrolled between five and 15 child
      care providers in their service delivery area to participate in the program. The
      number of registered FCCHs participating in HKK in Years 1 (2006-2007); 2 (2007
      2008); and 3 (2008-2009) of the program were 85, 64, and 87, respectively. A
      stratified random sample of registered FCCHs operating in Kansas (n=297) served
      as a normative comparison group. INTERVENTIONS: Child care trainers from each RRA
      completed a series of train-the-trainer workshops related to promotion of healthy
      eating and physical activity. FCCHs were subsequently guided through a four-step
      iterative process consisting of (1) self-evaluation; (2) goal setting; (3)
      developing an action plan; and (4) evaluating progress toward meeting goals.
      FCCHs also received U.S. Department of Agriculture resources related to healthy
      eating and physical activity. MAIN OUTCOME MEASURES: Nutrition and Physical
      Activity Self-Assessment for Child Care (NAP SACC) self-assessment instrument
      (NAP SACC-SA). Analyses of outcome measures were conducted between 2008 and 2010.
      RESULTS: Healthy Kansas Kids FCCHs exhibited significant improvements in healthy
      eating (Delta=6.9%-7.1%) and physical activity (Delta=15.4%-19.2%) scores
      (p<0.05). Within each cohort, pre-intervention scores were not significantly
      different from the state average, whereas post-intervention scores were
      significantly higher than the state average. CONCLUSIONS: Community-based train
      the-trainer interventions to promote healthy eating and physical activity in
      FCCHs are feasible, sustainable, and effective.

PMID- 21961468
TI  - Geographic disparities in state and district policies targeting youth obesity.
AB  - BACKGROUND: States and school districts nationwide have enacted policies
      targeting youth obesity, but many policies lack specific requirements or
      enforcement language. Geographic disparities in youth obesity could worsen if
      policies are weaker in areas with higher obesity prevalence. PURPOSE: To
      determine if state or district policy strength varies with youth obesity
      prevalence across Census divisions. METHODS: Policies in five domains related to
      nutrition and physical activity in schools were obtained from all states and
      nationally representative samples of 578 and 592 public school districts in the
      2006-2007 and 2008-2009 school years, respectively. Policy language strength was
      rated on a 0-100 scale on both the state and district level. Regression models
      were used to determine if mean 2006-2007 strength scores, and changes in mean
      scores from 2006-2007 to 2008-2009, were associated with youth obesity prevalence
      across Census divisions. Analyses were conducted in 2010. RESULTS: State and
      district policies governing foods sold outside of school meal programs
      ("competitive foods") were stronger in 2006-2007 in the two divisions with the
      highest youth obesity prevalence (East South Central, West South Central).
      Furthermore, mean competitive food policy strength increased the most from 2006
      2007 to 2008-2009 in these divisions. The West South Central had the weakest
      district physical education policies in 2006-2007, however, and was the only
      division in which average strength of district school meal policies decreased.
      CONCLUSIONS: State and districts in Census divisions with the highest youth
      obesity prevalence are taking steps to restrict competitive foods in schools, but
      many have not targeted other policy domains as aggressively.

PMID- 21961467
TI  - Neighborhood and parental supports for physical activity in minority adolescents.
AB  - BACKGROUND: Few studies have examined environmental, home, and parental supports
      for physical activity in underserved adolescents (low income, ethnic minority).
      Given the increasing incidence of obesity in minority adolescents, it is
      important to better understand ecologic determinants of physical activity in
      these youth. This study used an ecologic model to evaluate the significance of
      neighborhood, home, and parental supports for physical activity on moderate-to
      vigorous (MV) physical activity in underserved adolescents. DESIGN: The study was
      a secondary data analysis of a randomized controlled school-based trial "Active
      by Choice Today" (ACT) for increasing physical activity in underserved sixth
      graders. Schools were matched on school size, percentage minorities, percentage
      entitled to free or reduced-price lunch, and urban or rural setting prior to
      randomization. This study used a randomly selected sample of parents (n=280) from
      the intervention and control schools whose adolescent was enrolled in the larger
      trial. SETTING/PARTICIPANTS: A total of 679 6th-grade students (mean age=11.4
      years, 70% African-American, 76% free or reduced-price lunch, 52% female)
      participated in the larger trial. Parents of 280 youth were contacted to
      participate in a telephone survey and 198 (71%) took part in the study.
      INTERVENTIONS: The ACT trial was designed to test the efficacy of a 17-week (1
      academic year) motivational plus behavioral skills intervention versus comparison
      after-school programs on increasing physical activity. A telephone survey was
      developed and was administered within 6 months after the trial began on parents
      of 198 adolescents from the ACT randomized school-based trial during 2005-2007.
      MAIN OUTCOME MEASURES: The primary outcome measure was adolescent MVPA based on 7
      day accelerometry estimates from baseline to mid-intervention. The data were
      analyzed in 2010-2011 and included both parent and adolescent self-reports of
      environmental, home, and family supports for physical activity. RESULTS:
      Regression analyses indicated a significant effect of parental and neighborhood
      supports for physical activity on adolescent MVPA. Adolescents who perceived
      higher (vs lower) levels of parental support for physical activity engaged in
      more minutes of MVPA (B=3.01, SE=1.38, p<0.05) at mid-intervention. Adolescents
      who lived in neighborhoods with more (vs fewer) supports for physical activity
      (parks, lighting), also engaged in more minutes MVPA (B=4.27, SE=2.15, p<0.05).
      CONCLUSIONS: Support from parents and neighborhood quality are both associated
      with increased physical activity in underserved adolescents.

PMID- 21961469
TI  - Liability concerns and shared use of school recreational facilities in
      underserved communities.
AB  - BACKGROUND: In underserved communities, schools can provide the physical
      structure and facilities for informal and formal recreation as well as after
      school, weekend, and summer programming. The importance of community access to
      schools is acknowledged by authoritative groups; however, fear of liability is
      believed to be a key barrier to community access. PURPOSE: The purpose of this
      study was to investigate perceptions of liability risk and associated issues
      among school administrators in underserved communities. METHODS: A national
      survey of school administrators in underserved communities (n=360, response rate
      of 21%) was conducted in 2009 and analyzed in 2010. Liability perceptions in the
      context of community access were assessed through descriptive statistics.
      RESULTS: The majority of respondents (82.2%) indicated concern for liability
      should someone be injured on school property after hours while participating in a
      recreational activity. Among those that did not allow community access, 91% were
      somewhat to very concerned about liability and 86% believed that stronger
      legislation was needed to better protect schools from liability for after-hours
      recreational use. Among those who claimed familiarity with a state law that
      offered them limited liability protection, nearly three fourths were nevertheless
      concerned about liability. CONCLUSIONS: Liability concerns are prevalent among
      this group of school administrators, particularly if they had been involved in
      prior litigation, and even if they indicated they were aware of laws that provide
      liability protection where use occurs after hours. Reducing these concerns will
      be important if schools are to become locations for recreational programs that
      promote physical activity outside of regular school hours.

PMID- 21961470
TI  - Telephone counseling and attendance in a national mammography-screening program a
      randomized controlled trial.
AB  - BACKGROUND: In Germany, a mammography-screening program (MSP) was implemented on
      a national level. It complies with all criteria of the European guidelines for
      quality assurance in screening mammography; however, the attendance rate is 54%,
      falling short of the target attendance rate of 70%. The aim of this study was to
      investigate whether additional telephone counseling improves attendance among
      nonresponders and the level of satisfaction with telephone counseling. DESIGN: In
      a prospective RCT, women identified as nonresponders in the MSP were randomized
      to a control group that received written reminders or to an intervention group
      that additionally received telephone counseling. In a follow-up, a subset of the
      intervention group was contacted by telephone regarding their satisfaction with
      telephone counseling. SETTING/PARTICIPANTS: In 2008, a total of 5477 women aged
      50-69 years who were eligible for the German MSP but had not participated up to 6
      weeks after the first invitation were included in the study. INTERVENTIONS:
      Individual telephone counseling consisted of scripted calls from a trained
      counselor who provided information on MSP and answered the woman's questions.
      MAIN OUTCOME MEASURES: Report of mammography use provided by the screening unit 3
      months after the reminder was sent. RESULTS: Analysis was conducted in 2009.
      Comparison of screening attendance revealed a significantly higher attendance
      rate in the intervention group compared with controls (29.7% vs 26.1%, p=0.0035).
      When only women for whom telephone numbers were available were analyzed,
      attendance was even better (35.5% vs 29.7%, p=0.0004). In the follow-up, 278 of
      404 women were actually surveyed. Of those, 33% stated that telephone counseling
      had influenced their decision, 56% stated that they had undergone screening
      mammography, and 77% agreed that personal telephone counseling should be used
      routinely to encourage nonresponders to go for screening. CONCLUSIONS: Individual
      telephone counseling for nonresponders to a national program for breast cancer
      screening was well accepted by participants and effective. TRIAL REGISTRATION:
      This study is registered at the Australian New Zealand Clinical Trials Registry
      ACTRN12611000645954.

PMID- 21961471
TI  - Racial/Ethnic and poverty disparities in human papillomavirus vaccination
      completion.
AB  - BACKGROUND: Two vaccines against human papillomavirus (HPV), a necessary cause of
      cervical cancer, are currently licensed and recommended for routine
      administration in the U.S. to girls in a three-dose series. PURPOSE: This study
      examined effects of race/ethnicity, poverty, and year on completion of the three
      dose HPV vaccine series among those who initiated vaccination. METHODS: Data from
      the 2008-2009 National Immunization Survey-Teen for girls aged 13-17 years who
      received at least one dose of HPV vaccine (n=7606) were analyzed in 2010-2011
      using logistic regression to adjust for covariates including measures of access
      to care. RESULTS: During this 2-year period, 55% of adolescent girls who
      initiated vaccination completed the three-dose series. Completion was
      significantly higher in 2009 (60%) compared to 2008 (48%; p<0.001). After
      controlling for covariates, adolescents who were black (AOR=0.48, 95% CI=0.40,
      0.57) or Hispanic (AOR=0.75, 95% CI=0.64, 0.88) were significantly less likely to
      complete vaccination than whites. Adolescents living below the federal poverty
      level were significantly less likely to complete vaccination than adolescents
      with household incomes >$75,000 (AOR=0.76, 95% CI=0.63, 0.92). There was no
      significant interaction between race/ethnicity and year (p=0.92). Although
      poverty was associated with lower completion rates in 2008, this association was
      not observed in 2009 (p<0.05 for poverty-year interaction). CONCLUSIONS: HPV
      vaccination completion rates increased between 2008 and 2009. However,
      significant differences by race/ethnicity and poverty were observed, and the
      racial/ethnic differences persisted.

PMID- 21961472
TI  - The impact of menu labeling on fast-food purchases for children and parents.
AB  - BACKGROUND: Nutrition labeling of menus has been promoted as a means for helping
      consumers make healthier food choices at restaurants. As part of national health
      reform, chain restaurants will be required to post nutrition information at point
      of-purchase, but more evidence regarding the impact of these regulations,
      particularly in children, is needed. PURPOSE: To determine whether nutrition
      labeling on restaurant menus results in a lower number of calories purchased by
      children and their parents. METHODS: A prospective cohort study compared
      restaurant receipts of those aged 6-11 years and their parents before and after a
      menu-labeling regulation in Seattle/King County (S/KC) (n=75), with those from a
      comparison sample in nonregulated San Diego County (SDC) (n=58). Data were
      collected in 2008 and 2009 and analyzed in 2010. RESULTS: In S/KC, there was a
      significant increase from pre- to post-regulation (44% vs 87%) in parents seeing
      nutrition information, with no change in SDC (40% vs 34%). Average calories
      purchased for children did not change in either county (823 vs 822 in S/KC, 984
      vs 949 in SDC). There was an approximately 100-calorie decrease for the parents
      postregulation in both counties (823 vs 720 in S/KC, 895 vs 789 in SDC), but no
      difference between counties. CONCLUSIONS: A restaurant menu-labeling regulation
      increased parents' nutrition information awareness but did not decrease calories
      purchased for either children or parents.

PMID- 21961473
TI  - Dynamic urban food environments a temporal analysis of access to healthy foods.
AB  - BACKGROUND: Low-income, urban populations' limited access to healthy foods is
      often pointed to as a key barrier to improving nutrition. Although much has been
      written on identifying urban "food deserts," little has been done to examine how
      the food environment changes over the course of 1 year. PURPOSE: This study was
      designed to dynamically describe the urban food environment as a means to
      identify when at-risk neighborhoods are without access to healthy food. METHODS:
      Demographic and road data of Buffalo NY from the 2000 U.S. Census, a 2010 listing
      of city supermarkets, and 2011 government records of the time and location of
      urban farmers' markets are mapped. Road network distances from block groups to
      supermarkets and farmers' markets are calculated. A computer simulation, written
      in 2011, examines the market closest to each block group for 52 weeks. RESULTS:
      The average distance to markets with produce from block groups with poverty
      levels in the top 10th percentile is greater than that across all block groups
      during winter and spring months. However, during the farmers' market season, the
      same impoverished block groups are on average closer to markets when compared to
      all block groups. CONCLUSIONS: Including the temporal dimension in an analysis of
      healthy food access generates a more complex picture of urban food-desert
      locations. The implications are that spatiotemporal factors should be used to
      inform appropriate interventions for creating an equitable food environment.

PMID- 21961474
TI  - Neighborhood environment and physical activity among youth a review.
AB  - CONTEXT: Research examining the association between environmental attributes and
      physical activity among youth is growing. An updated review of literature is
      needed to summarize the current evidence base, and to inform policies and
      environmental interventions to promote active lifestyles among young people.
      EVIDENCE ACQUISITION: A literature search was conducted using the Active Living
      Research (ALR) literature database, an online database that codes study
      characteristics and results of published papers on built/social environment and
      physical activity/obesity/sedentary behavior. Papers in the ALR database were
      identified through PubMed, Web of Science, and SPORTDiscus using systematically
      developed and expert-validated search protocols. For the current review,
      additional inclusion criteria were used to select observational, quantitative
      studies among youth aged 3-18 years. EVIDENCE SYNTHESIS: Papers were categorized
      by design features, sample characteristics, and measurement mode. Relevant
      results were summarized, stratified by age (children or adolescents) and mode of
      measurement (objective or perceived) for environmental attributes and physical
      activity. Percentage of significant results was calculated. CONCLUSIONS: Mode of
      measurement greatly influenced the consistency of associations between
      environmental attributes and youth physical activity. For both children and
      adolescents, the most consistent associations involved objectively measured
      environmental attributes and reported physical activity. The most supported
      correlates for children were walkability, traffic speed/volume, access/proximity
      to recreation facilities, land-use mix, and residential density. The most
      supported correlates for adolescents were land-use mix and residential density.
      These findings support several recommendations for policy and environmental
      change from such groups as the IOM and National Physical Activity Plan.

PMID- 21961475
TI  - Body mass index and the built and social environments in children and adolescents
      using electronic health records.
AB  - BACKGROUND: No prior studies in children have evaluated how age may modify
      relationships of the built and social environments with BMI, nor evaluated the
      range of scales and contexts over which places may influence health. PURPOSE: To
      systematically evaluate associations of 33 environmental measures in three
      domains (land use, physical activity, and social environments) with BMI in
      children and adolescents in five geographies. METHODS: A cross-sectional,
      multilevel analysis was completed in 2009-2010 of electronic health record data
      (2001-2008) from 47,769 children aged 5-18 years residing in a 31-county region
      of Pennsylvania. Associations of environmental measures with BMI were evaluated
      using 0.5-mile network buffers; census tracts; minor civil divisions (i.e.,
      townships, boroughs, cities); a mixed definition of place (townships, boroughs,
      and census tracts in cities); and counties, overall and by age strata. RESULTS:
      Among all children, lower levels of community socioeconomic deprivation and
      greater diversity of physical activity establishments were associated with lower
      BMI. Associations of environmental measures differed by age, depending on scale
      and context. For example, higher population density was associated with lower BMI
      in older children; this effect was strongest in the larger geographies.
      Similarly, a lower level of county sprawl was associated with lower BMI in older
      children. CONCLUSIONS: Associations differed by age and definition of place,
      suggesting that the benefits of environmental intervention may not be uniform
      across the childhood age range. The study demonstrated the utility of using
      electronic patient information for large-scale, population-based epidemiologic
      research, a research area of growing interest and investment in the U.S.

PMID- 21961476
TI  - Searching for an indicator of the influence of the tobacco lobby on politicians.

PMID- 21961477
TI  - Gender-dependence of substituted judgment on quality of life in patients with
      dementia.
AB  - BACKGROUND: Substituted judgment asks the proxy to decide what the patient would
      have decided, had he or she been competent. It is unclear whether substituted
      judgment of the patient's quality of life can serve as a surrogate measure in
      patients with dementia. METHODS: 212 patients with dementia and their proxies
      were interviewed in their homes. Dementia syndrome was characterized with
      cognitive, non-cognitive and functional scales. Quality of life (QoL) was
      assessed with the QoL-AD. RESULTS: Substituted judgment of the patient's QoL was
      unrelated to dementia severity but also correlated with the proxie's own QoL (r =
      0.356; p < 0.001). Gender-specific analysis reveals that for male proxies the
      most important variable is severity of patient's depression (r = -0.895; p =
      0.001) while for female proxies it is the proxie's own QoL (r = 0.371; p <
      0.001). Subjective burden correlates with the proxie's QoL in females (r = 
      0.282; p = 0.001) but not in males (r = -0.163, p = 0.161). CONCLUSION:
      Substituted judgment of the patient's QoL does not correlate with dementia
      severity. Substituted judgment is subject to proxy-related variables in a gender
      dependent fashion and therefore not suited to serve as an appropriate surrogate
      of the patients' quality of life.

PMID- 21961478
TI  - MicroRNA profile of polyunsaturated fatty acid treated glioma cells reveal
      apoptosis-specific expression changes.
AB  - BACKGROUND: Polyunsaturated fatty acids (PUFAs) such as gamma-linolenic acid
      (GLA), arachidonic acid (AA) and docosahexaenoic acid (DHA) have cytotoxic action
      on glioma cells. RESULTS: We evaluated the cytotoxic action of GLA, AA and DHA on
      glioma cells with specific reference to the expression of miRNAs. Relative
      expression of miRNAs were assessed by using high throughput nanocapillary real
      time PCR. Most of the miRNA target genes that showed altered expression could be
      classified as apoptotic genes and were up-regulated by PUFA or temozolomide
      treatment, while similar treatments resulted in repression of the corresponding
      mRNAs, such as cox2, irs1, irs2, ccnd1, itgb3, bcl2, sirt1, tp53inp1 and k-ras.
      CONCLUSIONS: Our results highlight involvement of miRNAs in the induction of
      apoptosis in glioma cells by fatty acids and temozolomide.

PMID- 21961479
TI  - Conformation-changing aggregation in hydroxyacetone: a combined low-temperature
      FTIR, jet, and crystallographic study.
AB  - Aggregation in hydroxyacetone (HA) is studied using low-temperature FTIR,
      supersonic jet expansion, and X-ray crystallographic (in situ
      cryocrystallization) techniques. Along with quantum chemical methods (MP2 and
      DFT), the experiments unravel the conformational preferences of HA upon
      aggregation to dimers and oligomers. The O-H...O?C intramolecular hydrogen bond
      present in the gas-phase monomer partially opens upon aggregation in supersonic
      expansions, giving rise to intermolecular cooperatively enhanced O-H...O-H
      hydrogen bonds in competition with isolated O-H...O?C hydrogen bonds. On the
      other hand, low-temperature IR studies on the neat solid and X-ray
      crystallographic data reveal that HA undergoes profound conformational changes
      upon crystallization, with the HOCC dihedral angle changing from ~0 degrees  in
      the gas phase to ~180 degrees  in the crystalline phase, hence giving rise to a
      completely new conformation. These conclusions are supported by theoretical
      calculations performed on the geometry derived from the crystalline phase.

PMID- 21961480
TI  - Alcohol-related cognitive impairment in New South Wales hospital patients aged 50
      years and over.
AB  - OBJECTIVES: The aim of this study was to describe the principal reasons for
      admission, medical comorbidities, interventions and outcomes of patients admitted
      to New South Wales hospitals with alcohol-related cognitive impairment. METHODS:
      We extracted data from the NSW Admitted Patient Care Database for nearly 410 000
      multi-day hospital admissions from 222 public hospitals ending between July 2006
      and June 2007 for people aged 50 and over. Data linkage using a unique patient
      identifier, derived by the Centre for Health Record Linkage identified hospital
      transfers and readmissions for individual patients. Using ICD10-AM codes, we
      identified patients with alcohol-related dementia, amnesic syndrome due to
      alcohol, and Wernicke's encephalopathy, their principal reasons for admission and
      medical comorbidities, and procedures undertaken. Outcomes were length of stay,
      mortality, discharge destination, and readmission. RESULTS: A total of 462
      patients diagnosed with alcohol-related dementia (n = 300; 82% male, mean age
      63.9 years), Wernicke's encephalopathy (n = 77) or amnesic syndrome due to
      alcohol (n = 126) were identified with overlap between diagnoses. Alcohol-related
      dementia occurred in 1.4% of dementia patients, and was more likely to occur in
      younger age groups and men than other types of dementia. Alcohol-related mental
      disorder was recorded in 70% of alcohol-related dementia multi-day admissions:
      dependence (52%), 'harmful use' (11%) and withdrawal (12%). Principal reasons for
      admission for multi-day stays included alcohol-related mental disorder (18%),
      liver disease (11%) and injuries/poisonings (10%). Medical comorbidity was
      common. Like other dementia patients, alcohol-related dementia patients had
      longer length of stay (mean of 15 days) than non-dementia patients and more
      transfers to residential care (7%). However, mortality was similar to non
      dementia patients (5%). Discharge at own risk was high (3.7%). CONCLUSIONS:
      Alcohol-related dementia is a preventable and potentially reversible condition.
      Investigation of intervention strategies initiated during hospitalization are
      warranted.

PMID- 21961481
TI  - Reformulation of current recommendations for target serum lithium concentration
      according to clinical indication, age and physical comorbidity.
AB  - BACKGROUND: There have been significant changes in the nature of psychiatric
      patient populations and patterns of drug prescribing in mood disorders since
      serum lithium monitoring was introduced. It seems opportune to review current
      guidelines for target lithium concentration given the decline in lithium
      monotherapy and increase in the numbers of older people and those with comorbid
      physical disease administered lithium. METHOD: A review was made of the
      literature of lithium monitoring and target serum concentration in mood
      disorders, older people, and comorbid physical illness. RESULTS: Current
      guidelines, which generally recommend a target serum concentration of 0.5/0.6 to
      1.1/1.2 mmol/L, have a number of limitations. A target lithium level of > 0.8
      mmol/L is inappropriate given poor tolerability, and adequate efficacy when
      combination lithium-antipsychotic therapy is used at this or lower levels.
      Guidelines have largely failed to match specific clinical indications to serum
      levels, and to consider comorbid physical illness factors known to be associated
      with lithium toxicity. CONCLUSION: For most patients, a target serum lithium
      concentration range of 0.5-0.8 mmol/L, varying according to clinical indication,
      age and concurrent physical status, seems most appropriate in enhancing efficacy
      and minimizing adverse effects. The lower end of this range (0.5-0.6 mmol/L) is
      recommended for patients 50 years and over; those with diabetes insipidus, renal
      impairment or thyroid dysfunction; those administered diuretics, angiotensin
      converting enzyme (ACE) inhibitors or non-steroidal anti-inflammatory drugs
      (NSAIDs)/COX-2 inhibitors; and in the prophylaxis of bipolar depression and
      management of acute unipolar depression. The higher end of this range (0.7-0.8
      mmol/L) is recommended in the management of acute mania and prophylaxis of mania.

PMID- 21961482
TI  - Adverse drug reactions (ADRs) associated with hospital admissions - elderly
      female patients are at highest risk.
AB  - BACKGROUND: ADRs represent a significant problem in drug utilisation. The
      prevalence of admissions caused by ADRs varies depending on the observational
      site, studied population, data collection method and the used definitions. Women
      seem to be more frequently affected than men. OBJECTIVE: To assess the incidence
      and quality of ADRs related to hospital admissions, to identify the drugs most
      commonly involved and to define risk factors and preventive strategies for those
      ADRs. MATERIAL AND METHODS: 3,190 medical records of all newly admitted internal
      ward patients were assessed in a prospective observational study in an internal
      hospital over 6 months. Potential ADRs at hospital admission were identified
      following a list of suspicious symptoms and laboratory results. Cases were
      evaluated by means of a computer tool and data-base specialized on detecting
      causality and severity of ADRs. RESULTS: 304 ADRs were identified in 242 patients
      (7.6%), with 60% directly leading to admission. More women than men encountered
      an ADR (10 vs. 6%, p < 0.005). Analyzed separately by age groups, this gender
      difference became significant at an age of >= 81 years. The most common ADRs were
      electrolyte imbalances and over-anticoagulation. Diuretics and vitamin K
      antagonists were significantly correlated with ADRs. 62% of all ADRs were severe
      or life-threatening. CONCLUSION: ADRs leading or related to hospital admission
      are highly prevalent. Older age and female gender are significantly associated
      with ADR related hospital admissions. Causative drugs are the ones prescribed
      most frequently. Multidisciplinary preventive strategies and surveillance methods
      are necessary to ensure better care and patient safety especially for elderly
      women.

PMID- 21961483
TI  - Imaging patterns and prognosis of patients with gefitinib-related interstitial
      lung disease.
AB  - PURPOSE: We aimed to summarize the imaging findings of 25 patients with gefitinib
      related interstitial lung disease (ILD), and identify the factors related to
      prognosis of gefitinib-related ILD in patients with non-small-cell-lung cancer.
      MATERIALS AND METHODS: Diagnosis of gefitinib-induced ILD by at least two chest
      radiologists was based on a review and analysis of the chest radiography and CT
      findings plus clinical data in the medical records. All patients were diagnosed
      with Stage III - IV non-small-cell carcinoma (adenocarcinoma (n = 24),
      bronchioalveolar cell carcinoma (n = 1)) and essential clinical data such as
      gefitinib as first-line use and survival status were recorded and analyzed to
      determine whether these were prognosis predictors. The imaging findings were
      classified into four patterns according to the previous largest study in Japan.
      RESULTS: The 25 chest radiographs were classified as Pattern A (n = 8), Pattern B
      (n = 3), Pattern C (n = 6), and pattern D (n = 8). Likewise the 23 CT images were
      classified as pattern A (n = 8; 34.8%), B (n = 3; 13%), C (n = 5; 21.7%), and D
      (n = 7; 30.4%). The mortality rate was significantly higher in patients with
      pattern D than in patients with the other patterns. Pattern D imaging findings
      were also significantly correlated with non first-line use of gefitinib (p =
      0.007). CONCLUSIONS: We found an increase in mortality rate in patients with
      gefitinib associated ILD/pattern D compared to other radiological patterns.
      Familiarity with these imaging patterns can facilitate early and accurate
      diagnosis and help physicians gauge clinical prognosis of gefitinib-related ILD.

PMID- 21961484
TI  - A thorough QT study to evaluate the effects of singledose exenatide 10 MUg on
      cardiac repolarization in healthy subjects.
AB  - OBJECTIVE: This was a singledose, randomized, positive- and placebo-controlled,
      double-dummy, double-blinded, 3-period crossover thorough QT study of exenatide,
      a glucagon-like peptide-1 receptor agonist for the treatment of Type 2 diabetes
      that enhances insulin secretion in a glucose- dependent fashion. METHODS: Healthy
      subjects (n = 70) underwent an initial tolerability screening, receiving
      subcutaneous exenatide 10 MUg daily for 3 consecutive days. Subjects who passed
      tolerability screening (n = 62) received exenatide 10 MUg, placebo, and
      moxifloxacin (400 mg orally; positive control) separated by washout periods of
      approximately 5 days. Twelve-lead electrocardiograms and blood samples for plasma
      exenatide, glucose, and insulin were collected. QT intervals were heart rate
      corrected using Fridericia's correction (QTcF) and an individual correction
      (QTcI) and were analyzed as change from predose (DeltaQTcF, or DeltaQTcI). The
      relationships between the QTc interval and plasma exenatide, glucose, and insulin
      concentrations were also explored. RESULTS: Based on DeltaQTcF and DeltaQTcI
      assessments, exenatide 10 MUg did not show a clinically significant prolongation
      of QT compared with placebo; the upper bound of the 2-sided 90% confidence
      interval (CI) for the largest mean difference from placebo was < 10 msec with
      both corrections. A positive slope was observed between plasma exenatide and
      DeltaDeltaQTcF (0.02 (95% CI 0.01, 0.03), p < 0.001); no significant slope was
      observed between plasma exenatide concentrations and DeltaDeltaQTcI (0.01 (95% CI
      0.00, 0.02), p = 0.064). The plasma exenatide versus QTc analyses may be
      confounded by exenatide's glucose-lowering effect. A negative slope was observed
      between plasma glucose and [delta]QTcF (-1.5 (95% CI -2.2, -0.7), p < 0.001) and
      between plasma glucose and DeltaQTcI (-1.6 (95% CI -2.3, -0.9), p < 0.0001).
      Plasma insulin and DeltaQTcF were not correlated. CONCLUSION: This study
      demonstrated that single-dose exenatide 10 MUg was not associated with clinically
      meaningful prolongation of the QTc interval.

PMID- 21961485
TI  - Antiplatelet therapy in diabetic ischemic stroke patients: associated factors and
      outcomes.
AB  - BACKGROUND: Patients with diabetes mellitus (DM) are more prone to develop
      atherosclerotic complications including stroke. Moreover, as a primary and
      secondary prevention of stroke, antiplatelet therapy is recommended by clinical
      guidelines for patients with DM. AIMS: This study aimed to determine the
      prevalence of antiplatelet therapy use prior to current stroke in diabetic
      ischemic stroke patients, to examine the factors associated with the use of this
      important therapy and to assess the impact of the previous use of antiplatelet
      therapy on ischemic stroke outcomes. METHODS: An observational study of diabetic
      acute ischemic stroke patients attending a Malaysian hospital during a 1-year
      period was carried out. Demographic information, risk factors, previous
      antiplatelet use and variables used to assess stroke outcomes were collected from
      medical records. RESULTS: Overall, 295 diabetic stroke patients were analyzed.
      The prevalence of previous antiplatelet use among diabetic patients was 38.3%.
      The independent variables associated with the previous use of antiplatelet
      medication were previous stroke attack (p < 0.001) and ischemic heart disease (p
      < 0.001). Better outcomes as measured by a minor Glasgow Coma Scale at admission
      (p = 0.032), and a higher Modified Barthel index at discharge (p = 0.027) were
      observed among patients on previous antiplatelet therapy. CONCLUSION: Our data
      suggest that antiplatelet therapy is under prescribed among such diabetic stroke
      patients, particularly in primary prevention. Effective methods to increase
      antiplatelet use and to enhance the adherence of clinical practice guidelines
      should be considered at the national and community level.

PMID- 21961486
TI  - The efficacy of nebulized procaterol versus nebulized salbutamol for the
      treatment of moderate acute asthma: a randomized, double-blind, parallel group
      study.
AB  - OBJECTIVE: beta2 agonists have been used widely as relievers in asthma
      management. Procaterol is a selective beta2 agonist, claimed to be more selective
      than salbutamol. The present study aimed to compare the efficacy of nebulized
      procaterol with nebulized salbutamol in the treatment of moderate acute asthma.
      METHODS: This was a randomized, double-blind, parallel group study in 140
      patients with moderate acute asthma according to modified GINA 1998 who visited
      emergency department of Persahabatan Hospital, Jakarta. Patients were randomly
      assigned to receive three doses of either nebulized procaterol or salbutamol. The
      primary efficacy variable was the improvement in predicted peak expiratory flow
      rate (PEFR), while the secondary efficacy variable was the improvement in asthma
      score and the incidence and severity of adverse events. This study is registered
      at Current Controlled Trials, number ISCTRN25669625. RESULTS: Baseline
      characteristics were similar in both groups. After treatment, there were
      significant improvement of % PEFR (p < 0.001) and asthma score (p < 0.001) in
      procaterol (n = 68) and salbutamol (n = 69) groups. It was shown that procaterol
      and salbutamol produced similar efficacy in improving % predicted PEFR and
      decreasing asthma score. Both treatments were well tolerated. Palpitation and
      sinus tachycardia were found as adverse events with low incidence. CONCLUSION: In
      moderate acute asthma, nebulized procaterol and nebulized salbutamol were both
      effective in improving PEFR and decreasing asthma score. Both treatments were
      well tolerated, adverse reactions were rare.

PMID- 21961487
TI  - Glucocorticoid-resistant Evans' syndrome successfully controlled with low-dose
      cyclosporine.
AB  - OBJECTIVE: To present a patient suffering from Evans' syndrome (ES), whose bouts
      of severe cytopenia were prevented by low-dose cyclosporine maintenance therapy.
      CASE SUMMARY: A boy suffering from frequent mild respiratory infections, first
      time evaluated in a tertiary care pediatric center at age 4, was found to have
      lymphadenopathy and mild splenomegaly. The thrombocytopenia was first noted at
      age 6. He was diagnosed to have ES at the age of 8, during another bout of
      thrombocytopenia, this time associated with Coombs-positive hemolytic anemia.
      Immunoglobulin concentration in the plasma was measured repeatedly, and was in
      the normal range, or even increased. Lymphocyte subpopulation numbers were in the
      normal range, with decreased CD4+/ CD8+ ratio (0.6). Autoimmune
      lymphoproliferative syndrome was excluded by the absence of CD4-CD8- T
      lymphocytes. Since the patient failed to respond to standard therapy with
      prednisolon 2 mg/kg, high dose intravenous methylprednisolone (10 mg/ kg/d for 3
      days) and high dose intravenous immunoglobulin (1 g/kg/d for 2 days),
      cyclosporine treatment was initiated (6 mg/ kg/d) and resulted in normalization
      of platelet count and resolution of hemolysis. Two attempts to withdraw
      cyclosporine therapy resulted in life-threatening hemolytic crisis with severe
      thrombocytopenia, requiring the re-institution of cyclosporine. The dose of
      cyclosporine was eventually tapered to the present 0.5 mg/kg, corresponding to
      drug serum levels of 5 - 8 mg/ml. The patient is now free of manifestations of
      Evans' syndrome but, after 20 years of cyclosporine treatment, has slightly
      impaired kidney function. CONCLUSION: Low-dose cyclosporine therapy given to our
      patient appears to have subdued the autoimmune process thought to underlie the
      manifestations of ES, albeit at the cost of some toxicity to the kidneys.

PMID- 21961488
TI  - Lepirudin dose-dependently increases thrombelastography parameters at therapeutic
      plasma concentrations as measured with ROTEM(r) - a pilot study.
AB  - BACKGROUND: The aim of this in-vitro pilot study was to assess the usefulness of
      the thrombelastograph ROTEM(r) for determining the anticoagulant activity of
      lepirudin. METHODS: The ROTEM(r) parameters, clotting-time, clot formation time
      and maximum clot firmness were measured in the presence of increasing
      concentrations of lepirudin (10-4 MUg/ml - 10 MUg/ml). Citrated blood was
      obtained from 16 healthy male subjects. RESULTS: Clotting-time increased from
      79.1 +/- 53.4 s at baseline to 194.1 +/- 151.9 s at a drug concentration of
      1MUg/ml as measured with EXTEM (p < 0.0001). Borderline significance was found
      for the difference between maximum clot firmness at baseline (60.2 +/- 4.3 mm)
      and after drug application (55.5 +/- 6.5 mm). CONCLUSIONS: This pilot
      investigation shows that the ROTEM(r) device may be suitable for monitoring
      lepirudin at low concentrations but the results should be confirmed in a larger
      study and the ROTEM(r) device validated against standard methods.

PMID- 21961489
TI  - Bioequivalence assessment of metformin hydrochloride using a limited sampling
      strategy.
AB  - OBJECTIVE: The aim of this study was to develop a limited sampling strategy (LSS)
      that can be used to assess the bioequivalence of two metformin hydrochloride
      preparations. METHODS: Healthy subjects (n = 20) enrolled in the bioequivalence
      study received a single oral tablet of 1,000 mg metformin reference formulation
      or test formulation. The plasma concentration of metformin was determined using a
      validated HPLC method. A multiple linear regression analysis of the observed
      metformin Cmax and AUC0-24 versus the concentration of reference formulation was
      performed to develop LSS models for estimating these parameters. The models were
      internally validated by the Jackknife method. The best models were employed to
      assess the bioequivalence of the two metformin formulations. RESULTS: The linear
      relationship between pharmacokinetic parameters and a single concentration point
      was poor. Several models for the estimation of these parameters met the
      predefined criteria (r2 > 0.9). The Jackknife validation procedure revealed that
      LSS models based on two sampling times - C1.5 and C2 for Cmax; C4.0 and C10.0 for
      AUC0-24 - were accurate predictor of Cmax and AUC0-24. Prediction errors (PE)
      were less than 2%, and absolute prediction errors (AE) were less than 10%. PEs
      beyond 15% occurred in less than 5% of total samples. The bioequivalence
      assessment of the two metformin formulations, based on the best LSS models,
      provided results similar to those obtained using all the observed concentration
      time data points, and indicated that the two metformin formulations were
      bioequivalent. CONCLUSION: A LSS method for assessing the bioequivalence of
      metformin formulations was established and proved to be applicable and accurate.
      This LSS method could be considered appropriate for a metformin bioequivalence
      study, providing an inexpensive cost of sampling acquisition and analysis.

PMID- 21961496
TI  - VB-111 for cancer.
AB  - INTRODUCTION: Antibody, small molecule and protein inhibitors of angiogenesis are
      used in the management of several cancers. These do not specifically target tumor
      vascularity, and resistance can be problematic. VB-111 is a vascular-targeting
      agent consisting of a non-replicating adenovirus vector with a pre-proendothelin
      1 promoter that encodes an apoptotic receptor. AREAS COVERED: The rationale and
      design of VB-111, its mechanism of action, and preclinical studies examining
      antitumor activity, toxicology and pharmacodynamics are reviewed. Phase I and
      Phase II clinical trials are also reviewed. EXPERT OPINION: VB-111 is a vascular
      targeting gene therapeutic that is both tissue- and condition-specific, with
      effects limited to endothelial cells undergoing angiogenesis. Systemic
      administration produces selective destruction of tumor vascularity. Synergistic
      antitumor activity can be observed when combined with chemotherapy. VB-111 has
      been found to be safe and well tolerated in a Phase I clinical trial in patients
      with advanced solid tumors. Phase II clinical trials are in progress. VB-111 is
      novel agent for cancer that may have application as monotherapy and in
      combination with other therapies.

PMID- 21961497
TI  - Minor changes in effective half-life during fractionated 177Lu-octreotate
      therapy.
AB  - AIMS: Fractionated (177)Lu-DOTA-octreotate therapy has been reported to be an
      effective treatment option for patients with generalized neuroendocrine tumors.
      In our clinic, full individual dosimetry is performed during the first therapy
      cycle, while dosimetry at later cycles is based on the 24 h uptake measurement
      assuming an unchanged effective half-life. Our aim was to evaluate this
      assumption and the variation in the 24 h uptake during therapy. PATIENTS: Thirty
      patients, 13 women and 17 men, were included in the study. METHODS: During the
      first therapy cycle the (177)Lu-concentration was measured with SPECT/CT over the
      abdomen at 24 h, 96 h and 168 h after infusion. The effective half-life was
      determined for the kidneys, liver and spleen. The procedure was repeated at cycle
      4 or 5. RESULTS: The median ratio between the effective half-lives of the latter
      and the first cycle was 0.97 and 1.01 for the right and left kidney, with a range
      of 0.89-1.01 (1st-3rd quartile) and 0.93-1.05, respectively. DISCUSSION: The mean
      value of the ratios was slightly lower than one, indicating a tendency towards
      increased activity elimination during therapy. In individual patients,
      significant changes were found for all organs, often when a large tumor burden
      reduction occurred during treatment. Possible contributing factors appeared to be
      larger amounts of non-tumor bound tracer, improved organ function (kidneys),
      decrease of vessel obstruction (spleen), less scatter from large tumors and
      reduction of small metastases (liver and spleen). CONCLUSION: With most patients
      it is safe to estimate absorbed doses to kidneys, liver and spleen from 24 h
      activity concentration assuming an unchanged effective half-life during therapy.
      Patients with risk factors for kidney dysfunction need to be monitored in more
      detail. Simplified dosimetry based on the assumption of unchanged effective half
      life can function as guidance to the number of therapy cycles an individual
      patient can tolerate.

PMID- 21961498
TI  - FOLFOX regimen in pancreatic acinar cell carcinoma: case report and review of the
      literature.

PMID- 21961499
TI  - Reference values for the EORTC QLQ-C30 quality of life questionnaire in a random
      sample of the Swedish population.
AB  - AIM: To obtain reference values for health-related quality of life (HRQL)
      measured with the European Organization for Research and Treatment of Cancer
      (EORTC) Core Quality of Life Questionnaire (QLQ-C30) in a random sample of the
      adult Swedish population. METHODS: A population-based survey of a random sample
      of 7002 Swedish adults aged 40-79 years, frequency-matched to reflect the age and
      sex distribution of upper gastrointestinal cancer patients. Scales were scored on
      a 0-100 metric according to standard procedures. Functions and symptoms were
      dichotomized into "poor" versus "good" function, and "symptomatic" and "no or
      minor symptoms", respectively. The results were stratified for age and gender.
      RESULTS: The questionnaire was completed by 4910 (70.5%) of 6969 eligible
      participants. Missing values were limited. HRQL was found to vary according to
      age and sex. Generally, men reported better functioning and fewer symptoms than
      women. The most common symptoms were fatigue, pain, and insomnia. CONCLUSION: The
      reference values provided can be used as a surrogate baseline measure in HRQL
      research, and when evaluating the effect of interventions on HRQL in cancer
      patients.

PMID- 21961500
TI  - Relationship of biochemical parameters, BMI and blood pressure with age, gender
      and ethnicity of Trinidadian type 2-diabetic subjects.
AB  - OBJECTIVE: To determine the relationship of biochemical parameters, BMI and blood
      pressure with age, gender and ethnicity of Trinidadian type 2-diabetic subjects.
      METHODS: A retrospective case control study comprised of 1794 patient (740 males
      and 1054 females). RESULTS: The correlation was found for lipid profile with age
      and gender in diabetic subjects. There was a positive significant correlation in
      LDL-C values for all age groups. Serum creatinine concentrations significantly
      varied amongst ethnicity (p = 0.02). Of the known ethnicities, East Indians had
      the highest mean creatinine value (1.00 +/- 0.47 mg/dl). The univariate general
      linear model showed that lipid profile had many associations with gender and
      ethnicity in type 2 diabetic subjects. LDL-C had significant differences between
      gender (p = 0.04) and diabetes (p = 0.01). CONCLUSIONS: Varied lipid profile with
      elevated systolic blood pressure and BMI are associated in type 2 diabetic
      patients with respect to age, gender and ethnicity.

PMID- 21961501
TI  - Editorial issue 6: eating disorders.

PMID- 21961503
TI  - Effect of arginine on the alcohol dehydrogenase and acetaldehyde dehydrogenase
      enzymes of alcohol metabolism in Saccharomyces cerevisiae.
AB  - Arginine possesses advantageous pharmacological properties such as liver injury
      protection. We have previously shown that the arginine stimulated the activities
      of commercial alcohol dehydrogenase (ADH, EC 1.1.1.1) and acetaldehyde
      dehydrogenase (ALDH, EC 1.2.1.10) enzymes in vitro experiment. We therefore
      examined on the activities, zymogram staining intensity, and protein expression
      of alcohol metabolizing ADH and ALDH in Saccharomyces cerevisiae cultured in a
      medium supplemented with different concentrations of arginine. The enhanced
      activity, zymogram staining intensity, and protein expression of ADH in the cell
      free extracts of S. cerevisiae showed at 0.01 and 0.05% (w/v) arginine
      supplementation. These parameters of ALDH in the cell-free extracts of S.
      cerevisiae showed in the 0.005-0.05% arginine treatment concentration, but these
      parameters were shown to be decreased at a concentration of 0.1% (w/v) arginine,
      which was the highest supplementation. These results indicate that arginine can
      be used to enhance the enzyme activities, staining intensity for the protein
      activity in the zymogram analysis, and increased protein expression of ADH and
      ALDH in S. cerevisiae. These results also indicate that arginine can be used to
      the protection of alcoholic liver injury and hangover by strong activation of
      alcohol metabolizing ADH and ALDH.

PMID- 21961502
TI  - World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the
      pharmacological treatment of eating disorders.
AB  - OBJECTIVES: The treatment of eating disorders is a complex process that relies
      not only on the use of psychotropic drugs but should include also nutritional
      counselling, psychotherapy and the treatment of the medical complications, where
      they are present. In this review recommendations for the pharmacological
      treatment of eating disorders (anorexia nervosa (AN), bulimia nervosa (BN), binge
      eating disorder (BED)) are presented, based on the available literature. METHODS:
      The guidelines for the pharmacological treatment of eating disorders are based on
      studies published between 1977 and 2010. A search of the literature included:
      anorexia nervosa bulimia nervosa, eating disorder and binge eating disorder. Many
      compounds have been studied in the therapy of eating disorders (AN:
      antidepressants (TCA, SSRIs), antipsychotics, antihistaminics, prokinetic agents,
      zinc, Lithium, naltrexone, human growth hormone, cannabis, clonidine and tube
      feeding; BN: antidepressants (TCA, SSRIs, RIMA, NRI, other AD), antiepileptics,
      odansetron, d-fenfluramine Lithium, naltrexone, methylphenidate and light
      therapy; BED: antidepressants (TCA, SSRIs, SNRIs, NRI), antiepileptics, baclofen,
      orlistat, d-fenfluramine, naltrexone). RESULTS: In AN 20 randomized controlled
      trials (RCT) could be identified. For zinc supplementation there is a grade B
      evidence for AN. For olanzapine there is a category grade B evidence for weight
      gain. For the other atypical antipsychotics there is grade C evidence. In BN 36
      RCT could be identified. For tricyclic antidepressants a grade A evidence exists
      with a moderate-risk-benefit ratio. For fluoxetine a category grade A evidence
      exists with a good risk-benefit ratio. For topiramate a grade 2 recommendation
      can be made. In BED 26 RCT could be identified. For the SSRI sertraline and the
      antiepileptic topiramate a grade A evidence exists, with different recommendation
      grades. CONCLUSIONS: Additional research is needed for the improvement of the
      treatment of eating disorders. Especially for anorexia nervosa there is a need
      for further pharmacological treatment strategies.

PMID- 21961504
TI  - Removal of gaseous polycyclic aromatic hydrocarbons from cooking fumes using an
      atmospheric plasma reactor.
AB  - Plasma technology is becoming increasingly important for treating various
      environmental pollutants. Treatment of polycyclic aromatic hydrocarbons (PAHs),
      such as those emitted from electric ovens while roasting pork, using an
      atmospheric plasma reactor has seldom been studied. This study investigated the
      characteristics of five PAH species (acenaphthalene (AcPy), acenaphthene (Acp),
      anthracene (Ant), benzo[a]anthracene (BaA), and benzo(ghi)perylene (BghiP)) in
      fumes emitted while roasting pork. The removal efficiency at different plasma
      output powers (0.112, 0.138, and 0.156 kJ/m(3)) of the reactor was also
      investigated. In the experiments, cooking fumes were generated by a small
      electrical oven, with pork being roasted at 200  degrees C. After a steady state
      was reached, samples were collected at the inlet and outlet of the atmospheric
      plasma reactor. The PAHs were analyzed using gas chromatography-mass
      spectrophotometry. The experimental results indicated that the removal efficiency
      for each PAH was highest with the highest plasma reactor output power. This was
      also true of the total PAH concentration, but the total toxic equivalence,
      BaP(eq), was lowest at the medium power output. This demonstrates that the total
      toxicity and the removal of PAHs were not directly proportional, and careful
      consideration must be made by engineers when setting the treatment conditions.

PMID- 21961505
TI  - Mutations in WDR62 gene in Pakistani families with autosomal recessive primary
      microcephaly.
AB  - BACKGROUND: Autosomal recessive primary microcephaly is a disorder of neurogenic
      mitosis that causes reduction in brain size. It is a rare heterogeneous condition
      with seven causative genes reported to date. Mutations in WD repeat protein 62
      are associated with autosomal recessive primary microcephaly with cortical
      malformations. This study was initiated to screen WDR62 mutations in four
      consanguineous Pakistani families with autosomal recessive primary microcephaly.
      METHODS: As part of a large study to detect the genetic basis of primary
      microcephaly in Pakistan, homozygosity mapping and DNA sequencing was used to
      explore the genetic basis of autosomal recessive primary microcephaly in four
      families. RESULTS: Four out of 100 families recruited in the study revealed
      linkage to the MCPH2 locus on chromosome 19, which harbor WDR62 gene. DNA
      sequencing in these MCPH2 linked families result in the identification of a novel
      nonsense mutation (p.Q648X) and three previously known mutations. CONCLUSION: Our
      data indicate that WDR62 mutations cause about 4% of autosomal recessive primary
      microcephaly in Pakistan.

PMID- 21961506
TI  - Effect of physical exercise on bone density and remodeling in egyptian type 1
      diabetic osteopenic adolescents.
AB  - BACKGROUND: The study was planned to assess effect of physical exercise on bone
      remodeling in type I diabetics with osteopenia. METHODS: Twenty-four type I
      diabetes mellitus (DM1) with osteopenia (10 females and 14 males) were compared
      to thirty-eight age- and sex-matched healthy control individuals (20 females and
      18 males) for biochemical and radiologic parameters of bone mass. Laboratory
      investigations included serum and urinary calcium, inorganic phosphorus, alkaline
      phosphatase, and serum "procollagen type 1 N-terminal propeptide (P1NP). Bone
      densitometry was assessed at neck femur using Dual Energy X-ray Absorptiometry
      (DEXA). Serum P1NP and DEXA were reevaluated after a planned exercise program.
      RESULTS: Patients and controls were comparable with respect to serum as well as
      urinary biochemical parameters of bone mass namely; calcium, phosphorus and total
      serum alkaline phosphatase. Osteopenic DM1 patients displayed lower mean serum
      P1NP than control group (20.11 +/- 6.72 ug?dL versus 64.96 +/- 34.89 ug?dL; p <
      0.05). A significant correlation was observed between BMD and degree of glycemic
      control reflected by serum glycated hemoglobin (r = -0.44, p, 0.030). Bone
      densitometry correlated with serum P1NP (r = -0.508, p, 0.011). After a planned
      regular exercise for 3 months, serum P1NP and BMD levels increased with
      percentage change of 40.88 +/- 31.73 and 3.36 +/- 2.94, respectively. Five
      patients resumed normal densitometry and they were all males. CONCLUSION:
      Diabetic osteopenic patients displayed lower serum levels of procollagen type 1 N
      terminal propeptide which reflects poor bone formation. A 3-months planned
      exercise program was associated with improvement of bone densitometry and
      significant increment of serum P1NP.

PMID- 21961507
TI  - "So what", and the research question: tips for success in publishing.

PMID- 21961508
TI  - Optic disc dimensions and cup-disc ratios among healthy South Indians: The
      Chennai Glaucoma Study.
AB  - PURPOSE: To present optic disc and cup dimensions, cup-disc ratios (CDRs) and
      asymmetry among healthy South Indians, and their associations with ocular and
      systemic variables. METHODS: A total of 623 healthy phakic participants of the
      Chennai Glaucoma Study underwent complete eye examinations including optic disc
      stereo-photography. Planimetry was performed under stereo-viewing conditions. The
      morphological type of cupping (no cups, steep cups, partly sloping and fully
      sloping cups) was identified based on a modification of the classification by
      Jonas et al.( 11 ) The associations of planimetric measures (optic disc area, cup
      area and vertical cup-disc ratio [VCDR]) with age, gender, height, intraocular
      pressure, refraction, astigmatism, axial length and corneal thickness as
      explanatory variables were examined. The associations of asymmetries in the above
      planimetric measures with age, gender and asymmetries of the above explanatory
      variables were examined. RESULTS: Mean optic disc and cup areas were 2.82 +/-
      0.52 mm(2) and 0.53 +/- 0.39 mm(2). Mean CDR was 0.36 +/- 0.18. Men had larger
      discs (P = 0.03). Cup area and VCDR revealed significant associations with disc
      area (P <0.0001) and type of cupping (P < 0.0001). Mean disc and cup area
      asymmetries were 0.19 +/- 0.16 mm(2) and 0.15 +/- 0.15 mm(2). Mean VCDR asymmetry
      was 0.07 +/- 0.08 mm(2). Cup area and VCDR asymmetries showed significant
      associations with disc area asymmetry (P < 0.0001, both) and asymmetry in the
      presence or absence of physiological cupping, i.e. subjects with physiological
      cupping in one eye and no cupping in the other (P < 0.0001, both). CONCLUSIONS:
      We present normative optic disc, cup and VCDR measures and asymmetries among
      healthy South Indians. We demonstrated the dependence of VCDR on the
      morphological type of cupping.

PMID- 21961509
TI  - Heidelberg Retina Tomograph (HRT3) in population-based epidemiology: normative
      values and criteria for glaucomatous optic neuropathy.
AB  - PURPOSE: To establish normative values for Heidelberg Retina Tomograph (HRT3)
      variables and to develop HRT3-based criteria for glaucomatous optic neuropathy
      for epidemiological research in a white population. METHODS: Consecutive
      participants in the Rotterdam Study were examined with HRT and simultaneous
      stereoscopic fundus photography (ImageNet) in addition to other ophthalmic
      examinations including intraocular pressure (IOP) measurements and perimetry.
      Normative values for all HRT3 variables were determined in participants who met
      all the following criteria: no glaucomatous visual field loss (GVFL), an IOP of
      21mmHg or less, no IOP lowering treatment, and a negative family history of
      glaucoma. Sensitivity was determined in participants with glaucomatous visual
      field loss at a fixed high specificity of 97.5% - a value commonly used in
      population-based epidemiology. RESULTS: A total of 2516 participants were
      included in this study of whom 66 had glaucomatous visual field loss in at least
      one eye and 1680 fulfilled the criteria for contributing to the normative values.
      The HRT3 linear cup-disc ratio (LCDR) variable, adjusted for disc area, showed
      the highest sensitivity, 35%, at the required specificity of 97.5%. The 97.5th
      percentile of the LCDR was 0.67 for small discs (up to 1.5 mm(2)), 0.71
      [corrected] for medium-sized discs and 0.76 [corrected] for large discs (above
      2.0 mm(2)).The HRT3 Glaucoma Probability Score and previously published linear
      discriminant functions showed a lower sensitivity than LCDR at this specificity.
      CONCLUSIONS: At the high specificity of 97.5% as is commonly used in population
      based epidemiology, the sensitivity of the HRT3 is low - albeit not lower than
      that of the vertical cup-disc ratio as assessed with simultaneous stereoscopic
      fundus photography and analyzed with the ImageNet software. The LCDR variable,
      stratified for disc area, seems to be the most suitable variable to develop
      criteria for glaucomatous optic neuropathy for epidemiological purposes.

PMID- 21961510
TI  - Defining glaucomatous optic neuropathy from a continuous measure of optic nerve
      damage - the optimal cut-off point for risk-factor analysis in population-based
      epidemiology.
AB  - PURPOSE: Diseases characterized by a continuous trait can be defined by setting a
      cut-off point for the disease measure in question, accepting some
      misclassification. The 97.5th percentile is commonly used as a cut-off point.
      However, it is unclear whether this percentile is the optimal cut-off point from
      the point of view of risk-factor analysis. The optimal cut-off point for risk
      factor analysis can be found with a statistical method that minimizes the effect
      of misclassification. We applied this method to glaucomatous optic neuropathy.
      Here, the continuous trait is the cup-disc ratio. The aim of this study was to
      determine the optimal cup-disc ratio cut-off point for risk-factor analysis in
      population-based epidemiology. METHODS: All participants in the population-based
      Rotterdam Study underwent intraocular pressure (IOP) measurements, assessment of
      the cup-disc ratio with the Heidelberg Retina Tomograph (HRT) and visual field
      testing. In the statistical method, the cup-disc ratio (the continuous trait) and
      the IOP (a major risk factor) were independent variables and glaucomatous visual
      field loss (the true glaucoma endpoint) the dependent variable in a logistic
      regression model. The optimal cup-disc ratio cut-off point was found by
      minimizing the influence of IOP in this model. Variability of the approach was
      assessed by using a bootstrap resampling technique. RESULTS: Of 2444 included
      participants, 93 had glaucomatous visual field loss. The median optimal cup-disc
      ratio cut-off point was the 97.0th percentile with a 95% central range from 95.5
      to 98.5. CONCLUSION: The optimal cup-disc ratio cut-off point for risk-factor
      analysis is close to the commonly used 97.5th percentile.

PMID- 21961511
TI  - Primary angle closure glaucoma in East Asia: educational attainment as a
      protective factor.
AB  - PURPOSE: To examine the relationship between education, other risk factors and
      incident primary angle closure glaucoma (PACG). METHOD: Glaucoma was excluded in
      a group of 4597 Mongolian volunteers in 1999. After 6 years, 1892 traced
      participants had full ophthalmic examination, dilated disc photographs and agreed
      to complete a questionnaire on socio-economic status. PACG was diagnosed using
      both structural and functional evidence from objective grading of paired disc
      photographs, follow up visual fields and clinical examination. Ophthalmic
      examination included van Herick grading, Goldmann intraocular pressure (IOP),
      gonioscopy, lens opacity grading and dilated disc examination. Central anterior
      chamber depth, lens thickness and axial length were recorded using ultrasound A
      scan mounted on a slitlamp. Education level was assessed using national census
      categories. RESULTS: PACG was diagnosed in 29 participants (6 year incidence =
      1.53%, 95% confidence interval (CI) = 1.03-2.19%). In univariate analysis, risk
      factors for incident PACG included presence of refractive error, narrow van
      Herick grading of <=15%, narrower average Shaffer grading, higher IOP, larger cup
      disc ratio and lower levels of education. In multivariate analysis, adjusted for
      age, sex, Shaffer grading, refractive error and IOP, those with no formal
      education were approximately 7 times more likely to develop PACG compared to
      those with >8 years of formal schooling (OR = 7.27, 95% CI = 2.73-19.38).
      CONCLUSIONS: People with lower levels of education have a higher risk of incident
      PACG, independent of age, sex, IOP and axial length.

PMID- 21961512
TI  - Influence of family history as a risk factor on primary angle closure and primary
      open angle glaucoma in a Chinese population.
AB  - PURPOSE: To identify the likelihood of family history as a risk factor for the
      presence and severity of primary angle closure (PAC) and primary open angle
      glaucoma (POAG) in a Chinese population. METHODS: All participants were asked to
      complete a questionnaire and undergo a comprehensive eye examination. Past
      history of hypertension, diabetes mellitus, hyperopia, high myopia, and family
      history of glaucoma were recorded. For those patients with a family history of
      glaucoma, the relationship between the patient and the affected relatives has
      been specified. RESULTS: A total of 332 PAC patients, 228 POAG patients and 193
      controls were included. Of the 332 PAC patients, 83 (25.00%) had glaucoma family
      history. Characteristic-adjusted odds ratio (OR) of family history for PAC was
      4.82 [95% confidence interval (CI): 2.08-11.19] and for severity of PAC was 1.61
      (95% CI: 1.05-2.49). Among first-relatives only parents account for the family
      history rate of PAC [OR 8.76 (95% CI: 2.00-38.32)]. Of the 228 POAG patients, 49
      (21.49%) had a family history of glaucoma. Odds ratio for POAG was 8.38 (95% CI:
      3.33-21.07) and for severity of POAG was 1.81 (95% CI: 1.05-3.14). Unlike
      patients with PAC, only siblings and offspring account for the family history
      rate of POAG [OR 8.99 (95% CI: 2.38-33.99) and OR 19.23 (95% CI: 1.53-241.24)
      respectively]. CONCLUSION: Our study showed that a family history of glaucoma is
      associated with the presence and severity of PAC and POAG. This supports the
      finding that screening first-degree relatives will be an effective way to detect
      glaucoma in a population.

PMID- 21961513
TI  - Developing an algorithm to convert routine measures of vision into utility values
      for glaucoma.
AB  - PURPOSE: Measures of quality of life called utility values (UVs) are needed to
      deliver the most cost-effective health care for glaucoma patients. UVs are rarely
      measured in clinical research and practice whereas clinical outcomes such as
      visual field are routinely collected. The aim of this study was to develop an
      algorithm that calculates UVs directly from combinations of routine measures of
      binocular visual field, visual acuity, and contrast sensitivity. METHODS: A total
      of 132 outpatients with primary open angle glaucoma were recruited. The Time
      Trade-off (TTO) question was administered during face-to-face interviews.
      Binocular ETDRS logMAR visual acuity (VA(B)), binocular Pelli-Robson contrast
      sensitivity (CS(B)), and Humphrey 24-2 monocular visual field tests were
      performed on the same day. Integrated (binocular) visual field (IVF) scores were
      derived. Tobit regression analyses were used to model utility values based on
      combinations of IVF, VA(B), CS(B) and other controlling factors. RESULTS: UVs
      recorded for 123 cases correlated significantly with both clinical measures of
      binocular visual function (r = -0.47, IVF; r = -0.48, VA(B); r = 0.50, CS(B); P
      <0.0001) and measures of vision-specific quality of life (r = 0.54-0.6, P
      <0.0001). Two final models incorporate terms for IVF and VA(B), with or without
      living arrangements, and explain 22% and 31% of variation in utilities. CS(B) was
      not included in either model due to co-linearity between CS(B) and VA(B)
      confounding the models. CONCLUSION: The models provide preliminary algorithms for
      predicting the expected UVs for glaucoma populations directly from clinical
      outcomes collected routinely in clinical practice.

PMID- 21961514
TI  - Determinants and risk factors for central corneal thickness in Japanese persons:
      the Funagata Study.
AB  - PURPOSE: To examine the association between glucose metabolism and central
      corneal thickness (CCT) in Japanese adults. METHODS: A sub-sample of 322 Japanese
      adults participating in the Funagata Study was included in this analysis. CCT was
      measured using a specular microscope. Glucose metabolism was examined using 75-g
      oral glucose tolerance test. Mean differences in CCT (MUm) and 95% confidence
      intervals were estimated with univariate, age-sex-adjusted and multivariate
      models using multiple linear regression. RESULTS: The mean (+/- standard
      deviation) age of the study sample was 63.7 +/- 11.4 years and 44% were men. The
      mean fasting plasma glucose (FPG), 2-hour post-load plasma glucose (2hPG) and
      haemoglobin A1c (HbA1c) concentrations were 96.8 +/- 12.6mg/dl, 123.6 +/-
      41.2mg/dl and 5.3 +/- 0.4%, respectively. CCT was normally distributed in the
      study sample, and the mean CCT was 544.7 +/- 34.6MUm. After multivariate
      adjustment, characteristics associated with increased CCT were 2hPG and HbA1c
      concentrations, impaired glucose tolerance, diabetes, body weight or body mass
      index and current smoking. CONCLUSION: Impaired glucose tolerance, diabetes,
      obesity and current smoking are associated with increased CCT. Additional studies
      are required to examine whether interventions to affect these characteristics may
      reduce CCT.

PMID- 21961516
TI  - More than just talk: the framing of transactional sex and its implications for
      vulnerability to HIV in Lesotho, Madagascar and South Africa.
AB  - BACKGROUND: 'Transactional sex' was regarded by the mid-1990s as an important
      determinant of HIV transmission, particularly in sub-Saharan Africa. Little
      attention has been paid to what the terms used to denote transactional sex
      suggest about how it is understood. This study provides a nuanced set of
      descriptions of the meaning of transactional sex in three settings. Furthermore,
      we discuss how discourses around transactional sex suggest linkages to processes
      of globalization and hold implications for vulnerability to HIV. METHODS: The
      analysis in this article is based on three case studies conducted as part of a
      multi-country research project that investigated linkages between economic
      globalization and HIV. In this analysis, we contextualize and contrast the 'talk'
      about transactional sex through the following research methods in three study
      sites: descriptions revealed through semi-structured interviews with garment
      workers in Lesotho; focus groups with young women and men in Antananarivo,
      Madagascar; and focus groups and in-depth interviews with young women and men in
      Mbekweni, South Africa. RESULTS: Participants' talk about transactional sex
      reveals two themes: (1) 'The politics of differentiation' reflects how
      participants used language to demarcate identities, and distance themselves from
      contextually-based marginalized identities; and (2) 'Gender, agency and power'
      describes how participants frame gendered-power within the context of
      transactional sex practices, and reflects on the limitations to women's power as
      sexual agents in these exchanges. Talk about transactional sex in our study
      settings supports the assertion that emerging transactional sexual practices are
      linked with processes of globalization tied to consumerism. CONCLUSIONS: By
      focusing on 'talk' about transactional sex, we locate definitions of
      transactional sex, and how terms used to describe transactional sex are morally
      framed for people within their local context. We take advantage of an opportunity
      to comparatively explore such talk across three different study sites, and
      contribute to a better understanding of both emerging sexual practices and their
      implications for HIV vulnerability. Our work underlines that transactional sex
      needs to be reflected as it is perceived: something very different from, but of
      at least equal concern to, formal sex work in the efforts to curb HIV
      transmission.

PMID- 21961520
TI  - Clerodendron glandulosum.Coleb leaf extract attenuates in vitro macrophage
      differentiation and expression of VCAM-1 and P-selectin in thoracic aorta of
      atherogenic diet fed rats.
AB  - Present inventory evaluates the anti-atherogenic potential of C.
      glandulosum.Coleb leaf extract (CG) using in vivo and in vitro experimental
      models. Serum markers of low density lipoprotein (LDL-C) oxidation, cholesterol,
      triglycerides, lipoproteins, auto-antibody titer, ex vivo LDL-C oxidation, LDL-C
      aggregation, aortic lipids, histopathological evaluations and immunolocalization
      of macrophage surface marker (F4/80), vascular cell adhesion molecule-1 (VCAM-1)
      and P-selectin were performed in CON [rats treated with single dose of saline
      (i.p.) and fed with laboratory chow], ATH [rats treated with single dose of
      vitamin D3 (600,000 IU, i.p) and fed with atherogenic diet] and ATH+CG [rats
      treated with single dose of vitamin D3 (600,000 IU, i.p.) and fed with
      atherogenic diet and simultaneously treated with 200 mg/kg CG extract, p.o.] for
      8 weeks. CG extract supplementation to atherogenic diet fed rats significantly
      prevented increment in serum cholesterol, triglycerides, and lipoproteins,
      markers of LDL-C oxidation, auto-antibody titer and aortic lipids. Also, LDL-C
      isolated from ATH+CG rats recorded mimimal aggregation and susceptibility to
      undergo ex vivo LDL-C oxidation. Microscopic evaluation of thoracic aorta of
      ATH+CG rats reveled prevention of atheromatous plaque formation, accumulation of
      lipid laden macrophages, calcium deposition, distortion/defragmentation of
      elastin, accumulation of macrophages and, down regulation of cell adhesion
      molecules (VCAM-1 and P-selectin) expression. Further, in vitro monocyte to
      macrophage differentiation was significantly attenuated in presence of CG extract
      (200 ug/mL). It can be concluded from the present study that, CG extract is
      capable of controlling induction of experimental atherosclerosis and warrants
      further scrutiny at the clinical level as a possible therapeutic agent.

PMID- 21961521
TI  - Early gene expression changes with rush immunotherapy.
AB  - BACKGROUND: To examine whether whole genome expression profiling could reveal
      changes in mRNA expression of peripheral blood mononuclear cells (PBMC) from
      allergic patients undergoing rush immunotherapy (RIT) that might be manifest
      within the first few months of treatment. METHODS: For this study, PBMC from
      three allergic patients undergoing RIT were assessed at four timepoints: prior to
      RIT, at 1 week and 7 week post-RIT, during build-up and at 4 months, after
      establishment of a maintenance dose. PBMC mRNA gene expression changes over time
      were determined by oligonucleotide microarrays using the Illumina Human-6
      BeadChip Platform, which simultaneously interrogates expression profiles of >
      47,000 transcripts. Differentially expressed genes were identified using well
      established statistical analysis for microarrays. In addition, we analyzed
      peripheral blood basophil high-affinity IgE receptor (Fc epsilon RI) expression
      and T-regulatory cell frequency as detected by expression of CD3+CD4+CD25bright
      cells at each timepoint using flow cytometry. RESULTS: In comparing the initial 2
      timepoints with the final 2 timepoints and analyzing for genes with >=1.5-fold
      expression change (p less than or equal to 0.05, BH-FDR), we identified 507
      transcripts. At a 2-fold change (p less than or equal to 0.05, BH-FDR), we found
      44 transcripts. Of these, 28 were up-regulated and 16 were down-regulated genes.
      From these datasets, we have identified changes in immunologically relevant genes
      from both the innate and adaptive response with upregulation of expressed genes
      for molecules including IL-1beta, IL-8, CD40L, BTK and BCL6. At the 4 month
      timepoint, we noted a downward trend in Fc epsilon RI expression in each of the
      three patients and increased allergen-specific IgG4 levels. No change was seen in
      the frequency of peripheral T-regulatory cells expressed over the four
      timepoints. CONCLUSIONS: We observed significant changes in gene expression early
      in peripheral blood samples from allergic patients undergoing RIT. Moreover,
      serum levels for allergen specific IgG4 also increased over the course of
      treatment. These studies suggest that RIT induces rapid and dynamic alterations
      in both innate and adaptive immunity which can be observed in the periphery of
      allergic patients. These alterations could be directly related to the therapeutic
      shift in the allergen-specific class of immunoglobulin.

PMID- 21961522
TI  - Real-time label-free affinity biosensors for enumeration of total bacteria based
      on immobilized concanavalin A.
AB  - This work presents the results of the use of flow injection surface plasmon
      resonance and impedimetric affinity biosensors for detecting and enumerating
      total bacteria based on the binding between E. coli and Con A, immobilized on a
      modified gold electrode. The single analysis time for both techniques was less
      than 20 min. Dissociation between the immobilized Con A and the E. coli using 200
      mM of glucose in HCl at pH of 2.00 enabling the sensor to be reused for between
      29-35 times. Impedimetric detection provided a much lower limit of detection (12
      CFU mL(-1)) than the surface plasmon resonance method (6.1 * 10(7) CFU mL(-1)).
      Using the impedimetric system, real sample analysis was performed and the results
      were compared to the plate count agar method. Cell concentrations obtained by the
      biosensor were only slightly different from the result obtained from the plate
      count agar. The proposed system offers a rapid and useful tool for screening
      detection and enumeration of total bacteria.

PMID- 21961523
TI  - Autonomous nanomotor based on copper-platinum segmented nanobattery.
AB  - We describe an efficient, bubble-free nanoscale motor consisting of a copper
      platinum (Cu-Pt) segmented rod that operates as a nanobattery in dilute aqueous
      Br(2) or I(2) solutions. The motion of the rod is powered by self-electrophoresis
      caused by redox reactions occurring on the two different metal segments.
      Asymmetric ratchet-shaped pure copper nanorods were also found to rotate and
      tumble in aqueous Br(2) solution because of the ion gradient arising from
      asymmetric dissolution of copper.

PMID- 21961524
TI  - Upregulation of CYP 450s expression of immortalized hepatocyte-like cells derived
      from mesenchymal stem cells by enzyme inducers.
AB  - BACKGROUND: The strenuous procurement of cultured human hepatocytes and their
      short lives have constrained the cell culture model of cytochrome P450 (CYP450)
      induction, xenobiotic biotransformation, and hepatotoxicity. The development of
      continuous non-tumorous cell line steadily containing hepatocyte phenotypes would
      substitute the primary hepatocytes for these studies. RESULTS: The hepatocyte
      like cells have been developed from hTERT plus Bmi-1-immortalized human
      mesenchymal stem cells to substitute the primary hepatocytes. The hepatocyte-like
      cells had polygonal morphology and steadily produced albumin, glycogen, urea and
      UGT1A1 beyond 6 months while maintaining proliferative capacity. Although these
      hepatocyte-like cells had low basal expression of CYP450 isotypes, their
      expressions could be extensively up regulated to 80 folds upon the exposure to
      enzyme inducers. Their inducibility outperformed the classical HepG2 cells.
      CONCLUSION: The hepatocyte-like cells contained the markers of hepatocytes
      including CYP450 isotypes. The high inducibility of CYP450 transcripts could
      serve as a sensitive model for profiling xenobiotic-induced expression of CYP450.

PMID- 21961525
TI  - Tic20 forms a channel independent of Tic110 in chloroplasts.
AB  - BACKGROUND: The Tic complex (Translocon at the inner envelope membrane of
      chloroplasts) mediates the translocation of nuclear encoded chloroplast proteins
      across the inner envelope membrane. Tic110 forms one prominent protein
      translocation channel. Additionally, Tic20, another subunit of the complex, was
      proposed to form a protein import channel - either together with or independent
      of Tic110. However, no experimental evidence for Tic20 channel activity has been
      provided so far. RESULTS: We performed a comprehensive biochemical and
      electrophysiological study to characterize Tic20 in more detail and to gain a
      deeper insight into its potential role in protein import into chloroplasts.
      Firstly, we compared transcript and protein levels of Tic20 and Tic110 in both
      Pisum sativum and Arabidopsis thaliana. We found the Tic20 protein to be
      generally less abundant, which was particularly pronounced in Arabidopsis.
      Secondly, we demonstrated that Tic20 forms a complex larger than 700 kilodalton
      in the inner envelope membrane, which is clearly separate from Tic110, migrating
      as a dimer at about 250 kilodalton. Thirdly, we defined the topology of Tic20 in
      the inner envelope, and found its N- and C-termini to be oriented towards the
      stromal side. Finally, we successfully reconstituted overexpressed and purified
      full-length Tic20 into liposomes. Using these Tic20-proteoliposomes, we could
      demonstrate for the first time that Tic20 can independently form a cation
      selective channel in vitro. CONCLUSIONS: The presented data provide first
      biochemical evidence to the notion that Tic20 can act as a channel protein within
      the chloroplast import translocon complex. However, the very low abundance of
      Tic20 in the inner envelope membranes indicates that it cannot form a major
      protein translocation channel. Furthermore, the independent complex formation of
      Tic20 and Tic110 argues against a joint channel formation. Thus, based on the
      observed channel activity of Tic20 in proteoliposomes, we speculate that the
      chloroplast inner envelope contains multiple (at least two) translocation
      channels: Tic110 as the general translocation pore, whereas Tic20 could be
      responsible for translocation of a special subset of proteins.

PMID- 21961526
TI  - Amine metabolomics of hyperglycemic endothelial cells using capillary LC-MS with
      isobaric tagging.
AB  - Intracellular amine metabolite changes were quantified from hyperglycemic human
      aortic endothelial cells (HAECs) as a model for macrovascular complications of
      diabetes. Amines were selectively tagged using the N-hydroxysuccinimide ester
      (NHS) based isobaric tag DiART (Deuterium isobaric Amine Reactive Tag),
      synthesized in house. DiART labeling improved chromatographic resolution of
      derivatized amines, resulted in 100-fold signal-to-noise enhancement in mass
      spectrometry (MS) analyses, and allowed multiplex quantification of four samples
      concurrently through tandem MS fragmentation. Targeted measurement of 31 DiART
      tagged amines demonstrated the limits of detection below 10 nM/100 amol and
      averaged RSDs less than 5%. Examination of endothelial cells exposed to short
      term hyperglycemia resulted in significant changes to alanine, proline, glycine,
      serine, and glutamine compared to osmotic controls. Discovery of proline
      elevation in hyperglycemic endothelial cells suggests a role of proline in
      hyperglycemia-mediated oxidative stress. Exposure of endothelial cells to high
      glucose for 7 days resulted in reduced cell number and significant changes to 21
      amines relative to cell number. Prominent amine elevation from long-term
      hyperglycemia include aminoadipate as a sign of lysine breakdown through
      oxidative stress; cystathionine, hypotaurine, and proline indicating an
      antioxidant response; and glutamine/glutamate as substrate level activators of
      additional metabolic pathways. This report is the first investigation of amine
      changes to hyperglycemic endothelial cells and offers new insights into the
      pathophysiology of diabetic complications.

PMID- 21961527
TI  - Distinguishing amyloid fibril structures in Alzheimer's disease (AD) by two
      dimensional ultraviolet (2DUV) spectroscopy.
AB  - Understanding the aggregation mechanism of amyloid fibrils and characterizing
      their structures are important steps in the investigation of several
      neurodegenerative disorders associated with the misfolding of proteins. We report
      a simulation study of coherent two-dimensional chiral signals of three NMR
      structures of Abeta protein fibrils associated with Alzheimer's Disease, two
      models for Abeta(8-40) peptide wild-type (WT) and one for the Iowa (D23N)
      Abeta(15-40) mutant. Both far-ultraviolet (FUV) signals (lambda = 190-250 nm),
      which originate from the backbone npi* and pipi* transitions, and near
      ultraviolet (NUV) signals (lambda >= 250 nm) associated with aromatic side chains
      (Phe and Tyr) show distinct cross-peak patterns that can serve as novel
      signatures for the secondary structure.

PMID- 21961528
TI  - Technical, economical, and climate-related aspects of biochar production
      technologies: a literature review.
AB  - For the development of commercial biochar projects, reliable data on biochar
      production technologies is needed. For this purpose, peer-reviewed scientific
      articles on carbonization technologies (pyrolysis, gasification, hydrothermal
      carbonization, and flash carbonization) have been analyzed. Valuable information
      is provided by papers on pyrolysis processes, less information is available on
      gasification processes, and few papers about hydrothermal and flash carbonization
      technologies were identified. A wide range of data on the costs of char
      production (between 51 US$ per tonne pyrolysis biochar from yard waste and 386
      US$ per tonne retort charcoal) and on the GHG balance of biochar systems (between
      -1054 kg CO(2)e and +123 kg CO(2)e per t dry biomass feedstock) have been
      published. More data from pilot projects are needed to improve the evaluation of
      biochar production technologies. Additional research on the influence of biochar
      application on surface albedo, atmospheric soot concentration, and yield
      responses is necessary to assess the entire climate impact of biochar systems.
      Above all, further field trials on the ability of different technologies to
      produce chars for agricultural soils and carbon sequestration are essential for
      future technology evaluation.

PMID- 21961529
TI  - Investigational CETP antagonists for hyperlipidemia and atherosclerosis
      prevention.
AB  - INTRODUCTION: Reverse cholesterol transport (RCT) is a function of high-density
      lipoproteins (HDL) in humans and higher species. It is enabled by the cholesteryl
      ester transfer protein (CETP), a high molecular weight protein exchanging
      cholesteryl esters in HDL for triglycerides in very low-density lipoproteins
      (VLDL). Inhibition of CETP may provide a useful strategy to raise HDL, the
      protective lipoprotein fraction in plasma. AREAS COVERED: Evaluation based on
      clinical and experimental findings of the three drugs developed or in advanced
      development for CETP inhibition. EXPERT OPINION: Inhibition of CETP, both
      inherited and drug induced, at times leads to dramatic elevations of HDL
      cholesterol (HDL-C) levels. Epidemiological data presently available do not,
      however, provide convincing evidence that reduced CETP levels or activity due to
      genetic factors and associated with HDL-C elevations, reduce cardiovascular risk.
      Indeed, the opposite may be true in some instances. All the three CETP inhibitors
      were the object of experimental and clinical evaluation. Large clinical trials
      with torcetrapib led to very negative findings, that is, raised cardiovascular
      morbidity and mortality in addition to raised risk of cancer and sepsis. Off
      target effects of the drug, such as aldosterone retention and raised blood
      pressure, were believed to provide an explanation for these negative findings.
      The two newer agents, dalcetrapib and anacetrapib, do not exert off-target
      effects. The two drugs differ because anacetrapib has a more dramatic effect on
      HDL cholesterolemia (+139%) versus more moderate effects of dalcetrapib (+20
      30%). Anacetrapib, however, may impair formation of pre-beta HDL, that is, the
      primary particles in the process of cholesterol removal. The initial large trial
      with anacetrapib (DEFINE study) in coronary patients on statin treatment,
      appeared to confirm a remarkable HDL raising property, together with some
      reduction in vascular end points, in particular coronary procedures. The issue of
      other potentially harmful effects of CETP inhibition (sepsis and others) has yet
      to be clarified. Large clinical end-point trials, however, will be necessary to
      provide convincing evidence that, in addition to raising HDL-C, CETP inhibitors
      provide a valid additional treatment, for example, to statins in patients with
      coronary heart disease (CHD) or at high risk of CHD.

PMID- 21961530
TI  - A high throughput in vitro mrp2 assay to predict in vivo biliary excretion.
AB  - Prediction of biliary excretion is a challenge for drug discovery scientists due
      to the lack of in vitro assays. This study explores the possibility of
      establishing a simple assay to predict in vivo biliary excretion via the mrp2
      transport system. In vitro mrp2 activity was determined by measuring the ATP
      dependent uptake of 5(6)-carboxy-2',7'-dichlorofluorescein (CDCF) in canalicular
      plasma membrane vesicles (cLPM) from rat livers. The CDCF uptake was time- and
      concentration-dependent (K(m) of 2.2 +/- 0.3 uM and V(max) of 115 +/- 26
      pmol/mg/min) and strongly inhibited by the mrp2 inhibitors, benzbromarone, MK
      571, and cyclosporine A, with IC(50) values <= 1.1 uM. Low inhibition of CDCF
      uptake by taurocholate (BSEP inhibitor; 57 uM) and digoxin (P-gp inhibitor; 101
      uM) demonstrated assay specificity towards mrp2. A highly significant correlation
      (r(2) = 0.959) between the in vitro IC(50) values from the described mrp2 assay
      and in vivo biliary excretion in rats was observed using 10 literature compounds.
      This study demonstrated, for the first time, that a high throughput assay could
      be established with the capability of predicting biliary excretion in the rat
      using CDCF as a substrate.

PMID- 21961531
TI  - Stability of amino acids and their oligomerization under high-pressure
      conditions: implications for prebiotic chemistry.
AB  - The polymerization of amino acids leading to the formation of peptides and
      proteins is a significant problem for the origin of life. This problem stems from
      the instability of amino acids and the difficulty of their oligomerization in
      aqueous environments, such as seafloor hydrothermal systems. We investigated the
      stability of amino acids and their oligomerization reactions under high
      temperature (180-400 degrees C) and high-pressure (1.0-5.5 GPa) conditions, based
      on the hypothesis that the polymerization of amino acids occurred in marine
      sediments during diagenesis and metamorphism, at convergent margins on early
      Earth. Our results show that the amino acids glycine and alanine are stabilized
      by high pressure. Oligomers up to pentamers were formed, which has never been
      reported for alanine in the absence of a catalyst. The yields of peptides at a
      given temperature and reaction time were higher under higher-pressure conditions.
      Elemental, infrared, and isotopic analyses of the reaction products indicated
      that deamination is a key degradation process for amino acids and peptides under
      high-pressure conditions. A possible NH(3)-rich environment in marine sediments
      on early Earth may have further stabilized amino acids and peptides by inhibiting
      their deamination.

PMID- 21961532
TI  - Palladium-catalyzed coupling of arene C-H bonds with methyl- and arylboron
      reagents assisted by the removable 2-pyridylsulfinyl group.
AB  - The Pd(II)-catalyzed direct coupling of arene C-H bonds with organoboron reagents
      assisted by the 2-pyridylsulfinyl group is reported. Methylboronic acid and
      arylboronic acid neopentyl esters proved to be efficient coupling partners,
      furnishing methylated arenes and biaryl products in moderate to good yields. The
      2-pyridylsulfinyl group can be easily removed to provide the free biaryls. The
      essential role of the 2-pyridyl unit in stabilizing the cyclopalladation complex
      was demonstrated by X-ray diffraction analysis of the palladacycle intermediate.

PMID- 21961533
TI  - Automated ERCC1 immunochemistry on hybrid cytology/tissue microarray of malignant
      effusions: evaluation of antibodies 8F1 and D-10.
AB  - BACKGROUND: The excision repair cross-complementation group 1 (ERCC1) protein is
      the key enzyme of the nucleotide excision repair (NER) pathway. Loss of protein
      expression on immunohistochemistry is predictive for platinum-based chemotherapy
      response. Frequently, the diagnosis of malignancy is made on cytologic effusion
      samples. Therefore, we evaluated the staining quality of monoclonal anti-ERCC1
      antibodies 8F1 and D-10 on microarrays of malignant pleural and peritoneal
      effusions by automated immunochemistry. METHODS: Cores from effusion cell blocks
      of 117 patients with > 40 malignant cell clusters per whole section (pleural n =
      75, peritoneal n = 42) were assembled together with 30 histologic control cores
      from large tissue blocks (lung, breast and ovarian carcinoma, each n = 10) on
      hybrid cytology-tissue microarrays (C/TMA). Four immunochemistry protocols (Mab
      8F1 and D-10, CC1-mono Ventana and H2-60 Bond automat) were performed.
      Immunoreactivity was semi-quantitatively scored for intensity and intensity
      multiplied by percentage staining (H-score). RESULTS: Tumors were classified into
      female genital tract carcinoma (n = 39), lung adenocarcinoma (n = 23),
      mesothelioma (n = 15), unknown primary (n = 14), breast carcinoma (n = 10),
      gastro-intestinal carcinoma (n = 12) and other (n = 4). On both platforms,
      reproducible nuclear ERCC1 immunoreactivity was achieved with both antibodies,
      although D-10 was slightly weaker and presented more background staining as well
      as more variation in the low expression range. No significant differences were
      found between cytologic and histologic cores. Using the 8F1 CC1-mono protocol,
      lung and breast carcinomas had lower ERCC1 expression in comparison to the other
      entities (p-value < 0.05). CONCLUSIONS: Cytology microarrays (CMA) are suitable
      for investigation of clinical biomarkers and can be combined with conventional
      TMA's. Dichotomization of ERCC1 immunoreactivity scores is most suitable for
      patient stratification since definition of negativity is antibody-dependent.

PMID- 21961534
TI  - Exercise in pregnant women and birth weight: a randomized controlled trial.
AB  - BACKGROUND: Birth weight plays an important role in infant mortality and
      morbidity, childhood development, and adult health. To date there are
      contradictory results regarding the role of physical activity on birth weight. In
      addition, it is questioned whether exercise during second and third trimesters of
      pregnancy might affect gestational age and increase the risk of preterm delivery.
      Hence, the purpose of this study was to examine the effect of a supervised
      exercise-program on birth weight, gestational age at delivery and Apgar-score.
      METHODS: Sedentary, nulliparous pregnant women (N = 105), mean age 30.7 +/- 4.0
      years, pre-pregnancy BMI 23.8 +/- 4.3 were randomized to either an exercise group
      (EG, n = 52) or a control group (CG, n = 53). The exercise program consisted of
      supervised aerobic dance and strength training for 60 minutes, twice per week for
      a minimum of 12 weeks, with an additional 30 minutes of self-imposed physical
      activity on the non-supervised week-days. RESULTS: There was no statistically
      significant difference between groups in mean birth weight, low birth weight (<
      2500 g) or macrosomia (>= 4000 g). Per protocol analyses showed higher Apgar
      score (1 min) in the EG compared with the CG (p = 0.02). No difference was seen
      in length of gestation. CONCLUSION: Aerobic-dance exercise was not associated
      with reduction in birth weight, preterm birth rate or neonatal well-being.

PMID- 21961535
TI  - High-performance triisopropylsilylethynyl pentacene transistors via spin coating
      with a crystallization-assisting layer.
AB  - The effects of spin speed and an amorphous fluoropolymer (CYTOP)-patterned
      substrate on the crystalline structures and device performance of
      triisopropylsilylethynyl pentacene (TIPS-PEN) organic field-effect transistors
      (OFETs) were investigated. The crystallinity of the TIPS-PEN film was enhanced by
      decreasing the spin speed, because slow evaporation of the solvent provided a
      sufficient time for the formation of thermodynamically stable crystalline
      structures. In addition, the adoption of a CYTOP-patterned substrate induced the
      three-dimensional (3D) growth of the TIPS-PEN crystals, because the patterned
      substrate confined the TIPS-PEN molecules and allowed sufficient time for the
      self-organization of TIPS-PEN. TIPS-PEN OFETs fabricated at a spin speed of 300
      rpm with a CYTOP-patterned substrate showed a field-effect mobility of 0.131
      cm(2) V(-1) s(-1), which is a remarkable improvement over previous spin-coated
      TIPS-PEN OFETs.

PMID- 21961536
TI  - "Cofactor"-controlled enantioselective catalysis.
AB  - We report an achiral bisphosphine rhodium complex equipped with a binding site
      for the recognition of chiral anion guests. Upon binding small chiral guests-
      cofactors--the rhodium complex becomes chiral and can thus be used for asymmetric
      catalysis. Screening of a library of cofactors revealed that the best cofactors
      lead to hydrogenation catalysts that form the products with high
      enantioselectivity (ee's up to 99%). Interestingly, a competition experiment
      shows that even in a mixture of 12 cofactors high ee is obtained, indicating that
      the complex based on the best cofactor dominates the catalysis.

PMID- 21961537
TI  - Father of neurosurgery: Harvey Cushing's early experience with a pediatric
      brainstem glioma at the Johns Hopkins Hospital.
AB  - OBJECT: The early 20th century posed several challenges in the diagnosis and
      surgical treatment of intracranial tumors. However, this was a time in which more
      information was becoming more readily available based on pathological examination
      and surgical case reports. Such early work was crucial in shaping the current
      understanding of the nervous system and in developing modern treatment
      strategies. An early historical overview of the diagnosis and surgical
      interventions in pediatric patients with brainstem gliomas has not been
      described. Furthermore, Dr. Harvey Cushing's contributions to this field have not
      been reported. METHODS: Following institutional review board approval, and
      through the courtesy of the Alan Mason Chesney Archives, the authors reviewed the
      Johns Hopkins Hospital surgical files dating from 1896 to 1912. RESULTS: The
      authors describe Cushing's early experience with a pediatric brainstem glioma
      during his time as a young attending physician at the Johns Hopkins Hospital. The
      case, presented in 1909, described the clinical events in a 15-year-old
      schoolgirl who presented with signs of a cerebellopontine lesion. A suboccipital
      exploration was performed by Cushing; his findings and surgical approach are
      described. CONCLUSIONS: Harvey Cushing's early contributions to the field of
      pediatric neurosurgery, and to the operative treatment of pediatric brainstem
      gliomas have remained largely unknown. The case presented here represents the
      early work of the American "Father of Neurosurgery."

PMID- 21961538
TI  - Concomitant intraventricular colloid cyst and low-grade astrocytoma of the
      brainstem in a 16-year-old boy.
AB  - Multiple primary brain tumors are commonly observed in patients with a history of
      brain radiation therapy or neurofibromatosis. The concomitant presence of 2
      different types of brain tumors in a single location or chamber is a very rare
      clinical presentation in the absence of such a predisposing factor. The authors
      report on the case of a 16-year-old boy presenting with different types of brain
      tumors in 2 ventricular chambers concomitantly. This boy had a medium-sized
      colloid cyst of the third ventricle and a large fibrillary astrocytoma fungating
      from the brainstem into the floor of the fourth ventricle. The lesions were
      successfully excised in 2 separate surgeries. Radiotherapy was used as the
      adjuvant mode of therapy. There has been no sign of tumor recurrence after 16
      months of follow-up. Clinical awareness and recognition of such a combination of
      tumors is important because they will dictate special treatment strategies
      depending on the individual biological aggressiveness of each tumor.

PMID- 21961539
TI  - Intracerebral malignant peripheral nerve sheath tumor in a child with
      neurofibromatosis Type 1 and middle cerebral artery aneurysm treated with
      endovascular coil embolization.
AB  - Among the neoplastic conditions that affect patients with neurofibromatosis Type
      1 (NF1) are malignant peripheral nerve sheath tumors (MPNSTs), which typically
      arise from peripheral nerves of the limbs, trunk, and lumbar and brachial
      plexuses. Ionizing radiation is an established risk factor for MPNST development,
      especially in susceptible patients such as those with NF1. Patients with NF1 are
      also at risk for intracranial aneurysms, which are increasingly being
      successfully managed with endovascular therapies. The authors describe the case
      of a 9-year-old, previously healthy girl who presented in extremis with a right
      frontal intracerebral hemorrhage resulting from a ruptured right middle cerebral
      artery (MCA) trifurcation aneurysm. Following urgent decompressive craniectomy,
      the patient underwent endovascular coil embolization of the MCA aneurysm without
      complication. Given her mother's history of NF1, the child underwent genetic
      testing, which disclosed signs positive for NF1. The patient recovered well, but
      follow-up MR imaging and MR angiography performed at 14 months demonstrated a
      large frontotemporal mass encasing the right MCA trifurcation. The patient
      underwent frontotemporal craniotomy and subtotal resection of the mass, which was
      histologically found to be an intracranial MPNST. The patient received
      chemotherapy and focal radiation therapy and remains alive at 6 months
      postresection. To the authors' knowledge, this represents the only known case of
      intracranial neoplasm arising in the region of an intracranial aneurysm repaired
      by endovascular coil embolization. While patients with NF1 represent a population
      with genetic susceptibility to radiation-induced tumors, the pathogenesis of
      intracerebral MPNSTs remains poorly understood.

PMID- 21961540
TI  - Atlantal hemi-rings and craniocervical instability: identification, clinical
      characteristics, and management.
AB  - OBJECT: Congenital craniovertebral anomalies are relatively common, but anomalies
      leading to overt craniocervical instability may be difficult to recognize and
      treat. The authors present a series of patients with atlantal hemi-rings, a
      disorder resulting in congenital craniovertebral instability. Presentation,
      treatment, imaging, and follow-up data obtained in patients with atlantal hemi
      rings were assessed to identify factors relevant to craniocervical instability.
      METHODS: Nineteen patients were identified with atlantal hemi-rings, defined as a
      bony discontinuity of the C-1 ring in conjunction with lateral displacement of
      the C-1 lateral masses (as seen on coronal CT scans). Clinical and radiological
      characteristics were analyzed, including patient age at presentation, extent of
      occipitocervical motion, amount of C-1 lateral mass displacement, associated
      craniocervical anomalies, integrity of the transverse ligament, and neurological
      status. RESULTS: The mean patient age at presentation was 22 months (range birth
      to 9 years). The mean amount of occipitocervical translation seen on dynamic
      imaging was 9 mm (range 2-20 mm). Four patients required occipitocervical fusion
      at presentation. The remaining 15 patients were monitored for a mean of 20
      months, and 9 ultimately underwent fusion. Surgery was also recommended for 4 of
      the remaining 6 children. CONCLUSIONS: This report describes the radiological and
      clinical characteristics of patients with atlantal hemirings and craniocervical
      instability. The authors believe that this anomaly is the underlying cause of
      progressive instability in a significant proportion of patients with
      craniocervical abnormalities. The presence of atlantal hemi-rings should prompt
      immediate and thorough neurosurgical evaluation.

PMID- 21961541
TI  - C1-2 instability from os odontoideum mimicking intramedullary spinal cord tumor.
AB  - Os odontoideum is a common cause of atlantoaxial instability in the pediatric
      population. The authors present the cases of 2 patients whose initial clinical
      presentation and MR imaging findings were suggestive of an intramedullary
      neoplasm, but whose ultimate diagnosis was determined to be cervical spine
      instability and cord injury due to os odontoideum.

PMID- 21961542
TI  - Giant cell tumor of the odontoid in an adolescent male: radiation, chemotherapy,
      and resection for recurrence with 10-year follow-up.
AB  - Giant cell tumors (GCTs) are rare lesions of the cervical spine, with only 14
      previously reported pediatric cases in the literature, all occurring in females.
      The authors present the case of a 15-year-old boy with neck pain who was found to
      have a lytic GCT of the odontoid process. Following resection, recurrent disease
      was treated with radiotherapy and chemotherapy and then a final resection. He has
      remained tumor free for more than 10 years. The rarity of GCTs can make their
      diagnosis difficult in the cervical spine. Because of their aggressive behavior
      and relative resistance to adjuvant therapy, GCTs must be monitored diligently
      and treated aggressively.

PMID- 21961543
TI  - Congenital stridor in the context of Chiari malformation type II: the etiological
      role of vernix caseosa granulomatous meningitis.
AB  - The authors describe the case of a late preterm infant girl who presented
      prenatally with a low lumbar neural tube defect and features of Chiari
      malformation type II (CM-II). At birth, she exhibited stridor and underwent
      surgical repair of a lumbosacral myelomeningocele on Day 2 of life. The prognosis
      was deemed to be poor, and hence a "Chiari decompression" procedure was not
      undertaken. The patient was subsequently extubated and died on Day 10. Postmortem
      findings included a rarely described but characteristic granulomatous meningitic
      reaction to vernix caseosa, which presumably entered the subarachnoid space and
      spinal cord syrinx antenatally via the open neural tube defect. The significance
      of congenital stridor in the context of CM-II and in particular the role of
      vernix caseosa granulomatous meningitis are examined. The antenatal repair of
      myelomeningoceles, as championed by some, may prevent this ominous meningitic
      complication.

PMID- 21961544
TI  - Management of Dandy-Walker complex-associated infant hydrocephalus by combined
      endoscopic third ventriculostomy and choroid plexus cauterization.
AB  - OBJECT: Dandy-Walker complex (DWC) is a continuum of congenital anomalies
      comprising Dandy-Walker malformation (DWM), Dandy-Walker variant (DWV), Blake
      pouch cyst, and mega cisterna magna (MCM). Hydrocephalus is variably associated
      with each of these, and DWC-associated hydrocephalus has mostly been treated by
      shunting, often with 2-compartment shunting. There are few reports of management
      by endoscopic third ventriculostomy (ETV). This study is the largest series of
      DWC or DWM-associated hydrocephalus treated by ETV, and the first report of
      treatment by combined ETV and choroid plexus cauterization (ETV/CPC) in young
      infants with this association. METHODS: A retrospective review of the CURE
      Children's Hospital of Uganda clinical database between 2004 and 2010 identified
      45 patients with DWC confirmed by CT scanning (25 with DWM, 17 with DWV, and 3
      with MCM) who were treated for hydrocephalus by ETV/CPC. Three were excluded
      because of other potential causes of hydrocephalus (2 postinfectious and 1
      posthemorrhagic). RESULTS: The median age at treatment was 5 months (88% of
      patients were younger than 12 months). There was a 2.4:1 male predominance among
      patients with DWV. An ETV/CPC (ETV only in one) was successful with no further
      operations in 74% (mean and median follow-up 24.2 and 20 months, respectively
      [range 6-65 months]). The rate of success was 74% for DWM, 73% for DWV, and 100%
      for MCM; 95% had an open aqueduct, and none required posterior fossa shunting.
      CONCLUSIONS: Endoscopic treatment of DWC-associated hydrocephalus should be
      strongly considered as the primary management in place of the historical standard
      of creating shunt dependence.

PMID- 21961545
TI  - Features of the lumbar spine on magnetic resonance images following sectioning of
      filum terminale.
AB  - OBJECT: Spinal cord tethering due to a thickened filum terminale is a well
      described entity that can be treated surgically. Postoperative MR imaging of the
      lumbar spine is performed for unrelated issues or for the development of new
      symptoms suggestive of cord retethering. A lack of radiological criteria for
      successful detethering makes interpretation of postoperative MR images
      challenging. The delineation of postoperative radiological characteristics of a
      sectioned filum terminale is therefore valuable to clinicians managing these
      often complex cases. METHODS: The clinical data for 16 patients who underwent
      sectioning of a fatty and thickened filum between 2001 and 2010 and in whom pre-
      and postoperative MR imaging studies were available were analyzed. Medical
      records were interrogated for preoperative neurological examination, operative
      details, and postoperative follow-up. The MR images were examined by both a
      neurosurgeon and a neuroradiologist to assess postoperative radiological
      characteristics. RESULTS: The patients' age at time of surgery ranged from 0.3 to
      19.8 years (mean 7.5 years). Postoperative MR imaging was performed between 0.03
      and 7.36 years after the procedure (mean 2.5 years). Indications for
      postoperative imaging included new neurological symptoms (11 of 16 patients),
      routine interval imaging (3 of 16), and possible development of pseudomeningocele
      (2 of 16). Filum discontinuity was confirmed in 79% of cases postoperatively.
      Filum remnants appeared thicker after surgery in most cases (80%), a phenomenon
      most often appreciated in the cephalad end of the sectioned filum.
      Postoperatively, the conus was elevated in 5 cases (31%) and was found to be more
      ventrally located in 7 cases (44%). CONCLUSIONS: Discontinuity, along with
      thickening of the upper and lower remnants of a sectioned filum, may constitute
      important radiological features of a detethered filum. Radiological signs of
      conus relaxation, signified by elevation or a more ventral position, although
      reassuring, were less reliably observed postoperatively. Because it may be
      difficult to know if the goals of surgery were met on purely clinical grounds in
      this patient population, knowledge of the postoperative characteristics of a
      sectioned filum may aid the practicing neurosurgeon in the management of these
      complex cases.

PMID- 21961546
TI  - Single-incision laparoscopic transumbilical shunt placement.
AB  - Ventriculoperitoneal (VP) shunt placement is the most common surgical treatment
      for hydrocephalus. Laparoscopic techniques to aid in the placement of the
      peritoneal portion have been reported previously. Laparoscopic shunt placement
      has been associated with decreased operating time, less blood loss, and shorter
      hospital stays. The authors describe a single-incision laparoscopic shunt (SILS)
      insertion technique that facilitates directed placement of the peritoneal portion
      of the catheter in children. A total of 6 pediatric patients underwent the SILS
      procedure between December 2008 and March 2009. This cohort included 5 girls and
      1 boy; the average age was 6 years (range 1 day-16 years). One patient had
      previously undergone a VP shunt placement, but all other patients were undergoing
      the initial creation of their shunt. The most common pathological condition
      encountered was posttraumatic hydrocephalus (2 patients). All patients underwent
      successful placement of the peritoneal catheters. All catheters were seen to have
      CSF flowing freely within the peritoneal space.   The authors' recent experience
      shows that SILS placement is safe and feasible in children. It allows accurate,
      directed placement of the VP shunt with a single, almost invisible, umbilical
      incision. The shunt tubing is remote from this incision.

PMID- 21961547
TI  - Technique for insertion of intraventricular baclofen catheters.
AB  - Intraventricular baclofen (IVB) infusion has been used recently to treat
      secondary dystonia. Techniques of catheter implantation have not been thoroughly
      described. The object of this study was to describe a technique developed in the
      past 6 years to implant intraventricular catheters for baclofen infusion. Thirty
      one patients underwent endoscopic placement of intraventricular catheters for
      IVB, primarily patients whose anatomy made implantation of intrathecal catheters
      difficult or inappropriate. Using the technique described, catheters were
      successfully inserted into the desired ventricular location in each patient.
      Catheters remained in the desired location in 29 of 31 cases. Catheters can be
      inserted into the cerebral ventricles for infusion of baclofen. The technique
      described herein has been associated with few complications.

PMID- 21961548
TI  - Comparison of Hydrocephalus Outcome Questionnaire scores to neuropsychological
      test performance in school-aged children.
AB  - OBJECT: The Hydrocephalus Outcome Questionnaire (HOQ) is an established means of
      measuring quality of life, but the cognitive component of this questionnaire has
      never been formally compared with gold-standard neuropsychological test scores.
      The authors hypothesized that the HOQ Cognitive Health score would demonstrate a
      relatively strong correlation with neuropsychological test scores, whereas much
      weaker correlations would be seen for HOQ Physical and Social-Emotional Health
      scores. METHODS: A cross-sectional study of children with long-standing
      hydrocephalus presenting to The Hospital for Sick Children's Neurosurgery Clinic
      was performed between July 2006 and September 2008. Participating children and
      families completed the HOQ and a battery of 21 standard neuropsychological tests
      and questionnaires. Pearson correlation analysis was then performed. RESULTS: A
      total of 83 patients (81% participation) was accrued; the mean age was 11.5 +/-
      3.4 years (mean +/- SD) at the time of assessment. The mean age at hydrocephalus
      treatment was 1.3 +/- 2.6 years. The mean overall HOQ score was 0.69 +/- 0.21.
      The HOQ Cognitive score had a moderate or strong correlation with 19 (90%) of 21
      neuropsychological test scores, much more so than the HOQ Social-Emotional score
      (5 moderate or strong correlations, 24%) and the HOQ Physical score (1 moderate
      correlation, 5%). For 19 neuropsychological tests (90%), the HOQ Cognitive score
      had a stronger correlation than the other scores. The HOQ Cognitive score had
      particularly strong correlations with the Verbal IQ, List Learning, Behavior
      Problems, and Metacognitive Abilities components. CONCLUSIONS: Data from a wide
      ranging representative sample of children with long-standing hydrocephalus
      provide added evidence of the validity of the HOQ Cognitive score and the overall
      domain structure of the HOQ itself.

PMID- 21961549
TI  - Chronic granulomatous herpes encephalitis: a rare entity posing a diagnostic
      challenge.
AB  - Herpesviruses can cause an acute, subacute, or chronic disease state in both
      immunocompetent and immunocompromised individuals. Herpes simplex virus (HSV)
      encephalitis is most often an acute monophasic disease process. Rarely, however,
      it may progress to a chronic state, and more rarely still to a granulomatous
      encephalitis. Prior studies have suggested that antiviral immunity with Toll-like
      receptors determines susceptibility to herpesviruses. The authors report the case
      of a 14-year-old girl with a remote history of treated HSV encephalitis, who had
      intractable seizures and worsening MR imaging changes that were concerning for
      either a neoplastic or an inflammatory process. She was found to have
      granulomatous herpes simplex encephalitis and had a low cytokine response to Toll
      like receptor 3 stimulation.

PMID- 21961550
TI  - Unusual mesencephalic developmental venous anomaly causing obstructive
      hydrocephalus due to aqueductal stenosis.
AB  - Developmental venous anomalies (DVAs) are benign vascular malformations that
      rarely become symptomatic. They are anatomical variations of the venous drainage
      system and most are incidentally discovered. Mechanical (obstruction and
      compression of cerebral and neural structures) and flow-related pathological
      mechanisms have been described in rare cases of symptomatic DVAs. The authors
      present the case of a 10-month-old boy with a mesencephalic DVA compressing the
      aqueduct and causing occlusive hydrocephalus. Endoscopic inspection confirmed the
      venous malformation causing aqueductal stenosis. The authors successfully
      performed endoscopic third ventriculostomy, resulting in decrease in the size of
      the ventricles. At the 6-month follow-up after surgery, the patient had
      significantly progressed in his psychomotor development. One year postsurgery the
      patient is doing fine, with no neurological or developmental deficits.

PMID- 21961551
TI  - Prenatal molecular diagnosis of a severe type of L1 syndrome (X-linked
      hydrocephalus).
AB  - OBJECT: The aim of this study was to evaluate the feasibility of prenatal L1CAM
      gene testing for X-linked hydrocephalus (XLH). METHODS: In a nationwide study
      conducted in Japan between 1999 and 2009, the authors identified 51 different
      L1CAM gene mutations in 56 families with XLH. Of these 56 families, 9 obligate
      carriers requested prenatal gene mutation analysis for the fetal L1CAM gene in 14
      pregnancies. RESULTS: In 2004, new clinical guidelines for genetic testing were
      established by 10 Japanese genetic medicine-related societies. These guidelines
      stated that the genetic testing of carriers should be done only with their
      consent and with genetic counseling. Therefore, because females are carriers,
      since 2004, L1CAM gene analysis has not been performed for female fetuses. The
      authors report on 7 fetal genetic analyses that were performed at the request of
      families carrying L1CAM mutations, involving 3 female (prior to 2004) and 4 male
      fetuses. Of the 7 fetuses, 3 (1 male and 2 female) carried L1CAM mutations. Of
      these 3, 1 pregnancy (the male fetus) was terminated; in the other cases, the
      pregnancies continued, and 3 female and 3 male babies without the XLH phenotype
      were born. CONCLUSIONS: Prenatal L1CAM gene testing combined with genetic
      counseling was beneficial for families carrying L1CAM mutations.

PMID- 21961552
TI  - Hypodensity of extradural hematomas in children: an ominous sign.
AB  - OBJECT: The aim of this study was to analyze the correlation of hypodensity in
      extradural hematomas on CT with the clinical profile in pediatric patients. This
      is the only study available in this age group. METHODS: This was a prospective
      study conducted over a period of 3 years in which all children 18 years old or
      younger with a diagnosis of cranial extradural hematoma were included. The
      patients were allocated to 2 groups: those with mixed-density clots (17 cases)
      and those with classically hyperdense clots (52 cases). A comparative analysis
      between the 2 groups was conducted. RESULTS: Patients with mixed-density clots
      presented earlier to the hospital, had poor Glasgow Coma Scale scores at
      admission, exhibited large clot volumes, had a high incidence of active bleeding
      at surgery, and had increased morbidity and mortality as compared with the
      patients with hyperdense extradural hematomas. CONCLUSIONS: Early recognition and
      rapid evacuation of the mixed-density clot with restoration of hemostasis may
      result in a decline in morbidity and death in children with this entity.

PMID- 21961553
TI  - Pineal cysts.

PMID- 21961554
TI  - Sequential cation exchange in nanocrystals: preservation of crystal phase and
      formation of metastable phases.
AB  - We demonstrate that it is possible to convert CdSe nanocrystals of a given size,
      shape (either spherical or rod shaped), and crystal structure (either hexagonal
      wurtzite, i.e., hexagonal close packed (hcp), or cubic sphalerite, i.e., face
      centered cubic (fcc)), into ZnSe nanocrystals that preserve all these
      characteristics of the starting particles (i.e., size, shape, and crystal
      structure), via a sequence of two cation exchange reactions, namely, Cd(2+)
      =>Cu(+) =>Zn(2+). When starting from hexagonal wurtzite CdSe nanocrystals, the
      exchange of Cd(2+) with Cu(+) yields Cu(2)Se nanocrystals in a metastable
      hexagonal phase, of which we could follow the transformation to the more stable
      fcc phase for a single nanorod, under the electron microscope. Remarkably, these
      metastable hcp Cu(2)Se nanocrystals can be converted in solution into ZnSe
      nanocrystals, which yields ZnSe nanocrystals in a pure hcp phase.

PMID- 21961559
TI  - A comparative study of the most effective amendment for Pb, Zn and Cd
      immobilization in contaminated soils.
AB  - The problem of an extensive contamination of soils with metals can be resolved
      using an in situ chemical immobilization technology. Five substances (natural
      zeolite, bog iron ore, "Polifoska 15" fertilizer, triple superphosphate,
      diammonium phosphate) were tested to determine their efficiency to immobilize Zn,
      Pb and Cd in smelter-contaminated soil in the Upper Silesia region. Soil samples
      were collected at three sites located in the vincity of a Pb-Zn smelter and a
      sludge landfill near the town of Bukowno. Effective reduction of leachable and
      fitoavailable Zn, Pb and Cd concentrations in soil was observed after addition of
      diammonium phosphate, "Polifoska 15" fertilizer and bog iron ore amendments.
      Additional test proved that immobilization effect gained by these amendments
      sustains at low-temperature conditions. It was noticed that phosphate addition
      resulted in lowering pH and mobilization of As(V) in soils. Good immobilization
      effectiveness and lack of major adverse effects of bog iron application suggest
      that this is the method of choice.

PMID- 21961558
TI  - Dendritic cell tumor in a salivary gland lymph node: a rare differential
      diagnosis of salivary gland neoplasms.
AB  - Dendritic cell tumors are extremely rare neoplasms arising from antigen
      presenting cells of the immune system. We report a case of a 69-year-old man with
      an unremarkable medical history who presented with a 2-months history of a
      gradually enlarging painless, firm, mobile, 2 * 2-cm swelling at the caudal pole
      of the left parotid gland without systemic symptoms. Histologically, the tumor
      consisted of a spindle cell proliferation in an intraparotideal lymph node. Based
      on the histopathologic, immunohistochemical and electron microscopic findings, a
      dendritic cell tumor, not otherwise specified (NOS) in an intraparotideal lymph
      node was diagnosed.The patient underwent complete tumor resection, and is
      currently free of disease, 2 years after surgery. These extremely rare tumors
      must be distinguished from other more common tumors in the salivary glands.
      Awareness that dendritic cell tumors may occur in this localization, careful
      histologic evaluation and ancillary immunohistochemical and electron
      microscopical analyses should allow for recognition of this entity.

PMID- 21961560
TI  - Queen dominance and worker policing control reproduction in a threatened ant.
AB  - BACKGROUND: Efficient division of reproductive labor is a crucial characteristic
      of social insects and underlies their ecological and evolutionary success.
      Despite of the harmonious appearance of insect societies, nestmates may have
      different interests concerning the partitioning of reproduction among group
      members. This may lead to conflict about reproductive rights. As yet, few studies
      have investigated the allocation of reproduction among queens in multi - queen
      societies ("reproductive skew"). In the ant Leptothorax acervorum, reproductive
      skew varies considerably among populations. While reproduction is quite equally
      shared among nestmate queens in most populations from boreal Eurasia (low skew),
      colonies from populations at the edge of the species' range are characterized by
      "functional monogyny," i.e., high skew. The proximate mechanisms underlying high
      skew, in particular how workers influence which queen lays eggs, are not well
      understood. We investigated the behavior of queens and workers in functionally
      monogynous colonies of L. acervorum from two mountain ranges in central Spain.
      RESULTS: We provide evidence for both queen and worker influence on the outcome
      of conflict over reproduction in colonies of L. acervorum from Spain. The
      patterns of queen - queen aggression and worker - queen grooming and feeding
      after hibernation allowed predicting, which queen later began to lay eggs. In
      contrast, worker aggression towards queens was not clearly associated with a
      queen's future reproductive success. Queen - queen and worker - queen aggression
      differed in quality: queens typically engaged in ritualized dominance behavior,
      such as antennal boxing, while workers also attacked queens by biting and
      prolonged pulling on their legs and antennae. In several cases, overt worker
      aggression led to the expulsion of queens from the nest or their death.
      CONCLUSION: We conclude that queens of L. acervorum from Spain establish rank
      orders by ritualized dominance interactions, such as antennal boxing. Workers may
      reinforce these hierarchies by preferentially feeding and grooming high ranking
      queens and attacking lower ranking queens. Aggressive worker policing may thus
      stabilize functional monogyny. Optimal skew models predict that high skew in ants
      is associated with high dispersal costs. In central Spain, L. acervorum is
      restricted to small patches at higher elevations, which presumably makes
      dispersal and colony founding difficult. Because of the ecological requirements
      of L. acervorum and the predicted large impact of global change on central Spain,
      the functionally monogynous populations of this ant must be considered as
      threatened.

PMID- 21961561
TI  - Metabolism of calycosin, an isoflavone from Astragali Radix, in zebrafish larvae.
AB  - Although zebrafish has become a popular animal model for drug discovery and
      screening, drug metabolism in zebrafish remains largely unknown. In this study,
      we probed the metabolic capability of zebrafish larvae with calycosin, one of the
      major isoflavone constituents of Radix Astragali that was previously demonstrated
      to be angiogenic in the zebrafish model. The metabolism of calycosin and
      accumulation of its metabolites in zebrafish larvae were determined using an LC
      MS/MS method. Calycosin showed a slow but steady decrease from the culture medium
      as well as a steady accumulation in zebrafish larvae. Calycosin underwent major
      conjugation and minor oxidation in zebrafish larvae. A total of ten calycosin
      metabolites formed from glucuronidation, glucosylation, sulfation, oxidation or a
      combination of two of these metabolisms were identified, most of which were
      reported for the first time. Most metabolites increased steadily in the larvae
      over 24-h experimental period. The dominant phase II conjugation of calycosin in
      zebrafish larvae matched well with existing knowledge of isoflavone metabolism in
      mammalians. The findings shed a light in certain degree of similarity of phase II
      drug metabolism between zebrafish larvae and mammals and warrant further
      investigation on feasibility of adopting the zebrafish larvae as a whole-organism
      model for examining drug metabolism.

PMID- 21961562
TI  - Single wall carbon nanotubes enter cells by endocytosis and not membrane
      penetration.
AB  - BACKGROUND: Carbon nanotubes are increasingly being tested for use in cellular
      applications. Determining the mode of entry is essential to control and regulate
      specific interactions with cells, to understand toxicological effects of
      nanotubes, and to develop nanotube-based cellular technologies. We investigated
      cellular uptake of Pluronic copolymer-stabilized, purified ~145 nm long single
      wall carbon nanotubes (SWCNTs) through a series of complementary cellular, cell
      mimetic, and in vitro model membrane experiments. RESULTS: SWCNTs localized
      within fluorescently labeled endosomes, and confocal Raman spectroscopy showed a
      dramatic reduction in SWCNT uptake into cells at 4 degrees C compared with 37
      degrees C. These data suggest energy-dependent endocytosis, as shown previously.
      We also examined the possibility for non-specific physical penetration of SWCNTs
      through the plasma membrane. Electrochemical impedance spectroscopy and Langmuir
      monolayer film balance measurements showed that Pluronic-stabilized SWCNTs
      associated with membranes but did not possess sufficient insertion energy to
      penetrate through the membrane. SWCNTs associated with vesicles made from plasma
      membranes but did not rupture the vesicles. CONCLUSIONS: These measurements,
      combined, demonstrate that Pluronic-stabilized SWCNTs only enter cells via energy
      dependent endocytosis, and association of SWCNTs to membrane likely increases
      uptake.

PMID- 21961563
TI  - A retrospective cohort study of the potency of lipid-lowering therapy and race
      gender differences in LDL cholesterol control.
AB  - BACKGROUND: Reasons for race and gender differences in controlling elevated low
      density lipoprotein (LDL) cholesterol may be related to variations in prescribed
      lipid-lowering therapy. We examined the effect of lipid-lowering drug treatment
      and potency on time until LDL control for black and white women and men with a
      baseline elevated LDL. METHODS: We studied 3,484 older hypertensive patients with
      dyslipidemia in 6 primary care practices over a 4-year timeframe. Potency of
      lipid-lowering drugs calculated for each treated day and summed to assess total
      potency for at least 6 and up to 24 months. Cox models of time to LDL control
      within two years and logistic regression models of control within 6 months by
      race-gender adjust for: demographics, clinical, health care delivery,
      primary/specialty care, LDL measurement, and drug potency. RESULTS: Time to LDL
      control decreased as lipid-lowering drug potency increased (P < 0.001). Black
      women (N = 1,440) received the highest potency therapy (P < 0.001) yet were less
      likely to achieve LDL control than white men (N = 717) (fully adjusted hazard
      ratio [HR] 0.66 [95% CI 0.56-0.78]). Black men (N = 666) and white women (N =
      661) also had lower adjusted HRs of LDL control (0.82 [95% CI 0.69, 0.98] and
      0.75 [95% CI 0.64-0.88], respectively) than white men. Logistic regression models
      of LDL control by 6 months and other sensitivity models affirmed these results.
      CONCLUSIONS: Black women and, to a lesser extent, black men and white women were
      less likely to achieve LDL control than white men after accounting for lipid
      lowering drug potency as well as diverse patient and provider factors. Future
      work should focus on the contributions of medication adherence and response to
      treatment to these clinically important differences.

PMID- 21961564
TI  - Aerobic and anaerobic nonmicrobial methane emissions from plant material.
AB  - Methane (CH(4)) may be generated via microbial and nonmicrobial mechanisms.
      Nonmicrobial CH(4) is also ubiquitous in nature, such as in biomass burning, the
      Earth's crust, plants, and animals. Relative to microbial CH(4), nonmicrobial
      CH(4) is less understood. Using fresh (living) and dried (dead) leaves and
      commercial structural compounds (dead) of plants, a series of laboratory
      experiments have been conducted to investigate CH(4) emissions under aerobic and
      anaerobic conditions. CH(4) emissions from fresh leaves incubated at ambient
      temperatures were nonmicrobial and enhanced by anaerobic conditions. CH(4)
      emissions from dried leaves incubated at rising temperature ruled out a microbial
      mediated formation pathway and were plant-species-dependent with three categories
      of response to oxygen levels: enhanced by aerobic conditions, similar under
      aerobic and anaerobic conditions, and enhanced by anaerobic conditions. CH(4)
      emissions in plant structural compounds may help to fully understand nonmicrobial
      CH(4) formation in plant leaves. Experiments of reactive oxygen species (ROS)
      generator and scavengers indicate that ROS had a significant role in nonmicrobial
      CH(4) formation in plant material under aerobic and anaerobic conditions.
      However, the detailed mechanisms of the ROS were uncertain.

PMID- 21961565
TI  - Conformational flexibility in the allosteric regulation of human UDP-alpha-D
      glucose 6-dehydrogenase.
AB  - UDP-alpha-D-xylose (UDX) acts as a feedback inhibitor of human UDP-alpha-D
      glucose 6-dehydrogenase (hUGDH) by activating an unusual allosteric switch, the
      Thr131 loop. UDX binding induces the Thr131 loop to translate ~5 A through the
      protein core, changing packing interactions and rotating a helix (alpha6(136
      144)) to favor the formation of an inactive hexameric complex. But how does to
      conformational change occur given the steric packing constraints of the protein
      core? To answer this question, we deleted Val132 from the Thr131 loop to
      approximate an intermediate state in the allosteric transition. The 2.3 A
      resolution crystal structure of the deletion construct (Delta132) reveals an open
      conformation that relaxes steric constraints and facilitates repacking of the
      protein core. Sedimentation velocity studies show that the open conformation
      stabilizes the Delta132 construct as a hexamer with point group symmetry 32,
      similar to that of the active complex. In contrast, the UDX-inhibited enzyme
      forms a lower-symmetry, horseshoe-shaped hexameric complex. We show that the
      Delta132 and UDX-inhibited structures have similar hexamer-building interfaces,
      suggesting that the hinge-bending motion represents a path for the allosteric
      transition between the different hexameric states. On the basis of (i) main chain
      flexibility and (ii) a model of the conformational change, we propose that hinge
      bending can occur as a concerted motion between adjacent subunits in the high
      symmetry hexamer. We combine these results in a structurally detailed model for
      allosteric feedback inhibition and substrate--product exchange during the
      catalytic cycle.

PMID- 21961566
TI  - Purification and characterization of novel fibrinolytic proteases as potential
      antithrombotic agents from earthworm Perionyx excavatus.
AB  - Six protease fractions, namely FI, FII, FIII-1, FIII-2, FIII-3 and FIV, were
      isolated from Perionyx excavatus earthworm biomass by acetone precipitation,
      followed by serial chromatography using anion exchange, hydrophobic interaction
      and size exclusion chromatography. All fractions exhibited strong hydrolytic
      activity towards casein. The activity of six fractions towards fibrin, determined
      by fibrin plate assay, ranged from 44 to 831 plasmin unit.mg-1 and ranked as FIII
      3 > FIII-2 > FI > FIII-1 > FIV > FII. Casein degradation was optimal at pH 7 and
      11, and at 45-60 degrees C. All fractions were considerably stable at high
      temperature and wide pH range. They were completely inhibited by
      phenylmethylsulfonyl fluoride (PMSF). The molecular weights (MW) and isoelectric
      points (pI) determined by 2D-electrophoresis were 27.5-34.5 kDa, and 4.3-5.2,
      respectively. Tandem mass spectrometry (MS) analysis was used to deduce the amino
      acid sequences of some peptides from FIII-1 and FIII-2. The sequences shared
      16.9% and 13.2% similarity, respectively, with the fibrinolytic enzymes from two
      related earthworm species, Lumbricus rubellus and Eisenia fetida. The P.
      excavatus proteases were classified as serine proteases. They could perform rapid
      hydrolysis on both coagulated fibrous fibrin and soluble fibrinogen monomers
      without the presence of activators such as tPA or urokinase.

PMID- 21961567
TI  - Exploring the sources of 'missingness' in brain tissue monitoring datasets: an
      observational cohort study.
AB  - OBJECTIVE: To investigate the frequency/category of missing electronic data in
      export files from patients admitted to the intensive care unit (ICU) with severe
      traumatic brain injury (TBI). RESEARCH DESIGN: Observational cohort study.
      METHODOLOGY: Patient data-streams for brain temperature (T(br)) and intracranial
      pressure (ICP) were analysed. Missing data was classified as: missing completely
      at random (MCAR), missing at random (MAR), missing not at random (MNAR). RESULTS:
      Sixty-two patients were studied; 60% of missing T(br) and ICP data events were
      attributed to electronic data acquisition 'faults'. Missing data rate ranged from
      9-43% (median 25%). Cross-reference of missing data to clinical observation
      sheets and medical case notes shows that disconnection of sensors from monitors
      during critical events are common. Conclusions and implications for further
      research: Of concern for clinical management of patients with TBI is the
      detection of sudden changes in ICP or brain temperature; the parameters which
      forewarn of impending intracranial catastrophes. Missing data occurred at
      critical times of the patients stay in the ICU. This work should alert research
      clinicians of the need to scrutinize monitored physiological data to establish
      the percentage of missing values in order to obviate bias in the interpretation
      of results.

PMID- 21961568
TI  - Friendship, loneliness and psychosocial functioning in children with traumatic
      brain injury.
AB  - OBJECTIVE: This study compares friendship quality, rates of loneliness and
      general psychosocial functioning in children who have sustained a traumatic brain
      injury (TBI) with non-injured controls. METHODS: A between-subjects design with
      14 participants in the TBI group and 14 in the non-injured control group, aged
      between 7-13 years and matched for age, gender, receptive vocabulary and socio
      economic status. Children completed measures of receptive vocabulary (BPVS II),
      friendship quality (FQQ-R) and loneliness (LSDS). The main caregiver was asked to
      assess social skills and social withdrawal (PIC-2) and general psychosocial and
      behavioural functioning (SDQ). RESULTS: Significant differences were not found on
      measures completed by children or on the PIC-2. On the SDQ, total difficulties
      were rated as much greater by caregivers in the TBI group (z = -2.6, p = 0.009)
      and these were mainly associated with sub-scales relating to emotional problems
      and hyperactivity. CONCLUSIONS: Whilst evidence for friendship problems was not
      found in children with TBI, evidence for emotional and behavioural difficulties
      that may lead to social vulnerabilities later in life were found. This indicates
      a need for prospective longitudinal research to explore the complex relationship
      between TBI and poorer social outcomes that may not become evident until
      adolescence.

PMID- 21961569
TI  - Impact of post-traumatic hypersomnia on functional recovery of cognition and
      communication.
AB  - PRIMARY OBJECTIVE: To assess aspects of cognition and communication, in response
      to the treatment of post-traumatic hypersomnia and mood disturbance. RESEARCH
      DESIGN: A single case study; pre-post intervention. METHODS AND PROCEDURES: The
      participant was a male with severe TBI and cognitive-communication impairments,
      who subsequently developed sleep and mood disturbance and excessive daytime
      sleepiness. The Daily Cognitive-Communication and Sleep Profile (D-CCASP),
      Clinical Interview, Epworth and Stanford Sleepiness Scales and polysomnography
      assessed sleep and wakefulness. Cognitive-communication was also assessed by the
      D-CCASP. His sleep, wake and mood difficulties were pharmacologically managed.
      MAIN OUTCOMES AND RESULTS: Baseline polysomnography indicated abnormal sleep.
      There was a clear positive relationship between quality of sleep, language
      processing, attention and memory, seen across the phases of the medication
      intervention (p < 0.01). CONCLUSIONS: A comprehensive pharmacological management
      programme addressing the multi-factorial underlying aetiology was successful in
      improving sleep, arousal and mood. The D-CCASP was found to be clinically and
      statistically sensitive to reported changes in cognitive-communication function
      in relation to improvements in sleep and daytime arousal. These findings suggest
      that management of sleep/wake disturbances and mood post-traumatic brain injury
      can potentially facilitate improvements in cognitive-communication function which
      may, in turn, facilitate participation in rehabilitation and community
      integration.

PMID- 21961571
TI  - Community integration following TBI: an examination of community integration
      measures within the ICF framework.
AB  - PURPOSE: The objectives of the present study are (1) to examine whether the
      content of existing community integration measures used following traumatic brain
      injury (TBI) is represented in the International Classification of Functioning,
      Disability and Health (ICF) and (2) to determine if the ICF provides a reasonable
      framework within which such measurement tools may be compared. METHOD: Five
      commonly-used assessment instruments were selected for inclusion. Independent
      raters mapped identified measurement concepts to the ICF using established
      linking rules. RESULTS: One hundred and eighty-five concepts were identified from
      85 items in five scales. Of these more than 75% could be linked to the ICF. The
      majority of linked concepts were assigned to 64 categories within the activities
      and participation component of the ICF; however, the focus of assessment within
      each instrument varied considerably. CONCLUSION: Through a standardized process
      of item mapping to the ICF, one may examine operationalizations of community
      integration. This may help inform selection of a method of assessment appropriate
      to both the subject population and clinical or research purpose. However, this
      process allows comparison of only the objective content of measurement tools.
      Subjective evaluations may also be necessary to provide comprehensive assessment
      of community integration.

PMID- 21961570
TI  - Health-related quality-of-life and behavioural outcome in survivors of childhood
      meningitis.
AB  - OBJECTIVE: To describe behavioural and health-related quality-of-life (HRQoL)
      outcomes in survivors of childhood meningitis and identify variables predictive
      of psychosocial outcome. METHODS: Psychosocial outcomes were measured via parent
      and teacher report using the Strengths and Difficulties Questionnaire (SDQ) and
      the Paediatric Quality of Life Inventory (PedsQL Core & Fatigue versions).
      Participants were 346[corrected] consecutive survivors admitted to a regional
      children's hospital (1991-2007). One hundred and twelve of 346 (32%) [corrected]
      returned postal questionnaires and file review confirmed diagnosis in 100 cases.
      RESULTS: At a mean of 8 years post-illness 32% of parents and 19% of teachers
      reported clinically significant behavioural difficulties on the SDQ; along with
      significantly lowered HRQoL on PedsQL measures. Later sequelae such as learning
      disability and hearing/visual impairment, along with socioeconomic status,
      independently predicted behavioural and HRQoL outcome on regression analysis.
      Acute disease complications were associated with later occurrence of epilepsy,
      learning disability and visual impairment, but not directly with psychosocial
      outcomes at time of follow-up. CONCLUSIONS: Survivors with these sequelae should
      be screened for emotional and behavioural difficulties during key developmental
      transitions such as school entry. These findings strongly support recent UK
      clinical guidelines (NICE and SIGN) proposing that parents be made aware of
      possible psychological complications on discharge.

PMID- 21961572
TI  - Participation outcomes for children with acquired brain injury: a narrative
      review.
AB  - AIM: To review the literature on participation outcomes used in children and
      adolescents with acquired brain injury (ABI) and to synthesize the available
      evidence on recovery trajectories in participation after ABI. METHOD: This study
      searched electronic databases (Medline, Cinahl, Embase and PsychInfo) from March
      2011 back to the earliest available time (1966) using the following terms with
      brain injury (brain tumours excluded) and children: social or community or school
      and outcome assessment or participation. Retrieved articles were rated for
      methodological quality using Oxford Centre for Evidence Based Medicine criteria
      (CEBM). RESULTS: Sixteen articles were included for analysis. The methodological
      characteristics and quality of these studies varied considerably. Three studies
      used an explicit participation measure, nine studies featured an implicit
      participation measure and four used tailored participation measures. There is
      level 1c evidence that children and adolescents with ABI have participation
      restrictions at home, at school and in the community 18 months (SD = 14) after
      discharge. CONCLUSIONS: The available literature indicates that children and
      adolescents with ABI are at risk for participation restrictions. Research on
      recovery trajectories in participation after ABI in children is lacking.
      Longitudinal studies using explicit participation measures and higher quality
      research methodologies (quantitative, qualitative and mixed methods) are
      recommended.

PMID- 21961573
TI  - Early use of Xeomin neurotoxin for local anti-spasticity therapy for pes equines
      after acquired brain injury (ABI).
AB  - PRIMARY OBJECTIVE: The acute management of spasticity following ABI is
      challenging. Contractures can occur during the acute phases of illness. The
      joints most affected are the shoulders and the ankles. RESEARCH DESIGN: A case
      study of a 48-year-old female patient who received local chemoneurolytic anti
      spasticity therapy following a severe subarachnoid haemorrhage for pes equines
      deformity is presented to illustrate the role of focal neurotoxin therapy.
      METHODS AND PROCEDURES: The increasing spasticity in her legs was observed and
      could not be effectively treated with oral anti-spasticity agents or intensive
      physiotherapy. As spasticity increased (Modified Ashworth Scale 4), mobility of
      the right foot continued to deteriorate, leading to indication for local anti
      spasticity treatment with Xeomin neurotoxin. The spastic pes equinus was injected
      with Xeomin(r) using a total dose of 150 U. MAIN OUTCOMES AND RESULTS: On the 6th
      day after injection, a gradual reduction in spasticity was observed in the
      injected muscle (Modified Ashworth Scale 1-2) and an increasing improvement in
      joint mobility. CONCLUSIONS: Early local anti-spasticity treatment with Xeomin is
      effective treatment. The cost of the intervention would appear to be high, but if
      one compares it with the costs of conservative treatment, it is not more
      expensive.

PMID- 21961574
TI  - Familiarity and prevalence of Facebook use for social networking among
      individuals with traumatic brain injury.
AB  - OBJECTIVE: To examine use of Facebook among individuals with traumatic brain
      injury (TBI) and to identify barriers preventing Facebook use. METHOD: An online
      survey was developed assessing frequency and barriers to use of Facebook. The
      survey was distributed electronically to individuals with TBI through four state
      brain injury associations. Ninety-six individuals with TBI completed the survey
      (60% female, age range: 23-70). RESULTS: The relative majority of respondents
      (60%) reported using Facebook on a regular basis. Among those who reported not
      using Facebook, the most commonly reported barriers were security concerns and
      cognitive deficits. Approximately half of non-users indicated interest in
      learning to use the site, with 70% reporting that they would use it more if they
      were more knowledgeable about it. Both users and non-users indicated that they
      would be interested in receiving training to learn how to use Facebook better.
      CONCLUSIONS: Social networking sites are increasingly important in creating and
      maintaining social networks. A significant number of survey respondents expressed
      interest in further training on Facebook use. Increased use of social networking
      may have important implications for social integration among individuals with
      TBI.

PMID- 21961575
TI  - A speech expression disorder in patients with severe diffuse brain injury who
      emerged from a vegetative or minimally conscious state.
AB  - OBJECTIVE: The purpose of this study was to highlight a speech expression
      disorder considered as a mixed speech apraxia (SA) and dysarthria syndrome in
      patients with chronic severe diffuse brain injury (DBI) and to determine its
      correlation with anatomical localizations of brain lesions using neuroimaging.
      METHODS: Among 140 patients with chronic severe DBI, eight showed this type of
      speech disorder. MRI (five patients) and FDG-PET (six patients) procedures were
      performed. RESULTS: Affected patients could comprehend verbally, read words
      silently and express words using a word board. Compared with SA, the disorder is
      characterized by similarities in regards to reduced phonation and marked facio
      oral apraxia, but by distinct differences in terms of an accompanying dysphagia
      and pyramidal/extra-pyramidal symptoms that are similar to symptoms associated
      with dysarthria due to pseudobulbar palsy. Diffuse regions of the white matter
      including the left arcuate fasciculus (AF) were significantly decreased in
      fractional anisotropy value. However, there was no significant cortical metabolic
      damage in FDG-PET. CONCLUSIONS: The observed speech disorder in these patients is
      a characteristic entity related to dysfunction of speech expression and may be
      attributable to damage of not only the AF but also a number of fibres that are
      related to dysarthria, cognitive and emotional impairments and pyramidal/extra
      pyramidal symptoms.

PMID- 21961576
TI  - The evolving experience with therapeutic TNF inhibition in sepsis: considering
      the potential influence of risk of death.
AB  - INTRODUCTION: Septic shock is highly lethal and its incidence is increasing.
      Although TNF-alpha plays a key role in sepsis pathogenesis, past efforts to
      therapeutically inhibit it had limited success. However, there is continued
      interest in such therapies and there are now ongoing Phase II sepsis trials
      testing the effects of AZD9773, a TNF-directed polyclonal antibody fragment
      preparation. Experience with anti-inflammatory agents suggested that their
      efficacy may relate to sepsis-associated risk of death. AREAS COVERED: An
      overview of the biology of TNF and experimental data implicating TNF as a key
      mediator in sepsis pathogenesis; a review of the earlier clinical experience with
      anti-TNF therapies demonstrating that when examined across 12 trials, these
      agents had a highly consistent overall effect which although not reaching
      significance, was on the side of benefit; a review of data showing that sepsis
      associated risk of death may influence the efficacy of anti-inflammatory agents
      like anti-TNF ones and a review of the rational and clinical experience to date
      with AZD9773 and its precursor, CytoFab. EXPERT OPINION: Discusses variables that
      may need to be accounted for to maximize the success of clinical trials in sepsis
      testing agents that modulate host inflammation.

PMID- 21961577
TI  - A randomized controlled trial to investigate the influence of low dose
      radiotherapy on immune stimulatory effects in liver metastases of colorectal
      cancer.
AB  - BACKGROUND: Insufficient migration and activation of tumor specific effector T
      cells in the tumor is one of the main reasons for inadequate host anti-tumor
      immune response. External radiation seems to induce inflammation and activate the
      immune response. This phase I/II clinical trial aims to evaluate whether low dose
      single fraction radiotherapy can improve T cell associated antitumor immune
      response in patients with colorectal liver metastases. METHODS/DESIGN: This is an
      investigator-initiated, prospective randomised, 4-armed, controlled Phase I/II
      trial. Patients undergoing elective hepatic resection due to colorectal cancer
      liver metastasis will be enrolled in the study. Patients will receive 0 Gy, 0.5
      Gy, 2 Gy or 5 Gy radiation targeted to their liver metastasis. Radiation will be
      applied by external beam radiotherapy using a 6 MV linear accelerator (Linac)
      with intensity modulated radiotherapy (IMRT) technique two days prior to surgical
      resection. All patients admitted to the Department of General-, Visceral-, and
      Transplantion Surgery, University of Heidelberg for elective hepatic resection
      are consecutively screened for eligibility into this trial, and written informed
      consent is obtained before inclusion. The primary objective is to assess the
      effect of active local external beam radiation dose on, tumor infiltrating T
      cells as a surrogate parameter for antitumor activity. Secondary objectives
      include radiogenic treatment toxicity, postoperative morbidity and mortality,
      local tumor control and recurrence patterns, survival and quality of life.
      Furthermore, frequencies of systemic tumor reactive T cells in blood and bone
      marrow will be correlated with clinical outcome. DISCUSSION: This is a randomized
      controlled patient blinded trial to assess the safety and efficiency of low dose
      radiotherapy on metastasis infiltrating T cells and thus potentially enhance the
      antitumor immune response. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01191632.

PMID- 21961578
TI  - Brain metastasis of Wilms tumor with diffuse anaplasia and complex cytogenetic
      phenotype in a child with neurofibromatosis Type 1.
AB  - The authors report the first case of a Wilms tumor (WT) with diffuse anaplasia
      metastatic to the brain in a 13-year-old girl with a history of neurofibromatosis
      Type 1. At presentation, the metastatic tumor had radiological features that
      suggested a meningioma. Histologically it was characterized by striking anaplasia
      and features similar to the patient's previously resected WT with diffuse
      anaplasia.

PMID- 21961579
TI  - Magic angle spinning NMR-based metabolic profiling of head and neck squamous cell
      carcinoma tissues.
AB  - High-resolution magic-angle spinning (HR-MAS) proton NMR spectroscopy is used to
      explore the metabolic signatures of head and neck squamous cell carcinoma (HNSCC)
      which included matched normal adjacent tissue (NAT) and tumor originating from
      tongue, lip, larynx and oral cavity, and associated lymph-node metastatic (LN
      Met) tissues. A total of 43 tissues (18 NAT, 18 Tumor and 7 LN-Met) from 22 HNSCC
      patients were analyzed. Principal Component Analysis of NMR data showed a clear
      classification between NAT and tumor tissues, however, LN-Met tissues were
      classified among tumor. A partial least-squares discriminant analysis model
      generated from NMR metabolic profiles was used to differentiate normal from tumor
      samples (Q(2) > 0.80, Receiver Operator Characteristic area under the curve
      >0.86, using 7-fold cross validation). HNSCC and LN-Met tissues showed elevated
      levels of lactate, amino acids including leucine, isoleucine, valine, alanine,
      glutamine, glutamate, aspartate, glycine, phenylalanine and tyrosine, choline
      containing compounds, creatine, taurine, glutathione, and decreased levels of
      triglycerides. These elevated metabolites were associated with highly active
      glycolysis, increased amino acids influx (anaplerosis) into the TCA cycle,
      altered energy metabolism, membrane choline phospholipid metabolism, and
      oxidative and osmotic defense mechanisms. Moreover, decreased levels of
      triglycerides may indicate lipolysis followed by beta-oxidation of fatty acids
      that may exist to deliver bioenergy for rapid tumor cell proliferation and
      growth.

PMID- 21961580
TI  - [4 + 2] Cyclocondensation reactions of tungsten-dihydropyridine complexes and the
      generation of tri- and tetrasubstituted piperidines.
AB  - A new method for the preparation of functionalized piperidines is described in
      which various dihydropyridine (DHP) complexes of {TpW(NO)(PMe(3))} that are
      derived from pyridine-borane undergo [4 + 2] cyclocondensation with enones,
      enals, nitrosobenzene, and several isocyanates to form [2.2.2] bicyclic species.
      In several cases the diazabicyclooctene products derived from DHP complexes and
      isocyanates can be further elaborated into novel syn-2,5-disubstituted and 2,3,6
      trisubstituted piperidinamides.

PMID- 21961581
TI  - A dynamic model of transcriptional imprinting derived from the vitellogenesis
      memory effect.
AB  - Transcriptional memory of transient signals can be imprinted on living systems
      and influence their reactivity to repeated stimulations. Although they are
      classically ascribed to structural chromatin rearrangements in eukaryotes, such
      behaviors can also rely on dynamic memory circuits with sustained self
      amplification loops. However, these phenomena are either of finite duration, or
      conversely associated to sustained phenotypic changes. A mechanism is proposed,
      in which only the responsiveness of the target gene is durably reset at a higher
      level after primary stimulation, using the celebrated but still puzzling
      vitellogenesis memory effect. The basic ingredients of this system are: 1), a
      positive autoregulation of the estrogen receptor alpha gene; 2), a strongly
      cooperative action of the estradiol receptor on vitellogenin expression; and 3),
      a variant isoform of the estradiol receptor with two autonomous transcription
      activating modules, one of which is signal-independent and the other, signal
      dependent. Realistic quantification supports the possibility of a multistationary
      situation in which ligand-independent activity is unable by itself to prime the
      amplification loop, but can click the system over a memory threshold after a
      primary stimulation. This ratchet transcriptional mechanism can have
      developmental and ecotoxicological importance and explain lifelong imprinting of
      past exposures without apparent phenotypic changes before restimulation and
      without need for persistent chromatin modifications.

PMID- 21961582
TI  - Physical limits on cooperative protein-DNA binding and the kinetics of
      combinatorial transcription regulation.
AB  - Much of the complexity observed in gene regulation originates from cooperative
      protein-DNA binding. Although studies of the target search of proteins for their
      specific binding sites on the DNA have revealed design principles for the
      quantitative characteristics of protein-DNA interactions, no such principles are
      known for the cooperative interactions between DNA-binding proteins. We consider
      a simple theoretical model for two interacting transcription factor (TF) species,
      searching for and binding to two adjacent target sites hidden in the genomic
      background. We study the kinetic competition of a dimer search pathway and a
      monomer search pathway, as well as the steady-state regulation function mediated
      by the two TFs over a broad range of TF-TF interaction strengths. Using a
      transcriptional AND-logic as exemplary functional context, we identify the
      functionally desirable regime for the interaction. We find that both weak and
      very strong TF-TF interactions are favorable, albeit with different
      characteristics. However, there is also an unfavorable regime of intermediate
      interactions where the genetic response is prohibitively slow.

PMID- 21961583
TI  - Measurements of the acidification kinetics of single SynaptopHluorin vesicles.
AB  - Uptake of neurotransmitters into synaptic vesicles is driven by the proton
      gradient established across the vesicle membrane. The acidification of synaptic
      vesicles, therefore, is a crucial component of vesicle function. Here we present
      measurements of acidification rate constants from isolated, single synaptic
      vesicles. Vesicles were purified from mice expressing a fusion protein termed
      SynaptopHluorin created by the fusion of VAMP/synaptobrevin to the pH-sensitive
      super-ecliptic green fluorescent protein. We calibrated SynaptopHluorin
      fluorescence to determine the relationship between fluorescence intensity and
      internal vesicle pH, and used these values to measure the rate constant of
      vesicle acidification. We also measured the effects of ATP, glutamate, and
      chloride on acidification. We report acidification time constants of 500 ms to 1
      s. The rate of acidification increased with increasing extravesicular
      concentrations of ATP and glutamate. These data provide an upper and a lower
      bound for vesicle acidification and indicate that vesicle readiness can be
      regulated by changes in energy and transmitter availability.

PMID- 21961584
TI  - Integrating multiple signals into cell decisions by networks of protein
      modification cycles.
AB  - Posttranslational protein modifications play a key role in regulating cellular
      processes. We present a general model of reversible protein modification networks
      and demonstrate that a single protein modified by several enzymes is capable of
      integrating multiple signals into robust digital decisions by switching between
      multiple forms that can activate distinct cellular processes. First we consider
      two competing protein modification cycles and show that in the saturated regime,
      the protein is concentrated into a single form determined by the enzyme
      activities. We generalize this to protein modification networks with tree
      structure controlled by multiple enzymes that can be characterized by their phase
      diagram, which is a partition of the space of enzyme activities into regions
      corresponding to different dominant forms. We show that the phase diagram can be
      obtained analytically from the wiring diagram of the modification network by
      recursively solving a set of balance equations for the steady-state distributions
      and then applying a positivity condition to determine the regions corresponding
      to different responses. We also implement this method in a computer algebra
      system that automatically generates the phase diagram as a set of inequalities.
      Based on this theoretical framework, we determine some general properties of
      protein modification systems.

PMID- 21961585
TI  - Dynamic role of cross-linking proteins in actin rheology.
AB  - We develop a computational model to compare the relative importance of unbinding
      and unfolding of actin cross-linking proteins (ACPs) in the dynamic properties of
      the actin cytoskeleton. We show that in the strain-stiffening regime with typical
      physiological and experimental strain rates, unbinding events are predominant
      with negligible unfolding. ACPs unbound by greater forces experience larger
      displacements, with a tendency to rebind to different filaments. At constant
      strain, stress relaxes to physiological levels by unbinding only--not unfolding-
      of ACPs, which is consistent with experiments. Also, rebinding of ACPs dampens
      full relaxation of stress. When the network is allowed to return to a stress-free
      state after shear deformation, plastic deformation is observed only with
      unbinding. These results suggest that despite the possibility of unfolding,
      unbinding of ACPs is the major determinant for the rheology of the actin network.

PMID- 21961586
TI  - Tank treading of optically trapped red blood cells in shear flow.
AB  - Tank-treading (TT) motion is established in optically trapped, live red blood
      cells (RBCs) held in shear flow and is systematically investigated under varying
      shear rates, temperature (affecting membrane viscosity), osmolarity (resulting in
      changes in RBC shape and cytoplasmic viscosity), and viscosity of the suspending
      medium. TT frequency is measured as a function of membrane and cytoplasmic
      viscosity, the former being four times more effective in altering TT frequency.
      TT frequency increases as membrane viscosity decreases, by as much as 10% over
      temperature changes of only 4 degrees C at a shear rate of ~43 s(-1). A threshold
      shear rate (1.5 +/- 0.3 s(-1)) is observed below which the TT frequency drops to
      zero. TT motion is also observed in shape-engineered (spherical) RBCs and those
      with cholesterol-depleted membranes. The TT threshold is less evident in both
      cases but the TT frequency increases in the latter cells. Our findings indicate
      that TT motion is pervasive even in folded and deformed erythrocytes, conditions
      that occur when such erythrocytes flow through narrow capillaries.

PMID- 21961587
TI  - Molecular mapping of general anesthetic sites in a voltage-gated ion channel.
AB  - Several voltage-gated ion channels are modulated by clinically relevant doses of
      general anesthetics. However, the structural basis of this modulation is not well
      understood. Previous work suggested that n-alcohols and inhaled anesthetics
      stabilize the closed state of the Shaw2 voltage-gated (Kv) channel (K-Shaw2) by
      directly interacting with a discrete channel site. We hypothesize that the
      inhibition of K-Shaw2 channels by general anesthetics is governed by interactions
      between binding and effector sites involving components of the channel's
      activation gate. To investigate this hypothesis, we applied Ala/Val scanning
      mutagenesis to the S4-S5 linker and the post-PVP S6 segment, and conducted
      electrophysiological analysis to evaluate the energetic impact of the mutations
      on the inhibition of the K-Shaw2 channel by 1-butanol and halothane. These
      analyses identified residues that determine an apparent binding cooperativity and
      residue pairs that act in concert to modulate gating upon anesthetic binding. In
      some instances, due to their critical location, key residues also influence
      channel gating. Complementing these results, molecular dynamics simulations and
      in silico docking experiments helped us visualize possible anesthetic sites and
      interactions. We conclude that the inhibition of K-Shaw2 by general anesthetics
      results from allosteric interactions between distinct but contiguous binding and
      effector sites involving inter- and intrasubunit interfaces.

PMID- 21961588
TI  - Gating at the selectivity filter of ion channels that conduct Na+ and K+ ions.
AB  - The NaK channel is a cation selective channel with similar permeability for K(+)
      and Na(+). The available crystallographic structure of wild-type (WT) NaK is
      usually associated with a conductive state of the channel. Here, potential of
      mean force for complete conduction events of Na(+) and K(+) ions through NaK show
      that: i), large energy barriers prevent the passage of ions through the WT NaK
      structure, ii), the barriers are correlated to the presence of a hydrogen bond
      between Asp-66 and Asn-68, and iii), the structure of NaK mutated to mimic cyclic
      nucleotide-gated channels conducts Na(+) and K(+). These results support the
      hypothesis that the filter of cation selective channels can adopt at least two
      different structures: a conductive one, represented by the x-ray structures of
      the NaK-CNG chimeras, and a closed one, represented by the x-ray structures of
      the WT NaK.

PMID- 21961589
TI  - Organization and dynamics of Fas transmembrane domain in raft membranes and
      modulation by ceramide.
AB  - To comprehend the molecular processes that lead to the Fas death receptor
      clustering in lipid rafts, a 21-mer peptide corresponding to its single
      transmembrane domain (TMD) was reconstituted into mammalian raft model membranes
      composed of an unsaturated glycerophospholipid, sphingomyelin, and cholesterol.
      The peptide membrane lateral organization and dynamics, and its influence on
      membrane properties, were studied by steady-state and time-resolved fluorescence
      techniques and by attenuated total reflection Fourier transformed infrared
      spectroscopy. Our results show that Fas TMD is preferentially localized in liquid
      disordered membrane regions and undergoes a strong reorganization as the membrane
      composition is changed toward the liquid-ordered phase. This results from the
      strong hydrophobic mismatch between the length of the peptide hydrophobic stretch
      and the hydrophobic thickness of liquid-ordered membranes. The stability of
      nonclustered Fas TMD in liquid-disordered domains suggests that its sequence may
      have a protective function against nonligand-induced Fas clustering in lipid
      rafts. It has been reported that ceramide induces Fas oligomerization in lipid
      rafts. Here, it is shown that neither Fas TMD membrane organization nor its
      conformation is affected by ceramide. These results are discussed within the
      framework of Fas membrane signaling events.

PMID- 21961590
TI  - Native ligands change integrin sequestering but not oligomerization in raft
      mimicking lipid mixtures.
AB  - Distinct lipid environments, including lipid rafts, are increasingly recognized
      as a crucial factor affecting membrane protein function in plasma membranes.
      Unfortunately, an understanding of their role in membrane protein activation and
      oligomerization has remained elusive due to the challenge of characterizing these
      often small and transient plasma membrane heterogeneities in live cells. To
      address this difficulty, we present an experimental model membrane platform based
      on polymer-supported lipid bilayers containing stable raft-mimicking domains
      (type I) and homogeneous cholesterol-lipid mixtures (type II) into which
      transmembrane proteins are incorporated (alpha(v)beta(3) and alpha(5)beta(1)
      integrins). These flexible lipid platforms enable the use of confocal
      fluorescence spectroscopy, including the photon counting histogram method, in
      tandem with epifluorescence microscopy to quantitatively probe the effect of the
      binding of native ligands from the extracellular matrix ligands (vitronectin and
      fibronectin for alpha(v)beta(3) and alpha(5)beta(1), respectively) on domain
      specific protein sequestration and on protein oligomerization state. We found
      that both alpha(v)beta(3) and alpha(5)beta(1) sequester preferentially to nonraft
      domains in the absence of extracellular matrix ligands, but upon ligand addition,
      alpha(v)beta(3) sequesters strongly into raft-like domains and alpha(5)beta(1)
      loses preference for either raft-like or nonraft-like domains. A corresponding
      photon counting histogram analysis showed that integrins exist predominantly in a
      monomeric state. No change was detected in oligomerization state upon ligand
      binding in either type I or type II bilayers, but a moderate increase in
      oligomerization state was observed for increasing concentrations of cholesterol.
      The combined findings suggest a mechanism in which changes in integrin
      sequestering are caused by ligand-induced changes in integrin conformation and/or
      dynamics that affect integrin-lipid interactions without altering the integrin
      oligomerization state.

PMID- 21961591
TI  - STED nanoscopy reveals molecular details of cholesterol- and cytoskeleton
      modulated lipid interactions in living cells.
AB  - Details about molecular membrane dynamics in living cells, such as lipid-protein
      interactions, are often hidden from the observer because of the limited spatial
      resolution of conventional far-field optical microscopy. The superior spatial
      resolution of stimulated emission depletion (STED) nanoscopy can provide new
      insights into this process. The application of fluorescence correlation
      spectroscopy (FCS) in focal spots continuously tuned down to 30 nm in diameter
      distinguishes between free and anomalous molecular diffusion due to, for example,
      transient binding of lipids to other membrane constituents, such as lipids and
      proteins. We compared STED-FCS data recorded on various fluorescent lipid analogs
      in the plasma membrane of living mammalian cells. Our results demonstrate details
      about the observed transient formation of molecular complexes. The diffusion
      characteristics of phosphoglycerolipids without hydroxyl-containing headgroups
      revealed weak interactions. The strongest interactions were observed with
      sphingolipid analogs, which showed cholesterol-assisted and cytoskeleton
      dependent binding. The hydroxyl-containing headgroup of gangliosides,
      galactosylceramide, and phosphoinositol assisted binding, but in a much less
      cholesterol- and cytoskeleton-dependent manner. The observed anomalous diffusion
      indicates lipid-specific transient hydrogen bonding to other membrane molecules,
      such as proteins, and points to a distinct connectivity of the various lipids to
      other membrane constituents. This strong interaction is different from that
      responsible for forming cholesterol-dependent, liquid-ordered domains in model
      membranes.

PMID- 21961592
TI  - Roles for cardiac MyBP-C in maintaining myofilament lattice rigidity and
      prolonging myosin cross-bridge lifetime.
AB  - We investigated the influence of cardiac myosin binding protein-C (cMyBP-C) and
      its constitutively unphosphorylated status on the radial and longitudinal
      stiffnesses of the myofilament lattice in chemically skinned myocardial strips of
      the following mouse models: nontransgenic (NTG), effective null for cMyBP-C
      (t/t), wild-type cMyBP-C expressed into t/t (WT(t/t)), and constitutively
      unphosphorylated cMyBP-C (AllP-(t/t)). We found that the absence of cMyBP-C in
      the t/t and the unphosphorylated cMyBP-C in the AllP-(t/t) resulted in a
      compressible cardiac myofilament lattice induced by rigor not observed in the NTG
      and WT(t/t). These results suggest that the presence and phosphorylation of the N
      terminus of cMyBP-C provides structural support and radial rigidity to the
      myofilament lattice. Examination of myofilament longitudinal stiffness under
      rigor conditions demonstrated a significant reduction in cross-bridge-dependent
      stiffness in the t/t compared with NTG controls, but not in the AllP-(t/t)
      compared with WT(t/t) controls. The absence of cMyBP-C in the t/t and the
      unphosphorylated cMyBP-C in the AllP-(t/t) both resulted in a shorter myosin
      cross-bridge lifetime when myosin isoform was controlled. These data collectively
      suggest that cMyBP-C provides radial rigidity to the myofilament lattice through
      the N-terminus, and that disruption of the phosphorylation of cMyBP-C is
      sufficient to abolish this structural role of the N-terminus and shorten cross
      bridge lifetime. Although the presence of cMyBP-C also provides longitudinal
      rigidity, phosphorylation of the N-terminus is not necessary to maintain
      longitudinal rigidity of the lattice, in contrast to radial rigidity.

PMID- 21961593
TI  - The effect of linker histone's nucleosome binding affinity on chromatin unfolding
      mechanisms.
AB  - Eukaryotic gene activation requires selective unfolding of the chromatin fiber to
      access the DNA for processes such as DNA transcription, replication, and repair.
      Mutation/modification experiments of linker histone (LH) H1 suggest the
      importance of dynamic mechanisms for LH binding/dissociation, but the effects on
      chromatin's unfolding pathway remain unclear. Here we investigate the stretching
      response of chromatin fibers by mesoscale modeling to complement single-molecule
      experiments, and present various unfolding mechanisms for fibers with different
      nucleosome repeat lengths (NRLs) with/without LH that are fixed to their cores or
      bind/unbind dynamically with different affinities. Fiber softening occurs for
      long compared to short NRL (due to facile stacking rearrangements), dynamic
      compared to static LH/core binding as well as slow rather than fast dynamic LH
      rebinding (due to DNA stem destabilization), and low compared to high LH
      concentration (due to DNA stem inhibition). Heterogeneous superbead constructs-
      nucleosome clusters interspersed with extended fiber regions--emerge during
      unfolding of medium-NRL fibers and may be related to those observed
      experimentally. Our work suggests that fast and slow LH binding pools, present
      simultaneously in vivo, might act cooperatively to yield controlled fiber
      unfolding at low forces. Medium-NRL fibers with multiple dynamic LH pools offer
      both flexibility and selective DNA exposure, and may be evolutionarily suitable
      to regulate chromatin architecture and gene expression.

PMID- 21961595
TI  - Optimization of van der Waals energy for protein side-chain placement and design.
AB  - Computational determination of optimal side-chain conformations in protein
      structures has been a long-standing and challenging problem. Solving this problem
      is important for many applications including homology modeling, protein docking,
      and for placing small molecule ligands on protein-binding sites. Programs
      available as of this writing are very fast and reasonably accurate, as measured
      by deviations of side-chain dihedral angles; however, often due to multiple
      atomic clashes, they produce structures with high positive energies. This is
      problematic in applications where the energy values are important, for example
      when placing small molecules in docking applications; the relatively small
      binding energy of the small molecule is drowned by the large energy due to atomic
      clashes that hampers finding the lowest energy state of the docked ligand. To
      address this we have developed an algorithm for generating a set of side-chain
      conformations that is dense enough that at least one of its members would have a
      root mean-square deviation of no more than R A from any possible side-chain
      conformation of the amino acid. We call such a set a side-chain cover set of
      order R for the amino acid. The size of the set is constrained by the energy of
      the interaction of the side chain to the backbone atoms. Then, side-chain cover
      sets are used to optimize the conformation of the side chains given the
      coordinates of the backbone of a protein. The method we use is based on a variety
      of dead-end elimination methods and the recently discovered dynamic programming
      algorithm for this problem. This was implemented in a computer program called
      Octopus where we use side-chain cover sets with very small values for R, such as
      0.1 A, which ensures that for each amino-acid side chain the set contains a
      conformation with a root mean-square deviation of, at most, R from the optimal
      conformation. The side-chain dihedral-angle accuracy of the program is comparable
      to other implementations; however, it has the important advantage that the
      structures produced by the program have negative energies that are very close to
      the energies of the crystal structure for all tested proteins.

PMID- 21961594
TI  - Binding of the molecular chaperone alphaB-crystallin to Abeta amyloid fibrils
      inhibits fibril elongation.
AB  - The molecular chaperone alphaB-crystallin is a small heat-shock protein that is
      upregulated in response to a multitude of stress stimuli, and is found
      colocalized with Abeta amyloid fibrils in the extracellular plaques that are
      characteristic of Alzheimer's disease. We investigated whether this archetypical
      small heat-shock protein has the ability to interact with Abeta fibrils in vitro.
      We find that alphaB-crystallin binds to wild-type Abeta(42) fibrils with
      micromolar affinity, and also binds to fibrils formed from the E22G Arctic
      mutation of Abeta(42). Immunoelectron microscopy confirms that binding occurs
      along the entire length and ends of the fibrils. Investigations into the effect
      of alphaB-crystallin on the seeded growth of Abeta fibrils, both in solution and
      on the surface of a quartz crystal microbalance biosensor, reveal that the
      binding of alphaB-crystallin to seed fibrils strongly inhibits their elongation.
      Because the lag phase in sigmoidal fibril assembly kinetics is dominated by
      elongation and fragmentation rates, the chaperone mechanism identified here
      represents a highly effective means to inhibit fibril proliferation. Together
      with previous observations of alphaB-crystallin interaction with alpha-synuclein
      and insulin fibrils, the results suggest that this mechanism is a generic means
      of providing molecular chaperone protection against amyloid fibril formation.

PMID- 21961596
TI  - Dynamics of thermodynamically stable, kinetically trapped, and inhibitor-bound
      states of pepsin.
AB  - The pepsin folding mechanism involves a prosegment (PS) domain that catalyzes
      folding, which is then removed, resulting in a kinetically trapped native state.
      Although native pepsin (Np) is kinetically stable, it is irreversibly denatured
      due to a large folding barrier, and in the absence of the PS it folds to a more
      thermodynamically stable denatured state, termed refolded pepsin (Rp). This
      system serves as a model to understand the nature of kinetic barriers and folding
      transitions between compact states. Quasielastic neutron scattering (QENS) was
      used to characterize and compare the flexibility of Np, as a kinetically trapped
      state, with that of Rp, as a thermodynamically stable fold. Additionally, the
      dynamics of Np were compared with those of a partially unfolded form and a
      thermally stabilized, inhibitor-bound form. QENS revealed length-scale-dependent
      differences between Np and Rp on a picosecond timescale and indicated greater
      flexibility in Np, leading to the conclusion that kinetic stabilization likely
      does not correspond to reduced internal dynamics. Furthermore, large differences
      were observed upon inhibition, indicating that QENS of proteins in solution may
      prove useful for examining the role of conformational entropy changes in ligand
      binding.

PMID- 21961597
TI  - Single molecule study of the intrinsically disordered FG-repeat nucleoporin 153.
AB  - Nucleoporins (Nups), which are intrinsically disordered, form a selectivity
      filter inside the nuclear pore complex, taking a central role in the vital
      nucleocytoplasmic transport mechanism. These Nups display a complex and nonrandom
      amino-acid architecture of phenylalanine glycine (FG)-repeat clusters and intra
      FG linkers. How such heterogeneous sequence composition relates to function and
      could give rise to a transport mechanism is still unclear. Here we describe a
      combined chemical biology and single-molecule fluorescence approach to study the
      large human Nup153 FG-domain. In order to obtain insights into the properties of
      this domain beyond the average behavior, we probed the end-to-end distance (R(E))
      of several ~50-residues long FG-repeat clusters in the context of the whole
      protein domain. Despite the sequence heterogeneity of these FG-clusters, we
      detected a reoccurring and consistent compaction from a relaxed coil behavior
      under denaturing conditions (R(E)/R(E,RC) = 0.99 +/- 0.15 with R(E,RC)
      corresponding to ideal relaxed coil behavior) to a collapsed state under native
      conditions (R(E)/R(E,RC) = 0.79 +/- 0.09). We then analyzed the properties of
      this protein on the supramolecular level, and determined that this human FG
      domain was in fact able to form a hydrogel with physiological permeability
      barrier properties.

PMID- 21961598
TI  - Chain collapse of an amyloidogenic intrinsically disordered protein.
AB  - Natively unfolded or intrinsically disordered proteins (IDPs) are under intense
      scrutiny due to their involvement in both normal biological functions and
      abnormal protein misfolding disorders. Polypeptide chain collapse of
      amyloidogenic IDPs is believed to play a key role in protein misfolding,
      oligomerization, and aggregation leading to amyloid fibril formation, which is
      implicated in a number of human diseases. In this work, we used bovine kappa
      casein, which serves as an archetypal model protein for amyloidogenic IDPs. Using
      a variety of biophysical tools involving both prediction and spectroscopic
      techniques, we first established that monomeric kappa-casein adopts a collapsed
      premolten-globule-like conformational ensemble under physiological conditions.
      Our time-resolved fluorescence and light-scattering data indicate a change in the
      mean hydrodynamic radius from ~4.6 nm to ~1.9 nm upon chain collapse. We then
      took the advantage of two cysteines separated by 77 amino-acid residues and
      covalently labeled them using thiol-reactive pyrene maleimide. This dual-labeled
      protein demonstrated a strong excimer formation upon renaturation from urea- and
      acid-denatured states under both equilibrium and kinetic conditions, providing
      compelling evidence of polypeptide chain collapse under physiological conditions.
      The implication of the IDP chain collapse in protein aggregation and amyloid
      formation is also discussed.

PMID- 21961599
TI  - Dynamical allosterism in the mechanism of action of DNA mismatch repair protein
      MutS.
AB  - The multidomain protein Thermus aquaticus MutS and its prokaryotic and eukaryotic
      homologs recognize DNA replication errors and initiate mismatch repair. MutS
      actions are fueled by ATP binding and hydrolysis, which modulate its interactions
      with DNA and other proteins in the mismatch-repair pathway. The DNA binding and
      ATPase activities are allosterically coupled over a distance of ~70 A, and the
      molecular mechanism of coupling has not been clarified. To address this problem,
      all-atom molecular dynamics simulations of ~150 ns including explicit solvent
      were performed on two key complexes--ATP-bound and ATP-free MutS?DNA(+T bulge).
      We used principal component analysis in fluctuation space to assess ATP ligand
      induced changes in MutS structure and dynamics. The molecular dynamics-calculated
      ensembles of thermally accessible structures showed markedly small differences
      between the two complexes. However, analysis of the covariance of dynamical
      fluctuations revealed a number of potentially significant interresidue and
      interdomain couplings. Moreover, principal component analysis revealed clusters
      of correlated atomic fluctuations linking the DNA and nucleotide binding sites,
      especially in the ATP-bound MutS?DNA(+T) complex. These results support the idea
      that allosterism between the nucleotide and DNA binding sites in MutS can occur
      via ligand-induced changes in motion, i.e., dynamical allosterism.

PMID- 21961600
TI  - Contribution of unfolding and intermolecular architecture to fibronectin fiber
      extensibility.
AB  - The extracellular matrix contains components with remarkable mechanical
      properties, including fibronectin (Fn) fibers with extensibilities of >700%
      strain. We utilized what we consider a novel technique to quantify the extent of
      molecular unfolding that contributes to Fn fiber extension, and we compared this
      behavior with stochastic models of Fn fibers with different molecular
      arrangements. In vitro unfolding as a function of strain was measured by
      fluorescently labeling cysteines in modules FnIII7 and III15 in artificial Fn
      fibers. A calibration technique we also consider novel made it possible to
      demonstrate that 44% of cysteines in these modules were exposed in Fn fibers
      strained to 421% extension, up from 8% exposure without strain. In silico
      unfolding was measured by applying a constant strain rate to a fiber represented
      by a network of wormlike chain springs, each representing an individual Fn
      molecule. Unfolding rates were calculated with a tension-dependent stochastic
      model applied to FnIII modules in each molecule. A comparison of these approaches
      revealed that only a molecular arrangement permitting unequal mechanical loading
      of Fn molecules recapitulates in vitro unfolding. These data have implications
      for Fn-dependent mechanotransduction and give insight into how the molecular
      architecture of natural materials permits such remarkable extensibility.

PMID- 21961601
TI  - High-throughput analysis of concentration-dependent antibody self-association.
AB  - Monoclonal antibodies are typically monomeric and nonviscous at low
      concentrations, yet they display highly variable associative and viscous behavior
      at elevated concentrations. Although measurements of antibody self-association
      are critical for understanding this complex behavior, traditional biophysical
      methods are not capable of characterizing such concentration-dependent self
      association in a high-throughput manner. Here we describe a nanoparticle-based
      method, termed self-interaction nanoparticle spectroscopy, that is capable of
      rapidly measuring concentration-dependent self-interactions for three human
      monoclonal antibodies with unique solution behaviors. We demonstrate that gold
      nanoparticles conjugated with antibodies at low protein concentrations (<40
      MUg/mL) display self-association behavior (as measured by the interparticle
      distance-dependent plasmon wavelength) that is well correlated with static light
      scattering measurements obtained at three orders of magnitude higher antibody
      concentrations. Using this methodology, we find that the antibodies display a
      complex pH-dependent self-association behavior that is strongly influenced by the
      solution ionic strength. Importantly, we find that a polyclonal human antibody is
      nonassociative for all solution conditions evaluated in this work, suggesting
      that antibody self-association is more specific than previously realized. We
      expect that our findings will guide rational manipulation of antibody phase
      behavior, and enable studies that elucidate sequence and structural determinants
      of antibody self-association.

PMID- 21961602
TI  - Local conformational flexibility provides a basis for facile polymer formation in
      human neuroserpin.
AB  - Neuroserpin is a regulator of neuronal growth and plasticity. Like other members
      of the serpin family, neuroserpin undergoes a large conformational change as part
      of its function. Unlike other serpins such as alpha(1)-antitrypsin, wild-type
      neuroserpin will polymerize under near-physiological conditions, and will
      spontaneously transition to the latent state. To probe the origins of this
      conformational lability, we have performed hydrogen exchange measurements and
      molecular-dynamics simulations on human neuroserpin. Hydrogen exchange indicates
      that neuroserpin has greater flexibility in the breach region and in beta-strand
      1C compared with alpha(1)-antitrypsin. Molecular-dynamics simulations show that
      the distance between the top of beta-strands 3 and 5A averages 4.6 A but becomes
      as large as 7.5 A in neuroserpin while it remains stable at ~3.5 A in alpha(1)
      antitrypsin. Further simulations show that the stabilizing S340A mutation
      suppresses these fluctuations in neuroserpin. The first principal component
      calculated from the simulations shows a movement of helix F away from the face of
      beta-sheet A in neuroserpin while no such movement is evident in alpha(1)
      antitrypsin. The increased mobility of these regions in neuroserpin relative to
      alpha(1)-antitrypsin provides a basis for neuroserpin's increased tendency toward
      the formation of polymers and/or the latent state.

PMID- 21961603
TI  - Three force fields' views of the 3(10) helix.
AB  - Slowly but steadily bibliographic evidence is accumulating that the apparent
      convergence of the various biomolecular force fields as evidenced from
      simulations of proteins in the folded state does not hold true for folding
      simulations. Here we add one more example to the growing list of peptides and
      proteins for which different force fields show irreconcilable differences in
      their folding predictions, even at such a fundamental level as that of a
      peptide's secondary structure. We show that for an undecamer peptide that is
      known from two independent NMR structure determinations to have a mainly 3(10)
      helical structure in solution, three mainstream biomolecular force fields give
      completely disparate predictions: The CHARMM force field (with the CMAP
      correction) predicts an outstandingly stable alpha-helical structure, in
      disagreement not only with the experimental structures, but also with
      experimental evidence obtained from circular dichroism. OPLS-AA shows an almost
      totally disordered peptide with the most frequently observed folded conformation
      corresponding to a beta-hairpin-like structure, again in disagreement with all
      available experimental evidence. Only the AMBER99SB force field appears to
      qualitatively agree with not only the general structural characteristics of the
      peptide (on the account of both NMR- and CD-based experiments), but to also
      correctly predict some of the experimentally observed interactions at the level
      of side chains. Possible interpretations of these findings are discussed.

PMID- 21961604
TI  - Monomeric and dimeric conformation of the vinculin tail five-helix bundle in
      solution studied by EPR spectroscopy.
AB  - The cytoskeletal adaptor protein vinculin plays an important role in the control
      of cell adhesion and migration, linking the actin cytoskeleton to adhesion
      receptor complexes in cell adhesion sites. The conformation of the vinculin tail
      dimer, which is crucial for protein function, was analyzed using site-directed
      spin labeling in electron paramagnetic resonance spectroscopy. Interspin
      distances for a set of six singly and four doubly spin-labeled mutants of the
      tail domain of vinculin were determined and used as constraints for modeling of
      the vinculin tail dimer. A comparison of the results obtained by molecular
      dynamic simulations and a rotamer library approach reveals that the crystal
      structure of the vinculin tail monomer is essentially preserved in aqueous
      solution. The orientation of monomers within the dimer observed previously by x
      ray crystallography agrees with the solution electron paramagnetic resonance
      data. Furthermore, the distance between positions 1033 is shown to increase by >3
      nm upon interaction of the vinculin tail domain with F-actin.

PMID- 21961605
TI  - Characterization of enhanced monovalent and bivalent thrombin DNA aptamer binding
      using single molecule force spectroscopy.
AB  - Thrombin aptamer binding strength and stability is dependent on sterical
      parameters when used for atomic force microscopy sensing applications. Sterical
      improvements on the linker chemistry were developed for high-affinity binding.
      For this we applied single molecule force spectroscopy using two enhanced
      biotinylated thrombin aptamers, BFF and BFA immobilized on the atomic force
      microscopy tip via streptavidin. BFF is a dimer composed of two single-stranded
      aptamers (aptabody) connected to each other by a complementary sequence close to
      the biotinylated end. In contrast, BFA consists of a single DNA strand and a
      complementary strand in the supporting biotinylated part. By varying the pulling
      velocity in force-distance cycles the formed thrombin-aptamer complexes were
      ruptured at different force loadings allowing determination of the energy
      landscape. As a result, BFA aptamer showed a higher binding force at the
      investigated loading rates and a significantly lower dissociation rate constant,
      k(off), compared to BFF. Moreover, the potential of the aptabody BFF to form a
      bivalent complex could clearly be demonstrated.

PMID- 21961606
TI  - Whole-cell imaging at nanometer resolutions using fast and slow focused helium
      ions.
AB  - Observations of the interior structure of cells and subcellular organelles are
      important steps in unraveling organelle functions. Microscopy using helium ions
      can play a major role in both surface and subcellular imaging because it can
      provide subnanometer resolutions at the cell surface for slow helium ions, and
      fast helium ions can penetrate cells without a significant loss of resolution.
      Slow (e.g., 10-50 keV) helium ion beams can now be focused to subnanometer
      dimensions (~0.25 nm), and keV helium ion microscopy can be used to image the
      surfaces of cells at high resolutions. Because of the ease of neutralizing the
      sample charge using a flood electron beam, surface charging effects are minimal
      and therefore cell surfaces can be imaged without the need for a conducting
      metallic coating. Fast (MeV) helium ions maintain a straight path as they pass
      through a cell. Along the ion trajectory, the helium ion undergoes multiple
      electron collisions, and for each collision a small amount of energy is lost to
      the scattered electron. By measuring the total energy loss of each MeV helium ion
      as it passes through the cell, we can construct an energy-loss image that is
      representative of the mass distribution of the cell. This work paves the way to
      use ions for whole-cell investigations at nanometer resolutions through
      structural, elemental (via nuclear elastic backscattering), and fluorescence (via
      ion induced fluorescence) imaging.

PMID- 21961607
TI  - Interactive, computer-assisted tracking of speckle trajectories in fluorescence
      microscopy: application to actin polymerization and membrane fusion.
AB  - Analysis of particle trajectories in images obtained by fluorescence microscopy
      reveals biophysical properties such as diffusion coefficient or rates of
      association and dissociation. Particle tracking and lifetime measurement is often
      limited by noise, large mobilities, image inhomogeneities, and path crossings. We
      present Speckle TrackerJ, a tool that addresses some of these challenges using
      computer-assisted techniques for finding positions and tracking particles in
      different situations. A dynamic user interface assists in the creation, editing,
      and refining of particle tracks. The following are results from application of
      this program: 1), Tracking single molecule diffusion in simulated images. The
      shape of the diffusing marker on the image changes from speckle to cloud,
      depending on the relationship of the diffusion coefficient to the camera exposure
      time. We use these images to illustrate the range of diffusion coefficients that
      can be measured. 2), We used the program to measure the diffusion coefficient of
      capping proteins in the lamellipodium. We found values ~0.5 MUm(2)/s, suggesting
      capping protein association with protein complexes or the membrane. 3), We
      demonstrate efficient measuring of appearance and disappearance of EGFP-actin
      speckles within the lamellipodium of motile cells that indicate actin monomer
      incorporation into the actin filament network. 4), We marked appearance and
      disappearance events of fluorescently labeled vesicles to supported lipid
      bilayers and tracked single lipids from the fused vesicle on the bilayer. This is
      the first time, to our knowledge, that vesicle fusion has been detected with
      single molecule sensitivity and the program allowed us to perform a quantitative
      analysis. 5), By discriminating between undocking and fusion events, dwell times
      for vesicle fusion after vesicle docking to membranes can be measured.

PMID- 21961608
TI  - Body Mass Index standards based on agreement with health-related body fat.
AB  - BACKGROUND: Multiple screening tools, such as BMI and skinfold-derived percent
      body fat (%BF), are available to identify youth at risk of excess adiposity.
      However, poor classification agreement among these tools can be problematic for
      those interpreting test results. PURPOSE: The purpose of this study was to
      investigate the validity of using BMI as an estimate of %BF in youth and to
      identify optimal BMI thresholds for identifying at-risk children and adolescents
      based on %BF. METHODS: Percent body fat was derived from the skinfold thicknesses
      of children aged 5-18 years from three cross-sectional waves of the National
      Health and Nutrition Examination Survey (NHANES [1999-2004]; N=8269). Stature and
      body mass from the same data set were used to calculate BMI. Receiver operating
      characteristic (ROC) analysis was employed to determine the optimal BMI
      thresholds for detecting previously created %BF standards. RESULTS: The optimal
      BMI percentile associated with the low risk %BF threshold was the 83 rd and 80th
      in boys and girls, respectively. The selected BMI percentiles associated with the
      higher risk threshold were the 92 nd and 90th in boys and girls, respectively.
      Overall, classification accuracy when using BMI percentiles to identify the two
      %BF risk groups ranged from 86.9% to 89.1%. CONCLUSIONS: BMI and skinfold-derived
      %BF demonstrate reasonable agreement when used to classify adiposity status in
      children and adolescents.

PMID- 21961609
TI  - Aerobic fitness percentiles for U.S. adolescents.
AB  - BACKGROUND: Although aerobic fitness has been well studied, establishing
      developmental patterns from previous studies has some limitations including
      selection bias and the statistical modeling of growth-related data. PURPOSE: The
      purpose of this study was to develop age-, gender-, and race-specific smoothed
      percentiles for aerobic fitness using the LMS (L=skewness, M=median, and
      S=coefficient of variation) statistical procedure in a large, multiethnic,
      nationally representative sample of U.S. adolescents aged 12-18 years. METHODS:
      Data from the National Health and Nutrition Examination Survey (NHANES [1999-2000
      and 2001-2002]) were combined. In all, 2997 subjects (1478 boys and 1519 girls)
      completed a treadmill exercise test from which maximal oxygen consumption
      (VO(2)max) was estimated from heart rate response. Percentile curves were
      determined by using the LMS procedure, which fits smooth percentile curves to
      reference data. RESULTS: Separate LMS curves were initially prepared for each
      gender and race; however, since the overall distribution of the data was not
      different for whites, blacks, and Hispanics, the participants were combined, and
      separate centile curves were prepared for boys and girls. Specific percentile
      values were created from the LMS curves, and the age- and gender-specific values
      for LMS are provided for calculation of individual z-scores (SD scores). In
      general, there is a slight increase in estimated VO(2)max of boys aged 12-15
      years and then it remains stable. In girls, there is slight decrease in estimated
      VO(2)max across ages 12-18 years. Boys have higher values than girls at every age
      specific percentile. CONCLUSIONS: This study presents age- and gender-specific
      percentiles for U.S. youth aged 12-18 years based on NHANES (1999-2002), and adds
      to the recent application of the LMS statistical procedure for the construction
      of growth percentiles for a variety of outcomes. Comparisons are made to current
      FITNESSGRAM((r)) thresholds.

PMID- 21961610
TI  - Development of youth aerobic-capacity standards using receiver operating
      characteristic curves.
AB  - BACKGROUND: Cardiovascular fitness has important implications for current and
      future health in children. PURPOSE: In this paper, criterion-referenced standards
      are developed for aerobic capacity (an indicator of cardiovascular fitness) based
      on receiver operating characteristic (ROC) curves. METHODS: The sample was drawn
      from participants aged 12-18 years in the National Health and Nutrition
      Examination Survey (1999-2002, N=1966). Subjects completed a treadmill exercise
      test from which maximal oxygen uptake (VO(2)max) was estimated from heart rate
      response. Metabolic syndrome was classified using previously published standards
      based on the National Cholesterol Education Program/Adult Treatment Panel III
      adult values at age 20 years. Using aerobic fitness z-scores as the test and
      metabolic syndrome as the criterion, ROC curve analysis was used to identify
      aerobic-capacity thresholds. RESULTS: The area under the curve (AUC) value for
      boys (83.1%) was high, indicating good utility for detecting risk of metabolic
      syndrome with aerobic fitness values. The AUC for girls (77.2%) was slightly
      below the recommended value of 80%. Although the ROC plots identified a
      defensible point for classifying levels of fitness, the approach in the present
      study was to establish two independent thresholds, one aimed at high specificity
      and one aimed at high sensitivity. The resulting z values for the low- and higher
      risk threshold lines were then converted back to VO(2)max estimates using
      published LMS (L=skewness, M=median, and S=coefficient of variation) parameters.
      Values at the low-risk threshold ranged from 40 to 44 mL/kg/min for boys and from
      38 to 40 mL/kg/min for girls. CONCLUSIONS: In summary, aerobic fitness can be
      used with moderate accuracy to differentiate between adolescents with and without
      metabolic syndrome. Age- and gender-specific aerobic-capacity thresholds for
      creating separate risk groups were identified using nationally representative
      growth percentiles.

PMID- 21961611
TI  - Estimation of aerobic fitness from 20-m multistage shuttle run test performance.
AB  - BACKGROUND: Aerobic fitness (VO(2)max) is a key component of youth fitness
      testing. Criterion-referenced (CR) assessments are used in FITNESSGRAM((r)) to
      assess health risk. PURPOSE: The purpose of this study was to develop and cross
      validate regression models to estimate VO(2)max from Progressive Aerobic
      Cardiovascular Endurance Run (PACER) 20-m shuttle run performance in boys and
      girls aged 10-16 years. Several previously published PACER models were also cross
      validated. A secondary purpose was to examine the CR validity of the models.
      METHODS: PACER performance and VO(2)max were assessed in a sample of 244
      participants. The sample was randomly split into validation (n=174) and cross
      validation (n=70) samples. The validation sample was used to develop the
      regression models to estimate VO(2)max from PACER, BMI, gender, and age. CR
      validity was evaluated by comparing classification of the prediction models with
      classification by the criterion of measured VO(2)max. RESULTS: For the Quadratic
      Model, the multiple correlation between measured and estimated VO(2)max was 0.75,
      and the SE of estimate (SEE) was 6.17 mL/kg/min. Similar accuracy was found for
      Linear Model 2 (R=0.74; SEE=6.29 mL/kg/min). Accuracy of these models was
      confirmed on the cross-validation and total samples. Cross-validation
      demonstrated that the Quadratic Model and Linear Model 2 were slightly more
      accurate than previous PACER models. Evidence of CR validity for the newly
      developed models was of moderate levels. CONCLUSIONS: The Quadratic Model and
      Linear Model 2 provide valid estimates of VO(2)max and compare favorably to
      previous models. The CR validity evidence for the Quadratic Model and Linear
      Models developed in this study was slightly better than for the other models
      examined.

PMID- 21961612
TI  - Cross-validation of an equating method linking aerobic FITNESSGRAM(r) field
      tests.
AB  - BACKGROUND: Field tests measuring the same construct, in this case, aerobic
      capacity, use different scales, which makes fitness assessment of children and
      youth potentially confusing. The Primary Field Test Centered Equating Method has
      been developed to set tests on the same scale, as illustrated by the conversion
      of Progressive Aerobic Capacity Endurance Run (PACER) scores to 1-mile run/walk
      times to estimate VO(2)max. PURPOSE: The purpose of this study was to cross
      validate the Primary Field Test Centered Equating Method by using a data set of
      middle school students to assess its effectiveness. METHODS: PACER scores of 135
      middle school students were converted to 1-mile run/walk times (Mile PEQ) using
      the proposed method. Several estimates of VO(2)max using PACER scores were then
      compared to estimated VO(2)max using Mile PEQ and measured VO(2)max. The obtained
      measures were classified according to the healthy fitness zone (HFZ;
      FITNESSGRAM((r)), version 9) and compared to measured VO(2)max. BMI estimates
      based on the sample data and the national average also were considered to assess
      the method's flexibility. RESULTS: Agreement levels with actual values were
      similar for VO(2)max predicted using Mile PEQ and predictions using PACER laps
      and speed (73%-75%). The t-tests showed no significant difference between actual
      VO(2)max (M=44.43, SD= 8.36) and VO(2)max predicted using Mile PEQ (M=44.33,
      SD=5.88). Using BMI averages from sample data and the national data to estimate
      VO(2)max using Mile PEQ also yields high agreement levels, 70% and 73%,
      respectively. CONCLUSIONS: The Primary Field Test Centered Equating Method
      performs as well or better in estimating VO(2)max as several other models using
      PACER scores, especially for boys, and thus may be successfully used in practice.
      More research is needed to understand the relatively low prediction and
      classification accuracy in girls.

PMID- 21961613
TI  - Field evaluation of the new FITNESSGRAM(r) criterion-referenced standards.
AB  - BACKGROUND: The Cooper Institute established new criterion-referenced standards
      for the body composition and cardiovascular fitness standards for the
      FITNESSGRAM((r)) program. PURPOSE: The purpose of this study was to evaluate
      differences in the achievement of standards and classification agreement between
      the old and new standards. METHODS: Fitness data were collected during the 2009
      2010 school year from 1686 youth (grades 3-12) from six schools (two districts)
      in a small Midwestern town. Data analyses were completed during the 2010 and 2011
      school year. Descriptive statistics were computed to determine the percentage of
      students classified into the various fitness classifications using both the old
      and new standards. Classification agreement was examined for alternative tests of
      cardiovascular fitness (Progressive Aerobic Cardiovascular Endurance Run [PACER]
      and 1-mile run) and body composition (skinfold determination of body fat and BMI)
      using both the old and new standards. RESULTS: The descriptive results reveal
      important age and gender differences in reported levels of fitness levels in
      school-aged youth. For body composition, the percentage of youth achieving the
      healthy fitness zone (HFZ) was about 10% lower with the new standards than the
      old ones. For aerobic capacity, a larger percentage of young boys and a smaller
      percentage of older boys achieved the new HFZ for aerobic capacity. However, a
      smaller percentage of girls achieved the new HFZ at all ages. The use of test
      equating in the revised standards led to significant improvements in the
      classification agreement between 1-mile run and the PACER. CONCLUSIONS: The large
      data set provided a useful sample to examine the impact of the new fitness
      standards on the documentation of youth fitness levels in schools. The new
      standards address a number of measurement issues with the old standards and
      provide a more appropriate way to evaluate levels of health-related fitness in
      youth.

PMID- 21961614
TI  - Development of new criterion-referenced fitness standards in the FITNESSGRAM(r)
      program: rationale and conceptual overview.

PMID- 21961615
TI  - Approaches for development of criterion-referenced standards in health-related
      youth fitness tests.

PMID- 21961616
TI  - Percent body fat and chronic disease risk factors in U.S. children and youth.
AB  - BACKGROUND: The dramatic increase in pediatric obesity has renewed interest in
      accurate methods and screening indexes for identifying at-risk children and
      youth. Whether age-specific standards are needed is a factor that remains
      uncertain. PURPOSE: This study was designed to describe the age-specific fatness
      risk factor relationship in boys and girls across a wide age range. METHODS: Data
      were from 12,279 white, black, and Mexican-American children and adolescents from
      the National Health and Nutritional Examination Surveys (NHANES) III (1998-1994)
      and IV (1999-2004). Children were grouped based on percent fat, estimated from
      subscapular and triceps skinfolds, and the age-specific relationships between
      percent fat and chronic disease risk factors (e.g., blood pressure, lipids and
      lipoprotein levels, glucose, insulin, and circulating C-reactive protein levels)
      were described in boys and girls, aged 6-18 years. RESULTS: Percent fat was
      significantly related to risk factor levels. At higher levels of percent fat, the
      prevalence of adverse cardiovascular disease risk factors was higher,
      particularly above 20% fat in boys and above 30% fat in girls. In boys and girls,
      the interaction term age by percent fat was a significant predictor of risk
      factors, whereas the percent fat by race interaction term was nonsignificant.
      CONCLUSIONS: The results demonstrate a strong relationship between chronic
      disease risk factors and percent fat in children and youth that varies by age in
      boys and girls.

PMID- 21961617
TI  - Body fat percentile curves for U.S. children and adolescents.
AB  - BACKGROUND: To date, several studies have been published outlining reference
      percentiles for BMI in children and adolescents. In contrast, there are limited
      reference data on percent body fat (%BF) in U.S. youth. PURPOSE: The purpose of
      this study was to derive smoothed percentile curves for %BF in a nationally
      representative sample of U.S. children and adolescents. METHODS: Percent fat was
      derived from the skinfold thicknesses of those aged 5-18 years from three cross
      sectional waves of the National Health and Nutrition Examination Survey (NHANES)
      IV (1999-2000, 2001-2002, and 2003-2004; N=8269). The LMS (L=skewness, M=median,
      and S=coefficient of variation) regression method was used to create age- and
      gender-specific smoothed percentile curves of %BF. RESULTS: Growth curves are
      similar between boys and girls until age 9 years. However, whereas %BF peaks for
      boys at about age 11 years, it continues to increase for girls throughout
      adolescence. Median %BF at age 18 years is 17.0% and 27.8% for boys and girls,
      respectively. CONCLUSIONS: Growth charts and LMS values based on a nationally
      representative sample of U.S. children and adolescents are provided so that
      future research can identify appropriate cut-off values based on health-related
      outcomes. These percentiles are based on skinfolds, which are widely available
      and commonly used. Using %BF instead of BMI may offer additional information in
      epidemiologic research, fitness assessment, and clinical settings.

PMID- 21961618
TI  - Development of youth percent body fat standards using receiver operating
      characteristic curves.
AB  - BACKGROUND: Few studies have identified health-related criterion standards of
      percent body fat (%BF) in U.S. youth. Further, existing standards are static
      thresholds (e.g., 25%, 30%) and do not account for normal growth and maturation.
      PURPOSE: The purpose of this study was to identify thresholds of %BF in youth
      linked to metabolic syndrome in a large sample of U.S. children and adolescents.
      METHODS: Percent fat was derived from the skinfold thicknesses of those aged 12
      18 years, from the National Health and Nutrition Examination Survey (NHANES [1999
      2004, N=1966]). Metabolic syndrome was classified using previously published
      standards based on the National Cholesterol Education Program/Adult Treatment
      Panel III adult values at age 20 years. Using %BF z-scores as the test and
      metabolic syndrome as the criterion, receiver operating characteristic (ROC)
      curve analysis was used to identify %BF thresholds. RESULTS: ROC analysis
      indicated that %BF can be used with moderate accuracy to identify metabolic
      syndrome in adolescents. %BF thresholds of 22.3% and 35.1% in boys and 31.4% and
      38.6% in girls (at age 18 years) were found to be indicative of "low" and "high"
      metabolic syndrome risk. CONCLUSIONS: Age- and gender-specific %BF thresholds for
      creating separate risk groups were identified in relation to metabolic syndrome
      status. The selected thresholds identify adolescents with unfavorable metabolic
      profiles. These values could be extrapolated to younger children using previously
      created %BF centiles, which potentially allows for earlier identification and
      intervention of at-risk youth if tracking of current %BF was maintained.

PMID- 21961623
TI  - Vulvar squamous cell carcinoma with sarcoma-like stroma: a case report and review
      of the literature.
AB  - Vulvar squamous cell carcinoma with sarcoma-like stroma represents an extremely
      rare histological entity showing the co-existence of both epithelial and
      mesenchymal features: these tumors, firstly described in the skin by Martin and
      Stewart in 1935 have been further described in other anatomic sites including
      oral cavity, larynx, breast, lung and oesophagus. The complexity of the
      histology, as well as its aggressive clinical behaviour makes the diagnosis and
      the exploitment of effective therapeutic approaches very difficult, so that no
      definitive guidelines for treatments are currently available. Here, we describe a
      case of advanced stage vulvar squamous cell carcinoma with sarcoma-like stroma
      showing an unfavourable prognosis despite the use of an aggressive multimodal
      approach. A revision of the currently published cases have been also provided.

PMID- 21961624
TI  - Methodology for the development of a Canadian national EMS research agenda.
AB  - BACKGROUND: Many health care disciplines use evidence-based decision making to
      improve patient care and system performance. While the amount and quality of
      emergency medical services (EMS) research in Canada has increased over the past
      two decades, there has not been a unified national plan to enable research,
      ensure efficient use of research resources, guide funding decisions and build
      capacity in EMS research. Other countries have used research agendas to identify
      barriers and opportunities in EMS research and define national research
      priorities. The objective of this project is to develop a national EMS research
      agenda for Canada that will: 1) explore what barriers to EMS research currently
      exist, 2) identify current strengths and opportunities that may be of benefit to
      advancing EMS research, 3) make recommendations to overcome barriers and
      capitalize on opportunities, and 4) identify national EMS research priorities.
      METHODS/DESIGN: Paramedics, educators, EMS managers, medical directors,
      researchers and other key stakeholders from across Canada will be purposefully
      recruited to participate in this mixed methods study, which consists of three
      phases: 1) qualitative interviews with a selection of the study participants, who
      will be asked about their experience and opinions about the four study
      objectives, 2) a facilitated roundtable discussion, in which all participants
      will explore and discuss the study objectives, and 3) an online Delphi consensus
      survey, in which all participants will be asked to score the importance of each
      topic discovered during the interviews and roundtable as they relate to the study
      objectives. Results will be analyzed to determine the level of consensus achieved
      for each topic. DISCUSSION: A mixed methods approach will be used to address the
      four study objectives. We anticipate that the keys to success will be: 1)
      ensuring a representative sample of EMS stakeholders, 2) fostering an open and
      collaborative roundtable discussion, and 3) adhering to a predefined approach to
      measure consensus on each topic. Steps have been taken in the methodology to
      address each of these a priori concerns.

PMID- 21961625
TI  - Does self-regulation and autonomic regulation have an influence on survival in
      breast and colon carcinoma patients? results of a prospective outcome study.
AB  - BACKGROUND: Cancer Related Fatigue (CRF) and circadian rhythm have a great impact
      on the quality of life (HRQL) of patients with breast (BC) and colon cancer
      (CRC). Other patient related outcomes in oncology are measured by new instruments
      focusing on adaptive characteristics such as sense of coherence or self
      regulation, which could be more appropriate as a prognostic tool than classical
      HRQL. The aim of this study was to assess the association of autonomic regulation
      (aR) and self-regulation (SR) with survival. METHODS: 146 cancer patients and 120
      healthy controls took part in an initial evaluation in 2000/2001. At a median
      follow up of 5.9 years later, 62 of 95 BC, 17 of 51 CRC patients, and 85 of 117
      healthy controls took part in the follow-up study. 41 participants had died. For
      the follow-up evaluation, participants were requested to complete the
      standardized aR and SR questionnaires. RESULTS: On average, cancer patients had
      survived for 10.1 years with the disease. Using a Cox proportional hazard
      regression with stepwise variables such as age, diagnosis group, Charlson co
      morbidity index, body mass index (BMI)) aR and SR. SR were identified as
      independent parameters with potential prognostic relevance on survival While aR
      did not significantly influence survival, SR showed a positive and independent
      impact on survival (OR = 0.589; 95%-CI: 0.354 - 0.979). This positive effect
      persisted significantly in the sensitivity analysis of the subgroup of tumour
      patients and in the subscale 'Achieve satisfaction and well-being' and by
      tendency in the UICC stages nested for the different diagnoses groups.
      CONCLUSIONS: Self-regulation might be an independent prognostic factor for the
      survival of breast and colon carcinoma patients and merits further prospective
      studies.

PMID- 21961628
TI  - Severe infestation of bedbugs in a poultry breeder house.

PMID- 21961629
TI  - What is your diagnosis? Plasma cell tumor.

PMID- 21961630
TI  - Diagnostic imaging in veterinary dental practice. Mandibular fractures diagnosed
      by radiography.

PMID- 21961631
TI  - Anesthesia case of the month. Malignant hyperthermia.

PMID- 21961632
TI  - Pathology in practice. Congenital mesoblastic nephroma.

PMID- 21961633
TI  - Wrapping it all up. Statistics in veterinary medicine. Flowcharts.

PMID- 21961634
TI  - Employment, starting salaries, and educational indebtedness of year-2011
      graduates of US veterinary medical colleges.

PMID- 21961635
TI  - Identification of the most common cutaneous neoplasms in dogs and evaluation of
      breed and age distributions for selected neoplasms.
AB  - OBJECTIVE-To identify the most common cutaneous neoplasms in dogs and evaluate
      breed and age distributions for selected neoplasms. DESIGN-Retrospective
      epidemiological study. SAMPLE-Records available through the Veterinary Medical
      Database of dogs examined at veterinary teaching hospitals in North America
      between 1964 and 2002. PROCEDURES-Information on tumor type and patient breed and
      age was collected. Incidence and odds ratios with 95% confidence intervals were
      calculated. RESULTS-Records of 1,139,616 dogs were reviewed. Cutaneous neoplasms
      were diagnosed in 25,996 of these dogs; records for the remaining 1,113,620 dogs
      did not indicate that cutaneous neoplasms had been diagnosed, and these dogs were
      considered controls. The most frequent age range for dogs with cutaneous
      neoplasms was 10 to 15 years. Lipoma, adenoma, and mast cell tumor were the most
      common skin tumor types. CONCLUSIONS AND CLINICAL RELEVANCE-Results supported
      previously reported data regarding cutaneous neoplasia in dogs but provided
      updated information on the most common skin tumors and on age and breed
      distributions.

PMID- 21961637
TI  - Clinical characteristics, treatment, and outcome of dogs with presumed primary
      hepatic lymphoma: 18 cases (1992-2008).
AB  - OBJECTIVE-To determine outcome of dogs with presumed primary hepatic lymphoma
      treated with various multiagent, doxorubicin-based chemotherapeutic protocols and
      identify factors associated with prognosis. DESIGN-Retrospective case series.
      ANIMALS-18 dogs with presumed primary hepatic lymphoma. PROCEDURES-Medical
      records were reviewed for information on signalment, treatment, and outcome.
      RESULTS-8 dogs had a complete remission (CR), with a median remission duration of
      120 days. Dogs with leukocytosis, neutrophilia, hypoalbuminemia,
      hyperbilirubinemia, or a combination of hypoalbuminemia and hyperbilirubinemia
      were less likely to achieve a CR. Overall median survival time (MST) was 63 days
      (range, 2 to 402 days). In a multivariate analysis, response to treatment and
      serum albumin concentration were associated with MST. Dogs that did not achieve a
      CR had a significantly shorter MST than did dogs that did achieve a CR (13 vs 283
      days, respectively). Dogs with serum albumin concentration < 2.5 g/dL at the time
      treatment was initiated had a significantly shorter MST than did dogs with serum
      albumin concentration within reference limits (10 vs 128 days, respectively).
      There was also a positive correlation between serum albumin concentration and
      survival time (r = 0.74). CONCLUSIONS AND CLINICAL RELEVANCE-Results suggested
      that dogs with primary hepatic lymphoma that underwent chemotherapy had a poor
      prognosis, with a low response rate. Dogs that responded to treatment had a
      better prognosis, and dogs with hypoalbuminemia had a poorer prognosis.

PMID- 21961638
TI  - Vaginal resection and anastomosis for treatment of vestibulovaginal stenosis in 4
      dogs with recurrent urinary tract infections.
AB  - CASE DESCRIPTION-4 dogs were evaluated because of recurrent urinary tract
      infections. CLINICAL FINDINGS-All dogs had recurrent urinary tract infections and
      similar clinical signs; 3 dogs had urinary incontinence. Digital vaginal
      examination revealed vestibulovaginal stenosis in all dogs, which was confirmed
      by results of contrast vaginourethrography. From image measurements, the
      vestibulovaginal ratio (ratio of the height of the vestibulovaginal junction to
      the maximum height of the vagina on a lateral vaginourethrogram) was calculated
      for each dog. Three dogs had severe stenosis (vestibulovaginal ratio, < 0.20;
      severe stenosis is defined as a vestibulovaginal ratio < 0.20), whereas the
      fourth dog had moderate stenosis (vestibulovaginal ratio, 0.24; ratio range for
      moderate stenosis is 0.20 to 0.25). TREATMENT AND OUTCOME-All dogs were
      anesthetized for surgical correction of the vestibulovaginal stenosis. Vaginal
      resection and anastomosis of the stenosis was performed in all 4 dogs, with 1 dog
      also undergoing episioplasty. Complete resolution of clinical signs was apparent
      in 3 dogs; 1 dog had postoperative complications including pollakiuria and
      stranguria, which resulted in rectal and vaginal prolapse. This dog underwent
      ovariohysterectomy, after which clinical signs resolved. All dogs had resolution
      of urinary tract infections at the time of follow-up (6 to 8 months after
      surgery). CLINICAL RELEVANCE-Resection and anastomosis may resolve recurrent
      urinary tract infections in dogs with severe or moderate vestibulovaginal
      stenosis. Episiotomy was not necessary for success of surgical treatment, and
      overall, that procedure increased morbidity, the severity of intraoperative
      hemorrhage, and duration of surgery.

PMID- 21961639
TI  - Cystic ectopic lingual thyroid tissue in a male cat.
AB  - CASE DESCRIPTION-A 6-year-old neutered male cat was examined because of a 4-week
      history of abnormal sounds while drinking and a previously noted mass at the base
      of the tongue. CLINICAL FINDINGS-Oral examination revealed a 1-cm-diameter
      midline cystic mass on the dorsal aspect of the base of the tongue at the
      junction of the rostral two-thirds and caudal third of the tongue. Complete blood
      count and serum biochemical analysis revealed no clinically relevant
      abnormalities, and serum total thyroxine and free thyroxine (determined by
      equilibrium dialysis) concentrations were within the reference range. TREATMENT
      AND OUTCOME-The fluid in the cystic mass was aspirated, and the remaining
      deflated mass was marsupialized. Histologic and immunohistochemical examination
      of sections of the excised mass revealed ectopic thyroid tissue. The cat
      recovered uneventfully from the surgery, clinical signs resolved, and the cat
      remained euthyroid with no recurrence of the mass as of 8 months after surgery.
      CLINICAL RELEVANCE-This is the first known reported case of ectopic lingual
      thyroid tissue in a male cat. In humans, the most common site of ectopic thyroid
      tissue is at the base of the tongue and the condition is disproportionately found
      in females, compared with males. In humans with ectopic lingual thyroid tissue,
      the patient often lacks any other functional thyroid tissue. However, the cat of
      this report remained euthyroid after mass resection.

PMID- 21961640
TI  - Diagnosis and management of lymphoma in a green iguana (Iguana iguana).
AB  - CASE DESCRIPTION-A 2-year-old female green iguana was examined for anorexia and
      swelling and pain on palpation in the cranial cervical area. CLINICAL FINDINGS
      Marked soft tissue swelling in the cranial cervical area with corresponding
      cystic swellings in the pharynx were noted. The iguana was considered to be 50%
      under the expected body weight, given diet and husbandry conditions. The WBC
      count was markedly elevated, characterized by heterophilia and lymphocytosis.
      Surgical exploration of the cranial cervical area and histologic and microbial
      testing identified lymphoma with secondary infection as the cause of the
      swelling. TREATMENT AND OUTCOME-The tumor was initially treated with a single 10
      Gy fraction of radiation directed at the masses in the neck. A vascular access
      port was placed in the ventral abdominal vein, and a canine chemotherapy protocol
      was modified for use in the iguana. During the course of treatment, the protocol
      was modified twice. At 1,008 days from the initiation of treatment, the iguana
      appeared to be in remission. CLINICAL RELEVANCE-To our knowledge, this is the
      first reported use of radiation with doxorubicin, vincristine, cyclophosphamide,
      and prednisone to successfully manage lymphoma in a reptile. A vascular access
      port was used effectively for drug administration for an extended period. The
      doxorubicin, vincristine, cyclophosphamide, and prednisone protocol appeared to
      be safe and effective in this iguana for the management of lymphoma.

PMID- 21961641
TI  - Intralesional injection of insulin-like growth factor-I for treatment of
      superficial digital flexor tendonitis in Thoroughbred racehorses: 40 cases (2000
      2004).
AB  - OBJECTIVE-To evaluate outcome after intralesional injection of insulin-like
      growth factor-I (IGF-I) for treatment of superficial digital flexor (SDF)
      tendonitis in Thoroughbred racehorses. DESIGN-Retrospective case series. ANIMALS
      40 Thoroughbred racehorses. PROCEDURES-Medical records of racehorses with SDF
      tendonitis treated within 13 weeks after injury by intralesional injection of IGF
      I (25 or 50 MUg every other day for 4 or 5 treatments) were reviewed. Outcome was
      determined via analysis of race records, owner follow-up, and examination.
      RESULTS-Mean age of the horses was 3.1 years (range, 2 to 7 years), and time from
      injury to treatment ranged from 8 to 90 days. Mean +/- SD approximate lesion
      length on admission was 15.6 +/- 6.0 cm, and mean percentage cross-sectional area
      of the tendon affected was 26 +/- 18%. Twenty-six of the 40 horses underwent
      desmotomy of the accessory ligament of the SDF tendon. Echolucency was reduced in
      23 of 26 horses by the end of the treatment period. Twenty-one of 34 (62%) horses
      for which race data were available raced at least once after treatment, including
      10 (30%) horses that raced between 1 and 4 times and 11 horses (32%) that raced
      >= 5 times. Thirteen of 28 (46%) horses had a recurrence of tendonitis or
      developed tendonitis elsewhere. CONCLUSIONS AND CLINICAL RELEVANCE-Results
      suggested that in Thoroughbred racehorses with SDF tendonitis, intralesional
      injection of IGF-I led to a decrease in ultrasonographic lesion severity, but
      treated horses had only a moderate prognosis for return to racing.

PMID- 21961642
TI  - The inflammatory response in lungs of rats exposed on the airborne particles
      collected during different seasons in four European cities.
AB  - Epidemiological studies have reported associations of ambient particulate air
      pollution, especially particulate matter (PM) less than 10 MUm with exacerbations
      of asthma and chronic obstructive pulmonary disease. In an in vivo model, we have
      tested the toxicity of urban airborne particles collected during spring, summer,
      and winter seasons in four cities (Amsterdam, Lodz, Oslo, and Rome) spread across
      Europe. The seasonal differences in inflammatory responses were striking, and
      almost all the study parameters were affected by PM. Coarse fractions of the
      urban particle samples were less potent per unit mass than the fine fractions in
      increasing cytokine [macrophage inflammatory protein (MIP)-2 and tumor necrosis
      factor (TNF)-alpha] levels and in reducing Clara-cell secretory protein (CC16)
      levels. This study shows that PM collected at 4 contrasting sites across Europe
      and during different seasons have differences in toxic potency. These differences
      were even more prominent between the fine and coarse fractions of the PM.

PMID- 21961643
TI  - Impaired gas bladder inflation in zebrafish exposed to a novel heterocyclic
      brominated flame retardant tris(2,3-dibromopropyl) isocyanurate.
AB  - The teleost gas bladder is a gas-filled internal organ that processes gas
      exchange and controls buoyancy. Here we report that an emerging heterocyclic
      brominated flame retardant, tris(2,3-dibromopropyl) isocyanurate (TBC), causes
      defects in the inflation of the gas bladder of zebrafish larvae. This could cause
      impaired motility, which can ultimately lead to their death. Exposure to
      zebrafish embryos revealed that TBC had the most significant influence on the
      larvae at 72-96 h postfertilization, which coincided with the time that the gas
      bladder first inflates. Critical factors involved in early zebrafish gas bladder
      development remained at normal levels, which indicated that TBC caused defects in
      the inflation of the gas bladder without disrupting early organogenesis. However,
      the ultrastructure of the gas bladder was altered in the TBC-treated groups: the
      electron density of cytoplasmic vesicles was changed and the mitochondria were
      damaged. We deduce that TBC causes damage to mitochondria that influences the
      secretion of mucus-like material, resulting in defects in gas bladder inflation.
      For the first time, we report that the gas bladder could be a primary target
      organ for TBC, and assessment of the gas bladder should be included in toxicity
      testing protocols of zebrafish embryos.

PMID- 21961644
TI  - Single intraoperative intravenous Co-Amoxiclav versus postoperative full oral
      course in prevention of postadenotonsillectomy morbidity: a randomised clinical
      trial.
AB  - BACKGROUND: Adenotonsillectomy results in postoperative morbidity which
      otolaryngologists attempt to reduce by use of antibiotics. The regimes used as
      quite varied with some opting for a full oral course postoperatively while others
      prefer prophylactic doses. This randomised clinical trial done in Kenyatta
      National Hospital, Kenya had the aim of comparing the efficacy of Co-Amoxiclav
      given as a single intravenous dose with a full oral course in the prevention of
      post adenotonsillectomy morbidity. METHODS: 126 patients below 12 years scheduled
      to undergo adenotonsillectomy were randomised into two groups. 63 were given a
      single intravenous dose of Enhancin [Co-Amoxiclav] at induction while the
      remaining half received a five days oral course of the same postoperatively. All
      received oral Pacimol [Paracetamol] in the postoperative period. Analysis was
      done and comparison made between the two groups with regards to pain, fever and
      diet tolerated in the postoperative period with a follow up period of seven days.
      RESULTS: There was no statistical significant difference between the two groups
      with regards to postoperative pain, fever and diet tolerated. All had a P-value >
      0.2. Postoperative pain was highest in the first postoperative day and reduced
      progressively to the lowest level on the 7th postoperative day. As pain reduced,
      patients were able to tolerate a more solid diet with all but 6 tolerating their
      usual diet. 4 patients developed fever in the 1st postoperative day which did not
      progress to the next day. One patient had fever on the 4th and 7th postoperative
      day and was admitted in the paediatrics' ward with a chest infection. All these
      patients with history of fever were in the group that was on oral postoperative
      Co-Amoxiclav. CONCLUSION: A single intraoperative dose of Co-Amoxiclav given
      intravenously at induction was found to be just as effective as a full oral
      course of the same given postoperatively in the prevention of post
      adenotonsillectomy morbidity. The prophylactic dose is favoured over the later as
      it is cheaper, ensures compliance and relieves off the need for refrigeration of
      the oral suspension as not all have access to refrigeration in low economy
      countries as ours. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01267942.

PMID- 21961645
TI  - Bioavailability and pharmacokinetics of S-propargyl-L-cysteine, a novel
      cardioprotective agent, after single and multiple doses in Beagle dogs.
AB  - As a novel hydrogen sulfide-modulated agent, S-propargyl-L-cysteine (SPRC) is
      proven to be a potent cardioprotective candidate. Bioavailability and
      pharmacokinetics of SPRC (20 mg/kg) in beagle dogs after oral and intravenous
      administrations were investigated in this study. Plasma concentrations of SPRC
      were measured by a LC-MS/MS method. Intravenous administration of SPRC (single
      dose) to beagle dogs gave a mean plasma half-life of 14.7 h, mean clearance of
      0.4 ml min-1 kg-1 and mean apparent volume of distribution of 0.56 L/kg. Single
      oral administration was completely, fast absorbed (T(max)= 0.33 +/- 0.20 h) with
      a mean absolute availability of 112% and mean plasma half-life of 16.5 h.
      Multiple oral administration (once daily for 10 consecutive days) of SPRC to dogs
      resulted in steady state plasma drug concentration being reached after seven
      doses and didn't cause obvious accumulation. No significant difference was found
      between the single and multiple pharmacokinetic parameters.

PMID- 21961646
TI  - Effect of the simultaneous interaction among ascorbic acid, iron and pH on the
      oxidative stability of oil-in-water emulsions.
AB  - The objective of this study was to demonstrate how different factors can
      simultaneously influence the oxidative stability of an oil-in-water emulsion, and
      how these factors can be used to enlarge the variation range of oxidation
      markers, expressed as peroxide value (PV) and TBARS. Initially, a Plackett-Burman
      design was used to screen seven factors (temperature, pH, and iron, copper,
      ascorbyl palmitate, ascorbic acid, and sodium chloride concentrations). A
      temperature elevation of 30 to 60  degrees C reduced PV and TBARS, a pH change
      from 3.0 to 7.0 increased PV and reduced TBARS, and the presence of ascorbic acid
      (1 mmol/L) had no significant effect on PV but increased TBARS (p < 0.05). Thus,
      the temperature was fixed at 30  degrees C, and an emulsion was formulated with
      different combinations of ascorbic acid, iron, and pH according to a central
      composite rotatable design. Regression models were fitted to PV and TBARs
      responses and optimized to get the higher values of both markers of oxidation.
      The optimized emulsion contained 1.70 mmol/L AH (ascorbic acid) and 0.885 mmol/L
      FeSO(4) . 7H(2)O (1.0 mmol/L Fe(2+)) at pH 5.51 and 30  degrees C. The range of
      variation observed for oxidation markers in the optimized emulsion model (PV, 0
      4.27 mequiv/L; TBARS, 0-13.55 mmol/L) was larger than the variation observed in
      the nonoptimized model (PV, 0-1.05 mequiv/L; TBARS, 0-1.00 mmol/L). The
      antioxidant activity of six compounds (Trolox, alpha-tocopherol, caffeic acid,
      gallic acid, catechin, and TBHQ) was evaluated using the optimized emulsion
      conditions. After application of the Tukey HSD post hoc statistical test, the
      samples that were not different (p < 0.05) in the nonoptimized emulsions showed a
      significant difference in the optimized emulsions. Considering the importance of
      the interactions on oxidation studies, our model represents a significant
      improvement in a direct methodology that can be applied to evaluate natural
      compounds under different combination of factors.

PMID- 21961647
TI  - Kinetic, mechanistic, and structural modeling studies of truncated wild-type
      leucine-rich repeat kinase 2 and the G2019S mutant.
AB  - Leucine-rich repeat kinase 2 (LRRK2), a large and complex protein that possesses
      two enzymatic properties, kinase and GTPase, is one of the major genetic factors
      in Parkinson's disease (PD). Here, we characterize the kinetic and catalytic
      mechanisms of truncated wild-type (t-wt) LRRK2 and its most common mutant, G2019S
      (t-G2019S), with a structural interpretation of the kinase domain. First, the
      substitution of threonine with serine in the LRRKtide peptide results in a much
      less efficient substrate as demonstrated by a 26-fold decrease in k(cat) and a 6
      fold decrease in binding affinity. The significant decrease in k(cat) is
      attributed to a slow chemical transfer step as evidenced by the inverse solvent
      kinetic isotope effect in the proton inventory and pL (pH or pD)-dependent
      studies. The shape of the proton inventory and pL profile clearly signals the
      involvement of a general base (pK(a) = 7.5) in the catalysis with a low
      fractionation factor in the ground state. We report for the first time that the
      increased kinase activity of the G2019S mutant is substrate-dependent. Homology
      modeling of the kinase domain (open and closed forms) and structural analysis of
      the docked peptide substrates suggest that electrostatic interactions play an
      important role in substrate recognition, which is affected by G2019S and may
      directly influence the kinetic properties of the enzyme. Finally, the GTPase
      activity of the t-G2019S mutant was characterized, and the mutation modestly
      decreases GTPase activity without significantly affecting GTP binding affinity.

PMID- 21961648
TI  - No small matter: qualitatively distinct challenges of pediatric genomic studies.

PMID- 21961649
TI  - Antiobesity activity of fermented Angelicae gigantis by high fat diet-induced
      obese rats.
AB  - This study aimed to evaluate the effects of Monascus purpureus-fermented
      Angelicae gigantis Radix (FAG) on body weight gain, visceral fat accumulation,
      biochemical markers of obesity, and the mRNA expression levels of various genes
      involved in adipogenesis in a high-fat-diet (HFD)-induced rat model of obesity.
      Effect of nodakenin isolated from Angelicae gigantis on 3T3-L1 preadipocyte
      differentiation was also investigated in vitro. Male Sprague-Dawley rats were
      randomly divided into five groups (n = 6 per group) based on five dietary
      categories: HFD control, HFD + 2.5% (w/w) AG, HFD + 5% AG, HFD + 2.5% FAG, and
      HFD + 5% FAG. Present study investigated nodakenin isolated from AG and FAG roots
      by measuring fat accumulation in 3T3-L1 preadipocyte using Oil Red O staining.
      FAG administration effectively lowered the body weight gain, visceral fat
      accumulation, and hepatic and serum lipid and leptin concentrations in obese
      rats. In addition, FAG administration significantly reduced the mRNA expression
      levels of adipose tissue genes encoding adipocyte protein 2 (aP2), peroxisome
      proliferator-activated receptor gamma 2 (PPARgamma2), and CCAT/enhancer-binding
      protein alpha (C/EBPalpha) as compared with HFD group. Furthermore, nodakenin
      reduced the fat accumulation in differentiated 3T3-L1 adipocytes in a dose
      dependent manner. FAG ameliorates HFD-induced obesity, probably by modulating
      multiple genes associated with adipogenesis in the visceral fat tissue of rats.
      Accordingly, fermented Angelicae gigantis may be an ideal candidate for obesity
      relief.

PMID- 21961650
TI  - Evidence for association of an ACCN1 gene variant with response to lithium
      treatment in Sardinian patients with bipolar disorder.
AB  - AIMS: Bipolar disorder (BD) is a lifelong psychiatric illness characterized by
      manic and depressive episodes affecting 1-5% of the general population. Among
      mood-stabilizing treatments, lithium represents the mainstay in the therapeutic
      management of BD. However, besides the relatively high rate of excellent
      responders, a significant fraction of patients present patterns of partial or
      nonresponse to lithium. This variability might be influenced by genetic factors,
      even though findings have so far been inconclusive. Here, we present the results
      of an exploratory genome-wide scan followed by extended genotyping carried out on
      a sample of 204 Sardinian BD patients characterized for lithium response.
      MATERIALS & METHODS: Phenotypic assessment of lithium response was made using the
      retrospective criteria of long-term treatment response scale. Using
      Affymetrix((r)) 6.0 SNP arrays, we genotyped a subsample of 52 BD patients evenly
      distributed at the extreme ends of the treatment response scale. The associated
      SNPs were then prioritized and selected for validation and extended genotyping in
      the whole sample of BD patients characterized for lithium response. Association
      was also tested using the scale for a quantitative trait analysis. RESULTS: Our
      findings showed that several SNPs were nominally associated (p <= 10(-5)) with
      lithium response in the subgroup of 52 BD subjects. Some association signals were
      then confirmed in the extended sample. The strongest association, also supported
      by the quantitative trait analysis, was shown for a SNP located in intron 1 of
      the ACCN1 gene, encoding for a cation channel with high affinity for sodium and
      permeable to lithium. CONCLUSION: Our results indicate that ACCN1 gene is a
      potential candidate for response to lithium treatment that would serve as a
      genetic marker of lithium efficacy for BD patients.

PMID- 21961651
TI  - SULT1A1, CYP2C19 and disease-free survival in early breast cancer patients
      receiving tamoxifen.
AB  - AIM: Tamoxifen biotransformation to endoxifen, a potent antiestrogen, is
      catalyzed by CYP2D6. In addition, CYP2C19 and SULT1A1 have also been implicated
      in the metabolism of tamoxifen. We sought to evaluate the importance of SULT1A1
      copy number and CYP2C19*17 on disease-free survival (DFS) in postmenopausal women
      randomized to tamoxifen monotherapy in North Central Cancer Treatment Group 89-30
      52 from January 1991 to April 1995. MATERIALS & METHODS: We extracted DNA from
      paraffin-embedded tumors and determined tumor SULT1A1 copy number and CYP2C19*17
      genotype. The association of genotype with DFS was determined using the log-rank
      test. Multivariate cox modeling was performed using traditional prognostic
      factors, as well as CYP2D6 genotype. SULT1A1 copy number and CYP2C19*17 genotype
      was determined in 190 out of 256 patients (95% Caucasian). RESULTS: The median
      follow-up for living patients was 14 years. DFS did not differ according to
      SULT1A1 copy number (p = 0.482) or CYP2C19*17 genotype (p = 0.667). Neither
      SULT1A1 copy number or CYP2C19*17 genotype was associated with disease recurrence
      in this cohort. CONCLUSION: Future studies are needed to identify whether other
      genetic and environmental factors which affect tamoxifen metabolism are
      associated with tamoxifen clinical outcomes.

PMID- 21961652
TI  - The utility of naphthyl-keratin adducts as biomarkers for jet-fuel exposure.
AB  - We investigated the association between biomarkers of dermal exposure, naphthyl
      keratin adducts (NKA), and urine naphthalene biomarker levels in 105 workers
      routinely exposed to jet-fuel. A moderate correlation was observed between NKA
      and urine naphthalene levels (p = 0.061). The NKA, post-exposure breath
      naphthalene, and male gender were associated with an increase, while CYP2E1*6 DD
      and GSTT1-plus (++/+-) genotypes were associated with a decrease in urine
      naphthalene level (p < 0.0001). The NKA show great promise as biomarkers for
      dermal exposure to naphthalene. Further studies are warranted to characterize the
      relationship between NKA, other exposure biomarkers, and/or biomarkers of
      biological effects due to naphthalene and/or PAH exposure.

PMID- 21961654
TI  - Integration of public health into medical education: an introduction to the
      supplement.

PMID- 21961653
TI  - The combination of gefitinib and RAD001 inhibits growth of HER2 overexpressing
      breast cancer cells and tumors irrespective of trastuzumab sensitivity.
AB  - BACKGROUND: HER2-positive breast cancers exhibit high rates of innate and
      acquired resistance to trastuzumab (TZ), a HER2-directed antibody used as a first
      line treatment for this disease. TZ resistance may in part be mediated by
      frequent co-expression of EGFR and by sustained activation of the mammalian
      target of rapamycin (mTOR) pathway. Here, we assessed feasibility of combining
      the EGFR inhibitor gefitinib and the mTOR inhibitor everolimus (RAD001) for
      treating HER2 overexpressing breast cancers with different sensitivity to TZ.
      METHODS: The gefitinib and RAD001 combination was broadly evaluated in TZ
      sensitive (SKBR3 and MCF7-HER2) and TZ resistant (JIMT-1) breast cancer models.
      The effects on cell growth were measured in cell based assays using the fixed
      molar ratio design and the median effect principle. In vivo studies were
      performed in Rag2M mice bearing established tumors. Analysis of cell cycle,
      changes in targeted signaling pathways and tumor characteristics were conducted
      to assess gefitinib and RAD001 interactions. RESULTS: The gefitinib and RAD001
      combination inhibited cell growth in vitro in a synergistic fashion as defined by
      the Chou and Talalay median effect principle and increased tumor xenograft growth
      delay. The improvement in therapeutic efficacy by the combination was associated
      in vitro with cell line dependent increases in cytotoxicity and cytostasis while
      treatment in vivo promoted cytostasis. The most striking and consistent
      therapeutic effect of the combination was increased inhibition of the mTOR
      pathway (in vitro and in vivo) and EGFR signaling in vivo relative to the single
      drugs. CONCLUSIONS: The gefitinib and RAD001 combination provides effective
      control over growth of HER2 overexpressing cells and tumors irrespective of the
      TZ sensitivity status.

PMID- 21961655
TI  - Public health and medicine where: the twain shall meet.

PMID- 21961656
TI  - Principles for authentic population health.

PMID- 21961657
TI  - Exploring the context: contemporary public health.

PMID- 21961658
TI  - Exploring the context: contemporary medical education.

PMID- 21961660
TI  - Overcoming challenges to integrating public and population health into medical
      curricula.
AB  - Integrating public health into medical curricula poses a substantial challenge to
      educators. However, the needs of trainees and the population requirements of
      accrediting bodies provide a compelling call to action to improve how tomorrow's
      medical practitioners are prepared to incorporate public health into their
      practices. This article provides insights about the nature of the challenges, and
      it identifies opportunities and practical approaches to integrating public health
      content into medical school curricula. The paper incorporates authors' opinions
      with a synthesis of the discussions from a workshop at the 2010 "Patients and
      Populations: Public Health in Medical Education" conference.

PMID- 21961659
TI  - Refocusing knowledge generation, application, and education: raising our gaze to
      promote health across boundaries.

PMID- 21961661
TI  - Integration of community health teaching in the undergraduate medicine curriculum
      at the University of Toronto.
AB  - BACKGROUND: In 1999, Determinants of Community Health was introduced at the
      Faculty of Medicine, University of Toronto. The course spanned all 4 years of the
      undergraduate curriculum and focused on addressing individual patient and
      community needs, prevention and population health, and diverse learning contexts.
      PURPOSE: To demonstrate the value of an integrated, longitudinal approach to the
      efficiency of delivering a public health curriculum. DESIGN: Time-series
      comparing the curricular change over two periods of time. SETTING/PARTICIPANTS:
      Undergraduate medical students from 1993 to 2009. INTERVENTION: Using a spiral
      curriculum, the educational materials are integrated across all 4 years, based on
      the concept of medical decision making in a community context. MAIN OUTCOME
      MEASURES: This study compares measures of student satisfaction and national
      rankings of the University of Toronto with the other 16 Canadian medical schools
      for the "Population Health, Ethical, Legal, and Organizational aspects of the
      practice of medicine" component of the Medical Council of Canada Qualifying
      Examination Part 1. RESULTS: The University of Toronto has been ranked either
      first or second place nationally, in comparison to lower rankings in previous
      years (p<0.02 on the Kruskal-Wallis test). Student ratings indicated the course
      was comparable to others in the curriculum. CONCLUSIONS: For the same amount of
      curricular time, an integrated spiral curriculum for teaching public health
      appears to be more effective than traditional approaches.

PMID- 21961662
TI  - Using clinical skills exams to evaluate medical student skills in prevention.
AB  - BACKGROUND: In 2006, the Brody School of Medicine Regional Medicine-Public Health
      Education Center integrated the teaching of prevention into the curriculum for
      first-, second-, and third-year medical students. PURPOSE: The purpose of this
      article is to report on the use of clinical skills exams (CSEs) in the evaluation
      of prevention health instruction for the period 2006-2010. METHODS: Two CSEs were
      employed to measure preventive skills at the end of the third year of medical
      school. CSE-1 was a woman aged 56 years with knee pain. The outcome measure is
      the percentage of students asking three or more prevention history items. CSE-2
      was a boy, aged 15 years, undergoing a sports physical/preventive screening. The
      outcome measure is the number of prevention items queried. RESULTS: For CSE-1,
      the percentage of students who met the outcome measure increased to 83% in 2010
      as compared to 62% in both 2009 and 2007. The improvement between 2007 and 2010
      was significant with a p=0.0080 (Fisher's exact test). Of the 64 students taking
      the third-year medical student objective structured clinical examination-2 in
      June 2009, the greatest number queried the following preventive items: exercise
      (98%), alcohol misuse (98%), drug use (98%), school and grades (98%), sexual
      activity (98%), and tobacco use (97%). CONCLUSIONS: By integrating prevention
      elements into CSE cases, the results are useful for student assessment and may be
      a powerful influence on curricular design, leading to an increase in prevention
      content.

PMID- 21961663
TI  - Integrative cases for preclinical medical students: connecting clinical, basic
      science, and public health approaches.
AB  - BACKGROUND: Healthcare and public health systems are each transforming, resulting
      in a need for better integration between clinical and population-based approaches
      to improve the health of populations. These changes also demand substantial
      transformations in the curriculum for medical students. Integrative Cases were
      designed for all first- and second-year medical students to provide them with
      more awareness, knowledge, and skills in integrating public health into clinical
      medicine. Each case examines basic science factors, clinical approaches, and
      public health determinants, including risk factors and direct and indirect
      contributing factors. PURPOSE: This study was designed to evaluate the
      effectiveness of Integrative Cases in the medical student curriculum. METHODS:
      Integrative Cases were formatively evaluated using standardized online post-event
      questionnaires emailed to students after each case. The questionnaires focused on
      goals specific to each case, ratings of particular sessions and facilitators,
      general impressions of the case, and student suggestions for improvement.
      RESULTS: Student evaluations indicate that Integrative Cases achieved their
      goals, especially providing experiences that offer a more expansive view of
      medicine and public health, stimulating interest and questions that anticipate
      future learning and making connections across basic science, medicine, and
      health. Students also indicated that these cases added to their understanding of
      public health issues and how to apply what they had learned to patient care.
      CONCLUSIONS: Integrative Cases demonstrate the effectiveness of a comprehensive
      approach that integrates clinical medicine with basic science and public health
      perspectives.

PMID- 21961664
TI  - Planning and incorporating public health preparedness into the medical
      curriculum.
AB  - As part of a 2010 conference entitled "Patients and Populations: Public Health in
      Medical Education," faculty from four U.S. medical schools (Case Western Reserve
      University, Harvard Medical School, the University of Colorado School of
      Medicine, and the University of Vermont College of Medicine), collaborated on a
      workshop to help other medical educators develop scenario-based learning
      experiences as practical, engaging, and effective mechanisms for teaching public
      health principles to medical school students. This paper describes and compares
      four different medical schools' experiences using a similar pandemic exercise
      scenario, discusses lessons learned, and suggests a curricular framework for
      medical schools adding such exercises to their population health curriculum.
      Different strategies to create realistic scenarios and engage students, including
      use of professionals and stakeholders from the community, are described.

PMID- 21961665
TI  - A fourth-year medical school rotation in quality, patient safety, and population
      medicine.
AB  - BACKGROUND: Quality improvement and population medicine are skills that are
      increasingly important for physicians to possess. Methods to achieve foundational
      acquisition of these skills in medical school have not been well described in the
      past. PURPOSE: The primary goal of this project is to provide hands-on,
      experiential learning in full-cycle population-based care. METHODS: A description
      is given of a 4-week, team-based, rapid-cycle quality improvement project
      embedded in a required fourth-year medical school rotation. Over the course of 4
      years a nonspecialty generic Ambulatory Care rotation was converted to a
      population-based learning rotation. For the last 3 years this rotation has
      required students to participate in teams of three to four students to assess,
      plan, implement, and evaluate a quality improvement project. RESULTS: Between
      2008 and 2010 a total of 510 students completed the rotation. During this time
      the project component of the rotation received a 53% average rating of
      "excellent" or "above average." Qualitative evaluation indicates the project to
      be an acceptable and worthwhile educational experience for medical students,
      adding new insights and occasionally career-changing perspectives. CONCLUSIONS:
      Although experiential team-based quality improvement projects are a new format
      for learning in the medical school environment, it can be implemented in a format
      that is acceptable and beneficial to future physicians and healthcare systems.

PMID- 21961666
TI  - Community-academic partnerships: how can communities benefit?
AB  - In answer to the question of how academic institutions will meet medical
      education needs and public health challenges of the 21st century, a strong,
      vibrant, and sustained community partnership has been developed to teach public
      health, address community public health needs, and develop health policy to
      sustain these improvements, all with a practical approach. In this paper, the
      partnership between the University of Vermont College of Medicine and various
      community agencies is described from the perspective of how the community can
      benefit from educational efforts in public health. Particular focus is given to
      the community-academic partnership model in public health, a strong and sustained
      partnership between the University of Vermont College of Medicine and the United
      Way of Chittenden County Volunteer Center that began in 2004. Public health
      projects are designed, through partnerships with community nonprofit agencies, to
      be effective in addressing community issues while helping prepare students to
      become problem-solvers in population health. Examples of benefits seen by the
      community are used to illustrate the success of this approach. Project examples
      and a brief case study illustrate how community-academic partnerships in medical
      education can serve as a "catalyst" to improving community health.

PMID- 21961667
TI  - Reuniting public health and medicine: the University of New Mexico School of
      Medicine Public Health Certificate.
AB  - The University of New Mexico School of Medicine (UNMSOM) sought to train medical
      students in public health concepts, knowledge, and skills as a means of improving
      the health of communities statewide. Faculty members from every UNMSOM department
      collaborated to create and integrate a public health focus into all years of the
      medical school curriculum. They identified key competencies and developed new
      courses that would synchronize students' learning public health subjects with the
      mainstream medical school content. New courses include: Health Equity: Principles
      of Public Health; Epidemiology and Biostatistics; Evidence-Based Practice;
      Community-Based Service Learning; and Ethics in Public Health. Students
      experiencing the new courses, first in pilot and then final forms, gave high
      quantitative ratings to all courses. Some students' qualitative comments suggest
      that the Public Health Certificate has had a profound transformative effect.
      Instituting the integrated Public Health Certificate at UNMSOM places it among
      the first medical schools to require all its medical students to complete medical
      school with public health training. The new UNMSOM Public Health Certificate
      courses reunite medicine and public health in a unified curriculum.

PMID- 21961668
TI  - Public health and medical education: a natural alliance for a new regional
      medical school.
AB  - A century ago, the Flexner Report challenged U.S. medical schools to critically
      evaluate their curricula in order to nurture physicians equipped to meet the
      needs of an evolving society. Recently, medical educators have been charged to
      increase the emphasis on prevention, care of populations, public health, and
      community medicine. The Commonwealth Medical College (TCMC) is a new MD-granting
      medical school inspired by and founded in response to a community need. The
      founders' vision was to recruit and train physicians to fill workforce needs in
      Northeast Pennsylvania. In its first few years, TCMC embarked on two major public
      health initiatives, the Regional Health Assessment and the Community Health
      Research Projects (CHRPs). The results of the health assessment have been used to
      guide TCMC's curricular development and research agenda. The CHRPs foster
      commitment to community involvement, regional engagement, and participatory
      research. TCMC partners with various organizations and community physicians to
      ensure that students learn (1) to apply knowledge and skills acquired through the
      course of their studies to public health research in varied settings; (2) the
      fundamentals of community engagement, collaboration, and service-based practice;
      and (3) to address the different needs of patient subgroups and populations.
      These programs provide opportunities for students to be active participants in
      community capacity building while achieving specific competencies in public
      health. Existing partnerships with community organizations are enhanced,
      strengthening the regional focus of the school. This model of incorporating
      public health into medical education can potentially be replicated in other
      institutions in the U.S. and internationally.

PMID- 21961669
TI  - The urban and community health pathway: preparing socially responsive physicians
      through community-engaged learning.
AB  - One of five options for the new required Medical College of Wisconsin Pathways
      program, the Urban and Community Health Pathway (UCHP), links training with
      community needs and assets to prepare students with the knowledge, skills, and
      attitudes to provide effective care in urban, underserved settings; promote
      community health; and reduce health disparities. Students spend at least 10 hours
      per month on pathway activities: 4 hours of core material delivered through
      readings, didactics, case discussions, and site visits; and at least 6 hours of
      experiential noncore activities applying core competencies, guided by an
      Individualized Learning Plan and faculty advisor. Noncore activities include
      community-engaged research, service-learning activities or other relevant
      experiences, and submission of a synthesis paper addressing pathway competencies.
      The first cohort of students began their pathways in January 2010. Of 560
      participating students, 95 (of which 48 were first-year, 21 second-year, and 26
      third-year students) selected UCHP. Core sessions focused on public health,
      social determinants, cultural humility, poverty, the local healthcare system, and
      safety net. During noncore time, students engaged in projects addressing
      homelessness, obesity, advocacy, Hmong and Latino health, HIV, asthma, and
      violence prevention. Students enjoyed working with peers across classes and
      favored interactive, community-based sessions over didactics in the classroom.
      Students' papers reflected a range of service and scholarly activities and a
      deepened appreciation of social and economic influences on health. The UCHP
      enriches the traditional curriculum with individualized, community-based
      experiences to build knowledge about health determinants and skills in partnering
      with communities to improve health.

PMID- 21961670
TI  - Public Health Area of Concentration: a model for integration into medical school
      curricula.
AB  - Calls for more public health education for medical students date back at least
      150 years. In recent years, medical schools have increased their required
      coursework in core public health topics such as epidemiology, biostatistics, and
      behavioral determinants of health. Some schools have created more in-depth
      alternatives, including combined or concurrent master's degrees; MD/PhD programs
      with a public health track; certificates in public health; or complete re
      envisioning of the school into an integrated medical and public health
      institution. In 2009 the University of Pittsburgh School of Medicine began a
      Public Health Area of Concentration (AOC) that provides an optional, integrated
      curriculum that includes key elements of research, practice, and leadership. The
      AOC is a partnership between two schools at the University of Pittsburgh-
      Medicine and Public Health--and the local county health department. The result is
      a program that provides mentorship and training over 4 years of education
      designed to mend the long historical divide between the skills and constituencies
      of individual and population health. In addition, the AOC is relatively easy and
      inexpensive to implement and is modular in nature. The Public Health AOC is a
      simple model for incorporating many key aspects of public health into medical
      education and can be duplicated by any university that is willing to create
      partnerships and work across boundaries.

PMID- 21961671
TI  - Public health education for emergency medicine residents.
AB  - Emergency medicine (EM) has an important role in public health, but the ideal
      approach for teaching public health to EM residents is unclear. As part of the
      national Regional Public Health-Medicine Education Centers-Graduate Medical
      Education initiative from the CDC and the American Association of Medical
      Colleges, three EM programs received funding to create public health curricula
      for EM residents. Curricula approaches varied by residency. One program used a
      modular, integrative approach to combine public health and EM clinical topics
      during usual residency didactics, one partnered with local public health
      organizations to provide real-world experiences for residents, and one drew on
      existing national as well as departmental resources to seamlessly integrate more
      public health-oriented educational activities within the existing residency
      curriculum. The modular and integrative approaches appeared to have a positive
      impact on resident attitudes toward public health, and a majority of EM residents
      at that program believed public health training is important. Reliance on pre
      existing community partnerships facilitated development of public health
      rotations for residents. External funding for these efforts was critical to their
      success, given the time and financial restraints on residency programs. The
      optimal approach for public health education for EM residents has not been
      defined.

PMID- 21961672
TI  - Identifying public health competencies relevant to family medicine.
AB  - Public health situations faced by family physicians and other primary care
      practitioners, such as severe acute respiratory syndrome (SARS) and more recently
      H1N1, have resulted in an increased interest to identify the public health
      competencies relevant to family medicine. At present there is no agreed-on set of
      public health competencies delineating the knowledge and skills that family
      physicians should possess to effectively face diverse public health challenges.
      Using a multi-staged, iterative process that included a detailed literature
      review, the authors developed a set of public health competencies relevant to
      primary care, identifying competencies relevant across four levels, from "post
      MD" to "enhanced." Feedback from family medicine and public health educator
      practitioners regarding the set of proposed "essential" competencies indicated
      the need for a more limited, feasible set of "priority" areas to be highlighted
      during residency training. This focused set of public health competencies has
      begun to guide relevant components of the University of Toronto's Family Medicine
      Residency Program curriculum, including academic half-days; clinical experiences,
      especially identifying "teachable moments" during patient encounters; resident
      academic projects; and elective public health agency placements. These
      competencies will also be used to guide the development of a family medicine
      public health primer and faculty development sessions to support family medicine
      faculty facilitating residents to achieve these competencies. Once more fully
      implemented, an evaluation will be initiated to determine the degree to which
      these public health competencies are being achieved by family medicine graduates,
      especially whether they attained the knowledge, skills, and confidence necessary
      to effectively face diverse public health situations-from common to emergent.

PMID- 21961673
TI  - Weaving public health education into the fabric of a family medicine residency.
AB  - Policymakers and accrediting bodies have recognized the importance of integrating
      public health, population health, and prevention into graduate medical education
      programs. The high prevalence of chronic illness, coupled with the impact of
      behavioral and societal determinants of health, necessitate an urgent call for
      family medicine residencies to prepare future leaders to meet these challenges.
      The University of Massachusetts Worcester Family Medicine Residency recently
      developed an integrated curriculum that strives to develop a culture of
      incorporating fundamental public health principles into everyday practice. This
      public health curriculum was designed to integrate new topics within the current
      residency structure through longitudinal and concentrated experiences. This
      strategy has substantially improved public health and prevention education
      without substantial impact on the already strained residency curricular
      structure. This paper describes the integration of public health and prevention
      education into a family medicine residency to help residents acquire the
      fundamental skills necessary to improve a population's health.

PMID- 21961674
TI  - A curriculum in health systems and public health for internal medicine residents.
AB  - BACKGROUND: Medical educators and accreditation organizations recognize that
      healthcare professionals in the future will depend on working knowledge of the
      larger contexts and systems of health care, including population and public
      health. Little published guidance on medical education in health systems and
      public health exists, particularly for graduate medical education. PURPOSE: This
      study describes the evaluation of a curriculum in health systems and public
      health which was successfully implemented in an internal medicine residency
      training program. DESIGN: A pilot program consisting of a week-long didactic
      curriculum for senior residents, including ten half-day seminars. Two cycles of
      the pilot curriculum were implemented in September and November, 2007.
      SETTING/PARTICIPANTS: The participants were third-year residents in an internal
      medicine training program at a large, urban academic medical center.
      INTERVENTION: The 1-week curriculum was fully implemented and evaluated in the
      academic years 2008-2010. It included seminars on health policy and economics,
      health insurance, technology and cost assessment, legal medicine, public health,
      community-oriented primary care, and local health department initiatives. MAIN
      OUTCOME MEASURES: Residents evaluated the quality and impact of the seminars and
      overall curriculum, retrospectively assessed their knowledge of topics presented
      before and after the seminars, and rated the seminars that were most valuable to
      them. RESULTS: The seminars were highly rated by the participating residents, and
      the curriculum was judged by them to be valuable in their clinical activities and
      professional development. CONCLUSIONS: Key lessons learned included the
      importance of accessing resources external to the residency program and the
      challenge of making learning in health systems and public health active and
      relevant to clinical practice.

PMID- 21961675
TI  - Community health training for internal medicine residents working with community
      partners.
AB  - Graduate and undergraduate medical training are incorporating public health
      curricula into their programs to enable future physicians to participate in
      public health activities and improve the health of the communities. This paper
      highlights two approaches to a community health curriculum implemented at the
      Cambridge Health Alliance Internal Medicine Training Program from 2008-2010.
      Between 2008 and 2009, the residency program incorporated a longitudinal
      curriculum for first-year residents. The goal of the curriculum was to expose
      residents to basic community health research models while giving them time to
      participate in a 1-year practicum with the Cambridge Public Health Department.
      Strengths included increasing resident knowledge about the local public health
      department and providing residents with an opportunity to work with staff and
      patients in that setting. Limitations of such a design included staff time
      constraints for coordinating with community partners as well as resident
      dissatisfaction with being involved in only select portions of an evolving
      project. This curriculum was therefore revised into a 1-month ambulatory block
      consisting of didactics and a practicum with the local YWCA in September 2010.
      Residents felt that this design yielded more time in didactics than in the
      practicum. Both designs offer important learning points in terms of practically
      incorporating public health activities in a tightly scheduled residency-training
      program. The current paper highlights the importance of partnering with a
      community organization such as a public health department or the YWCA. Emphasis
      is placed on the contributions that residents can make to these organizations
      while they learn how to integrate clinical and community health activities.

PMID- 21961676
TI  - Integrating population health into a general surgical residency curriculum.
AB  - The once disparate fields of public health and medicine are slowly converging and
      reintegrating. Public health principles of community interventions and
      partnerships to effect better population health are included in the curricula of
      more medical schools. For graduate medical education, the specialties of internal
      medicine, family medicine, and preventive medicine are intuitively obvious
      population health partners, whereas surgeons have been relatively silent in this
      area. Despite the fact that many common surgical diseases are directly
      attributable to preventable causes, including cancer, trauma, and obesity,
      surgical residents receive little formal population health education. However,
      surgeons have always been and are increasingly active within the public health
      sphere. Examples of surgical population health initiatives include trauma systems
      development and improvement, research on disparities, and global health
      initiatives, including disaster relief. This article describes a single
      institution experience utilizing modest curriculum changes, increased global
      health opportunities, and direct service learning to help integrate population
      health principles into a general surgical residency program.

PMID- 21961677
TI  - Faith-based partnerships in graduate medical education: the experience of the
      Morehouse School of Medicine Public Health/Preventive Medicine Residency Program.
AB  - Faith-based organizations can be strategic partners in addressing the needs of
      low-income and underserved individuals and communities. The Morehouse School of
      Medicine (MSM) Public Health/Preventive Medicine Residency Program (PH/PMR)
      collaborates with faith-based organizations for the purpose of resident
      education, community engagement, and service. These partners provide guidance for
      the program's community initiatives and health promotion activities designed to
      address health inequities. Residents complete a longitudinal community practicum
      experience with a faith-based organization over the 2-year training period.
      Residents conduct a community health needs assessment at the organization and
      design a health intervention that addresses the identified needs. The faith-based
      community practicum also serves as a vehicle for achieving skills in all eight
      domains of the Public Health Competencies developed by the Council on Linkages
      and all six Accreditation Council for Graduate Medical Education (ACGME) Core
      Competencies. The MSM PH/PMR Program has engaged in faith-based partnerships for
      7 years. This article discusses the structure of these partnerships, how partners
      are identified, funding sources for supporting resident projects, and examples of
      resident health needs assessment and intervention activities. The MSM PH/PMR
      Program may serve as a model to other residency and fellowship programs that may
      have an interest in developing partnerships with faith-based organizations.

PMID- 21961678
TI  - Role of preventive medicine residencies in medical education: a national survey.
AB  - BACKGROUND: In an era of substantial reform to the nation's health system, there
      has never been a greater need for physicians to understand public health. One way
      to foster public health in medical education is to utilize the resources within
      General Preventive Medicine and Public Health (PM) residency programs. Trained in
      public health and clinical medicine, PM physicians are uniquely positioned to
      bridge these disciplines. PURPOSE: Little is known about the level of engagement
      of PM residency programs in medical education. This study explores the current
      state of their involvement. METHODS: Program directors from all Accreditation
      Council for Graduate Medical Education-accredited PM residency programs were
      asked to participate in a survey to assess involvement in medical student and non
      PM resident education, including on nine key engagement criteria covering
      teaching, rotations, career interest groups, and other activities. The study was
      conducted and data analyzed in 2010. RESULTS: Thirty-five of 38 (92%) programs
      responded. Seventy-four percent reported that PM faculty taught medical students,
      and 34% taught at non-PM residency programs. The lowest level of engagement was
      seen in PM residents teaching non-PM residents (12%). Over half of all programs
      met four or fewer of the nine criteria. The most common barriers to engagement
      were lack of funding (53%) and lack of time (50%). CONCLUSIONS: These results
      suggest that PM residency programs are an underutilized resource in fostering
      public health in medical education, especially on engagement at the level of
      graduate medical education. Strategies to improve engagement should consider the
      nine criteria outlined in this study, as well as common barriers.

PMID- 21961679
TI  - Integrating environmental health into medical education.
AB  - Although environmental factors contribute to more than 25% of all global disease,
      and toxic agents ranked fifth in underlying causes of U.S. deaths in 2000,
      environmental medicine education is largely omitted in the continuum of U.S.
      medical education. The paucity of specialists trained in environmental medicine
      (i.e., occupational medicine and other preventive medicine specialties and
      subspecialties), coupled with the lack of adequate general medical education on
      how to prevent, diagnose, refer, or treat patients exposed to hazardous
      substances in the environment, contributes to lost opportunities for primary
      prevention or early intervention to mitigate or minimize environmentally related
      disease burden. Survey findings of graduating medical students over the past few
      years have identified environmental health as a medical school topic area that
      can be improved. This article reflects a panel presentation on the challenge of
      including environmental health in general medical education. It was given at the
      2010 "Patients and Populations: Public Health in Medical Education" conference
      cosponsored by the CDC and the American Association of Medical Colleges. A
      variety of educational strategies, models, and educational resources are
      presented that illustrate how recommended competency-based environmental health
      content can be integrated into medical education to better prepare medical
      students and physicians without specialized expertise in environmental medicine
      to provide or facilitate environmental preventive or curative patient care.

PMID- 21961680
TI  - A primer on population health: a new resource for students and clinicians.
AB  - This is one of six short papers that describe additional innovations that support
      the integration of public health into medical education. These were featured in
      the "Patients and Populations: Public Health in Medical Education" conference and
      describe innovative endeavors or curricular components not previously published.
      This paper describes the Association of Faculties of Medicine of Canada's Primer
      in Population Health and its collaborative development with contributions from
      all Canadian medical schools, in particular from the medical faculties of the
      University of Ottawa and the Universite de Sherbrooke. Although evaluation data
      will not be available until the primer has been in use for at least 1 year,
      sharing a description of it is of potential value to medical educators.

PMID- 21961681
TI  - A mapping process for identifying and enhancing public health education in
      required medical student clerkships.
AB  - This is one of six short papers that describe additional innovations to help
      integrate public health into medical education; these were featured in the
      "Patients and Populations: Public Health in Medical Education" conference. They
      represent relatively new endeavors or curricular components that had not been
      explored in prior publications. Although evaluation data are lacking, it was felt
      that sharing a description of the mapping process for linking public health
      competencies to clinical clerkship activities at the University of Wisconsin
      School of Medicine and Public Health would be of value to medical educators.

PMID- 21961682
TI  - The integration of public health and prevention into all years of a medical
      school curriculum.
AB  - This is one of six short papers that describe additional innovations to help
      integrate public health into medical education; these were featured in the
      "Patients and Populations: Public Health in Medical Education" conference. They
      represent relatively new endeavors or curricular components that had not been
      explored in prior publications. Although evaluation data are lacking, it was felt
      that sharing a description of the public health, prevention, population health,
      and policy (P4) curriculum at the University of Arizona College of Medicine,
      Phoenix (UACOM-P), would be of value to medical educators.

PMID- 21961683
TI  - Innovative ways of integrating public health into the medical school curriculum.
AB  - This is one of six short papers that describe additional innovations to help
      integrate public health into medical education; these were featured in the
      "Patients and Populations: Public Health in Medical Education" conference. They
      represent relatively new endeavors or curricular components that had not been
      explored in prior publications. Although evaluation data are lacking, it was felt
      that sharing a description of the methods use by Morehouse School of Medicine to
      integrate public health in the curriculum would be of value to medical educators.

PMID- 21961684
TI  - Laying the foundation: a residency curriculum that supports informed advocacy by
      family physicians.
AB  - This is one of six short papers that describe additional innovations to help
      integrate public health into medical education; these were featured in the
      "Patients and Populations: Public Health in Medical Education" conference. They
      represent relatively new endeavors or curricular components that had not been
      explored in prior publications. Although evaluation data are lacking, it was felt
      that sharing a description of a longitudinal curriculum focused on the
      development of basic advocacy skills through practical activities in community
      assessment and engagement combined with legislative advocacy at the University of
      New Mexico would be of value to medical educators.

PMID- 21961685
TI  - The power of collaboration: integrating a preventive medicine-public health
      curriculum into a pediatric residency.
AB  - This is one of six short papers that describe additional innovations to help
      integrate public health into medical education; these were featured in the
      "Patients and Populations: Public Health in Medical Education" conference. They
      represent relatively new endeavors or curricular components that had not been
      explored in prior publications. Although evaluation data are lacking, it was
      considered to be of value to medical educators to share a brief description of
      the collaboration between the Division of Preventive, Occupational, and Aerospace
      Medicine and the Department of Pediatrics at Mayo Clinic to integrate a
      preventive medicine-public health curriculum into the pediatric residency.

PMID- 21961686
TI  - [Metformin in adolescents and adults with type 1 diabetes mellitus: not evidence
      based].
AB  - OBJECTIVE: Adolescents with type 1 diabetes mellitus (DM1) often have problems in
      achieving optimal glycaemic control. We investigated whether there is evidence of
      the beneficial effect of the addition of metformin to insulin therapy in
      adolescents with DM1. DESIGN: Systematic literature study. METHOD: Medline and
      Embase were searched for randomised double-blind trials in adolescents with DM1
      up to May 2011 inclusive. Two reviewers selected relevant articles based on
      title, summary and, if necessary, the full text. The quality of the methodology
      was also assessed. RESULTS: We found 2 studies in adolescents, of limited scope
      and duration. On this basis, it was decided that the search of the literature
      should be extended to adults with DM1, whereby 4 studies were found. All six
      trials were of good methodological quality, and included 196 patients in total.
      Clinical and statistical heterogeneity precluded pooling the results in a meta
      analysis. In one study in adolescents metformin treatment showed a reduction of
      HbA1c by 0.6% (95% CI: -1.16-0.04) and a slight decrease in daily total insulin
      dose. However, the treatment groups were not comparable at baseline. In the other
      studies, no significant changes in HbA1c were found. All studies showed decreased
      daily insulin dose; in four studies this was significant. Two studies showed a
      beneficial effect on weight or BMI. No serious side effects were recorded. One
      study showed an increase in hypoglycaemic episodes during metformin treatment.
      CONCLUSION: The possible benefit of adding metformin to insulin in adolescents
      and adults with type 1 diabetes remains unclear. A well-designed double-blind
      randomised trial carried out over a longer time period is required to assess
      whether metformin is of added value.

PMID- 21961687
TI  - [Premature sudden death--consider serious familial heart rhythm disturbances].
AB  - We describe 3 patients from a region in the centre of the Netherlands with
      several relatives who died prematurely from sudden cardiac arrest. These
      premature deaths appeared to be caused by a unique familial sudden death
      syndrome. These patients and their relatives did not present any distinguishable
      signs, symptoms or abnormalities on further examinations apart from premature
      cardiac arrest occurring in about 50% of the affected family members before the
      age of 60 years. Genetic analysis appeared to be the only means to identify
      family members at risk, carrying lethal changes in their DNA that presumably
      involve the DPP6-gene. Patients who survive a premature sudden cardiac arrest and
      relatives of patients who died prematurely from sudden cardiac arrest should be
      referred to a cardiogenetics outpatient clinic. Timely recognition of persons
      affected allows appropriate treatment and may implicate an implantable
      cardioverter defibrillator.

PMID- 21961688
TI  - [Switch of patients undergoing an endoscopic procedure].
AB  - Due to a switch in patients, the wrong patient, an 85-year-old man, underwent
      endoscopic retrograde cholangiopancreatography (ERCP) with papillotomy. The
      mistake was reported to the healthcare inspectorate. A systematic analysis of the
      incident using the "Prevention and recovery information system for monitoring and
      analysis" (PRISMA) method brought to light various shortcomings in the care
      process. Based on the PRISMA analysis various measures were taken, including the
      introduction of a time-out procedure with a checklist before carrying out an
      ERCP. These measures improved the quality of the care process.

PMID- 21961689
TI  - [Camphor poisoning following ingestion of mothballs 'for headache'].
AB  - BACKGROUND: Camphor is a toxic hydrocarbon, found in numerous over-the-counter
      medicinal products and chemist-shop items. The consequences of camphor poisoning
      depend on the dose, and severe poisoning can result in death. Ingestion of
      camphor can cause seizures, apnoea, renal insufficiency, raised hepatic enzyme
      levels, and vomiting resulting in chemical pneumonitis due to aspiration. CASE
      DESCRIPTION: We present the case of a 34-year-old female patient from the
      Dominican Republic who was brought into our accident and emergency department
      following the ingestion of camphor mothballs for persisting headaches. She was
      unconscious (Glasgow coma score: 3) and had severe acidosis (pH 6.59),
      respiratory insufficiency, electrolyte imbalance and raised hepatic enzyme and
      amylase levels. She was admitted to the intensive care unit and recovered
      quickly. Five days later, she was transferred to a general ward, where it became
      apparent that she was suffering from severe memory loss. After eight days she was
      discharged in good clinical condition, although she still suffered some memory
      loss. CONCLUSION: Many every-day products contain camphor. Poisoning can lead to
      an acute clinical picture, and immediate intensive care department treatment is
      obligatory. As there is no antidote available, supportive care is the only
      available option when poisoning occurs.

PMID- 21961690
TI  - [West Nile virus expanding in Europe].
AB  - The areas of Europe in which West Nile virus (WNV)-transmission to humans is
      observed have expanded over the last few years, with endemic circulation amongst
      animals of southern Europe. This situation calls for heightened vigilance to the
      clinical presentation of WNV infection in humans. The average incubation period
      lasts 2-6 days. Of those infected, 20% will experience a mild, non-specific
      disease presentation such as high fever, headache, myalgia, possibly with rash
      and lymphadenopathy; <1% will develop severe neurological symptoms. Rare
      complications include: myelitis, optic neuritis, rhombencephalitis,
      polyradiculitis, myocarditis, pancreatitis and fulminant hepatitis. Clinicians
      should take WNV infection into consideration when making a differential diagnosis
      for such symptoms in patients who have returned from areas with potential virus
      circulation. Given the increase in the spread of WNV within Europe, this now
      holds true for continental travellers as well as those destined for the Americas,
      Africa and Asia. It is important to include the patient's travel history,
      clinical symptoms and any occurrences of vaccination against viruses causing
      Japanese encephalitis, tick-borne encephalitis and yellow fever into the
      diagnostic workup, as the antibodies against these diseases show cross
      reactivity.

PMID- 21961691
TI  - Determination of anisotropic surface characteristics of different phyllosilicates
      by direct force measurements.
AB  - To fundamentally understand the electrokinetic behavior of clay minerals, it is
      necessary to study the anisotropic surface charge properties of clay surfaces. In
      this study, two 2:1 layer natural minerals, talc and muscovite, were chosen as
      representatives of magnesium and aluminum phyllosilicate minerals, respectively.
      The molecularly smooth basal planes of both platy minerals were obtained by
      cleavage along the basal planes, while suitable edge surfaces were prepared by an
      ultramicrotome cutting technique. Silicon nitride atomic force microscopy tip was
      used as a probe to study the interaction forces between the tip and clay
      basal/edge surfaces in aqueous solutions of various pH values. The measured
      interaction force profiles between the tip and clay basal/edge surfaces were
      fitted with the classical DLVO (Derjaguin-Landau-Verwey-Overbeek) theory, which
      allows direct determination of electrical surface potential of talc and muscovite
      surfaces. The surface potential of muscovite basal planes was found to be
      significantly more negative than the basal plane of talc, both being pH
      insensitive. In contrast, the surface potential of edge surfaces was highly pH
      dependent, exhibiting a point of zero charge (PZC) at pH 7.5 and 8.1 for edges of
      muscovite and talc, respectively. The observed differences in surface potential
      of basal planes and edge surfaces for both talc and muscovite are closely related
      to their crystal structure and ionization characteristics. The protonation
      reactivity and the contribution of each surface group to the surface charging
      behavior are modeled using their protonation constants.

PMID- 21961692
TI  - Matrix Gla protein inhibits ectopic calcification by a direct interaction with
      hydroxyapatite crystals.
AB  - Mice lacking the gene encoding matrix gla protein (MGP) exhibit massive mineral
      deposition in blood vessels and die soon after birth. We hypothesize that MGP
      prevents arterial calcification by adsorbing to growing hydroxyapatite (HA)
      crystals. To test this, we have used a combined experimental-computational
      approach. We synthesized peptides covering the entire sequence of human MGP,
      which contains three sites of serine phosphorylation and five sites of gamma
      carboxylation, and studied their effects on HA crystal growth using a constant
      composition autotitration assay. In parallel studies, the interactions of these
      sequences with the {100} and {001} faces of HA were analyzed using atomistic
      molecular dynamics (MD) simulations. YGlapS (amino acids 1-14 of human MGP) and
      SK-Gla (MGP43-56) adsorbed rapidly to the {100} and {001} faces and strongly
      inhibited HA growth (IC(50) = 2.96 MUg/mL and 4.96 MUg/mL, respectively). QR-Gla
      (MGP29-42) adsorbed more slowly and was a moderate growth inhibitor, while the
      remaining three (nonpost-translationally modified) peptides had little or no
      effect in either analysis. Substitution of gla with glutamic acid reduced the
      adsorption and inhibition activities of SK-Gla and (to a lesser extent) QR-Gla
      but not YGlapS; substitution of phosphoserine with serine reduced the inhibitory
      potency of YGlapS. These studies suggest that MGP prevents arterial calcification
      by a direct interaction with HA crystals that involves both phosphate groups and
      gla residues of the protein. The strong correlation between simulated adsorption
      and measured growth inhibition indicates that MD provides a powerful tool to
      predict the effects of proteins and peptides on crystal formation.

PMID- 21961693
TI  - A Poisson regression approach for modelling spatial autocorrelation between
      geographically referenced observations.
AB  - BACKGROUND: Analytic methods commonly used in epidemiology do not account for
      spatial correlation between observations. In regression analyses, omission of
      that autocorrelation can bias parameter estimates and yield incorrect standard
      error estimates. METHODS: We used age standardised incidence ratios (SIRs) of
      esophageal cancer (EC) from the Babol cancer registry from 2001 to 2005, and
      extracted socioeconomic indices from the Statistical Centre of Iran. The
      following models for SIR were used: (1) Poisson regression with agglomeration
      specific nonspatial random effects; (2) Poisson regression with agglomeration
      specific spatial random effects. Distance-based and neighbourhood-based
      autocorrelation structures were used for defining the spatial random effects and
      a pseudolikelihood approach was applied to estimate model parameters. The
      Bayesian information criterion (BIC), Akaike's information criterion (AIC) and
      adjusted pseudo R2, were used for model comparison. RESULTS: A Gaussian
      semivariogram with an effective range of 225 km best fit spatial autocorrelation
      in agglomeration-level EC incidence. The Moran's I index was greater than its
      expected value indicating systematic geographical clustering of EC. The distance
      based and neighbourhood-based Poisson regression estimates were generally
      similar. When residual spatial dependence was modelled, point and interval
      estimates of covariate effects were different to those obtained from the
      nonspatial Poisson model. CONCLUSIONS: The spatial pattern evident in the EC SIR
      and the observation that point estimates and standard errors differed depending
      on the modelling approach indicate the importance of accounting for residual
      spatial correlation in analyses of EC incidence in the Caspian region of Iran.
      Our results also illustrate that spatial smoothing must be applied with care.

PMID- 21961694
TI  - A highly efficient rice green tissue protoplast system for transient gene
      expression and studying light/chloroplast-related processes.
AB  - BACKGROUND: Plant protoplasts, a proven physiological and versatile cell system,
      are widely used in high-throughput analysis and functional characterization of
      genes. Green protoplasts have been successfully used in investigations of plant
      signal transduction pathways related to hormones, metabolites and environmental
      challenges. In rice, protoplasts are commonly prepared from suspension cultured
      cells or etiolated seedlings, but only a few studies have explored the use of
      protoplasts from rice green tissue. RESULTS: Here, we report a simplified method
      for isolating protoplasts from normally cultivated young rice green tissue
      without the need for unnecessary chemicals and a vacuum device. Transfections of
      the generated protoplasts with plasmids of a wide range of sizes (4.5-13 kb) and
      co-transfections with multiple plasmids achieved impressively high efficiencies
      and allowed evaluations by 1) protein immunoblotting analysis, 2) subcellular
      localization assays, and 3) protein-protein interaction analysis by bimolecular
      fluorescence complementation (BiFC) and firefly luciferase complementation (FLC).
      Importantly, the rice green tissue protoplasts were photosynthetically active and
      sensitive to the retrograde plastid signaling inducer norflurazon (NF). Transient
      expression of the GFP-tagged light-related transcription factor OsGLK1 markedly
      upregulated transcript levels of the endogeneous photosynthetic genes OsLhcb1,
      OsLhcp, GADPH and RbcS, which were reduced to some extent by NF treatment in the
      rice green tissue protoplasts. CONCLUSIONS: We show here a simplified and highly
      efficient transient gene expression system using photosynthetically active rice
      green tissue protoplasts and its broad applications in protein immunoblot,
      localization and protein-protein interaction assays. These rice green tissue
      protoplasts will be particularly useful in studies of light/chloroplast-related
      processes.

PMID- 21961695
TI  - Conformational analysis of 18-azacrown-6 and its bonding with late first
      transition series divalent metals: insight from DFT combined with NPA and QTAIM
      analyses.
AB  - Density functional theory calculations, together with quantum theory of atoms in
      molecules (QTAIM) analyses, have been performed to investigate 18-azacrown-6
      complexes of the high-spin late first transition series divalent metal ions in
      the gas phase and, in some cases, in aqueous solution simulated by a polarizable
      continuum model. Six intramolecular H-H bonding interactions in the meso
      complexes are found to arise from folding of the ligand upon its electrostatic
      interaction with the metal ions, which are largely absent in the lowest-energy
      C(2h) conformer of the free ligand. The ligand-to-metal charge transfer obtained
      from QTAIM analysis, among other things, is found to be an important factor that
      controls the stability of these complexes. The inter-relationship between the
      ligand preorganization energy, the zero-point corrected formation energy of the
      metal complexes, and the H-H bonding pair distances, as well as the dependence of
      the electron density and the total energy density at the H-H bond critical points
      on the H-H bonding pair distances, provides a physical basis for understanding
      and explaining the stabilizing nature of these closed-shell interactions, which
      are often viewed as steric clashes that lead to complex destabilization.

PMID- 21961696
TI  - Facile preparation of magnetic separable powdered-activated-carbon/Ni adsorbent
      and its application in removal of perfluorooctane sulfonate (PFOS) from aqueous
      solution.
AB  - The main aim of this study was to synthesize magnetic separable Nickel/powdered
      activated carbon (Ni/PAC) and its application as an adsorbent for removal of PFOS
      from aqueous solution. In this work, the synthesized adsorbent using simple
      method was characterized by using X-ray diffractionometer (XRD), surface area and
      pore size analyzer, vibrating sample magnetometer (VSM), and high resolution
      transmission electron microscope (HRTEM). The surface area, pore volume and pore
      size of synthesized PAC was 1521.8 m(2)g(-1), 0.96 cm(3)g(-1), 2.54 nm,
      respectively. Different kinetic models: the pseudo-first-order model, the pseudo
      second-order model, and three adsorption isotherms--Langmuir, Freundlich and
      Temkin--were applied to study the sorption kinetics and isothermal behavior of
      PFOS onto the surface of an as-prepared adsorbent. The rate constant using the
      pseudo-second-order model for removal of 150 ppm PFOS was estimated as 8.82*10(
      5) and 1.64*10(-4) for PAC and 40% Ni/PAC, respectively. Our results demonstrated
      that the composite adsorbents exhibited a clear magnetic hysteretic behavior,
      indicating the potential practical application in magnetic separation of
      adsorbents from aqueous solution phase as well.

PMID- 21961697
TI  - Age at diagnosis of diabetes in Appalachia.
AB  - BACKGROUND: Appalachia is a region of the United States noted for the poverty and
      poor health outcomes of its residents. Residents of the poorest Appalachian
      counties have a high prevalence of diabetes and risk factors (obesity, low
      income, low education, etc.) for type 2 diabetes. However, diabetes prevalence
      exceeds what these risk factors alone explain. Based on this, the history of poor
      health outcomes in Appalachia, and personally observed high rates of childhood
      obesity and lack of concern about prediabetes, we speculated that people in
      Appalachia with diagnosed diabetes might tend to be diagnosed younger than their
      non-Appalachian counterparts. METHODS: We used data from the Behavioral Risk
      Factor Surveillance System (2006-2008). We compared age at diagnosis among
      counties by Appalachian Regional Commission-defined level of economic
      development. To account for risk differences, we constructed a model for average
      age at diagnosis of diabetes, adjusting for county economic development, obesity,
      income, sedentary lifestyle, and other covariates. FINDINGS: After adjustment for
      risk factors for diabetes, people in distressed or at-risk counties (the least
      economically developed) had their diabetes diagnosed two to three years younger
      than comparable people in non-Appalachian counties. No significant differences
      between non-Appalachian counties and Appalachian counties at higher levels of
      economic development remained after adjusting. CONCLUSIONS: People in distressed
      and at-risk counties have poor access to care, and are unlikely to develop
      diabetes at the same age as their non-Appalachian counterparts but be diagnosed
      sooner. Therefore, people in distressed and at-risk counties are likely
      developing diabetes at younger ages. We recommend that steps to reduce health
      disparities between the poorest Appalachian counties and non-Appalachian counties
      be considered.

PMID- 21961698
TI  - Enhanced luminescent iridium(III) complexes bearing aryltriazole cyclometallated
      ligands.
AB  - Herein we report the synthesis of 4-aryl-1-benzyl-1H-1,2,3-triazoles (atl), made
      via "Click chemistry" and their incorporation as cyclometallating ligands into
      new heteroleptic iridium(III) complexes containing diimine (N(^)N) ancillary
      ligands 2,2'-bipyridine (bpy) and 4,4'-di-tert-butyl-2,2'-bipyridine (dtBubpy).
      Depending on decoration, these complexes emit from the yellow to sky blue in
      acetonitrile (ACN) solution at room temperature (RT). Their emission energies are
      slightly blue-shifted and their photoluminescent quantum efficiencies are
      markedly higher (between 25 and 80%) than analogous (C(^)N)(2)Ir(N(^)N)(+) type
      complexes, where C(^)N is a decorated 2-phenylpyridinato ligand. This increased
      brilliance is in part due to the presence of the benzyl groups, which act to
      sterically shield the iridium metal center. X-ray crystallographic analyses of
      two of the atl complexes corroborate this assertion. Their electrochemistry is
      reversible, thus making these complexes amenable for inclusion in light-emitting
      electrochemical cells (LEECs). A parallel computational investigation supports
      the experimental findings and demonstrates that for all complexes included in
      this study, the highest occupied molecular orbital (HOMO) is located on both the
      aryl fragment of the atl ligands and the iridium metal while the lowest
      unoccupied molecular orbital (LUMO) is located essentially exclusively on the
      ancillary ligand.

PMID- 21961704
TI  - Interstitial lung disease in rheumatoid arthritis: response to IL-6R blockade.

PMID- 21961699
TI  - Two new "protected" oxyphors for biological oximetry: properties and application
      in tumor imaging.
AB  - We report the synthesis, calibration, and examples of application of two new
      phosphorescent probes, Oxyphor R4 and Oxyphor G4, optimized specifically for in
      vivo oxygen imaging by phosphorescence quenching. These "protected" dendritic
      probes can operate in either albumin-rich (blood plasma) or albumin-free
      (interstitial space) environments at all physiological oxygen concentrations,
      from normoxic to deep hypoxic conditions. Oxyphors R4 and G4 are derived from
      phosphorescent Pd-meso-tetra-(3,5-dicarboxyphenyl)-porphyrin (PdP) or Pd-meso
      tetra-(3,5-dicarboxyphenyl)-tetrabenzoporphyrin (PdTBP), respectively, and
      possess features common for protected dendritic probes, i.e., hydrophobic
      dendritic encapsulation of phosphorescent metalloporphyrins and hydrophilic
      PEGylated periphery. The new Oxyphors are highly soluble in aqueous environments
      and do not permeate biological membranes. The probes were calibrated under
      physiological conditions (pH 6.4-7.8) and temperatures (22-38  degrees C),
      showing high stability, reproducibility of signals, and lack of interactions with
      biological solutes. Oxyphor G4 was used to dynamically image intravascular and
      interstitial oxygenation in murine tumors in vivo. The physiological relevance of
      the measurements was demonstrated by dynamically recording changes in tissue
      oxygenation during application of anesthesia (isofluorane). These experiments
      revealed that changes in isofluorane concentration significantly affect tissue
      oxygenation.

PMID- 21961705
TI  - Three-dimensional structure of mannosyl-3-phosphoglycerate phosphatase from
      Thermus thermophilus HB27: a new member of the haloalcanoic acid dehalogenase
      superfamily.
AB  - Mannosyl-3-phosphoglycerate phosphatase (MpgP) is a key mediator in the
      physiological response to thermal and osmotic stresses, catalyzing the hydrolysis
      of mannosyl-3-phosphoglycerate (MPG) to the final product, alpha
      mannosylglycerate. MpgP is a metal-dependent haloalcanoic acid dehalogenase-like
      (HAD-like) phosphatase, preserving the catalytic motifs I-IV of the HAD core
      domain, and classified as a Cof-type MPGP (HAD-IIB-MPGP family; SCOP [117505]) on
      the basis of its C2B cap insertion module. Herein, the crystallographic
      structures of Thermus thermophilus HB27 MpgP in its apo form and in complex with
      substrates, substrate analogues, and inhibitors are reported. Two distinct enzyme
      conformations, open and closed, are catalytically relevant. Apo-MpgP is primarily
      found in the open state, while holo-MpgP, in complex with the reaction products,
      is found in the closed state. Enzyme activation entails a structural
      rearrangement of motifs I and IV with concomitant binding of the cocatalytic
      Mg(2+) ion. The closure motion of the C2B domain is subsequently triggered by the
      anchoring of the phosphoryl group to the cocatalytic metal center, and by Arg167
      fixing the mannosyl moiety inside the catalytic pocket. The results led to the
      proposal that in T. thermophilus HB27 MpgP the phosphoryl transfer employs a
      concerted D(N)S(N) mechanism with assistance of proton transfer from the general
      acid Asp8, forming a short-lived PO(3)(-) intermediate that is attacked by a
      nucleophilic water molecule. These results provide new insights into a possible
      continuum of phosphoryl transfer mechanisms, ranging between those purely
      associative and dissociative, as well as a picture of the main mechanistic
      aspects of phosphoryl monoester transfer catalysis, common to other members of
      the HAD superfamily.

PMID- 21961706
TI  - Monitoring of artemisinin, dihydroartemisinin, and artemether in environmental
      matrices using high-performance liquid chromatography-tandem mass spectrometry
      (LC-MS/MS).
AB  - The area cultivated with Artemisia annua for the extraction of the antimalarial
      compound artemisinin is increasing, but the environmental impact of this
      cultivation has not yet been studied. A sensitive and robust method using liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) was developed for the
      determination of artemisinin in soil. Dihydroartemisinin and artemether were
      included in the method, and performance on analytical columns of both traditional
      C(18) phenyl-hexyl and porous shell particles-based Kinetex types was
      characterized. The versatility of the method was demonstrated on surface water
      and groundwater samples and plant extracts. The limit of detection was 55, 30 (25
      ng/g soil), and 4 ng/mL for dihydroartemisinin, artemisinin, and artemether,
      respectively. Method performance was demonstrated using naturally contaminated
      soil samples from A. annua fields in Kenya. The highest observed concentrations
      were above EC(10) for lettuce growth. Monitoring of artemisinin in soil with A.
      annua crop production seems necessary to further understand the impact in the
      environment.

PMID- 21961707
TI  - Addiction circuitry in the human brain.
AB  - A major challenge in understanding substance-use disorders lies in uncovering why
      some individuals become addicted when exposed to drugs, whereas others do not.
      Although genetic, developmental, and environmental factors are recognized as
      major contributors to a person's risk of becoming addicted, the neurobiological
      processes that underlie this vulnerability are still poorly understood. Imaging
      studies suggest that individual variations in key dopamine-modulated brain
      circuits, including circuits involved in reward, memory, executive function, and
      motivation, contribute to some of the differences in addiction vulnerability. A
      better understanding of the main circuits affected by chronic drug use and the
      influence of social stressors, developmental trajectories, and genetic background
      on these circuits is bound to lead to a better understanding of addiction and to
      more effective strategies for the prevention and treatment of substance-use
      disorders.

PMID- 21961708
TI  - Molecular subtype analysis determines the association of advanced breast cancer
      in Egypt with favorable biology.
AB  - BACKGROUND: Prognostic markers and molecular breast cancer subtypes reflect
      underlying biological tumor behavior and are important for patient management.
      Compared to Western countries, women in North Africa are less likely to be
      prognosticated and treated based on well-characterized markers such as the
      estrogen receptor (ER), progesterone receptor (PR) and Her2. We conducted this
      study to determine the prevalence of breast cancer molecular subtypes in the
      North African country of Egypt as a measure of underlying biological
      characteristics driving tumor manifestations. METHODS: To determine molecular
      subtypes we characterized over 200 tumor specimens obtained from Egypt by
      performing ER, PR, Her2, CK5/6, EGFR and Ki67 immunohistochemistry. RESULTS: Our
      study demonstrated that the Luminal A subtype, associated with favorable
      prognosis, was found in nearly 45% of cases examined. However, the basal-like
      subtype, associated with poor prognosis, was found in 11% of cases. These
      findings are in sharp contrast to other parts of Africa in which the basal-like
      subtype is over-represented. CONCLUSIONS: Egyptians appear to have favorable
      underlying biology, albeit having advanced disease at diagnosis. These data
      suggest that Egyptians would largely profit from early detection of their
      disease. Intervention at the public health level, including education on the
      benefits of early detection is necessary and would likely have tremendous impact
      on breast cancer outcome in Egypt.

PMID- 21961709
TI  - Designing hypothesis of substituted benzoxazinones as HIV-1 reverse transcriptase
      inhibitors: QSAR approach.
AB  - A linear quantitative structure activity relationship (QSAR) model is presented
      for predicting human immunodeficiency virus-1 (HIV-1) reverse transcriptase
      enzyme inhibition. The 2D QSAR and 3D-QSAR models were developed by stepwise
      multiple linear regression, partial least square (PLS) regression and k-nearest
      neighbor-molecular field analysis, PLS regression, respectively using a database
      consisting of 33 recently discovered benzoxazinones. The primary findings of this
      study is that the number of hydrogen atoms, number of (-NH2) group connected with
      solitary single bond alters the inhibition of HIV-1 reverse transcriptase.
      Further, presence of electrostatic, hydrophobic and steric field descriptors
      significantly affects the ability of benzoxazinone derivatives to inhibit HIV-1
      reverse transcriptase. The selected descriptors could serve as a primer for the
      design of novel and potent antagonists of HIV-1 reverse transcriptase.

PMID- 21961710
TI  - The SWAN song: Study of Women's Health Across the Nation's recurring themes.
AB  - Reproductive health can be a reflection of overall health. It follows that
      abnormalities of reproductive milestones may be a manifestation of unhealthy
      aging. Since 1994, the Study of Women's Health Across the Nation (SWAN) has
      assessed how menopause and the process of that transition may affect future
      health. Themes have emerged from SWAN associating patterns of hormones and
      symptoms with metabolic status.The nature of these relationships vary as women
      traverse the menopause and ovarian hormone production ceases. This review
      describes these cross-cutting themes and their possible meaning for the health of
      the mid-life woman.

PMID- 21961712
TI  - Adiposity and the menopausal transition.
AB  - This review summarizes the published literature on the potentially circular
      relationship between adiposity and the menopause. Although data are limited,
      current information suggests there are substantial effects of obesity and
      adiposity on the magnitude of hormone changes experienced during the transition,
      as well as on the risks of chronic disease resulting from the menopause
      transition. However, evidence regarding the reverse, namely, effects of the
      menopause transition and its associated hormone changes on weight gain and
      redistribution of body fat, are inconclusive.

PMID- 21961711
TI  - The timing of the age at which natural menopause occurs.
AB  - The timing of natural menopause is a clinically important indicator of longevity
      and risk of morbidity and mortality. Demographic, menstrual, reproductive,
      familial, genetic, and lifestyle factors seem to be important in this timing.
      Smoking, lower parity and poor socioeconomic status are associated with earlier
      menopause. However, a number of relationships have been inconsistent; others
      remain largely unexplored. Much remains to be learned about factors that affect
      follicular atresia and the onset and duration of perimenopause and the timing of
      the natural menopause. Knowledge about these relationships offers women and their
      health care providers enhanced understanding and choices to deal with menopause.

PMID- 21961713
TI  - Reproductive hormones and the menopause transition.
AB  - The hormonal correlates of reproductive aging and the menopause transition
      reflect an initial loss of the follicle cohort, while a responsive ovary remains,
      and an eventual complete loss of follicle response, with persistent
      hypergonadotropic amenorrhea. The physiology of the process is described, along
      with key findings of relevant studies, with an emphasis on the Study of Women's
      Health Across the Nation. A clinical framework is provided to help clinicians to
      forecast the major milestones of the menopausal transition and to predict
      potential symptoms or disease.

PMID- 21961714
TI  - Adrenal androgens and the menopausal transition.
AB  - The concept that adrenal androgen production gradually declines with age has
      changed after analysis of longitudinal data from the Study of Women's Health
      Across the Nation (SWAN). It is now recognized that 4 adrenal androgens rise
      during the menopausal transition in most women. Ethnic and individual differences
      in sex steroids are more apparent in circulating adrenal steroids than in either
      estradiol or cyclic ovarian steroid hormone profiles, particularly during the
      early and late perimenopause. Thus, adrenal steroid production may play a larger
      role in the occurrence of symptoms and the potential for healthier aging than
      previously recognized.

PMID- 21961715
TI  - The menopausal transition and cardiovascular risk.
AB  - The incidence of cardiovascular disease, which is the leading single cause of
      death among women, increases substantially after menopause. This may be related
      to adverse changes in cardiovascular risk factors that occur during the
      menopausal transition. Proatherogenic changes in lipid and apolipoprotein
      profiles seem to be specifically related to ovarian aging; unfavorable changes in
      other cardiovascular risk factors may be influenced more by chronologic aging.
      Whether these changes are due to aging or to menopause itself, increased
      attention to risk factor modification in the pre- and perimenopausal years will
      help reduce future cardiovascular disease risk among women.

PMID- 21961716
TI  - Vasomotor symptoms and menopause: findings from the Study of Women's Health
      across the Nation.
AB  - Vasomotor symptoms (VMS), or hot flashes and night sweats, are often considered
      the cardinal symptoms of menopause. SWAN, one of the largest and most ethnically
      diverse longitudinal studies of the menopausal transition, has allowed unique
      insights into VMS. Specifically, SWAN has helped yield important information
      about the prevalence of, racial/ethnic differences in, risk factors for, and
      implications of VMS for midlife women's mental and physical health. We have
      reviewed the literature on VMS, emphasizing findings that have emerged from SWAN
      and new areas of inquiry in the area of VMS.

PMID- 21961717
TI  - Bone and the perimenopause.
AB  - Loss of ovarian function has a profound impact on female skeletal health. Bone
      mineral density findings from the Study of Women's Health Across the Nation
      demonstrate an accelerated rate of bone loss during the menopausal transition.
      The greatest reduction occurs in the year before the final menstrual period and
      the first 2 years thereafter. Clinical management includes maintenance of
      adequate dietary calcium and vitamin D intake, attention to modifiable risk
      factors, and osteoporosis screening. Indications, benefits, and risks of
      pharmacologic osteoporosis therapy should be assessed individually; there are
      currently no established guidelines addressing the treatment and prevention of
      osteoporosis in perimenopausal women.

PMID- 21961718
TI  - Perimenopause and cognition.
AB  - The impact of perimenopause on cognition seems to be characterized by an absence
      of improved scores rather than a decline. In the SWAN, the perimenopausal
      decrement in cognitive performance was not accounted for; however, increases in
      anxiety and depressive symptoms had independent, unfavorable effects on
      performance. Estradiol has been found to protect against changes resulting from
      serotonin withdrawal and defend against changes from cholinergic depletion. There
      is support for the critical timing hypothesis--that estrogen benefits cognitive
      function when instituted early, but not later. The menopausal transition may
      affect cognitive function in older age owing to worsened cardiovascular risk
      factors.

PMID- 21961720
TI  - Sleep during the perimenopause: a SWAN story.
AB  - Is there evidence for a perimenopausal sleep disorder? We address this question
      in our presentation of the Study of Women's Health Across the Nation (SWAN)
      "sleep story," in which we summarize and discuss data addressing sleep quality,
      objective measures of sleep patterns, and sleep disorders that have been
      published to date by the SWAN and the ancillary SWAN Sleep Study. We describe
      what has been learned about sleep during the perimenopause. Analyses exploring
      racial/ethnic diversity and the role of hot flashes and mood disturbance in sleep
      perimenopause associations are described. Implications for clinical practice are
      considered.

PMID- 21961719
TI  - Physical activity and health during the menopausal transition.
AB  - The benefits of regular physical activity are well established, but evidence for
      a protective effect against the adverse health consequences accompanying the
      menopausal transition is limited. This article reviews that evidence, concluding
      that more physical activity is generally associated with fewer somatic and mood
      symptoms. Physical activity seems to minimize weight gain and changes in body
      composition and fat distribution experienced at midlife and might attenuate the
      rapid bone density loss that occurs. Given these benefits, clinicians treating
      perimenopausal women should encourage their patients to follow guidelines for
      physical activity (>=150 minutes a week of moderate-intensity activity).

PMID- 21961721
TI  - The perimenopause and sexual functioning.
AB  - Sexual functioning is an important component of women's lives. Sexual
      functioning, however, declines with age, and there is much debate about the
      contribution of menopause to sexual activity and functioning...The present
      article covers cross-sectional and longitudinal community-based research on
      sexual functioning during the perimenopause. .The.article addresses the relative
      contributions of perimenopause and other.factors (e.g., relationship with
      partner, previous sexual enjoyment, psychosocial.factors and health) to sexual
      functioning.

PMID- 21961724
TI  - Foreword: perimenopause.

PMID- 21961722
TI  - Menstruation and the menopausal transition.
AB  - This paper characterizes changes in menstrual bleeding during
      perimenopause,including bleeding changes that represent markers of the menopausal
      transition. Recent results from the Study of Women's Health Across the Nation and
      other cohort studies are reviewed. Emerging data describing subpopulation
      differences in the transition experience are highlighted. When treating women in
      the midlife, clinicians should pay careful attention to medical factors,
      including both conditions and treatments, that may increase menstrual blood loss
      or alter menstrual cycle characteristics sufficiently to obscure the onset of the
      menopausal transition or the final menstrual period.

PMID- 21961723
TI  - Mood and menopause: findings from the Study of Women's Health Across the Nation
      (SWAN) over 10 years.
AB  - Women are twice as likely as men to suffer from depressive symptoms/disorder.
      Research has focused on physiologic and psychosocial differences between men and
      women; an important target of study has been periods of reproductive changes.
      Controversy has existed regarding the extent to which the menopausal transition
      or postmenopause increases the risk for depressive symptoms/disorders. This paper
      presents findings from analyses of data from the SWAN study and an ancillary
      study on mental health. We found that risk for high depressive symptoms and
      disorder is greater during and possibly after the menopausal transition. Other
      factors contribute to risk for depression.

PMID- 21961725
TI  - The Study of Women's Health Across the Nation (SWAN) .

PMID- 21961726
TI  - Role of protein kinase C and epidermal growth factor receptor signalling in
      growth stimulation by neurotensin in colon carcinoma cells.
AB  - BACKGROUND: Neurotensin has been found to promote colon carcinogenesis in rats
      and mice, and proliferation of human colon carcinoma cell lines, but the
      mechanisms involved are not clear. We have examined signalling pathways activated
      by neurotensin in colorectal and pancreatic carcinoma cells. METHODS: Colon
      carcinoma cell lines HCT116 and HT29 and pancreatic adenocarcinoma cell line Panc
      1 were cultured and stimulated with neurotensin or epidermal growth factor (EGF).
      DNA synthesis was determined by incorporation of radiolabelled thymidine into
      DNA. Levels and phosphorylation of proteins in signalling pathways were assessed
      by Western blotting. RESULTS: Neurotensin stimulated the phosphorylation of both
      extracellular signal-regulated kinase (ERK) and Akt in all three cell lines, but
      apparently did so through different pathways. In Panc-1 cells, neurotensin
      induced phosphorylation of ERK, but not Akt, was dependent on protein kinase C
      (PKC), whereas an inhibitor of the beta-isoform of phosphoinositide 3-kinase
      (PI3K), TGX221, abolished neurotensin-induced Akt phosphorylation in these cells,
      and there was no evidence of EGF receptor (EGFR) transactivation. In HT29 cells,
      in contrast, the EGFR tyrosine kinase inhibitor gefitinib blocked neurotensin
      stimulated phosphorylation of both ERK and Akt, indicating transactivation of
      EGFR, independently of PKC. In HCT116 cells, neurotensin induced both a PKC
      dependent phosphorylation of ERK and a metalloproteinase-mediated transactivation
      of EGFR that was associated with a gefitinib-sensitive phosphorylation of the
      downstream adaptor protein Shc. The activation of Akt was also inhibited by
      gefitinib, but only partly, suggesting a mechanism in addition to EGFR
      transactivation. Inhibition of PKC blocked neurotensin-induced DNA synthesis in
      HCT116 cells. CONCLUSIONS: While acting predominantly through PKC in Panc-1 cells
      and via EGFR transactivation in HT29 cells, neurotensin used both these pathways
      in HCT116 cells. In these cells, neurotensin-induced activation of ERK and
      stimulation of DNA synthesis was PKC-dependent, whereas activation of the
      PI3K/Akt pathway was mediated by stimulation of metalloproteinases and subsequent
      transactivation of the EGFR. Thus, the data show that the signalling mechanisms
      mediating the effects of neurotensin involve multiple pathways and are cell
      dependent.

PMID- 21961727
TI  - Simultaneous activity assay of two transglutaminase isozymes, blood coagulation
      factor XIII and transglutaminase 2, by use of fibrinogen arrays.
AB  - We developed an on-chip activity assay system to simultaneously determine the
      transamidating activities of blood coagulation factor XIII (FXIII) and
      transglutaminase 2 (TG2) by use of fibrinogen arrays. FXIII and TG2 are
      transglutaminase family members that are involved in various physiological
      functions, including vascular pathophysiology, bone development, and cancer
      progression. However, investigation of their differential functions is limited by
      the lack of high-throughput and isozyme-specific activity assays. For the on-chip
      activity assay, we fabricated protein arrays by immobilizing fibrinogen onto the
      3-aminopropyltrimethoxysilane surface of well-type arrays, and we determined
      transamidating activity by probing biotinylated fibrinogen with Cy3-conjugated
      streptavidin on arrays. We optimized assay conditions, such as buffer pH,
      concentrations of dithiothreitol and 5-(biotinamido)pentylamine, and incubation
      time, and we created equations to determine specific FXIII and TG2 activities in
      samples. We successfully applied this assay system to monitor changes in FXIII
      and TG2 activities in THP-1 monocytic cells differentiated with phorbol 12
      myristate13-acetate and interleukin-4. This activity assay is sensitive and
      suitable for high-throughput determination of FXIII and TG2 activities and thus
      has a strong potential for investigating the differential functions of these
      isozymes in cell signaling and cardiovascular pathophysiology research.

PMID- 21961728
TI  - Inequality in provider continuity for children by Australian general
      practitioners.
AB  - BACKGROUND: There is little published on provider continuity in Australian
      general practice and none on its effect on inequality of care for children.
      METHOD: Questionnaire administered to parents of the ACT Kindergarten Health
      Screen asking the name of their child's usual GP and practice address between
      2001 and 2008. RESULTS: Parents of 30,789 children named 433 GPs and 141
      practices. In each year, an average of 77% of parents could name both the GP and
      the practice, an average of 11% of parents could name only the practice, and an
      average of 12% of parents could name neither. In each year, 25% of parents could
      not name a usual GP for children of Aboriginal or Torres Straight Islander
      descent, or children born outside of Australia, compared to 10% of all other
      children (p = < 0.0001). The frequency of GPs displaying continuity of care
      varied over time with 19% of GPs being present in the ACT in only one year and
      39% of GPs being present in every year over the eight years of study. GPs
      displayed two different forms of transience either by working in more than one
      practice in each year (5% of GPs), or by not being present in the ACT region from
      one year to the next (15% of GPs). Fewer parents nominated transient GPs as their
      child's GP compared to choosing GPs who displayed continuity (p < 0.001).
      CONCLUSIONS: Many GPs (39%) were reported to provide continuity of care for in
      the ACT region and some GPs (20%) displayed transient care. Indigenous children
      or children born outside of Australia had less equity of access to a nominated GP
      than all other children. Such inequity might disappear if voluntary registration
      of children was adopted in Australian general practice.

PMID- 21961729
TI  - Adult norms and test-retest reliability for the Months Backward test: durational
      and response accuracy measures.
AB  - The aim of this study was to present adult norms and to estimate the test-retest
      reliability for durational and response accuracy measures on the word sequence
      production test, Months Backward. A total of 216 neurologically intact adults
      (aged 18-88) stratified by sex, age, and education took the test at maximum
      speed. Errors and speech duration were recorded. A retest was conducted with 40
      participants after 3 weeks. Altogether 94% of the participants completed the test
      without error. Errors were associated with slow performance. Duration was
      predicted by years of education (beta = -0.39) and self-reported dyslexia (beta =
      0.19). The test-retest reliability was 0.82 for duration and 0.97 for errors. A
      regression formula for adjustment of logarithmically transformed duration scores
      is provided.

PMID- 21961732
TI  - A bronze matryoshka: the discrete intermetalloid cluster [Sn@Cu12@Sn20](12-) in
      the ternary phases A12Cu12Sn21 (A = Na, K).
AB  - The synthesis and crystal structure of the first ternary A-Cu-Sn intermetallic
      phases for the heavier alkali metals A = Na to Cs is reported. The title
      compounds A(12)Cu(12)Sn(21) show discrete 33-atom intermetalloid Cu-Sn clusters
      {Sn@Cu(12)@Sn(20)}, which are composed of {Sn(20)} pentagonal dodecahedra
      surrounding {Cu(12)} icosahedra with single Sn atoms at the center.
      Na(12)Cu(12)Sn(21) and K(12)Cu(12)Sn(21) were characterized by single-crystal XRD
      studies, and the successful synthesis of analogous A-Cu-Sn compounds with A = Rb
      and Cs is deduced from powder XRD data. The isotypic A(12)Cu(12)Sn(21) phases
      crystallize in the cubic space group Pn 3m (No. 224), with the Cu-Sn clusters
      adopting a face centered cubic arrangement. A formal charge of 12- can be
      assigned to the {Sn@Cu(12)@Sn(20)} cluster unit, and the interpretation of the
      title compounds as salt-like intermetallic phases featuring discrete anionic
      intermetalloid [Sn@Cu(12)@Sn(20)](12-) clusters separated by alkali metal cations
      is supported by electronic structure calculations. For both Na(12)Cu(12)Sn(21)
      and K(12)Cu(12)Sn(21), DFT band structure calculations (TB-LMTO-ASA) reveal a
      band gap. The discrete [Sn@Cu(12)@Sn(20)](12-) cluster is analyzed in
      consideration of the molecular orbitals obtained from hybrid DFT calculations
      (Gaussian 09) for the cluster anion. The [Sn@Cu(12)@Sn(20)](12-) cluster MOs can
      be classified with labels indicating the numbers of radial and angular nodes, in
      the style of spherical shell models of cluster bonding.

PMID- 21961731
TI  - Maize microarray annotation database.
AB  - BACKGROUND: Microarray technology has matured over the past fifteen years into a
      cost-effective solution with established data analysis protocols for global gene
      expression profiling. The Agilent-016047 maize 44 K microarray was custom
      designed from EST sequences, but only reporter sequences with EST accession
      numbers are publicly available. The following information is lacking: (a)
      reporter - gene model match, (b) number of reporters per gene model, (c)
      potential for cross hybridization, (d) sense/antisense orientation of reporters,
      (e) position of reporter on B73 genome sequence (for eQTL studies), and (f)
      functional annotations of genes represented by reporters. To address this, we
      developed a strategy to annotate the Agilent-016047 maize microarray, and built a
      publicly accessible annotation database. DESCRIPTION: Genomic annotation of the
      42,034 reporters on the Agilent-016047 maize microarray was based on BLASTN
      results of the 60-mer reporter sequences and their corresponding ESTs against the
      maize B73 RefGen v2 "Working Gene Set" (WGS) predicted transcripts and the genome
      sequence. The agreement between the EST, WGS transcript and gDNA BLASTN results
      were used to assign the reporters into six genomic annotation groups. These
      annotation groups were: (i) "annotation by sense gene model" (23,668 reporters),
      (ii) "annotation by antisense gene model" (4,330); (iii) "annotation by gDNA"
      without a WGS transcript hit (1,549); (iv) "annotation by EST", in which case the
      EST from which the reporter was designed, but not the reporter itself, has a WGS
      transcript hit (3,390); (v) "ambiguous annotation" (2,608); and (vi)
      "inconclusive annotation" (6,489). Functional annotations of reporters were
      obtained by BLASTX and Blast2GO analysis of corresponding WGS transcripts against
      GenBank.The annotations are available in the Maize Microarray Annotation Database
      http://MaizeArrayAnnot.bi.up.ac.za/, as well as through a GBrowse annotation file
      that can be uploaded to the MaizeGDB genome browser as a custom track.The
      database was used to re-annotate lists of differentially expressed genes reported
      in case studies of published work using the Agilent-016047 maize microarray. Up
      to 85% of reporters in each list could be annotated with confidence by a single
      gene model, however up to 10% of reporters had ambiguous annotations. Overall,
      more than 57% of reporters gave a measurable signal in tissues as diverse as
      anthers and leaves. CONCLUSIONS: The Maize Microarray Annotation Database will
      assist users of the Agilent-016047 maize microarray in (i) refining gene lists
      for global expression analysis, and (ii) confirming the annotation of candidate
      genes before functional studies.

PMID- 21961733
TI  - Extending the range of neutral N-donor ligands available for metal catalysts: N
      [1-alkylpyridin-4(1H)-ylidene]amides in palladium-catalyzed cross-coupling
      reactions.
AB  - N-[1-Alkylpyridin-4(1H)-ylidene]amides (PYAs) are a new class of easily prepared,
      neutral N-donor ligands that share some features in common with N-heterocyclic
      carbenes. They are strongly electron-donating toward metal centers, and a
      palladium(II) complex of one of these ligands has been shown to successfully
      catalyze both the Heck-Mizoroki and Suzuki-Miyaura cross-coupling reactions.

PMID- 21961734
TI  - Associations between children's social functioning and physical activity
      participation are not mediated by social acceptance: a cross-sectional study.
AB  - BACKGROUND: Physical activity (PA) during childhood often occurs in social
      contexts. As such, children's ability to develop and maintain friendship groups
      may be important in understanding their PA. This paper investigates the
      associations among children's social functioning, and physical activity and
      whether perceptions of social acceptance mediate any social functioning-PA
      association. METHODS: A cross sectional survey in which 652 10-11 year olds self
      reported their peer (e.g. difficulties with friends) and conduct (e.g.
      anger/aggression) problems, prosocial behaviours (e.g. being kind to others) and
      perceptions of social acceptance. Physical activity was objectively assessed by
      Actigraph GT1M accelerometers to estimate counts per minute, (CPM) and minutes of
      moderate-to-vigorous physical activity (MVPA). Linear regression analyses were
      conducted to investigate associations between social functioning and PA. Indirect
      effects were analysed to explore mediation by social acceptance. RESULTS: Among
      boys, peer problems were negatively associated with CPM and MVPA and conduct
      problems were positively associated with CPM and MVPA. Prosocial behaviour was
      unrelated to PA in boys. Social functioning was not associated with PA among
      girls. Social acceptance did not mediate the social functioning-PA relationship.
      CONCLUSIONS: Boys' conduct and peer problems were associated positively and
      negatively respectively with their PA but this relationship was not mediated by
      perceptions of social acceptance. Future research should study alternative
      mediators to understand the processes underpinning this relationship.

PMID- 21961740
TI  - Words of wisdom. Re: Safety and feasibility of the prostatic urethral lift: a
      novel, minimally invasive treatment for lower urinary tract symptoms (LUTS)
      secondary to benign prostatic hyperplasia (BPH).

PMID- 21961741
TI  - Words of wisdom. Re: Adjuvant androgen deprivation for high-risk prostate cancer
      after radical prostatectomy: SWOG S9921 study.

PMID- 21961742
TI  - Words of wisdom. Re: The risks and benefits of 5alpha-reductase inhibitors for
      prostate-cancer prevention.

PMID- 21961743
TI  - Words of wisdom. Re: Antibody-based detection of ERG rearrangement-positive
      prostate cancer.

PMID- 21961744
TI  - Words of wisdom. Re: Human-specific loss of regulatory DNA and the evolution of
      human-specific traits.

PMID- 21961745
TI  - Words of wisdom. Re: Conventional-dose versus high-dose chemotherapy as first
      salvage treatment in male patients with metastatic germ cell tumors: evidence
      from a large international database. Re: Prognostic factors in patients with
      metastatic germ cell tumors who experienced treatment failure with cisplatin
      based first-line chemotherapy.

PMID- 21961746
TI  - Brazilian canine hepatozoonosis.
AB  - The genus Hepatozoon includes hundreds of species that infect birds, reptiles,
      amphibians and mammals, in all continents with tropical and subtropical climates.
      Two species have been described in domestic dogs: H. canis, reported in Europe,
      Asia, Africa, South America and the United States; and H. americanum, which so
      far has only been diagnosed in the United States. In Brazil, the only species
      found infecting dogs is H. canis. The objective of this review was to detail some
      aspects of canine hepatozoonosis, caused by H. canis, and the main points of its
      biology, transmission, pathogenicity, symptoms, epidemiology and diagnostic
      methods, with emphasis on research developed in Brazil.

PMID- 21961747
TI  - Perceptions and attitudes among milk producers in Minas Gerais regarding cattle
      tick biology and control.
AB  - This study evaluates milk producers' knowledge regarding cattle ticks and
      practices for controlling them. Ninety-three dairymen in Minas Gerais were
      interviewed. These producers had no information regarding acaricide efficiency
      tests. To analyze the information, open responses were categorized through
      "content analysis", and descriptive analysis consisting of extracting the profile
      highlighted by the highest frequencies. The association between schooling level
      and knowledge was tested by means of chi-square trend tests. It was observed that
      92.3% had no knowledge of the nonparasitic period. For 96.4%, what determined the
      time to apply treatment was the degree of tick infestation; 93.3% used spray guns
      to apply the acaricide. In seeking to cross-correlate the biological and control
      variables with education, cooperative action, length of experience and herd size,
      it was found that there was a linear association between schooling level and
      implementation of acaricide solution preparation. The other factors didn't show
      any significant association. These data demonstrated the need to instruct the
      producers in relation to the biology and control of Rhipicephalus (Boophilus)
      microplus. It was concluded that the majority of milk producers were unaware of
      cattle tick biology and the factors that influence choosing an acaricide, which
      makes it difficult to implement strategic control.

PMID- 21961748
TI  - Occurrence of antibodies against Neospora caninum and/or Toxoplasma gondii in
      dogs with neurological signs.
AB  - This study aimed to evaluate occurrences of antibodies against Neospora caninum
      and Toxoplasma gondii in dogs with neurological signs. Blood samples from 147
      dogs were collected: 127 from owned dogs (attended at the Veterinary Teaching
      Hospital of the Federal University of Parana (HV-UFPR) and at private veterinary
      clinics in the city of Curitiba), and 20 from stray dogs found in Curitiba's
      metropolitan region. The dogs presented one or more of the following neurological
      signs: seizures, paresis or paralysis, ataxia, behavioral abnormalities, sensory
      and somatic disorders and chorioretinitis. The samples were analyzed by means of
      the indirect fluorescent antibody test (IFAT), at a cutoff dilution of 1:50. Out
      of the 147 samples obtained, 17 (11.56%) were seropositive for N. caninum, 31
      (21.08%) for T. gondii and four (2.72%) for both protozoa. Serum titration on the
      positive animals showed that 54.83% (17/31) and 41.18% (7/17) had titers >= 1:200
      against T. gondii and N. caninum, respectively. A significant difference in
      seropositivity for T. gondii (P = 0.021; OR = 2.87; CI = 1.1 > 2.8 > 7.4) was
      observed between owned dogs (18.11%) and stray dogs (40%). Inclusion of
      serological tests for neosporosis and toxoplasmosis is recommended in diagnosing
      neurological diseases in dogs.

PMID- 21961749
TI  - Tissue alterations in the pirarucu, Arapaima gigas, infected by Goezia spinulosa
      (Nematoda).
AB  - Five specimens of Arapaima gigas caught in the Araguaia River (State of Mato
      Grosso, Brazil) were investigated for helminths in 2004. Numerous adult specimens
      of the rhapidascarid nematode Goezia spinulosa were found in stomach ulcers in
      all the specimens of A. gigas and were surrounded by thickening of the mucosa.
      The gastric glands of all the fish were necrotic and there was a severe and
      diffuse inflammatory reaction composed of eosinophils (which were predominant),
      lymphocytes and rare macrophages in the mucosa, submucosa and muscle layer. This
      is the first report of tissue lesion occurrences in this host, in the presence of
      G. spinulosa, and it confirms the high pathogenicity of this parasite species.

PMID- 21961750
TI  - Risk factors and clinical disorders of canine ehrlichiosis in the South of Bahia,
      Brazil.
AB  - The aim of this work was to study the clinical disorders and risk factors of
      canine ehrlichiosis in Ilheus and Itabuna, Bahia, and compare different
      diagnostic methods. Blood samples were collected from 200 dogs. Each dog was
      clinically examined. A questionnaire was used to evaluate the risk factors. The
      blood samples were analyzed using the Dot-ELISA test; hematometry, platelet
      counts and searches for morulae on blood smears were performed. Nested PCR was
      carried out on 50 serologically positive samples and 50 negative samples. Three
      positive PCRs were sequenced. Thirty-six percent were serologically positivity
      and 5.5% from blood smears. The animals were anemic and thrombocytopenic.
      Presence of ticks and living in areas on the urban periphery were considered to
      be risk factors (p < 0.05). Nested PCR identified 11 positive dogs of which nine
      were serologically positive and two were negative. The DNA sequencing was
      consistent with the presence of Ehrlichia canis.

PMID- 21961751
TI  - Effectiveness of Asteraceae extracts on Trichostrongylidae eggs development in
      sheep.
AB  - Data on in vitro evaluation of extracts of three species of the Asteraceae family
      on the development of Trichostrongylidae eggs in sheep are presented. Egg
      hatchability was tested using herbal extracts prepared in a Soxhlet extractor,
      and using hydrolate prepared by means of hydrodistillation. The laboratory tests
      showed that the ethanol extract from flowers of the species Aster lanceolatus
      presented high activity against Trichostrongylidae eggs development in sheep,
      inhibiting larva formation by 91% within 48 hours, and maintaining similar rates
      after 72 hours.

PMID- 21961752
TI  - Molecular and serological detection of Leishmania spp. in captive wild animals
      from Ilha Solteira, SP, Brazil.
AB  - Leishmaniasis is a zoonotic disease that affects 12 million people worldwide.
      Several mammalian species can serve as a reservoir for this disease. Dogs are the
      main reservoir for visceral leishmaniasis in urban areas, which has become a
      serious public health concern in Brazil. The aim of this study was to evaluate
      the presence of Leishmania spp. in captive wild animals from Ilha Solteira, Sao
      Paulo, Brazil. Blood and various tissues samples were collected from animals of
      five different species: Speothos venaticus, Chrysocyon brachyurus, Cerdocyon
      thous, Pseudalopex vetulus, and Procyon cancrivorus. Antibodies against
      Leishmania spp. were detected in three wild canids by indirect fluorescent
      antibody test (IFAT) and enzyme-linked immunosorbent assay (ELISA). PCR analyses
      of blood and bone marrow from all animals were negative, but Leishmania DNA was
      found in the tissues and skin of seropositive animals. Positive PCR samples were
      also positive for Leishmania donovani complex. Analysis of sequenced PCR products
      showed similarities with different regions of Leishmania (Leishmania) infantum
      and Leishmania (Leishmania) chagasi kinetoplastids. Measures to control visceral
      leishmaniasis in wild animals kept in Brazilian zoos should be established, as no
      disease control programs are currently available.

PMID- 21961753
TI  - Evaluation of Eucalyptus citriodora essential oil on goat gastrointestinal
      nematodes.
AB  - Phytotherapy may be an alternative strategy for controlling gastrointestinal
      parasites. This study evaluated the anthelmintic efficacy of Eucalyptus
      citriodora essential oil (EcEO). The in vitro effects of EcEO were determined
      through testing the inhibition of egg hatching and larval development of
      Haemonchus contortus. EcEO was subjected to acute toxicity testing on mice,
      orally and intraperitoneally. The in vivo effects of EcEO were determined by the
      fecal egg count reduction test (FECRT) in goats infected with gastrointestinal
      nematodes. The results showed that 5.3 mg.mL(-1) EcEO inhibited egg hatching by
      98.8% and 10.6 mg.mL(-1) EcEO inhibited H. contortus larval development by
      99.71%. The lethal doses for 50% of the mice were 4153 and 622.8 mg.kg(-1), for
      acute toxicity orally and intraperitoneally. In the FECRT, the efficacy of EcEO
      and ivermectin was 66.25 and 79.16% respectively, on goat gastrointestinal
      nematodes eight days after treatment. EcEO showed in vitro and in vivo
      anthelmintic activity.

PMID- 21961754
TI  - Phlebotomine sand flies and canine infection in areas of human visceral
      leishmaniasis, Cuiaba, Mato Grosso.
AB  - Visceral leishmaniasis is a systemic infectious disease that can cause to a
      severe, potentially life-threatening chronic condition in humans. Risk factors
      for infection in urban areas have been associated with poor living conditions,
      the presence of sand fly vectors and infected pets. This study aimed to describe
      sand fly and canine infection in the neighborhoods of human visceral
      leishmaniasis occurrence in the city of Cuiaba, Mato Grosso State, central
      western Brazil, reported between January 2005 and December 2006. A total of 1,909
      sand flies were collected. They were predominantly males and the most frequent
      species were Lutzomyia cruzi (81.25%), Lutzomyia whitmani (13.88%) and Lutzomyia
      longipalpis (2.62%). The sand fly density was not significantly correlated with
      the variation of environmental factors. The prevalence of canine visceral
      leishmaniasis in the neighborhoods studied was 26.82% and it was found that areas
      with high density of vectors coincided with areas of high prevalence of dogs and
      those with the highest rates of human cases. The study of vectors and other
      potential hosts are essential for a good understanding of visceral leishmaniasis
      and the related public health concerns, aiming at the prevention and control of
      leishmaniasis in the city of Cuiaba, Mato Grosso State.

PMID- 21961755
TI  - Factors associated to Theileria equi in equids of two microregions from Rio de
      Janeiro, Brazil.
AB  - Serum samples from 714 equids of Itaguai and Serrana microregions, Rio de
      Janeiro, southeastern Brazil, were examined by indirect fluorescent antibody test
      (titer 1:80) for Theileria equi. The prevalence in the microregions and factors
      associated with seropositivity were evaluated and the prevalence ratio (PR)
      calculated. The overall prevalence of T. equi infection was 81.09% (n = 579),
      with higher prevalence (p < 0.05) in the Itaguai (85.43%) when compared to
      Serrana microregion (76.92%). The geographic area, altitude, farming condition
      and area of origin of equids were associated (p < 0.05) with seropositivity for
      T. equi. Equids reared in the Itaguai microregion (PR = 1.11, p = 0.003) and at
      altitudes below 500 m (PR = 1.10; p = 0,014) were more likely to be seropositive
      for T. equi. Furthermore, when equids were born in the farm (PR = 1.10, p =
      0.008) and reared with poor farming conditions (PR = 1.13, p = 0.018) they were
      more likely to be exposed to T. equi. The main ticks found on equids were
      Amblyomma cajennense and Dermacentor (Anocentor) nitens. The microregions studied
      are endemic areas for equine theileriosis and there exists enzootic stability for
      T. equi. Only factors related to the collection area of serum samples influenced
      the seropositivity of equids for T. equi in that region.

PMID- 21961756
TI  - Compromised nutrition in gerbils infected by Cystoisospora felis detected through
      an animal performance analysis tool.
AB  - The impact of Cystoisospora felis infection on the nutritional efficiency of
      gerbils was studied. The variables weight gain and feed intake were measured
      during four weeks in 28 laboratory gerbils, of which 14 were inoculated with 3.5
      * 10(5) sporulated oocysts of C. felis and the remaining 14 were controls. The
      animals from both groups were weighted, killed, eviscerated and had their
      carcasses and tissues weighted and compared. A modern tool designed for measuring
      nutritional performance of farm animals was applied. The results showed
      compromised nutritional efficiency of the infected animals within the first week
      after infection. The consequences of these results are discussed here, including
      the potential impact of infection on farm animals performance.

PMID- 21961757
TI  - Serological survey of Neospora caninum in small ruminants from Pernambuco State,
      Brazil.
AB  - Neospora caninum infection is an important cause of bovine abortion as well as
      neonatal mortality in goats and sheep. A serological survey for antibodies
      against N. caninum in goats and sheep was carried out in the municipality of
      Ibimirim, PE, Northeastern Brazil. The imunnofluoresce antibody test showed that
      26.6% (85/319) of the goats and 64.2% (52/81) of the sheep were positive.
      Serologic reactivity was associated with age in goats (p < 0.01) and sheep (p >
      0.05), with increasing rates in older animals. These results indicate exposure to
      N. caninum among small ruminants in the study area.

PMID- 21961758
TI  - Coccidiosis in broiler chickens raised in the Araguaina region, State of
      Tocantins, Brazil.
AB  - Eimeriosis is responsible for causing serious problems in poultry, mainly
      characterized by reduced weight gain and abnormalities of food conversion
      efficiency, thereby causing great economic losses. The aim of this study was to
      evaluate the epidemiology of eimeriosis in broiler chickens in the Araguaina
      region, State of Tocantins, Brazil. Samples from five farm properties were
      collected and sent to the Hygiene and Public Health Laboratory, School of
      Veterinary Medicine and Zootechnics, Federal University of Tocantins. From the
      parasitological analysis, it was shown that all the properties examined were
      positive for Eimeria species. 63.1% of the sheds were positive, with findings of
      oocysts of E. maxima, E. acervulina, E. mitis and E. tenella. It was concluded
      that all properties evaluated were positive for four species of the genus
      Eimeria, thus demonstrating that the sanitary strategies followed in poultry
      rearing had flaws that allowed pathogens to spread in poultry pens.

PMID- 21961759
TI  - Molecular detection of Hepatozoon canis and Babesia canis vogeli in domestic dogs
      from Cuiaba, Brazil.
AB  - The objective of this study was to report for the first time infection by
      Hepatozoon spp. and Babesia spp. in 10 dogs from the city of Cuiaba, State of
      Mato Grosso, central-western Brazil. A pair of primers that amplifies a 574 bp
      fragment of the 18S rRNA of Hepatozoon spp., and a pair of primers that amplifies
      a 551 bp fragment of the gene 18S rRNA for Babesia spp. were used. Six dogs were
      positive for Babesia spp., and 9 were positive for Hepatozoon spp. Co-infection
      of Babesia spp. and Hepatozoon spp. was seen in 5 dogs. Sequenced samples
      revealed 100% identity with B. canis vogeli, and H. canis. This is the first
      molecular detection of H. canis in domestic dogs from Cuiaba. Additionally, it is
      described for the first time the presence of B. canis vogeli circulating among
      dogs in Cuiaba.

PMID- 21961760
TI  - Seroprevalence of Toxoplasma gondii infection in cats from Curitiba, Parana,
      Brazil.
AB  - Toxoplasmosis is a worldwide zoonosis caused by the protozoa Toxoplasma gondii
      which infects all warm-blood vertebrates. This study aimed to assess the
      seroprevalence of anti-Toxoplasma gondii antibodies in a population of domestic
      cats seen at a major cat-only veterinary clinic in Curitiba, Parana State,
      Southern Brazil. Serum samples were processed by indirect immunofluorescence
      assay (IIFA) for the detection of IgG. Antibody titers were found in 16.3%
      (46/282) of sera analyzed, with titers to T. gondii of 16 in eight cats, 64 in 23
      cats, 256 in 14 cats and 1024 in one cat. Statistical differences were not found
      regarding the association with age, gender and different areas of the city (p >
      0.05). No significant differences were found in any variable when comparing
      seropositivity with potential risk factors. The seroprevalence was relatively
      lower when compared to other Brazilian regions, probably due to the fact that the
      cats studied were owned, domiciled with restricted dietary habits based on
      processed foods, restricted access to the street and no prey access. In
      conclusion, low feline toxoplasmosis seroprevalence may be associated to owned
      cats due to adequate dietary care and restricted outdoor access, as well as low
      local environmental exposure.

PMID- 21961761
TI  - Parasite meningomyelitis in cats in Uruguay.
AB  - Two outbreaks of progressive hind limb paresis in cats (Felis catus) caused by
      parasitic meningomyelitis in Uruguay are reported. The case studies occurred in
      2008 and 2009 respectively, in the rural areas of Fray Bentos (33 degrees  07'
      40.39'' S) and were characterized by hindquarter paralysis. This paralysis was
      progressive and had a chronic progression of approximately 12 months until the
      death or euthanasia of the animals. Clinical symptoms started with ataxia of the
      hindquarters with lateral side-to-side swaying and culminated in total paralysis.
      Two animals were sent for necropsy in 2009. The main histopathological findings
      were severe myelitis in the lumbar spinal cord with perivascular cuffing and
      white matter necrosis, severe nonsuppurative meningitis with thrombi in
      subarachnoid blood vessels, and intravascular presence of multiple adult
      parasites. From the morphological characteristics of the parasites and location
      in the leptomeninges, the parasite was identified as the nematode Gurltia
      paralysans.

PMID- 21961762
TI  - Tactile massage and hypnosis as a health promotion for nurses in emergency care-
      a qualitative study.
AB  - BACKGROUND: This study explores nursing personnel's experiences and perceptions
      of receiving tactile massage and hypnosis during a personnel health promotion
      project. Nursing in a short term emergency ward environment can be emotionally
      and physically exhausting due to the stressful work environment and the high
      dependency patient care. A health promotion project integrating tactile massage
      and hypnosis with conventional physical activities was therefore introduced for
      nursing personnel working in this setting at a large university hospital in
      Sweden. METHODS: Four semi-structured focus group discussions were conducted with
      volunteer nursing personnel participants after the health promotion project had
      been completed. There were 16 participants in the focus groups and there were 57
      in the health promotion intervention. The discussions were transcribed verbatim
      and analysed with qualitative content analysis. RESULTS: The findings indicated
      that tactile massage and hypnosis may contribute to reduced levels of stress and
      pain and increase work ability for some nursing personnel. The sense of well
      being obtained in relation to health promotion intervention with tactile massage
      and hypnosis seemed to have positive implications for both work and leisure. Self
      awareness, contentment and self-control may be contributing factors related to
      engaging in tactile massage and hypnosis that might help nursing personnel
      understand their patients and colleagues and helped them deal with difficult
      situations that occurred during their working hours. CONCLUSION: The findings
      indicate that the integration of tactile massage and hypnosis in personnel health
      promotion may be valuable stress management options in addition to conventional
      physical activities.

PMID- 21961763
TI  - A multi-centre, randomised controlled trial of cognitive therapy to prevent
      harmful compliance with command hallucinations.
AB  - BACKGROUND: Command hallucinations are among the most distressing, high risk and
      treatment resistant symptoms for people with psychosis; however, currently, there
      are no evidence-based treatment options available for this group. A cognitive
      therapy grounded in the principles of the Social Rank Theory, is being evaluated
      in terms of its effectiveness in reducing harmful compliance with command
      hallucinations. METHODS/DESIGN: This is a single blind, intention-to-treat, multi
      centre, randomized controlled trial comparing Cognitive Therapy for Command
      Hallucinations + Treatment as Usual with Treatment as Usual alone. Eligible
      participants have to fulfil the following inclusion criteria: i) >=16 years; ii)
      ICD-10 diagnosis of schizophrenia or related disorder; iii) command
      hallucinations for at least 6 months leading to risk of harm to self or others.
      Following the completion of baseline assessments, eligible participants will be
      randomly allocated to either the Cognitive Therapy for Command Hallucinations +
      Treatment as Usual group or the Treatment as Usual group. Outcome will be
      assessed at 9 and 18 months post randomization with assessors blind to treatment
      allocation. The primary outcome is compliance behaviour and secondary outcomes
      include beliefs about voices' power, distress, psychotic symptoms together with a
      health economic evaluation. Qualitative interviews with services users will
      explore the acceptability of Cognitive Therapy for Command Hallucinations.
      DISCUSSION: Cognitive behaviour therapy is recommended for people with psychosis;
      however, its focus and evaluation has primarily revolved around the reduction of
      psychotic symptoms. In this trial, however, the focus of the cognitive
      behavioural intervention is on individuals' appraisals, behaviour and affect and
      not necessarily symptoms; this is also reflected in the outcome measures used. If
      successful, the results will mark a significant breakthrough in the evidence base
      for service users and clinicians and will provide a treatment option for this
      group where none currently exist. The trial will open the way for further
      breakthrough work with the 'high risk' population of individuals with psychosis,
      which we would intend to pursue. TRIAL REGISTRATION: ISRCTN: ISRCTN62304114.

PMID- 21961764
TI  - Rubinstein-Taybi syndrome with scoliosis.
AB  - STUDY DESIGN: Case report. OBJECTIVE: The authors present the case of a 14-year
      old boy with Rubinstein-Taybi syndrome (RSTS) presenting scoliosis. SUMMARY OF
      BACKGROUND DATA: There have been no reports on surgery for RSTS presenting
      scoliosis. METHODS: The patient was referred to our hospital for evaluation of a
      progressive spinal curvature. A standing anteroposterior spine radiograph at
      presentation to our hospital revealed an 84-degree right thoracic curve from T6
      to T12, along with a 63-degree left lumbar compensatory curve from T12 to L4. We
      planned a two-staged surgery and decided to fuse from T4 to L4. The first
      operation was front-back surgery because of the rigidity of the right thoracic
      curve. The second operation of lumbar anterior discectomy and fusion was arranged
      9 months after the first surgery to prevent the crankshaft phenomenon due to his
      natural course of adolescent growth. To avoid respiratory complications, the
      patient was put on a respirator in the ICU for several days after both surgeries.
      RESULTS: Full-length spine radiographs after the first surgery revealed no
      instrumentation failure and showed that the right thoracic curve was corrected to
      31 degrees and the left lumbar curve was corrected to 34 degrees. No
      postoperative complications occurred after both surgeries. CONCLUSIONS: We
      succeeded in treating the patient without complications. Full-length spine
      standing radiographs at one year after the second operation demonstrated a stable
      bony arthrodesis with no loss of initial correction.

PMID- 21961765
TI  - Sedimentation and resuspendability evaluation of pharmaceutical suspensions by
      low-field one dimensional pulsed field gradient NMR profilometry.
AB  - In order to study the sedimentation of pharmaceutical suspensions using low-field
      one dimensional pulsed field gradient nuclear magnetic resonance (1D pfg NMR)
      profilometry, the accuracy of signal acquisition as well as the spatial
      resolution of a commercial spectrometer operating at 23.4 MHz was investigated.
      The use of a solid Teflon spacer revealed that the accuracy of signal acquisition
      was independent of spatial position (height). The standard deviation of distance
      determinations was less than 150 um, whereas the accuracy of water content
      determination was within 2% in the central part of the detection zone and
      deteriorated to 4% in the outer parts. The study of aqueous paramagnetic MnCl2
      solutions indicated an exponential relationship between the relative signal
      intensity and the transverse relaxation decay constant. From this relationship,
      the relative water content of suspensions could be derived from their signal
      intensity relative to that of water. Using concentrated paliperidone palmitate
      dispersions as model suspensions, low-field 1D pfg NMR profilometry has been
      proven to be suitable for the evaluation of both the sedimentation and
      resuspendability behavior of viscous, opaque suspensions, for which visual
      detection of homogeneity may be difficult.

PMID- 21961766
TI  - Prognosis value of the blood transaminase in acute ischaemic stroke: gender
      factors should be considered.

PMID- 21961767
TI  - In this issue/abstract thinking: is there a place for complementary and
      alternative medicine in child psychiatry?

PMID- 21961768
TI  - Promover el bilinguismo: American children should learn Spanish, and so should
      American child psychiatrists.

PMID- 21961769
TI  - Trying to predict the future of a nascent discipline: whaddya got?

PMID- 21961770
TI  - Fish oil is not snake oil.

PMID- 21961771
TI  - DSM-10: coming soon to a psychiatric practice near you.

PMID- 21961772
TI  - Out of the funhouse mirrors: steps toward understanding the role of parenting in
      maladaptive child development.

PMID- 21961773
TI  - Cardiovascular risk of stimulant treatment in pediatric attention
      deficit/hyperactivity disorder: update and clinical recommendations.
AB  - OBJECTIVE: This review provides an update on the cardiovascular impact of
      therapeutic stimulant-class medication for children and adolescents with
      attention-deficit/hyperactivity disorder (ADHD). METHOD: Relevant clinical
      literature was ascertained using PubMed searches limited to human studies and the
      English language as of May 2011. Current practice guidelines and consensus
      statements also were reviewed. RESULTS: Stimulant-class medications for healthy
      children and adolescents with ADHD are associated with mean elevations in blood
      pressure (<=5 mmHg) and heart rate (<=10 beats/min) without changes in
      electrocardiographic parameters. A subset (5-15%) of children and adolescents
      treated may have a greater increase in heart rate or blood pressure at a given
      assessment or may report a cardiovascular-type complaint during stimulant
      treatment. It is extremely rare for a child or adolescent receiving stimulant
      medication to have a serious cardiovascular event during treatment, with the risk
      appearing similar to groups of children not receiving stimulant medication.
      CONCLUSIONS: Clinicians should adhere to current recommendations regarding the
      prescription of stimulant medications for youth with ADHD. Scientific inquiry is
      indicated to identify patients at heightened risk and to continue surveillance
      for the longer-term cardiovascular impact of these agents.

PMID- 21961774
TI  - Omega-3 fatty acid supplementation for the treatment of children with attention
      deficit/hyperactivity disorder symptomatology: systematic review and meta
      analysis.
AB  - OBJECTIVE: Several studies have demonstrated differences in omega-3 fatty acid
      composition in plasma and in erythrocyte membranes in patients with attention
      deficit/hyperactivity disorder (ADHD) compared with unaffected controls. Omega-3
      fatty acids have anti-inflammatory properties and can alter central nervous
      system cell membrane fluidity and phospholipid composition. Cell membrane
      fluidity can alter serotonin and dopamine neurotransmission. The goal of this
      meta-analysis was to examine the efficacy of omega-3 fatty acid supplementation
      in children with ADHD. METHOD: PubMed was searched for randomized placebo
      controlled trials examining omega-3 fatty acid supplementation in children with
      ADHD symptomatology. The primary outcome measurement was standardized mean
      difference in rating scales of ADHD severity. Secondary analyses were conducted
      to determine the effects of dosing of different omega-3 fatty acids in
      supplements. RESULTS: Ten trials involving 699 children were included in this
      meta-analysis. Omega-3 fatty acid supplementation demonstrated a small but
      significant effect in improving ADHD symptoms. Eicosapentaenoic acid dose within
      supplements was significantly correlated with supplement efficacy. No evidence of
      publication bias or heterogeneity between trials was found. CONCLUSION: Omega-3
      fatty acid supplementation, particularly with higher doses of eicosapentaenoic
      acid, was modestly effective in the treatment of ADHD. The relative efficacy of
      omega-3 fatty acid supplementation was modest compared with currently available
      pharmacotherapies for ADHD such as psychostimulants, atomoxetine, or alpha(2)
      agonists. However, given its relatively benign side-effect profile and evidence
      of modest efficacy, it may be reasonable to use omega-3 fatty supplementation to
      augment traditional pharmacologic interventions or for families who decline other
      psychopharmacologic options.

PMID- 21961775
TI  - Course of subthreshold bipolar disorder in youth: diagnostic progression from
      bipolar disorder not otherwise specified.
AB  - OBJECTIVE: To determine the rate of diagnostic conversion from an operationalized
      diagnosis of bipolar disorder not otherwise specified (BP-NOS) to bipolar I
      disorder (BP-I) or bipolar II disorder (BP-II) in youth over prospective follow
      up and to identify factors associated with conversion. METHOD: Subjects were 140
      children and adolescents recruited from clinical referrals or advertisement who
      met operationalized criteria for BP-NOS at intake and participated in at least
      one follow-up evaluation (91% of initial cohort). Diagnoses were assessed at
      follow-up interviews using the Longitudinal Interval Follow-Up Evaluation. The
      mean duration of follow-up was 5 years and the mean interval between assessments
      was 8.2 months. RESULTS: Diagnostic conversion to BP-I or BP-II occurred in 63
      subjects (45%): 32 (23%) to BP-I (nine of whom had initially converted to BP-II)
      and 31 to only BP-II (22%). Median time from intake to conversion was 58 weeks.
      First- or second-degree family history of mania or hypomania was the strongest
      baseline predictor of diagnostic conversion (p = .006). Over follow-up,
      conversion was associated with greater intensity of hypomanic symptoms and with
      greater exposure to specialized, intensive outpatient psychosocial treatments.
      There was no association between conversion and exposure to treatment with
      particular medication classes. CONCLUSIONS: Children and adolescents referred
      with mood symptoms that meet operationalized criteria for BP-NOS, particularly
      those with a family history of BP, frequently progress to BP-I or BP-II. Efforts
      to identify these youth and effectively intervene may have the potential to
      curtail the progression of mood disorders in this high-risk population.

PMID- 21961776
TI  - Progression of amygdala volumetric abnormalities in adolescents after their first
      manic episode.
AB  - OBJECTIVE: Although previous neuroimaging studies suggest that adolescents with
      bipolar disorder exhibit smaller amygdala volumes compared with healthy
      adolescents, whether these abnormalities are present at illness onset or instead
      develop over time remains unclear. The aim of this study was to conduct a
      prospective longitudinal investigation comparing amygdala neurodevelopment among
      adolescents after their first manic episode, adolescents with attention
      deficit/hyperactivity disorder (ADHD), and healthy adolescents. METHOD: A total
      of 30 adolescents hospitalized for their first manic/mixed episode associated
      with bipolar disorder, 29 adolescents with ADHD, and 24 demographically matched
      healthy teens underwent magnetic resonance imaging scanning at index assessment
      and approximately 12 months later. Adolescents with bipolar disorder were
      prospectively evaluated using diagnostic interviews and with symptom rating
      scales. RESULTS: Mixed models examining the group * time effect for both left (p
      = .005) and right (p = .002) amygdala volumes were statistically significant.
      Change in left (p = .01) and right (p = .0008) amygdala volumes from baseline to
      12 months were significantly different among groups. Specifically, left amygdala
      volumes increased over time in healthy adolescents (p = .008) and adolescents
      with ADHD (p = .0009), but not in adolescents with bipolar disorder (p = .3).
      Right amygdala volume increased over time in adolescents with ADHD (p < .001),
      but not in healthy adolescents nor in adolescents with bipolar disorder (p = .1
      and p = .3, respectively). In adolescents with bipolar disorder, baseline total
      amygdala volume was significantly greater in those who subsequently achieved
      symptomatic recovery as compared with those who did not achieve recovery (p =
      .02). CONCLUSIONS: Adolescents with mania do not exhibit normal increases in
      amygdala volume that occur during healthy adolescent neurodevelopment.

PMID- 21961777
TI  - Functional connectivity of the amygdala in early-childhood-onset depression.
AB  - OBJECTIVE: Adult major depressive disorder (MDD) is associated with reduced
      cortico-limbic functional connectivity thought to indicate decreased top-down
      control of emotion. However, it is unclear whether such connectivity alterations
      are also present in early-childhood-onset MDD. METHOD: A total of 51 children 7
      through 11 years of age who had been prospectively studied since preschool age,
      completed resting state functional magnetic resonance imaging (fMRI) and were
      assigned to one of four groups: 1) C-MDD (N = 13), those children with a personal
      history of early-childhood-onset MDD; 2) M-MDD (N = 11), those with a maternal
      history of affective disorders; 3) CM-MDD (N = 13), those with both maternal and
      early-childhood-onset MDD; or 4) CON (N = 14), those without either a personal or
      maternal history of MDD. We used seed-based resting state functional connectivity
      (rsfcMRI) analysis in an independent sample of adults to identify networks
      showing both positive (e.g., limbic regions) and negative (e.g., dorsal
      frontal/parietal regions) connectivity with the amygdala. These regions were then
      used in region-of-interest-based analyses of our child sample. RESULTS: We found
      a significant interaction between maternal affective disorder history and the
      child's MDD history for both positive and negative rsfcMRI networks.
      Specifically, when compared with CON, we found reduced connectivity between the
      amygdala and the "negative network" in children with C-MDD, M-MDD, and CM-MDD.
      Children with either C-MDD or a maternal history of MDD (but not CM-MDD)
      displayed reduced connectivity between the amygdala and the "positive network."
      CONCLUSIONS: Our finding of an attenuated relationship between the amygdala, a
      region affected in MDD and involved in emotion processing, and cognitive control
      regions is consistent with a hypothesis of altered regulation of emotional
      processing in C-MDD, suggesting developmental continuity of this alteration into
      early childhood.

PMID- 21961778
TI  - Disentangling child and family influences on maternal expressed emotion toward
      children with attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: We used multi-level modelling of sibling-pair data to disentangle the
      influence of proband-specific and more general family influences on maternal
      expressed emotion (MEE) toward children and adolescents with attention
      deficit/hyperactivity disorder (ADHD). METHOD: MEE was measured using the Five
      Minute Speech Sample (FMSS) for 60 sibling pairs (aged 5 through 17 years) each
      comprising one proband with ADHD and one child without ADHD. Questionnaire
      measures were used to assess child and adolescent conduct and emotional problems
      and maternal depression and ADHD. Multi-level models partitioned the effects of
      five MEE components (initial statement [IS], relationship [REL], warmth [WAR],
      critical comments [CC], and positive comments [PC]) into proband-specific and
      general family effects. RESULTS: Significant proband-specific effects were
      confirmed for all MEE components, with higher levels of MEE expressed toward
      probands with ADHD than siblings without ADHD. For REL, PC, and CC, this effect
      was explained by comorbid child conduct problems rather than ADHD. Only low WAR
      was associated with child ADHD itself. Furthermore, only low WAR was related to
      variations in more general family characteristics, especially levels of maternal
      depression. CONCLUSIONS: MEE toward children with ADHD was influenced by proband
      specific factors. For most components, these were driven by comorbid symptoms of
      conduct problems rather than ADHD itself. WAR was different; it was influenced by
      both child-specific and more general characteristics of the family. Further
      studies utilising a longitudinal design are required to establish the direction
      of causation and extend our understanding of the relationship between EE
      components and ADHD.

PMID- 21961779
TI  - Child psychopathic traits moderate relationships between parental affect and
      child aggression.
AB  - OBJECTIVE: Previous studies show that children with psychopathic traits may be
      less responsive to parenting. Although harsh/inconsistent parenting is associated
      with increased problem behaviors in children low on psychopathic traits, children
      high on psychopathic traits show consistently high levels of problem behavior
      regardless of negative parenting. Moderating effects of child psychopathic traits
      on positive dimensions of parenting have not been explored. METHOD: We applied
      multi-level regression models to test for interactions between child psychopathic
      traits and both positive and negative parental affect on individual differences
      in both reactive and proactive aggression, in a community-based sample of 1,158
      children aged 9 through 10 years of age. RESULTS: There were significant
      associations between child psychopathic traits and positive and negative parental
      affect with both forms of aggression. Child psychopathic traits also moderated
      effects of positive and negative parental affect. Children low on psychopathic
      traits showed decreasing reactive aggression as positive parental affect
      increased, and increasing levels of reactive aggression as negative parental
      affect increased, but children high on psychopathic traits showed more stable
      levels of reactive aggression regardless of levels of parental affect. Proactive
      aggression was more strongly associated with negative parental affect among
      children with higher levels of psychopathic traits. CONCLUSIONS: In a community
      sample of preadolescent children, child psychopathic traits were shown to
      moderate the effects of parental affect on aggression. Reactive aggression in
      children high on psychopathic traits appears less responsive to variations in
      either positive or negative parenting. In contrast, child psychopathic traits may
      exacerbate the effects of high levels of negative parental effect on proactive
      aggression.

PMID- 21961781
TI  - Measuring adherence in TORDIA.

PMID- 21961780
TI  - Safe Thinking and Affect Regulation (STAR): human immunodeficiency virus
      prevention in alternative/therapeutic schools.
AB  - OBJECTIVE: To evaluate the effectiveness of Safe Thinking and Affect Regulation
      (STAR), a 14-session HIV-prevention program for adolescents at
      alternative/therapeutic schools. Because these youth frequently have difficulties
      with emotions and cognitions, it was designed to improve sexuality-specific
      affect management and cognitive monitoring, as well as HIV-related knowledge and
      attitudes. It was hypothesized that STAR would lead to a decrease in sexual risk
      and improved HIV knowledge and attitudes. METHOD: Fourteen schools were randomly
      assigned by year either to the STAR intervention or a brief educational program.
      Schools received the alternate intervention the following year. A total of 185
      adolescents in 29 cohorts (groups) participated in the interventions. Assessment
      of sexual behavior, knowledge and attitudes with audio computer-assisted self
      interviews occurred at 3, 6, and 9 months post intervention. RESULTS:
      Hierarchical linear model (HLM) analyses found that adolescents in the STAR
      intervention reported a significantly greater decrease (p < .05) in the Sexual
      Risk Index than youth in the control group over the 6 months post intervention
      and similar improvements in the HIV Knowledge Scale and the Condom Use Self
      Efficacy Scale. There were no group differences between 6 and 9 months post
      intervention. CONCLUSIONS: This STAR intervention for youth in alternative
      schools was associated with decreased sexual risk for 6 months after the
      intervention. These data suggest that intervention strategies that target
      cognitions and affect within a sexual context might be usefully applied to
      improving sexual behavior but may need to be reinforced over time. Clinical trial
      registration information--HIV, Abuse, and Psychiatric Disorders Among Youth;
      http://clinicaltrials.gov; NCT00603369.

PMID- 21961783
TI  - Measuring adherence in TORDIA.

PMID- 21961785
TI  - The interpretation of low mood and worry by high users of secondary care with
      medically unexplained symptoms.
AB  - BACKGROUND: Around 1% of adults are repeatedly referred from primary to secondary
      care with medically unexplained symptoms (MUS); many of these patients have
      depression and anxiety disorders which are unrecognized or inadequately treated.
      We aimed to investigate the ways patients with MUS and their General
      Practitioners (GPs) interpret low mood and worry, whether they regard them as
      depressive or anxiety disorders and how they relate them causally to symptoms.
      METHODS: We carried out semi-structured interviews with 27 patients who had been
      repeatedly referred to specialists for MUS and their GPs and analysed transcripts
      by qualitative comparison. The analysis examined themes relating to low mood and
      worry, and their influence on symptoms. It drew on the concept of "otherness",
      whereby mental phenomena can be located either within the self or as separate
      entities. RESULTS: Both patients and GPs acknowledged the presence of low mood
      and worry. They viewed low mood as either an individual's personal response to
      circumstances (including their physical symptoms) or as the illness called
      "depression"; only the latter was amenable to medical intervention. Worry was
      seen as a trait rather than as a symptom of an anxiety disorder. While low mood
      and worry were acknowledged to influence physical symptoms, they were considered
      insufficient to be the main cause by either the patients or their doctors.
      CONCLUSIONS: Patients with MUS who are high users of secondary care services
      interpret low mood and worry in ways which allow them to be discussed with
      professionals, but not as the cause of their physical symptoms.

PMID- 21961786
TI  - Band-edge exciton fine structure of small, nearly spherical colloidal CdSe/ZnS
      quantum dots.
AB  - The exciton fine structure of small (2-3.5 nm) wurtzite (WZ) and zincblende (ZB)
      CdSe quantum dots (Qdots) has been investigated by means of nanosecond and
      picosecond time-resolved photoluminescence spectroscopy, at temperatures ranging
      from 5 K to room temperature. For both crystal structures, we observe a similar
      dark-bright energy level splitting of 2.4-5 meV, with a larger splitting
      corresponding to smaller Qdots. In addition, spectrally resolved streak camera
      images collected at 5 K reveal the presence of a third state, split from the
      lower dark-bright manifold by 30-70 meV, again independently of the crystal
      structure of the Qdots. The data thus reveal that small WZ and ZB CdSe Qdots are
      optically indistinguishable. This contrasts with theoretical calculations within
      the effective-mass approximation, which, in the limit of spherical Qdots, yield a
      different fine structure for both. However, experimental and theoretical results
      converge when taking the Qdot shape into account. With transmission electron
      microscopy, we determined that our Qdots are prolate, with an aspect ratio of
      1.15:1. Incorporating this value into our calculations, we obtain a similar fine
      structure for both WZ and ZB Qdots. Moreover, the opposite sign of the crystal
      field and shape anisotropy in CdSe suggests that the lowest energy level in small
      CdSe Qdots has an angular momentum projection F = 0, in contrast with (perfectly)
      spherical Qdots, where the lowest level corresponds to the dark +/-2 state. From
      the experimental and theoretical data we conclude that shape anisotropy and
      exchange interactions dominate over the crystal field anisotropy-induced
      splitting in this size range.

PMID- 21961787
TI  - Sensitive detection of Bacillus anthracis spores by immunocapture and liquid
      chromatography-tandem mass spectrometry.
AB  - Bacillus anthracis  is one of the most dangerous agents of the bioterrorism
      threat. We present here a sensitive immuno-liquid chromatography-tandem mass
      spectrometry (immuno-LC-MS/MS) approach to spore detection in complex
      environmental samples. It is based on the combined specificity and sensitivity of
      two techniques: immunocapture and targeted mass spectrometry. The immunocapture
      step, realized directly on the intact spores, is essential for their selective
      isolation and concentration from complex environmental samples. After parallel
      trypsin and Glu-C digestions, proteotypic peptides corresponding to small acid
      soluble spore protein-B (SASP-B) are specifically monitored in the multiple
      reaction monitoring (MRM) mass spectrometry mode. Peptide ratio is carefully
      monitored and provides an additional level of specificity, which is shown to be
      highly useful for distinguishing closely related samples and avoiding false
      positive/negative results. Sensitivity at the level of the infectious dose is
      demonstrated, with limits of detection of 7 * 10(3) spores/mL of milk or 10 mg of
      soil. This mass spectrometry approach is thus complementary to polymerase chain
      reaction (PCR) techniques.

PMID- 21961793
TI  - Photooxidation of chloride by oxide minerals: implications for perchlorate on
      Mars.
AB  - We show that highly oxidizing valence band holes, produced by ultraviolet (UV)
      illumination of naturally occurring semiconducting minerals, are capable of
      oxidizing chloride ion to perchlorate in aqueous solutions at higher rates than
      other known natural perchlorate production processes. Our results support an
      alternative to atmospheric reactions leading to the formation of high
      concentrations of perchlorate on Mars.

PMID- 21961794
TI  - Use of osteoporosis drugs in patients with recent-onset rheumatoid arthritis in
      Finland.
AB  - OBJECTIVES: We investigated the implementation of pharmaceutical osteoporosis
      (OP) prevention in early rheumatoid arthritis (RA) in Finland. METHODS: All
      incident RA cases from 2000 to 2007 were identified using the national register
      of the Social Insurance Institution (SII) as the sole source. The use of calcium
      and vitamin D preparations and OP drugs during the first year was evaluated.
      RESULTS: A total of 14,878 incident RA patients were found. They had a mean age
      of 56 (SD 15) and 68% were female. Nine per cent of the total number, which
      equated to 11% for women and to 5% men, had purchased OP drugs. The use of OP
      drugs increased over time: in the 2006-2007 period, relative risk (RR) for
      purchase was 1.62 (95% CI 1.38-1.92) for women and 2.1 (1.34-3.30) for men
      compared to the 2000-2001 period. Over the 2000-2005 period, 49% of females and
      52% of males used glucocorticoids (GCs) during the first year. Among the GC
      users, 38% of women and 24% of men also received calcium and vitamin D
      preparations by prescription, and 14% of women and 6% of men also used OP drugs.
      For GC users, the female sex, and older age increased the risk for OP use: the
      respective RRs were 1.45 (95% CI 1.31-1.61), 2.54 (95% CI 2.21-2.91), and 1.060
      (95% CI 1.057-1.065). CONCLUSIONS: Patients with early RA are increasingly
      receiving OP drugs, and the use is more frequent among patients with known risk
      factors.

PMID- 21961795
TI  - Adolescent predictors of objectively measured physical activity and sedentary
      behaviour at age 42: the Amsterdam Growth and Health Longitudinal Study (AGAHLS).
AB  - BACKGROUND: This study investigated the associations of physical characteristics
      and personality in adolescence with physical activity and sedentary behaviour in
      adulthood. FINDINGS: Physical characteristics (i.e. objectively measured BMI, sum
      of skin folds, MOPER test battery performance), and personality (i.e. self
      reported inadequacy, social inadequacy, rigidity, self-sufficiency/recalcitrance,
      dominance, achievement motivation, facilitating anxiety, debilitating anxiety,
      and social desirability) were assessed in 217 adolescent boys (Mean 13.0, SD 0.6)
      and girls (Mean 12.9, SD 0.6). Twenty-nine years later, at the age of 42, their
      physical activity and sedentary behaviour were assessed by means of
      accelerometry. Boys who scored lower on self-sufficiency/recalcitrance and higher
      on facilitating anxiety spent more time sedentary in adulthood. Girls with a
      superior standing high jump performance, and a lower score on social desirability
      spent more time sedentary in adulthood. In contrast with sedentary behaviour,
      physical activity at age 42 year could not be predicted by physical
      characteristics or personality in adolescence. CONCLUSIONS: Sedentary behaviour
      in adulthood was partly explained by physical characteristics and/or personality
      in adolescence. Thus, our results suggest that it may be possible to identify
      people who are at risk of becoming sedentary at a rather young age.

PMID- 21961796
TI  - Cost-effectiveness of insulin detemir: a systematic review.
AB  - The prevalence of diabetes and cost of associated treatment are steadily
      increasing, as is the resulting burden on healthcare systems worldwide. Current
      treatment recommendations for Type 1 and Type 2 diabetes advise a prominent role
      for basal insulin. We examined the published health-economic literature
      pertaining to the basal insulin analog insulin detemir (IDet) to determine
      whether IDet is a cost-saving and/or cost-effective treatment for suboptimally
      controlled Type 1 or Type 2 diabetes. A total of 15 modeling studies were
      assessed, most of which found IDet to be cost effective compared with neutral
      protamine Hagedorn and as cost effective as insulin glargine. Those that did not
      find IDet to be cost effective set the disutility of hypoglycemic events to
      almost zero or assumed a higher dose of IDet with no difference in treatment
      effect, ignoring the clinical benefits and cost savings associated with IDet in
      studies demonstrating comparable or superior glycemic control with less
      hypoglycemia versus other basal insulins. The evidence suggests that IDet is cost
      effective versus neutral protamine Hagedorn and at least as cost effective as
      insulin glargine in the treatment of patients with suboptimally controlled Type 1
      and Type 2 diabetes.

PMID- 21961797
TI  - Charge and size selective molecular transport by amphiphilic organic nanotubes.
AB  - Amphiphilic constructs with accessible, nanometer-size cavities can enable
      selective encapsulation, separation, and purification of nanomaterials and
      biomacromolecules on a similar length scale. We have developed a new method for
      the fabrication of amphiphilic organic nanotubes from multicomponent bottlebrush
      copolymers with triblock terpolymer side chains. The obtained nanotubes were
      demonstrated to be very effective and highly selective carriers for positively
      charged molecules and nanometer-size macromolecules by means of liquid-liquid
      extractions. Unprecedented discrimination between dendrimers with about 2 nm size
      differential was achieved.

PMID- 21961798
TI  - Stakeholders understanding of the concept of benefit sharing in health research
      in Kenya: a qualitative study.
AB  - BACKGROUND: The concept of benefit sharing to enhance the social value of global
      health research in resource poor settings is now a key strategy for addressing
      moral issues of relevance to individuals, communities and host countries in
      resource poor settings when they participate in international collaborative
      health research.The influence of benefit sharing framework on the conduct of
      collaborative health research is for instance evidenced by the number of
      publications and research ethics guidelines that require prior engagement between
      stakeholders to determine the social value of research to the host communities.
      While such efforts as the production of international guidance on how to promote
      the social value of research through such strategies as benefit sharing have been
      made, the extent to which these ideas and guidelines have been absorbed by those
      engaged in global health research especially in resource poor settings remains
      unclear. We examine this awareness among stakeholders involved in health related
      research in Kenya. METHODS: We conducted in-depth interviews with key informants
      drawn from within the broader health research system in Kenya including
      researchers from the mainstream health research institutions, networks and
      universities, teaching hospitals, policy makers, institutional review boards,
      civil society organisations and community representative groups. RESULTS: Our
      study suggests that although people have a sense of justice and the moral aspects
      of research, this was not articulated in terms used in the literature and the
      guidelines on the ethics of global health research. CONCLUSION: This study
      demonstrates that while in theory several efforts can be made to address the
      moral issues of concern to research participants and their communities in
      resource poor settings, quick fixes such as benefit sharing are not going to be
      straightforward. We suggest a need to pay closer attention to the processes
      through which ethical principles are enacted in practice and distil lessons on
      how best to involve individuals and communities in promoting ethical conduct of
      global health research in resource poor settings.

PMID- 21961799
TI  - Gyration- and inertia-tensor-based collective coordinates for metadynamics.
      Application on the conformational behavior of polyalanine peptides and Trp-cage
      folding.
AB  - Effective simulations of proteins, their complexes, and other amino-acid polymers
      such as peptides or peptoids are critically dependent on the performance of the
      simulation methods and their ability to map the conformational space of the
      molecule in question. The most important step in this process is the choice of
      the coordinates in which the conformational sampling will be executed and their
      uniqueness regarding the capability to unambiguously determine the energy minimum
      on the free-energy hypersurface. In the presented study, we show that
      metadynamics and chosen collective coordinates-the principal moments of the
      tensors of gyration and inertia, the principal radii of gyration around the
      principal axes, asphericity, acylindricity, and anisotropy-can be used as a
      powerful combination to map the conformational space of peptides and proteins. We
      show that the combination of these coordinates with metadynamics produces a
      powerful tool for the study of biologically relevant molecules.

PMID- 21961800
TI  - Effects of prenatal exposure to cigarette smoke on use of xanthine and pneumogram
      evaluation at discharge in premature infants.
AB  - OBJECTIVE: Prenatal exposure to cigarette smoke is associated with an increased
      risk of sudden infant death syndrome and possible rate increase of obstructive
      apnea in full-term infants but unknown in premature infants. Therefore, the
      objective was to study the effect of prenatal exposure to cigarette smoke on the
      use of methylxanthines and discharge pneumograms in premature infants. METHODS:
      Preterm infants [gestational age (GA) <=34 weeks] born between January 1997 and
      September 2007 were studied. A four-channel pneumogram was performed at
      discharge. Relevant clinical data were collected from the infant's records.
      Infants with prenatal exposure to cigarette smoke were compared with infants not
      exposed (controls). RESULTS: A total of 1656 infants were studied: 263 infants
      {birth weight (BW) (mean +/- SD) 1682 +/- 566 g, GA 31.0 +/- 2.8 weeks} exposed
      to prenatal cigarette smoke and 1393 infants (BW 1638 +/- 575 g, GA 31.1 +/- 2.7
      weeks) not exposed. Baseline patient characteristics were similar between the two
      groups. When comparing the smoking versus control groups, there was no
      significant difference in the infants for the following: xanthine therapy and
      abnormal pneumograms; presence of central, obstructed or mixed apnea and home
      discharge on monitors, oxygen and xanthines. CONCLUSIONS: Prenatal exposure to
      cigarette smoke was not associated with increased use of xanthines or abnormal
      pneumogram in premature infants.

PMID- 21961801
TI  - The effectiveness of problem solving therapy in deprived South African
      communities: results from a pilot study.
AB  - BACKGROUND: The majority of South Africans with a DSM-IV diagnosis receive no
      treatment for their mental health problems. There is a move to simplify treatment
      for common mental disorders (CMDs) in order to ease access. Brief problem solving
      therapy (PST) might fill the treatment gap for CMD's in deprived communities in
      South Africa. This pilot study evaluates the feasibility, acceptability and
      effectiveness of this PST program for CMD's in deprived communities around Cape
      Town. METHODS: A Dutch problem solving program was adapted and translated into
      English, Xhosa and Afrikaans and thereafter implemented in townships around Cape
      Town. An initial attempt to recruit participants for online PST proved difficult,
      and so the program was adapted to a booklet format. Volunteers experiencing
      psychological distress were invited to participate in the either individually or
      group delivered 5-week during self-help program. To evaluate the effectiveness,
      psychological distress was administered through self-report questionnaires. After
      completion of the intervention participants also rated the program on various
      acceptability aspects. RESULTS: Of 103 participants, 73 completed 5 weeks of
      brief PST in a booklet/workshop format. There were significantly more dropouts in
      those who used the booklet individually than in the group. Psychological distress
      measured on the K-10 and SRQ fell significantly and the program was evaluated
      positively. CONCLUSIONS: The results suggest that brief problem solving in a
      booklet/workshop format may be an effective, feasible and acceptable short-term
      treatment for people with CMD's in deprived communities. In this setting, group
      delivery of PST had lower drop-out rates than individual delivery, and was more
      feasible and acceptable. Randomized controlled trials are needed to evaluate the
      effect of brief self-help PST more rigorously.

PMID- 21961803
TI  - Pricing risk and ambiguity: the effect of perspective taking.
AB  - In the valuation of uncertain prospects, a difference is often observed between
      selling and buying perspectives. This paper distinguishes between risk (known
      probabilities) and ambiguity (unknown probabilities) in decisions under
      uncertainty and shows that the valuation disparity increases under ambiguity
      compared to risk. It is found that both the comparative versus noncomparative
      evaluation of risky and ambiguous prospects and the uniqueness of the valuation
      perspective (either seller or buyer) moderate this increase in the disparity
      under ambiguity. The finding is consistent with recent theoretical accounts of
      pricing under uncertainty. We discuss implications for market behaviour and for
      the ambiguity paradigm as a research tool.

PMID- 21961802
TI  - Routine processing procedures for isolating filamentous fungi from respiratory
      sputum samples may underestimate fungal prevalence.
AB  - Colonization of the airways by filamentous fungi can occur in asthma, chronic
      obstructive pulmonary disease (COPD) and cystic fibrosis. A recent study found
      IgE sensitization to Aspergillus fumigatus to be associated with reduced lung
      function. Significantly higher rates of A. fumigatus were detected in sputum from
      asthmatics sensitized to this fungus compared to non-sensitized asthmatics. The
      rate of positive cultures was far higher than equivalent historical samples
      analysed by the local clinical laboratory following protocols recommended by the
      UK Health Protection Agency (HPA). This study compares the HPA procedure with our
      sputum processing method, whereby sputum plugs are separated from saliva and
      aliquots of approximately 150 mg are inoculated directly onto potato dextrose
      agar. A total of 55 sputum samples from 41 patients with COPD were analyzed,
      comparing fungal recovery of five dilutions of sputa on two media. Isolation of
      A. fumigatus in culture was significantly higher using the research approach
      compared to the HPA standard method for mycological investigations (P < 0.001).
      There was also a significant difference in the recovery rate of A. fumigatus (P <
      0.05) between media. This highlights the need for a standardized approach to
      fungal detection which is more sensitive than the method recommended by the HPA.

PMID- 21961804
TI  - Vibrational coherence spectroscopy of the heme domain in the CO-sensing
      transcriptional activator CooA.
AB  - Femtosecond vibrational coherence spectroscopy was used to investigate the low
      frequency vibrational dynamics of the heme in the carbon monoxide oxidation
      activator protein (CooA) from the thermophilic anaerobic bacterium
      Carboxydothermus hydrogenoformans (Ch-CooA). Low frequency vibrational modes are
      important because they are excited by the ambient thermal bath (k(B)T = 200 cm(
      1)) and participate in thermally activated barrier crossing events. However, such
      modes are nearly impossible to detect in the aqueous phase using traditional
      spectroscopic methods. Here, we present the low frequency coherence spectra of
      the ferric, ferrous, and CO-bound forms of Ch-CooA in order to compare the
      protein-induced heme distortions in its active and inactive states. Distortions
      take place predominantly along the coordinates of low-frequency modes because of
      their weak force constants, and such distortions are reflected in the intensity
      of the vibrational coherence signals. A strong mode near ~90 cm(-1) in the
      ferrous form of Ch-CooA is suggested to contain a large component of heme
      ruffling, consistent with the imidazole-bound ferrous heme crystal structure,
      which shows a significant protein-induced heme distortion along this coordinate.
      A mode observed at ~228 cm(-1) in the six-coordinate ferrous state is proposed to
      be the nu(Fe-His) stretching vibration. The observation of the Fe-His mode
      indicates that photolysis of the N-terminal alpha-amino axial ligand takes place.
      This is followed by a rapid (~8.5 ps) transient absorption recovery, analogous to
      methionine rebinding in photolyzed ferrous cytochrome c. We have also studied CO
      photolysis in CooA, which revealed very strong photoproduct state coherent
      oscillations. The observation of heme-CO photoproduct oscillations is unusual
      because most other heme systems have CO rebinding kinetics that are too slow to
      make the measurement possible. The low frequency coherence spectrum of the CO
      bound form of Ch-CooA shows a strong vibration at ~230 cm(-1) that is broadened
      and up-shifted compared to the nu(Fe-His) of Rr-CooA (216 cm(-1)). We propose
      that the stronger Fe-His bond is related to the enhanced thermal stability of Ch
      CooA and that there is a smaller (time dependent) tilt of the histidine ring with
      respect to the heme plane in Ch-CooA. The appearance of strong modes at ~48 cm(
      1) in both the ferrous and CO-bound forms of Ch-CooA is consistent with coupling
      of the heme doming distortion to the photolysis reaction in both samples. Upon CO
      binding and protein activation, a heme mode near 112 +/- 5 cm(-1) disappears,
      probably indicating a decreased heme saddling distortion. This reflects changes
      in the heme environment and geometry that must be associated with the
      conformational transition activating the DNA-binding domain. Protein-specific DNA
      binding to the CO-bound form of Ch-CooA was also investigated, and although the
      CO rebinding kinetics are significantly perturbed, there are negligible changes
      in the low-frequency vibrational spectrum of the heme.

PMID- 21961807
TI  - The management of fibroids based on immunohistochemical studies of their
      pseudocapsules.
AB  - BACKGROUND: We examined the presence of collagen IV and laminin in the
      pseudocapsule of uterine myomata to clarify different ultra-structural
      characteristics and their possible role in the management of this condition.
      METHODS: Twenty non-pregnant patients underwent laparoscopic intracapsular
      myomectomies. Samples of the removed fibroids pseudocapsules were analyzed by
      immunochemical staining for collagen IV, immunohistochemical location of the
      vascular membrane-bound laminin and quantitative analysis of their images.
      RESULTS: In the blood vessels of the pseudocapsules, a reduction in laminin and
      increase in collagen IV with increasing diameter of fibroids was noted. These
      proteins are related to loss of the basal membrane and to ageing of the tissue.
      The increase of collagen IV is linked to the increase of amorphous substance,
      including glycosaminoglycans and glycoproteins. CONCLUSION: Based on
      immunohistochemical findings, the authors propose to remove fibroids in women
      seeking pregnancy whilst respecting the pseudocapsule by neurofibre sparing in
      the incision site. This is essential for optimal muscular healing and myometrial
      function in future pregnancies, and also when fibroids remain under 6 cm
      diameter, especially in young women wishing pregnancies. Fibroid removal should
      be performed before the myoma reaches a size causing compression of the
      surrounding tissues, which results in the loss of regenerative potential.

PMID- 21961805
TI  - Radiation induced temporal lobe necrosis in patients with nasopharyngeal
      carcinoma: a review of new avenues in its management.
AB  - Temporal lobe necrosis (TLN) is the most debilitating late-stage complication
      after radiation therapy in patients with nasopharyngeal cancer (NPC). The
      bilateral temporal lobes are inevitably encompassed in the radiation field and
      are thus prone to radiation induced necrosis. The wide use of 3D conformal and
      intensity-modulated radiation therapy (IMRT) in the treatment of NPC has led to a
      dwindling incidence of TLN. Yet, it still holds great significance due to its
      incapacitating feature and the difficulties faced clinically and radiologically
      in distinguishing it from a malignancy. In this review, we highlight the
      evolution of different imaging modalities and therapeutic options. FDG PET, SPECT
      and Magnetic Spectroscopy are among the latest imaging tools that have been
      considered. In terms of treatment, Bevacizumab remains the latest promising
      breakthrough due to its ability to reverse the pathogenesis unlike conventional
      treatment options including large doses of steroids, anticoagulants, vitamins,
      hyperbaric oxygen and surgery.

PMID- 21961808
TI  - First-year purchases of disease-modifying drugs of incident patients with chronic
      juvenile arthritis in Finland.
AB  - OBJECTIVES: To establish a nationwide overview on drug treatment of juvenile
      idiopathic arthritis (JIA), which is the most frequent form of chronic arthritis
      (JA) in children and adolescents. The emphasis is on the first 12 months after
      diagnosis, and any changes in medication practices during the early years of the
      present millennium are registered. METHODS: The Social Insurance Institution
      (SII) in Finland keeps a national register on individuals granted with a special
      reimbursement for medication of defined chronic diseases. From that register, we
      identified by the ICD-code of M08 all JA patients aged 16 years or under with an
      index day from 2000 through 2007. The prescription register of the SII showed the
      medication purchased for the patients. The register does not cover infused
      medications given in hospitals. We evaluated the first disease year's medication
      and the treatment strategy of the very first three months. RESULTS: Within our
      study period 2000-2007, the proportion of patients using methotrexate during the
      first year of treatment increased from 54 to 72% (p<0.001). The combination of
      two or more DMARDs became more popular (increased from 16 to 21%) as the initial
      treatment strategy. These changes parallel a decrease in per oral
      glucocorticoids. The proportion of JA patients receiving TNFalpha-blockers during
      the first year after diagnose reached the level of about 5% during the years 2004
      to 007. CONCLUSIONS: The drug treatment of patients with recent onset JA has
      become more intensive during the course of the new millennium in Finland, a fact
      expected to improve the disease outcome.

PMID- 21961809
TI  - Measurement of tear glucose levels with amperometric glucose biosensor/capillary
      tube configuration.
AB  - An amperometric needle-type electrochemical glucose sensor intended for tear
      glucose measurements is described and employed in conjunction with a 0.84 mm i.d.
      capillary tube to collect microliter volumes of tear fluid. The sensor is based
      on immobilizing glucose oxidase on a 0.25 mm o.d. platinum/iridium (Pt/Ir) wire
      and anodically detecting the liberated hydrogen peroxide from the enzymatic
      reaction. Inner layers of Nafion and an electropolymerized film of 1,3
      diaminobenzene/resorcinol greatly enhance the selectivity for glucose over
      potential interferences in tear fluid, including ascorbic acid and uric acid.
      Further, the new sensor is optimized to achieve very low detection limits of 1.5
      +/- 0.4 MUM of glucose (S/N = 3) that is required to monitor glucose levels in
      tear fluid with a glucose sensitivity of 0.032 +/- 0.02 nA/MUM (n = 6). Only 4-5
      MUL of tear fluid in the capillary tube is required when the needle sensor is
      inserted into the capillary. The glucose sensor was employed to measure tear
      glucose levels in anesthetized rabbits over an 8 h period while also measuring
      the blood glucose values. A strong correlation between tear and blood glucose
      levels was found, suggesting that measurement of tear glucose is a potential
      noninvasive substitute for blood glucose measurements, and the new sensor
      configuration could aid in conducting further research in this direction.

PMID- 21961810
TI  - Extremely discrepant mutation spectrum of SLC26A4 between Chinese patients with
      isolated Mondini deformity and enlarged vestibular aqueduct.
AB  - BACKGROUND: Mutations in SLC26A4 cause Pendred syndrome (hearing loss with
      goiter) or DFNB4 (non-syndromic hearing loss with inner ear malformation, such as
      enlarged vestibular aqueduct or Mondini deformity). The relationship between
      mutations in SLC26A4 and Mondini deformity without enlarged vestibular aqueduct
      has not been studied in any Chinese deaf population. The purpose of this study
      was to assess whether mutations in the SLC26A4 gene cause Mondini deformity
      without an enlarged vestibular aqueduct (isolated Mondini deformity) in a Chinese
      population. METHODS: In total, 144 patients with sensorineural hearing loss were
      included and subjected to high-resolution temporal bone CT. Among them, 28
      patients with isolated Mondini dysplasia (MD group), 50 patients with enlarged
      vestibular aqueduct with Mondini dysplasia (EVA with MD group), 50 patients with
      enlarged vestibular aqueduct without Mondini dysplasia (EVA group), and 16
      patients with other types of inner ear malformations (IEM group) were identified.
      The coding exons of SLC26A4 were analyzed in all subjects. RESULTS: DNA sequence
      analysis of SLC26A4 was performed in all 144 patients. In the different groups,
      the detection rate of the SLC26A4 mutation differed. In the isolated MD group,
      only one single allelic mutation in SLC26A4 was found in one patient (1/28,
      3.6%). In the EVA with MD group, biallelic and monoallelic SLC26A4 mutations were
      identified in 46 patients (46/50, 92.0%) and three patients (3/50, 6.0%),
      respectively. Also, in the EVA group, biallelic and monoallelic SLC26A4 mutations
      were identified in 46 patients (46/50, 92.0%) and three patients (3/50, 6.0%),
      respectively. These percentages were identical to those in the EVA plus MD group.
      Only two patients carried monoallelic mutations of the SLC26A4 gene in the IEM
      group (2/16, 12.5%). There were significant differences in the frequency of
      SLC26A4 mutation among the groups (P<0.001). The detection rate of SLC26A4
      mutation in the isolated MD group was significantly lower than in the EVA group
      (with or without MD; P<0.001), and there was no significant difference in the
      detection rate of SLC26A4 between the MD group and IEM group (P>0.5). CONCLUSION:
      Although mutations in the SLC26A4 gene were frequently found in Chinese EVA
      patients with and without MD, there was no evidence to show a relationship
      between isolated MD and the SLC26A4 gene in the Chinese population examined.
      Hearing impairment in patients with isolated MD may be caused by factors other
      than mutations in the SLC26A4 gene.

PMID- 21961812
TI  - Piezotronic effect on the output voltage of P3HT/ZnO micro/nanowire
      heterojunction solar cells.
AB  - We report the first observation of piezotronic effect on the output voltage of a
      flexible heterojunction solar cell. The solar cell was fabricated by contacting
      poly(3-hexylthiophene) (P3HT) with one end of a ZnO micro/nanowire to form a p-n
      heterojunction on a flexible polystyrene (PS) substrate. The open-circuit voltage
      V(oc) of the solar cell was characterized by tuning the strain-induced
      polarization charges at the interface between ZnO and P3HT. The experimental data
      were understood based on the modification of the band structure at the p-n
      junction by the piezopotential, which is referred as a result of the piezotronic
      effect. This study not only provides an in-depth understanding about the effect
      but also is useful for maximizing the output of a solar cell using wurtzite
      structured materials.

PMID- 21961811
TI  - Two cases of monomicrobial intraabdominal abscesses due to KPC--3 Klebsiella
      pneumoniae ST258 clone.
AB  - BACKGROUND: Knowledge of the etiology of pyogenic liver and pancreatic abscesses
      is an important factor in determining the success of combined surgical and
      antibiotic treatment. Literature shows geographical variations in the prevalence
      and distribution of causative organisms, and the spread of Klebsiella pneumoniae
      carbapenemase-producing bacteria is an emerging cause of abdominal infections.
      CASE PRESENTATION: We herein describe two cases of intra-abdominal abscesses due
      to monomicrobial infection by Klebsiella pneumoniae Sequence Type 258 producing
      K. pneumoniae carbapenemase 3 (KPC-Kp). In case 1, a 50-year-old HIV-negative
      Italian woman with chronic pancreatitis showed infection of a pancreatic
      pseudocystic lesion caused by KPC-Kp. In case 2, a 64-year-old HIV-negative
      Italian woman with pancreatic neoplasm and liver metastases developed a liver
      abscess due to KPC after surgery. Both women were admitted to our hospital but to
      different surgical units. The clonal relationship between the two isolates was
      investigated by pulsed-field gel electrophoresis (PFGE). In case 2, the patient
      was already colonized at admission and inter-hospital transmission of the
      pathogen was presumed. A long-term combination regimen of colistin with
      tigecycline and percutaneous drainage resulted in full recovery and clearance of
      the multidrug-resistant (MDR) pathogen. CONCLUSIONS: Timely microbiological
      diagnosis, the combined use of new and old antibiotics and radiological
      intervention appeared to be valuable in managing these serious conditions. The
      emergence and dissemination of MDR organisms is posing an increasing challenge
      for physicians to develop new therapeutic strategies and control and prevention
      frameworks.

PMID- 21961813
TI  - Improved efficacy by using the pTnT-rhtTG plasmid for the detection of celiac
      disease specific tissue transglutaminase autoantibodies in radioligand binding
      assays.
AB  - BACKGROUND: Tissue transglutaminase (tTG) autoantibodies are serological markers
      for celiac disease. The aim was to study the efficacy of the pTnT-rhtTG plasmid
      and subsequent diagnostic accuracy of tTG autoantibodies for childhood celiac
      disease using radioligand binding assays. METHODS: Coupled in vitro transcription
      and translation of tTG were performed by pTnT-rhtTG as well as by the pGEMt Easy
      rhtTG vectors using the TNT SP6 Coupled Reticulocyte Lysate System in the
      presence of [35S] methionine. Sera from 190 celiac disease children and 74
      controls were measured for tTG autoantibodies in two separate radioligand binding
      assays using anti-human IgA agarose and protein A sepharose beads for the
      detection of IgA-tTG and IgG-tTG, respectively. RESULTS: Median incorporation of
      [35S] methionine into the pTnT-rhtTG was 26% compared to 16% for the pGEMt Easy
      rhtTG plasmid (p = 0.0016). Using pTnT-rhtTG (as compared to pGEMt Easy-rhtTG),
      sensitivities were IgA-tTG = 96.3% (95.7%) and IgG-tTG = 95.8% (97.3%) and
      specificities were IgA-tTG = 91.9% (90.5%) and IgG-tTG = 94.6% (98.4%). According
      to receiver operator characteristics for the pTnT (pGEMt Easy) assays, area under
      the curves were IgA-tTG = 98.4% (98.4%) and IgG-tTG = 97.7% (97.2%),
      respectively. CONCLUSION: The pTnT-rhtTG plasmid increased the efficacy of tTG
      antigen usage without reducing the diagnostic accuracy of IgA-tTG and IgG-tTG for
      childhood celiac disease. The pTnT-rhtTG plasmid is therefore recommended over
      the pGEMt Easy-rhtTG for the assessment of IgA-tTG and IgG-tTG using radioligand
      binding assays.

PMID- 21961814
TI  - Evaluation of the relationship between capillary and venous plasma glucose
      concentrations obtained by the HemoCue Glucose 201+ system during an oral glucose
      tolerance test.
AB  - In 55 women with previous gestational diabetes mellitus, simultaneous capillary
      and venous plasma glucose concentrations were measured at 0, 30 and 120 min
      during a 75 g oral glucose tolerance test (OGTT). The aims of the study were to
      examine the relationship between capillary and venous glucose measurements, and
      to establish equations for the conversion of capillary and venous glucose
      concentrations using the HemoCue Glucose 201+ system. Additionally, the
      correlation between the capillary and venous glucose concentrations with the
      diagnostic cut-off limits proposed by the World Health Organization (WHO) in 1999
      was evaluated. Capillary glucose concentrations were consistently higher than
      venous glucose concentrations at all time points of the OGTT (p < 0.001), and the
      correlations between the measurements were statistically highly significant (p <
      0.001). The differences between the samples were greatest in the non-fasting
      state as revealed by the 95% prediction intervals (mmol/L) in Bland-Altman plots;
      +/- 0.54 at 0 min, +/- 2.01 at 30 min, and +/- 1.35 at 120 min. Equivalence
      values for capillary plasma glucose concentrations derived from this study tended
      to be higher than those proposed by the WHO as diagnostic cut-off limits.
      Stratifying subjects by glucose tolerance status according to the WHO criteria
      revealed disagreements related to glucose values close to the diagnostic cut-off
      points. The study findings highlight the uncertainty associated with derived
      equivalence values. However, capillary plasma glucose measurements could be
      suitable for diagnostic purposes in epidemiological studies and when translating
      results on a group basis.

PMID- 21961818
TI  - The state of hormonal contraception today: overview of unintended pregnancy.
AB  - Each year in the United States about 1 in 20 women experiences an unintended
      pregnancy. Understanding the impact of consistent, appropriate, and effective
      contraception on this major health care concern is key to overcoming this
      societal and economic burden. In addition to available family-planning services,
      women need ongoing support in choosing and using methods based on her overall
      life situation, as well as strategies to address the logistic and cost barriers
      to effective birth control.

PMID- 21961819
TI  - The state of hormonal contraception today: benefits and risks of hormonal
      contraceptives: progestin-only contraceptives.
AB  - The progestin component of hormonal contraceptives accounts for most of their
      contraceptive effects. Several dosage forms of progestin-only contraceptives have
      been developed, including pills, injectables, implants, and intrauterine devices.
      Emergency contraceptives may also contain progestin only and are indicated for
      prevention of pregnancy following unprotected intercourse or contraceptive
      failure. Each form has benefits, some specific to the form. An understanding of
      benefits and risks allows clinicians a wider choice when recommending effective
      hormonal contraception.

PMID- 21961820
TI  - The state of hormonal contraception today: enhancing clinician/patient
      communications.
AB  - Women's health nurses and nurse practitioners have a unique opportunity to
      provide high-quality primary and preventive care and play a critical role in
      coordinating and delivering effective contraceptive methods. The strategies and
      techniques that they routinely employ during counseling and education can help
      improve women's adoption and appropriate use of contraceptive methods.

PMID- 21961821
TI  - The future of contraception: innovations in contraceptive agents: tomorrow's
      hormonal contraceptive agents and their clinical implications.
AB  - Currently available contraceptive methods have not eliminated the burden of
      unintended pregnancy. Future progress will require technological advancements,
      leading to the development of novel and highly effective birth control strategies
      that will be acceptable to the general population. Included are highlights of
      some of the ongoing research, demonstrating the development of methods with the
      potential to be highly effective, widely accepted, easy to use, and more cost
      effective, with fewer side effects, than currently available options.

PMID- 21961822
TI  - Family planning and the future.
AB  - The adoption of Title X in 1971 provided for public funding for family planning
      in the United States but funding from this program has not kept pace with demand
      for contraceptives. In 1997, The California Department of Public Health
      established the Family Planning, Access, Care, and Treatment (PACT) Program, a
      public-private partnership to meet the needs of Californians, including about a
      half-million adolescents, who did not have access to contraceptive services. The
      program has saved the state billions of dollars in maternity and abortion costs,
      dramatically reduced teen pregnancy rates, and serves as a good example for other
      states.

PMID- 21961823
TI  - The future of contraception: the future leaders of family planning.
AB  - The University of California, San Francisco, initiated a Fellowship in Family
      Planning in 1991, and since then 23 academic teaching hospitals across the
      country have adopted the 2 year program model for training obstetrician
      gynecologist physicians in a subspecialty focused on contraception and abortion.
      The program follows a curriculum that includes clinical practice, research, and
      international work. This review includes information about the Fellowship in
      Family Planning as well as research opportunities available from academia,
      independent foundations, and government related sources.

PMID- 21961824
TI  - The state of hormonal contraception today: established and emerging
      noncontraceptive health benefits.
AB  - In the 50 years since the advent of combined oral contraceptives the amount of
      estrogen in oral contraceptives dropped from over 100 mcg to less than 30 mcg.
      Many noncontraceptive health benefits have emerged that decrease mortality and
      improve quality of life. Some of the immediate benefits include improvement of
      menorrhagia and dysmenorrhea, reduction in premenstrual dysphoric disorder
      symptoms, and decreased acne. As an effective birth control method oral
      contraceptives also decrease pregnancy-related deaths by preventing pregnancy.
      After the reproductive years, previous use of oral contraceptives continues to be
      beneficial, reducing the risk of death from ovarian and endometrial cancer. All
      these benefits have held up over time whereas cardiovascular risks have lessened
      because of the decrease in oral contraceptive pill dosage. Decreased ovarian cyst
      formation is an example of benefit with higher-dose oral contraceptive
      formulations that no longer holds true with low-dose pills.

PMID- 21961825
TI  - The state of hormonal contraception today: benefits and risks of hormonal
      contraceptives: combined estrogen and progestin contraceptives.
AB  - Discussion of effective birth control methods can be a challenging process for
      clinicians because the adoption and consistent use of contraception may be
      influenced by patients' fears, myths, and misperceptions. Over the years, new
      progestins have been included in combination contraceptives or are used alone to
      provide effective contraception as well as to decrease androgenic side effects
      and ameliorate the symptoms of premenstrual dysphoric disorder. Alternative
      delivery systems and regimens have also been introduced to improve tolerability
      and continuance and convenience of use. This is a review of estrogen and
      progestin combinations and their effects.

PMID- 21961826
TI  - Spatially resolved sources of dark current from TiO2 nanoparticle electrodes.
AB  - The properties of TiO(2) and polyphenyl oxide (PPO) blocking layers were compared
      using a highly positive redox shuttle in dye-sensitized solar cells. The dark
      current versus applied potential curve was found to be composed of two separate
      current features. Cyclic voltammetric and impedance measurements were performed
      to identify the source of the two features. The first feature results from
      electron transfer from the TiO(2) blocking layer and the first layer of the
      TiO(2) nanoparticle film contacting the substrate. The second onset of dark
      current results from the transport resistance in the nanoparticle film
      decreasing, thus allowing electron transfer to occur throughout the film. It is
      further demonstrated that PPO prevents back electron transfer from the conductive
      substrate to the redox shuttle across the entire potential range studied;
      however, the TiO(2) blocking layer is active and participates in electron
      transfer at rates similar to those of the TiO(2) nanoparticle film.

PMID- 21961827
TI  - Evaluating complex interventions and health technologies using normalization
      process theory: development of a simplified approach and web-enabled toolkit.
AB  - BACKGROUND: Normalization Process Theory (NPT) can be used to explain
      implementation processes in health care relating to new technologies and complex
      interventions. This paper describes the processes by which we developed a
      simplified version of NPT for use by clinicians, managers, and policy makers, and
      which could be embedded in a web-enabled toolkit and on-line users manual.
      METHODS: Between 2006 and 2010 we undertook four tasks. (i) We presented NPT to
      potential and actual users in multiple workshops, seminars, and presentations.
      (ii) Using what we discovered from these meetings, we decided to create a
      simplified set of statements and explanations expressing core constructs of the
      theory (iii) We circulated these statements to a criterion sample of 60
      researchers, clinicians and others, using SurveyMonkey to collect qualitative
      textual data about their criticisms of the statements. (iv) We then reconstructed
      the statements and explanations to meet users' criticisms, embedded them in a web
      enabled toolkit, and beta tested this 'in the wild'. RESULTS: On-line data
      collection was effective: over a four week period 50/60 participants responded
      using SurveyMonkey (40/60) or direct phone and email contact (10/60). An
      additional nine responses were received from people who had been sent the
      SurveyMonkey form by other respondents. Beta testing of the web enabled toolkit
      produced 13 responses, from 327 visits to http://www.normalizationprocess.org.
      Qualitative analysis of both sets of responses showed a high level of support for
      the statements but also showed that some statements poorly expressed their
      underlying constructs or overlapped with others. These were rewritten to take
      account of users' criticisms and then embedded in a web-enabled toolkit. As a
      result we were able translate the core constructs into a simplified set of
      statements that could be utilized by non-experts. CONCLUSION: Normalization
      Process Theory has been developed through transparent procedures at each stage of
      its life. The theory has been shown to be sufficiently robust to merit formal
      testing. This project has provided a user friendly version of NPT that can be
      embedded in a web-enabled toolkit and used as a heuristic device to think through
      implementation and integration problems.

PMID- 21961828
TI  - Dynamics of carbene cycloadditions.
AB  - Quasiclassical trajectory calculations using quantum mechanical energies and
      forces generated by the Venus and Gaussian programs provide for the first time a
      detailed dynamical picture of singlet carbene, CCl(2) and CF(2), cycloadditions
      to alkenes on the B3LYP/6-31G* surface. For CF(2), B3LYP/6-31G* with exact
      exchange reduced to 12% HF was also employed to better mimic the high accuracy
      surface. The range of geometries sampled in reactive trajectories and the timing
      of bond formation were explored. All trajectories follow the nonlinear approach
      proposed by Moore and Hoffmann. The reaction of CCl(2) with ethylene is a
      dynamically concerted reaction, with an average time gap between formation of the
      two bonds of 50 fs. The reaction of CF(2) with ethylene is dynamically complex
      with biexponential decay of the diradical species formed from the first bond
      formation. A general quantitative dynamical classification of cycloaddition
      mechanisms is proposed, based on the timing of bond formation.

PMID- 21961829
TI  - Service user and carer experiences of seeking help for a first episode of
      psychosis: a UK qualitative study.
AB  - BACKGROUND: Long duration of untreated psychosis (DUP) is associated with poor
      outcomes and low quality of life at first contact with mental health services.
      However, long DUP is common. In order to inform initiatives to reduce DUP, we
      investigated service users' and carers' experiences of the onset of psychosis and
      help-seeking in two multicultural, inner London boroughs and the roles of
      participants' social networks in their pathways to care. METHOD: In-depth
      interviews were conducted with service users and carers from an early
      intervention service in North London, purposively sampled to achieve diversity in
      sociodemographic characteristics and DUP and to include service users in contact
      with community organisations during illness onset. Interviews covered
      respondents' understanding of and reaction to the onset of psychosis, their help
      seeking attempts and the reactions of social networks and health services.
      Thematic analysis of interview transcripts was conducted. RESULTS: Multiple
      barriers to prompt treatment included not attributing problems to psychosis,
      worries about the stigma of mental illness and service contact, not knowing where
      to get help and unhelpful service responses. Help was often not sought until
      crisis point, despite considerable prior distress. The person experiencing
      symptoms was often the last to recognise them as mental illness. In an urban UK
      setting, where involved, workers in non-health community organisations were
      frequently willing to assist help-seeking but often lacked skills, time or
      knowledge to do so. CONCLUSION: Even modest periods of untreated psychosis cause
      distress and disruption to individuals and their families. Early intervention
      services should prioritise early detection. Initiatives aimed at reducing DUP may
      succeed not by promoting swift service response alone, but also by targeting
      delays in initial help-seeking. Our study suggests that strategies for doing this
      may include addressing the stigma associated with psychosis and community
      education regarding symptoms and services, targeting not only young people
      developing illness but also a range of people in their networks, including staff
      in educational and community organisations. Initiatives to enhance the effective
      involvement of staff in community organisations working with young people in
      promoting help-seeking merit research.

PMID- 21961830
TI  - Commissioning and early experience with a new-generation low-energy linear
      accelerator with advanced delivery and imaging functionalities.
AB  - BACKGROUND: A new-generation low-energy linear accelerator (UNIQUE) was
      introduced in the clinical arena during 2009 by Varian Medical Systems. The
      world's first UNIQUE was installed at Oncology Institute of Southern Switzerland
      and put into clinical operation in June 2010. The aim of the present contribution
      was to report experience about its commissioning and first year results from
      clinical operation. METHODS: Commissioning data, beam characteristics and the
      modeling into the treatment planning system were summarized. Imaging system of
      UNIQUE included a 2D-2D matching capability and tests were performed to identify
      system repositioning capability. Finally, since the system is capable of
      delivering volumetric modulated arc therapy with RapidArc, a summary of the tests
      performed for such modality to assess its performance in preclinical settings and
      during clinical usage was included. RESULTS: Isocenter virtual diameter was
      measured as less than 0.2 mm. Observed accuracy of isocenter determination and
      repositioning for 2D-2D matching procedures in image guidance was <1.2 mm.
      Concerning reproducibility and stability over a period of 1 year, deviations from
      reference were found <0.3 +/- 0.2% for linac output, <0.1% for homogeneity,
      similarly to symmetry. Rotational accuracy of the entire gantry-portal imager
      system showed a maximum deviation from nominal 0.0 of <1.2 mm. Pre treatment
      quality assurance of RapidArc plans resulted with a Gamma Agreement Index
      (fraction of points passing the gamma criteria) of 97.0 +/- 1.6% on the first 182
      arcs verified. CONCLUSIONS: The results of the commissioning tests and of the
      first period of clinical operation, resulted meeting specifications and having
      good margins respect to tolerances. UNIQUE was put into operation for all
      delivery techniques; in particular, as shown by the pre-treatment quality
      assurance results, it enabled accurate and safe delivery of RapidArc plans.

PMID- 21961831
TI  - Perception of emotion in psychiatric disorders: on the possible role of task,
      dynamics, and multimodality.
AB  - Experimental evidence suggests an impairment in emotion perception in numerous
      psychiatric disorders. The results to date are primarily based on research using
      static displays of emotional facial expressions. However, our natural environment
      is dynamic and multimodal, comprising input from various communication channels
      such as facial expressions, emotional prosody, and emotional semantics, to name
      but a few. Thus, one critical open question is whether alterations in emotion
      perception in psychiatric populations are confirmed when testing patients in
      dynamic and multimodal naturalistic settings. Furthermore, the impact task
      demands may exert on results also needs to be reconsidered. Focusing on
      schizophrenia and depression, we review evidence on how emotions are perceived
      from faces and voices in these disorders and examine how experimental task
      demands, stimulus dynamics, and modality may affect study results.

PMID- 21961832
TI  - Attention and social functioning in children with malformations of cortical
      development and stroke.
AB  - Attention and social functioning and their interrelationships have not been
      routinely examined in children with early brain insult (EBI). This study aimed to
      describe attention and social functioning in children with two types of EBI:
      malformations of cortical development (MCD) and stroke. Children diagnosed with
      MCD (n = 14, 6 males) or stroke (n = 14, 8 males) aged 8 to 14 years (M = 12
      years 11 months) completed neuropsychological assessments to examine attention
      processes. Primary caregivers completed a questionnaire to assess executive
      components of children's attention and teachers completed a questionnaire to
      measure children's social functioning. Brain scans (MRI or CT) were coded by a
      pediatric neuroradiologist. Higher rates of impairments in attention and social
      function were found in children with EBI compared with normative expectations.
      Children with MCD experienced more global and clinically significant levels of
      impairment than children with stroke; though impairments were present in both
      groups. A strong association between executive components of attention and social
      function was observed. In addition, complex attention processes were associated
      with social function. The findings emphasize the reciprocity between attention,
      behavior and social outcomes, and the vulnerability of social function following
      EBI.

PMID- 21961833
TI  - Therapeutic utilities of fibroblast growth factor 19.
AB  - INTRODUCTION: Diabetes and associated metabolic conditions have reached pandemic
      proportions worldwide and there is a clear unmet medical need for new therapies
      that are both effective and safe. FGF19 is a distinctive member of the FGF family
      that functions as an endocrine hormone. AREAS COVERED: An up-to-date report on
      the exciting findings related to the involvement of FGF19 in the regulation of
      glucose, bile acid metabolism and energy expenditure. The role of FGF receptors
      in these different activities. The therapeutic potential of FGF19 and the
      engineering opportunities for removing undesirable mitogenic activity. EXPERT
      OPINION: The ability of FGF19 to regulate bile acid homeostasis, gallbladder
      filling and tumor development and its potent ability to normalize glucose, lipid
      and energy homeostasis have made it a potential therapeutic target for the
      treatment of patients with gallstones, cancer and metabolic diseases, among
      others. Its potential utility as a novel therapeutic for both type 1 and type 2
      diabetes is of particular interest. The ability to separate the undesired
      mitogenic activity from its potent metabolic activities has opened new
      opportunities for the development of potential therapeutic molecules based on
      FGF19 in treating various conditions associated with metabolic syndrome.

PMID- 21961834
TI  - PRNP genetic variability and molecular typing of natural goat scrapie isolates in
      a high number of infected flocks.
AB  - One hundred and four scrapie positive and 77 negative goats from 34 Greek mixed
      flocks were analysed by prion protein gene sequencing and 17 caprine scrapie
      isolates from 11 flocks were submitted to molecular isolate typing. For the first
      time, the protective S146 variant was reported in Greece, while the protective
      K222 variant was detected in negative but also in five scrapie positive goats
      from heavily infected flocks. By immunoblotting six isolates, including two goat
      flockmates carrying the K222 variant, showed molecular features slightly
      different from all other Greek and Italian isolates co-analysed, possibly
      suggesting the presence of different scrapie strains in Greece.

PMID- 21961835
TI  - Potentiometric strip cell based on carbon nanotubes as transducer layer: toward
      low-cost decentralized measurements.
AB  - In this study, we developed a potentiometric planar strip cell based on single
      walled carbon nanotubes that aims to exploit the attributes of solid-contact ion
      selective electrodes for decentralized measurements. That is, the ion-selective
      and reference electrodes have been simultaneously miniaturized onto a plastic
      planar substrate by screen-printing and drop-casting techniques, obtaining
      disposable strip cells with satisfactory performance characteristics (i.e., the
      sensitivity is 57.4 +/- 1.3 mV/dec, the response time is <=30 s within the linear
      range from log a(K+) = -5 to -2, and the limit of detection is -6.5), no need of
      maintenance during long dry storage, quick signal stabilization, and light
      insensitivity in short-term measurements. We also show how the new potentiometric
      strip cell makes it possible to perform decentralized and rapid determinations of
      ions in real samples, such as saliva or beverages.

PMID- 21961836
TI  - Association between sexual function and depression in sexually active, mid-aged,
      Peruvian women.
AB  - OBJECTIVE: To determine the association between sexual function and depression in
      sexually active, mid-aged women while controlling for sociodemographical and
      clinical factors. METHODS: Data were analyzed from 335 healthy, sexually active,
      Peruvian women (40-59 years) who simultaneously filled out the Female Sexual
      Function Index (FSFI), the Menopause Rating Scale (MRS), the Beck Depression
      Inventory (BDI) and a general questionnaire containing female/partner data.
      Correlations between the measures of all tools were analyzed. RESULTS: The median
      age of studied women was 49 years; 76.7% had low schooling, 40% were
      postmenopausal and 15.2% used hormone therapy. Regarding the partner, 11% and
      10.5% presented erectile dysfunction and premature ejaculation, respectively.
      FSFI total scores displayed significant correlations with BDI and MRS scores
      (total, psychological and urogenital). Multiple linear regression analysis was
      used to obtain an association model between sexual function and depression,
      explaining 88% of the variance. In this model, sexual function was inversely
      associated with depression, yet confounded by MRS urogenital scores. In addition,
      sexual function was inversely correlated to partner sexual function and to female
      MRS psychological scorings and positively to premenopausal status. CONCLUSION: In
      this mid-aged series, sexual function was significantly associated with
      depression, in addition to hormonal status and partner sexual function.

PMID- 21961837
TI  - Family history of the cancer on the survival of the patients with
      gastrointestinal cancer in northern Iran, using frailty models.
AB  - BACKGROUND: Gastrointestinal (GI) tract cancer is one of the common causes of the
      mortality due to cancer in most developing countries such as Iran. The digestive
      tract is the major organ involved in the cancer. The northern part of the
      country, surrounded the Caspian Sea coast, is well known and the region with
      highest regional incidence of the GI tract cancer. In this paper our aim is to
      study the most common risk factors affecting the survival of the patients
      suffering from GI tract cancer using parametric models with frailty. METHODS:
      This research was a prospective study. Information of 484 cases with GI cancer
      was collected from Babol Cancer Registration Center during 1990-1991. The risk
      factors we studied are age, sex, family history of cancer, marital status,
      smoking status, occupation, race, medication status, education, residence (urban,
      rural), type of cancer, migration status (indigenous, non-native). The studied
      cases were followed up until 2006 for 15 years. Hazard ratio was used to
      interpret the death risk. The effect of the factors in the study on the patients
      survival are studied under a family of parametric models including Weibull,
      Exponential, Log-normal, and the Log-logistic model. The models are fitted using
      with and without frailty. The Akaike information criterion (AIC) was considered
      to compare between competing models. RESULTS: Out of 484 patients in the study,
      321 (66.3%) were males and 163 (33.7%) were females. The average age of the
      patient at the time of the diagnosis was 59 yr and 55 yr for the males and
      females respectively. Furthermore, 359 (74.2%) patients suffered from esophageal,
      110 (22.7%) patients recognized with gastric, and 15 (3.1%) patients with colon
      cancer. Survival rates after 1, 3, and 5 years of the diagnosis were 24%, 16%,
      and 15%, respectively. We found that the family history of the cancer is a
      significant factor on the death risk under all statistical models in the study.
      The comparison of AIC using the Cox and parametric models showed that the overall
      fitting was improved under parametric models (with and without frailty). Among
      parametric models, we found better performance for the log-logistic model with
      gamma frailty than the others. Using this model, gender and the family history of
      the cancer were found as significant predictors. CONCLUSIONS: Results suggested
      that the early preventative care for patients with family history of the cancer
      may decrease the risk of the death in the patients with GI cancer. The gender
      appeared to be an important factor as well so that men experiencing lower risk of
      death than the women in the study. Since the proportionality assumption of the
      Cox model was not held (p = 0.0014), the Cox regression model was not an
      appropriate choice for analysing our data.

PMID- 21961842
TI  - Toward interaction of sensitizer and functional moieties in hole-transporting
      materials for efficient semiconductor-sensitized solar cells.
AB  - Sb(2)S(3)-sensitized mesoporous-TiO(2) solar cells using several conjugated
      polymers as hole-transporting materials (HTMs) are fabricated. We found that the
      cell performance was strongly correlated with the chemical interaction at the
      interface of Sb(2)S(3) as sensitizer and the HTMs through the thiophene moieties,
      which led to a higher fill factor (FF), open-circuit voltage (V(oc)), and short
      circuit current density (J(sc)). With the application of PCPDTBT (poly(2,6-(4,4
      bis-(2-ethylhexyl)-4H-cyclopenta[2,1-b;3,4-b']dithiophene)-alt-4,7(2,1,3
      benzothiadiazole)) as a HTM in a Sb(2)S(3)-sensitized solar cell, overall power
      conversion efficiencies of 6.18, 6.57, and 6.53% at 100, 50, and 10% solar
      irradiation, respectively, were achieved with a metal mask.

PMID- 21961843
TI  - Effect of introduction of chondroitin sulfate into polymer-peptide conjugate
      responding to intracellular signals.
AB  - We recently developed a novel tumor-targeted gene delivery system responding to
      hyperactivated intracellular signals. Polymeric carrier for gene delivery
      consists of hydrophilic neutral polymer as main chains and cationic peptide
      substrate for target enzyme as side chains, and was named polymer-peptide
      conjugate (PPC). Introduction of chondroitin sulfate (CS), which induces receptor
      medicated endocytosis, into polymers mainly with a high cationic charge density
      such as polyethylenimine can increase tumor-targeted gene delivery. In the
      present study, we examined whether introduction of CS into PPC containing five
      cationic amino acids can increase gene expression in tumor cells. Size and zeta
      potential of plasmid DNA (pDNA)/PPC/CS complex were <200 nm and between -10 and 
      15 mV, respectively. In tumor cell experiments, pDNA/PPC/CS complex showed lower
      stability and gene regulation, compared with that of pDNA/PPC. Moreover, no
      difference in gene expression was identified between positive and negative
      polymer. These results were caused by fast disintegration of pDNA/PPC/CS
      complexes in the presence of serum. Thus, we suggest that introduction of
      negatively charged CS into polymers with a low charge density may lead to low
      stability and gene regulation of complexes.

PMID- 21961845
TI  - Entropy of liquid water from ab initio molecular dynamics.
AB  - We have computed the entropy of liquid water using a two-phase thermodynamic
      model and trajectories generated by ab initio molecular dynamics simulations. We
      present the results obtained with semilocal, hybrid, and van der Waals density
      functionals. We show that in all cases, at the experimental equilibrium density
      and at temperatures in the vicinity of 300 K, the computed entropies are
      underestimated, with respect to experiment, and the liquid exhibits a degree of
      tetrahedral order higher than in experiments. The underestimate is more severe
      for the PBE and PBE0 functionals than for several van der Waals functionals.

PMID- 21961844
TI  - Association study of B-cell marker gene polymorphisms in European Caucasian
      patients with systemic sclerosis.
AB  - BACKGROUND: BANK1 and BLK B-cell genetic markers have been reproducibly and
      convincingly found to contribute to susceptibility to systemic sclerosis (SSc).
      OBJECTIVES: To determine whether other B-cell genetic markers including CD19,
      CD20, CD22 and CD24 polymorphisms affect susceptibility to SSc in the European
      Caucasian population. METHODS: A case-control study was performed in 900 patients
      with SSc and 1034 healthy controls. Among the whole SSc population, 304 (34%) had
      the diffuse cutaneous subtype, 551 (61%) had the limited cutaneous subtype, 732
      (81%) were positive for antinuclear antibodies , 331 (37%) were positive for
      anticentromere antibodies and 228 (25%) for the topo-isomerase I. Genotyping has
      been performed for CD19 rs35979293, CD19 rs2904880, CD20 rs7126354, CD20
      rs3802954, CD20 rs105146, CD20 rs4939364, CD22 rs10406069, CD22 rs10413500, CD22
      rs10419538, CD22 rs34826052 and CD24 ins-del polymorphisms. RESULTS: Genotype
      frequencies were at the Hardy-Weinberg equilibrium in the control population for
      all the SNPs investigated and observed frequencies were very similar to those
      expected in the European population. Allelic and genotypic frequencies for all
      these tested SNPs were found to be similar in SSc patients and controls.
      Moreover, subphenotype analyses in particular for subgroups having the diffuse
      cutaneous subset or topo-isomerase I positive antibodies, which are the most
      associated with BANK1 variants, did not detect any difference between SSc
      patients and controls. CONCLUSIONS: These results obtained through a large cohort
      of European caucasian patients with SSc do not support the contribution of CD19,
      CD20, CD22, CD24 variants to the genetic susceptibility of SSc.

PMID- 21961846
TI  - Filmless versus film-based systems in radiographic examination costs: an activity
      based costing method.
AB  - BACKGROUND: Since the shift from a radiographic film-based system to that of a
      filmless system, the change in radiographic examination costs and costs structure
      have been undetermined. The activity-based costing (ABC) method measures the cost
      and performance of activities, resources, and cost objects. The purpose of this
      study is to identify the cost structure of a radiographic examination comparing a
      filmless system to that of a film-based system using the ABC method. METHODS: We
      calculated the costs of radiographic examinations for both a filmless and a film
      based system, and assessed the costs or cost components by simulating
      radiographic examinations in a health clinic. The cost objects of the
      radiographic examinations included lumbar (six views), knee (three views), wrist
      (two views), and other. Indirect costs were allocated to cost objects using the
      ABC method. RESULTS: The costs of a radiographic examination using a filmless
      system are as follows: lumbar 2,085 yen; knee 1,599 yen; wrist 1,165 yen; and
      other 1,641 yen. The costs for a film-based system are: lumbar 3,407 yen; knee
      2,257 yen; wrist 1,602 yen; and other 2,521 yen. The primary activities were
      "calling patient," "explanation of scan," "take photographs," and "aftercare" for
      both filmless and film-based systems. The cost of these activities cost
      represented 36.0% of the total cost for a filmless system and 23.6% of a film
      based system. CONCLUSIONS: The costs of radiographic examinations using a
      filmless system and a film-based system were calculated using the ABC method. Our
      results provide clear evidence that the filmless system is more effective than
      the film-based system in providing greater value services directly to patients.

PMID- 21961847
TI  - How the comparison of age-related macular degeneration treatments trial results
      will impact clinical care.
AB  - PURPOSE: To provide a perspective on the impact of the Comparison of Age-related
      Macular Degeneration Treatments Trial (CATT) on future clinical practices.
      DESIGN: Interpretation of trial outcomes relative to clinical use of neovascular
      age-related macular degeneration (AMD) treatments, assessment of the influence of
      study design and execution on results, and review of unanalyzed safety data in
      the online supplement. METHODS: Expert opinion. RESULTS: The CATT study supports
      the selection of either ranibizumab or bevacizumab for treatment of AMD based on
      factors other than efficacy, such as cost, because monthly administration of
      bevacizumab was noninferior to the reference treatment of monthly ranibizumab in
      improving visual acuity at 1 year. Visual acuity results for bevacizumab as
      needed were inconclusive for noninferiority relative to monthly administration of
      either drug. The secondary outcome of decrease in thickness at the foveal center
      as measured by time-domain optical coherence tomography significantly favored the
      monthly ranibizumab group vs the bevacizumab-as-needed group but is more
      difficult to interpret as it did not correlate with visual acuity and is less
      appropriate for a noninferiority design. Bevacizumab groups had a statistically
      higher observed risk of serious adverse events; however, scrutiny of the online
      supplements shows similar numbers of cardiac and neurologic events in bevacizumab
      and ranibizumab users. Information regarding fellow eye treatment with anti-VEGF
      agents was not given. CONCLUSIONS: CATT provides the first level I evidence for
      bevacizumab in a large number of patients with neovascular AMD. The trial
      supports use of either drug as primary therapy and suggests that modification of
      monthly dosing regimens is feasible. A difference in cardiovascular safety
      between the 2 drugs was not apparent on inspection of the supplementary safety
      data.

PMID- 21961848
TI  - An assessment of the health and economic burdens of glaucoma.
AB  - PURPOSE: To bring together information concerning the epidemiology and the
      economic and individual burdens of glaucoma. DESIGN: Interpretive essay. METHODS:
      Review and synthesis of selected literature published from 1991 through December
      2010. RESULTS: An estimated 3% of the global population over 40 years of age
      currently has glaucoma, the majority of whom are undiagnosed. Vision loss from
      glaucoma has a significant impact on health-related quality of life even in the
      early stages of disease. The overall burden increases as glaucomatous damage and
      vision loss progress. The economic burden of glaucoma is significant and
      increases as the disease worsens. CONCLUSIONS: Early identification and treatment
      of patients with glaucoma and those with ocular hypertension at high risk of
      developing vision loss are likely to reduce an individual's loss of health
      related quality of life as well as the personal and societal economic burdens.

PMID- 21961849
TI  - Outcomes of a protocol-based management for zone 1 retinopathy of prematurity:
      the Indian Twin Cities ROP Screening Program report number 2.

PMID- 21961851
TI  - Presentation to publication.

PMID- 21961853
TI  - Diagnostic pitfalls in spine surgery: masqueraders of surgical spine disease.
AB  - Disorders of the spine are common in clinical medicine, and spine surgery is
      being performed with increasing frequency in the US. Although many patients with
      an established diagnosis of a true surgically treatable lesion are referred to a
      neurosurgeon, the evaluation of patients with spinal disorders can be complex and
      fraught with diagnostic pitfalls. While "common conditions are common," astute
      clinical acumen and vigilance are necessary to identify lesions that masquerade
      as surgically treatable spine disease that can lead to erroneous diagnosis and
      treatment. In this review, the authors discuss musculoskeletal, peripheral nerve,
      metabolic, infectious, inflammatory, and vascular conditions that mimic the
      syndromes produced by surgical lesions. It is possible that nonsurgical and
      surgical conditions coexist at times, complicating treatment plans and natural
      histories. Awareness of these diagnoses can help reduce diagnostic error, thereby
      avoiding the morbidity and expense associated with an unnecessary operation.

PMID- 21961852
TI  - Creating opal-templated continuous conducting polymer films with ultralow
      percolation thresholds using thermally stable nanoparticles.
AB  - We propose a novel and robust strategy for creating continuous conducting polymer
      films with ultralow percolation thresholds using polymer-coated gold
      nanoparticles (Au NPs) as surfactant. Continuous poly(triphenylamine) (PTPA)
      films of high internal phase polymeric emulsions were fabricated using an
      assembly of cross-linked polystyrene (PS) colloidal particles as template.
      Polymer-coated Au NPs were designed to be thermally stable even above 200 
      degrees C and neutral to both the PS and PTPA phases. Therefore, the Au NPs
      localize at the PS/PTPA interface and function as surfactant to efficiently
      produce a continuous conducting PTPA polymer film with very low percolation
      thresholds. The volume fraction threshold for percolation of the PTPA phase with
      insulating PS colloids (as measured by electron microscopy and conductivity
      measurements) was found to be 0.20. In contrast, with the addition of an
      extremely low volume fraction (phi(p) = 0.35 vol %) of surfactant Au NPs, the
      volume fraction threshold for percolation of the PTPA phase was dramatically
      reduced to 0.05. The SEM and TEM measurements clearly demonstrated the formation
      of a continuous PTPA phase within the polyhedral phase of PS colloids. To
      elucidate the influence of the nanoparticle surfactant on the blend films, the
      morphology and conductivity of the blends at different PS colloid/PTPA volume
      ratios were carefully characterized as a function of the Au NP concentration. Our
      approach provides a methodology for a variety of applications that require a
      continuous phase for the transport of molecular species, ions, or electrons at
      low concentrations and a second phase for mechanical support or the conduction of
      a separate species.

PMID- 21961854
TI  - Complications related to instrumentation in spine surgery: a prospective
      analysis.
AB  - OBJECT: Prospective examination of perioperative complications in spine surgery
      is limited in the literature. The authors prospectively collected data on
      patients who underwent spinal fusion at a tertiary care center and evaluated the
      effect of spinal fusion and comorbidities on perioperative complications.
      METHODS: Between May and December 2008 data were collected prospectively in 248
      patients admitted to the authors' institution for spine surgery. The 202 patients
      undergoing spine surgery with instrumentation were further analyzed in this
      report. Perioperative complications occurring within the initial 30 days after
      surgery were included. All adverse occurrences, whether directly related to
      surgery, were included in the analysis. RESULTS: Overall, 114 (56.4%) of 202
      patients experienced at least one perioperative complication. Instrumented
      fusions were associated with more minor complications (p = 0.001) and more
      overall complications (0.0024). Furthermore, in the thoracic and lumbar spine,
      complications increased based on the number of levels fused. Advanced patient age
      and certain comorbidities such as diabetes, cardiac disease, or a history of
      malignancy were also associated with an increased incidence of complications.
      CONCLUSIONS: Using a prospective methodology with a broad definition of
      complications, the authors report a significantly higher perioperative incidence
      of complications than previously indicated after spinal fusion procedures. Given
      the increased application of instrumentation, especially for degenerative
      disease, a better estimate of clinically relevant surgical complications could
      aid spine surgeons and patients in an individualized complication index to
      facilitate a more thorough risk-benefit analysis prior to surgery.

PMID- 21961855
TI  - Accuracy of the freehand technique for 3 fixation methods in the C-2 vertebrae.
AB  - OBJECT: Intraoperative imaging often does not provide adequate visualization to
      ensure safe placement of screws. Therefore, the authors investigated the accuracy
      of a freehand technique for placement of pars, pedicle, and intralaminar screws
      in C-2. METHODS: Sixteen cadaveric specimens were instrumented freehand by 2
      experienced cervical spine surgeons with either a pars or pedicle screw, and
      bilateral intralaminar screws. The technique was based on anatomical starting
      points and published screw trajectories. A pedicle finder was used to establish
      the trajectory, followed by tapping, palpation, and screw placement. After
      placement of all screws (16 pars screws, 16 pedicle screws, and 32 intralaminar
      screws), the C-2 segments were disarticulated, radiographed in anteroposterior,
      lateral, and axial planes, and meticulously inspected by another spine surgeon to
      determine the nature and presence of any defects. RESULTS: A total of 64 screws
      were evaluated in this study. Pars screws exhibited 2 critical defects (1 in the
      foramen transversarium and 1 in the C2-3 facet) and an insignificant dorsal
      cortex breech, for an overall accuracy rate of 81.3%. Pedicle screws demonstrated
      only 1 insignificant violation (inferior facet/medial cortex intrusion of 1 mm)
      with an accuracy rate of 93.8%, and intralaminar screws demonstrated 3
      insignificant violations (2 in the ventral canal, 1 in the caudad lamina breech)
      for an accuracy rate of 90.6%. Pars screws had significantly more critical
      violations than intralaminar screws (p = 0.041). CONCLUSIONS: Instrumentation of
      the C-2 vertebrae using the freehand technique for insertion of pedicle and
      intralaminar screws showed a high success rate with no critical violations. Pars
      screw insertion was not as reliable, with 2 critical violations from a total of
      16 placements. The freehand technique appears to be a safe and reliable method
      for insertion of C-2 pedicle and intralaminar screws.

PMID- 21961856
TI  - Anterior corpectomy versus posterior laminoplasty: is the risk of postoperative C
      5 palsy different?
AB  - OBJECT: Both anterior cervical corpectomy and fusion (ACCF) and laminoplasty are
      effective treatments for selected cases of cervical stenosis. Postoperative C-5
      palsies may occur with either anterior or posterior decompressive procedures;
      however, a direct comparison of C-5 palsy rates between the 2 approaches is not
      present in the literature. The authors sought to compare the C-5 palsy rate of
      ACCF versus laminoplasty. METHODS: The authors conducted a retrospective review
      of 31 ACCF (at C-4 or C-5) and 31 instrumented laminoplasty cases performed to
      treat cervical stenosis. The demographics of the groups were similar except for
      age (ACCF group mean age 53 years vs laminoplasty group mean age 62 years, p =
      0.002). The mean number of levels treated was greater in the laminoplasty cohort
      (3.87 levels) than in the ACCF cohort (2.74 levels, p < 0.001). The mean
      preoperative Nurick grade of the laminoplasty cohort (2.61) was higher than the
      mean preoperative Nurick grade of the ACCF cohort (1.10, p < 0.001). RESULTS: The
      overall clinical follow-up rate was 100%. The mean overall clinical follow-up was
      15 months. There were no significant differences in the estimated blood loss or
      length of stay between the 2 groups (p > 0.05). There was no statistical
      difference between the complication or reoperation rates between the 2 groups (p
      = 0.184 and p = 0.238). There were 2 C-5 nerve root pareses in each group. Three
      of the 4 patients recovered full deltoid function, and the fourth patient
      recovered nearly full deltoid function at final follow-up. There was no
      statistical difference in the rate of deltoid paresis (6.5%) between the 2 groups
      (p = 1). CONCLUSIONS: Both ACCF and laminoplasty are effective treatments for
      patients with cervical stenosis. The authors found no difference in the rate of
      deltoid paresis between ACCF and laminoplasty to treat cervical stenosis.

PMID- 21961857
TI  - Complications associated with the treatment for spinal ependymomas.
AB  - Spinal cord ependymomas are rare neoplasms, comprising approximately 5% of all
      CNS tumors and 15% of all spinal cord tumors. Although surgery was once reserved
      for diagnosis alone, the evolution of surgical practices has elevated resection
      to the treatment of choice for these lesions. While technological advances
      continue to improve the capacity for gross-total resections and thus decrease the
      risk of recurrence, ependymoma spinal surgery still contains a variety of
      potential complications. The presence of neurological deficits and deterioration
      are not uncommonly associated with spinal cord ependymoma surgery, including
      sensory loss, dorsal column dysfunction, dysesthetic syndrome, and bowel and
      bladder dysfunction, particularly in the immediate postoperative period. Surgical
      treatment may also lead to wound complications and CSF leaks, with increased risk
      when radiotherapy has been involved. Radiation therapy may also predispose
      patients to radiation myelopathy and ultimately result in neurological damage.
      Additionally, resections of spinal ependymomas have been associated with
      postoperative spinal instability and deformities, particularly in the pediatric
      population. Despite the advances in microsurgical techniques and intraoperative
      cord monitoring modalities, there remain a number of serious complications
      related to the treatment of spinal ependymoma tumors. Identification and
      acknowledgment of these potential problems may assist in their prevention, early
      detection, and increased quality of life for patients afflicted with this
      disease.

PMID- 21961858
TI  - Management considerations and strategies to avoid complications associated with
      the thoracoscopic approach for corpectomy.
AB  - The thoracoscopic approach to the anterior spine is a practical and valuable
      means of approaching ventral spinal lesions but demands advanced technical skills
      and fine hand-eye coordination that is usually acquired with experience. A mutual
      understanding of all the ventilatory and surgical steps allows for an organized
      orchestration between the anesthesiologist and surgeon, which ultimately helps
      minimize potential complications. Despite a concerted effort by all involved to
      avoid risks, thoracoscopic surgery is associated with complications for which the
      surgical team should be cognizant. In this paper, the authors detail the
      operative technique of vertebral corpectomy and interbody fusion via the
      thoracoscopic approach for the treatment of ventral spinal pathology involving
      the thoracic and lower lumbar spine, discuss complications known to occur with
      the thoracoscopic approach, and present means to help avoid them.

PMID- 21961859
TI  - Management of incidental durotomy in minimally invasive spine surgery.
AB  - OBJECT: Unintended durotomy is one of the most common complications in spine
      surgery that may lead to serious complications if not recognized or treated
      properly. There are few reports on the management of durotomies incurred during
      minimally invasive spine surgery (MISS). The authors describe their experience in
      a series of consecutive MISS patients with unintended durotomies. METHODS: All
      patients who underwent MISS by the senior author between August 2006 and February
      2011 were retrospectively reviewed, and cases with unintended durotomies were
      identified. A case-control study was carried out comparing patient demographics
      and perioperative data between patients with and without durotomy. Surgical
      technique, including a proposed algorithm for management of durotomies, is
      described. RESULTS: Unintended durotomy occurred in 53 (9.4%) of 563 patients.
      The mean age at surgery was 60.7 years (range 30-85 years). Previous surgery at
      the same level was performed in 5 patients (9.4%). Two patients underwent
      posterior cervical surgery, and 51 patients underwent posterior lumbar surgery.
      Decompression alone was performed in 32 patients (60.4%), and fusion was
      performed in 21 patients (39.6%). The mean operative time was 105 minutes in the
      decompression group and 310 minutes in the fusion group (p < 0.001). Estimated
      blood loss was 60 ml in the decompression group and 381 ml in the fusion group (p
      < 0.001). The hospital length of stay was 52 hours in the decompression group and
      106 hours in the fusion group (p < 0.001). The mean follow-up was 310 days, and
      there were no cases of cutaneous CSF fistula, pseudomeningocele, or other
      complications referable to durotomy in either group. Risk factors identified for
      durotomy included previous operation at the same level (p = 0.019) and operation
      in the lumbar spine region (p = 0.001). CONCLUSIONS: In the authors' consecutive
      series of patients undergoing MISS, an unintended durotomy was associated with
      fewer complications than previously reported for open spinal surgery. The authors
      propose a simple management algorithm that includes early mobilization and
      results in excellent clinical outcomes with no incidence of postoperative
      cutaneous CSF fistula or other complications.

PMID- 21961860
TI  - Abdominal complications following posterior spinal fusion in patients with
      previous abdominal surgeries.
AB  - Perioperative abdominal complications associated with spine surgery are rare.
      Although most known abdominal complications occur in conjunction with anterior
      spinal fusions, there is a paucity of reports reviewing abdominal complications
      occurring with posterior spinal fusions. The authors review 4 patients who
      experienced a perioperative abdominal complication following a posterior spinal
      fusion. In each of these patients, a history of abdominal surgery is present.
      Given the physiological changes that occur with surgery in the prone position,
      patients with previous abdominal surgeries are at risk for developing abdominal
      complications in the perioperative period.

PMID- 21961861
TI  - Revision strategies for AxiaLIF.
AB  - OBJECT: Paracoccygeal transsacral fixation is a novel percutaneous technique for
      arthrodesis of L5-S1 and L4-5 (Axial Lumbar Interbody Fusion [AxiaLIF]). There
      are no reports on feasible revision strategies. The goal of this paper is to
      analyze the surgical details of failed AxiaLIF constructs and to describe
      revision strategies. METHODS: The medical charts, operative records, and imaging
      studies of 5 patients with failed multisegment instrumentation using the AxiaLIF
      device were reviewed. RESULTS: AxiaLIF constructs were revised in 5 patients with
      a mean age of 58.4 years. All AxiaLIF devices were part of multisegment fusion
      constructs for revision surgery and were revised an average of 15 months after
      implantation. Two AxiaLIF devices were percutaneously retrieved; one because of
      excessive bone resorption around the AxiaLIF screw, and the other because of
      chronic hardware infection. In these 2 patients, the anterior column was
      subsequently stabilized via anterior lumbar interbody fusion. In the other 3
      patients, the AxiaLIF device was left in situ. In 2 of these patients the
      anterior column was stabilized with bilateral L5-S1 posterior lumbar interbody
      fusion, and in the remaining patient with L4-5 instability the posterior
      instrumentation only was revised. Revision surgeries were well tolerated. One
      patient suffered from a wound dehiscence of the back wound. CONCLUSIONS: AxiaLIF
      devices are safely retrieved using percutaneous technique. Both anterior and
      posterior revision strategies may be used to achieve anterior column fixation.

PMID- 21961862
TI  - Abdominal wall paresis as a complication of minimally invasive lateral transpsoas
      interbody fusion.
AB  - OBJECT: The minimally invasive lateral transpsoas approach for interbody fusion
      has been increasingly employed to treat various spinal pathological entities.
      Gaining access to the retroperitoneal space and traversing the abdominal wall
      poses a risk of injury to the major nervous structures. Nerve injury of the
      abdominal wall can potentially lead to paresis of the abdominal musculature and
      bulging of the abdominal wall. Abdominal wall nerve injury resulting from the
      minimally invasive lateral retroperitoneal transpsoas approach has not been
      previously reported. The authors describe a case series of patients presenting
      with paresis and bulging of the abdominal wall after undergoing a minimally
      invasive lateral retroperitoneal approach. METHODS: The authors retrospectively
      reviewed all patients who underwent a minimally invasive lateral transpsoas
      approach for interbody fusion and in whom development of abdominal paresis
      developed; the patients were treated at 4 institutions between 2006 and 2010. All
      data were recorded including demographics, diagnosis, operative procedure,
      positioning, hospital course, follow-up, and complications. The onset, as well as
      resolution of the abdominal paresis, was reviewed. RESULTS: The authors
      identified 10 consecutive patients in whom abdominal paresis developed after
      minimally invasive lateral transpsoas spine surgery out of a total of 568
      patients. Twenty-nine interbody levels were fused (range 1-4 levels/patient).
      There were 4 men and 6 women whose mean age was 54.1 years (range 37-66 years).
      All patients presented with abdominal paresis 2-6 weeks postoperatively. In 8 of
      the 10 patients, abdominal wall paresis had resolved by the 6-month follow-up
      visit. Two patients only had 1 and 4 months of follow-up. No long-term sequelae
      were identified. CONCLUSIONS: Abdominal wall paresis is a rare but known
      potential complication of abdominal surgery. The authors report the first case
      series associated with the minimally invasive lateral transpsoas approach.

PMID- 21961863
TI  - Cervical juxtafacet cyst after anterior cervical discectomy and fusion.
AB  - Anterior cervical discectomy and fusion (ACDF) is a common neurosurgical
      procedure, and the benefits, long-term outcomes, and complications are well
      described in the literature. The development of a juxtafacet joint cyst resulting
      in radiculopathy is a rare outcome after ACDF and merits further description. The
      authors describe a patient in whom a juxtafacet joint cyst developed after ACDF
      procedures, resulting in surgical intervention. When a juxtafacet joint cyst
      develops after ACDF, symptoms can include radiculopathy, neck pain, and
      neurological symptoms such as paresthesias and motor weakness. The presence of a
      juxtafacet joint cyst implies instability in that region of the spine. Patients
      with this pathological entity may require decompression of neural elements and
      fusion across the segment involved with the cyst.

PMID- 21961864
TI  - Complication management with minimally invasive spine procedures.
AB  - Spine surgery as we know it has changed dramatically over the past 2 decades.
      More patients are undergoing minimally invasive procedures. Surgeons are becoming
      more comfortable with these procedures, and changes in technology have led to
      several new approaches and products to make surgery safer for patients and
      improve patient outcomes. As more patients undergo minimally invasive spine
      surgery, more long-term outcome and complications data have been collected. The
      authors describe the common complications associated with these minimally
      invasive surgical procedures and delineate management options for the spine
      surgeon.

PMID- 21961865
TI  - Idiopathic intracranial hypertension following spinal deformity surgery in
      children.
AB  - Idiopathic intracranial hypertension (IIH) after pediatric spinal deformity
      surgery has not been previously reported. The authors conducted a retrospective
      analysis of more than 1500 pediatric spinal surgeries performed between 1992 and
      2011. From their analysis, they report on 3 adolescent patients who underwent
      uncomplicated segmental spinal instrumentation for pediatric spinal deformity
      correction and subsequently developed features of IIH. The common variables in
      these 3 patients were adolescent age, spinal deformity, being overweight, symptom
      onset within 2 weeks postoperatively, significant estimated blood loss, and
      intraoperative use of epsilon-aminocaproic acid (antifibrinolytic) injection. The
      authors postulate that the development of IIH could be the result of venous
      outflow obstruction due to derangement of the epidural venous plexus during
      surgery. The use of epsilon-aminocaproic acid could potentially have the risk of
      causing IIH, probably mediated through hyperfibrinogenemia, although there have
      not been published cases in the neurosurgical, orthopedic, cardiac, or general
      surgical literature. Idiopathic intracranial hypertension after spinal deformity
      correction is a condition that should be recognized by neurosurgeons and
      orthopedic surgeons, because appropriate intervention with early medical therapy
      can lead to a satisfactory clinical outcome.

PMID- 21961866
TI  - Complications and outcomes after spinal deformity surgery in the elderly: review
      of the existing literature and future directions.
AB  - OBJECT: The elderly population (age > 60 years) is the fastest-growing age group
      in the US. Spinal deformity is a major problem affecting the elderly and,
      therefore, the demand for surgery for spinal deformity is becoming increasingly
      prevalent in elderly patients. Much of the literature on surgery for adult
      deformity focuses on patients who are younger than 60 years, and therefore there
      is limited information about the complications and outcomes of surgery in the
      elderly population. In this study, the authors undertook a review of the
      literature on spinal deformity surgery in patients older than 60 years. The
      authors discuss their analysis with a focus on outcomes, complications,
      discrepancies between individual studies, and strategies for complication
      avoidance. METHODS: A systematic review of the MEDLINE and PubMed databases was
      performed to identify articles published from 1950 to the present using the
      following key words: "adult scoliosis surgery" and "adult spine deformity
      surgery." Exclusion criteria included patient age younger than 60 years. Data on
      major Oswestry Disability Index (ODI) scores, visual analog scale (VAS) scores,
      patient-reported outcomes, and complications were recorded. RESULTS: Twenty-two
      articles were obtained and are included in this review. The mean age was 74.2
      years, and the mean follow-up period was 3 years. The mean preoperative ODI was
      48.6, and the mean postoperative reduction in ODI was 24.1. The mean preoperative
      VAS score was 7.7 with a mean postoperative decrease of 5.2. There were 311
      reported complications for 815 patients (38%) and 5 deaths for 659 patients (<
      1%). CONCLUSIONS: Elderly patient outcomes were inconsistent in the published
      studies. Overall, most elderly patients obtained favorable outcomes with low
      operative mortality following surgery for adult spinal deformity.

PMID- 21961867
TI  - Minimally invasive lateral lumbar interbody fusion and transpsoas approach
      related morbidity.
AB  - OBJECT: Recently, the minimally invasive, lateral retroperitoneal, transpsoas
      approach to the thoracolumbar spinal column has been described by various
      authors. This is known as the minimally invasive lateral lumbar interbody fusion.
      The purpose of this study is to elucidate the approach-related morbidity
      associated with the minimally invasive transpsoas approach to the lumbar spine.
      To date, there have been only a couple of reports regarding the morbidity of the
      transpsoas muscle approach. METHODS: A nonrandomized, prospective study utilizing
      a self-reported patient questionnaire was conducted between January 2006 and June
      2008 at Northwestern University. Data were collected in 53 patients with a follow
      up period ranging from 6 months to 3.5 years. Only 2 patients were lost to follow
      up. RESULTS: Thirty-six percent (19 of 53) of patients reported subjective hip
      flexor weakness, 25% (13 of 53) anterior thigh numbness, and 23% (12 of 53)
      anterior thigh pain. However, 84% of the 19 patients reported complete resolution
      of their subjective hip flexor weakness by 6 months, and most experienced
      improved strength by 8 weeks. Of those reporting anterior thigh numbness and
      pain, 69% and 75% improved to their baseline function by the 6-month follow-up
      evaluations, respectively. All patients with self-reported subjective hip flexor
      weakness underwent examinations during subsequent clinic visits after surgery;
      however, these examinations did not confirm a motor deficit less than Grade 5.
      Subset analysis showed that the L3-4 and L4-5 levels were most often affected.
      CONCLUSIONS: The minimally invasive, transpsoas muscle approach to the lumbar
      spine has a number of advantages. The data show that a percentage of the patients
      undergoing the transpsoas approach will have temporary sensory and motor symptoms
      related to this approach. The majority of the symptoms are thought to be related
      to psoas muscle inflammation and/or stretch injury to the genitofemoral nerve due
      to the surgical corridor traversed during the operation. No major injuries to the
      lumbar plexus were encountered. It is important to educate patients prior to
      surgery of the possibility of these largely transient symptoms.

PMID- 21961868
TI  - Strategies to avoid wrong-site surgery during spinal procedures.
AB  - Wrong-site surgery (WSS) is a rare occurrence that can have devastating
      consequences for patient care. There are several factors inherent to spine
      surgery that increase the risk of WSS compared with other types of surgery. Not
      only can a surgeon potentially operate on the wrong side of the spine or the
      wrong level, but there are unique issues related to spinal localization that can
      be challenging for even the most experienced clinicians. The following review
      discusses important issues that can help prevent WSS during spinal procedures.

PMID- 21961869
TI  - Complication avoidance and management in anterior lumbar interbody fusion.
AB  - The goal of this study was to review the literature to compare strategies for
      avoiding and treating complications from anterior lumbar interbody fusion (ALIF),
      and thus provide a comprehensive aid for spine surgeons. A thorough review of
      databases from the US National Library of Medicine and the National Institutes of
      Health was conducted. The complications of ALIF addressed in this paper include
      pseudarthrosis and subsidence, vascular injury, retrograde ejaculation, ileus,
      and lymphocele (chyloretroperitoneum). Strategies identified for improving fusion
      rates included the use of frozen rather than freeze-dried allograft, cage
      instrumentation, and bone morphogenetic protein. Lower cage heights appear to
      reduce the risk of subsidence. The most common vascular injury is venous
      laceration, which occurs less frequently when using nonthreaded interbody grafts
      such as iliac crest autograft or femoral ring allograft. Left iliac artery
      thrombosis is the most common arterial injury, and its occurrence can be
      minimized by intermittent release of retraction intraoperatively. The risk of
      retrograde ejaculation is significantly higher with laparoscopic approaches, and
      thus should be avoided in male patients. Despite precautionary measures,
      complications from ALIF may occur, but treatment options do exist. Bowel
      obstruction can be treated conservatively with neostigmine or with decompression.
      In cases of postoperative lymphocele, resolution can be attained by creating a
      peritoneal window. By recognizing ways to minimize complications, the spine
      surgeon can safely use ALIF procedures.

PMID- 21961870
TI  - Avoiding pitfalls in anterior screw fixation for type II odontoid fractures.
AB  - Anterior screw fixation of Type II odontoid fractures provides immediate
      stabilization of the cervical spine while preserving C1-2 motion. This technique
      has a high fusion rate, but can be technically challenging. The authors identify
      key points that should be taken into account to maximize the chance for a
      favorable outcome. Keys to success include proper patient and fracture selection,
      identification of suitable screw entry point and correct screw trajectory,
      achieving bicortical purchase, and placing 2 screws when feasible and applicable.
      The authors review the operative technique and present guidance on appropriate
      patient selection and common pitfalls in anterior screw fixation, with strategies
      for avoiding complications.

PMID- 21961871
TI  - Clinically relevant complications related to pedicle screw placement in
      thoracolumbar surgery and their management: a literature review of 35,630 pedicle
      screws.
AB  - OBJECT: The technique of pedicle screw insertion is a mainstay of spinal
      instrumentation. Some of its potential complications are clinically relevant and
      may require reoperation or further postoperative care. METHODS: A literature
      search was performed using MEDLINE (between 1999 and June 2011) for studies on
      pedicle screw placement in thoracolumbar surgery. The authors included randomized
      controlled trials, case-control studies, and case series (>= 20 patients) from
      the English-, German-, and French-language literature. The authors assessed study
      type, the number of patients, the anatomical area, the number of pedicle screws,
      duration of follow-up, type of pedicle screw placement, incidence of
      complications, and type of complication. The management of specific complications
      is discussed. RESULTS: Thirty-nine articles with 46 patient groups were reviewed
      with a total of 35,630 pedicle screws. One study was a randomized controlled
      trial, 8 were case-control studies, and the remaining articles were case series.
      Dural lesions and irritation of nerve roots were reported in a mean of 0.18% and
      0.19% per pedicle screws, respectively. Thirty-two patients in 10 studies (of
      5654 patients from all 39 studies) required further revision surgeries for
      misplaced pedicle screws causing neurological problems. None of the analyzed
      studies reported vascular complications, and only 2 studies reported visceral
      complications of clinical significance. CONCLUSIONS: Pedicle screw placement in
      the thoracolumbar region is a safe procedure with an overall high accuracy and a
      very low rate of clinically relevant complications.

PMID- 21961872
TI  - Pedicle screw loosening in dynamic stabilization: incidence, risk, and outcome in
      126 patients.
AB  - OBJECT: The long-term outcome of lumbar dynamic stabilization is uncertain. This
      study aimed to investigate the incidence, risk factors, and outcomes associated
      with screw loosening in a dynamic stabilization system. METHODS: The authors
      conducted a retrospective review of medical records, radiological studies, and
      clinical evaluations obtained in consecutive patients who underwent 1- or 2-level
      lumbar dynamic stabilization and were followed up for more than 24 months.
      Loosening of screws was determined on radiography and CT scanning. Radiographic
      and standardized clinical outcomes, including the visual analog scale (VAS) and
      Oswestry Disability Index (ODI) scores, were analyzed with a focus on cases in
      which screw loosening occurred. RESULTS: The authors analyzed 658 screws in 126
      patients, including 54 women (42.9%) and 72 men (57.1%) (mean age 60.4 +/- 11.8
      years). During the mean clinical follow-up period of 37.0 +/- 7.1 months, 31
      screws (4.7%) in 25 patients (19.8%) were shown to have loosened. The mean age of
      patients with screw loosening was significantly higher than those without
      loosening (64.8 +/- 8.8 vs 59.3 +/- 12.2, respectively; p = 0.036). Patients with
      diabetes mellitus had a significantly higher rate of screw loosening compared
      with those without diabetes (36.0% vs 15.8%, respectively; p = 0.024). Diabetic
      patients with well-controlled serum glucose (HbA1c <= 8.0%) had a significantly
      lower chance of screw loosening than those without well-controlled serum glucose
      (28.6% vs 71.4%, respectively; p = 0.021). Of the 25 patients with screw
      loosening, 22 cases (88%) were identified within 6.6 months of surgery; 18
      patients (72%) had the loosened screws in the inferior portion of the spinal
      construct, whereas 7 (28%) had screw loosening in the superior portion of the
      construct. The overall clinical outcomes at 3, 12, and 24 months, measured by VAS
      for back pain, VAS for leg pain, and ODI scores, were significantly improved
      after surgery compared with before surgery (all p < 0.05). There were no
      significant differences between the patients with and without screw loosening at
      all evaluation time points (all p > 0.05). All 25 patients with screw loosening
      were asymptomatic, and in 6 (24%) osseous integration was demonstrated on later
      follow-up. Also, there were 3 broken screws (2.38% in 126 patients or 0.46% in
      658 screws). To date, none of these loosened or broken screws have required
      revision surgery. CONCLUSIONS: Screw loosening in dynamic stabilization systems
      is not uncommon (4.7% screws in 19.8% patients). Patients of older age or those
      with diabetes have higher rates of screw loosening. Screw loosening can be
      asymptomatic and presents opportunity for osseous integration on later follow-up.
      Although adverse effects on clinical outcomes are rare, longer-term follow-up is
      required in cases in which screws become loose.

PMID- 21961873
TI  - Complications of spine surgery.

PMID- 21961874
TI  - Cortical deficits of emotional face processing in adults with ADHD: its relation
      to social cognition and executive function.
AB  - Although it has been shown that adults with attention-deficit hyperactivity
      disorder (ADHD) have impaired social cognition, no previous study has reported
      the brain correlates of face valence processing. This study looked for
      behavioral, neuropsychological, and electrophysiological markers of emotion
      processing for faces (N170) in adult ADHD compared to controls matched by age,
      gender, educational level, and handedness. We designed an event-related potential
      (ERP) study based on a dual valence task (DVT), in which faces and words were
      presented to test the effects of stimulus type (faces, words, or face-word
      stimuli) and valence (positive versus negative). Individual signatures of
      cognitive functioning in participants with ADHD and controls were assessed with a
      comprehensive neuropsychological evaluation, including executive functioning (EF)
      and theory of mind (ToM). Compared to controls, the adult ADHD group showed
      deficits in N170 emotion modulation for facial stimuli. These N170 impairments
      were observed in the absence of any deficit in facial structural processing,
      suggesting a specific ADHD impairment in early facial emotion modulation. The
      cortical current density mapping of N170 yielded a main neural source of N170 at
      posterior section of fusiform gyrus (maximum at left hemisphere for words and
      right hemisphere for faces and simultaneous stimuli). Neural generators of N170
      (fusiform gyrus) were reduced in ADHD. In those patients, N170 emotion processing
      was associated with performance on an emotional inference ToM task, and N170 from
      simultaneous stimuli was associated with EF, especially working memory. This is
      the first report to reveal an adult ADHD-specific impairment in the cortical
      modulation of emotion for faces and an association between N170 cortical measures
      and ToM and EF.

PMID- 21961875
TI  - Validation of Catalan version of BRIEF-P.
AB  - The BRIEF-P is one of the most used instruments to measure Executive Function
      (EF). This report is aimed at showing the psychometric properties of the Catalan
      version of it. To do this, a random cluster sampling was carried out in Osona
      (Catalonia), recruiting 417 teachers and 408 parents of children aged 3 to 6
      years. As with the original instrument, results show that reliability is
      excellent and that girls have a better EF than boys in the following areas:
      Working Memory, Plan/Organize, and Inhibit. Since in some areas Catalonia's
      preschool children show EF values slightly better than those of the reference
      sample, a new scale for using it in this population is provided.

PMID- 21961876
TI  - Tracking phospholipid profiling of muscle from Ctennopharyngodon idellus during
      storage by shotgun lipidomics.
AB  - This paper aims to study phospholipid (PL) profiling of muscle from 
      Ctenopharyngodon idellus  during room-temperature storage for 72 h by direct
      infusion electrospray ionization tandem mass spectrometry (ESI-MS/MS). Five
      classes of PLs, including phosphatidylcholine (PC), phosphatidylethanolamine
      (PE), phosphatidylinositol (PI), phosphatidylserine (PS), and sphingomyelin (SM),
      were analyzed. At least 110 molecular species of PLs were identified, including
      32 species of PC, 34 species of PE, 24 species of PS, 18 species of PI, and 2
      species of SM. The result showed that oxidation and hydrolysis are the two main
      causes for the deterioration of PLs in fish muscle during storage. Most content
      of PL molecular species increased and then decreased gradually. However, some
      special PE molecular species with former low abundance, such as PE 32:1, PE 34:2,
      and PE 34:1, emerged during the storage in quantity. It indicated that those PE
      molecular species may come from the microbe bred in the muscle. This phenomenon
      was found and discussed for the first time. The possible relevance between the
      emergence of these special PE molecular species and the freshness of the fish
      muscle during storage will be investigated in further studies.

PMID- 21961877
TI  - Diels-Alder via molecular recognition in a crystalline molecular flask.
AB  - In the pore of a porous coordination network, Diels-Alder reactants, a diene and
      a dienophile, are recognized by donor-acceptor and multiple H-bond interactions,
      respectively, and fixed at ideal positions for the reaction. Heating the crystals
      promoted the Diels-Alder reactions with enhanced reactivity and controlled
      regioselectivity as clearly monitored by in situ X-ray crystallography.

PMID- 21961882
TI  - ADHD in adolescents with borderline personality disorder.
AB  - BACKGROUND: The aims of this study were to assess the prevalence of a comorbid
      Attention Deficit Hyperactivity Disorder (ADHD) diagnosis in Borderline
      Personality Disorder (BPD), and its impact on the clinical presentation of BPD in
      adolescents, and to determine which type of impulsivity specifically
      characterizes adolescents with BPD-ADHD. METHODS: ADHD diagnoses were sought in a
      sample of 85 DSM-IV BPD adolescents drawn from the EURNET BPD. Axis-I and -II
      disorders were determined with the K-SADS-PL and the SIDP-IV, respectively.
      Impulsivity was assessed with the BIS-11. RESULTS: 11% (N = 9) of BPD
      participants had a current ADHD diagnosis. BPD-ADHD adolescents showed higher
      prevalence of Disruptive disorders (Chi2 = 9.09, p = 0.01) and a non-significant
      trend for a higher prevalence of other cluster B personality disorders (Chi2 =
      2.70, p = 0.08). Regression analyses revealed a significant association between
      Attentional/Cognitive impulsivity scores and ADHD (Wald Z = 6.69; p = 0.01;
      Exp(B) = 2.02, CI 95% 1.19-3.45). CONCLUSIONS: Comorbid ADHD influences the
      clinical presentation of adolescents with BPD and is associated with higher rates
      of disruptive disorders, with a trend towards a greater likelihood of cluster B
      personality disorders and with higher levels of impulsivity, especially of the
      attentional/cognitive type. A subgroup of BPD patients may exhibit
      developmentally driven impairments of the inhibitory system persisting since
      childhood. Specific interventions should be recommended for this subsample of BPD
      adolescents.

PMID- 21961883
TI  - Atrophy of the brachialis muscle after a displaced clavicle fracture in an
      Ironman triathlete: case report.
AB  - Clavicle fractures are frequent injuries in athletes and midshaft clavicle
      fractures in particular are well-known injuries in Ironman triathletes. In 2000,
      Auzou et al. described the mechanism leading to an isolated truncular paralysis
      of the musculocutaneous nerve after a shoulder trauma. It is well-known that
      nerve palsies can lead to an atrophy of the associated muscle if they persist for
      months or even longer. In this case report we describe a new case of an Ironman
      triathlete suffering from a persistent isolated atrophy of the brachialis muscle.
      The atrophy occurred following a displaced midshaft clavicle fracture acquiring
      while falling off his bike after hitting a duck during a competition.

PMID- 21961884
TI  - Interactive metagenomic visualization in a Web browser.
AB  - BACKGROUND: A critical output of metagenomic studies is the estimation of
      abundances of taxonomical or functional groups. The inherent uncertainty in
      assignments to these groups makes it important to consider both their
      hierarchical contexts and their prediction confidence. The current tools for
      visualizing metagenomic data, however, omit or distort quantitative hierarchical
      relationships and lack the facility for displaying secondary variables. RESULTS:
      Here we present Krona, a new visualization tool that allows intuitive exploration
      of relative abundances and confidences within the complex hierarchies of
      metagenomic classifications. Krona combines a variant of radial, space-filling
      displays with parametric coloring and interactive polar-coordinate zooming. The
      HTML5 and JavaScript implementation enables fully interactive charts that can be
      explored with any modern Web browser, without the need for installed software or
      plug-ins. This Web-based architecture also allows each chart to be an independent
      document, making them easy to share via e-mail or post to a standard Web server.
      To illustrate Krona's utility, we describe its application to various metagenomic
      data sets and its compatibility with popular metagenomic analysis tools.
      CONCLUSIONS: Krona is both a powerful metagenomic visualization tool and a
      demonstration of the potential of HTML5 for highly accessible bioinformatic
      visualizations. Its rich and interactive displays facilitate more informed
      interpretations of metagenomic analyses, while its implementation as a browser
      based application makes it extremely portable and easily adopted into existing
      analysis packages. Both the Krona rendering code and conversion tools are freely
      available under a BSD open-source license, and available from:
      http://krona.sourceforge.net.

PMID- 21961885
TI  - Immobilization of a human epidermal growth factor receptor 2 mimotope-derived
      synthetic peptide on Au and its potential application for detection of herceptin
      in human serum by quartz crystal microbalance.
AB  - Therapeutic antibodies are antigenically similar to human antibodies and are
      difficult to detect in assays of human serum samples without the use of the
      therapeutic antibody's complementary antigen. Herein for the first time, we
      established a platform to detect Herceptin in solutions by using a small (<2.2
      kDa), inexpensive, highly stable human epidermal growth factor receptor (HER2)
      mimotope-derived synthetic peptide immobilized on the surface of a Au quartz
      electrode. We used the HER2 mimotope as a substitute for the HER2 receptor
      protein in piezoimmunosensor or quartz crystal microbalance (QCM) assays to
      detect Herceptin in human serum. We demonstrated that assay sensitivity was
      dependent upon the amino acids used to tether and link the peptide to the sensor
      surface and the buffers used to carry out the assays. The detection limit of the
      piezoimmunosensor assay was 0.038 nM with a linear operating range of 0.038-0.859
      nM. Little nonspecific binding to other therapeutic antibodies (Avastin and
      Rituxan) was observed. Levels of Herceptin in serum samples obtained from treated
      patients, as ascertained using the synthetic peptide-based QCM assay, were
      typical for those treated with Herceptin. The findings of this study are
      significant in that low-cost synthetic peptides could be used in a QCM assay, in
      lieu of native or recombinant antigens or capture antibodies, to rapidly detect a
      therapeutic antibody in human serum. The results suggested that a synthetic
      peptide bearing a particular functional sequence could be applied for developing
      a new generation of affinity-based immunosensors to detect a broad range of
      clinical biomarkers.

PMID- 21961886
TI  - Selective N-alkylation of beta-alanine facilitates the synthesis of a poly(amino
      acid)-based theranostic nanoagent.
AB  - The development of functional amino acid-based polymeric materials is emerging as
      a platform to create biodegradable and nontoxic nanomaterials for medical and
      biotechnology applications. In particular, facile synthetic routes for these
      polymers and their corresponding polymeric nanomaterials would have a positive
      impact in the development of novel biomaterials and nanoparticles. However,
      progress has been hampered by the need to use complex protection-deprotection
      methods and toxic phase transfer catalysts. In this study, we report a facile,
      single-step approach for the synthesis of an N-alkylated amino acid as an AB-type
      functional monomer to generate a novel pseudo-poly(amino acid), without using the
      laborious multistep, protection-deprotection methods. This synthetic strategy is
      reproducible,  easy to scale up, and does not produce toxic byproducts. In
      addition, the synthesized amino acid-based polymer is different from conventional
      linear polymers as the butyl pendants enhance its solubility in common organic
      solvents and facilitate the creation of hydrophobic nanocavities for the
      effective encapsulation of hydrophobic cargos upon nanoparticle formation. Within
      the nanoparticles, we have encapsulated a hydrophobic DiI dye and a therapeutic
      drug, Taxol. In addition, we have conjugated folic acid as a folate receptor
      targeting ligand for the targeted delivery of the nanoparticles to cancer cells
      expressing the folate receptor. Cell cytotoxicity studies confirm the low
      toxicity of the polymeric nanoparticles, and drug-release experiments with the
      Taxol-encapsulated nanoparticles only exhibit cytotoxicity upon internalization
      into cancer cells expressing the folate receptor. Taken together, these results
      suggested that our synthetic strategy can be useful for the one-step synthesis of
      amino acid-based small molecules, biopolymers, and theranostic polymeric
      nanoagents for the targeted detection and treatment of cancer.

PMID- 21961887
TI  - A new rapidly absorbed paediatric paracetamol suspension. A six-way crossover
      pharmacokinetic study comparingthe rate and extent of paracetamol absorption from
      a new paracetamol suspension with two marketed paediatric formulations.
AB  - The objective of this study was to compare the rate and extent of paracetamol
      absorption from the new Paracetamol pediatric suspension (PPS) with two marketed
      paracetamol suspensions: Children's panadol (CP) and Panodil baby & infant (PBI).
      The study also assessed the effect on paracetamol absorption of light-calorie,
      low-fat food consumed 2 h before dosing. Twenty eight male adult volunteers
      received a single oral dose of 1000 mg of paracetamol from each of three
      treatments, in both fasted and fed states according to a randomized, single
      center, open-label, six-way crossover study design. PPS was bioequivalent to both
      CP and PBI for AUC(0-10 h), AUC(0-inf) and C(max) in both fasted and fed state.
      However, PPS had greater rate of paracetamol absorption and a faster speed of
      onset. T(max) for PPS was significantly shorter than for PBI in both fasted (p =
      0.0005) and fed state (p = 0.0001). Median T(max) for PPS was also 10 min shorter
      than CP in fasted state. Time to reach minimum effective concentration (MEC) for
      PPS was significantly shorter than CP and PBI. Early paracetamol exposure of PPS
      was significantly higher than that of the two existing paracetamol products. Food
      had a significant effect in the early exposure and onset of therapeutic level of
      paracetamol from PPS. AUC(0-30 min) was significantly higher and time to reach
      plasma paracetamol at MEC level was significantly shorter than in the fasted
      state.

PMID- 21961888
TI  - Systematic review of cost and cost-effectiveness of different TB-screening
      strategies.
AB  - BACKGROUND: Interferon-gamma release assays (IGRAs) for TB have the potential to
      replace the tuberculin skin test (TST) in screening for latent tuberculosis
      infection (LTBI). The higher per-test cost of IGRAs may be compensated for by
      lower post-screening costs (medical attention, chest x-rays and chemoprevention),
      given the higher specificity of the new tests as compared to that of the
      conventional TST. We conducted a systematic review of all publications that have
      addressed the cost or cost-effectiveness of IGRAs. The objective of this report
      was to undertake a structured review and critical appraisal of the methods used
      for the model-based cost-effectiveness analysis of TB screening programmes.
      METHODS: Using Medline and Embase, 75 publications that contained the terms
      "IGRA", "tuberculosis" and "cost" were identified. Of these, 13 were original
      studies on the costs or cost-effectiveness of IGRAs. RESULTS: The 13 relevant
      studies come from five low-to-medium TB-incidence countries. Five studies took
      only the costs of screening into consideration, while eight studies analysed the
      cost-effectiveness of different screening strategies. Screening was performed in
      high-risk groups: close contacts, immigrants from high-incidence countries and
      healthcare workers. Two studies used the T-SPOT.TB as an IGRA and the other
      studies used the QuantiFERON-TB Gold and/or Gold In-Tube test. All 13 studies
      observed a decrease in costs when the IGRAs were used. Six studies compared the
      use of an IGRA as a test to confirm a positive TST (TST/IGRA strategy) to the use
      of an IGRA-only strategy. In four of these studies, the two-step strategy and in
      two the IGRA-only strategy was more cost-effective. Assumptions about TST
      specificity and progression risk after a positive test had the greatest influence
      on determining which IGRA strategy was more cost-effective. CONCLUSION: The
      available studies on cost-effectiveness provide strong evidence in support of the
      use of IGRAs in screening risk groups such as HCWs, immigrants from high
      incidence countries and close contacts. So far, only two studies provide evidence
      that the IGRA-only screening strategy is more cost-effective.

PMID- 21961889
TI  - Simulation of solution phase electron transfer in a compact donor-acceptor dyad.
AB  - Charge separation (CS) and charge recombination (CR) rates in photosynthetic
      architectures are difficult to control, yet their ratio can make or break photon
      to-current conversion efficiencies. A rational design approach to the enhancement
      of CS over CR requires a mechanistic understanding of the underlying electron
      transfer (ET) process, including the role of the environment. Toward this goal,
      we introduce a QM/MM protocol for ET simulations and use it to characterize CR in
      the formanilide-anthraquinone dyad (FAAQ). Our simulations predict fast
      recombination of the charge-transfer excited state, in agreement with recent
      experiments. The computed electronic couplings show an electronic state
      dependence and are weaker in solution than in the gas phase. We explore the role
      of cis-trans isomerization on the CR kinetics, and we find strong correlation
      between the vertical energy gaps of the full simulations and a collective solvent
      polarization coordinate. Our approach relies on constrained density functional
      theory to obtain accurate diabatic electronic states on the fly for molecular
      dynamics simulations, while orientational and electronic polarization of the
      solvent is captured by a polarizable force field based on a Drude oscillator
      model. The method offers a unified approach to the characterization of driving
      forces, reorganization energies, electronic couplings, and nonlinear solvent
      effects in light-harvesting systems.

PMID- 21961890
TI  - Utility of total lymphocyte count as a surrogate marker for CD4 counts in HIV-1
      infected children in Kenya.
AB  - BACKGROUND: In resource-limited settings, such as Kenya, access to CD4 testing is
      limited. Therefore, evaluation of less expensive laboratory diagnostics is
      urgently needed to diagnose immuno-suppression in children. OBJECTIVES: To
      evaluate utility of total lymphocyte count (TLC) as surrogate marker for CD4
      count in HIV-infected children. METHODS: This was a hospital based retrospective
      study conducted in three HIV clinics in Kisumu and Nairobi in Kenya. TLC, CD4
      count and CD4 percent data were abstracted from hospital records of 487
      antiretroviral-naive HIV-infected children aged 1 month--12 years. RESULTS: TLC
      and CD4 count were positively correlated (r = 0.66, p < 0.001) with highest
      correlation seen in children with severe immuno-suppression (r = 0.72, p < 0.001)
      and children >59 months of age (r = 0.68, p < 0.001). Children were considered to
      have severe immuno-suppression if they met the following WHO set CD4 count
      thresholds: age below 12 months (CD4 counts < 1500 cells/mm(3)), age 12-35 months
      (CD4 count < 750 cells/mm(3)), age 36-59 months (CD4 count < 350 cells/mm(3), and
      age above 59 months (CD4 count < 200 cells/mm(3)). WHO recommended TLC threshold
      values for severe immuno-suppression of 4000, 3000, 2500 and 2000 cells/mm(3) for
      age categories <12, 12-35, 36-59 and >59 months had low sensitivity of 25%, 23%,
      33% and 62% respectively in predicting severe immuno-suppression using CD4 count
      as gold standard. Raising TLC thresholds to 7000, 6000, 4500 and 3000 cells/mm3
      for each of the stated age categories increased sensitivity to 71%, 64%, 56% and
      86%, with positive predictive values of 85%, 61%, 37%, 68% respectively but
      reduced specificity to 73%, 62%, 54% and 68% with negative predictive values of
      54%, 65%, 71% and 87% respectively. CONCLUSION: TLC is positively correlated with
      absolute CD4 count in children but current WHO age-specific thresholds had low
      sensitivity to identify severely immunosuppressed Kenyan children. Sensitivity
      and therefore utility of TLC to identify immuno-suppressed children may be
      improved by raising the TLC cut off levels across the various age categories.

PMID- 21961891
TI  - Facile method to synthesize magnetic iron oxides/TiO2 hybrid nanoparticles and
      their photodegradation application of methylene blue.
AB  - Many methods have been reported to improving the photocatalytic efficiency of
      organic pollutant and their reliable applications. In this work, we propose a
      facile pathway to prepare three different types of magnetic iron oxides/TiO2
      hybrid nanoparticles (NPs) by seed-mediated method. The hybrid NPs are composed
      of spindle, hollow, and ultrafine iron oxide NPs as seeds and 3
      aminopropyltriethyloxysilane as linker between the magnetic cores and TiO2
      layers, respectively. The composite structure and the presence of the iron oxide
      and titania phase have been confirmed by transmission electron microscopy, X-ray
      diffraction, and X-ray photoelectron spectra. The hybrid NPs show good magnetic
      response, which can get together under an external applied magnetic field and
      hence they should become promising magnetic recovery catalysts (MRCs).
      Photocatalytic ability examination of the magnetic hybrid NPs was carried out in
      methylene blue (MB) solutions illuminated under Hg light in a photochemical
      reactor. About 50% to 60% of MB was decomposed in 90 min in the presence of
      magnetic hybrid NPs. The synthesized magnetic hybrid NPs display high
      photocatalytic efficiency and will find recoverable potential applications in
      cleaning polluted water with the help of magnetic separation.

PMID- 21961892
TI  - Detecting latent tuberculosis infection during anti-tumor necrosis factor
      therapy.
AB  - OBJECTIVES: There is little information regarding the reliability of repeat
      tuberculin skin tests (TSTs) and interferon gamma release assays (IGRAs) in
      detecting latent tuberculosis infection (LTBI) in people on anti-tumour necrosis
      factor (TNF) medication. METHODS: We conducted a prospective, observational study
      of patients referred to the Saskatoon Tuberculosis (TB) Clinic prior to starting
      anti-TNF medication. A chest x-ray (CXR), 2-step TST and IGRA (QuantiFERON-TB
      Gold In-Tube Method) were performed at baseline. Those patients with a baseline
      TST >=10 mm and/or a positive IGRA were followed with a clinic visit, CXR, TST
      and IGRA at 3 and 6 months after starting anti-TNF medication. RESULTS: Of 106
      potential patients, 91 consented to participate. Twenty-six patients had a
      positive (>= 10 mm) TST or IGRA at baseline; twelve started and stayed on anti
      TNF medication through the 6-month follow-up and completed both planned follow-up
      visits. The baseline mean TST measurement for the 12 participants was 13.9 mm (SD
      11.4), increasing to a mean of 16.8 mm (SD 9.3) post-booster. At 3 months post
      anti-TNF initiation, there was an overall decrease in TST measurement (mean=10.0
      mm; SD 9.3; p=0.013), with measurements <5 mm in 3 of the 12 patients. By the 6
      month TST, a response recovery was observed with a mean TST measurement of 14.5
      mm (SD 7.7), with 11/12 >=5 mm. The IGRA was unchanged throughout the study
      period in all patients. The overall agreement between TST and IGRA was poor
      (kappa coefficient = 0.180, p=0.020). CONCLUSIONS: We demonstrated a transient
      but significant decrease in TST response in the first six months of anti-TNF
      therapy.

PMID- 21961893
TI  - Syntheses and structural characterizations of anionic borane-capped ammonia
      borane oligomers: evidence for ammonia borane H2 release via a base-promoted
      anionic dehydropolymerization mechanism.
AB  - Studies of the activating effect of Verkade's base, 2,8,9-triisobutyl-2,5,8,9
      tetraaza-1-phosphabicyclo[3.3.3]undecane (VB), on the rate and extent of H(2)
      release from ammonia borane (AB) have led to the syntheses and structural
      characterizations of three anionic aminoborane chain-growth products that provide
      direct support for anionic dehydropolymerization mechanistic steps in the initial
      stages of base-promoted AB H(2) release reactions. The salt
      VBH(+)[H(3)BNH(2)BH(2)NH(2)BH(3)](-) (1) containing a linear five-membered
      anionic aminoborane chain was produced in 74% yield via the room-temperature
      reaction of a 3:1 AB/VB mixture in fluorobenzene solvent, while the branched and
      linear-chain seven-membered anionic aminoborane oligomers
      VBH(+)[HB(NH(2)BH(3))(3)](-) (2a) and
      VBH(+)[H(3)BNH(2)BH(2)NH(2)BH(2)NH(2)BH(3)](-) (2b) were obtained from VB/AB
      reactions carried out at 50  degrees C for 5 days when the AB/VB ratio was
      increased to 4:1. X-ray crystal structure determinations confirmed that these
      compounds are the isoelectronic and isostructural analogues of the hydrocarbons n
      pentane, 3-ethylpentane, and n-heptane, respectively. The structural
      determinations also revealed significant interionic B-H...H-N dihydrogen-bonding
      interactions in these anions that could enhance dehydrocoupling chain-growth
      reactions. Such mechanistic pathways for AB H(2) release, involving the initial
      formation of the previously known [H(3)BNH(2)BH(3)](-) anion followed by
      sequential dehydrocoupling of B-H and H-N groups of growing borane-capped
      aminoborane anions with AB, are supported by the fact that 1 was observed to
      react with an additional AB equivalent to form 2a and 2b.

PMID- 21961894
TI  - Publication patterns of oral and poster presentations at the annual meetings of
      the Congress of Neurological Surgeons and the American Association of
      Neurological Surgeons.
AB  - OBJECT: National and international meetings, such as the Congress of Neurological
      Surgeons (CNS) and the American Association of Neurological Surgeons (AANS)
      meetings, provide a central location for the gathering and dissemination of
      research. The purpose of this study was to determine the publication rates of
      both oral and poster presentations at CNS and AANS meetings in peer-reviewed
      journals. METHODS: The authors reviewed all accepted abstracts, presented as
      either oral or poster presentations, at the CNS and AANS meetings from 2003 to
      2005. This information was then used to search PubMed to determine the rate of
      publication of the abstracts presented at the meetings. Abstracts were considered
      published if the data presented at the meeting was identical to that in the
      publication. RESULTS: The overall publication rate was 32.48% (1243 of 3827
      abstracts). On average, 41.28% of oral presentations and 29.03% of poster
      presentations were eventually published. Of those studies eventually published,
      98.71% were published within 5 years of presentation at the meeting. Published
      abstracts were published most frequently in the Journal of Neurosurgery and
      Neurosurgery. CONCLUSIONS: Approximately one-third of all presentations at the
      annual CNS and AANS meetings will be published in peer-reviewed, MEDLINE-indexed
      journals. These meetings are excellent forums for neurosurgical practitioners to
      be exposed to current research. Oral presentations have a significantly higher
      rate of eventual publication compared with poster presentations, reflecting their
      higher quality. The Journal of Neurosurgery and Neurosurgery have been the main
      outlets of neurosurgical research from these meetings.

PMID- 21961895
TI  - Quantitative analysis of cationic poly(vinyl alcohol) diffusion into the hairy
      structure of cellulose fiber pores: charge density effect.
AB  - The diffusion of charged polymers into the pores of cellulose fibers has not yet
      been fully understood due to the complexity of the interaction between polymers
      and fibers. In this paper, the diffusion of cationic-modified poly(vinyl alcohol)
      (CPVA) with tailored charge densities and a relatively high molecular weight into
      the pores of bleached aspen high-yield pulp (via a chemi-thermomechanical pulping
      process) was quantitatively investigated via an adsorption analysis, charge
      density analysis, and solute exclusion technique (SET). The results showed that
      the adsorption of the low-charged CPVA was substantially higher than that of the
      high-charged CPVA on fibers. The surface charge density analysis confirmed that
      approximately 17 mg/g of the high-charged CPVA adsorbed on the outer surface and
      on the macropores of fibers and the remaining (23 mg/g) diffused into the pores.
      The SET analysis confirmed that the pore size of fibers was more significantly
      reduced by applying the low-charged CPVA than the high-charged one. The
      influencing factors for the diffusion of CPVA into the large and small pores were
      related to the repulsion force developed between the adsorbed polymers and
      approaching polymers, entropy increase, and the polymer flexibility. The Brunauer
      Emmett-Teller surface area analysis showed an increase in the surface area of
      fibers upon CPVA adsorption. It was proposed that the diffused CPVA prevented
      complete fiber pore collapse during drying, which eventually increased the
      surface area of fibers.

PMID- 21961896
TI  - Accelerated rheumatoid nodulosis mimicking cystic subcutaneous infection.

PMID- 21961900
TI  - Plasmonic enhancements of photocatalytic activity of Pt/n-Si/Ag photodiodes using
      Au/Ag core/shell nanorods.
AB  - We report the plasmonic enhancement of the photocatalytic properties of Pt/n
      Si/Ag photodiode photocatalysts using Au/Ag core/shell nanorods. We show that
      Au/Ag core/shell nanorods can be synthesized with tunable plasmon resonance
      frequencies and then conjugated onto Pt/n-Si/Ag photodiodes using well-defined
      chemistry. Photocatalytic studies showed that the conjugation with Au/Ag
      core/shell nanorods can significantly enhance the photocatalytic activity by more
      than a factor of 3. Spectral dependence studies further revealed that the
      photocatalytic enhancement is strongly correlated with the plasmonic absorption
      spectra of the Au/Ag core/shell nanorods, unambiguously demonstrating the
      plasmonic enhancement effect.

PMID- 21961901
TI  - High molecular weight coffee melanoidins are inhibitors for matrix
      metalloproteases.
AB  - High molecular (above 10 kDa) melanoidins isolated from coffee beans of varying
      roasting degree were found to be efficient inhibitors for the zinc-containing
      matrix metalloproteases MMP-1, MMP-2, and MMP-9 with IC(50) values ranging
      between 0.2 and 1.1 mg/mL in vitro. The inhibitory potential increased with
      roasting degree. No or only slight inhibition of other zinc-containing peptidases
      closely related to MMPs, namely, Clostridium histolyticum collagenase and
      angiotensin converting enzyme, was found, indicating specific structural features
      of melanoidins to be responsible for the interaction with MMPs. A continuous
      increase on the apparent molecular weight of melanoidins as well as incorporation
      of phenolic substances into the melanoidin structure with progress of roasting
      was observed, concomitant with a significant increase in the carbon/nitrogen of
      the melanoidins. This suggests that the melanoidins are mainly formed by
      incorporation of carbohydrates and phenolic compounds onto a proteinaceous
      backbone. As MMP-1, MMP-2, and MMP-9 play a pivotal role in pathogenesis of
      colorectal cancer, studies on possible physiological effects of melanoidins are
      mandatory.

PMID- 21961902
TI  - Assessment of executive functioning in childhood epilepsy: the Tower of London
      and BRIEF.
AB  - Children and adolescents with epilepsy are known to demonstrate executive
      function dysfunction, including working memory deficits and planning deficits.
      Accordingly, assessing specific executive function skills is important when
      evaluating these individuals. The present investigation examined the utility of
      two measures of executive functions-the Tower of London and the Behavioral Rating
      Inventory of Executive Functioning (BRIEF)-in a pediatric epilepsy sample. Ninety
      clinically referred children and adolescents with seizures were included. Both
      the Tower of London and BRIEF identified executive dysfunction in these
      individuals, but only the Tower of London variables showed significant relations
      with epilepsy severity variables such as age of epilepsy onset, seizure
      frequency, number of antiepileptic medications, etc. Further, the Tower of London
      and BRIEF variables were uncorrelated. Results indicate that objective measures
      of executive function deficits are more closely related to epilepsy severity but
      may not predict observable deficits, as reported by parents. Comprehensive
      evaluation of such deficits, therefore, should include both objective measures as
      well as subjective ratings from caregivers.

PMID- 21961903
TI  - Partial anomalous pulmonary venous return and atrial septal defect in adult
      patients detected with 128-slice multidetector computed tomography.
AB  - The present series describes a group of adults with left-to-right shunts
      including partial anomalous pulmonary venous return (PAPVR) and/or an atrial
      septal defect (ASD) evaluated with ECG-gated 128-slice multidetector computed
      tomography (MDCT). PAPVR is defined as a left-to-right shunt where one or more,
      but not all, pulmonary veins drain into a systemic vein or the right atrium.
      PAPVR involving the right upper pulmonary vein can be associated with a sinus
      venosus ASD. The presence, course, number of anomalous veins and associated
      cardiovascular defects can be reliably observed by 128-slice MDCT angiography.

PMID- 21961904
TI  - Complementary characterization of buried nanolayers by quantitative X-ray
      fluorescence spectrometry under conventional and grazing incidence conditions.
AB  - The determination of the thickness and elemental composition is an important part
      of the characterization of nanolayered structures. For buried nanolayers, X-ray
      fluorescence spectrometry is a qualified method for the thickness determination
      whereas conventional electron emission based methods may reach their limits due
      to rather restricted information depths. The aim of the presented investigation
      was the comparison of reference-free X-ray fluorescence spectrometry under
      conventional and grazing incidence conditions offering complementary information
      with respect to quantification reliability, elemental sensitivity, and layer
      sequences. For this purpose, buried boron-carbon layers with nominal thicknesses
      of 1, 3, and 5 nm have been studied using monochromatized undulator radiation in
      the laboratory of the Physikalisch-Technische Bundesanstalt (PTB) at the
      synchrotron radiation facility BESSY II. The results for the two beam geometries
      are compared and show particulate good agreements, thus encouraging the
      complementary use of both methodologies.

PMID- 21961905
TI  - High-efficiency dye-sensitized solar cell with three-dimensional photoanode.
AB  - Herein, we present a straightforward bottom-up synthesis of a high electron
      mobility and highly light scattering macroporous photoanode for dye-sensitized
      solar cells. The dense three-dimensional Al/ZnO, SnO(2), or TiO(2) host
      integrates a conformal passivation thin film to reduce recombination and a large
      surface-area mesoporous anatase guest for high dye loading. This novel photoanode
      is designed to improve the charge extraction resulting in higher fill factor and
      photovoltage for DSCs. An increase in photovoltage of up to 110 mV over state-of
      the-art DSC is demonstrated.

PMID- 21961906
TI  - A pilot study of Aboriginal health promotion from an ecological perspective.
AB  - BACKGROUND: For health promotion to be effective in Aboriginal and Torres Strait
      Islander Communities, interventions (and their evaluation) need to work within a
      complex social environment and respect Indigenous knowledge, culture and social
      systems. At present, there is a lack of culturally appropriate evaluation methods
      available to practitioners that are capable of capturing this complexity. As an
      initial response to this problem, we used two non-invasive methods to evaluate a
      community-directed health promotion program, which aimed to improve nutrition and
      physical activity for members of the Aboriginal community of the Goulburn-Murray
      region of northern Victoria, Australia. The study addressed two main questions.
      First, for members of an Aboriginal sporting club, what changes were made to the
      nutrition environment in which they meet and how is this related to national
      guidelines for minimising the risk of chronic disease? Second, to what degree was
      the overall health promotion program aligned with an ecological model of health
      promotion that addresses physical, social and policy environments as well as
      individual knowledge and behaviour? METHODS: Rather than monitoring individual
      outcomes, evaluation methods reported on here assessed change in the nutrition
      environment (sports club food supply) as a facilitator of dietary change and the
      'ecological' nature of the overall program (that is, its complexity with respect
      to numbers of targets, settings and strategies). RESULTS: There were favourable
      changes towards the provision of a food supply consistent with Australian
      guidelines at the sports club. The ecological analysis indicated that the design
      and implementation of the program were consistent with an ecological model of
      health promotion. CONCLUSIONS: The evaluation was useful for assessing the impact
      of the program on the nutrition environment and for understanding the ecological
      nature of program activities.

PMID- 21961907
TI  - Encoding of social state information by neuronal activities in the macaque
      caudate nucleus.
AB  - Social animals adjust their behavior according to social relationships and
      momentary circumstances. Dominant-submissive relationships modulate, but do not
      completely determine, their competitive behaviors. For example, a submissive
      monkey's decision to retrieve food depends not only on the presence of dominant
      partners but also on their observed behavior. Thus, behavioral expression
      requires a dynamic evaluation of reward outcome and momentary social states. The
      neural mechanisms underlying this evaluation remain elusive. The caudate nucleus
      (CN) plays a pivotal role in representing reward expectation and translating it
      into action selection. To investigate whether their activities encode social
      state information, we recorded from CN neurons in monkeys while they performed a
      competitive food-grab task against a dominant competitor. We found two groups of
      CN neurons: one primarily responded to reward outcome, while the other primarily
      tracked the monkey's social state. These social state-dependent neurons showed
      greater activity when the monkeys freely retrieved food without active challenges
      from the competitor and reduced activity when the monkeys were in a submissive
      state due to the competitor's active behavior. These results indicate that
      different neuronal activities in the CN encode social state information and
      reward-related information, which may contribute to adjusting competitive
      behavior in dynamic social contexts.

PMID- 21961908
TI  - Evolutionary relationships of the old world fruit bats (Chiroptera,
      Pteropodidae): another star phylogeny?
AB  - BACKGROUND: The family Pteropodidae comprises bats commonly known as megabats or
      Old World fruit bats. Molecular phylogenetic studies of pteropodids have provided
      considerable insight into intrafamilial relationships, but these studies have
      included only a fraction of the extant diversity (a maximum of 26 out of the 46
      currently recognized genera) and have failed to resolve deep relationships among
      internal clades. Here we readdress the systematics of pteropodids by applying a
      strategy to try to resolve ancient relationships within Pteropodidae, while
      providing further insight into subgroup membership, by 1) increasing the
      taxonomic sample to 42 genera; 2) increasing the number of characters (to >8,000
      bp) and nuclear genomic representation; 3) minimizing missing data; 4)
      controlling for sequence bias; and 5) using appropriate data partitioning and
      models of sequence evolution. RESULTS: Our analyses recovered six principal
      clades and one additional independent lineage (consisting of a single genus)
      within Pteropodidae. Reciprocal monophyly of these groups was highly supported
      and generally congruent among the different methods and datasets used. Likewise,
      most relationships within these principal clades were well resolved and
      statistically supported. Relationships among the 7 principal groups, however,
      were poorly supported in all analyses. This result could not be explained by any
      detectable systematic bias in the data or incongruence among loci. The SOWH test
      confirmed that basal branches' lengths were not different from zero, which points
      to closely-spaced cladogenesis as the most likely explanation for the poor
      resolution of the deep pteropodid relationships. Simulations suggest that an
      increase in the amount of sequence data is likely to solve this problem.
      CONCLUSIONS: The phylogenetic hypothesis generated here provides a robust
      framework for a revised cladistic classification of Pteropodidae into subfamilies
      and tribes and will greatly contribute to the understanding of character
      evolution and biogeography of pteropodids. The inability of our data to resolve
      the deepest relationships of the major pteropodid lineages suggests an explosive
      diversification soon after origin of the crown pteropodids. Several
      characteristics of pteropodids are consistent with this conclusion, including
      high species diversity, great morphological diversity, and presence of key
      innovations in relation to their sister group.

PMID- 21961909
TI  - Preparation and physicochemical evaluation of a new tacrolimus tablet formulation
      for sublingual administration.
AB  - The aim of this study was to develop a new fast-disintegrating tablet formulation
      containing 1 mg tacrolimus for sublingual application. First, solid dispersions
      containing tacrolimus (2.5%, 5% and 10% w/w) incorporated in Ac-Di-Sol((r)) and
      carriers (inulin 1.8 kDa and 4 kDa, and polyvinylpyrrolidone (PVP) K30) were
      prepared by freeze drying. Subsequently, a tablet formulation composed of a
      mixture of the solid dispersions, Ac-Di-Sol((r)), mannitol, Avicel((r)) PH-101
      and sodium stearyl fumarate was optimized concerning drug load in the solid
      dispersions and the type of carrier. Tablet weight was kept constant at 75 mg by
      adjusting the amount of Avicel((r)) PH-101. Differential scanning calorimetry
      (DSC) and X-ray powder diffraction (XRPD) results indicated the absence of the
      drug in the crystalline state, which was confirmed by the scanning electron
      microscopy (SEM). These results suggest that tacrolimus incorporated in all of
      the solid dispersions was fully amorphous. Dissolution of the tablets containing
      solid dispersions with a low drug load highly depends on the type of carrier and
      increased in the order: PVP K30 < inulin 4 kDa < inulin 1.8 kDa. Solid
      dispersions with a drug load of 10% w/w incorporated in the carriers yielded
      optimal formulations. In addition, the physicochemical characteristics and the
      dissolution behavior of the tablet formulation containing inulin 1.8 kDa-based
      solid dispersions with a drug load of 10% w/w did not change after storage at 20
      degrees C/45%RH for 6 months indicating excellent storage stability.

PMID- 21961910
TI  - Controlling terahertz radiation with nanoscale metal barriers embedded in nano
      slot antennas.
AB  - Nanoscale metallic barriers embedded in terahertz (THz) slot antennas are shown
      to provide unprecedented control of the transition state arising at the crossover
      between the full- and half-wavelength resonant modes of such antennas. We
      demonstrate strong near-field coupling between two paired THz slot antennas
      separated by a 5 nm wide nanobarrier, almost fully inducing the shift to the
      resonance of the double-length slot antenna. This increases by a factor of 50 the
      length-scale needed to observe similar coupling strengths in conventional air-gap
      antennas (around 0.1 nm), making the transition state readily accessible to
      experiment. Our measurements are in good agreement with a quantitative
      theoretical modeling, which also provides a simple physical picture of our
      observations.

PMID- 21961911
TI  - Barriers to conducting clinical research in reproductive medicine around the
      world.
AB  - We asked seven senior and accomplished investigators from around the world to
      share their experiences conducting research in reproductive medicine.

PMID- 21961912
TI  - Barriers to conducting clinical research in reproductive medicine: Latin America.
AB  - Societies in Latin America are not scientifically driven and therefore, the
      allocation of human and economic resources to research is meager, as a reflection
      of this as well as other cultural and economic realities.

PMID- 21961913
TI  - Barriers to conducting clinical research in reproductive medicine: Egypt.
AB  - There are many barriers to scientific research in Egypt, including lack of
      funding, lack of a scientific atmosphere, and "brain drain" of scientists who
      produce high quality research.

PMID- 21961914
TI  - Barriers to conducting clinical research in reproductive medicine: Greece.
AB  - In Greece, procedures for obtaining funding and/or state approval for a research
      project are lengthy, hinder collaboration between centers, and may render
      projects outdated.

PMID- 21961915
TI  - Barriers to conducting clinical research in reproductive medicine: India.
AB  - Research in India is evolving at a rapid pace. Ergo, we need faster approval
      processes and review timelines. Improvement in the quality of institutional
      review boards would also contribute to good research practices. Clinical research
      should be included as a part of the undergraduate medical and pharmacy
      curriculum, and leading hospitals and practitioners should openly endorse
      research.

PMID- 21961916
TI  - Barriers to conducting clinical research in reproductive medicine: China.
AB  - In China, our research personnel and projects are mainly funded by the central
      government, provincial government, and nongovernmental foundations. Occasionally,
      we do some multicenter clinical research under the solicitation of pharmaceutical
      companies.

PMID- 21961917
TI  - Barriers to conducting clinical research in reproductive medicine: Australia and
      the United Kingdom.
AB  - There are several major barriers to research in reproductive medicine in the
      United Kingdom and Australia. In Australia these mainly reflect income disparity
      between research and private practice whereas in United Kingdom they reflect the
      consequences of the economic downturn.

PMID- 21961918
TI  - Barriers to conducting clinical research in reproductive medicine: United States
      of America.
AB  - A decrease in National Institute of Health funding and an increase regulations
      are significant barriers in conducting research in the United States of America.

PMID- 21961919
TI  - Early menopause in mothers of children with Down syndrome?
AB  - OBJECTIVE: To investigate whether having a Down syndrome pregnancy at a
      relatively young age is associated with lower ovarian reserve as reflected by
      lower antimullerian hormone (AMH) levels and the occurrence of earlier menopause.
      DESIGN: Retrospective, case control study. SETTING: Not applicable. PATIENT(S):
      Two hundred twenty mothers (118 trisomy cases, 102 controls). INTERVENTION(S):
      Questionnaire and serum AMH measurement. MAIN OUTCOME MEASURE(S): Serum AMH
      levels and menopause, defined as not having a menstrual cycle for at least 1
      year. RESULT(S): The participant response rate was 93%. After applying the
      exclusion criteria, 144 women were evaluable (73 trisomy cases, and 71 controls).
      The baseline characteristics of the women were not statistically significantly
      different. More women with a Down syndrome pregnancy had an AMH level below 0.5
      MUg/L, a difference that was statistically significant. Eleven women (15.1%) in
      the Down syndrome group had reached menopause compared with 9 (12.7%) of the
      controls. CONCLUSION(S): Women who have had a Down syndrome pregnancy at a
      younger age show signs of limited ovarian reserve, as evidenced by their
      frequently having lower AMH levels. The study has found no obvious signs of early
      menopause thus far. Whether their age at menopause is within the normal range
      remains to be determined.

PMID- 21961920
TI  - Differential susceptibility of a few members of the nasuta-albomicans complex of
      Drosophila to paraquat-induced lethality and oxidative stress.
AB  - The evolution of karyotypically stabilized short-lived (SL) and long-lived (LL)
      cytoraces in the laboratory have been established and validated through our
      previous lifespan studies. In the present investigation, we examined the possible
      reason(s) for the differential longevity among selected members of SL and LL
      cytoraces, employing the well known paraquat (PQ) resistance bioassay. Exposure
      of these races to varying concentrations of PQ revealed relatively higher
      resistance among LL cytoraces than SL cytoraces, as evident by the lower
      incidence of mortality. Biochemical analysis for endogenous markers of oxidative
      stress revealed that LL-2 cytorace exhibited lower reactive oxygen species (ROS)
      and lipid peroxidation (LPO) levels, higher activity levels of superoxide
      dismutase (SOD), and coupled with higher levels of reduced glutathione (GSH)
      compared with the levels found in SL-2 cytorace. These findings suggest that the
      higher susceptibility of SL cytoraces to PQ challenge may be, at least in part,
      related to the higher endogenous levels of oxidative stress markers. Although the
      precise mechanisms responsible for the longer longevity among LL cytoraces of the
      nasuta-albomicans complex of Drosophila merits further investigation, our data
      suggest that the relatively longer lifespan may be related to the status of
      endogenous markers that renders them more resistant towards oxidative-stress
      mediated lethality, as evident in the PQ assay.

PMID- 21961921
TI  - A novel gas ionization sensor using Pd nanoparticle-capped ZnO.
AB  - A novel gas ionization sensor using Pd nanoparticle-capped ZnO (Pd/ZnO) nanorods
      as the anode is proposed. The Pd/ZnO nanorod-based sensors, compared with the
      bare ZnO nanorod, show lower breakdown voltage for the detected gases with good
      sensitivity and selectivity. Moreover, the sensors exhibit stable performance
      after more than 200 tests for both inert and active gases. The simple, low-cost,
      Pd/ZnO nanorod-based field-ionization gas sensors presented in this study have
      potential applications in the field of gas sensor devices.

PMID- 21961922
TI  - Granulomatous hepatitis, choroiditis and aortoduodenal fistula complicating
      intravesical Bacillus Calmette-Guerin therapy: Case report.
AB  - BACKGROUND: Intravesical instillation of Bacillus Calmette-Guerin (BCG) is the
      treatment of choice for superficial bladder carcinoma. Complications of BCG
      therapy include local infections and disseminated BCG infection with multiple
      endorgan complications. CASE PRESENTATION: We report a case of disseminated, post
      treatment BCG infection that initially presented with granulomatous hepatitis and
      choroiditis. After successful anti-mycobacterial therapy and resolution of the
      hepatic and ocular abnormalities, the patient developed an acute upper
      gastrointestinal hemorrhage from an aortoduodenal fistula that required emergency
      surgery. The resection specimen revealed multifocal, non-caseating granulomas,
      indicating mycobacterial involvement. CONCLUSIONS: This case highlights the
      varied end organ complications of disseminated BCG infection, and the need for
      vigilance even in immuno-competent patients with a history of intravesical BCG
      treatment.

PMID- 21961923
TI  - A computer Time Trade-Off: a feasible and reliable alternative for the interview
      Time Trade-Off in rheumatoid arthritis.
AB  - OBJECTIVES: The Time Trade-Off (TTO) is an instrument used for valuing health
      related quality of life. This study evaluated the test-retest reliability of a
      computer TTO in rheumatoid arthritis (RA), and compared the computer with the
      interview TTO regarding feasibility and agreement. METHODS: In study 1 using a
      cross-over design, thirty patients completed both TTOs. In study 2, twenty-nine
      other patients completed the computer TTO twice to examine test-retest
      reliability. Feasibility was measured by assessing actual and perceived time
      duration and general experience of the patient. Agreement between utility scores
      of both TTOs was measured by Bland-Altman analysis. RESULTS: Both TTOs were
      feasible. The computer TTO showed high test-retest reliability (ICC = 0.88).
      Bland-Altman analysis showed a small mean difference (0.06, SD = 0.14, effect
      size=0.30) between both TTOs. Limits of agreement were wide (-0.22 to 0.34).
      Differences between interview and computer TTO utilities did not vary over the
      range of scores. CONCLUSIONS: The computer TTO was feasible and reliable, but did
      not provide similar results as the interview TTO. However, no systematic biases
      in the differences were found over the range of scores.

PMID- 21961924
TI  - Increasing treatment of ruptured cerebral aneurysms at high-volume centers in the
      United States.
AB  - OBJECT: Evidence of better outcomes in patients with aneurysmal subarachnoid
      hemorrhage treated at higher-volume centers might be expected to result in more
      of these patients being referred to such centers. The authors evaluated the US
      National Inpatient Sample for the years 2001 to 2008 for trends in patient
      admissions for the treatment of ruptured aneurysms at high- and low-volume
      centers. METHODS: The authors determined the number of ruptured aneurysms treated
      with clipping or coiling annually at low-volume (<= 20 patients/year) and high
      volume (> 20 patients/year) centers and also counted the number of high- and low
      volume centers performing each treatment. Hospitalizations for clipping or
      coiling ruptured aneurysms were identified by cross-matching International
      Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes
      for the diagnosis of a ruptured aneurysm (ICD-9-CM 430) with procedure codes for
      clipping (ICD-9-CM 39.51) or coiling (ICD-9-CM 39.52, 39.79, or 39.72) cerebral
      aneurysms. RESULTS: In 2001, 31% (435 of 1392) of the patients who underwent
      clipping and 0% (0 of 122 patients) of those who underwent coiling did so at high
      volume centers, whereas in 2008 these numbers increased to 62% (627 of 1016) and
      68% (917 of 1351) of patients, respectively. For clipping procedures, the number
      of low-volume centers significantly declined from 177 in 2001 to 85 in 2008,
      whereas the number of high-volume centers remained constant at 13-15. For coiling
      procedures, the number of low-volume centers decreased from 62 in 2001 to 54 in
      2008, whereas the number of high-volume centers substantially increased from 0 in
      2001 to 16 in 2005 and remained constant thereafter. CONCLUSIONS: The treatment
      of ruptured cerebral aneurysms increasingly occurs at high-volume centers in the
      US. This trend is favorable given that better outcomes are associated with the
      treatment of these lesions at high-volume centers.

PMID- 21961925
TI  - A systematic exploration of differences in contextual factors related to
      implementing the MOVE! weight management program in VA: a mixed methods study.
AB  - BACKGROUND: In January 2006, Veterans Affairs (VA) disseminated the MOVE!(r)
      Weight Management Program to VA medical centers to address the high prevalence of
      overweight/obesity. In its second year, MOVE! implementation varied widely across
      facilities. The objective of this study was to understand contextual factors that
      facilitated or impeded implementation of MOVE! in VA medical centers in the
      second year after its dissemination. METHODS: We used an embedded mixed methods
      cross-sectional study design. Qualitative and quantitative data were collected
      simultaneously with the primary purpose to explore contextual factors most likely
      to influence MOVE! implementation effectiveness at five purposively selected
      facilities. Facilities were selected to maximize variation with respect to
      participation in MOVE! by candidate Veterans. Semi-structured phone interviews
      were conducted with 24 staff across the five facilities. Quantitative responses
      were elicited followed by open-ended questions. The quantitative measures were
      adapted from a published implementation model. Qualitative analysis was conducted
      using rigorous content analysis methods. RESULTS: Qualitative and quantitative
      data converged to strengthen findings that point to several recommendations.
      Management support can help increase visibility of the program, commit needed
      resources, and communicate the importance of implementation efforts. Establishing
      a receptive implementation climate can be accomplished by emphasizing the
      important role that weight management may have in reducing incidence and severity
      of obesity-related chronic conditions. Coalescing highly functioning multi
      disciplinary teams was an essential step for more effective implementation of
      MOVE!. In some situations, local champions can overcome challenging barriers in
      facilities that lack sufficient management support. CONCLUSIONS: Key
      organizational factors at local VA medical centers were strongly associated with
      MOVE! implementation. Results pointed to recommendations that can help accelerate
      large-scale dissemination of complex weight management programs.

PMID- 21961929
TI  - Postprandial glycemia, insulinemia, and satiety responses in healthy subjects
      after whole grain rye bread made from different rye varieties. 1.
AB  - Rye products typically induce low insulin responses and appear to facilitate
      glucose regulation. The objective of this study was to investigate differences in
      postprandial glucose, insulin, and satiety responses between breads made from
      five rye varieties. Breads made from whole grain rye (Amilo, Rekrut, Dankowski
      Zlote, Nikita, and Haute Loire Pop) or a white wheat bread (WWB) were tested in a
      randomized cross-over design in 14 healthy subjects (50 g available starch).
      Metabolic responses were also related to the composition of dietary fiber and
      bioactive compounds in the breads and to the rate of in vitro starch hydrolysis.
      The Amilo and Rekrut rye breads induced significantly lower insulin indices (II)
      than WWB. Low early postprandial glucose and insulin responses (tAUC 0-60 min)
      were related to higher amounts of caffeic, ferulic, sinapic, and vanillic acids
      in the rye breads, indicating that the phenolic acids in rye may influence
      glycemic regulation. All rye breads induced significantly higher subjective
      feelings of fullness compared to WWB. A low II was related to a higher feeling of
      fullness and a lower desire to eat in the late postprandial phase (180 min). The
      data indicate that some rye varieties may be more insulin-saving than others,
      possibly due to differences in dietary fiber, rate of starch hydrolysis, and
      bioactive components such as phenolic acids.

PMID- 21961930
TI  - Molecular identification of Lodoicea maldivica (coco de mer) seeds.
AB  - BACKGROUND: The edible endosperm of Lodoicea maldivica with the common name of
      coco de mer is used in Chinese medicine for treating cough. Native to Seychelles,
      Lodoicea maldivica seeds have commanded high prices for centuries due to its
      scarcity. This study aims to develop a molecular identification method for the
      authentication of Lodoicea maldivica seeds. METHODS: DNA was extracted from the
      sample. Two polymerase chain reaction (PCR) systems were developed to amplify a
      region of the chloroplast DNA and the nuclear phosphoribulokinase (PRK) region
      specific to Lodoicea maldivica respectively. DNA sequence of a sample was
      determined and compared with that of the Lodoicea maldivica reference material.
      RESULTS: The PRK gene of Lodoicea maldivica was successfully amplified and
      sequenced for identification. CONCLUSION: A new molecular method for the
      identification of Lodoicea maldivica seeds in fresh, frozen or dried forms was
      developed.

PMID- 21961931
TI  - Spin specific electron conduction through DNA oligomers.
AB  - Spin-based properties, applications, and devices are commonly related to magnetic
      effects and to magnetic materials. Most of the development in spintronics is
      currently based on inorganic materials. Despite the fact that the
      magnetoresistance effect has been observed in organic materials, until now spin
      selectivity of organic based spintronics devices originated from an inorganic
      ferromagnetic electrode and was not determined by the organic molecules
      themselves. Here we show that conduction through double-stranded DNA oligomers is
      spin selective, demonstrating a true organic spin filter. The selectivity exceeds
      that of any known system at room temperature. The spin dependent resistivity
      indicates that the effect cannot result solely from the atomic spin-orbit
      coupling and must relate to a special property resulting from the chirality
      symmetry. The results may reflect on the importance of spin in determining
      electron transfer rates through biological systems.

PMID- 21961932
TI  - Improving STD testing behavior among high-risk young adults by offering STD
      testing at a vocational school.
AB  - BACKGROUND: Chlamydia trachomatis infection (CT) is the most prevalent bacterial
      STD. Sexually active adolescents and young adults are the main risk group for CT.
      However, STD testing rates in this group are low since exposed individuals may
      not feel at risk, owing-at least in part-to the infection's largely asymptomatic
      nature. Designing new testing environments that are more appealing to young
      people who are most at risk of acquiring chlamydia can be an important strategy
      to improve overall testing rates. Here we evaluate the effect of a school-based
      sexual health program conducted among vocational school students, aiming to
      obtain better access for counseling and enhance students' STD testing behavior.
      METHODS: Adolescents (median age 19 years) attending a large vocational school
      were provided with sexual health education. Students filled in a questionnaire
      measuring CT risk and were offered STD testing. Using univariate and multivariate
      analysis, we assessed differences between men and women in STD-related risk
      behavior, sexual problems, CT testing behavior and determinants of CT testing
      behavior. RESULTS: Of 345 participants, 70% were female. Of the 287 sexually
      active students, 75% were at high risk for CT; one third of women reported sexual
      problems. Of sexually active participants, 61% provided a self-administered
      specimen for STD testing. Independent determinants for testing included STD
      related symptoms and no condom use. All CT diagnoses were in the high-CT-risk
      group. In the high-risk group, STD testing showed an increased uptake, from 27%
      (previous self-reported test) to 65% (current test). CT prevalence was 5.7%.
      CONCLUSIONS: Vocational school students are a target population for versatile
      sexual health prevention. When provided with CT testing facilities and education,
      self selection mechanisms seemed to increase CT testing rate dramatically in this
      high-CT-risk population expressing sexual problems. Considering the relative ease
      of testing and treating large numbers of young adults, offering tests at a
      vocational school is feasible in reaching adolescents for STD screening. Although
      cost-effectiveness remains an issue counseling is effective in increasing test
      rates.

PMID- 21961934
TI  - Quantitative analysis of adsorbed proteins by X-ray photoelectron spectroscopy.
AB  - Protein adsorption at solid surfaces is central to many phenomena of medical and
      technological interest. The determination of the amount of protein attached to
      the surface is a critical measurement performed by using a wide range of methods.
      X-ray photoelectron spectroscopy (XPS) is able to provide a straightforward
      quantitative analysis of the amount of protein adsorbed as an overlayer on a
      material surface. While XPS is commonly employed to assess qualitatively the
      amount of adsorbed protein, this is usually expressed in terms of the elemental
      fraction (or at. %) of nitrogen calculated using an assumption of depth
      homogeneity despite the fact that this does not linearly scale with the amount of
      protein. In this paper, we have shown that thicknesses derived from XPS data
      linearly correlated with spectroscopic ellipsometry data on the same samples with
      a scatter of 10%. A straightforward equation to convert the concentration of
      nitrogen from XPS into an equivalent thickness of a protein film is presented. We
      highlight some discrepancies in the absolute thicknesses determined by XPS and
      ellipsometry on dried films and quartz crystal microbalance on wet films, which
      appear likely to result from the inclusion of a contribution from water in the
      latter two techniques.

PMID- 21961933
TI  - Sex in the PAC: a hidden affair in dark septate endophytes?
AB  - BACKGROUND: Fungi are asexually and sexually reproducing organisms that can
      combine the evolutionary advantages of the two reproductive modes. However, for
      many fungi the sexual cycle has never been observed in the field or in vitro and
      it remains unclear whether sexual reproduction is absent or cryptic.
      Nevertheless, there are indirect approaches to assess the occurrence of sex in a
      species, such as population studies, expression analysis of genes involved in
      mating processes and analysis of their selective constraints. The members of the
      Phialocephala fortinii s. l. - Acephala applanata species complex (PAC) are
      ascomycetes and the predominant dark septate endophytes that colonize woody plant
      roots. Despite their abundance in many ecosystems of the northern hemisphere, no
      sexual state has been identified to date and little is known about their
      reproductive biology, and how it shaped their evolutionary history and
      contributes to their ecological role in forest ecosystems. We therefore aimed at
      assessing the importance of sexual reproduction by indirect approaches that
      included molecular analyses of the mating type (MAT) genes involved in
      reproductive processes. RESULTS: The study included 19 PAC species and > 3, 000
      strains that represented populations from different hosts, continents and
      ecosystems. Whereas A. applanata had a homothallic (self-fertile) MAT locus
      structure, all other species were structurally heterothallic (self-sterile).
      Compatible mating types were observed to co-occur more frequently than expected
      by chance. Moreover, in > 80% of the populations a 1:1 mating type ratio and
      gametic equilibrium were found. MAT genes were shown to evolve under strong
      purifying selection. CONCLUSIONS: The signature of sex was found in worldwide
      populations of PAC species and functionality of MAT genes is likely preserved by
      purifying selection. We hypothesize that cryptic sex regularely occurs in the PAC
      and that further field studies and in vitro crosses will lead to the discovery of
      the sexual state. Although structurally heterothallic species prevail, it cannot
      be excluded that homothallism represents the ancestral breeding system in the
      PAC.

PMID- 21961935
TI  - Analysis of stability of nanotube dispersions using surface tension isotherms.
AB  - In this paper, we present the analyses of surface tension of surfactant
      stabilized dispersions of carbon nanotubes. This method allows one to study
      interactions of carbon nanotubes with surfactants at different levels of nanotube
      loading when optical methods fall short in quantifying the level of nanotube
      separation. Sodium dodecyl sulfate was used as a stabilizing agent to uniformly
      disperse single-walled carbon nanotubes in an aqueous media. We show that surface
      tension is very sensitive to small changes of nanotube and surfactant
      concentrations. The experimental data suggest that, at moderate concentrations,
      surfactant displaces carbon nanotubes from the air-water interface and the
      nanotubes are mostly moved into the bulk of the liquid. By analyzing the surface
      tension as a function of surfactant concentration, we obtained the dependence of
      critical micelle concentration on nanotube loading. We then constructed the
      adsorption isotherm for dodecyl sulfate on carbon nanotubes and bundles of carbon
      nanotubes. The results of these experiments enabled us to extend the phase
      diagram of the produced dispersions to a broader range of surfactant and nanotube
      concentrations.

PMID- 21961936
TI  - Selective deficit in spatial location memory in extremely low birth weight
      children at age six: the PETIT study.
AB  - Spatial location memory has rarely been assessed in young children due to a
      scarcity of developmentally appropriate tests. This study sought to compare
      nonverbal learning and recall in children born extremely low birth weight (ELBW;
      <1000 g) and less than 33 gestational weeks (GW) with term-born children at early
      school age using a recently developed and adapted test. We administered a
      modification of the Hopkins Board to 210 children at age six; 84 born ELBW (35
      born < 26 GW; 49 born 26-33 GW) and 126 term-born. Six measures were obtained:
      naming, trials-to-criterion, errors-to-criterion, delayed item recall, delayed
      location recall, and percent retention. After age correction, ELBW children had
      worse general cognition, item naming, delayed item recall, delayed location
      recall, and percent retention than term-born children. Delayed item recall and
      percent retention performances of ELBW children remained worse after correction
      for general cognition. ELBW groups (< 26 GW and 26-33 GW) groups performed worse
      than term-born children in naming and delayed item recall with chronological age
      as covariate. Those born before 26 GW, but not 26-33 GW, performed worse than
      term-born children in delayed location recall and percent retention. Differences
      remained significant after controlling for gender, maternal education, and
      delivery type. All three groups' performance declined from final learning trial
      to delayed location recall, with a decline greater for less than 26 GW than term
      born children. Extreme prematurity (< 26 GW) and ELBW are significant risk
      factors for spatial location memory deficit. The modified Hopkins Board
      discriminated high-risk preterm and term-born children at early school age and
      appears to be a useful test to measure this rarely studied cognitive capacity. 

PMID- 21961937
TI  - Sugar coated ceramic nanocarriers for the oral delivery of hydrophobic drugs:
      formulation, optimization and evaluation.
AB  - In order to enhance the delivery of poorly-soluble drugs, we have explored
      aquasomes (three-layered, ceramic core based, oligosaccharide coated
      nanoparticles) as potential carriers for the delivery of model hydrophobic drug
      piroxicam (log P = 3.1). Ceramic nanoparticles were prepared using two
      techniques; namely, co-precipitation by refluxing and co-precipitation by
      sonication. Core preparation was finally done using sonication approach; based on
      the higher % yield (42.4 +/- 0.4%) and shorter duration (1 day) compared to the
      reflux method (27.4 +/- 2.05%, 6 days). Lactose loading onto ceramic core was
      achieved using adsorption. Colorimetric analysis of lactose coating was done
      using Anthrone method. Optimization of process variables namely, incubation time
      and core to coat ratio (for sugar loading) was carried out. Optimum time of
      incubation was 3 h and the core to coat ratio was 4:1. The drug loading was
      achieved by incubating the sugar loaded cores in different concentrations of
      piroxicam solution and it was found that 1.5% w/v piroxicam was optimal.
      Structural characterization using Fourier-Transform Infra Red Spectroscopy (FTIR)
      confirmed the presence of sugar coating onto the core. Morphological evaluation
      using transmission electron microscopy (TEM) revealed spherical nanoparticles
      (size 56.56 +/- 5.93 nm for lactose coated core and 184.75 +/- 13.78 nm for
      piroxicam loaded aquasomes) confirming the nanometric dimensions.

PMID- 21961938
TI  - Understanding the effect of polylysine architecture on DNA binding using
      molecular dynamics simulations.
AB  - Polycations with varying chemistries and architectures have been synthesized and
      used in DNA transfection. In this paper we connect poly-L-lysine (PLL)
      architecture to DNA-binding strength, and in turn transfection efficiency, since
      experiments have shown that graft-type oligolysine architectures [e.g.,
      poly(cyclooctene-g-oligolysine)] exhibit higher transfection efficiency than
      linear PLL. We use atomistic molecular dynamics simulations to study structural
      and thermodynamic effects of polycation-DNA binding for linear PLL and grafted
      oligolysines of varying graft lengths. Structurally, linear PLL binds in a
      concerted manner, while each oligolysine graft binds independently of its
      neighbors in the grafted architecture. Additionally, the presence of a
      hydrophobic backbone in the grafted architecture weakens binding to DNA compared
      to linear PLL. The binding free energy varies nonmonotonically with the graft
      length primarily due to entropic contributions. The binding free energy
      normalized to the number of bound amines is similar between the grafted and
      linear architectures at the largest (Poly5) and smallest (Poly2) graft length and
      stronger than the intermediate graft lengths (Poly3 and Poly4). These trends
      agree with experimental results that show higher transfection efficiency for
      Poly3 and Poly4 grafted oligolysines than for Poly5, Poly2, and linear PLL.

PMID- 21961939
TI  - Development of a set of compensating Triticum aestivum-Dasypyrum villosum
      Robertsonian translocation lines.
AB  - Dasypyrum villosum  (L.) Candargy, a wild relative of bread wheat ( Triticum
      aestivum  L.), is the source of many agronomically important genes for wheat
      improvement. Production of compensating Robertsonian translocations (cRobTs),
      consisting of D. villosum chromosome arms translocated to homoeologous wheat
      chromosome arms, is one of the initial steps in exploiting this variation. The
      cRobTs for D. villosum chromosomes 1V, 4V, and 6V have been reported previously.
      Here we report attempted cRobTs for wheat - D. villosum chromosome combinations
      2D/2V, 3D/3V, 5D/5V, and 7D/7V. The cRobTs for all D. villosum chromosomes were
      recovered except for the 2VS and 5VL arms. As was the case with the 6D/6V
      combination, no cRobTs involving 2D/2V chromosomes were recovered; instead, cRobT
      T2BS.2VL involving a nontargeted chromosome was recovered. All cRobTs are
      fertile, although the level of spike fertility and hundred kernel weight (HKW)
      varied among the lines. The set of cRobTs involving 12 of the 14 D. villosum
      chromosomes will be useful in wheat improvement programs. In fact, among the
      already reported cRobTs, T6AL.6VS carrying the Pm21 gene is deployed in
      agriculture and many useful genes have been reported on other cRobTs including
      resistance to stem rust race UG99 on T6AS.6VL.

PMID- 21961940
TI  - Photoelectrochemical studies of DNA-tagged biomolecules on Au and Au/Ni/Au
      multilayer nanowires.
AB  - The use of nanowires (NWs) for labeling, sensing, and sorting is the basis of
      detecting biomolecules attached on NWs by optical and magnetic properties. In
      spite of many advantages, the use of biomolecules-attached NWs sensing by
      photoelectrochemical (PEC) study is almost non-existent. In this article, the PEC
      study of dye-attached single-stranded DNA on Au NWs and Au-Ni-Au multilayer NWs
      prepared by pulse electrodeposition are investigated. Owing to quantum-quenching
      effect, the multilayer Au NWs exhibit low optical absorbance when compared with
      Au NWs. The tagged Au NWs show good fluorescence (emission) at 570 nm, indicating
      significant improvement in the reflectivity. Optimum results obtained for tagged
      Au NWs attached on functionalized carbon electrodes and its PEC behavior is also
      presented. A twofold enhancement in photocurrent is observed with an average dark
      current of 10 MUA for Au NWs coated on functionalized sensing electrode. The
      importance of these PEC and optical studies provides an inexpensive and facile
      processing platform for Au NWs that may be suitable for biolabeling applications.

PMID- 21961942
TI  - Functional analysis of guinea pig beta1-adrenoceptor.
AB  - Although similarity of pharmacological responses to certain stimuli between
      guinea pigs and humans has been reported, this has been poorly defined by a
      molecular biological approach. In this study, we cloned the gene of guinea pig ?1
      adrenoceptor (ADRB1). The deduced amino acid sequence of guinea pig ADRB1 (467
      aa) showed 91% and 92% identity with the human and rat ADRB1 sequences,
      respectively. Using HEK293T cells expressing guinea pig, human and rat ADRB1s
      independently, we elucidated the functional characteristics of each ADRB1. The
      ligand-binding profiles and the concentration-response relationships for
      isoprenaline-induced cyclic adenosine monophosphate (cAMP) production were
      similar among the three ADRB1s. Isoprenaline also induced phosphorylation of
      extracellular-signal related kinases (ERK) through ADRB1s in a concentration
      dependent manner. The minimum effective concentration of isoprenaline for
      phosphorylation of ERK, through guinea pig ADRB1 was the same as through human
      ADRB1, but markedly lower than that of through rat ADRB1. ERK phosphorylation
      through guinea pig ADRB1 was sensitive to pertussis toxin, a dominant-negative
      ras and PD98059, indicating that a G(i)-mediated pathway is involved in the
      ADRB1/ERK signaling loop. These results suggest that the G(i)-coupling efficacy
      of guinea pig and human ADRB1s may be higher than that of rat ADRB1.

PMID- 21961941
TI  - Anidulafungin compared with fluconazole for treatment of candidemia and other
      forms of invasive candidiasis caused by Candida albicans: a multivariate analysis
      of factors associated with improved outcome.
AB  - BACKGROUND: Candida albicans is the most common cause of candidemia and other
      forms of invasive candidiasis. Systemic infections due to C. albicans exhibit
      good susceptibility to fluconazole and echinocandins. However, the echinocandin
      anidulafungin was recently demonstrated to be more effective than fluconazole for
      systemic Candida infections in a randomized, double-blind trial among 245
      patients. In that trial, most infections were caused by C. albicans, and all
      respective isolates were susceptible to randomized study drug. We sought to
      better understand the factors associated with the enhanced efficacy of
      anidulafungin and hypothesized that intrinsic properties of the antifungal agents
      contributed to the treatment differences. METHODS: Global responses at end of
      intravenous study treatment in patients with C. albicans infection were compared
      post-hoc. Multivariate logistic regression analyses were performed to predict
      response and to adjust for differences in independent baseline characteristics.
      Analyses focused on time to negative blood cultures, persistent infection at end
      of intravenous study treatment, and 6-week survival. RESULTS: In total, 135
      patients with C. albicans infections were identified. Among these, baseline
      APACHE II scores were similar between treatment arms. In these patients, global
      response was significantly better for anidulafungin than fluconazole (81.1% vs
      62.3%; 95% confidence interval [CI] for difference, 3.7-33.9). After adjusting
      for baseline characteristics, the odds ratio for global response was 2.36 (95%
      CI, 1.06-5.25). Study treatment and APACHE II score were significant predictors
      of outcome. The most predictive logistic regression model found that the odds
      ratio for study treatment was 2.60 (95% CI, 1.14-5.91) in favor of anidulafungin,
      and the odds ratio for APACHE II score was 0.935 (95% CI, 0.885-0.987), with
      poorer responses associated with higher baseline APACHE II scores. Anidulafungin
      was associated with significantly faster clearance of blood cultures (log-rank p
      < 0.05) and significantly fewer persistent infections (2.7% vs 13.1%; p < 0.05).
      Survival through 6 weeks did not differ between treatment groups. CONCLUSIONS: In
      patients with C. albicans infection, anidulafungin was more effective than
      fluconazole, with more rapid clearance of positive blood cultures. This suggests
      that the fungicidal activity of echinocandins may have important clinical
      implications. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00058682.

PMID- 21961943
TI  - Increased expression of S100 calcium binding protein A8 in GM-CSF-stimulated
      neutrophils leads to the increased expressions of IL-8 and IL-16.
AB  - OBJECTIVES: In our previous proteomic surveillance, we found that at least 11
      proteins in neutrophils were increased more than 2.5-fold by the stimulation of
      GM-CSF. In this paper, focusing on one of the 11 proteins, S100 calcium binding
      protein A8 (S100A8), we tried to elucidate the effect of S100A8 and the
      cooperative effect of S100A8 and GM-CSF on production and secretion of cytokines
      of neutrophils. METHODS: S100A8 in neutrophil was detected by western blotting,
      and concentrations of S100A8 in synovial fluid (SF) from patients with rheumatoid
      arthritis (RA) and osteoarthritis (OA) were measured by ELISA. Cytokine levels in
      the culture medium of neutrophils incubated with and without S100A8 were measured
      by an antibody array. IL-8 and IL-16 levels in the culture medium of neutrophils
      stimulated with S100A8, GM-CSF, and the combination of S100A8 and GM-CSF were
      measured by ELISA. The mRNA levels of IL-8 and IL-16 in the stimulated
      neutrophils were analysed by real-time PCR. RESULTS: The western blotting
      analysis confirmed that S100A8 is up-regulated in neutrophil by the stimulation
      of GM-CSF. Furthermore, the ELISA analysis confirmed that S100A8 was
      significantly elevated in SF of patients with RA compared to SF of patients with
      OA. S100A8 induced mRNA expression and secretion of IL-8 and IL-16. S100A8
      further enhanced production of IL-8 by GM-CSF but not that of IL-16. CONCLUSIONS:
      These data suggest that S100A8 may be involved in the exacerbation of RA, and
      that S100A8 may be a therapeutic target of RA.

PMID- 21961944
TI  - Nucleoside-lipid-based nanoparticles for cisplatin delivery.
AB  - The use of delivery vehicles to selectively transport anticancer agents to tumors
      is very attractive to address both toxicity and efficacy issues. We report a
      novel approach based on hybrid nucleoside-lipids allowing the efficient
      encapsulation and delivery of cisplatin. We demonstrate that the nucleoside polar
      heads guide the self-assembly of the aggregates into highly loaded and stable
      nanoparticles. The nanoparticles, which are efficient vehicles for the delivery
      of cisplatin into different sensitive and resistant cancer cell lines, can
      overcome the disadvantages and limitations of drug delivery systems previously
      reported.

PMID- 21961945
TI  - The rise and fall of job analysis and the future of work analysis.
AB  - This review begins by contrasting the importance ascribed to the study of
      occupational requirements observed in the early twentieth-century beginnings of
      industrial-organizational psychology with the diminishing numbers of job analysis
      articles appearing in top journals in recent times. To highlight the many pending
      questions associated with the job-analytic needs of today's organizations that
      demand further inquiry, research on the three primary types of job analysis data,
      namely work activities, worker attributes, and work context, is reviewed.
      Research on competencies is also reviewed along with the goals of a potential
      research agenda for the emerging trend of competency modeling. The cross
      fertilization of job analysis research with research from other domains such as
      the meaning of work, job design, job crafting, strategic change, and
      interactional psychology is proposed as a means of responding to the demands of
      today's organizations through new forms of work analysis.

PMID- 21961946
TI  - Remembering in conversations: the social sharing and reshaping of memories.
AB  - People constantly talk about past experiences. Burgeoning psychological research
      has examined the role of communication in remembering by placing rememberers in
      conversational settings. In reviewing this work, we first discuss the benefits of
      collaborative remembering (transactive memory and collaborative facilitation) and
      its costs (collaborative inhibition, information sampling biases, and audience
      tuning). We next examine how conversational remembering affects subsequent
      memory. Here, we address influences on listeners' memory through social
      contagion, resistance to such influences, and then retrieval/reexposure effects
      on either speaker or listener, with a focus on retrieval-induced forgetting.
      Extending the perspective beyond single interactions, we consider work that has
      explored how the above effects can spread across networks of several individuals.
      We also explore how a speaker's motive to form a shared reality with listeners
      can moderate conversational effects on memory. Finally, we discuss how these
      various conversational effects may promote the formation of collective memories.

PMID- 21961947
TI  - Working memory: theories, models, and controversies.
AB  - I present an account of the origins and development of the multicomponent
      approach to working memory, making a distinction between the overall theoretical
      framework, which has remained relatively stable, and the attempts to build more
      specific models within this framework. I follow this with a brief discussion of
      alternative models and their relationship to the framework. I conclude with
      speculations on further developments and a comment on the value of attempting to
      apply models and theories beyond the laboratory studies on which they are
      typically based.

PMID- 21961948
TI  - Evaluating headspace component vapor-time profiles by solid-phase microextraction
      with external sampling of an internal standard.
AB  - The vapor-time profiles of explosive materials are of valuable interest to
      Homeland Security, providing critical information that can aid in the detection
      of explosive-containing devices. An approach is described that achieves
      reproducible characterization of volatile components as a function of time based
      on comparison of the sample response to an externally sampled internal standard
      (ESIS). Utilizing nonequilibrium solid-phase microextraction (SPME) measurements,
      this SPME-ESIS technique improves reproducibility (reported as percent relative
      standard deviation) of vapor-time profiles by approximately an order of magnitude
      and allows for an equitable comparison of the target compound between diverse
      materials. Two odorants associated with canine detection of explosives, 2-ethyl-1
      hexanol and 2,4-dinitrotoluene, are used to optimize parameters for the SPME-ESIS
      technique.

PMID- 21961949
TI  - DiAlert: a lifestyle education programme aimed at people with a positive family
      history of type 2 diabetes and overweight, study protocol of a randomised
      controlled trial.
AB  - BACKGROUND: Family history is a known risk factor for type 2 diabetes (T2DM), and
      more so in the presence of overweight. This study aims to develop and evaluate
      the effectiveness of a new lifestyle education programme 'DiAlert' targeted at
      1st degree relatives of people with T2DM and overweight. In view of the high risk
      for diabetes and cardiovascular disease in immigrants from Turkish origin living
      in Western Europe, a culturally appropriate Turkish version of DiAlert will be
      developed and tested. METHODS/DESIGN: In this RCT, 268 (134 Dutch and 134
      Turkish) overweight 1st degree relatives of patients with T2DM will be allocated
      to either the intervention or control group (leaflet). The intervention DiAlert
      aims to promote intrinsic motivation to change lifestyle, and sustain achieved
      behaviour changes during follow-up. Primary outcome is weight loss. Secondary
      outcomes include biological, behavioural and psychological indices, along with
      process indicators. Measurements will take place at baseline and after 3 and 9
      months. Changes in outcomes are tested between intervention and control group at
      3 months; effects over time are tested within and between both ethnic groups at 3
      and 9 months. DISCUSSION: The DiAlert intervention is expected to be more
      effective than the control condition in achieving significant weight loss at 3
      months, in both Dutch and Turkish Dutch participants. TRIAL REGISTRATION:
      Netherlands National Trial Register (NTR): NTR2036.

PMID- 21961953
TI  - Toward the synthesis of norzoanthamine: building carbocyclic core by a
      transannular Michael reaction cascade.
AB  - A 12-step synthesis of the ABC carbocyclic core of norzoanthamine is described.
      It features an organocatalytic asymmetric intramolecular aldolization to set the
      stereochemistry of the entire molecule, a fragment coupling by selective
      alkylation of a bis-enolate, and a transannular Michael reaction cascade for
      rapid and stereoselective synthesis of the polycyclic core.

PMID- 21961954
TI  - Real-time monitoring of intracellular wax ester metabolism.
AB  - BACKGROUND: Wax esters are industrially relevant molecules exploited in several
      applications of oleochemistry and food industry. At the moment, the production
      processes mostly rely on chemical synthesis from rather expensive starting
      materials, and therefore solutions are sought from biotechnology. Bacterial wax
      esters are attractive alternatives, and especially the wax ester metabolism of
      Acinetobacter sp. has been extensively studied. However, the lack of suitable
      tools for rapid and simple monitoring of wax ester metabolism in vivo has partly
      restricted the screening and analyses of potential hosts and optimal conditions.
      RESULTS: Based on sensitive and specific detection of intracellular long-chain
      aldehydes, specific intermediates of wax ester synthesis, bacterial luciferase
      (LuxAB) was exploited in studying the wax ester metabolism in Acinetobacter
      baylyi ADP1. Luminescence was detected in the cultivation of the strain producing
      wax esters, and the changes in signal levels could be linked to corresponding
      cell growth and wax ester synthesis phases. CONCLUSIONS: The monitoring system
      showed correlation between wax ester synthesis pattern and luminescent signal.
      The system shows potential for real-time screening purposes and studies on
      bacterial wax esters, revealing new aspects to dynamics and role of wax ester
      metabolism in bacteria.

PMID- 21961955
TI  - Executive function performance on the children's kitchen task assessment with
      children with sickle cell disease and matched controls.
AB  - OBJECTIVE: The aim of this study was to compare executive function abilities of 8
      to 12-year-old children with sickle cell disease (SCD) with a matched control
      sample. The measures included the parent and teacher Behavior Rating Inventory of
      Executive Function (BRIEF); the Delis-Kaplan Executive Function System (D-KEFS),
      Free Sorting Test and Color Word Interference Test; and the Children's Kitchen
      Task Assessment (CKTA), a new performance measure. METHODS: Twenty-two children
      with SCD were recruited from one hematology clinic and 22 community children,
      matched on characteristics of age, gender, and race, were selected from a larger
      sample of controls for comparison. Parents and teachers completed rating scales.
      RESULTS: As hypothesized, children with SCD scored significantly lower than
      matched controls on Digit Span Forward; on 5 of the 9 D-KFES Color Word
      Interference and Sorting tasks; on CKTA organization, initiation, and task
      completion; and on the BRIEF's parent and teacher Metacognitive Index (MI) and
      Global Executive Composite (GEC) scores. CONCLUSION: Cognitive and performance
      evaluations indicate lower executive function among children with SCD. Results
      substantiate the need for evaluative triangulation for children with SCD:
      Neurocognitive testing supported by performance testing, and adult reflection of
      a child's daily performance compared to other children. These elements will
      provide rich data to create educational support for children with SCD who have
      frequent hospitalizations, school absences, and the potential presence of
      cerebral vascular accident symptomology.

PMID- 21961956
TI  - CpG site degeneration triggered by the loss of functional constraint created a
      highly polymorphic macaque drug-metabolizing gene, CYP1A2.
AB  - BACKGROUND: Elucidating the pattern of evolutionary changes in drug-metabolizing
      genes is an important subject not only for evolutionary but for biomedical
      research. We investigated the pattern of divergence and polymorphisms of macaque
      CYP1A1 and CYP1A2 genes, which are major drug-metabolizing genes in humans. In
      humans, CYP1A2 is specifically expressed in livers while CYP1A1 has a wider gene
      expression pattern in extrahepatic tissues. In contrast, macaque CYP1A2 is
      expressed at a much lower level than CYP1A1 in livers. Interestingly, a previous
      study has shown that Macaca fascicularis CYP1A2 harbored unusually high genetic
      diversity within species. Genomic regions showing high genetic diversity within
      species is occasionally interpreted as a result of balancing selection, where
      natural selection maintains highly diverged alleles with different functions.
      Nevertheless many other forces could create such signatures. RESULTS: We found
      that the CYP1A1/2 gene copy number and orientation has been highly conserved
      among mammalian genomes. The signature of gene conversion between CYP1A1 and
      CYP1A2 was detected, but the last gene conversion event in the simian primate
      lineage occurred before the Catarrhini-Platyrrhini divergence. The high genetic
      diversity of macaque CYP1A2 therefore cannot be explained by gene conversion
      between CYP1A1 and CYP1A2. By surveying CYP1A2 polymorphisms in total 91 M.
      fascicularis and M. mulatta, we found several null alleles segregating in these
      species, indicating functional constraint on CYP1A2 in macaques may have weakened
      after the divergence between humans and macaques. We propose that the high
      genetic diversity in macaque CYP1A2 is partly due to the degeneration of CpG
      sites, which had been maintained at a high level by purifying selection, and the
      rapid degeneration process was initiated by the loss of functional constraint on
      macaque CYP1A2. CONCLUSIONS: Our findings show that the highly polymorphic CYP1A2
      gene in macaques has not been created by balancing selection but by the burst of
      CpG site degeneration after loss of functional constraint. Because the functional
      importance of CYP1A1/2 genes is different between humans and macaques, we have to
      be cautious in extrapolating a drug-testing data using substrates metabolized by
      CYP1A genes from macaques to humans, despite of their somewhat overlapping
      substrate specificity.

PMID- 21961958
TI  - Conference report. International Conference ISOTOPES 2011, June 20-24, Greoux-les
      Bains, France.

PMID- 21961957
TI  - Chinese herbal extracts of Rubia cordifolia and Dianthus superbus suppress IgE
      production and prevent peanut-induced anaphylaxis.
AB  - BACKGROUND: Peanut allergy is characterized by increased levels of peanut
      specific IgE in the serum of most patients. Thus, the most logical therapy would
      be to inhibit the IgE production by committed B-cells. This study aims to
      investigate the unreported anti-IgE effects of Chinese herbal extracts of Rubia
      cordifolia (Qiancao) and Dianthus superbus (Qumai). METHODS: Seventy herbal
      extracts were tested for their ability to reduce IgE secretion by a human B-cell
      line. Those with the lowest inhibitory concentration 50 (IC50) values were tested
      in a mouse model of peanut-anaphylaxis. Anaphylactic scores, body temperature,
      plasma histamine and peanut-specific-immunoglobulins were determined. RESULTS:
      Rubia cordifolia and Dianthus superbus inhibited the in vitro IgE production by a
      human B-cell line in a dose-dependent manner and the in vivo IgE production in a
      murine model of peanut allergy without affecting peanut-specific-IgG1 levels.
      After challenge, all mice in the sham groups developed anaphylactic reactions and
      increased plasma histamine levels. The extract-treated mice demonstrated
      significantly reduced peanut-triggered anaphylactic reactions and plasma
      histamine levels. CONCLUSION: The extracts of Rubia cordifolia and Dianthus
      superbus inhibited the IgE production in vivo and in vitro as well as reduced
      anaphylactic reactions in peanut-allergic mice, suggesting potentials for allergy
      treatments.

PMID- 21961959
TI  - What is the Golgi apparatus, and why are we asking?

PMID- 21961960
TI  - Parylene insulated probes for scanning electrochemical-atomic force microscopy.
AB  - Scanning electrochemical-atomic force microscopy (SECM-AFM) is a powerful
      technique that can be used to obtain in situ information related to
      electrochemical phenomena at interfaces. Fabrication of probes to perform SECM
      AFM experiments remains a challenge. Herein, we describe a method for formation
      of microelectrodes at the tip of commercial conductive AFM probes and demonstrate
      application of these probes to SECM-AFM. Probes were first insulated with a thin
      parylene layer, followed by subsequent exposure of active electrodes at the probe
      tips by mechanical abrasion of the insulating layer. Characterization of probes
      was performed by electron microscopy and cyclic voltammetry. In situ measurement
      of localized electrochemical activity with parylene-coated probes was
      demonstrated through measurement of the diffusion of Ru(NH)(6)(3+) across a
      porous membrane.

PMID- 21961961
TI  - Flocculated amorphous itraconazole nanoparticles for enhanced in vitro
      supersaturation and in vivo bioavailability.
AB  - Rapid flocculation of nanoparticle dispersions of a poorly water soluble drug,
      itraconazole (Itz), was utilized to produce amorphous powders with desirable
      dissolution properties for high bioavailability in rats. Antisolvent
      precipitation (AP) was utilized to form Itz nanodispersions with high drug
      loadings stabilized with hydroxypropylmethylcellulose (HPMC) or the pH-sensitive
      Eudragit((r)) L100-55 (EL10055). The HPMC dispersions were flocculated by
      desolvating the polymer through the addition of a divalent salt, and the enteric
      EL10055 by reducing the pH. The formation of open flocs by diffusion limited
      aggregation facilitated redispersion of the flocs at pH 6.8. Upon redispersion of
      the flocculated nanoparticles at pH 6.8, the particle size was modestly larger
      than the original size, on the order of 1 MUm. High in vitro supersaturation
      (AUC) of the flocculated nanoparticle dispersions was observed in micellar media
      at pH 6.8, after 2 hours initial exposure at pH 1.2 to simulate the stomach,
      relative to the AUC for a commercially available Itz formulation, Sporanox.
      Greater in vivo bioavailability in rats was correlated directly to the higher in
      vitro AUC at pH 6.8 with micelles during the pH shift experiment for the
      flocculated nanoparticle dispersions relative to Sporanox. The ability to
      generate and sustain high supersaturation in micellar media at pH 6.8, as shown
      with the in vitro pH shift dissolution test, is beneficial for increasing
      bioavailability of Itz by oral delivery.

PMID- 21961962
TI  - Factors associated with hearing preservation after Gamma Knife surgery for
      vestibular schwannomas in patients who retain serviceable hearing.
AB  - OBJECT: Gamma Knife surgery (GKS) has been a safe and effective treatment for
      small- to medium-sized vestibular schwannomas (VSs) over relatively long-term
      outcomes. However, even with recent radiosurgical techniques, hearing results
      following GKS remain unsatisfactory. The purpose of this study was to evaluate
      the hearing preservation rate as well as factors related to hearing preservation
      in patients with VSs and serviceable hearing who were treated with GKS. METHODS:
      Among patients with Gardner-Robertson (GR) Class I or II serviceable hearing and
      VSs treated with GKS between 1991 and 2009, 117 were evaluable via periodic MR
      imaging and audiometry. RESULTS: The median age at the time of GKS was 52 years.
      Four patients (3%) had undergone prior surgery. Fifty-six patients (48%) had GR
      Class I hearing and 61 (52%) had GR Class II hearing at the time of GKS. The
      median tumor volume was 1.9 cm(3). The median maximum and tumor margin radiation
      doses were 24 and 12 Gy, respectively. The median follow-up periods for MR
      imaging and audiometry were 74 and 38 months, respectively. The overall tumor
      control rate was 97.5%. Actuarial 3-, 5-, and 8-year hearing preservation rates
      were 55%, 43%, and 34%, respectively. On multivariate analysis, GR hearing class
      at the time of GKS and the mean cochlear dose affected hearing preservation
      significantly. In a limited number of patients who were treated using the most
      recent dose planning techniques and who had GR Class I hearing before treatment,
      the 3- and 5-year hearing preservation rates increased to 80% and 70%,
      respectively. CONCLUSIONS: For the majority of patients with small- to medium
      sized VSs, GKS was an effective and reasonable alternative to resection with
      satisfactory long-term tumor control. Factors related to hearing preservation
      included a GR Class I hearing pre-GKS and a lower mean cochlear radiation dose.
      To retain serviceable hearing, it is important to apply GKS treatment while
      patients retain GR Class I hearing.

PMID- 21961964
TI  - Midterm outcome after a microsurgical unilateral approach for bilateral
      decompression of lumbar degenerative spondylolisthesis.
AB  - OBJECT: The aim of this study was to evaluate the results and effectiveness of
      bilateral decompression via a unilateral approach in the treatment of lumbar
      degenerative spondylolisthesis (DS). METHODS: Operations were performed in 84
      selected patients (mean age 62.1 +/- 10 years) with lumbar DS between the years
      2001 and 2008. The selection criteria included lower back pain with or without
      sciatica, neurogenic claudication that had not improved after at least 6 months
      of conservative treatment, and a radiological diagnosis of Grade I DS and lumbar
      stenosis. Decompression was performed at 3 levels in 15.5%, 2 levels in 54.8%,
      and 1 level in 29.7% of the patients with 1 level of spondylolisthesis. All
      patients were followed up for at least 24 months. For clinical evaluations, a
      visual analog scale, Oswestry Disability Index (ODI), and Neurogenic Claudication
      Outcome Score (NCOS) were used. Spinal canal size and (neutral and dynamic) slip
      percentages were measured both pre- and postoperatively. RESULTS: Neutral and
      dynamic slip percentages did not significantly change after surgery (p = 0.67 and
      p = 0.63, respectively). Spinal canal size increased from 50.6 +/- 5.9 to 102.8
      +/- 9.5 mm(2) (p < 0.001). The ODI decreased significantly in both the early and
      late follow-up evaluations, and good or excellent results were obtained in 64
      cases (80%). The NCOS demonstrated significant improvement in the late follow-up
      results (p < 0.001). One patient (1.2%) required secondary fusion during the
      follow-up period. CONCLUSIONS: Postoperative clinical improvement and
      radiological findings clearly demonstrated that the unilateral approach for
      treating 1-level and multilevel lumbar spinal stenosis with DS is a safe,
      effective, and minimally invasive method in terms of reducing the need for
      stabilization.

PMID- 21961963
TI  - Virologic and clinical characteristics of HBV genotypes/subgenotypes in 487
      Chinese pediatric patients with CHB.
AB  - BACKGROUND: The association of hepatitis B virus (HBV) genotypes/subgenotypes
      with clinical characteristics is increasingly recognized. However, the virologic
      and clinical features of HBV genotypes/subgenotypes in pediatric patients remain
      largely unknown. METHODS: Four hundred and eighty-seven pediatric inpatients with
      CHB were investigated, including 217 nucleos(t)ide analog-experienced patients.
      HBV genotypes/subgenotypes and reverse transcriptase (RT) mutations were
      determined by direct sequencing. The stage of fibrosis and degree of inflammatory
      activity were evaluated by the Metavir score system. RESULTS: Among 487 enrolled
      pediatric patients, HBV genotype C2 and B2 were the most two prevalent (73.7% and
      21.1%). Comparing with HBV/B2 infected patients, no significant difference was
      observed in the incidence rate and mutant patterns of lamivudine- or adefovir
      resistant mutations in HBV/C2 infected patients (P > 0.05). Importantly, we found
      that the degree of hepatic inflammation degree, fibrosis stage and ALT level were
      significantly higher in HBV/C2-infected HBeAg positive patients than it was in
      HBV/B2-infected ones. CONCLUSIONS: The pediatric patients with HBV/C2 infection
      might be more susceptible to develop severe liver pathogenesis.

PMID- 21961965
TI  - Supersensitization of CdS quantum dots with a near-infrared organic dye: toward
      the design of panchromatic hybrid-sensitized solar cells.
AB  - The photoresponse of quantum dot solar cells (QDSCs) has been successfully
      extended to the near-IR (NIR) region by sensitizing nanostructured TiO(2)-CdS
      films with a squaraine dye (JK-216). CdS nanoparticles anchored on mesoscopic
      TiO(2) films obtained by successive ionic layer adsorption and reaction (SILAR)
      exhibit limited absorption below 500 nm with a net power conversion efficiency of
      ~1% when employed as a photoanode in QDSC. By depositing a thin barrier layer of
      Al(2)O(3), the TiO(2)-CdS films were further modified with a NIR absorbing
      squaraine dye. Quantum dot sensitized solar cells supersensitized with a
      squariand dye (JK-216) showed good stability during illumination with standard
      global AM 1.5 solar conditions, delivering a maximum overall power conversion
      efficiency (eta) of 3.14%. Transient absorption and pulse radiolysis measurements
      provide further insight into the excited state interactions of squaraine dye with
      SiO(2), TiO(2), and TiO(2)/CdS/Al(2)O(3) films and interfacial electron transfer
      processes. The synergy of combining semiconductor quantum dots and NIR absorbing
      dye provides new opportunities to harvest photons from different regions of the
      solar spectrum.

PMID- 21961966
TI  - Association of programmed cell death-1 (PDCD-1) gene polymorphisms with
      rheumatoid arthritis in Iranian patients.
AB  - OBJECTIVES: Programmed cell death 1 (PDCD-1, also named PD-1, CD279, and SLEB2),
      a negative T cell regulator to maintain peripheral tolerance, induces negative
      signals to T cells during interaction with its ligands and is therefore a
      candidate gene in the development of autoimmune diseases such as rheumatoid
      arthritis (RA). Herein, we investigate the association of PDCD-1 polymorphisms
      with the risk of RA among Iranian patients and healthy controls. METHODS: Genomic
      DNA was extracted from the whole blood samples using DNA Purification kit (DNG
      plus). Using the PCR- RFLP method, 3 PDCD-1 SNPs, including PD1.1G/A, PD1.3G/A,
      and PD1.9C/T were genotyped in 120 RA patients as well as 188 healthy controls.
      The genotype and allele frequencies of these SNPs were analysed by statistical
      tests for the significant association between RA patients and controls. Haplotype
      constructions of these SNPs were performed. Clinical diagnosis of the RA patients
      was confirmed by the Rheumatology Research Centere of Tehran University of
      Medical Sciences. RESULTS: Our study revealed that PD1.1 A allele at position 
      538 in the promoter region of PDCD-1 gene is associated with an increased risk of
      RA disease compared to controls (2.9% vs. 0.7%, OR= 3.735, 95% CI= 0.956-14.588,
      p=0.046). There were no significant differences in other alleles and genotypes of
      PDCD-1 SNPs between RA cases and controls. CONCLUSIONS: Our results indicate that
      among the polymorphisms which we evaluated only the PD1.1A allele in the promoter
      region of PDCD-1 gene is significantly associated with RA susceptibility in
      Iranian patients.

PMID- 21961967
TI  - Specific issues in small animal dosimetry and irradiator calibration.
AB  - PURPOSE: In response to the increased risk of radiological terrorist attack, a
      network of Centers for Medical Countermeasures against Radiation (CMCR) has been
      established in the United States, focusing on evaluating animal model responses
      to uniform, relatively homogenous whole- or partial-body radiation exposures at
      relatively high dose rates. The success of such studies is dependent not only on
      robust animal models but on accurate and reproducible dosimetry within and across
      CMCR. To address this issue, the Education and Training Core of the Duke
      University School of Medicine CMCR organised a one-day workshop on small animal
      dosimetry. Topics included accuracy in animal dosimetry accuracy, characteristics
      and differences of cesium-137 and X-ray irradiators, methods for dose
      measurement, and design of experimental irradiation geometries for uniform dose
      distributions. This paper summarises the information presented and discussed.
      CONCLUSIONS: Without ensuring accurate and reproducible dosimetry the development
      and assessment of the efficacy of putative countermeasures will not prove
      successful. Radiation physics support is needed, but is often the weakest link in
      the small animal dosimetry chain. We recommend: (i) A user training program for
      new irradiator users, (ii) subsequent training updates, and (iii) the
      establishment of a national small animal dosimetry center for all CMCR members.

PMID- 21961968
TI  - Modern dosimetric tools for (60)Co irradiation at high containment laboratories.
AB  - PURPOSE: To evaluate an innovative photo-fluorescent film as a routine dosimetric
      tool during (60)Co irradiations at a high containment biological research
      laboratory, and to investigate whether manufacturer-provided chamber exposure
      rates can be used to accurately administer a prescribed dose to biological
      specimens. MATERIALS AND METHODS: Photo-fluorescent, lithium fluoride film
      dosimeters and National Institutes of Standards and Technology (NIST) transfer
      dosimeters were co-located in a self-shielded (60)Co irradiator and exposed to
      gamma-radiation with doses ranging from 5-85 kGy. Film dose-response
      relationships were developed for varying temperatures simulating conditions
      present when irradiating infectious biological specimens. Dose measurement
      results from NIST transfer dosimeters were compared to doses predicted using
      manufacturer-provided irradiator chamber exposure rates. RESULTS: The film
      dosimeter exhibited a photo-fluorescent response signal that was consistent and
      nearly linear in relationship to gamma-radiation exposure over a wide dose range.
      The dosimeter response also showed negligible effects from dose fractionization
      and humidity. Significant disparities existed between manufacturer-provided
      chamber exposure rates and actual doses administered. CONCLUSION: This study
      demonstrates the merit of utilizing dosimetric tools to validate the process of
      exposing dangerous and exotic biological agents to gamma-radiation at high
      containment laboratories. The film dosimeter used in this study can be utilized
      to eliminate potential for improperly administering gamma-radiation doses.

PMID- 21961969
TI  - Calcium overload induces C6 rat glioma cell apoptosis in sonodynamic therapy.
AB  - PURPOSE: Our aim was to study calcium overload-induced apoptosis and its relation
      to reactive oxygen species (ROS) in rat C6 glioma cells after sonodynamic
      treatment (SDT). MATERIALS AND METHODS: Hematoporphyrin monomethyl ether (HMME)
      was used as the sonosensitizer. The concentration of intracellular Ca(2+)
      ([Ca(2+)](i)) was measured by fluorometry. Apoptosis and necrosis rates were
      evaluated by a flow cytometry. Moreover, sarcoplasmic reticulum Ca(2+) -ATPase
      (SERCA(2)), cytochrome c (cyto-c) and cleaved caspase-3 were investigated by
      immunoblotting. RESULTS: Our study indicated that [Ca(2 +)](i) and ROS increased
      in cells of SDT group, the apoptosis rate, quantity of cyto-c and cleaved caspase
      3 markedly increased after SDT. Furthermore, N-Acetyl-L-cysteine (NAC) or 1,2
      bisethane-N,N,N',N'-tetraacetic acid tetrakis ester (BAPTA-AM) could decrease the
      apoptosis rate, the release of cyto-c and cleaved caspase-3 in SDT group,
      SERCA(2) degradation was found in SDT group and could also be prevented by the
      addition of NAC. CONCLUSIONS: Our results show that HMME-SDT can induce C6 cell
      death through both necrosis and apoptosis. ROS in C6 cells play a decisive role
      in HMME-SDT-induced cell death. The endoplasmic reticulum (ER) may be a major
      target of HMME-SDT, ROS can induce SERCA(2) degradation, causing the elevation of
      [Ca(2+)](i).

PMID- 21961970
TI  - Comment on I. B. Erguder et al., "Effects of mobile phone use on brain tissue
      from the rat and a possible protective role of vitamin C - a preliminary study"
      [Int. J. Radiat. Biol. 86 (2010) 1044-1049].

PMID- 21961972
TI  - Multiplex screening of persistent organic pollutants in fish using spectrally
      encoded microspheres.
AB  - Persistent organic pollutants (POPs) are environmental and food-related
      contaminants of global public health concern and known to be carcinogenic and
      endocrine disruptors. Their monitoring is essential, and an easy-to-use, rapid,
      and affordable multianalyte screening method with simplified sample preparation
      can be a valuable tool prior to instrumental analysis. For this purpose, a flow
      cytometric immunoassay (FCIA), based on a spectrally encoded microbeads
      technology, was developed for the multiplex detection of polycyclic aromatic
      hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and polybrominated
      diphenyl ethers (BDEs) in buffer and fish extracts. The sensitivities of the
      assays in the three-plex FCIA format were similar to the individual FCIAs for the
      marker compounds benzo[a]pyrene (BaP), 3,3',4,4'-tetrachlorobiphenyl (PCB77), and
      2,2',4,4'-tetrabromodiphenyl ether (BDE47) in buffer with IC(50) values of 0.4,
      20, and 2 MUg L(-1), respectively. Apart from the three markers, we could detect
      at least 14 other POPs. Extracts of fish with different fat content, prepared
      with a simplified extraction and cleanup procedure, had an insignificant
      influence on the overall three-plex FCIA performance, with the exception of some
      impact on the PAHs detection. The performance of the three-plex FCIA, in
      combination with the simple extraction procedure, is adequate for regulatory
      control in accordance with the required limits.

PMID- 21961973
TI  - Interaction potentials of uranium cations with rare gases (RG) and transport of
      U+ in RG (RG = He, Ne, Ar, Kr, and Xe).
AB  - We present accurate interaction potentials for uranium cations interacting with
      the rare gases (RG = He-Rn), using effective core potentials that include a
      description of the 5f electrons in the case of uranium, and justify this
      approximation in some detail. From these interaction potentials, spectroscopic
      parameters are derived for the U(+)-RG complexes. We also employ the potentials
      to calculate transport coefficients for U(+) moving through a bath of each RG. In
      the case of U(+) in He, we are able to compare with previous experimentally
      determined mobility values, and we make some minor corrections to the previously
      reported data; this revised data is presented.

PMID- 21961978
TI  - Position statement by the Society of Interventional Radiology: maintenance of
      privileges for image-guided interventions.

PMID- 21961974
TI  - Stochastic proximity embedding on graphics processing units: taking
      multidimensional scaling to a new scale.
AB  - Stochastic proximity embedding (SPE) was developed as a method for efficiently
      calculating lower dimensional embeddings of high-dimensional data sets. Rather
      than using a global minimization scheme, SPE relies upon updating the distances
      of randomly selected points in an iterative fashion. This was found to generate
      embeddings of comparable quality to those obtained using classical
      multidimensional scaling algorithms. However, SPE is able to obtain these results
      in O(n) rather than O(n2) time and thus is much better suited to large data sets.
      In an effort both to speed up SPE and utilize it for even larger problems, we
      have created a multithreaded implementation which takes advantage of the growing
      general computing power of graphics processing units (GPUs). The use of GPUs
      allows the embedding of data sets containing millions of data points in
      interactive time scales.

PMID- 21961979
TI  - Embolization of parasitized extrahepatic arteries to reestablish intrahepatic
      arterial supply to tumors before yttrium-90 radioembolization.
AB  - PURPOSE: To perform embolization of parasitized extrahepatic arteries (EHAs)
      before radioembolization to reestablish intrahepatic arterial supply to large,
      peripheral tumors, and to evaluate the technical and clinical outcomes of this
      intervention. MATERIALS AND METHODS: Among 201 patients retrospectively analyzed,
      embolization of 73 parasitized EHAs in 35 patients was performed. Most
      embolization procedures were performed during preparatory angiography using large
      particles and coils. Digital subtraction angiography (DSA), C-arm computed
      tomography (CT), and technetium-99m macroaggregated albumin ((99m)TcMAA)
      scintigraphy were used to evaluate the immediate perfusion via intrahepatic
      collateral channels of target tumor areas previously supplied by parasitized
      EHAs. Follow-up imaging of differential regional tumor response was used to
      evaluate microsphere distribution and clinical outcome. RESULTS: After
      embolization, reestablishment of intrahepatic arterial supply was confirmed by
      both DSA and C-arm CT in 94% of territories and by scintigraphy in 96%. In 32% of
      patients, the differential response of treatment could not be evaluated because
      of uniform disease progression. However, symmetric regional tumor response in 94%
      of evaluable patients indicated successful delivery of microspheres to the
      territories previously supplied by parasitized EHAs. CONCLUSIONS: Reestablishment
      of intrahepatic arterial inflow to hepatic tumors by embolization of parasitized
      EHAs is safe and effective and results in successful delivery of yttrium-90
      microspheres to tumors previously perfused by parasitized EHAs.

PMID- 21961980
TI  - Invited commentary.

PMID- 21961981
TI  - Consolidation of hepatic arterial inflow by embolization of variant hepatic
      arteries in preparation for yttrium-90 radioembolization.
AB  - PURPOSE: Before yttrium-90 ((90)Y) radioembolization administration, the authors
      consolidated arterial inflow by embolizing variant hepatic arteries (HAs) to make
      microsphere delivery simpler and safer. The present study reviews the technical
      and clinical success of these consolidation procedures. MATERIALS AND METHODS:
      Preparatory and treatment angiograms were retrospectively analyzed for 201
      patients. Variant HAs were coil-embolized during preparatory angiography to
      simplify arterial anatomy. Collateral arterial perfusion of territories
      previously supplied by variant HAs was evaluated by digital subtraction
      angiography (DSA), C-arm computed tomography (CT), and technetium-99m ((99m)Tc)
      macroaggregated albumin (MAA) scintigraphy, and by follow-up evaluation of
      regional tumor response. RESULTS: A total of 47 variant HAs were embolized in 43
      patients. After embolization of variant HAs, cross-perfusion into the embolized
      territory was depicted by DSA and by C-arm CT in 100% of patients and by (99m)Tc
      MAA scintigraphy in 92.7%. Uniform progressive disease prevented evaluation in
      33% of patients, but regional tumor response in patients who responded supported
      successful delivery of microspheres to the embolized territories in 95.5% of
      evaluable patients. CONCLUSIONS: Embolization of variant HAs for consolidation of
      hepatic supply in preparation for (90)Y radioembolization promotes treatment of
      affected territories via intrahepatic collateral channels.

PMID- 21961982
TI  - MR imaging-guided cryoablation for the treatment of benign prostatic hyperplasia.
AB  - A patient with benign prostatic hyperplasia presented with chronic lower urinary
      tract symptoms despite prior surgery and continued medical therapy. Using a
      magnetic resonance imaging-guided transperineal approach, two cryoprobes were
      placed into the transition zone of the prostate gland, and two cryoablation
      freeze-thaw cycles were performed. At 10 weeks after treatment, the frequency of
      nocturia had decreased from once every 1.5 hours to once per night, urinary peak
      flow rates had increased from 5.1 mL/s to 10.3 mL/s, and postvoid residual
      urinary bladder volume had decreased from 187 mL to 58 mL. Improved flow rates
      and symptoms remained stable 16 weeks after treatment.

PMID- 21961983
TI  - Stent-assisted coil embolization of renal artery bifurcation aneurysm using the
      kissing stent technique.

PMID- 21961984
TI  - Skin and venous rupture at a hemodialysis needle cannulation site during
      angioplasty of a transposed forearm fistula.

PMID- 21961985
TI  - Uterine artery embolization for symptomatic adenomyosis in a patient with uterus
      didelphys.

PMID- 21961986
TI  - Peritoneal "pearl" mystery after uterine artery embolization.

PMID- 21961988
TI  - Interventions for maintenance in hemodialysis grafts with early failure.

PMID- 21961989
TI  - Canarene: a triterpenoid with a unique carbon skeleton from Canarium
      schweinfurthii.
AB  - Canarene (1), a triterpene with an unprecedented carbon backbone, was isolated
      from Canarium schweinfurthii . It is the first member of a new class of
      triterpenoids, for which the name "canarane'' is proposed. 1 showed weak alpha
      glucosidase inhibitory activity, and its structure was unambiguously deduced by
      single-crystal X-ray diffraction.

PMID- 21961990
TI  - Changes in vector species composition and current vector biology and behaviour
      will favour malaria elimination in Santa Isabel Province, Solomon Islands.
AB  - BACKGROUND: In 2009, Santa Isabel Province in the Solomon Islands embarked on a
      malaria elimination programme. However, very little is known in the Province
      about the anopheline fauna, which species are vectors, their bionomics and how
      they may respond to intensified intervention measures. The purpose of this study
      was to provide baseline data on the malaria vectors and to ascertain the
      possibility of successfully eliminating malaria using the existing conventional
      vector control measures, such as indoor residual spraying (IRS) and long-lasting
      insecticidal nets (LLIN). METHODS: Entomological surveys were undertaken during
      October 2009. To determine species composition and distribution larval surveys
      were conducted across on the whole island. For malaria transmission studies,
      adult anophelines were sampled using human landing catches from two villages -
      one coastal and one inland. RESULTS: Five Anopheles species were found on Santa
      Isabel: Anopheles farauti, Anopheles hinesorum, Anopheles lungae, Anopheles
      solomonis, and Anopheles nataliae. Anopheles hinesorum was the most widespread
      species. Anopheles farauti was abundant, but found only on the coast. Anopheles
      punctulatus and Anopheles koliensis were not found. Anopheles farauti was the
      only species found biting in the coastal village, it was incriminated as a vector
      in this study; it fed early in the night but equally so indoors and outdoors, and
      had a low survival rate. Anopheles solomonis was the main species biting humans
      in the inland village, it was extremely exophagic, with low survival rates, and
      readily fed on pigs. CONCLUSION: The disappearance of the two major vectors, An.
      punctulatus and An. koliensis, from Santa Isabel and the predominance of An.
      hinesorum, a non-vector species may facilitate malaria elimination measures.
      Anopheles farauti was identified as the main coastal vector with An. solomonis as
      a possible inland vector. The behaviour of An. solomonis is novel as it has not
      been previously found biting humans in any numbers. Both species appear to be
      short-lived, a characteristic that will limit their transmission potential. The
      early night feeding behaviour and a degree of outdoor biting seen in An. farauti
      and particularly in An. solomonis will require that their response to IRS and
      LLIN be closely monitored. In coastal villages, where large, favourable breeding
      sites allow for high numbers of An. farauti may require the addition of larval
      control to achieve elimination.

PMID- 21961991
TI  - Boswellic acids extract attenuates pulmonary fibrosis induced by bleomycin and
      oxidative stress from gamma irradiation in rats.
AB  - BACKGROUND: Interstitial pulmonary fibrosis is characterized by an altered
      cellular composition of the alveolar region with excessive deposition of
      collagen. Lung inflammation is also common in pulmonary fibrosis. This study aims
      to test the inhibition of 5-lipooxygenase (5-LOX) by boswellic acid (BA) extract
      in an experimental model of pulmonary fibrosis using bleomycin (BL). METHODS:
      Boswellic acid extract (1 g/kg) was force-fed to rats seven days prior to
      administration of BL or gamma irradiation or both. BL (0.15 U/rat) in 25 MUl of
      0.9% normal saline (NS) or 0.9% NS alone was administered intratracheally. Rats
      were exposed to two fractionated doses of gamma irradiation (0.5 Gy/dose/week)
      with a gamma cell-40 (Cesium-137 irradiation units, Canada) during the last two
      weeks of the experiment. BA was administered during BL or irradiation treatment
      or both. After the animals were sacrificed, bronchoalveolar lavage was performed;
      lungs were weighed and processed separately for biochemical and histological
      studies. RESULTS: In rats treated with BL, levels of transforming growth factor
      beta1 (TGF-beta1) and tumor necrosis factor-alpha (TNF-alpha) were significantly
      elevated (P = 0.05 and P = 0.005). Hydroxyproline was highly and extensively
      expressed. Immunoreactive compounds were abundantly expressed, represented in the
      levels of macrophages infiltrate, accumulation of eosinophils and neutrophils in
      the lung as well as the aggregation of fibroblasts in the fibrotic area. The
      levels of lipoxygenase enzyme activity were significantly increased (P = 0.005).
      Antioxidant activities measured in BL-treated rats deteriorated, coupled with the
      elevation of both levels of plasma lipid peroxide (LP) content and
      bronchoalveolar lavage lactate dehydrogenase activity. BA-treated rats had
      reduced number of macrophages, (P = 0.01), neutrophils in bronchoalveolar lavage
      (P = 0.01) and protein (P = 0.0001). Moreover, the hydroxyproline content was
      significantly lowered in BA-treated rats (P = 0.005). BA extract inhibited the
      TGF-beta induced fibrosis (P = 0.01) and 5-LOX activity levels (P =
      0.005).Histologically, BA reduced the number of infiltrating cells, ameliorated
      the destruction of lung architecture and attenuated lung fibrosis. CONCLUSION: BA
      attenuates the BL-induced injury response in rats, such as collagen accumulation,
      airway dysfunction and injury. This study suggests that the blocking of 5-LOX may
      prevent the progression of fibrosis.

PMID- 21961993
TI  - Executive functioning and psychological adjustment in children and youth with
      spina bifida.
AB  - Children and adolescents with spina bifida are at risk for poor
      neuropsychological functioning and psychological outcomes. The relationship
      between executive functioning and psychological adjustment is an area worthy of
      investigation in this population. The current study assessed executive
      functioning and psychological outcomes in a group of children and adolescents
      with spina bifida (SBM) (n = 51) and nondisabled controls (n = 45). A mediation
      model was hypothesized, such that Metacognition, as measured by the Behavior
      Rating Inventory of Executive Function (BRIEF), mediated the relationship between
      group status (spina bifida versus nondisabled controls) and psychological
      outcomes. Results indicated that metacognitive skills fully explained the
      relationship between group and internalizing and depressive symptoms as reported
      by mothers. In particular, specific components of the BRIEF Metacognition
      composite were most responsible for this relationship, including Initiate,
      Working Memory, and Plan/Organize. The study limitations include its cross
      sectional nature that precludes drawing conclusions about causality. The results
      have implications for treatment interventions for children and adolescents with
      spina bifida and typically developing individuals.

PMID- 21961994
TI  - Tableting properties of silica aerogel and other silicates.
AB  - CONTEXT: In solid oral dosage forms silicates are commonly used as glidants in
      low concentration. However, due to their large specific surface area, silicates
      may also be used as carrier materials for drugs. Moreover, silicates allow
      amorphisation of drugs by co-grinding or processing with supercritical fluids.
      OBJECTIVE: The aim of this study was to investigate the physical and the
      tableting properties of Silica Aerogel (special type of silica with an extremely
      large specific surface area), Neusilin((r)) US2 (magnesium aluminometasilicate),
      Florite((r)) (calcium silicate) and Aerosil((r)) 200 (colloidal silica).
      MATERIALS AND METHODS: Powder blends of Avicel((r)) PH102 (microcrystalline
      cellulose) and different amounts of the respective silicate were compacted and
      analyzed for their tabletability (tensile strength vs. compaction pressure) as
      well as their Heckel plot. RESULTS AND DISCUSSION: With Neusilin((r)) the
      tabletability appeared to be independent of the silicate concentration, whereas
      with Florite((r)) an increasing silicate concentration led to a higher tensile
      strength. In contrast, the addition of Silica Aerogel and Aerosil((r)) resulted
      in a decrease of the tensile strength. With Aerosil((r)) a maximum tolerable
      concentration of 20% [w/w] was determined. Plastic deformation of all powder
      blends decreased with increasing silicate concentration. This effect was most
      pronounced with Aerosil((r)) and least with Florite((r)). CONCLUSION: Tablets
      with acceptable tensile strength were obtained with all plain silicates except
      for Aerosil((r)). Therefore, these silicates may be used in tablet formulations,
      e.g. as carrier materials for liquid or amorphous drugs.

PMID- 21961995
TI  - Effects of ethinyl estradiol-cyproterone acetate treatment on metabolic syndrome,
      fat distribution and carotid intima media thickness in polycystic ovary syndrome.
AB  - OBJECTIVE: To evaluate the effects of ethinyl estradiol-cyproterone acetate (EE
      CA) treatment on metabolic and cardiovascular risk factors, and body fat
      distribution in polycystic ovary syndrome (PCOS) after 6-month treatment.
      SUBJECTS AND METHODS: Thirty women with PCOS were evaluated before and after 6
      months of EE-CA treatment. Anthropometrical measurements, hormonal levels, lipid
      and glucose profile were evaluated. Body fat thickness in four regions and
      carotid intima media thickness (IMT) were measured. Interval change in
      antropometric measurements, glucose and lipid profile, carotid IMT and body fat
      distribution was evaluated before and after 6-month EE-CA treatment. RESULTS:
      Ferriman-Gallwey score and serum testosterone levels were significantly decreased
      after EE-CA treatment (p < 0.01). No significant effect was detected on insulin
      resistance, lipid profile and carotid artery IMT. The visceral, subcutaneous and
      preperitoneal fat thicknesses decreased, and mid-thigh fat thickness increased
      after treatment period. However, only the alteration in subcutaneous fat
      thickness achieved a statistical significance (p < 0.01). CONCLUSION: The EE-CA
      is an effective regimen in treatment of hirsutism and menstrual regulation.
      Although it provides significant decrease in subcutaneous fat thickness after 6
      month treatment, it has no beneficial effect with respect to visceral fat
      thickness, metabolic and cardiovascular risk factors.

PMID- 21961992
TI  - Deciphering c-MYC-regulated genes in two distinct tissues.
AB  - BACKGROUND: The transcription factor MYC is a critical regulator of diverse
      cellular processes, including both replication and apoptosis. Differences in MYC
      regulated gene expression responsible for such opposing outcomes in vivo remain
      obscure. To address this we have examined time-dependent changes in global gene
      expression in two transgenic mouse models in which MYC activation, in either skin
      suprabasal keratinocytes or pancreatic islet beta-cells, promotes tissue
      expansion or involution, respectively. RESULTS: Consistent with observed
      phenotypes, expression of cell cycle genes is increased in both models (albeit
      enriched in beta-cells), as are those involved in cell growth and metabolism,
      while expression of genes involved in cell differentiation is down-regulated.
      However, in beta-cells, which unlike suprabasal keratinocytes undergo prominent
      apoptosis from 24 hours, there is up-regulation of genes associated with DNA
      damage response and intrinsic apoptotic pathways, including Atr, Arf, Bax and
      Cycs. In striking contrast, this is not the case for suprabasal keratinocytes,
      where pro-apoptotic genes such as Noxa are down-regulated and key anti-apoptotic
      pathways (such as Igf1-Akt) and those promoting angiogenesis are up-regulated.
      Moreover, dramatic up-regulation of steroid hormone-regulated Kallikrein serine
      protease family members in suprabasal keratinocytes alone could further enhance
      local Igf1 actions, such as through proteolysis of Igf1 binding proteins.
      CONCLUSIONS: Activation of MYC causes cell growth, loss of differentiation and
      cell cycle entry in both beta-cells and suprabasal keratinocytes in vivo.
      Apoptosis, which is confined to beta-cells, may involve a combination of a DNA
      damage response and downstream activation of pro-apoptotic signalling pathways,
      including Cdc2a and p19(Arf)/p53, and downstream targets. Conversely, avoidance
      of apoptosis in suprabasal keratinocytes may result primarily from the activation
      of key anti-apoptotic signalling pathways, particularly Igf1-Akt, and induction
      of an angiogenic response, though intrinsic resistance to induction of p19(Arf)
      by MYC in suprabasal keratinocytes may contribute.

PMID- 21961996
TI  - Rapid synthesis of stable and functional conjugates of DNA/gold nanoparticles
      mediated by Tween 80.
AB  - Gold nanoparticles conjugated with DNA represent an attractive and alternative
      platform for broad applications in biosensors, medical diagnostic, and biological
      analysis. However, current methods to conjugate DNA to gold nanoparticles are
      time-consuming. In this study, we report a novel approach to rapidly conjugate
      DNA to gold nanoparticles (AuNPs) to form functional DNA/AuNPs in 2-3 h using
      Tween 80 as protective agent. With a fluorescence-based technique, we determine
      that the DNA density on the surface of AuNPs achieves about ~60 strands per
      particles, which is comparable to the loading density in the current methods.
      Moreover, the DNA/AuNPs synthesized by our approach exhibit an excellent
      stability as a function of temperature, pH, and freeze-thaw cycle, and the
      functionality of DNA/AuNPs conjugates is also verified. The work presented here
      has important implications to develop the fast and reproducible synthesis of
      stable DNA-functionalized gold nanoparticles.

PMID- 21961997
TI  - Immune risk phenotype is associated with nosocomial lung infections in elderly in
      patients.
AB  - BACKGROUND: Nosocomial infections are extremely common in the elderly and may be
      related to ageing of the immune system. The Immune Risk Phenotype (IRP), which
      predicts shorter survival in elderly patients, has not been evaluated as a
      possible risk factor for nosocomial infection. Our aim was to assess the
      prevalence of nosocomial infections in elderly in-patients and to investigate
      potential relationships between nosocomial infections and the immunophenotype,
      including IRP parameters. RESULTS: We included 252 consecutive in-patients aged
      70 years or over (mean age, 85 +/- 6.2 years), between 2006 and 2008. Among them,
      97 experienced nosocomial infections, yielding a prevalence rate of 38.5% (95%
      confidence interval, 32.5-44.5). The main infection sites were the respiratory
      tract (21%) and urinary tract (17.1%) When we compared immunological parameters
      including cell counts determined by flow cytometry in the groups with and without
      nosocomial infections, we found that the group with nosocomial infections had
      significantly lower values for the CD4/CD8 ratio and naive CD8 and CD4 T-cell
      counts and higher counts of memory CD8 T-cells with a significant increase in
      CD28-negative CD8-T cells. Neither cytomegalovirus status (positive in 193/246
      patients) nor presence of the IRP was associated with nosocomial infections.
      However, nosocomial pneumonia was significantly more common among IRP-positive
      patients than IRP-negative patients (17/60 versus 28/180; p = 0.036). CONCLUSION:
      Immunological parameters that are easy to determine in everyday practice and
      known to be associated with immune system ageing and shorter survival in the
      elderly are also associated with an elevated risk of nosocomial pneumonia in the
      relatively short term.

PMID- 21961999
TI  - Minimum clinically important difference.

PMID- 21961998
TI  - Immunomodulatory factors in cervicovaginal secretions from pregnant and non
      pregnant women: a cross-sectional study.
AB  - BACKGROUND: Pregnant women are at an increased risk for HIV infection due to
      unknown biological causes. Given the strong effect of sex-hormones on the
      expression of immunomuodulatory factors, the central role of mucosal immunity in
      HIV pathogenesis and the lack of previous studies, we here tested for differences
      in immunomuodulatory factors in cervico-vaginal secretions between pregnant and
      non-pregnant women. METHODS: We compared concentrations of 39 immunomodulatory
      factors in cervicovaginal lavages (CVL) from 21 pregnant women to those of 24 non
      pregnant healthy women from the US. We used Bonferroni correction to correct for
      multiple testing and linear regression modeling to adjust for possible
      confounding by plasma cytokine concentration, cervical ectopy, total protein
      concentration, and other possible confounders. Cervical ectopy was determined by
      planimetry. Concentration of immunomodulatory factors were measured by a
      multiplex assay, protein concentration by the Bradford Method. RESULTS: Twenty
      six (66%) of the 39 measured immunomodulatory factors were detectable in at least
      half of the CVL samples included in the study. Pregnant women had threefold lower
      CVL concentration of CCL22 (geometric mean: 29.6 pg/ml versus 89.7 pg/ml, p =
      0.0011) than non-pregnant women. CVL CCL22 concentration additionally correlated
      negatively with gestational age (Spearman correlation coefficient [RS]: -0.49, p
      = 0.0006). These associations remained significant when corrected for multiple
      testing. CCL22 concentration in CVL was positively correlated with age and
      negatively correlated with time since last coitus and the size of cervical
      ectopy. However, none of these associations could explain the difference of CCL22
      concentration between pregnant and non-pregnant women in this study, which
      remained significant in adjusted analysis. CONCLUSIONS: In this study population,
      pregnancy is associated with reduced concentrations of CCL22 in cervicovaginal
      secretions. The role of CCL22 on HIV transmission should now be investigated in
      prospective studies.

PMID- 21962000
TI  - Oxidative markers in spontaneous intracerebral hemorrhage: leukocyte 8-hydroxy-2'
      deoxyguanosine as an independent predictor of the 30-day outcome.
AB  - OBJECT: Oxidative stress may play a role in spontaneous intracerebral hemorrhage
      (ICH), but data on oxidative burden in cerebral hemorrhage are limited, and it is
      not clear whether oxidative markers add predictive power regarding ICH outcome
      beyond that of traditional factors. The authors therefore examined redox status
      and traditional factors in ICH patients within 3 days of hemorrhage onset to
      delineate redox status in ICH and investigate the predictive value with respect
      to 30-day functional outcome. METHODS: Sixty-four patients with ICH and 114
      controls were prospectively enrolled in this study. Blood samples were collected
      within 3 days of ICH onset and processed for isolation of plasma, erythrocytes,
      and leukocytes. The authors evaluated levels or activities of leukocyte 8-hydroxy
      2'-deoxyguanosine (8-OHdG), erythrocyte glucose-6-phosphate dehydrogenase (G6PD),
      erythrocyte glutathione peroxidase (GPx), plasma malondialdehyde (MDA), vitamin
      E, and vitamin A, as well as traditional factors including the presence of
      hypertension or diabetes mellitus, total cholesterol level, and measures of liver
      function. A general linear model and multivariable logistic regression were used
      for analyses where appropriate. RESULTS: After adjustment for age and sex and
      traditional risk factors, ICH was significantly associated with an increased
      level of 8-OHdG (p < 0.0001), decreased GPx activity (p = 0.0002), and a
      decreased level of vitamin E (p = 0.003). There was no association of ICH risk
      with G6PD activity or MDA or vitamin A level. Considering all the oxidative
      markers and traditional risk factors together, logistic regression showed an
      independent association of ICH with 8-OHdG (OR 2.7, 95% CI 1.7-4.2, p < 0.0001).
      The association between increased 8-OHdG level and lower 30-day Barthel Index was
      also independent of the effects of age, sex, hemorrhage location and size, and
      traditional factors (p = 0.026). Unfavorable outcome (modified Rankin Scale score
      >= 3) at 30 days after ICH onset was not significantly associated with any of the
      examined oxidative markers. CONCLUSIONS: Increased leukocyte 8-OHdG levels, as
      well as decreased GPx activity and vitamin E levels, were found during acute ICH.
      Only 8-OHdG was associated with ICH and the 30-day outcome independently from the
      other oxidative markers and traditional factors. Leukocyte 8-OHdG may add power
      beyond the traditional factors in predicting ICH outcome and thus may be used as
      an independent surrogate for clinical ICH study.

PMID- 21962001
TI  - Hole transfer from single quantum dots.
AB  - Photoinduced hole transfer dynamics from single CdSe/CdS(3ML)/CdZnS(2ML)/ZnS(2ML)
      core/multishell quantum dots (QDs) to phenothiazine (PTZ) molecules were studied
      by single QD fluorescence spectroscopy to investigate the static and dynamic
      heterogeneities of the hole transfer process as well as its effect on the
      blinking dynamics of QDs. Ensemble-averaged transient absorption and fluorescence
      decay measurements show that excitons in QDs dissociate by transferring the
      valence band hole to PTZ with a time constant of 50 ns for the 1:1 PTZ-QD
      complex, and the subsequent charge recombination process (i.e., electron transfer
      from the conduction band of the reduced QD to oxidized PTZ to regenerate the
      complex in the ground state) occurs mainly on the 100 to 1000 ns time scale.
      Single QD-PTZ complexes show pronounced correlated fluctuations of fluorescence
      intensity and lifetime with time. In addition to the dynamic fluctuation, there
      are considerable heterogeneities of average hole transfer rate among different QD
      PTZ complexes. The hole transfer process has little effect on the statistics of
      the off-states, which is often believed to be positively charged QDs with a
      valence band hole. Instead, it increases the probability of weakly emissive or
      "gray" states.

PMID- 21962002
TI  - Comprehensive profiling of radiosensitive human cell lines with DNA damage
      response assays identifies the neutral comet assay as a potential surrogate for
      clonogenic survival.
AB  - In an effort to explore the possible causes of human radiosensitivity and
      identify more rapid assays for cellular radiosensitivity, we interrogated a set
      of assays that evaluate cellular functions involved in recognition and repair of
      DNA double-strand breaks: (1) neutral comet assay, (2) radiation-induced gamma
      H2AX focus formation, (3) the temporal kinetics of structural maintenance of
      chromosomes 1 phosphorylation, (4) intra-S-phase checkpoint integrity, and (5)
      mitochondrial respiration. We characterized a unique panel of 19 "radiosensitive"
      human lymphoblastoid cell lines from individuals with undiagnosed diseases
      suggestive of a DNA repair disorder. Radiosensitivity was defined by reduced
      cellular survival using a clonogenic survival assay. Each assay identified cell
      lines with defects in DNA damage response functions. The highest concordance rate
      observed, 89% (17/19), was between an abnormal neutral comet assay and reduced
      survival by the colony survival assay. Our data also suggested that the neutral
      comet assay would be a more rapid surrogate for analyzing DNA repair/processing
      disorders.

PMID- 21962003
TI  - Radiation attenuates physiological angiogenesis by differential expression of
      VEGF, Ang-1, tie-2 and Ang-2 in rat brain.
AB  - The etiology of radiation-induced cerebrovascular rarefaction remains unknown. In
      the present study, we examined the effect of whole-brain irradiation on
      endothelial cell (EC) proliferation/apoptosis and expression of various
      angiogenic factors in rat brain. F344 * BN rats received either whole-brain
      irradiation (a single dose of 10 Gy gamma rays) or sham irradiation and were
      maintained for 4, 8 and 24 h after irradiation. Double immunofluorescence
      staining was employed to visualize EC proliferation/apoptosis in brain. The mRNA
      and protein expression levels of vascular endothelial growth factor (VEGF),
      angiopoietin-1 (Ang-1), endothelial-specific receptor tyrosine kinase (Tie-2),
      and Ang-2 in brain were determined by real-time RT-PCR and immunofluorescence
      staining. A significant reduction in CD31-immunoreactive cells was detected in
      irradiated rat brains compared with sham-irradiated controls. Whole-brain
      irradiation significantly suppressed EC proliferation and increased EC apoptosis.
      In addition, a significant decrease in mRNA and protein expression of VEGF, Ang-1
      and Tie-2 was observed in irradiated rat brains. In contrast, whole-brain
      irradiation significantly upregulated Ang-2 expression in rat brains. The present
      study provides novel evidence that whole-brain irradiation differentially affects
      mRNA and protein expression of VEGF, Ang-1, Tie-2 and Ang-2. These changes are
      closely associated with decreased EC proliferation and increased EC apoptosis in
      brain.

PMID- 21962005
TI  - MOSFET assessment of radiation dose delivered to mice using the Small Animal
      Radiation Research Platform (SARRP).
AB  - The Small Animal Radiation Research Platform (SARRP) is a novel isocentric
      irradiation system that enables state-of-the-art image-guided radiotherapy
      research to be performed with animal models. This paper reports the results
      obtained from investigations assessing the radiation dose delivered by the SARRP
      to different anatomical target volumes in mice. Surgically implanted metal oxide
      semiconductor field effect transistors (MOSFET) dosimeters were employed for the
      dose assessment. The results reveal differences between the calculated and
      measured dose of -3.5 to 0.5%, -5.2 to -0.7%, -3.9 to 0.5%, -5.9 to 2.5%, -5.5 to
      0.5%, and -4.3 to 0% for the left kidney, liver, pancreas, prostate, left lung,
      and brain, respectively. Overall, the findings show less than 6% difference
      between the delivered and calculated dose, without tissue heterogeneity
      corrections. These results provide a useful assessment of the need for tissue
      heterogeneity corrections in SARRP dose calculations for clinically relevant
      tumor model sites.

PMID- 21962004
TI  - Cancer-prone mice expressing the Ki-rasG12C gene show increased lung
      carcinogenesis after CT screening exposures.
AB  - A >20-fold increase in X-ray computed tomography (CT) use during the last 30
      years has caused considerable concern because of the potential carcinogenic risk
      from these CT exposures. Estimating the carcinogenic risk from high-energy,
      single high-dose exposures obtained from atomic bomb survivors and extrapolating
      these data to multiple low-energy, low-dose CT exposures using the Linear No
      Threshold (LNT) model may not give an accurate assessment of actual cancer risk.
      Recently, the National Lung Cancer Screening Trial (NLST) reported that annual CT
      scans of current and former heavy smokers reduced lung cancer mortality by 20%,
      highlighting the need to better define the carcinogenic risk associated with
      these annual CT screening exposures. In this study, we used the bitransgenic CCSP
      rtTA/Ki-ras mouse model that conditionally expresses the human mutant Ki
      ras(G12C) gene in a doxycycline-inducible and lung-specific manner to measure the
      carcinogenic risk of exposure to multiple whole-body CT doses that approximate
      the annual NLST screening protocol. Irradiated mice expressing the Ki-ras(G12C)
      gene in their lungs had a significant (P = 0.01) 43% increase in the number of
      tumors/mouse (24.1 +/- 1.9) compared to unirradiated mice (16.8 +/- 1.3).
      Irradiated females had significantly (P < 0.005) more excess tumors than
      irradiated males. No tumor size difference or dose response was observed over the
      total dose range of 80-160 mGy for either sex. Irradiated bitransgenic mice that
      did not express the Ki-ras(G12C) gene had a low tumor incidence (<= 0.1/mouse)
      that was not affected by exposure to CT radiation. These results suggest that (i)
      estimating the carcinogenic risk of multiple CT exposures from high-dose
      carcinogenesis data using the LNT model may be inappropriate for current and
      former smokers and (ii) any increased carcinogenic risk after exposure to
      fractionated low-dose CT-radiation may be restricted to only those individuals
      expressing cancer susceptibility genes in their tissues at the time of exposure.

PMID- 21962006
TI  - Exposure to 16O-particle radiation causes aging-like decrements in rats through
      increased oxidative stress, inflammation and loss of autophagy.
AB  - Exposing young rats to particles of high energy and charge (HZE particles), a
      ground-based model for exposure to cosmic rays, enhances indices of oxidative
      stress and inflammation, disrupts the functioning of neuronal communication, and
      alters cognitive behaviors. Even though exposure to HZE particles occurs at low
      fluence rates, the cumulative effects of long-term exposure result in molecular
      changes similar to those seen in aged animals. In the present study, we assessed
      markers of autophagy, a dynamic process for intracellular degradation and
      recycling of toxic proteins and organelles, as well as stress and inflammatory
      responses, in the brains of Sprague-Dawley rats irradiated at 2 months of age
      with 5 and 50 cGy and 1 Gy of ionizing oxygen particles ((16)O) (1000 MeV/n).
      Compared to nonirradiated controls, exposure to (16)O particles significantly
      inhibited autophagy function in the hippocampus as measured by accumulation of
      ubiquitin inclusion bodies such as P62/SQSTM1, autophagosome marker microtubule
      associated protein 1 beta light chain 3 (MAP1B-LC3), beclin1 and proteins such as
      mammalian target of rapamycin (mTOR). The molecular changes measured at short (36
      h) and long (75 days) intervals after (16)O-particle exposure indicate that the
      loss of autophagy function occurred shortly after exposure but was recovered via
      inhibition of mTOR. However, HZE-particle radiation caused significant sustained
      loss of protein kinase C alpha (PKC-alpha), a key G protein modulator involved in
      neuronal survival and functions of neuronal trophic factors. Exposure to (16)O
      particles also caused substantial increases in the levels of nuclear factor kappa
      B (NF-kappaB) and glial fibrillary acidic protein (GFAP), indicating glial cell
      activation 75 days after exposure. This is the first report to show the molecular
      effects of (16)O-particle radiation on oxidative stress, inflammation and loss of
      autophagy in the brain of young rats.

PMID- 21962008
TI  - Predicting solvent stability in aprotic electrolyte Li-air batteries:
      nucleophilic substitution by the superoxide anion radical (O2(*-)).
AB  - There is increasing evidence that cyclic and linear carbonates, commonly used
      solvents in Li ion battery electrolytes, are unstable in the presence of
      superoxide and thus are not suitable for use in rechargeable Li-air batteries
      employing aprotic electrolytes. A detailed understanding of related decomposition
      mechanisms provides an important basis for the selection and design of stable
      electrolyte materials. In this article, we use density functional theory
      calculations with a Poisson-Boltzmann continuum solvent model to investigate the
      reactivity of several classes of aprotic solvents in nucleophilic substitution
      reactions with superoxide. We find that nucleophilic attack by O(2)(*-) at the O
      alkyl carbon is a common mechanism of decomposition of organic carbonates,
      sulfonates, aliphatic carboxylic esters, lactones, phosphinates, phosphonates,
      phosphates, and sulfones. In contrast, nucleophilic reactions of O(2)(*-) with
      phenol esters of carboxylic acids and O-alkyl fluorinated aliphatic lactones
      proceed via attack at the carbonyl carbon. Chemical functionalities stable
      against nucleophilic substitution by superoxide include N-alkyl substituted
      amides, lactams, nitriles, and ethers. The results establish that solvent
      reactivity is strongly related to the basicity of the organic anion displaced in
      the reaction with superoxide. Theoretical calculations are complemented by cyclic
      voltammetry to study the electrochemical reversibility of the O(2)/O(2)(*-)
      couple containing tetrabutylammonium salt and GCMS measurements to monitor
      solvent stability in the presence of KO(2)(*) and a Li salt. These experimental
      methods provide efficient means for qualitatively screening solvent stability in
      Li-air batteries. A clear correlation between the computational and experimental
      results is established. The combination of theoretical and experimental
      techniques provides a powerful means for identifying and designing stable
      solvents for rechargeable Li-air batteries.

PMID- 21962007
TI  - Venous thromboembolism in patients with dermatomyositis and polymyositis.
AB  - OBJECTIVES: To assess the incidence of venous thromboembolic events in
      dermatomyositis and polymyositis patients, and associated factors. METHODS: We
      retrospectively studied a cohort of 123 myositis patients (87 dermatomyositis, 36
      polymyositis) from a single centre and identified cases with deep vein thrombosis
      and/or pulmonary embolism. Type of myositis, association with cancer, presence of
      thrombophilia, disease activity, and intravenous immunoglobulin therapy were
      analysed. Incidence rates were calculated on the basis of time to first venous
      thrombotic event. Patients with less than 12 months' follow-up were excluded.
      RESULTS: Six new first thromboembolic events occurred in 6 of 96 patients studied
      (6.3%), all with dermatomyositis. Median time to development of venous
      thromboembolism was 4.3 months (IQR, 0.8-8.8) after the dermatomyositis
      diagnosis. Venous thromboembolism was significantly associated with intravenous
      immunoglobulin therapy (p<0.05) and older age (p<0.05), but not with cancer. All
      events (100%) occurred during active myositis. The incidence density of venous
      thromboembolism among patients with dermatomyositis according to the first year
      of follow-up was 9.3 per 1000 person-years (95% CI, 3.4 to 20.3). CONCLUSIONS: A
      trend toward venous thromboembolism was detected in patients with
      dermatomyositis.

PMID- 21962009
TI  - Developing public health clinical decision support systems (CDSS) for the
      outpatient community in New York City: our experience.
AB  - BACKGROUND: Developing a clinically relevant set of quality measures that can be
      effectively used by an electronic health record (EHR) is difficult. Whether it is
      achieving internal consensus on relevant priority quality measures, communicating
      to EHR vendors' whose programmers generally lack clinical contextual knowledge,
      or encouraging implementation of EHR that meaningfully impacts health outcomes,
      the path is challenging. However, greater transparency of population health,
      better accountability, and ultimately improved health outcomes is the goal and
      EHRs afford us a realistic chance of reaching it in a scalable way. METHOD: In
      this article, we summarize our experience as a public health government agency
      with developing measures for a public health oriented EHR in New York City in
      partnership with a commercial EHR vendor. RESULTS: From our experience, there are
      six key lessons that we share in this article that we believe will dramatically
      increase the chance of success. First, define the scope and build consensus.
      Second, get support from executive leadership. Third, find an enthusiastic and
      competent software partner. Fourth, implement a transparent operational strategy.
      Fifth, create and test the EHR system with real life scenarios. Last, seek help
      when you need it. CONCLUSIONS: Despite the challenges, we encourage public health
      agencies looking to build a similarly focused public health EHR to create one
      both for improved individual patient as well as the larger population health.

PMID- 21962010
TI  - The ensemble performance index: an improved measure for assessing ensemble pose
      prediction performance.
AB  - We present a theoretical study on the performance of ensemble docking
      methodologies considering multiple protein structures. We perform a theoretical
      analysis of pose prediction experiments which is completely unbiased, as we make
      no assumptions about specific scoring functions, search paradigms, protein
      structures, or ligand data sets. We introduce a novel interpretable measure, the
      ensemble performance index (EPI), for the assessment of scoring performance in
      ensemble docking, which will be applied to simulated and real data sets.

PMID- 21962014
TI  - Nativity is associated with sugar-sweetened beverage and fast-food meal
      consumption among Mexican-origin women in Texas border colonias.
AB  - BACKGROUND: Trends of increasing obesity are especially pronounced among Mexican
      origin women. There is little understanding of dietary patterns among U.S.- and
      Mexico-born Mexican-origin individuals residing in new-destination immigrant
      communities in the United States, especially behaviors related to obesity, such
      as consumption of sugar-sweetened beverages (SSB) and fast-food meals (FFM).
      METHODS: The study used survey data of 599 adult Mexican-origin women from the
      610 women who completed the 2009 Colonia Household and Community Food Resource
      Assessment (C-HCFRA), which was completed in person by trained promotora
      researchers in 44 colonias near the Texas border towns of Progreso and La Feria.
      Data included demographic characteristics (age, education, nativity or country of
      birth, household income, household composition, and employment status), access to
      transportation, self-reported height and weight, food and nutrition assistance
      program participation, and consumption of SSB and FFM. Descriptive statistics
      were calculated by nativity (U.S.-born vs. Mexico-born); multivariable linear
      regression models were estimated for correlates of consumption of SSB and FFM.
      RESULTS: There are three major findings related to nativity. First, U.S.-born
      women consumed more SSB and FFM than Mexican-born counterparts in the same areas
      of colonias. Second, in the combined sample and controlling for other population
      characteristics, being born in Mexico was independently associated with FFM
      (fewer FFM), but not with SSB. Third, in analyses stratified by nativity, FFM and
      SSB were associated with each other among both nativity groups. Among Mexico-born
      women only, age, presence of a child, or being a lone parent was significantly
      associated with SSB; full-time employment, being a lone parent, and SSB
      consumption were each independently associated with increased frequency of FFM.
      CONCLUSIONS: Our analyses revealed differences in prevalence and correlates of
      SSB and FFM based on country of birth. Nativity, as a proxy for acculturation,
      may indicate the extent that immigrants have adopted behaviors from their new
      environment. However, nativity could also indicate limited accessibility to
      resources such as food/nutrition assistance programs, transportation, and proper
      documentation. Additionally, future research should focus on expanding our
      understanding of the meaning of nativity among individuals who share common
      contextual factors, but may have different life course experiences and resources
      needed to transition into a new place. Additional measures should be considered
      such as educational and occupational background, migration history, documentation
      status, and dietary acculturation, which may better explain heterogeneity within
      Hispanic subgroups.

PMID- 21962015
TI  - Scientific Registry of the International Society for Heart and Lung
      Transplantation: introduction to the 2011 annual reports.

PMID- 21962016
TI  - The Registry of the International Society for Heart and Lung Transplantation:
      Twenty-eighth Adult Heart Transplant Report--2011.

PMID- 21962017
TI  - The Registry of the International Society for Heart and Lung Transplantation:
      Fourteenth Pediatric Heart Transplantation Report--2011.

PMID- 21962018
TI  - The Registry of the International Society for Heart and Lung Transplantation:
      Twenty-eighth Adult Lung and Heart-Lung Transplant Report--2011.

PMID- 21962019
TI  - The Registry of the International Society for Heart and Lung Transplantation:
      Fourteenth Pediatric Lung and Heart-Lung Transplantation Report--2011.

PMID- 21962020
TI  - Antioxidant properties of pioglitazone limit nicotinamide adenine dinucleotide
      phosphate hydrogen oxidase and augment superoxide dismutase activity in cardiac
      allotransplantation.
AB  - BACKGROUND: Many non-immunologic factors contribute to the development of cardiac
      allograft vasculopathy (CAV), chief among them being ischemia-reperfusion injury
      associated with oxidative stress. We hypothesized that pioglitazone, a peroxisome
      proliferator-activated receptor (PPAR)-gamma agonist, could attenuate graft
      oxidant stress in cardiac transplantation. METHODS: Experiments were performed
      using a murine heterotopic cardiac allotransplantation model. Pioglitazone was
      administered to recipients once daily, beginning 1 day before transplantation.
      RESULTS: At 4 hours after transplantation, pioglitazone significantly reduced the
      expression of endothelial cell adhesion receptors and infiltration of
      polymorphonuclear leukocytes (PMNs). The anti-oxidant balance in pioglitazone
      treated cardiac allografts was significantly bolstered by reduced nicotinamide
      adenine dinucleotide phosphate hydrogen (NADPH) oxidase (Nox1 and p22(phox) sub
      units) activity and preservation of manganese superoxide dismutase (SOD)
      activity, resulting in the mitigation of oxidative damage at the level of lipids,
      proteins, and DNA. At 7 days after transplantation, PPAR-gamma was significantly
      up-regulated by pioglitazone, but nuclear factor-kappaB and inducible nitric
      oxide synthase were significantly down-regulated. A concomitant reduction of
      inflammatory cytokines and chemokines and graft leukosequestration was noted.
      Pioglitazone consequently prolonged cardiac allograft survival and attenuated CAV
      development. In vitro experiments demonstrated that pioglitazone decreased
      transendothelial PMN migration, NADPH oxidase activity, and loss of SOD activity
      in PMNs and endothelial cells. CONCLUSIONS: Pioglitazone can suppress the
      oxidative stress and damage and can stimulate antioxidant capacity in cardiac
      allografts after transplantation. Mitigation of graft oxidant stress could be an
      important mechanism through which pioglitazone confers benefit after cardiac
      transplantation.

PMID- 21962021
TI  - Early vitamin C and E supplementation and cardiac allograft vasculopathy: 10-year
      follow-up from a randomized, controlled study.

PMID- 21962022
TI  - Synthesis of "two-story" calix[6]aza-cryptands.
AB  - The first four members of a new family of C(3v)-symmetrical "two-story"
      calix[6]aza-cryptands have been synthesized. These large funnel shaped aza
      ligands are formed through introduction of three aromatic arms as spacers onto
      the small rim of a calix[6]arene and subsequently capped with the tripodal aza
      caps tacn [1,3,5-triazacyclononane] or tren [tris(aminoethyl)amine]. A key
      feature for an efficient final 1:1 macrocyclization appears to be an adequate
      geometrical fit between the extended calixarene scaffold and the aza caps.

PMID- 21962024
TI  - An attenuated strain of Bacillus anthracis (CDC 684) has a large chromosomal
      inversion and altered growth kinetics.
AB  - BACKGROUND: An isolate originally labeled Bacillus megaterium CDC 684 was found
      to contain both pXO1 and pXO2, was non-hemolytic, sensitive to gamma-phage, and
      produced both the protective antigen and the poly-D-glutamic acid capsule. These
      phenotypes prompted Ezzell et al., (J. Clin. Microbiol. 28:223) to reclassify
      this isolate to Bacillus anthracis in 1990. RESULTS: We demonstrate that despite
      these B. anthracis features, the isolate is severely attenuated in a guinea pig
      model. This prompted whole genome sequencing and closure. The comparative
      analysis of CDC 684 to other sequenced B. anthracis isolates and further analysis
      reveals: a) CDC 684 is a close relative of a virulent strain, Vollum A0488; b)
      CDC 684 defines a new B. anthracis lineage (at least 51 SNPs) that includes 15
      other isolates; c) the genome of CDC 684 contains a large chromosomal inversion
      that spans 3.3 Mbp; d) this inversion has caused a displacement of the usual
      spatial orientation of the origin of replication (ori) to the termination of
      replication (ter) from 180 degrees  in wild-type B. anthracis to 120 degrees  in
      CDC 684 and e) this isolate also has altered growth kinetics in liquid media.
      CONCLUSIONS: We propose two alternative hypotheses explaining the attenuated
      phenotype of this isolate. Hypothesis 1 suggests that the skewed ori/ter
      relationship in CDC 684 has altered its DNA replication and/or transcriptome
      processes resulting in altered growth kinetics and virulence capacity. Hypothesis
      2 suggests that one or more of the single nucleotide polymorphisms in CDC 684 has
      altered the expression of a regulatory element or other genes necessary for
      virulence.

PMID- 21962023
TI  - Parasite infection is associated with Kaposi's sarcoma associated herpesvirus
      (KSHV) in Ugandan women.
AB  - BACKGROUND: Immune modulation by parasites may influence susceptibility to
      bacteria and viruses. We examined the association between current parasite
      infections, HIV and syphilis (measured in blood or stool samples using standard
      methods) and antibodies against Kaposi's sarcoma herpesvirus (KSHV), measured by
      ELISA, in 1915 stored plasma samples from pregnant women in Entebbe, Uganda.
      RESULTS: Seroprevalence of KSHV was higher in women with malaria parasitaemia
      (73% vs 60% p = 0.01), hookworm (67% vs 56% p = 0.001) and Mansonella perstans
      (69% vs 59% p = 0.05); seroprevalence increased with increasing intensity of
      hookworm infection (p < 0.001[trend]). No associations were found for HIV, five
      other parasites or active syphilis. These effects were not explained by
      socioeconomic status or education. CONCLUSIONS: Specific parasite infections are
      associated with presence of antibodies against KSHV, perhaps mediated via their
      effect on immune function.

PMID- 21962025
TI  - Verbal learning and memory as measured by the Rey-Auditory Verbal Learning Test:
      ADHD with and without learning disabilities.
AB  - The primary purpose of the present study is to examine the effects of attention
      deficits, learning disability, and the combined effects of both on the learning
      and memory processes, as measured by the Rey Auditory Verbal Learning Test
      (AVLT). Thirty children (age range 12-17) diagnosed with attention
      deficit/hyperactivity disorder (ADHD), 18 children (age range 11-17) diagnosed
      with learning disabilities (LD), and 64 children (age range 12-17) diagnosed with
      ADHD as well as with LD, and 28, 18, and 62 matched controls, respectively,
      participated in this study. It was found that the children diagnosed with ADHD
      did not differ in any of the verbal learning and memory measures derived from the
      Rey AVLT. The group with LD was impaired in the overall number of words recalled
      across the learning phase. Performance of the children diagnosed with ADHD +LD
      showed a similar impairment as the group with LD (i.e., overall amount of words
      learned) and, in addition, their retrieval efficiency was also impaired. In
      conclusion, this study indicates that verbal memory is preserved in children with
      ADHD if they have no LD and their intelligence is in the normal range or above.
      LD by itself leads to difficulties in acquisition, but the combination of ADHD+LD
      leads to additional impairment in retrieval processes.

PMID- 21962026
TI  - Melittin adsorption and lipid monolayer disruption at liquid-liquid interfaces.
AB  - Melittin, a membrane-active peptide with antimicrobial activity, was investigated
      at the interface formed between two immiscible electrolyte solutions (ITIES)
      supported on a metallic electrode. Ion-transfer voltammetry showed well-defined
      semi-reversible transfer peaks along with adsorptive peaks. The reversible
      adsorption of melittin at the liquid-liquid interface is qualitatively discussed
      from voltammetric data and experimentally confirmed by real-time image analysis
      of video snapshots. It is also demonstrated that polarization of the water/1,2
      DCE interface results in drastic drop shape variations caused by large variations
      of the interfacial tension. The experimental data also confirmed that maximum
      adsorption occurs near the ion transfer potential. Finally, the interaction of
      melittin with a monolayer of L-alpha-dipalmitoyl phosphatidylcholine (DPPC) was
      also investigated showing that melittin destabilizes the lipidic monolayer
      facilitating its desorption. The non-covalent complex formation between melittin
      and DPPC was confirmed by mass spectrometry.

PMID- 21962027
TI  - Metabolic syndrome in Mediterranean women with polycystic ovary syndrome: when
      and how to predict its onset.
AB  - Polycystic ovary syndrome (PCOS) is associated with the metabolic syndrome
      (MetS). The metabolic disorders are not universal and may vary with race, age and
      phenotype. Our purpose was to determine the clinical and biochemical
      characteristics of Mediterranean PCOS women with MetS, compare them with non-MetS
      PCOS patients, and assess the ability of clinical data and biochemical tests to
      predict these abnormalities within our population. A total of 218 subjects, 196
      PCOS women and 22 controls, undergo a physical examination and laboratory
      evaluation for a diagnosis of MetS. MetS was categorized according to NCEP ATP
      III guidelines. PCOS patients were analyzed separately and compared in three
      subgroups: three or more MetS criteria, two criteria, one or no criteria. The
      overall prevalence of MetS was 21.4%. Women with MetS had higher glucose (G)
      levels than PCOS women with two criteria (5.7 +/- 1.5 vs 5 +/- 0.4, p < 0.05).
      Both groups were comparable for all the other parameters. Waist circumference
      (WC), body mass index (BMI), systolic (SBP) and diastolic blood pressure (DBP),
      bioavailable testosterone (uT), triglycerides (TG) and insulin (I) levels were
      significantly higher and sex hormone-binding globulin (SHBG) levels, high-density
      lipoprotein (HDL), HOMA and QUICKI indexes significantly lower in both groups,
      MetS and patients with two criteria, compared with women with one or no criteria
      and the control group. WC, HDL and TG were the best predictors of PCOS patients
      at risk for MetS. In conclusion, we recommend considering PCOS patients with two
      criteria of MetS as having the same risk as patients with the full syndrome.
      Waist circumference with HDL and triglycerides is an efficient combined test to
      identify PCOS women at risk for metabolic and cardiovascular diseases.

PMID- 21962028
TI  - Fluid-bed coater modifications and study of their influence on the coating
      process of pellets.
AB  - OBJECTIVE: In this study, different modifications of bottom spray fluid-bed
      coater with draft tube inserted were characterized and evaluated. MATERIALS AND
      METHODS: After coating the neutral pellets with polymeric solution comprising
      coloring agent pellet batches were characterized for coating variation, yield and
      degree of agglomeration. RESULTS: Funnel-shaped distribution plate was found to
      improve process yield and decrease the degree of agglomeration at selected values
      of process parameters, whereas coating uniformity was worse in all cases when
      compared to conventional Wurster chamber. Results of the coating chamber with the
      swirl airflow generator indicate more uniform deposition of the coating material
      and in some cases an improved process yield and decreased formation of
      agglomerates when compared to conventional Wurster chamber. In series of
      experiments using Wurster chamber, having tangentially oriented air intake slots,
      which enabled introduction of air above the distribution plate, coating layer was
      more uniformly deposited on the pellet cores and formation of agglomerates was
      lower compared to the results obtained in a conventional Wurster coating chamber.
      CONCLUSION: Modifications of Wurster coating process by introducing swirling air
      motion within the draft tube or by introduction of air above the distribution
      plate have at selected values of process parameters resulted in reduced per
      particle coating variation, degree of agglomeration and improved process yield.

PMID- 21962029
TI  - Diagnosis of latent tuberculosis infection among HIV discordant partners using
      interferon gamma release assays.
AB  - BACKGROUND: There is limited data on the effect of HIV status and CD4 counts on
      performance of Interferon-g Release assays (IGRAs) for diagnosis of latent
      tuberculosis infection (LTBI). METHODS: A cross sectional study was conducted to
      assess the prevalence of and risk factors for a positive diagnostic test for
      LTBI, using tuberculin skin test (TST) and IGRAs among HIV-discordant couples in
      Zambia. RESULTS: A total of 596 subjects (298 couples) were enrolled. Median CD4
      count among HIV positive persons was 388 cells/MUl, (range 51-1330). HIV negative
      persons were more likely than their HIV positive partner, to have a positive
      diagnostic test for LTBI with TST (203 vs 128), QFT (171 vs 109) and TSPOT (156
      vs. 109). On multivariate analysis, HIV negative status was an independent
      predictor for a positive QFT (OR = 2.22, 95% CI 1.42- 3.46) and TSPOT (OR = 1.79,
      95% CI 1.16-2.77). Among HIV positive subjects a CD4 count >= 388 cells/MUl was
      associated with a positive TST (OR = 1.76 95% CI 1.10-2.82) and QFT (OR = 1.71
      95% CI 1.06-2.77) but not TSPOT (OR = 1.20 95% CI 0.74-1.94). CONCLUSIONS:
      Persons with HIV had significantly fewer positive diagnostic tests for LTBI with
      TST, QFT and TSPOT. Persons with a CD4 count < 388 cells/MUl were less likely to
      have a positive TST or QFT, but not less likely to have a positive TSPOT. TSPOT
      may perform better than TST or QFT in HIV positive individuals.

PMID- 21962030
TI  - Research productivity in neurosurgery: trends in globalization, scientific focus,
      and funding.
AB  - OBJECT: While research is important for the survival, growth, and expansion of
      neurosurgery, little work has been done to quantify the status and trends of
      neurosurgical publications. The purpose of this bibliometric study was to
      quantitatively analyze trends in neurosurgical publications, including changes in
      worldwide productivity, study methodology, subspecialty topic, and funding.
      METHODS: This was a retrospective bibliometric study using MEDLINE to record all
      publications between 1996 and 2009 by first authors affiliated with neurosurgical
      departments. Country of origin, MEDLINE-defined methodology, study topic, and
      funding sources (for US articles) were recorded. Linear regression was used to
      derive growth rates. RESULTS: Total articles numbered 53,425 during the study
      period, with leading global contributors including the US with 16,943 articles
      (31.7%) and Japan with 10,802 articles (20.2%). Countries demonstrating rapid
      growth in productivity included China (121.9 +/- 9.98%/year, p < 0.001), South
      Korea (50.5 +/- 4.7%/year, p < 0.001), India (19.4 +/- 1.8%/year, p < 0.001), and
      Turkey (25.3 +/- 2.8%/year, p < 0.001). While general research articles, case
      reports, and review articles have shown steady growth since 1996, clinical trials
      and randomized controlled trials have declined to 2004 levels. The greatest
      overall subspecialty growth was seen in spine surgery. Regarding funding,
      relative contribution of National Institutes of Health (NIH)-funded publications
      decreased from 30.2% (290 of 959) to 22.5% (356 of 1229) between 1996 and 2009.
      CONCLUSIONS: Neurosurgical publications demonstrate continued increases in
      productivity as well as in global expansion, although US contributions remain
      dominant. Two challenges that the neurosurgical community is facing include the
      preponderance of case reports and review articles and the relative decline in NIH
      funding for US neurosurgical publications, as productivity has outpaced
      government financial support.

PMID- 21962031
TI  - Attributing the burden of cancer at work: three areas of concern when examining
      the example of shift-work.
AB  - This commentary intends to instigate discussions about epidemiologic estimates
      and their interpretation of attributable fractions (AFs) and the burden of
      disease (BOD) of cancers due to factors at workplaces. By examining recent work
      that aims to estimate the number of cancers attributable to shift-work in
      Britain, we suggest that (i) causal, (ii) practical and (iii) methodological
      areas of concern may deter us from attributable caseload estimations of cancers
      at this point in time. Regarding (i), such calculations may have to be avoided as
      long as we lack established causality between shift-work and the development of
      internal cancers. Regarding (ii), such calculations may have to be avoided as
      long as we can neither abandon shift-work nor identify personnel that may be
      unaffected by shift-work factors. Regarding (iii), there are at least four
      methodological pitfalls which are likely to make AF calculations uninterpretable
      at this stage. The four pitfalls are: (1) The use of Levin's 1953 formula in case
      of adjusted relative risks; (2) The use of broad definitions of exposure in
      calculations of AFs; (3) The non-additivity of AFs across different levels of
      exposure and covariables; (4) The fact that excess mortality counts are
      misleading due to the fact that a human being dies exactly once - a death may
      occur earlier or later, but a death cannot occur more than once nor can it be
      avoided altogether for any given individual. Overall, causal, practical and
      methodological areas of concern should be diligently considered when performing
      and interpreting AF or BOD computations which - at least at the present time -
      may not be defensible.

PMID- 21962032
TI  - Letter to the editor: cervical stability.

PMID- 21962033
TI  - Prospective assessment of patient morbidity from prone sacral positioning.
AB  - OBJECT: Sacrectomy positioning must balance surgical exposure, localization,
      associated operative procedures, and patient safety. Poor positioning may
      increase hemorrhage, risk of blindness, and skin breakdown. METHODS: The authors
      prospectively identified positioning-related morbidity in 17 patients undergoing
      19 prone sacral procedures from September 2008 to August 2009 following
      institution of a standardized positioning protocol. Key elements include skull
      traction/head suspension, an open radiolucent frame, and wide draping for
      associated closure and reconstructive procedures. RESULTS: Tumors included 5
      chordomas, 4 high-grade sarcomas, 1 chondrosarcoma, 2 presacral extradural
      myxopapillary ependymomas, and 5 others. Mean patient age was 49.9 years (range
      17-74 years); mean body mass index was 27.6 kg/m(2) (range 19.3-43.9 kg/m(2)).
      Mean preoperative Braden skin integrity score was 21.1 (range 17-23). Average
      operative time was 501 minutes (range 158-1136 minutes). Prone surgery was a part
      of staged anterior/posterior resections in 8 patients. Localization was conducted
      using fluoroscopy in 13 patients and intraoperative CT in 4 patients. All imaging
      studies were successful. One patient developed a transient ulnar nerve palsy
      attributed to positioning. Three patients (two of whom were morbidly obese)
      developed Stage I pressure injuries to the chest and another developed Stage II
      pressure injury following a 1136-minute procedure. Morbidity was only observed in
      patients with morbid obesity or with procedures lasting in excess of 10 hours.
      CONCLUSIONS: A positioning protocol using head suspension on an open radiolucent
      frame facilitates oncological sacral surgery with reasonable patient morbidity.
      Morbid obesity and procedure times in excess of 10 hours are risk factors for
      positioning-related complications. To the authors' knowledge, this is the first
      report of surgical positioning morbidity in this patient population.

PMID- 21962034
TI  - Determination of minimum clinically important difference in pain, disability, and
      quality of life after extension of fusion for adjacent-segment disease.
AB  - OBJECT: Spinal surgical outcome studies rely on patient-reported outcome (PRO)
      measurements to assess treatment effect. A shortcoming of these questionnaires is
      that the extent of improvement in their numerical scores lack a direct clinical
      meaning. As a result, the concept of minimum clinical important difference (MCID)
      has been used to measure the critical threshold needed to achieve clinically
      relevant treatment effectiveness. As utilization of spinal fusion has increased
      over the past decade, so has the incidence of adjacent-segment degeneration
      following index lumbar fusion, which commonly requires revision laminectomy and
      extension of fusion. The MCID remains uninvestigated for any PROs in the setting
      of revision lumbar surgery for adjacent-segment disease (ASD). METHODS: In 50
      consecutive patients undergoing revision surgery for ASD-associated back and leg
      pain, PRO measures of back and leg pain on a visual analog scale (BP-VAS and LP
      VAS, respectively), Oswestry Disability Index (ODI), 12-Item Short Form Health
      Survey Physical and Mental Component Summaries (SF-12 PCS and MCS, respectively),
      and EuroQol-5D health survey (EQ-5D) were assessed preoperatively and 2 years
      postoperatively. The following 4 well-established anchor-based MCID calculation
      methods were used to calculate MCID: average change; minimum detectable change
      (MDC); change difference; and receiver operating characteristic curve (ROC)
      analysis for the following 2 separate anchors: health transition item (HTI) of
      the SF-36 and satisfaction index. RESULTS: All patients were available for 2-year
      PRO assessment. Two years after surgery, a statistically significant improvement
      was observed for all PROs (mean changes: BP-VAS score [4.80 +/- 3.25], LP-VAS
      score [3.28 +/- 3.25], ODI [10.24 +/- 13.49], SF-12 PCS [8.69 +/- 12.55] and MCS
      [8.49 +/- 11.45] scores, and EQ-5D [0.38 +/- 0.45]; all p < 0.001). The 4 MCID
      calculation methods generated a range of MCID values for each of the PROs (BP-VAS
      score, 2.3-6.5; LP-VAS score, 1.7-4.3; ODI, 6.8-16.9; SF-12 PCS, 6.1-12.6; SF-12
      MCS, 2.4-10.8; and EQ-5D, 0.27-0.54). The area under the ROC curve was
      consistently greater for the HTI anchor than the satisfaction anchor, suggesting
      this as a more accurate anchor for MCID. CONCLUSIONS: Adjacent-segment disease
      revision surgery-specific MCID is highly variable based on calculation technique.
      The MDC approach with HTI anchor appears to be most appropriate for calculation
      of MCID after revision lumbar fusion for ASD because it provided a threshold
      above the 95% CI of the unimproved cohort (greater than the measurement error),
      was closest to the mean change score reported by improved and satisfied patients,
      and was not significantly affected by choice of anchor. Based on this method,
      MCID following ASD revision lumbar surgery is 3.8 points for BP-VAS score, 2.4
      points for LP-VAS score, 6.8 points for ODI, 8.8 points for SF-12 PCS, 9.3 points
      for SF-12 MCS, and 0.35 quality-adjusted life-years for EQ-5D.

PMID- 21962035
TI  - Raman characterization of ABA- and ABC-stacked trilayer graphene.
AB  - Bernal (ABA stacking order) and rhombohedral (ABC) trilayer graphene (3LG) are
      characterized by Raman spectroscopy. From a systematic experimental and
      theoretical analysis of the Raman modes in both of these 3LGs, we show that the G
      band, G' (2D) band, and the intermediate-frequency combination modes of 3LGs are
      sensitive to the stacking order of 3LG. The phonon wavevector q, that gives the
      double resonance Raman spectra is larger in ABC than ABA, which is the reason why
      we get the different Raman frequencies and their spectral widths for ABA and ABC
      3LG. The weak electron-phonon interaction in ABC-stacked 3LG and the localized
      strain at the boundary between ABC- and ABA-stacked domains are clearly reflected
      by the softening of the G mode and the G' mode, respectively.

PMID- 21962036
TI  - Progression of articular and extraarticular damage in oligoarticular juvenile
      idiopathic arthritis.
AB  - OBJECTIVES: Evaluate damage in oligoarticular JIA, estimating its frequency,
      risks and probability over time. METHODS: A cross-sectional and retrospective
      analysis of Juvenile Arthritis Damage Index (JADI) scoring, with both articular
      and extraarticular components, active joint count, disability index by CHAQ and
      Steinbrocker class, physician's global assessment, child's pain and overall well
      being visual analogue scale (VAS), was conducted in patients with oligoarticular
      JIA. Damage risk factors were estimated by univariate analysis and by generalised
      linear model. The probability of damage over time was estimated by survival
      analysis and damage progression rates were calculated by hazard function.
      RESULTS: Seventy-five JIA cases were assessed, 89.3% persistent and 10.7%
      extended oligoarthritis, with median follow-up duration 1.7 years (IQR 1.3-3.1).
      Damage occurred in 38.7%. JADI-A correlated moderately only with the number of
      limited joints (rs= 0.50, p<0.0001). Female sex (OR 3.5, 95% CI 1.0-11.6), DMARD
      use (OR 3.9, 95%CI 1.0-15.0) and knee involvement (OR 4.2, 95%CI 1.3-13.5) were
      significantly associated with joint damage, whereas only joint steroid injection
      was associated with extraarticular damage (OR 5.9, 95% CI 1.8-19.3). Damage
      probability at 5 years was 50% for JADI-A, and 57% for JADI-E. Calculated hazard
      rates each year were 16.1% and 16.3%, for JADI-A and JADI-E, respectively.
      CONCLUSIONS: Sex, DMARD use and knee involvement were associated with joint
      damage, whereas only joint steroid injection was associated with extraarticular
      damage, which progressed at stable rates over ten years.

PMID- 21962037
TI  - Effective fragment potential study of the influence of hydration on the
      vibrational spectrum of glucose.
AB  - The standard agent glucose has been the subject of numerous experimental and
      theoretical studies, especially in the aqueous environments which are present in
      most biochemical processes. The impact of the solvation process on the
      vibrational spectra of glucose in the mid-infrared region is investigated in this
      work. The computational study focused both on the variation of the number of
      surrounding water molecules from 0 to 229 and on the number of single spectra
      included in the iterative averaging process. The calculations consisted of a
      combination of force field methods for the sampling of the configuration space
      and density functional theory for further geometry optimizations. Effective
      fragment potentials (EFPs) were employed for the description of the solvent as a
      compromise between accuracy and computational complexity. A correlation between
      the experimental data and the number of surrounding water molecules could not be
      observed for an averaging over a small set of computed single spectra. The
      inclusion of an additionial polarizable continuum model (PCM) also showed no
      further impact. However, an increase in the number of underlying single spectra
      in the averaging process increased the correlation between simulations and the
      experiment substantially. Especially for 18 explicit EFP water molecules, an
      inclusion of 80 single spectra delivered a Pearson's correlation coefficient r ~
      0.94.

PMID- 21962045
TI  - A comparison of the incidence and understanding of altitude illness between
      porters and trekkers in the Solu Khumbu Region of Nepal.
AB  - OBJECTIVE: Altitude illness can occur in anyone who ascends to high altitude.
      Better understanding of altitude illness is associated with a lower incidence of
      acute mountain sickness (AMS). The purpose of this study is to compare, for the
      first time, the incidence and understanding of altitude illness between foreign
      trekkers and indigenous porters in Nepal. METHODS: Interviews and questionnaires
      were completed at the International Porter Protection Group Rescue Post at
      Machermo (4470 m). Participants completed the Lake Louise acute mountain sickness
      self-assessment questionnaire. They were also asked about their actions in
      response to high altitude illness scenarios as well as their perception of the
      vulnerability of porters vs trekkers to altitude illness. Ascent profile, age,
      gender, ethnic origin, and altitude of home residence were also obtained.
      RESULTS: Trekkers (n=131) had a significantly higher incidence of AMS (21% vs 8%)
      than porters (n=92; P < .02). Lowland porters (whose home villages were below
      3050 m, n=61) had a numerically higher, though not significantly different,
      incidence of AMS (10% vs 3%) compared to highland porters (n=31). The majority of
      trekkers and porters recognized the symptoms of altitude illness and the most
      appropriate action to be taken. Despite the lower incidence of AMS in porters,
      around half felt that they were at greater risk than trekkers. CONCLUSIONS:
      Porters had a lower incidence of AMS, which may be attributable to repeated
      ascents through the trekking season, or differences in reporting symptoms. Both
      trekkers and porters demonstrated appropriate knowledge of actions to be taken in
      response to altitude illness.

PMID- 21962038
TI  - Metabolically healthy and unhealthy obesity phenotypes in the general population:
      the FIN-D2D Survey.
AB  - BACKGROUND: The aim of this work was to examine the prevalence of different
      metabolical phenotypes of obesity, and to analyze, by using different risk
      scores, how the metabolic syndrome (MetS) definition discriminates between
      unhealthy and healthy metabolic phenotypes in different obesity classes. METHODS:
      The Finnish type 2 diabetes (FIN-D2D) survey, a part of the larger implementation
      study, was carried out in 2007. The present cross-sectional analysis comprises
      2,849 individuals aged 45-74 years. The MetS was defined with the new
      Harmonization definition. Cardiovascular risk was estimated with the Framingham
      and SCORE risk scores. Diabetes risk was assessed with the FINDRISK score. Non
      alcoholic fatty liver disease (NAFLD) was estimated with the NAFLD score.
      Participants with and without MetS were classified in different weight categories
      and analysis of regression models were used to test the linear trend between body
      mass index (BMI) and various characteristics in individuals with and without
      MetS; and interaction between BMI and MetS. RESULTS: A metabolically healthy but
      obese phenotype was observed in 9.2% of obese men and in 16.4% of obese women.
      The MetS-BMI interaction was significant for fasting glucose, 2-hour plasma
      glucose, fasting plasma insulin and insulin resistance (HOMA-IR)(p < 0.001 for
      all). The prevalence of total diabetes (detected prior to or during survey) was
      37.0% in obese individuals with MetS and 4.3% in obese individuals without MetS
      (p < 0.001). MetS-BMI interaction was significant (p < 0.001) also for the
      Framingham 10 year CVD risk score, NAFLD score and estimated liver fat %,
      indicating greater effect of increasing BMI in participants with MetS compared to
      participants without MetS. The metabolically healthy but obese individuals had
      lower 2-hour postload glucose levels (p = 0.0030), lower NAFLD scores (p < 0.001)
      and lower CVD risk scores (Framingham, p < 0.001; SCORE, p = 0.002) than normal
      weight individuals with MetS. CONCLUSIONS: Undetected Type 2 diabetes was more
      prevalent among those with MetS irrespective of the BMI class and increasing BMI
      had a significantly greater effect on estimates of liver fat and future CVD risk
      among those with MetS compared with participants without MetS. A healthy obese
      phenotype was associated with a better metabolic profile than observed in normal
      weight individuals with MetS.

PMID- 21962046
TI  - Effects of sleep or food deprivation during civilian survival training on
      cognition, blood glucose and 3-OH-butyrate.
AB  - OBJECTIVES: The study was designed to compare effects of food deprivation (FD)
      and sleep deprivation (SD) on cognition during survival training. METHODS: In a
      cross-over design (n=12), the effects of FD (up to 66 hours followed by 500 kcal
      intake over 24 hours) and SD (up to 50 hours) on cognitive variables, blood
      glucose, and 3-OH-butyrate were studied. RESULTS: Food deprivation and SD
      impaired attention-dependent tasks. The FD impairment of simple reaction time was
      independent of blood glucose levels, which were normalized by a 500 kcal intake
      over 24 hours while the reaction time was not. Sleep deprivation and FD impaired
      maze-solving performance on all variables except rule breaks, which were
      significantly occurring after 50 hours of SD. Delayed word recall was impaired by
      SD for 50 hours. On the Balloon Analogue Risk Task, SD was associated with
      reduced risk-taking. In a gambling task, both SD for 50 hours and FD for 66 hours
      were associated with a tendency to make early choices when presented with
      consecutive choices, but the risk-taking was not affected. CONCLUSIONS: Sleep
      deprivation has multiple cognitive effects, including attention, memory, visual
      spatial ability, and risk-taking. Food deprivation had no affect on risk-taking,
      while the other tasks were affected in a way similar to SD but were less
      pronounced. The FD effects on cognition did not appear to depend on blood sugar
      levels. The need to sleep should be prioritized in survival situations to avoid
      cognitive impairment.

PMID- 21962047
TI  - Injuries in mountain bike racing: frequency of injuries in endurance versus cross
      country mountain bike races.
AB  - OBJECTIVE: To determine the frequency of injuries requiring medical attention
      among mountain bike racers at endurance races (6 hours or greater in duration)
      versus traditional cross country races (less than 6 hours duration) and to
      determine the medical support available at races. METHODS: A survey was developed
      to determine participants' experience level, previous injuries, and demographic
      information. An additional survey was completed by injured riders to determine
      injuries and treatment received. The number of medical providers, their level of
      training, and the supplies available was determined. RESULTS: The endurance
      riders had more years of mountain biking experience, averaged more hours of
      riding per week, and had fewer injuries requiring medical attention in the past
      year than the riders in the races. Of the cross-country riders, 7.2% were injured
      during the race, and 4.7% of endurance racers were injured. There was no
      increased risk of being injured in a race over an endurance race (odds ratio 1.6,
      95% CI [0.50, 2.92]). Lacerations and abrasions were the most common injuries in
      both events. Head injuries, eye injuries, and blisters were only reported in the
      endurance events. Endurance events were more likely to have medical assistance
      available. CONCLUSION: There was a greater percentage of riders reporting
      injuries in the cross-country races. It is possible that many of the endurance
      racers did not report injuries, continuing to ride or taking care of their own
      injuries quickly. Both events tended to have similar types of injuries and,
      therefore, both events most likely need similar medical support.

PMID- 21962048
TI  - Snowboarding injuries in Australia: investigating risk factors in wrist fractures
      to enhance injury prevention strategies.
AB  - OBJECTIVE: To investigate risk factors associated with wrist fractures in
      snowboarders to inform future snowsport safety strategies. METHODS: A prospective
      case-control study using a nonprobability convenience sample was conducted with
      data collected via a respondent-completed questionnaire. Subjects consisted of
      snowboarders with a snowboard-related injury who presented to one of 10 medical
      centers and physiotherapy clinics in resort medical centers and gateway
      communities across the Australian snowsport season in 2007. Those presenting with
      injuries other than wrist fractures acted as the control. RESULTS: The 611
      respondents reported 802 injuries (61.3% were males and 51.5% were aged 16-25
      years). Protective equipment was worn by 57.0% of respondents. The main reason
      for not wearing a wrist guard was that they did not see the need; of these, 12.9%
      experienced a wrist fracture. Most injuries occurred on-piste, in a terrain park,
      or in a lesson. The main mechanism of injury was falling. The major risk factors
      for wrist fractures were being less than 16 years of age (OR 3.97, CI 2.54-6.22),
      being in the alpine area for a holiday (OR 2.77, CI 1.47-5.21), and being a first
      day snowboard participant (OR 2.02, CI 1.15-3.64). A direct logistic regression
      indicated that 3 variables had a statistically significant contribution to the
      model (being less than 16 years old, being on holidays in the region, and not
      wearing a wrist guard). CONCLUSIONS: The key risk factors in this Australian
      study reflect other international studies, providing a clear market segment for
      targeted snowsport safety messages: those less than 16 years old, visitors to the
      alpine regions, and those not wearing wrist guards.

PMID- 21962049
TI  - Physiological adaptation of a mature adult walking the Alps.
AB  - Research on endurance locomotion has mainly focused on elite athletes rather than
      common middle-aged subjects. Our report describes the physiological and
      hematological adaptation of a healthy, active 62-year-old man who trekked alone
      along a 1300 km/3 month course of Alpine paths (Via Alpina). The following
      procedures were conducted: pre- and post-trekking and fortnightly field
      anthropometry (total and lean body mass), functional tests (isometric maximal
      voluntary force, spontaneous walking speed, relative metabolic cost, and peak
      oxygen consumption) and clinical chemistry/hematological measurements with
      laboratory instruments; daily self-administered effort measurements using
      portable devices along the route (walked distance, ascent, descent, time,
      metabolic consumption, and cost). Despite the tough trekking route, the subject
      completed the trek without any worsening of his performance, or any significant
      health or functional problems. In addition, his peak oxygen consumption increased
      by 13.2%. His successful adaptation may be attributed to his constant, repeated
      middle-intensity and extensive exercise and lengthy exposure to high altitude.
      The clinical chemistry/hematological measurements documented his physiological
      adaptation. In conclusion, we show how an active, middle-aged man can
      successfully face endurance trekking, not only without any harm to his health or
      functions but also with an increase in his capacity to support specific effort.

PMID- 21962050
TI  - Management of a wild boar wound: a case report.
AB  - Injuries caused by wild boar attacks are rare. A 34-year-old male shepherd
      sustained injuries caused by a wild boar attack, and was brought to our emergency
      department. The patient had 2 skin and deep tissue lacerations on the posterior
      aspect of his thigh. Herein, we discuss the clinical management of a wild boar
      bite wound with a review of the literature.

PMID- 21962051
TI  - Case report of probable desert black snake envenomation in 22-year-old male
      causing profound weakness and respiratory distress.
AB  - We describe a case of a 22-year-old male who presented to our facility 1 hour
      after a snake bite, which he identified as the desert black snake. He presented
      with severe weakness and respiratory distress. He was treated with polyvalent
      antivenom and observed in the Intensive Care Unit (ICU) with resolution of his
      respiratory symptoms. He developed paresthesias locally around his wound and
      later complained of diplopia. Two days later, he had total resolution of his
      symptoms. This is one of the only clinical reports of neurotoxic effects after
      Walterinnesia morgani envenomation.

PMID- 21962052
TI  - Effects of oxygen supplementation on acute mountain sickness symptoms and
      functional capacity during a 2-kilometer walk test on Chajnantor plateau (5050
      meters, Northern Chile).
AB  - OBJECTIVE: The aim of this study was to test the hypothesis that administration
      of low-flow oxygen will improve physical performance in subjects unacclimatized
      to altitude. We evaluated the effects of oxygen supplementation on functional
      capacity and acute mountain sickness (AMS) symptoms in young, healthy male and
      female subjects who performed a 2-km fast walk test following rapid ascent to the
      Chajnantor plateau (5050 m above sea level) in Northern Chile. METHODS: The
      participants were randomly distributed into 2 groups according to oxygen
      supplementation levels: 1 or 3 L O(2) . min(-1). Within each group, males and
      females were evaluated separately. A preliminary walk test was carried out at sea
      level on a 100-m long, flat track with 10 U-turns. For the first walk at
      altitude, subjects carried the supplementary oxygen system but did not breathe
      the oxygen. Subjects received oxygen through a facemask the following day during
      the second test. The nights prior to altitude tests were spent at 2400 m in San
      Pedro de Atacama. RESULTS: Supplementary oxygen administration during a 2-km walk
      test significantly improved walking times at 5050 m. We also observed a
      significant improvement in AMS symptoms. As expected, however, performance was
      poorer at altitude compared to test values at sea level, despite supplementary
      oxygen administration. CONCLUSIONS: Our findings demonstrate the beneficial
      effects of supplementary oxygen administration on physical capacity, reducing the
      incidence of AMS and, thus, improving health and safety conditions for high
      altitude workers following rapid ascent, when adequate acclimatization is not
      possible.

PMID- 21962053
TI  - Goddess mother.

PMID- 21962054
TI  - In response to "Attack upon a bather by a swordfish".

PMID- 21962056
TI  - Formation of 1:2 host-guest complexes based on triptycene-derived macrotricycle
      and paraquat derivatives: anion-pi interactions between PF6(-) and bipyridinium
      rings in the solid state.
AB  - A triptycene-derived macrotricyclic host containing two dibenzo-[30]-crown-10
      moieties forms stable 1:2 host-guest complexes with paraquat derivatives in both
      solution and the solid state, in which anion-pi interactions between PF(6)(-) and
      the bipyridinium rings play an important role. Moreover, it was found that
      binding and release of the guest molecules in the complexes could be easily
      controlled by the addition and removal of potassium ions.

PMID- 21962058
TI  - 100th anniversary of the Anglo-American Pikes Peak Expedition.

PMID- 21962057
TI  - How neurons migrate: a dynamic in-silico model of neuronal migration in the
      developing cortex.
AB  - BACKGROUND: Neuronal migration, the process by which neurons migrate from their
      place of origin to their final position in the brain, is a central process for
      normal brain development and function. Advances in experimental techniques have
      revealed much about many of the molecular components involved in this process.
      Notwithstanding these advances, how the molecular machinery works together to
      govern the migration process has yet to be fully understood. Here we present a
      computational model of neuronal migration, in which four key molecular entities,
      Lis1, DCX, Reelin and GABA, form a molecular program that mediates the migration
      process. RESULTS: The model simulated the dynamic migration process, consistent
      with in-vivo observations of morphological, cellular and population-level
      phenomena. Specifically, the model reproduced migration phases, cellular dynamics
      and population distributions that concur with experimental observations in normal
      neuronal development. We tested the model under reduced activity of Lis1 and DCX
      and found an aberrant development similar to observations in Lis1 and DCX
      silencing expression experiments. Analysis of the model gave rise to unforeseen
      insights that could guide future experimental study. Specifically: (1) the model
      revealed the possibility that under conditions of Lis1 reduced expression,
      neurons experience an oscillatory neuron-glial association prior to the
      multipolar stage; and (2) we hypothesized that observed morphology variations in
      rats and mice may be explained by a single difference in the way that Lis1 and
      DCX stimulate bipolar motility. From this we make the following predictions: (1)
      under reduced Lis1 and enhanced DCX expression, we predict a reduced bipolar
      migration in rats, and (2) under enhanced DCX expression in mice we predict a
      normal or a higher bipolar migration. CONCLUSIONS: We present here a system-wide
      computational model of neuronal migration that integrates theory and data within
      a precise, testable framework. Our model accounts for a range of observable
      behaviors and affords a computational framework to study aspects of neuronal
      migration as a complex process that is driven by a relatively simple molecular
      program. Analysis of the model generated new hypotheses and yet unobserved
      phenomena that may guide future experimental studies. This paper thus reports a
      first step toward a comprehensive in-silico model of neuronal migration.

PMID- 21962062
TI  - Prehospital resuscitation of the buried avalanche victim.
AB  - In North America and Europe, approximately 150 people die of avalanches per year,
      and fatalities are presumed to be many times higher in developing countries. Four
      factors are decisive for survival: grade of burial, duration of burial, presence
      of an air pocket and a free airway, and severity of trauma. According to Swiss
      data, the overall mortality rate with avalanche burial is 23%, but it largely
      depends on the grade of burial. While the mortality rate is 52.4% in completely
      buried (head below the snow) victims in the Swiss population, it is only 4.2% in
      partially buried (head free) victims. Additionally, survival in completely buried
      victims drops to 30% within the first 35 min, initially due to death from lethal
      trauma, followed by asphyxia in 20-35 min. Thereafter, survival decreases more
      gradually and victims who are not fatally injured and are able to breath under
      the snow slowly succumb to hypoxia, hypercapnia, and hypothermia. In the absence
      of fatal injuries, rescue strategies depend on the duration of burial and the
      victim's core temperature. With a burial time<35 min, survival depends on
      preventing asphyxia by rapid extrication, adequate airway management, and
      cardiopulmonary resuscitation. With a burial time>35 min, tackling hypothermia is
      of utmost importance. Therefore, gentle extrication and continuous core
      temperature and electrocardiogram monitoring are recommended. Pulseless victims
      with a patent airway and a core temperature<32 degrees C should receive
      uninterrupted cardiopulmonary resuscitation and be transported to a hospital with
      extracorporeal rewarming facilities.

PMID- 21962063
TI  - Sildenafil citrate for the prevention of high altitude hypoxic pulmonary
      hypertension: double blind, randomized, placebo-controlled trial.
AB  - Exaggerated hypoxic pulmonary vasoconstriction is a key factor in the development
      of high altitude pulmonary edema (HAPE). Due to its effectiveness as a pulmonary
      vasodilator, sildenafil has been proposed as a prophylactic agent against HAPE.
      By conducting a parallel-group double blind, randomized, placebo-controlled
      trial, we investigated the effect of chronic sildenafil administration on
      pulmonary artery systolic pressure (PASP) and symptoms of acute mountain sickness
      (AMS) during acclimatization to high altitude. Sixty-two healthy lowland
      volunteers (36 male; median age 21 years, range 18 to 31) on the Apex 2 research
      expedition were flown to La Paz, Bolivia (3650 m), and after 4-5 days
      acclimatization ascended over 90 min to 5200 m. The treatment group (n=20)
      received 50 mg sildenafil citrate three times daily. PASP was recorded by
      echocardiography at sea level and within 6 h, 3 days, and 1 week at 5200 m. AMS
      was assessed daily using the Lake Louise Consensus symptom score. On intention-to
      treat analysis, there was no significant difference in PASP at 5200 m between
      sildenafil and placebo groups. Median AMS score on Day 2 at 5200 m was
      significantly higher in the sildenafil group (placebo 4.0, sildenafil 6.5;
      p=0.004) but there was no difference in prevalence of AMS between groups.
      Sildenafil administration did not affect PASP in healthy lowland subjects at 5200
      m but AMS was significantly more severe on Day 2 at 5200 m with sildenafil. Our
      data do not support routine prophylactic use of sildenafil to reduce PASP at high
      altitude in healthy subjects with no history of HAPE. TRIALS REGISTRATION NUMBER:
      NCT00627965.

PMID- 21962064
TI  - Sildenafil has little influence on cardiovascular hemodynamics or 6-km time trial
      performance in trained men and women at simulated high altitude.
AB  - Sildenafil improves maximal exercise capacity at high altitudes (~4350-5800 m) by
      reducing pulmonary arterial pressure and enhancing oxygen delivery, but the
      effects on exercise performance at less severe altitudes are less clear. PURPOSE:
      To determine the effects of sildenafil on cardiovascular hemodynamics (heart
      rate, stroke volume, and cardiac output), arterial oxygen saturation (SaO2), and
      6-km time-trial performance of endurance-trained men and women at a simulated
      altitude of ~3900 m. METHODS: Twenty men and 15 women, endurance-trained,
      completed one experimental exercise trial (30 min at 55% of altitude-specific
      capacity +6-km time trial) at sea level (SL) and two trials at simulated high
      altitude (HA) while breathing hypoxic gas (12.8% FIo2) after ingestion of either
      placebo or 50 mg sildenafil in double-blind, randomized, and counterbalanced
      fashion. RESULTS: Maximal exercise capacity and SaO2 were significantly reduced
      at HA compared to SL (18%-23%), but sildenafil did not significantly improve
      cardiovascular hemodynamics or time-trial performance in either men or women
      compared to placebo and only improved SaO2 in women (4%). One male subject (5% of
      male subjects, 2.8% of all subjects) exhibited a meaningful 36-s improvement in
      time-trial performance with sildenafil compared to placebo. CONCLUSIONS: In this
      group of endurance trained men and women, sildenafil had very little influence on
      cardiovascular hemodynamics, SaO2, and 6-km time-trial performance at a simulated
      altitude of ~3900 m. It appears that a very small percentage of endurance-trained
      men and women derive meaningful improvements in aerobic performance from
      sildenafil at a simulated altitude of ~3900 m.

PMID- 21962065
TI  - D-dimer is not elevated in asymptomatic high altitude climbers after descent to
      5340 m: the Mount Everest Deep Venous Thrombosis Study (Ev-DVT).
AB  - We performed this study to determine the prevalence of elevated D-dimer, a marker
      for deep venous thrombosis (DVT), in asymptomatic high altitude climbers. On-site
      personnel enrolled a convenience sample of climbers at Mt. Everest Base Camp
      (Nepal), elevation 5340 m (17,500 ft), during a single spring climbing season.
      Subjects were enrolled after descent to base camp from higher elevation. The
      subjects completed a questionnaire to evaluate their risk factors for DVT. We
      then performed a D-dimer test in asymptomatic individuals. If the D-dimer test
      was negative, DVT was considered ruled out. Ultrasound was available to perform
      lower-extremity compression ultrasounds to evaluate for DVT in case the D-dimer
      was positive. We enrolled 76 high altitude climbers. None had a positive D-dimer
      test. The absence of positive D-dimer tests suggests a low prevalence of DVT in
      asymptomatic high altitude climbers.

PMID- 21962066
TI  - High altitude sleep disturbances monitored by actigraphy and polysomnography.
AB  - AIMS: Data on sleep at altitude are scant due to the limited availability of
      polysomnography. Therefore, we investigated whether actigraphy might serve as a
      simple tool for monitoring sleep during altitude field studies. METHODS: Fourteen
      mountaineers participating in studies on dexamethasone prophylaxis of high
      altitude pulmonary edema were monitored by actigraphy and polysomnography during
      1 night at Zurich (490 m) and 4 nights at the Regina Margherita hut (4559 m).
      Total sleep time (TST) estimated by actigraphy was compared to polysomnography
      and subjective sleep quality. RESULTS: In 64 comparisons, mean differences+/-2SD
      (bias+/-limits of agreement) between actigraphy and polysomnography were 5+/-35
      min for TST and 1+/-7% for sleep efficiency. Correlations between subjective and
      polysomnographic estimates of sleep efficiency and sleep latency were
      nonsignificant. Medians of nocturnal oxygen saturation were 96% at 490 m and 74%
      81% during nights 1 to 4 at 4459 m (p<0.05 vs. 490 m). Medians of
      polysomnographic TST were similar at 490 m (451 min) and 4559 m (377-456 min
      during nights 1 to 4, p=NS) but the proportions of slow wave and REM sleep were
      reduced and arousals were more common (p<0.05 all instances). CONCLUSION:
      Actigraphy accurately estimates sleep efficiency and duration. Due to its
      portability and simple use and the potential application over several weeks, it
      is a convenient tool for investigating altitude effects on sleep during field
      studies.

PMID- 21962067
TI  - Poor sleep quality predicts decreased cognitive function independently of chronic
      mountain sickness score in young soldiers with polycythemia stationed in Tibet.
AB  - Little is known about the association between poor sleep and cognitive function
      in people with polycythemia at high altitude. The aim of this study was to survey
      the sleep quality of individuals with polycythemia at high altitude and determine
      its association with cognitive abilities. We surveyed 230 soldiers stationed in
      Tibet (all men; mean age 21-52+/-4.30 yr) at altitudes ranging from 3658 to 3996
      m. All participants were given a blood tests for hemoglobin level and a
      questionnaire survey of cognitive function. Polycythemia was defined as excessive
      erythrocytosis (Hb>=21 g/dL in men or >=19 g/dL in women). Poor sleepers were
      defined as having a global Pittsburgh Sleep Quality Index score (PSQI)>5.
      Cognitive abilities were determined by the Chinese revision of the Wechsler Adult
      Intelligence Scale and the Benton Visual Retention Test. Multiple linear
      regression analysis was used to determine the association between the PSQI and
      cognitive function. Logistic regression analysis was performed to determine the
      independent effect of sleep quality on cognitive function. The global PSQI score
      of enrolled participants was 8.14+/-3.79. Seventy-five (32.6%) soldiers were
      diagnosed with polycythemia. The proportion of poor sleepers was 1.45 times
      greater in those with polycythemia compared with those without polycythemia [95%
      (confidence interval) CI 1.82-2.56], and they had a statistically significant
      lower score for cognitive function. Multiple linear regression analysis showed
      that the global PSQI score was negatively associated with IQ (beta=0.11, 95% CI 
      0.16 to -0.05) and digit symbol scores (beta=0.66, 95% CI -0.86 to -0.44). Poor
      sleep quality was determined to be an independent predictor of impaired IQ [odds
      ratio (OR) 1.59, 95% CI 1.30-1.95] and digit symbol score (OR 1.18, 95% CI 1.07
      1.31) in logistic regression analysis. The present study showed that for young
      soldiers with polycythemia at high altitude impaired subjective sleep quality was
      an independent predictor of decreased cognitive function, especially IQ and
      verbal short-term memory.

PMID- 21962070
TI  - Intravenous iron supplementation may protect against acute mountain sickness: a
      randomized, double-blinded, placebo-controlled trial.
AB  - Acute mountain sickness (AMS) is a common and disabling condition that occurs in
      healthy individuals ascending to high altitude. Based on the ability of iron to
      influence cellular oxygen sensing pathways, we hypothesized that iron
      supplementation would protect against AMS. To examine this hypothesis, 24 healthy
      sea-level residents were randomized to receive either intravenous iron(III)
      hydroxide sucrose (200 mg) or saline placebo, before ascending rapidly to Cerro
      de Pasco, Peru (4340 m). The Lake Louise scoring system was used to assess
      incidence and severity of AMS at sea level and on the first full day at altitude.
      No significant difference in absolute AMS score was detected between the two
      groups either at baseline or at high altitude. However, the mean increase in AMS
      score was 65% smaller in the iron group than in the saline group (p<0.05), and
      the change in AMS score correlated negatively with the change in ferritin (R=
      0.43; p<0.05). Hematocrit and arterial oxygen saturation were unaffected by iron.
      In conclusion, this preliminary randomized, double-blinded, placebo-controlled
      trial suggests that intravenous iron supplementation may protect against the
      symptoms of AMS in healthy volunteers.

PMID- 21962068
TI  - Intermittent hypoxia mobilizes hematopoietic progenitors and augments cellular
      and humoral elements of innate immunity in adult men.
AB  - This study tested the hypothesis that intermittent hypoxia treatment (IHT)
      modulates circulating hematopoietic stem and progenitor cells (HSPC) and augments
      humoral and cellular components of innate immunity in young, healthy men. Ten
      subjects (group 1: age 31+/-4 yr) were studied before and at 1 and 7 days after a
      14-day IHT program consisting of four 5-min bouts/day of breathing 10% O2,
      lowering arterial O2 saturation to 84% to 85%, with intervening 5-min room-air
      exposures. Five more subjects (group 2: age 29+/-5 yr) were studied during 1 IHT
      session. Immunofluorescence detected HSPCs as CD45+CD34+ cells in peripheral
      blood. Phagocytic and bactericidal activities of neutrophils, circulating
      immunoglobulins (IgM, IgG, IgA), immune complexes, complement, and cytokines
      (erythropoietin, TNF-alpha, IL-4, IFN-gamma) were measured. In group 1, the HSPC
      count fell 27% below pre-IHT baseline 1 week after completing IHT, without
      altering erythrocyte and reticulocyte counts. The IHT program also activated
      complement, increased circulating platelets, augmented phagocytic and
      bactericidal activities of neutrophils, sharply lowered circulating TNF-alpha and
      IL-4 by >90% and ~75%, respectively, and increased IFN-gamma, particularly 1 week
      after IHT. During acute IHT (group 2), HSPC increased by 51% after the second
      hypoxia bout and by 19% after the fourth bout, and total leukocyte, neutrophil,
      monocyte, and lymphocyte counts also increased; but these effects subsided by 30
      min post-IHT. Collectively, these results demonstrate that IHT enhances innate
      immunity by mobilizing HSPC, activating neutrophils, and increasing circulating
      complement and immunoglobulins. These findings support the potential for eventual
      application of IHT for immunotherapy.

PMID- 21962069
TI  - Preservation of serotonin-mediated contractility in adult sheep pulmonary
      arteries following long-term high-altitude hypoxia.
AB  - Long-term hypoxia (LTH) can increase serotonin (5-HT) signaling as well as
      extracellular calcium entry in adult rodent pulmonary arteries (PA), and 5-HT is
      associated with pulmonary hypertension. Because LTH, 5-HT, and calcium entry are
      related, we tested the hypothesis that LTH increases 5-HT-mediated PA
      contractility and associated calcium influx through L-type Ca2+ channels,
      nonselective cation channels (NSCC), and reverse-mode sodium-Ca2+ exchange. We
      performed wire myography and confocal calcium imaging on pulmonary arteries from
      adult ewes that lived near sea level or were maintained at high-altitude (3801 m)
      for ~110 days. LTH did not increase the arterial medial wall thickness, nor did
      it affect the potency or efficacy for 5-HT-induced PA contraction. Ketanserin
      (100 nM), a 5-HT2A antagonist, shifted the 5-HT potency to a far greater extent
      than 1 MUM GR-55562, a 5-HT1B/D inhibitor. These influences were unaffected by
      LTH. The rank order for reducing 5-HT-induced PA contraction in normoxic animals
      was extracellular calcium removal~10 mM Ni2+~10 MUM verapamil~10 MUM nifedipine
      with 50 MUM SKF 96365>30 MUM KB-R7943~100 MUM flufenamic acid~10 MUM
      nifedipine~100 MUM Gd3+> 100 MUM La3+>500 MUM Ni2+~10 MUM diltiazem~50 MUM 2
      APB~100 MUM LOE 908. Contraction was not reduced by 100 MUM spermine or 30 MUM SN
      6. LTH increased the effects of KB-R7943 and mitigated those of nifedipine but
      did not affect calcium responses in imaging studies. Overall, in adult sheep,
      arterial structure and 5-HT2A and 5HT1B/D functions are preserved following LTH
      while the role of NSCC-related calcium-dependent contraction is increased. These
      elements indicate preservation of PA contractility in LTH with minimal functional
      changes.

PMID- 21962071
TI  - Freezing and frostbite on mount everest: new insights into wind chill and
      freezing times at extreme altitude.
AB  - Cold injury is an acknowledged risk factor for those who venture into high
      altitude regions. There is, however, little quantitative information on this risk
      that can be used to implement mitigation strategies. Here we provide the first
      characterization of the risk of cold injury near the summit of Mount Everest.
      This is accomplished through the application of a meteorological dataset that has
      been demonstrated to characterize conditions in the region as inputs to new
      parameterizations of wind chill equivalent temperature (WCT) and facial frostbite
      time (FFT). Throughout the year, the typical WCT near the summit of Everest is
      always <-30 degrees C, and the typical FFT is always less than 20 min. During the
      spring climbing season, WCTs of -50 degrees C and FFTs of 5 min are typical;
      during severe storms, they approach -60 degrees C and 1 min, respectively; values
      typically found during the winter. Further, we show that the summit barometric
      pressure is an excellent predictor of summit WCT and FFT. Our results provide the
      first quantitative characterization of the risk of cold injury on Mount Everest
      and also allow for the possibility of using barometric pressure, an easily
      observed parameter, in real time to characterize this risk and to implement
      mitigation strategies. The results also provide additional confirmation as to the
      extreme environment experienced by those attempting to summit Mount Everest and
      other high mountains.

PMID- 21962072
TI  - Mountain research and rescue on Denali: a short history from the 1980s to the
      present.
AB  - Alaska's Denali (Mt. McKinley), 6194 m, is the highest and perhaps most
      celebrated peak on the North American continent. The cold and stormy nature of
      this mountain just 3 degrees  of latitude south of the Arctic Circle enhances its
      legend as a challenging peak. It has been the desired objective of over 1000
      summit aspirants per climbing season for the last 20 years. As mountaineering
      traffic on the peak increased in the 1960s and 1970s, an increase in deaths and
      helicopter evacuations followed suit. These were largely owing to altitude
      illness, cold injuries, and trauma. By the late 1970s and early 1980s, the U.S.
      National Park Service (NPS) began exploring potential solutions regarding the
      problems with rescue scenarios in remote and hostile surroundings. The NPS
      eventually placed a team equipped with communications and medical supplies high
      on the mountain to remedy the problem. This seasonal high altitude camp,
      established in 1982, carried out clinical research, preventive education, and
      rescue work. Although this operation has undergone substantial changes since
      1982, it continues to serve Denali climbers each season and has likely reduced
      the frequency of serious accidents, death, and helicopter rescues. In addition, a
      parallel increase in NPS infrastructure, medical research, and mountain rescue on
      this peak has contributed to an increased benefit for climbers and others, which
      has served (and continues to serve) a wide range of interests, from the safety
      concerns of mountaineers to high altitude-related scientific discoveries
      advantageous to the scientific community.

PMID- 21962073
TI  - The 17th International Hypoxia Symposium: Hypoxia and Cancer, February 15-20,
      2011.

PMID- 21962074
TI  - UIAA/ICAR/ISMM Diploma of Mountain Medicine.

PMID- 21962076
TI  - Is there elliptic distortion in the light harvesting complex 2 of purple
      bacteria?
AB  - Single molecule spectroscopy (SMS) revealed an unusually large Gap between two
      major exciton peaks of the B850 unit of light harvesting complex 2 (LH2), which
      could be explained assuming elliptic distortion or k = 2 symmetry modulation in
      the site excitation energy. On the basis of extensive simulation of the SMS data
      and ensemble line shape, we found that uniform modulation of k = 2 symmetry
      cannot explain the dependence of intensity ratios on the Gap of the two major
      peaks, which are available from SMS, nor the ensemble line shape. Alternative
      models of disorder with k = 1 and k = 2 symmetry correlation are shown to
      reproduce these data reasonably well and can even explain the Gap distribution
      when it is assumed that the lower major peak in the SMS line shape is an
      intensity weighted average of k = 1- and k = 0 states.

PMID- 21962075
TI  - Use of folic acid and vitamin supplementation among adults with depression and
      anxiety: a cross-sectional, population-based survey.
AB  - BACKGROUND: Evidence suggests that folate deficiency may be causatively linked to
      depressive symptoms. However, little is known on the status of use of folic acid
      and vitamin supplements among people with mental disorders. This study examined
      the prevalence and the likelihood of use of folic acid or vitamin supplements
      among adults with depression and anxiety in comparison to those without these
      conditions. METHODS: Using data from 46, 119 participants (aged >= 18 years) in
      the 2006 Behavioral Risk Factor Surveillance System survey, we estimated the
      adjusted prevalence and odds ratios with 95% confidence intervals for taking
      folic acid and vitamin supplements among those with ever diagnosed depression (n
      = 8, 019), ever diagnosed anxiety (n = 5, 546) or elevated depressive symptoms (n
      = 3, 978, defined as having a depression severity score of >= 10 on the Patient
      Health Questionnaire-8 diagnostic algorithm). RESULTS: Overall, women were more
      likely than men to take folic acid supplements 1-4 times/day (50.2% versus 38.7%,
      P < 0.001) and vitamin supplements (62.5% versus 49.8%, P < 0.001). After
      multivariate adjustment, men with ever diagnosed depression or anxiety were 42%
      and 83%, respectively, more likely to take folic acid supplements < 1 time/day;
      44% and 39%, respectively, more likely to take folic acid supplements 1-4
      times/day; and 40% and 46%, respectively, more likely to take vitamin supplements
      compared to men without these conditions (P < 0.05 for all comparisons). Women
      with ever diagnosed depression were 13% more likely to take folic acid
      supplements 1-4 times/day and 15% more likely to take vitamin supplements than
      women without this condition (P < 0.05 for both comparisons). Use of folic acid
      and vitamin supplements did not differ significantly by elevated depressive
      symptoms in either sex. CONCLUSION: The prevalence and the likelihood of taking
      folic acid and vitamin supplements varied substantially by a history of diagnosed
      depression among both men and women and by a history of diagnosed anxiety among
      men, but not by presence of elevated depressive symptoms in either sex.

PMID- 21962077
TI  - Reviewing the use of ethylcellulose, methylcellulose and hypromellose in
      microencapsulation. Part 3: Applications for microcapsules.
AB  - This three-part review has been developed following the evaluation of literature
      where ethylcellulose, methylcellulose, or hypromellose was used to make
      microcapsules. Parts 1 and 2 of the review are published in separate papers. Part
      1 covers the various materials used to formulate microcapsules, and Part 2 covers
      the various techniques used to make microcapsules. In the current paper, Part 3
      covers the end-use applications for which microcapsules are used. Examples of
      applications to be covered include modified release, improved efficacy and
      safety, multiparticulate compression, improved processability and stability, and
      taste- and odor-masking. It is hoped that formulators can use Part 3 to
      understand the various end-use applications of microcapsules made from these
      encapsulating polymers. SciFinder was utilized to perform the literature search.
      SciFinder leverages literature databases, such as Chemical Abstracts Service
      Registry and Medline. A total of 379 references were identified during the
      review. The need for a three-part review reflects the extensive amount of
      literature identified concerning these three encapsulating polymers.

PMID- 21962079
TI  - Separating global and specific factors in developmental dyslexia.
AB  - The general goal of the study was to identify global and specific components in
      developmental dyslexia using various manipulations based on the rapid
      automatization paradigm (RAN). In two experiments, we used both factor analysis
      and the Rate-and-Amount Model to verify if one (or more) global factor(s) and a
      variety of specific effects contribute to the naming (and visual search) deficits
      in children with dyslexia.   Results of Experiment 1 indicated the presence of
      three global components: pictorial naming, detailed orthographic analysis, and
      visual search. Pictorial naming is predicated by typical RAN tasks (such as
      naming colors or objects), independent of set size, but also from a variety of
      other tasks including Stroop interference conditions. The detailed orthographic
      analysis factor accounts for naming of orthographic stimuli at high set size.
      Visual search marked tasks requiring the scanning of visual targets.   Results of
      Experiment 2 confirmed the separation between the pictorial naming and detailed
      orthographic analysis factors both in the original sample and in a new group of
      children. Furthermore, specific effects of frequency, lexicality, and length were
      shown to contribute to the reading deficit.   Overall, it is proposed that
      focusing on the profile of both global and specific effects provides a more
      effective and, at the same time, simpler account of the dyslexics' impairment.

PMID- 21962078
TI  - Breakpoint characterization of a novel large intragenic deletion of MUTYH
      detected in a MAP patient: case report.
AB  - BACKGROUND: MUTYH-associated polyposis (MAP) is a recessive, hereditary,
      colorectal cancer-predisposing syndrome caused by biallelic mutations in the
      MUTYH gene. Most MUTYH pathogenic variants are missense mutations, and until
      recently no gross genomic deletions had been described. CASE PRESENTATION: We
      have identified a large deletion in the MUTYH gene: a > 4.2 kb deletion
      encompassing exons 4-16. This is the second description of this rearrangement,
      which has been recently described as the first large deletion in this gene. The
      clinically suspected MAP patient was homozygous for this mutation and presented
      with no amplification products for 14 exons of MUTYH on initial screening.
      Deletion breakpoints were refined to base pair level through array comparative
      genomic hybridization (aCGH) analysis followed by sequencing. The identified
      breakpoints were located within intron 3 and 146 bp downstream of the 3' end of
      the gene, with the presence of an AluJr element adjacent to the distal
      breakpoint. The presence of a 2 bp insertion at the junction suggests the
      involvement of the non-homologous end joining (NHEJ) repair mechanism, possibly
      facilitated by rearrangement-promoting elements. Examination of the MUTYH locus
      revealed a high Alu density that may make this region prone to rearrangements.
      CONCLUSION: Large deletions are a possible mechanism for loss of function of the
      MUTYH gene, and investigation of such mutations may be important in identifying
      causative mutations in MAP patients.

PMID- 21962080
TI  - Human platelets express CAR with localization at the sites of intercellular
      interaction.
AB  - Adenovirus has a wide tissue tropism. The virus attaches to the surface of cells
      via the fiber protein knob binding to the Coxsackie and Adenovirus receptor known
      as CAR. Virus entry inside cells is facilitated by integrins alphaVbeta3 and
      alphaVbeta5. Mice platelets are shown to be the predominant Ad binding blood cell
      type and the virus is documented inside platelets. CAR was identified on human
      platelets in one study yet contradicted in another. The presence of CAR appears
      to be the most reasonable initial step for virus entry into platelets and is a
      key to the understanding of platelet adenovirus interaction. This study aimed to
      re investigate the presence of CAR on human platelets. Platelets were tested by
      indirect immune-fluorescence using rabbit H-300 polyclonal anti-CAR antibody and
      goat anti-rabbit IgG F(ab')2 Texas Red antibodies, alongside with CAR positive
      and negative controls. Platelets were found to express CAR on their surface and
      in contrast to the previous study only 3.5 +/- 1.9% of the tested platelets did
      express CAR. In addition, CAR was seen within intracellular aggregates localized
      at the sites of cell-cell contacts indicating that CAR expression might be
      upregulated in response to platelet stimulation. We confirm the presence of CAR
      on human platelets, we provide explanation to some of the discrepancies in this
      regards and we add that this receptor is localized at the sites of intercellular
      interaction.

PMID- 21962081
TI  - Diffusion tensor imaging-based fiber tracking for prediction of the position of
      the facial nerve in relation to large vestibular schwannomas.
AB  - OBJECT: The reliable preoperative visualization of facial nerve location in
      relation to vestibular schwannoma (VS) would allow surgeons to plan tumor removal
      accordingly and may increase the safety of surgery. In this prospective study,
      the authors attempted to validate the reliability of facial nerve diffusion
      tensor (DT) imaging-based fiber tracking in a series of patients with large VSs.
      Furthermore, the authors evaluated the potential of this visualization technique
      to predict the morphological shape of the facial nerve (tumor compression-related
      flattening of the nerve). METHODS: Diffusion tensor imaging and anatomical images
      (constructive interference in steady state) were acquired in a series of 22
      consecutive patients with large VSs and postprocessed with navigational software
      to obtain facial nerve fiber tracking. The location of the cerebellopontine angle
      (CPA) part of the nerve in relation to the tumor was recorded during surgery by
      the surgeon, who was blinded to the results of the fiber tracking. A correlative
      analysis was performed of the imaging-based location of the nerve compared with
      its in situ position in relation to the VS. RESULTS: Fibers corresponding to the
      anatomical location and course of the facial nerve from the brainstem to the
      internal auditory meatus were identified with the DT imaging-based fiber tracking
      technique in all 22 cases. The location of the CPA segment of the facial nerve in
      relation to the VS determined during surgery corresponded to the location of the
      fibers, predicted by the DT imaging-based fiber tracking, in 20 (90.9%) of the 22
      patients. No DT imaging-based fiber tracking correlates were found with the 2
      morphological types of the nerve (compact or flat). CONCLUSIONS: The current
      study of patients with large VSs has shown that the position of the facial nerve
      in relation to the tumor can be predicted reliably (in 91%) using DT imaging
      based fiber tracking. These are preliminary results that need further
      verification in a larger series.

PMID- 21962083
TI  - Single molecule and single atom sensors for atomic resolution imaging of
      chemically complex surfaces.
AB  - Individual Xe atoms as well as single CO and CH(4) molecules adsorbed at the tip
      apex of a scanning tunneling microscope (STM) function as microscopic force
      sensors that change the tunneling current in response to the forces acting from
      the surface. An STM equipped with any of these sensors is able to image the short
      range Pauli repulsion and thus resolve the inner structure of large organic
      adsorbate molecules. Differences in the performance of the three studied sensors
      suggest that the sensor functionality can be tailored by tuning the interaction
      between the sensor particle and the STM tip.

PMID- 21962082
TI  - The Cryptosporidium parvum kinome.
AB  - BACKGROUND: Hundreds of millions of people are infected with cryptosporidiosis
      annually, with immunocompromised individuals suffering debilitating symptoms and
      children in socioeconomically challenged regions at risk of repeated infections.
      There is currently no effective drug available. In order to facilitate the
      pursuit of anti-cryptosporidiosis targets and compounds, our study spans the
      classification of the Cryptosporidium parvum kinome and the structural and
      biochemical characterization of representatives from the CDPK family and a MAP
      kinase. RESULTS: The C. parvum kinome comprises over 70 members, some of which
      may be promising drug targets. These C. parvum protein kinases include members in
      the AGC, Atypical, CaMK, CK1, CMGC, and TKL groups; however, almost 35% could
      only be classified as OPK (other protein kinases). In addition, about 25% of the
      kinases identified did not have any known orthologues outside of Cryptosporidium
      spp. Comparison of specific kinases with their Plasmodium falciparum and
      Toxoplasma gondii orthologues revealed some distinct characteristics within the
      C. parvum kinome, including potential targets and opportunities for drug design.
      Structural and biochemical analysis of 4 representatives of the CaMK group and a
      MAP kinase confirms features that may be exploited in inhibitor design. Indeed,
      screening CpCDPK1 against a library of kinase inhibitors yielded a set of the
      pyrazolopyrimidine derivatives (PP1-derivatives) with IC50 values of < 10 nM. The
      binding of a PP1-derivative is further described by an inhibitor-bound crystal
      structure of CpCDPK1. In addition, structural analysis of CpCDPK4 identified an
      unprecedented Zn-finger within the CDPK kinase domain that may have implications
      for its regulation. CONCLUSIONS: Identification and comparison of the C. parvum
      protein kinases against other parasitic kinases shows how orthologue- and family
      based research can be used to facilitate characterization of promising drug
      targets and the search for new drugs.

PMID- 21962085
TI  - Tethered bilayer lipid membranes on mixed self-assembled monolayers of a novel
      anchoring thiol: impact of the anchoring thiol density on bilayer formation.
AB  - Tethered bilayer lipid membranes (tBLMs) are designed on mixed self-assembled
      monolayers (SAMs) of a novel synthetic anchoring thiol, 2,3-di-o
      palmitoylglycerol-1-tetraethylene glycol mercaptopropanoic acid ester (TEG-DP),
      and a new short dilution thiol molecule, tetraethylene glycol mercaptopropanoic
      acid ester (TEG). tBLM formation was accomplished by self-directed fusion of
      small unilamellar vesicles of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine.
      The influence of the dilution of the anchoring thiol molecule in the SAM on the
      vesicle fusion process and on the properties of the resulting tBLMs is studied.
      It is observed by quartz crystal microbalance that vesicle fusion is a one-step
      process for a pure TEG-DP SAM as well as for mixed SAMs containing a high
      concentration of the anchoring thiol. However, upon dilution of the anchoring
      thiol to moderate concentrations, this process is decelerated and possibly
      follows a pathway different from that observed on a pure TEG-DP SAM.
      Electrochemical impedance spectroscopy is used to qualitatively correlate the
      composition of the SAM to the electrical properties of the tBLM. In this paper we
      also delineate the necessity of a critical concentration of this anchoring TEG-DP
      thiol as a requisite for inducing the fusion of vesicles to form a tBLM.

PMID- 21962084
TI  - Nanoparticle-mediated measurement of target-drug binding in cancer cells.
AB  - Responses to molecularly targeted therapies can be highly variable and depend on
      mutations, fluctuations in target protein levels in individual cells, and drug
      delivery. The ability to rapidly quantitate drug response in cells harvested from
      patients in a point-of-care setting would have far reaching implications.
      Capitalizing on recent developments with miniaturized NMR technologies, we have
      developed a magnetic nanoparticle-based approach to directly measure both target
      expression and drug binding in scant human cells. The method involves covalent
      conjugation of the small-molecule drug to a magnetic nanoparticle that is then
      used as a read-out for target expression and drug-binding affinity. Using
      poly(ADP-ribose) polymerase (PARP) inhibition as a model system, we developed an
      approach to distinguish differential expression of PARP in scant cells with
      excellent correlation to gold standards, the ability to mimic drug
      pharmacodynamics ex vivo through competitive target-drug binding, and the
      potential to perform such measurements in clinical samples.

PMID- 21962086
TI  - Beverage patterns and trends among school-aged children in the US, 1989-2008.
AB  - BACKGROUND: High intake of sugar-sweetened beverages in childhood is linked to
      increased risk of obesity and type II diabetes later in life. Using three
      nationally representative surveys of dietary intake, we investigated beverage
      patterns and trends among US school-aged children from 1989/91 to 2007/08.
      METHODS: 3, 583 participants ages 6-11 y old were included. We reported per
      capita trends in beverage consumption, percent consuming, and amount per consumer
      for the following categories of beverages: sugar-sweetened beverages (SSB),
      caloric nutritional beverages (CNB) and low calorie beverages (LCB).
      Statistically significant differences were tested using the Student's t test in
      Stata 11. RESULTS: While per capita kcal contribution from total beverages
      remained constant over the study period, per capita consumption of SSBs increased
      and CNBs decreased in similar magnitude. The substantial increase in consumption
      of certain SSBs, such as fruit drinks and soda, high fat high sugar milk, and
      sports drinks, coupled with the decrease in consumption of high fat low sugar
      milk was responsible for this shift. The percent consuming SSBs as well as the
      amount per consumer increased significantly over time. Per capita intake of total
      milk declined, but the caloric contribution from high fat high sugar milk
      increased substantially. Among ethnicities, important differences in consumption
      trends of certain SSBs and 100% juice indicate the complexity in determining
      strategies for children's beverage calorie reduction. CONCLUSIONS: As upward
      trends of SSB consumption parallel increases in childhood obesity, educational
      and policy interventions should be considered.

PMID- 21962088
TI  - Allergen immunotherapy practice in the United States: guidelines, measures, and
      outcomes.
AB  - To discuss recent issues pertinent to allergen immunotherapy practice in the
      United States. Allergen extract preparation guidelines, updated allergen
      immunotherapy practice parameter (AIPP) guidelines, and evolving trends in how
      immunotherapy outcomes will be measured and assessed. Allergen extract
      preparation guidelines have been established by 2 entities: the US Pharmacopeia
      and an American Academy of Allergy, Asthma, and Immunology/American College of
      Allergy, Asthma, and Immunology/Joint Council of Allergy, Asthma, and Immunology
      Joint Task Force. Minor differences exist between these guidelines, but both
      focus on aseptic techniques and require that compounding personnel pass a written
      examination and annual media fill test. The AIPP third update provides new dosing
      recommendations for Bermuda grass, imported fire ant, and nonstandardized
      extracts distinguishing between pollen (0.5 mL of a 1:100 or 1:200 vol/vol) and
      mold/fungi or cockroach (highest tolerated dose) extracts. Because of limited and
      sometimes conflicting data on high and low proteolytic-containing extract
      compatibility, the AIPP continues to recommend against mixing these together.
      Although the AIPP does not specifically recommend a specific diluent, recent
      evidence suggests normal saline may not be as effective a stabilizer for extract
      dilutions as glycerin or human serum albumin. Currently, immunotherapy efficacy
      is determined with subjective assessments that rely on patient reporting, but
      this may change as health care reform evolves. It will likely become more
      important for US allergy/immunology practices to demonstrate immunotherapy
      comparative-effectiveness and report quality measures. Recent comparative
      effectiveness studies have demonstrated the cost-effectiveness of immunotherapy
      compared with symptomatic drug treatment.

PMID- 21962087
TI  - The human metabolic reconstruction Recon 1 directs hypotheses of novel human
      metabolic functions.
AB  - BACKGROUND: Metabolic network reconstructions formalize our knowledge of
      metabolism. Gaps in these networks pinpoint regions of metabolism where
      biological components and functions are "missing." At the same time, a major
      challenge in the post genomic era involves characterisation of missing biological
      components to complete genome annotation. RESULTS: We used the human metabolic
      network reconstruction RECON 1 and established constraint-based modelling tools
      to uncover novel functions associated with human metabolism. Flux variability
      analysis identified 175 gaps in RECON 1 in the form of blocked reactions. These
      gaps were unevenly distributed within metabolic pathways but primarily found in
      the cytosol and often caused by compounds whose metabolic fate, rather than
      production, is unknown. Using a published algorithm, we computed gap-filling
      solutions comprised of non-organism specific metabolic reactions capable of
      bridging the identified gaps. These candidate solutions were found to be
      dependent upon the reaction environment of the blocked reaction. Importantly, we
      showed that automatically generated solutions could produce biologically
      realistic hypotheses of novel human metabolic reactions such as of the fate of
      iduronic acid following glycan degradation and of N-acetylglutamate in amino acid
      metabolism. CONCLUSIONS: The results demonstrate how metabolic models can be
      utilised to direct hypotheses of novel metabolic functions in human metabolism; a
      process that we find is heavily reliant upon manual curation and biochemical
      insight. The effectiveness of a systems approach for novel biochemical pathway
      discovery in mammals is demonstrated and steps required to tailor future gap
      filling algorithms to mammalian metabolic networks are proposed.

PMID- 21962089
TI  - Can early household exposure influence the development of rhinitis symptoms in
      infancy? Findings from the PARIS birth cohort.
AB  - BACKGROUND: Allergic rhinitis (AR) has become the most prevalent chronic allergic
      disorder in childhood, and the role of environment has been questioned,
      particularly in early life. OBJECTIVE: To investigate the risk factors for
      rhinitis symptoms in infants included in the PARIS (Pollution and Asthma Risk: an
      Infant Study) birth cohort. METHODS: Infants were invited to participate at age
      18 months in a health examination conducted by a pediatrician. Allergic rhinitis
      was defined as the presence of rhinitis symptoms (runny nose, blocked nose,
      sneezing in the absence of a cold) combined with biological atopy (elevated total
      immunoglobulin E [IgE], specific IgE, or eosinophilia) and nonallergic rhinitis
      (NAR) as symptoms without biological atopy. Information about indoor exposures
      and lifestyle was collected during a telephone interview when the child was 1
      month of age. Risk factors for AR and NAR were studied by using a polytomous
      regression model. RESULTS: The prevalence of AR and NAR was 70/1,850 (3.8%) and
      99/1,850 (5.4%), respectively. Allergic rhinitis and NAR did not share similar
      risk factors. Male sex (odds ratio [OR] = 1.99 [1.19-3.32]), parental history of
      AR (OR = 1.89 [1.16-3.08]), low socioeconomic class (OR = 2.23 [1.05-4.72] for
      low vs high level), and the presence of cockroaches in the home (OR = 3.15 [1.67
      5.96]) were risk factors for AR. Conversely, the presence of particle-board
      furniture less than 12 months old in the child's bedroom was associated with an
      increased risk of NAR (OR = 1.87 [1.21-2.90]). CONCLUSIONS: This study should
      raise awareness about the impact of indoor exposures, particularly with regard to
      cockroaches and particle-board furniture, because they could influence the
      occurrence of noninfectious rhinitis.

PMID- 21962090
TI  - Evaluation of the Fight Asthma Now (FAN) program to improve asthma knowledge in
      urban youth and teenagers.
AB  - BACKGROUND: School-based asthma education programs targeting disadvantaged youth
      and teens with asthma are lacking. OBJECTIVES: To assess the impact of the Fight
      Asthma Now (FAN) educational program among 2 populations of predominantly low
      income minority students: youth (3(rd)-6(th) graders) and teens (7(th)-8(th)
      graders). METHODS: Chicago-area elementary schools were invited to participate in
      this stratified 2-arm study. Eligible schools were assigned to participate either
      in the intervention or in the control arm. Within each participating school,
      eligible students were recruited and grouped (stratified by grade and age) to
      form teen or youth classes. Participants completed a pre- and post-intervention
      asthma knowledge questionnaire and observation for spacer technique competency.
      The treatment group received the FAN curriculum between the evaluations. RESULTS:
      A sample of 26 low-income, predominantly minority-serving schools was recruited.
      Most participating schools were randomized in a 3:1 ratio to form 25 youth
      classes (19 intervention and 6 control group) and 16 teen classes (11
      intervention and 5 control group), resulting in 275 vs 69 youth and 141 vs 51
      teens in the intervention and control groups, respectively. Stratified analyses
      were performed, and clustering within the school and class was taken into
      consideration in analyses. Multilevel models adjusting for school, class,
      ethnicity, sex, and pretest score indicate that the FAN intervention
      significantly increased both knowledge and spacer competency test scores, among
      both the youth and teen participants (P = .011 with respect to knowledge score
      among teen students, P < .0001 for all other cases). CONCLUSIONS: This study
      suggests that FAN significantly increases asthma knowledge and spacer technique
      competency within this high-risk population.

PMID- 21962091
TI  - Comparison of bronchodilator response in patients with asthma and healthy
      subjects using spirometry and oscillometry.
AB  - BACKGROUND: Impulse oscillometry (IOS) is an effort-independent and patient
      friendly pulmonary function technique, but limited data are available that
      correlate the bronchodilator response using spirometry and IOS in adult asthmatic
      and healthy subjects. OBJECTIVE: To compare spirometry and IOS in ongoing
      bronchodilator response. METHODS: The study was a prospective evaluation of
      patients with asthma and healthy subjects attending screening at a research unit
      in a university teaching hospital. Reversibility testing was carried out using
      standardized American Thoracic Society/European Respiratory Society (ATS/ERS)
      criteria after administering 400 MUg salbutamol by AccuhalerTM. Impulse
      oscillometry measurements (resistance at 5 Hz [R5], resistance at 20 Hz [R20],
      reactance at 5 Hz [X5]) and spirometry (forced expiratory volume in 1 second
      [FEV(1)], forced vital capacity [FVC], forced expiratory flow from 25% to 75% of
      vital capacity [FEF(25-75)]) were recorded pre and postbronchodilator. RESULTS:
      Ninety-five asthmatic and 61 healthy subjects underwent screening. Mean percent
      (standard error of the mean [SEM]) baseline prebronchodilator FEV(1) was 83.99
      (2.23) for patients with asthma, and 99.25 (1.72) for healthy subjects. Baseline
      percent predicted IOS indices in the group with asthma were 162.22 (7.5) for R5;
      154.73 (4.71) for R20; and 441.72 (173.86) for X5. In healthy volunteers,
      corresponding values were 111.01 (3.96), 127.75 (4.12), and -229.80 (125.75). R5
      was the only IOS measure that showed correlation with spirometry (FEV(1)) in both
      groups. The mean percent (SEM) predicted postbronchodilator change in FEV(1) and
      R5 in patients with asthma was 6.35 (0.65) and -33.78 (4.43); correspondingly in
      healthy subjects it was 2.24 (0.32) and -14.91 (2.48). A negative correlation was
      demonstrated (r = -0.40, P < .001 between the 2 indices in patients with asthma.
      Linear regression modeling demonstrated that 1 unit change in %FEV(1) corresponds
      to a 2.5% change in %R5. CONCLUSIONS: Low-frequency IOS as R5 and spirometry as
      FEV(1) correlate in patients with asthma and healthy subjects, with changes that
      can be predicted by linear regression.

PMID- 21962092
TI  - Linear growth and bone maturation are unaffected by 1 year of therapy with
      inhaled flunisolide hydrofluoroalkane in prepubescent children with mild
      persistent asthma: a randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Inhaled corticosteroids (ICS) are the preferred long-term therapy for
      subjects with persistent asthma. However, concerns remain about potential effects
      of long-term ICS use on growth in children. OBJECTIVE: To determine the effect of
      1 year of inhalation therapy with flunisolide hydrofluoroalkane (HFA) on growth
      velocity and bone maturation in children with mild persistent asthma. METHODS: In
      this double-blind, placebo-controlled study, 218 prepubescent (Tanner Stage 1)
      children with mild persistent asthma ranging in age from 4 to 10 years were
      evaluated. After a 2-week run-in period, subjects were randomized (1:1) to 2
      puffs flunisolide HFA twice daily (85 MUg/puff) or placebo for 52 weeks. Height
      was assessed by stadiometry at each visit. Growth velocity (cm/52 weeks) was
      estimated by the slope of the linear regression of height over time. An
      independent assessor scored hand and wrist radiographs for bone development
      pretreatment and at week 52. Analysis of covariance was used for all efficacy
      endpoints. RESULTS: The 2 treatment groups were similar at baseline for sex,
      race, age, weight, and height. At the end of double-blind treatment, mean growth
      velocity was 6.01 +/- 1.84 cm/52 weeks for flunisolide HFA (n = 106) and 6.19 +/-
      1.30 cm/52 weeks for placebo (n = 112) (P = .425). Mean advancement in bone age
      during the 1-year study was similar for the 2 groups: 0.93 +/- 0.46 years for
      flunisolide HFA (n = 70) and 1.01 +/- 0.41 years for placebo (n = 75) (P = .128).
      CONCLUSIONS: In this study, flunisolide HFA did not suppress growth or bone
      maturation at the highest approved dose for children with persistent asthma.

PMID- 21962093
TI  - A cross-sectional study assessing the relationship between BMI, asthma, atopy,
      and eNO among schoolchildren.
AB  - BACKGROUND: Increased body weight may influence airway inflammatory mechanisms.
      OBJECTIVE: To assess whether overweight-obesity (OW-O), evaluated as increased
      body mass index, is associated either with exhaled nitric oxide (eNO), a marker
      of airway inflammation, or with allergic sensitization in a large sample of
      children and adolescents. METHODS: A cross-sectional, epidemiological study was
      performed on a population sample of schoolchildren evaluating 708 subjects (age
      10-16 years; BMI 13-39 kg/m(2)) by respiratory health questionnaire, skin prick
      tests, spirometry, and eNO measure. RESULTS: Prevalence rates were: OW-O 16.4%,
      asthma ever (A) 11.9%, and rhinoconjunctivitis (RC) 14.8%. Asthma ever and
      allergic sensitization were significantly more frequent among OW-O (21.0 and
      51.6%) than in non-OW-O (10.2 and 37.0%, respectively). The forced expiratory
      volume in 1 second (FEV(1))/forced vital capacity (FVC) ratio was not
      significantly different between OW-O and non-OW-O. Exhaled NO (median and
      interquartile range) was 15.3 (11.2-23.1) ppb in the overall sample, 20.3 (12.9
      35.8) ppb among allergic subjects, and 13.9 (10.6-18.3) ppb among nonallergic
      subjects (P<.0001). No significant difference between OW-O and non OW-O subjects
      was found in eNO levels. Similarly, OW-O subjects with A or RC did not show
      significantly higher eNO levels than non-OW-O. In a logistic regression model,
      presence of allergic sensitization, A, and RC, and not OW-O, were significant
      predictors of increased eNO. CONCLUSIONS: In children, OW-O was not associated
      with increased eNO levels, but it was an independent risk factor for asthma and
      allergic sensitization.

PMID- 21962094
TI  - Usefulness of specific IgE antibodies to omega-5 gliadin in the diagnosis and
      follow-up of Japanese children with wheat allergy.
AB  - BACKGROUND: Gliadins have been implicated in IgE-mediated allergy to ingested
      wheat. omega-5 gliadin seems to be a clinically relevant allergen component in
      children with immediate wheat allergy (WA), but contradictory results have been
      published. OBJECTIVES: To investigate whether specific IgE (sIgE) antibodies to
      recombinant omega-5 gliadin could be used as a marker for oral wheat challenge
      outcome in wheat-sensitized children and to study whether measurements of sIgE to
      omega-5 gliadin are useful in monitoring children with WA to assess whether the
      allergy is outgrown or persistent. METHODS: Eighty-eight serum samples from
      children sensitized to wheat were collected consecutively. sIgE to omega-5
      gliadin was related to a physician's diagnosis of WA. RESULTS: Sixty-seven of 88
      children sensitized to wheat were diagnosed as having WA. The geometric mean
      concentrations of sIgE to omega-5 gliadin were 2.04 kU(A)/L (range, <0.35-100
      kU(A)/L) in children with WA and 0.40 kU(A)/L (range, <0.35-1.8 kU(A)/L) in
      children without WA. At follow-up, after being on a wheat-free diet for
      approximately 2 years, the sIgE titers to omega-5 gliadin were below 0.35 kU(A)/L
      (mean, 0.34 kU(A)/L; range, 0.34-2.3 kU(A)/L) in 10 of 15 children with outgrown
      WA. Conversely, in 12 of 14 children with persistent WA, the sIgE titers to omega
      5 gliadin were still elevated (mean, 5.89 kU(A)/L; range, 0.34-16.3 kU(A)/L).
      CONCLUSIONS: sIgE to omega-5 gliadin can be used as an accurate alternative to
      potentially dangerous wheat food challenges in monitoring WA.

PMID- 21962095
TI  - Histamine and allergen skin reactivity in the elderly population: results from
      the Korean Longitudinal Study on Health and Aging.
AB  - BACKGROUND: The allergen skin prick test is the most representative diagnostic
      test for atopy, but its use has been limited because of the belief that skin
      reactivity decreases with aging. OBJECTIVE: To investigate skin reactivity and
      influencing factors in the elderly population. METHODS: This cross-sectional
      analysis included 854 subjects (aged >=65 years) who participated in the Korean
      Longitudinal Study on Health and Aging cohort (September 2005 to August 2006) and
      underwent allergen skin prick tests. Skin prick tests were performed with 1 mg/mL
      of histamine and a panel of 12 aeroallergens that are common in Korea. The wheal
      diameters were measured and compared to identify the factors associated with skin
      reactivity. RESULTS: Older age and female sex were associated with reduced
      histamine skin reactivity in elderly subjects. This age-related decrease was
      apparent only among women, the reasons for which were not identified. In contrast
      to histamine, wheal response size induced by 2 major allergens, Dermatophagoides
      pteronyssinus and Dermatophagoides farinae, did not show sex differences and did
      not decrease with age among the subjects showing allergen-induced wheal size
      greater than 0 mm. CONCLUSIONS: This analysis demonstrates that age and sex can
      independently influence histamine skin reactivity among the elderly population.
      The allergen-induced wheal sizes did not decrease with age. The discrepancy
      between histamine and allergen skin reactivity may warrant further evaluation to
      redefine the cutoff value for the determination of a positive skin test result in
      elderly subjects.

PMID- 21962096
TI  - Variations in expression of matrix metalloproteinase-9 and tissue inhibitor of
      metalloproteinase-1 in nasal mucosa of aspirin-sensitive versus aspirin-tolerant
      patients with nasal polyposis.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) are key enzymes responsible for
      extracellular matrix degradation contributing to the progressive histological
      changes seen in lower airway disease, including asthma. MMP-9 and TIMP-1 have
      also shown some role in the pathogenesis of chronic rhinosinusitis (CRS) and
      nasal polyposis (NP). OBJECTIVE: We aim to determine variability in expression of
      MMP-9 and its inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), in
      sinus tissue from distinct patient populations presenting with nasal polyposis.
      METHODS: The expression of MMP-9 and TIMP-1 was investigated in nasal polyp
      tissue from 6 aspirin-sensitive (AS) and 6 aspirin-tolerant (AT) patients
      undergoing endoscopic sinus surgery for chronic rhinosinusitis with nasal
      polyposis (CRSwNP). Sinus mucosa from 6 patients with chronic rhinosinusitis
      without nasal polyposis (CRSsNP) was used as control. The MMP-9 and TIMP-1
      expression was measured using immunofluorescence technique and graded using
      manual and computerized methods. RESULTS: Expression of TIMP-1 was significantly
      reduced in the AS group when compared with both the AT and CRSsNP (control)
      groups (P < .001). The MMP-9/TIMP-1 ratio was significantly increased in the AS
      group when compared with other patient groups (P < .001). The MMP- 9 expression
      was similar between study and control groups. CONCLUSION: These results support
      the importance of MMP-9 and TIMP-1 expression in nasal polyp formation. The
      decreased expression of TIMP-1 in AS patients may promote the effects of MMP-9
      expression and thus contribute to tissue remodeling and inflammatory changes.
      This finding may lead to further understanding of disease severity and resistance
      to treatment in this group of patients, as well as the pathogenesis of nasal
      polyps.

PMID- 21962097
TI  - Neuropeptide levels in nasal secretions from patients with and without chronic
      cough.
AB  - BACKGROUND: The pathophysiology of upper airway cough syndrome is not well
      understood. OBJECTIVE: To investigate the levels of neuropeptides found in nasal
      mucus of subjects with and without the complaint of chronic cough. METHODS:
      Preformed nasal mucus from 26 subjects complaining of postnasal drip with chronic
      cough and 17 without self-reported chronic cough was collected at the time of
      presentation. The nasal secretions were assayed for 3 neuropeptides-substance P
      (SP), calcitonin gene-related peptide (CGRP), and Neurokinin A (NKA)-that have
      been previously linked to chronic cough. RESULTS: Coughing subjects with
      postnasal drip have significantly higher levels of CGRP and SP than noncoughing
      subjects with postnasal drip (69.0 ng vs 4.6 ng, P < .001 and 4.5 ng vs 3.4 ng, P
      = .004). The differences in NKA levels in nasal secretions between coughing and
      noncoughing subjects did not reach statistical significance (16.3 ng vs 3.4 ng, P
      = .067). CONCLUSIONS: Both CGRP and SP levels are elevated in preformed nasal
      secretions of coughing subjects when compared with noncoughing subjects.
      Additional studies are needed to clarify whether CGRP and SP levels in preformed
      nasal secretions may assist in diagnosis or predicting treatment response in
      patients presenting with chronic cough.

PMID- 21962098
TI  - Nasal carbon dioxide for the symptomatic treatment of perennial allergic
      rhinitis.
AB  - BACKGROUND: Brief nasal carbon dioxide insufflation has previously been shown to
      provide rapid relief of the symptoms of allergic rhinitis. OBJECTIVE: To examine
      the safety and efficacy of nasal carbon dioxide on the symptoms of perennial
      allergic rhinitis. METHODS: This was a randomized, double-blind, placebo
      controlled, multicenter, in-clinic study that evaluated 2 flow rates (5 or 10
      mL/s) and 2 administration durations (10 or 30 seconds per nostril) for nasal
      carbon dioxide vs placebo. Study participants rated their symptoms in clinic for
      4 hours after administration and then through 24 hours outside the clinic. A
      total of 348 symptomatic patients with a minimum 2-year history of perennial
      allergic rhinitis requiring pharmacotherapy were randomized and treated. RESULTS:
      The mean change in total nasal symptom score from baseline at 30 minutes (the
      primary end point) showed greater improvement in the nasal carbon dioxide-treated
      groups compared with placebo. This change was statistically significant in the
      group treated with 10 mL/s for 10 seconds per nostril: -4.69 carbon dioxide vs 
      2.00 placebo (P = .03). The effect of a single dose lasted approximately 4 to 6
      hours. The mean change from baseline at 30 minutes in total nonnasal symptom
      score was also statistically significant (-4.06 carbon dioxide vs -2.25 placebo,
      P = .029) for this group. The most common adverse events were nasal discomfort,
      lacrimation, and headache. CONCLUSION: The study provides further evidence that
      nasal carbon dioxide is a potentially efficacious treatment for the symptoms of
      allergic rhinitis.

PMID- 21962099
TI  - Characterization of the methacholine PC15.

PMID- 21962100
TI  - Agreement between parent and student responses to an asthma and allergy
      questionnaire in a diverse, inner-city elementary school population.

PMID- 21962101
TI  - Adverse reactions to the allergen conjunctival provocation test.

PMID- 21962102
TI  - Severe steroid-dependent idiopathic angioedema with response to rituximab.

PMID- 21962103
TI  - Angioedema associated with dutasteride therapy.

PMID- 21962104
TI  - Fixed drug eruption caused by mesna.

PMID- 21962105
TI  - MOC: data, no hype.

PMID- 21962106
TI  - On the cover - brown rat.

PMID- 21962107
TI  - Clinical and subclinical pancreatitis in a cohort of patients diagnosed with
      systemic lupus erythematosus.
AB  - OBJECTIVES: To evaluate amylase and lipase levels in a cohort of patients
      diagnosed with SLE, identify patients with subclinical and clinical pancreatitis
      and investigate factors associated. METHODS: Demographic, clinical and laboratory
      data were collected, including recent clinical symptoms possibly related to
      pancreatitis, use of medication, disease activity (SLEDAI-2K), and serum amylase
      and lipase levels. Patients with pancreatic enzyme levels >= 1.5 times in excess
      of the upper limit of normal and/or patients with clinical suspicion of
      pancreatitis were submitted to abdominal CT or US. RESULTS: The study included
      136 SLE patients aged 33.9 +/- 11.2 years. Three patients (2.2%) were diagnosed
      with clinical pancreatitis and 7 (5.1%) with subclinical pancreatitis. Multiple
      causal factors were associated with increased enzymes levels such as activity of
      the disease, drug toxicity, hypertriglyceridemia and chronic kidney failure.
      Patients with clinical and subclinical pancreatitis (n=10) when compared with
      pancreatitis-free patients had more SLE active, levels were lower for
      haemoglobin, platelets and albumin, and higher for triglycerides and AST.
      Thrombocytopenia, high blood sedimentation rate and hypertriglyceridemia were the
      only variables associated with pancreatitis in the logistic regression model.
      CONCLUSIONS: The prevalence of clinical and subclinical pancreatitis in SLE
      patients was low and associated with multiple potential factors. The association
      of thrombocytopenia and pancreatitis in SLE patients requires further studies.

PMID- 21962108
TI  - Lactam-stabilized helical analogues of the analgesic MU-conotoxin KIIIA.
AB  - MU-Conotoxin KIIIA (MU-KIIIA) blocks mammalian voltage-gated sodium channels
      (VGSCs) and is a potent analgesic following systemic administration in mice.
      Previous structure-activity studies of MU-KIIIA identified a helical
      pharmacophore for VGSC blockade. This suggested a route for designing truncated
      analogues of MU-KIIIA by incorporating the key residues into an alpha-helical
      scaffold. As (i, i+4) lactam bridges constitute a proven approach for stabilizing
      alpha-helices, we designed and synthesized six truncated analogues of MU-KIIIA
      containing single lactam bridges at various locations. The helicity of these
      lactam analogues was analyzed by NMR spectroscopy, and their activities were
      tested against mammalian VGSC subtypes Na(V)1.1 through 1.7. Two of the
      analogues, Ac-cyclo9/13[Asp9,Lys13]KIIIA7-14 and Ac-cyclo9/13[Lys9,Asp13]KIIIA7
      14, displayed MUM activity against VGSC subtypes Na(V)1.2 and Na(V)1.6;
      importantly, the subtype selectivity profile for these peptides matched that of
      MU-KIIIA. Our study highlights structure-activity relationships within these
      helical mimetics and provides a basis for the design of additional truncated
      peptides as potential analgesics.

PMID- 21962112
TI  - The presence of social support messages on YouTube videos about inflammatory
      bowel disease and ostomies.
AB  - The purpose of this study was to explore the types of social support messages
      YouTube users posted on medical videos. Specifically, the study compared messages
      posted on inflammatory bowel disease-related videos and ostomy-related videos.
      Additionally, the study analyzed the differences in social support messages
      posted on lay-created videos and professionally-created videos. Conducting a
      content analysis, the researchers unitized the comments on each video; the total
      number of thought units amounted to 5,960. Researchers coded each thought unit
      through the use of a coding scheme modified from a previous study. YouTube users
      posted informational support messages most frequently (65.1%), followed by
      emotional support messages (18.3%), and finally, instrumental support messages
      (8.2%).

PMID- 21962113
TI  - Substrate inhibition kinetics in drug metabolism reactions.
AB  - Inhibition of enzyme activity at high substrate concentrations, so-called
      "substrate inhibition," is commonly observed and has been recognized in drug
      metabolism reactions since the last decade. Although the importance of such
      "atypical" kinetics in vivo remains poorly understood, a substrate with substrate
      inhibition kinetics has been shown to unconventionally alter the metabolism of
      other substrates. In recent years, it is becoming increasingly evident that the
      mechanisms for substrate inhibition are highly complex, which are possibly
      contributed by multiple (at least two) binding sites within the enzyme protein,
      the formation of a ternary dead-end enzyme complex, and/or the ligand-induced
      changes in enzyme conformation. This review primarily discusses the mechanisms
      for substrate inhibition displayed by the important drug-metabolizing enzymes,
      such as cytochrome p450s, UDP-glucuronyltransferases, and sulfotransferases.
      Kinetic modeling of substrate inhibition in the absence or presence of a modifier
      is another central issue in this review because of its importance in the
      determination of kinetic parameters and in vitro/in vivo predictions.

PMID- 21962114
TI  - Electronic structure and stability of fullerene C82 isolated-pentagon-rule
      isomers.
AB  - All nine isolated-pentagon-rule isomers of fullerene C(82) were investigated by
      the DFT method with the B3LYP functional at the 6-31G, 6-31G*, and 6-31+G*
      levels. The distribution of single, double, and delocalized pi-bonds in the
      molecules of these isomers is shown for the first time. The obtained results are
      fully supported by DFT quantum-chemical calculations of electronic and
      geometrical structures of these isomers. The molecules of isomers 7 (C(3v)), 8
      (C(3v)), and 9 (C(2v)) contain some radical substructures (such as the phenalenyl
      radical substructure), which indicates that they are unstable and cannot be
      obtained as empty molecules. Thus, there is a possibility of obtaining them only
      as endohedral metallofullerenes or exohedral derivatives. Isomers 1 (C(2)), 2
      (C(s)), 4 (C(s)), 5 (C(2)), and 6 (C(s)) with closed electronic shell are
      supposed to be stable, resembling isomer 3 (C(2)), which has just been extracted
      experimentally as an empty fullerene. We assume they can be produced as empty
      molecules.

PMID- 21962116
TI  - Kinetics of polymerization of a liquid with nanosize structural heterogeneities.
AB  - We report the effects of chemically reacting, nanometer-size structural
      heterogeneity on a polymerization process. Heterogeneity is introduced by adding
      2 nm size molecules of polyhedral oligomeric silsesquioxane with multiepoxide
      groups (POSS) while maintaining stoichiometry of a polymerizing triamine
      diepoxide mixture. Calorimetric studies show that POSS addition first increases
      the polymerization rate and then decreases it progressively more. In the presence
      of nanometer-scale structural heterogeneity, diffusion-controlled kinetics begins
      sooner in time. The enthalpy of polymerization decreases with the amount of POSS
      heterogeneity according to the mixture rule; the glass-liquid transition
      endotherm of the partially polymerized state becomes broader, and the enthalpy of
      post polymerization decreases. The POSS-alone mixture polymerizes relatively
      slower, and the glass-liquid transition exotherm of the polymerized state is
      indistinguishably broad. Both are attributed to the distribution of diffusion
      rates or dispersive kinetics, and the development of dynamic heterogeneity more
      rapidly for the POSS-only mixture than for others. Increase in the polymerization
      rate on initial addition of nanometer-size POSS and then decrease on further
      addition is explained in terms of decoupling of diffusion from viscous flow, that
      is, when the diffusion rate decreases less rapidly with the polymerization time
      than the viscosity increases.

PMID- 21962115
TI  - An integrated structural intervention to reduce vulnerability to HIV and sexually
      transmitted infections among female sex workers in Karnataka state, south India.
AB  - BACKGROUND: Structural factors are known to affect individual risk and
      vulnerability to HIV. In the context of an HIV prevention programme for over
      60,000 female sex workers (FSWs) in south India, we developed structural
      interventions involving policy makers, secondary stakeholders (police, government
      officials, lawyers, media) and primary stakeholders (FSWs themselves). The
      purpose of the interventions was to address context-specific factors (social
      inequity, violence and harassment, and stigma and discrimination) contributing to
      HIV vulnerability. We advocated with government authorities for HIV/AIDS as an
      economic, social and developmental issue, and solicited political leadership to
      embed HIV/AIDS issues throughout governmental programmes. We mobilised FSWs and
      appraised them of their legal rights, and worked with FSWs and people with
      HIV/AIDS to implement sensitization and awareness training for more than 175
      government officials, 13,500 police and 950 journalists. METHODS: Standardised,
      routine programme monitoring indicators on service provision, service uptake, and
      community activities were collected monthly from 18 districts in Karnataka
      between 2007 and 2009. Daily tracking of news articles concerning HIV/AIDS and
      FSWs was undertaken manually in selected districts between 2005 and 2008.
      RESULTS: The HIV prevention programme is now operating at scale, with over 60,000
      FSWs regularly contacted by peer educators, and over 17,000 FSWs accessing
      project services for sexually transmitted infections monthly. FSW membership in
      community-based organisations has increased from 8,000 to 37,000, and over 46,000
      FSWs have now been referred for government-sponsored social entitlements. FSWs
      were supported to redress > 90% of the 4,600 reported incidents of violence and
      harassment reported between 2007-2009, and monitoring of news stories has shown a
      50% increase in the number of positive media reports on HIV/AIDS and FSWs.
      CONCLUSIONS: Stigma, discrimination, violence, harassment and social equity
      issues are critical concerns of FSWs. This report demonstrates that it is
      possible to address these broader structural factors as part of large-scale HIV
      prevention programming. Although assessing the impact of the various components
      of a structural intervention on reducing HIV vulnerability is difficult,
      addressing the broader structural factors contributing to FSW vulnerability is
      critical to enable these vulnerable women to become sufficiently empowered to
      adopt the safer sexual behaviours which are required to respond effectively to
      the HIV epidemic.

PMID- 21962124
TI  - 1H Indirect detected 13C Low-Abundance Single-transition correlation Spectroscopy
      (HICLASS)-13C homonuclear correlation at natural abundance.
AB  - A novel proton-detected (13)C homonuclear correlation experiment is reported at
      natural abundance, viz., (1)H Indirect detected (13)C Low-Abundance Single
      transition correlation Spectroscopy (HICLASS). HICLASS is based on the evolution
      of (13)C single-quantum single transitions, followed by their mixing, and (1)H
      detection subsequent to heteronuclear transfer. Reduced relaxation losses during
      the evolution time and partial selectivity in the (1)H multiplet structure result
      in enhanced sensitivity of HICLASS. The superior performance of HICLASS is
      demonstrated for (1)H-detected (13)C correlation work.

PMID- 21962117
TI  - Association of genetic variants in the promoter region of genes encoding p22phox
      (CYBA) and glutamate cysteine ligase catalytic subunit (GCLC) and renal disease
      in patients with type 1 diabetes mellitus.
AB  - BACKGROUND: Oxidative stress is recognized as a major pathogenic factor of
      cellular damage caused by hyperglycemia. NOX/NADPH oxidases generate reactive
      oxygen species and NOX1, NOX2 and NOX4 isoforms are expressed in kidney and
      require association with subunit p22phox (encoded by the CYBA gene). Increased
      expression of p22phox was described in animal models of diabetic nephropathy. In
      the opposite direction, glutathione is one of the main endogenous antioxidants
      whose plasmatic concentrations were reported to be reduced in diabetes patients.
      The aim of the present investigation was to test whether functional single
      nucleotide polymorphisms (SNPs) in genes involved in the generation of NADPH
      dependent O2*- (-675 T -> A in CYBA, unregistered) and in glutathione metabolism
      (-129 C -> T in GCLC [rs17883901] and -65 T -> C in GPX3 [rs8177412]) confer
      susceptibility to renal disease in type 1 diabetes patients. METHODS: 401
      patients were sorted into two groups according to the presence (n = 104) or
      absence (n = 196) of overt diabetic nephropathy or according to glomerular
      filtration rate (GFR) estimated by Modification of Diet in Renal Disease (MDRD)
      equation: >= 60 mL (n = 265) or < 60 mL/min/1.73 m2 (n = 136) and were genotyped.
      RESULTS: No differences were found in the frequency of genotypes between diabetic
      and non-diabetic subjects. The frequency of GFR < 60 mL/min was significantly
      lower in the group of patients carrying CYBA genotypes T/A+A/A (18.7%) than in
      the group carrying the T/T genotype (35.3%) (P = 0.0143) and the frequency of GFR
      < 60 mL/min was significantly higher in the group of patients carrying GCLC
      genotypes C/T+T/T (47.1%) than in the group carrying the C/C genotype (31.1%) (p
      = 0.0082). Logistic regression analysis identified the presence of at least one A
      allele of the CYBA SNP as an independent protection factor against decreased GFR
      (OR = 0.38, CI95% 0.14-0.88, p = 0.0354) and the presence of at least one T
      allele of the GCLC rs17883901 SNP as an independent risk factor for decreased GFR
      (OR = 2.40, CI95% 1.27-4.56, p = 0.0068). CONCLUSIONS: The functional SNPs CYBA 
      675 T -> A and GCLC rs17883901, probably associated with cellular redox
      imbalances, modulate the risk for renal disease in the studied population of type
      1 diabetes patients and require validation in additional cohorts.

PMID- 21962125
TI  - Comparative use of turkey and chicken wing brachial artery models for
      microvascular anastomosis training.
AB  - OBJECT: The aim of this study was to describe a turkey wing model for
      microvascular anastomosis training and compare it to the previously outlined
      chicken wing model. METHODS: The authors compared diameter measurements in each
      of 5 turkey and 5 chicken brachial arteries at 3 equidistant points. Usable
      vessel length was measured (from joint to joint) in each of the specimens. A
      survey was created and distributed at a bypass training course to assess the
      attendees' impressions of various practice models used for bypass. RESULTS: The
      turkey wing brachial artery was consistently larger in diameter (p < 0.01) and
      longer (p < 0.01) than the chicken wing artery and showed less variability in the
      vessel diameter (1.47 +/- 0.14 mm in the turkey vs 1.07 +/- 0.25 mm in the
      chicken). In a survey of 15 bypass course participants, the live rat training
      model scored highest overall and was ranked as the best model for training;
      however, the turkey wing model was ranked second best and was consistently scored
      ahead of the chicken wing and silastic tube training models. CONCLUSIONS: The
      authors' institutional preference has shifted to the use of a turkey wing artery
      as the initial model for microanastomosis training. Advantages in terms of vessel
      size and tissue durability favor this model over the chicken wing as part of a
      graduated instruction process.

PMID- 21962126
TI  - Single-nucleotide resolution analysis of the transcriptome structure of
      Clostridium beijerinckii NCIMB 8052 using RNA-Seq.
AB  - BACKGROUND: Clostridium beijerinckii is an important solvent producing
      microorganism. The genome of C. beijerinckii NCIMB 8052 has recently been
      sequenced. Although transcriptome structure is important in order to reveal the
      functional and regulatory architecture of the genome, the physical structure of
      transcriptome for this strain, such as the operon linkages and transcript
      boundaries are not well understood. RESULTS: In this study, we conducted a single
      nucleotide resolution analysis of the C. beijerinckii NCIMB 8052 transcriptome
      using high-throughput RNA-Seq technology. We identified the transcription start
      sites and operon structure throughout the genome. We confirmed the structure of
      important gene operons involved in metabolic pathways for acid and solvent
      production in C. beijerinckii 8052, including pta-ack, ptb-buk, hbd-etfA-etfB-crt
      (bcs) and ald-ctfA-ctfB-adc (sol) operons; we also defined important operons
      related to chemotaxis/motility, transcriptional regulation, stress response and
      fatty acids biosynthesis along with others. We discovered 20 previously non
      annotated regions with significant transcriptional activities and 15 genes whose
      translation start codons were likely mis-annotated. As a consequence, the
      accuracy of existing genome annotation was significantly enhanced. Furthermore,
      we identified 78 putative silent genes and 177 putative housekeeping genes based
      on normalized transcription measurement with the sequence data. We also observed
      that more than 30% of pseudogenes had significant transcriptional activities
      during the fermentation process. Strong correlations exist between the expression
      values derived from RNA-Seq analysis and microarray data or qRT-PCR results.
      CONCLUSIONS: Transcriptome structural profiling in this research provided
      important supplemental information on the accuracy of genome annotation, and
      revealed additional gene functions and regulation in C. beijerinckii.

PMID- 21962127
TI  - Ligand-induced structural evolution of Pt55 nanoparticles: amine versus thiol.
AB  - We report the geometric and electronic effects of amine (with one lone pair
      electron) and thiol (with two lone pair electrons) ligands on the structural
      transformation of Pt(55) nanoparticles (NPs) by first-principles calculation.
      Although a cuboctahedral (COh) structure is less stable than an icosahedral (Ih)
      structure by 1.36 eV for a bare Pt(55) NP, the activation barrier from the COh to
      the Ih structure is very high, by 1.97 eV, indicating that it would be difficult
      to observe the structural evolution of a COh structure to an Ih structure for a
      bare Pt(55) NP at ambient temperature. However, with the help of the adsorption
      of methylamine, the structural evolution from a COh structure to an Ih structure
      is accomplished by the Mackay transformation. This transformation is driven by a
      combination of both the external forces resulting from the adsorption of the
      ligand, which pull out the Pt atoms on the face sites of NPs in a radial
      direction, and the contraction forces in a tangential direction. As more
      methylamine is added, the Ih structure is observed to return to the original COh
      structure owing to the directional orbital hybridization that occurs between the
      Pt NPs and the methylamine. In contrast, such structural evolutions are not
      observed in the case of methylthiol because the sulfur (S) in the ligand has two
      lone pair electrons, leading to two Pt-S bonds. As a result, the radial-directed
      external force that the NPs experience because of the adsorption of methylthiols
      is much lower than that found in methylamine-ligated NPs. Furthermore, the
      adsorption of methylthiol leads to an expansion (not contraction) in the
      tangential direction, which does not qualify as a Mackay transformation. Thus,
      the Pt NPs ligated with methylthiol do not have a driving force strong enough to
      cause structural change. The methylthiol-stabilized Pt NPs retain their initial
      COh structure despite an abundance of ligand adsorption. From these results, we
      suggest that the NP structure can be controlled by varying the amount and species
      of ligands.

PMID- 21962128
TI  - A qualitative investigation of Hispanic construction worker perspectives on
      factors impacting worksite safety and risk.
AB  - BACKGROUND: Hispanic workers have higher rates of injury and death on
      construction worksites than workers of other ethnicities. Language barriers and
      cultural differences have been hypothesized as reasons behind the disparate
      rates. METHODS: We conducted two series of focus groups with union and non-union
      Hispanic construction workers to ask them about their perceptions of the causes
      for the unequal rates. Spanish transcripts were translated and coded in QSR NVivo
      software for common themes. RESULTS: Workers reported a difficult work
      environment characterized by supervisor pressure, competition for jobs and
      intimidation with regard to raising safety concerns. Language barriers or
      cultural factors were not strongly represented as causative factors behind the
      rates. CONCLUSION: The results of this study have informed the development of an
      intervention trial that seeks to prevent falls and silica dust exposure by
      training contractors employing Hispanic construction workers in the elements of
      safety leadership, including building respect for their Hispanic workers and
      facilitating their participation in a safety program.

PMID- 21962129
TI  - Discovery and resolve: the Human Genetics Society of Australasia Oration 2011.
AB  - Human genetics spans every facet of biology from molecular science, through
      laboratory and clinical practice, to psychology and anthropology. In each of
      these areas, the history of human genetics has been punctuated by paradigm shifts
      in knowledge. Each such new concept has been received with skepticism, often with
      perplexity, and sometimes with frank incredulity. Such comprise the datum
      milestones along the path leading to our present corpus of genetic knowledge. In
      parallel to the personal threats to Copernicus and Galileo in the field of
      astronomy in the 17th century, almost all genetic discoveries of the 19th and
      20th centuries were seen as challenges to the received wisdom, and sometimes the
      social order, of their time and place. Researchers, scientists and clinicians
      encountering such new and often-heretical paradigm shifts have required
      considerable resolve to promote and publish their work. Just as in the field of
      astronomy, new directions in genetics have threatened not only the reputations
      and sometimes the careers of scientists, but also have been challenges to
      fundamental religious and sociological beliefs in society more broadly. Examples
      followed the discovery of biological sexual dimorphism (in plants as well as
      animals) by Nehemiah Grew (1641-1712). Darwinian evolution, Mendel's First and
      Second Laws, the existence of mitochondrial genes, apoptosis and its genetic
      basis, and uniparental disomy are more recent examples. Many of these new
      revelations, which today have led to the current understanding of fundamental
      biology, were discovered by individuals working in relative isolation. To promote
      and publish findings that fundamentally challenge received wisdom continues to
      require considerable resolve, if not courage. Herein lies a message for all
      clinicians and researchers.

PMID- 21962130
TI  - Crying without a cause and being easily upset in two-year-olds: heritability and
      predictive power of behavioral problems.
AB  - In order to estimate the influence of genetic and environmental factors on
      'crying without a cause' and 'being easily upset' in 2-year-old children, a large
      twin study was carried out. Prospective data were available for ~18,000 2-year
      old twin pairs from the Netherlands Twin Register. A bivariate genetic analysis
      was performed using structural equation modeling in the Mx software package. The
      influence of maternal personality characteristics and demographic and lifestyle
      factors was tested to identify specific risk factors that may underlie the shared
      environment of twins. Furthermore, it was tested whether crying without a cause
      and being easily upset were predictive of later internalizing, externalizing and
      attention problems. Crying without a cause yielded a heritability estimate of 60%
      in boys and girls. For easily upset, the heritability was estimated at 43% in
      boys and 31% in girls. The variance explained by shared environment varied
      between 35% and 63%. The correlation between crying without a cause and easily
      upset (r = .36) was explained both by genetic and shared environmental factors.
      Birth cohort, gestational age, socioeconomic status, parental age, parental
      smoking behavior and alcohol use during pregnancy did not explain the shared
      environmental component. Neuroticism of the mother explained a small proportion
      of the additive genetic, but not of the shared environmental effects for easily
      upset. Crying without a cause and being easily upset at age 2 were predictive of
      internalizing, externalizing and attention problems at age 7, with effect sizes
      of .28-.42. A large influence of shared environmental factors on crying without a
      cause and easily upset was detected. Although these effects could be specific to
      these items, we could not explain them by personality characteristics of the
      mother or by demographic and lifestyle factors, and we recognize that these
      effects may reflect other maternal characteristics. A substantial influence of
      genetic factors was found for the two items, which are predictive of later
      behavioral problems.

PMID- 21962131
TI  - Heritability of lung function: a twin study among never-smoking elderly women.
AB  - Most studies on lung function heritability have been conducted in smokers and non
      smokers using cross-sectional study design. Smoking patterns may, however,
      confound the contribution of genetic factors. We investigated heritability of
      forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and
      FEV1/FVC ratio longitudinally, excluding the effects of smoking. A sample of
      never smoking female twins (n = 374), aged 63-76 at baseline, answered health
      questionnaires and attended spirometry in years 2000 and 2003. Bivariate
      structural equation modeling, restricted to adequate spirometry performances
      (baseline n = 339, follow-up n = 252), was used to estimate genetic and
      environmental influences on consecutive measurements of FEV1, FVC, and FEV1/FVC.
      The best-fitting models included additive genetic and non-shared environmental
      effects. Heritability estimates of 32% and 36% for FEV1, 41% and 37% for FVC,
      while 46% and 16% for FEV1/FVC were found at baseline and at follow-up. Genetic
      correlation between FEV1 and FEV1/FVC heritability estimates approached unity,
      whereas correlation between FVC estimates was 0.80. Environmental correlations
      were 0.69 for FEV1, 0.62 for FVC, and 0.07 for FEV1/FVC. In never smokers,
      additive genetic and non-shared environmental effects explain the inter
      individual variations in FEV1, FVC, and FEV1/FVC. One third of the variation in
      FEV1 and FVC is explained by genetic and two thirds by environmental effects.
      Between 2000 and 2003, environmental effects on FEV1/FVC changed, and the
      proportion of variance explained by environmental effects increased remarkably.
      Genetic effects on FEV1 and FEV1/FVC are common to consecutive measurements,
      whereas at follow-up, new genetic factors explained 14% of the observed variance
      in FVC.

PMID- 21962132
TI  - Variation in BMPR1B, TGFRB1 and BMPR2 and control of dizygotic twinning.
AB  - Genes in the TGF9 signaling pathway play important roles in the regulation of
      ovarian follicle growth and ovulation rate. Mutations in three genes in this
      pathway, growth differentiation factor 9 (GDF9), bone morphogenetic protein 15
      (BMP15) and the bone morphogenetic protein receptor B 1 (BMPRB1), influence
      dizygotic (DZ) twinning rates in sheep. To date, only variants in GDF9 and BMP15,
      but not their receptors transforming growth factor beta receptor 1 (TGFBR1), bone
      morphogenetic protein receptor 2 (BMPR2) and BMPR1B, have been investigated with
      respect to their roles in human DZ twinning. We screened for rare and novel
      variants in TGFBR1, BMPR2 and BMPR1B in mothers of dizygotic twins (MODZT) from
      twin-dense families, and assessed association between genotyped and imputed
      variants and DZ twinning in another large sample of MODZT. Three novel variants
      were found: a deep intronic variant in BMPR2, and one intronic and one non
      synonymous exonic variant in BMPRB1 which would result in the replacement of
      glutamine by glutamic acid at amino acid position 294 (p.Gln294Glu). None of
      these variants were predicted to have major impacts on gene function. However,
      the p.Gln294Glu variant changes the same amino acid as a sheep BMPR1B functional
      variant and may have functional consequences. Six BMPR1B variants were marginally
      associated with DZ twinning in the larger case-control sample, but these were no
      longer significant once multiple testing was taken into account. Our results
      suggest that variation in the TGF9 signaling pathway type II receptors has
      limited effects on DZ twinning rates in humans.

PMID- 21962133
TI  - Single nucleotide polymorphism in hsa-mir-196a-2 and breast cancer risk: a case
      control study.
AB  - microRNAs are small, non-coding RNAs that influence gene expression on a post
      transcriptional level. They participate in diverse biological pathways and may
      act as either tumor suppressor genes or oncogenes. As they may have an effect on
      thousands of target mRNAs, single-nucleotide polymorphisms in microRNA genes
      might have major functional consequences, because the microRNA's properties
      and/or maturation may change. miR-196a has been reported to be aberrantly
      expressed in breast cancer tissue. Additionally, the SNP rs11614913 in hsa-mir
      196a-2 has been found to be associated with breast cancer risk in some studies
      although not in others. This study evaluated the association between rs11614913
      and breast cancer risk in a Caucasian case-control cohort in Queensland,
      Australia. Results do not support an association of the tested hsa-mir-196a-2
      polymorphism with breast cancer susceptibility in this cohort. As there is a
      discrepancy between our results and previous findings, it is important to assess
      the role of rs11614913 in breast cancer by further larger studies investigating
      different ethnic groups.

PMID- 21962134
TI  - Polymorphisms in nevus-associated genes MTAP, PLA2G6, and IRF4 and the risk of
      invasive cutaneous melanoma.
AB  - An evolving hypothesis postulates that melanomas may arise through 'nevus
      associated' and 'chronic sun exposure' pathways. We explored this hypothesis by
      examining associations between nevus-associated loci and melanoma risk across
      strata of body site and histological subtype. We genotyped 1028 invasive case
      patients and 1469 controls for variants in methylthioadenosine phosphorylase
      (MTAP), phospholipase A2, group VI (PLA2G6), and Interferon regulatory factor 4
      (IRF4), and compared allelic frequencies globally and by anatomical site and
      histological subtype of melanoma. Odds-ratios (ORs) and 95% confidence intervals
      (CIs) were calculated using classical and multinomial logistic regression models.
      Among controls, MTAP rs10757257, PLA2G6 rs132985 and IRF4 rs12203592 were the
      variants most significantly associated with number of nevi. In adjusted models, a
      significant association was found between MTAP rs10757257 and overall melanoma
      risk (OR = 1.32, 95% CI = 1.14-1.53), with no evidence of heterogeneity across
      sites (Phomogeneity =.52). In contrast, MTAP rs10757257 was associated with
      superficial spreading/nodular melanoma (OR = 1.34, 95% CI = 1.15- 1.57), but not
      with lentigo maligna melanoma (OR = 0.79, 95% CI = 0.46-1.35) (Phomogeneity
      =.06), the subtype associated with chronic sun exposure. Melanoma was
      significantly inversely associated with rs12203592 in children (OR = 0.35, 95% CI
      = 0.16-0.77) and adolescents (OR = 0.61, 95% CI = 0.42-0.91), but not in adults
      (Phomogeneity =.0008). Our results suggest that the relationship between MTAP and
      melanoma is subtype-specific, and that the association between IRF4 and melanoma
      is more evident for cases with a younger age at onset. These findings lend some
      support to the 'divergent pathways' hypothesis and may provide at least one
      candidate gene underlying this model. Further studies are warranted to confirm
      these findings and improve our understanding of these relationships.

PMID- 21962135
TI  - The heritability of premenstrual syndrome.
AB  - We aimed to determine (1) the prevalence of premenstrual syndrome in a sample of
      twins and (2) the relative contribution of genes and environment in premenstrual
      syndrome. A group of 193 subjects inclusive of same gender twins (n = 176) and
      females from opposite sex twin sets (n = 17) entered the study. Heritability
      analysis used same gender twin data only. The probandwise concordance rate for
      the presence or absence of premenstrual syndrome was calculated and the
      heritability of premenstrual syndrome was assessed by a quantitative genetic
      model fitting approach using MX software. The prevalence of premenstrual syndrome
      was 43.0% and 46.8% in monozygotic and dizygotic twins, respectively. The
      probandwise concordance for premenstrual syndrome was higher in monozygotic
      (0.81) than in dizygotic twins (0.67), indicating a strong genetic effect.
      Quantitative genetic modeling found that a model comprising of additive genetic
      (A) and unique environment (E) factors provided the best fit (A: 95%, E: 5%). No
      association was found between premenstrual symptom and the following variables:
      belonging to the opposite gender twin set, birth weight, being breast fed and
      vaccination. These results established a clear genetic influence in premenstrual
      syndrome.

PMID- 21962136
TI  - Genetic and environmental sex differences in mental rotation ability: a Japanese
      twin study.
AB  - Sex differences in mental rotation ability have been observed in many countries.
      A previous study of Finnish participants reported that genetic and environmental
      influences on mental rotation ability differ between sexes. In this study, we
      assessed genetic and environmental influences on variance in mental rotation
      ability in 649 Japanese twins using a mental rotation test. To explain the
      influence of sex on variance in mental rotation ability, we applied genetic
      analysis using the sex limitation model. The following two factors explained
      variance in mental rotation ability: (1) the additive genetic factor, which
      reflects the accumulated small influence of many genes, and (2) the unique
      environmental factor, which is a type of environmental factor that differs
      between co-twins. The shared environmental factor, a type of environmental factor
      common for co-twins, could not explain the variance in mental rotation ability.
      Furthermore, the additive genetic factor was the same between sexes (i.e., not
      qualitative sex differences for the additive genetic factor), indicating that the
      same genes affect mental rotation ability in both sexes. Despite this
      observation, the additive genetic influence was greater in males than in females.
      In contrast, the unique environmental influence was not different between sexes.
      Considering the current results and those of a previous study, the quantitative
      sex difference for the additive genetic influences in mental rotation ability may
      be universal, while the unique environmental differences may depend on the
      characteristics of specific populations.

PMID- 21962137
TI  - Conflict, closeness and comfort: the inter-twin relationship as a risk factor for
      behavioral difficulties.
AB  - BACKGROUND: There is currently little evidence concerning the impact of the inter
      twin relationship on behavioral outcomes and yet the twin relationship is
      frequently hypothesized to be a unique source of psychopathology in twins. The
      current study asked whether the inter-twin relationship is a predictor of
      behavioral difficulties and whether there are zygosity differences in this
      relationship. METHOD: An Australian sample of same sex twins (N = 356, 164 MZ and
      192 DZ) was studied in the year prior to school (Time 1) and again in first year
      of school (Time 2). Associations between twin-relationship and behavior problems
      were examined via path-analysis, and Satorra-Bentler chi-square difference tests
      were used to compare twins across zygosity. RESULTS: Results show that both
      conflict and lower levels of warmth at Time 1 were predictive of hyperactivity
      and conduct disorder at Time 2, but they were not associated with emotional
      difficulties or peer problems. While DZ twins shared less warmth than MZ twins,
      there were no differences in behavior problems. CONCLUSION: Conflict and lower
      levels of warmth in the inter-twin relationship are associated with hyperactivity
      and conduct disorder and may serve as important considerations when making
      decisions regarding class separation at entry to school.

PMID- 21962138
TI  - Early anti-angiogenic proteins expression in amniotic fluid of twin fetuses.
AB  - Multiple pregnancies are thought to be associated with a high incidence of
      perinatal complications such as preterm labor, preeclampsia and low birth weight.
      But the true mechanisms of these obstetric complications are still uncertain. The
      components of amniotic fluid reflect the pathophysiology features of the fetus.
      Amniotic fluid soluble fms-like tyrosine kinase 1(sFLT1), soluble endoglin
      (sENG), and adiponectin reflect the oxidative stress and pro-inflammatory status
      and are associated with preeclampsia and fetal growth restriction. We
      prospectively collected amniotic fluids during amniocentesis from singleton and
      twin pregnancies. Samples were analyzed for levels of sFLT1, sENG, and
      adiponectin by enzyme-linked immunosorbent assay. The levels of sENG and sFLT1
      were significantly increased in twin pregnancies. Adiponectin was not
      significantly different between the two groups. These findings would suggest that
      twin fetuses suffer from more oxidative stress and pro-inflammatory status from
      the early trimesters.

PMID- 21962139
TI  - Perinatal outcome of monochorionic twins with selective IUGR compared with
      uncomplicated monochorionic twins.
AB  - OBJECTIVE: To evaluate the perinatal outcome of MC twins with selective IUGR
      (sIUGR). STUDY DESIGN: A prospective study, which included three groups of MC
      twins: Group A, uncomplicated MC twin pregnancies (n = 91); group B, sIUGR with
      normal umbilical artery Doppler (n = 19); and group C, sIUGR with abnormal
      (absence or reversed EDV) umbilical artery Doppler (n = 18). The latter were
      routinely hospitalized in the high-risk ward under strict surveillance. RESULTS:
      Neonatal outcome of fetuses complicated with sIUGR and normal Doppler was similar
      to controls. Neonates born to pregnancies complicated by sIUGR and abnormal
      Doppler had significantly increased incidence of CNS findings, RDS, NEC, sepsis,
      and neonatal death compared to controls. Adverse outcome in this group was
      independently associated only with gestational age at birth. CONCLUSION: The
      perinatal outcomes of MC twins complicated with sIUGR and normal Doppler are
      similar to uncomplicated MC pregnancies. MC twins with sIUGR and abnormal Doppler
      have reasonable outcomes, yet significantly more neonatal complications compared
      to non-complicated MC twins.

PMID- 21962140
TI  - Is growth-discordance in twins a substantial risk factor in adverse neonatal
      outcomes?
AB  - To evaluate whether growth discordance is an independent risk factor in the
      neonatal outcome of the smaller twin, all medical records of twin pregnancies
      delivered between 26 and 41 weeks during a 5-year period (January 2004-December
      2008) were reviewed. Among the 49 selected twins, weight discordance was 15-20%
      in 7 infants, 21-30% in 16 infants, 31-40% in 16 infants and > 40% in 10 infants.
      No significant differences between the four groups were found with regards to
      obstetric complications and neonatal disease. Occurrence of birthweight below the
      10th percentile and rate of admission to the neonatal intensive care unit
      significantly increased as intra-pair birthweight difference increased (p = .03).
      The > 40% discordant group had a significantly lower gestational age (p = .03),
      lower birthweight (p = .007) and a significantly higher mortality rate (4/10
      versus 3/39 p = .04) in comparison with the other discordant groups. Multiple
      logistic regression analysis showed that birthweight was the single independent
      and consistent factor associated with elevated risks of mortality. For every 250
      g increase in birthweight, the risk for mortality decreased by about 84% [RR
      0.16(CI 0.00-0.70)]. Gestational age was the most reliable predictor for major
      neonatal complications. For every 1-week increase in gestational age a
      significant decreased risk for all outcomes was found. Discordance alone should
      not be considered as a predictor for adverse neonatal outcome. Neonatal outcome
      in discordant twins appears to be related to gestational age and birthweight
      rather than to the degree of discordance.

PMID- 21962141
TI  - Height growth of triplets from birth to 12 years of age in Japan.
AB  - We analyzed the characteristics associated with the growth in height of Japanese
      triplets from birth to 12 years of age. The study included 376 mothers and their
      1,128 triplet children, who were born between 1978 and 2006. Data were collected
      through a mailed questionnaire sent to the mothers asking for information
      recorded in medical records. For these births, data on triplets' length and
      height growth, gestational age, sex, parity, maternal age at delivery, and
      maternal height were obtained from records in the Maternal and Child Health
      Handbooks and records in the school which children receive health check-ups. The
      height deficit of the triplets compared to the general population of Japan
      remained between 2% and 5% until 12 years of age. Moreover, at 12 years of age,
      the differences of height between the general population and triplets were
      approximately -3.6 cm for male and -4.4 cm for female. Maternal height showed the
      strongest contribution to height of triplets from 6 to 12 years of age. In
      conclusion, triplets remain shorter than singletons until 12 years of age.

PMID- 21962142
TI  - Estimation of the contribution of assisted and non-assisted reproductive
      technology fertility treatments to multiple births during the past 30 years in
      Japan: 1979-2008.
AB  - The effect of assisted reproductive technology (ART) and non-ART ovulation
      stimulation fertility treatment on the number and rate of multiple live births
      from 1979-2008 in Japan was estimated using two independent data sources, ART
      statistics and vital statistics. Japanese ART statistics presented by the Japan
      Society of Obstetrics and Gynecology between 1989 and 2008 were gathered and
      reanalyzed. The number and rates of ART between 1984 and 1988 were interpolated
      using an approximation formula, using the values from 1983, when the first ART
      baby was born in Japan, and the 1989-1992 values. The number of ART multiples
      between 1979-1982 was set as equal to zero. The minimum (or maximum) number of
      non-ART iatrogenic multiple births was estimated by subtracting the maximum (or
      minimum) ART multiples from the total iatrogenic multiples, which was estimated
      by vital statistics assuming that spontaneous multiple-birth rates according to
      maternal age class would be constant. There was an overall increase in the non
      ART multiple births during the 30-year period, whereas ART multiples tended to
      increase from 1983 to 2005, and then rapidly decreased thereafter. The number or
      percentage of ART multiples was almost consistently lower than that of non-ART
      multiples. The percentage of non-ART multiples (33%) among the total multiples
      was estimated to be about three times more than the ART multiples (11-12%) in
      2008. Given the medical and social impact of multiple births, it is imperative to
      construct a hospital-based monitoring system for fertility treatments, specially
      non-ART fertility treatments and multiple births.

PMID- 21962143
TI  - Incidence and costs of multifetal pregnancies in Andalusia (2000-2010).
AB  - In the past 50 years the incidence of multiple pregnancies has increased
      dramatically due almost exclusively to two factors: delayed childbearing and
      assisted reproductive techniques. In this paper we analyze the variations in the
      incidence of multiple gestations in Andalusia, one of the biggest administrative
      regions in Spain, over the last decade. Assisted reproduction techniques are very
      often evaluated only in terms of implantation and pregnancy rates per cycle,
      ignoring everything related to complications of multiple births, prematurity or
      economic overload. The rate of twins in Andalusia has increased from 10.9 per
      thousand in 2000 to 16.2 per thousand in 2009. The rate of triplet births has
      also increased in recent years. After a decline in 2003, motivated by
      promulgation of the first Human Assisted Reproduction Law, there was an increase
      after a second law came into effect in 2006. Health care spending attributable to
      the excess of multiple pregnancies reported in the decade 2000-2010 may have been
      much higher than ? 25 million.

PMID- 21962144
TI  - Rare conjoined twins / twin research reviews / twins in the news.

PMID- 21962145
TI  - Resistance of polio to its eradication in Pakistan.
AB  - BACKGROUND: This study is based on EPI (Expanded Program on Immunization)
      immunization surveys and surveillance of polio, its challenges in immunization
      and the way forward to overcome these challenges. METHODS: Several Government
      documents, survey reports and unpublished program documents were studied and
      online search was made to find information on EPI Pakistan. SPSS 16 and Microsoft
      Excel 2007 were used for the statistical analysis. RESULTS: Immunization against
      polio is higher in urban areas as compared to rural areas. Marked variation in
      vaccination has been observed in different provinces of Pakistan in the last
      decade. Secondly 10-20% of the children who have received their first dose of
      trivalent polio vaccine were deprived of their 2nd and 3rd dose because of poor
      performance of EPI and Lack of information about immunization. CONCLUSION: In
      spite of numerous successes, such as the addition of new vaccines and raising
      immunization to over 100% in some areas, EPI is still struggling to reach its
      polio eradication goals. Inadequate service delivery, lack of information about
      immunization and limited number of vaccinators were found to be the key reason
      for poor performance of immunization and for large number of cases reported each
      year due to the deficiency of second and third booster dose.

PMID- 21962146
TI  - Multicore-shell PNIPAm-co-PEGMa microcapsules for cell encapsulation.
AB  - The overall goal of this study was to fabricate multifunctional core-shell
      microcapsules with biological cells encapsulated within the polymer shell.
      Biocompatible temperature responsive microcapsules comprised of silicone oil
      droplets (multicores) and yeast cells embedded in a polymer matrix (shell) were
      prepared using a novel microarray approach. The cross-linked polymer shell and
      silicone multicores were formed in situ via photopolymerization of either poly(N
      isopropylacryamide)(PNIPAm) or PNIPAm, copolymerized with poly(ethylene glycol
      monomethyl ether monomethacrylate) (PEGMa) within the droplets of an oil-in-water
      in-oil double emulsion. An optimized recipe yielded a multicore-shell morphology,
      which was characterized by optical and laser scanning confocal microscopy (LSCM)
      and theoretically confirmed by spreading coefficient calculations. Spreading
      coefficients were calculated from interfacial tension and contact angle
      measurements as well as from the determination of the Hamaker constants and the
      pair potential energies. The effects of the presence of PEGMa, its molecular
      weight (M(n) 300 and 1100 g/mol), and concentration (10, 20, and 30 wt %) were
      also investigated, and they were found not to significantly alter the morphology
      of the microcapsules. They were found, however, to significantly improve the
      viability of the yeast cells, which were encapsulated within PNIPAm-based
      microcapsules by direct incorporation into the monomer solutions, prior to
      polymerization. Under LSCM, the fluorescence staining for live and dead cells
      showed a 30% viability of yeast cells entrapped within the PNIPAm matrix after 45
      min of photopolymerization, but an improvement to 60% viability in the presence
      of PEGMa. The thermoresponsive behavior of the microcapsules allows the silicone
      oil cores to be irreversibly ejected, and so the role of the silicone oil is 2
      fold. It facilitates multifunctionality in the microcapsule by first being used
      as a template to obtain the desired core-shell morphology, and second it can act
      as an encapsulant for oil-soluble drugs. It was shown that the encapsulated oil
      droplets were expelled above the volume phase transition temperature of the
      polymer, while the collapsed microcapsule remained intact. When these
      microcapsules were reswollen with an aqueous solution, it was observed that the
      hollow compartments refilled. In principle, these hollow-core microcapsules could
      then be filled with water-soluble drugs that could be delivered in vivo in
      response to temperature.

PMID- 21962147
TI  - Structure-activity studies of diazabicyclo[3.3.0]octane-substituted pyrazines and
      pyridines as potent alpha4beta2 nicotinic acetylcholine receptor ligands.
AB  - A series of diazabicyclo[3.3.0]octane substituted pyridines and pyrazines was
      synthesized and characterized at the alpha4beta2 neuronal nicotinic acetylcholine
      receptor (nAChR). The compounds were designed to mimic the profile of ABT-089,
      high affinity binding ligand for the alpha4beta2 nAChR, with limited agonist
      activity. Carboxamide derivatives of 3-(diazabicyclo[3.3.0]octane)-substituted
      pyridines or 2-(diazabicyclo[3.3.0]octane)-substituted pyrazines were found to
      have the desired binding and activity profile. The structure-activity
      relationship of these compounds is presented.

PMID- 21962148
TI  - Primitive neuroectodermal tumor of the cervix: a case report.
AB  - INTRODUCTION: Peripheral primitive neuroectodermal tumor of the cervix uteri is
      extremely rare. Between 1987 and 2010, there were only nine cases reported in the
      English literature, with considerably different management policies. CASE
      PRESENTATION: A 45-year-old Iranian woman presented to our facility with a
      primitive neuroectodermal tumor of the cervix uteri. Her clinical stage IB2 tumor
      was treated successfully with chemotherapy. Our patient underwent radical
      hysterectomy. There was no trace of the tumor after four years of follow-up.
      CONCLUSIONS: According to current knowledge, primitive neuroectodermal tumors
      belong to the Ewing's sarcoma family, and the improvement of treatment outcome in
      our patient was due to dose-intensive neoadjuvant chemotherapy, surgery and
      consolidation chemotherapy in accordance with the protocol for bony Ewing's
      sarcoma.

PMID- 21962149
TI  - The predictive value of leukocyte parameters for hypertensive disorders of
      pregnancy in south China.
AB  - OBJECTIVE: To evaluate the predictive values of the leukocyte parameters for
      hypertensive disorders in pregnancy (HDP). METHODS: A total of 523 HDP patients
      and 853 normal pregnancies were included in the present study. The leukocyte
      parameters in different stages of pregnancy were compared among the groups, and
      the efficiency of clinical diagnosis was calculated to analyze the predictive
      value of these parameters to HDP. RESULTS: Women with HDP presented significantly
      higher leukocyte parameters in the second trimester and significantly lower
      values in the last trimester as compared to the normal gravidas. An evident
      increase of several parameters was observed preceding the clinical syndromes of
      HDP; and the odds ratio of increased neutrophil (NEU) and basophil (Baso) for
      predicting HDP were 1.02 and 1.16 (p < 0.01), respectively. The sensitivity of
      NEU was 71.95% when it was higher than 6.12 * 10(9)/L, and the specificity of
      Baso was 71.01% when it was higher than 0.053 * 10(9)/L for the prediction of HDP
      in 13-20 weeks. CONCLUSION: The NEU and Baso are helpful for predicting HDP
      during the presymptom period.

PMID- 21962150
TI  - Colleague interactions and new drug prescribing behavior: the case of the initial
      prescription of antidepressants in Taiwanese medical centers.
AB  - This research explores the social factors influencing hospital physicians'
      initial adoption of duloxetine hydrochloride, with a focus on colleague
      interactions. The study analyzes archival data compiled by the National Health
      Insurance Research Database of Taiwan to examine how the prescribing decisions
      made by psychiatrists' colleagues influence the likelihood of the psychiatrists'
      initial prescription. The results show that the adoption ratio of a physician's
      colleagues in a medical center is positively associated with the likelihood of a
      physician's adoption of the new drug. Specifically, colleague groups with similar
      and longer tenure as well as similar and older age have significantly positive
      effects. Colleague groups with the same and different gender also have positive
      effects. In summary, tenure and age, rather than gender, are vital sources of
      heterogeneous colleague interactions.

PMID- 21962151
TI  - Where do pharmaceuticals on the market originate? An analysis of the informal
      drug supply in Cotonou, Benin.
AB  - This anthropological study, conducted in Cotonou, Benin between 2005 and 2007,
      investigates the informal pharmaceuticals market. It was carried out through a
      long-term participant observation of informal vendors and semi-directive and
      unstructured interviews. A classification of products sold in the informal market
      was developed. The fact that a high percentage of them come from Anglophone
      countries near Benin (Nigeria and Ghana) led to a comparison of the sources of
      pharmaceutical supply in these three countries as well as their current
      legislation regarding pharmaceutical distribution. Our study results highlight a
      new understanding of the phenomenon of the informal market. Nigeria and Ghana
      rely on a liberal pharmaceutical distribution system with little intervention
      from public authorities. Conversely, the government maintains considerable
      influence over pharmaceutical distribution in Benin. Hence, the differences
      between these three countries in terms of variety of supply sources and
      flexibility of access to drugs are understood through an investigation of Benin's
      informal market. Therefore, it appears that beyond issues concerning the quality
      of the pharmaceuticals, this phenomenon illustrates a kind of liberalization of
      pharmaceutical distribution and the ensuing public health issues.

PMID- 21962152
TI  - Family psychosocial characteristics influencing criminal behaviour and mortality-
      possible mediating factors: a longitudinal study of male and female subjects in
      the Stockholm Birth Cohort.
AB  - BACKGROUND: Family psychosocial characteristics in childhood have been associated
      with children's development into criminal behaviour and mortality. This study
      explored these possible relationships and examined alcohol and/or drug use and
      mental problems as possible mediating factors, highlighting gender-specific
      patterns. METHODS: Data from Swedish subjects born in 1953 (n = 14,294) from the
      Stockholm Birth Cohort study were examined. Several indicators of adverse family
      factors and individual problems were included in the present study. The
      information was derived from various data sources, covering different periods.
      Gender-specific associations with incidence of criminality (1966-1980) and
      mortality (1981-2009) were analysed using logistic regression. Furthermore, the
      population attributable fraction (PAF) was calculated for all variables in the
      fully adjusted models which were positively related to the outcome. RESULTS:
      Overall incidence of criminality and mortality was (m/f 32.3/6.6) and (m/f
      6.1/3.5), respectively. The results showed that all aspects of family
      psychosocial and individual problems studied were associated with criminality for
      both genders. Among males, individual problems seemed to partly mediate these
      relations, but the associations remained statistically significant.
      Interestingly, the PAF analysis revealed a reduction in criminality of 17.5% when
      individual problems with alcohol and/or drug use were considered. Among females,
      a significant impact of alcohol and/or drug use on the association between family
      psychosocial characteristics and subsequent criminality was obtained. Inclusion
      of father's occupational class only somewhat reduced the estimates for the
      genders. Concerning male mortality, father's alcohol abuse was significantly
      related to an increased risk. When individual criminality was accounted for, the
      association was substantially reduced but remained statistically significant.
      Among females, when adjusting for family psychosocial factors, only the
      association between parents' mental problems and females' mortality was
      significant. None of the individual problem variables managed to explain this
      association. CONCLUSIONS: Family psychosocial characteristics were associated
      with both subsequent criminal behaviour and mortality. These connections were
      partly explained by individual risk factors, especially by alcohol and/or drug
      use. The practical implications of the findings point to the importance of
      addressing the individual's alcohol and/or drug use in reducing criminal
      behaviour, which would also lower the mortality rates.

PMID- 21962153
TI  - The prognostic roles of initial glucose level and functional outcomes in patients
      with ischemic stroke: difference between diabetic and nondiabetic patients.
AB  - PURPOSE: To identify the prognostic roles of initial glucose level in the
      emergency department among patients with acute ischemic stroke, and to evaluate
      whether or not the impact varied with diabetes. METHODS: A total of 774 first
      ever ischemic stroke patients admitted to the emergency department of a tertiary
      hospital in Taiwan. Participants were stratified into tertiles by initial glucose
      level in the emergency department. The Barthel Index (BI) and modified Rankin
      Scale (mRS) were used to assess functional outcome 3 months after the ischemic
      stroke. RESULTS: Initial glucose level was significantly associated with
      functional outcome 3 months after ischemic stroke. Compared with the 1st tertile,
      adjusted odds ratios for 2nd and 3rd tertiles of initial glucose level were 1.84
      (95% confidence interval [CI], 1.15-2.95) and 4.57 (95% CI, 2.87-7.29), for BI of
      less than 60, 2.07 (95% CI, 1.28-3.36) and 4.45 (95% CI, 2.76-7.18) for mRS score
      of >2. The association was apparent among the nondiabetic stroke patients
      compared with diabetic patients. CONCLUSIONS: A positive association was found
      between initial glucose level and poor functional outcome at 3 months in patients
      with acute ischemic stroke, particularly among nondiabetic patients.

PMID- 21962154
TI  - Pharmacokinetics and biodistribution of human serum albumin-TIMP-2 fusion protein
      using near-infrared optical imaging.
AB  - PURPOSE: TIMP-2 has been studied as an attractive cancer therapeutic candidate,
      and a TIMP-2 fusion protein (HSA/TIMP-2) displayed effective anticancer activity,
      despite a lack of information about its pharmacokinetics (PK) and
      biodistribution. The purpose of this work was to assess the PK and
      biodistribution of HSA/TIMP-2 as well as to quantify accumulated HSA/TIMP-2 in
      tumors. METHODS: Cy5.5 near-infrared (NIR) fluorescence was conjugated to the
      HSA/TIMP-2 protein (Cy5.5-HSA/TIMP-2) for monitoring spatio-temporal changes in
      vivo. For PK and biodistribution analysis, 0.2 MUg/g body weight of Cy5.5
      HSA/TIMP-2 was injected into MAT-LyLu prostate tumor xenografts, which were then
      imaged using an IVIS-200 optical imaging system. To quantify the accumulated
      HSA/TIMP-2 in tumors, we introduced a standard curve with depth-corrected
      fluorescence measurement. RESULTS: In the vascular tube formation assay with
      human umbilical vein endothelial cells (HUVECs), Cy5.5-HSA/TIMP-2 showed an
      antiangiogenic effect. In prostate cancer xenografts, Cy5.5-HSA/TIMP-2 exhibited
      a prolongation of blood half-life to 19.6 h and relatively preferential
      distribution to the tumor. The amount of tumor-accumulated Cy5.5-HSA/TIMP-2 was
      calculated to be 4.5 +/- 0.5 ng/g body weight at 2 days, representing 2.25 +/-
      0.25% of the initial dose. CONCLUSIONS: We evaluated the pharmacokinetic profile
      and biodistribution of HSA/TIMP-2 with favorable results, providing new
      information for more effective approaches to cancer therapeutics using HSA/TIMP
      2. Additionally, real-time in vivo fluorescence imaging analysis using a depth
      corrected standard curve may serve as a platform to quantify biodistributed drug
      in anticancer therapeutic studies.

PMID- 21962158
TI  - Phase-separation-induced single-crystal morphology in poly(L-lactic acid) blended
      with poly(1,4-butylene adipate) at specific composition.
AB  - The single-crystal morphology of poly(L-lactic acid) (PLLA) in blending with
      poly(butylene adipate) (PBA) in PLLA/PBA blends was for the first time reported
      in melt crystallization. At crystallization temperature (T(c)) = 110  degrees C,
      by adding 30 wt % PBA into PLLA, the lamellae exhibit six-stalk dendrites with
      single-crystal packing. Phase separation and crystallization took place
      simultaneously at T(c) = 110  degrees C in PLLA/PBA (70/30) blend, leading to
      discrete PBA domains and continuous PLLA domains. For PLLA/PBA (70/30) blend, all
      PBA were rejected from the growth front of PLLA crystals, expelled, and
      crystallized at ambient temperature as ring-banded PBA spherulites inside the
      discrete domains only, resulting in a favorable environment for formation of PLLA
      single crystals in the continuous domain. Atomic force microscopy (AFM)
      observation on individual crystallites reveals that lozenge-shaped single
      crystals were packed with a clockwise spiral pattern, stacked in 1-3 layers, and
      these lozenge-shaped crystals are aligned six hexasected directions into
      hexastalk dendrites with occasional side branches that are also aligned at 60
      degrees  to main branches. The monolamellar thickness of lozenge-shaped single
      crystals was measured to be about 13-34 nm, and the dimension is about 0.8-3 MUm
      along the short axis and 1.6-5 MUm along the long axis. Typically, three layers
      of single crystals are stacked one on another; the lozenge crystals on the bottom
      layer are about twice as large as those on the top layer, forming a pyramid shape
      in the depth direction. Formation mechanisms of single crystals in melt
      crystallized PLLA/PBA blend from 700 nm film thickness are discussed in
      correlation with exact phase separation at 30 wt % PBA.

PMID- 21962160
TI  - Cavernous malformations.

PMID- 21962159
TI  - Gamma Knife surgery for nonvestibular schwannomas: radiological and clinical
      outcomes.
AB  - OBJECT: Most intracranial schwannomas arise from cranial nerve (CN) VIII.
      Stereotactic radiosurgery is a mainstay of treatment for vestibular schwannomas.
      Intracranial schwannomas arising from other CNs are much less common. We evaluate
      the efficacy of Gamma Knife surgery on nonvestibular schwannomas including
      trigeminal, hypoglossal, abducent, facial, trochlear, oculomotor,
      glossopharyngeal, and jugular foramen tumors. METHODS: Thirty-six patients with
      nonvestibular schwannomas were treated at the University of Virginia Gamma Knife
      center from 1989 to 2008. The median patient age was 48 years (mean 45.6 years,
      range 10-72 years). Schwannomas arose from the following CNs: CN III (in 1
      patient), CN IV (in 1), CN V (in 25), CN VI (in 2), CN VII (in 1), CN IX (in 1),
      and CN XII (in 3). In 2 patients, tumors arose from the jugular foramen. The
      median tumor volume was 2.9 cm(3) (mean 3.3 cm(3), range 0.07-8.8 cm(3)). The
      median margin dose was 13.5 Gy (range 9.3-20 Gy); the median maximum dose was 30
      Gy (range 21.7-50.0 Gy). RESULTS: The mean and median follow-up times of 36
      patients were 54 and 37 months, respectively (range 2-180 months). At the last
      radiological follow-up, the tumor size had decreased in 20 patients, remained
      stable in 9 patients, and increased in 7 patients. The 2-year actuarial
      progression-free survival was 91%. Higher maximum dose was statistically related
      to tumor control (p = 0.027). Thirty-three patients had adequate clinical follow
      up. Among them, 21 patients had improvement in their presenting symptoms, 8
      patients were stable after treatment with no worsening of their presenting
      symptoms, 2 patients developed new symptoms, and 1 patient experienced symptom
      deterioration. Notably, 1 patient with neurofibromatosis Type 2 developed new
      symptoms that were unrelated to the tumor treated with Gamma Knife surgery.
      CONCLUSIONS: Gamma Knife surgery is a reasonably effective treatment option for
      patients with nonvestibular schwannomas. Patients require careful follow-up for
      tumor progression and signs of neurological deterioration.

PMID- 21962161
TI  - The history of pituitary surgery for Cushing disease.
AB  - Although he never performed a pituitary operation for the disease, Harvey Cushing
      was the first to describe and treat patients with Cushing disease (CD). Other
      surgeons at the time were reluctant to operate on the pituitary due to the normal
      sella on skull radiographs in CD and the unclear etiology of the disorder. To
      better define and understand factors influencing the history of pituitary surgery
      for CD, the authors analyzed historical texts related to CD biology, diagnosis,
      and treatment. Cushing's monograph on basophilic pituitary adenomas and cortisol
      excess appeared in 1932. One year later in 1933, Alfred Pattison performed the
      first successful pituitary operation for CD by implanting radon seeds in the
      sella. Resection of a pituitary adenoma for CD was attempted 1 month later in
      1933 by Howard Naffziger, resulting in only transient improvement that
      corresponded to the lack of tumor in the resected tissue. Soon thereafter, Susman
      in 1935 and Costello in 1936 described pituitary basophilic adenomas at autopsy
      in patients without premorbid endocrinopathy. They concluded that the adrenal
      gland was the cause of CD, which resulted in a 3-decade abandonment of pituitary
      surgery for CD. Jules Hardy in 1963 used the operating microscope to perform the
      first selective removal of an adrenocorticotropic hormone (ACTH)-secreting
      microadenoma, which established a pituitary cause and defined the modern
      treatment of CD. Subsequent reports by Hardy, Laws, and Wilson resulted in
      widespread acceptance of pituitary surgery for CD. Initial reluctance to operate
      on the pituitary for CD was multifaceted and included general uncertainty
      surrounding the etiology of Cushing syndrome as well as a lack of early surgical
      success, both due to the small size of ACTH-secreting adenomas. Selective removal
      of ACTH-secreting adenomas identified the source of CD and ended the delay in
      acceptance of pituitary surgery for CD.

PMID- 21962162
TI  - Improvement in executive function after unilateral carotid artery stenting for
      severe asymptomatic stenosis.
AB  - OBJECT: Executive functions are crucial for organizing and integrating cognitive
      processes. While some studies have assessed the effect of carotid artery stenting
      (CAS) on cognitive functioning, results have been conflicting. The object of this
      study was to assess the effect of CAS on cognitive status, with special interest
      on executive functions, among patients with severe asymptomatic internal carotid
      artery (ICA) stenosis. METHODS: The authors prospectively assessed the
      neuropsychological status of 20 patients with unilateral asymptomatic
      extracranial ICA stenosis of 60% or more by using a comprehensive assessment
      battery focused on executive functions before and after CAS. Individual raw
      scores on neuropsychological tests were converted into z scores by normalizing
      for age, sex, and years of education. The authors compared baseline and 3-month
      postoperative neuropsychological scores by using Wilcoxon signed-rank tests.
      RESULTS: The mean preoperative cognitive performance was within normal ranges on
      all variables. All patients underwent a successful CAS procedure. Executive
      function scores improved after CAS, relative to baseline performance as follows:
      set shifting (Trail-Making Test Part B: -0.75 +/- 1.43 vs -1.2 +/- 1.48, p =
      0.003) and processing speed (digit symbol coding: -0.66 +/- 0.85 vs -0.97 +/-
      0.82, p = 0.035; and symbol search: -0.24 +/- 1.32 vs -0.56 +/- 0.77, p = 0.049).
      The benefit of CAS for working memory was marginally significant (digit span
      backward: -0.41 +/- 0.61 vs -0.58 +/- 0.76, p = 0.052). Both verbal (immediate
      Rey Auditory Verbal Learning Test: 0.35 +/- 1.04 vs -0.22 +/- 0.82, p = 0.011)
      and visual (delayed Rey-Osterrieth Complex Figure: 0.27 +/- 1.26 vs -0.22 +/-
      1.01, p = 0.024) memory improved after CAS. CONCLUSIONS: The authors found a
      beneficial effect on executive function and memory 3 months after CAS among their
      prospective cohort of consecutive patients with unilateral and asymptomatic ICA
      stenosis of 60% or more.

PMID- 21962163
TI  - Outcomes of Gamma Knife surgery for trigeminal neuralgia secondary to
      vertebrobasilar ectasia.
AB  - OBJECT: Vertebrobasilar ectasia (VBE) is an unusual cause of trigeminal neuralgia
      (TN). The surgical options for patients with medically refractory pain include
      percutaneous or microsurgical rhizotomy and microvascular decompression (MVD).
      All such procedures can be technically challenging. This report evaluates the
      response to a minimally invasive procedure, Gamma Knife surgery (GKS), in
      patients with TN associated with severe vascular compression caused by VBE.
      METHODS: Twenty patients underwent GKS for medically refractory TN associated
      with VBE. The median patient age was 74 years (range 48-95 years). Prior surgical
      procedures had failed in 11 patients (55%). In 9 patients (45%), GKS was the
      first procedure they had undergone. The median target dose for GKS was 80 Gy
      (range 75-85 Gy). The median follow-up was 29 months (range 8-123 months) after
      GKS. The treatment outcomes were compared with 80 case-matched controls who
      underwent GKS for TN not associated with VBE. RESULTS: Intraoperative MR imaging
      or CT scanning revealed VBE that deformed the brainstem in 50% of patients. The
      trigeminal nerve was displaced in cephalad or lateral planes in 60%. In 4
      patients (20%), the authors could identify only the distal cisternal component of
      the trigeminal nerve as it entered into the Meckel cave. After GKS, 15 patients
      (75%) achieved initial pain relief that was adequate or better, with or without
      medication (Barrow Neurological Institute [BNI] pain scale, Grades I-IIIb). The
      median time until pain relief was 5 weeks (range 1 day-6 months). Twelve patients
      (60%) with initial pain relief reported recurrent pain between 3 and 43 months
      after GKS (median 12 months). Pain relief was maintained in 53% at 1 year, 38% at
      2 years, and 10% at 5 years. Some degree of facial sensory dysfunction occurred
      in 10% of patients. Eventually, 14 (70%) of the 20 patients underwent an
      additional surgical procedure including repeat GKS, percutaneous procedure, or
      MVD at a median of 14 months (range 5-50 months) after the initial GKS. At the
      last follow-up, 15 patients (75%) had satisfactory pain control (BNI Grades I
      IIIb), but 5 patients (25%) continued to have unsatisfactory pain control (BNI
      Grade IV or V). Compared with patients without VBE, patients with VBE were much
      less likely to have initial (p = 0.025) or lasting (p = 0.006) pain relief.
      CONCLUSIONS: Pain control rates of GKS in patients with TN associated with VBE
      were inferior to those of patients without VBE. Multimodality surgical or medical
      management strategies were required in most patients with VBE.

PMID- 21962164
TI  - Cerebral cavernous malformations: from genes to proteins to disease.
AB  - Over the past half century molecular biology has led to great advances in our
      understanding of angio- and vasculogenesis and in the treatment of malformations
      resulting from these processes gone awry. Given their sporadic and familial
      distribution, their developmental and pathological link to capillary
      telangiectasias, and their observed chromosomal abnormalities, cerebral cavernous
      malformations (CCMs) are regarded as akin to cancerous growths. Although the
      exact pathological mechanisms involved in the formation of CCMs are still not
      well understood, the identification of 3 genetic loci has begun to shed light on
      key developmental pathways involved in CCM pathogenesis. Cavernous malformations
      can occur sporadically or in an autosomal dominant fashion. Familial forms of
      CCMs have been attributed to mutations at 3 different loci implicated in
      regulating important processes such as proliferation and differentiation of
      angiogenic precursors and members of the apoptotic machinery. These processes are
      important for the generation, maintenance, and pruning of every vessel in the
      body. In this review the authors highlight the latest discoveries pertaining to
      the molecular genetics of CCMs, highlighting potential new therapeutic targets
      for the treatment of these lesions.

PMID- 21962165
TI  - Evoked potentials.

PMID- 21962171
TI  - A redox-gated slow-fast-stop molecular rotor.
AB  - A pentiptycene-derived p-phenylenediamine mimics a molecular double-rotor system
      that displays redox-dependent rotation rates for the amino rotors about the
      pentiptycene-amine C-N bond. The rotation is accelerated in the radical cation
      state but stopped in the di(radical cation) state. Electronic interplay of the
      two rotors is also discussed.

PMID- 21962172
TI  - Conversion to lanthanum carbonate monotherapy effectively controls serum
      phosphorus with a reduced tablet burden: a multicenter open-label study.
AB  - BACKGROUND: Lanthanum carbonate (FOSRENOL(r)) is an effective, well-tolerated
      phosphate binder. The ability of lanthanum to reduce serum phosphorus levels to
      <=5.5 mg/dL in patients with end-stage renal disease (ESRD) was assessed in a
      clinical practice setting. METHODS: A 16-week, phase IV study enrolled 2763
      patients at 223 US sites to evaluate the efficacy of lanthanum carbonate in
      controlling serum phosphorus in patients with ESRD, and patient and physician
      satisfaction with, and preference for, lanthanum carbonate after conversion from
      other phosphate-binder medications. Patients received lanthanum carbonate
      prescriptions from physicians. These prescriptions were filled at local
      pharmacies rather than obtaining medication at the clinical trial site. Changes
      from serum phosphorus baseline values were analyzed using paired t tests. Patient
      and physician preferences for lanthanum carbonate versus previous medications
      were assessed using binomial proportion tests. Satisfaction was analyzed using
      the McNemar test. Daily dose, tablet burden, and laboratory values including
      albumin-adjusted serum calcium, calcium * phosphorus product, and parathyroid
      hormone levels were secondary endpoints. RESULTS: Serum phosphorus control (<=5.5
      mg/dL) was effectively maintained in patients converting to lanthanum carbonate
      monotherapy; 41.6% of patients had controlled serum phosphate levels at 16 weeks.
      Patients and physicians expressed markedly higher satisfaction with lanthanum
      carbonate, and preferred lanthanum carbonate over previous medication. There were
      significant reductions in daily dose and daily tablet burden after conversion to
      lanthanum carbonate. CONCLUSIONS: Serum phosphorus levels were effectively
      maintained in patients converted from other phosphate-binder medications to
      lanthanum carbonate, with increased satisfaction and reduced tablet burden. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT0016012.

PMID- 21962173
TI  - A bioorthogonal quadricyclane ligation.
AB  - New additions to the bioorthogonal chemistry compendium can advance biological
      research by enabling multiplexed analysis of biomolecules in complex systems.
      Here we introduce the quadricyclane ligation, a new bioorthogonal reaction
      between the highly strained hydrocarbon quadricyclane and Ni bis(dithiolene)
      reagents. This reaction has a second-order rate constant of 0.25 M(-1) s(-1), on
      par with fast bioorthogonal reactions of azides, and proceeds readily in aqueous
      environments. Ni bis(dithiolene) probes selectively labeled quadricyclane
      modified bovine serum albumin, even in the presence of cell lysate. We have
      demonstrated that the quadricyclane ligation is compatible with, and orthogonal
      to, strain-promoted azide-alkyne cycloaddition and oxime ligation chemistries by
      performing all three reactions in one pot on differentially functionalized
      protein substrates. The quadricyclane ligation joins a small but growing list of
      tools for the selective covalent modification of biomolecules.

PMID- 21962174
TI  - Sales of antidepressants, suicides and hospital admissions for depression in
      Veneto Region, Italy, from 2000 to 2005: an ecological study.
AB  - BACKGROUND: Increased prescription of antidepressants has been consistently
      associated with a decrease in suicide rates in several countries. The aim of this
      study is to explore antidepressant consumption, suicide rates and admission for
      depression in the Veneto Region, Italy, in order to see whether the same pattern
      could be detected. METHODS: Data from the Italian Ministry of Health (admissions
      for depression), the Pharmacy Service of a Local Health Unit (antidepressant
      prescribing) and from the Epidemiological System of the Veneto region (suicide
      rates) were collected from 2000 to 2005 for the Veneto region. RESULTS: Suicide
      rates did not show any marked increase but were stable in males and females.
      Antidepressant prescribing increased exponentially over the period examined,
      whilst admissions for depression markedly decreased. The trend for an exponential
      increase in antidepressant prescribing in the Veneto region is shared with other
      countries and locales. CONCLUSIONS: It is possible that the increase in
      antidepressant prescribing might be associated with earlier treatment of
      depression, thus decreasing the likelihood of aggravation of depression.

PMID- 21962175
TI  - Transcriptome profiling of Pinus radiata juvenile wood with contrasting stiffness
      identifies putative candidate genes involved in microfibril orientation and cell
      wall mechanics.
AB  - BACKGROUND: The mechanical properties of wood are largely determined by the
      orientation of cellulose microfibrils in secondary cell walls. Several genes and
      their allelic variants have previously been found to affect microfibril angle
      (MFA) and wood stiffness; however, the molecular mechanisms controlling
      microfibril orientation and mechanical strength are largely uncharacterised. In
      the present study, cDNA microarrays were used to compare gene expression in
      developing xylem with contrasting stiffness and MFA in juvenile Pinus radiata
      trees in order to gain further insights into the molecular mechanisms underlying
      microfibril orientation and cell wall mechanics. RESULTS: Juvenile radiata pine
      trees with higher stiffness (HS) had lower MFA in the earlywood and latewood of
      each ring compared to low stiffness (LS) trees. Approximately 3.4 to 14.5% out of
      3, 320 xylem unigenes on cDNA microarrays were differentially regulated in
      juvenile wood with contrasting stiffness and MFA. Greater variation in MFA and
      stiffness was observed in earlywood compared to latewood, suggesting earlywood
      contributes most to differences in stiffness; however, 3-4 times more genes were
      differentially regulated in latewood than in earlywood. A total of 108 xylem
      unigenes were differentially regulated in juvenile wood with HS and LS in at
      least two seasons, including 43 unigenes with unknown functions. Many genes
      involved in cytoskeleton development and secondary wall formation (cellulose and
      lignin biosynthesis) were preferentially transcribed in wood with HS and low MFA.
      In contrast, several genes involved in cell division and primary wall synthesis
      were more abundantly transcribed in LS wood with high MFA. CONCLUSIONS:
      Microarray expression profiles in Pinus radiata juvenile wood with contrasting
      stiffness has shed more light on the transcriptional control of microfibril
      orientation and the mechanical properties of wood. The identified candidate genes
      provide an invaluable resource for further gene function and association genetics
      studies aimed at deepening our understanding of cell wall biomechanics with a
      view to improving the mechanical properties of wood.

PMID- 21962176
TI  - Spatial epidemiology of hospital-diagnosed brucellosis in Kampala, Uganda.
AB  - BACKGROUND: A retrospective case-control study was undertaken to examine the
      spatial risk factors for human brucellosis in Kampala, Uganda. METHODS:
      Information on age, sex and month of diagnosis was derived from records from
      plate agglutination tests undertaken at Mulago Hospital, Kampala. Information on
      Parishes (LC2s) where patients reside was sourced from the outpatient
      registration book. In-patient fracture cases were selected for use as controls
      using 1:1 matching based on the age, sex and month of diagnosis. The locations of
      cases and controls were obtained by calculating Cartesian coordinates of the
      centroids of Parish level (LC2) polygons and a spatial scan statistic was applied
      to test for disease clustering. Parishes were classified according to the level
      of urbanization as urban, peri-urban or rural. RESULTS: Significantly more
      females than males were found to show sero-positivity for brucellosis when
      compared with the sex ratio of total outpatients, in addition female brucellosis
      patients were found to be significantly older than the male patients. Spatial
      clustering of brucellosis cases was observed including around Mulago Hospital
      (radius = 6.8 km, p = 0.001). The influence of proximity to the hospital that was
      observed for brucellosis cases was not significantly different from that observed
      in the controls. The disease cluster was confounded by the different catchment
      areas between cases and controls. The level of urbanization was not associated
      with the incidence of brucellosis but living in a slum area was a significant
      risk factor among urban dwellers (odds ratio 1.97, 95% CI: 1.10-3.61).
      CONCLUSIONS: Being female was observed to be a risk factor for brucellosis sero
      positvity and among urban dwellers, living in slum areas was also a risk factor
      although the overall risk was not different among urban, peri-urban and rural
      areas of the Kampala economic zone.

PMID- 21962177
TI  - Assembled monolayers of hydrophilic particles on water surfaces.
AB  - A facile and quick approach to prepare self-assembled monolayers of water
      dispersible particles on the water surface is presented. Particle suspensions in
      alcohols were dropped on a water reservoir to form long-range ordered monolayers
      of various particles, including spherical solid particles, soft hydrogel
      particles, metal nanoparticles, quantum dots, nanowires, single-wall carbon
      nanotubes (SWCNTs), nanoplates, and nanosheets. A systematic study was conducted
      on the variables affecting the monolayer assembly: the solubility parameter of
      spreading solvents, particle concentration, zeta potential of the particles in
      the suspension, surface tension of the water phase, hardness of the particles,
      and addition of a salt in the suspension. This method requires no hydrophobic
      surface treatment of the particles, which is useful to exploit these monolayer
      films without changing the native properties of the particles. The study
      highlights a quick 2D colloidal assembly without cracks in the wafer scale as
      well as transparent conductive thin films made of SWCNTs and graphenes.

PMID- 21962178
TI  - An analytical procedure for the determination of aluminum used in antiperspirants
      on human skin in FranzTM diffusion cell.
AB  - A local case report of hyperaluminemia (aluminum concentration: 3.88 umol/L) in a
      woman using an aluminum-containing antiperspirant for 4 years raises the question
      of possible transdermal uptake of aluminum salt as a future public health
      problem. Prior to studying the transdermal uptake of three commercialized
      cosmetic formulas, an analytical assay of aluminum (Al) in chlorohydrate form
      (ACH) by Zeeman Electrothermal Atomic Absorption Spectrophotometer (ZEAAS) in a
      clean room was optimized and validated. This analysis was performed with
      different media on human skin using a Franz(TM) diffusion cell. The detection and
      quantification limits were set at <= 3 ug/L. Precision analysis as within-run (n
      = 12) and between-run (n = 15-68 days) yield CV <= 6%. The high analytic
      sensitivity (2-3 ug/L) and low variability should allow an in vitro study of the
      transdermal uptake of ACH.

PMID- 21962180
TI  - It is time to transform our health care system.

PMID- 21962179
TI  - Correlation between maternal milk and infant serum levels of chlorinated
      pesticides (CP) and the impact of elevated CP on bleeding tendency and immune
      status in some infants in Egypt.
AB  - Chlorinated pesticides (CP) are environmentally persistent pollutants that
      (prenatally through the placenta and post-natally via breastfeeding) are
      transferred from mother to child. Considering the significant bleeding tendency
      noted in infants of CP-intoxicated mothers in Egypt, this study aimed to
      investigate any correlation between levels of these xenobiotics in mothers' milk
      and bleeding tendencies of their infants, as well as a possible role of any
      related immunosuppression in this phenomenon. This study examined 180 newborns
      presenting with altered bleeding tendencies and their mothers, and 180 normal
      newborns and their mothers (serving as a controls), selected from the
      Breastfeeding Unit, Center for Social and Preventive Medicine at the Cairo
      University Pediatric Hospital. Chlorinated pesticides (e.g.,
      hexachlorocyclohexane, DDT, hepta-chloroepoxide, alpha- and beta-endosulfan,
      aldrin, endrin, dieldrin) levels and their derivatives were measured in mothers'
      milk as well as in serum of neonates using gas chromatography/high resolution
      mass spectrometry. To link bleeding tendency with lactational intoxication of
      neonates by CP, newborns' blood was assessed for: platelet count, bleeding and
      prothrombin time, liver enzymes, Vitamin K, TNFalpha, and IL-10. Breast milk CP
      levels were associated with a higher incidence of bleeding in infants.
      Interference with the coagulation cascade was supported by changes in prothrombin
      time (prolonged), platelet counts (decreased), liver enzymes (increased), and
      serum vitamin K concentrations (decreased). Moreover, the significant decrease in
      WBC count and lymphocytes added to depressed cytokine secretion, i.e., TNFalpha
      and IL-10, suggested an organochlorine-induced immunotoxicity in infants
      developmentally exposed to the agents. We conclude that maternal transfer of CP,
      via breastfeeding or across the placenta, was sufficient to achieve similar CP
      levels in the serum of their infants; this correlated with a manifesting of
      altered bleeding tendencies and perturbed cytokine biology in these infants.

PMID- 21962182
TI  - The fusiform skin excision: one recipe for success.
AB  - The fusiform skin excision is commonly performed by dermatologists. This brief
      review presents a stepwise approach to this procedure and discusses recent
      evidence related to dermatologic minor surgery.

PMID- 21962183
TI  - Techniques to minimize the pain of injected local anesthetic.
AB  - The process of injecting local anesthetic still often remains the most
      uncomfortable part of dermatologic surgery for patients. This review discusses
      strategies that may be used to reduce this discomfort.

PMID- 21962184
TI  - Toxic effects of skin-lightening products in Canadian immigrants.
AB  - BACKGROUND: The cultural practice of skin bleaching is highly prevalent in
      Africa. Most reported cases of toxic effects of skin-lightening products occur in
      this region. OBJECTIVE: To describe cases of misuse of over-the-counter (OTC)
      cosmetic skin-lightening products occurring in Canadian immigrants. METHODS: Two
      cases of Canadian immigrants with severe complications from OTC skin-bleaching
      agents were identified in a community-based dermatology practice in Toronto. The
      case histories were reviewed and analyzed. RESULTS: A 28-year-old African
      Canadian woman developed extensive striae from long-term use of a topical cream
      containing clobetasol that she had purchased in a Caribbean health food store. A
      55-year-old African-Canadian woman developed exogenous ochronosis from the use of
      a topical bleaching agent she had purchased in Ghana. CONCLUSION: Cosmetic skin
      lightening with unregulated topical products occurs in Canada. Dermatologists
      working in Canada need to be aware of this practice to provide appropriate
      directive care.

PMID- 21962185
TI  - Two-stage reconstruction of head and neck defects after tumor resection with a
      dermal regeneration template.
AB  - BACKGROUND: Large defects after tumor resection in the head and neck area can be
      reconstructed with local flaps or skin grafts or heal by secondary intention.
      Especially in elderly patients, a rapid procedure with an acceptable aesthetic
      and reliable functional outcome is required. OBJECTIVE: We investigated an
      alternative strategy using the Integra Dermal Regeneration Template (IDRT) for
      the reconstruction of large defects. METHODS: In 18 patients (75 +/- 3 years), 19
      extended head and neck defects were treated with IDRT to enhance healing.
      RESULTS: The mean defect size was 32 +/- 7 cm2. The defects were transplanted
      within a mean postoperative time of 25 +/- 2 days and overall showed good
      cosmetic results and stable scars. The mean follow-up time was 11 +/- 1 months.
      Minor complications were hyperpigmentation (n  =  1), small ulcus (n  =  1), one
      minor ectropion (n  =  1), and partial loss of the skin graft after immediate
      radiotherapy (n  =  1). In one patient, the silicon layer had to be removed after
      8 days owing to partial destruction of the IDRT. We observed shrinkage of 50 +/-
      4% within 6 months. CONCLUSION: IDRT is an alternative technique for the
      reconstruction of extended head and neck defects. It can be conducted without
      major complications and with a short healing time and acceptable cosmetic results
      in elderly patients.

PMID- 21962186
TI  - Likelihood of dermatology patients to inquire about sun protection measures
      during a regular clinic visit.
AB  - BACKGROUND: Health information-seeking behavior refers to ways individuals
      acquire health information. Few studies demonstrate its association with skin
      cancer. OBJECTIVES: To determine the likelihood of patients to inquire about sun
      protection methods from dermatologists and whether such knowledge will affect
      their preventive behaviors. METHODS: Over a 2-month period, 396 dermatology
      patients completed a survey assessing their sun awareness knowledge and inquiry
      about sun protection measures. Features associated with increased skin cancer
      risk were correlated with patients' inquiry about sun protection information and
      their future intentions to practice safe sun behavior. RESULTS: One in seven
      patients (13.8%) inquired about sun protection measures. Patients with features
      known to be associated with increased skin cancer risk infrequently inquired
      about sun protection methods (4.5-23.8%). Post-physician counseling, patients
      with previous sun awareness education had a greater intention to use sunscreen
      routinely (41.4% vs 28.3%, p  =  .01), avoid the sun (31.2% vs 18.2%, p  = 
      .004), and wear sun-protective clothing (32.5% vs 23.2%., p  =  .05). CONCLUSION:
      Patients' desire for medical information from physicians does not translate
      efficiently into seeking sun awareness information from dermatologists.
      Dermatologists should play a greater proactive role in skin cancer prevention
      through initiation of regular personalized discussions on sun awareness issues.

PMID- 21962187
TI  - Methotrexate-induced cutaneous ulcers in a nonpsoriatic patient: case report and
      review of the literature.
AB  - BACKGROUND: Methotrexate is a mainstay of treatment for autoimmune conditions
      such as rheumatoid arthritis and psoriasis. Methotrexate has numerous potential
      side effects and, in rare circumstances, can lead to cutaneous ulceration.
      Methotrexate can cause skin ulceration, and stopping this medication can lead to
      complete healing of the ulcerated lesion. OBSERVATIONS: A 67-year-old man with
      rheumatoid arthritis on long-term methotrexate therapy presented to hospital with
      ulcers on his hands, elbows, and lower extremities. He had no history of
      psoriasis. Shortly after admission, the patient was noted to have pancytopenia. A
      bone marrow biopsy showed a hypocellular marrow. Both the cutaneous ulcers and
      the hypocellular marrow were thought to be induced by methotrexate. The ulcerated
      areas were biopsied, and histopathology showed no evidence of vasculitis. After 1
      month of rehabilitative skin care, the patient's ulcers healed almost completely
      and his bone marrow suppression recovered. CONCLUSION: We report the fifth case
      of methotrexate-induced cutaneous ulceration in a nonpsoriatic patient and review
      the literature on this unusual drug reaction. Methotrexate can induce cutaneous
      ulceration in nonpsoriatic patients and should be considered a potential cause of
      ulceration in patients treated with this antimitotic agent.

PMID- 21962188
TI  - Worsening of vitiligo and onset of new psoriasiform dermatitis following
      treatment with infliximab.
AB  - BACKGROUND: Vitiligo is a depigmentation disorder caused by melanocyte
      destruction that possibly results from an autoimmune mechanism. Psoriasis is an
      immune-mediated, chronic, inflammatory dermatosis. Although tumor necrosis factor
      alpha antagonists (anti-TNF-alpha), such as infliximab, are effective in treating
      psoriasis, many cases reported in the literature indicate that psoriasis might
      also be induced by treatment with infliximab. Some studies also suggest that TNF
      alpha antagonists might be an effective treatment for vitiligo because the
      disorder is characterized by increased levels of TNF-alpha, indicating that it
      might play a role in the pathogenesis of this disease. OBJECTIVE: We report a
      case of psoriasiform dermatitis with vacuolar interface reaction that occurred
      after infliximab therapy in a patient with vitiligo. METHOD: A 17-year-old male
      patient with vitiligo vulgaris was treated with an intravenous infusion of 5
      mg/kg of infliximab at 0, 2, and 6 weeks and then once every 6 weeks over a span
      of 6 months. The patient was monitored both clinically and with laboratory
      investigations. He had no personal or family history of psoriasis. He tolerated
      the treatment well, without side effects. However, he developed a biopsy-proven
      psoriasiform lesion for the first time 4 months after he completed his sixth dose
      of infliximab. His vitiligo also worsened. CONCLUSION: This case report shows
      that infliximab given for vitiligo did not improve the disorder and that the
      vitiligo actually progressed. Moreover, psoriasiform lesions developed after this
      therapy. Further studies are needed to identify the effects of infliximab in
      patients with vitiligo.

PMID- 21962189
TI  - A challenging case of multiply recurrent nasal basal cell carcinoma.
AB  - BACKGROUND: Basal cell carcinoma (BCC) is the most common human malignancy
      worldwide and represents a significant cost to health care systems. Most cases
      occur on the head and neck, and many are successfully treated with relatively
      simple measures. However, if high-risk or complicated cases are not treated
      effectively, they may result in considerable disfigurement or morbidity. We
      report on a patient with a complex nasal basal cell carcinoma (BCC) that failed
      multiple treatments by electrodesiccation and curettage (EDC). Management
      strategies for primary and recurrent BCC, including EDC, standard excision, Mohs
      micrographic surgery (MMS), and radiation therapy, are discussed. This case
      required extensive resection, and we review the literature for predictive factors
      of significant subclinical spread. OBJECTIVE: To present a complex case that
      illustrates the management options of high-risk, recurrent BCC of the head and
      neck. MATERIALS AND METHODS: Case report and review of the literature. RESULTS:
      MMS offers the lowest recurrence rate in the treatment of recurrent BCC in
      surgical candidates. A validated risk scale may predict subclinical spread in
      patients with BCC of the head and neck. CONCLUSIONS: BCC can progress to locally
      advanced disease, necessitating definitive treatment. EDC performed by an
      experienced dermatologist may offer cure rates comparable to those of surgery in
      lower-risk BCC. However, in higher-risk tumors, such as recurrent or larger
      lesions, methods that ensure clear margins should be considered first line,
      especially in sensitive locations. The routine use of a validated risk scale can
      better prepare patients and dermatologists for potentially extensive resections.
      In cases with risk of extensive involvement, strategies to clearly communicate
      options and progress at all stages of the process should be available.

PMID- 21962190
TI  - Unusual case of proximal calciphylaxis without renal failure.
AB  - BACKGROUND: Calciphylaxis is a rare syndrome of vascular calcification with
      subsequent cutaneous and tissue necrosis. It usually manifests as a complication
      of end-stage renal failure, affecting 1 to 4% of long-term dialysis patients.
      Very exceptionally, it can occur without chronic renal failure. OBJECTIVE: The
      goal of this study was to discuss an exceptional case of extensive calciphylaxis
      in the absence of chronic renal failure and its successful management. METHODS:
      We present a case of a 31-year-old woman with extensive proximal, ulcerated
      calciphylaxis without associated chronic renal failure. Our patient had quite a
      few risk factors associated with the pathogenesis of calciphylaxis, such as
      obesity, malnutrition, and a transient episode of acute renal failure. RESULTS:
      She was successfully treated with sodium thiosulfate, extensive wound debridement
      (more than 30% total body surface), and subsequent skin grafts. The patient has
      miraculously survived this often fatal condition. CONCLUSION: Calciphylaxis can
      occur even in the absence of chronic renal failure. This often fatal condition
      can be managed successfully with a combination of aggressive wound control and
      the fairly newly described sodium thiosulfate therapy.

PMID- 21962192
TI  - Inner canthus hypertrichosis: a side effect of prostaglandin analogue treatment
      for glaucoma.

PMID- 21962191
TI  - Annular elastolytic giant cell granuloma associated with temporal arteritis
      leading to blindness.
AB  - BACKGROUND: Annular elastolytic giant cell granuloma (AEGCG) is a rare
      granulomatous disorder characterized by giant cells in the dermis phagocytosing
      damaged elastin fragments. OBJECTIVE: We report a case of a 71-year-old man
      presenting with erythematous plaques in predominantly sun-exposed areas. METHOD:
      A diagnosis of AEGCG was made based on the clinical and histologic picture, and
      treatment with systemic steroids was initiated. However, while tapering the
      steroid dose, the patient developed a radiating headache that progressed to
      temporal arteritis and eventual blindness in the right eye. CONCLUSION: There
      have been only two previous case reports presenting an association between AEGCG
      and temporal arteritis. This report explores AEGCG and its possible relationship
      to temporal arteritis along with possible treatment regimens cited in the current
      literature.

PMID- 21962193
TI  - The diversity of endeavour in homeopathy.

PMID- 21962194
TI  - Short-term effects of repeated olfactory administration of homeopathic sulphur or
      pulsatilla on electroencephalographic alpha power in healthy young adults.
AB  - INTRODUCTION: Homeopathic pathogenetic trials usually rely on symptom self report
      measures. Adding objective biomarkers could enhance detection of subtle initial
      remedy effects. The present feasibility study examined electroencephalographic
      (EEG) effects of repeated olfactory administration of two polycrest remedies.
      METHODS: College student volunteers (ages 18-30, both sexes) from an introductory
      psychology course were screened for good health and relatively elevated Sulphur
      or Pulsatilla symptom scores on the Homeopathic Constitutional Type Questionnaire
      (CTQ). Subjects underwent a series of 3 once-weekly double-blind sessions during
      which they repeatedly sniffed the remedy matched to their CTQ type and solvent
      controls. Each remedy was given in a 6c, 12c, and 30c potency, one potency per
      week, in randomly assigned order. Solvent controls included both plain distilled
      water and a water-ethanol (95%) solution. All sniff test solutions were further
      diluted just prior to laboratory sessions (0.5 ml test solution in 150 ml
      distilled water). Within a session, remedies and control solvents were
      administered via 2-s sniffs (8 sniffs of each of 4 different succussion levels
      for the potency in randomized order). Primary outcome variable was relative EEG
      power (alpha 1 8-10 Hz; alpha 2 10-12 Hz) averaged over 19 electrode sites,
      including all succussions for a given potency. RESULTS: Mixed-effect models
      revealed significant main effects for remedy type (Sulphur >Pulsatilla) in both
      alpha bands, controlling for gender, baseline resting EEG alpha, and solvent
      control responses. Additional analyses showed significant nonlinear interactions
      between dilution and time (weekly session) in alpha 2 for both remedies and alpha
      1 for Sulphur. CONCLUSION: EEG alpha offers an objective biomarker of remedy
      effects for future studies and potential method for distinguishing time-dependent
      effects of specific remedies and remedy potencies from one another.

PMID- 21962195
TI  - Measuring the effectiveness of homeopathic care through objective and shared
      indicators.
AB  - OBJECTIVE: To test a methodology to evaluate, at population level, the
      effectiveness of homeopathic treatment through standard objective public health
      indicators. METHODS AND SETTINGS: Indicators of hospitalization and drug use were
      obtained from the Health Statistical Documentation System of Tuscany for two
      homeopathic centers in the Local Health Authority of Pisa, Italy. We compared
      homeopathic users with the general population in the same area and by comparing
      patients before and after homeopathic treatment. RESULTS: The homeopathic
      patients used less drugs than the reference population, this effect was more
      evident for patients with repeated homeopathic consultations. A significant
      decrease in drug use was found on comparing the same patients before and after
      homeopathic treatment. Hospitalization indicators tended to favour patients who
      had received homeopathic treatment but were not always statistically significant.
      CONCLUSIONS: This paper demonstrates a new methodological approach to assess the
      effectiveness of a therapeutic modality, without ad-hoc clinical trials. This
      methodology can be used by public health institutions in which non-conventional
      medicines are integrated into the public health care system.

PMID- 21962196
TI  - Ultra high dilution of triiodothyronine modifies cellular apoptosis in Rana
      catesbeiana tadpole tail in vitro.
AB  - BACKGROUND: Ultra High Dilutions (UHD) are diluted beyond the Avogadro limit with
      dynamization (dilution with succussion). The process of anuran amphibian
      metamorphosis is controlled by thyroid hormones, including the resorption of the
      tadpole tail. METHODS: A randomized and blinded study was performed to
      investigate the influence of triiodothyronine (T3) 5.10(-24)M (10cH) on apoptosis
      induced by T3 100 nM in Rana catesbeiana tadpoles' tail tips, in vitro. Explants
      were randomized to three groups: control: no T3 in pharmacological or UHD dose;
      test: T3 100 nM and challenged with T3 10cH (UHD); positive control: T3 100 nM,
      treated with unsuccussed ethanol. The apoptotic index and the area of explants of
      test and control groups at the first and final day of the experiment were
      compared by t-test. RESULTS: There was no difference in tail tip area between
      test and control groups, but a significantly higher (p<0.01) index of apoptosis
      in explants of the test group. CONCLUSION: This data suggest that T3 10cH
      modifies the effect of T3 at pharmacological dose, opening new perspectives for
      further studies and investigation of the dose-effect curve.

PMID- 21962197
TI  - Mercurius solubilis: actions on macrophages.
AB  - BACKGROUND: Macrophages play central roles in homeostasis as well as host defence
      in innate and acquired immunity, auto-immunity and immunopathology. Our research
      group has demonstrated the effects of highly diluted toxic substances in
      macrophages. AIM: To investigate if highly diluted Mercurius solubilis (Merc
      sol), can activate or modulate macrophage functions. METHODS: We evaluated the
      effects of Merc sol in the 6, 12, 30 and 200 centesimal high dilutions (CH)
      potencies on mice peritoneal macrophages (in vitro and in vivo). Merc sol was
      added to mice's drinking water for 7 days (in vivo treatment) and animals were
      euthanised and cells were collected. In vitro treatment was performed on
      macrophages and bone-marrow cell cultures. RESULTS: Macrophages showed activated
      morphology, both when Merc sol was added directly to the cell culture and to
      drinking water. The in vitro experiments showed enhanced morphological
      activation, increased interferon (IFN)gamma release in the supernatant at lower
      dilutions and interleukin (IL)-4 production at higher dilutions. Increase in
      nitric oxide and decrease in superoxide (O(2)(-)) and hydrogen peroxide
      (H(2)O(2)) were also observed. In vivo treatment caused a decrease in O(2)(-) and
      increase in H(2)O(2) production by macrophages. DISCUSSION: Taken together, the
      results allow us to conclude that highly diluted Merc sol modulates reactive
      oxygen species (ROS), reactive nitrogen species (RNS) and cytokine secretion,
      which are central mediators of the immune system, wound healing and body
      homeostasis.

PMID- 21962198
TI  - Different forms of administration of biotherapy 7dH in mice experimentally
      infected by Trypanosoma cruzi produce different effects.
AB  - OBJECTIVE: To evaluate the effects of different forms of administration of the
      blood trypomastigotes biotherapy 7dH in mice experimentally infected with
      Trypanosoma cruzi. MATERIAL AND METHODS: Male swiss mice were inoculated with
      1400 blood trypomastigotes of the Y strain of T. cruzi and allocated into 5
      treatment groups: IC (distilled water); TCBZ (benznidazole); TBA(7dH) (biotherapy
      7dH 20 days after infection); TBB(7dH)7 (biotherapy 7dH seven days before
      infection); TBB(7dH)30 (biotherapy 7dH 30 days before infection). Parasitological
      parameters assessed included pre-patent and patent periods, parasitemia peak,
      total parasitemia, mortality and survival rates. Cure index was obtained by fresh
      blood examination, hemoculture and polymerase chain reaction (PCR). RESULTS: The
      TBB(7dH)7 group showed a reduction in parasitemia peak, parasitemia area under
      the curve and total parasitemia. TBB(7dH)30 showed a tendency to increased pre
      patent and survival periods, peak parasitemia was increased without increased
      total parasitemia. TBA(7dH) did not present significant alterations in the
      parasitological parameters analyzed. CONCLUSIONS: Biotherapy 7dH given before
      infection (7 or 30 days) produces different effects suggesting modulation of the
      host's immune system. The effects range from reduced parasitemia to its effective
      increase. The use of biotherapy to treat T. cruzi infection including dose,
      potency and schedule deserves further investigation.

PMID- 21962199
TI  - New homeopathic medicines: use of modern drugs according to the principle of
      similitude.
AB  - BACKGROUND: The homeopathic method is based on the application of the principle
      of therapeutic similitude (similia similibus curentur), using medicines that
      cause effects similar to the symptoms of disease in order to stimulate the
      reaction of the organism against disturbances. Such vital, homeostatic or
      paradoxical reaction of the organism can be scientifically explained on the basis
      of the rebound effect of modern drugs. AIMS: This article presents the conclusion
      of a study aiming at a method to use modern drugs with homeopathic criteria.
      METHODS: Adverse effects as catalogued in United States Pharmacopoeia Dispensing
      Information Drug monographs were collected. RESULTS: A homeopathic materia medica
      and repertory comprising 1251 modern drugs to be employed according to the
      principle of therapeutic similitude was developed. CONCLUSION: Besides supplying
      a basis for homeopathy as a medical rationale related to scientific pharmacology,
      this study makes available a method that may broaden the scope of intervention of
      homeopathy in present day diseases.

PMID- 21962200
TI  - Undergraduate homeopathy education in Europe and the influence of accreditation.
AB  - CONTEXT: The safety of patients consulting with practitioners of complementary
      and alternative medicine (CAM) partially depends on practitioners' competence,
      and thus the standard of undergraduate education. OBJECTIVES: Describe
      undergraduate homeopathy courses in Europe, student/graduate numbers and whether
      there were differences between recognised/accredited and non-recognised/non
      accredited courses. METHODS: Cross sectional survey of current homeopathy
      undergraduate education in Europe in 2008. Data from 145 (94.8%) out of 153
      identified courses were collected. Eighty-five (55.6%) responded to a
      questionnaire survey. For others some data was extracted from their websites.
      Only data from the questionnaire survey is used for the main analysis. FINDINGS:
      The average course in the questionnaire survey had 47 enrolled students and 142
      graduates, and lasted 3.6 years part-time. An estimated 6500 students were
      enrolled and 21,000 had graduated from 153 identified European undergraduate
      homeopathy courses. Out of 85 courses most had entry requirements and provided
      medical education (N = 48) or required students to obtain this competence
      elsewhere (N = 33). The average number of teaching hours were 992 (95% confidence
      interval (CI) 814, 1170) overall, with 555 h (95%CI 496, 615) for homeopathy.
      Four out of five courses were recognised/accredited. Recognised/accredited part
      time courses lasted significantly longer than non-recognised/non-accredited
      courses (difference 0.6 years, 95%CI 0.0-1.2, P = 0.040), and offered
      significantly larger numbers of teaching hours in homeopathy (difference 167 h,
      95%CI 7-327, P = 0.041). CONCLUSIONS: About 6500 currently enrolled students are
      doing undergraduate homeopathy education in Europe and 21,000 have graduated from
      such courses over a period of about 30 years. Undergraduate homeopathy education
      in Europe is heterogeneous. Recognised/accredited courses are more extensive with
      more teaching hours.

PMID- 21962201
TI  - Quasi-quantum model of potentization.
AB  - Analytical time-dependent functions describing the change of the concentration of
      the solvent S(t) and the homeopathic active substance A(t) during decimal and
      centesimal dilution are derived. The function S(t) is a special case of the West
      Brown-Enquist curve describing ontogenic growth, the increase in concentration of
      the solvent during potentization resembles the growth of biological systems. It
      is demonstrated that the macroscopic S(t) function is the ground state solution
      of the microscopic non-local Horodecki-Feinberg equation for the time-dependent
      Hulthen potential at the critical screening. In consequence potentization belongs
      to the class of quasi-quantum phenomena playing an important role both in
      biological systems and homeopathy. A comparison of the results predicted by the
      model proposed with the results of experiments on delayed luminescence of a
      homeopathic medicine is made.

PMID- 21962202
TI  - Epidermolysis bullosa: report of three cases treated with homeopathy.
AB  - Epidermolysis bullosa (EB) is a group of rare genetic disorders characterized by
      recurrent blistering as a result of even minor traction of epithelial lined
      tissues, most remarkably the skin. Associated morbidity is serious for all
      patients affected due to the presence of large areas of denudated skin thus
      susceptible to infection. There is currently no available treatment in
      conventional medicine. This article reports the case of 3 children successfully
      treated with individualized homeopathic medicines.

PMID- 21962203
TI  - Homeopathic and integrative treatment for feline hyperthyroidism--four cases
      (2006-2010).
AB  - Hyperthyroidism is a frequent veterinary problem, particularly in elderly cats.
      Homeopathic treatment and other integrative modalities were provided for four
      hyperthyroid cats whose owners did not want conventional treatment. Symptomatic
      homeopathic treatment with Thyroidinum was helpful in one cat. All cats were
      prescribed an appropriate individualized homeopathic remedy. All four cats showed
      resolution of clinical signs; three attained normal thyroid hormone levels. Three
      cats later received acupuncture and/or herbal medicines; two cats later received
      symptomatic homeopathic remedies. Two cats are thriving after over 3.5 and 4.25
      years of treatment; two were euthanized for unrelated problems after 3 and 4
      years of treatment. Homeopathic and complementary therapies avoid the potential
      side effects of methimazole and surgical thyroidectomy, they are less costly than
      radioactive iodine treatment, and they provide an option for clients who decline
      conventional therapies.

PMID- 21962204
TI  - Use of homeopathic preparations in experimental studies with abiotically stressed
      plants.
AB  - BACKGROUND: Experimental research on the effects of homeopathic treatments on
      impaired plants was last reviewed in 1990. OBJECTIVES: To compile a systematic
      review of the existing literature on basic research in homeopathy with
      abiotically stressed plants using predefined criteria. METHODS: The literature
      search was carried out on publications that reported experiments on homeopathy
      using abiotically stressed whole plants, seeds, plant parts and cells from 1920
      to 2010. Outcomes had to be measured by established procedures and statistically
      evaluated. Using of a Manuscript Information Score (MIS) we identified those
      publications that provided sufficient information for proper interpretation
      (MIS>=5). A further evaluation was based on the use of adequate controls to
      investigate specific effects of homeopathic preparations and on the use of
      systematic negative control experiments. RESULTS: A total of 34 publications with
      abiotically stressed plants was identified, published between 1965 and 2010. The
      34 publications described a total of 37 experimental studies. Twenty-two studies
      included statistics, 13 had a MIS>=5, 8 were identified with adequate controls
      and 4 with negative control experiments. Significant and reproducible effects
      with decimal and centesimal potencies were found, including dilution levels
      beyond Avogadro's number. One experimental model was independently assessed by
      another research team and yielded inverted results compared to the original
      trial. CONCLUSIONS: Abiotically stressed plant models seem to be a useful
      approach to investigate homeopathic basic research questions, but more
      experimentation and especially more independent replication trials are needed.
      Systematic negative control experiments should be implemented on a routine basis
      to exclude false-positive results.

PMID- 21962205
TI  - Review of the use of high potencies in basic research on homeopathy.
AB  - The HomBRex database includes details of about 1500 basic research experiments in
      homeopathy. A general overview on the experiments listed in the HomBRex database
      is presented, focusing on high dilutions and the different settings in which
      those were used. Though often criticised, many experiments with remedies diluted
      beyond Avogadro's number demonstrate specific effects. A total of 830 experiments
      employing high potencies was found; in 745 experiments of these (90%), at least
      one positive result was reported. Animals represent the most often used model
      system (n=371), followed by plants (n=201), human material (n=92), bacteria and
      viruses (n=37) and fungi (n=32). Arsenicum album (Ars.) is the substance most
      often applied (n=101), followed by Sulphur (Sulph.) and Thuja (Thuj.) (n=65 and
      48, respectively). Proving, prophylactic and therapeutic study designs have all
      been used and appear appropriate for homeopathy basic research using high
      dilutions. The basic research data set to support specific effects unique to high
      dilutions and opposite to those observed with low dilutions is, to date,
      insufficient.

PMID- 21962206
TI  - No fear of ghosts in Lycopodium: a contribution to the discussion on repertory
      reliability.
AB  - BACKGROUND: Repertory mistakes in modern homeopathy have been pointed out since
      the early years after the publication of the sixth edition of Kent's repertory. A
      structural error of many current repertories is the use of Kent's repertory as a
      basic information source. 'Fear of ghosts' is widely considered to be a symptom
      of Lycopodium clavatum by the homeopathic community. OBJECTIVES: To demonstrate
      that the source of 'fear of ghosts' in Lycopodium clavatum was an inaccurate
      translation, that has been spread by secondary sources and to review Hahnemann's
      conception and efforts towards a reliable repertory. RESULTS: The symptom 'fear
      of ghosts' does not exist in the primary source, being the product of a
      misunderstanding of the English translation of Hahnemann's original record, 'fear
      of frightful imaginary images'. Hahnemann's efforts to compile a reliable and
      complete dictionary of Materia Medica were also briefly presented, as well as
      Ruckert's repertory, which, in addition to collating and classifying symptoms in
      alphabetical rubrics and sub-rubrics, displayed them completely, as registered in
      primary sources. CONCLUSION: The misunderstanding about 'fear of ghosts' in
      Lycopodium clavatum exemplifies how distant current homeopathic information is
      from its primary sources and from Hahnemann's ideal of a symptom-lexicon. In
      spite of its technical limitations, Ruckert's repertory, which was strongly
      recommended by Hahnemann, can be considered as a template for new repertories
      based on primary sources.

PMID- 21962207
TI  - Clinical trial of homeopathy in rheumatoid arthritis.

PMID- 21962208
TI  - Antiophidic solanidane steroidal alkaloids from Solanum campaniforme.
AB  - Three new solanidane alkaloids bearing a 22,23-epoxy ring (1-3) and four known
      compounds were isolated from leaves of Solanum campaniforme. The structures were
      determined using spectroscopic techniques, including 1D and 2D NMR, and HRESIMS
      experiments. The antiophidic activity of the alkaloids was tested against
      Bothrops pauloensis venom. Compounds 1-3 completely inhibited myotoxicity without
      inhibiting phospholipase A2 activity of the venom, while hemorrhage and skin
      necrosis were significantly reduced in the presence of alkaloids 1 and 2.

PMID- 21962209
TI  - The relationship between knee extension strength and lower extremity functions in
      nursing home residents with dementia.
AB  - PURPOSE: To assess the relationships between knee extension strengths and lower
      extremity functions in subjects with dementia and to predict lower extremity
      functions using knee extension strength. METHODS: Fifty-four nursing home
      residents with dementia were enrolled in the study. The strength of the knee
      extensor was measured using a hand-held dynamometer. To predict lower extremity
      functions, subjects were classified into two groups: those who could dress their
      lower body, toilet, transfer to bed/toilet/shower and walk independently, and
      those who required assistance. Knee extension strength was compared between the
      two groups. RESULTS: Logistic regression analysis showed that the strength of the
      knee extensor muscles was a significant predictor of the ability to dress the
      lower body (odds ratio, 109.90; 95% CI, 7.60-1589.49), toileting (odds ratio,
      18.29; 95% CI, 2.41-138.84), transferring to bed/toilet/shower (odds ratio,
      39.70; 95% CI, 4.51-349.08), and gait performance (odds ratio, 12.77; 95% CI,
      2.30-70.77). The curve of the negative and positive predictive values indicated
      that a cutoff score of 0.8 Nm/kg would provide the best balance for dressing the
      lower body and toileting; 1.2 Nm/kg for transferring to bed/toilet/shower; and
      0.6 Nm/kg for gait performance. CONCLUSIONS: Knee extension strength was
      significantly related to the lower extremity functions in people with dementia.
      Moreover, threshold levels of strength existed that could predict lower extremity
      dysfunctions in people with dementia.

PMID- 21962210
TI  - Trauma center accessibility for road traffic injuries in Hanoi, Vietnam.
AB  - BACKGROUND: Rapid economic growth in Vietnam over the last decade has led to an
      increased frequency of road traffic injury (RTI), which now represents one of the
      leading causes of death in the nation. Various efforts toward injury prevention
      have not produced a significant decline in the incidence of RTIs. Our study
      sought to describe the geographic distribution of RTIs in Hanoi, Vietnam and to
      evaluate the accessibility of trauma centers to those injured in the city.
      METHODS: We performed a cross-sectional study using Hanoi city police reports
      from 2006 to describe the epidemiology of RTIs occurring in Hanoi city.
      Additionally, we identified geographic patterns and determined the direct
      distance from injury sites to trauma centers by applying geographical information
      system (GIS) software. Factors associated with the accessibility of trauma
      centers were evaluated by multivariate regression analysis. RESULTS: We mapped
      1,271 RTIs in Hanoi city. About 40% of RTIs occurred among people 20-29 years of
      age. Additionally, 63% of RTIs were motorcycle-associated incidents. Two peak
      times of injury occurrence were observed: 12 am-4 pm and 8 pm-0 am. "Hot spots"
      of road traffic injuries/fatalities were identified in the city area and on main
      highways using Kernel density estimation. Interestingly, RTIs occurring along the
      two north-south main roads were not within easy access of trauma centers.
      Further, fatal cases, gender and injury mechanism were significantly associated
      with the distance between injury location and trauma centers. CONCLUSIONS:
      Geographical patterns of RTIs in Hanoi city differed by gender, time, and injury
      mechanism; such information may be useful for injury prevention. Specifically,
      RTIs occurring along the two north-south main roads have lower accessibility to
      trauma centers, thus an emergency medical service system should be established.

PMID- 21962211
TI  - Elevated placenta growth factor predicts pneumonia in patients with chronic
      obstructive pulmonary disease under inhaled corticosteroids therapy.
AB  - BACKGROUND: An increased incidence of pneumonia in patients with chronic
      obstructive pulmonary disease (COPD) under inhaled corticosteroid (ICS) therapy
      was noticed in previous studies. We performed a prospective study to elucidate
      the risk factors for the development of pneumonia in this group of patients.
      METHODS: A prospective, non-randomized study with patients diagnosed as having
      COPD from 2007 to 2008 identified in the Far Eastern Memorial Hospital were
      recruited. We recorded data for all patients, including clinical features and
      signs, demographic data, lung function status, and medications. Bio-markers such
      as C-reactive protein (CRP) and placenta growth factor (PlGF) were checked at
      first diagnosis. Every acute exacerbation was also recorded, especially pneumonia
      events, which were confirmed by chest radiography. Multivariate analysis was
      performed with stepwise logistic regression for pneumonia risk factors. RESULTS:
      274 patients were diagnosed as having COPD during the study period and 29
      patients suffered from pneumonia with a prevalence of 10.6%. The rate was
      significantly higher in patients with ICS therapy (20/125, 16%) compared with
      those without ICS (9/149, 6%) (p = 0.02). We stratified ICS therapy into medium
      dose (500-999 ug/day fluticasone equivalent, 71 patients) and high dose (1000
      ug/day and higher fluticasone equivalent, 54 patients) group. There was no
      statistical difference in the incidence of pneumonia between these two group
      (medium dose: 13/71, 18.3% vs. high dose: 7/54, 12.9%, p = 0.47). Multivariate
      analysis was performed to identify the risk factors for developing pneumonia and
      included forced expiratory volume in one second (FEV1) less than 40% of predicted
      (odds ratio (OR) 2.2, 95% confidence interval (CI): 1.1-6.9), ICS prescription
      ((OR) 2.4, 95% (CI): 1.3-8.7), the presence of diabetes mellitus (DM) (OR 2.6,
      95% CI: 1.2-9.4) and PlGF level over 40 pg/L (OR 4.1, 95% CI: 1.5-9.9).
      CONCLUSION: ICS therapy in patients with COPD increased the risk of pneumonia.
      However, there was no relationship between the incidence of pneumonia and dosage
      of ICS. Additionally, advanced COPD status, DM and elevated PlGF level were
      independent risk factors for the development of pneumonia. PlGF would be a good
      novel biomarker for predicting pneumonia.

PMID- 21962212
TI  - Adsorption behavior of hydrophobically modified polyelectrolytes onto amino- or
      methyl-terminated surfaces.
AB  - The adsorption of hydrophobically modified polyelectrolytes derived from
      poly(maleic anhydride-alt-styrene) (P(MA-alt-St)) containing in their side chain
      aryl-alkyl groups onto amino- or methyl-terminated silicon wafers was
      investigated. The effect of the spacer group, the chemical nature of the side
      chain, molecular weight of polyelectrolyte, and ionic strength of solution on the
      polyelectrolyte adsorbed amount was studied by null ellipsometry. The adsorbed
      amount of polyelectrolyte increased with increasing ionic strength, in agreement
      with the screening-enhanced adsorption regime, indicating that hydrophobic
      interactions with the surface play an important role in the adsorption process.
      At constant ionic strength, the adsorbed amount was slightly higher for
      polyelectrolytes with larger alkyl side chain and decreased with the
      hydrophobicity of aryl group. The adsorption behavior is discussed in terms of
      the side chain flexibility of the polymer. Characteristics of the adsorbed layer
      were studied by atomic force microscopy (AFM) and contact angle measurements. AFM
      images show the presence of aggregates and closed globular structure of
      polyelectrolyte onto the amino- or methyl-terminated surface, which agrees with a
      3D and 2D growth mechanism, respectively. Fluorescence measurements showed that
      the aggregation of polyelectrolyte containing the hydrophobic naphthyl group
      occurs already in the solution. However, the aggregation of polyelectrolytes
      containing the phenyl group in its side chain is not observed in solution but is
      induced by the amino-terminated surface. This difference can be explained in
      terms of the higher flexibility of side chain bearing the phenyl group. The
      polyelectrolyte films showed a high chemical heterogeneity and moderate
      hydrophobicity.

PMID- 21962213
TI  - Quantitation of benzo[a]pyrene metabolic profiles in human bronchoalveolar (H358)
      cells by stable isotope dilution liquid chromatography-atmospheric pressure
      chemical ionization mass spectrometry.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants
      and are carcinogenic in multiple organs and species. Benzo[a]pyrene (B[a]P) is a
      representative PAH and has been studied extensively for its carcinogenicity and
      toxicity. B[a]P itself is chemically inert and requires metabolic activation to
      exhibit its toxicity and carcinogenicity. Three major metabolic pathways have
      been well documented. The signature metabolites generated from the radical cation
      (peroxidase or monooxygenase mediated) pathway are B[a]P-1,6-dione and B[a]P-3,6
      dione, the signature metabolite generated from the diol-epoxide (P450 mediated)
      pathway is B[a]P-r-7,t-8,t-9,c-10-tetrahydrotetrol (B[a]P-tetrol-1), and the
      signature metabolite generated from the o-quinone (aldo-keto reductase mediated)
      pathway is B[a]P-7,8-dione. The contributions of these different metabolic
      pathways to cancer initiation and the exploitation of this information for cancer
      prevention are still under debate. With the availability of a library of
      [(13)C(4)]-labeled B[a]P metabolite internal standards, we developed a sensitive
      stable isotope dilution atmospheric pressure chemical ionization tandem mass
      spectrometry method to address this issue by quantitating B[a]P metabolites from
      each metabolic pathway in human lung cells. This analytical method represents a
      500-fold increased sensitivity compared with that of a method using HPLC
      radiometric detection. The limit of quantitation (LOQ) was determined to be 6
      fmol on column for 3-hydroxybenzo[a]pyrene (3-OH-B[a]P), the generally accepted
      biomarker for B[a]P exposure. This high level of sensitivity and robustness of
      the method was demonstrated in a study of B[a]P metabolic profiles in human
      bronchoalveolar H358 cells induced or uninduced with the AhR ligand, 2,3,7,8
      tetrachlorodibenzodioxin (TCDD). All the signature metabolites were detected and
      successfully quantitated. Our results suggest that all three metabolic pathways
      contribute equally in the overall metabolism of B[a]P in H358 cells with or
      without TCDD induction. The sensitivity of the method should permit the
      identification of cell-type differences in B[a]P activation and detoxication and
      could also be used for biomonitoring human exposure to PAH.

PMID- 21962215
TI  - Acyl chain differences in phosphatidylethanolamine determine domain formation and
      LacY distribution in biomimetic model membranes.
AB  - Phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) are the two main
      components of the inner membrane of Escherichia coli. It is well-known that inner
      membrane contains phospholipids with a nearly constant polar headgroup
      composition. However, bacteria can regulate the degree of unsaturation of the
      acyl chains in order to adapt to different external stimuli. Studies on model
      membranes of mixtures of PE and PG, mimicking the proportions found in E. coli,
      can provide essential information on the phospholipid organization in biological
      membranes and may help in the understanding of membrane proteins activity, such
      as lactose permease (LacY) of E. coli. In this work we have studied how different
      phosphatidylethanolamines differing in acyl chain saturation influence the
      formation of laterally segregated domains. Three different phospholipid systems
      were studied: DOPE:POPG, POPE:POPG, and DPPE:POPG at molar ratios of 3:1. Lipid
      mixtures were analyzed at 24 and 37  degrees C through three different model
      membranes: monolayers, liposomes, and supported lipid bilayers (SLBs). Data from
      three different techniques, Langmuir isotherms, Laurdan generalized polarization,
      and atomic force microscopy (AFM), evidenced that only the DPPE:POPG system
      exhibited coexistence between gel (L(beta)) and fluid (L(alpha)) phases at both
      24 and 37  degrees C . In the POPE:POPG system the L(beta)/L(alpha) coexistence
      appears at 27  degrees C. Therefore, in order to investigate the distribution of
      LacY among phospholipid phases, we have used AFM to explore the distribution of
      LacY in SLBs of the three phospholipid systems at 27  degrees C, where the
      DOPE:POPG is in L(alpha) phase and POPE:POPG and DPPE:POPG exhibit
      L(beta)/L(alpha) coexistence. The results demonstrate the preferential insertion
      of LacY in fluid phase.

PMID- 21962220
TI  - Haemodialysis in an emerging centre in a developing country: a two year review
      and predictors of mortality.
AB  - BACKGROUND: Haemodialysis is the most common form of renal replacement therapy in
      Nigeria. The high cost of haemodialysis has made optimal therapy of end-stage
      renal disease difficult in Nigeria. This paper is a review of data collected over
      two years of provision of dialysis services in a new tertiary hospital in
      Southern Nigeria. METHODS: This retrospective analysis is done on data obtained
      from the patient case files and dialysis records in the first two years of
      provision of dialysis services in our centre. A gender comparison of the
      patients' baseline sociodemographic, clinical and biochemical was performed and a
      logistic regression model used to assess the predictors of mortality. RESULTS: A
      total of 98 patients had 471 sessions in the two years under review. Males and
      females had similar characteristics at baseline except for a higher median serum
      urea in the males. The commonest causes of end-stage renal disease were chronic
      glomerulonephritis (34.5%), hypertension (32.1%) and diabetes mellitus (17.9%).
      The main predictor of mortality was under treatment with haemodialysis due to
      inability to pay for more than a few dialysis sessions. CONCLUSIONS: This study
      has highlighted the unchanging demographics of our advanced kidney failure
      patients. Efforts should be aimed at subsidizing the cost of dialysis for our
      teeming population of dialysis dependent chronic kidney disease patients.

PMID- 21962221
TI  - Spectroscopic microscopy analysis of the interior pH of individual phospholipid
      vesicles.
AB  - The use of phospholipid vesicles as reaction containers, as vehicles for
      pharmaceutical drug delivery, and as model systems for cells has prompted the
      development of new methods for analyzing the structure of vesicles and their
      contents. The pH of the interior of vesicles is of particular interest when
      analytes are encapsulated and concentrated with the use of a pH gradient. While
      the interior pH is generally measured for large populations of vesicles, we
      report the measurement of the interior pH of individual vesicles as their buffer
      contents are titrated by transfer of N-methylbutylamine (NMBA) into the vesicle
      by a pH gradient. The initially acidic buffer within the vesicles is titrated
      along with a small concentration of an encapsulated pH sensitive dye, 5,6-carboxy
      SNARF-1-dextran. Images of the indicator fluorescence from each vesicle and its
      dispersed fluorescence spectrum are recorded using epi-illumination spectral
      fluorescence microscopy. From a fit of the spectra to the respective acid and
      base forms of the fluorescent indicator, the interior pH of individual vesicles
      as a function of the concentration of the NMBA titrant in the external solution
      could be determined.

PMID- 21962222
TI  - Comparative transcriptome sequencing of germline and somatic tissues of the
      Ascaris suum gonad.
AB  - BACKGROUND: Ascaris suum (large roundworm of pigs) is a parasitic nematode that
      causes substantial losses to the meat industry. This nematode is suitable for
      biochemical studies because, unlike C. elegans, homogeneous tissue samples can be
      obtained by dissection. It has large sperm, produced in great numbers that permit
      biochemical studies of sperm motility. Widespread study of A. suum would be
      facilitated by more comprehensive genome resources and, to this end, we have
      produced a gonad transcriptome of A. suum. RESULTS: Two 454 pyrosequencing runs
      generated 572,982 and 588,651 reads for germline (TES) and somatic (VAS) tissues
      of the A. suum gonad, respectively. 86% of the high-quality (HQ) reads were
      assembled into 9,955 contigs and 69,791 HQ reads remained as singletons. 2.4
      million bp of unique sequences were obtained with a coverage that reached 16.1
      fold. 4,877 contigs and 14,339 singletons were annotated according to the C.
      elegans protein and the Kyoto Encyclopedia of Genes and Genomes (KEGG) protein
      databases. Comparison of TES and VAS transcriptomes demonstrated that genes
      participating in DNA replication, RNA transcription and ubiquitin-proteasome
      pathways are expressed at significantly higher levels in TES tissues than in VAS
      tissues. Comparison of the A. suum TES transcriptome with the C. elegans
      microarray dataset identified 165 A. suum germline-enriched genes (83% are
      spermatogenesis-enriched). Many of these genes encode serine/threonine kinases
      and phosphatases (KPs) as well as tyrosine KPs. Immunoblot analysis further
      suggested a critical role of phosphorylation in both testis development and
      spermatogenesis. A total of 2,681 A. suum genes were identified to have
      associated RNAi phenotypes in C. elegans, the majority of which display embryonic
      lethality, slow growth, larval arrest or sterility. CONCLUSIONS: Using deep
      sequencing technology, this study has produced a gonad transcriptome of A. suum.
      By comparison with C. elegans datasets, we identified sets of genes associated
      with spermatogenesis and gonad development in A. suum. The newly identified genes
      encoding KPs may help determine signaling pathways that operate during
      spermatogenesis. A large portion of A. suum gonadal genes have related RNAi
      phenotypes in C. elegans and, thus, might be RNAi targets for parasite control.

PMID- 21962223
TI  - Effects of RNA interference-mediated gene silencing of JMJD2A on human breast
      cancer cell line MDA-MB-231 in vitro.
AB  - Previous data demonstrate that JMJD2A is a cancer-associated gene and may be
      involved in human breast cancer by demethylation of H3K9me3. The aim of this
      study was to investigate depressive effects on JMJD2A by transfection with JMJD2A
      sepcific siRNA in human breast cancer cell line MDA-MB-231 and effects on cell
      proliferation, invasion and migration. JMJD2A-specific siRNA was chemically
      synthesised and transfected into human breast cancer cell line MDA-MB-231.
      Expression levels of JMJD2A were detected by quantitative real-time PCR and
      Western blot analysis. Cells proliferation was evaluated by using flow cytometric
      anlysis and MTT assay. The abilities of invasion and migration were evaluated by
      cell migration and invasion assay with Boyden chambers. The results showed that
      the transfection was successful and expression levels of JMJD2A mRNA and protein
      in siRNA group were both down-regulated. By MTT assay, the mean actual absorbance
      in siRNA group was significantly lower than that in blank control group (P <
      0.05) and negative control group (P < 0.05). In addition, the percentage of cells
      in G0/G1 phase in siRNA group was significantly more than that in blank control
      group (P < 0.05) and negative control group (P < 0.05). Furthermore, by cell
      invasion and migration assay, the decreased number of migrated cells in siRNA
      group was observed (P < 0.05). These data imply that silencing JMJD2A gene could
      result in cell cycle change and proliferation inhibition, and lead to suppress
      tumor cell invasion and migration. It provides a new perspective in understanding
      the pleiotropic functions of JMJD2A and its contribution to human breast cancer.

PMID- 21962214
TI  - Treatment of neonatal sepsis with intravenous immune globulin.
AB  - BACKGROUND: Neonatal sepsis is a major cause of death and complications despite
      antibiotic treatment. Effective adjunctive treatments are needed. Newborn infants
      are relatively deficient in endogenous immunoglobulin. Meta-analyses of trials of
      intravenous immune globulin for suspected or proven neonatal sepsis suggest a
      reduced rate of death from any cause, but the trials have been small and have
      varied in quality. METHODS: At 113 hospitals in nine countries, we enrolled 3493
      infants receiving antibiotics for suspected or proven serious infection and
      randomly assigned them to receive two infusions of either polyvalent IgG immune
      globulin (at a dose of 500 mg per kilogram of body weight) or matching placebo 48
      hours apart. The primary outcome was death or major disability at the age of 2
      years. RESULTS: There was no significant between-group difference in the rates of
      the primary outcome, which occurred in 686 of 1759 infants (39.0%) who received
      intravenous immune globulin and in 677 of 1734 infants (39.0%) who received
      placebo (relative risk, 1.00; 95% confidence interval, 0.92 to 1.08). Similarly,
      there were no significant differences in the rates of secondary outcomes,
      including the incidence of subsequent sepsis episodes. In follow-up of 2-year-old
      infants, there were no significant differences in the rates of major or nonmajor
      disability or of adverse events. CONCLUSIONS: Therapy with intravenous immune
      globulin had no effect on the outcomes of suspected or proven neonatal sepsis.

PMID- 21962225
TI  - A 10,000-fold nuclear hyperpolarization of a membrane protein in the liquid phase
      via a solid-state mechanism.
AB  - Several techniques rely on electron-nuclear interactions to boost the
      polarization of nuclear spins in the solid phase. Averaging out of anisotropic
      interactions as a result of molecular tumbling strongly reduces the applicability
      of such hyperpolarization approaches in liquids. Here we show for the first time
      that anisotropic electron-nuclear interactions in solution can survive
      sufficiently long to generate nuclear spin polarization by the solid-state photo
      CIDNP mechanism. A 10,000-fold NMR signal increase in solution was observed for a
      giant biomolecular complex of a photosynthetic membrane protein with a tumbling
      correlation time in the submicrosecond regime, corresponding to a molecular
      weight close to 1 MDa.

PMID- 21962224
TI  - Clinical use of a modified release methylphenidate in the treatment of childhood
      attention deficit hyperactivity disorder.
AB  - Attention deficit hyperactivity disorder (ADHD) is the most commonly diagnosed
      neurobehavioural disorder in childhood, affecting over 5% of children worldwide.
      As well as the core symptoms of inattention, hyperactivity and impulsivity,
      patients often exhibit learning difficulties and impairment in social
      functioning. The frequency of referral is higher for boys than for girls (about
      2:1), and girls are generally older at the time of referral.Pharmacological
      therapy is considered the first-line treatment for patients with severe ADHD and
      severe impairment. Stimulant medications are licensed in the UK for the
      management of ADHD in school-age children and young people, and are effective in
      controlling ADHD symptoms.While immediate-release preparations of methylphenidate
      (MPH) have proven effective in the treatment of ADHD, there are a number of
      problems associated with their use, most notably compliance, stigma and
      medication diversion. Modified release preparations are now available that
      overcome the need for multiple daily dosing, and which offer different MPH
      release profiles, thereby enabling the physician to match the medication to the
      patient's particular requirements.This review describes the diagnosis, referral
      and treatment pathways for patients with ADHD in the UK and the practical
      considerations when initiating pharmacological treatment. The clinical experience
      of treating ADHD with a modified-release MPH preparation (Equasym XL(r)) is
      illustrated with case studies.

PMID- 21962226
TI  - Synthesis of alpha-CF3-substituted carbonyl compounds with relative and absolute
      stereocontrol using electrophilic CF3-transfer reagents.
AB  - Evans-type chiral lithium imide enolates undergo diastereoselective alpha
      trifluoromethylation with a hypervalent iodine-CF(3) reagent with up to 91%
      combined isolated yield and 97:3 dr. The resulting isolated diastereopure
      products can be further transformed into valuable products without racemization.

PMID- 21962227
TI  - Dietary intake and eating behavior after bariatric surgery: threats to weight
      loss maintenance and strategies for success.
AB  - During the past decade, bariatric surgery has become an increasingly popular
      treatment option for the growing number of individuals with extreme obesity. For
      most individuals, the size and durability of the weight loss and improvements in
      co-morbidity and mortality have far surpassed those typically seen with
      behavioral modification and pharmacotherapy. A significant minority of patients,
      however, will experience suboptimal outcomes, including less than expected weight
      loss, premature weight regain, and frequent vomiting and/or gastric dumping. The
      reasons for these outcomes are not well understood, but likely involve both
      behavioral and physiologic processes. The present review highlights current
      knowledge on the changes in dietary intake and eating behavior that occur after
      bariatric surgery in terms of the potential threats these changes might pose to
      long-term postoperative success. The paper also identifies several strategies
      from the nonsurgical weight loss literature that might help optimize long-term
      weight maintenance after surgery.

PMID- 21962228
TI  - Organic modification and subsequent biofunctionalization of porous anodic alumina
      using terminal alkynes.
AB  - Porous anodic alumina (PAA) is a well-defined material that has found many
      applications. The range of applications toward sensing and recognition can be
      greatly expanded if the alumina surface is covalently modified with an organic
      monolayer. Here, we present a new method for the organic modification of PAA
      based on the reaction of terminal alkynes with the alumina surface. The reaction
      results in the the formation of a monolayer within several hours at 80  degrees C
      and is dependent on both oxygen and light. Characterization with X-ray
      photoelectron spectroscopy and infrared spectroscopy indicates formation of a
      well-defined monolayer in which the adsorbed species is an oxidation product of
      the 1-alkyne, namely, its alpha-hydroxy carboxylate. The obtained monolayers are
      fairly stable in water and at elevated temperatures, as was shown by monitoring
      the water contact angle. Modification with 1,15-hexadecadiyne resulted in a
      surface that has alkyne end groups available for further reaction, as was
      demonstrated by the subsequent reaction of N-(11-azido-3,6,9
      trioxaundecyl)trifluoroacetamide with the modified surface. Biofunctionalization
      was explored by coupling 11-azidoundecyl lactoside to the surface and studying
      the subsequent adsorption of the lectin peanut agglutinin (PNA) and the yeast
      Candida albicans, respectively. Selective and reversible binding of PNA to the
      lactosylated surfaces was demonstrated. Moreover, PNA adsorption was higher on
      surfaces that exposed the beta-lactoside than on those that displayed the alpha
      anomer, which was attributed to surface-associated steric hindrance. Likewise,
      the lactosylated surfaces showed increased colonization of C. albicans compared
      to unmodified surfaces, presumably due to interactions involving the cell wall
      beta-glucan. Thus, this study provides a new modification method for PAA surfaces
      and shows that it can be used to induce selective adsorption of proteins and
      microorganisms.

PMID- 21962229
TI  - Use of complementary and alternative medicine among US adults with and without
      functional limitations.
AB  - PURPOSE: This study characterizes the use of complementary and alternative
      medicine (CAM) among adults with and without functional limitations. We also
      examine the reasons for using CAM and for disclosing its use to conventional
      medical professionals. METHODS: Data were obtained from the 2007 adult CAM
      supplement and components of the National Health Interview Survey (n = 20,710).
      RESULTS: Adults with functional limitations used CAM more frequently than those
      without (48.7% vs. 35.4%; p < 0.001). Adults with functional limitations used
      mind-body therapies the most (27.4%) and alternative medical systems the least
      (4.8%). Relaxation techniques were the most common therapy used by adults with
      functional limitations, and they used it more often than those without
      limitations (24.6% vs. 13.7%; P < 0.001). More than half of the adults with
      functional limitations (51.3%) discussed CAM use with conventional medical
      professionals, compared with 37.9% of adults without limitations (p < 0.001). The
      main reason for CAM use was general wellness/disease prevention among adults with
      and without functional limitations (59.8% vs. 63.1%; P = 0.051). CONCLUSIONS: CAM
      use among adults with functional limitations is high. Health practitioners should
      screen for and discuss the safety and efficacy of CAM when providing health care.

PMID- 21962231
TI  - Variability and specificity associated with environmental methamphetamine
      sampling and analysis.
AB  - This study was designed to explore the efficacy of the use of wipe sampling to
      determine methamphetamine contamination associated with the clandestine
      manufacture of methamphetamine. Three laboratories were utilized to analyze wipe
      samples to investigate variability in reported methamphetamine concentration
      among samples spiked with known amounts of methamphetamine. Different sampling
      media, surfaces, and solvents were also utilized to determine potential
      differences in measured methamphetamine concentration due to different wipes,
      wipe solvents, and wipe contaminants. This study examined rate of false positive
      detection among blank samples and whether interference with common household
      substances would create a false positive detection of methamphetamine.
      Variability between the three labs-using liquid chromatography with mass
      spectrometry or gas chromatography with mass spectrometry for detection of a
      known concentration of methamphetamine-resulted in percent differences of 3-30%.
      Results from wipe sample analysis for methamphetamine, using methanol or
      isopropanol, showed no significant difference in methamphetamine contamination
      recovery. Dust and paint contamination on methamphetamine wipe samples with known
      methamphetamine spike amounts did not affect methamphetamine wipe sample
      recovery. This study confirmed that either methanol or isopropanol is an
      appropriate solvent for use in methamphetamine wipe sampling. Dust and paint
      contamination on wipe samples will not interfere with the wipe sample analysis
      for methamphetamine. False positive detection for methamphetamine was not
      observed in any of the blank wipe samples submitted for the study. Finally, this
      study determined that methamphetamine will not be detected in structures that are
      truly methamphetamine free at current laboratory limits of quantification.

PMID- 21962230
TI  - MiR-185 targets the DNA methyltransferases 1 and regulates global DNA methylation
      in human glioma.
AB  - BACKGROUND: Perturbation of DNA methylation is frequent in cancers and has
      emerged as an important mechanism involved in tumorigenesis. To determine how DNA
      methylation is modified in the genome of primary glioma, we used Methyl-DNA
      immunoprecipitation (MeDIP) and Nimblegen CpG promoter microarrays to identify
      differentially DNA methylation sequences between primary glioma and normal brain
      tissue samples. METHODS: MeDIP-chip technology was used to investigate the whole
      genome differential methylation patterns in glioma and normal brain tissues.
      Subsequently, the promoter methylation status of eight candidate genes was
      validated in 40 glioma samples and 4 cell lines by Sequenom's MassARRAY system.
      Then, the epigenetically regulated expression of these genes and the potential
      mechanisms were examined by chromatin immunoprecipitation and quantitative real
      time PCR. RESULTS: A total of 524 hypermethylated and 104 hypomethylated regions
      were identified in glioma. Among them, 216 hypermethylated and 60 hypomethylated
      regions were mapped to the promoters of known genes related to a variety of
      important cellular processes. Eight promoter-hypermethylated genes (ANKDD1A,
      GAD1, HIST1H3E, PCDHA8, PCDHA13, PHOX2B, SIX3, and SST) were confirmed in primary
      glioma and cell lines. Aberrant promoter methylation and changed histone
      modifications were associated with their reduced expression in glioma. In
      addition, we found loss of heterozygosity (LOH) at the miR-185 locus located in
      the 22q11.2 in glioma and induction of miR-185 over-expression reduced global DNA
      methylation and induced the expression of the promoter-hypermethylated genes in
      glioma cells by directly targeting the DNA methyltransferases 1. CONCLUSION:
      These comprehensive data may provide new insights into the epigenetic
      pathogenesis of human gliomas.

PMID- 21962233
TI  - Scoliotic posture as the initial symptom in adolescents with lumbar disc
      herniation: its curve pattern and natural history after lumbar discectomy.
AB  - BACKGROUND: There have been few studies focusing on the curve pattern of
      scoliosis caused by lumbar disc herniation (LDH) in adolescents and the natural
      history of scoliosis after discectomy. The current study was carried out to
      identify the curve pattern of scoliosis and investigate the effect of posterior
      discectomy on the curve improvement in adolescents with LDH. METHODS: This review
      focused on a group of 26 adolescents with LDH who initially presented to our
      clinic for evaluation of scoliosis, followed by posterior discectomy between 2000
      and 2009. Radiographic measurements included curve pattern, specific curve
      features, trunk shift, and sagittal profile. The correlation between the side of
      disc herniation and the direction of lumbosacral curve and the trunk shift was
      evaluated. RESULTS: A typical curve pattern was initially identified in all of
      the patients as a short lumbosacral curve accompanied with a long thoracic or
      thoracolumbar curve toward the opposite side. 23 of 26 patients (88.5%) had a
      trunk shift more than 2.0 cm away from the midline, showing a poor coronal
      balance. A relatively straight sagittal profile was noted in all the patients.
      84.6% (22/26) patients had a disc herniation at the convex side of lumbosacral
      curve. Similarly, 73.1% (19/26) patients showed a trunk shift toward the opposite
      side of disc herniation. All of the patients had an marked curve improvement
      immediately after discectomy. In the 17 patients with a more than 2-year follow
      up, only two had a residual lumbosacral curve greater than or equal to 20
      degrees. The mean ODI improved from 21.4% before surgery to 7.3% at the final
      follow-up. CONCLUSIONS: A short lumbosacral curve accompanied with a long
      thoracic or thoracolumbar curve toward the opposite side, and a relatively
      straight sagittal profile have been noted in all the patients. The direction of
      lumbosacral curve and trunk shift was related to the side of disc herniation. A
      majority of patients have a small curve size while assosiated with a significant
      coronal imbalance. Earlier decompression can provide a greater opportunity for
      spontaneous correction of scoliosis.

PMID- 21962234
TI  - Atomistic simulations of electroporation in water preembedded membranes.
AB  - Atomistic simulations of electroporation were conducted on water/membrane/water
      systems, in which the membranes initially contained randomly distributed water
      molecules that might be introduced by acoustic treatment. The simulation results
      indicate that the critical strength of an applied electric field to induce
      electroporation is greatly reduced due to the initially embedded water molecules
      in the membranes. A lower applied electric field will significantly enhance the
      viability of cells in electroporation.

PMID- 21962236
TI  - Cardiac and vascular structure and function parameters do not improve with
      alternate nightly home hemodialysis: an interventional cohort study.
AB  - BACKGROUND: Nightly extended hours hemodialysis may improve left ventricular
      hypertrophy and function and endothelial function but presents problems of
      sustainability and increased cost. The effect of alternate nightly home
      hemodialysis (NHD) on cardiovascular structure and function is not known.
      METHODS: Sixty-three patients on standard hemodialysis (SHD: 3.5-6 hours/session,
      3-5 sessions weekly) converted to NHD (6-10 hours/session overnight for 3-5
      sessions weekly). 2Dimensional transthoracic echocardiography and ultrasound
      measures of brachial artery reactivity (BAR), carotid intima-media thickness
      (CIMT), total arterial compliance (TAC) and augmentation index (AIX) were
      performed post dialysis at baseline and 18-24 months following conversion to NHD.
      In 37 patients, indices of oxidative stress: plasma malonyldialdehyde (MDA) and
      anti-oxidant enzymes: catalase (CAT), glutathione peroxidase (GPX) and superoxide
      dismutase (SOD) activity and total antioxidant status (TAS) were measured at
      baseline, 3 and 6 months. RESULTS: Left ventricular mass index (LVMI) remained
      stable. Despite significant derangement at baseline, there were no changes in
      diastolic function measures, CIMT, BAR and TAC. AIX increased. Conversion to NHD
      improved bone mineral metabolism parameters and blood pressure control.
      Interdialytic weight gains increased. No definite improvements in measures of
      oxidative stress were demonstrated. CONCLUSIONS: Despite improvement in uremic
      toxin levels and some cardiovascular risk factors, conversion to an alternate
      nightly NHD regimen did not improve cardiovascular structure and function.
      Continuing suboptimal control of uremic toxins and interdialytic weight gains may
      be a possible explanation. This study adds to the increasing uncertainty about
      the nature of improvement in cardiovascular parameters with conversion to
      intensive hemodialysis regimens. Future randomized controlled trials will be
      important to determine whether increases in dialysis session duration, frequency
      or both are most beneficial for improving cardiovascular disease whilst
      minimizing costs and the impact of dialysis on quality of life.

PMID- 21962238
TI  - Phosphate: the new cholesterol? The role of the phosphate axis in non-uremic
      vascular disease.
AB  - Higher serum phosphate levels within the normal range are associated with
      substantially increased risk of cardiovascular disease events. Whether this
      reflects a causative relationship is unknown. Phosphate-responsive hormones
      (fibroblast growth factor-23, parathyroid hormone and calcitriol) are also
      predictors of cardiovascular mortality in populations without kidney disease or
      recognised disturbances of bone mineral metabolism. The high bioavailable
      phosphate content of Western diets may contribute to this apparent discrepancy
      between 'normal' and optimal phosphate axis parameters. Although uremic
      hyperphosphatemia is recognised to cause vascular medial calcification, this does
      not readily explain the association of higher-normal phosphate with common athero
      occlusive phenomena. The phosphate axis may in fact play a role in atherogenesis;
      observational data link higher levels of phosphate and fibroblast growth factor
      23 with coronary atheroma burden, whilst dietary phosphate supplementation
      accelerates atherosclerosis in a mouse model. In vitro studies show adverse
      effects of phosphate increases on both vascular smooth muscle cells and
      endothelium, though these observations have not yet been extended to phosphate
      increments within the normal range. Receptors for phosphate-responsive hormones
      are present throughout the cardiovascular system and may mediate atherogenic
      effects. Since interventions are already available to manipulate the phosphate
      axis, this is an important issue. If an atherogenic role for phosphate exposure
      is demonstrated then phosphate binders could become the new statins.

PMID- 21962237
TI  - Inhibition of TLR8- and TLR4-induced Type I IFN induction by alcohol is different
      from its effects on inflammatory cytokine production in monocytes.
AB  - BACKGROUND: Prolonged alcohol consumption is a significant co-factor in the
      progression of chronic viral infections including hepatitis C and HIV, which are
      both single-stranded RNA viruses. Toll like receptor 8 (TLR8), a pattern
      recognition receptor expressed in monocytes, senses viral single stranded RNA as
      a danger signal and leads to the induction of Type I interferon (IFN) as well as
      the pro-inflammatory cytokine, tumor necrosis factor alpha (TNF alpha).
      Lipopolysaccharide (LPS), a Toll like receptor 4 (TLR4) ligand, was shown to
      affect inflammatory cell activation after alcohol consumption and in HIV and HCV
      infections. Here we hypothesized that alcohol exposure modulates TLR8- and TLR4
      ligand-induced monocyte activation and affects both type I IFN and inflammatory
      cytokine induction. RESULTS: The TLR8 ligand, CL075, as well as the TLR4 ligand,
      LPS, resulted in a significant induction of TNF alpha both at the mRNA and
      protein levels in human monocytes. We found that both acute and prolonged alcohol
      treatment resulted in inhibition of type I IFN induction by either TLR8 or TLR4
      ligands in human monocytes at the protein and mRNA levels. In contrast to Type I
      IFN production, the effects of acute and prolonged alcohol were different on
      inflammatory cytokine activation after TLR8 or TLR4 ligand stimulation. Acute
      alcohol inhibited TLR8- or TLR4-induced TNF alpha protein and mRNA induction
      while it augmented IL-10 production in monocytes. In contrast, prolonged alcohol
      treatment augmented TNF alpha without affecting IL-10 production significantly in
      response to either TLR8 or TLR4 ligand stimulation. CONCLUSIONS: These novel
      results suggest first, that alcohol has a profound inhibitory effect on Type I
      IFN induction regardless of intracellular (TLR8) or cell surface-derived (TLR4)
      danger signals. Second, both acute and prolonged alcohol exposure can inhibit
      antiviral Type I IFN pathway activation. Third, the opposite effects of acute
      (inhibitory) and prolonged alcohol (augmentation) treatment on pro-inflammatory
      cytokine activation extend to TLR8-induced signals beyond the previously shown
      TLR4/LPS pathway.

PMID- 21962239
TI  - Increased levels of circulating cytokines with HIV-related immunosuppression.
AB  - Cytokines may contribute to the severity of CD4 cell depletion with human
      immunodeficiency virus (HIV) infection, but quantitative relationships are not
      well defined. Serum and plasma from 181 HIV-infected individuals were tested with
      Millipore 30-plex Luminex cytokine assays. Within-individual correlations among
      cytokines were summarized by two-dimensional hierarchical cluster analysis.
      Associations with age, sex, race, CD4 count, and HIV viral load were determined
      with linear regression models. Tests for statistical significance were corrected
      for multiple comparisons, using a false discovery rate of 0.1. African-Americans
      had significantly higher levels than whites of six cytokines (IL-2, IL-5, IL-7,
      IL-15, fractalkine, and IFN-gamma), and lower levels of MCP-1. Females had higher
      fractalkine levels than males. Age was not associated with levels of any
      cytokine. Six cytokines, including the T-helper (Th) type 1 cytokine IL-15, the
      Th2 cytokines IL-1ra and IL-10, the chemokines fractalkine and MCP-1, and the
      growth factor G-CSF were each inversely associated with CD4 count; no cytokine
      was directly associated with CD4 count. Fractalkine was directly associated with
      HIV viral load, adjusted for CD4 count. Cytokines clustered by primary function
      (e.g., Th1, Th2, proinflammatory, chemokines, or growth factors) whereas
      individuals clustered according to cytokine levels (generally high, intermediate,
      or low) had significantly different CD4 counts [medians (interquartile range) of
      60 (17-162), 131 (62-321), and 155 (44-467), respectively; p<0.0001]. CD4
      deficiency is associated with generalized increases in cytokines of various
      functions. Racial differences in cytokine response to HIV infection could
      contribute to disparities in disease progression.

PMID- 21962240
TI  - [Paraneoplastic neurological syndrome associated with anti-Ma2 antibodies].

PMID- 21962242
TI  - Surface effects on the demixing of colloid-polymer systems.
AB  - We studied the effect of a solid surface on the fluid-fluid phase separation of a
      colloid-polymer mixture in real space, exploring demixing from both the unstable
      and metastable regions of the phase diagram. The presence of a wall breaks the
      symmetry of the phase separation morphology in the direction perpendicular to the
      surface, influencing the coarsening behavior of domains. We analyzed the
      thickening of the wetting layers and found that hydrodynamic transport processes
      can significantly increase the rate of wetting-layer growth. Depending on the
      volume ratio between the two phases, a new regime was observed in which the
      demixing structure disconnected from the wall, but remained bicontinuous in the
      bulk. We also discuss the effect of a crossover in the demixing regime of bulk
      domains on the growth of this layer.

PMID- 21962241
TI  - Fluvoxamine may prevent onset of psychosis: a case report of a patient at ultra
      high risk of psychotic disorder.
AB  - BACKGROUND: There is emerging evidence that antidepressants may be effective in
      preventing patients with non-specific and psychotic-like prodromal symptoms,
      defined as patients at ultra-high risk (UHR) of psychotic disorder, from
      transitioning to psychosis. However, the mechanism of such an effect is still
      unknown. METHODS: We report the case of a 19-year-old Japanese man determined to
      be at UHR of psychotic disorder in whom fluvoxamine (one of the antidepressants
      with sigma-1 receptor agonism) showed preventive effects on psychotic-like
      prodromal symptoms. RESULTS: Our patient's depressive symptoms were reduced and
      maintained below remission as a result of treatment with 100 mg/day of
      fluvoxamine. In addition, it is likely that an additional dose of fluvoxamine (50
      mg/day) improved his psychotic-like prodromal symptoms directly, independent of
      its antidepressive effects. CONCLUSION: Fluvoxamine, a sigma-1 receptor agonist,
      may be effective in preventing patients at UHR of psychotic disorder from onset
      of psychosis via its neuroprotective/neurotropic actions, independent of its
      antidepressive effects.

PMID- 21962243
TI  - Two-dimensional 1H HYSCORE spectroscopy of dimanganese di-MU-oxo mimics of the
      oxygen-evolving complex of photosystem II.
AB  - The solar water-splitting protein complex, photosystem II, catalyzes one of the
      most energetically demanding reactions in nature by using light energy to drive
      water oxidation. The four-electron water oxidation reaction occurs at the
      tetranuclear manganese-calcium-oxo cluster that is present in the oxygen-evolving
      complex of photosystem II. The tetranuclear manganese-calcium-oxo cluster is
      comprised of mixed-valence Mn(III) and Mn(IV) ions in the ground state. The oxo
      manganese dimer, [H(2)O(terpy)Mn(III)(MU-O)(2)Mn(IV)(terpy)OH(2)](NO(3))(3)
      (terpy = 2,2':6',2"-terpyridine) (1), is an excellent biomimetic model that has
      been extensively used to gain insight on the molecular structure and mechanism of
      water oxidation in photosystem II. In this work, weak magnetic interactions
      between the protons of the two terminal water ligands and the paramagnetic
      dimanganese "di-MU-oxo" core of 1 are quantitatively characterized using two
      dimensional hyperfine sublevel correlation (HYSCORE) spectroscopy. For the water
      molecule that is directly coordinated at the Mn(III) ion, the two protons are
      found to be magnetically equivalent and exhibit near axial hyperfine anisotropy.
      In contrast, for the first time, we demonstrate that the two protons of the water
      molecule that is directly coordinated at the Mn(IV) ion are inequivalent. We
      obtain the isotropic and anisotropic components of the hyperfine interaction for
      each proton. A comparison of the HYSCORE spectra measured in the presence and
      absence of acetate ions provides unambiguous evidence that only one molecule of
      acetate binds to 1 by replacing a terminal water molecule that is coordinated at
      the Mn(III) ion.

PMID- 21962245
TI  - An inconvenient truth behind high accessibility to medical services.

PMID- 21962244
TI  - Targeting HSP90 in ovarian cancers with multiple receptor tyrosine kinase
      coactivation.
AB  - BACKGROUND: Ovarian cancer has the highest mortality rate of all gynecologic
      malignancy. The receptor tyrosine kinases (RTKs), including EGFR, ERBB2, PDGFR,
      VEGFR and MET, are activated in subsets of ovarian cancer, suggesting that these
      kinases might represent novel therapeutic targets. However, clinical trials have
      not or just partially shown benefit to ovarian cancers treated with EGFR, ERBB2,
      or PDGFR inhibitors. Despite multiple RTK activation in ovarian cancer
      pathogenesis, it is unclear whether transforming activity is dependent on an
      individual kinase oncoprotein or the coordinated activity of multiple kinases. We
      hypothesized that a coordinated network of multi-RTK activation is important for
      the tumorigenesis of ovarian cancers. RESULTS: Herein, we demonstrate co
      activation of multiple RTKs (EGFR, ERBB2, ERBB4, MET and/or AXL) in individual
      ovarian cancer cell lines and primary tumors. We also show that coordinate
      inhibition of this multi-kinase signaling has substantially greater effect on
      ovarian cancer proliferation and survival, compared to inhibition of individual
      activated kinases. The inhibition of this multi-RTK signaling by HSP90
      suppression results in profound pro-apoptotic and anti-proliferative effects, and
      is associated with the inactivation of RTK downstream PI3-K/AKT/mTOR and RAF/MAPK
      signaling. CONCLUSION: These studies suggest that anti-multiple RTK strategy
      could be useful in the treatment of ovarian cancer.

PMID- 21962246
TI  - Kinetics of cytokine expression in cirrhotic rats.
AB  - BACKGROUND: Cytokines are involved in liver injury and cirrhosis and systemic and
      hepatic cytokine levels may help predict cirrhosis evolution. However, the
      relevant survey has not been performed. METHODS: Male Sprague-Dawley rats (240
      270 g) received either common bile duct ligation (BDL, animal model of
      cholestatic liver injury) or sham operation (control). Five rats were sacrificed
      and liver and serum were collected from each in weeks 1, 2, 4, 6, 8 and 10 after
      surgery. Hepatic expression of interferon-gamma (IFN-gamma), tumor necrosis
      factor-alpha (TNF-alpha), interleukin-10 (IL-10) and transforming growth factor
      beta (TGF-beta) were analyzed by immunohistochemial staining. The corresponding
      serum levels were measured by ELISA. RESULTS: Compared to the corresponding sham
      groups, hepatic expression of these cytokines in BDL rats was significantly and
      progressively enhanced during cirrhosis development. However, serum IFN-gamma
      levels of BDL rats did not change significantly. Serum TNF-alpha of BDL rats
      increased gradually and reached a peak in week 6. Serum TGF-beta level was
      elevated up to week 8, whereas IL-10 level decreased progressively until week 6.
      CONCLUSION: Cirrhosis development in BDL rats is associated with progressively
      enhanced expression of hepatic pro-inflammatory and anti-inflammatory cytokines,
      which is not in accord with the corresponding serum concentration. The
      circulating cytokine concentration may not totally reflect the hepatic expression
      level throughout the development of cirrhosis.

PMID- 21962247
TI  - Lack of direct effects of acyl ghrelin, des-acyl ghrelin, and obestatin on rat
      lower esophageal sphincter motility in vitro.
AB  - BACKGROUND: Three ghrelin gene-derived peptides, acyl ghrelin, des-acyl ghrelin
      and obestatin, are implicated in the regulation of feeding, adipogenesis and
      glucose metabolism, as well as gut motility. The effects of ghrelin gene-derived
      peptides on lower esophageal sphincter motility, however, were unknown. METHODS:
      We investigated the influence of acyl ghrelin, des-acyl ghrelin and obestatin on
      lower esophageal sphincter motility using the in vitro isolated muscle strip
      method. Both resting and carbachol-stimulated rat lower esophageal sphincters
      were tested. RESULTS: Acyl ghrelin, des-acyl ghrelin and obestatin did not alter
      the resting tone of the lower esophageal sphincter, whereas carbachol increased
      the force of the muscle strips. Similarly, acyl ghrelin, des-acyl ghrelin and
      obestatin did not modify carbachol-induced stimulation of the lower esophageal
      sphincter, whereas papaverine significantly decreased the force of the muscle
      strips. CONCLUSION: Since the contractile effects of carbachol and relaxant
      responses of papaverine on the lower esophageal sphincter were confirmed, our
      results demonstrate that acyl ghrelin, des-acyl ghrelin and obestatin have no
      direct effects on rat lower esophageal sphincter motility in vitro.

PMID- 21962248
TI  - Nonmucosa-associated lymphoid tissue lymphomas of gastric and intestinal origin
      differ in their clinical features: a single institute experience.
AB  - BACKGROUND: The treatment policy and disease process of mucosa-associated
      lymphoid tissue (MALT) lymphomas are different from those of other
      gastrointestinal lymphomas. Chemotherapy has replaced curative surgery as the
      treatment of choice in gastric lymphomas but the optimal frontline treatment of
      intestinal lymphomas has yet to be defined. Hence, we attempted to identify the
      difference in features between gastric and intestinal nonMALT lymphomas. METHODS:
      Patients who were newly diagnosed with nonMALT lymphomas of gastrointestinal
      origin in our hospital between January 2001 and February 2010 were included in
      our study. Patient characteristics and outcomes were retrospectively analyzed.
      RESULTS: Among 59 gastric lymphoma patients and 25 intestinal lymphoma patients,
      the intestinal group were significantly younger and had better performance
      (p=0.002 and 0.042). Whereas gastrointestinal obstruction and intussusception
      were more common in the intestinal group (p=0.024 and 0.024), more bleeding
      episodes were displayed in the gastric counterpart (p=0.042). Histologically,
      diffuse large B-cell lymphoma was more prevalent in the stomach, and enteropathy
      associated T-cell lymphoma was found only in the intestine (p=0.006 and 0.024).
      Despite more intestinal lymphoma patients receiving surgery (p=0.002), the
      response rate, overall survival and progression-free survival were similar to the
      gastric counterpart (p=0.1060, 0.7758 and 0.1248). In the multivariate analysis
      of overall survival, chemotherapy (hazard ratio [HR] 0.2; 95% confidence interval
      [CI] 0.091-0.440; p<0.001) and International Prognostic Index (HR 1.7; 95% CI
      1.181-2.448; p=0.004) proved prognostic in gastric lymphomas. Furthermore, T-cell
      lineage (HR 8.615; 95% CI 2.165-34.288; p=0.002) and poor performance (HR 9.374;
      95% CI 1.497-58.712; p=0.017) were poor predictors in the intestinal counterpart.
      CONCLUSION: Intestinal lymphomas differ from gastric lymphomas in manifestation,
      histology, management and prognosis. Surgery still plays a role in intestinal
      lymphomas because presentations of surgical emergencies are more common. In
      addition, the outcome of gastric lymphomas compared with intestinal lymphomas is
      no longer superior if patients with MALT lymphomas are excluded. Because of the
      limited number of enrolled patients, further large-scale studies are warranted to
      validate these results.

PMID- 21962249
TI  - The ecology of medical care in Taiwan.
AB  - BACKGROUND: In regular administrative statistics for medical services,
      utilization data are usually presented as aggregate data and lack an individual
      perspective. The aim of this study was to provide an overview of medical care
      utilization in Taiwan using a long-established analytical framework, the so
      called ecology model. METHODS: Claims data for a cohort of one million people
      from the National Health Insurance (NHI) Research Database were used to estimate
      the yearly and monthly prevalence of health care utilization in Taiwan in 2005.
      Analyses were extended to different types of healthcare settings and were
      stratified by age and sex. Results are presented per 1000 of the population.
      RESULTS: Per 1000 people, 74 did not utilize any NHI services during the year. In
      a month, 503 people on average utilized at least once NHI service of any kind,
      329 visited a physician's clinic (Western medicine), 152 visited a hospital-based
      outpatient clinic, 19 visited an emergency department, 10 were hospitalized and 3
      were hospitalized in an academic medical center. Women were more likely to
      utilize NHI services than men (274/504 vs. 229/496 in a month). In a month on
      average, 40.3% (146/362) of young people, 52.2% (166/318) of middle-aged people,
      53.3% (121/227) of children and 75.0% (70/93) of elderly people utilized NHI
      services. Over the whole year, 22.0% (21/93) of elderly people were hospitalized
      and nearly one-third of them were hospitalized in academic medical centers.
      CONCLUSION: People in Taiwan utilized NHI services frequently and tended to seek
      medical help in hospitals. Although these features might reflect the higher
      availability and accessibility of medical care within the NHI in Taiwan, the
      possibility of overuse deserves further attention.

PMID- 21962250
TI  - Re-evaluation of CO2 laser myringotomy for managing children with persistent
      acute otitis media.
AB  - BACKGROUND: This study aimed to re-evaluate the utility of CO(2) laser
      myringotomy in children with persistent acute otitis media (PAOM). METHODS: From
      September 2002 to April 2008, 40 children with PAOM received CO(2) laser
      myringotomy. PAOM was defined as continuing symptoms and signs after systemic
      antibiotic treatment. Before laser myringotomy, the eardrums were checked under
      videotelescopy, pure tone audiometry or behavior audiometry and tympanometry.
      Middle ear effusions were collected using our own designed bottle culture device
      after laser myringotomy. The patients were followed up at outpatient clinics for
      3 months. Cultured middle ear pathogens, healing time of the eardrums, hospital
      course (for admitted patients), and the development of middle ear effusions were
      recorded. RESULTS: Forty children with 53 ears with PAOM were enrolled. Eight
      patients (20%) had bilateral disease and underwent bilateral laser myringotomy.
      The overall culture rate was 28.3%, and Streptococcus pneumoniae was the most
      common pathogen. Eight patients (20%) were admitted for intravenous antibiotics.
      The average eardrum healing time was 22 days in those with positive cultures, and
      16.4 days in those with negative cultures (p=0.125). All eardrums healed in 1
      month. The resolution rate was 62.5% at 1 month. Patients with bilateral PAOM
      were prone to have positive middle ear culture (5/8) compared with those with
      unilateral PAOM (8/32) (p=0.086). CONCLUSION: CO(2) laser myringotomy is an
      applicable means of treating PAOM. S pneumoniae is the most common pathogen in
      PAOM. CO(2) laser myringotomy allows for the drainage and culture sampling of
      middle ear effusion, relieving the need of taking prolonged medication.

PMID- 21962251
TI  - Chronic graft-versus-host disease complicated by nephrotic syndrome.
AB  - Chronic graft-versus-host disease (cGVHD) is one of the most frequent and serious
      complications of allogeneic hematopoietic stem cell transplantation (HSCT).
      Nephrotic syndrome (NS) is an uncommon and underrecognized manifestation of
      cGVHD. We report a patient who developed NS 18 months after allogeneic bone
      marrow transplantation. The onset of NS was accompanied by active manifestations
      of cGVHD, and immunosuppressants had not been tapered recently. Renal biopsy
      revealed membranous nephropathy. The patient failed to improve with three
      combined immunosuppressants (prednisolone, cyclosporine, and mycophenolate
      mofetil), but achieved partial remission after intravenous immunoglobulin (IVIG)
      infusion. Twenty-four months after the diagnosis of NS, the patient was still in
      hematological remission, with normal serum creatinine level, urinary protein loss
      of 0.7-1.9 g/day and mild oral mucositis. Our report suggests that NS can be a
      cGVHD-related immune disorder in HSCT patients. Monitoring of renal parameters,
      especially proteinuria, is important in cGVHD patients. Our case indicated that
      post-transplant NS, occurring without history of tapering or following
      immunosuppressant withdrawal, presents a more severe activity of cGVHD and a
      relatively severe clinical course. IVIG may modify and control the refractory
      GVHD-related NS, and can be one of the choices of treatment.

PMID- 21962252
TI  - Hemopericardium from right atrial laceration in a newborn.
AB  - We report the case of a newborn who suffered right atrial laceration during
      delivery. To our knowledge, there has been no previous report of blunt injury
      causing right atrial laceration with hemopericardium complicated by cardiac
      tamponade in the perinatal period.

PMID- 21962253
TI  - Acute immune thrombocytopenic purpura in an adolescent with 2009 novel H1N1
      influenza A virus infection.
AB  - Although both leukopenia and thrombocytopenia are not uncommon hematological
      findings among patients with novel 2009 H1N1 influenza virus infection, immune
      thrombocytopenic purpura has rarely been shown to be associated with this novel
      influenza A infection. Here, we describe a previously healthy adolescent who
      presented with fever, influenza-like symptoms and acute onset of generalized
      petechiae and active oral mucosa bleeding on the third day of his illness. Severe
      leukopenia and thrombocytopenia were found. There was neither malignancy nor
      blast cells found by bone marrow aspiration. Real-time reverse transcriptase
      polymerase chain reaction was positive for novel 2009 H1N1 influenza infection.
      Novel influenza-associated atypical immune thrombocytopenic purpura was
      diagnosed. The patient recovered uneventfully after oseltamivir and
      methylprednisolone therapy.

PMID- 21962255
TI  - Eawag at 75.

PMID- 21962254
TI  - Iterative in situ click chemistry assembles a branched capture agent and
      allosteric inhibitor for Akt1.
AB  - We describe the use of iterative in situ click chemistry to design an Akt
      specific branched peptide triligand that is a drop-in replacement for monoclonal
      antibodies in multiple biochemical assays. Each peptide module in the branched
      structure makes unique contributions to affinity and/or specificity resulting in
      a 200 nM affinity ligand that efficiently immunoprecipitates Akt from cancer cell
      lysates and labels Akt in fixed cells. Our use of a small molecule to preinhibit
      Akt prior to screening resulted in low micromolar inhibitory potency and an
      allosteric mode of inhibition, which is evidenced through a series of competitive
      enzyme kinetic assays. To demonstrate the efficiency and selectivity of the
      protein-templated in situ click reaction, we developed a novel QPCR-based
      methodology that enabled a quantitative assessment of its yield. These results
      point to the potential for iterative in situ click chemistry to generate potent,
      synthetically accessible antibody replacements with novel inhibitory properties.

PMID- 21962256
TI  - Discrepancies in the concordance of self-reported vision status and visual acuity
      in the Salisbury Eye Evaluation Study.
AB  - PURPOSE: To examine the association between self-rated vision and distance visual
      acuity by race and other factors. DESIGN: Cross-sectional analysis within a
      longitudinal, population-based cohort study. PARTICIPANTS AND CONTROLS: Two
      thousand five hundred twenty individuals, 65 to 84 years of age, including 666
      black participants and 1854 white participants. METHODS: All participants
      reported their self-rated vision score. Binocular distance visual acuity was
      assessed. Based on the level of visual acuity and the self-reported vision score,
      participants were placed into concordant and discrepant groups. MAIN OUTCOME
      MEASURES: Multinomial logistic regression models were used to examine the
      characteristics associated with concordant and discrepant groups. RESULTS: Black
      participants were more likely to be represented in the discordant group that
      reported good vision but had acuity worse than 20/40. In the multivariate
      analysis, a per-year decrement in years of education received increased the odds
      of being in both discrepant groups, one that reported good vision but had a
      visual acuity worse than 20/40 (odds ratio, 1.21; P<0.0001) and the other
      discrepant group that reported bad vision but had a visual acuity of 20/40 or
      better (odds ratio, 1.04; P<0.0001). A per-year decrement in years of education
      received also seemed to explain the excess risk of black race in the discrepant
      group that reported good vision but had a visual acuity worse than 20/40.
      CONCLUSIONS: Given the socioeconomically driven discrepancies in self-reported
      vision status, self-reported vision status should be used cautiously in
      surveillance surveys, especially when assessing vision inequalities between
      socioeconomic groups. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary
      or commercial interest in any materials discussed in this article.

PMID- 21962257
TI  - Synthesis of a bile acid-based click-macrocycle and its application in selective
      recognition of chloride ion.
AB  - A novel method for the synthesis of a bile acid-based macrocycle has been
      developed using click chemistry. The 1,2,3-triazolium derivative of the
      macrocycle shows remarkable selectivity in binding of chloride ion.

PMID- 21962259
TI  - Impact of preoperative renal dysfunction on outcomes of off-pump coronary artery
      bypass grafting.
AB  - BACKGROUND: This study assessed whether preoperative renal insufficiency
      predisposes patients undergoing off-pump coronary artery revascularization to
      postoperative dialysis. METHODS: From August 2004 through June 2009, 2,275
      patients undergoing off-pump coronary artery bypass were categorized into five
      groups (stages) by glomerular filtration rate (GFR). Of these, 1,855 patients had
      renal insufficiency: stage 2: 1,406; stage 3: 428; stage 4: 21, and 414 had
      normal renal function, stage 1. Excluded were 6 patients with end-stage renal
      disease (stage 5). Preoperative variables and postoperative outcomes were
      compared among groups. RESULTS: Preoperative patient characteristics were
      similar; however, patients with normal renal function were younger (p = 0.001).
      Serum creatinine rose significantly above baseline on the first postoperative day
      in the renal insufficiency groups (p = 0.001). The GFR groups had similar
      inotrope use, reexploration rate, duration of postoperative mechanical
      ventilation, postoperative stroke, wound infection, and mortality rate. Stage 4
      patients had a higher incidence of postoperative myocardial infarction (p =
      0.002). Stage 3 and 4 patients had an increased need for postoperative dialysis
      vs stage 1 patients (p = 0.002). CONCLUSIONS: Nonparametric contingency analysis
      showed patients with low preoperative GFR (stage 3 and 4, p < 0.0001) and a
      history of smoking (p = 0.04) were at increased risk for postoperative dialysis.
      Patients who required postoperative inotropic support tended toward requiring
      postoperative dialysis (p = 0.06). Low preoperative ejection fraction (p = 0.83),
      class III or IV angina (p = 0.069), and postoperative blood transfusions were not
      associated with the need for postoperative dialysis in patients undergoing off
      pump revascularization.

PMID- 21962260
TI  - Intraoperative oncologic staging and outcomes for lung cancer resection vary by
      surgeon specialty.
AB  - BACKGROUND: In the United States the majority of lung cancer resections are
      performed by general surgeons, although surgeons specializing in thoracic surgery
      have demonstrated superior perioperative and long-term oncologic outcomes. Why
      these differences exist has not been well studied. We hypothesized that the
      completeness of intraoperative oncologic staging may explain some of these
      differences. METHODS: The Nationwide Inpatient Sample (NIS) database was used to
      review 222,233 patients with primary lung cancer treated surgically with wedge
      resection, segmentectomy, lobectomy, or pneumonectomy from 1998 to 2007. Surgeons
      were classified as general thoracic surgeons if they performed greater than 75%
      general thoracic operations and less than 10% cardiac operations; they were
      classified as cardiac surgeons if they performed greater than 10% cardiac
      operations; they were classified as general surgeons if they performed less than
      75% thoracic operations and less than 10% cardiac operations. The main outcome
      measure was the performance of lymphadenectomy or mediastinoscopy during the same
      admission as the cancer resection. RESULTS: The overall lymphadenectomy rate was
      56% (n = 125,115) and was highest for general thoracic surgeons at 73% (n =
      13,313), followed by 55% (n = 65,453) for general surgeons, and 54% (n = 46,349)
      for cardiac surgeons (p < 0.0001). General surgeons had a significantly higher
      risk for in-hospital mortality (odds ratio [OR], 1.47; confidence interval [CI],
      1.14 to 1.90; p = 0.003) and postoperative complications (OR, 1.17; CI, 1.00 to
      1.36; p = 0.043) compared with general thoracic surgeons. CONCLUSIONS: Surgeon
      specialty impacts the adequacy of oncologic staging in patients undergoing
      resection for primary lung cancer. Specifically, general thoracic surgeons
      performed intraoperative oncologic staging significantly more often than did
      their general surgeon and cardiac surgeon counterparts while achieving
      significantly lower in-hospital mortality and complication rates.

PMID- 21962261
TI  - Early diagnosis of perioperative myocardial infarction after coronary bypass
      grafting: a study using biomarkers and cardiac magnetic resonance imaging.
AB  - BACKGROUND: Myocardial injury related to coronary artery bypass grafting (CABG)
      is poorly characterized, and understanding the characteristic release of
      biomarkers associated with revascularization injury might provide novel
      therapeutic opportunities. This study characterized early changes in biomarkers
      after revascularization injury during on-pump CABG. METHODS: This prospective
      study comprised 28 patients undergoing on-pump CABG and late gadolinium
      enhancement (LGE) cardiac magnetic resonance imaging (CMRI) who underwent
      measurements of cardiac troponin I (cTnI), creatine kinase-MB, and inflammatory
      markers (C-reactive protein, serum amyloid A, myeloperoxidase, interleukin 6,
      tumor necrosis factor-alpha, matrix metalloproteinase 9a, monocyte chemotactic
      protein-1, plasminogen activator inhibitor-1a) at baseline, at 1, 6, 12, and 24
      hours, and at 1 week (inflammatory markers only) post-CABG. Biomarker results at
      1 hour were studied for a relationship to new myocardial infarction as defined by
      CMRI-LGE, and the diagnostic utility of combining positive biomarkers was
      assessed. RESULTS: All patients had an uneventful recovery, but 9 showed a new
      myocardial infarction demonstrated by new areas of hyperenhancement on CMR. Peak
      cTnI at 24 hours (rho = 0.66, p < 0.001) and CK-MB (rho = 0.66, p < 0.001)
      correlated with the amount of new LGE. At 1 hour, 3 biomarkers--cTnI, interleukin
      6, and tumor necrosis factor-alpha--were significantly elevated in patients with
      vs those without new LGE. Receiver operating curve analysis showed cTnI was the
      most accurate at detecting new LGE at 1 hour: a cutoff of cTnI exceeding 5 MUg/L
      at 1 hour had 67% sensitivity and 79% specificity for detecting new LGE.
      CONCLUSIONS: Unexpected CABG-related myocardial injury occurs in a significant
      proportion of patients. A cTnI test at 1 hour after CABG could potentially
      differentiate patients with significant revascularization injury.

PMID- 21962262
TI  - Thymomas and extrathymic cancers.
AB  - BACKGROUND: Patients with thymoma may have a predisposition toward extrathymic
      neoplasia. To understand the lifetime risk and incidence of extrathymic neoplasia
      in patients with thymoma, we evaluated extrathymic neoplasms diagnosed either
      before or after the diagnosis of thymoma. METHODS: We queried the Surveillance,
      Epidemiology, and End Results (SEER) cancer database and identified patients with
      thymoma and extrathymic neoplasms. We collected demographic and treatment data,
      calculated the incidence of each extrathymic neoplasm (adjusting for age), and
      compared the incidence of extrathymic neoplasm in patients with thymoma with the
      age-adjusted incidence in the SEER database general population. RESULTS: Of 2,171
      patients with thymoma in the SEER database, 306 (14.1%) had extrathymic primary
      cancers. Extrathymic neoplasms were diagnosed before the diagnosis of thymoma in
      88 patients and after the diagnosis of thymoma in 206 patients. In 12 patients,
      separate extrathymic neoplasms were diagnosed both before and after thymoma
      diagnosis. The incidence of extrathymic cancers in patients with thymoma (8,224
      per 100,000 persons) was significantly higher than in the SEER general population
      (459 per 100,000 persons; p<0.001). The standardized incidence ratio for
      extrathymic cancer was also significantly increased, in particular for lymphomas,
      leukemias, esophageal cancer, and lung cancer. Increased age at diagnosis
      (p<0.001), longer survival after diagnosis (p<0.001), and male sex (p=0.041)-but
      not radiation therapy or surgery-were significant risk factors for the
      development of extrathymic cancers in patients with thymoma. CONCLUSIONS: The
      incidence of extrathymic neoplasia is significantly higher in patients with
      thymoma than in the general population and occurs both before and after the
      diagnosis of thymoma.

PMID- 21962263
TI  - Does the timing of esophagectomy after chemoradiation affect outcome?
AB  - BACKGROUND: After neoadjuvant chemoradiation (CXRT) for esophageal cancer,
      surgery has traditionally been recommended to be performed within 8 weeks.
      However, surgery is often delayed for various reasons. Data from other cancers
      suggest that delaying surgery may increase the pathologic complete response rate.
      However, there are theoretical concerns that waiting longer after radiation may
      lead to a more difficult operation and more complications. The optimal timing of
      esophagectomy after CXRT is unknown. METHODS: From a prospective database, we
      analyzed 266 patients with resected esophageal cancer who were treated with
      neoadjuvant CXRT from 2002 to 2008. Salvage resections were excluded from this
      analysis. We compared patients who had surgery within 8 weeks of CXRT and those
      who had surgery after 8 weeks. We used multivariable analysis to determine
      whether increased interval between chemoradiation and surgery was independently
      associated with perioperative complication, pathologic response, or overall
      survival. RESULTS: One hundred fifty patients were resected within 8 weeks and
      116 were resected greater than 8 weeks after completing CXRT. Mean length of
      operation, intraoperative blood loss, anastomotic leak rate, and perioperative
      complication rate were similar for the two groups. Pathologic complete response
      rate and overall survival were also similar for the two groups (p=not
      significant). In multivariable analysis, timing of surgery was not an independent
      predictor of perioperative complication, pathologic complete response, or overall
      survival. CONCLUSIONS: The timing of esophagectomy after neoadjuvant CXRT is not
      associated with perioperative complication, pathologic response, or overall
      survival. It may be reasonable to delay esophagectomy beyond 8 weeks for patients
      who have not yet recovered from chemoradiation.

PMID- 21962265
TI  - Late outcome of 132 Senning procedures after 20 years of follow-up.
AB  - BACKGROUND: Risk factors and rates of reoperation, arrhythmias, systemic right
      ventricular dysfunction (RVD), and late death after a Senning procedure were
      investigated. METHODS: One-hundred thirty-two patients underwent a Senning
      operation between 1977 and 2004 (105 simple and 27 complex transpositions of the
      great arteries). Mean follow-up time was 19.5 +/- 6.6 years. Surviving patients
      were evaluated by transthoracic echocardiography and electrocardiography. Right
      ventricular function was assessed in 70 patients by isotopic ventriculography or
      magnetic resonance imaging. RESULTS: Operative and late mortality were 5.3%
      (7/132) and 9.6% (12/125), respectively. Nine patients were reoperated for left
      ventricular outflow tract obstruction or baffle stenosis. Survival rate was
      91.5%, 91%, 89%, and 88% at 1, 5, 10, and 20 years, respectively. Probability of
      maintaining permanent sinus rhythm was 80%, 65%, 55%, and 44%. Twelve patients
      required pacemaker implantation. Probability of no supraventricular tachycardia,
      atrial flutter/fibrillation or ventricular tachycardia was 95.5%, 91.5%, 88%, and
      75%, respectively. These parameters were similar for simple and complex
      transposition. Probability of right ventricular ejection fraction >40% was 100%
      at 5 and 10 years, and 98% at 20 years for simple transposition, and 100%, 92%,
      and 58% for complex transposition. This difference was statistically significant.
      Risk factors for RVD were complex transposition (p < 0.001), body weight (p =
      0.008), no cardioplegia (p < 0.001), and tricuspid valve regurgitation (p =
      0.004). CONCLUSIONS: Senning procedure results in very good long-term survival
      out to 20 years. Both RVD and baffle stenosis were rare, but there was a
      concerning incidence of arrhythmia over time suggesting careful long-term
      surveillance.

PMID- 21962264
TI  - Improved survival but marginal allograft function in patients treated with
      extracorporeal membrane oxygenation after lung transplantation.
AB  - BACKGROUND: Previous reports demonstrate that 1-year survival is severely
      compromised in patients with severe primary graft dysfunction (PGD) after lung
      transplantation. We examined if advances in extracorporeal membrane oxygenation
      (ECMO) support, including polymethylpentene oxygenators and reliance on
      venovenous (VV) ECMO have improved outcomes in patients with severe PGD after
      lung transplantation. METHODS: The analysis included data prospectively collected
      on all single-lung or double-lung transplants between November 2001 and December
      2009. Heart-lung transplants were excluded. Comparisons were made between
      recipients who did and did not require ECMO for PGD after transplant. RESULTS:
      Since November 2001, when VV ECMO became the routine treatment for severe PGD
      after transplant at our center, 28 of 498 patients (6%) have required VV ECMO
      support. Successful weaning occurred in 27 of 28 (96%). Support was withdrawn for
      1 patient with irreversible neurologic injury. Survival was substantially better
      than in previous reports: 30 days, 82%; 1 year, 64%; and 5 years, 49%. Freedom
      from bronchiolitis obliterans syndrome was 88% in the ECMO survivors at 3 years,
      but maximum allograft function was considerably worse than in transplant
      recipients not requiring ECMO (peak forced expiratory volume in 1 second: 58% in
      ECMO vs 83% in non-ECMO, p=0.001). CONCLUSIONS: Advances in ECMO technology,
      particularly VV ECMO, have greatly improved the ability to support patients with
      severe PGD after lung transplantation. VV ECMO is an important tool in the
      armamentarium of any lung transplant program to optimize patient outcomes;
      however, strategies to improve lung allograft function in patients experiencing
      severe PGD are still needed.

PMID- 21962266
TI  - Supra-annular mitral valve replacement in children.
AB  - BACKGROUND: Despite improved mitral repair techniques, some children need mitral
      valve replacement (MVR). Due to small annulus size, supra-annular MVR is useful.
      METHODS: From 2003 to 2010, 15 children had 23 supra-annular MVRs. At first supra
      annular MVR, median age was 6.5 months (28 days to 47 months); median weight was
      5.4 kg (3.3-11.8 kg). Twelve (80%) had prior operations, 8 (53%) had previous
      mitral repair. Eight had congenital mitral anomalies (4 with Shone's), 5 had
      atrioventricular septal defects, 1 had endocarditis, and 1 had a repaired
      anomalous left coronary artery. All primary MVRs used mechanical valves (<= 17 mm
      in 9 patients). RESULTS: There was one early death (93% survival) in an 11-month
      old with congenital pulmonary vein stenosis. One intraoperative conversion from
      annular to supra-annular MVR developed heart block. Three pacemakers were
      implanted for supraventricular rhythm disturbances. Three children had valve
      thrombosis early postoperatively treated medically. On follow-up of 4.3 +/- 2.8
      years, 8 had reoperation including redo MVR in 6 for pannus formation or thrombus
      (1 had three redo MVRs). At redo, a larger valve was used in 5 and a
      bioprosthetic valve in 4 patients. There was one late death after third redo MVR
      with pulmonary vein stenosis relief (overall survival 87%). CONCLUSIONS: Supra
      annular MVR is useful for children with a small annulus. Operative survival is
      good with infrequent heart block. Complications are common, including redo MVR
      and need for left ventricular outflow tract obstruction relief. Pulmonary vein
      stenosis is a marker for poor outcome; all patients without pulmonary vein
      stenosis survive long term.

PMID- 21962267
TI  - A growing problem: maternal death and peripartum complications are higher in
      women with grown-up congenital heart disease.
AB  - BACKGROUND: As patients with grown-up congenital heart disease (GUCH) increase,
      more women with GUCH will become pregnant. Heart surgeons may be involved in
      maternal GUCH care, yet the prevalence, characteristics, and outcomes for these
      women are unknown. We determined the national prevalence of GUCH parturients,
      their diagnostic makeup, and whether they have increased risk of peripartum
      complications, maternal or fetal death. METHODS: We searched the Nationwide
      Inpatient Sample for women undergoing delivery in the United States between 1998
      and 2007, with GUCH patients indicated by a code for "congenital cardiac
      diagnosis complicating pregnancy," Patient and hospital characteristics were
      compared between women with and without GUCH. National estimates for maternal and
      fetal mortality, cardiac complications, induction, caesarean or surgically
      assisted birth, and preterm delivery were derived. Outcomes were compared between
      women with and without GUCH, and also within diagnostic GUCH subgroups. RESULTS:
      A total of 39.9 million births occurred, 26,973 (0.07%) of which were GUCH. Mean
      age was 27 years for both groups. Most common congenital diagnoses included
      ventricular septal defect (VSD) in 15%, aortic stenosis or insufficiency in 13%,
      atrial septal defect in 13%, pulmonary stenosis in 4%, and tetralogy of Fallot in
      2%. Stillborn delivery was equivalent among groups. Maternal mortality was 18
      fold higher in GUCH parturients (0.09%) compared with women without GUCH (0.005%;
      p < 0.001). Complications were higher for GUCH parturients compared with age
      matched women, including cardiac complications (2.3% vs 0.2%), induction (37% vs
      33%), caesarean or surgically assisted birth (45% vs 35%), and preterm delivery
      (10% vs 7%), p < 0.001 for all. A diagnosis of VSD was associated with the
      highest risk of maternal death and complications (p < 0.05 for all). More GUCH
      women delivered at teaching hospitals (58%) compared with women without GUCH
      (45%; p < 0.001). CONCLUSIONS: The GUCH parturients, especially those with VSD,
      have increased risk of mortality and peripartum complications compared with other
      age-matched women. Despite these risks, nearly 50% of GUCH patients deliver at
      nonteaching hospitals. Current national practice patterns for GUCH women are
      inadequate, and outcomes could be improved by education and proper triage of even
      relatively "simple" GUCH lesions such as atrial septal defect and VSD. Further
      studies that investigate risk-adjusted outcomes in a variety of care settings are
      necessary to resolve this complex issue.

PMID- 21962268
TI  - Survival after lobectomy versus segmentectomy for stage I non-small cell lung
      cancer: a population-based analysis.
AB  - BACKGROUND: Data comparing survival after lobectomy versus that after
      segmentectomy for stage I non-small cell lung cancer (NSCLC) are limited to
      single-institution observational studies and 1 clinical trial. We sought to
      determine if lobectomy offers a survival advantage over segmentectomy for stage I
      NSCLC based on population-based data. METHODS: Using the Surveillance
      Epidemiology and End Results (SEER) database (1998 to 2007), we identified
      patients who underwent either anatomic segmentectomy or lobectomy. Wedge
      resections were excluded. Analysis was limited to patients with stage I
      adenocarcinoma or squamous cell carcinoma. After stratifying patients based on
      tumor size (less than or equal to 2.0 cm, 2.1 to 3.0 cm, and 3.1 to 7.0 cm), we
      assessed for association between extent of resection and survival using the
      Kaplan-Meier method. To adjust for potential confounding variables, we used Cox
      proportional hazards regression models. RESULTS: There were 14,473 patients who
      met our inclusion criteria. Lobectomy conferred superior unadjusted overall (p <
      0.0001) and cancer-specific (p = 0.0053) 5-year survival compared with
      segmentectomy. Even after adjusting for patient factors, tumor characteristics,
      and geographic location, we noted that patients who underwent lobectomy had
      superior overall and cancer-specific survival rates, regardless of tumor size.
      Squamous cell histologic type, male sex, low lymph node counts, and increasing
      age, tumor size, and grade were all independent negative prognostic factors.
      CONCLUSIONS: Using a population-based data set, we found that lobectomy confers a
      significant survival advantage compared with segmentectomy. Our results provide
      additional evidence supporting the role of lobectomy as the standard of care for
      resection of stage I NSCLC regardless of tumor size.

PMID- 21962269
TI  - Drugs of abuse in oral fluid collected by two different sample kits--stability
      testing and validation using ultra performance tandem mass spectrometry analysis.
AB  - Oral fluid (OF) is an alternative matrix for monitoring drugs of abuse in
      workplace, clinical toxicology, criminal justice, and driving under the influence
      of drugs (DUID). OF is suitable for detection of drugs that have been taken
      recently. It is unproblematic to observe the collection and hence avoid the
      possibility of the samples being tampered. OF often contains compounds in low
      concentrations, and small volumes are often collected. It is therefore necessary
      to have a sensitive, multi component method for drug detection. In this study an
      ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS)
      method has been developed. The samples were prepared by liquid-liquid extraction
      (LLE) with ethyl acetate/heptane (4:1) and the separation was achieved by an
      Acquity HSS T3-column (2.1 mm * 100 mm, 1.8 MUm particles). Mass detection was
      performed by positive ion mode electrospray MS-MS. 32 drugs of abuse were
      determined with a cycle time of 9 min. Stability of drugs in oral fluid before
      analysis is an important factor that must be evaluated for each sampling device.
      The collection devices Intercept((r)) and StatSure Saliva SamplerTM were tested
      using pools of real samples containing various drugs. The testing showed that 6
      MAM (6-acetylmorphine), cocaine and zopiclone were the least stable compounds. In
      the testing for short term stability, StatSure Saliva SamplerTM showed better
      results. The testing of 1 year of storage at -20 degrees C showed that most of
      the compounds were stable for both sampling devices, except for 6-MAM, cocaine
      and zopiclone. Samples of OF should be analysed as soon as possible after
      collection, and they should be kept frozen if immediate analysis is not possible.

PMID- 21962271
TI  - Comparison of use of an infrared anesthetic gas monitor and refractometry for
      measurement of anesthetic agent concentrations.
AB  - OBJECTIVE: To assess agreement between anesthetic agent concentrations measured
      by use of an infrared anesthetic gas monitor (IAGM) and refractometry. SAMPLE-4
      IAGMs of the same type and 1 refractometer. PROCEDURES: Mixtures of oxygen and
      isoflurane, sevoflurane, desflurane, or N(2)O were used. Agent volume percent was
      measured simultaneously with 4 IAGMs and a refractometer at the common gas
      outlet. Measurements obtained with each of the 4 IAGMs were compared with the
      corresponding refractometer measurements via the Bland-Altman method. Similarly,
      Bland-Altman plots were also created with either IAGM or refractometer
      measurements and desflurane vaporizer dial settings. RESULTS: Bias +/- 2 SD for
      comparisons of IAGM and refractometer measurements was as follows: isoflurane, 
      0.03 +/- 0.18 volume percent; sevoflurane, -0.19 +/- 0.23 volume percent;
      desflurane, 0.43 +/- 1.22 volume percent; and N(2)O, -0.21 +/- 1.88 volume
      percent. Bland-Altman plots comparing IAGM and refractometer measurements
      revealed nonlinear relationships for sevoflurane, desflurane, and N(2)O.
      Desflurane measurements were notably affected; bias +/- limits of agreement (2
      SD) were small (0.1 +/- 0.22 volume percent) at < 12 volume percent, but both
      bias and limits of agreement increased at higher concentrations. Because IAGM
      measurements did not but refractometer measurements did agree with the desflurane
      vaporizer dial settings, infrared measurement technology was a suspected cause of
      the nonlinear relationships. CONCLUSIONS AND CLINICAL RELEVANCE: Given that the
      assumption of linearity is a cornerstone of anesthetic monitor calibration, this
      assumption should be confirmed before anesthetic monitors are used in
      experiments.

PMID- 21962272
TI  - Pharmacokinetics and physiologic effects of intramuscularly administered xylazine
      hydrochloride-ketamine hydrochloride-butorphanol tartrate alone or in combination
      with orally administered sodium salicylate on biomarkers of pain in Holstein
      calves following castration and dehorning.
AB  - OBJECTIVE: To determine the pharmacokinetic parameters of xylazine, ketamine, and
      butorphanol (XKB) administered IM and sodium salicylate (SAL) administered PO to
      calves and to compare drug effects on biomarkers of pain and distress following
      sham and actual castration and dehorning. ANIMALS: 40 Holstein bull calves from 3
      farms. PROCEDURES: Calves weighing 108 to 235 kg (n = 10 calves/group) received
      one of the following treatments prior to sham (period 1) and actual (period 2)
      castration and dehorning: saline (0.9% NaCl) solution IM (placebo); SAL
      administered PO through drinking water at concentrations from 2.5 to 5 mg/mL from
      24 hours prior to period 1 to 48 hours after period 2; butorphanol (0.025 mg/kg),
      xylazine (0.05 mg/kg), and ketamine (0.1 mg/kg) coadministered IM immediately
      prior to both periods; and a combination of SAL and XKB (SAL+XKB). Plasma drug
      concentrations, average daily gain (ADG), chute exit velocity, serum cortisol
      concentrations, and electrodermal activity were evaluated. RESULTS: ADG (days 0
      to 13) was significantly greater in the SAL and SAL+XKB groups than in the other
      2 groups. Calves receiving XKB had reduced chute exit velocity in both periods.
      Serum cortisol concentrations increased in all groups from period 1 to period 2.
      However, XKB attenuated the cortisol response for the first hour after castration
      and dehorning and oral SAL administration reduced the response from 1 to 6 hours.
      Administration of XKB decreased electrodermal activity scores in both periods.
      CONCLUSIONS AND CLINICAL RELEVANCE: SAL administered PO through drinking water
      decreased cortisol concentrations and reduced the decrease in ADG associated with
      castration and dehorning in calves.

PMID- 21962273
TI  - Cartilage thickness of the trochlea of the talus, with emphasis on sites
      predisposed to osteochondrosis dissecans, in clinically normal juvenile and adult
      dogs.
AB  - OBJECTIVE: To evaluate cartilage thickness of the talus (especially at sites
      predisposed to osteochondrosis dissecans [OCD]) in growing and adult dogs not
      affected with OCD. SAMPLE: Tarsocrural joints from cadavers of 34 juvenile
      (approx 3 months old) and 10 adult dogs. PROCEDURES: Tarsal cartilage thickness
      was examined via a stereophotography microscopic system. Articular cartilage
      thickness was determined at 11 locations on longitudinal slices of the trochlear
      ridges and the sulcus between the ridges and at 2 locations in the cochlea
      tibiae. Cartilage thickness was measured at the proximal, proximodorsal, dorsal,
      and distal aspects of the trochlear ridges; proximodorsal, dorsal, and distal
      aspects of the trochlear sulcus; and craniolateral and caudomedial aspects of the
      cochlea tibiae. Differences within a joint and between sexes were evaluated.
      RESULTS: Mean cartilage thickness decreased from proximal to distal in juvenile
      (lateral trochlear ridge, 1.52 to 0.41 mm; medial trochlear ridge, 1.10 to 0.40
      mm) and from proximal to dorsal in adult (lateral trochlear ridge, 0.41 to 0.34
      mm; medial trochlear ridge, 0.33 to 0.23 mm) dogs. Cartilage was thickest at the
      proximal aspect of the lateral trochlear ridge in both groups. Differences in
      proximodorsal, dorsal, and distal aspects of the ridges were not evident.
      CONCLUSIONS AND CLINICAL RELEVANCE: Healthy tarsocrural joints did not have
      thicker cartilage in sites predisposed to development of OCD. Evaluation of
      affected tarsocrural joints is necessary to exclude influences of cartilage
      thickness. These data are useful as a reference for distribution of cartilage
      thickness of the trochlea of the talus in dogs.

PMID- 21962274
TI  - Independent and combined effects of prednisone and acetylsalicylic acid on
      thromboelastography variables in healthy dogs.
AB  - OBJECTIVE: To describe the effects of prednisone and acetylsalicylic acid (ASA)
      on results of thromboelastography in healthy dogs. ANIMALS: 16 male mixed-breed
      dogs. PROCEDURES: Dogs were randomly assigned to 3 treatment groups (4
      dogs/group) that received prednisone (median dose, 2.07 mg/kg), ASA (median dose,
      0.51 mg/kg), or both drugs, PO, every 24 hours from days 0 through 6. Another
      group received no treatment (control dogs; n = 4). Thromboelastography variables
      (reaction time, clotting time, alpha-angle, maximum amplitude [MA], global clot
      strength, coagulation index, and percentage of clot lysis at 60 minutes [CL(60)])
      were evaluated in blood samples collected (prior to drug administration in
      treated dogs) on days 0 (baseline), 2, 4, and 6. RESULTS: Administration of ASA
      alone did not alter TEG variables. For treatment effect, mean global clot
      strength was increased in the prednisone and drug combination groups, compared
      with values for control dogs; MA was also increased in the prednisone and drug
      combination groups, compared with that of controls. For treatment-by-time effect,
      median CL(60) was increased in the prednisone group on day 6, compared with
      baseline value in the same dogs and with median CL(60) of the control group on
      day 6. Median CL(60) was also increased in the drug combination group on day 6,
      compared with the baseline value and with that of the control group on day 6.
      CONCLUSIONS AND CLINICAL RELEVANCE: Prednisone administered at approximately 2
      mg/kg/d, PO, for 7 days with or without concurrently administered ASA increased
      clot strength and decreased clot lysis in healthy dogs.

PMID- 21962275
TI  - Evaluation of perinuclear antineutrophilic cytoplasmic antibodies in sera from
      dogs with inflammatory bowel disease or intestinal lymphoma.
AB  - OBJECTIVE: To assess and compare the expression of perinuclear antineutrophilic
      cytoplasmic antibodies (pANCA) in sera obtained from dogs with inflammatory bowel
      disease (IBD) and dogs with intestinal lymphoma. ANIMALS: 104 dogs with IBD and
      23 dogs with intestinal lymphoma. PROCEDURES: Each ill dog had persistent
      gastrointestinal signs (> 3 weeks in duration) and absence of response to diet
      changes or antimicrobial treatments. Gastrointestinal endoscopy was performed in
      ill dogs to obtain intestinal biopsy specimens for histologic confirmation of IBD
      or lymphoma. A serum sample was obtained from each ill dog. Neutrophils were
      isolated from a blood sample from the healthy dog; neutrophil-bearing slides were
      incubated with serum from each ill dog and examined for expression of pANCA by
      use of an indirect immunofluorescence technique. Detection of cells that had a
      perinuclear fluorescence pattern was considered a positive result. RESULTS: The 2
      groups of dogs did not differ with regard to breed and sex but did differ with
      regard to age. Expression of pANCA was detected in 38 of the 104 (36.5%) dogs
      with IBD and 4 of the 23 (17.4%) dogs with intestinal lymphoma. Although the
      frequency of pANCA expression was higher in dogs with IBD, compared with findings
      in dogs with intestinal lymphoma, the difference was not significant. CONCLUSIONS
      AND CLINICAL RELEVANCE: Results indicated that circulating pANCA are present in
      some dogs with IBD or intestinal lymphoma. However, pANCA detection does not seem
      to be useful for distinguishing dogs with IBD from dogs with intestinal lymphoma.

PMID- 21962276
TI  - Use of data collected at cessation of lactation to predict incidence of sole
      ulcers and white line disease during the subsequent lactation in dairy cows.
AB  - OBJECTIVE: To develop a parsimonious statistical model to predict incidence of
      lameness in the subsequent lactation by use of data collected at cessation of
      lactation in dairy cows. ANIMALS: 574 cows. PROCEDURES: At cessation of lactation
      during hoof trimming, body condition score (BCS), visual locomotion score,
      digital cushion thickness (DCT), and digital lesions were assessed. RESULTS: 140
      (24%) cows were treated for claw horn disruption lesions (CHDLs) at cessation of
      lactation (114 with sole ulcers [pododermatitis circumscripta] and 26 with white
      line disease). The BCS was highly associated with DCT. Cows with CHDLs at
      cessation of lactation had significantly lower DCT, compared with other cows. All
      3 logistic regression models predicted the incidence of CHDLs in the subsequent
      lactation with good accuracy; the area under the receiver operating
      characteristic curves was 0.76, 0.76, and 0.77 for the first, second, and third
      logistic regression models, respectively. CONCLUSION AND CLINICAL RELEVANCE:
      Evaluation of 3 logistic regression models indicated that lameness could be
      predicted with good accuracy by use of all 3. The ability to predict lameness
      will facilitate the implementation of lameness prevention strategies by targeting
      specific cows.

PMID- 21962277
TI  - Perfusion method for harvesting bone marrow cells from dogs.
AB  - OBJECTIVE: To compare composition and colony formation of bone marrow mononuclear
      cells (BMMCs) harvested from dogs by means of a new perfusion method and the
      conventional aspiration method. ANIMALS: 7 healthy adult Beagles. PROCEDURES:
      BMMCs were collected from the humeri and femurs of Beagles via perfusion and
      aspiration methods. Flow cytometric analysis was performed to quantify the
      presence of contaminant cells from the peripheral blood and the percentage of
      CD34+ progenitor cells in the BMMCs. A CFU assay was conducted to determine the
      number of progenitor cells in the BMMCs. RESULTS: The perfusion method was safely
      performed in all 7 dogs. Flow cytometric analysis revealed that the percentages
      of contaminant CD3+CD4+, CD3+CD8+, and CD21 + lymphocytes in BMMCs obtained via
      perfusion were significantly lower than percentages obtained via aspiration. The
      percentage of CD34+ cells obtained via perfusion was significantly higher than
      that obtained via aspiration. In addition, perfusion yielded a significantly
      higher CFU count than did aspiration. CONCLUSIONS AND CLINICAL RELEVANCE: The
      perfusion method used in this study can minimize the contamination of bone marrow
      samples with peripheral blood and was a more efficient means for collecting
      canine bone marrow progenitor cells than the conventional aspiration method.
      Therefore, the perfusion method can be more suitable than aspiration for
      harvesting bone marrow cells for transplantation in dogs.

PMID- 21962278
TI  - Effectiveness of sorting calves with high risk of developing bovine respiratory
      disease on the basis of serum haptoglobin concentration at the time of arrival at
      a feedlot.
AB  - OBJECTIVE: To evaluate serum haptoglobin concentration at feedlot arrival and
      subsequent performance and morbidity and mortality rates of calves that developed
      bovine respiratory disease. ANIMALS: 360 heifer calves and 416 steer and bull
      calves. PROCEDURES: Serum samples were obtained from cattle at the time of
      arrival to a feedlot (day -1) and analyzed for haptoglobin concentration. In
      experiment 1, calves were classified into groups with a low (< 1.0 MUg/mL),
      medium (1.0 to 3.0 MUg/mL), or high (> 3.0 MUg/mL) serum haptoglobin
      concentration and allotted into pens on the basis of group. In experiment 2,
      calves were classified as having or not having detectable serum haptoglobin
      concentrations. RESULTS: In experiment 1, average daily gain from days 1 to 7
      decreased as haptoglobin concentration increased. Dry-matter intake (DMI) from
      days 1 to 21 decreased with increasing haptoglobin concentration, and DMI
      typically decreased from days 1 to 63. Total bovine respiratory disease morbidity
      rate typically increased with increasing haptoglobin concentration. At harvest,
      no differences in carcass characteristics were observed on the basis of
      haptoglobin concentration. In experiment 2, cattle with measureable serum
      haptoglobin concentrations at arrival weighed less throughout the experiment,
      gained less from days 1 to 7, and had lower DMI from days 1 to 42. Overall
      morbidity rate was not different between groups, but cattle with detectable serum
      haptoglobin concentrations had higher odds of being treated 3 times. CONCLUSIONS
      AND CLINICAL RELEVANCE: Serum haptoglobin concentration in cattle at the time of
      feedlot arrival was not associated with overall performance but may have limited
      merit for making decisions regarding targeted prophylactic treatment.

PMID- 21962279
TI  - Enterotoxin production, enterotoxin gene distribution, and genetic diversity of
      Staphylococcus aureus recovered from milk of cows with subclinical mastitis.
AB  - OBJECTIVE: To evaluate enterotoxin production, enterotoxin gene distribution, and
      genetic diversity of Staphylococcus aureus in milk obtained from cows with
      subclinical mastitis. SAMPLE: Milk samples obtained from 350 cows (1,354 mammary
      glands) on 11 Wisconsin dairy farms. PROCEDURES: Of 252 S aureus isolates
      obtained from 146 cows, 83 isolates (from 66 cows with subclinical mastitis) were
      compared genotypically by use of pulsed-field gel electrophoresis and via PCR
      identification of toxic shock syndrome toxin 1 (TSST-1) and classical S aureus
      enterotoxin genes (sea, seb, sec, sed, and see). RESULTS: Among the 83 S aureus
      isolates, >= 1 enterotoxin genes were identified in 8 (9.6%). Enterotoxin gene
      distribution was as follows: TSST-1, 7 isolates (8.4%); sec, 5 isolates (6.0%);
      and sed, 2 isolates (2.4%). Enterotoxin genes sea, seb, and see were not
      identified. Twelve pulsotypes and 5 subtypes were identified among the 83
      isolates; 5 of the 12 pulsotypes were represented by only 1 isolate. In cows of 1
      herd, only a single S aureus pulsotype was detected; in cows on most other farms,
      a variety of pulsotypes were identified. One pulsotype was recovered from 4 farms
      (n = 23 cows) and another from 5 other farms (16). Isolates with an enterotoxin
      gene were represented by 6 pulsotypes. CONCLUSIONS AND CLINICAL RELEVANCE: S
      aureus classical enterotoxins and TSST-1 were rarely recovered from milk samples
      obtained from cows with subclinical mastitis in Wisconsin. Diverse pulsotypes of
      S aureus were detected within and among farms, indicating that different strains
      of S aureus cause subclinical mastitis in dairy cows.

PMID- 21962280
TI  - 5-lipoxygenase expression and tepoxalin-induced cell death in squamous cell
      carcinomas in cats.
AB  - OBJECTIVE: To assess expression pattern and subcellular compartmentalization of 5
      lipoxygenase in cutaneous, UV radiation-induced, and oral squamous cell
      carcinomas (SCCs) in cats and determine the effects of cyclooxygenase or 5
      lipoxygenase inhibition on proliferation or apoptosis in a feline oral squamous
      cell carcinoma (SCCF1) cell line. SAMPLE: 60 archived paraffin-embedded samples
      of SCCs from 60 cats and SCCF1 cells. PROCEDURES: Retrospective
      immunohistochemical analysis of the archived samples of SCCs (20 cutaneous, 20 UV
      radiation-induced, and 20 oral tumors) was performed. Cell culture proliferation
      assays involving SCCF1 cells were performed, and tepoxalin-induced apoptosis and
      signaling were examined via western blotting and annexin V staining. RESULTS:
      Immunohistochemically, staining for 5-lipoxygenase was most frequently of
      greatest intensity in oral SCCs, whereas staining of cutaneous and UV radiation
      induced lesions had less consistent 5-lipoxygenase expression. Exposure of SCCF1
      cells to the 5-lipoxygenase inhibitor tepoxalin resulted in apoptosis; the effect
      appeared to be mediated via alteration of cell signaling rather than via
      suppression of lipid mediators that are typically produced as a result of 5
      lipoxygenase activity. CONCLUSIONS AND CLINICAL RELEVANCE: In cats, expression of
      5-lipoxygenase in SCCs appeared to differ depending on tumor location. The
      influence of tepoxalin-induced 5-lipoxygenase inhibition on a 5-lipoxygenase
      expressing cell line coupled with the notable expression of 5-lipoxygenase in
      oral SCCs suggested that 5-lipoxygenase inhibition may have therapeutic benefits
      in affected cats. Although the safety of tepoxalin in cats has yet to be
      investigated, 5-lipoxygenase inhibitors should be evaluated for use as a
      potential treatment for SCCs in that species.

PMID- 21962281
TI  - Pharmacokinetics and pharmacodynamics of detomidine following sublingual
      administration to horses.
AB  - OBJECTIVE: To characterize pharmacokinetics and pharmacodynamics of detomidine
      gel administered sublingually in accordance with label instructions to establish
      appropriate withdrawal guidelines for horses before competition. ANIMALS: 12
      adult racehorses. PROCEDURES: Horses received a single sublingual administration
      of 0.04 mg of detomidine/kg. Blood samples were collected before and up to 72
      hours after drug administration. Urine samples were collected for 5 days after
      detomidine administration. Plasma and urine samples were analyzed via liquid
      chromatography-mass spectrometry, and resulting data were analyzed by use of
      noncompartmental analysis. Chin-to-ground distance, heart rate and rhythm,
      glucose concentration, PCV, and plasma protein concentration were also assessed
      following detomidine administration. RESULTS: Mean +/- SD terminal elimination
      half-life of detomidine was 1.5 +/- 1 hours. Metabolite concentrations were below
      the limit of detection (0.02, 0.1, and 0.5 ng/mL for detomidine,
      carboxydetomidine, and hydroxydetomidine, respectively) in plasma by 24 hours.
      Concentrations of detomidine and its metabolites were below the limit of
      detection (0.05 ng/mL for detomidine and 0.10 ng/mL for carboxydetomidine and
      hydroxydetomidine) in urine by 3 days. All horses had various degrees of sedation
      after detomidine administration. Time of onset was <= 40 minutes, and duration of
      sedation was approximately 2 hours. Significant decreases, relative to values at
      time 0, were detected for chin-to-ground distance and heart rate. There was an
      increased incidence and exacerbation of preexisting atrioventricular blocks after
      detomidine administration. CONCLUSIONS AND CLINICAL RELEVANCE: A 48-hour and 3
      day withdrawal period for detection in plasma and urine samples, respectively,
      should be adopted for sublingual administration of detomidine gel.

PMID- 21962282
TI  - Pharmacokinetics of ponazuril after oral administration to healthy llamas (Lama
      glama).
AB  - OBJECTIVE: To determine the pharmacokinetics after oral administration of a
      single dose of ponazuril to healthy llamas. ANIMALS: 6 healthy adult llamas.
      PROCEDURES: Ponazuril (20 mg/kg) was administered once orally to 6 llamas (day
      0). Blood samples were obtained on days 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 11, 14,
      21, 28, 35, 42, and 49. Serum ponazuril concentrations were determined by use of
      a validated reverse-phase high-performance liquid chromatography assay with UV
      absorbance detection. Pharmacokinetic parameters were derived by use of a
      standard noncompartmental pharmacokinetic analysis. RESULTS: Mean +/- SD area
      under the serum concentration-time curve was 7,516 +/- 2,750 h*mg/L, maximum
      serum ponazuril concentration was 23.6 +/- 6.0 mg/L, and the elimination half
      life was 135.5 +/- 16.7 hours. Serum concentration of ponazuril peaked at 84
      hours (range, 48 to 120 hours) after administration and gradually decreased but
      remained detectable for up to 35 days after administration. No adverse effects
      were observed during the study period. CONCLUSIONS AND CLINICAL RELEVANCE: The
      rate and extent of absorption following oral administration of a single dose of
      ponazuril were sufficient to result in potentially effective concentrations, and
      the drug was tolerated well by llamas. At this dose, ponazuril resulted in serum
      concentrations that were high enough to be effective against various
      Apicomplexans on the basis of data for other species. The effective ponazuril
      concentration that will induce 50% inhibition of parasite growth for Eimeria
      macusaniensis in camelids is currently unknown.

PMID- 21962283
TI  - Determination of body water compartments in neonatal foals by use of indicator
      dilution techniques and multifrequency bioelectrical impedance analysis.
AB  - OBJECTIVE: To determine values for total body water (TBW), extracellular fluid
      volume (ECFV), intracellular fluid volume (ICFV), and plasma volume (PV) in
      healthy neonatal (< 24 hours old) foals and to create a multifrequency
      bioelectrical impedance analysis (MF-BIA) model for use in neonatal foals.
      ANIMALS: 7 healthy neonatal foals. PROCEDURES: Deuterium oxide (0.4 g/kg, IV),
      sodium bromide (30 mg/kg, IV), and Evans blue dye (1 mg/kg, IV) were administered
      to each foal. Plasma samples were obtained following an equilibration period, and
      the TBW, ECFV, ICFV, and PV were calculated for each foal. An MF-BIA model was
      created by use of morphometric measurements from each foal. RESULTS: Mean +/- SD
      values were obtained for TBW (0.744 +/- 0.024 L/kg), ICFV (0.381 +/- 0.018 L/kg),
      ECFV (0.363 +/- 0.014 L/kg), and PV (0.096 +/- 0.015 L/kg). The 95% limits of
      agreement between the MF-BIA and indicator dilution techniques were within +/- 2
      L for TBW and ECFV. CONCLUSIONS AND CLINICAL RELEVANCE: Fluid volumes in neonatal
      foals were found to be substantially larger than fluid volumes in adult horses.
      Multifrequency bioelectrical impedance analysis may be a useful technique for
      predicting TBW, ICFV, and ECFV in neonatal foals.

PMID- 21962284
TI  - Evaluation of the histologic reactions to commonly used suture materials in the
      skin and musculature of ball pythons (Python regius).
AB  - OBJECTIVE: To evaluate histologic reactions to 8 suture materials and
      cyanoacrylate tissue adhesive (CTA) in the musculature and skin of ball pythons.
      ANIMALS: 30 hatchling ball pythons. PROCEDURES: In each snake, ten 1-cm skin
      incisions were made (day 0). At 8 sites, a suture of 1 of 8 materials was placed
      in the epaxial musculature, and the incision was closed with the same material.
      One incision was closed by use of CTA. No suture material was placed in the tenth
      incision, which was allowed to heal by second intention (negative control).
      Snakes (n = 5/group) were euthanized for harvest of treatment-site tissues at
      days 3, 7, 14, 30, 60, and 90. Skin and muscle sections were examined
      microscopically and assigned a subjective score (0 to 4) for each of the
      following: overall severity of inflammation, fibrosis, number of macrophages,
      number of granulocytes, number of perivascular lymphocytes, and degree of suture
      fragmentation. RESULTS: Subjective score analysis revealed that CTA did not cause
      a significant inflammatory response, compared with the negative control. All
      suture materials caused significantly more inflammation over all time points; for
      all suture materials, inflammatory response scores were significantly higher than
      values for the negative control 90 days after implantation. No sutures were
      completely absorbed by the end of the study period, and several sutures appeared
      to be in the process of extrusion. CONCLUSIONS AND CLINICAL RELEVANCE: In snakes,
      CTA can be used to close small superficial incisions or lacerations with minimal
      inflammatory response, and sutures may undergo extrusion from tissues prior to
      complete absorption.

PMID- 21962285
TI  - Comparison of urine protein profiles in cats without urinary tract disease and
      cats with idiopathic cystitis, bacterial urinary tract infection, or
      urolithiasis.
AB  - OBJECTIVE: To characterize and compare the urine protein content in cats without
      urinary tract disease and cats with idiopathic cystitis (IdC), bacterial urinary
      tract infection (UTI), or urolithiasis. ANIMALS: Control cats (n = 18) and cats
      with IdC (18), UTI (12), and urolithiasis (12) from which urine samples were
      obtained and 2 cats with obstructive IdC and 4 additional control cats from which
      postmortem urinary bladder biopsy specimens were obtained. PROCEDURES: Protein
      contents in urine samples obtained via cystocentesis or catheterization were
      measured via the Bradford method. Urine proteins were separated by means of 1
      dimensional gel electrophoresis. Evaluation of fibronectin content was performed
      via western blotting and immunohistochemical analysis. Urinary bladder biopsy
      specimens were examined histologically and analyzed immunohistochemically for
      fibronectin. RESULTS: Urine fibronectin content was significantly greater in cats
      with IdC, compared with control cat findings. Urine fibronectin contents did not
      differ significantly among controls and cats with UTI or urolithiasis. Histologic
      examination of bladder biopsy specimens obtained from 2 cats with obstructive IdC
      revealed destruction of the urothelial lining of the urinary bladder and severe
      fibrosis; immunohistochemical analysis revealed few fluorescence signals for
      fibronectin, unlike findings in control bladder biopsy specimens. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results indicated that urine fibronectin content in cats with
      IdC was greater than that in controls, cats with UTI, or cats with urolithiasis.
      In cats with IdC, increased permeability of damaged urothelium may result in
      detachment and leakage of fibronectin into urine. Urine fibronectin might serve
      as a biomarker for diagnosis of IdC in cats.

PMID- 21962286
TI  - Vocal symptoms in women undergoing in vitro fertilization.
AB  - OBJECTIVE: The aim of this study was to investigate changes in vocal symptoms in
      relation to estrogen level in women undergoing in vitro fertilization. MATERIALS
      AND METHODS: A total of 31 women were enrolled in this study. The following vocal
      symptoms were investigated: vocal tiring or fatigue, vocal straining, throat
      clearing, lump sensation, hoarseness, and aphonia (or loss of voice). The
      severity of these symptoms was graded from 0 to 4, where 0 means absence of the
      symptom and 3 means severe symptom presence. The frequency of these symptoms was
      evaluated in the first visit at presentation; second visit, 4 to 5 days after
      ovarian stimulation; and third visit, 8 to 10 days after stimulation. In the
      second and third visits, the estradiol levels were measured. RESULTS: The mean
      age was 32.33 +/- 4.80 years. Ten of the 31 patients had at least 1 vocal
      symptom. The most common vocal symptom in all 3 visits was throat clearing, with
      an incidence of 22.6% in the first and second visits and 19.4% in the third
      visit. This was followed by vocal fatigue or tiring and lump sensation, with an
      incidence of 9.68% for both. The incidence of all the vocal symptoms as well as
      their severity did not change throughout the visits, except for throat clearing,
      which has decreased in the third visit but not significantly (22.6% vs 19.4%, P =
      1). Subjects with vocal symptoms had lower estradiol level compared with those
      with no vocal symptoms; however, the difference was not statistically significant
      (P = .108 and .267, respectively). CONCLUSION: Subjects undergoing in vitro
      fertilization do not experience changes in their vocal symptoms when present,
      except for throat clearing. However, those with vocal symptoms have lower levels
      of estradiol compared with those with no vocal symptoms.

PMID- 21962287
TI  - Mucoepidermoid carcinoma of the parotid infiltrating the chorda tympani nerve.
AB  - We present here the first case report of a mucoepidermoid carcinoma of the
      parotid infiltrating the chorda tympani nerve and also discuss why an initial
      diagnosis of Bell palsy may be misleading.

PMID- 21962288
TI  - Arytenoid adduction combined with medialization laryngoplasty under general
      anesthesia using a laryngeal mask airway.
AB  - PURPOSE: Laryngeal framework surgery is usually performed under local anesthesia
      but cannot be tolerated by some patients. To develop a new procedure for these
      patients, we evaluated voice outcomes after arytenoid adduction combined with
      medialization laryngoplasty under general anesthesia using a laryngeal mask
      airway (LMA) for unilateral vocal cord paralysis. MATERIALS AND METHODS: Eleven
      consecutive patients with severe unilateral vocal cord paralysis, with a maximum
      phonation time of less than 5 seconds, underwent arytenoid adduction combined
      with medialization laryngoplasty under general anesthesia using an LMA. Each
      paralyzed vocal cord was observed by intraoperative videolaryngoscopy. The vocal
      cord was moved to the position where the best vocal outcome could be expected,
      according to 3 parameters obtained from glottal images. RESULTS: All patients
      achieved a maximum phonation time of more than 11 seconds. The mean airflow rate,
      which ranged from 550 to 1000 mL/s before surgery, improved to less than 390
      mL/s. Perceptual evaluation using the grade, roughness, breathiness, asthenia and
      strain scale also improved significantly. CONCLUSIONS: These results were
      equivalent to those of previous reports of surgeries performed under local
      anesthesia. Intraoperative endoscopic vocal cord observation through the LMA may
      have contributed to the positive results.

PMID- 21962289
TI  - Brainstem hemorrhage presented as audiovestibular syndromes.
AB  - Brainstem hemorrhage usually presented with acute multiple neurologic
      dysfunction, and the prognosis was poor. Rarely, it can manifest with
      audiovestibular symptoms only. Here, we report a case of brainstem hemorrhage
      involving the right middle cerebellar peduncle and dorsal lateral pons presented
      with constant nonpulsatile tinnitus and rotatory vertigo. We believed that
      rotatory nystagmus should be regarded as a central sign until proven otherwise
      even if the neurologic signs are subtle.

PMID- 21962290
TI  - The use of magnetic resonance imaging to predict ACL graft structural properties.
AB  - Magnetic resonance imaging (MRI) could potentially be used to non-invasively
      predict the strength of an ACL graft after ACL reconstruction. We hypothesized
      that the volume and T2 relaxation parameters of the ACL graft measured with MRI
      will predict the graft structural properties and anteroposterior (AP) laxity of
      the reconstructed knee. Nine goats underwent ACL reconstruction using a patellar
      tendon autograft augmented with a collagen or collagen-platelet composite. After
      6 weeks of healing, the animals were euthanized, and the reconstructed knees were
      retrieved and imaged on a 3T scanner. AP laxity was measured prior to dissecting
      out the femur-graft-tibia constructs which were then tested to tensile failure to
      determine the structural properties. Regression analysis indicated a
      statistically significant relationship between the graft volume and the failure
      load (r(2)=0.502; p=0.049). When graft volume was normalized to the T2 relaxation
      time, the relationship was even greater (r(2)=0.687; p=0.011). There was a
      significant correlation between the graft volume and the linear stiffness
      (r(2)=0.847; p<0.001), which remained significant with T2 normalization
      (r(2)=0.764; p=0.002). For AP laxity at 30 degrees  flexion, there was not a
      significant correlation with graft volume, but there was a significant
      correlation with volume normalized by the T2 relaxation time (r(2)=0.512;
      p=0.046). These results suggest that MRI volumetric measures combined with graft
      T2 properties may be useful in predicting the structural properties of ACL
      grafts.

PMID- 21962291
TI  - Pleiotropic signaling pathways orchestrate yeast development.
AB  - Developmental phenotypes in Saccharomyces cerevisiae and related yeasts include
      responses such as filamentous growth, sporulation, and the formation of biofilms
      and complex colonies. These developmental phenotypes are regulated by
      evolutionarily conserved, nutrient-responsive signaling networks. The signaling
      mechanisms that control development in yeast are highly pleiotropic--all the
      known pathways contribute to the regulation of multiple developmental outcomes.
      This degree of pleiotropy implies that perturbations of these signaling pathways,
      whether genetic, biochemical, or environmentally induced, can manifest in
      multiple (and sometimes unexpected) ways. We summarize the current state of
      knowledge of developmental pleiotropy in yeast and discuss its implications for
      understanding functional relationships.

PMID- 21962292
TI  - Efficacy of malaria prevention during pregnancy in an area of low and unstable
      transmission: an individually-randomised placebo-controlled trial using
      intermittent preventive treatment and insecticide-treated nets in the Kabale
      Highlands, southwestern Uganda.
AB  - Intermittent preventive treatment of malaria during pregnancy (IPTp) and
      insecticide-treated nets (ITN) are recommended malaria interventions during
      pregnancy; however, there is limited information on their efficacy in areas of
      low malaria transmission in sub-Saharan Africa. An individually-randomised
      placebo-controlled trial involving 5775 women of all parities examined the effect
      of IPTp, ITNs alone, or ITNs used in combination with IPTp on maternal anaemia
      and low birth weight (LBW) in a highland area of southwestern Uganda. The overall
      prevalence of malaria infection, maternal anaemia and LBW was 15.0%, 14.7% and
      6.5%, respectively. Maternal and fetal outcomes were generally remarkably similar
      across all intervention groups (P>0.05 for all outcomes examined). A marginal
      difference in maternal haemoglobin was observed in the dual intervention group
      (12.57g/dl) compared with the IPTp and ITN alone groups (12.40g/dl and 12.44g/dl,
      respectively; P=0.04), but this was too slight to be of clinical importance. In
      conclusion, none of the preventive strategies was found to be superior to the
      others, and no substantial additional benefit to providing both IPTp and ITNs
      during routine antenatal services was observed. With ITNs offering a number of
      advantages over IPTp, yet showing comparable efficacy, we discuss why ITNs could
      be an appropriate preventive strategy for malaria control during pregnancy in
      areas of low and unstable transmission.

PMID- 21962293
TI  - Unnecessary antibiotic use for mild acute respiratory infections during 28-day
      follow-up of 823 children under five in rural Vietnam.
AB  - Few prospective studies regarding antibiotic use for mild acute respiratory
      infections (ARI) have been conducted in community settings. This paper aimed to
      assess knowledge of children's caregivers and actual antibiotic use for children
      under five and to identify factors associated with antibiotic treatment for mild
      ARIs. Caregivers in 828 households in Bavi, Vietnam, were interviewed using a
      structured questionnaire assessing both knowledge and practice. Subsequently, 823
      children were followed for 28 days to collect information regarding symptoms and
      drug use. For management of ARIs, only 13% of caregivers demonstrated correct
      overall knowledge in accordance with standard guidelines. The symptoms of the
      most recent illness were consistent with mild ARI in 79% of cases, and
      antibiotics were used in 71% of these. During the 28-day period, 62% of children
      had been given antibiotics and 63% of antibiotic courses were used for mild ARIs.
      One-half of the mild ARI episodes and 63% of the children with mild ARIs were
      treated with antibiotics. Most of the unnecessary antibiotic treatment was
      recommended by healthcare providers (82%). Most of the children had been
      administered antibiotics for common colds, although most caregivers believed that
      antibiotics were not required. Antibiotics were unnecessarily recommended at
      health facilities in the area.

PMID- 21962294
TI  - Combining stem cells and genes for effective therapeutics.

PMID- 21962295
TI  - Nonenzymatic assembly of natural polyubiquitin chains of any linkage composition
      and isotopic labeling scheme.
AB  - Polymeric chains made of a small protein ubiquitin act as molecular signals
      regulating a variety of cellular processes controlling essentially all aspects of
      eukaryotic biology. Uncovering the mechanisms that allow differently linked
      polyubiquitin chains to serve as distinct molecular signals requires the ability
      to make these chains with the native connectivity, defined length, linkage
      composition, and in sufficient quantities. This, however, has been a major
      impediment in the ubiquitin field. Here, we present a robust, efficient, and
      widely accessible method for controlled iterative nonenzymatic assembly of
      polyubiquitin chains using recombinant ubiquitin monomers as the primary building
      blocks. This method uses silver-mediated condensation reaction between the C
      terminal thioester of one ubiquitin and the epsilon-amine of a specific lysine on
      the other ubiquitin. We augment the nonenzymatic approaches developed recently by
      using removable orthogonal amine-protecting groups, Alloc and Boc. The use of
      bacterially expressed ubiquitins allows cost-effective isotopic enrichment of any
      individual monomer in the chain. We demonstrate that our method yields completely
      natural polyubiquitin chains (free of mutations and linked through native
      isopeptide bonds) of essentially any desired length, linkage composition, and
      isotopic labeling scheme, and in milligram quantities. Specifically, we
      successfully made Lys11-linked di-, tri-, and tetra-ubiquitins, Lys33-linked
      diubiquitin, and a mixed-linkage Lys33,Lys11-linked triubiquitin. We also
      demonstrate the ability to obtain, by high-resolution NMR, residue-specific
      information on ubiquitin units at any desired position in such chains. This
      method opens up essentially endless possibilities for rigorous structural and
      functional studies of polyubiquitin signals.

PMID- 21962297
TI  - Injury to the infrapatellar branch of the saphenous nerve, a possible cause for
      anterior knee pain after tibial nailing?
AB  - The purpose of this study was to determine the long-term incidence of
      infrapatellar nerve damage after tibial nailing and its relation to anterior knee
      pain. We retrospectively evaluated 71 patients in whom 72 isolated tibial shaft
      fractures were treated with an intramedullary nail. The mean follow-up time was
      84 months. Twenty-seven patients (38%) complained of chronic anterior knee pain.
      Infrapatellar nerve damage was found in 43 patients (60%). Of the 27 patients
      with knee pain, 21 (78%) had sensory deficits in the distribution area of the
      infrapatellar nerve, compared to 22 of the 45 patients (49%) without knee pain
      (p=0.025). Patient and fracture characteristics showed no significant differences
      between the two groups. At time of follow-up a total of 33 nails were removed of
      which twelve were taken out because of knee pain. The pain persisted in seven of
      these twelve patients (58%). The incidence of iatrogenic damage to the
      infrapatellar nerve after tibial nailing is high and lasting. Injury to this
      nerve appears to be associated with anterior knee pain after tibial nailing.

PMID- 21962296
TI  - Rest easy? Is bed rest really necessary after surgical repair of an ankle
      fracture?
AB  - INTRODUCTION: Bed rest with elevation of the affected limb is commonly prescribed
      postoperatively following ankle fracture fixation although there is no evidence
      that this is necessary. AIM: The aim of this prospective, randomised study was to
      investigate the effects of early mobilisation following surgical fixation of an
      ankle fracture on wound healing and length of stay (LOS). METHOD: A total of 104
      patients underwent primary internal fixation of an ankle fracture at The Alfred
      hospital, Melbourne between July 2008 and January 2010. INTERVENTION: The
      strategy included either early mobilisation group (first day post surgery) or
      control group (bed rest with elevation until day 2 post surgery). OUTCOME
      MEASURES: Data collected included demographic, injury type and surgical
      procedure. Outcome data included inpatient LOS, wound condition at 10-14 days,
      opioid use and re-admission rate. RESULTS: Groups were comparable at baseline.
      Wound breakdown rate was 2.9% (3 patients in the control group). Median LOS of
      the early mobilisation group was 55 h compared with 71 h in the control group
      (p<0.0001). Opioid use for the control group was an average of 90 mg morphine
      equivalent in the first 24 h post surgery compared with 67 mg morphine equivalent
      for the early mobilisation group (p=0.32). CONCLUSION: This study indicates that
      early mobilisation following surgical fixation of an ankle fracture results in a
      shorter hospital stay without evidence of an increased risk of re-admission or
      wound complication.

PMID- 21962298
TI  - Benzothiazoles with tunable electron-withdrawing strength and reverse polarity: a
      route to triphenylamine-based chromophores with enhanced two-photon absorption.
AB  - A series of dipolar and octupolar triphenylamine-derived dyes containing a
      benzothiazole positioned in the matched or mismatched fashion have been designed
      and synthesized via palladium-catalyzed Sonogashira cross-coupling reactions.
      Linear and nonlinear optical properties of the designed molecules were tuned by
      an additional electron-withdrawing group (EWG) and by changing the relative
      positions of the donor and acceptor substituents on the heterocyclic ring. This
      allowed us to examine the effect of positional isomerism and extend the structure
      property relationships useful in the engineering of novel heteroaromatic-based
      systems with enhanced two-photon absorption (TPA). The TPA cross-sections
      (delta(TPA)) in the target compounds dramatically increased with the branching of
      the triphenylamine core and with the strength of the auxiliary acceptor. In
      addition, a change from the commonly used polarity in push-pull benzothiazoles to
      a reverse one has been revealed as a particularly useful strategy (regioisomeric
      control) for enhancing TPA cross-sections and shifting the absorption and
      emission maxima to longer wavelengths. The maximum TPA cross-sections of the star
      shaped three-branched triphenylamines are ~500-2300 GM in the near-infrared
      region (740-810 nm); thereby the molecular weight normalized delta(TPA)/MW values
      of the best performing dyes within the series (2.0-2.4 GM.g(-1).mol) are
      comparable to those of the most efficient TPA chromophores reported to date. The
      large TPA cross-sections combined with high emission quantum yields and large
      Stokes shifts make these compounds excellent candidates for various TPA
      applications, including two-photon fluorescence microscopy.

PMID- 21962299
TI  - Scholarly productivity, academic success, and beyond.

PMID- 21962300
TI  - Bench to bedside: dynamic mitral valve assessment.
AB  - PURPOSE: The authors analyze a commercially available software package capable of
      geometrically reconstructing the mitral valve (MV) dynamically throughout
      systole. DESCRIPTION: Three-dimensional echocardiography has revolutionized the
      understanding of MV geometry. Advanced quantification software can be used to
      assess geometric changes in the MV, which have been shown to have important
      implications for MV surgery. EVALUATION: The authors performed geometric analysis
      on 24 patients, with both anatomically normal and abnormal MVs to assess the
      feasibility of this new software. The application of this new software is briefly
      reviewed. CONCLUSION: This new software, despite its limitations, allows an
      improved perspective on MV geometry with implications for MV repair and surgical
      decision making.

PMID- 21962301
TI  - Case 5--2011: Acute respiratory distress syndrome in an infant after repair of
      tetralogy of Fallot.

PMID- 21962302
TI  - Pro: Early extubation following surgery for congenital heart disease.

PMID- 21962303
TI  - Con: Extubation in the operating room following pediatric cardiac surgery.

PMID- 21962304
TI  - Integrating outcome benefit into anesthetic design: the promise of steroids and
      statins.
AB  - Steroids and statins may facilitate the integration of anesthetic design with
      clinical outcome. Although steroids clearly benefit adult cardiac surgical
      patents, the evidence is weaker in pediatric cardiac surgery. Current large
      randomized trials of steroids likely will determine the future role of steroids
      in adult cardiac surgery. In the intensive care unit, steroid therapy is
      indicated in septic shock that is refractory to fluid and pressor therapy. Recent
      data, however, indicate that liberal steroid therapy for sepsis may have adverse
      outcome consequences. A 2nd concern in the intensive care unit is acute adrenal
      suppression secondary to bolus etomidate therapy because it may be deleterious in
      patients with septic shock. Possible clinical solutions include alternative
      induction agents, concomitant steroid therapy, and recent etomidate derivatives.
      Statins also reduce mortality and atrial fibrillation after cardiac surgery.
      Furthermore, they slow the progression of rheumatic valvular stenosis, an
      important consideration in the developing world. Statins also may reduce
      delirium, stroke, and acute renal injury after cardiac surgery, but further
      randomized trials are required before definitive recommendations can be
      formulated. Statins are essential in vascular surgery because they reduce
      mortality, myocardial ischemia, and acute renal injury. As a result, they have
      been recommended highly for outcome enhancement in recent perioperative
      guidelines. Although they may improve survival in sepsis, further investigation
      is indicated to define their therapeutic role.

PMID- 21962305
TI  - Hypoxia-reduced nitric oxide synthase activity is partially explained by higher
      arginase-2 activity and cellular redistribution in human umbilical vein
      endothelium.
AB  - Hypoxia relates with altered placental vasodilation, and in isolated endothelial
      cells, it reduces activity of the endothelial nitric oxide synthase (eNOS) and l
      arginine transport. It has been reported that arginase-2 expression, an
      alternative pathway for l-arginine metabolism, is increased in adult endothelial
      cells exposed to hypoxia as well as in pre-eclamptic placentae. We studied in
      human umbilical vein endothelial cells (HUVEC) whether hypoxia-reduced NO
      synthesis results from increased arginase-mediated l-arginine metabolism and
      changes in subcellular localization of eNOS and arginase-2. In HUVEC exposed (24
      h) to 5% (normoxia) or 2% (hypoxia) oxygen, l-arginine transport kinetics,
      arginase activity (urea assay), and NO synthase (NOS) activity (l-citrulline
      assay) were determined. Arginase-1, arginase-2 and eNOS expression were
      determined by RT-PCR and Western blot. Subcellular localization of arginase-2 and
      eNOS were studied using confocal microscopy and indirect immunofluorescence.
      Experiments were done in absence or presence of S-(2-boronoethyl)-l-cysteine-HCl
      (BEC, arginase inhibitor) or N(G)-nitro-l-arginine methyl ester (l-NAME). Hypoxia
      induced reduction in eNOS activity was associated with a reduction in eNOS
      phosphorylation at Serine-1177 and increased phosphorylation at Threonine-495.
      This was paralleled with an induction in arginase-2 expression and activity, and
      decreased l-arginine transport. In hypoxia the arginase inhibition, restored NO
      synthesis and l-arginine transport, without changes in the eNOS post
      translational modification status. Hypoxia increased arginase-2/eNOS
      colocalization, and eNOS redistribution to the cell periphery. Altogether these
      data reinforce the thought that eNOS cell location, post-translational
      modification and substrate availability are important mechanisms regulating eNOS
      activity. If these mechanisms occur in pregnancy diseases where feto-placental
      oxygen levels are reduced remains to be clarified.

PMID- 21962306
TI  - The importance of being elderly-some thoughts on the care of geriatric patients.

PMID- 21962307
TI  - Weight and weight change-think about the context.

PMID- 21962308
TI  - Selecting a mentor: a guide for residents, fellows, and young physicians.

PMID- 21962309
TI  - Half a century of hydrochlorothiazide: facts, fads, fiction, and follies.
AB  - Hydrochlorothiazide (HCTZ) has become by far the most commonly prescribed
      antihypertensive drug in the US. In 2008, 47.8 million prescriptions were written
      for HCTZ alone and 87.1 million prescriptions for HCTZ combinations. However,
      there is no evidence that HCTZ in its usual dose of 12.5-25 mg daily reduces
      myocardial infarction, stroke, or death. In a meta-analysis of 19 randomized
      trials with over 1400 patients, the 24-hour decrease in blood pressure with HCTZ
      was inferior to angiotensin-converting enzyme inhibitors, angiotensin receptor
      blockers, beta-blockers, and calcium channel blockers (P <.001 for all). Even in
      combination with an angiotensin-converting enzyme inhibitor, HCTZ was found to
      reduce morbidity and mortality less well than a calcium channel blocker. As
      measured by the adherence rate, thiazides are less well tolerated than any other
      drug class. Because outcome data at the usual daily dose of 12.5-25 mg are
      lacking, antihypertensive efficacy is paltry, and adherence is poor, HCTZ is an
      inappropriate first-line drug in hypertension. If a "thiazide-type" diuretic is
      indicated, either chlorthalidone or indapamide should be selected.

PMID- 21962310
TI  - An enlarging ulcer.

PMID- 21962311
TI  - If at first you don't perceive....the importance of repeating an ECG when a
      myocardial infarction is suspected.

PMID- 21962312
TI  - A tight spot. Aberrant right subclavian artery compressing the esophagus.

PMID- 21962313
TI  - Incremental weight loss improves cardiometabolic risk in extremely obese adults.
AB  - OBJECTIVE: Excessively obese adults often acquire many metabolic disorders that
      put them at high risk for developing type 2 diabetes mellitus and cardiovascular
      disease. We investigated the hypothesis that cardiometabolic risk in a primary
      care cohort of 208 excessively obese adults (body mass index 40-60 kg/m(2), 48
      with type 2 diabetes mellitus) would deteriorate with additional weight gain and
      improve incrementally beginning with 5% weight reduction. METHODS: Further
      analysis of the Louisiana Obese Subjects Study of excessively obese patients
      enrolled and followed during 2005-2008 is reported. RESULTS: Weight loss
      correlated significantly with improvements in fasting plasma glucose,
      triglycerides, high- and low-density lipoprotein cholesterol, uric acid, alanine
      aminotransferase, lactate dehydrogenase, and high-sensitivity C-reactive protein.
      Most parameters deteriorated with weight gain and progressively improved with 5%
      or more weight loss. Except for low-density lipoprotein cholesterol, all risk
      factors significantly improved with >= 20% loss of body weight. Among patients
      who had not been diagnosed with type 2 diabetes mellitus and had normoglycemia at
      baseline, median fasting plasma glucose increased significantly (13%) with stable
      or gained weight at 1 year, but did not change significantly with reduced weight.
      Although glucose levels did not change significantly in patients with type 2
      diabetes mellitus who gained weight, a decline beginning after 5% weight
      reduction culminated in 25% glucose reduction with >= 20% weight loss. Resting
      blood pressure declined independently of weight change. CONCLUSION: Very obese
      adults can improve their cardiometabolic risk under primary care weight
      management. Incremental success may help motivate further therapeutic weight
      reduction.

PMID- 21962314
TI  - Long-term trends in short-term outcomes in acute myocardial infarction.
AB  - BACKGROUND: The objectives of this study were to examine the magnitude of, and 20
      year trends in, age differences in short-term outcomes among men and women
      hospitalized with acute myocardial infarction (AMI) in central Massachusetts.
      METHODS: The study population consisted of 5907 male and 4406 female residents of
      the Worcester, MA, metropolitan area hospitalized at all greater Worcester
      medical centers with AMI between 1986 and 2005. RESULTS: Overall, among both men
      and women, older patients were significantly more likely to have developed atrial
      fibrillation, heart failure, and to have died during hospitalization and within
      30 days after admission compared with patients aged <65 years. Among men, age
      differences in the risk of developing atrial fibrillation have widened over the
      past 2 decades, while differences in the risk of developing cardiogenic shock
      have narrowed for men 75 years and older as compared with those aged <65 years.
      Among women, age differences in the risk of developing these major complications
      of AMI have not changed significantly over time. Age differences in short-term
      mortality have remained relatively unchanged over the past 20 years in both
      sexes, although individuals of all ages have experienced decreases in short-term
      death rates over this period. CONCLUSIONS: Elderly men and women are more likely
      to experience adverse short-term outcomes after AMI, and age differences in short
      term mortality rates have remained relatively unchanged in both sexes over the
      past 20 years. More targeted treatment approaches during hospitalization for AMI
      and thereafter are needed for older patients to improve their prognosis.

PMID- 21962315
TI  - Derivation and validation of a simple model to identify venous thromboembolism
      risk in medical patients.
AB  - BACKGROUND: Fewer than half of eligible hospitalized medical patients receive
      appropriate venous thromboembolism (VTE) prophylaxis. One reason for this low
      rate is the complexity of existing risk assessment models. A simple set of easily
      identifiable risk factors that are highly predictive of VTE among hospitalized
      medical patients may enhance appropriate thromboprophylaxis. METHODS: Electronic
      medical record interrogation was performed to identify medical admissions from
      January 1, 2000-December 31, 2007 (n=143,000), and those patients with
      objectively confirmed VTE during hospitalization or within 90 days following
      discharge. Putative risk factors most predictive of VTE were identified, and a
      risk assessment model (RAM) was derived; 46,000 medicine admissions from January
      1, 2008-December 31, 2009 served as a validation cohort to test the predictive
      ability of the RAM. The newly derived RAM was compared with a published VTE
      assessment tool (Kucher Score). RESULTS: Four risk factors: previous VTE; an
      order for bed rest; peripherally inserted central venous catheterization line;
      and a cancer diagnosis, were the minimal set most predictive of hospital
      associated VTE (area under the receiver operating characteristic curve
      [AUC]=0.874; 95% confidence interval [CI], 0.869-0.880). These risk factors upon
      validation in a separate population (validation cohort) retained an AUC=0.843;
      95% CI, 0.833-0.852. The ability of the 4-element RAM to identify patients at
      risk of developing VTE within 90 days was superior to the Kucher Score.
      CONCLUSIONS: The 4-element RAM identified in this study may be used to identify
      patients at risk for VTE and improve rates of thromboprophylaxis. This simple and
      accurate RAM is an alternative to more complicated published VTE risk assessment
      tools that currently exist.

PMID- 21962316
TI  - Opioid use, misuse, and abuse in patients labeled as fibromyalgia.
AB  - BACKGROUND: As pain is the cardinal symptom of fibromyalgia, it is logical that
      treatments directed toward pain relief will be commonly used. Analgesic drug
      therapy remains the traditional treatment intervention for most chronic pain
      conditions, with a progressive increased use of opioids in the past 20 years.
      Concerns about efficacy, risk-benefit ratio, and possible long-term effects of
      chronic opioid therapy have been raised. There is limited information about
      opioid treatment in fibromyalgia, with all current guidelines discouraging opioid
      use. METHODS: A chart review of all patients referred to a tertiary care pain
      center clinic with a referring diagnosis of fibromyalgia was conducted to
      evaluate use of opioid medications. RESULTS: We have recorded opioid use by 32%
      of 457 patients referred to a multidisciplinary fibromyalgia clinic, with over
      two thirds using strong opioids. Opioid use was more commonly associated with
      lower education, unemployment, disability payments, current unstable psychiatric
      disorder, a history of substance abuse, and previous suicide attempts.
      CONCLUSION: We have observed negative health and psychosocial status in patients
      using opioids and labeled as fibromyalgia. Prolonged use of opioids in
      fibromyalgia requires evaluation.

PMID- 21962317
TI  - N-terminal pro B-type natriuretic peptide identifies patients with chest pain at
      high long-term cardiovascular risk.
AB  - BACKGROUND: Little is known about the long-term prognostic value of N-terminal
      pro B-type natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) in low
      risk patients with chest pain. METHODS: Between June 1997 and January 2000, a
      standard rule-out protocol was performed in patients presenting to the emergency
      department within 6 hours of onset of chest pain with a normal or nondiagnostic
      electrocardiogram (ECG) on admission at the Academic Medical Center Amsterdam, VU
      University Medical Center Amsterdam and Medical Center Alkmaar, The Netherlands.
      Patients with acute coronary syndrome were identified by troponin T, recurrent
      angina, and serial ECGs. CRP and NT-proBNP on admission were measured using
      standardized methods. RESULTS: A total of 524 patients were included (145 with
      acute coronary syndrome and 379 with rule-out acute coronary syndrome). Long-term
      follow-up was successfully carried out in 96% of the study population. Death
      occurred in 78 patients (15%), 43 (11%) in the rule-out acute coronary syndrome
      group and 35 (24%) in the acute coronary syndrome group (P<.001). In the rule-out
      acute coronary syndrome group, 21 patients (42%) died of a cardiovascular cause
      compared with 24 patients (69%) in the acute coronary syndrome group (P<.001). In
      multivariate Cox regression analysis, age more than 65 years, previous myocardial
      infarction, known chronic heart failure, a nondiagnostic ECG on admission, and
      elevated NT-proBNP levels (>87 pg/mL, as derived from the receiver operating
      characteristic curve) were independent predictors of long-term cardiovascular
      mortality in the rule-out acute coronary syndrome group. In the acute coronary
      syndrome group, these predictors were age more than 65 years, documented coronary
      artery disease, and elevated NT-proBNP levels. Elevated levels of CRP were an
      independent predictor for cardiovascular mortality in patients with rule-out
      acute coronary syndrome at 3-year follow-up only. In patients with rule-out acute
      coronary syndrome with normal CRP and NT-proBNP levels, the cardiovascular
      mortality incidence rate was 4.7 per 1000 person-years, compared with a death
      rate of 20 in patients with both biomarkers elevated, which was comparable to the
      17.9 per 1000 person-years incidence rate in patients with acute coronary
      syndrome. CONCLUSION: A positive biomarker panel discriminates patients with rule
      out acute coronary syndrome chest pain with a normal or nondiagnostic ECG who
      have a high risk for long-term cardiovascular mortality.

PMID- 21962318
TI  - The hematocrit level in upper gastrointestinal hemorrhage: safety of endoscopy
      and outcomes.
AB  - OBJECTIVE: In patients with acute upper gastrointestinal hemorrhage, standard
      practice is to transfuse packed red blood cells, often to an arbitrary level of
      hemoglobin or hematocrit (typically 10 g/dL and 30%, respectively) before
      endoscopy. Therefore, we aimed to determine first whether performing endoscopy in
      patients with upper gastrointestinal hemorrhage and a low hematocrit is safe and
      whether it predicts outcomes. METHODS: This cohort study included patients with
      carefully defined upper gastrointestinal hemorrhage captured in our
      gastrointestinal Healthcare Registry who underwent esophagogastroduodenoscopy.
      Patients were placed into 2 groups: low hematocrit (<30%) or high hematocrit
      (>30%). Clinical variables and outcomes, including cardiovascular events,
      intensive care unit transfer, and death, were measured. RESULTS: A total of 920
      patients meeting entry criteria were identified. Baseline features among those
      with a low and high hematocrit were identical. Eight cardiovascular events
      occurred during or after esophagogastroduodenoscopy, including 5 of 587 (1%) in
      the less than 30% hematocrit group and 3 of 333 (1%) in the greater than 30%
      hematocrit group (P=.29). Blood transfusions were more common in the low
      hematocrit group (74% vs 24%, P<.001). However, correlation between the amount of
      blood transfused and hematocrit level was poor, and the number units of blood
      transfused was highly variable. There was no significant mortality difference in
      the 2 hematocrit groups. CONCLUSION: Most patients with upper gastrointestinal
      hemorrhage presented with a hematocrit less than 30%. Performing endoscopy in
      patients with a low hematocrit was clearly safe; these data strongly imply that
      waiting for the hematocrit to reach a certain level before endoscopy is not
      necessary.

PMID- 21962319
TI  - Lessons from my first patient.

PMID- 21962320
TI  - Short-term efficacy and safety of vasopressin receptor antagonists for treatment
      of hyponatremia.
AB  - BACKGROUND: We performed a meta-analysis to systematically measure efficacy and
      safety of vasopressin receptor antagonists (VRAs) tested in randomized controlled
      trials for treatment of hyponatremia. METHODS: MEDLINE, ClinicalTrials.gov, and
      scientific abstracts were searched without language restriction. Two authors
      independently screened citations and extracted data on patient characteristics,
      quality of reports, and efficacy and safety endpoints. RESULTS: Eleven trials
      were identified (1094 patients). By meta-analysis, VRAs achieved a net increase
      in serum sodium concentration ([Na(+)](serum)) relative to placebo of 3.3 mEq/L
      at day 1 (95% confidence interval [CI], 2.7-3.8), and 4.2 mEq/L at day 2 (95% CI,
      3.6-4.8), persisting at days 3-5. Larger net increases in [Na(+)](serum) at days
      1-4 were observed in euvolemic hyponatremia and with higher doses. VRAs induced a
      net increase in effective water clearance relative to placebo of 1244 mL at day 1
      (95% CI, 920-1567), persisting at days 2 and 4. VRAs were associated with odds
      ratios of 3.0 for overly rapid correction of [Na(+)](serum) (P <.001), 7.8 for
      development of hypernatremia (P <.001), 3.3 for thirst development (P <.001), and
      2.2 for postural hypotension (P=.04). CONCLUSIONS: Short-term use of VRAs in
      treating hyponatremia was successful at raising [Na(+)](serum). Additional
      experience is required to guide their optimal use and minimize safety concerns.

PMID- 21962321
TI  - Recertification for grandfathers.

PMID- 21962322
TI  - Contraindications to pharmacologic therapies for gout.

PMID- 21962323
TI  - Steroid for gout: myth or elixir?

PMID- 21962325
TI  - Work ergonomics and e-thrombosis: a grievous yet preventable combination.

PMID- 21962326
TI  - Invasive mycoses: evolving challenges and opportunities in antifungal therapy
      (multimedia activity).

PMID- 21962327
TI  - Comparison of four different mobile devices for measuring heart rate and ECG with
      respect to aspects of usability and acceptance by older people.
AB  - In the area of product design and usability, most products are developed for the
      mass-market by technically oriented designers and developers for use by persons
      who themselves are also technically adept by today's standards. The demands of
      older people are commonly not given sufficient consideration within the early
      developmental process. In the present study, the usability and acceptability of
      four different devices meant to be worn for the measurement of heart rate or ECG
      were analyzed on the basis of qualitative subjective user ratings and structured
      interviews of twelve older participants. The data suggest that there was a
      relatively high acceptance concerning these belts by older adults but none of the
      four harnesses was completely usable. Especially problematic to the point of
      limiting satisfaction among older subjects were problems encountered while
      adjusting the length of the belt and/or closing the locking mechanism. The two
      devices intended for dedicated heart rate recording yielded the highest user
      ratings for design, and were clearly preferred for extended wearing time. Yet for
      all the devices participants identified several important deficiencies in their
      design, as well as suggestions for improvement. We conclude that the creation of
      an acceptable monitoring device for older persons requires designers and
      developers to consider the special demands and abilities of the target group.

PMID- 21962328
TI  - [The importance of adequately evaluating pain].

PMID- 21962329
TI  - Modeling competitive cytokine adsorption dynamics within hemoadsorption beads
      used to treat sepsis.
AB  - Extracorporeal blood purification is a promising therapeutic modality for sepsis,
      a potentially fatal, dysfunctional immunologic state caused by infection. Removal
      of inflammatory mediators such as cytokines from the blood may help attenuate
      hyper-inflammatory signaling during sepsis and improve patient outcomes. We are
      developing a hemoadsorption device to remove cytokines from the circulating blood
      using biocompatible, porous sorbent beads. In this work, we investigated whether
      competitive adsorption of serum solutes affects cytokine removal dynamics within
      the hemoadsorption beads. Confocal laser scanning microscopy (CLSM) was used to
      quantify intraparticle adsorption profiles of fluorescently labeled IL-6 in horse
      serum, and results were compared to predictions of a two component competitive
      adsorption model. Supraphysiologic IL-6 concentrations were necessary to obtain
      adequate CLSM signal, therefore unknown model parameters were fit to CLSM data at
      high IL-6 concentrations, and the fitted model was used to simulate cytokine
      adsorption behavior at physiologically relevant levels which were below the
      microscopy detection threshold. CLSM intraparticle IL-6 adsorption profiles
      agreed with predictions of the competitive adsorption model, indicating
      displacement of cytokine by high affinity serum solutes. However, competitive
      adsorption effects were predicted using the model to be negligible at physiologic
      cytokine concentrations associated with hemoadsorption therapy.

PMID- 21962330
TI  - Simultaneous analysis of pesticides from different chemical classes by using a
      derivatisation step and gas chromatography-mass spectrometry.
AB  - This work presents a new method to analyse simultaneously by GC-MS 31 pesticides
      from different chemical classes (2,4 D, 2,4 MCPA, alphacypermethrin, bifenthrin,
      bromoxynil, buprofezin, carbaryl, carbofuran, clopyralid, cyprodinil,
      deltamethrin dicamba, dichlobenil, dichlorprop, diflufenican, diuron, fenoxaprop,
      flazasulfuron, fluroxypyr, ioxynil, isoxaben, mecoprop-P, myclobutanil, oryzalin,
      oxadiazon, picloram, tau-fluvalinate tebuconazole, triclopyr, trifluralin and
      trinexapac-p-ethyl). This GC-MS method will be applied to the analysis of passive
      samplers (Tenax((r)) tubes and SPME fiber) used for the evaluation of the indoor
      and outdoor atmospheric contamination by non-agricultural pesticides. The method
      involves a derivatisation step for thermo-labile or polar pesticides. Different
      agents were tested and MtBSTFA (N-(t-butyldimethylsilyl)-N
      methyltrifluoroacetamide), a sylilation agent producing very specific fragments
      [M-57], was retained. However, diuron could not be derivatised and the isocyanate
      product was used for identification and quantification. Pesticides which did not
      need a derivatisation step were not affected by the presence of the
      derivatisation agent and they could easily be analysed in mixture with
      derivatised pesticides. The method can be coupled to a thermal-desorption unit or
      to SPME extraction for a multiresidue analysis of various pesticides in
      atmospheric samples.

PMID- 21962331
TI  - DeltaFosB enhances the rewarding effects of cocaine while reducing the pro
      depressive effects of the kappa-opioid receptor agonist U50488.
AB  - BACKGROUND: Elevated expression of the transcription factor DeltaFosB accompanies
      repeated exposure to drugs of abuse, particularly in brain areas associated with
      reward and motivation (e.g., nucleus accumbens). The persistent effects of
      DeltaFosB on target genes might play an important role in the development and
      expression of behavioral adaptations that characterize addiction. This study
      examines how DeltaFosB influences the responsiveness of the brain reward system
      to rewarding and aversive drugs. METHODS: We used the intracranial self
      stimulation paradigm to assess the effects of cocaine in transgenic mice with
      inducible overexpression of DeltaFosB in striatal regions (including nucleus
      accumbens and dorsal striatum). Mice implanted with lateral hypothalamic
      stimulating electrodes were trained with the "rate-frequency" procedure for
      intracranial self-stimulation to determine the frequency at which stimulation
      becomes rewarding (threshold). RESULTS: A dose-effect analysis of cocaine effects
      revealed that mice overexpressing DeltaFosB show increased sensitivity to the
      rewarding (threshold-lowering) effects of the drug, compared with littermate
      control subjects. Interestingly, mice overexpressing DeltaFosB were also less
      sensitive to the pro-depressive (threshold-elevating) effects of U50488, a kappa
      opioid agonist known to induce dysphoria and stress-like effects in rodents.
      CONCLUSIONS: These data suggest that induction of DeltaFosB in striatal regions
      has two important behavioral consequences-increased sensitivity to drug reward,
      and reduced sensitivity to aversion-producing a complex phenotype that shows
      signs of vulnerability to addiction as well as resilience to stress.

PMID- 21962333
TI  - The evolution of adult height across Spanish regions, 1950-1980: a new source of
      data.
AB  - We present new evidence concerning the evolution of adult height across Spanish
      regions for the 1950-1980 male and female birth cohorts, using the augmented
      sample of the European Community Household Panel (ECHP) for Spain. This augmented
      sample, available only for the year 2000, contains self-reported height data
      representative at the Autonomous Community level. The average heights of these
      two sets of birth cohorts, female and male, are found to increase by 1.7 and
      1.6cm/decade, respectively. Making available a new dataset of quinquennial mean
      heights will allow researchers to study the determinants of population heights by
      means of a within-country analysis.

PMID- 21962332
TI  - Adverse rearing environments and neural development in children: the development
      of frontal electroencephalogram asymmetry.
AB  - BACKGROUND: Children raised in institutional settings experience marked
      deprivation in social and environmental stimulation. This deprivation may disrupt
      brain development in ways that increase risk for psychopathology. Differential
      hemispheric activation of the frontal cortex is an established biological
      substrate of affective style that is associated with internalizing
      psychopathology. Previous research has never characterized the development of
      frontal electroencephalogram asymmetry in children or evaluated whether adverse
      rearing environments alter developmental trajectories. METHODS: A sample of 136
      children (mean age = 23 months) residing in institutions in Bucharest, Romania,
      and a sample of community control subjects (n = 72) participated. Half of
      institutionalized children were randomized to a foster care intervention.
      Electroencephalogram data were acquired at study entry and at ages 30, 42, and 96
      months. A structured diagnostic interview of psychiatric disorders was completed
      at 54 months. RESULTS: Children exhibited increases in right relative to left
      hemisphere frontal activation between the second and fourth years of life,
      followed by an increase in left relative to right hemisphere activation. Children
      reared in institutions experienced a prolonged period of increased right
      hemisphere activation and a blunted rebound in left frontal activation. Foster
      care placement was associated with improved developmental trajectories but only
      among children placed before 24 months. The development trajectory of frontal
      electroencephalogram asymmetry in early childhood predicted internalizing
      symptoms at 54 months. CONCLUSIONS: Exposure to adverse rearing environments can
      alter brain development, culminating in heightened risk for psychopathology.
      Interventions delivered early in life have the greatest potential to mitigate the
      long-term effects of these environments.

PMID- 21962334
TI  - Fracture of the talus as a complication of subtalar arthroereisis.
AB  - Subtalar joint arthroereisis remains a popular procedure for a flexible flatfoot
      deformity. Potential complications of the procedure have been discussed in
      published reports and are often believed to have resulted from shortcomings
      related to the mechanical properties of the biomaterial, implant size, and/or
      implant placement. In the present report, we describe the case of a talar neck
      fracture with migration of the implant after subtalar joint arthroereisis
      performed 10 years earlier. The 19-year-old patient was treated with implant
      removal and open reduction internal fixation and bone void filler and recovered
      unremarkably thereafter.

PMID- 21962335
TI  - Surveillance technology: an alternative to physical restraints? A qualitative
      study among professionals working in nursing homes for people with dementia.
AB  - BACKGROUND: Working with surveillance technology as an alternative to traditional
      restraints creates obvious differences in the way care is organised. It is not
      clear whether professional caregivers find working with surveillance technology
      useful and workable and whether surveillance technology is indeed used to
      diminish restraint use. OBJECTIVES: The aim of this study was to obtain an
      insight into the view of Dutch dementia care professionals on the feasibility of
      surveillance technology as an alternative to physical restraints. DESIGN:
      Qualitative study. SETTING: The study was carried out in seven nursing homes for
      people with dementia in The Netherlands. PARTICIPANTS AND METHODS: Semi
      structured interviews were held with nine key persons from seven nursing homes
      for people with dementia. Also, six focus group discussions were held with groups
      of nurses and two focus group discussions were held with multidisciplinary teams.
      RESULTS: The dementia care professionals named three different ways in which
      surveillance technology can be used: to provide safety in general, to provide
      additional safety, and to provide more freedom for the residents. In addition to
      this, the dementia care professionals mentioned four limitations in the use of
      surveillance technology: it is unable to prevent falling, it cannot guarantee
      quick help, it does not always work properly, and it could violate privacy.
      CONCLUSION: Dementia care professionals consider surveillance technology
      supplemental to physical restraints, rather than as an alternative. Improvement
      of devices and education of care professionals might increase the support for
      using surveillance technology as an alternative to physical restraints.

PMID- 21962336
TI  - Effects of an interpersonal-psychotherapy-oriented childbirth education programme
      for Chinese first-time childbearing women at 3-month follow up: randomised
      controlled trial.
AB  - BACKGROUND: Developing a sense of well-being and achieving maternal role
      competence are considered critical components of maternal adaptation. Given the
      growing evidence of postpartum depression and its devastating effects, effective
      childbirth psychoeducation programme to promote maternal role competence,
      psychological well-being and prevent postpartum depression is essential and of an
      urgent priority. OBJECTIVE: To examine the effects of an interpersonal
      psychotherapy oriented childbirth education programme on social support, maternal
      role competence, postpartum depression and psychological well-being in Chinese
      first-time childbearing women at three-month postpartum. DESIGN, SETTING AND
      PARTICIPANTS: Randomised controlled trial in a regional teaching hospital,
      Guangzhou, China with 194 first-time pregnant women, of whom 96 received
      interpersonal-psychotherapy-oriented childbirth education programme and 98
      standard care. The intervention was developed from principles of interpersonal
      psychotherapy which consisted of two 90-min antenatal classes and a telephone
      follow-up within two weeks after delivery. Outcomes measurements included
      Perceived Social Support Scale, Parenting Sense of Competence Scale-Efficacy
      subscale, Edinburgh Postnatal Depression Scale and General Health Questionnaire,
      were compared over three-month follow up. RESULTS: The study group had
      significantly better improvement on perceived social support (p<0.01), maternal
      role competence (p<0.01), postpartum depressive symptoms (p<0.01) and
      psychological well-being (p<0.01) when compared with the control group. The study
      group also had significantly higher level of social support (t=2.33, p=0.021),
      maternal role competence (t=2.43, p=0.016) and less depressive symptoms (t=-2.39,
      p=0.018) at three-month postpartum when compared with the control group.
      DISCUSSION: The childbirth psychoeducation programme can substantially benefit
      first time Chinese mothers. It could be implemented as a routine care with
      ongoing evaluation. Future studies could focus on women in lower social classes,
      with multiple pregnancy and complicated pregnancy.

PMID- 21962337
TI  - Durable molecular response despite F317L and E255K mutations: Successful
      treatment of chronic myeloid leukemia with sequential imatinib, nilotinib and
      dasatinib.

PMID- 21962338
TI  - Aplastic anemia in association with a lymphoproliferative neoplasm: coincidence
      or causality?

PMID- 21962339
TI  - Novel head-to-head gene fusion of MLL with ZC3H13 in a JAK2 V617F-positive
      patient with essential thrombocythemia without blast cells.

PMID- 21962341
TI  - Review of robust multivariate statistical methods in high dimension.
AB  - General ideas of robust statistics, and specifically robust statistical methods
      for calibration and dimension reduction are discussed. The emphasis is on
      analyzing high-dimensional data. The discussed methods are applied using the
      packages chemometrics and rrcov of the statistical software environment R. It is
      demonstrated how the functions can be applied to real high-dimensional data from
      chemometrics, and how the results can be interpreted.

PMID- 21962342
TI  - Stability-based biomarker selection.
AB  - Biomarker identification, i.e., finding those variables that indicate true
      differences between two or more populations, is an ever more important topic in
      the omics sciences. In most cases, the number of variables far exceeds the number
      of samples, making biomarker identification extremely difficult. We present a
      strategy based on the stability of putative biomarkers under perturbation of the
      data, and show that in several cases important gains can be achieved. The
      strategy is very general and can be applied with all common biomarker
      identification methods; it also has the advantage that it does not rely on error
      estimates from crossvalidation, that in this setting tend to be highly variable.

PMID- 21962343
TI  - A liquid-liquid extraction procedure followed by a low temperature purification
      step for the analysis of macrocyclic lactones in milk by liquid chromatography
      tandem mass spectrometry and fluorescence detection.
AB  - In this work a method is proposed and demonstrated for the analysis of the
      macrocyclic lactones abamectin, doramectin, eprinomectin, ivermectin and
      moxidectin in bovine milk by liquid chromatography coupled to mass spectrometry
      (LC-MS/MS) and liquid chromatography with fluorescence detection (LC-FL). The
      method is based on liquid-liquid extraction followed by a low temperature
      purification (LLE-LTP) step. Moreover, the proposed method was validated
      according to the Commission Decision 2002/657/EC, using LC-MS/MS and LC-FL for
      confirmatory and quantitative analysis, respectively. For LC-MS/MS the recovery
      rates observed ranged from 101.2 to 141.6% with coefficient of variation from 2.6
      to 19.8%. For LC-FL the recovery rates observed ranged from 100.2 to 105% and
      coefficient of variations from 2.9 to 8.8%. Matrix effects were negligible due to
      the low temperature purification step. The quantification limits were far below
      the maximum limits established by regulations of all countries consulted. The
      proposed method proved to be simple, easy, and adequate for high-throughput
      analysis of a large number of samples per day at low cost.

PMID- 21962344
TI  - Comparison of various chemometric approaches for large near infrared
      spectroscopic data of feed and feed products.
AB  - In the present study, different multivariate regression techniques have been
      applied to two large near-infrared data sets of feed and feed ingredients in
      order to fulfil the regulations and laws that exist about the chemical
      composition of these products. The aim of this paper was to compare the
      performances of different linear and nonlinear multivariate calibration
      techniques: PLS, ANN and LS-SVM. The results obtained show that ANN and LS-SVM
      are very powerful methods for non-linearity but LS-SVM can also perform quite
      well in the case of linear models. Using LS-SVM an improvement of the RMS for
      independent test sets of 10% is obtained in average compared to ANN and of 24%
      compared to PLS.

PMID- 21962345
TI  - Multivariate control charts based on net analyte signal (NAS) and Raman
      spectroscopy for quality control of carbamazepine.
AB  - Raman spectroscopy and control charts based on the net analyte signal (NAS) were
      applied to polymorphic characterization of carbamazepine. Carbamazepine presents
      four polymorphic forms: I-IV (dihydrate). X-ray powder diffraction was used as a
      reference technique. The control charts were built generating three charts: the
      NAS chart that corresponds to the analyte of interest (form III in this case),
      the interference chart that corresponds to the contribution of other compounds in
      the sample and the residual chart that corresponds to nonsystematic variations.
      For each chart, statistical limits were developed using samples within the
      quality specifications. It was possible to identify the different polymorphic
      forms of carbamazepine present in pharmaceutical formulations. Thus, an
      alternative method for the quality monitoring of the carbamazepine polymorphic
      forms after the crystallization process is presented.

PMID- 21962346
TI  - On the increase of predictive performance with high-level data fusion.
AB  - The combination of the different data sources for classification purposes, also
      called data fusion, can be done at different levels: low-level, i.e.
      concatenating data matrices, medium-level, i.e. concatenating data matrices after
      feature selection and high-level, i.e. combining model outputs. In this paper the
      predictive performance of high-level data fusion is investigated. Partial least
      squares is used on each of the data sets and dummy variables representing the
      classes are used as response variables. Based on the estimated responses y(j) for
      data set j and class k, a Gaussian distribution p(g(k)|y(j)) is fitted. A
      simulation study is performed that shows the theoretical performance of high
      level data fusion for two classes and two data sets. Within group correlations of
      the predicted responses of the two models and differences between the predictive
      ability of each of the separate models and the fused models are studied. Results
      show that the error rate is always less than or equal to the best performing
      subset and can theoretically approach zero. Negative within group correlations
      always improve the predictive performance. However, if the data sets have a joint
      basis, as with metabolomics data, this is not likely to happen. For equally
      performing individual classifiers the best results are expected for small within
      group correlations. Fusion of a non-predictive classifier with a classifier that
      exhibits discriminative ability lead to increased predictive performance if the
      within group correlations are strong. An example with real life data shows the
      applicability of the simulation results.

PMID- 21962347
TI  - Random projection for dimensionality reduction--applied to time-of-flight
      secondary ion mass spectrometry data.
AB  - Random projection (RP) is a simple and fast linear method for dimensionality
      reduction of high-dimensional multivariate data, independent from the data. The
      method is briefly described and a new memory-saving algorithm is presented for
      the generation of random projection vectors. Application of RP to data from
      scanning experiments with a time-of-flight secondary ion mass spectrometer (TOF
      SIMS) showed that data reduced by RP have a satisfying discriminant property for
      separating target material and minerals without using any knowledge about the
      composition of the sample. A selection method--based on low dimensional RP data-
      is described and successfully tested for automatic recognition of characteristic,
      diverse locations of a sample surface. RP is demonstrated as an unbiased,
      powerful method, especially for large data sets, severe hardware restrictions
      (such as in space experiments) or the need for fast data evaluation of
      hyperspectral data.

PMID- 21962348
TI  - Data integration and network reconstruction with ~omics data using Random Forest
      regression in potato.
AB  - In the post-genomic era, high-throughput technologies have led to data collection
      in fields like transcriptomics, metabolomics and proteomics and, as a result,
      large amounts of data have become available. However, the integration of these
      ~omics data sets in relation to phenotypic traits is still problematic in order
      to advance crop breeding. We have obtained population-wide gene expression and
      metabolite (LC-MS) data from tubers of a diploid potato population and present a
      novel approach to study the various ~omics datasets to allow the construction of
      networks integrating gene expression, metabolites and phenotypic traits. We used
      Random Forest regression to select subsets of the metabolites and transcripts
      which show association with potato tuber flesh color and enzymatic discoloration.
      Network reconstruction has led to the integration of known and uncharacterized
      metabolites with genes associated with the carotenoid biosynthesis pathway. We
      show that this approach enables the construction of meaningful networks with
      regard to known and unknown components and metabolite pathways.

PMID- 21962349
TI  - Baseline correction methods to deal with artifacts in femtosecond transient
      absorption spectroscopy.
AB  - In femtosecond transient absorption spectroscopy, artifact contributions are
      usually observed at ultra-short time scale. These complex signals are very
      challenging because of their nature, related to ultrafast phenomena, and because
      they strongly distort the structure of the spectrokinetic data. The purpose of
      this work is to evaluate the potential of baseline correction methods for
      femtosecond transient absorption spectroscopy data pre-processing. Indeed,
      artifacts removal should ideally be performed before multivariate data analysis.
      The work is thus mainly focused on two different approaches which are filtering
      by discrete wavelet transform, on the one hand, and smoothing by asymmetric least
      squares, on the other hand. The results obtained both on simulated data and on
      femtosecond pump-probe spectroscopy data are discussed. It can be concluded that
      asymmetric least squares smoothing procedure turns out to perform satisfactory
      for artifacts removal. Indeed, only mild discrepancies are observed in the
      transient spectra and, most important, good recovery of the kinetics is obtained
      at ultra-short time scale.

PMID- 21962350
TI  - Non-linear modeling of 1H NMR metabonomic data using kernel-based orthogonal
      projections to latent structures optimized by simulated annealing.
AB  - Linear multivariate projection methods are frequently applied for predictive
      modeling of spectroscopic data in metabonomic studies. The OPLS method is a
      commonly used computational procedure for characterizing spectral metabonomic
      data, largely due to its favorable model interpretation properties providing
      separate descriptions of predictive variation and response-orthogonal structured
      noise. However, when the relationship between descriptor variables and the
      response is non-linear, conventional linear models will perform sub-optimally. In
      this study we have evaluated to what extent a non-linear model, kernel-based
      orthogonal projections to latent structures (K-OPLS), can provide enhanced
      predictive performance compared to the linear OPLS model. Just like its linear
      counterpart, K-OPLS provides separate model components for predictive variation
      and response-orthogonal structured noise. The improved model interpretation by
      this separate modeling is a property unique to K-OPLS in comparison to other
      kernel-based models. Simulated annealing (SA) was used for effective and
      automated optimization of the kernel-function parameter in K-OPLS (SA-K-OPLS).
      Our results reveal that the non-linear K-OPLS model provides improved prediction
      performance in three separate metabonomic data sets compared to the linear OPLS
      model. We also demonstrate how response-orthogonal K-OPLS components provide
      valuable biological interpretation of model and data. The metabonomic data sets
      were acquired using proton Nuclear Magnetic Resonance (NMR) spectroscopy, and
      include a study of the liver toxin galactosamine, a study of the nephrotoxin
      mercuric chloride and a study of Trypanosoma brucei brucei infection. Automated
      and user-friendly procedures for the kernel-optimization have been incorporated
      into version 1.1.1 of the freely available K-OPLS software package for both R and
      Matlab to enable easy application of K-OPLS for non-linear prediction modeling.

PMID- 21962351
TI  - Calibration transfer for excitation-emission fluorescence measurements.
AB  - The main part of the wide array of different calibration transfer methods found
      in literature is dedicated to two-way data arrangements (m*n matrices). Less work
      has been done within the area of calibration transfer for three-way data
      structures (m*n*l tensors) such as calibrations made for excitation-emission
      matrix (EEM) fluorescence spectra. There are two possible ways to attack the
      problem for EEM transfer. Either the tensors are unfolded to two-way data,
      whereby the existing methods can be applied, or new methods dedicated to three
      way calibration transfer have to be developed. This paper presents and compares
      both. It was possible to make a local linear pixel-based model that could be used
      for transfer of EEM's. This new method has a similar performance to the classical
      methods found in literature, direct- and piecewise direct standardization. The
      three-way advantages made it possible to use as few as four samples to build
      useable transfer models. Care has to be taken though when choosing the samples.
      When subset recalibration of the systems is compared to calibration transfer,
      better performance is seen for the transferred calibrations. Overall the three
      way calibration transfer methods have a slightly better performance than the two
      way methods.

PMID- 21962352
TI  - Mid-infrared spectrometry of milk for dairy metabolomics: a comparison of two
      sampling techniques and effect of homogenization.
AB  - Milk production is a dominant factor in the metabolism of dairy cows involving a
      very intensive interaction with the blood circulation. As a result, the extracted
      milk contains valuable information on the metabolic status of the cow. On-line
      measurement of milk components during milking two or more times a day would
      promote early detection of systemic and local alterations, thus providing a great
      input for strategic and management decisions. The objective of this study was to
      investigate the potential of mid-infrared (mid-IR) spectroscopy to measure the
      milk composition using two different measurement modes: micro attenuated total
      reflection (MUATR) and high throughput transmission (HTT). Partial least squares
      (PLS) regression was used for prediction of fat, crude protein, lactose and urea
      after preprocessing IR data and selecting the most informative wavenumber
      variables. The prediction accuracies were determined separately for raw and
      homogenized copies of a wide range of milk samples in order to estimate the
      possibility for on-line analysis of the milk. In case of fat content both
      measurement modes resulted in an excellent prediction for homogenized samples
      (R(2)>0.92) but in poor results for raw samples (R(2)<0.70). Homogenization was
      however not mandatory to achieve good predictions for crude protein and lactose
      with both MUATR and HTT, and urea with MUATR spectroscopy. Excellent results were
      obtained for prediction of crude protein, lactose and urea content (R(2)>0.99,
      0.98 and 0.86 respectively) in raw and homogenized milk using MUATR IR
      spectroscopy. These results were significantly better than those obtained by HTT
      IR spectroscopy. However, the prediction performance of HTT was still good for
      crude protein and lactose content (R(2)>0.86 and 0.78 respectively) in raw and
      homogenized samples. However, the detection of urea in milk with HTT spectroscopy
      was significantly better (R(2)=0.69 versus 0.16) after homogenization of the milk
      samples. Based on these observations it can be concluded that MUATR approach is
      most suitable for rapid at line or even on-line milk composition measurement,
      although homogenization is crucial to achieve good prediction of the fat content.

PMID- 21962353
TI  - Classification models for neocryptolepine derivatives as inhibitors of the beta
      haematin formation.
AB  - This paper describes the construction of a QSAR model to relate the structures of
      various derivatives of neocryptolepine to their anti-malarial activities. QSAR
      classification models were build using Linear Discriminant Analysis (LDA),
      Quadratic Discriminant Analysis (QDA), Classification and Regression Trees
      (CART), Partial Least Squares-Discriminant Analysis (PLS-DA), Orthogonal
      Projections to Latent Structures-Discriminant Analysis (OPLS-DA), and Support
      Vector Machines for Classification (SVM-C), using four sets of molecular
      descriptors as explanatory variables. Prior to classification, the molecules were
      divided into a training and a test set using the duplex algorithm. The different
      classification models were compared regarding their predictive ability,
      simplicity, and interpretability. Both binary and multi-class classification
      models were constructed. For classification into three classes, CART and One
      Against-One (OAO)-SVM-C were found to be the best predictive methods, while for
      classification into two classes, LDA, QDA and CART were.

PMID- 21962354
TI  - Quality control of Citri reticulatae pericarpium: exploratory analysis and
      discrimination.
AB  - Extracts of Citri reticulatae pericarpium (PCR) are commonly used in the
      Traditional Chinese Medicine. The quality control of PCR is currently performed
      by single marker analysis, which can hardly describe the complexity of such
      natural samples. In this study, a fingerprint methodology for PCR based on high
      performance liquid chromatography (HPLC) was developed and validated. A total of
      69 fingerprints of authenticated PCR samples, commercial PCR samples, mixed peel
      samples, and other Citrus peels were recorded. Exploratory data analysis allowed
      optimizing the extraction procedure and detecting mixed peel samples. Once the
      optimizations were performed and the method validated, discrimination between the
      authentic PCR samples and all other samples was performed by p-Discriminant
      Partial Least Squares. The established model was able to differentiate between
      classes with a high reliability for each sample. Furthermore, evaluation of the
      score and loading plots of the model indicated nobiletin, tangeretin, naringin
      and hesperidin as important markers for the quality control of PCR.

PMID- 21962355
TI  - Opening the kernel of kernel partial least squares and support vector machines.
AB  - Kernel partial least squares (KPLS) and support vector regression (SVR) have
      become popular techniques for regression of complex non-linear data sets. The
      modeling is performed by mapping the data in a higher dimensional feature space
      through the kernel transformation. The disadvantage of such a transformation is,
      however, that information about the contribution of the original variables in the
      regression is lost. In this paper we introduce a method which can retrieve and
      visualize the contribution of the variables to the regression model and the way
      the variables contribute to the regression of complex data sets. The method is
      based on the visualization of trajectories using so-called pseudo samples
      representing the original variables in the data. We test and illustrate the
      proposed method to several synthetic and real benchmark data sets. The results
      show that for linear and non-linear regression models the important variables
      were identified with corresponding linear or non-linear trajectories. The results
      were verified by comparing with ordinary PLS regression and by selecting those
      variables which were indicated as important and rebuilding a model with only
      those variables.

PMID- 21962356
TI  - Frequency self deconvolution in the quantitative analysis of near infrared
      spectra.
AB  - In this paper a new model based on frequency self deconvolution (FSD) is proposed
      for the quantitative analysis of a near infrared (NIR) spectrum. The model
      couples FSD and partial least square regression (PLS). The grid search
      optimization method is used to select the optimal values of the full width at
      half height (FWHH) and the truncation point of the apodization function. The
      proposed FSD-PLS provides a significant improvement in the prediction ability of
      the PLS model. Furthermore, a modification of the new FSD-PLS method is
      introduced to enable the removal of the baseline variations from the NIR spectra.
      The proposed models were validated using absorbance spectra of mixtures composed
      from glucose, urea and triacetin in a phosphate buffer solution where the
      concentrations of the components are selected to be within their physiological
      range in blood. The whole experiments were carried out in a non-controlled
      environment to show that the model can suppress effectively most of the
      experimental variations. The results show that the standard error of prediction
      (SEP) decreases from 35.58 mg dL(-1) using 8 factors for the PLS model to 15.53
      mg dL(-1) by using 12 factors for the modified FSD-PLS model. The proposed models
      are also shown to yield a slightly improved performance than a newly developed
      second derivative-PLS model without incurring the shortcoming associated with the
      derivative approach in not providing interpretable results and in degrading the
      SNR of the spectra at a faster rate.

PMID- 21962357
TI  - Optimization of pigment dyeing process of high performance fibers using feed
      forward bottleneck neural networks mapping technique.
AB  - Process optimization involves the minimization (or maximization) of an objective
      function, that can be established from a technical and (or) economic viewpoint
      taking into account safety of process. The basic idea of the optimization method
      using neural network (NN) is to replace the model equations (which traditionally
      obtained using, for example, the surface response design or others methods) by an
      equivalent NN. The feed-forward bottleneck neural network (FFBN) as a mapping
      technique is described and evaluated. From the 2D maps the optimal parameters of
      pigment dyeing of high performance fibers on the bases of poly-amide
      benzimidazole (PABI) and polyimide (arimid) are discussed. The studied fibers
      were treated in 32 experiments under the conditions as proposed by the Design of
      Experiment (DOE), varying five influencing factors. Neural network mapping method
      enables visualization of process and shows the influence of different factors on
      different output responses. Optimum parameters were selected upon compromise
      decision.

PMID- 21962358
TI  - Detecting outlying samples in a parallel factor analysis model.
AB  - To explore multi-way data, different methods have been proposed. Here, we study
      the popular PARAFAC (Parallel factor analysis) model, which expresses multi-way
      data in a more compact way, without ignoring the underlying complex structure. To
      estimate the score and loading matrices, an alternating least squares procedure
      is typically used. It is however well known that least squares techniques suffer
      from outlying observations, making the models useless when outliers are present
      in the data. In this paper, we present a robust PARAFAC method. Essentially, it
      searches for an outlier-free subset of the data, on which we can then perform the
      classical PARAFAC algorithm. An outlier map is constructed to identify outliers.
      Simulations and examples show the robustness of our approach.

PMID- 21962360
TI  - Chemometric methods applied to the calibration of a Vis-NIR sensor for gas
      engine's condition monitoring.
AB  - This paper describes the calibration process of a Visible-Near Infrared sensor
      for the condition monitoring of a gas engine's lubricating oil correlating
      transmittance oil spectra with the degradation of a gas engine's oil via a
      regression model. Chemometric techniques were applied to determine different
      parameters: Base Number (BN), Acid Number (AN), insolubles in pentane and
      viscosity at 40  degrees C. A Visible-Near Infrared (400-1100 nm) sensor
      developed in Tekniker research center was used to obtain the spectra of
      artificial and real gas engine oils. In order to improve sensor's data, different
      preprocessing methods such as smoothing by Saviztky-Golay, moving average with
      Multivariate Scatter Correction or Standard Normal Variate to eliminate the
      scatter effect were applied. A combination of these preprocessing methods was
      applied to each parameter. The regression models were developed by Partial Least
      Squares Regression (PLSR). In the end, it was shown that only some models were
      valid, fulfilling a set of quality requirements. The paper shows which models
      achieved the established validation requirements and which preprocessing methods
      perform better. A discussion follows regarding the potential improvement in the
      robustness of the models.

PMID- 21962359
TI  - Linear and nonlinear quantitative structure-activity relationship modeling of the
      HIV-1 reverse transcriptase inhibiting activities of thiocarbamates.
AB  - For a series of thiocarbamates, non-nucleoside HIV-1 reverse transcriptase
      inhibitors, few descriptors have been selected from a large pool of theoretical
      molecular descriptors by means of the ant colony optimization (ACO) feature
      selection method. The selected descriptors were correlated with the bioactivities
      of the molecules using the well known multiple linear regression (MLR) and
      partial least squares (PLS) regression techniques, and, to account for
      nonlinearity, also PLS coupled to radial basis function (RBF) on the one hand and
      radial basis function neural network (RBFNN) on the other. In this case study,
      the RBF/PLS results were better than those from the other modeling techniques
      applied. The prediction ability of the ACO/RBF/PLS-based quantitative structure
      activity relationship (QSAR) model was found to be significantly superior to
      comparative molecular field analysis (CoMFA) and comparative molecular similarity
      index analysis (CoMSIA) models previously established for this series of
      compounds. It was also demonstrated that RBF as a nonlinear approach is useful in
      deriving simple and predictive QSAR models, without the need to recourse to
      expeditious 3D methodologies.

PMID- 21962361
TI  - Resolution and segmentation of hyperspectral biomedical images by multivariate
      curve resolution-alternating least squares.
AB  - MCR-ALS is a resolution method that has been applied in many different fields,
      such as process analysis, environmental data and, recently, hyperspectral image
      analysis. In this context, the algorithm provides the distribution maps and the
      pure spectra of the image constituents from the sole information in the raw image
      measurement. Based on the distribution maps and spectra obtained, additional
      information can be easily derived, such as identification of constituents when
      libraries are available or quantitation within the image, expressed as
      constituent signal contribution. This work summarizes first the protocol followed
      for the resolution on two examples of kidney calculi, taken as representations of
      images with major and minor compounds, respectively. Image segmentation allows
      separating regions of images according to their pixel similarity and is also
      relevant in the biomedical field to differentiate healthy from non-healthy
      regions in tissues or to identify sample regions with distinct properties.
      Information on pixel similarity is enclosed not only in pixel spectra, but also
      in other smaller pixel representations, such as PCA scores. In this paper, we
      propose the use of MCR scores (concentration profiles) for segmentation purposes.
      K-means results obtained from different pixel representations of the data set are
      compared. The main advantages of the use of MCR scores are the interpretability
      of the class centroids and the compound-wise selection and preprocessing of the
      input information in the segmentation scheme.

PMID- 21962362
TI  - Evaluating the reliability of analytical results using a probability criterion: a
      Bayesian perspective.
AB  - Methods validation is mandatory in order to assess the fitness of purpose of the
      developed analytical method. Of core importance at the end of the validation is
      the evaluation of the reliability of the individual results that will be
      generated during the routine application of the method. Regulatory guidelines
      provide a general framework to assess the validity of a method, but none address
      the issue of results reliability. In this study, a Bayesian approach is proposed
      to address this concern. Results reliability is defined here as "the probability
      (pi) of an analytical method to provide analytical results (X) within predefined
      acceptance limits (+/-lambda) around their reference or conventional true
      concentration values (MU(T)) over a defined concentration range and under given
      environmental and operating conditions." By providing the minimum reliability
      probability (pi(min)) needed for the subsequent routine application of the
      method, as well as specifications or acceptance limits (+/-lambda), the proposed
      Bayesian approach provides the effective probability of obtaining reliable future
      analytical results over the whole concentration range investigated. This is
      summarised in a single graph: the reliability profile. This Bayesian reliability
      profile is also compared to two frequentist approaches, the first one derived
      from the work of Dewe et al. [W. Dewe, B. Govaerts, B. Boulanger, E. Rozet, P.
      Chiap, Ph. Hubert, Chemometr. Intell. Lab. Syst. 85 (2007) 262-268] and the
      second proposed by Govaerts et al. [B. Govaerts, W. Dewe, M. Maumy, B. Boulanger,
      Qual. Reliab. Eng. Int. 24 (2008) 667-680]. Furthermore, to illustrate the
      applicability of the Bayesian reliability profile, this approach is also applied
      here to a bioanalytical method dedicated to the determination of ketoglutaric
      acid (KG) and hydroxymethylfurfural (HMF) in human plasma by SPE-HPLC-UV.

PMID- 21962363
TI  - Information-theoretical feature selection using data obtained by scanning
      electron microscopy coupled with and energy dispersive X-ray spectrometer for the
      classification of glass traces.
AB  - In this work, a selection of the best features for multivariate forensic glass
      classification using Scanning Electron Microscopy coupled with an Energy
      Dispersive X-ray spectrometer (SEM-EDX) has been performed. This has been
      motivated by the fact that the databases available for forensic glass
      classification are sparse nowadays, and the acquisition of SEM-EDX data is both
      costly and time-consuming for forensic laboratories. The database used for this
      work consists of 278 glass objects for which 7 variables, based on their
      elemental compositions obtained with SEM-EDX, are available. Two categories are
      considered for the classification task, namely containers and car/building
      windows, both of them typical in forensic casework. A multivariate model is
      proposed for the computation of the likelihood ratios. The feature selection
      process is carried out by means of an exhaustive search, with an Empirical Cross
      Entropy (ECE) objective function. The ECE metric takes into account not only the
      discriminating power of the model in use, but also its calibration, which
      indicates whether or not the likelihood ratios are interpretable in a
      probabilistic way. Thus, the proposed model is applied to all the 63 possible
      univariate, bivariate and trivariate combinations taken from the 7 variables in
      the database, and its performance is ranked by its ECE. Results show remarkable
      accuracy of the best variables selected following the proposed procedure for the
      task of classifying glass fragments into windows (from cars or buildings) or
      containers, obtaining high (almost perfect) discriminating power and good
      calibration. This allows the proposed models to be used in casework. We also
      present an in-depth analysis which reveals the benefits of the proposed ECE
      metric as an assessment tool for classification models based on likelihood
      ratios.

PMID- 21962364
TI  - Deconvolution of pulse trains with the L0 penalty.
AB  - The output of many instruments can be modeled as a convolution of an impulse
      response and a series of sharp spikes. Deconvolution considers the inverse
      problem: estimate the input spike train from an observed (noisy) output signal.
      We approach this task as a linear inverse problem, solved using penalized
      regression. We propose the use of an L(0) penalty and compare it with the more
      common L(2) and L(1) penalties. In all cases a simple and iterative weighted
      regression procedure can be used. The model is extended with a smooth component
      to handle drifting baselines. Application to three different data sets shows
      excellent results.

PMID- 21962365
TI  - Characterisation of heavy oils using near-infrared spectroscopy: optimisation of
      pre-processing methods and variable selection.
AB  - In this study, chemometric predictive models were developed from near infrared
      (NIR) spectra for the quantitative determination of saturates, aromatics, resins
      and asphaltens (SARA) in heavy petroleum products. Model optimisation was based
      on adequate pre-processing and/or variable selection. In addition to classical
      methods, the potential of a genetic algorithm (GA) optimisation, which allows the
      co-optimisation of pre-processing methods and variable selection, was evaluated.
      The prediction results obtained with the different models were compared and
      decision regarding their statistical significance was taken applying a
      randomization t-test. Finally, the results obtained for the root mean square
      errors of prediction (and the corresponding concentration range) expressed in
      %(w/w), are 1.51 (14.1-99.1) for saturates, 1.59 (0.7-61.1) for aromatics, 0.77
      (0-34.5) for resins and 1.26 (0-14.7) for asphaltens. In addition, the usefulness
      of the proposed optimisation method for global interpretation is shown, in
      accordance with the known chemical composition of SARA fractions.

PMID- 21962366
TI  - Characterization of activated sludge abnormalities by image analysis and
      chemometric techniques.
AB  - This work focuses on the use of chemometric techniques for identifying activated
      sludge process abnormalities. Chemometric methods combined with image analysis
      can improve activated sludge systems monitoring and minimize the need of
      analytical measurements. For that purpose data was collected from aggregated and
      filamentous biomass, biomass composition on Gram-positive/Gram-negative bacteria
      and viable/damaged bacteria, and operational parameters. Principal component
      analysis (PCA) was subsequently applied to identify activated sludge
      abnormalities, allowing the identification of several disturbances, namely
      filamentous bulking, pinpoint flocs formation, and zoogleal bulking as well as
      normal conditions by grouping the collected samples in corresponding clusters.

PMID- 21962367
TI  - Modelling spatial and temporal variations in the water quality of an artificial
      water reservoir in the semiarid midwest of Argentina.
AB  - Temporal and spatial patterns of water quality of an important artificial water
      reservoir located in the semiarid Midwest of Argentina were investigated using
      chemometric techniques. Surface water samples were collected at 38 points of the
      water reservoir during eleven sampling campaigns between October 1998 and June
      2000, covering the warm wet season and the cold dry season, and analyzed for
      dissolved oxygen (DO), conductivity, pH, ammonium, nitrate, nitrite, total
      dissolved solids (TDS), alkalinity, hardness, bicarbonate, chloride, sulfate,
      calcium, magnesium, fluoride, sodium, potassium, iron, aluminum, silica,
      phosphate, sulfide, arsenic, chromium, lead, cadmium, chemical oxygen demand
      (COD), biochemical oxygen demand (BOD), viable aerobic bacteria (VAB) and total
      coliform bacteria (TC). Concentrations of lead, ammonium, nitrite and coliforms
      were higher than the maximum allowable limits for drinking water in a large
      proportion of the water samples. To obtain a general representation of the
      spatial and temporal trends of the water quality parameters at the reservoir, the
      three-dimensional dataset (sampling sites*parameters*sampling campaigns) has been
      analyzed by matrix augmentation principal component analysis (MA-PCA) and N-way
      principal component analysis (N-PCA) using Tucker3 and PARAFAC (Parallel Factor
      Analysis) models. MA-PCA produced a component accounting for the general behavior
      of parameters associated with organic pollution. The Tucker3 models were not
      appropriate for modelling the water quality dataset. The two-factor PARAFAC model
      provided the best picture to understand the spatial and temporal variation of the
      water quality parameters of the reservoir. The first PARAFAC factor contains
      useful information regarding the relation of organic pollution with seasonality,
      whereas the second factor also encloses information concerning lead pollution.
      The most polluted areas in the reservoir and the polluting sources were
      identified by plotting PARAFAC loadings as a function of the UTM (Universal
      Transverse Mercator) coordinates.

PMID- 21962368
TI  - Investigation of interpolation techniques for the reconstruction of the first
      dimension of comprehensive two-dimensional liquid chromatography-diode array
      detector data.
AB  - Simulated and experimental data were used to measure the effectiveness of common
      interpolation techniques during chromatographic alignment of comprehensive two
      dimensional liquid chromatography-diode array detector (LC*LC-DAD) data.
      Interpolation was used to generate a sufficient number of data points in the
      sampled first chromatographic dimension to allow for alignment of retention times
      from different injections. Five different interpolation methods, linear
      interpolation followed by cross correlation, piecewise cubic Hermite
      interpolating polynomial, cubic spline, Fourier zero-filling, and Gaussian
      fitting, were investigated. The fully aligned chromatograms, in both the first
      and second chromatographic dimensions, were analyzed by parallel factor analysis
      to determine the relative area for each peak in each injection. A calibration
      curve was generated for the simulated data set. The standard error of prediction
      and percent relative standard deviation were calculated for the simulated peak
      for each technique. The Gaussian fitting interpolation technique resulted in the
      lowest standard error of prediction and average relative standard deviation for
      the simulated data. However, upon applying the interpolation techniques to the
      experimental data, most of the interpolation methods were not found to produce
      statistically different relative peak areas from each other. While most of the
      techniques were not statistically different, the performance was improved
      relative to the PARAFAC results obtained when analyzing the unaligned data.

PMID- 21962370
TI  - Time series hyperspectral chemical imaging data: challenges, solutions and
      applications.
AB  - Hyperspectral chemical imaging (HCI) integrates imaging and spectroscopy
      resulting in three-dimensional data structures, hypercubes, with two spatial and
      one wavelength dimension. Each spatial image pixel in a hypercube contains a
      spectrum with >100 datapoints. While HCI facilitates enhanced monitoring of multi
      component systems; time series HCI offers the possibility of a more comprehensive
      understanding of the dynamics of such systems and processes. This implies a need
      for modeling strategies that can cope with the large multivariate data structures
      generated in time series HCI experiments. The challenges posed by such data
      include dimensionality reduction, temporal morphological variation of samples and
      instrumental drift. This article presents potential solutions to these
      challenges, including multiway analysis, object tracking, multivariate curve
      resolution and non-linear regression. Several real world examples of time series
      HCI data are presented to illustrate the proposed solutions.

PMID- 21962369
TI  - Decision trees in selection of featured determined food quality.
AB  - The determination of food quality, authenticity and the detection of
      adulterations are problems of increasing importance in food chemistry. Recently,
      chemometric classification techniques and pattern recognition analysis methods
      for wine and other alcoholic beverages have received great attention and have
      been largely used. Beer is a complex mixture of components: on one hand a
      volatile fraction, which is responsible for its aroma, and on the other hand, a
      non-volatile fraction or extract consisting of a great variety of substances with
      distinct characteristics. The aim of this study was to consider parameters which
      contribute to beer differentiation according to the quality grade. Chemical (e.g.
      pH, acidity, dry extract, alcohol content, CO(2) content) and sensory features
      (e.g. bitter taste, color) were determined in 70 beer samples and used as
      variables in decision tree techniques. This pattern recognition techniques
      applied to the dataset were able to extract information useful in obtaining a
      satisfactory classification of beer samples according to their quality grade.
      Feature selection procedures indicated which features are the most discriminating
      for classification.

PMID- 21962371
TI  - Application of artificial neural network in food classification.
AB  - Artificial neural network (ANN) classifiers have been successfully implemented
      for various quality inspection and grading tasks of diverse food products. ANN
      are very good pattern classifiers because of their ability to learn patterns that
      are not linearly separable and concepts dealing with uncertainty, noise and
      random events. In this research, the ANN was used to build the classification
      model based on the relevant features of beer. Samples of the same brand of beer
      but with varying manufacturing dates, originating from miscellaneous
      manufacturing lots, have been represented in the multidimensional space by data
      vectors, which was an assembly of 12 features (% of alcohol, pH, % of CO(2)
      etc.). The classification has been performed for two subsets, the first that
      included samples of good quality beer and the other containing samples of
      unsatisfactory quality. ANN techniques allowed the discrimination between
      qualities of beer samples with up to 100% of correct classifications.

PMID- 21962372
TI  - Improved variable reduction in partial least squares modelling based on
      predictive-property-ranked variables and adaptation of partial least squares
      complexity.
AB  - The calibration performance of partial least squares for one response variable
      (PLS1) can be improved by elimination of uninformative variables. Many methods
      are based on so-called predictive variable properties, which are functions of
      various PLS-model parameters, and which may change during the variable reduction
      process. In these methods variable reduction is made on the variables ranked in
      descending order for a given variable property. The methods start with full
      spectrum modelling. Iteratively, until a specified number of remaining variables
      is reached, the variable with the smallest property value is eliminated; a new
      PLS model is calculated, followed by a renewed ranking of the variables. The
      Stepwise Variable Reduction methods using Predictive-Property-Ranked Variables
      are denoted as SVR-PPRV. In the existing SVR-PPRV methods the PLS model
      complexity is kept constant during the variable reduction process. In this study,
      three new SVR-PPRV methods are proposed, in which a possibility for decreasing
      the PLS model complexity during the variable reduction process is build in.
      Therefore we denote our methods as PPRVR-CAM methods (Predictive-Property-Ranked
      Variable Reduction with Complexity Adapted Models). The selective and predictive
      abilities of the new methods are investigated and tested, using the absolute PLS
      regression coefficients as predictive property. They were compared with two
      modifications of existing SVR-PPRV methods (with constant PLS model complexity)
      and with two reference methods: uninformative variable elimination followed by
      either a genetic algorithm for PLS (UVE-GA-PLS) or an interval PLS (UVE-iPLS).
      The performance of the methods is investigated in conjunction with two data sets
      from near-infrared sources (NIR) and one simulated set. The selective and
      predictive performances of the variable reduction methods are compared
      statistically using the Wilcoxon signed rank test. The three newly developed
      PPRVR-CAM methods were able to retain significantly smaller numbers of
      informative variables than the existing SVR-PPRV, UVE-GA-PLS and UVE-iPLS methods
      without loss of prediction ability. Contrary to UVE-GA-PLS and UVE-iPLS, there is
      no variability in the number of retained variables in each PPRV(R) method.
      Renewed variable ranking, after deletion of a variable, followed by remodelling,
      combined with the possibility to decrease the PLS model complexity, is
      beneficial. A preferred PPRVR-CAM method is proposed.

PMID- 21962373
TI  - Diprotonation process of meso-tetraphenylporphyrin derivatives designed for
      photodynamic therapy of cancers: from multivariate curve resolution to predictive
      QSPR modeling.
AB  - Tetrapyrrole rings possess four nitrogen atoms, two of which act as Brondsted
      bases in acidic media. The two protonation steps occur on a close pH range,
      particularly in the case of meso-tetraphenylporphyrin (TPP) derivatives. If the
      cause of this phenomenon is well known--a protonation-induced distortion of the
      porphyrin ring--data on stepwise protonation constants and on electronic
      absorption spectra of monoprotonated TPPs are sparse. A multivariate approach has
      been systematically applied to a series of glycoconjugated and hydroxylated TPPs,
      potential anticancer drugs usable in Photodynamic Therapy. The dual purpose was
      determination of protonation constants and linking substitution with basicity.
      Hard-modeling version of MCR-ALS (Multivariate Curve Resolution Alternating Least
      Squares) has given access to spectra and distribution profile of pure components.
      Spectra of monoprotonated species (H(3)TPP(+)) in solution resemble those of
      diprotonated species (H(4)TPP(2+)), mainly differing by a slight blue-shift of
      bands. Overlap of H(3)TPP(+) and H(4)TPP(2+) spectra reinforces the difficulty to
      evidence an intermediate form only present in low relative abundance. Depending
      on macrocycle substitution, pK values ranged from 3.5+/-0.1 to 5.1+/-0.1 for the
      first protonation and from 3.2+/-0.2 to 4.9+/-0.1 for the second one. Inner
      nitrogens' basicity is affected by position, number and nature of peripheral
      substituents depending on their electrodonating character. pK values have been
      used to establish a predictive Multiple Linear Regression (MLR) model, relying on
      atom-type electrotopological indices. This model accurately describes our results
      and should be applied to new TPP derivatives in a drug-design perspective.

PMID- 21962374
TI  - Optimization of gradient profiles in ion-exchange chromatography using computer
      simulation programs.
AB  - Optimization procedure of gradient separations in ion-exchange chromatography
      using simplex optimization method in combination with the computer simulation
      program for ion-exchange chromatography is presented. The optimization of
      parameters describing gradient profile for the separation in ion chromatography
      is based on the optimization criterion obtained from calculated chromatograms.
      The optimization criterion depends on the parameters used for calculations and
      thus exhibits the quality of gradient conditions for the separation of the
      analytes. Simplex method is used to calculate new gradient profiles in order to
      reach optimum separations for the selected set of analytes. The Simplex algorithm
      works stepwise, for each new combination of parameters that describe the gradient
      profile a new calculation is performed and from the calculated chromatogram the
      optimization criterion is determined. The proposed method is efficient and may
      reduce the time and cost of analyses of complex samples with ion-exchange
      chromatography.

PMID- 21962375
TI  - Experimental determination and prediction of bilitranslocase transport activity.
AB  - The transport activity of a membrane protein, bilitranslocase (T.C. #
      2.A.65.1.1), which acts as a transporter of bilirubin from blood to liver cells,
      was experimentally determined for a large set of various endogenous compounds,
      drugs, purine and pyrimidine derivatives. On these grounds, the structure
      activity models were developed following the OECD principles of QSAR models and
      their predictive ability for new chemicals was evaluated. The applicability
      domain of the models was estimated by Euclidean distances criteria according to
      the applied modeling method. The selection of the most influential structural
      variables was an important stage in the adopted modeling methodology. The
      interpretation of selected variables was performed in order to get an insight
      into the mechanism of transport through the cell membrane via bilitranslocase.
      Validation of the optimized models was performed by a previously determined
      validation set. The classification model was build to separate active from
      inactive compounds. The resulting accuracy, sensitivity, and specificity were
      0.73, 0.89, and 0.64, respectively. Only active compounds were used to develop a
      predictive model for bilitranslocase inhibition constants. The model showed good
      predictive ability; Root Mean Squared error of the validation set, RMS(V)=0.29
      log units.

PMID- 21962376
TI  - Detection and chemical profiling of medicine counterfeits by Raman spectroscopy
      and chemometrics.
AB  - Raman spectroscopy combined with chemometrics has recently become a widespread
      technique for the analysis of pharmaceutical solid forms. The application
      presented in this paper is the investigation of counterfeit medicines. This
      increasingly serious issue involves networks that are an integral part of
      industrialized organized crime. Efficient analytical tools are consequently
      required to fight against it. Quick and reliable authentication means are needed
      to allow the deployment of measures from the company and the authorities. For
      this purpose a method in two steps has been implemented here. The first step
      enables the identification of pharmaceutical tablets and capsules and the
      detection of their counterfeits. A nonlinear classification method, the Support
      Vector Machines (SVM), is computed together with a correlation with the database
      and the detection of Active Pharmaceutical Ingredient (API) peaks in the suspect
      product. If a counterfeit is detected, the second step allows its chemical
      profiling among former counterfeits in a forensic intelligence perspective. For
      this second step a classification based on Principal Component Analysis (PCA) and
      correlation distance measurements is applied to the Raman spectra of the
      counterfeits.

PMID- 21962377
TI  - Behavioural consequences of two chronic psychosocial stress paradigms: anxiety
      without depression.
AB  - Chronic stress, in particular chronic psychosocial stress, is a risk factor in
      the aetiology of various psychopathologies including anxiety- and depression
      related disorders. Therefore, recent studies have focussed on the development of
      social-stress paradigms, which are believed to be more relevant to the human
      situation than non-social-stress paradigms. The majority of these paradigms have
      been reported to increase both anxiety- and depression-related behaviour in rats
      or mice. However, in order to dissect the mechanisms underlying anxiety or
      depression, animal models are needed, which specifically induce one, or the
      other, phenotype. Here, we study both short- (1d after stressor termination) and
      long-term (4d or 7d after stressor termination) behavioural and physiological
      consequences of two well-validated chronic psychosocial stress models: social
      defeat/overcrowding (SD/OC) and chronic subordinate colony housing (CSC). We
      demonstrate that SD/OC and CSC result in different physiological alterations:
      SD/OC more strongly affecting body-weight development, whereas CSC more strongly
      affects adrenal and pituitary morphology. Both stressors were shown to flatten
      circadian locomotor activity immediately after stress termination, which
      normalized 7d later in SD/OC group but reversed to hyperactivity during the dark
      phase in the CSC group. Importantly, neither stress paradigm resulted in an
      increase in depression-related behaviour as assessed using the forced swim test,
      tail suspension test and saccharin preference test at any time-point. However,
      both stress paradigms lead to an anxiogenic phenotype; albeit with different
      temporal profiles and not towards a novel con-specific (social anxiety). CSC
      exposure elevates anxiety-related behaviour immediately after stressor
      termination, which lasts for at least 1 wk. In contrast, the anxiogenic phenotype
      only develops 1 wk after SD/OC termination. In conclusion, both models are unique
      for uncovering the molecular underpinnings of anxiety-related behaviour without
      conflicting depression-based alterations.

PMID- 21962379
TI  - Disordered eating behaviour is associated with blunted cortisol and
      cardiovascular reactions to acute psychological stress.
AB  - Research suggests a potential dysregulation of the stress response in individuals
      with bulimia nervosa. This study measured both cardiovascular and cortisol
      reactions to a standardised laboratory stress task in individuals identified as
      showing disordered eating behaviour to determine whether dysregulation of the
      stress response is characteristic of the two branches of the stress response
      system. Female students (N=455) were screened using two validated eating disorder
      questionnaires. Twelve women with disordered eating, including self-induced
      vomiting, and 12 healthy controls were selected for laboratory stress testing.
      Salivary cortisol and cardiovascular activity, via Doppler imaging and semi
      automatic blood pressure monitoring, were measured at resting baseline and during
      and after exposure to a 10-min mental arithmetic stress task. Compared to
      controls the disordered eating group showed blunted cortisol, cardiac output,
      heart rate, and stroke volume reactions to the acute stress, as well as an
      attenuated vasodilatory reaction. These effects could not be accounted for in
      terms of group differences in stress task performance, subjective task
      impact/engagement, age, BMI, neuroticism, cardio-respiratory fitness, or co
      morbid exercise dependence. Our findings suggest that disordered eating is
      characterised by a dysregulation of the autonomic stress-response system. As
      such, they add further weight to the general contention that blunted stress
      reactivity is characteristic of a number of maladaptive behaviours and states.

PMID- 21962378
TI  - Polymorphisms within the metabotropic glutamate receptor 1 gene are associated
      with depression phenotypes.
AB  - OBJECTIVES: Glutamate has been implicated in the pathophysiology and treatment of
      mood disorders possibly by affecting the regulation of the hypothalamus-pituitary
      adrenocortical (HPA) axis. Growing evidence suggests an important role of the
      metabotropic glutamate receptor 1 (mGlu1) in depression-related phenotypes. To
      test whether these findings can also be supported by human genetics data, we
      explored polymorphisms within the metabotropic glutamate receptor 1 gene (GRM1)
      for their association with unipolar depression (UPD) as well as with biological
      phenotypes of this disorder. METHODS: We first tested the association of 43 tag
      SNPs covering the GRM1 locus with UPD in 350 patients and 370 matched controls.
      We then investigated the effects of the associated SNPs on hippocampal glutamate
      levels estimated using 1H-MR-spectroscopy (1H-MRS) and on endocrine measures from
      the combined dexamethasone-suppression/CRH stimulation (dex/CRH) test. RESULTS:
      Within the GRM1 locus, 22 SNPs showed nominally significant association with UPD,
      of which 6 withstood corrections for multiple testing (rs2268666 with best
      allelic p=7.0*10-5). Supportive evidence for an association with UPD was gained
      from a second independent sample with 904 patients and 1012 controls.
      Furthermore, patients homozygous for the non-risk genotypes showed reduced
      hippocampal glutamate levels as measured by 1H-MRS, a more pronounced
      normalization of HPA-axis hyperactivity as well as a better antidepressant
      treatment outcome. CONCLUSIONS: These results suggest that the combination of
      genetic and biological markers may allow to subgroup patients into
      etiopathogenetically more relevant subcategories which could guide clinicians in
      their antidepressant treatment choices.

PMID- 21962380
TI  - Structural and characterization of novel copper(II) azodye complexes.
AB  - The synthetic methods of novel Cu(II) and adduct complexes, with selective
      azodyes containing nitrogen and oxygen donor ligands have been developed,
      characterized and presented. The prepared complexes fall into the stoichiometric
      formulae of [Cu(L(n))(2)](A) and [Cu(L(n))(2)(Py)(2)](B), where two types of
      complexes were expected and described. In type [(A) (1:2)] the chelate rings are
      six-membered/four coordinate, whereas in type [(B) (1:2:2)] they are six
      membered/six coordinate. The important bands in the IR spectra and main (1)H NMR
      signals are tentatively assigned and discussed in relation to the predicted
      assembly of the molecular structure. The IR data of the azodye ligands suggested
      the existing of a bidentate binding involving azodye nitrogen and C-O oxygen atom
      of enolic group. They also showed the presence of Py coordinating with the metal
      ion. The coordination geometries and electronic structures are determined from
      the framework of the proposed modeling of the formed novel complexes. The
      complexes (1-5) exist in trans-isomeric [N,O] solid form, while adduct complexes
      (6-10) exist in trans isomeric (Py) form. The square planar/octahedral
      coordination geometry of Cu(II)/adduct is made up of an N-atom of azodye, the
      deprotonated enolic O-atom and two Py. The azo group was involved in chelation
      for all the prepared complexes. ESR spectra show the simultaneous presence of a
      planar trans and a nearly planar cis isomers in the 1:2 ratio for all N,O
      complexes [Cu(L(n))(2)]. The ligands in the dimmer are stacked over one another.
      In the solid state of azo-rhodanine, the dimmers have inter- and intramolecular
      hydrogen bonds. Interactions between the ligands and Cu(II) are also discussed.

PMID- 21962381
TI  - Experimental and DFT studies on the vibrational and electronic spectra of 4,5
      dihydro-6-methyl-4-[(E)-(3-pyridinylmethylene)amino]-1,2,4-triazin-3(2H)-one.
AB  - Vibrational and electronic spectral measurements were made for 4,5-dihydro-6
      methyl-4-[(E)-(3-pyridinylmethylene)amino]-1,2,4-triazin-3(2H)-one (pymetrozine).
      Optimized geometrical structure and harmonic vibrational frequencies were
      computed by ab initio RHF, B-based DFT methods (BLYP, BP86 and BPW91) and B3
      based DFT methods (B3LYP, B3P86 and B3PW91) using 6-311++G(d,p) basis set.
      Complete assignments of the observed spectra were proposed. The absorption
      spectra of the compound were computed both in gas-phase and in C(2)H(5)OH
      solution using TD-B3LYP/6-311++G(d,p) and PCM-B3LYP/6-311++G(d,p) approaches,
      respectively, the calculated results provide a good description of positions of
      the bands maxima in the observed electronic spectrum. The MEP calculation
      indicates that the most possible site for electrophilic attack is H23 and the
      most possible sites for nucleophilic attack are N5 and O19.

PMID- 21962382
TI  - A multicenter retrospective review of outcomes for arthrodesis, hemi-metallic
      joint implant, and resectional arthroplasty in the surgical treatment of end
      stage hallux rigidus.
AB  - This is a retrospective, multicenter study examining the long-term results for
      the treatment of end-stage hallux rigidus using 3 different surgical procedures.
      A total of 158 subjects (105 females and 53 males) were included in the present
      study. They had undergone 1 of the following surgical procedures: arthrodesis,
      hemi-implant, or resectional arthroplasty. The long-term results for the
      subjective assessment of pain, function, and alignment, as well as objective
      radiographic and physical findings, were examined. The median interval to
      postoperative follow-up for the 3 procedure groups was 159 weeks. No
      statistically significant difference was found in age or the number of subjects
      included in the 3 treatment groups (p = .11 and p = .16, respectively). The body
      mass index was significantly different statistically among the 3 treatment
      groups, with the hemi-implant group representing a smaller body mass index
      compared with the other procedures (p = .007). No statistically significant
      difference was found in the subjective outcomes among the 3 treatment groups
      using the American College of Foot and Ankle Surgeons' First Metatarsophalangeal
      Joint and First Ray Scoring Scale (patient questionnaire) or the modified Hallux
      Metatarsophalangeal-Interphalangeal Scale of the American Orthopedic Foot and
      Ankle Society (p = .64 and p = .14, respectively). Furthermore, the correlation
      coefficient between the 2 subjective scoring scales was 0.78, statistically
      significant and reflecting a moderate to high correlation (p < .001). The results
      of the radiographic and clinical evaluation revealed that metatarsalgia was the
      most common finding for the arthrodesis group (9.8%), bony overgrowth into the
      joint for the hemi-implant group (28.3%), and floating hallux for the resectional
      arthroplasty group (30.9%). The results of our study suggest that all 3 surgical
      procedures are viable options for the treatment of end-stage hallux rigidus.

PMID- 21962383
TI  - An anatomical way of treating ankle syndesmotic injuries.
AB  - Treatment of tibiofibular syndesmotic ankle injury remains controversial in
      regard to the best method, although surgeons agree that the goal of treatment is
      reduction and operative stabilization. Ideally, the implant should stabilize the
      syndesmosis and allow physiologic micromotion and early mobilization, and
      conventional screws are limited in this regard. We reviewed use of the Ankle
      TightRope((r)) fixation device for repair of syndesmotic injuries. From April to
      September 2006, 16 patients with evidence of syndesmotic injury were treated by
      means of ankle fracture open reduction with internal fixation, combined with use
      of the Ankle TightRope((r)) device for repair of the syndesmosis. The mean age of
      the 16 patients was 36.6 +/- 16.71 (range 15 to 69) years; they were followed up
      for at least 2 years. Mean follow-up duration was 26 +/- 3.94 (range 24 to 38)
      months. The mean American Orthopaedic Foot and Ankle Society score at 2-year
      follow-up was 86.88 +/- 11.49 (range 48 to 100). The mean time to full weight
      bearing was 4.5 +/- 0.87 weeks. Two (12.5%) patients had postoperative
      superficial wound infections, each of which was treated with oral antibiotics.
      One (6.25%) patient had the TightRope((r)) removed because of irritation from the
      knot. There was no failure of syndesmotic fixation, despite early weight-bearing
      in the postoperative phase. The results of this case series indicate that
      tibiofibular syndesmosis repair with the Ankle TightRope((r)) yields satisfactory
      results.

PMID- 21962384
TI  - Epidemiogenetic study of French families with Paget's disease of bone.
AB  - OBJECTIVE: To search for association with environmental factors and to determine
      SQSTM1/p62 mutations prevalence in French families with Paget's disease of bone
      (PDB). METHODS: Unrelated patients with a confirmed diagnosis of PDB were
      recruited in three Rheumatology departments and informed consent obtained. First-
      and second-degree relatives of each index case had a physical examination, blood
      taken for DNA extraction and biochemical measurements, and a whole-body bone
      scan. Exons 7 and 8 and exon-intron boundaries of SQSTM1/p62 (p62) gene were PCR
      amplified before sequencing. Haplotype carriers of the p62(P392L) mutation were
      determined. Comparisons between PDB patients and healthy relatives were
      performed. RESULTS: We investigated 18 families consisting of 83 individuals: 20
      patients with known PDB, three relatives with newly-diagnosed PDB and 60 healthy
      relatives. Index cases and/or relatives with Dupuytren's disease were found in
      eight (44.4%) out of the 18 families. Forty-three percent of PDB patients were
      former or current tobacco users versus 18% of healthy relatives (P=0.02; OR=3.37
      (1.04-11.09)). Five index cases (27.8%) were carriers of SQSTM1/p62 mutations:
      three p62(P392L) mutations, one p62(P392L/A390X) double mutation and one
      p62(A390X) mutation. The p62(P392L) mutation was carried by haplotype 2 in all
      four index cases. CONCLUSION: Accurate phenotypic assessment of PDB patients'
      relatives allowed for diagnosing PDB in three asymptomatic relatives. There was
      evidence for an aggregation of Dupuytren's disease in PDB families (not
      associated with SQSTM1/p62 mutation), and for an association between PDB and
      tobacco use. Half of PDB familial forms carried a SQSTM1/p62 mutation, p62(P392L)
      mutation being the most frequent.

PMID- 21962385
TI  - Congenital lumbar spinal stenosis associated with Marfan syndrome.

PMID- 21962386
TI  - The associations between interleukin-1 polymorphisms and susceptibility to
      ankylosing spondylitis: a meta-analysis.
AB  - OBJECTIVE: The aim of this study was to determine whether polymorphisms of
      interleukin-1 (IL-1) confer susceptibility to ankylosing spondylitis (AS).
      METHODS: The authors conducted meta-analyses on associations between IL-1
      polymorphisms and AS susceptibility, using fixed or random effects models. In
      order to avoid duplications and data previously subjected to meta-analysis, we
      performed meta-analysis on studies if new data on IL-1 polymorphisms in AS were
      reported. RESULTS: A total of nine studies consisting of 20 separate comparisons
      of association between IL-1 polymorphisms and AS susceptibility were included in
      this meta-analysis. These were performed on European, Asian, and Latin American
      population samples. Meta-analysis revealed a significant association between the
      2 allele of the IL-1F10.3 polymorphism (rs3811581) and the risk of developing AS
      in Europeans (OR=0.775, 95% CI=0.605-0.992, P=0.043). Furthermore, the OR of the
      2 allele of IL-1A+889 (rs1800587) was found to be significantly increased in
      Europeans with AS (OR=1.357, 95% CI=1.085-1.697, P=0.007). However, meta-analyses
      of the IL-1B-511, IL-1B+3953, and ILF7.1 polymorphisms and of the variable
      numbers of tandem repeats of the IL-1 receptor antagonist gene (IL-1RN VNTR)
      revealed no association between AS and these polymorphisms. CONCLUSIONS: In
      addition to the three known IL-1 polymorphisms, rs2856836, rs17561, and
      rs1894399, found in previous meta-analysis, this meta-analysis shows that the IL
      1F10.3 and IL-1A+889 polymorphisms are associated with the development of AS in
      Europeans but not in Asians.

PMID- 21962387
TI  - Gingival fibroblasts inhibit activity of metalloproteinase: a path toward cell
      therapy?

PMID- 21962388
TI  - Rheumatoid meningitis occurring during adalimumab and methotrexate treatment.
AB  - Rheumatoid arthritis is well known for multiple extra-articular manifestations.
      Here, we present a case of chronic rheumatoid meningitis occurring during
      treatment with methotrexate and the tumour necrosis factor (TNF) alpha antibody
      adalimumab. Nine and seven months, respectively, into the course of these two
      treatments, a 59-year-old Caucasian lady with mild, early, seropositive
      rheumatoid arthritis developed headaches and psychomotor retardation followed by
      seizures. The diagnosis was confirmed by a brain biopsy showing a necrotizing
      granulomatous meningitis. Withdrawal of both drugs and high dose corticosteroids
      led to marked improvement. The addition of the anti-CD20 antibody rituximab
      allowed discontinuation of the corticosteroids. This is the fifth published case
      describing the occurrence of rheumatoid meningitis during treatment with TNF
      blockers. TNF blockers and methotrexate thus do not appear to prevent this
      complication, and may even contribute to its development.

PMID- 21962389
TI  - Psoriatic arthritis in two patients with an inadequate response to treatment with
      tocilizumab.
AB  - Psoriatic arthritis (PsA) is considered as one of the seronegative
      spondylarthropathies. Like rheumatoid arthritis (RA), the increased production of
      interleukin (IL)-6 suggests a pathogenic role of IL-6 in PsA. However, whether
      humanized anti-IL-6 receptor antibody such as tocilizumab (TCZ) might be
      effective for PsA as well as RA has yet to be determined. We report herein two
      cases of PsA treated using TCZ. Although, TCZ treatment resulted in disappearance
      of serum CRP in both patients, arthritis and skin lesions were not improved
      despite 6-month administration of TCZ. In contrast, tumor necrosis factor (TNF)
      inhibitor proved effective against arthritis and skin lesions in these patients.
      Collectively, these findings not only indicate that IL-6 has distinct
      pathological roles in RA and PsA, but also suggest that TNF inhibitor therapy
      (but not TCZ) is effective for arthritis and skin lesions of PsA.

PMID- 21962390
TI  - Systemic lupus erythematosus and celiac disease.

PMID- 21962391
TI  - Isolation and characterization of antimicrobial food components.
AB  - Nowadays there is an evident growing interest in natural antimicrobial compounds
      isolated from food matrices. According to the type of matrix, different isolation
      and purification steps are needed and as these active compounds belong to
      different chemical classes, also different chromatographic and electrophoretic
      methods coupled with various detectors (the most used diode array detector and
      mass spectrometer) have to be performed. This review covers recent steps made in
      the fundamental understanding of sample preparation methods as well as of
      analytical tools useful for the complete characterization of bioactive food
      compounds. The most commonly used methods for extraction of natural antimicrobial
      compounds are the conventional liquid-liquid or solid-liquid extraction and the
      modern techniques such as pressurized liquid extraction, microwave-assisted
      extraction, ultrasound-assisted extraction, solid-phase micro-extraction,
      supercritical fluid extraction, and matrix solid phase dispersion. The complete
      characterization of the compounds is achieved using both monodimensional
      chromatographic processes (LC, nano-LC, GC, and CE coupled with different type of
      detectors) and, recently, using comprehensive two-dimensional systems (LC*LC and
      GC*GC).

PMID- 21962392
TI  - Is there a future for auto-allo HSCT in multiple myeloma?

PMID- 21962394
TI  - Psychometric properties and construct validity of the Muscle Appearance
      Satisfaction Scale among Hungarian men.
AB  - Limited studies have evaluated the psychometric properties of the Muscle
      Appearance Satisfaction Scale (MASS), a measure of muscle dysmorphia, in
      different cultures and languages. The aims were to examine the psychometric
      properties of the Hungarian version of the MASS (MASS-HU), and to investigate its
      relationship with self-esteem and exercise-related variables. Two independent
      samples of male weight lifters (ns=289 and 43), and a sample of undergraduates
      (n=240) completed the MASS, Eating Disorder Inventory, and Rosenberg Self-esteem
      Scale. Exploratory factor analysis supported the original five-factor structure
      of the MASS only in the weight lifter sample. The MASS-HU had excellent scale
      score reliability and good test-retest reliability. The construct validity of the
      MASS-HU was tested with multivariate regression analyses which indicated an
      inverse relationship between self-esteem and muscle dysmorphia. The 18-item MASS
      HU was found to be a useful measure for the assessment of muscle dysmorphia among
      male weight lifters.

PMID- 21962393
TI  - Autologous haemopoietic stem-cell transplantation followed by allogeneic or
      autologous haemopoietic stem-cell transplantation in patients with multiple
      myeloma (BMT CTN 0102): a phase 3 biological assignment trial.
AB  - BACKGROUND: Autologous haemopoietic stem-cell transplantation (HSCT) improves
      survival in patients with multiple myeloma, but disease progression remains an
      issue. Allogeneic HSCT might reduce disease progression, but can be associated
      with high treatment-related mortality. Thus, we aimed to assess effectiveness of
      allogeneic HSCT with non-myeloablative conditioning after autologous HSCT
      compared with tandem autologous HSCT. METHODS: In our phase 3 biological
      assignment trial, we enrolled patients with multiple myeloma attending 37
      transplant centres in the USA. Patients (<70 years old) with adequate organ
      function who had completed at least three cycles of systemic antimyeloma therapy
      within the past 10 months were eligible for inclusion. We assigned patients to
      receive an autologous HSCT followed by an allogeneic HSCT (auto-allo group) or
      tandem autologous HSCTs (auto-auto group) on the basis of the availability of an
      HLA-matched sibling donor. Patients in the auto-auto group subsequently underwent
      a random allocation (1:1) to maintenance therapy (thalidomide plus dexamethasone)
      or observation. To avoid enrolment bias, we classified patients as standard risk
      or high risk on the basis of cytogenetics and beta2-microglobulin concentrations.
      We used the Kaplan-Meier method to estimate differences in 3-year progression
      free survival (PFS; primary endpoint) between patients with standard-risk disease
      in the auto-allo group and the best results from the auto-auto group
      (maintenance, observation, or pooled). This study is registered with
      ClinicalTrials.gov, number NCT00075829. FINDINGS: Between Dec 17, 2003, and March
      30, 2007, we enrolled 710 patients, of whom 625 had standard-risk disease and
      received an autologous HSCT. 156 (83%) of 189 patients with standard-risk disease
      in the auto-allo group and 366 (84%) of 436 in the auto-auto group received a
      second transplant. 219 patients in the auto-auto group were randomly assigned to
      observation and 217 to receive maintenance treatment, of whom 168 (77%) completed
      this treatment. PFS and overall survival did not differ between maintenance and
      observation groups and pooled data were used. Kaplan-Meier estimates of 3-year
      PFS were 43% (95% CI 36-51) in the auto-allo group and 46% (42-51) in the auto
      auto group (p=0.671); overall survival also did not differ at 3 years (77% [95%
      CI 72-84] vs 80% [77-84]; p=0.191). Within 3 years, 87 (46%) of 189 patients in
      the auto-allo group had grade 3-5 adverse events as did 185 (42%) of 436 patients
      in the auto-auto group. The adverse events that differed most between groups were
      hyperbilirubinaemia (21 [11%] patients in the auto-allo group vs 14 [3%] in the
      auto-auto group) and peripheral neuropathy (11 [6%] in the auto-allo group vs 52
      [12%] in the auto-auto group). INTERPRETATION: Non-myeloablative allogeneic HSCT
      after autologous HSCT is not more effective than tandem autologous HSCT for
      patients with standard-risk multiple myeloma. Further enhancement of the graft
      versus myeloma effect and reduction in transplant-related mortality are needed to
      improve the allogeneic HSCT approach. FUNDING: US National Heart, Lung, and Blood
      Institute and the National Cancer Institute.

PMID- 21962395
TI  - Real-time stylistic prediction for whole-body human motions.
AB  - The ability to predict human motion is crucial in several contexts such as human
      tracking by computer vision and the synthesis of human-like computer graphics.
      Previous work has focused on off-line processes with well-segmented data;
      however, many applications such as robotics require real-time control with
      efficient computation. In this paper, we propose a novel approach called real
      time stylistic prediction for whole-body human motions to satisfy these
      requirements. This approach uses a novel generative model to represent a whole
      body human motion including rhythmic motion (e.g., walking) and discrete motion
      (e.g., jumping). The generative model is composed of a low-dimensional state
      (phase) dynamics and a two-factor observation model, allowing it to capture the
      diversity of motion styles in humans. A real-time adaptation algorithm was
      derived to estimate both state variables and style parameter of the model from
      non-stationary unlabeled sequential observations. Moreover, with a simple
      modification, the algorithm allows real-time adaptation even from incomplete
      (partial) observations. Based on the estimated state and style, a future motion
      sequence can be accurately predicted. In our implementation, it takes less than
      15 ms for both adaptation and prediction at each observation. Our real-time
      stylistic prediction was evaluated for human walking, running, and jumping
      behaviors.

PMID- 21962396
TI  - The structure and stability of temperament from infancy to toddlerhood: a one
      year prospective study.
AB  - This study investigated the factor structure and longitudinal stability of
      temperament in a multi-informant (i.e., as reported by mothers and fathers), one
      year prospective study from infancy (8-13 months) to toddlerhood (20-25 months).
      Confirmatory factor analyses (CFAs) replicate and extend earlier studies; in that
      evidence was found for a three-factor structure for both infant and toddler
      temperament, consisting of Surgency/Extraversion, Negative Affectivity and
      Effortful Control. There were, especially in toddlerhood, few differences between
      mother and father reports in average scores on the three temperament factors,
      which were in part related to differences in parental involvement between mothers
      and fathers. In addition, there were few differences between average scores for
      boys and girls on these temperament factors, with the exception that both mothers
      and fathers rated girls higher on Effortful Control, and fathers rated boys
      higher on Extraversion/Surgency, especially in toddlerhood. Finally, results
      showed that the three factors showed high relative, absolute, and structural
      stability over a one-year period. The implications of these findings for
      contemporary temperament research are discussed.

PMID- 21962397
TI  - [Association between adiposity and cardiovascular risk factors in prepubertal
      children].
AB  - INTRODUCTION AND OBJECTIVES: To examine the relationships between of four
      measures of adiposity, namely waist circumference (WC), body mass index (BMI),
      and subscapular and abdominal skinfolds, with different cardiovascular risk
      factors in prepubertal children. METHODS: Four hundred and ninety-four
      prepubertal children aged 6-10 years participated in this cross-sectional study.
      The subscapular and abdominal skinfolds, WC, and BMI were measured to assess
      adiposity, and cardiovascular risk factors (CVRFs) were assessed by measuring
      systolic (SBP) and diastolic blood pressures (DBP), glucose, triglycerides (TG),
      and high density (HDL-C) and low density lipoprotein cholesterol (LDL-C).
      Dichotomous variables were created based on whether or not the subjects were in
      the upper quartile (Q4) for the WC, BMI, and skinfold variables. RESULTS: No CVRF
      was found in 52.8% of children, 33.4% had one factor, and 10.9% and 2.8% had 2
      and 3 factors respectively. An adjusted logistic regression analysis showed that
      being in Q4 of anthropometric variables and CVRFs was associated to TG levels >=
      100 mg/dL. Glucose levels >= 96 mg/dL were associated to Q4 and abdominal fold.
      Presence of 2 or more CVRFs was significantly associated to Q4 in all
      anthropometric variables despite adjustment for age, gender, and calorie intake.
      The subscapular skinfold was the adiposity marker associated to the highest risk.
      CONCLUSIONS: Children with a more unfavorable adiposity profile tend to have a
      greater cardiovascular risk in the prepubertal stage.

PMID- 21962398
TI  - Acute lithium administration selectively lowers tyrosine levels in serum and
      brain.
AB  - Lithium exerts anti-dopaminergic behavioral effects. We examined whether some of
      these might be mediated by changes in brain levels of tyrosine (TYR), the
      precursor to dopamine. Lithium chloride (LiCl(2)) 3.0mEq/kg IP acutely lowered
      serum TYR and the ratio of serum TYR to other large neutral amino acids (LNAAs);
      it also selectively lowered striatum TYR levels as measured in tissue or in vivo.
      While LiCl(2) 3.0mEq/kg IP also augmented haloperidol (0.19mg/kg SC)-induced
      catalepsy, this lithium effect was not attenuated by administration of TYR
      100mg/kg IP. We conclude that lithium acutely and selectively lowers brain TYR by
      lowering serum levels of tyrosine relative to the LNAAs that compete with it for
      transport across the blood-brain barrier. However, the lowering of TYR does not
      appear to significantly contribute to the ability of lithium to potentiate
      haloperidol-mediated catalepsy.

PMID- 21962399
TI  - Circulating antioxidant profile of pregnant women with asthma.
AB  - BACKGROUND & AIMS: One of the most prevalent complications of pregnancy is asthma
      which is associated with an increased incidence of intrauterine growth
      restriction. The mechanisms that affect fetal development in pregnancies
      complicated by asthma are not clearly defined. Antioxidants are particularly
      important during pregnancy due to their protective role against a state of high
      oxidative stress as gestation progresses. The current study was designed to
      characterise the circulating profile of tocopherols and carotenoids in pregnant
      women with asthma to determine whether asthma severity and dietary intake were
      associated with an altered antioxidant profile. METHODS: Maternal dietary intake
      and plasma and erythrocyte concentrations of tocopherols and carotenoids were
      examined in women with (n = 84) and without asthma (n = 47) at 18, 30 and 36
      weeks gestation. Tocopherol and carotenoid levels were related to fetal and birth
      outcomes. RESULTS: Pregnant women with moderate/severe asthma were found to have
      increased plasma concentrations of total carotenoids (P < 0.05), lutein (P < 0.05
      and alpha-tocopherol (P < 0.02) late in gestation compared to those women with
      mild asthma and healthy pregnant controls. Moderate/severe asthmatics had higher
      erythrocyte alpha-tocopherol quinone levels early in gestation relative to the
      controls (P < 0.02) but this marker of oxidative stress decreased as gestation
      progressed. Tocopherols and carotenoids were positively associated with birth
      weight centile (P < 0.05). CONCLUSION: These findings suggest that the maternal
      system adjusts antioxidant pathways in response to the presence of a high
      oxidative load induced by asthma during pregnancy in an attempt to ensure
      continued fetal growth in an adverse environment.

PMID- 21962400
TI  - The role of operative intervention in management of congenital extrahepatic
      portosystemic shunt.
AB  - BACKGROUND AND AIMS: Congenital extrahepatic portosystemic shunt (CEPS) is a rare
      venous malformation in which mesenteric venous blood drains directly into the
      systemic circulation. It is still a matter of debate whether conservative or
      operative strategies should be used to treat symptomatic CEPS. The aim of this
      study was to evaluate the role of operative intervention in the management of
      CEPS. METHODS: Between June 2004 and August 2010, 6 consecutive patients with
      symptomatic CEPS were treated in our department. There were 3 male and 3 female
      patients, with a median age of 3.5 years (range, 1-8). Their demographic,
      clinical, and laboratory data were analyzed. All patients were scheduled to
      undergo shunt ligation or liver transplantation (LT). RESULTS: Living donor LT
      was carried out in 4 patients, and shunt ligation in 2. After a median follow-up
      of 25 months, all the patients are alive currently with marked relief of
      symptoms. CONCLUSION: Shunt ligation or LT for symptomatic CEPS is potentially
      curative.

PMID- 21962401
TI  - Dietary omega-3 polyunsaturated fatty acid intake is related to a protective high
      density lipoprotein subspecies profile independent of genetic effects: a
      monozygotic twin pair study.
AB  - BACKGROUND: Studies on diet and high-density lipoprotein (HDL) subspecies
      distribution are limited. OBJECTIVE: We examined the relationship between
      macronutrient composition and lipoprotein particle size and HDL subspecies
      independent of genetic effects by studying monozygotic (MZ) twins. METHODS: 24
      healthy MZ twin pairs aged 23-33 years were identified from two longitudinal
      population-based studies, FinnTwin16 and FinnTwin12. Total energy and nutrient
      intake were assessed with 3-day food records and physical activity was measured
      by the Baecke index. HDL subspecies distribution was determined by non-denaturing
      gradient gel electrophoresis. Associations between diet composition and HDL mean
      particle size were determined by multivariate nutrient density models adjusted
      for confounding variables. RESULTS: Substituting one energy percentage from omega
      3 polyunsaturated fatty acids (n-3 PUFAs) for a corresponding amount of energy
      from other type of fats was related to changes in the relative proportions of the
      HDL subspecies 2b, 3a and 3b toward a larger mean particle size in men (beta +/-
      SE: 1.00 +/- 0.26 nm, p = 0.004) and women (beta +/- SE: 0.90 +/- 0.21 nm, p =
      0.001). This association remained significant in analyses controlling for genetic
      and shared environmental influences using within-pair differences of the measures
      in MZ twin pairs (beta +/- SE: 0.37 +/- 0.14 nm, p = 0.019). Twins with the
      higher n-3 PUFA intake had significantly higher proportions of large HDL(2b)
      particles and lower proportions of smaller-sized HDL(3a) and HDL(3b) particles as
      compared to their co-twins with lower intakes (p < 0.05). CONCLUSIONS: Our data
      suggest that n-3 PUFA intake is associated with a favorable change in the
      distribution of HDL subspecies towards larger particles independent of genetic
      and shared environmental factors.

PMID- 21962402
TI  - Circulating leukocyte telomere length and oxidative stress: a new target for
      statin therapy.
AB  - OBJECTIVES: We investigated the relationship between prior statin therapy and
      leukocyte telomere length (LTL), as well as their interaction with potential new
      biomarkers of oxidative deoxyribonucleic acid (DNA) lesions and reactive oxygen
      species-induced inflammation. METHODS AND RESULTS: From patients admitted for an
      acute myocardial infarction, LTL was assessed by quantitative polymerase chain
      reaction (Q-PCR), and leukocyte Finkel-Biskis-Jinkins osteosarcoma (FOS) and 8
      oxoguanine DNA glycosylase (OGG1) messenger ribonucleic acid (mRNA) levels were
      measured by retrotranscription Q-PCR. Patients under prior chronic statin therapy
      were compared with patients without statin therapy. Although patients on statin
      therapy were older, their mean LTL was longer than patients not under statin
      therapy (1.29 +/- 0.11 vs. 1.25 +/- 0.11 T/S ratio, p = 0.008). In contrast, FOS
      and OGG1 mRNA levels were similar for the 2 groups. LTL decreased with increasing
      age, FOS, and OGG1 mRNA levels. Statin therapy remained associated with longer
      LTL, even after adjustment for confounding factors (p = 0.001), and in younger
      patients (<= 64 y). Even in groups matched for propensity scores for statin use,
      LTL was markedly longer in patients under statin therapy. CONCLUSIONS: Our
      observational study showed that statin therapy was associated with longer LTL.
      These data bring to light opportunities to identify new targets for early primary
      preventive treatment strategies. Moreover, our study raised FOS and OGG1 as new
      relevant biomarkers of LTL.

PMID- 21962403
TI  - Impact of soluble TWEAK and CD163/TWEAK ratio on long-term cardiovascular
      mortality in patients with peripheral arterial disease.
AB  - AIM: Soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) has
      recently been introduced as a potential mediator of cardiovascular disease. We
      examined the associations between sTWEAK, its scavenger receptor sCD163,
      sCD163/sTWEAK ratio and risk for long-term all-cause and cardiovascular mortality
      in patients with lower-extremity peripheral arterial disease (PAD). METHODS:
      sTWEAK and sCD163 serum levels were measured retrospectively in a cohort of 295
      patients with symptomatic PAD followed for 6.1+/-2.1 years. The endpoints were
      defined as all-cause or cardiovascular death. The relationship between sTWEAK,
      sCD163 levels, sCD163/sTWEAK ratio, and times to fatal outcome was examined by
      Cox proportional hazards analysis. RESULTS: sTWEAK levels were significantly
      lower (672 (IQR 515; 872)pg/ml vs. 814 (IQR 673; 957)pg/ml, p < 0.0001), and
      sCD163/sTWEAK ratio significantly higher (0.91 (IQR 0.63; 1.37) vs. 0.77 (IQR
      0.55; 1.12), p = 0.008) in patients with critical limb ischemia (CLI) on
      admission as compared with those with intermittent claudication (IC). During
      follow-up, 80 (27%) patients died, hereof 33 (11.5%) of cardiovascular causes.
      Cox regression analysis revealed that an increase of 100 pg/ml of baseline sTWEAK
      were associated with a decreased risk for all cause [adjusted hazard ratio (HR)
      0.89 (95%CI (0.80-0.99)), p = 0.043] and cardiovascular mortality [adjusted HR
      0.83 (95% CI (0.69-0.99)), p = 0.038]. The patients with lower sTWEAK
      concentrations had a higher risk for cardiovascular death being more than two
      times as great as patients in the two upper tertiles (adjusted HR 2.2, 95% CI
      (1.06-4.87), p = 0.035). Similarly, the risk of cardiovascular death was 3-fold
      increased for patients in the upper tertile of sCD163/sTWEAK ratio as comparing
      with the patients in two lower tertiles (adjusted HR 3.04, 95% CI (1.44-6.43), p
      = 0.004). The model including sCD163/sTWEAK ratio have shown a significant
      improvement in accuracy of cardiovascular death prediction (the area under ROC
      curve 0.79 (0.72-0.86) vs. 0.84 (0.78-0.90), p = 0.019). CONCLUSIONS: Decreased
      sTWEAK concentration, and increased sCD163/sTWEAK ratio were significantly and
      independently associated with long-term cardiovascular mortality in patients with
      lower-extremity PAD.

PMID- 21962404
TI  - Strategies used during a challenging weighted walking task in healthy adults and
      individuals with knee osteoarthritis.
AB  - Knee osteoarthritis (OA) is a disease that affects millions of people. While
      numerous gait differences have been identified between healthy adults and adults
      with knee OA under normal and challenging conditions, adults with knee OA have
      not been studied during a challenging weighted walking task. Investigation of the
      effect of weighted walking on the initial contact and loading response phases of
      gait was undertaken in 20 healthy and 20 knee OA subjects ages 40-85 years old
      walking at 1.0m/s while unweighted and weighted with 1/6th of their body weight
      in a weight vest. Subjects were grouped according to their Kellgren and Lawrence
      radiographic score and healthy subjects were age-matched to those with knee OA.
      ANOVA revealed significant effects for hip flexion angle at initial contact, step
      length, initial double support percent, and load rate. Post hoc t-tests revealed
      that subjects with knee OA had a larger initial double support percent and hip
      flexion angle at initial contact and a decreased load rate compared to
      unweighted, healthy adults. Also, both groups increased their initial double
      support percent in response to the challenging weighted walking task, but only
      the healthy adults increased their hip flexion angle at initial contact and
      decreased their load rate. During the weighted condition, the knee OA group had a
      shorter step length compared to the healthy group. Because the knee OA group only
      made minor compensations to their gait strategy, it appears that they may be
      unable or prefer not to adjust their gait mechanics due to underlying issues.

PMID- 21962405
TI  - Arm swing asymmetry in Parkinson's disease measured with ultrasound based motion
      analysis during treadmill gait.
AB  - The reduction of arm swing during gait is a frequent phenomenon in patients with
      early Parkinson's disease (PD). However, the objective quantification of this
      clinical sign using treadmill-based gait analysis has not been systematically
      evaluated so far. We simultaneously measured ultrasound based limb kinematics and
      spatiotemporal gait parameters during treadmill walking at different speeds in 21
      early PD patients in Hoehn and Yahr (HY) stage I, 19 patients with bilateral PD
      in HY stage II and 25 age-matched controls. Both PD groups showed a highly
      significant reduction of the arm swing amplitude on the more affected body side
      (MAS). Decomposing total arm swing resulted in a bilateral decrease of arm
      retroversion in both PD groups, whereas anteversion was normal on the less
      affected side of the HY I cohort. Early stage patients exhibited a highly
      significant, almost threefold increase of the arm swing asymmetry index (I(A))
      compared with controls. Reduced retroversion on the MAS and increased arm swing
      I(A) were the independent variables with the closest association to disease
      status in a multivariate logistic regression analysis. We conclude that
      ultrasound based motion analysis during treadmill walking allows reliable
      investigation of asymmetric arm movements in early PD patients which attenuate
      with ongoing disease. Impaired active arm retroversion seems to be the earliest
      sign of upper extremity dysfunction in parkinsonian gait. The measurement of limb
      kinematics during treadmill gait can broaden our methodological line-up for the
      analysis of complex motor programs in movement disorders.

PMID- 21962406
TI  - Relationships between motor function and gait-related dual-task interference
      after stroke: a pilot study.
AB  - The purpose of this pilot study was to examine the relationships between motor
      performance measures and dual-task interference in gait among community-dwelling
      adults with stroke. Dual-task costs on gait were correlated with Fugl-Meyer lower
      extremity score and usual gait speed in 13 community-dwelling adults with stroke.
      Individuals with greater lower extremity motor impairment and slower gait speed
      experienced greater cognitive-motor interference in gait. Paretic single limb
      stance was particularly susceptible to dual-task interference. Gait speed was
      only vulnerable to dual-task interference in the most complex dual-task. Thus,
      global characteristics of gait were vulnerable in the most difficult cognitive
      tasks, but even easy tasks impaired discrete components of dynamic balance.

PMID- 21962407
TI  - The role of vision in Parkinson's disease locomotion control: free walking task.
AB  - The current study addressed the role of visual information in the control of
      locomotion in people with Parkinson's disease. Twelve healthy individuals and 12
      mild to moderate Parkinson's disease patients were examined while walking at self
      selected velocities, under three visual sampling conditions: dynamic (normal
      lighting), static (static visual samples) and voluntary visual sampling. Subjects
      wore liquid crystal glasses for visual manipulation. Outcome measures included
      spatial-temporal parameters, braking and propulsive impulses, number of samples
      and total duration of voluntary visual samples. Interaction between groups and
      visual conditions was not observed for kinematic parameters or braking and
      propulsive impulses. There were no significant differences between groups for
      voluntary visual sampling variables. These findings suggest that the visual
      control of locomotion in Parkinson's disease patients was similar to that
      observed in controls. Furthermore, Parkinson's disease patients were not more
      dependent on visual information than healthy individuals for the locomotion
      control.

PMID- 21962408
TI  - Canine parvovirus--a review of epidemiological and diagnostic aspects, with
      emphasis on type 2c.
AB  - Canine parvovirus type 2 (CPV-2) emerged in late 1970s causing severe epizootics
      in kennels and dog shelters worldwide. Soon after its emergence, CPV-2 underwent
      genetic evolution giving rise consecutively to two antigenic variants, CPV-2a and
      CPV-2b that replaced progressively the original type. In 2000, a new antigenic
      variant, CPV-2c, was detected in Italy and rapidly spread to several countries.
      In comparison to the original type CPV-2, the antigenic variants display
      increased pathogenicity in dogs and extended host range, being able to infect and
      cause disease in cats. Epidemiological survey indicate that the newest type CPV
      2c is becoming prevalent in different geographic regions and is often associated
      to severe disease in adult dogs and also in dogs that have completed the
      vaccination protocols. However, the primary cause of failure of CPV vaccination
      is interference by maternally derived immunity. Diagnosis of CPV infection by
      traditional methods has been shown to be poorly sensitive, especially in the late
      stages of infections. New diagnostic approaches based on molecular methods have
      been developed for sensitive detection of CPV in clinical samples and rapid
      characterisation of the viral type. Continuous surveillance will help assess
      whether there is a real need to update currently available vaccines and
      diagnostic tests.

PMID- 21962409
TI  - Characterization of the probiotic strain Vagococcus fluvialis in the protection
      of European sea bass (Dicentrarchus labrax) against vibriosis by Vibrio
      anguillarum.
AB  - Aquaculture is one of the main sources of income in many countries worldwide.
      Intensive farms are often affected by different infectious diseases that can
      decrease their final production. To control this situation, several antibiotics
      are frequently used with known environmental consequences. The aim of this study
      was to analyze different bacterial strains isolated from of gilthead sea bream,
      sea bass, sole and meagre guts, for use as probiotics in aquaculture. The strains
      were evaluated in vitro through various mechanisms of selection, such as the
      production of antagonistic effects against pathogens, production of antibacterial
      substance, adhesion to the intestinal mucus, competition for nutrients or binding
      site, and growth in intestinal mucus. A total of 50 bacterial strains were
      analyzed and only one showed excellent in vitro results for consideration as a
      candidate to be analyzed in vivo. The strain, identified as Vagococcus fluvialis,
      showed good protection against Vibrio anguillarum 975-1 in vivo in the
      experimental challenge, showing a relative percent survival of 42.3% higher than
      positive control group. Therefore, in conclusion we consider this strain to be a
      good candidate for use as a future probiotic in aquaculture.

PMID- 21962410
TI  - Descriptive epidemiology of Moraxella bovis, Moraxella bovoculi and Moraxella
      ovis in beef calves with naturally occurring infectious bovine
      keratoconjunctivitis (Pinkeye).
AB  - PROBLEM ADDRESSED: Infectious bovine keratoconjunctivitis (IBK) is an ocular
      disease that causes substantial weight loss in beef calves. OBJECTIVE: The
      objective of this study was to evaluate the association between Moraxella
      bovoculi, Moraxella bovis and Moraxella ovis and IBK incidence. METHODS AND
      APPROACH: A cohort design was used. From 239 calves and 478 eyes, 77 randomly
      chosen eyes were monitored for M. bovoculi, M. bovis, M. ovis and IBK incidence
      over 4 months. One hypothesis tested was that IBK hazard in eyes was not
      associated with detection of M. bovoculi, M. bovis and M. ovis. A secondary
      hypothesis tested that IBK cases were not associated with increased prevalence of
      M. bovoculi, M. bovis and M. ovis. RESULTS: 23% of 77 eyes developed IBK. M. ovis
      was identified in one IBK-negative eye. The adjusted hazard ratio (HR) for IBK
      incidence from eyes where M. bovoculi or M. bovis were recovered prior to disease
      occurrence were not statistically significant (M. bovoculi HR=1.38, 95% CI: 0.54
      3.53, p=0.49, M. bovis HR=1.60, 95% CI: 0.48-5.53, p=0.44). The adjusted hazard
      ratio for M. bovoculi in IBK lesions was 6.45 (95% CI: 3.35-12.44, p<0.001). The
      adjusted hazard ratio for M. bovis in IBK lesions was 2.33 (95% CI: 1.22-4.45,
      p=0.01). CONCLUSION: A temporal association between prior exposure to M. bovoculi
      or M. bovis and subsequent IBK incidence was not demonstrated. However, M.
      bovoculi and M. bovis are more frequently recovered from eyes with IBK lesions
      than unaffected eyes and this provides weak evidence for a causal role.

PMID- 21962412
TI  - Translocation of arsenic contents in vegetables from growing media of
      contaminated areas.
AB  - The aim of this study was to evaluate the translocation of arsenic (As) by
      different vegetables grown in agricultural soil irrigated for long period with
      tube well water as test vegetable samples and compared those vegetables of same
      species grown in agricultural soil irrigated with fresh canal water marked as
      control vegetable samples. Moreover, the total and ethylene-diamine-tetra acetic
      acid (EDTA) extractable contents of As in soil irrigated by tube well and canal
      water were determined and correlate with total concentrations of As in edible
      parts of vegetables. Statistically significant correlations were obtained between
      the total and EDTA extractable fractions of As in soil. High level of total and
      EDTA extractable As were found in tested vegetable samples as compared to
      controlled vegetable samples. This investigation highlights the increased danger
      of growing vegetables in the agricultural land continuously irrigated by As
      contaminated water.

PMID- 21962411
TI  - In vitro antifungal susceptibility of Malassezia pachydermatis from dogs with and
      without skin lesions.
AB  - Canine Malassezia dermatitis is frequently treated with systemic ketoconazole
      (KTZ) and itraconazole (ITZ). However, no information is available on the
      antifungal susceptibility to azoles and allilamine of Malassezia pachydermatis
      isolates from dogs with or without skin lesions. The present study was designed
      to evaluate the in vitro antifungal susceptibility of M. pachydermatis strains
      from dogs with or without skin lesions to KTZ, ITZ, miconazole (MICO),
      fluconazole (FLZ), posaconazole (POS), voriconazole (VOR) and terbinafine (TER)
      using the Clinical and Laboratory Standards Institute reference Broth
      Microdilution Method (CLSI M27-A2). The association between the susceptibility to
      antifungal compounds and the origin of M. pachydermatis, from skin with or
      without lesions has been also assessed. A total of 62 M. pachydermatis strains
      from healthy dogs (i.e., Group A=30) or with skin lesions (i.e., Group B=32) were
      tested. ITZ, KTZ and POS showed the highest activity against M. pachydermatis
      strains, whereas MICO TER and FLZ the lowest. A higher number of Malassezia
      resistant strains were registered among isolates from Group B than those from
      Group A. This study indicates that M. pachydermatis strains were susceptible to
      ITZ, KTZ, and POS. However, dogs with lesions may harbour strains with low
      susceptibility to antifungal agents and displaying cross-resistance phenomena to
      azole. The antifungal therapy in Malassezia infections requires careful appraisal
      of choice of drugs especially in cases of unresponsiveness to antifungal
      treatment or recurrent infections.

PMID- 21962413
TI  - Effects of 1,2,4-trichlorobenzene on the enzyme activities and ultrastructure of
      earthworm Eisenia fetida.
AB  - Adult Eisenia fetida earthworms were exposed to sub-lethal concentrations of
      1,2,4-trichlorobenzene to assess the toxicity of contaminated soils. The LC50 of
      1,2,4-TCB at 7 and 14 d were 945+/-175 and 890+/-169 mg kg-1. A lower dose of
      1,2,4-TCB (25 mg g-1) had stimulatory effects on SOD and AChE activities, but
      AChE activities were significantly inhibited at higher treatment levels (100 and
      400 mg g-1). SOD activities increased after 2, 7, and 14 d of exposure, but AChE
      activities were significantly inhibited at 400 mg/kg 1,2,4-TCB after 2, 7, and 14
      d of exposure, and the inhibition rates were 25.41%, 28.65%, and 25.05%.
      Ultrastructural observation of the intestinal epithelium at three concentrations
      (control, 50, and 400 mg g-1) revealed that the epicuticle, cuticle layer, and
      microvilli were damaged with increasing 1,2,4-TCB concentration. At 400 mg kg-1,
      mitochondria were seriously injured and the smooth endoplasmic reticulum was
      seriously dilated.

PMID- 21962414
TI  - Russula cutefracta inhibits antigen-induced degranulation and Syk and MAPK
      phosphorylation in rat basophilic leukaemia cells.

PMID- 21962415
TI  - The effect of progressive, reinforcing telephone education and counseling versus
      brief educational intervention on knowledge, self-care behaviors and heart
      failure symptoms.
AB  - BACKGROUND: The optimal strategy for promoting self-care for heart failure (HF)
      is unclear. METHODS AND RESULTS: We conducted a randomized trial to determine
      whether a "teach to goal" (TTG) educational and behavioral support program
      provided incremental benefits to a brief (1 hour) educational intervention (BEI)
      for knowledge, self-care behaviors, and HF-related quality of life (HFQOL). The
      TTG program taught use of adjusted-dose diuretics and then reinforced learning
      goals and behaviors with 5 to 8 telephone counseling sessions over 1 month.
      Participants' (n = 605) mean age was 61 years; 37% had marginal or inadequate
      literacy; 69% had ejection fraction <0.45; and 31% had Class III or IV symptoms.
      The TTG group had greater improvements in general and salt knowledge (P < .001)
      and greater increases in self-care behaviors (from mean 4.8 to 7.6 for TTG vs.
      5.2 to 6.7 for BEI; P < .001). HFQOL improved from 58.5 to 64.6 for the TTG group
      but did not change for the BEI group (64.7 to 63.9; P < .001 for the difference
      in change scores). Improvements were similar regardless of participants' literacy
      level. CONCLUSIONS: Telephone reinforcement of learning goals and self-care
      behaviors improved knowledge, health behaviors, and HF-related QOL compared to a
      single education session.

PMID- 21962416
TI  - Activity with ambulation attenuates diuretic responsiveness in chronic heart
      failure.
AB  - INTRODUCTION: We hypothesized that discharged heart failure (HF) patients could
      develop clinical congestion despite adhering to prescribed diuretics, because
      ambulation attenuates diuretic and natriuretic responsiveness. METHODS: We
      studied 9 patients aged 57 +/- 13 (mean +/- SD) years with New York Heart
      Association functional class II-III symptoms and ejection fraction <40% (28 +/-
      7%) and receiving furosemide (>=80 mg/d [113 +/- 53 mg/d]) plus renin-angiotensin
      system antagonists and beta-blockade. Inulin and p-amminohippuric acid were
      infused to estimate glomerular filtration rate (GFR) and renal plasma flow (RPF).
      Furosemide was administered intravenously at 75% of the usual oral morning dose.
      Participants were randomized to supine (90 minutes recumbancy) or upright (90
      minutes sitting and treadmill walking) posture and assumed the other position on
      their second day. Primary outcome variables were urine volume and sodium
      excretion 90 minutes after furosemide. RESULTS: On the upright, compared with the
      supine, day, urine volume (792 +/- 484 vs 1,290 +/- 503 mL; P = .02) and sodium
      (79 +/- 55 vs 141 +/- 61 mmol; P < .01) were attenuated, whereas plasma
      norepinephrine (4.4 +/- 2.7 vs 2.3 +/- 1.8 mmol/L; P = .01) and renin (327 +/-
      250% of supine; P < .01) were augmented. Urinary K+, mean pressure, GFR, and RPF
      were similar. CONCLUSIONS: Activation of the sympathetic nervous system and renin
      angiotensin axis by upright ambulation may attenuate diuresis and natriuresis by
      increasing proximal tubular reabsorption of sodium and water.

PMID- 21962417
TI  - Found in translation.

PMID- 21962418
TI  - Functional mitral regurgitation: a link to pulmonary hypertension in heart
      failure with preserved ejection fraction.
AB  - BACKGROUND: Patients with heart failure with preserved ejection fraction (HFpEF)
      may present with Pulmonary hypertension (PH) and functional mitral regurgitation
      (MR). Whether PH is linked to the presence of functional MR has not been
      investigated in HFpEF patients. METHODS AND RESULTS: Systolic pulmonary artery
      pressure (sPAP) and functional MR were assessed by 2-dimensional Doppler
      echocardiography in 70 ambulatory HFpEF patients and 70 hypertensive control
      subjects free of organic mitral valve lesions, significant valve disease, and
      comorbid conditions associated with PH. Whereas none of control subjects had more
      than trivial MR, 21 patients with HFpEF had functional MR (mean mitral effective
      regurgitant orifice, regurgitant volume, and regurgitant fraction 7 +/- 3 mm,(2)
      15 +/- 8 mL, and 28 +/- 14%, respectively). Pulmonary hypertension (sPAP >35 mm
      Hg) was significantly more prevalent in HFpEF patients with functional MR than in
      HFpEF patients without functional MR (62 vs 22%; P = .002). Functional MR
      remained an independent predictor of PH in HFpEF patients (P = .004) after
      adjustment on mitral E wave to e' mitral annulus velocity ratio (E/e'; P = .022)
      and left atrial volume index (P = .025). Systolic PAP and E/e' were greater in
      HFpEF patients than in control subjects (35 +/- 9 vs 29 +/- 8 mm Hg [P < .0001]
      and 13 +/- 6 vs 11 +/- 5 [P = .018], respectively). Systolic PAP remained greater
      in HFpEF patients than in control subjects after adjusting for E/e' (P = .002).
      CONCLUSIONS: Pulmonary hypertension appears to be linked to the presence of
      functional MR in HFpEF patients.

PMID- 21962419
TI  - Inhaled iloprost for patients with precapillary pulmonary hypertension and right
      side heart failure.
AB  - BACKGROUND: Pulmonary hypertension (PH) can lead to right-side heart failure
      (RHF) and death. There are no therapeutic recommendations for patients
      experiencing acute RHF in the course of PH. This study aimed to examine the
      safety and efficacy of inhaled iloprost in patients with precapillary PH and RHF.
      METHODS AND RESULTS: Between October 2007 and December 2008, 7 patients with
      precapillary PH and RHF were enrolled. Per protocol, iloprost was inhaled hourly
      for a minimum of 12 hours during a 24-hour period. The starting dose of 2.5 MUg
      was increased hourly by 2.5 MUg as long as the increases were tolerated. Safety
      and efficacy were determined by continuous invasive monitoring of systemic and
      pulmonary hemodynamic parameters. Systemic pressures remained stable during
      inhalation (66.1 +/- 6.9 mm Hg at baseline and 69.1 +/- 6.4 mm Hg immediately
      after inhalation therapy, P = 0.48). Cardiac index increased from 2.4 +/- 0.7
      L/min/m(2) to 2.9 +/- 0.9 L/min/m(2) (P = .008). Pulmonary vascular resistance
      decreased from 634.6 +/- 218.3 dyn.s.cm(-5) to 489.6 +/- 173.8 dyn.s.cm(-5) (P =
      .044), and N-terminal B-type natriuretic peptide levels decreased from 13,591 +/-
      10,939 pg/mL to 9,944 +/- 8,569 pg/mL (P = .051). CONCLUSION: Blood pressure
      guided hourly inhalation of iloprost may offer a safe and effective strategy for
      the treatment of PH patients with RHF.

PMID- 21962420
TI  - Serum pregnancy-associated plasma protein a in patients with heart failure.
AB  - BACKGROUND: Pregnancy-associated plasma protein A (PAPP-A) proteolyzes insulin
      like growth factor (IGF)-binding proteins and thus increases IGF-1 bioactivity.
      PAPP-A has been reported to be involved in various pathophysiologic
      abnormalities; however, the clinical significance of PAPP-A has not been examined
      in cases of heart failure (HF). We hypothesized that PAPP-A levels might be
      correlated with the severity of HF. METHODS AND RESULTS: PAPP-A and B-type
      natriuretic peptide (BNP) levels were measured in 262 subjects (182 HF patients
      and 80 control subjects). PAPP-A levels were higher in patients with HF than in
      control subjects and increased with advancing New York Heart Association
      functional class. There were 53 cardiac events during a mean follow-up period of
      796 days. PAPP-A levels were higher in patients with cardiac events than in event
      free patients. Patients were divided into 3 groups on the basis of their PAPP-A
      and BNP levels. Kaplan-Meier analysis demonstrated that the group with both high
      BNP with high PAPP-A had a significantly higher cardiac event rate than other
      groups. CONCLUSIONS: Serum PAPP-A levels were related to the severity of HF and
      associated with a high risk for adverse cardiac events in HF patients, suggesting
      that PAPP-A might be involved in the pathogenesis of HF.

PMID- 21962421
TI  - Right ventricular energetics in patients with hypertrophic cardiomyopathy and the
      effect of alcohol septal ablation.
AB  - BACKGROUND: Diastolic dysfunction in hypertrophic cardiomyopathy (HCM) is
      accompanied by augmented left ventricular (LV) end-diastolic pressure, above all
      in the presence of LV outflow tract (LVOT) obstruction. Increased back-pressure
      may augment right ventricular (RV) afterload and induce an oxidative metabolic
      imbalance between the 2 ventricles. The aim was to study right-to-left
      ventricular oxidative metabolism in HCM and the effects of alcohol septal
      ablation (ASA). METHODS AND RESULTS: Twenty-one HCM patients were enrolled.
      Eleven healthy subjects served as a control group. Subjects underwent 2
      dimensional echocardiography to assess LVOT gradient, left atrial size, and
      diastolic function. [(11)C]Acetate positron-emission tomography (PET) was
      performed to determine RVk(2) and LVk(2), as a noninvasive index of oxidative
      metabolism. Seven HCM patients with LVOT obstruction, scheduled to undergo ASA,
      were also studied 6 months after the procedure. RVk(2) was higher in HCM patients
      than i control subjects (0.081 +/- 0.021 min(-1) vs. 0.061 +/- 0.017 min(-1); P =
      .05), whereas LVk(2) was similar between groups. Consequently, RVk(2)/LVk(2) was
      increased in the patients (0.85 +/- 0.19 vs 0.59 +/- 0.13; P = .004). In patients
      with obstructive HCM, ASA reduced RVk(2) (0.085 +/- 0.021 min(-1) to 0.072 +/-
      0.022 min(-1); P = .001). Inasmuch as LVk(2) remained unaffected by the
      procedure, RVk(2)/LVk(2) was decreased after ASA (0.66 +/- 0.18; P = .03). The
      absolute change in LVOT gradient was related to the absolute change in RVk(2) (r
      = 0.77; P = .044). CONCLUSIONS: In HCM patients, RV oxygen consumption is
      increased in relation to the LV. ASA reduces RV oxygen consumption in HCM
      patients with LVOT obstruction, suggesting that increased LV loading conditions
      and diastolic dysfunction play a predominant role in augmenting RV workload in
      these patients.

PMID- 21962423
TI  - Alcoholic cardiomyopathy: a review.
AB  - Alcohol abuse can cause cardiomyopathy indistinguishable from other types of
      dilated nonischemic cardiomyopathy. Most heavy drinkers remain asymptomatic in
      the earlier stages of disease progression, and many never develop the familiar
      clinical manifestations that typify heart failure. We review the current thinking
      on the pathophysiology, clinical characteristics, and treatments available for
      alcoholic cardiomyopathy. The relationship of alcohol to heart disease is
      complicated by the fact that in moderation, alcohol has been shown to afford a
      certain degree of protection against cardiovascular disease.

PMID- 21962424
TI  - Noninvasive ventilation in acute cardiogenic pulmonary edema: a meta-analysis of
      randomized controlled trials.
AB  - BACKGROUND: The evidence of individual studies in acute cardiogenic pulmonary
      edema (ACPE) supporting noninvasive ventilation (NIV) is still inconclusive,
      particularly regarding noninvasive positive pressure ventilation (NIPPV).
      METHODS: We carried out a meta-analysis. We searched in the Embase, Medline,
      Cinahl, Dare, Coch, Central, and CNKI databases and congress abstracts for trials
      comparing continuous positive airway pressure (CPAP) or NIPPV with standard
      therapy (ST). To assess treatment effects, we carried out direct comparison using
      a random effects model and adjusted indirect comparison. RESULTS: At total of 34
      studies (3,041 patients) were included. In direct comparisons, both CPAP and
      NIPPV reduced the risk of death (relative risk [RR] 0.64, 95% CI 0.44-0.93; RR
      0.80, 95% CI 0.58-1.10; respectively) compared with ST, although only CPAP had a
      significant effect. There were no significant differences between NIPPV and CPAP.
      Pooled results of direct and adjusted indirect comparisons showed that compared
      with ST, both CPAP and NIPPV significantly reduced mortality (RR 0.63, 95% CI
      0.44-0.89; RR 0.73, 95% CI 0.55-0.97; respectively). CONCLUSIONS: Our findings
      suggest that among ACPE patients, NIV delivered through either NIPPV or CPAP
      reduced mortality.

PMID- 21962422
TI  - Nurse-Enhanced Memory Intervention in Heart Failure: the MEMOIR study.
AB  - BACKGROUND: Many patients with heart failure (HF) have cognitive deficits,
      including memory loss. OBJECTIVES: The aim of this study was to evaluate the
      efficacy of a cognitive training intervention on memory (primary outcome),
      working memory, psychomotor speed, executive function, and performance of
      cognitive activities and instrumental activities of daily living (IADLs). METHODS
      AND RESULTS: Forty patients with HF were randomly assigned to the computerized
      plasticity-based cognitive training intervention called Brain Fitness or to the
      health education active control intervention. Advanced practice nurses made
      weekly home visits to assess symptoms and monitor intervention adherence.
      Patients completed demographic and clinical data (baseline), neuropsychologic
      tests (baseline and 8 and 12 weeks), and measures of cognitive and IADLs
      performance (baseline and 12 weeks) and satisfaction (12 weeks). Linear mixed
      models analyses indicated a significant group by time interaction for delayed
      recall memory (P = .032) and a significant time effect for total (list learning)
      (P < .001) and delayed (P = .015) recall memory, psychomotor speed (P = .029),
      and performance of IADLs (P = .006). Intervention adherence and patient
      satisfaction were high. CONCLUSIONS: To our knowledge, this was the first test of
      Brain Fitness in HF. Although it was a preliminary study with limitations,
      results support the need for a larger randomized controlled trial to determine
      whether the memory loss of HF is amenable to plasticity-based interventions.

PMID- 21962425
TI  - Mortality reduction of cardiac resynchronization and implantable cardioverter
      defibrillator therapy in heart failure: an updated meta-analysis. Does recent
      evidence change the standard of care?
AB  - BACKGROUND: The recent publication of the MADIT-CRT and RAFT trials has more than
      doubled the number of patients in which a direct comparison of the combination of
      cardiac resynchronization therapy (CRT) and implantable cardioverter
      defibrillator (ICD) versus ICD alone was carried out. The present meta-analysis
      aims to assess the impact of combined CRT and ICD therapy on survival of heart
      failure (HF) patients. METHODS AND RESULTS: Medline, Embase, and the Cochrane
      Library databases were searched, and all randomized controlled trials of CRT
      alone or combined with ICDs in HF resulting from left ventricular systolic
      dysfunction were included. Main outcome was all-cause mortality. Summary relative
      risk (RR) and 95% confidence interval (CI) were calculated employing random
      effects models. Twelve studies were included, with a total of 8,284 randomized
      patients. For the comparison of CRT alone versus medical therapy, pooled analysis
      of 5 available trials demonstrated a significant reduction in all-cause mortality
      with CRT (RR 0.76, 95% CI: 0.64-0.9). Pooled analysis of 6 trials that compared
      the combination of CRT and ICD therapy to ICD alone also showed a statistically
      significant reduction in all-cause mortality (RR 0.83, 95% CI: 0.72-0.96).
      Stratified analysis showed significant mortality reductions in all New York Heart
      Association class subgroups, with greater effect in classes III-IV (RR 0.70; 95%
      CI: 0.57-0.88). Pooled estimates of implant-related risks were 0.6% for death and
      8% for implant failure. CONCLUSION: Combined CRT and ICD therapy reduces overall
      mortality in HF patients when compared with ICD alone.

PMID- 21962426
TI  - Molecular signatures of end-stage heart failure.
AB  - BACKGROUND: To date, gene expression studies related to chronic heart failure
      (CHF) have mainly involved microarray analysis of myocardial tissues. The
      potential utility of blood to infer the etiology, pathogenesis, and course of CHF
      remains unclear. Further, the use of proteomic and metabolomic platforms for
      molecular profiling of CHF is relatively unexplored. METHODS: Microarray genomic,
      iTRAQ proteomic, and nuclear magnetic resonance metabolomic analyses were carried
      out on blood samples from 29 end-stage CHF patients (16 ischemic heart disease
      [IHD], 13 nonischemic cardiomyopathy [NICM]), and 20 normal cardiac function
      (NCF) controls. Robust statistical tests and bioinformatical tools were applied
      to identify and compare the molecular signatures among these subject groups.
      RESULTS: No genes or proteins, and only two metabolites, were differentially
      expressed between IHD and NICM patients at end stage. However, CHF versus NCF
      comparison revealed differential expression of 7,426 probe sets, 71 proteins, and
      8 metabolites. Functional enrichment analyses of the CHF versus NCF results
      revealed several in-common biological themes and potential mechanisms underlying
      advanced heart failure. CONCLUSION: Multiple "-omic" analyses support the
      convergence of dramatic changes in molecular processes underlying IHD and NICM at
      end stage.

PMID- 21962427
TI  - Carvedilol for the treatment of benign prostatic hypertrophy in patients with
      heart failure?
AB  - Heart failure (HF) and benign prostatic hypertrophy (BPH) are two conditions that
      commonly coexist in men 60 years and older. Carvedilol is the only beta
      adrenergic blocker approved for HF that also has additional alpha1-adrenergic
      blockade. As alpha1-adrenergic blockers are used in the treatment of BPH, it is
      intuitive that carvediolol could improve BPH symptoms. We present a case where
      carvedilol was replaced with bisoprolol resulting in acute urinary retention.
      When carvediolol was reinstituted, the patient's symptoms of BPH resolved. Benign
      prostatic hypertrophy was later diagnosed by digital rectal exam. Six month after
      reinstituting the carvediolol, the patient remains free of his BPH symptoms. This
      case suggests that carvedilol may be considered for the management of HF with
      systolic dysfunction in patients with concomitant BPH thus eliminating the need
      for an alpha1-adrenergic blockers.

PMID- 21962428
TI  - Reactivity of activated versus nonactivated 2-(bromomethyl)aziridines with
      respect to sodium methoxide: a combined computational and experimental study.
AB  - The difference in reactivity between the activated 2-bromomethyl-1-tosylaziridine
      and the nonactivated 1-benzyl-2-(bromomethyl)aziridine with respect to sodium
      methoxide was analyzed by means of DFT calculations within the supermolecule
      approach, taking into account explicit solvent molecules. In addition, the
      reactivity of epibromohydrin with regard to sodium methoxide was assessed as
      well. The barriers for direct displacement of bromide by methoxide in methanol
      are comparable for all three heterocyclic species under study. However, ring
      opening was found to be only feasible for the epoxide and the activated
      aziridine, and not for the nonactivated aziridine. According to these
      computational analyses, the synthesis of chiral 2-substituted 1-tosylaziridines
      can take place with inversion (through ring opening/ring closure) or retention
      (through direct bromide displacement) of configuration upon treatment of the
      corresponding 2-(bromomethyl)aziridines with 1 equiv of a nucleophile, whereas
      chiral 2-substituted 1-benzylaziridines are selectively obtained with retention
      of configuration (via direct bromide displacement). Furthermore, the
      computational results showed that explicit accounting for solvent molecules is
      required to describe the free energy profile correctly. To verify the
      computational findings experimentally, chiral 1-benzyl-2-(bromomethyl)aziridines
      and 2-bromomethyl-1-tosylaziridines were treated with sodium methoxide in
      methanol. The presented work concerning the reactivity of 2-bromomethyl-1
      tosylaziridine stands in contrast to the behavior of the corresponding 1-tosyl-2
      (tosyloxymethyl)aziridine with respect to nucleophiles, which undergoes a clean
      ring-opening/ring-closure process with inversion of configuration at the
      asymmetric aziridine carbon atom.

PMID- 21962429
TI  - Economic evaluation of drug abuse treatment and HIV prevention programs in
      pregnant women: a systematic review.
AB  - Drug abuse and transmission of HIV during pregnancy are public health problems
      that adversely affect pregnant women, their children and surrounding communities.
      Programs that address this vulnerable population have the ability to be cost
      effective due to resulting cost savings for mother, child and society. Economic
      evaluations of programs that address these issues are an important tool to better
      understand the costs of services and create sustainable healthcare systems. This
      study critically examined economic evaluations of drug abuse treatment and HIV
      prevention programs in pregnant women. A systematic review was conducted using
      the criteria recommended by the Panel on Cost-Effectiveness in Health and
      Medicine and the British Medical Journal (BMJ) checklist for economic
      evaluations. The search identified 6 economic studies assessing drug abuse
      treatment for pregnant women, and 12 economic studies assessing programs that
      focus on prevention of mother-to-child transmission (PMTCT) of HIV. Results show
      that many programs for drug abuse treatment and PMTCT among pregnant women are
      cost-effective or even cost-saving. This study identified several shortcomings in
      methodology and lack of standardization of current economic evaluations. Efforts
      to address methodological challenges will help make future studies more
      comparable and have more influence on policy makers, clinicians and the public.

PMID- 21962430
TI  - Single-step fabrication of patterned gold film array by an engineered multi
      functional peptide.
AB  - This study constitutes a demonstration of the biological route to controlled nano
      fabrication via modular multi-functional inorganic-binding peptides.
      Specifically, we use gold- and silica-binding peptide sequences, fused into a
      single molecule via a structural peptide spacer, to assemble pre-synthesized gold
      nanoparticles on silica surface, as well as to synthesize nanometallic particles
      in situ on the peptide-patterned regions. The resulting film-like gold
      nanoparticle arrays with controlled spatial organization are characterized by
      various microscopy and spectroscopy techniques. The described bio-enabled, single
      step synthetic process offers many advantages over conventional approaches for
      surface modifications, self-assembly and device fabrication due to the peptides'
      modularity, inherent biocompatibility, material specificity and catalytic
      activity in aqueous environments. Our results showcase the potential of
      artificially-derived peptides to play a key role in simplifying the assembly and
      synthesis of multi-material nano-systems in environmentally benign processes.

PMID- 21962431
TI  - A novel photoanode architecture of dye-sensitized solar cells based on TiO2
      hollow sphere/nanorod array double-layer film.
AB  - A novel TiO(2) double-layer (DL) film consisting of TiO(2) hollow spheres (HSs)
      as overlayer and single-crystalline TiO(2) nanorod arrays (RAs) as underlayer was
      designed as the photoanode of dye-sensitized solar cells (DSSCs). This new-typed
      TiO(2) HS/RA DL film could significantly improve the efficiency of DSSCs owing to
      its synergic effects, i.e. the relatively large specific surface area of TiO(2)
      HSs for effective dye adsorption, enhanced light harvesting capability originated
      from TiO(2) RA film, and rapid interfacial electron transport in one-dimensional
      TiO(2) nanorod arrays. The overall energy-conversion efficiency of 4.57% was
      achieved by the formation of TiO(2) DL film, which is 16% higher than that formed
      by TiO(2) HS film and far larger than that formed by TiO(2) RA film (eta=0.99%).
      The light absorption and interfacial electron transport, which play important
      roles in the efficiency of DSSCs, were investigated by UV-vis absorption spectra
      and electrochemical impedance spectra.

PMID- 21962432
TI  - Nanotribology-based novel characterization techniques for the dielectric charging
      failure mechanism in electrostatically actuated NEMS/MEMS devices using force
      distance curve measurements.
AB  - The work presents a comprehensive package of novel nanoscale characterization
      techniques to study dielectric charging in electrostatic nano- and
      microelectromechanical systems (NEMS and MEMS). The proposed assessment
      methodologies are based on the force-distance curve (FDC) measurements performed
      using an atomic force microscope (AFM) to measure, for the first time, the
      induced surface potential and adhesive force over charged dielectric films. They
      were employed to study plasma enhanced chemical vapor deposition (PECVD) silicon
      nitride films for application in electrostatic capacitive RF MEMS switches. Three
      different techniques were introduced including the application of FDC
      measurements to study charging in bare SiN(x) films, metal-insulator-metal (MIM)
      capacitors, and MEMS switches. The results from the three methods were correlated
      and compared with the published data from other characterization techniques,
      mainly charge/discharge current transient (C/DCT) and Kelvin probe force
      microscopy (KPFM). The unique advantages of the proposed FDC-based
      characterization techniques are twofold. First, they can measure the multiphysics
      coupling between the dielectric charging phenomenon and tribological issues at
      the interface between the switch bridge and the dielectric surface. Second, the
      FDC-based techniques can measure larger levels of induced surface potential over
      charged dielectric films which results from the high electric field normally used
      to actuate MEMS switches. Based on the proposed FDC techniques, the influence of
      several parameters on dielectric charging/discharging processes was investigated:
      the dielectric film thickness, deposition conditions, substrate, and electrical
      stress conditions.

PMID- 21962433
TI  - Experimental and theoretical investigations of evaporation of sessile water
      droplet on hydrophobic surfaces.
AB  - Experiments of sessile water droplet evaporation on both polydimethylsiloxane
      (PDMS) and Teflon surfaces were conducted. All experiments begin with constant
      contact area mode (the initial contact angle is greater than 90 degrees ), switch
      to constant contact angle mode and end with mixed mode. Based on the assumptions
      of spherical droplet and uniform concentration gradient, theoretical analyses for
      both constant contact area and constant contact angle modes are made and
      theoretical solutions are derived accordingly, especially a theoretical solution
      of contact angle is presented first for CCR stage with any value of the initial
      contact angle. Moreover, comparisons between the theoretical solutions and
      experimental data of contact angle in CCR stage demonstrate the validity of the
      theoretical solution and it would help for a better understanding and application
      of water droplet on solid surfaces, which is quite often encountered in lab-on-a
      chip, polymerase chain reaction (PCR) and other micro-fluidics devices.

PMID- 21962434
TI  - Click-chemistry for surface modification of monodisperse-macroporous particles.
AB  - In this study, click chemistry was proposed as a tool for tuning the surface
      hydrophilicity of monodisperse-macroporous particles in micron-size range. The
      monodisperse-porous particles carrying hydrophobic or hydrophilic molecular
      brushes on their surfaces were obtained by the proposed modification. Hydrophilic
      poly(glycidyl methacrylate-co-ethylene dimethacrylate), poly(GMA-co-EDM)
      particles were hydrophobized by the covalent attachment of poly(octadecyl
      acrylate-co-propargyl acrylate), poly(ODA-co-PA) copolymer onto the particle
      surface via triazole formation by click chemistry. In the second part,
      Hydrophobic poly(4-chloromethylstyrene-co-divinylbenzene), poly(CMS-co-DVB)
      particles were hydrophilized by the covalent attachment of poly(vinyl alcohol),
      PVA onto their surface also via triazole formation by click chemistry. The
      presence of PVA and poly(ODA-co-PA) copolymer on the corresponding particles was
      shown by FTIR-DRS. After click-coupling reactions applied for both hydrophobic
      poly(CMS-co-DVB) and hydrophilic poly(GMA-co-EDM) particles, the marked changes
      in surface polarity were shown by contact angle measurements. Protein adsorption
      characteristics of plain and modified particles were investigated for both
      materials. In the isoelectric point of albumin, the non-specific albumin
      adsorption decreased from 225 to 80 mg/g by grafting PVA onto the poly(CMS-co
      DVB) beads. On the other hand, the non-specific albumin adsorption onto the plain
      poly(GMA-co-EDM) beads increased from 50 to 400 mg/g by the covalent attachment
      of poly(ODA-co-PA) copolymer onto the bead-surface via click chemistry. The
      protein adsorption behavior was efficiently regulated by the covalent attachment
      of appropriate molecular brushes onto the surfaces of selected particles. The
      results indicated that "click chemistry" was an efficient tool for controlling
      the polarity of monodisperse-macroporous particles.

PMID- 21962435
TI  - Do integrated record systems lead to integrated services? An observational study
      of a multi-professional system in a diabetes service.
AB  - PURPOSE: There are few opportunities to study the use of integrated electronic
      health record (EHR) systems, where single patient records are used by a number of
      health care staff. The purpose of the study was to understand how an integrated
      electronic health record system was used by health care staff in the treatment
      and management of diabetes patients. The investigation was focused on the
      interface between the primary and secondary care services which patients access
      for their diabetes care. METHODS: Observations of the use of an integrated
      electronic health record during patients' consultations with health care staff
      were conducted over a three month period. Twelve patients were followed through
      their consultations with a range of health care staff at a secondary care
      Diabetes Centre and in primary care settings. A thematic analysis of the
      observation data was undertaken. RESULTS: The integrated electronic health record
      system had been implemented across the primary and secondary care interface and
      was used by many, but not all, clinicians involved in the care of patients with
      diabetes. In some areas of care it enabled health care staff to access more
      accurate and detailed information to inform their clinical decision-making.
      Issues including negotiating rules for accessing patient records and duplication
      of recording in paper record systems had not been resolved consistently across
      services. CONCLUSIONS: The findings offer suggestive evidence that a shared
      electronic health record can support more integrated care. Unresolved issues in
      implementing the system across all services and settings highlight the governance
      problems that can arise when systems are developed locally but are then extended
      across organisational and professional boundaries.

PMID- 21962436
TI  - [Radiofrequency treatment of an osteoid osteoma of the wrist: report of 2 cases].
AB  - Two cases of osteoid osteomas of the lunate and ulnar styloid process are
      described, treated by thermocoagulation. Follow-up was done clinically and by
      computed tomography (scanner) at one year, and clinically at three years. A quick
      and complete resolution of pain occurred in both cases, with bony sclerosis
      around the treated lesion on computed tomography, with no evidence of recurrence.
      A mild reduction in grip strength without functional impairment was noted in both
      cases, possibly due to a stronger controlateral dominant hand, and to a previous
      failed surgical excision in one case. No damage to neurovascular,
      musculotendinous or cutaneous structures occurred. Thermocoagulation of osteoid
      osteomas seems to be an efficient and safe technique even in critical and
      superficial anatomical regions such as the wrist.

PMID- 21962437
TI  - [Should we keep using the heating lamp in microsurgery?].
AB  - The "heating lamp" is one of the complementary measures used to improve the
      survival rate of replantations and flaps. No publication demonstrated its
      efficiency, but burn injuries have been reported. The purpose of this study was
      to estimate the efficiency of the "heating lamp". A questionnaire was sent to the
      members of the French society for surgery of the Hand, 16 % of who answered. The
      heat emitted by three electric bulbs (energy saving, strand, halogen) was
      measured at room temperature at 10, 15, 20 and 25cm distance from the bulb over
      4h. The pressure of capillary drip PFC of the pulp of the index was measured in
      10 healthy subjects by a laser Doppler. The PFC was measured without source of
      heat, then at 38, 40 and 42 degrees C, during 30min. Among the answers to the
      questionnaire, 67 % never use the heating lamp. Among the 33 % who use it, the
      protocol was variable; 18 control the temperature without precision, 18 use it
      continuously, and 23 use it more than 24hours. Nine reported complications,
      including eight burns (five flaps, three replantations). Subjectively, the
      majority of the users believe in its efficacy. Objectively, the heat emitted by
      the "heating lamp" was unimportant; whatever the distance from the source. The
      PFC did not vary with the temperature. The "heating lamp" is used empirically in
      microsurgery. The physical and physiological measures at the lower threshold for
      burns (43 degrees C) show that it is ineffective. Burns have been reported. In
      conclusion, the "heating lamp" should no longer be a part of the therapeutic
      arsenal of the hand surgeon.

PMID- 21962438
TI  - [Spontaneous rupture of extensor pollicis longus in isolated trapeziometacarpal
      arthritis].
AB  - A spontaneous rupture of the extensor pollicis longus (EPL) tendon occurred in a
      patient with trapeziometacarpal arthritis. We hypothesize that a mechanical
      attrition by protrusion at the trapeziometacarpal joint alone was responsible of
      a spontaneous rupture of the extensor pollicis longus tendon.

PMID- 21962439
TI  - PDE1 isozymes, key regulators of pathological vascular remodeling.
AB  - Pathological vascular remodeling is a hallmark of most vascular disorders such as
      atherosclerosis, postangioplasty restenosis, allograft vasculopathy, and
      pulmonary hypertension. Pathological vascular remodeling is a multi-cell
      dependent process leading to detrimental changes of vessel structure and eventual
      vessel occlusion. Cyclic nucleotide signaling regulates a variety of vascular
      functions ranging from cell contractility to cell growth. Cyclic nucleotide
      phosphodiesterases (PDEs), a large family of structurally and functionally
      distinct isozymes, regulate cyclic nucleotide levels and compartmentalization
      through catalyzing their degradation reaction. Increasing evidence has suggested
      that one of the important mechanisms for specific cyclic nucleotide regulation is
      exerted through selective activation or inhibition of distinct PDE isozymes. This
      review summarizes the work done to characterize the role and therapeutic
      potential of PDE1 isozymes in pathological vascular remodeling.

PMID- 21962441
TI  - Joining forces: feedback and integration in plant development.
AB  - Feedback and integration of information are of paramount importance for the
      robust functioning and dynamics of biological systems. In plant developmental
      biology, experimentation is increasingly combined with computational modeling to
      obtain a better understanding of how such regulatory interactions shape the
      systems' behavior. Here we highlight experimental and modeling studies on
      feedback loops and integration mechanisms involved in plant development. These
      studies have substantially expanded our understanding of previously characterized
      gene regulatory networks (GRNs). In addition, they illustrate the pervasiveness
      of regulatory interactions between seemingly unrelated processes and levels of
      organization. Modelers in plant development will increasingly face the challenges
      of what level of detail, which processes and how many levels of organization to
      incorporate when trying to understand a particular process.

PMID- 21962440
TI  - The roles of cyclic nucleotide phosphodiesterases (PDEs) in steroidogenesis.
AB  - The second messenger, cAMP, is one of the most important regulatory signals for
      control of steroidogenesis. This review focuses on current knowledge about
      regulation of cyclic nucleotides by phosphodiesterases (PDEs) in steroidogenic
      tissues. The first PDE known to directly regulate steroidogenesis was PDE2, the
      cGMP-stimulated PDE. PDE2 mediates ANP/cGMP-induced decreases in aldosterone
      production. Recently, the PDE8 family has been shown to control steroidogenesis
      in two tissues. Specifically, PDE8A regulates testosterone production by itself
      and in concert with additional IBMX-sensitive PDEs. PDE8B modulates basal
      corticosterone synthesis via acute and chronic mechanisms. In addition to cAMP
      dependent pathways, cGMP signaling also can promote steroidogenesis, and PDE5
      modulates this process. Finally, PDE mutations may lead to several human diseases
      characterized by abnormal steroid levels.

PMID- 21962443
TI  - Neural networks including microRNAs.

PMID- 21962442
TI  - Optical Coherence Tomography for live imaging of mammalian development.
AB  - Understanding the nature and mechanism of congenital defects of the different
      organ systems in humans has heavily relied on the analysis of the corresponding
      mutant phenotypes in rodent models. Optical Coherence Tomography (OCT) has
      recently emerged as a powerful tool to study early embryonic development. This
      non-invasive optical methodology does not require labeling and allows
      visualization of embryonic tissues with single cell resolution. Here, we will
      discuss how OCT can be applied for structural imaging of early mouse and rat
      embryos in static culture, cardiodynamic and blood flow analysis, and in utero
      embryonic imaging at later stages of gestation, demonstrating how OCT can be used
      to assess structural and functional birth defects in mammalian models.

PMID- 21962444
TI  - Interaction of porcine conventional dendritic cells with swine influenza virus.
AB  - Swine influenza virus (SwIV) causes sub-acute or acute respiratory infections on
      swine farms and pigs can act as "mixing vessels" for new influenza strains.
      Knowledge of the immune response of SwIV in its natural host, pigs, is very
      limited. Dendritic cells (DCs) mediate the induction of immunity to pathogens,
      but their interaction with SwIV has not been fully characterized. Thus, porcine
      bone marrow derived DCs (poBMDCs) were exposed to a circulating strain of H3N2
      SwIV in vitro. Infection of poBMDCs resulted in structures resembling influenza
      virus inside poBMDCs in vesicles and also free in cytoplasm. Viral progeny was
      undetectable in supernatant but limited replication was detected in the first 8h
      after infection. However, viral particles from infected-poBMDCs were able to
      induce cytopathic effect in susceptible cells only when cell-to-cell interaction
      was favoured. The data generated in our studies reveal the particular interaction
      of H3N2 SwIV with conventional DCs.

PMID- 21962445
TI  - Re: accuracy of hepatocellular carcinoma detection on multidetector CT in a
      transplant liver population with explant liver correlation.

PMID- 21962447
TI  - Changes of right ventricular function and longitudinal deformation in children
      with hypoplastic left heart syndrome before and after the Norwood operation.
AB  - BACKGROUND: The purpose of this study was to investigate changes in right
      ventricular (RV) function and deformation parameters before and at steady state
      after the Norwood operation in neonates with hypoplastic left heart syndrome. A
      further aim was to delineate factors that affected these changes. METHODS: On
      echocardiograms before and 21 days (range, 10-35 days) after the Norwood
      operation, the two-dimensional speckle-tracking parameters global and regional
      peak systolic longitudinal strain and strain rate were retrospectively compared
      in 33 patients with hypoplastic left heart syndrome. In addition, RV functional
      assessment included RV fractional area change and tricuspid annular plane
      systolic excursion. The associations between postoperative echocardiographic
      findings and preoperative or postoperative complications, prenatal diagnosis,
      postoperative heart rate, oxygen saturation, and medication use as well as
      cardiopulmonary bypass and aortic cross-clamp times were tested. RESULTS: Global
      strain (-18.3 +/- 3.6% vs -16.8 +/- 3.8%, P = .02) and global strain rate (-1.6
      +/- 0.3 vs -1.2 +/- 0.3 sec(-1), P < .0001) decreased significantly. Regional
      strain decreased significantly in the apical and mid lateral segments, while
      regional strain rate decreased significantly in all but the basal septal
      segments. Tricuspid annular plane systolic excursion of the lateral annulus
      decreased significantly, while RV fractional area change remained the same. No
      significant associations were found between postoperative RV function and
      potential impact factors. CONCLUSIONS: Two-dimensional global and regional
      longitudinal strain and strain rate as well as tricuspid annular plane systolic
      excursion were reduced in patients with hypoplastic left heart syndrome after the
      Norwood operation. None of the examined preoperative and postoperative patient or
      surgical factors was found to explain this decrease.

PMID- 21962446
TI  - [Weight status, dietary habits and physical activity among 6-12 year-old children
      in Castile-La Mancha].
AB  - INTRODUCTION: Childhood obesity is a multifactorial disease, in which unhealthy
      dietary patterns and sedentary lifestyles play a decisive role. The aim of this
      study was to assess the weight status, dietary habits and physical activity in
      Castile-La Mancha children. SUBJECTS AND METHODS: A cross-sectional study was
      conducted on 3061 children 6-12 years-old who were participating in the
      programme, "Alimenta su salud". Anthropometric measurements, food consumption
      frequency, dietary habits and physical activity were assessed by a questionnaire,
      including gender, age and geographical influences. RESULTS: The prevalence of
      subjects with excess weight-for-height was 24.0% and obesity was 14.3%, with
      geographical differences. Girls more often have mid-morning snacks, consume more
      supplements, and reported to be less active than boys. Special diets and sports
      activities were lower in children aged 6-9 years as compared to the 10-12 years
      old group. The intake of vegetables and fruit is low, while there is
      overconsumption of sausages, pastries, salted snacks, sweets and fast food, with
      some differences by age group. CONCLUSIONS: One out of four children is
      overweight or obese in this population. Children do not meet recommendations for
      fruit and vegetables and there is a high consumption of foods associated with
      obesity risk. Physical inactivity was more prevalent during the weekends, and
      among girls.

PMID- 21962448
TI  - Three-dimensional echocardiography in paravalvular aortic regurgitation
      assessment after transcatheter aortic valve implantation.
AB  - BACKGROUND: Paravalvular aortic regurgitation (AR) after transcatheter aortic
      valve implantation (TAVI) is common, but the evaluation of its severity by two
      dimensional (2D) transthoracic echocardiography (TTE) presents several
      constrains. The aim of this study was to assess the usefulness of a new
      methodology, using three-dimensional (3D) TTE, for better assessment of
      paravalvular AR after TAVI. METHODS: Two-dimensional and 3D TTE was performed in
      72 patients, 5 months after TAVI, using the X5-1 PureWave microbeamforming
      xMATRIX probe. The position and severity of the paravalvular AR jets were
      described using 2D and 3D TTE, and a model was designed for paravalvular AR
      systematic location description. Vena contracta width was measured using 2D
      transthoracic echocardiographic views, and the planimetry of the vena contracta
      was assessed after the perfect alignment plane was obtained using the multiplanar
      3D transthoracic echocardiographic reconstruction tool. AR volume was calculated
      as the difference between 3D TTE-derived total left ventricular stroke volume and
      right ventricular stroke volume estimated using 2D TTE. Diagnostic efficiency for
      moderate AR was assessed using receiver operating characteristic curve analysis.
      RESULTS: Forty-three patients (57.4%) presented with AR; 10 (13.3%) had central
      AR, and 33 (44.0%) had paravalvular AR jets. Vena contracta widths were similar
      between patients with moderate and mild AR (2.1 +/- 0.53 vs 1.9 +/- 0.16 mm, P =
      .16), but vena contracta planimetry was larger in patients with moderate AR than
      in those with mild AR (0.30 +/- 0.12 vs 0.09 +/- 0.07 cm(2), P = .001). Vena
      contracta planimetry on 3D TTE was better correlated with AR volume than vena
      contracta width on 2D TTE (Kendall's tau = 0.82 [P < .001] vs 0.66 [P < .001]).
      The areas under the receiver operating characteristic curves were 0.96 for vena
      contracta planimetry and 0.35 for vena contracta width. CONCLUSIONS: This study
      proposes an alternative methodology for paravalvular AR assessment after TAVI.
      Using vena contracta planimetry on 3D TTE, an accurate methodology for
      paravalvular AR jet evaluation and moderate AR classification is described.

PMID- 21962449
TI  - Improvement in the assessment of diastolic function in a clinical
      echocardiography laboratory following implementation of a quality improvement
      initiative.
AB  - BACKGROUND: The aim of this study was to demonstrate improvement in the
      characterization of diastolic function in the routine practice of a clinical
      echocardiography laboratory after the implementation of a quality improvement
      initiative. The echocardiographic analysis of left ventricular (LV) diastolic
      dysfunction is an inherently complex process involving the integration of
      multiple indices for accurate assessment. METHODS: A baseline survey of 50
      randomly chosen echocardiographic studies was reviewed for the accuracy of
      diastolic function assessment. A four-step quality improvement protocol was then
      initiated: (1) sonographer and physician education; (2) the implementation of
      data acquisition protocol changes using LV inflow, tissue Doppler velocity of the
      mitral annulus in early diastole (e'), flow propagation velocity of LV inflow
      (Vp), and left atrial volume index (LAVI), along with the establishment of
      uniform criteria for diagnostic interpretation; (3) peer review of performance;
      and (4) focused interactive case review sessions. RESULTS: At baseline,
      measurements of LV inflow were most often correct (100% accurate), while
      measurements of e' (82% accurate), Vp (12% accurate), and LAVI (12% accurate) and
      the proper classification of diastolic function (44% accurate) were significantly
      limited. After the quality improvement initiative, there were significant
      increases in the accuracy of all recorded measurements, with e' 92% accurate (a
      10% improvement; P < .10), Vp 67% accurate (a 55% improvement; P < .001), LAVI
      80% accurate (a 68% improvement, P < .001), and proper characterization of
      diastolic function 76% accurate (a 32% improvement, P < .001). CONCLUSIONS: A
      multifaceted quality improvement protocol including staff education, systematic
      support with enhanced infrastructure, and peer review with feedback can be
      effective for improving the clinical performance of a nonacademic
      echocardiography laboratory in the characterization of diastolic function.

PMID- 21962450
TI  - Evaluation of ventricular filling pressures and ventricular function by Doppler
      echocardiography in patients with functional single ventricle: correlation with
      simultaneous cardiac catheterization.
AB  - BACKGROUND: Elevated ventricular filling pressure is a marker of diastolic
      dysfunction and a known risk factor for failure of single-ventricle surgical
      palliation. Doppler echocardiography has been shown valuable in identifying
      patients with elevated ventricular end-diastolic pressure (VEDP) in other
      settings, but its utility in evaluating pediatric patients with single ventricle
      is unclear. The aim of this study was to compare Doppler parameters to
      simultaneous catheter measurements of VEDP in children with single ventricle.
      METHODS: All consecutive patients (age < 18 years) with single ventricle who
      underwent simultaneous echocardiography and catheterization in 2009 and 2010 were
      included in this prospective study. Data regarding diagnosis, morphology of the
      "single" ventricle, prior surgeries, Doppler tissue imaging (DTI),
      atrioventricular valve inflow and pulmonary vein Doppler, and myocardial
      performance index (MPI) were collected. Ventricular Doppler echocardiography was
      performed from the dominant ventricle. Simultaneous Doppler and catheter
      measurements of systolic and diastolic function and VEDP were obtained.
      Correlation of continuous variables was examined using linear regression
      analysis. Receiver operating characteristic curves, two-sample Student's t tests,
      chi(2) analyses, and Fisher's exact tests were used as appropriate. RESULTS: A
      total of 32 patients (15 male; mean age, 30.2 +/- 22 months) were studied (nine
      post-Fontan, 15 post-Glenn, and eight pre-Glenn). Mean systemic arterial
      saturation was 81 +/- 10%, mean VEDP was 11 +/- 3 mm Hg, and mean
      echocardiographically estimated ejection fraction was 55 +/- 7%. VEDP was
      correlated positively with E/E' ratio (r = 0.44, P < .01), pulmonary vein atrial
      reversal duration (r = 0.77, P < .001), and E' (r = 0.49, P < .01). Receiver
      operating characteristic curve analysis using an E/E' cutoff of 12 showed
      sensitivity of 90% (95% confidence interval, 54.1%-99.5%) and specificity of
      75.0% (95% confidence interval, 47.4%-91.7%) for identifying VEDP > 10 mm Hg.
      Single left ventricles had higher DTI S' and E' velocities and lower E/E' ratios
      and MPIs compared with single right ventricles. S' velocity correlated positively
      with ejection fraction (r = 0.77, P < .001) and negatively with single left
      ventricular MPI (r = -0.46, P < .01). CONCLUSIONS: In patients with single
      ventricle physiology, DTI and pulmonary vein Doppler echocardiographic parameters
      correlated modestly with direct measurement of VEDP and may be helpful in
      identifying patients with elevated filling pressures. In addition, single left
      ventricles had better systolic and diastolic performance than single right
      ventricles. DTI systolic velocities and left ventricular MPI correlated well with
      ventricular ejection fraction.

PMID- 21962451
TI  - Bioavailability and short-term tolerability of alendronate in glucocorticoid
      treated children.
AB  - BACKGROUND: Children receiving glucocorticoids (GCs) are at an increased risk of
      fragility fractures. Conservative measures may be inadequate in treating low bone
      mass, giving rise to fractures in this population; as such, attention has turned
      to the use of bisphosphonates. OBJECTIVE: The goal of this study was to evaluate
      the bioavailability and single-dose tolerability of alendronate (ALN) in children
      receiving a stable dose of GCs. METHODS: Children (ages 4-17 years) receiving GC
      treatment for their chronic illnesses received intravenous (125 MUg) and oral (35
      mg) ALN in a 2-period, randomized crossover study, with doses separated by at
      least a 7-day washout period. Urine was collected for either 8 or 24 hours after
      drug administration to determine urinary excretion of ALN and bioavailability.
      Tolerability was assessed by continuous collection of adverse events reported
      during the study. The main outcome measures were total urinary excretion rates,
      oral bioavailability of ALN, and adverse events. RESULTS: There were 12 patients
      in the 4- to 11-year-old group (mean age, 8.1 years; 5 girls) and 12 patients in
      the 12- to 17-year-old group (mean age, 14.3 years; 5 girls). The least-squares
      mean bioavailability (90% CI) for children aged 4 to 11 years (n = 12) was 0.43%
      (0.27-0.67) and for children aged 12 to 17 years (n = 12) it was 0.39% (0.26
      0.60). The least-squares mean bioavailability for all ages combined was 0.41%
      (0.30-0.56), with no statistical difference between the 2 age groups. The total
      urinary excretion of ALN after the intravenous dose was similar between groups.
      Fifteen patients reported a total of 36 transient clinical nonserious adverse
      events, all of which were mild or moderate in intensity; the most common were
      headache (n = 13), abdominal pain (n = 3), limb, neck, or facial pain (n = 6),
      and ankle or knee swelling (n = 3). CONCLUSIONS: The mean oral bioavailability of
      ALN was similar to previous pharmacokinetic studies in children with osteogenesis
      imperfecta and slightly lower than that observed in historical adult controls.
      Alendronate was generally well tolerated, with minor adverse events that resolved
      uneventfully. Elucidation of the full adverse-effect profile of this agent was
      limited by the single-dose nature of this study, and robust comparisons of the
      pharmacokinetics of ALN in different age groups may need a larger number of
      patients.

PMID- 21962452
TI  - Statin use and hospitalization in patients with chronic obstructive pulmonary
      disease: a nationwide population-based cohort study in Taiwan.
AB  - BACKGROUND: Statins have been widely prescribed to treat hyperlipidemia, and can
      be used for primary and secondary prevention of cardiovascular diseases. Several
      studies have shown that statins have antiinflammatory effects in addition to
      cholesterol-lowering properties. There is new evidence suggesting that statins
      have beneficial effects on patients with chronic obstructive pulmonary disease
      (COPD), which is characterized by a persistent inflammatory response. OBJECTIVE:
      The aim of this study was to determine the association between statins and COPD
      by using the Taiwan National Health Insurance database. METHODS: This was a
      nationwide population-based cohort study. A total of 6252 newly diagnosed COPD
      patients (median age, 64 years; 50.3% male) who received statins for
      hyperlipidemia treatment were identified from the 1 million sampling cohort
      dataset between January 2000 and December 2007. Another 12,469 newly diagnosed
      COPD patients (median age, 64 years; 50.3% male) who were matched for age,
      gender, and medication for COPD treatment, except for statin use, were enrolled
      as the control group. The end point of the study was hospitalization due to COPD.
      RESULTS: During an average of 4.58 (2.36) years' follow-up period, there were
      1832 patients who experienced hospitalization for COPD exacerbation (statin vs
      control = 508 [8.1%] vs 1324 [10.6%]; P = 0.001). Statin use was independently
      associated with the decreased risk of COPD hospitalization (hazard ratio, 0.66;
      95% CI, 0.60-0.74; P < 0.001). CONCLUSIONS: In the selected Taiwanese population,
      statins were associated with reduced hospitalization due to COPD in patients
      newly diagnosed with COPD, suggesting a potential beneficial effect of statins in
      patients with COPD.

PMID- 21962453
TI  - Rhein: a potential biological therapeutic drug for intervertebral disc
      degeneration.
AB  - Intervertebral disc degeneration (IDD) is regarded as an important cause of low
      back pain, which continues to be a common disability. IDD is thought to involve
      sequential changes of intervertebral disc that lead to the reduction of disc
      cells and the extracellular matrix. In addition, inflammation is crucially
      involved in IDD. Currently, there is urgent need to develop biological therapies
      for IDD that can both relieve symptoms and directly reverse the process of
      degeneration. Rhein (RH) is an anthraquinone molecule with the abilities of
      enhancing the synthesis of matrix components and inhibiting inflammatory
      response. Recently, the metabolic precursor of RH called diacerein has been
      demonstrated to have significant effects on pain relief and function improvement
      in the treatment of osteoarthritis. Given the occurrence of matrix degeneration
      and involvement of inflammation in IDD, we propose that RH might be a promising
      biological therapeutic drug for IDD due to its bioactivities. In addition, we
      hypothesize that the underlying mechanisms might be that RH has the ability to
      diminish interleukin-1 (IL-1) induced apoptosis and inhibit IL-1 induced
      secretion of MMPs and aggrecanases.

PMID- 21962454
TI  - Synthetic analogues of mycobacterial arabinogalactan linkage-disaccharide part
      II: synthesis and preliminary screening of lipophilic O-alkyl glycosides.
AB  - Lipophilic analogues of the linkage-disaccharide found in the mycobacterial cell
      wall were synthesized and the synthetic analogues when biologically evaluated
      showed promising antimycobacterial property with MIC value in the range 3.13
      12.50 MUg/mL against Mycobacterium tuberculosis H(37)Rv.

PMID- 21962455
TI  - Quantification of total iodine in intact granular starches of different botanical
      origin exposed to iodine vapor at various water activities.
AB  - Iodine has been used as an effective tool for studying both the structure and
      composition of dispersed starch and starch granules. In addition to being
      employed to assess relative amylose contents for starch samples, it has been used
      to look at the molecular mobility of the glucose polymers within intact starch
      granules based on exposure to iodine vapor equilibrated at different water
      activities. Starches of different botanical origin including corn, high amylose
      corn, waxy corn, potato, waxy potato, tapioca, wheat, rice, waxy rice, chick pea
      and mung bean were equilibrated to 0.33, 0.75, 0.97 water activities, exposed to
      iodine vapor and then absorbance spectra and LAB color were determined. In
      addition, a new iodine quantification method sensitive to <0.1% iodine (w/w) was
      employed to measure bound iodine within intact granular starch. Amylose content,
      particle size distribution of granules, and the density of the starch were also
      determined to explore whether high levels of long linear glucose chains and the
      surface area-to-volume ratio were important factors relating to the granular
      iodine binding. Results showed, in all cases, starches complexed more iodine as
      water content increased and waxy starches bound less iodine than their normal
      starch counterparts. However, much more bound iodine could be measured chemically
      with waxy starches than was expected based on colorimetric determination. Surface
      area appeared to be a factor as smaller rice and waxy rice starch granules
      complexed more iodine, while the larger potato and waxy potato granules complexed
      less than would be expected based on measured amylose contents. Corn, high
      amylose corn, and wheat, known to have starch granules with extensive surface
      pores, bound higher levels of iodine suggesting pores and channels may be an
      important factor giving iodine vapor greater access to bind within the granules.
      Exposing iodine vapor to moisture-equilibrated native starches is an effective
      tool to explore starch granule architecture.

PMID- 21962456
TI  - Altering the characteristics of a leaf litter-derived humic substance by
      adsorptive fractionation versus simulated solar irradiation.
AB  - Changes in the characteristics of a leaf litter-derived humic substance (LLHS)
      that resulted from its adsorption onto kaolinite or exposure to simulated solar
      irradiation were tracked using selected spectroscopic descriptors, apparent
      weight-average molecular weight (MW(w)) and pyrene binding. Heterogeneity within
      the original bulk LLHS was confirmed by a range of different characteristics
      obtained from ultrafiltration-based size fractions. In general, trends of some
      changing LLHS characteristics were similar for the adsorption and irradiation
      processes when tracked against percent carbon removal. For example, the overall
      values of specific ultraviolet absorbance (SUVA), MW(w), and humification index
      (HIX) all decreased with increasing irradiation time and with increasing
      concentration of mineral adsorbent in the respective experiments, indicating that
      both processes resulted in less aromatic and smaller-sized LLHS components
      remaining in solution. In addition, both the adsorption and irradiation
      experiments resulted in enrichment of the relative distribution of protein-like
      fluorescence (PLF), implying the PLF-related components had low affinities for
      phototransformation and mineral surface adsorption. Despite these apparently
      similar overall trends in LLHS characteristics caused by the adsorption and
      irradiation processes, closer examination revealed considerable differences in
      how the two processes altered the original material. Net production of
      intermediate-sized constituents was observed only with the irradiation
      experiments. In addition, residual LLHS resulting from the adsorptive
      fractionation experiments exhibited consistently higher pyrene binding versus the
      irradiated LLHS despite having comparable MW(w) values. Changes in LLHS
      characteristics due to adsorption by kaolinite were likely caused by physical
      mechanisms (primarily hydrophobic interactions between LLHS components and the
      kaolinite surface) whereas the irradiation-induced changes appear to have been
      governed by the combined effects of several alteration mechanisms, including the
      transformation of more condensed aromatic structures to less aromatic
      constituents, conformational changes resulting from selective photooxidation, and
      the photochemical disruption of intramolecular charge-transfer interactions.

PMID- 21962457
TI  - Facilitated transport of Cu with hydroxyapatite nanoparticles in saturated sand:
      effects of solution ionic strength and composition.
AB  - Column experiments were conducted to investigate the facilitated transport of Cu
      in association with hydroxyapatite nanoparticles (nHAP) in water-saturated quartz
      sand at different solution concentrations of NaCl (0-100 mM) or CaCl(2) (0.1-1.0
      mM). The experimental breakthrough curves and retention profiles of nHAP were
      well described using a mathematical model that accounted for two kinetic
      retention sites. The retention coefficients for both sites increased with the
      ionic strength (IS) of a particular salt. However, the amount of nHAP retention
      was more sensitive to increases in the concentration of divalent Ca(2+) than
      monovalent Na(+). The effluent concentration of Cu that was associated with nHAP
      decreased significantly from 2.62 to 0.17 mg L(-1) when NaCl increased from 0 to
      100 mM, and from 1.58 to 0.16 mg L(-1) when CaCl(2) increased from 0.1 to 1.0 mM.
      These trends were due to enhanced retention of nHAP with changes in IS and ionic
      composition (IC) due to compression of the double layer thickness and reduction
      of the magnitude of the zeta potentials. Results indicate that the IS and IC had
      a strong influence on the co-transport behavior of contaminants with nHAP
      nanoparticles.

PMID- 21962458
TI  - A feasibility study for a pragmatic randomised controlled trial comparing cast
      immobilisation versus no immobilisation for patients following first-time
      patellar dislocation.
AB  - BACKGROUND: The purpose of this feasibility study was to begin to determine the
      efficacy of cylinder cast immobilisation compared to no form of immobilisation
      for patients following first-time patellar dislocation (FTPD). MATERIALS AND
      METHODS: Participants were patients who attended a National Health Service
      Accident and Emergency department following a FTPD. Patients were randomised to
      receive immobilisation for four weeks in a cylinder cast followed by
      rehabilitation, versus no immobilisation and early rehabilitation. All patients
      were followed-up over a three month period, assessed using the Visual analogue
      scale for pain, Short Form-36, the Lysholm knee score and the Modified Functional
      Index. RESULTS: Forty-one patients were approached to participate. Eight
      satisfied the pre-defined eligibility criteria and were randomised between the
      two groups. Whilst the results indicated a trend for superior short-term
      functional outcomes for those patients not immobilised compared to those
      immobilised following a FTPD, the small sample and baseline imbalances between
      the groups may have had a substantial influence on the results. CONCLUSION: This
      feasibility study has indicated that the outcome measurements adopted were
      appropriate to answer this research question, but the assessment of return to
      normal activity, recurrent instability and dislocation and cost-effectiveness
      over a longer follow-up period is recommended. Similarly, defining a more
      pragmatic eligibility criteria and recruiting from multiple centres would be
      recommended for the definitive trial requiring a sample of 348 patients to
      demonstrate a statistical significant treatment effect.

PMID- 21962459
TI  - Early cognitive profiles of emergent readers: a longitudinal study.
AB  - This longitudinal study examined the contribution of phonological awareness,
      phonological memory, and visuospatial ability to reading development in 142
      English-speaking children from the start of kindergarten to the middle of Grade
      2. Partial cross-lagged analyses revealed significant relationships between early
      performance on block design and matching letter-like forms tasks and later
      reading ability. Rhyme awareness correlated with later reading ability during the
      earliest stages, but onset awareness did not emerge as important until after the
      children had started reading. Digit span correlated significantly with future
      reading ability at every stage. These findings indicate that although
      phonological awareness, phonological memory, and visuospatial ability are all
      necessary for emergent reading, their relative importance varies across the first
      2 years of reading development.

PMID- 21962460
TI  - Suppressing production of reactive oxygen species (ROS) for influenza A virus
      therapy.
AB  - Influenza A viral infections claim millions of lives worldwide and continue to
      impose a major burden on healthcare systems. Current pharmacological strategies
      to control influenza A virus-induced lung disease are problematic owing to
      antiviral resistance and the requirement for strain-specific vaccination. The
      production of reactive oxygen species (ROS), particularly superoxide, is an
      important host defence mechanism for killing invading pathogens. However,
      excessive superoxide may be detrimental following influenza A virus infection.
      Indeed, suppression of superoxide production by targeting the primary enzymatic
      source of superoxide in mammalian inflammatory cells, NADPH oxidase 2 (Nox2),
      markedly alleviates influenza A virus-induced lung injury and virus replication,
      irrespective of the infecting strain. Therefore, we propose that Nox2 oxidase
      inhibitors, in combination with current therapeutics (i.e. antivirals and
      vaccines), could be useful for suppression of influenza A virus-induced lung
      disease.

PMID- 21962461
TI  - Individual and group pelvic floor muscle training versus no treatment in female
      stress urinary incontinence: a randomized controlled pilot study.
AB  - OBJECTIVE: To compare the effects of pelvic floor muscle training (PFMT)
      performed during group treatment sessions (GT) and individual treatment sessions
      (IT) to a control group (CG) of women with stress urinary incontinence (SUI).
      HYPOTHESIS: The group treatment sessions would have better effects compared to
      individual treatment sessions. STUDY DESIGN: This randomized controlled pilot
      study included women aged over 18 years, who complained of urinary leakage on
      stress and who had not undergone physical therapy for SUI before. Forty-nine
      women were randomly allocated to the PFMT in group treatment session (GT) (n=17),
      PFMT in individual treatment session (IT) (n=17) and control group (CG) (n=15).
      The study was carried out in an outpatient physical therapy department in Sao
      Carlos, Brazil. Subjects on intervention groups were treated with the same PFMT
      protocol for 6 weeks, with two 1-h weekly sessions. The GT group carried out the
      PFMT in group treatment session and IT group in individual treatment session. The
      CG did not receive any treatment during the corresponding time. They were
      evaluated before and after treatment for primary outcome, urinary loss, and
      secondary outcomes, King's Health Questionnaire, pressure perineometry, pelvic
      floor muscle strength by digital palpation and subjective satisfaction.
      Participants, evaluator and the physical therapist were not blinded. Forty-five
      women completed the study and were included in the analysis. The statistical
      analysis was performed using Wilcoxon test for intragroup analysis and Kruskal
      Wallis and Mann-Whitney test for intergroup analysis (p<0.05). RESULTS: In
      intragroup analysis, there was a significant reduction in urinary loss measured
      by pad test only in the IT group. For primary outcome, there was a significant
      difference only after treatment between GT and CG (p<0.0001; effect size -0.91;
      95% confidence interval from 0.56 to 5.80) as well as between IT and CG
      (p<0.0001; effect size -0.90; 95% confidence interval from 0.54 to 5.84). There
      were differences after treatment in GT and IT groups for secondary outcomes:
      perineometry, muscle strength and in the domains of the quality of life
      questionnaire. For the CG group, there were not significant differences in any
      variables. In intergroup analysis for all variables, there were no differences
      between GT and IT groups. The two treated groups had similar subjective
      satisfaction (86%). There were no complaints of adverse effects due to treatment
      from either group. CONCLUSION: The results indicated similar improvement in
      clinical variables and in satisfaction with the treatment between IT and GT.

PMID- 21962462
TI  - Mechanical valve prosthesis and anticoagulation regimens in pregnancy: a tertiary
      centre experience.
AB  - OBJECTIVE: This study was undertaken to analyze the maternal and perinatal
      outcome in women with prosthetic heart valves on different anticoagulant
      regimens. STUDY DESIGN: A retrospective chart review of pregnancies in 40 women
      with mechanical valve prostheses at a tertiary referral centre from 1997 to 2010.
      The main outcome measures were major maternal complications and perinatal
      outcome. RESULTS: The valves replaced were mitral (67.5%), aortic (15.0%), or
      both (17.5%). Forty-nine pregnancies (72.1%) resulted in live births, 3(4.4%) had
      stillbirths, and 13(19.1%) had spontaneous abortions and 1(1.4%) underwent
      therapeutic abortions. The live birth rate was higher in women on heparin (78.3%)
      compared with those on warfarin (66.9%). There were 2 maternal deaths due to
      acute mitral valvular thrombosis while on acenocoumarol in the second trimester.
      Hemorrhagic complications occurred in 3 patients on heparin in the postpartum
      period, 2 of whom required transfusion. In addition one patient who was on
      acenocoumarol developed secondary hemorrhage. CONCLUSION: No anticoagulant
      regimen can be said to be entirely safe for use during pregnancy as there is a
      degree of risk with each regimen. Further larger studies are needed to come up
      with sufficient evidence-based recommendations for the best possible management
      of such patients to reduce the maternal risks after mechanical heart valve
      replacement without compromising fetal outcome.

PMID- 21962463
TI  - Use of awake oral fibreoptic intubation (AFOI) for caesarian section in a woman
      with Goldenhar Syndrome: a case report.

PMID- 21962464
TI  - Risk of spontaneous preterm delivery in a low-risk population: the impact of
      maternal febrile episodes, urinary tract infection, pneumonia and ear-nose-throat
      infections.
AB  - OBJECTIVE: To assess the associations between maternal infections during
      pregnancy (i.e. ear-nose-throat infection, pneumonia, urinary tract infection,
      febrile episodes and influenza-like infection) and spontaneous preterm delivery
      (SPTD). STUDY DESIGN: Prospective questionnaire data from the Norwegian Mother
      and Child Cohort (MoBa) study, including more than 100000 pregnancies and,
      collected during 1999-2008, were used. Linked data from the Medical Birth
      Registry of Norway were added. SPTD occurring between gestational weeks 22+0 days
      and 36+6 days was the main outcome. Data were analysed in two steps because
      questionnaires (including information about occurrence of the various infections
      so far) were completed at different stages of pregnancy. Hazard ratios (HR) were
      obtained using Cox regression. RESULTS: The SPTD proportion was low in this
      cohort: 2.9% and 2.7% at the two analysis steps, respectively. After exclusions,
      67310 and 60689 pregnancies, respectively, remained for the analyses. Ear-nose
      throat infections occurring before week 17 were associated with an increased risk
      of SPTD in the first (HR: 1.27, 95% CI: 1.08-1.50) and second (HR: 1.26, 95% CI:
      1.04-1.52) step of the analysis, but not if occurring later in pregnancy. None of
      the other maternal infections were associated with an increased risk of SPTD.
      CONCLUSION: In this low-risk population, ear-nose-throat infection in early
      pregnancy was associated with an increased risk of SPTD. However, infectious
      morbidity in later pregnancy was not. Thus, the link between maternal infection
      and preterm delivery may vary in different populations and health care settings.

PMID- 21962465
TI  - Assessment of the applicability of the Hertzian contact theory to edge-loaded
      prosthetic hip bearings.
AB  - The components of prosthetic hip bearings may experience in-vivo subluxation and
      edge loading on the acetabular socket as a result of joint laxity, causing
      abnormally high, damaging contact stresses. In this research, edge-loaded contact
      of prosthetic hips is examined analytically and experimentally in the most
      commonly used categories of material pairs. In edge-loaded ceramic-on-ceramic
      hips, the Hertzian contact theory yields accurate (conservatively, <10% error)
      predictions of the contact dimensions. Moreover, the Hertzian theory successfully
      captures slope and curvature trends in the dependence of contact patch geometry
      on the applied load. In an edge-loaded ceramic-on-metal pair, a similar degree of
      accuracy is observed in the contact patch length; however, the contact width is
      less accurately predicted due to the onset of subsurface plasticity, which is
      predicted for loads >400N. The Hertzian contact theory is shown to be ill-suited
      to edge-loaded ceramic-on-polyethylene pairs due to polyethylene's nonlinear
      material behavior. This work elucidates the methods and the accuracy of applying
      classical contact theory to edge-loaded hip bearings. The results help to define
      the applicability of the Hertzian theory to the design of new components and
      materials to better resist severe edge loading contact stresses.

PMID- 21962466
TI  - Epidemiology and burden of HPV infection and related diseases: implications for
      prevention strategies.
AB  - Human papillomavirus (HPV) infection is a necessary, although not sufficient
      cause of cervical cancer. Globally, HPV infection accounts for an estimated
      530,000 cervical cancer cases (~270,000 deaths) annually, with the majority (86%
      of cases, 88% of deaths) occurring in developing countries. Approximately 90% of
      anal cancers and a smaller subset (<50%) of other cancers (oropharyngeal, penile,
      vaginal, vulvar) are also attributed to HPV. In total, HPV accounts for 5.2% of
      the worldwide cancer burden. HPVs 16 and 18 are responsible for 70% of cervical
      cancer cases and, especially HPV 16, for a large proportion of other cancers.
      Prophylactic vaccination targeting these genotypes is therefore expected to have
      a major impact on the burden of cervical cancer as well as that of other HPV
      related cancers. Over the past 50 years, organized or opportunistic screening
      with Papanicolaou (Pap) cytology has led to major reductions in cervical cancer
      in most developed countries. However, due to lack of resources or inadequate
      infrastructure, many countries have failed to reduce cervical cancer mortality
      through screening. HPV DNA testing recently emerged as a likely candidate to
      replace Pap cytology for primary screening. It is less prone to human error and
      more sensitive than Pap in detecting high-grade cervical lesions. For countries
      with national vaccination programs, HPV testing may also serve as a low cost
      strategy to monitor long term vaccine efficacy. Introduction of well organized
      vaccination and screening programs should be a priority for all countries.
      Increased support from donors is needed to support this cause.

PMID- 21962467
TI  - Coordinating the delivery of vaccinations and other preventive health care
      recommendations for adolescents.
AB  - Although recommendations for annual preventive care for adolescents have been in
      place for decades, the need to bring adolescents to the medical setting for newly
      recommended vaccines has placed this issue in the public health spotlight.
      Aggressive efforts have been ongoing to increase adolescent adherence to new
      vaccine recommendations--a measured outcome variable, and the hope has been that
      enhanced adherence to comprehensive health care visits will follow. Evidence
      indicates that the implementation of more comprehensive preventive health care
      elements among adolescents may be improving; however, a passive approach to
      bringing more adolescents to preventive health visits using vaccine as an
      incentive may not be effective for all youth. This paper reviews the history of
      recommendations for new vaccines as well as comprehensive health care visit
      recommendations for adolescents, how these recommendations may synergistically
      improve preventive care for adolescents, and how we may need to continue to think
      creatively to further access all youth for preventive health care using
      vaccination implementation as a model for reaching out beyond the providers'
      office walls.

PMID- 21962468
TI  - Adolescent and young adult HPV vaccination in Australia: achievements and
      challenges.
AB  - Australia commenced an ongoing school based government funded human
      papillomaviruses (HPV) (cervical cancer prevention) vaccination program in April
      2007 for adolescent females aged 12-13 years. In addition, up to December 31,
      2009, a catch-up program for young females 13-26 years of age was offered: a
      school-based vaccination program was used to offer HPV vaccine to girls enrolled
      in school (14-17 years), and general practitioners or other community health
      provider offered vaccine to young women aged 18-26 years. To date, only the
      quadrivalent vaccine (HPV 6/11/16/18) has been utilized in the funded program.
      Acceptance of the vaccine is high with coverage of 3 doses of the HPV vaccine in
      the school age cohort around 70%, and just over 30% in the older age cohort.
      Since the vaccination program was initiated, a reduction in new cases of genital
      warts of 73% among vaccine eligible age females has been evidenced in STI clinics
      across Australia. A reduction of 44% of new cases in young males (not a part of
      the free program) was also documented during this same time period, suggesting
      significant herd immunity. Similarly, in the state of Victoria, a small but
      significant decrease in high grade abnormalities in Pap screening findings has
      been reported in young women<18 years for the period 2007-9, as compared to pre
      vaccination. Challenges for the future include how we can sustain and improve HPV
      vaccination coverage in young Australian women, while maintaining cervical cancer
      screening participation and reviewing cervical cancer screening methods.

PMID- 21962469
TI  - HPV-associated cancers: it's not all about the cervix.

PMID- 21962470
TI  - Genital HPV infection and related lesions in men.
AB  - Human papillomavirus (HPV) is highly prevalent in men and there is an interest in
      further understanding the relationship between HPV infection and disease in men,
      including the development of genital warts, penile intraepithelial neoplasia and
      invasive penile carcinomas. Genital warts are caused by HPV 6/11 and are the most
      common clinical manifestation of HPV in men. Though they are benign and not
      associated with mortality, they are a source of psychosocial distress and
      physical discomfort. HPV infection can also develop into invasive penile
      carcinoma which is associated with morbidity and mortality. Approximately 40% of
      invasive penile carcinomas are attributable to HPV with HPV 16, 18, and 6/11
      being the genotypes most commonly detected in penile tumors. Penile carcinomas of
      the basaloid and warty histologic subtypes are most likely to test positive for
      HPV. In addition to HPV infection, the risk factors most strongly associated with
      penile cancer are lack of neonatal circumcision, phimosis (the inability of
      uncircumcised men to fully retract the foreskin), and anogenital warts. Male
      vaccination with the quadrivalent HPV vaccine that protects against HPV
      6/11/16/18 has been shown to significantly reduce HPV-associated anogenital
      infection and disease in men. If the quadrivalent vaccine is successfully
      disseminated to large segments of the young male population, there is the
      potential for substantial reduction in genital HPV infection and related lesions
      in men.

PMID- 21962472
TI  - Widespread spread: another pitfall for ulnar sensory conduction study.

PMID- 21962471
TI  - The role of HPV in head and neck cancer and review of the HPV vaccine.
AB  - Recent data demonstrate that human papillomavirus also plays a role in cancers
      other than ano-genital cancers, specifically head and neck cancers, and non
      cancerous conditions such as recurrent respiratory papillomatosis. As more and
      more information about the role of infection in non-cervical diseases is amassed,
      additional questions about whether prophylactic human papillomavirus vaccines
      will effectively prevent these conditions are raised. This article reviews the
      epidemiology of oral human papillomavirus infection and the role of human
      papillomavirus in head and neck cancers. In addition, it will review the known
      clinical indications for human papillomavirus vaccination, and highlight other
      potential clinical targets for the vaccine that have not yet been demonstrated in
      clinical trials but for which there is biologic plausibility.

PMID- 21962473
TI  - Long term effect of local corticosteroid injection for carpal tunnel syndrome: a
      relation with electrodiagnostic severity.
AB  - OBJECTIVE: Carpal tunnel syndrome (CTS) is a common entrapment neuropathy. A
      local corticosteroid injection at the carpal tunnel inlet is often given to
      reduce the signs and symptoms. The long term effect of a local corticosteroid
      injection is not known yet. The aims of the study were to assess the long term
      effect of a local corticosteroid injection and the rognostic factors. METHODS:
      Assessment of 419 consecutive patients, seen between November 2004 and November
      2007 at our Neurology out-patient clinic. After confirmation of the diagnosis CTS
      the treating neurologist decided on the patients eligibility for a local
      corticosteroid injection, containing 40 mg methylprednisolone. RESULTS: Local
      corticosteroid injection was given to 273 of the 419 patients with CTS (65%), 122
      (29%) were treated surgically and 24 (6%) were treated by another therapy. Of the
      273 patients long term follow-up was available for 211 (77%) patients. A
      beneficial effect of more than 6 months was seen in 132 patients (63%), longer
      than 12 months in 102 patients (48%), and longer than 18 months in 71 patients
      (34%). Only severity of electrodiagnostic testing was a predictor of outcome. The
      median time until treatment failure was 15 months for mild, 5 months for moderate
      and 4.5 months for severe CTS (logrank test p=0.02). CONCLUSION: Patients with an
      electrodiagnostically mild CTS (i.e., abnormal comparative tests or prolonged
      median DSL>3.5 ms but normal median DML) are good candidates for a local steroid
      injection with 50% having a good long term effect for more than 15 months.
      SIGNIFICANCE: This study shows that the EMG severity of CTS is an important
      prognostic factor for the long term effect of a local steroid injection.

PMID- 21962475
TI  - Evaluation of hepatocellular carcinoma size using two-dimensional and volumetric
      analysis: effect on liver transplantation eligibility.
AB  - RATIONALE AND OBJECTIVES: Milan criteria recommends selection of candidates with
      hepatocellular carcinoma (HCC) for liver transplantation based on strict tumor
      size thresholds. The purpose of this study is to compare the effect of two
      dimensional and three-dimensional tumor measurements on the selection of
      candidates for liver transplantation using Milan criteria. MATERIALS AND METHODS:
      This retrospective Health Insurance Portability and Accountability Act-compliant
      study was approved by our institutional review board. Patient-informed consent
      was waived. Forty-five HCCs in 19 patients, evaluated with triphasic
      multidetector row computed tomography scans, were included in the analysis. The
      largest diameters in each two-dimensional orthogonal plane (Max2D) and within
      three-dimensional tumor boundaries (Max3D) were calculated for each lesion.
      Diameters were compared and the eligibility based on lesion size for liver
      transplantation was assessed. RESULTS: The mean Max2D diameter of HCC was 3.2 +/-
      0.9 cm and the mean Max3D diameter was 3.5 +/- 1.2 cm. There was a significant
      difference between the mean Max2D and Max3D diameters (P < .001). Among the 45
      lesions, 22 of them (48.9%) were ineligible for transplantation according to
      Max2D diameter, whereas 29 of them (64.44%) were ineligible when Max3D diameter
      was applied (P < .001). CONCLUSION: HCC diameter based on 3D measurements is
      significantly different than the conventional 2D measurements and may affect
      eligibility for liver transplantation.

PMID- 21962474
TI  - Targeting the RAS pathway in melanoma.
AB  - Metastatic melanoma is a highly lethal type of skin cancer and is often
      refractory to all traditional chemotherapeutic agents. Key insights into the
      genetic makeup of melanoma tumors have led to the development of promising
      targeted agents. An activated RAS pathway, anchored by oncogenic BRAF, appears to
      be the central motor driving melanoma proliferation. Although recent clinical
      trials have brought enormous hope to patients with melanoma, adverse effects and
      novel escape mechanisms of these inhibitors have already emerged. Definition of
      the limits of the first successful targeted therapies will provide the basis for
      further advances in management of disseminated melanoma. In this review, the
      current state of targeted therapy for melanoma is discussed, including the potent
      BRAF(V600E) inhibitor vemurafenib.

PMID- 21962476
TI  - Non-contrast enhanced MRI for evaluation of breast lesions: comparison of non
      contrast enhanced high spectral and spatial resolution (HiSS) images versus
      contrast enhanced fat-suppressed images.
AB  - RATIONALE AND OBJECTIVES: The aims of this study were to evaluate high spectral
      and spatial resolution (HiSS) magnetic resonance imaging (MRI) for the diagnosis
      of breast cancer without the injection of contrast media by comparing the
      performance of precontrast HiSS images to that of conventional contrast-enhanced,
      fat-suppressed, T1-weighted images on the basis of image quality and in the task
      of classifying benign and malignant breast lesions. MATERIALS AND METHODS: Ten
      benign and 44 malignant lesions were imaged at 1.5 T with HiSS (precontrast
      administration) and conventional fat-suppressed imaging (3-10 minutes after
      contrast administration). This set of 108 images, after randomization, was
      evaluated by three experienced radiologists blinded to the imaging technique.
      Breast Imaging Reporting and Data System morphologic criteria (lesion shape,
      lesion margin, and internal signal intensity pattern) and final assessment were
      used to measure reader performance. Image quality was evaluated on the basis of
      boundary delineation and quality of fat suppression. An overall probability of
      malignancy was assigned to each lesion for HiSS and conventional images
      separately. RESULTS: On boundary delineation and quality of fat suppression,
      precontrast HiSS scored similarly to conventional postcontrast MRI. On benign
      versus malignant lesion separation, there was no statistically significant
      difference in receiver-operating characteristic performance between HiSS and
      conventional MRI, and HiSS met a reasonable noninferiority condition.
      CONCLUSIONS: Precontrast HiSS imaging is a promising approach for showing lesion
      morphology without blooming and other artifacts caused by contrast agents. HiSS
      images could be used to guide subsequent dynamic contrast-enhanced MRI scans to
      maximize spatial and temporal resolution in suspicious regions. HiSS MRI without
      contrast agent injection may be particularly important for patients at risk for
      contrast-induced nephrogenic systemic fibrosis or allergic reactions.

PMID- 21962477
TI  - Evidence for the clinical management of chorioamnionitis.
AB  - Acute chorioamnionitis or intra-amniotic infection is defined by maternal fever
      in association with at least one additional clinical criterion including maternal
      or fetal tachycardia, maternal leukocytosis, uterine tenderness, or foul amniotic
      fluid odor. In clinically uncertain cases, the diagnosis can be augmented by
      routine laboratory studies (e.g. white blood cell count and differential count
      and acute phase reactants) and assays done on amniotic fluid. In general, the
      clinical management of chorioamnionitis is based on observational or cohort
      studies; only a few randomized controlled trials have been done. Prompt
      administration of antibiotics and delivery decrease maternal and neonatal
      morbidity. The most commonly used antibiotic regimen is ampicillin and
      gentamicin. Recent evidence supports daily rather than three-times-daily dosing
      of gentamicin for greater efficacy and decreased fetal toxicity. There is no
      evidence demonstrating harm with the administration of corticosteroids (to
      promote fetal lung maturity) in women with acute chorioamnionitis. Cesarean
      delivery should be reserved for standard obstetric indications.

PMID- 21962478
TI  - Enhanced biogas production from anaerobic codigestion of solid waste by
      sonolysis.
AB  - This paper examines the effectiveness of sonolysis in improving the anaerobic
      biodegradability of the organic fraction of municipal solid waste coming from
      mechanical selection, thus enhancing biogas production and energy recovery as
      well. Methane yield of solid organic material anaerobic digestion is
      significantly affected by substrate availability that was evaluated, in this
      investigation, through organic matter solubilisation tests carried out at
      different conditions of ultrasound treatment. Results show that sonolysis can
      significantly improve the solubilisation of organic solid waste, thus allowing
      higher biogas production from anaerobic treatment of sonicated substrates. After
      45 days, the biogas produced during anaerobic codigestion tests for the sonicated
      mixture was 24% higher than untreated one. Therefore, these results can lay the
      basis for the development of technologies useful to produce high biogas
      quantities, in order to improve clean energy generation from biowaste.

PMID- 21962479
TI  - Quantification of high-power ultrasound induced damage on potato starch granules
      using light microscopy.
AB  - A simple light microscopic technique was developed in order to quantify the
      damage inflicted by high-power low-frequency ultrasound (0-160 W, 20 kHz)
      treatment on potato starch granules in aqueous dispersions. The surface
      properties of the starch granules were modified using ethanol and SDS washing
      methods, which are known to displace proteins and lipids from the surface of the
      starch granules. The study showed that in the case of normal and ethanol-washed
      potato starch dispersions, two linear regions were observed. The number of
      defects first increased linearly with an increase in ultrasound power up to a
      threshold level. This was then followed by another linear dependence of the
      number of defects on the ultrasound power. The power threshold where the change
      over occurred was higher for the ethanol-washed potato dispersions compared to
      non-washed potato dispersions. In the case of SDS-washed potato starch, although
      the increase in defects was linear with the ultrasound power, the power threshold
      for a second linear region was not observed. These results are discussed in terms
      of the different possible mechanisms of cavitation induced-damage (hydrodynamic
      shear stresses and micro-jetting) and by taking into account the hydrophobicity
      of the starch granule surface.

PMID- 21962480
TI  - Field measurements of key parameters associated with nocturnal OBT formation in
      vegetables grown under Canadian conditions.
AB  - The objective of this study was to provide the parameter values required to model
      OBT formation in the edible parts of plants following a hypothetical accidental
      tritium release to the atmosphere at night. The parameters considered were leaf
      area index, stomatal resistance, photosynthesis rate, the photosynthetic
      production rate of starch, the nocturnal hydrolysis rate of starch, the fraction
      of starch produced daily by photosynthesis that appears in the fruits, and the
      mass of the fruit. Values of these parameters were obtained in the summer of 2002
      for lettuce, radishes and tomatoes grown under typical Canadian environmental
      conditions. Based on the maximum observed photosynthetic rate and growth rate,
      the fraction of starch translocated to the fruit was calculated to be 17% for
      tomato fruit and 14% for radish root.

PMID- 21962481
TI  - Atmospheric radionuclides transported to Fukuoka, Japan remote from the Fukushima
      Dai-ichi nuclear power complex following the nuclear accident.
AB  - Radionuclides were detected from the Fukushima nuclear accident at Fukuoka,
      Japan, 1000 km west of the Fukushima Dai-ichi nuclear power complex. Iodine-131
      was first detected 3 d after the accident, indicating that it was probably
      transported dispersively because of local meteorological conditions, and not
      global air circulation. The maximum concentrations, 5.07 mBq m(-3) for (131)I,
      4.04 mBq m(-3) for (134)Cs, and 4.12 mBq m(-3) for (137)Cs, were recorded in
      particles collected on April 6, 2011. However, these concentration levels
      decreased below the detection limit by April 26, 2011. Gaseous (131)I accounted
      for 30%-67% of the total (131)I content. The increase in dose by inhalation was
      negligible at Fukuoka.

PMID- 21962482
TI  - Effects of chronic gamma-irradiation on the aquatic microbial microcosm: equi
      dosimetric comparison with effects of heavy metals.
AB  - Effects of chronic gamma-irradiation were investigated in the aquatic microcosm
      consisting of flagellate algae Euglena gracilis as producers, ciliate protozoa
      Tetrahymena thermophila as consumers and bacteria Escherichia coli as
      decomposers. At 1.1 Gy day(-1), no effects were observed. At 5.1 Gy day(-1), cell
      densities of E. coli showed a tendency to be lower than those of controls. At 9.7
      and 24.7 Gy day(-1), population decrease was observed in E. coli. E. gracilis and
      T. thermophila died out after temporal population decrease and subsequent
      population increase in T. thermophila. It is likely that this temporal population
      increase was an indirect effect due to interspecies interactions. Effect dose
      rates of gamma-rays were compared with effect concentrations of some metals using
      the radiochemoecological conceptual model and the effect index for microcosm.
      Comparison of these community-level effects data with environmental exposure data
      suggests that ionising radiation, gadolinium and dysprosium have low risks to
      affect aquatic microbial communities while manganese, nickel and copper have
      considerable risks. Effects of chronic irradiation were smaller than those of
      acute irradiation, and an acute to chronic ratio was calculated to be 28 by
      dividing an acute dose by chronic daily dose rate at which the effect index was
      10%. This ratio would be useful for community-level extrapolation from acute to
      chronic radiation effects.

PMID- 21962483
TI  - Influence of wastewater treatment process and the population size on human virus
      profiles in wastewater.
AB  - Human adenovirus (AdV and AdV species F), enterovirus (EV) and norovirus (NoV)
      concentrations entering wastewater treatment plants (WWTP) serving different
      sized communities, and effectiveness of different treatment processes in reducing
      concentrations were established. Data was combined to create a characteristic and
      unique descriptor of the individual viral composition and termed as the sample
      virus profile. Virus profiles were generally independent of population size and
      treatment process (moving bed biofilm reactors, activated sludge, waste
      stabilisation ponds). AdV and EV concentrations in wastewater were more variable
      in small (<4000) and medium-sized (10,000-64,000) WWTP than in large-sized
      (>130,000 inhabitants) plants. AdV and EV concentrations were detected in
      influent of most WWTP (AdV range 1.00-4.08 log(10) infectious units (IU)/L, 3.25
      8.62 log(10) genome copies/L; EV range 0.7-3.52 log(10) plaque forming units
      (PFU)/L; 2.84-6.67 log(10) genome copies/L) with a reduced median concentration
      in effluent (AdV range 0.70-3.26 log(10) IU/L, 2.97-6.95 log(10) genome copies/L;
      EV range 0.7-2.15 log(10)PFU/L, 1.54-5.28 log(10) genome copies/L). Highest
      culturable AdV and EV concentrations in effluent were from a medium-sized WWTP.
      NoV was sporadic in all WWTP with GI and GII concentrations being similar in
      influent (range 2.11-4.64 and 2.19-5.46 log(10) genome copies/L) as in effluent
      (range 2.18-5.06 and 2.88-5.46 log(10) genome copies/L). Effective management of
      WWTP requires recognition that virus concentration in influent will vary -
      particularly in small and medium plants. Irrespective of treatment type,
      culturable viruses and NoV are likely to be present in non-disinfected effluent,
      with associated human health risks dependent on concentration and receiving water
      usage.

PMID- 21962484
TI  - New developments on the role of NMDA receptors in Alzheimer's disease.
AB  - Since the initial findings that NMDA receptors play important roles in cellular
      models of learning as well as neurotoxicity, abnormal function of this receptor
      has been considered a potential mechanism in the pathophysiology underlying
      Alzheimer's disease. Treatment of Alzheimer's disease with an NMDA receptor
      antagonist began several years ago, with some limited success. More recent
      mechanistic studies have examined the role of NMDA receptors in the synaptic
      effects of beta amyloid (Abeta).

PMID- 21962485
TI  - Age, scrapie status, PrP genotype and follicular dendritic cells in ovine ileal
      Peyer's patches.
AB  - Follicular dendritic cells (FDCs) residing within ileal Peyer's patches (PPs) are
      of crucial relevance for sheep scrapie early pathogenesis and subsequent scrapie
      prion neuroinvasion. In this study, ileal PP follicles were significantly more
      numerous in lambs than in adult Sarda breed sheep, with significant differences
      being also found in lymphoid follicle area, perimeter and FDC density.
      Furthermore, PrPd deposition within ileal PPs and host's PrP genotype did not
      significantly influence these parameters. We conclude that age significantly
      affects FDC density in ileal PPs from Sarda breed ovines, independently from
      host's scrapie status and PrP genotype.

PMID- 21962486
TI  - Radiation therapy for chloroma (granulocytic sarcoma).
AB  - OBJECTIVES: Chloroma (granulocytic sarcoma) is a rare, extramedullary tumor of
      immature myeloid cells related to acute nonlymphocytic leukemia or
      myelodysplastic syndrome. Radiation therapy (RT) is often used in the treatment
      of chloromas; however, modern studies of RT are lacking. We reviewed our
      experience to analyze treatment response, disease control, and toxicity
      associated with RT to develop treatment algorithm recommendations for patients
      with chloroma. PATIENTS AND METHODS: Thirty-eight patients who underwent
      treatment for chloromas at our institution between February 1990 and June 2010
      were identified and their medical records were reviewed and analyzed. RESULTS:
      The majority of patients that presented with chloroma at the time of initial
      leukemia diagnosis (78%) have not received RT because it regressed after initial
      chemotherapy. Yet most patients that relapsed or remained with chloroma after
      chemotherapy are in the RT cohort (90%). Thirty-three courses of RT were
      administered to 22 patients. Radiation subsite breakdown was: 39% head and neck,
      24% extremity, 9% spine, 9% brain, 6% genitourinary, 6% breast, 3% pelvis, and 3%
      genitourinary. Median dose was 20 (6-36) Gy. Kaplan-Meier estimates of
      progression-free survival and overall survival in the RT cohort were 39% and 43%,
      respectively, at 5 years. At a median follow-up of 11 months since RT, only 1
      patient developed progressive disease at the irradiated site and 4 patients
      developed chloromas at other sites. RT was well tolerated without significant
      acute or late effects and provided symptom relief in 95% of cases. CONCLUSIONS:
      The majority of patients with chloromas were referred for RT when there was
      extramedullary progression, marrow relapse, or rapid symptom relief required. RT
      resulted in excellent local disease control and palliation of symptoms without
      significant toxicity. We recommend irradiating chloromas to at least 20 Gy, and
      propose 24 Gy in 12 fractions as an appropriate regimen.

PMID- 21962487
TI  - Amundsen, Nansen, and the question of science: dramatizing historical research on
      the polar heroic.
AB  - Recent historical research reveals a much greater role than previously assumed
      for science in the polar activities of Fridtjof Nansen and Roald Amundsen.
      Science-based polar exploration was what first linked these two men; Amundsen's
      subsequent turn to sport and sensation dampened their relationship. These
      insights and other new perspectives about heroic period of polar exploration are
      being transformed by the author into a drama for stage that will have its world
      premier in Norway in December 2011. The play attempts to use imaginatively the
      art and craft of theatre to diffuse insight from historical scholarship.

PMID- 21962488
TI  - 'So few fat ones grow old': diet, health, and virtue in the golden age of rising
      life expectancy.
AB  - Life expectancy and chronic disease rates both rose dramatically in the United
      States during the first third of the twentieth century. As a result of this
      concurrence, Americans in this era increasingly thought about things they could
      do to extend their own lives, especially eating less, exercising more, and
      limiting stress, all factors thought to reduce chronic disease. New recognition
      of the correlation between daily physical habits and long lives made longevity
      look like a sign of virtue. At the same time, amidst discussions about the
      relationship between individual longevity and national vitality, this correlation
      also contributed to Americans' moralization of diet, exercise, and emotional self
      control.

PMID- 21962489
TI  - Using the fluorescence decay of 2-aminopurine to investigate conformational
      change in the recognition sequence of the EcoRV DNA-(adenine-N6)
      methyltransferase on enzyme binding.
AB  - The EcoRV DNA methyltransferase methylates the first adenine in the GATATC
      recognition sequence. It is presumed that methylation proceeds by a nucleotide
      flipping mechanism but no crystal structure is available to confirm this. A
      popular solution-phase assay for nucleotide flipping employs the fluorescent
      adenine analogue, 2-aminopurine (2AP), substituted at the methylation target
      site; a substantial increase in fluorescence intensity on enzyme binding
      indicates flipping. However, this appeared to fail for M.EcoRV, since 2AP
      substituted for the non-target adenine in the recognition sequence showed a much
      greater intensity increase than 2AP at the target site. This anomaly is resolved
      by recording the fluorescence decay of 2AP which shows that the target 2AP is
      indeed flipped by the enzyme, but its fluorescence is quenched by interaction
      with aromatic residues in the catalytic site, whereas bending of the duplex at
      the non-target site alleviates inter-base quenching and exposes the 2AP to
      solvent.

PMID- 21962490
TI  - [Giant hiatal hernia with pancreatic prolapse].

PMID- 21962491
TI  - Days-out-of-role associated with insomnia and comorbid conditions in the America
      Insomnia Survey.
AB  - BACKGROUND: Insomnia is highly prevalent and impairing but also highly comorbid
      with other chronic physical/mental disorders. Population-based research has yet
      to differentiate the role impairments uniquely associated with insomnia per se
      from those due to comorbidity. METHODS: A representative sample of 6791 adult
      subscribers to a large national US commercial health plan was surveyed by
      telephone about sleep and health. Twenty-one conditions previously found to be
      comorbid with insomnia were assessed with medical/pharmacy claims data and
      validated self-report scales. The Brief Insomnia Questionnaire, a fully
      structured, clinically validated scale, generated insomnia diagnoses according to
      inclusion criteria of DSM-IV-TR, ICD-10, and Research Diagnostic
      Criteria/International Classification of Sleep Disorders: Diagnostic and Coding
      Manual, Second Edition. The World Health Organization Disability Assessment
      Schedule-II assessed number of days in the past 30 when health problems prevented
      respondents from conducting their usual daily activities. Regression analyses
      estimated associations of insomnia with days-out-of-role controlling comorbidity.
      RESULTS: Insomnia was significantly associated with days-out-of-role (.90
      days/month) in a gross model. The association was reduced when controls were
      introduced for comorbidity (.42 days/month). This net association did not vary
      with number or type of comorbid conditions but was confined to respondents 35+
      years of age. Insomnia was one of the most important conditions studied not only
      at the individual level, where it was associated with among the largest mean days
      out-of-role, but also at the aggregate level, where it was associated with 13.6%
      of all days-out-of-role. CONCLUSIONS: Insomnia has a strong net association with
      days-out-of-role that does not vary as a function of comorbidity.

PMID- 21962493
TI  - Structure of myxovirus resistance protein a reveals intra- and intermolecular
      domain interactions required for the antiviral function.
AB  - Human myxovirus resistance protein 1 (MxA) is an interferon-induced dynamin-like
      GTPase that acts as a cell-autonomous host restriction factor against many viral
      pathogens including influenza viruses. To study the molecular principles of its
      antiviral activity, we determined the crystal structure of nucleotide-free MxA,
      which showed an extended three-domain architecture. The central bundle signaling
      element (BSE) connected the amino-terminal GTPase domain with the stalk via two
      hinge regions. MxA oligomerized in the crystal via the stalk and the BSE, which
      in turn interacted with the stalk of the neighboring monomer. We demonstrated
      that the intra- and intermolecular domain interplay between the BSE and stalk was
      essential for oligomerization and the antiviral function of MxA. Based on these
      results, we propose a structural model for the mechano-chemical coupling in ring
      like MxA oligomers as the principle mechanism for this unique antiviral effector
      protein.

PMID- 21962492
TI  - Evolutionarily conserved features contribute to alphabeta T cell receptor
      specificity.
AB  - alphabeta T cell receptors (TCRs) bind specifically to foreign antigens presented
      by major histocompatibility complex proteins (MHC) or MHC-like molecules.
      Accumulating evidence indicates that the germline-encoded TCR segments have
      features that promote binding to MHC and MHC-like molecules, suggesting
      coevolution between TCR and MHC molecules. Here, we assess directly the
      evolutionary conservation of alphabeta TCR specificity for MHC. Sequence
      comparisons showed that some Vbetas from distantly related jawed vertebrates
      share amino acids in their complementarity determining region 2 (CDR2). Chimeric
      TCRs containing amphibian, bony fish, or cartilaginous fish Vbetas can recognize
      antigens presented by mouse MHC class II and CD1d (an MHC-like protein), and this
      recognition is dependent upon the shared CDR2 amino acids. These results indicate
      that features of the TCR that control specificity for MHC and MHC-like molecules
      were selected early in evolution and maintained between species that last shared
      a common ancestor more than 400 million years ago.

PMID- 21962494
TI  - Simultaneous separation of hydrophobic and hydrophilic peptides with a silica
      hydride stationary phase using aqueous normal phase conditions.
AB  - The application of a silica hydride modified stationary phase with low organic
      loading has been investigated as a new type of chromatographic material suitable
      for the separation and analysis of peptides with electrospray ionization mass
      spectrometric detection. Retention maps were established to delineate the
      chromatographic characteristics of a series of peptides with physical properties
      ranging from strongly hydrophobic to very hydrophilic and encompassing a broad
      range of pI values (pI 5.5-9.4). The effects of low concentrations of two
      additives (formic acid and acetic acid) in the mobile phase were also
      investigated with respect to their contribution to separation selectivity and
      retention under comparable conditions. Significantly, strong retention of both
      the hydrophobic and the hydrophilic peptides was observed when high-organic low
      aqueous mobile phases were employed, thus providing a new avenue to achieve high
      resolution peptide separations. For example, simultaneous separation of
      hydrophobic and hydrophilic peptides was achieved under aqueous normal phase
      (ANP) chromatographic conditions with linear gradient elution procedures in a
      single run, whilst further gradient optimization enabled improved peak
      efficiencies of the more strongly retained hydrophobic and hydrophilic peptides.

PMID- 21962495
TI  - New home-made assembly for hollow-fibre membrane extraction of persistent organic
      pollutants from real world samples.
AB  - Nowadays, hollow fibre membrane extraction techniques are widely used but they
      are usually applied to water or very simple matrices such as water. In this
      paper, we propose a new assembly that allows the extraction of forty persistent
      organic pollutants in real world samples, namely orange juice, porcine plasma and
      tomatoes. The limits of detection obtained are very low even in the analysis of
      real samples (9-182 ng L(-1)). The relative standard deviations vary from 1 to
      18% and the averaged recoveries in the spike experiments are very high (65-120%)
      in the different types of samples studied. The new assembly allows a very good
      precision overcoming in one of the most important shortcomings of membrane
      extraction techniques. A central composite design has been performed to get
      optimal extraction conditions for the analytes and also the combined response of
      all the analytes has been obtained to attain the simultaneous optimum.

PMID- 21962496
TI  - Preparation of a graphene-based magnetic nanocomposite for the extraction of
      carbamate pesticides from environmental water samples.
AB  - A graphene-based magnetic nanocomposite was synthesized and used for the first
      time as an effective adsorbent for the preconcentration of the five carbamate
      pesticides (metolcarb, carbofuran, pirimicarb, isoprocarb and diethofencarb) in
      environmental water samples prior to high performance liquid chromatography-diode
      array detection. The properties of the magnetic nanocomposite were characterized
      by scanning electron microscopy and X-ray diffraction. This novel graphene-based
      magnetic nanocomposite showed great adsorptive ability towards the analytes. The
      method, which takes the advantages of both nanoparticle adsorption and magnetic
      phase separation from the sample solution, could avoid some of the time-consuming
      experimental procedures related to the traditional solid phase extraction.
      Various experimental parameters that could affect the extraction efficiencies
      have been investigated. Under the optimum conditions, the enrichment factors of
      the method for the analytes were in the range from 474 to 868. A linear response
      was achieved in the concentration range of 0.1-50 ng mL(-1). The limits of
      detection of the method at a signal to noise ratio of 3 for the pesticides were
      0.02-0.04 ng mL(-1). Compared with the dispersive liquid-liquid microextraction
      and the ultrasound-assisted surfactant-enhanced emulsification microextraction,
      much higher enrichment factors and sensitivities were achieved with the developed
      method. The method has been successfully applied for the determination of the
      carbamate pesticides in environmental water samples.

PMID- 21962497
TI  - Enhanced separation performance using a new column technology: parallel segmented
      outlet flow.
AB  - A new column technology - termed parallel segmented outlet flow was employed here
      to illustrate gains in separation performance that are achievable by the active
      management of flow as it exits from the outlet of the chromatography column.
      Parallel segmented outlet flow requires a column be fitted with an outlet fitting
      that separates flow from the central region of the column from that of wall
      region. Each region of flow is able to be processed independently, such that post
      column detection emulates end column localised detection. As a result of this
      flow segmentation and the subsequent more efficient means of detection, column
      efficiency was observed to increase by more than 20%, with gains in sensitivity
      by as much as 22%, and a decrease in peak volume by up to 85%.

PMID- 21962498
TI  - Genomics in Africa: avoiding past pitfalls.
AB  - A landmark genomics project is taking shape in Africa that shifts the power and
      prominence to local scientists. If successful, the program will offer valuable
      insights into the inheritance of common diseases and reshape the paradigm of
      foreign-funded research.

PMID- 21962499
TI  - Genomics reaches the clinic: from basic discoveries to clinical impact.
AB  - Today, more than ever, basic science research provides significant opportunities
      to advance our understanding about the genetic basis of human disease. Close
      interactions among laboratory, computational, and clinical research communities
      will be crucial to ensure that genomic discoveries advance medical science and,
      ultimately, improve human health.

PMID- 21962500
TI  - Genetics and genomics to the clinic: a long road ahead.
AB  - Advances in genomic technology have produced an explosion of new information
      about the genetic basis for human disease, fueling extraordinarily high
      expectations for improved treatments. This perspective will take brief stock of
      what genetics/genomics have brought to clinical practice to date and what we
      might expect for the future.

PMID- 21962501
TI  - Translocation mapping exposes the risky lifestyle of B cells.
AB  - Recurrent chromosomal translocations can drive oncogenesis, but how they form has
      remained elusive. Now, Chiarle et al. (2011) and Klein et al. (2011) characterize
      the genome-wide spectrum of translocations that form from a single double
      stranded break, revealing that specific loci have an intrinsic predisposition for
      frequent chromosomal rearrangements.

PMID- 21962502
TI  - Splicing up pluripotency.
AB  - In this issue of Cell, Gabut and colleagues (2011) identify a new splice variant
      of FOXP1 that directly regulates the expression of pluripotency genes. It endows
      human embryonic stem cells with their pluripotent nature and is required for the
      reprogramming of somatic cells to induced pluripotent stem cells.

PMID- 21962503
TI  - Unweaving the autism spectrum.
AB  - Although genes associated with human autism spectrum disorders have been
      identified, bridging the gap between genetics and the patchwork of behavioral
      deficits associated with the disease remains an enormous challenge. Penagarikano
      et al. (2011) now show that mice lacking CNTNAP2, a gene that causes a rare form
      of epilepsy associated with autistic features and language impairment, display
      similar phenotypes to their human counterparts, raising hopes that such models
      may speed the identification of neuronal circuitries underlying the core features
      of autism.

PMID- 21962504
TI  - A blueprint for advancing genetics-based cancer therapy.
AB  - In the era of next-generation sequencing, there are significant challenges to
      harnessing cancer genome information to develop novel therapies. Key research
      thrusts in both academia and industry will speed this transition, and lessons
      learned for cancer will more broadly shape the process for genetic contributions
      to the therapy of disease more broadly.

PMID- 21962505
TI  - Clan genomics and the complex architecture of human disease.
AB  - Human diseases are caused by alleles that encompass the full range of variant
      types, from single-nucleotide changes to copy-number variants, and these
      variations span a broad frequency spectrum, from the very rare to the common. The
      picture emerging from analysis of whole-genome sequences, the 1000 Genomes
      Project pilot studies, and targeted genomic sequencing derived from very large
      sample sizes reveals an abundance of rare and private variants. One implication
      of this realization is that recent mutation may have a greater influence on
      disease susceptibility or protection than is conferred by variations that arose
      in distant ancestors.

PMID- 21962506
TI  - Metagenomics and personalized medicine.
AB  - The microbiome is a complex community of Bacteria, Archaea, Eukarya, and viruses
      that infect humans and live in our tissues. It contributes the majority of
      genetic information to our metagenome and, consequently, influences our
      resistance and susceptibility to diseases, especially common inflammatory
      diseases, such as type 1 diabetes, ulcerative colitis, and Crohn's disease. Here
      we discuss how host-gene-microbial interactions are major determinants for the
      development of these multifactorial chronic disorders and, thus, for the
      relationship between genotype and phenotype. We also explore how genome-wide
      association studies (GWAS) on autoimmune and inflammatory diseases are uncovering
      mechanism-based subtypes for these disorders. Applying these emerging concepts
      will permit a more complete understanding of the etiologies of complex diseases
      and underpin the development of both next-generation animal models and new
      therapeutic strategies for targeting personalized disease phenotypes.

PMID- 21962507
TI  - Mapping rare and common causal alleles for complex human diseases.
AB  - Advances in genotyping and sequencing technologies have revolutionized the
      genetics of complex disease by locating rare and common variants that influence
      an individual's risk for diseases, such as diabetes, cancers, and psychiatric
      disorders. However, to capitalize on these data for prevention and therapies
      requires the identification of causal alleles and a mechanistic understanding for
      how these variants contribute to the disease. After discussing the strategies
      currently used to map variants for complex diseases, this Primer explores how
      variants may be prioritized for follow-up functional studies and the challenges
      and approaches for assessing the contributions of rare and common variants to
      disease phenotypes.

PMID- 21962508
TI  - Modeling human disease in humans: the ciliopathies.
AB  - Soon, the genetic basis of most human Mendelian diseases will be solved. The next
      challenge will be to leverage this information to uncover basic mechanisms of
      disease and develop new therapies. To understand how this transformation is
      already beginning to unfold, we focus on the ciliopathies, a class of multi-organ
      diseases caused by disruption of the primary cilium. Through a convergence of
      data involving mutant gene discovery, proteomics, and cell biology, more than a
      dozen phenotypically distinguishable conditions are now united as ciliopathies.
      Sitting at the interface between simple and complex genetic conditions, these
      diseases provide clues to the future direction of human genetics.

PMID- 21962510
TI  - Translocation-capture sequencing reveals the extent and nature of chromosomal
      rearrangements in B lymphocytes.
AB  - Chromosomal rearrangements, including translocations, require formation and
      joining of DNA double strand breaks (DSBs). These events disrupt the integrity of
      the genome and are frequently involved in producing leukemias, lymphomas and
      sarcomas. Despite the importance of these events, current understanding of their
      genesis is limited. To examine the origins of chromosomal rearrangements we
      developed Translocation Capture Sequencing (TC-Seq), a method to document
      chromosomal rearrangements genome-wide, in primary cells. We examined over
      180,000 rearrangements obtained from 400 million B lymphocytes, revealing that
      proximity between DSBs, transcriptional activity and chromosome territories are
      key determinants of genome rearrangement. Specifically, rearrangements tend to
      occur in cis and to transcribed genes. Finally, we find that activation-induced
      cytidine deaminase (AID) induces the rearrangement of many genes found as
      translocation partners in mature B cell lymphoma.

PMID- 21962511
TI  - Genome-wide translocation sequencing reveals mechanisms of chromosome breaks and
      rearrangements in B cells.
AB  - Whereas chromosomal translocations are common pathogenetic events in cancer,
      mechanisms that promote them are poorly understood. To elucidate translocation
      mechanisms in mammalian cells, we developed high-throughput, genome-wide
      translocation sequencing (HTGTS). We employed HTGTS to identify tens of thousands
      of independent translocation junctions involving fixed I-SceI meganuclease
      generated DNA double-strand breaks (DSBs) within the c-myc oncogene or IgH locus
      of B lymphocytes induced for activation-induced cytidine deaminase (AID)
      dependent IgH class switching. DSBs translocated widely across the genome but
      were preferentially targeted to transcribed chromosomal regions. Additionally,
      numerous AID-dependent and AID-independent hot spots were targeted, with the
      latter comprising mainly cryptic I-SceI targets. Comparison of translocation
      junctions with genome-wide nuclear run-ons revealed a marked association between
      transcription start sites and translocation targeting. The majority of
      translocation junctions were formed via end-joining with short microhomologies.
      Our findings have implications for diverse fields, including gene therapy and
      cancer genomics.

PMID- 21962512
TI  - A DNA repair complex functions as an Oct4/Sox2 coactivator in embryonic stem
      cells.
AB  - The transcriptional activators Oct4, Sox2, and Nanog cooperate with a wide array
      of cofactors to orchestrate an embryonic stem (ES) cell-specific gene expression
      program that forms the molecular basis of pluripotency. Here, we report using an
      unbiased in vitro transcription-biochemical complementation assay to discover a
      multisubunit stem cell coactivator complex (SCC) that is selectively required for
      the synergistic activation of the Nanog gene by Oct4 and Sox2. Purification,
      identification, and reconstitution of SCC revealed this coactivator to be the
      trimeric XPC-nucleotide excision repair complex. SCC interacts directly with Oct4
      and Sox2 and is recruited to the Nanog and Oct4 promoters as well as a majority
      of genomic regions that are occupied by Oct4 and Sox2. Depletion of SCC/XPC
      compromised both pluripotency in ES cells and somatic cell reprogramming of
      fibroblasts to induced pluripotent stem (iPS) cells. This study identifies a
      transcriptional coactivator with diversified functions in maintaining ES cell
      pluripotency and safeguarding genome integrity.

PMID- 21962513
TI  - Regulatory control of the resolution of DNA recombination intermediates during
      meiosis and mitosis.
AB  - The efficient and timely resolution of DNA recombination intermediates is
      essential for bipolar chromosome segregation. Here, we show that the specialized
      chromosome segregation patterns of meiosis and mitosis, which require the
      coordination of recombination with cell-cycle progression, are achieved by
      regulating the timing of activation of two crossover-promoting endonucleases. In
      yeast meiosis, Mus81-Mms4 and Yen1 are controlled by phosphorylation events that
      lead to their sequential activation. Mus81-Mms4 is hyperactivated by Cdc5
      mediated phosphorylation in meiosis I, generating the crossovers necessary for
      chromosome segregation. Yen1 is also tightly regulated and is activated in
      meiosis II to resolve persistent Holliday junctions. In yeast and human mitotic
      cells, a similar regulatory network restrains these nuclease activities until
      mitosis, biasing the outcome of recombination toward noncrossover products while
      also ensuring the elimination of any persistent joint molecules. Mitotic
      regulation thereby facilitates chromosome segregation while limiting the
      potential for loss of heterozygosity and sister-chromatid exchanges.

PMID- 21962514
TI  - Saturated fatty acids induce c-Src clustering within membrane subdomains, leading
      to JNK activation.
AB  - Saturated fatty acids (FA) exert adverse health effects and are more likely to
      cause insulin resistance and type 2 diabetes than unsaturated FA, some of which
      exert protective and beneficial effects. Saturated FA, but not unsaturated FA,
      activate Jun N-terminal kinase (JNK), which has been linked to obesity and
      insulin resistance in mice and humans. However, it is unknown how saturated and
      unsaturated FA are discriminated. We now demonstrate that saturated FA activate
      JNK and inhibit insulin signaling through c-Src activation. FA alter the membrane
      distribution of c-Src, causing it to partition into intracellular membrane
      subdomains, where it likely becomes activated. Conversely, unsaturated FA with
      known beneficial effects on glucose metabolism prevent c-Src membrane
      partitioning and activation, which are dependent on its myristoylation, and block
      JNK activation. Consumption of a diabetogenic high-fat diet causes the
      partitioning and activation of c-Src within detergent insoluble membrane
      subdomains of murine adipocytes.

PMID- 21962515
TI  - Conformation-sensing antibodies stabilize the oxidized form of PTP1B and inhibit
      its phosphatase activity.
AB  - Protein tyrosine phosphatase 1B (PTP1B) plays important roles in downregulation
      of insulin and leptin signaling and is an established therapeutic target for
      diabetes and obesity. PTP1B is regulated by reactive oxygen species (ROS)
      produced in response to various stimuli, including insulin. The reversibly
      oxidized form of the enzyme (PTP1B-OX) is inactive and undergoes profound
      conformational changes at the active site. We generated conformation-sensor
      antibodies, in the form of single-chain variable fragments (scFvs), that
      stabilize PTP1B-OX and thereby inhibit its phosphatase function. Expression of
      conformation-sensor scFvs as intracellular antibodies (intrabodies) enhanced
      insulin-induced tyrosyl phosphorylation of the beta subunit of the insulin
      receptor and its substrate IRS-1 and increased insulin-induced phosphorylation of
      PKB/AKT. Our data suggest that stabilization of the oxidized, inactive form of
      PTP1B with appropriate therapeutic molecules may offer a paradigm for phosphatase
      drug development.

PMID- 21962509
TI  - The Lin28/let-7 axis regulates glucose metabolism.
AB  - The let-7 tumor suppressor microRNAs are known for their regulation of oncogenes,
      while the RNA-binding proteins Lin28a/b promote malignancy by inhibiting let-7
      biogenesis. We have uncovered unexpected roles for the Lin28/let-7 pathway in
      regulating metabolism. When overexpressed in mice, both Lin28a and LIN28B promote
      an insulin-sensitized state that resists high-fat-diet induced diabetes.
      Conversely, muscle-specific loss of Lin28a or overexpression of let-7 results in
      insulin resistance and impaired glucose tolerance. These phenomena occur, in
      part, through the let-7-mediated repression of multiple components of the insulin
      PI3K-mTOR pathway, including IGF1R, INSR, and IRS2. In addition, the mTOR
      inhibitor, rapamycin, abrogates Lin28a-mediated insulin sensitivity and enhanced
      glucose uptake. Moreover, let-7 targets are enriched for genes containing SNPs
      associated with type 2 diabetes and control of fasting glucose in human genome
      wide association studies. These data establish the Lin28/let-7 pathway as a
      central regulator of mammalian glucose metabolism.

PMID- 21962516
TI  - Crystal structure of the mammalian GIRK2 K+ channel and gating regulation by G
      proteins, PIP2, and sodium.
AB  - G protein-gated K(+) channels (Kir3.1-Kir3.4) control electrical excitability in
      many different cells. Among their functions relevant to human physiology and
      disease, they regulate the heart rate and govern a wide range of neuronal
      activities. Here, we present the first crystal structures of a G protein-gated
      K(+) channel. By comparing the wild-type structure to that of a constitutively
      active mutant, we identify a global conformational change through which G
      proteins could open a G loop gate in the cytoplasmic domain. The structures of
      both channels in the absence and presence of PIP(2) suggest that G proteins open
      only the G loop gate in the absence of PIP(2), but in the presence of PIP(2) the
      G loop gate and a second inner helix gate become coupled, so that both gates
      open. We also identify a strategically located Na(+) ion-binding site, which
      would allow intracellular Na(+) to modulate GIRK channel activity. These data
      provide a structural basis for understanding multiligand regulation of GIRK
      channel gating.

PMID- 21962517
TI  - A pseudoatomic model of the dynamin polymer identifies a hydrolysis-dependent
      powerstroke.
AB  - The GTPase dynamin catalyzes membrane fission by forming a collar around the
      necks of clathrin-coated pits, but the specific structural interactions and
      conformational changes that drive this process remain a mystery. We present the
      GMPPCP-bound structures of the truncated human dynamin 1 helical polymer at 12.2
      A and a fusion protein, GG, linking human dynamin 1's catalytic G domain to its
      GTPase effector domain (GED) at 2.2 A. The structures reveal the position and
      connectivity of dynamin fragments in the assembled structure, showing that G
      domain dimers only form between tetramers in sequential rungs of the dynamin
      helix. Using chemical crosslinking, we demonstrate that dynamin tetramers are
      made of two dimers, in which the G domain of one molecule interacts in trans with
      the GED of another. Structural comparison of GG(GMPPCP) to the GG transition
      state complex identifies a hydrolysis-dependent powerstroke that may play a role
      in membrane-remodeling events necessary for fission.

PMID- 21962520
TI  - SnapShot: Human biomedical genomics.

PMID- 21962518
TI  - Beclin1 controls the levels of p53 by regulating the deubiquitination activity of
      USP10 and USP13.
AB  - Autophagy is an important intracellular catabolic mechanism that mediates the
      degradation of cytoplasmic proteins and organelles. We report a potent small
      molecule inhibitor of autophagy named "spautin-1" for specific and potent
      autophagy inhibitor-1. Spautin-1 promotes the degradation of Vps34 PI3 kinase
      complexes by inhibiting two ubiquitin-specific peptidases, USP10 and USP13, that
      target the Beclin1 subunit of Vps34 complexes. Beclin1 is a tumor suppressor and
      frequently monoallelically lost in human cancers. Interestingly, Beclin1 also
      controls the protein stabilities of USP10 and USP13 by regulating their
      deubiquitinating activities. Since USP10 mediates the deubiquitination of p53,
      regulating deubiquitination activity of USP10 and USP13 by Beclin1 provides a
      mechanism for Beclin1 to control the levels of p53. Our study provides a
      molecular mechanism involving protein deubiquitination that connects two
      important tumor suppressors, p53 and Beclin1, and a potent small molecule
      inhibitor of autophagy as a possible lead compound for developing anticancer
      drugs.

PMID- 21962521
TI  - New methodological improvements in the Microtox(r) solid phase assay.
AB  - The classic Microtox(r) solid phase assay (MSPA) based on the inhibition of light
      production of the marine bacteria recently renamed Aliivibrio fischeri suffers
      from various bias and interferences, mainly due to physico-chemical
      characteristics of the tested solid phase. To precisely assess ecotoxicity of
      sediments, we have developed an alternative method, named Microtox(r) leachate
      phase assay (MLPA), in order to measure the action of dissolved pollutants in the
      aqueous phase. Two hypotheses were formulated to explain the observed difference
      between MSPA and MLPA results: a real ecotoxicity of the solid phase or the
      fixation of bacteria to fine particles and/or organic matter. To estimate the
      latter, flow cytometry analyses were performed with two fluorochromes (known for
      their ability to stain bacterial DNA), allowing correction of MSPA measurements
      and generation of new (corrected) IC50. Comparison of results of MLPA with the
      new IC50 MSPA allows differentiating real ecotoxic and fixation effect in classic
      MSPA especially for samples with high amount of fines and/or organic matter.

PMID- 21962522
TI  - GRADE: complex decisions.

PMID- 21962519
TI  - Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core
      autism-related deficits.
AB  - Although many genes predisposing to autism spectrum disorders (ASD) have been
      identified, the biological mechanism(s) remain unclear. Mouse models based on
      human disease-causing mutations provide the potential for understanding gene
      function and novel treatment development. Here, we characterize a mouse knockout
      of the Cntnap2 gene, which is strongly associated with ASD and allied
      neurodevelopmental disorders. Cntnap2(-/-) mice show deficits in the three core
      ASD behavioral domains, as well as hyperactivity and epileptic seizures, as have
      been reported in humans with CNTNAP2 mutations. Neuropathological and
      physiological analyses of these mice before the onset of seizures reveal neuronal
      migration abnormalities, reduced number of interneurons, and abnormal neuronal
      network activity. In addition, treatment with the FDA-approved drug risperidone
      ameliorates the targeted repetitive behaviors in the mutant mice. These data
      demonstrate a functional role for CNTNAP2 in brain development and provide a new
      tool for mechanistic and therapeutic research in ASD.

PMID- 21962523
TI  - Synthesis, biological evaluation, and molecular docking studies of 1,3,4
      oxadiazole derivatives possessing 1,4-benzodioxan moiety as potential anticancer
      agents.
AB  - In present study, a series of new 1,3,4-oxadiazole derivatives containing 1,4
      benzodioxan moiety (6a-6s) as potential telomerase inhibitors were synthesized.
      The bioassay tests demonstrated that compounds 6k, 6l, 6m, 6n and 6s exhibited
      broad-spectrum antitumor activity with IC(50) concentration range from 7.21 MUM
      to 25.87 MUM against the four cancer cell lines, HEPG2, HELA, SW1116 and BGC823.
      Moreover, all the title compounds were assayed for telomerase inhibition using
      the TRAP-PCR-ELISA assay. The results showed compound 6k possessed the most
      potent telomerase activity (IC(50)=1.27 +/- 0.05 MUM). Docking simulation was
      performed to position compound 6k into the active site of telomerase (3DU6) to
      determine the probable binding model.

PMID- 21962524
TI  - Inspiration or deflation? Feeling similar or dissimilar to slim and plus-size
      models affects self-evaluation of restrained eaters.
AB  - The present studies examined the effect of perceiving images of slim and plus
      size models on restrained eaters' self-evaluation. While previous research has
      found that such images can lead to either inspiration or deflation, we argue that
      these inconsistencies can be explained by differences in perceived similarity
      with the presented model. The results of two studies (ns=52 and 99) confirmed
      this and revealed that restrained eaters with high (low) perceived similarity to
      the model showed more positive (negative) self-evaluations when they viewed a
      slim model, compared to a plus-size model. In addition, Study 2 showed that
      inducing in participants a similarities mindset led to more positive self
      evaluations after viewing a slim compared to a plus-size model, but only among
      restrained eaters with a relatively high BMI. These results are discussed in the
      context of research on social comparison processes and with regard to
      interventions for protection against the possible detrimental effects of media
      images.

PMID- 21962525
TI  - The impact of physician supply on avoidable cancer deaths in Germany. A spatial
      analysis.
AB  - BACKGROUND: Measures of avoidable deaths incorporate the notion that deaths from
      certain causes should not occur within specified age groups given effective
      prevention or timely and appropriate access to health care. The present study
      investigated the impact on specific types of avoidable cancer deaths (ACD) of
      regional variations in the supply of health services over five years using German
      districts (Kreise und kreisfreie Stadte) as units of analysis. METHODS: Age
      standardized, average ACD rates were calculated for 2000-2004 for each of the 439
      districts in Germany using unit-record mortality data. The distribution of ACD
      was subsequently analyzed using country maps and negative binomial regression
      with random intercepts. Potential endogeneity of physician supply to ACD was
      controlled for using an instrumental variable approach. The panel data for the
      years 2000-2004 were merged from a range of official statistics including
      mortality and hospital records (DESTATIS) and statistics provided by the Federal
      Office for Building and Regional Planning (INKAR). RESULTS: In women, 27.81 per
      100,000 died from preventable or treatable cancer types in an average year
      between 2000 and 2004. The rates for men were generally higher, with 40.07
      standardized ACD per 100,000. The regression results showed that an increase in
      physician supply per 100,000 was significantly associated with lower ACD rates in
      cancer of the female breast, and cancer of the colon, rectosigmoid junction,
      rectum and anus in both sexes. The contribution ranged from a decrease by a
      factor of 0.9994 (female breast cancer) to a factor of 0.9986 (cancer of the
      colon, rectosigmoid junction, rectum and anus in men) in ACD rate as the
      physician-population ratio increased by one unit. CONCLUSION: An increase in
      physician density tended to be associated with a small reduction in some ACD
      rates. We suggest that better accessibility or quality of care might have linked
      increased physician density with improved health outcomes.

PMID- 21962526
TI  - Childhood asthma and indoor allergen exposure and sensitization in Buffalo, New
      York.
AB  - This nested case-control study examined the association between prevalent asthma
      and indoor allergen sensitization and/or exposure among children (aged 5-17
      years) in Buffalo, New York. The study included a self-administered
      questionnaire, clinical interviews, skin allergen sensitivity tests and home dust
      sampling for house dust mites, cat, dog, cockroach and mouse allergens. After
      adjusting for multiple confounders, asthma cases had higher odds of being
      sensitized to Der p dust mites (odds ratio [OR]=1.94, 95% confidence interval
      (CI): 1.13-3.35), cat (OR=1.96, 95% CI: 1.13-3.39), or dog allergens (OR=1.89,
      95% CI: 1.10-3.22) than the controls. A significantly positive association
      between asthma status presence of cat allergen in the child's mattress (ORs:
      2.61, 95% CI: 1.09-6.28) was also found. Children with both sensitization and
      environmental exposure to cat allergens had higher odds of asthma (OR=7.08, 95%
      CI: 2.12-23.62) than those who were only sensitized to cat allergen (OR=2.31, 95%
      CI: 1.01-5.32) or had only home exposures (OR=1.47, 95% CI: 0.47-4.65). The
      association between allergen sensitization and asthma was more consistent than
      for home exposures. The findings help to confirm the role of allergen
      sensitization and home exposure in regard to asthma, and suggest that both,
      individually and jointly, are associated with asthma.

PMID- 21962527
TI  - Banning reproductive travel: Turkey's ART legislation and third-party assisted
      reproduction.
AB  - In March 2010, Turkey became the first country to legislate against the cross
      border travel of its citizens seeking third-party reproductive assistance.
      Although the use of donor eggs, donor spermatozoa and surrogacy had been illegal
      in Turkey since the introduction of a regulatory framework for assisted
      reproductive treatment in 1987, men and women were free to access these
      treatments in other jurisdictions. In some cases, such travel for cross-border
      reproductive care (CBRC) was even facilitated by sophisticated arrangements
      between IVF clinics in Turkey and in other countries, particularly in Cyprus.
      However, new amendments to Turkey's assisted reproduction legislation
      specifically forbid travel for the purposes of third-party assisted reproduction.
      This article outlines the cultural context of assisted reproductive treatment in
      Turkey; details the Turkish assisted reproduction legislation, particularly as it
      pertains to third-party reproductive assistance; explores Turkish attitudes
      towards donor gametes and surrogacy; assesses the existence and extent of CBRC
      prior to March 2010; and discusses some of the legal, ethical and practical
      implications of the new legislation. As CBRC becomes an increasingly pertinent
      issue, eliciting debate and discussion at both national and international levels,
      it is important to carefully consider the particular circumstances and potential
      consequences of this unique example.

PMID- 21962528
TI  - Introduction: travelling for conception and the global assisted reproduction
      market.

PMID- 21962529
TI  - Investigation of tumor suppressor genes apart from VHL on 3p by deletion mapping
      in sporadic clear cell renal cell carcinoma (cRCC).
AB  - OBJECTIVES: To investigate the most recurrent deletion loci on 3p12-p26 by
      deletion mapping studies by PCR-LOH and BAC array-FISH in sporadic conventional
      renal cell carcinoma (cRCC) and further, to evaluate the their clinicopathologic
      significance in cRCC. Comparative allelotyping studies in cRCC and major
      epithelial carcinomas (MEC) such as lung, breast, and bladder tumors were also
      carried out to investigate the specificity of the targeted loci in cRCC. SUBJECTS
      AND METHODS: A total of 40 c-RCC patients were enrolled in this study,
      categorized in to 2 groups: group I comprises of patients of stages I and II and
      group II includes patients at stages III and IV. Loss of heterozygosity (LOH)
      studies were performed by PCR using 15 microsatellite markers of region 3p12-p26
      on paired normal-tumor tissues. The recurrent LOH loci found in 27 cRCC tumors
      were further validated by BAC array-FISH using 23 serially mapped BAC clones.
      Simultaneously, the allelic deletion status of fragile histidine triad (FHIT)
      gene was studied by FISH in cRCC and major epithelial carcinoma (MEC) tumors. The
      numerical aberrations of chromosome 3 were also studied using the centromere
      enumeration probe (CEP) probe for chromosome 3 to validate the observed allelic
      losses by BAC array-FISH in cRCC as well as MECs. RESULTS: Our study revealed 3
      affected regions of LOH on 3p in cRCC: 3p12.2-p14.1, 3p14.2-p21.1, and 3p24.2
      p26.1 in both group I (stages I and II) and group II (stage III and IV).
      Comparative allelotyping studies revealed that except for LOH loci D3S2406 (20%),
      D3S1766 (14%), and D3S1560 (20%), remaining affected loci revealed retention of
      heterozygosity (ROH) in breast carcinomas. Lung and bladder tumors revealed ROH
      at all affected LOH loci. FISH with FHIT gene probe revealed deletions in cRCC
      (88%), breast (30%), and lung tumors (10%). FHIT gene deletions frequency was
      almost equal in both groups I and II (>70%), whereas a locus 3p13 (D3S2454)
      revealed the highest LOH in group II (83%) patients in comparison to group I
      (16%). BAC array-FISH studies in cRCC identified 15 recurrent deletion loci at
      crucial regions, 3p12.2, 3p14.2, 3p21.3, and 3p24.2-p26 with long continuous
      deletion of 3p14.1-p26.1 exclusively in patients of stages III and IV. Validation
      of LOH loci in breast carcinomas by BAC array-FISH with BAC clones mapped at
      these loci revealed comparatively lower deletion frequency for RP11-59E22
      (3p12.2) (30%), RP11-759B7(3p21.1) (12%), and RP11-57D6 (3p25.2, proximal to VHL)
      (15%) than cRCC. CONCLUSION: Molecular cytogenetic studies by BAC array-FISH was
      found to be more sensitive over LOH. Deletion patterns on 3p explored that
      deletion of FHIT and flanking loci may occur as an initiating event followed by
      deletions at 3p12.2, 3p21.31-3p21.32, and 3p24.2-3p26.1 in the initial stage of
      development of disease, while continuous large deletions of 3p21.3-3p26.1 and
      3p14.1-3p26.1 occur as progressive deletion due to genetic instability. Lack of
      VHL along with flanking loci in 50% cRCC patients that included both groups I and
      II supported the hypothesis of both VHL dependent and VHL independent pathways in
      cRCC tumorigenesis. Comparative allelotyping studies in cRCC and MECs indicated
      association of specific targeted loci including VHL in cRCC. Further expansion of
      these studies with characterization of the genes at targeted loci and correlation
      with clinical outcome will explore the prognostic significance and also provide
      an insight into the mechanisms of tumor suppressive pathways in genitourinary
      cancers such as CRCC.

PMID- 21962530
TI  - Fat grafting accelerates revascularisation and decreases fibrosis following
      thermal injury.
AB  - BACKGROUND: Fat grafting has been shown clinically to improve the quality of burn
      scars. To date, no study has explored the mechanism of this effect. We aimed to
      do so by combining our murine model of fat grafting with a previously described
      murine model of thermal injury. METHODS: Wild-type FVB mice (n=20) were
      anaesthetised, shaved and depilitated. Brass rods were heated to 100 degrees C in
      a hot water bath before being applied to the dorsum of the mice for 10s, yielding
      a full-thickness injury. Following a 2-week recovery period, the mice underwent
      Doppler scanning before being fat/sham grafted with 1.5cc of human fat/saline.
      Half were sacrificed 4 weeks following grafting, and half were sacrificed 8 weeks
      following grafting. Both groups underwent repeat Doppler scanning immediately
      prior to sacrifice. Burn scar samples were taken following sacrifice at both time
      points for protein quantification, CD31 staining and Picrosirius red staining.
      RESULTS: Doppler scanning demonstrated significantly greater flux in fat-grafted
      animals than saline-grafted animals at 4 weeks (fat=305+/-15.77mV, saline=242+/
      15.83mV; p=0.026). Enzyme-linked immunosorbent assay (ELISA) analysis in fat
      grafted animals demonstrated significant increase in vasculogenic proteins at 4
      weeks (vascular endothelial growth factor (VEGF): fat=74.3+/-4.39ngml(-1),
      saline=34.3+/-5.23ngml(-1); p=0.004) (stromal cell-derived factor-1 (SDF-1):
      fat=51.8+/-1.23ngml(-1), saline grafted=10.2+/-3.22ngml(-1); p<0.001) and
      significant decreases in fibrotic markers at 8 weeks (transforming growth factor
      beta1(TGF-beta): saline=9.30+/-0.93, fat=4.63+/-0.38ngml(-1); p=0.002) (matrix
      metallopeptidase 9 (MMP9): saline=13.05+/-1.21ngml(-1), fat=6.83+/-1.39ngml(-1);
      p=0.010). CD31 staining demonstrated significantly up-regulated vascularity at 4
      weeks in fat-grafted animals (fat=30.8+/-3.39 vessels per high power field (hpf),
      saline=20.0+/-0.91 vessels per high power field (hpf); p=0.029). Sirius red
      staining demonstrated significantly reduced scar index in fat-grafted animals at
      8 weeks (fat=0.69+/-0.10, saline=2.03+/-0.53; p=0.046). CONCLUSIONS: Fat grafting
      resulted in more rapid revascularisation at the burn site as measured by laser
      Doppler flow, CD31 staining and chemical markers of angiogenesis. In turn, this
      resulted in decreased fibrosis as measured by Sirius red staining and chemical
      markers.

PMID- 21962532
TI  - Beneficial effects of ventromedial hypothalamus (VMH) lesioning on function and
      morphology of the liver after hepatectomy in rats.
AB  - Liver has a high regenerative capacity and restores its mass and function shortly
      after partial hepatectomy through increased proliferation and metabolic
      modification of hepatocytes. The proliferation of hepatocytes can be triggered by
      its mass reduction after hepatectomy or by the neural factors including lesioning
      of the ventromedial hypothalamus (VMH). In the present study, we examined the
      effect of VMH lesioning on liver regeneration in hepatectomized rats by
      evaluating liver function and morphology. We found that functional deficits
      caused by partial hepatectomy [prolonged prothrombin time (PT), increased
      indocyanine green (ICG) retention, and decrease in PAS (periodic Acid-Schiff
      staining)-positive hepatocytes] were restored by VMH lesioning at 1 week after
      the surgery, whereas these alterations disappeared at 4 weeks. Morphologically,
      lipid microdroplets, which are considered to be important for maintaining
      contiguous liver function via supplying fuel for cell proliferation, were found
      to accumulate in hepatocytes of the hepatectomized rats at early period (1 day)
      after partial hepatectomy. Interestingly, such lipid microdroplets were also
      detected in the VMH lesioned rats and the more abundantly in the VMH lesioned,
      hepatectomized rats up to 1 week after the surgery. In conclusion, our results
      suggest that VMH lesioning in rats promotes recovery of liver anatomically and
      functionally after partial hepatectomy by promoting cell proliferation process.

PMID- 21962533
TI  - The distribution of beta-tubulin isotypes in cultured neurons from embryonic,
      newborn, and adult mouse brains.
AB  - Tubulin, the subunit protein of microtubules, is an alpha/beta heterodimer. Both
      alpha- and beta-tubulin exist as numerous isotypes, differing in their amino acid
      sequences and encoded by different genes. The differences are highly conserved in
      evolution, suggesting that they are functionally significant. Neurons are a
      potentially very useful system for elucidating this significance, because they
      are highly differentiated cells and rich in tubulin isotypes. We have examined
      the distribution of beta-tubulin isotypes in mouse primary cultured cortical
      neurons from embryonic fetus, newborn pups and adults. Neurons from both
      embryonic and adult mouse brains express the betaI, betaII, and betaIII isotypes,
      but apparently not betaIV or betaV. betaI, betaII, and betaIII are found in both
      cell bodies and neurites. However, the situation is different in newborn mice.
      Although betaI and betaIII are present in these neurons in both cell bodies and
      neurites and betaIV is absent, just like in embryonic and adult mice, two
      striking differences were noted in the neurons from newborn mice. First, betaV is
      apparently present evanescently in the neurons in both cell bodies and neurites.
      Interestingly, the betaV was expressed strongly in newborn neurons after one day
      of culture; expression became much weaker after 3days, and almost disappeared
      after 5days. Second, the distribution of betaII is different from other isotypes.
      After newborn mouse neurons were cultured for 3days, betaII started to disappear
      partly from the cell bodies; this was much more pronounced after five days in
      culture. Our findings suggest that betaII's major function may involve the
      neurites and not the cell body. They also raise the possibility that betaV has a
      unique role in the neurons of newborn mice.

PMID- 21962534
TI  - Basic dye adsorption onto an agro-based waste material--sesame hull (Sesamum
      indicum L.).
AB  - The aim of this project was to establish an economical and environmentally benign
      biotechnology for removing methylene blue (MB) from wastewater. The adsorption
      process of MB onto abandoned sesame hull (Sesamum indicum L.) (SH) was
      investigated in a batch system. The results showed that a wide range of pH (3.54
      10.50) was favorable for the adsorption of MB onto SH. The Langmuir model
      displayed the best fit for the isothermal data. The exothermic adsorption process
      fits a pseudo-second-order kinetic model. The maximum monolayer adsorption
      capacity (359.88 mg g(-1)) was higher than most previously investigated low-cost
      bioadsorbents (e.g., peanut hull, wheat straw, etc.). This study indicated that
      sesame hull is a promising, unconventional, affordable and environmentally
      friendly bio-measure that is easily deployed for removing high levels of MB from
      wastewater.

PMID- 21962531
TI  - Sleep loss alters synaptic and intrinsic neuronal properties in mouse prefrontal
      cortex.
AB  - Despite sleep-loss-induced cognitive deficits, little is known about the cellular
      adaptations that occur with sleep loss. We used brain slices obtained from mice
      that were sleep deprived for 8h to examine the electrophysiological effects of
      sleep deprivation (SD). We employed a modified pedestal (flowerpot) over water
      method for SD that eliminated rapid eye movement sleep and greatly reduced non
      rapid eye movement sleep. In layer V/VI pyramidal cells of the medial prefrontal
      cortex, miniature excitatory post synaptic current amplitude was slightly
      reduced, miniature inhibitory post synaptic currents were unaffected, and
      intrinsic membrane excitability was increased after SD.

PMID- 21962535
TI  - Distribution of C and N in soluble fractionations for characterizing the
      respective biodegradation of sludge and bulking agents.
AB  - This study utilized C and N distribution in different soluble fractionations
      instead of the routine C/N ratio to characterize the respective biodegradation of
      sludge and bulking agents in bio-drying or composting. For sludge, C was mainly
      distributed (31.8%) in the neutral detergent soluble and water insoluble fraction
      (SOL), whereas it was mainly distributed in the cellulose-like fraction (CEL) for
      straw (39.5%) and sawdust (45.8%). A large proportion of N was in the 35  degrees
      C water-soluble fraction (W35  degrees C) for sludge (34.0%) and straw (52.5%),
      while for sawdust it was in the lignin-like fraction (LIG; 49.4%). For sludge,
      the C and N loss were mainly contributed by W35  degrees C (36.9% and 52.4%). The
      other fractions also contributed a lot. For straw, 22.4% of C and 89.8% of N lose
      in W35  degrees C. The hemicellulose-like (HEM) and CEL fraction also gave a
      large contribution to C loss (28.5% and 40.1%), while contributing little to N
      loss.

PMID- 21962536
TI  - Anaerobic submerged membrane bioreactor (AnSMBR) for municipal wastewater
      treatment under mesophilic and psychrophilic temperature conditions.
AB  - A pilot scale anaerobic submerged membrane bioreactor (AnSMBR) with an external
      filtration unit for municipal wastewater treatment was operated for 100 days.
      Besides gas sparging, additional shear was created by circulating sludge to
      control membrane fouling. During the first 69 days, the reactor was operated
      under mesophilic temperature conditions. Afterwards, the temperature was
      gradually reduced to 20  degrees C. A slow and linear increase in the filtration
      resistance was observed under critical flux conditions (7 L/(m2 h)) at 35 
      degrees C. However, an increase in the fouling rate probably linked to an
      accumulation of solids, a higher viscosity and soluble COD concentrations in the
      reactor was observed at 20  degrees C. The COD removal efficiency was close to
      90% under both temperature ranges. Effluent COD and BOD5 concentrations were
      lower than 80 and 25 mg/L, respectively. Pathogen indicator microorganisms (fecal
      coliforms bacteria) were reduced by log(10)5. Hence, the effluent could be used
      for irrigation purposes in agriculture.

PMID- 21962537
TI  - A consolidated bio-processing of ethanol from cassava pulp accompanied by
      hydrogen production.
AB  - A biphasic fermentation approach was undertaken for the production of ethanol and
      hydrogen from cassava pulp. The glucose generated by co-culture of Clostridium
      thermocellum and Thermoanaerobacterium aotearoense was 13.65+/-0.45 g L(-1),
      which was 1.75 and 1.17-fold greater than that produced by mono-cultures of C.
      thermocellum and T. aotearoense, respectively. The accumulated glucose could be
      utilised rapidly by subsequently inoculated Saccharomyces cerevisiae. An inoculum
      ratio of 1:1, a thermophilic fermentation of 84 h, and a pulp concentration of 4%
      proved optimal for ethanol production, fermentation efficiency, and productivity.
      With these conditions, the ethanol level reached 8.83+/-0.31 g L(-1) with a
      fermentation efficiency of 64.95+/-2.71%. Hydrogen production of 4.06 mmol by the
      co-culture system was 1.54 and 2.09-fold greater than that produced by mono
      cultures of C. thermocellum and T. aotearoense, respectively. This sequential co
      culture approach provided a consolidated bio-processing means to produce ethanol
      and hydrogen from cassava pulp.

PMID- 21962538
TI  - Enantioselective effects of alpha-hexachlorocyclohexane (HCH) isomers on androgen
      receptor activity in vitro.
AB  - Alpha-hexachlorocyclohexane (alpha-HCH), a part of the HCH pesticide mixture, is
      one of the most widespread persistent organic pollutants. Interestingly, only
      limited number of studies addressed the toxicity of alpha-HCH and the effects of
      its individual optical isomers have not been investigated in detail. In the
      present study we separated two alpha-HCH enantiomers by preparative HPLC and
      studied their activities towards androgen receptor (AR) using the MDA-kb2 cell
      line stably transfected with the luciferase reporter gene under the control of
      AR. There was no direct effect of alpha-HCH on AR but both isomers significantly
      suppressed the activity of AR in co-exposure with the natural ligand
      dihydrotestosterone in a concentration-dependent manner. One of the enantiomers
      appeared to be more active at lower concentration, which was also supported by
      the molecular modeling calculations with AR that showed a slight difference in
      estimated free energy of binding and inhibition constant between two enantiomers.
      Although studies with other pesticides demonstrated strong enantioselective
      differences in toxicity, the present research shows rather minor differences in
      modulations of AR by both alpha-HCH enantiomers. For the first time,
      enantioselective effects of alpha-HCH were demonstrated and the results suggest
      interaction with multiple regulatory events controlling the AR activity. Full
      elucidation of the toxicity mechanism will require further research.

PMID- 21962539
TI  - Long-term nutrition support in gastrointestinal disease--a systematic review of
      the evidence.
AB  - OBJECTIVES: Patients with gastrointestinal disease or those having undergone
      gastrointestinal surgery are often at nutritional risk for extended periods after
      they are discharged from the acute care setting. This systematic review aims to
      assess the evidence for the use of oral nutrition support, in the form of oral
      nutrition supplementation or individualized dietary advice in people with
      gastrointestinal illness, for a prolonged period of time, deemed greater than 2
      mo. METHODS: A systematic review of relevant databases was conducted from January
      1980 until December 2009. Suitable articles were appraised looking at oral
      nutrition support, for greater than 2 mo, and the association with nutritional
      outcomes in people with gastrointestinal illness. RESULTS: Six studies were
      identified for this systematic review. The range of patient groups,
      interventions, and outcomes differed between studies. Overall evidence supports
      the use of oral nutrition support for improving outcomes such as weight,
      function, caloric intake, and quality of life. There was a trend toward improved
      outcomes with individualized dietary advice as the study period increased.
      CONCLUSIONS: There is strong evidence to support the use of oral nutrition
      support in a long-term setting for gastrointestinal patients. It appears that as
      the timeframe increases, there may be a greater role for the use of
      individualized dietary advice over oral nutrition supplementation alone. However,
      more research is needed in this area.

PMID- 21962540
TI  - [Intra-uterine insemination outcomes according to the serum AMH level on day 3].
AB  - The aim of this retrospective study was to compare the IUI outcomes according to
      serum antiMullerian hormone (AMH) levels on day 3 of cycle. PATIENTS AND METHOD:
      Three hundred and sixteen patients undergoing their first IUI cycle after a serum
      AMH level test in our laboratory. These patients were less than 39 years of age
      and the number of motile spermatozoa inseminated (NMSI) was superior or equal to
      five millions. Patients were divided in three groups according to their serum AMH
      level: the group 1 with AMH level less than 1ng/ml, the group 2 with AMH level
      between 1 and 4.5ng/ml, and the group 3 with AMH level greater than 4.5ng/ml.
      MAIN OUTCOMES MEASURE(S): clinical pregnancy rate and ongoing pregnancy rate per
      IUI cycle. RESULT(S): No statistical difference has been observed on follicle
      stimulation, number of mature follicle, oestradiol level on day hCG, clinical
      pregnancy rate, spontaneous abortion. The ongoing pregnancy rate per IUI
      practised were respectively: 15.5% for AMH inferior to 1ng/ml versus 15.2% for
      AMH between 1 to 4.5ng/ml and versus 13.6% for AMH superior to 4.5ng/ml.
      CONCLUSION(S): AMH value does not seem to have an impact on the IUI outcomes and
      particularly on the pregnancy rates.

PMID- 21962541
TI  - Characterization of bonding between poly(dimethylsiloxane) and cyclic olefin
      copolymer using corona discharge induced grafting polymerization.
AB  - Thermoplastics have been increasingly used for fabricating microfluidic devices
      because of their low cost, mechanical/biocompatible attributes, and well
      established manufacturing processes. However, there is sometimes a need to
      integrate such a device with components made from other materials such as
      polydimethylsiloxane (PDMS). Bonding thermoplastics with PDMS to produce hybrid
      devices is not straightforward. We have reported our method to modify the surface
      property of a cyclic olefin copolymer (COC) substrate by using corona discharge
      and grafting polymerization of 3-(trimethoxysilyl)propyl methacrylate; the
      modified surface enabled strong bonding of COC with PDMS. In this paper, we
      report our studies on the surface modification mechanism using attenuated total
      reflectance Fourier transform infrared spectroscopy (ATR-FTIR), X-ray
      photoelectron spectroscopy (XPS), atomic force microscopy (AFM) and contact angle
      measurement. Using this bonding method, we fabricated a three-layer
      (COC/PDMS/COC) hybrid device consisting of elastomer-based valve arrays. The
      microvalve operation was confirmed through the displacement of a dye solution in
      a fluidic channel when the elastomer membrane was pneumatically actuated. Valve
      enabled microfluidic handling was demonstrated.

PMID- 21962542
TI  - A general method to determine ionization constants of responsive polymer thin
      films.
AB  - A general method has been developed to determine the ionization constants of
      polymer thin films based on the stimuli-responsiveness of the polymer. Robust
      polymer films were fabricated on silicon wafers and gold slides using
      perfluorophenyl azide (PFPA) as the coupling agent. The ionization constants were
      measured by a number of techniques including ellipsometry, dynamic contact angle
      goniometry, and surface plasmon resonance imaging (SPRi). Using poly(4
      vinylpyridine) (P4VP) as the model system, P4VP thin films were fabricated and
      the ionization constants of the films were measured taking advantage of the pH
      responsive property of the polymer. The pK(a) determined by ellipsometry, ~4.0,
      reflects the swelling of the polymer film in response to pH. The pK(a) value
      calculated from the dynamic contact angle measurements, ~5.0, relies on the
      change in hydrophilicity/hydrophobicity of the films as the polymer undergoes
      protonation/deprotonation. The pK(a) value measured by SPRi, ~4.9, monitors in
      situ the change of refractive index of the polymer thin film as it swells upon
      protonation. This was the first example where SPRi was used to measure the
      ionization constants of polymers.

PMID- 21962543
TI  - Mitoxantrone-loaded zeolite beta nanoparticles: preparation, physico-chemical
      characterization and biological evaluation.
AB  - This article describes the preparation and the physico-chemical characterization
      of a new host-guest system consisting of zeolite beta nanoparticles as host and
      mitoxantrone as guest. The resulting host-guest system mitoxantrone@beta is
      characterized in terms of morphology (transmission electron microscopy, dynamic
      light scattering), structure (powder wide-angle X-ray diffraction, nitrogen
      sorption), surface charge (xi-potential measurements), and optical properties (UV
      visible absorption, steady-state fluorescence). Mitoxantrone@beta particles are
      monodisperse in size with a mean diameter centered around 100 nm. Mitoxantrone
      guest molecules are adsorbed at the micropore entrances of zeolite host.
      Resulting nanoparticles retrieve the interesting optical properties of guest
      molecules with a fluorescence emission band in the near-infrared region.
      Mitoxantrone loading is comparatively evaluated by three different means
      (elemental analysis, direct and indirect UV-visible absorption studies) showing a
      loading level of 6.8 MUmol/g. Mitoxantrone@beta nanoparticles also show a
      noticeable cytotoxic effect when applied to cancer cells.

PMID- 21962544
TI  - Massive right atrial myxoma: an unusual presentation in an elderly patient.
AB  - Primary heart tumors are rare with an estimated incidence ranging 0.0017-0.19%.
      Myxoma is the most prevalent primary heart tumor. The right atrium is an unusual
      location, occurring only in the 15-20% of myxoma cases. We describe the case of a
      massive right atrial myxoma causing right ventricular inflow and tricuspid valve
      obstruction. The tumor was detected by echocardiography and confirmed by abdomen
      thoracic tomography. It was resected along with a section of tricuspid septal
      leaflet, followed by primary repair. In 2-year follow-up the patient is
      asymptomatic.

PMID- 21962545
TI  - The analysis of aging and elderly age quality in empirical research: data based
      on University of the Third Age (U3A) students.
AB  - The aim of the study was to evaluate aging and elderly age quality in elderly
      individuals and persons entering the elderly age participating U3A continuous
      education courses. The research included 255 students of the U3A located in
      Bydgoszcz, Poland. The research included 235 women and 20 men of mean age 64.43
      years. The dominant group was persons with secondary education (65.9%), and
      higher education (28.2%) as well as married (54.5%). All of the subjects included
      in the study were fully mobile. The study was conducted based on authors'
      original questionnaire which consisted of 24 questions and a basic personal data
      form surveying age, gender, marital status, level of education as well as self
      reported illnesses and health problems. The research assumed the majority of
      positive responses as the sign of happy aging and experiencing one's own old age.
      Positive correlation was observed between the statement that human beings
      influence quality and shape of their lives, and therefore they are responsible
      for their own life. The higher the level of fulfilling aims in life the more
      frequently elderly age was perceived as a happy period. In the research data
      there was a relationship observed between levels of education and discrimination,
      i.e., the higher level of education the fewer cases of discrimination
      experienced: chi(2)=12.992 (df=2; p<0.01). Moreover, a very weak correlation was
      observed between marital status and a sense or absence of sense of emptiness in
      life rho=0.128; p<0.05. The most appreciated values in life, according to the
      subjects were health, happiness in family and mental efficiency. The biggest
      worries concerned serious diseases and being dependent on other people. Most
      often indicated ways to lead happy elderly life were being active and open to
      people as well as showing optimistic attitude. The research, which was conducted
      on a relatively large group of people (n=255), proves positive aging direction
      among the elderly and persons entering late adulthood period who attend
      continuous education courses at U3A.

PMID- 21962547
TI  - Truth telling in clinical practice.

PMID- 21962546
TI  - Incidental findings at chest CT: a needs assessment survey of radiologists'
      knowledge.
AB  - RATIONALE AND OBJECTIVES: To assess practice patterns in evaluating incidental
      findings at chest computed tomography (CT) to determine the need for further
      education. MATERIALS AND METHODS: A survey was given to 1600 radiologists,
      presenting four clinical case questions regarding the evaluation/significance of
      the following incidental findings at chest CT: thyroid lesion; enlarged
      mediastinal lymph nodes; asymptomatic, small pulmonary embolus; and small lung
      nodule. The respondents' answers were compared with "truth," as defined by the
      best evidence available in the medical literature. Additional questions elicited
      the respondents' demographics and comfort levels in addressing the findings.
      Analysis of variance models with a Tukey correction for post hoc comparisons and
      chi-square tests were used to determine if any demographic factors or comfort
      levels were predictive of higher correct response rates. RESULTS: The overall
      survey response rate was 28% (445/1600). Correct case response rates ranged from
      26% (115/442) to 79% (343/445). Only 6% (28/438) of respondents chose the correct
      answers for all cases. Up to 80% (353/440) of respondents felt comfortable in
      addressing findings, and only 57% (252/443) of respondents felt that they needed
      more training in this area. Fellowship training in cardiothoracic radiology,
      working in a teaching practice, and subspecialization in abdominal or
      cardiothoracic radiology were predictive of higher correct response rates. Except
      for one case question, the comfort level was not predictive of correct response
      rate. CONCLUSIONS: There was considerable variability among radiologists and
      substantial deviation from best medical practice with regard to the
      interpretation/evaluation of incidental findings at chest CT, signifying a
      significant need for further education.

PMID- 21962548
TI  - Five reasons to fund the Global Fund.

PMID- 21962549
TI  - US National Cancer Act: 40 years on.

PMID- 21962551
TI  - Duration of isoniazid preventive therapy in HIV-infected patients.

PMID- 21962553
TI  - Duration of isoniazid preventive therapy in HIV-infected patients.

PMID- 21962554
TI  - Addressing Mississippi's HIV/AIDS crisis.

PMID- 21962555
TI  - Sex-selected abortion in India.

PMID- 21962556
TI  - Time for a boycott of Chinese science and medicine pertaining to organ
      transplantation.

PMID- 21962557
TI  - A rare cause of gait ataxia.

PMID- 21962558
TI  - [Histological analysis of dental follicles after unerupted mandibular third molar
      extraction].
AB  - INTRODUCTION: The extraction of third mandibular tooth germ (M3) is often
      prophylactic to avoid orthodontic treatment relapse and to prevent infectious or
      tumoral diseases developing from the dental sac. The purpose of this study was to
      screen for early histopathological modification of dental follicles
      (inflammatory, infiltration, or epithelial metaplasia) after extraction of third
      mandibular tooth germ (M3) on asymptomatic patients. The secondary objective was
      to study the proliferative activity of the epithelium by dosing the anti Ki-67
      antibody. PATIENTS AND METHOD: Twenty dental follicles extracted from 12 boys and
      eight girls between 14 and 18 years of age were examined under phototonic
      microscopy. The proliferative activity of the epithelium was assessed by immuno
      histochemistry. RESULTS: Three dental follicles presented with focal epidermoid
      metaplasia of the epithelium, without odontogenic tumoral proliferation. In all
      other cases, the cylindrical epithelial cell structure was normal. A mild chronic
      inflammatory infiltrate was present in 30% of the cases. Immuno-histochemical
      analysis revealed labeling of very rare epithelial lining cells, slightly more in
      cases presenting with metaplasia. DISCUSSION: The prevalence of early
      morphological changes of dental sac is low. This histo-morphological study does
      not support the systematic extraction of asymptomatic mandibular tooth germs
      (M3).

PMID- 21962559
TI  - Gross CO2 and CH4 emissions from the Nam Ngum and Nam Leuk sub-tropical
      reservoirs in Lao PDR.
AB  - Gross CO2 and CH4 emissions (degassing and diffusion from the reservoir) and the
      carbon balance were assessed in 2009-2010 in two Southeast Asian sub-tropical
      reservoirs: the Nam Ngum and Nam Leuk Reservoirs (Lao PDR). These two reservoirs
      are within the same climatic area but differ mainly in age, size, residence time
      and initial biomass stock. The Nam Leuk Reservoir was impounded in 1999 after
      partial vegetation clearance and burning. However, GHG emissions are still
      significant 10 years after impoundment. CH4 diffusive flux ranged from 0.8
      (January 2010) to 11.9 mmol m(-2) d(-1) (April 2009) and CO2 diffusive flux
      ranged from -10.6 (October 2009) to 38.2 mmol m(-2) d(-1) (April 2009). These
      values are comparable to other tropical reservoirs. Moreover, degassing fluxes at
      the outlet of the powerhouse downstream of the turbines were very low. The
      tentative annual carbon balance calculation indicates that this reservoir was a
      carbon source with an annual carbon export (atmosphere+downstream river) of about
      2.2+/-1.0 GgC yr(-1). The Nam Ngum Reservoir was impounded in 1971 without any
      significant biomass removal. Diffusive and degassing CO2 and CH4 fluxes were
      lower than for other tropical reservoirs. Particularly, CO2 diffusive fluxes were
      always negative with values ranging from -21.2 (April 2009) to -2.7 mmol m(-2) d(
      1) (January 2010). CH4 diffusive flux ranged from 0.1 (October 2009) to 0.6 mmol
      m(-2) d(-1) (April 2009) and no degassing downstream of the turbines was
      measured. As a consequence of these low values, the reservoir was a carbon sink
      with an estimated annual uptake of - 53+/-35 GgC yr(-1).

PMID- 21962560
TI  - Forecasting of daily air quality index in Delhi.
AB  - As the impact of air pollutants on human health through ambient air address much
      attention in recent years, the air quality forecasting in terms of air pollution
      parameters becomes an important topic in environmental science. The Air Quality
      Index (AQI) can be estimated through a formula, based on comprehensive assessment
      of concentration of air pollutants, which can be used by government agencies to
      characterize the status of air quality at a given location. The present study
      aims to develop forecasting model for predicting daily AQI, which can be used as
      a basis of decision making processes. Firstly, the AQI has been estimated through
      a method used by US Environmental Protection Agency (USEPA) for different
      criteria pollutants as Respirable Suspended Particulate Matter (RSPM), Sulfur
      dioxide (SO2), Nitrogen dioxide (NO2) and Suspended Particulate Matter (SPM).
      However, the sub-index and breakpoint concentrations in the formula are made
      according to Indian National Ambient Air Quality Standard. Secondly, the daily
      AQI for each season is forecasted through three statistical models namely time
      series auto regressive integrated moving average (ARIMA) (model 1), principal
      component regression (PCR) (model 2) and combination of both (model 3) in Delhi.
      The performance of all three models are evaluated with the help of observed
      concentrations of pollutants, which reflects that model 3 agrees well with
      observed values, as compared to the values of model 1 and model 2. The same is
      supported by the statistical parameters also. The significance of meteorological
      parameters of model 3 has been assessed through principal component analysis
      (PCA), which indicates that daily rainfall, station level pressure, daily mean
      temperature, wind direction index are maximum explained in summer, monsoon, post
      monsoon and winter respectively. Further, the variation of AQI during the
      weekends (holidays) and weekdays are found negligible. Therefore all the days of
      week are accounted same in the models.

PMID- 21962562
TI  - Cogs in the endless machine: lakes, climate change and nutrient cycles: a review.
AB  - Lakes have, rather grandly, been described as sentinels, integrators and
      regulators of climate change (Williamson et al., Limnol. Oceanogr. 2009; 54: 2273
      82). Lakes are also part of the continuum of the water cycle, cogs in a machine
      that processes water and elements dissolved and suspended in myriad forms.
      Assessing the changes in the functioning of the cogs and the machine with respect
      to these substances as climate changes is clearly important, but difficult. Many
      other human-induced influences, not least eutrophication, that impact on
      catchment areas and consequently on lakes, have generally complicated the
      recording of recent change in sediment records and modern sets of data. The least
      confounded evidence comes from remote lakes in mountain and polar regions and
      suggests effects of warming that include mobilisation of ions and increased
      amounts of phosphorus. A cottage industry has arisen in deduction and prediction
      of the future effects of climate change on lakes, but the results are very
      general and precision is marred not only by confounding influences but by the
      complexity of the lake system and the infinite variety of possible future
      scenarios. A common conclusion, however, is that warming will increase the
      intensity of symptoms of eutrophication. Direct experimentation, though expensive
      and still unusual and confined to shallow lake and wetland systems is perhaps the
      most reliable approach. Results suggest increased symptoms of eutrophication, and
      changes in ecosystem structure, but in some respects are different from those
      deduced from comparisons along latitudinal gradients or by inference from
      knowledge of lake behaviour. Experiments have shown marked increases in community
      respiration compared with gross photosynthesis in mesocosm systems and it may be
      that the most significant churnings of these cogs in the earth-air-water machine
      will be in their influence on the carbon cycle, with possibly large positive
      feedback effects on warming.

PMID- 21962563
TI  - Secular trends in fitness, moderate-to-vigorous physical activity, and TV-viewing
      among first grade school children of Crete, Greece between 1992/93 and 2006/07.
AB  - OBJECTIVES: To assess secular changes in physical fitness (PF), moderate-to
      vigorous-physical activity (MVPA) and TV-viewing in 1st-grade children from
      Crete, Greece. DESIGN: Cross-sectional cohorts examined in academic years 1992/93
      and 2006/07. METHODS: Two representative samples of children, aged 5.9-7.8 years,
      were studied during 1992/93 (N=606) and 2006/07 (N=361). PF (sit-and-reach,
      standing-broad-jump, sit-ups and 20 m-shuttle-run-test) was assessed by the
      European-PF test battery and MVPA by a physical activity (PA) questionnaire. Data
      on the frequency of TV-viewing was also collected. RESULTS: Between 1992/93 and
      2006/07, there was a significant increase in all fitness tests in both genders
      (P<0.001) and in MVPA in boys (76.5 min/week vs. 38.7 min/week, P<0.001). Time
      spent watching TV on weekdays was significantly more in both genders in 2006/07,
      compared to 1992/93 (P<0.001). In 2006/07, active boys and active girls spent
      more time in MVPA than active boys and girls in 1992/93 (P<0.001). Significantly
      higher proportions of boys and girls engaged in vigorous activities in 2006/07,
      than 1992/93 (P<0.001 and P=0.027, respectively). CONCLUSIONS: A significant
      increase in physical and cardiorespiratory fitness in both genders and MVPA in
      boys was observed in children from Crete between 1992/93 and 2006/07. The
      increase in weekday TV-viewing, despite being parallel to an increase in leisure
      time MVPA, could have an unfavorable effect on health and should be tackled in
      future interventions in this population. Dietary, anthropometric and biochemical
      indices should also be investigated to assess their impact on the secular changes
      in physical fitness and activity observed in this sample of children.

PMID- 21962564
TI  - Inflammatory markers and their relationships with leptin and insulin from acute
      mania to full remission in bipolar disorder.
AB  - BACKGROUND: Weight gain and increased production of leptin may be associated with
      immuno-modulation and insulin resistance in bipolar disorder. The links among
      inflammatory markers, leptin, and insulin of bipolar patients from acute mania to
      full remission remain unclear. METHODS: Thirty-three healthy, bipolar I patients
      under 45 years of age were enrolled. We measured the circulating levels of high
      sensitivity C-reactive protein (hs-CRP), anti-inflammatory mediators (interleukin
      1 receptor antagonist [IL-1Ra] and soluble tumor necrosis factor receptor 1 [sTNF
      R1]), leptin, and insulin during acute mania and subsequent partial and full
      remission. The results were compared with 33 age- and gender-matched healthy
      subjects. RESULTS: The levels of IL-1Ra and hs-CRP of bipolar patients in both
      acute mania and partial remission were significantly higher than their levels of
      control subjects. The hs-CRP level of bipolar patients was also elevated in full
      remission. The elevation of IL-1Ra and hs-CRP levels in acute mania was
      independent of each other. They were also independent of the body mass index
      (BMI) and levels of leptin and insulin measurements. The levels of leptin were
      all positively associated with insulin levels in the normal subjects and bipolar
      patients in three phases. However, a significant relationship between leptin and
      immunoparameter was only seen in full remission with sTNF-R1 (r=0.51).
      Furthermore, IL-1Ra was inversely correlated with sTNF-R1 (r=-0.37, p<0.05)
      during partly remission, and while levels of IL-1Ra tended to normalize when
      patients remitted, levels of hs-CRP and sTNF-R1 showed the opposite trend.
      CONCLUSIONS: Activated inflammation was found in acute mania, as evidenced by
      high levels of IL-1Ra, hs-CRP, and sTNF-R1. The production of leptin may be more
      tightly linked to insulin than the immunomodulators. Chronic inflammation may
      exist in bipolar patients and is reflected by elevations of IL-1Ra and hs-CRP
      levels in acute mania and persistent higher hs-CRP in full remission.

PMID- 21962565
TI  - Promoter variants in IL18 are associated with onset of depression in patients
      previously exposed to stressful-life events.
AB  - BACKGROUND: Depression is accompanied by an inflammatory reaction and activation
      of cell mediated immunity (CMI) and stressors may induce the cytokine network in
      humans. The proinflammatory cytokine interleukin-18 (IL-18) is less investigated
      in depression but highly relevant since it is produced by activated macrophages
      and expressed in the brain. METHODS: The distribution of six polymorphisms in
      IL10, IL18 and NF was compared between patients with a single episode of
      depression either preceded by a stressful life event (n=182), or occurring
      without a prior stressful life event (n=106) and a group of healthy control
      individuals (n=335). RESULTS: The major C allele of the IL18 rs187238 and the
      major G allele of rs1946518 had a significantly higher prevalence among the
      patients with a stressful life event prior to onset of disease than both patients
      without a stressful life event and compared with the healthy controls
      individuals. None of the examined IL10 or NF alleles were differently distributed
      among these groups. LIMITATIONS: Data are nominally significant and not resistant
      to correction for multiple testing. CONCLUSION: The major C allele of the IL18
      rs187238 and the major G allele rs1946518 have previously been associated with
      higher expression of IL-18 mRNA. Our data suggest that this genetic trend towards
      higher IL-18 production may increase the susceptibility to depression in response
      to stressful life events.

PMID- 21962566
TI  - Association between serotonin transporter gene promoter-region polymorphism and 4
      and 12-week treatment response to sertraline in posttraumatic stress disorder.
AB  - BACKGROUND: We examined the association between serotonin transporter (5HTTLPR)
      genotype (SS vs SL vs LL) and sertraline treatment outcome in posttraumatic
      stress disorder (PTSD). METHODS: Outpatients (n=330) with PTSD underwent 5HTTLPR
      genotyping. All patients received sertraline (100 mg/day) for 12 weeks. Patients
      were assessed using the Clinician-Administered PTSD Scale (CAPS) and other
      instruments. Patients and rater were blind to the genotyping results. The primary
      outcome was completer sample CAPS improvement at 12 weeks. Response was defined
      as >=30% improvement in CAPS total score with a CGI-I score of 1 or 2. RESULTS:
      The discontinuation rate was 31.5%. Adverse events led to drop out in 18.1%,
      15.3%, and 5.9% of SS, SL, and LL patients, respectively (P=0.038). Among
      completers, there were 95, 43, and 88 patients with the SS, SL, and LL genotypes,
      respectively. At endpoint, CAPS total scores improved by 26% vs 46%,
      respectively, in SS and SL vs LL patients (P<0.001); much of this improvement
      (15% vs 31% in SS and SL vs LL patients, respectively; P<0.001) was apparent by
      week 4. The findings were largely similar for the other outcome measures. The
      response rate was 0%, 0%, and 47.7% in the SS, SL, and LL groups, respectively
      (P<0.001). LIMITATIONS: We administered a fixed dose of sertraline. For
      sociopolitical reasons, we planned a completer analysis only. CONCLUSIONS:
      Relative to the SS and SL 5HTTLPR genotypes, the LL genotype is associated with
      greater responsiveness of PTSD to sertraline (100mg/day) and with lower drop out
      due to adverse events. The S allele is associated with a striking specificity for
      treatment nonresponse, as defined in this study.

PMID- 21962567
TI  - The matricellular protein SPARC supports follicular dendritic cell networking
      toward Th17 responses.
AB  - Lymphnode swelling during immune responses is a transient, finely regulated
      tissue rearrangement, accomplished with the participation of the extracellular
      matrix. Here we show that murine and human reactive lymph nodes express SPARC in
      the germinal centres. Defective follicular dendritic cell networking in SPARC
      deficient mice is accompanied by a severe delay in the arrangement of germinal
      centres and development of humoral autoimmunity, events that are linked to Th17
      development. SPARC is required for the optimal and rapid differentiation of Th17
      cells, accordingly we show delayed development of experimental autoimmune
      encephalomyelitis whose pathogenesis involves Th17. Not only host radioresistant
      cells, namely follicular dendritic cells, but also CD4(+) cells are the relevant
      sources of SPARC, in vivo. Th17 differentiation and germinal centre formation
      mutually depend on SPARC for a proper functional crosstalk. Indeed, Th17 cells
      can enter the germinal centres in SPARC-competent, but not SPARC-deficient, mice.
      In summary, SPARC optimizes the changes occurring in lymphoid extracellular
      matrix harboring complex interactions between follicular dendritic cells, B cells
      and Th17 cells.

PMID- 21962568
TI  - Impact of mercury exposure on blood pressure and cardiac autonomic activity among
      Cree adults (James Bay, Quebec, Canada).
AB  - Aboriginal populations from Quebec (Canada) are exposed to higher mercury levels
      than southern regions since these populations consume high quantities of fish.
      Epidemiological evidence suggests a detrimental impact of mercury on
      cardiovascular risk factors such as heart rate variability (HRV) and blood
      pressure (BP). The objective of this study was to assess the impact of mercury
      exposure on BP, resting heart rate (HR) and HRV among Cree adults. Data were
      collected among 791 adults>=18 years old living in seven communities of the James
      Bay. Blood mercury and hair levels were used as biomarkers of recent and long
      term exposure. BP was measured through a standardised protocol while HRV was
      derived from a 2-h Holter monitoring assessment. The relationship between mercury
      and the outcomes was studied using ANOVA and ANCOVA analysis. Geometric mean of
      blood mercury and hair mercury concentration was 17.0 nmol/L (95%CI: 6.1-44.0)
      and 2.36 nmol/g (95%CI: 2.09-2.65); respectively. After adjusting for
      confounders, blood mercury was associated with HRV parameters such as LF
      (beta=0.21, P=0.0002), HF (beta=0.15, P=0.004) and LF/HF (beta=0.06, P=0.003).
      Similar associations were observed with hair mercury. In contrast, no significant
      association was observed between blood mercury or hair mercury and BP after
      adjusting for confounders. In conclusion, mercury exposure seems to affect HRV
      among Cree adults even after considering fish nutrients (n-3 fatty acids and
      selenium) and other contaminants (lead and polychlorinated biphenyls) that are
      also present in the traditional diet of this population.

PMID- 21962569
TI  - Assessment of vaccine testing at three laboratories using the guinea pig model of
      tuberculosis.
AB  - The guinea pig model of tuberculosis is used extensively in different locations
      to assess the efficacy of novel tuberculosis vaccines during pre-clinical
      development. Two key assays are used to measure protection against virulent
      challenge: a 30 day post-infection assessment of mycobacterial burden and long
      term post-infection survival and pathology analysis. To determine the consistency
      and robustness of the guinea pig model for testing vaccines, a comparative
      assessment between three sites that are currently involved in testing
      tuberculosis vaccines from external providers was performed. Each site was asked
      to test two "subunit" type vaccines in their routine animal model as if testing
      vaccines from a provider. All sites performed a 30 day study, and one site also
      performed a long-term survival/pathology study. Despite some differences in
      experimental approach between the sites, such as the origin of the Mycobacterium
      tuberculosis strain and the type of aerosol exposure device used to infect the
      animals and the source of the guinea pigs, the data obtained between sites were
      consistent in regard to the ability of each "vaccine" tested to reduce the
      mycobacterial burden. The observations also showed that there was good
      concurrence between the results of short-term and long-term studies. This
      validation exercise means that efficacy data can be compared between sites.

PMID- 21962570
TI  - A new method for long-term home monitoring of fetal movement by pregnant women
      themselves.
AB  - Fetal movement is one index of fetal well-being. We designed and built a new
      recorder based on fetal movement acceleration measurement (FMAM). The FMAM
      recorder has a newly developed, capacitive acceleration sensor that can detect
      the oscillations of the maternal abdominal wall caused by fetal movements. In
      this study, the recorder was examined for its suitability for long-term home
      monitoring of fetal movement by pregnant women themselves. Experiment I: Fourteen
      pregnant women underwent 45 examinations in the laboratory at gestational 20-39
      weeks. We simultaneously recorded fetal movement as detected by the recorder,
      ultrasonography, and maternal perception, and then calculated agreement among the
      three methods. We evaluated agreement using prevalence-adjusted bias-adjusted
      kappa (PABAK). Agreement for gross fetal movement as detected by FMAM and
      ultrasonography was substantial or almost perfect, while agreement between
      maternal perception and ultrasonography was moderate or substantial. Experiment
      II: Six pregnant women undertook 53 experiments at home by themselves. Fetal
      movement during maternal nocturnal sleep was successfully recorded 50 out of 53
      times at home. In conclusion, there was high agreement for gross fetal movement
      between FMAM and ultrasonography. The recorder is promising for objective,
      accurate, and long-term home monitoring of gross fetal movement by pregnant women
      themselves.

PMID- 21962571
TI  - Interleukin-17A is involved in enhancement of tumor progression in murine
      intestine.
AB  - Interleukin (IL)-17A is a cytokine involved in neutrophilic inflammation but the
      role of IL-17A in anti-tumor immunity is controversial because both pro- and anti
      tumor activities of IL-17A have been reported. We hypothesized that constitutive
      expression of IL-17A in intestinal environment modifies tumor growth. To address
      the issue, mice were inoculated into subserosa of cecum (i.c.) with murine EL4
      lymphoma expressing a model tumor antigen, and tumor growth was monitored. IL-17A
      producing cells were detected both in tumor mass and in normal intestinal tissue
      of i.c. tumor-bearing wild type mice. Tumor size in the wild-type mice was
      significantly higher than that in the cecum of IL-17A gene-knockout mice.
      Furthermore, anti-IL-17A monoclonal antibody treatment of wild-type mice resulted
      in decreased tumor size in the cecum. Model tumor-antigen-specific interferon
      gamma production was not modified in draining mesenteric lymph node cells in the
      absence or after neutralization of IL-17A. All the results suggest that
      constitutive expression of IL-17A in intestine enhances tumor growth, and anti-IL
      17A antibody treatment is a candidate of a new anti-tumor immunotherapy against
      intestinal tumors.

PMID- 21962572
TI  - Association of HLA class II alleles with sensitization to cow dander Bos d 2, an
      important occupational allergen.
AB  - Allergic sensitization results from a complex interaction between genetic and
      environmental factors. Earlier studies have shown that highly polymorphic HLA
      genes are associated with a variety of allergies. Several important respiratory
      allergens belong to the family of lipocalin proteins. These include occupational
      sensitizers, such as cow Bos d 2 or rat Rat n 1, and prevalent indoor
      sensitizers, such as dog Can f 1 or cockroach Bla g 4. HLA associations with
      sensitization to lipocalin allergens are incompletely known. In the present study
      we have investigated an association between HLA alleles and sensitization to the
      major cow allergen Bos d 2. The HLA-DR/DQ genotypes of 40 Bos d 2-sensitized
      subjects having occupational asthma were determined by polymerase chain reaction
      (PCR) and the results were compared with the genotypes of 151 unrelated Finnish
      subjects. The frequencies of HLA class II alleles DRB1*0101, DRB1*0404,
      DQB1*0302, and DQB1*0501 were significantly higher among Bos d 2-sensitized than
      among control subjects. In addition, the allergic subjects expressed
      significantly lower frequencies of HLA-DRB1*0301 and DQB1*0201 alleles than did
      the control subjects. These data suggest that the HLA class II alleles DRB1*0101,
      DRB1*0404, DQB1*0302, and DQB1*0501, and the haplotypes that include them, are
      associated with sensitization to the major cow allergen Bos d 2, whereas HLA
      DRB1*0301 and DQB1*0201 are dissociated with it. Amino acid analysis provides a
      biologically plausible explanation for the HLA associations.

PMID- 21962573
TI  - Molecular immune recognition of botulinum neurotoxin B. The light chain regions
      that bind human blocking antibodies from toxin-treated cervical dystonia
      patients. Antigenic structure of the entire BoNT/B molecule.
AB  - We recently mapped the regions on the heavy (H) chain of botulinum neurotoxin,
      type B (BoNT/B) recognized by blocking antibodies (Abs) from cervical dystonia
      (CD) patients who develop immunoresistance during toxin treatment. Since blocking
      could also be effected by Abs directed against regions on the light (L) chain, we
      have mapped here the L chain, using the same 30 CD antisera. We synthesized,
      purified and characterized 32 19-residue L chain peptides that overlapped
      successively by 5 residues (peptide L32 overlapped with peptide N1 of the H chain
      by 12 residues). In a given patient, Abs against the L chain seemed less intense
      than those against H chain. Most sera recognized a limited set of L chain
      peptides. The levels of Abs against a given region varied with the patient,
      consistent with immune responses to each epitope being under separate MHC
      control. The peptides most frequently recognized were: L13, by 30 of 30 antisera
      (100%); L22, by 23 of 30 (76.67%); L19, by 15 of 30 (50.00%); L26, by 11 of 30
      (36.70%); and L14, by 12 of 30 (40.00%). The activity of L14 probably derives
      from its overlap with L13. The levels of Ab binding decreased in the following
      order: L13 (residues 169-187), L22 (295-313), L19 (253-271), and L26 (351-369).
      Peptides L12 (155-173), L18 (239-257), L15 (197-215), L1 (1-19) and L23 (309-327)
      exhibited very low Ab binding. The remaining peptides had little or no Ab-binding
      activity. The antigenic regions are analyzed in terms of their three-dimensional
      locations and the enzyme active site. With the previous localization of the
      antigenic regions on the BoNT/B H chain, the human Ab recognition of the entire
      BoNT/B molecule is presented and compared to the recognition of BoNT/A by human
      blocking Abs.

PMID- 21962574
TI  - Localization factor: a new parameter for the quantitative characterization of
      surface structure with atomic force microscopy (AFM).
AB  - In this work we present the possible application of a new parameter called
      localization factor for the quantitative characterization of surface structures
      with atomic force microscopy (AFM). For this purpose contact mode AFM images were
      taken from technologically different polycrystalline gold thin films and were
      evaluated according to the following parameters: surface roughness (R(a),
      R(RMS)), roughness factor (f(r)) and localization factor. The localization factor
      was compared with the other surface parameters. We demonstrate that this new
      parameter can be used to identically characterize these gold thin film surfaces
      with contact mode AFM in the 1-1000 MUm(2) scan range. The mathematical
      background and possible application fields of the localization factor are also
      discussed in our paper.

PMID- 21962575
TI  - Characterization of a novel and selective CB1 antagonist as a radioligand for
      receptor occupancy studies.
AB  - Obesity remains a significant public health issue leading to Type II diabetes and
      cardiovascular disease. CB1 antagonists have been shown to suppress appetite and
      reduce body weight in animal models as well as in humans. Evaluation of pre
      clinical CB1 antagonists to establish relationships between in vitro affinity and
      in vivo efficacy parameters are enhanced by ex vivo receptor occupancy data.
      Synthesis and biological evaluation of a novel and highly selective radiolabeled
      CB1 antagonist is described. The radioligand was used to conduct ex vivo receptor
      occupancy studies.

PMID- 21962576
TI  - Computational techniques are valuable tools for the discovery of protein-protein
      interaction inhibitors: the 14-3-3sigma case.
AB  - Targeting the binding site of 14-3-3 proteins lets the release of partner
      proteins involved in cell cycle progression, apoptosis, cytoskeletal
      rearrangement and transcriptional regulation and may therefore be regarded as an
      alternative strategy to integrate conventional therapeutic approaches against
      cancer. In the present work, we report the identification of two new small
      molecule inhibitors of 14-3-3sigma/c-Abl protein-protein interaction (BV01 and
      BV101) discovered by means of computational methods. The most interesting
      compound (BV01) showed a lethal dose (LD(50)) in the low micromolar range against
      Ba/F3 murine cell lines expressing the Imatinib (IM)-sensitive wild type Bcr-Abl
      construct and the IM-resistant Bcr-Abl mutation T315I. BV01 interaction with 14-3
      3sigma was demonstrated by NMR studies and elucidated by docking. It blocked the
      binding domain of 14-3-3sigma, hence promoting the release of the partner protein
      c-Abl (the one not involved in Bcr rearrangement), and its translocation to both
      the nuclear compartment and mitochondrial membranes to induce a pro-apoptotic
      response. Our results advance BV01 as a confirmed hit compound capable of
      eliciting apoptotic death of Bcr-Abl-expressing cells by interfering with 14-3
      3sigma/c-Abl protein-protein interaction.

PMID- 21962577
TI  - Fatty acids as natural specific inhibitors of the proto-oncogenic protein Shp2.
AB  - Src homology-2 domain-containing protein tyrosine phosphatase (Shp2), a novel
      proto-oncogenic protein, is an important target in cancer therapy research.
      Approximately 2000 plant extracts were screened to find its natural specific
      inhibitors, with the ethyl acetate (EtOAc) active extract of the root of Angelica
      dahurica showing considerable inhibitory effects (IC(50)=21.6 mg/L). Bioguided
      isolation of EtOAc extract led to 13 compounds, including 10 fatty acids and
      derivatives. All these compounds were isolated from the plant for the first time.
      The inhibitory effects of these compounds on the enzyme activities of Shp2, VH1
      related human protein (VHR), and hematopoietic protein tyrosine phosphatase
      (HePTP) were investigated. 8Z,11Z-Feptadecadienoic acid (4), 14Z,17Z
      tricosadienoic acid (5), caffeic acid (9), and 2-hydroxy-3-[(1-oxododecyl)
      oxy]propyl-beta-d-glucopyranoside (11) showed considerable selective inhibition
      of Shp2 activity. After treatment of HepG2 cells with the compounds, only
      compound 5, a polyunsaturated fatty acid, strongly induced poly (ADP-ribose)
      polymerase (PARP) cleavage in a dose- and time-dependent manner and increased the
      activities of caspase-3, caspase-8, and caspase-9 at 100 MUM. Compound 5 also
      inhibited colony formation of HepG2 cells in a dose-dependent manner. Thus, this
      study reported fatty acids as specific Shp2 inhibitors and provided the molecular
      basis of one active compound as novel potential anticancer drug.

PMID- 21962578
TI  - Synthesis and in vivo evaluation of [18F]N-(2-benzofuranylmethyl)-N'-[4-(2
      fluoroethoxy)benzyl]piperazine, a novel sigma1 receptor PET imaging agent.
AB  - N-(2-Benzofuranylmethyl)-N'-[4-(2-fluoroethoxy)benzyl]piperazine (6,
      sigma(1)K(i)=2.6 nM) was radiolabeled with fluorine-18 to provide a potential
      sigma(1) receptor radioligand for use in positron emission tomography (PET).
      Radiofluorination of the appropriate tosylate precursor furnished [(18)F]6 with a
      specific activity of 45 GBq/MUmol, in an average radiochemical yield of 18% and
      greater than 98% radiochemical purity. MicroPET imaging in Papio hamadryas baboon
      brain revealed [(18)F]6 uptake consistent with sigma receptor distribution, and
      specificity for sigma receptors was demonstrated in a haloperidol pre-treated
      animal. [(18)F]6 possesses suitable properties for PET imaging of sigma(1)
      receptors, and further investigation of this sigma(1) receptor tracer is
      warranted.

PMID- 21962579
TI  - Estimating axial and lateral strain using a synthetic aperture elastographic
      imaging system.
AB  - Model-based elastography is an emerging technique with clinical applications in
      imaging vascular tissues, guiding minimally invasive therapies and diagnosing
      breast and prostate cancers. Its usage is limited because ultrasound can measure
      only the axial component of displacement with high precision. The goal of this
      study was to assess the effect of lateral sampling frequency, lateral beam-width
      and the number of active transmission elements on the quality of axial and
      lateral strain elastograms. Elastographic imaging was performed on gelatin-based
      phantoms with a modified commercial ultrasound scanner. Three groups of radio
      frequency (RF) echo frames were reconstructed from fully synthetic aperture data.
      In the first group, all 128 transmission elements (corresponding to a lateral
      beamwidth of 0.22 mm at the center of the field of view) were used to reconstruct
      RF echo frames with A-line densities that varied from 6.4 lines/mm to 51.2
      lines/mm. In the second group, the size of the aperture was varied to produce RF
      echo frames with lateral beamwidths ranging from 0.22 mm to 0.43 mm and a fixed A
      line density of 25.6 lines/mm. In the third group, sparse arrays with varying
      number of active transmission elements (from 2 to 128) were used to reconstruct
      RF echo frames, whose A-line density and lateral beamwidth were fixed to 25.6
      lines/mm and 0.22 mm, respectively. Applying a two-dimensional (2-D) displacement
      estimator to the pre- and post-deformed RF echo frames produced displacement
      elastograms. Axial and lateral strain elastograms were computed from displacement
      elastograms with a least squares strain estimator. The quality of axial and
      lateral strain elastograms improved with increasing applied strain and A-line
      density but decreased with increasing lateral beamwidth and deteriorated as the
      number of active transmission elements in the sparse arrays were reduced. This
      work demonstrated that the variance incurred when estimating the lateral
      component of displacement was reduced considerably when elastography was
      performed with a synthetic aperture ultrasound imaging system. Satisfactory axial
      and lateral strain elastograms were produced using a sparse array with as few as
      16 active transmission elements.

PMID- 21962580
TI  - Innate immune cells in motion.

PMID- 21962581
TI  - Management of misangulated implants for a maxillary overdenture with spherical
      abutments: a clinical report.
AB  - Misangulated and malpositioned implants pose a significant challenge for the
      prosthodontic treatment of edentulous patients. Most reports of maxillary
      overdenture patients have described the use of a bar to splint malaligned
      implants, followed by successful fabrication of the prosthesis. Few reports have
      discussed the use of individual abutments in such situations. This clinical
      report describes the successful use of spherical/ball abutments for the
      management of 4 malaligned implants in the edentulous maxilla for an overdenture.
      The rationale and technique for the use of spherical abutments for overdenture
      fabrication in such situations are described.

PMID- 21962582
TI  - Nonrigid connection of tooth with implants in the esthetic zone with a ceramic
      restoration: a clinical report.
AB  - Restoring edentulous areas with fixed prostheses can be challenging, especially
      when key abutment teeth are missing and implant placement is not an option.
      Sometimes, clinicians are faced with situations where teeth have to be connected
      with implants even though long-term prognosis of those connections may be
      questionable. This clinical report presents a connection of 2 implants with 1
      tooth in the esthetic zone with a nonrigid connection. Two zirconia custom
      abutments and 1 zirconia coping definitively cemented on the tooth were used. A
      zirconia superstructure, veneered with porcelain, was cemented with provisional
      cement on the abutments and the coping.

PMID- 21962583
TI  - Severe and rapid erosion of dental enamel from swimming: a clinical report.
AB  - The diagnosis and treatment of a patient with excessive and rapid erosion of
      enamel is presented. Although the Center for Disease Control and the dental
      literature have reported on dental enamel erosion resulting from swimming pool
      chlorination, the awareness of such etiology among dental professionals may be
      limited. Common findings in these reports include cold sensitivity, a distinctive
      appearance resembling laminate veneer preparations of the facial surfaces of
      anterior teeth, occurrence of diastemas, and at times, a rough or gritty texture
      of the remaining tooth structure. Clinical presentations of erosive lesions can
      be diagnosed and the best course of treatment determined.

PMID- 21962584
TI  - Annual review of selected scientific literature: report of the committee on
      scientific investigation of the American Academy of Restorative Dentistry.

PMID- 21962585
TI  - Photoelastic stress analysis of external versus internal implant-abutment
      connections.
AB  - STATEMENT OF PROBLEM: Common complications of implant restorations are abutment
      screw loosening and screw fracture. The geometry of the implant-abutment
      connection may affect stresses generated from loading, and these stresses may
      have a role in screw loosening or fracture. PURPOSE: This study compared the load
      transfer characteristics of a complete-arch restoration supported by 4 implants
      with external and internal implant-abutment connections. Loads were applied to
      the prostheses in 3 positions. MATERIAL AND METHODS: Two-dimensional photoelastic
      models were used to simulate bone. Two types of implants (ReplaceSelect Internal
      Interface Tapered Implants and ReplaceSelect External-Interface Tapered Implants)
      were placed in the photoelastic models. Complete-arch metal frameworks were
      fabricated on the abutments. Artificial teeth were arranged on the framework, and
      the prosthesis was screwed onto the abutments. The specimens were analyzed at 2
      levels (implant-abutment level and apical to the implant level) with 3 loading
      conditions (4-point load; 2-point anterior load; and 2-point lateral load). The
      numbers of fringe orders were recorded and compared. RESULTS: With the 4-point
      load, no stress differences occurred between the external-implant abutment
      connection and internal-implant abutment connection at the connection level and
      at the apical level. With the 2-point anterior load, the internal-implant
      abutment connection resulted in lower stresses at the connection level both in
      the loaded and non-loaded areas. With the 2-point lateral load, the internal
      implant abutment connection resulted in lower stresses at the connection level at
      the non-loaded area. CONCLUSIONS: When loaded off-center, the internal-implant
      abutment connection produced less stress when compared with the external-implant
      abutment connection.

PMID- 21962586
TI  - A segmented implant surgical guide connected with magnets.
AB  - The 2-piece surgical guide introduced in this article is designed for guiding
      implant placement in the edentulous arch. With the aid of embedded magnets, this
      guide can be easily and quickly assembled and disassembled during the surgical
      procedure without losing the predetermined guidance for the implant placement.

PMID- 21962587
TI  - The burden of postoperative delirium after vascular surgery.

PMID- 21962588
TI  - Single-centre prospective comparison between contrast-enhanced ultrasound and
      computed tomography angiography after EVAR.
AB  - AIM: To evaluate contrast-enhanced ultrasound (CEUS) as an effective alternative
      to CT-angiography (CTA) for endoleak detection and aneurismal sac diameter
      measurement in the follow-up after endovascular abdominal aortic aneurysm repair
      (EVAR). METHODS: From January 2006 to December 2010, 395 patients underwent EVAR
      follow-up with both CTA and CEUS. The diameter of the aneurismal sac and the
      presence of endoleaks were evaluated in all the 395 paired examinations. RESULTS:
      Bland-Altman plots showed a good agreement in aneurismal sac diameter evaluation
      between the two imaging modalities. The mean diameter was 54.93 mm (standard
      deviation (SD) +/-12.57) with CEUS and 56.01 mm (SD +/- 13.23) with CTA. The mean
      difference in aneurismal sac diameter was -1.08 mm +/- 3.3543 (95% confidence
      interval (CI), -0.75 to -1.41), in favour of CTA. The number of observed
      agreement in endoleak detection was 359/395 (90.89%). The two modalities detected
      the same type I and type III endoleaks. McNemar's chi(2) test confirmed that CTA
      and CEUS are equivalent in endoleak detection. CONCLUSIONS: CEUS demonstrated to
      be as accurate as CTA in endoleak detection and abdominal aortic aneurysm
      diameter measurements during EVAR follow-up, without carrying the risks of
      radiation exposure or nephrotoxicity. Even if it cannot be proposed as the sole
      imaging modality during follow-up, our analysis suggests that it should have a
      major role.

PMID- 21962589
TI  - CCSVI and MS: a never-ending story.

PMID- 21962590
TI  - Occurrence of oligosaccharides in feces of breast-fed babies in their first six
      months of life and the corresponding breast milk.
AB  - The characterization of oligosaccharides in the feces of breast-fed babies is a
      valuable tool for monitoring the gastrointestinal fate of human milk
      oligosaccharides (HMOs). In the present study we monitored fecal oligosaccharide
      profiles together with the HMO-profiles of the respective breast milks up to six
      months postpartum, by means of capillary electrophoresis-laser induced
      fluorescence detection and mass spectrometry. Eleven mother/child pairs were
      included. Mother's secretor- and Lewis-type included all combinations [Le(a-b+),
      Le(a+b-), Le(a-b-)]. The fecal HMO-profiles in the first few months of life are
      either predominantly composed of neutral or acidic HMOs and are possibly effected
      by the HMO-fingerprint in the respective breast milk. Independent of the initial
      presence of acidic or neutral fecal HMOs, a gradual change to blood-group
      specific oligosaccharides was observed. Their presence pointed to a
      gastrointestinal degradation of the feeding-related HMOs, followed by conjugation
      with blood group specific antigenic determinants present in the gastrointestinal
      mucus layer. Eleven of these 'hybrid'-oligosaccharides were annotated in this
      study. When solid food was introduced, no HMOs and their degradation- and
      metabolization products were recovered in the fecal samples.

PMID- 21962592
TI  - Effect of air and noise pollution on species diversity and population density of
      forest birds at Lalpahari, West Bengal, India.
AB  - The Rajmahal-type quality stones for building purposes are found abundantly in
      Birbhum district, West Bengal, India, where stone mining and crushing have become
      the main industrial activity. Although crusher dust is injurious to health,
      demand for crushed stone is ever-increasing as a result of rapid infrastructural
      growth in the country. Most of the crusher units at Rampurhat are situated along
      the roadways adjacent to forest under Tumboni Beat of Rampurhat Range of Birbhum
      Forest Division. Excessive load of air pollution in this area has led to
      degradation of this forest. The status of the ambient air and noise level was
      evaluated. The effect of air and noise pollution on abundance and variability of
      birds in this forest have been compared to an almost non-polluted forest of the
      same bio-geographic zone. Both species diversity and population density of birds
      were found to decrease in the polluted forest, especially in the areas adjacent
      to crushers. For comparing the pollution status of two different forest sites and
      for establishing whether the density of birds have any correlation between the
      sites, the Student's t-test and the chi-square test were applied respectively.
      Most of the results proved to be significant.

PMID- 21962591
TI  - Development of chitosan-tripolyphosphate fibers through pH dependent ionotropic
      gelation.
AB  - Incorporation of phosphate groups into a material may be of particular interest
      as they act as templates for hydroxyapatite growth through complexation with
      Ca(2+) and thus improve the osteoconduction property. The phosphate groups can be
      incorporated into chitosan through ionotropic gelation with tripolyphosphate
      (TPP). Interestingly, the ion pairs formed through negatively charged phosphate
      groups with protonated amine functionality of chitosan in ionotropic gelation are
      expected to provide chitosan with an amphoteric character, which may facilitate
      protein adhesion following enhanced attachment of anchorage dependant cells than
      chitosan, which shows poor cell adhesion properties. In this study, chitosan
      tripolyphosphate (TPP) fibers with varying phosphate contents were prepared
      through wet spinning in STPP baths of different pH. Gelation kinetics and gel
      strength of chitosan with STPP solutions of three different pH were evaluated and
      compared with that of NaOH solution for evaluation of their influence on nature
      of gelation. The solution pH of STPP baths was found to have significant control
      on the extent of ionic cross-linking and physico-chemical properties of the
      fibers. Moreover, this kinetically driven ionotropic gelation of chitosan by TPP
      results in low degree of crystallinity of chitosan-TPP fibers and consequently
      their lower thermal stability than chitosan fibers.

PMID- 21962593
TI  - Effect of prenatal exposure to fine particulate matter and intake of Paracetamol
      (Acetaminophen) in pregnancy on eczema occurrence in early childhood.
AB  - The goal of the study was to test the hypothesis that prenatal Paracetamol
      exposure increases the risk of developing eczema in early childhood and that this
      association may be stronger in children who are exposed in fetal period to higher
      concentrations of fine particulate matter (PM2.5). The study sample consisted of
      322 women recruited from January 2001 to February 2004 in the Krakow inner city
      area who gave birth to term babies and completed 5-year follow-up. Paracetamol
      use in pregnancy was collected by interviews and prenatal personal exposure to
      PM2.5 over 48 h was measured in recruited women in the second trimester of
      pregnancy. After delivery, every three months in the first 24 months of the
      newborn's life and every 6 months later, a detailed standardized face-to-face
      interview on the infant's health was administered to each mother by trained
      interviewers. During the interviews at each of the study periods after birth, a
      history of eczema was recorded. The incident rate ratio (IRR) for frequency of
      eczema events over the follow-up was estimated from the Poisson regression model
      and the overall effect of main exposure variables on eczema was assessed by odds
      ratios (ORs) by the logistic model. The estimated relative risk of eczema
      occurring whenever in the follow-up was related significantly neither with
      prenatal Paracetamol nor higher PM2.5 exposure, however, their joint effect was
      significant (OR interaction term=6.04; 95%CI: 1.04-35.16). Of potential
      confounders considered in the analysis only damp/moldy home significantly
      increased the risk of eczema (OR=1.53; 95%CI: 1.14-2.05). In contrast, there was
      an inverse significant association between the presence of older siblings and
      eczema (OR=0.55; 95%CI: 0.35-0.84). The joint effect of the main exposure
      variables significantly increased frequency of eczema events (IRR=1.78, 95%CI:
      1.22-2.61). In conclusion, the findings of the study suggest that Paracetamol use
      by mothers in pregnancy is not an independent risk factor for eczema in children,
      however, even very small doses of Paracetamol taken in pregnancy may contribute
      to the occurrence of allergic symptoms in early childhood if there is prenatal co
      exposure to higher airborne fine particulate matter.

PMID- 21962594
TI  - Sources of variation in the assimilation of lead by a common gastropod sentinel
      Cantareus aspersus.
AB  - The assimilation efficiency of Pb was measured in the candidate sentinel
      Cantareus aspersus, to assess its capacity to consistently represent the
      bioavailability of Pb. Three populations were compared from habitats with
      different levels of toxic and essential metals. For each, 36 snails were fed a
      laboratory diet with known concentrations of Pb, Ca and Mg over 64 days. Lead
      bioavailability was measured as the percentage assimilation by the soft tissues
      (mass in tissues as a fraction of that consumed), and its variation was assessed
      between populations, exposure periods, dietary Mg and replicates. The indicated
      bioavailability was consistent over time and Pb consumed, but differed between
      populations and diets. Population differences were due, in part, to their
      different growth rates: soft tissue growth was positively correlated with Pb mass
      and, in the most rapidly growing populations, this accounted for more than 40% of
      the variation in soft tissue Pb. Populations did not differ in their consumption
      of Pb, but the highest Mg diet induced higher food consumption and a reduced
      assimilation of Pb. Tissue growth determines retention and contributes to the
      variation in the bioavailability indicated by these populations, as do essential
      metals in the diet. Such variability has important implications for monitoring
      programmes using resident populations of sentinels to map the bioavailability of
      toxic metals or integrate a pollution signal over time.

PMID- 21962595
TI  - Archaeological recording and chemical stratigraphy applied to contaminated land
      studies.
AB  - The method used by archaeologists for excavation and recording of the
      stratigraphic evidence, within trenches with or without archaeological remains,
      can potentially be useful to contaminated land consultants (CLCs). The
      implementation of archaeological practice in contaminated land assessments (CLAs)
      is not meant to be an exercise in data overkill; neither should it increase
      costs. Rather, we suggest, that if the excavation and recording, by a trained
      archaeologist, of the stratigraphy is followed by in-situ chemical
      characterisation then it is possible that much uncertainty associated with
      current field sampling practices, may be removed. This is because built into the
      chemical stratigraphy is the temporal and spatial relationship between different
      parts of the site reflecting the logic behind the distribution of contamination.
      An archaeological recording with chemical stratigraphy approach to sampling may
      possibly provide 'one method fits all' for potentially contaminated land sites
      (CLSs), just as archaeological characterisation of the stratigraphic record
      provides 'one method fits all' for all archaeological sites irrespective of
      period (prehistoric to modern) or type (rural, urban or industrial). We also
      suggest that there may be practical and financial benefits to be gained by
      pulling together expertise and resources stemming from different disciplines, not
      simply at the assessment phase, but also subsequent phases, in contaminated land
      improvement.

PMID- 21962596
TI  - Development of a dynamic model for estimating the food web transfer of chemicals
      in small aquatic ecosystems.
AB  - A dynamic combined fate and food web model was developed to estimate the food web
      transfer of chemicals in small aquatic ecosystems (i.e. ponds). A novel feature
      of the modeling approach is that aquatic macrophytes (submerged aquatic
      vegetation) were included in the fate model and were also a food item in the food
      web model. The paper aims to investigate whether macrophytes are effective at
      mitigating chemical exposure and to compare the modeling approach developed here
      with previous modeling approaches recommended in the European Union (EU)
      guideline for risk assessment of pesticides. The model was used to estimate
      bioaccumulation of three hypothetical chemicals of varying hydrophobicity in a
      pond food web comprising 11 species. Three different macrophyte biomass densities
      were simulated in the model experiments to determine the influence of macrophytes
      on fate and bioaccumulation. Macrophytes were shown to have a significant effect
      on the fate and food web transfer of highly hydrophobic compounds with log
      KOW>=5. Modeled peak concentrations in biota were highest for the scenarios with
      the lowest macrophyte biomass density. The distribution and food web transfer of
      the hypothetical compound with the lowest hydrophobicity (log KOW=3) was not
      affected by the inclusion of aquatic macrophytes in the pond environment. For the
      three different hypothetical chemicals and at all macrophyte biomass densities,
      the maximum predicted concentrations in the top predator in the food web model
      were at least one order of magnitude lower than the values estimated using
      methods suggested in EU guidelines. The EU guideline thus provides a highly
      conservative estimate of risk. In our opinion, and subject to further model
      evaluation, a realistic assessment of dynamic food web transfer and risk can be
      obtained using the model presented here.

PMID- 21962597
TI  - Altered developmental timing in early life stages of Antarctic krill (Euphausia
      superba) exposed to p,p'-DDE.
AB  - Persistent organic pollutants (POPs) are persistent, toxic and bioaccumulative
      anthropogenic organic chemicals, capable of undergoing long range environmental
      transport to remote areas including the Antarctic. p,p'-dichlorodiphenyl
      dichloroethylene (p,p'-DDE) has been identified as a dominant POP accumulating in
      Antarctic krill (Euphausia superba), which is a key Southern Ocean species. This
      study examined the developmental toxicity of p,p'-DDE via aqueous exposure to
      Antarctic krill larvae. p,p'-DDE exposure was found to stimulate developmental
      timing in the first three larval stages of Antarctic krill, while extended
      monitoring of larvae after a five day exposure period had ended, revealed delayed
      inhibitory responses during development to the fourth larval stage. Stimulatory
      responses were observed from the lowest p,p'-DDE body residue tested of 10.1+/
      3.0 MUmol/kg (3.2+/-0.95 mg/kg) preserved wet weight, which is comparable to
      findings for temperate species and an order of magnitude lower than the exposure
      level found to cause sublethal behavioural effects in Antarctic krill. The
      delayed responses included increased mortality, which had doubled in the highest
      p,p'-DDE treatment (95+/-8.9% mortality at 20 MUg/L p,p'-DDE) compared to the
      solvent control (44+/-11% mortality) 2 weeks after end of exposure. Development
      of surviving metanauplius larvae to calyptopis 1 larvae was delayed by 2 days in
      p,p'-DDE exposed larvae compared with untreated larvae. Finally, the
      developmental success of surviving p,p'-DDE exposed larvae was reduced by 50 to
      75% compared to the solvent control (100% developmental success). The lowest
      observed effect concentration for all delayed effects was 1 MUg/L, the lowest
      exposure concentration tested. These findings demonstrate the importance of
      delayed and indirect effects of toxicant exposure. Further, the findings of this
      study are important for environmental risk assessment of POPs in the Southern
      Ocean ecosystem and strongly highlight the significance of developmental
      endpoints for ecotoxicological testing.

PMID- 21962598
TI  - Uncommon cause of painful defecation.

PMID- 21962599
TI  - Carrier frequency of a common mutation of carnitine palmitoyltransferase 1A
      deficiency and long-term follow-up in Finland.
AB  - OBJECTIVE: To assess the long-term clinical course of carnitine
      palmitoyltransferase 1A (CPT1A) deficiency, caused by the c.1364A>C (p.K455T)
      mutation, and the carrier frequency of this mutation in Finland. STUDY DESIGN:
      This was a long-term follow-up of patients in whom the common mutation was
      detected. RESULTS: Between 1999 and 2010, 6 cases of CPT1A deficiency were
      diagnosed and treated with a high-carbohydrate, low-fat diet. The patients
      experienced their first symptoms during the first years of life, provoked by
      viral illness and/or fasting. The clinical features included hypoketotic
      hypoglycemia, hepatopathy, and loss of consciousness, ranging from transient
      unconsciousness to prolonged hyperlipidemic coma. Five cases carried a homozygous
      c.1364A>C (p.K455T) mutation, whereas 1 case had a compound c.1364A>C/c.1493A>C
      (p.Y498S) mutation. During dietary therapy, the patients had few transient
      decompensations. No carriers of mutation c.1364A>C were detected by
      minisequencing of 150 control samples. CONCLUSION: Even though CPT1A deficiency
      may be life-threatening and lead to prolonged coma, the long-term prognosis is
      good. A genotype-phenotype correlation implies that the mutations detected are
      disease-causing. Despite Finland's location close to the Arctic polar region, the
      carrier frequency of the c.1364A>C mutation in Finland is far lower than that of
      the variants found in Alaskan, Canadian, and Greenland native populations.

PMID- 21962600
TI  - Chest wall Ewing sarcoma presenting as abdominal pain in a 12-year-old boy.

PMID- 21962601
TI  - Clinical predictors and institutional variation in home oxygen use in preterm
      infants.
AB  - OBJECTIVE: To assess home oxygen use in preterm infants, identify risk factors
      predicting home oxygen use, and quantify the extent of institutional variation in
      home oxygen use across neonatal intensive care units. STUDY DESIGN: We conducted
      a retrospective cohort analysis of surviving infants of 23- to 31-week
      gestational age discharged home in 2009, with de-identified electronic medical
      record information from the Pediatrix Clinical Data Warehouse. Mixed-effects
      logistic regression quantified clinical risk factors and institutional variation
      affecting home oxygen use. RESULTS: A total of 8167 infants were identified. Home
      oxygen use varied by gestational age, from 59% of infants 23 to 24 weeks
      gestational age to 7% of infants 29 to 31 weeks gestational age. Other risk
      factors included small for gestational age, congenital anomalies, mechanical
      ventilation in the first 72 hours, fraction of inhaled oxygen >0.4 in the first
      72 hours, and patent ductus arteriosus. After adjusting for clinical risk
      factors, there was still a 4- to 5-fold difference in institutions' odds of home
      oxygen use. CONCLUSIONS: Home oxygen use was common in infants of earlier
      gestational ages and infants with more severe respiratory illness. Institutional
      variation accounted for 4- to 5-fold variation in home oxygen use. Families
      should be counseled about the likelihood of home oxygen use, and prospective
      research must identify optimal treatment strategies for high-risk infants.

PMID- 21962602
TI  - General ultrasound screening reduces the rate of first operative procedures for
      developmental dysplasia of the hip: a case-control study.
AB  - OBJECTIVES: To assess the effectiveness of general ultrasound screening to
      prevent first operative procedures of the hip. STUDY DESIGN: We conducted a case
      control study in a population in which general ultrasound screening supplementing
      clinical screening is recommended and offered free of charge for all children.
      Participation in ultrasound screening before week 7 as recommended in Germany was
      the exposure of interest. Case ascertainment was based on active surveillance in
      orthopedic hospitals. The case definition was: first operative procedure for
      developmental dysplasia of the hip (closed reduction, open reduction, or
      osteotomy) in children >9 weeks old and <5 years old and born between 1996 and
      2001. Control subjects from the same birth cohorts were recruited in telephone
      surveys. RESULTS: Cases of first operative procedures for developmental dysplasia
      of the hip (n = 446) were compared with 1173 control subjects for ultrasound
      screening. Effectiveness of ultrasound screening to prevent first operative
      procedures for developmental dysplasia of the hip was estimated as 52% (95% CI,
      32-67). Effectiveness did not vary substantially for closed and open reductions
      and osteotomy. CONCLUSIONS: General ultrasound screening reduces the rate of
      operative procedures for developmental dysplasia of the hip; the impact on
      developmental dysplasia of the hip. Treatment rates and avascular necrosis need
      further assessment to balance the benefit against potential overtreatment and
      adverse effects.

PMID- 21962603
TI  - Horner's syndrome as complication of extracorporeal membrane oxygenation in a
      neonate.

PMID- 21962604
TI  - Periventricular leukomalacia and neurodevelopmental outcome.

PMID- 21962606
TI  - Scapular winging.

PMID- 21962608
TI  - Does functional brown adipose tissue play an integral role in pediatric energy
      balance and metabolism?

PMID- 21962609
TI  - Simultaneous pulmonary, cerebral and coronary emboli.

PMID- 21962610
TI  - Peripartum myocardiopathy in Lome (Togo).

PMID- 21962611
TI  - Arrhythmogenic right ventricular cardiomyopathy/dysplasia and troponin release.
      Myocarditis or the "hot phase" of the disease?

PMID- 21962612
TI  - Left ventricular torsion abnormalities in patients with obstructive sleep apnea
      syndrome: an early sign of subclinical dysfunction.
AB  - BACKGROUND: Previous echocardiographic studies using tissue Doppler imaging (TDI)
      and speckle tracking imaging (STI) have demonstrated that obstructive sleep apnea
      syndrome (OSAS) patients may develop subclinical left ventricular (LV) systolic
      and diastolic dysfunction. Our purpose was to evaluate the impact of OSAS on LV
      torsion dynamics and aortic stiffness by using TDI and STI echocardiography.
      METHODS: Forty-two patients with OSAS and no comorbidities were studied. They
      were classified into mild and severe OSAS according to the apnea-hypopnea index
      (AHI). Thirty-five healthy subjects were selected as controls. Fifteen patients
      with severe OSAS underwent chronic nocturnal nasal continuous positive airway
      pressure (CPAP) therapy. Standard echocardiographic parameters were assessed.
      Global LV longitudinal strain (LS), radial and circumferential strain were
      determined by STI. Averaged LV rotation and rotational velocities from the base
      and apex were obtained and used for calculation of LV torsion (LVtor). Mitral
      annular velocities and aortic wall velocities and strain (AoS) were also obtained
      by TDI. RESULTS: Severe OSAS had decreased LS compared with control subjects.
      LVtor increased significantly in severe OSAS compared to normals (p<.001) as a
      result of a predominant increase in apical rotation and was independently related
      to AHI and AoS in a multiple stepwise linear regression model. The group treated
      with CPAP had a significant decrease in LVtor and aortic stiffness index and
      significant increase in LS and AoS. CONCLUSIONS: LVtor, LS and AoS were
      identified as parameters demonstrating an association between LV dysfunction,
      aortic stiffness and severity of OSAS independently of other possible factors or
      comorbidities.

PMID- 21962613
TI  - PDE3 inhibition in dilated cardiomyopathy.
AB  - In dilated cardiomyopathy, a condition characterized by chamber enlargement and
      reduced myocardial contractility, decreases in beta-adrenergic receptor density
      and increases in Galphai and beta-adrenergic receptor kinase activities attenuate
      the stimulation of adenylyl cyclase in response to catecholamines. PDE3
      inhibitors have been used to 'overcome' the reduction in cAMP generation by
      blocking cAMP hydrolysis. These drugs increase contractility in the short-term,
      but long-term administration leads to an increase in mortality that correlates
      with an increase in sudden cardiac death. Whether separate mechanisms account for
      these beneficial and harmful effects, and, if so, whether PDE3 can be targeted so
      as to increase contractility without increasing mortality are questions that
      remain unanswered.

PMID- 21962614
TI  - Predictors of immune recovery and the association with late mortality while on
      antiretroviral treatment in Cambodia.
AB  - The objectives of this study were to examine the association of the on-treatment
      CD4 cell count with late mortality (after >6 months of antiretroviral treatment
      [ART]) and to identify the determinants of the long-term CD4 cell count evolution
      after treatment initiation. We conducted a retrospective analysis including all
      antiretroviral (ARV)-naive adults initiating ART in a tertiary hospital in Phnom
      Penh, Cambodia from 2003-2010. We used Cox proportional hazards modelling
      (mortality analysis), including time-updated CD4 counts, and mixed-effects
      modelling (CD4 response over time). Overall, 2840 patients were included (47%
      male, median age: 34 years, median baseline CD4 count: 78 cells/MUL). The median
      time on ART was 2.5 years (IQR 1.1-4.3); 71 patients died after >6 months of ART.
      The baseline CD4 count was the main determinant of the on-treatment CD4 cell
      count. Time-updated CD4 cell counts was the strongest determinant of late
      mortality with a HR of 0.32 (95% CI 0.16-0.63) and 0.29 (95% CI 0.11-0.71) for
      CD4 values of 200-350 cells/MUL and 350-500 cells/MUL respectively. We conclude
      that baseline CD4 counts strongly determine the long-term immune recovery, which
      critically affects late mortality. This calls for increased efforts for early ART
      initiation and availability of CD4 count testing in low-income countries.

PMID- 21962615
TI  - Norovirus prevalence in 'pathogen negative' gastroenteritis in children from
      periurban areas in Lima, Peru.
AB  - Norovirus was detected in 17.4% of 224 diarrhoeal samples from children younger
      than 24 months of age in Lima, in whom all common pathogens had been excluded
      (pathogen negative). Norovirus was identified more frequently in children older
      than 12 months of age than in younger children (34% vs 8%, P<0.001). Among
      norovirus-positive samples, genogroup II was the predominant group (92%).
      Compared with rotavirus, norovirus episodes tended to be of shorter duration and
      less severe. The role of norovirus as a cause of diarrhoea and the ascertainment
      of its severity in developing countries needs further confirmation by future
      epidemiological studies.

PMID- 21962616
TI  - Polycystic kidney disease presenting with hypertension and hypokalemia.
AB  - Hypokalemic hypertension is a common condition leading to the diagnosis of
      secondary hypertension. We report the case of a 60-year-old woman for whom the
      diagnosis of autosomal dominant polycystic kidney disease arose during the
      investigation of possible hyperaldosteronism. Activation of the renin system, as
      supported by recent studies, can explain the mechanism of hypokalemia and
      hypertension in this inherited cystic kidney disorder. Clinicians should be aware
      of this relatively uncommon clinical phenomenon of secondary hypertension in
      polycystic kidney disease. Increased understanding of the disorder's underlying
      mechanism should lay the foundation for better appreciation of potentially
      effective blood pressure treatments. The availability of a direct renin inhibitor
      may redirect research toward finding a remedy for this troublesome disease.

PMID- 21962617
TI  - Reducing infarct size with EPO in patients with ST-segment elevation myocardial
      infarction.

PMID- 21962619
TI  - Passive transport pathways for Ca(2+) and Co(2+) in human red blood cells.
      (57)Co(2+) as a tracer for Ca(2+) influx.
AB  - The passive transport of calcium and cobalt and their interference were studied
      in human red cells using (45)Ca and (57)Co as tracers. In ATP-depleted cells,
      with the ATP concentration reduced to about 1MUM, the progress curve for (45)Ca
      uptake at 1mM rapidly levels off with time, consistent with a residual Ca-pump
      activity building up at increasing [Ca(T)](c) to reach at [Ca(T)](c) about
      5MUmol(lcells)(-1) a maximal pump rate that nearly countermands the passive Ca
      influx, resulting in a linear net uptake at a low level. In ATP-depleted cells
      treated with vanadate, supposed to cause Ca-pump arrest, a residual pump activity
      is still present at high [Ca(T)](c). Moreover, vanadate markedly increases the
      passive Ca(2+) influx. The residual Ca-pump activity in ATP-depleted cells is
      fuelled by breakdown of the large 2,3-DPG pool, rate-limited by the sustainable
      ATP-turnover at about 40-50MUmol(lcells)(-1)h(-1). The apparent Ca(2+) affinity
      of the Ca-pump appears to be markedly reduced compared to fed cells. The 2,3-DPG
      breakdown can be prevented by inhibition of the 2,3-DPG phosphatase by
      tetrathionate, and under these conditions the (45)Ca uptake is markedly increased
      and linear with time, with the unidirectional Ca influx at 1mM Ca(2+) estimated
      at 50-60MUmol(lcells)(-1)h(-1). The Ca influx increases with the extracellular
      Ca(2+) concentration with a saturating component, with K(1/2(Ca)) about 0.3mM,
      plus a non-saturating component. From (45)Ca-loaded, ATP-depleted cells the
      residual Ca-pump can also be detected as a vanadate- and tetrathionate-sensitive
      efflux. The (45)Ca efflux is markedly accelerated by external Ca(2+), both in
      control cells and in the presence of vanadate or tetrathionate, suggesting efflux
      by carrier-mediated Ca/Ca exchange. The (57)Co uptake is similar in fed cells and
      in ATP-depleted cells (exposed to iodoacetamide), consistent with the notion that
      Co(2+) is not transported by the Ca-pump. The transporter is thus neither SH
      group nor ATP or phosphorylation dependent. The (57)Co uptake shows several
      similarities with the (45)Ca uptake in ATP-depleted cells supplemented with
      tetrathionate. The uptake is linear with time, and increases with the cobalt
      concentration with a saturating component, with J(max) about 16MUmol(lcells)(
      1)h(-1) and K(1/2(Co)) about 0.1mM, plus a non-saturating component. The (57)Co
      and (45)Ca uptake shows mutual inhibition, and at least the stochastic Ca(2+)
      influx is inhibited by Co(2+). The (57)Co and (45)Ca uptake are both insensitive
      to the 1,4-dihydropyridine Ca-channel blocker nifedipine, even at 100MUM. The
      (57)Co uptake is increased at high negative membrane potentials, indicating that
      the uptake is at least partially electrogenic. The (57)Co influx amounts to about
      half the (45)Ca influx in ATP-depleted cells. It is speculated that the basal
      Ca(2+) and Co(2+) uptake could be mediated by a common transporter, probably with
      a channel-like and a carrier-mediated component, and that (57)Co could be useful
      as a tracer for at least the channel-like Ca(2+) entry pathway in red cells,
      since it is not itself transported by the Ca-pump and, moreover, is effectively
      buffered in the cytosol by binding to hemoglobin, without interfering with Ca(2+)
      buffering. The molecular identity of the putative common transporter(s) remains
      to be defined.

PMID- 21962620
TI  - Introduction.

PMID- 21962618
TI  - Therapeutic response to vasoconstrictors in hepatorenal syndrome parallels
      increase in mean arterial pressure: a pooled analysis of clinical trials.
AB  - BACKGROUND: Vasoconstrictor therapy has been advocated as treatment for
      hepatorenal syndrome (HRS). Our aim was to explore across all tested
      vasoconstrictors whether achievement of a substantial increase in arterial blood
      pressure is associated with recovery of kidney function in HRS. STUDY DESIGN:
      Pooled analysis of published studies identified by electronic database search.
      SETTING & POPULATION: Data pooled across 501 participants in 21 studies.
      SELECTION CRITERIA FOR STUDIES: Human studies evaluating the efficacy of a
      vasoconstrictor administered for 72 hours or longer in adults with HRS type 1 or
      2. INTERVENTION: Vasoconstrictor therapy. OUTCOMES & MEASUREMENTS: Cohorts' mean
      arterial pressure (MAP), serum creatinine level, urinary output, and plasma renin
      activity (PRA) at baseline and subsequent times during treatment. Linear
      regression models were constructed to estimate mean daily changes in MAP, serum
      creatinine level, urinary output, and PRA for each study subgroup. Correlations
      were used to assess for association between variables. RESULTS: An increase in
      MAP is associated strongly with a decrease in serum creatinine level, but is not
      associated with an increase in urinary output. Associations were stronger when
      analyses were restricted to randomized clinical trials and were not limited to
      cohorts with either lower baseline MAP or lower baseline serum creatinine level.
      Most studies tested terlipressin as vasoconstrictor, whereas fewer studies tested
      ornipressin, midodrine, octreotide, or norepinephrine. Excluding cohorts of
      participants treated with terlipressin or ornipressin did not eliminate the
      association. Furthermore, a decrease in PRA correlated with improvement in kidney
      function. LIMITATIONS: Studies were not originally designed to test our question.
      We lacked access to individual patient data. CONCLUSIONS: An increase in MAP
      during vasoconstrictor therapy in patients with HRS is associated with
      improvement in kidney function across the spectrum of drugs tested to date. These
      results support consideration for a goal-directed approach to the treatment of
      HRS.

PMID- 21962621
TI  - The scope of the problem: the epidemiology of late preterm and early-term birth.
AB  - Late preterm birth (defined as birth between 34 0/7 to 36 6/7 weeks gestation)
      and early-term birth (defined as birth between 37 0/7 to 38 6/7 weeks gestation)
      have become the topic of much recent literature and discussion as the morbidity
      associated with delivery at these gestational ages becomes evident. Although
      infants delivered during this time period remain at relatively low risk for
      complications, the rate of morbidities in this group, particularly as it relates
      to respiratory function, is increased several-fold when they are compared to
      infants delivered at 39 weeks. The following article reviews the morbidities and
      mortality associated with both late preterm and early-term birth, as well
      available data on long-term outcomes of neonates born at these gestational ages.

PMID- 21962622
TI  - Timing of delivery for women with stable placenta previa.
AB  - Women with placenta previa are at increased risks for complications related to
      obstetrical hemorrhage and the need for emergent delivery. Some will remain
      asymptomatic without preterm labor or vaginal bleeding, and thus the clinician
      must decide when to schedule cesarean delivery in a "stable" patient. Decision
      making for the optimal timing of delivery across the late preterm and early-term
      period requires balancing the probability and severity of maternal hemorrhage at
      each gestational age versus the probability and severity of neonatal morbidity.
      On the basis of the limited available data, in women with uncomplicated complete
      placenta previa, scheduled delivery between 36 and 37 weeks should be considered.

PMID- 21962623
TI  - Indicated preterm birth for placenta accreta.
AB  - The purpose of this article is to review the risks and benefits of scheduled
      preterm delivery in patients with placenta accreta, increta, and percreta and to
      provide guidance regarding timing of delivery in such cases. Relevant documents
      for this opinion were identified through a search of the English literature for
      publications, including one or more of the keywords "accreta" or "increta" or
      "percreta" and "preterm" and "delivery time" by the use of PubMed (U.S. National
      Library Of Medicine, January 1990-January 2010), with results limited to studies
      involving humans. Additional information was obtained from references identified
      from within selected articles, from additional review articles, and from
      guidelines by organizations, including the American College of Obstetricians &
      Gynecologists. Each included article was evaluated according to study design and
      quality in accordance with scheme outlined by the U.S. Preventative Services Task
      Force, and final recommendations are provided based on the level of published
      evidence. On the basis of this search, we found that abnormal placentation,
      encompassing placenta accreta, increta, and percreta, is increasingly common. We
      also found that randomized controlled trials and well-controlled observational
      studies that can be used to define best practice in delivery time are lacking.
      Optimal delivery time must be determined from available case series,
      retrospective reviews and decision analysis studies. Given the best-available
      evidence, optimal time for delivery is believed to be between 34 and 35 weeks in
      most cases.

PMID- 21962624
TI  - Optimal timing and mode of delivery after cesarean with previous classical
      incision or myomectomy: a review of the data.
AB  - Uterine rupture is an obstetrical emergency that can be catastrophic for the
      mother and fetus. Previous uterine surgery, including previous cesarean delivery
      or myomectomy, is an established risk factor, although the exact magnitude of the
      associated risk remains uncertain. We reviewed the literature related to uterine
      rupture after previous cesarean delivery with classical incision or myomectomy in
      an attempt to quantify outcomes associated with various management strategies.
      Although cesarean delivery with a classical incision is relatively uncommon
      (representing 0.3%-0.4% of deliveries), it presents a significant risk of rupture
      in subsequent pregnancies (1%-12% on the basis of published reports). Available
      data suggest that scheduled cesarean at 36-37 weeks optimizes both maternal and
      fetal outcomes in these cases. Patients with previous myomectomy are more
      frequently encountered in the obstetrical population. The risk of uterine rupture
      in subsequent pregnancies in these women is substantially lower than those with a
      history of previous classical incision (0.5%-0.7% on the basis of published
      reports). Although less common, given the potentially devastating consequences of
      uterine rupture, scheduled delivery at 38 weeks is suggested in those women
      requiring cesarean delivery. Despite the lack of well-controlled studies,
      preferred management strategies can be gleaned from previously published data to
      optimize maternal and fetal outcomes in women with these risk factors.

PMID- 21962625
TI  - Timing delivery of the growth-restricted fetus.
AB  - Intrauterine growth restriction (IUGR) is commonly defined as an estimated fetal
      weight of less than the 10th percentile. While 70% of these are small for normal
      reasons and not at risk, 30% are pathologically small at risk for numerous
      complications including fetal death. In the late preterm IUGR fetus (>34 weeks),
      prematurity risks less and the risk of fetal demise becomes the primary concern.
      Pulsed-wave Doppler interrogation of the umbilical and middle cerebral artery is
      useful in reducing perinatal mortality, however, Doppler changes in these vessels
      of the IUGR fetus may not occur after 34 weeks gestation. There are no randomized
      trials addressing the timing of delivery of the IUGR fetus in the late preterm or
      early-term period. However, retrospective reports show an increase risk of fetal
      demise. While timing the delivery of the late preterm/early-term IUGR fetus
      requires consideration of multiple factors (e.g. degree of growth restriction,
      etiology, amniotic fluid volume, and biophysical and Doppler testing), available
      data suggests that delivery should occur by 37 to 38 weeks for singleton IUGR
      fetuses. In twin pregnancies with a co-twin IUGR fetus, chorionicity also impacts
      timing of delivery, but delivery should occur by 34-36 weeks.

PMID- 21962626
TI  - Indicated preterm birth for fetal anomalies.
AB  - Between 2% and 3% of pregnancies are complicated by fetal anomalies. For most
      anomalies, there is no advantage to late preterm or early-term delivery. The
      risks of maternal or fetal complication are specific for each anomaly. Very few
      anomalies pose potential maternal risk. Some anomalies carry ongoing risks to the
      fetus, such as an increased risk of fetal death, hemorrhage, or organ damage. In
      a limited number of select cases, the advantages of late preterm or early-term
      birth may include avoiding an ongoing risk of fetal death related to the anomaly,
      allowing delivery in a controlled setting with availability of subspecialists and
      allowing direct care for the neonate with organ injury. The optimal gestational
      age for delivery cannot be determined for all pregnancies complicated by fetal
      anomalies. For most pregnancies complicated by anomalies, there is no change to
      obstetrical management regarding timing of delivery. For those that may benefit
      from late preterm or early-term delivery, variability exists such that each
      management plan should be individualized.

PMID- 21962627
TI  - Multiple gestations: timing of indicated late preterm and early-term births in
      uncomplicated dichorionic, monochorionic, and monoamniotic twins.
AB  - In this work we review the indications for late preterm and early-term birth in
      uncomplicated dichorionic, monochorionic, and monoamniotic twin gestations.
      Uncomplicated dichorionic twins have optimal outcomes when delivered at 38 weeks'
      gestation. Monochorionic twins, however, are at greater risk for unexpected
      stillbirth, and a management plan of late preterm delivery (34-37 weeks) after
      informed consent is reasonable. Monoamniotic twins are at even greater risk for
      sudden intrauterine fetal demise, and it is recommended that these expectant
      mothers be managed by inpatient hospitalization with fetal testing 1-3 times per
      day and delivery between 32 and 34 weeks' gestation. Recommendations are also
      provided for the circumstance of single intrauterine fetal demise in a twin
      gestation.

PMID- 21962628
TI  - The role of amniotic fluid assessment in indicated preterm delivery.
AB  - Measuring amniotic fluid pockets with ultrasound is an efficient and reasonably
      reliable method of evaluating amniotic fluid volume and categorizing relative
      risk of perinatal morbidity. The most commonly used ultrasound criteria for
      oligohydramnios, SDP <2 cm and AFI <5 cm, assign approximately 2%-3% and 4%-5% of
      late preterm pregnancies into the "low amniotic fluid" category. The AFI offers
      somewhat greater sensitivity and greater precision but has less specificity for
      predicting perinatal morbidity than does the SDP. Thus, before 34 weeks, use of
      the AFI <5 cm as a criterion for intensive fetal monitoring, but not as sole
      criteria for delivery, is recommended. In pregnancies beyond 34 weeks, use of
      either AFI or SDP to diagnose oligohydramnios can be expected to reliably
      identify fetuses at risk for compromised perinatal outcome especially if
      replicate measurements are confirmatory. In such cases, care must be taken to
      identify comorbid conditions that, together with oligohydramnios, may place the
      fetus at significant risk. In such cases, delivery is the recommended
      intervention.

PMID- 21962629
TI  - Management of late preterm and early-term pregnancies complicated by mild
      gestational hypertension/pre-eclampsia.
AB  - Gestational hypertension/pre-eclampsia is the most frequent obstetrical
      complication, complicating 26%-29% of all gestations in nulliparous women. In
      general, the diagnosis of mild gestational hypertension/pre-eclampsia is made at
      38 weeks or more in approximately 80% of cases. For many years, the optimal
      timing of delivery for patients with mild gestational hypertension/pre-eclampsia
      at 37-0/7 to 39-6/7 weeks was unclear. Recently, investigators of the HYPITAT
      (Pregnancy-induced hypertension and pre-eclampsia after 36 weeks: induction of
      labor versus expectant monitoring: A comparison of maternal and neonatal outcome,
      maternal quality of life and costs) randomized trial evaluated maternal and
      neonatal complications in patients at 36-40 weeks' gestation who were randomized
      to either induction of labor or expectant monitoring. The results of this trial
      revealed that induction of labor at or after 37-0 weeks was associated with lower
      rate of maternal complications without increased rates of either cesarean
      delivery or neonatal complications. In contrast, the optimum management for those
      with mild hypertension/pre-eclampsia with stable maternal and fetal conditions at
      34-0/7 to 36-6/7 weeks remains uncertain. Therefore, there is urgent need for
      research to evaluate the reasons for late preterm birth in such women as well as
      for a randomized trial to evaluate the optimal timing for delivery in such
      patients.

PMID- 21962630
TI  - Timing of indicated late preterm and early-term birth in chronic medical
      complications: diabetes.
AB  - The number of pregnant women who have type 2 diabetes and the number found to
      have gestational diabetes are progressively increasing. In the future, as many as
      20% of pregnant women may be diagnosed with diabetes. Although there is consensus
      regarding many issues in the treatment of pregnant women with diabetes, there are
      few evidenced-based studies upon which to base the timing of delivery. There must
      be a balance between increased neonatal morbidity of late preterm and early-term
      delivery and fetal mortality. Potential adverse outcomes associated with late
      preterm and early-term delivery include respiratory problems as well as other
      metabolic dysfunctions characteristic of the preterm infant of a mother with
      diabetes. Delivery at term increases the risk of fetal demise, fetal overgrowth,
      and birth injury. Even among diabetic women who practice good glycemic control,
      the risk of intrauterine fetal demise in third trimester appears greater than
      that of neonatal death. Additional prospective data are urgently needed to better
      understand the short and long-term risks and benefits of the timing of delivery
      in this very common obstetrical dilemma.

PMID- 21962631
TI  - Previous stillbirth, late preterm, and early-term birth.
AB  - Subsequent pregnancies are emotionally traumatic for families with previous
      stillbirths. Such pregnancies have a 2- to 10-fold increase in the risk for
      stillbirth as well as an increased probability of other adverse obstetrical
      outcomes. These medical risks as well as anxiety on the part of families and care
      providers contribute to an increase in late preterm and early-term birth.
      However, delivery before 39 weeks' gestation has not been proven to reduce the
      risk of recurrent stillbirth or adverse pregnancy outcomes in women with previous
      stillbirths. This work reviews data regarding the optimal timing of delivery in
      subsequent pregnancies after previous stillbirth, as well as for patients at risk
      from stillbirth in general. Management recommendations from current data are
      presented and knowledge gaps are highlighted.

PMID- 21962632
TI  - Spontaneous late preterm births: what can be done to improve outcomes?
AB  - Despite the increase in indicated late preterm births, spontaneous preterm labor
      and preterm premature rupture of the fetal membranes are the most common
      antecedent diagnoses leading to births between 34-0/7 and 36-6/7 weeks of
      gestation. Regional and institutional variation in the rates of late spontaneous
      preterm birth suggests that there may be opportunities to reduce the number of
      these births. This article summarizes the factors contributing to late
      spontaneous preterm birth and offers suggestions to improve care for these
      mothers and infants.

PMID- 21962633
TI  - Postoperative radiographs after maxillofacial trauma: Sense or nonsense?
AB  - The purpose of the present study was to investigate the necessity of routine
      postoperative radiographic analysis in patients with maxillofacial trauma.
      Between January 2000 and January 2010, 579 patients were treated surgically for
      646 maxillofacial fractures including complex maxillofacial trauma. The incidence
      of surgical retreatments based on postoperative radiographs after maxillofacial
      trauma were investigated. 16 patients needed surgical retreatment. The decision
      to revise was based on postoperative imaging alone in one patient (0.2%). The
      available data in the literature concerning postoperative radiography in
      maxillofacial trauma was reviewed. Six useful studies concerning postoperative
      radiography in maxillofacial trauma were available for review. When combining
      these studies a total of 1377 patients underwent surgery for correction of a
      maxillofacial fracture. Nine patients returned to the operating theatre for
      correction of the initial procedure after trauma (0.7%). The present results are
      in line with the available literature. Routine postoperative radiography is not
      necessary after surgical treatment of maxillofacial trauma. Avoiding routine
      postoperative radiography will lead to a reduction in exposure of patients to
      ionizing radiation, a reduction of costs and probably a more efficient discharge.

PMID- 21962634
TI  - Specific serum antibody responses in channel catfish (Ictalurus punctatus)
      provide limited protection against Streptococcus ictaluri challenge.
AB  - Passive immunization studies were conducted to determine the role of specific
      antibodies in immunity to Streptococcus ictaluri. Adult channel catfish
      (Ictalurus punctatus) were injected i.p. with tryptic soy broth as control or
      with 1.5 * 10(7)colony-forming units (cfu) S. ictaluri/fish at 0, 30, and 60 d,
      and serum was collected 90 d after the original challenge. Fish were passively
      immunized by i.p. injection with serum from the tryptic soy broth (TSB) control
      group, anti-S. ictaluri serum from fish immunized three times and sampled at 90 d
      (SSI), or heat-inactivated anti-S. ictaluri serum from fish immunized three times
      and sampled at 90 d (HISSI). These passively immunized fish were then challenged
      72 h later with 1.5 * 10(8)cfu S. ictaluri/fish. Over 21 d, the mean cumulative
      percent survival was 43.3 (TSB), 63.3 (SSI), and 50.0 (HISSI). A significant
      difference in cumulative percent survival was noted between the TSB and the HISSI
      groups, and significant differences were noted between these groups and the SSI
      group. Serum obtained from immunized fish 72 h after passive immunization
      exhibited increased anti-S. ictaluri antibody levels. Twenty-one days after the
      challenge, the HISSI and SSI group antibody levels significantly increased above
      their corresponding pre-challenge levels. No significant (r(2)=0.0806; P<0.5985)
      correlation between increased pre-challenge specific serum antibody levels and
      survival after challenge was demonstrated when analyzing the control and passive
      immunization groups. The results indicate that both specific anti-S. ictaluri
      antibodies and non-specific immune responses are important for protection against
      S. ictaluri.

PMID- 21962635
TI  - Immunogold labeling of carbonic anhydrase isozyme (CA-VI) in secretory granules
      of human parotid glands.
AB  - Serous granules in the human parotid gland have a well-defined substructure,
      consisting of a dense spherule suspended in a moderately dense matrix. Immunogold
      labeling with an antibody against carbonic anhydrase VI revealed that this enzyme
      is localized within the matrix and is absent from the spherule. This location
      matches that of a number of other salivary gland proteins. Cell organelles
      involved in the secretory pathway are devoid of label. Labeling was not observed
      in any ductular component of the gland.

PMID- 21962636
TI  - Conditioned medium from hypoxia-treated adipocytes renders muscle cells insulin
      resistant.
AB  - Adipose tissue hypoxia is an early phenotype in obesity, associated with
      macrophage infiltration and local inflammation. Here we test the hypothesis that
      adipocytes in culture respond to a hypoxic environment with the release of pro
      inflammatory factors that stimulate macrophage migration and cause muscle insulin
      resistance. 3T3-L1 adipocytes cultured in a 1% O2 atmosphere responded with a
      classic hypoxia response by elevating protein expression of HIF-1alpha. This was
      associated with elevated mRNA expression and peptide release of cytokines
      TNFalpha, IL-6 and the chemokine monocyte chemoattractant protein-1 (MCP-1). The
      mRNA and protein expression of the anti-inflammatory adipokine adiponectin was
      reduced. Conditioned medium from hypoxia-treated adipocytes (CM-H), inhibited
      insulin-stimulated and raised basal cell surface levels of GLUT4myc stably
      expressed in C2C12 myotubes. Insulin stimulation of Akt and AS160
      phosphorylation, key regulators of GLUT4myc exocytosis, was markedly impaired. CM
      H also caused activation of JNK and S6K, and elevated serine phosphorylation of
      IRS1 in the C2C12 myotubes. These effects were implicated in reducing propagation
      of insulin signaling to Akt and AS160. Heat inactivation of CM-H reversed its
      dual effects on GLUT4myc traffic in muscle cells. Interestingly, antibody
      mediated neutralization of IL-6 in CM-H lowered its effect on both the basal and
      insulin-stimulated cell surface GLUT4myc compared to unmodified CM-H. IL-6 may
      have regulated GLUT4myc traffic through its action on AMPK. Additionally,
      antibody-mediated neutralization of MCP-1 partly reversed the inhibition of
      insulin-stimulated GLUT4myc exocytosis caused by unmodified CM-H. In Transwell co
      culture, hypoxia-challenged adipocytes attracted RAW 264.7 macrophages,
      consistent with elevated release of MCP-1 from adipocytes during hypoxia.
      Neutralization of MCP-1 in adipocyte CM-H prevented macrophage migration towards
      it and partly reversed the effect of CM-H on insulin response in muscle cells. We
      conclude that adipose tissue hypoxia may be an important trigger of its
      inflammatory response observed in obesity, and the elevated chemokine MCP-1 may
      contribute to increased macrophage migration towards adipose tissue and
      subsequent decreased insulin responsiveness of glucose uptake in muscle.

PMID- 21962637
TI  - Cold shock Y-box protein-1 participates in signaling circuits with auto
      regulatory activities.
AB  - The cold shock protein Y-box (YB) binding-1 is an example of a highly regulated
      protein with pleiotropic functions. Besides activities as a transcription factor
      in the nucleus or regulator of translation in the cytoplasm, recent findings
      indicate extracellular effects and secretion via a non-classical secretion
      pathway. This review summarizes regulatory pathways in which YB-1 participates,
      all iterating auto-regulatory loops. Schematics are developed that elucidate the
      cold shock protein activities in (i) fine-tuning its own expression level
      following platelet-derived growth factor-B-, thrombin- or interferon-gamma
      dependent signaling, (ii) as a component of the messenger ribonucleoprotein
      (mRNP) complex for interleukin-2 synthesis in T-cell commitment/activation, (iii)
      pro-fibrogenic cell phenotypic changes mediated by transforming growth factor
      beta, and (iv) receptor Notch-3 cleavage and signal transduction. Emphasis is put
      forward on subcellular protein translocation mechanisms and underlying signaling
      pathways. These have mostly been analysed in cell culture systems and rarely in
      experimental models. In sum, YB-1 seems to fulfill a pacemaker role in diverse
      diseases, both inflammatory/pro-fibrogenic as well as tumorigenic. A clue towards
      potential intervention strategies may reside in the understanding of the outlined
      auto-regulatory loops and means to interfere with cycling pathways.

PMID- 21962638
TI  - [Sleep disorders in chronic renal failure].
AB  - Sleep disorders are common in patients with chronic renal failure (CRF),
      especially in those receiving hemodialysis. Sleep-related complaints in this
      patient population may include insomnia, daytime sleepiness or fatigue and
      depression. In addition to causing impairment of daytime function and quality of
      life, sleep apnea may also increase the cardiovascular morbidity and mortality,
      especially in dialysis patients. In CRF patients, an increased prevalence of
      sleep apnea, restless legs syndrome and periodic limb movement during sleep has
      been reported. Epidemiology, pathophysiology and treatment of sleep disorders in
      CRF and dialysis patients are still unclear and require further research.

PMID- 21962639
TI  - [Interest of a specific programme in patient education for dialysis in out-center
      patients].
AB  - The development of therapeutic patient education for dialysis patients is recent
      and concerns mainly out-center patients. To our knowledge, only two papers
      centred on therapeutic education with out-center patients have been published.
      The particularities of this dialysis modality (unit close to the home, more
      autonomy, a nurse for six patients, organisation of unit, better quality of life
      and psychological status) highlight the interest to develop specific educational
      programs for patients treated in out-center sitting. The example of a program in
      Aquitaine (France) composed of mainly collective sessions (representations of the
      disease, dietetic recommendations, hygiene and protection of the vascular access,
      drugs compliance...) allows to propose several practical implications to initiate
      the development of specific programs in therapeutic education for out-center
      dialysis: educative sessions during the sessions of dialysis, group patients,
      multidisciplinary team, evaluation of the program from a medical and psychosocial
      point of view...

PMID- 21962640
TI  - Analytical Chemistry, a great success despite the unfortunate divisions in
      academic departments.

PMID- 21962641
TI  - On some trends.

PMID- 21962642
TI  - Increasing demands on analytical chemistry and chemical analysis.

PMID- 21962643
TI  - Laboratorial diagnosis of paracoccidioidomycosis and new insights for the future
      of fungal diagnosis.
AB  - Paracoccidioidomycosis (PCM) is the most prevalent mycosis in Latin-America. As
      for other mycosis, its importance of has been largely underestimated, partially
      due to the limited geographical distribution of the etiologic fungal agent
      (Paracoccidioides brasiliensis). However, the advent of AIDS and other immune
      suppressing conditions is creating an emergent need for improved diagnostic tests
      envisaging simpler, cheaper, faster and more sensitive and accurate detection of
      pathogenic fungi, especially those causing systemic and opportunistic diseases.
      Routine laboratorial diagnosis of PCM disease relies mainly on direct observation
      of the fungus. However, culture growing is slow and, too often, definite
      diagnosis can only be obtained at later growing stages. Immunodiagnosis is also
      widely employed, although usually cumbersome and complex. Enzyme-based
      immunoassays are more amenable to automation for high-throughput testing, but may
      lead to cross-reactivity with other fungi. Plus, molecular diagnosis relying on
      polymerase-chain reaction (PCR) and nucleic-acid hybridization, although still at
      early stages of application to routine diagnosis of P. brasiliensis, has
      triggered the development of techniques for its improved specific detection, thus
      contributing for epidemiological studies as well. In the future, microarrays and
      newer biosensing technologies, coupled to new bionanotechnological tools, will
      certainly improve diagnosis of PCM and other mycosis through very specific and
      sensitive pathogen biomolecular detection.

PMID- 21962644
TI  - Analysis of anticancer drugs: a review.
AB  - In the last decades, the number of patients receiving chemotherapy has
      considerably increased. Given the toxicity of cytotoxic agents to humans (not
      only for patients but also for healthcare professionals), the development of
      reliable analytical methods to analyse these compounds became necessary. From the
      discovery of new substances to patient administration, all pharmaceutical fields
      are concerned with the analysis of cytotoxic drugs. In this review, the use of
      methods to analyse cytotoxic agents in various matrices, such as pharmaceutical
      formulations and biological and environmental samples, is discussed. Thus, an
      overview of reported analytical methods for the determination of the most
      commonly used anticancer drugs is given.

PMID- 21962645
TI  - Biosorption: a new rise for elemental solid phase extraction methods.
AB  - Biosorption is a term that usually describes the removal of heavy metals from an
      aqueous solution through their passive binding to a biomass. Bacteria, yeast,
      algae and fungi are microorganisms that have been immobilized and employed as
      sorbents in biosorption processes. The binding characteristics of microorganisms
      are attributed to functional groups on the surface providing some features to the
      biosorption process like selectivity, specificity and easy release. These
      characteristics turn the biosorption into an ideal process to be introduced in
      solid phase extraction systems for analytical approaches. This review encompasses
      the research carried out since 2000, focused on the employment of biosorption
      processes as an analytical tool to improve instrumental analysis. Since
      aminoacids and peptides as synthetic analogues of natural metallothioneins,
      proteins present in the cell wall of microorganisms, have been also immobilized
      on solid supports (controlled pore glass, carbon nanotubes, silica gel
      polyurethane foam, etc.) and introduced into solid phase extraction systems; a
      survey attending this issue will be developed as well in this review.

PMID- 21962646
TI  - Comparison of two aerosol-based detectors for the analysis of gabapentin in
      pharmaceutical formulations by hydrophilic interaction chromatography.
AB  - Comparison of hydrophilic interaction chromatography (HILIC) columns coupled with
      an evaporative light scattering detector (ELSD) or charged aerosol detector (CAD)
      was done for the detection of gabapentin in pharmaceutical formulations. The
      chromatographic separations were achieved on four HILIC columns: ZIC HILIC, ZIC
      pHILIC, Luna HILIC, and Atlantis HILIC. Experimental factors such as mobile phase
      composition, acetonitrile content, and mobile phase pH were evaluated. Validation
      of method was done in terms of linearity, sensitivity, accuracy, and precision.
      The performance of ELSD detection method is comparable to that of CAD. The intra
      day and inter-day variations were below 1.7% and 3.2% for CAD and 2.8%, and 3.4%
      for ELSD, respectively. In addition, detection sensitivities of ELSD, CAD, and UV
      detectors were also compared for HILIC and reversed phase (RP) modes and the
      highest sensitivities were obtained in the HILIC mode when connected with CAD and
      ELSD. The developed HILIC aerosol based detection methods were successfully
      applied to the analysis of gabapentin in commercial tablets and capsules.

PMID- 21962647
TI  - The use of a combined portable X ray fluorescence and multivariate statistical
      methods to assess a validated macroscopic rock samples classification in an ore
      exploration survey.
AB  - The combination of "ex situ" portable X ray fluorescence with unsupervised and
      supervised pattern recognition techniques such as hierarchical cluster analysis,
      principal components analysis, factor analysis and linear discriminant analysis
      have been applied to rock samples, in order to validate a "in situ" macroscopic
      rock samples classification of samples collected in the Boris Angelo mining area
      (Central Chile), during a drill-hole survey carried out to evaluate the economic
      potential of this Cu deposit. The analysed elements were Ca, Cu, Fe, K, Mn, Pb,
      Rb, Sr, Ti and Zn. The statistical treatment of the geological data has been
      arisen from the application of the Box-Cox transformation used to transform the
      data set in normal form to minimize the non-normal distribution of the data. From
      the statistical results obtained it can be concluded that the macroscopic
      classification applied to the transformed data permits at least, to distinguish
      quite well in relation to two of the rock classes defined (70.5% correctly
      classified (p<0.05)) as well as for four of the five alteration types defined "in
      situ" (75% of the total samples).

PMID- 21962648
TI  - Adsorptive stripping voltammetry of nickel with 1-nitroso-2-napthol using a
      bismuth film electrode.
AB  - A sensitive procedure is presented for the voltammetric determination of nickel.
      The procedure involves an adsorptive accumulation of nickel 1-nitroso-2-napthol
      (NN) complex on a bismuth film electrode prepared ex situ by electrodeposition.
      The most suitable operating conditions and parameters such as pH, ligand
      concentration (C(NN)), adsorptive potential (E(ads)), adsorptive time (t(ads)),
      scan rate and others were selected and the determination of nickel in aqueous
      solutions using the standard addition method was possible. The adsorbed Ni-NN
      complex gives a well defined cathodic stripping peak current at -0.70 V, which
      was used for the determination of nickel in the concentration range of 10.0-70.0
      MUg L(-1) (pH 7.5; C(NN) 6.5 MUmol L(-1); E(ads) -0.30 V; t(ads) 60s) with a
      detection limit of 0.1 MUg L(-1). The relative standard deviation for a solution
      containing 10.0 MUg L(-1) of Ni(II) was 3.5% (n=4). The proposed method was
      validated determining Ni(II) in certified reference waste water (SPS-WW1) and
      Certified Reference Water for Trace Elements (TMDA 51.3) with satisfactory
      results. Then lake water samples were analyzed.

PMID- 21962649
TI  - Optimization of the simultaneous determination of imatinib and its major
      metabolite, CGP74588, in human plasma by a rapid HPLC method using D-optimal
      experimental design.
AB  - A simple, rapid and specific HPLC method has been developed and validated for the
      simultaneous determination of imatinib, a tyrosine kinase inhibitor, and its
      major metabolite, CGP74588, in human plasma. The optimization of the HPLC
      procedure involved several variables, of which the influences of each was
      studied. After a series of preliminary-screening experiments, the composition of
      the mobile phase and the pH of the added buffer solution were set as the
      investigated variables, while the resolution between imatinib and CGP74588 peaks,
      the retention time and the imatinib peak width were chosen as the dependent
      variables. Applying D-optimal design, the optimal chromatographic conditions for
      the separation were defined. The method proved to show good agreement between the
      experimental data and predictive values throughout the studied parameter range.
      The optimum assay conditions were achieved with a ChromolithTM Performance RP-8e
      100 mm * 4.6 mm column and a mixture of
      methanol/acetonitrile/triethylamine/diammonium hydrogen phosphate (pH 6.25, 0.048
      mol L(-1)) (20:20:0.1:59.9, v/v/v/v) as the mobile phase at a flow rate of 2 mL
      min(-1) and detection wavelength of 261 nm. The run time was less than 5 min,
      which is much shorter than the previously optimized methods. The optimized method
      was validated according to FDA guidelines to confirm specificity, linearity,
      accuracy and precision.

PMID- 21962650
TI  - Molecularly bonded chitosan prepared as chiral stationary phases in open-tubular
      capillary electrochromatography: comparison with chitosan nanoparticles bonded to
      the polyacrylamide phase.
AB  - The chiral selector, chitosan (CS), was attached to the silanized capillary via a
      silane coupling agent, (3-glycidyloxypropyl)trimethoxysilane (GTS), to form the
      GTS-CS capillary, and results for this capillary were compared with those of a
      previous study on the copolymerization of CS with methacrylamide (MAA) (forming
      the MAA-CS capillary). The GTS-CS capillary did not exhibit enantioselectivity
      for d/l-tryptophan, whereas the GTS-BSA capillary, which was prepared by
      replacement of CS with bovine serum albumin (BSA), succeeded in the chiral
      separation with an Rs=2.4 in Tris buffer (50mM, pH 8.5). To increase CS
      attachment, the CS units were crosslinked by succinic acid, and the resulting GTS
      CS-s capillary phase improved the resolution to 1.9. Alternatively, the SiH-CS-s
      capillary was constructed by CS attachment on the silicon hydride phase via
      stepwise silanization and hydrosilation reactions and crosslinking by succinic
      acid, but this approach could only achieve a resolution of 1.4 in Tris buffer
      (50mM, pH 9.5). Although the GTS-CS-s and SiH-CS-s capillaries were still
      inferior to the MAA-CS capillary (Rs=3.8), the enantioselectivities of the three
      capillaries were all in the range of 1.4-1.6. For the (+/-)-catechin sample, the
      plate heights of the GTS-CS-s and SiH-CS-s capillaries conditioned in pH 8.5 Tris
      buffer with 60% MeOH modifier were 0.9 cm ((-)-catechin) and 6.0 cm ((+)
      catechin)) and 2.9 cm (-) and 3.2 cm (+), respectively, and these heights were
      comparable to the MAA-CS capillary (2.5 cm (-), 6.0 cm (+)) in pH 6.6 phosphate
      buffer with 80% MeOH. Finally, a racemate of ibuprofen, a weakly acidic anti
      inflammatory drug, was successfully baseline resolved by the GTS-CS-s and SiH-CS
      s capillaries in the borate buffers, which were 30 mM at pH 7.5 and 10mM at pH
      8.0, respectively.

PMID- 21962651
TI  - Spectrophotometric determination of titanium with o-carboxyphenylfluorone in
      cationic micellar media, and its equilibrium and kinetic studies.
AB  - Spectrophotometric determination of titanium(IV) was accomplished with o
      carboxyphenylfluorone (OCPF) in the presence of hexadecyltrimethyl ammonium
      chloride (HTAC) under strongly acidic media. In the determination of
      titanium(IV), Beer's law was obeyed in the range of 24-340 ng mL(-1) with an
      effective molar absorption coefficient (at 530 nm) and relative standard
      deviation of 2.24 * 10(5)dm(3)mol(-1)cm(-1) and 0.64% (n=8), respectively. The
      severe interference of iron ions was easily eliminated by the addition of
      ethylenediaminetetraacetic acid (EDTA); the effects of other foreign substances
      were low. Equilibrium and kinetic studies under analytical conditions were
      investigated to quantitatively evaluate the reaction mechanism. The obtained
      orange complex is considered to be Ti(OCPF)(4). Its stability log K(f) and rate
      constant K(obs) are 16.88 and 1.65 * 10(-2)s(-1), respectively. It is suggested
      that the color of the complex is related to the species of OCPF in the solution.

PMID- 21962652
TI  - Selective detection of dopamine in the presence of uric acid using a gold
      nanoparticles-poly(luminol) hybrid film and multi-walled carbon nanotubes with
      incorporated beta-cyclodextrin modified glassy carbon electrode.
AB  - Gold nanoparticles-poly(luminol) (Plu-AuNPs) hybrid film and multi-walled carbon
      nanotubes with incorporated beta-cyclodextrin modified glassy carbon electrode
      (beta-CD-MWCNTs/Plu-AuNPs/GCE) was successfully prepared for simultaneous
      determination of dopamine (DA) and uric acid (UA). The surface of the modified
      electrode has been characterized by X-ray photo-electron spectroscopy (XPS),
      energy dispersive X-ray spectroscopy (EDS), field-emission scanning electron
      microscope (SEM) and transmission electron microscope (TEM). Cyclic voltammetry
      (CV), electrochemical impedance spectroscopy (EIS) and differential pulse
      voltammetry (DPV) have been used to investigate the beta-CD-MWCNTs/Plu-AuNPs
      composite film. Gold nanoparticles anchored into poly(luminol) film exhibited
      catalytic activity for DA. MWCNTs with incorporated beta-CD can greatly promote
      the direct electron transfer. In 0.10 M phosphate buffer solution (PBS, pH 7.0),
      the DPV response of the beta-CD-MWCNTs/Plu-AuNPs/GCE sensor to DA is about 8-fold
      as compared with the Plu-AuNPs/GCE sensor, and the detection limit for DA is
      about one order of magnitude lower than the Plu-AuNPs/GCE sensor. The steady
      state current response increases linearly with DA concentration from 1.0 * 10(-6)
      to 5.6 * 10(-5)M with a low detection limit (S/N=3) of 1.9 * 10(-7)M. Moreover,
      the interferences of ascorbic acid (AA) and uric acid (UA) are effectively
      diminished. The applicability of the prepared electrode has been demonstrated by
      measuring DA contents in dopamine hydrochloride injection.

PMID- 21962653
TI  - Determination of post-culture processing with carbohydrates by MALDI-MS and TMS
      derivatization GC-MS.
AB  - Biological materials generally require stabilization to retain activity or
      viability in a dry form. A number of industrial products, such as vaccines,
      probiotics and biopesticides have been produced as dry preparations. The same
      methods and materials used for stabilizing commercial microbial products may be
      applicable to preserving biothreat pathogens in a dry form. This is a likely step
      that may be encountered when looking at samples from terrorism attempts since
      only spores, such as those from Bacillus anthracis, are inherently stable when
      dried. The stabilizers for microbial preparations generally include one or more
      small carbohydrates. Different formulations have been reported for different
      industrial products and are often determined empirically. However sugar alcohols
      (mannitol and sorbitol) and disaccharides (lactose, sucrose and trehalose) are
      the common constituents of these formulations. We have developed an analytical
      method for sample preparation and detection of these simple carbohydrates using
      two complementary analytical tools, MALDI-MS and GC-MS. The native carbohydrates
      and other constituents of the formulation are detected by MALDI-MS as a screening
      tool. A longer and more detailed analysis is then used to specifically identify
      the carbohydrates by derivatization and GC-MS detection. Both techniques were
      tested against ten different types of stabilization recipes with Yersinia pestis
      cell mass cultured on different media types used as the biological component. A
      number of additional components were included in these formulations including
      proteins and peptides from serum or milk, polymers (e.g. poly vinyl pyrrolidone -
      PVP) and detergents (e.g. Tween). The combined method was characterized to
      determine several figures of merit. The accuracy of the method was 98% for MALDI
      MS and 100% for GC-MS. The repeatability for detection of carbohydrates by MALDI
      MS was determined to be 96%. The repeatability of compound identification by GC
      MS was determined by monitoring variation in retention time, which is vital for
      identification of isomeric carbohydrates. The figures of merit illustrate an
      effective and accurate method for mono and disaccharide detection independent of
      formulation. This meets our primary goal for method development as small
      carbohydrates are among the most common stabilizers employed.

PMID- 21962654
TI  - A new flow injection preconcentration method based on multiwalled carbon
      nanotubes for the ETA-AAS determination of Cd in urine.
AB  - A new flow injection (FIA) procedure for the preconcentration of cadmium in urine
      using multiwalled carbon nanotubes (MWCNT) as sorbent and posterior
      electrothermal atomization atomic absorption spectrometry (ETA-AAS) Cd
      determination has been developed. Cadmium was retained in a column filled with
      previously oxidized MWCNTs and it was quantitatively eluted with a nitric acid
      solution. The parameters influencing the adsorption-elution process such as pH of
      the sample solution, amount of sorbent and flow rates of sample as well as eluent
      solutions have been studied. Cd concentration in the eluent was measured by ETA
      AAS under the optimized conditions obtained. The results indicated the
      elimination of urine matrix effect as a consequence of the preconcentration
      process performed. Total recovery of cadmium from urine at pH 7.2 using a column
      with 45 mg of MWCNTs as sorbent and employing a HNO(3) 0.5 mol L(-1) solution for
      elution was attained. The detection limit obtained was 0.010 MUg L(-1) and the
      preconcentration factor achieved was 3.4. The method showed adequate precision
      (RSD: 3.4-9.8%) and accuracy (mean recovery: 97.4-100%). The developed method was
      applied for the determination of cadmium in real urine samples from healthy
      people (in the range of 0.14-2.94 MUg L(-1)) with satisfactory results.

PMID- 21962655
TI  - Enhanced MCR-ALS modeling of HPLC with fast scan fluorimetric detection second
      order data for quantitation of metabolic disorder marker pteridines in urine.
AB  - This work presents the development of a liquid chromatographic method based on
      modeling entire fast scan fluorimetric detection second-order data with the
      multivariate curve resolution alternating least squares algorithm, for the
      simultaneous determination of five marker pteridines in urine samples. The
      modeling strategy involves the building of a single MCR-ALS model composed of
      matrices augmented in the spectral mode, i.e. time profiles remain invariant
      while spectra may change from sample to sample. This approach allowed us to
      separate and determine the whole analytes at once. The developed approach enabled
      us to determine five of the most important metabolic disorder marker pteridines:
      biopterin, neopterin, isoxanthopterin, pterin and xanthopterin, three of them
      presenting emission spectra with the same emission wavelength maxima. In
      addition, some of these analytes present overlapped time profiles. As a
      consequence of using the entire data sets, a considerable reduction of the data
      processing experimental time can be achieved. Results are compared with a
      previous strategy in which data were split in five different regions, and
      information about the figures of merit of the new strategy compared with the
      previously reported strategy is reported.

PMID- 21962656
TI  - Rapid and selective determination of UV filters in seawater by liquid
      chromatography-tandem mass spectrometry combined with stir bar sorptive
      extraction.
AB  - Fast liquid chromatography coupled to triple-quadrupole tandem mass spectrometry
      was employed for the determination of six UV filters in seawater. The separation
      of the analytes was achieved in less than 5 min; polarity switching was used as
      four of the analytes were ionized in positive mode and the remaining two in
      negative mode. Two ionization sources were employed and compared: atmospheric
      pressure chemical ionization (APCI) gave better results than electrospray
      ionization (ESI) for all analytes, with higher reproducibility and lower
      detection limits. Therefore APCI was chosen for the determination of the analytes
      in seawater samples using stir bar sorptive extraction-liquid desorption (SBSE
      LD). Quantitative analysis was performed in multiple reaction monitoring (MRM)
      mode; fragmentation pathways of the analytes with regard to the formation of the
      MRM ions were also proposed. For the analysis of seawater samples, calibration
      curves were drawn using SBSE in spiked seawater. All figures of merit of the
      method were satisfactory; limits of detection were particularly low for the four
      analytes ionized in positive mode, being in the range 8-31 ng/L. The method was
      applied to the determination of the six UV filters in seawater samples from
      Liguria, Italy. Only benzophenone-3 (BP-3) and ethylhexyl methoxycinnamate (EHMC)
      were measured in the analyzed samples; some of the remaining analytes were also
      detected but always below the limit of quantitation.

PMID- 21962657
TI  - Uncertainty in spectrophotometric analysis--"error propagation break up", a novel
      statistical method for uncertainty management.
AB  - In this work, is given the Combined Standard Uncertainty (CSU) calculation
      procedure, which can be applied in spectrophotometric measurements. For the
      assessment of the computations, different approaches are discussed, such as the
      contribution to the Combined Standard Uncertainty of the reproducibility, the
      repeatability, the total bias, the calibration curve, and the type of the
      measurand. Results of inter-laboratory measurements confirmed the assumptions.
      For the minimization of the errors propagation a controlled experimental
      procedure was applied by this laboratory, called "errors propagation break-up"
      (ERBs). The uncertainty of sample concentration from a reference curve dominates
      the Combined Standard Uncertainty. The contribution of the method and the
      laboratory bias (total bias) to the CSU is insignificant under controlled
      conditions of a measurement. This work develops a simple methodology that can be
      utilized to evaluate the uncertainty and errors control on routine methods used
      both by academic researchers or the industrial sector.

PMID- 21962658
TI  - Usefulness of gold nanoparticles as labels for the determination of gliadins by
      immunoaffinity chromatography with light scattering detection.
AB  - A simple and fast immunoaffinity method is proposed for the determination of
      gliadins for the first time using gold nanoparticles (AuNPs) as labels. The
      tracer used consists in a gliadin-AuNP conjugate prepared by the adsorption of
      gliadins onto the nanoparticle surface. Two AuNP sizes with diameters of 10nm and
      20 nm were assayed to compare the behaviour of the corresponding tracer in the
      assay. The method relies on the injection in a commercial Protein G column of a
      preincubated mixture containing gliadins, polyclonal anti-gliadin antibodies, and
      the gliadin-AuNP tracer. This approach allows the separation of free and bound
      tracer fractions without any additional elution step, and the direct measurement
      of the resonance light scattering intensity of the free tracer through the peak
      height of the immunochromatogram, which is proportional to the analyte
      concentration. The immunocolumn can be used up to 25 times without eluting and it
      can be regenerated for at least 20 times. The dynamic ranges of the calibration
      graphs and the detection limits are 0.5-15.0 and 1.5-15.0 MUg mL(-1) gliadins,
      and 0.2 MUg mL(-1) and 0.8 MUg mL(-1) gliadins, using 20-nm and 10-nm Au-NPs as
      labels, respectively. The precision, expressed as relative standard deviation,
      ranges between 2.7% and 2.9% using 20-nm AuNPs and 4% and 6.1% for 10-nm AuNPs.
      The method has been applied to the determination of the prolamin fraction in beer
      samples, obtaining recovery values in the range 71.2% and 101.7%.

PMID- 21962659
TI  - Simultaneous analysis of chlorophenols, alkylphenols, nitrophenols and cresols in
      wastewater effluents, using solid phase extraction and further determination by
      gas chromatography-tandem mass spectrometry.
AB  - An analytical methodology has been developed for the simultaneous extraction of
      13 phenolic compounds, including chlorophenols (CPs), nitrophenols (NTPs),
      cresols and alkylphenols (APs) in different types of wastewater (WW) effluents. A
      solid-phase extraction (SPE) method has been optimized prior to the determination
      by gas chromatography coupled to triple quadrupole tandem mass spectrometry (GC
      QqQ-MS/MS). Due to the complexity of the matrix, a comparison study of matrix
      matched-calibration (MMC) and standard addition calibration (SAC) was carried out
      for quantification purposes. The optimized procedure was validated using the SAC
      approach since it provided the most adequate quantification results (in terms of
      recovery and precision values). Recoveries were in the range 60-135% (0.5 MUg L(
      1)), 70-115% (1 MUg L(-1)), and 78-120% (5 MUg L(-1)), with precision values
      (expressed as relative standard deviation, RSD) <= 30% (except for 2-nitrophenol)
      involving intra-day and inter-day precision studies. Limits of detection (LODs)
      and quantification (LOQs) were also evaluated, and LOQs ranged from 0.03 MUg L(
      1) to 2.5 MUg L(-1). The proposed method was applied to the analysis of 8 real WW
      effluent samples, finding some phenolic compounds (e.g. 2-chlorophenol, 2,4,6
      trichlorophenol and 4-tert-octylphenol) at concentrations higher than the
      established LOQs.

PMID- 21962660
TI  - Towards multimodal HPLC separations on humic acid-bonded aminopropyl silica: RPLC
      and LEC behavior.
AB  - In the present study, metal binding property of humic acid (HA) was successfully
      adapted to the ligand-exchange concept, and metal-loaded immobilized humic acid
      was used as a ligand exchanger stationary phase for separation of some
      nucleosides. Humic-acid bonded aminopropyl silica (EC-HA-APS) was turned into
      ligand exchanger forms by loading aqueous solutions of Cu(2+), and Co(2+) to the
      column (4.6 * 150; as mm) packed with EC-HA-APS. Metal ion solutions were loaded
      to the column in a stepwise manner where the concentration of metal ion solution
      being loaded to the column was increased gradually between 5 and 100mM. The
      progress of metal loading process was monitored via the breakthrough curves
      propagated stepwise. Ligand-exchange chromatography (LEC) studies were performed
      on an HPLC system, and chromatographic behaviors of the studied nucleosides (i.e.
      uridine, Urd; thymidine, Tyd; cytidine, Cyd; adenosine, Ado; and guanosine, Guo)
      were investigated on Cu(2+) and Co(2+) loaded forms of the EC-HA-APS (Cu-EC-HA
      APS and Co-EC-HA-APS). Effect of mobile phase composition, temperature, and the
      type of metal ion loaded to the column on the retentive behaviors of the
      compounds was studied, in detail. The studied solutes exhibited mixed-mode
      RPLC/LEC behavior on the stationary phase. Metal-loaded column (M-EC-HA-APS) was
      easily regenerated into its original form, EC-HA-APS, with 98 +/- 2% metal
      recoveries, by using aqueous mixture of EDTA+NH(3) at pH=7.5. Thus, the
      stationary phase exhibited a high flexibility between RPLC and LEC modes. This
      property, also, made it possible to convert the stationary phase into various
      ligand exchanger forms by loading different metal ions. Hence, capacity and
      selectivity of the stationary phase towards the studied species was manipulated
      easily by loading different metal ions to the stationary phase. Baseline
      separation for the studied species was achieved on Cu-EC-HA-APS and Co-EC-HA-APS
      and some differentiations were observed in capacity and selectivity, depending on
      the type of metal loaded. Thus, being as the first endeavor on usability of
      immobilized HA as a ligand exchanger stationary phase, the present study is
      believed to be useful to understand multifunctional character of HA-based
      solid/stationary phases.

PMID- 21962661
TI  - Highly sensitive hydrazine chemical sensor based on mono-dispersed rapidly
      synthesized PEG-coated ZnS nanoparticles.
AB  - Monodispersed PEG-coated ZnS (P-ZnS) nanoparticles (NPs) were synthesized by
      facile microwave process and utilized as efficient electron mediators for the
      fabrication of highly sensitive hydrazine chemical sensor. The detailed
      morphological and structural properties revealed the monodispersity and good
      crystallinity for synthesized P-ZnS NPs. A high-sensitivity of ~ 89.3 MUA cm(-2)
      MUM and low limit of detection of 1.07 MUM, based on S/N ratio, were obtained for
      the fabrication of hydrazine chemical sensor based on P-ZnS NPs. To the best of
      our knowledge, this is the first report which demonstrates the utilization of P
      ZnS NPs for the fabrication of efficient hydrazine chemical sensor. By this work,
      it could be concluded that simply synthesized ZnS NPs can be used as efficient
      electron mediators for the fabrication of effective hydrazine chemical sensors.

PMID- 21962662
TI  - Cellulose microfiber functionalized with N,N'-bis (2-aminoethyl)-1,2
      ethanediamine as a solid sorbent for the fast preconcentration of Cd(II) in flow
      system analysis.
AB  - The present paper describes the synthesis of a new chemically modified cellulose
      microfiber through oxidation with sodium periodate and functionalization with
      N,N'-bis (2-aminoethyl)-1,2-ethanediamine for the fast and selective
      preconcentration of Cd(II) ions in flow system analysis. The new sorbent was
      characterized by FTIR, SEM, and surface area values. The uptake behavior of
      Cd(II) ions onto this sorbent was evaluated from kinetic data, pseudo-first-order
      and pseudo-second-order models, as well as from Langmuir, Freundlich and Langmuir
      Freundlich adsorption isotherms. The maximum sorption capacity of 4.59 mg g(-1)
      was estimated by the Langmuir-Freundlich model with fast kinetics for the
      sorption of Cd(II) described by the pseudo-second-order kinetic model. After
      characterization, the sorbent was packed in a mini-column, and a fast flow
      injection preconcentration system for Cd(II) determination by FAAS was developed.
      The best Cd(II) preconcentration condition, obtained by means of factorial design
      and response surface methodology, was achieved at pH 9.36 and a flow rate of 10
      mL min(-1) followed by elution with 1.0 mol L(-1) nitric acid. By using 78 s
      preconcentration time, fast and highly sensitive determination of Cd(II) ions
      could be achieved with a limit of quantification of 0.20 MUg L(-1),
      preconcentration factor of 26, consumption index of 0.5 mL, concentration
      efficiency of 20 min(-1), and sample throughput of 39 h(-1). The repeatability
      for 10 replicate determinations was found to be 7.8 and 2.5% for Cd(II) ion
      concentrations of 5.0 and 100.0 MUg L(-1), respectively. The new sorbent
      efficiency for the interference-free preconcentration of Cd(II) ions was assessed
      by analysis of tap, mineral and lake waters, as well as synthetic seawater and
      normal saline waters. Furthermore, complex samples, such as biological samples,
      could be analysed by the proposed method in accordance with the accuracy attested
      by analysis of certified reference materials, TORT-2 (lobster hepatopancreas),
      and DOLT-4 (dogfish liver).

PMID- 21962663
TI  - Determination of pesticides in river water using rotating disk sorptive
      extraction and gas chromatography-mass spectrometry.
AB  - The rotating disk sorptive extraction (RDSE) technique was applied to the
      determination of pesticides in aqueous samples. Pesticides of different
      polarities were considered in this study: chlorpyrifos, diazinon, fenvalarate,
      cyhalothrin, cypermethrin, lindane and malathion. The sorptive/desorptive
      behavior of the pesticides was studied using a rotating disk containing a
      polydimethylsiloxane (PDMS) phase on one of its surfaces. The analyte polarity
      was a significant factor in the extraction time; shorter extraction times were
      required for the more apolar pesticides. The optimum variables for the extraction
      of all analytes were: extraction time of 3h, sample volume of 25 mL, rotational
      velocity of the disk 1250 rpm, desorption time of 30 min using methanol. For
      pesticides with values of Log K(ow)>4, the extraction time can be reduced to 30
      min for a quantitative extraction. Under these conditions, recoveries between 76%
      and 101% were obtained for the target pesticides, and the repeatability of the
      methodology, expressed as relative standard deviation, was determined to be
      between 10% and 20%. Additionally, the limits of detection of the analytes were
      lower than 3.1 MUg L(-1). The extraction method developed using the RDSE was
      compared to a stir bar sorptive extraction (SBSE) under the same conditions. It
      can be observed that the extraction using the rotating disk offers higher
      recoveries because of its higher PDMS volume and its higher surface area to
      volume ratio that allows for improved mass transfer.

PMID- 21962664
TI  - On chip electrochemical detection of sarcoma protein kinase and HIV-1 reverse
      transcriptase.
AB  - In this study, we report a new multiplexed microchip platform exploiting a
      peptide-modified gold surface and a labeled electrochemical approach. The
      significance of the presented methodology lies in its ability to test related
      analytes, such as protein kinases and human immunodeficiency virus (HIV)
      proteins, that operate under separate mechanisms using a single device without
      interference. The technology is based on an electrochemical dual sensing mode
      that can be tuned towards monitoring separately two biochemical events, a
      biochemical reaction and a direct analyte-receptor binding. The first recognition
      process is illustrated by a sarcoma-related (Src) protein kinase which catalyzes
      phosphorylation transfer of a ferrocenoyl-phosphoryl group, from the ferrocene
      labeled adenosine triphosphate (Fc-ATP) co-substrate, to the surface-bound target
      peptide and induces a current response. On the other hand, HIV-1 reverse
      transcriptase (RT) protein binding to the surface-immobilized ferrocene-labeled
      target peptide is characterized by a modulation in the current intensity and peak
      potential. This proof-of-principle study is based on two different biosensing
      components and serves as a new platform for monitoring multiple analytes of
      interest. This allowed detection limits of 0.1 MUg mL(-1) and 50 pg mL(-1) for
      Src kinase and HIV-1 RT, respectively. The miniaturization of the electrochemical
      protein assay will have an impact in disease detection and treatment.

PMID- 21962665
TI  - Using low frequency full bottle diamagnetic screening to study collectible wine.
AB  - A low frequency nu < 30 MHz spectrometer capable of noninvasively and
      nondestructively screening the diamagnetic properties of full intact bottles of
      wine is described, and along with principal component analysis, used to compare
      and contrast sealed bottles of wine. The sensitivity of this approach to various
      ionic and molecular wine solutes is established by analyzing standard solutions.
      The successful application of this full bottle method to a library of collectible
      wine is discussed and suggests that the method can be used to identify
      counterfeit wine without violating the bottle.

PMID- 21962666
TI  - Modified interdigitated arrays by novel poly(1,8-diaminonaphthalene)/carbon
      nanotubes composite for selective detection of mercury(II).
AB  - This study describes a novel type of interdigitated arrays (IDA), microfabricated
      by electropolymerizing structured Poly(1,8-diaminonaphthalene)/functionalized
      multi-walled carbon nanotubes (PDAN/CNT) thin film onto a silicon chip for square
      wave voltammetry (SWV) multi-element heavy metal ion detection. The structure of
      PDAN/CNT was characterized by Raman, FE-SEM and AFM techniques. Analysed
      experiments reveal that the uptake of Hg(2+) by PDAN/CNT is quite specific and it
      can be used advantageously for electrochemical sensing of Hg(2+) thanks to
      original feature of (Hg(2+)/Hg(2)(2+)) redox potential with the respect to that
      of PDAN/CNT. As-developed IDA type electrode can extend its utility in other
      sensing applications.

PMID- 21962667
TI  - Evaluation of a magnetic polysulfone microcapsule containing organic modified
      montmorillonite as a novel solid-phase extraction sorbent with chlorophenols as
      model compounds.
AB  - A porous polysulfone microcapsule containing organic modified montmorillonite and
      magnetic nanoparticles (OMMT-Fe(3)O(4)@PSF) has been successfully prepared by a
      phase-inversion method and evaluated as a magnetic solid-phase extraction (MSPE)
      sorbent for clean-up and enrichment of 4-chlorophenol (4-CP) and 2-chlorophenol
      (2-CP) in aqueous samples. Compared with a microcapsule containing the
      conventional extraction sorbent C18 (C18-Fe(3)O(4)@PSF), OMMT-Fe(3)O(4)@PSF had
      much lower cost, a faster adsorption rate, and superior uptake amounts for the
      investigated analytes. The proposed microcapsule has been developed for the
      extraction of 4-CP and 2-CP from environmental water samples and their analysis
      by high-performance liquid chromatography with UV detection (HPLC-UV). Various
      parameters, such as pH, extraction time, the mass of sorbent, and the desorption
      conditions, have been evaluated and the calibration curves of the chlorophenols
      were linear (R(2) >= 0.9985) in the range from 1.01 to 104.5 ng mL(-1). The
      limits of detection at a signal-to-noise (S/N) ratio of 3 were 0.22 and 0.17 ng
      mL(-1) and the limits of quantification calculated at S/N=10 were 1.52 and 1.07
      ng mL(-1) for 2-CP and 4-CP, respectively. The recoveries of 2-CP and 4-CP from
      natural water and the treated wastewater samples were in the range of 84.4-115%
      with relative standard deviations (RSDs) lower than 7.0%. The results have
      demonstrated the suitability of the MSPE approach for the analysis of trace
      chlorophenols in aqueous samples.

PMID- 21962668
TI  - Low-temperature plasma ionization source for the online detection of indoor
      volatile organic compounds.
AB  - A simple-structure, low-power, and low-cost low temperature plasma (LTP)
      ionization source, coupled with mass spectrometry, for the online detection of
      indoor volatile organic compounds (VOCs) has been constructed in this work. Air,
      instead of noble gases, was employed as the discharging and carrier gas. And a
      custom-built AC high-voltage power supply with a total power consumption of 5 W,
      frequency of 2-4 kHz, and amplitude around 1-5 kV(p-p) was used. This LTP source
      is a soft ionization source. The initial performance of the ionization source has
      been evaluated by ionizing samples including alcohols, ketones, aldehydes and
      aromatics. These compounds cover most of the common air pollutants concerning
      people's health. It is well known that those plasmas generated by dielectric
      barrier discharge (DBD) produce significant amount of metastable species and
      electrons with mean energies greater than several electronvolt, but minimal
      fragmentation was observed in our work. Protonated ions are the dominant product
      for the VOCs detected after the ionization process. Further work has been
      conducted to confirm the detection feature of this source. The results are
      promising enough to ensure the novel LTP ionization source as an effective tool
      for the online detection of indoor VOCs.

PMID- 21962669
TI  - Separation of trace amounts of Ga and Ge in aqueous solution using nano-particles
      micro-column.
AB  - A simple and rapid analytical method for the separation of trace amounts of
      gallium and germanium from aqueous solution by solid-phase extraction with nano
      particles was developed. It was found that only Ga(III) could be quantitatively
      retained on nano-SiO(2) in the pH range of 3-4 and 8-12 while Ge(IV) was not
      adsorbed, but both Ga(III) and Ge(IV) ions could be adsorbed quantitatively on
      nano-TiO(2) within the pH range of 4-11. These two ions adsorbed by nano
      particles could be desorbed quantitatively. Effects of acidity, concentration of
      elution solution and interfering ions on the recovery of the analytes were
      systematically investigated. The sorption data could be well interpreted by the
      Langmuir model. Based on the Langmuir model equation, the monolayer adsorption
      capacity of nano-SiO(2)/nano-TiO(2) was calculated to be 4.26 mg g(-1)/19.68 mg
      g(-1) for Ga(III)/Ge(IV). Moreover, thermodynamic functions, the change of free
      energy (DeltaG(0)), enthalpy (DeltaH(0)) and entropy (DeltaS(0)) of the
      adsorption reaction were estimated for each metal ion. Experimental data were
      also evaluated in terms of kinetic characteristics of adsorption and the
      adsorption process for both metal ions followed well pseudo-second-order
      kinetics. Finally, the proposed method was applied to the determination of trace
      Ga(III) and Ge(IV) in some water samples using loaded nano-particles columns, and
      it is found that the recoveries of Ga(III) and Ge(IV) were obtained to be in the
      range of 96.4-105.0%. And the method was validated with certified reference
      material (GBW07311, GBW 07406) and the values obtained for Ga(III) and Ge(IV)
      were in good agreement with the certified values.

PMID- 21962670
TI  - (Oligo)thienyl-imidazo-benzocrown ether derivatives: synthesis, photophysical
      studies and evaluation of their chemosensory properties.
AB  - A series of novel (oligo)thienyl-imidazo-benzocrown ethers were synthesised
      through a simple method and evaluated as fluorimetric chemosensors for transition
      metal cations. Interaction with Ni(2+), Pd(2+), and Hg(2+) in ACN/DMSO solution
      (99:1) was studied by absorption and emission spectroscopy. Chemoselectivity
      studies in the presence of Na(+) were also carried out and a fluorescence
      enhancement upon chelation (CHEF) effect was observed following Hg(2+)
      complexation. Considering that most systems using fluorescence spectroscopy for
      detecting Hg(2+) are based on the complexation enhancement of the fluorescence
      quenching (CHEQ) effect, the present work represents one of the few examples for
      sensing of Hg(2+) based on a CHEF effect.

PMID- 21962671
TI  - The ability of spectrum autocorrelation models to predict the lycopene
      concentration in foods through visible spectroscopic data.
AB  - We developed a novel computerized approach based on lag-k autocorrelation
      coefficients (LCCs) and linear models (LMs) to estimate the concentration of
      lycopene in foods by the spectroscopy. The LCCs were calculated using the data
      obtained using whole visible scans from 400 to 600 nm (vide supra) of lycopene
      standards and food samples (ketchup, tomato juice and tomato sauce). The chaotic
      parameter (CP) was then transferred into a LM to estimate the concentration of
      lycopene compound. The integrated LCC/visible spectroscopy method developed can
      be considered as a satisfactory analytical technique able to estimate lycopene
      concentration in food samples in a fast accurate way, with a mean prediction
      error lower than 5.7% and a mean correlation coefficient higher than 0.957.

PMID- 21962672
TI  - Quantification of PCDD/Fs and dioxin-like PCBs in small amounts of human serum
      using the sensitive H1L7.5c1 mouse hepatoma cell line: optimization and analysis
      of human serum samples from adolescents of the Flemish human biomonitoring
      program FLEHS II.
AB  - Since the CALUX (Chemically Activated LUciferase gene eXpression) bioassay is a
      fast and inexpensive tool for the throughput analysis of dioxin-like compounds in
      a large number of samples and requires only small sample volumes, the use of this
      technique in human biomonitoring programs provides a good alternative to GC-HRMS.
      In this study, a method for the separate analysis of PCDD/Fs and dioxin-like PCBs
      (dl-PCBs) in human serum with the new sensitive H1L7.5c1 mouse hepatoma cell line
      was optimized. Sample dilution factors of 5 and 2.4 were selected for routine
      analysis of respectively the PCDD/Fs and dl-PCBs. The validation studies showed
      that repeatability and within-lab reproducibility for the quality control (QC)
      standard were within the in-house criteria. A long-term within-lab
      reproducibility of 25% for the PCDD/F fraction and 41% for the dl-PCB fraction
      for the analysis of pooled serum samples, expressed as pg BEQ/g fat, was
      determined. CALUX recoveries of the spiked procedural blanks were within the
      acceptable in-house limits of 80-120% for both fractions and the LOQ was 30.3 pg
      BEQ/g fat for the PCDD/Fs and 14.5 pg BEQ/g fat for the dl-PCBs. The GC-HRMS
      recovery of a C13-spiked pooled serum sample was between 60 and 90% for all
      PCDD/F congeners and between 67 and 82% for the non-ortho PCBs. An adequate
      separation between both fractions was found. The CALUX/GC-HRMS ratio for a pooled
      serum sample was respectively 2.0 and 1.4 for the PCDD/Fs and the dl-PCBs,
      indicating the presence of additional AhR active compounds. As expected, a
      correlation was found between human serum samples analyzed with both the new
      H1L7.5c1 cell line and the more established H1L6.1c3 cell line. The geometric
      mean CALUX-BEQ values, reported for the adolescents of the second Flemish
      Environment and Health Study (FLEHS II) recruited in 2009-2010, were 108 (95% CI:
      101-114) pg CALUX-BEQ/g fat for the PCDD/Fs and 32.1 (30.1-34.2) pg CALUX-BEQ/g
      fat for the dioxin-like PCBs.

PMID- 21962673
TI  - Utilisation of an enzyme-linked immunosorbent assay (ELISA) for determination of
      alkylphenols in various environmental matrices. Comparison with LC-MS/MS method.
AB  - Among the wide range of substances discharged continuously in the environment,
      alkylphenols became a major focus of environmental research in the last decades,
      as it was found that they possess endocrine disrupting properties. Knowledge
      about the occurrence and levels of alkylphenols in environment is critical for
      the risk assessment of these compounds on both ecosystem and human health.
      However, the analysis of traces of alkylphenols in environmental matrices is a
      very difficult task, and the suitable methods involve generally an extraction
      followed by an extensive sample clean-up before detection, steps often time
      consuming and costly. In order to reduce the analysis time, obtain a high
      throughput of analysis and thus improve work efficiency, the objective of the
      present study is to investigate the use of immunochemical technique (ELISA) for
      the determination of nonylphenol and octylphenol in soils and various kinds of
      water. To our knowledge, this is the first time that the determination of
      alkylphenols in soil using immunoassay technique is described. A methodology is
      developed, based on the combination of a single preparation step and the use of a
      simply ELISA kit. The performances of the method are compared with LC-MS/MS,
      considered as reference. The developed procedure offers the sensitivity and
      selectivity necessary for the detection of the target alkylphenols in the ng/g or
      ng/L range, and is successfully applied to the analysis of several samples.
      Results indicate that alkylphenols are quantified with concentrations in the same
      order than LC-MS/MS, meaning that ELISA may be useful not only in screening the
      samples and get a positive/negative response, but also it allows a good
      approximation of the concentrations.

PMID- 21962674
TI  - Development of a colorimetric inhibition assay for microcystin-LR detection:
      comparison of the sensitivity of different protein phosphatases.
AB  - A colorimetric protein phosphatase (PP) inhibition test for the detection of
      microcystin-LR (MC-LR) has been developed. Three PP2As, one recombinant and two
      natural versions, as well as one PP1 produced by molecular engineering, were
      tested. First, assays were performed using the enzymes in solution to compare
      their sensitivity to MC-LR. The PP2A purchased from ZEU Immunotec and PP1
      appeared more sensitive to the toxin than the other enzymes. With PP2A from ZEU
      Immunotec, the colorimetric test showed a detection limit of 0.0039 MUg L(-1) and
      an IC(50) value of 0.21 MUg L(-1). With PP1, the assay gave a detection limit of
      0.05 MUg L(-1) and an IC(50) value of 0.56 MUg L(-1). Therefore, this assay
      allowed the detection of lower microcystin-LR (MC-LR) concentrations than the
      maximum level (1 MUg L(-1)) recommended by the World Health Organisation (WHO).
      The main drawback of this PP-based approach in solution is poor enzyme
      stabilisation. To overcome this problem, enzymes were entrapped within either a
      photopolymer or an agarose gel. PP2A from ZEU Immunotec and PP1 were immobilised
      at the bottom of microwells. The agarose-based tests performed better than the
      photopolymer-based assay for all of the enzymes. Therefore, the agarose gel is a
      good candidate to replace the photopolymer, which is generally used in PP
      immobilising membranes. The assays based on enzyme-entrapping agarose gels showed
      detection limits equal to 0.17 MUg L(-1) and 0.29 MUg L(-1) with immobilised PP2A
      from ZEU and PP1, respectively. In view of these performances, these tests can
      potentially be used for monitoring water quality.

PMID- 21962675
TI  - Investigation of uranium-colloid interactions in soil by dual field-flow
      fractionation/capillary electrophoresis hyphenated with inductively coupled
      plasma-mass spectrometry.
AB  - This paper deals with the study of uranium-colloid interactions in a carbonated
      soil. The work is focused on the immediately available fraction obtained after a
      leaching process, according to a normalized batch method. In order to
      characterize the different colloidal carriers, Asymmetrical Flow Field-Flow
      Fractionation (As-Fl-FFF) coupled to different detectors (UV, Multi Angle Laser
      Light Scattering (MALLS) and Inductively coupled Plasma-Mass Spectrometry (ICP
      MS)) was used. The colloidal carriers are mainly inorganic particles (carbonated
      particles and clays) mixed with organic substances. Furthermore, dissolved and
      colloidal uranium species in the leaching solutions were monitored by Capillary
      Electrophoresis (CE) coupled to ICP-MS, in order to investigate the
      uranium/colloids interactions. According to the first results, uranium fate in
      this specific soil is controlled by sorption/desorption phenomena, strongly pH
      dependent.

PMID- 21962676
TI  - Quantification of nitrite and nitrate in seawater by triethyloxonium
      tetrafluoroborate derivatization-headspace SPME GC-MS.
AB  - Triethyloxonium tetrafluoroborate derivatization combined with direct headspace
      (HS) or SPME-gas chromatography-mass spectrometry (GC-MS) is proposed here for
      the simultaneous determination of nitrite and nitrate in seawater at micromolar
      level after conversion to their corresponding volatile ethyl-esters (EtO-NO and
      EtO-NO(2)). Isotopically enriched nitrite [(15)N] and nitrate [(15)N] are
      employed as internal standards and for quantification purposes. HS-GC-MS provided
      instrumental detection limits of 0.07 MUM NO(2)(-) and 2 MUM NO(3)(-). Validation
      of the methodology was achieved by determination of nitrite and nitrate in MOOS-1
      (Seawater Certified Reference Material for Nutrients, NRC Canada), yielding
      results in excellent agreement with certified values. All critical aspects
      connected with the potential inter-conversion between nitrite and nitrate (less
      than 10%) were evaluated and corrected for by the use of the isotopically
      enriched internal standard.

PMID- 21962677
TI  - Single-walled carbon nanotubes based quenching of free FAM-aptamer for selective
      determination of ochratoxin A.
AB  - Ochratoxin A, a toxin produced by Aspergillus ochraceus and Penicillium
      verrucosum, is one of the most abundant food-contaminating mycotoxins in the
      world. It has been classified by the International Agency for Research on Cancer
      (IARC) as a possible human carcinogen. In this paper, a sensitive and selective
      fluorescent aptasensor for ochratoxin A (OTA) detection was constructed,
      utilizing single-walled carbon nanotubes (SWNTs) as quencher which can quench the
      fluorescence of free unfolded toxin-specific aptamer attached with FAM
      (carboxyfluorescein). Without any coating materials as compared to graphene-oxide
      based sensor, we obtained the detection limit of our sensing platform based on
      SWNTs to be 24.1 nM with a linear detection range from 25 nM to 200 nM. This
      technique responded specifically to OTA without interference from other analogues
      (N-acetyl-L-phenylalanine, warfarin and OTB). It has also been verified for real
      sample application by testing 1% beer containing buffer solution spiked with a
      series of concentration of OTA.

PMID- 21962678
TI  - Development of a sensitive and selective kojic acid sensor based on molecularly
      imprinted polymer modified electrode in the lab-on-valve system.
AB  - In this work, a kojic acid electrochemical sensor, based on a non-covalent
      molecularly imprinted polymer (MIP) modified electrode, had been fabricated in
      the lab-on-valve system. The sensitive layer was synthesized by cyclic
      voltammetry using o-phenylenediamine as the functional monomer and kojic acid as
      the template. The template molecules were then removed from the modified
      electrode surface by washing with NaOH solution. Differential pulse voltammetry
      method using ferricyanide as probe was applied as the analytical technique, after
      extraction of kojic acid on the electrode. Chemical and flow parameters
      associated with the extraction process were investigated. The response recorded
      with the imprinted sensor exhibited a response in a range of 0.01-0.2 MUmol L(-1)
      with a detection limit of 3 nmol L(-1). The interference studies showed that the
      MIP modified electrode had excellent selectivity. Furthermore, the proposed MIP
      electrode exhibited good sensitivity and low sample/reagent consumption, and the
      sensor could be applied to the determination kojic acid in cosmetics samples.

PMID- 21962679
TI  - Chronoamperometric determination of lead ions using PEDOT:PSS modified carbon
      electrodes.
AB  - A new simple chronoamperometry methodology was developed for the ultrasensitive
      determination of lead ions using a PEDOT:PSS coated graphite carbon electrode.
      The polymer was directly coated on a graphite carbon electrode and characterized
      using simple cycle voltammetric measurements. The presence of lead ions induced a
      cathodic peak starting at -550 +/- 10 mV vs. Ag/AgCl, and an anodic peak starting
      at -360 +/- 10 mV vs. Ag/AgCl. Electroaccumulation of lead ions onto the
      PEDOT:PSS modified electrode was performed at -650 mV vs. Ag/AgCl for 30s in a pH
      2.2 hydrochloric acid solution. Chronoamperometry measurements were carried out
      at -350 mV vs. Ag/AgCl allowing the oxidation of accumulated lead. Using this
      method, lead ions were detected for concentrations ranging between 2.0 nmol L(-1)
      and 0.1 MUmol L(-1) (R(2)=0.999). The detection limit was calculated to be 0.19
      nmol L(-1) and the quantification limit of 0.63 nmol L(-1). The method was shown
      to be highly precise and sensitive, negligible interference was detected from
      other metal ions. The proposed method was successfully applied for the detection
      of lead ions in vegetables.

PMID- 21962680
TI  - Kinetic study of a complex triangular reaction system in alkaline aqueous-ethanol
      medium using on-line transmission FTIR spectroscopy and BTEM analysis.
AB  - The kinetics of the base-catalyzed reaction of methyl 4-hydroxybenzoate in
      aqueous-ethanol solvent medium was studied and analyzed via combined on-line
      transmission FTIR spectroscopy and Band-Target Entropy Minimization (BTEM)
      technique. This reaction is considered complex since it involves simultaneous
      hydrolysis and ethanolysis reactions of methyl 4-hydrozybenzoate (MP) to form
      ethyl 4-hydroxybenzoate (EP) as an intermediate and sodium 4-hydroxybenzoate as a
      final product. The pure component spectra of the reactive species involved in the
      reaction were reconstructed using BTEM technique. Their corresponding real
      concentrations were calculated and subsequently used for analyzing the kinetics
      of this triangular reaction system. The effects of temperature and solvent
      mixture compositions were studied. In general, the results show that the rates of
      both hydrolysis and ethanolysis reactions increase with temperature. Addition of
      ethanol to the solvent mixture also reduces the rates of the hydrolysis
      reactions. The effect of solvent mixture on the rate of ethanolysis reaction is
      more complex and influenced by at least two competing factors, namely the
      concentration of ethoxide ion in the solution and the stabilization effect on the
      reactant. The enthalpy and entropy activation parameters, DeltaH(?) and
      DeltaS(?), of both the hydrolysis and ethanolysis reactions were determined using
      the Eyring equation and the activation parameters confirm the associative nature
      in the elementary steps in these reactions. Finally, it is shown that the
      dominant synthetic pathway in this triangular system changes from direct
      hydrolysis of methyl 4-hydrozybenzoate to the indirect pathway via ethanolysis
      and then hydrolysis depending on the solvent mixture composition.

PMID- 21962681
TI  - Development of an autonomous detector for sensing of nerve agents based on
      functionalized silicon nanowire field-effect transistors.
AB  - The ability to detect minute traces of chemical warfare agents is mandatory both
      for military forces and homeland security. Various detectors based on different
      technologies are available but still suffer from serious drawbacks such as false
      positives. There is still a need for the development of innovative reliable
      sensors, in particular for organophosphorus nerve agents like Sarin. We report
      herein on the fabrication of a portable, battery-operated, microprocessor-based
      prototype sensor system relying on silicon nanowire field-effect transistors for
      the detection of nerve agents. A fast, supersensitive and highly selective
      detection of organophosphorus molecules is reported. The results show also high
      selectivity in complex mixtures and on contaminated materials.

PMID- 21962682
TI  - Determination of nitroaromatic explosives in water samples by direct ultrasound
      assisted dispersive liquid-liquid microextraction followed by gas chromatography
      mass spectrometry.
AB  - A fast, simple, inexpensive, sensitive, efficient and environmental friendly
      direct ultrasound-assisted dispersive liquid-liquid microextraction (DUSA-DLLME)
      procedure has been developed to concentrate five nitroaromatic explosives from
      water samples prior to quantification by gas chromatography-mass spectrometry (GC
      MS). An efficient ultrasonic probe has been used to radiate directly the samples
      producing very fine emulsions from immiscible liquids. A D-optimal design was
      used for optimizing the factors and to evaluate their influential upon
      extraction. The optimum experimental conditions were: sample volume, 10 mL;
      extraction time, 60s; cycles, 0.6s(s(-1)); power of ultrasound energy, 40% (70
      W); and, extractant solvent (chlorobenzene) volume, 20 MUL. Under the optimized
      experimental conditions the method presents good level of repeatability with
      coefficients of variation under 6% (n=8; spiking level 10 MUg L(-1)). Calculated
      calibration curves gave high level of linearity with correlation coefficient
      values between 0.9949 and 0.9992. Limits of detection were ranged between 0.03
      and 0.91 MUg L(-1). Finally, the proposed method was applied to the analysis of
      two types of water samples, reservoir and effluent wastewater. The samples were
      previously analysed and confirmed free of target analytes. At 5 MUg L(-1) spiking
      level recovery values ranged between 75 and 96% for reservoir water sample
      showing that the matrix had a negligible effect upon extraction. However, a
      noticeable matrix effect (around 50% recovery) was observed for effluent
      wastewater sample. In order to alleviate this matrix effect, the standard
      addition calibration method was used for quantitative determination. This
      calibration method supplied recovery values ranged between 71 and 79%. The same
      conclusions have been obtained from an uncertainty budget evaluation study.

PMID- 21962683
TI  - Characterization of BSA unfolding and aggregation using a single-capillary
      viscometer and dynamic surface tension detector.
AB  - A dynamic surface tension detector (DSTD) has been equipped with an additional
      pressure sensor for simultaneous viscosity measurements, as a detector for flow
      injection analysis. The viscosity measurement is based on a single capillary
      viscometer (SCV) placed in parallel configuration with the DSTD. The viscometer
      in the optimized conditions consists of a PEEK capillary (i.d.=0.25 mm, L=75 cm)
      kept at constant temperature using a thermostatic bath, which leads on the two
      sides to the two arms of a differential piezoelectric pressure transducer with a
      range of 0-35 psi. The DSTD, described previously, measures the changing pressure
      across the liquid/air interface of 2 MUL drops repeatedly forming at the end of a
      capillary. SCV performance has been evaluated by measuring dynamic viscosity of
      water/glycerol mixtures analysed in flow injection and comparing the results with
      the values reported in the literature. The detection limits of SCV and DSTD,
      calculated as 3sigma of the blank, were 0.012 cP and 0.6 dyn cm(-1),
      respectively. The FI-SCV-DSTD system has been applied to the study of temperature
      induced denaturation/aggregation process in bovine serum albumin (BSA). The
      results have been supported and discussed with respect to BSA conformational
      analysis performed using Fourier Transform infrared spectroscopy.

PMID- 21962684
TI  - Chemical identification and determination of sulfonamides in n-component solid
      mixtures within THz-region--solid-state Raman spectroscopic and mass
      spectrometric study.
AB  - The identification and quantitative determination of sulfonamidesin solid-state
      as n-component mixtures is performed. The limits of detection (LODs), accuracy,
      precision and repeatability are obtained and discussed, using the Raman spectra
      within 200-30 cm(-1) region (6.00-0.9 THz). The excitations, corresponding to H
      bonding deformations, lattice vibrations, as well as coupling modes are used for
      determination. The validation of the statistical and mathematical tools for
      procedure of the spectroscopic patterns is performed. The possibilities of
      baseline correction methods, smoothing procedures, and non-linear curve fitting
      method for quantitative analysis within THz-region for complex spectroscopic
      patterns of n-component mixtures (n=1-5) are discussed. The hybrid HPLC tandem
      mass spectrometry (MS/MS) and powder XRD are applied as independent physical
      methods for analysis of the studied systems.

PMID- 21962685
TI  - Labelless impedance immunosensor based on polypyrrole-pyrolecarboxylic acid
      copolymer for hCG detection.
AB  - In this work, a sensitive label-free impedimetric hCG-immunosensor was
      constructed by using a commercial screen-printing carbon ink electrode (namely
      disposable electrochemical printed chip) as the basis. The carbon ink electrode
      of DEP chip is modified first by deposition of polypyrrole-pyrole-2-carboxylic
      acid copolymer and thence hCG antibody immobilization via the COOH groups of
      pyrrole-2-carboxylic acid, which can serve as a linker for covalent biomolecular
      immobilization. The experimental results exposed that the designed immunosensor
      is more sensitive than other previously reported immunosensors, in the case of
      detection limit and linear range for antigen detection. With optimal fabrication
      parameters, the detection limit for alpha-hCG was 2.3 pg/mL in 10mM phosphate
      buffer saline (PBS) solution containing 1% bovine serum albumine (BSA). Moreover,
      the use of inexpensive DEP chip as a basis for these immunosensors will allow for
      simple instrumentation, disposable and portable at low cost. This work also
      demonstrates a new approach to develop a sensitive and label-free impedimetric
      immunosensor based on screen-printed electrode for applications in clinical
      diagnosis.

PMID- 21962686
TI  - Determination of phenols in environmental water samples by two-step liquid-phase
      microextraction coupled with high performance liquid chromatography.
AB  - In this work, a two-step liquid-phase microextraction (LPME) method was presented
      for the extraction of phenols in environmental water samples. Firstly, the polar
      phenol in water samples (donor phase) was transferred to 1-octanol (extraction
      mesophase) by magnetic stirring-assisted LPME. Subsequently, target analytes in
      the 1-octanol was back extracted into 0.1 mol/L sodium hydroxide solution
      (acceptor phase) by vortex-assisted LPME. By combination of the two-step LPME,
      the enrichment factors were multiplied. The main features of this two-step LPME
      for phenols lie in the following aspects. Firstly, the extraction can be
      accomplished within relatively short time (ca. 20 min). Secondly, it was
      compatible with HPLC analysis, avoiding derivatization step that is generally
      necessary for GC analysis. Thirdly, high enrichment factors (296-954 fold) could
      be obtained for these analytes. Under the optimized conditions, the linearities
      were 10-1000, 1-500, 1-500, 5-500 and 1-500 ng/mL for different phenols with all
      regression coefficients higher than 0.9985. The limits of detection were in the
      range from 0.3 to 3.0 ng/mL for these analytes. Intra-and inter-day relative
      standard deviations were below 7.6%, indicating a good precision of the proposed
      method.

PMID- 21962687
TI  - Novel, simple and low-cost alternative method for fabrication of paper-based
      microfluidics by wax dipping.
AB  - Paper-based microfluidic devices are an alternative technology for fabricating
      simple, low-cost, portable and disposable platforms for clinical diagnosis.
      Hereby, a novel wax dipping method for fabricating paper-based microfluidic
      devices (MUPADs) is reported. The iron mould for wax dipping was created by a
      laser cutting technique. The designed pattern was transferred onto paper by
      dipping an assembly mould into melted wax. The optimal melting temperature and
      dipping time were investigated. The optimal melting temperature was in the range
      of 120-130 degrees C, and the optimal dipping time was 1s. The whole fabrication
      process could be finished within 1 min without the use of complicated instruments
      or organic solvents. The smallest hydrophilic channel that could be created by
      the wax dipping method was 639 +/- 7 MUm in size. The reproducibility of the
      MUPAD fabrication for hydrophilic channel width of the test zone and sample zone
      was 1.48% and 6.30%, respectively. To verify the performance of the MUPAD,
      multiple colorimetric assays for simultaneous detection of glucose and protein in
      real samples were performed. An enzymatic assay and the bromocresol green (BCG)
      method were conducted on the paper device to determine the presence of glucose
      and protein in a test solution. The results of the assays were not significantly
      different from those of the conventional methods (p>0.05, pair t-test and one-way
      ANOVA method). The wax dipping provides a new alternative method for fabricating
      lab-on-paper devices for multiple clinical diagnostics and will be very
      beneficial for developing countries.

PMID- 21962688
TI  - Voltammetric and amperometric determination of 2,4-dinitrophenol metabolites.
AB  - Methods for determination of 2-amino-4-nitrophenol and 4-amino-2-nitrophenol,
      metabolites of 2,4-dinitrophenol, were developed using differential pulse (DP)
      voltammetry and HPLC with amperometric and spectrophotometric detection. The
      applicability of these methods was tested by the determination of the analytes in
      model samples of urine after preliminary separation by solid-phase extraction.
      Voltammetry enabled parallel determination of both analytes, but its application
      in real matrix was severely limited due to the interference of other compounds
      present in urine. HPLC allowed the determination in real urine matrix down to
      micromolar concentrations; amperometric detection proved to be more sensitive and
      selective than the spectrophotometric one.

PMID- 21962689
TI  - Recovering incomplete data using Statistical Multiple Imputations (SMI): a case
      study in environmental chemistry.
AB  - This paper presents a statistical technique that can be applied to environmental
      chemistry data where missing values and limit of detection levels prevent the
      application of statistics. A working example is taken from an environmental
      leaching study that was set up to determine if there were significant differences
      in levels of leached arsenic (As), chromium (Cr) and copper (Cu) between
      lysimeters containing preservative treated wood waste and those containing
      untreated wood. Fourteen lysimeters were setup and left in natural conditions for
      21 weeks. The resultant leachate was analysed by ICP-OES to determine the As, Cr
      and Cu concentrations. However, due to the variation inherent in each lysimeter
      combined with the limits of detection offered by ICP-OES, the collected
      quantitative data was somewhat incomplete. Initial data analysis was hampered by
      the number of 'missing values' in the data. To recover the dataset, the
      statistical tool of Statistical Multiple Imputation (SMI) was applied, and the
      data was re-analysed successfully. It was demonstrated that using SMI did not
      affect the variance in the data, but facilitated analysis of the complete
      dataset.

PMID- 21962690
TI  - Optimisation of ICP-MS collision/reaction cell conditions for the determination
      of elements likely to be interfered (V, Cr, Fe, Co, Ni, As and Se) in foodstuffs.
AB  - A strategy for the accurate determination in foodstuffs of seven elements liable
      to be interfered with (V, Cr, Fe, Co, Ni, As and Se), was successfully applied.
      Firstly, to reduce spectroscopic interferences, four influential factors
      (hexapole and quadrupole bias, helium and hydrogen flows) of the
      collision/reaction cell device were optimised through the experimental design
      methodology. Secondly, non-spectroscopic interferences, which may severely
      disturb the analysis of matrices containing large amounts of non-target elements,
      were significantly reduced by a limited decrease in the flow rate of the optimum
      initial nebuliser rather than with a specific time-consuming dilution. Finally,
      the optimised multi-element method was subjected to a full validation that
      demonstrated its acceptable analytical performance.

PMID- 21962691
TI  - A novel microchip based on indium tin oxide coated glass for contactless
      conductivity detection.
AB  - A microfluidic chip manufactured from glass substrate and indium tin oxide (ITO)
      coated glass use for contactless conductivity detection was developed. The
      detecting electrodes were fabricated by screen-printing and chemical etching
      methods using an ITO-coated glass wafer. Then, the glass substrate containing
      separation channels was bonded with the bare side of the processed ITO-coated
      glass, thus producing an electrophoresis chip integrated with contactless
      conductivity detector. The prepared microchip displayed considerable stability
      and reproducibility. Sensitive response was obtained at optimal conditions
      (including the gap between electrodes, excitation frequency, and excitation
      voltage). The feasibility of this microfluidic device was examined by detection
      of inorganic ions, and further demonstrated by the quantification of aminopyrine
      and caffeine in a compound pharmaceutical. The two ingredients can be completely
      separated within 1 min. The detection limits were 8 MUg mL(-1) and 3 MUg mL(-1),
      respectively; with the correlation coefficient of 0.996-0.998 in the linear range
      from 10 MUg mL(-1) to 800 MUg mL(-1). The results have showed that the present
      method is sensitive, reliable and fast.

PMID- 21962692
TI  - A novel lable-free electrochemical immunosensor for carcinoembryonic antigen
      based on gold nanoparticles-thionine-reduced graphene oxide nanocomposite film
      modified glassy carbon electrode.
AB  - In this paper, gold nanoparticle-thionine-reduced graphene oxide (GNP-THi-GR)
      nanocomposites were prepared to design a label-free immunosensor for the
      sensitive detection of carcinoembryonic antigen (CEA). The nanocomposites with
      good biocompatibility, excellent redox electrochemical activity and large surface
      area were coated onto the glassy carbon electrode (GCE) surface and then CEA
      antibody (anti-CEA) was immobilized on the electrode to construct the
      immunosensor. The morphologies and electrochemistry of the formed nanocomposites
      were investigated by using scanning electron microscopy (SEM), ultraviolet
      visible (UV-vis) spectrometry, electrochemical impedance spectroscopy (EIS) and
      cyclic voltammetry (CV). CV and differential pulse voltammetry (DPV) studies
      demonstrated that the formation of antibody-antigen complexes decreased the peak
      current of THi in the GNP-THi-GR nanocomposites. The decreased currents were
      proportional to the CEA concentration in the range of 10-500 pg/mL with a
      detection limit of 4 pg/mL. The proposed method was simple, fast and inexpensive
      for the determination of CEA at very low levels.

PMID- 21962693
TI  - Effect of surface modification of indium tin oxide by nanoparticles on the
      electrochemical determination of tryptophan.
AB  - The effect of surface modification of indium tin oxide (ITO) by multi wall carbon
      nanotube (MWNT) and gold nanoparticles attached multi wall carbon nanotube (AuNP
      MWNT) has been studied to determine tryptophan, an important and essential amino
      acid for humans and herbivores. A detailed comparison has been made among the
      voltammetric response of bare ITO, MWNT/ITO and AuNP-MWNT/ITO in respects of
      several essential analytical parameters viz. sensitivity, detection limit, peak
      current and peak potential of tryptophan. The AuNP-MWNT/ITO exhibited a well
      defined anodic peak at pH 7.2 at a potential of ~ 669 mV for the oxidation of
      tryptophan as compared to 760 mV at MWNT/ITO electrode. Under optimum conditions
      linear calibration curve was obtained over tryptophan concentration range 0.5
      90.0 MUM in phosphate buffer solution of pH 7.2 with detection limit and
      sensitivity of 0.025 MUM and 0.12 MUA MUM(-1), respectively. The oxidation of
      tryptophan occurred in a pH dependent, 2e(-) and 2H(+) process and the electrode
      reaction followed adsorption controlled pathway. The method has been found
      selective and successfully implemented for the determination of tryptophan in
      human urine and plasma samples using standard addition method. The electrode
      exhibited an efficient catalytic response with good reproducibility and
      stability.

PMID- 21962694
TI  - Determination of formaldehyde in beverages using microwave-assisted
      derivatization and ionic liquid-based dispersive liquid-liquid microextraction
      followed by high-performance liquid chromatography.
AB  - A simple method based on simultaneous microwave-assisted derivatization and ionic
      liquid-based dispersive liquid-liquid microextraction (IL-based DLLME) is
      proposed for the derivatization, extraction and preconcentration of formaldehyde
      in beverage samples prior to the determination by high-performance liquid
      chromatography (HPLC). Formaldehyde was in situ derivatized with 2,4
      dinitrophenylhydrazine (DNPH) and simultaneously extracted and preconcentrated by
      using microwave-assisted derivatization and IL-based DLLME in a single step.
      Several experimental parameters, including type and volume of extraction solvent,
      type and volume of disperser, microwave power and irradiation time, volume of
      DNPH, pH of sample solution, and ionic strength were evaluated. When the
      microwave power was 120 W, formaldehyde could be derivatized and extracted
      simultaneously only within 90 s. Under optimal experimental conditions, good
      linearity was observed in the range of 0.5-50 ng/mL with the correlation
      coefficient of 0.9965, and the limit of detection was 0.12 ng/mL. The proposed
      method was applied to the analysis of different beverage samples, and the
      recoveries of formaldehyde obtained were in the range of 84.9-95.1% with the
      relative standard deviations lower than 8.4%. The results showed that the
      proposed method was a rapid, convenient and feasible method for the determination
      of formaldehyde in beverage samples.

PMID- 21962695
TI  - (-)-Epigallocatechin gallate inhibits hepatitis C virus (HCV) viral protein NS5B.
AB  - In this study, we elucidated a small molecule inhibitor on viral protein NS5B
      identified through a high-throughput screening strategy using optical
      nanoparticle-based RNA oligonucleotide. We have previously shown that quantum
      dots (QDs)-RNA oligonucleotide can specifically recognize the HCV viral proteins.
      We have also demonstrated that conjugated QDs-RNA oligonucleotide can
      specifically and sensitively interact with designed biochips [1,2]. Among the
      flavonoids examined, (-)-epigallocatechin gallate (EGCG) demonstrated a
      remarkable inhibition activity on HCV viral protein, NS5B. (-)-Epigallocatechin
      gallate, at 0.005 MUg mL(-1) or more, concentration-dependently attenuated the
      binding affinity on a designed biochip as evidenced by QDs-RNA oligonucleotide.
      At a concentration of 0.1 MUg mL(-1), (-)-epigallocatechin gallate showed a 50%
      inhibition activity on QDs-RNA oligonucleotide biochip assay. We screened a small
      molecule inhibitor on the viral protein, NS5B, identified through a high
      throughput screening strategy using on-chip optical nanoparticle-based RNA
      oligonucleotide on chip. In this designed strategy, the convenient and efficient
      screening and development of an on-chip viral protein inhibitor using a QDs-RNA
      oligonucleotide assay is achievable with high sensitivity and simplicity. In
      addition, this platform is expected to be applicable toward the inhibitor
      screening of other types of diseases.

PMID- 21962696
TI  - Detection of glucose in synthetic tear fluid using dually functionalized gold
      nanoparticles.
AB  - A simple fluorescent sensing of glucose in aqueous fluids (e.g. tear fluid) using
      dually functionalized gold nanoparticles is presented. As a first step gold
      nanoparticles (AuNPs) were synthesized using oxidised dextran which acted both as
      reducing and stabilizing agent. Aminophenyl boronic acid was conjugated onto
      AuNPs by Schiff's base formation and the formed Schiff's base was stabilized by
      sodium borohydride reduction. Rhodamine B isothiocyanate (RBITC) was then
      assembled onto the modified AuNPs. The fluorescence of RBITC was nearly quenched
      and found to be revived when glucose was added. It is reasoned that the glucose
      binding induces restructuring of the surface assembly resulting in an overall
      increase in the size and thereby enhancing the distance between the gold core and
      fluorophore. TEM image and size measurements using dynamic light scattering (DLS)
      in fact, reflected this possibility. The increase in fluorescence was
      proportional with the concentration of glucose enabling quantitative detection. A
      good linearity was observed between the fluorescence intensity and glucose
      concentration in a range of 0.025-0.125 MUM with detection limit of 0.005 +/-
      0.002 MUM. The potential of the method was demonstrated by measuring glucose in
      real tear fluids collected from volunteers. The method is extremely sensitive and
      can be employed to measure low concentration of glucose in aqueous fluids such as
      tear.

PMID- 21962697
TI  - Quantum dot-enhanced chemiluminescence detection for simultaneous determination
      of dopamine and epinephrine by capillary electrophoresis.
AB  - A sensitive method based on quantum dot (QD)-enhanced capillary electrophoresis
      chemiluminescence (CE-CL) detection was developed for simultaneous determination
      of dopamine (DA) and epinephrine (E). In this work, CdTe QD was added into the
      running buffer of CE to catalyze the post-column CL reaction between luminol and
      hydrogen peroxide, achieving higher CL emission. Negative peaks were produced due
      to the inhibitory effects on CL emission from DA and E eluted from the
      electrophoretic capillary. The decrease in CL intensity was proportional to the
      concentration of DA and E in the range of 8.0 * 10(-8)-5.0 * 10(-6)M and 4.0 *
      10(-8)-5.0 * 10(-6)M, respectively. Detection limits for DA and E were 2.3 * 10(
      8)M and 9.3 * 10(-9)M, respectively. Using this method, the levels of DA and E in
      human urine from healthy donors were determined.

PMID- 21962698
TI  - Determination of silica coating efficiency on metal particles using multiple
      digestion methods.
AB  - Nano-sized metal particles, including both elemental and oxidized metals, have
      received significant interest due to their biotoxicity and presence in a wide
      range of industrial systems. A novel silica technology has been recently explored
      to minimize the biotoxicity of metal particles by encapsulating them with an
      amorphous silica shell. In this study, a method to determine silica coating
      efficiency on metal particles was developed. Metal particles with silica coating
      were generated using gas metal arc welding (GMAW) process with a silica precursor
      tetramethylsilane (TMS) added to the shielding gas. Microwave digestion and
      Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES) were employed
      to solubilize the metal content in the particles and analyze the concentration,
      respectively. Three acid mixtures were tested to acquire the appropriate
      digestion method targeting at metals and silica coating. Metal recovery
      efficiencies of different digestion methods were compared through analysis of
      spiked samples. HNO(3)/HF mixture was found to be a more aggressive digestion
      method for metal particles with silica coating. Aqua regia was able to
      effectively dissolve metal particles not trapped in the silica shell. Silica
      coating efficiencies were thus calculated based on the measured concentrations
      following digestion by HNO(3)/HF mixture and aqua regia. The results showed 14
      39% of welding fume particles were encapsulated in silica coating under various
      conditions. This newly developed method could also be used to examine the silica
      coverage on particles of silica shell/metal core structure in other
      nanotechnology areas.

PMID- 21962699
TI  - A practical method for the determination of sulphur in coal samples by high
      resolution continuum source flame atomic absorption spectrometry.
AB  - Sulphur in coal was determined using a high-resolution continuum source flame
      atomic absorption spectrophotometer (HR-CS-FAAS) with actylene/air flame. The C-S
      absorption band at 258.056 nm was found the most suitable analytical line with
      respect to sensitivity and spectral interferences. The instrumental parameters
      were optimized. The coal samples were dried and dissolved using microwave
      assisted digestion technique. The validity of the method was tested using
      standard reference material and certified values were found in the limits of 95%
      confidence level. Since the concentrations of matrix elements of coal other than
      carbon are low enough not to cause any spectral interferences, the linear
      calibration method was applied in all quantifications without any problem. The
      calibration standards were prepared in sulphuric acid. The method was accurate,
      fast, simple and sensitive. The limit of detection (LOD, 3delta, N=10) and the
      limit of quantification (LOQ, 10delta, N=10) were found to be 0.01 and 0.03%
      (w/w), respectively. The sulphur concentrations of various kinds of the coal
      samples received around Turkey were determined. The sulphur contents of the coal
      samples were ranged from <= LOQ to 1.2%.

PMID- 21962700
TI  - Preparation of a strong-cation exchange monolith by a novel method and its
      application in the separation of IgG on high performance liquid chromatography.
AB  - A strong cation-exchange poly(vinyl carboxylate-co-ethyleneglycol dimethacrylate)
      (poly(VC-co-EDMA)) monolithic column for high performance liquid chromatography
      (HPLC) has been prepared firstly by atom transfer radical polymerization (ATRP)
      without the expensive complexing ligand, in which vinyl carboxylate was used as
      the monomer, ethyleneglycol dimethacrylate as the cross linking agent, carbon
      tetrachloride as the initiator and ferrous chloride as the catalyst. Conditions
      of the polymerization have been studied and optimized. Morphology of monolithic
      materials was studied by scanning electronic microscopy. Chemical groups of the
      monolith were assayed by infrared spectra method and the pore size distribution
      was determined by a mercury porosimeter. Moreover, the monolith was modified to
      bear strong-cation exchange groups and tested on the separation of human immune
      globulin G (IgG) from human plasma in conjunction with HPLC. Good resolution was
      obtained in a short time (10 min) in the separation. The effects of pH and buffer
      concentration on the elution of IgG have been investigated. Moreover, frontal
      analytical method was used to get the IgG dynamic banding capacity of the
      monolith that was 3.0 mg g(-1). Besides, the monolith was also used to separate
      lysozyme from egg white and separate the mixture of papain, snailase and IgG.

PMID- 21962701
TI  - Color response of tri-armed azo host colorimetric sensors and test kit for
      fluoride.
AB  - Five new chromogenic tripodal receptors (2a-e) containing electron withdrawing
      and donating groups appended to the azophenol moiety were synthesized,
      characterized, and their chromogenic behaviors toward various anions were
      investigated. These tripodal receptors showed a distinct color change only when
      treated with fluoride ions in CH(3)CN solution. Yet, other anions such as Cl(-),
      Br(-), I(-), NO(3)(-), ClO(4)(-), AcO(-), HSO(4)(-), and H(2)PO(4)(-) could not
      cause any color change. Thus, the receptors 2a-e can be used as a colorimetric
      chemosensor for the determination of fluoride ion. In addition, (1)H NMR
      experiments were carried out to explore the nature of interaction between
      tripodal receptors and fluoride. Finally, analytical application and the use of
      test strip of the receptor 2b to detect fluoride was also reported.

PMID- 21962702
TI  - Determination of fluorine in tea using high-resolution molecular absorption
      spectrometry with electrothermal vaporization of the calcium mono-fluoride CaF.
AB  - High-resolution continuum source molecular absorption of the calcium mono
      fluoride molecule CaF in a graphite furnace has been used to determine fluorine
      in tea after acid digestion, alkaline solubilization and preparation of a
      conventional aqueous infusion. The strongest absorption 'line' of the CaF
      molecule is at 606.440 nm, which is part of the rotational fine structure of the
      X(2)Sigma(+)-A(2)Pi electronic transition; it has a bond dissociation energy of
      529 kJ mol(-1), which is comparable with other molecules used for fluorine
      determination. One advantage of using Ca as the molecule-forming reagent is that
      spectral interferences are extremely unlikely in the spectral range of its
      strongest absorption. Another advantage is that Ca acts both as molecule forming
      reagent and chemical modifier, so that no other reagent has to be added, making
      the method very simple. The only disadvantage is that Ca has a somewhat negative
      influence on the graphite tube lifetime. The limit of detection was found to be
      0.16 mg L(-1) F, corresponding to 1.6 ng F absolute, and the calibration curve
      was linear in the range between 0.5 and 25 mg L(-1) with a correlation
      coefficient of R=0.9994. The results obtained for a certified tea reference
      material were in agreement with the certified value on a 95% confidence level.
      There was also no difference between the results obtained after an acid digestion
      and an alkaline solubilization for 10 tea samples, based on a paired t-test. The
      values found in the 10 samples ranged between 42 MUg g(-1) and 87 MUg g(-1) F;
      the tea infusions contained between 21 MUg g(-1) and 56 MUg g(-1) F, with an
      extraction rate between 48% and 74%.

PMID- 21962703
TI  - Quantitative and qualitative prediction of corneal permeability for drug-like
      compounds.
AB  - A set of 69 drug-like compounds with corneal permeability was studied using
      quantitative and qualitative modeling techniques. Multiple linear regression
      (MLR) and multilayer perceptron neural network (MLP-NN) were used to develop
      quantitative relationships between the corneal permeability and seven molecular
      descriptors selected by stepwise MLR and sensitivity analysis methods. In order
      to evaluate the models, a leave many out cross-validation test was performed,
      which produced the statistic Q(2)=0.584 and SPRESS=0.378 for MLR and Q(2)=0.774
      and SPRESS=0.087 for MLP-NN. The obtained results revealed the suitability of MLP
      NN for the prediction of corneal permeability. The contribution of each
      descriptor to MLP-NN model was evaluated. It indicated the importance of the
      molecular volume and weight. The pattern recognition methods principal component
      analysis (PCA) and hierarchical clustering analysis (HCA) have been employed in
      order to investigate the possible qualitative relationships between the molecular
      descriptors and the corneal permeability. The PCA and HCA results showed that,
      the data set contains two groups. Then, the same descriptors used in quantitative
      modeling were considered as inputs of counter propagation neural network (CPNN)
      to classify the compounds into low permeable (LP) and very low permeable (VLP)
      categories in supervised manner. The overall classification non error rate was
      95.7% and 95.4% for the training and prediction test sets, respectively. The
      results revealed the ability of CPNN to correctly recognize the compounds
      belonging to the categories. The proposed models can be successfully used to
      predict the corneal permeability values and to classify the compounds into LP and
      VLP ones.

PMID- 21962704
TI  - Facile synthesis of fluorescent Au@SiO2 nanocomposites for application in
      cellular imaging.
AB  - A novel fluorescent Au@SiO(2) nanocomposite, with average size of ca. 30 nm in
      the diameter, was prepared via a simple microemulsion method. Additionally,
      transmission electron microscopy (TEM), UV-Vis absorption spectra, Fourier
      transform infrared (FT-IR) spectra and fluorescence spectra were used to
      characterize this nanocomposite. This newly synthesized, silica-wrapped, gold
      nanocluster has the following advantages: good water solubility, exceptional
      biocompatibility, favorable surface properties and excellent fluorescence
      properties. Because of these advantages, a Au@SiO(2) nanocomposite is
      exceptionally suitable for biological applications. In this study, cellular
      imaging, as a form of biological application, has been fully investigated, and it
      was discovered, after covalent conjugation of folic acid (FA), that the
      nanocomposite effectively recognized over expressed folic acid receptors (FARs)
      on the HeLa cell's surface. Therefore, this fluorescent Au@SiO(2) nanocomposite
      could be used as a new fluorescent probe for selective biological imaging.

PMID- 21962705
TI  - Stripping voltammetric determination of mercury(II) at antimony-coated carbon
      paste electrode.
AB  - A new procedure was elaborated to determine mercury(II) using an anodic stripping
      square-wave voltammetry at the antimony film carbon paste electrode (SbF-CPE). In
      highly acidic medium of 1M hydrochloric acid, voltammetric measurements can be
      realized in a wide potential window. Presence of cadmium(II) allows to separate
      peaks of Hg(II) and Sb(III) and apparently catalyses reoxidation of
      electrolytically accumulated mercury, thus allowing its determination at ppb
      levels. Calibration dependence was linear up to 100 ppb Hg with a detection limit
      of 1.3 ppb. Applicability of the method was tested on the real river water
      sample.

PMID- 21962706
TI  - Peculiarities of a novel bioenzymatic reactor using carbon nanotubes as enzyme
      activity enhancers: application to arginase.
AB  - Multiwalled carbon nanotubes have been entrapped in a porous monolithic
      chromatographic support. This support was used for the covalent immobilization of
      the arginase enzyme a novel target in hypertension. The effect of the nanotube
      (NT) amount into the monolith was analyzed. The obtained results demonstrated the
      ability of carbon nanotubes to increase significantly the performance of this
      novel bioactive support.

PMID- 21962707
TI  - Influence of microwave heating on fluoride, chloride, nitrate and sulfate
      concentrations in water.
AB  - This paper describes a study about the influence of microwave radiation using
      closed vessels on fluoride, chloride, nitrate and sulfate concentrations in
      aqueous media. The experiments were processed by heating water using PFA vessels
      and a microwave cavity oven, determining the anions by ion chromatography. The
      influence of the exposure time, the atmospheric composition, the kind of heating
      (water bath or microwave radiation) and the possible formation of hydrogen
      peroxide were investigated. The limits of quantification for fluoride, chloride,
      nitrate and sulfate were respectively of 0.17, 0.15, 0.55 and 0.57 MUg L(-1), and
      precision, expressed as RSD, was <4% for all considered anions. The hydrogen
      peroxide was quantified by spectrophotometry, and the limit of quantification and
      precision were 24 MUg L(-1) and <5% (n=10), respectively. The results demonstrate
      a significant increase in the anion concentration levels (between 63 and 89%)
      when microwave heating was used in comparison with heating by water bath. In
      addition, these changes observed can be mainly attributed to the species
      transfers, either between gaseous (atmospheric gases) and liquid (water) phases
      for nitrate, or between vessels walls and water for fluoride, chloride and
      sulfate. Additionally, hydrogen peroxide concentration higher than 45 MUg L(-1)
      was determined when water was exposed to microwave radiation.

PMID- 21962708
TI  - Hydrogen peroxide-sodium hydrosulfite chemiluminescence system combined with high
      performance liquid chromatography for determination of 1-hydroxypyrene in
      airborne particulates.
AB  - In this research, a highly sensitive chemiluminescence method based on a sodium
      hydrosulfite (NaHSO(3))-hydrogen peroxide (H(2)O(2)) reaction for the
      determination of 1-hydroxypyrene (1-OHP) was developed. The response of this
      system was linear in the range from 0.5 to 50 pmol (R(2)=0.9983). The limit of
      detection for 1-OHP was 100 fmol (S/N=3). 1-OHP in airborne particulates was well
      separated from interfering compounds using an ODS column with 75% methanol as the
      mobile phase in isocratic mode. The proposed method was successfully applied to
      determine the 1-OHP in airborne particulates collected in Kanazawa, Japan. The
      average concentration of 1-OHP in the atmosphere was 2.0 pg/m(3) (9.2 fmol/m(3)).

PMID- 21962709
TI  - Decoding successive computational stages of saliency processing.
AB  - An important requirement for vision is to identify interesting and relevant
      regions of the environment for further processing. Some models assume that
      salient locations from a visual scene are encoded in a dedicated spatial saliency
      map [1, 2]. Then, a winner-take-all (WTA) mechanism [1, 2] is often believed to
      threshold the graded saliency representation and identify the most salient
      position in the visual field. Here we aimed to assess whether neural
      representations of graded saliency and the subsequent WTA mechanism can be
      dissociated. We presented images of natural scenes while subjects were in a
      scanner performing a demanding fixation task, and thus their attention was
      directed away. Signals in early visual cortex and posterior intraparietal sulcus
      (IPS) correlated with graded saliency as defined by a computational saliency
      model. Multivariate pattern classification [3, 4] revealed that the most salient
      position in the visual field was encoded in anterior IPS and frontal eye fields
      (FEF), thus reflecting a potential WTA stage. Our results thus confirm that
      graded saliency and WTA-thresholded saliency are encoded in distinct neural
      structures. This could provide the neural representation required for rapid and
      automatic orientation toward salient events in natural environments.

PMID- 21962710
TI  - An EDMD mutation in C. elegans lamin blocks muscle-specific gene relocation and
      compromises muscle integrity.
AB  - BACKGROUND: In worms, as in other organisms, many tissue-specific promoters are
      sequestered at the nuclear periphery when repressed and shift inward when
      activated. It has remained unresolved, however, whether the association of
      facultative heterochromatin with the nuclear periphery, or its release, has
      functional relevance for cell or tissue integrity. RESULTS: Using ablation of the
      unique lamin gene in C. elegans, we show that lamin is necessary for the
      perinuclear positioning of heterochromatin. We then express at low levels in
      otherwise wild-type worms a lamin carrying a point mutation, Y59C, which in
      humans is linked to an autosomal-dominant form of Emery-Dreifuss muscular
      dystrophy. Using embryos and differentiated tissues, we track the subnuclear
      position of integrated heterochromatic arrays and their expression. In LMN-1 Y59C
      expressing worms, we see abnormal retention at the nuclear envelope of a gene
      array bearing a muscle-specific promoter. This correlates with impaired
      activation of the array-borne myo-3 promoter and altered expression of a number
      of muscle-specific genes. However, an equivalent array carrying the intestine
      specific pha-4 promoter is expressed normally and shifts inward when activated in
      gut cells of LMN-1 Y59C worms. Remarkably, adult LMN-1 Y59C animals have
      selectively perturbed body muscle ultrastructure and reduced muscle function.
      CONCLUSION: Lamin helps sequester heterochromatin at the nuclear envelope, and
      wild-type lamin permits promoter release following tissue-specific activation. A
      disease-linked point mutation in lamin impairs muscle-specific reorganization of
      a heterochromatic array during tissue-specific promoter activation in a dominant
      manner. This dominance and the correlated muscle dysfunction in LMN-1 Y59C worms
      phenocopies Emery-Dreifuss muscular dystrophy.

PMID- 21962711
TI  - Multiple TGF-beta superfamily signals modulate the adult Drosophila immune
      response.
AB  - TGF-beta superfamily signals play complex roles in regulation of tissue repair
      and inflammation in mammals [1]. Drosophila melanogaster is a well-established
      model for the study of innate immune function [2, 3] and wound healing [4-7].
      Here, we explore the role and regulation of two TGF-beta superfamily members,
      dawdle and decapentaplegic (dpp), in response to wounding and infection in adult
      Drosophila. We find that both TGF-beta signals exhibit complex regulation in
      response to wounding and infection, each is expressed in a subset of phagocytes,
      and each inhibits a specific arm of the immune response. dpp is rapidly activated
      by wounds and represses the production of antimicrobial peptides; flies lacking
      dpp function display persistent, strong antimicrobial peptide expression after
      even a small wound. dawdle, in contrast, is activated by Gram-positive bacterial
      infection but repressed by Gram-negative infection or wounding; its role is to
      limit infection-induced melanization. Flies lacking dawdle function exhibit
      melanization even when uninfected. Together, these data imply a model in which
      the bone morphogenetic protein (BMP) dpp is an important inhibitor of
      inflammation following sterile injury whereas the activin-like dawdle determines
      the nature of the induced immune response.

PMID- 21962712
TI  - Single-unit responses selective for whole faces in the human amygdala.
AB  - The human amygdala is critical for social cognition from faces, as borne out by
      impairments in recognizing facial emotion following amygdala lesions [1] and
      differential activation of the amygdala by faces [2-5]. Single-unit recordings in
      the primate amygdala have documented responses selective for faces, their
      identity, or emotional expression [6, 7], yet how the amygdala represents face
      information remains unknown. Does it encode specific features of faces that are
      particularly critical for recognizing emotions (such as the eyes), or does it
      encode the whole face, a level of representation that might be the proximal
      substrate for subsequent social cognition? We investigated this question by
      recording from over 200 single neurons in the amygdalae of seven neurosurgical
      patients with implanted depth electrodes [8]. We found that approximately half of
      all neurons responded to faces or parts of faces. Approximately 20% of all
      neurons responded selectively only to the whole face. Although responding most to
      whole faces, these neurons paradoxically responded more when only a small part of
      the face was shown compared to when almost the entire face was shown. We suggest
      that the human amygdala plays a predominant role in representing global
      information about faces, possibly achieved through inhibition between individual
      facial features.

PMID- 21962713
TI  - Mobile 24 nt small RNAs direct transcriptional gene silencing in the root
      meristems of Arabidopsis thaliana.
AB  - RNA silencing in flowering plants generates a signal that moves between cells and
      through the phloem [1, 2]. Nucleotide sequence specificity of the signal is
      conferred by 21, 22, and 24 nucleotide (nt) sRNAs that are generated by Dicer
      like (DCL) proteins [3]. In the recipient cells these sRNAs bind to Argonaute
      (AGO) effectors of silencing and the 21 nt sRNAs mediate posttranscriptional
      regulation (PTGS) via mRNA cleavage [4] whereas the 24 nt sRNAs are associated
      with RNA-dependent DNA methylation (RdDM) [5] that may underlie transcriptional
      gene silencing (TGS). Intriguingly, genes involved in TGS are required for graft
      transmissible gene silencing associated with PTGS [6]. However, some of the same
      genes were also required for spread of a PTGS silencing signal out of the veins
      of Arabidopsis [7], and grafting tests failed to demonstrate direct transmission
      of TGS signals [8-10]. It seemed likely, therefore, that mobile silencing is
      associated only with PTGS. To address this possibility, we grafted TGS-inducing
      wild-type Arabidopsis and a mutant that is compromised in 24 nt sRNA production
      onto a wild-type reporter line. The 21-24 nt sRNAs from the TGS construct were
      transmitted across a graft union but only the 24 nt sRNAs directed RdDM and TGS
      of a transgene promoter in meristematic cells. These data extend the significance
      of an RNA silencing signal to embrace epigenetics and transcriptional gene
      silencing and support the hypothesis that these signals transmit information to
      meristematic cells where they initiate persistent epigenetic changes that may
      influence growth, development, and heritable phenotypes.

PMID- 21962714
TI  - Practicing coarse orientation discrimination improves orientation signals in
      macaque cortical area v4.
AB  - Practice improves the performance in visual tasks, but mechanisms underlying this
      adult brain plasticity are unclear. Single-cell studies reported no [1], weak
      [2], or moderate [3, 4] perceptual learning-related changes in macaque visual
      areas V1 and V4, whereas none were found in middle temporal (MT) [5]. These
      conflicting results and modeling of human (e.g., [6, 7]) and monkey data [8]
      suggested that changes in the readout of visual cortical signals underlie
      perceptual learning, rather than changes in these signals. In the V4 learning
      studies, monkeys discriminated small differences in orientation, whereas in the
      MT study, the animals discriminated opponent motion directions. Analogous to the
      latter study, we trained monkeys to discriminate static orthogonal orientations
      masked by noise. V4 neurons showed robust increases in their capacity to
      discriminate the trained orientations during the course of the training. This
      effect was observed during discrimination and passive fixation but specifically
      for the trained orientations. The improvement in neural discrimination was due to
      decreased response variability and an increase of the difference between the mean
      responses for the two trained orientations. These findings demonstrate that
      perceptual learning in a coarse discrimination task indeed can change the
      response properties of a cortical sensory area.

PMID- 21962716
TI  - Parallel processing of appetitive short- and long-term memories in Drosophila.
AB  - It is broadly accepted that long-term memory (LTM) is formed sequentially after
      learning and short-term memory (STM) formation, but the nature of the
      relationship between early and late memory traces remains heavily debated [1-5].
      To shed light on this issue, we used an olfactory appetitive conditioning in
      Drosophila, wherein starved flies learned to associate an odor with the presence
      of sugar [6]. We took advantage of the fact that both STM and LTM are generated
      after a unique conditioning cycle [7, 8] to demonstrate that appetitive LTM is
      able to form independently of STM. More specifically, we show that (1) STM
      retrieval involves output from gamma neurons of the mushroom body (MB), i.e., the
      olfactory memory center [9, 10], whereas LTM retrieval involves output from
      alphabeta MB neurons; (2) STM information is not transferred from gamma neurons
      to alphabeta neurons for LTM formation; and (3) the adenylyl cyclase RUT, which
      is thought to operate as a coincidence detector between the olfactory stimulus
      and the sugar stimulus [11-14], is required independently in gamma neurons to
      form appetitive STM and in alphabeta neurons to form LTM. Taken together, these
      results demonstrate that appetitive short- and long-term memories are formed and
      processed in parallel.

PMID- 21962715
TI  - Cohesin selectively binds and regulates genes with paused RNA polymerase.
AB  - BACKGROUND: The cohesin complex mediates sister chromatid cohesion and regulates
      gene transcription. Prior studies show that cohesin preferentially binds and
      regulates genes that control growth and differentiation and that even mild
      disruption of cohesin function alters development. Here we investigate how
      cohesin specifically recognizes and regulates genes that control development in
      Drosophila. RESULTS: Genome-wide analyses show that cohesin selectively binds
      genes in which RNA polymerase II (Pol II) pauses just downstream of the
      transcription start site. These genes often have GAGA factor (GAF) binding sites
      100 base pairs (bp) upstream of the start site, and GT dinucleotide repeats 50 to
      800 bp downstream in the plus strand. They have low levels of histone H3 lysine
      36 trimethylation (H3K36me3) associated with transcriptional elongation, even
      when highly transcribed. Cohesin depletion does not reduce polymerase pausing, in
      contrast to depletion of the NELF (negative elongation factor) pausing complex.
      Cohesin, NELF, and Spt5 pausing and elongation factor knockdown experiments
      indicate that cohesin does not inhibit binding of polymerase to promoters or
      physically block transcriptional elongation, but at genes that it strongly
      represses, it hinders transition of paused polymerase to elongation at a step
      distinct from those controlled by Spt5 and NELF. CONCLUSIONS: Our findings argue
      that cohesin and pausing factors are recruited independently to the same genes,
      perhaps by GAF and the GT repeats, and that their combined action determines the
      level of actively elongating RNA polymerase.

PMID- 21962717
TI  - Antihypertensive drugs and the risk of prostate cancer.

PMID- 21962718
TI  - Clinical and genetic characteristics in patients with Huntington's Disease from
      Argentina.
AB  - Huntington's Disease (HD) is a neurodegenerative disease, caused by the expansion
      of an unstable (CAG)(n) in the HTT gene. There is scarce data about the disease
      in Argentina. OBJECTIVE: To describe the demographic, clinical and molecular data
      in patients with HD from Argentina. PATIENTS AND METHODS: 59 HD patients were
      recruited at our department. Comprehensive interviews, neurological examination
      and genetic analysis were performed in probands. Statistical analysis was
      conducted using G-Stat 2.0 and non-parametric tests (Wilcoxon). RESULTS: 32 women
      and 27 men were diagnosed with a mean age of 45.7 +/- 16.2 years and a mean age
      at onset of 35.8 +/- 14.8 years. We found no gender prevalence and an inverse
      correlation between size of mutant CAG repeat sequence and age at onset, r = 
      0.58, r(2) = 33.6, Pearson's correlation coefficient p = 0.0008. Juvenile HD in
      this series of patients was higher than previously reported (16.6% vs. <10%). The
      mean CAG repeat in the expanded allele was 45.1. The number of CAG repeats in
      Argentinean controls was 17.8, which is similar to the literature of the European
      population. CONCLUSIONS: This is the first series of Argentinean HD patients with
      demographic, clinical and molecular data. Our findings appear similar to the ones
      described in Western European populations.

PMID- 21962719
TI  - Recognizing dangerous snakes in the United States and Canada: a novel 3-step
      identification method.
AB  - The rapid and accurate recognition of dangerously venomous snakes following bites
      is crucial to making appropriate decisions regarding first aid, evacuation, and
      treatment. Past recommendations for identification of dangerous North American
      pit vipers have often required subjective determinations of head shape or relied
      on traits shared with some nondangerous species (elliptical pupils and undivided
      subcaudal scales). Heat-sensitive facial pits are diagnostic but require close
      examination of the dangerous head, and cephalic traits are useless when working
      with a decapitated carcass. Exclusive of cephalic traits, pit vipers north of
      Mexico can be recognized by the combination of keeled middorsal scales and
      undivided subcaudal scales. The order of colored rings is usually suggested to
      identify coral snakes in the United States, yet extension of the colored rings
      across the ventral scales must be added as an essential identifying factor to
      ensure elimination of all harmless look-alikes. A novel 3-step flow chart is
      presented that allows dangerous snakes in the United States and Canada to be
      recognized quickly and dependably without relying on cephalic traits. This
      process cannot be used in other countries, however, due to greater variability of
      these characteristics in snakes from other parts of the world. Finally, close
      examination of potentially venomous snakes is extraordinarily dangerous and steps
      to safeguard those making such observations are discussed.

PMID- 21962720
TI  - Phantoms in the mortuary--DNA transfer during autopsies.
AB  - DNA evidence frequently plays an important role in criminal investigations and in
      some cases may be the only means of convicting a suspect. The constant
      improvement of DNA analysis techniques affords the individualization of minute
      amounts of DNA, aggravating the risk of contamination artifacts. In our study, we
      investigated the prevalence of DNA contamination in the autopsy facilities of the
      Institutes of Legal Medicine in Essen and Kiel (Germany). Using DNA-free swabs,
      we took samples from instruments used during autopsy and autopsy tables. Surfaces
      and instruments were routinely cleaned before sampling. Swabs were subjected to
      different PCRs to quantify the total amount of DNA and to amplify individual
      specific STR-markers. In most samples, alleles that could be linked to bodies
      that had been autopsied before were found. Furthermore, we could show that a DNA
      transfer from the autopsy table to a body was detectable in four out of six cases
      investigated. The interpretation of DNA typing results may thus be severely
      complicated. To avoid DNA contamination, we tried out different cleaning methods,
      of which only a bleach containing cleaner showed sufficient results.

PMID- 21962721
TI  - Exposure to an urban environment alters the local bias of a remote culture.
AB  - There is substantial evidence that populations in the Western world exhibit a
      local bias compared to East Asian populations that is widely ascribed to a
      difference between individualistic and collectivist societies. However, we report
      that traditional Himba - a remote interdependent society - exhibit a strong local
      bias compared to both Japanese and British participants in the Ebbinghaus
      illusion and in a similarity-matching task with hierarchical figures. Critically,
      we measured the effect of exposure to an urban environment on local bias in the
      Himba. Even a brief exposure to an urban environment caused a shift in processing
      style: the local bias was reduced in traditional Himba who had visited a local
      town and even more reduced in urbanised Himba who had moved to that town on a
      permanent basis. We therefore propose that exposure to an urban environment
      contributes to the global bias found in Western and Japanese populations.

PMID- 21962722
TI  - Prevention of venous thromboembolism in patients with cancer: guidelines of the
      Italian Society for Haemostasis and Thrombosis (SISET)(1).
AB  - BACKGROUND: Prevention of venous thromboembolism (VTE) in cancer patients remains
      controversial in most clinical settings. PURPOSE: The Italian Society for
      Haemostasis and Thrombosis (SISET) commissioned a project to develop clinical
      practice guidelines for the prevention of VTE in patients with malignancy.
      METHODS: Key questions concerning the prevention of VTE in patients with
      malignancy were formulated by a multidisciplinary working group consisting of
      experts in clinical medicine and research. After a systematic review and
      discussion of the literature, recommendations were formulated and graded
      according to the supporting evidence. For those questions for which the
      literature search did not find any definitive answers (due to absence of
      evidence, low quality evidence and/or contradictory evidence), a formal consensus
      method was used instead to issue clinical recommendations. RESULTS: The search
      for "VTE prevention" resulted in 1021 citations; 69 articles were selected and 24
      were used for drafting clinical recommendations. Four areas were graded A to C:
      1) Need of prevention (pharmacological and/or mechanical) in cancer patients
      undergoing major abdominal or pelvic surgery and in 2) those with an acute
      medical disease requiring hospitalization and who are bedridden. Avoid prevention
      in 3) cancer patients with a central venous catheter and 4) those on
      chemotherapy, radiotherapy or hormonal therapy, except patients with multiple
      myeloma treated with thalidomide/lenalidomide plus high-dose dexamethasone, and
      those with gastrointestinal or lung cancer. Six areas were considered to be
      clinically important, but lacked evidence from the literature and thus required a
      formal consensus (grade D): 1) need of prevention during chemo- radiotherapy or
      hormonal therapy in patients with previous VTE; 2) optimal duration of
      pharmacological prevention in patients who are hospitalized/bedridden for acute
      medical illness; 3) optimal duration of pharmacological prevention in patients
      undergoing major surgery other than abdominal and pelvic; 4) optimal duration of
      pharmacological prevention in myeloma patients receiving thalidomide plus
      dexamethasone; 5) presence of cerebral metastasis as a contraindication to
      pharmacological prevention; 6) prevention in cancer patients undergoing surgery
      by laparoscopic procedures lasting>30min. CONCLUSION: Results of the systematic
      literature review and an explicit approach to consensus techniques have led to
      recommendations for the most clinically important issues in the prevention of VTE
      in cancer patients.

PMID- 21962723
TI  - Can older people with cognitive impairments make effective choices about their
      health and social care? A commentary on Meinow, Parker and Thorslund from an
      English perspective.

PMID- 21962724
TI  - Hormones, context, and "brain gender": a review of evidence from congenital
      adrenal hyperplasia.
AB  - Brain organization theory suggests that steroid hormones during fetal development
      permanently organize the brain for gender, including patterns of sexuality,
      cognition, temperament, and interests that differ by sex. This widely-accepted
      theory has important implications for health, ranging from medical management of
      infants with intersex conditions to suggested etiologies for sex differences in
      autism, depression, and other mental health problems. Studies of genetic females
      with congenital adrenal hyperplasia (CAH), in which high prenatal androgens have
      been linked to both atypical genitals and "masculine" patterns of gender and
      sexuality, are particularly important. Based on a comprehensive review of
      research on CAH, this article demonstrates that such studies have neglected four
      broad categories of variables that plausibly affect psychosexual development: (1)
      physiological effects of CAH, including complex disruption of steroid hormones
      from early development onwards; (2) intensive medical intervention and
      surveillance, which many women with CAH describe as traumatic; (3) direct effects
      of genital morphology on sexuality (versus indirect effects that "masculine"
      genitals may have on gender socialization); and (4) expectations of
      masculinization that likely affect both the development and evaluation of gender
      and sexuality in CAH. Complex and iterative interactions among postnatal
      biological variables, medical interventions, and social context provide a more
      plausible explanation for atypicalities in psychology and behavior that have been
      reported for genetic females with CAH than the conventional explanation that
      early androgens have "masculinized" their brains.

PMID- 21962725
TI  - Analyses related to the development of DSM-5 criteria for substance use related
      disorders: 3. An assessment of Pathological Gambling criteria.
AB  - BACKGROUND: The DSM-5 Substance-Related Disorders Work Group proposed to include
      Pathological Gambling within the current Substance-Related Disorders section. The
      objective of the current report was to assess four possible sets of diagnostic
      criteria for Pathological Gambling. METHODS: Gamblers (N=161) were defined as
      either Pathological or Non-Pathological according to four classification methods.
      (a) Option 1: the current DSM-IV criteria for Pathological Gambling; (b) Option
      2: dropping the "Illegal Acts" criterion, while keeping the threshold at 5
      required criteria endorsed; (c) Option 3: the proposed DSM-5 approach, i.e.,
      deleting "Illegal Acts" and lowering the threshold of required criteria from 5 to
      4; (d) Option 4: to use a set of Pathological Gambling criteria modeled on the
      DSM-IV Substance Dependence criteria. Cronbach's alpha and eigenvalues were
      calculated for reliability, Phi, discriminant function analyses, correlations and
      multivariate regression models were performed for validity and kappa coefficients
      were calculated for diagnostic consistency of each option. RESULTS: All criteria
      sets were reliable and valid. Some criteria had higher discriminant properties
      than others. CONCLUSION: The proposed DSM-5 criteria in Options 2 and 3 performed
      well and did not appear to alter the meanings of the diagnoses of Pathological
      Gambling from DSM-IV. Future work should further explore if Pathological Gambling
      might be assessed using the same criteria as those used for Substance Use
      Disorders.

PMID- 21962726
TI  - African American patients seeking treatment in the public sector: characteristics
      of buprenorphine vs. methadone patients.
AB  - BACKGROUND: To expand its public-sector treatment capacity, Baltimore City made
      buprenorphine treatment accessible to low-income, largely African American
      residents. This study compares the characteristics of patients entering methadone
      treatment vs. buprenorphine treatment to determine whether BT was attracting
      different types of patients. METHODS: Participants consisted of two samples of
      adult heroin-dependent African Americans. The first sample was newly admitted to
      a health center or a mental health center providing buprenorphine (N=200), and
      the second sample was newly admitted to one of two hospital-based methadone
      programs (N=178). The Addiction Severity Index (ASI) and the Friends Supplemental
      Questionnaire were administered at treatment entry and data were analyzed with
      logistic regression. RESULTS: BT participants were more likely to be female
      (p=.017) and less likely to inject (p=.001). Participants with only prior
      buprenorphine treatment experience were nearly five time more likely to enter
      buprenorphine than methadone treatment (p<.001). Those with experience with both
      treatments were more than twice as likely to enter BT (OR=2.7, 95% CI=1.11-6.62;
      p=.028). In the 30 days prior to treatment entry, BT participants reported more
      days of medical problems (p=.002) and depression (p=.044), and were more likely
      to endorse a lifetime history of depression (p<.001). CONCLUSION: Methadone and
      buprenorphine treatment provided in the public sector may attract different
      patient subpopulations. Providing buprenorphine treatment through drug treatment
      programs co-located with a health and mental health center may have accounted for
      their higher rates of medical and psychiatric problems and appears to be useful
      in attracting a diverse group of patients into public-sector funded treatment.

PMID- 21962729
TI  - Hypertrophic cardiomyopathy.
AB  - Hypertrophic cardiomyopathy is a fascinating disease of marked heterogeneity.
      Hypertrophic cardiomyopathy was originally characterized by massive myocardial
      hypertrophy in the absence of known etiology, a dynamic left ventricular outflow
      obstruction, and increased risk of sudden death. It is now well accepted that
      multiple mutations in genes encoding for the cardiac sarcomere are responsible
      for the disease. Complex morphologic and pathophysiologic differences, disparate
      natural history studies, and novel treatment strategies underscore the challenge
      to the practicing cardiologist when faced with the management of the hypertrophic
      cardiomyopathy patient.

PMID- 21962727
TI  - Gastrointestinal malignancies and cardiovascular diseases--non-negligible
      comorbidity in an era of multi-antithrombotic drug use.
AB  - Nowadays, antiplatelet and anticoagulant drug medications are indicated in
      patients with a variety of cardiovascular disorders, such as atrial fibrillation,
      coronary artery disease, and peripheral artery disease. Among cardiology
      patients, regardless of gastrointestinal (GI) protection, we do not infrequently
      encounter those patients who have signs and symptoms that are suggestive of GI
      tract problems. We should bear in mind that such GI signs and symptoms may be
      attributed to GI cancers, as well as to benign or clinically insignificant
      lesions. Several clinical studies have shown, albeit controversially that the
      predictive value of positive fecal occult blood for colorectal malignant neoplasm
      may not be lower in patients taking antithrombotic medication. In addition, it
      has been shown that in patients taking antithrombotic drug(s), diagnosed
      colorectal malignancies are in a relatively earlier phase, suggesting that
      antithrombotic drugs may facilitate the detection of otherwise unrecognized
      cancers. The possibility also exists that certain cardiovascular disease may be
      associated with a higher risk of GI malignant neoplasms. There has been no
      established evidence concerning whether more aggressive GI tract screening will
      reduce the probability of cancer death in cardiology patients; nevertheless, GI
      tract lesions should not be overlooked among cardiology patients, especially when
      unexplained anemia, gastrointestinal symptoms, or positive fecal occult blood
      test is present, and GI tract screening should be performed with appropriate
      timing.

PMID- 21962730
TI  - The effects of the c-kit blocker glivec on the contractile response of urinary
      bladder.
AB  - OBJECTIVES: To investigate the effects of imatinib (Glivec) on the urinary
      bladder contraction and excitation induced by neurostimulation, therefore to
      clarify the relationships between the bladder interstitial cell of Cajal (ICC)
      and the neural signals. METHODS: In in vivo experiments, pelvic nerves of rats
      were stimulated by square-wave pulses. The contractile response was recorded
      before and 40 min after the administration of medications (atropine, Glivec, and
      ketotifen). In in vitro experiments, the bladder contractile response induced by
      acetylcholine with or without Glivec was evaluated. The space relationship
      between ICC and neural fibers were observed with double-labeled fluorescence
      using primary antibodies (anti-c-kit and anti-vesicular acetylcholine
      transferase) and secondary fluorescent antibodies (Alexa 488 and Alexa 594;
      Molecular Probes, Eugene, OR). RESULTS: Atropine and Glivec could significantly
      inhibit the bladder contractile response induced by the electrical stimulation in
      a dose-dependent manner, while ketotifen did not obviously affect bladder
      contractile response. In in vitro experiments, Glivec did not affect
      acetylcholine-induced bladder contractile response. The location of ICC in close
      proximity to cholinergic nerve fibers was confirmed by double-labeled
      fluorescence. CONCLUSIONS: Bladder ICC play an important role as intermediaries
      in the transmission of cholinergic signals from nerve to smooth muscle cells.

PMID- 21962731
TI  - Tacrolimus preconditioning of rat liver allografts impacts glutathione
      homeostasis and early reperfusion injury.
AB  - OBJECTIVE: To characterize the immunosuppressant tacrolimus as a protective
      antioxidant in rat liver transplantation. METHODS: Livers of male Lewis rats
      underwent 24 h of hypothermic preservation in UW solution and were rinsed with
      tacrolimus or placebo directly before transplantation. Markers of liver injury,
      such as enzymes and bile flow, were determined during a 2 h reperfusion period.
      Concentrations of reduced (GSH) and oxidized (GSSG) glutathione were analyzed in
      plasma, bile, and liver tissue for estimation of oxidant stress caused by
      reactive oxygen species (ROS). RESULTS: Administration of tacrolimus (10 ng/mL)
      resulted in decreased ALT plasma levels (1740 +/- 1169 U/l versus 3691 +/- 1144
      U/l; P < 0.05) at 2 h of reperfusion. While endogenous intracellular GSH
      concentrations remained unchanged, GSSG, the oxidation product of GSH, was
      markedly decreased at 2 h of reperfusion in preconditioned livers (47.0 +/- 10.4
      nm/g versus 71.8 +/- 30.6 nm/g; P < 0.05). Correspondingly, GSSG bile
      concentrations (0.19 +/- 0.04 mM versus 0.13 +/- 0.04 mM; P < 0.05) as well as
      plasma GSSG levels (2.4 +/- 0.3 mM versus 1.4 +/- 0.2 mM; P < 0.05) were
      significantly increased upon reperfusion. These findings suggest that tacrolimus
      impacts post-ischemic GSH metabolism when administered as a rinse solution for
      liver allografts through an unknown pathway. CONCLUSION: Hepatocellular injury
      following transplantation was significantly decreased by preconditioning with
      tacrolimus. One possible mechanism of action is the detoxification of ROS through
      the preservation of cytosolic and extracellular GSH/GSSG ratios.

PMID- 21962732
TI  - Laparoscopic appendectomy conversion rates two decades later: an analysis of
      surgeon and patient-specific factors resulting in open conversion.
AB  - BACKGROUND: The role of laparoscopy in appendicitis has gained increased
      popularity but remains controversial. Despite more than 20 y of experience in
      laparoscopy, the nationwide laparoscopic appendectomy (LA) conversion rate is
      reportedly 8.6%. We sought to analyze the impact of patient-specific and surgeon
      specific factors that may contribute to open conversion during LA. MATERIALS AND
      METHODS: A retrospective analysis of 745 LAs (49.9% females and 50.1% males;
      average age of 37.8 y performed at a large tertiary community teaching hospital
      over a 5-y period (May 2004-October 2008) was performed. RESULTS: The overall
      conversion rate for the study period was 4.16% (n = 31). The most common reason
      for open conversion was severe acute inflammation (38.7%). Among converted cases,
      77.42% had no prior abdominal surgery and only 25.81% of cases were converted due
      to adhesions. Females and patients >= 65-y-old had a higher likelihood of open
      conversion (4.30% versus 4.02%, P < 0.99 and 9.26% versus 3.76%, P < 0.1107). The
      overall conversion rate of cases performed by high-volume surgeons (>= 50 total
      cases) in comparison to low-volume surgeons (10-49 total cases) was higher (4.86%
      versus 3.30%, P < 0.39). Conversion rates were lower among surgeons who completed
      residency training after 1990 (3.72% versus 4.35%, P < 0.82) and those with
      fellowship training (1.42% versus 5.18%, P < 0.034). CONCLUSIONS: Laparoscopic
      conversion continues to gain popularity and remains the gold standard procedure
      for appendectomy. Older patients have a higher likelihood of conversion with
      severe acute inflammation being the most common reason for conversion. Additional
      minimally invasive fellowship training was the only surgeon-specific factor that
      significantly impacted conversion rate.

PMID- 21962733
TI  - DC maturation and function are not altered by melanoma-derived immunosuppressive
      soluble factors.
AB  - BACKGROUND: Although melanoma can elicit robust tumor antigen-specific immune
      responses, advanced melanoma is associated with immune tolerance. We have
      previously described several mechanisms of melanoma-induced immunosuppression,
      including the skewing of the immune response towards a Th2 cytokine profile and
      the induction of regulatory T cells. Since dendritic cells (DCs) are potentially
      important players that can direct other cells of the immune system towards a
      cytotoxic, humoral, or regulatory phenotype, we hypothesized that melanoma
      produced factors directly affect the maturation and function of DCs, influencing
      the nature and magnitude of the resulting immune response. MATERIALS AND METHODS:
      To test this hypothesis, immature myeloid-derived DCs (mdDCs) were derived with
      cytokines from CD14+ peripheral blood mononuclear cells (PBMCs) and exposed to
      20% melanoma-conditioned media (MCM). After 2 d, the expression of maturation
      markers and the function of these mdDCs, measured by cytokine production, the
      amount of endocytosis, expression of the inhibitory molecule indoleamine 2,3
      dioxygenase (IDO), and the ability to stimulate T cells were determined. RESULTS:
      We found that incubation with MCM did not inhibit the expression of maturation
      markers or IDO, the production of cytokines, the amount of antigen uptake, or the
      ability to induce T cell proliferation in mixed-lymphocyte reactions by mdDC.
      CONCLUSIONS: These results suggest that the immunosuppressive effects of melanoma
      produced factors are independent of directly measurable changes in mdDC function
      or maturation in vitro.

PMID- 21962734
TI  - Resveratrol counteracts systemic and local inflammation involved in early
      abdominal aortic aneurysm development.
AB  - BACKGROUND: Monocyte activation, macrophage infiltration, vascular oxidative
      stress and matrix proteolysis are inflammatory key steps contributing to
      abdominal aortic aneurysm (AAA) development. A phenotypical and functional
      heterogeneity is recognizable in monocytes by the differential expression of
      surface molecules: CD62L- subset corresponds to activated monocytes, while
      CD143/ACE surface expression increases during their differentiation into
      macrophages. In this work, Resveratrol, which is an antioxidant polyphenol with
      vasoprotective properties, has been evaluated for its potential to limit aneurysm
      development and monocyte-dependent inflammatory response in a model of elastase
      induced AAA. METHODS: Male Sprague-Dawley rats received Resveratrol (10
      mg/kg/die) (Rsv group, n=15) or vehicle (ethanol) alone (Et-OH group, n=15)
      continuously from 7 d before until 14 d after the AAA induction with elastase;
      five littermates were used as untreated control group (Ctr group, n=5). At the
      end of treatment, CD143 and CD62L monocyte expression was analyzed by flow
      cytometry, serum antioxidant capacity was evaluated using the TRAP method and
      circulating TNFalpha, and MMP-9 were measured with ELISA and gel zymography,
      respectively. Aortas were subjected to histology and immunohistochemistry for
      morphological analysis, macrophage infiltration, and MMP-9, TNFalpha, and VEGF
      expression. RESULTS: Resveratrol counteracted the CD62L-monocyte subset
      expansion, CD143 monocyte expression, and circulating levels of MMP-9 activity
      and TNFalpha associated to AAA induction. Similarly, treatment with Resveratrol
      significantly attenuated AAA expansion, vessel wall macrophage infiltration and
      MMP-9, VEGF, and TNFalpha expression, compared with AAA from Et-OH group.
      CONCLUSIONS: Resveratrol limited the monocyte-dependent inflammatory response,
      macrophage differentiation and aortic lumen enlargement in elastase-induced AAA.
      These data suggest that Resveratrol might be tested in selected patients with
      small AAA to modulate the early systemic and local inflammatory response
      associated to AAA progression.

PMID- 21962735
TI  - Commentary on "Preemptive therapy with steroids but not macrolides improves gas
      exchange in caustic-injured donor lungs".

PMID- 21962737
TI  - An evaluation of surgical site infections by wound classification system using
      the ACS-NSQIP.
AB  - BACKGROUND: Surgical wound classification has been the foundation for infectious
      risk assessment, perioperative protocol development, and surgical decision
      making. The wound classification system categorizes all surgeries into: clean,
      clean/contaminated, contaminated, and dirty, with estimated postoperative rates
      of surgical site infection (SSI) being 1%-5%, 3%-11%, 10%-17%, and over 27%,
      respectively. The present study evaluates the associated rates of the SSI by
      wound classification using a large risk adjusted surgical patient database.
      METHODS: A cross-sectional study was performed using the American College of
      Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) dataset
      between 2005 and 2008. All surgical cases that specified a wound class were
      included in our analysis. Patient demographics, hospital length of stay,
      preoperative risk factors, co-morbidities, and complication rates were compared
      across the different wound class categories. Surgical site infection rates for
      superficial, deep incisional, and organ/space infections were analyzed among the
      four wound classifications using multivariate logistic regression. RESULTS: A
      total of 634,426 cases were analyzed. From this sample, 49.7% were classified as
      clean, 35.0% clean/contaminated, 8.56% contaminated, and 6.7% dirty. When
      stratifying by wound classification, the clean, clean/contaminated, contaminated,
      and dirty wound classifications had superficial SSI rates of 1.76%, 3.94%, 4.75%,
      and 5.16%, respectively. The rates of deep incisional infections were 0.54%,
      0.86%, 1.31%, and 2.1%. The rates for organ/space infection were 0.28%, 1.87%,
      2.55%, and 4.54%. CONCLUSION: Using ACS-NSQIP data, the present study
      demonstrates substantially lower rates of surgical site infections in the
      contaminated and dirty wound classifications than previously reported in the
      literature.

PMID- 21962736
TI  - Exogenous hydrogen sulfide protects against traumatic hemorrhagic shock via
      attenuation of oxidative stress.
AB  - OBJECTIVE: This study was designed to investigate the protective effects of
      exogenous hydrogen sulfide (H(2)S) on trauma-hemorrhagic shock (T-H). MATERIALS
      AND METHODS: Forty-eight male Sprague-Dawley rats were anesthetized, while 32
      were subjected to both midline laparotomy and hemorrhagic shock (35-40 mmHg for
      90 min) by bleeding them from the femoral artery. One hour later, resuscitation
      was initiated with Ringer lactate. NaHS (28 MUmol/kg) or vehicle alone was
      administered intraperitoneally at the onset of resuscitation. Two hours later,
      eight animals from each group were re-anesthetized to determine cardiac function,
      blood gas concentrations, and hepatic and renal function. Superoxide dismutase
      activity (SOD), malondialdehyde concentrations (MDA), and the activity of
      myeloperoxidase (MPO) in the serum were measured and pulmonary wet/dry (W/D)
      ratio and histopathologic evaluations performed. RESULTS: NaHS resulted in an
      increase in mean arterial blood pressure, left ventricular pressure and positive
      (+dP/dt(max)) and negative (-dP/dt(max)) first derivatives of pressure as
      compared with the vehicle only group. The pH, PaO(2) and base excess (BE) were
      increased in the NaHS-treated group compared with the vehicle-treated group.
      Aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and
      serum creatinine were reduced in the NaHS-treated group. NaHS also significantly
      reduced the high mortality rate at 24 h otherwise caused by T-H. The NaHS-treated
      group showed a remarkable decrease in MDA and MPO concentrations in plasma and an
      increase in SOD as compared with the vehicle-treated group. Histopathologic
      analysis indicated less edema, congestion, inflammatory cell infiltration and
      necrosis in heart, lung, liver and kidney tissue in NaHS-treated group.
      CONCLUSIONS: The present study demonstrates that exogenous H(2)S administered at
      an appropriate dose confers protective effects after T-H and resuscitation, by
      preventing a decrease in the antioxidant defense system.

PMID- 21962738
TI  - Single-incision laparoscopic cholecystectomy (SILC) using harmonic scalpel.
AB  - BACKGROUND: Single-incision laparoscopic cholecystectomy (SILC) is emerging as a
      potentially less invasive alternative to standard laparoscopic cholecystectomy
      (LC). However, this procedure is technically more complex and time consuming. We
      present our initial experience with SILC using harmonic ACE (HS-SILC) in an
      attempt to simplify the procedure. METHODS: We collected concurrent data on 67
      consecutive patients undergoing HS-SILC by a single surgeon in a university
      affiliated hospital over a period of 9 mo. RESULTS: From May 2010 to February
      2011, 67 consecutive patients underwent an attempted HS-SILC for symptomatic
      cholelithiasis by a single surgeon, with a success rate of 95.5%. Conversion to a
      standard LC was necessary in two patients (2.9%), and conversion to an open
      cholecystectomy was necessary in one patient (1.6%). The average operative time
      was 36.2 min. No injuries to the common bile duct occurred. Postoperative port
      site infection occurred in one patient (1.5%). No perioperative deaths occurred.
      CONCLUSIONS: HS-SILC is safe and feasible. It simplifies the procedure and makes
      operative time less with better cosmetic results and lower rate of conversion to
      multi-incision LC or open cholecystectomy.

PMID- 21962739
TI  - Remote or conventional ischemic preconditioning--local liver metabolism in rats
      studied with microdialysis.
AB  - BACKGROUND: Ischemic preconditioning (IPC) of the liver decreases liver injury
      secondary to ischemia and reperfusion. An attractive alternative to IPC is remote
      ischemic preconditioning (R-IPC), but these two methods have not previously been
      compared. MATERIAL AND METHODS: Eighty-seven rats were randomized into four
      groups: sham operated (n = 15), 1 h segmental ischemia (IRI, n = 24), preceded by
      IPC (n = 24), or R-IPC (n = 24) (to the left hindleg). IPC and R-IPC were
      performed with 10 min ischemia and 10 min of reperfusion. Analyses of liver
      microdialysate (MD), serum transaminase levels, and liver histology were made.
      RESULTS: Rats treated with IPC and R-IPC had significantly lower AST, 71.5 (19.6)
      IU/L respective 96.6 (12.4) at 4 h reperfusion than those subjected to IRI alone,
      155 (20.9), P = 0.0004 and P = 0.04 respectively. IPC also had lower ALT levels,
      41.6 (11.3) IU/L than had IRI 107.4 (15.5), P = 0.003. The MD glycerol was
      significantly higher during ischemia in the R-IPC [759 (84) MUM] and the IRI [732
      (67)] groups than in the IPC 514 (70) group, P = 0.022 and P = 0.046
      respectively. The MD glucose after ischemia was lower in the IPC group 7.1 (1.2)
      than in the IRI group 12.7 (1.6), P = 0.005. Preconditioning to the liver caused
      an direct increase in lactate, glucose and glycerol in the ischemic segment
      compared with the control segment an effect not seen in the R-IPC and IRI groups.
      CONCLUSIONS: IPC affects glucose metabolism in the rat liver, observed with MD.
      IPC reduces liver cell injury during ischemic and reperfusion in rats. R-IPC
      performed over the same length of time as IPC does not have the same effect as
      the latter on ALT levels and MD glycerol; this may suggest that R-IPC does not
      offer the same protection as IPC in this setting of rat liver IRI.

PMID- 21962740
TI  - Use of administrative data to identify colorectal liver metastasis.
AB  - BACKGROUND: The ability to identify patients with colorectal cancer (CRC) liver
      metastasis (LM) using administrative data is unknown. The goals of this study
      were to evaluate whether administrative data can accurately identify patients
      with CRCLM and to develop a diagnostic algorithm capable of identifying such
      patients. MATERIALS AND METHODS: A retrospective cohort study was conducted to
      validate the diagnostic and procedural codes found in administrative databases of
      the Veterans Administration (VA) system. CRC patients evaluated at a major VA
      center were identified (1997-2008, n = 1671) and classified as having liver
      specific ICD-9 and/or CPT codes. The presence of CRCLM was verified by primary
      chart abstraction in the study sample. Contingency tables were created and the
      positive predictive value (PPV) for CRCLM was calculated for each candidate
      administrative code. A multivariate logistic-regression model was used to
      identify independent predictors (codes) of CRCLM, which were used to develop a
      diagnostic algorithm. Validity of the algorithm was determined by discrimination
      (c-statistic) of the model and PPV of the algorithm. RESULTS: Multivariate
      logistic regression identified ICD-9 diagnosis codes 155.2 (OR 9.7 [95% CI 2.5
      38.4]) and 197.7 (84.6 [52.9-135.3]), and procedure code 50.22 (5.9 [1.3-25.5])
      as independent predictors of CRCLM diagnosis. The model's discrimination was
      0.89. The diagnostic algorithm, defined as the presence of any of these codes,
      had a PPV of 87%. CONCLUSIONS: VA administrative databases reliably identify
      patients with CRCLM. This diagnostic algorithm is highly predictive of CRCLM
      diagnosis and can be used for research studies evaluating population-level
      features of this disease within the VA system.

PMID- 21962741
TI  - Effect of protein C gene mutation on coagulation and inflammation in hemorrhagic
      shock.
AB  - INTRODUCTION: Trauma patients are at high risk of complications and death from
      coagulopathy and inflammatory organ failure. Recent evidence implicates protein C
      (PC) as a key mediator of this process. We hypothesized that a mutation in the PC
      gene would ameliorate the inflammatory and coagulopathic response to hemorrhagic
      shock (HS) and resuscitation. METHODS: FHH wild type and PC mutant rats underwent
      controlled hemorrhage for 120 min with 70% of blood volume removed. Rats were
      resuscitated with Ringers lactate (2x shed blood volume) and shed blood. Animals
      were sacrificed 4 h post-HS. Controls were untreated naive rats. RESULTS: AST and
      NFkB lung protein levels were elevated similarly in both WT and mutants compared
      with naive rats. Plasma fibrinogen levels decreased significantly with
      progression of HS compared with baseline (BL) levels and returned towards normal
      4 h after resuscitation. PC activity was similar in both groups at BL (0.5 +/-
      0.08 versus 0.6 +/- 0.14; P = 0.14) and decreased from BL by 53% +/- 24% in WT (P
      =0.08), by 67% +/- 11% in mutants (P = 0.03) at sacrifice, and was not different
      between groups (P = 0.29). CONCLUSIONS: Our model of HS and resuscitation
      produced a hypocoaguable, hyperinflammatory state with increased levels of NFkB
      and decreased levels of fibrinogen and PC levels. The mutated PC did not appear
      to alter these responses in our model of HS and resuscitation.

PMID- 21962742
TI  - Total knee and hip arthroplasty across BMI categories: a feasible option for the
      morbidly obese patient.

PMID- 21962743
TI  - Collagen-gelatin scaffold impregnated with bFGF accelerates palatal wound healing
      of palatal mucosa in dogs.
AB  - BACKGROUND: We have developed a collagen-gelatin sponge (CGS) as a scaffold
      capable of the sustained release of bFGF to improve the healing process of the
      existing collagen scaffold. The aim of this study was to evaluate the efficacy of
      CGS impregnated with basic fibroblast growth factor (bFGF) in palatal wound
      healing in beagles. MATERIALS AND METHODS: Four standardized 6 mm diameter full
      thickness wounds were made in the palate of each dog and covered with CGS
      impregnated with normal saline or bFGF at concentrations of 1 MUg/cm2, 7 MUg/cm2
      and 14 MUg/cm2. One and 2 wk after surgery, the wound area, neoepithelium length,
      thickness, area of regenerated submucosal tissue, and the number and total area
      of neoformed capillaries were evaluated. RESULTS: Two weeks after implantation,
      wounds treated with bFGF 7 MUg/cm2 and 14 MUg/cm2 were completely epithelized,
      while the length of the neoformed epithelium was significantly longer in the 7
      MUg/cm2 group. Groups impregnated with bFGF 7 MUg/cm2 and 14 MUg/cm2 showed
      promoted regeneration of submucosal tissue 2 wk later. The number and area of
      neoformed capillaries were significantly higher in the bFGF 7 MUg/cm2 group than
      in other groups. We conclude that palatal wound healing in the bFGF 7 MUg/cm2
      group was promoted with good neovascularization and showed less contracture than
      other groups. CONCLUSIONS: Our new collagen-gelatin scaffold, CGS, impregnated
      with bFGF, could be a promising treatment to accelerate the regeneration of
      palatal mucosa.

PMID- 21962744
TI  - Comparison of systematic mediastinal lymph node dissection versus systematic
      sampling for lung cancer staging and completeness of surgery.
AB  - BACKGROUND: This self-controlled prospective study was designed to investigate
      the efficacy of systematic sampling (SS), compared with systematic mediastinal
      lymph node dissection (SMLD), for pathologic staging and completeness of surgery.
      METHODS: Over a period of 11 mo, 110 patients with lung cancer were enlisted and
      treated by pulmonary resection. Surgeons systematically sampled mediastinal lymph
      nodes prior to pulmonary resection, and after pulmonary resection SMLD was
      performed to each patient using Mountain's procedure [1]. RESULTS: After SMLD, pN
      status was classified as N0 in 57 cases, N1 in 27, and N2 in 26. SS detected
      38.3% of pooled nodes and 37.6% of pooled positive nodes collected from SMLD.
      Pathologic diagnosis after SS was understaged in nine cases (8.2%) compared with
      staging after SMLD. However, surgery was incomplete in 24 cases (21.8%) if SMLD
      was not performed after sampling. Negative predictive value for SS was 86.8% on
      the right side, and 95.0% on the left. Three categories were generated according
      to pN status: negative nodes in SS and additional negative nodes from SMLD [S(
      )D(-)], negative nodes in SS but additional positive nodes from SMLD [S(-)D(+)],
      and positive nodes in SS [S(+)D(+)]. cN2 (P=0.000) and CEA level (P=0.001) were
      correlated with pN status. There was significant overall survival difference
      between non-N2 group and N2 group (P=0.002). CONCLUSIONS: SMLD may harvest about
      three times of mediastinal lymph nodes compared with SS. SS is more likely to
      affect the completeness of surgery instead of underrating pathologic stage.

PMID- 21962746
TI  - Interplay between redox status and inflammasome activation.
AB  - Several inflammation-related processes, including inflammasome activation and
      interleukin (IL)-1beta secretion, are dependent on redox signaling. However, the
      type of redox response involved as well as the relevant role of pro-oxidant and
      antioxidant events are matters of intense debate. By comparing leukemic myeloid
      cells, healthy monocytes and macrophages, as well as monocytes from patients
      carrying mutations in members of the Nod-like receptor (NLR) gene family, we have
      drawn a model that reconciles previous conflicting hypotheses. We propose that
      the redox state of resting inflammatory cells determines the type and extent of
      redox response to pattern recognition receptor stimulation, which in turn
      dictates the efficiency of inflammasome activation. The impact on genetic and
      acquired inflammatory diseases will be discussed.

PMID- 21962747
TI  - Prevalence and management of urinary tract endometriosis: a clinical case series.
AB  - OBJECTIVE: To report on the prevalence, surgical management, and outcome of
      urinary tract endometriosis (UTE) in a cohort of 221 patients undergoing
      laparoscopic surgery for severe endometriosis. UTE can cause significant
      morbidity, such as silent kidney or progressive renal function loss. Its
      frequency is underestimated and data on laparoscopic management are scarce.
      METHODS: Between 2007 and 2010, 43 patients were eligible for this single-center,
      retrospective study. The inclusion criterion was the presence of UTE (ie, bladder
      and/or ureteral endometriosis). All patients were operated laparoscopically.
      RESULTS: The prevalence of UTE was 19.5% (43/221). There was no correlation
      between bladder and ureteral endometriosis (P >.05). Ureteral endometriosis was
      associated with patient's age (P <.01). Patients with bladder, but not ureteral,
      involvement complained more frequently about dysuria, hematuria, and urinary
      tract infections. Intraoperative and magnetic resonance imaging (MRI) findings
      revealed a moderate to good correlation. UTE was not associated with rectovaginal
      or bowel endometriosis, but rather with involvement of the uterosacral ligaments
      (P <.01). Twenty-two patients with bladder endometriosis were treated by mucosal
      skinning and 11 patients underwent partial cystectomy. Superficial ureteral
      excision was performed in 4 patients, whereas resection with ureteroureterostomy
      was done in 9 patients. There was no difference regarding the intra- and
      postoperative complications in patients with or without UTE. CONCLUSION: In
      severe pelvic endometriosis, involvement of the urinary tract is quite common.
      Laparoscopic management is feasible and safe. Because of the lack of specific
      symptoms, the preoperative diagnosis of ureteral endometriosis still remains a
      challenge. Pelvic MRI represents a useful preoperative diagnostic tool.

PMID- 21962745
TI  - DRiPs solidify: progress in understanding endogenous MHC class I antigen
      processing.
AB  - Defective ribosomal products (DRiPs) are a subset of rapidly degraded
      polypeptides that provide peptide ligands for major histocompatibility complex
      (MHC) class I molecules. Here, recent progress in understanding DRiP biogenesis
      is reviewed. These findings place DRiPs at the center of the MHC class I antigen
      processing pathway, linking immunosurveillance of viruses and tumors to
      mechanisms of specialized translation and cellular compartmentalization. DRiPs
      enable the immune system to rapidly detect alterations in cellular gene
      expression with great sensitivity.

PMID- 21962748
TI  - Parsing the relationship of stigma and insight to psychological well-being in
      psychotic disorders.
AB  - BACKGROUND: It has been postulated that the effects of the stigma of mental
      illness on the psychological well-being of patients is mediated through
      internalization of the stigma. On the other hand, there is reason to suppose that
      simple awareness of public stigma could also have an impact to the extent that an
      individual is aware of being ill. AIM: To investigate whether internalization of
      the stigma of having a psychotic disorder and an interaction between perceived
      public stigma and awareness of being ill make independent contributions to the
      prediction of psychological well-being in patients with psychotic disorder.
      METHOD: 102 patients in an early intervention program for psychoses were assessed
      for awareness of public stigma, internalization of stigmatizing beliefs, insight
      and various aspects of psychological well-being including self-esteem,
      depression, anxiety, anger/hostility and engulfment. RESULTS: Internalization of
      stigma was associated with lower levels of psychological well-being. In addition,
      perception of public stigma also contributed to lower well-being for those
      individuals with greater awareness of being ill. CONCLUSIONS: While
      internalization of stigma is an important contribution to psychological well
      being in patients with psychosis, awareness of public stigma, even if this is not
      internalized, also is associated with lower self-esteem, and greater anxiety,
      anger/hostility, and engulfment in patients with better insight.

PMID- 21962749
TI  - Learning to read the oceans genomics of marine phytoplankton.
AB  - The phytoplankton are key members of marine ecosystems, generating about half of
      global primary productivity, supporting valuable fisheries and regulating global
      biogeochemical cycles. Marine phytoplankton are phylogenetically diverse and are
      comprised of both prokaryotic and eukaryotic species. In the last decade, new
      insights have been gained into the ecology and evolution of these important
      organisms through whole genome sequencing projects and more recently, through
      both transcriptomics and targeted metagenomics approaches. Sequenced genomes of
      cyanobacteria are generally small, ranging in size from 1.8 to 9 million base
      pairs (Mbp). Eukaryotic genomes, in general, have a much larger size range and
      those that have been sequenced range from 12 to 57 Mbp. Whole genome sequencing
      projects have revealed key features of the evolutionary history of marine
      phytoplankton, their varied responses to environmental stress, their ability to
      scavenge and store nutrients and their unique ability to form elaborate cellular
      coverings. We have begun to learn how to read the 'language' of marine
      phytoplankton, as written in their DNA. Here, we review the ecological and
      evolutionary insights gained from whole genome sequencing projects, illustrate
      how these genomes are yielding information on marine natural products and
      informing nanotechnology as well as make suggestions for future directions in the
      field of marine phytoplankton genomics.

PMID- 21962750
TI  - Biology of deep-water octocorals.

PMID- 21962751
TI  - Tipping points, thresholds and the keystone role of physiology in marine climate
      change research.
AB  - The ongoing and future effects of global climate change on natural and human
      managed ecosystems have led to a renewed interest in the concept of ecological
      thresholds or tipping points. While generalizations such as poleward range shifts
      serve as a useful heuristic framework to understand the overall ecological
      impacts of climate change, sophisticated approaches to management require
      spatially and temporally explicit predictions that move beyond these
      oversimplified models. Most approaches to studying ecological thresholds in
      marine ecosystems tend to focus on populations, or on non-linearities in physical
      drivers. Here we argue that many of the observed thresholds observed at community
      and ecosystem levels can potentially be explained as the product of non
      linearities that occur at three scales: (a) the mechanisms by which individual
      organisms interact with their ambient habitat, (b) the non-linear relationship
      between organismal physiological performance and variables such as body
      temperature and (c) the indirect effects of physiological stress on species
      interactions such as competition and predation. We explore examples at each of
      these scales in detail and explain why a failure to consider these non
      linearities - many of which can be counterintuitive - can lead to Type II errors
      (a failure to predict significant ecological responses to climate change).
      Specifically, we examine why ecological thresholds can occur well before
      concomitant thresholds in physical drivers are observed, i.e. how even small
      linear changes in the physical environment can lead to ecological tipping points.
      We advocate for an integrated framework that combines biophysical, ecological and
      physiological methods to generate hypotheses that can be tested using
      experimental manipulation as well as hindcasting and nowcasting of observed
      change, on a spatially and temporally explicit basis.

PMID- 21962752
TI  - Social aggregation in the pelagic zone with special reference to fish and
      invertebrates.
AB  - Aggregations of organisms, ranging from zooplankton to whales, are an extremely
      common phenomenon in the pelagic zone; perhaps the best known are fish schools.
      Social aggregation is a special category that refers to groups that self-organize
      and maintain cohesion to exploit benefits such as protection from predators, and
      location and capture of resources more effectively and with greater energy
      efficiency than could a solitary individual. In this review we explore general
      aggregation principles, with specific reference to pelagic organisms; describe a
      range of new technologies either designed for studying aggregations or that could
      potentially be exploited for this purpose; report on the insights gained from
      theoretical modelling; discuss the relationship between social aggregation and
      ocean management; and speculate on the impact of climate change. Examples of
      aggregation occur in all animal phyla. Among pelagic organisms, it is possible
      that repeated co-occurrence of stable pairs of individuals, which has been
      established for some schooling fish, is the likely precursor leading to networks
      of social interaction and more complex social behaviour. Social network analysis
      has added new insights into social behaviour and allows us to dissect
      aggregations and to examine how the constituent individuals interact with each
      other. This type of analysis is well advanced in pinnipeds and cetaceans, and
      work on fish is progressing. Detailed three-dimensional analysis of schools has
      proved to be difficult, especially at sea, but there has been some progress
      recently. The technological aids for studying social aggregation include video
      and acoustics, and have benefited from advances in digitization, miniaturization,
      motion analysis and computing power. New techniques permit three-dimensional
      tracking of thousands of individual animals within a single group which has
      allowed novel insights to within-group interactions. Approaches using theoretical
      modelling of aggregations have a long history but only recently have hypotheses
      been tested empirically. The lack of synchrony between models and empirical data,
      and lack of a common framework to schooling models have hitherto hampered
      progress; however, recent developments in this field offer considerable promise.
      Further, we speculate that climate change, already having effects on ecosystems,
      could have dramatic effects on aggregations through its influence on species
      composition by altering distribution ranges, migration patterns, vertical
      migration, and oceanic acidity. Because most major commercial fishing targets
      schooling species, these changes could have important consequences for the
      dependent businesses.

PMID- 21962753
TI  - Preferential sexual transmission of pseudorabies virus in feral swine populations
      may not account for observed seroprevalence in the USA.
AB  - This paper compares the behavior of two competing models for the transmission of
      pseudorabies virus in feral swine in the USA. In first model, horizontal (non
      sexual) density dependent transmission is the only transmission modality. In the
      second model, the only transmission modality is sexual transmission between
      mature males and females. The comparison of model behavior was carried out to
      test the hypothesis that preferential sexual transmission of PRV in feral swine
      can account for the seroprevalence observed in the field. The observed range of
      seroprevalence of PRV in mature feral swine in the USA is consistent with a
      preferential sexual transmission only if the feral swine mating system is a
      random mating system or a polygynous system in which there is a relatively large
      rate of acquisition of new mates. The observed range of seroprevalence of PRV in
      mature feral swine in the USA is not consistent with a preferential sexual
      transmission if there is mate guarding. This is important because the National
      Pseudorabies Surveillance Plan deems monitoring the risk of PRV introduction from
      feral swine to be a "minor objective" both in terms of the scope of the plan and
      with respect to the resources allocated. The rationale for this statement was
      derived from experimental studies, which suggested that the PRV indigenous to
      feral swine in the USA is preferentially sexually transmitted.

PMID- 21962755
TI  - Psychogenic nonepileptic seizures: characterization of two distinct patient
      profiles on the basis of trauma history.
AB  - This prospective study investigated and compared psychiatric features of 25
      consecutive patients with psychogenic nonepileptic seizures (PNES) on the basis
      of presence of reported trauma. The "trauma" group comprised 19 patients (76%)
      and the "no-trauma" group comprised 6 patients (34%). We compared history of
      PNES, psychiatric comorbidity, alexithymia, and symptoms of dissociation. The
      study clearly characterized two distinct profiles of patients with PNES on the
      basis of trauma history. Patients with trauma had at least one psychiatric
      comorbidity or antecedent (vs 0% in the no-trauma group NT, P<0.001) and a higher
      median score of dissociation (P<0.001). Patients without trauma had more frequent
      "frustration situations" as a factor triggering PNES and subsequent sick leaves
      as perpetuating factors (P=0.001). Trauma antecedents correlated with a high rate
      of psychiatric comorbidity and a strong dissociative mechanism. Patients without
      trauma had no psychiatric comorbidity and a weaker dissociative mechanism.

PMID- 21962754
TI  - Multiple system atrophy: a clinical and neuropathological perspective.
AB  - Multiple system atrophy (MSA) is a neurodegenerative disease involving motor
      abnormalities that include akinesia, rigidity and postural instability. While
      improved diagnostic criteria have aided the accurate diagnosis of MSA, our
      understanding of the neuropathological aspects underlying MSA was bolstered by
      the identification of alpha-synuclein (alpha-syn) as the primary constituent of
      the abnormal protein aggregates observed in the brains of MSA patients. The
      generation of transgenic animal models of MSA coupled with an increasing
      understanding of the biochemical structure and function of alpha-syn has
      highlighted a number of key pathological pathways thought to underlie the
      neurodegeneration observed in MSA. This review summarizes key findings in the
      field, discusses current areas of debate, and describes current experimental
      approaches towards disease-modifying therapies.

PMID- 21962756
TI  - "MRI-negative PET-positive" temporal lobe epilepsy: invasive EEG findings,
      histopathology, and postoperative outcomes.
AB  - The aim of this retrospective study was to analyze invasive EEG findings,
      histopathology, and postoperative outcomes in patients with MRI-negative, PET
      positive temporal lobe epilepsy (TLE) (MRI-/PET+TLE) who had undergone epilepsy
      surgery. We identified 20 patients with MRI-/PET+TLE (8.4% of all patients with
      TLE who had undergone surgery; 11 men, 9 women). Of the 20 patients, 16 underwent
      invasive EEG. The temporal pole and hippocampus were involved in the seizure
      onset zone in 62.5% of the patients. We did not identify a lateral temporal or
      extratemporal seizure onset in any patient. Of the 20 patients, 17 had follow-up
      periods >1 year (mean follow-up=3.3 years). At the final follow-up, 70.6%
      patients were classified as Engel I, 5.8% of patients as Engel II, and 11.8% of
      patients as Engel III and IV (11.8%). Histopathological evaluation showed no
      structural pathology in any resected hippocampus in 58% of all evaluated temporal
      poles. The most common pathology of the temporal pole was focal cortical
      dysplasia type IA or IB. MRI-/PET+TLE should be delineated from other
      "nonlesional TLE." The ictal onset in these patients was in each case in the
      temporal pole or hippocampus, rather than in the lateral temporal neocortex.
      Standard surgery produced a good postoperative outcome, comparable to that for
      patients with lesional TLE. Histopathological findings were limited: the most
      common pathology was focal cortical dysplasia type I.

PMID- 21962757
TI  - Assessment of the convulsant liability of antidepressants using zebrafish and
      mouse seizure models.
AB  - In the past, antidepressants have been thought to possess proconvulsant
      properties. This assumption remains controversial, however, because
      anticonvulsant effects have been attributed to certain antidepressants. To date,
      it remains unclear which antidepressants can be used for the treatment of
      patients with epilepsy with depression. The present study was designed to
      determine the anticonvulsant and/or proconvulsant effects of three
      antidepressants (citalopram, reboxetine, bupropion) against pilocarpine- and
      pentylenetetrazole-induced acute seizures in larval zebrafish and mice. In
      zebrafish, all antidepressants were anticonvulsant in the pentylenetetrazole
      model. In addition, citalopram was anticonvulsant in the zebrafish pilocarpine
      model, whereas reboxetine and bupropion were without significant effect. In mice
      all three antidepressants increased some thresholds for pentylenetetrazole
      induced convulsive-like behaviors at varying doses, whereas thresholds for
      pilocarpine-induced convulsive-like behaviors were generally lowered,
      particularly at the highest doses tested. In general we conclude that the
      convulsant liability of antidepressants is model and concentration dependent.

PMID- 21962758
TI  - Leflunomide in dermatology.
AB  - Leflunomide is an oral disease-modifying antirheumatic drug administered to
      patients with rheumatoid and psoriatic arthritis. This drug inhibits
      dihydroorotate dehydrogenase, an enzyme critical in the production of
      intracellular pyrimidines, and down-regulates tumor necrosis factor-alfa
      activity. Leflunomide has demonstrated usefulness in treating cutaneous psoriasis
      along with other dermatologic and rheumatologic conditions.

PMID- 21962759
TI  - Integrating clinical/dermatoscopic findings and fluorescence in situ
      hybridization in diagnosing melanocytic neoplasms with less than definitive
      histopathologic features.
AB  - BACKGROUND: Early diagnosis of melanoma remains of paramount importance, because
      it has been widely demonstrated that survival is strongly related to Breslow
      thickness. Several studies have shown that dermatoscopy improves accuracy in the
      diagnosis of melanoma. Although histopathology is considered the gold standard to
      differentiate melanoma from nevi, there are some cases of melanoma in which the
      histopathologic features are less than definitive. It has also been demonstrated
      that fluorescence in situ hybridization can be used to differentiate melanomas
      from nevi based on chromosomal copy number aberrations. OBJECTIVE: In this study
      we present a case series to demonstrate the value of combining fluorescence in
      situ hybridization and dermatoscopy/clinical history to enhance diagnostic
      capability for selected cases of early melanoma. METHODS: Cases were identified
      that had dermatoscopic findings or clinical history highly suggestive of melanoma
      and fluorescence in situ hybridization evaluation positive for melanoma, but
      histopathologic features that were less than definitive. Two dermatopathologists
      performed independent histologic analysis of specimens and two dermatologists
      experienced in dermatoscopy reviewed dermatoscopic and clinical data. RESULTS:
      Nine cases meeting inclusion criteria were identified. In 6 cases the histologic
      differential diagnosis was dysplastic nevus versus early melanoma whereas in 3
      cases the differential diagnosis included Spitz nevus versus early melanoma.
      LIMITATIONS: Limitations of this study include restrictive inclusion criteria and
      study design restricted to a case series. CONCLUSION: This exploratory study
      demonstrates that in a subset of early melanoma cases, combining multiple
      diagnostic modalities such as dermatoscopy and molecular techniques with
      histology enhances detection of early melanoma.

PMID- 21962760
TI  - Simple and rapid simultaneous profiling of minor components of honey by size
      exclusion chromatography (SEC) coupled to ultraviolet diode array detection (UV
      DAD), combined with chemometric methods.
AB  - This paper discusses the importance of profiling UV-responsive components,
      properly integrated with chemometric techniques, in detecting indicative
      parameters for quality control of honey. The minor components in honeys of
      different botanical and geographical origins were investigated by size SEC-UV
      DAD. We diluted honey with mobile phase before injection into the chromatographic
      apparatus and a single chromatographic run gave a fast profile of high- (proteins
      and enzymes), intermediate- (e.g. terpenoid glycosides in lime tree honey) and
      low-molecular-weight components (secondary metabolites, e.g. kynurenic acid in
      chestnut honey). The analysis of a total number of 32 honey samples from
      different regions (Italy, Western Balkan countries, Brazil, Cameroon, Kenya) and
      of different botanical origins (herbal flower and arboreal flower
      nectars/honeydews) showed peculiar and characteristic distribution of these
      markers, which were basically related to their floral origin. Chemometric
      examination carried out using principal component analysis (PCA) and hierarchical
      cluster analysis (HCA) of the chromatograms (RT vs. absorption) detected four
      main clusters in which the groups of (i) chestnut honeys, (ii) honeys from rain
      forests and (iii) counterfeit/adulterated honeys were clearly separated from the
      main group of flower nectar honeys. The method is fast, requiring minimal sample
      handling, and the chromatographic data can be analyzed by multivariate
      statistical techniques to obtain descriptive information about the honey's
      quality and composition.

PMID- 21962761
TI  - Size exclusion chromatography with evaporative light scattering detection as a
      method for speciation analysis of polydimethylsiloxanes. III. Identification and
      determination of dimeticone and simeticone in pharmaceutical formulations.
AB  - The pharmaceutical industry is one of the more important sectors for the use of
      polydimethylsiloxanes (PDMS), which belong to the organosilicon polymers. In
      drugs for internal use, they are used as an active pharmaceutical ingredient
      (API) called dimeticone or simeticone. Due to their specific chemical nature,
      PDMS can have different degrees of polymerization, which determine the molecular
      weight and viscosity. The Pharmacopoeial monographs for dimeticone and
      simeticone, only give the permitted polymerization and viscosity range. It is,
      however, essential to know also the degree of polymerization or the specific
      molecular weight of PDMS that are present in pharmaceutical formulations. In the
      literature there is information about the impact of particle size, and thus
      molecular weight, on the toxicity, absorption and migration in living organisms.
      This study focused on the use of a developed method - the exclusion
      chromatography with evaporative light scattering detector (SEC-ELSD) - for
      identification and determination of dimeticone and simeticone in various
      pharmaceutical formulations. The method had a high degree of specificity and was
      suitable for speciation analysis of these polymers. So far the developed method
      has not been used in the control of medicinal products containing dimeticone or
      simeticone.

PMID- 21962762
TI  - Report of two Chinese patients suffering from CLCN7-related osteopetrosis and
      root dysplasia.
AB  - Osteopetrosis is a group of genetic bone disorders. There are three types of
      osteopetrosis: autosomal recessive osteopetrosis (ARO), autosomal dominant
      osteopetrosis type II (ADO II), and intermediate autosomal recessive
      osteopetrosis (IARO). The prevalence of ADO II is about 1:100,000, while no more
      than 20 cases of IARO have been reported worldwide. We present the first Chinese
      IARO patient with a novel homozygous variant in CLCN7 gene (p. Pro470Leu) and an
      ADO II patient with a heterozygous variant in CLCN7 gene (p. Arg286Trp). In
      addition to general osteosclerosis, the striking features of these two patients
      are unerupted teeth with root dysplasia. We speculate that ClC-7 in different
      tooth cells may contribute directly to the root development, the defect of ClC-7
      may have a dose dependent effect on the phenotype of root dysplasia, and the
      tooth position may also affect the root phenotype with dysfunctional ClC-7.

PMID- 21962763
TI  - Right visual field advantage for perceived contrast: correlation with an auditory
      bias and handedness.
AB  - Studies have suggested that supramodal attentional resources are biased rightward
      due to asymmetric spatial fields of the two hemispheres. This bias has been
      observed especially in right-handed subjects. We presented left and right-handed
      subjects with brief uniform grey visual stimuli in either the left or right
      visual hemifield. Consistent with the proposed asymmetry in attentional
      resources, right-handed subjects estimated right hemifield targets as having a
      higher contrast than physically identical stimuli presented in the left
      hemifield. Left-handed participants did not show a systematic rightward or
      leftward bias. However, the group of left-handed participants also took part in a
      dichotic listening experiment whose results showed that visual bias score
      correlated positively with ear-advantage in dichotic listening. Our results are
      consistent with the view that supramodal processing resources are biased towards
      the right hemispace, and that this bias is influenced by handedness.

PMID- 21962764
TI  - Using next generation sequencing to identify yellow fever virus in Uganda.
AB  - In October and November 2010, hospitals in northern Uganda reported patients with
      suspected hemorrhagic fevers. Initial tests for Ebola viruses, Marburg virus,
      Rift Valley fever virus, and Crimean Congo hemorrhagic fever virus were negative.
      Unbiased PCR amplification of total RNA extracted directly from patient sera and
      next generation sequencing resulted in detection of yellow fever virus and
      generation of 98% of the virus genome sequence. This finding demonstrated the
      utility of next generation sequencing and a metagenomic approach to identify an
      etiological agent and direct the response to a disease outbreak.

PMID- 21962765
TI  - Chronic bilateral subthalamic stimulation after anterior callosotomy in drug
      resistant epilepsy: long-term clinical and functional outcome of two cases.
AB  - We explored the efficacy and safety of bilateral SubThalamic Nucleus (STN)
      stimulation in two subjects suffering from drug-resistant epilepsy even after
      anterior callosotomy. Case 1 had about 65% decrease of partial motor seizures and
      the complete disappearance of tonic-clonic generalized attacks. Case 2, with
      sudden drop (atonic) attacks, partial complex seizures, atypical absences and
      rare tonic-clonic seizures, showed no meaningful reduction of fits and a
      stimulation associated atypical absence rate increase.

PMID- 21962766
TI  - [Coronary disease extension determines mobilization of endothelial progenitor
      cells and cytokines after a first myocardial infarction with ST elevation].
AB  - INTRODUCTION AND OBJECTIVES: Multivessel coronary disease is still a
      postinfarction prognostic marker despite new forms of reperfusion, such as
      primary angioplasty. The aim of this study was to determine the time sequence of
      various sets of endothelial progenitor cells and angiogenic cytokines (vascular
      endothelial growth factor, hepatocyte growth factor) according to the degree of
      extension of the postinfarction coronary disease. METHODS: We studied the release
      kinetics in 32 patients admitted for a first myocardial infarction with ST
      elevation, grouped according to whether they had single or multivessel disease,
      and 26 controls. RESULTS: The patients had a higher number of endothelial
      progenitor cells and angiogenic cytokines than the controls at all 3 measurements
      (admission, day 3, and day 7) of the following subsets: CD34, CD34+CD133+,
      CD34+KDR+, and CD34+CD133+KDR+CD45+(weak); this latter was higher on day 7. The
      levels of these cell subsets were all higher in the patients with single-vessel
      disease and at all 3 measurements. The vascular endothelial growth factor levels
      were raised during the first week and the hepatocyte growth factor showed an
      early peak on admission for infarction. No significant differences were seen in
      the cytokines according to coronary disease extension. CONCLUSIONS: Although the
      release kinetics of different subsets of endothelial progenitor cells in patients
      with a first acute myocardial infarction with ST elevation was similar in those
      with single vessel disease to those with multivessel disease, the number of
      circulating endothelial progenitor cells was greater in the patients with single
      vessel disease. The vascular endothelial growth factor levels were raised during
      the first postinfarction week and the hepatocyte growth factor were higher on
      admission.

PMID- 21962767
TI  - Ventricular fibrillation, an emergency in electrophysiology.

PMID- 21962769
TI  - Outcome of extremely low birth weight infants: what's new in the third
      millennium? Neuropsychological profiles at four years.
AB  - BACKGROUND: Extremely low birth weight (ELBW) infants, even those not presenting
      severe neuromotor sequelae, continue to be at risk of developing multiple,
      complex disorders involving the cognitive, emotional and behavioural domains.
      Follow-up protocols are able, in the short term, to identify subjects at risk of
      developing major sequelae, however they fail to identify all children at risk of
      developing disorders. AIMS: To investigate the cognitive, neuropsychological and
      behavioural outcomes of a sample of ELBW children at the age of four years in
      order to identify characteristic profiles. STUDY DESIGN: Longitudinal study.
      SUBJECTS: 16 healthy ELBW children born in 2005 and followed up until the age of
      four. OUTCOME MEASURE: Performances on standardised tests evaluating
      intelligence, memory, cognitive visual functions, attention, and executive
      functions. RESULTS: General intelligence was within normal range. Cognitive
      profile showed mild or moderate deficits with different levels of involvement in
      many of the examined functions, in particular executive functions, attention and
      naming. CONCLUSION: There emerged a wide-ranging spectrum of weaknesses and
      deficits involving all the functions examined, which together give rise to a
      dysexecutive syndrome. Analysis of cognitive profiles showed that the sample
      could be divided into two subgroups of subjects that differ in the quality of
      their global cognitive and behavioural functioning. Our results confirm the need
      to continue follow up of ELBW children until school age, as this will allow early
      detection of at-risk children and the planning of timely preventive
      interventions.

PMID- 21962770
TI  - Evidence based management guidelines for the detection and treatment of
      congenital CMV.
AB  - CMV is the most common congenital infection in newborns worldwide. Congenital CMV
      causes sensorineural hearing loss in a significant proportion of infected
      newborns, while the majority of newborns are asymptomatic. In the last three
      years there have been significant advances in the diagnosis and treatment of
      congenital CMV. We have developed practical evidence based guidelines for the
      management of congenital CMV.

PMID- 21962771
TI  - Oral and nonoral sensorimotor interventions facilitate suck-swallow-respiration
      functions and their coordination in preterm infants.
AB  - BACKGROUND: Preterm infants are at high risk of encountering oral feeding
      difficulties. Early sensorimotor interventions may improve oral feeding skills in
      preterm infants. AIM: To further explore the effects of an oral (O),
      tactile/kinesthetic (T/K), and combined (O+T/K) sensorimotor intervention on
      preterm infants' nutritive sucking, swallowing and their coordination with
      respiration. STUDY DESIGN: Seventy-five infants (29 [0.3, standard error of mean,
      SEM] weeks gestation, 49 males/26 females) were randomly assigned to an O group
      involving sensorimotor input to the oral structures; a T/K group involving
      sensorimotor input to the trunk and limbs; a combined (O+T/K) group; and a
      control group. OUTCOME MEASURES: Stage of sucking, suction and expression
      amplitudes (mmHg), suck-swallow ratio, stability of suck-swallow interval, and
      swallow-respiration patterns. RESULTS: The O group had significantly more
      advanced sucking stages, and greater suction and expression amplitudes than
      controls [p<=0.035, effect size (ES) >0.6]. The suck-swallow ratio and stability
      of suck-swallow intervals did not significantly differ among groups (p>=0.181,
      ES<=0.3). The three interventions led to fewer swallows bracketed by prolonged
      respiratory pauses compared to controls (pause-swallow-pause, p<=0.044, ES>=0.7).
      The T/K and combined (O+T/K) groups had greater occurrence of swallows bracketed
      by expiration than the control and O groups (expiration-swallow-expiration,
      p<=0.039, ES>=0.3). CONCLUSION: The O intervention enhanced specific components
      of nutritive sucking. All three interventions resulted in improved swallow
      respiration coordination. Sensorimotor interventions have distributed beneficial
      effects that go beyond the specific target of input.

PMID- 21962772
TI  - CBRC and psychosocial counselling: assessing needs and developing an ethical
      framework for practice.
AB  - Encountering infertility and involuntary childlessness and undergoing infertility
      treatment are acknowledged as stressful experiences that impact on individuals'
      psychological and emotional health - and for which access to psychosocial
      counselling by a skilled mental health professional may be beneficial. Evidence
      of patients', gamete donors' and surrogates' experiences indicates that
      utilization of infertility treatment in another country may not only exacerbate
      these psychosocial adversities, but may also pose additional risks to the
      psychological or physical health of participants, thus further emphasizing the
      need for competent psychosocial counselling services in cross-border reproductive
      care. However, this is a largely neglected topic in recent discussions of both
      CBRC itself and of infertility counselling practice. This paper extends the
      previous work undertaken by two of the authors to begin to map out practice
      issues within an ethical framework for counsellors when working with clients,
      donors, surrogates, individuals conceived following infertility treatment and
      existing children in clients', donor's and surrogates' families where cross
      border reproductive treatment is considered or undertaken.

PMID- 21962773
TI  - Assisted reproduction on treacherous terrain: the legal hazards of cross-border
      reproductive travel.
AB  - The growing phenomenon of cross-border reproductive travel has four significant
      legal dimensions. First, laws that ban or inhibit access to assisted reproductive
      procedures in one country lead patients and physicians to travel to other
      countries to acquire, to contribute to or to provide assisted reproductive
      services. Such laws may include provisions that criminalize those who assist or
      advise patients to undertake such travel. Second, the law may expressly
      criminalize crossing borders to obtain, to be a donor for or to perform certain
      procedures. Third, the law may interfere with the ultimate goal of reproductive
      travellers by refusing to recognize them as the parents of the child they have
      crossed borders to conceive. Finally, facilitating cross-border reproductive
      travel may expose physicians, attorneys and brokers to malpractice or other civil
      liability. This article explores these legal dimensions of cross-border
      reproductive care and uses the legal doctrines of proportionality,
      extraterritoriality and comity to assess the legality and normative validity of
      governmental efforts to curb or limit assisted reproductive practices.

PMID- 21962774
TI  - Autoimmune regulator (AIRE) contributes to Dectin-1-induced TNF-alpha production
      and complexes with caspase recruitment domain-containing protein 9 (CARD9),
      spleen tyrosine kinase (Syk), and Dectin-1.
AB  - BACKGROUND: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy
      (APECED) syndrome is a complex immunologic disease caused by mutation of the
      autoimmune regulator (AIRE) gene. Autoimmunity in patients with APECED syndrome
      has been shown to result from deficiency of AIRE function in transcriptional
      regulation of thymic peripheral tissue antigens, which leads to defective T-cell
      negative selection. Candidal susceptibility in patients with APECED syndrome is
      thought to result from aberrant adaptive immunity. OBJECTIVE: To determine
      whether AIRE could function in anticandidal innate immune signaling, we
      investigated an extrathymic role for AIRE in the immune recognition of beta
      glucan through the Dectin-1 pathway, which is required for defense against
      Candida species. METHODS: Innate immune signaling through the Dectin-1 pathway
      was assessed in both PBMCs from patients with APECED syndrome and a monocytic
      cell line. Subcellular localization of AIRE was assessed by using confocal
      microscopy. RESULTS: PBMCs from patients with APECED syndrome had reduced TNF
      alpha responses after Dectin-1 ligation but in part used a Raf-1-mediated pathway
      to preserve function. In the THP-1 human monocytic cell line, reducing AIRE
      expression resulted in significantly decreased TNF-alpha release after Dectin-1
      ligation. AIRE formed a transient complex with the known Dectin-1 pathway
      components phosphorylated spleen tyrosine kinase and caspase recruitment domain
      containing protein 9 after receptor ligation and localized with Dectin-1 at the
      cell membrane. CONCLUSION: AIRE can participate in the Dectin-1 signaling
      pathway, indicating a novel extrathymic role for AIRE and a defect that likely
      contributes to fungal susceptibility in patients with APECED syndrome.

PMID- 21962776
TI  - The third rail: engineering safe travel for the physician community.

PMID- 21962775
TI  - Differential neural activity and connectivity for processing one's own face: a
      preliminary report.
AB  - The experience of self is unique and pivotal to clinically relevant cognitive and
      emotional functions. However, well-controlled data on specialized brain regions
      and functional networks underlying the experience of self remain limited. This
      functional magnetic resonance imaging study investigated neural activity and
      connectivity specific to processing one's own face in healthy women by examining
      neural responses to the pictures of the subjects' own faces in contrast to faces
      of their own mothers, female friends and strangers during passive viewing,
      emotional and self-relevance evaluations. The processing of one's own face in
      comparison to processing of familiar faces revealed significant activity in right
      anterior insula (AI) and left inferior parietal lobule (IPL), and less activity
      in right posterior cingulate/precuneus (PCC/PCu) across all tasks. Further, the
      seed-based correlation analysis of right AI, and left IPL, showed differential
      functional networks in self and familiar faces contrasts. There were no
      differences in valence and saliency ratings between self and familiar others. Our
      preliminary results suggest that the self-experience cued by self-face is
      processed predominantly by brain regions and related networks that link
      interoceptive feelings and sense of body ownership to self-awareness and less by
      regions of higher order functioning such as autobiographical memories.

PMID- 21962777
TI  - The soothsayer of doom.

PMID- 21962778
TI  - Autumn's other contest.

PMID- 21962779
TI  - How IT tools can help improve current protocolling performance gaps.

PMID- 21962780
TI  - Learning to lead: best practices for getting started.

PMID- 21962782
TI  - Unintended consequences of health care legislation.
AB  - Unintended consequences of health care legislation threaten the financial and
      social well-being of the United States. Examples of major legislation resulting
      in unintended and unforeseen consequences include the Social Security Amendments
      Acts of 1989 and 1993 (the Stark laws), the Balanced Budget Act of 1997, and the
      Social Security Amendments Act of 1965 (Medicare and Medicaid). Each of these has
      had unintended financial and social outcomes. Spending for Medicare and Medicaid
      now equals an unsustainable 23% of the federal budget. Major reasons for
      unintended consequences include failure to appreciate the complexity of the
      issues, the open-ended nature of medical advances with attendant increases in
      costs, the inducement of change in behaviors in response to legislation, and the
      moral hazard of people spending other people's money. Actions that should be
      considered to avoid unintended consequences include more involvement of health
      professionals in the design of legislation, the inclusion of triggers to target
      review of legislatively defined programs, and the setting of time limits for sun
      setting legislation. The ACR has played an important advocacy role and should
      continue to offer input to legislators, federal policymakers, and other
      stakeholders. Many opportunities exist to address the current financial situation
      by reducing the amount of unnecessary care delivered. Both major US political
      parties need to find the political will to compromise to chart the way forward.
      Some level of sacrifice is likely to be necessary from patients and providers and
      other stakeholders.

PMID- 21962781
TI  - ACR Appropriateness Criteria(r) chronic chest pain--high probability of coronary
      artery disease.
AB  - Imaging is valuable in determining the presence, extent, and severity of
      myocardial ischemia and the severity of obstructive coronary lesions in patients
      with chronic chest pain in the setting of high probability of coronary artery
      disease. Imaging is critical for defining patients best suited for medical
      therapy or intervention, and findings can be used to predict long-term prognosis
      and the likely benefit from various therapeutic options. Chest radiography,
      radionuclide single photon-emission CT, radionuclide ventriculography, and
      conventional coronary angiography are the imaging modalities historically used in
      evaluating suspected chronic myocardial ischemia. Stress echocardiography, PET,
      cardiac MRI, and multidetector cardiac CT have all been more recently shown to be
      valuable in the evaluation of ischemic heart disease. Other imaging techniques
      may be helpful in those patients who do not present with signs classic for angina
      pectoris or in those patients who do not respond as expected to standard
      management. The ACR Appropriateness Criteria((r)) are evidence-based guidelines
      for specific clinical conditions that are reviewed every 2 years by a
      multidisciplinary expert panel. The guideline development and review include an
      extensive analysis of current medical literature from peer-reviewed journals and
      the application of a well-established consensus methodology (modified Delphi) to
      rate the appropriateness of imaging and treatment procedures by the panel. In
      those instances in which evidence is lacking or not definitive, expert opinion
      may be used to recommend imaging or treatment.

PMID- 21962783
TI  - White paper from the ACR Task Force on Print Media in Radiology.
AB  - The rapidly changing technological and business environment in which scientific
      journals are published will necessitate ongoing reassessment of operations,
      goals, and priorities. In this white paper, the ACR Task Force on Print Media in
      Radiology reviews the history and role of print media in radiology; discusses
      current and anticipated societal, technological, and financial challenges; and
      explores a variety of strategies to help ensure the relevance of professional
      society publishing in the future.

PMID- 21962784
TI  - Addenda to the radiology report: what are we trying to convey?
AB  - PURPOSE: The aims of this paper are to describe addenda to radiology reports and
      to discuss the communication gaps in radiology addenda reaching referring
      physicians. The authors examine impediments to compliance with an addendum policy
      and suggest possible solutions. METHODS: A total of 62,500 radiology reports were
      reviewed to analyze the occurrence of report addenda. Addenda types were
      separated into clinical, generated by radiologists, and administrative (for
      billing or regulatory reasons). Two radiologists reviewed all clinical addenda
      and classified them as significant or not significant. Significant addenda were
      further analyzed for various aspects. An e-mail survey was also conducted to
      assess prevailing practices in academic departments of radiology. RESULTS: There
      were 1,069 reports with addenda (1.7%). Of these, 575 were generated by
      radiologists. Forty-nine (8.5%) were for clinically significant errors and 526
      (91.5%) were not. Of the 49 significant addenda, 9 (18%) were fully compliant
      with departmental addendum policies, 27 (55%) were noncompliant, and 13 (27%)
      were partially compliant. Of the 49 clinically significant addenda, 17 (55%) were
      dictated within 1 hour and 40 (82%) within 24 hours of the finalized original
      reports. CONCLUSIONS: Poor compliance with an addendum policy was found. The
      reasons for noncompliance and possible remedies are discussed, with the hope of
      beginning a dialogue in the radiology literature on the risks of poor
      communication processes and the benefits of full implementation of well thought
      out addendum policies.

PMID- 21962785
TI  - Trends in utilization rates of the various imaging modalities in emergency
      departments: nationwide Medicare data from 2000 to 2008.
AB  - PURPOSE: To study utilization trends in the various imaging modalities in
      emergency departments (EDs) over a recent multiyear period. METHODS: The
      nationwide Medicare Part B databases for 2000 to 2008 were queried. Medicare's
      location codes were used to identify imaging examinations done on ED patients.
      All diagnostic imaging Current Procedural Terminology((r)) codes were grouped by
      modality. For each code, the database provides procedure volume; utilization
      rates per 1,000 beneficiaries were then calculated. Medicare's physician
      specialty codes were used to determine provider specialty. Utilization trends
      were studied between 2000 and 2008. RESULTS: The overall utilization rate per
      1,000 beneficiaries for all imaging in EDs increased from 281.0 in 2000 to 450.4
      in 2008 (+60%). The radiography utilization rate rose from 227.3 in 2000 to 294.3
      in 2008 (+29%, 67 accrued new studies per 1,000). The CT rate rose from 40.0 in
      2000 to 130.7 in 2008 (+227%, 90.7 accrued new studies per 1,000). The ultrasound
      rate rose from 9.6 in 2000 to 18.7 in 2008 (+95%, 9.1 accrued new studies per
      1,000). Other modalities had much lower utilization. In 2000, CT constituted 14%
      of all ED imaging, but by 2008, it constituted 29%. In 2008, radiologists
      performed 96% of all ED imaging examinations. CONCLUSIONS: The rate of
      utilization of imaging is increasing in EDs. Growth is by far the most pronounced
      in CT, in terms of both the growth rate itself and the actual number of accrued
      new studies per 1,000 beneficiaries. Radiologists strongly predominate as the
      physicians of record for all ED imaging.

PMID- 21962786
TI  - Introducing medical students to radiology as paid emergency department triage
      assistants.
AB  - PURPOSE: The aim of this report is to provide a detailed description of a program
      employing medical students to assist with triaging off-hour diagnostic imaging
      studies at a major academic medical center. METHODS: Current and former
      participants of the Medical student Emergency Department (ED) Radiology Triage
      Program were interviewed regarding the inception, development, and impact of this
      program. Student participation and triage activities were compiled and tabulated
      from scheduling records and triage assistant call logs. RESULTS: Opportunities
      for medical students to obtain an intensive, well-organized experience in
      radiology are often absent or occur relatively late during medical school, which
      can be problematic for developing basic imaging literacy and for making timely,
      well-informed decisions regarding radiology as a career path. The authors
      describe a program that provides students with a rigorous, hands-on experience in
      radiology relatively early in their training by employing medical students to
      assist the emergency department radiology staff with managing off-hour radiology
      workflow. Students work with the off-hour emergency department radiologists and
      staff members answering phone calls and help to facilitate the ordering and
      protocoling of studies and the dissemination of results to clinicians.
      CONCLUSIONS: The employment of medical student triage assistants provides in
      depth exposure to clinical radiology relatively early in medical school, while
      providing an effective system to help streamline the off-hour workflow for
      attending radiologists, residents, technicians, and support staff members.

PMID- 21962787
TI  - Variability in study withdrawal rates among academic neuroradiologists
      participating in a radiology utilization management program.
AB  - PURPOSE: The aim of this study was to analyze variability in study withdrawal
      rates among academic neuroradiologists participating in a utilization management
      (UM) program. METHODS: The activities of 5 academic neuroradiologists
      participating in a UM program were assessed. The project period spanned 42
      months. Participating neuroradiologists received identical training and used
      identical rule sets to evaluate the appropriateness of outpatient CT and MRI
      studies. Neuroradiologists could approve studies on the basis of available
      electronic data or contact referring physicians for further information. The rate
      of withdrawals (defined as "study not performed by consensus" or "study changed
      by consensus" with the referring physician) was compared among the
      neuroradiologists. RESULTS: A total of 5,256 studies were reviewed (mean, 1,051;
      median, 1,043). There were 573 studies (10.9%) not performed by consensus and 298
      studies (5.7%) changed by consensus, resulting in a total of 871 withdrawals
      (16.6%). Among the neuroradiologists, withdrawal rates varied by approximately a
      factor of 2 (mean, 16.5%; median, 15.2%; range, 12.8%-23.5%). Although rate of
      studies not performed by consensus varied by approximately a factor of 2 (mean,
      10.8%; median, 8.1%; range, 7.6%-18.0%), the rate of studies changed by consensus
      showed little variation (mean, 5.7%; median, 5.5%; range, 4.8%-6.6%).
      CONCLUSIONS: Variability in withdrawal rates was related to cases in which
      referring physicians were asked not to perform studies; there was little
      variation when referring physicians were asked to change studies. These data
      imply agreement among the neuroradiologists regarding appropriateness of rule
      sets but suggest that personality characteristics such as persuasiveness,
      persistence, and desire for conflict avoidance may play an important role in
      outcomes.

PMID- 21962788
TI  - Medical imaging data reconciliation, part 2: clinical order entry and imaging
      report data reconciliation.
AB  - Data reconciliation in medical imaging is designed to ensure the accuracy and
      integrity of data across multiple steps in the imaging cycle, ultimately leading
      to improved continuity of patient care. An integral component of this data
      reconciliation is tied to the steps of clinical order entry and radiology report
      creation. The clinical data presented at order entry by the referring clinician
      influence a number of important imaging decisions, including examination
      selection, protocol design, image acquisition and processing, and interpretation
      of the imaging data set. The subsequent data derived from the radiology report
      have a profound impact on diagnosis, treatment, and overall clinical management.
      As a result, the reconciliation of clinical order entry and radiology report data
      affect health care delivery and in many respects are dependent on each other for
      optimal outcomes. The creation of a standardized reconciliation database that
      proactively records, tracks, analyzes, and provides feedback to radiologists and
      clinicians offers the potential to improve the quality and efficiency of patient
      care, while providing objective accountability measures for individual and
      institutional health care providers.

PMID- 21962789
TI  - Learning from high-reliability organizations.

PMID- 21962790
TI  - Faculty attestation statements for resident-generated radiology reports.

PMID- 21962791
TI  - Pointers for optimizing radiation dose in abdominal CT protocols.

PMID- 21962792
TI  - Improving membership retention rates among new graduates.

PMID- 21962793
TI  - Lawrie B. Morrison.

PMID- 21962794
TI  - Autoimmunity in neuromyelitis optica and opticospinal multiple sclerosis:
      astrocytopathy as a common denominator in demyelinating disorders.
AB  - Neuromyelitis optica (NMO) selectively affects the optic nerves and spinal cord.
      In Asians, multiple sclerosis (MS) is rare; however, when it appears, the
      selective and severe involvement of the optic nerves and spinal cord is
      characteristic. This form, termed opticospinal multiple sclerosis (OSMS), has
      similar features to the relapsing form of NMO in Westerners. The discovery that
      NMO-IgG, an NMO-specific IgG, targets aquaporin-4 (AQP4), suggested that NMO is a
      distinct disease entity with a fundamentally different etiology from MS. Because
      NMO-IgG is present in 30-60% of OSMS patients, OSMS in Asians is suggested to be
      the same entity as NMO. Pathologically, perivascular immune complex (IgM, IgG and
      C9neo) deposition and extensive loss of AQP4 in active lesions are reported
      hallmarks of NMO. However, we found that some autopsied NMO cases showed
      selective AQP4 loss while others showed preservation of AQP4, despite extensive
      tissue destruction. Vasculocentric deposition of complement and immunoglobulin
      was detected only in NMO patients, with less than 30% of actively demyelinating
      lesions showing AQP4 loss. Such heterogeneity of AQP4 expression and
      immunoglobulin deposition suggests a heterogeneous disease process in NMO. We
      recently reported that AQP4 was extensively lost in glial fibrillary acidic
      protein-positive hypertrophic astrocytes, both in demyelinated and myelinated
      layers of actively demyelinating lesions in Balo's disease, a variant of MS. We
      also found that in some acute MS lesions, AQP4 was lost extensively far beyond
      the areas of myelin loss. Active demyelinating lesions involved perivascular
      lymphocyte cuffings, consisting mainly of T cells in Balo's disease and MS, while
      the same was true for approximately half of the active lesions in NMO. This
      review proposes that anti-AQP4 antibody-dependent AQP4 loss occurs in some NMO
      patients while antibody-independent AQP4 astrocytopathy can occur in
      heterogeneous demyelinating conditions, including Balo's disease, NMO and MS. The
      latter may be mediated by T cells and other cell-mediated mechanisms, and should
      be tested in future experimental studies.

PMID- 21962795
TI  - Clinical and pathological effects of intrathecal injection of mesenchymal stem
      cell-derived neural progenitors in an experimental model of multiple sclerosis.
AB  - Multiple sclerosis (MS) is associated with irreversible disability in a
      significant proportion of patients. At present, there is no treatment to halt or
      reverse the progression of established disability. In an effort to develop cell
      therapy-based strategies for progressive MS, we investigated the pre-clinical
      efficacy of bone marrow mesenchymal stem cell-derived neural progenitors (MSC
      NPs) as an autologous source of stem cells. MSC-NPs consist of a subpopulation of
      bone marrow MSCs with neural progenitor and immunoregulatory properties, and a
      reduced capacity for mesodermal differentiation, suggesting that this cell
      population may be appropriate for clinical application in the CNS. We
      investigated whether MSC-NPs could promote repair and recovery after intrathecal
      injection into mice with EAE. Multiple injections of MSC-NPs starting at the
      onset of the chronic phase of disease improved neurological function compared to
      controls, whereas a single injection had no effect on disease scores. Intrathecal
      injection of MSC-NPs correlated with reduced immune cell infiltration, reduced
      area of demyelination, and increased number of endogenous nestin-positive
      progenitor cells in EAE mice. These observations suggest that MSC-NPs may
      influence the rate of repair through effects on endogenous progenitors in the
      spinal cord. This study supports the use of autologous MSC-NPs in MS patients as
      a means of promoting CNS repair.

PMID- 21962797
TI  - The allergic paradox: a key to progress in primary prevention of asthma.

PMID- 21962798
TI  - Subcutaneous immunotherapy.

PMID- 21962799
TI  - Immediate breast reconstruction using autologous skin graft associated with
      breast implant.
AB  - BACKGROUND: Immediate breast reconstruction with skin graft is still little
      mentioned in the literature. Follow-up studies regarding the technique aspects
      are particularly scarce. The objective was to detail immediate breast
      reconstruction using autologous skin graft. METHODS: Patients (n = 49) who
      underwent mastectomies and autologous immediate breast reconstruction with skin
      graft associated with a breast implant at A. C. Camargo Hospital (Sao Paulo,
      Brazil) between January 2007 and July 2010 were included. Information on clinical
      data, technique details and clinical outcome were prospectively collected.
      Following mastectomy, the autologous full-thickness skin graft was obtained
      through an inframammary fold incision along the contralateral breast in most
      patients. The skin graft was placed on the surface of the pectoralis major muscle
      after adjustments to conform to the mastectomy defect. A minimum of 10-month
      follow-up period was established. RESULTS: Patients' age ranged from 35 to 55
      years and all received a silicone gel textured surface implant to obtain the
      necessary breast mound. The mean surgical time was 45 min, and the mean amount of
      skin resection was 4.5 cm in the largest diameter. Follow-up ranged from 10 to 35
      months (median 23). All patients had silicone-gel textured surface implants to
      perform the breast mound reconstruction. No complications were observed in 87.8%
      of reconstructions. Forty-six patients (94%) had no complaints about the donor
      site aesthetics. The result was a breast mound with a central ellipse of healed
      skin graft. Three (6%) poor results were observed. Thirty-six patients (67%)
      reported the results as good or very good. CONCLUSIONS: Our results lead us to
      conclude that autologous skin graft provided a reliable option in immediate
      breast reconstruction to skin-sparing mastectomy defects. The technique
      accomplished a single-stage implant breast reconstruction when there is
      inadequate skin coverage.

PMID- 21962800
TI  - Diagnostic performance of iodine-123-metaiodobenzylguanidine scintigraphy in
      differential diagnosis between Parkinson's disease and multiple-system atrophy: a
      systematic review and a meta-analysis.
AB  - BACKGROUND AND PURPOSE: This study was designed to review the diagnostic
      performance of iodine-123-metaiodobenzylguanidine (MIBG) scintigraphy in
      differential diagnosis between Parkinson's disease (PD) and multiple-system
      atrophy (MSA). METHODS: A comprehensive computer literature search of studies
      published through March 2011 regarding MIBG scintigraphy in patients with PD and
      MSA was performed in PubMed/MEDLINE and Embase databases. Only studies in which
      MIBG scintigraphy was performed for differential diagnosis between PD and MSA
      were selected. Pooled sensitivity and specificity of MIBG scintigraphy were
      presented with a 95% confidence interval (CI). The area under the ROC curve was
      calculated to measure the accuracy of MIBG scintigraphy in differential diagnosis
      between PD and MSA. RESULTS: Ultimately, we identified 12 studies comprising a
      total of 1226 patients (593 patients with PD, 117 patients with other Lewy body
      disease, 129 patients with MSA, and 387 patients with other diseases). The pooled
      sensitivity of MIBG scintigraphy to detect PD was 89% (95% CI: 86-91%); the
      pooled specificity of MIBG scintigraphy to discriminate between PD and MSA was
      77% (95% CI: 68-84%). The area under the ROC curve was 0.93. CONCLUSIONS: MIBG
      scintigraphy is an accurate test for PD detection and differential diagnosis
      between PD and MSA; this method shows high sensitivity and adequate specificity
      in this field. Nevertheless, possible causes of false negative and false positive
      findings should be considered when interpreting the scintigraphic results.

PMID- 21962801
TI  - Presentations of acute coronary syndrome related to coronary lesion morphologies
      as assessed by intravascular ultrasound and optical coherence tomography.
AB  - BACKGROUND: Pathologically, the lesions responsible for acute coronary syndrome
      (ACS) are ruptures of vulnerable plaques (and occasionally fibrous-cap erosions
      or calcified nodules) with a superimposed thrombosis. We aimed to clarify the
      clinical presentations related to the morphologies of coronary lesions of ACS
      using intravascular ultrasound (IVUS) and optical coherence tomography (OCT).
      METHODS AND RESULTS: Seventy-five culprit lesions of ACS patients were clearly
      assessed with IVUS and OCT. Patients were classified into two groups based on the
      presence or absence of a rupture of a culprit plaque as identified by OCT.
      Clinical characteristics and lesion morphologies were compared between the two
      groups. Waist circumference was significantly greater (p<0.02) and prevalence of
      the metabolic syndrome (MS) higher (p=0.0011) in the rupture group. The
      prevalence of prodromal angina was higher in patients without plaque ruptures
      (p<0.0001). Using multivariate analysis, the MS and prodromal angina were
      independent predictors of rupture of a culprit coronary plaque (odds ratio (OR):
      27.30, p<0.003 and OR: 0.04, p=0.0004, respectively). Among the components of the
      MS, the prevalence of abdominal obesity was a significant independent predictor
      of rupture of a culprit plaque (OR: 4.24, p<0.02). CONCLUSIONS: There are two
      presentations related to the coronary lesion morphologies of ACS: we should
      understand these aspects of ACS.

PMID- 21962802
TI  - Cardioprotective activity of Amaranthus viridis Linn: effect on serum marker
      enzymes, cardiac troponin and antioxidant system in experimental myocardial
      infarcted rats.
AB  - BACKGROUND: Cardiovascular diseases (CVDs) have a high prevalence in developing
      and developed countries and myocardial infarction accounts for majority of deaths
      and disabilities. The current study dealt with the protective role of Amaranthus
      viridis Linn on isoproterenol (ISO)-induced myocardial infarction (MI) in rats.
      METHODS: Subcutaneous injection of ISO (20 mg/kg body weight in 1 ml saline) to
      rats for two consecutive days offered significant alteration in cardiac marker
      enzymes (AST, ALT, LDH and CPK), cardiac troponin, lipid peroxidation products
      (TBARS and hydroperoxide) and antioxidant system (CAT, SOD, GPx, GST, GSH and
      GSSG). ISO-induced myocardial damage was indicated by increased activities of
      marker enzymes in serum and the levels of cardiac troponin in the serum. In
      addition to these diagnostic markers, the levels of lipid peroxidation products
      in the heart were significantly (p<0.05) increased and the activities of enzymic
      antioxidants and non-enzymic antioxidant such as glutathione in the heart was
      significantly (p<0.05) decreased and GSSG in the heart was increased in ISO
      induced rats. RESULTS: Effect of Amaranthus viridis oral treatment (100, 200 and
      300 mg/kg body weight) for 45 days elicited a significant cardio protective
      activity by lowering the levels of serum marker enzymes, cardiac troponin, GSSG
      and lipid peroxidation and elevated the levels of antioxidant enzymes and GSH.
      The effect at a dose of 300 mg/kg of A. viridis was more pronounced than that of
      the dose 100 mg/kg and 200mg/kg and brought back all the parameters to near
      normal. The effect produced by A. viridis was compared with alpha-tocopherol.
      CONCLUSIONS: The present findings have demonstrated that the cardioprotective
      effects of A. viridis in ISO-induced oxidative damage may be due to an
      augmentation of the endogenous antioxidants and inhibition of lipid peroxidation
      of membrane.

PMID- 21962803
TI  - The role of osteopontin and osteopontin aptamer (OPN-R3) in fibroblast activity.
AB  - BACKGROUND: Scarring is believed to be caused by both persistent inflammation and
      overexuberant fibroblast activation. Osteopontin (OPN) is a cytokine that
      promotes cell activation. The absence of OPN in vivo reduces dermal scarring.
      This suggests that OPN is involved in scar formation; however, how OPN exerts
      these pro-scarring effects is unknown. RNA aptamers are short RNA molecules that
      bind target proteins with high affinity. The aptamer OPN-R3 (R3) blocks OPN
      signaling. The role of R3 in preventing dermal fibrosis is unknown. METHODS:
      Fibroblast migration was analyzed with the use of Boyden Chambers and HEMA-3
      staining. Inverted confocal microscopy was used to assess fibroblast focal
      adhesion length. Adhesion was measured by incubating fluorescently stained
      fibroblasts on OPN coated 96-well plates. CellTiter 96 AQueous non-radioactive
      cell proliferation assay was utilized to investigate the proliferative activity
      of fibroblasts. Free floating collagen lattices were utilized to assess
      fibroblast contractility. RESULTS: Human dermal fibroblasts migrated
      significantly in response to OPN. OPN did not induce a significant increase in
      focal adhesion length compared with controls. Adhesion studies demonstrated that
      OPN increased fibroblast adhesion. Proliferation assays indicate that OPN
      increased fibroblast growth. OPN increased fibroblast contractility of collagen
      lattices. The addition of R3 significantly inhibited OPN-induced activity.
      CONCLUSION: OPN is associated with scar and exerts pro-scarring effects by
      increasing cellular migration, adhesion, proliferation, and contractility of
      human dermal fibroblasts. R3 prevents OPN mediated activity. OPN may be useful
      for promoting closure of non-healing wounds and the OPN specific aptamer, R3, may
      be useful for preventing fibrosis.

PMID- 21962804
TI  - Effects of pioglitazone on survival and omental adipocyte function in mice with
      sepsis induced by cecal ligation and puncture.
AB  - BACKGROUND: To examine the effects of pioglitazone, peroxisome proliferator
      activated receptor-gamma (PPAR-gamma), on mortality and omental adipocyte
      function in mice with cecal ligation and puncture (CLP). METHODS: Male mice were
      assigned to receive (1) vehicle/sham-operation, (2) pioglitazone/CLP, or (3)
      vehicle/CLP. Pioglitazone was injected intraperitoneally for 7 d before
      operation. Serum and omental tissue were collected before, 24, and 48 h after
      CLP. Serum levels of adiponectin, cytokine, and chemokine were measured with
      ELISA. mRNA expressions in omental tissues were determined by RT-PCR. Survival
      was monitored for 7 d after CLP. RESULTS: Survival after CLP was significantly
      better in the pioglitazone/CLP than in the vehicle/CLP. Serum adiponectin levels
      before CLP were higher in the pioglitazone/CLP than in the vehicle/CLP. Treatment
      with pioglitazone significantly inhibited the increases in the serum interleukin
      6 and monocyte chemoattractant protein-1 (MCP-1) levels after CLP and lowered the
      mRNA expressions of proinflammatory cytokines, interleukin-6, and MCP-1 in
      omental tissue after CLP. CONCLUSION: The anti-inflammatory effects of
      pioglitazone on omental adipocyte function appear to be mediated in part by PPAR
      gamma activation, which down-regulates the production of inflammatory mediators.

PMID- 21962805
TI  - The aqueous extract of Angelica sinensis, a popular Chinese herb, inhibits wear
      debris-induced inflammatory osteolysis in mice.
AB  - BACKGROUND: More and more studies have shown Angelica sinensis' (AS) therapeutic
      action on chronic inflammatory diseases in recent years. We investigated effects
      of aqueous extract of AS on inflammatory cytokines release and wear debris
      particles-induced osteolysis. MATERIALS AND METHODS: Ultra high molecular weight
      polyethylene (UHMWPE) particles were used to induce inflammation in RAW264.7 cell
      and C57BL/J6 mice. AS extract was obtained through a series of purification
      steps, and divided into high dose group and low dose group during the research of
      cell culture, tissue culture, and animal treatment. After 72 h culture with
      optimal particles, supernatants were collected for cytokine analysis. Calvaria
      were harvested from the mice model after 10 d treatment with the AS extract. Six
      calvaria of each group were cultured into medium for 72 h for analyzing cytokine
      generated in vivo. Histologic analyses and micro-computed tomography (micro-CT)
      scan were used to determine osteoclastogenesis and inflammatory bone resorption.
      RESULTS: Concentration of tumor necrosis-alpha (TNF-alpha) and interleukin-1beta
      (IL-1beta) was significantly attenuated by AS extract both in vitro and in vivo.
      The osteolysis area and the osteoclast numbers were decreased from 0.406 +/-
      0.0799 to 0.117 +/- 0.0103 mm(2), and from 22.7 +/- 5.0 to 11.3 +/- 1.8,
      respectively (P < 0.01). Compared with the control group, the protection effects
      of AS extract was further confirmed with data of the more accurate 3-dimension
      micro-CT reconstruction. CONCLUSIONS: This study suggests a potential resolution
      of inhibiting wear debris particles-induced inflammatory bone resorption, as well
      as a possible way of inhibiting aseptic loosening after joint replacement
      surgery.

PMID- 21962806
TI  - Efficacy and safety of iron supplementation for the elderly patients undergoing
      hip or knee surgery: a meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Anemia is a frequent co-morbidity in the elderly patients undergoing
      hip or knee surgery and is often associated with poor clinical outcomes. Mild to
      moderate anemia is often treated with intravenous or oral iron supplementation.
      However, the efficacy and safety of iron supplementation in treating anemia for
      the elderly patients undergoing hip or knee surgery remains controversial.
      METHODS: Only prospective, randomized studies that compared iron supplementation
      with no iron supplementation in the elderly patients undergoing hip or knee
      surgery were included. Six studies met the inclusion criteria: the target
      population consisted of patients undergoing hip or knee surgery treated with iron
      supplementation; the study was a published randomized trial. Each outcome measure
      tested was assessed for heterogeneity. If significant heterogeneity was present
      for more than 75%, data from the studies were not combined. If there was no
      significant heterogeneity (less than 40%), a weighted mean difference (WMD) or
      combined relative risk was calculated using a fixed effects model, while a random
      effects model was applied when heterogeneity was within 40% to 75%. RESULTS: Our
      meta-analysis demonstrated the increase of hemoglobin level in patients
      undergoing hip or knee surgery with iron supplementation. However, no significant
      difference on the length of hospital stay, morbidity, 1-mo mortality, the
      infection rate, the rate and volume of allogeneic blood transfusions, and the
      adverse drug effects was found between the patients with iron treatment and those
      without. CONCLUSION: Our meta-analysis suggested that iron supplementation was
      safe and effective in treating anemia for the elderly patients undergoing hip or
      knee surgery.

PMID- 21962807
TI  - Pretreatment of Rho kinase inhibitor inhibits systemic inflammation and prevents
      endotoxin-induced acute lung injury in mice.
AB  - BACKGROUND: Systemic inflammatory mediators play an important role in the
      development of sepsis. In this study, we analyzed the role of Rho kinase in the
      activation of immune response and acute lung injury in a mouse model of sepsis.
      METHODS: C57BL/6J mice were randomly divided into three groups: control, LPS, and
      LPS+fasudil. We used a mouse model of endotoxemia that consists of
      intraperitoneal injection of a high dose of LPS (30 mg/kg); a Rho kinase
      inhibitor, fasudil (10 mg/kg), dissolved in sterile saline (1 MUL/g body weight)
      was applied by intraperitoneal injection at 18 and 1 h before injection of LPS
      (LPS+fasudil group). The control mice received vehicle sterile saline only. Blood
      was collected and lungs were harvested at 3 and/or 6 h for analysis. RESULTS: At
      3 and 6 h, the increased TNF-alpha and IL-1beta levels in plasma and MPO activity
      in lung tissue by LPS could be significantly inhibited by fasudil. In addition,
      LPS-induced histologic changes in the lungs at 6 h could be effectively reversed
      by fasudil pretreatment. Furthermore, pretreatment of mice with fasudil inhibited
      LPS-induced increasing of TNF-alpha, IL-1beta mRNA expression (3 and 6 h) and AP
      1/DNA binding activity (3 h) in blood cells. In survival studies, fasudil (10
      mg/kg), which was administered 18 and 1 h before the application of LPS,
      conferred a protection against lethality induced by LPS (30 mg/kg). CONCLUSION:
      These results suggest that Rho kinase may play a role in the pathology of
      systemic inflammation during early phase of sepsis, and the potential mechanism
      of action may be partly through the adjustment of AP-1 pathway.

PMID- 21962808
TI  - Modulating the inflammatory response in sepsis.

PMID- 21962809
TI  - Suppressive effects of interleukin-18 on liver function in rat liver allografts.
AB  - BACKGROUND: Interleukin-18 (IL-18) is a potent proinflammatory cytokine that
      augments both innate and acquired immune responses. It is also a crucial
      regulator of lymphocyte production of interferon-gamma (IFN-gamma), which can
      promote acute cellular rejection of transplanted solid organs. METHODS: To
      evaluate the role of IL-18 in liver transplantation, we constructed an adenoviral
      vector encoding IL-18 binding protein (Adex-IL18bp), which specifically
      suppressed the biologic activity of IL-18, and examined the effect of this
      suppression on liver allografts by using a high-responder rat model (ACI to
      Lewis) of orthotopic liver transplantation (OLTx). Donor rats were given one
      intravenous injection of Adex-IL18bp or Adex-LacZ (control vector) 2 d before
      OLTx. RESULTS: Seven days after OLTx, overexpression of IL-18bp resulting from
      the adenovirus gene transfer was associated with significantly decreased serum
      alanine aminotransferase levels and less histologic hepatic injury in recipient
      rats with Adex-IL18bp-pretreated donors compared with Adex-LacZ controls. Adex
      IL18bp pretreatment also significantly prolonged rat/allograft survival,
      inhibited expression of IFN-gamma, and reduced levels (versus control values) of
      both CXCL10 and CX3CL1, which can be induced by IFN-gamma. CONCLUSION: These
      results suggest that IL-18 has an important role in liver allograft rejection
      through IFN-gamma and chemokines and that specific suppression of IL-18 may
      improve liver function early after transplantation.

PMID- 21962810
TI  - Gene targeting and cloning in pigs using fetal liver derived cells.
AB  - BACKGROUND: Since there are no pig embryonic stem cells, pig genetic engineering
      is done in fetal fibroblasts that remain totipotent for only 3 to 5 wk. Nuclear
      donor cells that remain totipotent for longer periods of time would facilitate
      complicated genetic engineering in pigs. The goal of this study was to test the
      feasibility of using fetal liver-derived cells (FLDC) to perform gene targeting,
      and create a genetic knockout pig. MATERIALS AND METHODS: FLDC were isolated and
      processed using a human liver stem cell protocol. Single copy alpha-1,3
      galactosyl transferase knockout (GTKO) FLDCs were created using electroporation
      and neomycin resistant colonies were screened using PCR. Homozygous GTKO cells
      were created through loss of heterozygosity mutations in single GTKO FLDCs.
      Double GTKO FLDCs were used in somatic cell nuclear transfer (SCNT) to create
      GTKO pigs. RESULTS: FLDCs grew for more than 80 population doublings, maintaining
      normal karyotype. Gene targeting and loss of heterozygosity mutations produced
      homozygous GTKO FLDCs. FLDCs used in SCNT gave rise to homozygous GTKO pigs.
      CONCLUSIONS: FDLCs can be used in gene targeting and SCNT to produce genetically
      modified pigs. The increased life span in culture compared to fetal fibroblasts
      may facilitate genetic engineering in the pig.

PMID- 21962811
TI  - Review of various techniques of small bowel transplantation in pigs.
AB  - Because of anatomical and physiological similarities to humans, porcine small
      bowel transplantation (SBTx) can be used as an appropriate experimental model in
      the field of surgical research. Various approaches to SBTx have been described in
      literature. The aim of this work is to present a review of different surgical
      techniques of SBTx which have been developed using the porcine model. Our
      analysis of Medline-cited studies dealing with different techniques of SBTx in
      porcine models was particularly focused on surgical aspects. With regard to graft
      procurement and enterectomy, the reported techniques vary widely. Arterial
      reconstruction is mainly conducted by performing the anastomosis between the
      superior mesenteric artery (SMA) of the donor and SMA or infrarenal aorta of the
      recipient. Alternatively, an aortic segment of the donor can be anastomosed to
      the infrarenal aorta of the recipient. Venous anastomosis is frequently performed
      between the superior mesenteric vein (SMV) of the donor and SMV or the inferior
      vena cava (IVC) of the recipient. Some studies also report venous anastomosis
      between the portal vein of the donor and the recipient. Bowel continuity is then
      restored by end-to-end or end-to-side anastomosis. Remarkable results were
      generated thanks to improved techniques which include proximal side-to-side ileo
      ileal anastomosis with double-barrel ileostomy, or so-called "Paul-Mikulicz
      Ileostomy". Most frequently used were jejunostomy and the "Bishop-Koop-Ileostomy"
      -where the proximal part of the bowel is anastomosed end-to-side to the distal
      part, which is then exteriorized as an ostomy. Based on the techniques presented
      in this review, one must select the most suitable surgical technique of porcine
      SBTx among those various models.

PMID- 21962812
TI  - Commentary on "early myocardial dysfunction is not caused by mitochondrial
      abnormalities in a rat model of peritonitis".

PMID- 21962814
TI  - Commentary on "Treatment of tourniquet-induced ischemia reperfusion injury with
      muscle progenitor cells".

PMID- 21962813
TI  - Splenectomy increases atherosclerotic lesions in apolipoprotein E deficient mice.
AB  - BACKGROUND: Atherosclerosis is an inflammatory immune disease associated with
      lipid accumulation in the intima layer of arteries. The spleen plays an important
      immune function, but its influence in development of atherosclerosis remains
      unclear. Evaluation of the role of the spleen in atherosclerosis is justified due
      to the high frequency of total splenectomies. In this work, the effect of
      splenectomy on the development of atherosclerosis in apolipoprotein E (ApoE)
      deficient mice was investigated. METHODS: ApoE deficient mice were divided into a
      sham-operated control group (CT) and a splenectomized group (SP). Thirty days
      after surgery, animals were fed a high fat western diet. After 8 wk, mice were
      euthanized and their blood, heart, and aorta were subjected to analysis.
      Atherosclerotic lesion areas in the aortic root were stained with hematoxylin
      eosin and quantified by morphometry. The atherosclerotic lesions in the thoracic
      and abdominal portions of aorta were determined by assessing the percentage of
      the luminal surface area stained by Sudan IV. Total serum cholesterol and anti
      oxidized LDL antibodies were measured. RESULTS: Levels of total serum cholesterol
      did not vary significantly after splenectomy. Anti-oxidized LDL IgG antibodies
      were similar between groups. However, compared with the control group, lesions in
      the aortic root were significantly larger in splenectomized mice (P<0.01). These
      data were confirmed by the increase of atherosclerotic area in the thoracic and
      abdominal portions of aorta in splenectomized mice. CONCLUSIONS: These data
      indicate that splenectomy increases atherosclerotic lesions in ApoE deficient
      mice fed an atherogenic diet, suggesting an atheroprotector role of the spleen.

PMID- 21962815
TI  - Economics of appendicitis: cost trend analysis of laparoscopic versus open
      appendectomy from 1998 to 2008.
AB  - BACKGROUND: Laparoscopic appendectomy (LA) has become more acceptable for the
      treatment of appendicitis over the last decade; however, its cost benefit
      compared to open appendectomy (OA) remains under debate. The purpose of this
      study is to evaluate the utilization of LA and its cost effectiveness based on
      total hospital charges stratified by complexity of disease and complications
      compared to OA. MATERIAL AND METHODS: Nationwide Inpatient Sample data from 1998
      to 2008 with the principal diagnosis of appendicitis were included. Appendicitis
      cases were divided by simple and complex (peritonitis or abscess) and subdivided
      by OA, LA, and lap converted to open (CONV). Total charges (2008 value), length
      of stay (LOS), and complications were assessed by disease presentation and
      operative approach. RESULTS: Between 1998 and 2008, 1,561,518 (54.3%) OA,
      1,231,643 (42.8%) LA, and 84,662 (2.9%) CONV appendectomies were performed. LA
      had shorter LOS (2 d) than OA (3 d) and CONV (5 d) (P<0.001). CONV (7.4%) cases
      had more complications than OA (3.7%) and LA (2.6%). LA ($19,978) and CONV
      ($28,103) are costlier than OA ($15,714) based on normalized cost for simple and
      complex diseases (P<0.001). CONCLUSIONS: LA is more prevalent but its cost is
      higher in both simple and complex cases. Cost and complications increase if the
      case is converted to open. OA remains the most cost effective approach for
      patients with acute appendicitis.

PMID- 21962817
TI  - The renal protective effect of erythropoietin on acute ischemic injury in kidney
      transplantation.

PMID- 21962816
TI  - Role for Gbetagamma G-proteins in protease regulation during remodeling of the
      murine femoral artery.
AB  - BACKGROUND: Intimal hyperplasia remains the principal lesion in the development
      of restenosis after vessel wall injury. G-protein coupled receptors are involved
      in smooth muscle cell proliferation but the role of Gbetagamma in arterial
      intimal hyperplasia has not been well defined. The aim of this study is to
      characterize the expression of Gbetagamma G-proteins in the developing intimal
      hyperplasia in a murine model and the impact of disruption of Gbetagamma
      signaling on intimal hyperplasia development. METHODS: The murine femoral wire
      injury model was employed. Specimens were perfusion-fixed and sections were
      stained with H&E and Movat's stains such that morphometry could be performed
      using an Image-Pro system. Additional specimens of femoral artery were also
      harvested and snap frozen for Western blotting for the Gbetagamma expression and
      for Western blotting and zymography to allow for the study of gelatinase and
      plasminogen activator expression and activation. Contralateral vessels were used
      as controls. Additional vessels were immersed in pluronic gel containing an
      adenovirus with the Gbetagamma inhibitor betaARK(CT). RESULTS: The injured
      femoral arteries developed intimal hyperplasia, while sham vessels did not
      produce such a response. Cell proliferation peaked at 3-5 d and cell migration at
      7 d after injury. There was a marked time-dependent increase in Gbetagamma over
      the 28 d following injury. Inhibition of Gbetagamma with betaARK(CT) inhibited
      cell proliferation, cell migration and the development of intimal hyperplasia.
      Inhibition of Gbetagamma decreased peak uPA activity and expression without
      increasing early PAI-1 activity and expression. Inhibition of Gbetagamma reduced
      peak MMP-2 activity at d 1 but not at d 7 and also reduced peak MMP-9 activity at
      d 3. Protein expression for both MMP-2 and MMP-9 was also transiently decreased.
      There were no changes in TIMP-1 and TIMP-2 expression and activity. CONCLUSIONS:
      These data demonstrate a time-dependent increase in Gbetagamma G-protein
      expression following wire injury in the mouse. Inhibition of Gbetagamma alters
      cell proliferation and migration with associated changes in MMP-2, MMP-9, and uPA
      expression and activity.

PMID- 21962818
TI  - Comparison of the effects of epidural or intravenous methadone on the minimum
      alveolar concentration of isoflurane in dogs.
AB  - The effects of epidural and intravenous (IV) methadone (0.5mg/kg) on the minimum
      alveolar concentration of isoflurane (ISO(MAC)) were compared in dogs. Six dogs
      (16.5 +/- 2.5 kg bodyweight) received three treatments in random order during
      isoflurane anaesthesia, with a 7 day washout interval between each study.
      Methadone was injected via a lumbosacral epidural catheter introduced 10 cm
      cranially into the epidural canal and the electrical stimulation for ISO(MAC)
      determination was applied either to the thoracic (EP(T) treatment) or to the
      pelvic limb (EP(P) treatment) during separate study days. In the IV treatment,
      ISO(MAC) was determined via electrical stimulation of the pelvic limb. Variables
      were recorded before (baseline), 2.5 and 5h after drug injection. The ISO(MAC)
      decreased significantly (P<0.05) from baseline at 2.5 and 5h after methadone in
      all treatments. At 2.5h, the magnitude of ISO(MAC) reduction did not differ
      between treatments (mean decreases from baseline: 30-33%). The ISO(MAC) reduction
      lasted longer following epidural methadone in the thoracic limb (decreases from
      baseline: 30% at 5h in the EP(T) treatment vs. 19% and 16% in the EP(P) and IV
      treatments, respectively). Although the isoflurane sparing effect provided by
      epidural methadone was not significantly greater than IV methadone during the
      initial stage (2.5h), it was more prolonged than the IV route in specific
      dermatomes (5h in the thoracic limb) with the epidural technique employed.
      Methadone may therefore provide a greater isoflurane sparing effect when
      administered epidurally, compared to IV, when noxious stimulation occurs in
      specific dermatomes.

PMID- 21962819
TI  - Physics and technology in ESTRO and in Radiotherapy and Oncology: past, present
      and into the 4th dimension.

PMID- 21962820
TI  - Clinical use of a novel in vivo 4D monitoring system for simultaneous patient
      motion and dose measurements.
AB  - PURPOSE: A new 4D in vivo dosimetry tool, RADPOS, has been used on lung cancer
      patients to evaluate the feasibility of using the detectors to characterize
      variations in patient breathing patterns as well as to monitor daily variations
      in dose. METHODS AND MATERIALS: The RADPOS system combines a MOSFET dosimeter
      with an electromagnetic positioning sensor for simultaneous measurement of real
      time dose and spatial coordinates. Three RADPOS sensors were placed on patients'
      chest and abdomen during a 4DCT and daily treatments. A fourth detector was also
      placed on the couch as reference. Position data were collected in real-time and
      total dose was read at the end of each fraction. RESULTS: Significant deviations
      in surface motion have been found between the day of 4DCT and treatment fractions
      in 9 of 10 patients. Variations in daily dose ranged from 2.5 to 13.7 cGy (2.8
      14.0%) and results agreed with treatment plan values for all but three points.
      CONCLUSIONS: Changes in breathing motion have been found that emphasize a need
      for continued position monitoring. RADPOS measurements can be used to monitor
      such variations as well as to measure surface dose without any disruption to the
      treatment schedule or discomfort to patients.

PMID- 21962821
TI  - A comparison of several modulated radiotherapy techniques for head and neck
      cancer and dosimetric validation of VMAT.
AB  - PURPOSE: Volumetric modulated arc therapy (VMAT) has the potential to shorten
      treatment times for fluence modulated radiotherapy. We compared dose
      distributions of VMAT, step-and-shoot IMRT and serial tomotherapy for typical
      head and neck (H&N) planning target volumes (PTV) with sparing of one parotid, a
      complex paradigm and a situation often encountered in H&N radiotherapy. Finally,
      we validated the dosimetric accuracy of VMAT delivery. MATERIAL AND METHODS:
      Based on CT datasets of 10 patients treated for H&N cancer (PTV1:60 Gy/PTV2:56
      Gy) with IMRT (7/9 fields), serial tomotherapy (MIMiC) and VMAT were compared
      with regard to plan quality and treatment efficiency. Plan quality was assessed
      by calculating homogeneity/conformity index (HI/CI), mean dose to parotid and
      brain stem and the maximum dose to the spinal cord. For plan efficiency
      evaluation, total treatment time (TTT) and number of monitor units (MU) were
      considered. A dosimetric evaluation of VMAT was performed using radiosensitive
      film, ion chamber and 2D-array. RESULTS: For MIMiC/IMRT(7F)/IMRT(9F)/VMAT, mean
      CI was 1.98/2.23/2.23/1.82, HI(PTV1) was 1.12/1.20/1.20/1.11 and HI(PTV2) was
      1.11/1.15/1.13/1.12. Mean doses to the shielded parotid were 19.5 Gy/14.1 Gy/13.9
      Gy/14.9 Gy and the spinal cord received maximum doses of 43.6 Gy/40.8 Gy/41.6
      Gy/42.6 Gy. The mean MU's were 2551/945/925/521 and the mean TTT was 12.8 min/7.6
      min/8.5 min/4.32 min. The ion chamber measurements showed an absolute deviation
      of 0.08 +/- 1.10% and 98.45 +/- 3.25% pixels passed gamma-analyses for 3%/3mm and
      99.95 +/- 0.09% for 5%/5mm for films. 2D-array measurements reported an agreement
      for 3%/3mm of 95.65 +/- 2.47%-98.33 +/- 0.65% and for 5%/5mm 99.79 +/- 0.24%
      99.92 +/- 0.09% depending on the measurement protocol. CONCLUSION: All treatment
      paradigms produced plans of excellent quality and dosimetric accuracy with IMRT
      providing best OAR sparing and VMAT being the most efficient treatment option in
      our comparison of treatment plans with high complexity.

PMID- 21962822
TI  - Performance of an atlas-based autosegmentation software for delineation of target
      volumes for radiotherapy of breast and anorectal cancer.
AB  - BACKGROUND AND PURPOSE: To validate atlas-based autosegmentation for contouring
      breast/anorectal targets. METHODS AND MATERIALS: ABAS uses atlases with defined
      CTVs as template cases to automatically delineate target volumes in other patient
      CT-datasets. Results are compared with manually contoured CTVs of
      breast/anorectal cancer according to RTOG-guidelines. The impact of using
      specific atlases matched to individual patient geometry was evaluated. Results
      were quantified by analyzing Dice Similarity Coefficient (DSC), logit(DSC) and
      Percent Overlap (PO). DSC >0.700 and logit(DSC) >0.847 are acceptable. In
      addition a new algorithm (STAPLE) was evaluated. RESULTS: ABAS produced good
      results for the CTV of breast/anorectal cancer targets. Delineation of inguinal
      lymphatic drainage, however, was insufficient. Results for breast CTV were (DSC:
      0.86-0.91 ([0,1]), logit(DSC): 1.82-2.36 ([-infinity,infinity]), PO: 75.5-82.89%)
      and for anorectal CTVA (DSC: 0.79-0.85, logit(DSC): 1.40-1.77, PO: 68-73.67%).
      CONCLUSIONS: ABAS produced satisfactory results for these clinical target volumes
      that are defined by more complex tissue interface geometry, thus streamlining and
      facilitating the radiotherapy workflow which is essential to face increasing
      demand and limited resources. STAPLE improved contouring outcome. Small target
      volumes not clearly defined are still to be delineated manually. Based on these
      results, ABAS has been clinically introduced for precontouring of CTVs/OARs.

PMID- 21962823
TI  - Dosimetric comparison of helical tomotherapy, RapidArc, and a novel IMRT & Arc
      technique for esophageal carcinoma.
AB  - PURPOSE: To compare radiotherapy treatment plans for mid- and distal-esophageal
      cancer with primary involvement of the gastroesophageal (GE) junction using a
      novel IMRT & Arc technique (IMRT & Arc), helical tomotherapy (HT), and RapidArc
      (RA1 and RA2). METHODS AND MATERIALS: Eight patients treated on HT for locally
      advanced esophageal cancer with radical intent were re-planned for RA and
      IMRT&Arc. RA plans employed single and double arcs (RA1 and RA2, respectively),
      while IMRT&Arc plans had four fixed-gantry IMRT fields and a conformal arc. Dose
      volume histogram statistics, dose uniformity, and dose homogeneity were analyzed
      to compare treatment plans. RESULTS: RA2 plans showed significant improvement
      over RA1 plans in terms of OAR dose and PTV dose uniformity and homogeneity. HT
      plan provided best dose uniformity (p=0.001) and dose homogeneity (p=0.002) to
      planning target volume (PTV), while IMRT&Arc and RA2 plans gave lowest dose to
      lungs among four radiotherapy techniques with acceptable PTV dose coverage. Mean
      V(10) of the lungs was significantly reduced by the RA2 plans compared to
      IMRT&Arc (40.3%, p=0.001) and HT (66.2%, p<0.001) techniques. Mean V(15) of the
      lungs for the RA2 plans also showed significant improvement over the IMRT&Arc
      (25.2%, p=0.042) and HT (34.8%, p=0.027) techniques. These improvements came at
      the cost of higher doses to the heart volume compared to HT and IMRT&Arc
      techniques. Mean lung dose (MLD) for the IMRT&Arc technique (21.2 +/- 5.0% of
      prescription dose) was significantly reduced compared to HT (26.3%, p=0.004), RA1
      (23.3%, p=0.028), and RA2 (23.2%, p=0.017) techniques. CONCLUSION: The IMRT&Arc
      technique is a good option for treating esophageal cancer with thoracic
      involvement. It achieved optimal low dose to the lungs and heart with acceptable
      PTV coverage. HT is a good option for treating esophageal cancer with little
      thoracic involvement as it achieves superior dose conformality and uniformity.
      The RA2 technique provided for improved treatment plans using additional arcs
      with low doses to the lungs at the cost of increased heart dose. Plan quality
      could still be improved through the use of additional arcs.

PMID- 21962824
TI  - Another form of subgroup to beware.

PMID- 21962825
TI  - Diseased skeletal muscle: a noncardiac source of increased circulating
      concentrations of cardiac troponin T.
AB  - OBJECTIVES: The purpose of this study was to determine whether there is
      immunoreactive cardiac troponin T (cTnT) expression in diseased skeletal muscle
      that might cause possible false-positive increases in cTnT. BACKGROUND: Cardiac
      troponin (I or T) is the biomarker of choice for the diagnosis of cardiac injury.
      Recently, we were presented with a case that challenged the specificity of cTnT.
      METHODS: Patients with myopathies seen in the Neuromuscular Clinic at the Mayo
      Clinic were screened for increases in cTnT. If present, an assay for cTnI was
      performed. If normal, skeletal biopsy tissue was obtained for Western blot
      analysis using the capture and detection antibodies from both the fourth
      generation and high-sensitivity cTnT assays. Results were compared with findings
      in normal cardiac tissue. RESULTS: Sixteen patients had increases in cTnT but not
      cTnI. All had a myopathy by clinical evaluation, clinical testing, and biopsy.
      Four residual biopsy samples were obtained. All 3 antibodies used in the cTnT
      (M11.7, M7) and high-sensitivity cTnT (5D8, M7) assays were immunoreactive with a
      37- to 39-kDa protein in all 4 diseased skeletal muscle biopsy specimens and in
      cardiac tissue. A second immunoreactive isoform (34 to 36 kDa) was also found in
      1 patient. None of the noncardiac control tissues expressed immunoreactive
      protein. CONCLUSIONS: These results document that there are forms in diseased
      skeletal muscle that could cause increases in circulating levels of cTnT. These
      increases could reflect re-expressed isoforms. Clinicians need to be aware of the
      possibility that noncardiac increases in cTnT may occur and lead to a possible
      false-positive diagnosis of cardiac injury when skeletal muscle pathology is
      present.

PMID- 21962826
TI  - If the real world were irrelevant, so to speak: The role of propositional truth
      value in counterfactual sentence comprehension.
AB  - Propositional truth-value can be a defining feature of a sentence's relevance to
      the unfolding discourse, and establishing propositional truth-value in context
      can be key to successful interpretation. In the current study, we investigate its
      role in the comprehension of counterfactual conditionals, which describe
      imaginary consequences of hypothetical events, and are thought to require keeping
      in mind both what is true and what is false. Pre-stored real-world knowledge may
      therefore intrude upon and delay counterfactual comprehension, which is predicted
      by some accounts of discourse comprehension, and has been observed during online
      comprehension. The impact of propositional truth-value may thus be delayed in
      counterfactual conditionals, as also claimed for sentences containing other types
      of logical operators (e.g., negation, scalar quantifiers). In an event-related
      potential (ERP) experiment, we investigated the impact of propositional truth
      value when described consequences are both true and predictable given the
      counterfactual premise. False words elicited larger N400 ERPs than true words, in
      negated counterfactual sentences (e.g., "If N.A.S.A. had not developed its Apollo
      Project, the first country to land on the moon would have been Russia/America")
      and real-world sentences (e.g., "Because N.A.S.A. developed its Apollo Project,
      the first country to land on the moon was America/Russia") alike. These
      indistinguishable N400 effects of propositional truth-value, elicited by opposite
      word pairs, argue against disruptions by real-world knowledge during
      counterfactual comprehension, and suggest that incoming words are mapped onto the
      counterfactual context without any delay. Thus, provided a sufficiently
      constraining context, propositional truth-value rapidly impacts ongoing semantic
      processing, be the proposition factual or counterfactual.

PMID- 21962827
TI  - 'Care, and not fine stables, make a good horse': addressing the sustainability
      and welfare of geriatric horses.

PMID- 21962828
TI  - Oxidant-antioxidant imbalance in horses infected with equine infectious anaemia
      virus.
AB  - This study assesses the impact of equine infectious anaemia virus (EIAV)
      infection on the oxidant/antioxidant equilibrium of horses. Blood samples from 96
      Romanian horses aged 1-25 years, were divided into different groups according to
      their EIAV-infection status, age, and time post-seroconversion. The effect of
      infection on oxidative stress was estimated by measuring enzymatic antioxidants
      (superoxide dismutase [SOD], glutathione peroxidase [GPx] and catalase), non
      enzymatic antioxidants (uric acid and carotenoids), and lipid peroxidation
      (malondialdehyde [MDA]). Infection modified the oxidant/antioxidant equilibrium
      in the horses, influencing GPx and uric acid levels (P<0.05). Time post
      seroconversion also contributed to oxidative stress imbalance, exhibiting a
      significant influence on both SOD and MDA concentrations in the blood (P<0.05).
      Animal age did not have a significant influence on oxidative stress. Recently
      infected horses (<1 year following seroconversion), and horses >5 years old,
      represented the most vulnerable category in terms of oxidative stress, followed
      by recently infected animals <5 years old. The results of this study are novel in
      implicating EIAV infection in the development of oxidative stress in horses.

PMID- 21962829
TI  - Apparent prevalence of antibodies to Coxiella burnetii (Q fever) in bulk tank
      milk from dairy herds in southern Belgium.
AB  - In 2006, a cross-sectional survey was carried out in 206 herds in southern
      Belgium to estimate the proportion of herds with Q fever-seropositive bulk tank
      milk (BTM), i.e. herds with an intra-herd seroprevalence >10%. Of the tested
      herds, 119 (57.8%; 95% CI: 51.1-64.4%) were seropositive. Most had a low antibody
      titre. Of these herds, 50 were randomly subjected to a real time Coxiella
      burnetii PCR analysis. The proportion of herds excreting Coxiella in BTM was
      30.0% with only 2.0% of herds having a high level of shedding. An additional
      questionnaire and logistical regression identified some factors which increased
      the risk of BTM seroconversion (in heifers, drinking water from watercourse or
      well water) and some which decreased it (in heifers, tie- and free-stalling, and
      animals of all age in the same shed; in heifers and cows, shed disinfection).

PMID- 21962830
TI  - Treatment of TNF mediated diseases by selective inhibition of soluble TNF or
      TNFR1.
AB  - The TNF signaling pathway is a valuable target in the therapy of autoimmune
      diseases, and anti-TNF drugs are successfully used to treat diseases such as
      rheumatoid arthritis, Crohn's disease and psoriasis. By their ability to
      interfere with inflammatory processes at multiple levels, these TNF blockers have
      become invaluable tools to inhibit the inflammation induced damage and allow
      recovery of the affected tissues. Unfortunately this therapy has some drawbacks,
      including increased risk of infection and malignancy, and remarkably, the onset
      of new auto-immune diseases. Some of these effects are caused by the unwanted
      abrogation of beneficial TNF signaling. More specific targeting of the
      pathological TNF-induced signaling might lead to broader applicability and
      improved safety. Specificity might be increased by inhibiting the soluble
      TNF/TNFR1 axis while leaving the often beneficial transmembrane TNF/TNFR2
      signaling untouched. This approach looks promising because it inhibits the
      pathological effects of TNF and reduces the side effects, and it opens the way
      for the treatment of other diseases in which TNFR2 inhibition is detrimental. In
      this review we give an overview of in vivo mouse studies of TNF mediated
      pathologies demonstrating that the blockade or genetic deletion of sTNF or TNFR1
      is preferable over total TNF blockade.

PMID- 21962832
TI  - Gender and age differences in mixed metal exposure and urinary excretion.
AB  - BACKGROUND: Little is known about the variation in exposure to toxic metals by
      age and gender and other potential modifying factors. We evaluated age and gender
      differences by measurements of metal/element concentrations in urine in a rural
      population in Matlab, Bangladesh, in three age groups: 8-12 (N=238), 14-15
      (N=107) and 30-88 (N=710) years of age, living in an area with no point sources
      of metal exposure but where elevated water arsenic concentrations are prevalent.
      RESULTS: We found marked differences in urine concentrations of metals and trace
      elements by gender, age, tobacco use, socioeconomic and nutritional status.
      Besides a clearly elevated urinary arsenic concentration in all age groups
      (medians 63-85 MUg As/L), and despite the low degree of contamination from
      industries and traffic, the urine concentrations of toxic metals such as cadmium
      and lead were clearly elevated, especially in children (median 0.31 MUg Cd/L and
      2.9 MUg Pb/L, respectively). In general, women had higher urinary concentrations
      of toxic metals, especially Cd (median 0.81 MUg/L) compared to men (0.66 MUg/L)
      and U (median 10 ng/L in women, compared to 6.4 ng/L in men), while men had
      higher urinary concentrations of the basic and essential elements Ca (69 mg/L in
      men, 30-50 years, compared to 52 mg/L in women), Mg (58 mg/L in men compared to
      50 mg/L in women), Zn (182 MUg/L in men compared to 117 MUg/L in women) and Se
      (9.9 MUg/L in men compared to 8.7 MUg/L in women). Manganese was consistently
      higher in females than in males in all age groups, suggesting a biological
      difference between females and males in Mn metabolism. Increasing socioeconomic
      status decreased the toxic metal exposure significantly in children and
      especially in men. Poor iron status was detected in 17% of children, adolescents
      and women, but only in 6% of men. Also zinc deficiency was more prevalent in
      females than in males. CONCLUSIONS: Women and children seemed to be more at risk
      for toxic metal exposure than men and at the same time more vulnerable to
      micronutrient deficiency. Higher concentrations of the toxic metals in urine in
      women are likely to reflect an increased gastrointestinal absorption of these
      metals at micronutrient deficiency, such as low body iron stores and Zn
      deficiency. Higher urinary concentrations of the essential elements in men likely
      reflect a better nutritional status. There is a need for information on exposure,
      lifestyle and socioeconomic factors, stratified by gender and age, for the
      purpose of conducting balanced risk assessment and management that considers such
      differences.

PMID- 21962833
TI  - Quadriplex real-time PCR (qPCR) assay for human-canine-feline species
      identification and nuclear DNA quantification.

PMID- 21962834
TI  - Distribution of extended-spectrum beta-lactamase genes using a commercial DNA
      micro-array system.
AB  - Extended-spectrum beta-lactamase (ESBL) genes are distributed worldwide and their
      epidemiology is complex. Using the Check-ESBL assay, the distribution of class A
      ESBL genes in clinical isolates of aerobic Gram-negative bacilli from three
      laboratories in the East of The Netherlands was determined. Four patient
      categories were distinguished: (i) patients admitted to an intensive care unit
      (ICU); (ii) non-ICU inpatients; (iii) outpatients admitted less than a year
      before collection of the isolate, (<1); (iv) outpatients admitted more than one
      year prior to isolate collection or who had never been hospitalized (>1). From
      February 2009 until March 2010, out of 491 putative ESBL-positive isolates
      detected by the Vitek2 or Phoenix automated sensitivity testing systems, ESBL
      genes were detected in 247 (50.3%) by the Check-ESBL assay. Of these, 116 were
      from hospitalized patients (35 ICU, 81 non-ICU) and 131 were from outpatients (43
      <1, 88 >1). In all, 274 ESBL genes were identified in these 247 isolates: 153 CTX
      M-1 group (predominantly in E. coli and K. pneumoniae, 70.4% and 51.6%
      respectively), 67 CTX-M-9 group (predominantly in E. cloacae, 57.9%), 32 SHV, 14
      TEM and 8 CTX-M-2 group. ESBL-producing E. cloacae were significantly more common
      in hospitalized patients than in outpatients, 20.7% and 3.8% respectively
      (P=0.001). CTX-M-9 group ESBLs were significantly more prevalent in ICU patients
      (P=0.003), whereas SHV ESBLs were more common in hospitalized patients than in
      outpatients (P<0.001). There was no significant difference in distribution of
      ESBL genes between the two outpatient groups.

PMID- 21962835
TI  - Transition to intensive care nursing: a state-wide, workplace centred program-12
      years on.
AB  - In November 1999, the Queensland Health (QH) Transition to Practice Nurse
      Education Program - Intensive Care (TPNEP-IC) was initiated in QH Intensive Care
      Units (ICUs) across Queensland. This 12-month, state-wide, workplace based
      education program has set minimum standards for intensive care nursing education
      and therefore minimum standards for intensive care nursing practice in QH. In the
      12 years of operation, 824 nurses have completed TPNEP-IC, 761 achieving academic
      credit status and 453 utilising this academic credit status to undertake
      postgraduate study in critical/intensive care nursing at three Queensland
      universities. These outcomes were achieved through the appointment of nurse
      educators within ICUs who, through a united and strong commitment to this state
      wide approach formed collaborative professional networks, which resulted in the
      development, implementation and maintenance of the program. Furthermore, these
      networks enabled a framework of support for discussion and dissemination of
      evidence based practice, to endorse quality processes for TPNEP-IC and to nurture
      leadership potential among educators. Challenges to overcome included obtaining
      adequate resources to support all aspects of the program, gaining local
      management and administrative support, and embedding TPNEP-IC within ICU culture.
      The 12 years of operation of the program have demonstrated its long term
      sustainability. The program is being launched through a new blended learning
      approach utilising e-learning strategies. To capitalise on the current success, a
      strong commitment by all stakeholders will be required to ensure the ongoing
      sustainability of the program.

PMID- 21962836
TI  - Spermatozoa in the sperm-peak-fraction of the boar ejaculate show a lower flow of
      Ca(2+) under capacitation conditions post-thaw which might account for their
      higher membrane stability after cryopreservation.
AB  - Boar spermatozoa collected in the ejaculate sperm peak-portion (P1, first 10 mL
      of the sperm-rich fraction, SRF), had shown a higher resilience to freezing and
      thawing compared to spermatozoa from the rest of the ejaculate (2nd portion of
      the SRF plus the post-sperm-rich fraction, PSRF), even when using a simplified
      freezing technique, as long as spermatozoa were incubated in their own seminal
      plasma (SP). This experiment studied the stability of P1- and SRF-P1 boar
      spermatozoa frozen in MiniFlatPacks (MFP), post-thaw, using flow cytometry. Since
      spermatozoa from either portion showed similar cryosurvival and low proportions
      of unstable membranes (<3%, annexin-V/propidium iodide staining), and only a
      tendency for SRF-P1 live spermatozoa to depict acrosome exocytosis (FITC
      PNA/PI/H33342); they were explored for Ca(2+) contents using a Fluo-4 probe under
      in vitro capacitating conditions (mBO+ medium), as well they were tested for
      their ability to sustain a short Ca(2+)-ionophore (A23187) in vitro challenge.
      The proportions of live spermatozoa depicting high Ca(2+)-levels were initially
      <2% but increased over incubation time, particularly in SRF-P1(P<0.05), while
      proportions of live spermatozoa with low Ca(2+)-levels were basically constant
      over incubation time (~11-14%), for either portion. Incubation in capacitation
      medium did not modify the proportions of low-Ca(2+) but dramatically increased
      the proportions of high-Ca(2+) spermatozoa (P<0.001) already after 15 min
      exposure, highest for SRF-P1 spermatozoa. While the proportion of live
      spermatozoa with intact acrosome was significantly decreased among SRF-P1
      (P<0.001), that of P1-spermatozoa remained unchanged, probably owing to the
      lowest relative content of cytosolic Ca(2+). The results suggest that spermatozoa
      in the P1-portion are more resilient to express acrosome exocytosis post-thaw
      compared to those bathing in the rest of the SRF-fraction when cryopreserved
      using a simplified technique, in MFPs.

PMID- 21962837
TI  - Expression of KIT in the ovary, and the role of somatic precursor cells.
AB  - KIT is a type III receptor protein tyrosine kinase, and KITL its cognate ligand.
      KIT can mediate its effects via several intracellular signalling pathways, or by
      formation of a cell-cell anchor with its ligand. Through these mechanisms, KIT
      controls fundamental cellular processes, including migration, proliferation,
      differentiation and survival. These cellular processes are modulated by soluble
      KIT, a cleavage product of KIT, generated at the cell membrane. A cell-retained
      KIT cleavage fragment also arises from this cleavage event. This cleavage
      fragment must be distinguished from truncated KIT (trKIT), which originates
      through cryptic promoter usage. The expression of trKIT is highly restricted to
      postmeiotic germ cells in the testis. In contrast, KIT, together with its
      cleavage products, is present in somatic cells and germ cells in the gonads of
      both sexes. A functional KITL/KIT system is mandatory for normal population of
      the gonads by germ cells. Signalling via the KITL/KIT system promotes the growth,
      maturation, and survival of germ cells within the gonads, and prevents meiotic
      entry and progression. In addition to its importance in germ cell biology, the
      KITL/KIT system is crucial for gonadal stromal differentiation. During foetal
      life, KIT is expressed by testicular stromal precursor cells, which develop into
      Leydig cells. In the ovary, stromal cell KIT expression accompanies theca layer
      development around advanced follicles. After ovulation, KIT-immunopositive cells
      translocate from the theca layer to the luteal ganulosa where they contribute to
      a delicate cellular network that extends between the fully luteinised large
      luteal cells. In the outer regions of the developing corpus luteum, a highly
      conspicuous subpopulation of KIT/CD14-double-immunopositive cells can be
      observed. KIT/CD14-double-immunopositive cells are also seen in the
      haematopoietic-like colonies of long-term granulosa cultures established from
      late antral follicles. These cultures demonstrate expression of pluripotency
      marker genes such as octamer binding transcription factor-3/4 and sex determining
      region Y-box 2. The KIT/CD14-double-immunopositive cells can be purified and
      enriched by KIT-immunopositive magnetic cell sorting. Subsequent exposure of the
      KIT-expressing cells to the hanging drop culture method, combined with
      haematopoietic differentiation medium, provides the signals necessary for their
      differentiation into endothelial and steroidogenic cells. This suggests that
      monocyte-derived multipotent cells are involved in ovarian tissue remodelling. In
      summary, multicelluar KITL/KIT signalling organizes the stroma in the ovary and
      testis; monocyte-derived multipotent cells may be involved.

PMID- 21962839
TI  - Infection control: accomplishments and priorities from an individual, state,
      national, and international perspective.

PMID- 21962840
TI  - Methicillin-resistant Staphylococcus aureus from dental school clinic surfaces
      and students.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) isolated from
      frequently touched dental school clinic surfaces were compared with MRSA isolated
      nasal cultures of dental students. METHOD: Sixty-one dental students and 95
      environmental surfaces from 7 clinics were sampled using SANICULT (Starplex
      Scientific Inc, Etobicoke, Ontario, Canada) swabs. Antimicrobial susceptibility
      testing was performed, and pulsed-field gel electrophoresis analysis, the mecA
      gene, multilocus sequence type, and SCCmec type were determined by polymerase
      chain reaction and sequencing. RESULTS: Thirteen (21%) dental students and 8
      (8.4%) surfaces were MRSA positive. Three MRSA strains were SCCmec type IV,
      whereas 3 were nontypeable isolates and Panton-Valentine leukocidin positive
      (PVL+), and none were USA300. One surface and 1 student isolate shared the same
      multilocus sequence type ST 8 and were 75% related. Two groups of students
      carried the same MRSA strains. CONCLUSION: The MRSA-positive samples were from 4
      of 7 dental clinics. In addition, 21% of the dental students carried MRSA, which
      is > 10 times higher than the general public and twice as frequent as in other
      university students. This is the first study to characterize MRSA from dental
      clinic surfaces and dental students and suggests that both may be reservoirs for
      MRSA. Further studies are needed to verify this premise.

PMID- 21962841
TI  - Hepatic blood flow distribution and performance in conventional and novel Y-graft
      Fontan geometries: a case series computational fluid dynamics study.
AB  - OBJECTIVES: A novel Y-shaped baffle has been proposed for the Fontan operation
      with promising initial results. However, previous studies have relied either on
      idealized models or a single patient-specific model. The objective of this study
      is to comprehensively compare the hemodynamic performance and hepatic blood flow
      distribution of the Y-graft Fontan baffle with 2 current designs using multiple
      patient-specific models. METHODS: Y-shaped and tube-shaped grafts were virtually
      implanted into 5 patient-specific Glenn models forming 3 types of Fontan
      geometries: Y-graft, T-junction, and offset. Unsteady flow simulations were
      performed at rest and at varying exercise conditions. The hepatic flow
      distribution between the right and left lungs was carefully quantified using a
      particle tracking method. Other physiologically relevant parameters such as
      energy dissipation, superior vena cava pressure, and wall shear stress were
      evaluated. RESULTS: The Fontan geometry significantly influences the hepatic flow
      distribution. The Y-graft design improves the hepatic flow distribution
      effectively in 4 of 5 patients, whereas the T-junction and offset designs may
      skew as much as 97% of hepatic flow to 1 lung in 2 cases. Sensitivity studies
      show that changes in pulmonary flow split can affect the hepatic flow
      distribution dramatically but that some Y-graft and T-junction designs are
      relatively less sensitive than offset designs. The Y-graft design offers moderate
      improvements over the traditional designs in power loss and superior vena cava
      pressure in all patients. CONCLUSIONS: The Y-graft Fontan design achieves overall
      superior hemodynamic performance compared with traditional designs. However, the
      results emphasize that no one-size-fits-all solution is available that will
      universally benefit all patients and that designs should be customized for
      individual patients before clinical application.

PMID- 21962842
TI  - Long-term evaluation of biological versus mechanical prosthesis use at
      reoperative aortic valve replacement.
AB  - OBJECTIVES: Recent evidence indicated that the use of a bioprosthesis in young
      patients at first-time aortic valve replacement (AVR) is associated with an
      increased reoperation risk, but not with an increase in long-term mortality, when
      compared with the use of a mechanical valve. However, at reoperative AVR, follow
      up data by prosthesis type have been lacking from the literature. Therefore, we
      examined long-term survival and valve-related complications according to the type
      of prosthesis used at reoperative AVR. METHODS: We studied 437 patients who
      underwent reoperative AVR, at a mean age of 58.6 +/- 14.2 years, for failure of a
      previously implanted aortic valve prosthesis. Thirty-day mortality at reoperative
      AVR was 6% (n = 27). A bioprosthesis was used in 135 (31%) patients. Patients
      were subsequently followed up for a mean of 7.6 +/- 6.8 years after reoperative
      AVR. RESULTS: The use of a bioprosthesis at reoperative AVR was not associated
      with impaired survival on adjusted analysis (hazard ratio [HR], 0.8 +/- 0.4; P =
      .6). Freedom from thromboembolism, and endocarditis were similar between valve
      types (both P > .05); however, late postoperative major hemorrhage occurred only
      in patients who received a mechanical prosthesis at reoperative AVR. Risk factors
      for third-time AVR included the use of a bioprosthesis (HR, 14.0) and younger age
      (HR, 1.05 per decreasing year) at reoperative AVR (both P < .001). Thirty-day
      mortality of third-time AVR was 4% (n = 1/27). CONCLUSIONS: At reoperative AVR,
      the use of a bioprosthesis is associated with equivalent long-term survival
      compared with a mechanical prosthesis. Patients who receive a bioprosthesis at
      reoperative AVR are less likely to experience major hemorrhage but more likely to
      require third-time AVR, albeit with an acceptable third-time perioperative
      mortality risk. Therefore, the patient's informed preferences regarding
      prosthesis choice should prevail, even in a reoperative context.

PMID- 21962843
TI  - Circulating interferon-gamma-inducible Cys-X-Cys chemokine receptor 3 ligands are
      elevated in humans with aortic aneurysms and Cys-X-Cys chemokine receptor 3 is
      necessary for aneurysm formation in mice.
AB  - OBJECTIVE: Inflammation is associated with the formation of aortic aneurysm. This
      study investigates the role of inducible Cys-X-Cys chemokine receptor 3 and its
      ligands in the pathogenesis of arterial aneurysms. METHODS: Plasma samples from
      patients with or without a diagnosis of thoracic aortic aneurysms were analyzed
      by enzyme-linked immunosorbent assay for the T-helper 1 cytokine interferon-gamma
      and the interferon-gamma-inducible chemokine receptor 3 ligands: interferon
      inducible protein-10, interferon-inducible T-cell alpha chemoattractant, and
      monokine induced by interferon gamma. Patient charts were reviewed for
      demographics, initial aortic diameter, and growth rates. Aneurysm diameter and
      growth rates were correlated with plasma cytokine and chemokine levels using
      linear regression analysis. We used an animal model of aneurysm formation, where
      calcium chloride is applied topically to the carotid arteries of wild-type and
      Cys-X-Cys chemokine receptor 3(-/-) mice. After 10 weeks, the arteries were
      harvested and analyzed by histology and immunohistochemistry. RESULTS: Patients
      with thoracic aortic aneurysms had significant elevations in circulating
      interferon-gamma, interferon-inducible protein-10, interferon-inducible T-cell
      alpha chemoattractant, and monokine induced by interferon gamma compared with
      referent patients (P < .001). Cytokine and chemokine plasma levels did not
      correlate with aneurysm size or growth rates. Cys-X-Cys chemokine receptor 3(-/-)
      mice were protected from aneurysm formation and showed decreased vascular
      infiltration by CD45(+) leukocytes. CONCLUSIONS: Elevated plasma levels of
      interferon-gamma and Cys-X-Cys chemokine receptor 3-binding chemokines are
      present in patients with thoracic aortic aneurysms. The Cys-X-Cys chemokine
      receptor 3 receptor is necessary for vascular inflammation and the formation of
      arterial aneurysms in mice.

PMID- 21962844
TI  - Mechanical energy estimation during walking: validity and sensitivity in typical
      gait and in children with cerebral palsy.
AB  - Gait efficiency in children with cerebral palsy is usually quantified by
      metabolic energy expenditure. Mechanical energy estimations, however, can be a
      valuable supplement as they can be assessed during gait analysis and plotted over
      the gait cycle, thus revealing information on timing and sources of increases in
      energy expenditure. Unfortunately, little information on validity and sensitivity
      exists. Three mechanical estimation approaches: (1) centre of mass (CoM)
      approach, (2) sum of segmental energies (SSE) approach and (3) integrated joint
      power approach, were validated against oxygen consumption and each other.
      Sensitivity was assessed in typical gait and in children with diplegia. CoM
      approach underestimated total energy expenditure and showed poor sensitivity. SSE
      approach overestimated energy expenditure and showed acceptable sensitivity.
      Validity and sensitivity were best in the integrated joint power approach. This
      method is therefore preferred for mechanical energy estimation in children with
      diplegia. However, mechanical energy should supplement, not replace metabolic
      energy, as total energy expended is not captured in any mechanical approach.

PMID- 21962845
TI  - Do lower-extremity joint dynamics change when stair negotiation is initiated with
      a self-selected comfortable gait speed?
AB  - Previous research on the biomechanics of stair negotiation has ignored the effect
      of the approaching speed. We examined if initiating stair ascent with a
      comfortable self-selected speed can affect the lower-extremity joint moments and
      powers as compared to initiating stair ascent directly in front of the stairs.
      Healthy young adults ascended a custom-built staircase instrumented with force
      platforms. Kinematics and kinetics data were collected simultaneously for two
      conditions: starting from farther away and starting in front of the stairs and
      analyzed at the first and second ipsilateral steps. Results showed that for the
      first step, participants produced greater peak knee extensor moment, peak hip
      extensor and flexor moments and peak hip positive power while starting from
      farther away. Also, for both the conditions combined, participants generated
      lesser peak ankle plantiflexor, greater peak knee flexor moment, lesser peak
      ankle negative power and greater peak hip negative power while encountering the
      first step. These results identify the importance of the starting position in
      experiments dealing with biomechanics of stair negotiation. Further, these
      findings have important implications for studying stair ascent characteristics of
      other populations such as older adults.

PMID- 21962846
TI  - The effects of grade and speed on leg muscle activations during walking.
AB  - Compared to level walking, additional muscle actions are required to raise and
      lower the center of mass during uphill and downhill walking, respectively.
      However, it remains unclear which muscle recruitment strategies are employed at
      typical grades when walking over a range of speeds. Based on previous reports, we
      hypothesized that, across a range of walking speeds, hip, knee, and ankle
      extensor muscle activations would increase with steeper uphill grade, but only
      knee extensor muscle activations would increase with steeper downhill grade. We
      also hypothesized that these changes in muscle activations with grade would
      become more pronounced at faster walking speeds. To test these hypotheses, 10
      young adults (5M/5F) walked on a standard treadmill at seven grades (0 degrees ,
      +/- 3 degrees , +/- 6 degrees , and +/- 9 degrees ) and three speeds (0.75, 1.25,
      and 1.75 ms(-1)). We quantified the stance phase electromyographic activities of
      the gluteus maximus (GMAX), biceps femoris (BF), rectus femoris (RF), vastus
      medialis (VM), medial gastrocnemius (MG), and soleus (SOL) muscles. On average,
      compared to level walking, hip (BF: 635%, GMAX: 345%), knee (RF: 165%, VM: 366%),
      and ankle (MG: 175%, SOL: 136%) extensor muscle activities increased to walk up 9
      degrees , but only knee (RF: 310%, VM: 246%) extensor muscle activities increased
      to walk down 9 degrees . Further, these changes in muscle activations with grade
      became greater with faster walking speed. We conclude that people employ distinct
      uphill (hip, knee, and ankle extensors) and downhill (knee extensors) muscle
      recruitment strategies generally across walking speeds and progressively with
      steeper grade.

PMID- 21962847
TI  - Joint coordination in young and older adults during quiet stance: effect of
      visual feedback of the center of pressure.
AB  - How aging affects body sway and joint coordination during quiet standing was
      investigated under two visual feedback conditions provided on a monitor screen:
      fixed and moving cursor representing the center of pressure (COP) position
      measured by a platform. The across-time joint motion variance of ankle, knee,
      hip, mid-trunk, and cervical spine leading to COP displacement was analyzed using
      the uncontrolled manifold approach. The body sway was assessed by the COP
      displacement. Young and older adults showed greater ankle joint contribution to
      COP displacement than the other joints. However, older adults showed larger
      variability of knee and mid-trunk joint motions than young adults. During the
      moving condition, the ankle joint contribution decreased and hip joint
      contribution increased for both groups, but the COP displacement increased only
      for the older adults. We conclude that joint coordination and body sway during
      quiet standing can be modified by providing COP visual feedback and that joint
      coordination is affected by aging.

PMID- 21962848
TI  - A photosynthetic rotating annular bioreactor (Taylor-Couette type flow) for
      phototrophic biofilm cultures.
AB  - In their natural environment, the structure and functioning of microbial
      communities from river phototrophic biofilms are driven by biotic and abiotic
      factors. An understanding of the mechanisms that mediate the community structure,
      its dynamics and the biological succession processes during phototrophic biofilm
      development can be gained using laboratory-scale systems operating with
      controlled parameters. For this purpose, we present the design and description of
      a new prototype of a rotating annular bioreactor (RAB) (Taylor-Couette type flow,
      liquid working volume of 5.04 L) specifically adapted for the cultivation and
      investigation of phototrophic biofilms. The innovation lies in the presence of a
      modular source of light inside of the system, with the biofilm colonization and
      development taking place on the stationary outer cylinder (onto 32 removable
      polyethylene plates). The biofilm cultures were investigated under controlled
      turbulent flowing conditions and nutrients were provided using a synthetic medium
      (tap water supplemented with nitrate, phosphate and silica) to favour the biofilm
      growth. The hydrodynamic features of the water flow were characterized using a
      tracer method, showing behaviour corresponding to a completely mixed reactor.
      Shear stress forces on the surface of plates were also quantified by computer
      simulations and correlated with the rotational speed of the inner cylinder. Two
      phototrophic biofilm development experiments were performed for periods of 6.7
      and 7 weeks with different inoculation procedures and illumination intensities.
      For both experiments, biofilm biomasses exhibited linear growth kinetics and
      produced 4.2 and 2.4 mg cm(-)2 of ash-free dry matter. Algal and bacterial
      community structures were assessed by microscopy and T-RFLP, respectively, and
      the two experiments were different but revealed similar temporal dynamics. Our
      study confirmed the performance and multipurpose nature of such an innovative
      photosynthetic bioreactor for phototrophic biofilm investigations.

PMID- 21962849
TI  - Sonolytic degradation of dimethoate: kinetics, mechanisms and toxic intermediates
      controlling.
AB  - The sonolytic degradation of aqueous solutions of dimethoate, O,O-dimethyl S-[2
      (methylamino)-2-oxoethyl]dithiophosphate, was examined. Optimal degradation rates
      were obtained at 619 kHz for continuous sonolysis and 406 kHz for pulse
      sonolysis. The primary pathways for degradation include hydroxyl radical
      oxidation, hydrolysis and pyrolysis on collapsing cavitation bubble interfaces.
      Reaction mechanisms coupled with the corresponding kinetic models are proposed to
      reproduce the observed concentration versus time profiles for dimethoate,
      omethoate and N-(methyl) mercaptoacetamide during sonolysis. The oxidation and
      hydrolysis of dimethoate and omethoate occurred at the water-bubble interface was
      the rate-determining step for sonolytic overall degradation of dimethoate. More
      than 90% toxicity of dimethoate was reduced within 45 min ultrasonic irradiation.
      Ferrous ion at micro molar level can significantly enhance the sonolytic
      degradation of dimethoate and effectively reduce the yields of toxic intermediate
      omethoate.

PMID- 21962850
TI  - Offspring of parents with recurrent depression: which features of parent
      depression index risk for offspring psychopathology?
AB  - BACKGROUND: Parental depression is associated with an increased risk of
      psychiatric disorder in offspring, although outcomes vary. At present relatively
      little is known about how differences in episode timing, severity, and course of
      recurrent depression relate to risk in children. The aim of this study was to
      consider the offspring of parents with recurrent depression and examine whether a
      recent episode of parental depression indexes risk for offspring psychopathology
      over and above these other parental depression features. METHODS: Three hundred
      and thirty seven recurrently depressed parents and their offspring (aged 9-17)
      were interviewed as part of an ongoing study, the 'Early Prediction of Adolescent
      Depression Study'. The Child and Adolescent Psychiatric Assessment was used to
      assess two child outcomes; presence of a DSM-IV psychiatric disorder and number
      of DSM-IV child-rated depression symptoms. RESULTS: Children whose parents had
      experienced a recent episode of depression reported significantly more depression
      symptoms, and odds of child psychiatric disorder were doubled relative to
      children whose parents had not experienced a recent episode of depression. Past
      severity of parental depression was also significantly associated with child
      depression symptoms. LIMITATIONS: Statistical analyses preclude causal
      conclusions pertaining to parental depression influences on offspring
      psychopathology; several features of parental depression were recalled
      retrospectively. CONCLUSIONS: This study suggests that particular features of
      parental depression, specifically past depression severity and presence of a
      recent episode, may be important indicators of risk for child psychiatric
      disorder and depressive symptoms.

PMID- 21962851
TI  - Facile synthesis of Ag/GNS-g-PAA nanohybrids for antimicrobial applications.
AB  - A facile and efficient aqueous phase-based strategy to synthesize silver
      nanocrystal/graphene nanosheet (GNS) nanohybrids at room temperature, via in situ
      poly(acrylic acid) (PAA) grafting followed by attachment of Ag nanocrystals, was
      reported. In the presence of PAA-grafted GNSs, Ag nanoparticles were in situ
      generated from AgNO(3) aqueous solution without any additional reducing agent or
      complicated treatment. They readily attached to the GNS surfaces, leading to
      Ag/GNS-g-PAA nanohybrids. The products of the Ag/GNS-g-PAA nanohybrids were
      examined by transmission electron microscope, thermogravimetric analyzer, X-ray
      powder diffraction analyzer, and energy disperse spectroscopy. The Ag
      nanoparticles can be uniformly deposited on the surfaces of functionalized GNSs
      with a controlled size distribution of 4-8 nm. Furthermore, the Ag/GNS-g-PAA
      nanohybrids exhibit good antimicrobial activity against Gram-positive
      Staphylococcus aureus and Gram-negative Escherichia coli. The mean diameters of
      the zones of inhibition are 11.4 mm and 9.9 mm, respectively, for S. aureus and
      E. coli. The simplicity, efficiency and large-scale availability of nanohybrids
      combined with good antimicrobial activity make them attractive for graphene-based
      biomaterials.

PMID- 21962852
TI  - Synthesis, dispersion, and cytocompatibility of graphene oxide and reduced
      graphene oxide.
AB  - The synthesis, characterization, and toxicity of graphene oxide and reduced
      graphene oxide are reported. Prior to the cytocompatibility tests the stability
      of the suspensions in a wide range of concentrations (3.125-100 MUg/mL) of three
      different dispersants is studied. Polyethylene glycol (PEG), polyethylene glycol
      polypropylene glycol-polyethylene glycol (Pluronic P123), and sodium deoxycholate
      (DOC) are investigated as the dispersants. The toxicity depends on the type of
      dispersant and concentration of the nanomaterials in the suspensions. Detailed
      analysis suggests that graphene oxide functionalized with PEG in the
      concentration range between 3125 MUg/mL and 25 MUg/mL exhibits the best
      biocompatibility with mice fibroblast cells (line L929).

PMID- 21962853
TI  - Formation of eLiposomes as a drug delivery vehicle.
AB  - This paper discusses the formation of eLiposomes, defined as a liposome with
      internal emulsion droplets. Liposomes have been investigated as passively
      targeted drug carriers due to their ability to deliver drugs to a cancerous tumor
      via the enhanced permeability and retention (EPR) effect. The enclosed emulsion
      droplets in an eLiposome add the ability to further control the location and time
      of release from the liposome with ultrasound. Emulsion droplets were formed from
      perfluorohexane (PFC6) by sonication at 20 kHz and stabilized with dipalmitoyl
      phosphatidyl choline (DPPC). The size of the resulting droplets was reduced to
      approximately 100 nm or 50 nm by extrusion through polycarbonate filters of the
      same size at 50 degrees C. Small unilamellar vesicles (SUVs) were prepared from
      DPPC by thin film hydration and extrusion through a 50 nm filter. Interdigitated
      DPPC sheets were prepared from the SUVs by the addition of ethanol to a
      concentration of 3M. Excess ethanol was removed by centrifugation washing. The
      sheets were mixed with emulsion and the solution was heated to 50 degrees C,
      resulting in the refolding of the DPPC sheets into closed vesicles. Emulsion
      droplets were encapsulated inside of the newly formed eLiposomes. The size of the
      eLiposomes was reduced by extrusion. Cryogenic transmission electron microscopy
      (cryoTEM) and negative-staining TEM were used to image the emulsion droplets and
      the eLiposomes. Encapsulation of emulsion droplets was verified by rotating the
      microscope stage of cryoTEM samples.

PMID- 21962854
TI  - Generation of amphoteric surfaces via glow-discharge technique with single
      precursor and the behavior of bovine serum albumin at the surface.
AB  - Amphoteric surfaces were generated on silicone substrates via plasma
      polymerization technique using a single monomer; diethyl allyl phosphate (DAP).
      Surface characterization was performed by the means of contact angle titration
      and Fourier transform infrared (FTIR) spectroscopy. The surface of silicone was
      found to be slightly basic with an apparent basicity of 0.12 MUmol/m(2) while
      plasma surface modification made the surfaces amphoteric with the surface
      acid/base concentration adjustable by varying plasma parameters. The adsorption
      of model protein; bovine serum albumin (BSA) on the surfaces was found to be
      correlated to the surface acid/base ratio. Percent reduction on modified surfaces
      compared to bare silicone surface was 32, 59 and 92% for 20 W 5 min, 60 W 5 min
      and 100 W 5 min modified surfaces respectively. Conformational change of BSA upon
      adsorption to the surfaces was investigated with FTIR-ATR spectroscopy. It has
      been shown that BSA preserves more of its secondary structure upon adsorption to
      plasma modified surfaces than the bare silicone surface. It has been concluded
      that DAP modified surfaces reduces the amount of protein adsorption on the
      surfaces due to the modified surfaces amphoteric nature and the ability of
      modified surfaces to preserve the secondary structure of adsorbed protein better
      than the bare silicone surface.

PMID- 21962855
TI  - [Questions about the ADVANCE study].
AB  - The symptoms of secondary hyperparathyroidism (SHPT) were substantially changed
      by the availability of cinacalcet (CC). The recent ADVANCE study, which was a
      prospective randomized trial comparing two treatment strategies-CC plus low doses
      of calcitriol analogues (CA) versus higher doses of CA without CC-reports the
      absence of difference in the primary endpoint, i.e. coronary artery calcification
      score progression after 12 months. The progression of coronary calcification was
      related to the initial hypercalcemia and hyperphosphataemia, and low serum PTH
      level. What was the rationale for defining SHPT with only serum PTH value of more
      than 300 pg/mL or more than 150 pg/mL associated with a high Ca*P product? Why
      was this coronary score chosen as the primary endpoint and why was a seemingly
      short observational period used? Is it correct to consider all forms of SHPT
      equivalent in terms of set point, response to conventional treatment, or vascular
      and bone consequences? Why are the biological values of patients not provided?
      Were the CAs, dialysate calcium, and PTH assay values really equal? Why were only
      calcium-based phosphate binders used? The main controversial point of the study
      was to consider all HPT cases as equivalent and able to be treated by one fixed
      strategy. Therefore, the nephrologist community should conduct relevant
      independent studies in order to improve the diagnosis and treatment of SHPT.

PMID- 21962856
TI  - [Society of Pediatric Nephrology Marrakech 25 to 27 November 2010].

PMID- 21962857
TI  - Herpesvirus active replication in multiple sclerosis: a genetic control?
AB  - Although the etiology of multiple sclerosis (MS) is unknown, it is generally
      believed that genetic, immunologic, and environmental factors are involved. The
      objectives of this study were: 1. to analyze if a genetic control could explain
      why HHV-6 would be able to actively replicate in a subset of MS patients but not
      in controls; 2. to study if MS patients with HHV-6 active replication are
      clinically different from those without HHV-6 active replication. A total of 195
      MS patients and 195 controls were analyzed for two SNPs at the MHC2TA locus and
      two SNPs at the CD46 locus. Furthermore, the MS cohort was analyzed by PCR for
      the detection of HHV-6 genomes in five serum samples collected every six months
      along two-year follow-up. We found that 59/195 (30.2%) MS patients had at least
      one HHV-6 positive serum sample. No statistical significant difference was found
      for the two genes when the comparison was made between MS patients and controls;
      however, a statistical significance was found for the two polymorphisms of MHC2TA
      when we compared MS patients with active replication and controls (p=0.0000004
      for rs4774C and p=0.011 for rs3087456G). Furthermore, increased significant
      differences were found for MHC2TA and CD46 when we compared interferon beta
      responders and non-responders within MS patients. In conclusion, we describe a
      gene-environment interaction in MS patients between HHV-6 and MHC2TA and CD46
      that should be further studied to clarify if that interaction could be a genetic
      control. The results show that MS patients without HHV-6 active replication are
      better responders to interferon beta treatment than those with HHV-6 active
      replication.

PMID- 21962858
TI  - Need for culture specific tools to assess social cognition in schizophrenia.

PMID- 21962859
TI  - Convective heat transfer around vertical jet fires: an experimental study.
AB  - The convection heat transfer phenomenon in vertical jet fires was experimentally
      analyzed. In these experiments, turbulent propane flames were generated in
      subsonic as well as sonic regimes. The experimental data demonstrated that the
      rate of convection heat transfer increases by increasing the length of the flame.
      Assuming the solid flame model, the convection heat transfer coefficient was
      calculated. Two equations in terms of adimensional numbers were developed. It was
      found out that the Nusselt number attains greater values for higher values of the
      Rayleigh and Reynolds numbers. On the other hand, the Froude number was analyzed
      only for the subsonic flames where the Nusselt number grows by this number and
      the diameter of the orifice.

PMID- 21962860
TI  - Adsorption and desorption performance of benzene over hierarchically structured
      carbon-silica aerogel composites.
AB  - Hierarchically structured carbon-silica aerogel (CSA) composites were synthesized
      from cheap water glass precursors and granulated activated carbon via a post
      synthesis surface modification with trimethylchlorosilane (TMCS) and a low-cost
      ambient pressure drying procedure. The resultant CSA composites possess
      micro/mesoporous structure and hydrophobic surface. The adsorption and desorption
      performance of benzene on carbon-silica aerogel composite (CSA-2) under static
      and dynamic conditions were investigated, comparing with pure silica aerogel (CSA
      0) and microporous activated carbon (AC). It was found that CSA-2 has high
      affinity towards aromatic molecules and fast adsorption kinetics. Excellent
      performance of dynamic adsorption and desorption observed on CSA-2 is related to
      its higher adsorption capacity than CSA-0 and less mass transfer resistance than
      AC, arising from the well-developed microporosity and open foam mesostructure in
      the CSA composites.

PMID- 21962861
TI  - Effects of gene-augmentation on the formation, characteristics and microbial
      community of 2,4-dichlorophenoxyacetic acid degrading aerobic microbial granules.
AB  - Development of 2,4-dichlorophenoxyacetic acid (2,4-D) degrading aerobic granular
      sludge was conducted in two sequencing batch reactors (SBR) with one bioaugmented
      with a plasmid pJP4 donor strain Pseudomonas putida SM1443 and the other as a
      control. Half-matured aerobic granules pre-grown on glucose were used as the
      starting seeds and a two-stage operation strategy was applied. Granules capable
      of utilizing 2,4-D (about 500 mg/L) as the sole carbon source was successfully
      cultivated in both reactors. Gene-augmentation resulted in the enhancement of 2,4
      D degradation rates by the percentage of 65-135% for the granules on Day 18, and
      6-24% for the granules on Day 105. Transconjugants receiving plasmid pJP4 were
      established in the granule microbial community after bioaugmentation and
      persisted till the end of operation. Compared with the control granules, the
      granules in the bioaugmented reactor demonstrated a better settling ability,
      larger size, more abundant microbial diversity and stronger tolerance to 2,4-D.
      The finally obtained granules in the bioaugmented and control reactor had a
      granule size of around 600 MUm and 500 MUm, a Shannon-Weaver diversity index (H)
      of 0.96 and 0.55, respectively. A shift in microbial community was found during
      the granulation process.

PMID- 21962862
TI  - Emulsion stabilization using ionic liquid [BMIM]+[NTf2]- and performance
      evaluation on the extraction of chromium.
AB  - This study focuses on the role of a hydrophobic ionic liquid 1-butyl-3
      methylimidazolium bis(trifluoromethylsulfonyl)imide, [BMIM](+)[NTf(2)](-) in the
      preparation of emulsion liquid membrane (ELM) phase containing kerosene as
      solvent, Span 80 as surfactant, NaOH as internal phase and TOMAC (tri-n
      octylmethylammonium chloride) a second ionic liquid as carrier. The first time
      used [BMIM](+)[NTf(2)](-) in ELM was found to play the role of a stabilizer. The
      emulsion prepared using [BMIM](+) [NTf(2)](-) has a long period of stability of
      about 7h (at 3% (w/w) of [BMIM](+)[NTf(2)](-)) which otherwise has a brief
      stability up to only 7 min. The stability of the emulsion increases with the
      increase in concentration of [BMIM](+)[NTf(2)](-) up to 3% (w/w). Nevertheless,
      with further increase in concentration of [BMIM](+)[NTf(2)](-), a reduction in
      the stability occurs. The extraction experiments were carried out after holding
      the ELM for 2h after the preparation and a removal efficiency of approximately
      80% was obtained for Cr. The destabilization of the emulsion was studied by
      observing the change in the interface height. An empirical correlation for the
      stability of the emulsion has been proposed.

PMID- 21962863
TI  - Adsorption behavior of some aromatic compounds on hydrophobic magnetite for
      magnetic separation.
AB  - In this study, a hydrophobic magnetite coated with an alkyl chain or a phenyl
      group on the surface was prepared and used as an adsorbent to investigate the
      adsorption behavior of aromatic compounds having various values of log P(ow)
      (phenol 1.46, benzonitrile 1.56, nitrobenzene 1.86, benzene 2.13, toluene 2.73,
      chlorobenzene 2.84 and o-dichlorobenzene 3.38) onto hydrophobic magnetite. The
      hydrophobic magnetites were modified with stearic acid and
      phenyltrimethoxysilane, and the modification amounts were 9.84 * 10(-3) and 4.17
      * 10(-2)mmol/g, respectively. The aromatic compounds used in this study were
      divided into 3 groups depending on the log P(ow): 1<log P(ow)<2, 2<log P(ow)<3
      and 3<log P(ow). The adsorption amounts of above each group on the magnetite at
      an initial concentration of 100 ppm were 3.62 * 10(-3) (nitrobenzene), 1.92 * 10(
      2) (phenol), 1.13 * 10(-1) (chlorobenzene), 2.42 * 10(-1) (benzene), and 3.10 *
      10(-1)mmol/g (dichlorobenzene), respectively. This indicates that the adsorption
      behaviors depend on the strength of hydrophobicity of aromatic compounds. The
      adsorption mechanism for 2<log P(ow)<3 and 3<log P(ow) is hydrophobic interaction
      and that for 1<log P(ow)<2 is pi-electron interaction. The quantitative
      relationship between the amount of adsorbed compounds and modified functional
      groups and the fitting for adsorption isotherm models suggested that this
      adsorption might form a multi-layer adsorption in the most cases.

PMID- 21962864
TI  - Treatment of airborne asbestos and asbestos-like microfiber particles using
      atmospheric microwave air plasma.
AB  - Atmospheric microwave air plasma was used to treat asbestos-like microfiber
      particles that had two types of ceramic fiber and one type of stainless fiber.
      The treated particles were characterized via scanning electron microscopy (SEM)
      and X-ray diffraction (XRD). The experiment results showed that one type of
      ceramic fiber (Alumina:Silica=1:1) and the stainless fiber were spheroidized, but
      the other type of ceramic fiber (Alumina:Silica=7:3) was not. The conversion of
      the fibers was investigated by calculating the equivalent diameter, the aspect
      ratio, and the fiber content ratio. The fiber content ratio in various conditions
      showed values near zero. The relationship between the normalized fiber vanishing
      rate and the energy needed to melt the particles completely per unit surface area
      of projected particles, which is defined as eta, was examined and seen to
      indicate that the normalized fiber vanishing rate decreased rapidly with the
      increase in eta. Finally, some preliminary experiments for pure asbestos were
      conducted, and the analysis via XRD and phase-contrast microscopy (PCM) showed
      the availability of the plasma treatment.

PMID- 21962867
TI  - Enterococci as probiotics and their implications in food safety.
AB  - Enterococci belong to the lactic acid bacteria (LAB) and they are of importance
      in foods due to their involvement in food spoilage and fermentations, as well as
      their utilisation as probiotics in humans and slaughter animals. However, they
      are also important nosocomial pathogens that cause bacteraemia, endocarditis and
      other infections. Some strains are resistant to many antibiotics and possess
      virulence factors such as adhesins, invasins, pili and haemolysin. The role of
      enterococci in disease has raised questions on their safety for use in foods or
      as probiotics. Studies on the incidence of virulence traits among enterococcal
      strains isolated from food showed that some can harbour virulence traits, but it
      is also thought that virulence is not the result of the presence of specific
      virulence determinants alone, but is rather a more intricate process. Specific
      genetic lineages of hospital-adapted strains have emerged, such as E. faecium
      clonal complex (CC) 17 and E. faecalis CC2, CC9, CC28 and CC40, which are high
      risk enterococcal clonal complexes. These are characterised by the presence of
      antibiotic resistance determinants and/or virulence factors, often located on
      pathogenicity islands or plasmids. Mobile genetic elements thus are considered to
      play a major role in the establishment of problematic lineages. Although
      enterococci occur in high numbers in certain types of fermented cheeses and
      sausages, they are not deliberately added as starter cultures. Some E. faecium
      and E. faecalis strains are used as probiotics and are ingested in high numbers,
      generally in the form of pharmaceutical preparations. Such probiotics are
      administered to treat diarrhoea, antibiotic-associated diarrhoea or irritable
      bowel syndrome, to lower cholesterol levels or to improve host immunity. In
      animals, enterococcal probiotics are mainly used to treat or prevent diarrhoea,
      for immune stimulation or to improve growth. From a food microbiological point of
      view, the safety of the bacteria used as probiotics must be assured, and data on
      the major strains in use so far indicate that they are safe. The advantage of use
      of probiotics in slaughter animals, from a food microbiological point of view,
      lies in the reduction of zoonotic pathogens in the gastrointestinal tract of
      animals which prevents the transmission of these pathogens via food. The use of
      enterococcal probiotics should, in view of the development of problematic
      lineages and the potential for gene transfer in the gastrointestinal tract of
      both humans and animals, be carefully monitored, and the advantages of using
      these and new strains should be considered in a well contemplated risk/benefit
      analysis.

PMID- 21962865
TI  - Exploratory research to design a school nurse-delivered intervention to treat
      adolescent overweight and obesity.
AB  - OBJECTIVE: In preparation for a pilot study to evaluate the efficacy of a school
      nurse-delivered intervention, focus groups were conducted to gain insight into
      the perceptions of stakeholders regarding the design and implementation of the
      intervention. SETTING AND PARTICIPANTS: Fifteen focus groups at participating
      schools. One hundred subjects, including overweight and obese high school
      students, parents, high school nurses, and staff. MAIN OUTCOME MEASURE:
      Stakeholders' perceptions. ANALYSIS: Focus groups were audiotaped and transcribed
      verbatim. Theme instances related to the research aim were identified, coded, and
      sorted into theme categories. RESULTS: Major topics discussed included teen
      issues, family support, intervention implementation-related concerns, and
      curriculum content. Teen issues included dealing with peer pressure, avoiding
      emotional eating, and support from friends. Many participants thought it should
      be the teen's choice to involve parents. Confidentiality was the most commonly
      identified potential barrier to implementation. Recommendations for nutrition and
      physical activity curriculum content focused on concrete, practical strategies.
      CONCLUSIONS AND IMPLICATIONS: Results of this research provided insight into
      stakeholder's needs and perceptions regarding the content and structure of a
      school nurse-delivered intervention to treat adolescent overweight and obesity.
      Findings were used in the design and implementation of intervention protocols and
      materials.

PMID- 21962868
TI  - [The "double clock" or how to learn microsurgery without animal].
AB  - Animal experimentation is the most common way to learn microsurgery. However,
      this practice should be performed according to ethical rules and financial cost.
      This study has a triple aim: improving students' skills in microsurgery,
      respecting ethics and reducing costs by using fewer animals. We propose an
      ethical, practical and inexpensive training method that uses sewing needles. This
      training consists in microsurgery wire's passages in the eye of sewing needles
      arranged into circle. Specifically, 24 needles were arranged into two circles on
      a polystyrene block representing a "double clock". A specific scorecard for this
      exercise was made to evaluate the students. In total, between November 2010 and
      June 2011, fifteen residents followed the university degree in microsurgery
      provided by the faculty of medicine Henri Warembourg (Lille, France). The "double
      clock" was added to the eight already existing microsurgical manipulations. All
      of the participants were tested and this exercise was found to be effective as a
      teaching procedure. Also, each student used an average of 20 rats per year. This
      year we have reduced our animal control by 10% or about 30 rats. Our goals were
      achieved as we have improved student's microsurgical skills and also limiting
      cost by using fewer animals.

PMID- 21962869
TI  - [Sequelae of hand burns].
AB  - INTRODUCTION: Hand burns are common. Aesthetic and functional consequences are
      mixed together. ANATOMY: Palmar and dorsal skin are very different. Palmar skin
      is thick and strong, dedicated to the prehension. Dorsal skin is very thin,
      creating a mobility plan dedicated to the flexion of the fingers. AESTHETIC
      SEQUELAE: They are rarely isolated. Proximal nail retractions can occur after
      nail burns, with matricial exposition. We remove the scar and a full skin graft
      is done in order to give a normal proximal nail skin shape. FUNCTIONAL SEQUELAE:
      They are fingers and wrist retractions. We often use collagen substitute to cover
      soft tissue defect after scar excision. Commissure retractions are treated by
      trident plasty. PARTICULAR CASES: Electrical burns: we expose the case of a thumb
      amputation after necrosis by electrical burn, secondary treated by index
      policization. Children burns: the bridles appear during the growth, so we must
      follow this patient for a long time. CONCLUSION: Hand burns are frequent.
      Functional sequelae are often important: retractions, amputations. The
      orthopaedic treatment of these retractions is unspecific. We often use collagen
      substitute in our unit. The patient must be involved in his treatment, because it
      is very long and difficult.

PMID- 21962870
TI  - [Surgery of burn sequelae on the scalp].
AB  - Surgical treatment of scalp burn sequelae has achieved a decisive step with the
      use of tissue expansion. First, authors propose a brief recap on anatomy,
      physiopathology and usual surgical processes. Then they describe in details the
      tissue expansion and present some experimental results. As a conclusion, they
      discuss the learning curve associated with such a process.

PMID- 21962871
TI  - [Medico-legal assessment in the sequelae of burns (1st part)].
AB  - The assessment of physical injury in after-effects of burns is very specific.
      Indeed, the evolution of burn scars is particular compared to the scarring
      process in general. The expert needs to know these specific aspects in order to
      objectively assess the after-effects due to burns, in order to compensate for the
      loss of autonomy in major burn victims. The assessment has to analyze all the
      effects, functional and aesthetic, of the after-effects due to burns and has to
      particularly specify: the mending, which can never be set before one year, the
      pressure test allowing to check the complete maturation of the scars; the
      functional disability which results from skin retractions (due to after-effects)
      on the limbs mobility but which also must consider the burnt skin surface; the
      aesthetic damage, often important, with a discrimination between hypertrophic and
      keloid scars; the suffering, always significant in view of specialized and
      prolonged therapeutics; the sexual damage, often unrecognized in this type of
      injured people.

PMID- 21962872
TI  - How do index patients participating in genetic screening programmes for familial
      hypercholesterolemia (FH) interpret their DNA results? A UK-based qualitative
      interview study.
AB  - OBJECTIVE: To explore patients' interpretations of their DNA results for familial
      hypercholesterolemia (FH). METHODS: In-depth interviews were conducted with
      patients from two lipid clinics in Scotland, who were offered genetic testing as
      part of a nationwide cascade screening service. RESULTS: Patients were receptive
      to taking part in genetic screening and most expected a positive result.
      Receiving a molecular diagnosis of FH could provide reassurance to patients that
      diet and lifestyle factors were not the primary causes of their condition.
      Patients who received inconclusive results tended to interpret this as meaning
      that their high cholesterol was not genetic, which could induce feelings of
      uncertainty and self-blame. With the exception of newly diagnosed patients, for
      whom a positive result could provide a useful rationale for initiating statins,
      most perceived DNA screening to be of little relevance to their own medication
      use or their own approaches to lifestyle management. CONCLUSIONS: Index patients
      are likely to view DNA screening for FH as non-threatening. Receiving a positive
      DNA result can be reassuring for patients. Patients may not, however, interpret
      inconclusive DNA results correctly. PRACTICE IMPLICATIONS: Health professionals
      need to ensure FH index patients are prepared to receive, and fully understand,
      inconclusive DNA results.

PMID- 21962873
TI  - Discrete choice as a method for exploring education preferences in a Danish
      population of patients with type 2 diabetes.
AB  - OBJECTIVE: To determine preferences among patients with type 2 diabetes for
      content and format of patient education. METHODS: Using discrete choice methods,
      we surveyed patients about their preferences for patient education. We
      investigated preferred content and format regarding education on living well with
      diabetes, preventing complications, healthy eating, exercising, and psychosocial
      issues related to diabetes. RESULTS: We obtained usable responses from 2187
      patients with type 2 diabetes. Acquiring competencies to live a fulfilling life
      with diabetes, adjust diet and exercise habits, and prevent complications was
      significantly more highly valued than was simply being informed about these
      topics. Patients preferred to be involved in the planning of their diabetes care
      and valued individually tailored content higher than prescheduled content. Women
      and younger patients found diet and exercise significantly more important than
      did men, and patients with poorly controlled diabetes valued all education and
      support more highly than did patients in better control. CONCLUSION: Patients
      with type 2 diabetes prefer to be actively involved in educational activities, to
      develop competencies to prevent and manage complications, and to involve their
      social network in supporting them. PRACTICE IMPLICATIONS: Future patient
      education should enhance participation and competence development and include
      relatives.

PMID- 21962874
TI  - Paroxysmal non-kinesigenic dyskinesia due to a PNKD recurrent mutation: report of
      two Southern European families.
AB  - Paroxysmal non-kinesigenic dyskinesia (PNKD) is an autosomal dominant disorder
      characterized by attacks of dystonic or choreathetotic movements precipitated by
      stress, fatigue, coffee, alcohol or menstruation. In this report we present two
      families with PNKD of Southern European origin carrying a PNKD recurrent
      mutation. Incomplete penetrance and intrafamilial variability was detected in
      both families. Treatment with valproic acid and levetiracetam provided favorable
      response.

PMID- 21962875
TI  - Glut1 deficiency: when to suspect and how to diagnose?
AB  - Impaired glucose transport across the blood-brain barrier results in GLUT1
      deficiency syndrome (GLUT1-DS), characterized by infantile seizures,
      developmental delay, acquired microcephaly, spasticity, ataxia, and
      hypoglycorrhachia. A part from this classic phenotype, clinical conditions
      associated with a deficiency of GLUT1 are highly variable and several atypical
      variants have been described; in particular, patients with movement disorders,
      but without seizures, with paroxysmal exertion-induced dyskinesia, have been
      reported. Most patients carry heterozygous de novo mutations in the GLUT1-gene
      but autosomal dominant and recessive transmission has been identified. Diagnosis
      is based on low cerebrospinal fluid glucose, in the absence of hypoglycemia, and
      it is confirmed by molecular analysis of the GLUT1-gene and by glucose uptake
      studies and immunoreactivity in human erythrocytes. Treatment with a ketogenic
      diet results in marked improvement of seizures and movement disorders. This
      review summarizes recent advances in understanding of GLUT1-DS and highlights the
      diagnostic and therapeutic approach to GLUT1-DS.

PMID- 21962876
TI  - Limiting gifts, harming patients.

PMID- 21962877
TI  - SWL in lower calyceal calculi: evaluation of the treatment results in children
      and adults.
AB  - OBJECTIVE: To evaluate the treatment parameters of shockwave lithotripsy (SWL) in
      lower calyceal calculi in adults and children in a comparative manner. MATERIAL
      AND METHODS: Between 2006 and 2011, SWL was performed for lower calyceal calculi
      in 282 adults (mean age 48.5 years, range 28-64) and 54 children (mean age 48
      months, range 5-141). The Wolf Piezolith 3000 lithotriptor has been used for SWL.
      Success rates, auxiliary procedures, additional interventions, and complications
      were evaluated in detail in a comparative manner. RESULTS: Mean stone size was
      7.7 mm (range 5-25) and 8.1 mm (range 5-23) in children and in adults,
      respectively. Mean SWL sessions were 1.5 (range 1-5) in children and 2.4 (range 1
      6) in adults. Although 66.6% of children were stone-free after the first session,
      28% of adult patients were stone-free after the first SWL session, showing a
      statistically significant difference (P = .0001). After the treatments, although
      a complete stone-free status was obtained in 85% of children, 31.5% of adults
      were stone-free at 3-month follow-up after SWL (P = .0001). Although no auxiliary
      procedures were needed in children, 8.2% of adults required them. Likewise, the
      percentage of additional procedures were higher in adults than children (20.2%).
      CONCLUSION: SWL for lower calyceal calculi has been found to be highly successful
      in pediatric patients. These results demonstrate that, irrespective of stone
      size, SWL should be the first treatment alternative in the management of lower
      calyx stones in children.

PMID- 21962878
TI  - Lower urinary tract symptoms have negative associations with glomerular
      filtration rate irrespective of prostate volume in Korean men.
AB  - OBJECTIVE: To understand the relationship between lower urinary tract symptoms
      (LUTS) and renal function by prostate volume (PV) in Korean men. LUTS can be
      related to early renal dysfunction, irrespective of bladder outlet obstructive
      lesions, few studies have been conducted. METHODS: We conducted a cross-sectional
      survey of 3713 men, aged>=40 years, who received routine comprehensive health
      evaluations, including transrectal ultrasonography and the International Prostate
      Symptom Score questionnaire. We used the estimated glomerular filtration rate
      (GFR) for the assessment of renal function and the IPSS for LUTS severity. We
      compared LUTS and GFR using multivariate regression analysis after adjusting for
      age and/or PV. RESULTS: An increasing severity of LUTS, especially voiding LUTS,
      was associated with a decreasing GFR in the older age group (>=55 years). In a
      stratified analysis by PV of 30 cm3, voiding LUTS showed a negative association
      with GFR, irrespective of the PV (P for trend<.01 and P for trend<.02), but total
      LUTS did so only in the small PV group. CONCLUSION: In men without known urinary
      tract disease, LUTS and renal function had a negative association, especially in
      older men with a normal PV. Although the underlying mechanism is uncertain,
      physicians who treat patients with moderate or severe LUTS should monitor renal
      function, even in patients with a normal PV.

PMID- 21962879
TI  - Serum C-reactive protein levels are associated with residual urgency symptoms in
      patients with benign prostatic hyperplasia after medical treatment.
AB  - OBJECTIVE: Urinary urgency is a common and bothersome symptom in patients with
      benign prostatic hyperplasia (BPH); this symptom may persist even after medical
      treatment. Chronic inflammation has been reported to be associated with the
      pathogenesis of BPH and lower urinary tract symptoms (LUTS). We investigate the
      association between serum C-reactive protein (CRP) level and residual urgency
      symptoms in BPH patients after medical treatment. METHODS: Two-hundred-five men
      undergoing stable medical treatment for BPH, defined as a total prostate volume
      >=40 mL, were enrolled. Patients with acute infection or those taking nonsteroid
      antiinflammatory drugs or aspirin were excluded. Uroflowmetry, postvoid residual
      volume, transrectal ultrasound parameters, serum prostate specific antigen (PSA),
      and CRP level were measured. A three-day void diary was recorded to identify the
      presence of urinary urgency. RESULTS: The mean serum CRP level was 0.24 mg/dL
      (range 0.01-2.84), and residual urgency was identified in 90 patients (43.9%).
      Patients with residual urgency were older and had significantly higher serum CRP
      levels (0.39 +/- 0.54 mg/dL) than those without urgency (0.13 +/- 0.20, P <.001).
      On multivariable logistic regression analysis, men with CRP levels >=0.3 mg/dL
      were more likely to have urgency (odds ratio 8.08, 95% confidence interval 3.26
      20.0) after adjusting for age, serum PSA level, total prostate volume, and
      antimuscarinic use. Patients with serum CRP levels >=0.30 mg/dL had more urgency
      (82.1%) than those with serum CRP levels <0.30 mg/dL (34.9%). CONCLUSION: Serum
      CRP level is significantly associated with residual urgency in BPH patients after
      medical treatment. Chronic inflammation may play a role in the occurrence of
      residual urgency in BPH patients.

PMID- 21962880
TI  - Effect of sexually transmitted infections, lifetime sexual partner count, and
      recreational drug use on lower urinary tract symptoms in men who have sex with
      men.
AB  - OBJECTIVE: To investigate the relationship of lower urinary tract symptoms (LUTS)
      to urinary tract infection, prostatitis, sexually transmitted infection, lifetime
      sexual partner count, and recreational drug use in a population of men who have
      sex with men. LUTS in men are a source of considerable morbidity, distress, and
      medical expense. METHODS: We conducted a cross-sectional, Internet-based survey
      of urinary quality-of-life outcomes in men who have sex with men. The main
      outcome was the International Prostate Symptom Score (IPSS), classified as
      none/mild (IPSS 0-7), moderate/severe (IPSS 8-35), or severe (IPSS 20-35). The
      participants were also asked whether they ever sought medical attention for
      urinary problems. RESULTS: The survey web site was accessed by 2783 men, of whom
      2348 (84.3%) completed the questionnaire. The median age was 39 years (range 18
      81). Age, depression, human immunodeficiency virus infection, gonorrhea,
      syphilis, prostatitis, and prescription drug abuse were all associated with LUTS.
      Men who sought medical attention for LUTS were more likely to report older age,
      diabetes, depression, gonorrhea, urinary tract infection history, and
      prostatitis. CONCLUSION: Specific infectious conditions of the urinary tract and
      depressive symptoms are independent predictors of LUTS in men who have sex with
      men. Although LUTS are often multifactorial, a common unifying explanation for
      our finding could be the effects of local and systemic inflammation on the lower
      urinary tract.

PMID- 21962881
TI  - Sex-reversed acampomelic campomelic dysplasia with a homozygous deletion mutation
      in SOX9 gene.
AB  - Campomelic dysplasia (CD) is a rare autosomal dominant skeletal malformation with
      or without sex reversal. About 10% of cases that present with milder skeletal
      features are referred to as acampomelic campomelic dysplasia (ACD). CD and ACD
      are caused by mutations in SOX9. We report a patient of homozygous SOX9 deletion
      with minimal skeletal anomaly and female external genitalia in the presence of a
      male karyotype. The mechanisms explaining the homozygous deletion include a de
      novo mutation followed by gene conversion, uniparental disomy, or somatic
      crossing over. Our report highlights the possibility of ACD in XY sex-reversed
      patients with minimal skeletal presentation.

PMID- 21962882
TI  - Necroptosis: an emerging form of programmed cell death.
AB  - Necrosis plays an important role in multiple physiological and pathological
      processes. Recently, a relatively new form of necrosis has been characterized as
      "necroptosis". Morphologically, necroptosis exhibits the features of necrosis;
      however, necroptosis exhibits a unique signaling pathway that requires the
      involvement of receptor interaction protein kinase 1 and 3 (RIP1 and RIP3) and
      can be specifically inhibited by necrostatins. Necroptosis has been found to
      contribute to the regulation of immune system, cancer development as well as
      cellular responses to multiple stresses. In this review, we will summarize the
      signaling pathway, biological effects and pathological significance of this
      specific form of programmed cell death.

PMID- 21962883
TI  - Effects of N-acetyl-L-cysteine on fish hepatoma cells treated with mercury
      chloride and ionizing radiation.
AB  - Organisms are exposed to natural radiations from cosmic or terrestrial origins.
      Furthermore the combined action of radiation with various chemicals is an
      inevitable feature of modern life. Radiation is known to cause cell death, mainly
      due to its ability to produce reactive oxygen species in cells. N-acetyl-L
      cysteine (NAC) is a well-known sulfhydryl-containing antioxidant whose role in
      radioprotection has been reported. Synergistic effects of radiation and mercury
      chloride on human cells was previously reported by the authors. Based on the
      previous report, this study was designed to assess the synergistic effects of
      radiation and mercury chloride on fish hepatoma cells, as well as to investigate
      the protective effects of NAC on the cells. The cytotoxicity of radiation was
      enhanced in the presence of mercury chloride. NAC in lower concentrations
      prevented cells from death after irradiation with lower doses (<300 Gy) while it
      did not prevent cells from radiation-induced death after irradiation with higher
      doses (300, 500 Gy). The intracellular glutathione (GSH) levels significantly
      decreased after irradiation while the combined treatment of NAC and radiation
      alleviated the decrease in the GSH levels. The investigations give a clue for the
      action mechanism of synergistic or protective effects of NAC on the cells. Due to
      their high resistance to ionizing radiation, the PLHC-1 cells can be effectively
      used as a screening tool for assessing the combined effects of radiation with
      toxic chemicals.

PMID- 21962884
TI  - Permission to say "NO!".

PMID- 21962885
TI  - A case study using the beers list criteria to compare prescribing by family
      practitioners and geriatric specialists in a rural nursing home.
AB  - Previous studies have concluded that inappropriate medications and/or too many
      medications can lead to adverse events in older adults. The Beers List of
      potentially inappropriate medications (PIMs) for use in the elderly was developed
      to help guide clinicians to safely prescribe medications. Moreover, in the United
      States, policies exist regulating the number of prescriptions nursing home
      residents may take. Few studies have compared family and geriatric providers'
      prescribing trends. The aim of this study was to compare prescribing by family
      and geriatric providers in a rural U.S. nursing home using a nonequivalent 2
      group analysis design with data collected via retrospective chart audits (N=92).
      Nursing home residents in the nongeriatric provider group had fewer total
      comorbidities (U=p<.001) and were less likely to have congestive heart failure
      (chi2=p<.001), coronary artery disease (chi2=p<.001), and degenerative joint
      disease (chi2=p<.001). Despite this, on average, providers who were not geriatric
      trained prescribed twice as many drugs per patient (U=p<.001). The odds were
      significantly greater of being prescribed 9 or more drugs (odds ratio 13.15, 95%
      confidence interval 4.3-39.5) or being prescribed at least 1 PIM (odds ratio
      6.25, 95% confidence interval 1.3-29.0) if the prescriber was not geriatric
      trained. The prevalence in this nursing home of receiving at least 1 PIM and
      polypharmacy were 36.9% and 72.8%, respectively. Promethazine accounted for 46.9%
      of all PIMs prescribed. Geriatric education appears to have influenced
      prescribing patterns at this facility, with geriatric-trained providers adhering
      more closely to evidence-based guidelines for older patients. As geriatric
      educational content is incorporated into nongeriatric specialty areas,
      pharmacology and prescribing competencies should be an area of ongoing focus for
      educators.

PMID- 21962886
TI  - Focus on statin safety concerns.

PMID- 21962887
TI  - Department of labor guidance on teenager assistance in use of patient power
      lifts.

PMID- 21962888
TI  - Visceral prescription.

PMID- 21962889
TI  - Patient- and family-centered care--is there individualized care here?

PMID- 21962891
TI  - Which individuals undergoing BRACAnalysis need BART testing?
AB  - Deleterious mutations in BRCA1 and BRCA2 include those identified by sequencing
      technology as well as large genomic rearrangements (LGR). The main testing
      laboratory in the United States, Myriad Genetics Laboratory (MGL), has defined
      criteria for inclusion of LGR testing (i.e., BRACAnalysis Rearrangement Test, or
      BARTTM) when BRCA1 and BRCA2 testing is ordered. We were interested in
      determining how many of our patients with LGR mutations in BRCA1 and BRCA2
      fulfilled these MGL criteria. A retrospective chart review was performed on all
      individuals who underwent genetic testing at our institution since August 2006.
      Individuals who underwent LGR testing were classified as either having or not
      having a LGR in BRCA1 or BRCA2. Each individual's history was classified as
      meeting MGL defined LGR criteria, meeting criteria using third-degree relatives,
      or not meeting criteria. A total of 257 BART tests were ordered at our
      institution from August 2006 to August 2009. Five individuals (1.9%) had an LGR
      mutation. Two LGR were identified in patients who met MGL defined LGR criteria.
      One LGR was identified in a patient that met MGL defined LGR criteria only when
      using third-degree relatives. Two LGR were identified in individuals who did not
      meet MGL defined criteria. LGR are present in individuals who do not have a high
      pretest probability of carrying a mutation in BRCA1 or BRCA2. These data suggest
      that when BRCA1 and BRCA2 genetic testing is performed, testing should always
      include LGR testing so that the results are the most comprehensive and reliable.

PMID- 21962892
TI  - Molecular characterization of an EWSR1-POU5F1 fusion associated with a t(6;22) in
      an undifferentiated soft tissue sarcoma.
AB  - We report a soft tissue sarcoma from the thigh with morphologic features
      resembling Ewing sarcoma, clear cell sarcoma, and myoepithelial tumor of soft
      tissue. In addition, the genetic and immunohistochemical findings do not
      correspond to any established pattern, so the tumor does not clearly fit into any
      one classification. The karyotype analysis revealed a rare chromosomal
      rearrangement, t(6;22)(p22;q12), that previously has been reported in bone and
      epithelial tumors. Molecular studies confirmed the presence of an EWSR1-POU5F1
      fusion creating a chimeric gene with the N-terminal transcriptional activation
      domain of EWSR1 and the C-terminal POU DNA binding domain of POU5F1. This report
      is novel in that to our knowledge, it is the first complete molecular
      characterization of an EWSR1-POU5F1 fusion in a soft tissue sarcoma. Evaluation
      of existing data on the known EWSR1-POU5F1 tumors suggests that the fusion gene
      functions in a wide variety of cell types and may modify the differentiation
      state of cells, resulting in susceptibility to tumorigenesis.

PMID- 21962893
TI  - A single-center cytogenetic study of 629 Chinese patients with de novo acute
      myeloid leukemia--evidence of major ethnic differences and a high prevalence of
      acute promyelocytic leukemia in Chinese patients.
AB  - Cytogenetic information is important in the diagnosis, classification, and
      prognostication of acute myeloid leukemia (AML). Data obtained from multicenter
      treatment trials are well published. In this study, we contribute cytogenetic
      data from a large series of 629 Chinese patients with de novo AML that were
      karyotyped in a single laboratory. A higher prevalence of acute promyelocytic
      leukemia was observed when compared with non-Chinese series. The difference was
      most prominent in the younger age group. Abnormalities at chromosomal region
      11q23 and inv(16) seemed uncommon. These ethnic differences may indicate
      underlying genetic susceptibility to AML development and/or environmental
      differences. More comprehensive data on AML in the elder population are needed to
      assess the role of cytogenetics in predicting prognosis and guiding treatment in
      this large subgroup of patients.

PMID- 21962894
TI  - Comparison of methodologies for KRAS mutation detection in metastatic colorectal
      cancer.
AB  - Cetuximab and panitumumab are two monoclonal antibodies targeting the epidermal
      growth factor receptor that have been approved for treatment of metastatic
      colorectal cancer. Recent clinical trials found an association between KRAS
      mutation status and resistance to anti-epidermal growth factor receptor therapy,
      leading to the recommendation to perform KRAS mutation analysis before cetuximab
      or panitumumab treatment. This study was designed to compare and evaluate the
      efficacy of four different methodologies--high resolution melting, Sanger
      sequencing, DxS kit, and SNaPshot--for KRAS mutation detection in a clinical
      setting. In total, 372 samples from patients with metastatic colorectal cancer
      were analyzed by high resolution melting and SNaPshot, with 184 of those being
      further analyzed by Sanger sequencing and 188 with the DxS kit. Sensitivities
      were compared after consensus findings were determined by the presence of the
      same result in two of the three methodologies used in each case. The frequency of
      KRAS codon 12 and 13 mutations in our population was 43.5%, and a discordant
      finding was observed in 22 samples. Comparing to Sanger sequencing, significantly
      more consensus mutations were detected by the DxS kit (P=0.0139), high resolution
      melting (P=0.0004), and SNaPshot (P=0.00001), but no statistically significant
      differences were found among the three methodologies with higher sensitivity.

PMID- 21962896
TI  - Identification of chromosomal breakpoints of cancer-specific translocations by
      rolling circle amplification and long-distance inverse PCR.
AB  - We describe the use of rolling circle amplification and long-distance inverse
      polymerase chain reaction (LD-PCR) to identify chromosomal breakpoints and fusion
      genes in cancer cells carrying acquired translocations. This approach produced
      enough template for 100 inverse PCR reaction from as little as 20 ng of patient
      DNA, consequently enabling the use of up to 500 times less patient DNA compared
      to standard inverse PCR. The method is based on identifying restriction sites in
      a putative breakpoint area in a cancer-specific translocation, followed by
      circularization and amplification of the restriction DNA products by using T4 DNA
      ligase and Phi29 enzyme, respectively. The amplified DNA thus obtained is used as
      a template in long-distance inverse PCR to amplify and detect the precise
      breakpoint of the chromosomal rearrangements in question by sequencing of the
      obtained PCR products. We demonstrate the feasibility of this approach by
      identifying fusion genes TAF15-ZNF384 (brought about by a (12;17)(p13;q21)
      translocation) and BCR-ABL1 (produced by a (9:22)(q34;q11.2) translocation) in
      five leukemia samples. The application of rolling circle amplification before
      inverse PCR may be particularly useful in the search for chromosomal breakpoints
      and fusion genes brought about by new translocations when only minute amounts of
      DNA are available from the sampled malignant lesion.

PMID- 21962897
TI  - FOXP1 and PAX5 are rare but recurrent translocations partners in acute
      lymphoblastic leukemia.
AB  - Here, we report the case of a 57-year-old man, who was diagnosed with B-cell
      acute lymphoblastic leukemia (B-ALL). His diagnostic workup identified a
      translocation t(3;9)(p13;p13). This is the fifth case reported to date that
      involved the forkhead box P1 gene (FOXP1) and paired box gene 5 (PAX5). The PAX5
      FOXP1 translocation is a nonrandom aberration, which is recurrent in both
      childhood and in adult B-ALL, and may contribute to leukemogenesis by blocking
      differentiation of hematopoietic cells into mature B-cells.

PMID- 21962895
TI  - Long-range massively parallel mate pair sequencing detects distinct mutations and
      similar patterns of structural mutability in two breast cancer cell lines.
AB  - Cancer genomes frequently undergo genomic instability resulting in accumulation
      of chromosomal rearrangement. To date, one of the main challenges has been to
      confidently and accurately identify these rearrangements by using short-read
      massively parallel sequencing. We were able to improve cancer rearrangement
      detection by combining two distinct massively parallel sequencing strategies:
      fosmid-sized (36 kb on average) and standard 5 kb mate pair libraries. We applied
      this combined strategy to map rearrangements in two breast cancer cell lines,
      MCF7 and HCC1954. We detected and validated a total of 91 somatic rearrangements
      in MCF7 and 25 in HCC1954, including genomic alterations corresponding to
      previously reported transcript aberrations in these two cell lines. Each of the
      genomes contains two types of breakpoints: clustered and dispersed. In both cell
      lines, the dispersed breakpoints show enrichment for low copy repeats, while the
      clustered breakpoints associate with high copy number amplifications. Comparing
      the two genomes, we observed highly similar structural mutational spectra
      affecting different sets of genes, pointing to similar histories of genomic
      instability against the background of very different gene network perturbations.

PMID- 21962898
TI  - Paratesticular leiomyoma with a der(14)t(12;14)(q15;q24).
AB  - While uterine leiomyomas are among the most common and best cytogenetically
      characterized solid tumors, leiomyomas at other sites are rare. Only two
      karyotypically abnormal leiomyomas in males have been reported to date, both of
      them with unspecific chromosome aberrations. We recently analyzed by G-banding a
      paratesticular leiomyoma, a tumor type not cytogenetically examined before, and
      found the pseudodiploid karyotype
      46,XY,der(5)t(5;14)(q31;q24),der(14)t(12;14)(q15;q24). The leiomyoma cells
      demonstrated strong immunohistochemical nuclear expression of the HMGA2 protein,
      supporting a role of HMGA2 as the target gene in 12q14~15 rearrangements. In
      uterine leiomyomas, the t(12;14)(q15;q24) is the most frequent translocation
      leading to overexpression of HMGA2, therefore it seems that a common pathogenetic
      pathway exists for benign smooth muscle tumors of both the female and male
      reproductive organs. The finding of this abnormality may help identify a scrotal
      tumor of uncertain biologic potential but with smooth muscle differentiation as
      benign.

PMID- 21962899
TI  - Successful induction of oral tolerance in Netherton syndrome.

PMID- 21962900
TI  - Two flushing-like reaction cases from calcium pidolate who tolerated calcium
      carbonate.

PMID- 21962901
TI  - Eosinophilic activity and bronchial hyperresponsiveness within an asthmatic
      paediatric population.
AB  - BACKGROUND: Our study aims to assess the importance of serum eosinophil cationic
      protein (ECP) levels as a non-invasive marker of bronchial hyperresponsiveness
      (BHR) in children with asthma, and may predict objectively the asthmatic severity
      and sensitivities. METHODS: This study, which was carried out on 75 asthmatic
      patients from a paediatric population (average age: nine years old, sex-ratio
      M/F: 1.64), is based on both interrogation conducted by the clinician and
      biological explorations, essentially serological testing of ECP and eosinophilia
      determination, as well as the measurement of serological IgE amounts. RESULTS:
      The analysis of the questionnaires and the biological results allowed us to
      evaluate the clinico-biological relations within this population. ECP, more than
      eosinophilia, proves to be a relevant marker of asthma severity (p<0.05) and
      sensitivities within this given population (r=0.65). CONCLUSION: We were able to
      show that the evaluation of the serological levels of ECP seems to be a good
      biological marker of asthma.

PMID- 21962902
TI  - Cytokinin modulates endocytic trafficking of PIN1 auxin efflux carrier to control
      plant organogenesis.
AB  - Cytokinin is an important regulator of plant growth and development. In
      Arabidopsis thaliana, the two-component phosphorelay mediated through a family of
      histidine kinases and response regulators is recognized as the principal
      cytokinin signal transduction mechanism activating the complex transcriptional
      response to control various developmental processes. Here, we identified an
      alternative mode of cytokinin action that uses endocytic trafficking as a means
      to direct plant organogenesis. This activity occurs downstream of known cytokinin
      receptors but through a branch of the cytokinin signaling pathway that does not
      involve transcriptional regulation. We show that cytokinin regulates endocytic
      recycling of the auxin efflux carrier PINFORMED1 (PIN1) by redirecting it for
      lytic degradation in vacuoles. Stimulation of the lytic PIN1 degradation is not a
      default effect for general downregulation of proteins from plasma membranes, but
      a specific mechanism to rapidly modulate the auxin distribution in cytokinin
      mediated developmental processes.

PMID- 21962903
TI  - The tetraspanin CD63 regulates ESCRT-independent and -dependent endosomal sorting
      during melanogenesis.
AB  - Cargo sorting to intraluminal vesicles (ILVs) of multivesicular endosomes is
      required for lysosome-related organelle (LRO) biogenesis. PMEL-a component of
      melanocyte LROs (melanosomes)-is sorted to ILVs in an ESCRT-independent manner,
      where it is proteolytically processed and assembled into functional amyloid
      fibrils during melanosome maturation. Here we show that the tetraspanin CD63
      directly participates in ESCRT-independent sorting of the PMEL luminal domain,
      but not of traditional ESCRT-dependent cargoes, to ILVs. Inactivating CD63 in
      cell culture or in mice impairs amyloidogenesis and downstream melanosome
      morphogenesis. Whereas CD63 is required for normal PMEL luminal domain sorting,
      the disposal of the remaining PMEL transmembrane fragment requires functional
      ESCRTs but not CD63. In the absence of CD63, the PMEL luminal domain follows this
      fragment and is targeted for ESCRT-dependent degradation. Our data thus reveal a
      tight interplay regulated by CD63 between two distinct endosomal ILV sorting
      processes for a single cargo during LRO biogenesis.

PMID- 21962904
TI  - Evidence-based guideline recommendations on the use of positron emission
      tomography imaging in oesophageal cancer.
AB  - AIMS: To provide evidence-based practice guideline recommendations on the use of
      fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) for diagnosis,
      staging, assessing treatment response, liver metastasis and restaging or
      recurrence of oesophageal cancer. MATERIALS AND METHODS: A systematic review by
      Facey et al. (Health Technology Assessment 2007;11(44):iii-iv, xi-267) was used
      as the evidence base for recommendation development. As the review was limited to
      August 2005, the evidence base was updated to May 2010 using the same search
      strategies for MEDLINE and EMBASE used in the original review. The authors of the
      current systematic review drafted recommendations, which were reviewed, adapted
      and accepted by consensus by the Ontario provincial Gastrointestinal Disease Site
      Group and a special meeting of clinical experts. RESULTS: The results from the
      Facey et al. review for oesophageal cancer included four other systematic reviews
      and six primary studies. The 2005 to 2010 updated search included two additional
      systematic reviews and 29 primary studies. Recommendations were developed based
      on this evidence and accepted by consensus. CONCLUSIONS: PET is recommended to
      improve the accuracy of M staging for the staging work-up of patients with
      oesophageal cancer who are potential candidates for curative therapy. Due to
      insufficient evidence, no recommendation was made for or against the use of PET
      for the assessment of treatment response and the evaluation of suspected
      recurrence.

PMID- 21962906
TI  - Pulmonary hypertension adversely affects short- and long-term survival after
      mitral valve operation for mitral regurgitation: implications for timing of
      surgery.
AB  - OBJECTIVE: We investigated the impact of preoperative pulmonary hypertension (PH)
      on early and late outcomes after mitral valve operation for mitral regurgitation.
      METHODS: Systolic pulmonary artery pressure (sPAP) was measured before operation
      in 873 consecutive patients who underwent mitral valve surgery for mitral
      regurgitation between January 2002 and January 2010. PH was classified as none
      (sPAP < 40 mm Hg), mild (40 <= sPAP < 50 mm Hg), moderate (50 <= sPAP < 60 mm
      Hg), or severe (sPAP >= 60 mm Hg). RESULTS: Increased preoperative sPAP was
      associated with greater left ventricular dysfunction and dilation, left atrial
      enlargement, more atrial fibrillation, and tricuspid regurgitation. Operative
      mortality was correlated with the degree of preoperative PH (2%, 3%, 8%, and 12%
      for none, mild, moderate, and severe PH, respectively, P < .0001). Long-term
      survival was related to preoperative sPAP (5-year survival: 88%, 79%, 65%, and
      53% for none, mild, moderate, and severe PH, respectively; P < .0001). In
      multivariable analyses, sPAP was a predictor of both operative mortality (odds
      ratio, 1.023 per 1 mm Hg increase; 95% confidence interval, 1.003-1.044; P =
      .0270) and late death (hazard ratio, 1.018 per 1 mm Hg increase; 95% confidence
      interval, 1.007-1.028; P = .001). Among 284 patients with isolated degenerative
      mitral regurgitation due to leaflet prolapse, actuarial survival was 97.5%,
      91.2%, and 80.5% for none, mild, and moderate to severe PH, respectively (P =
      .0002). CONCLUSIONS: Preoperative sPAP is a powerful predictor of early and late
      survival after mitral valve operation for mitral regurgitation. Even modest
      increases in sPAP adversely affect outcomes. Mitral valve operation should be
      performed before the development of PH.

PMID- 21962907
TI  - Using the variability of continuous relative phase as a measure to discriminate
      between healthy and injured runners.
AB  - Several studies have used variability of continuous relative phase (CRP) to
      investigate overuse injuries, since low variability is thought to be related to
      running injuries. This study investigates whether the analysis of CRP variability
      leads to additional information about possible differences or similarities
      between healthy and injured runners. Further, a decision about future
      applications of CRP variability should be based on the ability to implement and
      interpret data. 18 healthy female runners (CO) and 18 female runners who suffered
      from iliotibial band syndrome (ITBS) were evaluated by calculating CRP
      variability for 4 coupling pairs. Besides analyzing continuous variability of
      CRP, we also averaged it for the whole stance phase and for four predefined
      stance phase intervals. Confidence intervals were displayed and independent t
      tests for comparing the two groups were conducted. During initial and terminal
      stance phase as well as after heel-off an increase in CRP variability was
      detected for both groups of runners. In contrast, the foot flat period was
      characterized by stable joint coordination and a decrease in variability. This
      paper presents possible interpretations of CRP variability but no statistically
      significant differences in CRP variability were found between the two groups of
      runners. Despite the missing statistical significance, a relationship between
      high CRP variability and injury seems to be conceivable, since the injured
      runners demonstrated an increased variability for all couplings in the first half
      of the stance phase. Further application of CRP variability in biomechanical
      research is essential to determine whether a relationship exists between injury
      and coordination variability.

PMID- 21962908
TI  - Survivorship of UKA in the middle-aged.
AB  - BACKGROUND: Unicompartmental knee arthroplasty (UKA) is known to be a viable
      procedure allowing for preservation of the intact compartments and delivering
      excellent function at long-term follow-up. The primary purpose of this single
      surgeon study was to analyse the survivorship of a fixed bearing UKA in patients
      younger than 60 years. METHODS: From all UKAs implanted between 1993 and 2005 at
      the senior authors' centre, 223 patients <60 years at operation with a minimum
      follow-up of 5 years were identified including all-poly and metal-backed tibiae.
      They were evaluated applying the Knee Society Score (KSS) at latest follow-up.
      Survivorship was calculated using Kaplan-Meier analysis, which considered the
      following variables: gender, type of tibial implant, medial vs. lateral UKA, and
      age. RESULTS: Average age at index operation was mean 53.7 (SD 5.8, range 30-60)
      years at a mean follow-up of 10.8 (SD 3.5, range 5-17) years. From the KSS, the
      knee score was 94.3 (SD 7.8) and the function score was 94.9 (SD 6.8). At latest
      follow-up, the implant survival rate was 94.3%. Survivorship for the entire
      cohort was 93.5% at 10 years (medial UKA 94.1% vs. lateral 91.8%), and 86.3% at
      15 years (85.1% medial vs. 91.7% lateral) CONCLUSION: In conclusion, excellent
      survival and function outcomes were noted in this subgroup of patients younger
      than 60 years. Revision rates were comparable to those studies in which UKA was
      performed on an elderly patient population. UKA can successfully be performed in
      patients younger than 60 years with appropriate patient selection.

PMID- 21962909
TI  - An efficient amplification pulse sequence for measuring chemical shift anisotropy
      under fast magic-angle spinning.
AB  - A two-dimensional experiment for measuring chemical shift anisotropy (CSA) under
      fast magic-angle spinning (MAS) is presented. The chemical shift anisotropy
      evolution is amplified by a sequence of pi-pulses that repetitively interrupt MAS
      averaging. The amplification generates spinning sideband manifolds in the
      indirect dimension separated by the isotropic shift along the direct dimension.
      The basic unit of the pulse sequence is designed based on the magic-angle turning
      experiment and can be concatenated for larger amplification factors.

PMID- 21962910
TI  - Low-field one-dimensional and direction-dependent relaxation imaging of bovine
      articular cartilage.
AB  - The structure of articular cartilage is separated into three layers of
      differently oriented collagen fibers, which is accompanied by a gradient of
      increasing glycosaminoglycan (GAG) and decreasing water concentration from the
      top layer towards the bone interface. The combined effect of these structural
      variations results in a change of the longitudinal and transverse relaxation
      times as a function of the distance from the cartilage surface. In this paper,
      this dependence is investigated at a magnetic field strength of 0.27 T with a one
      dimensional depth resolution of 50 MUm on bovine hip and stifle joint articular
      cartilage. By employing this method, advantage is taken of the increasing
      contrast of the longitudinal relaxation rate found at lower magnetic field
      strengths. Furthermore, evidence for an orientational dependence of relaxation
      times with respect to an axis normal to the surface plane is given, an
      observation that has recently been reported using high-field MRI and that was
      explained by preferential orientations of collagen bundles in each of the three
      cartilage zones. In order to quantify the extent of a further contrast mechanism
      and to estimate spatially dependent glycosaminoglycan concentrations, the data
      are supplemented by proton relaxation times that were acquired in bovine
      articular cartilage that was soaked in a 0.8 mM aqueous Gd++ solution.

PMID- 21962911
TI  - The mediating role of pain in substance use and depressive symptoms among
      Multicenter AIDS Cohort Study (MACS) participants.
AB  - Pain in human immunodeficiency virus (HIV) frequently co-occurs with substance
      use and depression. The complex associations among patient characteristics, pain,
      depression, and drug use in HIV suggests a role for testing models that can
      account for relationships simultaneously, control for HIV status, and also test
      for mediation. Using structural equation modeling, the current study examined
      associations among pain, sociodemographics, illicit drug use, and depressive
      symptoms in 921 HIV-seropositive and 1019 HIV-seronegative men from the
      Multicenter AIDS Cohort Study, an ongoing prospective study of the natural
      history of HIV infection among gay/bisexual men. Longitudinal repeated measures
      data collected over a 6-year period were analyzed using predictive path models in
      which sociodemographics, HIV status, and CD4+ cell counts predicted pain, which,
      in turn, predicted depressive symptoms and illicit drug use. The path models did
      not differ substantially between HIV-seropositive and -seronegative men. Analyses
      using the total sample indicated that pain served both as a mediator and as a
      predictor of more use of cannabis, cocaine, and heroin, as well as more
      depressive symptoms. HIV-seropositive status predicted more use of inhaled
      nitrites. In this cohort, having lower CD4+ cell counts (predicted by HIV
      status), being African American, less educated, and older were all associated
      with more pain, which, in turn, was associated with more illicit drug use and
      more depressive symptoms. The results underscore the need for adequate pain
      management, particularly among vulnerable subgroups of HIV-seropositive and HIV
      seronegative men to reduce the risk of drug use and depression.

PMID- 21962912
TI  - TRP-channel-specific cutaneous eicosanoid release patterns.
AB  - Analyzing mechanisms and key players in peripheral nociception nonneuronal skin
      cells are getting more and more into focus. Herein we investigated the functional
      expression of TRPV1 and TRPA1 in human keratinocytes and fibroblasts and assessed
      proinflammatory lipid mediator release upon their stimulation as well as sensory
      effects after topical application, combining in vitro and in vivo approaches. In
      vitro, the expression of functional TRPV1 and TRPA1 channels on fibroblasts and
      keratinocytes was confirmed via immunofluorescence, qualitative real time (RT)
      polymerase chain reaction, and cellular Ca(2+) influx measurements. Additionally,
      the agonists allyl isothiocyanate (TRPA1) and capsaicin (TRPV1) induce a
      differential secretion pattern of the eicosanoids PGE(2) and LTB(4) in human
      dermal fibroblasts and keratinocytes, which was also detectable invivo, analyzing
      suction blister fluid at various times after short-term topical application.
      Capsaicin provoked the release of LTB(4) at 2 and 24 hours. In contrast, PGE(2)
      levels were reduced upon stimulation. Allyl isothiocyanate, however, increased
      PGE(2) levels only at 24 hours, but did not alter LTB(4) levels. In parallel,
      heat pain thresholds were reduced by both agents after short-term topical
      application, but only AITC provoked a long-lasting local erythema. In conclusion,
      the agonist-induced activation of nociceptors by TRPA1 and TRPV1 elicits painful
      sensations, whereas nonneuronal tissue cells respond with differential release of
      inflammatory mediators, thus influencing local vasodilatation and neuronal
      sensitization. These results have implications for the application of transient
      receptor potential antagonists to improve inflammatory skin conditions and pain
      management.

PMID- 21962913
TI  - Perinatal phencyclidine treatment alters neuregulin 1/erbB4 expression and
      activation in later life.
AB  - Schizophrenia is a complex and devastating mental disorder of unknown etiology.
      Hypofunction of N-methyl-D-aspartate (NMDA) receptors are implicated in the
      disorder, since phencyclidine (PCP) and other NMDA receptor antagonists mimic
      schizophrenia-like symptoms in humans and animals so well. Moreover, genetic
      linkage and post mortem studies strongly suggest a role for altered neuregulin 1
      (Nrg1)/erbB4 signaling in schizophrenia pathology. This study investigated the
      relationship between the NMDA receptor and Nrg1 signaling pathways using the
      perinatal PCP animal model. Rats (n=5/group) were treated with PCP (10 mg/kg) or
      saline on postnatal days (PN) 7, 9 and 11 and were sacrificed on PN12, 5 weeks
      and 20 weeks for biochemical analyses. Western blotting was used to determine
      total and phosphorylated levels of proteins involved in NMDA receptor/Nrg1
      signaling in the prefrontal cortex and hippocampus. In the cortex, PCP treatment
      altered Nrg1/erbB4 expression levels throughout development, including decreased
      Nrg1 and erbB4 at PN12 (-25-30%; p<0.05); increased erbB4 and p-erbB4 (+18-27%;
      p<0.01) at 5 weeks; and decreased erbB4 and p-erbB4 (-16-18%; p<0.05) along with
      increased Nrg1 (+33%; p<0.01) at 20 weeks. In the hippocampus, levels of
      Nrg1/erbB4 were largely unaffected apart from a significant decrease in p-erbB4
      at 20 weeks (-13%; p<0.001); however NMDA receptor subunits and PSD-95 showed
      increases at PN12 and 5 weeks (+20-32%; p<0.05), and decreases at 20 weeks (-22
      29%; p<0.05). This study shows that NMDA receptor antagonism early in development
      can have long term effects on Nrg1/erbB4 expression which could be important in
      understanding pathological processes which might be involved in schizophrenia.

PMID- 21962914
TI  - The effects of oxytocin and its analog, carbetocin, on genetic deficits in
      sensorimotor gating.
AB  - Converging evidence from preclinical and clinical studies suggest that oxytocin
      has therapeutic potential for schizophrenia and other neuropsychiatric disorders.
      Prepulse inhibition of the startle reflex (PPI) is a measure of sensorimotor
      gating, an important brain function involved in filtering environmental
      information. We previously demonstrated that systemically administered oxytocin
      reversed psychostimulant-induced PPI deficits in rats suggesting that oxytocin
      can produce antipsychotic-like central effects. That finding was supported by a
      recent trial in humans, which found that intranasal oxytocin reduced symptoms of
      schizophrenia. The goal of this study was to extend this line of investigation by
      testing the effects of oxytocin, and a structural analog of oxytocin, carbetocin,
      on non-pharmacological deficits in PPI. In experiment 1, Brown Norway (BN) rats,
      a rat strain that has naturally low PPI, were given either saline or one of three
      doses of oxytocin (0.04-1.0 mg/kg, sc). In experiment 2, BN rats were given
      either saline, one of three doses of carbetocin (0.04-1.0 mg/kg) or oxytocin (1
      mg/kg). PPI and acoustic startle response (ASR) of rats were tested. Oxytocin
      significantly increased PPI (P<0.01) and decreased ASR levels (P<0.01) in BN rats
      in a dose-dependent fashion. In contrast, carbetocin had no effect on PPI levels
      or ASR. The facilitation of BN PPI by oxytocin is similar to what we have
      previously observed with clozapine and thus further supports oxytocin having
      antipsychotic properties. In contrast to oxytocin, our data do not support the
      use of carbetocin as an antipsychotic drug.

PMID- 21962915
TI  - Neuropathological abnormalities of astrocytes, GABAergic neurons, and pyramidal
      neurons in the dorsolateral prefrontal cortices of patients with major depressive
      disorder.
AB  - Human post-mortem brain studies have revealed reduced density and size of neurons
      and glial cells in the dorsolateral prefrontal cortex (dlPFC) in major depressive
      disorder (MDD). However, the basis of these cytoarchitectural abnormalities and
      the relationship between them are not understood. We hypothesized that the
      reduced density of GABAergic neurons and glial cells was associated with altered
      glutamate neurotransmission in the dlPFC. In order to test this hypothesis, we
      examined a specific marker type (i.e., calretinin, CR: as a marker of GABAergic
      neurons) and also attempted to identify the neuropathological markers that
      correlate with the density of CR-immunoreactive (IR) GABAergic neurons in the
      dlPFC, using the Stanley Neuropathology Consortium Integrative Database (SNCID,
      http://sncid.stanleyresearch.org/), which is a web-based tool used to integrate
      Stanley Medical Research Institute (SMRI) data sets. We found that the density of
      CR-IR GABAergic neurons was significantly lower in layer I of the dlPFC of MDD
      patients (n=15) than in that of unaffected controls (n=15) (p=0.021). CR-IR
      GABAergic neuronal changes were positively correlated with changes in several
      markers for glial cells and pyramidal neurons in the dlPFC of all SNC subjects
      (n=60). We also found that the glutamate changes negatively correlated with glial
      fibrillary acidic protein (GFAP) expression levels and CR-IR GABAergic neuronal
      density in the prefrontal cortex of all SNC subjects (P<0.05). These findings
      yield some insight into the mechanism by which increased glutamatergic
      neurotransmission leads to excitotoxic damage both in neurons and glial cells in
      the dlPFC of MDD patients.

PMID- 21962916
TI  - Automated sperm head morphology analyzer for open-source software.
AB  - Sperm head morphology has been identified as a characteristic that can be used to
      predict a male's semen quality. In the present study, we have developed an
      automated sperm head morphology analysis (ASMA) plug-in for open-source ImageJ
      software (http://rsbweb.nih.gov/ij/). We describe the plug-in's functionality,
      and confirm its validity for sperm head morphology analysis using fish sperm.
      Sperm head morphological measurements (length and width) made with the ASMA plug
      in did not differ from manual measurements. Using the plug-in to measure sperm
      head-shaped objects of known size, the associated plug-in error rate was < 0.5%.
      Brightness and contrast ratios influenced sperm head measurements, suggesting the
      need for standardized protocols. This plug-in was effective at measuring
      elliptical (i.e., Atlantic cod) as well as slightly irregular (i.e., Chinook
      salmon) shaped sperm heads. In conclusion, our ASMA plug-in represents a
      versatile alternative to costly sperm morphology software.

PMID- 21962917
TI  - Regularising limited view tomography using anatomical reference images and
      information theoretic similarity metrics.
AB  - This paper is concerned with limited view tomography. Inspired by the application
      of digital breast tomosynthesis (DBT), which is but one of an increasing number
      of applications of limited view tomography, we concentrate primarily on cases
      where the angular range is restricted to a narrow wedge of approximately +/-30
      degrees , and the number of views is restricted to 10-30. The main challenge
      posed by these conditions is undersampling, also known as the null space problem.
      As a consequence of the Fourier Slice Theorem, a limited angular range leaves
      large swathes of the object's Fourier space unsampled, leaving a large space of
      possible solutions, reconstructed volumes, for a given set of inputs. We explore
      the feasibility of using same- or different-modality images as anatomical priors
      to constrain the null space, hence the solution. To allow for different-modality
      priors, we choose information theoretic measures to quantify the similarity
      between reconstructions and their priors. We demonstrate the limitations of two
      popular choices, namely mutual information and joint entropy, and propose robust
      alternatives that overcome their limitations. One of these alternatives is
      essentially a joint mixture model of the image and its prior. Promising
      mitigation of the data insufficiency problem is demonstrated using 2D synthetic
      as well as clinical phantoms. This work initially assumes a priori registered
      priors, and is then extended to allow for the registration to be performed
      simultaneously with the reconstruction.

PMID- 21962918
TI  - Direct lineage conversion of terminally differentiated hepatocytes to functional
      neurons.
AB  - Several recent studies have showed that mouse and human fibroblasts can be
      directly reprogrammed into induced neuronal (iN) cells, bypassing a pluripotent
      intermediate state. However, fibroblasts represent heterogeneous mesenchymal
      progenitor cells that potentially contain neural crest lineages, and the cell of
      origin remained undefined. This raises the fundamental question of whether
      lineage reprogramming is possible between cell types derived from different germ
      layers. Here, we demonstrate that terminally differentiated hepatocytes can be
      directly converted into functional iN cells. Importantly, single-cell and genome
      wide expression analyses showed that fibroblast- and hepatocyte-derived iN cells
      not only induced a neuronal transcriptional program, but also silenced their
      donor transcriptome. The remaining donor signature decreased over time and could
      not support functional hepatocyte properties. Thus, the reprogramming factors
      lead to a binary lineage switch decision rather than an induction of hybrid
      phenotypes, but iN cells retain a small but detectable epigenetic memory of their
      donor cells.

PMID- 21962919
TI  - Conservative management of nontubal ectopic pregnancies.
AB  - OBJECTIVE: To report successful conservative management of nontubal ectopic
      pregnancies. DESIGN: Retrospective case series. SETTING: University tertiary-care
      hospital. PATIENT(S): Sixty-four women with diagnosis of nontubal ectopic
      pregnancies (cervical, cornual, and cesarean section scar) were treated with
      minimally invasive procedures. INTERVENTION(S): Systemic methotrexate alone or
      combined with ultrasound-guided fetal intracardiac injection of potassium
      chloride. MAIN OUTCOME MEASURE(S): Success of the treatment, preservation of the
      uterus, rate of serious complications, and the need for additional interventions.
      RESULT(S): Conservative treatment was successful in 63 patients with nontubal
      ectopic pregnancies. One patient had rupture of cornual pregnancy and underwent
      cornual resection. None of the patients in this case series required
      hysterectomy. This series included four patients with heterotopic pregnancies,
      three of whom continued intrauterine pregnancy to term gestation after
      conservative treatment. Seven patients experienced minimal morbidity that was
      treated with additional nonsurgical interventions. CONCLUSION(S): Conservative
      management and fertility preservation is feasible in most nontubal ectopic
      pregnancies.

PMID- 21962920
TI  - Effects of chlorpyrifos on cholinesterase activity and stress markers in the
      tropical reef fish Acanthochromis polyacanthus.
AB  - Tropical coastal ecosystems, including the Great Barrier Reef (GBR) of Australia
      are increasingly threatened by pollution; yet few studies have investigated the
      sensitivity of GBR species to these pollutants. Here we exposed juveniles of the
      tropical reef fish Acanthochromis polyacanthus (spiny damselfish) to three
      concentrations of the insecticide chlorpyrifos (CPF) and measured (i) muscle
      cholinesterase (ChE) activity; (ii) hepatic glutathione-S-transferase (GST)
      activity; and (iii) coenzyme Q (CoQ) redox balance, after 6h and 96h of exposure.
      After 96h, muscle ChE activity was significantly inhibited by 26%, 49% and 53%
      when fish were exposed to 1, 10 or 100MUg/L CPF, respectively. Muscle ChE
      characterization revealed three types of ChEs, including two atypical forms.
      Hepatic CoQ antioxidant form significantly increased at 10MUg/L after 6h of
      exposure, potentially demonstrating an early response to CPF-induced oxidative
      stress in liver. Hepatic GST was not affected by CPF exposure.

PMID- 21962921
TI  - Spatial and temporal changes in microbial diversity of the Marmara Sea sediments.
AB  - Spatial (10 different locations) and temporal (2 years) changes in
      characteristics of the Marmara Sea Sediments were monitored to determine
      interactions between the chemical and microbial diversity. The sediments were
      rich in terms of hydrocarbon, nitrate, Ni and microbial cell content.
      Denitrifying, sulfate reducing, fermentative and methanogenic organisms were co
      abundant in 15 cm below the sea floor. The local variations in the sediments'
      characteristics were more distinctive than the temporal ones. The sulfate and
      nitrate contents were the main drivers of the changes in the microbial community
      compositions. N and P were limited for microbial growth in the sediments, and
      their levels determined the total cell abundance and activity. Seasonal shifts in
      temperatures of the shallow sediments were also reflected in the active cell
      abundances. It was concluded that the Marmara Sea is a promising ecosystem for
      the further investigation of the ecologically important microbial processes.

PMID- 21962922
TI  - Evaluation of sewage source and fate on southeast Florida coastal reefs.
AB  - Water, sponge and coral samples were collected from stations impacted by a
      variety of pollution sources and screened for human enteric viruses as
      conservative markers for human sewage. While human enteroviruses and adenoviruses
      were not detected, noroviruses (NoV; human genogroups I and II) were detected in
      31% of samples (especially in sponge tissue). Stations near inlets were the only
      ones to show multiple sample types positive for NoV. Fecal indicator bacteria and
      enteric viruses were further evaluated at multiple inlet stations on an outgoing
      tide. Greatest indicator concentrations and highest prevalence of viruses were
      found at the mouth of the inlet and offshore in the inlet plume. Results suggest
      that inlets moving large volumes of water into the coastal zone with tides may be
      an important source of fecal contaminants. Efforts to reduce run-off or
      unintended release of water into the Intracoastal Waterway may lower contaminants
      entering sensitive coastal areas.

PMID- 21962923
TI  - Somatic mutations in exon 17 of the TEK gene in vascular tumors and vascular
      malformations.
AB  - OBJECTIVE: As a common disease, the molecular etiology of noninherited vascular
      anomalies is still poorly understood. Recently, somatic mutations in exon 17 of
      the endothelial cell tyrosine kinase receptor Tie-2 (encoded by TEK) were
      identified in 49.1% of patients with common sporadic venous malformation, a
      subtype of vascular anomalies. We assessed whether such a mutational region also
      had a role in the Chinese population or in other subtypes of noninherited
      vascular anomalies (vascular tumors and vascular malformations). METHODS: Direct
      sequencing of polymerase chain reaction (PCR)-amplified DNA, extracted from 139
      lesions in 129 individuals with noninherited vascular anomalies (vascular tumors
      or vascular malformations) and 60 control samples, was used for detecting the
      mutations in exon 17 of the TEK gene. Mutations were confirmed by allele-specific
      PCR. Clone sequences were then used for the mutations identified for the first
      time. We also explored the associations between these mutations and clinical
      characteristics (gender, onset age, number of lesions, severity, category, and
      recurrence of the disease) in both vascular tumors and vascular malformations.
      RESULTS: Two somatic TEK mutations (Y897C, R915C) were identified in vascular
      tumors, and seven somatic TEK mutations (Y897H, Y897C, L914F, R915C, S917I,
      R918C, R918H) were identified in vascular malformations. Among these mutations,
      R918C (2,752 C > T) and R918H (2,753 G > A) were first identified in noninherited
      vascular anomalies. Somatic TEK mutations were detected in lesions from 4 of 23
      (17.4%) vascular tumors and 35 of 106 (33.0%) vascular malformations, where most
      mutations were single substitutions in vascular tumors (100%) and vascular
      malformations (88.6%), while the remainders were double substitutions. In
      addition to the reported venous malformation, such mutations were identified in
      some other subtypes of vascular anomalies, including vascular tumors (infantile
      hemangioma, pyogenic granuloma, and epithelioid hemangioma) and vascular
      malformations (capillary malformation, arteriovenous malformation, capillary
      lymphatic malformation, and capillary arteriovenous malformation). By contrast,
      these mutations were absent from the control tissues or blood. However, mutations
      showed no association (P > .05) with clinical characteristics in vascular
      anomalies or either of its two types (vascular tumors or vascular malformations).
      CONCLUSIONS: Our study revealed that somatic mutations in exon 17 of the TEK gene
      were more common in noninherited vascular anomalies than previously reported.
      Furthermore, such substitutions may shed new light on the molecular etiology,
      diagnosis, and potential therapeutic targets of vascular anomalies.

PMID- 21962924
TI  - Defining the type of surgeon volume that influences the outcomes for open
      abdominal aortic aneurysm repair.
AB  - OBJECTIVE: Prior studies have reported improved clinical outcomes with higher
      surgeon volume, which is assumed to be a product of the surgeon's experience with
      the index operation. We hypothesized that composite surgeon volume is an
      important determinant of outcome. We tested this hypothesis by comparing the
      impact of operation-specific surgeon volume versus composite surgeon volume on
      surgical outcomes, using open abdominal aortic aneurysm (AAA) repair as the index
      operation. METHODS: The Nationwide Inpatient Sample was analyzed to identify
      patients undergoing open AAA repairs for 2000 to 2008. Surgeons were stratified
      into deciles based on annual volume of open AAA repairs ("operation-specific
      volume") and overall volume of open vascular operations ("composite volume").
      Composite volume was defined by the sum of several open vascular operations:
      carotid endarterectomy, aortobifemoral bypass, femoral-popliteal bypass, and
      femoral-tibial bypass. Multiple logistic regression analyses were used to examine
      the relationship between surgeon volume and in-hospital mortality for open AAA
      repair, adjusting for both patient and hospital characteristics. RESULTS: Between
      2000 and 2008, an estimated 111,533 (95% confidence interval [CI], 102,296
      121,232) elective open AAA repairs were performed nationwide by 6,857 surgeons.
      The crude in-hospital mortality rate over the study period was 6.1% (95% CI, 5.6%
      6.5%). The mean number of open AAA repairs performed annually was 2.4 operations
      per surgeon. The mean composite volume was 5.3 operations annually. As expected,
      in-hospital mortality for open AAA repair decreased with increasing volume of
      open AAA repairs performed by a surgeon. Mortality rates for the lowest and
      highest deciles of surgeon volume were 10.2% and 4.5%, respectively (P < .0001).
      A similar pattern was observed for composite surgeon volume, as the mortality
      rates for the lowest and highest deciles of composite volume were 9.8% and 4.8%,
      respectively (P < .0001). After adjusting for patient and hospital
      characteristics, increasing composite surgeon volume remained a significant
      predictor of lower in-hospital mortality for open AAA repair (odds ratio, 0.994;
      95% CI, .992-.996; P < .0001), whereas increasing volume of AAA repairs per
      surgeon did not predict in-hospital deaths. CONCLUSIONS: The current study
      suggests that composite surgeon volume-not operation-specific volume-is a key
      determinant of in-hospital mortality for open AAA repair. This finding needs to
      be considered for future credentialing of surgeons.

PMID- 21962925
TI  - Evaluation of cold storage conditions for vessels obtained from donor rats after
      cardiac death.
AB  - OBJECTIVE: To improve the availability of vessel grafts for allotransplantation,
      the current experimental study was designed to first investigate the function of
      vessels obtained from non-heartbeating donor rats at various time points
      postmortem; second, to assess the sensitivity of vessels recovered after
      circulatory arrest toward prolonged cold storage; and third, to determine vessel
      function following cold storage with antimicrobial additives. METHODS: We
      investigated vessel tone development and endothelium-dependent and endothelium
      independent relaxations in a Mulvany myograph of aorta and saphenous artery
      sampled up to 24 hours after circulatory arrest. Additionally, tissue reductive
      capacity and lactate dehydrogenase release were measured. RESULTS: Vessels
      recovered 2 hours postmortem showed similar results as controls recovered without
      delay. Vessels recovered 6 hours or more after circulatory arrest showed reduced
      vessel tone development (ie, aorta): response to potassium <15% and response to
      norepinephrine <25% of vessels recovered without delay; A. saphena response to
      potassium: <12% and response to norepinephrine <10% of control vessels recovered
      without delay. All vessels recovered after circulatory arrest showed a similar
      cold storage sensitivity as controls, with exception of a decreased endothelial
      function of A. saphena harvested 6 hours postmortem (one-third response of non
      stored control vessels). Treatment of vessels recovered immediately or after
      circulatory arrest with gentamycin, piperacillin, and metronidazole as additives
      to the optimized cold storage solution did not alter vessel function.
      Flucloxacillin as a cold storage additive reduced vessel tone development in
      aorta but not in A. saphena. Addition of amphotericin B to the storage solution
      completely abolished any vessel function and impaired tissue reductive capacity
      despite presence of radical scavengers. CONCLUSIONS: The use of vessels from non
      heartbeating donors in general and subsequent prolonged cold storage seems
      feasible when vessels are recovered within 2 hours. The use of antibiotics needs
      to be carefully assessed for each intended-to-use tissue. For vessels tested, a
      combination of gentamycin, piperacillin, and metronidazole supported the
      maintenance of vessel function.

PMID- 21962926
TI  - Validation of Venous Clinical Severity Score (VCSS) with other venous severity
      assessment tools from the American Venous Forum, National Venous Screening
      Program.
AB  - BACKGROUND: Several standard venous assessment tools have been used as
      independent determinants of venous disease severity, but correlation between
      these instruments as a global venous screening tool has not been tested. The
      scope of this study is to assess the validity of Venous Clinical Severity Scoring
      (VCSS) and its integration with other venous assessment tools as a global venous
      screening instrument. METHODS: The American Venous Forum (AVF), National Venous
      Screening Program (NVSP) data registry from 2007 to 2009 was queried for
      participants with complete datasets, including CEAP clinical staging, VCSS,
      modified Chronic Venous Insufficiency Quality of Life (CIVIQ) assessment, and
      venous ultrasound results. Statistical correlation trends were analyzed using
      Spearman's rank coefficient as related to VCSS. RESULTS: Five thousand eight
      hundred fourteen limbs in 2,907 participants were screened and included CEAP
      clinical stage C0: 26%; C1: 33%; C2: 24%; C3: 9%; C4: 7%; C5: 0.5%; C6: 0.2%
      (mean, 1.41 +/- 1.22). VCSS mean score distribution (range, 0-3) for the entire
      cohort included: pain 1.01 +/- 0.80, varicose veins 0.61 +/- 0.84, edema 0.61 +/-
      0.81, pigmentation 0.15 +/- 0.47, inflammation 0.07 +/- 0.33, induration 0.04 +/-
      0.27, ulcer number 0.004 +/- 0.081, ulcer size 0.007 +/- 0.112, ulcer duration
      0.007 +/- 0.134, and compression 0.30 +/- 0.81. Overall correlation between CEAP
      and VCSS was moderately strong (r(s) = 0.49; P < .0001), with highest correlation
      for attributes reflecting more advanced disease, including varicose vein (r(s) =
      0.51; P < .0001), pigmentation (r(s) = 0.39; P < .0001), inflammation (r(s) =
      0.28; P < .0001), induration (r(s) = 0.22; P < .0001), and edema (r(s) = 0.21; P
      < .0001). Based on the modified CIVIQ assessment, overall mean score for each
      general category included: Quality of Life (QoL)-Pain 6.04 +/- 3.12 (range, 3
      15), QoL-Functional 9.90 +/- 5.32 (range, 5-25), and QoL-Social 5.41 +/- 3.09
      (range, 3-15). Overall correlation between CIVIQ and VCSS was moderately strong
      (r(s) = 0.43; P < .0001), with the highest correlation noted for pain (r(s) =
      0.55; P < .0001) and edema (r(s) = 0.30; P < .0001). Based on screening venous
      ultrasound results, 38.1% of limbs had reflux and 1.5% obstruction in the
      femoral, saphenous, or popliteal vein segments. Correlation between overall
      venous ultrasound findings (reflux + obstruction) and VCSS was slightly positive
      (r(s) = 0.23; P < .0001) but was highest for varicose vein (r(s) = 0.32; P <
      .0001) and showed no correlation to swelling (r(s) = 0.06; P < .0001) and pain
      (r(s) = 0.003; P = .7947). CONCLUSIONS: While there is correlation between VCSS,
      CEAP, modified CIVIQ, and venous ultrasound findings, subgroup analysis indicates
      that this correlation is driven by different components of VCSS compared with the
      other venous assessment tools. This observation may reflect that VCSS has more
      global application in determining overall severity of venous disease, while at
      the same time highlighting the strengths of the other venous assessment tools.

PMID- 21962927
TI  - Sustainable microbial water quality monitoring programme design using phage-lysis
      and multivariate techniques.
AB  - Contamination of surface waters is a pervasive threat to human health, hence, the
      need to better understand the sources and spatio-temporal variations of
      contaminants within river catchments. River catchment managers are required to
      sustainably monitor and manage the quality of surface waters. Catchment managers
      therefore need cost-effective low-cost long-term sustainable water quality
      monitoring and management designs to proactively protect public health and
      aquatic ecosystems. Multivariate and phage-lysis techniques were used to
      investigate spatio-temporal variations of water quality, main polluting
      chemophysical and microbial parameters, faecal micro-organisms sources, and to
      establish 'sentry' sampling sites in the Ouse River catchment, southeast England,
      UK. 350 river water samples were analysed for fourteen chemophysical and
      microbial water quality parameters in conjunction with the novel human-specific
      phages of Bacteroides GB-124 (Bacteroides GB-124). Annual, autumn, spring,
      summer, and winter principal components (PCs) explained approximately 54%, 75%,
      62%, 48%, and 60%, respectively, of the total variance present in the datasets.
      Significant loadings of Escherichia coli, intestinal enterococci, turbidity, and
      human-specific Bacteroides GB-124 were observed in all datasets. Cluster analysis
      successfully grouped sampling sites into five clusters. Importantly, multivariate
      and phage-lysis techniques were useful in determining the sources and spatial
      extent of water contamination in the catchment. Though human faecal contamination
      was significant during dry periods, the main source of contamination was non
      human. Bacteroides GB-124 could potentially be used for catchment routine
      microbial water quality monitoring. For a cost-effective low-cost long-term
      sustainable water quality monitoring design, E. coli or intestinal enterococci,
      turbidity, and Bacteroides GB-124 should be monitored all-year round in this
      river catchment.

PMID- 21962928
TI  - Predicting stream N and P concentrations from loads and catchment characteristics
      at regional scale: a concentration ratio method.
AB  - We used a concentration ratio method to predict yearly and summer averages of
      stream total nitrogen, nitrate and total phosphorus concentrations at a regional
      scale. The ratio of the median daily concentration on the flow weighted annual
      concentration was used. This ratio characterizes the concentration dynamics of a
      catchment. We took advantage of the commonly used budget type models applied at a
      regional scale to relate concentrations to loads instead of directly to land
      uses, as has previously been done. The relationship was modeled with Boosted
      Regression Trees using catchment and stream characteristics along with loads and
      flows obtained from the SPARROW budget model. The ratio modeling approach was
      compared to a direct approach for concentration prediction, and also to a simple
      method where the mean ratio was used. The modeling performances of the ratio
      models were overall satisfying (r2 of 49% to 78%), and a better choice than the
      two other methods tested. This ratio modeling approach is based on a steady state
      assumption and largely ignores temporal dynamics. As such, this modeling
      technique does not replace the more physically-based techniques, but allows for
      hybrid approaches for improved spatial interpolations. This method could be used
      to predict effectively the impact (at equilibrium) of land use change and
      management scenarios on water quality at a regional scale.

PMID- 21962929
TI  - High pressure magnetic resonance imaging with metallic vessels.
AB  - High pressure measurements in most scientific fields rely on metal vessels given
      the superior tensile strength of metals. We introduce high pressure magnetic
      resonance imaging (MRI) measurements with metallic vessels. The developed MRI
      compatible metallic pressure vessel concept is very general in application.
      Macroscopic physical systems are now amenable to spatially resolved nuclear
      magnetic resonance (NMR) study at variable pressure and temperature. Metallic
      pressure vessels not only provide inherently high tensile strengths and efficient
      temperature control, they also permit optimization of the MRI RF probe
      sensitivity. An MRI compatible pressure vessel is demonstrated with a rock core
      holder fabricated using non-magnetic stainless steel. Water flooding through a
      porous rock under pressure is shown as an example of its applications. High
      pressure NMR spectroscopy plays an indispensable role in several science fields.
      This work will open new vistas of study for high pressure material science MRI
      and MR.

PMID- 21962930
TI  - Non-uniformly sampled Maximum Quantum spectroscopy.
AB  - Maximum-Quantum (MaxQ) NMR is an approach that exploits the simple lineshape (a
      singlet) of the highest possible coherence quantum order for a given spin system
      to help resolving the interpretation of the spectrum of complex mixtures. In this
      setup, resolution in the indirect, multiple-quantum, dimension is crucial, and it
      may be linked to a long duration of the signal acquired along this axis. We
      explored if this boundary on the length of the indirect dimension could not
      necessarily translate into extended experimental times by applying Non-Uniform
      Sampling (NUS) schemes in conjunction with Recursive Multi-Dimensional
      Decomposition (R-MDD) data processing. The actual value of the MaxQ order depends
      on the size of the spin system, so that for a mixture several MQ correlation
      spectra must be recorded to detect all possible molecular fragments. As the
      sparseness of the MQ datasets vary dramatically in going from higher (sparser) to
      lower (denser) coherence orders, the optimal compressing conditions and the
      fidelity of NUS/R-MDD scheme may vary along the series of MQ spectra. The NUS
      MaxQ approach is demonstrated on the aromatic region of the 1H spectrum of a
      mixture of 10 simple aromatic molecules.

PMID- 21962932
TI  - Effects of low-dose doxycycline on cytokine secretion in human monocytes
      stimulated with Aggregatibacter actinomycetemcomitans.
AB  - Doxycycline is an antibiotic used in the treatment of a variety of inflammatory
      conditions, including periodontitis. Apart from its antimicrobial properties,
      this drug also has independent anti-inflammatory effects at sub-antimicrobial
      doses. The present study aimed to investigate the effects of low-doses of
      doxycycline (LDD) on cytokine production by human monocytic cells challenged with
      the periodontal pathogen Aggregatibacter actinomycetemcomitans, for up to 6 h.
      The simultaneous regulation of 12 cytokines were measured by a Human Cytokine
      Array Kit. To validate the array findings, selected cytokines were also measured
      by enzyme-linked immunosorbant assay (ELISA). A. actinomycetemcomitans stimulated
      the production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1alpha, IL
      1beta, IL-6 and IL-8 by the cells after 6 h of challenge, and doxycycline
      significantly inhibited this effect. The kinetics of this regulation demonstrated
      an early (within 2 h) and significant (P<0.05) inhibition of pro-inflammatory
      cytokines, with a mild (0.5-fold) up-regulation of the anti-inflammatory cytokine
      IL-10. The results indicate that LDD acts as an anti-inflammatory agent in human
      monocytic cells stimulated with A. actinomycetemcomitans. This model provides
      clear evidence that some of the clinically proven benefits of LDD may be related
      to its ability to regulate inflammatory mediator release by monocytic cells. This
      property may contribute to the clinically proven benefits of this antibiotic as
      an adjunctive treatment for periodontitis.

PMID- 21962931
TI  - Artificial gravity with ergometric exercise preserves the cardiac, but not
      cerebrovascular, functions during 4 days of head-down bed rest.
AB  - Cardiovascular and musculoskeletal deconditioning occurring in long-term
      spaceflight requires new strategies to counteract these adverse effects. We
      previously reported that a short-arm centrifuge produced artificial gravity (AG),
      together with ergometer, has an approving effect on promoting cardiovascular
      function. The current study sought to investigate whether the cardiac and
      cerebrovascular functions were maintained and improved using a strategy of AG
      combined with exercise training on cardiovascular function during 4-day head-down
      bed rest (HDBR). Twelve healthy male subjects were assigned to a control group
      (CONT, n=6) and an AG combined with ergometric exercise training group (CM, n=6).
      Simultaneously, cardiac pumping and systolic functions, cerebral blood flow were
      measured before, during, and after HDBR. The results showed that AG combined with
      ergometric exercise caused an increase trend of number of tolerance, however,
      there was no significant difference between the two groups. After 4-day HDBR in
      the CONT group, heart rate increased significantly (59+/-6 vs 66+/-7 beats/min),
      while stroke volume (98+/-12 vs 68+/-13 mL) and cardiac output (6+/-1 vs 4+/-1
      L/min) decreased significantly (p<0.05). All subjects had similar drops on
      cerebral vascular function. Volume regulating hormone aldosterone increased in
      both groups (by 119.9% in CONT group and 112.8% in the CM group), but only in the
      CONT group there were a significant changes (p<0.05). Angiotensin II was
      significantly increased by 140.5% after 4-day HDBR in the CONT group (p<0.05),
      while no significant changes were observed in the CM group. These results
      indicated that artificial gravity with ergometric exercise successfully
      eliminated changes induced by simulated weightlessness in heart rate, volume
      regulating hormones, and cardiac pumping function and partially maintained
      cardiac systolic function. Hence, a daily 1h alternating +1.0 and +2.0 Gz with 40
      W exercise training appear to be an effective countermeasure against cardiac
      deconditioning.

PMID- 21962935
TI  - Evaluation of contact precautions discharges in an acute care setting.
AB  - The health care environment is increasingly discussed as a source of health care
      associated infections. We evaluated patterns of discharges among patients on
      contact precautions (CP) and assessed correlation of CP discharges with health
      care acquisition of organisms requiring CP and evaluated the feasibility of
      targeting CP discharges for additional monitoring.

PMID- 21962934
TI  - Evaluation of screening risk and nonrisk patients for methicillin-resistant
      Staphylococcus aureus on admission in an acute care hospital.
AB  - BACKGROUND: Screening for methicillin-resistant Staphylocccus aureus (MRSA) is
      advocated as part of control measures, but screening all patients on admission to
      hospital may not be cost-effective. OBJECTIVE: Our objective was to evaluate the
      additional yield of screening all patients on admission compared with only
      patients with risk factors and to assess cost aspects. METHODS: A prospective,
      nonrandomized observational study of screening nonrisk patients <=72 hours of
      admission compared with only screening patients with risk factors over 3 years in
      a tertiary referral hospital was conducted. We also assessed the costs of
      screening both groups. RESULTS: A total of 48 of 892 (5%) patients was MRSA
      positive; 28 of 314 (9%) during year 1, 12 of 257 (5%) during year 2, and 8 of
      321 (2%) during year 3. There were significantly fewer MRSA-positive patients
      among nonrisk compared with MRSA-risk patients: 4 of 340 (1%) versus 44 of 552
      (8%), P <= .0001, respectively. However, screening nonrisk patients increased the
      number of screening samples by 62% with a proportionate increase in the costs of
      screening. A backward stepwise logistic regression model identified age > 70
      years, diagnosis of chronic pulmonary disease, previous MRSA infection, and
      admission to hospital during the previous 18 months as the most important
      independent predictors to discriminate between MRSA-positive and MRSA-negative
      patients on admission (94.3% accuracy, P < .001). CONCLUSION: Screening patients
      without risk factors increased the number of screenings and costs but resulted in
      few additional cases being detected. In a hospital where MRSA is endemic,
      targeted screening of at-risk patients on admission remains the most efficient
      strategy for the early identification of MRSA-positive patients.

PMID- 21962936
TI  - Profiling health and health-related services for children with special health
      care needs with and without disabilities.
AB  - OBJECTIVE: The aims of this study were to profile and compare the health and
      health services characteristics for children with special health care needs
      (CSHCN), with and without disabilities, and to determine factors associated with
      unmet need. METHODS: Secondary data analysis of the 2005-2006 National Survey of
      Children with Special Health Care Needs was conducted. The sociodemographics,
      health, and health services of CSHCN with and without disabilities were compared.
      Multivariable logistic regression was employed to examine factors associated with
      unmet need for health services. RESULTS: Children from minority racial and ethnic
      groups and children living in or near poverty were over-represented among CSHCN
      with disabilities, compared with other CSHCN. Statistically higher percentages of
      CSHCN with disabilities had behavioral problems (39.6% vs 25.2%),
      anxiety/depressed mood (46.1% vs 24.0%), and trouble making/keeping friends
      (38.1% vs 15.6%) compared with other CSHCN. Thirty-two percent of CSHCN with
      disabilities received care in a medical home compared with 51% of other CSHCN.
      CSHCN with disabilities had higher rates of need and unmet need than other CSHCN
      for specialty care, therapy services, mental health services, home health,
      assistive devices, medical supplies, and durable medical equipment. The adjusted
      odds of unmet need for CSHCN with disabilities were 71% higher than for other
      CSHCN. CONCLUSION: CSHCN with disabilities had more severe health conditions and
      more health services need, but they less commonly received care within a medical
      home and had more unmet need. These health care inequities should be amenable to
      policy and health service delivery interventions to improve outcomes for CSHCN
      with disabilities.

PMID- 21962937
TI  - Comparison analysis between conventional ultrasonography and ultrasound
      elastography of thyroid nodules.
AB  - OBJECTIVE: To compare the effectiveness of conventional ultrasonography and
      ultrasound elastography in differential diagnosis of thyroid nodular diseases.
      METHODS: 244 patients with 291 thyroid nodules were examined by ultrasonography
      and ultrasound elastography respectively; the examination results were compared
      against pathological findings to determine the effectiveness of these two
      examination methods. RESULTS: The sensitivity and positive predictive value of
      conventional ultrasonography is higher than those of ultrasound elastography, but
      its specificity, accuracy, and negative predictive value is lower than those of
      the later. CONCLUSIONS: Ultrasound elastography is superior to conventional
      ultrasonography in differential diagnosis of thyroid nodules. However,
      ultrasonography is the basis of examination; only on this basis, an additional
      ultrasound elastography examination could greatly improve the diagnostic rate of
      thyroid nodular diseases.

PMID- 21962938
TI  - Successful reintroduction of valproic acid after the occurrence of pancytopenia.
AB  - BACKGROUND: Valproic acid is associated with a variety of hematologic
      abnormalities, most commonly thrombocytopenia. Pancytopenia is much less common
      and potentially much more serious. Little is known about the natural course of
      valproate-induced pancytopenia. CASE SUMMARY: We present a patient who developed
      pancytopenia while taking valproic acid for bipolar illness. After failing to
      respond to several other mood stabilizers, valproic acid was cautiously
      reintroduced with close hematologic monitoring. The pancytopenia has not recurred
      in the past 6 months. CONCLUSIONS: Pancytopenia may not represent an absolute
      contraindication to continuing valproate therapy, although caution is warranted.

PMID- 21962939
TI  - Monitoring a mixed starter of Hanseniaspora vineae-Saccharomyces cerevisiae in
      natural must: impact on 2-phenylethyl acetate production.
AB  - The effect of simultaneous or sequential inoculation of Hanseniaspora vineae CECT
      1471 and Saccharomyces cerevisiae T73 in non-sterile must on 2-phenylethyl
      acetate production has been examined. In both treatments tested, no significant
      differences in Saccharomyces yeast growth were found, whereas non-Saccharomyces
      yeast growth was significantly different during all days of fermentation.
      Independently of the type of inoculation, S. cerevisiae was the predominant
      species from day 3 till the end of the fermentation. The dynamics of indigenous
      and inoculated yeast populations showed H. vineae to be the predominant non
      Saccharomyces species at the beginning of fermentation in sequentially inoculated
      wines, whereas the simultaneous inoculation of S. cerevisiae did not permit any
      non-Saccharomyces species to become predominant. Differences found in non
      Saccharomyces yeast growth in both fermentations influenced the analytical
      profiles of final wines and specifically 2-phenylethyl acetate concentration
      which was two-fold increased in sequentially inoculated wines in comparison to
      those co-inoculated. In conclusion we have shown that H. vineae inoculated as
      part of a sequential mixed starter is able to compete with native yeasts present
      in non-sterile must and modify the wine aroma profile.

PMID- 21962940
TI  - Use of a multivariate approach to assess the incidence of Alicyclobacillus spp.
      in concentrate fruit juices marketed in Argentina: results of a 14-year survey.
AB  - The purpose of this study was to determine the incidence of Alicyclobacillus spp.
      in fruit/vegetable juices (concentrated pulps and clarified and non-clarified
      juices) marketed in Argentina between 1996 and 2009. The presence of
      Alicyclobacillus was determined in a total of 8556 samples of fruit and vegetable
      juices (apple, pear, grape, peach, blend of juices, tangerine, pineapple, orange,
      mango, plum, guava, apricot, lemon, banana, kiwi, carrot, strawberry, grapefruit,
      and beetroot) collected in seven Argentinean provinces. Multiple factor analysis
      (MFA) was carried out on a data matrix that contained the percentage of positive
      samples, type of juice, raw material and production year. Except for kiwi and
      orange, Alicyclobacillus was found in juices from all the evaluated raw
      materials. The highest percentage of positive samples was found for beetroot,
      strawberry, banana, peach, mango, carrot and plum juices. The percentage of
      positive samples for these juices ranged from 100% to 24%. Furthermore, the
      application of multivariate techniques provided an insight on the relationship
      between the incidence of Alicyclobacillus and production variables. This approach
      enabled the identification of the most relevant variables that increased the
      percentage of positive samples among the juices, which could help in developing
      strategies to avoid the incidence of this bacterium. By means of hierarchical
      cluster analysis seven groups (clusters) of juices which showed different
      percentages of positive samples for Alicyclobacillus spp. were identified. This
      analysis showed that pineapple, peach, strawberry, mango and beetroot juices had
      higher rates of positivity for Alicyclobacillus than the rest of the evaluated
      juices. MFA analysis also showed that some clear relationships could be
      highlighted between the percentage of samples positive for Alicyclobacillus and
      five types of fruit juices (strawberry, beetroot, grapefruit, pineapple and
      mango). It was observed that a large proportion of juices produced in 2000, 2005
      and 2008 were located in clusters with higher incidence of Alicyclobacillus spp.,
      whereas a larger proportion of clarified concentrate juice and concentrate pulp
      samples showed higher probability of incidence of Alicyclobacillus in these
      products. Data presented in this study brings a contribution to the ecology of
      Alicyclobacillus in fruit/vegetable juices marketed in Argentina. This
      information would be useful to enhance the microbiological stability of fruit
      juices regarding the presence of Alicyclobacillus spp.

PMID- 21962941
TI  - Normalization of basal metabolic rate for differences in body weight in pregnant
      women.

PMID- 21962942
TI  - Association of glutathione S-transferase M1 and T1 null polymorphisms with the
      development of cervical lesions: a meta-analysis.
AB  - OBJECTIVES: An accumulation of evidence suggests that gene-based self
      susceptibility may contribute to the development of cancer. Some studies have
      found that particular polymorphisms of the glutathione S-transferase M1 and T1
      genes are associated with increased risk of cervical lesions, but other studies
      have had contrary results. The present meta-analysis evaluated the association of
      glutathione S-transferase M1 and T1 null polymorphisms with the development of
      cervical lesions. In addition, stratified analyses were performed in an attempt
      to identify any race-specific effects. STUDY DESIGN: Twenty-one related studies
      were included in the meta-analysis, comprising glutathione S-transferase M1 data
      from 1423 patients with cervical lesions and 2415 healthy matched controls, and
      glutathione S-transferase T1 data from 2081 patients with cervical lesions and
      2287 healthy matched controls. The fixed-effect model (Mantel-Haenszel method)
      and the random-effect (DerSimonian and Laird) model were used to examine the
      difference in frequency of glutathione S-transferase M1 and T1 null polymorphisms
      between pre- and invasive cervical lesions. Subgroup analyses were also conducted
      to evaluate any race-specific effect on the frequencies of glutathione S
      transferase polymorphisms in cervical lesions. Odds ratios (OR) and 95%
      confidence intervals (CI) were calculated. Heterogeneity was assessed using the
      heterogeneity metric (I2) and Chi-squared test. RESULTS: The glutathione S
      transferase M1 null polymorphism was associated with increased risk of low-grade
      intra-epithelial lesions (OR 1.37, 95% CI 1.05-1.77), but no increased risk of
      high-grade intra-epithelial lesions (OR 1.29, 95% CI 0.87-1.8) or invasive
      cervical cancer (OR 1.20, 95% CI 0.99-1.46). The association seemed to be
      confined to Southeast Asians (OR 1.97, 95% CI 1.44-2.71). No significant
      associations were found for the glutathione S-transferase T1 null polymorphism
      for any of the populations. CONCLUSIONS: The glutathione S-transferase M1 null
      polymorphism significantly increases susceptibility to early-stage cervical
      lesions in Southeast Asians. However, the glutathione S-transferase T1 null
      polymorphism does not appear to be a risk factor for cervical lesions in any
      population.

PMID- 21962943
TI  - Combination of misoprostol and mechanical dilation for induction of labour: a
      randomized controlled trial.
AB  - OBJECTIVE: To evaluate a combination of oral misoprostol (OM) and mechanical
      dilation of the cervix to improve efficacy in inducing labour. STUDY DESIGN: This
      prospective, randomized study included 122 term pregnancies with an indication
      for induced labour. Each woman was randomly assigned to one of two groups. In the
      study group, a combination of OM and mechanical dilation with a double-balloon
      catheter for cervical ripening was used. In the control group, only OM was
      administered. The primary outcome measure was the rate of failure to induce
      labour, defined as no vaginal delivery within 48h. RESULTS: In the study group,
      the rate of failure to induce labour was significantly lower in comparison with
      the control group (9.3% vs. 21.2%; P=0.007). The median times for inducing labour
      were 15.3h in the study group and 20.8h in the control group (P=0.158). There
      were no significant differences between the two groups with regard to other
      outcome parameters. As there were no failures of induced labour among women with
      premature rupture of membranes, the study results were also evaluated after
      excluding these cases. Among those women without rupture of membranes, the median
      times for induction were 15.8h in the study group and 32.6h in the control group
      (P=0.024). The rates of failure to induce labour were 10.8% vs. 28.2% (P=0.002).
      CONCLUSION: A combination of OM and a double-balloon catheter improves the
      efficacy of labour induction in term pregnancies, particularly in women without
      premature rupture of the membranes.

PMID- 21962944
TI  - Immature teratoma of the greater omentum.

PMID- 21962946
TI  - The influence of physical properties and morphology of crystallised lactose on
      delivery of salbutamol sulphate from dry powder inhalers.
AB  - The aim of this work was to investigate the mechanistic evaluation of
      physicochemical properties of new engineered lactose on aerosolisation
      performance of salbutamol sulphate (SS) delivered from dry powder inhaler (DPI).
      Different crystallised lactose particles were obtained from binary mixtures of
      butanol:acetone. The sieved fractions (63-90 MUm) of crystallised lactose were
      characterised in terms of size, shape, flowability, true density and
      aerosolisation performance (using multiple twin stage impinger (MSLI),
      Aerolizer((r)) inhaler device, and salbutamol sulphate as a model drug). Compared
      to commercial lactose, crystallised lactose particles were less elongated,
      covered with fine lactose particles, and had a rougher surface morphology. The
      crystallised lactose powders had a considerably lower bulk and tap density and
      poorer flow when compared to commercial lactose. Engineered carrier with better
      flow showed improved drug content homogeneity, reduced amounts of drug
      "deposited" on the inhaler device and throat, and a smaller drug aerodynamic
      diameter upon inhalation. Aerodynamic diameter of salbutamol sulphate increased
      as lactose aerodynamic diameter decreased (linear, R(2)=0.9191) and/or as fine
      particle lactose content increased (linear, R(2)=0.8653). Improved drug
      aerosolisation performance in the case of crystallised lactose particles was
      attributed to lower drug-carrier adhesion forces due to a rougher surface and
      higher fine particle content. In conclusion, this work proved that using binary
      combinations of solvents in crystallisation medium is vital in modification of
      the physicochemical and micromeritic properties of carriers to achieve a
      desirable aerosolisation performance from DPI formulations. Among all lactose
      samples, lactose particles crystallised from pure butanol generated the highest
      overall DPI formulations desirability.

PMID- 21962945
TI  - Difficulty processing temporary syntactic ambiguities in Lewy body spectrum
      disorder.
AB  - While grammatical aspects of language are preserved, executive deficits are
      prominent in Lewy body spectrum disorder (LBSD), including Parkinson's disease
      (PD), Parkinson's dementia (PDD) and dementia with Lewy bodies (DLB). We examined
      executive control during sentence processing in LBSD by assessing temporary
      structural ambiguities. Using an on-line word detection procedure, patients heard
      sentences with a syntactic structure that has high-compatibility or low
      compatibility with the main verb's statistically preferred syntactic structure,
      and half of the sentences were lengthened strategically between the onset of the
      ambiguity and its resolution. We found selectively slowed processing of
      lengthened ambiguous sentences in the PDD/DLB subgroup. This correlated with
      impairments on measures of executive control. Regression analyses related the
      working memory deficit during ambiguous sentence processing to significant
      cortical thinning in frontal and parietal regions. These findings emphasize the
      role of prefrontal disease in the executive limitations that interfere with
      processing ambiguous sentences in LBSD.

PMID- 21962947
TI  - In vitro morphogenesis of PANC-1 cells into islet-like aggregates using RGD
      covered dextran derivative surfaces.
AB  - Substrates bearing low-fouling carboxymethyl dextran (CMD) upon which RGD is
      covalently grafted were validated to study PANC-1 cell differentiation in serum
      free medium. When exposed to RGD-CMD, cells lightly adhered to the surface and
      formed islet-like aggregates (ILAs) in contact with the surface. PANC-1 were non
      adherent on RGE-CMD, CMD, and tissue culture polystyrene surfaces and aggregated
      in suspension forming ILAs. RGD-CMD resulted in smaller ILAs. Ki67 and CK-19
      expression decreased after 3, 7, and 14 days. E-cadherin expression did not
      change from 3 to 7 days, but decreased after 14 days. For each marker, there was
      no difference in the expression between the surfaces. After 14 days, ILAs weakly
      expressed insulin and glucagon and the expression level was independent of the
      surfaces. No convincing level of insulin or glucagon was detected by
      immunostaining at 3 and 7 days. A higher level of insulin release was detected in
      the media after 14 days for cells grown on RGD-CMD. After 14 days, there were
      three-fold more cells on RGD-CMD surfaces compared to cell numbers found in other
      culture conditions. alpha(5) integrin expression was rampant throughout ILAs for
      all four surfaces. alpha(V)beta(3) integrin expression was only noticeable for
      ILAs cultured on RGD-CMD surfaces.

PMID- 21962948
TI  - Retrieval of a penny from the pediatric esophagus: a cost analysis.
AB  - OBJECTIVE: As part of the oral phase of development, children commonly ingest
      foreign bodies. The most common lodged foreign body, requiring operative removal,
      in the United States is the penny. Valued at 1 cent, comprised of materials
      valued at less than 1 cent, costing 1.62 cents to manufacture, and being never
      removed from circulation, pennies are aplenty. But ingestion can lead to mucosal
      damage, the consequences of which can be esophageal perforation or stricture
      formation. We hypothesize that the monetary value of the penny is far less than
      the cost of its ingestion and removal. This quality assurance study examines the
      effect of the penny on the purse. PATIENTS AND METHODS: This retrospective review
      identified 180 foreign bodies in children under the age of 18 over a five year
      period. Eighty-two were pennies. Operative notes revealed degree of injury.
      Hospital charge assessments revealed the "cost" of each visit. RESULTS: There
      were no esophageal perforations, and cases were divided evenly among injury
      grades 0-III. The average total charge for all penny-related injuries was
      $7164.78. CONCLUSIONS: The purpose was to examine the actual cost of a penny
      (more than its value in production) and the potential cost of its damage
      (thousands of dollars in measurable costs, untold immeasurable costs). The goal
      of this study is to draw healthcare professional and public attention to a
      potentially serious and yet highly preventable injury in young children.

PMID- 21962949
TI  - Low frequency of GJB2 mutations in thirty-five students with hearing loss in
      Chinese consanguineous families.
AB  - OBJECTIVE: GJB2 mutation is recognized as the prevalent causes of non-syndromic
      hearing impairment (NSHI) worldwide. However, the mutation profiles of this gene
      are unknown in deafness probands in the consanguineous pedigrees in China.
      Therefore, this study aimed to characterize the forms and frequencies of GJB2
      mutations in 35 students with hearing loss in the consanguineous families in
      Hubei province, Central China. METHODS: Genomic DNA was extracted from blood
      samples of 35 students with hearing loss. The target fragments were amplified by
      polymerase chain reaction (PCR) and subjected to sequencing to identify sequence
      variations. RESULTS: Surprisingly, none of these probands harbored homozygous
      mutation in GJB2. Three GJB2 heterozygous mutations were identified: a single
      base pair substitution c.35G>T and c.139G>T, and a 2 bp deletion c.299-300delAT
      in three probands. CONCLUSION: The frequency of GJB2 mutation is relatively low
      in these consanguineous families, most of which were minorities. Our results
      suggest that screening for responsible genes other than GJB2 may be necessary for
      NSHI in these minorities.

PMID- 21962950
TI  - Add-on lacosamide: a retrospective study on the relationship between serum
      concentration, dosage, and adverse events.
AB  - We performed a retrospective study in patients with poorly controlled epilepsy
      treated with add-on lacosamide (LCM) to investigate the relationship of LCM
      related adverse events with LCM serum concentration and weight-dependent dosage.
      We collected serum concentrations, weight-related dosages, and occurrences of the
      seven most frequent adverse events according to the randomized double-blind,
      placebo-controlled trials. Seventy of 131 patients could be sufficiently
      evaluated. LCM serum concentrations and weight-related dosages in patients with
      and without typical adverse events did not differ significantly. Closer analysis
      of the data suggested that dizziness as the leading adverse event occurred
      significantly more often if LCM was combined with classic sodium channel
      blockers. There was a significant correlation between LCM serum concentrations
      and co-medication, so there is still evidence for dependent variables that might
      have a relevant impact in individual cases. However, our data do not allow
      definition of a safety range for LCM.

PMID- 21962951
TI  - Caregiver measures for seizure control, efficacy, and tolerability of
      antiepileptic drugs for childhood epilepsy: results of a preference survey.
AB  - We sought to identify and quantify caregiver-defined characteristics of efficacy
      related to the perceived success of antiepileptic drug (AED) use. A 22-question
      survey was designed using physician input, focus groups, and clinical trial
      endpoints. Responses were pooled and analyzed with regard to seizure type and
      treatment, categorized as controlled (exposure to 1 AED), adjunctive (exposure to
      2 AEDs), or refractory (exposure to >=3 AEDs). Two hundred ninety-five surveys
      were completed: 109 (37%) controlled, 84 (28%) adjunctive, and 102 (35%)
      refractory. Seizure freedom and median seizure reduction >90% maintained for >1
      year were reported as the most important indicators of medication efficacy by the
      majority of respondents. These measures were the same regardless of seizure type
      or treatment category. Our results demonstrate that current trial design may be
      inadequate to address the expectations of patients. Incorporating patient-defined
      AED efficacy measures may improve satisfaction and informed decision making
      regarding epilepsy treatment.

PMID- 21962952
TI  - Outpatient surgery for vesicoureteral reflux: endoscopic injection vs
      extravesical ureteral reimplantation.

PMID- 21962954
TI  - Metabolic syndrome, diabetes, and coronary artery disease: a very common
      association.

PMID- 21962953
TI  - [The heart during pregnancy].
AB  - During pregnancy, there are a number of important changes to cardiovascular
      function which are necessary for progression of a successful pregnancy.
      Additionally, preexisting cardiovascular conditions can be exacerbated by the
      adaptations that occur during gestation. These can present serious therapeutic
      challenges in the management of the cardiology patient during pregnancy.
      Significantly, the number of pregnant women at risk of cardiovascular
      complications is on the rise, so identification of risk factors that predict
      cardiac outcomes is essential to proper screening of the obstetrical patient. In
      diagnosed preexisting conditions, such as pulmonary hypertension, counseling is
      important prior to pregnancy. In the case of underlying disorders unmasked by
      pregnancy, or new-onset complications like preeclampsia, appropriate monitoring
      and treatment of the cardiovascular complications is warranted. Ultimately,
      collaborative care by both obstetricians and cardiologists is essential for the
      successful resolution of cardiovascular dysfunction in the obstetrical patient.

PMID- 21962955
TI  - [Spanish cardiac catheterization and coronary intervention registry. 20th
      official report of the spanish society of cardiology working group on cardiac
      catheterization and interventional cardiology (1990-2010)].
AB  - INTRODUCTION AND OBJECTIVES: The Working Group on Cardiac Catheterization and
      Interventional Cardiology presents on a yearly basis a report on the data
      collected for the national registry. This information displays how procedures are
      distributed throughout Spain and makes comparisons with other countries feasible.
      METHODS: Institutions render their data voluntarily (online) and they are
      analyzed by the Working Group's steering committee. RESULTS: Data was sent by 113
      hospitals (71 public and 41 private) that treat mainly adults, reporting 135 486
      diagnostic procedures, 119 118 of them coronary angiograms, slightly less than
      the year before, and with a rate of 2945 coronary angiograms per million
      inhabitants. Percutaneous coronary interventions increased a bit, to 64331
      procedures and a rate of 1398 interventions per million. Of 100371 stents
      implanted, 61.3% were drug-eluting stents. In the acute phase of myocardial
      infarction, 14248 coronary interventions were carried out, 6% more than in 2009
      and 22% of the total number of coronary interventions. The most frequent
      intervention for adult congenital heart disease was closure of an atrial septal
      defect (295 procedures). Percutaneous mitral valvuloplasty continues to decrease
      (326 procedures) and percutaneous aortic valve implantations are growing rapidly,
      with 655 units implanted in 2010. CONCLUSIONS: The greatest increase in activity
      has occurred in the field of myocardial infarction and percutaneous aortic valve
      implantation. The other procedures, both diagnostic and therapeutic, remain
      stable.

PMID- 21962956
TI  - [1980-2010: the three glorious decades of cardiology. A comprehensive and
      collective effort rewarded by outstanding clinical results].

PMID- 21962959
TI  - Conscious perception and the frontal lobes: comment on Lau and Rosenthal.

PMID- 21962958
TI  - [Analyzing the coronary heart disease mortality decline in a Mediterranean
      population: Spain 1988-2005].
AB  - INTRODUCTION AND OBJECTIVES: To examine the extent to which the decrease in
      coronary heart disease mortality rates in Spain between 1988 and 2005 could be
      explained by changes in cardiovascular risk factors and by the use of medical and
      surgical treatments. METHODS: We used the previously validated IMPACT model to
      examine the contributions of exposure factors (risk factors and treatments) to
      the main outcome, changes in the mortality rates of death from coronary heart
      disease, among adults 35 to 74 years of age. Main data sources included official
      mortality statistics, results of longitudinal studies, national surveys,
      randomized controlled trials, and meta-analyses. The difference between observed
      and expected coronary heart disease deaths in 2005 was then partitioned between
      treatments and risk factors. RESULTS: From 1988 to 2005, the age-adjusted
      coronary heart disease mortality rates fell by almost 40%, resulting in 8530
      fewer coronary heart disease deaths in 2005. Approximately 47% of the fall in
      deaths was attributed to treatments. The major treatment contributions came from
      initial therapy for acute coronary syndromes (11%), secondary prevention (10%),
      and heart failure (9%). About 50% of the fall in mortality was attributed to
      changes in risk factors. The largest mortality benefit came from changes in total
      cholesterol (about 31% of the mortality fall) and in systolic blood pressure
      (about 15%). However, some substantial gender differences were observed in risk
      factor trends with an increase in diabetes and obesity in men and an increase in
      smoking in young women. These generated additional deaths. CONCLUSIONS:
      Approximately half of the coronary heart disease mortality fall in Spain was
      attributable to reductions in major risk factors, and half to evidence-based
      therapies. These results increase understanding of past trends and will help to
      inform planning for future prevention and treatment strategies in low-risk
      populations.

PMID- 21962960
TI  - Pharmacological stimulation of sperm motility in frozen and thawed testicular
      sperm using the dimethylxanthine theophylline.
AB  - OBJECTIVE: To evaluate whether the use of theophylline improves sperm motility
      and treatment outcome in frozen-thawed testicular sperm extraction (TESE).
      DESIGN: Artificial sperm activation was offered to azoospermic patients between
      January and October 2010 in two different centers (identical lab conditions).
      SETTING: IVF units of public hospitals. PATIENT(S): Sixty-five patients
      participated and gave informed consent. INTERVENTION(S): Sibling oocytes were
      split into a study (intracytoplasmic sperm injection [ICSI] with thawed
      testicular sperm treated with theophylline) and a control group (ICSI with thawed
      untreated sperm). MAIN OUTCOME MEASURE(S): Sperm motility, time for sperm
      selection, rates of fertilization, implantation, clinical pregnancy, and live
      birth. RESULT(S): All patients but one (98.5%) showed a significant improvement
      in testicular sperm motility when theophylline was used. In addition, sperm
      selection took significantly less time in the study as compared with in the
      untreated control group. Corresponding rates of fertilization (79.9% vs. 63.3%)
      and blastulation (63.9% vs. 46.8%) were significantly increased. Significantly
      more patients achieved clinical pregnancy if embryos/blastocysts derived from
      oocytes that had been injected with pharmacologically stimulated testicular
      spermatozoa were transferred (53.9% vs. 23.8%). This also holds true for the
      implantation rate. CONCLUSION(S): Theophylline turned out to be a reliable tool
      in stimulating testicular spermatozoa after thawing. Its immediate effect allows
      for faster and more accurate selection of viable sperm, which in turn improved
      fertilization and pregnancy outcome in this prospective study.

PMID- 21962961
TI  - Identification of a novel mutation in exon 1 of androgen receptor gene in an
      azoospermic patient with mild androgen insensitivity syndrome: case report and
      literature review.
AB  - OBJECTIVE: To report a case of an azoospermic subject with mild androgen
      insensitivity syndrome (MAIS) and review the relevant literature. DESIGN: Case
      report. SETTING: Academic research hospital. PATIENT(S): A 49-year-old man with
      undermasculinized features and a history of cryptorchidism and azoospermia.
      INTERVENTION(S): Hormonal evaluation and genetic testing of the androgen receptor
      gene (AR). MAIN OUTCOME MEASURE(S): Hormonal levels and sequence chromatogram of
      the proband and his mother. RESULT(S): We found total T in the normal range and
      high levels of gonadotropins. Karyotype was 46,XY. Genetic testing identified a
      novel mutation of exon 1 of AR, which resulted in an alanine to serine
      substitution in the transactivation domain at codon 240 (A240S). Fourteen other
      mutations of exon 1 of AR have been associated with MAIS to date. CONCLUSION(S):
      The novel mutation A240S of AR is involved in MAIS, a syndrome associated with
      azoospermia.

PMID- 21962962
TI  - Magnetic resonance imaging visualization of a vaginal septum.
AB  - Magnetic resonance imaging is considered the gold-standard imaging technique in
      cases of Mullerian and vaginal anomalies, however, vaginal delineation often
      proves difficult, owing to the fact that vaginal walls are normally collapsed and
      in close proximity. Instilling gel through the introitus allows for better
      depiction of the distal vagina.

PMID- 21962963
TI  - Randomized comparison of the influence of dietary management and/or physical
      exercise on ovarian function and metabolic parameters in overweight women with
      polycystic ovary syndrome.
AB  - OBJECTIVE: To compare the influence of dietary management and/or physical
      exercise on ovarian function and metabolic variables in women with polycystic
      ovary syndrome (PCOS). DESIGN: Randomized 4-month trial with three interventions
      and a long-term follow-up. SETTING: Women's health clinical research unit at a
      university hospital. PATIENT(S): Fifty-seven overweight/obese women with PCOS.
      INTERVENTION(S): Dietary management, physical exercise, or both, using programs
      individually adapted and supervised by a dietician and/or a physical therapist.
      MAIN OUTCOME MEASURE(S): Ovarian function, endocrinologic, and metabolic status
      and body composition. RESULT(S): On average, body mass index was reduced 6% by
      the dietary management, 3% by the exercise, and 5% by the combined interventions.
      Lower body fat and lean body mass were significantly decreased in the dietary
      groups, whereas upper body fat was lowered and lean body mass maintained by
      exercise alone. The menstrual pattern was significantly improved in 69% and
      ovulation confirmed in 34% of the patients, with no differences among the groups.
      The strongest predictor of resumed ovulation was a high serum level of insulin
      like growth factor-binding protein 1 after the intervention. Follow-up of one
      half of the patients for a median of 2.8 years revealed sustained weight
      reduction and improvement in menstrual pattern. CONCLUSION(S): Dietary management
      and exercise, alone or in combination, are equally effective in improving
      reproductive function in overweight/obese women with PCOS. The underlying
      mechanisms appear to involve enhanced insulin sensitivity. Supportive
      individualized programs for lifestyle change could exert long-term beneficial
      effects.

PMID- 21962964
TI  - Five-years of a mandatory single-embryo transfer (mSET) policy dramatically
      reduces twinning rate without lowering pregnancy rates.
AB  - OBJECTIVE: To report the outcomes of a program policy instituted in 2004
      mandating single-embryo transfer (mSET) for all women aged <38 years, with at
      least seven zygotes, no prior failed fresh cycle at our center, and at least one
      good-quality blastocyst. DESIGN: Retrospective cohort study. SETTING: Academic
      medical center. PATIENT(S): All women <38 years old undergoing a fresh cycle with
      autologous oocytes and all women undergoing a fresh cycle with donor oocytes from
      June 1, 1999, to May 31, 2004 (before mSET) and from June 1, 2004, to May 31,
      2009 (after mSET). INTERVENTION(S): mSET policy implementation. MAIN OUTCOME
      MEASURE(S): Live-birth rate, multiple pregnancy rate, clinical volume, and
      outcomes of all mSET fresh IVF transfers were analyzed. RESULT(S): Clinical
      volume was unchanged between the two time groups. After implementation of mSET,
      live-birth rates improved from 51.1% to 55.9% and multiple-birth rates dropped
      from 34.8% to 17.5%. A total of 364 mSET fresh transfers were performed with a
      live-birth rate of 64.6% and a multiple-birth rate of 3.4%. CONCLUSION(S): A
      mandatory SET policy based on prognostic factors can be instituted with no drop
      in clinical volume and no negative effect on delivery rates. Multiple gestation
      rates can be dramatically lowered.

PMID- 21962965
TI  - Toxoplasma gondii infection in sentinel and free-range chickens from Argentina.
AB  - This study aimed at isolating and genotyping Toxoplasma gondii from serologically
      positive free-range chickens from Argentina, and to evaluate the use of sentinel
      animals during a short time period of exposure to determine environmental
      contamination with T. gondii oocysts. Two groups of chickens on six farms were
      compared in this study: (i) young, 2-3 month-old broiler-type chickens reared as
      sentinel animals on the farms and (ii) adult chickens reared on the same farms
      for more than one year. Seroconversion rates of 7.0% or 5.7% were observed in
      sentinel broiler chickens reared for a period of 74 days (January-April 2010) or
      88 days (August-November 2010) respectively, as shown by a T. gondii specific
      immunofluorescent antibody test. Fifty-three percent (17 of 32) of adult chickens
      were positive and showed higher titres than sentinel animals. Isolation of T.
      gondii from tissues (brain and heart) of serologically positive chickens was
      achieved from six of seven free-range adult birds with IFAT titres of 200 and
      higher. The isolated parasites were analysed by multi-locus polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP). The isolated T.
      gondii showed three different genotypes: two genotypes consisted in atypical
      allele combinations, and the remaining genotype had exclusively clonal type II
      alleles. All isolates obtained at a single farm, corresponded to the same
      genotype. The T. gondii genotypes observed are identical to those described in
      cats, dogs, chickens and capybaras elsewhere in South America. Two isolates,
      which showed different allele combinations in PCR-RFLP, were characterized in a
      mouse virulence assay. While one isolate showed a low virulence a second isolate
      was of intermediate virulence to mice.

PMID- 21962966
TI  - Strongylus vulgaris (Looss, 1900) in horses in Italy: is it still a problem?
AB  - A post-mortem survey was carried out on 46 Sardinian horses to evaluate the
      presence of Strongylus vulgaris and associated pathology. Horses were from local
      farms and had been treated with broad-spectrum anthelmintics at least 3 times a
      year. Examination of the cranial mesenteric arterial system (CMAS) showed
      parasite-induced lesions in all horses. S. vulgaris larvae were found in 39% of
      examined arteries, while their detection rate in coprocultures was 4%. Histology,
      carried out on 26 horses, showed mainly chronic and chronic-active lesions.
      Histometry showed a significant increase in thickness of the arterial wall, in
      particular of the intima tunic and adventitia tunic of the ileocolic artery and
      its colic branch. MCV, MCHC and alpha2, beta and gamma globulins were increased
      in horses with S. vulgaris larvae in the arteries, while the albumin/globulin
      ratio was decreased. Horses that were positive on faecal examination showed
      decreased values for RBC, PCV and the albumin/globulin ratio. Although several
      studies have shown a dramatic decrease of S. vulgaris infection worldwide, our
      data show that this parasite continues to exert its pathogenic role, even when
      its detection rate is quite low within the strongyle population infecting horses.

PMID- 21962967
TI  - Use of mixed cultures of biocontrol agents to control sheep nematodes.
AB  - Biological control is a promising non-chemical approach for the control of
      gastrointestinal nematodes of sheep. Use of combinations of biocontrol agents
      have been reported to be an effective method to increase the efficacy of
      biological control effects. In this study, combinations of either two Bacillus
      thuringiensis (Bt) or Clonostachys rosea (C. rosea) isolates and Bt+C. rosea
      isolates were evaluated in vitro in microtitre plates for their biocontrol
      activity on sheep nematodes. The Baermann technique was used to extract the
      surviving L3 larval stages of intestinal nematodes and counted under a dissecting
      microscope to determine the larval counts. Results indicate that there was a
      significant reduction of nematode counts due to combination of biocontrol agents
      (P<0.001). Combinations of Bt isolates reduced nematodes counts by 72.8%, 64% and
      29.8%. The results revealed a control level of 57% when C. rosea isolates P3+P8
      were combined. Combination of Bt and C. rosea isolates B10+P8 caused the greatest
      mortality of 76.7%. Most combinations were antagonistic, with only a few
      combinations showing an additive effect. None were synergistic. The isolate
      combinations were more effective than when isolates were used alone.

PMID- 21962968
TI  - Frequency distributions of helminths of wolves in Kazakhstan.
AB  - Between 2001 and 2008 a total of 41 wolves (Canis lupus) were necropsied in
      southern Kazakhstan and their intestinal parasite fauna evaluated. Of these
      animals 8 (19.5%) were infected with Echinococcus granulosus, 15 (36%) with
      Taenia spp, 13 (31.7%) with Dypilidium caninum, 5 (12.2%) with Mesocestoides
      lineatus, 15 (36.6%) with Toxocara canis, 16 (39%) with Toxascaris leonina, 8
      (19.5%) with Trichuris vulpis, 9 (22%) with Macracanthorhynchus catulinus and 1
      (2.4%) with Moniliformis moniliformis. All parasites had an aggregated
      distribution which followed a zero inflated or hurdle model. Although a small
      convenience sample of wolves, the results indicate a high prevalence of infection
      with E. granulosus. The mean abundance (1275 E. granulosus per wolf) was high
      with individual infected wolves carrying intensities of several thousand
      parasites. As wolves are common in Kazakhstan they may act as an important host
      in the transmission of this zoonotic parasite. The wolves were sampled from an
      area of Kazakhstan where there is a high prevalence of hydatid cysts in livestock
      and where echinococcosis has been observed in wild ungulates.

PMID- 21962969
TI  - Pyrosequencing analysis of the beta-tubulin gene in Spanish Teladorsagia
      circumcincta field isolates.
AB  - Benzimidazole (BZ) resistance in gastrointestinal nematodes has been associated
      with single nucleotide polymorphisms (SNPs) at codons 200, 167 and 198 in the
      beta-tubulin isotype 1 gene and, recently, these SNPs have also been found in
      macrocyclic lactone (ML) resistant strains of Haemonchus contortus. On this
      basis, we have studied the same putative SNPs in Spanish Teladorsagia
      circumcincta field isolates by pyrosequencing. Single L3 (infective 3rd stage
      larvae) from five sheep flocks were tested after confirming their BZ
      susceptibility and degree of ivermectin (IVM) resistance. According to the Faecal
      Egg Count Reduction Test (FECRT) one flock was classified as IVM susceptible,
      another one was resistant, and the rest had a suspicion of resistance to IVM. DNA
      extraction was carried out on 598 single L3 and 56% of these were identified as
      T. circumcincta after the amplification of a species-specific ITS2 fragment. The
      number of L3 analyzed for the SNPs 198/200 was 255 and for the SNP 167 was 187.
      Results clearly indicate no resistance-associated SNPs were present at any codon,
      before or after treatment. Therefore, all T. cicumcincta L3 were designated as
      susceptible homozygous genotypes for all SNPs. The absence of the mutations in
      these populations would argue against resistance haplotypes being present in the
      parasite population prior to drug treatment, at least in Spanish T. circumcincta.

PMID- 21962970
TI  - Are all sex chromosomes created equal?
AB  - Three principal types of chromosomal sex determination are found in nature: male
      heterogamety (XY systems, as in mammals), female heterogamety (ZW systems, as in
      birds), and haploid phase determination (UV systems, as in some algae and
      bryophytes). Although these systems share many common features, there are
      important biological differences between them that have broad evolutionary and
      genomic implications. Here we combine theoretical predictions with empirical
      observations to discuss how differences in selection, genetic properties and
      transmission uniquely shape each system. We elucidate how the differences among
      these systems can be exploited to gain insights about general evolutionary
      processes, genome structure, and gene expression. We suggest directions for
      research that will greatly increase our general understanding of the forces
      driving sex-chromosome evolution in diverse organisms.

PMID- 21962971
TI  - About PAR: the distinct evolutionary dynamics of the pseudoautosomal region.
AB  - Sex chromosomes differ from other chromosomes in the striking divergence they
      often show in size, structure, and gene content. Not only do they possess genes
      controlling sex determination that are restricted to either the X or Y (or Z or
      W) chromosomes, but in many taxa they also include recombining regions. In these
      'pseudoautosomal regions' (PARs), sequence homology is maintained by meiotic
      pairing and exchange in the heterogametic sex. PARs are unique genomic regions,
      exhibiting some features of autosomes, but they are also influenced by their
      partial sex linkage. Here we review the distribution and structure of PARs among
      animals and plants, the theoretical predictions concerning their evolutionary
      dynamics, the reasons for their persistence, and the diversity and content of
      genes that reside within them. It is now clear that the evolution of the PAR
      differs in important ways from that of genes in either the non-recombining
      regions of sex chromosomes or the autosomes.

PMID- 21962972
TI  - Multiple developmental processes underlie sex differentiation in angiosperms.
AB  - The production of unisexual flowers has evolved numerous times in dioecious and
      monoecious plant taxa. Based on repeated evolutionary origins, a great variety of
      developmental and genetic mechanisms underlying unisexual flower development is
      predicted. Here, we comprehensively review the modes of development of unisexual
      flowers, test potential correlations with sexual system, and end with a synthesis
      of the genetics and hormonal regulation of plant sex determination. We find that
      the stage of organ abortion in male and female flowers is temporally correlated
      within species and also confirm that the arrest of development does not tend to
      occur preferentially at a particular stage, or via a common process.

PMID- 21962973
TI  - Cell polarity in plants: when two do the same, it is not the same....
AB  - In unicellular and multicellular organisms, cell polarity is essential for a wide
      range of biological processes. An important feature of cell polarity is the
      asymmetric distribution of proteins in or at the plasma membrane. In plants such
      polar localized proteins play various specific roles ranging from organizing cell
      morphogenesis, asymmetric cell division, pathogen defense, nutrient transport and
      establishment of hormone gradients for developmental patterning. Moreover,
      flexible respecification of cell polarities enables plants to adjust their
      physiology and development to environmental changes. Having evolved
      multicellularity independently and lacking major cell polarity mechanisms of
      animal cells, plants came up with alternative solutions to generate and respecify
      cell polarity as well as to regulate polar domains at the plasma membrane.

PMID- 21962975
TI  - Short duration transcranial direct current stimulation (tDCS) modulates verbal
      memory.
AB  - Transcranial direct current stimulation (tDCS) is a noninvasive method of
      modulating cortical excitability. The aim of this study was to investigate the
      effects of short-duration tDCS (1.6 seconds per trial) on memory performance, and
      whether the effects were affected by stimulation administered early or late in a
      trial. Participants memorize words under anodal and cathodal tDCS to the left
      dorsolateral prefrontal cortex (DLPFC) in two separate sessions in no
      stimulation, early stimulation, and late stimulation trials. Early stimulation
      occurred during word presentation, whereas late stimulation occurred after word
      presentation. Early anodal tDCS led to significantly better accuracy and speed in
      a subsequent recognition test compared to anodal late or no-stimulation
      conditions. Early cathodal tDCS, on the other hand, led to significantly worse
      accuracy and speed in a subsequent recognition test compared with cathodal late
      or no-stimulation conditions. The results of this study suggest that short
      duration tDCS can modulate memory performance and highlight the importance of
      period of stimulation.

PMID- 21962976
TI  - Bifrontal and bioccipital transcranial direct current stimulation (tDCS) does not
      induce mood changes in healthy volunteers: a placebo controlled study.
AB  - Transcranial direct current stimulation (tDCS) is the application of a weak
      electrical direct current (1.5 mA), which has the ability to modulate spontaneous
      firing rates of the cortical neurons by depolarizing or hyperpolarizing the
      neural resting membrane potential. tDCS in patients with depressive disorders has
      been proven to be an interesting therapeutic method potentially influencing
      pathologic mood states. Except one study, no alterations in mood could be
      confirmed applying tDCS in healthy participants. In this study, bifrontal or
      bioccipital stimulation was applied in 17 healthy subjects during 20 minutes with
      1.5 mA in a placebo-controlled manner. Bifrontal stimulation consisted of both
      anodal and cathodal placement on right and left dorsolateral prefrontal cortex
      (DLPFC) in two separate sessions. Using a set of self-reported moodscales (SUDS,
      POMS-32, PANAS, BISBAS) no significant mood changes could be observed, neither
      with bifrontal nor bioccipital tDCS. As already demonstrated by previous studies,
      we confirmed the minimal side effects and the safety of this neuromodulation
      technique.

PMID- 21962974
TI  - Effects of naltrexone and LY255582 on ethanol maintenance, seeking, and relapse
      responding by alcohol-preferring (P) rats.
AB  - Research indicates opioid antagonists can reduce alcohol drinking in rodents.
      However, tests examining the effects of opioid antagonists on ethanol seeking and
      relapse behavior have been limited. The present study examined the effects of two
      opioid antagonists on ethanol maintenance, seeking, and relapse responding by
      alcohol-preferring (P) rats. Adult P rats were self-trained in two-lever operant
      chambers to self-administer 15% (vol/vol) ethanol on a fixed-ratio 5 (FR5) versus
      water on a FR1 concurrent schedule of reinforcement in daily 1-h sessions. After
      10 weeks, rats underwent extinction training, followed by 2 weeks in their home
      cages. Rats were then returned to the operant chambers without ethanol or water
      to measure responses on the ethanol and water levers for four sessions. After a
      subsequent 2 weeks in the home cage, without access to ethanol, rats were
      returned to the operant chambers with ethanol and water available. Effects of
      antagonists on maintenance responding were tested after several weeks of daily 1
      h sessions. Naltrexone (NAL; 1-10mg/kg, subcutaneously [s.c.]; n=8/dose),
      LY255582 (LY; 0.03-1mg/kg, s.c.; n=8/dose), or vehicle were injected 30min before
      the first session (in the absence of ethanol), following 2 weeks in their home
      cages, and for four consecutive sessions of ethanol self-administration under
      maintenance and relapse conditions. Both NAL and LY reduced responses on the
      ethanol lever without any fluids present, and ethanol self-administration under
      relapse and on-going drinking conditions, with LY being more potent than NAL.
      Both NAL and LY were less effective in reducing responding in the absence of
      ethanol than in reducing ethanol self-administration. Overall, the results
      indicate that the opioid system is involved in mediating ethanol seeking, and
      ethanol self-administration under relapse and on-going alcohol drinking, but that
      different neurocircuits may underlie these behaviors.

PMID- 21962977
TI  - Modulation of cortical activity after anodal transcranial direct current
      stimulation of the lower limb motor cortex: a functional MRI study.
AB  - BACKGROUND AND OBJECTIVES: Functional magnetic resonance imaging (fMRI) has shown
      that transcranial direct current stimulation (tDCS) of the hand motor cortex
      modulates cortical activity of the healthy human brain. However, few studies have
      assessed the effects of tDCS on the leg motor cortex. We therefore used fMRI to
      examine the modulating effects of tDCS on lower limb motor cortex responses.
      METHODS: In this sham-controlled case-control study, 11 subjects were exposed to
      active anodal (n = 6) or sham (n = 5) stimulation, with the anode being
      positioned on the leg motor cortex of the right hemisphere. Each tDCS was
      delivered for 15 minutes at 2 mA, with each subject receiving a total of four
      stimulatory sessions on consecutive days. Cortical activity was measured before
      the first and after the fourth session by fMRI, and changes in cortical activity
      were calculated. RESULTS: Anodal tDCS increased activation of the ipsilateral
      supplementary motor area and lowered the extent of activation of both anterior
      cingulate gyri, the right middle and superior temporal gyri, the middle and
      superior frontal gyri, and the primary and secondary somatosensory cortices.
      CONCLUSIONS: Anodal tDCS increased corticospinal excitability of the lower limb
      motor cortex in healthy subjects, suggesting that multiple brain cortical areas
      may be associated with leg motor performance via involvement of variable
      corticocortical connections.

PMID- 21962978
TI  - Transcranial direct current stimulation in treatment resistant depression: a
      randomized double-blind, placebo-controlled study.
AB  - BACKGROUND: Anodal transcranial direct current stimulation (tDCS) of the
      prefrontal cortex has been proposed as therapeutic intervention in major
      depression. According to clinical needs, this study addresses the question
      whether tDCS is effective in treatment resistant major depressive episodes.
      METHODS: Twenty-two patients with a major depressive episode were randomly
      assigned to a cross-over protocol comparing tDCS and placebo stimulation add-on
      to a stable antidepressant medication. The parameters of active tDCS were: 1 or 2
      mA for 20 minutes/day, anode over the left dorsolateral prefrontal cortex,
      cathode over the contralateral supraorbital region. Active and placebo tDCS was
      applied for 2 weeks using indistinguishable DC stimulators. Patients, raters, and
      operators were blinded to treatment conditions. RESULTS: There was no significant
      difference in depression scores after 2 weeks of real compared with 2 weeks of
      sham tDCS. Scores on the Hamilton Depression Rating Scale were reduced from
      baseline by 14.7% for active tDCS and 10% for placebo tDCS. In contrast,
      subjective mood ratings showed an increase in positive emotions after real tDCS
      compared with sham tDCS. CONCLUSIONS: Anodal tDCS, applied for 2 weeks, was not
      superior to placebo treatment in patients with treatment resistant depression.
      However, secondary outcome measures are pointing to a positive effect of tDCS on
      emotions. Therefore, modified and improved tDCS protocols should be carried out
      in controlled pilot trials to develop tDCS towards an efficacious antidepressant
      intervention in therapy-resistant depression.

PMID- 21962979
TI  - Does second-scale intertrial interval affect motor evoked potentials induced by
      single-pulse transcranial magnetic stimulation?
AB  - OBJECTIVE: To determine whether a second-scale intertrial interval (ITI) of
      single-pulse transcranial magnetic stimulation (TMS) affects the measured
      amplitude of motor-evoked potentials (MEPs) representing individual corticospinal
      excitability. This was performed to challenge the common assumption of time
      invariance of such amplitudes. METHODS: Navigated TMS was used to map the
      dominant hemisphere of nine healthy subjects for the cortical representation
      focus of the contralateral thenar muscle, and resting motor threshold (MT) was
      determined. Single-trial MEP amplitudes were analyzed from trains of 30 responses
      induced at an intensity of 120% of the MT, and constant ITIs were investigated at
      1, 2, 3, 5, and 10 seconds as well as randomized at ranges of 1-3 seconds, 3-5
      seconds, and 5-10 seconds. MEP responses were divided into three blocks of 10
      consecutive responses within each stimulation train. Repeated samples ANOVA was
      used to assess whether the individual characteristic MEP amplitudes were time
      invariant, i.e., not affected by the different ITIs and stimulus blocks. RESULTS:
      The individual single-trial MEP amplitudes were affected significantly (P < 0.05)
      by the ITI (8/8 subjects), block number (5/8 subjects), and ITI by block number
      interaction (6/8 subjects). One subject was excluded as the sphericity of the
      variances could not be confirmed. Consequently, the found time variant nature of
      the individual single-trial MEP amplitudes affected the estimates (means) of
      individual characteristic MEP amplitudes. This was also observed as a significant
      block number effect (P < 0.05) across all subjects. CONCLUSIONS: The individual
      characteristic MEP amplitudes are time variant, contrary to the common
      assumption. Hence, individual characteristic MEP amplitude estimates should be
      used cautiously, as erroneous conclusions could be made when assuming those as
      time invariant.

PMID- 21962980
TI  - I-wave origin and modulation.
AB  - The human motor cortex can be activated by transcranial magnetic stimulation
      (TMS) evoking a high-frequency repetitive discharge of corticospinal neurones.
      The exact physiologic mechanisms producing the corticospinal activity still
      remain unclear because of the complexity of the interactions between the currents
      induced in the brain and the circuits of cerebral cortex, composed of multiple
      excitatory and inhibitory neurons and axons of different size, location,
      orientation and function. The aim of current paper is to evaluate whether the
      main characteristics of the activity evoked by single- and paired-pulse and
      repetitive TMS, can be accounted by the interaction of the induced currents in
      the brain with the key anatomic features of a simple cortical circuit composed of
      the superficial population of excitatory pyramidal neurons of layers II and III,
      the large pyramidal neurons in layer V, and the inhibitory GABA cells. This
      circuit represents the minimum architecture necessary for capturing the most
      essential cortical input-output operations of neocortex. The interaction between
      the induced currents in the brain and this simple model of cortical circuitry
      might explain the characteristics and nature of the repetitive discharge evoked
      by TMS, including its regular and rhythmic nature and its dose-dependency and
      pharmacologic modulation. The integrative properties of the circuit also provide
      a good framework for the interpretation of the changes in the cortical output
      produced by paired and repetitive TMS.

PMID- 21962982
TI  - Transcranial alternating stimulation in a high gamma frequency range applied over
      V1 improves contrast perception but does not modulate spatial attention.
AB  - Spatial visual attention enhances information processing within its focus. Vision
      at an attended location is faster, more accurate, of higher spatial resolution,
      and has an enhanced sensitivity for fine changes. Earlier hypotheses suggest that
      the neuronal mechanisms of these processes are based on the interactions among
      different neuronal groups by means of cortical oscillations in the gamma range.
      The aim of the current study was to modulate these oscillations externally, using
      a new technique called transcranial alternating current stimulation (tACS). We
      investigated the effect of covert spatial attention within and outside its focus
      by probing contrast sensitivity and contrast discrimination at high resolution
      across the visual field of 20 healthy human subjects. While applying 40, 60, and
      80 Hz tAC stimulation over the primary visual cortex (V1), subjects' contrast
      discrimination thresholds were obtained using two different conditions: in the
      first condition we presented a black disc as a peripheral cue that automatically
      attracted the subject's attention, whereas there was no cue in the second
      condition. We found that the spatial profile of contrast sensitivity was not
      affected by the stimulation. Contrast-discrimination thresholds on the other hand
      decreased significantly during 60 Hz tACS, whereas there was no effect of 40 and
      80 Hz stimulation. These results suggest that attention plays an important role
      in contrast discrimination based on V1 activities that are influences by gamma
      range tACS stimulation.

PMID- 21962983
TI  - A computational model of direct brain excitation induced by electroconvulsive
      therapy: comparison among three conventional electrode placements.
AB  - BACKGROUND: Electroconvulsive therapy (ECT) is a highly effective treatment for
      severe depressive disorder. Efficacy and cognitive outcomes have been shown to
      depend on variations in electrode placement and other stimulus parameters,
      presumably because of differences in the pattern of neuronal activation. This
      latter effect, however, is poorly understood. OBJECTIVE: In this study, we
      present an anatomically accurate human head computational model to stimulate
      neuronal excitation during ECT, to better understand the effects of varying
      electrode placement and stimulus parameters. METHODS: Electric field and current
      density throughout the head, as well as direct neural activation within the
      brain, were computed using the finite element method. Regions representing
      passive volume conductors (skin, skull, cerebrospinal fluid) were extracellularly
      coupled to an excitable neural continuum region representing the brain. The skull
      was modeled with anistropic electrical conductivity. RESULTS: Simulation results
      indicated that direct activation of the brain occurred immediately beneath the
      electrodes on the scalp, consistent with existing imaging studies. In addition,
      we found that the brainstem was also activated using a right unilateral electrode
      configuration. Simulation also demonstrated that a reduction in stimulus
      amplitude or pulse width led to a reduction in the spatial extent of brain
      activation. CONCLUSIONS: The novel model described in this study was able to
      simulate direct excitation of the brain during ECT, was useful in characterizing
      differences in neuronal activation as electrode placement, pulse width, and
      amplitude were altered, and is proposed as a tool for further exploring the
      effects of variations in ECT stimulation approaches. Results from the simulations
      assist in understanding recently described clinical phenomena, in particular, the
      reduction in cognitive side effects with ultrabrief pulse width stimulation, and
      greater effects of the ECT stimulus on cardiovascular function with unilateral
      electrode placement.

PMID- 21962981
TI  - Modulation of large-scale brain networks by transcranial direct current
      stimulation evidenced by resting-state functional MRI.
AB  - BACKGROUND: Brain areas interact mutually to perform particular complex brain
      functions such as memory or language. Furthermore, under resting-state conditions
      several spatial patterns have been identified that resemble functional systems
      involved in cognitive functions. Among these, the default-mode network (DMN),
      which is consistently deactivated during task periods and is related to a variety
      of cognitive functions, has attracted most attention. In addition, in resting
      state conditions some brain areas engaged in focused attention (such as the
      anticorrelated network, AN) show a strong negative correlation with DMN; as task
      demand increases, AN activity rises, and DMN activity falls. OBJECTIVE: We
      combined transcranial direct current stimulation (tDCS) with functional magnetic
      resonance imaging (fMRI) to investigate these brain network dynamics. METHODS:
      Ten healthy young volunteers underwent four blocks of resting-state fMRI (10
      minutes), each of them immediately after 20 minutes of sham or active tDCS (2
      mA), on two different days. On the first day the anodal electrode was placed over
      the left dorsolateral prefrontal cortex (DLPFC) (part of the AN) with the cathode
      over the contralateral supraorbital area, and on the second day, the electrode
      arrangement was reversed (anode right-DLPFC, cathode left-supraorbital). RESULTS:
      After active stimulation, functional network connectivity revealed increased
      synchrony within the AN components and reduced synchrony in the DMN components.
      CONCLUSIONS: Our study reveals a reconfiguration of intrinsic brain activity
      networks after active tDCS. These effects may help to explain earlier reports of
      improvements in cognitive functions after anodal-tDCS, where increasing cortical
      excitability may have facilitated reconfiguration of functional brain networks to
      address upcoming cognitive demands.

PMID- 21962984
TI  - Perceptual improvement following repetitive sensory stimulation depends
      monotonically on stimulation intensity.
AB  - BACKGROUND: Electrical repetitive sensory stimulation (rSS) is a direct and
      effective means of inducing plasticity processes in human beings, and is
      increasingly being used as a therapeutic intervention. Suprathreshold intensities
      induce beneficial effects on tactile perception and sensorimotor abilities.
      However, it is not known whether there is an optimal range of stimulus intensity.
      METHODS: We investigated the effect of varied intensities (low, 1.19 +/- 0.07 mA;
      intermediate, 3.33 +/- 0.27 mA; and high, 4.42 +/- 0.56 mA) on the outcome of a
      30-minute electrical rSS applied to the index finger (intermittent high-frequency
      stimulation, 20 Hz and interburst interval, 5 seconds) in three groups (n = 10
      each) of participants. As a marker of perceptual changes, we measured tactile
      spatial two-point discrimination on the stimulated finger and on the heel of the
      hand before and after the rSS. RESULTS: rSS improved discrimination performance,
      with the gain being the highest in the high-intensity group and the lowest in the
      low-intensity group. Measurements on the heel of the hand revealed small
      improvements in the high-intensity group, indicative of recruitment processes.
      CONCLUSIONS: rSS of maximal intensity induced the strongest effects, indicative
      of a monotonic intensity-gain characteristic with no U-shaped dependency.

PMID- 21962985
TI  - Impact of altered venous hemodynamic conditions on the formation of platelet
      layers in thromboemboli.
AB  - Although it is generally believed that the structure of venous thromboemboli is a
      homogeneous red blood cell-fibrin clot, their structure may be heterogeneous,
      with non-uniformly distributed platelet layers, known as the lines of Zahn. We
      tested (a) whether venous thromboemboli ex vivo contained platelet layers, i.e.
      the lines of Zahn, and (b) whether, according to mathematical modeling, eddies
      can arise in the venous system, possibly contributing to platelet aggregation.
      The structure of venous thromboemboli ex vivo was determined by high-resolution
      magnetic resonance imaging (MRI) and by immunohistochemistry (IHC). High
      resolution ultrasound (US) imaging was employed to determine the popliteal vein
      geometry and hemodynamics in healthy subjects and in subjects with previous
      venous thrombosis. The US data were then used as input for numerical simulations
      of venous hemodynamics. MRI and IHC confirmed that 42 of 49 ex vivo venous
      thromboemboli were structurally heterogeneous with platelet layers. The peak
      venous flow velocity was higher in patients with partly recanalized deep vein
      thrombosis than in healthy subjects in the prone position (46+/-4cm/s vs. 16+/
      3cm/s). Our numerical simulation showed that partial venous obstruction with
      stenosis or malfunctioning venous valves creates the conditions for eddy blood
      flow. Our experimental results and computer simulation confirmed that the
      heterogeneous structure of venous thromboemboli with twisted platelet layers may
      be associated with eddy flow at the sites of their formation.

PMID- 21962986
TI  - Postprandial changes in the phospholipid composition of circulating
      microparticles are not associated with coagulation activation.
AB  - INTRODUCTION: Evidence is present that the phospholipid composition of
      circulating cell-derived microparticles (MP) affects coagulation in vivo, and
      that postprandial metabolic alterations may be associated with hypercoagulable
      state. Our objective was to investigate whether postprandial metabolic responses
      affect the phospholipid composition of MP, and whether such changes are
      associated with coagulation activation. MATERIALS AND METHODS: Twelve healthy
      males were studied twice and randomly received two consecutive meals or remained
      fasted. Blood was collected before and at 2, 4, 6 and 8h following breakfast.
      Plasma concentrations of prothrombin-F(1+2) and thrombin-antithrombin-complexes
      were measured. Numbers and cellular origin of MP were determined by
      flowcytometry. The phospholipid composition of MP was determined by hpTLC. In
      vitro procoagulant activity of MP was studied by fibrin generation. RESULTS:
      During the meal visit, plasma glucose, triglyceride and insulin levels increased,
      compared to baseline and the fasting visit (all P<0.05). Postprandially, the
      total numbers of MP increased in time compared to the fasting visit (P<0.05).
      Erythrocyte-derived MP increased (6-fold) during the meal visit, but remained
      constant on the fasting day (P<0.001). On the meal versus fasting day circulating
      MP contained increased phosphatidylcholine (P<0.05) and decreased sphingomyelin
      (P<0.05) amounts. The amount of phosphatidylserine did not change. Concentrations
      of plasma F(1+2) and thrombin-antithrombin were similar on both days, as was the
      ability of MP to generate fibrin in vitro. CONCLUSION: Although numbers, cellular
      origin and phospholipid composition of MP alter during exposure to two
      consecutive meals in healthy subjects, this does not lead to changes in the
      coagulation activation in vivo.

PMID- 21962987
TI  - Synthesis, molecular modeling and preliminary biological evaluation of a set of 3
      acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazole as potential antibacterial,
      anti-Trypanosoma cruzi and antifungal agents.
AB  - A series of 3-acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazole derivatives
      was synthesized and their activity screened in vitro against Staphylococcus
      aureus, Trypanosoma cruzi, and Candida albicans. The bioactivity was expressed as
      minimum inhibitory concentration (MIC) for S. aureus strains, and as fifty
      percent inhibitory concentration (IC(50)) of parasite population growth for T.
      cruzi. A molecular modeling approach was performed to establish qualitative
      relationships regarding the biological data and the compounds' physicochemical
      properties. The 5-(4-OC(4)H(9)Ph, 5l), and 5-(4-CO(2)CH(3)Ph, 5o) derivatives
      were the most active compounds for S. aureus ATCC 25923 (MIC=1.95-1.25 MUg/mL)
      and T. cruzi (IC(50)=7.91 MUM), respectively. Also, a preliminary evaluation
      against C. albicans involving some compounds was performed and the 5-(4-CH(3)Ph,
      5e) derivative was the most active compound (MIC=3.28-2.95 MUg/mL). In this
      preliminary study, all synthesized 3-acetyl-2,5-disubstituted-2,3-dihydro-1,3,4
      oxadiazole derivatives were active against all microorganisms tested.

PMID- 21962988
TI  - Design, synthesis and biological evaluation of mannosyl triazoles as FimH
      antagonists.
AB  - Urinary tract infection (UTI) caused by uropathogenic Escherichia coli (UPEC) is
      one of the most prevalent infectious diseases. Particularly affected are women,
      who have a 40-50% risk to experience at least one symptomatic UTI episode at some
      time during their life. In the initial step of the infection, the lectin FimH,
      located at the tip of bacterial pili, interacts with the high-mannosylated
      uroplakin Ia glycoprotein on the urinary bladder mucosa. This interaction is
      critical for the ability of UPEC to colonize and invade the bladder epithelium. X
      ray structures of FimH co-crystallized with two different ligands, the
      physiological binding epitope oligomannose-3 and the antagonist biphenyl alpha-D
      mannoside 4a revealed different binding modes, an in-docking-mode and an out
      docking-mode, respectively. To accomplish the in-docking-mode, that is the
      docking mode where the ligand is hosted by the so-called tyrosine gate, FimH
      antagonists with increased flexibility were designed and synthesized. All
      derivatives 5-8 showed nanomolar affinities, but only one representative, the 4
      pyridiyl derivative 5j, was as potent as the reference compound n-heptyl alpha-D
      mannoside (1b). Furthermore, a loss of affinity was observed for C-glycosides and
      derivatives where the triazole aglycone is directly N-linked to the anomeric
      center. A conformational analysis by NMR revealed that the triazolyl-methyl-C
      mannosides 8 adopt an unusual (1)C(4) chair conformation, explaining the
      comparably lower affinity of these compounds. Furthermore, to address the
      druglikeness of this new class of FimH antagonists, selected pharmacokinetic
      parameters, which are critical for oral bioavailability (lipophilicity,
      solubility, and membrane permeation), were determined.

PMID- 21962989
TI  - Tubercular gastroduodenal abscess presenting with obstructive jaundice: diagnosis
      with EUS-guided FNA.

PMID- 21962990
TI  - Identification of amino acid residues of a designed ankyrin repeat protein
      potentially involved in intermolecular interactions with CD4: analysis by
      molecular dynamics simulations.
AB  - We applied molecular dynamics simulations to investigate the binding properties
      of a designed ankyrin repeat protein, the DARPin-CD4 complex. DARPin 23.2 has
      been reported to disturb the human immunodeficiency virus (HIV) viral entry
      process by Schweizer et al. The protein docking simulation was analysed by
      comparing the specific ankyrin binder (DARPin 23.2) to an irrelevant control
      (2JAB) in forming a composite with CD4. To determine the binding free energy of
      both ankyrins, the MM/PBSA and MM/GBSA protocols were used. The free energy
      decomposition of both complexes were analysed to explore the role of certain
      amino acid residues in complex configuration. Interestingly, the molecular
      docking analysis of DARPin 23.2 revealed a similar CD4 interaction regarding the
      gp120 theoretical anchoring motif. In contrast, the binding of control ankyrin to
      CD4 occurred at a different location. This observation suggests that there is an
      advantage to the molecular modification of DARPin 23.2, an enhanced affinity for
      CD4.

PMID- 21962991
TI  - Interrupting IL-6-receptor signaling improves atopic dermatitis but associates
      with bacterial superinfection.

PMID- 21962992
TI  - Uptake of blood coagulation factor VIII by dendritic cells is mediated via its C1
      domain.
AB  - BACKGROUND: The uptake and processing of blood coagulation factor VIII (FVIII) by
      antigen-presenting cells and the subsequent presentation of FVIII-derived
      peptides to CD4(+) T cells direct the immune response to FVIII in patients with
      hemophilia A. Multiple receptors including mannose receptor and low-density
      lipoprotein receptor-related protein-1 (LRP1) have been implicated in FVIII
      uptake. OBJECTIVE: This work studies the involvement of receptor candidates in
      FVIII uptake by dendritic cells (DCs). Furthermore, we explore FVIII residues
      that mediate endocytosis. METHODS: FVIII uptake was performed with human monocyte
      derived and murine bone marrow-derived DCs. To investigate FVIII endocytosis,
      competition assays with soluble receptor ligands, binding studies with
      recombinant receptor fragments, and small-interfering RNA-induced gene silencing
      were performed. In addition, FVIII-targeting monoclonal antibodies KM33 and VK34
      were used. To confirm in vitro results, hemophilic E17 knockout mice were
      pretreated with antibodies prior to FVIII injections and anti-FVIII titers were
      determined. RESULTS: Upon treatment of DCs with mannan or LRP ligand alpha2
      macroglobulin, we observed only a minor decrease in FVIII internalization. In
      addition, small interfering RNA-mediated knockdown of LRP, mannose receptor, or
      DC-SIGN expression in monocyte-derived dendritic cells did not prevent FVIII
      uptake. Binding studies using Fc chimeras revealed that LRP, DC-SIGN, and mannose
      receptor can bind to FVIII; however, we did not observe a critical role for these
      receptors in FVIII uptake. Previous studies have shown that human antibodies
      targeting the C1 (KM33) and A2 (VK34) domains of FVIII interfere with binding to
      endocytic receptors. Preincubation of FVIII with VK34 did not influence FVIII
      uptake; however, KM33 completely inhibited FVIII endocytosis by both monocyte
      derived dendritic cells and bone marrow-derived dendritic cells. Accordingly,
      anti-FVIII antibody titers were greatly reduced following the preadministration
      of KM33 in vivo. CONCLUSION: Together, our observations emphasize the
      physiological significance of KM33-targeted residues within the C1 domain in the
      uptake of FVIII by DCs in vitro and in vivo.

PMID- 21962993
TI  - Usefulness of high-sensitivity C-reactive protein to predict mortality in
      patients with atrial fibrillation (from the Atherosclerosis Risk In Communities
      [ARIC] Study).
AB  - High-sensitivity C-reactive protein (hs-CRP) is a marker for the risk of
      cardiovascular and overall mortality. However, information about the association
      between hs-CRP and mortality in patients with atrial fibrillation is scarce. A
      total of 293 participants of the Atherosclerosis Risk In Communities study with a
      history of AF and hs-CRP levels available were studied. During a median follow-up
      of 9.4 years, 134 participants died (46%). The hazard ratio of all-cause
      mortality associated with the highest versus the lowest tertile of hs-CRP was
      2.52 (95% confidence interval 1.49 to 4.25) after adjusting for age, gender,
      history of cardiovascular diseases, and cardiovascular risk factors. A similar
      trend was observed for cardiovascular mortality (57 events; hazard ratio 1.90,
      95% confidence interval 0.81 to 4.45). The Congestive heart failure,
      Hypertension, Age >75 years, Diabetes, and previous Stroke or transient ischemic
      attack (CHADS2) score was also associated with all-cause and cardiovascular
      mortality, with an adjusted hazard ratio of 3.39 (95% confidence interval 1.91 to
      6.01) and 8.71 (95% confidence interval 2.98 to 25.47), respectively, comparing
      those with a CHADS2 score >2 versus a CHADS2 score of 0. Adding hs-CRP to a
      predictive model including the CHADS2 score was associated with an improvement of
      the C-statistic for total mortality (from 0.627 to 0.677) and for cardiovascular
      mortality (from 0.700 to 0.718). In conclusion, high levels of hs-CRP constitute
      an independent marker for the risk of mortality in patients with atrial
      fibrillation.

PMID- 21962994
TI  - Association between bleeding severity and long-term mortality in patients
      experiencing vascular complications after percutaneous coronary intervention.
AB  - Vascular complications (VCs) occur in 3% to 8% of percutaneous coronary
      interventions (PCIs). However, only a portion of patients who experience VCs
      bleed significantly. The aim of this study was to assess the covariates
      associated with the amount of blood loss in patients experiencing postprocedural
      VCs as well as the effect of the degree of blood loss on long-term mortality.
      Overall, 7,718 unselected patients who underwent PCI through femoral access were
      evaluated. Those experiencing VCs were identified and stratified with regard to
      the degree of hematocrit (HCT) decrease after the procedure. In total, 444
      patients (5.8%) had VCs. Compared to those without VCs, patients with VCs were
      older and had more extensive co-morbidities. Severe blood loss was most frequent
      in those who had vascular perforation requiring surgical repair or in those who
      had retroperitoneal bleeding. Overall, <25% of patients with hematoma had severe
      blood loss. The raw 1-year mortality was doubled in patients with minimal or
      moderate HCT decrease and was tripled in those with severe decreases in HCT.
      Similarly, the rate of definite stent thrombosis was tripled in patients with VCs
      and moderate or severe decreases in HCT. After adjustment, only patients with VCs
      and the greater HCT decreases had an increased risk for death at 1 year (hazard
      ratio 1.80, 95% confidence interval 1.03 to 3.14). Independent predictors of
      severe HCT decrease included age, female gender, glycoprotein IIb/IIIa inhibitor
      use, and activated clotting time peak. Bivalirudin and closure devices were
      independently associated with less frequent severe HCT decrease. In conclusion,
      VCs do not entail an increased risk for death at 1 year unless associated with
      severe blood loss. The use of bivalirudin and closure devices seems to reduce the
      risk for such complications.

PMID- 21962995
TI  - Exposure to low-dose ionizing radiation from cardiac imaging among patients with
      myocardial infarction.
AB  - Patients with first acute myocardial infarction (AMI) constitute a demographic
      that is exposed to significant amounts of low-dose ionizing radiation (LDIR) over
      a short period. The aim of this study was to describe cardiac LDIR exposure
      trends among patients with first AMI over a recent approximately 10-year period.
      Administrative databases were used to identify a cohort of 106,803 patients who
      had first AMIs in Quebec, Canada, from 1996 to 2004. These patients were followed
      through 2007, and the use over time of cardiac imaging procedures associated with
      LDIR was documented using a cumulative exposure variable. Exposure was documented
      in 2 periods: the acute phase (<1 month after AMI) and the chronic phase (1 month
      to 3 years after AMI). The mean dose of cardiac LDIR incurred in the acute post
      AMI phase increased twofold during the study period, from 6.8 to 11.8
      mSv/patient. However, the mean dose of cardiac LDIR incurred in the chronic post
      AMI phase decreased, from 8.3 to 7.3 mSv/patient. Overall, there was a 26.4%
      increase in cumulative cardiac LDIR exposure, to a mean of 19.1 mSv/patient in
      the 2 years after AMI, which was driven primarily by an increase in percutaneous
      coronary interventions. When patients were stratified by cumulative LDIR
      exposure, several predictors of heavier LDIR exposure were identified among the
      strata of exposed patients, including younger age and the absence of acute and co
      morbid conditions, and the heaviest exposed group subsequently had the lowest
      overall mortality. In conclusion, among patients experiencing first AMI in
      Canada, exposure to cardiac LDIR increased over a recent approximately 10-year
      period. However, the observed trend is toward increasing use of therapeutic
      procedures with proven mortality benefit undertaken earlier in the disease course
      and away from diagnostic procedures in the subsequent years after AMI.

PMID- 21962996
TI  - Analysis of target lesion length before coronary artery stenting using
      angiography and near-infrared spectroscopy versus angiography alone.
AB  - Lipid core plaque (LCP) can extend beyond the angiographic margins of a target
      lesion, potentially resulting in incomplete lesion coverage. We sought to compare
      the target lesion length using near-infrared spectroscopy (NIRS) combined with
      conventional coronary angiography versus angiography alone. NIRS was performed in
      69 patients (75 lesions) undergoing native vessel percutaneous coronary
      intervention (LipiScan Coronary Imaging System). Chemograms were analyzed for the
      presence and location of LCP, either within or extending beyond, the angiographic
      margins of the target lesion. The target lesion length was measured by
      quantitative coronary angiography (QCA) and compared to the lesion length
      measured using QCA and NIRS. LCP was present in 50 target lesions (67%). In 42
      lesions (84%), LCP was present only within the target lesion. In 8 lesions (16%)
      LCP extended beyond the angiographic margins of the lesion. Of these 8 lesions, 4
      (8%) had LCP <=5 mm from the margins, and 4 lesions (8%) had LCP >5 mm from the
      angiographic margins. The mean distance that the LCP extended beyond the
      angiographic lesion margin was 7 +/- 4 mm (range 2 to 14). For these 8 lesions,
      the target lesion length with NIRS plus QCA was 28 +/- 10 mm versus 21 +/- 8 mm
      with QCA alone. In conclusion, patients undergoing coronary artery stenting could
      have LCP extending beyond the intended treatment margins as defined using QCA
      alone. This could have implications for stent length selection and optimal lesion
      coverage.

PMID- 21962997
TI  - Relation of fragmented QRS complex to right ventricular fibrosis detected by late
      gadolinium enhancement cardiac magnetic resonance in adults with repaired
      tetralogy of fallot.
AB  - Fragmented QRS (fQRS) on 12-lead electrocardiography reflects conduction delay
      caused by myocardial fibrosis and dysfunction. Ventricular fibrosis detected by
      late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) is reportedly
      correlated with worse clinical outcomes in adults with repaired tetralogy of
      Fallot (TOF). The aim of this study was to assess whether the presence of fQRS is
      associated with right ventricular (RV) fibrosis or dysfunction in this patient
      group. In 37 consecutive patients (median age 30 years, median age at repair 6.6
      years), the number of leads showing fQRS, defined as the presence of >2 notches
      on the R/S wave in >=2 contiguous leads, was counted. RV systolic function,
      dilatation, and LGE score were measured using LGE CMR. Ventricular LGE was
      observed mainly at the previous surgical sites: the RV outflow tract (33 of 37),
      ventricular septal defect patch region (15 of 37), and RV anterior wall (11 of
      37). Fragmented QRS was found mostly in the right and mid precordial leads. The
      fQRS group (n = 20) demonstrated higher RV LGE scores (p <0.001) and lower RV
      ejection fractions (p = 0.02) and a trend toward larger RV end-diastolic and end
      systolic volumes (p = 0.12 and p = 0.06, respectively) compared to the non-fQRS
      group (n = 17). The number of electrocardiographic leads showing fQRS was
      positively correlated with RV LGE score (r = 0.75, p <0.001). The presence of
      fQRS remained independently associated with the presence of supramedian RV LGE
      score, even after adjusting for relevant parameters. In conclusion, fQRS was
      closely associated with more extensive RV fibrosis and dysfunction in adults with
      repaired tetralogy of Fallot.

PMID- 21962998
TI  - Out-of-hospital deaths within 30 days following hospitalization where
      percutaneous coronary intervention was performed.
AB  - Much has been learned about predictors of in-hospital death after percutaneous
      coronary intervention (PCI), but little is known about the predictors of short
      term death after discharge. This is particularly important for PCI, with its
      short postprocedural hospitalization and concern about postprocedural events such
      as stent thrombosis and need for emergency cardiac surgery. The focus of this
      study was all 51,695 patients who underwent PCI in New York State from January 1,
      2007, and December 31, 2007, who were discharged alive by December 31, 2007. All
      patients were followed for 30 days after discharge to determine if they died
      after discharge within 30 days. The in-hospital and 30-day mortality rate for PCI
      patients was 0.94%, the in-hospital mortality rate was 0.56%, and the mortality
      rate for deaths that occurred after discharge within 30 days of the procedure was
      0.38%. Of the PCI deaths that occurred either in the index admission or after
      discharge within 30 days, 40.5% occurred after discharge. The percentage of short
      term (in-hospital or within 30 days) deaths in hospitals with >=10 short-term
      deaths ranged from 15% to 71%. In conclusion, compared to PCI patients dying in
      the index admission, patients who died <30 days after discharge were younger, had
      better ventricular function, were less likely to have had recent myocardial
      infarctions, and were less likely to have had postprocedural complications. Most
      deaths in the 30-day group were cardiovascular, and most were cardiac and acute.
      A small percentage were related to chronic cardiac disease or to vascular
      disease.

PMID- 21962999
TI  - Association between having a caregiver and clinical outcomes 1 year after
      hospitalization for cardiovascular disease.
AB  - Caregivers might represent an opportunity to improve cardiovascular disease
      outcomes, but prospective data are limited. We studied 3,188 consecutive patients
      (41% minority, 39% women) admitted to a university hospital medical
      cardiovascular service to evaluate the association between having a caregiver and
      rehospitalization/death at 1 year. The clinical outcomes at 1 year were
      documented using a hospital-based clinical information system supplemented by a
      standardized questionnaire. Co-morbidities were documented by hospital electronic
      record review. At baseline, 13% (n = 417) of the patients had a paid caregiver
      and 25% (n = 789) had only an informal caregiver. Having a caregiver was
      associated with rehospitalization or death at 1 year (odds ratio [OR] 1.68, 95%
      confidence interval [CI] 1.45 to 1.95), which varied by paid (OR 2.46, 95% CI
      1.96 to 3.09) and informal (OR 1.40, 95% CI 1.18 to 1.65) caregiver status.
      Having a caregiver was significantly (p <0.05) associated with age >=65 years,
      racial/ethnic minority, lack of health insurance, medical history of diabetes
      mellitus or hypertension, a Ghali co-morbidity index >1, chronic obstructive
      pulmonary disease, or taking >=9 prescriptions medications. The relation between
      caregiving and rehospitalization/death at 1 year was attenuated but remained
      significant after adjustment (paid, OR 1.64, 95% CI 1.26 to 2.12; and informal,
      OR 1.20, 95% CI 1.00 to 1.44). In conclusion, the risk of rehospitalization/death
      was significantly greater among cardiac patients with caregivers and was not
      fully explained by the presence of traditional co-morbidities. Systematic
      determination of having a caregiver might be a simple method to identify patients
      at a heightened risk of poor clinical outcomes.

PMID- 21963000
TI  - Shotgun wound and pellet embolism to the intracranial carotid artery.
AB  - Missile embolism into the cerebral circulation is a very unusual complication of
      shotgun wounds to the chest or neck. We report a case of an 11-year-old boy who
      sustained an air gunshot wound and pellet embolism to the intracranial carotid
      artery. The cerebral artery pellet embolus resulted in contralateral hemiplegia.
      The patient was successfully treated by emergency flow reversal and embolectomy.
      Because this injury is extremely rare, the literature is reviewed, and several
      principles are suggested to improve the management.

PMID- 21963001
TI  - Carotid artery aneurysms in patients with human immunodeficiency virus.
AB  - OBJECTIVES: Carotid artery aneurysms, although rare, are increasing in frequency
      due to their association with human immunodeficiency virus (HIV) disease. Our
      institution serves a population with a high HIV prevalence and we wished to
      document our growing experience with this aneurysmal pathology in a setting of an
      ever-increasing burden of HIV disease. METHODS: Data on all patients managed at
      Inkosi Albert Luthuli Central Hospital in Durban, South Africa, from July 2003 to
      December 2009 with HIV carotid aneurysms were extracted from a prospective
      vascular database and their case records were examined. Twenty-two patients were
      identified of whom 21 had preoperative imaging and underwent some form of
      intervention. RESULTS: The initial presentation in 19 of the 22 patients was a
      progressively enlarging neck mass and pain. Ten patients presented with neurology
      with only 1 patient presenting with a hemiplegia and 1 patient with a monoplegia.
      Sixteen patients had an open operative repair and 5 patients had an endovascular
      repair performed as the initial procedure. Of the open procedure, 8 patients had
      an interposition graft used and 8 had ligation of the common carotid artery
      (CCA), external carotid artery (ECA), and/or internal carotid artery (ICA).
      Eighteen patients had no immediate postoperative neurological complications. The
      worst outcomes were from patients who underwent an endovascular procedure. These
      included one death, two thrombosed stents, and one endoleak. Histology showed
      active tuberculosis (TB) in 6 patients who were not known to have TB
      preoperatively. The overall mortality was 3 of 22 patients. CONCLUSION: We have
      noted aneurysms of the carotid artery to occur in patients who are infected with
      HIV and it seems to be that the incidence of such aneurysms is more common than
      documented. Open surgical intervention either in the form of an interposition
      graft or ligation seems to be the more effective treatment option as compared to
      endovascular stenting. Stenting should be reserved for those patients unfit for
      open surgery.

PMID- 21963002
TI  - Comparison of stratified primary care management for low back pain with current
      best practice (STarT Back): a randomised controlled trial.
AB  - BACKGROUND: Back pain remains a challenge for primary care internationally. One
      model that has not been tested is stratification of the management according to
      the patient's prognosis (low, medium, or high risk). We compared the clinical
      effectiveness and cost-effectiveness of stratified primary care (intervention)
      with non-stratified current best practice (control). METHODS: 1573 adults (aged
      >=18 years) with back pain (with or without radiculopathy) consultations at ten
      general practices in England responded to invitations to attend an assessment
      clinic. Eligible participants were randomly assigned by use of computer-generated
      stratified blocks with a 2:1 ratio to intervention or control group. Primary
      outcome was the effect of treatment on the Roland Morris Disability Questionnaire
      (RMDQ) score at 12 months. In the economic evaluation, we focused on estimating
      incremental quality-adjusted life years (QALYs) and health-care costs related to
      back pain. Analysis was by intention to treat. This study is registered, number
      ISRCTN37113406. FINDINGS: 851 patients were assigned to the intervention (n=568)
      and control groups (n=283). Overall, adjusted mean changes in RMDQ scores were
      significantly higher in the intervention group than in the control group at 4
      months (4.7 [SD 5.9] vs 3.0 [5.9], between-group difference 1.81 [95% CI 1.06
      2.57]) and at 12 months (4.3 [6.4] vs 3.3 [6.2], 1.06 [0.25-1.86]), equating to
      effect sizes of 0.32 (0.19-0.45) and 0.19 (0.04-0.33), respectively. At 12
      months, stratified care was associated with a mean increase in generic health
      benefit (0.039 additional QALYs) and cost savings (L240.01 vs L274.40) compared
      with the control group. INTERPRETATION: The results show that a stratified
      approach, by use of prognostic screening with matched pathways, will have
      important implications for the future management of back pain in primary care.
      FUNDING: Arthritis Research UK.

PMID- 21963003
TI  - Management of low back pain in primary care: a new approach.

PMID- 21963005
TI  - Enhancing adherence to produce consumption: health benefits abound.

PMID- 21963004
TI  - Effective tobacco control is key to rapid progress in reduction of non
      communicable diseases.

PMID- 21963006
TI  - Planning for the future: as an organization and as individuals.

PMID- 21963007
TI  - Reentering the dietetics profession: FAQ.

PMID- 21963008
TI  - Satisfying customers and lowering costs in foodservice: can both be accomplished
      simultaneously?

PMID- 21963009
TI  - Clarification of DRIs for calcium and vitamin D across age groups.

PMID- 21963010
TI  - Is anemia in WHI-OS related to calcium supplement use?

PMID- 21963012
TI  - Understanding the behavioral linkages needed for designing effective
      interventions to increase fruit and vegetable intake in diverse populations.

PMID- 21963013
TI  - Moving beyond diet and colorectal cancer.

PMID- 21963014
TI  - Fruit and vegetable consumption and the risk of proximal colon, distal colon, and
      rectal cancers in a case-control study in Western Australia.
AB  - BACKGROUND: Fruits and vegetables (F/V) have been examined extensively in
      nutrition research in relation to colorectal cancer (CRC). However, their
      protective effect is subject to debate, possibly because of different effects on
      different subsites of the large bowel. OBJECTIVE: To determine whether any
      association between F/V consumption and risk of CRC differed by subsite of the
      bowel (proximal colon, distal colon, and rectum). DESIGN: The Western Australian
      Bowel Health Study is a population-based, case-control study conducted between
      June 2005 and August 2007. Complete food frequency questionnaire data were
      analysed from 834 CRC cases and 939 controls. Logistic regression analysis was
      used to estimate the effects of quartiles of F/V intake on risk of CRC at
      different subsites. Odds ratios (OR) and 95% confidence intervals (CI) were
      calculated for CRC overall and for the three separate subsites. RESULTS: Risk of
      proximal colon cancer and rectal cancer was not associated with intakes of total
      F/V, total vegetable, or total fruit. Brassica vegetable intake was inversely
      related with proximal colon cancer (Q4 vs Q1 OR 0.62; 95% CI 0.41 to 0.93). For
      distal colon cancer, significant negative trends were seen for total F/V, and
      total vegetable intake. Distal colon cancer risk was significantly decreased for
      intake of dark yellow vegetables (Q4 vs Q1 OR 0.61; 95% CI 0.41 to 0.92) and
      apples (Q4 vs Q1 OR 0.51; 95% CI 0.34 to 0.77). An increased risk for CRC was
      found to be associated with intake of fruit juice (Q4 vs Q1 OR 1.74; 95% CI 1.24
      to 2.45). CONCLUSIONS: Our results suggest that different F/V may confer
      different risks for cancer of the proximal colon, distal colon, or rectum. Future
      studies might consider taking into account the location of the tumor when
      examining the relation between F/V consumption and risk of CRC.

PMID- 21963015
TI  - Relationship between home fruit and vegetable availability and infant and
      maternal dietary intake in African-American families: evidence from the
      exhaustive home food inventory.
AB  - BACKGROUND: The availability of foods in the home is likely to be related to
      consumption. We know of no studies that have reported this association in African
      American participants, and few studies have examined home food availability using
      objective methods. OBJECTIVE: This study aimed to assess the association between
      objective measures of fruits and vegetables in the home with reported infant and
      maternal diet in low-income African Americans. DESIGN: A cross-sectional study
      design was used to compare food availability and dietary intake. The Exhaustive
      Home Food Availability Inventory used barcode scanning to measure food
      availability in the home. Maternal and infant diet was assessed by 24-hour
      recall. SUBJECTS/SETTING: Eighty African-American first-time mother/infant dyads
      were recruited from Wake and Durham counties in North Carolina. STATISTICAL
      ANALYSES PERFORMED: Adjusted mean dietary intake of infants and mothers was
      calculated within tertiles of food and nutrient availability using analysis of
      variance. The bootstrap method was used to estimate P values and 95% confidence
      intervals. Models were adjusted for mother's age, household size, shopping and
      eating-out behavior. RESULTS: Infants and mothers living in homes in the highest
      tertile of availability of energy, nutrients, and fruits and vegetables tended to
      have the highest consumption, respectively; however, statistically significant
      associations were more likely to occur with infant diet than maternal diet. The
      relationship was strongest for infant consumption of fruit, with an average of
      103.3 g consumed by infants who lived in homes in the highest tertile of
      availability, compared to 42.5 g in those living in homes in the lowest tertile
      (P<0.05). CONCLUSIONS: Availability of fruits and vegetables in the home was
      associated with intake of those foods in a sample of African-American mothers and
      infants. Results support making changes in the home environment as a method of
      promoting changes in fruit and vegetable intake.

PMID- 21963016
TI  - A meat, processed meat, and French fries dietary pattern is associated with high
      allostatic load in Puerto Rican older adults.
AB  - BACKGROUND: Consumption of certain dietary patterns, such as a Western diet, has
      been associated with unfavorable physiologic outcomes. Diet has been proposed as
      a contributor to allostatic load, a composite measure of physiological
      dysregulation. OBJECTIVE: To determine the association of dietary patterns,
      defined by "meat and french fries," "traditional Puerto Rican foods" (rice,
      beans, and oils), or "sweets," with allostatic load, and with the 10 individual
      physiologic parameters that comprise it. PARTICIPANTS: Baseline data collected
      from participants of the Boston Puerto Rican Health Study (n=1,117; aged 45 to 75
      years) was used to run linear and logistic regression models, adjusting for age,
      sex, alcohol intake, smoking, medications, energy intake, and body mass index or
      physical activity. RESULTS: Significant trends across increasing quintiles of the
      meat and french fries pattern were observed for higher allostatic load score
      (P=0.002), waist circumference (P=0.032), systolic blood pressure (P=0.008), and
      diastolic blood pressure (P<0.0001). Participants in the highest quintile of the
      meat and french fries pattern had significantly higher allostatic load score than
      those in the lowest quintile (mean 4.3+/-0.11 vs 3.9+/-0.12, P=0.030), and had
      higher odds of having high allostatic load (odds ratio [95% confidence interval]:
      1.8 [1.2 to 2.9]), low dehydroepiandrosterone sulfate (odds ratio 1.9 [95%
      confidence interval: 1.2 to 3.1]), and high glycosylated hemoglobin (odds ratio
      1.7 (95% confidence interval: 1.0 to 2.9]). The traditional pattern was not
      associated with allostatic load, whereas a significant association between the
      sweets pattern and allostatic load disappeared after restricting analysis to
      participants without diabetes. CONCLUSIONS: A meat, processed meat, and french
      fries dietary pattern may contribute to the deregulation of multiple physiologic
      parameters in Puerto Rican adults. Efforts to limit consumption of this pattern
      may help prevent further cumulative physiological dysregulation in this high risk
      population.

PMID- 21963017
TI  - Intake of milk with added micronutrients increases the effectiveness of an energy
      restricted diet to reduce body weight: a randomized controlled clinical trial in
      Mexican women.
AB  - BACKGROUND: Micronutrient deficiencies have been associated with an increase in
      fat deposition and body weight; thus, adding them to low-fat milk may facilitate
      weight loss when accompanied by an energy-restricted diet. OBJECTIVE: The
      objective was to evaluate the effect of the intake of low-fat milk and low-fat
      milk with added micronutrients on anthropometrics, body composition, blood
      glucose levels, lipids profile, C-reactive protein, and blood pressure of women
      following an energy-restricted diet. DESIGN: A 16-week randomized, controlled
      intervention study. PARTICIPANTS/SETTINGS: One hundred thirty-nine obese women
      (aged 34+/-6 years) from five rural communities in Queretaro, Mexico.
      INTERVENTION: Women followed an energy-restricted diet (-500 kcal) and received
      in addition one of the following treatments: 250 mL of low-fat milk (LFM) three
      times/day, 250 mL of low-fat milk with micronutrients (LFM+M) three times/day, or
      a no milk control group (CON). Weight, height, and hip and waist circumferences
      were measured at baseline and every 4 weeks. Body composition measured by dual
      energy x-ray absorptiometry, blood pressure, and blood analysis were done at
      baseline and at the end of the 16 weeks. MAIN OUTCOME MEASURES: Changes in weight
      and body composition. STATISTICAL ANALYSIS: One-factor analysis of variance,
      adjusted by age, baseline values, and community random effects. RESULTS: After
      the 16-week intervention, participants in the LFM+M group lost significantly more
      weight (-5.1 kg; 95% CI: -6.2 to -4.1) compared with LFM (-3.6 kg; 95% CI: -4.7
      to -2.6) and CON (-3.2 kg; 95% CI: -4.3 to -2.2) group members (P=0.035). Body
      mass index change in the LFM+M group (-2.3; 95% CI: -2.7 to -1.8) was
      significantly greater than LFM group members (-1.5; 95% CI: -2.0 to -1.1) and CON
      group members (-1.4; 95% CI: -1.9 to -0.9) (P=0.022). Change in percent body fat
      among LFM+M group members (-2.7%; 95% CI: -3.2 to -2.1) was significantly higher
      than LFM group members (-1.8%; 95% CI: -2.3 to -1.3) and CON group members (
      1.6%; 95% CI: -2.2 to -1.0) (P=0.019). Change in bone mineral content was
      significantly higher in LFM group members (29 mg; 95% CI: 15 to 44) and LFM+M
      group members (27 mg; 95% CI: 13 to 41) compared with CON group members (-2 mg;
      95% CI: -17 to -14) (P=0.007). No differences were found between groups in
      glucose level, blood lipid profile, C-reactive protein level, or blood pressure.
      CONCLUSIONS: Intake of LFM+M increases the effectiveness of an energy-restricted
      diet to treat obesity, but had no effect on blood lipid levels, glucose levels, C
      reactive protein, or blood pressure.

PMID- 21963018
TI  - Perceptions about varieties of brown rice: a qualitative study from Southern
      India.
AB  - Consumption of whole grains, such as brown rice, compared to white rice can
      decrease the risk of type 2 diabetes mellitus. This qualitative study conducted
      in 2009 sought to identify factors that can act as barriers to or promote
      acceptance of brown rice as a staple food among South Indian adults (n=65). Using
      purposeful sampling, eight focus groups were conducted among adults with normal
      body mass index and adults who were overweight, aged 24 to 47 years, living in
      slum and non-slum sites in Chennai, a city in Southern India. These focus groups,
      conducted in Tamil, the local language of Chennai, were homogenous by sex. The
      focus groups were audiotaped after obtaining consent. Results were transcribed
      and coded according to four major themes that emerged during the focus group
      discussions, including culture and dietary practices, factors influencing rice
      preferences, awareness and perceptions of brown rice, and barriers to and factors
      influencing acceptance of brown rice. Overall, the majority of participants
      favored eating rice and rice-based foods. Tradition largely dictated the specific
      form of rice that people consumed. Awareness about the nutritive properties of
      brown rice was poor and was cited as a major barrier to its acceptance. In
      addition, participants tended to consider cooked rice that was neither white nor
      long-grained to be inferior. However, they believed that although convincing
      people to switch to brown rice would be a slow process, promoting its healthful
      benefits could serve to popularize it.

PMID- 21963019
TI  - A systematic review of behavioral interventions to promote intake of fruit and
      vegetables.
AB  - Fruit and vegetable (F/V) intake in the United States remains below recommended
      levels despite evidence of the health benefits of regular consumption. Efforts to
      increase F/V intake include behavior-based interventions. A systematic review of
      MEDLINE PubMed and PsycINFO databases (2005-2010) was conducted to identify
      behavior-based intervention trials designed to promote F/V intake. Using
      predetermined limits and selection criteria, 34 studies were identified for
      inclusion. Behavior-based interventions resulted in an average increase in F/V
      intake of +1.13 and +0.39 servings per day in adults and children, respectively.
      Interventions involving minority adults or low-income participants demonstrated
      average increases in daily F/V consumption of +0.97 servings/day, whereas
      worksite interventions averaged +0.8 servings/day. Achieving and sustaining F/V
      intake at recommended levels of intake across the population cannot be achieved
      through behavior-based interventions alone. Thus, efforts to combine these
      interventions with other approaches including social marketing, behavioral
      economics approaches, and technology-based behavior change models should be
      tested to ensure goals are met and sustained.

PMID- 21963020
TI  - Fruit consumption is associated with lower carotid intima-media thickness and C
      reactive protein levels in patients with type 2 diabetes mellitus.
AB  - Preliminary evidence in support of fruit intake for the prevention of
      cardiovascular disease in patients with type 2 diabetes mellitus (T2DM) is still
      limited. The objective of this study was to evaluate the association between
      fruit consumption and cardiovascular risk factors such as carotid intima-media
      thickness (CIMT) and high-sensitive C-reactive protein (hsCRP) in patients with
      T2DM. In this cross-sectional study, 407 patients with T2DM were recruited from
      August 2007 to December 2009. Dietary assessment based on 3-day 24-hour recall
      interviews, hsCRP levels, and CIMT were examined. Participants were categorized
      into three tertiles based on fruit intake. Comparisons of the participants'
      clinical characteristics among the three categories were performed using either
      one-way analysis of variance or analysis of covariance. In patients with type 2
      diabetes with CIMT >=1 mm, the intake of fruit was lower (P=0.001), whereas the
      serum hsCRP level was higher (P<0.001) compared with patients showing CIMT <1 mm.
      Results of the multivariable logistic regression analysis showed that the odds
      ratios of CIMT and hsCRP were 8% and 31% lower, respectively, in participants in
      the top tertile compared with those in the lowest tertile (P=0.018 and P<0.001,
      respectively) after adjustment for potential confounders. Hence, a reduction in
      hsCRP concentration and CIMT were found to be associated with an increase in
      fruit intake. Sufficient daily intake of fruits should, therefore, be considered
      as an important component of a medical nutritional therapy strategy for the
      prevention of cardiovascular diseases in patients with T2DM.

PMID- 21963021
TI  - Recall of vegetable eating affects future predicted enjoyment and choice of
      vegetables in British University undergraduate students.
AB  - Predictions about enjoyment of future experiences are influenced by recalling
      similar past experiences. However, little is known about the relationship between
      hedonic memories of past eating episodes and future eating behavior. We
      investigated recall of previous experiences of eating vegetables and the effect
      of recall on future predicted liking for and consumption of vegetables. British
      University undergraduate students were asked to retrieve memories of previous
      occasions when they ate vegetables and were asked to rate how enjoyable those
      experiences were (Study 1, n=54). The effect of different types of memory recall
      (including vegetable eating recall) and visualization of someone else eating
      vegetables (to control for priming effects) on predicted likelihood of choosing
      vegetables and predicted enjoyment of eating vegetables was examined (Study 2,
      n=95). Finally, the effect of recalling vegetable eating memories on actual food
      choice from a buffet was assessed (Study 3, n=63). It is reported that people
      recall positive memories of past vegetable consumption (P<0.05) and that
      reminding people of these experiences results in higher predicted future liking
      for vegetables (P<0.05) and choice of a larger portion size of vegetables
      (P<0.05) compared with recall of a personal nonfood memory, a nonvegetable food
      memory, or visualization of someone else enjoying eating vegetables (increase of
      approximately 70% in vegetable portion size compared to controls). The results
      suggest that recall of previous eating experiences could be a potential strategy
      for altering food choices.

PMID- 21963022
TI  - Increasing access and affordability of produce improves perceived consumption of
      vegetables in low-income seniors.
AB  - High cost and limited access to food have been associated with lower intake of
      fruits and vegetables in limited-income individuals. The Veggie Mobile is a van
      that carries fresh produce and travels in low-income neighborhoods, selling
      fruits and vegetables at a fraction of regular supermarket prices. The purpose of
      this study was to determine whether participation in the Veggie Mobile increases
      fruit and vegetable intake in a group of seniors. The intervention, buying fruits
      and vegetables from the Veggie Mobile, was implemented between April and October
      2008 in two senior housing sites that had not previously received Veggie Mobile
      services. Participants were asked about fruit and vegetable intake using a
      modified six-item questionnaire based on the Behavioral Risk Factor Surveillance
      System at preintervention and again at 3 to 5 months. The post-survey also
      included questions about perceived benefits and barriers to using the Veggie
      Mobile. The two cross-sections of seniors were matched using date of birth.
      Wilcoxon signed rank test and paired samples t tests examined change in pre- and
      post-intervention variables. Seventy-nine older adults completed the baseline
      survey and 63 completed the post-survey. Of these, 43 participants completed both
      surveys (70% white [n=30], mean age 69 +/- 9 years). Mean intake of fruits and
      vegetables after using the Veggie Mobile increased by 0.37 servings/day.
      Vegetable intake alone increased from 1.98 +/- 1.71 servings/day to 2.58 +/- 1.4
      servings/day (P=0.027), half of which was potatoes. Change in fruit intake was
      not significant (P=0.358). At post-intervention, seniors visited the supermarket
      less often (P=0.001) and spent an average of $14.92 less during their last visit.
      The majority of participants who completed the post-survey (62 of 63) indicated
      being satisfied with the program. The Veggie Mobile provides an example of a
      simple community intervention that has potential to lead to positive behavior
      change among low-income seniors.

PMID- 21963023
TI  - Contribution of take-out food consumption to socioeconomic differences in fruit
      and vegetable intake: a mediation analysis.
AB  - Lower fruit and vegetable (F/V) intake among socioeconomically disadvantaged
      groups has been well documented, and may be a consequence of a higher consumption
      of take-out foods. This study examined whether, and to what extent, take-out food
      consumption mediated (explained) the association between socioeconomic position
      and F/V intake. A cross-sectional postal survey was conducted among 1,500
      randomly selected adults aged 25 to 64 years in Brisbane, Australia, during 2009
      (response rate 63.7%, N=903). A food frequency questionnaire assessed usual daily
      servings of F/V (0 to 6), overall take-out consumption (times per week), and the
      consumption of 22 specific take-out items (never to once per day or more). These
      specific take-out items were grouped into "less healthy" and "healthy" choices
      and indexes were created for each type of choice (0 to 100). Socioeconomic
      position was ascertained by education. The analyses were performed using linear
      regression, and a bootstrap resampling approach estimated the statistical
      significance of the mediated effects. Mean daily servings of F/V were 1.89+/-1.05
      and 2.47+/-1.12, respectively. The least educated group members were more likely
      to consume fewer servings of fruit (beta= -.39, P<0.001) and vegetables (beta= 
      .43, P<0.001) compared with members of the highest educated group. The
      consumption of "less healthy" take-out food partly explained (mediated) education
      differences in F/V intake; however, no mediating effects were observed for
      overall and "healthy" take-out consumption. Regular consumption of "less healthy"
      take-out items may contribute to socioeconomic differences in F/V intake,
      possibly by displacing these foods.

PMID- 21963024
TI  - Differences in diet pattern adherence by nativity and duration of US residence in
      the Mexican-American population.
AB  - Literature on the diet of the Mexican-American population suggests that food
      consumption differs by nativity and duration of residence in the United States.
      However, no studies have used dietary pattern analysis to investigate these
      differences. To create dietary patterns, we used principal components analysis on
      food frequency questionnaire data for all adult respondents of the National
      Health and Nutrition Examination Survey years 2003-2006. Four dietary patterns
      were identified: Western, Healthy, Tomato/Tortilla, and Coffee/Sugar. Least
      squares means regression was used to test differences in adjusted mean dietary
      adherence scores among Mexico-born Mexican-American adults residing in the United
      States for <15 years (n=302), Mexico-born Mexican-American adults residing in the
      United States for >=15 years (n=234), US-born Mexican-American adults (n=509),
      and US-born non-Hispanic whites (n=2,530) aged 18 to 69 years. Mean score for
      each diet pattern did not differ significantly by duration of US residence
      category in the Mexico-born Mexican-American population. However, in comparison
      to all Mexico-born Mexican Americans, US-born Mexican Americans had significantly
      lower score for the Tomato/Tortilla pattern, and significantly higher score for
      the Western pattern. Scores for the Healthy pattern were relatively low in all
      Mexican-American subgroups, indicating low adherence to the Healthy diet.
      However, Healthy diet scores of Mexico-born Mexican Americans among those aged
      <=41 years appeared more similar to those of US-born non-Hispanic whites than US
      born Mexican Americans. Education and policy action promoting healthy food access
      in Hispanic neighborhoods could help limit consumption of Western and
      Coffee/Sugar diet patterns and promote healthier choices in the Mexican-American
      population.

PMID- 21963025
TI  - Development of the behaviorally focused fruits & Veggies--More Matters public
      health initiative.
AB  - Due to changing recommendations for fruit and vegetable (F/V) intake, public
      health and private organizations recognized the need to revise communications and
      programs that promote F/V consumption. This article describes formative research
      conducted in 2005 to develop a new identity for the 5 A Day Program, updated to
      the Fruits & Veggies--More Matters program. The objective was to re-brand the 5 A
      Day Program's campaign message to be adaptable, sustainable, and compelling,
      while leveraging the program's existing message dissemination infrastructure.
      Formative research included interviews with representatives from government,
      nonprofit organizations, and industry, and consumer perspectives from interviews,
      focus groups, and an online survey. Public health and private organizations
      agreed that a compelling emotional benefit was needed to motivate consumers to
      eat more F/V and that messaging needed to be used consistently among national,
      state, and local programs. Interviews and focus groups targeted mothers who
      believed they and their families were getting enough F/V, knew they could eat
      more, but needed to be convinced why they should do so. The most effective
      messages appealed to mothers' emotional needs to be responsible, leveraged
      functional intrinsic values of F/V, did not try to quantify "enough," and focused
      on small steps. When the Fruits & Veggies-More Matters slogan and graphic were
      viewed together, the majority (62%) said it increased their interest in eating
      more F/V. The Fruits & Veggies-More Matters brand offers numerous opportunities
      for promoting F/V consumption through this public health initiative.

PMID- 21963026
TI  - Computerized portion-size estimation compared to multiple 24-hour dietary recalls
      for measurement of fat, fruit, and vegetable intake in overweight adults.
AB  - Validated self-report methods of dietary assessment exist and might be improved
      in terms of both accuracy and cost-efficiency with computer technology. The
      objectives of this preliminary study were to develop an initial version of an
      interactive CD-ROM program to estimate fruit, vegetable, and fat intake, and to
      compare it to multiple 24-hour dietary recalls (averaged over 3 days). In 2009,
      overweight male and female adults (n=205) from Lane County, OR, completed
      computerized and paper versions of fruit, vegetable, and fat screening
      instruments, and multiple 24-hour dietary recalls. Summary scores from the 10
      item National Cancer Institute Fruit and Vegetable Scan and the 18-item Block Fat
      Screener were compared to multiple 24-hour dietary recall-derived fruit/vegetable
      and fat intake estimates (criterion measures). Measurement models were used to
      derive deattenuated correlations with multiple 24-hour dietary recalls of paper
      and CD-ROM administrations of Fruit and Vegetable Scan fruit intake, vegetable
      intake, and fruit and vegetable intake, and Block Fat Screener fat intake. The
      computerized assessment and paper surveys were related to multiple 24-hour
      dietary recall-derived fruit/vegetable and fat intake. Deattenuated correlation
      coefficients ranged from 0.50 to 0.73 (all P<=0.0001). The CD-ROM-derived
      estimate of fruit intake was more closely associated with 24-hour dietary recall
      (r=0.73) than the paper-derived estimate (r=0.54; P<0.05), but the other
      comparisons did not differ significantly. Findings from this preliminary study
      with overweight adults indicate the need for additional enhancements to the CD
      ROM assessment and more extensive validation studies.

PMID- 21963027
TI  - 2011 future connections summit on dietetics practice, credentialing, and
      education: the summit at a glance.

PMID- 21963028
TI  - 2011 future connections summit on dietetics practice, credentialing, and
      education: summary of presentations on shaping the future of the dietetics
      profession.

PMID- 21963029
TI  - Where can I find reliable consumer nutrition information?

PMID- 21963030
TI  - The "volumetric" pulsatility index as evaluated by spatiotemporal imaging
      correlation (STIC): a preliminary description of a novel technique, its
      application to the endometrium and an evaluation of its reproducibility.
AB  - We propose new volumetric indices derived from three-dimensional (3-D) power
      Doppler (PD) using spatiotemporal imaging correlation (STIC) to overcome the
      influence of machine settings and attenuation. In this study, we describe these
      indices and evaluate their interobserver reliability: two static-3-D and two STIC
      PD datasets were acquired from 60 women and two observers (blinded analysis)
      evaluated vascularization index (VI), the flow index (FI) and the vascularization
      flow index (VFI) of standardized spherical samples of endometrium. Three new
      indices were determined based on maximum, minimum and mean values (vPI, vRI(max
      min), vS/D(max-min)) and two indices from frames subjectively defined as systole
      and diastole (vRI(sys-dia), vS/D(sys-dia)). Highest intraclass coefficient
      correlations (ICCs) were obtained from vPI derived from VI or VFI (0.77-0.76),
      followed by vRI(max-min) (0.72-0.72) and vS/D(max-min) (0.52-0.49). ICCs from
      indices based on subjectively systole and diastole or FI were consistently lower
      (<0.40). We conclude that the subjective choice of systolic and diastolic frames
      only lacks reliability but indices based on complete evaluation may reliably be
      used.

PMID- 21963031
TI  - Experimental investigation of the effect of stiffness, exposure time and scan
      direction on the dimension of ultrasound histotripsy lesions.
AB  - Histotripsy uses high-intensity focused ultrasound to create energetic bubble
      clouds inside tissue to liquefy a region and has the advantages of higher
      contrast B-mode monitoring and sharp borders. This study experimentally
      investigated the effects of stiffness, exposure time and scan direction on the
      size of histotripsy-induced lesions in agar samples. A targeted region 0.45 cm
      wide (lateral) and 0.6 cm deep (axial) was scanned with the step sizes of 0.075
      cm and 0.3 cm, respectively. The single-element spherically focused source (1.1
      MHz, 6.34 cm focal length, f/1) had the peak compressional and rarefactional
      pressures of approximately 102 and 17 MPa. Pulses consisted of 20-cycle sine wave
      tone bursts with a burst period of 3 ms and exposure time of 15, 30 or 60 s.
      Also, both inward and outward scan direction were tested along the beam axis. The
      liquefied lesions generally had a larger size than the initially targeted region
      with larger sizes corresponding to softer agar and longer exposure. There was not
      a statistically significant difference in the lesion size with scan direction.

PMID- 21963032
TI  - In vivo gene transfer into the ocular ciliary muscle mediated by ultrasound and
      microbubbles.
AB  - This study aimed to assess application of ultrasound (US) combined with
      microbubbles (MB) to transfect the ciliary muscle of rat eyes. Reporter DNA
      plasmids encoding for Gaussia luciferase, beta-galactosidase or the green
      fluorescent protein (GFP), alone or mixed with 50% Artison MB, were injected into
      the ciliary muscle, with or without US exposure (US set at 1 MHz, 2 W/cm(2), 50%
      duty cycle for 2 min). Luciferase activity was measured in ocular fluids at 7 and
      30 days after sonoporation. At 1 week, the US+MB treatment showed a significant
      increase in luminescence compared with control eyes, injected with plasmid only,
      with or without MB (*2.6), and, reporter proteins were localized in the ciliary
      muscle by histochemical analysis. At 1 month, a significant decrease in
      luciferase activity was observed in all groups. A rise in lens and ciliary muscle
      temperature was measured during the procedure but did not result in any
      observable or microscopic damages at 1 and 8 days. The feasibility to transfer
      gene into the ciliary muscle by US and MB suggests that sonoporation may allow
      intraocular production of proteins for the treatment of inflammatory, angiogenic
      and/or degenerative retinal diseases.

PMID- 21963033
TI  - Impact of nonlinear distortion on acoustic radiation force elastography.
AB  - High-intensity focused ultrasound (HIFU) produces an acoustic radiation force
      that induces tissue displacement, which can be measured by monitoring time shifts
      in the backscattered signals from interrogation pulses. If the pulse occurs
      simultaneously with the HIFU, the arrival time of the backscatter will be biased
      because nonlinearity associated with the HIFU changes the local sound speed.
      Measurements of the pressure field using 1.1 MHz HIFU and a 7.5 MHz pulse in
      water exhibited a nonlinearly induced apparent displacement (NIAD) that varied
      with the HIFU pressure, propagation distance and the timing of the pulse relative
      to the HIFU. Nonlinear simulations employing the KZK equation predicted NIADs
      that agreed with measurements. Experiments with chicken breast demonstrated a
      NIAD with magnitude similar to that expected from the radiation force. Finally it
      was shown that if two pulses were fired with different phases relative to the
      HIFU, then upon averaging, the NIAD could be mitigated.

PMID- 21963034
TI  - Is low-intensity pulsed ultrasound effective for revitalizing a severely necrotic
      small bone? An experimental rabbit model.
AB  - Previously, we successfully applied a new method composed of drilling, bone
      marrow transplantation (BMT), external fixation and low-intensity pulsed
      ultrasound (LIPUS) for the clinical treatment of Kienbock's disease. The purpose
      of this study was to investigate whether bone regeneration can be induced by
      LIPUS and/or multiple drilling and/or BMT within a severely necrotic small-bone
      rabbit model. Eighteen rabbits were divided into three groups (BMT, drilling and
      control) and LIPUS stimulation was introduced daily for 8 weeks post
      transplantation. Next, 12 additional rabbits were produced for the BMT group and
      LIPUS stimulation was introduced daily for 4 and 12 weeks (n = 6 for each).
      Histopathologically, new bone formations were rarely observed in the drilling and
      control groups. In the BMT group, the mineralizing surface areas of LIPUS(+)
      showed a significant increase compared with LIPUS(-) for 8 weeks. LIPUS treatment
      alone did not accelerate the revitalization of necrotic bones. However, LIPUS
      combined with BMT tended to promote new bone formation.

PMID- 21963035
TI  - The feasibility of low mechanical index contrast enhanced ultrasound (CEUS) in
      distinguishing malignant from benign thoracic lesions.
AB  - We proposed to assess the feasibility of low mechanical index (MI) contrast
      enhanced ultrasound (CEUS) in the characterisation of thoracic lesions. Fifty
      patients were prospectively examined by CEUS and images acquired on a low MI
      (0.17-0.24) setting following injection of SonoVue. From region-of-interest (ROI)
      generated signal intensity (SI) time curves, the maximum SI, bolus arrival time
      (BAT), time to peak intensity (TTP), wash-in slope and mean transit time (MTT)
      were calculated. Using the Wilcoxon rank test; parameters and threshold values
      for positive differentiation were determined. In addition, for the parameters
      that allowed positive differentiation between malignant and benign lesions
      receiver operator curves (ROC) were obtained. The wash-in slope, TTP and MTT (p =
      0.0003, <0.0001, 0.02) allowed positive differentiation. The sensitivity and
      specificity was 93% and 78%, with 6.87 s(-1) threshold value for the wash-in
      slope, 78% and 89% with 11.84 s threshold for the TTP and 48% and 89% with 78.6 s
      threshold for the MTT. CEUS is a useful tool for differentiating malignant and
      benign thoracic lesions.

PMID- 21963036
TI  - Precision manufacture of phase-change perfluorocarbon droplets using
      microfluidics.
AB  - Liquid perfluorocarbon droplets have been of interest in the medical acoustics
      community for use as acoustically activated particles for tissue occlusion,
      imaging and therapeutics. To date, methods to produce liquid perfluorocarbon
      droplets typically result in a polydisperse size distribution. Because the
      threshold of acoustic activation is a function of diameter, there would be
      benefit from a monodisperse population to preserve uniformity in acoustic
      activation parameters. Through use of a microfluidic device with flow-focusing
      technology, the production of droplets of perfluoropentane with a uniform size
      distribution is demonstrated. Stability studies indicate that these droplets are
      stable in storage for at least two weeks. Acoustic studies illustrate the
      thresholds of vaporization as a function of droplet diameter, and a logarithmic
      relationship is observed between acoustic pressure and vaporization threshold
      within the size ranges studied. Droplets of uniform size have very little
      variability in acoustic vaporization threshold. Results indicate that
      microfluidic technology can enable greater manufacturing control of phase-change
      perfluorocarbons for acoustic droplet vaporization applications.

PMID- 21963037
TI  - Cavitation-enhanced extravasation for drug delivery.
AB  - A flow-through tissue-mimicking phantom composed of a biocompatible hydro-gel
      with embedded tumour cells was used to assess and optimize the role of ultrasound
      induced cavitation on the extravasation of a macromolecular compound from a
      channel mimicking vessel in the gel, namely a non-replicating luciferase
      expressing adenovirus (Ad-Luc). Using a 500 KHz therapeutic ultrasound transducer
      confocally aligned with a focussed passive cavitation detector, different
      exposure conditions and burst mode timings were selected by performing time and
      frequency domain analysis of passively recorded acoustic emissions, in the
      absence and in the presence of ultrasound contrast agents acting as cavitation
      nuclei. In the presence of Sonovue, maximum ultraharmonic emissions were detected
      for peak rarefactional pressures of 360 kPa, and maximum broadband emissions
      occurred at 1250 kPa. The energy of the recorded acoustic emissions was used to
      optimise the pulse repetition frequency and duty cycle in order to maximize
      either ultraharmonic or broadband emissions while keeping the acoustic energy
      delivered to the focus constant. Cell viability measurements indicated that none
      of the insonation conditions investigated induces cell death in the absence of a
      therapeutic agent (i.e. virus). Phase contrast images of the tissue-mimicking
      phantom showed that short range vessel disruption can occur when ultra-harmonic
      emissions (nf0/2) are maximised whereas formation of a micro-channel
      perpendicular to the flow can be obtained in the presence of broadband acoustic
      emissions. Following Ad-Luc delivery, luciferase expression measurements showed
      that a 60-fold increase in its bioavailability can be achieved when broadband
      noise emissions are present during insonation, even for modest contrast agent
      concentrations. The findings of the present study suggest that drug delivery
      systems based on acoustic cavitation may help enhance the extravasation of
      anticancer agents, thus increasing their penetration distance to hypoxic regions
      and poorly vascularised tumour regions.

PMID- 21963038
TI  - Simultaneous backscatter and attenuation estimation using a least squares method
      with constraints.
AB  - Backscatter and attenuation variations are essential contrast mechanisms in
      ultrasound B-mode imaging. Emerging quantitative ultrasound methods extract and
      display absolute values of these tissue properties. However, in clinical
      applications, backscatter and attenuation parameters sometimes are not easily
      measured because of tissues inhomogeneities above the region-of-interest (ROI).
      We describe a least squares method (LSM) that fits the echo signal power spectra
      from a ROI to a three-parameter tissue model that simultaneously yields estimates
      of attenuation losses and backscatter coefficients. To test the method, tissue
      mimicking phantoms with backscatter and attenuation contrast as well as uniform
      phantoms were scanned with linear array transducers on a Siemens S2000.
      Attenuation and backscatter coefficients estimated by the LSM were compared with
      those derived using a reference phantom method (Yao et al. 1990). Results show
      that the LSM yields effective attenuation coefficients for uniform phantoms
      comparable to values derived using the reference phantom method. For layered
      phantoms exhibiting nonuniform backscatter, the LSM resulted in smaller
      attenuation estimation errors than the reference phantom method. Backscatter
      coefficients derived using the LSM were in excellent agreement with values
      obtained from laboratory measurements on test samples and with theory. The LSM is
      more immune to depth-dependent backscatter changes than commonly used reference
      phantom methods.

PMID- 21963039
TI  - Properties of ultrasonic waves in bovine bone marrow.
AB  - We investigated the properties of ultrasonic waves in bovine bone marrow. Six
      bone marrow samples were obtained from different parts (proximal, middle and
      distal) of the shafts of two bovine femora without destruction. The measured
      frequency range was 3 to 10 MHz, and the temperature range was 15 to 40 degrees
      C. Both wave velocity and attenuation coefficient in bone marrow always decreased
      as temperature increased. The velocity ranged from 1400 to 1610 m/s and
      attenuation coefficient ranged from 4 to 16 dB/cm. Wave velocities in bone marrow
      were similar to those in water, whereas the temperature dependences were
      different, and the wave attenuation coefficients were much higher than those in
      water. The dependence of velocity on temperature changed slightly around 23-24
      degrees C, where a transition from soft gel to oily liquid occurred. The
      transition temperature was confirmed by differential scanning calorimetry (DSC).
      Below this transition temperature, positive velocity dispersion was observed.

PMID- 21963040
TI  - The anti-tumour effect of cisplatin and ifosfamide on xenografted squamous cell
      carcinoma of the head and neck is schedule-dependent.
AB  - The role of chemotherapy (CHX) in squamous cell carcinoma of the head and neck
      (SCCHN) has been expanding. Although combination chemotherapy regimens regularly
      produce significantly high response rates, meta-analyses show little benefit
      regarding final outcome. One way to improve induction CHX is to improve drug
      combinations and schedules for CHX. Cisplatin (CDDP) is one of the most active
      drugs in the treatment of patients with SCCHN, and it is used in most
      combinations. Ifosfamide (IFO) is another agent that has shown activity in the
      treatment of patients with SCCHN. A poorly differentiated squamous cell carcinoma
      xenografted to nude mice was used. CDDP (2.5 mg/kg) and IFO (100 mg/kg) as single
      bolus doses induced significant retardation of tumour growth. Single drug
      administration was compared with CDDP given before IFO and IFO given before CDDP.
      Mean specific growth delay (SGD) for untreated controls was 0. For CDDP as single
      drug it was 1.50, for IFO as single drug it was 0.79, for CDDP given 4 h before
      IFO it was 1.79, and for IFO given 4 h before CDDP it was 2.90. Maximum toxicity,
      calculated as change in median weight at day 7, was less than 10%. The efficacy
      and toxicity of CDDP and IFO is schedule-dependent, with IFO given before CDDP
      being more effective than CDDP given before IFO. This is in contrast to most
      schedules used clinically. The toxicities were comparable. The number of
      combinations of drugs with respect to order and time interval is of a magnitude
      that would not be possible to test clinically. In the pursuit of more efficient
      combinations, the importance of order and schedule of drugs and also the
      potential of xenografted SSCHN are underestimated.

PMID- 21963041
TI  - Mercury inhibits the L170C mutant of aquaporin Z by making waters clog the water
      channel.
AB  - We conduct in silico experiments of the L170C mutant of the Escherichia coli
      aquaporin Z (AQPZ) with and without mercury bonded to residue Cys 170. We find
      that bonding mercury to Cys 170 does not induce consequential structural changes
      to the protein. We further find that mercury does not stick in the middle of the
      water channel to simply occlude water permeation, but resides on the wall of the
      water pore. However, we observe that the water permeation coefficient of L170C
      Hg(+) (with one mercury ion bonded to Cys 170) is approximately half of that of
      the mercury-free L170C. We examine the interactions between the mercury ion and
      the waters in its vicinity and find that five to six waters are strongly
      attracted by the mercury ion, occluding the space of the water channel. Therefore
      we conclude that mercury, at low concentration, inhibits AQPZ-L170C mutant by
      making water molecules clog the water channel.

PMID- 21963042
TI  - Validation of a therapeutic scheme for the treatment of resistant hypertension.
AB  - We tested the hypothesis that a therapeutic strategy of substituting the diuretic
      (most commonly hydrochlorothiazide) with chlorthalidone (50 mg/day), and, if
      needed, the calcium channel blocker with the highest dose of the most commonly
      used calcium antagonist (amlodipine 10 mg), and adding on top a direct renin
      inhibitor (aliskiren 300 mg) is effective to treat resistant hypertensive
      patients not responding to spironolactone. The scheme was tested in a group of 76
      patients who had true treatment resistant hypertension (24-hour mean blood
      pressure >=130/80 mm Hg while receiving three or more drugs). An effective
      response to spironolactone was defined as 24-hour ambulatory systolic blood
      pressure (SBP) drop by more than 20 mm Hg, and was obtained with 25-50 mg in 60
      patients (78.9%). In patients with inadequate response to spironolactone (n =
      16), we administered the triple combination plus the remaining therapy, a mean
      decrease of 29 mm Hg (95% CI 11-48; P = .004) for SBP and 12 mm Hg (95% CI: 4-20
      mm Hg) for diastolic BP were observed. In only 1 of 16 patients (6%), the
      response was considered as insufficient. These data indicate the need for further
      testing this scheme that looks really promising to treat resistant hypertensive
      patients not responding to spironolactone.

PMID- 21963043
TI  - Preliminary results of a new small-bore percutaneous pleural catheter used for
      treatment of malignant pleural effusions in ECOG PS 3-4 patients.
AB  - BACKGROUND: In cancer patients with malignant pleural effusions(MPEs),the
      commonest procedure to treat them with palliative intention is talc pleurodesis
      (TP) which can be obtained with talc slurry (TS) using small-bore
      catheters(SBC)or with thoracoscopic poudrage. SBC use is therefore rapidly
      increasing. The aim of this paper is to present our preliminary TP results using
      a new percutaneous chest drainage system(UNICO(r), Redax, Mirandola Modena,
      Italy). METHODS: In the period 1st March-20th of July 2011,seven consecutive ECOG
      PS 3-4 patients(4 females, mean age 73.2 +/- 12.1 years),unfit for thoracoscopic
      talc poudrage, were enrolled in our study. All patients received many
      thoracentesis before the placement of a chest drainage(median thoracentesis
      number:4.42 +/- 1.13).UNICO(r) was bedside placed in all cases and TS was
      administered through the drainage when the overall fluid amount didn't exceed 150
      200 ml/24 h and the lung was correctly re-expanded at the chest X-ray control.
      RESULTS: There were no clinical complications following the placement of the
      drainage: its placement was easy, safe and well-tolerated by all patients. The
      median chest tube stay, before TS, was 7.2 +/- 2.7 days while the median chest
      tube stay after TS was 1.5 +/- 0.7 days. A satisfactory radiological lung
      expansion was achieved in all cases; PL effectiveness and dyspnea relief were
      complete in 6 and 4 cases, respectively. No patients required any further
      thoracentesis. CONCLUSIONS: TS through UNICO(r) is safe and efficient. The
      drainage was well-tolerated by all patients, even in case of its long-term stay.
      We may conclude that bedside TS through this new small-bore percutaneous drainage
      should be proposed as a viable clinical solution for MPEs in ECOG PS 3-4
      patients, unfit for a thoracoscopic procedure. Moreover, with this device, we
      believe that TS might be an accessible procedure for pulmonologists and
      oncologists too.

PMID- 21963044
TI  - Characterization, leachability and valorization through combustion of residual
      chars from gasification of coals with pine.
AB  - This paper presents the study of the combustion of char residues produced during
      co-gasification of coal with pine with the aim of characterizing them for their
      potential use for energy. These residues are generally rich in carbon with the
      presence of other elements, with particular concern for heavy metals and
      pollutant precursors, depending on the original fuel used. The evaluation of
      environmental toxicity of the char residues was performed through application of
      different leaching tests (EN12457-2, US EPA-1311 TCLP and EA NEN 7371:2004). The
      results showed that the residues present quite low toxicity for some of
      pollutants. However, depending on the fuel used, possible presence of other
      pollutants may bring environmental risks. The utilization of these char residues
      for energy was in this study evaluated, by burning them as a first step pre
      treatment prior to landfilling. The thermo-gravimetric analysis and ash
      fusibility studies revealed an adequate thermochemical behavior, without
      presenting any major operational risks. Fluidized bed combustion was applied to
      char residues. Above 700 degrees C, very high carbon conversion ratios were
      obtained and it seemed that the thermal oxidation of char residues was easier
      than that of the coals. It was found that the char tendency for releasing SO(2)
      during its oxidation was lower than for the parent coal, while for NO(X)
      emissions, the trend was observed to increase NO(X) formation. However, for both
      pollutants the same control techniques might be applied during char combustion,
      as for coal. Furthermore, the leachability of ashes resulting from the combustion
      of char residues appeared to be lower than those produced from direct coal
      combustion.

PMID- 21963046
TI  - Perinodular CK19 loss in hepatocarcinogenesis.
AB  - Cirrhotic nodules containing hepatocytes are surrounded by perinodular stroma,
      that consists of an expanded fibrous matrix and epithelial cells with ductular
      phenotype, the "ductular-reaction". Stromal invasion is a key histopathologic
      feature used to differentiate premalignant dysplastic nodules from malignant
      hepatocellular carcinoma (HCC). K19 immunoreactivity in the stromal compartment
      in cirrhotic explants was examined. Quantitative differences were manifested in
      three distinct histologically identifiable patterns: "complex" around cirrhotic
      nodules, "attenuated" around dysplastic nodules, and "absent" around HCC. These
      findings suggest marked alterations in cellular identity as an underlying
      mechanism for the reproducible extralesional K19 pattern that parallels
      progressive stages of intranodular hepatocarcinogenesis. Paracrine signalling is
      proposed as a link that emphasizes the importance of the epithelial-stromal
      compartment in malignant progression of HCC in cirrhosis.

PMID- 21963045
TI  - Gallbladder volume and ejection fraction in patients with Behcet's disease.

PMID- 21963047
TI  - The descriptions of new microanatomical structures of the male reproductive
      system and sperm of Myschocyttarus cassununga (Hymenoptera: Vespidae).
AB  - The male reproductive system of Mischocyttarus cassununga consists of two testes,
      each one with three follicles, as occurs in most Vespidae. The seminal vesicle is
      divided in two chambers, separated by a constriction, so that the anterior locus
      is a little larger. In the testicular follicles, the spermatozoa are organized in
      cysts, with approximately 128 per cyst, where the nuclei are oriented toward the
      follicle center. The spermatozoa of M. cassununga is about 97 MUm in length,
      which makes them the shortest sperm described for Vespidae. Sperm ultrastructure
      of M. cassununga is very similar of the others Vespidae. But, despite these
      similarities, the bilobated mitochondrial derivative represents an autapomorphy
      for M. cassununga. The subdivision of the seminal vesicle has never been observed
      in any other Vespidae. Thus, this study supports the validity of insect sperm
      morphology as a tool for phylogenetic analysis within Hymenoptera.

PMID- 21963048
TI  - Microstructure characterization of Al matrix composite reinforced with Ti-6Al-4V
      meshes after compression by scanning electron microscope and transmission
      electron microscope.
AB  - Compressive properties of Al matrix composite reinforced with Ti-6Al-4V meshes
      (TC4(m)/5A06 Al composite) under the strain rates of 10(-3)S(-1) and 1S(-1) at
      different temperature were measured and microstructure of composites after
      compression was characterized by scanning electron microscope (SEM) and
      transmission electron microscope (TEM). Compressive strength decreased with the
      test temperature increased and the strain-rate sensitivity (R) of composite
      increased with the increasing temperature. SEM observations showed that grains of
      Al matrix were elongated severely along 45 degrees  direction (angle between axis
      direction and fracture surface) and TC4 fibres were sheared into several parts in
      composite compressed under the strain rate of 10(-3)S(-1) at 25 degrees C and 250
      degrees C. Besides, amounts of cracks were produced at the interfacial layer
      between TC4 fibre and Al matrix and in (Fe, Mn)Al(6) phases. With the compressive
      temperature increasing to 400 degrees C, there was no damage at the interfacial
      layer between TC4 fibre and Al matrix and in (Fe, Mn)Al(6) phases, while equiaxed
      recrystal grains with sizes about 10 MUm at the original grain boundaries of Al
      matrix were observed. However, interface separation of TC4 fibres and Al matrix
      occurred in composite compressed under the strain rate of 1S(-1) at 250 degrees C
      and 400 degrees C. With the compressive temperature increasing from 25 degrees C
      to 100 degrees C under the strain rate of 10(-3) S(-1), TEM microstructure in Al
      matrix exhibited high density dislocations and slipping bands (25 degrees C),
      polygonized dislocations and dynamic recovery (100 degrees C), equiaxed
      recrystals with sizes below 500 MUm (250 degrees C) and growth of equiaxed
      recrystals (400 degrees C), respectively.

PMID- 21963049
TI  - Adenosine kinase deficiency disrupts the methionine cycle and causes
      hypermethioninemia, encephalopathy, and abnormal liver function.
AB  - Four inborn errors of metabolism (IEMs) are known to cause hypermethioninemia by
      directly interfering with the methionine cycle. Hypermethioninemia is
      occasionally discovered incidentally, but it is often disregarded as an
      unspecific finding, particularly if liver disease is involved. In many
      individuals the hypermethioninemia resolves without further deterioration, but it
      can also represent an early sign of a severe, progressive neurodevelopmental
      disorder. Further investigation of unclear hypermethioninemia is therefore
      important. We studied two siblings affected by severe developmental delay and
      liver dysfunction. Biochemical analysis revealed increased plasma levels of
      methionine, S-adenosylmethionine (AdoMet), and S-adenosylhomocysteine (AdoHcy)
      but normal or mildly elevated homocysteine (Hcy) levels, indicating a block in
      the methionine cycle. We excluded S-adenosylhomocysteine hydrolase (SAHH)
      deficiency, which causes a similar biochemical phenotype, by using genetic and
      biochemical techniques and hypothesized that there was a functional block in the
      SAHH enzyme as a result of a recessive mutation in a different gene. Using exome
      sequencing, we identified a homozygous c.902C>A (p.Ala301Glu) missense mutation
      in the adenosine kinase gene (ADK), the function of which fits perfectly with
      this hypothesis. Increased urinary adenosine excretion confirmed ADK deficiency
      in the siblings. Four additional individuals from two unrelated families with a
      similar presentation were identified and shown to have a homozygous c.653A>C
      (p.Asp218Ala) and c.38G>A (p.Gly13Glu) mutation, respectively, in the same gene.
      All three missense mutations were deleterious, as shown by activity measurements
      on recombinant enzymes. ADK deficiency is a previously undescribed, severe IEM
      shedding light on a functional link between the methionine cycle and adenosine
      metabolism.

PMID- 21963050
TI  - The uncertain relationship between obesity and prostate cancer: an Italian biopsy
      cohort analysis.
AB  - BACKGROUND: The study aims to investigate the relationship between obesity and
      prostate cancer diagnosis at biopsy. METHODS: From 2005 onwards, a consecutive
      series of patients undergoing 12-core prostate biopsy for PSA value >= 4 ng/ml
      and/or positive digital rectal examination (DRE) were enrolled. Before the
      biopsy, patients underwent a physical examination, including height and weight
      measurement. Obesity was defined as body mass index (BMI) >=30 kg/m(2). Blood
      samples were drawn from all patients and analyzed for total PSA and testosterone.
      RESULTS: 885 patients were enrolled with a median age and PSA of 67 years (range
      37-95) and 6.4 ng/ml (range 1-30) respectively. Median BMI was 27.1 kg/m(2)
      (range 18-46.6) with 185 patients classified as obese. 363 patients had cancer at
      biopsy; 76 were obese. PSA was independently associated with a higher risk of
      cancer (OR 1.09 per 1 unit PSA, p = 0.01). On multivariate analysis, the BMI was
      not significantly associated with an increased prostate cancer risk (p = 0.19).
      Out of 363 patients with prostate cancer, 154 had a Gleason score 6 (23 were
      obese) and 209 a Gleason score >=7 (53 were obese). Among men with cancer, a
      higher BMI on univariate (p = 0.001) and multivariate analysis (p = 0.005) was
      associated with high-grade disease (Gleason >= 7). CONCLUSIONS: In our single
      center study and less aggressively screened cohort, obesity is associated with an
      increased risk of a high-grade Gleason score when prostate cancer is diagnosed at
      biopsy.

PMID- 21963051
TI  - [Nephroscopy with carbon dioxide in combination with laparoscopy in the treatment
      of urinary stones].
AB  - OBJECTIVE: Laparoscopy in combination with nephroscopy is rarely used for the
      treatment of complex urinary stones or anatomical abnormalities with difficult
      access stones. During the nephroscopy, in an opened renal pelvis, large amounts
      of fluid leaks and collects in the peritoneal cavity and can be a drawback. In
      these cases, the nephroscopy with use of carbon dioxide (CO2) can be an
      alternative. We present our experience in with this technique. MATERIAL AND
      METHOD: We performed surgeries using the 3-port transperitoneal technique. Five
      patients with urolithiasis were included. Three patients had concomitant
      ureteropelvic junction stenosis, one with stones in ectopic kidney, and the third
      had a large stone impacted in the proximal ureter. Patients were treated by
      pyelolithotomy or ureterolithotomy combined with flexible nephroscopy using CO2
      and dismembered pyeloplasty was performed in appropriate cases. A flexible
      cystoscope was passed through a port and guided laparascopically through the
      opening in the renal pelvis. The gas cannula was connected to the irrigation
      channel of the endoscope to insufflate CO2 and calculi were extracted with a
      nitinol basket. RESULTS: Median age was 45 years (24-58). Mean operative time of
      nephroscopy was 22.4 minutes (range 15-48). Mean intra-operative blood loss was
      inestimable. There were no complications or conversion. Residual lithiasis
      requiring ureteroscopy was present in one patient. CONCLUSIONS: Flexible
      nephroscopy using CO2 in combination with laparoscopy is a feasible and effective
      technique for the treatment of urinary stones in selected cases to avoid
      accumulation of fluid in the peritoneal cavity.

PMID- 21963052
TI  - [Are we overtreating low risk prostate cancer?].

PMID- 21963053
TI  - Nocturia and quality of life.

PMID- 21963054
TI  - From primary to secondary percutaneous coronary intervention: the emerging
      concept of early mechanical reperfusion with delayed facilitated stenting-when
      earlier may not be better.

PMID- 21963055
TI  - Cardiac computed tomography and risks of radiation exposure: how low can we go?

PMID- 21963056
TI  - Effect of delayed vs immediate stent implantation on myocardial perfusion and
      cardiac function in patients with ST-segment elevation myocardial infarction
      undergoing primary percutaneous intervention with thrombus aspiration.
AB  - BACKGROUND: Optimizing microcirculation in STEMI patients with thrombus
      containing lesion undergoing percutaneous coronary intervention (PCI) remains
      challenging. Our objective was to compare the effects on myocardial perfusion and
      cardiac function of delayed vs immediate stent implantation after thrombus
      aspiration in STEMI patients undergoing PCI. METHODS: Eighty-seven STEMI patients
      with thrombus-containing lesion undergoing PCI were enrolled. After thrombus
      aspiration was performed, subjects were divided into 2 groups according to
      residual thrombus score (TS): immediate stent implantation (ISI) group (n = 47,
      residual TS < 2; stenting was performed immediately), and delayed stent
      implantation (DSI) group (n = 40, residual TS >= 2; stenting was performed 7 days
      later). Corrected thrombolysis in myocardial infarction frame count and
      myocardial blush grade were analyzed immediately after PCI. The wall motion score
      index was assessed on admission and at 6-month follow-up. RESULTS: At the end of
      the PCI procedure, the corrected thrombolysis in myocardial infarction frame
      count was significantly shorter and the myocardial blush grade 3 was more
      frequent in the DSI group than in the ISI group. Compared with the ISI group, the
      DSI group had a lower incidence of thrombus-related angiographic events,
      including distal embolization and no reflow. A significantly greater improvement
      in wall motion score index from baseline to 6-month follow-up was observed in the
      DSI group compared with the ISI group. CONCLUSIONS: In STEMI patients presenting
      with thrombus containing lesion undergoing PCI, delayed stent implantation after
      thrombus aspiration leads to better myocardial perfusion and cardiac functional
      recovery in comparison with immediate stent implantation.

PMID- 21963057
TI  - Diagnostic performance of high-definition coronary computed tomography
      angiography performed with multiple radiation dose reduction strategies.
AB  - BACKGROUND: Numerous radiation dose reduction measures have been proposed for
      coronary computed tomographic angiography (CCTA). Although these techniques allow
      for imaging with reduced radiation, it is unknown whether diagnostic performance
      is maintained. A new high-definition CCTA (HD-CCTA) allows higher spatial
      resolution, reduced image noise, and lower radiation doses. OBJECTIVES: The aim
      of this study was to determine the diagnostic performance of HD-CCTA, in
      combination with multiple radiation dose reduction strategies, for the detection
      of obstructive coronary artery disease. METHODS: Consecutive patients (N = 43,
      aged 60 +/- 10 years, 83% male) with chest pain and referred for quantitative
      coronary angiography (QCA) underwent HD-CCTA with radiation dose reduction
      measures, including prospective electrocardiographic triggering, reduction of
      additional tube on-time, and minimization of tube voltage and current.
      Intraluminal diameter stenosis >= 50% was considered significant. QCA served as
      the reference standard. The area under the receiver-operating-characteristic
      curve (AUC) was used to evaluate diagnostic accuracy. RESULTS: All scans
      demonstrated diagnostic image quality, with 99% (543/548) of included coronary
      segments interpretable by HD-CCTA. Median effective radiation dose was 2.8 mSv
      (interquartile range, 1.3-3.9). The AUC for the per-patient assessment for
      stenosis >= 50% was 0.90 (95% confidence interval [CI], 0.77-0.96), with
      sensitivity of 95% (95% CI, 85%-100%), specificity of 79% (95% CI, 63%-95%),
      positive predictive value of 78% (95% CI, 61%-95%), and negative predictive value
      of 95% (95% CI, 85%-100%). CONCLUSIONS: Compared with QCA, HD-CCTA with multiple
      dose reduction measures resulted in low radiation doses and high diagnostic
      accuracy to detect and exclude obstructive coronary artery disease.

PMID- 21963058
TI  - Diagnosis, prevention, and management of statin adverse effects and intolerance:
      proceedings of a Canadian Working Group Consensus Conference.
AB  - While the proportion of patients with significant statin-associated adverse
      effects or intolerance is very low, the increasing use and broadening indications
      have led to a significant absolute number of such patients commonly referred to
      tertiary care facilities and specialists. This report provides a comprehensive
      overview of the evidence pertaining to a broad variety of statin-associated
      adverse effects followed by a consensus approach for the prevention, assessment,
      diagnosis, and management. The overview is intended both to provide clarification
      of the untoward effects of statins and to impart confidence in managing the most
      common issues in a fashion that avoids excessive ancillary testing and/or
      subspecialty referral except when truly necessary. The ultimate goal is to ensure
      that patients who warrant cardiovascular risk reduction can be treated optimally,
      safely, and confidently with statin medications or alternatives when warranted.

PMID- 21963059
TI  - Species-dependent sensitivity to contaminants: an approach using primary
      hepatocyte cultures with three marine fish species.
AB  - There is limited knowledge about the sensitivity of different fish species to
      environmental pollutants. Such information is pivotal in risk assessment and to
      understand why some species appear to be more tolerant to contaminants than
      others. The aim of the current study was to evaluate whether primary hepatocyte
      cultures of three marine fish species could be established in the field and
      whether their sensitivity to selected contaminants would differ. Primary
      hepatocyte cultures of three marine fish species (plaice, long rough dab,
      Atlantic cod) were established and exposed for 24 h to copper (20-2500 mg L-1)
      and statins (1-200 mg L-1). Endpoints were esterase activity, metabolic activity
      and reduced glutathione (GSH) content, all using fluorescent probes. Flatfish
      hepatocytes were more susceptible to copper and statin exposure than hepatocytes
      from cod. This study has shown that species-dependent differences in contaminant
      sensitivity can be investigated using primary hepatocyte cultures.

PMID- 21963060
TI  - THESEUS 1, FERONIA and relatives: a family of cell wall-sensing receptor kinases?
AB  - The plant cell wall provides form and integrity to the cell as well as a dynamic
      interface between a cell and its environment. Therefore mechanisms capable of
      policing changes in the cell wall, signaling cellular responses including those
      that would feedback regulate cell wall properties are expected to play important
      roles in facilitating growth and ensuring survival. Discoveries in the last few
      years that the Arabidopsis THESEUS 1 receptor-like kinase (RLK) may function as a
      sensor for cell wall defects to regulate growth and that its relatives FERONIA
      and ANXURs regulate pollen tube integrity imply strongly that they play key roles
      in cell wall-related processes. Furthermore, FERONIA acts as a cell surface
      regulator for RAC/ROP GTPases and activates production of reactive oxygen species
      which are, respectively, important molecular switches and mediators for diverse
      processes. These findings position the THESEUS 1/FERONIA family RLKs as surface
      regulators and potential cell wall sensors capable of broadly and profoundly
      impacting cellular pathways in response to diverse signals.

PMID- 21963061
TI  - Lower GI bleeding from ileocolonic histoplasmosis.

PMID- 21963062
TI  - The impact of video recording colonoscopy on adenoma detection rates.
AB  - BACKGROUND: The adenoma detection rate (ADR) is a quality benchmark for
      colonoscopy, influenced by several factors including bowel preparation,
      withdrawal time, and withdrawal technique. OBJECTIVE: To assess the impact of
      video recording of all colonoscopies on the ADR. DESIGN: Comparison of two
      cohorts of patients undergoing colonoscopy before and after implementation of
      video recording. SETTING: Academic outpatient endoscopy facility. PATIENTS: This
      study involved asymptomatic, average-risk adults undergoing screening
      colonoscopy. INTERVENTION: Video recording of all colonoscopy procedures. Polyp
      findings and withdrawal times were recorded for 208 consecutive screening
      colonoscopies. A policy of video recording all colonoscopies was implemented and
      announced to the staff. Data on another 213 screening colonoscopies were
      subsequently collected. MAIN OUTCOME MEASUREMENTS: Adenoma detection rate,
      withdrawal time, advanced polyp detection rate, hyperplastic polyp detection
      rate. RESULTS: At least one adenoma was found in 38.5% of patients after video
      recording versus 33.7% before video recording (P = .31). There was a significant
      increase in the hyperplastic polyp detection rate (44.1% vs 34.6%; P = .046).
      Most endoscopists had a numerical increase in their ADRs, but only one was
      significant (57.7% vs 22.6%; P < .01). There were trends toward higher detection
      of adenomas of <5 mm (59.1% vs 52%; P = .23) and right-sided adenomas (40.2% vs
      30.4%; P = .11) in the video recorded group. LIMITATIONS: No randomization,
      confounding of intervention effects, and sample size limitations. CONCLUSION:
      Video recording of colonoscopies is associated with a nonsignificant increase in
      the ADR and a significant increase in the hyperplastic polyp detection rate.
      There may be a benefit of video recording for endoscopists with low ADRs.

PMID- 21963063
TI  - Benefit of pronase in image quality during EUS.
AB  - BACKGROUND: EUS is useful for diagnosis of GI disease. However, artifacts caused
      by gastric mucus may worsen visibility during EUS. OBJECTIVE: To investigate the
      efficacy of premedication with pronase, the proteolytic enzyme, for improving
      imaging during EUS. DESIGN: Blinded, randomized, prospective study. SETTING:
      Tertiary-care referral center. PATIENTS: This study involved 183 patients
      scheduled for EUS. INTERVENTION: Patients were assigned to oral premedication
      with saline solution (group A), pronase and bicarbonate (group B), or pronase,
      bicarbonate, and simethicone (group C). Either conventional EUS or high-frequency
      catheter EUS (HFUS) was selected. Gastric cavity and gastric mucosal surface
      obscurity grades were assessed by using visibility scores from ultrasonographic
      images of each patient. MAIN OUTCOME MEASUREMENTS: Means of visibility scores and
      proportion of images with better visibility scores of the gastric cavity and
      gastric mucosal surface. Lower scores indicate better visibility of the gastric
      mucosal surface and fewer artifacts within the gastric cavity on conventional EUS
      and HFUS. RESULTS: Group B had significantly lower mean gastric cavity and
      gastric mucosal surface visibility scores than did groups A and C in both
      conventional EUS and HFUS. Group B also had a high proportion of images that had
      better gastric cavity and gastric mucosal surface visibility scores than did the
      other two groups in conventional EUS and HFUS. LIMITATIONS: Small number of
      patients and no assessment of the amount of mucus before oral premedication.
      CONCLUSION: Premedication for conventional EUS and HFUS by using a mixture of
      pronase and bicarbonate seems to decrease the number of gastric wall and lumen
      hyperechoic artifacts observed in patients given either saline solution or
      pronase/bicarbonate/simethicone.

PMID- 21963064
TI  - Endoscopic removal of migrated vascular embolic material from the duodenum with
      endovascular control.

PMID- 21963065
TI  - Endoscopic submucosal dissection for treatment of esophageal submucosal tumors
      originating from the muscularis propria layer.
AB  - BACKGROUND: The technique of endoscopic submucosal dissection (ESD), which was
      developed for en bloc resection of large lesions in the stomach, has been widely
      accepted for the treatment of early gastric cancer. It is being used for
      muscularis propria tumors of the digestive tract and has produced positive
      therapeutic effects. OBJECTIVE: To study the feasibility of ESD for the removal
      of esophageal muscularis propria tumors and to evaluate the efficacy and safety
      of ESD for this treatment. DESIGN: Single-center, retrospective study. SETTING:
      University hospital. PATIENTS: Thirty esophageal muscularis propria tumors from
      28 patients were treated with ESD between December 2008 and December 2010. We
      defined esophageal muscularis propria tumors as esophageal submucosal tumors
      originating from the muscularis propria layer. INTERVENTION: ESD. MAIN OUTCOME
      MEASUREMENTS: Tumor characteristics, complications, en bloc resection rate, and
      local recurrence rate were evaluated. RESULTS: Among the 28 patients, 11 were
      women (39.3%). The median age was 49.32 years (range 22-62 years). Mean (+/- SD)
      tumor size was 1.25 +/- 0.70 cm (range 0.5-3.0 cm). Except for 2 failed cases
      (one changed to surgery and the other changed to nylon ligation), 26 cases with
      28 tumors (2 cases had 2 tumors) originating from the muscularis propria of the
      esophagus were successfully resected by ESD. The en bloc resection rate was 93.3%
      (28/30). The median ESD procedure time was 73.5 minutes (range 30-120 minutes).
      Perforation occurred in 2 cases during dissection of the lesion, which was closed
      with metal endoclips. Pneumothorax occurred after the treatment in both cases.
      Closed thoracic drainages were initiated, and the patients recovered quickly
      without surgery. Pathological examination confirmed 27 leiomyomas and 1 GI
      stromal tumor. The curative resection rate was 100% (28/28). There was no
      recurrence during a 3 to 27-month follow-up period. LIMITATIONS: The limitation
      of the study was its retrospective design. CONCLUSION: ESD offers the promise of
      localized treatment of esophageal muscularis propria tumors with relatively few
      complications and low mortality. It makes the resection of whole lesions possible
      and provides precise histologic information.

PMID- 21963066
TI  - Single-balloon enteroscopy, magnetic resonance enterography, and abdominal US
      useful for evaluation of small-bowel disease in children with (suspected) Crohn's
      disease.
AB  - BACKGROUND: The usefulness of single-balloon enteroscopy (SBE) has not been
      evaluated in children with known or suspected Crohn's disease (CD). OBJECTIVE:
      The objectives of this study are to evaluate the diagnostic yield of SBE for
      pediatric CD by comparing it with US and magnetic resonance enterography (MRE).
      DESIGN: Single-center prospective study. SETTING: Tertiary-care referral
      hospital. PATIENTS: Between February 2009 and April 2010, 20 pediatric patients
      (ages 8-18 years) with suspected inflammatory bowel disease (IBD) or with a
      previous diagnosis of CD with suspected persistent small-bowel disease were
      enrolled. INTERVENTIONS: All patients underwent proximal and distal SBE, 17
      patients also underwent US combined with Doppler flow measurements, and 18
      underwent MRE. MAIN OUTCOME MEASUREMENTS: The findings of US with Doppler flow
      measurements and MRE were compared with those with SBE. RESULTS: The mean patient
      age was 15.0 years (range 11.3-18 years, 70% male). Of 14 patients with suspected
      IBD, 8 had a diagnosis of CD made after SBE. Activity in the small bowel was
      found in 14 patients (70%) with both suspected and previously diagnosed CD.
      Twelve patients (60%) had small-bowel disease that was out of reach of
      conventional endoscopy. Three patients (15%) had small-bowel activity solely in
      the jejunum, which was not detected by either MRE or US. LIMITATIONS: Single
      center study with small sample size. CONCLUSIONS: SBE can be used in children to
      accurately assess small-bowel disease and CD. Small-bowel activity may be
      identified by SBE in some patients in whom it may not be apparent despite use of
      conventional upper endoscopy, ileocolonoscopy, US with Doppler flow measurements,
      or MRE.

PMID- 21963067
TI  - EUS-guided biliary drainage with transluminal stenting after failed ERCP:
      predictors of adverse events and long-term results.
AB  - BACKGROUND: EUS-guided biliary drainage (EUS-BD) has been proposed as an
      effective alternative for percutaneous transhepatic biliary drainage (PTBD) after
      failed ERCP. To date, the risk factors for adverse events and long-term outcomes
      of EUS-BD with transluminal stenting (EUS-BDS) have not been fully explored.
      OBJECTIVE: To evaluate risk factors for adverse events and long-term outcomes of
      EUS-BDS. DESIGN: Prospective follow-up study. SETTING: Tertiary-care academic
      center. PATIENTS: This study involved 57 consecutive patients with malignant or
      benign biliary obstruction undergoing EUS-BDS after failed ERCP. INTERVENTION:
      EUS-guided hepaticogastrostomy (EUS-HGS) and EUS-guided choledochoduodenostomy
      with transluminal stenting (EUS-CDS). MAIN OUTCOME MEASUREMENTS: Risk factors for
      postprocedure and late adverse events and clinical outcomes of EUS-BDS. RESULTS:
      The overall technical and functional success rates, respectively, in the EUS-BDS
      group were 96.5% (intention-to-treat, n = 55/57) and 89% (per-protocol, n =
      49/55). Postprocedure adverse events developed after EUS-BDS in 11 patients (20%,
      n = 11/55). This included bile peritonitis (n = 2), mild bleeding (n = 2), and
      self-limited pneumoperitoneum (n = 7). In multivariate analysis, needle-knife use
      was the single risk factor for postprocedure adverse events after EUS-BDS (odds
      ratio 12.4; P = .01). A late adverse event in EUS-BDS was distal stent migration
      (7%, n = 4/55). The mean stent patencies with EUS-HGS and EUS-CDS were 132 days
      and 152 days, respectively. LIMITATIONS: Single-operator performed, nonrandomized
      study. CONCLUSION: EUS-HGS and EUS-CDS may be relatively safe and can be used as
      an alternative to PTBD after failed ERCP. Both techniques offer durable and
      comparable stent patency. The use of a needle-knife for fistula dilation in EUS
      BDS should be avoided if possible.

PMID- 21963068
TI  - Ultrathin endoscope-guided trangastric nasocystic irrigation tube placement to
      manage paracolic gutter extension of pancreatic necrosis.

PMID- 21963069
TI  - A randomized comparison of ultrathin and standard colonoscope in cecal intubation
      rate and patient tolerance.
AB  - BACKGROUND: Complete colonoscopy examination cannot be performed in as many as
      10% of cases. The new 9.2-mm ultrathin colonoscope (UTC) with an extra bending
      section may improve procedure tolerance and allow improvement in colonoscopy
      completion rate compared with a 12.9-mm standard colonoscope (SC). OBJECTIVE: To
      compare the performance of the 9.2-mm UTC with that of the 12.9-mm SC. DESIGN:
      Prospective, randomized, controlled trial. SETTING: Academic endoscopic unit.
      PATIENTS: Subjects 18 years and older undergoing their first colonoscopy.
      INTERVENTION: Subjects were randomized to either the UTC or SC group. MAIN
      OUTCOME MEASUREMENTS: First and rescue successful cecal intubation rates, subject
      satisfaction scores, and sedation requirements were compared. RESULTS: A total of
      1121 patients (56% women, mean age 53.6 years) were randomized to the UTC group
      (n = 551) or the SC group (n = 570). There was no statistically significant
      difference in the first successful cecal intubation rate between the UTC and SC
      groups (98.9% vs 97.4%, P = .057). The mean (standard deviation) dose of
      midazolam and pethidine used was significantly lower in the UTC group (2.65
      [0.65] mg vs 2.82 [0.85] mg, P < .001 and 27.6 [7.4] mg vs 29.7 [9.6] mg, P <
      .001, respectively). The mean (standard deviation) patient satisfaction score was
      similar between groups (6.99 [2.89] vs 7.04 [3.06], P = .762). Of the 21 patients
      (1.9%) with an incomplete initial colonoscopy (6 in the UTC group and 15 in the
      SC group), all 6 in the UTC group had their procedure completed with an SC.
      Eleven of 15 patients in the SC group had their procedures completed with a UTC
      in the same session. LIMITATIONS: Low failure rate may mask any difference
      between the 2 colonoscopes as a rescue instrument. CONCLUSIONS: The 9.2-mm UTC
      has performance characteristics similar to those of an SC in Chinese subjects
      undergoing their first colonoscopy performed by experienced and trainee
      endoscopists. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01142167.).

PMID- 21963070
TI  - Holmium laser lithotripsy under direct peroral cholangioscopy by using an ultra
      slim upper endoscope for patients with retained bile duct stones (with video).
AB  - BACKGROUND: Direct peroral cholangioscopy (POC) by using an ultra-slim endoscope
      provides direct visualization of the bile duct and allows for therapeutic
      intervention. Holmium laser lithotripsy can be effective for retained bile duct
      stones, but it requires direct visualization during the procedure for safe and
      effective fragmentation. Direct POC by using an ultra-slim endoscope may
      facilitate holmium laser lithotripsy. OBJECTIVE: To evaluate the feasibility,
      success rates, and complications of holmium laser lithotripsy under direct POC by
      using an ultra-slim endoscope for retained bile duct stones. DESIGN:
      Observational clinical feasibility study. SETTING: Tertiary-care referral center.
      PATIENTS: This study involved 13 patients with retained bile duct stones whose
      treatment failed by a conventional lithotripsy method involving mechanical
      lithotripsy. INTERVENTION: Holmium laser lithotripsy under direct POC by using an
      ultra-slim endoscope. MAIN OUTCOME MEASUREMENTS: Success rate of complete stone
      removal and procedure-related complications. RESULTS: Holmium laser lithotripsy
      under direct POC by using an ultra-slim endoscope was successful in 11 of 13
      patients (84.6%). Although direct POC was successful, holmium laser lithotripsy
      failed in 2 patients because of inaccurate targeting of the laser fiber to
      stones. There were no procedure-related complications except one case of mild
      pancreatitis. LIMITATIONS: A small number of patients and no comparison with
      other lithotripsy systems. CONCLUSION: Holmium laser lithotripsy under direct POC
      by using an ultra-slim endoscope was feasible and can be a safe endoscopic
      management method for retained bile duct stones.

PMID- 21963071
TI  - [Problems and advantages of autopsy in the case of out-of-hospital childhood
      death: report of 2 cases].
AB  - In France, the number of deaths remains high in the pediatric population. These
      deaths are rarely subject to a scientific or forensic autopsy. However, this
      medical act appears necessary to answer the many private and public questions
      (public health, prevention, judicial, or even institutional) that can arise. Two
      pediatric clinical observations raising these questions in the context of a
      household accident are presented. In the first one, the death led to the
      establishment of a forensic obstacle to the burial and a forensic autopsy. The
      autopsy results provided answers, both to the relatives and to the court. The
      second concerns a deceased child managed within the protocol for sudden infant
      death syndrome. The autopsy was not authorized by the parents and no answer on
      the causes of death could be determined. These 2 observations underline the
      importance and utility of this medical act.

PMID- 21963073
TI  - [Childhood parvovirus B19 encephalitis].
AB  - INTRODUCTION: Human parvovirus B19 (PVB19) causes erythema infectiosum or 5(th)
      disease in childhood, which mainly affects children between 3 and 15 years of
      age. PVB19 infections have also been described in association with a variety of
      neurologic manifestations including encephalitis. CASE REPORT: This 3-year 8
      month-old boy developed febrile encephalitis (mental status change with seizures
      and left limb hypertonia) associated with a rash. The electroencephalographs
      revealed focal slowing with some spikes in front of the left centro-temporo
      occipital areas ; bacteriological and biochemical cerebrospinal fluid (CSF)
      analysis were normal, brain radiologic studies (tomography and magnetic resonance
      imaging) were normal. The diagnosis of encephalitis associated with PVB19 primo
      infection was based on viral DNA detection in the serum and CSF using PCR and on
      the specific immunoglobulin M (without immunoglobulin G) detection in the serum.
      DISCUSSION: In France, encephalitis etiology is unknown in 48% of the cases.
      PVB19 accounts for 4.3% of undiagnosed meningoencephalitis in children. Although
      there is no specific sign, seizures and rash are reported in about one-half and
      one-quarter of cases, respectively. CONCLUSION: Even if PVB19 research is not
      cited in the French or American infectious disease society recommendations on the
      diagnosis and management of infectious encephalitis, this virus may be
      responsible, especially in cases of child febrile rash. Therefore, PVB19 research
      seems reasonable if the clinical presentation is concordant in children due to
      its diagnostic simplicity and efficacy.

PMID- 21963074
TI  - [Screening sensory and developmental disorders in nursery school children by the
      Maternal and Infant Protection Service in the Vaucluse (France) department:
      results, orientations, limits].
AB  - The aim of this study was to determine whether to continue the recommendations
      given by the doctors of the Maternal and Infant Protection (PMI) service within
      the medical check-ups given to nursery school children in the Vaucluse department
      in France. This was a longitudinal study conducted based on an observation grid
      from January to June 2009. A total of 2079 files were retained. This study
      revealed that more than one-quarter of the children for whom recommendations had
      been given no longer had care 3 months later; the main cause was the absence of
      adherence on the part of the family. This result emphasizes the limitation of the
      mass screenings conducted by the PMI in nursery schools: it raises the problem of
      access to healthcare for certain children and opens an opportunity for reflection
      on professional practices to optimize the mission of prevention and the promotion
      of health.

PMID- 21963075
TI  - [Pancreatic pseudocyst in children: what is the best therapeutic approach?].
AB  - INTRODUCTION: Pancreatic pseudocyst is an uncommon disorder in children and the
      majority of reported cases are secondary to trauma. AIM: Treatment options range
      from medical management to different forms of drainage procedure. The aim of this
      study was to discuss therapeutic strategies. OBSERVATIONS: The authors report
      herein pancreatic pseudocyst in four children aged 7, 9, 12, and 13 years with
      non-resolving pancreatic pseudocyst over a 2-year period from January 2006 to
      July 2008. The etiology of pancreatic pseudocyst was abdominal trauma in two
      cases and acute pancreatitis in two cases. Ultrasound and computed tomography
      scans confirmed the diagnosis. Two patients had endoscopic drainage. There were
      no procedure-related complications, nor was there a recurrence of the cyst. In
      one case, the pancreatic pseudocyst resolved spontaneously. CONCLUSION: This
      report suggests that children with non-spontaneously resolving pancreatic
      pseudocyst can be treated successfully and safely with endoscopic drainage.
      Surgical treatment remains an important alternative in the therapeutic
      armamentarium of this affection.

PMID- 21963076
TI  - [New treatments in pediatric rheumatology: effects, limits, and future
      developments].
AB  - Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases.
      International networks have enabled therapeutic trials of medications targeting
      tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6, or T-cell
      costimulation (abatacept). JIA-associated chronic uveitis may require the use of
      biotherapies that remain experimental in JIA, such as monoclonal antibodies to
      TNF-alpha. Systemic-onset JIA (also called childhood-onset Still's disease)
      raises specific treatment challenges and may require treatment with IL-1 or IL-6
      antagonists. Patients with JIA should be managed in specialized centers that have
      coordinated chains of care for the entire pediatric period and into adulthood. In
      addition, the use of recently introduced treatments in pediatric patients
      requires close monitoring for long-term side effects.

PMID- 21963077
TI  - [Congenital rubella still exists in Tunisia!].
AB  - Congenital rubella syndrome resulting from maternal rubella infection can cause
      serious multisystemic malformations resulting in severe morbidity and mortality.
      After immunization, its incidence has been reduced in the developed world, though
      it remains a real problem in developing countries since it causes many handicaps.
      In Tunisia, despite including rubella immunization in the routine national
      program on immunization for girls once they reach the age of 12, the congenital
      rubella syndrome still exists. We describe the clinical pattern and the outcome
      of congenital rubella syndrome in 2 infants and emphasize the necessity of
      recommending universal screening and follow-up vaccination of susceptible females
      and including rubella immunization in the routine national immunization program,
      especially in developing countries.

PMID- 21963078
TI  - Severity score for predicting pneumonia in inhalation injury patients.
AB  - Inhalation injuries contribute significantly to morbidity and mortality in both
      children and adults with burns. Pneumonia is a major compromising factor in these
      patients. The purpose of this article was to evaluate the characteristics, impact
      factors, incidence, morbidity, and mortality of pneumonia in inhalation injuries.
      Furthermore, a severity score has been formulated to help predict the probability
      of developing pneumonia following inhalation injuries. A retrospective study was
      performed of 214 patients, treated for inhalation injuries from 1999 to 2009 at
      the Burn Center in Chang Gung Memorial Hospital, Linkou, Taiwan. Patients'
      characteristics, length of hospitalization, total burn surface area, initial
      PaO2:FiO2 ratio, number of intubated days, bronchoscope grade, initial
      carboxyhemoglobin level (COHb) and mortality rate were recorded. A Student's t
      test was used for comparison of inhalation injury patients with and without
      pneumonia and was also used for comparing a TBSA of >20% to those with a TBSA of
      <=20% in patients with inhalation injury and pneumonia. Logistic regression
      analyses were utilized to create a severity score related to pneumonia. 129
      patients with inhalation injury were included in the analysis. Overall, 38%
      (49/129) patients developed pneumonia. Pneumonia associated with inhalation
      injury occurred more often in patients with a TBSA>20% (P<0.05). The intubation
      days, bronchoscope grade and COHb level of pneumonia patients were significantly
      longer (P<0.05). Initial PaO2:FiO2 ratio (PaO2/FiO2) was significantly lower in
      patients with pneumonia (P<0.05). Mortality following pneumonia was increased
      sevenfold (P<0.05). Hospitalization days and intubation days were significantly
      longer in TBSA>20%. Logistic regression analysis was performed to find out the
      impact factors of pneumonia in inhalation injury patients and to set a severity
      score. Patients age >60 years, TBSA >20%, bronchoscope grade is 3 or 4, initial
      PaO2/FiO2?300 and initial COHb level>10% showed a significant difference
      (P<0.05). The total severity scale was set at 5 points. Each impact factor was
      given one point and when the score >=2 it means patients have high risk of
      development of pneumonia. This study had identified the significant risk factors
      for potential development of pneumonia in a group of inhalation injury patients.
      The impact of these risk factors should be validated in further prospective
      trials to improve outcome or at least reduce the incidence of the surrogate
      diagnosis of pneumonia.

PMID- 21963079
TI  - Double opposing rectangular advancement flap is an alternative technique in the
      treatment of wide linear postburn scar contractures.
AB  - BACKGROUND: Double opposing rectangular advancement is a new and alternative
      technique in the treatment of postburn scar contractures. The technique consists
      of opposing two adjacent subcutaneously pedicled rectangular flaps by advancement
      and lengthening a contracture band. Experimental studies demonstrated that the
      technique is efficient to elongate a tension line as much as Z-plasty in the rat
      inguinal skin. In this clinical study we investigated the efficiency and
      versatility of the technique in the treatment of wide linear postburn scar
      contractures in various parts of the body. MATERIALS AND METHOD: We applied 16
      double opposing rectangular advancement in 7 patients (aged 4-56). Flaps were
      applied in the upper extremity (11 flaps), lower extremity (4 flaps) and trunk (1
      flap). RESULTS: Average follow-up was 1-year. All flaps achieved adequate
      relaxation postoperatively and healed uneventfully. Postoperative measurements
      indicated that the lengthening provided with the technique ranged from 72 to
      100%. The subcutaneous pedicle of the rectangular flaps provided a distinct
      advantage in terms of vascularity. Recontracture was seen in one patient to whom
      two double opposing rectangular flaps in series were applied in the axilla.
      CONCLUSION: Clinical results indicated that double opposing rectangular
      advancement is effective in the treatment of wide linear postburn scar
      contractures. Preoperative planning and application of flaps are simple. One
      knows preoperatively the exact elongation along the contracture line and
      narrowing perpendicular to this line which will be provided with the technique.
      Since the flaps are subcutaneously pedicled, the vascularity of the flaps are
      reliable. However the technique may not avoid recontracture in the axilla.

PMID- 21963080
TI  - Carotid intima-media thickness is increased in patients with
      mucopolysaccharidoses.
AB  - BACKGROUND: The feasibility of carotid artery intima-media thickness (C-IMT), an
      established cardiovascular disease marker, as a cardiac risk marker in
      mucopolysaccharidosis (MPS) patients was explored. OBJECTIVES: To determine if C
      IMT is abnormal in MPS versus unaffected controls, and if C-IMT correlates with
      coronary artery diameter in MPS. MATERIAL AND METHODS: Measurements of C-IMT via
      neck ultrasound and echocardiographic parameters, including coronary artery
      diameters, were obtained from MPS and control patients, and compared. RESULTS:
      Sixteen MPS subjects (6 MPS I, 6 MPS II, 2 MPS III, 1 MPS VI, 1 MPS VII) and
      sixteen age, ethnicity, and gender-matched controls were enrolled. Median MPS and
      control subject ages were 8.3+/-4.5 and 8.6+/-4.3 years, respectively (p=0.73).
      Mean MPS and control C-IMTs were 0.54+/-0.070 and 0.48+/-0.034 mm (p=0.0029). No
      differences in left main, left anterior descending, or right coronary artery
      diameters were seen between MPS and controls. A significant proportion of MPS
      subjects had mitral insufficiency (14/16; p=0.0002), aortic insufficiency (10/16;
      p=0.0021), and left ventricular dilatation (7/16, p=0.037) versus controls. C-IMT
      did not correlate significantly with age, height, weight, coronary measurements,
      or duration of treatment. CONCLUSION: C-IMT in MPS patients is increased compared
      to matched controls, likely reflective of arterial intima-medial
      glycosaminoglycan accumulation. MPS subjects demonstrated a high percentage of
      left-sided valvular insufficiency and ventricular dilatation. Additional studies
      should be performed in MPS patients to determine if C-IMT correlates with
      arterial elasticity, biomarkers of vascular dysfunction, and higher risk of
      cardiovascular events.

PMID- 21963081
TI  - Shared genetic variance between the features of the metabolic syndrome:
      heritability studies.
AB  - Heritability estimates of MetS range from approximately 10%-30%. The genetic
      variation that is shared among MetS features can be calculated by genetic
      correlation coefficients. The objective of this paper is to identify MetS feature
      as well as MetS related features which have much genetic variation in common, by
      reviewing the literature regarding genetic correlation coefficients.
      Identification of features, that have much genetic variation in common, may
      eventually facilitate the search for pleitropic genetic variants that may explain
      the clustering of MetS features. A PubMed search with the search terms
      "(metabolic syndrome OR insulin resistance syndrome) and (heritability OR genetic
      correlation OR pleiotropy)" was performed. Studies published before 7th July
      2011, which presented genetic correlation coefficients between the different MetS
      features and genetic correlation coefficients of MetS and its features with
      adipose tissue-, pro-inflammatory and pro-thrombotic biomarkers were included.
      Nine twin and 19 family studies were included in the review. Genetic correlations
      varied, but were strongest between waist circumference and HOMA-IR (r(2): 0.36 to
      0.79, median: 0.50), HDL cholesterol and triglycerides (r(2): -0.05 to -0.59,
      median -0.45), adiponectin and MetS (r(2): -0.32 to -0.43; median -0.38),
      adiponectin and insulin (r(2): -0.10 to -0.60; median -0.30) and between
      adiponectin and HDL-cholesterol (r(2): -0.22 to -0.51, median -0.29). In
      conclusion, heritability studies suggest that genetic pleiotropy exist especially
      between certain MetS features, as well as between MetS and adiponectin. Further
      research on actual genetic variants responsible for the genetic pleiotropy of
      these combinations will provide more insight into the etiology of MetS.

PMID- 21963082
TI  - Chronic management and health supervision of individuals with propionic acidemia.
AB  - Propionic acidemia is a relatively rare inborn error of metabolism. Individuals
      with propionic acidemia often have life-threatening episodes of hyperammonemia
      and metabolic acidosis, as well as intellectual disability. There are many
      reports of additional problems, including poor growth, stroke-like episodes of
      the basal ganglia, seizures, cardiomyopathy, long QTc syndrome, immune defects,
      pancreatitis and optic neuropathy; however, there is little information about the
      incidence of these problems in this rare disease. Additionally, there are no
      clear guidelines for medical or surgical management of individuals with propionic
      acidemia. Through a comprehensive and systematic review of the current medical
      literature and survey of expert opinion, we have developed practice guidelines
      for the chronic management of individuals with propionic acidemia, including
      dietary therapy, use of medications, laboratory monitoring, chronic health
      supervision, use of gastrostomy tubes and liver transplantation.

PMID- 21963083
TI  - Allelic variations in superoxide dismutase-1 (SOD1) gene are associated with
      increased risk of diabetic nephropathy in type 1 diabetic subjects.
AB  - BACKGROUND: Oxidative stress is involved in the pathophysiology of diabetic
      nephropathy. The superoxide dismutase (SOD) enzymes play a major role in
      detoxification of reactive oxygen species and have a protective effect against
      diabetic nephropathy. We investigated associations of allelic variations in SOD1
      gene with nephropathy in patients with type 1 diabetes. METHODS: Seven SNPs in
      SOD1 region were analyzed in 1285 type 1 European Caucasian diabetic patients
      from the SURGENE prospective study (n=340; ten year follow-up), and the Genesis
      France-Belgium (n=501) and GENEDIAB (n=444) cross-sectional studies. Cox
      proportional hazards and logistic regression analyses were used to estimate
      hazard ratios or odds ratios for incidence and prevalence of diabetic
      nephropathy. RESULTS: In the SURGENE study, the T-allele of rs1041740 was
      associated with the prevalence of incipient (OR 5.75, 95% CI 1.78-19.39, p=0.004)
      and established/advanced nephropathy at baseline (OR 8.95, 95% CI 1.51-58.42,
      p=0.02), and with the incidence of incipient nephropathy during follow-up (HR
      1.46, 95% C.I. 1.13-1.90, p=0.004). The variant was also associated with
      decreased estimated glomerular filtration rate (eGFR) throughout the study. In
      cross-sectional study of Genesis/GENEDIAB cohorts, the G-allele of rs17880135 was
      associated with incipient (OR 7.53, 95% CI 2.30-25.45, p=0.001), established (OR
      6.04, 95% CI 1.52-23.91, p=0.01) and advanced nephropathy (OR 10.03, 95% CI 2.95
      35.44, p=0.0003). CONCLUSIONS: SOD1 allelic variations were associated with the
      prevalence of diabetic nephropathy, with the incidence of microalbuminuria and
      with decreased eGFR in type 1 diabetic subjects. These results are consistent
      with an implication of oxidative stress in the pathophysiology of diabetic
      nephropathy and with the major role for antioxidant enzymes as a mechanism of
      renal protection.

PMID- 21963084
TI  - Perfluorinated alkyl acids in water, sediment and wildlife from Sydney Harbour
      and surroundings.
AB  - Perfluorinated alkyl compounds (PFCs) including perfluorooctane sulphonate (PFOS)
      and perfluorooctanoate (PFOA) were measured in environmental samples collected
      from around Homebush Bay, an urban/industrial area in the upper reaches of Sydney
      Harbour and Parramatta River estuary. Water, surface sediment, Sea Mullet (Mugil
      cephalus), Sydney Rock Oyster (Saccostrea commercialis) and eggs of two bird
      species; White Ibis (Threskiornis molucca), and Silver Gull (Larus
      novaehollandiae) were analysed. In most samples PFOS was the dominant PFC.
      Geometric mean PFOS concentrations were 33 ng/gww (wet weight) in gull eggs, 34
      ng/gww in ibis eggs, and 1.8 ng/gww and 66 ng/gww in Sea Mullet muscle and liver,
      respectively. In sediment the PFOS geometric mean was 1.5 ng/g, in water average
      PFOS and PFOA concentrations ranged from 7.5 to 21 ng/L and 4.2 to 6.4 ng/L,
      respectively. In oysters perfluorododecanoic acid was most abundant, with a
      geometric mean of 2.5 ng/gww.

PMID- 21963085
TI  - Current consensus on the management of primary sclerosing cholangitis.
AB  - Guidelines for the management of primary sclerosing cholangitis (PSC) have
      recently been published by both the European Association for the Study of the
      Liver (EASL) and the American Association for the Study of Liver Diseases
      (AASLD). The current review focuses on the management of PSC, based on these
      guidelines. There is no established medical therapy for PSC. The role for UDCA in
      slowing the disease progression and improving survival is as yet unclear, and
      there are no specific recommendations for the general use of UDCA in this
      condition. Guidelines recommend that dominant bile duct strictures with
      significant cholestasis should be treated with biliary dilatation, with or
      without stenting. Prospective studies to define type, duration, optimal frequency
      and long-term effects of endoscopic therapy are needed. Liver transplantation is
      recommended for end stage disease and has excellent results. PSC patients with
      dysplasia in biliary brush cytology specimens should also be considered for
      transplantation. There is no evidence-based algorithm for the follow-up of PSC
      patients, but some regular investigations are recommended (surveillance
      colonoscopies in patients with IBD and ultrasound to detect gallbladder mass
      lesions).

PMID- 21963086
TI  - Liver transplantation and hepatitis C.
AB  - Hepatitis C virus (HCV)-related end-stage cirrhosis with/without hepatocellular
      carcinoma is the primary indication for liver transplantation in many countries.
      Unfortunately, HCV is not eliminated by transplantation and graft re-infection is
      the rule, resulting in HCV-related graft disease. The natural history of
      recurrent hepatitis is variable; overall, progression to cirrhosis occurs in 20
      30% and allograft failure in 10% after 5-10 years from transplantation. The use
      of poor quality organs, particularly from old donors, has a significant negative
      impact on disease severity and transplant outcome. In contrast, antiviral
      therapy, particularly if it results in permanent eradication of the virus, is
      associated with improved histology, reduced rate of graft decompensation and
      enhanced outcome. Disease monitoring, through protocol liver biopsies and new non
      invasive tools, is essential to select patients at need of antiviral therapy.
      Peginterferon with ribavirin, used similarly to what is done in the non
      transplant setting, is currently the treatment of choice; sustained viral
      response is achieved in about 35% of cases. Side effects, particularly anemia,
      are extremely frequent and sometimes severe (rejection, de novo autoimmune
      hepatitis). Retransplantation (RT) is the last option for the small subset of
      patients with allograft failure due to HCV recurrence who fulfil minimum criteria
      based on RT survival models.

PMID- 21963087
TI  - IgG4-related sclerosing disease: autoimmune pancreatitis (AIP) and IgG4-related
      cholangitis.

PMID- 21963088
TI  - Maintaining CD4-CD8 lineage integrity in T cells: where plasticity serves
      versatility.
AB  - The divergence of the two alphabeta T cell subsets defined by the mutually
      exclusive expression of CD4 and CD8 glycoproteins is an important event during
      the intrathymic differentiation of T lymphocytes. This reviews briefly summarizes
      the mechanisms that promote commitment to the CD4 or CD8 lineage in the thymus,
      and discusses the transcription factor circuits and epigenetic mechanisms that
      concur to maintain lineage integrity in post-thymic cells and yet allow effector
      cell differentiation.

PMID- 21963089
TI  - Arc in synaptic plasticity: from gene to behavior.
AB  - The activity-regulated cytoskeletal (Arc) gene encodes a protein that is critical
      for memory consolidation. Arc is one of the most tightly regulated molecules
      known: neuronal activity controls Arc mRNA induction, trafficking and
      accumulation, and Arc protein production, localization and stability. Arc
      regulates synaptic strength through multiple mechanisms and is involved in
      essentially every known form of synaptic plasticity. It also mediates memory
      formation and is implicated in multiple neurological diseases. In this review, we
      will discuss how Arc is regulated and used as a tool to study neuronal activity.
      We will also attempt to clarify how its molecular functions correspond to its
      requirement in various forms of plasticity, discuss Arc's role in behavior and
      disease, and highlight critical unresolved questions.

PMID- 21963091
TI  - The importance of chemotherapy and radiation in uterine papillary serous
      carcinoma.
AB  - PURPOSE: To identify prognostic and predictive factors of overall survival (OS),
      relapse-free survival (RFS) and toxicity for patients with uterine papillary
      serous carcinoma (UPSC). MATERIALS AND METHODS: Patient, tumor, treatment and
      relapse characteristics of 135 women with Stages I-IVA UPSC treated between 1980
      and 2006 at Dana-Farber/Brigham and Women's Cancer Center (DF/BWCC) were analyzed
      using Cox regression models to determine prognostic and predictive factors for
      OS, RFS and toxicity. RESULTS: Mean follow-up was 5.5 years (range, 0.01-25.2).
      Median 5-year OS was 52%, and RFS was 42% for all patients. On Cox regression
      analysis, increasing age, stage, and myometrial invasion were prognostic factors
      associated with shorter OS and RFS. A paclitaxel-platinum chemotherapy regimen
      was significantly associated with longer OS (hazard ratio [HR]=0.34, 95%
      confidence interval [CI] 0.15-0.74, p=0.007) and RFS (HR=0.45, 95% CI 0.22-0.92,
      p=0.03). RFS was improved for patients treated with RT (HR=0.44, 95% CI 0.25
      0.77, p=0.004). The 5-year grade 3+ toxicity rate was 3.5% for those who received
      RT and was 2.9% for those who did not (p=NS). CONCLUSION: Uterine papillary
      serous cancer can be an aggressive tumor type with a poor prognosis. RFS was
      improved by radiation and chemotherapy with few grade 3 or higher complications.
      Using radiation and paclitaxel-platinum chemotherapy should be attempted whenever
      feasible for patients with UPSC who do not have distant metastases at diagnosis.

PMID- 21963090
TI  - Emerging roles of resolvins in the resolution of inflammation and pain.
AB  - Resolvins, including D and E series resolvins, are endogenous lipid mediators
      generated during the resolution phase of acute inflammation from the omega-3
      polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid
      (EPA). Resolvins have potent anti-inflammatory and pro-resolution actions in
      several animal models of inflammation. Recent findings also demonstrate that
      resolvin E1 and resolvin D1 can each potently dampen inflammatory and
      postoperative pain. This review focuses on the mechanisms by which resolvins act
      on their receptors in immune cells and neurons to normalize exaggerated pain via
      regulation of inflammatory mediators, transient receptor potential (TRP) ion
      channels, and spinal cord synaptic transmission. Resolvins may offer novel
      therapeutic approaches for preventing and treating pain conditions associated
      with inflammation.

PMID- 21963092
TI  - Cervical cancer survival for patients referred to a tertiary care center in
      Kentucky.
AB  - OBJECTIVES: To identify prognostic factors influencing cervical cancer survival
      for patients referred to a tertiary care center in Kentucky. METHODS: A cohort
      study was performed to assess predictive survival factors of cervical cancer
      patients referred to the University of Kentucky from January 2001 to May 2010.
      Eligibility criteria included those at least 18 years-old, cervical cancer
      history, and no prior malignancy. Descriptive statistics were compiled and
      univariable and multivariable Cox proportional hazard analysis were performed.
      RESULTS: 381 patients met entry criteria. 95% were Caucasian (N=347) and 66%
      (N=243) lived in Appalachian Kentucky. The following covariates showed no
      evidence of a statistical association with survival: race, body mass index,
      residence, insurance status, months between last normal cervical cytology and
      diagnosis, histology, tumor grade, and location of primary radiation treatment.
      After controlling for identified significant variables, stage of disease was a
      significant predictor of overall survival, with estimated relative hazards
      comparing stages II, III, and IV to stage I of 3.09 (95% CI: 1.30, 7.33), 18.11
      (95% CI: 7.44, 44.06), and 53.03(95% CI: 18.16, 154.87), respectively. The
      presence of more than two comorbid risk factors and unemployment was also
      correlated with overall survival [HR 4.25 (95% CI: 1.00, 18.13); HR 2.64 (95% CI
      1.29, 5.42), respectively]. CONCLUSIONS: Residence and location of treatment
      center are not an important factor in cervical cancer survival when a tertiary
      cancer center can oversee and coordinate care; however, comorbid risk factors
      influence survival and further exploration of disease comorbidity related to
      cervical cancer survival is warranted.

PMID- 21963093
TI  - Serum 25-hydroxyvitamin D concentration and arterial stiffness among type 2
      diabetes.
AB  - AIM: To evaluate the association between serum 25-hydroxyvitamin D [25(OH)D] and
      arterial stiffness in patients with type 2 diabetes. METHODS: Serum 25(OH)D was
      measured in a cross-sectional sample of 131 men and 174 women aged 30 years and
      over in Korea. Arterial stiffness was assessed by pulse wave velocity (PWV)
      obtained with a VP-2000 pulse wave unit. Fasting plasma glucose, insulin, lipid
      profile, HbA1c, calcium, phosphorous, and HS-CRP were measured. RESULTS: The
      prevalence of vitamin D deficiency was high (85.9%). Those with lower vitamin D
      levels had increased PWV. Using multivariate regression analysis, low 25(OH)D
      concentrations independently predicted PWV (p<0.001) in people with type 2
      diabetes after adjustment for other risk factors such as age, smoking,
      hypertension, HS-CRP, diabetes duration, hypertension duration, HbA1c, and BMI.
      CONCLUSIONS: Vitamin D deficiency is common in type 2 diabetes, and a low 25(OH)D
      level is significantly associated with increased arterial stiffness in these
      patients. Vitamin D may influence the development of cardiovascular disease.
      Clinical intervention studies are needed to clarify whether treatment with
      vitamin D decreases the risk of cardiovascular disease in patients with type 2
      diabetes.

PMID- 21963094
TI  - Global identification of modular cullin-RING ligase substrates.
AB  - Cullin-RING ligases (CRLs) represent the largest E3 ubiquitin ligase family in
      eukaryotes, and the identification of their substrates is critical to
      understanding regulation of the proteome. Using genetic and pharmacologic Cullin
      inactivation coupled with genetic (GPS) and proteomic (QUAINT) assays, we have
      identified hundreds of proteins whose stabilities or ubiquitylation status are
      regulated by CRLs. Together, these approaches yielded many known CRL substrates
      as well as a multitude of previously unknown putative substrates. We demonstrate
      that one substrate, NUSAP1, is an SCF(Cyclin F) substrate during S and G2 phases
      of the cell cycle and is also degraded in response to DNA damage. This collection
      of regulated substrates is highly enriched for nodes in protein interaction
      networks, representing critical connections between regulatory pathways. This
      demonstrates the broad role of CRL ubiquitylation in all aspects of cellular
      biology and provides a set of proteins likely to be key indicators of cellular
      physiology.

PMID- 21963095
TI  - Towards a reliable technology for antioxidant capacity and oxidative damage
      evaluation: electrochemical (bio)sensors.
AB  - To counteract and prevent the deleterious effect of free radicals the living
      organisms have developed complex endogenous and exogenous antioxidant systems.
      Several analytical methodologies have been proposed in order to quantify
      antioxidants in food, beverages and biological fluids. This paper revises the
      electroanalytical approaches developed for the assessment of the total or
      individual antioxidant capacity. Four electrochemical sensing approaches have
      been identified, based on the direct electrochemical detection of antioxidant at
      bare or chemically modified electrodes, and using enzymatic and DNA-based
      biosensors.

PMID- 21963096
TI  - Quantum dot-based immunochromatography test strip for rapid, quantitative and
      sensitive detection of alpha fetoprotein.
AB  - Rapid, quantitative detection of tumor markers with high sensitivity and
      specificity is critical to clinical diagnosis and treatment of cancer. We
      describe here a novel portable fluorescent biosensor that integrates quantum dot
      (QD) with an immunochromatography test strip (ICTS) and a home-made test strip
      reader for detection of tumor markers in human serum. Alpha fetoprotein (AFP),
      which is valuable for diagnosis of primary hepatic carcinoma, is used as a model
      tumor marker to demonstrate the performance of the proposed immunosensor. The
      principle of this sensor is on the basis of a sandwich immunoreaction that was
      performed on an ICTS. The fluorescence intensity of captured QD labels on the
      test line and control line served as signals was determined by the home-made test
      strip reader. The strong luminescence and robust photostability of QDs combined
      with the promising advantages of an ICTS and sensitive detection with the test
      strip reader result in good performance. Under optimal conditions, this biosensor
      is capable of detecting as low as 1 ng/mL AFP standard analyte in 10 min with
      only 50 MUL sample volume. Furthermore, 1000 clinical human serum samples were
      tested by both the QD-based ICTS and a commercial electrochemiluminescence
      immunoassay AFP kit simultaneously to estimate the sensitivity, specificity and
      concordance of the assays. Results showed high consistency except for 24 false
      positive cases (false positive rate 3.92%) and 17 false negative cases (false
      negative rate 4.38%); the error rate was 4.10% in all. This demonstrates that the
      QD-based ICTS is capable of rapid, sensitive, and quantitative detection of AFP
      and shows a great promise for point-of-care testing of other tumor markers.

PMID- 21963097
TI  - Comparison of anterior cruciate ligament tunnel position and graft obliquity with
      transtibial and anteromedial portal femoral tunnel reaming techniques using high
      resolution magnetic resonance imaging.
AB  - PURPOSE: Using 3-dimensional high-resolution magnetic resonance imaging (MRI), we
      sought to compare femoral and tibial tunnel position and resultant graft
      obliquity with single-bundle anterior cruciate ligament (ACL) reconstruction
      using transtibial (TT) or anteromedial (AM) portal femoral tunnel reaming
      techniques. METHODS: Thirty patients were prospectively enrolled after primary,
      autogenous bone-patellar tendon-bone ACL reconstruction by 2 groups of high
      volume, fellowship-trained sports medicine surgeons. With the TT technique, an
      external starting point was used to maximize graft obliquity and femoral
      footprint capture. By use of high-resolution MRI and imaging analysis software,
      bilateral 3-dimensional knee models were created, mirrored, and superimposed.
      Differences between centroids for each femoral and tibial insertion, as well as
      corresponding ACL/graft obliquity, were evaluated with paired t tests and 2-sided
      Mann-Whitney nonparametric tests, with P < .05 defined as significant. RESULTS:
      No significant differences were observed between groups in position of
      reconstructed femoral footprints. However, on the tibial side, AM centroids
      averaged 0.8 +/- 1.9 mm anterior to native ACL centroids, whereas the TT group
      centered 5.23 +/- 2.4 mm posterior to native ACL centroids (P < .001). Sagittal
      obliquity was closely restored with the AM technique (mean, 52.2 degrees  v. 53.5
      degrees  for native ACL) but was significantly more vertical (mean, 66.9 degrees
      ) (P = .0001) for the TT group. CONCLUSIONS: In this clinical series, AM portal
      femoral tunnel reaming more accurately restored native ACL anatomy than the TT
      technique. Although both techniques can capture the native femoral footprint with
      similar accuracy, the TT technique requires significantly greater posterior
      placement of the tibial tunnel, resulting in decreased sagittal graft obliquity.
      When a tibial tunnel is drilled without the need to accommodate subsequent
      femoral tunnel reaming, more accurate tibial tunnel position and resultant
      sagittal graft obliquity are achieved. LEVEL OF EVIDENCE: Level III,
      retrospective comparative study.

PMID- 21963098
TI  - Surgical intervention after transvaginal Prolift mesh repair: retrospective
      single-center study including 524 patients with 3 years' median follow-up.
AB  - OBJECTIVE: The aim of this study was to explore the nature and rate of surgical
      intervention after transvaginal Prolift mesh repair for pelvic organ prolapse.
      STUDY DESIGN: This was a retrospective study of all patients who underwent
      Prolift mesh repair between January 2005 and January 2009. Patient data were
      obtained from medical records, and patients were telephoned to check if they had
      surgery in other hospitals. RESULTS: A total of 600 consecutive patients were
      identified. Of these, 524 patients (87.3%) were included in the study, with a
      median follow-up duration of 38 months (range, 15-63). Global reoperation rate
      was 11.6%. Indications of intervention were surgery for urinary incontinence
      (6.9%), mesh-related complications (3.6%), or prolapse recurrence (3%).
      CONCLUSION: The global reoperation rate after transvaginal Prolift mesh repair
      was 11.6%, with urinary incontinence surgery being the most common indication.
      Rates of mesh complications and prolapse recurrence are relatively low in an
      experienced team.

PMID- 21963099
TI  - Optimization of near-infrared fluorescent sentinel lymph node mapping for vulvar
      cancer.
AB  - OBJECTIVES: Near-infrared fluorescence imaging has the potential to improve
      sentinel lymph node mapping in vulvar cancer, which was assessed in the current
      study. Furthermore, dose optimization of indocyanine green adsorbed to human
      serum albumin was performed. STUDY DESIGN: Nine vulvar cancer patients underwent
      the standard sentinel lymph node procedure using (99m)technetium-nancolloid and
      patent blue. In addition, intraoperative imaging was performed after peritumoral
      injection of 1.6 mL of 500, 750, or 1000 MUM of indocyanine green adsorbed to
      human serum albumin. RESULTS: Near-infrared fluorescence sentinel lymph node
      mapping was successful in all patients. A total of 14 sentinel lymph nodes
      (average, 1.6; range, 1-4) were detected: 14 radioactive (100%), 11 blue (79%),
      and 14 near-infrared fluorescent (100%). CONCLUSION: This study demonstrates
      feasibility and accuracy of sentinel lymph node mapping using indocyanine green
      adsorbed to human serum albumin. Considering safety, cost, and pharmacy
      preferences, an indocyanine green adsorbed to human serum albumin concentration
      of 500 MUM appears optimal for sentinel lymph node mapping in vulvar cancer.

PMID- 21963100
TI  - The senior obstetrician requesting obstetric privileges.
AB  - As the American physician workforce matures in age, senior physicians on the
      active clinical staff may become vulnerable to diminished professional
      performance. Many physicians compensate by using experiential rather than
      analytic methods to effectively solve clinical problems. Surgical expertise also
      may be at risk in these circumstances. Organized medical staffs must confront
      these realities before adverse events are reported as patient safety is their
      primary responsibility. The appropriate credentialing process will enable
      talented and experienced senior clinicians to continue to provide high quality
      medical care.

PMID- 21963101
TI  - Selenium in reproductive health.
AB  - Selenium is an essential trace element of importance to human biology and health.
      Increasing evidence suggests that this mineral plays an important role in normal
      growth and reproduction in animals and humans, and selenium supplementation is
      now recommended as part of public health policy in geographical areas with severe
      selenium deficiency in soil. This review addresses the biological functions of
      selenium followed by a detailed review of associations between selenium status
      and reproductive health. In many countries, selenium dietary intake falls below
      the recommended nutrient intakes and is inadequate to support maximal expression
      of the selenoenzymes. Numerous reports implicate selenium deficiency in several
      reproductive and obstetric complications including male and female infertility,
      miscarriage, preeclampsia, fetal growth restriction, preterm labor, gestational
      diabetes, and obstetric cholestasis. Currently, there is inadequate information
      from the available small intervention studies to inform public health strategies.
      Larger intervention trials are required to reinforce or refute a beneficial role
      of selenium supplementation in disorders of reproductive health.

PMID- 21963102
TI  - Blood loss after cesarean delivery: a registry-based study in Norway, 1999-2008.
AB  - OBJECTIVE: The objective of the study was to assess risk factors for moderate and
      severe blood loss after cesarean delivery (CD). STUDY DESIGN: All planned (n =
      32,716) and emergency (n = 47,942) cesareans, as reported over a 10-year period
      to the Medical Birth Registry of Norway, were analyzed separately in a case
      control design. Women with moderate (500 to <=1500 mL) or severe (>1500 mL) blood
      loss were analyzed with women with blood loss less than 500 mL as controls in
      SPSS (version 17.0) with chi(2) test and logistic regression. RESULTS: The
      prevalence of severe blood loss was consistently higher in emergency (3.2%) than
      planned CD (1.9%). Planned and emergency CDs share common risk factors for both
      moderate and severe blood loss, whereas emergency CD carries in addition delivery
      related risk factors. CONCLUSION: When revising management schemes for CD,
      anesthetic procedures should be reconsidered as surgical competence in cases with
      placenta previa, placental abruption, and low hemoglobin.

PMID- 21963104
TI  - Efficacy and safety of oxybutynin chloride topical gel for women with overactive
      bladder syndrome.
AB  - OBJECTIVE: This subgroup analysis of a phase-3 study evaluated the efficacy and
      safety of oxybutynin chloride topical gel (OTG) in women with overactive bladder
      syndrome (OAB). STUDY DESIGN: Women (n = 704) with urgency-predominant urinary
      incontinence received OTG or placebo for 12 weeks. The primary endpoint was
      change from baseline to last observation in number of daily incontinence
      episodes. Treatments were compared with the use of analysis of covariance.
      RESULTS: OTG significantly reduced the number (mean +/- standard deviation) of
      daily incontinence episodes (OTG, -3.0 +/- 2.8 episodes; placebo, -2.5 +/- 3.0
      episodes; P < .0001), reduced urinary frequency (P = .0013), increased voided
      volume (P = .0006), and improved select health-related quality-of-life domains (P
      <= .0161) vs placebo. Dry mouth was the only drug-related adverse event
      significantly more common with OTG (7.4%) than with placebo (2.8%; P = .0062).
      CONCLUSION: OTG was well tolerated and provided significant improvement in
      urinary symptoms and health-related quality of life in women with OAB.

PMID- 21963105
TI  - A comparison of duration of first prescribed insulin therapy in uncontrolled type
      2 diabetes.
AB  - AIMS: We investigated whether differences in duration of first insulin use in
      type 2 diabetes remain after adjustment for potential confounders, and what
      factors are associated with longer use. METHODS: People prescribed a first
      insulin (2000-2007) after 2-3 non-insulin glucose lowering treatments (OGLD) were
      identified from the THIN UK primary care database and grouped by insulin, detemir
      (n=165), glargine (n=1011) or NPH (n=420). Time from beginning insulin to the
      prescription of another insulin type or a glucagon-like peptide was compared
      between insulins in a Cox model adjusting for: demographics, HbA1c, history of
      vascular complications and cardiovascular risk factors. The strength of
      association between duration of use and these variables was investigated.
      RESULTS: The adjusted hazard ratios compared to glargine for treatment change
      were 1.58 (95% CI 1.25, 2.00) for detemir and 1.49 (1.25, 1.78) for NPH. Lower
      mean treatment HbA(1c) correlated with longer time to a different insulin regimen
      (Spearman rank correlation -0.30, p<0.01) as were continuing OGLDs, older age,
      longer time from diagnosis, lower body mass index, lower HbA(1c), and no heart
      failure at baseline. CONCLUSIONS: People who began treatment with glargine and
      those with better on-treatment HbA(1c) remained on their first insulin for longer
      than those who began detemir or NPH.

PMID- 21963106
TI  - HbA(1c) targets for type 2 diabetes: how many, ...how far!

PMID- 21963107
TI  - Specific cognitive abilities are associated with diabetes self-management
      behavior among patients with type 2 diabetes.
AB  - AIM: Patients with diabetes differ in compliance to diabetes self-management
      which influences their long-term health. Psychological factors, namely depression
      and cognitive abilities, are associated with diabetes self-management behavior.
      The aim of the study was to identify independent association of particular
      cognitive functions with diabetes self-management. METHODS: In a cross sectional
      study 98 adults with type 2 diabetes attending Diabetes Outpatient Clinic were
      examined using the measures of diabetes self-management (Summary of Diabetes Self
      Care Activities (SDSCA) measure), depression (Hamilton Depression Inventory
      (HDI)), diabetes distress (Problem Areas In Diabetes scale (PAID)), and the
      neuropsychological battery of tests for assessment of cognitive functions.
      Sociodemographic and diabetes-related data were collected. Univariate and
      multivariate regression analyses were used to identify and evaluate the
      predictors of diabetes self-management. RESULTS: Specific cognitive functions,
      namely immediate memory, visuospatial/constructional abilities, attention, and
      specific executive functions (planning and problem solving) were significantly
      associated with diabetes self-management. Among cognitive factors, planning and
      problem solving abilities were strongest predictors; furthermore, in a
      multivariate regression their association was independent from depression.
      CONCLUSIONS: Specific cognitive abilities, particularly planning and problem
      solving, play an independent role in diabetes self-management behaviors.
      Assessing patients' cognitive abilities may be of value for adjusting self
      management education and treatment regimen.

PMID- 21963108
TI  - Design and analysis of a model predictive controller for active queue management.
AB  - Model predictive (MP) control as a novel active queue management (AQM) algorithm
      in dynamic computer networks is proposed. According to the predicted future queue
      length in the data buffer, early packets at the router are dropped reasonably by
      the MPAQM controller so that the queue length reaches the desired value with
      minimal tracking error. The drop probability is obtained by optimizing the
      network performance. Further, randomized algorithms are applied to analyze the
      robustness of MPAQM successfully, and also to provide the stability domain of
      systems with uncertain network parameters. The performances of MPAQM are
      evaluated through a series of simulations in NS2. The simulation results show
      that the MPAQM algorithm outperforms RED, PI, and REM algorithms in terms of
      stability, disturbance rejection, and robustness.

PMID- 21963109
TI  - [Uterine arteriovenous malformations: diagnosis and treatment in 2011].
AB  - Uterine arteriovenous malformations (UAVM) are rare. They mostly occur after endo
      uterine trauma, or are less often congenital. When symptomatic, they may be a
      cause of uterine recurrent and massive bleeding. Diagnosis should be evoked in
      these cases, to avoid haemostatic curettage which will be useless and injurious.
      UAVM is often suspected by Doppler ultrasound, but pelvic MRI seems to be also
      relevant. Angiography confirms the diagnosis and allows concomitant embolization.
      Uterine embolization seems to be currently the best treatment, however surgery
      should still be performed in case of failure or hemodynamic instability. In this
      work, we aim to evaluate diagnosis and therapeutic modalities for UAVM.

PMID- 21963110
TI  - Acinetobacter community-acquired pneumonia in a healthy child.
AB  - Acinetobacter is involved in a variety of infectious diseases primarily
      associated with healthcare. Recently there has been increasing evidence of the
      important role these pathogens play in community acquired infections. We report
      on the case of a previously healthy child, aged 28 months, admitted for fever,
      cough and pain on the left side of the chest, which on radiographic examination
      corresponded to a lower lobe necrotizing pneumonia. After detailed diagnostic
      work-up, community acquired Acinetobacter lwoffii pneumonia was diagnosed. The
      child had frequently shared respiratory equipment with elderly relatives with
      chronic obstructive pulmonary disease. As there were no other apparent risk
      factors, it could be assumed that the sharing of the equipment was the source of
      infection. The authors wish to draw attention to this possibility, that a
      necrotising community-acquired pneumonia due to Acinetobacter lwoffii can occur
      in a previously healthy child and to the dangers of inappropriate use and poor
      sterilisation of nebulisers. This case is a warning of the dangers that these
      bacteria may pose in the future in a community setting.

PMID- 21963111
TI  - A conserved regulatory role for antisense RNA in meiotic gene expression in
      yeast.
AB  - A significant fraction of the eukaryotic genome is transcribed into RNAs that do
      not encode proteins, termed non-coding RNA (ncRNA). One class of ncRNA that is of
      particular interest is antisense RNAs, which are complementary to protein coding
      transcripts (mRNAs). In this article, we summarize recent studies using different
      yeasts that reveal a conserved pattern in which meiotically expressed genes have
      antisense transcripts in vegetative cells. These antisense transcripts repress
      the basal transcription of the mRNA during vegetative growth and are diminished
      as cells enter meiosis. While the mechanism(s) by which these antisense RNAs
      interfere with production of sense transcripts is not yet understood, the effects
      appear to be independent of the canonical RNAi machinery.

PMID- 21963112
TI  - ParA ATPases can move and position DNA and subcellular structures.
AB  - Prokaryotic chromosomes and plasmids can be actively segregated by partitioning
      (par) loci. The common ParA-encoding par loci segregate plasmids by arranging
      them in regular arrays over the nucleoid by an unknown mechanism. Recent
      observations indicate that ParA moves plasmids and chromosomes by a pulling
      mechanism. Even though ParAs form filaments in vitro it is not known whether
      similar structures are present in vivo. ParA of P1 forms filaments in vitro at
      very high concentrations only and filament-like structures have not been observed
      in vivo. Consequently, a 'diffusion-ratchet' mechanism was suggested to explain
      plasmid movement by ParA of P1. We compare this mechanism with our previously
      proposed filament model for plasmid movement by ParA. Remarkably, ParA homologues
      have been discovered to arrange subcellular structures such as carboxysomes and
      chemotaxis sensory receptors in a regular manner very similar to those of the
      plasmid arrays.

PMID- 21963113
TI  - Static and dynamic pressure prediction for prosthetic socket fitting assessment
      utilising an inverse problem approach.
AB  - OBJECTIVE: It has been recognised in a review of the developments of lower-limb
      prosthetic socket fitting processes that the future demands new tools to aid in
      socket fitting. This paper presents the results of research to design and
      clinically test an artificial intelligence approach, specifically inverse problem
      analysis, for the determination of the pressures at the limb/prosthetic socket
      interface during stance and ambulation. METHODS: Inverse problem analysis is
      based on accurately calculating the external loads or boundary conditions that
      can generate a known amount of strain, stresses or displacements at pre
      determined locations on a structure. In this study a backpropagation artificial
      neural network (ANN) is designed and validated to predict the interfacial
      pressures at the residual limb/socket interface from strain data collected from
      the socket surface. The subject of this investigation was a 45-year-old male
      unilateral trans-tibial (below-knee) traumatic amputee who had been using a
      prosthesis for 22 years. RESULTS: When comparing the ANN predicted interfacial
      pressure on 16 patches within the socket with actual pressures applied to the
      socket there is shown to be 8.7% difference, validating the methodology.
      Investigation of varying axial load through the subject's prosthesis, alignment
      of the subject's prosthesis, and pressure at the limb/socket interface during
      walking demonstrates that the validated ANN is able to give an accurate full
      field study of the static and dynamic interfacial pressure distribution.
      CONCLUSIONS: To conclude, a methodology has been developed that enables a
      prosthetist to quantitatively analyse the distribution of pressures within the
      prosthetic socket in a clinical environment. This will aid in facilitating the
      "right first time" approach to socket fitting which will benefit both the patient
      in terms of comfort and the prosthetist, by reducing the time and associated
      costs of providing a high level of socket fit.

PMID- 21963114
TI  - New 5-benzylidenethiazolidin-4-one inhibitors of bacterial MurD ligase: design,
      synthesis, crystal structures, and biological evaluation.
AB  - Mur ligases (MurC-MurF), a group of bacterial enzymes that catalyze four
      consecutive steps in the formation of cytoplasmic peptidoglycan precursor, are
      becoming increasingly adopted as targets in antibacterial drug design. Based on
      the crystal structure of MurD cocrystallized with thiazolidine-2,4-dione
      inhibitor I, we have designed, synthesized, and evaluated a series of improved
      glutamic acid containing 5-benzylidenerhodanine and 5-benzylidenethiazolidine-2,4
      dione inhibitors of MurD with IC(50) values up to 28 MUM. Inhibitor 37, with an
      IC(50) of 34 MUM, displays a weak antibacterial activity against S. aureus ATCC
      29213 and E. faecalis ATCC 29212 with minimal inhibitory concentrations of 128
      MUg/mL. High-resolution crystal structures of MurD in complex with two new
      inhibitors (compounds 23 and 51) reveal details of their binding modes within the
      active site and provide valuable information for further structure-based
      optimization.

PMID- 21963115
TI  - Oligopeptide cyclophilin inhibitors: a reassessment.
AB  - Potent cyclophilin A (CypA) inhibitors such as non-immunosuppressive cyclosporin
      A (CsA) derivatives have been already used in clinical trials in patients with
      viral infections. CypA is a peptidyl prolyl cis/trans isomerase (PPIase) that
      catalyzes slow prolyl bond cis/trans interconversions of the backbone of
      substrate peptides and proteins. In this study we investigate whether the
      notoriously low affinity inhibitory interaction of linear proline-containing
      peptides with the active site of CypA can be increased through a combination of a
      high cis/trans ratio and a negatively charged C-terminus as has been recently
      reported for Trp-Gly-Pro. Surprisingly, isothermal titration calorimetry did not
      reveal formation of an inhibitory CypA/Trp-Gly-Pro complex previously described
      within a complex stability range similar to CsA, a nanomolar CypA inhibitor.
      Moreover, despite of cis content of 41% at pH 7.5 Trp-Gly-Pro cannot inhibit CypA
      catalyzed standard substrate isomerization up to high micromolar concentrations.
      However, in the context of the CsA framework a net charge of -7 clustered at the
      amino acid side chain of position 1 resulted in slightly improved CypA
      inhibition.

PMID- 21963117
TI  - A rising prevalence of advanced cancer. Foreword.

PMID- 21963116
TI  - Synthesis and anticonvulsant activity of some new thiazolo[3,2-a][1,3]diazepine,
      benzo[d]thiazolo[5,2-a][12,6]diazepine and benzo[d]oxazolo[5,2-a][12,6]diazepine
      analogues.
AB  - A new series of 6,7-dihydro-thiazolo[3,2-a][1,3]diazepines (9-12),
      benzo[d]thiazolo[5,2-a][12,6]diazepines (19-21) and benzo[d]oxazolo[5,2
      a][12,6]diazepine (24) analogues were synthesized and evaluated for their
      anticonvulsant activity. Compounds (E)-2-bromo-6,7-dihydro-thiazolo[3,2
      a][1,3]diazepine-8(5H)-thione (12), 3-chloro-benzo[d]thiazolo[5,2
      a][12,6]diazepin-10-one (20), and 4-chloro-benzo[d]oxazolo[5,2-a][12,6] diazepin
      10-one (24) showed 100% protection against PTZ- and bicuculline-induced seizures;
      70%, 33%, 70% protection against MES-induced tonic extension; and 70%, 66%, 100%
      protection against picrotoxin-induced convulsions, respectively. Compounds 12,
      20, and 24 proved to act as GABA(A) receptor agonists, with ED(50) values of 252,
      380, 251 mg/kg; TD(50) values of 398, 417, 355 mg/kg; PI values of 1.58, 1.09,
      1.41; LD(50) values of 380, 617, 537 mg/kg and TI values of 1.51, 1.62, 2.14,
      respectively.

PMID- 21963119
TI  - The PRISMA Symposium 3: lessons from beyond Europe. why invest in research and
      service development in palliative care? An Australian perspective.
AB  - Hospice and palliative care services need to be able to compete with finite
      health care resources. To compete for such funding, the sector needs to
      continuously improve the evidence base that demonstrates improved outcomes, or
      else funding will continue to be at the level of a "social good" rather than as
      services that deliver improved health outcomes. Three questions need to be
      answered for policy makers and health funders: 1) Why invest health care spending
      in hospice and palliative care?, 2) Why invest research monies in hospice and
      palliative care clinical research and health service development?, and 3) How can
      emerging evidence be more effectively implemented to improve patient outcomes? No
      single measure captures the net benefit of hospice and palliative care services.
      By patient-defined parameters, hospice and palliative care services have
      demonstrated benefits, including physical symptom control. To meet patients'
      concerns, greater emphasis needs to be placed on maintaining physical
      independence for a longer period of time. Targeted investment of research funding
      can deliver further improvements in patient outcomes and models of service
      delivery. Rigorous studies are feasible and necessary if each patient is going to
      receive the best possible support. Benchmarking and service development
      strategies can deliver improved patient outcomes. With routine point-of-care data
      collection and feedback loops to individual services, patient-valued outcomes and
      resourcing can be improved in hospice and palliative care. Public-good
      investments in hospice and palliative care research are vital to building the
      evidence base for improving the quality of care offered.

PMID- 21963118
TI  - The PRISMA Symposium 1: outcome tool use. Disharmony in European outcomes
      research for palliative and advanced disease care: too many tools in practice.
AB  - CONTEXT: As the European population ages and the number of cancer deaths annually
      increases, there is an urgent requirement to provide high-quality, effective
      care. The measurement of outcomes in advanced disease is complex, and to conduct
      comparative research and meta-analyses, appropriate tool selection is essential.
      OBJECTIVES: This study aimed to identify the outcome tools currently in use in
      end-of-life care (both clinically and for research) across Europe and investigate
      the preferred features of outcome tools from the perspective of those who select
      and apply them. METHODS: A pan-European Internet-based survey of tool users was
      conducted in research and clinical populations. Respondents were asked to
      identify the tools they are using and describe ideal features of the measures.
      The study was conducted in accordance with guidance for best practice in web
      based research. RESULTS: Of the 311 participants who completed a survey, 99 tools
      in clinical care and audit, and 94 in research, were cited by less than 10
      participants. Further data revealed that respondents require the number of
      potential tools to be rationalized and that brief tools are favored. CONCLUSION:
      The selection of valid and appropriate tools for palliative care populations
      requires expert guidance and support to ensure that clinicians and researchers
      are collecting data that have validity and potential for comparison within and
      between populations and countries.

PMID- 21963120
TI  - The PRISMA Symposium 4: how should Europe progress end-of-life and palliative
      clinical care research? Recommendations from the proceedings.
AB  - Within aging European populations, the need to progress end-of-life and
      palliative care policy is becoming increasingly important. PRISMA, a European
      Commission-funded project, aimed to identify and coordinate research priorities,
      measurement, and practice in end-of-life care for Europe. PRISMA conducted a
      three-year multidisciplinary program to advance science and policy and to enhance
      coordination of cross-national activity. The final PRISMA symposium was convened
      to disseminate our new knowledge and activities and was held for European Union
      level and national-level policy makers, policy influencers, and funders. Nearly
      100 international invited delegates participated in the symposium, with the
      understanding that European research is aided by international partnerships and
      the free exchange of ideas and resources across states. The series of invited
      speakers, roundtables, and floor discussions underlined the necessity for
      clinical and public priorities to inform holistic outcome measurement research
      supported by government action informed by policy. Sustainable leadership, clear
      terminology and pan-European collaborative networks, and protected research
      funding designated for end-of-life or palliative care were identified as
      essential to progress end-of-life and palliative care research and innovation in
      Europe. An agreed set of outcome measures for end-of-life and palliative care
      that builds on previous pan-European projects is fundamental to a cross-national
      program of development in order to advance research and innovation within Europe.

PMID- 21963121
TI  - Current trends in venous thromboembolism among persons hospitalized with acute
      traumatic spinal cord injury: does early access to rehabilitation matter?
AB  - OBJECTIVE: To determine the incidence of venous thromboembolism (VTE) among
      patients with traumatic spinal cord injury (TSCI) in acute care settings that is
      attributable to extended length of stay (LOS), insurance status, and access to
      rehabilitation. DESIGN: Population-based, retrospective cohort study. SETTING:
      Levels I through III and undesignated trauma centers. PARTICIPANTS: Patients with
      acute TSCI (N=3389) discharged from all acute care hospitals in South Carolina
      from 1998 through 2009, and a representative sample of patients with TSCI (n=186)
      interviewed 1 year later. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE:
      VTE while in acute care. RESULTS: Annual incidence of TSCI is 67.2 per million in
      the state of South Carolina, while the cumulative incidence of VTE is 4.1%.
      Patients with TSCI who developed VTE were nearly 4 times more likely (odds ratio
      [OR], 3.98; 95% confidence interval [CI], 2.57-6.17) to have been those who
      stayed 12 days or longer in acute care after adjusting for covariates. The
      adjusted mean LOS in acute care was 32.0 days (95% CI, 27.7-37.2) for patients
      with TSCI who had indigent insurance versus 11.3 days (95% CI, 4.9-17.6) for
      Medicare, and 18.5 days (95% CI, 14.5-22.5) for commercial insurance after
      adjusting for VTE, disposition, and year of discharge. Only 20% of the persons
      under indigent care received rehabilitation from accredited rehabilitation
      facilities in contrast to 60% under commercial insurance. CONCLUSIONS: Fewer
      patients with TSCI under indigent care received postacute rehabilitation compared
      with Medicare or commercial insurance. Insurance status remains a major barrier
      to timely transfer to rehabilitation, leading to protracted LOS in acute care
      with increased risk of VTE.

PMID- 21963122
TI  - Scheduled telephone intervention for traumatic brain injury: a multicenter
      randomized controlled trial.
AB  - OBJECTIVE: To evaluate the effect of a Scheduled Telephone Intervention (STI)
      compared with usual care (UC) on function, health/emotional status,
      community/work activities, and well-being at 1 and 2 years after traumatic brain
      injury (TBI). DESIGN: Two group, randomized controlled trial. SETTING: Telephone
      contacts with subjects recruited in inpatient rehabilitation. PARTICIPANTS:
      Eligible subjects (N=433) with TBI (age>16y) were randomly assigned to STI plus
      UC (n=210) or UC (n=223) at discharge. STI subjects (n=169) completed the outcome
      at year 1 (118 at year 2) and 174 UC subjects at year 1 (123 at year 2).
      INTERVENTIONS: STI subjects received calls at 2 and 4 weeks and 2, 3, 5, 7, 9,
      12, 15, 18, and 21 months consisting of brief training in problem solving,
      education, or referral. MAIN OUTCOME MEASURES: A composite outcome at 1 year was
      the primary endpoint. Analysis on intent-to-treat basis used linear regression
      adjusted for site, Glasgow Coma Scale, race/ethnicity, age, FIM, sex, and
      Disability Rating Scale (DRS). Secondary analyses were conducted on individual
      and composite measures (FIM, DRS, community participation indicators, Glasgow
      Outcome Scale [Extended], Short Form-12 Health Survey, Brief Symptom Inventory
      18, EuroQOL, and modified Perceived Quality of Life). RESULTS: No significant
      differences were noted between the groups at years 1 or 2 for primary (P=.987
      regression for year 1, P=.983 for year 2) or secondary analyses. CONCLUSIONS:
      This study failed to replicate the findings of a previous single center study of
      telephone-based counseling. While telephone mediated treatment has shown promise
      in other studies, this model of flexible counseling in problem solving and
      education for varied problems was not effective over and above usual care.

PMID- 21963123
TI  - A multidimensional computer adaptive test approach to dyspnea assessment.
AB  - OBJECTIVES: To develop and test a prototype dyspnea computer adaptive test (CAT).
      DESIGN: Prospective study. SETTING: Two outpatient medical facilities.
      PARTICIPANTS: A convenience sample of adults (N=292) with chronic obstructive
      pulmonary disease (COPD). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: We
      developed a modified and expanded item bank and CAT for the Dyspnea Management
      Questionnaire (DMQ), an outcome measure consisting of 4 dyspnea dimensions:
      dyspnea intensity, dyspnea anxiety, activity avoidance, and activity self
      efficacy. RESULTS: Factor analyses supported a 4-dimensional model underlying the
      71 DMQ items. The DMQ item bank achieved acceptable Rasch model fit statistics,
      good measurement breadth with minimal floor and ceiling effects, and evidence of
      high internal consistency reliability (alpha=.92-.98). With the use of CAT
      simulation analyses, the DMQ-CAT showed high measurement accuracy compared with
      the total item pool (r=.83-.97, P<.0001) and evidence of good to excellent
      concurrent validity (r=-.61 to -.80, P<.0001). All DMQ-CAT domains showed
      evidence for known-groups validity (P<=.001). CONCLUSIONS: The DMQ-CAT reliably
      and validly captured 4 distinct dyspnea domains. Multidimensional dyspnea
      assessment in COPD is needed to better measure the effectiveness of
      pharmacologic, pulmonary rehabilitation, and psychosocial interventions in not
      only alleviating the somatic sensation of dyspnea but also reducing dysfunctional
      emotions, cognitions, and behaviors associated with dyspnea, especially for
      anxious patients.

PMID- 21963124
TI  - Vacuum-assisted socket suspension compared with pin suspension for lower
      extremity amputees: effect on fit, activity, and limb volume.
AB  - OBJECTIVE: To investigate the effect of a vacuum-assisted socket suspension
      system as compared with pin suspension on lower extremity amputees. DESIGN:
      Randomized crossover with 3-week acclimation. SETTING: Household, community, and
      laboratory environments. PARTICIPANTS: Unilateral, transtibial amputees (N=20
      enrolled, N=5 completed). INTERVENTIONS: (1) Total surface-bearing socket with a
      vacuum-assisted suspension system (VASS), and (2) modified patellar tendon
      bearing socket with a pin lock suspension system. MAIN OUTCOME MEASURES: Activity
      level, residual limb volume before and after a 30-minute treadmill walk, residual
      limb pistoning, and Prosthesis Evaluation Questionnaire. RESULTS: Activity levels
      were significantly lower while wearing the vacuum-assisted socket suspension
      system than the pin suspension (P=.0056; 38,000 +/- 9,000 steps per 2 wk vs
      73,000 +/- 18,000 steps per 2 wk, respectively). Residual limb pistoning was
      significantly less while wearing the vacuum-assisted socket suspension system
      than the pin suspension (P=.0021; 1 +/- 3mm vs 6 +/- 4mm, respectively).
      Treadmill walking had no effect on residual limb volume. In general, participants
      ranked their residual limb health higher, were less frustrated, and claimed it
      was easier to ambulate while wearing a pin suspension compared with the VASS.
      CONCLUSIONS: The VASS resulted in a better fitting socket as measured by limb
      movement relative to the prosthetic socket (pistoning), although the clinical
      relevance of the small but statistically significant difference is difficult to
      discern. Treadmill walking had no effect, suggesting that a skilled prosthetist
      can control for daily limb volume fluctuations by using conventional, nonvacuum
      systems. Participants took approximately half as many steps while wearing the
      VASS which, when coupled with their subjective responses, suggests a preference
      for the pin suspension system.

PMID- 21963125
TI  - Evaluation of a peer-led falls prevention program for older adults.
AB  - OBJECTIVE: To evaluate measures of strength and balance and falls incidence in
      participants attending fall prevention exercise classes taught by volunteer peer
      leaders, paid professional (Age Concern Otago group), or a comparison class
      (comparison group). DESIGN: Quasi-experimental evaluation with 12-month follow
      up. SETTING: Community. PARTICIPANTS: Older adults with increased fall risk
      (N=118; mean age, 75.5 y; age range, 65-94 y), with 23% drop out at 12 months.
      INTERVENTION: Peer-led group (n=52) and Age Concern Otago (n=41) weekly 1-hour
      strength and balance classes adapted from a home-based nurse/physical therapist
      administered program and comparison group (n=25) 1-hour weekly seated exercise
      classes. MAIN OUTCOME MEASURES: Timed Up and Go test, 30-second chair stand,
      functional reach, step touch, Single Leg Stand, and balance confidence at
      baseline, 10 weeks, and 6 and 12 months. Falls diaries collected monthly for 12
      months. Continued exercise participation questionnaire at 6 and 12 months.
      RESULTS: At baseline, the peer-led group achieved normative standards on most
      tests and performed significantly better than the Age Concern Otago and
      comparison groups (overall P<.05). The Age Concern Otago group reached normative
      standards on most tests at 10 weeks. Functional improvements were similar in the
      peer-led group and Age Concern Otago groups from 10 weeks to 12 months, and all
      functional measures were significantly greater than in the comparison group
      (overall P<.02). Poisson regression showed a tendency for a 27% decrease in falls
      for the peer-led group compared with the comparison group (incidence rate ratio
      [IRR], .73; 95% confidence interval, .48-1.1; P=.07). Continued participation in
      strength and balance classes at 12 months was greater in the peer-led group and
      Age Concern Otago groups compared with the comparison group. CONCLUSIONS: This
      peer-led model maintained measures of strength and balance and was superior to
      seated exercise. People in the Age Concern Otago group chose to continue these
      classes over other activities, whereas the comparison group had discontinued
      exercise classes by 12 months. Peer-led classes may decrease the fall incidence,
      although larger studies are needed to confirm this finding.

PMID- 21963126
TI  - Effects of treadmill inclination on the gait of individuals with chronic
      hemiparesis.
AB  - OBJECTIVE: To analyze the effects of electric treadmill inclination on the gait
      of individuals with chronic hemiparesis. DESIGN: Descriptive, observational
      study. SETTING: Laboratory for human movement analyses of UFRN. PARTICIPANTS:
      Individuals (N=18) with a mean age of 55.3 +/- 9.3 years and a lesion time of 36
      +/- 22.8 months. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Subjects
      were assessed for functional independence (FIM) and balance (Berg Balance Scale).
      Spatial-temporal variables were observed as well as the angular variation of the
      hip, knee, and ankle in the sagittal plane, while the individuals walked on the
      treadmill at 3 different inclinations (0%, 5%, and 10%). RESULTS: There was an
      increase in stance time between 0% and 5% (0.83 +/- 0.21 vs 0.87 +/- 0.20;
      P=.011) and 0% and 10% (0.83 +/- 0.21 vs 0.88 +/- 0.23; P=.021). The other
      spatial-temporal variables did not change. During initial contact there was an
      increase in the hip, knee, and ankle flexion angle. An increase in hip amplitude
      was also observed between 0% and 10% (37.83 +/- 5.23 vs 41.12 +/- 5.63; P<.001)
      and 5% and 10% (38.80 +/- 5.96 vs 41.12 +/- 5.63; P=.002) and in knee amplitude
      between 0% and 10% (47.51 +/- 15.07 vs 50.30 +/- 12.82; P=.040), as well as
      decreased hip extension and increased dorsiflexion. CONCLUSIONS: Treadmill
      inclination promoted angular alterations such as an increase in hip, knee, and
      ankle angle during initial contact and the swing phase and an increase in the
      amplitude of movement of the hip and knee, as well as an increase in stance time
      of the paretic lower limb.

PMID- 21963127
TI  - Biochemical markers of bone turnover in tibia fracture patients randomly assigned
      to growth hormone (GH) or placebo injections: Implications for detection of GH
      abuse.
AB  - CONTEXT: It has been argued that increased levels of bone remodelling markers are
      not suitable indicators of GH abuse, as bone injuries per se increase the
      expression levels of these markers. OBJECTIVE: To investigate the impact of a
      recovering tibia fracture on circulating bone markers in subjects receiving
      placebo or GH treatment. DESIGN AND SETTING: A randomised, double-blind, placebo
      controlled trial of up to 16weeks GH treatment, followed by a 16-week washout.
      PARTICIPANTS AND INTERVENTION: Subjects (406 adult males and females) with a
      tibia fracture were randomly allocated within three days after surgery, to either
      placebo or GH treatment (15, 30 or 60MUg/kg daily) until fracture healing or
      16weeks after treatment initiation. MAIN OUTCOME MEASURES: IGF-I, serum C
      terminal telopeptide of type I collagen (CTX), osteocalcin (OST) and bone
      specific alkaline phosphatase (BAP) were measured during and after treatment.
      RESULTS: Dose-dependent increases were observed in groups receiving GH, and mean
      levels in the highest GH dose group peaked at eight (IGF-I, CTX) or 12weeks (OST)
      after treatment initiation. Statistically significant differences between GH
      treatment and placebo were seen for IGF-I, CTX and OST in all GH dose groups
      throughout the treatment period, and persisted until eight (CTX) or 12 (OST)
      weeks after cessation of treatment. CONCLUSION: IGF-I, CTX and OST are suitable
      candidate markers of prolonged, illicit administration of GH. Furthermore, CTX
      and OST have potentials to serve as markers also after cessation of GH
      administration.

PMID- 21963128
TI  - Dehiscence of the third portion of the facial nerve.

PMID- 21963129
TI  - Recurrent meningitis associated with Duane syndrome type I.
AB  - We present the case of a 17-month-old male patient with a bilateral Duane
      syndrome type 1 associated to unilateral cochleovestibular dysplasia,
      perilymphatic fistula and recurrent meningitis. Diagnosis was carried out by MRI
      and CT scan. His management and treatment are described, as well as the
      postoperative evolution. We believe this is an exceptional case due to the low
      frequency of this syndrome, as well as to the otoneurological complications.

PMID- 21963130
TI  - Antimicrobial activities of sesquiterpene lactones and inositol derivatives from
      Hymenoxys robusta.
AB  - Six compounds from the aerial parts of the Argentinean plant Hymenoxys robusta
      (Rusby) Parker were isolated and their structures elucidated using extensive
      spectroscopic analyses. These compounds comprise two inositol derivatives and
      four 3,4-seco-pseudoguaianolides, including vermeerin. Bioactivity assays of
      these compounds against bacterial and fungal pathogens showed that only vermeerin
      possessed antimicrobial activity specific against Staphylococcus aureus, and
      showed no toxicity when exposed to human-derived macrophages.

PMID- 21963131
TI  - Live transgenic reporters of the vertebrate embryo's Segmentation Clock.
AB  - Imaging rapidly changing gene expression during embryogenesis is a challenge for
      the development of probes and imaging techniques. The vertebrate Segmentation
      Clock is a genetic network that controls the subdivision of the elongating
      embryonic body axis into somites, the precursors of adult segmented structures,
      such as vertebrae. Because of its rapid oscillations, direct observation of gene
      expression in this system has proven difficult, and so is a benchmark for
      transgene design and imaging in vivo. Transgenic approaches using destabilized
      reporter cassettes in the mouse embryo have provided the first glimpses of this
      dynamic expression system. Nevertheless, improvements in temporal and spatial
      resolution, paired with the ability to make precise quantifications, will be
      necessary to connect observations and theory.

PMID- 21963132
TI  - Whole-animal imaging, gene function, and the Zebrafish Phenome Project.
AB  - Imaging can potentially make a major contribution to the Zebrafish Phenome
      Project, which will probe the functions of vertebrate genes through the
      generation and phenotyping of mutants. Imaging of whole animals at different
      developmental stages through adulthood will be used to infer biological function.
      Cell resolutions will be required to identify cellular mechanism and to detect a
      full range of organ effects. Light-based imaging of live zebrafish embryos is
      practical only up to ~2 days of development, owing to increasing pigmentation and
      diminishing tissue lucency with age. The small size of the zebrafish makes
      possible whole-animal imaging at cell resolutions by histology and micron-scale
      tomography (microCT). The histological study of larvae is facilitated by the use
      of arrays, and histology's standard use in the study of human disease enhances
      its translational value. Synchrotron microCT with X-rays of moderate energy (10
      25 keV) is unimpeded by pigmentation or the tissue thicknesses encountered in
      zebrafish of larval stages and beyond, and is well-suited to detecting phenotypes
      that may require 3D modeling. The throughput required for this project will
      require robotic sample preparation and loading, increases in the dimensions and
      sensitivity of scintillator and CCD chips, increases in computer power, and the
      development of new approaches to image processing, segmentation, and
      quantification.

PMID- 21963134
TI  - Condition Yellow: a hospital-wide approach to ED overcrowding.

PMID- 21963133
TI  - Seeing elegance in gene regulatory networks of the worm.
AB  - There has been a recent explosion in the wealth of genomic data available to C.
      elegans researchers, as efforts to characterize gene expression and its
      regulators at a molecular level have borne significant fruit. Detailed
      measurement of gene expression at a variety of developmental stages, and in
      numerous individual tissues, has dramatically increased our understanding of cell
      type-specific gene expression networks. Characterization of the targets of
      transcription factors, chromatin-binding proteins, and miRNAs has provided genome
      wide insights into the mechanisms governing gene expression. Development of new
      techniques have allowed this characterization to begin to shift from whole
      organism studies to tissue-level, and even single-cell-level profiling, creating
      a first glimpse into gene regulatory circuits at the single-cell level in a
      living organism. Integration of these datasets has yielded novel insights into
      evolution, gene expression regulation, and the link between sequence and
      phenotype.

PMID- 21963135
TI  - Managing hemorrhagic shock in trauma: are we still drowning patients in the
      field?

PMID- 21963137
TI  - Taking care of children: the case for booster seats.

PMID- 21963136
TI  - A simulation study to improve quality of care in the emergency department of a
      community hospital.
AB  - In this article, a computer simulation study to improve the quality of care at
      the emergency department at a community hospital in Lexington, Kentucky, is
      presented. The simulation model is capable of evaluating the quality of care in
      terms of length of stay, waiting times, and patient elopement and has been
      validated by being compared with the data collected in the emergency department.
      Sensitivity analyses have been carried out to investigate the impact of workforce
      and diagnosis equipment on quality performance. The results suggest that, to
      ensure better clinical outcome, more nurses are needed; in addition, an
      additional computed tomography scanner is recommended. The model also shows that
      implementing team nursing policy (for 2 nurses) could lead to significant
      improvement in the emergency department's quality of care. Such a model provides
      a quantitative tool for continuous improvement and flow control in the emergency
      department and is also applicable to other departments in the hospital.

PMID- 21963139
TI  - Emergency nurse perceptions of individual and facility emergency preparedness.
AB  - INTRODUCTION: Disasters of any variety can occur at any given moment. Emergency
      departments are at the forefront of the response system, serving as the gateway
      to the most appropriate care of victims. The intent of the survey described in
      this article was to assess nurses' perception of their role in a disaster and
      their perceived susceptibility to a disaster. In addition, basic knowledge and
      role preparation was reviewed. METHODS: A descriptive survey using survey
      methodology was utilized. The 56-question survey, including 16 demographic
      questions, was developed for the purpose of this study. RESULTS: The results
      reflect that many emergency nurses have not taken basic actions to prepare
      themselves for a disaster, either personally or professionally. DISCUSSION: This
      article highlights the importance of disaster education geared to the needs of
      the emergency nurse.

PMID- 21963140
TI  - Spectroscopic and thermodynamic features of conical bubble luminescence.
AB  - The influence on luminescence from conical bubble collapse (CBL) with varying Ar
      gas content while perturbing the liquid 1,2-Propanediol (PD) has been
      investigated. The temporal, spatial, and spectral features were analysed with
      regards to the dynamics of collapse and liquid degradation. Sulphuric acid and
      sodium chloride were added to disturb the liquid. The following three cases were
      studied: PD/Ar, (I), (PD + H(2)SO(4))/Ar, (II), and (PD + H(2)SO(4) + NaCl)/Ar,
      (III). The intensities of those cases decrease as III > II > I. Temporally,
      single and multiple light emissions were found to occur. The pulse shape
      exhibited a large variety of profiles with a main maximum and up to two local
      maxima around the main maximum. These local maxima resembled those generated by
      laser cavitation. Spatially, no radial symmetry was detected in the light
      emissions. Spectrally, the Swan, CH and CN lines were observed at low volumes of
      gas and driving pressure. The .OH radical and OH-Ar bands, as well as the Na and
      K lines, consistently appeared superimposed on an underlying continuum that
      almost disappeared in (III). The Na line was observed with two satellite diffuse
      bands representing Na-Ar complexes in (I) and (II), whereas in (III), only the
      line of sodium could be seen. Weak and diffuse emission lines from the Ar atom in
      the near-IR region were observed in (I) and (II). The proposed mechanism of
      bright CBL was based on the energy transfer from electron-excited homolytic
      cleavage products to the chromophore molecules generated during the collapse
      rebound time line (~8200 K and ~1 ms of collapse time from model), which had
      accumulated inside the liquid and remained on the walls of cavity during the
      repetition of the collapse. A general mechanism for the bright CBL is broached.

PMID- 21963141
TI  - Genetic variations in CYP17A1, CACNB2 and PLEKHA7 are associated with blood
      pressure and/or hypertension in She ethnic minority of China.
AB  - OBJECTIVES: Two large-scale genome-wide association studies (GWAs) have
      identified multiple variants associated with blood pressure (BP) or hypertension.
      The present study was to investigate whether some variations were associated with
      BP traits and hypertension or even prehypertension in adult She ethnic minority
      of China. METHODS: The population of the present study comprised 4460 (1979 males
      and 2481 females, respectively) unrelated she ethnic minority based on a cross
      sectional study from Ningde City in Fujian province of China. There were 1692
      hypertensives, 1600 prehypertensives and 1168 normotensive controls,
      respectively. We genotyped 7 variants in CYP17A1, PLEKHA7, CACNB2, ATP2B1, TBX3
      TBX5, CSK-ULK3 and SH2B3 reported by the previous GWAs on Europeans. All analyses
      were performed in an additive genetic model. RESULTS: As the minor allele of
      rs653178 in/near SH2B3 was very rare with the frequency of 0.018, we excluded
      this single nucleotide polymorphism (SNP) in the further analyses. Of the other 6
      loci, linear regression analyses revealed that rs11191548 in CYP17A1 and
      rs11014166 in CACNB2 were significantly associated with systolic BP (beta = 
      1.17, P = 0.002 and beta = -0.50, P = 0.006, respectively), while only SNP
      rs11191548 was significantly associated with diastolic BP (beta = -0.56, P=0.002)
      after adjusted by age, sex and BMI. Two variants in CACNB2 and PLEKHA7 were found
      to be significantly related to hypertension (odds ratios [OR] and (95% confidence
      interval [CI]): 0.79 (0.65-0.97) and 1.19 (1.01-1.41), respectively) in logistic
      regression analyses after adjusted by age, sex and BMI. In addition, we found
      that combined risk alleles of the 6 SNPs increased risk of hypertension in a
      stepwise fashion (P for trend < 0.001). However, none of the 6 SNPs was
      significantly associated with BMI or prehypertension status. While logistic
      analysis showed that subjects with cumulative risk alleles more than 9 had
      significantly higher risk for prehypertension (adjusted OR: 3.10, P < 0.001)
      compared with those with risk alleles less than 4. CONCLUSIONS: We replicated
      that variations in CYP17A1, CACNB2 and PLEKHA7 were related to BP traits and/or
      hypertension in She population. In addition, although we failed to observe single
      gene associated with prehypertension, we first found that conjoint effect of
      multiple risk alleles on BP might increase the risk of progressing to
      prehypertension.

PMID- 21963142
TI  - Fluorescence and image guided resection in high grade glioma.
AB  - The extent of resection in high grade glioma is increasingly been shown to
      positively effect survival. Nevertheless, heterogeneity and migratory behavior of
      glioma cells make gross total resection very challenging. Several techniques were
      used in order to improve the detection of residual tumor. Aim of this study was
      to analyze advantages and limitations of fluorescence and image guided resection.
      A multicentric prospective study was designed to evaluate the accuracy of each
      method. Furthermore, the role of 5-aminolevulinc acid and neuronavigation were
      reviewed. Twenty-three patients harboring suspected high grade glioma, amenable
      to complete resection, were enrolled. Fluorescence and image guides were used to
      perform surgery. Multiple samples were obtained from the resection cavity of each
      lesion according to 5-ALA staining positivity and boundaries as delineated by
      neuronavigation. All samples were analyzed by a pathologist blinded to the intra
      operative labeling. Decision-making based on fluorescence showed a sensitivity of
      91.1% and a specificity of 89.4% (p<0.001). On the other hand, the image-guided
      resection accuracy was low (sensitivity: 57.8%; specificity: 57.4%; p=0.346). We
      observed that the sensitivity of 5-ALA can be improved by the combined use of
      neuronavigation, but this leads to a significant reduction in specificity. Thus,
      the use of auxiliary techniques should always be subject to critical skills of
      the surgeon. We advocate a large-scale study to further improve the assessment of
      multimodal approaches.

PMID- 21963143
TI  - Coding or non-coding: Need they be exclusive?

PMID- 21963144
TI  - The double life of RNA.

PMID- 21963145
TI  - The body balance training effect on improvement of motor functions in paretic
      extremities in patients after stroke. A randomized, single blinded trial.
AB  - OBJECTIVE: Study evaluates movement selectivity improvement in hemiparetic post
      stroke patients after balance training. METHODS: Study included 26 patients and
      15 healthy subjects (control group C). Patients were divided into two groups with
      20-day balance training (A) and without (B). Normal standing weight distribution
      was expressed in percentages, center of feet pressure (COP) sway velocities were
      evaluated in anterior-posterior and medio-lateral (Y, X) directions for normal
      standing with eyes open and closed (EO, EC) and for tandem. Brunnstrom scale
      assessed movement selectivity. RESULTS: Weight distribution dissymmetry
      (Delta10%) was found. It was reduced (Delta2%) after training in group A. COP
      were higher for X direction (+/-6mm/s vs +/-12mm/s) in normal standing.
      Difference (+/-12mm/s) was found for Y in tandem. Brunnstrom score increased in
      group A from 0.3 to 0.6. It was negatively correlated with average COP for EO and
      EC in Y and X and for tandem in X. CONCLUSION: Training reduces weight-bearing
      dissymmetry and improves movement selectivity.

PMID- 21963146
TI  - [Strategy of postoperative rehabilitation after femoral neck fracture in elderly
      patients].
AB  - The femoral neck fracture in elderly patient is an entity that is within the
      scope of "disease causing a femoral neck fracture". The specific factors for
      successful management of these elderly patients are centered around patient's
      comorbidities, specific management in a clinical pathway, and more or less early
      rehabilitation after surgery. The type of fracture, surgery, specific treatment,
      early active recovery for the patients lying in bed after surgery optimize the
      functional outcome at mean term. The improvement of nutritional status,
      equilibrium for comorbidities and early rehabilitation with walking activities
      and physiotherapy significantly improve functional outcome at short and medium
      terms and postoperative mortality. The use of multimodal analgesia and regional
      analgesia primarily by perioperative continuous femoral nerve blocks also improve
      the medical prognosis and functional outcome of the patient.

PMID- 21963147
TI  - [Minimally invasive valvular procedures: it was deemed impossible but as they
      ignored it, they have done it].

PMID- 21963148
TI  - Enhancement of mesenchymal stem cell angiogenic capacity and stemness by a
      biomimetic hydrogel scaffold.
AB  - In this study, we examined the capacity of a biomimetic pullulan-collagen
      hydrogel to create a functional biomaterial-based stem cell niche for the
      delivery of mesenchymal stem cells (MSCs) into wounds. Murine bone marrow-derived
      MSCs were seeded into hydrogels and compared to MSCs grown in standard culture
      conditions. Hydrogels induced MSC secretion of angiogenic cytokines and
      expression of transcription factors associated with maintenance of pluripotency
      and self-renewal (Oct4, Sox2, Klf4) when compared to MSCs grown in standard
      conditions. An excisonal wound healing model was used to compare the ability of
      MSC-hydrogel constructs versus MSC injection alone to accelerate wound healing.
      Injection of MSCs did not significantly improve time to wound closure. In
      contrast, wounds treated with MSC-seeded hydrogels showed significantly
      accelerated healing and a return of skin appendages. Bioluminescence imaging and
      FACS analysis of luciferase+/GFP+ MSCs indicated that stem cells delivered within
      the hydrogel remained viable longer and demonstrated enhanced engraftment
      efficiency than those delivered via injection. Engrafted MSCs were found to
      differentiate into fibroblasts, pericytes and endothelial cells but did not
      contribute to the epidermis. Wounds treated with MSC-seeded hydrogels
      demonstrated significantly enhanced angiogenesis, which was associated with
      increased levels of VEGF and other angiogenic cytokines within the wounds. Our
      data suggest that biomimetic hydrogels provide a functional niche capable of
      augmenting MSC regenerative potential and enhancing wound healing.

PMID- 21963149
TI  - EGFR-specific PEGylated immunoliposomes for active siRNA delivery in
      hepatocellular carcinoma.
AB  - The development of immunoliposomes for systemic siRNA (small interfering RNA)
      delivery is highly desired. We reported previously the development of targeted
      LPD (liposome-polycation-DNA complex) conjugated with anti-EGFR (epidermal growth
      factor receptor) Fab' (TLPD-FCC) for siRNA delivery, which showed superior gene
      silencing activity in EGFR-overexpressing breast cancers. However, TLPD-FCC did
      not achieve satisfactory gene silencing activity in EGFR-overexpressing
      hepatocellular carcinoma (HCC). In this study, some modifications including
      increased antibody conjugation efficiency and reduced PEGylation degree were made
      to TLPD-FCC to increase gene silencing activity in HCC. The resultant optimized
      liposomes denoted as TLPD-FP75 efficiently bound and delivered to EGFR
      overexpressing HCC, resulting in enhanced gene silencing activity compared to
      untargeted LPD (NTLPD-FP75). Tissue distribution in vivo revealed that the
      accumulation of TLPD-FP75 was higher than NTLPD-FP75 in orthotopic HCC model of
      mice. The promoted uptake of TLPD-FP75 in HCC cells was confirmed by confocal
      microscopy. To investigate the in vivo gene silencing activity, we administered
      TLPD-FP75 by intravenous injections into mice bearing orthotopic HCC. The results
      showed TLPD-FP75 potently suppressed luciferase expression, while little
      silencing was observed in NTLPD-FP75. TLPD-FP75 was demonstrated to possess
      potent gene silencing activity in HCC and will potentially increase the
      feasibility of HCC gene therapy.

PMID- 21963151
TI  - A risk profile of elite Australian athletes who use illicit drugs.
AB  - Much of the literature investigating the relationship between sports
      participation and substance use has focused upon student populations, with little
      focus being given to athletes who participate at elite levels. Identifying why
      some athletes may be at a greater risk for substance use can help in the design
      and implementation of prevention initiatives. Data for the current study was from
      1684 self-complete surveys with elite Australian athletes. Eight percent (n=134)
      of the sample reported the use of at least one of the six illicit drugs under
      investigation (ecstasy, cannabis, cocaine, meth/amphetamine, ketamine and GHB) in
      the past year. Having been offered or having had the opportunity to use illicit
      drugs in the past year, knowing other athletes who use drugs and identifying as a
      'full-time athlete' were significant predictors of past-year illicit drug use,
      while having completed secondary education or a post-school qualification was
      associated with a lower likelihood of past-year illicit drug use. Athletes are
      part of a sportsnet that includes family, coaches, support staff and other
      athletes, and these relationships may encourage the use, supply and demand for
      drugs. The current findings suggest that relationships with some of those in the
      sportsnet may play an important role when understanding illicit drug use among
      elite athletes. As education appears to be associated with a lower likelihood of
      illicit drug use among this group, initiatives should encourage athletes to
      engage in off-field pursuits which may also help prepare them for life after
      sport.

PMID- 21963150
TI  - Active leukocyte detachment and apoptosis/necrosis on PEG hydrogels and the
      implication in the host inflammatory response.
AB  - Monocytes/Macrophages have long been recognized as key players in inflammation
      and wound healing and are often employed in vitro to gain an understanding of the
      inflammatory response to biomaterials. Previous work has demonstrated a drastic
      decrease in primary monocyte adherent density on biomaterial surfaces coupled
      with a change in monocyte behavior over time. However, the mechanism responsible
      for this decrease remains unclear. In this study, we explored active detachment
      and cellular death as possible regulating factors. Specifically, extracellular
      TNF-alpha and ROS production were analyzed as potential endogenous stimulators of
      cell death. MMPs, but not calpains, were found to play a key role in active
      monocyte detachment. Monocyte death was found to peak at 24 h and occur by both
      apoptosis and necrosis as opposed to polymorphonuclear leukocyte death which
      mainly occurred through apoptosis. Finally, TNF-alpha and ROS production were not
      found to have a causal relationship with monocyte death on TCPS or PEG surfaces.
      The occurrence of primary monocyte apoptosis/necrosis as well as active
      detachment from a material surface has implications not only in in vitro study,
      but also in the translation of the in vitro inflammatory response of these cells
      to in vivo applications.

PMID- 21963152
TI  - Effects of cigarette smoking status on delay discounting in schizophrenia and
      healthy controls.
AB  - BACKGROUND: Delay discounting is a measure of future-oriented decision-making and
      impulsivity. Cigarette smoking is associated with rapid discounting of the value
      of delayed outcomes. In schizophrenia, however, cigarette smoking improves
      certain neurocognitive impairments associated with the disorder which may explain
      the high smoking rates in this population. This study examined the relationship
      between cigarette smoking and delay discounting in schizophrenia and control
      participants. METHODS: A total of N=130 participants, including those with
      schizophrenia (n=68) and healthy controls (n=62) were assessed on the Kirby Delay
      Discounting Task and compared across smoking status (smokers; non-smokers) and
      smoking history (current, former; never smokers). RESULTS: Smokers exhibited
      higher discounting rates (i.e., were more impulsive) than non-smokers of the same
      diagnostic group. Current and former smokers with schizophrenia exhibited similar
      and significantly higher discounting rates than never smokers, suggesting that in
      schizophrenia delay discounting is a trait-dependent phenomenon independent of
      current cigarette smoking. Consistent with previous studies, there was a trend
      for higher discounting rates in control current smokers compared to control
      former and never smokers. CONCLUSIONS: Smokers with and without schizophrenia
      have higher rates of delay discounting than non-smokers. However, in
      schizophrenia, rapid delay discounting appears to be a trait associated with
      having ever been a smoker (i.e., current and former smoking).

PMID- 21963153
TI  - Multimorbidity and its measurement.
AB  - Multimorbidity is increasing in frequency. It can be quantitatively measured and
      is a major correlate of high use of health services resources of all types,
      especially over time. The ACG System for characterizing multimorbidity is the
      only widely used method that is based on combinations of different TYPES of
      diagnoses over time, rather than the presence or absence of particular conditions
      or numbers of conditions. It incorporates administrative data (as from claims
      forms or medical records) on all types of encounters and is not limited to
      diagnoses captured during hospitalizations or other places of encounter. It can
      be employed in any one or combination of analytic models, and can incorporate
      medication use if desired. It is being used in clinical care, management of
      health services resources, in health services research to control for degree of
      morbidity, and in understanding morbidity patterns over time. In addition to its
      research uses, it is being employed in many countries in various applications as
      a policy to better understand health needs of populations and tailor health
      services resources to health needs.

PMID- 21963154
TI  - A copper-hydrogen peroxide redox system induces dityrosine cross-links and
      chemokine oligomerisation.
AB  - The activity of the chemoattractant cytokines, the chemokines, in vivo is
      enhanced by oligomerisation and aggregation on glycosaminoglycan (GAG),
      particularly heparan sulphate, side chains of proteoglycans. The chemokine RANTES
      (CCL5) is a T-lymphocyte and monocyte chemoattractant, which has a minimum
      tetrameric structure for in vivo activity and a propensity to form higher order
      oligomers. RANTES is unusual among the chemokines in having five tyrosine
      residues, an amino acid susceptible to oxidative cross-linking. Using
      fluorescence emission spectroscopy, Western blot analysis and LCMS-MS, we show
      that a copper/H2O2 redox system induces the formation of covalent dityrosine
      cross-links and RANTES oligomerisation with the formation of tetramers, as well
      as higher order oligomers. Amongst the transition metals tested, namely copper,
      nickel, mercury, iron and zinc, copper appeared unique in this respect. At high
      (400 MUM) concentrations of H2O2, RANTES monomers, dimers and oligomers are
      destroyed, but heparan sulphate protects the chemokine from oxidative damage,
      promoting dityrosine cross-links and multimer formation under oxidative
      conditions. Low levels of dityrosine cross-links were detected in copper/H2O2
      treated IL-8 (CXCL8), which has one tyrosine residue, and none were detected in
      ENA-78 (CXCL5), which has none. Redox-treated RANTES was fully functional in
      Boyden chamber assays of T-cell migration and receptor usage on activated T-cells
      following RANTES oligomerisation was not altered. Our results point to a
      protective, anti-oxidant, role for heparan sulphate and a previously unrecognised
      role for copper in chemokine oligomerisation that may offer an explanation for
      the known anti-inflammatory effect of copper-chelators such as penicillamine and
      tobramycin.

PMID- 21963155
TI  - Primary human bone marrow adipocytes support TNF-alpha-induced osteoclast
      differentiation and function through RANKL expression.
AB  - PURPOSE: In previous reports, it was demonstrated that bone marrow adipocytes
      were related to steroid osteoporosis through osteoclastogenesis induced by
      Receptor Activator of Nuclear factor kappa-B Ligand (RANKL) expression. The
      purpose of this study was to evaluate the effect of Tumor necrosis factor-alpha
      (TNF-alpha) on RANKL expression in bone marrow adipocytes, and osteoclast
      differentiation supported by human bone marrow adipocytes. METHODS: RANKL,
      osteoprotegerin (OPG), and macrophage-colony stimulating factor (M-CSF) mRNA
      expression in bone marrow adipocytes and their regulation by TNF-alpha treatment
      were measured by real-time RT-PCR. Co-cultures of bone marrow adipocytes and
      osteoclast precursors were performed with or without TNF-alpha, and osteoclast
      differentiation was evaluated morphologically and functionally. RESULTS: RANKL
      expression and an increase in the RANKL/OPG ratio in bone marrow adipocytes were
      stimulated by TNF-alpha treatment. In co-culture of bone marrow adipocytes and
      osteoclast precursors with TNF-alpha, the number of TRAP-positive multinuclear
      cells and resorption cavity formations of calcium phosphate film were increased.
      Osteoclast differentiation was suppressed by anti-RANKL antibody treatment. In co
      culture with non-cell-contact conditions, no TRAP-positive cells or resorption
      cavity formations were observed. CONCLUSIONS: TNF-alpha increased RANKL
      expression in primary human bone marrow adipocytes. TNF-alpha induced the ability
      of bone marrow adipocytes to promote osteoclast differentiation and activity in a
      manner directly related to RANKL expression.

PMID- 21963156
TI  - The influence of scaffold elasticity on germ layer specification of human
      embryonic stem cells.
AB  - Mechanical forces are critical to embryogenesis, specifically, in the lineage
      specification gastrulation phase, whereupon the embryo is transformed from a
      simple spherical ball of cells to a multi-layered organism, containing properly
      organized endoderm, mesoderm, and ectoderm germ layers. Several reports have
      proposed that such directed and coordinated movements of large cell collectives
      are driven by cellular responses to cell deformations and cell-generated forces.
      To better understand these environmental-induced cell changes, we have modeled
      the germ layer formation process by culturing human embryonic stem cells (hESCs)
      on three dimensional (3D) scaffolds with stiffness engineered to model that found
      in specific germ layers. We show that differentiation to each germ layer was
      promoted by a different stiffness threshold of the scaffolds, reminiscent of the
      forces exerted during the gastrulation process. The overall results suggest that
      three dimensional (3D) scaffolds can recapitulate the mechanical stimuli required
      for directing hESC differentiation and that these stimuli can play a significant
      role in determining hESC fate.

PMID- 21963158
TI  - Fractures of the ulnar coronoid process.
AB  - The ulnar coronoid process plays a central role in elbow stability due to its
      unique anatomic characteristics. A fracture of the coronoid, although uncommon,
      represents a serious injury that can adversely affect functional outcome if not
      treated appropriately. Several surgical interventions addressing different
      fracture patterns are being increasingly recognised as effective treatment
      options even for smaller fragments. A review of the literature was performed in
      order to evaluate different treatment strategies applied to clearly defined
      fracture configurations. 14 articles reporting data for the management of 236
      coronoid fractures met our inclusion criteria and were subjected to critical
      analysis. The data suggest that recognition of specific coronoid fracture
      patterns, use of appropriate classification systems and application of staged
      surgical protocols can stabilise the elbow effectively and lead to favourable
      outcomes.

PMID- 21963157
TI  - Recombinant exon-encoded resilins for elastomeric biomaterials.
AB  - Resilin is an elastomeric protein found in specialized regions of the cuticle of
      most insects, providing outstanding material properties including high resilience
      and fatigue lifetime for insect flight and jumping needs. Two exons (1 and 3)
      from the resilin gene in Drosophila melanogaster were cloned and the encoded
      proteins expressed as soluble products in Escherichia coli. A heat and salt
      precipitation method was used for efficient purification of the recombinant
      proteins. The proteins were solution cast from water and formed into rubber-like
      biomaterials via horseradish peroxidase-mediated cross-linking. Comparative
      studies of the two proteins expressed from the two different exons were
      investigated by Fourier Transform Infrared Spectroscopy (FTIR) and Circular
      Dichrosim (CD) for structural features. Little structural organization was found,
      suggesting structural order was not induced by the enzyme-mediated di-tyrosine
      cross-links. Atomic Force Microscopy (AFM) was used to study the elastomeric
      properties of the uncross-linked and cross-linked proteins. The protein from exon
      1 exhibited 90% resilience in comparison to 63% for the protein from exon 3, and
      therefore may be the more critical domain for functional materials to mimic
      native resilin. Further, the cross-linking of the recombinant exon 1 via the
      citrate-modified photo-Fenton reaction was explored as an alternative di-tyrosine
      mediated polymerization method and resulted in both highly elastic and adhesive
      materials. The citrate-modified photo-Fenton system may be suitable for in vivo
      applications of resilin biomaterials.

PMID- 21963159
TI  - Letter from the editor: sarcomas.

PMID- 21963160
TI  - Imaging of thoracic sarcomas of the chest wall, pleura, and lung.
AB  - Primary sarcomas of the thorax are uncommon. The purpose of this review is to
      describe the radiologic findings of sarcomas affecting the thorax, in particular
      the chest wall, pleura, and lungs. Most primary sarcomas affecting the thorax
      arise in the chest wall, and the most common sarcomas of the chest wall are
      chondrosarcoma, osteosarcoma, Ewing's sarcoma/primitive neuroectodermal tumor,
      malignant fibrous histiocytoma, and fibrosarcoma. Primary pleural and pulmonary
      sarcomas are rare. Although histologic analysis is almost always required for
      accurate diagnosis, imaging is important for staging of these tumors, and several
      of these tumors have distinctive radiologic features, allowing the radiologist to
      narrow the differential diagnosis.

PMID- 21963161
TI  - Imaging sarcomas of the great vessels and heart.
AB  - Primary sarcomas of the aorta, pulmonary artery, superior vena cava, inferior
      vena cava, and the heart are rare neoplasms. Aortic sarcomas are broadly
      categorized as either primarily luminal or primarily mural, with luminal sarcomas
      more likely to be misdiagnosed as thrombus. Pulmonary artery sarcomas are often
      mistaken for pulmonary embolism both clinically and at imaging. Vena caval
      sarcomas appear as intraluminal or extraluminal masses connecting to or filling
      the veins. The most common are leiomyosarcomas of the inferior vena cava. Primary
      sarcomas of the heart are rare and usually appear as heterogeneous aggressive
      masses.

PMID- 21963162
TI  - Sarcomas of abdominal organs: computed tomography and magnetic resonance imaging
      findings.
AB  - Sarcomas originating from abdominal organs are extremely rare, and literature in
      which investigators focus on their imaging features is scarce. This article aims
      to review the computed tomography and magnetic resonance imaging features of
      these rare tumors and to help in clinical diagnosis. Various sarcomas (eg,
      angiosarcoma, undifferentiated embryonal sarcoma, leiomyosarcoma, carcinosarcoma,
      rhabdomyosarcoma) originating, respectively, from different abdominal visceral
      organs (liver, pancreas, spleen, kidney, adrenal gland, uterus, and prostate
      gland) are reviewed along with cases we encountered.

PMID- 21963163
TI  - Retroperitoneal sarcomas.
AB  - Retroperitoneal sarcomas are a rare and highly malignant group of tumors. Because
      of their anatomical location, they often reach a large size before detection and
      are difficult to diagnose clinically because of nonspecific symptoms. After
      surgical resection, the tumors display a high rate of recurrence, thus requiring
      long-term and often indefinite follow-up. Consequently, imaging plays a central
      role in the diagnosis and management of these tumors. This review article
      examines the epidemiology, staging criteria, histologic subtypes, diagnosis,
      treatment, and general imaging principles for all retroperitoneal sarcomas, with
      detailed focus on the most common subtype, retroperitoneal liposarcomas.

PMID- 21963164
TI  - Imaging of sarcomas of pelvic bones.
AB  - Sarcomas are the most common nonhematologic primary malignancies of bones in the
      pelvis. Chondrosarcoma, osteosarcoma, and Ewing's sarcoma are the most common
      sarcomas to originate from the pelvic bones. Various imaging modalities such as
      magnetic resonance imaging and computed tomography play an important role in the
      detection, characterization, and staging of these lesions. Biopsy, usually
      performed with imaging guidance, is essential for the histologic diagnosis of
      these tumors and for planning therapeutic options. Despite considerable advances
      in treatment options, sarcomas in the pelvic bones generally are associated with
      poorer outcomes than sarcomas in the appendicular skeleton because of the larger
      size of the lesions at the time of discovery and the difficulty of obtaining a
      wide surgical resection margin. In this review, we discuss the various types of
      pelvic bone sarcomas and the role of imaging in patients with these lesions.

PMID- 21963165
TI  - Imaging of soft tissue and osseous sarcomas of the extremities.
AB  - Soft tissue and osseous sarcomas of the extremities are uncommon malignancies
      that represent very important diagnostic entities because of their aggressive
      nature. Radiologic investigations, including plain film, computed tomography,
      contrast-enhanced magnetic resonance imaging; scintigraphy, ultrasound, and
      positron emission tomography-computed tomography, play critical roles in
      providing a differential, establishing the diagnosis, demonstrating prognostic
      characteristics, and tailoring tumor treatment. The purpose of this review is to
      describe the most common soft tissue and osseous sarcomas of the extremities,
      with emphasis on their plain film and magnetic resonance imaging characteristics
      with the aim of aiding the reader to accurately describe the important imaging
      features and generate an appropriate differential diagnosis to aid the referring
      clinician with prompt appropriate management and treatment.

PMID- 21963166
TI  - Kaposi's sarcoma: imaging overview.
AB  - Kaposi's sarcoma (KS), a low-grade malignancy that is associated with human
      herpesvirus-8 (HHV-8), is a multifocal tumor that most commonly affects
      mucocutaneous sites. It might also involve lymph nodes and visceral organs, in
      particular of the respiratory and gastrointestinal tract, but it can affect every
      organ system. Four forms of the disease have been recognized: the classic, the
      endemic, the transplant-associated, and the epidemic form. The endemic form, or
      African KS, currently accounts for 10%-50% of all cancers in adults and up to 25%
      of cancers in children in certain parts of Africa. The epidemic form or acquired
      immune deficiency syndrome (AIDS)-associated KS is a frequent neoplasm in
      bisexual and homosexual men with AIDS in the United States. Even though in North
      America and Europe the incidence of KS in men with AIDS has decreased
      significantly after the introduction of highly active antiretroviral therapy
      (HAART), in some developing countries, the incidence of KS keeps growing. The
      pathophysiology, clinical manifestations, imaging findings, and more relevant
      differential diagnoses are reviewed.

PMID- 21963167
TI  - Pediatric soft tissue sarcomas.
AB  - After a brief discussion of the rarity of soft tissue sarcomas in children and of
      the limited ability of magnetic resonance imaging to provide a tissue diagnosis,
      this article discusses the incidence, presentation, treatment, prognosis, and
      imaging characteristics of the more common and unusual pediatric soft tissue
      sarcomas. It begins with extensive discussion of rhabdomyosarcoma, synovial
      sarcoma, and congenital/infantile fibrosarcoma. It then presents a more
      abbreviated discussion of uncommon tumors such as alveolar soft part sarcoma,
      epithelioid sarcoma, extraosseous Ewing's sarcoma, granulocytic sarcoma,
      hemangiopericytoma, liposarcoma, malignant fibrous histiocytoma, malignant
      peripheral nerve sheath tumor, and undifferentiated sarcoma.

PMID- 21963168
TI  - Colonocyte telomere shortening is greater with dietary red meat than white meat
      and is attenuated by resistant starch.
AB  - BACKGROUND & AIMS: Population studies indicate that greater red meat consumption
      increases colorectal cancer risk while dietary fibre is protective. Previous work
      in rats showed that diets high in protein, including red meat, increase
      colonocyte DNA strand breaks and that this effect is attenuated by resistant
      starches (RS). Telomeres are long hexamer repeats that protect against
      spontaneous DNA damage which would lead to chromosomal instability. Telomere
      shortening is associated with greater risk of colorectal cancer. The current
      study aimed to determine the effects of cooked red and white meat intake on
      colonocyte telomere length in rats and whether dietary RS modified their effects.
      METHODS: After four weeks of feeding cooked beef or chicken at 15, 25 and 35% of
      diet with or without RS, colonocyte telomere length was measured. RESULTS:
      Telomere length decreased in proportion to red meat content of the diet. A
      similar trend was observed in the white meat group. Colonocyte telomere
      shortening due to increased dietary meat was attenuated by the inclusion of RS.
      CONCLUSION: These data support previous findings of increased colonocyte DNA
      damage with greater red and white meat intake and also the protective effect of
      dietary fibre.

PMID- 21963170
TI  - Effect of N-doping on the photocatalytic activity of sol-gel TiO2.
AB  - In order to study the visible light photocatalytic activity of nitrogen doped
      titanium dioxide, the interaction between nitrogen dopant sources and titania
      precursors during sol-gel synthesis is investigated. N-TiO(2) was synthesised
      using the sol-gel method using 1,3-diaminopropane as a nitrogen source. Samples
      were annealed several temperatures and the percentage of rutile present
      determined by X-ray diffraction to be 0% (500 degrees C), 46% (600 degrees C),
      and 94% (700 degrees C). The reducing amounts of anatase at higher temperatures
      are studied using FTIR, which suggests the absence of any polymeric chains formed
      by the chelating agents, which would normally extend anatase-to-rutile
      transformation temperatures. Differential scanning calorimetry shows that
      crystalliation occurs before 500 degrees C, providing the crystalline form
      determined by XRD at 500 degrees C. Increased temperature also resulted in
      diminished visible light absorption capability, with only the 500 degrees C
      sample showing significant absorption in the visible region. XPS studies revealed
      that nitrogen remained within the TiO(2) lattice at higher temperatures.
      Consequent with the reduced visible light absorption capacity, photocatalytic
      activity also reduced with increased annealing temperature. Degradation kinetics
      of methylene blue, irradiated with a 60 W house-bulb, resulted in first order
      degradation rates constants of 0.40 * 10(-2), 0.19 * 10(-2), and 0.22 * 10(
      2)min(-1) for 500, 600, and 700 degrees C respectively. Degradation of Degussa
      P25 was minimal under the same conditions, and that of undoped TiO(2) was 0.02 *
      10(-2)min(-1). Similarly, using 4-chlorophenol under solar irradiation
      conditions, the N-doped sample at 500 degrees C substantially out-performed the
      undoped sample. These results are discussed in the context of the effect of
      increasing temperature on the nature of the band gap.

PMID- 21963171
TI  - Biodegradation of chlorobenzoic acids by ligninolytic fungi.
AB  - We investigated the abilities of several perspective ligninolytic fungal strains
      to degrade 12 mono-, di- and trichloro representatives of chlorobenzoic acids
      (CBAs) under model liquid conditions and in contaminated soil. Attention was also
      paid to toxicity changes during the degradation, estimated using two luminescent
      assay variations with Vibrio fischeri. The results show that almost all the fungi
      were able to efficiently degrade CBAs in liquid media, where Irpex lacteus,
      Pycnoporus cinnabarinus and Dichomitus squalens appeared to be the most effective
      in the main factors: degradation and toxicity removal. Analysis of the
      degradation products revealed that methoxy and hydroxy derivatives were produced
      together with reduced forms of the original acids. The findings suggest that
      probably more than one mechanism is involved in the process. Generally, the
      tested fungal strains were able to degrade CBAs in soil in the 85-99% range
      within 60 days. Analysis of ergosterol showed that active colonization is an
      important factor for degradation of CBAs by fungi. The most efficient strains in
      terms of degradation were I. lacteus, Pleurotus ostreatus, Bjerkandera adusta in
      soil, which were also able to actively colonize the soil. However, in contrast to
      P. ostreatus and I. lacteus, B. adusta was not able to significantly reduce the
      measured toxicity.

PMID- 21963169
TI  - Structural plasticity of dendritic spines.
AB  - Dendritic spines are small mushroom-like protrusions arising from neurons where
      most excitatory synapses reside. Their peculiar shape suggests that spines can
      serve as an autonomous postsynaptic compartment that isolates chemical and
      electrical signaling. How neuronal activity modifies the morphology of the spine
      and how these modifications affect synaptic transmission and plasticity are
      intriguing issues. Indeed, the induction of long-term potentiation (LTP) or
      depression (LTD) is associated with the enlargement or shrinkage of the spine,
      respectively. This structural plasticity is mainly controlled by actin filaments,
      the principal cytoskeletal component of the spine. Here we review the pioneering
      microscopic studies examining the structural plasticity of spines and propose how
      changes in actin treadmilling might regulate spine morphology.

PMID- 21963172
TI  - Co2+-exchange mechanism of birnessite and its application for the removal of Pb2+
      and As(III).
AB  - Co-containing birnessites were obtained by ion exchange at different initial
      concentrations of Co(2+). Ion exchange of Co(2+) had little effect on birnessite
      crystal structure and micromorphology, but resulted in an increase in specific
      surface areas from 19.26 to 33.35 m(2)g(-1), and a decrease in both crystallinity
      and manganese average oxidation state. It was due to that Mn(IV) in the layer
      structure was reduced to Mn(III) during the oxidation process of Co(2+) to
      Co(III). The hydroxyl groups on the surface of Co-containing birnessites
      gradually decreased with an increase of Co/Mn molar ratio owing to the occupance
      of Co(III) into vacancies and the location of large amounts of Co(2+/3+) and
      Mn(2+/3+) above/below the vacant sites. This greatly accounted for the monotonous
      reduction in Pb(2+) adsorption capacity, from 2538 mmol kg(-1) for the unmodified
      birnessite to 1500 mmol kg(-1) for the Co(2+) ion-exchanged birnessite with a
      Co/Mn molar ratio of 0.16. The amount of As(III) oxidized by birnessite was
      enhanced after ion exchange, but the apparent initial reaction rate was greatly
      decreased. The present work demonstrates that Co(2+) ion exchange has great
      influence on the adsorption and oxidation behavior of inorganic toxic metal ions
      by birnessite in water environments.

PMID- 21963173
TI  - Partitioning behavior and stabilization of hydrophobically coated HfO2, ZrO2 and
      Hfx Zr 1-x O2 nanoparticles with natural organic matter reveal differences
      dependent on crystal structure.
AB  - The interactions of engineered nanomaterials with natural organic matter (NOM)
      exert a profound influence on the mobilities of the former in the environment.
      However, the influence of specific nanomaterial structural characteristics on the
      partitioning and colloidal stabilization of engineered nanomaterials in various
      ecological compartments remains underexplored. Herein, we present a systematic
      study of the interactions of humic acid (HA, as a model for NOM) with
      monodisperse, well-characterized, ligand-passivated HfO(2), ZrO(2), and solid
      solution Hf(x)Zr(1-x)O(2) nanoparticles (NPs). We note that mixing with HA
      induces the almost complete phase transfer of hydrophobically coated monoclinic
      metal oxide (MO) NPs from hexane to water. Furthermore, HA is seen to impart
      appreciable colloidal stabilization to the NPs in the aqueous phase. In contrast,
      phase transfer and aqueous-phase colloidal stabilization has not been observed
      for tetragonal MO-NPs. A mechanistic model for the phase transfer and aqueous
      dispersal of MO-NPs is proposed on the basis of evidence from transmission
      electron microscopy, zeta-potential measurements, dynamic light scattering, Raman
      and infrared spectroscopies, elemental analysis, and systematic experiments on a
      closely related set of MO-NPs with varying composition and crystal structure. The
      data indicate the synergistic role of over-coating (micellar), ligand
      substitution (coordinative), and electrostatic processes wherein HA acts both as
      an amphiphilic molecule and a charged chelating ligand. The strong observed
      preference for the phase transfer of monoclinic instead of tetragonal NPs
      indicates the importance of the preferential binding of HA to specific
      crystallographic facets and suggests the possibility of being able to design NPs
      to minimize their mobilities in the aquatic environment.

PMID- 21963174
TI  - Geopolymers prepared from DC plasma treated air pollution control (APC) residues
      glass: properties and characterisation of the binder phase.
AB  - Air pollution control (APC) residues have been blended with glass-forming
      additives and treated using DC plasma technology to produce a high calcium
      aluminosilicate glass (APC glass). This has been used to form geopolymer-glass
      composites that exhibit high strength and density, low porosity, low water
      absorption, low leaching and high acid resistance. The composites have a
      microstructure consisting of un-reacted residual APC glass particles imbedded in
      a complex geopolymer and C-S-H gel binder phase, and behave as particle
      reinforced composites. The work demonstrates that materials prepared from DC
      plasma treated APC residues have potential to be used to form high quality pre
      cast products.

PMID- 21963175
TI  - Clinical presentation of urinary tract infection (UTI) differs with aging in
      women.
AB  - Uncomplicated UTI is among the most common health problems seen in general
      practice and typically affects immunocompetent, anatomically normal women. The
      aim of this study was to explore the difference in clinical presentation in
      acute, uncomplicated UTI in otherwise healthy community dwelling, premenopausal
      (Pre-M) and postmenopausal (Post-M) women. A UTI was defined as uropathogen of
      more than 10(3)cfu/ml in midstream urine culture. Symptoms of UTI were divided to
      three: during voiding, local symptoms, and generalized symptoms. A total of 196
      women aged a minimum of 45 years with diagnosis of UTI were studied. The patients
      were divided into two groups: Pre-M (n=102, mean age 48.14 years) and Post-M
      (n=94, mean age 69.21 years). The predominant complaints in Pre-M women were
      local symptoms. The clinical presentations showed more severity in the Post-M
      group than in Pre-M women, predominantly generalized unspecific symptoms and
      storage symptoms. Advanced age positively correlated with urgency of urination,
      painful voiding, urinary incontinence, sexual activity, low-back pain, lower
      abdominal pain and negatively correlated with frequency, painful and burning of
      urination and bladder pain. Our study showed that clinical presentation of UTI in
      Pre-M and Post-M women is different. The differences are presented not only by
      the voiding itself and by local symptoms but also by unspecified generalized
      symptoms that is especially important in elderly patients.

PMID- 21963176
TI  - Functional capacity of Brazilian patients with Parkinson's disease (PD):
      relationship between clinical characteristics and disease severity.
AB  - The present study had three objectives: (a) to characterize the functional
      capacity of patients with PD, (b) to assess the relationship between the physical
      fitness components of functional capacity with clinical characteristics and
      disease severity, and (c) to compare the physical fitness components of
      functional capacity with clinical characteristics according to disease severity.
      The study included 54 patients with idiopathic PD who were distributed into two
      groups according to PD severity: unilateral group (n=35); and bilateral group
      (n=19). All patients underwent psychiatric assessment by means of the Hoehn and
      Yahr (HY) staging of PD, the Unified Parkinson's Disease Rating Scale (UPDRS),
      the Hospital Anxiety and Depression Scale (HADS-A and HADS-D, respectively), and
      The Mini-Mental State Examination (MMSE). The physical fitness components of
      functional capacity were evaluated over a 2-day period, using recommendations by
      the American Alliance for Health, Physical Education, Recreation and Dance, and
      the Berg Balance Scale (BBS). Pearson correlation coefficients and multiple
      regressions were calculated to test the correlation between functional capacity
      and clinical characteristics, and to predict clinical scores from physical
      performance, respectively. Clinical variables and physical component data were
      compared between groups using analysis of variance to determine the effects of
      disease severity. Patients with advanced disease showed low levels of functional
      capacity. Interestingly, patients with good functional capacity in one of the
      physical fitness components also showed good capacities in the other components.
      Disease severity is a major factor affecting functional capacity and clinical
      characteristics. Medical providers should take disease severity into
      consideration when prescribing physical activity for PD patients, since the
      relationship between functional capacity and clinical characteristics is
      dependent on disease severity.

PMID- 21963177
TI  - Separation of poly-3-hydroxyvalerate-co-3-hydroxybutyrate through gradient
      polymer elution chromatography.
AB  - Polyhydroxyalkanoates are biodegradable polyesters produced by bacteria that can
      have a wide distribution in molecular weight, composition of monomers, and
      functionalities. This large distribution often leads to unpredictable physical
      properties making commercial applications challenging. To improve polymer
      homogeneity and obtain samples with a clear set of physical characteristics, poly
      3-hydroxyvalerate-co-3-hydroxybutyrate copolymers were fractionated using
      gradient polymer elution chromatography (GPEC) as opposed to extensively used
      bulk fractionation. Separation was achieved using a reversed-phase column with
      chloroform and ethanol as the solvent and non-solvent, respectively. A separation
      was also conducted on a normal-phase column to compare elution patterns between
      columns of varied polarity. The fractions were analyzed using Size Exclusion
      Chromatography (SEC) and NMR to determine the percentage of 3-hydroxyvalerate in
      the copolymer as well as its molecular weight. It was found that as the
      percentage of "good" solvent was increased in the mobile phase, the polymers
      eluted with decreasing percentage of 3-hydroxyvalerate and increasing molecular
      weight which indicates the importance of precipitation/redissolution in the
      separation. The elution pattern of the polymer remained unchanged when using both
      a normal- and reversed-phase column which also illustrates the dominance of
      precipitation/redissolution in GPEC of polyhydroxyalkanoates. As such, GPEC is
      shown to be an excellent choice to provide polyhydroxyalkanoate samples with a
      narrower distribution in composition than the original bulk copolymer sample.

PMID- 21963178
TI  - Highly sensitive oligosaccharide analysis in capillary electrophoresis using
      large-volume sample stacking with an electroosmotic flow pump.
AB  - To obtain high sensitivity in capillary electrophoresis of oligosaccharide
      without reducing the high resolution with an easy experimental procedure, large
      volume sample stacking with an electroosmotic flow pump (LVSEP) was investigated.
      As a fundamental study, effect of the conductivity of a sample solution in LVSEP
      was examined. It was revealed that LVSEP was successfully carried out even in
      using a sample solution with the ionic strength of 150 MUM and the conductivity
      ratio of 20, indicating a good applicability of LVSEP to the analysis of real
      samples containing salts. When glucose oligomer was analyzed as a model sample in
      LVSEP-capillary zone electrophoresis (CZE), all peaks were well resolved with
      decreasing only 5% of the peak-to-peak distance, which suggested 95% of the whole
      capillary could be used for the effective separation. In the analysis of
      maltoheptaose, a good calibration line with correlation coefficient of 0.9995 was
      obtained. The limit of detection was estimated as 2 pM, which was 500-fold lower
      than that in the conventional CZE. N-linked glycans released from three
      glycoproteins, bovine ribonuclease B, bovine fetuin, and human alpha(1)-acid
      glycoprotein were also analyzed by LVSEP-CZE. By the sample purification with a
      gel filtration column, further sample dilution to reduce the sample conductivity
      for LVSEP was not needed. All glycan samples were well concentrated and separated
      with up to a 770-fold sensitivity increase. The run-to-run repeatabilities of the
      migration time, peak height, and peak area were good with relative standard
      deviations of 0.1-1.3%, 1.2-1.7%, and 2.8-4.9%, respectively.

PMID- 21963179
TI  - Quantifying temperature and flow rate effects on the performance of a fixed-bed
      chromatographic reactor.
AB  - Chromatographic reactors are based on coupling chemical reactions with
      chromatographic separation in fixed-beds. Temperature and flow rate are important
      parameters for the performance of such reactors. Temperature affects mainly
      adsorption, chemical equilibria, mass transfer and reaction kinetics, whereas
      flow rate influences residence time and dispersion. In order to evaluate the
      mentioned effects, the hydrolysis reactions of methyl formate (MF) and methyl
      acetate (MA) were chosen as case studies. These reactions were performed
      experimentally in a lab-scale fixed-bed chromatographic reactor packed with a
      strong acidic ion exchange resin. The chosen reactions can be considered to
      represent a relative fast (MF) and a relative slow (MA) reaction. The processes
      which take place inside the reactor were described and simulated using an
      isothermal equilibrium dispersive model. The essential model parameters were
      determined experimentally at different temperatures and flow rates. The
      performance of the chromatographic reactor was evaluated at several discrete
      constant temperature levels by quantifying product purity, productivity and
      yield. The work provides insight regarding the influence of temperature and flow
      rate on values of the model parameters and the performance criteria.

PMID- 21963180
TI  - Kinetics of Angiotensin I alteration of conformation on different hydrophobic
      interaction chromatographic surfaces.
AB  - In the present study, Angiotensin I (Ang I) will be used as model peptide to
      assess on-column alteration of conformation phenomena. Adsorptive behavior of Ang
      I on various commercial hydrophobic interaction surfaces (Butyl, Octyl and Phenyl
      - Sepharose), under different conditions, was investigated. In order to calculate
      the cis-trans isomerization rate constants of Ang I on the stationary phase's
      surface, the first and second moments of the proline peptide elution profiles
      were determined. The activation energies for the isomerization process on Phenyl
      and Butyl Sepharose were also calculated. Results suggest that the stationary
      phase catalyzes Ang I isomerization and that catalysis is dependent on
      hydrophobic interaction ligand nature.

PMID- 21963181
TI  - Improving performance of a five-zone simulated moving bed chromatography for
      ternary separation by simultaneous use of partial-feeding and partial-closing of
      the product port in charge of collecting the intermediate-affinity solute
      molecules.
AB  - The performance of a five-zone simulated moving bed (SMB) chromatographic process
      for ternary separation has been improved to a certain extent in previous
      researches by applying either a partial-feeding (PF) or a partial-closing of the
      extract-2 port (PCE(2)) to its operation. To make a further improvement, the
      strategy of applying both PF and PCE(2) simultaneously to the five-zone SMB
      operation was proposed in this study. The results from both equilibrium-theory
      analysis and detailed simulation proved that the proposed strategy, which was
      called PF-PCE(2) in this article, had the benefit of a synergy between the
      individual merits of PF and PCE(2) in the five-zone SMB performance. As a
      consequence, the PF-PCE(2) mode could surpass the PF and the PCE(2) modes by a
      wide margin and the standard mode by a much wider margin in the aspects of
      ternary-separation performance and throughput. For the separation system
      considered, the PF-PCE(2) mode was found to achieve more than 100% improvement,
      compared to the standard mode. Furthermore, such advantage of the PF-PCE(2) over
      all the other modes was greater as the selectivity between the intermediate
      affinity and the highest-affinity components was reduced.

PMID- 21963182
TI  - Development and evaluation of new zwitterionic hydrophilic interaction liquid
      chromatography stationary phases based on 3-P,P-diphenylphosphonium
      propylsulfonate.
AB  - New zwitterionic stationary phases were synthesized by covalently bonding 3-P,P
      diphenylphosphonium-propylsulfonate to silica gel. The resulting materials
      possess both a negatively charged sulfonate group and a positively charged
      quaternary phosphonium group, which means that there is no net charge over a wide
      pH range. The retention mechanism and chromatographic behavior of polar solutes
      under HILIC conditions were studied on these zwitterionic phases. Compared to the
      commercial ZIC-HILIC column and a bare silica gel stationary phase, the newly
      synthesized zwitterionic stationary phases provided greater retention, higher
      peak efficiency and better peak symmetry in the HILIC mode. The analytes examined
      included: beta-blockers, nucleic acid bases and nucleosides, salicylic acid and
      its analogues, and water soluble vitamins. Factors, such as the type of organic
      modifiers, solvent composition, pH and the buffer concentration of the mobile
      phase, have been considered as potential variables for controlling the
      chromatographic retention of polar analytes.

PMID- 21963183
TI  - Response to letter from A.J. Gavine et al.

PMID- 21963185
TI  - A new method of surfactant administration in preterm infants.

PMID- 21963186
TI  - Avoidance of mechanical ventilation by surfactant treatment of spontaneously
      breathing preterm infants (AMV): an open-label, randomised, controlled trial.
AB  - BACKGROUND: Surfactant is usually given to mechanically ventilated preterm
      infants via an endotracheal tube to treat respiratory distress syndrome. We
      tested a new method of surfactant application to spontaneously breathing preterm
      infants to avoid mechanical ventilation. METHOD: In a parallel-group, randomised
      controlled trial, 220 preterm infants with a gestational age between 26 and 28
      weeks and a birthweight less than 1.5 kg were enrolled in 12 German neonatal
      intensive care units. Infants were independently randomised in a 1:1 ratio with
      variable block sizes, to standard treatment or intervention, and randomisation
      was stratified according to centre and multiple birth status. Masking was not
      possible. Infants were stabilised with continuous positive airway pressure and
      received rescue intubation if necessary. In the intervention group, infants
      received surfactant treatment during spontaneous breathing via a thin catheter
      inserted into the trachea by laryngoscopy if they needed a fraction of inspired
      oxygen more than 0.30. The primary endpoint was need for any mechanical
      ventilation, or being not ventilated but having a partial pressure of carbon
      dioxide more than 65 mm Hg (8.6 kPa) or a fraction of inspired oxygen more than
      0.60, or both, for more than 2 h between 25 h and 72 h of age. Analysis was by
      intention to treat. This study is registered, number ISRCTN05025922. FINDINGS:
      108 infants were assigned to the intervention group and 112 infants to the
      standard treatment group. All infants were analysed. On day 2 or 3 after birth,
      30 (28%) infants in the intervention group were mechanically ventilated versus 51
      (46%) in the standard treatment group (number needed to treat 6, 95% CI 3-20,
      absolute risk reduction 0.18, 95% CI 0.30-0.05, p=0.008). 36 (33%) infants in the
      intervention group were mechanically ventilated during their stay in the hospital
      compared with 82 (73%) in the standard treatment group (number needed to treat:
      3, 95% CI 2-4, p<0.0001). The intervention group had significantly fewer median
      days on mechanical ventilation, (0 days. IQR 0-3 vs 2 days, 0-5) and a lower need
      for oxygen therapy at 28 days (30 infants [30%] vs 49 infants [45%], p=0.032)
      compared with the standard treatment group. We recorded no differences between
      groups for mortality (seven deaths in the intervention group vs five in the
      standard treatment group) and serious adverse events (21 vs 28). INTERPRETATION:
      The application of surfactant via a thin catheter to spontaneously breathing
      preterm infants receiving continuous positive airway pressure reduces the need
      for mechanical ventilation. FUNDING: German Ministry of Research and Technology,
      University of Lubeck, and Chiesi Pharmaceuticals.

PMID- 21963187
TI  - MAPK and AP-1 proteins are increased in term pre-labour fetal membranes overlying
      the cervix: regulation of enzymes involved in the degradation of fetal membranes.
AB  - Fetal membranes overlying the cervix (i.e. supracervical site, SCS) are
      characterised by increased extracellular matrix (ECM) degradation. In non
      gestational tissues, the mitogen activated protein kinase (MAPK) and activator
      protein (AP)-1 family are involved in the regulation of the ECM degrading enzyme
      metalloproteinase (MMP)-9. The aims of this study were (i) to compare the
      expression of AP-1 proteins in fetal membranes from the SCS and a distal site
      (DS), and (ii) determine if the MAPK/AP-1 pathway is involved in the regulation
      of MMP-9. Fetal membranes overlying the cervix were identified in situ in women
      undergoing term elective Caesarean section. Immunohistochemistry (n = 6) was used
      to localise the expression of the MAPK proteins ERK (total and phosphorylated),
      JNK (total and phosphorylated) and p38 MAPK (total and phosphorylated), and the
      AP-1 proteins JunB, cJun (total and phosphorylated), JunD, cFos and FosD. There
      was no difference in JNK, p38 MAPK, FosB, cJun and JunD protein expression
      between SC and distal fetal membranes. However, when compared to DS, the
      intensity and/or extent of staining of ERK, p-ERK, p-JNK, p-p38 MAPK, cFos, JunB
      and p-cJun were greater in amnion and chorion obtained from the SCS. In order to
      elucidate a role for these proteins in ECM degradation, pharmacological
      inhibitors of MAPK protein activation were utilised in primary amnion cells. The
      ERK inhibitor U0126, JNK inhibitor SP600125 and p38 MAPK inhibitor SB202190 all
      significantly decreased IL-beta-induced MMP-9 gene expression and pro MMP-9 in
      human primary amnion cells. In summary, at term, non laboured SC fetal membranes
      are characterised by increased expression of MAPK and AP-1 proteins. MMP-9
      expression and production was significantly suppressed by inhibitors of three key
      enzymes in the signalling cascades leading to AP-1 formation, ERK 1/2, JNK and
      p38 MAPK. Thus, the MAPK/AP-1 pathway may play a role in the degradation of the
      ECM at the SCS making it more susceptible to membrane rupture.

PMID- 21963188
TI  - Health system stewardship of National Health Ministries in the WHO European
      region: concepts, functions and assessment framework.
AB  - OBJECTIVES: To propose an operational framework for assessing the completeness
      and consistency of the stewardship function of national health ministries.
      METHODS: The authors carried out a purposive and multidisciplinary review of the
      literature and derived an operational framework through iterative discussions and
      participatory methods. The results of the literature review were compared to the
      authors' observations of stewardship in action and key functions were matched
      with case examples from Europe and North America. RESULTS: The operational
      framework relates six functions of stewardship with national contexts, values and
      ultimate goals pursued by health systems: to define the vision for health and
      strategy to achieve better health; to exert influence across all sectors for
      better health; to govern the health system in a way that is consistent with
      prevailing values; to ensure that system design is aligned with health system
      goals; to better leverage available legal and regulatory instruments; and to
      compile, disseminate and apply intelligence. CONCLUSIONS: Challenges in the
      implementation of stewardship relate to: limitations to the role of health
      ministries; and to governance, operational and change implementation issues. The
      framework proposed seems flexible enough to help assess the health system
      stewardship function; however it should be further tested in practice.

PMID- 21963189
TI  - Using the diamond model to prioritize 30 causes of death by considering both the
      level of and inequality in mortality.
AB  - OBJECTIVES: The diamond model considers two dimensions of criteria, i.e., the
      magnitudes of rates and the trends in rates, in order to prioritize different
      health issues for health policy decision-making. We aimed in this study to use
      the diamond model to prioritize 30 causes of death (COD) by considering both the
      level of and inequality in mortality for the setting of policy goals in Taiwan.
      METHODS: In the level of mortality diamond, the mortality rates of 30 COD of 2006
      2008 were classified into three groups by statistical examination to construct
      the magnitude dimension of the diamond. The 30 COD were then classified into
      three groups according to statistical examination of the slope of the mortality
      trend from 1991-1993 to 2006-2008 according to linear regression to construct the
      trend dimension of the diamond. By considering the two above-described
      dimensions, each COD can be classified into one of the nine (3 by 3) grid cells
      in the diamond model, resulting in five levels of priority. The same method was
      used to construct an inequality in mortality (mortality rate ratio between the
      city/county with the highest and the lowest rate) diamond. RESULTS: In the level
      of mortality diamond, three COD were grouped in the first priority cell and seven
      in the second priority cell. However, only two COD were classified in the first
      priority cell and three in the second priority cell in the inequality in
      mortality diamond. Liver cirrhosis was the only COD in the first two priority
      cells in both diamonds. CONCLUSIONS: The diamond model is a useful tool for
      initial prioritization of health issues by considering two dimensions of criteria
      at the same time using existing data. Furthermore, by using the diamond shape to
      graphically present the prioritized results, the diamond model efficiently
      conveys prioritization information to the general public and stakeholders during
      policy debates.

PMID- 21963190
TI  - Synaptic instability in a neuronal population as an element of encoding
      information.
AB  - An unexpected and novel finding is described and discussed here concerning the
      synaptic physiology of hippocampal slices during the period of recovery after
      brain dissection. Contrary to the common notion that the amplitude of synaptic
      responses recovers in a single exponential rising fashion, we found that synaptic
      response amplitude displayed an oscillatory pattern. The period of oscillation
      was of 6h and its frequency depended on the input frequency of stimulation. Based
      on these preliminary data we can make an assumption that the recovery-associated
      oscillatory behavior of synaptic responses may be hippocampus specific. These
      data suggest the existence of a previously undescribed element that modifies the
      electrical properties underlying the modulation of synaptic responses in a
      neuronal population. The article hypothesizes a mechanism for this phenomenon.

PMID- 21963191
TI  - The investigation of the interaction between NCP-EDA and bovine serum albumin by
      spectroscopic approaches.
AB  - The fluorescence and ultraviolet spectroscopies were explored to study the
      interaction between N-confused porphyrins-edaravone diad (NCP-EDA) and bovine
      serum albumin (BSA) under simulative physiological condition at different
      temperatures. The experimental results show that the fluorescence quenching
      mechanism between NCP-EDA and BSA is a combined quenching (dynamic and static
      quenching). The binding constants, binding sites and the corresponding
      thermodynamic parameters (DeltaG, DeltaH, and DeltaS) of the interaction system
      were calculated at different temperatures. According to Forster non-radiation
      energy transfer theory, the binding distance between NCP-EDA and BSA was
      calculated to be 3.63 nm. In addition, the effect of NCP-EDA on the conformation
      of BSA was analyzed using synchronous fluorescence spectroscopy.

PMID- 21963192
TI  - FT-IR and FT-Raman spectroscopic investigation, computed vibrational frequency
      analysis and IR intensity and Raman activity peak resemblance analysis on 2
      nitroanisole using HF and DFT (B3LYP and B3PW91) calculations.
AB  - Fourier-transform Raman and infrared spectra of 2-nitroanisole are recorded (4000
      100 cm(-1)) and interpreted by comparison with respective theoretical spectra
      calculated using HF and DFT method. The geometrical parameters with C(S)
      symmetry, harmonic vibrational frequencies, infrared and Raman scattering
      intensities are determined using HF/6-311++G (d, p), B3LYP/6-311+G (d, p),
      B3LYP/6-311++G (d, p) and B3PW91/6-311++G (d, p) level of theories. A detailed
      vibrational spectral analysis has been carried out and assignments of the
      observed fundamental bands have been proposed on the basis of peak positions and
      relative intensities. The results of the calculations have been used to simulate
      IR and Raman spectra for the molecule that showed good agreement with the
      observed spectra. The SQM method, which implies multiple scaling of the DFT force
      fields has been shown superior to the uniform scaling approach. The vibrational
      frequencies and the infrared intensities of the C-H modes involved in back
      donation and conjugation are also investigated.

PMID- 21963193
TI  - Experimental (13C NMR, 1H NMR, FT-IR, single-crystal X-ray diffraction) and DFT
      studies on 3,4-bis(isoproylamino)cyclobut-3-ene-1,2-dione.
AB  - In this work, 3,4-bis(isoproylamino)cyclobut-3-ene-1,2-dione C(10)H(16)N(2)O(2)
      (I), was synthesized and characterized by (13)C NMR, (1)H NMR, FT-IR, UV-vis
      spectroscopy and single-crystal X-ray diffraction. DFT method with 6-31G(d,p)
      basis set has been used to calculate the optimized geometrical parameters, atomic
      charges, vibrational frequencies and chemical shift values. The calculated
      vibrational frequencies and chemical shift values are compared with experimental
      FT-IR and NMR spectra. The results of the calculation shows good agreement
      between experimental and calculated values of the compound I. The existence of N
      H?O type intermolecular ve C-H?O type intramolecular hydrogen bonds can be
      deduced from differences between experimental and calculated results of FT-IR and
      NMR. In addition, the molecular electrostatic potential map and frontier
      molecular orbitals and electronic absorption spectra were performed at B3LYP/6
      31G(d,p) level of theory. HOMO-LUMO electronic transition of 4.90 eV are derived
      from the contribution of the bands pi->pi* and n->pi* The spectral results
      obtained from FT-IR, NMR and X-ray of I revealed that the compound I is in
      predominantly enamine tautomeric form, which was supported by DFT calculations.

PMID- 21963194
TI  - Follicle loss after laparoscopic treatment of ovarian endometriotic cysts.
AB  - OBJECTIVE: To evaluate follicle loss and its associated factors during
      laparoscopic cystectomy for ovarian endometrioma. METHOD: Between October 2008
      and December 2009, 140 patients with ovarian cysts undergoing laparoscopic
      cystectomy at Peking Union Medical Hospital were enrolled: 74 had ovarian
      endometrioma with no preoperative hormonal therapy (group A), 40 had ovarian
      endometrioma pretreated with GnRHa (group B), and 26 had non-endometriotic cysts
      (group C). Pre-, peri- , and postoperative clinical data were collected, and cyst
      specimens were evaluated histologically. RESULTS: The number of capsules showing
      follicles and the mean number of follicles per capsule were lower in group C than
      in group A or B (P<0.05). Fewer type IIC than type IIB endometriomas showed
      follicles (P<0.05). The number of follicles per cyst was related negatively to
      disease duration but positively to pain severity. Women in group A with
      unilateral endometrioma had a lower mean dysmenorrhea score after the surgery
      (P<0.05), but no change in basal follicle-stimulating hormone (FSH). CONCLUSION:
      The type of cyst, disease duration, and severity of dysmenorrhea were associated
      with ovarian follicle loss during laparoscopic excision of endometrioma.
      Laparoscopic unilateral cystectomy for endometrioma was effective in relieving
      pain but had little effect on serum FSH, which might reflect the remaining
      ovarian reserve.

PMID- 21963195
TI  - [Cardiovascular risk evolution in patients treated for high blood pressure at the
      Armies Instruction's Hospital of Cotonou].
AB  - This study was initiated to determine the progression of the cardiovascular risk
      (CR) in a 5-years period for those who went through high blood pressure
      treatment. It is a retrospective and descriptive study over a period of 9 years.
      Were included in that category, African patients treated in that period of time
      and who at least benefited from a 5-years medical care period. The total CR was
      calculated afterwards, for the needs for the study, using the tables of
      Framingham. All the data were collected after the first evaluation then brought
      up to date at the terms of 1, 3 and 5 years and with a last consultation for the
      patients whose medical care follow-up exceeded 5 years. For the 103 patients who
      had complete data, the average age was of 49.11+/-8 and the sex ratio of 2. Among
      them 14 (13.6%) died of cardiovascular complications. Among the 89 remaining
      patients, the CR at the beginning was very high in a proportion of 10.1%, high in
      49.4%, moderated in 22.5% and weak in 18%. The general evolution is characterized
      by a stability of the proportion of the moderated CR (20 - 23%) and high CR (43 -
      50%) but a very important increase in the proportion of the very high CR (10 to
      21%) to the detriment of the weak CR (18 to 10%). The analysis of the individual
      evolution reveals an improvement of the CR among 19 patients (21.3%), its
      stability among 39 patients (43.8%) and a worsening among 31 patients (34.8%).
      These data are confirmed in a widened population of 321 patients of which the
      less complete data allow an estimate of the CR. CONCLUSION: The cardiovascular
      risk is difficult to evaluate. It is badly controlled in the long run.

PMID- 21963196
TI  - Nasogastric tube, temperature probe, and bougie stapling during bariatric
      surgery: a multicenter survey.
AB  - BACKGROUND: An adverse event in laparoscopic bariatric surgery that has not
      received much scrutiny involves tube/probe stapling or suturing during
      gastrectomy or gastroenterostomy. METHODS: A retrospective analysis was performed
      using a questionnaire sent to all bariatric surgeons (n = 43) in Israel. RESULTS:
      Eight surgeons reported on 17 cases in which intraoperative
      nasogastric/orogastric tube (n = 8), temperature probe (n = 6), or bougie
      stapling (n = 3) was identified. Laparoscopic sleeve gastrectomy was performed in
      14 patients and laparoscopic gastric bypass in 3 patients. The patient
      demographics, operative details, and postoperative results are reported.
      CONCLUSION: Tube/probe complications can occur during laparoscopic bariatric
      surgery but are seldom reported. However, they can be associated with significant
      morbidity. The treatment options are dependent on the situation. More
      importantly, prevention strategies must include constant communication with the
      anesthesiologist and removal or relocation of a tube before stapling or suturing.

PMID- 21963198
TI  - Paclitaxel-loaded expansile nanoparticles in a multimodal treatment model of
      malignant mesothelioma.
AB  - BACKGROUND: Malignant mesothelioma has a poor prognosis even when treated
      aggressively with multimodal therapy. Traditional murine tumor models can be used
      to evaluate drug efficacy and toxicity in malignant mesothelioma, but not to
      assess the effect of a multimodal approach that includes the surgical resection
      of tumor. We therefore developed a murine model of multimodal therapy in which we
      evaluated paclitaxel-loaded expansile nanoparticles (Pax-eNP) for delivering
      intracavitary chemotherapy in malignant mesothelioma. METHODS: Paclitaxel-loaded
      expansile nanoparticles (Pax-eNP) of 100 nm, designed to release drug at an
      endosomal pH below 5, were synthesized. Xenografts of human malignant
      mesothelioma were established intraperitoneally in nude mice, followed by
      cytoreductive surgery (CRS) via laparotomy, and with omentectomy and resection of
      abdominal fat pads done 14 days later. At fascial closure, 10 mg/kg paclitaxel
      was delivered as traditional paclitaxel/paclitaxel Cremophor-EL (Pax-CE) or Pax
      eNP. Morbidity and survival were assessed over a period of 90 days. RESULTS:
      Cytoreductive surgery in mice was feasible and reproducible, and incurred less
      than 5% operative mortality. By itself, CRS did not significantly prolong
      survival; however, the addition of intraoperative Pax-CE or Pax-eNP significantly
      increased survival as compared with that of mice with untreated disease. In the
      case of Pax-eNP, the increase in survival was also statistically significant as
      compared with that following resection alone. CONCLUSIONS: A murine model of CRS
      for malignant mesothelioma allows the in vivo assessment of multimodal therapy,
      including nanoparticle delivery. Combination therapy was superior to no treatment
      or CRS alone in prolonging survival. Treatment with Pax-eNP improved overall
      survival in the setting of CRS, suggesting that Pax-eNP merits further evaluation
      for intracavitary drug delivery following the surgical resection of malignant
      mesothelioma.

PMID- 21963199
TI  - The tumor microenvironment.
AB  - The concept of the tumor microenvironment, developed from Paget's "seed and soil"
      theory is made up of the cancer cells, the stromal tissue, and the extracellular
      matrix. In this mini-review, each of the components of this dynamic network will
      be examined. We will show that there are a multitude of complex interactions and
      a host of molecules involved in tumorogenesis and metastasis. We will further
      illustrate this notion with examples from the tumor microenvironment of breast
      cancer. Lastly, we conclude with thoughts about how this will influence the
      surgical field with examples of therapeutic agents already in use that target
      aspects of this microenvironment.

PMID- 21963197
TI  - Xenopus research: metamorphosed by genetics and genomics.
AB  - Research using Xenopus takes advantage of large, abundant eggs and readily
      manipulated embryos in addition to conserved cellular, developmental and genomic
      organization with mammals. Research on Xenopus has defined key principles of gene
      regulation and signal transduction, embryonic induction, morphogenesis and
      patterning as well as cell cycle regulation. Genomic and genetic advances in this
      system, including the development of Xenopus tropicalis as a genetically
      tractable complement to the widely used Xenopus laevis, capitalize on the
      classical strengths and wealth of achievements. These attributes provide the
      tools to tackle the complex biological problems of the new century, including
      cellular reprogramming, organogenesis, regeneration, gene regulatory networks and
      protein interactions controlling growth and development, all of which provide
      insights into a multitude of human diseases and their potential treatments.

PMID- 21963200
TI  - The higher susceptibility of congenital analbuminemic rats to Ca2+-induced
      mitochondrial permeability transition is associated with the increased expression
      of cyclophilin D and nitrosothiol depletion.
AB  - Congenital analbuminemia is a rare autosomal recessive disorder characterized by
      a trace level of albumin in blood plasma and mild clinical symptoms.
      Analbuminemic patients generally present associated abnormalities, among which
      dyslipidemia is a hallmark. In this study, we show that mitochondria isolated
      from different tissues (liver, heart and brain) from 3-month-old analbuminemic
      rats (NAR) present a higher susceptibility to Ca(2+)-induced mitochondrial
      permeability transition (MPT), as assessed by either Ca(2+)-induced mitochondrial
      swelling, dissipation of membrane potential or mitochondrial Ca(2+) release. The
      Ca(2+) retention capacity of the liver mitochondria isolated from 3-month-old NAR
      was about 50% that of the control. Interestingly, the assessment of this variable
      in 21-day-old NAR indicated that the mitochondrial Ca(2+) retention capacity was
      preserved at this age, as compared to age-matched controls, which indicates that
      a reduced capacity for mitochondrial Ca(2+) retention is not a constitutive
      feature. The search for putative mediators of MPT sensitization in NAR revealed a
      20% decrease in mitochondrial nitrosothiol content and a 30% increase in
      cyclophilin D expression. However, the evaluation of other variables related to
      mitochondrial redox status showed similar results between the controls and NAR,
      i.e., namely the contents of reduced mitochondrial membrane protein thiol groups
      and total glutathione, H(2)O(2) release rate, and NAD(P)H reduced state. We
      conclude that the higher expression of cyclophilin D, a major component of the
      MPT pore, and decreased nitrosothiol content in NAR mitochondria may underlie MPT
      sensitization in these animals.

PMID- 21963201
TI  - [18F-FDG PET-CT in the diagnosis of clinically unexpected tumours: clinical-
      radiological- pathological correlation].

PMID- 21963202
TI  - Postpartum screening for diabetes among Medicaid-eligible South Carolina women
      with gestational diabetes.
AB  - PURPOSE: To examine the rate of timely postpartum screening for diabetes among
      Medicaid-eligible women with gestational diabetes mellitus (GDM). METHODS: We
      examined a retrospective cohort of Medicaid women with a live birth between 2004
      and 2007. Women with singleton live births at greater than 28 weeks gestation
      were included in the cohort and their screening receipt tracked. Only the first
      qualifying pregnancy within the observation period was assessed. Birth
      certificate records were linked with hospital discharge data, outpatient prenatal
      care claims to identify women with GDM (n = 6,239). Medicaid postpartum claims
      for these women were examined to determine receipt of postpartum screening for
      diabetes within 5 to 13 weeks. Women with any indication of a dedicated plasma
      glucose test identified by CPT codes 82947, 82950, 82951, and 82952 during this
      time period were considered to meet the definition of screening. RESULTS:
      Approximately 3.4% of women identified as having GDM were screened for diabetes
      postpartum. Adjusted analysis found women not attending the postpartum visit
      (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.37-0.91) and women
      receiving inadequate prenatal care (OR, 0.57; 95% CI, 0.34-0.95) were less likely
      to receive postpartum screening for diabetes. Conversely, women 20 to 34 years of
      age (OR, 1.79; 95% CI, 1.21-2.66) and women who were obese (OR, 2.28; 95% CI,
      1.56-3.32) were more likely to be screened. CONCLUSIONS: Medicaid is a primary
      source of insurance for many women; however, for most coverage ends at 60 days
      postpartum, leaving a narrow window of opportunity for postpartum screening.
      Extended periods of coverage may be beneficial in ensuring the opportunity to
      receive adequate postpartum care, including screening for diabetes.

PMID- 21963203
TI  - Patterning of Gd2(WO4)3:Ln3+ (Ln=Eu, Tb) luminescent films by microcontact
      printing route.
AB  - Gd(2)(WO(4))(3) doped with Eu(3+) or Tb(3+) thin phosphor films with dot patterns
      have been prepared by a combinational method of sol-gel process and microcontact
      printing. This process utilizes a PDMS elastomeric mold as the stamp to create
      heterogeneous pattern on quartz substrates firstly and then combined with a
      Pechini-type sol-gel process to selectively deposit the luminescent phosphors on
      hydrophilic regions, in which a Gd(2)(WO(4))(3):Ln(3+) (Ln=Eu, Tb) precursor
      solutions were employed as ink. X-ray diffraction (XRD), scanning electron
      microscopy (SEM), photoluminescence (PL) spectra, as well as low voltage
      cathodoluminescence (CL) spectra were carried out to characterize the obtained
      samples. Under ultraviolet excitation and low-voltage electron beams excitation,
      the Gd(2)(WO(4))(3):Eu(3+) samples exhibit a strong red emission arising from
      Eu(3+)(5)D(0,1,2)-(7)F(1,2) transitions, while the Gd(2)(WO(4))(3):Tb(3+) samples
      show the green emission coming from the characteristic emission of Tb(3+)
      corresponding to (5)D(4)-(7)F(6,5,4,3) transitions. The results show that the
      patterning of rare earth-doped phosphors through combining microcontact printing
      with a Pechini-type sol-gel route has potential for field emission displays
      (FEDs) applications.

PMID- 21963204
TI  - Mechanism of interaction of hydrocalumites (Ca/Al-LDH) with methyl orange and
      acidic scarlet GR.
AB  - The development of new materials for water purification is of universal
      importance. Among these types of materials are layered double hydroxides (LDHs).
      Non-ionic materials pose a significant problem as pollutants. The interaction of
      methyl orange (MO) and acidic scarlet GR (GR) adsorption on hydrocalumite (Ca/Al
      LDH-Cl) was studied by X-ray diffraction (XRD), infrared spectroscopy (MIR),
      scanning electron microscope (SEM), and near-infrared spectroscopy (NIR). The XRD
      results revealed that the basal spacing of Ca/Al-LDH-MO was expanded to 2.45 nm,
      and the MO molecules were intercalated with a interpenetrating bilayer model in
      the gallery of LDH, with 49 degrees  tilting angle. Yet, Ca/Al-LDH-GR was kept
      the same d-value as Ca/Al-LDH-Cl. The NIR spectrum for Ca/Al-LDH-MO showed a
      prominent band around 5994 cm(-1), assigned to the combination result of the NH
      stretching vibrations, which was considered as a mark to assess MO(-) ion
      intercalation into Ca/Al-LDH-Cl interlayers. From SEM images, the particle
      morphology of Ca/Al-LDH-MO mainly changed to irregular platelets, with a "honey
      comb" like structure. Yet, the Ca/Al-LDH-GR maintained regular hexagon platelets,
      which was similar to that of Ca/Al-LDH-Cl. All results indicated that MO(-) ion
      was intercalated into Ca/Al-LDH-Cl interlayers, and acidic scarlet GR was only
      adsorbed upon Ca/Al-LDH-Cl surfaces.

PMID- 21963205
TI  - The interaction between G-quadruplex-forming oligonucleotide and cationic
      surfactant monolayer at the air/water interface.
AB  - We report on the interactions between a 21-mer quadruplex-forming oligonucleotide
      bearing human telomere sequence of dG(3)(T(2)AG(3))(3) (G4 DNA) and a positively
      charged dioctadecyldimethylammonium bromide (DODAB) monolayer at the air-aqueous
      interface, studied by surface film balance measurements. In the presence of G4
      DNA, the pi-A isotherm of the cationic Langmuir film shifted to lower molecular
      areas when compared with the reference isotherm recorded on the subphase
      containing only 50 mM triethylamine-acetate (TEAA) buffer. The presence of
      quadruplex-stabilizing metal cations (K(+) or Na(+)) further affected profiles of
      pi-A isotherms. Further insight into processes related to the G4 DNA-monolayer
      interactions was provided by recording time profiles of the surface pressure of
      monolayer at a constant mean molecular area. In these experiments G4 DNA and/or
      metal ions were sequentially injected under the monolayer surface. Results
      indicated that multistranded assemblies of G4 DNA were formed at the monolayer
      interface even in the absence of metal ions, which suggested that the charged
      cationic surface of Langmuir monolayer induced aggregation of guanine-rich DNA
      strands. The presence of sodium and potassium ions inhibited formation of multi
      stranded assemblies through the competitive G-quadruplex formation but to
      different extent that might be related to the differences in stability and
      topology of both quadruplexes.

PMID- 21963206
TI  - Interfacial and self-assembly properties of bolaamphiphilic compounds derived
      from a multifunctional oil.
AB  - The self-assembly characteristics in aqueous solutions of cationic
      bolaamphiphiles with systematic changes in their chemical structure is described
      with respect to their interfacial properties within water and at the air/water
      interface. Six cationic bolaamphiphiles were synthesized from multifunctional
      vernonia oil with the following variations: (a) two different alkyl chain lengths
      connecting the head groups, (b) polar ester or hydrogen bonding amide groups
      within the hydrophobic domain, and (c) an acetylcholine cationic head group with
      different conjugation sites to the alkyl chain. Surface tension measurements were
      used for determining critical aggregation concentration (CAC) values and
      air/water interfacial parameters such as 'effectiveness', surface excess
      concentration and area occupied by one molecule in the air/water interface.
      Fluorescent studies with pyrene were used to characterize CAC properties within
      the aqueous volume and transmission electron microscopy (TEM) for determining the
      aggregate structure's size, homogeneity and morphology. A bolaamphiphile
      molecular structure vs. interfacial property relationship was derived from this
      data which could be used to determine the molecular structure properties needed
      to generate interfacial forces to form either spherical vesicles or fibrous
      networks. The effects of the aliphatic chain length, head group orientation and
      functional groups within the hydrophobic domain on CAC, surface tension
      properties and self-aggregate morphology are described. Most bolaamphiphiles
      studied had CAC values in the 10-190 MUM range, while two out of the six were
      found to assemble into MLM spherical vesicles with diameters ranging up to 120 nm
      suitable for drug delivery applications. Others formed a gelatinous network of
      fibers or multi-lamellar vesicles.

PMID- 21963207
TI  - Interactions of salicylic acid derivatives with calcite crystals.
AB  - Investigation of basic interactions between the active pharmaceutical compounds
      and calcium carbonates is of great importance because of the possibility to use
      the carbonates as a mineral carrier in drug delivery systems. In this study the
      mode and extent of interactions of salicylic acid and its amino acid derivates,
      chosen as pharmaceutically relevant model compounds, with calcite crystals are
      described. Therefore, the crystal growth kinetics of well defined rhombohedral
      calcite seed crystals in the systems containing salicylic acid (SA), 5-amino
      salicylic acid (5-ASA), N-salicyloil-l-aspartic acid (N-Sal-Asp) or N-salicyloil
      l-glutamic acid (N-Sal-Glu), were investigated. The precipitation systems were of
      relatively low initial supersaturation and of apparently neutral pH. The data on
      the crystal growth rate reductions in the presence of the applied salicylate
      molecules were analyzed by means of Cabrera & Vermileya's, and Kubota & Mullin's
      models of interactions of the dissolved additives and crystal surfaces. The
      crystal growth kinetic experiments were additionally supported with the
      appropriate electrokinetic, spectroscopic and adsorption measurements. The
      Langmuir adsorption constants were determined and they were found to be in a good
      correlation with values obtained from crystal growth kinetic analyses. The
      results indicated that salicylate molecules preferentially adsorb along the steps
      on the growing calcite surfaces. The values of average spacing between the
      adjacent salicylate adsorption active sites and the average distance between the
      neighboring adsorbed salicylate molecules were also estimated.

PMID- 21963208
TI  - Rate vs. rhythm control in patients with atrial fibrillation--an updated meta
      analysis of 10 randomized controlled trials.

PMID- 21963209
TI  - Socioeconomic status on exercise capacity in adults with congenital heart disease
      -"the direction forward".

PMID- 21963210
TI  - Gadolinium-enhanced cardiovascular magnetic resonance for the detection and
      characterization of Loeffler endocarditis in patients with hypereosinophilic
      syndrome.

PMID- 21963211
TI  - Obesity-related autonomic nervous system disorders are best associated with body
      fat mass index, a new indicator.

PMID- 21963212
TI  - Percutaneous transluminal intervention and antiplatelet therapy following
      endovascular graft exclusion for Stanford B thoracic aortic dissection.
AB  - OBJECTIVE: To evaluate the safety and feasibility of percutaneous coronary
      intervention and antiplatelet therapy in patients who have undergone endovascular
      graft exclusion. METHODS: From January 2005 to July 2007, percutaneous
      transluminal intervention (PCI) was performed in 13 patients who had undergone
      endovascular graft exclusion for the treatment of either acute or chronic
      Stanford B aortic dissection. Anticoagulant and antiplatelet treatments were
      administered according to the standard protocol. Patients were followed up for a
      mean period of 11 months. Clinical characteristics, false lumen thrombosis and
      angiographic data were collected. RESULTS: PCI was technically successful in all
      13 patients and no severe complications, including death, paraplegia or renal
      failure occurred during hospitalization. Complete false lumen thrombosis was
      observed in all patients within 6 months. There were no major complications such
      as death, dissection rupture, or aneurysm development during the follow-up
      period. CONCLUSION: Our data suggested that PCI and standard antiplatelet therapy
      are feasible and safe in patients who have undergone endovascular stent graft
      exclusion for Stanford B aortic dissection.

PMID- 21963213
TI  - Emotional distress, positive affect, and mortality in patients with an
      implantable cardioverter defibrillator.
AB  - BACKGROUND: Little is known about the relationship between emotional distress and
      mortality in patients with an implantable cardioverter defibrillator (ICD). Our
      aim was to examine the predictive value of general negative and positive affect,
      and depressive symptoms (including its components somatic symptoms and cognitive
      affective symptoms) for mortality. METHODS: ICD patients (N=591, 81% male, mean
      age=62.7 +/- 10.1 years) completed the Global Mood Scale to measure the
      independent dimensions negative and positive mood, and the Beck Depression
      Inventory to measure depressive symptoms. Covariates consisted of demographic and
      clinical variables. RESULTS: During the median follow-up of 3.2 years, 96 (16.2%)
      patients died. After controlling for covariates, negative affect was
      significantly related to all-cause mortality (HR=1.034, p=0.002), whereas
      positive affect was not (HR=1.007, p=0.61). Depressive symptoms were also
      independently associated with an increased mortality risk (HR=1.031, p=0.030) and
      somatic symptoms of depression in particular (HR=1.130, p=0.003), but cognitive
      affective symptoms were not associated with mortality (HR=0.968, p=0.29). When
      entering both significant psychological predictors in a covariate-adjusted model,
      negative mood remained significant (HR=1.039, p=0.009), but somatic symptoms of
      depression did not (HR=0.988, p=0.78). Similar results were found for cardiac
      related death. Of covariates, increased age, CRT, appropriate shocks were
      positively related to death. CONCLUSIONS: Negative affect in general was related
      to mortality, but reduced positive affect was not. Depression, particularly its
      somatic symptoms, was also related to mortality, while cognitive-affective
      symptoms were not. Future research may further focus on the differential
      predictive value of emotional distress factors, as well as on mechanisms that
      relate emotional distress factors to mortality.

PMID- 21963214
TI  - Potential mechanisms of the acute coronary syndrome presentation in patients with
      the coronary slow flow phenomenon - insight from a plasma proteomic approach.
AB  - AIMS: The coronary slow flow phenomenon [CSFP] is a coronary microvascular
      disorder, characterized by delayed distal vessel opacification despite the
      absence of obstructive coronary artery disease. Patients frequently present with
      an acute coronary syndrome [ACS] although the pathophysiological mechanisms
      responsible are unknown. The aim of this study was to identify potential
      mechanisms for the ACS presentation associated with the CSFP using a plasma
      proteomic profiling approach. METHODS AND RESULTS: Plasma samples from nine CSFP
      subjects [56 +/- 11years] were assayed for high sensitivity C-reactive protein
      [hsCRP], troponin T [TnT], creatine kinase [CK], and proteomic analyses (n=6),
      during an ACS presentation and one month later [chronic phase]. Proteomic
      analysis involved chromatographic depletion of abundant plasma proteins followed
      by two-dimensional differential gel electrophoresis [2-D DIGE]. Protein spots
      demonstrating +/-1.5-fold change relative to the control were identified by mass
      spectrometry and two differentially expressed proteins were selected for
      validation via Western blotting. During the ACS presentation, hsCRP was elevated
      [ACS=14.9 +/- 3.9 mg/L vs chronic=4.23 +/- 1.37 mg/L, p=0.05] but TnT and CK
      levels were unchanged. Proteomic analysis identified six proteins that were
      significantly different in abundance between the acute and chronic samples.
      During the ACS presentation there was a 1.6 +/- 0.13 fold increase in the anti
      oxidant enzyme paraoxonase-1 and an increase in inflammatory proteins alpha-1
      antichymotrypsin [1.65 +/- 0.13 fold] and alpha-1-antitrypsin [2.5 +/- 0.34
      fold]. The latter was confirmed by Western blotting [1.33 +/- 0.17 OD
      acute/chronic ratio, p=0.05]. CONCLUSION: The findings from this novel detailed
      approach, implicate an inflammatory/oxidative stress process in the pathogenesis
      of the ACS presentation associated with the CSFP. Future studies should further
      elucidate these mechanisms.

PMID- 21963215
TI  - Modulation of CYP1A and genotoxic effects in European seabass (Dicentrarchus
      labrax) exposed to weathered oil: a mesocosm study.
AB  - The aim of this study was to assess medium-term toxicity of weathered oil on
      European seabass. A mesocosm system reproducing an oil spill at sea was applied.
      Fish were collected after 48 h, 7, 30 and 60 days. Cyp1a gene transcription, EROD
      and UDPGT activities, bile PAHs metabolites and micronuclei frequency were
      investigated. A progressive disappearance of low molecular weight n-alkanes and
      PAHs in the water of the mesocosm occurred during the experimentation. Fishes
      exposed to oil displayed a significant increase of cyp1a expression and EROD
      activity during the entire experiment as well as higher concentrations of PAHs
      metabolites in bile. Micronulei frequency resulted significantly higher during
      all experiment in oil exposed sea bass compared to controls. The results
      highlight the environmental risk associated with the release of oil products at
      sea and confirm the adopted parameters as useful tools for studying the impact of
      accidental oil spills on fish.

PMID- 21963216
TI  - Neighborhood disorder and anxiety symptoms: new evidence from a quasi
      experimental study.
AB  - This paper examines the relationship between neighborhood disorder and anxiety
      symptoms. It draws on data from the Monitoring Mt. Laurel Study, a new survey
      based study that enables us to compare residents living in an affordable housing
      project in a middle-class New Jersey suburb to a comparable group of non
      residents. Using these new data, we test the hypothesis that living in an
      affordable housing project in a middle class suburb reduces a poor person's
      exposure to disorder and violence compared to what they would have experienced in
      the absence of access to such housing, and that this lesser exposure to disorder
      and violence yields improvements in anxiety that can be attributed to residents'
      reduced stress burden. We find that residents of the project are less likely to
      be exposed to disorder and violence and have lower stress levels and slightly
      fewer anxiety symptoms. Differences in exposure to disorder explain differences
      in stress burden, and, hence, anxiety symptoms between the two groups.

PMID- 21963217
TI  - Nitric oxide generation affects pro- and anti-angiogenic growth factor expression
      in primary human trophoblast.
AB  - OBJECTIVES: Preeclampsia is associated with reduced trophoblast placenta growth
      factor (PGF) expression, elevated soluble fms-like tyrosine kinase-1 (sFlt-1) and
      decreased bioactivity of nitric oxide (NO). Elevated sFlt-1 reduces bio
      availability of PGF and vascular endothelial growth factor (VEGF) leading to
      maternal endothelial dysfunction. Although NO can regulate gene expression, its
      ability to regulate trophoblast expression of angiogenic growth factors is not
      known. STUDY DESIGN: Human primary term trophoblast and JEG-3 choriocarcinoma
      cells were cultured under 21%O(2) or 1%O(2) conditions in the presence or absence
      of NO donor (SNP) or inhibitor (L-NAME). Effects on PGF, VEGF and Flt-1 isoform
      mRNA expression were determined by quantitative real-time PCR. Changes in
      expression of soluble protein isoforms of FLT-1 was monitored by ELISA. RESULTS:
      Hypoxia decreased PGF mRNA but increased VEGF, sFlt-1 and Flt-1 mRNA expression
      in trophoblast. Generation of NO in trophoblast under 1%O(2) culture conditions
      significantly reversed sFlt-1 mRNA and protein expression, independent of mFlt-1.
      Conversely NO generation in hypoxic trophoblast increased VEGF and PGF mRNA
      expression. CONCLUSIONS: NO production in primary human trophoblast cultures had
      divergent effects on pro-angiogenic (PGF, VEGF) versus anti-angiogenic (sFlt-1)
      mRNA expression, resulting in an enhanced pro-angiogenic gene expression
      environment in vitro.

PMID- 21963218
TI  - Elevated admission blood pressure and acute ischemic lesions in spontaneous
      intracerebral hemorrhage.
AB  - Concomitant acute ischemic lesions are detected in a subset of patients with
      intracerebral hemorrhage (ICH). In this study, our aim was to analyze the pattern
      of acute ischemic lesions detected by diffusion-weighted imaging (DWI) in
      patients with ICH, and to use this information, in combination with clinical
      characteristics of patients, to understand the underlying mechanisms of these
      lesions. We retrospectively analyzed patients with a diagnosis of ICH who
      underwent DWI within 14 days of symptom onset. We compared demographic, clinical,
      and imaging characteristics in patients with and without acute ischemic lesions.
      We also assessed the number, location, and topographic distribution of DWI bright
      lesions. Acute ischemic lesions were detected in 15 of 86 patients (17.4%); the
      lesions had a small, dot-like appearance in 13 patients (87%) and were located in
      an arterial territory separate from the incident ICH in 12 patients (80%).
      Patients with acute ischemic lesions had higher admission systolic, diastolic,
      and mean arterial blood pressure levels; greater periventricular leukoaraiosis
      burden; more microbleeds, and lower admission Glasgow Coma Scale score. In
      multivariate analyses, admission mean arterial blood pressure (P < .01) and
      Glasgow Coma Scale score (P =.03) remained as the only significant variables
      associated with DWI lesion positivity. Our findings highlight the role of
      elevated admission blood pressure in the development of concomitant acute
      ischemic lesions in patients with ICH. The pattern of DWI bright lesions,
      together with a trend toward an increased burden of leukoaraiosis and microbleeds
      in patients with acute ischemic lesions, suggest an underlying dysfunctional
      cerebral microvasculature in the etiology of these lesions.

PMID- 21963219
TI  - Determinants of emergency medical services use in a Brazilian population with
      acute ischemic stroke.
AB  - Emergency medical services (EMS) plays a key role in the recognition and
      treatment of stroke. This study evaluates the determinants of EMS use in a
      Brazilian population with acute ischemic stroke. We performed a post hoc analysis
      of prospectively collected data of consecutive patients admitted to a Brazilian
      tertiary hospital with acute ischemic stroke. Groups were compared according to
      their mode of arrival to the hospital: those brought by EMS and those arriving at
      the hospital by their own means. Among 165 patients evaluated between January and
      December 2009, 17.6% arrived by EMS and 82.4% arrived by their own means. After
      multivariate adjustment, individuals with higher National Institutes of Health
      Stroke Scale score at presentation (odds ratio [OR], 1.15; 95% confidence
      interval [CI], 1.06-1.23 for each point on the National Institutes of Health
      Stroke Scale score) were more likely to use EMS, as were those with atrial
      fibrillation (OR, 5.8; 95% CI, 1.41-24.07) and with lower blood pressure at
      hospital admission (OR, 0.72; 95% CI, 0.56-0.93 for each mm Hg). Patients brought
      by EMS had trends toward a lower door-to-neuroimaging time and a higher frequency
      of thrombolysis therapy (13% in EMS users vs 5% in patients arriving by their own
      means; P = .10). Our data demonstrate that in a Brazilian population with acute
      ischemic stroke, the patients with more severe stroke, those with atrial
      fibrillation, and those with lower blood pressure at hospital presentation were
      more likely to use EMS. EMS use was associated with trends toward a lower door-to
      neuroimaging time and a higher frequency of thrombolysis therapy.

PMID- 21963221
TI  - Expression of tumor necrosis factor-alpha induced protein 8 like-2 contributes to
      the immunosuppressive property of CD4(+)CD25(+) regulatory T cells in mice.
AB  - Tumor necrosis factor-alpha induced protein 8 like-2 (TNFAIP8L2, TIPE2), a lately
      discovered negative regulator of innate immunity and cellular immunity, shares
      considerable sequence homology with members of the tumor necrosis factor-alpha
      induced protein 8 (TNFAIP8) family. It is preferentially expressed in lymphoid
      derived and marrow-derived cells. However, it is unclear whether TIPE2 is
      expressed in the regulatory T cells (Tregs) to contribute to its negative
      regulatory property in immune response. The present study was designed to examine
      whether naturally occurring CD4(+)CD25(+) Tregs isolated from murine spleens
      expressed TIPE2 by the use of Western blot and reverse transcription-polymerase
      chain reaction (RT-PCR). Based on the expression of cell surface molecules,
      including cytotoxic T-lymphocyte-associated antigen (CTLA)-4 and forkhead/winged
      helix transcription factor p3 (Foxp3) on CD4(+)CD25(+) Tregs, and cytokines
      including interleukin (IL)-10 as well as transforming growth factor (TGF)-beta
      were analyzed to investigate the functional role of TIPE2 in controlling
      suppressive activity of CD4(+)CD25(+) Tregs. Meanwhile, IL-2, the ratio of
      interferon (IFN)-gamma/IL-4 in CD4(+)CD25(+)Treg/CD4(+)CD25(-) T cell coculture
      supernatant and nuclear factor of activated T cells (NF-AT) activation in T
      lymphocytes were determined to examine the effects of TIPE2 on the T-cell
      proliferation and differentiation induced by CD4(+)CD25(+) Tregs. It was found
      that TIPE2 was a cytoplasmic protein expressed in CD4(+)CD25(+) Tregs, and cell
      surface molecules as well as cytokines (IL-10, TGF-beta) expressions were
      significantly down-regulated when TIPE2 gene silenced by siRNA. On the other
      hand, CD4(+)CD25(+) Tregs treated with TIPE2 knock-down promoted T-cell
      proliferation as well as differentiation, and markedly upregulated IL-2
      expression and intranuclear NF-AT activation. The results suggested that TIPE2
      appeared to be a critical immunoregulatory molecule involved in immunosuppressive
      function of CD4(+)CD25(+) Tregs.

PMID- 21963220
TI  - The transcription factor Bright plays a role in marginal zone B lymphocyte
      development and autoantibody production.
AB  - Previous data suggested that constitutive expression of the transcription factor
      Bright (B cell regulator of immunoglobulin heavy chain transcription), normally
      tightly regulated during B cell differentiation, was associated with autoantibody
      production. Here we show that constitutive Bright expression results in skewing
      of mature B lineage subpopulations toward marginal zone cells at the expense of
      the follicular subpopulation. C57Bl/6 transgenic mice constitutively expressing
      Bright in B lineage cells generated autoantibodies that were not the result of
      global increases in immunoglobulin or of breaches in key tolerance checkpoints
      typically defective in other autoimmune mouse models. Rather, autoimmunity
      correlated with increased numbers of marginal zone B cells and alterations in the
      phenotype and gene expression profiles of lymphocytes within the follicular B
      cell compartment. These data suggest a novel role for Bright in the normal
      development of mature B cell subsets and in autoantibody production.

PMID- 21963222
TI  - [Contact sensitization to allergens in the Spanish standard series at Hospital
      Costa del Sol in Marbella, Spain: a retrospective study (2005-2010)].
AB  - BACKGROUND: The prevalence of contact allergy to different compounds can vary
      according to the population studied, the technique used, and the materials
      employed in patch tests. The Spanish Contact Dermatitis and Skin Allergy Research
      Group (GEIDAC) has proposed a panel of 29 allergens for use in patients with
      suspected allergic contact dermatitis. OBJECTIVE: To determine the prevalence of
      contact sensitization in a group of Spanish patients and to analyze potential
      associations with sociodemographic and clinical variables (sex, age, site of
      lesions, occupation, and diagnosis of atopic dermatitis). MATERIAL AND METHODS: A
      retrospective study of patients with suspected contact dermatitis was undertaken
      at Hospital Costa del Sol in Marbella, Spain, for the period between January 1,
      2005 and December 31, 2010; 839 patients were included in the analysis. Patch
      tests were carried out with 34 allergens, including the 29 compounds that
      comprise the Spanish standard panel proposed by the GEIDAC. RESULTS:
      Sensitization to at least 1 allergen in the panel was observed in 48% of
      patients. Women had a higher frequency of sensitization than men (56.9% vs
      33.1%). The hands were the most commonly affected site (36.1%). The most
      frequently involved allergens were nickel sulfate (25.9%), potassium dichromate
      (7.6%), thiomersal (5.1%), cobalt chloride (4.5%), and fragrance mix I (3.8%). In
      contrast, preservatives such as paraben mix (0.1%), imidazolidinyl urea (0.1%),
      diazolidinyl urea (0.2%), and quinoline mix (0.2%) had low rates of
      sensitization. Sensitization to sesquiterpene lactones and methyldibromo
      glutaronitrile (euxyl K 400) were not observed. CONCLUSIONS: Our results are
      similar to those previously reported for Spanish patients. The low level of
      sensitization to certain allergens such as most preservatives and sesquiterpene
      lactones may suggest that their use in standard patch test series should be
      reconsidered.

PMID- 21963223
TI  - A possible role of cIAP2 in Helicobacter pylori-associated gastric cancer.
AB  - Cellular inhibitor of apoptosis protein 2 (cIAP2) is a member of the IAP family
      and is over-expressed in most cancer tissues. In this study, we investigated the
      role cIAP2 in Helicobacter pylori (HP) related gastric carcinogenesis. We
      measured the expression of cIAP2 at mRNA and protein levels in a panel of gastric
      cancer cell lines and human gastric cancer tissues by semi-quantitative reverse
      transcriptase PCR (RT-PCR), quantitative real time PCR (qPCR), immunoblotting,
      and immunohistochemistry. The effects of cIAP2 down-regulation on gastric cell
      proliferation and apoptosis were detected by standard WST-1 assay and flow
      cytometry, respectively. Infection of gastric mucosa by HP enhances the
      expression of cIAP2 in mouse gastric tissues. Over 70% of human gastric cancer
      tissues express higher amount of cIAP2. Well-differentiated gastric cancer cells
      express more cIAP2 than moderately- and poorly-differentiated gastric cancer
      cells. Knocking down of cIAP2 in SGC-7901 cells results in a 30% decrease in cell
      proliferation, a 20% increase in apoptosis and delayed migration. Thus, cIAP2 may
      play an important role in HP-induced gastric carcinogenesis, and it may serve as
      a potential target for gastric cancer therapy.

PMID- 21963224
TI  - An RNA aptamer that specifically binds pancreatic adenocarcinoma up-regulated
      factor inhibits migration and growth of pancreatic cancer cells.
AB  - Previously, we reported that a novel secretory protein, pancreatic adenocarcinoma
      up-regulated factor (PAUF), which is highly expressed in pancreatic cancer and
      mediates the growth and metastasis of pancreatic cancer cells. In this study, we
      generated and characterized a 2'-fluoropyrimidine modified RNA aptamer (P12FR2)
      directed against human PAUF. P12FR2 binds specifically to human PAUF with an
      estimated apparent K(D) of 77nM. P12FR2 aptamer inhibits PAUF-induced migration
      of PANC-1, human pancreatic cancer cells, in a wound healing assay. Moreover,
      intraperitoneal injection of P12FR2 decreased tumor growth by about 60% in an in
      vivo xenograft model with CFPAC-1 pancreatic cancer cells, without causing a loss
      of weight in the treated mice. Taken together, we propose here that PAUF-specific
      RNA aptamer, P12FR2, has the potential to be effective in the therapy of human
      pancreatic cancer.

PMID- 21963225
TI  - Lunasin potentiates the effect of oxaliplatin preventing outgrowth of colon
      cancer metastasis, binds to alpha5beta1 integrin and suppresses FAK/ERK/NF-kappaB
      signaling.
AB  - The effect of lunasin on colon cancer metastasis was studied using three human
      colon cancer cell lines in vitro and a liver metastasis model of colon cancer in
      vivo. Lunasin bound with alpha5beta1 integrin and internalized into the nucleus
      of KM12L4 human colon cancer cells. Lunasin (10 MUM) inhibited the activation of
      focal adhesion kinase (FAK) by 28%, 39% and 60% in RKO, HCT-116 and KM12L4 human
      colon cancer cells, respectively. Lunasin caused an increase in the expression of
      the inhibitor of kappa B alpha (IkappaB-alpha), a decrease in nuclear p50 NF
      kappaB and a reduction in the migration of cancer cells. Lunasin (4 mg/kg bw)
      inhibited metastasis and potentiated the effect of oxaliplatin by reducing the
      expression of proliferating cell nuclear antigen. Liver metastatic nodules were
      reduced from 28 (PBS) to 14 (lunasin, P = 0.047) while combination of lunasin and
      oxaliplatin to 5 (P = 0.004). The tumor burden was reduced from 0.13 (PBS) to
      0.10 (lunasin, P = 0.039) to 0.04 (lunasin + oxaliplatin, P < 0.0001). Moreover,
      lunasin potentiated the effect of oxaliplatin in modifying expression of proteins
      involved in apoptosis and metastasis including Bax, Bcl-2, IKK-alpha and p-p65.
      Lunasin inhibited metastasis of human colon cancer cells by direct binding with
      alpha5beta1 integrin suppressing FAK/ERK/NF-kappaB signaling, and potentiated the
      effect of oxaliplatin in preventing the outgrowth of metastasis.

PMID- 21963227
TI  - The phenotype of polycystic ovary syndrome ameliorates with aging.
AB  - OBJECTIVE: To assess the effects of aging on the features of polycystic ovary
      syndrome (PCOS). DESIGN: Retrospective longitudinal follow-up study. SETTING:
      Tertiary care center. PATIENT(S): Patients with PCOS, diagnosed according to the
      2003 Rotterdam criteria, who visited the outpatient clinic on consecutive
      occasions with a minimum interval of 6 months. INTERVENTION(S): Comparisons were
      made between the first visit and the consecutive visit grouped by intervals. MAIN
      OUTCOME MEASURE(S): Changes in clinical and endocrine characteristics. RESULT(S):
      A total of 254 women visited the outpatient clinic on 2 occasions each.
      Consecutive visits were grouped into 0.5 to 3.9 years (n = 172; mean follow-up,
      2.6 years) and 4.0 to 7.0 years (n = 82; mean follow-up, 5.5 years). At their
      second visit, significantly more women had regained a regular cycle. The total
      antral follicle count was similar. Serum levels of testosterone, androstenedione,
      and dehydroepiandrosterone sulfate had decreased significantly. Plasma glucose
      levels had increased, whereas serum insulin levels and homeostasis model
      assessment score had significantly decreased. CONCLUSION(S): The PCOS phenotype
      changed with aging, suggesting an amelioration of the phenotype and ovarian
      dysfunction as indicated by the increase in number of regular menstrual cycles,
      decrease in serum androgen levels, and decrease in insulin resistance.

PMID- 21963228
TI  - Evaluation of the effects of gonadotropin-releasing hormone antagonist (GnRH-ant)
      and agonist (GnRH-a) in the prevention of postoperative adhesion formation in a
      rat model with immunohistochemical analysis.
AB  - OBJECTIVE: To investigate the effects of GnRH antagonist (GnRH-ant) and agonist
      (GnRH-a) in the prevention of postoperative pelvic adhesions by a visual scoring
      system and immunohistochemical methods in a rat uterine horn model. DESIGN:
      Controlled experimental animal study. SETTING: Animal laboratory at an academic
      research environment. ANIMAL(S): Twenty-one Wistar albino rats. INTERVENTION(S):
      Rats were randomized into three groups. One week before the operation the rats
      received either GnRH-ant or GnRH-a or saline solution; they then underwent
      surgical laparotomy, and both uterine horns were traumatized by a scalpel. Three
      weeks later, all rats were sacrificed and extension and severity of the adhesions
      in each group were scored by a visual scoring system. Adhesion tissues were
      evaluated immunohistochemically for vitronectin and u-PAR. MAIN OUTCOME
      MEASURE(S): Scores of extend and severity of adhesions and staining of
      vitronectin and u-PAR. RESULT(S): The extent of adhesion scores were 1.85 +/-
      0.86, 0.78 +/- 1.05, and 0.42 +/- 0.64, and the severity of adhesion scores were
      1.71 +/- 0.91, 0.57 +/- 0.85, 0.50 +/- 0.75 for control, GnRH-ant, and GnRH-a
      groups, respectively. The extent and severity of adhesions were significantly
      lower in both GnRH-ant and GnRH-a groups when compared with the control group.
      Adhesion extent scores in the GnRH-a group were lower than in the GnRH-ant group,
      but this difference was not significant. vitronectin and u-PAR staining were
      significantly greater in both the GnRH-ant and GnRH-a groups than in the control
      group. CONCLUSION(S): GnRH-ant as well as GnRH-a reduced postoperative adhesion
      formation in a rat model. This finding was supported immunohistochemically by
      vitronectin and u-PAR staining.

PMID- 21963226
TI  - Role of manganese in neurodegenerative diseases.
AB  - Manganese (Mn) is an essential ubiquitous trace element that is required for
      normal growth, development and cellular homeostasis. Exposure to high Mn levels
      causes a clinical disease characterized by extrapyramidal symptom resembling
      idiopathic Parkinson's disease (IPD). The present review focuses on the role of
      various transporters in maintaining brain Mn homeostasis along with recent
      methodological advances in real-time measurements of intracellular Mn levels. We
      also provide an overview on the role for Mn in IPD, discussing the similarities
      (and differences) between manganism and IPD, and the relationship between alpha
      synuclein and Mn-related protein aggregation, as well as mitochondrial
      dysfunction, Mn and PD. Additional sections of the review discuss the link
      between Mn and Huntington's disease (HD), with emphasis on huntingtin function
      and the potential role for altered Mn homeostasis and toxicity in HD. We conclude
      with a brief survey on the potential role of Mn in the etiologies of Alzheimer's
      disease (AD), amyotrophic lateral sclerosis (ALS) and prion disease. Where
      possible, we discuss the mechanistic commonalities inherent to Mn-induced
      neurotoxicity and neurodegenerative disorders.

PMID- 21963229
TI  - The chromosomal risk in sperm from heterozygous Robertsonian translocation
      carriers is related to the sperm count and the translocation type.
AB  - OBJECTIVE: To study the chromosomal risk in sperm from Robertsonian translocation
      (RobT) carriers as a function of the sperm count and translocation type. DESIGN:
      Prospective study. SETTING: Departments of reproductive biology, cytogenetics,
      gynecology, and obstetrics. PATIENT(S): A total of 29 RobT patients (8
      normozoospermic and 21 oligozoospermic) and 20 46,XY patients (10 normozoospermic
      and 10 oligozoospermic). INTERVENTION(S): Sperm fluorescence in situ
      hybridization with probes for translocation malsegregation and chromosome 13, 18,
      21, X, and Y probes for studying the interchromosomal effect (ICE). MAIN OUTCOME
      MEASURE(S): Translocation malsegregation and ICE aneuploidy rates. RESULT(S): In
      RobT carriers, the sperm translocation malsegregation rate was significantly
      lower in normozoospermic patients (9.7%) than in oligozoospermic patients
      (18.0%). Considering only oligozoospermic patients, sperm malsegregation rates
      were significantly lower for rob(14;21) than for rob(13;14) (11.4% vs. 18.9%). In
      turn, the rates were significantly lower for rob(13;14) than for rare RobTs
      (18.9% vs. 25.3%). In sperm from normozoospermic RobT, an ICE was suggested by
      higher chromosome 13 and 21 aneuploidy rates than in control sperm. Conversely,
      chromosome 13 and 21 sperm aneuploidy rates were lower in oligozoospermic RobT
      patients than in oligozoospermic 46,XY patients, but higher than in control
      subjects. CONCLUSION(S): Both translocation type and sperm count influence the
      RobT malsegregation risk. Of the chromosomes analyzed (13, 18, 21, X, and Y),
      only chromosomes 13 and 21 were found to be associated with an ICE. Relative to
      the RobT effect, idiopathic alterations in spermatogenesis in 46,XY patients
      appear to be more harmful for meiosis.

PMID- 21963230
TI  - Older first-time mothers and early postpartum depression: a prospective cohort
      study of women conceiving spontaneously or with assisted reproductive
      technologies.
AB  - OBJECTIVE: To evaluate whether older first-time mothers (>=37 years) have higher
      rates of postpartum depression compared with younger first-time mothers,
      controlling for mode of conception and known risk factors for postpartum
      depression. DESIGN: Prospective cohort study. SETTING: Assisted reproductive
      technology (ART) clinics in two large Australian cities and public and private
      antenatal clinics and/or classes in the vicinity of ART clinics. PATIENT(S):
      Nulliparous women who had conceived spontaneously (n = 295) or through ART (n =
      297) in three age-groups: younger, 20 to 30 years (n = 173); middle, 31 to 36
      years (n = 214); and older, >=37 years (n = 189). INTERVENTION(S): Semistructured
      interviews and questionnaires. MAIN OUTCOME MEASURE(S): Major depressive disorder
      in the first 4 months after birth as assessed by structured diagnostic interview.
      RESULT(S): The study performed 592 complete pregnancy assessments and 541
      postpartum assessments. The prevalence of major depressive disorder was 7.9%, at
      the lower end of community rates. Neither maternal age-group nor mode of
      conception was statistically significantly related to depression. CONCLUSION(S):
      Older first-time mothers, whether conceiving through ART or spontaneously, do not
      show increased vulnerability to postnatal depression.

PMID- 21963231
TI  - Designing personal exercise monitoring employing multiple modes of delivery:
      implications from a qualitative study on heart rate monitoring.
AB  - PURPOSE: Various personal monitoring technologies have been introduced for
      supporting regular physical activity, which is of critical importance in reducing
      the risks of several chronic diseases. Recent studies suggest that combining
      multiple modes of delivery, such as text messages and mobile monitoring devices
      with web applications, holds potential for effectively supporting physical
      exercise. Of particular interest is how the functionality and content of these
      systems should be distributed across the different modes for successful outcomes.
      OBJECTIVES: The aim of this study was to: (a) investigate how users incorporate a
      system employing two modes of delivery - a wearable heart rate monitor and a web
      service - into their training and (b) to analyze benefits and limitations in
      personal exercise monitoring and how they relate to the different modes in use.
      METHODS: A qualitative field study employing diaries and semi-structured
      interviews was carried out with 30 participants who used a heart rate monitoring
      system comprising a wearable heart rate monitor, Polar FT60 and a web service,
      Polar Personal Trainer for a period of 21 days. The data were systematically
      analyzed to identify specific benefits and limitations associated with the system
      characteristics and modes as perceived by the end-users. RESULTS: The benefits
      include supporting exploratory learning, controlling target behavior, rectifying
      behaviors, motivation and logging support. The limitations are associated with
      information for validating the system, virtual coaching, task-technology fit,
      data integrity and privacy concerns. Mobile interfaces enable exploratory
      learning and controlling of target behaviors in situ, while web services can
      effectively support users' need for cognition within the early stages of adoption
      and long-term training with intelligent coaching functionality. CONCLUSIONS: This
      study explains several benefits and limitations in personal exercise monitoring.
      These can be addressed with crossmedial design, i.e., strategic distribution of
      functionality and content across modes within the system. Our findings suggest
      that personal exercise monitoring systems may be improved by more systematically
      combining mobile and web-based functionality.

PMID- 21963232
TI  - An evolutionary-fuzzy DSS for assessing health status in multiple sclerosis
      disease.
AB  - Assisted Living provides a long-term care option that combines supportive systems
      and services for monitoring and assessing the health status with activities of
      daily living and health care. Daily monitoring of the health status in subjects
      characterized by chronic and/or degenerative conditions is not possible in all
      those cases where the disease progression has to be evaluated only by a direct
      interaction between the patients and the healthcare structures on a regular
      basis, over time and for life. In this respect, this work proposes an
      evolutionary-fuzzy decision support system (DSS) for assessing the health status
      of subjects affected by multiple sclerosis (MS) during the disease progression
      over time. Such a DSS has been defined and implemented exploiting a novel
      approach devised to facilitate the design of fuzzy DSSs for medical problems. The
      approach is aimed at: (i) introducing a set of design criteria to encode the
      medical knowledge elicited from clinical experts in terms of linguistic
      variables, linguistic values and fuzzy rules with the final aim of granting the
      interpretability; (ii) defining a fuzzy inference technique to best fit the
      structure of medical knowledge and the peculiarities of the medical inference;
      (iii) defining an evolutionary technique to tune the formalized knowledge by
      optimizing the shapes of the membership functions for each linguistic variable
      involved in the rules. An experimental session has been carried out for
      evaluating, first of all, the approach on five medical databases commonly
      diffused in literature and for comparing it with other systems. After that, the
      evolutionary-fuzzy DSS for assessing MS patient's health status has been
      quantitatively evaluated on 120 patients affected by MS and compared with other
      approaches. The achieved results have shown that our approach is very effective
      on the five databases, since it provides, on average, the second highest accuracy
      when compared to eight tools. Furthermore, as far as the classification of
      multiple sclerosis lesions is considered, the proposed system has turned out to
      outperform nine popular tools.

PMID- 21963233
TI  - The co-occurrence of anxiety disorders in African American parents and their
      children.
AB  - This study examined the co-occurrence of anxiety disorders, specifically the
      relationship between parent and youth anxiety, in a community-based sample of 100
      African American parents and their biological child between the ages of 6 and 17
      years. Data were provided by both the parent and child. Parents completed the
      Anxiety Disorders Interview Schedule for DSM-IV (ADIS-IV) Client Version about
      their own experiences with anxiety and related disorders and the Parent version
      for the child's experiences. Children were administered the ADIS-IV Child version
      to assess their experiences with anxiety and related disorders. Fifty-five
      parents met criteria for at least one anxiety disorder while 34 children met
      criteria for at least one anxiety disorder. Two logistic regressions were
      subsequently conducted to predict the presence of any form of psychopathology
      from the ADIS-IV and the presence of an anxiety disorder in African American
      offspring. Results indicated that African American offspring with an anxious
      parent were 4 times more likely to meet criteria for both an anxiety disorder and
      other forms of psychopathology.

PMID- 21963234
TI  - Efficacy of mindfulness-based interventions on depressive symptoms among people
      with mental disorders: a meta-analysis.
AB  - OBJECTIVES: Depression, a common mental health problem, is projected to be the
      second leading cause of disability for adults by year 2020. Mindfulness-based
      interventions (MFIs) have been integrated into therapeutic work on depression,
      but limited systematic reviews reported their efficacy on heterogeneous groups of
      mental disorders. This meta-analysis aimed to examine the efficacy of the MFIs on
      depressive symptoms in people with various mental disorders. DESIGN: A meta
      analysis of experimental and quasi-experimental studies was undertaken. DATA
      SOURCES: Multiple search strategies were undertaken to identify published and
      unpublished studies conducted between 1995 and 2011. Electronic databases used
      were Scopus, CINAHL, PubMed, ScienceDirect, PsyINFO, Dissertation Abstract
      International, Web of Science Index, Controlled-trial.com, and
      clinicaltrials.gov. REVIEW METHODS: Data were extracted and appraised by two
      reviewers. For each study, the Quality Rating Index (QRI) and Code Sheet for
      Randomized Controlled Trials (CS-RCT) were used to assess methodological quality
      and extract relevant data respectively. Data were analysed and synthesized using
      PASW statistic 17.0 and Comprehensive Meta Analyses Software 2.0. RESULTS: Thirty
      nine studies conducted in ten countries were included and 105 effect sizes were
      calculated. Most studies utilised single group pretest-posttest quasi
      experimental design, convenience sampling, and self-reported questionnaires.
      Between-group comparisons indicated that MFIs are superior to standard care in
      reducing depressive symptoms and preventing relapse with effect sizes ranging
      from 0.11 to 1.65. Exposure-based cognitive therapy (d=2.09) appeared to be the
      most efficacious intervention, followed by mindfulness-based stress reduction
      programme (d=1.92), acceptance-based behaviour therapy (d=1.33), and stress less
      with mindfulness (d=1.31). Effect sizes were significantly associated with the
      length of intervention sessions but not related to methodological quality of
      studies. CONCLUSION: The mindfulness-based interventions are efficacious for
      alleviating depressive symptoms in adults with mental disorders. The
      interventions could be used in conjunction with other treatments in clinical
      settings.

PMID- 21963235
TI  - The effect of a simple traditional exercise programme (Baduanjin exercise) on
      sleep quality of older adults: a randomized controlled trial.
AB  - BACKGROUND: Sleep disturbance is a major problem for older adults, calling for
      the development of alternative medicine techniques to help improve sleep quality
      in this population. OBJECTIVES: The purpose of this study was to explore the
      effectiveness of a Baduanjin exercise program on sleep quality in Taiwanese
      elderly. DESIGN: A randomized controlled trial, longitudinal research design was
      employed. SETTING AND PARTICIPANTS: This study was conducted in an urban area of
      northern Taiwan. The inclusion criteria for participants were as follows: (1)
      community-dwelling older adults age 60 years or older; (2) no regular exercise
      within 6 months; (3) able to communicate; and (4) independent in self-care.
      Subjects were excluded if they had (1) depression tendency as demonstrated by the
      Chinese version of the Geriatric Depression Score of eight or higher; (2)
      impaired mobility; or (3) unstable health status. A total of 202 older people
      were screened for this study, 87 of whom were eligible according to the inclusion
      criteria. Of these, 55 completed the 12-week study. METHODS: Fifty-five
      participants were randomly assigned to the exercise group (27) or the control
      group (28). Those in the exercise group received 12 weeks of Baduanjin exercise
      training, while those in the control group had no intervention. The Pittsburg
      Sleep Quality Index was administered to subjects at four time points: before the
      intervention, and at the 4th, 8th, and 12th week after intervention. RESULTS:
      Subjects in the Baduanjin exercise group had significantly improved overall sleep
      quality, subjective sleep quality, sleep latency, sleep duration, sleep
      efficiency, and daytime dysfunction after 12 weeks of intervention (p<0.001),
      while those in control group showed no significant difference in sleep quality.
      Compared with the control group, the Baduanjin exercise group reported
      significantly better sleep quality after four weeks of intervention which was
      maintained throughout the 12-week exercise period. CONCLUSIONS: This study
      confirmed that the Baduanjin exercise program can improve sleep quality for
      Taiwanese community-dwelling older adults. We recommend application of this
      simple, gentle exercise program in older persons to improve their sleep quality.

PMID- 21963236
TI  - A modular framework for the automatic classification of chromosomes in Q-band
      images.
AB  - The manual analysis of the karyogram is a complex and time-consuming operation,
      as it requires meticulous attention to details and well-trained personnel.
      Routine Q-band laboratory images show chromosomes that are randomly rotated,
      blurred or corrupted by overlapping and dye stains. We address here the problem
      of robust automatic classification, which is still an open issue. The proposed
      method starts with an improved estimation of the chromosome medial axis, along
      which an established set of features is then extracted. The following novel
      polarization stage estimates the chromosome orientation and makes this feature
      set independent on the reading direction along the axis. Feature rescaling and
      normalizing techniques take full advantage of the results of the polarization
      step, reducing the intra-class and increasing the inter-class variances. After a
      standard neural network based classification, a novel class reassignment
      algorithm is employed to maximize the probability of correct classification, by
      exploiting the constrained composition of the human karyotype. An average 94% of
      correct classification was achieved by the proposed method on 5474 chromosomes,
      whose images were acquired during laboratory routine and comprise karyotypes
      belonging to slightly different prometaphase stages. In order to provide the
      scientific community with a public dataset, all the data we used are publicly
      available for download.

PMID- 21963237
TI  - Ectopic secretion of GHRH by a pancreatic neuroendocrine tumor associated with an
      empty sella.
AB  - Acromegaly is usually the result of a pituitary growth hormone cell-adenoma or is
      more rarely due to ectopic secretion of growth hormone releasing hormone
      (GHRH).We report the case of a 60-year-old woman with acromegaly due to a GH-RH
      secreting pancreatic tumor. Laboratory evaluation confirmed the diagnosis of
      acromegaly. Magnetic resonance imaging revealed a partial empty sella with no
      signs of adenoma. Ultrasound sonography performed for abdominal pains showed a
      calcified large heterogeneous infrahepatic mass. Computed tomography scan
      discovered a heterogeneous pancreatic head mass with a diameter of 10cm.
      Measurement of fasting plasma GHRH was performed showing a high concentration of
      604ng/L (normal 10-60). We therefore concluded that the acromegaly was caused by
      ectopic overproduction of GHRH likely due to the pancreatic tumor. The patient
      underwent a cephalic duodenopancreatectomy. Histology revealed a well
      circumscribed tumor with organoid architecture. Immunohistochemistry demonstrated
      diffuse positivity for chromogranin A, neuronal specific enolase and
      synaptophysin and negative immunoreactivity for prolactin, GH and serotonin.
      These features were concordant with a well-differentiated neuroendocrine tumor of
      the pancreas. Surgical resection of this pancreatic tumor was followed by
      significant amelioration of acromegalic signs and normalization of GHRH and GH
      levels.

PMID- 21963238
TI  - Genomic maps of long noncoding RNA occupancy reveal principles of RNA-chromatin
      interactions.
AB  - Long noncoding RNAs (lncRNAs) are key regulators of chromatin state, yet the
      nature and sites of RNA-chromatin interaction are mostly unknown. Here we
      introduce Chromatin Isolation by RNA Purification (ChIRP), where tiling
      oligonucleotides retrieve specific lncRNAs with bound protein and DNA sequences,
      which are enumerated by deep sequencing. ChIRP-seq of three lncRNAs reveal that
      RNA occupancy sites in the genome are focal, sequence-specific, and numerous.
      Drosophila roX2 RNA occupies male X-linked gene bodies with increasing tendency
      toward the 3' end, peaking at CES sites. Human telomerase RNA TERC occupies
      telomeres and Wnt pathway genes. HOTAIR lncRNA preferentially occupies a GA-rich
      DNA motif to nucleate broad domains of Polycomb occupancy and histone H3 lysine
      27 trimethylation. HOTAIR occupancy occurs independently of EZH2, suggesting the
      order of RNA guidance of Polycomb occupancy. ChIRP-seq is generally applicable to
      illuminate the intersection of RNA and chromatin with newfound precision genome
      wide.

PMID- 21963239
TI  - BRCA1 is required for postreplication repair after UV-induced DNA damage.
AB  - BRCA1 contributes to the response to UV irradiation. Utilizing its BRCT motifs,
      it is recruited during S/G2 to UV-damaged sites in a DNA replication-dependent
      but nucleotide excision repair (NER)-independent manner. More specifically, at UV
      stalled replication forks, it promotes photoproduct excision, suppression of
      translesion synthesis, and the localization and activation of replication factor
      C complex (RFC) subunits. The last function, in turn, triggers post-UV checkpoint
      activation and postreplicative repair. These BRCA1 functions differ from those
      required for DSBR.

PMID- 21963240
TI  - Social information processing in adolescents with chronic pain: my friends don't
      really understand me.
AB  - Adolescents with chronic pain are at risk for impairment in their friendships.
      They miss out on leisure activities, have increased school absence, may have
      fewer friends, are at an increased risk for victimization, and may be perceived
      by peers as less likeable. To help determine the source of these problems, the
      Social Information Processing Model (SIP) was adapted using narrative vignettes
      to determine if adolescents with chronic pain interpret friendship interactions
      differently in terms of supportive and nonsupportive behaviors compared to
      healthy peers. One hundred seven adolescents, 45 with chronic pain, completed the
      vignette questionnaire and a battery of measures. The vignette questionnaire
      included 12 vignettes to capture 3 steps in SIP processing: interpretation of
      cues, response construction, and response decision. Participants with chronic
      pain rated nonsupportive vignettes more negatively than healthy controls and
      indicated they would enact supportive behaviors towards the chronic pain
      character more often if they had been the healthy character. Age, sex, and
      internalizing measures did not significantly contribute to the findings. Chronic
      pain explained 6.5% of variance in the ratings of nonsupportive vignettes and
      10.1% of the variance in supportive behavior selection. Adolescents with chronic
      pain may interpret nonsupportive social situations with close friends as more
      distressing. The endorsement of more supportive behaviors may indicate a need
      for, and expectation of, supportive behaviors from friends. When adolescents with
      chronic pain do not perceive friends as providing support, they may avoid these
      social situations.

PMID- 21963241
TI  - An approach to localize the retinal blood vessels using bit planes and centerline
      detection.
AB  - The change in morphology, diameter, branching pattern or tortuosity of retinal
      blood vessels is an important indicator of various clinical disorders of the eye
      and the body. This paper reports an automated method for segmentation of blood
      vessels in retinal images. A unique combination of techniques for vessel
      centerlines detection and morphological bit plane slicing is presented to extract
      the blood vessel tree from the retinal images. The centerlines are extracted by
      using the first order derivative of a Gaussian filter in four orientations and
      then evaluation of derivative signs and average derivative values is performed.
      Mathematical morphology has emerged as a proficient technique for quantifying the
      blood vessels in the retina. The shape and orientation map of blood vessels is
      obtained by applying a multidirectional morphological top-hat operator with a
      linear structuring element followed by bit plane slicing of the vessel enhanced
      grayscale image. The centerlines are combined with these maps to obtain the
      segmented vessel tree. The methodology is tested on three publicly available
      databases DRIVE, STARE and MESSIDOR. The results demonstrate that the performance
      of the proposed algorithm is comparable with state of the art techniques in terms
      of accuracy, sensitivity and specificity.

PMID- 21963242
TI  - Review of salivary papers published in the British Journal of Oral &
      Maxillofacial Surgery during 2009-2010.
AB  - The management of salivary gland disease forms an appreciable part of the work
      undertaken by our specialty. Fast-track and one-stop clinics for head and neck
      lumps allow for early diagnosis of salivary gland tumours in most units, and for
      the sharing of cases between our ear, nose and throat (ENT) colleagues. The
      emphasis on benign salivary gland disease is very much on outcome after
      operation, and there have been improvements in surgical technique, particularly
      in relation to minimal dissection of salivary adenomas and sialendoscopy. This
      article continues a series of reviews, which aim to provide readers with a quick
      overview and update of recent publications in the British Journal of Oral and
      Maxillofacial Surgery (BJOMS) within a particular subspecialty.

PMID- 21963243
TI  - Colorimetric assay for the quantification of serum iodixanol concentration and
      its application on estimation of glomerular filtration rate in cattle.
AB  - A colorimetric assay used to quantify the non-ionic contrast medium iodixanol in
      sera was validated and compared with high-performance liquid chromatography. The
      application of this assay to estimate glomerular filtration rates (GFR) in cattle
      was examined. Serum iodixanol was de-iodinated by alkaline hydrolysis and the
      amount of released iodine was subsequently determined using a ceric arsenite
      method. There was a close correlation between the two methods using identical
      specimens. In clinically healthy cattle with different body weights, the
      reference value (166.3-178.8 mL/min/m(2)) based on body surface area was fairly
      stable as compared with that (2.13-3.63 mL/min/kg) based on body weight. Based on
      GFR data in healthy and renal-impaired cattle, when the GFR decreased to more
      than 60% of the reference value, serum urea nitrogen and creatinine
      concentrations increased. The colorimetric assay is a simple method for the
      estimation of GFR in cattle and requires no expensive equipment.

PMID- 21963244
TI  - Evaluation of bee venom and hyaluronic acid in the intra-articular treatment of
      osteoarthritis in an experimental rabbit model.
AB  - The aim of this study was to investigate bee venom and hyaluronic acid in the
      intra-articular treatment of osteoarthritis in an experimental rabbit model.
      Forty-five rabbits were used and they were randomly divided into three groups
      (BVI, BVII, and HA) and each group was divided to two subgroups to evaluate the
      radiologic, magnetic resonance imaging, histopathologic, and biochemical
      evaluation in post treatment second week (a) and twelfth week (b).
      Radiologically, a significant difference was observed in the HA group (P<0.05).
      The MRI evaluation of at any time in group BVI(b) was found to be different. No
      significant differences were seen between the groups, biochemically.
      Histopathologically, cellularity, and orthochromasia was evident with Safranin-O
      in the BVI(b) and BVII(a); adhesions were seen in the BVII(a) group and
      clustering of chondrocyte in the HA(b) group were found to be different.
      Consequently, intra-articular application of HA and BV for experimental model of
      osteoarthritis has no significant influence upon recovery after therapy.

PMID- 21963245
TI  - The effect of IGF-1 and FSH on the in vitro development of caprine secondary
      follicles and on the IGF-1, IGFR-I and FSHR mRNA levels.
AB  - This study verified the in vitro effects of IGF-1, FSH or both on caprine
      preantral follicle development and mRNA levels encoding IGF-1, IGFR-1 and FSHR.
      Secondary follicles were cultured for six days with FSH, IGF-1 or IGF-1+FSH. The
      results showed that IGF-1 and/or FSH addition did not influence follicular
      development for six days. The interaction between IGF-1 and FSH increased the
      mRNA levels of IGF-1 and FSHR, and FSH increased the expression of the IGFR-1
      mRNA. Thus, IGF-1 and/or FSH increased IGF-1, IGFR-1 and FSHR mRNA levels in in
      vitro cultured caprine secondary follicles, but they did not influence their
      development after six days of in vitro culture.

PMID- 21963246
TI  - Two-stage acid saccharification of fractionated Gelidium amansii minimizing the
      sugar decomposition.
AB  - Two-stage acid hydrolysis was conducted on easy reacting cellulose and resistant
      reacting cellulose of fractionated Gelidium amansii (f-GA). Acid hydrolysis of f
      GA was performed at between 170 and 200  degrees C for a period of 0-5 min, and
      an acid concentration of 2-5% (w/v, H2SO4) to determine the optimal conditions
      for acid hydrolysis. In the first stage of the acid hydrolysis, an optimum
      glucose yield of 33.7% was obtained at a reaction temperature of 190  degrees C,
      an acid concentration of 3.0%, and a reaction time of 3 min. In the second stage,
      a glucose yield of 34.2%, on the basis the amount of residual cellulose from the
      f-GA, was obtained at a temperature of 190  degrees C, a sulfuric acid
      concentration of 4.0%, and a reaction time 3.7 min. Finally, 68.58% of the
      cellulose derived from f-GA was converted into glucose through two-stage acid
      saccharification under aforementioned conditions.

PMID- 21963248
TI  - Removal of carbamazepine and sulfamethoxazole by MBR under anoxic and aerobic
      conditions.
AB  - This study reveals for the first time that near-anoxic conditions (dissolved
      oxygen, DO=0.5 mg/L) can be a favorable operating regime for the removal of the
      persistent micropollutant carbamazepine by MBR treatment. The removal
      efficiencies of carbamazepine and sulfamethoxazole by an MBR were systematically
      examined and compared under near-anoxic (DO=0.5 mg/L) and aerobic (DO>2 mg/L)
      conditions. Preliminary batch tests confirmed that sulfamethoxazole is amenable
      to both aerobic and anoxic biotransformation. However, carbamazepine-a known
      persistent compound-showed degradation only under an anoxic environment. In good
      agreement with the batch tests, during near-anoxic operation, under a high
      loading of 750 MUg/Ld, an exceptionally high removal (68+/-10%) of carbamazepine
      was achieved. In contrast, low removal efficiency (12+/-11%) of carbamazepine was
      observed during operation under aerobic conditions. On the other hand, an average
      removal efficiency of 65% of sulfamethoxazole was achieved irrespective of the DO
      concentrations.

PMID- 21963249
TI  - Propagated fixed-bed mixed-acid fermentation: Part I: Effect of volatile solid
      loading rate and agitation at high pH.
AB  - Countercurrent fermentation is a high performing process design for mixed-acid
      fermentation. However, there are high operating costs associated with moving
      solids, which is an integral component of this configuration. This study
      investigated the effect of volatile solid loading rate (VSLR) and agitation in
      propagated fixed-bed fermentation, a configuration which may be more commercially
      viable. To evaluate the role of agitation on fixed-bed configuration performance,
      continuous mixing was compared with periodic mixing. VSLR was also varied and not
      found to affect acid yields. However, increased VSLR and liquid retention time
      did result in higher conversions, productivity, acid concentrations, but lower
      selectivities. Agitation was demonstrated to be important for this fermentor
      configuration, the periodically-mixed fermentation had the lowest conversion and
      yields. Operating at a high pH (~9) contributed to the high selectivity to acetic
      acid, which might be industrially desirable but at the cost of lower yield
      compared to a neutral pH.

PMID- 21963251
TI  - Please turn off the lights: the effectiveness of visual prompts.
AB  - Two early studies showed that visual prompts can be effectively used to encourage
      people to turn off the lights in unoccupied classrooms, but they were
      methodologically limited. The current study used an ABAB-B design with an 11-week
      follow-up to investigate whether two different visual prompts (large and small
      signs) could be employed to increase "lights off" behaviour in 17 unoccupied
      washrooms. The odds were eight times higher that lights would be turned off in
      washrooms with signs than washrooms without, and large signs trended toward being
      more effective than small signs. Signs in washrooms with windows appeared to be
      the most effective, but this finding merits further research. Behaviour change
      persisted throughout the follow-up period, but reactance by a single washroom
      user resulted in some signs being removed. Compared to previous research, the
      current study used an improved methodology with a larger number of study sites.
      This study demonstrated that a simple, well-designed sign can effectively
      encourage energy conservation.

PMID- 21963250
TI  - A field intervention examining the impact of an office ergonomics training and a
      highly adjustable chair on visual symptoms in a public sector organization.
AB  - OBJECTIVE: Examine the effect of a multi-component office ergonomics intervention
      on visual symptom reductions. METHODS: Office workers were assigned to either a
      group receiving a highly adjustable chair with office ergonomics training (CWT),
      a training-only group (TO) or a control group (C). A work environment and health
      questionnaire was administered 2 and 1 month(s) pre-intervention and 3, 6, and 12
      months post-intervention. Multi-level statistical models tested hypotheses.
      RESULTS: The CWT intervention lowered daily visual symptoms (p < 0.01) post
      intervention. The TO group did not significantly differ from the control group.
      The CWT group differed significantly from the TO group (p = 0.01) post
      intervention. CONCLUSION: Workers who received a highly adjustable chair and
      office ergonomics training had reduced visual symptoms and the effect was
      maintained through twelve months post-intervention. The lack of a training-only
      group effect supports implementing training in conjunction with the highly
      adjustable chair to reduce visual symptoms.

PMID- 21963252
TI  - Developing a clinical pediatric interventional practice: a joint clinical
      practice guideline from the Society of Interventional Radiology and the Society
      for Pediatric Radiology.

PMID- 21963253
TI  - Cloning, characterization and gene expression of a metallothionein isoform in the
      edible cockle Cerastoderma edule after cadmium or mercury exposure.
AB  - Metallothionein (MT) genes encode crucial metal-binding proteins ubiquitously
      expressed in living organisms and which play important roles in homeostasis of
      essential metals and detoxification processes. Here, the molecular organization
      of the first metallothionein gene of the edible cockle Cerastoderma edule and its
      expression after cadmium (Cd) or mercury (Hg) exposures were determined. The
      resulting sequence (Cemt1) exhibits unusual features. The full length cDNA
      encodes a protein of 73 amino acids with nine classical Cys-X((1-3))-Cys motifs,
      but also one Cys-Cys not generally found in molluscan MT. Moreover,
      characterization of the molecular organization of the Cemt1 gene revealed two
      different alleles (A1 and A2) with length differences due to large deletion
      events in their intronic sequences involving direct Short Interspersed repeated
      Elements (SINE), while their exonic sequences were identical. To our knowledge,
      such large excision mechanisms have never before been reported in a bivalve gene
      sequence. After 10 days of Cd exposure at environmentally relevant doses,
      quantitative real-time PCR revealed a strong induction of Cemt1 in gills of C.
      edule. Surprisingly, neither induction of the Cemt1 gene nor of MT protein was
      shown after Hg exposure, despite the fact that this organism is able to
      bioaccumulate a high amount of this trace metal which is theoretically one of the
      most powerful inducers of MT biosynthesis.

PMID- 21963254
TI  - [Inflammatory pseudotumor in a five-year-old girl].
AB  - Inflammatory pseudotumor is the most common primary lung mass in children. In
      many cases, it mimics organizing pneumonia on imaging tests. Another site often
      affected by inflammatory pseudotumors is the orbit, although they can be found in
      any part of the body. Inflammatory pseudotumors are rare and quasi-neoplastic, as
      radiologically and clinically they behave like malignant tumors. Consensus about
      their pathogenesis, natural history, imaging findings, and treatment options has
      yet to be reached.

PMID- 21963247
TI  - Transcriptome analysis of an oil-rich race B strain of Botryococcus braunii (BOT
      22) by de novo assembly of pyrosequencing cDNA reads.
AB  - To gain genetic insights into the biosynthesis of botryococcene oils in
      Botryococcus braunii race B, a transcriptome dataset of the BOT-22 strain
      containing 27,427 non-redundant sequences assembled from 209,429 complementary
      DNA reads was obtained via high-throughput 454 sequencing. Relatively reliable
      prediction of the gene product was feasible for 725 non-redundant sequences based
      on homology to previously characterized database sequences. Regarding the
      botryococcene oil biosynthesis, genes putatively associated with the mevalonate
      independent isoprenoid biosynthesis pathway were retrieved, while no genes were
      found for the mevalonate pathway, suggesting that botryococcenes are
      biosynthesized through the mevalonate-independent pathway in B. braunii. All
      transcriptome sequences have been deposited in the GenBank/EMBL/DDBJ database.

PMID- 21963255
TI  - [Imaging in epilepsy: functional studies].
AB  - Neuroimaging studies play a fundamental role in the diagnosis and evaluation of
      epilepsy. Technological advances in neuroimaging techniques have made it possible
      to obtain functional as well as structural information. The pathophysiology of
      epilepsy consists of an abnormal increase in cerebral activity that can be
      appreciated on neuroimaging techniques like functional magnetic resonance imaging
      (fMRI), PET, and SPECT. In patients with epilepsy that is refractory to drug
      therapy, the main aim of surgery is to control seizures and thus to improve the
      quality of life. In the preoperative workup of these patients, fMRI has an
      increasingly important role, evaluating the location of functional areas that
      must be safeguarded during surgery.

PMID- 21963256
TI  - Network simulation modeling of equine infectious anemia in the non-racehorse
      population in Japan.
AB  - An equine infectious anemia (EIA) transmission model was developed by
      constructing a network structure of horse movement patterns in a non-racehorse
      population. This model was then used to evaluate the effectiveness and efficiency
      of several EIA surveillance strategies. Because EIA had not been detected in
      Japan since 1993, it was appropriate to review the current surveillance strategy,
      which aims to eradicate EIA by intensive testing, and to consider alternative
      strategies suitable for the current EIA status in Japan. The non-racehorse
      population was divided into four sectors based on horse usage: the equestrian
      sector, private owner sector, exhibition sector, and fattening sector. To
      evaluate the risk of disease spread within and between sectors accompanied by
      horse movements, a stochastic individual-based network model was developed based
      on a previous survey of horse movement patterns. Surveillance parameters such as
      targeting sectors and frequency of testing were added into the model to compare
      surveillance strategies. The disease spread heterogeneously among sectors.
      Infection occurred mainly in the equestrian sector; the infection was less
      disseminated in other sectors. Therefore, we considered that the equestrian
      sector posed a higher risk of disease dissemination within and between sectors
      through horse movements. However, surveillance strategies targeting only the
      equestrian sector were not effective enough for early detection of the disease.
      Alternatively, targeting horses that moved permanently and those in the private
      owner sector in addition to the equestrian sector is recommended to achieve
      effectiveness equivalent to that of the current surveillance. In terms of
      surveillance efficacy, by increasing the testing interval (once yearly to once
      every 3 years), this testing scheme could reduce the number of tested horses to
      44% of the current surveillance, while maintaining almost equivalent
      effectiveness. Intensive strategies targeting high-risk populations are
      considered to enhance effectiveness and efficiency of surveillance. The approach
      in this study may be helpful in the decision-making process that is involved in
      setting up strategies for risk-based surveillance.

PMID- 21963257
TI  - On the validity of remember-know judgments: evidence from think aloud protocols.
AB  - The use of remember-know judgments to assess subjective experience associated
      with memory retrieval, or as measures of recollection and familiarity processes,
      has been controversial. In the current study we had participants think aloud
      during study and provide verbal reports at test for remember-know and confidence
      (i.e., sure-probably) judgments. Results indicated that the vast majority of
      remember judgments for studied items were associated with recollection from study
      (87%), but this correspondence was less likely for high-confidence judgments
      (72%). Instead, high-confidence judgments were more likely than remember
      judgments to be associated with incorrect recollection and a lack of
      recollection. Know judgments were typically associated with a lack of
      recollection (62%), but still included recollection from the study context (33%).
      Thus, although remember judgments provided fairly accurate assessments of
      retrieval including contextual details, know judgments did not provide accurate
      assessments of retrieval lacking contextual details.

PMID- 21963258
TI  - Integrating autoimmune risk loci with gene-expression data identifies specific
      pathogenic immune cell subsets.
AB  - Although genome-wide association studies have implicated many individual loci in
      complex diseases, identifying the exact causal alleles and the cell types within
      which they act remains greatly challenging. To ultimately understand disease
      mechanism, researchers must carefully conceive functional studies in relevant
      pathogenic cell types to demonstrate the cellular impact of disease-associated
      genetic variants. This challenge is highlighted in autoimmune diseases, such as
      rheumatoid arthritis, where any of a broad range of immunological cell types
      might potentially be impacted by genetic variation to cause disease. To this end,
      we developed a statistical approach to identify potentially pathogenic cell types
      in autoimmune diseases by using a gene-expression data set of 223 murine-sorted
      immune cells from the Immunological Genome Consortium. We found enrichment of
      transitional B cell genes in systemic lupus erythematosus (p = 5.9 * 10(-6)) and
      epithelial-associated stimulated dendritic cell genes in Crohn disease (p = 1.6 *
      10(-5)). Finally, we demonstrated enrichment of CD4+ effector memory T cell genes
      within rheumatoid arthritis loci (p < 10(-6)). To further validate the role of
      CD4+ effector memory T cells within rheumatoid arthritis, we identified 436 loci
      that were not yet known to be associated with the disease but that had a
      statistically suggestive association in a recent genome-wide association study
      (GWAS) meta-analysis (p(GWAS) < 0.001). Even among these putative loci, we noted
      a significant enrichment for genes specifically expressed in CD4+ effector memory
      T cells (p = 1.25 * 10(-4)). These cell types are primary candidates for future
      functional studies to reveal the role of risk alleles in autoimmunity. Our
      approach has application in other phenotypes, outside of autoimmunity, where many
      loci have been discovered and high-quality cell-type-specific gene expression is
      available.

PMID- 21963259
TI  - XX ovarian dysgenesis is caused by a PSMC3IP/HOP2 mutation that abolishes
      coactivation of estrogen-driven transcription.
AB  - XX female gonadal dysgenesis (XX-GD) is a rare, genetically heterogeneous
      disorder characterized by lack of spontaneous pubertal development, primary
      amenorrhea, uterine hypoplasia, and hypergonadotropic hypogonadism as a result of
      streak gonads. Most cases are unexplained but thought to be autosomal recessive.
      We elucidated the genetic basis of XX-GD in a highly consanguineous Palestinian
      family by using homozygosity mapping and candidate-gene and whole-exome
      sequencing. Affected females were homozygous for a 3 bp deletion (NM_016556.2,
      c.600_602del) in the PSMC3IP gene, leading to deletion of a glutamic acid residue
      (p.Glu201del) in the highly conserved C-terminal acidic domain. Proteasome 26S
      subunit, ATPase, 3-Interacting Protein (PSMC3IP)/Tat Binding Protein Interacting
      Protein (TBPIP) is a nuclear, tissue-specific protein with multiple functions. It
      is critical for meiotic recombination as indicated by the known role of its yeast
      ortholog, Hop2. Through the C terminus (not present in yeast), PSMC3IP also
      coactivates ligand-driven transcription mediated by estrogen, androgen,
      glucocorticoid, progesterone, and thyroid nuclear receptors. In cell lines, the
      p.Glu201del mutation abolished PSMC3IP activation of estrogen-driven
      transcription. Impaired estrogenic signaling can lead to ovarian dysgenesis both
      by affecting the size of the follicular pool created during fetal development and
      by failing to counteract follicular atresia during puberty. PSMC3IP joins
      previous genes known to be mutated in XX-GD, the FSH receptor, and BMP15,
      highlighting the importance of hormonal signaling in ovarian development and
      maintenance and suggesting a common pathway perturbed in isolated XX-GD. By
      analogy to other XX-GD genes, PSMC3IP is also a candidate gene for premature
      ovarian failure, and its role in folliculogenesis should be further investigated.

PMID- 21963260
TI  - Reduction of carbon dioxide on jet spray formed titanium dioxide surfaces.
AB  - The photocatalytic reduction of carbon dioxide (CO(2)) on jet spray formed
      titanium dioxide (TiO(2)) was studied using light-emitting diode (LED)
      illumination centred at a wavelength of 388 nm. In addition, the photocatalytic
      reduction of CO(2) under soft X-ray irradiation was also studied. Specifically,
      the experiments examined the reduction of CO(2) in a gaseous and liquid-gas
      system using residual gas analysis mass spectrometry. A photochemical reduction
      of CO(2) was observed over a course of 250 min, with transformation to a major
      product, C(2)H(3)O(-) (ethenolate), until equilibrium was reached. The product
      was observed to be surface stabilised, with it reverting back to CO(2) over the
      course of 100 min without illumination. A proposed free radical mechanism is
      presented for the formation of this product. A similar effect to that of UV
      illumination is also observed to occur under the influence of soft X-rays, which
      presents a potentially significant alternative method for the activation of
      TiO(2).

PMID- 21963261
TI  - Rhizodegradation gradients of phenanthrene and pyrene in sediment of mangrove
      (Kandelia candel (L.) Druce).
AB  - A greenhouse experiment was conducted to evaluate degradation gradient of spiked
      phenanthrene (Ph, 10 mg kg(-1)) and pyrene (Py, 10 mg kg(-1)) in rhizosphere of
      mangrove Kandelia candel (L.) Druce. Rhizosphere model system was set up using a
      self-design laminar rhizoboxes which divided into eight separate compartments at
      various distances from the root surface. After 60 days of plant growth, presence
      of the plant significantly enhanced the dissipation of Ph (47.7%) and Py (37.6%)
      from contaminated sediment. Higher degradation rates of the PAHs were observed at
      3mm from the root zone (56.8% Ph and 47.7% Py). The degradation gradient followed
      the order: near rhizosphere>root compartment>far-rhizosphere soil zones for both
      contaminants where mangrove was grown. Contribution of direct plant uptake and
      accumulation of Ph and Py were very low compared to the plant enhanced
      dissipation. By contrast, plant-promoted biodegradation was the predominant
      contribution to the remediation enhancement. The correlation analysis indicates a
      negative relation between biological activities (microbial biomass carbon,
      dehydrogenase, urease, and phosphatase activity) and residual concentrations of
      Ph and Py in planted soils. Our results suggested that mangrove rhizosphere was
      effective in promoting the depletion of aromatic hydrocarbons in contaminated
      sediments.

PMID- 21963262
TI  - Complete transection of the main bile duct: minimally invasive treatment with an
      endoscopic-radiologic rendezvous.
AB  - BACKGROUND: Complete transection of the common bile duct (CBD) is a dramatic and
      often extremely difficult-to-repair event after surgery. Abdominal biliary fluid
      collection or jaundice is the initial symptom, and ERCP is the determinant for
      diagnosis. OBJECTIVE: To evaluate the safety and efficacy of a combined
      endoscopic-radiologic technique for the reconstruction of the CBD. DESIGN: Single
      center retrospective study. SETTING: Tertiary-care center for biliary surgery.
      PATIENTS: This study involved 22 patients with complete transection of the CBD
      after cholecystectomy. INTERVENTION: A guidewire is passed in the subhepatic
      space through the endoscopic approach. A snare loop is advanced from the
      percutaneous entry site to catch the free end of the wire and then pulled outside
      the body: a percutaneous biliary-duodenal (PTBD) drainage is put in place. After
      a new contralateral PTBD, 4 plastic stents are inserted. The stents are removed
      endoscopically after 8 to 12 months. MAIN OUTCOME MEASUREMENTS: Success of the
      rendezvous maneuver, patient recovery, and patient mortality. RESULTS: After a
      mean follow-up period of 4 years, 16 patients are asymptomatic. Two patients are
      still under treatment, and 4 patients underwent surgery, as was the surgeon's
      choice. LIMITATIONS: Single-center, retrospective study with a small population.
      CONCLUSION: Interruption of the biliary tree does not represent an indication for
      an often-difficult surgical treatment, because the CBD is often thin in the
      presence of biliary peritonitis. However, the condition can be treated with a
      rendezvous technique. Surgery can be performed in elective conditions or
      completely avoided when conservative therapy is selected.

PMID- 21963263
TI  - Linoleic acid recommendations--A house of cards.

PMID- 21963264
TI  - In vivo reflectance confocal microscopy of the skin: a noninvasive means of
      assessing body cystine accumulation in infantile cystinosis.
AB  - BACKGROUND: Patients with infantile nephropathic cystinosis have progressive
      accumulation of cystine in tissues leading to delayed extrarenal complications.
      No simple tool is available to evaluate the level of body cystine accumulation.
      OBJECTIVE: We sought to determine the value of in vivo reflectance confocal
      microscopy of the skin in patients with infantile nephrogenic cystinosis.
      METHODS: Nine patients and control subjects were recruited for this study. Images
      were acquired by means of a near-infrared reflectance confocal laser scanning
      microscope. RESULTS: Scattered bright particles within the papillary dermis were
      observed in all patients but not in control subjects. The density of particles
      ranged from numerous (+++) to very few (+/-) and their distribution was
      heterogeneous. Electron microscopy confirmed that these particles corresponded to
      cystine crystal deposits within dermal fibroblasts. The density of cystine
      crystals within the dermis was greater in older patients, in patients with a high
      leukocyte cystine concentration, and with delayed cysteamine therapy. There was
      no correlation between the density of cystine deposits and renal disease or
      hypopigmentation but high levels of deposition occurred in association with
      extrarenal manifestations. LIMITATIONS: This is a preliminary study on a small
      sample of patients. Repeated examination and longer follow-up is necessary.
      CONCLUSION: In vivo reflectance confocal microscopy of the skin appears to be a
      noninvasive means of assessing body cystine accumulation in infantile cystinosis
      and could be used as a complementary marker of treatment response in addition to
      leukocyte cystine measurement.

PMID- 21963265
TI  - Clinical characteristics of a large cohort of patients with scleritis and
      episcleritis.
AB  - OBJECTIVE: To evaluate the demographic characteristics, clinical features, ocular
      complications, and disease associations of patients with scleritis and
      episcleritis; as well as to delineate the risk factors for decreased vision in
      patients with scleritis. DESIGN: Retrospective case series. PARTICIPANTS: Five
      hundred patients with scleritis and 85 patients with episcleritis. METHODS: The
      electronic health records of 500 patients with scleritis and 85 patients with
      episcleritis seen at 2 tertiary referral centers were reviewed and their clinical
      features were studied. MAIN OUTCOME MEASURES: Clinical features (pain, scleral
      inflammation), ocular complications (decrease in vision, anterior uveitis,
      peripheral ulcerative keratitis, ocular hypertension), and disease associations.
      RESULTS: In a series of 585 patients, 500 patients had scleritis (85.5%) and 85
      patients had episcleritis (14.2%). Ocular complications were more frequent
      overall in patients with scleritis versus in those with episcleritis (45.0% vs.
      19.0%), including decrease in vision (15.8% vs. 2.3%), anterior uveitis (26.4%
      vs. 16.5%), peripheral ulcerative keratitis (7.4% vs. 0%), and ocular
      hypertension (14.2% vs. 3.5%; P<0.0001 for each). Disease association was
      observed in 35.8% of patients with scleritis versus 27.1% of episcleritis
      patients, including connective tissue or vasculitic diseases in 24.8% versus
      15.3%, respectively. Scleritis preceded systemic disease diagnosis in 38.7% of
      patients. Ocular complications (90.0%) and disease association (80.0%) occurred
      most often in patients with necrotizing scleritis (P<0.0001 for each). Risk
      factors for decrease in vision in patients with scleritis included necrotizing
      scleritis (odds ratio [OR], 6.63; P<0.001), posterior scleritis (OR, 2.33; P =
      0.042), degree of scleral inflammation of more than 2+ (range, 0-4+; OR, 3.60;
      P<0.001), anterior uveitis (OR, 1.78; P = 0.033), ocular hypertension (OR, 3.19;
      P<0.001), and associated disease (OR, 2.66; P<0.001), mainly infectious (OR,
      4.44; P<0.001). CONCLUSIONS: Scleritis is associated more often with ocular
      complications than episcleritis, and necrotizing scleritis is the type of
      scleritis most often associated with ocular complications and disease
      association. Risk factors for decrease in vision in patients with scleritis
      include necrotizing scleritis, posterior scleritis, scleral inflammation of more
      than 2+, anterior uveitis, ocular hypertension, and associated infectious
      disease. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial
      interest in any materials discussed in this article.

PMID- 21963266
TI  - Atropine for the treatment of childhood myopia: safety and efficacy of 0.5%,
      0.1%, and 0.01% doses (Atropine for the Treatment of Myopia 2).
AB  - PURPOSE: Our previous study, Atropine for the Treatment of Myopia 1 (ATOM1),
      showed that atropine 1% eyedrops were effective in controlling myopic progression
      but with visual side effects resulting from cycloplegia and mydriasis. The aim of
      this study was to compare efficacy and visual side effects of 3 lower doses of
      atropine: 0.5%, 0.1%, and 0.01%. DESIGN: Single-center, double-masked, randomized
      study. PARTICIPANTS: A total of 400 children aged 6-12 years with myopia of at
      least -2.0 diopters (D) and astigmatism of -1.50 D or less. INTERVENTION:
      Children were randomly assigned in a 2:2:1 ratio to 0.5%, 0.1%, and 0.01%
      atropine to be administered once nightly to both eyes for 2 years. Cycloplegic
      refraction, axial length, accommodation amplitude, pupil diameter, and visual
      acuity were noted at baseline, 2 weeks, and then every 4 months for 2 years. MAIN
      OUTCOME MEASURES: Myopia progression at 2 years. Changes were noted and
      differences between groups were compared using the Huber-White robust standard
      error to allow for data clustering of 2 eyes per person. RESULTS: The mean myopia
      progression at 2 years was -0.30+/-0.60, -0.38+/-0.60, and -0.49+/-0.63 D in the
      atropine 0.5%, 0.1%, and 0.01% groups, respectively (P=0.02 between the 0.01% and
      0.5% groups; between other concentrations P > 0.05). In comparison, myopia
      progression in ATOM1 was -1.20+/-0.69 D in the placebo group and -0.28+/-0.92 D
      in the atropine 1% group. The mean increase in axial length was 0.27+/-0.25,
      0.28+/-0.28, and 0.41+/-0.32 mm in the 0.5%, 0.1%, and 0.01% groups, respectively
      (P < 0.01 between the 0.01% and 0.1% groups and between the 0.01% and 0.5%
      groups). However, differences in myopia progression (0.19 D) and axial length
      change (0.14 mm) between groups were small and clinically insignificant. Atropine
      0.01% had a negligible effect on accommodation and pupil size, and no effect on
      near visual acuity. Allergic conjunctivitis and dermatitis were the most common
      adverse effect noted, with 16 cases in the 0.1% and 0.5% atropine groups, and no
      cases in the 0.01% group. CONCLUSIONS: Atropine 0.01% has minimal side effects
      compared with atropine at 0.1% and 0.5%, and retains comparable efficacy in
      controlling myopia progression.

PMID- 21963267
TI  - Choroidal abnormalities detected by near-infrared reflectance imaging as a new
      diagnostic criterion for neurofibromatosis 1.
AB  - OBJECTIVE: To investigate in a large sample of consecutive patients with
      neurofibromatosis type 1 (NF1) the possibility of including the presence of
      choroidal abnormalities detected by near-infrared reflectance (NIR) as a new
      diagnostic criterion for NF1. DESIGN: Cross-sectional evaluation of a diagnostic
      test. PARTICIPANTS AND CONTROLS: Ninety-five consecutive adult and pediatric
      patients (190 eyes) with NF1, diagnosed based on the National Institutes of
      Health (NIH) criteria. Controls included 100 healthy age- and gender-matched
      control subjects. METHODS: Confocal scanning laser ophthalmoscopy was performed
      for each subject, investigating the presence and the number of choroidal
      abnormalities. MAIN OUTCOME MEASURES: Sensitivity, specificity, and diagnostic
      accuracy for the different cutoff values of the criterion choroidal nodules
      detected by NIR compared with the NIH criteria. RESULTS: Choroidal nodules
      detected by NIR imaging were present in 79 (82%) of 95 of the NF1 patients,
      including 15 (71%) of the 21 NF1 pediatric patients. Similar abnormalities were
      present in 7 (7%) of 100 healthy subjects, including 2 (8%) of the 25 healthy
      pediatric subjects. The highest accuracy was obtained at the cutoff value of 1.5
      choroidal nodules detected by NIR imagery. Sensitivity and specificity of the
      examination at the optimal cutoff point were 83% and 96%, respectively.
      Diagnostic accuracy was 90% in the overall population and 83% in the pediatric
      population. Both of these values were in line with the most common NIH diagnostic
      criteria. CONCLUSIONS: Choroidal abnormalities appearing as bright patchy nodules
      detected by NIR imaging frequently occurred in NF1 patients. The present study
      shows that NIR examination to detect choroidal involvement should be considered
      as a new diagnostic criterion for NF1.

PMID- 21963268
TI  - Amblyopia prevalence and risk factors in Australian preschool children.
AB  - PURPOSE: To determine the prevalence of and factors associated with amblyopia in
      a sample of Australian preschool children. DESIGN: Population-based, cross
      sectional study. PARTICIPANTS: The Sydney Paediatric Eye Disease Study examined
      2461 (73.8% participation) children aged between 6 and 72 months from 2007 to
      2009. METHODS: Visual acuity (VA) was assessed in children aged >= 30 months
      using the Electronic Visual Acuity system, and a subset using the logarithm of
      the minimum angle of resolution chart. Amblyopia was categorized into unilateral
      and bilateral subtypes: Unilateral amblyopia was defined as a 2-line difference
      in reduced VA between the 2 eyes, in addition to strabismus, anisometropia,
      and/or visual axis obstruction; bilateral amblyopia was defined as bilateral
      reduced VA with either bilateral visual axis obstruction or significant bilateral
      ametropia. Information on ethnicity, birth parameters, and measures of
      socioeconomic status were collected in questionnaires completed by parents. MAIN
      OUTCOME MEASURES: Amblyopia. RESULTS: We included 1422 children aged 30 to 72
      months, of whom 27 (1.9%) were found to have amblyopia or suspected amblyopia.
      Mean spherical equivalent for the amblyopic eyes was +3.57 diopters, with a mean
      VA of 20/50. Only 3 of the 27 amblyopic children had previous diagnoses or
      treatments for amblyopia. In regression analysis controlling for age, gender, and
      ethnicity, amblyopia was significantly associated with hyperopia (odds ratio
      [OR], 15.3; 95% confidence interval [CI], 6.5-36.4), astigmatism (OR, 5.7; 95%
      CI, 2.5-12.7), anisometropia (OR, 27.8; 95% CI, 11.2-69.3), and strabismus (OR,
      13.1; 95% CI, 4.3-40.4). There were no significant associations of amblyopia with
      low birthweight (<2500 g), preterm birth (<37 weeks), maternal smoking, age,
      gender, ethnicity, or measures of socioeconomic status (all P>0.05). CONCLUSIONS:
      Amblyopia was found in 1.9% of this Australian preschool sample, which is
      comparable with prevalence rates reported by other recent studies in preschool
      children. Refractive errors, particularly significant hyperopia and astigmatism,
      in addition to anisometropia and strabismus, were the major amblyogenic factors.
      There was a low amblyopia detection rate in this preschool population, which
      suggests that different strategies are required to improve current vision
      screening strategies in preschoolers. FINANCIAL DISCLOSURE(S): The authors have
      no proprietary or commercial interest in any of the materials discussed in this
      article.

PMID- 21963269
TI  - Global study of viral diarrhea in hospitalized children in Spain: results of
      structural surveillance of viral gastroenteritis net work (VIGESS-net) 2006-2008.
AB  - BACKGROUND AND OBJECTIVES: Detection and characterization of gastroenteritis
      cases (viruses) was conducted during eleven years through the surveillance VIGESS
      net, which was created in an effort to conduct a structured surveillance of
      rotavirus genotypes co-circulating in Spain. STUDY DESIGN AND RESULTS: This phase
      includes the study of 2048 fecal samples from children <5 years old, hospitalized
      in fifteen different hospitals throughout Spain from March 2006 to March 2008. Of
      them, 821 (40.1%) samples were rotavirus positive. Rotavirus was identified as
      the only etiological agent in 694 (33.9%) cases and in 127 (6.2%) was found as
      coinfection with other enteric viruses, mainly with noroviruses. Predominant G
      genotypes detected were G1 (49.8%) followed by G9 (32.9%), G3 (2.6%), G8 (1.0%),
      G4 (0.4%), G6 (0.2%) and G12 (0.2%). The G2 was encountered in 3.2% of cases.
      Rotavirus mixed G-types infections occurred in 3.9% of cases. The main G/P
      combinations were G1P[8] (51.9%) and G9P[8] (35.6%), which predominates
      alternatively in the first and second period of the study. More rare combinations
      occur in less than 7.4% of cases. CONCLUSION: The diversity of rotavirus
      circulating strains suggests to maintain a surveillance system through different
      regions of the country.

PMID- 21963270
TI  - Electrochemical oxidation of berberine and mass spectrometric identification of
      its oxidation products.
AB  - Electrochemical oxidation of the isoquinoline alkaloid berberine in aqueous
      medium was studied by cyclic and differential pulse voltammetry at a glassy
      carbon electrode (GCE). Two anodic peaks of the quaternary form of berberine were
      observed at +1.2V and +1.4V (vs. SCE) in acidic and neutral solutions. When the
      anodic polarization exceeded the value of +1.1 V, the redox active film is formed
      on the GCE surface. The formation of adsorbed film was well-documented by
      quasireversible redox couple at +0.25 V which was studied in redox cycling
      experiments. In alkaline medium, a new anodic peak at +0.5 V appeared due to
      oxidation of berberine pseudobase to 8-oxoberberine. Solutions of berberine at
      different pH were subjected to controlled potential electrolysis on platinum
      gauze electrode and analyzed using liquid chromatography (HPLC) equipped with
      electrospray ionization/quadrupole time-of-flight mass spectrometry. The main
      water soluble monomeric product of berberine oxidation under physiological-near
      experimental conditions, OP1, was identified as demethyleneberberine cation (2,3
      dihydroxy-9,10-dimethoxy-5,6-dihydroisoquinolino[3,2-a]isoquinolin-7-ium).

PMID- 21963271
TI  - [Emerging Acinetobacter baumannii infections and factors favouring their
      occurrence].
AB  - During the last decade, Acinetobacter baumannii (AB) has been increasingly
      responsible for infections occurring in three particular contexts (in terms of
      patients and environment). Community AB pneumonia is severe infections, mainly
      described around the Indian Ocean, and which mainly concern patients with major
      co-morbidities. AB is also responsible for infections occurring among soldiers
      wounded in action during operations conducted in Iraq or Afghanistan. Lastly,
      this bacterium is responsible for infections occurring among casualties from
      natural disasters like earthquakes and tsunamis. Those infections are often due
      to multidrug-resistant strains, which can be implicated in nosocomial outbreaks
      when patients are hospitalized in a local casualty department or during their
      repatriation thereafter. The source of the contaminations which lead to AB
      infections following injuries (warfare or natural disasters) is still poorly
      known. Three hypotheses are usually considered: a contamination of wounds with
      environmental bacteria, a wound contamination from a previous cutaneous or
      oropharyngeal endogenous reservoir, or hospital acquisition. The implication of
      telluric or agricultural primary reservoirs in human AB infections is a common
      hypothesis which remains to be demonstrated by further specifically designed
      studies.

PMID- 21963272
TI  - Ultrasound-assisted ionic liquid dispersive liquid-liquid microextraction coupled
      with high performance liquid chromatography for sensitive determination of trace
      celastrol in urine.
AB  - Ultrasound-assisted ionic liquid dispersive liquid-liquid microextraction (UA IL
      DLLME) coupled with high-performance liquid chromatography (HPLC) has been
      developed for the determination of celastrol in human urine samples. In the
      microextraction procedure, ionic liquid (IL) was used as extraction solvent and
      dispersed into the aqueous sample solution as fine droplets by means of
      dispersive solvent and ultrasonication which promoted the analyte to migrate into
      IL phase more easily. Several important parameters affecting the extraction
      efficiency were studied and optimized, including the type and volume of
      extraction solvent and dispersive solvent, sample pH, ultrasonication time,
      cooling time, centrifugation time and salting-out effect. Under the optimized
      conditions, 110-fold enrichment factor was obtained and the limit of detection
      (LOD) was 1.6 MUg/L at a signal-to-noise ratio of 3. The calibration curve was
      linear over the range of 10-1000 MUg/L for celastrol in human urine sample, with
      a correlation coefficient of 0.9980. Intra- and inter-assay precision were 0.43%
      and 2.78%, respectively. The proposed method was successfully applied to the real
      human urine samples and good spiked recoveries in the range of 93.2-109.3% were
      obtained.

PMID- 21963273
TI  - Preparation of high purity biphenyl cyclooctene lignans from Schisandra extract
      by ion exchange resin catalytic transformation combined with macroporous resin
      separation.
AB  - In this study, ester-bond biphenyl cyclooctene lignans were efficiently
      hydrolytically degraded into free biphenyl cyclooctene lignans by ion exchange
      resin transformation and simultaneous removal of impurities by macroporous resin.
      The OH-type strongly basic anion exchange resin 201*7 was the best one, and the
      dynamic hydrolysis efficiency was 146.7+/-5.0%. HPD5000 macroporous resin, which
      offered higher adsorption and desorption capacities and faster adsorption than
      other resins. The purity of free biphenyl cyclooctene lignans in the product
      increased from 5.14+/-0.24% to 79.67+/-0.0.67%. After dynamic catalytic
      transformation by 201*7 resin combined with purification of HPD5000 resin, the
      yield and the purity of free biphenyl cyclooctene lignans in the product were
      132.1+/-4.7% and 80.91+/-3.53%, respectively.

PMID- 21963274
TI  - Depletion of highly abundant proteins in blood plasma by ammonium sulfate
      precipitation for 2D-PAGE analysis.
AB  - Ammonium sulfate precipitation (ASP) was explored as a method for depleting some
      highly abundant proteins from blood plasma, in order to reduce the dynamic range
      of protein concentration and to improve the detection of low abundance proteins
      by 2D-PAGE. 40% ammonium sulfate saturation was chosen since it allowed depleting
      39% albumin and 82% alpha-1-antitrypsin. ASP-depletion showed high
      reproducibility in 2D-PAGE analysis (4.2% variation in relative abundance of
      albumin), similar to that offered by commercial affinity-depletion columns.
      Besides, it allowed detecting 59 spots per gel, very close to the number of spots
      detected in immuno-affinity-depleted plasma. Thus, ASP at 40% saturation is a
      reliable depletion method that may help in proteomic analysis of blood plasma.
      Finally, ASP-depletion seems to be complementary to hydrophobic interaction
      chromatography (HIC)-depletion, and therefore an ASP-step followed by a HIC-step
      could probably deplete the most highly abundant plasma proteins, thus improving
      the detection of low abundance proteins by 2D-PAGE.

PMID- 21963275
TI  - In vitro metabolic stability and metabolite profiling of TJ0711 hydrochloride, a
      newly developed vasodilatory beta-blocker, using a liquid chromatography-tandem
      mass spectrometry method.
AB  - In this paper, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method
      was developed and validated for the simultaneous analysis of metabolic stability
      and metabolite profiling of 1-[4-(2-methoxyethyl) phenoxy]-3-[[2-(2
      methoxyphenoxy) ethyl]amino]-2-propanol hydrochloride (TJ0711 HCl), a new
      vasodilatory beta-blocker. Multiple reaction monitoring (MRM) was used as a
      survey scan to quantify the parent compound and to trigger the acquisition of
      enhanced product ions (EPI) for the identification of formed metabolites. In
      addition, comparison between MRM-only and MRM-information dependent acquisition
      EPI (MRM-IDA-EPI) methods was conducted to determine analytical variables,
      including linearity, limit of detection (LOD), lower limit of quantification
      (LLOQ), as well as intra-day and inter-day accuracy and precision. Results
      demonstrated that MRM-IDA-EPI quantitative analysis was not affected by the
      addition of EPI scans to obtain qualitative information during the same
      chromatographic run, compared to MRM-only method. Thereafter, metabolic stability
      and metabolite identification of TJ0711 HCl were investigated using human liver
      microsomes (HLM) by the MRM-IDA-EPI method. The in vitro metabolic stability
      parameters were calculated and t(1/2), microsomal intrinsic clearance (CL(int)),
      as well as hepatic CL, were 13.0 min, 106.5 MUL/min/mg microsomal protein, and
      1082.2 mL/min, respectively. The major formed metabolites were also
      simultaneously monitored and the metabolite profiling data demonstrated that this
      MRM-IDA-EPI method was capable of targeting a large number of metabolites, in
      which demethylation and hydroxylation were the principle metabolism pathways
      during the in vitro incubation with HLM.

PMID- 21963276
TI  - Simultaneous determination of asperosaponin VI and its active metabolite
      hederagenin in rat plasma by liquid chromatography-tandem mass spectrometry with
      positive/negative ion-switching electrospray ionization and its application in
      pharmacokinetic study.
AB  - A new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method operated
      in the positive/negative electrospray ionization (ESI) switching mode has been
      developed and validated for the simultaneous determination of asperosaponin VI
      and its active metabolite hederagenin in rat plasma. After addition of internal
      standards diazepam (for asperosaponin VI) and glycyrrhetic acid (for
      hederagenin), the plasma sample was deproteinized with acetonitrile, and
      separated on a reversed phase C18 column with a mobile phase of methanol (solvent
      A)-0.05% glacial acetic acid containing 10 mM ammonium acetate and 30 MUM sodium
      acetate (solvent B) using gradient elution. The detection of target compounds was
      done in multiple reaction monitoring (MRM) mode using a tandem mass spectrometry
      equipped with positive/negative ion-switching ESI source. At the first segment,
      the MRM detection was operated in the positive ESI mode using the transitions of
      m/z 951.5 ([M+Na](+))->347.1 for asperosaponin VI and m/z 285.1 ([M+H](+))->193.1
      for diazepam for 4 min, then switched to the negative ESI mode using the
      transitions of m/z 471.3 ([M-H](-))->471.3 for hederagenin and m/z 469.4 ([M-H](
      ))->425.4 for glycyrrhetic acid, respectively. The sodiated molecular ion
      [M+Na](+) at m/z 951.5 was selected as the precursor ion for asperosaponin VI,
      since it provided better sensitivity compared to the deprotonated and protonated
      molecular ions. Sodium acetate was added to the mobile phase to make sure that
      abundant amount of the sodiated molecular ion of asperosaponin VI could be
      produced, and more stable and intensive mass response of the product ion could be
      obtained. For the detection of hederagenin, since all of the mass responses of
      the fragment ions were very weak, the deprotonated molecular ion [M-H](-)m/z
      471.3 was employed as both the precursor ion and the product ion. But the
      collision energy was still used for the MRM, in order to eliminate the influences
      induced by the interference substances from the rat plasma. The validated method
      was successfully applied to study the pharmacokinetics of asperosaponin VI and
      its active metabolite hederagenin in rat plasma after oral administration of
      asperosaponin VI at a dose of 90 mg/kg.

PMID- 21963277
TI  - Bioanalysis in clinical development of tasquinimod using liquid
      chromatography/tandem mass spectrometry.
AB  - Tasquinimod (ABR-215050) is an oral drug in clinical development for treatment of
      patients with castrate resistant prostate cancer. This paper describes a method
      for the determination of tasquinimod in human plasma. The method is based on
      liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS) using
      stable isotope labeled tasquinimod as internal standard (IS). The plasma samples
      were processed by protein precipitation using acidic acetonitrile containing the
      IS. The precipitated samples were centrifuged and the supernatant was injected
      directly into the LC-MS/MS system. Chromatographic separation was performed on a
      reversed phase column using fast gradient elution, with a total run cycle time of
      4 min. The method was validated with respect to accuracy, precision, dynamic
      range, lower limit of quantification, selectivity and robustness. Furthermore,
      the stability of tasquinimod in spiked plasma, in processed extracts and in
      incurred samples was thoroughly studied. The method was validated in the range of
      1.0-2400 nmol/L, defining the lower and upper limits of quantification. The
      repeatability, reproducibility and overall bias were 1.5-7.1%, 3.5-7.4%, and 1.3
      4.7%, respectively, in the range of 1-2000 nmol/L. Excellent selectivity was
      demonstrated in the validation, as well as in study samples from both healthy
      volunteers and cancer patients. Robustness was demonstrated by the calculated
      carry-over as low as 0.06%, and by an incurred sample reproducibility (ISR)
      experiment where 97% of the reanalyzed samples fulfilled the acceptance criteria
      of 20% deviation from initial analysis result. Also, tasquinimod was found to be
      stable in all investigated matrices, including in incurred samples. In an
      incurred sample stability (ISS) investigation, tasquinimod was demonstrated to be
      stable for 24 months, and 97% of the reanalyzed samples were within 20% from the
      initial analysis result. In conclusion, the method was demonstrated to be
      accurate, precise, robust and reliable for the determination of tasquinimod. The
      method was successfully used in several clinical studies for the support of
      pharmacokinetic and pharmacodynamic evaluations.

PMID- 21963278
TI  - Developing clinical quality indicators for a Bi-National Burn Registry.
AB  - BACKGROUND: Clinical quality indicators are routinely used to benchmark and drive
      improvements in healthcare. There is a dearth of standardised clinical quality
      indicators established for management of burns that allow quality of care to be
      monitored and benchmarked across Australia and New Zealand. METHOD: Using
      published quality indicator development processes and clinician experience, the
      Bi-National Burn Registry (Bi-NBR) working party developed quality indicators for
      burn care to be included as routine data items in the Bi-NBR. RESULTS: Twenty
      indicators covering structure, process and outcome measures were identified.
      Preliminary testing resulted in further revision to the quality indicators to
      increase validity, reliability and improve data quality. The quality indicators
      are routinely collected in the Bi-NBR and reported quarterly. CONCLUSION: This is
      the first published account of the development and testing of standardised Bi
      National clinical quality indicators for burns. The Bi-NBR quality indicators
      project remains a work in progress and it is hoped that further refinement of the
      indicators, in conjunction with international collaborators will assist in
      driving improvements in burn care.

PMID- 21963279
TI  - An APETALA1-like gene of soybean regulates flowering time and specifies floral
      organs.
AB  - MADS-box proteins are key transcription factors involved in plant reproductive
      development. APETALA1 (AP1) in Arabidopsis is a MIKC-type MADS-box gene and plays
      important roles in flower development. In this research, we isolated and
      characterized GmAP1, which encoded an AP1-like protein in soybean. GmAP1
      contained eight exons and seven introns and was specifically expressed in the
      flower, especially in the sepal and petal. GmAP1 was a nucleus-localized
      transcription factor and displayed transactivation activity. It caused early
      flowering and alteration of floral organs when ectopically expressed in tobacco.
      To our knowledge, this is the first report characterizing an AP1-like gene from
      soybean.

PMID- 21963280
TI  - Circulating Glial-derived neurotrophic factor is reduced in late-life depression.
AB  - BACKGROUND: The Glial cell-line derived neurotrophic factor (GDNF) is part of the
      TGF-beta superfamily and is abundantly expressed in the central nervous system.
      Changes in GDNF homeostasis have been reported in affective disorders. AIM: To
      assess serum GDNF concentration in elderly subjects with late-life depression,
      before antidepressant treatment, as compared to healthy elderly controls.
      METHODS: Thirty-four elderly subjects with major depression and 37 age and gender
      matched healthy elderly controls were included in this study. Diagnosis of major
      depression was ascertained by the SCID interview for DSM-IV and the severity of
      depressive symptoms was assessed by the Hamilton Depression Rating Scale (HDRS
      21). Serum GDNF concentration were determined by sandwich ELISA. RESULTS:
      Patients with major depression showed a significant reduction in GDNF levels as
      compared to healthy elderly controls (p < 0.001). Also, GDNF level was negatively
      correlated with HDRS-21 scores (r = -0.343, p = 0.003). DISCUSSION: Our data
      provide evidence that GDNF may be a state marker of depressive episode in older
      adults. Changes in the homeostatic control of GDNF production may be a target to
      development of new antidepressant strategies.

PMID- 21963281
TI  - Local delivery of siRNA using a biodegradable polymer application to enhance BMP
      induced bone formation.
AB  - Small interfering RNA (siRNA) is useful tool for specific and efficient knockdown
      of disease-related genes. However, in vivo applications of siRNA are limited due
      to difficulty in its efficient delivery to target cells. In this study, we
      investigated the efficacy of a biodegradable hydrogel, poly-d,l-lactic acid-p
      dioxanone-polyethylene glycol block co-polymer (PLA-DX-PEG), as a siRNA carrier.
      PLA-DX-PEG pellets with or without fluorescein-labeled dsRNA were implanted into
      mouse dosal muscle pouches. The cellular uptake of dsRNA surround the polymer was
      confirmed by fluorescent microscopy. The fluorescence intensity was dose
      dependent of the dsRNA, and exhibited a time-dependent decrease. To investigate
      its biological efficiency, noggin (antagonoist to BMPs) gene-silencing with siRNA
      (siRNA/Noggin) was examined by the amount of suppression of BMP-2-induced noggin
      expression and the level of performance of BMP, indicated by ectopic bone
      formation. Noggin gene expression induced by BMP-2 was suppressed by addition of
      siRNA/Noggin to the implant, and the ectopic bone formation induced by implants
      with both BMP-2 and siRNA/Noggin was significantly greater than those induced by
      implants with BMP-2 alone. These results indicate the efficacy of local delivery
      of siRNAs by PLA-DX-PEG polymer, which intensified bone-inducing effects of BMP
      and promoted new bone formation by suppressing gene expression of Noggin.

PMID- 21963282
TI  - Oh the irony: Iron as a cancer cause or cure?
AB  - Iron-oxide nanoparticles facilitate cancer diagnosis through enhanced contrast,
      selectively enhance tumor cell death with magnetic hyperthermia, and improve drug
      delivery with magnetic drug targeting. One application that remains largely
      unexplored is using the iron-oxide nanoparticles themselves to selectively
      inhibit tumor growth. In this leading opinion paper, we propose that high doses
      of iron-oxide nanoparticles can be used as a treatment for cancer by generating
      an oxidative assault against cancer. This proposal may be met with resistance
      considering the controversy surrounding iron in the field of cancer. Iron
      generates reactive oxygen species through the Fenton reaction, which may both
      cause - or cure cancer. Additionally, high demand for iron by cancer cells leads
      to contradictory therapeutic approaches: iron deprivation or overdose are both
      potential cancer therapies.

PMID- 21963283
TI  - Silica-shell cross-linked micelles encapsulating fluorescent conjugated polymers
      for targeted cellular imaging.
AB  - A bioinspired silification approach was successfully used to encapsulate
      fluorescent conjugated polymers inside silica-shell cross-linked polymeric
      micelles (CP-SSCL) in the highly benign synthesis environment of room temperature
      and near-neutral aqueous environment. Four different conjugated polymers were
      employed to demonstrate the versatility of the bioinspired silification,
      resulting in the formation of CP-SSCL with different emission wavelengths across
      the visible spectrum. The CP-SSCL are characterized by a large absorption
      coefficient and high quantum yield, indicating that they exhibit the required
      high fluorescence brightness for cellular imaging application. In addition, the
      CP-SSCL also exhibit a high colloidal stability and low cytotoxicity. The in
      vitro studies of using MDA-MB-231 breast cancer cells show that the CP-SSCL are
      successfully uptaken by the cancer cells and located at the cytoplasm of the
      cells. Furthermore, by conjugating folic acid on their surfaces, the uptake of CP
      SSCL by MDA-MB-231 cells was enhanced significantly, suggesting their great
      potential for targeted imaging and early detection of cancer cells.

PMID- 21963284
TI  - Image guided, adaptive, accelerated, high dose brachytherapy as model for
      advanced small volume radiotherapy.
AB  - Brachytherapy has consistently provided a very conformal radiation therapy
      modality. Over the last two decades this has been associated with significant
      improvements in imaging for brachytherapy applications (prostate, gynecology),
      resulting in many positive advances in treatment planning, application techniques
      and clinical outcome. This is emphasized by the increased use of brachytherapy in
      Europe with gynecology as continuous basis and prostate and breast as more
      recently growing fields. Image guidance enables exact knowledge of the applicator
      together with improved visualization of tumor and target volumes as well as of
      organs at risk providing the basis for very individualized 3D and 4D treatment
      planning. In this commentary the most important recent developments in prostate,
      gynecological and breast brachytherapy are reviewed, with a focus on European
      recent and current research aiming at the definition of areas for important
      future research. Moreover the positive impact of GEC-ESTRO recommendations and
      the highlights of brachytherapy physics are discussed what altogether presents a
      full overview of modern image guided brachytherapy. An overview is finally
      provided on past and current international brachytherapy publications focusing on
      "Radiotherapy and Oncology". These data show tremendous increase in almost all
      research areas over the last three decades strongly influenced recently by
      translational research in regard to imaging and technology. In order to provide
      high level clinical evidence for future brachytherapy practice the strong need
      for comprehensive prospective clinical research addressing brachytherapy issues
      is high-lighted.

PMID- 21963285
TI  - Identifying afterloading PDR and HDR brachytherapy errors using real-time fiber
      coupled Al(2)O(3):C dosimetry and a novel statistical error decision criterion.
AB  - BACKGROUND AND PURPOSE: The feasibility of a real-time in vivo dosimeter to
      detect errors has previously been demonstrated. The purpose of this study was to:
      (1) quantify the sensitivity of the dosimeter to detect imposed treatment errors
      under well controlled and clinically relevant experimental conditions, and (2)
      test a new statistical error decision concept based on full uncertainty analysis.
      MATERIALS AND METHODS: Phantom studies of two gynecological cancer PDR and one
      prostate cancer HDR patient treatment plans were performed using tandem ring
      applicators or interstitial needles. Imposed treatment errors, including
      interchanged pairs of afterloader guide tubes and 2-20mm source displacements,
      were monitored using a real-time fiber-coupled carbon doped aluminum oxide
      (Al(2)O(3):C) crystal dosimeter that was positioned in the reconstructed tumor
      region. The error detection capacity was evaluated at three dose levels: dwell
      position, source channel, and fraction. The error criterion incorporated the
      correlated source position uncertainties and other sources of uncertainty, and it
      was applied both for the specific phantom patient plans and for a general case
      (source-detector distance 5-90 mm and position uncertainty 1-4mm). RESULTS: Out
      of 20 interchanged guide tube errors, time-resolved analysis identified 17 while
      fraction level analysis identified two. Channel and fraction level comparisons
      could leave 10mm dosimeter displacement errors unidentified. Dwell position dose
      rate comparisons correctly identified displacements >= 5mm. CONCLUSION: This
      phantom study demonstrates that Al(2)O(3):C real-time dosimetry can identify
      applicator displacements >= 5mm and interchanged guide tube errors during PDR and
      HDR brachytherapy. The study demonstrates the shortcoming of a constant error
      criterion and the advantage of a statistical error criterion.

PMID- 21963286
TI  - Functional avoidance of lung in plan optimization with an aperture-based inverse
      planning system.
AB  - PURPOSE: To implement SPECT-based optimization in an anatomy-based aperture
      inverse planning system for the functional avoidance of lung in thoracic
      irradiation. MATERIAL AND METHODS: SPECT information has been introduced as a
      voxel-by-voxel modulation of lung importance factors proportionally to the local
      perfusion count. Fifteen cases of lung cancer have been retrospectively analyzed
      by generating angle-optimized non-coplanar plans, comparing a purely anatomical
      approach and our functional approach. Planning target volume coverage and lung
      sparing have been compared. Statistical significance was assessed by a Wilcoxon
      matched pairs test. RESULTS: For similar target coverage, perfusion-weighted
      volume receiving 10 Gy was reduced by a median of 2.2% (p=0.022) and mean
      perfusion-weighted lung dose, by a median of 0.9 Gy (p=0.001). A separate
      analysis of patients with localized or non-uniform hypoperfusion could not show
      which would benefit more from SPECT-based treatment planning. Redirection of dose
      sometimes created overdosage regions in the target volume. Plans consisted of a
      similar number of segments and monitor units. CONCLUSIONS: Angle optimization and
      SPECT-based modulation of importance factors allowed for functional avoidance of
      the lung while preserving target coverage. The technique could be also applied to
      implement PET-based modulation inside the target volume, leading to a safer dose
      escalation.

PMID- 21963287
TI  - 4D-CBCT reconstruction using MV portal imaging during volumetric modulated arc
      therapy.
AB  - BACKGROUND: Recording target motion during treatment is important for verifying
      the irradiated region. Recently, cone-beam computed tomography (CBCT)
      reconstruction from portal images acquired during volumetric modulated arc
      therapy (VMAT), known as VMAT-CBCT, has been investigated. In this study, we
      developed a four-dimensional (4D) version of the VMAT-CBCT. MATERIALS AND
      METHODS: The MV portal images were sequentially acquired from an electronic
      portal imaging device. The flex, background, monitor unit, field size, and multi
      leaf collimator masking corrections were considered during image reconstruction.
      A 4D VMAT-CBCT requires a respiratory signal during image acquisition. An image
      based phase recognition (IBPR) method was performed using normalised cross
      correlation to extract a respiratory signal from the series of portal images.
      RESULTS: Our original IBPR method enabled us to reconstruct 4D VMAT-CBCT with no
      external devices. We confirmed that 4D VMAT-CBCT was feasible for two patients
      and in good agreement with in-treatment 4D kV-CBCT. CONCLUSION: The visibility of
      the anatomy in 4D VMAT-CBCT reconstruction for lung cancer patients has the
      potential of using 4D VMAT-CBCT as a tool for verifying relative positions of
      tumour for each respiratory phase.

PMID- 21963288
TI  - Clinical introduction of a linac head-mounted 2D detector array based quality
      assurance system in head and neck IMRT.
AB  - BACKGROUND AND PURPOSE: IMRT QA is commonly performed in a phantom geometry but
      the clinical interpretation of the results in a 2D phantom plane is difficult.
      The main objective of our work is to move from film measurement based QA to 3D
      dose reconstruction in a patient CT scan. In principle, this could be achieved
      using a dose reconstruction method from 2D detector array measurements as
      available in the COMPASS system (IBA Dosimetry). The first step in the clinical
      introduction of this system instead of the currently used film QA procedures is
      to test the reliability of the dose reconstruction. In this paper we investigated
      the validation of the method in a homogeneous phantom with the film QA procedure
      as a reference. We tested whether COMPASS QA results correctly identified
      treatment plans that did or did not fulfil QA requirements in head and neck (H&N)
      IMRT. MATERIALS AND METHODS: A total number of 24 treatments were selected from
      an existing database with more than 100 film based H&N IMRT QA results. The QA
      results were classified as either good, just acceptable or clinically rejected
      (mean gamma index <0.4, 0.4-0.5 or >0.5, respectively with 3%/3mm criteria). Film
      QA was repeated and compared to COMPASS QA with a MatriXX detector measurement
      performed on the same day. RESULTS: Good agreement was found between COMPASS
      reconstructed dose and film measured dose in a phantom (mean gamma 0.83+/-0.09,
      1SD with 1%/1mm criteria, 0.33+/-0.04 with 3%/3mm criteria). COMPASS QA results
      correlated well with film QA, identifying the same patients with less good QA
      results. Repeated measurements with film and COMPASS showed changes in delivery
      after a modified MLC calibration, also visible in a standard MLC check in
      COMPASS. The time required for QA reduced by half by using COMPASS instead of
      film. CONCLUSIONS: Agreement of COMPASS QA results with film based QA supports
      its clinical introduction for a phantom geometry. A standard MLC calibration
      check is sensitive to <1mm changes that could be significant in H&N IMRT. These
      findings offer opportunities to further investigate the method based on a 2D
      detector array to 3D dose reconstruction in a patient anatomy.

PMID- 21963289
TI  - Application of a spacer gel to optimize three-dimensional conformal and intensity
      modulated radiotherapy for prostate cancer.
AB  - BACKGROUND AND PURPOSE: The aim was to evaluate the impact of a spacer gel on the
      dose distribution, applying three-dimensional conformal (3D CRT) and intensity
      modulated radiotherapy (IMRT) planning techniques. MATERIAL AND METHODS: The
      injection of a spacer gel (10 ml SpaceOARTM) was performed between the prostate
      and rectum under transrectal ultrasound guidance in 18 patients with prostate
      cancer. 3D CRT and IMRT treatment plans were compared based on CT before and
      after injection (78 Gy prescription dose). RESULTS: In contrast to the PTV and
      bladder, significant advantages (p<0.01) resulted in respect of all analysed
      rectal dose values comparing pre spacer with post spacer plans for both
      techniques. Rectal NTCP (normal tissue complication probability) reached the
      lowest percentage after spacer injection irrespective of the technique, with a
      mean reduction of >50% for both IMRT and 3D CRT. Significantly (p<0.01) higher
      D(mean), and V(78) for the PTV were reached with IMRT vs. 3D CRT plans, with a
      smaller rectum V(76) but larger rectum V(50). CONCLUSIONS: The injection of a
      spacer gel between the prostate and anterior rectal wall is associated with
      considerably lower doses to the rectum and consequentially lower NTCP values
      irrespective of the radiotherapy technique.

PMID- 21963290
TI  - Determination of the correction factors for different ionization chambers used
      for the calibration of the helical tomotherapy static beam.
AB  - BACKGROUND AND PURPOSE: To determine the machine-specific correction factors for
      three commercial ionization chambers (Exradin A1SL, PTW Semiflex and PTW
      PinPoint) to be applied in the dose calibration of a helical tomotherapy (HT)
      unit. MATERIALS AND METHODS: Machine-specific reference (msr) conditions for HT
      unit involved a 10 * 5 cm(2) (IEC x*y) radiation field at 85 cm SSD with the
      ionization chamber (IC) positioned at 10 cm depth in Virtual Water. Each msr
      correction factor was determined using the formalism proposed by the AAPM Task
      Group 148 (i.e. k(Q[HT)(TG-51])) and was compared to direct calibration of the
      ICs against radiochromic films, calibrated in absolute dose at our institute,
      following the formalism proposed by the IAEA-AAPM joint committee (i.e. [Formula:
      see text] ). RESULTS: TPR(20,10) values under HT msr conditions were 0.608, 0.608
      and 0.615 corresponding to %dd(10)(x[HT)(Ref]) of 0.606, 0.606 and 0.613 for
      A1SL, Semiflex and PinPoint ICs, respectively. Based on these findings,
      k(Q[HT)(TG-51]) determination resulted 0.998+/-0.001, 0.998+/-0.001 and 0.991+/
      0.002 for A1SL, Semiflex and PinPoint ICs, respectively. The [Formula: see text]
      correction factors obtained through direct calibration were 1.000+/-0.010,
      1.004+/-0.007 and 0.998+/-0.006 for A1SL, Semiflex and PinPoint ICs,
      respectively. CONCLUSIONS: Direct calibration of ICs versus radiochromic films
      provided correction factors equivalent to those obtained following the TG-148
      formalism. This study showed that ICs calibrated for conventional linear
      accelerators can be used for the calibration of the static beam delivered by a HT
      unit taking into account the particular reference conditions.

PMID- 21963291
TI  - Efficacy of two vaccine formulations against contagious bovine pleuropneumonia
      (CBPP) in Kenyan indigenous cattle.
AB  - A live, attenuated vaccine is currently the only viable option to control of CBPP
      in Africa. It has been suggested that simple modifications to current vaccines
      and protocols might improve efficacy in the field. In this report we compared the
      current vaccine formulation with a buffered preparation that maintains Mycoplasma
      viability at ambient temperature for a longer time. Groups of animals were
      vaccinated with the two formulations and compared with non vaccinated groups.
      Half of the animals in each group were challenged 3 months post vaccination, the
      other half after 16 months. Protection levels were measured using the pathology
      index, calculated from post mortem scores of lesions from animals killed during
      the course of clinical disease. In the challenge at 3 months post vaccination,
      the protection levels were 52% and 77% for the modified and current vaccine
      preparations, respectively. At 16 months post vaccination, the protection levels
      were 56% and 62% for the modified and current vaccine preparations, respectively.
      These findings indicate that there are no differences in protection levels
      between the two vaccines. Because of its longer half life after reconstitution,
      the modified vaccine might be preferred in field situations where the
      reconstituted vaccine is likely not to be administered immediately.

PMID- 21963292
TI  - Detection and measurement of carbohydrate deficient transferrin in serum using
      immuno-capture mass spectrometry: diagnostic applications for annual ryegrass
      toxicity and corynetoxin exposure.
AB  - The neurological livestock disease annual ryegrass toxicity (ARGT) is caused by
      the ingestion of the naturally occurring glycolipid toxins - the corynetoxins.
      Corynetoxins also threaten human health as potential contaminants of the food
      supply. Presently, there are no routine diagnostic tests for corynetoxins
      exposure in humans or livestock. Chronic ingestion of corynetoxins has been
      modeled in rats exposed to dietary tunicamycins for 12 months and carbohydrate
      deficient transferrin (CDT) has been previously identified as a candidate disease
      biomarker. Here, the technique of immuno-capture mass spectrometry (icMS) was
      used to evaluate serum levels of CDT, discriminating between control and
      tunicamycins-exposed rats with 85% accuracy. The icMS approach is based on the
      combination of specific transferrin enrichment with functionalized magnetic beads
      and automated matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF MS). With no other clinically-relevant diagnostic tests
      available icMS could be readily adapted for high-throughput clinical assessment
      of corynetoxins-exposure in humans or livestock.

PMID- 21963293
TI  - Milk-flow, ultrasonographic, theloscopic, and histopathological characteristics
      of the teat in cows with toxic mastitis.
AB  - The milk-flow, imaging, and histopathological characteristics of the teat in five
      cows with toxic mastitis were investigated. Teats were grouped into type I
      (without gross and histopathological abnormality), type II (no abnormal gross
      findings, but with histopathological abnormality), and type III (with gross and
      histopathological abnormality). Normal teats from six cows served as controls.
      Type II and III teats had lower milk-flow, compared with the controls.
      Ultrasonography revealed no abnormal findings, except for irregular mucosal
      surface in type II teats and absence of hyperechoic line along the teat canal in
      type III teats. The theloscopic findings varied from normal to mucosal
      abnormalities in type II and III teats. Histopathology demonstrated epithelial
      changes, congestion, hemorrhage, edema, cellular infiltration, and elastic fiber
      degradation in type II and III teats, with the type III teats showing severe
      changes. Toxic mastitis was characterized by impaired milk-flow and various
      degrees of imaging and histopathological abnormality.

PMID- 21963294
TI  - Reversible jump MCMC methods for fully automatic motion analysis in tagged MRI.
AB  - Tagged magnetic resonance imaging (tMRI) is a well-known noninvasive method for
      studying regional heart dynamics. It offers great potential for quantitative
      analysis of a variety of kine(ma)tic parameters, but its clinical use has so far
      been limited, in part due to the lack of robustness and accuracy of existing tag
      tracking algorithms in dealing with low (and intrinsically time-varying) image
      quality. In this paper, we evaluate the performance of four frequently used
      concepts found in the literature (optical flow, harmonic phase (HARP) magnetic
      resonance imaging, active contour fitting, and non-rigid image registration) for
      cardiac motion analysis in 2D tMRI image sequences, using both synthetic image
      data (with ground truth) and real data from preclinical (small animal) and
      clinical (human) studies. In addition we propose a new probabilistic method for
      tag tracking that serves as a complementary step to existing methods. The new
      method is based on a Bayesian estimation framework, implemented by means of
      reversible jump Markov chain Monte Carlo (MCMC) methods, and combines information
      about the heart dynamics, the imaging process, and tag appearance. The
      experimental results demonstrate that the new method improves the performance of
      even the best of the four previous methods. Yielding higher consistency,
      accuracy, and intrinsic tag reliability assessment, the proposed method allows
      for improved analysis of cardiac motion.

PMID- 21963295
TI  - Generalized likelihood ratio tests for change detection in diffusion tensor
      images: application to multiple sclerosis.
AB  - The automatic analysis of subtle changes between MRI scans is an important tool
      for monitoring disease evolution. Several methods have been proposed to detect
      changes in serial conventional MRI but few works have considered Diffusion Tensor
      Imaging (DTI), which is a promising modality for monitoring neurodegenerative
      disease and particularly Multiple Sclerosis (MS). In this paper, we introduce a
      comprehensive framework for detecting changes between two DTI acquisitions by
      considering different levels of representation of diffusion imaging, namely the
      Apparent Diffusion Coefficient (ADC) images, the diffusion tensor fields, and
      scalar images characterizing diffusion properties such as the fractional
      anisotropy and the mean diffusivity. The proposed statistical method for change
      detection is based on the Generalized Likelihood Ratio Test (GLRT) that has been
      derived for the different diffusion imaging representations, based on the core
      assumption of a Gaussian diffusion model and of an additive Gaussian noise on the
      ADCs. Results on synthetic and real images demonstrate the ability of the
      different tests to bring useful and complementary information in the context of
      the follow-up of MS patients.

PMID- 21963296
TI  - Towards robust and effective shape modeling: sparse shape composition.
AB  - Organ shape plays an important role in various clinical practices, e.g.,
      diagnosis, surgical planning and treatment evaluation. It is usually derived from
      low level appearance cues in medical images. However, due to diseases and imaging
      artifacts, low level appearance cues might be weak or misleading. In this
      situation, shape priors become critical to infer and refine the shape derived by
      image appearances. Effective modeling of shape priors is challenging because: (1)
      shape variation is complex and cannot always be modeled by a parametric
      probability distribution; (2) a shape instance derived from image appearance cues
      (input shape) may have gross errors; and (3) local details of the input shape are
      difficult to preserve if they are not statistically significant in the training
      data. In this paper we propose a novel Sparse Shape Composition model (SSC) to
      deal with these three challenges in a unified framework. In our method, a sparse
      set of shapes in the shape repository is selected and composed together to
      infer/refine an input shape. The a priori information is thus implicitly
      incorporated on-the-fly. Our model leverages two sparsity observations of the
      input shape instance: (1) the input shape can be approximately represented by a
      sparse linear combination of shapes in the shape repository; (2) parts of the
      input shape may contain gross errors but such errors are sparse. Our model is
      formulated as a sparse learning problem. Using L1 norm relaxation, it can be
      solved by an efficient expectation-maximization (EM) type of framework. Our
      method is extensively validated on two medical applications, 2D lung localization
      in X-ray images and 3D liver segmentation in low-dose CT scans. Compared to state
      of-the-art methods, our model exhibits better performance in both studies.

PMID- 21963297
TI  - Mediastinitis and blood transfusion in cardiac surgery: a systematic review.
AB  - BACKGROUND: Mediastinitis, a serious complication after cardiac surgery,
      increases morbidity, mortality, and cost of care. Accumulating evidence
      implicates blood transfusions in the development of mediastinitis. OBJECTIVES: We
      conducted a systematic review to evaluate the association between allogeneic
      blood transfusion and mediastinitis in adult cardiac surgery patients. RESULTS:
      After a search of Medline, PubMed, Cochrane Library, the Cumulative Index to
      Nursing and Allied Health Literature, and the Institute for Scientific
      Information's Web of Knowledge (1990-2010) for relevant studies, 7 (3 prospective
      cohort and 4 retrospective reviews) met our inclusion/exclusion criteria. Between
      20% and 80.2% of patients received blood transfusions, with an incidence of
      mediastinitis ranging from 0.1% to 2.3%. Five studies demonstrated an independent
      association between red blood cell transfusion and mediastinitis. Two studies
      identified a dose-response relationship. CONCLUSION: The findings of this
      systematic review suggest that allogeneic red blood cell transfusions are
      associated with an increased risk of mediastinitis in patients undergoing cardiac
      surgery. Individual risks and benefits should be assessed in each patient before
      a red blood cell transfusion.

PMID- 21963298
TI  - Post discharge follow up phone call.

PMID- 21963299
TI  - mTOR signaling in disease.
AB  - The target of rapamycin (TOR) is a highly conserved serine/threonine kinase and a
      central controller of cell growth, metabolism and aging. Mammalian TOR (mTOR) is
      activated in response to nutrients, growth factors and cellular energy.
      Dysregulated mTOR signaling has been implicated in major disease. Here we review
      recent findings on the role of mTOR in cancer, metabolic disorders, neurological
      diseases, and inflammation.

PMID- 21963300
TI  - Origins and consequences of transcriptional discontinuity.
AB  - In both prokaryotes and eukaryotes, transcription has been described as being
      temporally discontinuous, most genes being active mainly during short activity
      windows interspersed by silent periods. In mammalian cells, recent studies
      performed at the single cell level have revealed that transcriptional kinetics
      are highly gene-specific and constrained by the presence of refractory periods of
      inactivity before a gene can be turned on again. While the underlying mechanisms
      generating gene-specific kinetic characteristics remain unclear, various
      biological consequences of transcriptional discontinuity have been unravelled
      during the past few years. Here we review recent advances on understanding
      transcriptional kinetics of individual genes at the single cell level and discuss
      its possible origins and consequences.

PMID- 21963301
TI  - Robust selection of sensory organ precursors by the Notch-Delta pathway.
AB  - The patterning of multicellular organisms is robust to environmental, genetic, or
      stochastic fluctuations. Mathematical modeling is instrumental in identifying
      mechanisms supporting this robustness. The principle of lateral inhibition,
      whereby a differentiating cell inhibits its neighbors from adopting the same
      fate, is frequently used for selecting a single cell out of a cluster of
      equipotent cells. For example, Sensory Organ Precursors (SOP) in the fruit-fly
      Drosophila implement lateral inhibition by activating the Notch-Delta pathway. We
      discuss parameters affecting the rate of errors in this process, and the
      mechanism (inhibitory cis interaction between Notch and Delta) predicted to
      reduce this error.

PMID- 21963302
TI  - The detection of a transgenic soybean biochip using gold label silver stain
      technology.
AB  - A method for the rapid detection of transgenic soybean crops based on a
      combination of gene chip and "gold label silver stain" (GLSS) technologies has
      been established. To ensure the specificity of this method, the CaMV35S promoter
      and Nos terminator were selected as probes because they are both exogenous genes
      that are specific to transgenic soybean plants. The addition of biotin-modified
      dUTPs to a polymerase chain reaction (PCR) system can produce amplified nucleic
      acid segments containing biotin. These labeled PCR products then hybridize with
      specific probes on the chip and are subsequently bound by streptavidin-modified
      gold nanoparticles (GNPs). Due to the catalytic nature of the GNPs, silver
      staining can be used to visualize the hybridized probes, which appear as signals
      in varying shades of gray. The intensity value of the gray signals can be
      obtained using a general scanner. Silver staining for 10 min was determined to
      produce the optimal signal-to-noise ratio. In addition, this method was shown to
      be highly specific and had a detection sensitivity of 288.57 pg/MUL.

PMID- 21963303
TI  - Cytotoxic and antivascular 1-methyl-4-(3-fluoro-4-methoxyphenyl)-5-(halophenyl)
      imidazoles.
AB  - A series of 1-methyl-4,5-diphenylimidazoles 6 with various patterns of m-halogen
      substitution at the 5-phenyl ring were tested for cytotoxicity in cancer and
      nonmalignant cell lines and for their capacity to prevent tube formation in HUVEC
      cultures. Unlike the monofluoro and difluoro derivatives 6a and 6e, the monobromo
      and diiodo analogs 6c and 6h were strongly cytotoxic and inhibited the
      polymerization of tubulin and the tube formation by HUVEC. The dibromo derivative
      6g displayed a unique selectivity for KB-3-1 cervix and PC-3 prostate cancer
      cells. It also inhibited the tube formation by HUVEC and the polymerization of
      tubulin which is indicative of its potential antiangiogenic activity in solid
      tumors.

PMID- 21963304
TI  - Stable and orally bio-available pro-drugs of CPS11.
AB  - Stable and orally bio-available pro-drugs of CPS11 were synthesized. They are
      active on human umbilical vein endothelial cell proliferation assay and tube
      formation assay. The therapeutic efficacy and safety of 4 as a single agent or
      combined with Taxol in the treatment of MX-1 human breast cancer xenograft were
      evaluated. Compound 4 as a single agent failed to produce an anti-tumor activity,
      while it significantly enhanced antitumor potency of Taxol.

PMID- 21963305
TI  - BRN-103, a novel nicotinamide derivative, inhibits VEGF-induced angiogenesis and
      proliferation in human umbilical vein endothelial cells.
AB  - Anti-angiogenesis is regarded as an effective strategy for cancer treatment, and
      vascular endothelial growth factor (VEGF) plays a key role in the regulations of
      angiogenesis and vasculogenesis. In the present study, the authors synthesized
      five novel nicotinamide derivatives which structurally mimic the receptor
      tyrosine kinase inhibitor sunitinib and evaluated their anti-angiogenic effects.
      Transwell migration assays revealed that 2-(1-benzylpiperidin-4-yl) amino-N-(3
      chlorophenyl) nicotinamide (BRN-103), among the five derivatives most potently
      inhibited VEGF-induced human umbilical vein endothelial cells (HUVECs). In
      addition, BRN-103 dose-dependently inhibited VEGF-induced migration,
      proliferation, and capillary-like tube formation of HUVECs and vessel sprouting
      from mouse aortic rings. To understand the molecular mechanisms responsible for
      these activities, the authors examined the effect of BRN-103 on VEGF signaling
      pathways in HUVECs. BRN-103 was found to suppress the VEGF-induced
      phosphorylation of VEGF receptor 2 (VEGR2) and the activations of AKT and eNOS.
      Taken together, these results suggest that BRN-103 inhibits VEGF-mediated
      angiogenesis signaling in human endothelial cells.

PMID- 21963306
TI  - Effect of calcium cation on lipid vesicle deposition on silicon dioxide surface
      under various thermal conditions.
AB  - Calcium cation (Ca(2+)) is a key element to the cell membrane functions. Its
      effects on liquid crystal vesicle deposition have already been learnt. In this
      study, it is found that Ca(2+) can also influence the gel vesicle deposition by
      controlling the vesicle rupture and fusion on SiO(2) at temperatures lower than
      the main transition temperature. Particular analyses were given to the vesicle
      SiO(2) and inter-vesicle attractions that are originated from the Ca(2+) bridging
      effect. It is concluded that the aggregate condition of vesicles should be taken
      into consideration when dealing with vesicle deposition on a solid substrate.

PMID- 21963307
TI  - Prevalence and demographic characteristics of vulvodynia in a population-based
      sample.
AB  - OBJECTIVE: The objective of the study was to determine the prevalence and
      characteristics of vulvodynia among women in southeast Michigan. STUDY DESIGN: A
      population-based study of adult women was conducted, using telephone recruitment
      and completion of a self-administered survey. Weighted estimates of vulvodynia
      prevalence and characteristics were determined. RESULTS: Over a year, 2542 women
      were recruited and 2269 (89.3%) completed the self-administered survey. The
      weighted prevalence of vulvodynia was 8.3% (95% confidence interval, 7.0-9.8) or
      approximately 101,000 women in the targeted population. Prevalence remained
      stable through age 70 years and declined thereafter. Among sexually active women,
      the prevalence was similar at all ages. Of 208 women meeting vulvodynia criteria,
      101 (48.6%) had sought treatment, and only 3 (1.4%) had been diagnosed with
      vulvodynia (unweighted values). Previous vulvodynia symptoms had resolved in 384
      women (16.9%) after a mean duration of 12.5 years. CONCLUSION: Vulvodynia is
      common, although rarely diagnosed. Prevalence remains high among sexually active
      women of any age.

PMID- 21963309
TI  - Electronic fetal heart rate monitoring and its relationship to neonatal and
      infant mortality in the United States.

PMID- 21963308
TI  - Etiology and management of postpartum hypertension-preeclampsia.
AB  - Postpartum hypertension can be related to persistence of gestational
      hypertension, preeclampsia, or preexisting chronic hypertension, or it could
      develop de novo postpartum secondary to other causes. There are limited data
      describing the etiology, differential diagnosis, and management of postpartum
      hypertension-preeclampsia. The differential diagnosis is extensive, and varies
      from benign (mild gestational or essential hypertension) to life-threatening such
      as severe preeclampsia-eclampsia, pheochromocytoma, and cerebrovascular
      accidents. Therefore, medical providers caring for postpartum women should be
      educated about continued monitoring of signs and symptoms and prompt management
      of these women in a timely fashion. Evaluation and management should be performed
      in a stepwise fashion and may require a multidisciplinary approach that considers
      predelivery risk factors, time of onset, associated signs/symptoms, and results
      of selective laboratory and imaging findings. The objective of this review is to
      increase awareness and to provide a stepwise approach toward the diagnosis and
      management of women with persistent and/or new-onset hypertension-preeclampsia
      postpartum period.

PMID- 21963310
TI  - Postpartum intrauterine device insertion and postpartum tubal sterilization in
      the United States.
AB  - OBJECTIVE: The purpose of this study was to estimate US rates of postpartum
      intrauterine device (IUD) insertion and postpartum tubal sterilization. STUDY
      DESIGN: Data from the 2001-2008 Nationwide Inpatient Sample were used to identify
      delivery hospitalizations with IUD insertion or tubal sterilization procedure
      codes. RESULTS: Estimated rates of postpartum IUD insertion and postpartum tubal
      sterilization were 0.27 and 770.67 per 10,000 deliveries, respectively. Although
      the rate of IUD insertion was similar across age groups, the rate of tubal
      sterilization increased with age. Nonetheless, 15% of tubal sterilizations
      occurred among women who were <= 24 years old. IUD insertion was more likely
      among women who delivered at teaching hospitals (odds ratio, 3.02; 95% confidence
      interval, 1.43-6.37); tubal sterilization was more likely among women without
      private insurance (odds ratio, 2.04; 95% confidence interval, 1.97-2.11).
      CONCLUSION: Among US postpartum women, IUD insertion occurs considerably less
      frequently than tubal sterilization, even among younger women for whom
      poststerilization regret is a concern.

PMID- 21963311
TI  - Oversight of elective early term deliveries: avoiding unintended consequences.
AB  - The national movement to eliminate elective delivery at <39 weeks' gestation has
      engendered much enthusiasm and is a major step forward in the evolution of
      perinatal patient safety. Our experience with >1 million births in the past 5
      years suggests the existence of a number of potential pitfalls that should be
      considered in policy development, enforcement, and compliance monitoring.
      Attention to these details will ensure continued patient benefit from these
      policies without endangering those fetuses in whom early term delivery is
      warranted medically.

PMID- 21963312
TI  - Addressing literacy as a barrier in delivery and evaluation of cognitive
      behavioral therapy for pain management.

PMID- 21963313
TI  - A neurophysiological analysis of working memory in amyotrophic lateral sclerosis.
AB  - Frontal lobe functions, in particular working memory (WM) and verbal fluency,
      have been found to be deficient in amyotrophic lateral sclerosis (ALS). To study
      the neural correlates of WM-impairment, ALS patients and healthy age-matched
      controls were subjected to two working memory tasks following the 2-back
      paradigm, one requiring the storage of figural information, the other storage of
      spatial information. A significant proportion of ALS patients were unable to
      perform the WM-tasks. Those who could showed worse performance in the spatial
      task than the controls. Event-related brain potentials recorded during the task
      revealed a topographical change of the working memory effect in the ALS patients.
      Thus, behavioral and electrophysiological data suggest an alteration of working
      memory, in particular for spatial information, in ALS. Additionally, the patients
      also took part in two Go/Nogo tasks (spatial, figural) using the same stimulus
      material but defining targets prior to the experiment instead of a working memory
      manipulation. Here, an anteriorization of the nogo-P3 was found which has been
      established as an index of impaired inhibitory functions.

PMID- 21963314
TI  - Projections from the anteroventral part of the medial amygdaloid nucleus in the
      rat.
AB  - The medial amygdaloid nucleus (Me) integrates pheromonal and olfactory
      information with gonadal hormone cues, being implicated in social behaviors. It
      is divided cytoarchitectonically in an anterodorsal, anteroventral (MeAV),
      posterodorsal and posteroventral part, whose projections are well characterized,
      except for those of the tiny MeAV. Here, MeAV efferents were examined in the rat
      with the anterograde Phaseolus vulgaris leucoagglutinin (PHA-L) and retrograde
      Fluoro-Gold (FG) tracers and compared with those of other Me parts. The present
      PHA-L observations show that the MeAV projects profusely to itself, but its
      projections to other Me parts are modest. In conjunction with FG experiments,
      they suggest that the MeAV innervates robustly a restricted set of structures it
      shares with the anterodorsal and/or posteroventral Me. Its major targets are the
      core of the ventromedial hypothalamic nucleus (especially the dorsomedial and
      central parts), reached mainly via the stria terminalis, and the amygdalostriatal
      transition area. In addition, the MeAV innervates substantially the lateral and
      posterior basomedial amygdaloid nuclei and the intraamygdaloid bed nucleus of the
      stria terminalis. In contrast to other Me parts, it provides only modest inputs
      to the main and accessory olfactory systems, medial bed nucleus of the stria
      terminalis and reproductive hypothalamic nuclei. This anatomical framework
      suggests that the MeAV may play a role in orienting responses to chemosensory
      cues and defensive behaviors elicited by the odor of predators.

PMID- 21963315
TI  - Modulation of auditory-evoked potentials recorded in the inferior colliculus by
      GABAergic mechanisms in the basolateral and central nuclei of the amygdala in
      high- and low-anxiety rats.
AB  - The central nucleus of the inferior colliculus (CIC) is an important relay
      station for acoustic information that has an aversive connotation. gamma
      Aminobutyric acid (GABA) mechanisms exert tonic inhibitory control over the
      neural substrates of aversion in the midbrain tectum. Recent evidence obtained in
      this laboratory showed that low- (LA) and high-anxiety (HA) rats selected in the
      elevated plus maze (EPM) exhibit low and high auditory-evoked potential (AEP)
      amplitudes, respectively, recorded in the CIC when subjected to loud click
      noises. The present study investigated the eventual top-down regulation exerted
      by GABA mechanisms in the basolateral (BLA) and central (CeA) nuclei of the
      amygdala on aversive information processing at the level of the CIC. The GABA
      inhibitors bicuculline (10 ng/0.2 MUl) and semicarbazide (7 MUg/0.2 MUl) and GABA
      agonist muscimol (1 nmol/0.2 MUl) were locally infused into the CeA and BLA in
      rats subjected to an AEP recording procedure that used electrodes implanted in
      the CIC. Freezing behavior induced by these intra-amygdala injections was also
      measured. The results confirmed that the processing of aversive acoustic
      information depends on anxiety levels in LA and HA rats. Freezing behavior and
      the increased AEPs induced by intra-CeA injections of bicuculline and
      semicarbazide were more pronounced in HA than in LA animals. Intra-CeA injections
      of muscimol did not change either the basal levels of freezing or AEP amplitudes
      in LA and HA rats. However, freezing and the enhanced AEPs were of small
      magnitude following intra-BLA injections of bicuculline and semicarbazide. An
      unexpected magnitude of freezing and enhanced AEPs was observed following
      muscimol infusions into the BLA in HA rats. GABA mechanisms in the CeA appear to
      play a regulatory role in aversive states, and inactivation of the BLA with
      muscimol produced pro-aversive effects, suggesting that inactivation of the BLA
      removed the descending inhibitory control of the neural substrates of aversion in
      the CIC exerted by the BLA. Because the latter effects were observed only in HA
      rats, a dysfunctional BLA may underlie the differences between trait and state
      anxiety.

PMID- 21963316
TI  - A randomized, controlled trial to test the efficacy of an online, parent-based
      intervention for reducing the risks associated with college-student alcohol use.
AB  - Alcohol consumption among college students remains a major public health concern.
      Universal, Web-based interventions to reduce risks associated with student
      alcohol consumption have been found to be effective in changing their alcohol
      related behavior. Recent studies also indicate that parent-based interventions,
      delivered in booklet form, are effective. A parent-based intervention that is
      also Web-based may be well suited to a dispersed parent population; however, no
      such tool is currently available. The purpose of this study was to test the
      efficacy of an online parent-based intervention designed to (1) increase
      communication between parents and students about alcohol and (2) reduce risks
      associated with alcohol use to students. A total of 558 participants, comprising
      279 parent-teen dyads, were enrolled in the study. The findings suggested that
      parents who participated in the online intervention were more likely to discuss
      protective behavioral strategies, particularly those related to manner of
      drinking and stopping/limiting drinking, with their teens, as compared with
      parents in an e-newsletter control group. Moreover, students whose parents
      received the intervention were more likely to use a range of protective
      behavioral strategies, particularly those related to manner of drinking and
      stopping/limiting drinking, as compared with students whose parents did not
      receive the intervention. A universal, online, parent-based intervention to
      reduce risks associated with student alcohol consumption may be an efficient and
      effective component of a college's overall prevention strategy.

PMID- 21963317
TI  - Episodes of care: is emergency medicine ready?
AB  - Optimizing resource use, eliminating waste, aligning provider incentives,
      reducing overall costs, and coordinating the delivery of quality care while
      improving outcomes have been major themes of health care reform initiatives.
      Recent legislation contains several provisions designed to move away from the
      current fee-for-service payment mechanism toward a model that reimburses
      providers for caring for a population of patients over time while shifting more
      financial risk to providers. In this article, we review current approaches to
      episode of care development and reimbursement. We describe the challenges of
      incorporating emergency medicine into the episode of care approach and the
      uncertain influence this delivery model will have on emergency medicine care,
      including quality outcomes. We discuss the limitations of the episode of care
      payment model for emergency services and advocate retention of the current fee
      for-service payment model, as well as identify research gaps that, if addressed,
      could be used to inform future policy decisions of emergency medicine health
      policy leaders. We then describe a meaningful role for emergency medicine in an
      episode of care setting.

PMID- 21963318
TI  - Modulating effects of bodyweight unloading on the lower limb nociceptive
      withdrawal reflex during symmetrical stance.
AB  - OBJECTIVE: To investigate the effects of bodyweight unloading on the excitability
      of the nociceptive withdrawal reflex (NWR) and of its receptive fields
      organisation during quiet stance in humans. METHODS: The NWR was elicited in 14
      volunteers by electrical stimulation of the sole of the foot at mid-forefoot,
      arch, and heel points. Participants stood upright and wore a whole-body harness
      connected via a rope to a pulley. Data were recorded at 0%, 10%, 25% and 40% of
      the bodyweight unloading. The root mean square of the EMG activity was measured
      bilaterally from several lower limb muscles. Kinematics of ankle, knee, and hip
      were measured bilaterally using goniometers. RESULTS: Two-way ANOVA for repeated
      measures revealed higher reflex sizes at higher degrees of unloading in the
      tibialis anterior, soleus, and biceps femoris muscles and in the kinematics of
      the knee joint of the ipsilateral limb. No interaction between stimulation site
      and unloading was revealed. CONCLUSIONS: Unloading induced a generalised
      enhancement of NWR excitability without modifying the reflex receptive field
      organisation. SIGNIFICANCE: Our study indicates that bodyweight unloading in
      general enhances the NWR excitability and suggests that only load-related
      afferent inputs in concert with joint movements may modify the modular
      organisation of the NWR.

PMID- 21963319
TI  - Limb segment vibration modulates spinal reflex excitability and muscle mRNA
      expression after spinal cord injury.
AB  - OBJECTIVE: We investigated the effect of various doses of vertical oscillation
      (vibration) on soleus H-reflex amplitude and post-activation depression in
      individuals with and without SCI. We also explored the acute effect of short-term
      limb vibration on skeletal muscle mRNA expression of genes associated with spinal
      plasticity. METHODS: Six healthy adults and five chronic complete SCI subjects
      received vibratory stimulation of their tibia over three different gravitational
      accelerations (0.3g, 0.6g, and 1.2g) at a fixed frequency (30Hz). Soleus H
      reflexes were measured before, during, and after vibration. Two additional
      chronic complete SCI subjects had soleus muscle biopsies 3h following a single
      bout of vibration. RESULTS: H-reflex amplitude was depressed over 83% in both
      groups during vibration. This vibratory-induced inhibition lasted over 2min in
      the control group, but not in the SCI group. Post-activation depression was
      modulated during the long-lasting vibratory inhibition. A single bout of
      mechanical oscillation altered mRNA expression from selected genes associated
      with synaptic plasticity. CONCLUSIONS: Vibration of the lower leg inhibits the H
      reflex amplitude, influences post-activation depression, and alters skeletal
      muscle mRNA expression of genes associated with synaptic plasticity.
      SIGNIFICANCE: Limb segment vibration may offer a long term method to reduce
      spinal reflex excitability after SCI.

PMID- 21963320
TI  - Increased baseline temperature improves the acquisition of contact heat evoked
      potentials after spinal cord injury.
AB  - OBJECTIVE: To investigate the effect of increasing the skin surface baseline
      temperature for contact heat evoked potentials (CHEPs). METHODS: CHEPs were
      studied in healthy subjects and subjects with chronic cervical spinal cord injury
      (SCI) using a conventional 35 degrees C (condition 1) or increased 42-45 degrees
      C baseline temperature (condition 2). A third condition was used to standardize
      the contact heat stimulus duration from the different baseline temperatures.
      Changes in peak latency and N2P2 amplitude of the CHEPs and rating of perceived
      intensity were examined between conditions. RESULTS: In healthy subjects,
      increasing the baseline temperature for contact heat stimulation significantly
      increased the rating of perceived intensity (conditions 2 and 3), as well as the
      amplitude of CHEPs (condition 2 only). Following SCI, an increased baseline
      temperature facilitated perception of contact heat stimulation and evoked
      potentials could be recorded from dermatomes that were insensitive to contact
      heat from a conventional baseline temperature. CONCLUSIONS: Enhancing the
      acquisition of CHEPs can be achieved by increasing the baseline temperature. This
      effect can be attributed, in part, to shortening the stimulation duration.
      SIGNIFICANCE: After SCI, increasing the baseline temperature for CHEPs in
      dermatomes with absent or diminished sensation improved the neurophysiological
      resolution of afferent sparing.

PMID- 21963322
TI  - Anticholinergic activity of antihistamines.

PMID- 21963323
TI  - Primary adenosquamous carcinoma of the cecum.

PMID- 21963321
TI  - Dissociation of motor and sensory inhibition processes in normal aging.
AB  - OBJECTIVE: Age-related cognitive impairments have been attributed to deficits in
      inhibitory processes that mediate both motor restraint and sensory filtering.
      However, behavioral studies have failed to show an association between tasks that
      measure these distinct types of inhibition. In the present study, we hypothesized
      neural markers reflecting each type of inhibition may reveal a relationship
      across inhibitory domains in older adults. METHODS: Electroencephalography (EEG)
      and behavioral measures were used to explore whether there was an across
      participant correlation between sensory suppression and motor inhibition. Sixteen
      healthy older adult participants (65-80 years) engaged in two separate
      experimental paradigms: a selective attention, delayed-recognition task and a
      stop-signal task. RESULTS: Findings revealed no significant relationship existed
      between neural markers of sensory suppression (P1 amplitude; N170 latency) and
      markers of motor inhibition (N2 and P3 amplitude and latency) in older adults.
      CONCLUSIONS: These distinct inhibitory domains are differentially impacted in
      normal aging, as evidenced by previous behavioral work and the current neural
      findings. Thus a generalized inhibitory deficit may not be a common impairment in
      cognitive aging. SIGNIFICANCE: Given that some theories of cognitive aging
      suggest age-related failure of inhibitory mechanisms may span different
      modalities, the present findings contribute to an alternative view where age
      related declines within each inhibitory modality are unrelated.

PMID- 21963324
TI  - Digestive oncology: It's now or never.

PMID- 21963325
TI  - Does a contralateral carotid occlusion adversely impact carotid artery stenting
      outcomes?
AB  - BACKGROUND: Carotid artery stenting (CAS) has grown as a possible alternative for
      the treatment of extracranial cerebrovascular disease in the past decade. A
      preexisting contralateral carotid artery occlusion has been described as a risk
      factor for inferior outcomes after carotid endarterectomy, but its impact on CAS
      outcomes is less understood. METHODS: A retrospective review of 417 CAS
      procedures performed between May 2001 and July 2010 at a single center using self
      expanding nitinol stents and mechanical embolic protection devices was conducted.
      Patients were divided into two groups, those with a preexisting contralateral
      carotid occlusion (group A, n = 39) versus those without a contralateral
      occlusion (group B, n = 378). Patient demographics and comorbidities as well as
      30-day and late death, stroke, and myocardial infarction (MI) rates were
      analyzed. Mean follow-up was 4 years (range: 0-9.4 years). RESULTS: Overall, mean
      age of the 314 men and 103 women was 70.5 years. In group A, there were two
      (5.1%) octogenarians and nine patients (23.1%) with symptomatic disease as
      compared with group B with 53 (14%) octogenarians and 121 (32%) patients with
      symptomatic disease. The overall 30-day death, stroke, and MI rates were 0.5%,
      1.9%, and 0.7%, respectively. When comparing group A with group B, these results
      were not significantly different: death (0% vs. 0.5%), stroke (2.6% vs. 1.9%),
      and MI (0% vs. 0.8%). Long-term outcomes for groups A and B were also not
      significantly different: death (25.6% vs. 22.2%), stroke (5.3% vs. 3.4%), and MI
      (15.4% vs. 14%) (p = nonsignificant). CONCLUSION: A preexisting contralateral
      carotid artery occlusion does not seem to adversely impact CAS outcomes.

PMID- 21963326
TI  - Rigorous ablution is a potential risk factor to fatal brain infection in
      developing countries.

PMID- 21963327
TI  - The improvement of hypoxia correlates with neuroanatomic and developmental
      outcomes: comparison of midterm outcomes in infants with transposition of the
      great arteries or single-ventricle physiology.
AB  - OBJECTIVES: We performed a prospective longitudinal study of the neuroanatomic
      and developmental changes in infants with transposition of the great arteries
      (TGA) or single-ventricle (SV) physiology to identify variables in anatomic
      development of the brain associated with functional impairment. METHODS: Thirty
      three infants with congenital heart defects, 23 with SV and 10 with TGA, were
      studied at around 1 year old (time 1) and 3 years old (time 2) by magnetic
      resonance imaging of the brain. Neurodevelomental assessment was performed at the
      same time. RESULTS: The whole and frontal lobe volumes were significantly reduced
      in both groups at time 1 compared with normal control subjects (P < .01).
      However, by time 2 whole and frontal brain volumes were normal in the TGA group
      but remained significantly smaller (P < .01) in the SV group. In agreement with
      these findings, the mental development index (MDI) was lower (P < .05) at time 1
      in both groups but improved to normal levels at time 2 in the TGA group. In the
      SV group, both MDI and the psychomotor development index (PDI) were significantly
      decreased at both time 1 and time 2 (P < .01). These patients continued to
      experience hypoxia, and multivariate analysis revealed that functional oxygen
      saturation was significantly associated with PDI. Further, the PDI score
      correlated with whole and regional brain volumes (P < .05). CONCLUSIONS:
      Neuroanatomic and developmental outcomes improve progressively in infants with
      TGA, unlike those with SV physiology. Impaired cerebral circulation and hypoxia
      may have significant effects on brain growth and development in infants with
      critical congenital heart disease.

PMID- 21963329
TI  - A prospective controlled trial of endobronchial ultrasound-guided transbronchial
      needle aspiration compared with mediastinoscopy for mediastinal lymph node
      staging of lung cancer.
AB  - OBJECTIVE: The study objective was to compare endobronchial ultrasound-guided
      transbronchial needle aspiration (EBUS-TBNA) with mediastinoscopy for mediastinal
      lymph node staging of potentially resectable non-small cell lung cancer. METHODS:
      Patients with confirmed or suspected non-small cell lung cancer who required
      mediastinoscopy to determine suitability for lung cancer resection were entered
      into the trial. All patients underwent EBUS-TBNA followed by mediastinoscopy
      under general anesthesia. If both were negative for N2 or N3 disease, the patient
      underwent pulmonary resection and mediastinal lymphadenectomy. RESULTS: Between
      July 2006 and August 2010, 190 patients were registered in the study, 159
      enrolled, and 153 were eligible for analysis. EBUS-TBNA and mediastinoscopy
      sampled an average of 3 and 4 lymph node stations per patient, respectively. The
      mean short axis of the lymph node biopsied by EBUS-TBNA was 6.9 +/- 2.9 mm. The
      prevalence of N2/N3 disease was 35% (53/153). There was excellent agreement
      between EBUS-TBNA and mediastinoscopy for mediastinal staging in 136 patients
      (91%; Kappa, 0.8; 95% confidence interval, 0.7-0.9). Specificity and positive
      predictive value for both techniques were 100%. The sensitivity, negative
      predictive value, and diagnostic accuracy for mediastinal lymph node staging for
      EBUS-TBNA and mediastinoscopy were 81%, 91%, 93%, and 79%, 90%, 93%,
      respectively. No significant differences were found between EBUS-TBNA and
      mediastinoscopy in determining the true pathologic N stage (McNemar's test, P =
      .78). There were no complications from EBUS-TBNA. Minor complications from
      mediastinoscopy were observed in 4 patients (2.6%). CONCLUSIONS: EBUS-TBNA and
      mediastinoscopy achieve similar results for the mediastinal staging of lung
      cancer. As performed in this study, EBUS-TBNA can replace mediastinoscopy in
      patients with potentially resectable non-small cell lung cancer.

PMID- 21963330
TI  - The change probability effect: incidental learning, adaptability, and shared
      visual working memory resources.
AB  - Statistical properties in the visual environment can be used to improve
      performance on visual working memory (VWM) tasks. The current study examined the
      ability to incidentally learn that a change is more likely to occur to a
      particular feature dimension (shape, color, or location) and use this information
      to improve change detection performance for that dimension (the change
      probability effect). Participants completed a change detection task in which one
      change type was more probable than others. Change probability effects were found
      for color and shape changes, but not location changes, and intentional strategies
      did not improve the effect. Furthermore, the change probability effect developed
      and adapted to new probability information quickly. Finally, in some conditions,
      an improvement in change detection performance for a probable change led to an
      impairment in change detection for improbable changes.

PMID- 21963331
TI  - Setting the stage subliminally: unconscious context effects.
AB  - An important approach to understand how the brain gives rise to consciousness is
      to probe the depth of unconscious processing, thus to define the key features
      that cause conscious awareness. Here, we investigate the possibility for
      subliminal stimuli to shape the context for unconscious processing. Context
      effects have generally been assumed to require consciousness. In the present
      experiment, unconscious context processing was investigated by looking at the
      impact of the context on the response activation elicited by a subliminal prime.
      We compared the effects of the same subliminal prime on target processing when
      the prime was embedded in different unconscious contexts. Results showed that the
      same prime can evoke opposite responses depending on the unconscious context in
      which it is presented. Taken together, the results of this study show that
      context effects can be unconscious.

PMID- 21963332
TI  - The effects of general and alcohol-specific peer factors in adolescence on
      trajectories of alcohol abuse disorder symptoms from 21 to 33 years.
AB  - BACKGROUND: The present study examines whether general and alcohol-specific peer
      risk factors from age 10 to 18 are associated with longitudinal patterns of adult
      alcohol abuse disorder symptoms from age 21 to 33. METHODS: Using growth mixture
      modeling, trajectory groups of alcohol abuse disorder symptoms from age 21 to 33
      were identified. We then examined the relationships between the identified
      trajectory groups of alcohol abuse disorder symptoms and respondents' own
      adolescent binge drinking, a general negative peer factor, and an alcohol
      specific peer factor (having drinking peers) in adolescence using pseudo-class
      Wald Chi-square tests, and multinomial logistic regressions. RESULTS: Four
      different trajectory groups of alcohol abuse disorder symptoms were identified:
      persistor group (3%), decreaser group (23%), escalator group (3%), and a no
      disorder group (71%). Bivariate Wald Chi-square tests indicated that adolescent
      binge drinking behavior and general and alcohol-specific peer factors
      differentiated the adult alcohol abuse trajectory groups. Multivariate
      multinomial logistic regression showed that the general negative peer factors
      distinguished those who later persisted in alcohol abuse from those who desisted
      (i.e., persistor group vs. decreaser group) during young adulthood, even after
      adjusting for respondents' adolescent binge drinking. On the other hand,
      associating with drinking peers did not distinguish these trajectories.
      CONCLUSION: Alcohol-specific peer influences appear to influence alcohol abuse
      disorder symptoms in the early 20s, while general negative peer exposure in
      adolescence increases in importance as a risk factor for alcohol abuse disorder
      symptom persistence in the late 20s and the early 30s.

PMID- 21963334
TI  - Low-dose dental irradiation decreases oxidative stress in osteoblastic MC3T3-E1
      cells without any changes in cell viability, cellular proliferation and cellular
      apoptosis.
AB  - Cellular responses following low-dose irradiation have been widely debated.
      Several studies have revealed detrimental effects of low-dose irradiation;
      however, some studies have shown contrasting results. Moreover, the effects of
      periapical irradiation on osteoblastic cells have not yet been revealed.
      Therefore, in this study, we tested the hypothesis that low-dose dental
      irradiation of osteoblastic cells reduces reactive oxygen species (ROS)
      production and leads to increased cellular proliferation and high-dose dental
      irradiation of osteoblastic cells increases ROS production and leads to cellular
      apoptosis. METHODS: We irradiated MC3T3-E1 cells with various doses of periapical
      irradiation (0, 1, 2, 5 and 10 doses, 1.5 mGy/dose). We evaluated cell viability
      using MTT assay, the expression of Bax and Bcl-2, as markers for apoptosis and
      the expression of cyclin D1 as a marker for cell proliferation 24h after each
      irradiation. We also measured ROS production 4h following each irradiation.
      RESULTS: ROS production was significantly reduced after one dose of periapical
      irradiation (1.5 mGy); however, after 10 doses (15 mGy), ROS production was
      significantly increased (p<0.05). None of the doses of dental radiation affected
      cell viability as determined by MTT assay, nor did they change the apoptotic
      marker: (the Bax/Bcl-2 ratio). However, 10 doses of dental irradiation
      significantly decreased the expression of cyclin D1. CONCLUSIONS: Our findings
      suggest that low-dose dental radiation may help to detoxify osteoblastic cells by
      reducing ROS production without any changes in cell viability, cellular apoptosis
      or proliferation. However, high-dose dental radiation impairs osteoblastic
      proliferation via increase ROS production without any changes in cell viability
      or apoptotic responses.

PMID- 21963333
TI  - Analyses related to the development of DSM-5 criteria for substance use related
      disorders: 2. Proposed DSM-5 criteria for alcohol, cannabis, cocaine and heroin
      disorders in 663 substance abuse patients.
AB  - BACKGROUND: A number of changes have been proposed and investigated in the
      criteria for substance use disorders in DSM-5. However, although clinical utility
      of DSM-5 is a high priority, relatively little of the empirical evidence
      supporting the changes was obtained from samples of substance abuse patients.
      METHODS: Proposed changes were examined in 663 patients in treatment for
      substance use disorders, evaluated by experienced clinicians using the
      Psychiatric Research Interview for Substance and Mental Disorders (PRISM). Factor
      and item response theory analysis was used to investigate the dimensionality and
      psychometric properties of alcohol, cannabis, cocaine and heroin abuse and
      dependence criteria, and craving. RESULTS: The seven dependence criteria, three
      of the abuse criteria (hazardous use; social/interpersonal problems related to
      use; neglect of roles to use), and craving form a unidimensional latent trait for
      alcohol, cannabis, cocaine and heroin. Craving did not add significantly to the
      total information offered by the dependence criteria, but adding the three abuse
      criteria and craving together did significantly increase total information for
      the criteria sets associated with alcohol, cannabis and heroin. CONCLUSION: Among
      adult patients in treatment for substance disorders, the alcohol, cannabis,
      cocaine and heroin criteria for dependence, abuse (with the exception of legal
      problems), and craving measure a single underlying dimension. Results support the
      proposal to combine abuse and dependence into a single diagnosis in the DSM-5,
      omitting legal problems. Mixed support was provided for the addition of craving
      as a new criterion, warranting future studies of this important construct in
      substance use disorders.

PMID- 21963335
TI  - Effects of biglycan on physico-chemical properties of ligament-mineralized tissue
      attachment sites.
AB  - Matrix proteoglycans define matrix structure, mineralization, and resulting
      biomechanics of tissues and their attachment sites. OBJECTIVE: We therefore
      investigated physical and (bio)chemical differences in enamel and periodontal
      tissues/attachment sites from mice that lack a specific nanoscale small leucine
      rich proteoglycan (SLRPs) named biglycan (BGN). DESIGN: Experimental groups
      consisted of N=4, biglycan knockout (BGNKO) and N=5 wildtype (WT) 8-week-old,
      male C3H mice. Morphology, histochemical and mechanical analyses were performed
      through micro X-ray computed tomography (Micro XCTTM), immunohistochemistry, and
      microindentation. Unless mentioned otherwise, all differences between BGNKO and
      WT were demonstrated to be statistically significant through Student's t-tests
      with a 95% confidence interval (P<=0.05). RESULTS: Histomorphometry performed by
      using Micro XCTTM images indicated significantly higher BGNKO-enamel (0.46 +/-
      0.03mm(3)) and BGNKO-root (1.81 +/- 0.10mm(3)) volumes compared to WT-enamel
      (0.37 +/- 0.02mm(3)) and WT-root (1.65 +/- 0.07mm(3)). BGNKO tooth size was
      relatively larger than WT mice, with no significant difference between skull
      sizes. Immunohistochemistry indicated BGN expression in the periodontal ligament
      (PDL), alveolar bone (AB), at the bone-PDL and cementum-PDL attachment sites in
      WT mice. Deeper AB resorption pits within interdental region of BGNKO specimens
      compared to WT resulting in significant differences in PDL-space of BGNKO (93 +/-
      13MUm) and WT (74 +/- 11MUm) were observed. Microhardness of BGNKO-enamel (2.46
      +/- 0.60GPa) and BGNKO-AB (0.52 +/- 0.10GPa) was significantly lower than WT
      enamel (2.67 +/- 0.60GPa) and WT-AB (0.54 +/- 0.10GPa). CONCLUSION: Results
      indicate that BGNKO-mice exhibit significant differences in tissue properties
      compared to WT-mice.

PMID- 21963336
TI  - Hydrogen production from food wastes and gas post-treatment by CO2 adsorption.
AB  - The production of H(2) by biological means, although still far from being a
      commercially viable proposition, offers great promise for the future.
      Purification of the biogas obtained may lead to the production of highly
      concentrated H(2) streams appropriate for industrial application. This research
      work evaluates the dark fermentation of food wastes and assesses the possibility
      of adsorbing CO(2) from the gas stream by means of a low cost biomass-based
      adsorbent. The reactor used was a completely stirred tank reactor run at
      different hydraulic retention times (HRTs) while the concentration of solids of
      the feeding stream was kept constant. The results obtained demonstrate that the
      H(2) yields from the fermentation of food wastes were affected by modifications
      in the hydraulic retention time (HRT) due to incomplete hydrolysis. The decrease
      in the duration of fermentation had a negative effect on the conversion of the
      substrate into soluble products. This resulted in a lower amount of soluble
      substrate being available for metabolisation by H(2) producing microflora leading
      to a reduction in specific H(2) production. Adsorption of CO(2) from a gas stream
      generated from the dark fermentation process was successfully carried out. The
      data obtained demonstrate that the column filled with biomass-derived activated
      carbon resulted in a high degree of hydrogen purification. Co-adsorption of H(2)S
      onto the activated carbon also took place, there being no evidence of H(2)S
      present in the bio-H(2) exiting the column. Nevertheless, the concentration of
      H(2)S was very low, and this co-adsorption did not affect the CO(2) capture
      capacity of the activated carbon.

PMID- 21963337
TI  - Barriers towards achieving a zero waste society.

PMID- 21963338
TI  - Fate of metals contained in waste electrical and electronic equipment in a
      municipal waste treatment process.
AB  - In Japan, waste electrical and electronic equipment (WEEE) that is not covered by
      the recycling laws are treated as municipal solid waste. A part of common metals
      are recovered during the treatment; however, other metals are rarely recovered
      and their destinations are not clear. This study investigated the distribution
      ratios and substance flows of 55 metals contained in WEEE during municipal waste
      treatment using shredding and separation techniques at a Japanese municipal waste
      treatment plant. The results revealed that more than half of Cu and most of Al
      contained in WEEE end up in landfills or dissipate under the current municipal
      waste treatment system. Among the other metals contained in WEEE, at least 70% of
      the mass was distributed to the small-grain fraction through the shredding and
      separation and is to be landfilled. Most kinds of metals were concentrated
      several fold in the small-grain fraction through the process and therefore the
      small-grain fraction may be a next target for recovery of metals in terms of both
      metal content and amount. Separate collection and pre-sorting of small digital
      products can work as effective way for reducing precious metals and less common
      metals to be landfilled to some extent; however, much of the total masses of
      those metals would still end up in landfills and it is also important to consider
      how to recover and utilize metals contained in other WEEE such as audio/video
      equipment.

PMID- 21963339
TI  - Non-invasive urinary screening for aromatic L-amino acid decarboxylase deficiency
      in high-prevalence areas: a pilot study.
AB  - BACKGROUND: The diagnosis of aromatic L-amino acid decarboxylase (AADC)
      deficiency, one of the pediatric neurotransmitter disorders, is classically made
      with plasma enzyme level or cerebrospinal fluid (CSF) neurotransmitter profile,
      while both are technically demanding and the latter requires the invasive lumbar
      puncture. So far less than 100 cases have been reported worldwide with 20% from
      Taiwan. It was postulated that the condition might have been under-diagnosed
      among Chinese populations and a non-invasive screening tool should be developed
      in areas with high prevalence. METHODS: Urine metabolic profiles performed by gas
      chromatography-mass spectrometry (GC-MS) in a 31-month period were
      retrospectively reviewed: those with vanilmandelic acid concentration lower than
      one percentile plus the presence of 3-o-methyldopa were defined as positive and
      the patients were further evaluated. RESULTS: Among 1046 metabolic profiles (from
      845 patients) reviewed, 3 profiles from 2 patients were screened positive: both
      cases had compatible CSF neurotransmitter profiles and the diagnosis was further
      confirmed by genetic analysis of DDC gene. 13 negative urinary metabolic profiles
      from 7 patients who had CSF neurotransmitters analyzed were identified as
      controls: all 7 CSF neurotransmitter profiles were not compatible for AADC
      deficiency. CONCLUSIONS: The GC-MS-based urine metabolic profiling was shown to
      be a satisfactory screening tool for AADC deficiency. Further confirmation can be
      performed by mutation analysis in the DDC gene, thus avoiding risks of lumbar
      puncture. We advocate all ethnic Chinese patients presenting with dystonia have
      their urine organic acids analyzed before proceeding to CSF neurotransmitters
      analysis.

PMID- 21963340
TI  - Facile syntheses of the disaccharide repeating unit of the O-antigenic
      polysaccharide of Burkholderia pseudomallei strain 304b and its dimer and trimer.
AB  - A highly efficient strategy for the preparation of a disaccharide-repeating unit
      of the O-antigenic polysaccharide of Burkholderia pseudomallei strain 304b, and
      its dimer and trimer, has been developed through a regio- and stereoselective
      manner using p-methoxylphenyl 2,4,6-tri-O-benzoyl-alpha-D-glucopyranoside and 3-O
      allyloxycarbonyl-2,4-di-O-benzoyl-6-deoxy-alpha-L-talopyranosyl
      trichloroacetimidate as the key synthons. The target molecules were equipped with
      a p-methoxylphenyl handle at the reducing terminus to allow for their further
      functionalization and attachment to a carrier protein.

PMID- 21963341
TI  - Purification and characterization of a lectin with antiproliferative activity
      toward cancer cells from the dried fruit bodies of Lactarius flavidulus.
AB  - The isolation of a dimeric 29.8-kDa lectin (LFL) from dried Lactarius flavidulus
      fruit bodies is reported herein. The chromatographic procedure utilized comprised
      anion-exchange chromatography on DEAE-cellulose, cation-exchange chromatography
      on CM-cellulose, anion-exchange chromatography on SP-Sepharose, and gel
      filtration by fast protein liquid chromatography on Superdex 75. The
      hemagglutinating activity of LFL was inhibited by a variety of simple sugars,
      such as lactose, p-nitrophenyl alpha-D-glucopyranoside, p-nitrophenyl beta-D
      glucopyranoside and inositol, and by the polysaccharide inulin. The activity of
      LFL was stable up to 40 degrees C. There was a precipitous drop in activity when
      the temperature was elevated to 50 degrees C. Hemagglutinating activity was
      retained when LFL was exposed to 6.25-12.5 mM HCl and NaOH. The activity was
      potently inhibited by Fe(2+) and Fe(3+) ions, and slightly inhibited by Al(3+)
      and Mn(2+) ions. LFL suppressed the proliferation of hepatoma (HepG2) and
      leukemic (L1210) cells with an IC(50) of 8.90 and 6.81 MUM, respectively. It
      inhibited the activity of human immunodeficiency virus type 1 (HIV-1) reverse
      transcriptase (RT) with an IC(50) of 5.68 MUM. However, LFL did not exhibit
      antifungal activity.

PMID- 21963342
TI  - Characterization of the lipopolysaccharide O-antigen of Cronobacter turicensis
      HPB3287 as a polysaccharide containing a 5,7-diacetamido-3,5,7,9-tetradeoxy-D
      glycero-D-galacto-non-2-ulosonic acid (legionaminic acid) residue.
AB  - Cronobacter turicensis, previously known as Enterobacter sakazakii, is a Gram
      negative opportunistic food-borne pathogen that has been reported as a cause of
      life-threatening neonatal infections. From chemical and physical analyses
      involving composition analysis, methylation, two-dimensional high-resolution
      nuclear magnetic resonance, and mass spectrometry methods, the antigenic O
      polysaccharide in the smooth-type lipopolysaccharide of C. turicensis (strain HPB
      3287) was determined to be a high molecular mass polymer of a repeating
      pentasaccharide unit composed of D-galactose, D-glucose, 2-acetamido-2-deoxy-D
      galactose, and 5,7-diacetamido-3,5,7,9-tetradeoxy-D-glycero-D-galacto-non-2
      ulosonic acid (legionaminic acid), in a molar ratio 2:1:1:1, and having the
      structure: [see formula in text].

PMID- 21963343
TI  - Formalin-induced iatrogenic cellulitis: a rare case of dental negligence.

PMID- 21963344
TI  - Parallel speciation in Astyanax cave fish (Teleostei) in Northern Mexico.
AB  - We investigated differentiation processes in the Neotropical fish Astyanax that
      represents a model system for examining adaptation to caves, including regressive
      evolution. In particular, we analyzed microsatellite and mitochondrial data of
      seven cave and seven surface populations from Mexico to test whether the
      evolution of the cave fish represents a case of parallel evolution. Our data
      revealed that Astyanax invaded northern Mexico across the Trans-Mexican Volcanic
      Belt at least three times and that populations of all three invasions adapted to
      subterranean habitats. Significant differentiation was found between the cave and
      surface populations. We did not observe gene flow between the strongly eye and
      pigment reduced old cave populations (Sabinos, Tinaja, Pachon) and the surface
      fish, even when syntopically occurring like in Yerbaniz cave. Little gene flow,
      if any, was found between cave populations, which are variable in eye and
      pigmentation (Micos, Chica, Caballo Moro caves), and surface fish. This suggests
      that the variability is due to their more recent origin rather than to
      hybridization. Finally, admixture of the young Chica cave fish population with
      nuclear markers from older cave fish demonstrates that gene flow between
      populations that independently colonized caves occurs. Thus, all criteria of
      parallel speciation are fulfilled. Moreover, the microsatellite data provide
      evidence that two co-occurring groups with small sunken eyes and externally
      visible eyes, respectively, differentiated within the partly lightened Caballo
      Moro karst window cave and might represent an example for incipient sympatric
      speciation.

PMID- 21963345
TI  - Prognosis of acute invasive fungal rhinosinusitis related to underlying disease.
AB  - BACKGROUND: Acute invasive fungal rhinosinusitis (AIFRS) is a rare disease with
      high morbidity and mortality rates. The objective of this study was to correlate
      the initial clinical features of AIFRS to the prognosis after surgery. METHODS:
      Thirty-two patients with AIFRS were evaluated retrospectively. The correlation of
      underlying disease, fungus isolated, and extent of the disease to the clinical
      outcome of AIFRS was also evaluated. RESULTS: The most common underlying disease
      was hematological malignancy and aplasia (n=20). Aspergillus (n=13) and
      Mucoraceae (n=11) were the main fungi found in AIFRS. Mucosal biopsy confirmed
      fungal invasion to the nasal mucosa in all cases. Computed tomography and
      endoscopic findings showed a predominance of unilateral disease, with various
      stages of nasal involvement. All patients underwent surgical debridement and
      systemic antifungal therapy immediately after diagnosis. Sixteen patients died
      (50%) due to AIFRS. A poor prognosis was related to the extensiveness of AIFRS
      and to the underlying disease (patients with aplastic anemia and diabetes had the
      worst outcomes), but not to the fungus isolated. CONCLUSIONS: Early medical and
      surgical treatment is essential to improve the prognosis of AIFRS patients. A
      poorer prognosis was associated with underlying disease and extensiveness of
      AIFRS, but not to the fungus isolated.

PMID- 21963346
TI  - Beneficial effects of a strain of Lactobacillus paracasei subsp. paracasei in
      Staphylococcus aureus-induced intestinal and colonic injury.
AB  - OBJECTIVES: The aim of this study was to investigate the in vitro and in vivo
      anti-staphylococcal activity of a lactic acid bacterial strain and its effect on
      the intestinal histological damage caused by Staphylococcus aureus infection.
      METHODS: Lactobacillus paracasei subsp. paracasei was isolated in our laboratory
      from breastfed newborn feces and identified phenotypically and genotypically. The
      strain was analyzed by spot-on-lawn and well diffusion assays for the production
      of bacteriocins against five antibiotic-resistant S. aureus strains isolated from
      the feces of hospitalized patients with antibiotic-associated diarrhea. The anti
      staphylococcal activity of this strain was evaluated in fermented milk and in
      vivo using holoxenic rabbits. RESULTS: The strain was able to produce a
      bacteriocin-like substance active against the staphylococcal strains. A reduction
      of 2 log in S. aureus cell numbers was registered in co-culture with L. paracasei
      in fermented milk. Administration of skimmed milk containing S. aureus (10(7)
      cells/ml) to healthy rabbits induced a persistent diarrheal state 5 days after
      the challenge. Dissection of the rabbits and consequent histological observations
      showed damage and an atrophy of the intestinal and colonic mucosae of the
      diarrheal rabbits; in contrast an arrest of the diarrhea concomitant with
      recovery of the intestinal villi and the colonic crypts was observed in the
      rabbits treated with L. paracasei-fermented milk. Furthermore, the diarrheal
      state persisted in spite of a decrease in the level of S. aureus cells in the
      feces of the rabbits receiving sterile milk; this was in contrast to the rabbits
      treated with L. paracasei-fermented milk, in which the decrease in the S. aureus
      fecal number was associated with the arrest of the diarrhea. CONCLUSIONS: L.
      paracasei could act as a potential barrier to prevent S. aureus- associated
      injury and might exert its effect on the staphylococcal enterotoxins or their
      target.

PMID- 21963347
TI  - Wolf-pack (Canis lupus) hunting strategies emerge from simple rules in
      computational simulations.
AB  - We have produced computational simulations of multi-agent systems in which wolf
      agents chase prey agents. We show that two simple decentralized rules controlling
      the movement of each wolf are enough to reproduce the main features of the wolf
      pack hunting behavior: tracking the prey, carrying out the pursuit, and
      encircling the prey until it stops moving. The rules are (1) move towards the
      prey until a minimum safe distance to the prey is reached, and (2) when close
      enough to the prey, move away from the other wolves that are close to the safe
      distance to the prey. The hunting agents are autonomous, interchangeable and
      indistinguishable; the only information each agent needs is the position of the
      other agents. Our results suggest that wolf-pack hunting is an emergent
      collective behavior which does not necessarily rely on the presence of effective
      communication between the individuals participating in the hunt, and that no
      hierarchy is needed in the group to achieve the task properly.

PMID- 21963348
TI  - Synthesis, preliminary biological evaluation and molecular modeling of some new
      heterocyclic inhibitors of TACE.
AB  - Central heteroaryl ring analogues belonging to a series of potent hydroxamate
      TACE inhibitors were synthesized. The TACE inhibitory activities of these
      compounds were evaluated by in vitro WBA and in silico molecular modeling studies
      using crystal structure of human TACE. Compound 14 showed very good in vitro
      inhibition, supported by the in silico docking studies.

PMID- 21963350
TI  - Interactions of the serotonin and circadian systems: nature and nurture in
      rhythms and blues.
AB  - The serotonin and circadian systems are principal regulatory networks of the
      brain. Each consists of a unique set of neurons that make widespread neural
      connections and a defined gene network of transcriptional regulators and
      signaling genes that subserve serotonergic and circadian function at the genetic
      level. These master regulatory networks of the brain are extensively intertwined,
      with reciprocal circuit connections, expression of key genetic elements for
      serotonin signaling in clock neurons and expression of key clock genes in
      serotonergic neurons. The reciprocal connections of the serotonin and circadian
      systems likely have importance for neurobehavioral disorders, as suggested by
      their convergent contribution to a similar range of mood disorders including
      seasonal affective disorder (SAD), bipolar disorder, and major depression, and as
      suggested by their overlapping relationship with the developmental disorder,
      autism spectrum disorder. Here we review the neuroanatomical and genetic basis
      for serotonin-circadian interactions in the brain, their potential relationship
      with neurobehavioral disorders, and recent work examining the effects on the
      circadian system of genetic perturbation of the serotonergic system as well as
      the molecular and behavioral effects of developmental imprinting of the circadian
      system with perinatal seasonal light cycles.

PMID- 21963349
TI  - Contributions of mature granule cells to structural plasticity in temporal lobe
      epilepsy.
AB  - During the development of epilepsy in adult animals, newly generated granule
      cells integrate abnormally into the hippocampus. These new cells migrate to
      ectopic locations in the hilus, develop aberrant basal dendrites, contribute to
      mossy fiber sprouting, and exhibit changes in apical dendrite structure and
      dendritic spine number. Mature granule cells do not appear to exhibit migration
      defects, basal dendrites, and mossy fiber sprouting, but whether they exhibit
      apical dendrite abnormalities or spine changes is not known. To address these
      questions, we examined the apical dendritic structure of bromodeoxyuridine (Brdu)
      birthdated, green fluorescent protein (GFP)-expressing granule cells born 2
      months before pilocarpine-induced status epilepticus. In contrast to immature
      granule cells, exposing mature granule cells to status epilepticus did not
      significantly disrupt the branching structure of their apical dendrites. Mature
      granule cells did, however, exhibit significant reductions in spine density and
      spine number relative to age-matched cells from control animals. These data
      demonstrate that while mature granule cells are resistant to developing the gross
      structural abnormalities exhibited by younger granule cells, they show similar
      plastic rearrangement of their dendritic spines.

PMID- 21963351
TI  - Animal models of multiple system atrophy.
AB  - Multiple system atrophy (MSA) is a sporadic adult-onset neurodegenerative
      disorder clinically characterized by a variable combination of dysautonomia,
      levodopa-unresponsive parkinsonian and cerebellar symptoms. Neurodegeneration in
      MSA occurs in the substantia nigra, putamen, inferior olive, pontine and
      brainstem nuclei, as well as intermediolateral cell column of the spinal cord.
      MSA is recognized as a synucleinopathy due to the accumulation of insoluble alpha
      synuclein in oligodendroglial cytoplasmic inclusions. Several animal models have
      been developed in order to reproduce various clinical and pathological features
      of MSA. Using "double toxin-double lesion" or "single toxin-double lesion",
      neurotoxin-based models were designed in rats, mice and non-human primates to
      reproduce the neuropathology of MSA in the nigrostriatal system while gene-based
      models were developed in mice to reproduce the accumulation of insoluble alpha
      synuclein in oligodendrocytes. Both approaches have then been merged to create
      optimized, dual-hit models. This review describes the different animal models of
      MSA, their respective advantages and limitations and their usefulness to decipher
      the pathophysiology of MSA then to define efficient symptomatic and disease
      modifying therapies. This article is part of a Special Issue entitled:
      Neuroscience Disease Models.

PMID- 21963352
TI  - Transient activation of midbrain dopamine neurons by reward risk.
AB  - Dopamine neurons of the ventral midbrain are activated transiently following
      stimuli that predict future reward. This response has been shown to signal the
      expected value of future reward, and there is strong evidence that it drives
      positive reinforcement of stimuli and actions associated with reward in accord
      with reinforcement learning models. Behavior is also influenced by reward
      uncertainty, or risk, but it is not known whether the transient response of
      dopamine neurons is sensitive to reward risk. To investigate this, monkeys were
      trained to associate distinct visual stimuli with certain or uncertain volumes of
      juice of nearly the same expected value. In a choice task, monkeys preferred the
      stimulus predicting an uncertain (risky) reward outcome. In a Pavlovian task, in
      which the neuronal responses to each stimulus could be measured in isolation, it
      was found that dopamine neurons were more strongly activated by the stimulus
      associated with reward risk. Given extensive evidence that dopamine drives
      reinforcement, these results strongly suggest that dopamine neurons can reinforce
      risk-seeking behavior (gambling), at least under certain conditions. Risk-seeking
      behavior has the virtue of promoting exploration and learning, and these results
      support the hypothesis that dopamine neurons represent the value of exploration.

PMID- 21963353
TI  - Mania following addition of hydroxytryptophan to monoamine oxidase inhibitor.
AB  - This case report highlights the risk of nutritional supplements and
      misinformation obtained from the internet particularly for those on monamine
      oxdiase inhibitors (MAOIs). Despite sophisticated medical knowledge, this
      patient, who was taking an MOAI and complying with a tyramine-free diet, used a
      supplement of hydroxytryptophan that along with the MAOI appears to have
      precipitated mania, despite no personal or familial history of bipolar disorder.

PMID- 21963355
TI  - De novo synthesis of phospholipids is coupled with autophagosome formation.
AB  - Autophagy, the process involved in the breakdown of intracellular proteins and
      organelles, has become an area of great importance in both cell survival and cell
      death. Despite the abundance of information on this topic, persisting issues
      remain about the origin and mechanism of formation of the autophagosomal
      membrane. The endoplasmic reticulum (ER) plays a critical role in the initiation
      of autophagy, especially in the formation of early lipid particles, termed the
      phagophores or the isolation membranes. The bulk, if not all of the lipid
      biosynthetic pathways cease at the level of the ER where the main synthesizing
      enzymes are resident proteins. We postulate that if the initial isolation
      membrane is formed from the locally synthesized lipids at the level of the ER,
      than an increase in the biosynthesis of the bilayer-forming phospholipids
      (phosphatidylcholine-PC, phosphatidylethanolamine-PE, and phosphatidylserine-PS)
      would occur simultaneously with induction of autophagy. As part of the isolation
      membranes, PE conjugates the cytosolic microtubule-associated protein 1 light
      chain 3 (LC3-I), to form LC3-II, the selective autophagosomal protein.
      Phosphatidylinositol-3-kinase (PI3K) action on the ER phosphatidylinositol occurs
      with phospholipid biogenesis, and together they act to contribute to the
      elongation and assembly of the autophagosomal particle.

PMID- 21963354
TI  - Is prolonged stem cell mobilization detrimental for hematopoiesis?
AB  - Multiple hematological side effects have been reported to result from treatment
      with psychoactive phenothiazines. These reported toxicities include leucopenia,
      granulocytopenia, thrombocytopenia, agranulocytosis, and bone marrow aplasia. The
      physiological mechanism causing these potentially life-threatening blood
      dyscrasias is unknown. Recently, we discovered that phenothiazines exhibit
      antagonistic properties towards the VLA-4 integrin, an adhesion molecule that is
      responsible for homing and retention of hematological stem/progenitor cells
      (HSPCs) in the bone marrow. After administration of thioridazine we detected
      rapid mobilization of HSPCs into the peripheral blood. We propose that in
      patients receiving phenothiazines over a prolonged time period, continuous
      mobilization of stem cells out of the stem cell niche, results in a disorder of
      hematopoiesis. Furthermore, we also postulate that such cytopenias are caused by
      a loss of the niche environment, which is known to be essential for stem cell
      maintenance.

PMID- 21963356
TI  - Dopamine receptor DRD3 codes for trait aggression as Mendelian recessive.
AB  - The dopamine receptor gene DRD3 and in particular the single nucleotide
      polymorphism Ser9Gly has been extensively investigated and found to have
      potential association with a wide variety of conditions. These include essential
      tremor, unipolar and bipolar depression, as well as a loose association with
      schizophrenia. Evaluation of (1) these known associations with DRD3, (2) the
      recent finding of Costas and colleagues that a haplotype containing Ser-9 is
      associated with protection from schizophrenia, and (3) an extant trait model of
      personality, leads to the hypothesis that an allele DRD3/Ser codes for trait
      aggression by Mendelian recessive inheritance. The implications of this
      hypothesis are that (1) DRD3 is a pleiotropic gene having allelic polymorphism
      related to both behavior and disease, and (2) models of personality based on
      genetic traits hold promise. In the area of schizophrenia, the hypothesis implies
      that schizophrenic patients can be divided into two broad classes: those having
      genotype DRD3/Ser/Ser and those who lack this homozygosity. The hypothesis of the
      association of DRD3 with trait aggression could be readily evaluated by testing
      groups of healthy individuals by personality inventory focused on aggression and
      by biochemical assay of neurotransmitter levels.

PMID- 21963357
TI  - Healthcare workers' compliance with universal precautions in Turkey.
AB  - Blood-borne pathogens (BBP) represent remarkable occupational risks for
      healthcare workers (HCWs). Avoiding occupational blood exposure is a basis of
      prevention of the blood-borne pathogens (BBP). The effectiveness of the
      prevention strategies depends on the compliance and adherence to the program by
      healthcare-facility personnel. The aim of this study was to evaluate Turkish
      HCWs' compliance with Universal Precautions (UP). An analytic, cross-sectional,
      countrywide survey study was performed in hospital settings, (n = 5145) in 30
      hospitals in 19 cities. In total, 1726 of the 5143 (33.6%) participants'
      behaviors were accepted as satisfactory for compliance with UP. The hepatitis
      knowledge levels of 2,650 (51.5%) participants were found to be satisfactory. In
      the multivariate analysis, working at a surgical site (P = 0.004), living in a
      rich region (P = .007) and the existence of a health office for HCWs (p = .000)
      were found to be contributor factors for HCWs' compliance with UP. Conversely,
      being a nurse (P = .000) and HBV/HCV carrier status (P = .039) were significant
      preventing predictors for HCWs' compliance with UP. Along with the other well
      known predictive factors, regional economic status and a health office for HCWs
      are contributors for compliance with UP.

PMID- 21963358
TI  - Hypothesis: hyperhomocysteinemia is an indicator of oxidant stress.
AB  - Elevated plasma homocysteine levels are associated with an increased risk of
      atherosclerosis and thrombosis, as well as a variety of other pathologies such as
      birth defects, Alzheimer's disease and other dementias, osteoporosis, diabetes
      and renal disease. Homocysteine metabolism is catalyzed by a number of enzymes
      that require B-vitamins as cofactors, and homocysteine levels are particularly
      responsive to folate status. The predictive power of plasma homocysteine level as
      a risk factor for atherothrombotic orders raised the appealing hypothesis that
      reduction of homocysteine levels by vitamin supplementation might result in a
      commensurate reduction is the risk of atherothrombotic events. Unfortunately,
      most clinical trials failed to show a significant benefit of vitamin
      supplementation on cardiovascular events, in spite of significant lowering of
      plasma homocysteine levels. Thus, it is not clear whether homocysteine actually
      plays a causal role in many pathologies with which it is associated, or whether
      it is instead a marker for some other underlying mechanism. A large body of data
      links hyperhomocysteinemia and folate status with oxidant stress. In this article
      I review data that suggests that homocysteine not only promotes cellular and
      protein injury via oxidant mechanisms, but is also a marker for the presence of
      pathological oxidant stress. Thus, it is possible that hyperhomocysteinemia is
      not a common primary cause of atherothrombotic disorders in the general
      population, but rather a marker of systemic or endothelial oxidant stress that is
      a major mediator of these disorders.

PMID- 21963359
TI  - mTOR in breast cancer: differential expression in triple-negative and non-triple
      negative tumors.
AB  - Triple-negative breast cancer (TNBC) is defined by the absence of estrogen
      receptors (ER), progesterone receptors (PR) and overexpression of HER2. Targeted
      therapy is currently unavailable for this subgroup of breast cancer patients.
      mTOR controls cancer cell growth, survival and invasion and is thus a potential
      target for the treatment of patients with TNBC. Using immunohistochemistry, mTOR
      and p-mTOR were measured in 89 TNBCs and 99 non-TNBCs. While mTOR expression was
      confined to tumor cell cytoplasm, p-mTOR staining was located in the nucleus,
      perinuclear area and in the cytoplasm. Potentially important, was our finding
      that nuclear p-mTOR was found more frequently in triple-negative than non triple
      negative cancers (p < 0.001). These results suggest that mTOR may play a more
      important role in the progression of TNBC compared to non-TNBC. Based on these
      findings, we conclude that mTOR may be a new target for the treatment of triple
      negative breast cancer.

PMID- 21963360
TI  - Moderate sleep restriction in treated older male OSA participants: greater
      impairment during monotonous driving compared with controls.
AB  - OBJECTIVES: To examine the effects on monotonous driving of normal sleep versus
      one night of sleep restriction in continuous positive airway pressure (CPAP)
      treated obstructive sleep apnoea (OSA) patients compared with age matched healthy
      controls. METHODS: Nineteen CPAP treated compliant male OSA patients (OSA-treated
      patients (OPs)), aged 50-75 years, and 20 healthy age-matched controls underwent
      both a normal night's sleep and sleep restriction to 5h (OPs remained on CPAP) in
      a counterbalanced design. All participants completed a 2h afternoon monotonous
      drive in a realistic car simulator. Driving was monitored for sleepiness-related
      minor and major lane deviations, with 'safe' driving time being total time driven
      prior to first major lane deviation. EEGs were recorded continuously, and
      subjective sleepiness ratings were taken at regular intervals throughout the
      drive. RESULTS: After a normal night's sleep, OPs and controls did not differ in
      terms of driving performance or in their ability to assess the levels of their
      own sleepiness, with both groups driving 'safely' for approximately 90 min.
      However, after sleep restriction, OPs had a significantly shorter (65 min) safe
      driving time and had to apply more compensatory effort to maintain their
      alertness compared with controls. They also underestimated the enhanced
      sleepiness. Nevertheless, apart from this caveat, there were generally close
      associations between subjective sleepiness, likelihood of a major lane deviation
      and EEG changes indicative of sleepiness. CONCLUSIONS: With a normal night's
      sleep, effectively treated older men with OSA drive as safely as healthy men of
      the same age. However, after restricted sleep, driving impairment is worse than
      that of controls. This suggests that, although successful CPAP treatment can
      alleviate potential detrimental effects of OSA on monotonous driving following
      normal sleep, these patients remain more vulnerable to sleep restriction.

PMID- 21963361
TI  - Parental-reported snoring from the first month of life and cognitive development
      at 12 months of age.
AB  - OBJECTIVE: The aim of the present study was to evaluate the effect of persistent
      snoring in the first year of life on developmental outcomes. METHODS: As part of
      a longitudinal study of snoring and sleep in infancy, we identified 13 children
      (10 males) who commenced snoring shortly after birth and continued to snore
      frequently (>= 3 nights/week) at 6 and 12 months of age and 78 controls (31
      males) who were reported by parents to never snore in the absence of a cold.
      Infants were assessed with the Bayley Scales of Infant and Toddler Development
      Edition III and parents completed demographic and sleep questionnaires. RESULTS:
      Infants reported to snore frequently from the first month of life and who
      continued to snore frequently until 12 months of age had significantly lower
      cognitive development scores (mean=94.2; SD=3.9) compared to controls
      (mean=100.6; SD=3.7) (F (1, 96)=40 6, p<0.001; eta(p)(2)=0.32). CONCLUSION:
      Persistent frequent snoring from the first month of life was associated with
      lower cognitive development scores at 12 months of age. It is possible that this
      deficit will become worse with age.

PMID- 21963362
TI  - Phosphorylation of mitogen-activated protein kinase in the medial prefrontal
      cortex and the amygdala following memory retrieval or forgetting in developing
      rats.
AB  - We examined neuronal correlates of forgetting in rats by detection of
      phosphorylated mitogen-activated protein kinase (pMAPK) in the medial prefrontal
      cortex (mPFC) and amygdala. In Experiment 1, postnatal day (P)23 and P16 rats
      received paired noise CS-shock US presentations. When tested immediately after
      conditioning, P23 and P16 rats exhibited similar levels of conditioned fear; when
      tested after 2 days, however, P16 rats showed poor CS-elicited freezing relative
      to P23 rats. In Experiment 2, P16 and P23 rats received either paired or unpaired
      CS-US presentations, and then were tested 48 h later. Consistent with Experiment
      1, P16 rats showed forgetting whereas P23 rats exhibited good retention at test.
      Additionally, unpaired groups showed poor CS-elicited freezing at test.
      Immunohistochemistry showed that P23 and P16 rats given paired presentations
      exhibited significant elevation of pMAPK-immunoreactive (ir) neurons in the
      amygdala compared to rats given unpaired presentations. That is, MAPK
      phosphorylation in the amygdala tracked learning history rather than behavioral
      performance at test. In contrast, only the P23-paired group showed an elevated
      number of pMAPK-ir neurons in mPFC, indicating that MAPK phosphorylation in the
      mPFC tracks memory expression. Different test-perfusion intervals were employed
      in Experiment 3, which showed that the developmental dissociation in the pMAPK-ir
      neurons observed in the mPFC in Experiment 2 was not due to age differences in
      the rate of phosphorylation of MAPK. These findings provide initial evidence
      suggesting that while the mPFC is involved in memory retrieval, MAPK
      phosphorylation in the amygdala may be a persisting neural signature of fear
      memory.

PMID- 21963363
TI  - [Acute disseminated encephalomyelitis: epidemiological, clinical, and outcome
      analysis in 16 patients].
AB  - INTRODUCTION: Acute disseminated encephalomyelitis (ADEM) is a rare paediatric
      disease of autoimmune origin. The aim of this study is to estimate its impact in
      our area over the past 10 years and to analyse the clinical, laboratory and
      radiological presentation, as well as study the response to treatment and
      outcome. PATIENTS AND METHODS: A retrospective analysis of cases diagnosed with
      current ADEM criteria. The age and month of the year at onset, sex, family
      history of demyelination, initial symptoms, disease or previous vaccination, CSF
      features, serology, PCR for herpes virus group in blood and CSF, oligoclonal
      bands in CSF, EEG and neuroimaging features of the skull by MRI, the type of
      treatment received and the response were recorded on each of the patients
      diagnosed. RESULTS: There were 16 patients, with a mean age of 5.6 years.
      Male/female: 11/5, with a dominant debut in the colder months of the year,
      predominantly gait disorder, changes in consciousness and seizures. The radiology
      by MRI showed a predominance of multiple lesions in the same T2 stage, in deep
      white matter and lesions in deep grey matter. There were no in blood parameters
      and the CSF was normal in half of the cases. The origin was determined in 7
      cases. CONCLUSIONS: The annual incidence in children under 14 years was estimated
      at 0.64/100,000. The clinical and radiological findings were the basis of
      diagnosis. The human herpes virus 6 was involved in 4 cases. Most patients
      recovered completely.

PMID- 21963364
TI  - Molecular characterization of Swiss Ceratopogonidae (Diptera) and evaluation of
      real-time PCR assays for the identification of Culicoides biting midges.
AB  - Biting midges of the genus Culicoides (Diptera, Ceratopogonidae) are vectors of
      several viruses of veterinary relevance, and they can cause insect bite
      hypersensitivity. As the morphological identification of these tiny insects is a
      difficult task in many cases, alternative approaches are expedient. With the aim
      to develop real-time PCRs, we determined partial mitochondrial cytochrome oxidase
      I gene (mt COI) sequences from 380 Culicoides midges representing three regions
      of Switzerland, namely the Alps, Midland north of the Alps (Atlantic climate),
      and South of the Alps (Mediterranean climate). The same region was also sequenced
      from non-biting midges of the genera Atrichopogon, Brachypogon, Dasyhelea,
      Forcipomyia and Serromyia. A total of 21 Culicoides species were identified by
      morphology. Sequence variability (haplotypes) was observed in all species. For
      each of C. grisescens and C. obsoletus, a novel cryptic species was identified.
      Whereas all individuals of C. grisescens and of the cryptic C. obsoletus species
      (O2) originated only from Alpine sites, the known C. obsoletus (O1) species was
      found in all three regions. Further, a sister taxon to C. pulicaris was
      identified based on the mt COI sequences and named Culicoides sp. Alignments of
      available mtCOI sequences from Ceratopogonidae (GenBank, this study) were used to
      design real-time PCR primers and probes to distinguish C. chiopterus, C. deltus,
      C. dewulfi, C. grisescens (including the cryptic species), C. imicola, C.
      lupicaris, C. obsoletus O1, C. obsoletus O2, C. pulicaris, C. scoticus and
      Culicoides sp. Specificities of primers and probes was tested with cloned targets
      representing 1 to 4 haplotypes of 18 Culicoides spp. and 1 haplotype each from 4
      other Ceratopogonidae. No cross-reactivity was observed when plasmid template
      representing 5 * 10(6) gene copies was tested, but it was evident (Ct values <=
      30) in few instances when plasmid template representing 5 * 10(9) gene copies was
      utilized, the latter corresponding to the total gene copy number (as determined
      in this study) in 20 insects. The sensitivities of two assays (C. imicola, C.
      grisescens) were tested by spiking single insects into pools of 99 or 999,
      randomly selected non-target Ceratopogonidae (with approx. 90% Culicoides
      specimens). In the pools of 100, Ct values were in the range of those obtained
      with single insects when employing 1% of the isolated DNA, whereas the
      sensitivity with the pools of 1000 was low, presumably due to the low DNA
      concentrations obtained with a protocol that seems inadequate for these larger
      pools. Thus, the assays as described are applicable for the specific
      identification of biting midges in small pools. Primers and probes of this study
      were devised to be suitable for multiplexed assays but these evaluations await to
      be performed.

PMID- 21963365
TI  - Dynamic water networks in cytochrome cbb3 oxidase.
AB  - Heme-copper oxidases (HCOs) are terminal electron acceptors in aerobic
      respiration. They catalyze the reduction of molecular oxygen to water with
      concurrent pumping of protons across the mitochondrial and bacterial membranes.
      Protons required for oxygen reduction chemistry and pumping are transferred
      through proton uptake channels. Recently, the crystal structure of the first C
      type member of the HCO superfamily was resolved [Buschmann et al. Science 329
      (2010) 327-330], but crystallographic water molecules could not be identified.
      Here we have used molecular dynamics (MD) simulations, continuum electrostatic
      approaches, and quantum chemical cluster calculations to identify proton transfer
      pathways in cytochrome cbb(3). In MD simulations we observe formation of stable
      water chains that connect the highly conserved Glu323 residue on the proximal
      side of heme b(3) both with the N- and the P-sides of the membrane. We propose
      that such pathways could be utilized for redox-coupled proton pumping in the C
      type oxidases. Electrostatics and quantum chemical calculations suggest an
      increased proton affinity of Glu323 upon reduction of high-spin heme b(3).
      Protonation of Glu323 provides a mechanism to tune the redox potential of heme
      b(3) with possible implications for proton pumping.

PMID- 21963366
TI  - Impedance measurement for real time detection of neuronal cell death.
AB  - Detection of neuronal cell death is a standard requirement in cell culture models
      of neurodegenerative diseases. Although plenty of viability assays are available
      for in vitro applications, most of these are endpoint measurements providing only
      little information on the kinetics of cell death. Here, we validated the
      xCELLigence system based on impedance measurement for real-time detection of cell
      death in a neuronal cell line of immortalized hippocampal neurons (HT-22 cells),
      neuronal progenitor cells (NPC) and differentiated primary cortical neurons. We
      found a good correlation between impedance measurements and endpoint viability
      assays in HT-22 cells and NPC, for detecting proliferation, cell death kinetics
      and also neuroprotective effects of pharmacological inhibitors of apoptosis. In
      primary neurons we could not detect dendritic outgrowth during differentiation of
      the cells. Cell death in primary neurons was detectable by the xCELLigence
      system, however, the changes in the cell index on the basis of impedance
      measurements depended to a great extent on the severity of the insult. Cell death
      induced by ionomycin, e.g. shows as a fast paced process involving a strong
      cellular disintegration, which allows for impedance-based detection. Cell death
      accompanied by less pronounced morphological changes like glutamate induced cell
      death, however, is not well accessible by this approach. In conclusion, our data
      show that impedance measurement is a convenient and reliable method for the
      detection of proliferation and kinetics of cell death in neuronal cell lines,
      whereas this method is less suitable for the assessment of neuronal
      differentiation and viability of primary neurons.

PMID- 21963367
TI  - Simultaneous measurement of membrane potential changes in multiple pattern
      generating neurons using voltage sensitive dye imaging.
AB  - Optical imaging using voltage-sensitive dyes (VSDs) is a promising technique for
      the simultaneous activity recording of many individual neurons. While such
      simultaneous recordings are critical for the understanding of the integral
      functionality of neural systems, functional interpretations on a single neuron
      level are difficult without knowledge of the connectivity of the underlying
      circuit. Central pattern generating circuits, such as the pyloric and gastric
      mill circuits in the stomatogastric ganglion (STG) of crustaceans, allow such
      investigations due to their well-known connectivities and have already
      contributed much to our understanding of general neuronal mechanisms. Here we
      present for the first time simultaneous optical recordings of the pattern
      generating neurons in the STG of two crustacean species using bulk loading of the
      VSD di-4-ANEPPS. We demonstrate the recording of firing activities and synaptic
      interactions of the circuit neurons as well as inter-circuit interactions in
      their functional context, i.e. without artificial stimulation. Neurons could be
      uniquely identified using simple event-triggered averaging. We tested this
      technique in two different species of crustaceans (lobsters and crabs), since
      several crustacean species are used for studying motor pattern generation. The
      signal-to-noise ratio of the optical signal was high enough in both species to
      derive phase-relationship between the network neurons, as well as action
      potentials and excitatory and inhibitory postsynaptic potentials. We argue that
      imaging of neural networks with identifiable neurons with well-known
      connectivity, like in the STG, is crucial for the understanding of emergence of
      network functionality.

PMID- 21963368
TI  - Is there still a future for neurokinin 3 receptor antagonists as potential drugs
      for the treatment of psychiatric diseases?
AB  - Selective non-peptide antagonists for the neurokinin 3 (NK(3)) receptor first
      became available about twenty years ago. Although the understanding of the role
      of the NK(3) receptor in the brain has been greatly complicated by marked species
      differences in its distribution and by pharmacological heterogeneity, studies
      with brain-penetrant non-peptide NK(3) receptor antagonists in animals have
      indicated that these compounds may find utility in a number of psychiatric
      diseases, including schizophrenia, anxiety and depressive disorders. However,
      clinical studies with selective NK(3) receptor antagonists in these psychiatric
      conditions have been disappointing and they were unable to confirm the promising
      therapeutic potential from animal studies, thereby questioning the therapeutic
      utility of these compounds for CNS disorders. The purpose of this article is to
      provide a critical overview of the available data on NK(3) receptor antagonists
      in the psychiatry research and development field, by reviewing the behavioral and
      neurochemical effects of these agents in both preclinical and clinical studies.

PMID- 21963370
TI  - [Developmental outcome of 5-year-old children born to opiate-dependent mothers:
      effects of a multidisciplinary intervention during pregnancy].
AB  - BACKGROUND: Studies on infant outcomes of opiate-dependent pregnant women find a
      high rate of premature mother-child separation and to a lesser extent
      developmental delay. The specific role of in utero heroin exposure in the
      determination of the developmental outcome seems to be less important than the
      home environment. OBJECTIVE: Describe the health and development of 5-year-old
      children whose drug-addict mothers allowed an early multidisciplinary
      intervention (medical and psychological) in the maternity hospital and
      neonatology. PATIENTS AND METHODS: Thirty-seven children (62% of the initial
      cohort) were seen in consultation with their parents. Growth and development was
      compared with a control group of 374 children of the same age. Comparisons were
      made between the children's and parents' state (social, medical, drug addiction,
      etc.) upon discharge from the maternity hospital and 5 years later. A study was
      conducted on those lost to follow-up. RESULTS: The rate of placement in 5 years
      was very low (13%). Seven children showed a developmental delay, 21 no disorder,
      and nine some problems. Anxiety (37%) and overweight (48%) were the only
      disorders differentiating them from the control group. Compliance with the care
      provided in the maternity hospital was the only item significantly related to the
      development of the 5-year-old children (P=0.05). DISCUSSION: The hypothesis of an
      attachment disorder in those with the greatest need is raised. The likely
      relations between the quality of the care in the maternity hospital, mother-child
      relations, and the attrition of the cohort are also discussed. CONCLUSION:
      Management of the symptoms as well as social and psychological care during
      pregnancy and neonatal hospitalization for opiate-dependent pregnant women
      facilitates a long-lasting relation with childhood professionals, avoids court
      ordered placements, and reduces the appearance of developmental disorders in
      these children.

PMID- 21963372
TI  - [Cancers in older children in Brazzaville].

PMID- 21963371
TI  - [Genetic syndromes that mimic congenital infections: report of 2 cases].
AB  - Genetic syndromes that mimic congenital infections must be recognized because of
      the associated risk of recurrence. We describe a male infant who was born with
      the association of intra-uterine growth retardation, microcephaly, intracranial
      calcifications, white matter abnormalities, microphtalmy, bilateral cataract, and
      hearing loss. Congenital cytomegalovirus (CMV) infection was suspected, but
      serologic CMV markers were not decisive (IgG+/IgM-). His half-sister (same
      father) presented a similar phenotype. Therefore, the diagnosis of congenital CMV
      infection was questioned and a genetic hypothesis was suggested. In 1983,
      Baraitser et al. first described two brothers with microcephaly and intracranial
      calcifications and negative TORCH analysis. Later, a number of authors reported
      children in whom detailed investigation failed to objectively confirm an intra
      uterine infective agent. Clinical features include severe postnatal microcephaly,
      seizures, and pronounced developmental arrest. These cases have been considered
      to define a distinct autosomal recessive disorder first named pseudo-Torch
      syndrome. The family described herein is different from the cases previously
      described with a suspected autosomal dominant inheritance, severe ophtalmological
      abnormalities, and unusual brain imaging.

PMID- 21963373
TI  - [Dapsone for chronic skin lesions in 3 children suffering from Henoch-Schonlein
      vasculitis].
AB  - We describe 3 cases of chronic purpuric skin lesions in children suffering from
      systemic vasculitis: 3 children with Henoch-Schonlein purpura. Dapsone was
      introduced when skin lesions were recurrent, extensive, and persistent, due to
      its known ability to act as an anti-IgA and as an anticytotoxic agent against
      polynuclear neutrophils. Fast and complete but purely suspensive healing of skin
      lesions was noted. One child developed methemoglobinemia, a known side-effect of
      dapsone, highlighting the need for adequate prescription and follow-up.

PMID- 21963374
TI  - [An uncommon cause of convulsions revealed in a 4-year-old girl].

PMID- 21963369
TI  - Glutamate abnormalities in obsessive compulsive disorder: neurobiology,
      pathophysiology, and treatment.
AB  - Obsessive compulsive disorder is prevalent, disabling, incompletely understood,
      and often resistant to current therapies. Established treatments consist of
      specialized cognitive-behavioral psychotherapy and pharmacotherapy with
      medications targeting serotonergic and dopaminergic neurotransmission. However,
      remission is rare, and more than a quarter of OCD sufferers receive little or no
      benefit from these approaches, even when they are optimally delivered. New
      insights into the disorder, and new treatment strategies, are urgently needed.
      Recent evidence suggests that the ubiquitous excitatory neurotransmitter
      glutamate is dysregulated in OCD, and that this dysregulation may contribute to
      the pathophysiology of the disorder. Here we review the current state of this
      evidence, including neuroimaging studies, genetics, neurochemical investigations,
      and insights from animal models. Finally, we review recent findings from small
      clinical trials of glutamate-modulating medications in treatment-refractory OCD.
      The precise role of glutamate dysregulation in OCD remains unclear, and we lack
      blinded, well-controlled studies demonstrating therapeutic benefit from glutamate
      modulating agents. Nevertheless, the evidence supporting some important
      perturbation of glutamate in the disorder is increasingly strong. This new
      perspective on the pathophysiology of OCD, which complements the older focus on
      monoaminergic neurotransmission, constitutes an important focus of current
      research and a promising area for the ongoing development of new therapeutics.

PMID- 21963375
TI  - [POPI: a tool to identify potentially inappropriate prescribing practices for
      children].

PMID- 21963376
TI  - [A case of cricoarytenoid ankylosis in juvenile idiopathic arthritis].

PMID- 21963377
TI  - [Parents' and medical employees' accuracy in the estimation of fees for
      consultations and frequent medical procedures].
AB  - PURPOSE: To analyze the accuracy of estimates made by medical staff and parents
      regarding fees for consultations and frequently prescribed medical exams.
      PATIENTS AND METHODS: The questionnaire focused on the value in euros for the
      following: day and night consultation in the pediatric emergency department,
      blood and urine analysis, electrocardiogram, chest and abdominal x-ray, abdominal
      ultrasound, upper digestive endoscopy, CT scan, cerebral MRI (without
      anesthesia), an arm cast, and superficial wound repair. Medical staff belonged to
      different units of the childrens' hospital. The parents interviewed had consulted
      at the pediatric emergency unit. Neither of the two investigators was familiar
      with the fee structure. To avoid inducing a gradation in estimates, questions
      were asked with no pre-established order. To limit the possibility of
      participants discussing the questionnaire with their colleagues or searching for
      the real value, all medical staff members were assessed within a 48-h period.
      RESULTS: The responses of 185 medical employees (23 pediatricians, 28 interns, 81
      nurses, 45 childcare assistants, seven nurse supervisors) and 187 parents were
      analyzed and compared. Less than 25% of the population gave an answer with an
      accepted error of +/- 30%. Parents and hospital staff overestimated costs,
      parents and childcare assistants overestimated more than other medical employees.
      Radiological exams were the most overestimated procedures with the largest
      proportion of the average deviation from normal value: CT scan 850 +/- 1100%,
      cerebral MRI 370 +/- 590%, abdominal x-ray 240 +/- 390%, and chest x-ray 190 +/-
      320%. COMMENT: Part of our societal culture and now a requirement, the right to
      healthcare has a cost. This cost is often overestimated by caregivers and the
      general population. CONCLUSION: Global understanding of the costs related to
      medical care requires educating the population and medical professionals. Medical
      staff should be informed of the real costs of treatment to enable them to manage
      unnecessary costs. There is a balance between justifying the costs of essential
      medical treatment and not using economic constraints as a pretext for denial of
      treatment.

PMID- 21963378
TI  - [Evaluation of pre-travel prevention, except vaccination, in children returning
      from Africa with fever].
AB  - OBJECTIVES: Evaluating the frequency and modalities of transmissible infection
      prevention counseling in children before a stay in tropical or subtropical areas.
      METHODS: Description of the frequency and modalities of transmissible infection
      prevention counseling (except specific vaccination) given prior to travel in
      children attending a tertiary care center in Paris, France, for fever occurring
      within 3 months following a return from Africa. Data were collected
      retrospectively from medical observations and telephone interviews with parents.
      RESULTS: A total of 173 children were included; 98 and 75 returned from sub
      Saharan Africa and North Africa, respectively. Forty-one percent were less than 2
      years old. Eighty-one percent of the children had consulted before leaving. Among
      children who returned from North Africa, the proportion of children who had a
      specific preventive consultation before travel was lower than among children who
      returned from sub-Saharan Africa (respectively, 72.1% versus 94.7%; p<0.001). In
      children having consulted before traveling, specific hygiene and diet advice had
      been given in 72% of cases but less frequently in children who traveled in North
      Africa compared to children who traveled to sub-Saharan Africa (respectively,
      57.8% vs. 92.2%; p<0.001). Among children who returned from North Africa, those
      who had no preventive consultation before travel had febrile gastrointestinal
      infection more frequently than those who had a consultation before traveling
      (p=0.003). CONCLUSION: Although in this study the majority of children traveling
      to Africa receive transmissible infection prevention counseling before the
      travel, prevention could be improved, particularly before a stay in North Africa.

PMID- 21963379
TI  - [Pediatric adder bites].
AB  - Adder bites and their progression to severe envenomations are more frequent in
      children than in adults. AIM: To describe the clinical, biological, and
      therapeutic characteristics of children bitten by adders and to identify risk
      factors associated with severe envenomations corresponding to grades II and III
      of the Audebert et al. classification (Toxicon 1992). MATERIAL AND METHODS: A
      retrospective study was conducted between 2001 and 2009 in the pediatric
      emergency department of a tertiary children's hospital. The data collected were:
      age and sex of children; day and time of admission; day, time, and circumstances
      of the accident; snake identification; bite location; envenomation severity based
      on the Audebert et al. classification; presence of fang marks; prehospital care;
      use of specific immunotherapy (Viperfav((r))), associated treatments; length of
      stay; orientation, progression, and any complications. RESULTS: Fifty-eight
      children were included (43 boys, 15 girls). The mean age was 7.8 +/- 4.1 years
      (range, 1.8-15 years). Bites occurred more often between 12:00 pm and 6:00 pm
      (62%), and were most often located in the lower extremities (77%). The
      classification of envenomation was: 83% low grade (grade 0, absence of
      envenomation, fang marks present; grade I, minor envenomation) and 17% high grade
      (grades II and III, moderate and severe envenomations). All high-grade
      envenomations received specific immunotherapy (Viperfav((r)) F(ab')(2) fragments
      against Vipera aspis, Vipera berus, and Vipera ammodytes). The mean time from
      bite to Viperfav((r)) injection was 23 +/- 11 h (range, 8-36 h). Being bitten on
      the upper extremities (p < 0.001), during the afternoon (p = 0.025), feeling an
      immediate violent pain (p = 0.037), and high initial glycemia (p = 0.016) were
      associated with a significant risk of progressing to high-grade envenomation.
      There was no significant correlation between age, gender, and upper extremity
      bite. In the final model of the multivariate statistical analysis, three factors
      remained associated with this risk: bite location in the upper extremities
      (relative risk [RR] = 60.5 [3.5-1040[; p = 0.005), immediate violent pain (RR =
      21.5 [1.3-364.5[; p = 0.03), and female gender (RR = 17.5 [0.9-320.3[; p =
      0.053). CONCLUSION: A certain number of criteria seem related with a more
      significant risk of progression to high-grade envenomation following an adder
      bite. These results need to be studied on a larger cohort of patients. Bites to
      the upper extremities should be handled with caution because of the association
      with more severe envenomation.

PMID- 21963380
TI  - Vitrification of in vitro produced goat blastocysts: effects of oocyte donor age
      and development stage.
AB  - This study examines the effectiveness of the cryotop vitrification method for the
      cryopreservation of goat blastocysts. To determine the effects of embryo
      development stage and donor age on in vitro survival rates, good-quality
      blastocysts from adult and prepubertal goats were sorted into non-expanded,
      expanded, hatching and completely hatched. In vitro produced (IVP) blastocysts
      were derived from prepubertal goat oocytes by slicing of ovaries from slaughtered
      animals while adult goat oocytes were collected by the laparoscopic ovum pick up
      (LOPU) method. Blastocysts were vitrified/warmed using the cryotop technique.
      Survival rates were determined in terms of blastocoele re-expansion at 3 and 20 h
      post-warming. For prepubertal goats, survival rates at 3h post-warming were
      significantly higher when expanded blastocysts (78.3%) were vitrified/warmed
      compared to hatched blastocysts (57.4%), whereas non-expanded (62.5%) or hatching
      blastocysts (71.4%) showed similar rates. For adult goats, survival rates were
      significantly higher after warming in expanded (36.4%), hatching (75%) or hatched
      (50%) blastocysts when compared to non-expanded (0%) blastocysts. When survival
      rates were assessed at 20 h post-warming, no differences were observed when we
      compared non-expanded (45.8%), expanded (56.5%), hatching (64.3%) and hatched
      (50.5%) blastocysts from prepubertal goats; and for blastocysts from adult goats,
      survival rates were only significantly lower for the non-expanded stage (0%)
      compared to the other stages. For adult versus prepubertal blastocysts at the
      same developmental stage, our data indicate significantly higher survival rates
      at 3 h post-warming for non-expanded and expanded blastocysts from prepubertal
      goats over their counterparts from adult goats. At 20 h post warming, survival
      rates were only higher for non-expanded blastocysts from prepubertal goats versus
      adult goats. Collectively, our data reveal that blastocysts produced in vitro
      from prepubertal goats return similar survival rates regardless of their
      development stage, whereas blastocysts derived from adult goats are best for
      vitrification at the expanded, hatching or hatched stage.

PMID- 21963381
TI  - Long-term ursodeoxycholate improves circulating redox changes in primary biliary
      cirrhotic patients.
AB  - BACKGROUND AND AIMS: Cholestasis is associated with systemic and hepatic
      oxidative and nitrosative stress; in this scenario, the conjugated hydrophilic
      bile salt ursodeoxycholate (UDCA) might play a protective role. METHODS:
      Circulating oxidative and nitrosative stress markers were assessed in patients
      with primary biliary cirrhosis (PBC) before and during UDCA (15-20mg/kg/day)
      therapy. RESULTS: In patients with stage I-II PBC, UDCA improved ALT and alkaline
      phosphatase levels and near normalized serum thioredoxin (1.97 +/- 0.37 vs 2.41
      +/- 0.39 nmol/L), nitrotyrosine (15 +/- 4 vs 22 +/- 7 nmol/L), nitrosothiols (144
      +/- 28 vs 205 +/- 84 nmol/L) and K-18 levels (162 +/- 21 vs 228 +/- 33 U/L).
      Conversely, less marked changes were noted in patients with stages III-IV who
      showed lower thioredoxin (1.01 +/- 0.31 nmol/L), higher nitrosothiols (605 +/- 64
      nmol/L), nitrotyrosine (62 +/- 13 nmol/L) and K-18 levels (521 +/- 57 U/L).
      Overall, thioredoxin was inversely related with nitrotyrosine (r=-0.838, P<0.001)
      and K-18 (r=-0.838, P<0.001) levels. Nitrosothiols and K-18 were linearly and
      significantly related with nitrotyrosine (r=0.862, P<0.001; r=0.894, P<0.001,
      respectively). CONCLUSIONS: Oxidative and nitrosative changes in patients with
      PBC are effectively counteracted by UDCA. The protective effect of UDCA, however,
      are limited to early disease stages and progressively diminishes with ongoing
      cholestasis.

PMID- 21963382
TI  - Relationship between circulating cytokine levels and physical or psychological
      functioning in patients with advanced cancer.
AB  - OBJECTIVE: To investigate the relation between functional impairments of cancer
      patients and circulating cytokines using a multiplex technique. DESIGN AND
      METHODS: 50 patients with cancer were assessed using the quality of life (QOL)
      questionnaire. 27 plasma cytokine levels were determined by using the Bio-Plex
      array system. The relation to QOL scores was assessed using Chi-square test for
      categorical variables and univariate linear regression analysis for cytokine
      levels. RESULTS: Multivariate analysis showed that interleukin-6 (IL-6) level is
      a significant independent determinant of physical (beta=-0.238, P=0.0126) and
      cognitive functioning (beta=-0.462, P=0.0006) and that vascular endothelial
      growth factor (VEGF) level is a significant independent determinant of emotional
      functioning (beta=-0.414, P=0.039). CONCLUSION: This study, in which 27 cytokines
      are simultaneously tested with cutting edge technology, demonstrates that plasma
      IL-6 and VEGF are significant independent determinants of functional impairments
      in patients with cancer.

PMID- 21963383
TI  - Extreme concentrations of high density lipoprotein cholesterol affect the
      calculation of low density lipoprotein cholesterol in the Friedewald formula and
      other proposed formulas.
AB  - OBJECTIVES: To investigate the effect of extreme levels of high density
      lipoprotein cholesterol (HDL-C) in the calculation of low density lipoprotein
      cholesterol (LDL-C) using Friedewald's formula (FF) and other formulas proposed
      recently. DESIGN AND METHODS: Lipoprotein profile was performed in 2603 samples
      with HDL-C <= 20 mg/dL and 1953 samples with HDL-C >= 100 mg/dL. RESULTS:
      Wilcoxon's and Student's t-tests showed significant differences (p<0.001) between
      calculated LDL-C by different formulas and direct determination in the two groups
      of HDL-C values. Passing-Bablok regression and Bland-Altman plot showed
      disagreement for the four formulas studied, except for Vujovic formula in the HLD
      C >= 100 mg/dL group. CONCLUSIONS: Our results suggested that none of the
      formulas under analysis should be used for estimating LDL-C in samples with
      extreme HDL-C concentrations due to absence of statistical correlation with LDL-C
      direct measurement.

PMID- 21963384
TI  - The stability of markers in dried-blood spots for recommended newborn screening
      disorders in the United States.
AB  - OBJECTIVE: We aimed to measure separately the contributions of heat and humidity
      to changes in levels of 34 markers of inborn disorders in dried-blood-spot (DBS)
      samples. DESIGN AND METHODS: We stored paired sets of DBSs at 37 degrees C for
      predetermined intervals in low-humidity and high-humidity environments. Marker
      levels of all samples in each complete sample set were measured in a single
      analytic run. RESULTS: During the 30 +/- 5 day studies, galactose-1-phosphate
      uridyltransferase and biotinidase lost almost 65% of initial activities in low
      humidity storage; most of the degradation in 27 other markers was attributable to
      adverse effects of high-humidity storage; seven markers in DBSs stored at high
      humidity lost more than 90% of initial levels by the end of the study and 4 of
      the 7 lost more than 50% of initial levels within the first week of storage.
      CONCLUSIONS: Minimizing both humidity and temperature in DBS transportation and
      storage environments is essential to maintaining sample integrity.

PMID- 21963386
TI  - SVEP1 promoter regulation by methylation of CpG sites.
AB  - SVEP1 gene encodes a cell adhesion molecule (CAM) that was previously shown to be
      expressed by cells related to skeletal tissues. Here we focus on SVEP1 expression
      regulation in pre-osteoblastic MBA-15 and mammary adenocarcinoma DA3 cells. We
      show that SVEP1 message and protein are highly expressed by MBA-15 when compared
      with DA3 cells. DNA methylation of CpGs sites is an epigenetic mechanism
      associated with gene silencing. Therefore, we analyzed the methylation status of
      a region potentially harbors SVEP1 promoter and further activity alterations
      induced by estrogen (17betaE(2)) and TNFalpha. We also mapped in silico the
      transcription binding sites namely TFIIB, NF-kappaB, ERE, AP1 and Sp1 at the
      putative promoter. Treatments with demethylation reagents, 5'-aza-deoxy-Cytidine
      (5'-aza-dC), or histone deacetylase inhibitor, Trichostatin A (TSA) resulted with
      an elevation of SVEP1 mRNA expression in both cell types. Methylation levels of
      specific CpGs sites located at transcription binding sites were assessed using
      sodium bisulfite genomic DNA sequencing, methylated DNA immunoprecipitation
      (meDIP) and Methylation-Specific PCR (MSP). Our results show that the putative
      promoter of SVEP1 is hypermethylated in DA3- compared with MBA-15 cells, thus
      regulating SVEP1 expression levels. In addition, by affecting SVEP1 promoter
      methylation status, 17betaE(2) and TNFalpha regulate ectopic SVEP1 promoter and
      mRNA expression. Our data sheds light on understanding the cell-type specific
      promoter status for regulation of the SVEP1. Since SVEP1 protein mediates
      cellular adhesion, this data might be beneficial for the future characterization
      of SVEP1 expression in the interactions existing in bone.

PMID- 21963385
TI  - Stochastic modulations of the pace and patterns of ageing: impacts on quasi
      stochastic distributions of multiple geriatric pathologies.
AB  - All phenotypes result from interactions between Nature, Nurture and Chance. The
      constitutional genome is clearly the dominant factor in explaining the striking
      differences in the pace and patterns of ageing among species. We are now in a
      position to reveal salient features underlying these differential modulations,
      which are likely to be dominated by regulatory domains. By contrast, I shall
      argue that stochastic events are the major players underlying the surprisingly
      large intra-specific variations in lifespan and healthspan. I shall review well
      established as well as more speculative categories of chance events--somatic
      mutations, protein synthesis error catastrophe and variegations of gene
      expression (epigenetic drift), with special emphasis upon the latter. I shall
      argue that stochastic drifts in variegated gene expression are the major
      contributors to intra-specific differences in the pace and patterns of ageing
      within members of the same species. They may be responsible for the quasi
      stochastic distributions of major types of geriatric pathologies, including the
      "big three" of Alzheimer's disease, atherosclerosis and, via the induction of
      hyperplasias, cancer. They may be responsible for altered stoichiometries of
      heteromultimeric mitochondrial complexes, potentially leading to such disorders
      as sarcopenia, nonischemic cardiomyopathy and Parkinson's disease.

PMID- 21963387
TI  - Rapid identification of clinical isolates of Bacteroides species by matrix
      assisted laser-desorption/ionization time-of-flight mass spectrometry.
AB  - The objective of this study was to compare MALDI-TOF MS and Rapid ID 32A with 16S
      rRNA gene sequencing, the reference method for identification of Bacteroides
      species. Results show that MALDI-TOF MS can be a good option for identification
      of Bacteroides species, especially if the database is expanded.

PMID- 21963388
TI  - Acute persistent traumatic anterior dislocation of the fractured radial head: a
      case report and surgical technique.

PMID- 21963389
TI  - The effect of probiotics on faecal microbiota and genotoxic activity of faecal
      water in patients with atopic dermatitis: a randomized, placebo-controlled study.
AB  - BACKGROUND: Colonic microbiota is involved in the etiology of colon cancer
      according to several reports. Studies also indicate that the microbiota differs
      between atopic patients and healthy subjects. OBJECTIVE: To evaluate whether a
      probiotic mix containing Lactobacillus paracasei Lpc-37, Lactobacillus
      acidophilus 74-2, and Bifidobacterium animalis subsp. lactis DGCC 420 can affect
      the microbiota and its genotoxic activity in healthy subjects and patients with
      atopic dermatitis (AD). METHODS: A placebo-controlled cross-over study was
      conducted. Fifteen healthy adults and 15 adult AD patients consumed 2*100 ml/d of
      either a probiotic or a placebo drink for 8 weeks followed by a wash out period
      of 2 weeks before crossing the intervention. Faecal water was isolated from stool
      samples collected at the end of each period. HT29c19a cells incubated with faecal
      water were measured for DNA damage using single-cell gel electrophoresis ("comet
      assay"). Bacterial species were determined by qPCR and concentrations of short
      chain fatty acids were measured by means of gas chromatography. RESULTS:
      Probiotic supplementation resulted in a significant increase in lactobacilli,
      whereas numbers of Bifidobacteria and Bacteroidetes remained unchanged.
      Clostridium perfringens cluster I-II was significantly reduced in healthy
      subjects. Genotoxic potential (expressed as tail intensity) of faecal water, was
      not affected. However, tail intensity decreased significantly in the probiotic
      period compared to placebo (23.5 vs. 16.7%) in AD patients. Although faecal
      concentrations of short-chain fatty acids were not affected, faecal pH was
      significantly reduced (7.0 vs. 6.6) in AD patients after probiotics. CONCLUSION:
      The results indicate that probiotics lower the genotoxic potential of faecal
      water in AD patients. The faecal C. perfringens cluster I-II levels remained
      unaffected suggesting either a change in their activity, or the fact that other
      bacterial species are responsible for the reduced genotoxic activity of faecal
      water.

PMID- 21963390
TI  - [Perforated pharyngoesophageal diverticulum as a cause of cervical infection with
      mediastinal extension].

PMID- 21963391
TI  - Electrochemical synthesis of gold nanostructure modified electrode and its
      development in electrochemical DNA biosensor.
AB  - In this article, gold nanostructure modified electrodes were achieved by a simple
      one-step electrodeposition method. The morphologies of modified electrodes could
      be easily controlled by changing the pH of HAuCl(4) solution. The novel
      nanoflower-like particles with the nanoplates as the building blocks could be
      interestingly obtained at pH 5.0. The gold nanoflower modified electrodes were
      then used for the fabrication of electrochemical DNA biosensor. The DNA biosensor
      fabrication process was characterized by cyclic voltammetry and electrochemical
      impedance spectroscopy with the use of ferricyanide as an electrochemical redox
      indicator. The DNA immobilization and hybridization on gold nanoflower modified
      electrode was studied with the use of [Ru(NH(3))(6)](3+) as a hybridization
      indicator. The electrochemical DNA biosensor shows a good selectivity and
      sensitivity toward the detection of target DNA. A detection limit of 1 pM toward
      target DNA could be obtained.

PMID- 21963392
TI  - Variation in melatonin receptors (Mel(1a) and Mel(1b)) and androgen receptor (AR)
      expression in the spleen of a seasonally breeding bird, Perdicula asiatica.
AB  - Daily variation in the peripheral level of melatonin plays a major role in
      integrating reproduction and environmental information for seasonally breeding
      birds. However, the variation in immunity and reproduction has never been
      assessed in any avian species on a 24 h time scale. Therefore, to understand the
      relationship between immune function and reproductive phases in a seasonally
      breeding bird, Perdicula asiatica, the Indian jungle bush quail, we studied the
      daily variation of melatonin and testosterone levels along with expression of
      their receptors Mel(1a), Mel(1b), and androgen receptor in the spleen during the
      reproductively active phase. Immunocytochemistry for the melatonin receptors
      Mel(1a) and Mel(1b) presented a differential distribution pattern. Western blot
      of splenic protein suggested a daily rhythm of melatonin receptors, while
      acrophases for the two melatonin receptors Mel(1a) and Mel(1b) differed by 4 h,
      suggesting that the expression of the receptors may peak at different times,
      causing more of either Mel(1a) or Mel(1b) to be available at a particular time to
      mediate function. The circulatory melatonin level correlated with percentage
      stimulation ratio of splenocytes and plasma interleukin-2 level, but did not
      correlate with testosterone or androgen receptor, suggesting that melatonin could
      be a major hormone imparting a time-of-day effect on the modulation of immune
      function in a seasonally breeding bird during the reproductively active phase.

PMID- 21963393
TI  - Maize rayado fino virus virus-like particles expressed in tobacco plants: A new
      platform for cysteine selective bioconjugation peptide display.
AB  - Maize rayado fino virus (MRFV) virus-like-particles (VLPs) produced in tobacco
      plants were examined for their ability to serve as a novel platform to which a
      variety of peptides can be covalently displayed when expressed through a Potato
      virus X (PVX)-based vector. To provide an anchor for chemical modifications,
      three Cys-MRFV-VLPs mutants were created by substituting several of the amino
      acids present on the shell of the wild-type MRFV-VLPs with cysteine residues. The
      mutant designated Cys 2-VLPs exhibited, under native conditions, cysteine thiol
      reactivity in bioconjugation reactions with a fluorescent dye. In addition, this
      Cys 2-VLPs was cross-linked by NHS-PEG4-Maleimide to 17 (F) and 8 (HN) amino acid
      long peptides, corresponding to neutralizing epitopes of Newcastle disease virus
      (NDV). The resulting Cys 2-VLPs-F and Cys 2-VLPs-HN were recognized in Western
      blots by antibodies to MRFV as well as to F and HN. The results demonstrated that
      plant-produced MRFV-VLPs have the ability to function as a novel platform for the
      multivalent display of surface ligands.

PMID- 21963394
TI  - Evaluation of electrospray differential mobility analysis for virus particle
      analysis: Potential applications for biomanufacturing.
AB  - The technique of electrospray differential mobility analysis (ES-DMA) was
      examined as a potential potency assay for routine virus particle analysis in
      biomanufacturing environments (e.g., evaluation of vaccines and gene delivery
      products for lot release) in the context of the International Committee of
      Harmonisation (ICH) Q2 guidelines. ES-DMA is a rapid particle sizing method
      capable of characterizing certain aspects of the structure (such as capsid
      proteins) and obtaining complete size distributions of viruses and virus-like
      particles. It was shown that ES-DMA can distinguish intact virus particles from
      degraded particles and measure the concentration of virus particles when
      calibrated with nanoparticles of known concentration. The technique has a
      measurement uncertainty of ~20%, is linear over nearly 3 orders of magnitude, and
      has a lower limit of detection of ~10(9)particles/mL. This quantitative assay was
      demonstrated for non-enveloped viruses. It is expected that ES-DMA will be a
      useful method for applications involving production and quality control of
      vaccines and gene therapy vectors for human use.

PMID- 21963395
TI  - Direct sequencing of hepatitis A virus and norovirus RT-PCR products from
      environmentally contaminated oyster using M13-tailed primers.
AB  - Human norovirus (HuNoV) and hepatitis A (HAV) are recognized as leading causes of
      non-bacterial foodborne associated illnesses in the United States. DNA sequencing
      is generally considered the standard for accurate viral genotyping in support of
      epidemiological investigations. Due to the genetic diversity of noroviruses
      (NoV), degenerate primer sets are often used in conventional reverse
      transcription (RT) PCR and real-time RT-quantitative PCR (RT-qPCR) for the
      detection of these viruses and cDNA fragments are generally cloned prior to
      sequencing. HAV detection methods that are sensitive and specific for real-time
      RT-qPCR yields small fragments sizes of 89-150bp, which can be difficult to
      sequence. In order to overcome these obstacles, norovirus and HAV primers were
      tailed with M13 forward and reverse primers. This modification increases the
      sequenced product size and allows for direct sequencing of the amplicons
      utilizing complementary M13 primers. HuNoV and HAV cDNA products from
      environmentally contaminated oysters were analyzed using this method. Alignments
      of the sequenced samples revealed >=95% nucleotide identities. Tailing NoV and
      HAV primers with M13 sequence increases the cDNA product size, offers an
      alternative to cloning, and allows for rapid, accurate and direct sequencing of
      cDNA products produced by conventional or real time RT-qPCR assays.

PMID- 21963396
TI  - The effect of cyclosporine A on the phosphorylation of the AMPK pathway in the
      rat hippocampus.
AB  - Cyclosporine A (CsA), an immunosuppressant and calcineurin inhibitor, induces
      hyperlipidemia in humans and animals. AMP-activated protein kinase (AMPK) is
      involved in metabolic homeostasis and lipid metabolism through modulating
      downstream molecules acetyl CoA carboxylase (ACC) and 3-hydroxy-3-methylglutaryl
      coenzyme A reductase (HMG-CoAR). AMPK activity is regulated by the
      phosphorylation at the Thr-172 residue by its upstream liver kinase B 1 (LKB1),
      Ca(2+)/calmodulin-dependent protein kinase kinase beta (CaMKKbeta) or
      transforming growth-factor-beta-activated kinase 1 (TAK1). AMPK can be
      deactivated through dephosphorylation by protein phosphatase 2Calpha (PP2Calpha).
      In this study, we demonstrated that phosphorylation at Thr-172-AMPK increased
      with a concurrent increase in the phosphorylation of Ser-431-LKB1 and Thr-184/187
      TAK1 in the rat hippocampus at 5 h after an intraperitoneal CsA (50 mg/kg)
      injection. CsA did not affect the phosphorylation of Thr-196-Ca(2+)/calmodulin
      dependent protein kinase 4 (CaMK4) and the amount of PP2Calpha. An increased
      phosphorylation of Ser-79-ACC and Ser-872-HMG-CoAR was also observed. In
      conclusion, our data indicate that CsA activates the AMPK pathway in the rat
      hippocampus, which suggests that CsA affects the regulatory signaling pathway of
      lipid metabolism in the rat brain.

PMID- 21963397
TI  - A case of acute stent thrombosis during treatment with the thrombopoietin
      receptor agonist peptide--romiplostim.
AB  - Romiplostim is a thrombopoietin receptor agonist that increases platelet counts
      and restores platelet function in patients with chronic immune thrombocytopenia
      (ITP). Increase in platelet count and platelet activation has been associated
      with increased thromboembolic risk. The present case report describes an
      interesting case of acute stent thrombosis in a patient with chronic immune
      thrombocytopenic purpura (ITP) being treated with romiplostim.

PMID- 21963398
TI  - Churg-Strauss syndrome presenting with acute myocarditis and cardiogenic shock.
AB  - Churg-Strauss syndrome (CSS) is a multisystem disorder characterised by asthma,
      prominent peripheral blood eosinophilia, and vasculitis signs. We report the case
      of a 22 year-old man admitted to the intensive care unit for acute myocarditis
      complicated with cardiogenic shock. Eosinophilia, history of asthma, lung
      infiltrates, paranasal sinusitis, glomerulonephritis, and abdominal pain
      suggested the diagnosis of CSS. Cardiac MRI confirmed cardiac involvement with a
      diffuse subendocardial delayed enhancement of the left ventricular wall, and a
      left ventricular ejection fraction (LVEF) of 30%. Acute myocarditis was confirmed
      with myocardial biopsy. The patient was successfully treated with systemic
      corticosteroids, intravenous cyclophosphamide, vasopressor inotropes, intra
      aortic balloon pump and mechanical ventilation, and was discharged 21 days later.
      One year after diagnosis, the patient was asymptomatic. The eosinophilic cell
      count was normal. Follow-up MRI at one year showed LVEF of 40% with persistent
      delayed enhancement. Cardiac involvement by CSS requires immediate therapy with
      corticosteroids and cyclophosphamide, which may allow recovery of the cardiac
      function.

PMID- 21963400
TI  - A new (semantic) reflexive brain-computer interface: in search for a suitable
      classifier.
AB  - The goal of the current study is to find a suitable classifier for
      electroencephalogram (EEG) data derived from a new learning paradigm which aims
      at communication in paralysis. A reflexive semantic classical (Pavlovian)
      conditioning paradigm is explored as an alternative to the operant learning
      paradigms, currently used in most brain-computer interfaces (BCIs). Comparable
      with a lie-detection experiment, subjects are presented with true and false
      statements. The EEG activity following true and false statements was classified
      with the aim to separate covert 'yes' from covert 'no' responses. Four
      classification algorithms are compared for classifying off-line data collected
      from a group of 14 healthy participants: (i) stepwise linear discriminant
      analysis (SWLDA), (ii) shrinkage linear discriminant analysis (SLDA), (iii)
      linear support vector machine (LIN-SVM) and (iv) radial basis function kernel
      support vector machine (RBF-SVM). The results indicate that all classifiers
      perform at chance level when separating conditioned 'yes' from conditioned 'no'
      responses. However, single conditioned reactions could be successfully classified
      on a single-trial basis (single conditioned reaction against a baseline
      interval). All of the four investigated classification methods achieve comparable
      performance, however results with RBF-SVM show the highest single-trial
      classification accuracy of 68.8%. The results suggest that the proposed paradigm
      may allow affirmative and negative (disapproving negative) communication in a BCI
      experiment.

PMID- 21963401
TI  - Partial stabilization-based guidance.
AB  - A novel nonlinear missile guidance law against maneuvering targets is designed
      based on the principles of partial stability. It is demonstrated that in a real
      approach which is adopted with actual situations, each state of the guidance
      system must have a special behavior and asymptotic stability or exponential
      stability of all states is not realistic. Thus, a new guidance law is developed
      based on the partial stability theorem in such a way that the behaviors of states
      in the closed-loop system are in conformity with a real guidance scenario that
      leads to collision. The performance of the proposed guidance law in terms of
      interception time and control effort is compared with the sliding mode guidance
      law by means of numerical simulations.

PMID- 21963399
TI  - Repeated antenatal corticosteroid treatments adversely affect neural transmission
      time and auditory thresholds in laboratory rats.
AB  - Antenatal corticosteroid (AC) treatment is given to pregnant women at risk for
      preterm birth to reduce infant morbidity and mortality by enhancing lung and
      brain maturation. However, there is no accepted regimen on how frequently AC
      treatments should be given and some studies found that repeated AC treatments can
      cause growth retardation and brain damage. Our goal was to assess the dose
      dependent effects of repeated AC treatment and estimate the critical number of AC
      courses to cause harmful effects on the auditory brainstem response (ABR), a
      sensitive measure of brain development, neural transmission and hearing loss. We
      hypothesized that repeated AC treatment would have harmful effects on the
      offspring's ABRs and growth only if more than 3 AC treatment courses were given.
      To test this hypothesis, pregnant Wistar rats were given either a high regimen of
      AC (HAC), a moderate regimen (MAC), a low regimen (LAC), or saline (SAL). An
      untreated control (CON) group was also used. Simulating the clinical condition,
      the HAC dams received 0.2mg/kg Betamethasone (IM) twice daily for 6 days during
      gestation days (GD) 17-22. The MAC dams received 3 days of AC treatment followed
      by 3 days of saline treatment on GD 17-19 and GD 20-22, respectively. The LAC
      dams received 1 day of AC treatment followed by 5 days of saline treatment on GD
      17 and GD 18-22, respectively. The SAL dams received 6 days of saline treatment
      from GD 17 to 22 (twice daily, isovolumetric to the HAC injections, IM). The
      offspring were ABR-tested on postnatal day 24. Results indicated that the ABR's
      P4 latencies (neural transmission time) were significantly prolonged (worse) in
      the HAC pups and that ABR's thresholds were significantly elevated (worse) in the
      HAC and MAC pups when compared to the CON pups. The HAC and MAC pups were also
      growth retarded and had higher postnatal mortality than the CON pups. The SAL and
      LAC pups showed little or no adverse effects. In conclusion, repeated AC
      treatment had harmful effects on the rat offspring's ABRs, postnatal growth and
      survival. The prolonged ABR latencies reflect slowed neural transmission times
      along the auditory nerve and brainstem auditory pathway. The elevated ABR
      thresholds reflect hearing deficits. We concluded that repeated AC treatment can
      have harmful neurological, sensory and developmental effects on the rat
      offspring. These effects should be considered when weighing the benefits and
      risks of repeated AC treatment and when monitoring and managing the prenatally
      exposed child for possible adverse effects.

PMID- 21963402
TI  - Lack of correlation between hypnotic susceptibility and various components of
      attention.
AB  - The purpose of our study was to measure the relationship between performance on
      various attentional tasks and hypnotic susceptibility. Healthy volunteers (N=116)
      participated in a study, where they had to perform several tasks measuring
      various attention components in a waking state: sustained attention, selective or
      focused attention, divided attention and executive attention in task switching.
      Hypnotic susceptibility was measured in a separate setting by the Waterloo
      Stanford Groups Scale of Hypnotic Susceptibility, Form C (WSGC). We found no
      significant correlation between any of the attentional measures and hypnotic
      susceptibility. Highly hypnotizables did not prove to be superior to or worse
      than the other individuals in any of the tests. These results do not support the
      neuropsychophysiological model of hypnosis, as they show no consistent
      relationship between hypnotic susceptibility and waking attentional performance.

PMID- 21963403
TI  - Prime and probability: causal knowledge affects inferential and predictive
      effects on self-agency experiences.
AB  - Experiences of having caused a certain outcome may arise from motor predictions
      based on action-outcome probabilities and causal inferences based on pre
      activated outcome representations. However, when and how both indicators combine
      to affect such self-agency experiences is still unclear. Based on previous
      research on prediction and inference effects on self-agency, we propose that
      their (combined) contribution crucially depends on whether people have knowledge
      about the causal relation between actions and outcomes that is relevant to
      subsequent self-agency experiences. Therefore, we manipulated causal knowledge
      that was either relevant or irrelevant by varying the probability of co
      occurrence (50% or 80%) of specific actions and outcomes. Afterwards, we measured
      self-agency experiences in an action-outcome task where outcomes were primed or
      not. Results showed that motor prediction only affected self-agency when relevant
      actions and outcomes were learned to be causally related. Interestingly, however,
      inference effects also occurred when no relevant causal knowledge was acquired.

PMID- 21963404
TI  - DNA repair inhibitors: where do we go from here?

PMID- 21963405
TI  - Differences in protein binding and cytokine release from monocytes on
      commercially sourced tissue culture polystyrene.
AB  - Tissue culture polystyrene (TCPS) is a ubiquitous substrate used by many
      researchers in the biomedical and biological sciences. Different parameters
      involved in the production of TCPS, including the treatment time and the use of
      reactive gases and chemical agents, can have a significant influence on the
      ultimate surface properties achieved. The assumption that they will all yield a
      consistent and controlled product has not proven to be true. To provide a better
      insight into the bioactivity differences in TCPS supplied by different
      manufacturers, TCPS from three different companies (Sarstedt, Wisent Corp., and
      Becton Dickinson (BD)) were analyzed for their surface properties, protein
      adsorption characteristics, and interactions with human monocytes. Marked
      differences were observed in terms of surface wettability and surface chemistry.
      Furthermore, Wisent TCPS adsorbed more than twice the amount of serum proteins
      compared with BD and Sarstedt TCPS. Sarstedt showed significantly more cell
      retention (more DNA) compared with both BD and Wisent TCPS brands over a 7 day
      culture period. Cytokine release from monocytes adherent on the three different
      TCPS also differed significantly, suggesting that the differences in the surface
      properties were sufficient to differentially mediate monocyte activation. These
      results have important implications for TCPS research use, in terms of
      appreciating the interpretation of the data when TCPS is used as a control
      substrate as well as when it is used where a pre-conditioned state would
      influence the outcome of the study.

PMID- 21963406
TI  - Protein adsorption on colloidal alumina particles functionalized with amino,
      carboxyl, sulfonate and phosphate groups.
AB  - Colloidal oxide particles in biomedical or biotechnological applications
      immediately become coated with proteins of the biological medium, a process which
      is strongly influenced by the surface characteristics of the particles.
      Fundamental correlations between surface characteristics and the, so far mainly
      uncontrollable, protein adsorption are still not clear. In this study the surface
      of colloidal alumina particles (d(50)=179 +/- 8 nm) was systematically adjusted
      with NH(2), COOH, SO(3)H and PO(3)H(2) functional groups to investigate the
      influence on the adsorption of the three model proteins, bovine serum albumin
      (BSA), lysozyme (LSZ) and trypsin (TRY). The surface functionalization is
      characterized and discussed in detail with regard to the morphology, isoelectric
      point, zeta potential, hydrophilic/hydrophobic properties, functional group
      density and stability. Protein-particle interaction was then assessed by
      evaluating the amount of protein adsorbed and the zeta potentials of protein
      particle conjugates. Protein adsorption was found to be influenced by the type of
      functional group as well as the expected electrostatic forces under the given
      experimental conditions. The level of protein adsorption might, hence, be
      specifically controlled by the type of surface functionalization. Possible
      adsorption modes of BSA, LSZ and TRY on the particles are suggested by
      considering the spatial surface potential distribution of the proteins calculated
      from the protein database file. The particles presented provide an excellent
      prerequisite for further investigation of fundamental particle-protein
      interactions and the design of functionally graded materials for biomedical and
      biotechnological applications, e.g. as drug carriers or for protein purification.

PMID- 21963407
TI  - Substitution of a single amino acid residue in the aromatic/arginine selectivity
      filter alters the transport profiles of tonoplast aquaporin homologs.
AB  - Aquaporins are integral membrane proteins that facilitate the transport of water
      and some small solutes across cellular membranes. X-ray crystallography of
      aquaporins indicates that four amino acids constitute an aromatic/arginine (ar/R)
      pore constriction known as the selectivity filter. On the basis of these four
      amino acids, tonoplast aquaporins called tonoplast intrinsic proteins (TIPs) are
      divided into three groups in Arabidopsis. Herein, we describe the
      characterization of two group I TIP1s (TgTIP1;1 and TgTIP1;2) from tulip (Tulipa
      gesneriana). TgTIP1;1 and TgTIP1;2 have a novel isoleucine in loop E (LE2
      position) of the ar/R filter; the residue at LE2 is a valine in all group I TIPs
      from model plants. The homologs showed mercury-sensitive water channel activity
      in a fast kinetics swelling assay upon heterologous expression in Pichia
      pastoris. Heterologous expression of both homologs promoted the growth of P.
      pastoris on ammonium or urea as sole sources of nitrogen and decreased growth and
      survival in the presence of H(2)O(2). TgTIP1;1- and TgTIP1;2-mediated H(2)O(2)
      conductance was demonstrated further by a fluorescence assay. Substitutions in
      the ar/R selectivity filter of TgTIP1;1 showed that mutants that mimicked the
      ar/R constriction of group I TIPs could conduct the same substrates that were
      transported by wild-type TgTIP1;1. In contrast, mutants that mimicked group II
      TIPs showed no evidence of urea or H(2)O(2) conductance. These results suggest
      that the amino acid residue at LE2 position is critical for the transport
      selectivity of the TIP homologs and group I TIPs might have a broader spectrum of
      substrate selectivity than group II TIPs.

PMID- 21963409
TI  - Probing the interaction of lipids with the non-annular binding sites of the
      potassium channel KcsA by magic-angle spinning NMR.
AB  - The activity of the potassium channel KcsA is tightly regulated through the
      interactions of anionic lipids with high-affinity non-annular lipid binding sites
      located at the interface between the channel's subunits. Here we present solid
      state phosphorous NMR studies that resolve the negatively charged lipid
      phosphatidylglycerol within the non-annular lipid-binding site. Perturbations in
      chemical shift observed upon the binding of phosphatidylglycerol are indicative
      of the interaction of positively charged sidechains within the non-annular
      binding site and the negatively charged lipid headgroup. Site directed
      mutagenesis studies have attributed these charge interactions to R64 and R89.
      Functionally the removal of the positive charges from R64 and R89 appears to act
      synergistically to reduce the probability of channel opening.

PMID- 21963410
TI  - Identification and functional characterization of zebrafish K(2P)10.1 (TREK2) two
      pore-domain K(+) channels.
AB  - Two-pore-domain potassium (K(2P)) channels mediate K(+) background currents that
      stabilize the resting membrane potential and contribute to repolarization of
      action potentials in excitable cells. The functional significance of K(2P)
      currents in cardiac electrophysiology remains poorly understood. Danio rerio
      (zebrafish) may be utilized to elucidate the role of cardiac K(2P) channels in
      vivo. The aim of this work was to identify and functionally characterize a
      zebrafish otholog of the human K(2P)10.1 channel. K(2P)10.1 orthologs in the D.
      rerio genome were identified by database analysis, and the full zK(2P)10.1 coding
      sequence was amplified from zebrafish cDNA. Human and zebrafish K(2P)10.1
      proteins share 61% identity. High degrees of conservation were observed in
      protein domains relevant for structural integrity and regulation. K(2P)10.1
      channels were heterologously expressed in Xenopus oocytes, and currents were
      recorded using two-electrode voltage clamp electrophysiology. Human and zebrafish
      channels mediated K(+) selective background currents leading to membrane
      hyperpolarization. Arachidonic acid, an activator of hK(2P)10.1, induced robust
      activation of zK(2P)10.1. Activity of both channels was reduced by protein kinase
      C. Similar to its human counterpart, zK(2P)10.1 was inhibited by the
      antiarrhythmic drug amiodarone. In summary, zebrafish harbor K(2P)10.1 two-pore
      domain K(+) channels that exhibit structural and functional properties largely
      similar to human K(2P)10.1. We conclude that the zebrafish represents a valid
      model to study K(2P)10.1 function in vivo.

PMID- 21963411
TI  - RFID system for newborn identity reconfirmation in hospital: exposure assessment
      of a realistic newborn model and effects of the change of the dielectric
      properties with age.
AB  - This paper addresses the exposure assessment of RFID devices for newborn identity
      reconfirmation. To that purpose, a realistic newborn model ("Baby") is used to
      evaluate by a computational approach the levels of exposure due to these devices.
      Considering the average technical specifications currently in use, the exposure
      matrix in Baby shows that the systems comply with the ICNIRP exposure guidelines.
      As second aim, the effects of the change of the tissue dielectric properties with
      age on the so called "exposure matrix" (set of induced magnetic and electric
      field together with the derived values of SAR) is addressed. Specifically, three
      different approaches proposed in literature for the age variation of the
      dielectric properties at 13.56 MHz (the working frequency of the RFID systems for
      these applications) have been implemented using the Baby geometrical model. The
      related exposure matrices were then compared with the results obtained using the
      adult properties. No clear trend can be identified on the exposure matrices
      obtained varying the dielectric properties at 13.56 MHz, although the results
      could suggest a trend toward the underestimation of the exposure using adult
      properties.

PMID- 21963412
TI  - Rapporteur's report on Session 2: Epidemiological findings.

PMID- 21963413
TI  - Rapporteur's report on Session 4--exposure and dosimetry.

PMID- 21963408
TI  - Gap junctions and hemichannels in signal transmission, function and development
      of bone.
AB  - Gap junctional intercellular communication (GJIC) mediated by connexins, in
      particular connexin 43 (Cx43), plays important roles in regulating signal
      transmission among different bone cells and thereby regulates development,
      differentiation, modeling and remodeling of the bone. GJIC regulates osteoblast
      formation, differentiation, survival and apoptosis. Osteoclast formation and
      resorptive ability are also reported to be modulated by GJIC. Furthermore,
      osteocytes utilize GJIC to coordinate bone remodeling in response to anabolic
      factors and mechanical loading. Apart from gap junctions, connexins also form
      hemichannels, which are localized on the cell surface and function independently
      of the gap junction channels. Both these channels mediate the transfer of
      molecules smaller than 1.2kDa including small ions, metabolites, ATP,
      prostaglandin and IP(3). The biological importance of the communication mediated
      by connexin-forming channels in bone development is revealed by the low bone mass
      and osteoblast dysfunction in the Cx43-null mice and the skeletal malformations
      observed in occulodentodigital dysplasia (ODDD) caused by mutations in the Cx43
      gene. The current review summarizes the role of gap junctions and hemichannels in
      regulating signaling, function and development of bone cells. This article is
      part of a Special Issue entitled: The Communicating junctions, composition,
      structure and characteristics.

PMID- 21963414
TI  - Analyses related to the development of DSM-5 criteria for substance use related
      disorders: 1. Toward amphetamine, cocaine and prescription drug use disorder
      continua using Item Response Theory.
AB  - BACKGROUND: Prior research has demonstrated the dimensionality of alcohol,
      nicotine and cannabis use disorders criteria. The purpose of this study was to
      examine the unidimensionality of DSM-IV cocaine, amphetamine and prescription
      drug abuse and dependence criteria and to determine the impact of elimination of
      the legal problems criterion on the information value of the aggregate criteria.
      METHODS: Factor analyses and Item Response Theory (IRT) analyses were used to
      explore the unidimensionality and psychometric properties of the illicit drug use
      criteria using a large representative sample of the U.S. population. RESULTS: All
      illicit drug abuse and dependence criteria formed unidimensional latent traits.
      For amphetamines, cocaine, sedatives, tranquilizers and opioids, IRT models fit
      better for models without legal problems criterion than models with legal
      problems criterion and there were no differences in the information value of the
      IRT models with and without the legal problems criterion, supporting the
      elimination of that criterion. CONCLUSION: Consistent with findings for alcohol,
      nicotine and cannabis, amphetamine, cocaine, sedative, tranquilizer and opioid
      abuse and dependence criteria reflect underlying unitary dimensions of severity.
      The legal problems criterion associated with each of these substance use
      disorders can be eliminated with no loss in informational value and an advantage
      of parsimony. Taken together, these findings support the changes to substance use
      disorder diagnoses recommended by the American Psychiatric Association's DSM-5
      Substance and Related Disorders Workgroup.

PMID- 21963415
TI  - Profiles of motor and cognitive impairment in the transgenic rat model of
      Huntington's disease.
AB  - The transgenic Huntington's disease (tgHD) rat strain provides a well regarded
      transgenic animal model of Huntington's disease, offering the prospect for a more
      detailed functional analysis in rats, along with neurological and therapeutic
      interventions, than is possible in the more widely available mouse models. In the
      present experiments, we compare the performance of heterozygous and homozygous
      tgHD rats against wildtype littermates on a range of motor and cognitive
      assessments in five separate cohorts of rats between 8 and 22 months of age. Male
      but not female heterozygous tgHD rats exhibit modest motor deficits in rotarod
      and staircase reaching tests, whereas most cognitive tests (including object
      recognition, exploration of novelty, delayed alternation, choice reaction time,
      and serial implicit learning tasks) revealed at best small or inconsistent
      deficits, in homozygous as well as heterozygous animals, up to 22 months of age.
      Thus, although we have observed modest but clear-cut deficits in motor phenotype,
      with a sex difference in line with previous reports, we have not established a
      robust cognitive impairment in this strain on a range of tasks sensitive to
      frontostriatal function, as required for testing novel (symptomatic, protective
      or reparative) therapeutics in a robust, valid, animal model of human
      Huntington's disease.

PMID- 21963416
TI  - Pandemic A/H1N1/2009 influenza virus in swine, Cameroon, 2010.
AB  - Although swine origin A/H1N1/2009 influenza virus (hereafter "pH1N1") has been
      detected in swine in 20 countries, there has been no published surveillance of
      the virus in African livestock. The objective of this study was to assess the
      circulation of influenza A viruses, including pH1N1 in swine in Cameroon, Central
      Africa. We collected 108 nasal swabs and 98 sera samples from domestic pigs
      randomly sampled at 11 herds in villages and farms in Cameroon. pH1N1 was
      isolated from two swine sampled in northern Cameroon in January 2010. Sera from
      28% of these herds were positive for influenza A by competitive ELISA and 92.6%
      of these swine showed cross reactivity with pandemic A/H1N1/2009 influenza virus
      isolated from humans. These results provide the first evidence of this virus in
      the animal population in Africa. In light of the significant role of swine in the
      ecology of influenza viruses, our results call for greater monitoring and study
      in Central Africa.

PMID- 21963417
TI  - Antimicrobial activity of gallium maltolate against Staphylococcus aureus and
      methicillin-resistant S. aureus and Staphylococcus pseudintermedius: An in vitro
      study.
AB  - Gallium is a trivalent semi-metallic element that has shown antimicrobial
      activity against several important human pathogens. This antimicrobial activity
      is likely related to its substitution in important iron-dependent pathways of
      bacteria. The genus Staphylococcus, which includes human and animal pathogens
      that cause significant morbidity and mortality, requires iron for growth and
      colonization. In this study, gallium maltolate, at various concentrations between
      50 and 200MUM, inhibited the in vitro growth of Staphylococcus aureus and
      methicillin-resistant S. aureus (MRSA) at time-points between 8 and 36h after
      inoculation. The inhibitory activity of gallium maltolate against clinical
      isolates of MRSA and methicillin-resistant Staphylococcus pseudintermedius (MRSP)
      from a veterinary teaching hospital was determined.

PMID- 21963418
TI  - The complex interplay between stress and bacterial infections in animals.
AB  - Over the past decade, an increasing awareness has arisen of the role of
      neuroendocrine hormones in the susceptibility of mammalian hosts to a bacterial
      infection. During a stress response, glucocorticoids, catecholamines and
      neuroendocrine factors are released into the circulation of the host. For a long
      time the effects of stress on the course of an infection have been exclusively
      ascribed to the direct effect of stress-related hormones on the immune system and
      the intestinal barrier function. Chronic stress is known to cause a shift from T
      helper 1-mediated cellular immunity toward T helper 2-mediated humoral immunity,
      which can influence the course of an infection and/or the susceptibility to a
      microorganism. Bacteria can however also respond directly to stress-related host
      signals. Catecholamines can alter growth, motility, biofilm formation and/or
      virulence of pathogens and commensal bacteria, and as a consequence influence the
      outcome of infections by these bacteria in many hosts. For some bacteria, such as
      Salmonella, Escherichia coli and Pseudomonas aeruginosa it was shown that this
      influence is regulated by quorum sensing mechanisms. In this manuscript an
      overview of how and when stress influences the outcome of bacterial infections in
      animals is provided.

PMID- 21963419
TI  - Quantification of transmission of livestock-associated methicillin resistant
      Staphylococcus aureus in pigs.
AB  - Antimicrobial resistance in pigs becomes a public health issue when resistant
      organisms transfer from pigs to humans. Pigs are a large reservoir for livestock
      associated (LA-)MRSA and people in contact with pigs are at risk for infection
      with LA-MRSA. Transmission and persistence of LA-MRSA within a pig population
      contributes to the maintenance of this zoonotic reservoir. Current knowledge on
      colonization and transmission of LA-MRSA in pigs is limited and mainly based on
      observational field surveys. Two experiments were performed to colonize pigs and
      quantify transmission of LA-MRSA between pigs. In the first experiment,
      colonization of six-week old piglets failed after intranasal inoculation,
      confirming the complexity of MRSA-colonization. In the second experiment, naive
      pigs got colonized after exposure to orally inoculated pigs. Subsequently, these
      contact-infected pigs transmitted MRSA to a new group of naive pigs. The
      reproduction ratio, R(0), was estimated with a SIS-model to quantify transmission
      between the first and second contact pigs as this resembles more the natural
      transmission. Two scenarios were evaluated, with different assumptions regarding
      infection status of individual pigs. R(0) varied between 3.7 and 4.3 and was
      significantly above 1, indicating a high probability of persistence of LA-MRSA,
      even without antimicrobial use.

PMID- 21963420
TI  - The effect of auto-vaccination therapy on the phenotypic variation of one clonal
      type of Staphylococcus aureus isolated from cows with mastitis.
AB  - The aim of this study was to demonstrate the effect of auto-vaccine therapy on
      selected properties of Staphylococcus aureus strains, isolated from milk of cows
      with subclinical mastitis. The experiment was based on auto-vaccines which were
      prepared from S. aureus strains isolated from 16 cows. S. aureus strains isolated
      from cows on the 7th, 21st and 35th day following auto-vaccination, were analyzed
      phenotypically and genotypically. The isolated strains represented 17 biotypes
      all belonging to one clonal type. Increases of new biotypes of S. aureus were
      detected on the 35th day of therapy. Among 48 re-isolated strains, 18.75% (9/48)
      revealed single and 12.50% (6/48) multiple phenotypical changes. The present
      study demonstrated that during auto-vaccine therapy, S. aureus strains can change
      phenotypically, pointing out the necessity for using precise diagnostic methods,
      that would make possible a better assessment of the used therapy.

PMID- 21963421
TI  - Selection of effective features for ECG beat recognition based on nonlinear
      correlations.
AB  - OBJECTIVE: The objective of this study is to develop feature selectors based on
      nonlinear correlations in order to select the most effective and least redundant
      features from an ECG beat classification system based on higher order statistics
      of subband components and a feed-forward back-propagation neural network, denoted
      as HOS-DWT-FFBNN. METHODS AND MATERIALS: Three correlation-based filters (NCBFs)
      are proposed. Two of them, NCBF1 and NCBF2, apply feature-feature correlation to
      remove redundant features prior to the feature selection process based on feature
      class correlation. The other, SUFCO, skips the redundancy reduction process and
      selects features based only on feature-class correlation. The performance of
      these filters is compared to another commonly used nonlinear feature selection
      method, Relief-F. The discriminality and redundancy of the retained features are
      evaluated quantitatively. The performance of the most effective NCBF is compared
      with that of the linear correlation-based filter (LCBF) and other representative
      heartbeat classifiers in the literature. RESULTS: The results demonstrate that
      the two NCBFs based on both feature-feature and feature-class correlation
      methods, i.e. NCBF1 and NCBF2, outperform the other two methods, i.e. SUFCO and
      Relief-F. An accuracy of as high as 96.34% can be attained with as few as eight
      features. When tested with statistical methods, the retained features selected by
      the NCBF1/NCBF2 approach are demonstrated to be more discriminative and less
      redundant when compared with those features selected by other methods. When
      compared with LCBF and other heartbeat classifiers in the literature, the
      proposed NCBF1/NCBF2 approach in conjunction with the HOS-DWT-FFBNN structure
      outperform them with improved performance that allows discrimination of more beat
      types and fewer feature dimensions. CONCLUSION: This study demonstrates the
      effectiveness and superiority of the proposed approach for ECG beat recognition.

PMID- 21963422
TI  - Differential effects of escitalopram challenge on disgust processing in obsessive
      compulsive disorder.
AB  - INTRODUCTION: Literature on the ability of patients with obsessive-compulsive
      disorder (OCD) to recognize static facial expressions of disgust is not
      consistent. We aimed to investigate whether OCD is associated with deficits in
      the recognition of disgust in a dynamic task, and if so, whether the acute
      administration of the selective serotonin reuptake inhibitor (SSRI) escitalopram
      would result in the normalization of such deficits. METHODS: OCD patients (n=20)
      and matched healthy controls (n=20) received a single dose of escitalopram 20mg
      on one day, and a single dose of placebo on another day, in randomized order,
      under double-blind conditions. Accuracy (i.e. the percentage of correct answers)
      and sensitivity to disgust stimuli (defined as the lowest level of emotional
      intensity expressed on the photo image after which no errors were made in the
      recognition of disgust for subsequent trials of increasing intensity) were
      compared in OCD patients and controls, with a repeated measures analysis of
      variance using a mixed model approach. RESULTS: On placebo, the accuracy of, and
      sensitivity to, disgust stimuli were similar across groups. OCD patients had more
      accurate and more sensitive recognition of disgust after acute SSRI
      administration than after placebo, while controls had less accurate recognition
      and less sensitive recognition of disgust after acute SSRI administration than
      after placebo. CONCLUSIONS: The use of a dynamic facial recognition task
      demonstrated altered responses to disgust in OCD patients compared to healthy
      controls after a pharmacological challenge with escitalopram. These findings
      suggest that the serotonergic system plays a role in disgust recognition.

PMID- 21963423
TI  - Activity of bone morphogenetic protein-7 after treatment at various temperatures:
      freezing vs. pasteurization vs. allograft.
AB  - Insufficient bone union is the occasional complication of biomechanical
      reconstruction after malignant bone tumor resection using temperature treated
      tumor bearing bone; freezing, pasteurization, and autoclaving. Since bone
      morphogenetic protein (BMP) plays an important role in bone formation, we
      assessed the amount and activity of BMP preserved after several temperature
      treatments, including -196 and -73 degrees C for 20 min, 60 and 100 degrees C for
      30 min, 60 degrees C for 10h following -80 degrees C for 12h as an allograft
      model, and 4 degrees C as the control. The material extracted from the human
      femoral bone was treated, and the amount of BMP-7 was analyzed using an enzyme
      linked immunosorbent assay. Then, the activity of recombinant human BMP-7 after
      the treatment was assessed using a bioassay with NIH3T3 cells and immunoblotting
      analysis to measure the amount of phospho-Smad, one of the signaling substrates
      that reflect the intracellular reaction of BMPs. Both experiments revealed that
      BMP-7 was significantly better preserved in the hypothermia groups. The
      percentages of the amount of BMP-7 in which the control group was set at 100%
      were 114%, 108%, 70%, 49%, and 53% in the -196, -73, 60, 100 degrees C, and the
      allograft-model group, respectively. The percentages of the amount of phospho
      Smad were 89%, 87%, 24%, 4.9%, and 14% in the -196, -73, 60, 100 degrees C, and
      the allograft-model group, respectively. These results suggested that freezing
      possibly preserves osteoinductive ability than hyperthermia treatment.

PMID- 21963424
TI  - Hemorrhage in the endolymphatic sac: a cause of hearing fluctuation in enlarged
      vestibular aqueduct.
AB  - OBJECTIVE: Most of the patients with enlarged vestibular aqueduct (EVA)
      experience sudden hearing deterioration, but the exact mechanism is unclear. We
      analyzed magnetic resonance (MR) images and the cellular components of endolymph
      obtained from the endolymphatic sac in patients with EVA, in order to demonstrate
      the cause of sudden hearing loss. METHODS: A total of 25 patients (50 ears) with
      EVA, who had severe to profound hearing loss, were included in this retrospective
      clinical study. MR examinations were performed by a 3.0-T MR system using an 8
      channel sensitivity-encoding head coil. We analyzed endolymphatic fluid harvested
      from the endolymphatic sac during cochlear implantations in four patients.
      RESULTS: The area of low signal intensity in the endolymphatic sac was observed
      on T2-weighted MR images for 15 of 50 ears. This area was observed more
      frequently in patients who experienced recent sudden hearing loss (10/12, 83%)
      than those with stable hearing (5/38, 13%)(Fisher's exact test, p<0.001). In
      addition, this area showed high signal intensity on fluid attenuated inversion
      recovery images. Cytologic analysis of the aspirated endolymph from the
      endolymphatic sac in the patients with this area revealed many erythrocytes.
      CONCLUSION: Our data suggests that hemorrhage in the endolymphatic sac could be a
      cause of sudden hearing deterioration in patients with EVA.

PMID- 21963425
TI  - Nephron formation adopts a novel spatial topology at cessation of nephrogenesis.
AB  - Nephron number in the mammalian kidney is known to vary dramatically, with
      postnatal renal function directly influenced by nephron complement. What
      determines final nephron number is poorly understood but nephron formation in the
      mouse kidney ceases within the first few days after birth, presumably due to the
      loss of all remaining nephron progenitors via epithelial differentiation. What
      initiates this event is not known. Indeed, whether nephron formation occurs in
      the same way at this time as during embryonic development has also not been
      examined. In this study, we investigate the key cellular compartments involved in
      nephron formation; the ureteric tip, cap mesenchyme and early nephrons; from
      postnatal day (P) 0 to 6 in the mouse. High resolution analyses of gene and
      protein expression indicate that loss of nephron progenitors precedes loss of
      ureteric tip identity, but show spatial shifts in the expression of cap
      mesenchyme genes during this time. In addition, cap mesenchymal volume and rate
      of proliferation decline prior to birth. Section-based 3D modeling and Optical
      Projection Tomography revealed a burst of ectopic nephron induction, with the
      formation of multiple (up to 5) nephrons per ureteric tip evident from P2. While
      the distal-proximal patterning of these nephrons occurred normally, their spatial
      relationship with the ureteric compartment was altered. We propose that this
      phase of nephron formation represents an acceleration of differentiation within
      the cap mesenchyme due to a displacement of signals within the nephrogenic niche.

PMID- 21963427
TI  - Effects of prepregnancy body mass index and weight gain during pregnancy on
      perinatal outcome in glucose-tolerant women.
AB  - AIM: The aim of this study was to determine the effects of maternal prepregnancy
      body mass index (BMI) and weight gain during pregnancy on perinatal outcome in
      non-diabetic women. METHODS: The clinical records of consecutive women who had
      undergone a glucose challenge test (GCT) and then delivered in our university
      hospital between January 2004 and December 2009 were retrospectively reviewed.
      Prepregnancy BMI and pregnancy weight gain were classified according to the US
      Institute of Medicine guidelines (1990). RESULTS: Of the eligible 2225 patients,
      obese and overweight women had a greater percentage of macrosomic babies (17.7%
      and 8.9%, respectively) compared with normal weight women (4.5%). However, when
      considered according to weight gain during pregnancy, the results were
      statistically significant only for excess weight gain in the obese (OR: 8.3, 95%
      CI: 2.4-28.4) and overweight (OR: 2.9, 95% CI: 1.2-6.8) groups. Also, the
      surgical delivery rate was significantly higher in the obese vs normal weight
      women (56% vs 36%, respectively) although, in this case, there was no difference
      according to normal and excess weight gain during pregnancy (OR: 1.4, 95% CI: 0.7
      2.6). CONCLUSION: Overweight and obese women have an increased risk rate of
      macrosomia that can be limited by well-controlled weight gain during pregnancy.
      There was also a significantly higher rate of surgical delivery in the obese
      compared with the normal weight group that was, however, independent of excessive
      weight gain during pregnancy.

PMID- 21963426
TI  - Tfap2a and Foxd3 regulate early steps in the development of the neural crest
      progenitor population.
AB  - The neural crest is a stem cell-like population exclusive to vertebrates that
      gives rise to many different cell types including chondrocytes, neurons and
      melanocytes. Arising from the neural plate border at the intersection of Wnt and
      Bmp signaling pathways, the complexity of neural crest gene regulatory networks
      has made the earliest steps of induction difficult to elucidate. Here, we report
      that tfap2a and foxd3 participate in neural crest induction and are necessary and
      sufficient for this process to proceed. Double mutant tfap2a (mont blanc, mob)
      and foxd3 (mother superior, mos) mob;mos zebrafish embryos completely lack all
      neural crest-derived tissues. Moreover, tfap2a and foxd3 are expressed during
      gastrulation prior to neural crest induction in distinct, complementary, domains;
      tfap2a is expressed in the ventral non-neural ectoderm and foxd3 in the dorsal
      mesendoderm and ectoderm. We further show that Bmp signaling is expanded in
      mob;mos embryos while expression of dkk1, a Wnt signaling inhibitor, is increased
      and canonical Wnt targets are suppressed. These changes in Bmp and Wnt signaling
      result in specific perturbations of neural crest induction rather than general
      defects in neural plate border or dorso-ventral patterning. foxd3 overexpression,
      on the other hand, enhances the ability of tfap2a to ectopically induce neural
      crest around the neural plate, overriding the normal neural plate border limit of
      the early neural crest territory. Although loss of either Tfap2a or Foxd3 alters
      Bmp and Wnt signaling patterns, only their combined inactivation sufficiently
      alters these signaling gradients to abort neural crest induction. Collectively,
      our results indicate that tfap2a and foxd3, in addition to their respective roles
      in the differentiation of neural crest derivatives, also jointly maintain the
      balance of Bmp and Wnt signaling in order to delineate the neural crest induction
      domain.

PMID- 21963428
TI  - Allosteric interactions between the oxytocin receptor and the beta2-adrenergic
      receptor in the modulation of ERK1/2 activation are mediated by
      heterodimerization.
AB  - The oxytocin receptor (OTR) and the beta(2)-adrenergic receptor (beta(2)AR) are
      key regulators of uterine contraction. These two receptors are targets of
      tocolytic agents used to inhibit pre-term labor. Our recent study on the nature
      of OTR- and beta(2)AR-mediated ERK1/2 activation in human hTERT-C3 myometrial
      cells suggested the presence of an OTR/beta(2)AR hetero-oligomeric complex (see
      companion article). The goal of this study was to investigate potential
      allosteric interactions between OTR and beta(2)AR and establish the nature of the
      interactions between these receptors in myometrial cells. We found that OTR
      mediated ERK1/2 activation was attenuated significantly when cells were
      pretreated with the beta(2)AR agonist isoproterenol or two antagonists,
      propranolol or timolol. In contrast, pretreatment of cells with a third beta(2)AR
      antagonist, atenolol resulted in an increase in OTR-mediated ERK1/2 activation.
      Similarly, beta(2)AR-mediated ERK1/2 activation was strongly attenuated by
      pretreatment with the OTR antagonists, atosiban and OTA. Physical interactions
      between OTR and beta(2)AR were demonstrated using co-immunoprecipitation,
      bioluminescence resonance energy transfer (BRET) and protein-fragment
      complementation (PCA) assays in HEK 293 cells, the latter experiments indicating
      the interactions between the two receptors were direct. Our analyses suggest
      physical interactions between OTR and beta(2)AR in the context of a new
      heterodimer pair lie at the heart of the allosteric effects.

PMID- 21963430
TI  - Morphological and biochemical analyses of original and regenerated lizard tails
      reveal variation in protein and lipid composition.
AB  - Caudal autotomy, or voluntary self-amputation of the tail, is a common and
      effective predator evasion mechanism used by most lizard species. The tail
      contributes to a multitude of biological functions such as locomotion,
      energetics, and social interactions, and thus there are often costs associated
      with autotomy. Notably, relatively little is known regarding bioenergetic costs
      of caudal autotomy in lizards, though key morphological differences exist between
      the original and regenerated tail that could alter the biochemistry and
      energetics. Therefore, we investigated lizard caudal biochemical content before
      and after regeneration in three gecko and one skink species. Specifically, we
      integrated biochemical and morphological analyses to quantify protein and lipid
      content in original and regenerated tails. All lizards lost significant body
      mass, mostly protein, due to autotomy and biochemical results indicated that
      original tails of all species contained a greater proportion of protein than
      lipid. Morphological analyses of two gecko species revealed interspecific
      differences in protein and lipid content of regenerated lizard tails. Results of
      this study contribute to our understanding of the biochemical consequences of a
      widespread predator evasion mechanism.

PMID- 21963429
TI  - Angiotensin II mediates cell survival through upregulation and activation of the
      serum and glucocorticoid inducible kinase 1.
AB  - The serum- and glucocorticoid-inducible kinase 1 (SGK1) is known to regulate a
      wide variety of cellular processes, including renal sodium retention and cell
      survival. Angiotensin II (Ang II) is one of the many signaling molecules capable
      of regulating SGK1 expression, and is also known to impact cell survival. Here,
      we examined the role of SGK1 in Ang II-mediated cell survival. We hypothesized
      that Ang II protects cells from apoptosis by upregulating and activating SGK1. To
      test this, we examined the effects of Ang II stimulation on SGK1 expression and
      downstream signaling. We also examined the effects of Ang II treatment and siRNA
      mediated SGK1 knockdown on apoptosis after serum starvation. We found that after
      2h of Ang II treatment, SGK1 mRNA expression was increased approximately 2-fold.
      This induction was sensitive to reductions in intracellular calcium levels after
      pretreatment with BAPTA-AM, but insensitive to the L-type calcium channel blocker
      verapamil. SGK1 induction was also sensitive to the tyrosine kinase inhibitor
      genistein. Ang II treatment also caused a rapid increase in the level of
      phosphorylation of SGK1 at Ser422 and Thr256, and Ser422 phosphorylation was
      rapamycin-sensitive. We found that Ang II treatment was protective against serum
      starvation-induced apoptosis, and this protective effect was significantly
      blunted when SGK1 was silenced via siRNA. Lastly, Ang II induced FOXO3A
      phosphorylation in an SGK1-dependent manner, thereby reducing the pro-apoptotic
      actions of FOXO3A. Overall, these results indicate that Ang II upregulates and
      activates SGK1, leading to increased cell survival via multiple, non-redundant
      mechanisms.

PMID- 21963431
TI  - A combination of the cytokinesis-block micronucleus cytome assay and centromeric
      identification for evaluation of the genotoxicity of dicamba.
AB  - The purpose of this study was to further investigate the cytotoxic and genotoxic
      effects of dicamba and Banvel((r)) employing the cytokinesis-block micronucleus
      cytome (CBMN-cyt) assay estimated by the analysis of the nuclear division index
      (NDI), the frequency of micronucleus (MN), nucleoplasmic bridges (NPBs), and
      nuclear buds (NBUDs). Besides, for mechanism of MN induction CREST anti
      kinetochore antibody analysis was performed. The activities of both compounds
      were tested within the range of 50-500 MUg/ml on Chinese hamster ovary (CHO-K1)
      cells. Overall, dicamba and Banvel((r)) produced a NDI dose-dependent decrease
      but the response was statistically significant only in cultures treated with
      Banvel((r)) at a 100-500 MUg/ml concentration range. A dose-dependent induction
      of MN was observed after dicamba- and Banvel((r))-treatments within the 50-400
      MUg/ml and 50-500 MUg/ml concentration-ranges, respectively. Induction of NPBs
      and NBUDs was significantly enhanced by both test compounds. The NPBs/MN ratio
      values found for dicamba and Banvel((r)) were 0.04-0.11 and 0.05-0.18,
      respectively. Results clearly demonstrated that dicamba and Banvel((r)) exerted
      both cyto- and genotoxic damage on CHO-K1 cells. Furthermore, the CBMN-cyt assay
      employed confirmed our previous investigations concerning the cellular and DNA
      damaging capabilities of dicamba and highlights that both clastogenic and
      aneugenic mechanisms are implicated in the MN induction.

PMID- 21963432
TI  - Comparative protein profile of human hepatoma HepG2 cells treated with graphene
      and single-walled carbon nanotubes: an iTRAQ-coupled 2D LC-MS/MS proteome
      analysis.
AB  - Graphitic nanomaterials are promising candidates for applications in electronics,
      energy, materials and biomedical areas. Nevertheless, few detailed studies
      related to the mechanistic understanding of these nanomaterials with the living
      systems have been performed to date. In the present study, our group applied the
      iTRAQ-coupled 2D LC-MS/MS approach to analyze the protein profile change of human
      hepatoma HepG2 cells treated with graphene and single-walled carbon nanotubes
      (SWCNTs), with the purpose of characterizing the interactions between living
      system and these nanomaterials at molecular level. Overall 37 differentially
      expressed proteins involved in metabolic pathway, redox regulation, cytoskeleton
      formation and cell growth were identified. Based on the protein profile, we found
      SWCNTs severely interfered the intracellular metabolic routes, protein synthesis
      and cytoskeletal systems. Moreover, our data suggested that SWCNTs might induce
      oxidative stress, thereby activating p53-mediated DNA damage checkpoint signals
      and leading to apoptosis. However, only moderate variation of protein levels for
      the cells treated with graphene was observed, which indicated graphene was less
      toxic and might be promising candidate for biomedical applications. We envision
      that this systematic characterization of cellular response at protein expression
      level will be of great importance to evaluate biocompatibility of nanomaterials.

PMID- 21963433
TI  - Host defense peptides in skin secretions of Odorrana tiannanensis: Proof for
      other survival strategy of the frog than merely anti-microbial.
AB  - Genus Odorrana, among all amphibians studied, is generally reported to have the
      most abundant and diversified anti-microbial peptides even from a single
      individual frog. In our previous work, 46 cDNA sequences encoding precursors of
      22 different anti-microbial peptides (AMPs) were characterized from the skin of
      frog, Odorrana tiannanensis. In this work, we reported the purification of three
      AMPs from skin secretions of O. tiannanensis. Their amino acid sequences matched
      well with the sequences deduced from cDNAs and they were designated as Odorranain
      C7HSa, Brevinin-1-OT2 and Odorranain-G-OT, respectively. Furthermore, we selected
      to analyze the four most structurally diversified sequences among the 22 AMPs
      that are significantly different from all reported AMPs. By structural
      characterization, three of them were designated as pleurain-E-OT, odorranain-G
      OT, odorranain-A-OT, belonging to AMP families already identified. The forth one
      with a unique 14-mer sequence of AILTTLANWARKFLa and C-terminal amidation
      represents the prototypes of a new class of amphibian AMP, and thereby named
      tiannanensin. Such broad diversity in sequences and structures are consistent
      with other species in Genus Odorrana. Multi-functions of the synthesized four
      special AMPs were screened, including anti-microbial, antioxidant, cytotoxic and
      hemolytic activities. The results suggest that these AMPs may employ
      sophisticated mechanisms of action in host defense in addition to anti-microbial,
      although their precise contribution to host defense still seems unclear.

PMID- 21963434
TI  - alpha-Crystallin protects human arginosuccinate lyase activity under freeze-thaw
      conditions.
AB  - Argininosuccinate lyase (ASL) catalyzes the conversion of argininosuccinate into
      arginine and fumarate, a key step in the biosynthesis of urea and arginine. ASL
      is a tetrameric enzyme but it dissociates into inactive dimers under low
      temperature conditions. This study investigates the inactivation process under
      low temperature conditions. Inactivation was caused by dissociation of tetrameric
      ASL into dimers, with increased exposure of hydrophobic areas without disturbance
      of the secondary structure or the microenvironment surrounding the key tryptophan
      residues. Most activity was retained when temperatures were changed at a rate of
      >1  degrees C/min, whilst freezing or thawing more slowly resulted in greater
      loss of activity. Inactivation was reduced by inclusion of alpha-crystallin, a
      structural protein found in ocular lenses and a member of the small heat-shock
      protein family, by stabilization of the ASL quaternary structure. In addition,
      alpha-crystallin was able to restore the function of ASL that had been
      inactivated by slow freezing and thawing. The effect of alpha-crystallin was
      similar to that of bovine serum albumin, suggesting that both proteins exerted
      their effects by hydrophobic interactions. alpha-Crystallin therefore acts as a
      cryo-preservative that protects ASL activity during freezing and thawing.

PMID- 21963435
TI  - Enzyme catalytic promiscuity: The papain-catalyzed Knoevenagel reaction.
AB  - Papain as a sustainable and inexpensive biocatalyst was used for the first time
      to catalyze the Knoevenagel reactions in DMSO/water. A wide range of aromatic,
      hetero-aromatic and alpha,beta-unsaturated aldehydes could react with less active
      methylene compounds acetylacetone and ethyl acetoacetate. The products were
      obtained in moderate to excellent yields with Z/E selectivities of up to 100:0.
      This case of biocatalytic promiscuity not only widens the application of papain
      to new chemical transformations, but also could be developed into a potentially
      valuable method for organic synthesis.

PMID- 21963436
TI  - The presence of teleost-type angiotensin components in lamprey buccal gland
      suggests a role in endocrine mimicry.
AB  - Previous characterization of a native lamprey angiotensin II (LpAng II) that
      possesses a different sequence and function than teleost-type angiotensin II (Ang
      II) has raised a question as to the role of teleost-type angiotensin peptides in
      lampreys. In this study, teleost-type angiotensin like-peptides were identified
      in the buccal gland of lampreys by immunoassays and immunohistochemistry. The
      possible sources of angiotensin like-peptides were investigated in lampreys by
      manipulating their choice of host and food. Ang II immunoreactivity (irAng II)
      was detected in the buccal gland and plasma of feeding phase sea lampreys exposed
      to Atlantic cod, but was mostly absent in fasting lamprey. Qualitatively, the
      HPLC profiles of irAng II observed in the plasma, when present, were highly
      similar to those in buccal gland, implying that the buccal gland could be a
      source of plasma Ang II. Japanese lampreys force-fed with dogfish blood had
      significantly elevated concentrations of irAng II in their buccal glands when
      compared to unfed individuals, suggesting that feeding stimuli may have enhanced
      buccal gland activity. Teleost-type Ang II-containing proteins, other than
      angiotensinogen, are present in the buccal gland as trypsinization generated Ang
      II in vitro, and the HPLC profile of these irAng II was highly comparable to
      those naturally present in the buccal gland. [Asn(1), Val(5), Thr(9)]-Ang I that
      was identified in the buccal gland of Japanese lampreys has the same amino acid
      sequence to those previously isolated from the incubation of plasma and kidney
      extract, providing an alternative explanation for the previous isolation of
      teleost-type Ang I in lampreys. irAng I and irAng II were localized in the
      granule-like structures in the apical region of the secretory epithelia,
      suggesting that these peptides may be active components of lamphredin. The
      teleost-type angiotensin peptides in the buccal gland secretion suggested that
      these host-specific peptides could be part of the endocrine mimicry strategy used
      by lampreys to evade host immune responses and reduce immune-rejection.

PMID- 21963437
TI  - [Microsurgery and burn sequelae: what is practical use?].
AB  - The use of microsurgery in the management of burn sequelae is not a new idea and
      free flaps have been used in this context since the 1970s. New technologies like
      negative pressure treatment and skin substitute have certainly decreased the
      indication of free flaps. The authors with their experience combined to a review
      of the literature, try to clarify these indications for each anatomical location.
      From a technical point of view, they find that realizing a free flap for these
      patients is more complicated (venous damage, lack of donor site who has been
      burned...). Despite this, microsurgery must still belong in the decision tree and
      there are some irreplaceable indication specially for hand reconstruction.

PMID- 21963438
TI  - Proteomic and biological characterization of the venom of the redtail coral
      snake, Micrurus mipartitus (Elapidae), from Colombia and Costa Rica.
AB  - Venoms of the redtail coral snake Micrurus mipartitus from Colombia and Costa
      Rica were analyzed by "venomics", a proteomic strategy to determine their
      composition. Proteins were separated by RP-HPLC, followed by SDS-PAGE, in-gel
      tryptic digestion, identification by MALDI or ESI tandem mass spectrometry, and
      assignment to known protein families by similarity. These analyses were
      complemented with a characterization of venom activities in vitro and in vivo.
      Proteins belonging to seven families were found in Colombian M. mipartitus venom,
      including abundant three-finger toxins (3FTx; ~60% of total proteins) and
      phospholipases A(2) (PLA(2); ~30%), with the remaining ~10% distributed among l
      amino acid oxidase, P-III metalloproteinase, Kunitz-type inhibitor, serine
      proteinase, and C-type lectin-like families. The venoms of two M. mipartitus
      specimens from Costa Rica, also referred to as M. multifasciatus in some
      taxonomic classifications, were also analyzed. Both samples were highly similar
      to each other, and partially resembled the chromatographic and identity profiles
      of M. mipartitus from Colombia, although presenting a markedly higher proportion
      of 3FTxs (~83.0%) in relation to PLA(2)s (~8.2%), and a small amount of
      acetylcholinesterase, not detected in the venom from Colombia. An equine
      antivenom against the Central American coral snake, M. nigrocinctus, did not
      recognize venom components of M. mipartitus from Colombia or Costa Rica by enzyme
      immunoassay. Four major components of Colombian M. mipartitus venom were isolated
      and partially characterized. Venomics of Micrurus species may provide a valuable
      platform for the rational design of immunizing cocktails to obtain polyspecific
      antivenoms for this highly diverse group of American elapids.

PMID- 21963439
TI  - Alternative 2-keto acid oxidoreductases in Trichomonas vaginalis: artifact of
      histochemical staining.
AB  - Trichomonas vaginalis has been reported to possess alternative 2-keto acid
      oxidoreductases (KORs). These enzymes preferentially used indolepyruvate in a
      reaction that resembled that of pyruvate:ferredoxin oxidoreductase (PFO).
      However, the KORs did not reduce ferredoxin and remained active in metronidazole
      resistant trichomonads lacking PFO. Therefore, it was proposed that the KORs may
      help trichomonads to survive in the presence of metronidazole. The KORs were
      identified using activity staining on native gels (Brown DM, Upcroft JA, Dodd HN,
      et al. Alternative 2-keto acid oxidoreductase activities in T. vaginalis. Mol
      Biochem Parasitol 1999;98:203-14). In the current study, we showed that the
      apparent KOR activity was caused by the non-enzymatic reduction of the indicator
      dye, nitroblue tetrazolium, by indolepyruvate, which is facilitated by Triton X
      100 used to prepare the membrane fractions. We could not confirm the presence of
      KORs in metronidazole-resistant T. vaginalis. The low level indolepyruvate
      dependent activity that is present in T. vaginalis strains sensitive to
      metronidazole is catalyzed by PFO, which was verified using the pure enzyme.
      Therefore, our results suggest that alternative 2-keto acid oxidoreductases do
      not exist in T. vaginalis.

PMID- 21963440
TI  - Nuclear actin-related protein is required for chromosome segregation in
      Toxoplasma gondii.
AB  - Apicomplexa parasites use complex cell cycles to replicate that are not well
      understood mechanistically. We have established a robust forward genetic strategy
      to identify the essential components of parasite cell division. Here we describe
      a novel temperature sensitive Toxoplasma strain, mutant 13-20C2, which growth
      arrests due to a defect in mitosis. The primary phenotype is the mis-segregation
      of duplicated chromosomes with chromosome loss during nuclear division. This
      defect is conditional-lethal with respect to temperature, although relatively
      mild in regard to the preservation of the major microtubule organizing centers.
      Despite severe DNA loss many of the physical structures associated with daughter
      budding and the assembly of invasion structures formed and operated normally at
      the non-permissive temperature before completely arresting. These results suggest
      there are coordinating mechanisms that govern the timing of these events in the
      parasite cell cycle. The defect in mutant 13-20C2 was mapped by genetic
      complementation to Toxoplasma chromosome III and to a specific mutation in the
      gene encoding an ortholog of nuclear actin-related protein 4. A change in a
      conserved isoleucine to threonine in the helical structure of this nuclear actin
      related protein leads to protein instability and cellular mis-localization at the
      higher temperature. Given the age of this protist family, the results indicate a
      key role for nuclear actin-related proteins in chromosome segregation was
      established very early in the evolution of eukaryotes.

PMID- 21963441
TI  - Brain connectivity and high functioning autism: a promising path of research that
      needs refined models, methodological convergence, and stronger behavioral links.
AB  - Here we review findings from studies investigating functional and structural
      brain connectivity in high functioning individuals with autism spectrum disorders
      (ASDs). The dominant theory regarding brain connectivity in people with ASD is
      that there is long distance under-connectivity and local over-connectivity of the
      frontal cortex. Consistent with this theory, long-range cortico-cortical
      functional and structural connectivity appears to be weaker in people with ASD
      than in controls. However, in contrast to the theory, there is less evidence for
      local over-connectivity of the frontal cortex. Moreover, some patterns of
      abnormal functional connectivity in ASD are not captured by current theoretical
      models. Taken together, empirical findings measuring different forms of
      connectivity demonstrate complex patterns of abnormal connectivity in people with
      ASD. The frequently suggested pattern of long-range under-connectivity and local
      over-connectivity is in need of refinement.

PMID- 21963442
TI  - Differences between effects of psychological versus pharmacological treatments on
      functional and morphological brain alterations in anxiety disorders and major
      depressive disorder: a systematic review.
AB  - The most prevalent mental disorders, anxiety and mood disorders, are associated
      with both functional and morphological brain changes that commonly involve the
      'fear network' including the (medial) prefrontal cortex, hippocampus and
      amygdala. Patients suffering from anxiety disorders and major depressive disorder
      often show excessive amygdala and reduced prefrontal cortex functioning. It is,
      however, still unclear whether these brain abnormalities disappear or diminish
      following effective treatment. This review aims to compare the effects of
      psychotherapy and pharmacotherapy on functional and morphological brain measures
      in these disorders. Sixty-three studies were included, 30 investigating
      psychotherapy effects and 33 investigating pharmacotherapy effects. Despite
      methodological differences, results suggest a functional normalization of the
      'fear network'. Pharmacotherapy particularly decreases over-activity of limbic
      structures (bottom-up effect) while psychotherapy tends to increase activity and
      recruitment of frontal areas (top-down effect), especially the anterior cingulate
      cortex. Additionally, pharmacotherapy, but not psychotherapy, has been associated
      with morphological changes, depending on the disorder. These findings suggest
      that both types of treatments normalize (functional) brain abnormalities each in
      specific ways.

PMID- 21963443
TI  - A novel splice site mutation in gene C2orf37 underlying Woodhouse-Sakati syndrome
      (WSS) in a consanguineous family of Pakistani origin.
AB  - Woodhouse-Sakati Syndrome (WSS) is a rare autosomal recessive multisystemic
      disorder that is marked by hypogonadism, alopecia, intellectual disability,
      deafness, diabetes mellitus and progressive extrapyramidal defects. Mutations in
      the gene C2orf37 are the cause of Woodhouse-Sakati syndrome. In the present
      study, a four-generation consanguineous family with clinical manifestations of
      WSS was ascertained from a remote region of Pakistan. Linkage in the family was
      tested using microsatellite markers linked to several genes involved in producing
      WSS related phenotypes. Linkage in the family was established to the gene
      C2orf37, mapped on chromosome 2q22.3-2q35. DNA sequence analysis revealed a novel
      splice site mutation involving a homozygous G->A transition in the splice donor
      site of intron 3 (c.321+1G>A) of C2orf37. This study presents a first report of
      Woodhouse-Sakati syndrome identified in Pakistani population.

PMID- 21963444
TI  - Helper-dependent canine adenovirus vector-mediated transgene expression in a
      neurodegenerative lysosomal storage disorder.
AB  - Mucopolysaccharidosis type IIIA (MPS-IIIA) is a severe neurodegenerative
      lysosomal storage disorder caused by a deficiency of N-sulfoglucosamine
      sulfohydrolase (SGSH) activity with subsequent accumulation of partially-degraded
      heparan sulfate and other glycolipids. In this study, we have evaluated a gene
      therapy approach using a helper-dependent canine adenovirus vector that expresses
      human SGSH as a means of delivering sustained transgene expression to the brain.
      Initial testing in a mixed neural cell culture model demonstrated that the vector
      could significantly increase SGSH activity in transduced cells, resulting in near
      normalization of heparan sulfate-derived fragments. While administration of
      vector by direct injection into the brain of adult MPS-IIIA mice enabled
      transgene expression for at least 8.5 months post-treatment, it was only in
      discrete areas of brain. Heparan sulfate storage was reduced in some regions
      following treatment, however there was no improvement in secondary
      neuropathological changes. These data demonstrate that helper-dependent canine
      adenovirus vectors are capable of neural transduction and mediate long-term
      transgene expression, but increased SGSH expression throughout the brain is
      likely to be required in order to effectively treat all aspects of the MPS-IIIA
      phenotype.

PMID- 21963445
TI  - Evaluation of the 16S and 12S rRNA genes as universal markers for the
      identification of commercial fish species in South Africa.
AB  - The development of DNA-based methods for the identification of fish species is
      important for fisheries research and control, as well as for the detection of
      unintentional or fraudulent species substitutions in the marketplace. The aim of
      this study was to generate a comprehensive reference database of DNA sequences
      from the mitochondrial 16S and 12S ribosomal RNA (rRNA) genes for 53 commercial
      fish species in South Africa and to evaluate the applicability of these genetic
      markers for the identification of fish at the species level. The DNA extracted
      from all target species was readily amplified using universal primers targeting
      both rRNA gene regions. Sequences from the 16S and 12S rRNA genes were submitted
      to GenBank for the first time for 34% and 53% of the fish species, respectively.
      Cumulative analysis of the 16S rRNA gene sequences revealed mean conspecific,
      congeneric and confamilial Kimura two parameter (K2P) distances of 0.03%, 0.70%
      and 5.10% and the corresponding values at the 12S level were 0.03%, 1.00% and
      5.57%. K2P neighbour-joining trees based on both sequence datasets generally
      clustered species in accordance with their taxonomic classifications. The
      nucleotide variation in both the 16S and 12S sequences was suitable for
      identifying the large majority of the examined fish specimens to at least the
      level of genus, but was found to be less useful for the explicit differentiation
      of certain congeneric fish species. It is recommended that one or more faster
      evolving DNA regions be analysed to confirm the identities of closely-related
      fish species in South Africa.

PMID- 21963446
TI  - Species-specific differences in the processing of acid alpha-glucosidase are due
      to the amino acid identity at position 201.
AB  - Acid alpha-glucosidase (GAA) is a lysosomal enzyme that hydrolyzes glycogen to
      glucose. Deficiency of GAA causes Pompe disease. Mammalian GAA is synthesized as
      a precursor of ~110,000 Da that is N-glycosylated and targeted to the lysosome
      via the M6P receptors. In the lysosome, human GAA is sequentially processed by
      proteases to polypeptides of 76-, 19.4-, and 3.9-kDa that remain associated.
      Further cleavage between R(200) and A(204) inefficiently converts the 76-kDa
      polypeptide to the mature 70-kDa form with an additional 10.4-kDa polypeptide.
      GAA maturation increases its affinity for glycogen by 7-10 fold. In contrast to
      human GAA, processing of bovine and hamster GAA to the 70-kDa form is more rapid.
      A comparison of sequences surrounding the cleavage site revealed human GAA
      contains histidine at 201 while other species contain hydrophobic amino acids at
      position 201 in the otherwise conserved sequence. Recombinant human GAA (rhGAA)
      containing the H201L substitution was expressed in 293 T cells by transfection.
      Pulse chase experiments in 293 T cells expressing rhGAA with or without the H201L
      substitution revealed rapid processing of rhGAA(H201L) but not rhGAA(WT) to the
      70-kDa form. Similarly, when GAA precursor was endocytosed by human Pompe
      fibroblasts rhGAA(H201L) but not rhGAA(WT) was rapidly converted to the 70-kDa
      mature GAA. These studies indicate that the amino acid at position 201 influences
      the rate of conversion of 76-kDa GAA to 70-kDa GAA. The GAA sequence rather than
      the lysosomal protease environment explains the predominance of the 76-kDa form
      in human tissues.

PMID- 21963447
TI  - Cell death pathology: cross-talk with autophagy and its clinical implications.
AB  - Autophagy is a self-digesting mechanism that cells adopt to respond to stressful
      stimuli. Morphologically, cells dying by autophagy show multiple cytoplasmic
      double-membraned vacuoles, and, if prolonged, autophagy can lead to cell death,
      "autophagic cell death". Thus, autophagy can act both as a temporary protective
      mechanism during a brief stressful episode and be a mode of cell death in its own
      right. In this mini-review we focus on recent knowledge concerning the connection
      between autophagy and programmed cell death, evaluating their possible
      implications for therapy in pathologies like cancer and neurodegeneration.

PMID- 21963448
TI  - A survey of expectations and understanding of palliative radiotherapy from
      patients with advanced cancer.
AB  - AIMS: To assess patients' understanding of their illness and expectations of
      palliative radiotherapy for symptomatic metastases before and after consultation
      and to explore the relationship between response and demographics/Edmonton
      Symptom Assessment Scale (ESAS) scores. MATERIALS AND METHODS: In total, 100
      participants completed a survey before and after consultation from March to
      October 2009. Descriptive statistics and statistical analyses were conducted to
      compare responses and to determine any relationship between responses and
      demographics or ESAS variables. RESULTS: Up to 25% believed their cancer was
      curable; there was no change in belief that radiotherapy would cure their cancer
      (17% before and 15% after) or prolong their life (40% before and 45% after).
      There were significant differences in radiotherapy expectation for symptom relief
      (P=0.0094) and for patients who did not know the role of radiotherapy (P=0.0025).
      Patient anxiety was reduced after consultation on questions about radiotherapy
      (P<0.001), concerns on effectiveness (P<0.0001) and side-effects of treatment
      (P<0.0001); 96, 24 and 46% said after consultation that they were satisfied with
      information from the team, better understood their diagnosis of cancer and the
      role of radiotherapy, respectively. CONCLUSION: A significant proportion of
      patients with advanced disease believe their cancer is curable, expect that
      radiotherapy will cure their cancer and prolong their life despite understanding
      the intent of radiotherapy is for symptom relief. After consultation, patients
      say they have a better understanding of their cancer and feel more confident
      about treatment. More work is needed to improve patients' understanding of their
      illness and expectations of the role of palliative radiotherapy.

PMID- 21963449
TI  - Two-dimensional trajectory analysis of the diatom Navicula sp. using a micro
      chamber.
AB  - We describe a trajectory analysis of diatom cell locomotion by combining a micro
      chamber and two-dimensional position coordinate analysis. By shutting cells in a
      micro chamber, continuous microscopic observation of Navicula sp. cells was
      possible. The trajectory of each cell was visualized once every second by using
      position coordinate analysis although time resolution of previous papers were
      range of minutes. Our data revealed frequent change of movement direction.
      Furthermore, the correlation between the distances moved, the velocity, and the
      acceleration of the cells was discussed in detail.

PMID- 21963450
TI  - Changes of hepatic lactoferrin gene expression in two mouse models of the acute
      phase reaction.
AB  - Lactoferrin (Ltf), an iron binding glycoprotein, is a pleiotropic molecule whose
      serum concentration increases under acute phase conditions. The physiological
      roles of this protein have been well elucidated, but the source and serum
      regulation of Ltf gene expression have not been investigated in detail as part of
      the acute phase reaction (APR). In the current work, the changes in hepatic Ltf
      gene-expression during turpentine oil- (TO-) or LPS-induced APR were
      investigated. Ltf was upregulated at both the mRNA and protein levels in the
      liver of TO- and LPS-treated wild type (WT) mice. The pattern of induction
      however was different in both animal models indicating distinctive signalling
      patterns resulting in an acute phase reaction. Cytokines are the core regulators
      of APR. Among the major cytokines, IL-6 is an important signalling molecule,
      which also regulates iron homeostasis in response to an inflammatory situation.
      In this study, the administration of IL-6 induced Ltf gene expression in the
      liver of WT mice, in murine hepatocytes and in hepa 1-6 cells. Ltf-gene
      expression was upregulated also in the liver of TO- and LPS-treated IL-6 knockout
      (KO) mice. The increase in serum Ltf after LPS injection was greater than after
      TO-injection both in WT and IL-6-KO mice. To evaluate the contribution of other
      acute phase cytokines in the regulation of Ltf-gene-expression in the liver, both
      in vitro and in vivo studies with IL-1beta, TNF-alpha, or IFN-gamma were
      performed. The results demonstrate that TNF-alpha and IFN-gamma also upregulated
      Ltf-gene-expression, while IL-1beta has no role in the regulation of Ltf-gene
      expression.

PMID- 21963451
TI  - Antihyperglycemic activity and antidiabetic effect of methyl caffeate isolated
      from Solanum torvum Swartz. fruit in streptozotocin induced diabetic rats.
AB  - Natural remedies from medicinal plants are considered to be effective and safe
      alternatives to treat diabetes mellitus. Solanum torvum Swartz. fruit is widely
      used in the traditional system of medicine to treat diabetes. In the present
      study methyl caffeate, isolated from S. torvum fruit, was screened for its
      efficacy in controlling diabetes in animal models. Antihyperglycemic effect of
      methyl caffeate was studied in normal glucose-fed rats. The effects of oral
      administration of methyl caffeate (10, 20 and 40 mg/kg) for 28 days on body
      weight, fasting blood glucose, plasma insulin, hemoglobin, glycated hemoglobin,
      total protein, hepatic glycogen and carbohydrate metabolism enzymes in
      streptozotocin induced diabetic rats were investigated. Histological observations
      in the pancreas and GLUT4 expression in skeletal muscles were also studied.
      Methyl caffeate at 40 mg/kg significantly prevented the increase in blood glucose
      level after glucose administration at 60 min in comparison to the hyperglycemic
      control group. In streptozotocin induced diabetic rats, methyl caffeate produced
      significant reduction in blood glucose and increased body weight. The levels
      and/or activities of other biochemical parameters were near normal due to
      treatment with methyl caffeate. Methyl caffeate treated diabetic rats showed
      upregulation of GLUT4 and regeneration of beta-cells in the pancreas. These
      results substantiated that methyl caffeate possessed hypoglycemic effect, and it
      could be developed into a potent oral antidiabetic drug.

PMID- 21963452
TI  - Naringenin suppresses the production of thymic stromal lymphopoietin through the
      blockade of RIP2 and caspase-1 signal cascade in mast cells.
AB  - Thymic stromal lymphopoietin (TSLP) plays a critical role in allergic diseases
      such as atopic dermatitis, asthma, and chronic obstructive pulmonary disease.
      Naringenin has various effects such as anti-atherogenic, anti-oxidant, and anti
      inflammatory effects. However, the effect of naringenin on the production of TSLP
      has not been clarified. Thus, we investigated how naringenin inhibits the
      production of TSLP in the human mast cell line (HMC-1) cells. Naringenin
      inhibited the production and mRNA expression of TSLP in HMC-1 cells. The maximal
      inhibition rate of TSLP production by naringenin (100 MUM) was 62.27 +/- 10.79%.
      Naringenin also inhibited the nuclear factor-kappaB luciferase activity induced
      by phorbol myristate acetate plus A23187. In the activated HMC-1 cells, the
      activations of receptor-interacting protein (RIP)2 and caspase-1 were increased,
      whereas the activations of RIP2 and caspase-1 were decreased by pretreatment with
      naringenin. These results suggest that naringenin can be used to treat
      inflammatory and atopic diseases through the inhibition of TSLP.

PMID- 21963453
TI  - Snail-1 regulates VDR signaling and inhibits 1,25(OH)-D3 action in osteosarcoma.
AB  - Previous research has shown that vitamin D could suppress proliferation,
      migration and invasion of cancers, but the effects of vitamin D may be related to
      the expression of Snail-1, which could inhibit the expression of the vitamin-D
      gene receptor (VDR). Snail-1 is overexpressed in osteosarcoma, this study was
      conducted to determine whether inhibiting Snail-1 could increase the role of
      vitamin D as an anti- osteosarcoma agent. We used stable transfection of the
      SaOS2 cell line as in vitro model to study the effect of 1,25(OH)-D3, which is
      the most active metabolite of vitamin D. The in vitro antiproliferative, pro
      apoptotic and inhibiting of invasion effects were examined. The effects of
      1,25(OH)-D3 on the expression of beta-catenin signaling pathways were also
      studied. Then in vivo antiproliferative effect of 1,25(OH)-D3 was also detected
      in nude mice injected with either mock-infected or Snail-1 SaOS2 cells. We found
      that inhibition of Snail-1 signaling by transfection could increase the
      expression of VDR, enhance the anti-proliferative activity of 1,25(OH)-D3 in
      osteosarcoma cells, and induce apoptosis and lower invasion in vitro. The effect
      of 1,25(OH)-D3 was also associated with decreased expression of beta-catenin
      signaling, which is related to VDR signaling. In vivo, the effect of
      antiproliferative was higher in mice injected with either Snail-1-infected cells
      than with mock-infected cells. Our findings suggest that canonical Snail
      1/VDR/beta-catenin signaling reflects an important underlying mechanism of
      osteosarcoma progression. Therefore, strategies to suppress Snail-mediated
      signaling may lead to the better action of 1,25(OH)-D3 as an anti osteosarcoma
      treatment.

PMID- 21963454
TI  - The effect of dehydroleucodine in adipocyte differentiation.
AB  - Dehydroleucodine (DhL) is a sesquiterpene lactone of the guaianolide group with
      gastric cytoprotective activity. Recent studies have also demonstrated that DhL
      inhibits the proliferation of vascular smooth muscle cells. In this study we
      examined the effect of DhL in the differentiation of 3T3-L1 preadipocytes. The
      addition of DhL significantly inhibited the differentiation of 3T3-L1
      preadipocytes along with a significant decrease in the accumulation of lipid
      content by a dramatic downregulation of the expression of adipogenic-specific
      transcriptional factors PPARgamma and C-EBPalpha. However, phosphorylation of
      AMPKalpha, Erk1/2 and Akt1 was not inhibited by DhL treatment. Interestingly, we
      also found that 11,13-dihydrodehydroleucodine, a derivative of DhL with
      inactivated alpha-methylene-gamma-lactone function, also inhibited the
      differentiation of 3T3-L1 preadipocytes. Taken together, these data suggest that
      DhL has an important inhibitory effect in cellular pathways regulating adipocyte
      differentiation by modulating the PPARgamma expression, which is known to play a
      pivotal role during adipogenesis.

PMID- 21963455
TI  - The novel trisubstituted pyran derivative D-142 has triple monoamine reuptake
      inhibitory activity and exerts potent antidepressant-like activity in rodents.
AB  - Major depression disorder is a significant health problem with 10-20% of all
      adults suffering from this disease. The underlying causes of depression are still
      unclear and 15% of depressed patients are resistant to all known therapies.
      Monoamine therapies have so far been the most successful approach for treating
      depression. Triple monoamine reuptake inhibitors have recently been implicated in
      generation of potent antidepressant activity while possibly exhibiting a low side
      effect profile in addition to treating anhedonia. The additional, previously
      under-appreciated involvement of dopaminergic systems in depression prompted our
      efforts to develop novel asymmetric trisubstituted and disubstituted pyran
      derivatives as triple reuptake inhibitors. One of the lead compounds, D-142,
      exhibited uptake inhibition (K(i)) values of 29.3 nM, 14.7 nM and 59.3 +/- 13.7
      nM for norepinephrine, serotonin and dopamine transporters, respectively. Its
      affinity for serotonin transporter was comparable to fluoxetine, a well known
      SSRI. In the rat forced swimming test, compound D-142 exhibited potent
      antidepressant activity in the dose range tested (2.5, 5 and 10mg/kg) and was far
      more efficacious than the reference compound imipramine. In the mouse tail
      suspension test, compound D-142 reduced immobility in a dose (2.5, 5 and 10mg/kg)
      dependent manner, indicating a potent antidepressant effect. In locomotor
      activity tests, compound D-142 did not exhibit any stimulation in the same dose
      ranges. In the extended CNS receptors screening assay this molecule exhibited
      little or no non-specific interaction in the CNS, indicating high specificity for
      monoamine transporters. These results advance D-142 as a potential potent
      antidepressant.

PMID- 21963457
TI  - Complement activation by polyethoxylated pharmaceutical surfactants: Cremophor
      EL, Tween-80 and Tween-20.
AB  - Immunosafety analysis of pharmaceutical surfactants is an important step in
      understanding the complex mechanisms by which they induce side effects in
      susceptible patients. This paper provides experimental evidences that
      polyethoxylated surfactants, Cremophor-EL and Tween-80, also known as Polysorbate
      80, activate the complement system in vitro, in normal human serum and plasma.
      They appeared to be more efficient reactogens than their structural homolog,
      Tween-20. Cremophor-EL and Tween-80 promoted the generation of biologically
      active complement products, C3a, C5a and C5b-9. Consistently, Paclitaxel and
      Taxotere (Docetaxel), pharmaceuticals formulated in Cremophor-EL and Tween-80,
      activated the complement system in similar extent. Moreover, comparison of serum
      reactivity against the drug-loaded and drug-free formulations exhibited a
      significant linear correlation. Taken together, these results are consistent with
      the hypothesis that therapeutic side effects, such as acute hypersensitivity and
      systemic immunostimulation, caused by intravenous nanomedicines containing
      polyethoxylated detergents such as Cremophor-EL and Tween-80, can be attributed
      to complement activation-derived inflammatory mediators.

PMID- 21963456
TI  - Estimation of P-glycoprotein-mediated efflux in the oral absorption of P-gp
      substrate drugs from simultaneous analysis of drug dissolution and permeation.
AB  - The purpose of this study was to establish an in vitro system that evaluates the
      effects of P-glycoprotein (P-gp)-mediated efflux on the oral absorption of P-gp
      substrates. An in vitro system (dissolution/permeation system, D/P system) was
      developed that consisted of apical and basal chambers and a Caco-2 cell monolayer
      mounted between the chambers. Both sides of the monolayer were filled with
      physiological solution and were stirred at 200rpm. The dissolution in the apical
      medium and permeation to the basal medium were monitored for 2h after P-gp
      substrates were applied to the apical side of the system. When erythromycin
      existed in the apical medium, the permeations of fexofenadine and talinolol were
      significantly enhanced without change in their dissolution. The prediction of
      oral absorptions of fexofenadine and talinolol from in vitro data indicated that
      co-administration of erythromycin results in 2.1- and 1.9-fold higher oral
      absorptions, respectively. Moreover, the D/P system could estimate the effect of
      cremophor EL on the oral absorption of saquinavir. These estimations corresponded
      well to in vivo human observations. Our in vitro system is useful in assessment
      of the effect of P-gp-mediated efflux on in vivo oral absorption of P-gp
      substrates.

PMID- 21963458
TI  - Osteoclasts in bone modeling, as revealed by in vivo imaging, are essential for
      organogenesis in fish.
AB  - Bone modeling is the central system controlling the formation of bone including
      bone growth and shape in early development, in which bone is continuously
      resorbed by osteoclasts and formed by osteoblasts. However, this system has not
      been well documented, because it is difficult to trace osteoclasts and
      osteoblasts in vivo during development. Here we showed the important role of
      osteoclasts in organogenesis by establishing osteoclast-specific transgenic
      medaka lines and by using a zebrafish osteoclast-deficient line. Using in vivo
      imaging of osteoclasts in the transgenic medaka carrying an enhanced GFP (EGFP)
      or DsRed reporter gene driven by the medaka TRAP (Tartrate-Resistant Acid
      Phosphatase) or Cathepsin K promoter, respectively, we examined the maturation
      and migration of osteoclasts. Our results showed that mononuclear or
      multinucleated osteoclasts in the vertebral body were specifically localized at
      the inside of the neural and hemal arches, but not at the vertebral centrum.
      Furthermore, transmission electron microscopic (TEM) analyses revealed that
      osteoclasts were flat-shaped multinucleated cells, suggesting that osteoclasts
      initially differentiate from TRAP-positive mononuclear cells residing around
      bone. The zebrafish panther mutant lacks a functional c-fms (receptor for
      macrophage colony-stimulating factor) gene crucial for osteoclast proliferation
      and differentiation and thus has a low number of osteoclasts. Analysis of this
      mutant revealed deformities in both its neural and hemal arches, which resulted
      in abnormal development of the neural tube and blood vessels located inside these
      arches. Our results provide the first demonstration that bone resorption during
      bone modeling is essential for proper development of neural and vascular systems
      associated with fish vertebrae.

PMID- 21963459
TI  - Identification of a retina-specific Otx2 enhancer element active in immature
      developing photoreceptors.
AB  - The homeodomain protein, Otx2, is a critical regulator of vertebrate
      photoreceptor genesis. However, the genetic elements that define the expression
      of Otx2 during photoreceptor development are unknown. Therefore, we sought to
      identify an Otx2 enhancer element that functions in photoreceptor development in
      order to better understand this specification event. Using the technique of
      electroporation, we tested a number of evolutionarily conserved elements (ECRs)
      for expression in the developing retina, and identified ECR2 as having robust
      activity in the retina. We have characterized this element using a number of
      assays, including Cre-fate mapping experiments. We found that ECR2 recapitulates
      expression/function of Otx2 primarily in newly postmitotic photoreceptor cells
      (PRs), as well as in a subset of retinal progenitor cells (RPCs). ECR2 was also
      found to be expressed in a subset of horizontal cells (HCs), in keeping with the
      role of Otx2 in HC development. Furthermore, we determined that the ECR2 element
      is not active in other Otx2-positive cells such as retinal bipolar cells (BPs),
      retinal pigmented epithelium (RPE), or the tectum, suggesting that the
      transcriptional networks controlling Otx2 expression in these cells are unique
      from those of developing PRs and HCs. These results reveal a distinct molecular
      state in dividing retinal cells and their newly postmitotic progeny, and provide
      genetic access to an early and critical transcriptional node involved in the
      genesis of vertebrate PRs.

PMID- 21963460
TI  - Early postnatal changes of lipoprotein subclass profile in late preterm infants.
AB  - BACKGROUND: Late preterm infants (LPIs; 34-37 gestational weeks at birth) have
      higher risk for several morbidities than do term infants (TIs). It has been
      suggested that a cholesterol and fatty acid supply may improve their outcomes. We
      investigated the lipoprotein subclass profile in LPIs to evaluate their early
      postnatal lipid metabolism. METHODS: Eighty-one infants (25 LPIs, 56 TIs) were
      included. Cholesterol and triglyceride (TG) concentrations in 12 lipoprotein
      subclasses were measured at birth and at 1 month using HPLC. RESULTS: In LPIs,
      the cord blood exhibited higher cholesterol concentrations in medium and large
      subclasses of very low-density lipoprotein (VLDL), low-density lipoprotein (LDL)
      and high-density lipoprotein (HDL) compared to the values in TIs. During the
      first month of life, LPIs had greater increases in cholesterol concentrations of
      medium and large subclasses of VLDL than TIs, whereas postnatal increases in
      cholesterol concentrations of medium and large subclasses of LDL and HDL were
      smaller. TG concentrations were not different in each VLDL subclass at birth and
      at 1 month. CONCLUSIONS: In LPIs, cord blood lipoprotein subclass profiles and
      the early postnatal change exhibited different, especially in cholesterol
      concentrations.

PMID- 21963461
TI  - Genetic variation, gene-expression and circulating levels of matrix
      metalloproteinase-9 in patients with stable coronary artery disease.
AB  - BACKGROUND: Mediators involved in atherosclerosis and plaque rupture may have
      importance as risk markers for coronary artery disease (CAD). We have
      investigated the influence of matrix metalloproteinase (MMP)-9 genetic variations
      on gene- and protein expression in stable CAD patients. METHODS: The promoter 
      1562C/T and exon 6 R279Q A/G polymorphisms were determined in 1001 patients with
      angiographically verified stable CAD and in 204 healthy controls. Genotype and
      gene-expression were determined by real-time PCR. Serum levels of MMP-9 and its
      inhibitor TIMP-1were measured immunologically and by zymography (MMP-9 activity).
      RESULTS: None of the polymorphisms associated with the presence of CAD,
      myocardial infarction or type 2 diabetes, whereas the variant allele of the R279Q
      polymorphism associated with hypertension (adjusted p=0.015). The T- and G
      alleles associated with lower and higher mRNA levels, respectively (p<0.005
      both), also shown in an experimental ex-vivo LPS stimulated model. T-allele
      carriers had higher concentrations of MMP-9 (adjusted p=0.032) and the GG
      genotype induced lower MMP-9 gelatinolytic activity (p=0.01). Higher MMP-9 gene
      expression and TIMP-1 levels were observed in patients with previous myocardial
      infarction, the latter also was elevated in diabetics (<0.05, all). CONCLUSION:
      The investigated MMP-9 polymorphisms influenced gene- and protein expression
      differently and the R279Q polymorphism associated significantly with
      hypertension.

PMID- 21963462
TI  - Betaine homocysteine methyl transferase 1, a novel auto-antigen associated with
      anti-Golgi immune reactivity.
AB  - Anti-Golgi antibodies are rare autoantibodies that have been described in
      systemic autoimmune diseases. Not all Golgi auto-antigens are known. The
      objective of this study was to identify a novel auto-antigen associated with anti
      Golgi immune reactivity. Sera from a patient with Golgi immune reactivity and
      from a control individual were used for Western blotting after 2-dimensional gel
      separation of a rat Golgi-enriched extract. Betaine homocysteine S
      methyltransferase 1 (BHMT1) was identified as an auto-antigen by MALDI-TOF/TOF
      mass spectrometry. Using human recombinant BHMT1, a strong positive blotting
      signal was obtained with serum from the patient but not from a control. Pre
      absorption of the serum sample with reactivity to BHMT1 with recombinant human
      BHMT1 resulted in decreased reactivity on Western blotting and in disappearance
      of the Golgi-like pattern on indirect immunofluorescence. Using
      immunocytochemistry, we confirmed the subcellular localization of BHMT1 to the
      Golgi apparatus. Antibodies to BHMT1 were found in four of 80 samples with a
      Golgi-pattern on indirect immunofluorescence. The antibodies were not associated
      with a specific clinical condition. We identified BHMT1 as a novel auto-antigen
      associated with anti-Golgi immune reactivity.

PMID- 21963463
TI  - Discrepant intact parathyroid hormone result by immunoassay.

PMID- 21963464
TI  - Novel mutations in xanthine dehydrogenase/oxidase cause severe hypouricemia:
      biochemical and molecular genetic analysis in two Czech families with xanthinuria
      type I.
AB  - BACKGROUND: The article describes the clinical, biochemical, enzymological and
      molecular genetics findings in two patients from two families with xanthinuria
      type I. METHODS: Biochemical analysis using high performance liquid
      chromatography, allopurinol loading test and analysis of xanthine oxidase
      activity in plasma and of uromodulin excretion in urine were performed.
      Sequencing analysis of the xanthine dehydrogenase gene and the haplotype and
      statistical analyses of consanguinity were performed. RESULTS: Probands showed
      extremely low concentrations of uric acid, on seven occasions under the limit of
      detection. The concentration of uric acid in 38-year-old female was 15 MUmol/L in
      serum and 0.04 mmol/L in urine. Excretion of xanthine in urine was 170 mmol/mol
      creatinine. The concentration of uric acid in 25-year-old male was 0.03 mmol/L in
      urine. Excretion of xanthine in urine was 141 mmol/mol creatinine. The
      allopurinol loading test confirmed xanthinuria type I. The xanthine oxidase
      activities in patients were 0 and 0.4 pmol/h/mL of plasma. We found three
      nonsense changes: p.P214QfsX4 and unpublished p.R825X and p.R881X. CONCLUSIONS:
      We found two nonconsanguineous compound heterozygotes with xanthinuria type I
      caused by three nonsense changes. The methods used did not confirm consanguinity
      in the probands, thus there might be an unconfirmed biological relationship or
      mutational hotspot.

PMID- 21963465
TI  - Preparation of highly purified monomeric human serum albumin as secondary
      reference material for standardization of urinary albumin immunoassays.
AB  - BACKGROUND: International external quality assessments have shown variation in
      results of urinary albumin among various immunoassays. A well-defined candidate
      reference material for urine albumin (cRM-UA) was prepared to improve
      standardization. METHODS: cRM-UA was prepared from a commercially available
      preparation of human serum albumin by using gel-filtration HPLC. The value was
      assigned by transfer from ERM-DA470 using immunoassay systems qualified based on
      the linearity and variability observed in dilution tests of pooled urine and the
      calibrators. Effectiveness of recalibration using the cRM-UA was evaluated by
      measuring 129 urine specimens. RESULTS: The cRM-UA had a monomeric albumin peak
      which accounted for 98.9% of the total area by gel filtration HPLC. The
      lyophilized preparation of the cRM-UA had suitable homogeneity, and short- and
      long-term stability. Nine of 14 immunoassays met the criteria were used for value
      assignment. The assigned concentration was 225.1+/-9.11 mg/l [mean+/-U: expanded
      uncertainty with k=2] when reconstituted with 3.00 ml of purified water on weight
      basis. Recalibration of 7 qualified immunoassays using the cRM-UA resulted in
      between-method CV of 6.6%. CONCLUSIONS: The cRM-UA was successful in achieving
      standardization of urine albumin results among 7 immunoassays which possess
      performance attributes representing uniform reactivity to both cRM-UA and
      clinical urine samples.

PMID- 21963466
TI  - Relevance of Radiocaesium Interception Potential (RIP) on a worldwide scale to
      assess soil vulnerability to 137Cs contamination.
AB  - The extent of radiocaesium retention in soil is important to quantify the risk of
      further foodchain contamination. The Radiocaesium Interception Potential (RIP 
      Cremers et al., 1988, Nature 335, 247-249) is an intrinsic soil parameter which
      can be used to categorize soils or minerals in terms of their capacity to
      selectively adsorb radiocaesium. In this study, we measured RIP for a large soil
      collection (88 soil samples) representative of major FAO soil reference groups on
      a worldwide scale and tested the possibility to predict the RIP on the basis of
      other easily accessible or measurable soil data. We also compared RIP values with
      those obtained from separate chemical extraction experiments. The range of
      measured RIP values (1.8-13300 mmol kg(-1)) was shown to include nearly all
      possible cases of agricultural soil contamination. Only Podzols, Andosols and
      Ferralsols were clearly characterized by a very low RIP (<2000 mmol kg(-1)). On a
      worldwide scale, RIP was in fact slightly related to soil reference type or other
      simple major physicochemical parameters such as clay percentage or organic
      matter. Conversely our results indicated a link between the RIP and radiocaesium
      extractability across very different soils. We showed that, with the proposed
      scale of RIP values, a simple acid extraction method can provide an operational
      result highly predictive of potential RIP despite very contrasting soil
      properties. The RIP could be estimated from the empirical equation: RIP = (
      31.701 * log(AER) + 58.886)(2) where AER is the fraction of acid-extractable
      radiocaesium.

PMID- 21963467
TI  - Multi-equilibrium system based on sertraline and beta-cyclodextrin supramolecular
      complex in aqueous solution.
AB  - Sertraline (SRT) is a widely used antidepressant whose poor solubility in water
      limits its oral applicability. Thus, the aim of this work was the evaluation of a
      multi-equilibrium system based on beta-cyclodextrin (betaCD) and SRT. The
      inclusion compounds (ICs) were investigated by infrared spectroscopy, isothermal
      titration calorimetry (ITC) and (1)H and 2D ROESY nuclear magnetic resonance
      experiments. SRT solubility was predicted in vitro in water and biomimetic
      fluids. The SRT in presence of betaCD at 1:1 and 1:2 molar ratios was more
      soluble than free SRT in all biomimetics media investigated. The FTIR-HATR showed
      that betaCD nuC-O-C stretching band was reduced in presence of SRT, suggesting
      the interactions between them. Additionally, titration process and Job's plot
      provided information on the ICs stoichiometry and evidenced the multi-equilibrium
      coexistence in aqueous solution. According to the ITC, SRT:betaCD interaction
      process was spontaneous and exothermic with a high affinity binding constant
      (K=14,726 M(-1)). Additionally, the stoichiometry coefficient (n) was 1.63, which
      was comparable to that found by FITR-HATR. The (1)H and 2D ROESY verified
      multiple SRT sites included into the host cavity. Theoretical calculations
      depicted the relative energy of different proposed ICs structures, in which the
      1:2 IC was the most stable.

PMID- 21963468
TI  - Transdermal and transbuccal drug delivery systems: enhancement using
      iontophoretic and chemical approaches.
AB  - We investigated the enhancement effect of chemical enhancers and iontophoresis on
      the in vitro transdermal and transbuccal delivery of lidocaine HCl (LHCl),
      nicotine hydrogen tartrate (NHT), and diltiazem HCl (DHCl) using porcine skin and
      buccal tissues. Dodecyl 2-(N,N-dimethylamino) propionate (DDAIP), dodecyl-2-(N,N
      dimethylamino) propionate hydrochloride (DDAIP HCl), N-(4-bromobenzoyl)-S,S
      dimethyliminosulfurane (Br-iminosulfurane), and azone (laurocapram) were used as
      chemical enhancers. The study results showed that the application of
      iontophoresis at either 0.1 mA or 0.3 mA significantly enhanced transdermal and
      transmucosal delivery of LHCl, NHT and DHCl. It was also demonstrated that
      iontophoresis had a more pronounced enhancement effect on transdermal delivery
      than on transbuccal delivery of LHCl, NHT and DHCl. In addition, DDAIP HCl was
      found to be the most effective enhancer for transbuccal delivery of LHCl and NHT.

PMID- 21963469
TI  - The kinetics of cohesive powder de-agglomeration from three inhaler devices.
AB  - PURPOSE: The purpose of the current investigation is to understand the kinetics
      of de-agglomeration (k(d)) of micronised salbutamol sulphate (SS) and lactohale
      300 (LH300) under varying air flow rates (30-180l min(-1)) from three dry powder
      inhaler devices (DPIs), Rotahaler (RH), Monodose Inhaler (MI) and Handihaler
      (HH). RESULTS: Cumulative fine particle mass vs. time profiles were obtained from
      the powder concentration, emitted mass and volume percent <5.4 MUm, embedded in
      the particle size distributions of the aerosol at specific times. The rate of de
      agglomeration (k(d)), estimated from non-linear least squares modelling,
      increased with increasing air flow rates. The k(d)vs. air flow rate profiles of
      SS and LH300 were significantly different at high air flow rates. The k(d) was
      highest from RH and lowest from MI. Differences in k(d) between the devices were
      related to device mode of operation while the differences between the materials
      were due to the powder bed structure. CONCLUSION: This approach provided a
      methodology to measure the rate constant for cohesive powder de-agglomeration
      following aerosolisation from commercial devices and an initial understanding of
      the influence of device, air flow rate and material on these rate constants.

PMID- 21963470
TI  - Evaluation of the immunogenicity and in vivo toxicity of the antimicrobial
      peptide P34.
AB  - Immunogenicity and toxicity of antimicrobial peptide P34 were evaluated in vivo.
      BALB/c mice were inoculated intraperitoneally with peptide P34 alone and
      associated with Freund's adjuvant. For acute toxicity testing, different
      concentrations of the peptide P34 (82.5, 165.0, 247.5 and 330.0mg/kg) were orally
      administered. To evaluate the sub-chronic toxicity the tested dose of 0.825
      mg/kg/day of the peptide P34 or nisin were administered for 21 days. There were
      no hypersensitivity reactions or significant increase in antibody titer during
      the immunogenicity experiment or death of animals during the acute or sub-chronic
      toxicity tests. The LD(50) was higher than 332.3 +/- 0.76 mg/kg. No significant
      changes in serum biochemical parameters were observed in the animals treated with
      the peptide P34 unlike nisin-treated group showed a significant increase in
      alanine transaminase levels in comparison to controls. The group treated with
      0.825 mg/kg/day of nisin showed histological changes in the spleen, skin and
      liver. In the group treated with peptide P34 histological changes in the spleen
      were observed, with the presence of megakaryocytes. Few studies report the use of
      animal models to evaluate the in vivo toxicity of antimicrobial peptides and such
      investigation is an essential step to ensure it safe use in foods.

PMID- 21963471
TI  - Investigating the interactions of amino acid components on a mannitol-based spray
      dried powder formulation for pulmonary delivery: A design of experiment approach.
AB  - Combining an amino acid and a sugar is a known strategy in the formulation of
      spray or freeze dried biomolecule powder formulations. The effect of the amino
      acid leucine in enhancing performance of spray-dried powders has been previously
      demonstrated, but interaction effects of several constituents which may provide
      multiple benefits, are less well-understood. A 3 factor 2 level (2(3)) factorial
      design was used to study the effects of leucine, glycine and alanine in a
      mannitol-based dry powder formulation on particle size, aerosolisation, emitted
      dose and cohesion. Other qualitative tests including scanning electronic
      microscopy and X-ray powder diffraction were also conducted on the design of
      experiment (DoE) trials. The results show that the use of glycine and/or alanine,
      though structurally related to leucine, did not achieve similar aerosol
      performance enhancing effects, rather the particle formation was hindered.
      However, when used in appropriate concentrations with leucine, the combination of
      amino acids produced an enhanced performance regardless of the presence of
      glycine and/or alanine, yielding significantly modified particle properties. The
      results from the DoE analyses also revealed the lack of linearity of effects for
      certain responses with a significant curvature in the model which would otherwise
      not be discovered using a trial-and-error approach.

PMID- 21963472
TI  - Impact of acoustic airflow nebulization on intrasinus drug deposition of a human
      plastinated nasal cast: new insights into the mechanisms involved.
AB  - PURPOSE: The impact of 100 Hz (Hertz) acoustic frequency airflow on sinus drug
      deposition of aerosols was investigated using a human plastinated nasal cast. The
      influence of drug concentration and endonasal anatomical features on the sinus
      deposition enhanced by the 100 Hz acoustic airflow was also examined. METHODS:
      Plastinated models were anatomically, geometrically and aerodynamically validated
      (endoscopy, CT scans, acoustic rhinometry and rhinomanometry). Using the
      gentamicin as a marker, 286 experiments of aerosol deposition were performed.
      Changes of airborne particles metrology produced under different nebulization
      conditions (100 Hz acoustic airflow and gentamicin concentration) were also
      examined. RESULTS: Aerodynamic and geometric investigations highlighted a global
      behaviour of plastinated models in perfect accordance with a nasal decongested
      healthy subject. The results of intrasinus drug deposition clearly demonstrated
      that the aerosols can penetrate into the maxillary sinuses. The 100 Hz acoustic
      airflow led to increase the deposition of drug into the maxillary sinuses by a
      factor 2-3 depending on the nebulization conditions. A differential intrasinus
      deposition of active substance depending on maxillary ostium anatomical features
      and drug concentration was emphasized. CONCLUSION: The existence of a specific
      transport mechanism of penetration of nebulized particles delivered with acoustic
      airflow was proposed.

PMID- 21963473
TI  - Optimisation of spray drying process conditions for sugar nanoporous
      microparticles (NPMPs) intended for inhalation.
AB  - The present study investigated the effect of operating parameters of a laboratory
      spray dryer on powder characteristics, in order to optimise the production of
      trehalose and raffinose powders, intended to be used as carriers of biomolecules
      for inhalation. The sugars were spray dried from 80:20 methanol:n-butyl acetate
      (v/v) solutions using a Buchi Mini Spray dryer B-290. A 2(4) factorial design of
      experiment (DOE) was undertaken. Process parameters studied were inlet
      temperature, gas flow rate, feed solution flow rate (pump setting) and feed
      concentration. Resulting powders where characterised in terms of yield, particle
      size (PS), residual solvent content (RSC) and outlet temperature. An additional
      outcome evaluated was the specific surface area (SSA) (by BET gas adsorption),
      and a relation between SSA and the in vitro deposition of the sugar NPMPs powders
      was also investigated. The DOE resulted in well fitted models. The most
      significant factors affecting the characteristics of the NPMPs prepared, at a 95%
      confidence interval, were gas flow: yield, PS and SSA; pump setting: yield; inlet
      temperature: RSC. Raffinose NPMPs presented better characteristics than trehalose
      NPMPs in terms of their use for inhalation, since particles with larger surface
      area resulting in higher fine particle fraction can be produced.

PMID- 21963474
TI  - Development of lysolipid-based thermosensitive liposomes for delivery of high
      molecular weight proteins.
AB  - The purpose of the present investigation was to determine the feasibility of
      using lysolipid-based thermal sensitive liposomes (145nm) for high molecular
      weight molecule delivery. Fluorescein isothiocyanate conjugate-albumin was used
      as a model drug (MW 66kDa). Thermal sensitive liposomes, which encapsulated the
      protein were prepared using a passive encapsulation methodology involving freeze
      thawing cycles followed by extrusion. In vitro release studies at various
      temperatures indicated rapid release behaviour of the encapsulated protein at 42
      and 44.5 degrees C but a good stability at 37.5 degrees C. The current findings
      suggest that lysolipid-based thermal sensitive liposomes can be used to deliver
      high molecular weight molecules.

PMID- 21963475
TI  - Evaluating the link between self-assembled mesophase structure and drug release.
AB  - Lipid-based liquid crystalline materials are of increasing interest for use as
      drug delivery systems. The intricate nanostructure of the reversed bicontinuous
      cubic (V(2)) and inverse hexagonal (H(2)) liquid crystal matrices have been shown
      to provide diffusion controlled release of actives of varying size and polarity.
      In this study, we extend the understanding of release to other self-assembled
      phases, the micellar cubic phase (I(2)) and inverse micelles (L(2)). The systems
      are comparable as they were all prepared from the one lipid, glyceryl monooleate
      (GMO), which sequentially forms all four phases with increasing hexadecane (HD)
      content in excess water. Phase identity was confirmed by small angle X-ray
      scattering (SAXS). SAXS data indicated that four mesophases were formed with
      increasing HD content at 25 degrees C: V(2) phase (Pn3m space group) formed at 0
      4% (w/w) HD, H(2) phase formed at 4-25% (w/w) HD, I(2) phase (Fd3m space group)
      formed at 25-40% (w/w) HD and finally L(2) phase formed at >40% (w/w) HD.
      Analogous compositions using phytantriol rather than GMO as the core lipid did
      not produce the I(2) phase, with only V(2) to H(2) to L(2) transitions being
      apparent with increasing HD concentration. In order to relate the liquid crystal
      phase structure to drug release rate, in vitro release tests were conducted by
      incorporating radio-labelled glucose as a model hydrophilic drug into the four
      GMO-based mesophases. It was found that the drug release followed first-order
      diffusion kinetics and was fastest from V(2) followed by L(2), H(2), and I(2).
      Drug release was shown to be significantly faster from bicontinuous cubic phase
      than the other mesophases, indicating that the state of the water compartments,
      whether open or closed, has a great influence on the rate of drug release. It is
      envisioned that liquid crystalline mesophases with slower release characteristics
      will more likely have potential applications as sustained release drug delivery
      systems, and hence that the bicontinuous cubic phase is not necessarily the best
      choice for a sustained release matrix.

PMID- 21963476
TI  - Doxazosin-carrageenan interactions: a novel approach for studying drug-polymer
      interactions and relation to controlled drug release.
AB  - When a cationic drug like doxazosin mesylate (DM) is incorporated into matrix
      tablets made of anionic polyelectrolytes carrageenans (CARRs) of different types
      (kappa-, iota-, lambda-CARR), DM-CARR interactions have a strong impact on drug
      release. To investigate these interactions, special DM ion-selective membrane
      electrode was made and applied for construction of binding isotherms. Isotherms
      were treated by the Zimm-Bragg theory and cooperative binding model. It was
      demonstrated that binding of doxazosin cations, DH(+), to CARRs is cooperative.
      It starts at very low drug concentrations with strong electrostatic interactions
      followed by aggregation of DH(+) ions. Hydrophobic interactions between bound
      DH(+) substantially contribute to the extent of binding. The strength of
      interactions increases with increasing negative charge of CARRs. At saturation,
      the number of DM molecules bound per repeat unit depends on the charge and steric
      distribution of binding sites on CARRs. Drug release rates of DM from CARR
      matrices were in accordance with the cooperativity binding constants: the weakest
      binding resulted in the fastest release. However it was proven that prolonged
      drug release is possible only by several processes running simultaneously, i.e.,
      by swelling and erosion of CARR matrices on one side and electrostatic
      interactions and cooperativity effects on the other.

PMID- 21963477
TI  - Exploratory study of proteins in urine of patients with histoplasma antigenuria.
AB  - Disseminated histoplasmosis is an invasive fungal infection that can be fatal in
      patients with weak immune system. The goal of our exploratory study was to
      evaluate differences in urinary protein profiles among samples of healthy
      individuals, patients with proteinuria (PRU), and histoplasma antigenuria (HIS),
      and to identify physiological pathways associated with the excreted proteins.
      Urine samples were depleted of abundant proteins, deglycosylated, digested with
      trypsin, fractionated and analyzed by nano-LC-QTOF. The total number of human
      proteins identified in the samples was 117, of which 20 and 23 were unique to the
      samples from patients with PRU and HIS, respectively. Pathway analysis of
      proteins identified in samples of PRU and HIS patients suggested increased levels
      of proteins associated with acute response signaling, coagulation system,
      prothrombin activation, glucocorticoid regulation and the lipid antigen
      presentation signaling pathway networks. The obtained data provide information on
      protein expression associated with HIS, and suggest that further more rigorous
      studies aimed at the identification of proteins associated with proteinuria of
      different causes are feasible.

PMID- 21963478
TI  - Determination of organophosphorus pesticides in peanut oil by dispersive solid
      phase extraction gas chromatography-mass spectrometry.
AB  - The organophosphorus pesticides including phorate, diazinon, tolclofos-methyl,
      fenitrothin, malathion, fenthion, isocarbophos, quinalphos and phenamiphos, in
      peanut oils were determined by liquid-liquid extraction coupled with dispersive
      solid phase extraction and gas chromatography-mass spectrometry (GC-MS). The
      mixture of multi-walled carbon nanotubes and alumina was used as adsorbent in
      dispersive solid phase extraction. The effects of some experimental conditions,
      such as types of multi-walled carbon nanotubes, amount of adsorbents and
      extraction time were examined. The limits of detection for the analytes were
      between 0.7 and 1.6 MUg kg(-1). The obtained recoveries of the analytes in the
      samples were between 85.9 and 114.3% and relative standard deviations were lower
      than 8.48%.

PMID- 21963479
TI  - Simultaneous determination of timolol maleate, rosuvastatin calcium and
      diclofenac sodium in pharmaceuticals and physiological fluids using HPLC-UV.
AB  - A novel HPLC-UV method was developed for the simultaneous determination of
      timolol (TM), rosuvastatin (RST), and diclofenac sodium (DS) in pharmaceuticals,
      human plasma and aqueous humor using naproxen sodium as internal standard (IS).
      The target compounds were analyzed on Hypersil BDS C(18) column (250 mm * 4.6 mm,
      5 MUm), applying 0.2% triethylamine (TEA) and acetonitrile (ACN) (40:60, v/v), in
      isocratic mode as mobile phase, pH 2.75 adjusted with 85% phosphoric acid at a
      flow rate of 1 ml/min. The column oven temperature was kept at 45 degrees C and
      the peak response was monitored at 284 nm after injecting a 50 MUl sample into
      HPLC system. The direct liquid-liquid extraction procedure was applied to human
      plasma and bovine aqueous humor samples using mobile phase as an extraction
      solvent after deproteination with methanol. The different HPLC experimental
      parameters were optimized and the method was validated according to standard
      guidelines. The recoveries of the suggested method in human plasma were 98.72,
      96.04, and 95.14%, for TM, RST, and DS, while in aqueous humor were 94.99, and
      98.23%, for TM, and DS, respectively. The LOD values were found to be 0.800,
      0.500, and 0.250 ng/ml, for TM, RST, and DS, respectively, while their respective
      LOQ values were 2.00, 1.50, and 1.00 ng/ml. The co-efficient of variation (CV)
      were in the range of 0.1492-1.1729% and 1.0516-4.0104%, for intra-day and inter
      day studies, respectively. The method was found accurate in human plasma and
      bovine aqueous humor and will be applied for the quantification of these
      compounds in plasma, and aqueous humor samples using animal models and in
      pharmaceuticals.

PMID- 21963480
TI  - Reversed phase liquid chromatography method with fluorescence detection of
      gemifloxacin in rat plasma and its application to the pharmacokinetic study.
AB  - A simple, accurate and precise high-performance liquid chromatographic method
      with fluorescence detection was developed and validated for the determination of
      gemifloxacin (GEM) in rat plasma using furosemide as internal standard (I.S.).
      Plasma samples were pretreated by direct deproteinization and all samples and
      standard solutions were chromatographed at 45 degrees C using triethylamine
      solution (0.5%, v/v, pH 3.0+/-0.1), methanol and acetonitrile (63:30:7, v/v/v) as
      the mobile phase. Chromatographic resolution was achieved using a RP-C(18) column
      (Atlantis, Waters, 150 mm * 4.6 mm, 5 MUm) at a flow rate of 1.0 mL min(-1) and
      an injection volume of 30 MUL. The analytes were measured by fluorescence
      detection with excitation and emission wavelengths of 344 nm and 399 nm,
      respectively. The retention times for GEM and I.S. were approximately 7.5 and
      12.6 min, respectively. The lower limit of quantitation (LLOQ) was 20 ng mL(-1)
      and the calibration curves were linear over a concentration range of 20-5000 ng
      mL(-1). The intra- and inter-day precisions, expressed by relative standard
      deviation (R.S.D.) were lower than 6.24% and 4.49%, respectively. The accuracy
      ranged from 91.3% to 112% and from 98.8% to 106% for the lower and upper limit of
      quantitation of the calibration curve, respectively. Ratio of peak area of
      analyte to I.S. was used for quantification of plasma samples. No interferences
      from endogenous substances were found. The recovery of GEM and I.S. from plasma
      was greater than 90%. Drug stability in plasma was shown at room temperature for
      4h, after three freeze-thaw cycles for 24h, in freezer at -80 degrees C for 60
      days, and in the autosampler after processing for 12h. The utility of the assay
      was confirmed by the successful analysis of plasma samples from GEM
      pharmacokinetics studies in the rats after intravenous administration.

PMID- 21963481
TI  - Quantification of intracellular and extracellular prostanoids stimulated by
      A23187 by liquid chromatography/electrospray ionization tandem mass spectrometry.
AB  - Prostanoids are bioactive substances that contribute to various biological and
      pathological processes. To evaluate both extracellular and intracellular levels
      of prostanoids at the same time, we developed methods for quantification of
      extracellular and intracellular levels of prostanoids, including prostaglandin
      E(2) (PGE(2)), PGD(2), PGF(2alpha), 6-keto PGF(1alpha), and TXB(2), in cultured
      cells using liquid chromatography/tandem mass spectrometry (LC/MS/MS), and we
      validated the LC/MS/MS methods. A solid-phase extraction cartridge was used for
      extraction of prostanoids. The prostanoids were separated by a C(18) column with
      an isocratic flow of acetonitrile/water/acetic acid (40:60:0.1, v/v/v).
      Calibration curves of extracellular measurement for the prostanoids were linear
      in the range from 0.1 to 100 ng/mL (r(2)>0.999), and those of intracellular
      measurement were linear in the range from 0.05 to 50 ng (r(2)>0.999). Validation
      assessment showed that both methods of extracellular and intracellular
      measurements were highly reliable with good accuracy and precision. We also
      applied the methods to human airway epithelial Calu-3 cells and human lung
      adenocarcinoma epithelial A549 cells.

PMID- 21963482
TI  - Quantitative subproteomic analysis of age-related changes in mouse liver
      peroxisomes by iTRAQ LC-MS/MS.
AB  - Aging is a complex multifactorial phenomenon, which is believed to result from
      the accumulation of cellular damage to biological macromolecules. Peroxisomes
      recently emerged as another important source of reactive oxygen species (ROS)
      production in addition to mitochondria. However, the role of these organelles in
      the process of aging is still not clear. The aim of this study was to
      characterize the changes in protein expression profiles of young (10 weeks old)
      versus old (18 months old) mouse liver peroxisome-enriched fractions. We have
      applied shotgun proteomic approach based on liquid chromatography and tandem mass
      spectrometry (LC-MS/MS) combined with iTRAQ (isobaric tags for relative and
      absolute quantitation) labeling that allows comparative quantitative multiplex
      analysis. Our analysis led to identification and quantification of 150 proteins,
      8 out of which were differentially expressed between two age groups at a
      statistically significant level (p<0.05), with folds ranging from 1.2 to 4.1.
      These proteins involved in peroxisomal beta-oxidation, detoxification of
      xenobiotics and production of ROS. Noteworthy, differences in liver proteome have
      been observed between as well as within different age groups. In conclusion, our
      subproteomic quantitative study suggests that mouse liver proteome is
      sufficiently maintained until certain age.

PMID- 21963483
TI  - Simultaneous quantification of nicotine and metabolites in rat brain by liquid
      chromatography-tandem mass spectrometry.
AB  - A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for
      simultaneous quantification of nicotine (NIC), cotinine (COT), nornicotine
      (NNIC), norcotinine (NCOT), nicotine-N-beta-D-glucuronide (NIC GLUC), cotinine-N
      beta-D-glucuronide (COT GLUC), nicotine-1'-oxide (NNO), cotinine-N-oxide (CNO),
      trans-3'-hydroxycotinine (3-HC), anabasine (AB) and anatabine (AT) was modified
      and validated for quantification of these selected analytes in rat brain tissue.
      This analytical method provides support for preclinical NIC pharmacokinetic and
      toxicological studies after controlled dosing protocols. After brain
      homogenization and solid-phase extraction, target analytes and corresponding
      deuterated internal standards were chromatographically separated on a
      Discovery((r)) HS F5 HPLC column with gradient elution and analyzed by LC-MS/MS
      in positive electrospray ionization (ESI) mode with multiple reaction monitoring
      (MRM) data acquisition. Method linearity was assessed and calibration curves were
      determined over the following ranges: 0.1-7.5 ng/mg for NIC, COT GLUC and AB; and
      0.025-7.5 ng/mg for COT, NNIC, NCOT, NIC GLUC, NNO, CNO, 3-HC and AT (R(2)>=0.99
      for all analytes). Extraction recoveries ranged from 64% to 115%, LC-MS/MS matrix
      effects were <=21%, and overall process efficiency ranged from 57% to 93% at low
      and high quality control concentrations. Intra- and inter-assay imprecisions and
      accuracy for all analytes were <=12.9% and >=86%, respectively. The method was
      successfully applied to quantification of NIC and metabolites in the brain of
      post-natal day 90 rats that were sacrificed 2-h after a single 0.8 mg/kg s.c.
      administration of (-)NIC. In these tissues, striatal concentrations were 204.8+/
      49.4, 138.2+/-14.2 and 36.1+/-6.1 pg/mg of NIC, COT and NNIC, respectively.
      Concentrations of NIC, COT and NNIC in the remaining whole brain (RWhB) were
      183.3+/-68.0, 130.0+/-14.1 and 46.7+/-10.3 pg/mg, respectively. Quantification of
      these same analytes in plasma was also performed by a previously validated
      method. NIC, COT, NNIC, NCOT, NNO and CNO were detected in plasma with
      concentrations comparable to those reported in previous studies. However, and in
      contrast to brain tissues, COT concentrations in plasma were significantly higher
      than were those of NIC (194.6+/-18.6 ng/mL versus 52.7+/-12.9 ng/mL). Taken
      together, these results demonstrate that a sensitive and selective method has
      been developed for the determination of NIC biomarkers in rat brain.

PMID- 21963484
TI  - Engineering topology and kinetics of sucrose metabolism in Saccharomyces
      cerevisiae for improved ethanol yield.
AB  - Sucrose is a major carbon source for industrial bioethanol production by
      Saccharomyces cerevisiae. In yeasts, two modes of sucrose metabolism occur: (i)
      extracellular hydrolysis by invertase, followed by uptake and metabolism of
      glucose and fructose, and (ii) uptake via sucrose-proton symport followed by
      intracellular hydrolysis and metabolism. Although alternative start codons in the
      SUC2 gene enable synthesis of extracellular and intracellular invertase isoforms,
      sucrose hydrolysis in S. cerevisiae predominantly occurs extracellularly. In
      anaerobic cultures, intracellular hydrolysis theoretically enables a 9% higher
      ethanol yield than extracellular hydrolysis, due to energy costs of sucrose
      proton symport. This prediction was tested by engineering the promoter and 5'
      coding sequences of SUC2, resulting in predominant (94%) cytosolic localization
      of invertase. In anaerobic sucrose-limited chemostats, this iSUC2-strain showed
      an only 4% increased ethanol yield and high residual sucrose concentrations
      indicated suboptimal sucrose-transport kinetics. To improve sucrose-uptake
      affinity, it was subjected to 90 generations of laboratory evolution in
      anaerobic, sucrose-limited chemostat cultivation, resulting in a 20-fold decrease
      of residual sucrose concentrations and a 10-fold increase of the sucrose
      transport capacity. A single-cell isolate showed an 11% higher ethanol yield on
      sucrose in chemostat cultures than an isogenic SUC2 reference strain, while
      transcriptome analysis revealed elevated expression of AGT1, encoding a
      disaccharide-proton symporter, and other maltose-related genes. After deletion of
      both copies of the duplicated AGT1, growth characteristics reverted to that of
      the unevolved SUC2 and iSUC2 strains. This study demonstrates that engineering
      the topology of sucrose metabolism is an attractive strategy to improve ethanol
      yields in industrial processes.

PMID- 21963485
TI  - Facile production of minor metabolites for drug development using a CYP3A
      shuffled library.
AB  - Metabolic profiling of new drugs is limited by the difficulty in obtaining
      sufficient quantities of minor metabolites for definitive structural
      identification. Biocatalytic methods offer the potential to produce metabolites
      that are difficult to synthesize by traditional medicinal chemistry. We
      hypothesized that the regioselectivity of the drug metabolizing cytochrome P450s
      could be altered by directed evolution to produce minor metabolites of drugs in
      development. A biocatalyst library was constructed by DNA shuffling of four CYP3A
      forms. The library contained 11 +/- 4 (mean +/- SD) recombinations and 1 +/- 1
      spontaneous mutations per mutant. On expression in Escherichia coli, 96% of
      mutants showed detectable activity to at least one probe substrate. Using
      testosterone as a model drug-like substrate, mutants were found that
      preferentially formed metabolites produced in only trace amounts by parental
      forms. A single 1.6L batch culture of one such mutant enabled the facile
      isolation of 0.3mg of the minor metabolite 1beta-hydroxytestosterone and its ab
      initio structural determination by 1D- and 2D-NMR spectroscopy.

PMID- 21963486
TI  - Spectral-domain optical coherence tomography in Irvine-Gass syndrome.
AB  - PURPOSE: To report longitudinal evaluation of morphology and function, by
      spectral-domain optical coherence tomography and Early Treatment Diabetic
      Retinopathy Study visual acuity, respectively, in patients with cystoid macular
      edema after cataract surgery (Irvine-Gass syndrome). METHODS: Fifteen eyes (15
      patients) with a diagnosis of cystoid macular edema related to Irvine-Gass
      syndrome underwent ocular ophthalmologic examinations including Early Treatment
      Diabetic Retinopathy Study visual acuity and macular morphology assessment by
      spectral-domain optical coherence tomography. An observational period of 3 months
      after surgery was considered before starting therapy with oral acetazolamide and
      topical indomethacin. Patients' eyes were tested at baseline and at 3, 6, and 12
      months posttreatment by spectral-domain optical coherence tomography and Early
      Treatment Diabetic Retinopathy Study visual acuity. Repeated measures analysis of
      variance was used to compare mean values. RESULTS: Mean (+/-SD) central macular
      thickness by spectral-domain optical coherence tomography was 530 (+/-98.1),
      385.6 (+/-55.1), 339 (+/-32.3), and 316.2 (+/-27.0) MUm at baseline, 3, 6, and 12
      months of follow-up, respectively (P < 0.001). Mean (+/-SD) Early Treatment
      Diabetic Retinopathy Study visual acuity was 0.6 (+/-0.2), 0.2 (+/-0.1), 0.16 (+/
      0.1), and 0.09 (+/-0.07) logarithm of the minimum angle of resolution at
      baseline, 3, 6, and 12-month follow-up, respectively (P < 0.001). Macular
      thickness changes were positively correlated (r = 0.75; P < 0.001) with visual
      acuity changes. Eyes with interruption of inner segment/outer segment junction at
      baseline (n = 3, 20%) showed a persistent damage of the photoreceptor junction
      and incomplete visual acuity recovery at the end of follow-up. CONCLUSION:
      Spectral-domain optical coherence tomography detects retinal findings, including
      photoreceptor inner segment/outer segment junction abnormalities that are
      correlated with visual acuity changes in treated patients with Irvine-Gass
      syndrome.

PMID- 21963487
TI  - Treatment of intractable posterior uveitis in pediatric patients with the
      fluocinolone acetonide intravitreal implant (Retisert).
AB  - PURPOSE: To evaluate the efficacy and safety of the fluocinolone acetonide
      intravitreal implant in pediatric patients with intractable noninfectious
      posterior uveitis. METHODS: A retrospective chart review was performed on all
      patients aged <18 years on whom a fluocinolone implant was used to treat
      intractable posterior uveitis at our institution. Conventional treatment with
      topical and systemic steroids and/or systemic steroid-sparing agents failed in
      all patients before proceeding with an implant. Each implant contained 0.59 mg of
      fluocinolone acetonide. Implants were placed in the inferonasal quadrant through
      a pars plana incision and sutured in place with 8-0 proline suture.
      Postoperatively, patients were followed for improvement in Snellen visual acuity,
      control of inflammation, and development of complications such as infection or
      uncontrolled intraocular pressure in the eyes. RESULTS: The study included six
      eyes of four patients. Mean age at implant placement was 9.2 years (range, 6-13
      years). Four eyes were pseudophakic at the time of surgery; one eye had pars
      plana lensectomy at the time of surgery. Mean follow-up duration was 698 days
      (range, 376-1,189 days). Postoperative visual acuity improved by >=3 lines in 3
      eyes. Four eyes had postoperative intraocular spikes >=30 mmHg, with 2 eyes
      having >=40 mmHg. Two of these patients required glaucoma shunting procedures
      postoperatively for intraocular pressure control. Inflammation was well
      controlled postoperatively in all six eyes with all eyes successfully weaned off
      of topical steroids. The single phakic eye developed a visually significant
      cataract 18 months postoperatively requiring cataract extraction. There were no
      cases of postoperative infection. There were no postoperative complications of
      surgical technique including no instances of wound leakage or implant
      dislocation. CONCLUSION: The fluocinolone implant can be used effectively for
      control of posterior inflammation in pediatric patients. As in adults, concerns
      for development of cataract and secondary glaucoma remain. No other safety
      concerns were evident in this pilot study.

PMID- 21963488
TI  - Experimental improvements in combining CARD-FISH and flow cytometry for bacterial
      cell quantification.
AB  - Flow cytometry and Fluorescence In Situ Hybridization are common methods of
      identifying and quantifying bacterial cells. The combination of cytometric
      rapidity and multi-parametric accuracy with the phylogenetic specificity of
      oligonucleotide FISH probes has been regarded as a powerful and emerging tool in
      aquatic microbiology. In the present work, tests were carried out on E. coli pure
      culture and marine bacteria using an in-solution hybridization protocol revealing
      high efficiency hybridization signal for the first one and a lower for the second
      one. Other experiments were conducted on natural samples following the
      established CARD-FISH protocol on filter performed in a closed system, with the
      aim of improving cell detachment and detection. The hybridized cells were then
      subsequently re-suspended from the membrane filters by means of an optimized
      detachment procedure. The cytometric enumeration of hybridized marine bacteria
      reached 85.7%+/-18.1% of total events. The quality of the cytograms suggests that
      the procedures described may be applicable to the cytometric quantification of
      phylogenetic groups within natural microbial communities.

PMID- 21963489
TI  - Molecular pathogen detection in biosolids with a focus on quantitative PCR using
      propidium monoazide for viable cell enumeration.
AB  - Sewage sludge is the solid, organic material remaining after wastewater is
      treated and discharged from a wastewater treatment plant. Sludge is treated to
      stabilize the organic matter and reduce the amount of human pathogens. Once
      government regulations are met, including material quality standards (e.g., E.
      coli levels and heavy metal content) sludge is termed "biosolids", which may be
      disposed of by land application according to regulations. Live-culture techniques
      have traditionally been used to enumerate select pathogens and/or indicator
      organisms to demonstrate compliance with regulatory requirements. However, these
      methods may result in underestimates of viable microorganisms due to several
      problems, including their inability to detect viable but non-culturable (VBNC)
      cells. Real-time quantitative polymerase chain reaction (qPCR) is currently under
      investigation as a fast, sensitive, and specific molecular tool for enumeration
      of pathogens in biosolids. Its main limitation is that it amplifies all target
      DNAs, including that from non-viable cells. This can be overcome by coupling qPCR
      with propidium monoazide (PMA), a microbial membrane-impermeant dye that binds to
      extracellular DNA and DNA in dead or membrane-compromised cells, inhibiting its
      amplification. PMA has successfully been used to monitor the presence of viable
      pathogens in several different matrices. In this review the use of PMA-qPCR is
      discussed as a suitable approach for viable microbial enumeration in biosolids.
      Recommendations for optimization of the method are made, with a focus on DNA
      extraction, dilution of sample turbidity, reagent concentration, and light
      exposure time.

PMID- 21963490
TI  - Electrocardiographic and biochemical evidence for the cardioprotective effect of
      antioxidants in acute doxorubicin-induced cardiotoxicity in the beagle dogs.
AB  - Doxorubicin (DOX) is a potent antitumor agent, but the cardiotoxicity mediated by
      the formation of reactive oxygen species limit its clinical use. The present
      study aims to explore electrocardiographic and biochemical evidence for the
      cardioprotective effect of two antioxidants, Lycium barbarum polysaccharides
      (LBP, the main antioxidant in Lycium barbarum) and edaravone (a potent free
      radical scavenger, EDA) against DOX-induced acute cardiotoxicity in beagle dogs.
      In this study, male beagle dogs received daily treatment of either LBP (20 mg/kg,
      per os (p.o.)) or EDA (2 mg/kg, intravenously (i.v.)) for 7 d and then followed
      by an intravenous injection of DOX (1.5 mg/kg). DOX (15 mg/kg) significantly
      induced acute cardiotoxicity in dogs characterized by conduction abnormalities
      (including decreased heart rate, ST segment elevation, QT intervals prolongation,
      inverted T wave, arrhythmia, and myocardial ischemia) and increased serum
      creatine kinase (CK) and aspartate aminotransferase (AST). Pretreatment with LBP
      or EDA effectively alleviated both DOX-associated conduction abnormalities and
      increased serum CK and AST. Moreover, physiological and serum biochemical
      evidences demonstrated that EDA is more effective than LBP in alleviating these
      abnormalities produced by DOX in heart. All these results confirm and extend
      previous observations in rats concerning the effectiveness of LBP or EDA against
      DOX-induced cardiomyopathy.

PMID- 21963491
TI  - Galphaq-protein carboxyl terminus imitation polypeptide GCIP-27 attenuates
      proliferation of vascular smooth muscle cells and vascular remodeling in
      spontaneously hypertensive rats.
AB  - Gq-protein is located at the convergent point in signal transduction pathways
      leading to vascular remodeling. The carboxyl terminus of Galpha-subunit plays a
      vital role in G-protein-receptor interaction. The present study was designed to
      explore the effects of a synthetic Galphaq carboxyl terminus imitation peptide,
      namely GCIP-27, on vascular smooth muscle cells (VSMC) in vitro and vascular
      remodeling in spontaneous hypertensive rats (SHR). Hyperplasia and hypertrophy of
      VSMC wre determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) assay, [(3)H]-thymidine and [(3)H]-leucine incorporation, and
      [Ca(2+)](i) was measured with Fluo-3/AM staining. Systolic blood pressure (SBP),
      the ratio of media thickness to lumen diameter (MT/LD) of aorta, collagen
      content, and phospholipase C activity in aorta were measured in SHR. GCIP-27 (3
      100 ug/l) significantly decreased proliferation activity, protein content,
      incorporation of [(3)H]-thymidine and [(3)H]-leucine, and [Ca(2+)](i) level in
      VSMC. SBP, MT/LD, collagen content, and phospholipase C activity in aorta of SHR
      were decreased significantly in GCIP-27 (7, 20, 60 ug/kg)-treated groups and
      losartan (6 mg/kg) group compared with vehicle group. In conclusion, GCIP-27
      could inhibit vascular remodeling effectively in vitro and in vivo.

PMID- 21963492
TI  - Mast cell development and biostresses: different stromal responses in bone marrow
      and spleen after treatment of myeloablater, 5-fluorouracil, and inflammatory
      stressor, lipopolysaccharide.
AB  - Mast-cell-development in the bone-marrow (BM) and the spleen is restrictedly
      controlled by stromal-cells which produce positive-regulators such as stem cell
      factor (SCF), and negative-regulators such as transforming growth factor-beta
      (TGF-beta). How the balance between positive- and negative-regulation is achieved
      or maintained by stromal-cells is not well understood. We intravenously injected
      5-fluorouracil (5-FU) and lipopolysaccharide (LPS) into C3H/HeN mice to disrupt
      mast-cell-development in order to reveal mechanisms of mast-cell-regulation. 5-FU
      treatment induces a rapid decrease in the number of mast-cell-progenitor (colony
      forming unit (CFU)-mast) cells in the BM and spleen, followed by rapid recovery
      of CFU-mast numbers. Expression of the SCF gene is one-fiftieth the level of that
      of TGF-beta during the steady-state in BM and spleen. After 5-FU treatment, SCF
      mRNA levels in the BM markedly increased, approaching TGF-beta mRNA levels,
      whereas SCF levels in the spleen showed limited oscillations whose increases
      paralleled those in TGF-beta levels. In contrast, LPS treatment induces a rapid
      decrease in CFU-mast number in the BM and a rapid increase in of CFU-mast number
      in the spleen. After LPS treatment, SCF mRNA levels in the BM markedly decreased,
      whereas SCF levels in the spleen remained unchanged. These results suggest that
      regulation of mast-cell-development is dominated by negative-signals in the BM
      and spleen during the steady-state, and, under biostress-conditions such as 5-FU
      and LPS treatment, the balance between positive- and negative-regulation can be
      changed in the BM but not in the spleen. The difference in the regulation of mast
      cell-development in the BM versus the spleen probably reflects the different
      roles of tissue-specific stromal-cells.

PMID- 21963493
TI  - Activation of extracellular-signal regulated kinase by epidermal growth factor is
      potentiated by cAMP-elevating agents in primary cultures of adult rat
      hepatocytes.
AB  - We investigated the effects of alpha- and beta-adrenergic agonists on epidermal
      growth factor (EGF)-stimulated extracellular-signal regulated kinase (ERK)
      isoforms in primary cultures of adult rat hepatocytes. Hepatocytes were isolated
      and cultured with EGF (20 ng/ml) and/or alpha(1)-, alpha(2)- and beta(2)
      adrenergic agonists. Phosphorylated ERK isoforms (ERK1; p44 mitogen-activated
      protein kinase (MAPK) and ERK2; p42 MAPK) were detected by Western blotting
      analysis using anti-phospho-ERK1/2 antibody. The results show that EGF induced a
      2.5-fold increase in ERK2-, but not ERK1-, phosphorylation within 3 min. This EGF
      induced ERK2 activation was abolished by treatment with the EGF-receptor kinase
      inhibitor AG1478 (10(-7) M) or the MEK (MAPK kinase) inhibitor PD98059 (10(-6)
      M). The alpha(2)-adrenergic and beta(2)-adrenergic agonists, UK14304 (10(-6) M)
      and metaproterenol (10(-6) M), respectively, had no effect in the absence of EGF,
      but metaproterenol significantly potentiated EGF-induced ERK2 phosphorylation.
      Moreover, the cell-permeable cAMP analog 8-bromo cAMP (10(-7) M), also
      potentiated EGF-induced ERK2 phosphorylation. The effects of these analogs were
      antagonized by the protein kinase A (PKA) inhibitor H-89 (10(-7) M). These
      results suggest that direct or indirect activation of PKA represents a positive
      regulatory mechanism for EGF stimulation of ERK2 induction.

PMID- 21963494
TI  - Aglycon of rhizochalin from the Rhizochalina incrustata induces apoptosis via
      activation of AMP-activated protein kinase in HT-29 colon cancer cells.
AB  - Rhizochalin is a two-headed sphingolipid-like compound isolated from the sponge
      Rhizochalina incrustata. It has been reported that rhizocalin and its derivates
      have a chemopreventive and chemotherapeutic effect. However, the molecular
      mechanism of these effects is not understood. Here, we demonstrate that aglycon
      of rhizochalin (AglRhz) from the Rhizochalina incrustata induces AMP-activated
      protein kinase (AMPK) phosphorylation, and thereby inhibits mammalian target of
      rapamycin (mTOR)-p70S6 kinase-extracellular signal-regulated kinase (ERK)
      signaling and activator protein 1 (AP-1) activity via phosphorylation of Raptor
      in HT-29 cells. In addition, AglRhz induced activation of caspase-3 and poly(ADP
      ribose) polymerase (PARP), and DNA fragmentation in HT-29 cells, leads to
      induction of apoptosis as well as suppression of tumorigenicity of HT-29 cells.
      Notably, AglRhz inhibits insulin-like growth factor (IGF)-1-induced AP-1 activity
      and cell transformation in JB6 Cl41 cells. Overall, our findings identify AMPK as
      an important target protein for mediating the anti-tumor properties of AglRhz in
      HT-29 colon cancer cells and have important implication for sponges, the most
      important marine source, in colon cancer.

PMID- 21963495
TI  - Evaluation of morroniside, iridoid glycoside from Corni Fructus, on diabetes
      induced alterations such as oxidative stress, inflammation, and apoptosis in the
      liver of type 2 diabetic db/db mice.
AB  - The present study was conducted to examine whether morroniside has an
      ameliorative effect on diabetes-induced alterations such as oxidative stress,
      inflammation, and apoptosis in the liver of type 2 diabetic db/db mice.
      Morroniside (20 or 100 mg/kg body weight/d, per os (p.o.)) was administered every
      day for 8 weeks to db/db mice, and its effect was compared with vehicle-treated
      db/db and m/m mice. The administration of morroniside decreased the elevated
      serum glucose concentration in db/db mice, and reduced the increased oxidative
      biomarkers including the generation of reactive oxygen species and lipid
      peroxidation in the liver. The db/db mice exhibited the up-regulation of
      nicotinamide adenine dinucleotide phosphate oxidase subunits, NF-E2-related
      factor 2 (Nrf2), heme oxygenase-1, nuclear factor-kappa B, cyclooxygenase-2,
      inducible nitric oxide synthase, monocyte chemotactic protein-1, and
      intracellular adhesion molecule-1 levels in the liver; however, morroniside
      treatment significantly reduced those expressions. Moreover, the augmented
      expressions of apoptosis-related proteins, Bax and cytochrome c, were down
      regulated by morroniside administration. Hematoxylin-eosin staining showed that
      the increased hepatocellular damage in the liver of db/db mice improved on
      morroniside administration. Taking these into consideration, our findings support
      the therapeutic evidence for morroniside ameliorating the development of diabetic
      hepatic complications via regulating oxidative stress, inflammation, and
      apoptosis.

PMID- 21963496
TI  - Sauchinone suppresses pro-inflammatory mediators by inducing heme oxygenase-1 in
      RAW264.7 macrophages.
AB  - Sauchinone, a biologically active lignan isolated from the roots of Saururus
      chinensis (LOUR.) BAILL. (Saururaceae), is reported to exert a variety of
      biological activities, such as hepatoprotective, anti-inflammatory actions and
      inhibitory effects on bone resorption. In this study, we investigated the effect
      of sauchinone in suppressing cyclooxygenase-2 (COX-2) and inducible nitric oxide
      synthase (iNOS) expression, leading to a reduction in COX-2-derived prostaglandin
      E(2) (PGE(2)) and iNOS-derived nitric oxide (NO) production in lipopolysaccharide
      (LPS) stimulated RAW264.7 macrophages. Present study also demonstrates the
      effects of sauchinone in inducing heme oxygenase-1 (HO-1) expression and an
      increase in heme oxygenase (HO) activity in RAW264.7 macrophages. The effects of
      sauchinone on LPS-induced PGE(2), NO, tumor necrosis factor-alpha (TNF-alpha) and
      interlukine-1beta (IL-1beta) production were partially reversed by the HO-1
      inhibitor Tin protoporphyrin was also seen in this study. In addition, we found
      that treatment with extracellular signal-regulated kinase (ERK) inhibitor
      (PD98059) reduced sauchinone-induced HO-1 expression. Sauchinone also increased
      ERK phosphorylation. These results suggest that sauchinone inhibits pro
      inflammatory mediators through expression of anti-inflammatory HO-1 via ERK
      pathway.

PMID- 21963497
TI  - Development of a novel gene silencer pyrrole-imidazole polyamide targeting human
      connective tissue growth factor.
AB  - Pyrrole-imidazole (PI) polyamide can bind to specific sequences in the minor
      groove of double-helical DNA and inhibit transcription of the genes. We designed
      and synthesized a PI polyamide to target the human connective tissue growth
      factor (hCTGF) promoter region adjacent to the Smads binding site. Among coupling
      activators that yield PI polyamides, 1-[bis(dimethylamino)methylene]-5-chloro-1H
      benzotriazolium 3-oxide hexafluorophosphate (HCTU) was most effective in total
      yields of PI polyamides. A gel shift assay showed that a PI polyamide designed
      specifically for hCTGF (PI polyamide to hCTGF) bound the appropriate double
      stranded oligonucleotide. A fluorescein isothiocyanate (FITC)-conjugated PI
      polyamide to CTGF permeated cell membranes and accumulated in the nuclei of
      cultured human mesangial cells (HMCs) and remained there for 48 h. The PI
      polyamide to hCTGF significantly decreased phorbol 12-myristate acetate (PMA)- or
      transforming growth factor-beta1 (TGF-beta1)-stimulated luciferase activity of
      the hCTGF promoter in cultured HMCs. The PI polyamide to hCTGF significantly
      decreased PMA- or TGF-beta1-stimulated expression of hCTGF mRNA in a dose
      dependent manner. The PI polyamide to hCTGF significantly decreased PMA- or TGF
      beta1-stimulated levels of hCTGF protein in HMCs. These results indicate that the
      developed synthetic PI polyamide to hCTGF could be a novel gene silencer for
      fibrotic diseases.

PMID- 21963498
TI  - Steroid withdrawal based on lymphocyte sensitivity to endogenous steroid in renal
      transplant recipients.
AB  - Though steroid withdrawal is done in many renal transplant recipients, some
      patients must restart steroids. Little report has investigated steroid withdrawal
      under pharmacodynamic monitoring. We assessed lymphocyte sensitivity to
      endogenous cortisol as a biomarker for determining the safety of steroid
      withdrawal in renal transplant patients, as we hypothesized that patients
      hyposensitive to cortisol could not be sufficiently immunosuppressed by their
      intrinsic cortisol as a substitute for the reduced or withdrawn steroid.
      Lymphocyte sensitivity to cortisol was examined in 30 long stable renal
      transplant recipients. Lymphocyte sensitivity to cortisol and its relationship
      with the clinical outcome after steroid reduction and withdrawal was
      investigated. The lymphocyte sensitivities to cortisol were estimated as IC(50)
      of lymphocyte blastogenesis. The lymphocyte proliferation rate for concentration
      of serum cortisol compared between incident and non-incident groups. Serum
      creatinine levels (S-Cr) increased in a significantly higher number of patients
      hyposensitive to cortisol (IC(50)?10000 ng/ml) than in normally sensitive
      patients (IC(50)<10000 ng/ml). The incidences of steroid withdrawal syndrome and
      necessity for increasing steroid dose or restarting steroid administration were
      also higher in the patients hyposensitive to cortisol. The patients in whom the
      lymphocyte proliferation rate was less than 60% did not show increase in S-Cr,
      experience steroid withdrawal symptoms, or require an increase in the steroid
      dose or restart of steroid administration. The patients who have the normal
      IC(50) values of cortisol, can withdraw steroid more safely. The lymphocyte
      sensitivity to cortisol may be a useful biomarker for selecting patients who can
      sustain steroid withdrawal.

PMID- 21963499
TI  - Physalins A and B inhibit androgen-independent prostate cancer cell growth
      through activation of cell apoptosis and downregulation of androgen receptor
      expression.
AB  - Androgen deprivation therapy is a common treatment strategy for advanced prostate
      cancer. Though effective initially, the tumor often progresses to androgen
      independent stage in most patients eventually after a period of remission. One of
      the key factors of development of resistance is reflected in expression of
      androgen receptor (AR). In this study, we showed that two natural compounds,
      physalins A and B, both secosteriods from Physalisalkekengi var. franchetii,
      significantly inhibited the growth of two androgen-independent cell lines
      CWR22Rv1 and C42B, induced apoptosis via c-Jun N-terminal kinase (JNK) and/or
      extracellular signal-regulated kinase (ERK) activation, and decreased AR
      expression. In addition, physalins A and B down-regulated the expression of
      prostate specific antigen (PSA) in C42B cells which is a target gene of AR. Our
      results suggest that physalin A and B might be useful agents in preventing the
      growth of androgen-independent prostate cancer (AI-PCa).

PMID- 21963500
TI  - Overexpression of hematopoietically expressed homeoprotein induces nonapoptotic
      cell death in mouse prechondrogenic ATDC5 cells.
AB  - Physiological cell death is an essential event in normal development and
      maintenance of homeostasis. Recently, the morphological and pharmacological
      characteristics of programmed cell death, which are distinct from those of
      apoptosis under physiological and pathological conditions, have been reported.
      However, the molecular mechanism and executioner of this type of cell death are
      unknown. We show that overexpression of hematopoietically expressed homeoprotein
      (Hex), a homeoprotein of divergent type, and enhanced green fluorescent protein
      (EGFP) fusion protein (Hex-EGFP) induces cell death in mouse chondrogenic cell
      line ATDC5. The expression rate of Hex-EGFP decreased more rapidly than that of
      EGFP 96 h after transfection. The time-lapse image of living cells revealed the
      Hex-EGFP-positive cells rapidly died in a necrosis-like fashion. The nuclei of
      Hex-EGFP-expressing cells were rarely fragmented; however, these cells were
      negative for terminal deoxynucleotidyl transferase-mediated deoxyuridine
      triphosphate nick-end labeling (TUNEL) staining. The expression rate of Hex-EGFP
      clearly increased by treatment with radical scavengers, propyl gallate and
      butylated hydroxyanisole, slightly increased with a caspase inhibitor, zVAD-fmk,
      and was not affected by N-acetyl cysteine in ATDC5 cells. A fluorescent probe
      indicated that reactive oxygen species (ROS) were localized near the nuclei in
      Hex-EGFP-positive cells. In differentiated ATDC5 cells, as hypertrophic
      chondrocyte-like cells, the expression rate of Hex-EGFP increased above that in
      uninduced ATDC5 cells. These results suggest that Hex induces nonapoptotic cell
      death through local accumulation of reactive oxygen species, and mature
      chondrocytes, which express Hex, might be able to escape cell death induced by
      Hex in cartilage.

PMID- 21963501
TI  - Cardiovascular protection with danshensu in spontaneously hypertensive rats.
AB  - The objective of the present study was to evaluate the cardiovascular protective
      effects of Danshensu, a water-soluble active component of Danshen, in
      spontaneously hypertensive rats (SHR). SHR (male, 9 weeks old, n=30) were divided
      into three groups: 1) saline control (n=10); 2) a Danshensu (10 mg/kg/d,
      intraperitoneally (i.p.)) treatment group (n=10); and 3) a Valsartan (10 mg/kg/d,
      intragastrically (i.g.)) treatment group (n=10). Age-matched Wistar-Kyoto rats
      (n=10) were used as normotensive controls. Saline and drug treatments were
      administered for 6 weeks. When the rats were 15 weeks old, their hearts were
      excised and arrhythmias were induced by an ex vivo ischemia/reperfusion protocol.
      The heart weight to body weight index was significantly increased in SHR, and
      this increase was attenuated with Danshensu treatment (both p<0.05). Systolic
      blood pressure and diastolic blood pressure were also decreased with Danshensu
      treatment, from 145+/-3 and 103+/-10 mmHg to 116+/-7 and 87+/-2 mmHg in SHR and
      Danshensu-treated groups, respectively (both p<0.05). The incidences of
      ventricular tachycardia and ventricular fibrillation decreased from 100 to 50%
      and 30% in SHR, respectively, with Danshensu treatment (both p<0.05). Serum
      nitric oxide content and inducible nitric oxide synthase activity were
      significantly increased with Danshensu (both p<0.05). In addition, Danshensu
      increased the K(+) current density and Ca(2+) activated K(+) channel current
      density of mesenteric vascular smooth muscle cells isolated from SHRs. Together,
      these results demonstrate that Danshensu imparts cardiovascular protection by
      modifying vascular responses during the progression of hypertension.

PMID- 21963502
TI  - Indole-3-carbinol generates reactive oxygen species and induces apoptosis.
AB  - Cruciferous vegetables contain glucobrassicin which, during metabolism, yields
      indole-3-carbinol (I3C). The aim of this study was to find whether indole-3
      carbinol caused apoptosis and its mechanism in Candida albicans. We found that
      treatment of Candida albicans with indole-3-carbinol significantly increased the
      reactive oxygen species and hydroxyl radical accumulation. The hydroxyl radical
      is one of the most active components of oxygen, and it is the end product of an
      oxidative damage cellular death pathway. We investigated the general phenotypes
      of apoptosis and then investigated whether there were other distinct markers of
      apoptosis. Furthermore, the effects of thiourea as a hydroxyl radical scavenger
      and protective effect of trehalose, which is the result of the fungal immune
      system, was also assured. This study indicates that indole-3-carbinol has
      apoptosis effects, including a production of hydroxyl radicals, cytochrome c
      release and activation of metacaspase. Both hydroxyl radicals and metacaspases
      triggered apoptosis in Candida albicans.

PMID- 21963503
TI  - Effect of pharmacist management on serum hemoglobin levels with renal anemia in
      hemodialysis outpatients.
AB  - The initiation of a pharmacist-implemented management program to ensure
      appropriate use of erythropoietin-stimulating agents at Mizushima Kyodo Hospital
      is described. In the present study, we examined the influence of having
      pharmacists actively manage hemoglobin levels on therapeutic outcome in a
      retrospective study of 84 outpatients receiving hemodialysis. We compiled in
      hospital guidelines for the use of erythropoietin and iron for outpatients with
      renal anemia. Pharmacists made recommendations, particularly about changes in the
      dose of erythropoietin and administration of iron preparations, to physicians.
      Clinical test results were monitored for 12 months (between November 2007 and
      October 2008) with and without the participation of pharmacists (continuous 6
      months). The counseling by pharmacists significantly decreased hemoglobin levels
      in the high group (>12 g/dl) and significantly increased them in low group (<10
      g/dl). Furthermore, it increased hemoglobin levels in the optimal group,
      suggesting the management of our hospital guidelines. On the other hand, low
      levels of hemoglobin indicated low levels of albumin. It is suggested that no
      improvement in hemoglobin levels may indicate low levels of albumin. These
      findings suggest that the active participation of pharmacists in the management
      of renal anemia in hemodialysis patients had a great therapeutic impact.

PMID- 21963504
TI  - Preventive effect of geniposide on metabolic disease status in spontaneously
      obese type 2 diabetic mice and free fatty acid-treated HepG2 cells.
AB  - Accumulation of visceral fat induces various symptoms of metabolic syndrome such
      as insulin resistance and abnormal glucose/lipid metabolism and eventually leads
      to the onset of ischemic cerebrovascular diseases. Geniposide, which is iridoid
      glycoside from the fruit of Gardenia jasminoides ELLIS, is recognized as being
      useful against hyperlipidemia and fatty liver. In order to clarify the effect of
      geniposide on metabolic disease-based visceral fat accumulation and the relevant
      molecular mechanism, experiments were performed in spontaneously obese Type 2
      diabetic TSOD mice and the free fatty acid-treated HepG2 cells. In the TSOD mice,
      geniposide showed suppression of body weight and visceral fat accumulation,
      alleviation of abnormal lipid metabolism and suppression of intrahepatic lipid
      accumulation. In addition, geniposide alleviated abnormal glucose tolerance and
      hyperinsulinemia, suggesting that geniposide has an insulin resistance
      alleviating effect. Next, in order to investigate the direct effect of geniposide
      on the liver, the effect on the free fatty acid-treated HepG2 fatty liver model
      was investigated using genipin, which is the aglycone portion of geniposide.
      Genipin suppressed the intracellular lipid accumulation caused by the free fatty
      acid treatment and also significantly increased the intracellular expression of a
      fatty acid oxidation-related gene (peroxisomal proliferator-activated receptor:
      PPARalpha). From these results, it was confirmed that geniposide has an anti
      obesity effect, an insulin resistance-alleviating effect and an abnormal lipid
      metabolism-alleviating effect, and the metabolite genipin shows a direct effect
      on the liver, inducing expression of a lipid metabolism-related gene as one of
      its molecular mechanisms.

PMID- 21963505
TI  - Screening for microbial metabolites affecting phenotype of Caenorhabditis
      elegans.
AB  - Microbial samples, including our library of known microbial compounds (ca. 300)
      and microbial culture broths (ca. 9000), were screened for small molecules
      affecting the phenotype of Caenorhabditis elegans. As a result, seven known
      compounds were found to induce phenotypic abnormality of C. elegans.
      Staurosporine exhibited morphological defects in the vulva and tail of C.
      elegans, avermectin B1a exhibited hatching inhibition of starting eggs on day 1
      at 25-100 uM and growth inhibition at 0.01-12.5 uM, siccanin and antimycin A
      inhibited the growth of C. elegans, and fluorouracil inhibited hatching of eggs
      newly spawned by adult C. elegans. Toromycin induced morphological defects in the
      intestine. 5-(4-Methoxyphenyl)-oxazole, isolated as a fungal metabolite for the
      first time, inhibited the hatching of eggs newly spawned by adult C. elegans.

PMID- 21963506
TI  - Coffee induces breast cancer resistance protein expression in Caco-2 cells.
AB  - Coffee is a beverage that is consumed world-wide on a daily basis and is known to
      induce a series of metabolic and pharmacological effects, especially in the
      digestive tract. However, little is known concerning the effects of coffee on
      transporters in the gastrointestinal tract. To elucidate the effect of coffee on
      intestinal transporters, we investigated its effect on expression of the breast
      cancer resistance protein (BCRP/ABCG2) in a human colorectal cancer cell line,
      Caco-2. Coffee induced BCRP gene expression in Caco-2 cells in a coffee-dose
      dependent manner. Coffee treatment of Caco-2 cells also increased the level of
      BCRP protein, which corresponded to induction of gene expression, and also
      increased cellular efflux activity, as judged by Hoechst33342 accumulation. None
      of the major constituents of coffee tested could induce BCRP gene expression. The
      constituent of coffee that mediated this induction was extractable with ethyl
      acetate and was produced during the roasting process.
      Dehydromethylepoxyquinomicin (DHMEQ), an inhibitor of nuclear factor (NF)-kappaB,
      inhibited coffee-mediated induction of BCRP gene expression, suggesting
      involvement of NF-kappaB in this induction. Our data suggest that daily
      consumption of coffee might induce BCRP expression in the gastrointestinal tract
      and may affect the bioavailability of BCRP substrates.

PMID- 21963507
TI  - meso-Dihydroguaiaretic acid inhibits hepatic lipid accumulation by activating AMP
      activated protein kinase in human HepG2 cells.
AB  - Hepatic lipid accumulation is a major risk factor for dyslipidemia, nonalcoholic
      fatty liver disease, and insulin resistance. The present study was conducted to
      evaluate hypolipidemic effects of meso-dihydroguaiaretic acid (MDA), anti
      oxidative and anti-inflammatory compound isolated from the Myristica fragrans
      HOUTT., by oil red O staining, reverse transcription-polymerase chain reaction
      (RT-PCR), and Western blot. MDA significantly inhibited insulin-induced hepatic
      lipid accumulation in a dose-dependent manner. The lipid-lowering effect of MDA
      was accompanied by increased expression of proteins involved in fatty acid
      oxidation and decreased expression of lipid synthetic proteins. In addition, MDA
      activated AMP-activated protein kinase (AMPK) as determined by phosphorylation of
      acetyl-CoA carboxylase (ACC), a downstream target of AMPK. The effects of MDA on
      lipogenic protein expression were suppressed by pretreatment with compound C, an
      AMPK inhibitor. Taken together, these findings show that MDA inhibits insulin
      induced lipid accumulation in human HepG2 cells by suppressing expression of
      lipogenic proteins through AMPK signaling, suggesting a potent lipid-lowering
      agent.

PMID- 21963508
TI  - Two thiophenes compounds are partial peroxisome proliferator-activated receptor
      alpha/gamma dual agonists.
AB  - In our previous study, two synthetic thiophenes such as IMB-05 and IMB-15 were
      found as peroxisome proliferator-activated receptor gamma (PPARgamma) agonists
      and exhibited beneficial effects on glucose tolerance of diabetic mice in vivo.
      In the present study, their effect on the transactivity of other nuclear
      receptors was further investigated. IMB-05 and IMB-15 could not only activated
      PPARgamma but also efficiently activate PPARalpha in GAL4-hPPARalpha/gamma
      (ligand binding domain (LBD)) chimeric receptor assay and PPAR response element
      (PPRE)-luc reporter gene assay with EC(50) values of 1.8-5.2 uM, whereas no
      activity was observed in other nuclear receptor assays. In addition, the maximal
      efficacy of IMB-05 and IMB-15 in activating PPARalpha/gamma was approximately 30%
      of that observed with Wy14643 and rosiglitazone. These data indicate that the two
      thiophene derivatives are novel class of partial PPARalpha/gamma dual agonists,
      which may be the mechanism underlying their regulatory effects on glucose
      homeostasis.

PMID- 21963509
TI  - The DC2.3 gene in Caenorhabditis elegans encodes a galectin that recognizes the
      galactosebeta1->4fucose disaccharide unit.
AB  - Galectins comprise a large family of beta-galactoside-binding proteins in animals
      and fungi. We previously isolated cDNAs of 10 galectin and galectin-like genes
      (lec-1 to lec-6 and lec-8 to lec-11) from Caenorhabditis elegans and
      characterized the carbohydrate-binding properties of their recombinant proteins.
      In the present study, we isolated cDNA corresponding to an open reading frame of
      the DC2.3a gene from C. elegans total RNA; this cDNA encodes another potential
      galectin. A recombinant DC2.3a protein was expressed in Escherichia coli and used
      for analysis. The protein displayed hemagglutinating activity against rabbit
      erythrocytes, bound to an asialofetuin-Sepharose column, and was eluted with
      lactose. Furthermore, frontal affinity chromatography (FAC) analysis confirmed
      that DC2.3a recognized oligosaccharides with a non-reducing terminal galactose.
      According to these results, we designated DC2.3 as lec-12. The carbohydrate
      binding property of the recombinant DC2.3a/LEC-12a was essentially similar to
      that of LEC-6. Additionally, DC2.3a/LEC-12a and LEC-6 showed higher affinities
      for the galactosebeta1->4fucose (Galbeta1->4Fuc) disaccharide than for N
      acetyllactosamine. This suggests that the principal recognition unit is the
      Galbeta1->4Fuc disaccharide as in the case of the C. elegans galectins. However,
      the recombinant DC2.3a/LEC-12a showed weak affinity for N-glycan E3, which was
      previously shown to be a preferential endogenous ligand for LEC-6. The DC2.3a/LEC
      12a endogenous ligand structures appear to be somewhat different but contain the
      same galactose-fucose recognition motif.

PMID- 21963510
TI  - Comparison of the effects of pantethine and fursultiamine on plasma
      gastrointestinal peptide levels in healthy volunteers.
AB  - Pantethine and fursultiamine have been evaluated for their clinical usefulness in
      the treatment and prevention of uncomplicated postoperative adhesive intestinal
      obstruction. In recent years, the actions of drugs used to treat gastrointestinal
      diseases have been elucidated pharmacologically from the viewpoints of
      gastrointestinal peptide levels. We examined the effects of pantethine and
      fursultiamine on plasma levels of calcitonin gene-related peptide (CGRP)-,
      vasoactive intestinal polypeptide (VIP)-, motilin- and substance P (SP)-like
      immunoreactive substances (IS) in healthy subjects. An open-labeled study was
      conducted on five healthy volunteers. Each subject was administered a single oral
      dose of pantethine, fursultiamine and placebo at intervals of one month. Venous
      blood samples were collected before and at 20, 40, 60, 90, 120, 180 and 240 min
      after each administration. Plasma peptide levels were measured using a highly
      sensitive enzyme immunoassay. A single oral dose of pantethine resulted in
      significant increases of plasma CGRP- and VIP-IS levels compared to placebo.
      Furthermore, areas under the plasma concentration-time curves (AUC(0-240)) of
      CGRP- and VIP-IS were significantly higher after pantethine administration
      compared with placebo. On the other hand, fursultiamine had no effect on plasma
      levels and AUC(0-240) of CGRP-, VIP-, motilin- and SP-IS. This study demonstrated
      the different effects of pantethine and fursultiamine from the viewpoint of
      plasma gastrointestinal peptide changes. The pharmacological effects of
      pantethine may be closely related to the changes in plasma CGRP- and VIP-IS
      levels.

PMID- 21963511
TI  - Interleukin-1 controls the constitutive expression of the Cyp7a1 gene by
      regulating the expression of Cyp7a1 transcriptional regulators in the mouse
      liver.
AB  - Our previous study using interleukin-1alpha/beta-knockout (IL-1-KO) and wild-type
      (WT) mice demonstrated that IL-1 acts as a positive factor for constitutive gene
      expression of hepatic cytochrome P4507a1 (Cyp7a1). In this study, to clarify the
      role of IL-1 in the expression of the hepatic Cyp7a1 gene, we focused on Cyp7a1
      transcriptional regulators such as alpha-fetoprotein transcription factor (FTF),
      liver X receptor alpha (LXRalpha), hepatocyte nuclear factor 4alpha (HNF4alpha)
      and small heterodimer partner (SHP) and examined the effects of IL-1 on their
      gene expression by real-time reverse-transcription polymerase chain reaction
      using IL-1-KO and WT mice. We observed no significant differences between sex
      matched IL-1-KO and WT mice with regard to gene expression levels of FTF,
      LXRalpha, and HNF4alpha, all of which are positive transcriptional regulators for
      the Cyp7a1 gene. However, interindividual differences in hepatic FTF and LXRalpha
      expression were closely dependent on the gene expression level(s) of hepatic IL-1
      and tumor necrosis factor-alpha (TNF-alpha), while interindividual differences in
      hepatic HNF4alpha were clearly correlated with the expression of IL-1, but not
      TNF-alpha. In contrast, the gene expression level of SHP, which is a negative
      transcriptional regulator of the Cyp7a1 gene through inhibition of FTF function,
      was higher in IL-1-KO mice than in sex-matched WT mice. These findings
      demonstrate that, like TNF-alpha, IL-1 positively controls the gene expression of
      Cyp7a1 transcriptional upregulators but, in contrast to the previously reported
      action of TNF-alpha, IL-1 also acts to downregulate SHP gene expression.

PMID- 21963512
TI  - Identification and detection method for genetically modified papaya resistant to
      papaya ringspot virus YK strain.
AB  - Unauthorized genetically modified (GM) papaya (Carica papaya LINNAEUS) was
      detected in a commercially processed product, which included papaya as a major
      ingredient, in Japan. We identified the transgenic vector construct generated
      based on resistance to infection with the papaya ringspot virus (PRSV) YK strain.
      A specific detection method to qualitatively monitor papaya products for
      contamination with the GM papaya was developed using the real-time polymerase
      chain reaction.

PMID- 21963513
TI  - Increased plasma visfatin concentration is a marker of an atherogenic metabolic
      profile.
AB  - BACKGROUND AND AIMS: Visfatin is associated with atherosclerosis-related
      diseases. We assessed in non-diabetic individuals the association of plasma
      visfatin levels with cardiovascular disease (CVD) risk and the atherosclerosis
      related metabolic variables. METHODS AND RESULTS: When study population (n = 179,
      age 49 +/- 11 years) was divided according to visfatin tertiles, the 10-year CVD
      Framingham risk scores were significantly increased in the top visfatin tertile.
      We observed a positive association between visfatin tertiles with waist
      circumference and blood pressure, as well as with total cholesterol and
      triglyceride levels, but not with apolipoprotein C-III, fibrinogen or pre-beta1
      high density lipoprotein (HDL). The percentage of large HDL subclasses was
      significantly lower and the percentage of small HDL subclasses over the HDL-C
      concentration was significantly higher in the top visfatin tertile compared with
      the other tertiles. The atherogenic small dense low density lipoprotein
      subclasses (sdLDL-C) were significantly increased in the top visfatin tertile
      compared with the lower tertiles. High sensitivity C-reactive protein (hsCRP)
      concentration was significantly increased in the top visfatin tertile compared
      with the lower tertiles. Although age and sex distribution did not differ between
      visfatin tertiles, the simultaneous adjustment for these parameters attenuated
      the significance of the differences observed in sdLDL-C and hsCRP levels.
      Similarly, after adjustment for hsCRP or waist circumference, only triglycerides
      and blood pressure levels, as well as the distribution of HDL subclasses,
      remained significantly different between visfatin tertiles. CONCLUSIONS: Our
      results support a role for visfatin in the detection of subjects with many
      metabolic abnormalities, which result in increased CVD risk.

PMID- 21963514
TI  - Nonopioid placebo analgesia is mediated by CB1 cannabinoid receptors.
AB  - Placebo analgesia is mediated by both opioid and nonopioid mechanisms, but so far
      nothing is known about the nonopioid component. Here we show that the specific
      CB1 cannabinoid receptor antagonist 5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4
      methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (rimonabant or SR141716)
      blocks nonopioid placebo analgesic responses but has no effect on opioid placebo
      responses. These findings suggest that the endocannabinoid system has a pivotal
      role in placebo analgesia in some circumstances when the opioid system is not
      involved.

PMID- 21963516
TI  - Genomic risk of hepatitis C-related hepatocellular carcinoma.
AB  - To identify the genetic susceptibility factor(s) for hepatitis C virus-induced
      hepatocellular carcinoma (HCV-induced HCC), we conducted a genome-wide
      association study using 432,703 autosomal SNPs in 721 individuals with HCV
      induced HCC (cases) and 2890 HCV-negative controls of Japanese origin. Eight SNPs
      that showed possible association (P <1 10(-5)) in the genome-wide association
      study were further genotyped in 673 cases and 2596 controls. We found a
      previously unidentified locus in the 50 flanking region of MICA on 6p21.33
      (rs2596542, P(combined) = 4.21 10(-13), odds ratio = 1.39) to be strongly
      associated with HCV induced HCC. Subsequent analyses using individuals with
      chronic hepatitis C (CHC) indicated that this SNP is not associated with CHC
      susceptibility (P = 0.61) but is significantly associated with progression from
      CHC to HCC (P = 3.13 10(-8)). We also found that the risk allele of rs2596542 was
      associated with lower soluble MICA protein levels in individuals with HCV-induced
      HCC (P = 1.38 10(-13)).

PMID- 21963517
TI  - Phase II, open-label study of brivanib as first-line therapy in patients with
      advanced hepatocellular carcinoma.

PMID- 21963515
TI  - The calcineurin inhibitor tacrolimus activates the renal sodium chloride
      cotransporter to cause hypertension.
AB  - Calcineurin inhibitors (CNIs) are immunosuppressive drugs that are used widely to
      prevent rejection of transplanted organs and to treat autoimmune disease.
      Hypertension and renal tubule dysfunction, including hyperkalemia, hypercalciuria
      and acidosis, often complicate their use. These side effects resemble familial
      hyperkalemic hypertension, a genetic disease characterized by overactivity of the
      renal sodium chloride cotransporter (NCC) and caused by mutations in genes
      encoding WNK kinases. We hypothesized that CNIs induce hypertension by
      stimulating NCC. In wild-type mice, the CNI tacrolimus caused salt-sensitive
      hypertension and increased the abundance of phosphorylated NCC and the NCC
      regulatory kinases WNK3, WNK4 and SPAK. We demonstrated the functional importance
      of NCC in this response by showing that tacrolimus did not affect blood pressure
      in NCC-knockout mice, whereas the hypertensive response to tacrolimus was
      exaggerated in mice overexpressing NCC. Moreover, hydrochlorothiazide, an NCC
      blocking drug, reversed tacrolimus-induced hypertension. These observations were
      extended to humans by showing that kidney transplant recipients treated with
      tacrolimus had a greater fractional chloride excretion in response to
      bendroflumethiazide, another NCC-blocking drug, than individuals not treated with
      tacrolimus; renal NCC abundance was also greater. Together, these findings
      indicate that tacrolimus-induced chronic hypertension is mediated largely by NCC
      activation, and suggest that inexpensive and well-tolerated thiazide diuretics
      may be especially effective in preventing the complications of CNI treatment.

PMID- 21963518
TI  - Immunosuppression and HCV recurrence after liver transplantation.
AB  - HCV related liver disease is the most common indication for liver
      transplantation. Recurrence of HCV infection is universal and has a substantial
      impact on patient and graft survival. Immunosuppression is a major factor
      responsible for the accelerated recurrence and compressed natural history of
      recurrent HCV infection. Accumulating experience has provided data to support
      certain strategies for immunosuppressive regimens. From the available evidence,
      more severe recurrence results from repeated bolus corticosteroid therapy and
      anti-lymphocyte antibodies used to treat rejection. Low dose and slow tapering of
      steroids are better than high dose maintenance and/or rapid tapering. Recent meta
      analyses favour steroid-free regimens but these are complicated to interpret as
      the absence of steroids may simply represent less immunopotency. There is no
      difference in HCV recurrence between tacrolimus and cyclosporine regimens, but
      tacrolimus increases graft and patient survival in HCV transplanted patients.
      There may be a beneficial effect of maintenance azathioprine given for 6 months
      or longer. There is no conclusive evidence for benefit of mycophenolate and
      interleukin-2 receptor blockers. Few data are available for mTOR inhibitors.
      Better evidence is needed to establish the optimal immunosuppressive regimen for
      HCV recipients and more randomized trials should be performed.

PMID- 21963519
TI  - The adolescent and liver transplantation.
AB  - The outcome of liver transplantation is usually reported in terms of graft and
      patient survival, medical and surgical complications, and quality of life, but
      when it comes to transplanted adolescents such conventional parameters are unable
      to give a full account of their life with a new liver, and their transition from
      adolescence to adulthood is a time when they are particularly vulnerable.
      Adolescents with liver transplants have excellent survival rates, over 80% of
      them surviving more than 10 years. Graft loss is most often associated with
      complications such as chronic rejection, hepatic artery thrombosis, and biliary
      complications. Calcineurin inhibitors may have various side effects, including
      hypertension and nephrotoxicity. Liver-transplanted adolescents are also exposed
      to viral infections, among which Epstein-Barr virus is very common and associated
      with the onset of post-transplant lymphoproliferative disorders. Growth
      retardation may also be an issue in some liver transplant recipients. Future
      studies will determine the best way to assess the functional immune status of
      adolescents with a transplanted liver with a view to ensuring the best treatment
      to induce tolerance without the complications of excessive immunosuppression.
      Schooling may be disrupted due to adolescent transplant recipients' poor
      adherence. Non-adherence is associated with a poor medical outcome. Both physical
      and psychosocial functioning is reportedly lower among young liver transplant
      recipients than in the general population.

PMID- 21963520
TI  - Yes! Statins can be given to liver patients.

PMID- 21963521
TI  - HIF-1alpha is a major and complex player in alcohol induced liver diseases.

PMID- 21963522
TI  - Empowering industrial research with shared biomedical vocabularies.
AB  - The life science industries (including pharmaceuticals, agrochemicals and
      consumer goods) are exploring new business models for research and development
      that focus on external partnerships. In parallel, there is a desire to make
      better use of data obtained from sources such as human clinical samples to inform
      and support early research programmes. Success in both areas depends upon the
      successful integration of heterogeneous data from multiple providers and
      scientific domains, something that is already a major challenge within the
      industry. This issue is exacerbated by the absence of agreed standards that
      unambiguously identify the entities, processes and observations within
      experimental results. In this article we highlight the risks to future
      productivity that are associated with incomplete biological and chemical
      vocabularies and suggest a new model to address this long-standing issue.

PMID- 21963523
TI  - Neurodevelopmental performance among school age children in rural Guatemala is
      associated with prenatal and postnatal exposure to carbon monoxide, a marker for
      exposure to woodsmoke.
AB  - We investigated whether early life chronic exposure to woodsmoke, using personal
      passive 48-h carbon monoxide (CO) as an indicator, is associated with children's
      neurodevelopmental and behavioral performance. CO measures were collected every 3
      months from 2002 to 2005 among mother-child dyads during the Randomized Exposure
      Study of Pollution Indoors and Respiratory Effects (RESPIRE) stove intervention
      trial in San Marcos, Guatemala. From March to June, 2010, study children of age 6
      7 years, performed a follow-up non-verbal, culturally adapted neurodevelopmental
      assessment. We found inverse associations between CO exposure of pregnant mothers
      during their 3rd trimesters (m=3.8ppm +/- 3.0ppm; range: 0.6-12.5 ppm) and child
      neuropsychological performance. Scores on 4 out of 11 neuropsychological tests
      were significantly associated with mothers' 3rd trimester CO exposures, including
      visuo-spatial integration (p<0.05), short-term memory recall (p<0.05), long-term
      memory recall (p<0.05), and fine motor performance (p<0.01) measured using the
      Bender Gestalt-II's Copy, Immediate Recall, and an adapted version of a Delayed
      Recall Figures drawing, and the Reitan-Indiana's Finger Tapping Tests,
      respectively. These 4 significant finding persisted with adjustment for child
      sex, age, visual acuity, and household assets (socio-economic status). Summary
      performance scores were also significantly associated with maternal 3rd trimester
      CO when adjusted for these covariates. Other variables accounting for variance
      but were excluded in our final multiple regression models included the following:
      HOME environment stimulation score, child examiner, WHO height-for-age
      percentile, and age that the infant stopped breastfeeding. This seems to be the
      first study on woodsmoke exposure and neurodevelopment, and the first
      longitudinal birth cohort study on chronic early life CO exposures, determined by
      high quality measures of mothers' and infants' personal CO exposures, and using
      well-established, reliable child neuropsychological tests. Further research is
      needed to replicate our results and inform future interventions and air quality
      standards for woodsmoke and CO.

PMID- 21963524
TI  - Manganese potentiates LPS-induced heme-oxygenase 1 in microglia but not
      dopaminergic cells: role in controlling microglial hydrogen peroxide and
      inflammatory cytokine output.
AB  - Excessive manganese (Mn) exposure increases output of glial-derived inflammatory
      products, which may indirectly contribute to the neurotoxic effects of this
      essential metal. In microglia, Mn increases hydrogen peroxide (H(2)O(2)) release
      and potentiates lipopolysaccharide (LPS)-induced cytokines (TNF-alpha, IL-6) and
      nitric oxide (NO). Inducible heme-oxygenase (HO-1) plays a role in the regulation
      of inflammation and its expression is upregulated in response to oxidative
      stressors, including metals and LPS. Because Mn can oxidatively affect neurons
      both directly and indirectly, we investigated the effect of Mn exposure on the
      induction of HO-1 in resting and LPS-activated microglia (N9) and dopaminergic
      neurons (N27). In microglia, 24h exposure to Mn (up to 250 MUM) had minimal
      effects on its own, but it markedly potentiated LPS (100 ng/ml)-induced HO-1
      protein and mRNA. Inhibition of microglial HO-1 activity with two different
      inhibitors indicated that HO-1 is a positive regulator of the Mn-potentiated
      cytokine output and a negative regulator of the Mn-induced H(2)O(2) output. Mn
      enhancement of LPS-induced HO-1 does not appear to be dependent on H(2)O(2) or
      NO, as Mn+LPS-induced H(2)O(2) release was not greater than the increase induced
      by Mn alone and inhibition of iNOS did not change Mn potentiation of HO-1.
      However, because Mn exposure potentiated the LPS-induced nuclear expression of
      small Maf proteins, this may be one mechanism Mn uses to affect the expression of
      HO-1 in activated microglia. Finally, the potentiating effects of Mn on HO-1
      appear to be glia-specific for Mn, LPS, or Mn+LPS did not induce HO-1 in N27
      neuronal cells.

PMID- 21963525
TI  - Spontaneous transformation of adult mesenchymal stem cells from cynomolgus
      macaques in vitro.
AB  - Mesenchymal stem cells (MSCs) have shown potential clinical utility in cell
      therapy and tissue engineering, due to their ability to proliferate as well as to
      differentiate into multiple lineages, including osteogenic, adipogenic, and
      chondrogenic specifications. Therefore, it is crucial to assess the safety of
      MSCs while extensive expansion ex vivo is a prerequisite to obtain the cell
      numbers for cell transplantation. Here we show that MSCs derived from adult
      cynomolgus monkey can undergo spontaneous transformation following in vitro
      culture. In comparison with MSCs, the spontaneously transformed mesenchymal cells
      (TMCs) display significantly different growth pattern and morphology, reminiscent
      of the characteristics of tumor cells. Importantly, TMCs are highly tumorigenic,
      causing subcutaneous tumors when injected into NOD/SCID mice. Moreover, no
      multiple differentiation potential of TMCs is observed in vitro or in vivo,
      suggesting that spontaneously transformed adult stem cells may not necessarily
      turn into cancer stem cells. These data indicate a direct transformation of
      cynomolgus monkey MSCs into tumor cells following long-term expansion in vitro.
      The spontaneous transformation of the cultured cynomolgus monkey MSCs may have
      important implications for ongoing clinical trials and for models of oncogenesis,
      thus warranting a more strict assessment of MSCs prior to cell therapy.

PMID- 21963526
TI  - Chronic fluoxetine treatment alters cardiovascular functions in unanesthetized
      rats.
AB  - In the present study, we investigated the effects induced by fluoxetine treatment
      (10 mg/kg) for either 1 or 21 consecutive days on arterial pressure and heart
      rate basal levels, baroreflex activity, hemodynamic responses to vasoactive
      agents and cardiovascular responses to acute restraint stress. Mild hypertension
      was observed after 21 days of treatment, but not after administration for 1 day.
      Moreover, chronic treatment affected the baroreflex control of heart rate, which
      was characterized by a reduced reflex tachycardia and an enhanced bradycardiac
      baroreflex response. The pressor responses to systemic administration of the
      selective alpha(1)-adrenoceptor agonist phenylephrine, as well as the depressor
      responses to systemic infusion of the nitric oxide donor sodium nitroprusside,
      were reduced after chronic fluoxetine treatment. Fluoxetine treatment for 21 days
      reduced both the pressor and tachycardiac responses evoked by acute restraint
      stress. In conclusion, the results indicate the development of mild hypertension
      after chronic fluoxetine treatment. This effect was followed by changes in the
      baroreflex control of heart rate and altered vascular responsiveness to pressor
      and depressor agents, which may explain, at least in part, the increase in
      arterial pressure. Chronic fluoxetine treatment also affected cardiovascular
      responses to restraint stress, thus indicating that fluoxetine may affect
      cardiovascular adaptation under conditions of stress.

PMID- 21963527
TI  - Alpha amplitude and phase locking in obsessive-compulsive disorder during working
      memory.
AB  - Alpha event-related desynchronization (ERD) and synchronization are known to
      reflect brain activation and inhibition, respectively. Alpha phase locking seems
      to reflect the timing in the cortical process. In a previous study, lower alpha
      ERD was related to working memory in obsessive-compulsive disorder (OCD) patients
      than in controls during the retention and retrival phases, but not in the
      encoding phase. However, memory deficits in OCD patients are known to be related
      to executive failure during the encoding phase. Thus, focusing on the encoding
      phase, we tested the level of alpha amplitude and phase locking in OCD patients
      according to memory load. The EEGs of fifteen OCD patients and fifteen controls
      were recorded during a Sternberg working memory task. The behavioral performance
      of the OCD patients was normal. However, the OCD group yielded significantly
      lower ERD and stronger phase locking. As memory load rose, ERD and phase locking
      significantly increased in both groups. A difference in event-related alpha
      oscillation was observed in the encoding phase. Lower alpha modulation in the OCD
      patient simplied abnormality of the excitatory/inhibitory process in the brain,
      and increased phase locking might reflect excessive attentional excitability.

PMID- 21963528
TI  - Delayed psychophysiological recovery after self-concept-inconsistent negative
      performance feedback.
AB  - The identification of individual differences variables and environmental
      conditions that may be associated with poor psychophysiological recovery from
      stress or may serve as protective factors may be relevant in the context of
      physical and psychological health maintenance. In the present study, heart rate
      recovery from a mental arithmetic task was examined after participants received
      bogus performance-related feedback that could be consistent or inconsistent with
      their specific self-concept about their mental arithmetic skills. That way, the
      participants' beliefs about their own performance in the task were experimentally
      manipulated. Recovery of heart rate was examined in two time windows: (1) shortly
      after the participants had completed the task and had received positive or
      negative performance feedback and (2) 10 min after the task. In order to evaluate
      the dynamic of changes in more detail, speed of recovery (linear slope of the
      continuous beat-to-beat data) was analysed in addition to the degree of recovery
      (average heart rate decline during the five-minute observation periods). The
      results indicate that negative performance-related feedback may prolong
      psychophysiological responses to stressful conditions, in particular when the
      feedback is inconsistent with the domain-specific self-concept. In conjunction
      with other evidence these results support the assumption that positive emotional
      states in the context of stressful events may contribute to poor post-stress
      recovery. Overall, the findings are supportive of the "perseverative cognition
      hypothesis" according to which psychophysiological recovery may be delayed
      through continued cognitive representation of a negative experience.

PMID- 21963529
TI  - Ticks per thought or thoughts per tick? A selective review of time perception
      with hints on future research.
AB  - The last decade underwent a revival of interest in the perception of time and
      duration. The present short essay does not compete with the many other recent
      reviews and books on this topic. Instead, it is meant to emphasize the notion
      that humans (and most likely other animals) have at their disposal more than one
      time measuring device and to propose that they use these devices jointly to
      appraise the passage of time. One possible consequence of this conjecture is that
      the same physical duration can be judged differently depending on the reference
      'clock' used in any such judgment. As this view has not yet been tested
      empirically, several experimental manipulations susceptible to directly test it
      are suggested. Before, are summarized a number of its latent precursors, namely
      the relativity of perceived duration, current trends in modeling time perception
      and its neural and pharmacological substrate, the experimental literature
      supporting the existence of multiple 'clocks' and a selected number of
      experimental manipulations known to induce time perception illusions which
      together with many others are putatively accountable in terms of alternative
      clock readings.

PMID- 21963530
TI  - Does experimental research support psychoanalysis?
AB  - The question of whether a psychodynamic view is compatible with experimental
      research is still a challenging issue-especially for child and adolescent
      psychopathology-despite the influence of psychoanalytic theory in this field
      until the 1980s. In this article, is explored the relationship between
      psychodynamic theory and experimental research using examples of evidence-based
      studies in the fields of (i) psychotherapeutic intervention assessment, (ii)
      placebo response in children and adolescents, (iii) unconscious lasting traumatic
      effects in children and adolescents, (iv) psychodynamic-oriented psychological
      testing. There are now a sufficient number of evidence-based studies to support
      the use of psychodynamic therapy in mental disorders, particularly in personality
      disorder and anxious/depressive disorder. In addition, placebo responses in
      children and adolescents with internalizing disorders are significantly higher in
      major depression compared to obsessive-compulsive disorder or other anxiety
      disorders, which highlights differential psychopathologies regarding the
      experience of loss. Also, using an experimental task, psychoanalysts are able to
      identify, without explicit knowledge and above the level of chance, healthy
      adults whose siblings had experienced cancer during childhood. This experiment
      suggests that implicit information regarding a participant's history is conveyed
      in interpersonal exchanges that can be intuitively perceived by judges
      experienced in listening to free associations from a psychodynamic perspective.
      Finally, psychodynamic-oriented psychological testing may predict the transition
      to schizophrenia in adolescents with a history of manic/mixed episodes. It can be
      concluded that there are no discrepancies between psychodynamic views and
      experimental data, whether one tests psychotherapeutic approaches, discusses data
      from other fields such as psychopharmacology, or designs experiments based on
      psychodynamic theory.

PMID- 21963531
TI  - Towards a dialogue between psychoanalysis and neuroscience: connections that are
      both possible and necessary.
AB  - The author, a child psychiatrist, calls for a dialogue between psychoanalysis and
      neuroscience (both from his clinical joint practices with neuropediatricians and
      on a theoretical level) to found a new approach to the questions of
      neurodevelopmental and psychopathological disorders. He briefly discusses two
      examples. The first example is developmental and concerns the links between the
      archaic grasping reflex and adhesive identification. He shows how the phenomena
      observed in the two fields can find a logical sequence. The second example
      concerns a therapeutic technique (wrapping) that is used to soothe self-injurious
      behaviours in children with autism. Here, again, both approaches are used to
      better understand the phenomenon in question. Bridges must be built to open new
      theoretico-clinical and therapeutic collaborations. One could imagine data
      integration from these two heterogeneous subdomains to form a new complex
      subdomain, from which productivity is guaranteed.

PMID- 21963532
TI  - Computer-aided detection of small pulmonary nodules in chest radiographs: an
      observer study.
AB  - RATIONALE AND OBJECTIVES: To evaluate the impact of computer-aided detection
      (CAD, IQQA-Chest; EDDA Technology, Princeton Junction, NJ) used as second reader
      on the detection of small pulmonary nodules in chest radiography (CXR). MATERIALS
      AND METHODS: A total of 113 patients (mean age 62 years) with CT and CXR within 6
      weeks were selected. Fifty-nine patients showed 101 pulmonary nodules (diameter 5
      15mm); the remaining 54 patients served as negative controls. Six readers of
      varying experience individually evaluated the CXR without and with CAD as second
      reader in two separate reading sessions. The sensitivity per lesion, figure of
      merit (FOM), and mean false positive per image (mFP) were calculated.
      Institutional review board approval was waived. RESULTS: With CAD, the
      sensitivity increased for inexperienced readers (39% vs. 45%, P < .05) and
      remained unchanged for experienced readers (50% vs. 51%). The mFP
      nonsignificantly increased for both inexperienced and experienced readers (0.27
      vs. 0.34 and 0.16 vs. 0.21). The mean FOM did not significantly differ for
      readings without and with CAD irrespective of reader experience (0.71 vs. 0.71
      and 0.84 vs. 0.87). All readers together dismissed 33% of true-positive CAD
      candidates. False-positive candidates by CAD provoked 40% of all false-positive
      marks made by the readers. CONCLUSION: CAD improves the sensitivity of
      inexperienced readers for the detection of small nodules at the expense of loss
      of specificity. Overall performance by means of FOM was therefore not affected.
      To use CAD more beneficial, readers need to improve their ability to
      differentiate true from false-positive CAD candidates.

PMID- 21963533
TI  - [Association of insulin resistance to different anthropometric measures and
      cardiovascular risk factors in a non-diabetic population].
AB  - BACKGROUND AND OBJECTIVE: Insulin resistance (IR) has been directly related to
      obesity, particularly central obesity, and to other cardiovascular risk factors
      (CVRFs). Direct IR quantification is difficult in clinical practice, and indirect
      methods such as HOMA (homeostasis model assessment) have therefore been
      developed. The aim of this study was to assess the association of IR, as measured
      by HOMA, with different anthropometric measures and some CVRFs. MATERIALS AND
      METHODS: A cross-sectional, observational study was carried out in a general
      population sample older than 18 years in the province of Albacete, Spain. Sample
      size was 678 subjects. Participants completed a survey and underwent physical
      examinations and laboratory tests. Obesity measures included body mass index,
      waist perimeter, and sagittal abdominal diameter. Data analysis was performed
      using SPSS 15.0 software. RESULTS: Mean values of obesity measures were higher in
      males as compared to females and increased with age. IR prevalence was 39.8%. All
      assessed anthropometric measures, decreased HDL (high density lipoprotein)
      cholesterol and increased non-HDL cholesterol were independently associated to
      the risk of IR. CONCLUSIONS: A clear association exists between different
      anthropometrical measures and IR in the general population. There is also an
      association between lipid profile cahnges and the risk of experiencing IR.

PMID- 21963534
TI  - Age-related changes of body composition and abdominal adipose tissue assessed by
      bio-electrical impedance analysis and computed tomography.
AB  - Only scarce information is available on body composition changes with age
      measured simultaneously by electrical impedance and computed tomography. AIM: We
      aimed to describe the age-related changes of the body composition and adipose
      tissue distribution in Bulgarians. MATERIAL AND METHODS: This cross-sectional
      study included 130 participants (mean age 53+/-9.8 years, range 35-65), divided
      according to their body mass index (BMI): BMI <25.0 kg/m(2) (18 women, 12 men);
      BMI 25.0-34.9 kg/m(2) (50 women, 50 men). Body composition was assessed by
      bioelectrical impedance on a Tanita TBF-215 analyzer (Tanita Corp., Tokyo,
      Japan). The abdominal fat was measured by computed tomography on a CT/L scanner
      (GE Medical Systems, USA). RESULTS: Increasing age was associated with a mean
      decrease in body weight by 268 g per year in the normal weight subjects and by
      390 g in the overweight ones as well as with a fat-free mass decrease of 321 g
      and of 291 g per year respectively (p<0.001). One year of increasing age was
      associated with a mean increase of visceral adipose tissue by 2.43 cm(2) in the
      overweight group and by 2.68 cm(2) in the normal weight subjects and with a
      decrease of the subcutaneous adipose tissue by 2.30 cm(2) per year in the latter
      group (p<0.001). The association of fat mass and fat-free mass with age in men
      and women was best described by quadratic equations (both increased until the age
      of 45-50 and decreased thereafter). CONCLUSIONS: Our data showed a significant
      association between age and decreasing fat-free mass, increasing fat mass and
      abdominal fat accumulation.

PMID- 21963536
TI  - Selective repression of Notch pathway target gene transcription.
AB  - The Notch signaling pathway regulates metazoan development, in part, by directly
      controlling the transcription of target genes. For a given cellular context,
      however, only subsets of the known target genes are transcribed when the pathway
      is activated. Thus, there are context-dependent mechanisms that selectively
      maintain repression of target gene transcription when the Notch pathway is
      activated. This review focuses on molecular mechanisms that have been recently
      reported to mediate selective repression of Notch pathway target gene
      transcription. These mechanisms are essential for generating the complex spatial
      and temporal expression patterns of Notch target genes during development.

PMID- 21963535
TI  - The influence of pre-sleep cognitive arousal on sleep onset processes.
AB  - Cognitive hyperarousal, resulting in enhanced cognitive activation, has been
      cited as an important contributor to the development and preservation of
      insomnia. To further understand this process, our study examined the effects of
      acutely-induced pre-sleep cognitive hyperarousal on sleep onset processes in
      healthy volunteers. Following an adaptation night, 15 subjects slept two nights
      in our sleep laboratory: one reference night and another one with cognitive
      arousal induction, in a counterbalanced order. In the cognitive arousal
      condition, subjects worked through half an hour of cognitive tasks without
      interference of an emotional component prior to retiring to bed. Objective sleep
      onset latency was significantly prolonged in the cognitive arousal condition
      compared to the reference condition. Significantly more high frequency activity
      was recorded during the first and second deep-sleep period. Moreover, differences
      in heart rate and proximal temperature during and after sleep onset were observed
      in the nights after the cognitive induction. Pre-sleep cognitive activation
      successfully induced a significant cognitive load and activation in our subjects
      to influence subsequent sleep (onset) processes.

PMID- 21963537
TI  - Trachealess (Trh) regulates all tracheal genes during Drosophila embryogenesis.
AB  - The Drosophila trachea is a branched tubular epithelia that transports oxygen and
      other gases. trachealess (trh), which encodes a bHLH-PAS transcription factor, is
      among the first genes to be expressed in the cells that will form the trachea. In
      the absence of trh, tracheal cells fail to invaginate to form tubes and remain on
      the embryo surface. Expression of many tracheal-specific genes depends on trh,
      but all of the known targets have relatively minor phenotypes compared to loss of
      trh, suggesting that there are additional targets. To identify uncharacterized
      transcriptional targets of Trh and to further understand the role of Trh in
      embryonic tracheal formation, we performed an in situ hybridization screen using
      a library of ~100 tracheal-expressed genes identified by the Berkeley Drosophila
      Genome Project (BDGP). Surprisingly, expression of every tracheal gene we tested
      was dependent on Trh, suggesting a major role for Trh in activation and
      maintenance of tracheal gene expression. A re-examination of the interdependence
      of the known early-expressed transcription factors, including trh, ventral
      veinless (vvl) and knirps/knirps-related (kni/knrl), suggests a new model for how
      gene expression is controlled in the trachea, with trh regulating expression of
      vvl and kni, but not vice versa. A pilot screen for the targets of Vvl and
      Kni/Knrl revealed that Vvl and Kni have only minor roles compared to Trh.
      Finally, genome-wide microarray experiments identified additional Trh targets and
      revealed that a variety of biological processes are affected by the loss of trh.

PMID- 21963538
TI  - A dual function of Drosophila capping protein on DE-cadherin maintains epithelial
      integrity and prevents JNK-mediated apoptosis.
AB  - E-cadherin plays a pivotal role in epithelial cell polarity, cell signalling and
      tumour suppression. However, how E-cadherin dysfunction promotes tumour
      progression is poorly understood. Here we show that the actin-capping protein
      heterodimer, which regulates actin filament polymerization, has a dual function
      on DE-cadherin in restricted Drosophila epithelia. Knocking down capping protein
      in the distal wing disc epithelium disrupts DE-cadherin and Armadillo
      localization at adherens junctions and upregulates DE-cadherin transcription. In
      turn, DE-cadherin provides an active signal, which prevents Wingless signalling
      and promotes JNK-mediated apoptosis. However, when cells are kept alive with the
      Caspase inhibitor P35, the activity of the JNK pathway and of the Yorkie oncogene
      trigger massive proliferation of cells that fail to stably retain associations
      with their neighbours. Moreover, loss of capping protein cooperates with the Ras
      oncogene to induce massive tissue overgrowth. Taken together, our findings argue
      that in some epithelia, the dual effect of capping protein loss on DE-cadherin
      triggers the elimination of mutant cells, preventing them from proliferating.
      However, the appearance of a second mutation that blocks cell death may allow for
      the development of some epithelial tumours.

PMID- 21963540
TI  - Charity care in New Jersey: the cost and the consequences.

PMID- 21963539
TI  - Functional dissection of phosphorylation of Disheveled in Drosophila.
AB  - Disheveled/Dsh proteins (Dvl in mammals) are core components of both Wnt/Wg
      signaling pathways: canonical beta-catenin signaling and Frizzled (Fz)-planar
      cell polarity (PCP) signaling. Although Dsh is a key cytoplasmic component of
      both Wnt/Fz-pathways, regulation of its signaling specificity is not well
      understood. Dsh is phosphorylated, but the functional significance of its
      phosphorylation remains unclear. We have systematically investigated the
      phosphorylation of Dsh by combining mass-spectrometry analyses, biochemical
      studies, and in vivo genetic methods in Drosophila. Our approaches identified
      multiple phospho-residues of Dsh in vivo. Our data define three novel and
      unexpected conclusions: (1) strikingly and in contrast to common assumptions, all
      conserved serines/threonines are non-essential for Dsh function in either
      pathway; (2) phosphorylation of conserved Tyrosine473 in the DEP domain is
      critical for PCP-signaling - Dsh(Y473F) behaves like a PCP-specific allele; and
      (3) defects associated with the PCP specific dsh(1) allele, Dsh(K417M), located
      within a putative Protein Kinase C consensus site, are likely due to a post
      translational modification requirement of Lys417, rather than phosphorylation
      nearby. In summary, our combined data indicate that while many Ser/Thr and Tyr
      residues are indeed phosphorylated in vivo, strikingly most of these
      phosphorylation events are not critical for Dsh function with the exception of
      DshY473.

PMID- 21963541
TI  - Screening for depression in general medical practice: how can natural sadness be
      distinguished from major depressive disorder?

PMID- 21963542
TI  - Cultural competency: across cultures between physicians and patients.

PMID- 21963543
TI  - New law affecting the New Jersey medical community: cultural competency training.

PMID- 21963544
TI  - The defendant physician's deposition: some traps and some tips.

PMID- 21963545
TI  - Effective communication: awareness is key.

PMID- 21963546
TI  - Energy efficiency: conservation and renewable technology can help your practice
      manage rising costs.

PMID- 21963547
TI  - Budget cuts shouldn't bleed New Jersey's healthcare system.

PMID- 21963548
TI  - Medical liability tort reform: a battle of intrigue continues.

PMID- 21963549
TI  - New law affecting the New Jersey medical community: changes to the New Jersey
      Prescription Blanks (NJPBs) format.

PMID- 21963550
TI  - Membrane labeling and immobilization via copper-free click chemistry.
AB  - Copper-free click chemistry was employed to derivatize membrane bilayers. This
      approach uses an azido-lipid conjugate presented on liposomes, which can be
      labeled in bioorthogonal fashion via cyclooctyne-tagged reagents. An
      immobilization-based approach using streptavidin-coated microplates was exploited
      to evaluate membrane derivatization.

PMID- 21963551
TI  - Sympathetic influence on cerebral blood flow and metabolism during exercise in
      humans.
AB  - This review focuses on the possibility that autonomic activity influences
      cerebral blood flow (CBF) and metabolism during exercise in humans. Apart from
      cerebral autoregulation, the arterial carbon dioxide tension, and neuronal
      activation, it may be that the autonomic nervous system influences CBF as
      evidenced by pharmacological manipulation of adrenergic and cholinergic
      receptors. Cholinergic blockade by glycopyrrolate blocks the exercise-induced
      increase in the transcranial Doppler determined mean flow velocity (MCA Vmean).
      Conversely, alpha-adrenergic activation increases that expression of cerebral
      perfusion and reduces the near-infrared determined cerebral oxygenation at rest,
      but not during exercise associated with an increased cerebral metabolic rate for
      oxygen (CMRO(2)), suggesting competition between CMRO(2) and sympathetic control
      of CBF. CMRO(2) does not change during even intense handgrip, but increases
      during cycling exercise. The increase in CMRO(2) is unaffected by beta-adrenergic
      blockade even though CBF is reduced suggesting that cerebral oxygenation becomes
      critical and a limited cerebral mitochondrial oxygen tension may induce fatigue.
      Also, sympathetic activity may drive cerebral non-oxidative carbohydrate uptake
      during exercise. Adrenaline appears to accelerate cerebral glycolysis through a
      beta2-adrenergic receptor mechanism since noradrenaline is without such an
      effect. In addition, the exercise-induced cerebral non-oxidative carbohydrate
      uptake is blocked by combined beta 1/2-adrenergic blockade, but not by beta1
      adrenergic blockade. Furthermore, endurance training appears to lower the
      cerebral non-oxidative carbohydrate uptake and preserve cerebral oxygenation
      during submaximal exercise. This is possibly related to an attenuated
      catecholamine response. Finally, exercise promotes brain health as evidenced by
      increased release of brain-derived neurotrophic factor (BDNF) from the brain.

PMID- 21963552
TI  - The neurobiology of insect olfaction: sensory processing in a comparative
      context.
AB  - The simplicity and accessibility of the olfactory systems of insects underlie a
      body of research essential to understanding not only olfactory function but also
      general principles of sensory processing. As insect olfactory neurobiology takes
      advantage of a variety of species separated by millions of years of evolution,
      the field naturally has yielded some conflicting results. Far from impeding
      progress, the varieties of insect olfactory systems reflect the various natural
      histories, adaptations to specific environments, and the roles olfaction plays in
      the life of the species studied. We review current findings in insect olfactory
      neurobiology, with special attention to differences among species. We begin by
      describing the olfactory environments and olfactory-based behaviors of insects,
      as these form the context in which neurobiological findings are interpreted.
      Next, we review recent work describing changes in olfactory systems as
      adaptations to new environments or behaviors promoting speciation. We proceed to
      discuss variations on the basic anatomy of the antennal (olfactory) lobe of the
      brain and higher-order olfactory centers. Finally, we describe features of
      olfactory information processing including gain control, transformation between
      input and output by operations such as broadening and sharpening of tuning
      curves, the role of spiking synchrony in the antennal lobe, and the encoding of
      temporal features of encounters with an odor plume. In each section, we draw
      connections between particular features of the olfactory neurobiology of a
      species and the animal's life history. We propose that this perspective is
      beneficial for insect olfactory neurobiology in particular and sensory
      neurobiology in general.

PMID- 21963554
TI  - Anti-inflammatory activity of an ethanolic Caesalpinia sappan extract in human
      chondrocytes and macrophages.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Caesalpinia sappan is a common remedy in
      Traditional Chinese Medicine and possesses diverse biological activities
      including anti-inflammatory properties. Osteoarthritis (OA) is a degenerative
      joint disease with an inflammatory component that drives the degradation of
      cartilage extracellular matrix. In order to provide a scientific basis for the
      applicability of Caesalpinia sappan in arthritic diseases, the present study
      aimed to assess the effects of an ethanolic Caesalpinia sappan extract (CSE) on
      human chondrocytes and macrophages. MATERIALS AND METHODS: Primary human
      chondrocytes were isolated from cartilage specimens of OA patients. Primary
      cells, SW1353 chondrocytes and THP-1 macrophages were serum-starved and
      pretreated with different concentrations of CSE prior to stimulation with 10
      ng/ml of interleukin-1beta (IL-1beta) or lipopolysaccharide (LPS). Following
      viability tests, nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha)
      were evaluated by Griess assay and ELISA, respectively. Using validated real-time
      PCR assays, mRNA levels of IL-1beta, TNF-alpha, inducible nitric oxide synthase
      (iNOS), and cyclooxygenase-2 (COX-2) were quantified. SW1353 cells were
      cotransfected with a COX-2 luciferase reporter plasmid and nuclear factor-kappa-B
      (NF-kappaB) p50 and p65 expression vectors in the presence or absence of CSE.
      RESULTS: CSE dose-dependently inhibited the expression of pro-inflammatory
      cytokines IL-1beta and TNF-alpha in IL-1beta-stimulated chondrocytes and LPS
      stimulated THP-1 macrophages. CSE further suppressed the synthesis of NO in
      primary OA chondrocytes by blocking iNOS mRNA expression. The inhibition of COX-2
      transcription was found to be related with the CSE inhibition of the p65/p50
      driven transactivation of the COX-2 promoter. CONCLUSIONS: The present report is
      first to demonstrate the anti-inflammatory activity of CSE in an in vitro cell
      model of joint inflammation. CSE can effectively abrogate the IL-1beta-induced
      over-expression of inflammatory mediators at the transcriptional level in human
      chondrocytes and macrophages, most likely by inhibiting NF-kappaB (p65/p50)
      signaling. Blockade of IL-1beta-induced NF-kappaB signaling and its downstream
      pro-inflammatory targets by CSE may be beneficial for reducing cartilage
      breakdown in arthritis.

PMID- 21963555
TI  - Hepatoprotective effect and its possible mechanism of Coptidis rhizoma aqueous
      extract on carbon tetrachloride-induced chronic liver hepatotoxicity in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Coptidis rhizoma is traditionally used for heat
      clearing and toxic-scavenging and it belongs to liver meridian in Chinese
      medicine practice. Clinically, Coptidis rhizoma can be used for hepatic and
      biliary disorders, yet details in the therapies of liver diseases and underlying
      mechanism(s) remain unclear. Our previous study demonstrated that Coptidis
      rhizoma aqueous extract (CRAE) against CCl(4)-induced acute liver damage was
      related to antioxidant property. In the present study, the protection of CRAE on
      chronic liver damage induced by carbon tetrachloride (CCl(4)) in rats and its
      related mechanism were explored. MATERIALS AND METHODS: The CCl(4)-induced
      chronic liver damage model was established, and CRAE's protective effect was
      examined. Serum aspartate aminotransferase (AST) and alanine aminotransferase
      (ALT) activity, serum and liver superoxide dismutase (SOD) activity were then
      measured. The histological changes were observed under microscopy and then
      computed in numerical score. The normal or damaged cells were isolated and
      related signaling pathway was evaluated. RESULT: Serum AST and ALT activities
      were significantly decreased in rats treated with different doses of CRAE,
      indicating its protective effect against CCl(4)-induced chronic liver damage.
      Observation on serum SOD activity revealed that CRAE might act as an anti-oxidant
      agent against CCl(4)-induced chronic oxide stress. Histological study supported
      these observations. Erk1/2 inhibition may take part into CRAE's effect on
      preventing hepatocyte from apoptosis when exposed to oxidative stress.
      CONCLUSION: CRAE showed protective effect against CCl(4)-induced chronic liver
      damage in rats and its potential as an agent in the treatment of chronic liver
      diseases by protecting hepatocyte from injury.

PMID- 21963556
TI  - Prediagnostic methods for the hemolysis of herbal medicine injection.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The Xue-Sai-Tong injection, a traditional Chinese
      medicine injection with total saponins extracted from Sanchi Ginseng, has been
      used for more than half a hundred years to treat coronary artery disease. The
      study is to establish a prediagnostic method for the hemolytic adverse effect of
      herbal medicine injection by taking Xue-Sai-Tong injection as an example.
      MATERIALS AND METHODS: A new method named "fuzzy dissemination" was established
      to identify the hemolytic ginsenosides in Xue-Sai-Tong injection on the basis of
      fuzzy changes of individual ginsenosides in the injections altered by re-adding
      the fractions prepared from the total saponins and statistic analysis between
      hemolytic degrees and individual ginsenosides. Related substances test, safety
      tests and fingerprints of the injections in different batches were tested.
      RESULTS: HD(50), P(50) and interactions on hemolysis of individual ginsenosides
      were examined. Experiment indicated that the content of Rg(1), Rg(2), M(51) (an
      unknown ingredient with retention time at 51 min in HPLC) and M(70) in Xue-Sai
      Tong injection showed a significant positive correlation with hemolytic degree,
      and the content of R(1), Re, Rb(1) and Rd showed a significant negative
      correlation with hemolytic activity. Furthermore HD(50) of injection exhibits
      superiority to other tests for the hemolysis of injections. Abnormal hemolysis in
      some batches of injections was observed, but there were no significant
      differences among injections of different batches in related substances test,
      safety test and fingerprints. CONCLUSIONS: This is an original method to analyze
      active ingredients of a complicated integrity instead of studying on individual
      ingredients, it showed that the interactions of some individual ginsenosides and
      some unknown micro-ingredients in Xue-Sai-Tong injection were the major factors
      causing hemolysis, and this method could also be utilized in research of
      corresponding aspects. HD(50) of injection can reflect the changes of hemolytic
      property of injections caused by not only the change of active constituents of
      injection, but also the auxiliary materials. Thus it was recommended as an index
      for the hemolytic prediagnosis of the injections in practice.

PMID- 21963557
TI  - Aqueous fraction from Costus spiralis (Jacq.) Roscoe leaf reduces contractility
      by impairing the calcium inward current in the mammalian myocardium.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Brazilian folk medicine uses infusion of Costus
      spiralis leaf to help people to treat arterial hypertension and syndromes of
      cardiac hyperexcitability. AIM OF THE STUDY: Evaluate the aqueous fraction (AqF)
      effect on atrial contractility and investigate its mechanism of action. MATERIALS
      AND METHODS: The AqF effect on the cardiac contractility was studied on isolated
      electrically driven guinea pig left atria. Atropine and tetraethylammonium (TEA)
      were employed to investigate whether potassium contributes for the inotropic
      mechanism of the AqF. The role of calcium in this effect was also studied. This
      was done by analysing the AqF effect on the Bowditch's phenomenon, as well as by
      studying whether it could interfere with the concentration-effect curve for
      CaCl(2), isoproterenol, and BAY K8644. Mice isolated cardiomyocytes were
      submitted to a whole-cell patch-clamp technique in order to evaluate whether the
      L-type calcium current participates on the AqF effect. Furthermore, the
      intracellular calcium transient was studied by confocal fluorescence microscopy.
      RESULTS: AqF depressed the atrial contractile force. It was the most potent
      fraction from C. spiralis leaf (EC(50)=305 +/- 41 mg/l) (crude extract:
      EC(50)=712 +/- 41; ethyl acetate: EC(50)=788 +/- 121; chloroform: EC(50)=8,948 +/
      1,346 mg/l). Sodium and potassium content in the AqF was 0.15 mM and 1.91 mM,
      respectively. Phytochemical analysis revealed phenols, tannins, flavones,
      xanthones, flavonoids, flavonols, flavononols, flavonones, and saponins.
      Experiments with atropine and TEA showed that potassium does not participate of
      the inotropic mechanism of AqF. However, this fraction decreased the force
      overshoot characteristic of the Bowditch's phenomenon, and shifted the
      concentration-response curve for CaCl(2) (EC(50) from 1.12 +/- 0.07 to 7.23 +/-
      0.47 mM) indicating that calcium currents participate on its mechanism of action.
      Results obtained with isoproterenol (1-1,000 pM) and BAY K8644 (5-2000nM) showed
      that AqF abolished the inotropic effect of these substances. On cardiomyocytes,
      48mg/l AqF reduced (~23%) the L-type calcium current density from -6.3 +/- 0.3 to
      -4.9 +/- 0.2 A/F (n=5 cells, p<0.05) and reduced the intracellular calcium
      transient (~20%, 4.7 +/- 1.2 a.u., n=42 cells to 3.7 +/- 1.00 a.u., n=35 cells,
      p<0.05). However, the decay time of the fluorescence was not changed (control:
      860 +/- 32 ms, n=42 cells; AqF: 876 +/- 26 ms, n=35 cells, p>0.05). CONCLUSIONS:
      The AqF of C. spiralis leaf depresses myocardial contractility by reducing the L
      type calcium current and by decreasing the intracellular calcium transient.
      Despite the lack of data on the therapeutic dose of AqF used in folk medicine,
      our results support, at least in part, the traditional use of this plant to treat
      cardiac disorders.

PMID- 21963558
TI  - Nitric oxide-dependent hypotensive effects of wax gourd juice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The wax gourd (Benincasa hispida (Thunb) Cong.)
      is a long-season vegetable that has been used in traditional Chinese medicine to
      treat high blood pressure. However, precise details of its effect and the
      mechanism of action involved are still lacking. MATERIALS AND METHODS: Ten-fold
      condensed wax gourd juice was used for the experiments. We measured (1) blood
      pressure of anesthetized normal Wistar rats in vivo, (2) isolated rat aortic
      contraction and relaxation, and (3) nitric oxide production from cultured porcine
      endothelial cells. The rats mentioned had not been treated with the
      investigational medicine. RESULTS: Intravenous injection of the juice produced a
      dose-dependent decrease in blood pressure. Treatment with the juice induced
      concentration-dependent relaxation of isolated rat aortic rings that had been
      precontracted with noradrenaline. The relaxation induced by the juice was
      strongly inhibited by treatment with the nitric oxide (NO) synthase inhibitor
      N(G)-nitro-l-arginine methyl ester hydrochloride (l-NAME) or endothelial
      denudation. Treatment with the juice produced NO from cultured porcine aortic
      endothelial cells. This NO production was significantly inhibited by l-NAME.
      CONCLUSIONS: The present findings suggest that wax gourd juice exerts a
      hypotensive effect via endothelium-dependent vasodilation. The main endothelium
      derived relaxing factor involved might be NO.

PMID- 21963559
TI  - Medicinal and therapeutic potential of Sea buckthorn (Hippophae rhamnoides L.).
AB  - ETHNOPHARMACOLOGICAL CONTEXT: This review explores the medicinal and therapeutic
      applications of Sea buckthorn (Hippophae rhamnoides L.) in curtailing different
      types of acute as well as chronic maladies. The plant is being used in different
      parts of the world for its nutritional and medicinal properties. MATERIALS AND
      METHODS: Sea buckthorn based preparations have been extensively exploited in
      folklore treatment of slow digestion, stomach malfunctioning, cardiovascular
      problems, liver injury, tendon and ligament injuries, skin diseases and ulcers.
      In the recent years, medicinal and pharmacological activities of Sea buckthorn
      have been well investigated using various in vitro and in vivo models as well as
      limited clinical trials. RESULTS: Sea buckthorn has been scientifically analyzed
      and many of its traditional uses have been established using several biochemical
      and pharmacological studies. Various pharmacological activities such as
      cytoprotective, anti-stress, immunomodulatory, hepatoprotective, radioprotective,
      anti-atherogenic, anti-tumor, anti-microbial and tissue regeneration have been
      reported. CONCLUSION: It is clear that Sea buckthorn is an important plant
      because of its immense medicinal and therapeutic potential. However, several
      knowledge gaps identified in this paper would give impetus to new academic and
      R&D activities especially for the development of Sea buckthorn based herbal
      medicine and nutraceuticals.

PMID- 21963560
TI  - Traditional phytotherapy remedies used in Southern Rwanda for the treatment of
      liver diseases.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Liver diseases represent a major health problem
      due to their complications and limited treatment possibilities. In Rwanda, given
      low accessibility to modern treatments, most people still rely on traditional
      medicinal plants. The symptomatology of many hepatic troubles (icterus) is
      evident for traditional healers who have a high probability of selecting
      efficient herbal medicines. OBJECTIVES: To document medicines used in the
      treatment of "hepatitis" in Southern Rwanda with the knowledge, attitudes and
      practices related to liver disorder recognition, control and treatment. MATERIALS
      AND METHODS: 56 traditional health practitioners, each a legal representative of
      an official association, were interviewed and participated in plant collection
      for the preparation of botanically identified herbarium specimens. RESULTS: 68
      multi-component and 65 single-component herbal recipes were identified for the
      treatment of liver diseases with a total of 86 different herbs from 34 families
      identified. The most represented were the Asteraceae and the Lamiaceae.
      Crassocephalum vitellinum, Hypoestes triflora and Erythrina abyssinica were the
      most widely used plants. The principle of polymedication for complex (i.e.
      multifactorial) diseases ("Ifumbi" in Rwanda), is a constant in every traditional
      practice. It is striking that the Rwandese therapy of liver diseases proposes so
      many single-herb preparations (49% of all herbal preparations). Some of the
      recorded plants or other species from the same genus have previously been
      documented for liver protection using various in vivo and in vitro models.
      CONCLUSION: Herbal remedies for hepatitis are widely used and highly diverse in
      Southern Rwanda; further chemical, pharmacological and toxicological studies are
      clearly required to rationally develop the most important remedies.

PMID- 21963561
TI  - Inhibitory effects of Chelidonium majus extract on atopic dermatitis-like skin
      lesions in NC/Nga mice.
AB  - AIM OF THE STUDY: Chelidonium majus (CM) has traditionally been used for
      treatment of various inflammatory diseases including atopic dermatitis (AD).
      However its action on atopic dermatitis (AD) is unclear. Therefore, we
      investigated the effect of CM on AD using NC/Nga mice as an AD model. MATERIALS
      AND METHODS: The effect of CM on 1-chloro-2,4-dinitrobenzene (DNCB) induced
      NC/Nga mice was evaluated by examining skin symptom severity, itching behavior,
      ear thickness, levels of serum immunoglobulin E (IgE), tumor necrosis factor
      alpha (TNF-alpha), and interlukin-4 (IL-4), skin histology. RESULTS: The CM
      significantly reduced the total clinical severity score, itching behavior, ear
      thickness and the level of serum IgE in AD mouse model. CM not only decreased TNF
      alpha but also IL-4. CONCLUSION: These results suggest that CM may be a potential
      therapeutic modality for AD.

PMID- 21963562
TI  - Helichrysum plicatum DC. subsp. plicatum extract as a preventive agent in
      experimentally induced urolithiasis model.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Since ancient times, various herbal preparations
      have been used in treatment of urolithiasis, which is basically formation of
      calcium oxalate stones in kidney. The aim of our study is to assess the effects
      of Helichrysum plicatum DC. subsp. plicatum (HP) as a preventive agent in
      experimentally induced urolithiasis model in rats. MATERIALS AND METHODS: The
      efficacy of 125, 250, and 500 mg/kg HP extract was studied in 1% ethylene glycol
      and 1% ammonium chloride-induced urolithiasis for 21 days in rats. The weight
      difference and the levels of calcium, magnesium, phosphorus, urea nitrogen,
      creatinine and uric acid in both serum and 24h-urine were measured. The calcium
      oxalate (CaOx) and pH were defined in urine. Histo-pathological analyses in
      kidneys were also performed. RESULTS: The rats' weights were higher in HP groups
      than urolithiasis group. Urolithiasis caused a significant increase in both serum
      and urine biochemical parameters compared to healthy rats. HP extract decreased
      levels of these parameters. Urine CaOx level was high in urolithiasis rats,
      whereas it was decreased by HP extract. Histopathological examinations revealed
      extensive intratubular crystal depositions and degenerative tubular structures in
      urolithiasis group, but not in HP treatment groups. CONCLUSION: More studies will
      be necessary to elucidate the antiurolithiatic activity of HP. Nonetheless,
      having a beneficial effect in preventing and eliminating CaOx deposition into
      kidneys, HP extract may be a potential drug for urolithiasis treatment.

PMID- 21963563
TI  - Total saponins of panax ginseng inhibiting human endothelium cells' damages
      induced by angiotensin II via AT1 receptor.
AB  - AIM OF THE STUDY: To investigate the effect and mechanism of total saponins of
      panax ginseng (TSPG) on the damages of endothelium cells induced by Angiotensin
      II (AngII). MATERIALS AND METHODS: Fifty SD rats were randomly divided into three
      groups: sham, AngII, and AngII+TSPG. The osmotic pumps with AngII were embedded
      in the backs of the animals in AngII and AngII+TSPG group, and TSPG was delivered
      through the gastric tube in AngII+TSPG group. The plasma tumor necrosis factor
      alpha (TNF-alpha) and nitric oxide (NO) were measured by ELISA, and Human aortic
      endothelial cells (HAECs) were observed with scanning electron microscope (SEM).
      In addition, HAECs were treated with AngII and TSPG or Ang-(1-7), and the ECs
      were incubated with AngII for 30min, before with AT1 receptor antagonist (AT1RA)
      and TSPG. Tested were NAD(P)H oxidase subunit P22phox mRNA, intracellular
      reactive oxidative species (ROS), nuclear factor-kappaB (NF-kappaB) and vascular
      cell adhesion molecule-1(VCAM) expression. RESULTS: In the in vivo study, the
      plasma TNF-alpha increased significantly in AngII group when compared with the
      sham group, and decreased significantly in AngII+TSPG group. However, NO
      measurement produced opposite results. The surface of the thoracic aorta ECs
      desquamated in the AngII group, and most of them were restored in the AngII+TSPG
      group. In the in vitro study, TSPG reduced significantly the expressions of the
      NAD(P)H oxidize subunit P22phox, NF-kappaB and intracellular ROS production
      induced by AngII, and the inhibitory effects of TSPG were partially blocked by
      AT1 receptor antagonist. CONCLUSION: TSPG was found to be capable of preventing
      the damages of ECs induced by Ang II via AT1 receptor pathway.

PMID- 21963564
TI  - Liver triacylglycerol lipases.
AB  - The hallmark of obesity and one of the key contributing factors to insulin
      resistance, type 2 diabetes and cardiovascular disease is excess triacylglycerol
      (TG) storage. In hepatocytes, excessive accumulation of TG is the common
      denominator of a wide range of clinicopathological entities known as nonalcoholic
      fatty liver disease, which can eventually progress to cirrhosis and associated
      complications including hepatic failure, hepatocellular carcinoma and death. A
      tight regulation between TG synthesis, hydrolysis, secretion and fatty acid
      oxidation is required to prevent lipid accumulation as well as lipid depletion
      from hepatocytes. Therefore, understanding the pathways that regulate hepatic TG
      metabolism is crucial for development of therapies to ameliorate
      pathophysiological conditions associated with excessive hepatic TG accumulation,
      including dyslipidemias, viral infection and atherosclerosis. This review
      highlights the physiological roles of liver lipases that degrade TG in cytosolic
      lipid droplets, endoplasmic reticulum, late endosomes/lysosomes and along the
      secretory route. This article is part of a Special Issue entitled Triglyceride
      Metabolism and Disease.

PMID- 21963565
TI  - P-glycoprotein and its inhibition in tumors by phytochemicals derived from
      Chinese herbs.
AB  - P-glycoprotein belongs to the family of ATP-binding cassette (ABC) transporters.
      It functions in cellular detoxification, pumping a wide range of xenobiotic
      compounds, including anticancer drugs out of the cell. In cancerous cells, P
      glycoprotein confers resistance to a broad spectrum of anticancer agents, a
      phenomenon termed multidrug resistance. An attractive strategy for overcoming
      multidrug resistance is to block the transport function of P-glycoprotein and
      thus increase intracellular concentrations of anticancer drugs to lethal levels.
      Efforts to identify P-glycoprotein inhibitors have led to numerous candidates,
      none of which have passed clinical trials with cancer patients due to their high
      toxicity. The search for naturally inhibitory products from traditional Chinese
      medicine may be more promising because natural products are frequently less toxic
      than chemically synthesized substances. In this review, we give an overview of
      molecular and clinical aspects of P-glycoprotein and multidrug resistance in the
      context of cancer as well as Chinese herbs and phytochemicals showing inhibitory
      activity towards P-glycoprotein.

PMID- 21963566
TI  - Resilience and adaptation in the use of medicinal plants with suspected anti
      inflammatory activity in the Brazilian Northeast.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: This study uses the utilitarian redundancy model
      as a basis to investigate issues related to the preference for plants native to
      the Caatinga used as anti-inflammatories by respondents from the community of
      Carao in rural Pernambuco, Brazil. MATERIALS AND METHODS: For this purpose, 49
      respondents and 24 native plants used as anti-inflammatories were selected from a
      database built by previous studies in this study area. Interviews with
      respondents were conducted by applying the checklist-interview technique and by
      presenting photographs of plants, which were ordered according to plant
      preference for each type of inflammation mentioned. After elaborating each list
      of preferences, we inquired as to the criteria used for the construction of the
      lists. A salience index was calculated to determine the most- and least-preferred
      species, and principal component analysis (PCA) was used to identify the most
      significant criteria used by the respondents to indicate the preferred plants for
      anti-inflammatory use. RESULTS: We identified 37 subcategories or inflammatory
      conditions, most of which were associated with disorders of the genitourinary (8
      conditions), digestive (7) and respiratory (4) systems. Subcategories with the
      highest level of redundancy include "wound" (79.1% of species), "cut" (66.6%) and
      "uterus" (66.6%), and five non-redundant conditions were identified (only one
      species). We obtained approximately 300 lists and 18 choice criteria. PCA
      analysis showed that seven species were most preferred by the respondents, as
      they showed the highest salience values, and that the preferred criterion was
      "treatment effectiveness". CONCLUSIONS: These results indicate that inflammation
      is a complex collection of disorders consisting of several subcategories.
      Furthermore, respondents preferred different treatments for different
      inflammatory conditions, which pose a challenge for future pharmacological
      studies that aim to assess the biological activity of anti-inflammatory plants.
      Preferences were very specific, focused on a small number of species and mainly
      related to therapeutic effectiveness.

PMID- 21963567
TI  - Tracheal relaxation of five Ivorian anti-asthmatic plants: role of epithelium and
      K+ channels in the effect of the aqueous-alcoholic extract of Dichrostachys
      cinerea root bark.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Leaves of Boerhavia diffusa (Nyctaginaceae),
      Baphia nitida, Cassia occidentalis, Desmodium adscendens (Fabaceae), and root
      bark of Dichrostachys cinerea (Fabaceae) are used in Ivory Coast for the
      treatment of asthma. The aim of this study was to evaluate the potential airway
      relaxant activity of different extracts of these plants. MATERIALS AND METHODS:
      Extracts of different polarities (H(2)O, EtOH/H(2)O, MeOH and CH(2)Cl(2)) were
      obtained from these five plants. Their ex vivo relaxant activity was tested in
      mice isolated trachea precontracted with carbachol (1 MUM). RESULTS: Cumulative
      concentrations of most extracts induced moderate to strong relaxation, the
      methanolic extracts being the most potent and the polar extracts the most active
      at the concentrations used, supporting the traditional use of these five plants
      as anti-asthmatic remedies. We further investigated the molecular and cellular
      mechanisms of the mouse trachea relaxant effect of the aqueous-alcoholic extract
      of Dichrostachys cinerea root bark, the most potent extract. Its effect was not
      modified in the presence of beta-adrenoceptor antagonists (propranolol or ICI
      118,551) or a PKA inhibitor (H89). By contrast, it was decreased after
      depolarization-induced precontraction (with 80 mM KCl), in the presence of some
      K(+) channels blockers [4-aminopyridine as voltage-dependent K(+) (K(v)) channel
      blocker and tetraethylammonium chloride as large conductance Ca(2+)-activated
      K(+) (BK(Ca)) channel blocker, but not with glibenclamide, an ATP-sensitive K(+)
      (K(ATP)) channel blocker] or after epithelium removal. CONCLUSIONS: The mouse
      tracheal relaxant effect of Dichrostachys cinerea EtOH/H(2)O extract was
      independent of beta(2)-adrenoceptors activation and cAMP/PKA pathway, but
      dependent on epithelium and K(+) channels, namely K(v) and BK(Ca) channels.
      Further investigation will be required to identify the component(s) responsible
      for this airways relaxant activity.

PMID- 21963568
TI  - Zootherapeutic practices in Aquismon, San Luis Potosi, Mexico.
AB  - ETHNOPHARMACOLOGICAL IMPORTANCE: Animal derived products have been a source of
      medicinal compounds since ancient times. This work documents the use of animal
      species in traditional medicine in the municipality of Aquismon, San Luis Potosi,
      Mexico. MATERIALS AND METHODS: Direct interviews were performed with inhabitants
      from Aquismon. The interviews were analyzed with two quantitative tools: (a) the
      informant consensus (ICF) that estimates the level of agreement about which
      animals may be used for each category and (b) the relative importance (RI) that
      determines the extent of potential utilization of each species. RESULTS: A total
      of 24 animal species used for medicinal purposes, belonging to 22 families and 4
      taxonomic categories, were reported by interviewees. Nine medicinal species had
      not been reported in scientific literature. The results of the IFC showed that
      diseases of the respiratory systems had the greatest agreement. The most
      versatile species according to their RI are Crotalus atrox and Mephitis macroura.
      CONCLUSION: Further studies with medicinal fauna from Aquismon are required for
      the experimental validation of their traditional uses, especially with Mephitis
      macroura and Crotalus atrox.

PMID- 21963569
TI  - Baicalein, isolated from Scutellaria baicalensis, protects against endothelin-1
      induced pulmonary artery smooth muscle cell proliferation via inhibition of TRPC1
      channel expression.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: We investigated the antiproliferative effects of
      baicalein, isolated from Scutellaria baicalensis (Huang-qin), on ET-1-mediated
      pulmonary artery smooth muscle cells (PASMCs) proliferation and the mechanisms
      underlying these effects. MATERIALS AND METHODS: Intrapulmonary artery smooth
      muscle cells were isolated and cultured from female Sprague-Dawley rats and used
      during passages 3-6. The proliferation of PASMCs was quantified by cell counting
      and XTT assay. The protein expression of TRPC1 and PKCalpha were determined by
      western blotting. The cell cycle pattern was assayed by flow cytometry. The
      intracellular calcium concentrations ([Ca(2+)](i)) were measured using the
      fluorescent indicator fura-2-AM and flow cytometry. RESULTS: Baicalein (0.3-3
      MUM) inhibited PASMCs proliferation, promoted cell cycle progression, enhanced
      [Ca(2+)](i) levels, increased capacitative Ca(2+) entry (CCE), upregulated the
      canonical transient receptor potential 1 (TRPC1) channel and membrane protein
      kinase Calpha (PKCalpha) expression induced by ET-1 (0.1 MUM). The PKC activator
      PMA (1 MUM) reversed the inhibitory effects of baicalein on ET-1-induced
      upregulation of TRPC1 expression and S phase accumulation, while the PKC
      inhibitor chelerythrine (1 MUM) potentiated baicalein-mediated G(2)/M phase
      arrest and TRPC1 channel inhibition. CONCLUSION: Our findings suggest that
      baicalein protects against ET-1-induced PASMCs proliferation via modulation of
      the PKC-mediated TRPC channel.

PMID- 21963570
TI  - Matrix metalloproteinase-9 for the earliest stage acute coronary syndrome.
AB  - BACKGROUND: Matrix metalloproteinase-9 (MMP-9) is regarded as a biomarker of
      plaque rupture or vulnerability and is elevated in patients with acute coronary
      syndrome (ACS). The aim of the present study was to evaluate the diagnostic value
      of MMP-9 for early ACS (<=4h of onset) and late ACS (>4h after onset), compared
      with high-sensitivity troponin T (hs-TnT). METHODS AND RESULTS: MMP-9 and hs-TnT
      were measured in 200 patients with ST elevation ACS (STEACS; 115 early STEACS and
      85 late STEACS patients), and 66 patients with non-ST elevation ACS (NSTEACS; 25
      early NSTEACS and 41 late NSTEACS patients). Forty patients with stable angina
      pectoris (SAP) were enrolled as a control group. MMP-9 levels were significantly
      higher in patients with early STEACS (P<0.001), early NSTEACS (P<0.001), late
      STEACS (P<0.001) and late NSTEACS (P=0.025) than SAP. MMP-9 levels were
      significantly higher in patients with early STEACS (P=0.017) and early NSTEACS
      (P=0.034) than late STEACS and late NSTEACS, respectively. Levels of hs-TnT were
      significantly lower in patients with early STEACS (P<0.001) and early NSTEACS
      (P=0.007) than late STEACS and late NSTEACS, respectively. On receiver operating
      characteristic curve analysis, area under the curve of early STEACS, early
      NSTEACS, late STEACS and late NSTEACS was 0.880, 0.782, 0.790 and 0.648 for MMP
      9, and 0.707, 0.725, 0.993 and 0.920 for hs-TnT, respectively. CONCLUSIONS: MMP-9
      levels were elevated earlier than hs-TnT and had a higher diagnostic value for
      early ACS, but not for late ACS, reflecting plaque rupture or vulnerability.

PMID- 21963571
TI  - Pulmonary arterial hypertension associated with connective tissue disease and
      immunosuppressive therapy.

PMID- 21963572
TI  - Evaluation of circulating endothelial progenitor cells in cardiovascular risk.

PMID- 21963573
TI  - Making a splash? -Intrathoracic impedance and the prediction of arrhythmic
      events.-.

PMID- 21963574
TI  - Resolving strain in carbon nanotubes at the atomic level.
AB  - Details of how atomic structure responds to strain are essential for building a
      deeper picture of mechanics in nanomaterials. Here, we provide the first
      experimental evidence of atomic displacements associated with shear strain in
      single-walled carbon nanotubes (SWNTs) by direct imaging using aberration
      corrected transmission electron microscopy. The atomic structure of a zig-zag
      SWNT is resolved with unprecedented accuracy and the strain induced by bending is
      mapped in two dimensions. We show the existence of a dominant non-uniform shear
      strain that varies along the SWNT axis. The direction of shear is opposite to
      what would be expected from a simple force applied perpendicular to the axis to
      produce the bending. This highlights the complex atomistic strain behaviour of
      beam-bending mechanics in highly anisotropic SWNTs.

PMID- 21963575
TI  - A novel experimental in vivo model of cerebral immunomodulation induced by
      inactivated Staphylococcus epidermidis.
AB  - The genesis and appropriate treatment of neuroinflammation in various infectious
      and non-infectious disorders of the central nervous system is still a matter of
      debate. We introduce an alternative and simple experimental model for the
      investigation of the cellular inflammatory response to bacterial antigens by
      stereotactic intracerebral injection of heat-inactivated Staphylococcus
      epidermidis (HISE). HISE-injection resulted in well-circumscribed
      intraparenchymal deposits encompassed by an early micro- and astroglial response
      and a selective but sustained opening of the blood-brain barrier (BBB). After
      24h, the HISE collections were densely infiltrated by granulocytes and few
      circumjacent macrophages that became the predominating immunocompetent cell type
      from day 4 on. CD8a+ lymphocytes peaked at day 4, whereas CD4+ and CD20+
      lymphocytes increased gradually in number, developing a scattered infiltrate
      until day 17, indicating the initiation of an adaptive immune response. MHC class
      II presenting cells were abundantly recruited from day 1 and eventually shaped an
      increasingly dense accumulation within the lesion. Intracerebral HISE
      administration provides a controlled, highly reproducible and well defined influx
      of immunocompetent cells across the BBB leading to a distinct and condensed
      inflammatory reaction. The technique is straightforward, easily feasible and may
      significantly enable further investigations of the initiation, maintenance and
      therapeutic modulation of acute neuroinflammation.

PMID- 21963576
TI  - Understanding neuronal systems in movement control using Wiener/Volterra kernels:
      a dominant feature analysis.
AB  - Although Volterra kernels have been extensively applied in modelling and analysis
      of biological systems, the relationship between the kernel characteristics and
      physiologically important features under study is still not revealed clearly. In
      this study, the link between Volterra kernels and dynamic response of neural
      systems which control animal movements was investigated and demonstrated using a
      dominant feature analysis. The new results show an effective but simplified
      method to use Volterra or Wiener kernels to understand and classify the neural
      systems which are responsible for the fundamental movements such as flexion and
      extension of animal limbs, and importantly demonstrate how the neuron pathways in
      locusts control joint activities of low and high frequency and perform
      fundamental joint movements such as position, velocity and acceleration. These
      results provide a useful insight into the nonlinear characteristics of neural
      systems in movement control and show a useful approach to the analysis of
      physiological systems using Volterra/Wiener kernels.

PMID- 21963577
TI  - Clinical characteristics and epidemiology of pulmonary pseudallescheriasis.
AB  - BACKGROUND: Some members of the Pseudallescheria (anamorph Scedosporium) have
      emerged as an important cause of life-threatening infections in humans. These
      fungi may reach the lungs and bronchial tree causing a wide range of
      manifestations, from colonization of airways to deep pulmonary infections.
      Frequently, they may also disseminate to other organs, with a predilection for
      the brain. In otherwise healthy patients, the infection is characterized by non
      invasive type involvement, while invasive and/or disseminated infections were
      mostly seen in immunocompromised patients. AIMS: We reviewed all the available
      reports on Pseudallescheria/Scedosporium pulmonary infections, focusing on the
      geographical distribution, immune status of infected individuals, type of
      infections, clinical manifestations, treatment and outcome. RESULTS AND
      CONCLUSIONS: The main clinical manifestations of the 189 cases of pulmonary
      pseudallescheriasis reviewed were pneumonia (89), followed by fungus ball (26),
      and chest abscess (18). Some patients had more than one type of invasive
      pulmonary manifestations. Among patients with pneumonia, several cases of
      pneumonia associated with near-drowning (10/89, 11.2%) have also been reported in
      immunocompetent hosts. Major underlying conditions for non-invasive pulmonary
      infection were preexisting lung cavities and medical immunosuppression for
      invasive pulmonary infection. Saprobic airway colonization was mostly seen in
      patients with mucosal dysfunction, i.e. patients with cystic fibrosis. The
      mortality rate was closely related to the infection type, being 26.8% in non
      invasive type (fungus balls) and 57.2% in invasive type.

PMID- 21963578
TI  - Effects of levosimendan on mortality and hospitalization. A meta-analysis of
      randomized controlled studies.
AB  - OBJECTIVE: Catecholaminergic inotropes have a place in the management of low
      output syndrome and decompensated heart failure but their effect on mortality is
      debated. Levosimendan is a calcium sensitizer that enhances myocardial
      contractility without increasing myocardial oxygen use. A meta-analysis was
      conducted to determine the impact of levosimendan on mortality and hospital stay.
      DATA SOURCES: BioMedCentral, PubMed, Embase, and the Cochrane Central Register of
      clinical trials were searched for pertinent studies. International experts and
      the manufacturer were contacted. STUDY SELECTION: Articles were assessed by four
      trained investigators, with divergences resolved by consensus. Inclusion criteria
      were random allocation to treatment and comparison of levosimendan vs. control.
      There were no restrictions on dose or time of levosimendan administration or on
      language. Exclusion criteria were: duplicate publications, nonadult studies, oral
      administration of levosimendan, and no data on main outcomes. DATA EXTRACTION:
      Study end points, main outcomes, study design, population, clinical setting,
      levosimendan dosage, and treatment duration were extracted. DATA SYNTHESIS: Data
      from 5,480 patients in 45 randomized clinical trials were analyzed. The overall
      mortality rate was 17.4% (507 of 2,915) among levosimendan-treated patients and
      23.3% (598 of 2,565) in the control group (risk ratio 0.80 [0.72; 0.89], p for
      effect <.001, number needed to treat = 17 with 45 studies included). Reduction in
      mortality was confirmed in studies with placebo (risk ratio 0.82 [0.69; 0.97], p
      = .02) or dobutamine (risk ratio 0.68 [0.52-0.88]; p = .003) as comparator and in
      studies performed in cardiac surgery (risk ratio 0.52 [0.35; 0.76] p = .001) or
      cardiology (risk ratio 0.75 [0.63; 0.91], p = .003) settings. Length of hospital
      stay was reduced in the levosimendan group (weighted mean difference = -1.31 [
      1.95; -0.31], p for effect = .007, with 17 studies included). A trend toward a
      higher percentage of patients experiencing hypotension was noted in levosimendan
      vs. control (risk ratio 1.39 [0.97-1.94], p = .053). CONCLUSIONS: Levosimendan
      might reduce mortality in cardiac surgery and cardiology settings of adult
      patients.

PMID- 21963579
TI  - Early type II fiber atrophy in intensive care unit patients with nonexcitable
      muscle membrane.
AB  - OBJECTIVE: Intensive care unit-acquired weakness indicates increased morbidity
      and mortality. Nonexcitable muscle membrane after direct muscle stimulation
      develops early and predicts intensive care unit-acquired weakness in sedated,
      mechanically ventilated patients. A comparison of muscle histology at an early
      stage in intensive care unit-acquired weakness has not been done. We investigated
      whether nonexcitable muscle membrane indicates fast-twitch myofiber atrophy
      during the early course of critical illness. DESIGN: Prospective observational
      study. SETTING: Two intensive care units at Charite University Medicine, Berlin.
      PATIENTS: Patients at increased risk for development of intensive care unit
      acquired weakness, indicated by Sepsis-related Organ Failure Assessment scores
      >=8 on 3 of 5 consecutive days within their first week in the intensive care
      unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Electrophysiological
      compound muscle action potentials after direct muscle stimulation and muscle
      biopsies were obtained at median days 7 and 5, respectively. Patients with
      nonexcitable muscle membranes (n = 15) showed smaller median type II cross
      sectional areas (p < .05), whereas type I muscle fibers did not compared with
      patients with preserved muscle membrane excitability (compound muscle action
      potentials after direct muscle stimulation >=3.0 mV; n = 9). We also observed
      decreased mRNA transcription levels of myosin heavy chain isoform IIa and a lower
      densitometric ratio of fast-to-slow myosin heavy chain protein content.
      CONCLUSION: We suggest that electrophysiological nonexcitable muscle membrane
      predicts preferential type II fiber atrophy in intensive care unit patients
      during early critical illness.

PMID- 21963580
TI  - Neglect of quality-of-life considerations in intensive care unit family meetings
      for long-stay intensive care unit patients.
AB  - OBJECTIVE: To examine the frequency with which quality of life and treatment
      limitation were discussed in formal family meetings for long-stay intensive care
      unit patients with high risk for mortality and morbidity. DESIGN: Descriptive
      observational study. SETTING: Five intensive care units. PATIENTS: One hundred
      sixteen family surrogate decisionmakers of long-stay intensive care unit patients
      who participated in an intensive communication system that aimed to provide
      weekly meetings with family decisionmakers. The structure of each meeting was to
      address medical update, patient preferences, treatment plan, and milestones for
      evaluating the treatment plan. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: We audiotaped initial family meetings for 116 family decisionmakers for
      a total of 180 meetings. On average, meetings were 24 mins long with a majority
      of time being devoted to nonemotional speech and little (12%) spent discussing
      patient preferences. Quality of life was discussed in 45% and treatment
      limitation in 23% of all meetings. Quality-of-life discussions were more likely
      to occur when patients were admitted to a medical intensive care unit (odds ratio
      [OR] 5.9; p = .005), have a family decisionmaker who is a spouse (OR 9.4; p =
      .0001), were older (OR 1.04; p = 01), have a shorter length of stay (OR 0.93; p =
      .001), and have a family decisionmaker who was a spouse (OR 5.1; p = .002). For
      those with a treatment limitation discussion, 67% had a do-not-resuscitate order,
      40% were admitted to a medical intensive care unit, 56% had a family
      decisionmaker who had been their caregiver, and 48% of their family
      decisionmakers were their children. CONCLUSIONS: To guide discussion with
      families of the subset of intensive care unit patients with high risk of
      mortality and long-term morbidity, quality of life was not consistently
      addressed. Continued efforts to assist clinicians in routinely including
      discussions of quality-of-life outcomes is needed.

PMID- 21963581
TI  - A multifaceted program for improving quality of care in intensive care units:
      IATROREF study.
AB  - OBJECTIVE: To test the effects of three multifaceted safety programs designed to
      decrease insulin administration errors, anticoagulant prescription and
      administration errors, and errors leading to accidental removal of endotracheal
      tubes and central venous catheters, respectively. Medical errors and adverse
      events are associated with increased mortality in intensive care patients,
      indicating an urgent need for prevention programs. DESIGN: Multicenter cluster
      randomized study. SETTING: One medical intensive care unit in a university
      hospital and two medical-surgical intensive care units in community hospitals
      belonging to the Outcomerea Study Group. PATIENTS: Consecutive patients >18 yrs
      admitted from January 2007 to January 2008 to the intensive care units.
      INTERVENTIONS: We tested three multifaceted safety programs vs. standard care in
      random order, each over 2.5 months, after a 1.5-month observation period.
      MEASUREMENTS AND MAIN RESULTS: Incidence rates of medical errors/1000 patient
      days in the multifaceted safety program and standard-care groups were compared
      using adjusted hierarchical models. In 2117 patients with 15,014 patient-days,
      8520 medical errors (567.5/1000 patient-days) were reported, including 1438
      adverse events (16.9%, 95.8/1000 patient-days). The insulin multifaceted safety
      program significantly decreased errors during implementation (risk ratio 0.65;
      95% confidence interval [CI] 0.52-0.82; p = .0003) and after implementation (risk
      ratio 0.51; 95% CI 0.35-0.73; p = .0004). A significant Hawthorne effect was
      found. The accidental tube/catheter removal multifaceted safety program decreased
      errors significantly during implementation (odds ratio [OR] 0.34; 95% CI 0.15
      0.81; p = .01]) and nonsignificantly after implementation (OR 1.65; 95% CI 0.78
      3.48). The anticoagulation multifaceted safety program was not significantly
      effective (OR 0.64; 95% CI 0.26-1.59) but produced a significant Hawthorne
      effect. CONCLUSIONS: A multifaceted program was effective in preventing insulin
      errors and accidental tube/catheter removal. Significant Hawthorne effects
      occurred, emphasizing the need for appropriately designed studies before
      definitively implementing strategies. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00461461.

PMID- 21963582
TI  - Hospitalizations, costs, and outcomes of severe sepsis in the United States 2003
      to 2007.
AB  - OBJECTIVES: To assess trends in number of hospitalizations, outcomes, and costs
      of severe sepsis in the United States. DESIGN: Temporal trends study using the
      Nationwide Inpatient Sample. PATIENTS: Adult patients with severe sepsis (defined
      as a diagnosis of sepsis and organ dysfunction) diagnosed between 2003 and 2007.
      MEASUREMENTS AND MAIN RESULTS: We determined the weighted frequency of patients
      hospitalized with severe sepsis. We calculated age- and sex-adjusted population
      based mortality rates for severe sepsis per 100,000 population and also used
      logistic regression to adjust in-hospital mortality rates for patient
      characteristics. We calculated inflation-adjusted costs using hospital-specific
      cost-to-charge ratios. We identified a rapid steady increase in the number of
      cases of severe sepsis, from 415,280 in 2003 to 711,736 in 2007 (a 71% increase).
      The total hospital costs for all patients with severe sepsis increased from $15.4
      billion in 2003 to $24.3 billion in 2007 (57% increase). The proportion of
      patients with severe sepsis and only a single organ dysfunction decreased from
      51% in 2003 to 45% in 2007 (p < .001), whereas the proportion of patients with
      three or four or more organ dysfunctions increased 1.19-fold and 1.51-fold,
      respectively (p < .001). During the same time period, we observed 2% decrease per
      year in hospital mortality for patients with severe sepsis (p < .001), as well as
      a slight decrease in the length of stay (9.9 days to 9.2 days; p < .001) and a
      significant decrease in the geometric mean cost per case of severe sepsis
      ($20,210 per case in 2003 and $19,330 in 2007; p = .025). CONCLUSIONS: The
      increase in the number of hospitalizations for severe sepsis coupled with
      declining in-hospital mortality and declining geometric mean cost per case may
      reflect improvements in care or increases in discharges to skilled nursing
      facilities; however, these findings more likely represent changes in
      documentation and hospital coding practices that could bias efforts to conduct
      national surveillance.

PMID- 21963583
TI  - Impact of resuscitation system errors on survival from in-hospital cardiac
      arrest.
AB  - BACKGROUND: An estimated 350,000-750,000 adult, in-hospital cardiac arrest (IHCA)
      events occur annually in the United States. The impact of resuscitation system
      errors on survival during IHCA resuscitation has not been evaluated. The purpose
      of this paper was to evaluate the impact of resuscitation system errors on
      survival to hospital discharge after IHCA. METHODS AND RESULTS: We evaluated
      subjective and objective errors in 118,387 consecutive, adult, index IHCA cases
      entered into the Get with the Guidelines National Registry of Cardiopulmonary
      Resuscitation database from January 1, 2000 through August 26, 2008. Cox
      regression analysis was used to determine the relationship between reported
      resuscitation system errors and other important clinical variables and the hazard
      ratio for death prior to hospital discharge. Of the 108,636 patients whose
      initial IHCA rhythm was recorded, resuscitation system errors were committed in
      9,894/24,467 (40.4%) of those with an initial rhythm of ventricular fibrillation
      or pulseless ventricular tachycardia (VF/pVT) and in 22,599/84,169 (26.8%) of
      those with non-VF/pVT. The most frequent system errors related to delay in
      medication administration (>5 min time from event recognition to first dose of a
      vasoconstrictor), defibrillation, airway management, and chest compression
      performance errors. The presence of documented resuscitation system errors on an
      IHCA event was associated with decreased rates of return of spontaneous
      circulation, survival to 24h, and survival to hospital discharge. The relative
      risk of death prior to hospital discharge based on hazard ratio analysis was 9.9%
      (95% CI 7.8, 12.0) more likely for patients whose initial documented rhythm was
      non-VF/pVT when resuscitation system errors were reported compared to when no
      errors were reported. It was 34.2% (95% CI 29.5, 39.1) more likely for those with
      VF/pVT. CONCLUSIONS: The presence of resuscitation system errors that are evident
      from review of the resuscitation record is associated with decreased survival
      from IHCA in adults. Hospitals should target the training of first responders and
      code team personnel to emphasize the importance of early defibrillation, early
      use of vasoconstrictor medication, and compliance with ACLS protocols.

PMID- 21963584
TI  - Mobile phones-their increasing role in education and implementation of CPR.

PMID- 21963585
TI  - Focus on molecules: Brg1: a range of functions during eye development.

PMID- 21963586
TI  - A novel functional assay for fungal histidine kinases group III reveals the role
      of HAMP domains for fungicide sensitivity.
AB  - Signal transduction systems comprising histidine kinases are suggested as new
      molecular targets of antibiotics. The important human fungal pathogen Candida
      albicans possesses three histidine kinases, one of which is the type III
      histidine kinase CaNik1, which activates the MAP kinase Hog1. We established a
      screening system for inhibitors of this class of histidine kinases by functional
      expression of the CaNIK1 gene in S. cerevisiae. This transformant was susceptible
      to fungicides to which the wild type strain was resistant, such as fludioxonil
      and ambruticin. Growth inhibition correlated with phosphorylation of Hog1 and was
      dependent on an intact Hog1 pathway. At the N-terminus the histidine kinase
      CaNik1 has four amino acid repeats of 92 amino acids each and one truncated
      repeat of 72 amino acids. Within these repeats we identified 9 HAMP domains with
      a paired structure. We constructed mutants in which one or two pairs of these
      domains were deleted. S. cerevisiae transformants expressing the full-length
      CaNIK1 showed the highest sensitivity to the fungicides, any truncation reduced
      the susceptibility of the transformants to the fungicides. This indicates that
      the HAMP domains are decisive for the mode of action of the antifungal compounds.

PMID- 21963587
TI  - Reference gene validation for qPCR on normoxia- and hypoxia-cultured human dermal
      fibroblasts exposed to UVA: is beta-actin a reliable normalizer for photoaging
      studies?
AB  - Data normalization of gene expression on human dermal fibroblasts (HDF) exposed
      to UVA has commonly been done using either GAPDH or beta-actin as reference genes
      without any validation of their expression stability. Since this aspect,
      important for accurate normalization, has been overlooked, we aimed to establish
      a suitable set of reference genes for studies on UVA-treated HDF cultured under
      both standard atmospheric oxygen tension (normoxia, 21%) and under a
      physiological, low oxygen tension for these cells (hypoxia, 5%). The stability of
      six commonly used reference genes was assessed using the geNorm and NormFinder
      softwares subsequent to reverse-transcription quantitative real-time PCR (RT
      qPCR). GAPDH/SDHA were found to be the most stable genes under normoxia, while
      SDHA/TBP or HPRT1/beta2M were the most stable ones under hypoxia in HDF exposed
      to 18 J/cm(2) UVA. beta-Actin was always the most unstable reference gene. To
      emphasize the importance of selecting the most stably expressed reference genes
      for obtaining reliable results, mRNA expression levels of MMP-1 and COL1A1 were
      analyzed vs the best reference genes and the worst one. These reference genes are
      hence recommended for future qPCR analyses in studies concerning photo-damage on
      UVA-treated HDF.

PMID- 21963588
TI  - Controlling rice bacterial blight in Africa: needs and prospects.
AB  - Rice cultivation has drastically increased in Africa over the last decade. During
      this time, the region has also seen a rise in the incidence of rice bacterial
      blight caused by the pathogen Xanthomonas oryzae pv. oryzae. The disease is
      expanding to new rice production areas and threatens food security in the region.
      Yield losses caused by X. oryzae pv. oryzae range from 20 to 30% and can be as
      high as 50% in some areas. Employing resistant cultivars is the most economical
      and effective way to control this disease. To facilitate development and
      strategic deployment of rice cultivars with resistance to bacterial blight,
      biotechnology tools and approaches, including marker-assisted breeding, gene
      combinations for disease control, and multiplex-PCR for pathogen diagnosis, have
      been developed. Although these technologies are routinely used elsewhere, their
      application in Africa remains limited, usually due to high cost and advanced
      technical skills required. To combat this problem, developers of the technologies
      at research institutions need to work with farmers from an early stage to create
      and promote the integration of successful, low cost applications of research
      biotech products. Here, we review the current knowledge and biotechnologies
      available to improve bacterial blight control. We will also discuss how to
      facilitate their application in Africa and delivery to the field.

PMID- 21963589
TI  - Protein-encapsulated bio-nanocapsules production with ER membrane localization
      sequences.
AB  - Bio-nanocapsules (BNCs) are hollow nanoparticles composed of the L protein of
      hepatitis B virus (HBV) surface antigen (HBsAg), which can specifically introduce
      genes and drugs into various kinds of target cells. Although the classic
      electroporation method has typically been used to introduce highly charged
      molecules such as DNA, it is rarely adopted for proteins due to its very low
      efficiency. In this study, a novel approach to the preparation of BNC was
      established whereby a target protein was pre-encapsulated during the course of
      nanoparticle formation. Briefly, because of the process of BNC formation in a
      budding manner on the endoplasmic reticulum (ER) membrane, the association of
      target proteins to the ER membrane with lipidation sequences (ER membrane
      localization sequences) could directly generate protein-encapsulating BNC in
      collaboration with co-expression of the L proteins. Since the membrane-localized
      proteins are automatically enveloped into BNCs during the budding event, this
      method can be protect the proteins and BNCs from damage caused by electroporation
      and obviate the need for laborious consideration to study the optimal conditions
      for protein encapsulation. This approach would be a useful method for
      encapsulating therapeutic candidate proteins into BNCs.

PMID- 21963590
TI  - Fermentative glycolysis with purified Escherichia coli enzymes for in vitro ATP
      production and evaluating an engineered enzyme.
AB  - Each of the twelve enzymes for glycolytic fermentation, eleven from Escherichia
      coli and one from Saccharomyces cerevisiae, have been over-expressed in E. coli
      and purified with His-tags. Simple assays have been developed for each enzyme and
      they have been assembled for fermentation of glucose to ethanol. Phosphorus-31
      NMR revealed that this in vitro reaction accumulates fructose 1,6-bisphosphate
      while recycling the cofactors NAD(+) and ATP. This reaction represents a defined
      ATP-regeneration system that can be tailored to suit in vitro biochemical
      reactions such as cell-free protein synthesis. The enzyme from S. cerevisiae,
      pyruvate decarboxylase 1 (Pdc1; EC 4.1.1.1), was identified as one of the major
      'flux controlling' enzymes for the reaction and was replaced with an evolved
      version of Pdc1 that has over 20-fold greater activity under glycolysis reaction
      conditions. This substitution was only beneficial when the ratio of glycolytic
      enzymes was adjusted to suit greater Pdc1 activity.

PMID- 21963591
TI  - Different strategies of mixed chimerism induction may determine stem/progenitor
      cell populations in recipient mice.
AB  - Mixed chimerism has been suggested to induce tolerance to transplanted
      alloantigens. As the precise influence of mixed chimerism induction on the host
      organism has still not been fully elucidated, the aim of the present study was to
      explore this phenomenon in relation to the stem cell compartment. The experiment
      was performed on B6.SJL-Ptprc(a)Pep3(b) mice. Mixed chimerism induction protocols
      involved 3 Gy TBI (Day -1 of the experiment), injection of 20-30 * 10(6) Balb C
      bone marrow cells (Day 0), and administration of blocking antibodies against
      CD40L (Day 0 and Day 4), anti-CD8 (Day -2) with/without anti-NK1.1 (Day -3).
      Selected groups of mice were also treated with cyclophosphamid (175 mg/kg) on Day
      2. The presence of mixed chimerism was assessed in peripheral blood, bone marrow,
      and spleen, as well as in various subpopulations of leukocytes (CD4(+), CD8(+),
      CD45/B220(+), Gr-1(+), lin(-)/Sca-1(+)/c-kit(-), lin(-)/Sca-1(+)/c-kit(+), lin(
      )/Sca-1(-)/c-kit(+)). Furthermore, the percentage of stem/progenitor cells (lin(
      )/Sca-1(+)/c-kit(-), lin(-)/Sca-1(+)/c-kit(+), lin(-)/Sca-1(-)/c-kit(+), VSEL,
      HSC) was analysed for the first time in bone marrow and peripheral blood of
      chimeric mice. The range of mixed chimerism differed significantly among various
      cell populations: it was lowest in CD8-positive cells and lin(-)/Sca-1(+)/c-kit(
      ) cells, and highest in granulocytes. The induction of mixed chimerism revealed a
      significant impact on the stem/progenitor cell frequency in recipient mice,
      providing potential therapeutic insights into the long-term immunologic tolerance
      observed in chimeric mice. Collectively, these findings contribute to further
      optimization of mixed chimerism induction protocols and might help in the
      introduction of this phenomenon into clinical practice.

PMID- 21963592
TI  - Proteomic analysis of zebrafish brain tissue following exposure to the pesticide
      prochloraz.
AB  - The hypothalamus-pituitary-gonadal (HPG) axis plays a central role in the
      maintenance of homeostasis and disruptions in its function can have important
      implications for reproduction and other critical biological processes. A number
      of compounds found in aquatic environments are known to affect the HPG axis. In
      the present study, we used two-dimensional electrophoresis to investigate the
      proteome of female and male zebrafish brain after 96 h exposure to the fungicide
      prochloraz. Prochloraz has known effects on a number of key HPG molecules,
      including antagonism of Cyp17 and Cyp19 (aromatase). Twenty-eight proteins were
      shown to be differentially expressed in the brains of females and 22 in males.
      Proteins were identified using LC-MS/MS and identities were examined relative to
      brain function in the context of changing steroid hormone levels. There was
      little overlap between sexes in proteins exhibiting differential expression.
      Proteins with known roles in metabolism, learning, neuroprotection, and calcium
      regulation were determined to be differentially regulated. Relationships between
      identified proteins were also examined using Ingenuity Pathway Analysis, and
      females were shown to exhibit enrichment of several metabolic pathways. We used
      differentially expressed proteins to establish a putative classifier consisting
      of three proteins that was able to discriminate prochloraz-exposed from control
      females. Putatively impacted brain functions and specific protein changes that
      were observed have the potential to be generalized to other that similarly impact
      steroid hormone levels.

PMID- 21963593
TI  - Transcriptional responses in Japanese medaka (Oryzias latipes) exposed to binary
      mixtures of an estrogen and anti-estrogens.
AB  - Determining ecotoxicological risks of exposure to mixtures of endocrine
      disrupting chemicals (EDCs) remains a daunting challenge in environmental
      toxicology. Recently, some studies have illustrated that transcriptional
      profiling of genes offers the potential to identify the chemical causation of
      effects that are induced by exposure to complex mixtures. In the present study,
      the transcriptional responses of a set of genes involved in the hypothalamic
      pituitary-gonadal (HPG, or HPG[L]-liver) axis of Japanese medaka (Oryzias
      latipes) were systematically examined after treatment with a combination of an
      estrogen (17alpha-ethinylestradiol [EE2], 20 ng/L) and two model anti-estrogens,
      the aromatase inhibitor (AI) letrozole (LET) and the selective estrogen-receptor
      modulator (SERM) tamoxifen (TAM), at three concentrations (30, 100 and 300 MUg/L)
      for 72 h. The data presented demonstrate that although gene transcription
      analyses increase our mechanistic understanding of the modes of action (MOAs) of
      EDCs, the characteristic of most genes altered by a certain single chemical
      exposure may not be useful for diagnostic chemical causation in a mixture
      exposure situation. For example, the induction of one vitellogenin gene (VTG1)
      transcription caused by EE2 in male fish was effectively blocked after exposure
      to a combination of EE2 and LET but not EE2 and TAM. Moreover, the responses in
      gene transcription to coexposure were elicited partially in a nonmonotonic
      concentration-dependent manner. Therefore, the application of transcriptional
      profiling of genes for screening complex environmental samples should be further
      evaluated until biomarker gene responses are robust and sensitive enough to
      properly assess the complex interactions.

PMID- 21963594
TI  - Dissolved humic substances initiate DNA-methylation in cladocerans.
AB  - DNA-methylation is one pathway of epigenetic programming of gene expression and
      can be responsive to environmental challenges such as methylating agents in the
      food. Here we report on the DNA-methylation in the cladocerans Daphnia magna and
      Moina macrocopa exposed to humic substances, ubiquitous biogeochemicals. The
      methylation of DNA can alter the stress response, presumably including exposure
      to synthetic xenobiotic chemicals.

PMID- 21963595
TI  - Attenuation of the cortisol response to stress in female rainbow trout
      chronically exposed to dietary selenomethionine.
AB  - Selenomethionine (Se-Met) is the major dietary form of selenium (Se). While Se is
      a required nutrient, it can also influence the physiological stress response
      because it stimulates greater concentrations of cortisol in blood plasma of
      exposed fish. However, little is known about the effects of exposure to Se on the
      ability to cope with a secondary stressor. In the current study, female rainbow
      trout were exposed to an environmentally relevant dietary concentration (8.47 mg
      Se/kg dry mass (dm)) of Se-Met for 126 d, after which time fish were subjected to
      a 3-min handling stressor and sampled at 2h and 24h post-stressor exposure.
      Concentrations of cortisol, cortisone, glucose, and lactate in blood plasma and
      concentrations of glycogen and triglycerides in liver and muscle were determined.
      Abundances of transcripts of proteins involved in corticosteroidogenesis were
      determined using quantitative RT-PCR. Concentrations of cortisol were
      significantly greater in blood plasma of trout exposed to Se-Met, relative to
      control trout sampled prior to the handling stressor. A typical response of
      cortisol to the handling stressor was observed in the control trout. However,
      trout exposed to Se-Met were unable to mount a cortisol response to the handling
      stressor. Concentrations of cortisone, the inactive metabolite of cortisol, were
      significantly greater following the handling stressor in trout exposed to Se-Met.
      In trout exposed to Se-Met, transcript abundance of melanocortin 2 receptor
      (mc2r) and peripheral benzodiazepine receptor (pbr) were greater, which is
      consistent with the conclusion that synthesis of cortisol was greater. However,
      abundances of transcripts of cytochrome P450 side-chain cleavage (p450scc) and
      cytochrome P450 11B1 (cyp11b1) were not significantly different between controls
      and Se-Met exposed trout. Exposure to Se-Met affected accumulation and tissue
      partitioning of glycogen and triglycerides in liver and muscle as concentrations
      of these energy reserves were greater in muscle, but not liver. Concentrations of
      glycogen and triglycerides in muscle, but not in liver, were lesser following the
      handling stressor suggesting that the muscle energy reserves are an important
      source of energy required for recovery from the handling stressor. The results of
      the study demonstrate that chronic exposure to dietary Se-Met elicits a stress
      response, but prevents a cortisol response to a secondary handling stressor, most
      likely due to cortisol inactivation. Moreover, exposure to Se-Met has effects on
      concentrations of energy reserves that are important for providing the energy
      necessary to cope with a secondary stressor.

PMID- 21963596
TI  - Biochemical biomarkers and hydrocarbons concentrations in the mangrove oyster
      Crassostrea brasiliana following exposure to diesel fuel water-accommodated
      fraction.
AB  - Understanding the toxic mechanisms by which organisms cope to environmental
      stressful conditions is a fundamental question for ecotoxicology. In this study,
      we evaluated biochemical responses and hydrocarbons bioaccumulation of the
      mangrove oyster Crassostrea brasiliana exposed for 96 h to four sublethal
      concentrations of diesel fuel water-accommodated fraction (WAF). For that
      purpose, enzymatic activities (SOD, CAT, GPx, GR, G6PDH, GST and GGT), HSP60 and
      HSP90 immunocontent and lipid peroxidation (LPO) levels were determined in the
      gill and digestive gland of oysters and related to the hydrocarbons accumulated
      in the whole soft tissues. The results of this study revealed clear biochemical
      responses to diesel fuel WAF exposure in both tissues of the oyster. The capacity
      of C. brasiliana to bioaccumulate aliphatic and aromatic hydrocarbons in a dose
      dependent manner is a strong indication of its suitability as a model in
      biomonitoring programs along the Brazilian coast, which was also validated by the
      response of the antioxidant defenses, phase II biotransformation and chaperones.
      HSP60 levels and GGT activity were the most promising biomarkers in the gill,
      while GST and GR activities stood out as suitable biomarkers for the detection of
      diesel toxicity in the digestive gland. The decrease of SOD activity and HSP90
      levels may also reflect a negative effect of diesel exposure regardless the
      tissue. The present results provide a sound preliminary report on the biochemical
      responses of C. brasiliana challenged with a petroleum by-product and should be
      carefully considered for use in the monitoring of oil and gas activities in
      Brazil.

PMID- 21963597
TI  - CREB-binding protein transcription activation domain for enhanced transgene
      expression by a positive feedback system.
AB  - The positive feedback system using a fusion protein of the sequence-specific DNA
      binding domain of yeast GAL4 and the transcription activation domain of herpes
      simplex virus VP16 (GAL4-VP16), in which GAL4-VP16 promotes its own expression as
      well as that of a reporter gene product, is useful for efficient transgene
      expression from plasmid DNA. In this study, the transcription activation domains
      of endogenous proteins, instead of VP16, were fused to the GAL4 DNA binding
      domain, and the positive feedback systems employing the novel fusion proteins
      were examined. Plasmid DNAs encoding the transcription factors were introduced
      into mouse Hepa 1-6 cells by electroporation and lipofection. Among CREB-binding
      protein (226-460), sterol regulatory element-binding protein-1 (1-140), p53 (1
      70), and Med15 (9-73), the CREB-binding protein functioned efficiently as an
      activator. These results indicated that the GAL4-CREB-binding protein is useful
      for enhanced transgene expression by the positive feedback system.

PMID- 21963598
TI  - A new method for random mutagenesis by error-prone polymerase chain reaction
      using heavy water.
AB  - Error-prone polymerase chain reactions (epPCRs) are often used to introduce
      mutations in random mutagenesis, which has been used as a tool in protein
      engineering. Here, we developed a new method of epPCR using heavy water as a
      solvent instead of normal water (H(2)O). Rhodopsin cDNA of the Ayu fish
      (Plecoglossus altivelis) was used as a template and was amplified using five
      different conditions: (A) 100% H(2)O with no Mn(2+), (B) 100% H(2)O/0.6mM Mn(2+),
      (C) 99% D(2)O with no Mn(2+), (D) 99% D(2)O/0.6mM Mn(2+) and (E) 99% H(2)(18)O
      with no Mn(2+). The 13,960 (for each of the conditions A to D) and 33,504 (for
      condition E) base pairs were sequenced. A maximum error rate of 1.8*10(
      3)errors/bp was detected in condition D, without any particular hot-spot
      mutations. A high preference for AT->GC transitions was observed in condition D,
      whereas a high preference for transitions over transversions was observed in
      condition C. All of the mutations observed in condition E were transversions.
      When conditions A and C were applied to another template, the honeybee actin
      gene, the results were comparable to those for Ayu rhodopsin. Based on these
      results, the use of heavy water, instead of H(2)O, as a solvent for epPCR can
      introduce random mutations without positional bias, template dependency or
      decreased yield. Our new epPCR method, and possibly combining the use of D(2)O
      and H(2)(18)O, may be a powerful random mutagenesis technique.

PMID- 21963599
TI  - Expression analysis of osteopontin mRNA splice variants in prostate cancer and
      benign prostatic hyperplasia.
AB  - Osteopontin splicing isoforms (OPN-SI) present differential expression patterns
      and specific tumor roles. Our aims were to characterize OPN-SI expression in
      prostate cancer (PCa) and benign prostate hyperplasia (BPH) tissues, besides
      evaluating their potential as biomarkers for PCa diagnosis and prognostic
      implications. Prostatic tissue specimens were obtained from 40 PCa and 30 benign
      prostate hyperplasia (BPH) patients. Quantitative real time PCR (qRT-PCR) was
      used to measure OPN-SI mRNA expression. Immunohistochemical analysis was
      performed using an anti-OPNc polyclonal antibody. Biostatistical analyses
      evaluated the association of OPN-SI and total Prostate Specific Antigen (PSA)
      serum levels with clinical and pathological data. PCa tissue samples presented
      significantly higher levels of OPNa, OPNb and OPNc transcripts (p<0.01) than in
      BPH specimens. OPN-SI mRNA expression were positively correlated with Gleason
      Score (p<0.01). ROC curves and logistic regression analyses demonstrated that OPN
      SI and PSA were able to distinguish PCa from BPH patients (p<0.01). The OPNc
      isoform was the most upregulated variant and the best marker to distinguish
      patients' groups, presenting sensitivity and specificity of 90% and 100%,
      respectively. Immunohistochemistry analysis also demonstrated OPNc upregulation
      in PCa samples as compared to BPH tissues. OPNcprotein was also strongly stained
      PCa tissues presenting High Gleason Score. Multivariate analysis indicated that
      OPNc expression levels above the cut-off value presented a chance 4-fold higher
      for PCa occurrence. We conclude that OPN-SI were overexpressed in PCa tissues,
      strongly associated with PCa occurrence and with tumor cell differentiation. Our
      results suggest OPNc splicing isoform as an important biomarker contributing to
      improve PCa diagnosis and prognosis, besides providing insights into early steps
      of PCa carcinogenesis.

PMID- 21963600
TI  - Nucleic acid quantity and quality from paraffin blocks: defining optimal
      fixation, processing and DNA/RNA extraction techniques.
AB  - Although the extraction and analysis of nucleic acids from formalin-fixed
      paraffin-embedded tissues is a routine and growing part of pathology practice, no
      generally accepted recommendations exist to guide laboratories in their selection
      of tissue fixation, processing and DNA/RNA extraction techniques. The aim of this
      study was to determine how fixation method and length, paraffin embedding,
      processing conditions and nucleic acid extraction methods affect quality and
      quantity of DNA and RNA, and their performance in downstream applications. Nine
      tissue samples were subjected to freezing, fixation in formalin for <24 h and 7
      days followed by conventional processing, and fixation in molecular fixative for
      <24 h and 7 days followed by rapid processing. DNA and RNA were isolated using in
      house extraction and commercial kits, and assessed by PCR reactions for amplicons
      with varying sizes ranging from 268 to 1327 bp and one-step RT-PCR for 621 bp and
      816 bp amplicons of housekeeping genes. Molecular fixative (MF) appeared to
      perform well under nearly all circumstances (extraction methods, fixation lengths
      and longer amplicons), often performing as well as frozen samples. Formalin
      fixation generally performed well only for shorter length amplicons and short
      fixation (<24 h). WaxFree kit showed consistently higher success rates for DNA
      and poorer rates for RNA. RecoverAll kit generally performed suboptimally in
      combination with prolonged formalin fixation. In conclusion, the Molecular
      Fixative regardless of fixation length, and the rapid tissue processing system
      were able to preserve large DNA and RNA fragments in paraffin blocks, making
      these techniques preferable for use in downstream molecular diagnostic assays.

PMID- 21963601
TI  - The ribosome-related protein, SBDS, is critical for normal erythropoiesis.
AB  - Although anemia is common in Shwachman- Diamond syndrome (SDS), the underlying
      mechanism remains unclear. We asked whether SBDS, which is mutated in most SDS
      patients, is critical for erythroid development. We found that SBDS expression is
      high early during erythroid differentiation. Inhibition of SBDS in CD34(+)
      hematopoietic stem cells and early progenitors (HSC/Ps) and K562 cells led to
      slow cell expansion during erythroid differentiation. Induction of erythroid
      differentiation resulted in markedly accelerated apoptosis in the knockdown
      cells; however, proliferation was only mildly reduced. The percentage of cells
      entering differentiation was not reduced. Differentiation also increased the
      oxidative stress in SBDS-knockdown K562 cells, and antioxidants enhanced the
      expansion capability of differentiating SBDS-knockdown K562 cells and colony
      production of SDS patient HSC/Ps. Erythroid differentiation also resulted in
      reduction of all ribosomal subunits and global translation. Furthermore,
      stimulation of global translation with leucine improved the erythroid cell
      expansion of SBDS-knockdown cells and colony production of SDS patient HSC/Ps.
      Leucine did not reduce the oxidative stress in SBDS-deficient K562 cells. These
      results demonstrate that SBDS is critical for normal erythropoiesis.
      Erythropoietic failure caused by SBDS deficiency is at least in part related to
      elevated ROS levels and translation insufficiency because antioxidants and
      leucine improved cell expansion.

PMID- 21963602
TI  - Mechanisms of antigen presentation to T cells in murine graft-versus-host
      disease: cross-presentation and the appearance of cross-presentation.
AB  - Recipient antigen-presenting cells (APCs) initiate GVHD by directly presenting
      host minor histocompatibility antigens (miHAs) to donor CD8 cells. However, later
      after transplantation, host APCs are replaced by donor APCs, and if pathogenic
      CD8 cells continue to require APC stimulation, then donor APCs must cross-present
      host miHAs. Consistent with this, CD8-mediated GVHD is reduced when donor APCs
      are MHC class I(-). To study cross-presentation, we used hosts that express
      defined MHC class I K(b)-restricted miHAs, crossed to K(b)-deficient backgrounds,
      such that these antigens cannot be directly presented. Cross-priming was
      surprisingly efficient, whether antigen was restricted to the hematopoietic or
      nonhematopoietic compartments. Cross-primed CD8 cells were cytolytic and produced
      IFN-gamma. CD8 cells were exclusively primed by donor CD11c(+) cells, and optimal
      cross-priming required that they are stimulated by both type I IFNs and CD40L. In
      studying which donor APCs acquire host miHAs, we made the surprising discovery
      that there was a large-scale transfer of transmembrane proteins from irradiated
      hosts, including MHC class I-peptide complexes, to donor cells, including
      dendritic cells. Donor dendritic cells that acquired host MHC class I-peptide
      complexes were potent stimulators of peptide-specific T cells. These studies
      identify new therapeutic targets for GVHD treatment and a novel mechanism whereby
      donor APCs prime host-reactive T cells.

PMID- 21963603
TI  - Frequent loss of HLA alleles associated with copy number-neutral 6pLOH in
      acquired aplastic anemia.
AB  - Idiopathic aplastic anemia (AA) is a common cause of acquired BM failure.
      Although autoimmunity to hematopoietic progenitors is thought to be responsible
      for its pathogenesis, little is known about the molecular basis of this
      autoimmunity. Here we show that a substantial proportion of AA patients harbor
      clonal hematopoiesis characterized by the presence of acquired copy number
      neutral loss of heterozygosity (CNN-LOH) of the 6p arms (6pLOH). The 6pLOH
      commonly involved the HLA locus, leading to loss of one HLA haplotype. Loss of
      HLA-A expression from multiple lineages of leukocytes was confirmed by flow
      cytometry in all 6pLOH(+) cases. Surprisingly, the missing HLA-alleles in
      6pLOH(+) clones were conspicuously biased to particular alleles, including HLA
      A*02:01, A*02:06, A*31:01, and B*40:02. A large-scale epidemiologic study on the
      HLA alleles of patients with various hematologic diseases revealed that the 4 HLA
      alleles were over-represented in the germline of AA patients. These findings
      indicate that the 6pLOH(+) hematopoiesis found in AA represents "escapes"
      hematopoiesis from the autoimmunity, which is mediated by cytotoxic T cells that
      target the relevant auto-antigens presented on hematopoietic progenitors through
      these class I HLAs. Our results provide a novel insight into the genetic basis of
      the pathogenesis of AA.

PMID- 21963604
TI  - Sic1 plays a role in timing and oscillatory behaviour of B-type cyclins.
AB  - Budding yeast cell cycle oscillates between states of low and high cyclin
      dependent kinase activity, driven by association of Cdk1 with B-type (Clb)
      cyclins. Various Cdk1-Clb complexes are activated and inactivated in a fixed,
      temporally regulated sequence, inducing the behaviour known as "waves of
      cyclins". The transition from low to high Clb activity is triggered by
      degradation of Sic1, the inhibitor of Cdk1-Clb complexes, at the entry to S
      phase. The G(1) phase is characterized by low Clb activity and high Sic1 levels.
      High Clb activity and Sic1 proteolysis are found from the beginning of the S
      phase until the end of mitosis. The mechanism regulating the appearance on
      schedule of Cdk1-Clb complexes is currently unknown. Here, we analyse
      oscillations of Clbs, focusing on the role of their inhibitor Sic1. We compare
      mathematical networks differing in interactions that Sic1 may establish with Cdk1
      Clb complexes. Our analysis suggests that the wave-like cyclins pattern derives
      from the binding of Sic1 to all Clb pairs rather than from Clb degradation. These
      predictions are experimentally validated, showing that Sic1 indeed interacts and
      coexists in time with Clbs. Intriguingly, a sic1Delta strain looses cell cycle
      regulated periodicity of Clbs, which is observed in the wild type, whether a SIC1
      0P strain delays the formation of Clb waves. Our results highlight an additional
      role for Sic1 in regulating Cdk1-Clb complexes, coordinating their appearance.

PMID- 21963605
TI  - Potential applications of enzymes immobilized on/in nano materials: A review.
AB  - Several new types of carriers and technologies have been implemented in the
      recent past to improve traditional enzyme immobilization which aimed to enhance
      enzyme loading, activity and stability to decrease the enzyme biocatalyst cost in
      industrial biotechnology. These include cross-linked enzyme aggregates, microwave
      assisted immobilization, click chemistry technology, mesoporous supports and most
      recently nanoparticle-based immobilization of enzymes. The union of the specific
      physical, chemical, optical and electrical properties of nanoparticles with the
      specific recognition or catalytic properties of biomolecules has led to their
      appearance in myriad novel biotechnological applications. They have been applied
      time and again for immobilization of industrially important enzymes with improved
      characteristics. The high surface-to-volume ratio offered by nanoparticles
      resulted in the concentration of the immobilized entity being considerably higher
      than that afforded by experimental protocols based on immobilization on planar 2
      D surfaces. Enzymes immobilized on nanoparticles showed a broader working pH and
      temperature range and higher thermal stability than the native enzymes. Compared
      with the conventional immobilization methods, nanoparticle based immobilization
      served three important features; (i) nano-enzyme particles are easy to synthesize
      in high solid content without using surfactants and toxic reagents, (ii)
      homogeneous and well defined core-shell nanoparticles with a thick enzyme shell
      can be obtained, and (iii) particle size can be conveniently tailored within
      utility limits. In addition, with the growing attention paid to cascade enzymatic
      reaction and in vitro synthetic biology, it is possible that co-immobilization of
      multi-enzymes could be achieved on these nanoparticles.

PMID- 21963606
TI  - [Consensus document by the Spanish Society of Paediatric Infectious Diseases and
      the advisory committee on vaccines of the Spanish Paediatrics Association on
      vaccination in immunocompromised children].
AB  - Vaccination in immunocompromised infants, children and adolescents is a major
      aspect in the follow-up of this complex pathology in specific Paediatric Units.
      Vaccination is also an important prevention tool, as this can, to a certain
      extent, determine the morbidity and mortality in these patients. This consensus
      document was jointly prepared by Working Groups of the Spanish Society of
      Paediatric Infectious Diseases and the Advisory Committee on Vaccines of the
      Spanish Paediatric Association, who are usually involved in updating the
      management of vaccinations in immunocompromised children, and reflects their
      opinions. The consensus specifically summarises indications for vaccination in
      the following special paediatric populations: Solid organ and haematopoietic
      transplant-recipients; primary immunodeficiency; asplenic children; non
      previously transplanted immunocompromised patients; chronically ill patients; HIV
      infected children and also the vaccines recommended for immunodeficient children
      who travel.

PMID- 21963607
TI  - MS3 eliminates ratio distortion in isobaric multiplexed quantitative proteomics.
AB  - Quantitative mass spectrometry-based proteomics is highly versatile but not
      easily multiplexed. Isobaric labeling strategies allow mass spectrometry-based
      multiplexed proteome quantification; however, ratio distortion owing to protein
      quantification interference is a common effect. We present a two-proteome model
      (mixture of human and yeast proteins) in a sixplex isobaric labeling system to
      fully document the interference effect, and we report that applying triple-stage
      mass spectrometry (MS3) almost completely eliminates interference.

PMID- 21963608
TI  - Gas-phase purification enables accurate, multiplexed proteome quantification with
      isobaric tagging.
AB  - We describe a mass spectrometry method, QuantMode, which improves accuracy of
      isobaric tag-based quantification by alleviating the pervasive problem of
      precursor interference, simultaneous isolation and fragmentation of impurities,
      through gas-phase purification. QuantMode analysis of a yeast sample
      'contaminated' with interfering human peptides showed substantially improved
      quantitative accuracy compared to a standard scan, with a small loss of spectral
      identifications. This technique enables large-scale, multiplexed quantitative
      proteomics using isobaric tagging.

PMID- 21963609
TI  - Cardiovascular reactivity and proactive and reactive relational aggression among
      women with and without a history of sexual abuse.
AB  - This study examined the association between cardiovascular reactivity and
      proactive and reactive functions of relational aggression among women with and
      without a history of sexual abuse. Heart rate reactivity, blood pressure
      reactivity, and respiratory sinus arrhythmia reactivity while recounting a
      relational stressor (e.g., being left out) were assessed. Participants provided
      self-reports of relational aggression and a history of sexual abuse prior to age
      16. Results indicated that cardiovascular reactivity was only associated with
      relational aggression among women with a history of sexual abuse. In addition,
      whereas blunted reactivity was associated with proactive relational aggression,
      exaggerated reactivity was associated with reactive relational aggression. These
      findings highlight the importance of considering contextual moderators of the
      association between cardiovascular reactivity and aggression; moreover, results
      highlight distinct cardiovascular correlates of different functions of
      aggression. Finally, the findings underscore the need for additional research
      examining the physiological correlates of aggressive behavior among women.

PMID- 21963610
TI  - BEAGLE: an application programming interface and high-performance computing
      library for statistical phylogenetics.
AB  - Phylogenetic inference is fundamental to our understanding of most aspects of the
      origin and evolution of life, and in recent years, there has been a concentration
      of interest in statistical approaches such as Bayesian inference and maximum
      likelihood estimation. Yet, for large data sets and realistic or interesting
      models of evolution, these approaches remain computationally demanding. High
      throughput sequencing can yield data for thousands of taxa, but scaling to such
      problems using serial computing often necessitates the use of nonstatistical or
      approximate approaches. The recent emergence of graphics processing units (GPUs)
      provides an opportunity to leverage their excellent floating-point computational
      performance to accelerate statistical phylogenetic inference. A specialized
      library for phylogenetic calculation would allow existing software packages to
      make more effective use of available computer hardware, including GPUs. Adoption
      of a common library would also make it easier for other emerging computing
      architectures, such as field programmable gate arrays, to be used in the future.
      We present BEAGLE, an application programming interface (API) and library for
      high-performance statistical phylogenetic inference. The API provides a uniform
      interface for performing phylogenetic likelihood calculations on a variety of
      compute hardware platforms. The library includes a set of efficient
      implementations and can currently exploit hardware including GPUs using NVIDIA
      CUDA, central processing units (CPUs) with Streaming SIMD Extensions and related
      processor supplementary instruction sets, and multicore CPUs via OpenMP. To
      demonstrate the advantages of a common API, we have incorporated the library into
      several popular phylogenetic software packages. The BEAGLE library is free open
      source software licensed under the Lesser GPL and available from http://beagle
      lib.googlecode.com. An example client program is available as public domain
      software.

PMID- 21963611
TI  - Admission levels of soluble CD137 are increased in patients with acute
      pancreatitis and are associated with subsequent complications.
AB  - The progression of acute pancreatitis to necrotizing pancreatitis which often
      results in high morbidity and mortality is difficult to predict. Here we report
      that serum concentrations of sCD137 are increased in patients with acute
      pancreatitis. Admission levels and 10-day median sCD137 levels positively
      correlate with markers of biliary pancreatitis and the 10-day sCD137 median is
      significantly higher in metabolic than in alcoholic pancreatitis. Serum
      concentrations of sCD137 at time of admission and the 10-day median of sCD137
      correlate with the Ranson and APACHE II disease scores but not with the
      radiological Balthazar and Schroeder scores that reflect pancreatic and
      peripancreatic necrosis. Further, sCD137 levels correlate with the probability of
      complications and lethality. The association of sCD137, a product of activated T
      cells, with the severity of acute pancreatitis suggests that T cells contribute
      to the pathogenesis of acute pancreatitis.

PMID- 21963612
TI  - Glutaredoxin GRXS13 plays a key role in protection against photooxidative stress
      in Arabidopsis.
AB  - Glutaredoxins (GRXs) belong to the antioxidant and signalling network involved in
      the cellular response to oxidative stress in bacterial and eukaryotic cells. In
      spite of the high number of GRX genes in plant genomes, the biological functions
      and physiological roles of most of them remain unknown. Here the functional
      characterization of the Arabidopsis GRXS13 gene (At1g03850), that codes for two
      CC-type GRX isoforms, is reported. The transcript variant coding for the GRXS13.2
      isoform is predominantly expressed under basal conditions and is the isoform that
      is induced by photooxidative stress. Transgenic lines where the GRXS13 gene has
      been knocked down show increased basal levels of superoxide radicals and reduced
      plant growth. These lines also display reduced tolerance to methyl viologen (MeV)
      and high light (HL) treatments, both conditions of photooxidative stress
      characterized by increased production of superoxide ions. Consistently, lines
      overexpressing the GRXS13.2 variant show reduced MeV- and HL-induced damage.
      Alterations in GRXS13 expression also affect superoxide levels and the
      ascorbate/dehydroascorbate ratio after HL-induced stress. These results indicate
      that GRXS13 gene expression is critical for limiting basal and photooxidative
      stress-induced reactive oxygen species (ROS) production. Together, these results
      place GRXS13.2 as a member of the ROS-scavenging/antioxidant network that shows a
      particularly low functional redundancy in the Arabidopsis GRX family.

PMID- 21963613
TI  - Genetic control of biennial bearing in apple.
AB  - Although flowering in mature fruit trees is recurrent, floral induction can be
      strongly inhibited by concurrent fruiting, leading to a pattern of irregular
      fruiting across consecutive years referred to as biennial bearing. The genetic
      determinants of biennial bearing in apple were investigated using the 114
      flowering individuals from an F(1) population of 122 genotypes, from a
      'Starkrimson' (strong biennial bearer)*'Granny Smith' (regular bearer) cross. The
      number of inflorescences, and the number and the mass of harvested fruit were
      recorded over 6 years and used to calculate 26 variables and indices quantifying
      yield, precocity of production, and biennial bearing. Inflorescence traits
      exhibited the highest genotypic effect, and three quantitative trait loci (QTLs)
      on linkage group (LG) 4, LG8, and LG10 explained 50% of the phenotypic
      variability for biennial bearing. Apple orthologues of flowering and hormone
      related genes were retrieved from the whole-genome assembly of 'Golden Delicious'
      and their position was compared with QTLs. Four main genomic regions that contain
      floral integrator genes, meristem identity genes, and gibberellin oxidase genes
      co-located with QTLs. The results indicated that flowering genes are less likely
      to be responsible for biennial bearing than hormone-related genes. New hypotheses
      for the control of biennial bearing emerged from QTL and candidate gene co
      locations and suggest the involvement of different physiological processes such
      as the regulation of flowering genes by hormones. The correlation between tree
      architecture and biennial bearing is also discussed.

PMID- 21963614
TI  - Improving crop productivity and resource use efficiency to ensure food security
      and environmental quality in China.
AB  - In recent years, agricultural growth in China has accelerated remarkably, but
      most of this growth has been driven by increased yield per unit area rather than
      by expansion of the cultivated area. Looking towards 2030, to meet the demand for
      grain and to feed a growing population on the available arable land, it is
      suggested that annual crop production should be increased to around 580 Mt and
      that yield should increase by at least 2% annually. Crop production will become
      more difficult with climate change, resource scarcity (e.g. land, water, energy,
      and nutrients) and environmental degradation (e.g. declining soil quality,
      increased greenhouse gas emissions, and surface water eutrophication). To pursue
      the fastest and most practical route to improved yield, the near-term strategy is
      application and extension of existing agricultural technologies. This would lead
      to substantial improvement in crop and soil management practices, which are
      currently suboptimal. Two pivotal components are required if we are to follow new
      trajectories. First, the disciplines of soil management and agronomy need to be
      given increased emphasis in research and teaching, as part of a grand food
      security challenge. Second, continued genetic improvement in crop varieties will
      be vital. However, our view is that the biggest gains from improved technology
      will come most immediately from combinations of improved crops and improved
      agronomical practices. The objectives of this paper are to summarize the
      historical trend of crop production in China and to examine the main constraints
      to the further increase of crop productivity. The paper provides a perspective on
      the challenge faced by science and technology in agriculture which must be met
      both in terms of increased crop productivity but also in increased resource use
      efficiency and the protection of environmental quality.

PMID- 21963615
TI  - Any trait or trait-related allele can confer drought tolerance: just design the
      right drought scenario.
AB  - Most traits associated with drought tolerance have a dual effect, positive in
      very severe scenarios and negative in milder scenarios, or the opposite trend.
      Their effects also depend on other climatic conditions such as evaporative demand
      or light, and on management practices. This is the case for processes associated
      with cell protection and with avoidance, but also for the maintenance of growth
      or photosynthesis, high water use efficiency, large root systems or reduced
      abortion rate under water deficit. Therefore, spectacular results obtained in one
      drought scenario may have a limited interest for improving food security in other
      geographical areas with water scarcity. The most relevant questions on drought
      tolerance are probably, 'Does a given allele confer a positive effect on yield in
      an appreciable proportion of years/scenarios in a given area or target population
      of environment (TPE)?'; 'In a given site or TPE, what is the trade-off between
      risk avoidance and maintained performance?'; and 'Will a given allele or trait
      have an increasingly positive effect with climate change?' Considerable progress
      has already occurred in drought tolerance. Nevertheless, explicitly associating
      traits for tolerance to drought scenarios may have profound consequences on the
      genetic strategies, with a necessary involvement of modelling.

PMID- 21963616
TI  - Hypothesis driven drug design: improving quality and effectiveness of the design
      make-test-analyse cycle.
AB  - In drug discovery, the central process of constructing and testing hypotheses,
      carefully conducting experiments and analysing the associated data for new
      findings and information is known as the design-make-test-analyse cycle. Each
      step relies heavily on the inputs and outputs of the other three components. In
      this article we report our efforts to improve and integrate all parts to enable
      smooth and rapid flow of high quality ideas. Key improvements include enhancing
      multi-disciplinary input into 'Design', increasing the use of knowledge and
      reducing cycle times in 'Make', providing parallel sets of relevant data within
      ten working days in 'Test' and maximising the learning in 'Analyse'.

PMID- 21963617
TI  - The comparison of radiation dose between C-arm flat-detector CT (DynaCT) and
      multi-slice CT (MSCT): a phantom study.
AB  - PURPOSE: To assess and compare the radiation dose of DynaCT in phantoms to that
      of MSCT. METHODS AND MATERIALS: A male Anderson Radiation Therapy 200 phantom
      with embedded thermoluminescence dosimeters (TLDs) was scanned with DynaCT (Axiom
      Artis dTA, Siemens Healthcare, Forchheim, Germany) and MSCTs (MSCT1: Lightspeed
      VCT, GE, Milwaukee, USA; MSCT2: Sensation Cardiac 64, Siemens Healthcare,
      Erlangen, Germany), respectively. For DynaCT, radiation exposure data with
      automatic exposure control were obtained from scanning of head, chest and
      abdomen. For MSCT, scanning protocols for head, chest, and abdomen were examined
      under conventional exposure conditions. Effective doses were calculated from LiF
      TLD measurements according to ICRP103. A Catphan phantom (Phantom Lab, USA) was
      used to evaluate the spatial resolution and low contrast detectability of DynaCT
      and MSCT. RESULTS: The effective doses for DynaCT from head, chest and abdomen
      scanning were 1.18, 7.32, 7.48 mSv (20 s scan) and 0.85, 6.01, 7.04 mSv (8 s
      scan); the effective doses for MSCT from head, chest and abdomen scanning were
      3.33, 7.62 and 8.42 mSv (MSCT1), and 1.89, 7.52, 8.23 mSv (MSCT2). Significant
      difference between the organ doses from DynaCT and from MSCT (p<.05) was shown.
      The spatial resolution of 12 lp/cm was achieved and it was able to recognize a
      3mm low contrast object at 0.5% contrast level in DynaCT, which was on the same
      level as in the MSCT images. CONCLUSION: The phantom study indicates that DynaCT
      applies significantly less dose to patient and achieves similar spatial
      resolution and low contrast detectability to standard diagnostic MSCT.

PMID- 21963618
TI  - Upfront allogeneic blood stem cell transplantation for patients with high-risk
      myelodysplastic syndrome or secondary acute myeloid leukemia using a FLAMSA-based
      high-dose sequential conditioning regimen.
AB  - Patients suffering from high-risk myelodysplastic syndrome (MDS) or acute
      myelogenous leukemia (AML) secondary to MDS (sAML) are characterized by poor
      response to conventional cytotoxic chemotherapy. The purpose of our prospective
      single-center study was to examine the safety and efficacy of an allogeneic
      hematopoietic stem cell transplantation (HSCT) following a sequential
      conditioning regimen as first-line therapy for previously untreated patients with
      high-risk MDS or sAML. Between November 2003 and June 2010, 30 patients (20 high
      risk MDS, 10 sAML) received fludarabine (4 * 30 mg/m(2)), amsacrine (4 * 100
      mg/m(2)), and Ara-C (4 * 2 g/m(2), FLAMSA). After 2 to 3 days of rest, patients
      received high-dose melphalan alone (200 mg/m(2) for patients with an age <50
      years, 150 mg/m(2) for patients with an age between 50 and 60 years, and 100
      mg/m(2) for patients with an age >60 years; n = 24) or melphalan and thiotepa (10
      mg/kg, Mel/Thio, n = 6). Following these high-dose conditioning regimens, a
      median number of 7.7 * 10(6) CD34(+) cells/kg body weight (range: 2.9 * 10(6)
      17.2 * 10(6)) were transplanted from 13 related or 17 unrelated donors.
      Antithymocyte globulin (Fresenius 30-60 mg/kg) as well as tacrolimus and
      mycophenolate mofetil were used for graft-versus-host disease (GVHD) prophylaxis.
      All patients except 1 with primary graft failure achieved complete remission
      after HSCT. After a median follow-up time of 28 months (range: 7-81), 21 patients
      (70%) were alive and free of disease. Overall, 4 patients relapsed. At 2 years,
      overall survival, event-free survival, and treatment-related mortality were 70%,
      63%, and 30%, respectively. Because of undue toxicity, thiotepa is no longer part
      of the conditioning regimen. Our results add to the body of evidence that a
      FLAMSA-based sequential conditioning therapy is effective for previously
      untreated patients with high-risk MDS or sAML.

PMID- 21963619
TI  - Prophylactic effects of interleukin-2 receptor antagonists against graft-versus
      host disease following unrelated donor peripheral blood stem cell
      transplantation.
AB  - Basiliximab and daclizumab, two interleukin-2 receptor antagonists (IL-2RAs),
      prevent graft failure in renal transplantation, which also effectively treat
      steroid-refractory graft-versus-host disease (GVHD). However, only a few studies
      report that IL-2RAs prevent GVHD. Here we first retrospectively explored the
      prophylactic effects of basiliximab or daclizumab against GVHD in 82 patients
      with hematologic malignancies following unrelated donor-peripheral blood stem
      cell transplantation (URD-PBSCT). All recipients achieved engraftment. The rates
      of grade II-IV and III-IV acute GVHD (aGVHD) were 35.4% and 15.9%, respectively.
      Chronic GVHD (cGVHD) developed in 38.7% of evaluable patients. The
      transplantation-related mortality was 13.4%, while relapse rate was 8.5%. The 2
      year overall survival (OS) reached 77.1% and disease-free survival (DFS)
      accumulated to 72.2%. The side effects of basiliximab and daclizumab were
      moderate and tolerable. There were no significant differences in aGVHD onset and
      survival between the daclizumab and basiliximab groups. However, basiliximab
      presented superior prophylactic effects on cGVHD than daclizumab. In conclusion,
      basiliximab or daclizumab prevents GVHD efficiently and feasibly following URD
      PBSCT, and contributes to favorable outcome. Basiliximab has a similar effect on
      aGVHD but superior activity against cGVHD. Further prospective and randomized
      control studies are needed.

PMID- 21963620
TI  - The role of cytotoxic therapy with hematopoietic stem cell transplantation in the
      treatment of adult acute lymphoblastic leukemia: update of the 2006 evidence
      based review.

PMID- 21963622
TI  - Scoring HLA class I mismatches by HistoCheck does not predict clinical outcome in
      unrelated hematopoietic stem cell transplantation.
AB  - Currently, there is no well-accepted rating system for reliably predicting which
      HLA-mismatched (MM) unrelated donor should be selected for a patient without an
      HLA allele-matched donor. We evaluated the ability of an MM ranking system,
      HistoCheck, to predict the risk associated with HLA class I disparity in a
      population of 744 single allele or antigen HLA-A, -B, or -C MM myeloablative
      unrelated donor hematopoietic stem cell transplantation recipients with acute
      myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia,
      or myelodysplastic syndrome, facilitated through the National Marrow Donor
      Program between 1988 and 2003. Multivariate models were used to adjust for other
      significant clinical risk factors. HLA MMs were scored using the HistoCheck Web
      based tool, and the patients were divided into 4 quartiles: dissimilarity score
      (DSS) 1.04-2.84 (allele MM), DSS >2.84-13.75 (allele and antigen MM), DSS >13.75
      19.39 (antigen MM), and DSS >19.39-36.62 (antigen MM). Using the lowest scoring
      quartile as the reference, the DSS groups were evaluated for associations with
      relapse, treatment-related mortality, acute and chronic graft-versus-host
      disease, leukemia-free survival, and overall survival in the entire cohort and
      also in subset analyses by disease and disease stage. No significant associations
      were found between DSS and any outcomes in the overall cohort using the quartile
      categories or treating DSS as a continuous variable. Higher DSS scores were
      associated with decreased engraftment in early-stage disease (P = .0003), but not
      in other disease stages. In summary, DSS does not correlate with transplantation
      outcomes, and the HistoCheck scoring system does not provide an effective
      technique for ranking HLA class I MM. The dataset used in this study is available
      to evaluate new algorithms proposed for donor selection.

PMID- 21963623
TI  - Safety and efficacy of CMX001 as salvage therapy for severe adenovirus infections
      in immunocompromised patients.
AB  - No therapeutic agent has yet been established as the definitive therapy for
      adenovirus infections. We describe the clinical experience of 13
      immunocompromised patients who received CMX001 (hexadecyloxypropyl cidofovir), an
      orally bioavailable lipid conjugate of cidofovir, for adenovirus disease. We
      retrospectively analyzed 13 patients with adenovirus disease and viremia treated
      with CMX001; data were available for >= 4 weeks after initiation of CMX001
      therapy. Virologic response (VR) was defined as a 99% drop from baseline or
      undetectable adenovirus DNA in serum. The median age of the group was 6 years
      (range, 0.92-66 years). One patient had severe combined immunodeficiency, 1
      patient was a small bowel transplant recipient, and 11 were allogeneic stem cell
      transplant recipients. Adenovirus disease was diagnosed at a median of 75 days
      (range, 15-720 days) after transplantation. All patients received i.v. cidofovir
      for a median of 21 days (range, 5-90 days) before CMX001 therapy. The median
      absolute lymphocyte count at CMX001 initiation was 300 cells/MUL (range, 7-1500
      cells/MUL). Eight patients (61.5%) had a >= 1 log10 drop in viral load after the
      first week of therapy. By week 8, 9 patients (69.2%) demonstrated a VR, with a
      median time to achieve VR of 7 days (range, 3-35 days). The change in absolute
      lymphocyte count was inversely correlated with the change in log10 viral load
      only at week 6 (r = -0.74; P = .03). Patients with VR had longer survival than
      those without VR (median 196 days versus 54.5 days; P = .04). No serious adverse
      events were attributed to CMX001 during therapy. CMX001 may be a promising
      therapeutic option for the treatment of severe adenovirus disease in
      immunocompromised patients.

PMID- 21963621
TI  - Mesenchymal stromal cells: a new tool against graft-versus-host disease?
AB  - Mesenchymal stromal cells (MSCs) represent a heterogeneous subset of multipotent
      cells that can be isolated from several tissues including bone marrow and fat.
      MSCs exhibit immunomodulatory and anti-inflammatory properties that prompted
      their clinical use as prevention and/or treatment for severe graft-versus-host
      disease (GVHD). Although a number of phase I-II studies have suggested that MSC
      infusion was safe and might be effective for preventing or treating acute GVHD,
      definitive proof of their efficacy remains lacking thus far. Multicenter
      randomized studies are ongoing to more precisely assess the impact of MSC
      infusion on GVHD prevention/treatment, whereas further research is performed in
      vitro and in animal models with the aims of determining the best way to expand
      MSCs ex vivo as well as the most efficient dose and schedule of MSCs
      administration. After introducing GVHD, MSC biology, and results of MSC infusion
      in animal models of allogeneic hematopoietic cell transplantation, this article
      reviews the results of the first clinical trials investigating the use of MSC
      infusion as prevention or treatment of GVHD.

PMID- 21963625
TI  - Synthesis, photophysical and electrochemical properties of a mixed bipyridyl
      phenanthrolyl ligand Ru(II) heteroleptic complex having trans-2-methyl-2-butenoic
      acid functionalities.
AB  - In this work, two ligands: 4-(trans-2-Methyl-2-butenoic acid)-2,2'-bipyridine)
      (L(1)) and 5-(trans-2-methyl-2-butenoic acid)-1,10-phenanthroline (L(2)), with
      the corresponding mixed-ligand heteroleptic Ru(II) complex were synthesized and
      characterized by FT-IR, 1H-, 13C-NMR spectroscopy and elemental analysis. The
      influence of the mixed functionalized polypyridyl ruthenium(II) complex on the
      photophysical and electrochemical properties were investigated and compared to
      individual single-ligand homoleptic complexes. Interestingly, the mixed-ligand
      complex formulated as [RuL(1)L(2)(NCS)(2)] exhibits broad and intense metal-to
      ligand charge transfer (MLCT) absorption with a high molar extinction coefficient
      (lambda(max) = 514 nm, epsilon = 69,700 M(-1) cm(-1)), better than those of
      individual single-ligand complexes, [Ru(L(1))(2)(NCS)(2)] and
      [Ru(L(2))(2)(NCS)(2)], and a strong photoluminescence intensity ratio in the red
      region at lambda(em) = 686 nm. The electrochemical properties of the complex
      indicated that the redox processes are ligand-based.

PMID- 21963624
TI  - Down-regulation of Treg cells and up-regulation of TH1/TH2 cytokine ratio were
      induced by polysaccharide from Radix Glycyrrhizae in H22 hepatocarcinoma bearing
      mice.
AB  - Radix Glycyrrhizae polysaccharide (GP) possesses multiple pharmacological
      activities. However, the effect of GP on CD4+CD25+ regulatory T (Treg) cells has
      not been elucidated. This study aimed to investigate the effects of GP on Treg
      cells and Th1/Th2 cytokines in H22 hepatocarcinoma tumor-bearing mice. The
      results demonstrated that GP inhibits tumor progression. In the lymph nodes of
      the tumor microenvironment and spleen, the proportion of Treg cells was
      significantly higher in the tumor-bearing mice. GP administration down-regulated
      the population of Treg cells (P < 0.01) and decreased lymph node Foxp3 and IL-10
      mRNA expression (P < 0.01). In addition, GP treatment decreased IL-10 and TGF
      beta level (P < 0.01) and increased IL-2 and IL-12p70 level in serum (P < 0.01).
      In conclusion, GP reduced the proportion of Treg cells and Foxp3 lowered
      expression in Treg cells, and up-regulated Th1/Th2 cytokine ratio in serum in the
      tumor bearing mice, which might partially cause the inhibition of tumor growth.

PMID- 21963626
TI  - Microfluidic devices: useful tools for bioprocess intensification.
AB  - The dawn of the new millennium saw a trend towards the dedicated use of
      microfluidic devices for process intensification in biotechnology. As the last
      decade went by, it became evident that this pattern was not a short-lived fad,
      since the deliverables related to this field of research have been consistently
      piling-up. The application of process intensification in biotechnology is
      therefore seemingly catching up with the trend already observed in the chemical
      engineering area, where the use of microfluidic devices has already been upgraded
      to production scale. The goal of the present work is therefore to provide an
      updated overview of the developments centered on the use of microfluidic devices
      for process intensification in biotechnology. Within such scope, particular focus
      will be given to different designs, configurations and modes of operation of
      microreactors, but reference to similar features regarding microfluidic devices
      in downstream processing will not be overlooked. Engineering considerations and
      fluid dynamics issues, namely related to the characterization of flow in
      microchannels, promotion of micromixing and predictive tools, will also be
      addressed, as well as reflection on the analytics required to take full advantage
      of the possibilities provided by microfluidic devices in process intensification.
      Strategies developed to ease the implementation of experimental set-ups anchored
      in the use of microfluidic devices will be briefly tackled. Finally, realistic
      considerations on the current advantages and limitation on the use of
      microfluidic devices for process intensification, as well as prospective near
      future developments in the field, will be presented.

PMID- 21963627
TI  - Identification of gamma-AApeptides with potent and broad-spectrum antimicrobial
      activity.
AB  - We report the identification of a new class of antimicrobial peptidomimetics
      gamma-AApeptides with potent and broad-spectrum activity, including clinically
      relevant strains that are unresponsive to most antibiotics. They are also not
      prone to select for drug-resistance.

PMID- 21963628
TI  - A new way for synthesis of phenoxazine and diphenoxazine derivatives via
      electrochemical method.
AB  - Electrochemical oxidation of hydroquinone (1a) and 2,3-dimethylhydroquinone (1b)
      have been studied in the presence of 2-aminophenol (3a) and 2-amino-4
      chlorophenol (3b), as nucleophiles in phosphate buffer solution (pH 7.2) using
      cyclic voltammetry and controlled potential coulometry. We proposed different
      mechanisms for the electrode process. The products were derived with good yield
      and purity using controlled-potential electrochemical oxidation of 1a, b in the
      presence of 3a and 3b at the graphite electrode in an undivided cell.

PMID- 21963629
TI  - Preparation and evaluation of orally rapidly disintegrating tablets containing
      taste-masked particles using one-step dry-coated tablets technology.
AB  - In this study, in order to address the problems with manufacturing orally rapidly
      disintegrating tablets (ODT) containing functional (taste masking or controlled
      release) coated particles, such as the low compactability of coated particles and
      the rupture of coated membrane during compression, a novel ODT containing taste
      masked coated particles (TMP) in the center of the tablets were prepared using
      one-step dry-coated tablets (OSDrC) technology. As a reference, physical-mixture
      tablets (PM) were prepared by a conventional tableting method, and the properties
      of the tablets and the effect of compression on the characteristics of TMP were
      evaluated. OSDrC was found to have higher tensile strength and far lower
      friability than PM, but the oral disintegration time of OSDrC is slightly longer
      than that of PM following high compression pressure. Consequently, OSDrC
      approaches the target tablet properties of ODT, whereas PM does not. The
      deformation of TMP in OSDrC due to compression is slight, and the release rate of
      acetaminophen (AAP) from OSDrC is the same as from TMP. However, TMP on the
      surface of PM are considerably deformed, and the release rate of AAP from PM is
      faster than from TMP. These findings suggest that OSDrC technology is a useful
      approach for preparing ODT containing functional coated particles. Furthermore,
      we demonstrate that the elastic recovery of tablets can affect differences in the
      properties of OSDrC, PM and placebo tablets (PC).

PMID- 21963630
TI  - Properties of gastroretentive sustained release tablets prepared by combination
      of melt/sublimation actions of L-menthol and penetration of molten polymers into
      tablets.
AB  - A novel floating sustained release tablet having a cavity in the center was
      developed by utilizing the physicochemical properties of L-menthol and the
      penetration of molten hydrophobic polymer into tablets. A dry-coated tablet
      containing famotidine as a model drug in outer layer was prepared with a L
      menthol core by direct compression. The tablet was placed in an oven at 80
      degrees C to remove the L-menthol core from tablet. The resulting tablet was then
      immersed in the molten hydrophobic polymers at 90 degrees C. The buoyancy and
      drug release properties of tablets were investigated using United States
      Pharmacopeia (USP) 32 Apparatus 2 (paddle 100 rpm) and 900 ml of 0.01 N HCl. The
      L-menthol core in tablets disappeared completely through pathways in the outer
      layer with no drug outflows when placed in an oven for 90 min, resulting in a
      formation of a hollow tablet. The hollow tablets floated on the dissolution media
      for a short time and the drug release was rapid due to the disintegration of
      tablet. When the hollow tablets were immersed in molten hydrophobic polymers for
      1 min, the rapid drug release was drastically retarded due to a formation of wax
      matrices within the shell of tablets and the tablets floated on the media for at
      least 6 h. When Lubri wax(r) was used as a polymer, the tablets showed the
      slowest sustained release. On the other hand, faster sustained release properties
      were obtained by using glyceryl monostearate (GMS) due to its low hydrophobic
      nature. The results obtained in this study suggested that the drug release rate
      from floating tablets could be controlled by both the choice of hydrophobic
      polymer and the combined use of hydrophobic polymers.

PMID- 21963631
TI  - 1,4-Diselenophene-1,4-diketone triggers caspase-dependent apoptosis in human
      melanoma A375 cells through induction of mitochondrial dysfunction.
AB  - Epidemiological, preclinical and clinical studies have supported the role of
      selenocompounds as potential cancer chemopreventive and chemotherapeutic agents.
      In this study, a novel selenophene-based compound, 1,4-diselenophene-1,4-diketone
      (DSeD), has been synthesized by Double Friedel-Crafts reaction and identified as
      a potent antiproliferative agent against a panel of six human caner cell lines.
      Despite this potency, DSeD was relatively nontoxic toward human normal cells,
      HS68 fibroblasts and HK-2 kidney cells. These results suggest that DSeD possesses
      great selectivity between cancer and normal cells. Induction of apoptosis in
      human melanoma A375 cells by DSeD was evidenced by accumulation of sub-G1 cell
      population, DNA fragmentation and nuclear condensation. Activation of caspase-9
      and depletion of mitochondrial membrane potential indicated the initiation of the
      mitochondria-mediated apoptosis pathway. Pretreatment of cells with general
      caspase inhibitor z-VAD-fmk and caspase-9 inhibitor z-LEHD-fmk significantly
      suppressed the cell apoptosis, demonstrating the important roles of caspase and
      mitochondria in DSeD-induced apoptotic cell death. Furthermore, DSeD-induced
      apoptosis was found independent of reactive oxygen species generation. Taken
      together, our results suggest that DSeD induces caspase-dependent apoptosis in
      A375 cells through activation of mitochondria-mediated apoptosis pathway.

PMID- 21963632
TI  - A novel series of (S)-2,7-substituted-1,2,3,4-tetrahydroisoquinoline-3-carboxylic
      acids: peroxisome proliferator-activated receptor alpha/gamma dual agonists with
      protein-tyrosine phosphatase 1B inhibitory activity.
AB  - Novel 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives were
      synthesized and (S)-7-(2-{2-[(E)-2-cyclopentylvinyl]-5-methyloxazol-4-yl}ethoxy)
      2-[(2E,4E)-hexadienoyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (14c)
      was identified as a peroxisome proliferator-activated receptor (PPAR) alpha/gamma
      dual agonist. The transactivation activity of 14c was comparable to that of
      rosiglitazone in human PPARgamma (EC50=0.14 uM) and was much higher than in human
      PPARalpha (EC50=0.20 uM). In addition, 14c, but not rosiglitazone, showed human
      protein-tyrosine phosphatase 1B (PTP-1B) inhibitory activity (IC50=1.85 uM). 14c
      showed about 10-fold stronger hypoglycemic and hypotriglyceridemic effects than
      rosiglitazone by repeated application for 14 d in male KK-Ay mice. Furthermore,
      14c, but not rosiglitazone, increased hepatic peroxisome acyl CoA oxidase
      activity at 30 mg/kg/d for 7 d in male Syrian hamsters, probably due to its
      PPARalpha agonist activity. 14c did not affect plasma volume at 100 mg/kg/d for
      14 d in male ICR mice, while rosiglitazone significantly increased it. In
      conclusion, 14c is a promising candidate for an efficacious and safe anti
      diabetic drug with triple actions as a PPARalpha/gamma dual agonist with PTP-1B
      inhibitory activity.

PMID- 21963633
TI  - Six new cycloartane glycosides from cimicifuga rhizome.
AB  - Three new 15-hydroxy-trinor type (1-3), a new tetranor type (4), and two new
      3,15,23,24-tetrahydroxy-16-oxo type cycloartane glycosides (5, 6) were isolated
      from the rhizome of Cimicifuga heracleifolia KOMAROV. Their structures were
      determined by the use of the 2D-NMR techniques and chemical evidence.

PMID- 21963634
TI  - Spirocyclic acylphloroglucinol derivatives from Hypericum beanii.
AB  - Four new acylphloroglucinols with an unusual 6/6/5 spirocyclic skeleton,
      hyperbeanols A-D (1-4), were isolated from the methanol extract of Hypericum
      beanii along with 16 known compounds. Their structures were established on the
      basis of spectroscopic and X-ray diffraction analysis. Hyperbeanols A-C were
      three stereoisomers different only at the relative configuration of C-4 and C-13,
      which were distinguished by the nuclear Overhauser effect spectroscopy (NOESY)
      spectroscopic data in combination with the single X-ray analysis of hyperbeanol A
      (1). The cytotoxic activity of hyperbeanols A-D against the cancer cell lines SK
      BR-3, HL-60, SMMC-7721, PANC-1, MCF-7, and K562 was also evaluated.

PMID- 21963635
TI  - Computational analysis on the binding of epitope peptide to human leukocyte
      antigen class I molecule A*2402 subtype.
AB  - Immunological response induced by small amino peptide has attracted much recent
      attention in the field of immunotherapy. Wilms' tumor (WT1) protein is one of the
      potent tumor antigens inducing immunological response in mouse and human, because
      WT1 is over expressed in many types of leukemia and various kinds of solid
      tumors. A 9-mer peptide encoded in WT1 protein (CMTWNQMNL; amino acid 235-243) is
      known to serve as antigenic peptide for human leukocyte antigen (HLA)-A*2402
      molecule. It was reported that the replacement of the second amino residue, which
      is deeply responsible for the peptide binding to HLA, induced strong
      immunological response compared to the natural peptide. In this study, 19 kinds
      of single amino substitutions were introduced at position 2 of this 9-mer WT1
      peptide. We performed molecular dynamics simulation on the complex of each of WT1
      epitope peptides and HLA-beta2 micro globulin (beta2m) molecule, and subsequently
      estimated the binding affinity using molecular mechanics/generalized-Born surface
      area method combined with normal mode analysis. Our computation indicated that
      the peptide containing M2Y or M2W mutation showed high binding affinity to the
      HLA-beta2m molecule as well as the natural peptide. We have also examined the
      role of the residue at position 2 in peptide binding to HLA-beta2m. The
      calculation showed that van der Waals interaction between the side chain of the
      residue at position 2 and hydrophobic residues inside B-pocket of HLA are
      important. These findings will be helpful to search other potent peptides that
      will enhance strong immunological response specific to HLA-A*2402 molecule.

PMID- 21963636
TI  - Drug penetration of the posterior eye tissues after topical instillation: in vivo
      and in silico simulation.
AB  - The purpose of this study was to analyze drug pharmacokinetics in the posterior
      eye tissues after topical instillation. For the in vivo study, the concentrations
      of ofloxacin in rabbit ocular tissues were analyzed by high performance liquid
      chromatography at 1, 2, and 3 h after instillation. For the in silico simulation,
      the concentration distribution of ofloxacin in the eye was calculated by the
      ocular pharmacokinetic model based on the diffusion/partition model. The
      simulated profiles were then compared with the in vivo experimental findings. In
      the in vivo study, the drug concentration in the posterior vitreous body
      initially decreased with time after topical instillation, and thereafter, the
      concentration increased. The in silico simulation of ocular pharmacokinetics
      indicated that the drug penetration of the posterior vitreous body was determined
      by three major pathways: (1) the initial transscleral penetration, (2) the
      intermediate transcorneal penetration, and (3) the late transretinal penetration.
      The in vivo findings were well described by a series of contributions by these
      three pathways. In conclusion, the present in vivo and in silico studies suggest
      that the instilled drugs initially reached the posterior vitreous body by
      diffusion through the sclera and then later by corneal penetration and systemic
      circulation.

PMID- 21963637
TI  - Discovery of a potent and orally available acyl-CoA: cholesterol acyltransferase
      inhibitor as an anti-atherosclerotic agent: (4-phenylcoumarin)acetanilide
      derivatives.
AB  - Acyl-CoA: cholesterol acyltransferase (ACAT) is an intracellular enzyme that
      catalyzes cholesterol esterification. ACAT inhibitors are expected to be potent
      therapeutic agents for the treatment of atherosclerosis. A series of potent ACAT
      inhibitors based on an (4-phenylcoumarin)acetanilide scaffold was identified.
      Evaluation of the structure-activity relationships of a substituent on this
      scaffold, with an emphasis on improving the pharmacokinetic profile led to the
      discovery of 2-[7-chloro-4-(3-chlorophenyl)-6-methyl-2-oxo-2H-chromen-3-yl]-N-[4
      chloro-2-(trifluoromethyl)phenyl]acetamide (23), which exhibited potent ACAT
      inhibitory activity (IC50=12 nM) and good pharmacokinetic profile in mice.
      Compound 23 also showed regressive effects on atherosclerotic plaques in
      apolipoprotein (apo)E knock out (KO) mice at a dose of 0.3 mg/kg per os (p.o.).

PMID- 21963638
TI  - Myrseguinosides A-E, five new glycosides from the fruits of Myrsine seguinii.
AB  - Chemical investigation of the 1-BuOH soluble fraction of the dried fruits of
      Myrsine seguinii (Myrsinaceae) led to the isolation of five new glycosides, named
      myrseguinosides A-E (1-5), together with eight known compounds (6-13). The
      absolute structures of the new glycosides were elucidated by spectroscopic and
      chemical analyses to be a monoterpene glucoside (1), two flavonol glycosides (2,
      3), and two oleanane-type triterpene saponins (4, 5). Myrseguinosides B (2), D
      (4), and E (5) exhibited 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging
      activity and growth inhibitory activity toward human cancer cells, respectively.

PMID- 21963639
TI  - Spicachlorantins G-J, new lindenane sesquiterpenoid dimers from the roots of
      Chloranthus spicatus.
AB  - Four new lindenane sesquiterpenoid dimers, spicachlorantins G-J (1-4), were
      isolated from the roots of Chloranthus spicatus together with seven known
      compounds, including chloramultilide A, shizukaol B, shizukaol D, shizukaol F,
      shizukaol P, chlorahololide D, and cycloshizukaol A. The planar structures of the
      new compounds were established by 1D-, 2D-NMR, and MS analyses. The absolute
      configurations of these compounds were determined by analyzing rotating
      Overhauser enhancement and exchange spectroscopy (ROESY) and circular dichroism
      (CD) spectra.

PMID- 21963640
TI  - Identification of indoline-2-thione analogs as novel potent inhibitors of alpha
      melanocyte stimulating hormone induced melanogenesis.
AB  - Based on the hits, 3,4-dihydroquinazoline-2-thione (1) and benzimidazole-2-thione
      (2), a series of indole-2-thione (3) and indole-2-thiol inhibitors (4) of
      melanogenesis were designed, synthesized and evaluated in melanoma B16 cells
      under the stimulant of alpha-melanocyte stimulating hormone (alpha-MSH). The
      indole-2-thione compounds (3a-g) exhibited an effective inhibitory activity on
      melanin synthesis. The Structure-Activity Relationship (SAR) studies of 2 have
      revealed that in potent inhibitor 3a (>100% inhibition at 30 uM, IC50=1.40 uM)
      the role of nitrogen (3-N) at 3-position is insignificance. In addition, the
      hydrophobic substituents of 3 were better than the hydrophilic one. However,
      conversion of thione (-C=S, 3) to thiol (-C-SH, 4) led to decrease in the
      potency.

PMID- 21963641
TI  - One-pot synthesis of benzo[f]indole-4,9-diones from 1,4-naphthoquinones and
      terminal acetylenes.
AB  - In this paper, a concise one-pot method for the construction of benzo[f]indole
      4,9-dione motifs is described. These transformations proceed via a sequential
      palladium- and copper-catalyzed coupling reaction of 1,4-naphthoquinones with
      terminal acetylenes, followed by a copper-catalyzed intramolecular cyclization
      reaction of the resulting coupling product.

PMID- 21963642
TI  - Bioactive C15 acetogenins from the red alga Laurencia obtusa.
AB  - The petroleum ether extract of the red alga Laurencia obtusa afforded three new
      C(15) acetogenins (cyclic ether enyne): (12Z)-cis-maneonene-D (1), (12E)-cis
      maneonene-E (2), and (12Z)-trans-maneonene-C (3), along with one known cis
      maneonene-A (4). Blood neutrophils were prepared, cultured, and incubated for 24,
      48, and 72 h in medium with and without isolated compounds. Blood neutrophils
      were prepared, cultured, and incubated for 24, 48 and 72 h in medium with and
      without the isolated compounds. Both morphology and DNA fragmentation methods
      assessed the percentage of neutrophils apoptosis in each culture. In the present
      study, several observations have been made concerning the apoptosis-inducing or
      inhibiting effect of 1 and 2. Both compounds had no inhibition of apoptosis but
      apoptosis was enhanced significantly by aging. However, 1 stimulated apoptosis of
      normal only at the initial 24 h. After that there was no significant difference
      in apoptosis with or without compound 1, while 2 stimulated apoptosis at all the
      times. The apoptosis induced by these two compounds was demonstrated by DNA
      fragmentation assay and microscopic observation. These observations suggest that
      compounds 1 and 2 may be involved in regulation of programmed death in the
      initiation and propagation of inflammatory responses.

PMID- 21963643
TI  - Molecular states of p-dimethylaminobenzonitrile coground with beta-cyclodextrin
      investigated using solid-state fluorescence spectroscopy.
AB  - Changes in molecular states of p-dimethylaminobenzonitrile (DMABN) coground with
      beta-cyclodextrin (beta-CD) were examined using solid-state fluorescence
      measurements. Formation of a DMABN/beta-CD inclusion complex by coprecipitation
      was confirmed by powder X-ray diffraction measurement. The powder X-ray
      diffraction pattern of the ground mixture was a halo pattern and differed from
      the pattern of the mixture prepared by coprecipitation. Solid-state fluorescence
      measurements revealed emission by DMABN crystals in a twisted intermolecular
      charge-transfer state at 473 nm. DMABN in the DMABN/beta-CD coprecipitate had a
      fluorescence emission peak at 393 nm due to its planar structure. In contrast,
      DMABN in a DMABN/beta-CD ground mixture had an emission peak at 473 nm due to its
      twisted structure. Grinding time-dependent structural changes in DMABN were
      evaluated using fluorescence lifetime and relative quantum yield measurements.
      Structural changes in DMABN in the DMABN/beta-CD coprecipitate from a planar to a
      twisted structure were observed with grinding. DMABN, dispersed in
      microcrystalline cellulose (CC) molecules in a DMABN/CC ground mixture, had a
      fluorescence emission peak at 473 nm. However, the excitation spectrum of a
      DMABN/beta-CD ground mixture differed from that of DMABN in CC. These results
      indicated that the molecular state of DMABN accommodated in the beta-CD cavity
      differs between the coprecipitate and the ground mixture.

PMID- 21963644
TI  - Dyscusins A-C, three new steroids from the leaves of Dysoxylum cumingianum.
AB  - Three new steroids dyscusins A-C (1-3), including a stigmastane-type sterol and
      two pregnanes, together with two known steroids were isolated from the leaves of
      Dysoxylum cumingianum (Meliaceae). Their structures were elucidated on the basis
      of extensive spectroscopic analyses. In a cytotoxicity assay, compound 1 showed
      ten-fold enhanced cytotoxicity against multi-drug resistant cancer cells (KB-C2)
      in the presence of 2.5 uM colchicine as compared with the absence of colchicine.
      This notable finding indicated that 1 possessed a multi-drug resistant reversal
      effect.

PMID- 21963645
TI  - Synthesis of new Galbeta1->4Fuc segments useful for biological investigations.
AB  - Useful segments (1, 2) for chemical probes embedded in a Galbeta1->4Fuc unit were
      designed and prepared for characterizing sugar-binding proteins in Caenorhabditis
      elegans. Segment 1 with an amino group terminus was used as a recognition unit in
      affinity chromatography. It was revealed that some proteins (annexins and
      galectins) in C. elegans have an affinity for Galbeta1->4Fuc.

PMID- 21963646
TI  - Halioxepine, a new meroditerpene from an Indonesian sponge Haliclona sp.
AB  - Chemical investigations on a sponge Haliclona sp. found a meroditerpene 1 having
      a new carbon skeleton. By analyzing spectroscopic data, the structure was
      elucidated to comprise a substituted hydroquinone, a tetrahydrooxepine, and a
      cyclohexene, and these components were united with C1 and C2 units. Compound 1
      showed moderate cytotoxicity against NBT-T2 cells with IC50 4.8 ug/ml and also
      antioxidant activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) with IC50 3.2
      ug/ml.

PMID- 21963647
TI  - Identification of mutaprodenafil in a dietary supplement and its subsequent
      synthesis.
AB  - We isolated a new illegal sildenafil analogue named mutaprodenafil from a dietary
      supplement for erectile dysfunction (ED) and proposed that it is an aildenafil
      derivative containing an imidazole moiety. We subsequently synthesized
      mutaprodenafil from a thioaildenafil and authenticated its structure.

PMID- 21963648
TI  - Therapeutic effects of PEGylated insulin-like growth factor I in the pmn mouse
      model of motoneuron disease.
AB  - Based on its potent neurotrophic and myotrophic activities, insulin-like growth
      factor I (IGF-I) has been proposed for treatment of neuromuscular disorders such
      as muscular dystrophies and amyotrophic lateral sclerosis (ALS). However, the
      short half life in the circulation limits its use in vivo. At least in mouse
      models, beneficial effects are generally only observed by dosing regimens such as
      minipumps or gene therapy that are difficult to translate to patients. We have
      developed a polyethylene glycol coupled IGF-I (PEG-IGF-I) that could circumvent
      these problems by longer half-life, showing all features of a therapeutic agent
      supporting muscular and neuronal function. Here we investigated its effects in
      the pmn mutant mouse, a model with typical dying-back motoneuron degeneration. In
      vitro, PEG-IGF-I and rhIGF-I profoundly promoted survival axonal growth of wild
      type as well as pmn mutant embryonic motoneurons, suggesting that PEG-IGF-I had a
      fully conserved neurotrophic activity via its receptor. In vivo, treatment of pmn
      mutant mice with PEG-IGF-I prolonged survival, protected against late stage
      weight loss and significantly maintained muscle force and motor coordination.
      Consistently, PEG-IGF-I treatment rescued facial and lumbar motoneurons from cell
      death and partially preserved phrenic nerve myelinated axons. The data support
      that PEG-IGF-I could be used for treatment of neuromuscular diseases in a
      clinically feasible manner.

PMID- 21963649
TI  - In vivo monitoring of recovery from neurodegeneration in conditional transgenic
      SCA1 mice.
AB  - Reliable and objective markers of neuronal function and pathology that can
      directly assess the effects of neuroprotective treatments in the brain are
      urgently needed for clinical trials in neurodegenerative diseases. Here we
      assessed the sensitivity of high field proton magnetic resonance spectroscopy
      ((1)H MRS) to monitor reversal of neurodegeneration by taking advantage of a well
      characterized conditional mouse model of spinocerebellar ataxia type 1 (SCA1),
      where the cerebellar pathology and ataxic phenotype are reversible by doxycycline
      administration. Transgene expression was suppressed by feeding the mice with chow
      that contains doxycycline from 6 to 12 weeks of age in an early stage group and
      from 12 to 24 weeks in a mid-stage group. Cerebellar neurochemical profiles of
      treated and untreated conditional mice were measured at 9.4 tesla (T) before and
      after treatment and compared to those of wild type (WT) controls, as well as to
      histology measures (molecular layer thickness in the primary fissure and a global
      pathological severity score). Concentrations of N-acetylaspartate (NAA) and myo
      inositol in the treated mice trended toward normalization to WT levels in both
      the early and mid-stage groups. The NAA-to-myo-inositol ratio was significantly
      different between the treated vs. untreated SCA1 mice and demonstrated partial
      reversal to WT values both at early and mid-stage, consistent with the
      histological measures. Taurine and total creatine levels were completely
      normalized in early and mid-stage treatment groups, respectively. The MRS markers
      were a more sensitive measure of treatment response than the histological
      measures from the same volume-of-interest in the early stage group. NAA, myo
      inositol and taurine levels were significantly correlated with the histology
      measures in data combined from all groups. These data demonstrate that MRS
      markers reliably detect rescue from neuronal pathology and imply that the
      neurochemical levels measured by MRS accurately reflect treatment efficacy.
      Therefore this study presents an important step in validating MRS biomarkers as
      potential surrogate markers to evaluate therapeutics in pre-clinical and clinical
      trials in SCA1.

PMID- 21963650
TI  - Rac1-regulated dendritic spine remodeling contributes to neuropathic pain after
      peripheral nerve injury.
AB  - Although prior studies have implicated maladaptive remodeling of dendritic spines
      on wide-dynamic range dorsal horn neurons as a contributor to pain after spinal
      cord injury, there have been no studies on dendritic spines after peripheral
      nerve injury. To determine whether dendritic spine remodeling contributes to
      neuronal hyperexcitability and neuropathic pain after peripheral nerve injury, we
      analyzed dendritic spine morphology and functional influence in lamina IV-V
      dorsal horn neurons after sham, chronic constriction injury (CCI) of the sciatic
      nerve, and CCI treatment with NSC23766, a selective inhibitor of Rac1, which has
      been implicated in dendritic spine development. 10 days after CCI, spine density
      increased with mature, mushroom-shaped spines preferentially distributed along
      dendritic branch regions closer to the cell body. Because spine morphology is
      strongly correlated with synaptic function and transmission, we recorded the
      response of single units to innocuous and noxious peripheral stimuli and
      performed behavioral assays for tactile allodynia and thermal hyperalgesia. Wide
      dynamic range dorsal horn neurons of CCI animals exhibited hyperexcitable
      responses to a range of stimuli. They also showed reduced nociceptive thresholds
      in the ipsilateral hind paw. 3-day treatment with NSC23766 significantly reduced
      post-CCI spine dimensions and densities, and attenuated injury-induced
      hyperexcitability. Drug treatment reduced behavioral measures of tactile
      allodynia, but not for thermal hyperalgesia. Together, our results demonstrate
      that peripheral nerve injury induces Rac1-regulated remodeling of dendritic
      spines on dorsal horn neurons, and suggest that this spine remodeling contributes
      to neuropathic pain.

PMID- 21963651
TI  - Absence of SOD1 leads to oxidative stress in peripheral nerve and causes a
      progressive distal motor axonopathy.
AB  - Oxidative stress is commonly implicated in the pathogenesis of motor neuron
      disease. However, the cause and effect relationship between oxidative stress and
      motor neuron degeneration is poorly defined. We recently identified denervation
      at the neuromuscular junction in mice lacking the antioxidant enzyme, Cu,Zn
      superoxide dismutase (SOD1) (Fischer et al., 2011). These mice show a phenotype
      of progressive muscle atrophy and weakness in the setting of chronic oxidative
      stress. Here, we investigated further the extent of motor neuron pathology in
      this model, and the relationship between motor pathology and oxidative stress. We
      report preferential denervation of fast-twitch muscles beginning between 1 and 4
      months of age, with relative sparing of slow-twitch muscle. Motor axon terminals
      in affected muscles show widespread sprouting and formation of large axonal
      swellings. We confirmed, as was previously reported, that spinal motor neurons
      and motor and sensory nerve roots in these mice are preserved, even out to 18
      months of age. We also found preservation of distal sensory fibers in the
      epidermis, illustrating the specificity of pathology in this model for distal
      motor axons. Using HPLC measurement of the glutathione redox potential, we
      quantified oxidative stress in peripheral nerve and muscle at the onset of
      denervation. SOD1 knockout tibial nerve, but not gastrocnemius muscle, showed
      significant oxidation of the glutathione pool, suggesting that axonal
      degeneration is a consequence of impaired redox homeostasis in peripheral nerve.
      We conclude that the SOD1 knockout mouse is a model of oxidative stress-mediated
      motor axonopathy. Pathology in this model primarily affects motor axon terminals
      at the neuromuscular junction, demonstrating the vulnerability of this synapse to
      oxidative injury.

PMID- 21963652
TI  - PET imaging for attention deficit preclinical drug testing in neurofibromatosis-1
      mice.
AB  - Attention system abnormalities represent a significant barrier to scholastic
      achievement in children with neurofibromatosis-1 (NF1). Using a novel mouse model
      of NF1-associated attention deficit (ADD), we demonstrate a presynaptic defect in
      striatal dopaminergic homeostasis and leverage this finding to apply [(11)C]
      raclopride positron-emission tomography (PET) in the intact animal. While
      methylphenidate and l-Deprenyl correct both striatal dopamine levels on PET
      imaging and defective attention system function in Nf1 mutant mice, pharmacologic
      agents that target de-regulated cyclic AMP and RAS signaling in these mice do
      not. These studies establish a robust preclinical model to evaluate promising
      agents for NF1-associated ADD.

PMID- 21963653
TI  - Niaspan enhances vascular remodeling after stroke in type 1 diabetic rats.
AB  - We investigated the changes and the molecular mechanisms of cerebral vascular
      damage and tested the therapeutic effects of Niaspan in type-1 streptozotocin
      induced diabetic (T1DM) rats after stroke. T1DM-rats were subjected to transient
      middle cerebral artery occlusion (MCAo) and treated without or with Niaspan. Non
      streptozotocin rats (WT) were also subjected to MCAo. Functional outcome, blood
      brain-barrier (BBB) leakage, brain hemorrhage, immunostaining, and rat brain
      microvascular endothelial cell (RBEC) culture were performed. Compared to WT-MCAo
      rats, T1DM-MCAo-rats did not show an increase lesion volume, but exhibited
      significantly increased brain hemorrhage, BBB leakage and vascular damage as well
      as decreased functional outcome after stroke. Niaspan treatment of stroke in T1DM
      MCAo-rats significantly attenuated BBB damage, promoted vascular remodeling and
      improved functional outcome after stroke. T1DM-MCAo-rats exhibited significantly
      increased Angiopoietin 2 (Ang2) expression, but decreased Ang1 expression in the
      ischemic brain compared to WT-MCAo-rats. Niaspan treatment attenuated Ang2, but
      increased Ang1 expression in the ischemic brain in T1DM-MCAo-rats. In vitro data
      show that the capillary-like tube formation in the WT-RBECs marginally increased
      compared to T1DM-RBEC. Niaspan and Ang1 treatment significantly increased tube
      formation compared to non-treatment control. Inhibition of Ang1 attenuated Niacin
      induced tube formation in T1DM-RBECs. Niaspan treatment of stroke in T1DM-rats
      promotes vascular remodeling and improves functional outcome. The Ang1/Ang2
      pathway may contribute to Niaspan induced brain plasticity. Niaspan warrants
      further investigation as a therapeutic agent for the treatment of stroke in
      diabetics.

PMID- 21963655
TI  - Circadian mRNA expression of coagulation and fibrinolytic factors is organ
      dependently disrupted in aged mice.
AB  - To evaluate the effects of aging on the circadian gene expression of coagulation
      and fibrinolytic factors in the mouse tissues, we examined temporal mRNA
      expression profiles of plasminogen activator inhibitor-1 (PAI-1), tissue-type
      plasminogen activator (tPA), tissue factor (TF), and thrombomodulin (TM) genes
      together with circadian clock genes in the brains, hearts and livers of young
      (5weeks old) and aged (15months old) mice. Cardiac mRNA expression of beta-myosin
      heavy chain (beta-MHC), a molecular marker of cardiac hypertrophy, was obviously
      increased in the aged mice. Rhythmic expression of the clock genes mPer2 and
      BMAL1 in these organs was almost identical between young and aged mice, whereas
      that of PAI-1, TF and TM mRNAs and of clock-controlled genes such as DBP and Dec1
      were damped to low levels in the livers of aged mice. Expression levels of tPA
      mRNA were significantly decreased and those of TF were significantly elevated
      throughout the day in the brain of aged mice. Expression levels of PAI-1 in the
      heart of aged mice were continuously elevated over 2-fold the peak levels of
      young mice throughout the day. However, day/night fluctuations in plasma PAI-1
      levels were unaffected by aging. Aging tissue- and time-dependently affects the
      mRNA expression of coagulation and fibrinolytic factors. Aging-dependent
      constitutive PAI-1 induction in the heart might be a risk factor for
      cardiovascular diseases that is independent of plasma PAI-1 levels.

PMID- 21963654
TI  - Genetic elimination of alpha3(IV) collagen fails to rescue anti-collagen B cells.
AB  - Organ deposition of autoantibodies against the noncollagenous-1 domain of the
      alpha3 chain of type IV collagen leads to severe kidney and lung injury in anti
      glomerular basement membrane disease. The origin and regulation of these highly
      pathogenic autoantibodies remains unknown. Anti-alpha3(IV) collagen B lymphocytes
      are predicted to mature in vivo ignorant of target antigen because alpha3(IV)
      collagen expression is highly tissue restricted and pathogenic epitopes are
      cryptic. However, a recent analysis of an anti-alpha3(IV)NC1 collagen
      autoantibody transgenic mouse model revealed that developing B cells are rapidly
      silenced by deletion and editing in the bone marrow. To dissect the role of
      collagen as central tolerogen in this model, we determined B cell fate in
      autoantibody transgenic mice genetically lacking alpha3(IV) collagen. We found
      that absence of the tissue target autoantigen has little impact on the fate of
      anti-alpha3(IV)NC1 B cells. This implies a more complex regulatory mechanism for
      preventing anti-glomerular basement membrane disease than has been previously
      considered, including the possibility that a second antigen present in bone
      marrow engages and tolerizes anti-alpha3(IV)NC1 collagen B cells.

PMID- 21963656
TI  - Storage stability of biocrude oils from fast pyrolysis of poultry litter.
AB  - The unstable nature of biocrude oils produced from conventional pyrolysis of
      biomass is one of the properties that limits its application. In the disposal of
      poultry litter via pyrolysis technology, the biocrude oil produced as a value
      added product can be used for on farm applications. In this study, we
      investigated the influence of bedding material (wood shavings) on the storage
      stability of biocrude oils produced from the fast pyrolysis of poultry litter.
      The biocrude oils produced from manure, wood (pine and oak), and mixtures of
      manure and wood in proportions (75:25 50:50, and 25:75w/w%) were stored under
      ambient conditions in sealed glass vials for a period of 6 months and their
      stability were monitored by measuring the changes in viscosity over time. The
      manure oil had the lowest rate of viscosity change and thus was relatively the
      most stable and the oils from the 50:50w/w% litter mixtures were the least
      stable. The rate of viscosity change of the manure biocrude oil was 1.33cP/day
      and that of the 50/50 litter mixture was 7.6cP/day for pine and 4.17cP/day for
      oak. The spectrometric analyses of the biocrude oils showed that the presence of
      highly reactive oxygenated functionalities in the oil were responsible for the
      instability characteristic of the litter biocrude oils. The poor stability of the
      biocrude oil from the 50:50w/w% litter mixtures was attributed to reactions
      between nitrogenous compounds (amides) from protein degradation and oxygenated
      compounds from the decomposition of polysaccharides and lignin. The addition of
      10% methanol and 10% ethanol to the oil from 50% manure and 50% pine reduced the
      initial viscosity of the oil and was also beneficial in slowing down the rate of
      viscosity change during storage.

PMID- 21963657
TI  - Artificial lightweight aggregates as utilization for future ashes - A case study.
AB  - In the future, more electricity in the Netherlands will be produced using coal
      with co-combustion. Due to this, the generated annual ash volume will increase
      and the chemical composition will be influenced. One of the options for
      utilization if present markets are saturated and for use of fly ashes with
      different compositions, is as raw material for lightweight aggregates. This was
      selected as one of the best utilizations options regarding potential ash volume
      to be applied, environmental aspects and status of technology. Because of this, a
      study has been performed to assess the potential utilization of fly ash for the
      production of lightweight aggregate. Lightweight aggregate has been produced in a
      laboratory scale rotary kiln. The raw material consisted of class F fly ash with
      high free lime content. An addition of 8% clay was necessary to get green pellets
      with sufficient green strength. The basic properties of the produced lightweight
      aggregate and its behaviour in concrete have been investigated. The concrete has
      a good compressive strength and its leaching behaviour meets the most stringent
      requirements of Dutch environmental regulations. The carbon foot print of
      concrete will be negatively influenced if only the concrete itself is taken into
      account, but the reduction of the volume weight has advantages regarding design,
      transport emissions and isolation properties which may counteract this. In the
      Dutch situation the operational costs are higher than expected potential selling
      price for the LWA, which implies that the gate fee for the fly ash is negative.

PMID- 21963658
TI  - A novel method for obtaining semi-thin cross sections of the Drosophila heart and
      their labeling with multiple antibodies.
AB  - The Drosophila heart has become an exciting model for elucidating the molecular
      basis for cardiac function in higher organisms. To complement the genetic
      approaches that have recently identified an array of genes essential for cardiac
      function, we developed a method to obtain optimal semi-thin cross sections of
      embryonic, larval, and adult fly hearts in a desired orientation. A procedure for
      fluorescent labeling of these sections with multiple markers has also been
      developed, allowing the detection of proteins at high subcellular resolution.
      Sections obtained by our method reveal changes in cell shape between embryonic
      heart and aorta cardioblasts and elucidate the morphology of the adult heart.
      Analysis of the adult heart reveals the precise cardiac tube morphology,
      differential distribution of the extracellular matrix protein Laminin within the
      cardiac tube, as well as individual hand-positive, and Held Out Wings (HOW)
      positive luminal cells that might represent blood cells. In summary, our method
      enables visualization of cross sections of the embryonic and adult hearts at high
      resolution while maintaining the ability to co-label the sections with multiple
      markers, thereby facilitating the analysis of cardiac tube formation and
      maintenance at different developmental stages.

PMID- 21963659
TI  - Proportion of pet cats registered with a veterinary practice and factors
      influencing registration in the UK.
AB  - Registration of a cat with a veterinary practice is likely to be a critical
      factor for access to key preventative medicine. A cross-sectional study was
      conducted to collect data in the United Kingdom on the registration status of
      cats and potential explanatory variables. These data were also used to identify
      potential sources of bias associated with selecting controls from veterinary
      registered populations of cats due to differences between registered and
      unregistered cats. Cat owners reported that 13.6% (84/616) of their cats had not
      been registered with a veterinary practice since living at their current address.
      Multivariable logistic regression indicated that unregistered cats were
      significantly more likely than registered cats to be entire, to have not been
      vaccinated within the previous year, to be living in households in Northern
      Ireland and in households with an annual income <L10,000.(1) Whilst the neuter
      status and the vaccination status of the cat are likely to result from non
      registration, the household location and annual income are factors that can be
      used to inform future interventions designed to increase the proportion of
      veterinary registered cats.

PMID- 21963660
TI  - Negative-strand RNA viruses: the plant-infecting counterparts.
AB  - While a large number of negative-strand (-)RNA viruses infect animals and humans,
      a relative small number have plants as their primary host. Some of these have
      been classified within families together with animal/human infecting viruses due
      to similarities in particle morphology and genome organization, while others have
      just recently been/or are still classified in floating genera. In most cases, at
      least two striking differences can still be discerned between the animal/human
      infecting viruses and their plant-infecting counterparts which for the latter
      relate to their adaptation to plants as hosts. The first one is the capacity to
      modify plasmodesmata to facilitate systemic spread of infectious viral entities
      throughout the plant host. The second one is the capacity to counteract RNA
      interference (RNAi, also referred to as RNA silencing), the innate antiviral
      defence system of plants and insects. In this review an overview will be
      presented on the negative-strand RNA plant viruses classified within the families
      Bunyaviridae, Rhabdoviridae, Ophioviridae and floating genera Tenuivirus and
      Varicosavirus. Genetic differences with the animal-infecting counterparts and
      their evolutionary descendants will be described in light of the above processes.

PMID- 21963661
TI  - Biological feasibility of measles eradication.
AB  - Because of the success of global measles control programs, the World Health
      Organization (WHO), along with its partner agencies, is once again considering
      the possibility of setting a target date for measles eradication. Measles would
      be the fourth viral agent to be eradicated joining the successful programs to
      eradicate smallpox and rinderpest virus, and the continuing effort to eradicate
      polio virus. A description of the recent progress toward measles eradication was
      recently published as a supplement in the Journal of Infectious Diseases (15
      July, 2011, 204 (Suppl. 1)) and the reader is referred to this document for a
      detailed summary of the global status of measles control. This review will focus
      on the biologic and virologic aspects of measles eradication.

PMID- 21963662
TI  - Viral deletions among healthy young Chinese adults with occult hepatitis B virus
      infection.
AB  - To investigate the mechanism and prognosis of occult hepatitis B virus (HBV)
      infection (OBI) at a molecular level among healthy young adults, the presence of
      HBV DNA in 1176 sera samples collected from healthy young people after neonatal
      vaccination was assessed by nested polymerase chain reaction (PCR) using specific
      primers designed for the X and S regions of the HBV genome. Full-length HBV DNA
      from 9 patients with OBI (OB1-OB9) was cloned and sequenced. Deletions in the pre
      S, basal core promoter (BCP), core (C) and polymerase (P) regions were observed.
      The data indicate that there is still a substantial risk of OBI in China despite
      neonatal vaccination. All deletions that were observed in the pre-S, BCP, C and P
      regions play a direct or indirect role in OBI. The presence of a deletion
      mutation in the pre-S1 region was considered to play a pivotal role in
      hepatocarcinogenesis and was found to increase the risk of hepatocellular
      carcinoma in the cohorts studied.

PMID- 21963663
TI  - Structural insights into the rhabdovirus transcription/replication complex.
AB  - The rhabdoviruses have a non-segmented single stranded negative-sense RNA genome.
      Their multiplication in a host cell requires three viral proteins in addition to
      the viral RNA genome. The nucleoprotein (N) tightly encapsidates the viral RNA,
      and the N-RNA complex serves as the template for both transcription and
      replication. The viral RNA-dependent RNA polymerase is a two subunit complex that
      consists of a large subunit, L, and a non-catalytic cofactor, the phosphoprotein,
      P. P also acts as a chaperone of nascent RNA-free N by forming a N(0)-P complex
      that prevents N from binding to cellular RNAs and from polymerizing in the
      absence of RNA. Here, we discuss the recent molecular and structural studies of
      individual components and multi-molecular complexes that are involved in the
      transcription/replication complex of these viruses with regard to their
      implication in viral transcription and replication.

PMID- 21963664
TI  - Molecular epidemiology of human herpesvirus 8 variants in Kaposi's sarcoma from
      Iranian patients.
AB  - Kaposi's sarcoma (KS) is a rare cancer in Iran and there is no epidemiological
      and molecular information about HHV-8 variants circulating among the Iranian
      population. In this study HHV-8 sequences have been analyzed in 43 cutaneous KS
      biopsies from Iranian patients mainly affected by classic KS. DNA samples were
      subjected to PCR amplification of HHV-8 ORF26, T0.7 and K1 followed by direct
      nucleotide sequencing and phylogenetic analysis. The analysis of ORF26 showed
      that 30 (69.8%) and 13 (30.2%) samples belonged to subtypes A/C and K,
      respectively. In general, the clustering of HHV-8 T0.7 variants paralleled that
      of ORF26. Genotyping of K1 sequences showed that the majority of samples (39 out
      of 41) fall into the large C clade with only 2 belonging to the A clade. In
      conclusion, HHV-8 variants identified among classic Iranian KS are largely
      related to Eurasian genotypes previously identified in KS from Mediterranean,
      Middle East, and East Asian regions.

PMID- 21963665
TI  - LAX PANICLE2 of rice encodes a novel nuclear protein and regulates the formation
      of axillary meristems.
AB  - Aerial architecture in higher plants is dependent on the activity of the shoot
      apical meristem (SAM) and axillary meristems (AMs). The SAM produces a main shoot
      and leaf primordia, while AMs are generated at the axils of leaf primordia and
      give rise to branches and flowers. Therefore, the formation of AMs is a critical
      step in the construction of plant architecture. Here, we characterized the rice
      (Oryza sativa) lax panicle2 (lax2) mutant, which has altered AM formation. LAX2
      regulates the branching of the aboveground parts of a rice plant throughout plant
      development, except for the primary branch in the panicle. The lax2 mutant is
      similar to lax panicle1 (lax1) in that it lacks an AM in most of the lateral
      branching of the panicle and has a reduced number of AMs at the vegetative stage.
      The lax1 lax2 double mutant synergistically enhances the reduced-branching
      phenotype, indicating the presence of multiple pathways for branching. LAX2
      encodes a nuclear protein that contains a plant-specific conserved domain and
      physically interacts with LAX1. We propose that LAX2 is a novel factor that acts
      together with LAX1 in rice to regulate the process of AM formation.

PMID- 21963666
TI  - Tetrapyrrole synthesis of photosynthetic chromerids is likely homologous to the
      unusual pathway of apicomplexan parasites.
AB  - Most photosynthetic eukaryotes synthesize both heme and chlorophyll via a common
      tetrapyrrole biosynthetic pathway starting from glutamate. This pathway was
      derived mainly from cyanobacterial predecessor of the plastid and differs from
      the heme synthesis of the plastid-lacking eukaryotes. Here, we show that the
      coral-associated alveolate Chromera velia, the closest known photosynthetic
      relative to Apicomplexa, possesses a tetrapyrrole pathway that is homologous to
      the unusual pathway of apicomplexan parasites. We also demonstrate that, unlike
      other eukaryotic phototrophs, Chromera synthesizes chlorophyll from glycine and
      succinyl-CoA rather than glutamate. Our data shed light on the evolution of the
      heme biosynthesis in parasitic Apicomplexa and photosynthesis-related biochemical
      processes in their ancestors.

PMID- 21963668
TI  - Molecular profiling of stomatal meristemoids reveals new component of asymmetric
      cell division and commonalities among stem cell populations in Arabidopsis.
AB  - The balance between maintenance and differentiation of stem cells is a central
      question in developmental biology. Development of stomata in Arabidopsis thaliana
      begins with de novo asymmetric divisions producing meristemoids, proliferating
      precursor cells with stem cell-like properties. The transient and asynchronous
      nature of the meristemoid has made it difficult to study its molecular
      characteristics. Synthetic combination of stomatal differentiation mutants due to
      loss- or gain-of-function mutations in SPEECHLESS, MUTE, and SCREAM create
      seedlings with an epidermis overwhelmingly composed of pavement cells,
      meristemoids, or stomata, respectively. Through transcriptome analysis, we define
      and characterize the molecular signatures of meristemoids. The reporter
      localization studies of meristemoid-enriched proteins reveals pathways not
      previously associated with stomatal development. We identified a novel protein,
      POLAR, and demonstrate through time-lapse live imaging that it exhibits transient
      polar localization and segregates unevenly during meristemoid asymmetric
      divisions. The polar localization of POLAR requires BREAKING OF ASYMMETRY IN THE
      STOMATAL LINEAGE. Comparative bioinformatic analysis of the transcriptional
      profiles of a meristemoid with shoot and root apical meristems highlighted
      cytokinin signaling and the ERECTA family receptor-like kinases in the broad
      regulation of stem cell populations. Our work reveals molecular constituents of
      stomatal stem cells and illuminates a common theme among stem cell populations in
      plants.

PMID- 21963669
TI  - The bidirectional relationship of depression and diabetes: a systematic review.
AB  - Depression and diabetes are both serious chronic conditions common in Western
      cultures. These conditions impart a significant burden on the patients and
      society. Depression is often comorbid with chronic illness, and past research has
      found an increased prevalence of depressive symptoms in patients with Type 2
      Diabetes Mellitus (T2DM). However, the exact nature and direction of this
      relationship are unknown. Depression is often thought to be a consequence of
      diabetes, perhaps due to the burden of chronic illness. Research has also
      suggested that depression may be a risk factor for development of diabetes, in
      part due to biochemical changes in depression and in part because of a reduction
      of health care behaviors in individuals with depression. This paper reviews the
      literature behind both lines of investigation and includes special diagnostic and
      clinical considerations for at risk populations. We discuss clinical
      implications, limitations of current research, and areas of interest for future
      research.

PMID- 21963670
TI  - Controversy clarified: an updated review of clinical psychology and tele-health.
AB  - One of the most controversial topics in the field of clinical psychology, online
      tele-health, or the integration of computers and the internet with therapeutic
      techniques, remains at the forefront of many debates. Despite potential interest,
      there are numerous factors that a psychologist must consider before integrating
      an online tele-health intervention into their own practice. This article outlines
      literature pertinent to the debate. The article begins with a brief history of
      the use of non-face-to-face interventions as well as the earliest recorded use of
      "tele-health" before discussing the modern benefits and risks associated with
      usage. Considerations for the psychologist as well as the client are detailed;
      incorporating ethical implications. The authors conclude that the utilization of
      tele-health interventions is an exponentially expanding field that should
      continue to be explored. Despite many well-conceived studies, a psychologist
      should educate themselves in all aspects of the new modes of intervention (e.g.,
      ethical, legal, evidence-based treatments) before attempting to implement them
      into everyday practice. The article ends with a discussion on the acceptance
      among psychologists, as well as the outlook for the future.

PMID- 21963667
TI  - The JAZ proteins: a crucial interface in the jasmonate signaling cascade.
AB  - Jasmonates are phytohormones that regulate many aspects of plant growth,
      development, and defense. Within the signaling cascades that are triggered by
      jasmonates, the JASMONATE-ZIM DOMAIN (JAZ) repressor proteins play a central
      role. The endogenous bioactive JA-Ile conjugate mediates the binding of JAZ
      proteins to the F-box protein CORONATINE INSENSITIVE1 (COI1), part of the
      Skp1/Cullin/F-box SCF(COI1) ubiquitin E3 ligase complex. Upon the subsequent
      destruction of the JAZ proteins by the 26S proteasome, multiple transcription
      factors are relieved from JAZ-mediated repression, allowing them to activate
      their respective downstream responses. However, many questions remain regarding
      the targets, specificity, function, and regulation of the different JAZ proteins.
      Here, we review recent studies on the model plant Arabidopsis thaliana that
      provided essential and novel insights. JAZ proteins have been demonstrated to
      interact with a broad array of transcription factors that each control specific
      downstream processes. Recruitment of the corepressor TOPLESS unveiled a mechanism
      for JAZ-mediated gene repression. Finally, the presence of JAZ proteins was also
      found to be regulated by alternative splicing and interactions with proteins from
      other hormonal signaling pathways. Overall, these contemporary findings
      underscore the value of protein-protein interaction studies to acquire
      fundamental insight into molecular signaling pathways.

PMID- 21963671
TI  - Mood-as-input hypothesis and perseverative psychopathologies.
AB  - Mood-as-input hypothesis is a theory of task perseveration that has been applied
      to the understanding of perseveration across psychopathologies such as
      pathological worrying, compulsive checking, depressive rumination, and chronic
      pain. We review 10 years of published evidence from laboratory-based analogue
      studies and describe their relevance for perseveration in clinical populations.
      In particular, mood-as-input hypothesis predicts that perseveration at a task
      will be influenced by interactions between the individual's stop rules for the
      task and their concurrent mood, and that the valency of an individual's
      concurrent mood is used as information about whether the stop rule-defined goals
      for the task have been met. The majority of the published research is consistent
      with this hypothesis, and we provide evidence that clinical populations possess
      characteristics that would facilitate perseveration through mood-as-input
      processes. We argue that mood-as-input research on clinical populations is long
      overdue because (1) it has potential as a transdiagnostic mechanism helping to
      explain the development of perseveration and its comorbidity across a range of
      different psychopathologies, (2) it is potentially applicable to any
      psychopathology where perseveration is a defining feature of the symptoms, and
      (3) it has treatment implications for dealing with clinical perseveration.

PMID- 21963672
TI  - The PPAR alpha agonist gemfibrozil is an ineffective treatment for spinal cord
      injured mice.
AB  - Peroxisome Proliferator Activated Receptor (PPAR)-alpha is a key regulator of
      lipid metabolism and recent studies reveal it also regulates inflammation in
      several different disease models. Gemfibrozil, an agonist of PPAR-alpha, is a FDA
      approved drug for hyperlipidemia and has been shown to inhibit clinical signs in
      a rodent model of multiple sclerosis. Since many studies have shown improved
      outcome from spinal cord injury (SCI) by anti-inflammatory and neuroprotective
      agents, we tested the efficacy of oral gemfibrozil given before or after SCI for
      promoting tissue preservation and behavioral recovery after spinal contusion
      injury in mice. Unfortunately, the results were contrary to our hypothesis; in
      our first attempt, gemfibrozil treatment exacerbated locomotor deficits and
      increased tissue pathology after SCI. In subsequent experiments, the behavioral
      effects were not replicated but histological outcomes again were worse. We also
      tested the efficacy of a different PPAR-alpha agonist, fenofibrate, which also
      modulates immune responses and is beneficial in several neurodegenerative disease
      models. Fenofibrate treatment did not improve recovery, although there was a
      slight trend for a modest increase in histological tissue sparing. Based on our
      results, we conclude that PPAR-alpha agonists yield either no effect or worsen
      recovery from spinal cord injury, at least at the doses and the time points of
      drug delivery tested here. Further, patients sustaining spinal cord injury while
      taking gemfibrozil might be prone to exacerbated tissue damage.

PMID- 21963673
TI  - Respiratory function following bilateral mid-cervical contusion injury in the
      adult rat.
AB  - The consequences of spinal cord injury (SCI) are often viewed as the result of
      white matter damage. However, injuries occurring at any spinal level, especially
      in cervical and lumbar enlargement regions, also entail segmental neuronal loss.
      Yet, the contributions of gray matter injury and plasticity to functional
      outcomes are poorly understood. The present study addressed this issue by
      investigating changes in respiratory function following bilateral C(3)/C(4)
      contusion injuries at the level of the phrenic motoneuron (PhMN) pool which in
      the adult rat extends from C(3) to C(5/6) and provides innervation to the
      diaphragm. Despite extensive white and gray matter pathology associated with two
      magnitudes of injury severity, ventilation was relatively unaffected during both
      quiet breathing and respiratory challenge (hypercapnia). On the other hand,
      bilateral diaphragm EMG recordings revealed that the ability to increase
      diaphragm activity during respiratory challenge was substantially, and
      chronically, impaired. This deficit has not been seen following predominantly
      white matter lesions at higher cervical levels. Thus, the impact of gray matter
      damage relative to PhMNs and/or interneurons becomes evident during conditions
      associated with increased respiratory drive. Unaltered ventilatory behavior,
      despite significant deficits in diaphragm function, suggests compensatory
      neuroplasticity involving recruitment of other spinal respiratory networks which
      may entail remodeling of connections. Transynaptic tracing, using pseudorabies
      virus (PRV), revealed changes in PhMN-related interneuronal labeling rostral to
      the site of injury, thus offering insight into the potential anatomical
      reorganization and spinal plasticity following cervical contusion.

PMID- 21963674
TI  - Body image and cystic fibrosis: a critical review.
AB  - A slight frame and poor appetite are common among patients with cystic fibrosis
      (CF) yet healthy body weight has been related to a better prognosis. A review of
      studies exploring body image (BI) among adults and adolescents with CF was
      conducted. Seven electronic databases were searched for potential papers. They
      located 128 references, of which 24 were read in full and 12 included in the
      review. Accepted papers suggested females with CF had a better BI compared to
      males, but this could compromise survival, given their preference for a low body
      weight. Males may be more motivated to adhere to nutritional advice because they
      favor a larger form. Practitioners should broach the topic of BI at clinic
      appointments to ensure this does not have a detrimental impact on self
      management, although more research is required to guide professionals in this
      task.

PMID- 21963676
TI  - Prospects for controlling future pandemics of influenza.
AB  - Pandemic influenza remains one of the most serious threats to global public
      health and continued global vigilance to monitor emerging threats is crucial. Of
      the weapons available to control a pandemic, vaccination is potentially the most
      powerful, but there are currently serious limitations to timely availability of
      vaccine supply in an emergency. Many novel influenza vaccines are in development,
      some of which have the potential to deliver the massive quantities of vaccine
      that would be required in a pandemic in a short period of time. However, for the
      foreseeable future, it is likely that the principal vaccine that will be deployed
      in a pandemic will be an inactivated egg-derived vaccine of the kind that has
      been available for several decades. This review will focus on the practical
      hurdles that need to be surmounted to deliver large amounts of safe and effective
      pandemic vaccine to the general public. There needs to be a continued focus on
      improvement to the vaccine response system that will require close collaboration
      between influenza and vaccine experts, manufacturers, regulators and public
      health authorities around the world.

PMID- 21963677
TI  - Immune responses to influenza virus infection.
AB  - Influenza viruses cause annual outbreaks of respiratory tract infection with
      attack rates of 5-10%. This means that humans are infected repeatedly with
      intervals of, on average, 10-20 years. Upon each infection subjects develop
      innate and adaptive immune responses which aim at clearing the infection. Strain
      specific antibody responses are induced, which exert selective pressure on
      circulating influenza viruses and which drive antigenic drift of seasonal
      influenza viruses, especially in the hemagglutinin molecule. This antigenic drift
      necessitates updating of seasonal influenza vaccines regularly in order to match
      the circulating strains. Upon infection also virus-specific T cell responses are
      induced, including CD4+ T helper cells and CD8+ cytotoxic T cells. These cells
      are mainly directed to conserved proteins and therefore display cross-reactivity
      with a variety of influenza A viruses of different subtypes. T cell mediated
      immunity therefore may contribute to so-called heterosubtypic immunity and may
      afford protection against antigenically distinct, potentially pandemic influenza
      viruses. At present, novel viral targets are identified that may help to develop
      broad-protective vaccines. Here we review the various arms of the immune response
      to influenza virus infections and their viral targets and discuss the possibility
      of developing universal vaccines. The development of such novel vaccines would
      imply that also new immune correlates of protection need to be established in
      order to facilitate assessment of vaccine efficacy.

PMID- 21963678
TI  - A review of Nipah and Hendra viruses with an historical aside.
AB  - The emergence of Hendra and Nipah viruses in the 1990s has been followed by the
      further emergence of these viruses in the tropical Old World. The history and
      current knowledge of the disease, the viruses and their epidemiology is reviewed
      in this article. A historical aside summarizes the role that Dr. Brian W.J. Mahy
      played at critical junctures in the early stories of these viruses.

PMID- 21963679
TI  - Recombinant AexU effector protein of Aeromonas veronii bv. sobria disrupts the
      actin cytoskeleton by downregulation of Rac1 and induces direct cytotoxicity to
      beta4-integrin expressing cell lines.
AB  - AexU is a type three secretion system (TTSS) effector of Aeromonas hydrophila
      which has an in vitro ADP-ribosyltransferase (ART) and GTPase-activating protein
      (GAP) activities on Rac1, RhoA and Cdc42. Here we show that, AexU of Aeromonas
      veronii bv. sobria AeG1 strain disrupts actin cytoskeleton of HeLa cells during
      AeG1 infection, aexU transfection or direct application of AexU protein. Such
      cellular disruption was rescued by either inactivation of AexU-GAP activity by
      substitution of arginine residue 143 to alanine or expression of a constitutively
      active (CA) Rac1 but not CA RhoA or CA Cdc42. On the other hand, AexU was found
      co-localized with beta4-integrin probably through its Arg-Gly-Asp (RGD) integrin
      binding motif (319-321) residues. Interestingly, direct application of GST-AexU
      HA fusion protein caused significant cytotoxic effect on beta4-integrin
      expressing HT-29 cells. In contrast, beta4-integrin blockade with a specific
      antibody reduced such cytotoxicity. Consequently, AexU cytotoxic effect was
      exaggerated with a greater expression of beta4-integrin in Caco-2 and HeLa cells,
      while it was incompetent on beta4-integrin non-expressing CHO cells. As far as we
      know, this is a novel TTSS effector which specifically inactivates Rac1 to
      disrupt actin cytoskeleton and has an alternative cytotoxic pathway through beta4
      integrin mediation.

PMID- 21963680
TI  - Young adult African American patients with type 2 diabetes: a high risk patient
      sub-group with few supports for good diabetes management.
AB  - This study examined age differences in support, BMI, and HbA1c among African
      American patients with type 2 diabetes. Participants were 158 African American
      adults with type 2 diabetes. Average HbA1c was 1% higher among patients aged 20
      49 than patients 60-77, and double the number of younger patients had a BMI >=35
      than older patients. Younger patients reported less trust in their physician and
      greater disagreement with recommendations. They reported relying less on
      partners, greater unresolved conflict with partners around diabetes, and less
      church involvement. The association between age and HbA1c was partially mediated
      by patients' trust of their physician.

PMID- 21963681
TI  - Promoting positive motherhood among nulliparous pregnant women with an intense
      fear of childbirth: RCT intervention.
AB  - This RCT intervention among nulliparous pregnant women with an intense fear of
      childbirth sought to promote preparedness for childbirth and to enhance positive
      parenting. Pregnant women (n = 8,611) filled in a 'fear of childbirth'
      questionnaire. Nulliparous women with severe fear of childbirth (n = 355) were
      randomized into intervention (n = 131; 41 refused) and control (n = 224) groups.
      They rated themselves on a preparedness scale in middle and late pregnancy, and
      on a motherhood scale three months after childbirth. The intervention included
      six psycho-education group sessions during pregnancy and one after childbirth.
      This intervention increased the mothers' preparedness for childbirth, which
      predicted an increase in positive motherhood.

PMID- 21963682
TI  - Diagnostic profiles determined by the C.A.R.T procedure: IBD patients and
      fatigue.
AB  - Fatigue is common in IBD. It remains a complex phenomenon with primary factors
      related to the disease and secondary factors (depression, anxiety, sleep
      disturbances, pain) whose respective importance and organization are difficult to
      determine. By using the C.A.R.T. procedure, the diagnostic variables of 108 IBD
      related fatigue patients were determined globally, according to their sex and the
      clinical activity of their disease. Results underline the diversity of diagnostic
      profiles in which psychological variables have significant influence. It is
      important to consider fatigue according to profiles that best illustrate its
      complexity and allow for identifying better potentially remediable factors.

PMID- 21963683
TI  - Differences in the impact of the frequency and enjoyment of joint family
      activities on adolescent substance use and violence.
AB  - Previous research has concentrated exclusively on the association between the
      frequency of joint family activities (JFA) and adolescent problem behaviours. In
      this study, multiple linear regressions based on a national sample of 3467 13- to
      16-year-olds in Switzerland revealed that JFA enjoyment rather than JFA frequency
      is consistently related to low adolescent substance use and violence. By choosing
      JFA that their children enjoy, parents might provide opportunities for
      disclosure, strengthen family bonds and reduce the likelihood of adolescent
      problem behaviours. In terms of prevention, a shift in focus towards the quality
      rather than the quantity of JFA could prove more effective.

PMID- 21963684
TI  - Systems biology for biomedical innovation.

PMID- 21963675
TI  - Progress in understanding and controlling respiratory syncytial virus: still
      crazy after all these years.
AB  - Human respiratory syncytial virus (RSV) is a ubiquitous pathogen that infects
      everyone worldwide early in life and is a leading cause of severe lower
      respiratory tract disease in the pediatric population as well as in the elderly
      and in profoundly immunosuppressed individuals. RSV is an enveloped, nonsegmented
      negative-sense RNA virus that is classified in Family Paramyxoviridae and is one
      of its more complex members. Although the replicative cycle of RSV follows the
      general pattern of the Paramyxoviridae, it encodes additional proteins. Two of
      these (NS1 and NS2) inhibit the host type I and type III interferon (IFN)
      responses, among other functions, and another gene encodes two novel RNA
      synthesis factors (M2-1 and M2-2). The attachment (G) glycoprotein also exhibits
      unusual features, such as high sequence variability, extensive glycosylation,
      cytokine mimicry, and a shed form that helps the virus evade neutralizing
      antibodies. RSV is notable for being able to efficiently infect early in life,
      with the peak of hospitalization at 2-3 months of age. It also is notable for the
      ability to reinfect symptomatically throughout life without need for significant
      antigenic change, although immunity from prior infection reduces disease. It is
      widely thought that re-infection is due to an ability of RSV to inhibit or
      subvert the host immune response. Mechanisms of viral pathogenesis remain
      controversial. RSV is notable for a historic, tragic pediatric vaccine failure
      involving a formalin-inactivated virus preparation that was evaluated in the
      1960s and that was poorly protective and paradoxically primed for enhanced RSV
      disease. RSV also is notable for the development of a successful strategy for
      passive immunoprophylaxis of high-risk infants using RSV-neutralizing antibodies.
      Vaccines and new antiviral drugs are in pre-clinical and clinical development,
      but controlling RSV remains a formidable challenge.

PMID- 21963686
TI  - Comparative analysis of the molecular mechanisms controlling the initiation of
      chromosomal DNA replication in yeast and in mammalian cells.
AB  - In eukaryotes DNA replication takes place in the S phase of the cell cycle. It
      initiates from hundreds to thousands of replication origins in a coordinated
      manner, in order to efficiently duplicate the genome. The sequence of events
      leading to the onset of DNA replication is conventionally divided in two
      interdependent processes: licensing-a process during which replication origins
      acquire replication competence but are kept inactive- and firing-a process during
      which licensed origins are activated but not re-licensed. In this review we
      investigate the evolutionary conservation of the molecular machinery
      orchestrating DNA replication initiation both in yeast and in mammalian cells,
      highlighting a remarkable conservation of the general architecture of this
      central biological mechanism. Many steps are conserved down to molecular details
      and are performed by orthologous proteins with high sequence conservation, while
      differences in molecular structure of the performing proteins and their
      interactions are apparent in other steps. Tight regulation of initiation of DNA
      replication is achieved through protein phosphorylation, exerted mostly by Cyclin
      dependent kinases in order to ensure that each chromosome is fully replicated
      once, and only once, during each cycle, and to avoid the formation of aberrant
      DNA structures and incorrect chromosomal duplication, that in mammalian cells are
      a prerequisite for genome instability and tumorigenesis. We then consider a
      molecular mathematical model of DNA replication, recently proposed by our group
      in a collaborative project, as a frame of reference to discuss similarities and
      differences observed in the regulatory program controlling DNA replication
      initiation in yeast and in mammalian cells and discuss whether they may be
      dependent upon different functional constraints. We conclude that a systems
      biology approach, integrating molecular analysis with modeling and computational
      investigations, is the best choice to investigate the control of DNA replication
      in mammalian cells.

PMID- 21963685
TI  - The imminent role of protein engineering in synthetic biology.
AB  - Protein engineering has for decades been a powerful tool in biotechnology for
      generating vast numbers of useful enzymes for industrial applications. Today,
      protein engineering has a crucial role in advancing the emerging field of
      synthetic biology, where metabolic engineering efforts alone are insufficient to
      maximize the full potential of synthetic biology. This article reviews the
      advancements in protein engineering techniques for improving biocatalytic
      properties to optimize engineered pathways in host systems, which are
      instrumental to achieve high titer production of target molecules. We also
      discuss the specific means by which protein engineering has improved metabolic
      engineering efforts and provide our assessment on its potential to continue to
      advance biology engineering as a whole.

PMID- 21963687
TI  - Apo-10'-lycopenoic acid impacts adipose tissue biology via the retinoic acid
      receptors.
AB  - Apo-10'-lycopenoic acid (apo-10-lycac), a metabolite of lycopene, has been shown
      to possess potent biological activities, notably via the retinoic acid receptors
      (RAR). In the current study, its impact on adipose tissue and adipocytes was
      studied. In microarray experiments, the set of genes regulated by apo-10-lycac
      treatments was compared to the set of genes regulated by all-trans retinoic acid
      (ATRA), the natural ligand of RAR, in adipocytes. Approximately 27.5% of the
      genes regulated by apo-10-lycac treatments were also regulated by ATRA,
      suggesting a common ability in terms of gene expression modulation, possibly via
      RAR transactivation. The physiological impact of apo-10-lycac on adipose tissue
      biology was evaluated. If it had no effect on adipogenesis in the 3T3-L1 cell
      model, this metabolite may have a preventative effect against inflammation, by
      preventing the increase in the inflammatory markers, interleukin 6 and
      interleukin 1beta in various dedicated models. The ability of apo-10-lycac to
      transactivate the RAR and to modulate the transcription of RAR target gene was
      brought in vivo in adipose tissue. While apo-10-lycac was not detected in adipose
      tissue, a metabolite with a molecular weight with 2Da larger mass was detected,
      suggesting that a dihydro-apo-10'-lycopenoic acid, may be present in adipose
      tissue and that this compound could active or may lead to further active RAR
      activating apo-10-lycac metabolites. Since apo-10-lycac treatments induce anti
      inflammatory effects in adipose tissue but do not inhibit adipogenesis, we
      propose that apo-10-lycac treatments and its potential active metabolites in WAT
      may be considered for prevention strategies relevant for obesity-associated
      pathologies.

PMID- 21963689
TI  - Conceptual discord in psychiatry: origin, implications and failed attempts to
      resolve it.
AB  - Unlike other medical disciplines, psychiatry abounds in conceptual models. All of
      them are legitimate as there is no conclusive evidence that either is more proper
      than others in terms of its capacity to explicate the very nature of mental
      disorders and make possible more efficacious treatment of those with mental
      illness. There are two major sources of the existence of numerous models in
      psychiatry: difficulties in discerning the role played by the biological and the
      psychological in the genesis and treatment of individual mental disorders, and
      want of a widely accepted theory of the mind-body relationship. The conceptual
      divide in psychiatry has numerous negative effects: scarce communication or no
      communication between the advocates of different approaches; over-rating of the
      benefits of the concept one clings to; lack of interest in other approaches;
      confusion of clients when confronted with different explanation of the origin of
      their troubles and most appropriate treatment; tarnished image of psychiatry.
      There have been several attempts to correct conceptual cacophony in psychiatry.
      None of them proved successful.

PMID- 21963688
TI  - Oxidative DNA damage induced by iron chloride in the larvae of the lace coral
      Pocillopora damicornis.
AB  - Biochemical and molecular biomarkers tools are utilized as early warning
      signatures of contaminant exposure to target and non-target organisms. The
      objective of this study was to investigate the sublethal effects of iron chloride
      to the larvae of the lace coral Pocillopora damicornis by measuring a suit of
      oxidative-stress biomarkers. The larvae were exposed to a range of sublethal
      concentrations of iron chloride (0.01, 0.1, 1, 10, and 100 ppm) for seven days.
      With reference to oxidative stress biomarkers, the no-observed effect
      concentration (NOEC) and the lowest observed effect concentration (LOEC) of iron
      chloride were observed to be 0.01 and 100 ppm respectively. At the end of the
      seventh day the antioxidant status of the larvae was evaluated by the levels of
      glutathione (GSH), glutathione peroxidase (GPX), glutathione reductase (GR), and
      glutathione-S-transferase (GST), in both experimental and control groups. For the
      quantification of cellular oxidative damage, lipid peroxidation (LPO) activity
      was determined in the same and the extent of DNA damage was assessed by the
      expression of DNA apurinic/apyrimidinic (AP) sites. Iron chloride exhibited a
      concentration-dependent inhibition of GSH and GPX and induction of GR, GST, LPO,
      and DNA-AP sites in the P. damicornis larvae when compared to the control group.
      The oxidative stress biomarkers of the larvae exposed to 0.1, 1, and 10 ppm of
      iron chloride did not show any significant overall differences when compared to
      the control group. However the activities of LPO, GSH, GPX, GR, GST and DNA-AP in
      the larval group exposed to 100 ppm of iron chloride exhibited statistically
      significant (P=0.002, 0.003, 0.002, 0.002, 0.005 and 0.007) differences when
      compared to the control group. The research results indicated that iron chloride
      in concentrations at the 100 ppm level caused oxidative stress in the P.
      damicornis larvae.

PMID- 21963690
TI  - Oxidative stress in schizophrenia - focusing on the main markers.
AB  - Oxidative stress is the condition arising from imbalance between toxic reactive
      oxygen species and antioxidant systems. It is believed that increased oxidative
      stress may be relevant to the pathophysiology of schizophrenia. In this way, the
      main markers of the lipid peroxidation processes include 4-hydroxynonenal and
      malondialdehyde. On the other side, the potential toxicity of free radicals is
      counteracted by a number of cytoprotective antioxidant enzymes that limit the
      damage, such as superoxide dismutase and glutathione peroxidase. However, the
      reports regarding the status of oxidative stress markers schizophrenia are very
      inconsistent, with various authors stating both increased and decreased
      activities of the main antioxidant enzymes, while others did not observe any
      significant modifications, as compared to control groups. Similar aspects were
      also reported in the case of the lipid peroxidation markers, although in here the
      contradictions are much more reduced than in the case of the antioxidant
      defences. It is generally believed that the equivocal results mentioned above may
      be due to different tissues studies, different species or the administrated
      treatment and the duration of the disease/treatment. In this context, in the
      present paper we were interested to review some studies regarding the oxidative
      stress status in patients and animal models of schizophrenia, by referring mainly
      to antioxidant enzymes and lipid peroxidation markers.

PMID- 21963691
TI  - Person-centered medicine versus personalized medicine: is it just a sophism? A
      view from chronic pain management.
AB  - The main aim of this brief overview is to explore the concepts of person-centered
      medicine and personalized medicine in the areas of chronic pain research and
      management. Through several definitions and paradigms of pain, the authors
      introduce the complexity of pain phenomenology in order to establish the
      challenge of person-centered and personalized medicine in everyday practice. By
      providing deeper insight into fibromyalgia, its presentation, biology and
      treatment, several questions are addressed, ranging from person-centered
      diagnosis to personalizing the various processes of the fibromyalgia spectrum
      complex. By reviewing current treatment options and evaluating treatment pitfalls
      derived from methodological flaws in current research, the authors discuss
      various possibilities of personalizing treatment and, therefore, propose how the
      use of these two paradigms could enhance outcomes in chronic pain management.  If
      we wish to make comments about enhanced outcomes we need to talk about outcomes
      of pain treatments, we need to discuss what successful treatment is from the
      patient's point of view as well as in the reviewed models.

PMID- 21963692
TI  - The overlap of cognitive impairment in depression and schizophrenia: a
      comparative study.
AB  - BACKGROUND: Schizophrenia (SCH) is primarily a cognitive dysfunction. Its
      specific cognitive impairment profile was identified and suggestions have been
      made to include it in present diagnostic instruments as a special differential
      diagnostic criterion. However, studies indicate a substantial overlap of
      cognitive deficits between SCH patients and those with depression (DEP). In order
      to elucidate the structure of cognitive functioning in both entities, principal
      cognitive domains of SCH and DEP patients were assessed in the acute phase of
      disease. SUBJECTS AND METHODS: 44 SCH and 30 DEP patients, matched according to
      age, gender, education, IQ score, and duration of hospitalization were included.
      Neurocognitive assessments were performed in the first week of hospitalization
      using Digit Span test (working memory, attention), Trail Making Test (psychomotor
      speed, sustained attention, shifting), Rey's Complex Figure Test and Verbal
      Learning Test (perceptual organization, visual and verbal learning and memory).
      Results were evaluated according to demographically matched test norms. For
      statistics Student's t tests were used. RESULTS: In both study groups deficits in
      maintenance and shifting of attention during psychomotor tasks were found, while
      automatic processes (working memory, sustained attention) were preserved. In both
      groups memory and learning processes were impaired, in DEP however, deficits in
      attention shifting during cognitive tasks and delayed recall of visual material
      were more intense. CONCLUSIONS: In the acute phase of schizophrenia and
      depression similar cognitive impairment profiles can be found. Further studies
      are needed to assess longitudinal dynamics and possible later development of
      specific patterns of cognitive functioning in these patients.

PMID- 21963693
TI  - Tianeptine in the combined treatment of combat related posttraumatic stress
      disorder.
AB  - BACKGROUND: The aim of this study was to evaluate the efficacy of tianeptine, an
      antidepressant that acts by increasing serotonin reuptake, in the treatment of
      posttraumatic stress disorder and to compare the effects of tianeptine and
      fluoxetine, an antidepressant from the selective serotonin reuptake inhibitors
      class. SUBJECTS AND METHODS: 43 war veterans suffering from posttraumatic stress
      disorder were included in the study. During the 5.5 months of treatment 21
      patients were receiving tianeptine and 22 were receiving fluoxetine. In addition,
      all patients took part in intensive trauma specific group psychotherapy. The
      effects of the two antidepressants on symptoms of PTSD, depression and anxiety
      after 5.5 months of treatment were assessed using the Harvard Trauma
      Questionnaire, Beck Depression Inventory, STAI and the List of Drug Use and Side
      Effects. RESULTS: There was no significant difference between the two treatment
      groups regarding their effect on symptoms and severity of depression. The level
      of anxiety was the same in the first measurement but the difference became
      significant in other three measurements in favor of tianeptine. The anxiolytics
      and other co-prescribed drugs remain the same in both groups, the use of
      analgesics significantly increase in fluoxetine group during the course of
      treatment. CONCLUSION: The study demonstrated that tianeptine is as effective as
      fluoxetine in the treatment of PTSD, with even stronger effect on anxiety and
      equal tolerance.

PMID- 21963694
TI  - Anxiety in epileptic patients.
AB  - BACKGROUND: Anxiety may occur as ictal, postictal or interictal symptom in
      patients with epilepsy. The main aim of this research was to explore the
      intensity and frequency of anxiety in patients with generalized, temporal and
      extratemporal epilepsy. SUBJECTS AND METHODS: This is a cross-sectional study of
      three groups of patients with epilepsy (30 patients per group) - recently
      diagnosed with generalized epilepsy, temporal epilepsy and extratemporal
      epilepsy, and a healthy control group (N=30). The Beck Anxiety Inventory (BAI)
      was used for quantitative assessment of anxiety. RESULTS: Patients with temporal
      and extratemporal epilepsies had a significantly higher mean total scores on the
      BAI than the patients with generalized forms of epilepsies (ANOVA: F=6.323,
      p<0.01). There were no statistically significant differences between the temporal
      and extratemporal epilepsy groups according to the levels of anxiety on BAI (t
      test: t=1.68, p>0.05). For the first three symptoms - numbness, wobbling in the
      legs and the fear of the worst happening - the group of patients with
      extratemporal epilepsies had significantly higher average levels of intensity and
      frequency of symptoms (ANOVA: F1=5.591, F2=6.555, F3=5.906; p<0.01) CONCLUSIONS:
      Patients with partial epilepsy have more frequent and prominent anxiety symptoms
      than patients with generalized epilepsy, and also more than the control group.
      All these findings clearly indicate the necessity to modify treatment strategies
      accordingly in order to include both the antiepileptic therapy and treatment for
      anxiety disorders.

PMID- 21963695
TI  - Families and health interactions.
AB  - BACKGROUND: In recent years, psychologists of health have attempted to understand
      the relations between family dynamics and health. The aim of our study is not
      only to study relations inside families and couples (relations between family of
      origin, nuclear and ideal family, current and ideal couple) but also outside
      between families and couples and different health indicator (physical and mental
      health, consumption of medications, and frequency of medical consultations).
      SUBJECTS AND METHODS: Twenty healthy subjects are included in a two years long
      longitudinal study. At baseline, subjects' age, gender, family composition, net
      income, chronic treatments, family dynamics (FACES III), Health Locus of Control
      (MHLC), and personality (NEO-FFI) are recorded. RESULTS: The adaptability level
      that we experience in our current couple appears partially to be an inherited
      value of the adaptability that we had in our family of origin (r=0.694; p=0.026).
      Moreover, the closer we are to each other in our nuclear family, the closer and
      more adaptable is our couple (r=0.893; p=0.007). Cohesion in the nuclear family
      is correlated with a desire for even more cohesion in the ideal family (r=0.898;
      p=0.000) and in the ideal couple (r=0.732; p=0.016). The only mechanism that
      slows down this aspiration for "always more" cohesion is the cohesion that the
      current couple is experiencing. Some of these factors seem to affect health
      indicators: cohesion of the ideal family and of the family of origin as well as
      cohesion of the current couple have positive effects on health indicators whereas
      levels of adaptability of the ideal family and the current couple have negative
      effects on health indicators. CONCLUSION: At T0 and T6 months, the level of
      physical health appears to be the more predictable variable. At time T0, a tree
      factors model of linear regression including cohesion of family of origin, and of
      the current couple, with adaptability of the ideal family explains 82.4% of the
      variance. At time T6months, nuclear family cohesion, account for 46.5% of the
      variance.

PMID- 21963696
TI  - Pigro: an "absolute individualist" and his portrait studies.

PMID- 21963697
TI  - A rare case of male hysteria - hemiparesis successfully treated with
      amitriptyline.

PMID- 21963698
TI  - Psychodynamic psychopharmacotherapy and application of "brain-mind" concept.

PMID- 21963699
TI  - A critical account of the current approach to education in clinical
      psychopharmacology.

PMID- 21963700
TI  - New strategies in the treatment of bipolar disorder.

PMID- 21963701
TI  - Do we need new therapeutic strategies for depression?

PMID- 21963702
TI  - Antipsychotics as antidepressants: what is the mechanism?

PMID- 21963703
TI  - Etiology of schizophrenia and therapeutic options.

PMID- 21963704
TI  - Availability of new psychiatric medications, especially antipsychotics, in
      context of patient rights and destigmatization of psychiatric patients.

PMID- 21963705
TI  - Availability of psychiatric medications to Croatian healthcare users and the
      influence of availability of atypical antipsychotics on psychiatric hospital
      morbidity.

PMID- 21963706
TI  - Intersubjectivity and psychopharmacotherapy in the treatment of chronically
      suicidal patients.

PMID- 21963707
TI  - Review: interpersonal psychotherapy is effective as an acute or maintenance
      treatment for unipolar depression.

PMID- 21963708
TI  - Review: little evidence of clear benefit for most medical treatments for children
      with autism spectrum disorders.

PMID- 21963709
TI  - The Meds-Help pharmacy-based intervention increases antipsychotic drug adherence,
      but not symptoms.

PMID- 21963710
TI  - In people taking antidepressants, suicidal behaviour is less common when they are
      taking them than in unexposed periods.

PMID- 21963711
TI  - Review: possible benefits from early intensive behavioural and developmental
      interventions in children with autism spectrum disorders, but more research
      needed.

PMID- 21963712
TI  - Review: response to antipsychotics in schizophrenia in published trials of
      limited clinical significance.

PMID- 21963713
TI  - Siblings of adolescents with ADHD who themselves have ADHD are more likely to
      have psychiatric comorbidities than are unaffected siblings or controls without
      ADHD.

PMID- 21963714
TI  - Ambipolar field effect in the ternary topological insulator (Bi(x)Sb(1-x))2Te3 by
      composition tuning.
AB  - Topological insulators exhibit a bulk energy gap and spin-polarized surface
      states that lead to unique electronic properties, with potential applications in
      spintronics and quantum information processing. However, transport measurements
      have typically been dominated by residual bulk charge carriers originating from
      crystal defects or environmental doping, and these mask the contribution of
      surface carriers to charge transport in these materials. Controlling bulk
      carriers in current topological insulator materials, such as the binary
      sesquichalcogenides Bi2Te3, Sb2Te3 and Bi2Se3, has been explored extensively by
      means of material doping and electrical gating, but limited progress has been
      made to achieve nanostructures with low bulk conductivity for electronic device
      applications. Here we demonstrate that the ternary sesquichalcogenide (Bi(x)Sb(1
      x))2Te3 is a tunable topological insulator system. By tuning the ratio of bismuth
      to antimony, we are able to reduce the bulk carrier density by over two orders of
      magnitude, while maintaining the topological insulator properties. As a result,
      we observe a clear ambipolar gating effect in (Bi(x)Sb(1-x))2Te3 nanoplate field
      effect transistor devices, similar to that observed in graphene field-effect
      transistor devices. The manipulation of carrier type and density in topological
      insulator nanostructures demonstrated here paves the way for the implementation
      of topological insulators in nanoelectronics and spintronics.

PMID- 21963715
TI  - A decision-directed approach for prioritizing research into the impact of
      nanomaterials on the environment and human health.
AB  - The emergence of nanotechnology has coincided with an increased recognition of
      the need for new approaches to understand and manage the impact of emerging
      technologies on the environment and human health. Important elements in these new
      approaches include life-cycle thinking, public participation and adaptive
      management of the risks associated with emerging technologies and new materials.
      However, there is a clear need to develop a framework for linking research on the
      risks associated with nanotechnology to the decision-making needs of
      manufacturers, regulators, consumers and other stakeholder groups. Given the very
      high uncertainties associated with nanomaterials and their impact on the
      environment and human health, research resources should be directed towards
      creating the knowledge that is most meaningful to these groups. Here, we present
      a model (based on multi-criteria decision analysis and a value of information
      approach) for prioritizing research strategies in a way that is responsive to the
      recommendations of recent reports on the management of the risk and impact of
      nanomaterials on the environment and human health.

PMID- 21963716
TI  - Cell signaling in regulation of the barrier integrity of the corneal endothelium.
AB  - The barrier integrity of the corneal endothelium, which is conferred by its tight
      and adherens junctions, is critical for the maintenance of deturgescence of the
      corneal stroma. Although characteristically leaky, the barrier integrity
      restricts fluid leakage into the stroma such that the rate of leak does not
      exceed the rate of the endothelial active fluid transport directed toward the
      aqueous humor. At a molecular level, the barrier integrity is influenced by the
      actin cytoskeleton and microtubules, which are coupled to tight and adherens
      junctions via a variety of linker proteins. Since the cytoskeleton is affected by
      Rho family small GTPases and p38 MAP kinase, among others, many
      pathophysiological stimuli induce plasticity to the cytoskeleton and thereby
      elicit dynamic regulation of the barrier integrity. This review presents an
      overview of the impact of several bioactive factors on the barrier integrity of
      the corneal endothelium through altered actin cytoskeleton and/or disassembly of
      microtubules. The main focus is on the effect of TNF-alpha (tumor necrosis factor
      alpha) which is a pro-inflammatory molecule found in the intraocular milieu
      during allograft rejection and anterior uveitis. This cytokine elicits acute
      activation of p38 MAP kinase, induces disassembly of microtubules, disrupts the
      peri-junctional actomyosin ring, and concomitantly breaks down the barrier
      integrity. These effects of TNF-alpha could be inhibited by stabilizing the
      microtubules, co-treating with a selective p38 MAP kinase inhibitor, and
      elevating intracellular cAMP via A2B receptors or direct exposure to forskolin.
      Overall, the corneal edema following a potential breakdown of the endothelial
      barrier integrity can be rescued pharmacologically by inhibiting specific cell
      signaling mechanisms.

PMID- 21963717
TI  - Accuracy and resolution of in vitro imaging based porcine lens volumetric
      measurements.
AB  - There is considerable interest in determining lens volume in the living eye. Lens
      volume is of interest to understand accommodative changes in the lens and to size
      accommodative IOLs (A-IOLs) to fit the capsular bag. Some studies have suggested
      lens volume change during accommodation. Magnetic Resonance Imaging (MRI) is the
      only method available to determine lens volume in vivo. MRI is, by its nature,
      relatively low in temporal and spatial resolution. Therefore analysis often
      requires determining lens volume from single image slices with relatively low
      resolution on which only simple image analysis methods can be used and without
      repeated measures. In this study, 7 T MRI scans encompassing the full lens volume
      were performed on 19 enucleated pig eyes. The eyes were then dissected to isolate
      and photograph the lens in profile and the lens volumes were measured empirically
      using a fluid displacement method. Lens volumes were calculated from two- and
      three-dimensional (2D and 3D) MR and 2D photographic profile images of the
      isolated lenses using several different analysis methods. Image based and actual
      measured lens volumes were compared. The average image-based volume of all lenses
      varied from the average measured volume of all lenses by 0.6%-6.4% depending on
      the image analysis method. Image analysis methods that use gradient based edge
      detection showed higher precision with actual volumes (r(2): 0.957-0.990), while
      threshold based segmentation had poorer correlations (r(2): 0.759-0.828). The
      root-mean-square (RMS) difference between image analysis based volumes and fluid
      displacement measured volumes ranged from 8.51 MUl to 25.79 MUl. This provides an
      estimate of the error of previously published methods used to calculate lens
      volume. Immobilized, enucleated porcine eyes permit improved MR image resolution
      relative to living eyes and therefore improved image analysis methods to
      calculate lens volume. The results show that some of the accommodative changes in
      lens volume reported in the literature are likely below the resolution limits of
      imaging methods used. MRI, even with detailed image analysis methods used here,
      is unlikely to achieve the resolution required to accurately size an A-IOL to the
      capsular bag.

PMID- 21963718
TI  - Thioredoxin stimulates MMP-9 expression, de-regulates the MMP-9/TIMP-1
      equilibrium and promotes MMP-9 dependent invasion in human MDA-MB-231 breast
      cancer cells.
AB  - Increased expression of thioredoxin (Trx)-1 and matrix metalloproteinase (MMP)-9
      associates with malignant breast cancer progression. Here, we describe a
      functional relationship between Trx-1 and MMP-9 in promoting MDA-MB-231 breast
      cancer cell invasive behaviour. Trx-1 overexpression stimulated MMP-9 expression,
      de-regulated the MMP-9/TIMP-1 equilibrium and augmented MMP-9 involvement in a
      more invasive phenotype. Trx-1 augmented MMP-9 transcription through NF-kappaB,
      AP-1 and SP1 elements; stimulated p50/p65 NF-kappaB activity and recruitment to
      the MMP-9 promoter; and facilitated MMP-9 promoter-accessibility to NF-kappaB by
      preventing HDAC recruitment and maintaining MMP-9 promoter histone acetylation.
      Our data provide a functional basis for Trx-1 and MMP-9 association in malignant
      breast cancer and identify Trx-1 and NF-kappaB as potentially druggable targets
      for reducing MMP-9 involvement in malignant behaviour.

PMID- 21963719
TI  - Iron influences the abundance of the iron regulatory protein Cir1 in the fungal
      pathogen Cryptococcus neoformans.
AB  - The GATA-type, zinc-finger protein Cir1 regulates iron uptake, iron homeostasis
      and virulence factor expression in the fungal pathogen Cryptococcus neoformans.
      The mechanisms by which Cir1 senses iron availability, although as yet undefined,
      are important for understanding the proliferation of the fungus in mammalian
      hosts. We investigated the influence of iron availability on Cir1 and found that
      the abundance of the protein decreases upon iron deprivation. This
      destabilization was influenced by reducing conditions and by inhibition of
      proteasome function. The combined data suggest a post-translational mechanism for
      the control of Cir1 abundance in response to iron and redox status.

PMID- 21963720
TI  - Identification of a unique splicing regulatory cluster in hepatitis B virus
      pregenomic RNA.
AB  - HBV particles with genome derived from spliced mRNAs accumulate in patients with
      virus-derived severe liver necrosis and fibrosis. We investigated the role of an
      intronic element (intronic splicing silencer-long, ISS(L)) on splicing of HBV
      minigene transcripts. Removal of the entire ISS(L) showed two-fold increase in
      splicing while shorter deletions within ISS(L) indicated isolated clusters of
      activator and repressor domains. Activator domains stimulated splicing in
      presence of PRE, a long HBV 3' exon and even when present in a heterologous
      context. Mutations in the repressor domain unexpectedly augmented repression. The
      role of this intronic splicing regulatory element could be important for HBV
      pathogenesis.

PMID- 21963721
TI  - Evaluation of group counseling for women with breast cancer in Turkey.
AB  - BACKGROUND: Breast cancer is one of the most commonly diagnosed cancers among
      women. Health services for breast cancer patients should give high priority to
      the social and psychological realities experienced by those dealing with the
      ramifications of their illness. Psychosocial interventions and group counseling
      for patients have been shown to be highly effective in the care of breast cancer
      patients. OBJECTIVE: This study was conducted to determine the effects of group
      counseling on the adaptation of breast cancer patients to their illness. METHOD:
      : Sessions are made weekly, and each session lasted about 1.5 to 2 hours, and the
      researchers attended all sessions together. Pretests were administered to the
      patients at the first of the 10 group sessions, and posttests were administered
      at the last group session. Pretest/posttest pattern data were collected from 56
      breast cancer patients using the Ways of Coping Inventory, the Psychosocial
      Adjustment to Illness Scale-Self-report, and the Multidimensional Scale of
      Perceived Social Support. These were evaluated using the SPSS 9.0 statistical
      package. RESULTS: After group counseling, patients showed an increase in their
      positive perceptions of social support, psychosocial adaptation, and in their
      abilities to cope with breast cancer. CONCLUSIONS: : The findings indicate that
      this group-counseling program positively affected patients' perceived social
      support and enhanced their abilities to effectively cope with stress.
      IMPLICATIONS FOR PRACTICE: Cancer patients can have various problems in the
      adaptation process to cancer. Therefore, oncology nurses should be actively
      involved in working with patients to find solutions and ways of coping with the
      issues they face.

PMID- 21963722
TI  - Breast and cervical cancer screening among South Asian immigrants in the United
      States.
AB  - BACKGROUND: South Asian (SA) immigrants (from Bangladesh, Bhutan, India, the
      Maldives, Nepal, Pakistan, and Sri Lanka) constitute the fastest growing of all
      Asian American immigrants to the United States, with a growth rate of 106% from
      1990 to 2001. Data are lacking on health behaviors of this population subgroup,
      including cancer-related information. OBJECTIVE: : The purpose of this study was
      to assess rates and correlates of breast and cervical cancer screening in a
      community sample of SAs. METHODS: Participants were recruited from among
      attendees of 3 community-based agency programs. Data were collected in English,
      Hindi, and Gujarati from a convenience sample of 198 participants. RESULTS: Two
      thirds of the sample (n = 127, 65.5%) had ever had a mammogram, whereas only a
      third (n = 65, 32.8%) had ever had a Papanicolaou smear or vaginal examination.
      Several predisposing factors (eg, country of birth, years in the United States,
      acculturation, age, and acknowledged barriers to screening) were significant
      predictors of breast and cervical screening, whereas the only enabling factor was
      past screening behavior. CONCLUSIONS: Additional study is warranted on cultural
      aspects of cancer screening behaviors. These data are formative on facilitators
      and barriers to mammogram and Papanicolaou test completion among these
      understudied minority women. IMPLICATIONS FOR PRACTICE: Nurses who practice in
      primary care may begin to target health education based on sociodemographics of
      SA women and emphasize discussion of barriers to screening.

PMID- 21963723
TI  - Efficacy and safety of combination therapy of natural human interferon beta and
      ribavirin in chronic hepatitis C patients.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of
      combination therapy of natural human interferon-beta and ribavirin for patients
      for whom prior interferon therapy was discontinued due to depression induced by
      interferon-alpha. METHODS: Inclusion criteria were as follows; 1) HCV-genotype
      1b, 2) serum HCV RNA level of >=100 KIU/mL, 3) stopping the prior interferon
      alpha monotherapy or combination therapy of interferon-alpha and ribavirin due to
      the appearance of depression. A total of 14 were enrolled in this prospective
      cohort study. The treatment period of combination therapy was 48 weeks.
      Depression states, reflected by Beck depression inventories and Hamilton
      depression rating scale, were assessed during combination therapy. Nonparametric
      procedures were employed for the analysis of background features of the patients
      with sustained virological response (SVR) and without SVR. A p value of <0.05 was
      considered to indicate a significant difference. RESULTS: Five of 14 patients
      (37.5%) had SVR by the intention to treat analysis. The SVR rate in patients who
      showed negative HCV RNA at 12 and 24 weeks after the initiation of combination
      therapy was 100% (4/4) and 83.3% (5/6), respectively. All of the patients
      continued the combination therapy owing to disappearance of severely adverse
      events contained the exacerbation of depression. Combination therapy did not
      yield a statistical difference in Beck depression inventories and Hamilton
      depression rating scale. CONCLUSION: The combination therapy of IFN-beta and
      ribavirin is a possible therapy selection for the patients for whom interferon
      therapy was discontinued due to depression induced by interferon-alpha.

PMID- 21963724
TI  - One-step placement of a fully-covered metal stent in endosonography-guided
      biliary drainage for malignant biliary obstruction.
AB  - BACKGROUND: Although reports on endosonography-guided biliary drainage (ESBD)
      have been increasing, only a few discuss deployment of a self-expandable metal
      stent (SEMS) in the first session. OBJECTIVE: To evaluate the safety and efficacy
      of ESBD with the one-step placement of a newly designed fully-covered SEMS.
      PATIENT AND METHODS: Five patients with malignant biliary obstruction in whom one
      step placement of an anti-migration designed SEMS in the first session of ESBD
      had been attempted between January 2007 and October 2009 were included in this
      study. Main outcome measurements were technical and clinical successes, early
      complications, and short-term results. RESULTS: ESBD was attempted to bridge the
      extrahepatic bile duct and the duodenum and one-step SEMS placement was
      successful in all cases. There were no early complications related to ESBD and
      excellent biliary decompression was obtained in all cases. SEMS dysfunction such
      as stent migration and occlusion was not seen during the follow-up period (mean
      follow-up 138 days, range 102-184 days). CONCLUSION: One-step placement of a
      fully-covered SEMS in ESBD is possibly a safe and effective treatment for biliary
      obstruction.

PMID- 21963725
TI  - Fever after percutaneous endovascular stent-graft in type B acute aortic
      dissection.
AB  - BACKGROUND AND PURPOSE: Fever is a common symptom of acute aortic dissection. The
      beginning time and duration of fever after percutaneous endovascular stent-graft
      in patients with aortic dissection is not well known. The present study was
      undertaken to investigate the characteristics of fever after percutaneous
      endovascular stent-graft in patients with type B aortic dissection. METHODS AND
      RESULTS: In this retrospective study the data of a total of 64 patients with type
      B acute aortic dissection undergoing percutaneous endovascular stent-graft were
      collected and analyzed. In total, 55 patients (85.9%) had fever after stent
      graft. The time of fever onset was during the initial 2 days after interventional
      procedure (92.7%), and the duration of fever of most patients was not beyond 7
      days after stent implantation. The fever before stent implantation was associated
      with the beginning time of fever after stent implantation, but not with the
      duration of fever. CONCLUSION: The results of this study could provide important
      reference information for the evaluation of fever before and after interventional
      treatment in patients with acute aortic dissection.

PMID- 21963726
TI  - Endothelial nitric oxide synthase G894T gene polymorphism and essential
      hypertension in the Chinese population: a meta-analysis involving 11,248
      subjects.
AB  - BACKGROUND: The endothelial nitric oxide synthase (eNOS) G894T gene polymorphism
      has been suggested to be linked to the risk of essential hypertension (EH),
      however the results are still debatable. OBJECTIVE AND METHODS: To assess the
      association between eNOS G894T gene polymorphism and EH, such electronic
      databases as Pubmed, Embase, Web of Science, China Biological Medicine Database
      (CBMD) and China National Knowledge Infrastructure (CNKI) were searched. The
      selection criteria were as follows: a) Evaluation of the association of eNOS
      G894T gene polymorphism and EH. b) EH diagnosis in compliance with EH diagnosis
      criteria of the World Health Organization (WHO) in 1999. c) The study results
      were in line with the Hardy-Weinberg equilibrium (HWE). In 23 separate studies
      with 11,248 subjects the relation between eNOS G894T gene polymorphism and EH was
      analyzed by current meta-analysis. Random effect model was used to calculate the
      pooled odds ratio (ORs) and its corresponding 95% confidence interval (95% CI).
      RESULTS: In this eNOS G894T gene polymorphism and EH meta-analysis in the Chinese
      population, the distribution of T allele frequency was 0.154 for EH group and
      0.128 for the control group. A significant association was found between G894T
      gene polymorphism and EH (p=0.0007). The pooled OR for the distribution frequency
      of T allele was 1.33 (95% CI:1.13-1.56, P(heterogeneity) <0.00001). In the
      stratified analysis by ethnicity, there was a significant association in Han
      subgroup (p=0.005). The pooled OR for the distribution frequency of T allele was
      1.31 (95% CI:1.09-1.59, P(heterogeneity) <0.00001). No significant increased risk
      for EH was found in the non-Han subgroup (p=0.08). CONCLUSION: In the current
      meta-analysis, T allele of eNOS G894T gene was suggested to be related to the
      increased risk of EH in the Chinese population, particularly in those of Han
      ethnicity.

PMID- 21963727
TI  - Relationship between blood pressure control status and lifestyle in hypertensive
      outpatients.
AB  - OBJECTIVE: Lifestyle modification as well as combination antihypertensive therapy
      is necessary to achieve strict blood pressure (BP) control as advocated by the
      guidelines for the treatment of hypertension. The aim of this study was to
      investigate the status of adherence to lifestyle modifications and BP control
      status in hypertensive outpatients. METHODS AND PATIENTS: Subjects are 661
      hypertensive outpatients who had been followed at National Kyushu Medical Center.
      We assessed BP control status based on the average clinic BP on two occasions. In
      addition, we investigated the adherence to the individual items of lifestyle
      modification by a questionnaire. RESULTS: Average BP was 129 +/- 10/71 +/- 11
      mmHg and overall rate of achieving goal BP was 60.1%. Achieving rate of each
      target BP category was 83.3% in the elderly patients (<140/90 mmHg), 56.7% in the
      young/middle patients (<130/85 mmHg) and 45.5% in the patients with diabetes
      mellitus/chronic kidney disease/myocardial infarction (<130/80 mmHg). Adherance
      to each item of lifestyle modification was as follows: Patients who answered to
      be conscious about salt restriction was 80.9%, those with increased intake of
      fruits/vegetables was 79.0%, reduced intake of cholesterol/saturated fatty acids
      was 67.9%, presence of obesity was 37.7%, daily exercise for >=30 min was 31.9%,
      habitual alcohol intake was 38.0%, habitual smoking was 9.8%. Only 22.5% of the
      patients had no lifestyle items to be modified. On the other hand, 19.6% of
      patients had more than 3 items to be modified. Subjects with more than 3
      lifestyle items to be modified are more frequently found in young, male, and
      obese groups. CONCLUSION: We conclude that about 60% of the patients achieved
      goal BP by the intensive combination therapy. The lifestyle modification seems to
      be important especially for the young, male and obese patients.

PMID- 21963728
TI  - Significance of high HDL cholesterol levels in Japanese men with metabolic
      syndrome.
AB  - OBJECTIVE: The objective was to clarify the significance of high high-density
      lipoprotein cholesterol (HDL-C) levels in the metabolic syndrome (MetS). The
      evaluation focused on insulin resistance as an indicator of early-stage MetS.
      METHODS AND SUBJECTS: Of 2705 men who first underwent an annual health check-up
      at Tokai University Hachioji Hospital, 2129 men were included in this study,
      after exclusion of those on medication for hypertension, diabetes or
      dyslipidemia, and those with a prior history of ischemic heart disease,
      cerebrovascular disease or chronic renal failure. MetS risk factors include the
      following five parameters: waist circumference, blood pressure, plasma glucose,
      triglycerides and HDL-C. The correlations between HDL-C and number of MetS risks
      with homeostasis model assessment of insulin resistance (HOMA-IR) were analyzed.
      HOMA-IR, number of risks, habits of smoking, exercise and drinking alcohol,
      stratified by HDL-C levels, were compared in MetS subjects. RESULTS: In cases
      with <=2 risk factors, the higher the HDL-C, the lower the HOMA-IR. However, with
      >=3 risk factors for MetS, the HOMA-IR increased when HDL-C was >=90 mg/dL. In
      MetS subjects, the rate of alcohol intake >=75 g/day was high when HDL-C was >=90
      mg/dL. CONCLUSION: In MetS subjects with high HDL-C levels, insulin resistance
      was increased. Therefore, in persons with high HDL-C levels, it is important to
      monitor the amount of alcohol consumption and reduce alcohol consumption to <75
      g/day.

PMID- 21963729
TI  - Influence of physical activity intensity and aerobic fitness on the
      anthropometric index and serum uric acid concentration in people with obesity.
AB  - BACKGROUND AND OBJECTIVE: Physical activity (PA) is considered an important
      approach to prevent and treat obesity and hyperuricemia. The purpose of the
      present study was to examine the influence of PA intensity and aerobic fitness on
      anthropometric indices and serum uric acid in obese individuals. METHODS: PA was
      examined using a single-axial accelerometer and aerobic fitness was assessed by
      electric cycle ergometry in obese middle-aged men (n=71, 47.2 +/- 4.4 years). PA
      was defined as light (<3 metabolic equivalents [METs]), moderate (3.0-6.0 METs)
      or vigorous (>6.0 METs) intensity from the corresponding METs multiplied by time
      spent at the corresponding intensity levels. Serum uric acid was measured by the
      uricase peroxidase method. RESULTS: The association between aerobic fitness index
      (lactate threshold) and serum uric acid did not reach statistical significance
      after adjustment for potential confounding factors (age, body mass index [BMI],
      and alcohol consumption) (beta=-0.110, p=0.138). Light intensity PA was inversely
      associated with BMI and waist circumference, even after adjustment for age and
      alcohol consumption (BMI: beta=-0.543, p=0.023; waist circumference: beta=-1.333,
      p=0.016). Moderate intensity PA, but not light or vigorous intensity PA, was
      inversely correlated with the uric acid level and this remained significant after
      adjustment for age, BMI, and alcohol consumption (beta=-0.222, p=0.036).
      CONCLUSION: Our results suggest that light intensity PA may have an important
      role in weight control while moderate intensity PA may be associated with the
      lower uric acid concentrations in obese individuals.

PMID- 21963731
TI  - Concerns with the health check-up system for chronic obstructive pulmonary
      disease on two Japanese islands.
AB  - OBJECTIVE: Early diagnosis is a key factor in the management of chronic
      obstructive pulmonary disease (COPD). Although mass screening is widely used,
      little is known about its accuracy and efficacy. This study investigated whether
      using spirometry during mass screening to detect COPD among community residents
      might be ineffective because of variability in the training and experience of
      examiners. PARTICIPANTS AND METHODS: Both spirometry and a self-written
      questionnaire-based survey, including questions designed to detect respiratory
      symptoms, were conducted on community residents. Two separate studies were
      conducted on islanders living in similar environments. Study I was performed from
      2004 to 2007 on Hachijyo Island residents, while study II, with a similar study
      design, was performed in 2003 on Inno Island residents. RESULTS: In study I,
      3,592 subjects underwent examination over the 4-year study period; of these, 378
      subjects underwent repeated examinations. Approximately 25% of the subjects had
      respiratory symptoms. Acceptable spirometry recordings were obtained for 62.0%
      (2004) to 84.1% (2006) of the subjects. In study II, 167 of the 254 subjects
      (65.7%) had respiratory symptoms. Acceptable assessment recordings were achieved
      in 254 subjects (95.5%). The suitability of the recordings was influenced by the
      extent/level of training of the examiners and the accompanying thoracic
      specialists. CONCLUSION: We concluded that the effectiveness of health check-ups
      for COPD evaluation using spirometry was greatly influenced by the quality of the
      examiners, even when the subjects had respiratory symptoms. Thus, we recommend
      caution when screening for early signs of COPD during health check-ups.

PMID- 21963730
TI  - Mechanisms of genistein protection on pancreas cell damage in high glucose
      condition.
AB  - AIM: An adequate beta cell number is important to prevent the onset and
      development of type 2 diabetes. The aim of this study was to determine if
      phytoestrogen gesintein has protective effects against high glucose-induced cell
      apoptosis in human pancreas cells, and to try to determine the possible mechanism
      for this protection. METHODS: Human pancreatic beta cells were subjected to
      normal (5 mM) or high glucose (25 mM) with and without the presence of 100 nM
      genistein, and also in the presence and absence of the pure anti-estrogen ICI
      182780 (100 nM). Bcl-2 siRNA transfection was performed to investigate if the
      effect of genistein was also Bcl-2 dependent. Cell proliferation and apoptosis
      were determined by Tritiated Thymidine Incorporation Assay and Cell Apoptosis
      Detection ELISA. Estrogen receptor and Bcl-2 mRNA expression was measured by Real
      time Quantitative PCR. RESULTS: High glucose concentration caused cell
      proliferation inhibition and apoptosis in cultured human pancreatic beta cells,
      and these effects were significantly reversed by genistein (P<0.01). Estrogen
      receptor beta was expressed in the cultured cells, and genistein protection was
      blocked by ICI-182780 administration as well as Bcl-2 siRNA transfection.
      CONCLUSION: Phytoestrogen gave protection against high glucose-induced pancreatic
      cell damage through estrogen receptor beta and Bcl-2 dependent pathways.

PMID- 21963732
TI  - CT-guided ultrathin bronchoscopy: bioptic approach and factors in predicting
      diagnosis.
AB  - BACKGROUND: The diagnostic sensitivity of current bronchoscopy for peripheral
      lung cancer is inadequate because the bronchoscope insertion range is limited and
      confirmation of the position of the biopsy apparatus at the lesion under X-ray
      fluoroscopy is inaccurate. The combination of ultrathin bronchoscopy and computed
      tomography (CT) is effective for solving these problems. OBJECTIVE: This study
      was a retrospective study analyzing prospectively collected data to identify
      factors contributing to the diagnosis and the appropriate biopsy method in CT
      guided ultrathin bronchoscopy for peripheral lung cancer. METHODS: The subjects
      comprised 86 patients (88 lesions) who underwent CT-guided ultrathin bronchoscopy
      and were finally diagnosed with peripheral lung cancer. We evaluated the
      diagnostic yield according to specific factors and also according to the sample
      collection method. RESULTS: Sixty-nine lesions were diagnosed as lung cancer, and
      the diagnostic yield was 78.4% (80.3% in lesions <=2 cm in diameter).
      Multivariate analysis showed that the factors contributing to the diagnosis were
      the observation range by ultrathin bronchoscopy and the presence/absence of the
      involved bronchus or pulmonary artery. Pathological evaluation facilitated
      histological diagnoses in 53 (65.4%) of 81 lesions. In 16 lesions, only the
      cytological diagnosis was positive. CONCLUSION: CT-guided ultrathin bronchoscopy
      may be particularly useful for lesions for which the involved bronchus or
      pulmonary artery can be confirmed, and observation of bronchi of the 6th
      generation or more is possible. Since the specimen preparation rate is low, the
      combination of histopathological diagnosis with cytological diagnosis
      particularly that of the discharge attached to the forceps, is optimal.

PMID- 21963733
TI  - Diagnostic value of serum procalcitonin and C-reactive protein for infections
      after allogeneic hematopoietic stem cell transplantation versus nontransplant
      setting.
AB  - OBJECTIVE: Procalcitonin (PCT) has been increasingly used as a biomarker of
      infection. The purpose of this study was to evaluate its diagnostic value after
      hematopoietic stem cell transplantation (HSCT), where non-infectious febrile
      complications such as graft-versus-host disease frequently develop. METHODS: We
      retrospectively analyzed 144 febrile episodes (infections: 82, and noninfections:
      62) in adult patients with hematological disorders, including 57 and 87 episodes
      in HSCT and non-HSCT patients, respectively. RESULTS: Of 57 febrile episodes in
      HSCT patients, 46 (86%) and 25 (44%) revealed positivity for C-reactive protein
      (CRP) and PCT, respectively. Among 87 febrile episodes in non-HSCT patients, 81
      (93%) and 22 (25%) events showed positive results of CRP and PCT. Both of these
      biomarkers were associated with infectious episodes in univariate analysis.
      Multivariate analysis showed that a high cut-off level (>9.5 mg/dL) of CRP was a
      better indicator for infections than PCT in HSCT patients, while PCT positivity
      was more diagnostic for infections than any cutoff CRP level in non-HSCT
      patients. CONCLUSION: It may be necessary to interpret the results of these
      biomarkers with different orders of priority in transplant versus nontransplant
      patients.

PMID- 21963734
TI  - Ultrasonography of carpal tunnel syndrome: clinical significance and limitations
      in elderly patients.
AB  - OBJECTIVE: Carpal tunnel syndrome (CTS) severity increases with age.
      Ultrasonographic measurement of the median nerve cross-sectional area (CSA) is an
      additional or complementary method for CTS diagnosis. The present study was aimed
      to investigate the diagnostic significance of median nerve CSA in various age
      groups of CTS patients. METHODS: The subjects were patients with
      electrophysiologically confirmed CTS and age-matched controls. Sonographic
      measurements of the median nerve CSA were performed. RESULTS: A total of 279
      hands of 175 patients with CTS and 50 normal hands were examined. CSA was
      correlated with distal motor and sensory latencies of the median nerve and
      severity of CTS. CTS severity increased with age, particularly in patients over
      80; however, their median nerve CSA was not enlarged regardless of their high
      severity of CTS. CONCLUSION: Although the median nerve CSA is a useful diagnostic
      measurement for CTS, it should be emphasized that its diagnostic significance
      might be limited in aged patients. In particular, in very elderly patients,
      careful evaluation of CTS severity is necessary.

PMID- 21963735
TI  - Pramipexole reduces the prevalence of fatigue in patients with Parkinson's
      disease.
AB  - OBJECTIVE: The aim of this multicenter cross-sectional study was to assess the
      relation between fatigue in a large number of Japanese patients with Parkinson's
      disease (PD) and drugs taken to treat PD. METHOD: We used the 16-item Parkinson
      Fatigue Scale (PFS-16), which was designed to assess fatigue exclusively
      associated with PD. Multiple logistic regression analyses were used to assess the
      relation between antiparkinson drugs and fatigue in PD. RESULTS: A total of 350
      non-demented PD patients were enrolled. Fatigue (PFS score of >=4) was revealed
      in 319 patients (91%). Pramipexole was administered to 24% of PD patients.
      Multiple logistic regression analysis revealed that the administration of
      Pramipexole was significantly related to low rates of fatigue in PD patients with
      Hoehn and Yahr stage <3 (p=0.011, odds ratio=5.23, 95% confidence interval; 1.47
      18.63). CONCLUSION: The reduced fatigue in PD patients was observed in taking
      Pramipexole.

PMID- 21963737
TI  - Thrombo-embolic renal infarction in a case of mid-ventricular takotsubo syndrome.
AB  - Thrombo-embolism is one of the serious complications of takotsubo syndrome (TS).
      It typically occurs in the classical mid-apical left ventricular ballooning form
      of TS. This complication has not been reported in cases of left mid-ventricular
      ballooning type of TS. We describe a 67-year-old woman who presented with 2-3
      days of increasing signs and symptoms of heart failure. Echocardiography showed
      marked hypokinesia/akinesia in the mid-anterior, mid-anterolateral, and mid
      inferior wall of the left ventricle and mild hypokinesia in the apical region.
      There was also hypokinesia of the mid and apical parts of the right ventricle.
      One day after admission, she developed acute left-sided renal infarction. Left
      ventriculography and coronary angiography 3 days after admission showed typical
      left mid-ventricular ballooning with no identifiable coronary lesion. Follow-up
      echocardiography showed complete resolution of left and right ventricular
      dysfunction. Takotsubo syndrome with right ventricular involvement complicated
      with heart failure and left renal embolic infarction was diagnosed. The mechanism
      of left renal embolic infarction is discussed.

PMID- 21963736
TI  - Severe hyponatremia in association with I(131) therapy in a patient with
      metastatic thyroid cancer.
AB  - Hyponatremia is a common clinical problem that results from various causes.
      Hypothyroidism is known to be one of the causes of this disorder. We report a
      case of metastatic thyroid cancer presenting with severe hyponatremia in
      association with hypothyroidism induced by pretreatment of I(131) therapy, such
      as a low-iodine diet and withdrawal of thyroid hormone. Serum arginine
      vasopressin (AVP) was elevated and urine osmolality was higher than that of
      serum. Saline infusion and thyroid hormone replacement normalized serum sodium
      and AVP. Inappropriate secretion of AVP in hypothyroid state was thought to be
      one of the causes of this hyponatremia.

PMID- 21963738
TI  - A 27-year-old woman diagnosed as polycystic ovary syndrome associated with
      Graves' disease.
AB  - Polycystic ovary syndrome (PCOS) and Graves' disease are the common causes of
      menstrual irregularity leading to infertility in women of child-bearing age. A 21
      year-old female patient visited us with complaints of oligomenorrhea and hand
      tremor. She was diagnosed as having PCOS and hyperthyroid Graves' disease,
      simultaneously. She had low body weight (BMI: 16.4 kg/m(2)), mild hirsutism, and
      thyrotoxicosis. The patient was treated with anti-thyroid drug and beta-blocker
      for about two years, and then recovered to normal thyroid function. Although some
      studies have suggested a connection between PCOS and autoimmune thyroiditis, no
      study indicated that PCOS is associated with Graves' disease until now. Here, we
      describe the first case report of a lean woman with normal insulin sensitivity
      presenting PCOS and Graves' disease simultaneously.

PMID- 21963739
TI  - A case of organizing pneumonia induced by tocilizumab.
AB  - A 66-year-old woman rheumatoid arthritis was treated with methotrexate and
      tocilizumab. Chest radiography revealed bilateral consolidation of an upper
      lesion in the lung. Laboratory data indicated a hepatic disorder and increased
      eosinophils. Transbronchial lung biopsy specimens showed organizing pneumonia.
      Infection was unfavorable based on culture and PCR. Drug lymphocyte stimulation
      test showed positive results both for methotrexate and tocilizumab. We were
      concerned that her pneumonitis was drug-induced. And the symptoms appeared after
      the infusion of tocilizumab. Here, we report a case of tocilizumab-induced
      organizing pneumonia.

PMID- 21963740
TI  - Chronic pulmonary thromboembolism pathologically showing homogeneous cellular
      alveolitis.
AB  - A 60-year-old man was admitted to our hospital complaining of general malaise.
      Examination of arterial blood gases on room air revealed hypoxia. Pulmonary
      function test showed restrictive abnormality. Chest high-resolution CT showed
      diffuse mosaic attenuation without evident pulmonary artery abnormality on
      contrast chest CT. Based on these findings, interstitial pneumonia or chronic
      pulmonary thromboembolism was suspected. The findings of bronchoalveolar lavage
      revealed 4.4*10(5) cells/mL, including 89.6% macrophages, 9.4% lymphocytes, and
      1.0% neutrophils. TBLB showed marked alveolitis. Moreover video-assisted
      thoracoscopic surgical biopsy was performed. Biopsies of the lung specimen showed
      focal infarct with surrounding mild mononuclear cell infiltrates (homogenous
      cellular alveolitis). (99m)Tc pulmonary perfusion and (81m)Kr ventilation
      scintigraphy showed V/Q mismatch. Furthermore, pulmonary angiography also
      revealed inadequate artery flow corresponding to the mismatch area of
      scintigraphy. Collagen vascular diseases and abnormality of coagulation factors
      were not detected. Multiple perfusion defects persisted for more than 6 months.
      Thus, finally the patient was diagnosed with chronic pulmonary thromboembolism,
      pathologically showing homogenous cellular alveolitis.

PMID- 21963742
TI  - Myelofibrosis successfully treated with prednisolone in a patient with
      pachydermoperiostosis.
AB  - Pachydermoperiostosis (PDP) is a rare disorder of bone and connective tissue
      growth. A 21-year-old man was referred to our hospital with anemia. He showed
      characteristics of PDP. Bone marrow biopsy showed myelofibrosis. Chromosomal
      abnormalities or JAK2 mutation were not found. Anemia gradually progressed, and
      he became transfusion-dependent. Oral prednisolone was initiated; it gradually
      improved his anemia and rendered the patient free of transfusion. However, other
      clinical symptoms such as clubbed fingers and skin hypertrophy remained
      unimproved. In this case, the serum concentration of vascular endothelial growth
      factor and transforming growth factor-beta levels were increased. Further
      investigation will be necessary to establish appropriate treatment strategies for
      this disease.

PMID- 21963741
TI  - A case of diabetic ketoacidosis associated with Guillain-Barre syndrome.
AB  - A 64-year-old woman was referred to our center presenting with thirst, malaise,
      and pain in both legs which occurred one week before admission. She was revealed
      to have hyperglycemia and diabetic ketoacidosis (DKA). After therapy for diabetic
      ketoacidosis was started, her blood glucose levels were improved, but urinary
      ketone body excretion persisted. Laboratory examination indicated a significant
      impairment of insulin secretion, although anti-GAD and anti-IA-2 antibody were
      not detected. After admission, she complained about weakness of lower
      extremities, which spread to her upper extremities. The diagnosis of Guillain
      Barre syndrome (GBS) was made based on the nerve conduction study and
      cerebrospinal fluid analysis. The intravenous immunoglobulin therapy was started,
      and her muscle weakness showed gradual improvement. Although the possibility that
      GBS was casually accompanied with DKA could not be completely excluded, we
      considered that DKA triggered the development of GBS in this case. Although GBS
      is a rare condition, the present case suggests that GBS should be included in the
      differential diagnosis of DKA with its atypical course.

PMID- 21963743
TI  - Successful treatment of necrotizing fasciitis in an upper extremity caused by
      Clostridium perfringens after bone marrow transplantation.
AB  - We report a 47-year-old man with acute leukemia who survived a severe case of
      necrotizing fasciitis caused by Clostridium perfringens involving his right upper
      extremity. On day 5 after stem cell transplantation, progressive local tissue
      necrosis led to septicemia and disseminated intravascular coagulation. Early
      diagnosis and prompt initiation of appropriate therapy, including surgical
      debridement and broad-spectrum antibiotics, were crucial. A recombinant
      thrombomodulin might have not only resolved the coagulation problem but also
      prevented multiple organ failure associated with the systemic inflammatory
      response.

PMID- 21963744
TI  - Leukoencephalopathy induced by low-dose methotrexate in a patient with rheumatoid
      arthritis.
AB  - We report a patient with rheumatoid arthritis (RA) who developed
      leukoencephalopathy while being treated with low-dose methotrexate (MTX). She
      suddenly developed loss of recent memory and left homonymous hemianopsia
      ascribable to the bilateral but right-predominant occipitotemporal lesions.
      Intravenous administration of dexamethasone and cessation of MTX quickly relieved
      her clinical symptoms. Low-dose MTX-induced leukoencephalopathy is a rare
      complication in RA, but is important with regard to the possibility of serious
      neurological sequellae.

PMID- 21963745
TI  - The wide range of clinical manifestations in leprous neuropathy: two case
      reports.
AB  - The present report describes two patients with leprous neuropathy diagnosed in
      Japan and manifesting with different clinical features. A 78-year-old Japanese
      man presented with a 3-year history of numbness and weakness affecting the upper
      and lower extremities. Although he did not have skin eruptions, nerve biopsy
      revealed acid-fast bacilli. Another patient, a 41-year-old Japanese-Brazilian
      man, presented with a 1-month history of numbness in the right fourth and fifth
      fingers and whole-body erythema. These cases highlight the fact that, as a result
      of worldwide travel and immigration, leprosy should still be considered in the
      differential diagnosis of neuropathy in developed countries.

PMID- 21963746
TI  - Septic arthritis caused by Mycobacterium fortuitum and Mycobacterium abscessus in
      a prosthetic knee joint: case report and review of literature.
AB  - Nontuberculous mycobacterium (NTM) is an infrequent cause of prosthetic knee
      joint infections. Simultaneous infection with different NTM species in a
      prosthetic knee joint has not been previously reported. A case of prosthetic knee
      joint infection caused by Mycobacterium abscessus and M. fortuitum is described
      in this report. The patient was successfully treated with adequate antibiotics
      and surgery. The clinical features of sixteen previously reported cases of
      prosthetic knee joint infection caused by NTM are reviewed.

PMID- 21963747
TI  - Combined Legionella and Escherichia coli lung infection after a tsunami disaster.
AB  - Pulmonary infection after a tsunami is often polymicrobial and tends to form
      chronic pyogenic lung disease, necrotizing pneumonia, and empyemas. We report a
      combined pulmonary infection of Legionella and multiple antibiotic-resistant
      Escherichia coli in a previously well 75-year-old woman following immersion in
      tsunami waters 1 km inland from the Pacific coastline following the Tohoku Region
      Pacific Coast Earthquake of 2011. She needed drainage several times and the long
      term use of multiple antibiotics according to the type of bacteria found and
      antibiotic susceptibility. We should be mindful of infections caused by multiple
      pathogens in the environment in Japan as a consequence of a tsunami disaster.

PMID- 21963748
TI  - Novel ultrasonography technique for Paget-Schroetter syndrome.

PMID- 21963749
TI  - Aortitis syndrome with vascular anomaly detected by MD-CT.

PMID- 21963751
TI  - Ventricular fibrillation following bidirectional tachycardia due to digitalis
      toxicity.

PMID- 21963750
TI  - Progressive electrocardiographic changes in arrhythmogenic right ventricular
      cardiomyopathy.

PMID- 21963752
TI  - MRI findings in nonalcoholic Wernicke's encephalopathy.

PMID- 21963753
TI  - Bilateral facial nerve palsy caused by a metastatic malignant lymphoma.

PMID- 21963754
TI  - Pneumocephalus; a rare presentation of streptococcal meningitis.

PMID- 21963755
TI  - Hemorrhagic bulla in Churg-Strauss syndrome.

PMID- 21963756
TI  - A patient with cervical swelling.

PMID- 21963757
TI  - Acute urinary retention.

PMID- 21963758
TI  - Hansen's disease: an imitator of cutaneous sarcoidosis.

PMID- 21963759
TI  - Systemic capillary leak syndrome caused by granulocyte colony-stimulating factor.

PMID- 21963761
TI  - Targeting unlesioned pharyngeal motor cortex improves swallowing in healthy
      individuals and after dysphagic stroke.
AB  - BACKGROUND & AIMS: Patients with stroke experience swallowing problems
      (dysphagia); increased risk of aspiration pneumonia, malnutrition, and
      dehydration; and have increased mortality. We investigated the behavioral and
      neurophysiological effects of a new neurostimulation technique (paired
      associative stimulation [PAS]), applied to the pharyngeal motor cortex, on
      swallowing function in healthy individuals and patients with dysphagia from
      stroke. METHODS: We examined the optimal parameters of PAS to promote plasticity
      by combining peripheral pharyngeal (electrical) with cortical stimulation. A
      virtual lesion was used as an experimental model of stroke, created with 1-Hz
      repetitive transcranial magnetic stimulation over the pharyngeal cortex in 12
      healthy individuals. We tested whether hemispheric targeting of PAS altered
      swallowing performance before applying the technique to 6 patients with severe,
      chronic dysphagia from stroke (mean of 38.8 +/- 24.4 weeks poststroke). RESULTS:
      Ten minutes of PAS to the unlesioned pharyngeal cortex reversed (bilaterally) the
      cortical suppression induced by virtual lesion (lesioned: F(1,9) = 21.347, P =
      .001; contralesional: F(1,9) = 9.648, P = .013; repeated-measures analysis of
      variance) compared with sham PAS. It promoted changes in behavior responses
      measured with a swallowing reaction time task (F(1,7) = 21.02, P = .003; repeated
      measures analysis of variance). In patients with chronic dysphagia, real PAS
      induced short-term bilateral changes in the brain; the unaffected pharyngeal
      cortex had increased excitability (P = .001; 95% confidence interval, 0.21-0.05;
      post hoc paired t test) with reduced penetration-aspiration scores and changes in
      swallowing biomechanics determined by videofluoroscopy. CONCLUSIONS: The
      beneficial neurophysiological and behavioral properties of PAS, when applied to
      unlesioned brain, provide the foundation for further investigation into the use
      of neurostimulation as a rehabilitative approach for patients with dysphagia from
      stroke.

PMID- 21963762
TI  - Characteristics of divergence excess type intermittent exotropia in Asian
      children.
AB  - BACKGROUND: Exotropia is twice as common as esotropia in Asian children, with
      divergence excess intermittent exotropia contributing more than one half of
      exotropia cases. In this study, distance-near relationships and ratios of
      accommodative convergence to accommodation (AC/A) are compared using different
      measurement methods in Asian children with divergence excess intermittent
      exotropia. METHODS: Children with intermittent exotropia and a distance deviation
      exceeding the near by at least 10(Delta) were consecutively recruited. After
      prism cover test measurements at 6 m and 33 cm, AC/A ratios were calculated using
      the heterophoria method and the gradient method with -2.0 D and +3.0 D lenses at
      6 m and 33 cm, respectively. AC/A ratios were recalculated after 1 hour of
      monocular patching. RESULTS: A total of 42 children (mean age, 6.9 years; range,
      3-16 years) were included. The mean difference between distance and near
      deviation was 22(Delta) before occlusion and 14(Delta) after (P < 0.001).
      Approximately one third had a distance-near difference <10(Delta) after
      occlusion. With the heterophoria method, 100% of patients had high AC/A ratios
      before occlusion, with 71% continuing to have high AC/A ratios after. With the
      gradient method, 52% of patients had high AC/A ratios before occlusion, with 68%
      of this subgroup continuing to have high AC/A ratios after. CONCLUSIONS: Pseudo
      divergence excess was found in one third of the subjects. More children were
      diagnosed with high AC/A ratios using the heterophoria method than with the
      gradient method. Without monocular occlusion, approximately one third of the
      children with normal AC/A ratios may be mistaken to have high AC/A ratios when
      measured with either method. Identification of high AC/A ratio exotropic patients
      is critical due to the risk of developing consecutive esotropia at near after
      strabismus surgery.

PMID- 21963763
TI  - Treatment with Bangerter filters.

PMID- 21963764
TI  - How far can hydroxyl radicals travel? An electrochemical study based on a DNA
      mediated electron transfer process.
AB  - Using photocatalytic reactive nanoparticles and DNA composite modified gold
      electrodes, exploiting the sensitivity of DNA-mediated electron transfer to base
      pair stacking, we examined the effects of DNA oxidation damage by
      photocatalytically generated hydroxyl radicals (OH) on charge transfer efficiency
      and proposed an electrochemical technique to read the effective diffusing
      distance of OH.

PMID- 21963765
TI  - 2011 ACCF/AHA Focused Update of the Guideline for the Management of Patients With
      Peripheral Artery Disease (updating the 2005 guideline): a report of the American
      College of Cardiology Foundation/American Heart Association Task Force on
      Practice Guidelines.

PMID- 21963766
TI  - Spatial frequency threshold and contrast sensitivity of an optomotor behavior are
      impaired in the Ins2Akita mouse model of diabetes.
AB  - Diabetic retinopathy can lead to progressive loss of vision and is a leading
      cause of blindness. The Ins2(Akita) mouse model of diabetes develops significant
      retinal and systemic pathology, but how these affect visual behavior is unknown.
      Here, we show that Ins2(Akita) mice have progressive, quantifiable vision
      deficits in an optomotor behavior. This mouse line is a promising model in which
      to understand the contribution of retinal neuronal injury during the chronic
      hyperglycemia and hypoinsulinemia of diabetes to deficits in vision.

PMID- 21963767
TI  - Cubic phase-forming dry powders for controlled drug delivery on mucosal surfaces.
AB  - The purpose of this study was to prepare and physicochemically characterize
      protein-loaded, glycerol monooleate (GMO)-based dry powder systems, which can be
      used for the controlled mucosal delivery of macromolecules (e.g., nasal, buccal,
      pulmonary). Bovine serum albumin (BSA)-loaded powders were prepared by spray
      drying, freeze-drying and/or spray-freezing using different types of carrier
      materials, including mannitol, polyvinyl pyrrolidone (PVP 25) and polyethylene
      glycols (PEGs). The systems were characterized by optical and polarized light
      microscopy, X-ray powder diffraction, gel electrophoresis and diffusion studies.
      The type of carrier material strongly affected the resulting particle size and
      shape. The presence of GMO effectively slowed down BSA release. Importantly,
      broad ranges of release patterns could be achieved by varying the type of
      preparation method and composition of the dry powders. In all cases, the primary
      structure of the BSA remained intact. GMO, which is a wax solid at room
      temperature, has been successfully converted into dry powder formulations that
      offer potential for the controlled mucosal delivery of proteins.

PMID- 21963768
TI  - Addition of ascorbic acid to the extracellular environment activates lipoplexes
      of a ferrocenyl lipid and promotes cell transfection.
AB  - The level of cell transfection mediated by lipoplexes formed using the ferrocenyl
      lipid bis(11-ferrocenylundecyl)dimethylammonium bromide (BFDMA) depends strongly
      on the oxidation state of the two ferrocenyl groups of the lipid (reduced BFDMA
      generally mediates high levels of transfection, but oxidized BFDMA mediates very
      low levels of transfection). Here, we report that it is possible to chemically
      transform inactive lipoplexes (formed using oxidized BFMDA) to "active"
      lipoplexes that mediate high levels of transfection by treatment with the small
      molecule reducing agent ascorbic acid (vitamin C). Our results demonstrate that
      this transformation can be conducted in cell culture media and in the presence of
      cells by addition of ascorbic acid to lipoplex-containing media in which cells
      are growing. Treatment of lipoplexes of oxidized BFDMA with ascorbic acid
      resulted in lipoplexes composed of reduced BFDMA, as characterized by UV/vis
      spectrophotometry, and lead to activated lipoplexes that mediated high levels of
      transgene expression in the COS-7, HEK 293T/17, HeLa, and NIH 3T3 cell lines.
      Characterization of internalization of DNA by confocal microscopy and
      measurements of the zeta potentials of lipoplexes suggested that these large
      differences in cell transfection result from (i) differences in the extents to
      which these lipoplexes are internalized by cells and (ii) changes in the
      oxidation state of BFDMA that occur in the extracellular environment (i.e., prior
      to internalization of lipoplexes by cells). Characterization of lipoplexes by
      small-angle neutron scattering (SANS) and by cryogenic transmission electron
      microscopy (cryo-TEM) revealed changes in the nanostructures of lipoplexes upon
      the addition of ascorbic acid, from aggregates that were generally amorphous, to
      aggregates with a more extensive multilamellar nanostructure. The results of this
      study provide guidance for the design of redox-active lipids that could lead to
      methods that enable spatial and/or temporal control of cell transfection.

PMID- 21963769
TI  - Expression of a novel dual-functional protein--the antimicrobial peptide LL-37
      fused with human acidic fibroblast growth factor in Escherichia coli.
AB  - Human acidic fibroblast growth factor (haFGF) stimulates repair of delayed
      healing which still remains a tremendously world-wide issue. However, most of the
      patients with delayed healings have to face another creeping problem - microbial
      infection, which is one of the most frequent complications that still lead to
      wound healing failure. LL-37/hCAP-18 is the only cathelicidin-derived
      antimicrobial peptide found in human with a wide range of antimicrobial
      activities. In the present study, a novel hybrid protein combining LL-37 with
      haFGF was designed. The DNA sequence encoding recombination fusion protein LL-37
      haFGF was subcloned into the pET-21b vector for protein expression in Escherichia
      coli strain BL21 (DE3). The recombinant protein was expressed as a His-tagged
      protein and purified using a combination of Ni affinity and CM-Sepharose
      chromatography at a purity of 95.43% as detected by RP-HPLC and sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Antimicrobial activity
      assays showed that the purified LL-37-haFGF had improved antimicrobial activities
      in vitro compared with LL-37. Methylthiazoletetrazolium (MTT) assay showed that
      the purified LL-37-haFGF also had a distinct mitogenic activity in NIH 3T3 cells.
      These data suggests the recombinant protein LL-37-haFGF has pharmaceutical
      potential for applications in wound healing.

PMID- 21963770
TI  - Heat stability of Proteobacterial PII protein facilitate purification using a
      single chromatography step.
AB  - The P(II) proteins comprise a family of widely distributed signal transduction
      proteins that integrate the signals of cellular nitrogen, carbon and energy
      status, and then regulate, by protein-protein interaction, the activity of a
      variety of target proteins including enzymes, transcriptional regulators and
      membrane transporters. We have previously shown that the P(II) proteins from
      Azospirillum brasilense, GlnB and GlnZ, do not alter their migration behavior
      under native gel electrophoresis following incubated for a few minutes at 95
      degrees C. This data suggested that P(II) proteins were either resistant to high
      temperatures and/or that they could return to their native state after having
      been unfolded by heat. Here we used (1)H NMR to show that the A. brasilense GlnB
      is stable up to 70 degrees C. The melting temperature (Tm) of GlnB was determined
      to be 84 degrees C using the fluorescent dye Sypro-Orange. P(II) proteins from
      other Proteobacteria also showed a high Tm. We exploited the thermo stability of
      P(II) by introducing a thermal treatment step in the P(II) purification protocol,
      this step significantly improved the homogeneity of A. brasilense GlnB and GlnZ,
      Herbaspirillum seropedicae GlnB and GlnK, and of Escherichia coli GlnK. Only a
      single chromatography step was necessary to obtain homogeneities higher than 95%.
      NMR(1) and in vitro uridylylation analysis showed that A. brasilense GlnB
      purified using the thermal treatment maintained its folding and activity. The
      purification protocol described here can facilitate the study of P(II) protein
      family members.

PMID- 21963771
TI  - Indication of intracellular physiological pH changes by L-cysteine-coated CdTe
      quantum dots with an acute alteration in emission color.
AB  - A novel quantum dots (QDs) based biosensor was developed to monitor physiological
      pH changes in both fixed and living cells by means of pH-dependent emission color
      of the QDs. In our system, the nominally single-sized colloidal solution samples
      of the L-cysteine-capped CdTe QDs with intrinsically broadened size distributions
      were prepared by employing aqueous synthesis technique. The quench of
      fluorescence intensities of the QDs with a 16 nm red shift of the emission
      maximum and a color change from green to yellow was observed with a slight pH
      decrease (from 7.0 to 6.8) in the system. This pH-dependent emission could be
      attributed to the efficient exciton energy transfer from smaller QDs to larger
      ones, which was controlled by electrostatic-tuned aggregation/disaggregation
      (low/high pH values) processes of the QDs. In addition to high stability, the
      emission shift of the QDs was reversible for at least one cycle under optimal
      conditions. Our pH biosensor may find potential application for monitoring the
      intracellular pH changes in both physiological and pathological conditions.

PMID- 21963772
TI  - Infestin 1R, an intestinal subtilisin inhibitor from Triatoma infestans able to
      impair mammalian cell invasion by Trypanosoma cruzi.
AB  - Infestins are Kazal-type serine protease inhibitors described in the midgut of
      Triatoma infestans, Chagas disease vector. Of all infestins, only infestin 1R
      (INF1R) does not control host blood coagulation, due to its inhibitory
      specificity for chymotrypsin-like proteases. We further investigated the effect
      of INF1R on cell infection by Trypanosoma cruzi. The importance of INF1R reactive
      site to inhibit T. cruzi cell invasion was confirmed using 1RSFTI, a synthetic
      cyclic peptide containing the inhibitor reactive site region hybridized to the
      Sunflower Trypsin Inhibitor-1 (SFTI-1). Our results suggest that INF1R
      efficiently inhibited parasite cell invasion. For the first time, a serine
      protease inhibitor, derived from T. infestans, was shown to impair cell invasion
      by T. cruzi, representing possible new target in parasite cell invasion.

PMID- 21963773
TI  - In vivo antitumor effect of cromolyn in PEGylated liposomes for pancreatic
      cancer.
AB  - A PEGylated liposomal formulation of cromolyn, composed of
      dipalmitoylphosphatidylcholine (DPPC), dimyristoylphosphatidylcholine (DMPC),
      distearoylphosphatidylcholine (DSPC) and 1,2-distearoyl-sn-glycero-3-phospho
      ethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-mPEG2000), has been
      developed with the purpose of improving the antitumor activity of cromolyn for
      human pancreatic adenocarcinoma. In stability study, the amount of proteins
      adsorbed onto the PEGylated liposomes encapsulating cromolyn was 4.5-fold lower
      than the non-PEGylated liposome. In vitro study showed that the cromolyn in
      PEGylated liposome exhibited better anti-proliferative effect in BxPC-3 cells
      than in Panc-1 cells, which indicates higher level of endogenous S100P protein in
      BxPC-3 cells than in Panc-1 cells as a target protein for this drug. Moreover,
      the combination of cromolyn with gemcitabine in PEGylated liposomes demonstrated
      the strongest cytotoxicity to BxPC-3 pancreatic cancer cells in vitro and the
      highest anti-tumor activity against the BxPC-3 tumor bearing nude mice in vivo.
      Thus, this PEGylated liposomal formulation of cromolyn is expected to provide a
      novel approach to the treatment of pancreatic cancer in the future.

PMID- 21963774
TI  - Poly-e-caprolactone based formulations for drug delivery and tissue engineering:
      A review.
AB  - Biodegradable polymer based novel drug delivery systems have provided many
      avenues to improve therapeutic efficacy and pharmacokinetic parameters of
      medicinal entities. Among synthetic biodegradable polymer, poly-e-caprolactone
      (PCL) is a polymer with very low glass transition temperature and melting point.
      Owing to its amicable nature and tailorable properties it has been trialed in
      almost all novel drug delivery systems and tissue engineering application in
      use/investigated so far. This review aims to provide an up to date of drugs
      incorporated in different PCL based formulations, their purpose and brief
      outcomes. Demonstrated PCL formulations with or without drugs, intended for drug
      delivery and/or tissue engineering application such as microsphere,
      nanoparticles, scaffolds, films, fibers, micelles etc. are categorized based on
      method of preparation.

PMID- 21963775
TI  - Behavioral robustness: an emergent phenomenon by means of distributed mechanisms
      and neurodynamic determinacy.
AB  - Theoretical discussions and computational models of bio-inspired embodied and
      situated agents are introduced in this article capturing in simplified form the
      dynamical essence of robust, yet adaptive behavior. This article analyzes the
      general problem of how the dynamical coupling between internal control (brain),
      body and environment is used in the generation of specific behaviors. Based on
      the Evolutionary Robotics (ER) paradigm, four computational models are described
      to support discussions including descriptions on performance after a series of
      structural, sensorimotor or mutational perturbations, or are developed in the
      absence of them. Experimental results suggest that 'dynamic determinacy' - i.e.
      the continuous presence of a unique dynamical attractor that must be chased
      during functional behaviors - is a common dynamic phenomenon in the analyzed
      robust and adaptive agents. These agents show dynamical states that are
      definitely and unequivocally characterized via transient dynamics toward a
      unique, yet moving attractor at neural level for coherent actions. This
      determinacy emerges as a control strategy rooted on behavioral couplings and
      relies on mechanisms that are distributed on brain, body and environment.
      Different ways to induce further distribution of behavioral mechanisms are also
      discussed in this paper from a bio-inspired ER perspective.

PMID- 21963776
TI  - Child care health consultants still in demand: pediatric nurses are an asset.

PMID- 21963777
TI  - Pediatric medical line safety: the prevalence and severity of medical line
      entanglements.
AB  - The purpose of this cross-sectional study was to describe the prevalence and
      severity of medical line entanglements among pediatric patients (N = 486). Most
      patients, with ages from birth to 6 years, had at least 1 medical line (n = 444,
      91%), and 294 children (60%) had 2 to 11 medical lines. Observed entanglements
      included lines around body parts (n = 31), lines under the body (n = 71), and
      lines tangled with other lines (n = 50). One third of the children were at risk
      for adverse events due to entanglements, and 1 patient actually experienced real
      harm.

PMID- 21963778
TI  - Increasing the safety of blind gastric tube placement in pediatric patients: the
      design and testing of a procedure using a carbon dioxide detection device.
AB  - The accidental placement of feeding tubes into the airway is a rare but serious
      complication of blind feeding tube placement in pediatrics. A method using a
      colorimetric carbon dioxide detector has been tested as a means of decreasing the
      risk of inadvertent airway placement of gastric tubes in adults, but to date, a
      similar study has not been accomplished in pediatric patients. This study sought
      to evaluate the efficacy of a procedure using the colorimetric device during
      blind gastric tube placement in children. The results demonstrated that the study
      procedure using the device is effective in detecting inadvertent tube placement
      into the lung in the pediatric population.

PMID- 21963779
TI  - High-frequency electromagnetic dynamics properties of THP1 cells using scanning
      microwave microscopy.
AB  - Microwave measurements combined with scanning probe microscopy is a novel tool to
      explore high-localized mechanical and electrical properties of biological
      species. Complex permittivities and permeabilities are detected through slight
      variations of an incident microwave signal. Here we report the high-frequency
      dependence of the electromagnetic dynamic characteristics in human monocytic
      leukemia cells (THP1) through local measurements by scanning microwave microscopy
      (SMM). The amplitude and phase images were shown to depend on the applied
      resonance frequency. While the amplitude yields information about the resistivity
      determined by the water and the ionic strength, the phase information reflects
      the dielectric losses arising from the fluid density.

PMID- 21963780
TI  - Imaging and strain analysis of nano-scale SiGe structures by tip-enhanced Raman
      spectroscopy.
AB  - The spatial resolution and high sensitivity of tip-enhanced Raman spectroscopy
      allows the characterization of surface features on a nano-scale. This technique
      is used to visualize silicon-based structures, which are similar in width to the
      transistor channels in present leading-edge CMOS devices. The reduction of the
      intensive far-field background signal is crucial for detecting the weak near
      field contributions and requires beside a careful alignment of laser polarization
      and tip axis also the consideration of the crystalline sample orientation.
      Despite the chemical identity of the investigated sample surface, the structures
      can be visualized by the shift of the Raman peak positions due to the patterning
      induced change of the stress distribution within lines and substrate layer. From
      the measured peak positions the intrinsic stress within the lines is calculated
      and compared with results obtained by finite element modeling. The results
      demonstrate the capability of the tip-enhanced Raman technique for strain
      analysis on a sub-50nm scale.

PMID- 21963783
TI  - Hepatic and muscular effects of different dietary fat content in VLCAD deficient
      mice.
AB  - BACKGROUND: Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is the most
      common long-chain fatty acid oxidation defect presenting with heterogeneous
      clinical phenotypes. Dietary fat plays a crucial role in disease pathogenesis and
      fat restriction is a common treatment measure. We here investigate the hepatic
      and muscular effects of a fat-enriched and a fat-restricted diet. METHODS: VLCAD
      knock-out (KO) and wild-type (WT) mice are subjected to a fat-rich (10.6%), a fat
      reduced (2.6%) or a regular mouse diet (5.1%) for 5 weeks. Analyses are performed
      at rest and after one hour exercise on a treadmill. Acylcarnitines in muscle as
      well as lipid and glycogen content in muscle and liver are quantified. Expression
      of genes involved in lipogenesis is measured by Real-Time-PCR. RESULTS: At rest,
      VLCAD KO mice develop no clinical phenotype with all three diets, but importantly
      VLCAD KO mice cannot perform one hour exercise as compared to WT, this is
      especially apparent in mice with a fat-reduced diet. Moreover, changes in dietary
      fat content induce a significant increase in muscular long-chain acylcarnitines
      and hepatic lipid content in VLCAD KO mice after exercise. A fat-reduced diet up
      regulates hepatic lipogenesis at rest. At the same time, muscular glycogen is
      significantly lower than in WT. CONCLUSIONS: We here demonstrate that a fat
      reduced and carbohydrate-enriched diet does not prevent the myopathic phenotype
      in VLCAD KO mice. An increase in dietary fat is safe at rest with respect to the
      muscle but results in a significant muscular acylcarnitine increase after
      exercise.

PMID- 21963784
TI  - Newborn screening for Pompe disease in Japan.
AB  - Pompe disease is caused by a deficiency of acid alpha-glucosidase (GAA) that
      results in glycogen accumulation, primarily in muscle. Newborn screening (NBS)
      for Pompe disease has been initiated in Taiwan and is reportedly successful.
      However, the comparatively high frequency of pseudodeficiency allele makes NBS
      for Pompe disease complicated in Taiwan. To investigate the feasibility of NBS
      for Pompe disease in Japan, we obtained dried blood spots (DBSs) from 496 healthy
      Japanese controls, 29 Japanese patients with Pompe disease, and five obligate
      carriers, and assayed GAA activity under the following conditions: (1) total GAA
      measured at pH 3.8, (2) GAA measured at pH 3.8 in the presence of acarbose, and
      (3) neutral glucosidase activity (NAG) measured at pH 7.0 without acarbose. The %
      inhibition and NAG/GAA ratio were calculated. For screening, samples with GAA<8%
      of the normal mean, % inhibition>60%, and NAG/GAA ratio>30 were considered to be
      positive. Two false positive cases (0.3%) were found, one was a healthy
      homozygote of pseudodeficiency allele (c.1726G>A). The low false-positive rate
      suggests that NBS for Pompe disease is feasible in Japan.

PMID- 21963785
TI  - Intragenic deletion as a novel type of mutation in Wolman disease.
AB  - Two clinically distinct disorders, Wolman disease (WD) and cholesteryl ester
      storage disease (CESD), are allelic autosomal recessive disorders caused by
      different mutations in lysosomal acid lipase (LIPA) which encodes for an
      essential enzyme involved in the hydrolysis of intracellular cholesteryl esters
      and triglycerides. We describe a case of lysosomal acid lipase deficiency in an
      infant with WD and report on a novel mutation type, intragenic deletion.

PMID- 21963786
TI  - Spinal microglia initiate and maintain hyperalgesia in a rat model of chronic
      pancreatitis.
AB  - BACKGROUND & AIMS: The chronic, persistent pain associated with chronic
      pancreatitis (CP) has many characteristics of neuropathic pain, initiated and
      maintained by the activation of spinal microglia. We investigated whether
      activated microglia in the thoracic spinal cord contribute to chronic pain in a
      rat model of CP. METHODS: CP was induced in Sprague-Dawley rats by an intraductal
      injection of 2% trinitrobenzene sulfonic acid. Hyperalgesia was assessed by the
      measurement of mechanical sensitivity of the abdomen and nocifensive behavior to
      electrical stimulation of the pancreas. Three weeks after induction of CP, spinal
      samples were analyzed by immunostaining and immunoblot analyses for levels of
      CD11 (a marker of microglia, determined with the antibody OX42) and
      phosphorylated p38 (P-p38, a marker of activation of p38 mitogen-activated
      protein kinase signaling). We examined the effects of minocycline (inhibitor of
      microglia) and fractalkine (microglia-activating factor) on visceral hyperalgesia
      in rats with CP. RESULTS: Rats with CP had increased sensitivity and nociceptive
      behaviors to mechanical probing of the abdomen and electrical stimulation of the
      pancreas. The dorsal horn of the thoracic spinal cords of rats with CP contained
      activated microglia (based on increased staining with OX42), with an ameboid
      appearance. Levels of P-p38 increased in rats with CP and colocalized with OX42
      positive cells. Intrathecal injection of minocycline reversed and prevented the
      increase of nocifensive behaviors and levels of P-p38 in rats with CP.
      Fractalkine induced hyperalgesia in rats without CP, which was blocked by
      minocycline. CONCLUSIONS: Activated spinal microglia have important roles in
      maintaining and initiating chronic pain in a rat model of CP. Microglia might be
      a target for treatment of hyperalgesia caused by pancreatic inflammation.

PMID- 21963788
TI  - Molecular and functional characterization of an Entamoeba histolytica protein
      (EhMLCI) with features of a myosin essential light chain.
AB  - Entamoeba histolytica, a protozoan parasite of humans, relays on its striking
      motility to survive and invade host tissues. Characterization of the molecular
      components involved in motile processes is crucial to understand its
      pathogenicity. Although protein components of myosin II hexamers have been
      predicted from E. histolytica genome data, only a heavy chain of myosin, EhmhcA,
      has been characterized so far. We have cloned an E. histolytica cDNA sequence
      that best matched Dictyostelium discoideum myosin essential light chain and found
      that the cloned sequence is transcribed as an mRNA of 0.445 kb which could encode
      a protein of 16.88 kDa, within the predicted range for a myosin light chain. In
      silico analyses revealed that the protein sequence, named EhMLCI, shows two
      consensus domains for binding MHC, but lacks the N-terminal sequence for actin
      binding, as in A2 type myosin essential light chains. A single EF-hand calcium
      binding domain was identified in the C-terminus and several high score
      predictability sites for serine and tyrosine phosphorylation. Antibodies to
      recombinant EhMLCI identified two proteins of approximately 17 and 15 kDa in
      trophozoite extracts, the latter phophorylated in tyrosines. Serine
      phosphorylation was not detected. Immunomicroscopy revealed EhMLCI cortical and
      cytoplasmic distribution in trophozoites and true colocalization with EhmhcA
      determined by PCC. Co-immunoprecipitation corroborated EhMLCI interaction with
      EhmhcA. EhMLCI was also localized in actomyosin-containing complexes.
      Differential partition of phospho-tyrosinated EhMLCI into cell fractions
      containing the soluble form of EhmhcA and its lack of serine phosphorylation
      suggest its possible participation in a novel down regulatory mechanism of myosin
      II activity in E. histolytica.

PMID- 21963789
TI  - Validity of a self-administered food frequency questionnaire for middle-aged
      urban cancer screenees: comparison with 4-day weighed dietary records.
AB  - BACKGROUND: The validity of estimates of dietary intake calculated using a food
      frequency questionnaire (FFQ) depends on the specific population. The 138-item
      FFQ used in the 5-year follow-up survey for the Japan Public Health Center-based
      Prospective Study was initially developed for and validated in rural residents.
      However, the validity of estimates based on this FFQ for urban residents, whose
      diet and lifestyle differ from those of rural residents, has not been clarified.
      We examined the validity of ranking individuals according to level of dietary
      consumption, as estimated by this FFQ, among an urban population in Japan.
      METHODS: Among 896 candidates randomly selected from examinees of cancer
      screening provided by the National Cancer Center, Japan, 144 participated in the
      study. In 2007-2008, at an average 2.7 years after cancer screening, participants
      were asked to respond to the questionnaire and to provide 4-day weighed diet
      records (4d-DRs) for use as the reference intake. Spearman correlation
      coefficients (CCs) between the FFQ and 4d-DR estimates were calculated, after
      correction for intraindividual variation of 4d-DRs. RESULTS: The median (range)
      deattenuated CC for men and women was 0.57 (0.23 to 0.89) and 0.47 (0.08 to
      0.94), respectively, across 45 nutrients and 0.51 (0.10 to 0.98) and 0.51 (-0.36
      to 0.88) for 43 food groups. CONCLUSIONS: Although the FFQ was developed for a
      rural population, it provided reasonably valid measures of consumption for many
      nutrients and food groups in middle-aged screenees living in urban areas in
      Japan.

PMID- 21963787
TI  - Campylobacter jejuni induces colitis through activation of mammalian target of
      rapamycin signaling.
AB  - BACKGROUND & AIMS: Campylobacter jejuni is the worldwide leading cause of
      bacterial-induced enteritis. The molecular and cellular events that lead to
      campylobacteriosis are poorly understood. We identify mammalian target of
      rapamycin (mTOR) as a signaling pathway that leads to C jejuni-induced intestinal
      inflammation. METHODS: Germ-free (control) or conventionally derived Il10(-/-)
      mice that express enhanced green fluorescent protein (EGFP) under the control of
      nuclear factor kappaB (Il10(-/-); NF-kappaB(EGFP) mice) were infected with C
      jejuni (10(9) colony-forming units/mouse) for 12 days; their responses were
      determined using histologic, semiquantitative reverse-transcription polymerase
      chain reaction, fluorescence in situ hybridization, transmission electron
      microscopy, and tissue culture analyses. mTOR signaling was blocked by daily
      intraperitoneal injections of the pharmacologic inhibitor rapamycin (1.5 mg/kg).
      CD4(+) T cells were depleted by intraperitoneal injections of antibodies against
      CD4 (0.5 mg/mouse every 3 days). Bacterial survival in splenocytes was measured
      using a gentamycin killing assay. RESULTS: C jejuni induced intestinal
      inflammation, which correlated with activation of mTOR signaling and neutrophil
      infiltration. The inflamed intestines of these mice had increased levels of
      interleukin-1beta, Cxcl2, interleukin-17a, and EGFP; C jejuni localized to colons
      and extraintestinal tissues of infected Il10(-/-); NF-kappaB(EGFP) mice compared
      with controls. Rapamycin, administered before or after introduction of C jejuni,
      blocked C jejuni-induced intestinal inflammation and bacterial accumulation.
      LC3II processing and killing of C jejuni were increased in splenocytes incubated
      with rapamycin compared with controls. CONCLUSIONS: mTOR signaling mediates C
      jejuni-induced colitis in Il10(-/-) mice, independently of T-cell activation.
      Factors involved in mTOR signaling might be therapeutic targets for
      campylobacteriosis.

PMID- 21963790
TI  - Neospora caninum: comparative gene expression profiling of Neospora caninum wild
      type and a temperature sensitive clone.
AB  - To understand the genetic basis of virulence, gene expression profiles of a
      temperature-sensitive clone (NCts-8, relatively avirulent) and its wild type (NC
      1) of Neospora caninum were characterized and compared using a high-density
      microarray with approximately 63,000 distinct oligonucleotides. This microarray
      consists of 5692 unique N. caninum sequences, including 1980 Tentative Consensus
      sequences and 3712 singleton ESTs from the TIGR N. caninum Gene Index (NCGI,
      release 5.0). Each sequence was represented by 11 distinct 60mer oligonucleotides
      synthesized in situ on the microarray. The results showed that 111 genes were
      significantly repressed and no up-regulated genes were identified in the NCts-8
      clone. The level of 10 randomly selected genes from the repressed genes was
      confirmed using real-time RT-PCR. Of the 111 repressed genes, 58 were
      hypothetical protein products and 53 were annotated genes. Over 70% of the
      repressed genes identified in this study are clustered on five chromosomes (I,
      VII, VIII, X and XII). These results suggest that the down-regulated genes may be
      in part responsible for the reduced pathogenesis of NCts-8; further
      characterization of the regulated genes may aid in understanding of molecular
      basis of virulence and development of countermeasures against neosporosis.

PMID- 21963791
TI  - Light sheet microscopy for real-time developmental biology.
AB  - Within only a few short years, light sheet microscopy has contributed
      substantially to the emerging field of real-time developmental biology. Low photo
      toxicity and high-speed multiview acquisition have made selective plane
      illumination microscopy (SPIM) a popular choice for studies of organ
      morphogenesis and function in zebrafish, Drosophila, and other model organisms. A
      multitude of different light sheet microscopes have emerged for the noninvasive
      imaging of specimens ranging from single molecules to cells, tissues, and entire
      embryos. In particular, developmental biology can benefit from the ability to
      watch developmental events occur in real time in an entire embryo, thereby
      advancing our understanding on how cells form tissues and organs. However, it
      presents a new challenge to our existing data and image processing tools. This
      review gives an overview of where we stand as light sheet microscopy branches
      out, explores new areas, and becomes more specialized.

PMID- 21963792
TI  - Structural characterization of inhibitor complexes with checkpoint kinase 2
      (Chk2), a drug target for cancer therapy.
AB  - Chk2 (checkpoint kinase 2) is a serine/threonine kinase that participates in a
      series of signaling networks responsible for maintaining genomic integrity and
      responding to DNA damage. The development of selective Chk2 inhibitors has
      recently attracted much interest as a means of sensitizing cancer cells to
      current DNA-damaging agents used in the treatment of cancer. Additionally,
      selective Chk2 inhibitors may reduce p53-mediated apoptosis in normal tissues,
      thereby helping to mitigate adverse side effects from chemotherapy and radiation.
      Thus far, relatively few selective inhibitors of Chk2 have been described and
      none have yet progressed into clinical trials. Here, we report crystal structures
      of the catalytic domain of Chk2 in complex with a novel series of potent and
      selective small molecule inhibitors. These compounds exhibit nanomolar potencies
      and are selective for Chk2 over Chk1. The structures reported here elucidate the
      binding modes of these inhibitors to Chk2 and provide information that can be
      exploited for the structure-assisted design of novel chemotherapeutics.

PMID- 21963793
TI  - Following the course of pre-implantation embryo patterning by non-linear
      microscopy.
AB  - Embryo patterning is subject to intense investigation. So far only large,
      microscopically obvious structures like polar body, cleavage furrow, pro-nucleus
      shape can be evaluated in the intact embryo. Using non-linear microscopic
      techniques, the present work describes new methodologies to evaluate pre
      implantation mouse embryo patterning. Third Harmonic Generation (THG) imaging, by
      detecting mitochondrial/lipid body structures, could provide valuable and
      complementary information as to the energetic status of pre-implantation embryos,
      time evolution of different developmental stages, embryo polarization prior to
      mitotic division and blastomere equivalence. Quantification of THG imaging
      detected highest signalling in the 2-cell stage embryos, while evaluating a 12
      18% difference between blastomeres at the 8-cell stage embryos. Such a
      methodology provides novel, non-intrusive imaging assays to follow up
      intracellular structural patterning associated with the energetic status of a
      developing embryo, which could be successfully used for embryo selection during
      the in vitro fertilization process.

PMID- 21963795
TI  - FTIR spectroscopy: A new diagnostic tool to aid DNA analysis from heated bone.
AB  - Deoxyribonucleic acid (DNA) extracted from skeletal tissue can be invaluable in
      genetic profiling applications, as it is often the only source available. Like
      all forensic samples, skeletal tissue may have been exposed to a variety of
      environmental insults, including heat. This study has focussed upon
      characterising changes in the material properties of bone that has been
      compromised by controlled heat treatments. These changes were then examined in
      relation to the subsequent success or failure of nuclear DNA (nDNA)
      amplification, using a range of differently sized amplicons, relevant to
      alternate profiling strategies. The results presented demonstrate that the
      ability to amplify nDNA correlates well with particular changes in mineral and
      organic content of bone. As such, we propose the application of a 'diagnostic
      triage tool' that can be performed quickly and at low cost on individual bone
      samples, in order to determine whether nDNA analysis is likely to be a viable
      option.

PMID- 21963794
TI  - UCSF Chimera, MODELLER, and IMP: an integrated modeling system.
AB  - Structural modeling of macromolecular complexes greatly benefits from interactive
      visualization capabilities. Here we present the integration of several modeling
      tools into UCSF Chimera. These include comparative modeling by MODELLER,
      simultaneous fitting of multiple components into electron microscopy density maps
      by IMP MultiFit, computing of small-angle X-ray scattering profiles and fitting
      of the corresponding experimental profile by IMP FoXS, and assessment of amino
      acid sidechain conformations based on rotamer probabilities and local
      interactions by Chimera.

PMID- 21963796
TI  - Bilateral upper arm swelling and weight loss.

PMID- 21963797
TI  - Upper gastrointestinal bleeding caused by a duodenal submucosal tumor.

PMID- 21963798
TI  - Not all duodenal "scalloping" is celiac disease.

PMID- 21963799
TI  - The kidney speaks: interpreting urinary sodium and osmolality.

PMID- 21963800
TI  - The development of vaccines: how the past led to the future.
AB  - The history of vaccine development has seen many accomplishments, but there are
      still many diseases that are difficult to target, and new technologies are being
      brought to bear on them. Past successes have been largely due to elicitation of
      protective antibodies based on predictions made from the study of animal models,
      natural infections and seroepidemiology. Those predictions have often been
      correct, as indicated by the decline of many infections for which vaccines have
      been made over the past 200 years.

PMID- 21963802
TI  - Bacterial toxins: breaking the barrier.

PMID- 21963801
TI  - Microbial ultraviolet sunscreens.
AB  - Exposure to the shortest wavelengths in sunlight, ultraviolet light, constitutes
      a deleterious ecological factor for many microorganisms. The use of secondary
      metabolites as sunscreens has emerged as an important photoprotective mechanism
      in certain groups of large-celled microorganisms, such as cyanobacteria, fungi
      and many protists. In this Review, we describe our current understanding of
      microbial 'sunscreen' compounds, including scytonemin, the mycosporines and the
      naphthalene-based melanins. Study of these sunscreens has led to the discovery of
      new classes of compounds, new metabolic pathways, a deeper understanding of
      microbial photobiology and the potential for dermatological or biomedical
      applications.

PMID- 21963804
TI  - Fungal pathogenesis: hungry fungus eats nematode.

PMID- 21963803
TI  - Microbial degradation of aromatic compounds - from one strategy to four.
AB  - Aromatic compounds are both common growth substrates for microorganisms and
      prominent environmental pollutants. The crucial step in their degradation is
      overcoming the resonance energy that stabilizes the ring structure. The classical
      strategy for degradation comprises an attack by oxygenases that hydroxylate and
      finally cleave the ring with the help of activated molecular oxygen. Here, we
      describe three alternative strategies used by microorganisms to degrade aromatic
      compounds. All three of these methods involve the use of CoA thioesters and ring
      cleavage by hydrolysis. However, these strategies are based on different ring
      activation mechanisms that consist of either formation of a non-aromatic ring
      epoxide under oxic conditions, or reduction of the aromatic ring under anoxic
      conditions using one of two completely different systems.

PMID- 21963805
TI  - Skp2: a novel potential therapeutic target for prostate cancer.
AB  - Prostate cancer is the most frequently diagnosed tumor in men and the second most
      common cause of cancer-related death for males in the United States. It has been
      shown that multiple signaling pathways are involved in the pathogenesis of
      prostate cancer, such as androgen receptor (AR), Akt, Wnt, Hedgehog (Hh) and
      Notch. Recently, burgeoning amounts of evidence have implicated that the F-box
      protein Skp2 (S-phase kinase associated protein 2), a well-characterized
      oncoprotein, also plays a critical role in the development and progression of
      prostate cancer. Therefore, this review discusses the recent literature regarding
      the function and regulation of Skp2 in the pathogenesis of prostate cancer.
      Furthermore, we highlight that Skp2 may represent an attractive therapeutic
      target, thus warrants further development of agents to target Skp2, which could
      have significant therapeutic impact on prostate cancer.

PMID- 21963806
TI  - Mechanism of sappanchalcone-induced growth inhibition and apoptosis in human oral
      cancer cells.
AB  - Sappanchalcone, a flavonoid extracted from Caesalpinia sappan, exhibits
      cytoprotective activity, but the molecular basis for the anticancer effect of
      sappanchalcone has not been reported. In this study, we examined whether
      sappanchalcone could inhibit the growth of human primary and metastatic oral
      cancer cells, and we analyzed the signaling pathway underlying the apoptotic
      effects of the compound in this process using 3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide (MTT) assays, fluorescence microscopy, flow
      cytometry, and Western blotting. Sappanchalcone-treated oral cancer cells showed
      an increased cytosolic level of cytochrome c, downregulated Bcl-2 expression,
      upregulated Bax and p53 expression, caspase-3 and -9 activation, and poly (ADP
      ribose) polymerase cleavage. Furthermore, sappanchalcone induced activation of
      p38, extracellular signal-regulated kinase (ERK), c-Jun amino-terminal kinase
      (JNK), and Nuclear factor k B (NF-kappaB), as demonstrated by the phosphorylation
      of each mitogen-activated protein kinases (MAPKs), the degradation of inhibitor
      of NF-kappaalpha (IkappaB-alpha), increased expression of nuclear p65, and NF
      kappaB-DNA binding. Inhibition of the expression of p38, ERK, JNK, and NF-kappaB
      by pharmacological inhibitors reversed sappanchalcone-induced growth inhibition
      and apoptosis. These results provide the first evidence that sappanchalcone
      suppresses oral cancer cell growth and induces apoptosis through the activation
      of p53-dependent mitochondrial, p38, ERK, JNK, and NF-kappaB signaling. Thus, it
      has potential as a chemotherapeutic agent for oral cancer.

PMID- 21963807
TI  - Potential of coculture in vitro models to study inflammatory and sensitizing
      effects of particles on the lung.
AB  - Exposure to particulate matter (PM) like nanoparticles (NPs) has increased in the
      last century due to increased combustion processes, road traffic, etc. In
      addition, the progress in chemical and cosmetic industry led to many new
      compounds, e.g. fragrances, which humans are exposed to every day. Many chemicals
      are known to act as contact and some as respiratory sensitizers, causing allergic
      reactions. Exposure to small particles of less than 100 nm in diameter is linked
      with an increased risk of respiratory diseases, such as asthma or rhinitis. To
      date already more than 1000 customer products contain eNPs without knowing much
      about the health effects. In comparison to chemicals, the mechanisms by which PM
      and eNPs can cause sensitization are still not fully understood. Validated and
      regulatory accepted in vitro models to assess this hazard in its full range are
      still missing. While a huge number of animal studies contributed to our knowledge
      about sensitization processes, knowledge on involved cellular mechanisms is still
      limited. In this review relevant in vitro models to study and elucidate these
      mechanisms in more detail are presented and their potential to serve as part of a
      tiered testing strategy is discussed.

PMID- 21963808
TI  - Different AhR binding sites of diterpenoid ligands from Andrographis paniculata
      caused differential CYP1A1 induction in primary culture in mouse hepatocytes.
AB  - Andrographis paniculata has been employed as a folklore remedy. Andrographolide
      (Andro), 14-deoxy-11,12-didehydroandrographolide (DHA), andrographiside (AS), and
      neoandrographolide (Neo), are major diterpenoids isolated from this plant. In the
      present study, influence of the four diterpenoids on CYP1A1 mRNA expression was
      investigated in primary cultured mouse hepatocytes. Additionally, binding of
      these compounds to aryl hydrocarbon receptor (AhR) was examined using molecular
      docking analysis to clarify mechanism of CYP1A1 induction. Andro and DHA induced
      CYP1A1 expression by itself, and co-treatment with a CYP1A1 inducer (BNF, beta
      naphthoflavone) showed a synergistic increase of CYP1A1 expression. Andro
      demonstrated higher enhancing activity than DHA at every similar concentration.
      On the other hand, Neo suppressed BNF-induced CYP1A1 expression, but AS did not
      modify the induction. Results from molecular docking analysis of BNF and four
      diterpenoids on ligand binding domain of AhR were consistent with levels of
      CYP1A1 mRNA expressions. Furthermore, difference of binding sites of BNF in the
      presence of diterpenoids might affect the synergism or inhibition of CYP1A1
      expression. These results suggest that use of A. paniculata as a health
      supplement should be concerned in term of herb-drugs interactions or risk of
      carcinogenesis, according to its ability to influence CYP1A1 expression.

PMID- 21963809
TI  - Reproducibility and influence of hand rotation on computer-aided joint space
      analysis.
AB  - OBJECTIVES: Computer-aided joint space analysis (CAJSA) is a recently developed,
      semi-automated tool to aid in the measurement of joint space margins based on
      hand radiographs. The objective of this study is to verify the potential effect
      of hand rotation during X-ray imaging on the measurement of joint space width
      using CAJSA and to evaluate the reproducibility of the CAJSA technique in healthy
      subjects and in patients with rheumatoid arthritis. METHODS: All joint space
      distance (JSD) measurements were performed using CAJSA-technology at the
      metacarpophalangeal articulation based on conventional and digital hand
      radiographs. RESULTS: I. Hand rotation showed an effect on the reproducibility
      with CV ranging between 0.39% (angulation 1 degrees ) and 1.66% (angulation 19
      degrees ). II. Regarding the overall reproducibility of the CAJSA method, the
      intra-radiograph reproducibility of JSD was calculated with CV=0.54% for
      conventional images and CV=0.38% for digital images. The inter-radiograph
      reproducibility error was observed with CV=0.66% (conventional images) and
      CV=0.63% (digital images). III. The study revealed a reproducibility for CAJSA
      measurements in RA ranging between 0.37% (JSD-MCP ring finger; van der Heijde
      modification of the Sharp method score 1) to 1.37% (JSD-MCP index finger; van der
      Heijde-modification of the Sharp method score 3). CONCLUSION: CAJSA measures JSD
      at the metacarpophalangeal articulation with high reproducibility in healthy
      subjects and in patients with differing stages of rheumatoid arthritis.
      Additional findings show that hand rotation during X-ray imaging has an impact on
      the CAJSA measurements; thus avoiding acquisition of hand radiographs with a
      rotation error of more than 15 degrees can be recommended.

PMID- 21963810
TI  - Magnetic resonance image of the heart.

PMID- 21963811
TI  - An unfortunate teenager.

PMID- 21963812
TI  - Local autism strategy groups should be set up, NICE recommends.

PMID- 21963813
TI  - VisualDecisionLinc: a visual analytics approach for comparative effectiveness
      based clinical decision support in psychiatry.
AB  - Comparative Effectiveness Research (CER) is designed to provide research evidence
      on the effectiveness and risks of different therapeutic options on the basis of
      data compiled from subpopulations of patients with similar medical conditions.
      Electronic Health Record (EHR) system contain large volumes of patient data that
      could be used for CER, but the data contained in EHR system are typically
      accessible only in formats that are not conducive to rapid synthesis and
      interpretation of therapeutic outcomes. In the time-pressured clinical setting,
      clinicians faced with large amounts of patient data in formats that are not
      readily interpretable often feel 'information overload'. Decision support tools
      that enable rapid access at the point of care to aggregate data on the most
      effective therapeutic outcomes derived from CER would greatly aid the clinical
      decision-making process and individualize patient care. In this manuscript, we
      highlight the role that visual analytics can play in CER-based clinical decision
      support. We developed a 'VisualDecisionLinc' (VDL) tool prototype that uses
      visual analytics to provide summarized CER-derived data views to facilitate rapid
      interpretation of large amounts of data. We highlight the flexibility that visual
      analytics offers to gain an overview of therapeutic options and outcomes and if
      needed, to instantly customize the evidence to the needs of the patient or
      clinician. The VDL tool uses visual analytics to help the clinician evaluate and
      understand the effectiveness and risk of different therapeutic options for
      different subpopulations of patients.

PMID- 21963814
TI  - Reconstituting mammalian spermatogenesis using stem cells.

PMID- 21963815
TI  - Quantitative waveform measures of the electrocardiogram as continuous physiologic
      feedback during resuscitation with cardiopulmonary bypass.
AB  - BACKGROUND: There are few if any real-time physiologic measures that currently
      provide feedback during resuscitation from cardiac arrest. Such measures could be
      used to guide therapy not simply based on process guidelines but on the
      physiologic response of the patient from moment to moment. To this end, we
      applied an existing technology - quantitative waveform measures (QWMs) of the
      ventricular fibrillation (VF) electrocardiogram (ECG) - as a continuous measure
      of myocardial response to reperfusion with cardiopulmonary bypass (CPB) after
      prolonged cardiac arrest. METHODS: Sixteen domestic, mixed-breed swine were
      sedated, anesthetized and paralyzed. Mechanical ventilation with room air was
      provided. Large diameter bypass catheters were placed in the right external
      jugular vein and right femoral artery for cardiopulmonary bypass (CPB). VF was
      induced with a 3-s 100mA transthoracic shock and left untreated for 15, 20, 25,
      or 30min, followed by 10min of centrifugal pump CPB (Bard CPS). Continuous Lead
      II ECG was recorded with an electronic data acquisition system (Power Lab,
      ADInstruments). Four QWMs representing 4 signal characteristics of the VF ECG
      were calculated in 5-s windows throughout the course of untreated VF and
      resuscitation with CPB. RESULTS: Four animals were assigned to each VF duration
      group. QWM recovery was inversely correlated with untreated VF duration, and was
      drastically reduced above 20min of untreated VF. Return of spontaneous
      circulation (ROSC) was highly unlikely after 20min of untreated VF. CONCLUSION:
      QWMs of the VF ECG provided a real-time metric of myocardial electrophysiologic
      response to reperfusion with CPB. Resuscitation from greater than 20min of
      untreated cardiac arrest was unlikely. QWMs may be useful for titrating CPB
      duration before defibrillation and assessing CPR quality independently of process
      guidelines.

PMID- 21963816
TI  - Combination pharmacotherapy improves neurological outcome after asphyxial cardiac
      arrest.
AB  - AIM: To study the effects of the combination of adrenaline (epinephrine) and
      vasopressin compared to adrenaline alone on initial resuscitation success, 24h
      survival, and neurological outcome in a swine model of asphyxial cardiac arrest
      (CA). METHODS: This prospective randomized experimental study was conducted at a
      laboratory research department. Twenty female Landrace/Large-White pigs, 12-15
      weeks of age, were investigated. Asphyxial CA was induced by clamping of the
      endotracheal tube. After 4min of untreated CA, resuscitation was initiated by
      unclamping the endotracheal tube, mechanical ventilation, chest compressions and
      adrenaline (Group A) or a combination of adrenaline with vasopressin (Group A+V)
      administered intravenously. In case of restoration of spontaneous circulation
      (ROSC), the animals were monitored for 30min and then observed for 24h. RESULTS:
      Hemodynamic variables were measured at baseline during CPR and in the post
      resuscitation period. Statistically significant difference was observed in groups
      A and A+V regarding coronary perfusion pressure (CPP) during the first minute of
      CPR. In both groups, ROSC and survival rates were comparable (p=NS). Neurological
      deficit score (NDS) was significantly higher in the combination group 24h
      following CA (p<0.001). Brain histological damage score (HDS) was also better in
      the combination group (p<0.001). Total HDS and NDS showed a statistical
      significant correlation (p<0.001). CONCLUSIONS: In this porcine model of
      asphyxial CA, adrenaline alone as well as the combined administration of
      adrenaline and vasopressin resulted in similar ROSC and survival rates, but the
      combination of adrenaline and vasopressin resulted in improved neurological and
      cerebral histopathological outcomes.

PMID- 21963817
TI  - Neurologic recovery after therapeutic hypothermia in patients with post-cardiac
      arrest myoclonus.
AB  - Early myoclonus in comatose survivors of cardiac arrest, even when it is not
      myoclonic status epilepticus (MSE), is considered a sign of severe global brain
      ischemia and has been associated with high rates of mortality and poor neurologic
      outcomes. We report on three survivors of primary circulatory cardiac arrests who
      had good neurologic outcomes (two patients with a CPC score=1 and one patient
      with a CPC score=2) after mild therapeutic hypothermia, despite exhibiting
      massive myoclonus within the first 4h after return of spontaneous circulation.
      The concept that early myoclonus heralds a uniformly poor prognosis may need to
      be reconsidered in the era of post-cardiac arrest mild therapeutic hypothermia.

PMID- 21963818
TI  - The effectiveness of ERC advanced life support (ALS) provider courses for the
      retention of ALS knowledge.
AB  - PURPOSE: Out-of-hospital emergency physicians in Austria need mandatory emergency
      physician training, followed by biennial refresher courses. Currently, both
      standardized ERC advanced life support (ALS) provider courses and conventional
      refresher courses are offered. This study aimed to compare the retention of ALS
      knowledge of out-of-hospital emergency physicians depending on whether they had
      or had not participated in an ERC-ALS provider course since 2005. METHODS:
      Participants (n=807) from 19 refresher courses for out-of-hospital emergency
      physicians answered eight multiple-choice questions (MCQ) about ALS based on the
      2005 ERC guidelines. The pass score was 75% correct answers. A multivariate
      logistic regression analyzed differences in passing scores between those who had
      previously participated in an ERC-ALS provider course and those who had not. Age,
      gender, regularity of working as an out-of-hospital emergency physician and the
      self-reported number of real resuscitation efforts within the last 6months were
      entered as control variables. RESULTS: Out-of-hospital emergency physicians who
      had previously attended an ERC-ALS provider course had a significantly higher
      chance of passing the MCQ test (OR=1.60, p=0.015). Younger age (OR=0.95,
      p<0.001), regular work as an out-of-hospital emergency physician (OR=2.66,
      p<0.001) and a higher number of self-reported resuscitations within the last
      6months (OR=1.08, p=0.002) were also significant predictors of passing the test.
      CONCLUSION: Out-of-hospital emergency physicians that had attended an ERC-ALS
      provider course since 2005 had a higher retention of ALS knowledge compared to
      non-ERC-ALS course participants.

PMID- 21963819
TI  - Effects and limitations of an AED with audiovisual feedback for cardiopulmonary
      resuscitation.

PMID- 21963820
TI  - Identification of quantitative trait loci controlling gene expression during the
      innate immunity response of soybean.
AB  - Microbe-associated molecular pattern-triggered immunity (MTI) is an important
      component of the plant innate immunity response to invading pathogens. However,
      most of our knowledge of MTI comes from studies of model systems with relatively
      little work done with crop plants. In this work, we report on variation in both
      the microbe-associated molecular pattern-triggered oxidative burst and gene
      expression across four soybean (Glycine max) genotypes. Variation in MTI
      correlated with the level of pathogen resistance for each genotype. A
      quantitative trait locus analysis on these traits identified four loci that
      appeared to regulate gene expression during MTI in soybean. Likewise, we observed
      that both MTI variation and pathogen resistance were quantitatively inherited.
      The approach utilized in this study may have utility for identifying key
      resistance loci useful for developing improved soybean cultivars.

PMID- 21963821
TI  - Reinterventions for stent restenosis in patients treated for atherosclerotic
      mesenteric artery disease.
AB  - OBJECTIVE: Mesenteric artery angioplasty and stenting (MAS) has been plagued by
      high restenosis and reintervention rates. The purpose of this study was to review
      the outcomes of patients treated for mesenteric artery in-stent restenosis
      (MAISR). METHODS: The clinical data of 157 patients treated for chronic
      mesenteric ischemia with MAS of 170 vessels was entered into a prospective
      database (1998-2010). Fifty-seven patients (36%) developed MAISR after a mean
      follow-up of 29 months, defined by duplex ultrasound peak systolic velocity >330
      cm/s and angiographic stenosis >60%. We reviewed the clinical data, radiologic
      studies, and outcomes of patients who underwent reintervention for restenosis.
      End points were mortality and morbidity, patient survival, symptom recurrence,
      reintervention, and patency rates. RESULTS: There were 30 patients (25 female and
      five male; mean age, 69 +/- 14 years) treated with reintervention for MAISR.
      Twenty-four patients presented with recurrent symptoms (21 chronic, three acute),
      and six had asymptomatic preocclusive lesions. Twenty-six patients (87%)
      underwent redo endovascular revascularization (rER) with stent placement in 17
      (13 bare metal and four covered) or percutaneous transluminal angioplasty (PTA)
      in nine. The other four patients (13%) had open bypass, one for acute ischemia.
      There was one death (3%) in a patient treated with redo stenting for acute
      mesenteric ischemia. Seven patients (27%) treated by rER developed complications,
      including access site problems in four patients, and distal embolization with
      bowel ischemia, congestive heart failure and stent thrombosis in one each.
      Symptom improvement was noted in 22 of the 24 symptomatic patients (92%). After a
      mean follow-up of 29 +/- 12 months, 15 patients (50%) developed a second
      restenosis, and seven (23%) required other reintervention. Rates of symptom
      recurrence, restenosis, and reinterventions were 0/4, 0/4, and 0/4 for covered
      stents, 2/9, 3/9, and 2/9 for PTA, 5/13, 8/13, and 5/13 for bare metal stents,
      and 1/4, 4/4, and 0/4 for open bypass. For all patients, freedom from recurrent
      symptoms, restenosis, and reinterventions were 70% +/- 10%, 60% +/- 10% and 50%
      +/-10% at 2 years. For patients treated by rER, secondary patency rates were 72
      +/- 12 at the same interval. CONCLUSIONS: Nearly 40% of patients developed
      mesenteric artery in-stent restenosis, of which half required reintervention
      because of symptom recurrence or progression to an asymptomatic preocclusive
      lesion. Mesenteric reinterventions were associated with low mortality (3%), high
      complication rate (27%), and excellent symptom improvement (92%).

PMID- 21963822
TI  - Role of the AMP-activated protein kinase (AMPK) signaling pathway in the
      orexigenic effects of endogenous ghrelin.
AB  - Ghrelin, released from the stomach, stimulates food intake through activation of
      the ghrelin receptor (GHS-R) located on neuropeptide Y (NPY)/agouti-related
      peptide (AgRP) neurons in the hypothalamus. A role for the energy sensor AMP
      activated protein kinase (AMPK) and its downstream effector uncoupling protein 2
      (UCP2) in the stimulatory effect of exogenous ghrelin on NPY/AgRP expression and
      food intake has been suggested. This study aimed to investigate whether a rise in
      endogenous ghrelin levels is able to influence hypothalamic AMPK activity, pACC,
      UCP2 and NPY/AgRP expression through activation of GHS-R. An increase in
      endogenous ghrelin levels was established by fasting (24h) or by induction of
      streptozotocin(STZ)-diabetes (15 days) in GHS-R(+/+) and GHS-R(-/-) mice. GHS
      R(+/+) mice showed a significant increase in AgRP and NPY mRNA expression after
      fasting, which was not observed in GHS-R(-/-) mice. Fasting did not affect AMPK
      activity nor ACC phosphorylation in both genotypes and increased UCP2 mRNA
      expression. The hyperghrelinemia associated with STZ-induced diabetes was
      accompanied by an increased NPY and AgRP expression in GHS-R(+/+) but not in GHS
      R(-/-) mice. AMPK activity and UCP2 expression in GHS-R(+/+) mice after induction
      of diabetes were decreased to a similar extent in both genotypes. Exogenous
      ghrelin administration tended to decrease hypothalamic AMPK activity. In
      conclusion, an increase in endogenous ghrelin levels triggered by fasting or STZ
      induced diabetes stimulates the expression of AgRP and NPY via interaction with
      the GHS-R. The changes in AMPK activity, pACC and UCP2 occur independently from
      GHS-R suggesting that they do not play a major role in the orexigenic effect of
      endogenous ghrelin.

PMID- 21963823
TI  - Phlorofucofuroeckol A inhibits the LPS-stimulated iNOS and COX-2 expressions in
      macrophages via inhibition of NF-kappaB, Akt, and p38 MAPK.
AB  - We have recently reported that phlorofucofuroeckol A isolated from the edible
      brown algae Ecklonia stolonifera showed potential antioxidative and anti
      inflammatory properties in macrophage stimulated by LPS treatments. In this
      study, we further investigated the pharmacological characteristic of
      phlorofucofuroeckol A in regulations of inducible nitric oxide synthase (iNOS)
      and cyclooxygenase (COX)-2 through regulatory and signaling pathways using LPS
      treated RAW 264.7 cells. Treatment with 20 MUM of phlorofucofuroeckol A
      significantly decreased levels of iNOS and COX-2 mRNA induced by LPS stimulation.
      As results, levels of pro-inflammatory cytokines such as interleukin (IL)-1beta,
      IL-6 and tumor necrosis factor (TNF)-alpha were significantly reduced by
      treatments of phlorofucofuroeckol A in LPS-stimulated RAW 264.7 cells.
      Phlorofucofuroeckol A inhibited promoter activities of inflammatory-mediators
      (iNOS and COX-2) and transcriptional factors (nuclear factor-kappaB, NF-kappaB,
      and AP-1) in LPS-treated RAW 264.7 cells. Moreover, phlorofucofuroeckol A
      inhibited activation of Akt and p38 MAPK in LPS-treated RAW 264.7 cells. These
      results indicate that the phlorofucofuroeckol A regulates iNOS and COX-2
      expressions through the NF-kappaB-dependent transcriptional control associated
      with inhibition of multiple signaling proteins, suggesting potential candidates
      of phloroglucinol derivatives for treatments of inflammatory diseases.

PMID- 21963824
TI  - On the correlation between single-frequency impedance measurements and human skin
      permeability to water.
AB  - The objective of this study was to quantitatively compare measurements of
      tritiated water permeability with impedance determined at either 100 or 1000 Hz
      using an LCR databridge on the same pieces of skin. A previously published
      expression based on a simple circuit of a parallel resistor and constant phase
      element (CPE) was used to relate (RPARA) measured at different frequencies to the
      DC resistance (RskinA) and the steady-state skin permeability of tritiated water
      (kp). Using this analysis, kp and (RPARA) data from three laboratories were shown
      to be consistent with each other, and kp and (RskinA) estimated from (RPARA) were
      linearly correlated. Compared with urea and mannitol, which are known to permeate
      skin through a polar pathway, the value of kp for water was found to be about two
      times larger than expected for transport through only the polar pathway,
      suggesting an approximately equal contribution from the lipophilic pathway.
      Equations relating kp to (RPARA) and (RskinA) were used to compare on a
      consistent basis proposed tests for identifying and excluding damaged skin from
      chemical absorption studies. The criterion of 20 kOmega cm2 for (RskinA)
      corresponds to a tritiated water permeability of 3.2*10(-3) cm/h, which should
      exclude damaged skin without screening undamaged but higher permeability skin
      samples from study.

PMID- 21963825
TI  - A dynamical system analysis of the development of spontaneous lower extremity
      movements in newborn and young infants.
AB  - This study's aim was to evaluate the characteristics of newborn and young
      infants' spontaneous lower extremity movements by using dynamical systems
      analysis. Participants were 8 healthy full-term newborn infants (3 boys, 5 girls,
      mean birth weight and gestational age were 3070.6 g and 39 weeks). A tri-axial
      accelerometer measured limb movement acceleration in 3-dimensional space.
      Movement acceleration signals were recorded during 200 s from just below the
      ankle when the infant was in an active alert state and lying supine (sampling
      rate 200 Hz). Data were analyzed linearly and nonlinearly. As a result, the
      optimal embedding dimension showed more than 5 at all times. Time dependent
      changes started at 6 or 7, and over the next four months decreased to 5 and from
      6 months old, increased. The maximal Lyapnov exponent was positive for all
      segments. The mutual information is at its greatest range at 0 months. Between 3
      and 4 months the range in results is narrowest and lowest in value. The mean
      coefficient of correlation for the x-axis component was negative and y-axis
      component changed to a positive value between 1 month old and 4 months old.
      Nonlinear time series analysis suggested that newborn and young infants'
      spontaneous lower extremity movements are characterized by a nonlinear chaotic
      dynamics with 5 to 7 embedding dimensions. Developmental changes of an optimal
      embedding dimension showed a U-shaped phenomenon. In addition, the maximal
      Lyapnov exponents were positive for all segments (0.79-2.99). Infants'
      spontaneous movement involves chaotic dynamic systems that are capable of
      generating voluntary skill movements.

PMID- 21963826
TI  - Age-related changes and sex differences in postural control adaptability in
      children during periodic floor oscillation with eyes closed.
AB  - We investigated age-related changes and sex differences in adaptability of
      anticipatory postural control in children. Subjects comprised 449 children (4-12
      years old) and 109 young adults (18-29 years old). Subjects stood with eyes
      closed on a force-platform fixed to a floor oscillator. We conducted five trials
      of 1-minute oscillation (0.5 Hz frequency, 2.5 cm amplitude) in the
      anteroposterior direction. Postural steadiness was quantified as the mean speed
      of the center of pressure in the anteroposterior direction (CoPy). In young
      adults, CoPy speed decreased rapidly until the third trial for both sexes.
      Adaptability was evaluated by changes in steadiness. The adaptability of children
      was categorized as "good," "moderate," and "poor," compared with a standard
      variation of the mean CoPy speed regression line between the first and fifth
      trials in young adults. Results were as follows: (1) anticipatory postural
      control adaptability starts to develop from age 6 in boys and 5 in girls, and
      greatly improves at age 7-8 in boys and 6 in girls; (2) the adaptability of
      children at age 11-12 (74% of boys and 63% of girls were categorized as "good")
      has not yet reached the same level as for young adults; (3) the adaptability at
      age 11-12 for girls is temporarily disturbed due to early puberty.

PMID- 21963827
TI  - Effect of molecular hydrogen saturated alkaline electrolyzed water on disuse
      muscle atrophy in gastrocnemius muscle.
AB  - The objectives of this paper were to determine the level of oxidative stress in
      atrophied gastrocnemius, and to verify the effect of molecular hydrogen (H2)
      saturated alkaline electrolyzed water (HSW) on gastrocnemius atrophy by modifying
      the redox status, indicated by 8-hydroxy-2'-deoxyguanosine (8-OHdG),
      malondialdehyde (MDA), and superoxide dismutase (SOD)-like activity. Female
      Wistar rats were divided into four groups: (1) the control (CONT); (2) the
      Hindlimb unloading (HU, for 3 weeks) given purified normal water (HU-NW); (3) the
      HU given alkaline electrolyzed reduced water (HU-AEW); and (4) the HU given HSW
      (HU-HSW). We showed that 8-OHdG, but not MDA, significantly increased by 149% and
      145% in HU-NW and HU-AEW, respectively, when compared with CONT. In contrast,
      there was a trend toward suppression in 8-OHdG levels (increased by 95% compared
      with CONT) by treatment of HSW, though this effect was not prominent.
      Additionally, SOD-like activity significantly increased in both HU-NW (184%) and
      HU-AEW (199%) when compared with CONT. This result suggests the elevation of O2-.
      in the atrophied gastrocnemius. However, upregulation of SOD-like activity in the
      HU-HSW was increased by only 169% compared with CONT, though this difference is
      too small to detect statistical significance. HU led to 13% and 15% reduction of
      gastrocnemius wet weights in HU-NW and HU-AEW, respectively, compared with CONT.
      And the reduction of gastrocnemius wet weights in HU-HSW was attenuated by 7%
      compared with CONT. The gastrocnemius wet weights in the HU-HSW group were
      significantly greater than those in the HU-AEW, but not statistically significant
      with HU-NW. These results indicate that HU causes an increase in oxidative
      stress, but, in this experimental protocol, continuous consumption of HSW during
      HU does not demonstrate successful attenuation of oxidative stress and HU
      mediated gastrocnemius atrophy.

PMID- 21963828
TI  - Relationship between active cervical range of motion and flexion-relaxation ratio
      in asymptomatic computer workers.
AB  - A high prevalence and incidence of neck and shoulder pain is present in the
      working population, especially sedentary workers. Recent findings have indicated
      that the flexion-relaxation (FR) ratio in the cervical erector spinae (CES)
      muscles might be a significant criteria of neuromuscular impairment and function.
      Additionally, the active cervical range of motion (ROM) is frequently used for
      discriminating between individuals with pain and those who are asymptomatic. The
      purpose of the present study was to examine the relationship between the active
      cervical ROM and the FR ratio in a sample of regular visual display terminal
      (VDT) workers. In total, 20 asymptomatic male VDT workers were recruited. Active
      cervical ROM was measured by a cervical ROM (CROM) instrument. Surface
      electromyography (EMG) was used to collect myoelectrical signals from the CES
      muscles, and the FR ratio was calculated for statistical analysis. Pearson
      correlation coefficients were used to quantify the linear relationship between
      the active cervical ROM and the FR ratio. The values obtained for the FR ratio in
      the right CES muscles correlated significantly with the active cervical ROM
      measured in flexion (r=0.73, p<0.01), left lateral flexion (r=0.64, p<0.01), and
      left rotation (r=0.60, p<0.01). Flexion (r=0.74, p<0.01) and right lateral
      flexion (r=0.61, p<0.01) positively correlated with the left FR ratio. Extension
      and right rotation showed either a very weak or no correlation with the mean
      value of the right and left FR ratio. Our findings suggested that the cervical FR
      ratio had a positive correlation with cervical movements, and that changes of the
      activation patterns in CES demonstrated as cervical FR ratio are associated with
      reduction of the cervical range of motion including flexion and lateral flexion.
      In addition, muscular dysfunction of the CES could occur in regular computer
      workers prior to occurrence of pain; this means that the FR ratio could be used
      to evaluate the potential risk of neck discomfort in computer workers.

PMID- 21963829
TI  - Narcolepsy with hypocretin/orexin deficiency, infections and autoimmunity of the
      brain.
AB  - The loss of hypothalamic hypocretin/orexin (hcrt) producing neurons causes
      narcolepsy with cataplexy. An autoimmune basis for the disease has long been
      suspected and recent results have greatly strengthened this hypothesis.
      Narcolepsy with hcrt deficiency is now known to be associated with a Human
      Leukocyte Antigen (HLA) and T-cell receptor (TCR) polymorphisms, suggesting that
      an autoimmune process targets a single peptide unique to hcrt-cells via specific
      HLA-peptide-TCR interactions. Recent data have shown a robust seasonality of
      disease onset in children and associations with Streptococcus Pyogenes, and
      influenza A H1N1-infection and H1N1-vaccination, pointing towards processes such
      as molecular mimicry or bystander activation as crucial for disease development.
      We speculate that upper airway infections may be common precipitants of a whole
      host of CNS autoimmune complications including narcolepsy.

PMID- 21963830
TI  - Protic ionic liquids based on phosphonium cations: comparison with ammonium
      analogues.
AB  - Novel protic ionic liquids (PILs) based on a tributyl phosphonium cation have
      been synthesised and characterised, revealing that the phosphonium based ILs show
      high thermal stability, high ionic conductivity and facile proton reduction
      compared to the corresponding ammonium based ILs.

PMID- 21963831
TI  - Rheology of embryonic avian blood.
AB  - Shear stress, a mechanical force created by blood flow, is known to affect the
      developing cardiovascular system. Shear stress is a function of both shear rate
      and viscosity. While established techniques for measuring shear rate in embryos
      have been developed, the viscosity of embryonic blood has never been known but
      always assumed to be like adult blood. Blood is a non-Newtonian fluid, where the
      relationship between shear rate and shear stress is nonlinear. In this work, we
      analyzed the non-Newtonian behavior of embryonic chicken blood using a
      microviscometer and present the apparent viscosity at different hematocrits,
      different shear rates, and at different stages during development from 4 days
      (Hamburger-Hamilton stage 22) to 8 days (about Hamburger-Hamilton stage 34) of
      incubation. We chose the chicken embryo since it has become a common animal model
      for studying hemodynamics in the developing cardiovascular system. We found that
      the hematocrit increases with the stage of development. The viscosity of
      embryonic avian blood in all developmental stages studied was shear rate
      dependent and behaved in a non-Newtonian manner similar to that of adult blood.
      The range of shear rates and hematocrits at which non-Newtonian behavior was
      observed is, however, outside the physiological range for the larger vessels of
      the embryo. Under low shear stress conditions, the spherical nucleated blood
      cells that make up embryonic blood formed into small aggregates of cells. We
      found that the apparent blood viscosity decreases at a given hematocrit during
      embryonic development, not due to changes in protein composition of the plasma
      but possibly due to the changes in cellular composition of embryonic blood. This
      decrease in apparent viscosity was only visible at high hematocrit. At
      physiological values of hematocrit, embryonic blood viscosity did not change
      significantly with the stage of development.

PMID- 21963832
TI  - Angiotensin-converting enzyme 2 overexpression improves central nitric oxide
      mediated sympathetic outflow in chronic heart failure.
AB  - Angiotensin (ANG)-converting enzyme (ACE)2 in brain regions such as the
      paraventricular nucleus (PVN) controlling cardiovascular function may be involved
      in the regulation of sympathetic outflow in chronic heart failure (CHF). The
      purpose of this study was to determine if ACE2 plays a role in the central
      regulation of sympathetic outflow by regulating neuronal nitric oxide (NO)
      synthase (nNOS) in the PVN. We investigated ACE2 and nNOS expression within the
      PVN of rats with CHF. We then determined the effects of ACE2 gene transfer in the
      PVN on the contribution of NO-mediated sympathoinhibition in rats with CHF. The
      results showed that there were decreased expressions for ACE2, the ANG-(1-7)
      receptor, and nNOS within the PVN of rats with CHF. After the application of
      adenovirus vectors encoding ACE2 (AdACE2) into the PVN, the increased expression
      of ACE2 in the PVN was confirmed by Western blot analysis. AdACE2 transfection
      significantly increased nNOS protein levels (change of 50 +/- 5%) in the PVN of
      CHF rats. In anesthetized rats, AdACE2 treatment attenuated the responses of
      renal sympathetic nerve activity (RSNA), mean arterial pressure, and heart rate
      to the NOS inhibitor N-monomethyl-L-arginine in rats with CHF (RSNA: 28 +/- 3%
      vs. 16 +/- 3%, P < 0.05) compared with CHF + AdEGFP group. Furthermore, neuronal
      NG-108 cells incubated with increasing doses of AdACE2 showed a dose-dependent
      increase in nNOS protein expression (60% at the highest dose). Taken together,
      our data highlight the importance of increased expression and subsequent
      interaction of ACE2 and nNOS within the PVN, leading to a reduction in
      sympathetic outflow in the CHF condition.

PMID- 21963833
TI  - Intramuscular VEGF activates an SDF1-dependent progenitor cell cascade and an
      SDF1-independent muscle paracrine cascade for cardiac repair.
AB  - The skeletal muscle is endowed with an impressive ability to regenerate after
      injury, and this ability is coupled to paracrine production of many trophic
      factors possessing cardiovascular benefits. Taking advantage of this humoral
      capacity of the muscle, we recently demonstrated an extracardiac therapeutic
      regimen based on intramuscular delivery of VEGF-A(165) for repair of the failing
      hamster heart. This distal organ repair mechanism activates production from the
      injected hamstring of many trophic factors, among which stromal-derived factor-1
      (SDF1) prominently mobilized multi-lineage progenitor cells expressing CXCR4 and
      their recruitment to the heart. The mobilized bone marrow progenitor cells
      express the cardiac transcription factors myocyte enhancer factor 2c and GATA4
      and several major trophic factors, most notably IGF1 and VEGF. SDF1 blockade
      abrogated myocardial recruitment of CXCR4(+) and c-kit(+) progenitor cells with
      an insignificant effect on the hematopoietic progenitor lineage. The knockdown of
      cardiac progenitor cells led to deprivation of myocardial trophic factors,
      resulting in compromised cardiomyogenesis and angiogenesis. However, the VEGF
      injected hamstring continued to synthesize cardioprotective factors, contributing
      to moderate myocardial tissue viability and function even in the presence of SDF1
      blockade. These findings thus uncover two distinct but synergistic cardiac
      therapeutic mechanisms activated by intramuscular VEGF. Whereas the SDF1/CXCR4
      axis activates the progenitor cell cascade and its trophic support of
      cardiomyogenesis intramuscularly, VEGF amplifies the skeletal muscle paracrine
      cascade capable of directly promoting myocardial survival independent of SDF1.
      Given that recent clinical trials of cardiac repair based on the use of marrow
      mobilizing agents have been disappointing, the proposed dual therapeutic modality
      warrants further investigation.

PMID- 21963834
TI  - Sex differences in carotid baroreflex control of arterial blood pressure in
      humans: relative contribution of cardiac output and total vascular conductance.
AB  - It is presently unknown whether there are sex differences in the magnitude of
      blood pressure (BP) responses to baroreceptor perturbation or if the relative
      contribution of cardiac output (CO) and total vascular conductance (TVC) to
      baroreflex-mediated changes in BP differs in young women and men. Since
      sympathetic vasoconstrictor tone is attenuated in women, we hypothesized that
      carotid baroreflex-mediated BP responses would be attenuated in women by virtue
      of a blunted vascular response (i.e., an attenuated TVC response). BP, heart rate
      (HR), and stroke volume were continuously recorded during the application of 5-s
      pulses of neck pressure (NP; carotid hypotension) and neck suction (NS; carotid
      hypertension) ranging from +40 to -80 Torr in women (n = 20, 21 +/- 0.5 yr) and
      men (n = 20, 21 +/- 0.4 yr). CO and TVC were calculated on a beat-to-beat basis.
      Women demonstrated greater depressor responses to NS (e.g., -60 Torr, -17 +/-
      1%baseline in women vs. -11 +/- 1%baseline in men, P < 0.05), which were driven
      by augmented decreases in HR that, in turn, contributed to larger reductions in
      CO (-60 Torr, -15 +/- 2%baseline in women vs. -6 +/- 2%baseline in men, P <
      0.05). In contrast, pressor responses to NP were similar in women and men (e.g.,
      +40 Torr, +14 +/- 2%baseline in women vs. +10 +/- 1%baseline in men, P > 0.05),
      with TVC being the primary mediating factor in both groups. Our findings indicate
      that sex differences in the baroreflex control of BP are evident during carotid
      hypertension but not carotid hypotension. Furthermore, in contrast to our
      hypothesis, young women exhibited greater BP responses to carotid hypertension by
      virtue of a greater cardiac responsiveness.

PMID- 21963835
TI  - Cardiac regeneration therapy: connections to cardiac physiology.
AB  - Without heart transplantation, a large number of patients with failing hearts
      worldwide face poor outcomes. By means of cardiomyocyte regeneration, cardiac
      regeneration therapy is emerging with great promise as a means for restoring loss
      of cardiac function. However, the limited success of clinical trials using bone
      marrow-derived cells and myoblasts with heterogeneous constituents, transplanted
      at a wide range of cell doses, has led to disagreement on the efficacy of cell
      therapy. It is therefore essential to reevaluate the evidence for the efficacy of
      cell-based cardiac regeneration therapy, focusing on targets, materials, and
      methodologies. Meanwhile, the revolutionary innovation of cardiac regeneration
      therapy is sorely needed to help the millions of people who suffer heart failure
      from acquired loss of cardiomyocytes. Cardiac regeneration has been used only in
      limited species or as a developing process in the rodent heart; now, the
      possibility of cardiomyocyte turnover in the human heart is being revisited. In
      the pursuit of this concept, the use of cardiac stem/progenitor stem cells in the
      cardiac niche must be focused to usher in a second era of cardiac regeneration
      therapy for the severely injured heart. In addition, tissue engineering and
      cellular reprogramming will advance the next era of treatment that will enable
      current cell-based therapy to progress to "real" cardiac regeneration therapy.
      Although many barriers remain, the prevention of refractory heart failure through
      cardiac regeneration is now becoming a realistic possibility.

PMID- 21963836
TI  - Renin released from mast cells activated by circulating MCP-1 initiates the
      microvascular phase of the systemic inflammation of alveolar hypoxia.
AB  - Reduced alveolar Po(2) in rats produces a rapid systemic inflammation
      characterized by reactive O(2) species generation, mast cell (MC) degranulation,
      leukocyte-endothelial interactions, and increased vascular permeability. The
      inflammation is not initiated by the low systemic Po(2) but rather by the release
      of monocyte chemoattractant protein-1 (MCP-1) from alveolar macrophages (AMO)
      activated by alveolar hypoxia. Circulating AMO-borne MCP-1 induces MC
      degranulation, which activates the local renin-angiotensin system (RAS) and
      mediates the microvascular inflammation. This study was directed to determine the
      mechanism of RAS activation by MCP-1-induced MC degranulation. Experiments in
      isolated rat peritoneal MCs showed the following: 1) Western blots and
      immunocytochemistry demonstrated the presence of renin and angiotensin-converting
      enzyme (ACE) in MCs and their release upon degranulation; 2) MCP-1-induced
      degranulation of MCs incubated in plasma produced an increase in angiotensin II
      (ANG II) concentration; and 3) this increase was inhibited completely by the
      following agents: the MCP-1 receptor antagonist RS-102895, the specific rat renin
      inhibitor WFML, or the ACE inhibitor captopril administered separately. Captopril
      also inhibited ANG II generation by MCs incubated in culture medium plus ANG I.
      The results show that peritoneal MCs contain active renin, which activates the
      RAS upon degranulation, and that peritoneal MCs are a source of ACE and suggest
      that conversion of ANG I to ANG II is mediated predominantly by ACE. This study
      provides novel evidence of the presence of active renin in rat peritoneal MCs and
      helps explain the mechanism of activation of the RAS during alveolar hypoxia.

PMID- 21963837
TI  - A selective phosphodiesterase 3 inhibitor rescues low PO2-induced ATP release
      from erythrocytes of humans with type 2 diabetes: implication for vascular
      control.
AB  - Erythrocytes, via release of ATP in areas of low oxygen (O(2)) tension, are
      components of a regulatory system for the distribution of perfusion in skeletal
      muscle ensuring optimal O(2) delivery to meet tissue needs. In type 2 diabetes
      (DM2), there are defects in O(2) supply to muscle as well as a failure of
      erythrocytes to release ATP. The goal of this study was to ascertain if a
      phosphodiesterase 3 (PDE3) inhibitor, cilostazol, would rescue low O(2)-induced
      ATP release from DM2 erythrocytes and, thereby, enable these cells to dilate
      isolated erythrocyte-perfused skeletal muscle arterioles exposed to decreased
      extraluminal O(2). Erythrocytes were obtained from healthy humans (HH; n = 12)
      and humans with DM2 (n = 17). We determined that 1) PDE3B is similarly expressed
      in both groups, 2) mastoparan 7 (G(i) activation) stimulates increases in cAMP in
      HH but not in DM2 erythrocytes, and 3) pretreatment of DM2 erythrocytes with
      cilostazol resulted in mastoparan 7-induced increases in cAMP not different from
      those in HH cells. Most importantly, cilostazol restored the ability of DM2
      erythrocytes to release ATP in response to low O(2). In contrast with perfusion
      with HH erythrocytes, isolated hamster retractor muscle arterioles perfused with
      DM2 erythrocytes constricted in response to low extraluminal PO(2). However, in
      the presence of cilostazol (100 MUM), DM2 erythrocytes induced vessel dilation
      not different from that seen with HH erythrocytes. Thus rescue of low O(2)
      induced ATP release from DM2 erythrocytes by cilostazol restored the ability of
      erythrocytes to participate in the regulation of perfusion distribution in
      skeletal muscle.

PMID- 21963838
TI  - Differential effects of eNOS uncoupling on conduit and small arteries in GTP
      cyclohydrolase I-deficient hph-1 mice.
AB  - In the present study, we used the hph-1 mouse, which displays GTP-cyclohydrolase
      I (GTPCH I) deficiency, to test the hypothesis that loss of tetrahydrobiopterin
      (BH(4)) in conduit and small arteries activates compensatory mechanisms designed
      to protect vascular wall from oxidative stress induced by uncoupling of
      endothelial nitric oxide synthase (eNOS). Both GTPCH I activity and BH(4) levels
      were reduced in the aortas and small mesenteric arteries of hph-1 mice. However,
      the BH(4)-to-7,8-dihydrobiopterin ratio was significantly reduced only in hph-1
      aortas. Furthermore, superoxide anion and 3-nitrotyrosine production were
      significantly enhanced in aortas but not in small mesenteric arteries of hph-1
      mice. In contrast to the aorta, protein expression of copper- and zinc-containing
      superoxide dismutase (CuZnSOD) was significantly increased in small mesenteric
      arteries of hph-1 mice. Protein expression of catalase was increased in both
      aortas and small mesenteric arteries of hph-1 mice. Further analysis of
      endothelial nitric oxide synthase (eNOS)/cyclic guanosine monophosphate (cGMP)
      signaling demonstrated that protein expression of phosphorylated Ser(1177)-eNOS
      as well as basal cGMP levels and hydrogen peroxide was increased in hph-1 aortas.
      Increased production of hydrogen peroxide in hph-1 mice aortas appears to be the
      most likely mechanism responsible for phosphorylation of eNOS and elevation of
      cGMP. In contrast, upregulation of CuZnSOD and catalase in resistance arteries is
      sufficient to protect vascular tissue from increased production of reactive
      oxygen species generated by uncoupling of eNOS. The results of our study suggest
      that anatomical origin determines the ability of vessel wall to cope with
      oxidative stress induced by uncoupling of eNOS.

PMID- 21963839
TI  - Human microvascular dysfunction and apoptotic injury induced by AL amyloidosis
      light chain proteins.
AB  - Light chain amyloidosis (AL) involves overproduction of amyloidogenic light chain
      proteins (LC) leading to heart failure, yet the mechanisms underlying tissue
      toxicity remain unknown. We hypothesized that LC induces endothelial dysfunction
      in non-AL human microvasculature and apoptotic injury in human coronary artery
      endothelial cells (HCAECs). Adipose arterioles (n = 34, 50 +/- 3 yr) and atrial
      coronary arterioles (n = 19, 68 +/- 2 yr) from non-AL subjects were cannulated.
      Adipose arteriole dilator responses to acetylcholine/papaverine were measured at
      baseline and 1 h exposure to LC (20 MUg/ml) from biopsy-proven AL subjects (57 +/
      11 yr) without and with antioxidant cotreatment. Coronary arteriole dilation to
      bradykinin/papaverine was measured post-LC exposure. HCAECs were exposed to 1 or
      24 h of LC. LC reduced dilation to acetylcholine (10(-4) M: 41.6 +/- 7 vs. 85.8
      +/- 2.2% control, P < 0.001) and papaverine (81.4 +/- 4.6 vs. 94.8 +/- 1.3%
      control, P < 0.01) in adipose arterioles and to bradykinin (10(-6) M: 68.6 +/-
      6.2 vs. 90.9 +/- 1.6% control, P < 0.001) but not papaverine in coronary
      arterioles. There was an increase in superoxide and peroxynitrite in arterioles
      treated with LC. Adipose arteriole dilation was restored by cotreatment with
      polyethylene glycol-superoxide dismutase and tetrahydrobiopterin but only
      partially restored by mitoquinone (mitochondria-targeted antioxidant) and gp91ds
      tat (NADPH oxidase inhibitor). HCAECs exposed to LC showed reduced NO and
      increased superoxide, peroxynitrite, annexin-V, and propidium iodide compared
      with control. Brief exposure to physiological amounts of LC induced endothelial
      dysfunction in human adipose and coronary arterioles and increased apoptotic
      injury in coronary artery endothelial cells likely as a result of oxidative
      stress, reduced NO bioavailability, and peroxynitrite production. Microvascular
      dysfunction and injury is a novel mechanism underlying AL pathobiology and is a
      potential target for therapy.

PMID- 21963840
TI  - The alpha-linolenic acid content of flaxseed can prevent the atherogenic effects
      of dietary trans fat.
AB  - Dietary intake of industrially hydrogenated trans fatty acids (TFA) has been
      associated with coronary heart disease. Dietary flaxseed can inhibit
      atherosclerosis induced by dietary cholesterol. The aim of this study was to
      determine whether supplementing the diet with flaxseed could protect against
      atherosclerosis induced by a diet enriched in TFA. Low-density lipoprotein
      receptor-deficient (LDLr(-/-)) mice were fed 1 of 14 experimental diets for 14 wk
      containing one of two fat sources [regular (pork/soy) or trans fat] at two
      concentrations (4 or 8%) and supplemented with or without dietary cholesterol
      (2%), whole ground flaxseed, or one of the components of flaxseed [alpha
      linolenic acid (ALA), defatted fiber, or lignan]. Adding flaxseed to the diet
      partially mitigated the rise in circulating cholesterol levels induced by the
      cholesterol-enriched diet. Atherosclerosis was stimulated by TFA and/or
      cholesterol. Including milled flaxseed to an atherogenic diet significantly
      reduced atherosclerosis compared with the groups that consumed cholesterol and/or
      TFA. ALA was the only component within flaxseed that could inhibit the
      atherogenic action of cholesterol and/or TFA on its own. Dietary flaxseed
      protects against atherosclerotic development induced by TFA and cholesterol
      feeding through its content of ALA.

PMID- 21963841
TI  - Double rotation of the opening (closing) elytra in beetles (Coleoptera).
AB  - Transient movements of the elytra (opening and closing) were filmed in beetles
      tethered from below. A total of 39 specimens of 18 species representing 11
      families were examined. Bright markers glued to the elytra were traced frame by
      frame. Body-fixed 3D traces of apical and shoulder markers were reconstructed.
      Shapes of traces reflected different steps of elytral movement and different
      types of flight. Flat circular arcs were fitted to scattered traces using the
      least square method. The rotation axis of the apical marker was always directed
      at the contralateral side. The trace of the shoulder marker was, as a rule, non
      parallel to the apical trace. Usually, the shoulder marker on the costal edge of
      the elytron uniformly supinated in the course of adduction of the apical marker.
      Traces of opening and closing coincided, hence the double rotation of the elytron
      had one degree of freedom. The elytron to body articulation in beetles is,
      presumably, a spherical mechanism with two separate but linked drives for a broad
      swing during opening (closing).

PMID- 21963842
TI  - Hepatocellular carcinoma enters the sequencing era.

PMID- 21963843
TI  - MicroRNA-mediated breast cancer metastasis: from primary site to distant organs.
AB  - The recent upsurge of interest in microRNA (miRNA) is partly attributed to the
      discovery of the novel roles of miRNAs in many physiological and pathological
      processes, including tumor development. Research on breast cancer metastasis has
      also focused on the concept of miRNA, which can act either as promoters or as
      suppressors of metastases. This review will focus on a series of recent studies
      that demonstrate the involvement of miRNAs in breast cancer metastasis and will
      briefly describe various pathways of miRNA-regulated metastasis. Finally, future
      prospects will be discussed for the potential role of miRNAs as predictive
      markers and therapeutic agents for patients with breast cancer metastases.

PMID- 21963845
TI  - Attenuation of the beta-catenin/TCF4 complex in colorectal cancer cells induces
      several growth-suppressive microRNAs that target cancer promoting genes.
AB  - Aberrant activation of the Wnt signaling pathway is causally involved in the
      formation of most colorectal cancers (CRCs). Although detailed knowledge exists
      regarding Wnt-regulated protein-coding genes, much less is known about the
      possible involvement of non-coding RNAs. Here we used TaqMan Array MicroRNA
      Cards, capable of detecting 664 unique human microRNAs (miRNAs), to describe
      changes of the miRNA transcriptome following disruption of beta-catenin/TCF4
      activity in DLD1 CRC cells. Most miRNAs appeared to respond independent of host
      gene regulation and proximal TCF4 chromatin occupancy as inferred from expression
      microarray and ChIP-chip data. A module of miRNAs induced by abrogated Wnt
      signaling in vitro was downregulated in two independent series of human primary
      CRCs (n=76) relative to normal adjacent mucosa (n=34). Several of these miRNAs
      (miR-145, miR-126, miR-30e-3p and miR-139-5p) markedly inhibited CRC cell growth
      in vitro when ectopically expressed. By using an integrative approach of
      proteomics and expression microarrays, we found numerous mRNAs and proteins to be
      affected by ectopic miR-30e-3p levels. This included HELZ and PIK3C2A that were
      directly repressed by several miRNA binding sites as confirmed by luciferase
      reporter assays in combination with mutational analyses. Finally, small
      interfering RNA-mediated downregulation of PIK3C2A, but not HELZ, was sufficient
      on its own to restrict CRC cell growth. Collectively, our study demonstrates that
      multiple miRNAs are upregulated as a consequence of forced attenuation of Wnt
      signaling in CRC cells, and some of these miRNAs inhibit cell growth with
      concomitant suppression of several growth-stimulatory cancer-related genes.

PMID- 21963844
TI  - Four proteins governing overangiogenic endothelial cell phenotype in patients
      with multiple myeloma are plausible therapeutic targets.
AB  - Bone marrow (BM) angiogenesis has an important role in the initiation and
      progression of multiple myeloma (MM). We looked at novel mechanisms of vessel
      formation in patients with MM through a comparative proteomic analysis between BM
      endothelial cells (ECs) of patients with active MM (MMECs) and ECs of patients
      with monoclonal gammopathy of undetermined significance (MGECs) and of subjects
      with benign anemia (normal ECs). Four proteins were found overexpressed in MMECs:
      filamin A, vimentin, alpha-crystallin B and 14-3-3zeta/delta protein, not yet
      linked to overangiogenic phenotype. These proteins gave a typical distribution in
      the BM of MM patients and in MMECs versus MGECs, plausibly according to a
      different functional state. Their expression was enhanced by vascular endothelial
      growth factor, fibroblast growth factor 2, hepatocyte growth factor and MM plasma
      cell conditioned medium in step with enhancement of MMEC angiogenesis. Their
      silencing RNA knockdown affected critical MMEC angiogenesis-related functions,
      such as spreading, migration and tubular morphogenesis. A gradual stabilization
      of 14-3-3zeta/delta protein was observed, with transition from normal ECs to
      MGECs and MMECs that may be a critical step for the angiogenic switch in MMECs
      and maintenance of the cell overangiogenic phenotype. These proteins were
      substantially impacted by anti-MM drugs, such as bortezomib, lenalidomide and
      panobinostat. Results suggest that these four proteins could be new targets for
      the antiangiogenic management of MM patients.

PMID- 21963846
TI  - Tissue transglutaminase links TGF-beta, epithelial to mesenchymal transition and
      a stem cell phenotype in ovarian cancer.
AB  - Tissue transglutaminase (TG2), an enzyme involved in cell proliferation,
      differentiation and apoptosis is overexpressed in ovarian carcinomas, where it
      modulates epithelial-to-mesenchymal transition (EMT) and promotes metastasis. Its
      regulation in ovarian cancer (OC) remains unexplored. Here, we show that
      transforming growth factor (TGF)-beta, a cytokine involved in tumor dissemination
      is abundantly secreted in the OC microenvironment and induces TG2 expression and
      enzymatic activity. This is mediated at transcriptional level by SMADs and by TGF
      beta-activated kinase 1-mediated activation of the nuclear factor-kappaB complex.
      TGF-beta-stimulated OC cells aggregate as spheroids, which enable peritoneal
      dissemination. We show that TGF-beta-induced TG2 regulates EMT, formation of
      spheroids and OC metastasis. TG2 knock-down in OC cells decreases the number of
      cells harboring a cancer stem cell phenotype (CD44+/CD117+). Furthermore,
      CD44+/CD117+ cells isolated from human ovarian tumors express high levels of TG2.
      In summary, TGF-beta-induced TG2 enhances ovarian tumor metastasis by inducing
      EMT and a cancer stem cell phenotype.

PMID- 21963847
TI  - Tumor suppressors govern insulin-like growth factor signaling pathways:
      implications in metabolism and cancer.
AB  - The insulin-like growth factor (IGF) axis mediates growth, differentiation and
      developmental processes, and is also involved in control of metabolic activities.
      Deregulation of IGF axis expression and action is linked to a number of
      pathologies, ranging from metabolic disorders to growth deficits and cancer
      development. Activation of the IGF signaling pathway is a crucial prerequisite
      for malignant transformation. In addition, overexpression of the IGF-1 receptor
      (IGF-1R) constitutes a typical hallmark of most types of cancer. A series of
      tumor suppressors have been identified whose mechanisms of action involve
      transcriptional suppression of the IGF-1R gene. These tumor suppressors include
      the p53/p63/p73 family, breast cancer gene-1, von-Hippel Lindau protein, Wilms'
      tumor-1 and others. Comprehensive analyses have identified a complex
      bidirectional interplay between the IGF and tumor-suppressor signaling pathways.
      These interactions are of major importance in terms of cancer development and may
      also predict responsiveness to IGF-1R-targeted therapies. Furthermore, the
      insulin/IGF system has a pivotal role in the regulation of cancer cell
      metabolism. Deregulation of IGF axis components by mutated tumor-suppressor
      proteins may lead to metabolic perturbations, with ensuing pathological
      consequences.

PMID- 21963848
TI  - Myc, Aurora Kinase A, and mutant p53(R172H) co-operate in a mouse model of
      metastatic skin carcinoma.
AB  - Clinical observations, as well as data obtained from the analysis of genetically
      engineered mouse models, firmly established the gain-of-function (GOF) properties
      of certain p53 mutations. However, little is known about the underlying
      mechanisms. We have used two independent microarray platforms to perform a
      comprehensive and global analysis of tumors arising in a model of metastatic skin
      cancer progression, which compares the consequences of a GOF p53(R172H) mutant vs
      p53 deficiency. DNA profiling revealed a higher level of genomic instability in
      GOF vs loss-of-function (LOF) p53 squamous cell carcinomas (SCCs). Moreover, GOF
      p53 SCCs showed preferential amplification of Myc with a corresponding increase
      in its expression and deregulation of Aurora Kinase A. Fluorescent in situ
      hybridization confirmed amplification of Myc in primary GOF p53 SCCs and its
      retention in metastatic tumors. We also identified by RNA profiling distinct gene
      expression profiles in GOF p53 tumors, which included enriched integrin and Rho
      signaling, independent of tumor stage. Thus, the progression of GOF p53
      papillomas to carcinoma was marked by the acquisition of epithelial-to
      mesenchymal transition and metastatic signatures. In contrast, LOF p53 tumors
      showed enrichment of genes associated with cancer proliferation and chromosomal
      instability. Collectively, these observations suggest that genomic instability
      has a prominent role in the early stages of GOF p53 tumor progression (that is,
      papillomas), whereas it is implicated at a later stage in LOF p53 tumors (that
      is, SCCs). This model will allow us to identify specific targets in mutant p53
      SCCs, which may lead to the development of new therapeutic agents for the
      treatment of metastatic SCCs.

PMID- 21963849
TI  - NF-kappaB inducing kinase (NIK) modulates melanoma tumorigenesis by regulating
      expression of pro-survival factors through the beta-catenin pathway.
AB  - Nuclear factor-kappaB (NF-kappaB) inducing kinase (NIK) is a MAP3K that regulates
      the activation of NF-kappaB. NIK is often highly expressed in tumor cells,
      including melanoma, but the significance of this in melanoma progression has been
      unclear. Tissue microarray analysis of NIK expression reveals that dysplastic
      nevi (n=22), primary (n=15) and metastatic melanoma (n=13) lesions showed a
      statistically significant elevation in NIK expression when compared with benign
      nevi (n=30). Moreover, when short hairpin RNA techniques were used to knock-down
      NIK, the resultant NIK-depleted melanoma cell lines exhibited decreased
      proliferation, increased apoptosis, delayed cell cycle progression and reduced
      tumor growth in a mouse xenograft model. As expected, when NIK was depleted there
      was decreased activation of the non-canonical NF-kappaB pathway, whereas
      canonical NF-kappaB activation remained intact. NIK depletion also resulted in
      reduced expression of genes that contribute to tumor growth, including CXCR4, c
      MYC and c-MET, and pro-survival factors such as BCL2 and survivin. These changes
      in gene expression are not fully explained by the attenuation of the non
      canonical NF-kappaB pathway. Shown here for the first time is the demonstration
      that NIK modulates beta-catenin-mediated transcription to promote expression of
      survivin. NIK-depleted melanoma cells exhibited downregulation of survivin as
      well as other beta-catenin regulated genes including c-MYC, c-MET and CCND2.
      These data indicate that NIK mediates both beta-catenin and NF-kappaB regulated
      transcription to modulate melanoma survival and growth. Thus, NIK may be a
      promising therapeutic target for melanoma.

PMID- 21963850
TI  - EGFR-dependent pancreatic carcinoma cell metastasis through Rap1 activation.
AB  - Tyrosine kinase receptors have an essential role in various aspects of tumor
      progression. In particular, epidermal growth factor receptor (EGFR) and its
      ligands have been implicated in the growth and dissemination of a wide array of
      human carcinomas. Here, we describe an EGFR-mediated signaling pathway that
      regulates human pancreatic carcinoma cell invasion and metastasis, yet does not
      influence the growth of primary tumors. In fact, ligation/activation of EGFR
      induces Src-dependent phosphorylation of two critical tyrosine residues of
      p130CAS, leading to the assembly of a Crk-associated substrate (CAS)/Nck1 complex
      that promotes Ras-associated protein-1 (Rap1) signaling. Importantly, GTP loading
      of Rap1 is specifically required for pancreatic carcinoma cell migration on
      vitronectin but not on collagen. Furthermore, Rap1 activation is required for
      EGFR-mediated metastasis in vivo without impacting primary tumor growth. These
      findings identify a molecular pathway that promotes the invasive/metastatic
      properties of human pancreatic carcinomas driven by EGFR.

PMID- 21963852
TI  - Caspase-3 and prostaglandins signal for tumor regrowth in cancer therapy.
AB  - Chemo- and radio-therapeutic regimens frequently kill cancer cells by inducing
      apoptosis, a cell-death subroutine that involves the activation of a particular
      class of proteases called caspases. In a recent issue of Nature Medicine, Huang
      et al. (2011) show that caspase activation in dying tumor cells causes the
      release of soluble lipid messengers, notably prostaglandin E(2), that stimulate
      tumor cell proliferation. In this short review, we will discuss the clinical and
      therapeutic implications of these findings.

PMID- 21963851
TI  - A role for collagen XXIII in cancer cell adhesion, anchorage-independence and
      metastasis.
AB  - Collagen XXIII is a transmembrane collagen previously shown to be upregulated in
      metastatic prostate cancer that has been used as a tissue and fluid biomarker for
      non-small cell lung cancer and prostate cancer. To determine whether collagen
      XXIII facilitates cancer cell metastasis in vivo and to establish a function for
      collagen XXIII in cancer progression, collagen XXIII knockdown cells were
      examined for alterations in in vivo metastasis as well as in vitro cell adhesion.
      In experimental and spontaneous xenograft models of metastasis, H460 cells
      expressing collagen XXIII shRNA formed fewer lung metastases than control cells.
      Loss of collagen XXIII in H460 cells also impaired cell adhesion, anchorage
      independent growth and cell seeding to the lung, but did not affect cell
      proliferation. Corroborating a role for collagen XXIII in cell adhesion,
      overexpression of collagen XXIII in H1299 cells, which do not express endogenous
      collagen XXIII, enhanced cell adhesion. Consequent reduction in OB-cadherin,
      alpha-catenin, gamma-catenin, beta-catenin, vimentin and galectin-3 protein
      expression was also observed in response to loss of collagen XXIII. This study
      suggests a potential role for collagen XXIII in mediating metastasis by
      facilitating cell-cell and cell-matrix adhesion as well as anchorage-independent
      cell growth.

PMID- 21963855
TI  - Checkpoint control and cancer.
AB  - DNA-damaging therapies represent the most frequently used non-surgical anticancer
      strategies in the treatment of human tumors. These therapies can kill tumor
      cells, but at the same time they can be particularly damaging and mutagenic to
      healthy tissues. The efficacy of DNA-damaging treatments can be improved if tumor
      cell death is selectively enhanced, and the recent application of poly-(ADP
      ribose) polymerase inhibitors in BRCA1/2-deficient tumors is a successful example
      of this. DNA damage is known to trigger cell-cycle arrest through activation of
      DNA-damage checkpoints. This arrest can be reversed once the damage has been
      repaired, but irreparable damage can promote apoptosis or senescence.
      Alternatively, cells can reenter the cell cycle before repair has been completed,
      giving rise to mutations. In this review we discuss the mechanisms involved in
      the activation and inactivation of DNA-damage checkpoints, and how the transition
      from arrest and cell-cycle re-entry is controlled. In addition, we discuss recent
      attempts to target the checkpoint in anticancer strategies.

PMID- 21963853
TI  - BAG-1 interacts with the p50-p50 homodimeric NF-kappaB complex: implications for
      colorectal carcinogenesis.
AB  - Understanding the mechanisms that promote aberrant tumour cell survival is
      critical for the determination of novel strategies to combat colorectal cancer
      (CRC). We have recently shown that the anti-apoptotic protein BAG-1, highly
      expressed in pre-malignant and CRC tissue, can potentiate cell survival through
      regulating NF-kappaB transcriptional activity. In this study, we identify a novel
      complex between BAG-1 and the p50-p50 NF-kappaB homodimers, implicating BAG-1 as
      a co-regulator of an atypical NF-kappaB pathway. Importantly, the BAG-1-p50
      complex was detected at gene regulatory sequences including the epidermal growth
      factor receptor (EGFR) and COX-2 (PTGS2) genes. Suppression of BAG-1 expression
      using small interfering RNA was shown to increase EGFR and suppress COX-2
      expression in CRC cells. Furthermore, mouse embryonic fibroblasts derived from
      the NF-kappaB1 (p105/p50) knock-out mouse were used to demonstrate that p50
      expression was required for BAG-1 to suppress EGFR expression. This was shown to
      be functionally relevant as attenuation of BAG-1 expression increased ligand
      activated phosphorylation of EGFR in CRC cells. In summary, this paper identifies
      a novel role for BAG-1 in modulating gene expression through interaction with the
      p50-p50 NF-kappaB complexes. Data presented led us to propose that BAG-1 can act
      as a selective regulator of p50-p50 NF-kappaB responsive genes in colorectal
      tumour cells, potentially important for the promotion of cell survival in the
      context of the fluctuating tumour microenvironment. As BAG-1 expression is
      increased in the developing adenoma through to metastatic lesions, understanding
      the function of the BAG-1-p50 NF-kappaB complexes may aid in identifying
      strategies for both the prevention and treatment of CRC.

PMID- 21963854
TI  - The HPV E6 oncoprotein targets histone methyltransferases for modulating specific
      gene transcription.
AB  - Expression of viral proteins causes important epigenetic changes leading to
      abnormal cell growth. Whether viral proteins directly target histone
      methyltransferases (HMTs), a key family enzyme for epigenetic regulation, and
      modulate their enzymatic activities remains elusive. Here we show that the E6
      proteins of both low-risk and high-risk human papillomavirus (HPV) interact with
      three coactivator HMTs, CARM1, PRMT1 and SET7, and downregulate their enzymatic
      activities in vitro and in HPV-transformed HeLa cells. Furthermore, these three
      HMTs are required for E6 to attenuate p53 transactivation function.
      Mechanistically, E6 hampers CARM1- and PRMT1-catalyzed histone methylation at p53
      responsive promoters, and suppresses the binding of p53 to chromatinized DNA
      independently of E6-mediated p53 degradation. p53 pre-methylated at lysine-372
      (p53K372 mono-methylation) by SET7 protects p53 from E6-induced degradation.
      Consistently, E6 downregulates p53K372 mono-methylation and thus reduces p53
      protein stability. As a result of the E6-mediated inhibition of HMT activity,
      expression of p53 downstream genes is suppressed. Together, our results not only
      reveal a clever approach for the virus to interfere with p53 function, but also
      demonstrate the modulation of HMT activity as a novel mechanism of epigenetic
      regulation by a viral oncoprotein.

PMID- 21963856
TI  - A prophenoloxidase from Artemia sinica: cDNA cloning, expression and activity
      analysis during early development.
AB  - To understand the defense mechanisms of Crustacean animals, brine shrimp Artemia
      sinica prophenoloxidase (AsproPO) cDNA was cloned and its expression at early
      developmental stages was examined by reverse-transcription PCR (RT-PCR) and semi
      quantitative RT-PCR, and activity of phenoloxidase (PO) at different
      developmental stages was further detected by using l-3,4-dihydroxyphenylalanine
      (l-DOPA) as a specific substrate in this study. It was found that the full-length
      of AsproPO cDNA is 2125 bp and it contains an open reading frame of 2100 bp
      encoding a protein of 699 amino acids. The deduced amino acid sequence of AsproPO
      has two putative copper binding sites highly conserved in Arthropods. Semi
      quantitative RT-PCR analyses showed that the gene of AsproPO expressed at
      Emergence, Instar I and Instar II stages but did not at 0 h and 6 h stages.
      Activity measurement showed that PO activity could only be detected at Instar II
      stage but the other measured stages. All these implied that Artemia proPO immune
      system was complexly modulated during early development.

PMID- 21963857
TI  - Over-expression, purification and immune responses to Aeromonas hydrophila AL09
      73 flagellar proteins.
AB  - Aeromonas hydrophila is ubiquitous in aquatic environments worldwide and causes
      many diseases in fish as well as human. Recent outbreaks of aeromonad diseases in
      channel catfish prompted us to investigate catfish immune responses during
      infection of A. hydrophila. In this communication, we report to amplify, over
      express, purify and characterize 19 A. hydrophila flagellar proteins. All
      recombinant proteins were confirmed by nucleotide sequencing of expression
      plasmids, SDS-PAGE analysis and His tag Western blot of induced proteins. Our
      preliminary result also showed that the purified recombinant FlgK protein reacted
      strongly to sera from experimentally infected catfish, suggesting that this
      protein has potential for a novel target for vaccine development. It is also
      anticipated that these recombinant proteins will provide us with very useful
      tools to investigate host immune response to this microorganism.

PMID- 21963858
TI  - Outcomes after Descemet stripping endothelial keratoplasty in glaucoma patients
      with previous trabeculectomy and tube shunt implantation.
AB  - PURPOSE: To describe the incidence of intraoperative and postoperative
      complications and visual outcomes in eyes with previous penetrating glaucoma
      surgery undergoing Descemet stripping endothelial keratoplasty (DSEK). METHODS: A
      retrospective review of the first 227 cases of DSEK performed by 2 surgeons at a
      single institution. Data were collected regarding the performance of concurrent
      ocular procedures, intraoperative complications, postoperative visual outcomes,
      and postoperative complications, including primary graft failure, donor
      dislocation, endothelial rejection, and intraocular pressure (IOP) elevation.
      RESULTS: Fifty-six of the 227 DSEK procedures were performed in 52 eyes with
      previous trabeculectomy and/or tube shunt implantation. The percentage of
      procedures performed in eyes with and without a history of penetrating glaucoma
      surgery that resulted in primary graft failure (5.4% vs. 4.1%; P = 0.71) and
      donor dislocation (12.5% vs. 15.2%; P = 0.83) were not statistically
      significantly different. Additionally, the endothelial rejection rate was not
      significantly different between cases performed in eyes with (1/19.2 eye-years)
      and without (1/20.1 eye-years) a history of glaucoma surgery (P = 0.99). The
      incidence of elevated IOP (>= 25 mm Hg) after DSEK was the highest in eyes with
      medically controlled glaucoma (47.4%), followed by eyes without a history of
      glaucoma (18.3%), and was the lowest in eyes with previous glaucoma surgery
      (11.5%). Postoperative corrected distance visual acuity was improved over the
      preoperative corrected distance visual acuity in 81%, 95%, and 88% of eyes with
      previous glaucoma surgery, medically controlled glaucoma, and no glaucoma,
      respectively. CONCLUSIONS: DSEK is an effective procedure to improve vision in
      the majority of eyes with advanced glaucoma after trabeculectomy and/or tube
      shunt implantation. The incidence of postoperative complications, such as donor
      dislocation, primary graft failure, and endothelial rejection, is not
      significantly higher in eyes with a history of glaucoma surgery before DSEK.
      Because almost 50% of eyes with medically controlled glaucoma before DSEK
      experienced IOP elevation after surgery, careful monitoring of the IOP after DSEK
      is especially important in this patient population.

PMID- 21963859
TI  - Endothelial cell density before and after the preparation of corneal lamellae for
      Descemet membrane endothelial keratoplasty with a stromal rim.
AB  - PURPOSE: To assess the endothelial cell density before and after the preparation
      of precut posterior corneal lamellae for Descemet membrane (DM) endothelial
      keratoplasty with a stromal rim with the aim of standardizing this new technique
      and establishing the parameters of corneas intended for manual preparation under
      the conditions of an ocular tissue bank. METHODS: Two groups of corneoscleral
      buttons were used to prepare lamellae consisting of a central zone of endothelium
      DM surrounded by a supporting peripheral stromal rim. Group 1 contained 12
      corneas with a live endothelial cell density (LECD) of 2500 cells per square
      millimeter or more. Group 2 contained 10 corneas with a density of 2500 cells per
      square millimeter or less. The preparation was performed manually using an
      artificial anterior chamber. The endothelial cell density (ECD) and the
      percentage of dead cells were assessed before and immediately after preparation
      and after 48 hours of organ culture storage at 31 degrees C. RESULTS: Immediately
      after preparation, on average, 4.9% and 5.2% of dead cells were found in group 1
      and group 2, respectively. After 48 hours of storage, the percentage decreased
      significantly in both the groups. There was no significant decrease in the ECD 48
      hours after preparation in group 1; however, there was a significant decrease in
      group 2. The amount of tissue wasted during preparation was 24%. CONCLUSIONS: The
      decrease in ECD is dependent on the initial values: the cell loss is less in
      corneas with higher original densities. We suggest that the minimal acceptable
      LECD of lamellae should be 2500 cells per square millimeter.

PMID- 21963860
TI  - Comparison of corneal surface higher-order aberrations after endothelial
      keratoplasty, femtosecond laser-assisted keratoplasty, and conventional
      penetrating keratoplasty.
AB  - PURPOSE: To evaluate and compare corneal higher-order aberrations (HOAs) after
      Descemet stripping automated endothelial keratoplasty (DSAEK), femtosecond laser
      assisted penetrating keratoplasty (FLAK), and conventional penetrating
      keratoplasty (PKP). METHODS: A retrospective comparison of consecutive surgical
      series of 67 eyes of 59 patients between 1.5 and 19 months after corneal
      transplant surgery (22, 34, and 11 corneas underwent DSAEK, FLAK, and PKP,
      respectively, by a single surgeon). The main outcome measures were anterior and
      posterior corneal surface HOAs (Zernike polynomials, third to eighth order)
      determined with Scheimpflug photography at 4.0- and 6.0-mm optical zones and best
      spectacle-corrected visual acuity (BSCVA) (logarithm of the minimum angle of
      resolution equivalents). RESULTS: DSAEK had fewer total anterior HOAs compared
      with FLAK [P = 5.27 * 10(-5) (4.0 mm) and P = 1.02 * 10(-5) (6.0 mm)] and PKP [P
      = 1.82 * 10(-4) (4.0 mm) and P = 1.56 * 10(-4) (6.0 mm)] but greater total
      posterior HOAs than FLAK [P = 0.001 (4.0 mm) and P = 0.007 (6.0 mm)] and PKP [at
      4.0-mm optical zone (P = 0.047)]. FLAK had fewer total anterior and posterior
      HOAs than PKP, but differences were not statistically significant. DSAEK grafts
      exhibited statistically significantly greater posterior HOAs than either type of
      PKP. The magnitude of anterior and posterior HOAs weakly correlated with BSCVA.
      CONCLUSIONS: DSAEK induces fewer anterior surface HOAs but greater posterior
      surface HOAs than FLAK or PKP. Differences between FLAK and PKP are not
      statistically significant. Anterior and posterior HOAs correlate weakly with
      poorer visual outcome and likely contribute to decreased BSCVA after
      keratoplasty.

PMID- 21963861
TI  - The Boston keratoprosthesis type II: the Massachusetts Eye and Ear Infirmary
      experience.
AB  - PURPOSE: To report the long-term outcomes of Boston keratoprosthesis type II
      implantation in the management of severe ocular surface disease and corneal
      blindness through a retrospective interventional case series. METHODS: This
      retrospective review included medical records of patients who underwent Boston
      keratoprosthesis type II implantation at the Massachusetts Eye and Ear Infirmary
      from January 1, 2000 through December 31, 2009. The main outcome measures
      analyzed were visual acuity, keratoprosthesis retention, and postoperative
      complications. RESULTS: A total of 29 eyes of 26 patients received a Boston
      keratoprosthesis type II during the study period. Patients undergoing operation
      had corneal blindness because of mucous membrane pemphigoid (51.7%), Stevens
      Johnson syndrome/toxic epidermal necrolysis (41.4%), or other ocular surface
      disease (6.9%). Visual acuity after surgery improved to 20/200 or better in 23
      eyes (79.3%) and to 20/30 or better in 10 eyes (34.5%). In patients with at least
      1 year of follow-up (n = 21), visual acuity of 20/200 or better was maintained in
      12 eyes (57.1%). Of 13 eyes followed-up for more than 5 years, 6 eyes (46.2%) had
      visual acuity of 20/200 or better at the last follow-up examination. Eyes that
      did not improve to 20/200 or lost vision during the follow-up had end-stage
      glaucoma, previous retinal detachment, or age-related macular degeneration. Of
      the total of 29 eyes, 17 devices (58.6%) were retained without extrusion or
      replacement during a total follow-up time of 107.9 person-years. CONCLUSIONS: The
      Boston keratoprosthesis type II is a viable option for corneal blindness from
      severe autoimmune ocular surface diseases.

PMID- 21963862
TI  - A zygomycetes-contaminated corneal graft harvested from a donor with signs of
      orbital trauma.
AB  - PURPOSE: To report the clinical features and histopathology of a transplanted
      cornea that was immediately replaced because of the possible diagnosis of lattice
      corneal dystrophy in the graft in which histopathologic examination revealed a
      Zygomycetes infection. METHODS: A 19-year-old patient with keratoconus underwent
      deep anterior lamellar keratoplasty (DALK) in the right eye. The operation was
      uneventful, transplanting a corneal graft without Descemet membrane, harvested
      from a donor with signs of orbital trauma. RESULTS: Three days after
      keratoplasty, multiple refractile lines involving the entire donor stroma were
      observed. With the potential diagnosis of lattice dystrophy of the donor cornea,
      the graft was replaced and sent for histopathologic analysis, which revealed a
      Zygomycetes graft infection. CONCLUSIONS: This case report introduces Zygomycetes
      as a cause of donor-to-host infection and also suggests that corneas harvested
      from donors with signs of orbital trauma may be a risk factor for donor-to
      recipient transmission of such fungal infections.

PMID- 21963863
TI  - Treatment of a large corneal perforation with a multilayer of amniotic membrane
      and TachoSil.
AB  - OBJECTIVE: To describe a novel surgical technique for the sealing of large
      corneal perforations. METHOD: Case report of a perforated, 3-mm, postherpetic,
      corneal ulcer. A single layer of amniotic membrane was sewn to the internal
      surface of the cornea. An absorbable fibrin sealant patch (TachoSil) was placed
      in the area of the perforation, and a folded double layer of amniotic membrane
      was finally sewn to the external face of the cornea. RESULT: Surgery without
      complications, leading to restoration of the anterior chamber and good subjective
      tolerance. CONCLUSION: The reported technique seems to represent a good
      alternative emergency procedure for the management of corneal perforations larger
      than 2 mm.

PMID- 21963864
TI  - Identification, cloning and regulation of cDNA encoding aldo-keto reductase 1B7
      in the adrenal gland of two Saharan rodents Meriones libycus (Libyan jird) and
      Gerbillus gerbillus (gerbil).
AB  - Aldo-Keto Reductase 1B7 (AKR1B7) is a mouse aldose reductase-like protein with
      two major sites of expression, the vas deferens and the adrenal cortex. In the
      adrenal cortex, Akr1b7 is an adrenocorticotropin (ACTH)-responsive-gene whose
      product scavenges harmful byproducts of steroidogenesis and limits stress
      response through the biosynthesis of prostaglandin F2alpha. The purpose of the
      present study was to explore the possible expression of AKR1B7 in the adrenal
      glands of two saharan rodents, Libyan jird and Lesser Egyptian gerbil. Western
      blot analyses demonstrated that a protein related to murine/rat AKR1B7 was highly
      expressed in adrenals and absent from vas deferens of both saharan species. Based
      on conserved sequences between mouse and rat, full length cDNA were cloned and
      sequenced in both species while hormonal regulation and tissue localization were
      explored in Libyan jird. Both cDNA encoded the expected 316 amino acids protein
      typical of AKR1B subfamily and contained the highly conserved catalytic tetrad
      consisting in Asp-44, Tyr-49, Lys-78 and His-111 residues. The deduced proteins
      shared higher identities with aldose reductase-like, i.e. AKR1B7 (86-94%), AKR1B8
      and AKR1B10 (83-86%) than with aldose reductase group, i.e. AKR1B1 and AKR1B3
      (70%). Phylogenetic analysis showed that the Libyan jird and gerbil enzymes were
      more closely related to murine and rat AKR1B7 than to the other AKR1B members.
      Northern blot analyses of total RNA from Libyan jird adrenals showed a single
      mRNA transcript of 1.4 kb whose expression was dependent on circulating ACTH
      levels. In conclusion, we demonstrate here that adrenal glands of Libyan jird and
      gerbil express both an ortholog of the murine/rat Akr1b7 gene and that ACTH
      responsiveness is at least conserved in Libyan jird.

PMID- 21963865
TI  - Searching for a therapy of creatine transporter deficiency: some effects of
      creatine ethyl ester in brain slices in vitro.
AB  - Creatine, an ergogenic compound essential for brain function, is very hydrophilic
      and needs a transporter to cross lipid-rich cells' plasma membranes. Hereditary
      creatine transporter deficiency is a severe incurable neurological disease where
      creatine is missing from the brain. Creatine esters are more lipophylic than
      creatine and may not need the transporter to cross plasma membranes. Thus, they
      may represent a useful therapy for hereditary creatine transporter deficiency.
      Creatine ethyl ester (CEE) is commercially available and widely used as a
      nutritional supplement. It was reported that it enters the cells of patients
      lacking the transporter but was not useful when administered in vivo, by oral
      route, to affected patients. In this paper we investigated the effects of CEE in
      in vitro brain slices before and after biochemical block of the creatine
      transporter. We found that CEE is rapidly degraded in the aqueous incubation
      medium to creatinine, however it remains in solution long enough to cause an
      increase in tissue content of creatine and, more prominently, phosphocreatine.
      Both CEE and creatine delayed the anoxia-induced failure of synaptic
      transmission, and there was no difference between the two compounds. Contrary to
      what we expected, CEE did not increase tissue creatine content after the creatine
      transporter was blocked. We confirm that CEE is probably not an effective
      treatment for hereditary creatine transporter deficiency. Two factors seem to
      affect the possibility for creatine esters to be exploited in the therapy of
      creatine transporter deficiency. First, the size of their alcohol moiety should
      be increased since this would increase the lipophilicity of the compound and
      improve its ability to diffuse through biological membranes. Second, creatine
      esters should be further modified to slow their degradation to creatinine and
      increase their half-life in aqueous solutions. Moreover, we should not forget the
      possibility that they are degraded in vivo by plasma esterases.

PMID- 21963866
TI  - The CC chemokine receptor 5 regulates olfactory and social recognition in mice.
AB  - Chemokines are chemotactic cytokines that regulate cell migration and are thought
      to play an important role in a broad range of inflammatory diseases. The
      availability of chemokine receptor blockers makes them an important therapeutic
      target. In vitro, chemokines are shown to modulate neurotransmission. However, it
      is not very clear if chemokines play a role in behavior and cognition. Here we
      evaluated the role of CC chemokine receptor 5 (CCR5) in various behavioral tasks
      in mice using Wt (Ccr5+/+) and Ccr5-null (Ccr5-/-)mice. Ccr5-/- mice showed
      enhanced social recognition. Administration of CC chemokine ligand 3 (CCL3), one
      of the CCR5-ligands, impaired social recognition. Since the social recognition
      task is dependent on the sense of olfaction, we tested olfactory recognition for
      social and non-social scents in these mice. Ccr5-/- mice had enhanced olfactory
      recognition for both these scents indicating that enhanced performance in social
      recognition task could be due to enhanced olfactory recognition in these mice.
      Spatial memory and aversive memory were comparable in Wt and Ccr5-/- mice.
      Collectively, these results suggest that chemokines/chemokine receptors might
      play an important role in olfactory recognition tasks in mice and to our
      knowledge represents the first direct demonstration of an in vivo role of CCR5 in
      modulating social behavior in mice. These studies are important as CCR5 blockers
      are undergoing clinical trials and can potentially modulate behavior.

PMID- 21963867
TI  - The structure of networks that produce the transformation from grid cells to
      place cells.
AB  - Since grid cells were discovered in the medial entorhinal cortex, several models
      have been proposed for the transformation from periodic grids to the punctate
      place fields of hippocampal place cells. These prior studies have each focused
      primarily on a particular model structure. By contrast, the goal of this study is
      to understand the general nature of the solutions that generate the grids-to
      places transformation, and to exploit this insight to solve problems that were
      previously unsolved. First, we derive a family of feedforward networks that
      generate the grids-to-places transformations. These networks have in common an
      inverse relationship between the synaptic weights and a grid property that we
      call the normalized offset. Second, we analyze the solutions of prior models in
      terms of this novel measure and found to our surprise that almost all prior
      models yield solutions that can be described by this family of networks. The one
      exception is a model that is unrealistically sensitive to noise. Third, with this
      insight into the structure of the solutions, we then construct explicitly
      solutions for the grids-to-places transformation with multiple spatial maps, that
      is, with place fields in arbitrary locations either within the same (multiple
      place fields) or in different (global remapping) enclosures. These multiple maps
      are possible because the weights are learned or assigned in such a way that a
      group of weights contributes to spatial specificity in one context but remains
      spatially unstructured in another context. Fourth, we find parameters such that
      global remapping solutions can be found by synaptic learning in spiking neurons,
      despite previous suggestions that this might not be possible. In conclusion, our
      results demonstrate the power of understanding the structure of the solutions and
      suggest that we may have identified the structure that is common to all robust
      solutions of the grids-to-places transformation.

PMID- 21963868
TI  - Synaptic profile of nucleus tractus solitarius neurons involved with the
      peripheral chemoreflex pathways.
AB  - The glomus cells in the carotid bodies (CB) detect alterations in pH and pCO2 and
      low pO2 level in arterial blood. The carotid sinus nerve conveys the information
      related to the oxygen level to 2nd-order neurons in the nucleus tractus
      solitarius (NTS) via tractus solitarius (TS), which is part of the chemoreflex
      pathways. It has been demonstrated that in 2nd-order NTS neurons receiving inputs
      from the aortic depressor nerve (ADN), the TS stimulation presents high temporal
      fidelity. However, the temporal properties of synaptic activity in NTS neurons
      receiving inputs from CB were not yet fully investigated. Herein using patch
      clamp recordings in NTS brainstem slices, we studied TS-evoked excitatory
      postsynaptic currents (TS-eEPSCs) on morphologically identified 2nd-order NTS
      neurons that receive afferent inputs from the CB and compared with 2nd-order ADN
      NTS neurons recorded in the same experimental conditions. The amplitudes of TS
      eEPSCs were similar in both groups, but the latencies and standard deviation (SD)
      of latency were significantly higher in the CB-NTS neurons (latency: 4+/-0.2 ms,
      SD: 0.49+/-0.03 ms) than in ADN-NTS neurons (latency: 3.3+/-0.3 ms, SD: 0.19+/
      0.02 ms; P=0.049 for latency and P<0.001 for SD of latency). In a series of
      double-labeling experiments, we confirmed that some CB-NTS 2nd-order neurons send
      direct projections to the rostral ventrolateral medulla (RVLM). We conclude that:
      (a) CB-NTS 2nd-order neurons present temporally distinct postsynaptic currents
      when compared with ADN-NTS 2nd-order neurons; (b) low SD of latency of TS-eEPSCs
      is not necessarily a characteristic of all 2nd-order neurons in the NTS; and (c)
      the presence of direct connections between these 2nd-order neurons in the NTS and
      RVLM is indicative that these synaptic properties of CB-NTS neurons are relevant
      for the processing of respiratory and autonomic responses to chemoreflex
      activation.

PMID- 21963869
TI  - Driver report of improper seat belt position among 4- to 9-year-old children.
AB  - OBJECTIVE: To determine the frequency with which drivers report improper seat
      belt positions among children 4-9 years of age and the frequency with which
      reported problems were attributable to the lap belt, shoulder belt, or both.
      SUBJECTS AND METHODS: Analysis of driver responses to 5 questions related to seat
      belt positioning from the cross-sectional, phone-based 2007 Motor Vehicle
      Occupant Safety Survey. Belt position problems categorized as related to (1)
      shoulder belt and (2) lap belt. Improper belt position was compared across age
      groups (4-6 years, 7-8 years, and 9 years) and use of a child safety seat with
      chi(2) statistics or Fisher exact tests as appropriate. RESULTS: Seat belt use
      was reported for 334 of 891 (37%) 4- to 9-year-old child passengers, and 261
      (78%) drivers reported improper belt fit among these child passengers. Improper
      shoulder belt position (44%) was less common than improper lap belt position
      (62%). At least one improper belt position was reported by 78% of drivers of 4-
      to 6-year-old children, 77% of 7- to 8-year-old children, and 79% of 9-year-old
      children (P = .87). There were no significant differences in report of improper
      belt position among children who never and those who occasionally use a child
      safety seat were compared. CONCLUSIONS: Drivers frequently report improper lap
      and shoulder belt positions for their 4- to 9-year-old child passengers yet
      persist in restraining children by the use of seat belts alone. Clinicians can
      promote the use of size-appropriate child passenger restraint systems, including
      car seats and booster seats, to overcome the improper belt positions identified
      in this study.

PMID- 21963870
TI  - Blood stage merozoite surface protein conjugated to nanoparticles induce potent
      parasite inhibitory antibodies.
AB  - In this proof-of-concept study we report the use of <15 nm, water soluble,
      inorganic nanoparticles as a vaccine delivery system for a blood stage malaria
      vaccine. The recombinant malarial antigen, Merozoite Surface Protein 1 (rMSP1) of
      Plasmodium falciparum served as the model vaccine. The rMSP1 was covalently
      conjugated to polymer-coated quantum dot CdSe/ZnS nanoparticles (QDs) via surface
      carboxyl groups, forming rMSP1-QDs. Anti-MSP1 antibody responses induced by rMSP1
      QDs were found to have 2-3 log higher titers than those obtained with rMSP1
      administered with the conventional adjuvants, Montanide ISA51 and CFA. Moreover,
      the immune responsiveness and the induction of parasite inhibitory antibodies
      were significantly superior in mice injected with rMSP1-QDs. The rMSP1-QDs
      delivered via intra-peritoneal (i.p.), intra-muscular (i.m.), and subcutaneous
      (s.c.) routes were equally efficacious. The high level of immunogenicity
      exhibited by the rMSP1-QDs was achieved without further addition of other
      adjuvant components. Bone marrow derived dendritic cells were shown to
      efficiently take up the nanoparticles leading to their activation and the
      expression/secretion of key cytokines, suggesting that this may be a mode of
      action for the enhanced immunogenicity. This study provides promising results for
      the use of water soluble, inorganic nanoparticles (<15 nm) as potent
      vehicles/platforms to enhance the immunogenicity of polypeptide antigens in
      adjuvant-free immunizations.

PMID- 21963871
TI  - Vaccination with drifted variants of avian H5 hemagglutinin protein elicits a
      broadened antibody response that is protective against challenge with homologous
      or drifted live H5 influenza virus.
AB  - Substantial H5 influenza HA directed immunity is elicited after vaccination of
      human subjects who had been previously immunized with a drifted H5 HA variant. We
      sought to investigate the characteristics of H5 HA specific immune responses in
      more depth by developing an animal model of H5 HA vaccination using drift
      variants of recombinant H5 HA proteins. HA proteins derived from influenzas
      A/Vietnam/1203/04 (Clade 1) and A/Indonesia/05/05 (Clade 2.1) were chosen. The
      sequence of vaccination consisted of two doses of homologous protein, followed by
      one additional dose of the homologous or heterologous, drifted HA protein. Each
      dose of HA was combined with CpG as an adjuvant and was injected subcutaneously.
      All the animals exhibited a serum IgG antibody response that cross-reacted with
      both HAs in an ELISA. However, those animals that received the drifted variant
      exhibited higher reactivity to the heterologous HA. Competitive ELISA of serum
      from drift-variant recipients showed evidence of antibody focusing towards the
      drifted HA, suggesting modification of the response towards improved cross
      reactivity, though development of neutralizing antibodies was limited.
      Nevertheless, animals were protected against live-virus challenge, and passive
      transfer of serum was sufficient to confer protection to otherwise naive mice,
      indicating that both neutralizing and non-neutralizing antibodies offer some
      degree of protection. These findings suggest that pre-vaccination against H5
      influenza has the potential to prime immunity against emerging drifted H5
      strains, and could also lower the dose requirements of vaccination in the event
      of a pandemic.

PMID- 21963872
TI  - Adjuvants that stimulate TLR3 or NLPR3 pathways enhance the efficiency of
      influenza virus-like particle vaccines in aged mice.
AB  - There is intense interest in the design and use of vaccine strategies against
      influenza to enhance protective immune responses in the elderly. To address the
      need for improved influenza vaccines for the aged, two inflammatory adjuvants,
      Imject((r)) alum (a stimulator of the Nod-like receptor, Nalp3) and poly I:C (a
      toll-like receptor type 3 ligand), were used during vaccination with novel
      influenza virus-like particles (VLP). Adult (4 month old) or aged (24 month old)
      mice were vaccinated with VLPs alone or in combination with adjuvant. VLP
      vaccinated adult mice were protected from a lethal influenza virus challenge
      without the use of either adjuvant. In contrast, only aged mice that were
      vaccinated with VLPs plus adjuvant survived challenge, whereas ~33% of the mice
      vaccinated with VLP only survived challenge. Mice vaccinated with adjuvant only
      did not survive challenge despite similar levels of activation of
      CD11b(+)/CD11c(+) dendritic cells in the lungs. The protection was not associated
      with HAI titers or HA specific CD8(+) T cells, since both adjuvants boosted the
      VLP-induced serum HAI titers and CD8(+) responses in adult mice, but not aged
      mice. Influenza VLPs used in combination with two different inflammatory
      adjuvants during vaccination allow for the immune system to overcome the
      deficiency in the aged immune system to influenza virus infection.

PMID- 21963873
TI  - Dynamics of Streptococcus pneumoniae nasopharyngeal carriage with high
      heptavalent pneumococcal conjugate vaccine coverage in Central Greece.
AB  - In order to study whether the use of the heptavalent pneumococcal conjugate
      vaccine (PCV7) led to a shift in the Streptococcus pneumoniae serotypes
      distribution and whether it modified the resistance to antibiotics, 2649
      nasopharyngeal samples were obtained between 2005 and 2009, from children
      attending day-care centers in Central Greece. The percentage of attendees
      vaccinated with >=1 dose of PCV7 increased from 12.9% (2005) to 95.5% (2009). Non
      PCV7 serotypes replaced those belonging to PCV7. In 2009, 19F was virtually the
      only PCV7 serotype that continued to circulate. A significant increase in the
      frequency of penicillin-intermediate (oral penicillin V breakpoints) isolates
      coincided with a marked reduction in isolates with high resistance to penicillin.
      Several non-PCV7 serotypes colonized the children, but their frequency varied
      substantially from year to year. Each one of 14 specific non-PCV7 serotypes, i.e.
      6A, 11A, 15B, 23A, 10A, 16F, 38, 22F, 15C, 19A, 35F, 24F, 6C, and 7F, accounted
      for >=2% of pneumococcal isolates in at least 2 annual surveillances. An increase
      in non-PCV7 serotypes with antibiotic resistance, beyond 6A and 19A, occurred.
      Intermediate resistance to penicillin was observed in serotype 23B, 15B, 15C,
      15A, 35F, 6C, and 24F pneumococci. Their exact role in invasive and non-invasive
      disease remains to be seen in the years ahead.

PMID- 21963874
TI  - Influence of solvents on the morphological properties of AgBr nano-structures
      prepared using ultrasound irradiation.
AB  - Nano-structures of AgBr have been prepared by reaction between AgNO(3) and KBr
      under ultrasound irradiation. Particle sizes and morphology of nanoparticle are
      depending on temperature, power of sonicating, reaction time and concentration.
      The effects of these parameters in growth and morphology of the nano-structures
      have been studied. Results suggest that an increasing of temperature, sonication
      power and concentration led to a decreasing of particle size. The samples were
      characterized with powder X-ray diffraction (XRD) and scanning electron
      microscopy (SEM).

PMID- 21963875
TI  - Stress and skin leukocyte trafficking as a dual-stage process.
AB  - Stress responses are known to modulate leukocyte trafficking. In the skin, stress
      was reported both to enhance and reduce skin immunity, and the chronicity of
      stress exposure was suggested as a key determining factor. We here propose a dual
      stage hypothesis, suggesting that stress, of any duration, reduces skin immunity
      during its course, while its cessation is potentially followed by a period of
      enhanced skin immunity. To start testing this hypothesis, rats were
      subcutaneously implanted with sterile surgical sponges for four-hours, during or
      after exposure to one of several acute stress paradigms, or to a chronic stress
      paradigm. Our findings, in both males and females, indicate that numbers of
      sponge-infiltrating leukocytes, and their specific subsets, were reduced during
      acute or chronic stress, and increased after stress cessation. Studying potential
      mediating mechanisms of the reduction in leukocyte numbers during acute stress,
      we found that neither adrenalectomy nor the administration of beta-adrenergic or
      glucocorticoid antagonists prevented this reduction. Additionally, administration
      of corticosterone or epinephrine to adrenalectomized rats did not impact skin
      leukocyte numbers, whereas, in the blood, these treatments did affect numbers of
      leukocytes and their specific subsets, as was also reported previously. Overall,
      our findings support the proposed dual-stage hypothesis, which can be
      evolutionally rationalized and accounts for most of the apparent inconsistencies
      in the literature regarding stress and skin immunity. Other aspects of the
      hypothesis should be tested, also using additional methodologies, and its
      predictions may bear clinical significance in treatment of skin disorders related
      to hyper- or hypo-immune function.

PMID- 21963876
TI  - The evolving role of stem cell transplants in lymphomas.
AB  - Autologous stem cell transplantation (ASCT) is an established therapeutic
      modality in the treatment of lymphomas, especially in the relapse setting. It is
      also under investigation after first-line therapy, for example, in patients with
      mantle cell or T cell lymphomas. Each year more than 6000 autotransplants for
      lymphomas are reported to the European Blood and Marrow Transplantation (EBMT)
      registry. The number of allogeneic stem cell transplantations (alloSCT) in
      lymphoma patients has increased over the last decade, with about 1200
      transplanted lymphoma patients annually reported to the registry. Optimal timing
      and indications for alloSCT are not well defined because of absence of randomized
      trials. Developments in the treatment of lymphomas including immunotherapy have
      changed the clinical scenarios in regard to ASCT, and many published studies are
      now outdated. On the other hand, patients relapsing after immunochemotherapy may
      derive less benefit from ASCT. Consequently, there is an increasing interest in
      using alloSCT not only in lymphoma patients relapsing after ASCT but also in
      earlier phases in specific circumstances. Although curative potential is higher
      with alloSCT compared with ASCT, its wider use has been hindered by excessive
      nonrelapse mortality (NRM). Along with decreasing NRM figures, popularity of
      alloSCT may increase in the near future, possibly with the expense of ASCT.
      Prospective, randomized studies are needed to evaluate feasibility and efficacy
      of alloSCT in several clinical settings, as most published evidence is based on
      retrospective registry data or single-center experiences.

PMID- 21963878
TI  - Impact of HLA-DPB1 haplotypes on outcome of 10/10 matched unrelated hematopoietic
      stem cell donor transplants depends on MHC-linked microsatellite polymorphisms.
AB  - Hematopoietic stem cell transplantation (HSCT) with HLA-A, -B, -C, -DRB1, -DQB1
      allele matched (10 of 10) unrelated donors is still associated with a significant
      rate of posttransplantation complications. In order to disclose additional
      immunogenetic factors, we analyzed the impact of HLA-DPB1 disparities and major
      histocompatibility complex (MHC)-resident microsatellite polymorphisms in 246 HLA
      10 of 10 matched HSCT patients. First we showed that patients with more
      frequent/conserved HLA haplotypes had a higher 5-year survival (55% +/- 18%
      versus 39% +/- 18%, P = .021). In addition, DPB1 incompatibilities and 3
      microsatellite alleles were associated with outcome. In a Cox regression model
      adjusting for European Blood and Marrow Transplant (EBMT) risk score, T cell
      depletion, and year of treatment, HSCT with a tumor necrosis factor d (TNFd) 4/d5
      positive donor was associated with increased mortality (hazard ratio [HR] = 2.03;
      confidence interval [CI] 1.25-3.31; P = .004), whereas the D6S510-184 allele was
      protective (HR = 0.44; CI 0.22-0.87; P = .018). The 2 MHC-linked genetic donor
      factors, DPB1 mismatch (MM), and TNFd4/d5-positivity, acted in synergy with the
      EBMT risk score with an always lower survival (HR = 2.97; CI 1.27-6.92; P =
      .012). These data show that multiple MHC-linked genetic donor factors impact on
      outcome after unrelated donor HSCT. Their additive and potentially divergent
      effects could explain previous discrepant results, particularly with respect to
      the role of HLA-DPB1 disparities. We conclude that HLA-DPB1 typing combined with
      a simple TNFd microsatellite genotyping assay may significantly help in
      pretransplantation risk assessment for graft-versus-host disease and mortality,
      particularly for patients with several potential 10 of 10 matched donors.

PMID- 21963879
TI  - A clinical study of cervical dysplasia in long-term survivors of allogeneic stem
      cell transplantation.
AB  - This retrospective study examined the prevalence of and risk factors for cervical
      dysplasia and genital human papillomavirus (HPV) infection in 89 female
      recipients of allogeneic stem cell transplantation (allo-SCT) between 1985 and
      2005 who survived for more than 5 years after transplantation. All patients
      underwent regular gynecologic examination and cervical cytological testing. The
      incidence rates of cervical cytological abnormalities and HPV infection were
      calculated. Various clinical parameters were evaluated for association with
      cytological high-grade squamous intraepithelial lesion (HSIL) posttransplantation
      to identify risk factors for cervical dysplasia. Multivariate analysis with
      logistic regression was used to identify independent risk factors for cervical
      dysplasia after adjusting for confounding factors. Sixty-one of the 89 patients
      (68.5%) had cervical cytological abnormalities of varying grades, including
      atypical squamous cells of undetermined significance (ASC-US; 31.5%; 28 of 89),
      low-grade squamous intraepithelial lesion (LSIL; 10.1%; 9 of 89), and HSIL (27%;
      24 of 89). HPV status was available for 43 patients, 12 of whom (27.9%) were HPV
      positive. Among the 69 patients with normal cytological cervical smear findings
      pretransplantation, the incidence of cytological HSIL was 23.2% (16 of 69)
      posttransplantation. After adjusting for confounding factors, only unrelated HLA
      matched donor and the presence of vulvovaginal chronic graft-versus-host disease
      (cGVHD) were independent risk factors for cervical cytology HSIL after
      transplantation, with the highest risk among patients with vulvovaginal cGVHD
      (adjusted odds ratio, 31.97). We conclude that long-term survivors of allogeneic
      stem cell transplantation are at high risk for cervical cytological
      abnormalities. Vulvovaginal cGVHD and unrelated HLA-matched donor were the only
      independent risk factors for cervical cytological HSIL in patients with normal
      cervical cytology before transplantation. Regular surveillance by gynecologic
      examination, including cervical cytological testing, in these patients allows for
      early diagnosis and effective management of cervical abnormality and decreases
      the burden of this potentially fatal, but treatable, condition.

PMID- 21963880
TI  - Keratinocyte growth factor and stem cell factor to improve thymopoiesis after
      autologous CD34+ cell transplantation in rhesus macaques.
AB  - Deficient thymopoiesis and retarded recovery of naive CD4(+) T cells are
      important determinants of insufficient immune-competence following hematopoietic
      stem cell transplantation (HSCT). Although keratinocyte growth factor (KGF) may
      protect the thymic epithelium, stem cell factor (SCF) is involved in early
      thymopoiesis. We evaluated whether KGF alone or combined with SCF would affect
      thymopoiesis and hematologic recovery following myeloablative autologous HSCT
      into rhesus macaques. Purpose-bred adult rhesus macaques received 10(6)
      autologous CD34(+)-selected mononuclear bone marrow cells (BMC)/kg after 9 Gy
      myeloablative conditioning. Animals were treated with phosphate-buffered saline
      (PBS) (n = 2), KGF alone (n = 2), or KGF combined with SCF (n = 2). KGF-treated
      animals showed accelerated hematologic recovery, improved thymopoiesis, and
      enhanced naive T-cell recovery following transplantation. Improved T cell
      recovery was not associated with protection against cytomegalovirus reactivation
      nor with improved antibody response to tetanus toxoid vaccination. Animals
      treated with KGF and SCF experienced severe adverse events that precluded
      evaluation of thymopoiesis and T cell recovery. Collectively, our data confirm
      that KGF may enhance thymopoiesis.

PMID- 21963877
TI  - National Cancer Institute-National Heart, Lung and Blood Institute/pediatric
      Blood and Marrow Transplant Consortium First International Consensus Conference
      on late effects after pediatric hematopoietic cell transplantation: long-term
      organ damage and dysfunction.
AB  - Long-term complications after hematopoietic cell transplantation (HCT) have been
      studied in detail. Although virtually every organ system can be adversely
      affected after HCT, the underlying pathophysiology of these late effects remain
      incompletely understood. This article describes our current understanding of the
      pathophysiology of late effects involving the gastrointestinal, renal, cardiac,
      and pulmonary systems, and discusses post-HCT metabolic syndrome studies.
      Underlying diseases, pretransplantation exposures, transplantation conditioning
      regimens, graft-versus-host disease, and other treatments contribute to these
      problems. Because organ systems are interdependent, long-term complications with
      similar pathophysiologic mechanisms often involve multiple organ systems. Current
      data suggest that post-HCT organ complications result from cellular damage that
      leads to a cascade of complex events. The interplay between inflammatory
      processes and dysregulated cellular repair likely contributes to end-organ
      fibrosis and dysfunction. Although many long-term problems cannot be prevented,
      appropriate monitoring can enable detection and organ-preserving medical
      management at earlier stages. Current management strategies are aimed at
      minimizing symptoms and optimizing function. There remain significant gaps in our
      knowledge of the pathophysiology of therapy-related organ toxicities disease
      after HCT. These gaps can be addressed by closely examining disease biology and
      identifying those patients at greatest risk for adverse outcomes. In addition,
      strategies are needed for targeted disease prevention and health promotion
      efforts for individuals deemed at high risk because of their genetic makeup or
      specific exposure profile.

PMID- 21963881
TI  - Genetic characterization of the endangered Kiso horse using 31 microsatellite
      DNAs.
AB  - In order to contribute to conservation of the endangered Kiso horse, we clarified
      their genetic information using 31 microsatellite DNAs, and genotyped 125 horses,
      83% of the existing breed. First, we clarified the current status of the horses.
      The horses were confirmed to have experienced rapid loss of population causing a
      bottleneck, and their effective population size was much smaller than their
      census size. Moreover, the number of alleles (6.3), observed heterozygosity
      (0.674), and expected heterozygosity (0.662) were in the same range as other
      endangered horses all over the world. Therefore, although their inbreeding level
      was not so severe (F(is): -0.017), the Kiso horse is surely one of the
      endangered. Second, we obtained genetic information of individuals. This
      information allowed us to understand the genetic distance of individuals, and
      might help in development of a reproductive strategy concerning the genetic
      distance between the mating pairs. Moreover, there appeared to be 4
      subpopulations of Kiso horse, and this result was in good agreement with their
      historical background. Third, we confirmed that the parentage test for
      identification using the 31 microsatellite DNAs was highly reliable (probability
      of exclusion: 0.999999993). This identification increases the reliability of stud
      certification, and is also helpful for effective management. Understanding the
      genetic diversity within the population and the relationships among individuals
      is important to ensuring effective management for maintenance of genetic
      variation, and this study may help in conservation of the endangered Kiso horse.

PMID- 21963882
TI  - The AAA-type ATPases Pex1p and Pex6p and their role in peroxisomal matrix protein
      import in Saccharomyces cerevisiae.
AB  - The recognition of the conserved ATP-binding domains of Pex1p, p97 and NSF led to
      the discovery of the family of AAA-type ATPases. The biogenesis of peroxisomes
      critically depends on the function of two AAA-type ATPases, namely Pex1p and
      Pex6p, which provide the energy for import of peroxisomal matrix proteins.
      Peroxisomal matrix proteins are synthesized on free ribosomes in the cytosol and
      guided to the peroxisomal membrane by specific soluble receptors. At the
      membrane, the cargo-loaded receptors bind to a docking complex and the receptor
      docking complex assembly is thought to form a dynamic pore which enables the
      transition of the cargo into the organellar lumen. The import cycle is completed
      by ubiquitination- and ATP-dependent dislocation of the receptor from the
      membrane to the cytosol, which is performed by the AAA-peroxins. Receptor
      ubiquitination and dislocation are the only energy-dependent steps in peroxisomal
      protein import. The export-driven import model suggests that the AAA-peroxins
      might function as motor proteins in peroxisomal import by coupling ATP-dependent
      removal of the peroxisomal import receptor and cargo translocation into the
      organelle.

PMID- 21963883
TI  - Regulation of p97 in the ubiquitin-proteasome system by the UBX protein-family.
AB  - The AAA protein p97 is a central component in the ubiquitin-proteasome system, in
      which it is thought to act as a molecular chaperone, guiding protein substrates
      to the 26S proteasome for degradation. This function is dependent on association
      with cofactors that are specific to the different biological pathways p97
      participates in. The UBX-protein family (ubiquitin regulatory X) constitutes the
      largest known group of p97 cofactors. We propose that the regulation of p97 by
      UBX-proteins utilizes conserved structural features of this family. Firstly, they
      act as scaffolding subunits in p97-containing multiprotein complexes, by
      providing additional interaction motifs. Secondly, they provide regulation of
      multiprotein complex assembly and we suggest two possible models for p97
      substrate recruitment in the UPS pathway. Lastly, they impose constraints on p97
      and its interaction with substrates and further cofactors. These features allow
      the regulation, within the UPS, of the competitive interactions on p97, a
      regulation that is crucial to allow the diverse functionality of p97.

PMID- 21963884
TI  - Altered matrix metalloproteinases and tissue inhibitors of metalloproteinases in
      embryos from diabetic rats during early organogenesis.
AB  - Maternal diabetes increases the risks for embryo malformations. Matrix
      metalloproteinase-2 (MMP-2) and MMP-9 are two relevant MMPs for embryo
      development. Here, we addressed whether changes in these MMPs and in tissue
      inhibitor of matrix metalloproteinase-1 (TIMP-1) and TIMP-2 are altered in
      embryos and decidua from type 1 diabetic rats during early organogenesis. Our
      results demonstrate MMP-2 and MMP-9 overactivities and overexpression, together
      with increases in lipid peroxidation and nitric oxide production in embryos and
      decidua from diabetic animals. There is a concomitant increase in the inhibitory
      activity of TIMP-1 and TIMP-2 in embryos and decidua, and an increase in protein
      expression of embryonic TIMP-1 and TIMP-2. In situ zymography demonstrated MMPs
      overactivities despite increased TIMPs in embryos and decidua in maternal
      diabetes during early organogenesis. This study reveals that maternal diabetes
      leads to profound alterations in MMPs/TIMPs balance during embryo organogenesis,
      the gestational period during which most malformations are induced.

PMID- 21963886
TI  - Selective serotonin reuptake inhibitors (SSRIs) and heart defects: potential
      mechanisms for the observed associations.
AB  - Several epidemiological investigations have shown an association between
      congenital heart defects and the selective serotonin reuptake inhibitor (SSRI)
      class of antidepressants. At first glance this association may not seem to make
      biological sense, especially since, in many cases, serotonin is thought of as a
      neurotransmitter involved in signaling between neurons. However, serotonin also
      acts as a signaling molecule during embryogenesis affecting cell proliferation,
      migration, death, and differentiation. Serotonin may be particularly important
      for heart development and evidence suggests that from the time that progenitor
      heart cells are patterned during the establishment of laterality, to formation of
      the outflow tract, to myocardial cell differentiation, to septation of the heart
      chambers, the neurotransmitter may act as an important signaling molecule. Thus,
      numerous investigations have identified potential target sites where serotonin
      could regulate key cellular processes in cardiac development, thereby providing
      biological plausibility for the origin of heart defects caused by SSRIs.

PMID- 21963885
TI  - Neonatal diethylstilbestrol exposure disrupts female reproductive tract
      structure/function via both direct and indirect mechanisms in the hamster.
AB  - We assessed neonatal diethylstilbestrol (DES)-induced disruption at various
      endocrine levels in the hamster. In particular, we used organ transplantation
      into the hamster cheek pouch to determine whether abnormalities observed in the
      post-pubertal ovary are due to: (a) a direct (early) mechanism or (b) an indirect
      (late) mechanism that involves altered development and function of the
      hypothalamus and/or pituitary. Of the various disruption endpoints and attributes
      assessed: (1) some were consistent with the direct mechanism (altered uterine and
      cervical dimensions/organization, ovarian polyovular follicles, vaginal
      hypospadius, endometrial hyperplasia/dysplasia); (2) some were consistent with
      the indirect mechanism (ovarian/oviductal salpingitis, cystic ovarian follicles);
      (3) some were consistent with a combination of the direct and indirect mechanisms
      (altered endocrine status); and (4) the mechanism(s) for one (lack of corpora
      lutea) was uncertain. This study also generated some surprising observations
      regarding vaginal estrous assessments as a means to monitor periodicity of
      ovarian function in the hamster.

PMID- 21963887
TI  - Investigating the effects of functionalized carbon nanotubes on reproduction and
      development in Drosophila melanogaster and CD-1 mice.
AB  - Despite numerous applications for functionalized carbon nanotubes (fCNTs) in
      consumer products, such as electronics, and food packaging, as well as their
      development as drug delivery vehicles, the consequence of their uptake by living
      systems has been understudied. In particular, the impact of fCNTs on early
      development of different species is largely unknown. Here we investigated the
      effect of ingested hydroxyl-fCNTs on reproduction and development in two model
      organisms: Drosophila and CD-1 mice. While fCNTs had no measurable impact on
      Drosophila, a single oral dose of fCNTs (10mg/kg) administered to pregnant CD-1
      dams during organogenesis significantly increased the number of resorptions and
      resulted in fetal morphological and skeletal abnormalities. The observed
      difference between the responses of these two models likely reflects their
      physiology and/or differences in administration. This research underscores the
      need to examine the effects of fCNTs on reproductive health and development
      before the opportunities for maternal exposure by fCNTs increase further.

PMID- 21963888
TI  - Treating trauma in psychosis with EMDR: a pilot study.
AB  - BACKGROUND: Initial studies have shown that posttraumatic stress disorder (PTSD)
      can be effectivelytreated in patients with a psychotic disorder. These studies
      however used adapted treatment protocols, avoided direct exposure to trauma
      related stimuli or preceded treatment with stabilizing techniques making
      treatment considerably longer in duration. METHOD: An open trial in which adult
      subjects with a psychotic disorder and a comorbid PTSD (n = 27) received a
      maximum of six Eye Movement Desensitization and Reprocessing (EMDR) therapy
      sessions. PTSD symptoms, psychotic symptoms and additional symptoms were assessed
      at baseline and end-of-treatment. RESULTS: The dropout rate was 18.5 percent
      (five subjects). Only five of the twenty-two completers (22.7%) still met
      criteria for PTSD after treatment. PTSD symptoms, auditory verbal hallucinations,
      delusions, anxiety, depression, and self-esteem all improved significantly.
      Paranoid ideation and feelings of hopelessness did not improve significantly.
      Treatment did not lead to symptom exacerbation in subjects. There were no adverse
      events, such as suicide attempts, self-mutilation, aggressive behavior or
      admission to a general or psychiatric hospital. CONCLUSIONS: This pilot study
      shows that a short EMDR therapy is effective and safe in the treatment of PTSD in
      subjects with a psychotic disorder. Treatment of PTSD has a positive effect on
      auditory verbal hallucinations, delusions, anxiety symptoms, depression symptoms,
      and self-esteem. EMDR can be applied to this group of patients without adapting
      the treatment protocol or delaying treatment by preceding it with stabilizing
      interventions.

PMID- 21963889
TI  - Intrusive imagery in people with a specific phobia of vomiting.
AB  - BACKGROUND: AND OBJECTIVES: Specific phobia of vomiting (SPOV) is a chronic,
      pervasive and debilitating disorder which is clinically regarded as difficult to
      treat. Research into its development, maintenance and treatment has been limited.
      This study explored the prevalence and characteristics of intrusive mental
      imagery in people with SPOV. It investigated the relationship between presence of
      imagery and severity of phobia. METHOD: Thirty-six participants meeting DSM-IV
      criteria for SPOV were recruited from online support groups and outpatient
      clinics. A semi-structured quantitative interview was administered. RESULTS:
      Twenty-nine (81%) participants reported multi-sensory intrusive imagery of adult
      (52%) and childhood memories (31%) and worst case scenarios ("flashforwards") of
      vomiting (17%). Extent of imagery was significantly related to severity of
      phobia. Participants primarily fearing others vomiting had less severe phobic
      symptoms. LIMITATIONS: No control group was used and a heterogeneous sample of
      clinical and community participants was recruited. Correlational data comparing
      extent of imagery with severity of SPOV symptoms were derived from as yet
      unvalidated measures. CONCLUSIONS: Intrusive mental imagery is a clinically
      important feature of SPOV and may contribute to its maintenance. Causality needs
      to be demonstrated.

PMID- 21963890
TI  - The relationship between sensory processing, childhood rituals and obsessive
      compulsive symptoms.
AB  - BACKGROUND AND OBJECTIVES: Studies of Obsessive-Compulsive Disorder (OCD) and
      research in occupational therapy suggest a link between sensory hypersensitivity
      and excessive use of rituals. The present research constitutes an initial attempt
      to examine this potential link. METHODS: In Study 1, parents of 4-6-year old
      children (N = 61) completed the Childhood Routine Inventory, the Sensory Profile
      and the Screen for Child Anxiety Related Emotional Disorders. In Study 2 we
      administered an adapted version of the sensory profile to an internet sample of
      adult participants (N = 314) together with the Obsessive-Compulsive Inventory
      Revised, the anxiety subscale of the International Personality Item Pool - NEO
      and items measuring participants' recollection of their childhood oral and
      tactile hypersensitivity. RESULTS: Strong reactions to everyday sensory events
      were highly correlated with childhood ritualism, even after controlling for
      anxiety. In the adult sample, current and recollected oral and tactile
      hypersensitivity were significantly related to OCD symptoms. LIMITATIONS: In
      Study 1, children's sensory sensitivity was not tested directly, but rather
      through parental report. The scale was developed ad hoc based on face validity
      and relationship with ritualism. The studies were cross-sectional in design.
      Study 2 partially relied on recollection of childhood behavior. CONCLUSIONS: The
      results suggest a strong relationship between sensory sensitivity, childhood
      ritualism and adult OCD symptoms. Oral and tactile hypersensitivity in childhood
      may be one pathway to adult OCD.

PMID- 21963891
TI  - Classification of 5-HT(1A) receptor agonists and antagonists using GA-SVM method.
AB  - AIM: To construct a reliable computational model for the classification of
      agonists and antagonists of 5-HT(1A) receptor. METHODS: Support vector machine
      (SVM), a well-known machine learning method, was employed to build a prediction
      model, and genetic algorithm (GA) was used to select the most relevant
      descriptors and to optimize two important parameters, C and r of the SVM model.
      The overall dataset used in this study comprised 284 ligands of the 5-HT(1A)
      receptor with diverse structures reported in the literatures. RESULTS: A SVM
      model was successfully developed that could be used to predict the probability of
      a ligand being an agonist or antagonist of the 5-HT(1A) receptor. The predictive
      accuracy for training and test sets was 0.942 and 0.865, respectively. For
      compounds with probability estimate higher than 0.7, the predictive accuracy of
      the model for training and test sets was 0.954 and 0.927, respectively. To
      further validate our model, the receiver operating characteristic (ROC) curve was
      plotted, and the Area-Under-the-ROC- Curve (AUC) value was calculated to be 0.883
      for training set and 0.906 for test set. CONCLUSION: A reliable SVM model was
      successfully developed that could effectively distinguish agonists and
      antagonists among the ligands of the 5-HT(1A) receptor. To our knowledge, this is
      the first effort for the classification of 5-HT(1A) receptor agonists and
      antagonists based on a diverse dataset. This method may be used to classify the
      ligands of other members of the GPCR family.

PMID- 21963892
TI  - Protective effect of Bu-7, a flavonoid extracted from Clausena lansium, against
      rotenone injury in PC12 cells.
AB  - AIM: To investigate the protective effect and underlying mechanisms of Bu-7, a
      flavonoid isolated from the leaves of Clausena lansium, against rotenone-induced
      injury in PC12 cells. METHODS: The cell viability was evaluated using MTT assay.
      The cell apoptosis rate was analyzed using flow cytometry. JC-1 staining was used
      to detect the mitochondrial membrane potential (MMP). Western blotting analysis
      was used to determine the phosphorylation of c-Jun N-terminal kinase (JNK), p38
      mitogen-activated protein kinase (p38), tumor protein 53 (p53), Bcl-2-associated
      X protein (Bax), B-cell lymphoma 2 (Bcl-2), and caspase 3. RESULTS: Treatment of
      PC12 cells with rotenone (1-20 MUmol/L) significantly reduced the cell viability
      in a concentration-dependent manner. Pretreatment with Bu-7 (0.1 and 10 MUmol/L)
      prevented PC12 cells from rotenone injury, whereas Bu-7 (1 MUmol/L) had no
      significant effect. Pretreatment with Bu-7 (0.1 and 10 MUmol/L) decreased
      rotenone-induced apoptosis, attenuated rotenone-induced mitochondrial potential
      reduction and suppressed rotenone-induced protein phosphorylation and expression,
      whereas Bu-7 (1 MUmol/L) did not cause similar effects. Bu-7 showed inverted bell
      shaped dose-response relationship in all the effects. CONCLUSION: Bu-7 protects
      PC12 cells against rotenone injury, which may be attributed to MAP kinase cascade
      (JNK and p38) signaling pathway. Thus, Bu-7 may be a potential bioactive compound
      for the treatment of Parkinson's disease.

PMID- 21963893
TI  - Polymorphisms of genes in nitric oxide-forming pathway associated with ischemic
      stroke in Chinese Han population.
AB  - AIM: To investigate the association of polymorphisms in four critical genes
      implicated in the NO-forming pathway with ischemic stroke (IS) in a Chinese Han
      population. METHODS: DNA samples of 558 IS patients and 557 healthy controls from
      Chinese Han population were genotyped using the Taqman(TM) 7900HT Sequence
      Detection System. Six SNPs (rs841, rs1049255, rs2297518, rs1799983, rs2020744,
      rs4673) of the 4 related genes (eNOS, iNOS, GCH1, and CYBA) in the NO forming
      pathway were analyzed using the SPSS 13.0 software package for Windows. RESULTS:
      One SNP located in the intron of GCH1 (rs841) was associated with IS independent
      of the traditional cardiovascular risk factors in co-dominant and dominant models
      (P=0.003, q=0.027; P=0.00006, q=0.0108; respectively). Moreover, the combination
      of rs1049255 CC+CT and rs841 GA+AA genotypes was associated with significantly
      higher risk for IS after adjustments (OR=1.73, 95% CI: 1.27-2.35, P<0.0001,
      q<0.0001). CONCLUSION: The data suggest that genetic variants within the NO
      forming pathway alter susceptibility to IS in Chinese Han population. Replication
      of the present results in other independent cohorts is warranted.

PMID- 21963894
TI  - Negative association between free triiodothyronine level and international
      normalized ratio in euthyroid subjects with acute myocardial infarction.
AB  - AIM: To investigate the relationship between free triiodothyronine (FT3) and the
      international normalized ratio (the ratio of the prothrombin time of a patient to
      the normal sample, INR) in Chinese euthyroid subjects with acute ST-segment
      elevation myocardial infarction (STEMI). METHODS: A total of 231 consecutive
      patients (177 males, 54 females) with STEMI were enrolled. Anthropometric and
      laboratory measurements, including heart rate, respiratory rate, blood pressure,
      body temperature, platelet count, INR, prothrombin time, activated partial
      thromboplastin time, FT3, free thyroxine (FT4), and thyroid-stimulating hormone,
      were collected from all the patients. The levels of FT3 and FT4 were measured
      with a full-automatic immune analyzer. The INR was determined using a coagulation
      analyzer. RESULTS: Patients were classified into 4 groups according to their
      quartile FT3 and FT4 levels: 0.40-3.09 (n=52), 3.10-3.69 (n=56), 3.70-4.29 (n=64)
      and 4.30-7.10 (n=59) for FT3; 4.9-14.8 (n=57), 14.9-16.8 (n=58), 16.9-18.7 (n=57)
      and 18.8-29.0 (n=59) for FT4. Subjects with a high FT3 level had significantly
      lower values of INR than those with a low FT3 level (P=0.01). Multiple linear
      regression analysis revealed decreased serum FT3 as an independent risk factor
      for elevated INR values (beta=-0.139, P=0.025). The value of INR was similar
      among the 4 groups according to the quartile FT4 levels (P=0.36). CONCLUSION:
      Free triiodothyronine was negatively associated with INR in the patients with
      acute STEMI and normal thyroid function.

PMID- 21963895
TI  - Yeast two-hybrid screening of proteins interacting with plasmin receptor subunit:
      C-terminal fragment of annexin A2.
AB  - AIM: To identify proteins that interact with the C-terminal fragment of annexin
      A2 (A2IC), generated by plasmin cleavage of the plasmin receptor, a
      heterotetramer (AA2t) containing annexin A2. METHODS: The gene that encodes the
      A2IC fragment was obtained from PCR-amplified cDNA isolated from human monocytes,
      and was ligated into the pBTM116 vector using a DNA ligation kit. The resultant
      plasmid (pBTM116-A2IC) was sequenced with an ABI PRISM 310 Genetic Analyzer. The
      expression of an A2IC bait protein fused with a LexA-DNA binding domain (BD) was
      determined using Western blot analysis. The identification of proteins that
      interact with A2IC and are encoded in a human monocyte cDNA library was performed
      using yeast two-hybrid screening. The DNA sequences of the relevant cDNAs were
      determined using an ABI PRISM BigDye terminator cycle sequencing ready reaction
      kit. Nucleotide sequence databases were searched for homologous sequences using
      BLAST search analysis (http://www.ncbi.nlm.nih.gov). Confirmation of the
      interaction between the protein LexA-A2IC and each of cathepsin S and SNX17 was
      conducted using a small-scale yeast transformation and X-gal assay. RESULTS: The
      yeast transformed with plasmids encoding the bait proteins were screened with a
      human monocyte cDNA library by reconstituting full-length transcription factors
      containing the GAL4-active domain (GAL4-AD) as the prey in a yeast two-hybrid
      approach. After screening 1*10(7) clones, 23 independent beta-Gal-positive clones
      were identified. Sequence analysis and a database search revealed that 15 of
      these positive clones matched eight different proteins (SNX17, ProCathepsin S,
      RPS2, ZBTB4, OGDH, CCDC32, PAPD4, and actin which was already known to interact
      with annexin A2). CONCLUSION: A2IC A2IC interacts with various proteins to form
      protein complexes, which may contribute to the molecular mechanism of monocyte
      activation induced by plasmin. The yeast two-hybrid system is an efficient
      approach for investigating protein interactions.

PMID- 21963896
TI  - Pharmacokinetics of tacrolimus converted from twice-daily formulation to once
      daily formulation in Chinese stable liver transplant recipients.
AB  - AIM: To evaluate the pharmacokinetics of tacrolimus in Chinese stable liver
      transplant recipients converted from immediate release (IR) tacrolimus-based
      immunosuppression to modified release (MR) tacrolimus-based immunosuppression.
      METHODS: Open-label, multi-center study with a one-way conversion design was
      conducted. Eighty-three stable liver recipients (6-24 months post-transplant)
      with normal renal and stable hepatic function were converted from IR tacrolimus
      twice-daily treatment to MR tacrolimus once-daily treatment on a 1:1 (mg: mg)
      total daily dose basis. Twenty-four hour pharmacokinetic studies were carried out
      on d 0 (pre-conversion), d 1, and d 84 (post-conversion). RESULTS: The area under
      the blood concentration-time curve of MR tacrolimus from 0 to 24 h (AUC(0-24)) on
      d 1 was comparable to that of IR tacrolimus on d 0, with a 90% confidence
      interval (CI) for MR/IR tacrolimus of 92%-97%. The AUC(0-24) value for MR
      tacrolimus on d 84 with the daily dose increased by 14% was approximately 17%
      lower than that for IR tacrolimus. The 90% CI was 77%-90%, outside the
      bioequivalence range of 80%-125%. There was a good correlation between AUC(0-24)
      and concentration at 24 h (C(24)) for IR tacrolimus (d 0, r=0.930) and MR
      tacrolimus (d 1, r=0.936; d 84, r=0.903). CONCLUSION: The exposure to tacrolimus
      when administered MR tacrolimus once daily is not equivalent to that for IR
      tacrolimus twice daily after an 84-day conversion in Chinese stable liver
      transplant recipients. The dose should be adjusted on the basis of trough levels.
      The therapeutic drug monitoring for patients treated with IR tacrolimus is
      considered to be applicable to MR tacrolimus.

PMID- 21963897
TI  - Regulation of angiotensin-(1-7) and angiotensin II type 1 receptor by telmisartan
      and losartan in adriamycin-induced rat heart failure.
AB  - AIM: To investigate the possible effects of telmisartan and losartan on cardiac
      function in adriamycin (ADR)-induced heart failure in rats, and to explore the
      changes in plasma level of angiotensin-(1-7)[Ang-(1-7)] and myocardial expression
      of angiotensin II type 1/2 receptors (AT(1)R / AT(2)R) and Mas receptor caused by
      the two drugs. METHODS: Male Sprague-Dawley rats were randomly divided into 4
      groups: the control group, ADR-treated heart failure group (ADR-HF), telmisartan
      plus ADR-treated group (Tel+ADR) and losartan plus ADR-treated group (Los+ADR).
      ADR was administrated (2.5 mg/kg, ip, 6 times in 2 weeks). The rats in the
      Tel+ADR and Los+ADR groups were treated orally with telmisartan (10 mg/kg daily
      po) and losartan (30 mg/kg daily), respectively, for 6 weeks. The plasma level of
      Ang-(1-7) was determined using ELISA. The mRNA and protein expression of
      myocardial Mas receptor, AT(1)R and AT(2)R were measured using RT-PCR and Western
      blotting, respectively. RESULTS: ADR significantly reduced the plasma level of
      Ang-(1-7) and the expression of myocardial Mas receptor and myocardial AT(2)R,
      while significantly increased the expression of myocardial AT(1)R. Treatment with
      telmisartan and losartan effectively increased the plasma level of Ang-(1-7) and
      suppressed myocardial AT(1)R expression, but did not influence the expression of
      Mas receptor and AT(2)R. CONCLUSION: The protective effects of telmisartan and
      losartan in ADR-induced heart failure may be partially due to regulation of
      circulating Ang-(1-7) and myocardial AT(1)R expression.

PMID- 21963899
TI  - Beat-to-beat Ca(2+)-dependent regulation of sinoatrial nodal pacemaker cell rate
      and rhythm.
AB  - Whether intracellular Ca(2+) regulates sinoatrial node cell (SANC) action
      potential (AP) firing rate on a beat-to-beat basis is controversial. To directly
      test the hypothesis of beat-to-beat intracellular Ca(2+) regulation of the rate
      and rhythm of SANC we loaded single isolated SANC with a caged Ca(2+) buffer, NP
      EGTA, and simultaneously recorded membrane potential and intracellular Ca(2+).
      Prior to introduction of the caged Ca(2+) buffer, spontaneous local Ca(2+)
      releases (LCRs) during diastolic depolarization were tightly coupled to rhythmic
      APs (r2=0.9). The buffer markedly prolonged the decay time (T50) and moderately
      reduced the amplitude of the AP-induced Ca(2+) transient and partially depleted
      the SR load, suppressed spontaneous diastolic LCRs and uncoupled them from AP
      generation, and caused AP firing to become markedly slower and dysrhythmic. When
      Ca(2+) was acutely released from the caged compound by flash photolysis,
      intracellular Ca(2+) dynamics were acutely restored and rhythmic APs resumed
      immediately at a normal rate. After a few rhythmic cycles, however, these effects
      of the flash waned as interference with Ca(2+) dynamics by the caged buffer was
      reestablished. Our results directly support the hypothesis that intracellular
      Ca(2+) regulates normal SANC automaticity on a beat-to-beat basis.

PMID- 21963898
TI  - Berberine protects against lipopolysaccharide-induced intestinal injury in mice
      via alpha 2 adrenoceptor-independent mechanisms.
AB  - AIM: To investigate the mechanisms responsible for the protective action of
      berberine (Ber) against gut damage in endotoxemic mice. METHODS: Male BALB/c mice
      were administered intragastrically with distilled water (0.1 mL/10 g), Ber (50
      mg/kg) alone, yohimbine (2 mg/kg) alone, or Ber (50 mg/kg) in combination with
      yohimbine (2 mg/kg) for 3 d. On the third day, lipopolysaccharide (LPS, 18 mg/kg)
      or normal saline was intraperitoneally injected one hour after the intragastric
      administration. Following the treatment, intestinal injury in the ileum was
      histopathologically accessed; enterocyte apoptosis was examined using TUNEL
      method; Toll-like receptor 4 (TLR4) mRNA expression was measured using RT-PCR
      assay; inhibitor protein-kappaBalpha (I-kappaBalpha) phosphorylation and
      myeloperoxidase content were examined using Western blloting. The macrophage
      inflammatory protein-2 (MIP-2) production was measured using ELISA assay.
      RESULTS: Mice challenged with LPS caused extensive ileum injury, including a
      significantly increased injury score, decreased intestinal villus height, reduced
      gut mucosal weight and increased intestinal permeability. Furthermore, LPS
      significantly induced enterocyte apoptosis, increased TLR4 mRNA expression, I
      kappaBalpha phosphorylation, MIP-2 production and myeloperoxidase content in the
      ileum. Pretreatment with Ber significantly alleviated all the alterations in the
      ileum in the endotoxemic mice. Pretreatment with the alpha2-adrenoceptor
      antagonist yohimbine did not block the protective action of Ber against LPS
      induced intestinal injury. In addition, treatment with yohimbine alone did not
      prevent LPS-induced intestinal injury. CONCLUSION: Pretreatment with Ber provides
      significant protection against LPS-induced intestinal injury in mice, via
      reducing enterocyte apoptosis, inhibiting the TLR4-nuclear factor kappaB-MIP-2
      pathway and decreasing neutrophil infiltration that are independent of alpha2
      adrenoceptors.

PMID- 21963901
TI  - Methane yield from switchgrass and reed canarygrass grown in Eastern Canada.
AB  - Methane yields from silage made from switchgrass- and reed canarygrass-seeded
      plots with two N application rates and three harvest dates were assessed in
      Eastern Canada. The average specific methane yield from reed canarygrass-seeded
      plots (0.187 NL CH4 g VS(-1)) was less than from switchgrass-seeded plots (0.212
      NL CH4 g VS(-1)). Switchgrass did not establish well and made up only a small
      proportion of the DM yield. As a consequence, the average methane yield per
      hectare from reed canarygrass-seeded plots (1.37 GL CH4 ha(-1)) was significantly
      greater than switchgrass-seeded plots (0.91 GL CH4 ha(-1)). Increased N
      fertilization reduced specific methane yields but increased methane yield per
      hectare, primarily because of increased DM yield. Delaying harvest resulted in
      decreased methane yields per hectare and specific methane yields, particularly
      for reed canarygrass. Further long-term research could help identify important
      factors influencing methane yields from crops during a complete stand life cycle.

PMID- 21963900
TI  - Continuous flow membrane-less air cathode microbial fuel cell with spunbonded
      olefin diffusion layer.
AB  - The power production performance of a membrane-less air-cathode microbial fuel
      cell was evaluated for 53 days. Anode and cathode electrodes and the micro-fiber
      cloth separator were configured by sandwiching the separator between two
      electrodes. In addition, the air-facing side of the cathode was covered with a
      spunbonded olefin sheet instead of polytetrafluoroethylene (PTFE) coating to
      control oxygen diffusion and water loss. The configuration resulted in a low
      resistance of about 4Omega and a maximum power density of 750 mW/m2. However, as
      a result of a gradual decrease in the cathode potential, maximum power density
      decreased to 280 mW/m2. The declining power output was attributed to loss of
      platinum catalyst (8.26%) and biomass growth (38.44%) on the cathode. Coulombic
      efficiencies over 55% and no water leakage showed that the spunbonded olefin
      sheet covering the air-facing side of the cathode can be a cost-effective
      alternative to PTFE coating.

PMID- 21963902
TI  - Integrated generation of solid fuel and biogas from green cut material from
      landscape conservation and private households.
AB  - Green cut material is a potential source of renewable energy which is not fully
      exploited through conventional energy recovery systems. A new energy conversion
      process, the integrated generation of solid fuel and biogas from biomass (IFBB),
      which includes mechanical separation after hydro-thermal conditioning, was
      investigated. Ash softening temperature and lower heating value of the solid fuel
      were increased through the IFFB process in comparison to the untreated raw
      material. The net energy yield of IFBB at 40  degrees C conditioning temperature
      ranged between 1.96 and 2.85 kWh kg(-1) dry matter (DM) and for the direct
      combustion between 1.75 and 2.65 kWh kg(-1) DM. Conversion efficiencies for the
      IFBB system were 0.42-0.68 and for direct combustion 0.42-0.63. The IFBB system
      produces storable energy from material which is nowadays not used for energy
      conversion.

PMID- 21963903
TI  - Influence of Pleurotus ostreatus inoculation on wood degradation and fungal
      colonization.
AB  - The influence of Pleurotus ostreatus inoculation on wood degradation and on
      fungal community structure was studied. The experiments were performed on an
      organically poor fly ash deposit covered with a 10 cm layer of beech wood chips
      inoculated with P. ostreatus isolate ZIM76. Compared to non-inoculated wood
      chips, inoculation increased the temperatures and relative humidities and, in the
      first 6 months, accelerated Klason lignin degradation by 9% and also, after 17
      months, increased iron translocation into wood chips by 30%. After 6 months, PCR
      DGGE showed 22-28 and 13-21 fungal taxa in non-inoculated and P. ostreatus
      inoculated beech chips, respectively. The differences in number of taxa and in
      the fungal community structure (based on Dice coefficient) between non-inoculated
      and inoculated wood chips diminished with time. The results indicate that the
      naturally occurring processes of wood degradation are as efficient as those
      occurring in sites inoculated with P. ostreatus.

PMID- 21963904
TI  - Anaerobic biodegradation of ethylthionocarbamate by the mixed bacteria under
      various electron acceptor conditions.
AB  - Biodegradation behavior and kinetics of ethylthionocarbamate under nitrate,
      sulfate and ferric reducing conditions by mixed cultures enriched from the
      anaerobic digester sludge was investigated. The results showed that
      ethylthionocarbamate could be degraded independently by the mixed cultures
      coupled to nitrate, sulfate, and ferric reduction, and meanwhile, nitrite,
      sulfide, and ferrous were accumulated as a result of nitrate, sulfate and ferric
      reduction, respectively. Ferric was a more favorable terminal electron acceptor
      compared to nitrate and sulfate. The order of the electron acceptors with
      decreasing biodegradation rates of the ethylthionocarbamate was:
      ferric>nitrate>sulfate, and the corresponding maximum biodegradation rate was
      7.240, 6.267, and 4.602 mg/(L.d), respectively. The anaerobic biodegradation of
      ethylthionocarbamate under various electron acceptor conditions can be accurately
      described by first order exponential decay kinetics.

PMID- 21963905
TI  - Residual biogas potential from the storage tanks of non-separated digestate and
      digested liquid fraction.
AB  - Biogas plants daily produce enormous volumes of digestate that can be handled in
      its raw form or after mechanical separation. In Italy, effluents are usually
      stored within aboveground, uncovered tanks, which make them potential emitters of
      biogas into the atmosphere. The purpose of this study was to estimate the amount
      of biogas emitted to the atmosphere during the storage phase of non-separated
      digestate and digested liquid fraction. The trials were performed at two
      northwest Italy 1 MWel. biogas plants. A floating system for the residual biogas
      recovery, and a set of three wind tunnels for NH3 emission measurement were used.
      The experiment demonstrated significant loss to the atmosphere for each of the
      gases; specifically, on average, 19.5 and 7.90 N m3 biogas MWhel.(-1) were
      emitted daily from the storage tanks of non-separated digestate and digested
      liquid fraction, respectively.

PMID- 21963906
TI  - Robot-assisted laparoscopy in gynecologic surgery.

PMID- 21963907
TI  - Robotic-assisted surgical procedures in visceral and digestive surgery.

PMID- 21963908
TI  - Financial aspects, or how to use robot assistance without losing money.
      Perspectives from a public hospital.

PMID- 21963909
TI  - Angiotensin IV protects against angiotensin II-induced cardiac injury via AT4
      receptor.
AB  - Angiotensin II (Ang II) is an important regulator of cardiac function and injury
      in hypertension. The novel Ang IV peptide/AT4 receptor system has been implicated
      in several physiological functions and has some effects opposite to those of Ang
      II. However, little is known about the role of this system in Ang II-induced
      cardiac injury. Here we studied the effect of Ang IV on Ang II-induced cardiac
      dysfunction and injury using isolated rat hearts, neonatal cardiomyocytes and
      cardiac fibroblasts. We found that Ang IV significantly improved Ang II-induced
      cardiac dysfunction and injury in the isolated heart in response to
      ischemia/reperfusion (I/R). Moreover, Ang IV inhibited Ang II-induced cardiac
      cell apoptosis, cardiomyocyte hypertrophy, and proliferation and collagen
      synthesis of cardiac fibroblasts; these effects were mediated through the AT4
      receptor as confirmed by siRNA knockdown. These findings suggest that Ang IV may
      have a protective effect on Ang II-induced cardiac injury and dysfunction and may
      be a novel therapeutic target for hypertensive heart disease.

PMID- 21963911
TI  - Neuronal network coherent with hand kinematics during fast repetitive hand
      movements.
AB  - We quantified the coupling between magnetoencephalographic (MEG) cortical signals
      and the kinematics of fast repetitive voluntary hand movements monitored by a 3
      axis accelerometer. Ten healthy right-handed adults performed self-paced flexion
      extension movements of right-hand fingers at ~3Hz with either touching the thumb
      during flexions (TOUCH) or not (noTOUCH). At the sensor level, we found in all
      subjects and conditions significant coherence at the movement frequency (F0) and
      its first harmonic (F1). Coherence values were significantly higher in TOUCH
      compared to noTOUCH. At the group level, dynamic imaging of coherent sources
      localized the main source of coherent activity at the left primary motor (M1)
      hand area, except at F0 TOUCH were the main source was localized at the left
      primary sensory (S1) hand area. Other coherent brain areas were also identified
      at right S1-M1 cortices (F0), left dorsolateral prefrontal cortex (F1), left
      posterior parietal cortex (F0 TOUCH and F1 noTOUCH) and left medial S1-M1 areas
      (TOUCH). This study highlights the prominent role of rhythmic neuronal activity
      phase-locked to movements for the encoding and the integration of key sensori
      motor features of limb kinematics. This study also suggests that somatosensory
      afferences play a key role to sustain a high synchronization level between the
      neuronal activity in coherent brain areas and hand acceleration. Some coherent
      brain regions differed between F0 and F1 in both conditions, suggesting that
      distinct cortical areas are involved in different features of hand kinematics.

PMID- 21963910
TI  - Performance-based connectivity analysis: a path to convergence with clinical
      studies.
AB  - Connectivity analyses have become increasingly important in functional imaging.
      When used to describe the functional anatomy of a specific behavior, these
      analyses are generally applied to a subset of the data that demonstrate
      significant differences when experimental conditions are contrasted. Such data
      reduction is sub-optimal for a systems approach as it assumes that all data that
      survive the statistical contrast filter are related to the behavior and that none
      of the filtered data has a significant function. When such data filtering is
      applied to speech and language tasks, the resulting functional anatomy rarely
      reflects the brain lateralization established in over a century and a half of
      clinical studies. A two-step performance-based connectivity analysis is described
      in which the first step uses multiple linear regression to establish a direct
      relationship between regional brain activity and a measure of performance. The
      second step uses partial correlations to examine the functional relationships
      between the predictor regions and other brain regions. When applied to regional
      cerebral blood flow data obtained with positron emission tomography during a
      speech production task, the results demonstrate left lateralization of motor
      control areas, thalamic involvement in repetition rate, and auditory cortical
      suppression, all consistent with clinical observations. The integration of
      performance measures into the earliest stages of image analysis without reliance
      on data filtering based on decomposition may provide a path toward convergence
      with traditional descriptions of functional anatomy based on clinical studies.

PMID- 21963912
TI  - The saccadic spike artifact in MEG.
AB  - Electro- and magnetoencephalography (EEG/MEG) are the means to investigate the
      dynamics of neuronal activity non-invasively in the human brain. However, both
      EEG and MEG are also sensitive to non-neural sources, which can severely
      complicate the interpretation. The saccadic spike potential (SP) at saccade onset
      has been identified as a particularly problematic artifact in EEG because it
      closely resembles synchronous neuronal gamma band activity. While the SP and its
      confounding effects on EEG have been thoroughly characterized, the corresponding
      artifact in MEG, the saccadic spike field (SF), has not been investigated. Here
      we provide a detailed characterization of the SF. We simultaneously recorded MEG,
      EEG, gaze position and electrooculogram (EOG). We compared the SF in MEG for
      different saccade sizes and directions and contrasted it with the well-known SP
      in EEG. Our results reveal a saccade amplitude and direction dependent,
      lateralized saccadic spike artifact, which was most prominent in the gamma
      frequency range. The SF was strongest at frontal and temporal sensors but unlike
      the SP in EEG did not contaminate parietal sensors. Furthermore, we observed that
      the source configurations of the SF were comparable for regular and miniature
      saccades. Using distributed source analysis we identified the sources of the SF
      in the extraocular muscles. In summary, our results show that the SF in MEG
      closely resembles neuronal activity in frontal and temporal sensors. Our detailed
      characterization of the SF constitutes a solid basis for assessing possible
      saccadic spike related contamination in MEG experiments.

PMID- 21963913
TI  - Activation likelihood estimation meta-analysis revisited.
AB  - A widely used technique for coordinate-based meta-analysis of neuroimaging data
      is activation likelihood estimation (ALE), which determines the convergence of
      foci reported from different experiments. ALE analysis involves modelling these
      foci as probability distributions whose width is based on empirical estimates of
      the spatial uncertainty due to the between-subject and between-template
      variability of neuroimaging data. ALE results are assessed against a null
      distribution of random spatial association between experiments, resulting in
      random-effects inference. In the present revision of this algorithm, we address
      two remaining drawbacks of the previous algorithm. First, the assessment of
      spatial association between experiments was based on a highly time-consuming
      permutation test, which nevertheless entailed the danger of underestimating the
      right tail of the null-distribution. In this report, we outline how this previous
      approach may be replaced by a faster and more precise analytical method. Second,
      the previously applied correction procedure, i.e. controlling the false discovery
      rate (FDR), is supplemented by new approaches for correcting the family-wise
      error rate and the cluster-level significance. The different alternatives for
      drawing inference on meta-analytic results are evaluated on an exemplary dataset
      on face perception as well as discussed with respect to their methodological
      limitations and advantages. In summary, we thus replaced the previous permutation
      algorithm with a faster and more rigorous analytical solution for the null
      distribution and comprehensively address the issue of multiple-comparison
      corrections. The proposed revision of the ALE-algorithm should provide an
      improved tool for conducting coordinate-based meta-analyses on functional imaging
      data.

PMID- 21963914
TI  - Birth weight and gestation influence striatal morphology and motor response in
      normal six-year-old boys.
AB  - The relation between fetal growth and attention deficit hyperactivity disorder
      (ADHD) cuts across the normal range of birth weights suggesting that subtle
      variations in fetal development may influence brain and cognitive function. We
      investigated the relation of ADHD-related endophenotypes, such as the striatum
      morphology, motor response and inhibition, with birth weight and gestational age
      in healthy children. 157 Six-year-old boys born at term (37 to 41 weeks) within
      the normal range for birth weight (2500 to 4630 g) underwent magnetic resonance
      imaging (MRI) and performed the stop signal task. Linear regression was used to
      examine effects of birth weight, gestational age, and their interaction on
      striatal volumes and shapes as well as motor response and inhibition. Interactive
      effects of birth weight and gestational age, even within the normal range,
      predicted caudate volumes and shapes. Boys with relatively low birth weight and
      shorter gestation had smaller caudate volumes, reflected by shape contraction in
      the middle body, and in addition performed worst in motor response, reflected by
      mean reaction time and its variability. Our results supported the idea that
      prenatal influences on neurocognitive and brain development are not limited to
      the extreme range, but occur across the entire population. Variations in brain
      structure and cognitive endophenotypes associated with childhood ADHD
      psychopathology are sensitive to subtle prenatal influences, which provides
      guidance for intervention research to improve mental health of children.

PMID- 21963916
TI  - Dynamic Bayesian network modeling for longitudinal brain morphometry.
AB  - Identifying interactions among brain regions from structural magnetic-resonance
      images presents one of the major challenges in computational neuroanatomy. We
      propose a Bayesian data-mining approach to the detection of longitudinal
      morphological changes in the human brain. Our method uses a dynamic Bayesian
      network to represent evolving inter-regional dependencies. The major advantage of
      dynamic Bayesian network modeling is that it can represent complicated
      interactions among temporal processes. We validated our approach by analyzing a
      simulated atrophy study, and found that this approach requires only a small
      number of samples to detect the ground-truth temporal model. We further applied
      dynamic Bayesian network modeling to a longitudinal study of normal aging and
      mild cognitive impairment--the Baltimore Longitudinal Study of Aging. We found
      that interactions among regional volume-change rates for the mild cognitive
      impairment group are different from those for the normal-aging group.

PMID- 21963915
TI  - Specific cerebellar regions are related to force amplitude and rate of force
      development.
AB  - The human cerebellum has been implicated in the control of a wide variety of
      motor control parameters, such as force amplitude, movement extent, and movement
      velocity. These parameters often covary in both movement and isometric force
      production tasks, so it is difficult to resolve whether specific regions of the
      cerebellum relate to specific parameters. In order to address this issue, the
      current study used two experiments and SUIT normalization to determine whether
      BOLD activation in the cerebellum scales with the amplitude or rate of change of
      isometric force production or both. In the first experiment, subjects produced
      isometric pinch-grip force over a range of force amplitudes without any
      constraints on the rate of force development. In the second experiment, subjects
      varied the rate of force production, but the target force amplitude remained
      constant. The data demonstrate that BOLD activation in separate sub-areas of
      cerebellar regions lobule VI and Crus I/II scales with both force amplitude and
      force rate. In addition, BOLD activation in cerebellar lobule V and vermis VI was
      specific to force amplitude, whereas BOLD activation in lobule VIIb was specific
      to force rate. Overall, cerebellar activity related to force amplitude was
      located superior and medial, whereas activity related to force rate was inferior
      and lateral. These findings suggest that specific circuitry in the cerebellum may
      be dedicated to specific motor control parameters such as force amplitude and
      force rate.

PMID- 21963917
TI  - [18F]FDOPA uptake in the raphe nuclei complex reflects serotonin transporter
      availability. A combined [18F]FDOPA and [11C]DASB PET study in Parkinson's
      disease.
AB  - Brain uptake of [(18)F]FDOPA, measured with PET, reflects the activity of
      aromatic amino acid decarboxylase, an enzyme largely expressed in monoaminergic
      nerve terminals. This enzyme catalyzes a number of decarboxylation reactions
      including conversion of l-dopa into dopamine and 5-hydroxytryptophan into
      serotonin. For more than 20years [(18)F]FDOPA PET has been used to assess
      dopaminergic nigrostriatal dysfunction in patients with Parkinson's disease (PD).
      More recently, however, [(18)F]FDOPA PET has also been employed as a marker of
      serotoninergic and noradrenergic function in PD patients. In this study, we
      provide further evidence in support of the view that [(18)F]FDOPA PET can be used
      to evaluate the distribution and the function of serotoninergic systems in the
      brain. Eighteen patients with PD were investigated with both [(18)F]FDOPA and
      [(11)C]DASB PET, the latter being a marker of serotonin transport (SERT)
      availability. We then assessed the relationship between measurements of the two
      tracers within brain serotoninergic structures. [(18)F]FDOPA uptake in the median
      raphe nuclei complex of PD patients was significantly correlated with SERT
      availability in the same structure. Trends towards significant correlations
      between [(18)F]FDOPA Ki values and [(11)C]DASB binding values were also observed
      in the hypothalamus and the anterior cingulate cortex, suggesting a
      serotoninergic contribution to [(18)F]FDOPA uptake in these regions. Conversely,
      no correlations were found in brain structures with mixed dopaminergic,
      serotoninergic and noradrenergic innervations, or with predominant dopaminergic
      innervation. These findings provide evidence that [(18)F]FDOPA PET represents a
      valid marker of raphe serotoninergic function in PD and supports previous studies
      where [(18)F]FDOPA PET has been used to assess serotoninergic function in PD.

PMID- 21963918
TI  - Anatomical insights into disrupted small-world networks in schizophrenia.
AB  - Schizophrenia is characterized by lowered efficiency in distributed information
      processing, as indicated by research that identified a disrupted small-world
      functional network. However, whether the dysconnection manifested by the
      disrupted small-world functional network is reflected in underlying anatomical
      disruption in schizophrenia remains unresolved. This study examined the
      topological properties of human brain anatomical networks derived from diffusion
      tensor imaging in patients with schizophrenia and in healthy controls. We
      constructed the weighted brain anatomical network for each of 79 schizophrenia
      patients and for 96 age and gender matched healthy subjects using diffusion
      tensor tractography and calculated the topological properties of the networks
      using a graph theoretical method. The topological properties of the patients'
      anatomical networks were altered, in that global efficiency decreased but local
      efficiency remained unchanged. The deleterious effects of schizophrenia on
      network performance appear to be localized as reduced regional efficiency in hubs
      such as the frontal associative cortices, the paralimbic/limbic regions and a
      subcortical structure (the left putamen). Additionally, scores on the Positive
      and Negative Symptom Scale correlated negatively with efficient network
      properties in schizophrenia. These findings suggest that complex brain network
      analysis may potentially be used to detect an imaging biomarker for
      schizophrenia.

PMID- 21963919
TI  - Event-related fMRI in cognition.
AB  - A primary advantage of functional magnetic resonance imaging (fMRI) over other
      techniques in neuroscience is its flexibility. Researchers have used fMRI to
      study a remarkable diversity of topics, from basic processes of perception and
      memory, to the complex mechanisms of economic decision making and moral
      cognition. The chief contributor to this experimental flexibility-indeed, to the
      growth of fMRI itself-has been the development of event-related experimental
      designs and associated analyses. The core idea of an event-related design, as
      first articulated in the late 1990s, is the separation of cognitive processes
      into discrete points in time (i.e., "events") allowing differentiation of their
      associated fMRI signals. By modeling brain function as a series of transient
      changes, rather than as an ongoing state, event-related fMRI allowed researchers
      to create much more complex paradigms and more dynamic analysis methods. Yet,
      this flexibility came with a cost. As the complexity of experimental designs
      increased, fMRI analyses became increasingly abstracted from the original data,
      which in turn has had consequences both positive (e.g., greater use of model
      based fMRI) and negative (e.g., fewer articles plot the timing of activation).
      And, as event-related methods have become ubiquitous, they no longer represent a
      distinct category of fMRI research. In a real sense, event-related fMRI has now
      become, simply, fMRI.

PMID- 21963920
TI  - Glucose metabolism of the midline nuclei raphe in the brainstem observed by PET
      MRI fusion imaging.
AB  - The brainstem contains various important monoaminergic neuronal centers,
      including the raphe nuclei which contain serotonergic neurons. The raphe nuclei,
      however, are not easily identifiable and located by conventional neuroimaging.
      METHODS: Fluorodeoxyglucose positron emission tomography (PET) and magnetic
      resonance imaging (MRI) were performed in seven healthy subjects using a new PET
      MRI, which consists of a high-resolution research tomograph (HRRT) PET and 7.0 T
      MRI. Glucose metabolism of raphe nuclei was semiquantitatively measured and
      identified along the midline brainstem region in vivo. RESULTS: Midline nuclei
      clustered in four groups appeared to be the raphe nuclei and could be clearly
      visualized; specifically, we identified the groups as the dorsal raphe, raphe
      reticularis centralis superior, raphe pontis, and raphe magnus group. CONCLUSION:
      FDG imaging of the midline raphe nuclei in vivo could potentially be an important
      tool for investigating brain diseases as well as conducting functional brain
      studies in the context of sleep disorders, depression, and neurodegenerative
      disease.

PMID- 21963921
TI  - Magnetic Resonance Imaging (MRI): keeping abreast of current use?

PMID- 21963922
TI  - Society's expectation of the role of the doctor in New Zealand: results of a
      national survey.
AB  - AIMS: To describe the perceptions of the New Zealand public as to the role of the
      doctor in 2010. METHODS: Telephone survey of 502 individuals throughout New
      Zealand during May 2010. The questions were based on a United Kingdom survey with
      added questions in respect of culture, equity and resource allocation. The data
      were weighted by gender and age according to the 2006 population census. RESULTS:
      Most respondents (82%) wanted to see a doctor first if they had a new concern
      about their health; 7% a nurse and 5% a pharmacist. Most respondents agreed (88%)
      that when visiting a doctor, getting an accurate diagnosis was their top
      priority. In respect of a doctor's personal qualities, integrity was expected
      (94%), as was compassion (89%). Most respondents (78%) agreed that they expected
      a doctor to be the leader of the healthcare team. Most agreed (70%) that there is
      limited money available and doctors must consider how best to use it for all
      patients and that doctors (82%) need to be involved in decisions about health
      spending. CONCLUSION: This comprehensive New Zealand survey provides important
      information about public perceptions of the role of the doctor and is a basis for
      workforce planning and future comparisons.

PMID- 21963923
TI  - Communication difficulties with limited English proficiency patients: clinician
      perceptions of clinical risk and patterns of use of interpreters.
AB  - AIMS: To explore clinicians' perceptions of the communication difficulties
      experienced with Limited English Proficiency (LEP) patients and the clinical
      risks these difficulties pose in hospitals, as well as patterns of interpreter
      use among these clinicians. METHODS: Senior health professionals in the two
      District Health Boards (DHBs) in the Wellington Area (about 900) of New Zealand
      were sent an electronic survey. Twenty clinicians were interviewed about their
      experience in 22 consultations with LEP patients, and an equal number with
      English proficient patients. Descriptive statistics were calculated, and 95%
      confidence intervals and formal statistical tests. RESULTS: 141 responses were
      received to the survey. There was a high level of awareness of how to access
      interpreters (84%) and lesser awareness of DHB interpreter policy (65%). Most
      respondents felt that communication difficulties with LEP patients have a
      significant effect on care at least sometimes, but there is a wide variation in
      reported actual use of interpreters, with only 14% always using an interpreter.
      In the actual consultations studied, no professional interpreters were used
      despite clinician acknowledgement of increased clinical risk. CONCLUSION: Even
      when clinicians are aware of policy, of how to obtain interpreters, and of the
      increased clinical risk in the situation, this does not necessarily lead to high
      levels of interpreter use with LEP patients.

PMID- 21963924
TI  - Improving clinician-patient communication of health risks when diagnostic test
      information is imprecise.
AB  - Both clinicians and patients experience difficulty with the statistical reasoning
      required to make inferences about health states on the basis of information
      derived from diagnostic tests. This problem will grow in importance as we move
      into the era of personalised medicine where an increasing supply of imprecise
      diagnostic tests meets an increasing demand to use such tests on the part of
      intelligent but statistically innumerate clinicians and patients. We describe a
      user-friendly, interactive, graphical interface for calculating, visualising, and
      communicating accurate inferences about uncertain health states when diagnostic
      information (test sensitivity and specificity, and health state prevalence) is
      imprecise and ambiguous in its application to a specific patient. The software is
      free, open-source, and runs on all popular PC operating systems (Windows, Mac,
      Linux).

PMID- 21963925
TI  - Compliance and quality in administration of a Surgical Safety Checklist in a
      tertiary New Zealand hospital.
AB  - AIM: Recent studies have demonstrated a reduction in perioperative complications
      if a surgical safety checklist is utilised. In our institution an adaptation of
      the WHO Surgical Safety Checklist is administered in 3 "domains": on arrival of
      the patient in the operating room (Sign In); before surgical incision (Time Out)
      and before the patients leaves the operating room (Sign Out). Since incomplete
      administration or staff disengagement could diminish any safety benefit we
      evaluated administration of this checklist. METHOD: 100 adult surgical cases were
      observed. Compliance with administration of the Sign In, Time Out, and Sign Out
      domains and their component checklist items was recorded. The timing of the
      checklist administration, and engagement of operating room teams were also
      assessed. RESULTS: The rate (per 100 cases) of the checklist domain
      administration was: 99 for Sign In; 94 for Time Out; and 2 for Sign Out. The mean
      (range) checklist item compliance was 56% (27-100%) for Sign In, 69% (33-100%)
      for Time Out, and 40% for Sign Out. Checklist items related to patient identity
      and surgical procedure were administered in 100% of Sign In administrations.
      Timing of the checklist administration was appropriate in over 80% of cases.
      Engagement by theatre teams was frequently incomplete. CONCLUSION: The Sign Out
      domain was almost always omitted, which may increase the risk of important
      omissions in postoperative care. Most other aspects of checklist administration
      could also be improved. This will require strong leadership from senior
      clinicians in all relevant teams.

PMID- 21963926
TI  - The financial impact of clinical task substitution between practice nurses and
      GPs in New Zealand primary care centres.
AB  - AIM: To describe the financial impact on practice owners of increased clinical
      task substitution between practice nurses and GPs in New Zealand (NZ) primary
      care settings. METHOD: Case studies of 9 primary health care centres involving:
      interviews; collation of service and financial information; and nurse and GP
      diaries covering 1826 consultations. Results were compared with previous NZ large
      N survey results to develop a model predicting the financial impact of task
      substitution. RESULTS: The proportion of general practice primary care
      consultations undertaken by nurses varied from 4% to 46% of total recorded
      consultations. The actual financial impact for a practice owner of substituting
      more nursing time for GP time is highly dependent on the following variables:
      nurse cost per minute relative to GP cost minute; nurse consult duration relative
      to GP consult duration; nurse consult revenue relative to GP consult revenue; and
      the proportion of nurse consults also requiring GP time. CONCLUSION: Practice
      nurses can (and in some practices in NZ, do) provide a broad set of primary care
      services, including undifferentiated general consultations. For some practices,
      increasing the proportion of nurse consults and reducing GP consults, would
      result in significantly improved profitability--for others, the opposite applies.
      Clinical task substitution is one option to address the forecast increase in
      demand associated with population aging.

PMID- 21963927
TI  - Laboratory diagnosis of factitious disorder: a systematic review of tools useful
      in the diagnosis of Munchausen's syndrome.
AB  - AIMS: To assist clinicians in the diagnosis of factitious disorder. METHODS: This
      is a systematic review of the role of laboratory, radiologic, procedural, and
      pathological modalities to assist in the diagnosis of factitious disorder
      (Munchausen's syndrome). The review evaluated 3104 article titles and abstracts
      that were identified from MEDLINE as of January 2010. RESULTS: We found 190
      articles that demonstrated techniques that will assist clinicians in recognizing
      fabricated manifestations of disease. The results are divided into 13 areas of
      clinical medicine for easy reference. They are further sub-divided by the
      diseases or conditions that patients have been reported to simulate and the
      diagnostic techniques suggested by the literature in each case. CONCLUSIONS:
      Factitious disorder is difficult to diagnose and may present as a wide array of
      fabricated conditions, but there are a range of laboratory and technical means
      available to assist clinicians in the 21st Century.

PMID- 21963928
TI  - Imaging of the thyroid gland.
AB  - Incidental and symptomatic pathology of the thyroid gland is common in the
      community. Although technological advances have led to the development and
      improvement of imaging modalities, ultrasound remains the primary diagnostic
      tool. In this article, the authors examine the role of imaging and its recent
      advances in the management of thyroid cancer.

PMID- 21963929
TI  - Encapsulating peritoneal sclerosis--a complication of peritoneal dialysis.
AB  - Encapsulating peritoneal sclerosis (EPS) is a rare complication of peritoneal
      dialysis. It often presents with non-specific symptoms, leading to a delay in
      diagnosis and a poor prognosis. Here we report a case of EPS in a patient treated
      with peritoneal dialysis and discuss the risk factors, diagnostic challenges and
      treatment options available.

PMID- 21963930
TI  - A cerebral mass in a patient with Churg Strauss syndrome.
AB  - BACKGROUND: Differential diagnosis of mass brain lesions with surrounding
      peripheral-ring enhancement includes infections, tumours, demyelinating diseases,
      and vascular lesions such as infarcts or haematomas METHODS: This paper is the
      case report of a 72-year-old Caucasian female patient who presented with a
      subacute onset neurologic deficit and a heterogeneous cerebral mass, an imaging
      finding worrisome for malignancy. CONCLUSION: More specific brain imaging is
      necessary to differentiate between different diseases, especially malignant CNS
      tumours and abscesses. Specific risk factor identification is important but
      cannot replace stereotactic aspiration of pus for accurate microbiologic
      diagnosis and initiation of targeted antimicrobial treatment of cerebral
      abscesses.

PMID- 21963931
TI  - Medical image. Reversible knuckle hyperpigmentation in B12 deficiency.

PMID- 21963932
TI  - Use of pricing and tax interventions for protecting health: potential relevance
      for New Zealand of recent international developments.

PMID- 21963933
TI  - Is integrated academic clinical training needed in New Zealand?

PMID- 21963934
TI  - Acid-responsive microcapsules: the loading-unloading processes.
AB  - A simple and convenient method to prepare acid-responsive microcapsules by using
      functionalized single-walled carbon nanotubes and ytterbium triflate has been
      developed. Fluorescence active compounds were "pre-loaded" or "post-loaded" in
      the microcapsules and released later in acidic medium. An interesting "zip-unzip"
      phenomenon was observed while filming the action of acid on microcapsules under a
      microscope.

PMID- 21963935
TI  - Improved viral suppression after treatment optimization in HIV-infected patients
      with persistent low-level viremia.
AB  - Optimizing treatment for patients with persistent low-level viremia is
      complicated because most genotyping tests are validated for viral loads >1000
      copies per milliliter. In this study, genotypes of 92 treatment-experienced
      patients with persistent low-level viremia were determined using an in-house
      assay. Based on the resistance profiles obtained from genotyping and patient
      pharmacologic history, patients were either maintained on their antiviral regimen
      (n = 51) or received an optimized regimen (n = 41). In the group receiving
      optimized treatment, undetectable viral loads were achieved in 73.2% at 6 months
      and at 90.2% at 1 year, indicating that treatment guided by genotyping of
      patients with low-level viremia is effective in achieving viral suppression.

PMID- 21963937
TI  - Impact of a nurse vaccination program on hepatitis B immunity in a Swiss HIV
      clinic.
AB  - We evaluated the impact of a nurse program for hepatitis B virus vaccination in a
      center from the Swiss HIV Cohort Study. Immunity (anti-HBs >10 IU/mL) increased
      from 32% to 76% in the intervention center (n = 238) where vaccine management was
      endorsed by nurses, but only from 33% to 39% in control centers (n = 2712, P <
      0.001) where management remained in charge of physicians. Immunity against HBV in
      the HIV population is insufficient in Switzerland. Specific nurse vaccination
      program may efficiently improve health care.

PMID- 21963936
TI  - Induction of strong HIV-1-specific CD4+ T-cell responses using an HIV-1
      gp120/NefTat vaccine adjuvanted with AS02A in antiretroviral-treated HIV-1
      infected individuals.
AB  - BACKGROUND: Induction of HIV-1-specific CD4(+) T-cell responses by therapeutic
      vaccination represents an attractive intervention to potentially increase immune
      control of HIV-1. METHODS: We performed a double-blinded, randomized, placebo
      controlled clinical trial to determine the safety and immunogenicity of
      GlaxoSmithKline Biologicals' HIV-1 gp120/NefTat subunit protein vaccine
      formulated with the AS02(A) Adjuvant System in subjects with well-controlled
      chronic HIV-1 infection on highly active antiretroviral therapy. Ten individuals
      received the vaccine; whereas adjuvant alone or placebo was given to 5 subjects
      each. Immunogenicity was monitored by intracellular cytokine flow cytometry and
      carboxyfluorescein succinimidyl ester-based proliferation assays. RESULTS: The
      vaccine was well tolerated with no related serious adverse events. Vaccine
      recipients had significantly stronger gp120-specific CD4(+) T-cell responses
      which persisted until week 48 and greater gp120-specific CD4(+) T-cell
      proliferation activity as compared with controls. In the vaccine group, the
      number of participants who demonstrated positive responses for both gp120
      specific CD4(+) T-cell interleukin-2 production and gp120-specific CD8(+) T-cell
      proliferation were significantly higher at week 6. CONCLUSIONS: The
      gp120/NefTat/AS02(A) vaccine induced strong gp120-specific CD4(+) T-cell
      responses and a higher number of vaccinees developed both HIV-1-specific CD4(+) T
      cell responses and CD8(+) T-cell proliferation. The induction of these responses
      may be important in enhancing immune-mediated viral control.

PMID- 21963938
TI  - Can devices for adult male circumcision help bridge the implementation gap for
      HIV prevention services?
AB  - Medical male circumcision could prevent more than 5 million new HIV infections in
      men in Africa over 20 years and should be a central part of any combination
      prevention public health strategy. Surgical methods, with systems designed for
      high volume services, have been used in circumcision scale-up programs in several
      African countries, but remain limited by the need for high-level health workers,
      skilled in the surgical techniques, and appropriate facilities. New male
      circumcision devices such as the Shang Ring and the PrePex device have shown
      promise in initial trials and may provide innovative ways to improve access to
      medical male circumcision in the future. The rapid introduction of new and
      promising biomedical strategies for HIV prevention, including antiretrovirals for
      HIV prevention, will require early consideration of delivery systems and service
      design.

PMID- 21963940
TI  - Impact of integrated family planning and HIV care services on contraceptive use
      and pregnancy outcomes: a retrospective cohort study.
AB  - OBJECTIVE: To determine the impact of routine care (RC) and integrated family
      planning (IFP) and HIV care service on family planning (FP) uptake and pregnancy
      outcomes. DESIGN: Retrospective cohort study conducted between October 10, 2005,
      and February 28, 2009. SETTING: United States Agency for International
      Development-Academic Model Providing Access To Healthcare (USAID-AMPATH) in
      western Kenya. SUBJECTS: Records of adult HIV-infected women. INTERVENTION:
      Integration of FP into one of the care teams. PRIMARY OUTCOMES MEASURES:
      Incidence of FP methods and pregnancy. RESULTS: Four thousand thirty-one women
      (1453 IFP; 2578 RC) were eligible. Among the IFP group, there was a 16.7%
      increase (P < 0.001) [95% confidence interval (CI): 13.2% to 20.2%] in incidence
      of condom use, 12.9% increase (P < 0.001) (95% CI: 9.4% to 16.4%) in incidence of
      FP use including condoms, 3.8% reduction (P < 0.001) (95% CI: 1.9% to 5.6%) in
      incidence of FP use excluding condoms, and 0.1% increase (P = 0.9) (95% CI: -1.9%
      to 2.1%) in incidence of pregnancies. The attributable risk of the incidence rate
      per 100 person-years of IFP and RC for new condom use was 16.4 (95% CI: 11.9 to
      21.0), new FP use including condoms was 13.5 (95% CI: 8.7 to 18.3), new FP use
      excluding condoms was -3.0 (95% CI: -4.6 to -1.4) and new cases of pregnancies
      was 1.2 (95% CI: -0.6 to 3.0). CONCLUSIONS: Integrating FP services into HIV care
      significantly increased the use of modern FP methods but no impact on pregnancy
      incidence. HIV programs need to consider integrating FP into their program
      structure.

PMID- 21963939
TI  - Outside sexual partnerships and risk of HIV acquisition for HIV uninfected
      partners in African HIV serodiscordant partnerships.
AB  - BACKGROUND: As African countries scale-up couples HIV testing, little is known
      about sexual behaviors and HIV risk for HIV-uninfected partners in known HIV
      serodiscordant relationships. METHODS: We conducted a prospective study of 3380
      HIV-serodiscordant partnerships from 7 African countries. Self-reported sexual
      behavior data were collected quarterly from HIV-uninfected partners. RESULTS: The
      proportion of HIV-uninfected partners reporting sex with their known primary HIV
      infected partner decreased during follow-up (from 93.5% in the prior month at
      baseline to 73.2% at 24 months, P < 0.001). Simultaneously, an increasing
      proportion reported sex with an outside partner (from 3.1% to 13.9%, P < 0.001).
      A small proportion (<5%, stable throughout follow-up) reported sex with the
      infected partner and an outside partner in the same month (concurrent).
      Unprotected sex was more common with outside partners than with their primary
      known HIV-infected partners (risk ratio 4.6; 95% confidence interval: 4.2 to
      5.2). HIV incidence was similar for those reporting sex only with their primary
      HIV-infected partner compared with those who reported an outside partner (2.87
      vs. 3.02 per 100 person-years, P = 0.7), although those who had outside partners
      were more likely to acquire HIV that was virologically distinct from that of
      their primary partner (P < 0.001). CONCLUSION: For uninfected members of HIV
      serodiscordant couples, sex with the infected partner declined as sex with
      outside partners increased, likely reflecting relationship dissolution and risk
      shifting from a known infected partner. Risk-reduction messages for HIV
      uninfected partners in serodiscordant partnerships should include strategies to
      reduce HIV acquisition from outside partners.

PMID- 21963941
TI  - Urinary lipoarabinomannan as predictor for the tuberculosis immune reconstitution
      inflammatory syndrome.
AB  - BACKGROUND: Upon initiation of antiretroviral therapy (ART), 15.7% [95%
      confidence interval (CI): 9.7% to 24.5%] of tuberculosis (TB)-HIV-coinfected
      individuals experience paradoxical worsening of their clinical status with
      exuberant inflammation consistent with immune reconstitution inflammatory
      syndrome (IRIS). We investigated whether a positive urinary TB lipoarabinomannan
      (LAM) antigen enzyme-linked immunosorbent assay test before ART initiation was
      associated with development of paradoxical TB-IRIS. METHODS: In a prospective
      observational cohort in Mulago Hospital, Kampala, Uganda, we measured pre-ART
      urinary LAM concentrations in HIV-infected patients on TB treatment. Patients who
      developed TB-IRIS (according to the International Network for the Study of HIV
      associated IRIS case definition) were compared with patients who remained IRIS
      free for at least 3 months. RESULTS: Twenty-six individuals with TB-IRIS and 64
      without IRIS were included in the analysis. The median time to TB-IRIS was 14
      days (interquartile range: 11-14 days). Univariate analysis showed that a
      positive pre-ART urinary LAM test [OR: 4.6 (95% CI: 1.5 to 13.8), P = 0.006] and
      a CD4 count <50 cells/mL [OR: 21 (95% CI: 2.6 to 169.4), P = 0.004] were
      associated with an increased risk of TB-IRIS. In multivariate analysis, only a
      baseline CD4 T-cell count <50 cells/mL was predictive of IRIS (P < 0.004).
      Sensitivity and specificity of a positive pre-ART urinary LAM test to diagnose
      IRIS were 80.8% (95% CI: 60.6 to 93.4) and 52.4% (95% CI: 39.4 to 65.1),
      respectively. CONCLUSIONS: If CD4 T-cell count testing is available, a pre-highly
      active antiretroviral therapy urinary LAM test has no added value to predict TB
      IRIS. When CD4 T-cell count is not available, a positive LAM test could identify
      patients at increased risk of TB-IRIS.

PMID- 21963942
TI  - Lack of the detection of XMRV or polytropic MLV-related sequences in blood cells
      from HIV-1-infected patients in Spain.
AB  - BACKGROUND: Xenotropic murine leukemia virus-related virus (XMRV) and polytropic
      murine leukemia virus (MLV)-related virus are recently described human
      gammaretroviruses that have been associated with prostate cancer and chronic
      fatigue syndrome. These studies have been controversial because a number of
      laboratories have been unable to find evidence of XMRV in similar groups of
      patients or controls. Because the existence of XMRV raises many questions, we
      decided to study its presence in a group of patients infected with HIV-1 with a
      high proportion of intravenous drug use and coinfection by hepatitis C virus.
      METHODS: Forty HIV-1-infected patients under follow-up in our institution were
      screened for XMRV/MLV by nested polymerase chain reaction using primers targeting
      the gag and env region. Specific primers for mouse mitochondrial DNA were used to
      rule out contamination. RESULTS: No evidence of XMRV or polytropic MLV-related
      sequences was found in any sample from patients or controls. Four samples yielded
      polymerase chain reaction bands whose sequence corresponded to murine endogenous
      retroviral sequences, however, contamination with mouse cell DNA was subsequently
      confirmed. CONCLUSIONS: XMRV/MLV viruses do not seem to be associated with HIV-1
      infection or intravenous drug use. Contamination of samples or reagents by
      genomic murine DNA or XMRV vectors could account for the sporadic detection of
      positive samples for XMRV and related agents.

PMID- 21963943
TI  - Development of a serodiagnostic test for sheep scab using recombinant protein Pso
      o 2.
AB  - Early stages of sheep scab, the disease caused by the non-burrowing mite
      Psoroptes ovis, are often sub-clinical, or can be mis-diagnosed. A diagnostic
      test capable of detecting early disease and latent infestations is therefore
      highly desirable in disease control. This paper describes the design and
      validation of an ELISA, which incorporates a recombinant P. ovis antigen (Pso o
      2), for the early detection of anti-P. ovis serum antibodies in sheep. This ELISA
      was evaluated using sera from sheep infested with P. ovis (n = 58) and sheep (n =
      433) with no P. ovis infestation as well as sheep infected with other parasites
      including gastrointestinal nematodes (GIN), or chewing lice. A receiver operating
      characteristic (ROC) curve analysis was generated using the ELISA results for 491
      sheep sera with the area under the curve (AUC) being 0.97. An optimal OD(450) cut
      off of >0.06 absorbance units gave a test sensitivity of 0.93 and specificity of
      0.90. The Pso o 2-based ELISA was able to detect specific antibodies to P. ovis
      during early experimental infestation prior to disease patency, indicating its
      utility for detecting sub-clinical infestation.

PMID- 21963944
TI  - Characterization of Micrococcus strains isolated from indoor air.
AB  - The characterization of microbes, such as opportunists and pathogens (e.g.,
      methicillin resistant Staphylococcus aureus [MRSA]), in indoor air is important
      for understanding disease transmission from person-to-person. Common genera found
      in the human skin microbiome include Micrococcus and Staphylococcus, but there
      only a limited number of tests to differentiate these genera and/or species. Both
      genera are believed to be released into indoor air from the shedding of human
      skin and are morphologically difficult to distinguish. In the current work, after
      the extraction of proteins from micrococci and the separation of these proteins
      on one dimensional electrophoretic gels, tryptic peptides were analyzed by MALDI
      TOF MS and the mass profiles compared with those of a reference strain (ATCC
      4698). The results confirmed that all strains were consistent in identity with
      Micrococcus luteus.

PMID- 21963945
TI  - The involvement of RGS9 in l-3,4-dihydroxyphenylalanine-induced dyskinesias in
      unilateral 6-OHDA lesion rat model.
AB  - Chronic dopamine (DA) replacement therapy with L-3,4-dihydroxyphenylalanine (L
      DOPA) in Parkinson's disease (PD) often leads to abnormal involuntary movements
      (AIMs) known as L-DOPA-induced dyskinesia (LID), mediated by DA receptors.
      However, mechanisms underlying LID occurrence are still unclear. Regulator of G
      protein signaling RGS9, a member of the RGS family of GTPase accelerating
      proteins, is expressed specifically in the striatum, has been reported
      participated in LID. L-DOPA-induced AIMs can be modeled in rats with 6
      hydroxydopamine (6-OHDA) lesions by chronic injection of L-DOPA. Herein, we
      compared the rotational responses and AIMs in 6-OHDA lesioned rats with L
      DOPA/benserazide (10/2.5 mg/kg, once per day, i.p.) administration for 14 days
      whereas control animals received injections of saline. Furthermore, whether sub
      chronic L-DOPA treatment impact RGS9 mRNA or protein expression in 6-OHDA lesion
      rats were also evaluated. As results shown, rotational behavior was not increased
      significantly, while an obvious AIMs were observed in rats with L
      DOPA/benserazide (10/2.5mg/kg, i.p.) administration sub-chronically. In addition,
      expressions of RGS9 protein or mRNA analyzed by Western blot or real-time PCR
      with striatal extracts increased significantly after L-DOPA/benserazide. These
      data demonstrate that RGS9 expression can be modulated by sub-chronic L
      DOPA/benserazide administration and increased RGS9 expression in striatum may be
      one of the reasons for the side effects such as dyskinesia induced by L-DOPA
      therapy.

PMID- 21963947
TI  - Regulation of CCL2/MCP-1 production in astrocytes by desipramine and atomoxetine:
      involvement of alpha2 adrenergic receptors.
AB  - Having previously observed that noradrenaline activation of beta adrenergic
      receptors induces the synthesis of the chemokine monocyte chemoattractant protein
      (CCL2/MCP-1) in astrocytes, it is our interest to analyze the mechanisms involved
      in this process, particularly the possible effect of noradrenaline-modulating
      drugs. The treatment of primary rat astrocyte cultures with the noradrenaline
      transporter inhibitors desipramine or atomoxetine induced the expression and
      synthesis of CCL2/MCP-1 in these cells. This effect of both drugs in vitro
      suggests that CCL2/MCP-1 expression could also be modulated by some mechanism
      independent of the elevation of brain noradrenaline levels. This was confirmed by
      measuring a reduction in CCL2/MCP-1 production by the treatment with the alpha2
      adrenergic receptor agonist clonidine. Accordingly, the blockade of alpha2
      adrenergic receptors with yohimbine potentiated the production of MCP-1
      stimulated by the activation of beta receptors. While the activation of beta
      adrenergic receptors and the subsequent elevation of cAMP levels seem to be the
      main pathway for noradrenaline to induce CCL2/MCP-1 in astrocytes, our data
      indicate that the alpha2 adrenergic receptors also regulate CCL2/MCP-1 expression
      working as inhibitory mediators.

PMID- 21963948
TI  - Hypothermia down-regulates the LPS-induced norepinephrine (NE) release in
      ischaemic human heart cells.
AB  - Hypothermia has been widely acknowledged as the fundamental component of
      myocardial protection during cardiac operations. In this work, we studied in
      human atrial tissue the effect of the common hypothermic protection used in
      cardiac surgery, and we assessed this effect by comparing catecholamine release
      among normoxic, ischaemic, and inflammatory conditions. Our results provide the
      first evidence that lipopolysaccharide treatment results in an extremely dramatic
      and significant increase in the resting norepinephrine release under ischaemic
      conditions that can be normalised by hypothermia. These findings demonstrate that
      inflammatory conditions increase the temperature sensitivity of the
      norepinephrine transporter in human cardiac tissue. When the possible
      pharmacological interventions are taken into consideration, the results presented
      here provide new insight into the protection against ischaemia/reperfusion injury
      during cardiac surgery.

PMID- 21963946
TI  - The interhemispheric connections of the striatum: Implications for Parkinson's
      disease and drug-induced dyskinesias.
AB  - Parkinson's disease (PD) is characterized by loss of nigrostriatal neurons and
      depletion of dopamine. This pathological feature leads to alterations to basal
      ganglia circuitry and subsequent motor disability. Pharmacological dopamine
      replacement therapy with medications such as levodopa ameliorates the symptoms of
      PD but can lead to motor complications known as drug-induced dyskinesias. We have
      recently shown that clinically hemiparkinsonian rhesus monkeys do not develop
      levodopa-induced dyskinesias despite chronic intermittent exposure and
      significant unilateral loss of nigrostriatal neurons and dopamine. It is
      currently unclear what mechanisms prevent the onset of dyskinesias in these
      animals. Based on our study and results from previous lesioning studies in both
      the rat and monkey models of PD, we hypothesize that one potential mechanism that
      may prevent the genesis of dyskinesias in these animals is interhemispheric
      neuromodulation. Two potential interhemispheric connections that may modulate
      dyskinesias are the interhemispheric nigrostriatal and corticostriatal pathways.
      Few investigators have examined the interhemispheric nigrostriatal and
      corticostriatal connections and the functional role they may play in drug-induced
      dyskinesias in PD. Therefore, in the following review, we assess the
      neuroanatomical, electrophysiological and behavioral properties of these
      interhemispheric connections. Future studies evaluating these interhemispheric
      striatal pathways and the pathophysiological changes that occur to these pathways
      in the dyskinetic state are warranted to further develop treatments that prevent
      or mitigate drug-induced dyskinesias in PD.

PMID- 21963949
TI  - High efficiency human memory B cell assay and its application to studying
      Plasmodium falciparum-specific memory B cells in natural infections.
AB  - Memory B cells (MBCs) are a key component of long term humoral immunity to many
      human infectious diseases. Despite their importance, we know little about the
      generation or maintenance of antigen-(Ag)-specific MBCs in humans in response to
      infection. A frequently employed method for quantifying Ag-specific MBCs in human
      peripheral blood (Crotty et al., 2004) relies on the ability of MBCs but not
      naive B cells to differentiate into antibody secreting cells (ASCs) in response
      to polyclonal activators and Toll-like receptor agonists in vitro and the
      measurement of Ag-specific ASCs by ELISPOT assays. Here we report on studies to
      optimize the efficiency of this ELISPOT-based assay and to apply this assay to
      the detection of Plasmodium falciparum (Pf)-specific MBCs in adults living in a
      malaria endemic area where immunity to Pf is acquired through natural infection.
      We show that the addition of IL-10 to in vitro cultures of human peripheral blood
      mononuclear cells increased the efficiency of the assay from 10% to over 90%
      without increasing the ASC burst size and without any substantial increase in
      background from naive B cells or plasma cells (PCs). Using this assay we were
      able to quantify the frequency of Pf-specific MBCs in peripheral blood of adults
      living in a malaria endemic area. Thus, this highly efficient assay appears to be
      well suited to field studies of the generation and maintenance of MBCs where the
      volumes of blood obtainable are often limiting.

PMID- 21963951
TI  - Propolis protects against 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced toxicity in
      rat hepatocytes.
AB  - The present experiment was undertaken to determine the effectiveness of propolis
      in alleviating the toxicity of TCDD on cultured primary rat hepatocytes. Propolis
      (25, 50 and 100 MUM) was added to plain culture or simultaneously with TCDD (5
      and 10 MUM). The hepatocytes were treated with TCDD and propolis for 48 h. Then
      cell viability was detected by [3-(4,5-dimethyl-thiazol-2-yl) 2,5
      diphenyltetrazolium bromide] (MTT) assay and lactate dehydrogenase (LDH) release,
      while total antioxidant capacity (TAC) and total oxidative stress (TOS) levels
      were determined to evaluate the oxidative injury. The DNA damage was also
      analyzed by liver micronucleus assay (LMN) and 8-oxo-2-deoxyguanosine (8-OH-dG).
      The results of MTT and LDH assays showed that TCDD decreased cell viability. TCDD
      also increased TOS level and decreased TAC level in rat hepatocytes. On the basis
      of increasing doses, the TCDD caused significant increases of micronucleated
      hepatocytes (MNHEPs) and 8-OH-dG levels as compared to control culture. In
      cultures treated with propolis alone, cell viability and TOS level were not
      affected, while the level of TAC was significantly increased in dose-dependent
      fashion. The presence of propolis with TCDD modulated its toxic effects on
      primary hepatocytes cultures. Noteworthy, propolis has a protective effect
      against TCDD-mediated DNA damages.

PMID- 21963950
TI  - A new antigen scanning strategy for monitoring HIV-1 specific T-cell immune
      responses.
AB  - Delineation of the immune correlates of protection in natural infection or after
      vaccination is a mandatory step for vaccine development. Although the most recent
      techniques allow a sensitive and specific detection of the cellular immune
      response, a consensus on the best strategy to assess their magnitude and breadth
      is yet to be reached. Within the AIDS Vaccine Integrated Project (AVIP
      http://www.avip-eu.org) we developed an antigen scanning strategy combining the
      empirical-based approach of overlapping peptides with a vast array of database
      information. This new system, termed Variable Overlapping Peptide Scanning Design
      (VOPSD), was used for preparing two peptide sets encompassing the candidate HIV-1
      vaccine antigens Tat and Nef. Validation of the VOPSD strategy was obtained by
      direct comparison with 15mer or 20mer peptide sets in a trial involving six
      laboratories of the AVIP consortium. Cross-reactive background responses were
      measured in 80 HIV seronegative donors (HIV-), while sensitivity and magnitude of
      Tat and Nef-specific T-cell responses were assessed on 90 HIV+ individuals. In
      HIV-, VOPSD peptides generated background responses comparable with those of the
      standard sets. In HIV-1+ individuals the VOPSD pools showed a higher sensitivity
      in detecting individual responses (Tat VOPSD vs. Tat 15mers or 20mers: p<=0.01)
      as well as in generating stronger responses (Nef VOPSD vs. Nef 20mers: p<0.001)
      than standard sets, enhancing both CD4 and CD8 T-cell responses. Moreover, this
      peptide design allowed a marked reduction of the peptides number, representing a
      powerful tool for investigating novel HIV-1 candidate vaccine antigens in cohorts
      of HIV-seronegative and seropositive individuals.

PMID- 21963952
TI  - Alterations in protein metabolism and amino acid concentrations in rats fed by a
      high-protein (casein-enriched) diet - effect of starvation.
AB  - Rats were fed with a standard laboratory diet (SLD) or a high-protein diet (HPD).
      After three months changes in amino acid concentration and protein metabolism
      were examined in fed and 24h-fasted animals. In the blood of the HPD animals
      sacrificed in fed state were found higher concentrations of urea, aspartate,
      taurine, proline, valine, isoleucine, and leucine, and lower concentrations of
      glycine and cysteine. The main alterations in tissues were decreased
      concentrations of glycine and increased concentrations of valine, isoleucine, and
      leucine. Differences in weight, protein concentration, protein synthesis, and
      proteolysis in tissues were insignificant. The exception was soleus muscle in
      which higher values of protein synthesis and proteolysis were found in HPD
      animals. The response to starvation of HPD and SLD fed animals was different. In
      animals fed before starvation by HPD was found more pronounced decrease in a
      number of individual amino acids in plasma and tissues and more pronounced
      decrease in protein synthesis in muscle, spleen, jejunum, and colon. It is
      concluded that chronic intake of HPD has not positive effect on protein balance
      in any tissue, results in the imbalance in aminoacidemia in extracellular and
      intracellular fluid, and alters the response of the organism to starvation.

PMID- 21963953
TI  - Hypolipidemic and anti-inflammatory properties of Abacopterin A from Abacopteris
      penangiana in high-fat diet-induced hyperlipidemia mice.
AB  - This study was to investigate the hypolipidemic and anti-inflammatory properties
      of Abacopterin A (APA), a flavonoid compound isolated from Abacopteris penangiana
      (Hook.) Ching. Male C57BL/6J mice were divided randomly and equally into five
      groups: the normal control group (N), the model group (M), the positive control
      group (P), the high and low doses of APA treated groups (H and L). All the
      animals except that in N group were fed with high-fat diet for 8 weeks. In the
      last 4 weeks, the mice in P, H and L groups were orally administered with
      simvastatin (at the dose of 20mg/kg/day) and APA (at the dose of 40 or
      20mg/kg/day), respectively. Then the lipid profiles and related biochemical
      criterions of the studied mice were determined. The effects of high-fat diet on
      activating nuclear transcription factor-kappaB (NFkappaB) expression, elevating
      inflammatory factors tumor necrosis factor-alpha (TNF-alpha) and interleukin-6
      (IL-6) levels, and increasing triacylglycerol (TG) and total cholesterol (TC)
      levels were abolished on daily supplementation with APA. APA also enhanced
      lipoprotein lipase (LPL) and hepatic lipase (HL) activities. These results
      suggested that APA had hypolipidemic and anti-inflammatory properties through
      inhibiting NFkappaB expression, and reducing inflammatory response.

PMID- 21963954
TI  - Influence of Cu supplementation on toxic and essential trace element status in
      intensive reared beef cattle.
AB  - The aim of this study is to evaluate if dietary Cu supplementation that leads to
      a hepatic Cu accumulation over the normal range has an influence on trace element
      status that could contribute to the pathogenesis of other mineral related
      disorders. Samples (liver, kidney, spleen, diaphragm and brain) of beef calves
      receiving typical commercial diets Cu supplemented and non-supplemented were
      tested for differences in non-essential and essential trace elements determined
      by ICP-MS. As (kidney and diaphragm), Hg (liver and kidney), and Pb (liver,
      kidney and spleen) were significantly lower, while Cd residues (liver and kidney)
      were significantly higher in the Cu supplemented group. Mn and Ni significantly
      decreased and Mo increased in the brain, and Se (diaphragm) decreased in the Cu
      supplemented group. These interactions are unknown, and possibly with more than
      two metals involved as suggested in the case of the ratio Se:Cu in the animals of
      this study. The possible role of Cu supplementation on the status of certain
      metals associated to neurological diseases (Mn-Ni) in the brain deserves further
      investigation. Finally new research on Cu-Se supplementation is necessary to
      better understand the risk of the animals to suffer from Se deficiency.

PMID- 21963955
TI  - Lower incidence of biliary carcinoma in patients with primary sclerosing
      cholangitis and high serum levels of immunoglobulin E.
AB  - BACKGROUND & AIMS: High serum levels of immunoglobulin (Ig)E often are detected
      in patients with primary sclerosing cholangitis (PSC), but the clinical
      significance is not known. METHODS: We analyzed data from 44 patients with PSC
      and known serum levels of IgE. They were divided into groups called high IgE
      (>170 IU/mL; n = 17) or normal IgE (n = 27). We compared occurrence of biliary
      carcinoma including cholangiocellular and gallbladder carcinoma, liver
      transplantation, and death between groups. RESULTS: The high IgE group had a
      later age of onset of PSC than the normal IgE group (54 +/- 20 y vs 39 +/- 16 y;
      P = .010); they also had a higher serum level of IgG (2078 +/- 638 vs 1517 +/-
      475 mg/dL; P = .002) and IgG4 (104 +/- 102 vs 38 +/- 16 mg/dL; P = .002).
      Association with inflammatory bowel disease did not differ significantly between
      groups (5 of 17 vs 11 of 27; P = .661). No patient had biliary carcinoma in the
      high IgE group, but biliary carcinoma was observed during the follow-up period in
      8 patients in the normal IgE group (0 of 17 vs 8 of 27; P = .016). The occurrence
      of biliary carcinoma, liver transplantation, or death did not differ between
      groups (4 of 17 vs 13 of 27; P = .124). CONCLUSIONS: High serum levels of IgE
      often are observed in older patients with PSC and are associated with a reduced
      incidence of biliary carcinoma.

PMID- 21963956
TI  - Antimicrobial antibodies are associated with a Crohn's disease-like phenotype
      after ileal pouch-anal anastomosis.
AB  - BACKGROUND & AIMS: Pouchitis and Crohn's disease (CD)-like (CDL) complications of
      the pouch occur at rates near 50% and 20%, respectively, after colectomy with
      ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). We investigated
      whether antimicrobial antibodies are associated with pouch outcome after IPAA.
      METHODS: We studied clinical and endoscopic data from 399 individuals with UC who
      underwent colectomy with IPAA at Mount Sinai Hospital in Toronto, Canada;
      patients were classified as no pouchitis (NP), chronic pouchitis (CP), or CDL.
      Serum samples were analyzed from 341 patients for antibodies against
      Saccharomyces cerevisiae (ASCA), OmpC, CBir1, and perinuclear antineutrophil
      cytoplasmic antibody (pANCA). RESULTS: Of the subjects, 70.7% had NP, 16.8%
      developed CP, and 12.5% developed CDL. Smoking was associated with CDL (P =
      .003). Ashkenazi Jewish individuals more commonly had CP (P = .008). Of patients
      with CDL, 53.5% and 14.0% had positive test results for anti-CBir1 and ASCA
      (immunoglobulin G), respectively, compared with 21.4% and 3.8% of those with NP
      and 28.3% and 5.0% of those with CP (P < .0001 and P = .03). Anti-CBir1 was
      associated with CDL, compared with NP (P = 2.8 * 10(-5); odds ratio [OR], 4.2;
      95% confidence interval [CI], 2.2-8.3) or CP (P = .011; OR, 2.9; 95% CI, 1.3
      6.6). ASCA immunoglobulin G was associated with CDL, compared with patients with
      NP (P = .01; OR, 4.1; 95% CI, 1.4-12.3). In a combined model, pANCA and the
      antimicrobial antibodies were associated with CP (P = .029) and CDL (P = 4.7 *
      10(-4)). CONCLUSIONS: Antimicrobial antibodies and pANCA are associated with
      inflammatory complications of the pouch. The CDL phenotype is associated with
      factors that characterize Crohn's disease, including smoking, anti-CBir1, and
      ASCA.

PMID- 21963957
TI  - Efficacy of an artificial neural network-based approach to endoscopic ultrasound
      elastography in diagnosis of focal pancreatic masses.
AB  - BACKGROUND & AIMS: By using strain assessment, real-time endoscopic ultrasound
      (EUS) elastography provides additional information about a lesion's
      characteristics in the pancreas. We assessed the accuracy of real-time EUS
      elastography in focal pancreatic lesions using computer-aided diagnosis by
      artificial neural network analysis. METHODS: We performed a prospective, blinded,
      multicentric study at of 258 patients (774 recordings from EUS elastography) who
      were diagnosed with chronic pancreatitis (n = 47) or pancreatic adenocarcinoma (n
      = 211) from 13 tertiary academic medical centers in Europe (the European EUS
      Elastography Multicentric Study Group). We used postprocessing software analysis
      to compute individual frames of elastography movies recorded by retrieving hue
      histogram data from a dynamic sequence of EUS elastography into a numeric matrix.
      The data then were analyzed in an extended neural network analysis, to
      automatically differentiate benign from malignant patterns. RESULTS: The neural
      computing approach had 91.14% training accuracy (95% confidence interval [CI],
      89.87%-92.42%) and 84.27% testing accuracy (95% CI, 83.09%-85.44%). These results
      were obtained using the 10-fold cross-validation technique. The statistical
      analysis of the classification process showed a sensitivity of 87.59%, a
      specificity of 82.94%, a positive predictive value of 96.25%, and a negative
      predictive value of 57.22%. Moreover, the corresponding area under the receiver
      operating characteristic curve was 0.94 (95% CI, 0.91%-0.97%), which was
      significantly higher than the values obtained by simple mean hue histogram
      analysis, for which the area under the receiver operating characteristic was
      0.85. CONCLUSIONS: Use of the artificial intelligence methodology via artificial
      neural networks supports the medical decision process, providing fast and
      accurate diagnoses.

PMID- 21963958
TI  - Adverse events do not outweigh benefits of combination therapy for Crohn's
      disease in a decision analytic model.
AB  - BACKGROUND & AIMS: The Study of Biologic and Immunomodulator-Naive Patients With
      Crohn's Disease (SONIC) showed that combination therapy with infliximab and
      azathioprine (IFX/AZA) is more effective than treatment with IFX alone. Numbers
      and types of adverse events were roughly equivalent among groups, although
      enrollment was limited, so it was not clear how rare adverse events might affect
      overall outcomes in practice. We sought to define the frequency at which a rare
      adverse event would have to occur for the risks of combination therapy to
      outweigh the benefits of treatment. METHODS: We constructed a decision model to
      compare the risks and benefits of IFX/AZA with IFX monotherapy. Model parameters
      were taken from SONIC and other published literature. The base-case analysis was
      patients with active Crohn's disease who are naive to both medications (similar
      to those in SONIC) who were treated for 1 year. We used sensitivity analyses to
      determine the thresholds at which the risks of side effects from IFX/AZA outweigh
      its benefits. RESULTS: During 1 year, the benefits of IFX/AZA would outweigh the
      risks, unless serious infections occurred in 20% or more of the population or
      lymphoma in 3.9% or more. These thresholds are 5-fold and 65-fold higher than
      base-case estimates, respectively. CONCLUSIONS: On the basis of data from 1 year
      of SONIC, the combination of IFX/AZA was more effective than IFX alone in
      patients with Crohn's disease who are naive to either drug. For the risks of
      combination therapy to outweigh the benefits in this time frame, the incidence of
      serious adverse events would have to be higher than seems clinically realistic.

PMID- 21963959
TI  - Long-term outcomes of patients with primary biliary cirrhosis and hepatocellular
      carcinoma.
AB  - BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is an aggressive tumor that
      frequently develops in patients with primary biliary cirrhosis (PBC). We
      determined the mortality of patients with PBC who develop HCC, and which
      interventions (surgery, radiofrequency ablation, chemoembolization, alcohol
      injection, or transplantation) increase survival times. We investigated whether
      the Milan criteria predict outcomes of these patients and are effective in
      selection for liver transplantation. METHODS: We evaluated data from 38 patients
      who had a confirmed diagnosis of PBC and HCC between March 1993 and February
      2011. Patients were grouped based on whether or not they met the Milan criteria.
      Survival was assessed using the Kaplan-Meier analysis. RESULTS: Eighteen of the
      38 patients (47.3%) died during the follow-up period; 49.4% survived for 5 years
      and 31.7% survived for 10 years. Thirty-five patients (92.0%) underwent one or a
      combination of interventions. Liver transplantation improved survival (risk
      ratio, 0.06; P < .0001), whereas surgery approached significance in causing
      deterioration (risk ratio, 2.87; P = .07). Mortality did not appear to be
      affected by meeting the Milan criteria (P = .84). CONCLUSIONS: Five- and 10-year
      survival times for patients with PBC who developed HCC were 49.4% and 31.7%,
      respectively. Patients who meet the Milan criteria receive liver transplantation
      as often as those who do not; we did not observe a difference in survival time
      between groups. Patients with PBC who develop HCC appear to benefit from
      aggressive therapies.

PMID- 21963960
TI  - Integument structure and function in juvenile Xenopus laevis with disrupted
      thyroid balance.
AB  - The skin is the largest organ in the body and is a barrier between the internal
      and external environment. The present study evaluates how PTU, a goitrogen, that
      is used to treat hyperthyroidism affects the structure and electrical properties
      of the frog (Xenopus laevis) skin. The results are considered in the context of
      the two-membrane model established in the seminal work of Ussing and collegues in
      the 1940s and 1950s. In vitro experiments with skin from Xenopus adults revealed
      that PTU can act directly on skin and causes a significant increase (p<0.05, One
      way ANOVA) in short circuit current (Isc) via an amiloride-insensitive mechanism.
      Juvenile Xenopus exposed to waterborne PTU (5 mg/L) had a significantly bigger
      and more active thyroid gland (p<0.01, Student's t-test) than control Xenopus.
      The bioelectric properties of skin taken from Xenopus juveniles treated with PTU
      in vivo had a lower Isc, (3.05+/-0.4, n=13) and Rt (288.2+/-39.5) than skin from
      control Xenopus (Isc, 4.19+/-1.14, n=14; Rt, 343.3+/-43.3). A histological
      assessment of skin from PTU treated Xenopus juveniles revealed the epidermis was
      significantly thicker (p<0.01, Student's t-test) and had a greater number of
      modified exocrine glands (p<0.01, Student's t-test) in the dermis compared to
      control skin. Modifications in skin structure are presumably the basis for its
      changed bioelectric properties and the study highlights a site of action for
      environmental chemicals which has been largely neglected.

PMID- 21963961
TI  - Characterization of testicular expression of P450 17alpha-hydroxylase, 17,20
      lyase in zebrafish and its perturbation by the pharmaceutical fungicide
      clotrimazole.
AB  - The aim of the present study was to characterize P450 17alpha-hydroxylase/17,20
      lyase (cyp17a1) expression in zebrafish and to assess the effect of the
      pharmaceutical clotrimazole, a known inhibitor of various cytochrome P450 enzyme
      activities, on testicular gene and protein expression of this enzyme as well as
      on the testicular release of 11-ketotestosterone (11-KT), a potent androgen in
      fish. We first showed that cyp17a1 is predominantly expressed in gonads of
      zebrafish, notably in male. In vivo, clotrimazole induced a concentration
      dependent increase of cyp17a1 gene expression and Cyp17-I protein synthesis in
      zebrafish testis. Using zebrafish testicular explants, we further showed that
      clotrimazole did not directly affect cyp17a1 expression but that it did inhibit
      11-KT release. These novel data deserve further studies on the effect of azole
      fungicides on gonadal steroidogenesis.

PMID- 21963962
TI  - Optimal method for efficiently removing extracellular nanofilaments from
      Shewanella oneidensis MR-1.
AB  - The identification, production, and potential electron conductivity of bacterial
      extracellular nanofilaments is an area of great study, specifically in Shewanella
      oneidensis MR-1. While some studies focus on nanofilaments attached to the
      cellular body, many studies require the removal of these nanofilaments for
      downstream applications. The removal of nanofilaments from S. oneidensis MR-1 for
      further study requires not only that the nanofilaments be detached, but also for
      the cell bodies to remain intact. This is a study to both qualitatively (AFM) and
      quantitatively (LC/MS-MS) assess several nanofilament shearing methods and
      determine the optimal procedure. The best method for nanofilament removal, as
      judged by maximizing extracellular filamentous proteins and minimizing membrane
      and intracellular proteins, is vortexing a washed cell culture for 10 min.

PMID- 21963963
TI  - Combination of cytochrome b heteroduplex-assay and sequencing for identification
      of triatomine blood meals.
AB  - The identification of blood meals in vectors contributes greatly to the
      understanding of interactions between vectors, microorganisms and hosts. The aim
      of the current work was to complement the validation of cytochrome b (Cytb)
      heteroduplex assay (HDA) previously described, and to add the sequencing of the
      Cytb gene of some samples for the identification of blood meals in triatomines.
      Experimental feedings of reared triatomines helped to clarify the sensitivity of
      the HDA. Moreover, the sequencing coupled with the HDA, allowed the assessment of
      the technique's taxonomic level of discrimination. The primers used to produce
      DNA fragments of Cytb genes for HDA had a very high sensitivity for vertebrate
      DNAs, rather similar for mammals, birds and reptiles. However, the formation of
      heteroduplex depended on blood meal's quality rather than its quantity; a
      correlation was observed between blood meals' color and the positivity of HDA.
      HDA electrophoresis profiles were reproducible, and allowed the discrimination of
      blood origins at the species level. However, in some cases, intraspecific
      variability of Cytb gene generated different HDA profiles. The HDA based on
      comparison of electrophoresis profiles is a very useful tool for screening large
      samples to determine blood origins; the subsequent sequencing of PCR products of
      Cytb corresponding to different HDA profiles allowed the identification of
      species whatever the biotope in which the vectors were captured.

PMID- 21963964
TI  - [Scientific basis of treatment for infectious diseases--appropriate use of
      antibacterial agents based on PK-PD theory].

PMID- 21963965
TI  - [Expectations for the pharmacists in the management of infectious diseases].
AB  - In the 21 century, the management of infectious diseases has become increasingly
      important. Especially, the establishment of the infection prevention and control
      system is very important in the healthcare-settings for patient safety. And from
      this background, infection control teams (ICT) which perform the infectious
      diseases management have been organized in many institutions. These ICT members
      are medical doctors, nurses, medical technologists and pharmacists and the role
      of the pharmacist in the ICT is very important. The pharmacist should play a role
      as a specialist for antimicrobial agents, antiseptics and disinfectants. The
      roles and responsibilities of the pharmacist for infection control are leading
      the antimicrobial stewardship, promoting the appropriate and rational use of
      antimicrobial agents, advising the health system on the selection and use of
      appropriate antiseptics, disinfectants and sterilants, developing guidelines for
      risk assessment, treatment, and monitoring of patients and health care workers.
      Establishing internal pharmacy policies, procedures and quality control programs
      to prevent contamination, educating health professionals, patients, and the
      public activity are also included. It is expected that the infection control
      pharmacist should contribute to the management of infectious diseases and patient
      safety in the healthcare-settings.

PMID- 21963966
TI  - [Optimization of antimicrobial therapy based on therapeutic drug monitoring].
AB  - Recently, the pharmacokinetic (PK)-pharmacodynamic (PD) theory draws attention in
      the therapy of the infectious disease. Although the theory was only introduced
      into the field of antimicrobial therapy several years ago, the foundation was in
      the individualization of administering design by therapeutic drug monitoring
      (TDM) begun 30 years ago. Although, the main purpose of TDM that had been
      performed so far was assumption of the evasion of the side effects caused with
      antimicrobials, it is difficult to say that it has been used as a tool to improve
      the efficacies. Furthermore, although the information described in the package
      inserts of antimicrobials must be important grounds to use the agents properly,
      it was recently recognized that there were pitfalls in PK-PD region. In this
      review, the following three items are described; 1) problem of dosage regimen
      described in package insert of antimicrobials, such as aminoglycosides and
      vancomycin in our country, and findings accumulated through their TDM; 2)
      strategy for proper use of antimicrobials based on PK-PD theory; 3) finally, the
      role of the pharmacist expected in the area of the infectious disease treatment.

PMID- 21963967
TI  - [Appropriate antibiotic use for the respiratory tract infections].
AB  - Early appropriate antibiotic treatment is vital since respiratory tract infection
      (RTI) is a potentially fatal disease. Therefore, the Japanese Respiratory Society
      (JRS) provided four guidelines for the management of RTI in adults. The basic
      policy and main purposes of the JRS guidelines include; 1) prevention of
      bacterial resistance and 2) effective and long-term use of medical resources. The
      JRS guidelines have recommended the exclusion of potential and broad spectrum
      antibiotics from the list of first-choice drugs for empirical treatment. In
      addition, the JRS guidelines have recommended short-term usage of antibiotics of
      an appropriate dose.

PMID- 21963968
TI  - [Safety profile of antimicrobial agents].
AB  - Many antibiotics have been developed and used for the treatment of infectious
      diseases. Although they have been known to have various adverse effects, most of
      the mechanisms remain still unknown. New quinolones are well known to induce
      convulsions and their convulsant activity enhanced by concurrent administration
      of anti-inflammatory drugs. Each new quinolone has an individual convulsant
      activity with individual drug-interaction with anti-inflammatory drugs. And
      enoxacin, lomefloxacin and gatifloxacin have been reported to decrease blood
      glucose levels in a dose-depend- ent manner, but ciprofloxacin and levofloxacin
      had no effect on the levels. It should be important to know the safety profile of
      antimicrobial agents before doctors administer these agents to the patients with
      infectious diseases.

PMID- 21963969
TI  - [Development and validation of programs for ligand-binding-pocket search].
AB  - Searching for the ligand-binding pockets of proteins plays an important role in
      structure-based drug design (SBDD), which is based on knowledge of the three
      dimensional structures of target proteins. In SBDD, small molecules that can
      interact with the target protein are designed. SBDD methods require the
      identification of ligand-binding pockets, in which ligand molecules interact with
      protein atoms. The computer programs for the detection of ligand-binding pockets
      are categorized into two types: one is programs using only geometric properties;
      and the other is programs using the physicochemical properties of proteins as
      well as geometry. This paper describes the development and evaluation of a
      program for ligand-binding pocket search. The program HBOP (Hydropho Bicity On a
      Protein) searches for ligand-binding pockets using hydrophobic potentials derived
      from experimentally determined functions. This is based on the fact that
      hydrophobicity plays a significant role in protein-ligand binding. The results of
      evaluation indicate that programs using physicochemical properties can discover
      actual ligand-binding pockets more efficiently than those using only geometric
      properties.

PMID- 21963970
TI  - [Intramolecular cyclization reaction of multiple bonds and its application].
AB  - The cycloaddition and cycloisomerization of the allene with an alkyne, alkene, or
      an additional allene for construction of various monocyclic and bicyclic ring
      systems has been developed. The characteristic features of these methods using
      allene functionality instead of a simple alkene or alkyne include the reaction
      mode that originated from the double function as well as the high efficiency for
      the constructions of medium-sized rings. Furthermore, asymmetric formal synthesis
      of (+)-nakadomarin A and total synthesis of (+)-fawcettimine and (+)
      lycoposerramine-B based on highly stereoselective Pauson-Khand reaction of alkene
      alkynes were completed.

PMID- 21963971
TI  - [Blood-brain barrier transport of opioid analgesics].
AB  - Opioid analgesics exhibit cationic properties under physiological conditions, and
      the mechanism underlying permeation of the blood-brain barrier thus cannot be
      fully explained by simple diffusion alone. Various types of transporters that
      exhibit substrate specificity are localized on the blood-brain barrier, and play
      a role in transporting substances from circulating blood and from brain
      interstitial fluid. Progress is being made in explaining the mechanisms,
      functions, and physiological roles of polyspecific organic cation transporters,
      but little evidence has indicated that these previously identified organic cation
      transporters are involved in the transport of opioid analgesics across the blood
      brain barrier. Consequently, clarifying the role of transporters in the
      distribution of opioid analgesics into the brain and determining their transport
      molecule will not only provide clues to effective drug delivery to the brain, but
      will also contribute to optimizing pain relief treatment, and by extension play a
      role in drug discovery for analgesics. Currently there are enthusiastic
      discussions in the literature regarding the existence of putative transporters
      involved in the transport of opioid analgesics across the blood-brain barrier.
      This review article introduces the results of our research as well as recent
      findings on the involvement of transporters in the blood-brain barrier transport
      of opioid analgesics such as morphine, morphine metabolites, oxycodone, fentanyl,
      codeine, and pentazocine.

PMID- 21963972
TI  - [Development of environmentally benign transformations via 1,3-transposition of
      hydroxyl group].
AB  - This review article describes our recent efforts to develop environmentally
      benign transformations of allyl and propargyl alcohols via the 1,3-transposition
      of their hydroxyl groups using combined catalyst systems. This methodology allows
      for successful transformation under mild conditions, which has never been
      achieved using each catalyst. Representative examples of this methodology include
      the following three reactions. First, the combination of oxo-vanadium compounds
      and lipases resulted in the dynamic kinetic resolution of racemic allyl alcohols
      to give optically active allyl esters in high yields. Second, Mo-Au-Ag
      combination catalysis dramatically accelerated the rearrangement of diverse
      propargyl alcohols into alpha,beta-unsaturated carbonyl compounds. Finally, the
      choice of suitable heteropoly acids for the rearrangement of propargyl alcohols
      led to the selective preparation of both (Z)- and (E)-enones.

PMID- 21963973
TI  - [Role of RecQ5 in syncytial blastoderm of the Drosophila embryo].
AB  - RecQ5 belongs to the family of RecQ DNA helicases. There are 5 RecQ homologs in
      mammals, and defects in 3 of them (BLM, WRN, and RECQL4) give rise to cancer
      predisposition syndromes in humans. Although no human disease has yet been
      genetically linked to a mutation in RecQ5, this enzyme is thought to have unique
      functions, based on its ubiquitous expression profile and specific C-terminal
      amino acid sequence, both of which are very different from those of other RecQ
      DNA helicase family members. The analysis of MEF and ES cells derived from RecQ5
      deficient mice investigated by Hu et al. suggested an important role for RecQ5 in
      the DNA metabolism of the early embryo. However, it is unknown how RecQ5
      deficiency destabilizes DNA. To address the DNA instabilities in RecQ5-deficient
      animals, we chose Drosophila melanogaster which has simple checkpoint systems in
      its syncytial embryos. By analyzing Drosophila syncytial embryos, we demonstrated
      that the loss of RecQ5 increased the frequency of spontaneous mitotic defects
      such as anaphase bridge formation. A pair of daughter nuclei that had been linked
      by such DNA bridges was simultaneously eliminated via a Chk2-dependent pathway.
      These findings suggest that the lack of RecQ5 causes spontaneous double-strand
      DNA breaks. RecQ5 may thus function in the resolution of anaphase DNA bridges
      during mitosis in syncytial embryo.

PMID- 21963974
TI  - Effects of novel all-trans retinoic acid retinamide derivatives on the
      proliferation and apoptosis of human lung adenocarcinoma cell line A549 cells.
AB  - The aim of the present study was to synthesize a series of retinamide derivatives
      using all-trans retinoic acid (ATRA) as raw material and observe their effects on
      the differentiation and apoptosis of human lung adenocarcinoma A549 cells. Four
      new synthesized ATRA retinamide derivatives were structurally confirmed by
      spectral analysis, including (1)H-NMR, (13)C-NMR, and MS. The results showed that
      the new ATRA retinamide derivatives significantly decreased the carcinoembryonic
      antigen secretion of A549 cells, significantly decreased the proliferation of
      A549 cells in a dose- and time-dependent manner, and promoted the apoptosis of
      A549 cells compared with ATRA. The Western blot assay indicated that the
      expression of Bcl-2 was decreased more in A549 cells treated with N-(3
      trifluoromethylphenyl) retinamide than that in A549 cells treated with ATRA. The
      results also showed that the effects of N-(3-trifluoromethyl-phenyl) retinamide
      on differentiation and apoptosis were the strongest among the newly synthesized
      ATRA retinamide derivatives. Our results suggested that the effects of novel ATRA
      retinamide derivatives on increasing the differentiation, decreasing the
      proliferation, and promoting the apoptosis of A549 cells were greater than those
      of ATRA. The apoptosis of A549 cells induced by N-(3-trifluoromethylphenyl)
      retinamide may be related to downregulating the expression of Bcl-2.

PMID- 21963975
TI  - [Chemopreventive effects of 5-fluorouracil and lactoferrin on goldfish intestinal
      carcinogenesis induced by 1,2-dimethylhydrazine].
AB  - The present study was carried out to examine the chemopreventive effects of 5
      fluorouracil (5-FU) and lactoferrin (LF) on goldfish intestinal carcinogenesis
      induced by 1,2-dimethylhydrazine (DMH). DMH was given to fish by intraperitoneal
      injection in a dosage of 15 mg/kg body weight once a week for 6 weeks. Eight
      weeks after the initial DMH injection, fish were randomly divided into 2 groups,
      control and LF-treated groups. Control fish fed a commercial diet. LF- treated
      fish fed a commercial diet with bovine lactoferrin (oral administration at 200
      mg/kg body weight/day). Ten weeks after the initial DMH injection, each was
      divided into 2 groups, saline- and 5-FU- treated groups. Physiological saline for
      freshwater fish (0.75% NaCl solution) in the saline-treated fish and 5-FU
      dissolved in 0.75% NaCl solution in the 5-FU-treated (75 mg/kg body weight) fish
      were injected intramuscularly three times every other day, respectively. The mean
      number of precancer cell foci (PCF) per intestine was 2.7 in DMH treated fish.
      PCF showed broader distribution in the entire intestine derived from DMH-treated
      fish. LF-only-treatment has no effect on the number of PCF. Mean number of PCF in
      5-FU-only-treated fish decreased in comparison with that of the saline-treated
      control group, though no statistically significant reduction in PCF was found.
      But if 5-FU treatment was added to LF pretreatment, a statistically significant
      reduction in the number of PCF was observed. Pretreatment with LF for 2 weeks
      also reduced the deleterious side effects of 5-FU.

PMID- 21963976
TI  - [Model analysis of tulobuterol patch formulations to explain the influence of
      drug release rate and transdermal transfer rate on the plasma concentration
      profile].
AB  - The purpose of this study was to compare the transdermal transfer profiles of
      brand and generic tulobuterol patch formulations and to evaluate possible changes
      of in vivo kinetics resulting from increased transdermal transfer by means of
      pharmacokinetic analysis using reported in vitro drug release rate data and
      plasma drug concentration profiles. On the assumption that the transdermal
      transfer rate constant (k2) would be constant (independent of formulation), the
      drug release rate constant from patch formulation (k1) was predicted to be almost
      equal to the k2 value (k1~k2) in the brand formulation, but 2- to 4-fold higher
      than the k2 value (k1>k2) in the two generic formulations. Under normal
      conditions, there would be no marked difference in the plasma concentration
      profiles among the formulations. However, under conditions where transdermal
      transfer is increased (that is, higher k2), the plasma tulobuterol concentration
      was predicted to increase more rapidly, with higher C(max), and then to decrease
      more rapidly in the elimination phase after applying the generic formulations
      compared with the brand formulation. These different behaviors would be seen
      because the transdermal transfer of the generic formulations would be affected by
      k2, whereas k1 is still rate-determining for the brand formulation. These results
      suggest that bronchial asthma patients with risk factors for impaired skin
      barrier function, including atopic dermatitis, long-term treatment with steroids,
      and advanced age, should be carefully monitored for reduced treatment efficacy or
      adverse drug reactions after application of rapid-release generic tulobuterol
      patch formulations.

PMID- 21963977
TI  - [Molecular cloning and functional characterization of a novel gene encoding human
      prostaglandin carrier, hPrC].
AB  - In the present study, we isolated and determined the pharmacological
      characteristics of a novel gene encoding the human prostaglandin carrier (hPrC).
      The isolated cDNA consisted of 1431 base pairs that encoded a 477-amino acid
      protein, and we found that isolated hPrC does not belong to any drug transporter
      families. RT-PCR analysis revealed that the hPrC mRNA is expressed in various
      human tissues ubiquitously. When expressed in Xenopus laevis oocytes, hPrC
      mediated the transport of [(3)H]prostaglandin E(2) (PGE(2)) in a sodium
      independent manner. The uptake of [(3)H] PGE(2) was not trans-stimulated by PG
      analogous. Although there are several PG transporters such as multidrug
      resistance-associated protein 4 (MRP4), organic cation transporter 1 (OCT1)
      [solute carrier (SLC) 22A1], organic anion transporter 1-3 (OAT1-3) [SLC22A6-8],
      OAT4 [SLC11], OATP-1 (LST-1) [SLCO1B1], OATP2B1 [SLCO2B1], OATP2A1 (PGT)
      [SLCO2A1], OATP4A1 (OATP-E) [SLCO4A1] have been isolated and well characterized,
      our findings suggest that hPrC functions as a novel transport peptide responsible
      for PG uptake. Our results should provide insight into the novel mechanism of the
      PG transport in the human body.

PMID- 21963978
TI  - [Making tablets of powdered milk and the physical properties].
AB  - Compressed baby milk powder has proven to be very convenient for parents due to
      the ease with which it can be handled, and the fact that use of a measuring scoop
      is not necessary. The purpose of this study was to develop a compressed baby milk
      powder and analyze the resulting physical properties. The basic production
      process consisted of the following steps: 1) molding milk powder by low
      compression pressure, 2) humidification at 25 degrees C.97%RH and 3) drying with
      use of a desiccant. No chemical additives were used for solidification; therefore
      the chemical composition of the compressed milk powder is identical to the base
      milk powder. The important properties of the compressed milk powder are both
      ready solubility and the strength of the solid. The compressed milk powder
      obtained at low pressure was too brittle for practical use, but the strength was
      increased by humidification followed by drying. During the humidification
      process, the powder particles located close to the surface of the compressed milk
      powder partially dissolve resulting in bridging structures between the particles,
      leading to an increase in strength. Both specific surface area and the volume
      ratio of the compressed milk powder decreased. Testing showed that caking between
      the particles occurred following humidification, and that the volume of caking
      affected the ease with which the compressed milk powder dissolves in water.

PMID- 21963979
TI  - [Survey on the awareness of community pharmacists about raising pharmaceutical
      questions regarding prescriptions issued by physicians].
AB  - Community pharmacists can provide effective pharmaceutical care by questioning
      the physicians about their prescriptions. The regulatory authority (Ministry of
      Health, Labour and Welfare or the like) has been issuing instructions/advice to
      health insurance-covered pharmacies about the nature of questions to be asked to
      physicians under the national health insurance system. However, this practice has
      been facing similar kind of problems almost every year. To identify the reasons
      for repetition of the problems and facilitate proper application of drug therapy
      at hospitals, we recently examined the nature of questions asked to physicians by
      conducting a survey of 165 health insurance-covered pharmacies belonging to 8
      district branches of the Japan Pharmaceutical Association. When the pharmacists
      were asked to express their view whether each of the 18 sample questions included
      in the past surveys was actually necessary, the most frequent answer from the
      respondents (n=1980) was "neutral" (42.9%), followed by "unnecessary" (29.0%) and
      "necessary" (26.6%). Further, 55.5% respondents answered that it is necessary to
      refer to publications of the concerned fields (guidelines, etc.) when questioning
      the prescriptions. However, the responses about the possible reasons for judging
      the necessity of the questions suggested that sometimes the pharmacists failed to
      understand the details of such publications. The results from this study suggest
      that a high percentage of community pharmacists believed that there was little
      need to ask questions about prescriptions if the suggestions made by the
      regulatory authority about the relevant questions were taken into account.
      Further, our study findings suggested that pharmacists working at clinics cannot
      present a clear-cut rationale for their judgment about the necessity of asking
      questions about prescriptions under the current circumstances where sufficient
      information collection and the evaluation of need for asking questions about
      prescriptions are not possible.

PMID- 21963980
TI  - [Preparation of liposome using egg yolk].
AB  - In this study, 162 students in the 6 year Pharmacy Program at the School of
      Pharmacy, Iwate Medical University were asked to prepare liposomal preparations
      using chicken egg yolk and to evaluate their properties with the aim of
      developing novel liposomes. High-purity lecithins are generally used for
      preparing liposomes but they are expensive. On the other hand, egg yolk has
      various components, including lecithin and cholesterol, which are important
      components for the formation of liposomes, so it was hypothesized that liposomes
      prepared from egg yolk may participate in the formation of cell membrane in
      chicks. Both liposomes from egg yolk (YL) and from lecithin (LL) exhibited
      Malthesian crosses using a polarizing microscope and multilamellar vesicles were
      observed, confirming that liposomal preparations from egg yolk were useful. The
      particle size of YL was about 100 nm with one peak. Furthermore, the YL are
      believed to be viable under different conditions because the particle size did
      not change when they were prepared in buffers having different pH values. The
      results of these experiments indicate that liposomal preparations from egg yolk
      can serve as natural materials, although some obstacles remain. This is a unique
      approach for carrying out practical training in our 6 year pharmaceutical science
      program.

PMID- 21963981
TI  - Surgical complications of skin sparing mastectomy and immediate prosthetic
      reconstruction after neoadjuvant chemotherapy for invasive breast cancer.
AB  - BACKGROUND: Neoadjuvant chemotherapy is gaining acceptance as an option for
      breast cancer treatment, particularly in young women. These women may seek
      immediate breast reconstruction after mastectomy even though it is not known
      whether such preoperative chemotherapy may be detrimental to post-reconstruction
      wound healing. Therefore, we set out to assess the influence of neoadjuvant
      chemotherapy for invasive breast cancer on the short-term complications after
      skin sparing mastectomy and immediate prosthetic reconstruction. METHODOLOGY: The
      short-term surgical outcome of 48 immediate breast reconstructions in 37 women
      treated with neoadjuvant chemotherapy from 2006 through 2009 was prospectively
      compared to that of 215 immediate reconstructions in 176 women who were operated
      in the same period without neoadjuvant chemotherapy. RESULTS: The overall rate of
      short-term postoperative complications was significantly less among neoadjuvantly
      treated women (15% vs. 29%; p = 0.042) but this did not result in a reduction of
      loss of prostheses (8% vs. 11%; p = 0.566). CONCLUSION: Because neoadjuvant
      chemotherapy is not associated with an increase in short-term complications after
      skin sparing mastectomy and immediate prosthetic reconstruction in patients with
      invasive breast cancer, such combined surgical therapy may be offered as
      treatment option for this particular group of patients also.

PMID- 21963982
TI  - The impact of temperature on balancing immune responsiveness and growth in
      Arabidopsis.
AB  - Plants have evolved polymorphic immune receptors to recognize pathogens causing
      disease. However, triggering of resistance needs to be tuned to the local
      environment to maintain a balance between defense and growth. We consider here
      the impact of temperature as a key environmental factor influencing immune
      pathway activation in Arabidopsis. Genetic compensatory and molecular buffering
      mechanisms affecting the diversification, functionality and subcellular dynamics
      of immune receptors, reveal multiple points at which temperature intersects with
      host resistance signaling systems, including a role of at least one receptor in
      sensing temperature change. Analysis of temperature-dependent autoimmunity caused
      by allelic mismatches in hybrids of evolutionary diverged Arabidopsis accessions
      is illuminating processes by which plants maintain 'poise' between immune
      responsiveness and fitness in natural populations.

PMID- 21963985
TI  - Identification of 4-quinolone derivatives as inhibitors of reactive oxygen
      species production from human umbilical vein endothelial cells.
AB  - Oxidative stress is widely recognized as being associated with a number of
      disorders, including metabolic dysfunction and atherosclerosis. A series of
      substituted 4-quinolone derivatives were prepared and evaluated as inhibitors of
      reactive oxygen species (ROS) production from human umbilical vein endothelial
      cells (HUVECs). One compound in particular, 2-({[4-(3-hydroxy-3
      methylbutoxy)pyridin-2-yl]oxy}methyl)-3-methylquinolin-4(1H)-one (25b), inhibited
      ROS production from HUVECs with an IC(50) of 140 nM. This compound also exhibited
      low CYP2D6 inhibitory activity, high aqueous solubility, and good in vitro
      metabolic stability. An in vivo pharmacokinetic study of this compound in SD rats
      revealed high oral bioavailability and a long plasma half-life.

PMID- 21963983
TI  - Improving peppermint essential oil yield and composition by metabolic
      engineering.
AB  - Peppermint (Mentha * piperita L.) was transformed with various gene constructs to
      evaluate the utility of metabolic engineering for improving essential oil yield
      and composition. Oil yield increases were achieved by overexpressing genes
      involved in the supply of precursors through the 2C-methyl-D-erythritol 4
      phosphate (MEP) pathway. Two-gene combinations to enhance both oil yield and
      composition in a single transgenic line were assessed as well. The most promising
      results were obtained by transforming plants expressing an antisense version of
      (+)-menthofuran synthase, which is critical for adjusting the levels of specific
      undesirable oil constituents, with a construct for the overexpression of the MEP
      pathway gene 1-deoxy-D-xylulose 5-phosphate reductoisomerase (up to 61% oil yield
      increase over wild-type controls with low levels of the undesirable side-product
      (+)-menthofuran and its intermediate (+)-pulegone). Elite transgenic lines were
      advanced to multiyear field trials, which demonstrated consistent oil yield
      increases of up to 78% over wild-type controls and desirable effects on oil
      composition under commercial growth conditions. The transgenic expression of a
      gene encoding (+)-limonene synthase was used to accumulate elevated levels of (+)
      limonene, which allows oil derived from transgenic plants to be recognized during
      the processing of commercial formulations containing peppermint oil. Our study
      illustrates the utility of metabolic engineering for the sustainable agricultural
      production of high quality essential oils at a competitive cost.

PMID- 21963986
TI  - Non-steroidal dissociated glucocorticoid agonists: indoles as A-ring mimetics and
      function-regulating pharmacophores.
AB  - We report a SAR of non-steroidal glucocorticoid mimetics that utilize indoles as
      A-ring mimetics. Detailed SAR is discussed with a focus on improving PR and MR
      selectivity, GR agonism, and in vitro dissociation profile. SAR analysis led to
      compound (R)-33 which showed high PR and MR selectivity, potent agonist activity,
      and reduced transactivation activity in the MMTV and aromatase assays. The
      compound is equipotent to prednisolone in the LPS-TNF model of inflammation. In
      mouse CIA, at 30 mg/kg compound (R)-33 inhibited disease progression with an
      efficacy similar to the 3 mg/kg dose of prednisolone.

PMID- 21963987
TI  - Molecular mechanism of transcription inhibition by phage T7 gp2 protein.
AB  - Escherichia coli T7 bacteriophage gp2 protein is a potent inhibitor of host RNA
      polymerase (RNAP). gp2 inhibits formation of open promoter complex by binding to
      the beta' jaw, an RNAP domain that interacts with downstream promoter DNA. Here,
      we used an engineered promoter with an optimized sequence to obtain and
      characterize a specific promoter complex containing RNAP and gp2. In this
      complex, localized melting of promoter DNA is initiated but does not propagate to
      include the point of the transcription start. As a result, the complex is
      transcriptionally inactive. Using a highly sensitive RNAP beacon assay, we
      performed quantitative real-time measurements of specific binding of the RNAP-gp2
      complex to promoter DNA and various promoter fragments. In this way, the effect
      of gp2 on RNAP interaction with promoters was dissected. As expected, gp2 greatly
      decreased RNAP affinity to downstream promoter duplex. However, gp2 also
      inhibited RNAP binding to promoter fragments that lacked downstream promoter DNA
      that interacts with the beta' jaw. The inhibition was caused by gp2-mediated
      decrease of the RNAP binding affinity to template and non-template strand
      segments of the transcription bubble downstream of the -10 promoter element. The
      inhibition of RNAP interactions with single-stranded segments of the
      transcription bubble by gp2 is a novel effect, which may occur via allosteric
      mechanism that is set in motion by the gp2 binding to the beta' jaw.

PMID- 21963988
TI  - The structures of Thermoplasma volcanium phosphoribosyl pyrophosphate synthetase
      bound to ribose-5-phosphate and ATP analogs.
AB  - Phosphoribosyl pyrophosphate (PRPP) synthetase catalyzes the transfer of the
      pyrophosphate group from ATP to ribose-5-phosphate (R5P) yielding PRPP and AMP.
      PRPP is an essential metabolite that plays a central role in cellular metabolism.
      The enzyme from a thermophilic archaeon Thermoplasma volcanium (Tv) was expressed
      in Escherichia coli, crystallized, and its X-ray molecular structure was
      determined in a complex with its substrate R5P and with substrate analogs
      beta,gamma-methylene ATP and ADP in two monoclinic crystal forms, P2(1). The
      beta,gamma-methylene ATP- and the ADP-bound binary structures were determined
      from crystals grown from ammonium sulfate solutions; these crystals diffracted to
      1.8 A and 1.5 A resolutions, respectively. Crystals of the ternary complex with
      ADP-Mg(2+) and R5P were grown from a polyethylene glycol solution in the absence
      of sulfate ions, and they diffracted to 1.8 A resolution; the unit cell is
      approximately double the size of the unit cell of the crystals grown in the
      presence of sulfate. The Tv PRPP synthetase adopts two conformations, open and
      closed, at different stages in the catalytic cycle. The binding of substrates,
      R5P and ATP, occurs with PRPP synthetase in the open conformation, whereas
      catalysis presumably takes place with PRPP synthetase in the closed conformation.
      The Tv PRPP synthetase forms a biological dimer in contrast to the tetrameric or
      hexameric quaternary structures of the Methanocaldococcus jannaschii and Bacillus
      subtilis PRPP synthetases, respectively.

PMID- 21963989
TI  - DARPins recognizing the tumor-associated antigen EpCAM selected by phage and
      ribosome display and engineered for multivalency.
AB  - Designed Ankyrin Repeat Proteins (DARPins) represent a novel class of binding
      molecules. Their favorable biophysical properties such as high affinity,
      stability and expression yields make them ideal candidates for tumor targeting.
      Here, we describe the selection of DARPins specific for the tumor-associated
      antigen epithelial cell adhesion molecule (EpCAM), an approved therapeutic target
      on solid tumors. We selected DARPins from combinatorial libraries by both phage
      display and ribosome display and compared their binding on tumor cells. By
      further rounds of random mutagenesis and ribosome display selection, binders with
      picomolar affinity were obtained that were entirely monomeric and could be
      expressed at high yields in the cytoplasm of Escherichia coli. One of the
      binders, denoted Ec1, bound to EpCAM with picomolar affinity (K(d)=68 pM), and
      another selected DARPin (Ac2) recognized a different epitope on EpCAM. Through
      the use of a variety of bivalent and tetravalent arrangements with these DARPins,
      the off-rate on cells was further improved by up to 47-fold. All EpCAM-specific
      DARPins were efficiently internalized by receptor-mediated endocytosis, which is
      essential for intracellular delivery of anticancer agents to tumor cells. Thus,
      using EpCAM as a target, we provide evidence that DARPins can be conveniently
      selected and rationally engineered to high-affinity binders of various formats
      for tumor targeting.

PMID- 21963991
TI  - Glyceraldehyde-3-phosphate dehydrogenase as a quinone reductase in the
      suppression of 1,2-naphthoquinone protein adduct formation.
AB  - 1,2-Naphthoquinone (1,2-NQ) is electrophilic, and forms covalent bonds with
      protein thiols, but its two-electron reduction product 1,2-dihydroxynaphthalene
      (1,2-NQH(2)) is not, so enzymes catalyzing the reduction with reduced pyridine
      nucleotides as cofactors could protect cells from electrophile-based chemical
      insults. To assess this possibility, we examined proteins isolated from the 9000g
      supernatant from mouse liver for 1,2-NQ reductase activity using an HPLC assay
      procedure for the hydroquinone of 1,2-NQ and Cibacron Blue 3GA column
      chromatography and Western blot analysis with specific antibody to determine 1,2
      NQ-bound proteins. Among the proteins with high affinities for pyridine
      nucleotides that also inhibited 1,2-NQ-protein adduct formation in the presence
      of NADH, a 37-kDa protein was found and identified as glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH). Using recombinant human GAPDH, we found that this
      glycolytic enzyme indeed catalyzes the two-electron reduction of 1,2-NQ
      accompanied by extensive NADH consumption under 20% oxygen conditions. When
      either 1,2-NQH(2) or 1,2-NQ was incubated with GAPDH in the presence of NADH,
      minimal covalent bonding to the enzyme occurred compared to that in its absence.
      These results indicate that GAPDH can inhibit 1,2-NQ-based electrophilic protein
      modification by conversion to the nonelectrophilic 1,2-NQH(2) via an NADH
      dependent process.

PMID- 21963992
TI  - Therapeutic hypothermia in the management of acute liver failure.
AB  - A large body of experimental data and preliminary clinical studies point to the
      induction of mild hypothermia (32-35  degrees C) as a valuable approach to
      control the development of brain edema and intracranial hypertension in acute
      liver failure (ALF). The ability of hypothermia to affect multiple processes
      probably explains its efficacy to prevent these cerebral complications.
      Remarkably, mild hypothermia has been shown to prevent or attenuate most of the
      major alterations involved in the pathogenesis of the cerebral complications of
      ALF, including the accumulation of ammonia in the brain and the circulation, the
      alterations of brain glucose metabolism, the brain osmotic disturbances, the
      accumulation of glutamate and lactate in brain extracellular space, the
      development of inflammation and oxidative/nitrosative stress, and others. Limited
      information suggests that the systemic effects of hypothermia may also be
      beneficial for some peripheral complications of ALF. Translation of the
      beneficial effects of therapeutic hypothermia into standard clinical practice,
      however, needs to be confirmed in adequately designed clinical trials. Such
      trials will be important to determine the safety of therapeutic hypothermia, to
      identify which patients might benefit from it, and to provide the optimal
      guidelines for its use in patients with ALF.

PMID- 21963990
TI  - Reactive oxygen species alter autocrine and paracrine signaling.
AB  - Cytochrome P450 (P450) 3A4 (CYP3A4) is the most abundant P450 protein in human
      liver and intestine and is highly inducible by a variety of drugs and other
      compounds. The P450 catalytic cycle is known to uncouple and release reactive
      oxygen species (ROS), but the effects of ROS from P450 and other enzymes in the
      endoplasmic reticulum have been poorly studied from the perspective of effects on
      cell biology. In this study, we expressed low levels of CYP3A4 in HepG2 cells, a
      human hepatocarcinoma cell line, and examined effects on intracellular levels of
      ROS and on the secretion of a variety of growth factors that are important in
      extracellular communication. Using the redox-sensitive dye RedoxSensor red, we
      demonstrate that CYP3A4 expression increases levels of ROS in viable cells. A
      custom ELISA microarray platform was employed to demonstrate that expression of
      CYP3A4 increased secretion of amphiregulin, intracellular adhesion molecule 1,
      matrix metalloprotease 2, platelet-derived growth factor (PDGF), and vascular
      endothelial growth factor, but suppressed secretion of CD14. The antioxidant N
      acetylcysteine suppressed all P450-dependent changes in protein secretion except
      for CD14. Quantitative RT-PCR demonstrated that changes in protein secretion were
      consistently associated with corresponding changes in gene expression. Inhibition
      of the NF-kappaB pathway blocked P450 effects on PDGF secretion. CYP3A4
      expression also altered protein secretion in human mammary epithelial cells and
      C10 mouse lung cells. Overall, these results suggest that increased ROS
      production in the endoplasmic reticulum alters the secretion of proteins that
      have key roles in paracrine and autocrine signaling.

PMID- 21963993
TI  - Hepatitis B and C virus prevalence and related factors in patients with
      inflammatory bowel diseases.

PMID- 21963994
TI  - Analysis of the association between transcription factor binding site variants
      and distinct accompanying regulatory motifs in yeast.
AB  - It is generally accepted that genes are regulated by the interactions between
      transcription factors (TFs) and their binding sites (TFBSs). Some studies have
      demonstrated that nucleotide variants at variable positions in TFBSs affect yeast
      gene regulation. Furthermore, variable positions in TFBSs in association with
      distinct accompanying regulatory motifs of other TFs (i.e., co-TFs) can also
      impact gene regulation in eukaryotes. Given that, even low-affinity TF-DNA
      interactions are abundant in vivo; we used both low- and high-affinity TFBSs and
      performed a genome-wide analysis of associations between variable positions and
      co-TFs. We found that, in Saccharomyces cerevisiae, approximately 14% of the
      variable positions in TFBSs demonstrate such associations. These associations
      occurred in close proximity on the same promoters (i.e., highly co-localized).
      Moreover, such associations were highly conserved between sensu stricto yeasts
      and also influenced gene expression, which were consistent with enriched
      functional categories.

PMID- 21963995
TI  - In silico and in vivo identification of the intermediate filament vimentin that
      is downregulated downstream of Brachyury during Xenopus embryogenesis.
AB  - Brachyury, a member of the T-box transcription family, has been suggested to be
      essential for morphogenetic movements in various processes of animal development.
      However, little is known about its critical transcriptional targets. In order to
      identify targets of Brachyury and understand the molecular mechanisms underlying
      morphogenetic movements, we first searched the genome sequence of Xenopus
      tropicalis, the only amphibian genomic sequence available, for Brachyury-binding
      sequences known as T-half sites, and then screened for the ones conserved between
      vertebrate genomes. We found three genes that have evolutionarily conserved T
      half sites in the promoter regions and examined these genes experimentally to
      determine whether their expressions were regulated by Brachyury, using the animal
      cap system of Xenopus laevis embryos. Eventually, we obtained evidence that
      vimentin, encoding an intermediate filament protein, was a potential target of
      Brachyury. This is the first report to demonstrate that Brachyury might affect
      the cytoskeletal structure through regulating the expression of an intermediate
      filament protein, vimentin.

PMID- 21963996
TI  - Effect of probiotic fermented milk and chlorophyllin on gene expressions and
      genotoxicity during AFB1-induced hepatocellular carcinoma.
AB  - The aim of this study was to investigate the chemopreventive effect of probiotic
      fermented milk and chlorophyllin on aflatoxin B1 (AFB1) induced hepatocellular
      carcinoma. In vivo trials were conducted on 200 Wistar rats allocated to eight
      groups. Rats in the positive control group were given intraperitoneal injection
      of aflatoxin B1 at 450 MUg/kg body weight twice a week for 6 weeks. The rats were
      sacrificed and dissected at 25th week of the experiment, and comet assay was
      carried out in hepatic cells to assess the genotoxicity or DNA damage. The tumour
      incidence was decreased by approximately one-third than AFB1 control group. The
      expression of c-myc bax, bcl-2, cyclin D1, p53 and rasp-21 genes was also
      studied. A significant (P<0.05) reduction in DNA damage was observed in probiotic
      fermented milk with chlorophyllin group as compared to aflatoxin B1 control
      group. The c-myc, bcl-2, cyclin D1 and rasp-21 level was found to be highest in
      AFB1 control group as compared to the treatment group. The results advocate the
      enhanced protective potential of probiotic fermented milk and chlorophyllin
      against AFB1-induced molecular alterations in hepatic cells during
      carcinogenesis.

PMID- 21963997
TI  - YC-1 attenuates hypoxia-induced pulmonary arterial hypertension in mice.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is characterized by a
      progressive increase in pulmonary vascular resistance and elevation of pulmonary
      arterial pressure, leading to right ventricular failure and eventual death.
      Currently, no curative therapy for PAH is available, and the overall prognosis is
      very poor. Recently, direct activators of soluble guanylyl cyclase (sGC) have
      been tested as a novel therapeutic modality in experimental models of pulmonary
      arterial hypertension (PAH). OBJECTIVE: In this study, we used in vitro and in
      vivo models to evaluate the therapeutic potential of 3-(5'-hydroxymethyl-2'
      furyl)-1-benzylindazole (YC-1), a dual functioning chemical, as a direct
      activator of guanylyl cyclase and an inhibitor of hypoxia-inducible factor-1.
      METHODS: We analyzed the effects of YC-1 on cell proliferation and the levels of
      p21 and p53 in human pulmonary artery smooth muscle cells (HPASMCs) under
      hypoxia. We also determined the effects of YC-1 on expression of endothelin-1 (ET
      1) and phosphorylation status of endothelial nitric oxide synthase (eNOS) at
      Ser(1179) in human pulmonary artery endothelial cells (HPAECs) under hypoxia. In
      mice, hypoxic PAH was induced by exposure to normobaric hypoxic conditions for 28
      days. To assess preventive or therapeutic effects, randomized mice were subjected
      to once daily i.p. injections of YC-1 for the entire hypoxic period (5 mg/kg) or
      for the last seven days of a 28-day hypoxic period (5 and 10 mg/kg). On day 28,
      we measured the right ventricular systolic pressure (RVSP) and determined the
      degrees of right ventricular hypertrophy (RVH) and vascular remodeling. RESULTS:
      In HPASMCs, YC-1 inhibited hypoxia-induced proliferation and induction of p53 and
      p21 in a concentration-dependent manner. Also, YC-1 suppressed the hypoxia
      induced expression of ET-1 mRNA and dephosphorylation of eNOS at Ser(1179) in
      HPAECs. In the preventive in vivo model, a daily dose of 5 mg/kg YC-1
      significantly prevented the elevation of RVSP, development of RVH, and pulmonary
      vascular remodeling, which were caused by hypoxic exposure. In the therapeutic
      model, YC-1 at daily doses of 5 and 10 mg/kg alleviated RVH and pulmonary
      vascular remodeling but did not prevent the elevation of RVSP. CONCLUSIONS: Our
      results indicate that YC-1 prevents the development of hypoxia-induced PAH in a
      preventive model and alleviates RVH and pulmonary vascular remodeling in a
      therapeutic model. Therefore, these data imply that YC-1 has therapeutic
      potential for use in a single or combination therapy for PAH.

PMID- 21963998
TI  - Novel paramagnetic AT1 receptor antagonists.
AB  - Novel paramagnetic selective angiotensin AT(1) receptor antagonists (sartans)
      bearing nitroxides (3, 4) have been prepared and their pharmacology evaluated in
      vitro as well as in vivo. Compounds 3, 4 proved to be effective sartans with
      pK(B) estimates in the range 6.2-9.1. In addition, the sodium salt (11) of 4 (R =
      Bu) is able to protect against vascular injury in hypertensive rats as determined
      by its ability to attenuate the development of intimal thickening caused by
      balloon injury of the carotid artery.

PMID- 21963999
TI  - The European Medicines Agency review of Tegafur/Gimeracil/Oteracil (TeysunoTM)
      for the treatment of advanced gastric cancer when given in combination with
      cisplatin: summary of the Scientific Assessment of the Committee for medicinal
      products for human use (CHMP).
AB  - The product TeysunoTM (S-1) contains tegafur, a prodrug of 5-fluorouracil (5-FU),
      and two modulators of 5-FU metabolism, gimeracil and oteracil. The main clinical
      study in this application was a randomized controlled study comparing S-1 plus
      cisplatin with 5-FU plus cisplatin. In this study, median overall survival times
      of 8.6 months and 7.9 months for S-1 plus cisplatin and 5-FU plus cisplatin,
      respectively, were observed (hazard ratio, 0.92; 95% confidence interval, 0.80
      1.05). The Committee for Medicinal Products for Human Use of the European
      Medicines Agency concluded that S-1 in combination with cisplatin (75 mg/m2) was
      noninferior to 5-FU plus cisplatin (100 mg/m2) in patients with advanced gastric
      cancer and adopted a positive opinion recommending the marketing authorization
      for this product for the treatment of advanced gastric cancer when given in
      combination with cisplatin. The recommended dose of S-1 is 25 mg/m2 (expressed as
      tegafur content) twice a day, for 21 consecutive days followed by 7 days rest
      (one treatment cycle), in combination with 75 mg/m2 cisplatin i.v. administered
      on day 1. This treatment cycle is repeated every 4 weeks. The most common side
      effects reported in the pivotal study were anemia, neutropenia, vomiting,
      diarrhea, abdominal pain, weight decrease, anorexia, and fatigue. The objective
      of this paper is to summarize the scientific review of the application leading to
      approval in the EU. The full scientific assessment report and the summary of
      product characteristics are available on the European Medicines Agency website
      (http://www.ema.europa.eu).

PMID- 21964000
TI  - The significance of hurthle cells in thyroid disease.
AB  - Hurthle cells (HCs) and HC change, along with the frequently employed synonyms
      "oncocytes/oncocytic change" or "oxyphils/oxyphilic change," are not infrequently
      described on fine-needle aspiration biopsy (FNAB) reports of thyroid lesions. The
      description of HCs on FNAB reports may cause significant concern to the
      clinician; however, placing the finding in the appropriate clinical context may
      alleviate some anxiety. Not all oxyphilic cells are true HCs and not every
      aspirate containing HCs is or should be considered equivalent to an HC neoplasm
      (HCN). There are many benign thyroid lesions associated with HCs or HC change.
      For clinicians, it may be difficult to discern the significance of these findings
      and to determine an appropriate course of action. A skilled and experienced
      cytopathologist is invaluable in discriminating the subtle features that
      distinguish these lesions from those warranting a more aggressive approach. The
      diagnosis of HC carcinoma relies on histopathologic scrutiny and evidence of
      capsular and/or vascular invasion or metastasis to lymph nodes or distant organs.
      Many investigators have sought clinical, radiographic, cytological, genetic, and
      other factors to attempt to discriminate preoperatively between benign and
      malignant HCNs. To date, none have been definitively proven to be reliable. For
      now, because of the inability to determine the benign or malignant nature of such
      neoplasms based on cytology alone, a surgical approach is warranted.

PMID- 21964001
TI  - Preliminary report: vitamin D deficiency in advanced cancer patients with
      symptoms of fatigue or anorexia.
AB  - BACKGROUND: Vitamin D deficiency in noncancer patients is associated with
      symptoms of fatigue, muscle weakness, and depression. These symptoms are common
      among advanced cancer patients. We investigated the prevalence of low serum
      vitamin D levels in cancer patients with fatigue or poor appetite and their
      association with symptom burden and other correctable endocrine abnormalities.
      METHODS: This was a retrospective review of 100 consecutive cancer patients with
      appetite or fatigue scores of >=4 of 10 referred to a supportive care clinic. We
      investigated serum levels of 25(OH) vitamin D, cortisol, thyroid-stimulating
      hormone, and bioavailable testosterone. Symptoms were measured by the Edmonton
      Symptom Assessment Scale. Serum 25(OH) vitamin D <20 ng/mL was considered
      deficient; >=20 ng/mL and <30 ng/mL were considered insufficient. RESULTS:
      Patients were predominantly male (68%) and white (66%), with a median age of 60
      years (range, 27-91 years). Gastrointestinal (30%) and lung (22%) cancers were
      predominant. Forty-seven patients (47%) were vitamin D deficient and 70 (70%)
      were insufficient. Thirteen of 70 patients (19%) with vitamin D insufficiency
      were on supplementation. Vitamin D deficiency was more common among nonwhites
      (82% versus 36%) and females. No significant association was found between
      vitamin D and symptoms. Hypogonadic males had a significantly lower mean 25(OH)
      vitamin D level than eugonadic males. CONCLUSIONS: Low vitamin D levels were
      highly prevalent among advanced cancer patients with cachexia or fatigue. Vitamin
      D deficiency was more frequent among nonwhite and female patients. Vitamin D
      levels were also significantly lower in male patients with hypogonadism.

PMID- 21964002
TI  - HFS-14, a specific quality of life scale developed for patients suffering from
      hand-foot syndrome.
AB  - BACKGROUND: Hand-foot syndrome (HFS) is a common reaction to certain
      chemotherapies and new targeted therapies, impairing patient quality of life
      (QoL). However, there is currently no specific tool to measure QoL in patients
      with HFS. Objective. The objective was to develop and validate a HFS-specific QoL
      questionnaire (HFS-14). PATIENTS AND METHODS: From a list of 31 items identified
      from a literature review and patient interview notes, item reduction and pilot
      testing by cognitive debriefing resulted in a final 14-item questionnaire with
      excellent internal reliability. Clinical validity was assessed in 43 patients
      with HFS by comparing the HFS-14 score according to HFS clinical grade based on
      the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI
      CTCAE), version 3.0, and by measuring its correlation with the Dermatology Life
      Quality Index (DLQI), Skindex-16, and short-form 12 health-related questionnaires
      and pain measurement. RESULTS: The mean HFS-14 score was significantly higher in
      patients with clinical grade 2 and grade 3 HFS than in those with grade 1 HFS.
      The higher the HFS-14 score, the greater the QoL impairment. The HFS-14 score was
      highly correlated with the DLQI and Skindex-16 scores. In the population of
      patients with severe grade 3 NCI-CTCAE HFS, the HFS-14 score was significantly
      higher in patients having both hands and feet severely involved than in those
      with severe involvement of one limb (hands or feet) with the other one less
      severely affected. CONCLUSIONS: This scale specifically developed for patients
      with HFS is a valid and valuable tool for measuring HFS-related QoL impairment.

PMID- 21964003
TI  - The epothilones: new therapeutic agents for castration-resistant prostate cancer.
AB  - The management of castration-resistant prostate cancer (CRPC) presents a clinical
      challenge because of limitations in efficacy and durability with currently
      available therapeutics. The epothilones represent a novel class of anticancer
      therapy that stabilizes microtubules, causing cell death and tumor regression in
      preclinical models. The structure of the tubulin-binding site for epothilones is
      distinct from that of the taxanes. Moreover, preclinical studies suggest
      nonoverlapping mechanisms of resistance between epothilones and taxanes. In early
      phase studies in patients with CRPC, treatment with ixabepilone, a semisynthetic
      analog of epothilone B, induced objective responses and prostate-specific antigen
      declines in men previously progressing on docetaxel-based regimens. Clinical
      activity has been observed in nonrandomized trials for patients with CRPC using
      ixabepilone in the first- and second-line settings as a single agent and in
      combination with estramustine. Patupilone and sagopilone were also shown to have
      promising efficacy in phase II clinical trials of patients with CRPC. All three
      epothilones appear to be well tolerated, with modest rates of neutropenia and
      peripheral neuropathy. The lack of crossresistance between epothilones and
      taxanes may allow sequencing of these agents. Evaluating epothilones in phase III
      comparative trials would provide much-needed insight into their potential place
      in the management of patients with CRPC.

PMID- 21964004
TI  - The evolution of the locoregional therapy of breast cancer.
AB  - Breast-conserving therapy (BCT) and mastectomy have equal survival outcomes.
      Rates of local recurrence after BCT have declined steadily, largely as a result
      of the widespread use of systemic therapy. Sentinel node biopsy has replaced
      axillary dissection for staging the axilla, and in women undergoing BCT with
      whole-breast irradiation (WBI), axillary dissection is not needed for local
      control or survival in those with fewer than three involved sentinel nodes.
      Alternatives to 6 weeks of WBI have been shown to be safe and effective for
      subsets of breast cancer patients, and the use of preoperative chemotherapy
      allows BCT in some women who require mastectomy if surgery is the initial step in
      treatment. The combination of the smaller cancers detected with screening and the
      routine use of multimodality therapy has resulted in a decrease in the morbidity
      of local therapy and improved cancer treatment outcomes.

PMID- 21964005
TI  - Disparities between blacks and whites in tobacco and lung cancer treatment.
AB  - Racial disparities exist in lung cancer incidence, morbidity, and mortality.
      Smoking is responsible for the majority of lung cancers, and racial disparities
      also exist in smoking outcomes. Black smokers are less likely than white smokers
      to engage in evidence-based tobacco treatment, and black smokers are less likely
      than white smokers to stop smoking. Continued smoking following a lung cancer
      diagnosis is a potential indicator of poor lung cancer treatment outcomes, yet
      lung cancer patients who smoke are unlikely to receive evidence-based tobacco
      treatment. The risks from continued smoking after diagnosis deserve attention as
      a modifiable factor toward lessening racial disparities in lung cancer outcomes.

PMID- 21964006
TI  - Non-adherence to medication and cardiovascular risk.

PMID- 21964007
TI  - Managing atrial fibrillation: the growing challenge.

PMID- 21964008
TI  - Rheumatic fever in New Zealand: from perennial failure to successful eradication.

PMID- 21964009
TI  - Under-use of secondary prevention medication in acute coronary syndrome patients
      treated with in-hospital coronary artery bypass graft surgery.
AB  - BACKGROUND: Acute coronary syndrome (ACS) patients treated with inpatient
      coronary artery bypass graft (CABG) surgery are at significant risk for future
      Major Adverse Cardiovascular events (MACE). The use of evidence-based medications
      (aspirin, statins, beta-blockers and angiotensin converting enzyme (ACE)
      inhibitors/angiotensin receptor blockers (ARBS)) can reduce MACE in these
      patients. METHODS: We used a prospective database of all patients admitted to the
      Green Lane Cardiovascular Service, Coronary Care Unit (CCU) at Auckland City
      Hospital (ACH). We contacted patients General Practitioners for current patient
      data including MACE, which was supplemented by using the hospital patient
      records. RESULTS: From 1/6/2006 to 31/7/2007, 901 patients presented with an ACS;
      of these 129 received inpatient CABG. 2 patients died before hospital discharge.
      At a median follow up time of 2.9 [IQR 2.7-3.3] years, 109 (86%) patients were
      traced and their medication assessed. Only 90 (83%) patients remained on aspirin,
      78 (72%) on statins, 67 (62%) on beta-blockers and 47 (43%) on ACE
      inhibitors/ARBs. From the total of 127 patients discharged from hospital, there
      were a total of 18 MACE (6.2%/year): 3 unstable angina, 4 non-ST elevation
      myocardial infarction (NSTEMI), 6 congestive heart failure (CHF) and 5 deaths.
      CONCLUSION: Suboptimal use of secondary prevention drugs in high risk ACS
      patients treated with urgent CABG surgery may contribute to subsequent adverse
      events. Greater efforts to optimise the use of these medications are needed to
      improve outcomes.

PMID- 21964010
TI  - The incidence of atrial fibrillation and the use of warfarin in Northland, New
      Zealand stroke patients.
AB  - AIM: To identify the number of Northland stroke patients with atrial fibrillation
      (AF) and to assess the effective use of warfarin anticoagulation in this group
      METHOD: A retrospective study of patients admitted with stroke or transient
      ischaemic attack (TIA) to Whangarei Hospital between 1 Jan 2010 and 1 Sept 2010.
      RESULTS: Of 198 stroke/TIA patients identified, 47 (24%) had confirmed persistent
      or paroxysmal AF (PAF) or flutter. Only 12 (31%) patients with pre existing PAF
      or AF were on warfarin and only 1 patient had an ischaemic stroke while in the
      therapeutic INR range of 2.0-3.0. The commonest reason cited for no
      anticoagulation was patients' wishes. CONCLUSION: In our region, effective
      warfarin use for stroke prevention in AF patients is lower than recommended. This
      may be improved with increased awareness of efficacy and safety of warfarin and
      more thorough monitoring of INR.

PMID- 21964011
TI  - Surgical radiofrequency ablation for atrial fibrillation: the Christchurch, New
      Zealand experience.
AB  - AIMS: To report the long-term results following surgical radiofrequency ablation
      (RFA) for atrial fibrillation as an adjunct to other cardiac surgery at
      Christchurch Hospital. METHODS: A retrospective observational audit review of
      outcomes. The sample population included all patients identified as having
      undergone surgical RFA for atrial fibrillation at Christchurch Hospital, between
      the first procedure performed on 2 July 2001 and 28 January 2009. RESULTS: A
      total of 44 patients underwent surgical RFA between 2 July 2001 and 28 January
      2009. Postoperatively there were three deaths prior to discharge (7%). Pacemakers
      were required in four patients (9%), and two patients subsequently underwent
      catheter ablation for atrial arrhythmias. In the immediate postoperative period
      only three patients remained in atrial fibrillation. At last follow-up up to 102
      months from surgery (45 plus or minus 29 months), 27 patients had developed
      persistent atrial fibrillation and four persistent atrial flutter. Persisting
      long-term benefit was seen in seven patients (18%, 7/38); five patients were in
      stable sinus rhythm, one had paroxysmal atrial fibrillation and one paroxysmal
      atrial flutter. CONCLUSIONS: Whilst the procedure was effectively acutely, the
      recurrence of atrial fibrillation was high and development of new atrial flutter
      common over long-term follow-up.

PMID- 21964012
TI  - Pulmonary vein ablation for atrial fibrillation: the Christchurch, New Zealand
      experience.
AB  - AIMS: To report the long-term results following percutaneous pulmonary vein
      ablation (PVA) for atrial fibrillation (AF) at Christchurch Hospital. METHODS: A
      retrospective observational audit review of outcomes. The sample population
      included all patients identified as having undergone percutaneous radiofrequency
      ablation of multiple pulmonary veins at Christchurch Hospital, from the first
      procedure performed on 29 September 2001 until 15 December 2009. RESULTS: A total
      of 187 patients underwent pulmonary vein ablation. The patient population was
      predominantly younger (mean age 51) and male (83%) with no important comorbidity.
      Following a single procedure only, the chance of remaining free of AF at 12
      months was 0.74 for patients with paroxysmal AF (PAF) and 0.60 for patients with
      persistent AF (PsAF). 52 patients (28%) underwent a repeat procedure within 12
      months of their index ablation owing to early recurrence of AF. 5-year survival
      free of clinical AF when analysed following these early repeat procedures, if
      required, was 0.74 and 0.56 for PAF and PsAF patients respectively. Complications
      occurred following 6% of procedures and were serious in 2.5%. New atrial flutter
      developed in 6% of patients. CONCLUSIONS: PVA is an effective treatment for AF,
      with better outcomes in patients with paroxysmal atrial fibrillation. However, as
      it carries a significant risk, we recommend that its application be reserved for
      patients with highly symptomatic, medication-refractory disease.

PMID- 21964013
TI  - Prediction of cardiac rhythm 1 year following cardioversion for atrial
      fibrillation.
AB  - BACKGROUND: There is little recent information regarding outcome and its
      determinants following cardioversion (CV) for atrial fibrillation (AF) or
      flutter. This study aims to help improve prediction of cardiac rhythm outcome
      following CV for AF. METHODS: Cardiac rhythm at 6 weeks and 12 months was
      documented following elective (EC; n=496) or immediate (IC; n=52) cardioversion
      for AF or atrial flutter in a single referral centre. RESULTS: 65 and 58% of IC
      patients remained in sinus rhythm (SR) 6 weeks and 1 year after CV (respectively)
      compared with 43% and 30% in EC patients (P<0.001). Independent positive
      predictors of SR 6 weeks after cardioversion included amiodarone therapy (OR 2.04
      [1.28-3.33], P<0.01) and atrial flutter (OR 1.85 [1.09-3.13], P<0.05). Negative
      predictors included the need for >1 shock to achieve SR (OR 1.61 [1.12-2.37],
      P=0.011) and arrhythmia duration, (OR 0.96 [0.95-0.97], P<0.001). At 1 year,
      amiodarone, duration of arrhythmia and the need for >1 shock remained independent
      predictors of rhythm. CONCLUSIONS: The number of shocks required to achieve SR is
      a newly demonstrated independent predictor of rhythm outcome after elective CV.

PMID- 21964014
TI  - Early cardiac morbidity of rheumatic fever in children in New Zealand.
AB  - AIM: The aim of this study was to review the severity and morbidity of acute
      rheumatic fever (ARF) and rheumatic heart disease (RHD) for children with the
      most significant cardiac disease in the current era in New Zealand. METHOD:
      Retrospective 2-year review of children with ARF and RHD admitted to Starship
      Children's cardiology ward. Medical and surgical admissions were classified.
      Echocardiographic severity of cardiac disease and cardiac surgical data were
      analyzed. Using length of stay data and 2009 District Health Board costings,
      admission costs were calculated. RESULTS: 36 children had 49 admissions. Mean age
      11.8 plus or minus 2.4 years. All but one child was of Maori or Pacific Island
      ethnicity. 10 children had symptoms and signs of congestive cardiac failure on
      admission. The average length of stay was 23 days, but the subset of children
      with ARF requiring cardiac surgery at the same admission had an average of 54
      days (range 36-78 days) in hospital. The total hospital costs over the 2-year
      period was $1,918,600. CONCLUSION: Failure to prevent rheumatic fever in New
      Zealand means that there is significant cardiac sequelae for those children who
      develop severe RHD. The early morbidity includes heart failure, need for cardiac
      surgery, and prolonged hospital stay.

PMID- 21964015
TI  - Are we meeting cardiovascular risk targets 3 years after acute coronary syndrome?
      An evaluation in West Auckland, New Zealand.
AB  - AIM: Several studies have shown poor achievement of cardiovascular targets in
      high risk patients. We measured these targets in patients with Acute Coronary
      Syndrome, three years after discharge from Waitakere Coronary Care Unit. METHOD:
      A retrospective observational study was performed. All patients discharged in
      2006 were included. Admission data was extracted from computerised records and
      patients were subsequently invited for appointment. Data collected included:
      blood pressure, lipid profile, BMI, smoking status, HbA1c, medications and
      contraindications, and lifestyle factors. Results were analysed and compared with
      national targets. RESULTS: Data was collected on 112 patients (22 patients died,
      18 excluded and 18 lost to follow up). There was good compliance with blood
      pressure (mean 120/70 mmHg), smoking cessation and medication targets. However
      22% of patients were not prescribed an ACE inhibitor at follow-up. Lipid profile
      improved, although only 52% of patients met LDL targets. There was no difference
      between admission and follow-up BMI. HbA1c had increased slightly, however this
      was not statistically significant. Eight diabetic patients (n=27) had an HbA1c of
      less than 7% at follow-up. CONCLUSION: Although a small sample population,
      results showed mixed compliance but not as poor as previously reported. More
      effort is needed to attain LDL, HbA1c and BMI targets, and ensure ACE inhibitor
      initiation.

PMID- 21964016
TI  - Anti-tumour-necrosis-factor-alpha agents and the heart: beyond left ventricular
      systolic dysfunction?

PMID- 21964017
TI  - How safe is the 'safe triangle'?

PMID- 21964018
TI  - Medical image. Post mortem diagnosis of severe sepsis.

PMID- 21964019
TI  - Pre-hospital antibiotics for meningococcal disease remains low.

PMID- 21964020
TI  - Response to letter 'New Zealand's shocking diabetes rates can be reduced--9
      urgently needed actions'.

PMID- 21964021
TI  - Portrayal of tobacco in televised music videos: content analysis and trends.

PMID- 21964022
TI  - Response to review article by Ernst and Posadzki on spinal manipulation.

PMID- 21964023
TI  - Is colorectal cancer preventable?

PMID- 21964024
TI  - MHC class I family proteins retard systemic lupus erythematosus autoimmunity and
      B cell lymphomagenesis.
AB  - Dysregulation of the T cell-dependent Ab response can lead to numerous
      immunological disorders, ranging from systemic lupus erythematosus to B cell
      lymphomas. Cellular processes governed by MHC class II proteins play a major role
      in this response and its dysregulation. The extent to which processes controlled
      by the diverse family of MHC class I proteins impact such autoimmune and
      neoplastic disorders, however, is less clear. In this study, we genetically
      dissect the contributions of individual MHC class I family members and the
      pathological processes under their control in the systemic lupus erythematosus
      like disease of BXSB.Yaa mice and B cell lymphomagenesis of SJL mice. This study
      reveals a powerful repressive regulatory axis comprised of MHC class I-dependent
      CD8(+) T cells and NK cells. These results indicate that the predominant role of
      the MHC class I protein family in such immunological disorders is to protect from
      more aggressive diseases.

PMID- 21964025
TI  - IL-17 boosts proinflammatory outcome of antiviral response in human cells.
AB  - Excessive inflammation during bacterial and viral infections is destructive to
      the host and involves elevated production of proinflammatory cytokines. It is
      especially deleterious in organs with space constraints such as lung and the CNS.
      Indeed, a number of viruses that infect lungs, such as avian influenza virus,
      SARS-associated coronavirus, and respiratory syncytial virus, elicit a very high
      level of proinflammatory cytokines; however, it is unclear what triggers their
      production. In this study, we show that IL-17 commonly produced during viral
      infection specifically augments a proinflammatory response by directly
      synergizing with antiviral signaling. Costimulation of primary human fibroblasts
      with IL-17 greatly enhanced respiratory syncytial virus-induced or synthetic
      dsRNA-based viral mimic polyinosinic:polycytidylic acid-induced expression of
      proinflammatory genes without affecting expression of IFN-beta-stimulated or IFN
      stimulated genes. Knockdown of expression of known mediators of the antiviral
      signaling pathway revealed that the IL-17-poly(I:C) synergy depends on the
      presence of the transcriptional factors RelA and IFN regulatory factor 3 and
      IkappaB kinases. Moreover, this synergy was blocked by an IkappaB kinase
      inhibitor, BAY 11-7082. These findings shed light on the molecular mechanisms
      behind IL-17-dependent immunopathology observed in viral infections.

PMID- 21964026
TI  - Protein kinase Cepsilon regulates proliferation and cell sensitivity to TGF-1beta
      of CD4+ T lymphocytes: implications for Hashimoto thyroiditis.
AB  - We have studied the functional role of protein kinase Cepsilon (PKCepsilon) in
      the control of human CD4(+) T cell proliferation and in their response to TGF
      1beta. We demonstrate that PKCepsilon sustains CD4(+) T cell proliferation
      triggered in vitro by CD3 stimulation. Transient knockdown of PKCepsilon
      expression decreases IL-2R chain transcription, and consequently cell surface
      expression levels of CD25. PKCepsilon silencing in CD4 T cells potentiates the
      inhibitory effects of TGF-1beta, whereas in contrast, the forced expression of
      PKCepsilon virtually abrogates the inhibitory effects of TGF-1beta. Being that
      PKCepsilon is therefore implicated in the response of CD4 T cells to both CD3
      mediated proliferative stimuli and TGF-1beta antiproliferative signals, we
      studied it in Hashimoto thyroiditis (HT), a pathology characterized by abnormal
      lymphocyte proliferation and activation. When we analyzed CD4 T cells from HT
      patients, we found a significant increase of PKCepsilon expression, accounting
      for their enhanced survival, proliferation, and decreased sensitivity to TGF
      1beta. The increased expression of PKCepsilon in CD4(+) T cells of HT patients,
      which is described for the first time, to our knowledge, in this article, viewed
      in the perspective of the physiological role of PKCepsilon in normal Th
      lymphocytes, adds knowledge to the molecular pathophysiology of HT and creates
      potentially new pharmacological targets for the therapy of this disease.

PMID- 21964027
TI  - Granule-derived granzyme B mediates the vulnerability of human neurons to T cell
      induced neurotoxicity.
AB  - Multiple sclerosis (MS) is considered an autoimmune disease of the CNS and is
      characterized by inflammatory cells infiltrating the CNS and inducing
      demyelination, axonal loss, and neuronal death. Recent evidence strongly suggests
      that axonal and neuronal degeneration underlie the progression of permanent
      disability in MS. In this study, we report that human neurons are selectively
      susceptible to the serine-protease granzyme B (GrB) isolated from cytotoxic T
      cell granules. In vitro, purified human GrB induced neuronal death to the same
      extent as the whole activated T cell population. On the contrary, activated T
      cells isolated from GrB knockout mice failed to induce neuronal injury. We found
      that following internalization through various parts of neurons, GrB accumulated
      in the neuronal soma. Within the cell body, GrB diffused out of endosomes
      possibly through a perforin-independent mechanism and induced subsequent
      activation of caspases and cleavage of alpha-tubulin. Inhibition of caspase-3, a
      well-known substrate for GrB, significantly reduced GrB-mediated neurotoxicity.
      We demonstrated that treatment of neurons with mannose-6-phosphate prevented GrB
      entry and inhibited GrB-mediated neuronal death, suggesting mannose-6-phosphate
      receptor-dependent endocytosis. Together, our data unveil a novel mechanism by
      which GrB induces selective neuronal injury and suggest potential new targets for
      the treatment of inflammatory-mediated neurodegeneration in diseases such as MS.

PMID- 21964028
TI  - Ornithodoros moubata complement inhibitor is an equally effective C5 inhibitor in
      pigs and humans.
AB  - Experimental evidence suggests that C inhibition and more particularly combined
      inhibition of C and the TLR coreceptor CD14 may be of therapeutic benefit in
      sepsis and other inflammatory conditions. A barrier to the testing and further
      development of many inhibitors is that their activity is species specific. Pig is
      a relevant species for experimental models of human disease, and this study
      undertakes a comprehensive comparison of the inhibitory efficacy of the C5
      inhibitor Ornithodoros moubata C inhibitor (OmCI) in human and porcine whole
      blood ex vivo models of Escherichia coli-induced sepsis. The effect of OmCI on
      complement activity in pigs undergoing E. coli sepsis was also examined. Porcine
      and human serum, and whole blood anticoagulated with lepirudin, was incubated
      with E. coli and the effect of OmCI investigated. The ex vivo results were
      virtually identical in pig and human. OmCI completely ablated the activity of all
      three C pathways at 0.64 MUM. E. coli-induced C activation and expression of
      CD11b (wCD11R3 in the pig), was abolished ex vivo at 0.32 MUM OmCI. Combining
      anti-CD14 and OmCI reduced the formation of IL-8 and TNF-alpha more potently than
      the single inhibitors. OmCI also efficiently bound E. coli-induced leukotriene
      B(4) in pig and human plasma. In support of our ex vivo findings, in vivo the
      activity of all C pathways was inhibited at 0.6 mg OmCI/kg pig. In conclusion,
      OmCI efficiently inhibited pig and human C activation, has accompanying anti
      inflammatory effects and is a promising candidate inhibitor for further in vivo
      studies of sepsis.

PMID- 21964029
TI  - NKT TCR recognition of CD1d-alpha-C-galactosylceramide.
AB  - NKT cells respond to a variety of CD1d-restricted glycolipid Ags that are
      structurally related to the prototypic Ag alpha-galactosylceramide (alpha
      GalCer). A modified analog of alpha-GalCer with a carbon-based glycosidic linkage
      (alpha-C-GalCer) has generated great interest because of its apparent ability to
      promote prolonged, Th1-biased immune responses. In this study, we report the
      activation of spleen NKT cells to alpha-C-GalCer, and related C-glycoside
      ligands, is weaker than that of alpha-GalCer. Furthermore, the Vbeta8.2 and
      Vbeta7 NKT TCR affinity for CD1d-alpha-C-GalCer, and some related analogs, is ~10
      fold lower than that for the NKT TCR-CD1d-alpha-GalCer interaction. Nevertheless,
      the crystal structure of the Vbeta8.2 NKT TCR-CD1d-alpha-C-GalCer complex is
      similar to that of the corresponding NKT TCR-CD1d-alpha-GalCer complex, although
      subtle differences at the interface provide a basis for understanding the lower
      affinity of the NKT TCR-CD1d-alpha-C-GalCer interaction. Our findings support the
      concept that for CD1d-restricted NKT cells, altered glycolipid ligands can
      promote markedly different responses while adopting similar TCR-docking
      topologies.

PMID- 21964030
TI  - Neuroinflammation and endoplasmic reticulum stress are coregulated by crocin to
      prevent demyelination and neurodegeneration.
AB  - Endoplasmic reticulum (ER) stress is a homeostatic mechanism, which is used by
      cells to adapt to intercellular and intracellular changes. Moreover, ER stress is
      closely linked to inflammatory pathways. We hypothesized that ER stress is an
      integral component of neuroinflammation and contributes to the development of
      neurological diseases. In autopsied brain specimens from multiple sclerosis (MS)
      and non-MS patients, XBP-1 spliced variant (XBP-1/s) was increased in MS brains
      (p < 0.05) and was correlated with the expression of the human endogenous
      retrovirus-W envelope transcript, which encodes the glycoprotein, Syncytin-1 (p <
      0.05). In primary human fetal astrocytes transfected with a Syncytin-1-expressing
      plasmid, XBP-1/s, BiP, and NOS2 were induced, which was suppressed by crocin
      treatment (p < 0.05). Crocin also protected oligodendrocytes exposed to cytotoxic
      supernatants derived from Syncytin-1-expressing astrocytes (p < 0.05) and NO
      mediated oligodendrocytotoxicity (p < 0.05). During experimental autoimmune
      encephalomyelitis (EAE), the transcript levels of the ER stress genes XBP-1/s,
      BiP, PERK, and CHOP were increased in diseased spinal cords compared with healthy
      littermates (p < 0.05), although CHOP expression was not involved in the EAE
      disease phenotype. Daily treatment with crocin starting on day 7 post-EAE
      induction suppressed ER stress and inflammatory gene expression in spinal cords
      (p < 0.05), which was accompanied by preserved myelination and axonal density,
      together with reduced T cell infiltration and macrophage activation. EAE
      associated neurobehavioral deficits were also ameliorated by crocin treatment (p
      < 0.05). These findings underscored the convergent roles of pathogenic ER stress
      and immune pathways in neuroinflammatory disease and point to potential
      therapeutic applications for crocin.

PMID- 21964031
TI  - Heligmosomoides polygyrus elicits a dominant nonprotective antibody response
      directed against restricted glycan and peptide epitopes.
AB  - Heligmosomoides polygyrus is a widely used gastrointestinal helminth model of
      long-term chronic infection in mice, which has not been well-characterized at the
      antigenic level. We now identify the major targets of the murine primary Ab
      response as a subset of the secreted products in H. polygyrus excretory-secretory
      (HES) Ag. An immunodominant epitope is an O-linked glycan (named glycan A)
      carried on three highly expressed HES glycoproteins (venom allergen Ancylostoma
      secreted protein-like [VAL]-1, -2, and -5), which stimulates only IgM Abs, is
      exposed on the adult worm surface, and is poorly represented in somatic parasite
      extracts. A second carbohydrate epitope (glycan B), present on both a non-protein
      high molecular mass component and a 65-kDa molecule, is widely distributed in
      adult somatic tissues. Whereas the high molecular mass component and 65-kDa
      molecules bear phosphorylcholine, the glycan B epitope itself is not
      phosphorylcholine. Class-switched IgG1 Abs are found to glycan B, but the
      dominant primary IgG1 response is to the polypeptides of VAL proteins, including
      also VAL-3 and VAL-4. Secondary Ab responses include the same specificities while
      also recognizing VAL-7. Although vaccination with HES conferred complete
      protection against challenge H. polygyrus infection, mAbs raised against each of
      the glycan epitopes and against VAL-1, VAL-2, and VAL-4 proteins were unable to
      do so, even though these specificities (with the exception of VAL-2) are also
      secreted by tissue-phase L4 larvae. The primary immune response in susceptible
      mice is, therefore, dominated by nonprotective Abs against a small subset of
      antigenic epitopes, raising the possibility that these act as decoy specificities
      that generate ineffective humoral immunity.

PMID- 21964032
TI  - Extracellular cysteine (Cys)/cystine (CySS) redox regulates metabotropic
      glutamate receptor 5 activity.
AB  - Extracellular cysteine (Cys)/cystine (CySS) redox potential (E(h)) has been shown
      to regulate diverse biological processes, including enzyme catalysis, gene
      expression, and signaling pathways for cell proliferation and apoptosis, and is
      sensitive to aging, smoking, and other host factors. However, the effects of
      extracellular Cys/CySS redox on the nervous system remain unknown. In this study,
      we explored the role of extracellular Cys/CySS E(h) in metabotropic glutamate
      receptor 5 (mGlu5) activation to understand the mechanism of its regulation of
      nerve cell growth and activation. We showed that the oxidized Cys/CySS redox
      state (0 mV) in C6 glial cells induced a significant increase in mGlu5-mediated
      phosphorylation of extracellular signal-regulated kinase (ERK), blocked by an
      inhibitor of mitogen-activated protein kinase (MAPK)/extracellular signal
      regulated kinase (MEK), U0126, a nonpermeant alkylating agent, 4-acetamide-4'
      maleimidylstilbene-2,2'-disulfonic acid (AMS), and a specific mGlu5 antagonist, 2
      methyl-6-(phenylethynyl)pyridine (MPEP), respectively. ERK phosphorylation under
      oxidized extracellular Cys/CySS E(h) was confirmed in mGlu5-overexpressed human
      embryonic kidney 293 (HEK293) cells. Oxidized extracellular Cys/CySS E(h) also
      stimulated the generation of intracellular reactive oxygen species (ROS) involved
      in the phosphorylation of ERK by mGlu5. Moreover, activation of mGlu5 by oxidized
      extracellular Cys/CySS E(h) was found to affect expression of NF-kappaB and
      inducible nitric oxide synthase (iNOS). The results also showed that
      extracellular Cys/CySS E(h) involved in the activation of mGlu5 controlled cell
      death and cell activation in neurotoxicity. In addition, plasma Cys/CySS E(h) was
      found to be associated with the process of Parkinson's disease (PD) in a rotenone
      induced rat model of PD together with dietary deficiency and supplementation of
      sulfur amino acid (SAA). The effects of extracellular Cys/CySS E(h) on SAA
      dietary deficiency in the rotenone-induced rat model of PD was almost blocked by
      MPEP pretreatment, further indicating that oxidized extracellular Cys/CySS E(h)
      plays a role in mGlu5 activity. Taken together, the results indicate that mGlu5
      can be activated by extracellular Cys/CySS redox in nerve cells, which possibly
      contributes to the process of PD. These in vitro and in vivo findings may aid in
      the development of potential new nutritional strategies that could assist in
      slowing the degeneration of PD.

PMID- 21964033
TI  - Impact of PGC-1alpha on the topology and rate of superoxide production by the
      mitochondrial electron transport chain.
AB  - Reactive oxygen species (ROS) play an important role in normal signaling events
      and excessive ROS are associated with many pathological conditions. The amount of
      ROS in cells is dependent on both the production of ROS by the mitochondrial
      electron transport chain and their removal by ROS-detoxifying enzymes. The
      peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha)
      is a master regulator of mitochondrial functions and a key regulator of the ROS
      detoxifying program. However, the impact of PGC-1alpha on the topology and rate
      of superoxide production by the mitochondrial electron transport chain is not
      known. We report here, using mitochondria from muscle creatine kinase-PGC-1alpha
      transgenic mice, that PGC-1alpha does not affect the topology of ROS production,
      but increases the capacity of complexes I and III to generate ROS. These changes
      are associated with increased mitochondrial respiration and content of
      respiratory chain complexes. When normalizing ROS production to mitochondrial
      respiration, we find that PGC-1alpha preserves the percentage of free radical
      leak by the electron transport chain. Together, these data demonstrate that PGC
      1alpha regulates the intrinsic properties of mitochondria in such a way as to
      preserve a tight coupling between mitochondrial respiration and ROS production.

PMID- 21964034
TI  - Measuring E(GSH) and H2O2 with roGFP2-based redox probes.
AB  - Redox biochemistry plays an important role in a wide range of cellular events.
      However, investigation of cellular redox processes is complicated by the large
      number of cellular redox couples, which are often not in equilibrium with one
      another and can vary significantly between subcellular compartments and cell
      types. Further, it is becoming increasingly clear that different redox systems
      convey different biological information; thus it makes little sense to talk of an
      overall "cellular redox state". To gain a more differentiated understanding of
      cellular redox biology, quantitative, redox couple-specific, in vivo measurements
      are necessary. Unfortunately our ability to investigate specific redox couples or
      redox-reactive molecules with the necessary degree of spatiotemporal resolution
      is very limited. The development of genetically encoded redox biosensors offers a
      promising new way to investigate redox biology. Recently developed redox
      sensitive green fluorescent proteins (roGFPs), genetically fused to redox-active
      proteins, allow rapid equilibration of the roGFP moiety with a specific redox
      couple. Two probes based on this principle are now available: Grx1-roGFP2 for the
      measurement of glutathione redox potential (E(GSH)) and roGFP2-Orp1 for measuring
      changes in H(2)O(2) concentration. Here we provide a detailed protocol for the
      use of these probes in both yeast and mammalian systems using either plate-reader
      or microscopy-based measurements.

PMID- 21964035
TI  - Differences in the genomic content of Bordetella pertussis isolates before and
      after introduction of pertussis vaccines in four European countries.
AB  - Resurgence of pertussis has been observed in many countries with high vaccination
      coverage and clonal expansion of certain Bordetella pertussis strains has been
      associated with recent epidemics in Europe. It is known that vaccinations have
      selected strains which are different from those used for vaccine production.
      However, little is known about the differences in genomic content of strains
      circulating before the vaccination was introduced. In this study, we compared the
      genomes of 39 vaccine strains and old clinical isolates (isolated 1941-1984)
      collected from Finland (n = 5), Poland (n = 14), Serbia (n = 10) and the UK (n =
      10). The analysis included genotyping, pulsed-field gel electrophoresis (PFGE)
      and comparative genomic hybridisation (CGH). Compared to the strain Tohama I, the
      European isolates analyzed have lost three major regions of difference (RD3, 5
      and 29). However, difference in frequency of the absent RDs 3 (BP0910A-BP0934), 5
      (BP1135-BP1141) or 29 (BP1225) was observed among isolates from the four
      countries. Of the isolates with absent RD5, half had also a duplicated region in
      the genome. All four RDs (RD22 (BB0535-BB0541), 23 (BB0916-BB0921), 24 (BB1140
      BB1158) and 26 (BB4880-BB4888)) absent in Tohama I were present in majority of
      the tested isolates. Results obtained from PFGE analysis correlated well with
      those of CGH. Recently a novel pertussis toxin promoter allele (ptxP3) was
      described. Isolates with ptxP3 have replaced resident ptxP1 isolates in the
      countries where this was investigated. When the recent isolates, collected in
      2000-2004, selected from the four countries were examined, the ptxP3 allele was
      found in all countries except Poland. Our result indicates that at least three
      clusters of B. pertussis circulated in Europe in pre- and early vaccine era and
      their genomes were distinct from that of the reference strain Tohama I. Although
      progressive gene loss occurs in B. pertussis population with time, difference in
      frequency of the lost genes were observed among isolates from the four countries.
      The observed differences in genomic content might be vaccine-driven.

PMID- 21964036
TI  - Effects of integrated volitional control electrical stimulation (IVES) on upper
      extremity function in chronic stroke.
AB  - We evaluated the efficacy of a novel electromyogram (EMG)-controlled electrical
      stimulation system, called the integrated volitional control electrical
      stimulator (IVES), on the recovery of upper extremity motor functions in patients
      with chronic hemiparetic stroke. Ten participants in the chronic stage (more than
      12 months post-stroke with partial paralysis of their wrist and fingers) received
      treatment with IVES to the extensor carpi radialis and extensor digitorum
      communis 6 h/day for 5 days. Before and after the intervention, participants were
      assessed using upper-extremity Fugl-Meyer motor assessment (FMA), the active
      range of motion (A-ROM), the nine-hole peg test (NHPT), and surface EMG
      recordings. The upper extremity FMA showed a statistically significant increase
      from 50.8 +/- 5.8 to 56.8 +/- 6.2 after the intervention (P < 0.01). The A-ROM of
      wrist extension was also significantly improved from 36.0 degrees  +/- 15.4
      degrees  to 45.0 degrees  +/- 15.5 degrees  (P < 0.01). The NHPT significantly
      decreased from 85.3 +/- 52.0 to 63.3 +/- 29.7 (P = 0.04). EMG measurements
      demonstrated statistically significant improvements in the coactivation ratios
      for the wrist flexor and extensor muscles after the intervention. This study
      suggested that 5 days of IVES treatment yields a noticeable improvement in upper
      extremity motor functions in patients with chronic hemiparetic stroke.

PMID- 21964037
TI  - [Slow the pace of renal failure in autosomal dominant polycystic kidney disease:
      hopes and disappointments].
AB  - Autosomal dominant polycystic kidney disease is the most frequent renal genetic
      disease. Its main complication is renal failure. Despite a better understanding
      of the mechanisms leading to cyst development and growth, no specific treatment
      is available. Inhibition of mTOR pathway was a great hope, unfortunately, two
      clinical trials failed to show a clinical benefit. Numerous new drugs are in
      clinical trials or in the pipe-line. We could hope, in the 5 years to the
      emergence of an efficient treatment to slow the pace of renal failure in ADPKD.

PMID- 21964038
TI  - [Sjogren's syndrome and non-Hodgkin's lymphoma: from pathophysiology to
      treatment].
AB  - Although infrequent, the development of non-Hodgkin's lymphoma (NHL) during the
      course of Sjogren's syndrome represents a major complication. Nethertheless, most
      NHL developing in patients with Sjogren's syndrome are B cell lymphomas involving
      the marginal zone, localized to extranodal sites. Predictive factors include
      lymphadenopathy, splenomegaly, neutropenia, cryoglobulinemia and low C4 levels.
      The treatment of B cell lymphomas depends on its nature and localization.
      Biotherapies targeting the B lymphocyte, such as rituximab, a chimeric monoclonal
      anti-CD20 antibody, or more recently targeting BAFF can be proposed.

PMID- 21964039
TI  - Simultaneous occurrence of generalized granuloma annulare, anterior uveitis and
      giant cell arteritis: coincidental or not?

PMID- 21964040
TI  - [Late-onset asthma in a traveler].

PMID- 21964041
TI  - [Face allotransplantation: experimental? Care? How does one pass from one to
      another?].

PMID- 21964042
TI  - [Venous thromboembolism risk and prophylaxis in the acute hospital care setting
      (ENDORSE study): results obtained in France].
AB  - AIM: Information about the variation in the risk for venous thromboembolism (VTE)
      and in prophylaxis practices in France and around the world is scarce. METHODS:
      The Epidemiologic International Day for the Evaluation of Patients at Risk for
      Venous Thromboembolism in the Acute Hospital Care Setting (ENDORSE) study is a
      multinational cross-sectional survey designed to assess the prevalence of VTE
      risk in the acute hospital care setting, and to determine the proportion of at
      risk patients who receive effective prophylaxis, in accordance with the 2004
      American College of Chest Physicians (ACCP) guidelines. This paper gives the
      results of the ENDORSE study in the French centres in comparison with the global
      worldwide results of the ENDORSE study and with other Western Europe countries.
      RESULTS: In France, 18 randomized hospitals participated to the study between
      august 2006 and January 2007. 2844 patients were evaluated (917 from chirurgical
      wards and 1927 from medical wards). One thousand four hundred and nineteen
      patients (49.9%) were at VTE risk (78.3% in chirurgical wards and 36.4% in
      medical wards). Of the 1419 patients at VTE risk, 62.4% received ACCP-recommended
      VTE prophylaxis (71.2% in chirurgical wards and 53.5% in medical wards). VTE
      Prophylaxis in France (62.4%) is more frequent than worldwide in the
      international ENDORSE study (50.2%) and similar to the majority of the other
      western European countries and the USA. It is also more used in university
      hospitals (66.9%) than in other hospitals (58.9%). Prophylaxis in patients at
      risk for VTE was presented in 43% patients with acute heart failure, 53% with non
      infectious acute respiratory failure, 57% in patients with pulmonary infection,
      56% in patients with stroke, 55% in patients with active cancer and 48% in
      patients with non-pulmonary sepsis. CONCLUSIONS: The ENDORSE study has shown a
      high level of patients at risk for VTE in the population of hospitalized patients
      in France. The rate of prophylaxis for VTE remained low, in particular in
      Medicine wards. Our data reinforced the rationale for the use of hospital-wide
      strategies to assess patients' VTE risk and to implement measures that ensure
      that at-risk patients receive appropriate prophylaxis, in particularly in medical
      patients.

PMID- 21964043
TI  - [Prevalence of osteoporosis in male patients with risk factors].
AB  - Male osteoporosis is often secondary to other conditions. However the causes of
      osteoporosis in men are dramatically variable according to the authors. The aim
      of this observational multicenter study was to assess the main risk factors and
      causes for male patients with low bone mineral density (LBM). METHODS: The study
      was performed in a cohort of rheumatologists who usually prescribe bone mineral
      density assessment according to HAS criteria (one or more criteria) for bone
      mineral density (BMD) measurement as defined by: (a): vertebral fracture; (b):
      non traumatic non vertebral fracture; (c): corticosteroid therapy; (d):
      hypogonadism or GnRH agonist therapy; (e): endocrine disorders; (f): osteogenesis
      imperfecta (OI). BMD was measured by dual photon absorptiometry (DXA) at lumbar
      spine, femoral or total neck sites. Osteoporosis was defined as a T-score value
      less or equal to 2.5 at one of those region of interest (ROI); LBM as a T-score
      value between -1 and -2.5. RESULTS: A total of 431 rheumatologists included 1198
      male patients (66.6 +/- 12.2 years). According to DXA results, 888 patients (74.1
      %) had osteoporosis and 231 (19.3 %) had osteopenia. BMD was considered as normal
      for 79 patients (6.6 %). A total of 1146 patients (95.7 %) satisfied to the
      criteria of reimbursement of DXA measurement. Six hundred and eighty-six patients
      (57.3 %) had suffered from vertebral fractures and 349 patients (29.2 %) from non
      vertebral fractures. Corticosteroids had been prescribed in 28.7 % of patients
      and 6.6 % were treated with GnRH agonists for prostate cancer. Hypogonadism was
      diagnosed in 27 %. Five patients suffered from OI. Other risk factors were
      detected: alcoholism and smoking in 28.1 % and 42.9 % respectively; rheumatoid
      arthritis or spondylarthropathy in 12.5 % of patients; chronic pulmonary
      disorders in 16.1 %. By contrast endocrinopathies were rare (2.5 %). Several risk
      factors were more frequently encountered for patients with osteoporosis as
      compared with osteopenia, i.e., smoking, alcohol abuse, low calcium intake,
      vitamin D insufficiency and maternal history of hip fracture. CONCLUSION: A
      diagnosis of osteoporosis (BMD <= 2.5) was established by rheumatologists in 74.1
      % of patients with clinical risk factors: LBM was found in 93.4 %. In 95.7 % the
      criteria for reimbursement of DXA measurement were satisfied. DXA is useful in
      male patients with classical risk factors of osteoporosis to confirm the
      diagnosis of the disease and start a treatment.

PMID- 21964044
TI  - [The evolution of kidney transplantation over the last 20 years].
AB  - Kidney transplantation is an efficient treatment of end stage renal disease,
      decreasing patient mortality by comparison with mortality in dialysis and
      improving patient quality of life. The number of patients living in France with a
      functioning transplant is almost as high as the number of patients on dialysis
      (33,000 versus 37,500 in 2009). The constant progress in immunosuppressive
      treatments has made graft survival improve. According to the "Agence de
      biomedecine", the national institution in charge of transplantation regulation
      and management, overall graft survival is 68% at 10 years but 80% for living
      donor transplantation. Transplantation indications have been extended with time
      to more difficult patients: retransplanted patients and elderly patients, to the
      point that age per se is no more a contraindication to transplantation. Increase
      in transplant activity has followed increase in kidney harvesting in marginal
      donors, called "extended criteria donors": older, hypertensive, having
      atherosclerotic pathologies. Kidney from these donors are attributed to
      recipients of similar age. With organ shortage, new sources of donors are
      proposed, non heart beating donors and living donors. Living donor
      transplantation is the best transplantation with the best results but it is
      insufficiently developed in France (8-10% of the total annual number of renal
      transplantations versus 30-50% in the Scandinavian and Anglo-Saxon countries).
      Extension of the definition of the living donor through the successive revisions
      of the Law of Bioethics should hopefully improved this situation.

PMID- 21964045
TI  - Modulation of the ERP repetition effects during exposure to phobia-relevant and
      other affective pictures in spider phobia.
AB  - In the present study, dense sensor event-related potentials were measured in
      spider-phobic individuals and non-anxious controls during incidental encoding of
      phobia-relevant spider and standard neutral, unpleasant and pleasant pictures.
      Stimulus repetition effects were assessed by presenting each picture twice--in
      the first and in the second half of the session. Repeated presentation of
      standard pleasant, unpleasant and neutral pictures resulted in a late ERP
      repetition effect that was similarly pronounced in both experimental groups and
      for all picture categories. Moreover, relative to non-fearful controls spider
      phobic individuals showed an overall greater early ERP repetition effect starting
      at 180 ms after picture onset. At later stages of evaluative processing, repeated
      as compared with initial presentation of phobia-relevant spider pictures elicited
      reduced ERP amplitudes over centro-parietal sites (480-580 ms) in spider-phobic
      but not in control individuals. This pattern of results indicates that in small
      animal phobics long lasting exposure to their feared pictures leads to an
      increased mobilization of the perceptual analysis system, an effect that might
      help to improve emotional control and/or facilitate strategic avoidance of threat
      resulting in a diminished evaluative threat processing. This phobia-specific
      processing mechanism might prevent effective stimulus processing and hinder the
      habituation process during treatment.

PMID- 21964046
TI  - Accumbal dopamine function in postpartum rats that were raised without their
      mothers.
AB  - Postpartum rats that had been previously raised in an artificial rearing (AR)
      apparatus, without their mothers or siblings during the preweaning period, show
      altered maternal responses towards their own offspring in adulthood. In mother
      reared (MR) rats, nucleus accumbens (NAC) dopamine (DA) responses to pups evoke a
      robust sustained rise during the postpartum period and following treatment with
      estrogen/progesterone parturient-like hormones (Afonso et al., 2009). These MR
      females had siblings that received AR rearing with varying amounts of preweaning
      tactile stimulation (ARmin; ARmax). The present study examined NACshell DA
      responses to pup and food stimuli in these AR rats, and statistically compared
      them to their MR siblings. Microdialysis samples were collected from adult (90
      days postnatal) AR females in different parity states (cycling vs. postpartum,
      Exp. 1), or after ovariectomy with different hormone treatments (sham vs.
      hormone, Exp. 2. After basal sample collection, pup and then food stimuli were
      individually presented to the females in the dialysis chamber. As with their MR
      siblings, basal DA concentrations were lower and pup-evoked DA responses greater
      in hormonally-primed AR females than in non-primed AR controls. Compared to their
      postpartum MR sisters (Exp. 1), AR rats had increased basal DA levels, reduced
      pup related DA elevations, and disrupted maternal behavior. The postpartum AR
      impairment in pup-evoked DA was reversed by additional pre-weaning tactile
      stimulation. Exogenous hormones (Exp. 2) eliminated AR impairments on pup-evoked
      DA responses. Although MR and AR siblings had comparable DA responses to food
      stimuli, upon reanalyzing MR data it was found that only postpartum dams had DA
      responses to pups greater than to food. These data suggest that that the
      hormonally induced suppression of basal DA levels may reflect saliency of pups
      which was greater in MR than in AR dams. Preweaning tactile stimulation could
      partially reverse these effects only in naturally cycling or parturient animals.

PMID- 21964047
TI  - Implications of long-term medication of oral steroids and antimalarial drugs in
      primary Sjogren's syndrome.
AB  - BACKGROUND: Immunomodulating drugs are commonly used in treating patients with
      autoimmune diseases but with very different outcomes. We aimed to investigate
      differences in cytokine and autoantibody levels with regard to patient
      characteristics in patients with primary Sjogren's syndrome (pSS) receiving oral
      steroids or antimalarial drugs (AM) after a longer period of time. METHODS: Serum
      samples from 141 patients fulfilling the revised EU-US criteria and 99 healthy
      controls were analysed for 25 cytokines and 8 autoantibodies. RESULTS: AM
      patients had lowered levels of IL-5, IL-10, IL-13 and IFN-gamma, though non
      significantly. Use of prednisolone was associated with reduced levels of IL-15,
      IL-2, IL-4, IL-12p40, TNF-alpha, MIP-1alpha and MIP-1beta (p<0.05), and a trend
      towards decreased levels of IL-1RA and IL-1beta was observed. No associations
      were seen between AM and antibody levels. Significantly higher protein levels of
      anti-Ro-52 and anti-Ro-60 were observed in the patients taking prednisolone
      (p<0.05). The proportion of patients positive for anti-Ro-52 and anti-La-48 did
      not differ significantly in the groups taking and not taking prednisolone, but a
      difference was seen for anti-Ro-60 (p<0.05). CONCLUSIONS: Prednisolone is a
      potent anti-inflammatory and immunosuppressive drug commonly used in autoimmune
      diseases. Our study shows that oral steroids are associated with reduced levels
      of several pro-inflammatory cytokines, but increased levels of pSS specific
      autoantibodies. The association between steroid use and increased antibody levels
      is not readily explained by known steroid effects, and should therefore be
      confirmed in further studies. Lower levels of pro-inflammatory cytokines indicate
      a beneficial effect of oral steroids in this patient group.

PMID- 21964048
TI  - The functional expression of TLR3 in EPCs impairs cell proliferation by induction
      of cell apoptosis and cell cycle progress inhibition.
AB  - Toll-like receptor 3 (TLR3), a member of the TLR family that recognizes double
      stranded RNA (dsRNA), plays an important role in antiviral immunity. TLR3 is
      widely expressed in various cells and the activation of TLR3 induces cell
      apoptosis in some cells. However, the effect of TLR3 on cell proliferation in
      endothelial progenitor cells (EPCs) is unclear. In this study, we found that EPCs
      expressed high levels of TLR1, 3, 4, and 6 and low levels of TLR2, 5, 7, 8, and
      10. The treatment of EPCs with TLR3 agonist Poly I:C up-regulated the expression
      of cytokines IL-1beta, IL-6, IL-8, TNF-alpha, IFN-alpha, and IFN-beta, indicating
      that EPCs expressed functional TLR3. Moreover, Poly I:C treatment induced cell
      cycle progress inhibition and cell apoptosis, leading to the inhibition of cell
      proliferation. Further studies indicated that IL-1beta was involved in TLR3
      induced cell proliferation inhibition, as IL-1beta inhibited cell proliferation
      in a dose-dependent manner, and the IL-1beta receptor type I (IL-1R1)
      neutralizing antibody ameliorated Poly I:C-induced cell proliferation inhibition.
      Taken together, these results suggest that Poly I:C impairs cell proliferation by
      inducing cell cycle progress inhibition and cell apoptosis via TLR3 in EPCs.

PMID- 21964049
TI  - A 22 year follow-up study on lymphatic filariasis in Tanzania: analysis of
      immunological responsiveness in relation to long-term infection pattern.
AB  - Seventy-one individuals who had been examined for Wuchereria bancrofti
      microfilaraemia in 1975, some of whom had been offered mass treatment with
      diethylcarbamazine (DEC) in subsequent years, were re-identified in 1996 and
      examined for microfilaraemia, circulating filarial antigenemia and cellular and
      humoral immunoresponsiveness to crude antigen homogenates prepared from Brugia
      pahangi parasite material. 85.9% of the study individuals had the same infection
      status in 1975 and 1996, suggesting strong predisposition to infection over
      extended periods of time. IL-4, IL-5 and IFNgamma responses were associated with
      being infection negative in 1996 whereas IL-10 responses were associated with
      being infection positive. Similarly, specific IgG3 and IgE were strongly
      associated with being infection negative in 1996 whereas specific IgG4, and thus
      high IgG4/IgE ratios, were strongly associated with being infection positive.
      Intermediary levels of mainly IL-5, IFNgamma and PBMC stimulation indices were
      observed for study individuals who changed from being infection positive in 1975
      to infection negative in 1996, or vice versa, suggesting a transition in cellular
      immunoresponsiveness associated with changing infection status. The findings
      suggest that some people are more disposed to infection with bancroftian
      filariasis than others and that this is largely unaffected by treatment with DEC.
      The findings also suggest that specific cellular and antibody responses are more
      related to current than past infection status, and that IL-4, IL-5, IFNgamma,
      specific IgG3 and IgE are associated with parasite clearance, whereas IL-10 and
      specific IgG4 are associated with parasite protection.

PMID- 21964050
TI  - Transmission of Leishmania infantum MON-98 to hamsters by the bite of Phlebotomus
      langeroni Nitzulescu (Diptera: Psychodidae).
AB  - The ability of Phlebotomus langeroni to successfully acquire and transmit
      Leishmania infantum MON-98 to hamsters was demonstrated. Sand flies and
      Leishmania both originated from an infantile visceral leishmaniasis focus in El
      Agamy Egypt. P. langeroni females were infected by feeding on lesions of needle
      inoculated hamster and on infected blood suspension using a chick-skin membrane
      apparatus. Infection rate of sand flies fed on membrane was 88% compared to 7.8%
      for flies fed on leishmanial lesion. The transmission to hamster took place by
      the bites of infective flies taking a second blood meal, on the 8th to 10th day
      post-feeding. Furthermore, successful transmission was by the bites of flies that
      took no blood or that took full blood meal. Whereas flies that took full blood
      meal were not infective as indicated by dissection. In three hamsters, lesions
      developed after three months. Leishmania amastigotes were demonstrated from the
      lesion as well as from the liver and spleen of infected hamsters.

PMID- 21964051
TI  - Why does older adults' balance become less stable when walking and performing a
      secondary task? Examination of attentional switching abilities.
AB  - Previous research using dual-task paradigms indicates balance-impaired older
      adults (BIOAs) are less able to flexibly shift attentional focus between a
      cognitive and motor task than healthy older adults (HOA). Shifting attention is a
      component of executive function. Task switch tests assess executive attention
      function. This multivariate study asked if BIOAs demonstrate greater task
      switching deficits than HOAs. A group of 39 HOA (65-80 years) and BIOA (65-87
      years) subjects performed a visuo-spatial task switch. A sub-group of subjects
      performed a dual-task obstacle avoidance paradigm. All participants completed the
      Berg Balance Scale (BBS) and Timed Up and Go (TUG). We assessed differences by
      group for: (1) visuo-spatial task switch reaction times (switch/no-switch), and
      performance on the BBS and TUG. Our balance groups differed significantly on BBS
      score (p<.001) and switch reaction time (p=.032), but not the TUG. This confirmed
      our hypothesis that neuromuscular and executive attention function differs
      between these two groups. For our BIOA sub-group, gait velocity correlated
      negatively with performance on the switch condition (p=.036). This suggests that
      BIOA efficiency of attentional allocation in dual task settings should be further
      explored.

PMID- 21964052
TI  - Increased plantar foot pressure in persons affected by leprosy.
AB  - Although foot pressure has been reported to be increased in people affected by
      leprosy, studies on foot pressure and its determinants are limited. Therefore,
      the aim was to assess barefoot plantar foot pressure and to identify clinical
      determinants of increased plantar foot pressure in leprosy affected persons.
      Plantar pressure in both feet was assessed using the Novel EMED-X platform in 39
      persons affected by leprosy. Peak pressure was determined for the total foot and
      four regions: hallux, metatarsal heads, midfoot and heel. Potential determinants
      were: age, weight, nerve function (Neuropathy Disability Score, Pressure
      Perception Threshold and Vibration Perception Threshold), toe and foot
      deformities, joint mobility, ankle muscle strength and callus. Increased peak
      pressure (>600kPa) was observed in 46% of the participants. The highest peak
      pressure (mean) was found in the metatarsal heads region (right 549 (SD 321)kPa;
      left 530 (SD 298)kPa). Multilevel regression analysis showed that Neuropathy
      Disability Score, amputation/absorption of toes and hallux valgus independently
      contributed to metatarsal heads peak pressure in persons affected with leprosy.
      To conclude, peak pressure is increased in people affected by leprosy. The
      highest peak pressure is found in the forefoot region and is significantly
      associated to Neuropathy Disability Score, toe amputation/absorption and hallux
      valgus. Screening for clinical characteristics can be used to identify individual
      persons affected by leprosy at risk of excessive pressure.

PMID- 21964053
TI  - Gait and cognition: the relationship between gait stability and variability with
      executive function in persons with and without dementia.
AB  - Besides cognitive decline, dementia is characterized by gait changes and
      increased fall risk, also in early stages of the disease. The aim of this study
      was to investigate differences in the relationship between executive function and
      gait variability and stability during single task and dual task walking in
      persons with and without dementia. The study sample consisted of three groups:
      fifteen dementia patients (aged 75-87), fourteen healthy elderly (aged 75-85),
      and twelve relatively younger elderly (aged 55-70). Participants underwent
      neuropsychological testing and tests of single and dual task walking while
      wearing an accelerometer. Outcome measures include stride related measures such
      as mean and coefficient of variation of stride time, and dynamic measures
      regarding the magnitude, smoothness, predictability and local stability of trunk
      accelerations. Patients with dementia exhibited a significantly (p<.05) less
      variable, but more irregular trunk acceleration pattern than cognitively intact
      elderly on single and dual task walking. The walking pattern during dual tasking
      for the whole group became increasingly unstable, even though participants
      modified their gait pattern by slowing their walking speed, and decreasing the
      magnitude of trunk accelerations. Moderate to high correlations (r>.51) were
      found between executive tasks and gait parameters. In conclusion, these findings
      indicate that decreased executive function plays an important role in increased
      gait variability in dementia patients; a fact that should be considered when
      designing fall risk interventions for this population. Furthermore, results
      indicate that measures of gait variability and stability should be deemed
      worthwhile in the diagnosis of dementia.

PMID- 21964055
TI  - Pre-clinical evaluation of a 15-valent pneumococcal conjugate vaccine (PCV15
      CRM197) in an infant-rhesus monkey immunogenicity model.
AB  - The incidence of invasive pneumococcal disease (IPD), caused by the approximately
      91 serotypes of Streptococcus pneumoniae (PN), varies geographically and
      temporally as a result of changing epidemiology and vaccination patterns as well
      as due to regional measurement differences. Prevnar((r)) (Pfizer), the first
      licensed pneumococcal conjugate vaccine (PCV), comprises polysaccharides (PS)
      from 7 serotypes conjugated to the mutant diphtheria toxin carrier protein,
      CRM197. In the United States and elsewhere, this vaccine has been highly
      efficacious in reducing the incidence of IPD caused by vaccine serotypes,
      however, the incidence of non-vaccine serotypes (e.g., 19A, 22F, and 33F) has
      increased, resulting in the need for vaccines with higher valencies. In response,
      10- and 13-valent PCVs have recently been licensed. To further increase serotype
      coverage, we have developed a 15-valent PCV containing PS from serotypes 1, 3, 4,
      5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F and 33F conjugated to CRM197 and
      formulated on aluminum phosphate adjuvant. Vaccine immunogenicity was evaluated
      in infant rhesus monkeys since they, like human infants, respond poorly to
      unconjugated PN PS. Infant (2-3 month old) rhesus monkeys were vaccinated three
      times with PCV-15 or Prevnar((r)) at 2 month intervals, and serotype-specific IgG
      antibodies were measured using a multiarray electrochemiluminescence (ECL) assay.
      The results indicate that antibody responses to PCV-15 and Prevnar((r)) were
      comparable for the 7 common serotypes and that post-vaccination responses to PCV
      15 were >10-fold higher than baseline for the 8 additional serotypes.

PMID- 21964056
TI  - Estimating the age-specific duration of herpes zoster vaccine protection: a
      matter of model choice?
AB  - INTRODUCTION: The estimation of herpes zoster (HZ) vaccine efficacy by time since
      vaccination and age at vaccination is crucial to assess the effectiveness and
      cost-effectiveness of HZ vaccination. Published estimates for the duration of
      protection from the vaccine diverge substantially, although based on data from
      the same trial for a follow-up period of 5 years. Different models were used to
      obtain these estimates, but it is unclear which of these models is most
      appropriate (if any). Only one study estimated vaccine efficacy by age at
      vaccination and time since vaccination combined. Recently, data became available
      from the same trial for a follow-up period of 7 years. AIM AND METHODS: We aim to
      elaborate on estimating HZ vaccine efficacy (1) by estimating it as a function of
      time since vaccination and age at vaccination, (2) by comparing the fits of a
      range of models, and (3) by fitting these models on data for a follow-up period
      of 5 and 7 years. RESULTS: Although the models' fit to data are very comparable,
      they differ substantially in how they estimate vaccine efficacy to change as a
      function of time since vaccination and age at vaccination. DISCUSSION: An
      accurate estimation of HZ vaccine efficacy by time since vaccination and age at
      vaccination is hampered by the lack of insight in the biological processes
      underlying HZ vaccine protection, and by the fact that such data are currently
      not available in sufficient detail. Uncertainty about the choice of model to
      estimate this important parameter should be acknowledged in cost-effectiveness
      analyses.

PMID- 21964057
TI  - "Once I begin to participate, people will run away from me": understanding stigma
      as a barrier to HIV vaccine research participation in Kenya.
AB  - PURPOSE: Participation of volunteers in clinical research is essential to the
      development of effective HIV prevention methods, including an HIV vaccine. This
      study expands current knowledge of stigma and discrimination related to
      participation in HIV vaccine research in sub-Saharan Africa by exploring the
      perception of stigma and discrimination as a barrier to participation in HIV
      vaccine research in Kenya. METHODS: Eighteen focus groups with a total of 133
      participants and 82 individual interviews were conducted with a range of
      respondents at two centers in Nairobi, Kenya: a preventive AIDS vaccine trial
      center; and a preparatory clinical and epidemiological study center. Respondents
      included peer leaders, community advisory board members, former and current
      volunteers in clinical research, study staff, community leaders and community
      members. Data were analyzed using an iterative coding process. RESULTS: Four
      prominent stigma-related barriers to participation emerged among all respondent
      groups, across both centers: (1) volunteers are often assumed by family and
      community members to be HIV positive because of their participation in vaccine
      research; (2) HIV-related stigma is perceived as pervasive and damaging in the
      communities where volunteers live, thus they fear consequent stigma if people
      believe them to be HIV positive; (3) potential volunteers fear being tested for
      HIV, a prerequisite for participation, because of possible disclosure of HIV
      status in communities with high perceived HIV-related stigma; and (4) volunteers
      must carefully manage information about their participation because of
      misperceptions and assumptions about vaccine research volunteers. CONCLUSIONS:
      HIV-related stigma and discrimination influence people's decisions to join HIV
      vaccine related research. Findings underscore a need for integration of stigma
      reduction programming into education and outreach activities for volunteers, and
      the communities in which they live. This is particularly critical for trials
      recruiting individuals with higher HIV risk, who are often already highly
      stigmatized.

PMID- 21964058
TI  - Vaccination policies for health-care workers in acute health-care facilities in
      Europe.
AB  - The aim of this study was to evaluate existing policies regarding recommended and
      mandatory occupational vaccinations for health-care workers (HCWs) in Europe. A
      standardized questionnaire was sent to experts in Infection Control or
      Occupational Health in all 27 European Union Member States, as well as Norway,
      Russia, and Switzerland. All 30 countries have established policies about HCW
      vaccination against vaccine-preventable diseases. However significant gaps and
      considerable country-to-country variation were found, in terms of number of
      recommended vaccines and target subgroups of HCWs and health-care settings.
      Vaccination against hepatitis B and annual vaccination against seasonal influenza
      are almost universally recommended for HCWs in Europe (29 countries each,
      including eight countries where vaccination against hepatitis B is mandatory or
      required for employment). Policies regarding HCW vaccination also exist against
      mumps (12 countries), measles or rubella (15 countries), varicella (17
      countries), diphtheria-tetanus (14 countries), pertussis (9 countries),
      poliomyelitis (11 countries), hepatitis A (11 countries), tuberculosis (BCG
      vaccine) (9 countries), and against meningococcus group C or meningococci groups
      A, C, W135, Y (tetravalent vaccine) (in 4 countries each). Re-evaluation of
      occupational vaccine policies for HCWs in Europe on a consensus basis is
      imperative in order to promote HCW and patient safety.

PMID- 21964059
TI  - Clonal replacement among 19A Streptococcus pneumoniae in Massachusetts, prior to
      13 valent conjugate vaccination.
AB  - As part of an ongoing study of the response of the Streptococcus pneumoniae
      population to conjugate vaccination, we applied multi-locus sequence typing
      (MLST) to 291 isolates sampled from nasopharyngeal carriage in Massachusetts
      children. We found 94 distinct sequence types (STs), including 19 that had not
      been previously recorded, and a xpt allele containing a large insertion.
      Comparison with a similar sample collected in 2007 revealed no significant
      overall difference in the ST composition (p=0.51) suggesting that the population
      has reached a new equilibrium following the introduction of 7 valent vaccination
      in 2000. Within serotypes, a large and statistically significant increase
      (p=0.014 Fisher's Exact test) was noted in the prevalence of the major
      multiresistant clone ST 320, which is apparently outcompeting ST 199 among
      serotype 19A strains. This sample will be used as a baseline to study the future
      evolution of the pneumococcal population in Massachusetts following introduction
      of vaccines with higher valency.

PMID- 21964054
TI  - Cancer vaccines and carbohydrate epitopes.
AB  - Tumor-associated carbohydrate antigens (TACA) result from the aberrant
      glycosylation that is seen with transformation to a tumor cell. The carbohydrate
      antigens that have been found to be tumor-associated include the mucin related
      Tn, Sialyl Tn, and Thomsen-Friedenreich antigens, the blood group Lewis related
      Lewis(Y), Sialyl Lewis(X) and Sialyl Lewis(A), and Lewis(X) (also known as stage
      specific embryonic antigen-1, SSEA-1), the glycosphingolipids Globo H and stage
      specific embryonic antigen-3 (SSEA-3), the sialic acid containing
      glycosphingolipids, the gangliosides GD2, GD3, GM2, fucosyl GM1, and Neu5GcGM3,
      and polysialic acid. Recent developments have furthered our understanding of the
      T-independent type II response that is seen in response to carbohydrate antigens.
      The selection of a vaccine target antigen is based on not only the presence of
      the antigen in a variety of tumor tissues but also on the role this antigen plays
      in tumor growth and metastasis. These roles for TACAs are being elucidated. Newly
      acquired knowledge in understanding the T-independent immune response and in
      understanding the key roles that carbohydrates play in metastasis are being
      applied in attempts to develop an effective vaccine response to TACAs. The role
      of each of the above mentioned carbohydrate antigens in cancer growth and
      metastasis and vaccine attempts using these antigens will be described.

PMID- 21964060
TI  - Can the response to 23-valent pneumococcal vaccine in splenectomised patients be
      predicted?
AB  - The 23-valent pneumococcal vaccine has unequal effectiveness in splenectomised
      patients. We performed a longitudinal study (2005-2008) whose main objective was
      to characterize the profile of non-responders among splenectomised patients
      treated at our institution and identify potential predictive indicators of the
      response to the vaccine. The immune response was evaluated in 96 subjects. The
      proportion of responders was 70% (95% CI: 60-78%). Immunosuppression (OR=3.19,
      95% CI 1.04-9.73) and the reason for splenectomy (hematologic neoplasia versus
      non-malignant hematologic diseases, OR=7.37, 95% CI 1.71-31.7) were independent
      predictors of non-response to vaccination. However, the positive predictive value
      of the model and the likelihood ratio for a positive result were low (PPV=76.6%,
      95% CI 66.2-84.4%, LR(+)=1.41, 95% CI 1.08-1.86). We recommend determining the
      response to pneumococcal vaccine in these patients when possible.

PMID- 21964062
TI  - Protor-2 interacts with tristetraprolin to regulate mRNA stability during stress.
AB  - The A/U-rich RNA-binding protein tristetraprolin (TTP) is an mRNA destabilizing
      factor which plays a role in the regulated turnover of many transcripts encoding
      proteins involved in immune function and cell growth control. TTP also plays a
      role in stress-induced destabilization of mRNAs. Here we report the interaction
      of TTP with a component of the mTORC2 kinase, Protor-2 (PRR5-L, protein
      Q6MZQ0/FLJ14213/CAE45978). Protor-2 is structurally similar to human PRR5 and has
      been demonstrated to bind mTORC2 via Rictor and/or Sin1 and may signal downstream
      events promoting apoptosis. Protor-2 dissociates from mTORC2 upon hyperactivation
      of the kinase and is not required for mTORC2 integrity or activity. We identified
      Protor-2 in a yeast two-hybrid screen as a TTP interactor using the C-terminal
      mRNA decay domain of TTP as bait. The interaction of Protor-2 with TTP was also
      confirmed in vivo in co-immunoprecipitation experiments and Protor-2 was also
      detected in immunoprecipitates of Rictor. Protor-2 was shown to stimulate TTP
      mediated mRNA turnover of several TTP-associated mRNAs (TNF-alpha, GM-CSF, IL-3
      and COX-2) in Jurkat cells when overexpressed while the half-lives of transcripts
      which do not decay via a TTP-mediated mechanism were unaffected. Knockdown of
      Protor-2 via RNAi inhibited TTP-mediated mRNA turnover of these TTP-associated
      mRNAs and inhibited association of TTP with cytoplasmic stress granules (SG) or
      mRNA processing bodies (P-bodies) following induction of the integrated stress
      response. These results suggest that Protor-2 associates with TTP to accelerate
      TTP-mediated mRNA turnover and functionally links the control of TTP-regulated
      mRNA stability to mTORC2 activity.

PMID- 21964063
TI  - Lack of amino acids in mouse hepatocytes in culture induces the selection of
      preneoplastic cells.
AB  - Protein malnutrition occurs when there is insufficient protein to meet metabolic
      demands. Previous works have indicated that cycles of protein fasting/refeeding
      enhance the incidence of early lesions during chemical carcinogenesis in rat
      liver. The general objective of this work was to study the effect of aminoacids
      (Aa) deprivation on the proliferation and survival of hepatocytes, to understand
      its possible involvement in the generation of pre-neoplastic stages in the liver.
      Lack of Aa in the culture medium of an immortalized mice hepatocyte cell line
      induced loss in cell viability, correlating with apoptosis. However, a
      subpopulation of cells was able to survive, which showed a more proliferative
      phenotype and resistance to apoptotic stimuli. Escaping to Aa deprivation-induced
      death is coincident with an activated mTOR signaling and higher levels of phospho
      AKT and phospho-ERKs, which correlated with increased activation of EGFR/SRC
      pathway and overexpression of EGFR ligands, such as TGF-alpha and HB-EGF. Lack of
      Aa induced a rapid increase in reactive oxygen species (ROS) production. However,
      cells that survived showed an enhancement in the levels of reduced glutathione
      and a higher expression of gamma-GCS, the regulatory enzyme of glutathione
      synthesis, which can be interpreted as an adaptation of the cells to counteract
      the oxidative stress. In conclusion, results presented in this paper indicate
      that it is possible to isolate a subpopulation of hepatocytes that are able to
      grow in the absence of Aa, showing higher capacity to proliferate and survive,
      reminiscent of a preneoplastic phenotype.

PMID- 21964064
TI  - Allosteric modulation by protein kinase Cepsilon leads to modified responses of
      EGF receptor towards tyrosine kinase inhibitors.
AB  - Recently, we described a novel function of over-expressed protein kinase Cepsilon
      (PKCepsilon) as a negative allosteric modulator of EGFR signalling in several
      head and neck squamous carcinoma (HNSCC) cell lines. Extending this work, here we
      present several lines of evidence for the potency of PKCepsilon to differently
      modulate the efficacy of EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib
      and lapatinib. Using the HNSCC cell line FaDu as a model, we demonstrate by co
      immunoprecipitation the physical association of over-expressed PKCepsilon with
      the EGFR which is stabilised by gefitinib and leads to an increase in gefitinib
      induced inhibition of EGFR downstream signalling and elevated EGFR-ErbB2
      heterodimerisation. Cell cycle and Western blot analysis revealed that the
      gefitinib-induced apoptosis was enhanced whereas the pro-apoptotic effect of
      lapatinib that requires another EGFR conformation was reduced by PKCepsilon. Our
      findings suggest that due to elevated expression PKCepsilon may associate with
      the EGFR resulting in conformational changes and different allosteric modulation
      of the EGFR behaviour towards TKIs. This surprising capacity indicates PKCepsilon
      as a novel predictive marker protein in molecular cancer therapy with EGFR
      tyrosine kinase inhibitors.

PMID- 21964065
TI  - Domain-dependent modulation of insulin-induced AS160 phosphorylation and glucose
      uptake by Ca2+/calmodulin-dependent protein kinase II in L6 myotubes.
AB  - In skeletal muscle, the molecular mechanisms by which insulin stimulates glucose
      transport remains incompletely understood. Our study investigated the cellular
      dynamics of intracellular Ca(2+) mobilisation and Ca(2+)/calmodulin-dependent
      protein kinase II (CaMKII) activation on insulin-induced skeletal muscle glucose
      transport. L6 myotubes were treated without or with insulin [100 nM] for 15 min
      and subsequently monitored for glucose uptake using isotope-labelled 2
      deoxyglucose (I-2DOG), intracellular Ca(2+) (Ca(i)(2+)) release using Fluo-4AM
      and protein phosphorylation using Western blotting. Acute exposure of myotubes to
      insulin increased both Akt substrate-160 kDa (AS160) phosphorylation and I-2DOG
      uptake. Insulin concurrently increased Ca(i)(2+) and activated CaMKII. Exposing
      myotubes to either BAPTA/AM to sequester Ca(i)(2+) or KN-93 to inhibit CaMKII
      activity, decreased insulin-induced glucose uptake without affecting AS160
      phosphorylation. On the other hand, blocking either calmodulin or the
      autoregulatory domain of CaMKII blocked the effect of insulin on both AS160
      phosphorylation and glucose transport. Likewise, genetic knockdown of CaMKII in
      myotubes using siRNA completely abolished insulin-mediated glucose uptake. These
      results illustrate impairments in Ca(i)(2+) mobilisation and CaMKII activation
      are sufficient to negatively influence insulin-dependent glucose transport by L6
      myotubes. Additionally, our results show for the first time that Ca(i)(2+) and
      domain-dependent CaMKII signalling differentially affect insulin-induced AS160
      phosphorylation, and establish that Ca(2+) and CaMKII are components of the
      insulin signalling pathway in L6 myotubes.

PMID- 21964066
TI  - The p53-p21WAF1 checkpoint pathway plays a protective role in preventing DNA
      rereplication induced by abrogation of FOXF1 function.
AB  - We previously identified FOXF1 as a potential tumor suppressor gene with an
      essential role in preventing DNA rereplication to maintain genomic stability,
      which is frequently inactivated in breast cancer through the epigenetic
      mechanism. Here we further addressed the role of the p53-p21(WAF1) checkpoint
      pathway in DNA rereplication induced by silencing of FOXF1. Knockdown of FOXF1 by
      small interference RNA (siRNA) rendered colorectal p53-null and p21(WAF1)-null
      HCT116 cancer cells more susceptible to rereplication and apoptosis than the wild
      type parental cells. In parental HCT116 cells with a functional p53 checkpoint,
      the p53-p21(WAF1) checkpoint pathway was activated upon FOXF1 knockdown, which
      was concurrent with suppression of the CDK2-Rb cascade and induction of G(1)
      arrest. In contrast, these events were not observed in FOXF1-depleted HCT116-p53
      /- and HCT116-p21-/- cells, indicating that the p53-dependent checkpoint function
      is vital for inhibiting CDK2 to induce G(1) arrest and protect cells from
      rereplication. The pharmacologic inhibitor (caffeine) of ataxia telangiectasia
      mutated (ATM) and ataxia telangiectasia and Rad3 related (ATR) protein kinases
      abolished activation of the p53-p21(WAF1) pathway upon FOXF1 knockdown,
      suggesting that suppression of FOXF1 function triggered the ATM/ATR-mediated DNA
      damage response. Cosilencing of p53 by siRNA synergistically enhanced the effect
      of FOXF1 depletion on the stimulation of DNA rereplication and apoptosis in wild
      type HCT116. Finally, we show that FOXF1 expression is predominantly silenced in
      breast and colorectal cancer cell lines with inactive p53. Our study demonstrated
      that the p53-p21(WAF1) checkpoint pathway is an intrinsically protective
      mechanism to prevent DNA rereplication induced by silencing of FOXF1.

PMID- 21964067
TI  - Functional interactions between the oxytocin receptor and the beta2-adrenergic
      receptor: implications for ERK1/2 activation in human myometrial cells.
AB  - The Gq-coupled oxytocin receptor (OTR) and the Gs-coupled beta(2)-adrenergic
      receptor (beta(2)AR) are both expressed in myometrial cells and mediate uterine
      contraction and relaxation, respectively. The two receptors represent important
      pharmacological targets as OTR antagonists and beta(2)AR agonists are used to
      control pre-term uterine contractions. Despite their physiologically antagonistic
      effects, both receptors activate the MAP kinases ERK1/2, which has been
      implicated in uterine contraction and the onset of labor. To determine the
      signalling pathways involved in mediating the ERK1/2 response, we assessed the
      effect of blockers of specific G protein-associated pathways. In human myometrial
      hTERT-C3 cells, inhibition of Galphai as well as inhibition of the Galphaq/PKC
      pathway led to a reduction of both OTR- and beta(2)AR-mediated ERK1/2 activation.
      The involvement of Galphaq/PKC in beta(2)AR-mediated ERK1/2 induction was
      unexpected. To test whether the emergence of this novel signalling mechanism was
      dependent on OTR expression in the same cell, we conducted experiments in HEK 293
      cells that were transfected with the beta(2)AR alone or co-transfected with the
      OTR. Using this approach, we found that beta(2)AR-mediated ERK1/2 responses
      became sensitive to PKC inhibition only in cells co-transfected with the OTR.
      Inhibitor studies indicated the involvement of an atypical PKC isoform in this
      process. We confirmed the specific involvement of PKCzeta in this pathway by
      assessing PKCzeta translocation to the cell membrane. Consistent with our
      inhibitor studies, we found that beta(2)AR-mediated PKCzeta translocation was
      dependent on co-expression of OTR. The present demonstration of a novel beta(2)AR
      coupled signalling pathway that is dependent on OTR co-expression is suggestive
      of a molecular interaction between the two receptors.

PMID- 21964068
TI  - Nuclear retention of importin alpha coordinates cell fate through changes in gene
      expression.
AB  - Various cellular stresses including oxidative stress induce a collapse of the Ran
      gradient, which causes accumulation of importin alpha in the nucleus and a
      subsequent block of nuclear protein import. However, it is unknown whether
      accumulated importin alpha performs roles in the nucleus after its migration in
      response to stress. In this study, we found that nuclear-retained importin alpha2
      binds with DNase I-sensitive nuclear component(s) and exhibits selective
      upregulation of mRNA encoding Serine/threonine kinase 35 (STK35) by microarray
      analysis. Chromatin immunoprecipitation and promoter analysis demonstrated that
      importin alpha2 can access to the promoter region of STK35 and accelerate its
      transcription in response to hydrogen peroxide exposure. Furthermore,
      constitutive overexpression of STK35 proteins enhances caspase-independent cell
      death under oxidative stress conditions. These results collectively reveal that
      nuclear-localized importin alpha2 influences gene expression and contributes
      directly to cell fate outcomes including non-apoptotic cell death.

PMID- 21964069
TI  - A widespread family of bacterial cell wall assembly proteins.
AB  - Teichoic acids and acidic capsular polysaccharides are major anionic cell wall
      polymers (APs) in many bacteria, with various critical cell functions, including
      maintenance of cell shape and structural integrity, charge and cation
      homeostasis, and multiple aspects of pathogenesis. We have identified the
      widespread LytR-Cps2A-Psr (LCP) protein family, of previously unknown function,
      as novel enzymes required for AP synthesis. Structural and biochemical analysis
      of several LCP proteins suggest that they carry out the final step of
      transferring APs from their lipid-linked precursor to cell wall peptidoglycan
      (PG). In Bacillus subtilis, LCP proteins are found in association with the MreB
      cytoskeleton, suggesting that MreB proteins coordinate the insertion of the major
      polymers, PG and AP, into the cell wall.

PMID- 21964070
TI  - miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular
      antisense RNA.
AB  - MicroRNAs (miRNAs) are ~22 nt non-coding RNAs that typically bind to the 3' UTR
      of target mRNAs in the cytoplasm, resulting in mRNA destabilization and
      translational repression. Here, we report that miRNAs can also regulate gene
      expression by targeting non-coding antisense transcripts in human cells.
      Specifically, we show that miR-671 directs cleavage of a circular antisense
      transcript of the Cerebellar Degeneration-Related protein 1 (CDR1) locus in an
      Ago2-slicer-dependent manner. The resulting downregulation of circular antisense
      has a concomitant decrease in CDR1 mRNA levels, independently of heterochromatin
      formation. This study provides the first evidence for non-coding antisense
      transcripts as functional miRNA targets, and a novel regulatory mechanism
      involving a positive correlation between mRNA and antisense circular RNA levels.

PMID- 21964071
TI  - Limited availability of ZBP1 restricts axonal mRNA localization and nerve
      regeneration capacity.
AB  - Subcellular localization of mRNAs is regulated by RNA-protein interactions. Here,
      we show that introduction of a reporter mRNA with the 3'UTR of beta-actin mRNA
      competes with endogenous mRNAs for binding to ZBP1 in adult sensory neurons. ZBP1
      is needed for axonal localization of beta-actin mRNA, and introducing GFP with
      the 3'UTR of beta-actin mRNA depletes axons of endogenous beta-actin and GAP-43
      mRNAs and attenuates both in vitro and in vivo regrowth of severed axons.
      Consistent with limited levels of ZBP1 protein in adult neurons, mice
      heterozygous for the ZBP1 gene are haploinsufficient for axonal transport of beta
      actin and GAP-43 mRNAs and for regeneration of peripheral nerve. Exogenous ZBP1
      can rescue the RNA transport deficits, but the axonal growth deficit is only
      rescued if the transported mRNAs are locally translated. These data support a
      direct role for ZBP1 in transport and translation of mRNA cargos in axonal
      regeneration in vitro and in vivo.

PMID- 21964072
TI  - Insulin modulates ischemia-induced endothelial progenitor cell mobilization and
      neovascularization in diabetic mice.
AB  - Decreased levels of circulating endothelial progenitor cells (EPCs) predict
      increased risk of cardiovascular events in diabetic patients. Insulin treatment
      exerts important cardiovascular protection. Whether and how insulin participates
      in the EPC regulation of postnatal neovascularization are currently unclear. We
      employed a mouse hindlimb ischemia model to study EPC mobilization in non
      diabetic and streptozotocin-induced diabetic mice. Insulin was administered to
      diabetic animals postoperatively. To determine the role of EPCs contributing to
      postnatal vasculogenesis, we used bone marrow-transplanted mice whose bone marrow
      cells selectively expressed enhanced green fluorescent protein (EGFP). Insulin
      treatment improved EPC mobilization into peripheral blood, accelerated
      transcutaneous oxygen pressure restoration and increased capillary density in the
      ischemic limb associated with partial incorporation of EGFP-positive cells into
      the capillaries. Insulin treatment restored ischemia-induced release of stromal
      derived growth factor 1alpha and vascular endothelial growth factor (VEGF), and
      consequently enhanced the activity of Akt and endothelial nitric oxide synthase
      (eNOS) as well as matrix metalloproteinase-9 in bone marrow. Insulin also
      augmented tissue-level activation of VEGF/Akt/eNOS pathway. However, all such
      effects of insulin were completely blocked by combined treatment with a NOS
      inhibitor. Our data suggested that insulin treatment improved ischemia-induced
      EPC mobilization and contributed to compensatory neovascularization in diabetic
      mice through a VEGF/eNOS-related pathway.

PMID- 21964074
TI  - Charge state switching of deep levels for low-power optical modulation in silicon
      waveguides.
AB  - We demonstrate a method for the efficient modulation of optical wavelengths
      around 1550 nm in silicon waveguides. The amplitude of a propagating signal is
      mediated via control of the charge state of indium centers, rather than using
      free-carriers alone as in the plasma-dispersion effect. A 1*1 switch formed of an
      integrated p-i-n junction in an indium-doped silicon on insulator (SOI) waveguide
      provides 'normally-off' silicon absorption of greater than 7 dB at zero bias.
      This loss is decreased to 2.8 dB with application of a 6 V applied reverse bias,
      with a power consumption of less than 1 MUW.

PMID- 21964073
TI  - Akt2 knockout mitigates chronic iNOS inhibition-induced cardiomyocyte atrophy and
      contractile dysfunction despite persistent insulin resistance.
AB  - Increased levels of inducible nitric oxide synthase (iNOS) during cardiac stress
      such as ischemia-reperfusion, sepsis and hypertension may display both beneficial
      and detrimental roles in cardiac contractile performance. However, the precise
      role of iNOS in the maintenance of cardiac contractile function remains elusive.
      This study was designed to determine the impact of chronic iNOS inhibition on
      cardiac contractile function and the underlying mechanism involved with a special
      focus on the NO downstream signaling molecule Akt. Male C57 or Akt2 knockout
      [Akt2(-/-)] mice were injected with the specific iNOS inhibitor 1400W (2 mg/kg/d)
      or saline for 7 days. Both 1400W and Akt2 knockout dampened glucose and insulin
      tolerance without additive effects. Treatment of 1400W decreased heart and liver
      weights as well as cardiomyocyte cross-sectional area in C57 but not Akt2
      knockout mice. 1400W but not Akt2 knockout compromised cardiomyocyte mechanical
      properties including decreased peak shortening and maximal velocity of
      shortening/relengthening, prolonged relengthening duration, reduced intracellular
      Ca(2+) release and decay rate, the effects of which were ablated or attenuated by
      Akt2 knockout. Akt2 knockout but not 1400W increased the levels of intracellular
      Ca(2+) regulatory proteins including SERCA2a and phospholamban phosphorylation.
      1400W reduced the level of anti-apoptotic protein Bcl-2, the effect of which was
      unaffected by Akt2 knockout. Neither 1400W nor Akt2 knockout significantly
      affected ER stress, autophagy, the post-insulin receptor signaling Akt, GSK3beta
      and AMPK, as well as the stress signaling IkappaB, JNK, ERK and p38 with the
      exception of elevated IkappaB phosphorylation with jointed effect of 1400W and
      Akt2 knockout. Taken together, these data indicated that an essential role of
      iNOS in the maintenance of cardiac morphology and function possibly through an
      Akt2-dependent mechanism.

PMID- 21964075
TI  - Cavity stabilization using the weak intrinsic birefringence of dielectric
      mirrors.
AB  - We demonstrate a universal cavity stabilization scheme that exploits the
      intrinsic birefringence of dielectric multilayer mirrors. Homodyne locking using
      weak mirror birefringence of even an empty Fabry-Perot-type cavity requires
      neither frequency modulation nor mixing and allows us to generate an error signal
      that is comparable to more widely used heterodyne stabilization schemes.

PMID- 21964076
TI  - Toward whole-body optical imaging of rats using single-photon counting
      fluorescence tomography.
AB  - We used single-photon counting (SPC) detection for diffuse fluorescence
      tomography to image nanomolar (nM) concentrations of reporter dyes through a rat.
      Detailed phantom data are presented to show that every centimeter increase in
      tissue thickness leads to 1 order of magnitude decrease in the minimum
      fluorophore concentration detectable for a given detector sensitivity.
      Specifically, here, detection of Alexa Fluor 647 dyes is shown to be achievable
      for concentrations as low as 1 nM (<200 fM) through more than 5 cm in tissue
      phantoms, which indicates that this is feasible in larger rodent models. Because
      it is possible to detect sub-nM fluorescent inclusions with SPC technology in
      rats, it follows that it is possible to localize subpicomolar fluorophore
      concentrations in mice, putting the concentration sensitivity limits on the same
      order as nuclear medicine methods.

PMID- 21964077
TI  - Generation of intense sub-20-fs vacuum ultraviolet pulses compressed by material
      dispersion.
AB  - We present our latest results on the generation of ultrashort vacuum UV (VUV)
      pulses by nonresonant four-wave mixing of chirped broadband pulses generated by
      filamentation of the fundamental of a Ti:sapphire laser with relatively
      narrowband pulses at the third harmonic. Positive chirp at the broadband idler
      yields negatively chirped VUV pulses necessary to compensate for material
      dispersion of a MgF(2) window in the VUV beam path. Pulse energies exceeding 400
      nJ are available for time-resolved experiments. Pulse duration is measured by
      pump-probe ionization of Xe gas, providing the cross correlation between the
      fifth harmonic and the fundamental.

PMID- 21964078
TI  - Low-loss silica-on-silicon waveguides.
AB  - Waveguiding structures are one of the fundamental components of integrated
      photonic circuitry. Devices with low loss and a linear response across a wide
      wavelength range are especially desirable. In the present Letter, we have
      successfully developed and characterized low-loss silica waveguides integrated on
      a silicon substrate with a novel suspended cylinder geometry. The unique design
      creates a device that is effectively air clad, resulting in a large refractive
      index contrast for improved optical field confinement. The measured loss is
      constant from 658 to 1550 nm, and it is independent of the polarization of the
      input light and the input power.

PMID- 21964079
TI  - Product of three Airy beams.
AB  - A two-dimensional field that is a product of three Airy beams is proposed and
      investigated. It is shown that the Fourier image of this field has a cubic phase
      and a radially symmetric intensity with a super-Gaussian decrease. Propagation of
      the product of three Airy beams in a Fresnel zone is investigated numerically.

PMID- 21964080
TI  - Optical dynamics of energy-transfer from a CdZnO quantum well to a proximal Ag
      nanostructure.
AB  - We studied photoluminescence (PL) and energy-transfer dynamics in a hybrid
      structure comprising a Cd(0.08)Zn(0.92)O quantum well (QW) and an Ag
      nanostructure. The observed PL quenching was dependent on the electronic states
      in the QW. Quenching occurred at low temperature where excited carriers
      recombined radiatively because of excitonic localization, which disappeared with
      increasing temperature due to delocalization of excitons. Furthermore,
      nanostructured Ag surfaces produced local surface plasmon (LSP) absorption that
      was resonant with the PL peak energy of the QW emission. These results indicate
      that the recombination energy of excitons transfers nonradiatively to induce LSP
      excitation, which was revealed using time-resolved PL measurements.

PMID- 21964081
TI  - Application of complex-lag distributions for estimation of arbitrary order phase
      derivatives in digital holographic interferometry.
AB  - This Letter proposes a method to estimate phase derivatives of arbitrary order in
      digital holographic interferometry. Based on the desired order, the generalized
      complex-lag distribution is computed from the reconstructed interference field.
      Subsequently, the phase derivative is estimated by tracing the peak of the
      distribution. Simulation and experimental results are presented to validate the
      method's potential.

PMID- 21964082
TI  - Precise measurement of group refractive indices and temperature dependence of
      refractive index for Nd-doped yttrium orthovanadate by intracavity spontaneous
      mode locking.
AB  - We report on a novel method based on intracavity spontaneous mode locking to
      precisely measure the group refractive indices and temperature dependence of
      refractive index of Nd:YVO(4) crystal at the wavelength of 1064 nm. All the
      experimental results are found to agree very well with the most recent measured
      values. We also confirm that the developed method is applicable to measuring the
      group refractive indices and the temperature dependence of the refractive indices
      of other vanadate crystals, as well as nonlinear crystals.

PMID- 21964083
TI  - Broadly wavelength tunable bandpass filters based on long-range surface plasmon
      polaritons.
AB  - We report a new kind of broadly tunable optical bandpass filters based on unusual
      properties of long-range surface plasmon polaritons. A 0.004 variation in the
      refractive index of the dielectric medium translates into 210 nm of bandpass
      tuning at telecom wavelengths. The tuning mechanism reported here may be used to
      create compact and widely tunable optical systems and other plasmonic components
      with broadly tunable optical response.

PMID- 21964084
TI  - Tunable wavelength division multiplexing channel isolation filter based on dual
      chirped long-period fiber gratings.
AB  - We propose and demonstrate a wavelength tunable wavelength division multiplexing
      channel isolation filter based on two concatenated chirped long-period fiber
      gratings (LPGs). An intergrating space (IGS), deliberately introduced between the
      two gratings, provides an extra phase difference between the core and cladding
      modes. Changing this phase by heating the IGS without affecting the gratings
      tunes the channels. A theoretical account of the filter action is also presented
      and the results are found to be in excellent agreement with the experiments.
      Unlike the filters based on normal concatenated chirped LPGs without an IGS, the
      current filter shows a linear tuning over an increased spectral range.

PMID- 21964085
TI  - All-fiber passively mode-locked thulium-doped fiber ring oscillator operated at
      solitary and noiselike modes.
AB  - This Letter presents an all-fiber mode-locked thulium-doped fiber ring oscillator
      based on nonlinear polarization evolution (NPE). Pumped by an erbium-doped fiber
      amplified spontaneous emission source, the construction of the laser cavity
      consisting of only fiber optic components can operate under two different regimes
      of solitary and noiselike (NL) pulses. Autocorrelation measurements are performed
      to extract features of these two regimes.

PMID- 21964086
TI  - Fiber Mach-Zehnder interferometer based on microcavities for high-temperature
      sensing with high sensitivity.
AB  - A high-temperature sensor based on a Mach-Zehnder interferometer (MZI) in a
      conventional single-mode optical fiber is proposed and fabricated by
      concatenating two microcavities separated by a middle section. A femtosecond
      laser is used to fabricate a microhole on the center of a fiber end. Then a micro
      air-cavity is formed by splicing the microholed fiber end with a normal fiber
      end. The interferometer is applied for high-temperature sensing, in the range of
      500-1200  degrees C, with a sensitivity of 109 pm/ degrees C that, to the best of
      our knowledge, is highest in silica fiber temperature sensors. Also, the
      interferometer is insensitive to external refractive index (RI), which is
      desirable for temperature sensors.

PMID- 21964087
TI  - Compact interrogator for fiber optic Bragg sensors based on an acousto-optic
      filter formed by photonic crystal rows of air holes.
AB  - Fiber optic sensors are typically used with expensive tunable lasers or optical
      spectrum analyzers for wavelength interrogation. We propose to replace the
      tunable laser by a broadband optical source incorporated with a novel thin
      linewidth acousto-optic tunable filter. It utilizes optical beam expanders
      constituted by photonic crystal rows of air holes in LiNbO(3) waveguide. A new
      design is numerically studied for a short structure (with 32 photonic crystal
      rows) by a two-dimensional finite-difference time-domain method. Extrapolation of
      these results to larger structure sizes (about 1 cm) demonstrates the possibility
      to develop compact interrogators with 0.4 pm wavelength resolution and 40 nm
      tunable range around 1550 nm.

PMID- 21964088
TI  - Subpicometer length measurement using semiconductor laser tracking frequency
      gauge.
AB  - We have demonstrated heretofore unattained distance precision of 0.14 pm (2 pm)
      incremental and 14 nm (2.9 MUm) absolute in a resonant (nonresonant)
      interferometer at an averaging time of 1 s, using inexpensive telecommunications
      diode lasers. We have controlled the main source of error, that due to spurious
      reflection and the resulting amplitude modulation. In the resonant
      interferometer, absolute distance precision is well under lambda/6. Therefore,
      after an interruption, an absolute distance measurement can be used to return to
      the same interferometer order.

PMID- 21964089
TI  - Nonlinear diffraction in photonic graphene.
AB  - The nonlinear (NL) diffraction of wave packets in honeycomb lattices near Dirac
      points is studied. Strong nonlinearity can significantly deform the diffraction
      patterns from conical to triangular structure. This is described by a mean field
      discrete NL Dirac system and in the continuous limit by a higher-order NL Dirac
      system, which, in turn, is consistent with the trigonal warping of the dispersion
      relation. The anticontinuous limit is also examined and similar properties are
      obtained.

PMID- 21964090
TI  - Fermionic out-of-plane structure of polarization singularities.
AB  - A new classification of circular polarization C points in three-dimensional
      polarization ellipse fields is proposed. The classification type depends on the
      out-of-plane variation of the polarization ellipse axis, in particular, whether
      the ellipse axes are in the plane of circular polarization one or three times. A
      minimal set of parameters for this classification is derived and discussed in the
      context of the familiar in-plane C point classification into lemon, star, and
      monstar types. This new geometric classification is related to the Mobius index
      of polarization singularities recently introduced by Freund.

PMID- 21964091
TI  - Sufficient condition for polarization invariance of beams generated by quasi
      homogeneous sources.
AB  - Conditions for invariance of the degree and the state of polarization of beams
      radiated by electromagnetic quasi-homogeneous sources into the far-zone are
      derived. An example is given relating to electromagnetic Bessel-correlated
      sources.

PMID- 21964092
TI  - All-fiber wavelength-swept laser near 2 MUm.
AB  - We report, for the first time to our knowledge, an all-fiber wavelength-swept Tm
      doped laser based on a fiber Fabry-Perot tunable filter in the 2 MUm spectral
      region. The laser wavelength can be continuously tuned over 200 nm from 1840 to
      2040 nm in a short period of time. The demonstrated tuning speed was 12.5 MUm/s
      with a tuning efficiency of 17.5 nm/V. The spectral linewidth of the laser was
      measured to be approximately 300 MHz or 0.01 cm(-1). This kind of laser can find
      potential applications in both high-resolution laser spectroscopy and tunable mid
      IR generation via nonlinear frequency conversion.

PMID- 21964093
TI  - Exact analytical representations for broadband transmission properties of quarter
      wave multilayers.
AB  - The formalism of the scattering matrix is applied to describe the transmission
      properties of multilayered structures with deep variations of the refractive
      index and arbitrary arrangements of the layers. We show that there is an exact
      analytical formula for the transmission spectrum, which is valid for the full
      spectral range and which contains only a limited number of parameters for
      structures satisfying the quarter-wave condition. These parameters are related to
      the poles of the scattering matrix, and we present an efficient algorithm to find
      them, which is based on considering the ray propagation inside the structure and
      subsequent application of the harmonic inversion technique. These results are
      significant for analyzing the reshaping of ultrashort pulses in multilayered
      structures.

PMID- 21964094
TI  - Tailoring wave chaos in vertical-cavity surface-emitting lasers via polarization
      control.
AB  - We demonstrate that polarization control in combination with the geometrical
      shape affects wave chaos phenomena in vertical-cavity surface-emitting lasers
      (VCSELs). In a grating-polarization-stabilized VCSEL, we demonstrate wave chaos
      in one polarization mode and a transition from wave chaos to regular behavior in
      the other orthogonal polarization mode. We quantify the amount of chaoticity via
      the Brody nearest-neighbor distribution. Comparing with a reference VCSEL without
      a surface-grating, we explain these results and their injection current
      dependence by the surface-grating-induced mode selection and a change in the
      effective resonator shape.

PMID- 21964095
TI  - Time-domain near-infrared spectroscopy using a wavelength-tunable narrow
      linewidth source by spectral compression of ultrashort soliton pulses.
AB  - Time-domain absorption spectroscopy was demonstrated using a wideband, rapid
      wavelength-tunable, narrow-linewidth source based on an Er-doped ultrashort pulse
      fiber laser system. The spectrum of the Raman-shifted ultrashort soliton pulse
      was compressed using a comb-profile dispersion increasing fiber. Rapid wavelength
      sweeping was demonstrated using an electro-optical intensity modulator. The
      absorption spectrum of CH(2)Cl(2) liquid at 1625-1780 nm was observed in a 10 MUs
      time-domain measurement.

PMID- 21964096
TI  - Vortex twins and anti-twins supported by multiring gain landscapes.
AB  - We address the properties of multivortex soliton complexes supported by multiring
      gain landscapes in focusing Kerr nonlinear media with strong two-photon
      absorption. Stable complexes incorporating two, three, or four vortices featuring
      opposite or identical topological charges are shown to exist. In the simplest
      geometries with two amplifying rings vortex twins with equal topological charges
      exhibit asymmetric intensity distributions, while vortex anti-twins may be
      symmetric or asymmetric, depending on the gain level and separation between
      rings.

PMID- 21964098
TI  - Elastomeric microwire-based optical gas flowmeter with stretching-enabled
      tunability in measurement range.
AB  - We report the utilization of transparent poly(dimethylsiloxane) (PDMS) microwires
      as the transducer for optical gas flowmetry. The elasticity of the PDMS microwire
      was exploited not only to miniaturize and simplify the flowmeter but also to
      widen and tune the measurement range through mechanical stretching. Using a 9 mm
      long microwire, we achieved 2.8~9.8 dB/SLM sensitivity. A 500 MUm stretching of
      the microwire also shifted the measurement range from 1 to 4 SLM. The
      experimental results agreed well with predictions based on the fluid
      dynamic/optical model.

PMID- 21964097
TI  - Lucky averaging: quality improvement of adaptive optics scanning laser
      ophthalmoscope images.
AB  - Adaptive optics (AO) has greatly improved retinal image resolution. However, even
      with AO, temporal and spatial variations in image quality still occur due to
      wavefront fluctuations, intraframe focus shifts, and other factors. As a result,
      aligning and averaging images can produce a mean image that has lower resolution
      or contrast than the best images within a sequence. To address this, we propose
      an image postprocessing scheme called "lucky averaging," analogous to lucky
      imaging [J. Opt. Soc. Am. 68, 1651 (1978)] based on computing the best local
      contrast over time. Results from eye data demonstrate improvements in image
      quality.

PMID- 21964099
TI  - Picosecond bismuth-doped fiber MOPFA for frequency conversion.
AB  - We report the development of a bismuth-doped fiber master oscillator power fiber
      amplifier system. The system operates at 1177 nm, producing 28 ps pulses at 9.11
      MHz repetition rate, with an output power of 150 mW and a peak pulse power of 580
      W. We subsequently frequency double the output, resulting in a picosecond pulsed
      visible source operating at 588.5 nm, with a maximum average output power of 13.7
      mW.

PMID- 21964100
TI  - Demonstration of a directed optical encoder using microring-resonator-based
      optical switches.
AB  - We propose and demonstrate a directed optical logic circuit that performs the
      encoding function from a 4 bit electrical signal to a 2 bit optical signal based
      on cascaded microring switches. The four logic input signals control the states
      of the switches, while the two logic outputs are given by the optical power at
      the output waveguides. For proof of concept, a thermo-optic switching effect is
      used with an operation speed of 10 kbps.

PMID- 21964101
TI  - Fringe localization using focus measure.
AB  - A method for automated evaluation of fringe localization using focus measure is
      demonstrated experimentally. Dual-illumination digital holographic interferometry
      is used to generate phase difference maps (PDMs) of a rough test object. Focus
      measure values of the PDMs along the axial direction (increment: 10lambda=6.33
      MUm) yield an inverted bell-shaped curve which, in turn, facilitates the
      characterizations of the plane and region of fringe localization. The method can
      be applied in the distance measurement of rough objects and in the optimization
      of fringe visibility.

PMID- 21964102
TI  - Surface dark screening solitons.
AB  - We report on the existence of surface dark screening solitons at the interface
      between a dielectric medium (air) and a self-defocusing nonlinear material,
      taking advantage of photorefractive diffusion and drift nonlinearities. It is
      very interesting that a surface dark soliton is just like half of a dark soliton
      in bulk, but not a whole dark soliton propagating along surface. The excitation,
      propagation, and stability of this type of soliton are studied by using the beam
      propagation method. Another interesting thing is that this type of dark soliton
      can be excited by a planar light beam without a necessary dark notch.

PMID- 21964103
TI  - Time-stretch oscilloscope with dual-channel differential detection front end for
      monitoring of 100 Gb/s return-to-zero differential quadrature phase-shift keying
      data.
AB  - Optical performance monitoring of high-capacity networks is one of the enabling
      technologies of future reconfigurable optical switch networks. In such networks,
      rapid performance evaluation of data streams becomes challenging due to the use
      of advanced modulation formats and high data rates. The time-stretch enhanced
      recording oscilloscope offers a potential solution to monitoring high-rate data
      in a practical time scale. Here we demonstrate an architecture with a
      differential detection front end for simultaneous I/Q data monitoring of a 100
      gigabits/s return-to-zero differential quadrature phase-shift keying signal. This
      demonstration shows the potential of this technology for rapid performance
      monitoring of high-rate optical data streams that employ advanced modulation
      formats.

PMID- 21964104
TI  - Scanning monochromatic spatial low-coherence interferometer.
AB  - A scanning spatial low-coherence interferometer (S-LCI), using an off-axis
      converging single wavelength laser beam as the probe, resembles a conventional or
      temporal low-coherence interferometer (T-LCI) in signal formation and data
      processing. However, the S-LCI is advantageous over a T-LCI with the combination
      of angle resolving and depth discrimination capabilities. The S-LCI is
      demonstrated by measuring the angle dependent phase shifts among the multiple
      reflections of a glass plate, with incident angles accurately scaled in the
      Fourier domain. The refractive index and geometric thickness of the glass plate
      are simultaneously produced in this one-step measurement.

PMID- 21964105
TI  - Passive coherent beam combining of quantum-cascade lasers with a Dammann grating.
AB  - An external cavity using a binary phase grating has been developed to achieve
      coherent combining of five quantum-cascade lasers emitting at 4.65 MUm. The
      grating phase profile is designed to combine five beams of equal intensities into
      a single beam with a good efficiency (~75%). The performances of this cavity
      concerning output power, stability, combining efficiency and beam quality are
      detailed. We report a CW combining efficiency of 66% corresponding to an output
      power of ~0.5 W with a good beam quality (M(2)<1.6).

PMID- 21964106
TI  - Efficient diode-end-pumped dual-wavelength Nd, Gd:YSGG laser.
AB  - We demonstrate a dual-wavelength laser based on a new laser material-Nd, Gd:YSGG,
      or Nd:GYSGG for short-for the first time to our knowledge. Besides its attractive
      properties such as antiradiation, high segregation coefficient, etc., this kind
      of laser crystal also shows excellent laser performance. For continuous-wave
      operation, the maximum output power is 10.1 W with the absorbed power of 18.45 W
      at 808 nm, corresponding to the slope efficiency of nearly 60%. The maximum
      single pulse energy and peak power reach 277 MUJ and 4.6 kW (60 ns) when the
      absorbed pump power is 11.4 W for acousto-optic Q-switched operation.

PMID- 21964107
TI  - Broadband high-energy diode-pumped Yb:KYW multipass amplifier.
AB  - We report a diode-pumped Yb:KYW amplifier delivering up to 27 mJ pulses at a
      repetition rate of 100 Hz and a spectral bandwidth of 5.5 nm, centered at around
      1030 nm. The system is based on a double-head multipass amplifier configuration
      where the pump thermal load is distributed over two relatively thin laser
      crystals, which permits a sufficiently large number of passes with minimal
      passive losses, thus maximizing the energy extraction efficiency. The amplified
      pulse bandwidth theoretically supports 340 fs pulses, and as a demonstration, a
      small fraction of the amplified pulses has been compressed to 560 fs.

PMID- 21964108
TI  - Mode-locked 0.5 MUJ fiber laser at 976 nm.
AB  - We report on high-energy femtosecond pulse generation from an ytterbium-doped rod
      type fiber oscillator emitting around 976 nm. Self-starting and stable single
      pulse operation are demonstrated with 4.2 W of average output power at a
      repetition rate of 8.4 MHz. The resulting energy level reaches 0.5 MUJ. Because
      of the all-normal dispersion of the laser cavity, output pulses are naturally
      chirped with a duration of 14 ps. External compression using diffraction gratings
      shortens the pulse duration down to 460 fs.

PMID- 21964109
TI  - Effect of a plasma grating on pump-probe experiments near the ionization
      threshold in gases.
AB  - Calculations are performed of the phase shift caused by the spatial modulation in
      the plasma density due to interference between a strong pump pulse and a weak
      probe pulse. It is suggested that a recent experiment [Opt. Express 17, 13429
      (2009)] observed an effective birefringence from this plasma grating rather than
      from the higher-order Kerr effect.

PMID- 21964110
TI  - Thermo-optical switching enhanced with second harmonic generation in microring
      resonators.
AB  - We investigate the thermo-optic effects on second harmonic generation (SHG) in
      AlGaAs/AlO(x) microring (MR) waveguides. We show that SHG can be utilized to
      enhance the thermal sensitivity of MRs. This sensitivity makes this structure
      appropriate for thermal modulation and switching of optical signals or
      temperature sensing.

PMID- 21964111
TI  - Photonic generation of triangular waveform signals by using a dual-parallel Mach
      Zehnder modulator.
AB  - A photonic approach to generate triangular waveform signals is proposed and
      analyzed. With active bias control, two sub-MZMs (MZ-a and MZ-b) of a dual
      parallel Mach-Zehnder modulator (DP-MZM) operate at minimum transmission point,
      leaving the main MZM (MZ-c) at quadrature transmission point. Triangular waveform
      can be observed by a parameter setting of modulation index. The proposal is first
      analyzed and then validated by simulation. The key significance of the scheme is
      that it is capable of generating triangular waveform signals via a sinusoid local
      oscillator.

PMID- 21964112
TI  - All-fiber polarization locked vector soliton laser using carbon nanotubes.
AB  - We report an all-fiber mode-locked erbium-doped fiber laser (EDFL) employing
      carbon nanotube (CNT) polymer composite film. By using only standard telecom
      grade components, without any complex polarization control elements in the laser
      cavity, we have demonstrated polarization locked vector solitons generation with
      duration of ~583 fs, average power of ~3 mW (pulse energy of 118 pJ) at the
      repetition rate of ~25.7 MHz.

PMID- 21964113
TI  - Self-focusing of femtosecond diffraction-resistant vortex beams in water.
AB  - We report experiments on self-focusing of femtosecond diffraction-resistant
      vortex beams in water. These beams are higher-order Bessel beams with weak
      azimuthal modulation of the transverse intensity patterns. The modulation
      overrides the self-focusing dynamics and results in the formation of regular
      bottlelike filament distributions. The peak-power thresholds for filamentation,
      at a particular distance, are relatively accurately estimated by the adaptation
      of the Marburger formula derived earlier for Gaussian beams. The nonlinear
      conversion of the incident conical waves into the localized spatial wave packets
      propagating near the beam axis is observed.

PMID- 21964114
TI  - Ultrafine optical-frequency tunable Brillouin fiber laser based on fiber strain.
AB  - We present an ultrafine tunable single-frequency Brillouin fiber laser in which
      the fiber Brillouin gain also acts as a high-precision tunable filter.
      Controlling the strain on the fiber, the Stokes frequency shift may be precisely
      changed, and thus the lasing frequency can be tuned. Assisted by the frequency
      pulling effect, this method provides continuous ultrafine tuning ability for ~30%
      of the free spectral range without mode hopping, and can cover 271 MHz. The
      experiments showed that the laser achieves tuning step of 60 kHz.

PMID- 21964115
TI  - Tuning of optical resonances in asymmetric microtube cavities.
AB  - We tune optical resonances in rolled-up SiO/SiO(2) microtube cavities by
      gradually modifying the tube structure through asymmetrical postdeposition of
      SiO(2). Spectral blueshifts followed by redshifts of the resonant modes are
      observed in a thin-walled microtube (tube-I), which is attributed to a
      competition between shape deformation and effective increase of tube wall
      thickness. In contrast, only a monotonic redshift is detected when asymmetrical
      deposition is performed on a thick-walled microtube (tube-II). Distinct
      wavelength-dependent tuning was revealed in both kinds of tubes. Numerical
      calculations based on perturbation theory are carried out to explain and confirm
      the experimental results.

PMID- 21964116
TI  - Adiabatic self-focusing in media with spatially variable nonlinearity.
AB  - An optical medium whose nonlinearity can be spatially adjusted is considered to
      study beam reshaping. The concept is applied to perform adiabatic self-focusing
      of broad beams. Experimental results are obtained in a photorefractive lithium
      niobate crystal where the self-focusing nonlinearity is controlled over
      propagation by a temperature gradient. As a demonstration, gradual self-focusing
      is shown to transform an incoming beam into an output circular spot 10 times
      smaller over a 2 cm long crystal submitted to a 30  degrees C temperature
      gradient. Once formed, the adiabatic self-focused beam has inscribed a funnel
      waveguide in the crystal.

PMID- 21964117
TI  - Scalable InP integrated wavelength selector based on binary search.
AB  - We present an InP monolithically integrated wavelength selector that implements a
      binary search for selecting one from N modulated wavelengths. The InP chip
      requires only log(2)N optical filters and log(2)N optical switches. Experimental
      results show nanosecond reconfiguration and error-free wavelength selection of
      four modulated wavelengths with 2 dB of power penalty.

PMID- 21964118
TI  - Three-dimensional nonlinear microspectroscopy and imaging of soft condensed
      matter.
AB  - We report on the realization of a sensitive microspectroscopy and imaging
      approach based on a three-color femtosecond coherent anti-Stokes Raman scattering
      (CARS) technique with high spectral, time, and spatial resolution. Independently
      tunable, high-repetition rate optical parametric oscillators were used to attain
      a dynamic range of 5 orders of magnitude for time-domain CARS signal. The
      attained sensitivity permitted tracing the decay of weak and structurally complex
      Raman active modes in soft condensed matter. Application of this approach to
      imaging of the biological specimen shows a great potential in quantitative
      characterization of live biological media with an ability to access inter- and
      intra-molecular interactions.

PMID- 21964119
TI  - Efficient high-power self-frequency-doubling Nd:GdCOB laser at 545 and 530 nm.
AB  - We report an efficient high-power self-frequency-doubling (SFD) Nd:GdCOB laser.
      The maximum output power is 3.01 W at a wavelength of 545 nm with an optical
      efficiency of 20.7%, which, to our knowledge, is the highest SFD laser output
      power and efficiency yet obtained. By optimizing the configuration and cut
      orientation of the Nd:GdCOB crystals, a SFD laser at a wavelength of about 530 nm
      was achieved with a maximum output power of 1.32 W. We propose that these SFD
      lasers will have promise in applications such as laser displays, medical
      treatment, spectroscopic analysis, etc.

PMID- 21964120
TI  - Waveguide devices with homogeneous complementary media.
AB  - We report the design of microwave waveguide devices based on complementary media.
      Various kinds of waveguide devices that possess nearly 100% transmission
      efficiency are proposed, such as waveguide bends, splitters, connectors, and
      shifters. Compared with previous work on waveguide devices of low reflection and
      minimized distortion based on transformation optics, our transform media are
      homogeneous metamaterials. Electromagnetic simulations by a finite-element method
      on detailed examples have been performed to validate the designs and these
      functionalities can be close to the practical.

PMID- 21964121
TI  - 88 W 0.5 mJ femtosecond laser pulses from two coherently combined fiber
      amplifiers.
AB  - The generation of 0.5 mJ femtosecond laser pulses by coherent combining of two
      high power high energy fiber chirped-pulse amplifiers is reported. The system is
      running at a repetition frequency of 175 kHz producing 88 W of average power
      after the compressor unit. Polarizing beam splitters have been used to realize an
      amplifying Mach-Zehnder interferometer, which has been stabilized with a Hansch
      Couillaud measurement system. The stabilized system possesses a measured residual
      rms phase difference fluctuation between the two branches as low as lambda/70 rad
      at the maximum power level. The experiment proves that coherent addition of
      femtosecond fiber lasers can be efficiently and reliably performed at high B
      integral and considerable thermal load in the individual amplifiers.

PMID- 21964122
TI  - Negative group velocity and three-wave mixing in dielectric crystals.
AB  - We investigate extraordinary features of optical parametric amplification of
      Stokes electromagnetic waves that originate from the three-wave mixing of a
      backward phonon wave with negative group velocity and two ordinary
      electromagnetic waves. Such properties were earlier shown to exist only in
      plasmonic negative-index metamaterials that are very challenging to fabricate.
      Nonlinear optical photonic devices with properties similar to those predicted for
      negative-index metamaterials are proposed.

PMID- 21964123
TI  - Optical switch of diffractive light from a BCT photonic crystal based on HPDLC
      doped with azo component.
AB  - This study demonstrates an optical switch of the diffractive light from a body
      centered tetragonal photonic crystal based on holographic polymer-dispersed
      liquid crystals that are fabricated using two-beam interference with multiple
      exposures. The liquid crystal-rich regions form the lattice points of the PC,
      which contains a liquid crystal/azo-dye mixture. The concentration of the cis
      isomer changes under laser light exposure; this change, in turn, modulates the
      effective index of the LCs, and then switches diffractive light.

PMID- 21964124
TI  - Enhancement of filamentation postcompression by astigmatic focusing.
AB  - The energy scaling up of pulse postcompression is still an open issue. In this
      work we analyze the use of astigmatic focusing to improve the output pulses in a
      filamentation based postcompression setup. Unlike spherical conditions,
      astigmatic focusing enhances the output energy and the spectral broadening of the
      filament. This is due to the increase of critical power, allowing a considerable
      improvement of the postcompression energy and stability in a simple way. We
      demonstrated compression from FWHM 100 fs, 10 nm, 3 mJ input pulses to 13 fs, 142
      nm, near 1 mJ pulses.

PMID- 21964125
TI  - Pump-soliton nonlinear wave mixing in noise-driven fiber supercontinuum
      generation.
AB  - We report on the experimental observation of nonlinear mixing between Raman
      shifting solitons and residual pump radiation in supercontinuum generation in the
      long-pulse regime. This resonant coherent process results in the generation of
      strong and isolated spectral components on the long-wavelength normal dispersion
      regime of a fiber with two zero-dispersion wavelengths. Our observations are in
      excellent agreement with numerical simulations and calculated phase-matching
      conditions.

PMID- 21964127
TI  - Wide tuning of silicon-on-insulator ring resonators with a liquid crystal
      cladding.
AB  - Wide electrical tuning of silicon-on-insulator ring resonators is demonstrated
      using a top cladding layer of nematic liquid crystals. A tuning range of 31 nm is
      demonstrated for ring resonators guiding the TM mode, covering nearly the entire
      C-band of optical communications. Ring resonators guiding the TE mode can be
      tuned over 4.5 nm. The combination of a liquid crystal director calculation and a
      fully anisotropic mode solver confirms the interpretation of these experimental
      results. The realization of broad and low-power tuning in silicon-on-insulator
      opens up new opportunities in the field of tunable lasers, filters, and
      detectors.

PMID- 21964126
TI  - Lasing in thulium-doped polarizing photonic crystal fiber.
AB  - We describe lasing of a thulium-doped polarizing photonic crystal fiber. A 4 m
      long fiber with 50 MUm diameter core, 250 MUm diameter cladding, and d/Lambda
      ratio of 0.18 was pumped with a 793 nm diode and produced a polarized output with
      a polarization extinction ratio (PER) of 15 dB and an M(2) of <1.15. An
      intracavity polarizer and half-wave plate minimally increased the PER to 16 dB.
      The output power had 35% slope efficiency relative to the absorbed pump power.
      The maximum cw output power was limited to 4 W due to the quantum defect heating
      of the fiber.

PMID- 21964128
TI  - Rapid fabrication of microhole array structured optical fibers.
AB  - A microhole array in a common single-mode fiber is fabricated by selective
      chemical etching of femtosecond-laser-induced fiber Bragg grating (FBG), which
      has a laser-modified region extending from the fiber core to the cladding-air
      boundary due to laser self-focusing. The shape and size of the orderly microhole
      on the fiber surface are controlled via changing conditions of FBG fabrication
      and chemical etching. A simultaneous sensing for surrounding refractive index and
      temperature is demonstrated by this microhole array FBG through measurement of
      the transmission power change and Bragg resonant wavelength shift.

PMID- 21964129
TI  - Fabrication of a mid-IR wire-grid polarizer by direct imprinting on chalcogenide
      glass.
AB  - A mid-IR wire-grid polarizer with a 500 nm pitch was fabricated on a low toxic
      chalcogenide glass (Sb-Ge-Sn-S system) by the thermal imprinting of periodic
      grating followed by the thermal evaporation of Al metal. After imprinting,
      deposition of Al on the grating at an oblique angle produced a wire-grid
      polarizer. The fabricated polarizer showed polarization with TM transmittance
      greater than 60% at 5-9 MUm wavelengths and an extinction ratio greater than 20
      dB at 3.5-11 MUm wavelengths. This polarizer with a high extinction ratio can be
      fabricated more simply and less expensively than conventional IR polarizers.

PMID- 21964130
TI  - Group and phase velocity coupling of colliding pulses in a nanostructure.
AB  - It is generally accepted that, in a laser cavity, the group delay--responsible
      for the round trip time--and the phase delay both have a linear dependence on the
      cavity length. We show that nanostructures, such as quantum wells, can create a
      coupling between phase and group velocities, resulting in a periodic dependence
      of the repetition rate on the laser cavity length.

PMID- 21964131
TI  - Diode-pumped femtosecond Yb:CaNb2O6 laser.
AB  - We report to our knowledge a diode-pumped passively mode-locked Yb:CaNb(2)O(6)
      (Yb:CN) laser for the first time. Both CW and passive mode-locking operation of
      the laser are experimentally investigated. A maximum CW output power of 1.4 W
      with a slope efficiency of 20% is obtained on a 7 mm long 1.5 at.% Yb:CN crystal,
      while stable passive mode-locking with a commercial semiconductor saturable
      absorption mirror (SESAM) was achieved on a 3 mm long 3 at.% Yb:CN crystal. The
      mode-locked pulses have pulse width of 251 fs and an average output power of 44
      mW at 1038 nm.

PMID- 21964132
TI  - Rapid vibrational imaging with sum frequency generation microscopy.
AB  - We demonstrate rapid vibrational imaging based on sum frequency generation (SFG)
      microscopy with a collinear excitation geometry. Using the tunable picosecond
      pulses from a high-repetition-rate optical parametric oscillator, vibrationally
      selective imaging of collagen fibers is achieved with submicrometer lateral
      resolution. We furthermore show simultaneous SFG and second harmonic generation
      imaging to emphasize the compatibility of the microscope with other nonlinear
      optical modalities.

PMID- 21964133
TI  - Ultrathin side-viewing needle probe for optical coherence tomography.
AB  - We present the smallest reported side-viewing needle probe for optical coherence
      tomography (OCT). Design, fabrication, optical characterization, and initial
      application of a 30-gauge (outer diameter 0.31 mm) needle probe are demonstrated.
      Extreme miniaturization is achieved by using a simple all-fiber probe design
      incorporating an angle-polished and reflection-coated fiber-tip beam deflector.
      When inserted into biological tissue, aqueous interstitial fluids reduce the
      probe's inherent astigmatism ratio to 1.8, resulting in a working distance of 300
      MUm and a depth-of-field of 550 MUm with beam diameters below 30 MUm. The needle
      probe was interfaced with an 840 nm spectral-domain OCT system and the measured
      sensitivity was shown to be only 7 dB lower than that of a comparable galvo
      scanning sample arm configuration. 3D OCT images of lamb lungs were acquired over
      a depth range of ~600 MUm, showing individual alveoli and bronchioles.

PMID- 21964134
TI  - Photonic approach for microwave spectral analysis based on Fourier cosine
      transform.
AB  - A photonic approach for microwave spectral analysis based on Fourier cosine
      transform is proposed. The spectral information is obtained by processing a
      microwave power versus dispersion function, which is the product of the power
      spectrum of the signal with its spectrum to be analyzed and the power transfer
      function of the phase-modulated radio over dispersive link system. We demonstrate
      that the approach is capable of analyzing microwave signals with multiple
      frequency components. The sensitivity, the spectral resolution, and the effective
      measurement bandwidth of the scheme are quantitatively discussed.

PMID- 21964135
TI  - Broadband supercontinuum generation in air using tightly focused femtosecond
      laser pulses.
AB  - Supercontinuum generation in air using tightly focused femtosecond laser pulses
      was investigated experimentally. Broadband white-light emission covering the
      whole visible spectral region was generated. Spectral broadening extended only to
      the blue side of the fundamental frequency due to the phase modulation induced by
      the strong ionization of air. Numerical simulation was also performed to confirm
      the spectral broadening mechanism. A constant UV cutoff wavelength close to 400
      nm was observed in the supercontinuum spectrum. This phenomenon indicated that
      intensity clamping still plays a role in tight focusing geometry.

PMID- 21964136
TI  - Intrachannel nonlinearity enhancement in polarization multiplexed phase modulated
      systems with differential detection.
AB  - We compare nonlinear impairments in phase-modulated transmission with and without
      polarization multiplexing. Using an analytic approach that enabled us to
      accurately predict the Q factor at the receiver, we show that, without
      polarization multiplexing, the differential receiver is insensitive to two-pulse
      cross phase modulation, whereas with polarization multiplexing two-pulse
      interaction between cross-polarized components causes significant performance
      degradation.

PMID- 21964137
TI  - Generation of spirally polarized propagation-invariant beam using fiber
      microaxicon.
AB  - We present here a fiber microaxicon (MA)based method to generate spirally
      polarized propagation-invariant optical beam. MA chemically etched in the tip of
      a two-mode fiber efficiently converts the generic cylindrically polarized vortex
      fiber mode into a spirally polarized propagation-invariant (Bessel-type) beam via
      radial dependence of polarization rotation angle. The combined roles of helico
      conical phase and nonparaxial propagation in the generation and characteristics
      of the output beam from the fiber MA are discussed.

PMID- 21964138
TI  - Generation of 520 mW pulsed blue light by frequency doubling of an all-fiberized
      978 nm Yb-doped fiber laser source.
AB  - Pulsed blue light at 489 nm has been generated by second-harmonic-generation of a
      nanosecond pulsed master-oscillator power amplifier system based on a short
      Yb(3+) doped single-mode fiber amplifier at 978 nm and an external-cavity diode
      laser as seed source. The Yb(3+)-doped fiber was core-pumped by a W type Nd(3+)
      doped double-clad fiber laser operating on the transition near 930 nm ((4)F(3/2)
      >(4)I(9/2)). 520 mW of average power was generated at 489 nm using a periodically
      poled MgO:LiNbO(3), corresponding to a conversion efficiency of 34%.

PMID- 21964139
TI  - Supercontinuum generation in quasi-phase-matched LiNbO3 waveguide pumped by a Tm
      doped fiber laser system.
AB  - We demonstrate self-referencing of a Tm-doped fiber oscillator-amplifier system
      by performing octave-spanning supercontinuum generation in a periodically poled
      lithium niobate waveguide. We model the supercontinuum generation numerically and
      show good agreement with the experiment.

PMID- 21964140
TI  - Grating amplitude effect on electroluminescence enhancement of corrugated organic
      light-emitting devices.
AB  - We report grating amplitude dependence of electroluminescence (EL) in organic
      light-emitting devices with one-dimensional corrugated structure. Our proposed
      devices can emit light from both the top silver and bottom quartz side, and both
      exhibit amplitude-dependence EL enhancement. The effect of grating amplitude on
      the EL intensity has been studied experimentally and numerically to find out the
      optimal grating amplitude for the greatest EL enhancement. We deduce from the
      numerical simulations and experimental results that surface plasmon-polariton
      modes and waveguide modes are coupled out of the corrugated devices efficiently
      at the optimal amplitude; therefore, higher efficiency of light extraction could
      be realized.

PMID- 21964141
TI  - Sub-250-mrad, passively carrier-envelope-phase-stable mid-infrared OPCPA source
      at high repetition rate.
AB  - An all-optical and passively carrier-to-envelope-phase-stabilized (CEP
      stabilized) optical parametric chirped pulse amplification (OPCPA) system is
      demonstrated with sub-250-mrad CEP stability over 11 min and better than 100 mrad
      over 11 s. This is achieved without any electronic CEP stabilization loop for 160
      kHz pulse repetition rate in the few cycle regime.

PMID- 21964142
TI  - Absolute frequency spectroscopy of CO2 lines at around 2.09 MUm by combined use
      of an Er:fiber comb and a Ho:YLF amplifier.
AB  - The low-frequency tail of an octave-spanning supercontinuum (SC) generated by an
      Er:fiber comb is enhanced by a multipass Ho:YLF amplifier and used in a sum
      frequency-generation scheme to obtain absolute referencing of a single-mode Tm
      Ho:YAG laser tunable around 2.09 MUm. By tuning the comb repetition frequency,
      the probing laser is scanned across the absorption lines of a CO(2) gas sample
      and highly accurate absorption profiles are measured. This approach can be
      readily scaled to any wavelength above ~2 MUm.

PMID- 21964143
TI  - Transmission enhanced optical lenses with self-organized antireflective
      subwavelength structures for the UV range.
AB  - We present transmission increased fused silica lenses produced by using self
      organized antireflective structures for which we developed an efficient
      manufacturing process. The spectral transmission measured over the whole lens
      aperture shows a significant transmission enhancement of up to 3.5% in the UV
      range. Local measurements on the lens's surface reveal a strongly reduced
      reflection of below 0.1% for 300 nm wavelength, which is homogeneous over the
      whole lens. Further, the lenses show a broadband spectral antireflection
      behavior. For 600 nm wavelength the reflection was measured at about 1%.

PMID- 21964144
TI  - High-speed CH planar laser-induced fluorescence imaging using a multimode-pumped
      optical parametric oscillator.
AB  - We report on high-speed CH planar laser-induced fluorescence (PLIF) imaging in
      turbulent diffusion flames using a multimode-pumped optical parametric oscillator
      (OPO). The OPO is pumped by the third-harmonic output of a multimode Nd:YAG
      cluster for direct signal excitation in the A-X (0,0) band of the CH radical. The
      lasing threshold, conversion efficiency, and linewidth are shown to depend on the
      number of pump passes in the ring cavity of the OPO. Single-shot CH PLIF images
      are acquired at 10 kHz with excitation energy up to 6 mJ/pulse at 431.1 nm.
      Signal-to-noise ratios of ~25-35 are the highest yet reported for high-speed CH
      PLIF.

PMID- 21964145
TI  - Subwavelength-size solid immersion lens.
AB  - We report on the fabrication and characterization of nanoscale solid immersion
      lenses (nano-SILs) with sizes down to a subwavelength range. Submicrometer-scale
      cylinders fabricated by electron-beam lithography are thermally reflowed to form
      a spherical shape. Subsequent soft lithography leads to nano-SILs on transparent
      substrates for optical characterization. The optical characterization is
      performed using a high-resolution interference microscope with illumination at
      642 nm wavelength. The focal spots produced by the nano-SILs show both spot-size
      reduction and enhanced optical intensity, which are consistent with the immersion
      effect.

PMID- 21964146
TI  - Estimation of reflectance from camera responses by the regularized local linear
      model.
AB  - Because of the limited approximation capability of using fixed basis functions,
      the performance of reflectance estimation obtained by traditional linear models
      will not be optimal. We propose an approach based on the regularized local linear
      model. Our approach performs efficiently and knowledge of the spectral power
      distribution of the illuminant and the spectral sensitivities of the camera is
      not needed. Experimental results show that the proposed method performs better
      than some well-known methods in terms of both reflectance error and colorimetric
      error.

PMID- 21964147
TI  - Efficient parametric interactions in a low loss GaInP photonic crystal waveguide.
AB  - We describe time domain characterizations of dynamic four-wave mixing in a low
      loss modified W1 GaInP photonic crystal waveguide. Using 32 ps wide pump pulses
      with peak powers of up to 1.1 W we achieved a very large conversion efficiency of
      -6.8 dB as well as a 1.3 dB parametric gain experienced by a weak CW probe
      signal. Time domain simulations confirm quantitatively all the measured results.

PMID- 21964148
TI  - Simultaneous measurement of curvature and strain using a suspended multicore
      fiber.
AB  - A suspended multicore fiber sensor for simultaneous measurement of curvature and
      strain is proposed. The spectral response shows evidences of several
      interferences arising from the seven cores of the fiber. Once the sensing head
      presents different sensitivities for curvature and strain measurements, these
      physical parameters can be discriminated by using the matrix method. The rms
      deviations are +/-19 m(-1) and +/-12.90 MUepsilon for curvature and strain
      measurements, respectively.

PMID- 21964149
TI  - Optical spin-dependent angular shift in structured metamaterials.
AB  - The physics behind the spin (polarization)-dependent electromagnetic hot-spot
      phenomenon is due to the presence of the geometric phase resulting from the
      optical spin-orbit interaction in the interaction of light with the subwavelength
      microstructures. Unlike the tiny spin-dependent shift of light associated with
      the usual spin-Hall effect of light, here we present the distinct polarization
      dependent angular shift by employing an array of subwavelength metallic
      apertures. More importantly, this novel electromagnetic precession is accompanied
      by the extraordinary optical transmission phenomenon and offers the exciting
      possibilities for novel applications for subwavelength structured metallic
      systems.

PMID- 21964150
TI  - Cavity-based Fabry-Perot probe with protruding subwavelength aperture.
AB  - We investigate numerically and experimentally the possibility of development of a
      cavity-based probe for near-field optical microscopy systems based on a fiber
      Fabry-Perot interferometer with a subwavelength protruding aperture. It was shown
      that the probe provides a spatial resolution of no worse than lambda/37 for
      lambda=1550 nm.

PMID- 21964151
TI  - Penalty-free transmission in a silicon coupled resonator optical waveguide over
      the full C-band.
AB  - We show that optical signal propagation in a coupled resonator optical waveguide
      (CROW) does not introduce additional performance penalties with respect to
      propagation in a conventional optical waveguide. The result is demonstrated in a
      low-loss (1 dB) eight-ring silicon CROW by means of bit error rate measurements
      performed over the whole telecommunication C-band. An extensive characterization
      of the CROW parameters in terms of insertion loss, bandwidth, in-band intensity
      ripple, crosstalk, and sensitivity to thermal drifts is presented.

PMID- 21964152
TI  - Ultraviolet true zero-order wave plate made of birefringent porous silica.
AB  - Porous Si made from (110) Si wafers exhibits strong in-plane optical anisotropy
      (birefringence) in the visible and near-IR ranges. Oxidation of the birefringent
      porous Si results in the formation of birefringent porous silica. We demonstrate
      that the degree of the birefringence of porous silica can be controlled by the
      oxidation condition, and very small birefringence can be achieved. The smallest
      anisotropy of the refractive index (Deltan) is 0.001, which is about ten times
      smaller than that of quartz. The small birefringence allows us to produce true
      zero-order wave plates operating in the UV range.

PMID- 21964153
TI  - Body temperature patterns in two syntopic elephant shrew species during winter.
AB  - We measured body temperature (T(b)) in free-ranging individuals of two species of
      elephant shrews, namely western rock elephant shrews (Elephantulus rupestris) and
      Cape rock elephant shrews (E. edwardii), during winter in a winter-rainfall
      region of western South Africa. These syntopic species have similar ecologies and
      morphologies and thus potential for large overlaps in diet and habitat use.
      Unexpectedly, they displayed different T(b) patterns. Western rock elephant
      shrews were heterothermic, with all individuals decreasing T(b) below 30 degrees
      C on at least 34% of nights. The level of heterothermy expressed was similar to
      other species traditionally defined as daily heterotherms and was inversely
      related to T(a), as is commonly seen in small heterothermic endotherms. In
      contrast, Cape rock elephant shrews rarely allowed their T(b) to decrease below
      30 degrees C. The level of heterothermy was similar to species traditionally
      defined as homeotherms and there was no relationship between the level of
      heterothermy expressed and T(a). In both species, the minimum daily T(b) was
      recorded almost exclusively at night, often shortly before sunrise, although in
      some individuals minimum T(b) occasionally occurred during the day. The
      interspecific variation in T(b) patterns among Elephantulus species recorded to
      date reiterates the importance of ecological determinants of heterothermy that
      interact with factors such as body mass and phylogeny.

PMID- 21964154
TI  - CFTR mediated chloride secretion in the avian renal proximal tubule.
AB  - In primary cell cultures of the avian (Gallus gallus) renal proximal tubule
      parathyroid hormone and cAMP activation generate a Cl(-)-dependent short circuit
      current (I(SC)) response, consistent with net transepithelial Cl(-) secretion. In
      this study we investigated the expression and physiological function of the Na-K
      2Cl (NKCC) transporter and CFTR chloride channel, both associated with Cl(-)
      secretion in a variety of tissues, in these proximal tubule cells. Using both RT
      PCR and immunoblotting approaches, we showed that NKCC and CFTR are expressed,
      both in proximal tubule primary cultures and in a proximal tubule fraction of non
      cultured (native tissue) fragments. We also used electrophysiological methods to
      assess the functional contribution of NKCC and CFTR to forskolin-activated I(SC)
      responses in filter grown cultured monolayers. Bumetanide (10 MUM), a specific
      blocker of NKCC, inhibited forskolin activated I(SC) by about 40%, suggesting
      that basolateral uptake of Cl(-) is partially mediated by NKCC transport. In
      monolayers permeabilized on the basolateral side with nystatin, forskolin
      activated an apical Cl(-) conductance, manifested as bidirectional diffusion
      currents in the presence of oppositely directed Cl(-) gradients. Under these
      conditions the apical conductance appeared to show some bias towards apical-to
      basolateral Cl(-) current. Two selective CFTR blockers, CFTR Inhibitor 172 and
      GlyH-101 (both at 20 MUM) inhibited the forskolin activated diffusion currents by
      38-68%, with GlyH-101 having a greater effect. These data support the conclusion
      that avian renal proximal tubules utilize an apical CFTR Cl(-) channel to mediate
      cAMP-activated Cl(-) secretion.

PMID- 21964155
TI  - A putative G protein-coupled receptor involved in innate immune defense of
      Procambarus clarkii against bacterial infection.
AB  - The immune functions of G protein-coupled receptor (GPCR) were widely
      investigated in mammals. However, limited researches on immune function of GPCRs
      were reported in invertebrates. In the present study, the immune functions of
      HP1R gene, a putative GPCR identified from red swamp crayfish Procambarus clarkii
      were reported. Expression of HP1R gene was significant up-regulated in response
      to heat-killed Aeromonas hydrophila challenge. HP1R gene silencing mediated by
      RNA interference significantly enhanced the susceptibility of red swamp crayfish
      to A. hydrophila and Vibrio alginolyticus, indicating that HP1R was required for
      red swamp crayfish to defend against bacterial challenge. In HP1R-silenced
      crayfish, increased bacterial burden and decreased THC in response to bacterial
      challenge were observed when compared with control crayfish. No significant
      difference of proPO gene expression was observed between HP1R-silenced and
      control crayfish after challenge with heat-killed A. hydrophila. However, PO
      activity in response to bacterial challenge was significantly reduced in HP1R
      silenced crayfish. The results collectively indicated that HP1R was an important
      immune molecule which was required for red swamp crayfish to defend against
      bacterial infection.

PMID- 21964156
TI  - Calpain inhibition attenuates angiotensin II-induced abdominal aortic aneurysms
      and atherosclerosis in low-density lipoprotein receptor-deficient mice.
AB  - Chronic infusion of angiotensin II (AngII) augments atherosclerosis and abdominal
      aortic aneurysm (AAA) formation in hypercholesterolemic mice. AngII-induced AAAs
      are associated with medial macrophage accumulation and matrix metalloproteinase
      (MMP) activation. Inhibition of calpain, a calcium-activated neutral cysteine
      protease, by overexpression of its endogenous inhibitor, calpastatin, attenuates
      AngII-induced leukocyte infiltration, perivascular inflammation, and MMP
      activation in mice. The purpose of this study was to define whether
      pharmacological inhibition of calpain influences AngII-induced AAAs in
      hypercholesterolemic mice. Male low-density lipoprotein receptor-/- mice were fed
      a fat-enriched diet and administered with either vehicle or a calpain-specific
      inhibitor, BDA-410 (30 mg/kg per day) for 5 weeks. After 1 week of feeding, mice
      were infused with AngII (1000 ng/kg per minute) for 4 weeks. AngII-infusion
      profoundly increased aortic calpain protein and activity. BDA-410 administration
      had no effect on plasma cholesterol concentrations or AngII-increased systolic
      blood pressure. Calpain inhibition significantly attenuated AngII-induced AAA
      formation and atherosclerosis development. BDA-410 administration attenuated
      activation of MMP12, proinflammatory cytokines (IL-6, monocyte chemoattractant
      protein-1), and macrophage infiltration into the aorta. BDA-410 administration
      significantly attenuated thioglycolate-elicited macrophage accumulation in the
      peritoneal cavity. We conclude that calpain inhibition using BDA-410 attenuated
      AngII-induced AAA formation and atherosclerosis development in low-density
      lipoprotein receptor-/- mice.

PMID- 21964157
TI  - Electrophysiologic profile of dronedarone on the ventricular level:  beneficial
      effect on postrepolarization refractoriness in the presence of rapid phase 3
      repolarization.
AB  - BACKGROUND: Dronedarone (D) is developed to maintain sinus rhythm in patients
      suffering from atrial fibrillation. The aim of the present study was to
      investigate, whether dronedarone also has an antiarrhythmic potential in the
      ventricle and to elucidate the mechanisms for its low proarrhythmic potential in
      an experimental whole heart model. METHODS AND RESULTS: Thirty-five rabbits
      underwent chronic treatment with D (n = 15; 50 mg . kg(-1) . d(-1)) and
      amiodarone (A; n = 20; 50 mg . kg(-1) . d(-1)). Hearts were perfused on a
      Langendorff apparatus. Results were compared with hearts acutely treated with
      sotalol (S; 50-100 MUM; n = 14). A 12-lead electrocardiogram and up to 8
      ventricular epi- and endocardial monophasic action potentials showed a
      significant prolongation of QT interval (D: +24 milliseconds, A: +28
      milliseconds, S: +35 milliseconds (50 MUM), +56 milliseconds (100 MUM); P < 0.02)
      compared with baseline. In contrast to D and A, S led to a significant increase
      in dispersion of repolarization and exhibited reverse use dependence. D, A, and S
      increased refractory period, resulting in a significant increase in
      postrepolarization refractoriness (effective refractory period minus action
      potential duration; D = +12 milliseconds; A = +14 milliseconds; S = +25
      milliseconds; P < 0.05). S led to a triangular action potential configuration,
      whereas D and A caused a fast phase 3 prolongation. After lowering of potassium
      concentration, 50% of S-treated hearts showed torsade de pointes, in contrast to
      an absence of torsade de pointes in D and A. CONCLUSIONS: Prolongation of
      myocardial repolarization and postrepolarization refractoriness by D may act
      antiarrhythmic. A fast phase 3 repolarization in the absence of both increased
      dispersion of repolarization and reverse use dependence prevents proarrhythmia.

PMID- 21964158
TI  - Naringin ameliorates atherogenic dyslipidemia but not hyperglycemia in rats with
      type 1 diabetes.
AB  - Antiatherogenic and hypoglycemic effects of naringin are hereby investigated in
      type 1 diabetes. Wistar rats (n = 6) were treated daily with 1.0 mL of water
      (group 1), naringin (50 mg/kg) (groups 2 and 3, respectively), regular insulin (4
      U/kg, subcutaneously, twice daily) (group 4), and simvastatin (20 mg/kg) (group
      6). Groups 3, 4, 5, and 6 exhibited polydipsia and hyperglycemia after injection
      with streptozotocin (60 mg/kg body weight). Insulin, but not naringin,
      significantly lowered fasting blood glucose levels in diabetic rats. Plasma low
      density lipoprotein cholesterol concentrations were significantly higher in
      nontreated diabetic rats (group 5) compared with control (group 1), whereas total
      and high-density lipoprotein cholesterol were significantly higher in naringin-
      and simvastatin-treated diabetic rats, respectively. Hepatic total cholesterol
      and triglycerides were significantly elevated in nontreated diabetic compared
      with the control, naringin-, insulin-, and simvastatin-treated diabetic rats,
      respectively. Hepatic 3-hydroxy-3-methyl-glutaryl CoA reductase and Acyl
      CoA:cholesterol acyltransferase activities were significantly elevated in
      nontreated diabetic compared with the control, naringin-, and simvastatin-treated
      diabetic rats, respectively. However, plasma low-density lipoprotein to high
      density lipoprotein ratio was significantly higher in nontreated diabetic
      compared with the control, whereas naringin and simvastatin significantly reduced
      the ratio in diabetic rats. Naringin is not hypoglycemic but improves atherogenic
      index in type 1 diabetes.

PMID- 21964160
TI  - Introduction of abnormal N-heterocyclic carbene as an efficient organocatalyst:
      ring opening polymerization of cyclic esters.
AB  - The recently isolated abnormal N-heterocyclic carbene (aNHC) has been established
      as an efficient organocatalyst in ring opening polymerization of three different
      cyclic esters rac-lactide (rac-LA), epsilon-caprolactone (epsilon-CL), and delta
      valerolactone (delta-VL). Preliminary DFT calculations indicate that aNHC can be
      a better organocatalyst than the corresponding nNHC counterpart.

PMID- 21964159
TI  - Postconditioning modulates ischemia-damaged mitochondria during reperfusion.
AB  - Cardiac ischemia damages the mitochondrial electron transport chain and the
      damage persists during reperfusion. Ischemic postconditioning (PC), applied
      during early reperfusion, decreases cardiac injury. This finding suggests that
      the ischemia-damaged mitochondria can be regulated to decrease cardiac injury.
      The reversible blockade of electron transport during ischemia prevents damage to
      mitochondria. We propose that the targets of PC cytoprotective signaling are
      mitochondria damaged by ischemia. Thus, if ischemia-mediated mitochondrial damage
      is prevented, PC at the onset of reperfusion will not result in additional
      protection. Isolated, Langendorff-perfused adult rat hearts underwent 25-minute
      global ischemia and 30-minute reperfusion. Amobarbital (2.5 mM) was used to
      reversibly inhibit electron transport during ischemia. PC (6 cycles of 10-second
      ischemia-reperfusion) was applied at the onset of reperfusion. Subsarcolemmal and
      interfibrillar mitochondria were isolated after reperfusion. Blockade of electron
      transport with amobarbital only during ischemia preserved oxidative
      phosphorylation and decreased myocardial injury. PC, after untreated ischemia,
      decreased cardiac injury without improvement of oxidative phosphorylation.
      Blockade of electron transport during ischemia or PC improved calcium tolerance
      and inner membrane potential in subsarcolemmal mitochondria after reperfusion. In
      hearts treated with amobarbital before ischemia, PC did not provide further
      protection. Thus, PC protects myocardium via the regulation of ischemia-damaged
      mitochondria during early reperfusion.

PMID- 21964162
TI  - Extent, nature and hospital costs of fireworks-related injuries during the
      Wednesday Eve festival in Iran.
AB  - BACKGROUND: Fireworks are commonly used in local and national celebrations. The
      aim of this study is to explore the extent, nature and hospital costs of injuries
      related to the Persian Wednesday Eve festival in Iran. METHODS: Data for injuries
      caused by fireworks during the 2009 Persian Wednesday Eve festival were collected
      from the national Ministry of Health database. Injuries were divided into nine
      groups and the average and total hospital costs were estimated for each group.
      The cost of care for patients with burns was estimated by reviewing a sample of
      100 patients randomly selected from a large burn center in Tehran. Other costs
      were estimated by conducting semi structured interviews with expert managers at
      two large government hospitals. RESULTS: 1817 people were injured by fireworks
      during the 2009 Wednesday Eve festival. The most frequently injured sites were
      the hand (43.3%), eye (24.5%) and face (13.2%), and the most common types of
      injury were burns (39.9%), contusions/abrasions (24.6%) and lacerations (12.7%).
      The mean length of hospital stay was 8.15 days for patients with burns, 10.7 days
      for those with amputations, and 3 days for those with other types of injury. The
      total hospital cost of injuries was US$ 284 000 and the average cost per injury
      was US$ 156. The total hospital cost of patients with amputations was US$ 48 598.
      Most of the costs were related to burns (56.6%) followed by amputations (12.2%).
      CONCLUSIONS: Injuries related to the Persian Wednesday Eve festival are common
      and lead to extensive morbidity and medical costs.    (c) 2013 KUMS, All rights
      reserved.

PMID- 21964161
TI  - Trimethyltin chloride (TMT) neurobehavioral toxicity in embryonic zebrafish.
AB  - Trimethyltin chloride (TMT) is a neurotoxicant that is widely present in the
      aquatic environment, primarily from the manufacture of PVC plastic, but few
      studies have evaluated aquatic neurotoxicity. We have examined TMT dose-dependent
      malformation and neurobehavioral toxicity in the embryonic zebrafish model.
      Exposure of embryos to TMT (0-10 MUM) from 48 to 72 hours post fertilization
      (hpf) elicited a concentration-related increase (0-100%) in malformation
      incidence with an EC(25) of 5.55 MUM. TMT also significantly modulated the
      frequency of tail flexion, the earliest motor behavior observed in developing
      zebrafish, and the ability to respond to a mechanical tail touch. Exposure to 5
      MUM TMT from 48 to 72 hpf modulated the photomotor response at 4 and 5 days post
      fertilization and significantly promoted apoptosis in the tail. Our study
      demonstrates the morphological and behavioral sensitivity of the developing
      zebrafish to TMT and establishes a platform for future identification of the
      affected pathways and chemical modulators of TMT toxicity.

PMID- 21964163
TI  - Radio telemetry devices to monitor breathing in non-sedated animals.
AB  - Radio telemetry equipment has significantly improved over the last 10-15 years
      and is increasingly being used in research for monitoring a variety of
      physiological parameters in non-sedated animals. The aim of this review is to
      provide an update on the current state of development of radio telemetry for
      recording respiration. Our literature review found only rare reports of
      respiratory studies via radio telemetry. Much of this article will hence report
      our experience with our custom-built radio telemetry devices designed for
      recording respiratory signals, together with numerous other physiological signals
      in lambs. Our current radio telemetry system allows to record 24 simultaneous
      signals 24h/day for several days. To our knowledge, this is the highest number of
      physiological signals, which can be recorded wirelessly. Our devices have been
      invaluable for studying respiration in our ovine models of preterm birth, reflux
      laryngitis, postnatal exposure to cigarette smoke, respiratory syncytial virus
      infection and nasal ventilation, all of which are relevant to neonatal
      respiratory problems.

PMID- 21964164
TI  - New hope for type 2 diabetics: targeting insulin resistance through the immune
      modulation of stem cells.
AB  - The prevalence of type 2 diabetes (T2D) is increasing worldwide, highlighting the
      need for a better understanding of the pathogenesis of the disease and the
      development of innovative therapeutic approaches for the prevention and cure of
      the condition. Mounting evidence points to the involvement of immune dysfunction
      in insulin resistance in T2D, suggesting that immune modulation may be a useful
      tool in treating the disease. Recent advances in the use of adult stem cells from
      human umbilical cord blood and bone marrow for immune modulation hold promise for
      overcoming immune dysfunction in T2D without many of the complications associated
      with traditional immunosuppressive therapies. This review focuses on recent
      progress in the use of immune modulation in T2D and discusses the potential for
      future therapies. New insights are provided on the use of cord blood-derived
      multipotent stem cells (CB-SC) in T2D.

PMID- 21964165
TI  - Monocytic HLA DR antigens in schizophrenic patients.
AB  - A genetic association of specific human leukocyte antigens (HLA) DR genes and
      schizophrenia has recently been shown. These HLA play a fundamental role in the
      control of immune responses. Furthermore infectious agents have been proposed to
      be involved in the pathogenesis of schizophrenia. In this study we investigated
      the rate of HLA DR positive monocytes in schizophrenic patients compared to
      controls with a special focus on the adaption to in vitro stimulation with toll
      like receptor ligands. Patients with schizophrenia and matched controls were
      included. For each individual, we evaluated the rate of HLA DR positive monocytes
      (either incubated at 37  degrees C or after stimulation with lipopolysaccharide
      or Poly I:C). We found a significantly higher percentage of schizophrenic
      patients with elevated HLA DR positive cells (p=0.045) as compared to controls.
      The adjustment rate from baseline levels of monocytic HLA DR positive cells to
      stimulation with Poly I:C was significantly lower in schizophrenic patients
      (p=0.038). The increased monocytic HLA DR in schizophrenic patients and the
      maladjustment of their monocytic HLA DR levels to an infectious stimulus might be
      a sign for a disturbed monocytic immune balance in schizophrenic individuals.

PMID- 21964166
TI  - The utilisation of radiology for the teaching of anatomy in Canadian medical
      schools.
AB  - OBJECTIVE: To determine the utilisation of diagnostic imaging (radiology) as a
      department and/or imaging medium in the teaching of anatomy at the Canadian
      undergraduate medical education level. METHODS: The study objectives were
      achieved through the use of a questionnaire and a literature review. The anatomy
      department head at each English-based Canadian Medical School was contacted, and
      the individual most responsible for anatomy teaching in the medical school
      curriculum was identified. This individual was subsequently asked to complete a
      questionnaire that evaluated the involvement of radiology for anatomy teaching in
      their curriculum. RESULTS: The use and integration of radiology is a common
      practice in the teaching of anatomy in Canadian undergraduate medicine. Although
      the methods and extent of its use varied among institutions, every English-based
      Canadian medical school, except one, was using diagnostic imaging material in
      their instruction of anatomy. Furthermore, half of the institutions had a
      radiologist as a faculty member of their anatomy department to help teach and to
      use imaging to its full potential. DISCUSSION: This audit of anatomy departments
      suggests that diagnostic imaging has an important role to play in anatomy
      teaching in Canadian English-speaking medical schools.

PMID- 21964168
TI  - Primary antiphospholipid antibody syndrome and Libmann-Sachs endocarditis.

PMID- 21964169
TI  - Medicine is a social science in its very bone and marrow.

PMID- 21964170
TI  - Impact of direct-to-consumer predictive genomic testing on risk perception and
      worry among patients receiving routine care in a preventive health clinic.
AB  - OBJECTIVE: To assess the impact of direct-to-consumer (DTC) predictive genomic
      risk information on perceived risk and worry in the context of routine clinical
      care. PATIENTS AND METHODS: Patients attending a preventive medicine clinic
      between June 1 and December 18, 2009, were randomly assigned to receive either
      genomic risk information from a DTC product plus usual care (n=74) or usual care
      alone (n=76). At intervals of 1 week and 1 year after their clinic visit,
      participants completed surveys containing validated measures of risk perception
      and levels of worry associated with the 12 conditions assessed by the DTC
      product. RESULTS: Of 345 patients approached, 150 (43%) agreed to participate, 64
      (19%) refused, and 131 (38%) did not respond. Compared with those receiving usual
      care, participants who received genomic risk information initially rated their
      risk as higher for 4 conditions (abdominal aneurysm [P=.001], Graves disease
      [P=.04], obesity [P=.01], and osteoarthritis [P=.04]) and lower for one (prostate
      cancer [P=.02]). Although differences were not significant, they also reported
      higher levels of worry for 7 conditions and lower levels for 5 others. At 1 year,
      there were no significant differences between groups. CONCLUSION: Predictive
      genomic risk information modestly influences risk perception and worry. The
      extent and direction of this influence may depend on the condition being tested
      and its baseline prominence in preventive health care and may attenuate with
      time.

PMID- 21964171
TI  - Unexplained drownings and the cardiac channelopathies: a molecular autopsy
      series.
AB  - OBJECTIVE: To determine the prevalence and spectrum of mutations associated with
      long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia
      (CPVT) in a seemingly unexplained drowning cohort. PATIENTS AND METHODS: From
      September 1, 1998, through October 31, 2010, 35 unexplained drowning victims (23
      male and 12 female; mean +/- SD age, 17+/-12 years [range, 4-69 years]) were
      referred for a cardiac channel molecular autopsy. Of these, 28 (20 male and 8
      female) drowned while swimming, and 7 (3 male and 4 female) were bathtub
      submersions. Polymerase chain reaction, denaturing high-performance liquid
      chromatography, and DNA sequencing were used for a comprehensive mutational
      analysis of the 3 major LQTS-susceptibility genes (KCNQ1, KCNH2, and SCN5A), and
      a targeted analysis of the CPVT1-associated, RYR2-encoded cardiac ryanodine
      receptor was conducted. RESULTS: Of the 28 victims of swimming-related drowning,
      8 (28.6%) were mutation positive, including 2 with KCNQ1 mutations (L273F,
      AAPdel71-73 plus V524G) and 6 with RYR2 mutations (R414C, I419F, R1013Q, V2321A,
      R2401H, and V2475F). None of the bathtub victims were mutation positive. Of the
      28 victims who drowned while swimming, women were more likely to be mutation
      positive than men (5/8 [62.5%] vs 3/20 [15%]; P=.02). Although none of the
      mutation-positive, swimming-related drowning victims had a premortem diagnosis of
      LQTS or CPVT, a family history of cardiac arrest, family history of prior
      drowning, or QT prolongation was present in 50%. CONCLUSION: Nearly 30% of the
      victims of swimming-related drowning hosted a cardiac channel mutation. Genetic
      testing should be considered in the postmortem evaluation of an unexplained
      drowning, especially if a positive personal or family history is elicited.

PMID- 21964172
TI  - MAP0004, orally inhaled dihydroergotamine for acute treatment of migraine:
      efficacy of early and late treatments.
AB  - OBJECTIVE: To evaluate the efficacy of MAP0004, an orally inhaled
      dihydroergotamine, for acute treatment of migraine when administered at various
      time points from within 1 hour to more than 8 hours after migraine onset.
      PATIENTS AND METHODS: This post hoc subanalysis was conducted using data from 902
      patients enrolled in a randomized, double-blind, placebo-controlled, 2-arm, phase
      3, multicenter study conducted from July 14, 2008, through March 23, 2009. End
      points were 2-hour pain relief and pain-free rates in patients who treated a
      migraine in <=1 hour, from >1 hour to <=4 hours, from >4 to <=8 hours, or in >8
      hours after onset of migraine, given that patients may be unwilling or unable to
      initiate treatment at headache inception. RESULTS: Treatment with MAP0004 was
      significantly more effective than placebo in relieving pain at all treatment
      points (<=1 hour after start of migraine: 66% [74/112] for MAP0004 vs 41%
      [48/118] for placebo, P<.001; >1 to <=4 hours: 60% [91/153] vs 35% [58/168],
      P<.001; >4 to <=8 hours: 53% [36/68] vs 30% [16/54], P=.008; and >8 hours: 48%
      [25/52] vs 24% [11/46], P=.007). Pain-free rates were also significantly higher
      with MAP0004 than placebo for treatment within 8 hours after migraine onset (<=1
      hour: 38% [43/112] for MAP0004 vs 13% [15/118] for placebo, P<.001; >1 to <=4
      hours: 28% [43/153] vs 10% [17/168], P<.001; >4 to <=8 hours: 22% [15/68] vs 7%
      [4/54], P<.025) but not at >8 hours (19% [10/52] vs 9% [4/46], P=.106).
      CONCLUSION: This post hoc subanalysis shows that MAP0004 was effective in
      treating migraine irrespective of the time of treatment, even more than 8 hours
      after onset of migraine pain.

PMID- 21964173
TI  - Ethnic differences in cardiovascular risks and mortality in atherothrombotic
      disease: insights from the Reduction of Atherothrombosis for Continued Health
      (REACH) registry.
AB  - OBJECTIVE: To determine whether ethnic-specific differences in the prevalence of
      cardiovascular risk factors and outcomes exist worldwide among individuals with
      stable arterial disease. PATIENTS AND METHODS: From December 1, 2003, to June 30,
      2004, the prospective, observational REduction of Atherothrombosis for Continued
      Health (REACH) Registry enrolled 49,602 out-patients with coronary artery
      disease, cerebrovascular disease, and/or peripheral arterial disease from 7
      predefined ethnic/racial groups: white, Hispanic, East Asian, South Asian, Other
      Asian, black, and Other (comprising any race distinct from those specified). The
      baseline demographic and risk factor profiles, medication use, and 2-year
      cardiovascular outcomes were assessed among these groups. RESULTS: The prevalence
      of traditional atherothrombotic risk factors varied significantly among the
      ethnic/racial groups. The use of medical therapies to reduce risk was comparable
      among all groups. At 2-year follow-up, the rate of cardiovascular death was
      significantly higher in blacks (6.1%) compared with all other ethnic/racial
      groups (3.9%; P=.01). Cardiovascular death rates were significantly lower in all
      3 Asian ethnic/racial groups (overall, 2.1%) compared with the other groups
      (4.5%; P<.001). CONCLUSION: The REACH Registry, a large international study of
      individuals with atherothrombotic disease, documents the important ethnic
      specific differences in cardiovascular risk factors and variations in
      cardiovascular mortality that currently exist worldwide.

PMID- 21964174
TI  - Health reform: a community experience using design research as a guide.
AB  - Meaningful health reform in the United States must improve the health of the
      population while lowering costs. In an effort to provide a framework for doing
      so, the Institute of Health Care Improvement created the triple aim, which
      encompasses the goals of (1) improving individual health and experience with the
      health care system, (2) improving population health, and (3) decreasing the rate
      of per capita health care costs. Current reform efforts have focused on the
      development of Patient-Centered Medical Homes (an innovative team-based model of
      care that facilitates a partnership between the patient's personal physician
      coordinating care throughout a patient's lifetime to maximize health outcomes),
      but these relatively narrow efforts are focused on office practice and payment
      methods and are not generally oriented toward community needs. We sought to apply
      design research in assessing a community opportunity to apply the triple aim as a
      strategy to transform health care delivery. Mixed methodology provides greater
      insight into the unexpressed health needs of individuals and into the creation of
      delivery systems more likely to achieve the triple aim. In a small, midwestern
      town, a mixed methods approach was used to assess community health needs to
      facilitate design and implementation of care delivery systems. The research
      findings suggest that health system design concepts should focus on the creation
      of health, not health care; foster simplicity; create nurturing relationships;
      eliminate user fear; and contain costs. These observations can be helpful to
      health care professionals who are developing new methods of care delivery and
      policymakers and payers contemplating new payment systems to achieve the goals of
      the triple aim.

PMID- 21964176
TI  - Gastric banding: ethical dilemmas in reviewing body mass index thresholds.

PMID- 21964175
TI  - Circulating serologic and molecular biomarkers in malignant melanoma.
AB  - The worldwide incidence of malignant melanoma has been increasing during the past
      decade and is a public health concern because this disease accounts for up to 90%
      of deaths from cutaneous malignancies. It remains a devastating disease with few
      therapeutic options once in an advanced stage. Current methods of detection,
      prognostication, and monitoring of melanoma focus on clinical, morphologic, and
      histopathologic characteristics of measurable tumor. Although this information
      provides some insight into disease behavior and outcome, melanoma is still an
      unpredictable disease. Significant effort has been put into finding an
      informative serologic biomarker. However, the marker remains elusive, and
      investigations continue. Using the PubMed database, we reviewed the published
      literature on serologic melanoma biomarkers and present a synopsis of the
      extensive investigations that have been performed thus far, provide some insight
      into why most have failed to become incorporated into routine clinical use, and
      present an overview of innovative methods currently being explored.

PMID- 21964177
TI  - 73-year-old man with increasing abdominal girth and dyspnea.

PMID- 21964178
TI  - Corticosteroids in the treatment of alcohol-induced rhabdomyolysis.
AB  - Rhabdomyolysis is a common condition with potentially devastating complications,
      including acute renal failure, arrhythmias, and death. The standard of care is to
      use supportive measures such as aggressive fluid repletion to prevent kidney
      injury and attenuate clinical symptoms. Besides fluid management, few therapeutic
      options are available for the treatment of acute rhabdomyolysis. As a result,
      acute and refractory cases remain difficult to manage. We report a case of
      alcohol-induced rhabdomyolysis that responded dramatically to high-dose
      corticosteroids. A 55-year-old man presented to the emergency department for
      evaluation of diffuse muscle pain, weakness, and darkening urine. On admission,
      his creatine kinase (CK) level was 50,022 U/L. Despite aggressive fluid
      repletion, his CK level continued to increase, peaking at 401,280 U/L with a
      concomitant increase in muscle pain and urine darkening. On administration of
      high-dose corticosteroids, clinical symptoms and CK levels improved dramatically,
      and the patient was discharged 36 hours later with complete resolution of muscle
      pain and weakness. Given their low toxicity profile, short-term high-dose
      corticosteroids may be a valid treatment option for recurrent rhabdomyolysis
      unresponsive to fluid repletion.

PMID- 21964180
TI  - Eosinophilic ascites resolution with ketotifen.

PMID- 21964181
TI  - Secondhand smoke levels in public building main entrances: outdoor and indoor
      PM2.5 assessment.
AB  - BACKGROUND/OBJECTIVES: To describe secondhand smoke (SHS) levels in halls and
      main entrances (outdoors) in different buildings by measurement of PM(2.5) and
      airborne nicotine. METHODS: Cross-sectional study in a sample of 47 public
      buildings. The authors studied SHS levels derived from PM(2.5) (micrograms per
      cubic metre) using TSI SidePak Personal Aerosol Monitors. The authors tested four
      locations within buildings: hall, main entrance (outdoor), control (indoor) and
      control (outdoor). The authors also measured airborne nicotine concentration
      (micrograms per cubic metre) in main entrances (outdoor). The authors computed
      medians and IQRs to describe the data. Spearman correlation coefficient (rsp) was
      used to explore the association between PM(2.5) concentrations simultaneously
      measured in halls and main entrances as well as between PM(2.5) and nicotine
      concentrations. RESULTS: The authors obtained an overall median PM(2.5)
      concentration of hall 18.20 MUg/m(3) (IQR: 10.92-23.92 MUg/m(3)), main entrance
      (outdoor) 17.16 MUg/m(3) (IQR: 10.92-24.96 MUg/m(3)), control (indoor) 10.40
      MUg/m(3) (IQR: 6.76-15.60 MUg/m(3)) and control (outdoor) 13.00 MUg/m(3) (IQR:
      8.32-18.72 MUg/m(3)). The PM(2.5) concentration in halls was more correlated with
      concentration in the main entrances (outdoors) (rsp=0.518, 95% CI 0.271 to 0.701)
      than with the control indoor (rsp=0.316, 95% CI 0.032 to 0.553). The Spearman
      correlation coefficient between nicotine and PM(2.5) concentration was 0.365 (95%
      CI -0.009 to 0.650). CONCLUSIONS: Indoor locations where smoking is banned are
      not completely free from SHS with levels similar to those obtained in the
      immediate entrances (outdoors) where smoking is allowed, indicating that SHS from
      outdoors settings drifts to adjacent indoors. These results warrant a revision of
      current smoke-free policies in particular outdoor settings.

PMID- 21964182
TI  - Evaluation of apoptotic effect of cyclic imide derivatives on murine B16F10
      melanoma cells.
AB  - Cyclic imides are a large class of compounds obtained by organic synthesis
      including several sub-classes (succinimides maleimide, glutarimide, phthalimides
      naphtalimides, and its derivatives). Recently, some cyclic imide derivatives have
      shown important results as potential antitumor agents, as a Mitonafide and
      Amonafide. Based on this fact, we have studied antitumoral properties of nine
      cyclic imide derivatives, four of which are unpublished compounds, against Murine
      Melanoma Cells (B16F10). Initially, the MTT assay was used to select the compound
      with the best cytotoxic potential. After this selection, the compound 2-benzyl-1H
      benzo[de]isoquinoline-1,3(2H)-dione (4), which showed the best cytotoxic effects,
      was evaluated by flow cytometry, and a significant increase was observed in the
      proportion of cells in the subG0/G1, S and G2/M phases accompanied by a
      significant decrease in the G0/G1 phases. Then the mechanism involved on the
      death route (necrosis or apoptosis) was evaluated the by bromide and acridine
      orange method and by an Annexin V-FITC Apoptosis Detection kit. These results
      confirm that the percentage of B16F10 cells observed in the sub G0/G1 phase were
      undergoing apoptosis. The biological effects observed in the current study for
      the cyclic imide derivatives suggested promising applications, especially for the
      prototype compound 4.

PMID- 21964183
TI  - Effect of different C3-aryl substituents on the antioxidant activity of 4
      hydroxycoumarin derivatives.
AB  - The antioxidant activity of 4-hydroxycoumarin synthetic derivatives and 4
      methylumbelliferone were determined taking 4-hydroxycoumarin as the reference
      compound. Six 3-aryl-4-hydroxycoumarin derivatives were synthesized from 4
      hydroxycoumarin as precursor in order to evaluate changes in their antioxidant
      properties due to C3-aryl substituent nature. Free radical scavenging capacities
      of these compounds against two different species DPPH(.) and ABTS(.+) and the
      protecting ability towards the beta-carotene-linoleic acid co-oxidation
      enzymatically induced by lipoxygenase were measured. In addition, the
      relationship between the activities of these molecules against DPPH radical and
      the bond dissociation energy of O-H (BDE) calculated using methods of
      computational chemistry was evaluated.

PMID- 21964179
TI  - Antiviral drugs for viruses other than human immunodeficiency virus.
AB  - Most viral diseases, with the exception of those caused by human immunodeficiency
      virus, are self-limited illnesses that do not require specific antiviral therapy.
      The currently available antiviral drugs target 3 main groups of viruses: herpes,
      hepatitis, and influenza viruses. With the exception of the antisense molecule
      fomivirsen, all antiherpes drugs inhibit viral replication by serving as
      competitive substrates for viral DNA polymerase. Drugs for the treatment of
      influenza inhibit the ion channel M(2) protein or the enzyme neuraminidase.
      Combination therapy with Interferon-alpha and ribavirin remains the backbone
      treatment for chronic hepatitis C; the addition of serine protease inhibitors
      improves the treatment outcome of patients infected with hepatitis C virus
      genotype 1. Chronic hepatitis B can be treated with interferon or a combination
      of nucleos(t)ide analogues. Notably, almost all the nucleos(t) ide analogues for
      the treatment of chronic hepatitis B possess anti-human immunodeficiency virus
      properties, and they inhibit replication of hepatitis B virus by serving as
      competitive substrates for its DNA polymerase. Some antiviral drugs possess
      multiple potential clinical applications, such as ribavirin for the treatment of
      chronic hepatitis C and respiratory syncytial virus and cidofovir for the
      treatment of cytomegalovirus and other DNA viruses. Drug resistance is an
      emerging threat to the clinical utility of antiviral drugs. The major mechanisms
      for drug resistance are mutations in the viral DNA polymerase gene or in genes
      that encode for the viral kinases required for the activation of certain drugs
      such as acyclovir and ganciclovir. Widespread antiviral resistance has limited
      the clinical utility of M(2) inhibitors for the prevention and treatment of
      influenza infections. This article provides an overview of clinically available
      antiviral drugs for the primary care physician, with a special focus on
      pharmacology, clinical uses, and adverse effects.

PMID- 21964184
TI  - Novel biologically active nitro and amino substituted benzimidazo[1,2
      a]quinolines.
AB  - This manuscript described the synthesis and biological activity of novel nitro
      substituted E-2-styryl-benzimidazoles and E-2-(2-benzimidazolyl)-3
      phenylacrylonitriles and nitro and amino substituted benzimidazo[1,2-a]quinolines
      (4-5, 6-11, 17-20, and 21-32). All of the compounds showed significant growth
      inhibitory effect towards five tumor cell lines, whereby the IC(50)
      concentrations of 11, 20, 28, 29, 30, 32 are in the low micromolar range
      (IC(50)=2-19 MUM). The DNA binding experiments did not show significant affinity
      of two selected compounds towards ct-DNA. The flow cytometry analysis of
      potential cell cycle perturbations after the treatment with compounds 9, 11, 25,
      and 29 demonstrated that all of the compounds (5 MUM ~ IC(50)) significantly
      delayed the progression through G1 phase, as demonstrated by the accumulation of
      cells in G1 phase, accompanied with the reduction of the cell number in the cells
      in S phase, which does not point to DNA damage as the main mechanism of action.
      Also, fluorescence microscopy study showed cytoplasmic distribution of the
      compounds, demonstrating that DNA is not the primary target of compounds. Thus,
      considerable antiproliferative effects of studied compounds are due to
      interactions with other biological targets within cells.

PMID- 21964185
TI  - Discovery of pyridine-2-ones as novel class of multidrug resistance (MDR)
      modulators: first structure-activity relationships.
AB  - A novel facile synthesis led to pyridine-2-one target structures of which first
      series with varying substituents have been yielded and biologically characterized
      as novel multidrug resistance (MDR) modulators inhibiting P-glycoprotein (P-gp).
      Structure-activity relationships prove a dependency of the MDR-modulating
      properties from the kind and positioning of hydrogen bond acceptor functions
      within the molecular skeleton. Cyano functions turned out as biologically
      effective substituents for a potential hydrogen bonding to the protein target
      structure.

PMID- 21964186
TI  - The earliest tau dysfunction in Alzheimer's disease? Tau phosphorylated at s422
      as a toxic seed.

PMID- 21964188
TI  - Pigment epithelium-derived factor regulates early pancreatic fibrotic responses
      and suppresses the profibrotic cytokine thrombospondin-1.
AB  - Pigment epithelium-derived factor (PEDF) is important for maintaining the normal
      extracellular matrix. We hypothesized that the initiation of pancreatic fibrosis
      is dependent on the loss of PEDF. Pancreatic PEDF expression was assessed in wild
      type mice fed either a control or ethanol diet using an intragastric feeding
      model. Pancreatitis responses were elicited with either a single episode or a
      repetitive cerulein-induced (50 MUg/kg, 6 hourly i.p. injections) protocol in
      wild-type and PEDF-null mice. Quantitative real-time PCR and immunoblotting were
      performed to assess fibrogenic responses. In wild-type animals, PEDF expression
      increased with pancreatitis and was more pronounced in mice fed ethanol. Compared
      with wild-type mice, alpha-smooth muscle actin staining and expression levels of
      fibrogenic markers (eg, transforming growth factor-beta1, platelet-derived growth
      factor, collagen I, and thrombospondin-1) were higher in PEDF-null mice at
      baseline. Sirius red staining revealed more fibrosis in PEDF-null versus wild
      type pancreas 1 week after pancreatitis. Differences in tissue fibrosis resolved
      with longer recovery periods. PEDF overexpression suppressed thrombospondin-1
      levels in vitro. Ethanol feeding and experimental pancreatitis increased PEDF
      expression in wild-type mice. PEDF-null mice, however, demonstrated enhanced
      early fibrotic responses compared with wild-type mice with pancreatitis. These
      findings indicate that PEDF acts as a compensatory antifibrotic cytokine in
      pancreatitis.

PMID- 21964189
TI  - A novel enhancer of the wound healing process: the fibroblast growth factor
      binding protein.

PMID- 21964190
TI  - The role of E2F-1 and downstream target genes in mediating ischemia/reperfusion
      injury in vivo.
AB  - E2Fs are a family of transcription factors that regulate proliferation,
      differentiation and apoptosis in many cell types. E2F-1 is the prototypical E2F
      and the family member that has most often been implicated in also mediating
      apoptosis. To better understand the role of E2F-1 in mediating cardiomyocyte
      injury we initially analyzed E2F family member expression after
      ischemia/reperfusion (I/R) in vivo or simulated ischemia in vitro. I/R injury in
      vivo caused a 3.4-fold increase specifically in E2F-1 protein levels. Expression
      of other E2F family members did not change. To establish the role of E2F-1 in I/R
      we examined the response of germline deleted E2F-1 mice to I/R injury. Infarct
      size as a percentage of the area at risk was decreased 39.8% in E2F-1(-/-) mice
      compared to E2F-1(+/+) controls. Interestingly, expression of classic, E2F-1
      apoptotic target genes was not altered in E2F-1 null cardiomyocytes after I/R.
      However, upregulation of the primary member of the Forkhead family of
      transcription factors, FoxO-1a, was attenuated. Consistent, with a role for FoxO
      1a as an important target of E2F-1 in I/R, a number of proapoptotic FoxO-1a
      target genes were also altered. These results suggest that E2F-1 and FoxO-1a
      belong to a complex transcriptional network that may modulate myocardial cell
      death during I/R injury.

PMID- 21964192
TI  - Brazilian green propolis and its constituent, Artepillin C inhibits allogeneic
      activated human CD4 T cells expansion and activation.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Propolis has long been used as a popular folk
      medicine by various ethnic groups due to its wide spectrum of alleged biological
      and pharmaceutical properties including anti-microbial, anti-cancer and anti
      inflammatory functions. All these can be linked to the modulation of immune
      function. Therefore, it will be relevant for us to find out whether there is any
      novel compound that can account for such action and the mechanism involved. AIM
      OF THE STUDY: We investigated the immune modulating effect of Brazilian green
      propolis (PBrazil) and its constituent Artepillin C (Art-C) by using mixed
      leukocytes reaction. MATERIALS AND METHODS: The cytotoxic effect of Art-C on non
      tumorigenic human liver cell line miHA and non-tumorigenic human kidney cell line
      HK-2 as well as human peripheral blood mononuclear cells (PBMCs) were measured by
      XTT cell proliferation assay. The effect of PBrazil and Art-C on T cell
      proliferation and activation were determined by using carboxyfluorescein
      succinimidyl ester (CFSE) and by CD25 expression, respectively. Cytokines
      including tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma),
      interleukins such as IL-2, IL-17 were measured by intracellular cytokine staining
      and IL-10 was measured by ELISA. The effect of PBrazil and Art-C on regulatory T
      cells (Treg) induction was determined by the Foxp3 expression. The apoptotic
      effect of these compounds on CFSE labeled alloreactive T cells was measured by
      using Annexin V. RESULTS: Using mixed leukocytes reaction we demonstrated for the
      first time that both Art-C and PBrazil significantly inhibited the alloreactive
      CD4 T cell proliferation, activation, and suppressed the expressions of IL-2, IFN
      gamma and IL-17 in these alloreactive CD4 T cells. The inhibitions of Art-C and
      PBrazil on CD4 T cells were not due to direct cytotoxic effect on PBMC or
      inducing regulatory T cells differentiation. Both Art-C and PBrazil were found to
      selectively induce apoptosis in proliferating T cells. The anti-proliferative
      effect of Art-C and PBrazil were reversible and were also applied to the
      activated T cells. CONCLUSIONS: In conclusion, our results indicated that Art-C
      and PBrazil can suppress alloreactive CD4 T cell responses in vitro, suggesting
      that Art-C could be used as a potential immunosuppressant, either solely or as
      adjunct agent in treating graft versus host disease.

PMID- 21964193
TI  - Double directional adjusting estrogenic effect of naringin from Rhizoma drynariae
      (Gusuibu).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Chinese traditional medicine Rhizoma drynariae
      (Gusuibu) is widely used for clinically treating osteoporosis and bone non-union.
      Naringin and its active metabolite naringenin are the main active ingredients of
      Rhizoma drynariae total flavonoids. AIM OF THE STUDY: The purpose of this paper
      is to confirm estrogenic and anti-estrogenic activity of naringin and naringenin,
      and provide the basic data to further study for the dose-effect relationship and
      the mechanism for Rhizoma drynariae in treatment of osteoporosis and other
      estrogen deficiency-related diseases. MATERIALS AND METHODS: Naringin was
      extracted from Rhizoma drynariae. Naringin and its metabolin naringenin were
      tested estrogenic and anti-estrogenic activities through the experiment of cell
      proliferation and uterus weight gain in mice. Their estrogen-receptor binding
      abilities were tested by yeast two-hybrid experiment and nuclear receptor
      cofactor assays (RCAS) experiment, and their possible binding sites for ERbeta
      were performed by computer aided molecular docking technology. RESULTS: Naringin
      and naringenin showed significant effects on the proliferation of estrogen
      sensitive ER(+) MCF-7 cells in the absence of estrogen. Induction increased
      proliferation as the drug concentration, and the strongest proliferation appeared
      at a concentration of 8.6*10(-5)M. When estradiol (10(-10)M) and the different
      concentrations of naringin or naringenin were treated at the same time, naringin
      and naringenin could result in antagonistic effects on estradiol-induced MCF-7
      cell proliferation, but they did not significantly affect proliferation of
      estrogen-insensitive ER(-) MDA-MB-231 cells. Naringin and naringenin exhibited
      higher binding capacity to estrogen receptor beta (ERbeta) than estrogen receptor
      alpha (ERalpha) in yeast two-hybrid experiments and nuclear receptor cofactor
      assays (RCAS) experiment. Docking simulation between naringin/naringenin and
      ERbeta were performed, and the corresponding binding free energies of naringin
      receptor and naringenin-receptor docked complexes were -7.95 and -10.45kcal/mol.
      Hydrogen bonds were found between naringin and the amino acid residues Lys304 and
      His308. The oxygen atom (O11) of naringenin formed hydrogen bond to Arg346, and
      there may be hydrophobic space interactions between phenyl group (C13-C18) of
      naringenin and the amino acid residues Leu298, Met336, Met340, Phe356, Ile376 and
      Leu380. CONCLUSIONS: Naringin and naringenin revealed a double directional
      adjusting function of estrogenic and anti-estrogenic activities. Both of them
      showed estrogenic agonist activity at low concentration or lack of endogenous
      estrogen. On the other hand, they also acted as estrogenic antagonists at high
      concentrations or too much endogenous estrogen. They produced estrogenic and anti
      estrogenic effects primarily through selectively binding with ERbeta, which could
      prevent and treat osteoporosis with the mechanism of estrogenic receptor
      agitation. This paper confirmed the estrogenic and anti-estrogenic activity of
      naringin and naringenin, and further studies were still essential to study their
      dose-effect relationship and the anti-osteoporosis mechanism for Rhizoma
      drynariae in the treatment of osteoporosis and other estrogen deficiency-related
      diseases.

PMID- 21964194
TI  - Ginsenoside Rg1 inhibits vascular intimal hyperplasia in balloon-injured rat
      carotid artery by down-regulation of extracellular signal-regulated kinase 2.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Ginsenoside Rg1 (Rg1) is one of the main active
      components of Panax ginseng a well-known herbal medicine. It has been
      demonstrated to inhibit proliferation of vascular smooth muscle cells (VSMCs)
      induced by tumor necrosis factor-alphain vitro. The present study is aimed to
      examine the possible effects of Rg1 on vascular neointimal hyperplasia in balloon
      injured carotid artery of rats in vivo. MATERIALS AND METHODS: The animal model
      was established by rubbing the endothelia with a balloon catheter in the common
      carotid artery (CCA) of male Sprague Dawley rats. Then the rats were
      intraperitoneally injected with distilled water in model group and sham operation
      control, or with Rg1 4, 8 and 16mg/kg/d in other balloon injured groups. After
      consecutive 14 days, the vascular intimal hyperplasia was evidenced by
      histopathological alterations of the CCA and by changes observed in the marker of
      the proliferation of VSMCs-the proliferating cell nuclear antigen (PCNA). The
      protein expressions of PCNA and the phosphorylated extracellular signal-regulated
      kinase2 (p-ERK2) as well as mitogen-ativated protein kinase phosphatase-1 (MKP-1)
      were examined by immunohistochemistry; while the expressions of proto-oncogene (c
      fos), ERK2 and smooth muscle alpha-actin (SM alpha-actin) mRNA were analyzed by
      Real-Time RT-PCR. RESULTS: Rg1 administration could significantly ameliorate the
      histopathology of CCA and decrease the protein expression of PCNA induced by
      endothelia rubbing; and Rg1 medication also significantly decreased the
      expressions of p-ERK2 protein, ERK2 and c-fos mRNA in vessel wall, but up
      regulated the MKP-1 expression, which was reported to inactivate mitogen-ativated
      protein kinase pathway. Furthermore, Rg1 could elevate the decreased SM alpha
      actin mRNA expression induced by balloon injury. CONCLUSIONS: Rg1 can suppress
      the vascular neointimal hyperplasia induced by balloon injury, the mechanism may
      be involved in the inhibition on ERK2 signaling, and related, at least partly, to
      the increase in MKP-1 expression.

PMID- 21964196
TI  - Benefit-risk assessment of food.

PMID- 21964191
TI  - Measuring mitochondrial function in intact cardiac myocytes.
AB  - Mitochondria are involved in cellular functions that go beyond the traditional
      role of these organelles as the power plants of the cell. Mitochondria have been
      implicated in several human diseases, including cardiac dysfunction, and play a
      role in the aging process. Many aspects of our knowledge of mitochondria stem
      from studies performed on the isolated organelle. Their relative inaccessibility
      imposes experimental difficulties to study mitochondria in their natural
      environment-the cytosol of intact cells-and has hampered a comprehensive
      understanding of the plethora of mitochondrial functions. Here we review
      currently available methods to study mitochondrial function in intact
      cardiomyocytes. These methods primarily use different flavors of fluorescent dyes
      and genetically encoded fluorescent proteins in conjunction with high-resolution
      imaging techniques. We review methods to study mitochondrial morphology,
      mitochondrial membrane potential, Ca(2+) and Na(+) signaling, mitochondrial pH
      regulation, redox state and ROS production, NO signaling, oxygen consumption, ATP
      generation and the activity of the mitochondrial permeability transition pore.
      Where appropriate we complement this review on intact myocytes with seminal
      studies that were performed on isolated mitochondria, permeabilized cells, and in
      whole hearts.

PMID- 21964195
TI  - Health risk assessment of eight heavy metals in nine varieties of edible
      vegetable oils consumed in China.
AB  - Eight heavy metals, namely Cu, Zn, Fe, Mn, Cd, Ni, Pb and As, in nine varieties
      of edible vegetable oils collected from China were determined by inductively
      coupled plasma atomic emission spectrometry (ICP-AES) and graphite furnace atomic
      absorption spectrometry (GF-AAS) after microwave digestion. The accuracy of
      procedure was confirmed by certified reference materials (GBW10018 and GBW08551).
      The relative standard deviations were found below 10%. The concentrations for
      copper, zinc, iron, manganese, nickel, lead and arsenic were observed in the
      range of 0.214-0.875, 0.742-2.56, 16.2-45.3, 0.113-0.556, 0.026-0.075, 0.009
      0.018 and 0.009-0.019 MUg g(-1), respectively. Cadmium was found to be 2.64-8.43
      MUg/kg. In general, iron content was higher than other metals in the investigated
      edible vegetable oils. Comparing with safety intake levels for these heavy metals
      recommended by Institute of Medicine of the National Academies (IOM), US
      Environmental Protection Agency (US EPA) and Joint FAO/WHO Expert Committee on
      Food Additives (JECFA), the dietary intakes of the eight heavy metals from weekly
      consumption of 175 g of edible vegetable oils or daily consumption 25 g of edible
      vegetable oils for a 70 kg individual should pose no risk to human health.

PMID- 21964198
TI  - Visuomotor adaptation is impaired in patients with unilateral neglect.
AB  - Patients with unilateral neglect tend to ignore sensory information from their
      contralesional hemispace. Many symptoms of neglect can be reduced by exposing
      patients to rightward-shifting prism goggles. It was noted that the effects on
      neglect symptoms last for at least two hours. This seems surprising in light of
      the fact that the after-effect of prism adaptation in healthy subjects lasts only
      for a few trials. To account for this discrepancy Michel et al. (2003) referred
      to anecdotal observations which suggested that neglect patients show little
      awareness of prism-induced spatial errors. They argued that this lack of
      awareness might interfere with more conscious attempts to compensate for the
      prism goggles (called strategic control) and thereby enhance the effects of more
      implicit corrective mechanisms (called spatial realignment) leading to more
      pronounced and longer-lasting after-effects. We examined this hypothesis in a
      group of neglect patients, patients with right-hemispheric lesions but no neglect
      and a group of healthy age-matched controls. Our findings confirm that strategic
      control mechanisms are impaired in neglect patients. However, their after-effects
      seem neither reduced nor pathologically increased, thereby suggesting that the
      two mechanisms of prism adaptation, namely strategic control and spatial
      realignment are quite independent of each other. Furthermore we found that these
      deficits are quite specific for neglect since other patients with right
      hemisphere lesions but no neglect are not impaired in this task. We discuss the
      implications of our findings for our understanding of visual neglect, prism
      adaptation and the perception and action model.

PMID- 21964199
TI  - The nature of hemispheric specialization for linguistic and emotional prosodic
      perception: a meta-analysis of the lesion literature.
AB  - It is unclear whether there is hemispheric specialization for prosodic perception
      and, if so, what the nature of this hemispheric asymmetry is. Using the lesion
      approach, many studies have attempted to test whether there is hemispheric
      specialization for emotional and linguistic prosodic perception by examining the
      impact of left vs. right hemispheric damage on prosodic perception task
      performance. However, so far no consensus has been reached. In an attempt to find
      a consistent pattern of lateralization for prosodic perception, a meta-analysis
      was performed on 38 lesion studies (including 450 left hemisphere damaged
      patients, 534 right hemisphere damaged patients and 491 controls) of prosodic
      perception. It was found that both left and right hemispheric damage compromise
      emotional and linguistic prosodic perception task performance. Furthermore, right
      hemispheric damage degraded emotional prosodic perception more than left
      hemispheric damage (trimmed g=-0.37, 95% CI [-0.66; -0.09], N=620 patients). It
      is concluded that prosodic perception is under bihemispheric control with
      relative specialization of the right hemisphere for emotional prosodic
      perception.

PMID- 21964200
TI  - Alpha coherence predicts accuracy during a visuomotor tracking task.
AB  - It has been shown that synchrony of neuronal oscillations plays a critical role
      in effective communication between functionally distinct brain areas involving
      motor-sensory integration. However, the patterns of cortico-cortical coupling and
      their relation to behavioural success are widely unknown. Here, we analysed
      changes in cortico-cortical coherence during an unimanual visuomotor task and
      their correlation with performance. A 28-channel-EEG was attained in 27 healthy
      subjects during the tracking of an irregularly fluctuating target on a screen by
      manipulating a force sensor with the right index finger and thumb. For
      oscillatory power in the alpha (8-12 Hz) and the lower beta-band (beta1, 13-20
      Hz), we found a decrease in central and occipital areas during performance.
      Interregional coherence between contralateral frontal and central areas was
      enhanced in the alpha band. In beta1, we observed a marked increase of coherence
      in centroparietal regions of both hemispheres extending to occipital and frontal
      regions in beta2 (21-30 Hz). Most prominently, correlation analysis between alpha
      coherence and performance accuracy indicated that higher occipitocentral (i.e.
      visuomotor) coherence is associated with better visuomotor performance whereas
      high tracking error is associated with enhanced frontocentral coupling,
      suggesting additional activation of a frontoparietal control network. These
      results provide further evidence that coherent brain oscillations in alpha and
      beta bands significantly contribute to effective functional integration of visual
      and motor areas.

PMID- 21964201
TI  - Patient HC with developmental amnesia can construct future scenarios.
AB  - Deficits in recalling the past and imagining fictitious and future scenarios have
      been documented in patients with hippocampal damage and amnesia that was acquired
      in adulthood. By contrast patients with very early hippocampal damage and
      developmental amnesia are not impaired relative to control participants when
      imagining fictitious/future experiences. Recently, however, a patient (HC) with
      developmental amnesia, resulting from bilateral hippocampal atrophy, was reported
      to be impaired, thus raising a question about the true nature of event
      construction in the context of developmental amnesia. Here, we assessed HC on a
      test of imagination which explored her ability to construct fictitious events or
      personal plausible future events. Her scenario descriptions were analysed in
      detail along a range of parameters, using two different scoring methods. HC's
      performance was comparable to matched control participants on all measures
      relating to the imagination of fictitious and future scenarios. We then
      considered why she was reported as impaired in the previous study. We conclude
      that various features of the previous testing methodology may have contributed to
      the underestimation of HC's ability in that instance. Patients like HC with
      developmental amnesia may be successful at future-thinking tasks because their
      performance is not based on true visualisation or scene construction supported by
      the hippocampus, but rather on preserved world knowledge and semantic
      representations.

PMID- 21964202
TI  - Addressing potent single molecule AFM study in prediction of swelling and
      dissolution rate in polymer matrix tablets.
AB  - Our goal was to understand and thus be able to predict the swelling behavior of
      xanthan matrix tablets in media of various pH and ionic strengths using data
      obtained from single xanthan molecules and films with atomic force microscopy.
      Imaging was performed in 1-butanol using contact mode AFM in order to
      characterize single xanthan chains prepared from various solutions. Image
      analysis was used to calculate the molecular contour, persistence length, and
      radius of gyration. Nanoindentation measurements of xanthan films were carried
      out to evaluate their mechanical properties. Increasing the ionic strength of
      solutions induced reductions in chain parameters such as molecular contour,
      persistence length, and radius of gyration. Nanomechanical measurements
      demonstrated that Young's moduli of xanthan films prepared from solutions with
      higher ionic strengths are twice as large as those prepared at lower ionic
      strengths. This may help explain xanthan matrix tablets' reduced degree of
      swelling and faster dissolution rate in the presence of salts or ions. We
      successfully come to conclusion that microscopic polymer properties such as
      radius of gyration and persistence length are responsible for the macroscopic
      polymer behavior. For instance, longer persistence lengths and radius of gyration
      of xanthan's chains result in a higher degree of swelling, corresponding to
      softer polymer films, increased gel layers in matrix, and a slower release rate
      of the incorporated drug from the tablets.

PMID- 21964203
TI  - Nanoparticle agglomerates of fluticasone propionate in combination with albuterol
      sulfate as dry powder aerosols.
AB  - Particle engineering strategies remain at the forefront of aerosol research for
      localized treatment of lung diseases and represent an alternative for systemic
      drug therapy. With the hastily growing popularity and complexity of inhalation
      therapy, there is a rising demand for tailor-made inhalable drug particles
      capable of affording the most proficient delivery to the lungs and the most
      advantageous therapeutic outcomes. To address this formulation demand,
      nanoparticle agglomeration was used to develop aerosols of the asthma
      therapeutics, fluticasone or albuterol. In addition, a combination aerosol was
      formed by drying agglomerates of fluticasone nanoparticles in the presence of
      albuterol in solution. Powders of the single drug nanoparticle agglomerates or of
      the combined therapeutics possessed desirable aerodynamic properties for
      inhalation. Powders were efficiently aerosolized (~75% deposition determined by
      cascade impaction) with high fine particle fraction and rapid dissolution.
      Nanoparticle agglomeration offers a unique approach to obtain high performance
      aerosols from combinations of asthma therapeutics.

PMID- 21964204
TI  - Efficacy of chitooligosaccharides for the management of diabetes in alloxan
      induced mice: a correlative study with antihyperlipidemic and antioxidative
      activity.
AB  - The present study evaluates the effects of chitooligosaccharides (COS) for the
      management of alloxan induced diabetes in mice. For the management of the
      carbohydrate metabolism in diabetes by the COS, the amount of glucose in blood
      along with quantification of glycogen in liver were measured and noted a
      significant recovery in respect to diabetic control group. As hyperlipidemia and
      oxidative stress are the disorders of diabetes so, we have also assessed the
      serum levels of total cholesterol (TC), triglyceride (TG), low density
      lipoprotein cholesterol (LDLc), very low density lipoprotein cholesterol (VLDLc)
      and high density lipoprotein cholesterol (HDLc). For the recovery of oxidative
      stress the SOD MDA catalase in liver and GOT and GPT activities in serum were
      measured. The COS results a significant recovery in the levels of above mentioned
      biosensors of lipid profile when treated to experimentally induce diabetic mice.
      The effect of COS at the dose of 10mg/kg body weight was found to be a potent
      agent for diabetes and complication associated with this disease. The COS has no
      toxic effect in general which has been focused here by the monitoring of COS dose
      in normal healthy mice. The results of this study enlighted that the COS has
      antidiabetic, antihyperlipidemic and antioxidative activities.

PMID- 21964205
TI  - Cognitive testing of human papillomavirus vaccine survey items for parents of
      adolescent girls.
AB  - OBJECTIVE: Many studies have been conducted to understand what factors are
      associated with human papillomavirus (HPV) vaccine acceptability and completion
      of the 3-dose vaccination series, but few have examined whether people understand
      the survey items used to assess these relationships. Through a multisite
      collaborative effort, we developed and cognitively tested survey items that
      represent constructs known to affect vaccine acceptability and completion.
      MATERIALS AND METHODS: Investigators from 7 research centers in the United States
      used cognitive interviewing techniques and in-person and telephone interviews to
      test 21 items. Four rounds of testing, revising, and retesting were conducted
      among racially and ethnically diverse parents (n = 62) of girls between the ages
      of 9 and 17 years. RESULTS: The final survey contained 20 items on attitudes and
      beliefs relevant to HPV vaccine. Some parents misinterpreted statements about
      hypothetical vaccine harms as statements of fact. Others were unwilling to answer
      items about perceived disease likelihood and perceived vaccine effectiveness,
      because they said the items seemed to have a "right" answer that they did not
      know. On the basis of these and other findings from cognitive testing, we revised
      the wording of 14 questions to improve clarity and comprehension. We also revised
      instructions, response options, and item order. CONCLUSIONS: Cognitive testing of
      HPV vaccine survey items revealed important differences between intended and
      ascribed item meaning by participants. Use of the tested survey questions
      presented here may increase measurement validity and researchers' ability to
      compare findings across studies and populations. Additional testing using
      quantitative methods can help to further validate these items.

PMID- 21964206
TI  - Chronic vulvovaginitis in women older than 50 years:  analysis of a prospective
      database.
AB  - OBJECTIVE: This study aimed to examine differences in symptoms and diagnoses
      between women 50 years and younger and women older than 50 years who have chronic
      vulvovaginal complaints. METHODS: New patients of the Drexel University Vaginitis
      Center with chronic vulvovaginal complaints were eligible. Participants underwent
      a standardized medical evaluation and completed detailed questionnaires. Data
      were analyzed using the t test, chi test, and the Fisher exact test. RESULTS:
      Subjects were 469 women aged 18 to 79 years. Subjects 50 years and younger (group
      A) were more likely to complain of vaginal itching and were less likely to
      complain of burning, irritation, or soreness (p <= .05 for all). Subjects older
      than 50 years (group B) were more likely to be diagnosed with atrophic vaginitis
      (p = .000), desquamative inflammatory vaginitis (DIV; p = .001), lichen planus
      (LP; p = .000), and lichen sclerosus (p = .000). Diagnosis of LS, LP, or DIV was
      associated with increased likelihood of multiparity and decreased likelihood of a
      history of systemic estrogen use. CONCLUSIONS: Postmenopausal women are more
      likely than premenopausal women to be diagnosed with DIV, LP, or LS. Both
      childbirth and estrogen nonuse were associated with the occurrence of these
      latter 3 conditions.

PMID- 21964207
TI  - Human papillomavirus type distribution among heterosexual couples.
AB  - OBJECTIVE: To gain a better understanding of human papillomavirus (HPV)
      transmission dynamics between sexual partners, HPV-type-specific concordance was
      investigated. METHODS: Twenty-nine couples were enrolled in this cross-sectional
      study. Mean age was 30.5 years (range = 19.1-42.6 y) for men and 28.2 years
      (range = 19.4-44.5 y) for women. Samples were collected at the glans penis,
      penile shaft, and scrotum in men and at the endo/ectocervix and labia/vulva, and
      perineum in women. Samples were analyzed for the presence of HPV DNA first by
      polymerase chain reaction and then genotyped using the reverse-line blot method.
      RESULTS: Human papillomavirus prevalence for any HPV type was 75.9% among men and
      86.2% among women. Eleven men and 10 women were infected with multiple HPV types.
      At least partial type-specific concordance was observed in 66% of the couples.
      Forty-one percent of the couples had perfect concordance. In 11 couples (37.9%),
      complete discordance was observed. CONCLUSIONS: These results provide valuable
      information about HPV-type-specific concordance and demonstrate the complexity of
      transmission dynamics in heterosexual couples.

PMID- 21964208
TI  - Genital malodor in women:  a modern reappraisal.
AB  - Genital malodor is a common distressing complaint that brings a woman to her
      physician's office. Vaginal infections, primarily bacterial vaginosis and
      trichomoniasis, still remain the commonest causes and are relatively easy to
      diagnose and treat. However, in approximately one third of women who present with
      malodor, no cause is identified. Although data on the management of vaginal
      discharge are extensive, the management of genital odor beyond common vaginal
      infections remains poorly studied. This presents a frustrating situation for both
      the patient and her physician. Often, patients resort to home remedies and over
      the-counter preparations, which, while providing short-term relief for some
      women, almost never address the cause and, in some cases, can exacerbate
      symptoms. In this review, we have attempted to consolidate the known and
      documented causes of genital malodor including the nonvaginal causes and provide
      case studies that will help clinicians understand the possible settings for the
      various causes. We also provide an algorithm for the management of this symptom
      beyond vaginal infections.

PMID- 21964209
TI  - Uterine prolapse complicated with a giant cervical polyp.
AB  - OBJECTIVE: Uterine prolapse with giant cervical polyp is a rare combination.
      Although uterine prolapse is common among elderly and menopausal women, giant
      cervical polyps are commonly encountered in young reproductive-age adults. CASE
      PRESENTATION: A 55-year-old, para 7, Tanzanian woman, 7 months postmenopausal,
      presented with history of a protruding vaginal mass for 3 months. She also had a
      third-degree uterine prolapse with the cervix beyond the hymen and a huge,
      ulcerated, round mass on the anterior lip of the cervix. The mass had a large
      stalk, bled easily on touch, and measured approximately 6 * 6 cm in its largest
      diameter. The external cervical os and posterior cervical lip were identified and
      appeared normal. Transvaginal hysterectomy was performed with unremarkable
      recovery. CONCLUSIONS: Giant cervical polyp associated with uterine prolapse,
      although rare, can occur in menopausal women. Transvaginal hysterectomy as was
      done in this patient may be all that is required in benign polyps.

PMID- 21964210
TI  - Collagen expression in the pregnant human cervix is decreased with labor.
AB  - OBJECTIVE: The current study tested the hypothesis that collagen content in the
      pregnant cervix decreases with labor, using morphologically preserved specimens,
      avoiding limitations of earlier studies. Collagen abundance remote from pregnancy
      was also evaluated. MATERIALS AND METHODS: Histologic sections of postpartum
      cervix obtained from 22 cases of total hysterectomy performed immediately after
      delivery: 13 cases performed after delivery with no labor and 9 cases in which
      labor had ensued before delivery. Cervices from 10 nonpregnant uteri served as
      additional controls. Sections were stained, and quantitative histomorphometric
      assessment of relative collagen abundance was performed using computer-assisted
      image analysis. Data were assessed for differences using rank sum tests.
      Relationships between cervical collagen abundance and age, parity, ethnicity, or
      mode of delivery were also assessed. RESULTS: Quantitative assessment of collagen
      abundance in trichrome-stained cervical sections revealed significantly decreased
      cervical collagen expression in sections from pregnant uteri. Mean percent
      collagen was 73.5% +/- 3.5% (+/-SEM) in cervices from nonpregnant uteri (n = 10)
      and 21.5% +/- 2.2% in cervices from pregnant uteri (n = 22, p < .0001). Cervical
      collagen content was significantly lower (p = .04) in cervices from cases in
      which labor had ensued before delivery (mean percent collagen = 16.1% +/- 3.4%, n
      = 9) than in those in which delivery occurred with no labor (25.3% +/- 2.3%, n =
      13). No relationships between collagen expression and age, parity, ethnicity, or
      mode of delivery were observed. CONCLUSIONS: Collagen expression seems to be
      reduced in the postpartum cervix, particularly after labor has ensued.

PMID- 21964211
TI  - Conservative management of extramammary paget disease with imiquimod.
AB  - OBJECTIVE: Extramammary Paget disease is a rare cutaneous neoplasm that most
      frequently affects the vulva. Surgery remains the preferred treatment, despite
      its association with high recurrence rates. Few reports have described
      conservative treatments for vulvar Paget disease. Our aim was to evaluate the
      efficacy of conservative treatment with imiquimod. MATERIALS AND METHODS: We
      performed a retrospective analysis of 4 patients who were treated with topical
      imiquimod 5% cream. RESULTS: One patient underwent vulvectomy after imiquimod
      therapy, and 3 patients experienced extensive recurrent disease that was
      unsuitable for surgical resection and were treated successfully with imiquimod.
      CONCLUSIONS: Imiquimod is an effective therapeutic agent for the conservative
      treatment of vulvar Paget disease.

PMID- 21964212
TI  - TXNIP (VDUP-1, TBP-2): a major redox regulator commonly suppressed in cancer by
      epigenetic mechanisms.
AB  - TXNIP (also named as VDUP-1 or TBP-2) was originally isolated in HL60 cells
      treated with Vitamin D3. Subsequently, it has been identified as a major redox
      regulator and a Tumor Suppressor Gene (TSG) in various solid tumors and
      hematological malignancies. In the present review, we will first provide an
      overview of TXNIP gene and protein structures, followed by a summary of the
      studies that have demonstrated its frequent repression in human cancers and
      relevant clinical significance, as well as functional characterization in animal
      models. We will then highlight our current knowledge of TXNIP signaling and
      biological functions. Next, we will discuss the evidence that clearly have
      demonstrated that the epigenetic silencing of TXNIP in cancer through various
      molecular mechanisms. The therapeutic use of small molecular inhibitors to
      reactivate TXNIP expression for cancer treatment will also be discussed in this
      review.

PMID- 21964213
TI  - A magnesium carbonate recyclable template to synthesize micro hollow structures
      at a large scale.
AB  - A facile strategy by using magnesium carbonate as the recyclable template has
      been developed to synthesize a variety of uniform inorganic hollow structures
      whose composition, size and shape can be readily modulated to generate
      interesting structures such as TiO(2), Al(2)O(3), SiO(2), Gd(2)O(3) and NiO
      microtubes and TiO(2), SiO(2) hollow microboxes.

PMID- 21964214
TI  - Improved endothelialization and reduced thrombosis by coating a synthetic
      vascular graft with fibronectin and stem cell homing factor SDF-1alpha.
AB  - Failure of synthetic small-diameter vascular grafts is determined mainly by the
      lack of endothelial cells, as these cells inhibit thrombosis and intimal
      hyperplasia. Coating of graft material with homing factors for circulating stem
      cells has the potential to improve endogenous endothelialization of these grafts
      and to reduce graft failure. Synthetic knitted polyester grafts (6mm diameter)
      were coated with FN and SDF-1alpha before surgical interposition in the carotid
      artery of sheep. Similar uncoated vascular grafts were implanted in the
      contralateral side as internal controls. To study the early attraction of stem
      cells, grafts were implanted in a first series of nine sheep and explanted after
      1 or 3 days. In coated grafts, four times higher fractions of CD34(+) and three
      to four times higher fractions of CD117(+) cells adhering to the vessel walls
      were found than in control grafts (P<0.05). When such coated and non-coated
      grafts were implanted in 12 other sheep and explanted after 3 months, all coated
      grafts were patent, while one control graft was occluded. EcNOS staining revealed
      that FN-SDF-1alpha coating significantly increased coverage with endothelial
      cells from 27 +/- 4% of the graft to 48 +/- 4% compared with the controls
      (P=0.001). This was associated with a significant reduction of intimal
      hyperplasia (average thickness 1.03 +/- 0.09 mm in controls vs. 0.69 +/- 0.04 mm
      in coated grafts; P=0.009) and significantly less adhesion of thrombotic material
      in the middle part of the graft (P=0.029). FN-SDF-1alpha coating of synthetic
      small-caliber vascular grafts stimulated the attraction of stem cells and was
      associated with improved endothelialization and reduced intimal hyperplasia and
      thrombosis.

PMID- 21964215
TI  - Silicate bioceramics induce angiogenesis during bone regeneration.
AB  - The capacity to induce rapid vascular ingrowth during new bone formation is an
      important feature of biomaterials that are to be used for bone regeneration.
      Akermanite, a Ca-, Mg- and Si-containing bioceramic, has been demonstrated to be
      osteoinductive and to promote bone repair. This study further demonstrates the
      ability of akermanite to promote angiogenesis and investigates the mechanism of
      this behavior. The akermanite ion extract predominantly caused Si-ion-stimulated
      proliferation of human aortic endothelial cells. The Si ion in the extract was
      the most important component for the effect and the most effective concentration
      was found to be 0.6-2 MUg ml(-1). In this range of Si ion concentration, the
      stimulating effect of the ceramic ion extract was demonstrated by the morphology
      of cells at the primary, interim and late stages during in vitro angiogenesis
      using ECMatrixTM. The akermanite ion extract up-regulated the expression of genes
      encoding the receptors of proangiogenic cytokines and also increased the
      expression level of genes encoding the proangiogenic downstream cytokines, such
      as nitric oxide synthase and nitric oxide synthesis. Akermanite implanted in
      rabbit femoral condyle model promoted neovascularization after 8 and 16 weeks of
      implantation, which further confirmed its stimulation effect on angiogenesis in
      vivo. These results indicate that akermanite ceramic, an appropriate Si ion
      concentration source, could induce angiogenesis through increasing gene
      expression of proangiogenic cytokine receptors and up-regulated downstream
      signaling. To our knowledge, akermanite ceramic is the first Si-containing
      ceramic demonstrated to be capable of inducing angiogenesis during bone
      regeneration.

PMID- 21964216
TI  - Intra-abdominal adhesions: cellular mechanisms and strategies for prevention.
AB  - Postoperative intra-abdominal adhesions represent a serious clinical problem. In
      this review, we have focused on recent progress in the cellular and humoral
      mechanisms underpinning adhesion formation, and have reviewed strategies that
      interfere with these pathways as a means to prevent their occurrence. Current and
      previous English-language literature on the pathogenesis of adhesion formation
      was identified. As the burden of surgical disease in the world population
      increases, and the frequency of reoperation increases, prevention of adhesion
      formation has become a pressing goal in surgical research.

PMID- 21964217
TI  - Acquisition of fundamental laparoscopic skills: is a box really as good as a
      virtual reality trainer?
AB  - BACKGROUND: Laparoscopic surgery requires working in a three-dimensional
      environment with a two-dimensional view. Skills such as depth perception, hand to
      eye co-ordination and bimanual manipulation are crucial to its efficacy. AIM: To
      compare the efficiency of training in laparoscopic skills on a VR simulator with
      a traditional box trainer. METHOD: Twenty medical students were recruited. An
      initial training session on the relevant anatomy and steps of a laparoscopic
      cholecystectomy was given. Baseline skills were recorded using a pre-training
      laparoscopic cholecystectomy on the VR trainer. Parameters measured were: (1)
      total time taken (mins); (2) number of movements right and left instrument; (3)
      path length (cms) of right and left instrument was recorded. Ten students trained
      on a VR simulator, and ten on a box trainer, for three hours each. The box
      trainer group exercises were based on the Royal College of Surgeons core
      laparoscopic skills course, and the VR trainer exercises were based on the
      Simbionix LapMentor basic skills tasks. Following this both groups were
      reassessed by a laparoscopic cholecystectomy on the VR trainer. RESULTS: Both
      groups showed improvement in all measured parameters. A student T-test at 95%
      confidence interval showed no statistically significant difference between the
      two groups pre and post training. CONCLUSION: Both the VR and box trainer are
      effective in the acquisition of laparoscopic skills.

PMID- 21964218
TI  - [Effects and adequacy of high-fidelity simulation-based training for obstetrical
      nursing].
AB  - PURPOSE: Clinical training for nursing students is limited to rudimentary skills
      to avoid potential risks. Simulation-Based Training (SBT) can overcome the
      shortcomings of clinical training. We evaluated the educational effect of SBT for
      obstetrical nursing students using high-fidelity simulation courses. METHODS: We
      developed a simulation program for obstetrical nursing students to practice
      nursing skills that are necessary to provide quality care. The program consisted
      of four sessions. 1st: An orientation and a preliminary test. 2nd: Learning core
      skills required in obstetrical nursing. 3rd: Testing each student with scenario.
      4th: Providing a debriefing session. At the beginning of the program, students
      were surveyed about their self-confidence in obstetrical nursing care, and at the
      end of the program, they were surveyed about the adequacy of SBT as well as self
      confidence. RESULTS: Students' self-confidence showed a significant difference
      before and after simulation. Mean adequacy of SBT was 7.15+/-1.35 (out of 10).
      Most students became more interested in Women's Health Nursing after SBT.
      CONCLUSION: The results from evaluating the effects of simulation-based
      obstetrical nursing training show that SBT provides invaluable clinical
      experience for obstetrical nursing students by overcoming the lack of actual
      clinical involvement in clinical training programs.

PMID- 21964219
TI  - [Infants' temperament and health problems according to maternal postpartum
      depression].
AB  - PURPOSE: Mothers' postpartum depression is a worldwide health concern that
      produces compromising effects on their infants. This study was conducted to
      compare the infants' temperament and health problems according to the presence of
      maternal postpartum depression. METHODS: Data were collected from May to October
      in 2009. The sample was 137 mothers at one month postpartum. The Edinburgh
      Postpartum Depression Scale (EPDS) was used to assess depressive symptoms.
      RESULTS: At one month postpartum, 22.6% of mothers were classified as having
      postpartum depression. Infants of depressed mothers were more frequently
      classified as difficult temperament infants. They showed lower scores on the
      amenability, rhythmicity and persistency and higher scores on activity in
      temperament. Also, infants of depressed mothers reported more infant health
      problems at one months. Maternal depression showed significant negative
      correlations with family functioning, social support and marital satisfaction.
      CONCLUSION: Study findings show that postpartum maternal depression is associated
      with infants' temperament and health, and thus screening and early interventions
      for postpartum depression would promote the health of both the mother and infant.

PMID- 21964220
TI  - [Effects of breast massage on breast pain, breast-milk sodium, and newborn
      suckling in early postpartum mothers].
AB  - PURPOSE: In this study the effects of breast massage on breast pain, breast-milk
      sodium, and newborn suckling in early postpartum mothers were investigated.
      METHODS: The design was a non-synchronized nonequivalent control group pretest
      posttest design. Sixty postpartum mothers who were admitted to a postpartum care
      center and had problems with breastfeeding were recruited. Of these mothers, 44
      were assigned to the intervention group and received two 30-minute breast
      massages within 10 days of postpartum period. The others were assigned control
      group and received only routine care. Breast pain was measured using a numeric
      pain scale and number of times newborns suckled was observed throughout
      breastfeeding. Breast milk was self-collected to evaluate breast-milk sodium.
      RESULTS: Mean age of postpartum mothers was 30 years old. Compared to the control
      group, women in the intervention group reported significant decreases in breast
      pain (p<.001), increases in number of times newborns suckled after the first and
      second massage (p<.001), and a decrease in breast-milk sodium after the first
      massage (p=.034). CONCLUSION: Breast massage may have effects on relieving breast
      pain, decreasing breast-milk sodium, and improving newborn suckling. Breast
      massage can be used to solve breast problems. Further research is needed to
      validate our findings.

PMID- 21964221
TI  - [An explanatory model for sleep disorders in people with cancer].
AB  - PURPOSE: The aim of this study was to develop and test an explanatory model for
      sleep disorders in people with cancer. A hypothetical model was constructed on
      the basis of a review of previous studies, literature, and sleep models, and 10
      latent variables were used to construct a hypothetical model. METHODS: Data were
      collected from April 19 to June 25, 2010, using self-report questionnaires. The
      sample was 291 outpatients with cancer who visited the oncology cancer center at
      a university hospital. Collected data were analyzed using SPSS Win 15.0 program
      for descriptive statistics and correlation analysis and AMOS 7.0 program for
      covariance structural analysis. RESULTS: It appeared that overall fit index was
      good as chi(2)/df=1.162, GFI=.969, AGFI=.944, SRMR=.052, NFI=.881, NNFI=.969,
      CFI=.980, RMSEA=.024, CN=337 in the modified model. The explanatory power of this
      model for sleep disorders in people with cancer was 62%. Further, sleep disorders
      were influenced directly by cancer symptom experience, dysfunctional beliefs and
      attitudes about sleep, and past sleep pattern. CONCLUSION: Findings suggest that
      nurses should assess past sleep pattern and consider the development of a
      comprehensive nursing intervention program to minimize the cancer symptom
      experience, dysfunctional beliefs and attitudes about sleep, and thus, reduce
      sleep disorders in people with cancer.

PMID- 21964222
TI  - [Effectiveness of PLISSIT model sexual program on female sexual function for
      women with gynecologic cancer].
AB  - PURPOSE: The purpose of this study was to evaluate the effectiveness of the
      Permission, Limited Information, Specific Suggestions, Intensive Therapy
      (PLISSIT) model sexual program on female sexual function for women with
      gynecologic cancer. METHODS: The integrative 6-hr (two hours per session) program
      reflecting physical and psychosocial aspects of women's sexuality was developed
      based on Annon's PLISSIT model. Participants were 61 women with cervical,
      ovarian, or endometrial cancer. Of them, 29 were assigned to the experimental
      group and 32 to the control group. The women completed the Female Sexual Function
      Index (FSFI) including sexual desire, arousal, lubrication, orgasm, satisfaction,
      and pain. Independent t-test and repeated measured ANOVA were used to test the
      effectiveness of the program. RESULTS: Significant group differences were found
      on FSFI sub-domain scores including sexual desire, arousal, lubrication, orgasm,
      and satisfaction but not pain. Significant time differences were found on all
      domains except for pain in the experimental group repeated measured ANOVA.
      CONCLUSION: The results indicate that the three-week PLISSIT model sexual program
      is effective in increasing sexual function for women with gynecologic cancer.
      Nurses may contribute to improving women's sexual function by utilizing the
      program. Strategies to relieve sexual pain need to be considered for greater
      effectiveness of the program.

PMID- 21964223
TI  - [Prediction model of quality of life in elderly based on ICF model].
AB  - PURPOSE: The purpose of this study was to identify from the International
      Classification of Functioning model, factors influencing quality of life in
      elderly persons and to describe the concrete pathway of influence and the power
      of each variable. METHODS: The sample included 334 elders who lived in 5
      districts of D Metropolitan City. A structured questionnaire was used and the
      collected data were analyzed for fitness, using the AMOS 18.0 program. RESULTS:
      This model was concise and extensive in predicting the quality of life of elders.
      The research verified the factors influencing quality of life for elders as
      direct factors such as activity of daily living (ADL) (beta=.13, t=2.47), leisure
      activity (beta=.55, t=5.04), social disengagement (beta=-.25, t=-2.25), and
      depression (beta=-.62, t=-10.86). Indirect factors including economic status
      (gamma=.17, p=.009), type of residence (gamma=.19, p=.004), ADL (gamma=.12,
      p=.027) were important factors in predicting quality of life for elders. These
      variables explained 75.6% of variance in the prediction model. CONCLUSION: The
      findings indicate a need for the nursing scientific community to develop
      intervention programs considering these variables to improve the quality of life
      for elders.

PMID- 21964224
TI  - [A predictive model on self care behavior for patients with type 2 diabetes:
      based on self-determination theory].
AB  - PURPOSE: The study was conducted to develop and test a hypothetical model which
      explains self-care behavior in patients with type 2 diabetes was established
      based on the Self-Determination Theory. METHODS: The participants were 218
      patients with type 2 diabetes mellitus enrolled in an outpatient clinic of one
      endocrine center in Korea. The data were collected using questionnaires from
      April 5 through May 7, 2010. The descriptive and correlation statistics were
      analyzed using the SPSS/WIN 15.0 and the structural equation modeling procedure
      was performed using the AMOS 7.0 program. RESULTS: The results of this study
      showed that competence and autonomous motivation were the strong factors
      influencing self-care behavior in patients in this sample. Support from health
      provider for autonomy was a significant indirect factor on self-care behavior.
      These factors explained 64.9% of variance in the participants' self care
      behavior. The proposed model was concise and extensive in predicting self-care
      behavior of the participants. CONCLUSION: Findings may provide useful assistance
      in developing effective nursing interventions for maintaining and promoting self
      care behavior in patients with type 2 diabetes.

PMID- 21964225
TI  - [Analysis of cost and efficiency of a medical nursing unit using time-driven
      activity-based costing].
AB  - PURPOSE: Time-driven activity-based costing was applied to analyze the nursing
      activity cost and efficiency of a medical unit. METHODS: Data were collected at a
      medical unit of a general hospital. Nursing activities were measured using a
      nursing activities inventory and classified as 6 domains using Easley-Storfjell
      Instrument. Descriptive statistics were used to identify general characteristics
      of the unit, nursing activities and activity time, and stochastic frontier model
      was adopted to estimate true activity time. RESULTS: The average efficiency of
      the medical unit using theoretical resource capacity was 77%, however the
      efficiency using practical resource capacity was 96%. According to these results,
      the portion of non-added value time was estimated 23% and 4% each. The sums of
      total nursing activity costs were estimated 109,860,977 won in traditional
      activity-based costing and 84,427,126 won in time-driven activity-based costing.
      The difference in the two cost calculating methods was 25,433,851 won.
      CONCLUSION: These results indicate that the time-driven activity-based costing
      provides useful and more realistic information about the efficiency of unit
      operation compared to traditional activity-based costing. So time-driven activity
      based costing is recommended as a performance evaluation framework for nursing
      departments based on cost management.

PMID- 21964226
TI  - [Development of an evaluation instrument for service quality in nursing homes].
AB  - PURPOSE: The purposes of this study were to identify the factors influencing
      service quality in nursing homes, and to develop an evaluation instrument for
      service quality. METHODS: A three-phase process was employed for the study. 1)
      The important factors to evaluate the service quality in nursing homes were
      identified through a literature review, panel discussion and focus group
      interview, 2) the evaluation instrument was developed, and 3) validity and
      reliability of the study instrument were tested by factor analysis, Pearson
      correlation coefficient, Cronbach's alpha and Cohen's Kappa. RESULTS: Factor
      analysis showed that the factors influencing service quality in nursing homes
      were healthcare, diet/assistance, therapy, environment and staff. To improve
      objectivity of the instrument, quantitative as well as qualitative evaluation
      approaches were adopted. The study instrument was developed with 30 items and
      showed acceptable construct validity. The criterion-related validity was a
      Pearson correlation coefficient of .85 in 151 care facilities. The internal
      consistency was Cronbach's alpha=.95. CONCLUSION: The instrument has acceptable
      validity and a high degree of reliability. Staff in nursing homes can
      continuously improve and manage their services using the results of the
      evaluation instrument.

PMID- 21964227
TI  - [Effects of nitric oxide synthase inhibitor on hindlimb muscles in rats with
      neuropathic pain induced by unilateral peripheral nerve injury].
AB  - PURPOSE: The purpose of this study was to examine effects of nitric oxide
      synthase (NOS) inhibitor on muscle weight and myofibrillar protein content of
      affected and unaffected hindlimb muscles in rats with neuropathic pain induced by
      unilateral peripheral nerve injury. METHODS: Neuropathic pain was induced by
      ligation and cutting of the left L5 spinal nerve. Adult male Sprague-Dawley rats
      were randomly assigned to one of two groups: The NOSI group (n=19) had NOS
      inhibitor (L-NAME) injections daily for 14 days, and the Vehicle group (n=20) had
      vehicle injections daily for 14 days. Withdrawal threshold, body weight, food
      intake and activity were measured every day. At 15 days all rats were
      anesthetized and soleus, plantaris and gastrocnemius muscles were dissected from
      hindlimbs. Muscle weight and myofibrillar protein content of the dissected
      muscles were determined. RESULTS: The NOSI group showed significant increases as
      compared to the Vehicle group for body weight at 15 days, muscle weight and
      myofibrillar protein content of the unaffected soleus and gastrocnemius. The NOSI
      group demonstrated a higher pain threshold than the vehicle group. CONCLUSION:
      NOSI for 14 days attenuates unaffected soleus and gastrocnemius muscle atrophy in
      neuropathic pain model.

PMID- 21964228
TI  - [Effects of multisensory stimulation using familiarity: persons with dementia in
      long-term care facility in Korea].
AB  - PURPOSE: The purpose of the study was to examine the effects of multisensory
      stimulation (MSS) using familiarity on persons with dementia (PWDs) residing in
      nursing homes in Korea. METHODS: A nonequivalent control group with pre and
      posttests was used. Fifty one PWDs were included if they: 1) were over 65 yr old,
      2) were diagnosed with dementia, 3) had no visual or speech impairments, 4) were
      able to communicate, and 5) had spent more than one month in a nursing home. The
      experimental group (n=25) received a 55 min MSS program twice a week for 10
      weeks. The outcome variables included were cognition, activities of daily living,
      grip strength, depression, wandering, and aggressive behaviors. Repeated ANOVA
      was used for data analysis. RESULTS: There were no significant differences in
      demographics or the main variables at pretest. Cognition, depression, wandering,
      and aggressive behaviors were significant over time between the two groups. Grip
      strength was only significant when accounting for interaction between group and
      time. CONCLUSION: An intervention of MSS using familiarity was marginally
      effective in improving cognition, depression, wandering, and aggression. Future
      study is suggested with a larger sample and longer treatment to retest the
      effects of MSS.

PMID- 21964229
TI  - [Attitudes of adolescents toward suicide: Q-methodological approach].
AB  - PURPOSE: The purpose of this study was to identify attitudes of adolescents
      toward suicide. METHODS: Q-methodology which provides a method of analyzing the
      subjectivity of each item was used. Thirty middle and high school students
      classified 37 selected statements into a normal distribution using a 9 point
      scale. Collected data were analyzed using the Quanl PC Program. RESULTS: Three
      types of attitudes toward suicide were identified. The first type (opposing
      suicide-moral minded) showed an attitude of opposing suicide and thinking that
      suicide is a sin. The second type (understanding-empathizing suicidal person)
      showed an attitude of understanding the situation of the adolescents who has
      suicidal ideation and empathizing with them. The third type (ambivalent attitude)
      showed an attitude of understanding the suicidal person but, at the same time,
      opposing suicide. CONCLUSION: Results of the study indicate that different
      approaches to suicide prevention programs should be developed based on the three
      types of suicide attitudes among adolescents.

PMID- 21964230
TI  - [Factors influencing depression among middle-school girls].
AB  - PURPOSE: The purpose of this study was to investigate the prevalence of
      depression among school girls in Korea and identify factors influencing the
      tendency to depression. METHODS: A self-report survey was conducted with South
      Korean middle schoolgirls who were in the 8th and 9th grades. Four hundred and
      one schoolgirls were included in the study. The instruments utilized in this
      study were the Center for Epidemiologic Studies - Depression Scale and Social
      Problem Solving Inventory-Revised. Data were analyzed using descriptive
      statistics, Pearson correlation and multiple logistic regression with SPSS WIN
      14.0 program. RESULTS: The average depression score of the participants was
      20.68, which indicates moderate levels of depression. About 35% of the
      schoolgirls in this study reported a tendency to depression. Significant
      predictors for depression were 'decreased problem-solving abilities', 'no family
      members with whom they can discuss their concern', 'decreased satisfaction in
      relationship with friends', and 'increased negative self-perception of body
      image'. CONCLUSION: The study findings suggest that schoolgirls require special
      concern regarding the risk of developing depression. Regular depression screening
      could be beneficial for early detection of depression in schoolgirls and
      enhancing problem-solving ability could be considered as an effective strategy to
      reduce the risk of depression among schoolgirls.

PMID- 21964231
TI  - [Monitoring the use of health-related quality of life measurements in Korean
      studies of patients with diabetes].
AB  - PURPOSE: The purpose of this study was to monitor the use of health-related
      quality of life (HRQOL) instruments in Korean studies of patients with diabetes.
      METHODS: Of 86 Korean studies initially identified, 17 studies met the inclusion
      criteria. For each study, a description of the instrument and its psychometric
      properties were monitored by the Instrument Review Criteria of the Scientific
      Advisory Committee. These criteria include conceptual definition, attributes,
      taxonomy, reliability, validity, responsiveness, administrative mode, and
      language adaptations. RESULTS: Five generic and one diabetes specific type
      questionnaires were identified from the 17 studies. Of those studies, conceptual
      definitions with the attributes of multi-dimension and subjectiveness were
      provided for 11 studies (71%). In the analysis of conceptual taxonomy, only 6
      studies were classified as HRQOL, while other studies were done as QOL or health
      status. In monitoring of psychometric properties, reliability, validity, and
      responsiveness were reported for 88.2%, 64.7%, and 29.4%, respectively. One
      generic instrument was developed with a Korean population, while the other
      instruments were developed for Western countries. However, language adaptations
      were performed for only a few of the instruments. CONCLUSION: The psychometric
      properties including responsiveness of most instruments warrants further
      research, and the development of diabetes-specific HRQOL measurements should be
      sought to facilitate intervention outcomes across Korean studies of patients with
      diabetes.

PMID- 21964232
TI  - [Hospital workers' experience with hospital evaluation program: a focus group
      study].
AB  - PURPOSE: The purpose of the study was to understand and describe the hospital
      workers' experience related to the hospital evaluation program implemented in
      Korea between 2004 and 2009. METHODS: During 2010, data were collected using
      focus group interviews. Four focus group interviews were held with a total of 28
      hospital workers participating. All interviews were recorded and transcribed as
      they were spoken, and data were analyzed using qualitative content analysis.
      RESULTS: Nine themes emerged from the analysis: 1) Positive change in the
      necessity of the evaluation; 2) Improvement in the hospital system, facilities,
      and human resources; 3) Unity through cooperation among departments; 4) Nursing
      work overload; 5) Lack of physicians' awareness and responsibilities; 6) Unfair
      and unrealistic evaluation items; 7) Lack of credibility of the outcome; 8)
      Shifting responsibility for negative outcomes to the workers; 9) Lack of
      pragmatic utility. CONCLUSION: The results of the study demonstrate that the
      hospital evaluation program played a key role in improving some work environments
      and communication among departments. At the same time, they show various negative
      themes resulting from the context of very authoritarian hospital systems and a
      connection-oriented society in Korea.

PMID- 21964233
TI  - Successful intraoperative retrieval of dislocated femoral trial head during total
      hip arthroplasty.
AB  - Since the advent of modular hip prostheses in the early 1970s, dissociation of
      the femoral trial head and migration into the deep tissue space of the pelvis are
      rarely reported complications of total hip arthroplasty. Several case reports
      have described this complication, but the actual incidence is unknown and likely
      underreported. Two cases are presented here using a new technique to retrieve a
      trial femoral head from within the pelvis without use of an extensile approach,
      laparoscopic retrieval, or secondary incisions.

PMID- 21964234
TI  - Patellofemoral arthroplasty: 7-year mean follow-up.
AB  - Patellofemoral arthroplasty has had renewed interest with the purpose of this
      study to evaluate its outcomes. Between 2001 and 2006, 43 were performed in 37
      patients who had a mean follow-up of 7 years (range, 4-8 years). Patient outcomes
      were determined using Knee Society objective and function scores, revision rates,
      and complication rates. The 5-year Kaplan-Meier survivorship was 95%. Knee
      Society objective scores improved from a mean of 64 points (range, 57-68 points)
      to 87 points (range, 50-100 points), and functional scores improved from a mean
      of 48 points (range, 45-50 points) to 82 points (range, 20-100 points). This
      study shows maintained successful clinical and radiographic results at mean 7
      year follow-up for patellofemoral arthroplasty.

PMID- 21964235
TI  - High complication rate in locking plate fixation of lower periprosthetic distal
      femur fractures in patients with total knee arthroplasties.
AB  - Fixation of the distal portion of the femur in patients with total knee
      arthroplasties can be challenging. Locking plates have emerged as a promising
      treatment. Twenty-seven patients with periprosthetic distal femur fractures after
      total knee arthroplasties were treated using a contralateral reverse distal
      femoral locking plate. The average time for union and weight-bearing was 4.5 +/-
      2.7 months. The union rate was 89%. Thirty-seven percent experienced
      complications, with 2 delayed unions (7.4%), 1 nonunion (3.7%), and 7 fixation
      failures (26%). Alteration in blood supply and biomechanics as well as poor
      existing bone quality and minimal distal femur bone stock may contribute to
      treatment difficulties.

PMID- 21964236
TI  - IL-7 concentration is increased in nonagenarians but is not associated with
      markers of T cell immunosenescence.
AB  - Interleukin-7 is a homeostatic cytokine that contributes to the maintenance of
      the T cell pool. It also has proinflammatory effects and is involved in the
      pathogenesis of autoimmune diseases. Due to its homeostatic effects, IL-7 has
      been proposed as a potential rejuvenation factor for the elderly immune system.
      We analyzed the correlation of plasma IL-7 concentrations and the proportions of
      different T cell populations in nonagenarians (n=163) participating in the
      Vitality 90+ study. Young individuals (n=35, aged 19-30years) were used as
      controls. The numbers of CD3+, CD14+, CD4+ and CD8+ cells and the expression of
      the CD28 costimulatory molecule on CD4+ and CD8+ lymphocyte subsets were analyzed
      using flow cytometry. The plasma IL-7 levels were significantly higher in the
      nonagenarians compared to the controls (7.86 vs. 5.74pg/ml, p=0.004). In the
      nonagenarians, plasma IL-7 levels correlated inversely with the proportion of
      CD3+ T cells and directly with the proportion of CD14+ monocytes and plasma C
      reactive protein. No correlation was observed between plasma IL-7 levels and the
      proportions of CD4+CD28- or CD8+CD28- subsets. These results suggest that the IL
      7 levels in nonagenarians do not have an inhibitory effect on the development of
      immunosenescence; rather they are associated with increased inflammation.

PMID- 21964237
TI  - Neural systems analysis of decision making during goal-directed navigation.
AB  - The ability to make adaptive decisions during goal-directed navigation is a
      fundamental and highly evolved behavior that requires continual coordination of
      perceptions, learning and memory processes, and the planning of behaviors. Here,
      a neurobiological account for such coordination is provided by integrating
      current literatures on spatial context analysis and decision-making. This
      integration includes discussions of our current understanding of the role of the
      hippocampal system in experience-dependent navigation, how hippocampal
      information comes to impact midbrain and striatal decision making systems, and
      finally the role of the striatum in the implementation of behaviors based on
      recent decisions. These discussions extend across cellular to neural systems
      levels of analysis. Not only are key findings described, but also fundamental
      organizing principles within and across neural systems, as well as between neural
      systems functions and behavior, are emphasized. It is suggested that studying
      decision making during goal-directed navigation is a powerful model for studying
      interactive brain systems and their mediation of complex behaviors.

PMID- 21964238
TI  - The neutralizing human recombinant antibodies to pathogenic Orthopoxviruses
      derived from a phage display immune library.
AB  - A panel of recombinant human antibodies to orthopoxviruses was isolated from a
      combinatorial phage display library of human scFv antibodies constructed from the
      Vh and Vl genes cloned from the peripheral blood lymphocytes of Vaccinia virus
      (VACV) immune donors. Plaque-reduction neutralization tests showed that seven
      selected phage-displaying scFv antibodies (pdAbs) neutralized both CPXV and VACV,
      and five of them neutralized Monkeypox virus (MPXV). Western blot analysis of
      VACV and CPXV proteins demonstrated that seven neutralizing antibodies recognized
      a 35 kDa protein. To identify this target protein, we produced a recombinant J3L
      protein of CPXV and showed that all the selected neutralizing antibodies
      recognized this protein. Neutralizing pdAb b9 was converted into fully human mAb
      b9 (fh b9), and scFv b9 displayed high binding affinities (K(d) of 0.7 and 3.2
      nM). The fh b9 reduced VACV plaque formation in a dose-dependent manner.

PMID- 21964239
TI  - Studies of the spin-Hamiltonian parameters and defect structures for the
      tetragonal and cubic Yb3+ centers in AgCl crystal.
AB  - The spin-Hamiltonian parameters, g factors and hyperfine structure constants, for
      the tetragonal and cubic Yb(3+) centers in AgCl crystal are calculated from the
      complete diagonalization (of energy matrix) method. The calculations are based on
      the defect models that the tetragonal Yb(3+) center is formed by the
      substitutional Yb(3+) associated with two nearest Ag(+) vacancy (V(Ag)) along
      <001> and <001-> axes (i.e., C(4) axis) owing to charge compensation and in cubic
      Yb(3+) center the two compensators V(Ag) are remote. From the calculations, the
      spin-Hamiltonian parameters of both Yb(3+) centers in AgCl are explained
      reasonably, the signs of hyperfine structure constants A(i)((171)Yb(3+)) and
      A(i)((173)Yb(3+)) are suggested, the above defect models of both Yb(3+) centers
      are confirmed and their defect structures are determined.

PMID- 21964240
TI  - Structural analysis, vibrational spectra and coordinated normal of 2R-(-)-6
      hydroxytremetone.
AB  - We have studied and characterized the structural and vibrational properties of 2R
      (-)-6-hydroxytremetone, isolated from Xenophyllum poposum (Phil.) by infrared and
      Raman spectroscopy in the solid phase. The density functional theory (DFT) method
      together with Pople's basis set show that two stable molecules for the compound
      have been theoretically determined in the gas phase and that both conformations
      are present in the solid phase, as was experimentally observed. The harmonic
      vibrational wavenumbers for the optimized geometry were calculated at B3LYP/6
      31G*and B3LYP/6-311++G** levels. For a complete assignment of the vibrational
      spectra, DFT calculations were combined with Pulay's Scaled Quantum Mechanics
      Force Field (SQMFF) methodology in order to fit the theoretical wavenumber values
      to the experimental ones. Then, a complete assignment of all the observed bands
      in the infrared spectrum for the compound was performed. The natural bond orbital
      (NBO) study reveals the characteristics of the electronic delocalization of the
      two structures, while the corresponding topological properties of electronic
      charge density are analyzed by employing Bader's Atoms in the Molecules theory
      (AIM).

PMID- 21964241
TI  - UV-Vis, fluorescence and NMR spectroscopic investigations on inclusion properties
      of a designed tetrahomocalix[8]arene with fullerenes C60 and C70 in solution.
AB  - The present article reports the spectroscopic investigations on non-covalent
      interaction of fullerenes C(60) and C(70) with a macrocyclic receptor molecule,
      namely, 1,3,5,7-tetrahomo-p-tert-butylcalix[8]arene (1) in toluene. Jobs method
      of continuous variation reveals 1:1 stoichiometry for the fullerene complexes of
      1. The most fascinating feature of the present study is that 1 binds selectively
      C(60) compared to C(70) as obtained from binding constant (K) data of C(60)-1
      (K(C60-1)) and C(70)-1 (K(C70-1)) complexes which are enumerated to be 265,000
      dm(3) mol(-1) and 63,43 dm(3) mol(-1), respectively, and selectivity in binding
      (K(C60-1)/K(C70-1)) is estimated to be 4.18 as obtained from UV-Vis study. Steady
      state fluorescence studies reveal quenching of fluorescence of 1 in presence of
      fullerenes and the K value of the C(60)-1 and C(70)-1 complexes are estimated to
      be 80,760 and 68,780 dm(3) mol(-1), respectively, with selectivity in binding
      (K(C60-1)/K(C70-1)) ~1.18. (1)H NMR analysis provides very good support in favor
      of strong binding between C(60) and 1. The high value of K value for C(60)-1
      complex indicates that 1 forms an inclusion complex with C(60).

PMID- 21964242
TI  - Oral cancer awareness and knowledge among dental patients in South India.
AB  - AIM: To assess the 1) levels of awareness and knowledge about risk factors and
      early signs of oral cancer among dental patients visiting dental hospital in
      Hyderabad city, South India 2) and to correlate the knowledge levels according to
      age, gender and education levels. METHODS: The survey comprised of 16-item
      questionnaire which was distributed to patients attending Panineeya Institute of
      Dental Sciences, Hyderabad. Data was collected and statistically analysis was
      done using SPSS software (12.0 version). p<0.05 was considered statistically
      significant. RESULTS: 2045 participants completed the questionnaire (response
      rate - 97. 9%). The reliability of the questionnaire as calculated by Cronbach's
      alpha was 0.75. Mean age of the study population was 37.9 years. 60.2% of the
      respondents had heard about oral cancer. When knowledge towards risk factors of
      oral cancer was taken into consideration along with variables, significant
      differences were seen only in gender with female having better knowledge
      (p=0.02). No significant difference was noted among the age group and varying
      education levels. However, knowledge about early signs of oral cancer revealed a
      highly significant difference with the level of education (p=0.000). CONCLUSION:
      The awareness levels and knowledge about risk factors and early signs of oral
      cancer in this cross-section of Indian dental patients were satisfactory.

PMID- 21964243
TI  - Epigallocatechin gallate (EGCG) inhibits type II phosphatidylinositol 4-kinases:
      a key component in pathways of phosphoinositide turnover.
AB  - Type II phosphatidylinositol (PtdIns) 4-kinases produce PtdIns 4-phosphate, an
      early key signaling molecule in phosphatidylinositol cycle, which is
      indispensable for T cell activation. Type II PtdIns 4-kinase alpha and beta have
      similar biochemical properties. To distinguish these isoforms Epigallocatechin
      gallate (EGCG) has been evaluated as a specific inhibitor. EGCG is the major
      active catechin in green tea having anti-inflammatory, antiatherogenic and cancer
      chemopreventive properties. The precise mechanism of actions and molecular
      targets of EGCG in early signaling cascades are not well understood. In the
      present study, we have shown that EGCG inhibits type II PtdIns 4-kinases (alpha
      and beta isoforms) and PtdIns 3-kinase activity in vitro. EGCG directly bind to
      both alpha and beta isoforms of type II PtdIns 4-kinases with a Kd of 2.62 MUM
      and 1.02 MUM, respectively. Type II PtdIns 4-kinase-EGCG complex have different
      binding pattern at its excited state. Both isoforms showed significant change in
      helicity upon binding with EGCG. EGCG modulates its effect by interacting with
      ATP binding pocket; the residues likely to be involved in EGCG binding were
      predicted by Autodock. Our findings suggest that EGCG inhibits two isoforms and
      could be a key to regulate T cell activation.

PMID- 21964244
TI  - Crystal structure of the passenger domain of the Escherichia coli autotransporter
      EspP.
AB  - Autotransporters represent a large superfamily of known and putative virulence
      factors produced by Gram-negative bacteria. They consist of an N-terminal
      "passenger domain" responsible for the specific effector functions of the
      molecule and a C-terminal "beta-domain" responsible for translocation of the
      passenger across the bacterial outer membrane. Here, we present the 2.5-A crystal
      structure of the passenger domain of the extracellular serine protease EspP,
      produced by the pathogen Escherichia coli O157:H7 and a member of the serine
      protease autotransporters of Enterobacteriaceae (SPATEs). Like the previously
      structurally characterized SPATE passenger domains, the EspP passenger domain
      contains an extended right-handed parallel beta-helix preceded by an N-terminal
      globular domain housing the catalytic function of the protease. Of note, however,
      is the absence of a second globular domain protruding from this beta-helix. We
      describe the structure of the EspP passenger domain in the context of previous
      results and provide an alternative hypothesis for the function of the beta-helix
      within SPATEs.

PMID- 21964246
TI  - Amperometric detection of cholesterol using an indirect electrochemical oxidation
      method.
AB  - The indirect electrochemical oxidation method using bromine species in an organic
      media for measuring cholesterol was developed. The electrochemical behaviors of
      cholesterol were examined by cyclic voltammetry in a potential range of -0.5 to
      2.0V (vs. Ag/AgCl/saturated KCl). The polarization curve of the steady-state
      current in the applied potential range of 0-2.0V is reported. The obtained
      kinetic parameters for the catalytic oxidation of cholesterol support the
      assumption that positive bromine species can be generated from bromine by
      undergoing two consecutive electrochemical oxidation steps. The positive bromine
      acts both as electron mediators and as electrocatalysts. Amperometric detection
      with an anodic current was investigated, and the calibration curve exhibited a
      linear relationship between the steady-state current and the concentration of
      cholesterol in the range of 30-200 MUM, from which the sensitivity was calculated
      to be about 0.2 MUA/cm2/MUM. Moreover, the amperometric current followed
      Michaelis-Menten's enzymatic model for cholesterol concentrations in the range of
      30 MUM to 5mM, which can be applied for cholesterol rapid detection in processed
      foods.

PMID- 21964248
TI  - The role of the asymptotic dynamics in the design of FPGA-based hardware
      implementations of gIF-type neural networks.
AB  - This paper presents a numerical analysis of the role of asymptotic dynamics in
      the design of hardware-based implementations of the generalised integrate-and
      fire (gIF) neuron models. These proposed implementations are based on extensions
      of the discrete-time spiking neuron model, which was introduced by Soula et al.,
      and have been implemented on Field Programmable Gate Array (FPGA) devices using
      fixed-point arithmetic. Mathematical studies conducted by Cessac have evidenced
      the existence of three main regimes (neural death, periodic and chaotic regimes)
      in the activity of such neuron models. These activity regimes are characterised
      in hardware by considering a precision analysis in the design of an architecture
      for an FPGA-based implementation. The proposed approach, although based on gIF
      neuron models and FPGA hardware, can be extended to more complex neuron models as
      well as to different in silico implementations.

PMID- 21964245
TI  - Palatogenesis: engineering, pathways and pathologies.
AB  - Cleft palate represents the second most common birth defect and carries
      substantial physiologic and social challenges for affected patients, as they
      often require multiple surgical interventions during their lifetime. A number of
      genes have been identified to be associated with the cleft palate phenotype, but
      etiology in the majority of cases remains elusive. In order to better understand
      cleft palate and both surgical and potential tissue engineering approaches for
      repair, we have performed an in-depth literature review into cleft palate
      development in humans and mice, as well as into molecular pathways underlying
      these pathologic developments. We summarize the multitude of pathways underlying
      cleft palate development, with the transforming growth factor beta superfamily
      being the most commonly studied. Furthermore, while the majority of cleft palate
      studies are performed using a mouse model, studies focusing on tissue engineering
      have also focused heavily on mouse models. A paucity of human randomized
      controlled studies exists for cleft palate repair, and so far, tissue engineering
      approaches are limited. In this review, we discuss the development of the palate,
      explain the basic science behind normal and pathologic palate development in
      humans as well as mouse models and elaborate on how these studies may lead to
      future advances in palatal tissue engineering and cleft palate treatments.

PMID- 21964249
TI  - Neural circuits underlying the generation of theta oscillations.
AB  - Theta oscillations represent the neural network configuration underlying active
      awake behavior and paradoxical sleep. This major EEG pattern has been extensively
      studied, from physiological to anatomical levels, for more than half a century.
      Nevertheless the cellular and network mechanisms accountable for the theta
      generation are still not fully understood. This review synthesizes the current
      knowledge on the circuitry involved in the generation of theta oscillations, from
      the hippocampus to extra hippocampal structures such as septal complex,
      entorhinal cortex and pedunculopontine tegmentum, a main trigger of theta state
      through direct and indirect projections to the septal complex. We conclude with a
      short overview of the perspectives offered by technical advances for deciphering
      more precisely the different neural components underlying the emergence of theta
      oscillations.

PMID- 21964250
TI  - In vitro drug treatments reduce the deleterious effects of aggregates containing
      polyAla expanded PHOX2B proteins.
AB  - Heterozygous in frame duplications of the PHOX2B gene, leading to polyalanine
      (polyAla) expansions ranging from +5 to +13 residues of a 20-alanine stretch,
      have been identified in the vast majority of patients affected with Congenital
      Central Hypoventilation Syndrome (CCHS), a rare neurocristopathy characterized by
      absence of adequate autonomic control of respiration with decreased sensitivity
      to hypoxia and hypercapnia. Ventilatory supports such as tracheostomy, nasal mask
      or diaphragm pacing represent the only options available for affected. We have
      already shown that the severity of the CCHS phenotype correlates with the length
      of polyAla expansions, ultimately leading to formation of toxic intracytoplasmic
      aggregates and impaired PHOX2B mediated transactivation of target gene promoters,
      such as DBH. At present, there is no specific treatment to reduce cell aggregates
      and to ameliorate patients' respiration. In this work, we have undertaken in
      vitro analyses aimed at assessing the effects of molecules on the cellular
      response to polyAla PHOX2B aggregates. In particular, we tested 17-AAG,
      ibuprofen, 4-PBA, curcumin, trehalose, congo red and chrysamine G for their
      ability to i) recover the nuclear localisation of polyAla expanded PHOX2B, ii)
      rescue of PHOX2B mediated transactivation of the DBH promoter, and iii) clearance
      of PHOX2B (+13 Ala) aggregates. Our data have suggested that 17-AAG and curcumin
      are effective in vitro in both rescuing the nuclear localization and
      transactivation activity of PHOX2B carrying the largest expansion of polyAla and
      promoting the clearance of aggregates of these mutant proteins inducing molecular
      mechanisms such as ubiquitin-proteasome (UPS), autophagy and heat shock protein
      (HSP) systems.

PMID- 21964251
TI  - Early life stress triggers sustained changes in histone deacetylase expression
      and histone H4 modifications that alter responsiveness to adolescent
      antidepressant treatment.
AB  - Early life stress can elicit long-lasting changes in gene expression and
      behavior. Recent studies on rodents suggest that these lasting effects depend on
      the genetic background. Whether epigenetic factors also play a role remains to be
      investigated. Here we exposed the stress-susceptible mouse strain Balb/c and the
      more resilient strain C57Bl/6 to a powerful early life stress paradigm, infant
      maternal separation. In Balb/c mice, infant maternal separation led to decreased
      expression of mRNA encoding the histone deacetylases (HDACs) 1, 3, 7, 8, and 10
      in the forebrain neocortex in adulthood, an effect accompanied by increased
      expression of acetylated histone H4 proteins, especially acetylated H4K12
      protein. These changes in HDAC expression and histone modifications were not
      detected in C57Bl/6 mice exposed to early life stress. Moreover, a reversal of
      the H4K12 hyperacetylation detected in infant maternally separated Balb/c mice
      (achieved with chronic adolescent treatment with a low dose of theophylline that
      only activates HDACs) worsened the abnormal emotional phenotype resulting from
      this early life stress exposure. In contrast, fluoxetine, a drug with potent
      antidepressant efficacy in infant maternally separated Balb/c mice, potentiated
      all histone modifications triggered by early life stress. Moreover, in non
      stressed Balb/c mice, co-administration of an HDAC inhibitor and fluoxetine, but
      not fluoxetine alone, elicited antidepressant effects and also triggered changes
      in histone H4 expression that were similar to those provoked by fluoxetine
      treatment of mice exposed to early life stress. These results suggest that Balb/c
      mice develop epigenetic modifications after early life stress exposure that, in
      terms of the emotive phenotype, are of adaptive nature, and that enhance the
      efficacy of antidepressant drugs.

PMID- 21964252
TI  - Progressive myopathy in an inducible mouse model of oculopharyngeal muscular
      dystrophy.
AB  - The genetic basis of oculopharyngeal muscular dystrophy (OPMD) is a short
      expansion of a polyalanine tract (normal allele: 10 alanines, mutant allele: 11
      17 alanines) in the nuclear polyadenylate binding protein PABPN1 which is
      essential for controlling poly(A) tail length in messenger RNA. Mutant PABPN1
      forms nuclear inclusions in OPMD muscle. To investigate the pathogenic role of
      mutant PABPN1 in vivo, we generated a ligand-inducible transgenic mouse model by
      using the mifepristone-inducible gene expression system. Induction of ubiquitous
      expression of mutant PABPN1 resulted in skeletal and cardiac myopathy.
      Histological changes of degenerative myopathy were preceded by nuclear inclusions
      of insoluble PABPN1. Downregulation of mutant PABPN1 expression attenuated the
      myopathy and reduced the nuclear burden of insoluble PABPN1. These results
      support association between mutant PABPN1 accumulation and degenerative myopathy
      in mice. Resolution of myopathy in mice suggests that the disease process in OPMD
      patients may be treatable.

PMID- 21964254
TI  - Calcitonin gene-related peptide expression levels predict motor neuron
      vulnerability in the superoxide dismutase 1-G93A mouse model of amyotrophic
      lateral sclerosis.
AB  - In amyotrophic lateral sclerosis (ALS) some motor neurons degenerate while others
      survive. The molecular mechanisms underlying this selective vulnerability and
      resistance, respectively, are poorly understood. Since the neuropeptide,
      calcitonin gene-related peptide (CGRP), is expressed by many but not all motor
      neurons, we asked if motor neuron CGRP levels predict their vulnerability in the
      SOD1-G93A mouse model of ALS. In wild type mice three types of somatic motor
      neurons were distinguished based on their CGRP expression pattern, i.e. highCGRP,
      lowCGRP, and nonCGRP. Since motor nuclei III, IV and VI contained mostly nonCGRP
      motor neurons, they defined the oculomotor group. In comparison, the facial group
      (nuclei V, VII and XII) contained equal numbers of all three types, while the
      spinomedullary group (ambiguus nucleus and lumbar spinal cord) contained mainly
      highCGRP motor neurons. Analysis on the transcript level, and of mice lacking the
      alphaCGRP isoform, revealed that these group differences in CGRP expression were
      predominantly based on alphaCGRP. At disease end-stage in SOD1-G93A mice, group
      specific extent of motor neuron loss correlated with CGRP expression as neurons
      with highCGRP were reduced by 80%, those with lowCGRP by 50%, and nonCGRP motor
      neurons were not significantly affected in all three groups. Finally, highCGRP
      motor neuron degeneration preceded lowCGRP motor neuron degeneration during
      disease progression. Our analysis revealed that the relative abundance of CGRP
      mRNA and immunoreactivity in motor neurons predicts their vulnerability. CGRP may
      be an autocrine or paracrine factor promoting motor neuron degeneration in this
      ALS model.

PMID- 21964253
TI  - Adenosine A2a receptor antagonists attenuate striatal adaptations following
      dopamine depletion.
AB  - The motor symptoms of Parkinson's disease (PD) are widely thought to arise from
      an imbalance in the activity of the two major striatal efferent pathways
      following the loss of dopamine (DA) signaling. In striatopallidal, indirect
      pathway spiny projection neurons (iSPNs), intrinsic excitability rises following
      the loss of inhibitory D2 receptor signaling. Because these receptors are
      normally counterbalanced by adenosine A2a adenosine receptors, antagonists of
      these receptors are being examined as an adjunct to conventional pharmacological
      therapies. However, little is known about the effects of sustained A2a receptor
      antagonism on striatal adaptations in PD models. To address this issue, the A2a
      receptor antagonist SCH58261 was systemically administered to DA-depleted mice.
      After 5 days of treatment, the effects of SCH58261 on iSPNs were examined in
      brain slices using electrophysiological and optical approaches. SCH58261
      treatment did not prevent spine loss in iSPNs following depletion, but did
      significantly attenuate alterations in synaptic currents, spine morphology and
      dendritic excitability. In part, these effects were attributable to the ability
      of SCH58261 to blunt the effects of DA depletion on cholinergic interneurons,
      another striatal cell type that co-expresses A2a and D(2) receptors.
      Collectively, these results suggest that A2a receptor antagonism improves
      striatal function in PD models by attenuating iSPN adaptations to DA depletion.

PMID- 21964256
TI  - Identification of novel signaling components in genistein-regulated signaling
      pathways by quantitative phosphoproteomics.
AB  - Isolated from soybeans, genistein is an isoflavonoid that exhibits anti
      carcinogenic effects. Genistein could induce G2/M arrest and apoptosis of various
      cancer cells in vivo and in vitro. Although ERK1/2, AKT, p90RSK and NFkappaB were
      previously found to be regulated by genistein, most of signaling components in
      genistein-inhibited signaling pathways were still unknown. Here, we used SILAC
      quantitative phosphoproteomics to globally identify the phosphoproteins and their
      regulatory sites in signaling pathways mediated by genistein. We detected 1177
      phosphorylation sites on 635 unique proteins; among them, 320 phosphorylation
      sites on 222 unique phosphopeptides representing 215 non-redundant proteins were
      modulated at least 1.5-folds by genistein. Apart from ERK1/2, PI3K, p90RSK, Bad
      and topoisomerase that are known genistein-regulated effectors, many novel
      phosphoproteins were identified for the first time to be involved in genistein
      regulated signal transduction networks. They mainly include 9 receptors, 5 signal
      adaptors, 13 protein kinases, 2 protein phosphatase regulatory subunits, and 14
      transcription regulators. Several of these phosphoproteins have been proven to be
      involved in G2/M arrest or apoptosis such as GPCRs, DCC, NCK1, TNK2, BTK,
      TP53BP1, BCLAF, MAX and MAG. This dataset provides valuable insights into the
      cancer-related phosphorylation signaling pathways regulated by genistein.

PMID- 21964255
TI  - Dopamine abnormalities in the neocortex of patients with temporal lobe epilepsy.
AB  - Experiments were designed to evaluate different variables of the dopaminergic
      system in the temporal cortex of surgically treated patients with temporal lobe
      epilepsy (TLE) associated with mesial sclerosis (MTLE, n=12) or with cerebral
      tumor or lesion (n=8). In addition, we sought to identify dopaminergic
      abnormalities in those patients with epilepsy that had comorbid anxiety and
      depression. Specifically, we investigated changes in dopamine and its
      metabolites, D1 and D2 receptors, tyrosine hydroxylase (TH) and dopamine
      transporter. Results obtained from patients with epilepsy were compared with
      those found in experiments using autopsy material. The neocortex of patients with
      MTLE demonstrated high D1 expression (1680%, p<0.05) and binding (layers I-II,
      31%, p<0.05; layers V-VI, 28%, p<0.05), and decreased D2 expression (77%,
      p<0.05). The neocortex of patients with TLE secondary to cerebral tumor or lesion
      showed high expression of D1 receptors (1100%, p<0.05), and D2-like induced
      activation of G proteins (layers I-II, 503%; layers III-IV, 557%; layers V-VI,
      964%, p<0.05). Both epileptic groups presented elevated binding to the dopamine
      transporter and low tissue content of dopamine and its metabolites. Analysis
      revealed the following correlations: a) D1 receptor binding correlated negatively
      with seizure onset age and seizure frequency, and positively with duration of
      epilepsy; b) D2 receptor binding correlated positively with age of seizure onset
      and negatively with duration of epilepsy; c) dopamine transporter binding
      correlated positively with duration of epilepsy and frequency of seizures; d) D2
      like induced activation of G proteins correlated positively with the age of
      patients. When compared with autopsies and patients with anxiety and depression,
      patients without neuropsychiatric disorders showed high D2-like induced
      activation of G proteins, an effect that correlated positively with age of
      patient and seizure onset age, and negatively with duration of epilepsy. The
      present study suggests that alterations of the dopaminergic system result from
      epileptic activity and could be involved in the physiopathology of TLE and the
      comorbid anxiety and depression.

PMID- 21964257
TI  - Quantitative proteomic analysis of cyclosporine-induced toxicity in a human
      kidney cell line and comparison with tacrolimus.
AB  - The calcineurin-inhibitors (CNIs) cyclosporine (CsA) and tacrolimus (TAC) remain
      the pillars of modern immunosuppression regimens used in solid organ
      transplantation. Nephrotoxicity is an adverse effect that limits their successful
      use. The precise molecular mechanisms underlying this nephrotoxicity remain
      unclear. Using SILAC together with LC-MALDI-TOF/TOF, we investigated the CNIs
      induced proteomic perturbations in renal cells. Among the 495 proteins
      quantifiable in both forward and reverse SILAC, 69 displayed CsA-induced
      perturbations: proteins involved in ER-stress/protein folding, apoptosis,
      metabolism/transport or cytoskeleton pathways were up-regulated, while
      cyclophilin B as well as nuclear and RNA-processing proteins were down-regulated.
      Co-administration of CsA with the antioxidant N-acetylcysteine significantly
      decreased lipid peroxidation and also partially corrected the CsA-induced
      unfolded protein response. TAC toxicity profile was apparently different from
      that of CsA, especially without perturbation of cyclophilins A and B, up
      regulation of ER-chaperones nor down-regulation of a number of nuclear proteins.
      These results provide a new insight and are consistent with recent data regarding
      the molecular mechanisms of CNIs-induced nephrotoxicity. Our findings offer new
      directions for future research aiming to identify specific biomarkers of CsA
      nephrotoxicity.

PMID- 21964258
TI  - iTRAQ-based quantitative proteomic analysis of Gloeothece sp. PCC 6909:
      Comparison with its sheathless mutant and adaptations to nitrate deficiency and
      sulfur limitation.
AB  - Gloeothece sp. PCC 6909 is a unicellular N(2)-fixing cyanobacterium with a well
      defined and highly developed sheath surrounding its cells. A sheathless mutant of
      this strain was previously obtained by chemical mutagenesis and, although lacking
      the sheath, it releases large amounts of polysaccharides into the culture medium.
      To provide a global understanding on the metabolic differences between the two
      phenotypes, the proteomes of the wild type and mutant were analyzed using a cross
      species proteomics approach coupled with iTRAQ isobaric tagging technology, since
      their genome sequences are not yet available. Effects arising from the
      presence/absence of nitrate and sulfur are presented as two metabolically
      directed follow-up iTRAQ studies. These nutrients are believed to play a major
      role in Gloeothece's metabolism, including the production of extracellular
      polymeric substances - EPS. 454, 124, and 53 proteins were identified and
      reliably quantified using homology anchoring approaches for iTRAQ previously
      described. The results obtained strongly suggest that the chemical mutagenesis
      affected the regulation of a number of key cellular processes, as revealed by the
      significant fold changes observed for proteins covering a large spectrum of
      functional groups. Moreover, they provide new insights on the adaptations of
      Gloeothece cells to nitrate-deficiency and sulfur-limitation.

PMID- 21964259
TI  - Palladium-catalyzed Heck-type reaction of oxime ether bearing a pendant vinyl
      iodide moiety.
AB  - A Pd(0)-catalyzed intramolecular Heck-type reaction of oxime ether has been
      developed, providing convenient access to heterocyclic oximes.

PMID- 21964260
TI  - An evolutionary advantage for extravagant honesty.
AB  - A game-theoretic model of handicap signalling over a pair of signalling channels
      is introduced in order to determine when one channel has an evolutionary
      advantage over the other. The stability conditions for honest handicap signalling
      are presented for a single channel and are shown to conform with the results of
      prior handicap signalling models. Evolutionary simulations are then used to show
      that, for a two-channel system in which honest signalling is possible on both
      channels, the channel featuring larger advertisements at equilibrium is favoured
      by evolution. This result helps to address a significant tension in the handicap
      principle literature. While the original theory was motivated by the prevalence
      of extravagant natural signalling, contemporary models have demonstrated that it
      is the cost associated with deception that stabilises honesty, and that the
      honest signals exhibited at equilibrium need not be extravagant at all. The
      current model suggests that while extravagant and wasteful signals are not
      required to ensure a signalling system's evolutionary stability, extravagant
      signalling systems may enjoy an advantage in terms of evolutionary attainability.

PMID- 21964261
TI  - Robust modeling of appetite regulation.
AB  - The interaction between appetite activation and the energy content of the brain
      and the body is mathematically modeled. General influence functions with
      saturation are used to describe the interaction. The resulting class of models is
      investigated with respect to the circadian periodicity of human food intake. We
      show that very weak and physiologically reasonable assumptions on the
      constitutive functions are sufficient to validate the indispensable role of the
      brain as energy consumer in appetite regulation. Subsequently, implications from
      our systemic investigations of metabolic systems can be drawn although the
      quantification of the underlying regulatory pathways is uncertain, incomplete, or
      incompletely understood.

PMID- 21964262
TI  - Production of recombinant proteins by yeast cells.
AB  - Yeasts are widely used in production of recombinant proteins of medical or
      industrial interest. For each individual product, the most suitable expression
      system has to be identified and optimized, both on the genetic and fermentative
      level, by taking into account the properties of the product, the organism and the
      expression cassette. There is a wide range of important yeast expression hosts
      including the species Saccharomyces cerevisiae, Pichia pastoris, Hansenula
      polymorpha, Kluyveromyces lactis, Schizosaccharomyces pombe, Yarrowia lipolytica
      and Arxula adeninivorans, with various characteristics such as being thermo
      tolerant or halo-tolerant, rapidly reaching high cell densities or utilizing
      unusual carbon sources. Several strains were also engineered to have further
      advantages, such as humanized glycosylation pathways or lack of proteases.
      Additionally, with a large variety of vectors, promoters and selection markers to
      choose from, combined with the accumulated knowledge on industrial-scale
      fermentation techniques and the current advances in the post-genomic technology,
      it is possible to design more cost-effective expression systems in order to meet
      the increasing demand for recombinant proteins and glycoproteins. In this review,
      the present status of the main and most promising yeast expression systems is
      discussed.

PMID- 21964264
TI  - How to use the bromides. June 1881.

PMID- 21964263
TI  - Overexpression of Far1, a cyclin-dependent kinase inhibitor, induces a large
      transcriptional reprogramming in which RNA synthesis senses Far1 in a Sfp1
      mediated way.
AB  - The FAR1 gene encodes an 830 residue bifunctional protein, whose major function
      is inhibition of cyclin-dependent kinase complexes involved in the G1/S
      transition. FAR1 transcription is maximal between mitosis and early G1 phase.
      Enhanced FAR1 transcription is necessary but not sufficient for the pheromone
      induced G1 arrest, since FAR1 overexpression itself does not trigger cell cycle
      arrest. Besides its well established role in the response to pheromone, recent
      evidences suggest that Far1 may also regulate the mitotic cell cycle progression:
      in particular, it has been proposed that Far1, together with the G1 cyclin Cln3,
      may be part of a cell sizer mechanism that controls the entry into S phase. Far1
      is an unstable protein throughout the cell cycle except during G1 phase. Far1
      levels peak in newborn cells as a consequence of a burst of synthetic activity at
      the end of the previous cycle, and the amounts per cell remain roughly constant
      during the G1 phase. Phosphorylation (at serine 87) by Cdk1-Cln complexes primes
      Far1 for ubiquitin-mediated proteolysis. By coupling a genome-wide
      transcriptional analysis of FAR1-overexpressing and far1Delta cells grown in
      ethanol- or glucose-supplemented minimal media with a range of phenotypic
      analysis, we show that FAR1 overexpression not only coordinately increases RNA
      and protein accumulation, but induces strong transcriptional remodeling,
      metabolism being the most affected cellular property, suggesting that the
      Far1/Cln3 sizer regulates cell growth either directly or indirectly by affecting
      metabolism and pathways known to modulate ribosome biogenesis. A crucial role in
      mediating the effect of Far1 overexpression is played by the Sfp1 protein, a key
      transcriptional regulator of ribosome biogenesis, whose presence is mandatory to
      allow a coordinated increase in both RNA and protein levels in ethanol-grown
      cells.

PMID- 21964265
TI  - Bromization: the truths we know about the psychopharmacology of schizophrenia.

PMID- 21964266
TI  - Stalking by patients: doctors' experiences in a Canadian urban area.
AB  - OBJECTIVE: Stalking involves recurrent unwanted communication, harassment, and
      intrusive behaviors. The aim of this study was to examine doctors' experiences of
      being stalked by their patients in a Canadian urban area. A questionnaire
      designed to study the nature and prevalence of stalking experiences among
      physicians was sent to 3159 randomly chosen physicians in the Greater Toronto
      Area. Of the 1190 physicians who responded, 14.9% reported having been stalked.
      Although both male and female patients were stalkers, their motives and stalking
      behaviors were dissimilar. Psychiatrists, surgeons, and OB/GYNs reported the
      highest rates of being stalked. Both male and female physicians are at an
      increased risk of being stalked by patients who may feel loving feelings or anger
      and resentment. Varying reasons behind the stalking may account for the differing
      rates between specialties. Physicians may benefit from recognition of behaviors
      that tended to precede the onset of stalking behavior.

PMID- 21964267
TI  - Mental disorders among frequent attenders in primary care: a comparison with
      routine attenders.
AB  - Frequent attenders account for a large proportion of primary care (PC) contacts,
      referrals, and prescriptions. Psychosocial and emotional distress is related to
      the high use of health services. Few studies have focused on the association
      between mental disorders assessed using structured interviews and frequent use of
      PC services.The aim of this study was to determine the factors associated with
      frequent attendance at primary healthcare units, focusing specifically on mental
      disorders. A two-phase screening epidemiological study comparing frequent
      attenders and routine attenders in five primary health care units was designed.
      Three hundred eighteen frequent attenders and 203 patients who attended the same
      units on a routine basis were compared. Sociodemographic and clinical data were
      obtained from statistical records and medical charts. Patients with a total score
      equal or higher than 7 points on the General Health Questionnaire-28 (GHQ-28)
      were interviewed using the Schedules for Clinical Assessment in Neuropsychiatry.
      All the scores obtained on the GHQ were statistically different in the two
      populations. Frequency of mental disorders also differed significantly between
      both groups, with somatoform and affective disorders being the most prevalent ICD
      10 categories among frequent attenders. The presence of depressive disorders and
      somatoform disorders is the most powerful predictive factor for frequent
      attendance. High comorbidity was found among frequent attenders with somatoform
      disorder. Frequent attendance at primary healthcare units is associated with
      depressive and somatoform disorders. Psychiatric comorbidity could be a
      confounder, particularly because affective and somatoform disorders often overlap
      in PC patients.

PMID- 21964268
TI  - Personality subtypes of adolescents who attempt suicide.
AB  - Research suggests that personality pathology is shared among a considerable
      portion of adolescents presenting suicidal behavior. Furthermore, heterogeneity
      of personality within this population suggests a need to tease apart different
      types of attempters. The goal of this study was to identify the personality
      subtypes of adolescents who attempt suicide. We analyzed data on 266 adolescents,
      ages 13 to 18 years, with a history of at least one suicide attempt who were
      selected by treating clinicians for having at least some degree of personality
      problems. We used a Q-factor analysis to identify subtypes based on the Shedler
      Westen Assessment Procedure-II for Adolescents (a 200-item measure of personality
      pathology used by clinically experienced observers). We derived six subtypes:
      Externalizing, Internalizing, Emotionally dysregulated, High functioning,
      Narcissistic, and Immature. The subtypes differed on measures of adaptive
      functioning, axis I and II pathology, and etiology. Adolescents who attempt
      suicide constitute a heterogeneous group, and they vary meaningfully on a measure
      of personality pathology. Interventions targeting suicidal behaviors in
      adolescents should consider individual differences.

PMID- 21964269
TI  - Do humor styles mediate or moderate the relationship between self-criticism and
      neediness and depressive symptoms?
AB  - This study examined whether, in a community sample of Israeli adults (N = 335),
      benign (i.e., affiliative and self-enhancing) and injurious (i.e., aggressive and
      self-defeating) humor styles mediated or moderated the relationship between self
      criticism and neediness, two traits that confer vulnerability to depression, on
      the one hand, and levels of depressive symptoms, on the other. There was no
      evidence of any moderating effect of humor styles on the relationship between
      self-criticism and neediness and depressive symptoms. However, results indicated
      that the use of injurious styles of humor mediated the relationship between self
      criticism and depressive symptoms as well as the relationship between neediness
      and depressive symptoms. Moreover, the relationship between neediness and
      depressive symptoms was also mediated by low levels of benign humor. These
      findings may have important implications for theories concerning vulnerability to
      depressive symptoms and intervention strategies.

PMID- 21964270
TI  - Selective attention to threat bias in delusion-prone individuals.
AB  - The study examined the selective attention to threat bias in delusion-prone
      individuals recruited from New Religious Movements (NRMs). Twenty-seven delusion
      prone NRM individuals were compared with 25 individuals with psychotic disorders
      and 63 non-delusion-prone individuals on a Stroop task, together with psychotic
      and delusion proneness measures. NRM individuals showed significantly lower
      levels of selective attention to threat bias compared with individuals with
      psychotic disorders but not with non-delusion-prone individuals. Selective
      attention to threat bias was also not correlated with distress associated with
      delusional ideation. These findings may be specific to delusion-prone NRM
      individuals. The absence of the selective attention to threat bias may be related
      to levels of safety and security among members of NRMs.

PMID- 21964271
TI  - Alexithymia and its relationship to dissociation in patients with panic disorder.
AB  - Conditions that impede the regulation of emotional arousal, such as alexithymia
      and dissociation, may underlie panic attacks. This study aimed to evaluate the
      relationship between alexithymia and dissociation in patients with panic disorder
      (PD). We assessed 95 PD outpatients with regard to alexithymia (20-item Toronto
      Alexithymia Scale), dissociation (Dissociation Experience Scale), and overall
      psychological distress (Symptom Checklist 90-Revised, Global Severity Index).
      Regression analyses revealed a positive correlation between alexithymia and
      dissociation, even when the Global Severity Index was controlled for. A specific
      link was observed between "difficulty in identifying feelings" and
      "depersonalization/derealization." Patients who showed the pathological form of
      dissociation had higher levels of alexithymia, with particular regard to
      "difficulty in identifying feelings" and, to a smaller extent, "difficulty in
      describing feelings." These results support a strong relationship between
      alexithymia and dissociation in patients with PD. Assessing alexithymia and
      dissociation at the outset of therapy may be helpful for individualized therapy
      planning.

PMID- 21964272
TI  - Stigma apprehension among adolescents discharged from brief psychiatric
      hospitalization.
AB  - This study explores stigma apprehension (fear of being devalued or rejected) and
      its correlates among 102 adolescents, interviewed within 7 days of discharge from
      their first psychiatric hospitalization. Components of the Model of Stigma
      Induced Identity Threat by Major and O'Brien (Annu Rev Psychol 56:393-421, 2005)
      comprise the study model, including collective stigma representations and group
      and domain identification; additional clinical, personal, and contextual
      characteristics such as social affiliation, interpersonal support, self
      identification as having a mental disorder, and perceived need for others'
      approval were added to the model. We found that, on average, the participants
      reported "a little" stigma apprehension, and 21% reported substantial stigma
      apprehension. Multivariate analysis demonstrated that higher stigma apprehension
      was most associated with the female sex, younger age at initiation of mental
      health treatment, lower self-esteem, greater need for others' approval, more
      experiences with personal stigmatization, and not identifying or affiliating with
      peers who have mental health or behavior challenges. These factors collectively
      accounted for 46% of the variance. The study's findings particularly highlight
      the role of social context and external contingencies of self-worth in
      determining adolescents' perceptions of stigma-related threat.

PMID- 21964273
TI  - Psychometric properties of an instrument for measuring threat/control-override
      symptoms.
AB  - Threat/control-override symptoms refer to delusional persecutory thoughts and
      feelings of losing control over mind and body. The Threat/Control-Override
      Questionnaire (TCOQ) was developed to assess such symptoms, and the purpose of
      the present study was to examine the psychometric properties of this measure in
      nonclinical students (n = 759) and acute and stabilized psychotic patients (n =
      111 and 33, respectively). Factor analysis of TCOQ data in students and acute
      psychotic patients yielded a two-factor solution, with components referring to
      "threat" and "control-override" symptoms. Internal consistency and test-retest
      reliability were satisfactory and concurrent and discriminant validity were shown
      by a meaningful pattern of correlations with other self-report and interview
      measures. Group comparisons showed that patients displayed significantly higher
      scores on the TCOQ than did the nonclinical students. Altogether, it can be
      concluded that the TCOQ is a reliable and valid index for assessing feelings of
      persecution and losing control.

PMID- 21964274
TI  - Interrater reliability of the assessment of DSM-IV Axis IV psychosocial stressors
      and environmental problems.
AB  - The interrater reliability of the DSM-IV axis IV psychosocial stressors was
      investigated in a retrospective chart review study. The complete charts of 98
      patients admitted to a specialized psychiatric ward were independently evaluated
      by three trained clinicians and rated on a questionnaire form comprising the
      presence and severity of the nine psychosocial stressors of DSM-IV axis IV
      (DSMSTR9; absent scored 0; mild, 1-3; moderate, 4-6; severe, 6-10). Chance
      corrected intraclass correlations (ICC) were calculated for the interrater
      reliability of DSMSTR9 stressors. DSMSTR9 stressors exhibited sufficiently high
      levels of interrater reliability regarding presence (ICC = 0.560-0.943; p <
      0.0005) and severity (ICC = 0.584-0.953; p < 0.0005) of stressors with slightly
      higher ICCs for severity assessments. Problems related to the social environment
      showed the lowest ICCs. According to the present results, the presence and
      severity of DSM-IV axis IV stressors can be scored sufficiently reliably even in
      retrospective studies. Including the assessment of presence and severity of DSM
      IV axis IV psychosocial and environmental problems in future DSM versions, using
      a 4-point scale can therefore be recommended.

PMID- 21964275
TI  - Factors associated with interest in receiving help for mental health problems in
      combat veterans returning from deployment to Iraq.
AB  - Mental health problems in service members often go untreated. This study focused
      on factors related to interest in receiving help in a survey sample of 577 combat
      veterans who were screened positive for posttraumatic stress disorder,
      depression, or generalized anxiety disorder 3 months after returning from Iraq.
      Over three quarters of respondents recognized that they had a current problem,
      but only 40% were interested in receiving help. Interest in receiving help was
      associated with recognizing a problem and receiving mental health services in the
      past year. More negative attitudes toward mental health care were associated with
      lower interest in receiving help; paradoxically, more negative perceptions of
      unit stigma were associated with increased interest in receiving help. Further
      studies are needed to better define the relationship between stigma perceptions,
      interest in receiving care, and actual care utilization and to determine whether
      attitudes toward mental health care can be modified through changes in how care
      is delivered. Attitudes toward mental health care should be considered in
      treatment interventions.

PMID- 21964276
TI  - Subjective disturbance of perception is related to facial affect recognition in
      schizophrenia.
AB  - To examine the relationship between facial affect recognition (FAR) and
      subjective perceptual disturbances (SPDs), we assessed SPDs in 82 patients with
      DSM-IV schizophrenia (44 with first-episode psychosis [FEP] and 38 with multiple
      episodes [ME]) using two subscales of the Frankfurt Complaint Questionnaire
      (FCQ), WAS (simple perception) and WAK (complex perception). Emotional judgment
      ability was assessed using Ekman and Friesen's FAR task. Impaired recognition of
      emotion correlated with scores on the WAS but not on the WAK. The association was
      significant in the entire group and in the ME group. FAR was more impaired in the
      ME than in the FEP group. Our findings suggest that there is a relationship
      between SPDs and FAR impairment in schizophrenia, particularly in multiple
      episode patients.

PMID- 21964277
TI  - Changes in depressive symptoms and social functioning in the sequenced treatment
      alternatives to relieve depression study.
AB  - Major depressive disorder (MDD) profoundly affects social functioning, including
      the ability to enjoy social activities with peers, friends, and family members.
      We sought to compare changes in social functioning and depressive symptoms in the
      first level of the Sequenced Treatment Alternatives to Relieve Depression
      (STAR*D) study. Adult outpatients (N = 2876) with diagnoses of MDD were treated
      using flexible doses of citalopram for up to 14 weeks. We compared the change
      over the course of treatment in the social activities item of the Work and Social
      Adjustment Scale to the change in individual items of the Quick Inventory of
      Depressive Symptoms-Self-Rated (QIDS-SR). Improvement in social functioning was
      modestly positively correlated with improvement in sad mood,
      concentration/decision making, involvement, and energy/fatigability. Only 16% to
      22% of the variance in the change in social functioning was accounted for by
      these symptoms, and only 32% was accounted for by the total QIDS-SR score. In
      this large real-world sample of outpatients treated using citalopram, changes in
      depressive symptoms do not entirely explain improvements in social functioning.

PMID- 21964278
TI  - Treatment response for late-life generalized anxiety disorder: moving beyond
      symptom-based measures.
AB  - Response to treatment of late-life generalized anxiety disorder has been defined
      by a variety of methods, all based on statistically significant reductions in
      symptom severity. However, it is unknown whether these improvements in symptom
      severity are associated with meaningful differences in everyday functioning. The
      current study used four methods to define response to treatment for 115 primary
      care patients 60 years and older, with a principal or coprincipal diagnosis of
      generalized anxiety disorder. The methods examined included percentage of
      improvement, reliable change index, and minimal clinically significant
      differences. Agreement among classification methods and their associations with
      general and mental health-related quality of life were assessed. Results
      indicated moderate agreement among symptom-based classification methods and
      significant associations with measures of quality of life.

PMID- 21964279
TI  - Adherence disparities in mental health: opportunities and challenges.

PMID- 21964280
TI  - Complex modulation of peptidolytic activity of cathepsin D by sphingolipids.
AB  - Cathepsin D is an aspartic peptidase involved in cellular processes including
      proliferation and apoptosis and implicated in human pathologies such as cancer
      and neurodegeneration. Our knowledge about the relationship between proteolysis
      and bioactive sphingolipids is still very limited. Here, we describe a complex
      pattern of modulation of the peptidolytic activity of cathepsin D by
      sphingolipids. A panel of sphingolipid derivatives was screened in a FRET-based
      assay; these molecules demonstrated negative or positive modulation of cathepsin
      D peptidolytic activity, depending on the sphingolipid structure. Certain
      sphingosines and ceramides inhibited cathepsin D in the submicromolar range, and
      structural requirements for this inhibitory effect were evaluated. The
      interaction of cathepsin D with sphingolipids was also demonstrated by
      fluorescence polarization measurements and determined to follow a competitive
      inhibition mode. In contrast, monoester phosphosphingolipids, especially ceramide
      1-phosphate, were identified as activators of cathepsin D peptidolytic activity
      at submicromolar concentrations. Thus, sphingolipids and phosphosphingolipids,
      known to be antagonistic in their cell-signaling functions, displayed opposite
      modulation of cathepsin D. Sphingolipid-based modulators of cathepsin D are
      potentially involved in the control of cathepsin D-dependent processes and might
      serve as a scaffold for the development of novel regulators of this therapeutic
      target.

PMID- 21964281
TI  - Methods for analyzing phosphoinositides using mass spectrometry.
AB  - The polyphosphoinositides are key signaling lipids whose levels are tightly
      regulated within cells. As with other cellular lipids multiple species exist with
      distinct acyl chain makeups. There are methods which analyze the
      phosphoinositides as their deacylated derivatives which cannot address these
      distinct forms. Lipidomic analysis of the polyphosphoinositides has been hampered
      by difficulties with extraction and problems associated with binding of the
      lipids to surfaces. This review outlines the available MS methodologies,
      highlighting the difficulties associated with each. However, at present, no
      single methodology is available that can successfully and reproducibly quantitate
      each inositol phospholipid.

PMID- 21964283
TI  - Proteomics for identifying mechanisms and biomarkers of drug resistance in
      cancer.
AB  - A major problem in chemotherapy of cancer patients is drug resistance as well as
      unpredictable response to treatment. During chemotherapy, multiple alterations of
      genetics and epigenetics that contribute to chemoresistance take place,
      eventually impacting on disease outcome. A more complex picture of the mechanisms
      of drug resistance is now emerging through application of high-throughput
      proteomics technology. We have entered an exciting time where proteomics are
      being applied to characterize the mechanisms of drug resistance, and to identify
      biomarkers for predicting response to chemotherapy, thereby leading to
      personalized therapeutic strategies of cancer patients. Comparative proteomics
      have identified a large number of differentially expressed proteins associated
      with chemoresistance. Although roles and mechanisms of such proteins in
      chemoresistance need to be further proved, at least some of them may be potential
      biomarkers for predicting chemotherapeutic response. Herein, we review the recent
      advancements on proteomic investigation of chemoresistance in human cancer, and
      emphasize putative biomarkers for predicting chemotherapeutic response and
      possible mechanisms of chemoresistance identified through proteomic approaches.
      Suggested avenues for future work are discussed.

PMID- 21964284
TI  - Competition between an avoidance response and a safety signal: evidence for a
      single learning system.
AB  - Two experiments examined competition between an instrumental avoidance response
      and a Pavlovian safety signal for association with omission of electric shock in
      a human fear conditioning paradigm. Self-reported shock expectancies and skin
      conductance responses were consistent with blocking of learning of the
      instrumental contingency by prior training of the Pavlovian contingency, and vice
      versa. The results support the idea that a common learning mechanism underlies
      both Pavlovian and instrumental conditioning. The expectancy data suggest that
      this learning mechanism is cognitive in nature, and that Pavlovian and
      instrumental learning involve external and internal attributions, respectively.
      The procedure may thus serve as a laboratory model for attributional processes
      involved in the acquisition of threat expectancies in anxiety and anxiety
      disorders.

PMID- 21964282
TI  - Improvement of CXCR4 tracer specificity for PET imaging.
AB  - Tumors expressing the chemokine receptor CXCR4 have been reported to be more
      aggressive and to produce more metastatic seeding in specific organs, such as the
      bone marrow. However, evaluation of tumors for CXCR4 expression requires testing
      of ex vivo biopsy samples, and is not routinely done in cancer management. In
      prior work to address this issue, we and others have developed tracers for
      positron emission tomography (PET) that targeted CXCR4, but in addition to
      binding to CXCR4 these tracers also bound to red blood cells (and to other
      unrelated targets) in vivo. Here we report two new tracers based on the CXCR4
      peptide antagonist 4F-benzoyl-TN14003 (T140) that bind to CXCR4, but not to
      undesired targets. These tracers, NOTA-NFB and DOTA-NFB, show slight reductions
      in both 1) binding affinities for CXCR4 and 2) inhibition of CXCL12 induced
      migration, compared to T140, in vitro. Both NOTA-NFB and DOTA-NFB specifically
      accumulate in CXCR4-positive, but not CXCR4-negative, tumor xenografts in mice
      and allow clear visualization of CXCR4 expression by PET. Evaluation of NOTA-NFB
      and DOTA-NFB for their potential to mobilize immune cells and progenitor cells
      from the bone marrow to the peripheral blood revealed slightly reduced, but still
      comparable, results to the parent molecule T140. The tracers reported here may
      allow the evaluation of CXCR4 expression in primary tumors and metastatic
      nodules, and enable better informed, more personalized treatment for patients
      with cancer.

PMID- 21964285
TI  - Quality of life impairments among adults with social phobia: the impact of
      subtype.
AB  - Social phobia is characterized by extreme fear in social or performance
      situations in which the individual may be exposed to embarrassment or scrutiny by
      others, which creates occupational, social and academic impairment. To date,
      there are few data examining the relationship of social phobia impairments to
      quality of life. In this investigation, we examined how demographic
      characteristics, comorbidity, and social competence are related to quality of
      life among patients with social phobia and normal controls. In addition, we
      examined the impact of social phobia subtype. Results indicated that individuals
      with generalized social phobia had significantly impaired quality of life when
      compared to individuals with no disorder or individuals with nongeneralized
      social phobia. Comorbid disorders decreased quality of life only for patients
      with nongeneralized social phobia. Hierarchical linear regression revealed that a
      diagnosis of social phobia and observer ratings of social effectiveness exerted
      strong and independent effects on quality of life scores. Results are discussed
      in terms of the role of social anxiety, social competence, and comorbidity on the
      quality of life for adults with social phobia.

PMID- 21964286
TI  - Translational level of acetylcholine receptor alpha mRNA in mouse skeletal muscle
      is regulated by YB-1 in response to neural activity.
AB  - Y-box-binding protein 1 (YB-1) binds to mRNAs and affects translation. In this
      study, we focused on skeletal muscle, in which YB-1 expression is restricted to
      the early postnatal period, and found that YB-1 binds to acetylcholine receptor
      alpha-subunit (AChR alpha) mRNA. Although transcription of the AChR alpha gene is
      known to be regulated by myogenic transcription factors, translational control of
      the mRNA in response to neuromuscular transmission has not been examined. In
      undifferentiated C2C12 myoblasts, expression of AChR alpha remained at a low
      level. However, translation of the mRNA was increased by knockdown of YB-1.
      Continued overexpression of YB-1 prevented the cells from differentiating. In
      myotubes, which show clustering of AChRs, translation of the mRNA was induced
      within 3h after treatment with nicotine. The effect of nicotine was inhibited by
      alpha-bungarotoxin, and in the presence of cycloheximide the level of AChR alpha
      was reduced, even after nicotine treatment. Sucrose gradient analysis revealed
      that in nicotine-treated myotubes, YB-1-containing polysomes were shifted to the
      heavier-sedimenting fractions, and showed an apparent decrease in the amount of
      YB-1 bound to AChR alpha mRNA. These results suggest that in skeletal muscle
      cells, neural activity reduces the molar ratio of YB-1 relative to its binding
      AChR alpha mRNA, leading to an increase of ribosome binding to the mRNA, and thus
      activating translation. Furthermore, in postnatal growing mice, as has already
      been shown, the level of AChR alpha mRNA declined during the early period with
      maturation of neuromuscular synapses, but the translation level was found to
      increase transiently at postnatal day 10, when the level of YB-1 was markedly
      reduced. It is suggested that although the level of AChR alpha mRNA is reduced,
      the translation can be induced by alteration of the ratio of YB-1 protein to the
      mRNA.

PMID- 21964287
TI  - Phosphorylation/inactivation of PTEN by Akt-independent PI3K signaling in retinal
      pigment epithelium.
AB  - Retinal pigment epithelium (RPE) plays a critical role in vertebrate vision by
      providing functional and structural support to the retina. Degeneration of RPE by
      cumulative oxidative stresses or acute injury frequently results in retinal
      degenerative diseases, notably age-related macular degeneration (AMD). Moreover,
      it has been shown that phosphorylation-mediated inactivation of PTEN (phosphatase
      and tensin homolog) in RPE is closely linked to AMD-like retinal degeneration in
      mice [1]. In this study, we used AMD mouse models, in which chemokine (C-C motif)
      ligand 2 (Ccl2) or chemokine (C-C motif) receptor 2 (Ccr2) were genetically
      ablated, to examine mechanisms linking reactive oxygen species (ROS) to
      phosphorylation/inactivation of PTEN in RPE. We found that ROS levels were
      increased in these RPE cells in association with phosphorylation/inactivation of
      PTEN. Both PTEN phosphorylation/inactivation and consequent Akt activation in the
      RPE of AMD model mice were inhibited by antioxidant treatment, indicating a
      functional role for elevated intracellular ROS. We further discovered that PTEN
      phosphorylation in oxidatively stressed RPE was repressed by a phosphoinositide 3
      kinase (PI3K) inhibitor, but not by an Akt inhibitor. Taken together, these
      results suggest that ROS-activated PI3K potentiates AMD-related RPE pathogenesis
      through phosphorylation/inactivation of PTEN.

PMID- 21964288
TI  - Site-specific solvent exposure analysis of a membrane protein using unnatural
      amino acids and 19F nuclear magnetic resonance.
AB  - Membrane proteins play an essential role in cellular metabolism, transportation
      and signal transduction across cell membranes. The scarcity of membrane protein
      structures has thus far prevented a full understanding of their molecular
      mechanisms. Preliminary topology studies and residue solvent exposure analysis
      have the potential to provide valuable information on membrane proteins of
      unknown structure. Here, a (19)F-containing unnatural amino acid (trimethylfluoro
      phenylalanine, tfmF) was applied to accomplish site-specific (19)F spin
      incorporation at different sites in diacylglycerol kinase (DAGK, an Escherichia
      coli membrane protein) for site-specific solvent exposure analysis. Due to
      isotope effect on (19)F spins, a standard curve for (19)F-tfmF chemical shifts
      was drawn for varying solvent H(2)O/D(2)O ratios. Further site-specific (19)F
      solvent isotope shift analysis was conducted for DAGK to distinguish residues in
      water-soluble loops, interfacial areas or hydrophobic membrane regions. This site
      specific solvent exposure analysis method could be applied for further
      topological analysis of other membrane proteins.

PMID- 21964289
TI  - Diverse beta subunits of heterotrimeric G proteins are present in thyroid plasma
      membranes.
AB  - The functioning of heterotrimeric G protein alpha subunits in the transduction of
      hormonal signals to appropriate intracellular responses is well recognized. Much
      less is known about the distribution of isoforms and functions of G protein beta
      subunits. Here, using specific antibodies, we documented that in plasma membranes
      of the thyroid cell line Nthy-ori 3-1 all Gbeta isoforms-Gbeta(1), Gbeta(2),
      Gbeta(3), Gbeta(4) and Gbeta(5) are present, while the Gbeta(3) occurs in minute
      amount. In plasma membrane fraction isolated from pooled postoperative thyroids
      of patients with nodular goiter and Graves' disease, the Gbeta(1), Gbeta(2),
      Gbeta(4) and Gbeta(5) subunits were found, whereas Gbeta(3) could not be
      detected. Competition studies revealed that the Gbeta(2) is the principal Gbeta
      subunit in membranes from cultured thyroid cells, originated from normal thyroid,
      as well as in membranes from patients' thyroids. This suggests that Gbeta(2)
      subunit cooperates with Galpha(s) subunit, the most active of the Galpha
      variants, during stimulation of adenylate cyclase which constitutes the main
      route of physiological thyroid stimulation.

PMID- 21964290
TI  - Cell death pathology: perspective for human diseases.
AB  - Apoptosis, a genetically regulated form of cell death with distinct biochemical
      and morphological features, plays a relevant physiological and pathological role
      in the organism, being pivotal in the maintenance of tissue development and
      homeostasis in the adult as well as in the regulation of immune responses.
      Deregulation of this process causes several human disorders including cancer,
      autoimmune and neurodegenerative diseases. Thus, modulation of the apoptotic
      process and of cell death in general, is a potential therapeutic approach for the
      treatment of several human pathologies.

PMID- 21964291
TI  - Stimulation of the amino acid transporter SLC6A19 by JAK2.
AB  - JAK2 (Janus kinase-2) is expressed in a wide variety of cells including tumor
      cells and contributes to the proliferation and survival of those cells. The gain
      of function mutation (V617F)JAK2 mutant is found in the majority of
      myeloproliferative diseases. Cell proliferation depends on the availability of
      amino acids. Concentrative cellular amino acid uptake is in part accomplished by
      Na(+) coupled amino acid transport through SLC6A19 (B(0)AT). The present study
      thus explored whether JAK2 activates SLC6A19. To this end, SLC6A19 was expressed
      in Xenopus oocytes with or without wild type JAK2, (V617F)JAK2 or inactive
      (K882E)JAK2 and electrogenic amino acid transport determined by dual electrode
      voltage clamp. In SLC6A19-expressing oocytes but not in oocytes injected with
      water or JAK2 alone, the addition of leucine (2mM) to the bath generated a
      current (I(le)), which was significantly increased following coexpression of JAK2
      or (V617F)JAK2, but not by coexpression of (K882E)JAK2. Coexpression of JAK2
      enhanced the maximal transport rate without significantly modifying the affinity
      of the carrier. Exposure of the oocytes to the JAK2 inhibitor AG490 (40MUM)
      resulted in a gradual decline of I(le). According to chemiluminescence JAK2
      enhanced the carrier protein abundance in the cell membrane. The decline of I(le)
      following inhibition of carrier insertion by brefeldin A (5MUM) was similar in
      the absence and presence of JAK2 indicating that JAK2 stimulates carrier
      insertion into rather than inhibiting carrier retrival from the cell membrane. In
      conclusion, JAK2 up-regulates SLC6A19 activity which may foster amino acid uptake
      into JAK2 expressing cells.

PMID- 21964292
TI  - Restoration of autophagy by puerarin in ethanol-treated hepatocytes via the
      activation of AMP-activated protein kinase.
AB  - We investigated the effects of puerarin, the major isoflavone in Kudzu roots, on
      the regulation of autophagy in ethanol-treated hepatocytes. Incubation in ethanol
      (100 mM) for 24 h reduced cell viability by 20% and increased the cellular
      concentrations of cholesterol and triglycerides by 40% and 20%, respectively.
      Puerarin stimulation significantly recovered cell viability and reduced cellular
      lipid accumulation to a level comparable to that in untreated control cells.
      Ethanol incubation reduced autophagy significantly as assessed by microtubule
      associated protein1 light chain 3 (LC3) expression using immunohistochemistry and
      immunoblot analysis. The reduced expression of LC3 was restored by puerarin in a
      dose-dependent manner in ethanol-treated cells. The effect of puerarin on
      mammalian targets of rapamycin (mTOR), a key regulator of autophagy, was examined
      in ethanol-treated hepatocytes. Immunoblotting revealed that puerarin
      significantly induced the phosphorylation of 5'AMP-activated protein kinase
      (AMPK), thereby suppressing the mTOR target proteins S6 ribosomal protein and 4E
      binding protein 1. These data suggest that puerarin restored the viability of
      cells and reduced lipid accumulation in ethanol-treated hepatocytes by activating
      autophagy via AMPK/mTOR-mediated signaling.

PMID- 21964293
TI  - The NDUFB6 subunit of the mitochondrial respiratory chain complex I is required
      for electron transfer activity: a proof of principle study on stable and
      controlled RNA interference in human cell lines.
AB  - Molecular bases of inherited deficiencies of mitochondrial respiratory chain
      complex I are still unknown in a high proportion of patients. Among 45 subunits
      making up this large complex, more than half has unknown function(s).
      Understanding the function of these subunits would contribute to our knowledge on
      mitochondrial physiology but might also reveal that some of these subunits are
      not required for the catalytic activity of the complex. A direct consequence of
      this finding would be the reduction of the number of candidate genes to be
      sequenced in patients with decreased complex I activity. In this study, we tested
      two different methods to stably extinct complex I subunits in cultured cells. We
      first found that lentivirus-mediated shRNA expression frequently resulted in the
      unpredicted extinction of additional gene(s) beside targeted ones. This can be
      ascribed to uncontrolled genetic material insertions in the genome of the host
      cell. This approach thus appeared inappropriate to study unknown functions of a
      gene. Next, we found it possible to specifically extinct a CI subunit gene by
      direct insertion of a miR targeting CI subunits in a Flp site (HEK293 Flp-In
      cells). By using this strategy we unambiguously demonstrated that the NDUFB6
      subunit is required for complex I activity, and defined conditions suitable to
      undertake a systematic and stable extinction of the different supernumerary
      subunits in human cells.

PMID- 21964294
TI  - Sensing actin dynamics: structural basis for G-actin-sensitive nuclear import of
      MAL.
AB  - The coordination of cytoskeletal actin dynamics with gene expression
      reprogramming is emerging as a crucial mechanism to control diverse cellular
      processes, including cell migration, differentiation and neuronal circuit
      assembly. The actin-binding transcriptional coactivator MAL (also known as MRTF
      A/MKL1/BSAC) senses G-actin concentration and transduces Rho GTPase signals to
      serum response factor (SRF). MAL rapidly shuttles between the cytoplasm and the
      nucleus in unstimulated cells but Rho-induced depletion of G-actin leads to MAL
      nuclear accumulation and activation of transcription of SRF:MAL-target genes.
      Although the molecular and structural basis of actin-regulated nucleocytoplasmic
      shuttling of MAL is not understood fully, it is proposed that nuclear import of
      MAL is mediated by importin alpha/beta heterodimer, and that G-actin competes
      with importin alpha/beta for the binding to MAL. Here we present structural,
      biochemical and cell biological evidence that MAL has a classical bipartite
      nuclear localization signal (NLS) in the N-terminal 'RPEL' domain containing Arg
      Pro-X-X-X-Glu-Leu (RPEL) motifs. The NLS residues of MAL adopt an extended
      conformation and bind along the surface groove of importin-alpha, interacting
      with the major- and minor-NLS binding sites. We also present a crystal structure
      of wild-type MAL RPEL domain in complex with five G-actins. Comparison of the
      importin-alpha- and actin-complexes revealed that the binding of G-actins to MAL
      is associated with folding of NLS residues into a helical conformation that is
      inappropriate for importin-alpha recognition.

PMID- 21964295
TI  - The translation initiation factor, PeIF5B, from Pisum sativum displays chaperone
      activity.
AB  - We earlier documented the structural and functional characterization of PeIF5B
      factor from Pisum sativum that shows strong homology to the universal translation
      initiation factor eIF5B (Rasheedi et al., 2007, 2010 [12,13]). We now show that
      PeIF5B is an unusually thermo-stable protein resisting temperatures up to 95 
      degrees C. PeIF5B prevents thermal aggregation of heat labile proteins, such as
      citrate synthase (CS) and NdeI, under heat stress or chemical denaturation
      conditions and promotes their functional folding. It also prevents the
      aggregation of DTT induced insulin reduction. GTP appears to stimulate PeIF5B
      mediated chaperone activity. In-vivo, PeIF5B over expression significantly
      enhances, the viability of Escherichia coli cells after heat stress (50  degrees
      C). These observations lead us to conclude that PeIF5B, in addition to its role
      in protein translation, has chaperone like activity and could be likely involved
      in protein folding and protection from stress.

PMID- 21964296
TI  - N-butyryl-homoserine lactone, a bacterial quorum-sensing signaling molecule,
      induces intracellular calcium elevation in Arabidopsis root cells.
AB  - N-acyl-L-homoserine lactones (AHLs) are quorum sensing (QS) signal molecules that
      are commonly used in gram-negative bacteria. Recently, it has become evident that
      AHLs can influence the behavior of plant cells. However, little is known about
      the mechanism of the plants' response to these bacterial signals. Calcium ions
      (Ca(2+)), ubiquitous intracellular second messengers, play an essential role in
      numerous signal transduction pathways in plants. In this study, the cytosolic
      free Ca(2+) concentration ([Ca(2+)](cyt)) was measured by a luminometric method
      in the excised root cells of Arabidopsis plants that were treated with N-butyryl
      homoserine lactone (C4-HSL). There was a transient and immediate increase in
      [Ca(2+)](cyt) levels, and the highest level (0.4 MUM), approximately 2-fold
      higher than the basal level, was observed at the 6th second after the addition of
      10 MUM C4-HSL. Pretreatments with La(3+), verapamil or ethylene glycol
      tetraacetic acid (EGTA) inhibited the increase in [Ca(2+)](cyt) caused by C4-HSL,
      whereas it remained unaffected by pretreatment with Li(+), indicating that the
      Ca(2+) contributing to the increase in [Ca(2+)](cyt) was mobilized from the
      extracellular medium via the plasma membrane Ca(2+) channels but not from the
      intracellular Ca(2+) stores. Furthermore, electrophysiological approaches showed
      that the transmembrane Ca(2+) current was significantly increased with the
      addition of C4-HSL. Taken together, our observations suggest that C4-HSL may act
      as an elicitor from bacteria to plants and that Ca(2+) signaling participates in
      the ability of plant cells to sense the bacterial QS signals.

PMID- 21964297
TI  - Identification and function of the second eIF4E-binding region in N-terminal
      domain of eIF4G: comparison with eIF4E-binding protein.
AB  - The eukaryotic initiation factor 4E (eIF4E) serves as a master switch that
      controls mRNA translation through the promotive binding to eIF4G and the
      regulative binding with the endogenous inhibitor 4E-BP. Although the bindings of
      eIF4G and 4E-BP to eIF4E proceed through the common eIF4E recognition Y(X)(4)Lphi
      motif (X: variable, phi: hydrophobic) (first binding site), the relationship
      between their eIF4E binding mode and the functional difference is hardly known.
      Recently, we have clarified the existence and function of the second eIF4E
      binding site in 4E-BP. Surface plasmon resonance (SPR) analysis based on the
      sequential comparison between 4E-BP and eIF4GI clarified that eIF4G has the
      second binding site at the periphery of the (597)SDVVL(601) sequence and that it
      plays an auxiliary but indispensable function in stabilizing the binding of the
      first binding sequence (572)YDREFLL(578). The kinetic parameters of the
      interactions of the eIF4GI and 4E-BP2 fragment peptides with eIF4E showed that
      the association (ka) and dissociation (kd) rates of the former peptide are about
      three and two orders of magnitude lower than those of the latter peptide,
      respectively. This means that eIF4G has a potent resistive property for release
      from eIF4E, although its rate of binding to eIF4E is not as high as that of 4E
      BP, that is, 4E-BP is apt to bind to and be released from eIF4E, as compared with
      eIF4G. Isothermal titration calorimetry (ITC) showed the opposite behavior
      between the second binding sites of eIF4GI and 4E-BP for the interaction with
      eIF4E. This clearly indicates the importance of the second binding region for the
      difference in function between eIF4G and 4E-BP for eIF4E translation.

PMID- 21964298
TI  - Ciliary resorption modulates G1 length and cell cycle progression.

PMID- 21964299
TI  - A cisplatin-resistant subpopulation of mesenchymal-like cells in head and neck
      squamous cell carcinoma.

PMID- 21964300
TI  - Cardiac toxicity of 5-ring polycyclic aromatic hydrocarbons is differentially
      dependent on the aryl hydrocarbon receptor 2 isoform during zebrafish
      development.
AB  - Petroleum-derived compounds, including polycyclic aromatic hydrocarbons (PAHs),
      commonly occur as complex mixtures in the environment. Recent studies using the
      zebrafish experimental model have shown that PAHs are toxic to the embryonic
      cardiovascular system, and that the severity and nature of this developmental
      cardiotoxicity varies by individual PAH. In the present study we characterize the
      toxicity of the relatively higher molecular weight 5-ring PAHs benzo[a]pyrene
      (BaP), benzo[e]pyrene (BeP), and benzo[k]fluoranthene (BkF). While all three
      compounds target the cardiovascular system, the underlying role of the ligand
      activated aryl hydrocarbon receptor (AHR2) and the tissue-specific induction of
      the cytochrome p450 metabolic pathway (CYP1A) were distinct for each. BaP
      exposure (40MUM) produced AHR2-dependent bradycardia, pericardial edema, and
      myocardial CYP1A immunofluorescence. By contrast, BkF exposure (4-40MUM) caused
      more severe pericardial edema, looping defects, and erythrocyte regurgitation
      through the atrioventricular valve that were AHR2-independent (i.e., absent
      myocardial or endocardial CYP1A induction). Lastly, exposure to BeP (40MUM)
      yielded a low level of CYP1A+ signal in the vascular endothelium of the head and
      trunk, without evident toxic effects on cardiac function or morphogenesis.
      Combined with earlier work on 3- and 4-ring PAHs, our findings provide a more
      complete picture of how individual PAHs may drive the cardiotoxicity of mixtures
      in which they predominate. This will improve toxic injury assessments and risk
      assessments for wild fish populations that spawn in habitats altered by
      overlapping petroleum-related human impacts such as oil spills, urban stormwater
      runoff, or sediments contaminated by legacy industrial activities.

PMID- 21964301
TI  - Liposomes as an alternative delivery system for investigating dietary metal
      toxicity to Daphnia magna.
AB  - Dietary metal toxicity studies with invertebrates such as Daphnia magna are often
      performed using metal-contaminated algae as a food source. A drawback of this
      approach is that it is difficult to distinguish between the direct toxicity of
      the metal and indirect effects caused by a reduced essential nutrient content in
      the metal-contaminated diet, due to prior exposure of the algae to the metal.
      This hampers the study of the mechanisms of dietary metal toxicity in filter
      feeding freshwater invertebrates. The aim of the present study was to develop a
      technique for producing metal-contaminated liposomes as an alternative delivery
      system of dietary metals. These liposomes are not vulnerable to metal-induced
      shifts in nutrient quality. Liposomes were prepared by the hydration of
      phosphatidylcholine in media containing either 0 (control) or 50mg Ni/L. The
      liposomes had average diameters of 19.31 (control) and 10.48 MUm (Ni-laden),
      i.e., a size appropriate for ingestion by D. magna. The liposome particles were
      then mixed with uncontaminated green algae in a 1/10 ratio (on a dry wt. basis)
      to make up two diets that differed in Ni content (i.e., 2.0 MUg Ni/g dry wt. in
      the control and 144.2 MUg Ni/g dry wt. in the Ni-contaminated diet,
      respectively). This diet was then fed to D. magna during a 21-day chronic
      bioassay. The experiment showed that the Ni content and the size distribution of
      the liposomes were stable for at least 7 days. Also the use of
      phosphatidylcholine as a liposome component did not affect the reproduction of
      the daphnids. Exposure to increased level of dietary Ni resulted in 100%
      mortality after 14 days of exposure and in an increased whole-body Ni
      concentration in D. magna of 14.9 and 20.4 MUg Ni/g dry wt. after 7 and 14 days
      of exposure, respectively. The Ni-exposed daphnids also exhibited a reduced size
      (i.e., 30% smaller than the control) after 7 days and a completely halted growth
      between day 7 and day 14. In terms of reproduction, the size of the first brood
      (number of juveniles) of the Ni-exposed daphnids was significantly reduced (by
      85%) compared to the control. None of the Ni-exposed individuals were able to
      produce a second brood before dying. The algal ingestion rate - after correction
      for the indirect effect of a reduced size - was increased (by 68%) by dietary Ni
      after 6 days of exposure compared to the control, but was severely reduced (by
      80% compared to the control) after 13 days. These data suggest that an inhibition
      of the ingestion process may have contributed to the observed effects of dietary
      Ni on growth and reproduction beyond 6 days of exposure, although the involvement
      of other mechanisms cannot be excluded. The mechanism(s) which led to the reduced
      growth during the first week of exposure remain unclear, although inhibition of
      the ingestion process can likely be excluded here as an explanation. Overall,
      this paper demonstrates, using this new method of delivering dietary Ni via
      liposome carriers and thus excluding potential diet quality shifts, that dietary
      Ni can indeed induce toxic effects in D. magna. This method may therefore be a
      promising tool to help further elucidate the mechanisms of dietary metal toxicity
      to filter-feeding invertebrates.

PMID- 21964302
TI  - Sleep, epilepsy and translational research: what can we learn from the laboratory
      bench?
AB  - The relationship between sleep and epilepsy has been known since ancient times,
      and the modulating effects of both on each other have been widely described in
      clinical studies. However, the mechanisms of this correlation remain unclear.
      Translational research is essential for filling the gaps in our knowledge, and
      for developing better therapeutic approaches to improve the quality of life of
      epileptic patients. Excellent animal models of epilepsy are available for the
      investigation of various aspects of epilepsy, such as epileptogenesis and
      hippocampal sclerosis. These models also show an association between sleep and
      epilepsy, suggesting that they are suitable for translational research on this
      relationship. While some knowledge has been obtained from preclinical studies,
      the topic remains relatively unexplored. In terms of the role of sleep in
      modulating seizure susceptibility in epilepsy, animal sleep research is a major
      tool. In this review, we focus on the intricate relationship between sleep and
      epilepsy in the preclinical setting, using a translational science approach.

PMID- 21964303
TI  - Cell phones and landlines: the impact of gene therapy on the cost and
      availability of treatment for hemophilia.

PMID- 21964306
TI  - Intranasal exosomes for treatment of neuroinflammation? Prospects and
      limitations.

PMID- 21964307
TI  - Bridge over troubled stem cells.

PMID- 21964308
TI  - Mutational profiling of sporadic versus toxin-associated brain cancer formation:
      initial findings using loss of heterozygosity profiling.
AB  - The role of environmental and occupational toxin exposure as a cause of or
      contributing factor for cancer development and progression is incompletely
      understood. A unique signature of specific mutational change to discriminate
      toxin-exposed from sporadic cancer is generally sought but not often encountered.
      We report an approach to better understand cancer causality based on the
      measurement of the cumulative DNA damage (via loss of heterozygosity) over a
      defined genomic region (chromosome 3) that is applicable to archival, fixative
      treated tissue and cytology specimens of cancer. Our method was applied to (1) a
      cohort of 10 brain tumor subjects (9 gliomas, 1 hemangioblastoma) with potential
      exposure to chlorinated solvents and (2) a control cohort of sporadic brain
      cancer controls (7 gliomas, 1 hemangioblastoma). We show that brain tumors
      arising in potentially toxin-exposed subjects bear a significantly higher level
      of passenger LOH mutations compared to sporadic cancer controls. The methodology
      utilized tissue microdissection, PCR amplification and capillary electrophoresis
      (fragment analysis for LOH determination, DNA sequencing for specific point
      mutations), and examined a panel of 15 microsatellite markers distributed along
      both arms of chromosome 3 that aimed at capturing passenger mutational change
      accrued during stages of clonal expansion of neoplastic cells. This proof-of
      principle study using mutational profiling for passenger LOH mutational damage
      provides support for the utility of this approach and further studies in order to
      differentiate between genotoxin-associated versus sporadic (unexposed) cancer
      development.

PMID- 21964309
TI  - Human biomonitoring for metals in Italian urban adolescents: data from Latium
      Region.
AB  - As a part of the activities of the first Italian human biomonitoring survey
      (PROBE - PROgramme for Biomonitoring general population Exposure), a reference
      population of adolescents, aged 13-15 years, was examined for their exposure to
      metals. The study included 252 adolescents living in urban areas, representative
      of Latium Region (Italy) and blood specimens were analyzed for metals (As, Be,
      Cd, Co, Cr, Hg, Ir, Mn, Mo, Ni, Pb, Pd, Pt, Rh, Sb, Sn, Tl, U, V and W) by sector
      field inductively coupled plasma mass spectrometry. The results obtained will
      improve the knowledge about the body burden in adolescents and are tentative
      reference values for Italian young people as a basis for risk evaluation deriving
      from urban/environmental exposure to metals.

PMID- 21964311
TI  - Lattice contracted AgPt nanoparticles.
AB  - Lattice distortion in AgPt nanoparticles was studied using X-ray diffraction and
      other techniques. These nanoparticles show high catalytic activity in the
      reduction of p-nitrophenol and had a turn over frequency of 5.4 * 10(2) s(-1).

PMID- 21964312
TI  - The case for wider use of recombinant factor VIII concentrates.
AB  - The introduction of clotting factor concentrates led to major advances in
      hemophilia care. Rather than simply providing an alternative to plasma-derived
      concentrates, the introduction in the 1990s of recombinant concentrates added
      value to replacement therapy particularly with respect to prophylaxis and immune
      tolerance induction. While the safety of plasma-derived concentrates has improved
      considerably, these concentrates may still pose an infectious risk through as-yet
      unknown pathogens and poor impurity constituent characterization. Recombinant
      concentrates are increasingly used because of their benefits in pathogen safety,
      convenience and the potential for unfettered supply. Yet worldwide they remain
      accessible only to a limited number of patients due to fear of the potential for
      inhibitor development, overestimation of their costs and underestimation of their
      benefits. This article reviews the characteristics and properties of recombinant
      FVIII concentrates to help physicians and patient representatives promote the
      right of access of patients to the safest products.

PMID- 21964310
TI  - Differential synthesis and action of TGFbeta superfamily ligands in mouse and rat
      islets.
AB  - Members of the TGFbeta superfamily, including activins and TGFbeta, modulate
      glucose-stimulated insulin secretion (GSIS) in vitro using rat islets while
      genetic manipulations that reduce TGFbeta superfamily signaling in vivo in mice
      produced hypoplastic islets and/or hyperglycemia. Moreover, deletion of Fstl3, an
      antagonist of activin and myostatin, resulted in enlarged islets and beta-cell
      hyperplasia. These studies suggest that endogenous TGFbeta superfamily ligands
      regulate beta-cell generation and/or function. To test this hypothesis, we
      examined endogenous TGFbeta ligand synthesis and action in isolated rat and mouse
      islets. We found that activin A, TGFbeta1, and myostatin treatment enhanced rat
      islet GSIS but none of the ligands tested enhanced GSIS in mouse islets. However,
      follistatin inhibited GSIS, consistent with a role for endogenous TGFbeta
      superfamily ligands in regulating insulin secretion. Endogenous expression of
      TGFbeta superfamily members was different in rat and mouse islets with myostatin
      being highly expressed in mouse islets and not detectable in rats. These results
      indicate that TGFbeta superfamily members directly regulate islet function in a
      species-specific manner while the ligands produced by islets differ between mice
      and rats. The lack of in vitro actions of ligands on mouse islets may be
      mechanical or result from species-specific actions of these ligands.

PMID- 21964313
TI  - Molecular cloning, expression analysis and characterization of peroxiredoxin
      during WSSV infection in shrimp Fenneropenaeus indicus.
AB  - Innate immunity is the first line of defense in shrimps against invading
      pathogenic microorganisms. Peroxiredoxins (PRX) are the family of antioxidant
      proteins that play a crucial role in reduction of oxidative stress in host during
      viral infection. Peroxiredoxin from Fenneropenaeus indicus was identified, cloned
      and expressed in prokaryotic expression system. The Fi-PRX protein consists of
      two conserved Cys residues and belongs to typical 2-cys PRX family. The
      phylogenetic analysis revealed a close evolutionary relatedness of Fi-PRX with
      the PRX from Drosophila melanogaster PRX1 and distant origin with PRX sequences
      from other shrimp isolates Fenneropenaeus chinensis, Litopenaeus vannamei and
      Penaeus japonicus. Fi-PRX transcripts are constitutively expressed in hemocytes
      and tissues (gills, heart and muscle) and down regulated during 12 h, 24 h and 48
      h of WSSV challenged shrimps. Fi-PRX protein levels correlated well with the
      corresponding levels of Fi-PRX transcripts in hemocytes and tissues of WSSV
      challenged shrimps. Recombinant Fi-PRX reduces insulin only in the presence of
      DTT suggesting that the antioxidant function of the protein is thiol dependent.
      These findings suggest that antioxidant activity of Fi-PRX play a significant
      role in neutralization of excessive free radicals and ROS generated during viral
      invasion.

PMID- 21964314
TI  - Id3 upregulates BrdU incorporation associated with a DNA damage response, not
      replication, in human pancreatic beta-cells.
AB  - Elucidating mechanisms of cell cycle control in normally quiescent human
      pancreatic beta-cells has the potential to impact regeneration strategies for
      diabetes. Previously we demonstrated that Id3, a repressor of basic Helix-Loop
      Helix (bHLH) proteins, was sufficient to induce cell cycle entry in pancreatic
      duct cells, which are closely related to beta-cells developmentally. We
      hypothesized that Id3 might similarly induce cell cycle entry in primary human
      beta-cells. To test this directly, adult human beta-cells were transduced with
      adenovirus expressing Id3. Consistent with a replicative response, beta-cells
      exhibited BrdU incorporation. Further, Id3 potently repressed expression of the
      cyclin dependent kinase inhibitor p57 (Kip2 ) , a gene which is also silenced in
      a rare beta-cell hyperproliferative disorder in infants. Surprisingly however,
      BrdU positive beta-cells did not express the proliferation markers Ki67 and pHH3.
      Instead, BrdU uptake reflected a DNA damage response, as manifested by
      hydroxyurea incorporation, gammaH2AX expression, and 53BP1 subcellular
      relocalization. The uncoupling of BrdU uptake from replication raises a
      cautionary note about interpreting studies relying solely upon BrdU incorporation
      as evidence of beta-cell proliferation. The data also establish that loss of p57
      (Kip2) is not sufficient to induce cell cycle entry in adult beta-cells.
      Moreover, the differential responses to Id3 between duct and beta-cells reveal
      that beta-cells possess intrinsic resistance to cell cycle entry not common to
      all quiescent epithelial cells in the adult human pancreas. The data provide a
      much needed comparative model for investigating the molecular basis for this
      resistance in order to develop a strategy for improving replication competence in
      beta-cells.

PMID- 21964315
TI  - Anthrax sub-unit vaccine: the structural consequences of binding rPA83 to
      Alhydrogel(r).
AB  - An anthrax sub-unit vaccine, comprising recombinant Protective Antigen (rPA83)
      and aluminium hydroxide adjuvant (Alhydrogel(r)) is currently being developed.
      Here, a series of biophysical techniques have been applied to free and adjuvant
      bound antigen. Limited proteolysis and fluorescence identified no changes in
      rPA83 tertiary structure following binding to Alhydrogel and the bound rPA83
      retained two structurally important calcium ions. For adsorbed rPA83,
      differential scanning calorimetry revealed a small reduction in unfolding
      temperature but a large decrease in unfolding enthalpy whilst urea unfolding
      demonstrated unchanged stability but a loss of co-operativity. Overall, these
      results demonstrate that interactions between rPA83 and Alhydrogel have a minimal
      effect on the folded protein structure and suggest that antigen destabilisation
      is not a primary mechanism of Alhydrogel adjuvancy. This study also shows that
      informative structural characterisation is possible for adjuvant bound sub-unit
      vaccines.

PMID- 21964316
TI  - Thiolated chitosan: development and in vivo evaluation of an oral delivery system
      for leuprolide.
AB  - The aim of the present study was to develop an oral delivery system for the
      peptide drug leuprolide. Gel formulations based on unmodified chitosan/reduced
      glutathione (GSH) and chitosan-thioglycolic acid (chitosan-TGA)/GSH were
      prepared, and their effect on the absorption of leuprolide was evaluated in vitro
      and in vivo in male Sprague Dawley rats. Transport studies were performed with
      freshly excised rat intestinal mucosa mounted in Ussing-type chambers. Due to the
      addition of gel formulations comprising 0.5% (m/v) unmodified chitosan/0.5% (m/v)
      GSH and 0.5% (m/v) chitosan-TGA/0.5% (m/v) GSH, the transport of leuprolide
      across excised mucosa was improved up to 2.06-fold and 3.79-fold, respectively,
      in comparison with leuprolide applied in buffer (P(app)=2.87 +/- 0.77 * 10-6
      cm/s). In vivo, the addition of oral gel formulation comprising 8 mg of
      unmodified chitosan, 1mg of GSH and 1mg of leuprolide increased the area under
      the plasma concentration-time curve (AUC0-8) of leuprolide 1.39-fold in
      comparison with leuprolide having been administered just in saline. Moreover, the
      administration of oral gel formulation comprising 8 mg of chitosan-TGA, 1mg of
      GSH and 1mg of leuprolide resulted in a further enhanced leuprolide plasma
      concentration, and the area under the plasma concentration-time curve (AUC0-8) of
      leuprolide was increased 3.72-fold in comparison with the control. With the oral
      gel formulation comprising 8 mg of chitosan-TGA, a relative bioavailability
      (versus s.c. injection) of 4.5% was achieved in contrast to the control
      displaying a relative bioavailability of 1.2%. Thus, according to the achieved
      results, it is suggested that chitosan-TGA in combination with GSH is a valuable
      tool for improving the oral bioavailability of the peptide drug leuprolide.

PMID- 21964317
TI  - Photocrosslinked poly(ester anhydride)s for peptide delivery: Effect of oligomer
      hydrophobicity on PYY3-36 delivery.
AB  - The treatment for many diseases can be improved by developing more efficient
      peptide delivery technologies, for example, biodegradable polymers. In this work,
      photocrosslinked poly(ester anhydride)s based on functionalized poly(epsilon
      caprolactone) oligomers were investigated for their abilities to achieve
      controlled peptide delivery. The effect of oligomer hydrophobicity on erosion and
      peptide release from poly(ester anhydride)s was evaluated by developing a
      sustained subcutaneous delivery system for an antiobesity drug candidate, peptide
      YY3-36 (PYY3-36). Oligomer hydrophobicity was modified with alkenylsuccinic
      anhydrides containing a 12-carbon alkenyl chain. PYY3-36 was mixed as a solid
      powder with methacrylated poly(ester anhydride) precursors, and this mixture was
      photocrosslinked at room temperature to form an implant for subcutaneous
      administration in rats. The oligomer hydrophobicity controlled the polymer
      erosion and PYY3-36 release as the increased hydrophobicity via the alkenyl chain
      prolonged polymer erosion in vitro and sustained in vivo release of PYY3-36. In
      addition, photocrosslinked poly(ester anhydride)s increased the bioavailability
      of PYY3-36 by up to 20-fold in comparison with subcutaneous administration of
      solution, evidence of remarkably improved delivery. In conclusion, this work
      demonstrates the suitability of photocrosslinked poly(ester anhydride)s for use
      in peptide delivery.

PMID- 21964318
TI  - Estrogen dependent signaling in reproductive tissues - a role for estrogen
      receptors and estrogen related receptors.
AB  - Estrogens play a fundamental role in the development and normal physiological
      function of multiple tissue systems and have been implicated in the ontogeny of
      cancers. The biological effects of estrogens are classically mediated via
      interaction with cognate nuclear receptors. The relative expression of ER
      subtypes/variants varies between cells within different tissues and this alters
      the response to natural and synthetic ligands. This review focuses on the role of
      estrogen and estrogen related receptors in reproductive tissues.

PMID- 21964319
TI  - Mammalian ovary differentiation - a focus on female meiosis.
AB  - Over the past 50 years, the ovary development has been subject of fewer studies
      as compare to the male pathway. Nevertheless due to the advancement of genetics,
      mouse ES cells and the development of genetic models, studies of ovarian
      differentiation was boosted. This review emphasizes some of new progresses in the
      research field of the mammalian ovary differentiation that have occurred in
      recent years with focuses of the period around prophase I of meiosis and of
      recent roles of small non-RNAs in the ovarian gene expression.

PMID- 21964320
TI  - Green tea polyphenols produce antidepressant-like effects in adult mice.
AB  - Recent studies have shown that a higher consumption of green tea leads to a lower
      prevalence of depressive symptoms in elderly individuals. However, no studies
      have explored the antidepressant-like effect of green tea in preclinical models
      of depression. The aim of this study was to investigate the antidepressant-like
      effects and the possible mechanism of action of green tea in widely used mouse
      models of depression. Mice were orally administered green tea polyphenols (GTP;
      5, 10 and 20mg/kg) for 7days and assessed in the forced swimming test (FST) and
      tail suspension test (TST) 60min after the last GTP administration. Serum
      corticosterone and adrenocorticotrophic hormone (ACTH) levels were also
      determined immediately after the FST. Green tea polyphenols significantly reduced
      immobility in both the FST and TST but did not alter locomotor activity in the
      open field test, suggesting that GTP has antidepressant-like effects, and this
      action did not induce nonspecific motor changes in mice. Green tea polyphenols
      also reduced serum corticosterone and ACTH levels in mice exposed to the FST. The
      present study demonstrated that GTP exerts antidepressant-like effects in a mouse
      behavioral models of depression, and the mechanism may involve inhibition of the
      hypothalamic-pituitary-adrenal axis.

PMID- 21964321
TI  - Effects of copper on the acute cortisol response and associated physiology in
      rainbow trout.
AB  - The aim of this study was to determine the effects of chronic waterborne copper
      (Cu) exposure on the acute stress-induced cortisol response and associated
      physiological consequences in rainbow trout (Oncorhynchus mykiss). Trout were
      exposed to 30 MUg Cu/L in moderately hard water (120 mg/L as CaCO(3)) for 40
      days, following which time the acute cortisol response was examined with a series
      of stressors. At 40 days, a 65% increase in Cu was observed in the gill, but no
      accumulation was observed in the liver, brain or head kidney. Stressors such as
      air exposure or confinement did not elicit an increase in circulating cortisol
      levels for Cu-exposed fish, in contrast to controls. However, this inhibitory
      effect on the acute cortisol response appeared to have few implications on the
      ability of Cu-exposed fish to maintain ion and carbohydrate homeostasis. For
      example, plasma Na(+), Ca(2+) and glucose levels as well as hepatic glycogen
      levels were the same post-stress in control and Cu-exposed fish. Trout were also
      challenged with exposure to 50% seawater for 48 h, where Cu-exposed trout
      maintained plasma Na(+), glucose and hepatic glycogen levels. However, Cu-exposed
      fish experienced decreased plasma K(+) levels throughout the Cu exposure and
      stress tests. In conclusion, chronic Cu exposure resulted in the abolition of an
      acute cortisol response post-stress. There was no Cu accumulation in the
      hypothalamus-pituitary-interrenal axis (HPI axis) suggesting this was not a
      direct toxic effect of Cu on the cortisol regulatory pathway. However, the lack
      of an acute cortisol response in Cu-exposed fish did not impair the ability of
      the fish to maintain ion and carbohydrate homeostasis. This effect on cortisol
      may be a strategy to reduce costs during the chronic stress of Cu exposure, and
      not endocrine disruption as a result of toxic injury.

PMID- 21964322
TI  - N-cadherin adherens junctions mediate osteogenesis through PI3K signaling.
AB  - During endochondral ossification, the cartilage is surrounded by a layer of cells
      that constitute the perichondrium. Communication between osteoblasts in the
      perichondrium via N-cadherin adherens junctions is essential for endochondral
      bone growth. We observed that adherens junction molecule N-cadherin and its
      interacting partners p120, beta-catenin and PTEN are expressed by cells present
      in the perichondrium. To study if N-cadherin mediated adherens junctions play a
      role in mediating signal transduction events during bone development, we utilized
      MC3T3E1 preosteoblasts plated at sub confluent (low) and confluent (high)
      densities to mimic adherens junction formation. When MC3T3E1 cells were plated at
      high density we observed an increase in phosphorylation of AKTSer473 and its
      downstream target GSK3Ser9, which coincided with an increase in Osterix,
      Osteomodulin and Osteoglycin gene expression. Using immunofluorescence, we
      identified N-cadherin, p120 and beta-catenin localized at the membrane of MC3T3E1
      cells. Treatment of confluent MC3T3E1 cells with an N-cadherin junction inhibitor
      EGTA and a PI3K inhibitor LY294002 resulted in reduction of phosphorylation
      levels of AKT and GSK3 and expression of Osterix, Osteomodulin and Osteoglycin.
      Furthermore, utilizing an N-cadherin blocking antibody resulted in reduced AKT
      signaling and Osterix gene expression, suggesting that osteoblast junction
      formation is linked to activation of PI3K signaling, which leads to osteoblast
      differentiation. To further explore the strength of this linkage, we utilized a
      conditional knockout approach using Dermo1cre to delete beta-catenin and PTEN,
      two important proteins known to be essential for adherens junctions and PI3K
      signaling, respectively. In the absence of beta-catenin, we observed a decrease
      in adherens junctions and AKT signaling in the perichondrium. PTEN deletion, on
      the other hand, increased the number of cells expressing N-cadherin in the
      perichondrium. These observations show that N-cadherin mediated junctions between
      osteoblasts are needed for osteoblast gene transcription.

PMID- 21964323
TI  - JNK inhibitors increase osteogenesis in Nf1-deficient cells.
AB  - Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder that is
      associated with a variety of manifestations, including orthopedic complications
      such as scoliosis and tibial pseudarthrosis. Orthopedic management of these
      skeletal complications is rendered more challenging due to a lack of standardized
      adjunctive pharmacotherapies. NF1 leads to disruption of the canonical Ras/Raf
      1/MEK/ERK axis, and this has been associated with defects in bone anabolism. The
      roles of other non-canonical Ras effector pathways, such as the c-Jun N-terminal
      Kinase (JNK) pathway, are less well understood. In this study we examine the
      effects of an anthrapyrazolone inhibitor of JNK (SP600125) on inducible
      osteoprogenitors as well as Nf1-deficient and Nf1-null primary osteoblasts. C2C12
      cells, which are highly responsive to rhBMP-2, were examined with exogenous rhBMP
      2 and a range of SP600125 doses. Based on the expression of early and late bone
      markers and matrix mineralization, 10 MUM SP600125 was found to be pro-osteogenic
      whether delivered concurrent with or following 2 days of rhBMP-2 treatment.
      Aberrant JNK activity was identified in Nf1-deficient osteoprogenitors (increased
      rhBMP-2 induced phospho-c-Jun) and in Nf1-null mature osteoblasts (increased
      total c-Jun). Next, SP600125 was used to treat these cells and was found to
      facilitate osteogenesis in Nf1-deficient osteoprogenitors, and in Nf1-null
      osteoblasts when given in conjunction with rhBMP-2. Outcome measures included
      alkaline phosphatase activity, matrix mineralization, and osteogenic gene
      expression. In summary, JNK inhibitors represent a class of potentially useful
      adjunctive agents for orthopedic medicine, particularly in the context of NF1.

PMID- 21964324
TI  - Drug challenge with sodium-channel blockade: improving phenotypic
      characterization of early repolarization.

PMID- 21964325
TI  - Perinatal intermittent hypoxia alters gamma-aminobutyric acid: a receptor levels
      in rat cerebellum.
AB  - Perinatal hypoxia commonly causes brain injury in infants, but the time course
      and mechanisms underlying the preferential male injury are unclear. Intermittent
      hypoxia disturbs cerebellar gamma-aminobutyric (GABA)-A receptor profiles during
      the perinatal period, possibly responding to transient excitatory processes
      associated with GABA(A) receptors. We examined whether hypoxic insults were
      particularly damaging to the male rodent cerebellum during a specific
      developmental time window. We evaluated cerebellar injury and GABA(A) receptor
      profiles following 5-h intermittent hypoxia (IH: 20.8% and 10.3% ambient oxygen,
      switched every 240s) or room-air control in groups of male and female rat pups on
      postnatal d 1-2, wk 1, or wk 3. The cerebella were harvested and compared between
      groups. The mRNA levels of GABA(A) receptors alpha6, normalized to a house
      keeping gene GAPDH, and assessed using real-time reverse-transcriptase PCR assays
      were up-regulated by IH at wk 1, more extensively in male rats, with sex
      influencing the regulatory time-course. In contrast, GABA(A) alpha6 receptor
      protein expression levels, assessed using Western blot assays, reached a nadir at
      wk 1 in both male and female rats, possibly indicating involvement of a post
      transcriptional mechanism. The extent of cerebellar damage and level of
      apoptosis, assessed by DNA fragmentation, were greatest in the wk 3 IH-exposed
      group. The findings suggest partial protection for female rats against early
      hypoxic insult in the cerebellum, and that down-regulation of GABA(A) receptors,
      rather than direct neural injury assessed by DNA fragmentation may modify
      cerebellar function, with potential later motor and other deficits.

PMID- 21964326
TI  - Maternal alpha-linolenic acid availability during gestation and lactation alters
      the postnatal hippocampal development in the mouse offspring.
AB  - The availability of omega-3 polyunsaturated fatty acids is essential for
      perinatal brain development. While the roles of docosahexaenoic acid (the most
      abundant omega-3 species) were extensively described, less is known about the
      role of alpha-linolenic acid (ALA), which is the initial molecular species
      undergoing elongation and desaturation within the omega-3 pathways. This study
      describes the association between maternal ALA availability during gestation and
      lactation, and alterations in hippocampal development (dentate gyrus) in the
      mouse male offspring, at the end of lactation (postnatal day 19, P19). Postnatal
      ALA supplementation increased cell proliferation (36% more proliferating cells
      compared to a control group) and early neuronal differentiation, while postnatal
      ALA deficiency increased cellular apoptosis within the dentate gyrus of suckling
      pups (61% more apoptotic cells compared to a control group). However, maternal
      ALA deficiency during gestation prevented the increased neurogenesis induced by
      postnatal supplementation. Fatty acid analysis revealed that ALA supplementation
      increased the concentration of the omega-3 species in the maternal liver and
      serum, but not in the brain of the offspring, excepting for ALA itself.
      Interestingly, ALA supplementation also increased the concentration of dihomo
      gamma-linolenic acid (a omega-6 species) in the P19 brains, but not in maternal
      livers or serum. In conclusion, postnatal ALA supplementation enhances
      neurogenesis in the dentate gyrus of the offspring at postnatal day 19, but its
      beneficial effects are offset by maternal ALA deficiency during gestation. These
      results suggest that ALA is required in both fetal and postnatal stages of brain
      development.

PMID- 21964327
TI  - Effects of load on the guidance of visual attention from working memory.
AB  - An active recent line of research on working memory and attention has shown that
      the visual attention can be top-down guided by working memory contents. The
      present study examined whether the guidance effect is modulated by memory load,
      i.e., the amount of information maintained in working memory. In a set of three
      experiments, participants were asked to perform a visual search task while
      maintaining several objects in working memory. The memory-driven attentional
      guidance effect was observed in all experiments when there were spare working
      memory resources. When memory load was increased from one item to two items,
      there was no sign that the guidance effect was attenuated. When load was further
      increased to four items, the guidance effect disappeared completely, indicating a
      clear impact of memory load on attentional guidance.

PMID- 21964328
TI  - The role of WRKY transcription factors in plant abiotic stresses.
AB  - The WRKY gene family has been suggested to play important roles in the regulation
      of transcriptional reprogramming associated with plant stress responses.
      Modification of the expression patterns of WRKY genes and/or changes in their
      activity contribute to the elaboration of various signaling pathways and
      regulatory networks. Furthermore, a single WRKY gene often responds to several
      stress factors, and then their proteins may participate in the regulation of
      several seemingly disparate processes as negative or positive regulators. WRKY
      proteins also function via protein-protein interaction and autoregulation or
      cross-regulation is extensively recorded among WRKY genes, which help us
      understand the complex mechanisms of signaling and transcriptional reprogramming
      controlled by WRKY proteins. Here, we review recent progress made in starting to
      reveal the role of WRKY transcription factors in plant abiotic stresses. This
      article is part of a Special Issue entitled: Plant gene regulation in response to
      abiotic stress.

PMID- 21964329
TI  - Molecular mechanism of anaerobic ammonium oxidation.
AB  - Two distinct microbial processes, denitrification and anaerobic ammonium
      oxidation (anammox), are responsible for the release of fixed nitrogen as
      dinitrogen gas (N(2)) to the atmosphere. Denitrification has been studied for
      over 100 years and its intermediates and enzymes are well known. Even though
      anammox is a key biogeochemical process of equal importance, its molecular
      mechanism is unknown, but it was proposed to proceed through hydrazine
      (N(2)H(4)). Here we show that N(2)H(4) is produced from the anammox substrates
      ammonium and nitrite and that nitric oxide (NO) is the direct precursor of
      N(2)H(4). We resolved the genes and proteins central to anammox metabolism and
      purified the key enzymes that catalyse N(2)H(4) synthesis and its oxidation to
      N(2). These results present a new biochemical reaction forging an N-N bond and
      fill a lacuna in our understanding of the biochemical synthesis of the N(2) in
      the atmosphere. Furthermore, they reinforce the role of nitric oxide in the
      evolution of the nitrogen cycle.

PMID- 21964330
TI  - S-nitrosylation of NADPH oxidase regulates cell death in plant immunity.
AB  - Changes in redox status are a conspicuous feature of immune responses in a
      variety of eukaryotes, but the associated signalling mechanisms are not well
      understood. In plants, attempted microbial infection triggers the rapid synthesis
      of nitric oxide and a parallel accumulation of reactive oxygen intermediates, the
      latter generated by NADPH oxidases related to those responsible for the pathogen
      activated respiratory burst in phagocytes. Both nitric oxide and reactive oxygen
      intermediates have been implicated in controlling the hypersensitive response, a
      programmed execution of plant cells at sites of attempted infection. However, the
      molecular mechanisms that underpin their function and coordinate their synthesis
      are unknown. Here we show genetic evidence that increases in cysteine thiols
      modified using nitric oxide, termed S-nitrosothiols, facilitate the
      hypersensitive response in the absence of the cell death agonist salicylic acid
      and the synthesis of reactive oxygen intermediates. Surprisingly, when
      concentrations of S-nitrosothiols were high, nitric oxide function also governed
      a negative feedback loop limiting the hypersensitive response, mediated by S
      nitrosylation of the NADPH oxidase, AtRBOHD, at Cys 890, abolishing its ability
      to synthesize reactive oxygen intermediates. Accordingly, mutation of Cys 890
      compromised S-nitrosothiol-mediated control of AtRBOHD activity, perturbing the
      magnitude of cell death development. This cysteine is evolutionarily conserved
      and specifically S-nitrosylated in both human and fly NADPH oxidase, suggesting
      that this mechanism may govern immune responses in both plants and animals.

PMID- 21964331
TI  - An olfactory receptor for food-derived odours promotes male courtship in
      Drosophila.
AB  - Many animals attract mating partners through the release of volatile sex
      pheromones, which can convey information on the species, gender and receptivity
      of the sender to induce innate courtship and mating behaviours by the receiver.
      Male Drosophila melanogaster fruitflies display stereotyped reproductive
      behaviours towards females, and these behaviours are controlled by the neural
      circuitry expressing male-specific isoforms of the transcription factor Fruitless
      (FRU(M)). However, the volatile pheromone ligands, receptors and olfactory
      sensory neurons (OSNs) that promote male courtship have not been identified in
      this important model organism. Here we describe a novel courtship function of
      Ionotropic receptor 84a (IR84a), which is a member of the chemosensory ionotropic
      glutamate receptor family, in a previously uncharacterized population of FRU(M)
      positive OSNs. IR84a-expressing neurons are activated not by fly-derived
      chemicals but by the aromatic odours phenylacetic acid and phenylacetaldehyde,
      which are widely found in fruit and other plant tissues that serve as food
      sources and oviposition sites for drosophilid flies. Mutation of Ir84a abolishes
      both odour-evoked and spontaneous electrophysiological activity in these neurons
      and markedly reduces male courtship behaviour. Conversely, male courtship is
      increased--in an IR84a-dependent manner--in the presence of phenylacetic acid but
      not in the presence of another fruit odour that does not activate IR84a.
      Interneurons downstream of IR84a-expressing OSNs innervate a pheromone-processing
      centre in the brain. Whereas IR84a orthologues and phenylacetic-acid-responsive
      neurons are present in diverse drosophilid species, IR84a is absent from insects
      that rely on long-range sex pheromones. Our results suggest a model in which
      IR84a couples food presence to the activation of the fru(M) courtship circuitry
      in fruitflies. These findings reveal an unusual but effective evolutionary
      solution to coordinate feeding and oviposition site selection with reproductive
      behaviours through a specific sensory pathway.

PMID- 21964332
TI  - DNA stretching by bacterial initiators promotes replication origin opening.
AB  - Many replication initiators form higher-order oligomers that process host
      replication origins to promote replisome formation. In addition to dedicated
      duplex-DNA-binding domains, cellular initiators possess AAA+ (ATPases associated
      with various cellular activities) elements that drive functions ranging from
      protein assembly to origin recognition. In bacteria, the AAA+ domain of the
      initiator DnaA has been proposed to assist in single-stranded DNA formation
      during origin melting. Here we show crystallographically and in solution that the
      ATP-dependent assembly of Aquifex aeolicus DnaA into a spiral oligomer creates a
      continuous surface that allows successive AAA+ domains to bind and extend single
      stranded DNA segments. The mechanism of binding is unexpectedly similar to that
      of RecA, a homologous recombination factor, but it differs in that DnaA promotes
      a nucleic acid conformation that prevents pairing of a complementary strand.
      These findings, combined with strand-displacement assays, indicate that DnaA
      opens replication origins by a direct ATP-dependent stretching mechanism.
      Comparative studies reveal notable commonalities between the approach used by
      DnaA to engage DNA substrates and other, nucleic-acid-dependent, AAA+ systems.

PMID- 21964334
TI  - CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing.
AB  - Alternative splicing of pre-messenger RNA is a key feature of transcriptome
      expansion in eukaryotic cells, yet its regulation is poorly understood.
      Spliceosome assembly occurs co-transcriptionally, raising the possibility that
      DNA structure may directly influence alternative splicing. Supporting such an
      association, recent reports have identified distinct histone methylation
      patterns, elevated nucleosome occupancy and enriched DNA methylation at exons
      relative to introns. Moreover, the rate of transcription elongation has been
      linked to alternative splicing. Here we provide the first evidence that a DNA
      binding protein, CCCTC-binding factor (CTCF), can promote inclusion of weak
      upstream exons by mediating local RNA polymerase II pausing both in a mammalian
      model system for alternative splicing, CD45, and genome-wide. We further show
      that CTCF binding to CD45 exon 5 is inhibited by DNA methylation, leading to
      reciprocal effects on exon 5 inclusion. These findings provide a mechanistic
      basis for developmental regulation of splicing outcome through heritable
      epigenetic marks.

PMID- 21964335
TI  - Primary motor cortex underlies multi-joint integration for fast feedback control.
AB  - A basic difficulty for the nervous system is integrating locally ambiguous
      sensory information to form accurate perceptions about the outside world. This
      local-to-global problem is also fundamental to motor control of the arm, because
      complex mechanical interactions between shoulder and elbow allow a particular
      amount of motion at one joint to arise from an infinite combination of shoulder
      and elbow torques. Here we show, in humans and rhesus monkeys, that a
      transcortical pathway through primary motor cortex (M1) resolves this ambiguity
      during fast feedback control. We demonstrate that single M1 neurons of behaving
      monkeys can integrate shoulder and elbow motion information into motor commands
      that appropriately counter the underlying torque within about 50 milliseconds of
      a mechanical perturbation. Moreover, we reveal a causal link between M1
      processing and multi-joint integration in humans by showing that shoulder muscle
      responses occurring ~50 milliseconds after pure elbow displacement can be
      potentiated by transcranial magnetic stimulation. Taken together, our results
      show that transcortical processing through M1 permits feedback responses to
      express a level of sophistication that rivals voluntary control; this provides
      neurophysiological support for influential theories positing that voluntary
      movement is generated by the intelligent manipulation of sensory feedback.

PMID- 21964337
TI  - Unprecedented Arctic ozone loss in 2011.
AB  - Chemical ozone destruction occurs over both polar regions in local winter-spring.
      In the Antarctic, essentially complete removal of lower-stratospheric ozone
      currently results in an ozone hole every year, whereas in the Arctic, ozone loss
      is highly variable and has until now been much more limited. Here we demonstrate
      that chemical ozone destruction over the Arctic in early 2011 was--for the first
      time in the observational record--comparable to that in the Antarctic ozone hole.
      Unusually long-lasting cold conditions in the Arctic lower stratosphere led to
      persistent enhancement in ozone-destroying forms of chlorine and to unprecedented
      ozone loss, which exceeded 80 per cent over 18-20 kilometres altitude. Our
      results show that Arctic ozone holes are possible even with temperatures much
      milder than those in the Antarctic. We cannot at present predict when such severe
      Arctic ozone depletion may be matched or exceeded.

PMID- 21964338
TI  - Extrasolar planets: Homing in on another Earth.

PMID- 21964339
TI  - Theta-paced flickering between place-cell maps in the hippocampus.
AB  - The ability to recall discrete memories is thought to depend on the formation of
      attractor states in recurrent neural networks. In such networks, representations
      can be reactivated reliably from subsets of the cues that were present when the
      memory was encoded, at the same time as interference from competing
      representations is minimized. Theoretical studies have pointed to the recurrent
      CA3 system of the hippocampus as a possible attractor network. Consistent with
      predictions from these studies, experiments have shown that place representations
      in CA3 and downstream CA1 tolerate small changes in the configuration of the
      environment but switch to uncorrelated representations when dissimilarities
      become larger. However, the kinetics supporting such network transitions, at the
      subsecond timescale, is poorly understood. Here we show in rats that
      instantaneous transformation of the spatial context does not change the
      hippocampal representation all at once but is followed by temporary bistability
      in the discharge activity of CA3 ensembles. Rather than sliding through a
      continuum of intermediate activity states, the CA3 network undergoes a short
      period of competitive flickering between preformed representations of the past
      and present environment before settling on the latter. Network flickers are
      extremely fast, often with complete replacement of the active ensemble from one
      theta cycle to the next. Within individual cycles, segregation is stronger
      towards the end, when firing starts to decline, pointing to the theta cycle as a
      temporal unit for expression of attractor states in the hippocampus. Repetition
      of pattern-completion processes across successive theta cycles may facilitate
      error correction and enhance discriminative power in the presence of weak and
      ambiguous input cues.

PMID- 21964340
TI  - Inhibition of BET recruitment to chromatin as an effective treatment for MLL
      fusion leukaemia.
AB  - Recurrent chromosomal translocations involving the mixed lineage leukaemia (MLL)
      gene initiate aggressive forms of leukaemia, which are often refractory to
      conventional therapies. Many MLL-fusion partners are members of the super
      elongation complex (SEC), a critical regulator of transcriptional elongation,
      suggesting that aberrant control of this process has an important role in
      leukaemia induction. Here we use a global proteomic strategy to demonstrate that
      MLL fusions, as part of SEC and the polymerase-associated factor complex (PAFc),
      are associated with the BET family of acetyl-lysine recognizing, chromatin
      'adaptor' proteins. These data provided the basis for therapeutic intervention in
      MLL-fusion leukaemia, via the displacement of the BET family of proteins from
      chromatin. We show that a novel small molecule inhibitor of the BET family,
      GSK1210151A (I-BET151), has profound efficacy against human and murine MLL-fusion
      leukaemic cell lines, through the induction of early cell cycle arrest and
      apoptosis. I-BET151 treatment in two human leukaemia cell lines with different
      MLL fusions alters the expression of a common set of genes whose function may
      account for these phenotypic changes. The mode of action of I-BET151 is, at least
      in part, due to the inhibition of transcription at key genes (BCL2, C-MYC and
      CDK6) through the displacement of BRD3/4, PAFc and SEC components from chromatin.
      In vivo studies indicate that I-BET151 has significant therapeutic value,
      providing survival benefit in two distinct mouse models of murine MLL-AF9 and
      human MLL-AF4 leukaemia. Finally, the efficacy of I-BET151 against human
      leukaemia stem cells is demonstrated, providing further evidence of its potent
      therapeutic potential. These findings establish the displacement of BET proteins
      from chromatin as a promising epigenetic therapy for these aggressive leukaemias.

PMID- 21964342
TI  - Detectable radio flares following gravitational waves from mergers of binary
      neutron stars.
AB  - Mergers of neutron-star/neutron-star binaries are strong sources of gravitational
      waves. They can also launch subrelativistic and mildly relativistic outflows and
      are often assumed to be the sources of short gamma-ray bursts. An electromagnetic
      signature that persisted for weeks to months after the event would strengthen any
      future claim of a detection of gravitational waves. Here we present results of
      calculations showing that the interaction of mildly relativistic outflows with
      the surrounding medium produces radio flares with peak emission at 1.4 gigahertz
      that persist at detectable (submillijansky) levels for weeks, out to a redshift
      of 0.1. Slower subrelativistic outflows produce flares detectable for years at
      150 megahertz, as well as at 1.4 gigahertz, from slightly shorter distances. The
      radio transient RT 19870422 (ref. 11) has the properties predicted by our model,
      and its most probable origin is the merger of a compact neutron-star/neutron-star
      binary. The lack of radio detections usually associated with short gamma-ray
      bursts does not constrain the radio transients that we discuss here (from mildly
      relativistic and subrelativistic outflows) because short gamma-ray burst
      redshifts are typically >0.1 and the appropriate timescales (longer than weeks)
      have not been sampled.

PMID- 21964341
TI  - Corridors of migrating neurons in the human brain and their decline during
      infancy.
AB  - The subventricular zone of many adult non-human mammals generates large numbers
      of new neurons destined for the olfactory bulb. Along the walls of the lateral
      ventricles, immature neuronal progeny migrate in tangentially oriented chains
      that coalesce into a rostral migratory stream (RMS) connecting the subventricular
      zone to the olfactory bulb. The adult human subventricular zone, in contrast,
      contains a hypocellular gap layer separating the ependymal lining from a
      periventricular ribbon of astrocytes. Some of these subventricular zone
      astrocytes can function as neural stem cells in vitro, but their function in vivo
      remains controversial. An initial report found few subventricular zone
      proliferating cells and rare migrating immature neurons in the RMS of adult
      humans. In contrast, a subsequent study indicated robust proliferation and
      migration in the human subventricular zone and RMS. Here we find that the infant
      human subventricular zone and RMS contain an extensive corridor of migrating
      immature neurons before 18 months of age but, contrary to previous reports, this
      germinal activity subsides in older children and is nearly extinct by adulthood.
      Surprisingly, during this limited window of neurogenesis, not all new neurons in
      the human subventricular zone are destined for the olfactory bulb--we describe a
      major migratory pathway that targets the prefrontal cortex in humans. Together,
      these findings reveal robust streams of tangentially migrating immature neurons
      in human early postnatal subventricular zone and cortex. These pathways represent
      potential targets of neurological injuries affecting neonates.

PMID- 21964343
TI  - MG-2477, a new tubulin inhibitor, induces autophagy through inhibition of the
      Akt/mTOR pathway and delayed apoptosis in A549 cells.
AB  - We previously demonstrated that MG-2477 (3-cyclopropylmethyl-7-phenyl-3H
      pyrrolo[3,2-f]quinolin-9(6H)-one) inhibits the growth of several cancer cell
      lines in vitro. Here we show that MG-2477 inhibited tubulin polymerization and
      caused cells to arrest in metaphase. The detailed mechanism of action of MG-2477
      was investigated in a non-small cell lung carcinoma cell line (A549). Treatment
      of A549 cells with MG-2477 caused the cells to arrest in the G2/M phase of the
      cell cycle, with a concomitant accumulation of cyclin B. Moreover, the compound
      induced autophagy, which was followed at later times by apoptotic cell death.
      Autophagy was detected as early as 12h by the conversion of microtubule
      associated protein 1 light chain 3 (LC3-I) to LC3-II, following cleavage and
      lipid addition to LC3-I. After 48h of MG-2477 exposure, phosphatidylserine
      externalization on the cell membrane, caspase-3 activation, and PARP cleavage
      occurred, revealing that apoptotic cell death had begun. Pharmacological
      inhibition of autophagy with 3-methyladenine or bafilomycin A1 increased
      apoptotic cell death, suggesting that the autophagy caused by MG-2477 played a
      protective role and delayed apoptotic cell death. Additional studies revealed
      that MG-2477 inhibited survival signaling by blocking activation of Akt and its
      downstream targets, including mTOR, and FHKR. Treatment with MG-2477 also reduced
      phosphorylation of mTOR downstream targets p70 ribosomal S6 kinase and 4E-BP1.
      Overexpression of Akt by transfection with a Myr-Akt vector decreased MG-2477
      induced autophagy, indicating that Akt is involved. Taken together, these results
      indicated that the autophagy induced by MG-2477 delayed apoptosis by exerting an
      adaptive response following microtubule damage.

PMID- 21964344
TI  - Mechanisms of glutathione disulfide efflux from erythrocytes.
AB  - Glutathione (GSH) plays numerous critical protective roles in the erythrocyte and
      GSH turnover is likely an important factor in regulating susceptibility to
      oxidative stress and toxins. Efflux of glutathione disulfide (GSSG) from
      erythrocytes is an important component in the regulation of GSH levels; however,
      little is known of the mechanisms involved. We hypothesize that multidrug
      resistance associated protein 1 (MRP1) is responsible, in part, for GSSG
      transport from erythrocytes. To test this, we determined the levels of MRP1
      protein in erythrocyte membranes from healthy adults and compared them with
      intracellular levels of GSH. MRP1 levels varied substantially from person to
      person and were inversely correlated with levels of GSH (r = -0.39, P < 0.05). In
      contrast, activity levels of glutamyl cysteine ligase, the rate limiting GSH
      biosynthetic enzyme, were unrelated to GSH levels. To directly determine the role
      of MRP1 in GSSG transport, in vitro studies were conducted examining the effects
      of MRP1 inhibitors MK571 and verapamil on GSSG efflux. Both compounds resulted in
      significant but not complete inhibition (20-53%) of GSSG efflux from cells.
      Overall, these findings support a role for MPR1 in the regulation of erythrocyte
      GSH levels through the transport and elimination of GSSG from cells.

PMID- 21964345
TI  - Subchondral bone as a key target for osteoarthritis treatment.
AB  - Osteoarthritis (OA), the most common form of arthritis, is a debilitating and
      progressive disease that has become a major cause of disability and impaired
      quality of life in the elderly. OA is considered an organ disease that affects
      the whole joint, where the subchondral bone (SB) plays a crucial role. Regardless
      of whether SB alterations precede cartilage damage or appear during the evolution
      of the disease, SB is currently recognised as a key target in OA treatment. In
      fact, bone abnormalities, especially increased bone turnover, have been detected
      in the early evolution of some forms of OA. Systemic osteoporosis (OP) and OA
      share a paradoxical relationship in which both high and low bone mass conditions
      may result in induction and/or OA progression. Recent findings suggest that some
      drugs may be useful in treating both processes simultaneously, at least in a
      subgroup of patients with OA and OP. This review focuses on the role of SB in OA
      pathogenesis, describing relevant underlying mechanisms involved in the process
      and examining the potential activity as disease-modifying anti-osteoarthritic
      drugs (DMOADs) of certain SB-targeting agents currently under study.

PMID- 21964346
TI  - Living with alkaptonuria.

PMID- 21964347
TI  - How does the level of BCG vaccine protection against tuberculosis fall over time?

PMID- 21964348
TI  - Royal Brompton Hospital challenges decision to close its heart surgery unit.

PMID- 21964349
TI  - Doctors are urged to be ambassadors for flu vaccine by getting the jab.

PMID- 21964350
TI  - Dutch GPs are set to strike over 10% cuts to primary care budget.

PMID- 21964351
TI  - Judge rules that woman in minimally aware state should not be allowed to die.

PMID- 21964352
TI  - Excluding older patients from trials is "bad science," conference hears.

PMID- 21964354
TI  - Characterization and prediction of lysine (K)-acetyl-transferase specific
      acetylation sites.
AB  - Lysine acetylation is a well-studied post-translational modification on both
      histone and nonhistone proteins. More than 2000 acetylated proteins and 4000
      lysine acetylation sites have been identified by large scale mass spectrometry or
      traditional experimental methods. Although over 20 lysine (K)-acetyl-transferases
      (KATs) have been characterized, which KAT is responsible for a given protein or
      lysine site acetylation is mostly unknown. In this work, we collected KAT
      specific acetylation sites manually and analyzed sequence features surrounding
      the acetylated lysine of substrates from three main KAT families (CBP/p300,
      GCN5/PCAF, and the MYST family). We found that each of the three KAT families
      acetylates lysines with different sequence features. Based on these differences,
      we developed a computer program, Acetylation Set Enrichment Based method to
      predict which KAT-families are responsible for acetylation of a given protein or
      lysine site. Finally, we evaluated the efficiency of our method, and
      experimentally detected four proteins that were predicted to be acetylated by two
      KAT families when one representative member of the KAT family is over expressed.
      We conclude that our approach, combined with more traditional experimental
      methods, may be useful for identifying KAT families responsible for acetylated
      substrates proteome-wide.

PMID- 21964355
TI  - Micronutrient special issue: coenzyme Q(10) requirements for DNA damage
      prevention.
AB  - Coenzyme Q(10) (CoQ(10)) is an essential component for electron transport in the
      mitochondrial respiratory chain and serves as cofactor in several biological
      processes. The reduced form of CoQ(10) (ubiquinol, Q(10)H(2)) is an effective
      antioxidant in biological membranes. During the last years, particular interest
      has been grown on molecular effects of CoQ(10) supplementation on mechanisms
      related to DNA damage prevention. This review describes recent advances in our
      understanding about the impact of CoQ(10) on genomic stability in cells, animals
      and humans. With regard to several in vitro and in vivo studies, CoQ(10) provides
      protective effects on several markers of oxidative DNA damage and genomic
      stability. In comparison to the number of studies reporting preventive effects of
      CoQ(10) on oxidative stress biomarkers, CoQ(10) intervention studies in humans
      with a direct focus on markers of DNA damage are limited. Thus, more well
      designed studies in healthy and disease populations with long-term follow up
      results are needed to substantiate the reported beneficial effects of CoQ(10) on
      prevention of DNA damage.

PMID- 21964356
TI  - Video analysis of craniofacial soccer incidents: a prospective study.
AB  - OBJECTIVE: The aim of this study was to assess the occurrence of incidents
      involving the craniofacial region during Brazilian Professional Soccer League
      matches. The mechanisms of these incidents and the association between their
      characteristics and severity were also analyzed. DESIGN: Prospective Epidemiology
      Study. METHODS: A total of 113 first division matches of the Brazilian Soccer
      League were analyzed in 2009. Data collected included incident type, site
      affected, causing agent, severity, player position, field zone, referee decision
      and time of the match when the incident took place. Descriptive analysis
      considered absolute and relative frequencies and 95% confidence intervals. Fisher
      Exact Tests were used to test associations (p<=0.05). RESULTS: Out of all
      matches, in 84.1% at least one craniofacial region related incident happened,
      totaling 227 incidents (mean of 2.0 per match). With reference to incident
      mechanisms and characteristics, 91.2% were hits and the most affected site was
      the face (70.0%). The most frequent causing agent was the upper extremity (59.5%)
      and the most frequently affected player was the striker (31.7%). The incident
      severity was associated with player position (p<0.01), the causing agent
      (p<0.01), field zone (p<0.01), site affected (p=0.03) and incident type (p<0.01).
      CONCLUSIONS: Soccer presented a high number of incidents against head and face
      during professional practice in Brazil, representing a real risk to athletes.
      Preventive strategies should be focused on game rule observance and "fair play".

PMID- 21964353
TI  - Life cycle stage-resolved proteomic analysis of the excretome/secretome from
      Strongyloides ratti--identification of stage-specific proteases.
AB  - A wide range of biomolecules, including proteins, are excreted and secreted from
      helminths and contribute to the parasite's successful establishment, survival,
      and reproduction in an adverse habitat. Excretory and secretory proteins (ESP)
      are active at the interface between parasite and host and comprise potential
      targets for intervention. The intestinal nematode Strongyloides spp. exhibits an
      exceptional developmental plasticity in its life cycle characterized by parasitic
      and free-living generations. We investigated ESP from infective larvae, parasitic
      females, and free-living stages of the rat parasite Strongyloides ratti, which is
      genetically very similar to the human pathogen, Strongyloides stercoralis.
      Proteomic analysis of ESP revealed 586 proteins, with the largest number of stage
      specific ESP found in infective larvae (196), followed by parasitic females (79)
      and free-living stages (35). One hundred and forty proteins were identified in
      all studied stages, including anti-oxidative enzymes, heat shock proteins, and
      carbohydrate-binding proteins. The stage-selective ESP of (1) infective larvae
      included an astacin metalloproteinase, the L3 Nie antigen, and a fatty acid
      retinoid-binding protein; (2) parasitic females included a prolyl oligopeptidase
      (prolyl serine carboxypeptidase), small heat shock proteins, and a secreted
      acidic protein; (3) free-living stages included a lysozyme family member, a
      carbohydrate-hydrolyzing enzyme, and saponin-like protein. We verified the
      differential expression of selected genes encoding ESP by qRT-PCR. ELISA analysis
      revealed the recognition of ESP by antibodies of S. ratti-infected rats. A prolyl
      oligopeptidase was identified as abundant parasitic female-specific ESP, and the
      effect of pyrrolidine-based prolyl oligopeptidase inhibitors showed concentration
      and time-dependent inhibitory effects on female motility. The characterization
      of stage-related ESP from Strongyloides will help to further understand the
      interaction of this unique intestinal nematode with its host.

PMID- 21964357
TI  - Cancer stage comparison between dual Medicare-Medicaid eligibles using Medicaid
      as a supplemental health insurance program and low-income nonduals.
AB  - BACKGROUND: Dual-eligibility status for both Medicare and Medicaid is associated
      with unfavorable cancer stage outcomes. However, given the reduced financial
      barriers, duals enrolled in Medicaid prior to cancer diagnosis-or those using
      Medicaid as a supplemental health insurance program (Dual/SHIP)-may have improved
      access to preventive services compared with low-income nonduals (LI/nondual),
      therefore, be more likely to be diagnosed at earlier stages of cancers amenable
      to screening. OBJECTIVES: To compare breast, prostate, and colorectal cancer
      stage at diagnosis between Duals/SHIP and LI/nonduals, adjusting for
      sociodemographic variables, comorbidities, and nursing home status. RESEARCH
      DESIGN: Cross-sectional study using a database developed by linking records from
      the Ohio Cancer Incidence Surveillance System with Medicare and Medicaid files,
      as well as US census data. SUBJECTS: Fee-for-service, Ohio residents aged 65
      years or older, and diagnosed with incident breast, prostate, or colorectal
      cancer in 1997-2001. MEASURES: (1) Unknown stage/unstaged cancer and (2) distant
      stage cancer at diagnosis. RESULTS: Duals/SHIP were more likely than LI/nonduals
      to have unknown stage/unstaged breast cancer (adjusted odds ratio: 1.43, 95%
      Confidence Interval (CI): 1.02-2.0; P = .035). However, this difference was not
      seen in prostate or colorectal cancer. In prostate cancer patients, but not in
      breast or colorectal cancer patients, Dual/SHIP status was associated with
      distant-stage disease (adjusted odds ratio: 1.74, 95% CI: 1.12-2.70; P = .014).
      In colorectal cancer patients, dual status was not associated with cancer stage.
      CONCLUSION: The findings show no benefit associated with Medicaid as SHIP.
      Rather, they indicate that for the most part, cancer stage is comparable between
      Duals/SHIP and LI/nonduals.

PMID- 21964358
TI  - Fire prevention in Delaware: a case study of fire and life safety initiatives.
AB  - CONTEXT: Injuries resulting from residential house fires are a significant public
      health issue. The fire service is engaged in fire prevention activities aimed at
      preventing fire-related morbidity and mortality. The fire service in Delaware is
      regarded by some leaders in the field as a model for fire and life safety
      education (FLSE). OBJECTIVE: We identified 3 questions to guide this research.
      What is the culture and context of fire prevention in Delaware? What prevention
      programs and policies constitute Delaware's fire prevention efforts? What can be
      learned from select model programs regarding their impact, sustainability,
      strengths, limitations, and general applicability? A discussion of the lessons
      learned from Delaware's experience with FLSE initiatives concludes the article.
      DESIGN: We used a single case study design and collected and analyzed data from
      in-depth interviews, documents, and participant observation notes to address the
      research questions. SETTING: Data were collected in Delaware. PARTICIPANTS:
      Interviewees included a purposeful sample of members of the Delaware fire
      service. MAIN OUTCOME MEASURES: Descriptions of the context in which fire
      prevention occurs, the initiatives underway, and the factors associated with
      successfully supporting fire prevention in the state. RESULTS: Data from 16 key
      informant interviews, relevant documents, and direct observations of FLSE events
      revealed a fire service rooted in tradition, dedication, and community. A
      compilation of state and local FLSE initiatives illustrates the diversity of FLSE
      in Delaware. Thematic analysis of the data emphasize the importance of a
      strategic, comprehensive, and coordinated approach to realizing success in
      Delaware's approach to FLSE. CONCLUSIONS: The fire service is an important part
      of the public health infrastructure. While their role as first responders is
      evident, their contributions to prevention are also significant. This research
      suggests ways to support fire service prevention efforts and more fully integrate
      their FLSE work into the public health infrastructure.

PMID- 21964359
TI  - Uncorrected refractive error among first-grade students of different
      racial/ethnic groups in southern California: results a year after school-mandated
      vision screening.
AB  - CONTEXT: The California Department of Education requires that kindergartners
      receive vision screening in preparation for school. Information is not available
      in the literature, however, on the prevalence of and factors associated with
      uncorrected refractive error (ie, the lack of eyeglasses), which is the primary
      cause of decreased visual acuity in children, among first-grade students of
      different racial/ethnic groups in California. OBJECTIVE: To determine the
      proportion of first-grade students with decreased visual acuity who need
      eyeglasses but do not have any and whether the lack of eyeglasses is associated
      with racial/ethnic and other factors. SETTING: Three school districts in Southern
      California. PARTICIPANTS: The University of California, Los Angeles Mobile Eye
      Clinic examined the eyes of 11 332 first-grade students over a 7-year period.
      Statistical analyses included adjusted logistic regression and linear trend
      models. FINDINGS: Among 11 332 first-grade students, 6973 (61.5%) were Latino,
      1511 (13.3%) were Asian/Pacific Islander, 1422 (12.5%) were African American, 310
      (2.7%) were non-Hispanic white, and 1116 (9.8%) were from other or mixed
      races/ethnicities. The prevalence of decreased visual acuity was 8.0%; 95% of
      children with decreased visual acuity (858 of 906 children) lacked eyeglasses
      that would have helped them attain normal vision. The lack of eyeglasses was more
      common in boys and African American/Latino children compared with that in girls
      and non-Hispanic white children, respectively. The percentage of children lacking
      eyeglasses over the years exhibited an increasing linear trend (R = 0.86).
      CONCLUSIONS: Most first-grade students with decreased visual acuity, especially
      African American and Latino children, need eyeglasses but do not have any.
      Interventions to correct decreased visual acuity in first-grade students are
      important because the first grade is a period of critical academic development.

PMID- 21964360
TI  - Setting the standards for collecting ethnicity data in the Commonwealth of
      Massachusetts.
AB  - The 1997 revision to Federal Office of Management and Budget (OMB) Directive No.
      15 Race and Ethnic Standards for Federal Statistics and Administrative Reporting
      provides standard classifications for reporting broad race categories and
      Hispanic/non-Hispanic ethnicity. However, the current system may be masking
      disparities in health behaviors and outcomes across ethnic groups. Since 2000,
      the Massachusetts Department of Public Health has been developing an alternative
      approach to collecting race, ethnicity, and language preference data to better
      serve the local population. Our data collection tool adheres to OMB standards but
      captures detailed ethnicity data independent of broad race categories. We believe
      that training personnel is an essential component of data collection, and we are
      planning to develop online training materials. Although we encourage states to
      learn from our experience, data need to be comparable within and across states as
      well as over time to monitor health disparities.

PMID- 21964361
TI  - Assessing and increasing patient panel size in the public sector.
AB  - CONTEXT: Panel management is a central component of the primary care medical
      home, but faces numerous challenges in the safety net setting. In the San
      Francisco Department of Public Health, many of our community-based primary care
      clinics have difficulty accommodating all patients seeking care. OBJECTIVE: We
      evaluated patient panel size in our 7 clinics providing cradle-to-grave primary
      care services to more than 25,000 active patients. DESIGN: We adjusted panel size
      for age, gender, diagnoses, homelessness, and substance abuse; set related
      policies; and assessed the effects on our clinics. On the basis of our previous
      data and targets set by other safety net providers, we established a minimum of
      1125 patients per full-time paid primary care provider (ie, full-time equivalent
      [FTE]) in April 2009. We calculated the target panel size each clinic would have
      if all their providers reached the minimum panel size goal and compared it with
      the panel size attained by the clinic. RESULTS: Nine months after establishing
      panel size policy, providers reached 82% of the aggregate target panel size. Five
      of the 7 clinics increased their adjusted panel size per FTE in the range of 2%
      to 23%. Two data-oriented and innovative clinics with some of the highest
      adjusted panel sizes per FTE largely maintained their panel size. Two clinics
      that had the lowest adjusted panel size per FTE realized a 23% and 8% respective
      gain; both clinics reduced barriers to new patient appointments. Two clinics
      acquired new providers and experienced a concomitant drop in panel size per FTE
      while the new clinicians expanded their panels. One of these clinics had
      difficulty managing high no-show rates and creating effective appointment
      templates. CONCLUSIONS: Routine data generation, review of data with
      administrators and providers, data-driven policies and panel size standards, and
      interventions to bolster team-based care are important tools for increasing
      capacity at our primary care clinics.

PMID- 21964362
TI  - Needle in a haystack: the yield of syphilis outreach screening at 5 US sites-2000
      to 2007.
AB  - BACKGROUND: Screening for syphilis has been performed for decades, but it is
      unclear if the practice yields many cases at acceptable cost, and if so, at which
      venues. We attempted a retrospective study to determine the costs, yield, and
      feasibility of analyzing health department-funded syphilis outreach screening in
      5 diverse US sites with significant disease burdens. METHODS: Data (venue, costs,
      number of tests, reactive tests, new diagnoses) from 2000 to 2007 were collected
      for screening efforts funded by public health departments from Philadelphia; New
      York City; Washington, District of Columbia; Maricopa County, Arizona (Phoenix);
      and the state of Florida. Crude cost per new case was calculated. RESULTS:
      Screening was conducted in multiple venues including jails, shelters, clubs,
      bars, and mobile vans. Over the study period, approximately 926 258 tests were
      performed and 4671 new syphilis cases were confirmed, of which 225 were primary
      and secondary, and 688 were early latent or high-titer late latent. Jail intake
      screening consistently identified the largest numbers of new cases (including
      67.6% of early and high-titer late-latent cases) at a cost per case ranging from
      $144 to $3454. Data quality from other venues varied greatly between sites and
      was often poor. CONCLUSIONS: Though the yield of jail intake screening was good,
      poor data quality, particularly cost data, precluded accurate cost/yield
      comparisons at other venues. Few cases of infectious syphilis were identified
      through outreach screening at any venue. Health departments should routinely
      collect all cost and testing data for screening efforts so that their yield can
      be evaluated.

PMID- 21964363
TI  - Public health and hospital collaboration:  new opportunities, new reasons to
      collaborate.

PMID- 21964364
TI  - Community benefits and health reform: creating new links for public health and
      not-for-profit hospitals.
AB  - The Patient Protection and Affordable Care Act (PPACA) put new requirements on
      not-for-profit (NFP) hospitals to document provision of community benefits, to
      justify their tax-exempt status. Specific PPACA provisions include requirements
      that NFP hospitals conduct or participate in a community health needs assessment
      and work to address the needs identified. Consideration is given to these
      particular PPACA mandates and to Internal Revenue Service (IRS) actions to
      implement them. The background of concerns that have been expressed about whether
      the NFP hospitals' tax exemption should be continued and a brief history of that
      exemption is noted. Not-for-profit hospitals have resources that the federal
      government is requiring them to bring to public health improvement, during a time
      when the public health agencies at the federal and state level continue to
      experience reductions in funding. Linking of the NFP hospitals' compliance
      activities with the public health agency community health planning activities
      will help fulfill its PPACA requirements and the regulatory reporting
      requirements for the IRS.

PMID- 21964365
TI  - Local health department 2009 H1N1 influenza vaccination clinics-CDC staffing
      model comparison and other best practices.
AB  - Mass vaccination clinic staffing models, such as the Centers for Disease Control
      and Prevention Large-Scale Vaccination Clinic Output and Staff Estimates: An
      Example, provide guidance on appropriate roles and number of staff for successful
      mass vaccination clinics within local and state health departments. The Kent
      County Health Department used this model as a starting point for mass vaccination
      clinics in response to 2009 H1N1 influenza. In addition to discussion of
      successful modification of the Centers for Disease Control and Prevention model
      to maximize local health department mass vaccination clinic efficiency,
      additional best practices including use of the Incident Command System and a
      reservation system are provided. Use of the provided modified staffing model and
      additional best practices will increase the success of health department mass
      vaccination clinics, and should be considered not only for future public health
      emergencies, but also for seasonal influenza vaccination campaigns.

PMID- 21964366
TI  - Local food protection and safety infrastructure and capacity:  a Maryland case
      study.
AB  - INTRODUCTION: In Maryland, county Food Protection Programs (FPP), housed within
      Environmental Public Health (EPH) Divisions, maintain responsibility for regular
      inspection of all food service facilities (FSF). With growing concerns about how
      our food supply is protected, it is important to determine the state and
      effectiveness of our food safety systems. This research elucidates the roles,
      responsibilities, strengths, and weaknesses of Food Safety and Protection
      Programs in Maryland. METHODS: A 16-question survey tool, which addressed facets
      of the local food protection infrastructure, including FSF inspections, staffing,
      budget, and foodborne illness surveillance, was distributed to all 24 county FPP.
      RESULTS: The number of FSF in Maryland increased 97% from 2001 to 2006 and
      counties had an average inspection completion rate of 73%, with a 4% increase
      over the time period. Statewide, there were 4.1 EPH full-time employees (FTE) per
      10 000 population and 1.6 FPP FTE per 10 000 population. EPH Division budgets
      increased 63% statewide, from $19.5 million in 2000 to $31.9 million in 2007. FPP
      budgets also increased 59% over the period, from $6.2 million in 2000 to $9.8
      million in 2007. CONCLUSIONS: This study offers new quantitative measures of the
      demands, capacities, and performance of Food Protection and Safety Programs in
      Maryland. This assessment of local EPH and FPP capacity also offers insight into
      the strengths and weaknesses of the local food protection and safety
      infrastructure. Importantly, it reveals an infrastructure and dedicated food
      protection workforce that inspects the food supply and responds to foodborne
      illness outbreaks. Yet, resources vary substantially from county to county,
      impacting which services can be provided and how well they can be performed. This
      can, in turn, impact the potential risk of foodborne illness and the public's
      overall health.

PMID- 21964367
TI  - Public health efforts to build a surveillance system for child maltreatment
      mortality:  lessons learned for stakeholder engagement.
AB  - CONTEXT: Reducing the number of largely preventable and tragic deaths due to
      child maltreatment (CM) requires an understanding of the magnitude of and risk
      factors for fatal CM and targeted research, policy, and prevention efforts.
      Public health surveillance offers an opportunity to improve our understanding of
      the problem of CM. In 2006, the Centers for Disease Control and Prevention (CDC)
      funded state public health agencies in California, Michigan, and Oregon to
      implement a model approach for routine and sustainable CM surveillance and
      evaluated the experience of those efforts. OBJECTIVE: We describe the experiences
      of 3 state health agencies in building collaborations and partnerships with
      multiple stakeholders for CM surveillance. DESIGN: Qualitative, structured key
      informant interviews were carried out during site visits as part of an evaluation
      of a CDC-funded project to implement a model approach to CM surveillance.
      PARTICIPANTS: Key informants included system stakeholders from state health
      agencies, law enforcement, child protective services, the medical community, and
      child welfare advocacy groups in the 3 funded states. RESULTS: Factors that
      facilitated stakeholder engagement for CM surveillance included the following:
      streamlining and coordinating the work of Child Death Review Teams (CDRTs);
      demonstrating the value of surveillance to non-public health partners; codifying
      relationships with participating agencies; and securing the commitment of
      decision-makers. Legislative mandates were helpful in bringing key stakeholders
      together, but it was not sufficient to ensure sustained engagement. CONCLUSIONS:
      The engagement process yielded multiple benefits for the stakeholders including a
      deeper appreciation of the complexity of defining CM; a greater understanding of
      risk factors for CM; and enhanced guidance for prevention and control efforts.
      States considering or currently undertaking CM surveillance can glean useful
      insights from the experiences of these 3 states and apply them to their own
      efforts to engage stakeholders.

PMID- 21964368
TI  - The status of state boards of health in 2010.
AB  - OBJECTIVE: The objective of the survey was to update information about state
      boards of health throughout the United States and, based on the results of the
      survey, to determine how the National Association of Local Boards of Health can
      serve as a resource to assist state boards in fulfilling their responsibilities
      and duties. DESIGN: A written survey was developed to collect information about
      the composition, organizational structure, statutory authority, roles,
      responsibilities, concerns, and needs of state boards of health. SETTING:
      Information specific to state boards of health has not been collected on a
      routine basis by any organization, therefore the National Association of Local
      Boards of Health sought to compile current information on these boards that will
      be maintained and updated on a routine basis. PARTICIPANTS: Surveys were mailed
      to 31 contacts for state boards of health. MAIN OUTCOME MEASURE: After follow-up
      attempts, responses (n = 27) were received from all but four boards for a
      response rate of 87.1% with one indicating no board. RESULTS: Consumers and
      physicians were most frequently reported as required members of the boards. Board
      members were appointed solely by the governor in 21 (80.8%) states. Nine boards
      (34.6%) indicated an advisory only capacity regarding statutory authority while
      the others were governing, policy making, or had multiple authorities. Specific
      responsibilities of all of the boards included, regardless of statutory
      authority, advising the state chief health officer (84.6%), advising the governor
      (42.3%), and adopting and enforcing statutes (38.5%). CONCLUSIONS: State boards
      of health have undergone changes and likely will continue to evolve in their role
      in public health governance as demonstrated by this survey. This repository of
      current data on state boards of health could be of use to public health
      researchers, boards of health, and national public health organizations in
      strengthening public health governance.

PMID- 21964369
TI  - The impact of missed opportunities on seasonal influenza vaccination coverage for
      healthy young children.
AB  - OBJECTIVE: To estimate the impact of missed opportunities on influenza
      vaccination coverage among 6- through 23-month-old children who sought medical
      care during the 2004-2005 influenza season. DESIGN: Retrospective cohort study.
      SETTING: Fifty-two primary care practice sites located in Rochester, New York,
      Nashville, Tennessee, and Cincinnati, Ohio. PARTICIPANTS: Children 6 through 23
      months of age. METHODS/OUTCOME MEASURE: Charts were reviewed and data collected
      on influenza vaccinations, type of health care visit (well child or other), and
      presence of illness symptoms. Missed opportunity was defined as a practice visit
      by an eligible child during influenza season, when vaccine was available, but
      during which the child did not receive an influenza vaccination. Vaccine was
      assumed to be available between the first and last dates influenza vaccination
      was recorded at that practice. Each child was classified as fully vaccinated,
      partially vaccinated, or unvaccinated. RESULTS: Data were analyzed for 1724
      children, 6 through 23 months of age. Most children (62.0%) had at least 1 missed
      opportunity during this period. Among children with any missed opportunities,
      12.8% were fully and 29.8% were partially vaccinated. Overall, 33.6% of the
      missed opportunities occurred during well child visits and 66.4% during other
      types of visits; 75% occurred when no other vaccines were given. Eliminating all
      missed opportunities would have increased full vaccination coverage from 30.3% to
      49.9%. CONCLUSIONS: Missed opportunities for influenza vaccination are frequent.
      Reducing missed opportunities could significantly increase influenza vaccination
      rates and should be a goal in each practice.

PMID- 21964370
TI  - Using an immunization information system to facilitate a vaccine recall in New
      York City, 2007.
AB  - BACKGROUND: In December 2007, Merck & Co, Inc, initiated a voluntary recall of 10
      lots of PedvaxHIB, and 2 lots of COMVAX when the potential of contamination was
      identified during routine testing of the manufacturing equipment. Merck
      recommended that providers stop vaccinating children using these vaccine lots.
      OBJECTIVE: To describe how the New York City (NYC) Immunization Information
      System was used in the effort to recall vaccines. METHODS: Immediately following
      Merck's announcement, NYC's Bureau of Immunization used the New York Citywide
      Immunization Registry (CIR) to (a) fax and e-mail all pediatric facilities a
      letter informing them of the recall and asking that they immediately remove
      recalled vaccines from their refrigerators; (b) identify facilities that had used
      the recalled lots, on the basis of data reported to the CIR, and contact them
      individually by phone; and (c) monitor the success of the recall by examining the
      number of recalled doses administered and reported to the CIR before and after
      the recall. RESULTS: The alert was faxed and e-mailed to 1928 pediatric
      facilities informing them of the recall. In addition, the Bureau of Immunization
      identified 105 facilities that had reported doses of vaccine from the recalled
      lots to the CIR and called to ask them to check their refrigerators for remaining
      supplies and discontinue use of this vaccine. The number of doses with the
      affected lot numbers reported to the CIR decreased sharply following CIR recall
      notification. Furthermore, the Centers for Disease Control and Prevention and
      Merck reported the return of nearly 50% of publicly and privately purchased
      vaccines from the recalled lots that had been distributed to NYC providers.
      CONCLUSION: Immunization Information Systems can be effective tools for quickly
      identifying providers in possession of recalled vaccine lots, particularly when
      lot numbers are well reported, and for facilitating rapid vaccine recall in
      support of vaccine safety.

PMID- 21964371
TI  - Making the case for accreditation.

PMID- 21964372
TI  - Research, practice, and policy partnerships in pan-Canadian coalitions for cancer
      and chronic disease prevention.
AB  - OBJECTIVE: To describe the development stages of the Coalitions Linking Action
      and Science for Prevention (CLASP) initiative of the Canadian Partnership Against
      Cancer to support research, practice, and policy coalitions focused on cancer and
      chronic disease prevention in Canada. DESIGN: Coalitions Linking Action and
      Science for Prevention was implemented in 3 stages. This article describes Stage
      1 that consisted of an online concept-mapping consultation process, 3 topic
      specific networking and consultation workshops, and 3 context-specific
      networking, coalition development, and planning meetings. These were all
      completed using a participatory engagement approach to encourage knowledge
      exchange across jurisdictions and sectors in Canada. SETTING: Toronto, Ontario;
      Calgary, Alberta; Montreal, Quebec; and Ottawa, Ontario. PARTICIPANTS: More than
      500 researchers, practitioners, and policy specialists were invited to take part
      in the first stage activities. MAIN OUTCOME MEASURES: (1) Participant-identified
      high-priority opportunities for strategic collaboration; (2) Cross-jurisdictional
      and cross-sector representation; and (3) Participant feedback on the CLASP
      processes and activities. RESULTS: Participants from Stage 1 activities were
      distributed across all provinces/territories; 3 jurisdictional levels; and
      research, practice, and policy sectors. Ninety priority opportunities for
      strategic collaboration were identified across all 3 workshops. Participants
      provided detailed feedback about transparency of the RFP (Request for Proposals)
      application process, support needed to level the playing field for potential
      applicants, and valuable suggestions for the adjudication process. CONCLUSIONS:
      Coalitions Linking Action and Science for Prevention engaged hundreds of
      research, practice, and policy experts across Canada focusing social-behavioral,
      clinical, and environmental and occupational opportunities for cancer and chronic
      disease prevention. Given the extent of expert and jurisdictional engagement, the
      substantial Partnership investment in a participatory engagement approach to RFP
      development and potential applicant response suggests that efforts to link cancer
      and chronic disease prevention efforts across jurisdictions and through research,
      practice, and policy collaboration may require this type of a priori investment
      in networking, communication, coordination, and collaboration.

PMID- 21964373
TI  - Cancer Plan Index: a measure for assessing the quality of cancer plans.
AB  - OBJECTIVE: To (1) conduct an in-depth assessment of the content of comprehensive
      cancer control plans and (2) obtain data that can be used to provide guidance to
      grantees supported by the Centers for Disease Control and Prevention's National
      Comprehensive Cancer Control Program (NCCCP) as they refine their plans, and to
      other health professionals as similar planning is done. DESIGN: Through an
      iterative development process, a workgroup of subject matter experts from NCCCP
      and Research Triangle Institute International (RTI International) identified 11
      core or essential components that should be considered in cancer plans on the
      basis of their professional experience and expertise. They also developed a tool,
      the Cancer Plan Index (CPI), to assess the extent to which cancer plans addressed
      the 11 core components. SETTING: Sixty-five comprehensive cancer control programs
      in states, tribes, territories, and jurisdictions funded by the NCCCP. DATA
      SOURCE: Raters reviewed and abstracted all available cancer plans (n = 66), which
      included plans from 62 funded programs and 4 states of the Federated States of
      Micronesia funded by Centers for Disease Control and Prevention as a
      subcontractor of one funded program. Of the 66 plans, 3 plans were used to pilot
      test the CPI and the remaining 63 plans were subsequently reviewed and
      abstracted. MAIN OUTCOME MEASURE(S): The primary outcome measures are national
      level component scores for 11 defined domains (global involvement of
      stakeholders, developing the plan, presentation of data on disease burden, goals,
      objectives, strategies, reduction of cancer disparities, implementation, funds
      for implementation of plan, evaluation, usability of plan), which represent an
      average of the component scores across all available cancer plans. RESULTS: To
      aid in the interpretation and usability of findings, the components were
      segmented into 3 tiers, representing a range high (average score = 2.01-4.00),
      moderate (average score = 1.01-2.00), and low (average score = 0-1.00) levels of
      description of the component. Programs overall provided relatively comprehensive
      descriptions of goals, objectives, and strategies; moderate description of the
      plan development process, presentation of data on disease burden, and plans on
      the reduction of cancer disparities; and little to no description of stakeholder
      involvement plans for implementation, funds for implementation, and evaluation of
      the plan. CONCLUSIONS: Areas of the CPI with low average component scores should
      stimulate technical assistance to the funded programs, either to increase program
      activities or to increase discussion of key activities in the plan.

PMID- 21964374
TI  - A disiloxane-functionalized phosphonium-based ionic liquid as electrolyte for
      lithium-ion batteries.
AB  - A disiloxane-functionalized ionic liquid based on a phosphonium cation and a
      bis(trifluoromethylsulfonyl)imide (TFSI) anion was synthesized and characterized.
      This new ionic liquid electrolyte showed good stability with a lithium transition
      metal oxide cathode and a graphite anode in lithium ion cells.

PMID- 21964375
TI  - Psychological predictors of SMR-BCI performance.
AB  - BACKGROUND: After about 30 years of research on Brain-Computer Interfaces (BCIs)
      there is little knowledge about the phenomenon, that some people - healthy as
      well as individuals with disease - are not able to learn BCI-control. To
      elucidate this "BCI-inefficiency" phenomenon, the current study investigated
      whether psychological parameters, such as attention span, personality or
      motivation, could predict performance in a single session with a BCI controlled
      by modulation of sensorimotor rhythms (SMR) with motor imagery. METHODS: A total
      of N=83 healthy BCI novices took part in the session. Psychological parameters
      were measured with an electronic test-battery including clinical, personality and
      performance tests. Predictors were determined by binary logistic regression
      analyses. RESULTS: The output variable of the Two-Hand Coordination Test (2HAND)
      "overall mean error duration" which is a measure for the accuracy of fine motor
      skills accounted for 11% of the variance in BCI-inefficiency. The Attitudes
      Towards Work (AHA) test variable "performance level" which can be interpreted as
      a degree of concentration and a neurophysiological SMR predictor were also
      identified as significant predictors of SMR BCI performance. CONCLUSION:
      Psychological parameters as measured in this study play a moderate role for one
      session performance in a BCI controlled by modulation of SMR.

PMID- 21964376
TI  - Differential gene expression of RAW 264.7 macrophages in response to the RGD
      peptide lunasin with and without lipopolysaccharide stimulation.
AB  - Lunasin is a novel peptide from soybean with demonstrated chemopreventive
      property. We compared the effect of lunasin on gene expression of RAW 264.7
      macrophages with and without lipopolysaccharide (LPS)-stimulation. Our hypothesis
      was that lunasin will have a differential effect in RAW 264.7 gene expression in
      a normal and challenged state. Analysis of the microarray data using False
      Discovery Rate (FDR) method resulted in the identification of 340 up-regulated
      and 162 down-regulated genes (FDR p-value <0.05) associated with simultaneous
      treatment of lunasin and LPS for 24h. Treatment of lunasin with no LPS for 24h
      resulted in the up-regulation of 855 genes and down-regulation of 397 genes. Pre
      treatment of lunasin for 24h resulted in the up-regulation of 35 genes and down
      regulation of 65 genes in LPS-stimulated RAW 264.7 macrophages. GeneVenn analysis
      of these three sets of genes showed that there are 66 genes common among the
      three groups which are mostly associated with regulation of cell death, ion
      binding and transcription as datamined by DAVID. Analysis of the 838 genes unique
      to lunasin alone by functional annotation clustering tool showed that lunasin
      mostly affected genes associated with RNA processing, apoptosis and protein
      kinase activity. Further datamining of these genes by ingenuity pathway analysis
      (IPA) showed that lunasin affected genes involved in cellular growth and
      proliferation, cellular function and maintenance, and cell to cell signaling and
      interaction. These findings support the potential chemopreventive and
      chemotherapeutic use of lunasin against cancer.

PMID- 21964377
TI  - Corticotropin-releasing factor (CRF) receptor subtypes in mediating neuronal
      activation of brain areas involved in responses to intracerebroventricular CRF
      and stress in rats.
AB  - Corticotropin-releasing factor (CRF) plays an important role in stress responses
      through activation of its receptor subtypes, CRF1 receptor (CRF(1)) and CRF2
      receptor (CRF(2)). The parvocellular paraventricular nucleus of the hypothalamus
      (PVNp), the central nucleus of the amygdala (CeA), and the oval nucleus of the
      bed nucleus of the stria terminalis (BNSTov), which are rich in CRF neurons with
      equivocal expression of CRF(1) and CRF(2), are involved in stress-related
      responses. In these areas, Fos expression is induced by various stimuli, although
      the functions of CRF receptor subtypes in stimuli-induced Fos expression are
      unknown. To elucidate this issue and to examine whether Fos is expressed in CRF
      or non-CRF neurons in these areas, the effects of antalarmin and antisauvagine-30
      (AS-30), CRF(1)- and CRF(2)-specific antagonists, respectively, on
      intracerebroventricular (ICV) CRF- or 60min-restraint-induced Fos expression were
      examined in rats. ICV CRF increased the number of Fos-positive CRF and non-CRF
      neurons in the PVNp, with the increases being inhibited by antalarmin in CRF and
      non-CRF neurons and by AS-30 in CRF neurons. Restraint also increased Fos
      positive CRF and non-CRF neurons in the PVNp, with the increases being inhibited
      by antalarmin in the CRF neurons. ICV CRF also increased Fos-positive non-CRF
      neurons in the CeA and the BNSTov, which was inhibited by AS-30 in both areas,
      and inhibited by antalarmin in the BNSTov only. Restraint increased Fos-positive
      non-CRF neurons in the CeA and BNSTov, with the increases being almost completely
      inhibited by either antagonist. These results indicate that both ICV CRF and
      restraint activate both CRF and non-CRF neurons in the PVNp and non-CRF neurons
      in the CeA and BNSTov, and that the activation is mediated by CRF(1) and/or
      CRF(2). However, the manner of involvement for CRF(1) and CRF(2) in ICV CRF- and
      restraint-induced activation of neurons differs with respect to the stimuli and
      brain areas; being roughly equivalent in the CeA and BNSTov, but different in the
      PVNp. Furthermore, the non-CRF(1&2)-mediated signals seem to primarily play a
      role in restraint-induced activation of non-CRF neurons in the PVNp since the
      activation was not inhibited by CRF receptor antagonists.

PMID- 21964378
TI  - Constitutive SIRT1 overexpression impairs mitochondria and reduces cardiac
      function in mice.
AB  - Heart failure is associated with a change in cardiac energy metabolism. SIRT1 is
      a NAD(+)-dependent protein deacetylase, and important in the regulation of
      cellular energy metabolism. To examine the role of SIRT1 in cardiac energy
      metabolism, we created transgenic mice overexpressing SIRT1 in a cardiac-specific
      manner, and investigated cardiac functional reserve, energy reserve, substrate
      uptake, and markers of mitochondrial function. High overexpression of SIRT1
      caused dilated cardiomyopathy. Moderate overexpression of SIRT1 impaired cardiac
      diastolic function, but did not cause heart failure. Fatty acid uptake was
      decreased and the number of degenerated mitochondria was increased dependent on
      SIRT1 gene dosage. Markers of reactive oxygen species were decreased. Changes in
      morphology and reactive oxygen species were associated with the reduced
      expression of genes related to mitochondrial function and autophagy. In addition,
      the respiration of isolated mitochondria was decreased. Cardiac function was
      normal in transgenic mice expressing a low level of SIRT1 at baseline, but the
      mice developed cardiac dysfunction upon pressure overload. In summary, the
      constitutive overexpression of SIRT1 reduced cardiac function associated with
      impaired mitochondria in mice.

PMID- 21964379
TI  - Magnesium-deficiency does not alter calcineurin inhibitors activity in mice.
AB  - INTRODUCTION: Tacrolimus (TAC) and cyclosporin (CsA) are commonly responsible for
      hypomagnesemia that predisposes in turn for hypertension, renal impairment and
      encephalopathy. OBJECTIVE: The effects of TAC on Mg(2+)-homeostasis and of pre
      existing Mg(2+)-deficiency on TAC immunosuppressive activity were compared to CsA
      in mice. METHODS: Mg(2+) was quantified in plasma, erythrocytes, urine, feces,
      and femurs from mice treated with TAC 5mg/kg/day. Immunosuppression was assessed
      in splenocytes by mixed lymphocyte reaction, IL-2 quantification and CN activity
      determination. RESULTS: Plasma and urine Mg(2+) levels in TAC-treated mice were
      significantly lower from day 7 until day 21 (p<0.05 versus control) and returned
      to control value at day 28. Mg(2+) levels were unchanged in erythrocyte, feces
      and femur. Inhibition of allogeneic proliferation, IL-2 production and CN
      activity were 68, 56 and 30% lower (p<0.01) after 7 days of TAC-treatment, and
      72, 68 and 51% lower (p<0.01) after 7 days of CsA-treatment with a dose of
      50mg/kg/day. Dietary-induced hypomagnesemia resulted in significant inhibition of
      CN activity (p<0.01) without alteration of IL-2 production or allogeneic
      proliferation. However, it did not alter the effects observed with CsA- or TAC
      treatment on allogeneic proliferation, IL-2 production and CN activity.
      CONCLUSION: By contrast with CsA, long-course TAC-treatment induced an early, but
      transient, and moderate hypomagnesemia without alteration of bone or erythrocyte
      stocks, intestinal absorption or renal function. Therefore, in clinical use, TAC
      should be preferred to CsA in patients with pathological or pharmacological
      conditions which favor Mg(2+)-deficiency. However, dietary-induced hypomagnesemia
      did not alter the immunosuppressive effects of TAC and CsA.

PMID- 21964380
TI  - Protective effects of quercetin against hydrogen peroxide-induced apoptosis in
      human neuronal SH-SY5Y cells.
AB  - Hydrogen peroxide (H(2)O(2)) is a major reactive oxygen species that has been
      implicated in various neurodegenerative diseases. Quercetin, one of the plant
      flavonoids, has been reported to harbor various physiological properties
      including antioxidant activity. In this study, we investigated the
      neuroprotective effects of quercetin against H(2)O(2)-induced apoptosis in human
      neuronal SH-SY5Y cells. H(2)O(2)-mediated cytotoxicity and lactate dehydrogenase
      release were suppressed in a quercetin concentration-dependent manner. In
      addition, quercetin repressed the expression of the pro-apoptotic Bax gene and
      enhanced that of the anti-apoptotic Bcl-2 gene in SH-SY5Y cells. Moreover,
      quercetin effectively inhibited the activation of the caspase cascade that leads
      to DNA fragmentation, a key feature of apoptosis, and subsequent cell death.
      These results indicate the importance of quercetin in protecting against H(2)O(2)
      mediated neuronal cell death. Thus, quercetin might potentially serve as an agent
      for prevention of neurodegenerative diseases caused by oxidative stress and
      apoptosis.

PMID- 21964381
TI  - Comparison of focally induced epileptiform activities in C57BL/6 and BALB/c mice
      by using in vivo EEG recording.
AB  - Epilepsy characterized by repeated seizures is influenced by genetic factors.
      Seizure response of inbred mouse strains changes depending on the variety of
      stimuli including chemical (e.g., pentylenetetrazole, nicotine, cocaine, NMDA,
      kainate), physical (e.g., auditory) or electrical. In this study, we compared the
      susceptibilities of C57BL/6 and BALB/c mice strains to penicillin induced
      epileptiform activity (a focally induced, experimental epilepsy model), by
      analyzing the spike onset latency, spike amplitude and spike frequency. The power
      spectrums of baseline EEGs were also investigated. We found no alterations of
      spike onset latencies between the C57 and BALB mice. However, spike amplitudes
      and spike frequencies were found to be higher in BALB mice than C57 mice. With
      regard to EEG power spectrum, absolute power of investigated bands was not
      different between the two strains. Interestingly, the relative power of all
      investigated bands differed significantly between two strains. The relative power
      of delta and theta was lower whereas relative power of alpha, beta and gamma was
      higher in C57 mice compared to BALB mice. In conclusion, our findings showed that
      BALB mice are more sensitive to penicillin induced epileptiform activity when
      compared to C57 strain.

PMID- 21964382
TI  - Transient tactile allodynia following intrathecal puncture in mouse:
      contributions of Toll-like receptor signaling.
AB  - Studies of spinal drug action in mice often involve percutaneous intrathecal drug
      administration delivered in a lightly anesthetized animal. A successful lumbar
      intrathecal (IT) needle stick of a lightly anesthetized (isoflurane) mouse evokes
      a tail flick, which is an indication of local spinal nerve stimulation.
      Immediately upon arousal, a hind paw tactile allodynia, as measured with von Frey
      hairs (pre 1.55+/-0.11 g vs. injected 0.66+/-0.08 g) lasts 3-4 h. In a similarly
      anesthetized mouse without the needle stick, a 1-h allodynia was noted. In
      studies on spinal Toll-like receptor (TLR) signaling, we observed that following
      intrathecal puncture and mechanical stimulation of the nerve roots mice deficient
      in TLR down-stream signaling (Myd88(-/-)/Trif(lps2)), displayed only the
      transient (1-h) allodynia otherwise observed following isoflurane alone. These
      data suggest that the extended period of hyperalgesia observed with needle
      penetration of the dura and mechanical stimulation of the nerve roots requires
      signaling through the MyD88/TRIF pathways and supports the intrinsic role of Toll
      like receptors in the allodynia secondary to the minor nerve activation occurring
      during the intradural puncture.

PMID- 21964383
TI  - Role of 5-HT(1A) and 5-HT(1B) receptors in the antidepressant-like effect of
      piperine in the forced swim test.
AB  - Our previous studies have showed that treating mice with piperine significantly
      decreased the immobility time of the animals in the forced swim test and tail
      suspension test, which was related to up-regulation of serotonin (5-HT) level in
      the brain. The purpose of this study is to explore the contribution of 5-HT
      receptors in the antidepressant-like effect of piperine. The results showed that
      pre-treating mice with methiothepin (a non-selective 5-HT receptor antagonist,
      0.1mg/kg, intraperitoneally), 4-(2'-methoxy-phenyl)-1-[2'-(n-2"-pyridinyl)-p
      iodobenzamino-]ethyl-piperazine (a selective 5-HT(1A) receptor antagonist,
      1mg/kg, subcutaneously) or 1-(2-(1-pyrrolyl)-phenoxy)-3-isopropylamino-2-propanol
      (a 5-HT(1B) receptor antagonist, 2.5mg/kg, intraperitoneally) was found to
      abolish the anti-immobility effect of piperine (10mg/kg, intraperitoneally) in
      the forced swim test. On the other hand, a sub-effective dose of piperine
      (1mg/kg, intraperitoneally) produced a synergistic antidepressant-like effect
      with (+)-8-hydroxy-2-(di-n-propylamino)tetralin (a 5-HT(1A) receptor agonist,
      1mg/kg, intraperitoneally) or anpirtoline (a 5-HT(1B) receptor agonist,
      0.25mg/kg, intraperitoneally). Taken together, these results suggest that the
      antidepressant-like effect of piperine in the mouse forced swim test may be
      mediated, at least in part, by the activation of 5-HT(1A) and 5-HT(1B) receptors.

PMID- 21964384
TI  - Clavulanic acid increases dopamine release in neuronal cells through a mechanism
      involving enhanced vesicle trafficking.
AB  - Clavulanic acid is a CNS-modulating compound with exceptional blood-brain barrier
      permeability and safety profile. Clavulanic acid has been proposed to have anti
      depressant activity and is currently entering Phase IIb clinical trials for the
      treatment of Major Depressive Disorder (MDD). Studies have also shown that
      clavulanic acid suppresses anxiety and enhances sexual functions in rodent and
      primate models by a mechanism involving central nervous system (CNS) modulation,
      although its detailed mechanism of action has yet to be elucidated. To further
      examine its potential as a CNS modulating agent as well as its mechanism of
      action, we investigated the effects of clavulanic acid in neuronal cells. Our
      results indicate that clavulanic acid enhances dopamine release in PC12 and SH
      SY5Y cells without affecting dopamine synthesis. Furthermore, using affinity
      chromatography we were able to identify two proteins, Munc18-1 and Rab4 that
      potentially bind to clavulanic acid and play a critical role in neurosecretion
      and the vesicle trafficking process. Consistent with this result, an increase in
      the translocation of Munc18-1 and Rab4 from the cytoplasm to the plasma membrane
      was observed in clavulanic acid treated cells. Overall, these data suggest that
      clavulanic acid enhances dopamine release in a mechanism involving Munc18-1 and
      Rab4 modulation and warrants further investigation of its therapeutic use in CNS
      disorders, such as depression.

PMID- 21964385
TI  - Association between wind-up ratio and central serotonergic function in healthy
      subjects and depressed patients.
AB  - Temporal summation of C-fiber evoked responses generates an increase in action
      potential discharge in second-order neurons and in perceived pain intensity (wind
      up). This may be related to the central serotonergic system which modulates and
      partly inhibits sensory input. Aim of the study was to investigate the
      relationship between wind-up and serotonergic activity using loudness dependence
      of auditory evoked potentials (LDAEP). 18 healthy subjects were compared to 18
      patients with major depression, a disease with a putative serotonin deficit. They
      were examined with quantitative sensory testing (QST) using the protocol of the
      German Research Network on Neuropathic Pain (DFNS), including the wind-up ratio
      (WUR), LDAEP, and psychometric measurements. We found a slight positive
      correlation between WUR and LDAEP both in healthy controls and depressed patients
      combined (r=0.340, p=0.043), indicating that WUR may be modulated by serotonergic
      activity. It can be concluded that inhibitory control to noxious stimuli is
      partly associated with the central serotonergic function as indicated by LDAEP.

PMID- 21964386
TI  - Central 5-HT3 receptor-induced hypothermia is associated with reduced metabolic
      rate and increased heat loss.
AB  - Activation of central 5-HT(3) receptors by the selective agonist m-CPBG (1-(3
      chlorophenyl)biguanide hydrochloride, 40 nM i.c.v.) produced stronger hypothermic
      effect in mice than activation of 5-HT(1A) receptors by their agonist 8-OH-DPAT
      (8-hydroxy-2-(di-n-propilamino)tetralin) injected by the same route at an
      equimolar dose. The hypothermic effect of m-CPBG was realized by influence on
      both the heat production and the heat loss: oxygen consumption and CO(2)
      expiration were decreased; heat dissipation determined by the tail skin
      temperature was increased. The heat loss effect of 5-HT(3) receptors was
      significantly shorter than the decrease in metabolism indicating the prevalent
      role of heat production decrease in 5-HT(3) receptor-induced deep and long-lasing
      hypothermia. In addition, the decrease in the respiratory exchange ratio (RER)
      was shown suggesting that the activation of the 5-HT(3) receptors switched
      metabolism to prevalent use of lipids as the main energetic substrate. 5-HT(1A)
      receptor agonist 8-OH-DPAT (40 nM i.c.v.) produced less depressing effect on
      general metabolism: a decrease in oxygen consumption and CO(2) excretion began
      later and was not so deep as after m-CPBG administration. Heat-loss effect of 5
      HT(1A) receptors activation was not observed. In contrast to m-CPBG effect, RER
      after 5-HT(1A) receptors activation raised immediately after injection and then
      gradually decreased to the values observed in m-CPBG-treated mice. Obtained
      results show that activation of central 5-HT(3) receptors are more effective in
      hypothermia induction due to marked decrease in thermogenesis and increase in
      heat loss.

PMID- 21964387
TI  - Age- and duration-dependent effects of MPTP on cortical serotonin systems.
AB  - It has been well established that aging is the most prominent risk factor for PD.
      In the MPTP mouse model which has been widely used to study PD, studies have
      shown that MPTP exhibits its neurotoxic effects on the dopaminergic system in an
      age-dependent manner. Although it is recognized the serotonergic system is
      impacted in PD, how aging influences serotonergic neurodegeneration in PD has not
      been adequately investigated. In the present studies, we examined the long-term
      effects of MPTP treatment on regional concentrations of dopamine (DA), serotonin
      (5-HT) and norepinephrine (NE) in the striatum and prefrontal cortex (PFC). We
      also determined if there are differences in the age-dependent vulnerability of
      the monoaminergic system to MPTP. In young (3-month-old) mice, MPTP produced
      significant decreases in striatal DA but no changes in striatal 5-HT and NE three
      weeks after MPTP treatment. There was partial recovery of striatal DA
      concentrations 18 months later. This was accompanied by elevated striatal 5-HT.
      In the PFC, NE was decreased but there was complete recovery 18 months later. By
      contrast, we observed a long-term decrease in prefrontal 5-HT with no recovery of
      5-HT concentrations 18 months after MPTP treatment. Striatal DA and NE but not 5
      HT neurons exhibited age-dependent vulnerability to MPTP. Aging had no influence
      on the neurotoxic effects of MPTP in the PFC. Thus, there is divergence in the
      response of DA and 5-HT systems to MPTP neurotoxicity.

PMID- 21964388
TI  - Effects of unilateral nigrostriatal dopamine depletion on peripheral glucose
      tolerance and insulin signaling in middle aged rats.
AB  - Clinical studies indicate an increased incidence of impaired glucose tolerance in
      individuals with Parkinson's disease (PD). The mechanisms that underlie this co
      morbidity are currently unknown. The purpose of this study was to analyze
      peripheral glucose tolerance following severe unilateral nigrostriatal dopamine
      (DA) depletion, and to determine whether central and peripheral insulin signaling
      was affected in the 6-hydroxydopamine (6-OHDA) middle-aged rat model of PD.
      Although serum insulin levels differed significantly between the 6-OHDA and sham
      groups over the course of a glucose tolerance test six weeks post-lesion, no
      significant effect on glucose tolerance or insulin signaling in skeletal muscle
      was observed. In contrast, markers of striatal insulin resistance were evident in
      the rats. These data suggest that while 6-OHDA may affect serum insulin levels
      and striatal insulin signaling, the unilateral 6-OHDA lesion model does not
      induce glucose intolerance or peripheral insulin resistance, at least at the six
      week post-lesion timepoint.

PMID- 21964389
TI  - Spatial orientation deficit in children due to cerebellum astrocytoma pediatric
      tumor obtained by means of the Attentional Network Test.
AB  - Cerebellum astrocytomas are the most typical nervous system tumors in children.
      Several cognitive deficits have been previously described. These deficits are
      probably produced by cerebellar connection and gray matter damage. The present
      study examines attentional deficits in children operated on for cerebellum
      astrocytomas, using an attentional paradigm with theoretical and clinical bases:
      the Attentional Network Test (ANT). This test was designed considering the
      attentional network theory proposed by Posner, and its usefulness has been
      demonstrated in clinical settings. Children operated on for cerebellar
      astrocytoma showed a mild attentional deficit in the orientation network.

PMID- 21964390
TI  - Association between suicide attempt and a tri-allelic functional polymorphism in
      serotonin transporter gene promoter in Chinese patients with schizophrenia.
AB  - Mounting evidence supports the association between a polymorphism in the
      serotonin transporter gene promoter region (5-HTTLPR) and suicidal behaviour.
      Recently, a novel variant of the 5-HTTLPR L allele was identified. The previously
      unknown L(G) allele produced similar levels of gene expression to the S allele
      and might have been misclassified as a "high-expression" allele in previous
      association studies. In this study, we aimed to compare the genotype distribution
      of the tri-allelic 5-HTTLPR polymorphism in 168 Chinese patients with
      schizophrenia, including 60 suicide attempters and 108 non-suicide attempters. In
      our analysis, which used the L(A) dominant model, it was found that the L(A)
      allele carriers were significantly more likely to have attempted suicide
      (p=0.035). Further analysis showed this association existed only in male patients
      (p=0.012). A similar association between the L(A) allele and violent suicide
      attempt was also found (p=0.028). In addition, logistic regression confirmed our
      findings that male L(A) allele carriers were at a higher risk of suicide,
      although the lack of a significant association in females may reflect
      insufficient power due to small sample size. However, no association was found
      when we examined the traditional bi-allelic 5-HTTLPR. These findings differ from
      those reported in Caucasian subjects, where no associations have been reported.
      Different genetic backgrounds may give rise to different allelic distribution,
      causing differential effects on the expression of endophenotypes of suicide
      behaviours. Although the potential influence of multiple comparisons might weaken
      our findings, our study provides preliminary evidence for a potentially gender
      specific role of a "high-expression" 5-HTTLPR polymorphism in susceptibility to
      suicide in Chinese patients with schizophrenia.

PMID- 21964391
TI  - Exon 4-skipping GLT-1: a new form of an abundantly expressed glutamate
      transporter.
AB  - GLT-1 (EAAT2) is an abundant glial glutamate transporter in the mammalian brain.
      It plays important roles, especially in the termination of neurotransmitter
      signals at excitatory synapses in grey matter. In normal brain, alternative
      splicing of GLT-1 has been described, where exons in the GLT-1 gene are skipped
      or intronic sequences spliced in to generate new sequences. This study describes
      the isolation of a cDNA clone encoding a new splice variant of GLT-1 where exon 4
      is skipped. This novel variant was isolated by RT-PCR cloning from adult rat
      brain and encodes a protein of 500 amino acids (MW ~54.5 kDa). RT-PCR analysis
      showed that mRNA was readily detectable in various brain regions of rat, primary
      astrocyte cultures and in tissues such as testis, but little mRNA was detectable
      in retina and liver. An antibody that selectively recognizes exon-4 skipping GLT
      1 revealed strong signals in Western blots and labelled grey matter astrocytes.
      We conclude that exon-4 skipping GLT 1 is abundantly expressed in the brain and
      may represent either a functional glutamate transporter or a modulator of
      glutamate transporter function.

PMID- 21964392
TI  - Neuronal nicotinic receptor antagonist reduces anxiety-like behavior in mice.
AB  - Brain cholinergic neurotransmission has been implicated in the modulation of
      anxiety in humans and evidence suggests that drugs targeting neuronal nicotinic
      acetylcholine receptor (nAChR) could have potential for the treatment of anxiety.
      The objective of present study was to examine anxiolytic effects of lobeline
      (0.04 or 0.1 mg/kg), a nAChR antagonist, in C57BL/6J mice using elevated plus
      maze (EPM) and marble-burying test. Lobeline (0.04 mg/kg) significantly increased
      open arm time on EPM and reduced number of marbles buried. Similarly,
      mecamylamine (0.3 mg/kg) produced anxiolytic effects, while peripherally acting
      hexamethonium (0.3 mg/kg) failed to produce any response. These results provide
      evidence that lobeline has anxiolytic potential and nAChR antagonists may
      represent a new class of anxiolytics in humans.

PMID- 21964393
TI  - Are diurnal changes in foot sole sensation dependent on gait activity?
AB  - The foot sole is loaded during stance and gait and plantar cutaneous
      mechanoreceptors sense the local stress distribution. It is not clear whether the
      perception thresholds of these mechanoreceptors change during the day and how
      they respond to walking activities. The primary aim of the present study was to
      investigate diurnal changes of plantar sensitivity. Furthermore, the aim was to
      find out whether daily changes depend on the individual level of step activity.
      Twenty-six healthy subjects, 17 women and 9 men, aged 28.6+/-6.7 years
      participated in the study. Detection thresholds to light touch were measured in
      six plantar regions with Semmes-Weinstein monofilaments in the morning, noon and
      afternoon. Step activity was recorded with a StepWatchTM Activity Monitor and
      analyzed for three periods (8 a.m.-4 p.m., 8 a.m.-12 p.m., 12 p.m.-4 p.m.). The
      hallux, the 3rd metatarsal head and the heel showed significantly decreased
      detection thresholds from 8 a.m. to 4 p.m. (p<=0.05). A fair correlation between
      the decrease of detection threshold and the total number of steps was found for
      the 3rd metatarsal head and the heel (p<=0.05). Foot sole sensation appears to
      improve during the day and seems to be associated with the step activity. This
      may reflect an improving transfer of afferent information to the central nervous
      system during the day as well as an adaptation of receptors to gait activity.

PMID- 21964394
TI  - Structure determination of membrane proteins in five easy pieces.
AB  - Rotational Alignment (RA) solid-state NMR provides the basis for a general method
      for determining the structures of membrane proteins in phospholipid bilayers
      under physiological conditions. Membrane proteins are high priority targets for
      structure determination, and are challenging for existing experimental methods.
      Because membrane proteins reside in liquid crystalline phospholipid bilayer
      membranes it is important to study them in this type of environment. The RA solid
      state NMR approach we have developed can be summarized in five steps, and
      incorporates methods of molecular biology, biochemistry, sample preparation, the
      implementation of NMR experiments, and structure calculations. It relies on solid
      state NMR spectroscopy to obtain high-resolution spectra and residue-specific
      structural restraints for membrane proteins that undergo rotational diffusion
      around the membrane normal, but whose mobility is otherwise restricted by
      interactions with the membrane phospholipids. High resolution spectra of membrane
      proteins alone and in complex with other proteins and ligands set the stage for
      structure determination and functional studies of these proteins in their native,
      functional environment.

PMID- 21964397
TI  - Selective internal radiation therapy (SIRT) in primary or secondary liver cancer.
AB  - Most patients with a history of common solid tumors will in the end develop liver
      metastases. Next to that, primary liver cancer, is a frequent cancer with fatal
      liver failure in the majority of patients. Selective internal radiation therapy
      (SIRT), has gradually been introduced over the recent years and is a promising,
      innovative albeit palliative treatment modality. The specific clinical background
      with regard to the indication and methodology of SIRT is presented and discussed
      in this paper.

PMID- 21964395
TI  - A helical processing pipeline for EM structure determination of membrane
      proteins.
AB  - Electron crystallography plays a key role in the structural biology of integral
      membrane proteins (IMPs) by offering one of the most direct means of providing
      insight into the functional state of these molecular machines in their lipid
      associated forms, and also has the potential to facilitate examination of
      physiologically relevant transitional states and complexes. Helical or tubular
      crystals, which are the natural product of proteins crystallizing on the surface
      of a cylindrical vesicle, offer some unique advantages, such as three-dimensional
      (3D) information from a single view, compared to other crystalline forms. While a
      number of software packages are available for processing images of helical
      crystals to produce 3D electron density maps, widespread exploitation of helical
      image reconstruction is limited by a lack of standardized approaches and the
      initial effort and specialized expertise required. Our goal is to develop an
      integrated pipeline to enable structure determination by transmission electron
      microscopy (TEM) of IMPs in the form of tubular crystals. We describe here the
      integration of standard Fourier-Bessel helical analysis techniques into Appion,
      an integrated, database-driven pipeline.

PMID- 21964396
TI  - Combination of isothermal titration calorimetry and time-resolved luminescence
      for high affinity antibody-ligand interaction thermodynamics and kinetics.
AB  - For experiments using synthetic ligands as probes for biological experiments, it
      is useful to determine the specificity and affinity of the ligands for their
      receptors. As ligands with higher affinities are developed (K(A)>10(8)M(-1);
      K(D)<10(-8)M), a new challenge arises: to measure these values accurately.
      Isothermal titration calorimetry measures heat produced or consumed during ligand
      binding, and also provides the equilibrium binding constant. However, as normally
      practiced, its range is limited. Displacement titration, where a competing weaker
      ligand is used to lower the apparent affinity of the stronger ligand, can be used
      to determine the binding affinity as well as the complete thermodynamic data for
      ligand-antibody complexes with very high affinity. These equilibrium data have
      been combined with kinetic measurements to yield the rate constants as well. We
      describe this methodology, using as an example antibody 2D12.5, which captures
      yttrium S-2-(4-aminobenzyl)-1, 4, 7, 10-tetraazacyclododecanetetraacetate.

PMID- 21964398
TI  - Peripheral blood gene expression in postinfective fatigue syndrome following from
      three different triggering infections.
AB  - BACKGROUND: Several infections trigger postinfective fatigue syndromes, which
      share key illness characteristics with each other and with chronic fatigue
      syndrome (CFS). Previous cross-sectional case-control studies of CFS have
      suggested that unique gene expression signatures are evident in peripheral blood
      samples. METHODS: Peripheral blood transcriptomes in samples collected
      longitudinally, in 18 subjects with a fatigue syndrome lasting >= 6 months after
      acute infection due to Epstein-Barr virus, Ross River virus, or Coxiella burnetii
      (Q fever), and 18 matched control subjects who had recovered promptly, were
      studied by microarray (n = 127) and confirmatory quantitative polymerase chain
      reaction (PCR). Gene expression patterns associated with CFS were sought by
      univariate statistics and regression modeling. RESULTS: There were 23 genes with
      modest differential expression (0.6-2.3-fold change) in within-subject
      comparisons of early, symptomatic time points with late, recovered time points.
      There were modest differences found in 63 genes, either in cross-sectional
      comparison of cases and controls at 6 months after infection onset or in the
      regression model. There were 223 genes significantly correlated with individual
      symptom domains. Quantitative PCR confirmed 33 (73%) of 45 genes-none were
      consistent across cohorts. CONCLUSIONS: Although the illness characteristics of
      patients with postinfective fatigue syndromes have more similarities than
      differences, no reliable peripheral blood gene expression correlate is evident.

PMID- 21964399
TI  - Combined oral contraceptive use increases HPV persistence but not new HPV
      detection in a cohort of women from Thailand.
AB  - BACKGROUND: Women diagnosed with cervical cancer report longer duration and more
      recent use of combined oral contraceptives (COCs). It is unclear how COC use
      impacts risk of cervical carcinogenesis. METHODS: We estimated the risk of new
      human papillomavirus (HPV) DNA detection and persistence among 1135 human
      immunodeficiency virus (HIV)-negative women aged 20-37 years from Thailand who
      were followed for 18 months at 6-month intervals. Type-specific HPV DNA,
      demographic information, hormonal contraceptive use, sexual behavior, genital
      tract coinfection, and Papanicolaou test results were assessed at baseline and
      each follow-up. RESULTS: Women who reported current COC use during follow-up were
      less likely to clear HPV infection compared with nonusers, independent of sexual
      behavior, and Papanicolaou test diagnosis (AHR: 0.67 [95% CI: .49-.93]). Similar
      associations were not observed among women reporting current use of
      depomedroxyprogesterone acetate (DMPA). Neither COC nor DMPA use was
      significantly associated with new HPV DNA detection. CONCLUSIONS: These data do
      not support the hypothesis that contraceptive use is associated with cervical
      cancer risk via increased risk of HPV acquisition. The increased risk of HPV
      persistence observed among current COC users suggests a possible influence of
      female sex hormones on host response to HPV infection.

PMID- 21964400
TI  - Six-month incidence, persistence, and factors associated with persistence of anal
      human papillomavirus in men: the HPV in men study.
AB  - BACKGROUND: Although there are limited numbers of incidence and persistence
      estimates for anal human papillomavirus (HPV) in women and in men who have sex
      with men (MSM), there are no such reports for men who have sex with women (MSW).
      METHODS: Genotyping was performed on anal samples from men, aged 18-70, from Sao
      Paulo, Brazil; Cuernavaca, Mexico; and Tampa, Florida, who provided specimens at
      enrollment and the 6-month visit of a 4-year prospective study. Eligibility
      included no history of genital warts or human immunodeficiency virus. A total of
      954 MSW and 156 MSM provided evaluable specimens at both visits. Persistence was
      defined as type-specific infection at each visit. RESULTS: Incident anal
      infection was common among both MSM and MSW but generally higher for MSM for HPV
      groups and specific genotypes. A total of 5.1% of MSM and 0.0% of MSW had a
      persistent HPV-16 infection at the 6-month visit. Cigarette smoking among MSM and
      age among MSW were associated with persistent infection with any HPV genotype.
      CONCLUSIONS: Although anal HPV infection is commonly acquired by both MSW and
      MSM, incident events and persistence occurred more often among MSM. Cigarette
      smoking is a modifiable risk factor that may contribute to HPV persistence among
      MSM.

PMID- 21964401
TI  - Fetal origins of neonatal lung disease: understanding the pathogenesis of
      bronchopulmonary dysplasia.

PMID- 21964403
TI  - The dopamine D(2) receptor is expressed and sensitizes adenylyl cyclase activity
      in airway smooth muscle.
AB  - Dopamine receptors are G protein-coupled receptors that are divided into two
      subgroups, "D(1)-like" receptors (D(1) and D(5)) that couple to the G(s) protein
      and "D(2)-like" receptors (D(2), D(3), and D(4)) that couple to G(i). Although
      inhaled dopamine has been reported to induce bronchodilation in patients with
      asthma, functional expression of dopamine receptor subtypes has never been
      described on airway smooth muscle (ASM) cells. Acute activation of G(i)-coupled
      receptors inhibits adenylyl cyclase activity and cAMP synthesis, which
      classically impairs ASM relaxation. In contrast, chronic activation of G(i)
      coupled receptors produces a paradoxical enhancement of adenylyl cyclase activity
      referred to as heterologous sensitization. We questioned whether the dopamine
      D(2)-like receptor is expressed on ASM, whether it exhibits classical G(i)
      coupling, and whether it modulates ASM function. We detected the mRNA encoding
      the dopamine D(2) receptor in total RNA isolated from native human ASM and from
      cultured human airway smooth muscle (HASM) cells. Immunoblots identified the
      dopamine D(2) receptor protein in both native human and guinea pig ASM and
      cultured HASM cells. The dopamine D(2) receptor protein was immunohistochemically
      localized to both human and guinea pig ASM. Acute activation of the dopamine D(2)
      receptor by quinpirole inhibited forskolin-stimulated adenylyl cyclase activity
      in HASM cells, which was blocked by the dopamine D(2) receptor antagonist L
      741626. In contrast, the chronic pretreatment (1 h) with quinpirole potentiated
      forskolin-stimulated adenylyl cyclase activity, which was inhibited by L-741626,
      the phospholipase C inhibitor U73122, or the protein kinase C inhibitor
      GF109203X. Quinpirole also stimulated inositol phosphate synthesis, which was
      inhibited by L-741626 or U73122. Chronic pretreatment (1 h) of the guinea pig
      tracheal rings with quinpirole significantly potentiated forskolin-induced airway
      relaxation, which was inhibited by L-741626. These results demonstrate that
      functional dopamine D(2) receptors are expressed on ASM and could be a novel
      therapeutic target for the relaxation of ASM.

PMID- 21964402
TI  - Studies on the cell biology of interendothelial cell gaps.
AB  - Pain, redness, heat, and swelling are hallmarks of inflammation that were
      recognized as early as the first century AD. Despite these early observations,
      the mechanisms responsible for swelling, in particular, remained an enigma for
      nearly two millennia. Only in the past century have scientists and physicians
      gained an appreciation for the role that vascular endothelium plays in
      controlling the exudation that is responsible for swelling. One of these
      mechanisms is the formation of transient gaps between adjacent endothelial cell
      borders. Inflammatory mediators act on endothelium to reorganize the
      cytoskeleton, decrease the strength of proteins that connect cells together, and
      induce transient gaps between endothelial cells. These gaps form a paracellular
      route responsible for exudation. The discovery that interendothelial cell gaps
      are causally linked to exudation began in the 1960s and was accompanied by
      significant controversy. Today, the role of gap formation in tissue edema is
      accepted by many, and significant scientific effort is dedicated toward
      developing therapeutic strategies that will prevent or reverse the endothelial
      cell gaps that are present during the course of inflammatory illness. Given the
      importance of this field in endothelial cell biology and inflammatory disease,
      this focused review catalogs key historical advances that contributed to our
      modern-day understanding of the cell biology of interendothelial gap formation.

PMID- 21964404
TI  - A role for two-pore K+ channels in modulating Na+ absorption and Cl- secretion in
      normal human bronchial epithelial cells.
AB  - Mucociliary clearance is the primary innate physical defense mechanism against
      inhaled pathogens and toxins. Vectorial ion transport, primarily sodium
      absorption and anion secretion, by airway epithelial cells supports mucociliary
      clearance. This is evidenced by diseases of abnormal ion transport such as cystic
      fibrosis and pseudohypoaldosteronism that are characterized by changes in
      mucociliary clearance. Sodium absorption and chloride secretion in human
      bronchial epithelial cells depend on potassium channel activity, which creates a
      favorable electrochemical gradient for both by hyperpolarizing the apical plasma
      membrane. Although the role of basolateral membrane potassium channels is firmly
      established and extensively studied, a role for apical membrane potassium
      channels has also been described. Here, we demonstrate that bupivacaine and
      quinidine, blockers of four-transmembrane domain, two-pore potassium (K2P)
      channels, inhibit both amiloride-sensitive sodium absorption and forskolin
      stimulated anion secretion in polarized, normal human bronchial epithelial cells
      at lower concentrations when applied to the mucosal surface than when applied to
      the serosal surface. Transcripts from four genes, KCNK1 (TWIK-1), KCNK2 (TREK-1),
      KCNK5 (TASK-2), and KCNK6 (TWIK-2), encoding K2P channels were identified by RT
      PCR. Protein expression at the apical membrane was confirmed by
      immunofluorescence. Our data provide further evidence that potassium channels, in
      particular K2P channels, are expressed and functional in the apical membrane of
      airway epithelial cells where they may be targets for therapeutic manipulation.

PMID- 21964405
TI  - Airway tissue factor-dependent coagulation activity in response to sulfur mustard
      analog 2-chloroethyl ethyl sulfide.
AB  - Acute lung injury is a principal cause of morbidity and mortality in response to
      mustard gas (SM) inhalation. Obstructive, fibrin-containing airway casts have
      recently been reported in a rat inhalation model employing the SM analog 2
      chloroethyl ethyl sulfide (CEES). The present study was designed to identify the
      mechanism(s) causing activation of the coagulation cascade after CEES-induced
      airway injury. Here we report that CEES inhalation elevates tissue factor (TF)
      activity and numbers of detached epithelial cells present in lavage fluid (BALF)
      from rats after exposure (18 h). In vitro studies using 16HBE cells, or with rat
      BALF, indicated that detached epithelial cells could convert factor X (FX) to the
      active form FXa when incubated with factor VII and could elicit rapid clotting of
      plasma. In addition, immunocytochemical analysis demonstrated elevated cell
      surface (TF) expression on CEES-exposed 16HBE cells as a function of time.
      However, total cell TF expression did not increase. Since membrane surfaces
      bearing TF are important determinants of clot initiation, anticoagulants directed
      against these entities were tested for ability to limit plasma clotting or FX
      activation capacity of BALF or culture media. Addition of tifacogin, a TF pathway
      inhibitor, effectively blocked either activity, demonstrating that the
      procoagulant actions of CEES were TF pathway dependent. Lactadherin, a protein
      capable of competing with clotting factors for phospholipid-binding sites, was
      partially effective in limiting these procoagulant actions. These findings
      indicate that TF pathway inhibition could be an effective strategy to prevent
      airway obstruction after SM or CEES inhalation.

PMID- 21964406
TI  - The monocrotaline model of pulmonary hypertension in perspective.
AB  - Severe forms of pulmonary arterial hypertension (PAH) are characterized by
      various degrees of remodeling of the pulmonary arterial vessels, which increases
      the pulmonary vascular resistance and right ventricular afterload, thus
      contributing to the development of right ventricle dysfunction and failure.
      Recent years have seen advances in the understanding of the pathobiology of PAH;
      however, many important questions remain unanswered. Elucidating the pathobiology
      of PAH continues to be critical to design new effective therapeutic strategies,
      and appropriate animal models of PAH are necessary to achieve the task. Although
      the monocrotaline rat model of PAH has contributed to a better understanding of
      vascular remodeling in pulmonary hypertension, we question the validity of this
      model as a preclinically relevant model of severe plexogenic PAH. Here we review
      pertinent publications that either have been forgotten or ignored, and we
      reexamine the monocrotaline model in the context of human forms of PAH.

PMID- 21964408
TI  - New foci of trichinellosis in western Romania, 2011.
AB  - Romania reported the highest incidence of trichinellosis in the world in 2004,
      and the figures continue to be high. This report aims to bring new information
      regarding 2 foci of trichinellosis that occurred in the winter of 2011 in a
      western Romanian region. Data were collected from the outbreak reports and
      hospitalization documents of the patients diagnosed with this condition. Of 22
      patients admitted to hospitals, the medical records were available in 20 cases.
      The mean age of the study group was 37.4+/-13.6 years (range: 3-56) with most of
      them (n=7; 35%) aged 30-39 years old. The majority of the patients (n=19; 95%)
      were adults (>=18 years old), males (n=13; 65%) and rural inhabitants (n=13;
      65%). Mylagia represented the most common clinical symptom (n=17; 85%). All but
      one of the patients had benign and moderately severe courses of the disease. The
      mean eosinophil counts and leukocyte counts were 17+/-10.7% and 10,162.4+/-3798.4
      cells/mm(3), respectively. Re-emergence of trichinellosis in this region has deep
      roots in the population's ancestral customs and education. To limit the
      occurrence of the disease, new and efficient public health strategies should be
      designed and implemented in the nearest future.

PMID- 21964407
TI  - Kv7 potassium channels in airway smooth muscle cells: signal transduction
      intermediates and pharmacological targets for bronchodilator therapy.
AB  - Expression and function of Kv7 (KCNQ) voltage-activated potassium channels in
      guinea pig and human airway smooth muscle cells (ASMCs) were investigated by
      quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), patch
      clamp electrophysiology, and precision-cut lung slices. qRT-PCR revealed
      expression of multiple KCNQ genes in both guinea pig and human ASMCs. Currents
      with electrophysiological and pharmacological characteristics of Kv7 currents
      were measured in freshly isolated guinea pig and human ASMCs. In guinea pig
      ASMCs, Kv7 currents were significantly suppressed by application of the
      bronchoconstrictor agonists methacholine (100 nM) or histamine (30 MUM), but
      current amplitudes were restored by addition of a Kv7 channel activator,
      flupirtine (10 MUM). Kv7 currents in guinea pig ASMCs were also significantly
      enhanced by another Kv7.2-7.5 channel activator, retigabine, and by celecoxib and
      2,5-dimethyl celecoxib. In precision-cut human lung slices, constriction of
      airways by histamine was significantly reduced in the presence of flupirtine. Kv7
      currents in both guinea pig and human ASMCs were inhibited by the Kv7 channel
      blocker XE991. In human lung slices, XE991 induced robust airway constriction,
      which was completely reversed by addition of the calcium channel blocker
      verapamil. These findings suggest that Kv7 channels in ASMCs play an essential
      role in the regulation of airway diameter and may be targeted pharmacologically
      to relieve airway hyperconstriction induced by elevated concentrations of
      bronchoconstrictor agonists.

PMID- 21964409
TI  - PhoP and OxyR transcriptional regulators contribute to Yersinia pestis virulence
      and survival within Galleria mellonella.
AB  - The virulence of Yersinia pestis KIM6+ was compared with multiple isolates of
      Yersinia pseudotuberculosis and Yersinia enterocolitica toward larvae of the
      greater wax moth Galleria mellonella. Although Y. pestis and Y.
      pseudotuberculosis were able to cause lethal infection in G. mellonella, these
      species appeared less virulent than the majority of Y. enterocolitica strains
      tested. Y. pestis survived primarily within hemocytes of G. mellonella, and
      induced a strong antibacterial peptide response that lasted for at least 3 days
      in surviving larvae. Immunization with dead bacteria to induce an antibacterial
      response led to increased survival of the larvae following infection. Mutant
      strains lacking the either phoP or oxyR, which were less resistant to
      antibacterial peptides and hydrogen peroxide respectively, were attenuated and
      restoration of the wild-type genes on plasmids restored virulence. Our results
      indicate that the Y. pseudotuberculosis-Y. pestis lineage is not as virulent
      toward G. mellonella as are the majority of Y. enterocolitica isolates. Further,
      we have shown that G. mellonella is a useful infection model for analyzing Y.
      pestis host-pathogen interactions, and antibacterial peptide resistance mediated
      by phoP and reactive oxygen defense mediated by oxyR are important for Y. pestis
      infection of this insect.

PMID- 21964411
TI  - Mouse tail vertebrae adapt to cyclic mechanical loading by increasing bone
      formation rate and decreasing bone resorption rate as shown by time-lapsed in
      vivo imaging of dynamic bone morphometry.
AB  - It is known that mechanical loading leads to an increase in bone mass through a
      positive shift in the balance between bone formation and bone resorption. How the
      remodeling sites change over time as an effect of loading remains, however, to be
      clarified. The purpose of this paper was to investigate how bone formation and
      resorption sites are modulated by mechanical loading over time by using a new
      imaging technique that extracts three dimensional formation and resorption
      parameters from time-lapsed in vivo micro-computed tomography images. To induce
      load adaptation, the sixth caudal vertebra of C57BL/6 mice was cyclically loaded
      through pins in the adjacent vertebrae at either 8 N or 0 N (control) three times
      a week for 5 min (3000 cycles) over a total of 4 weeks. The results showed that
      mechanical loading significantly increased trabecular bone volume fraction by 20%
      (p<0.001) and cortical area fraction by 6% (p<0.001). The bone formation rate was
      on average 23% greater (p<0.001) and the bone resorption rate was on average 25%
      smaller (p<0.001) for the 8 N group than for the 0 N group. The increase in bone
      formation rate for the 8 N group was mostly an effect of a significantly
      increased surface of bone formation sites (on average 16%, p<0.001), while the
      thickness of bone formation packages was less affected (on average 5% greater,
      p<0.05). At the same time the surface of bone resorption sites was significantly
      reduced (on average 15%, p<0.001), while the depth of resorption pits remained
      the same. For the 8 N group, the strength of the whole bone increased
      significantly by 24% (p<0.001) over the loading period, while the strain energy
      density in the trabecular bone decreased significantly by 24% (p<0.001). In
      conclusion, mouse tail vertebrae adapt to mechanical loading by increasing the
      surface of formation sites and decreasing the surface of resorption sites,
      leading to an overall increase in bone strength. This new imaging technique will
      provide opportunities to investigate in vivo bone remodeling in the context of
      disease and treatment options, with the added value that both bone formation and
      bone resorption parameters can be nondestructively calculated over time.

PMID- 21964410
TI  - Imaging the vasculature by microCT; ain't no bones about it.

PMID- 21964412
TI  - Micro-structural basis for particular vulnerability of the superolateral neck
      trabecular bone in the postmenopausal women with hip fractures.
AB  - In this study we analyzed the trabecular bone micro-architecture in the
      inferomedial and superolateral subregions of the femoral neck in a group with hip
      fractures and a control group of elderly women, with aim to clarify the micro
      structural basis of bone fragility. Proximal femora from 29 Caucasian female
      cadavers were collected at Institute of Forensic Medicine in Belgrade (15 women
      with hip fracture: age 79.5+/-8.5 yrs.; and 14 women without hip fractures: age
      74.1+/-9.3 yrs.). The femoral neck section was scanned in dry conditions using a
      micro-computed tomography (Scanco MUCT 40), at 70 kV, 114 MUA, 300 ms integration
      time, 36 MUm resolution, isotropic, 1024*1024 pixels per slice, automatically
      evaluating trabecular micro-architecture using the built-in program of the micro
      CT with direct 3D morphometry. The samples were foam padded to avoid any movement
      artifacts during scanning. Analysis of the neck section in the fracture group
      compared to the control cases demonstrated significantly lower bone volume
      fraction (mean: 6.3% vs. 11.2%, p=0.002), lower connectivity density (0.33/mm(3)
      vs. 0.74/mm(3), p=0.019) and higher trabecular separation (0.87 mm vs. 0.83 mm,
      p=0.030). Division into the superolateral and inferomedial regions of interest
      revealed that the superolateral neck displayed even more differences in micro
      architectural properties between the fracture and non-fracture groups. Namely,
      while in the inferomedial neck only bone volume fraction and degree of anisotropy
      displayed significant inter-group variability (lower BV/TV with higher degree of
      anisotropy in the fracture group), in the superolateral neck almost all
      parameters were different between the fracture cases and the controls, where the
      fracture group showed a lower trabecular bone volume fraction (3.6% vs. 8.2%,
      p=0.001), lower connectivity (0.21 vs. 0.63/mm(3), p=0.008), more rod like
      trabecular structure (SMI: 2.94 vs. 2.62, p=0.049), higher separation and the
      thinned trabeculae (Tb.Sp: 0.89 vs. 0.85 mm, p=0.013; Tb.Th: 0.17 vs. 0.20 mm,
      p=0.05). In addition, after adjusting for the effects of BV/TV, the majority of
      differences disappeared, demonstrating that the bone loss manifests itself via
      the changes in micro-architectural parameters: trabecular thinning, rising the
      spacing between individual trabeculae, reducing trabecular connectivity and
      accentuating trabecular perforations leading to predominance of rod-like
      trabecular elements. Preferential impairment of the superolateral neck trabecular
      structure and organization in women with hip fracture reveals the region
      dependent micro-structural basis of bone fragility in elderly women.

PMID- 21964413
TI  - Tracking single hematopoietic stem cells in vivo using high-throughput sequencing
      in conjunction with viral genetic barcoding.
AB  - Disentangling cellular heterogeneity is a challenge in many fields, particularly
      in the stem cell and cancer biology fields. Here we demonstrate how to combine
      viral genetic barcoding with high-throughput sequencing to track single cells in
      a heterogeneous population. We use this technique to track the in vivo
      differentiation of unitary hematopoietic stem cells (HSCs). The results are
      consistent with single-cell transplantation studies but require two orders of
      magnitude fewer mice. In addition to its high throughput, the high sensitivity of
      the technique allows for a direct examination of the clonality of sparse cell
      populations such as HSCs. We show how these capabilities offer a clonal
      perspective of the HSC differentiation process. In particular, our data suggest
      that HSCs do not equally contribute to blood cells after irradiation-mediated
      transplantation, and that two distinct HSC differentiation patterns co-exist in
      the same recipient mouse after irradiation. This technique can be applied to any
      virus-accessible cell type for both in vitro and in vivo processes.

PMID- 21964416
TI  - Diverse cellular and physiological roles of phospholipase C-gamma1.

PMID- 21964414
TI  - Comparative genomic analysis of the thermophilic biomass-degrading fungi
      Myceliophthora thermophila and Thielavia terrestris.
AB  - Thermostable enzymes and thermophilic cell factories may afford economic
      advantages in the production of many chemicals and biomass-based fuels. Here we
      describe and compare the genomes of two thermophilic fungi, Myceliophthora
      thermophila and Thielavia terrestris. To our knowledge, these genomes are the
      first described for thermophilic eukaryotes and the first complete telomere-to
      telomere genomes for filamentous fungi. Genome analyses and experimental data
      suggest that both thermophiles are capable of hydrolyzing all major
      polysaccharides found in biomass. Examination of transcriptome data and secreted
      proteins suggests that the two fungi use shared approaches in the hydrolysis of
      cellulose and xylan but distinct mechanisms in pectin degradation.
      Characterization of the biomass-hydrolyzing activity of recombinant enzymes
      suggests that these organisms are highly efficient in biomass decomposition at
      both moderate and high temperatures. Furthermore, we present evidence suggesting
      that aside from representing a potential reservoir of thermostable enzymes,
      thermophilic fungi are amenable to manipulation using classical and molecular
      genetics.

PMID- 21964415
TI  - Extracting a cellular hierarchy from high-dimensional cytometry data with SPADE.
AB  - The ability to analyze multiple single-cell parameters is critical for
      understanding cellular heterogeneity. Despite recent advances in measurement
      technology, methods for analyzing high-dimensional single-cell data are often
      subjective, labor intensive and require prior knowledge of the biological system.
      To objectively uncover cellular heterogeneity from single-cell measurements, we
      present a versatile computational approach, spanning-tree progression analysis of
      density-normalized events (SPADE). We applied SPADE to flow cytometry data of
      mouse bone marrow and to mass cytometry data of human bone marrow. In both cases,
      SPADE organized cells in a hierarchy of related phenotypes that partially
      recapitulated well-described patterns of hematopoiesis. We demonstrate that SPADE
      is robust to measurement noise and to the choice of cellular markers. SPADE
      facilitates the analysis of cellular heterogeneity, the identification of cell
      types and comparison of functional markers in response to perturbations.

PMID- 21964417
TI  - A novel aza-anthrapyrazole blocks the progression of experimental autoimmune
      encephalomyelitis after the priming of autoimmunity.
AB  - Mitoxantrone is one of the few FDA-approved drugs available to treat rapidly
      progressing forms of multiple sclerosis; however, its utilization is compromised
      by a cardiotoxic potential and the risk of mitoxantrone-induced leukemia.
      BBR3378, a novel aza-anthrapyrazole, is structurally similar to mitoxantrone, but
      lacks the ring hydroxyls that may contribute to cardiotoxicity. Here, we
      investigated the therapeutic activity of BBR3378 in a C57BL/6 mouse model of
      multiple sclerosis. Mice given BBR3378, before or after the priming and expansion
      of MOG-specific responses, were protected from ascending paralysis. Strikingly,
      two doses of BBR3378 given a week after EAE induction were sufficient to provide
      significant protection from clinical symptoms and reduce MOG-specific
      proinflammatory T cell cytokine production, and serum IgG responses. Furthermore,
      while mitoxantrone is associated with persistent lymphopenia and cardiotoxicity,
      no such outcomes were detected in BBR3378-treated mice. Our findings show that
      BBR3378 can ameliorate encephalitogenic mechanisms in EAE and antagonize
      underlying autoimmune mechanisms.

PMID- 21964419
TI  - Amino acid functionalized metal-organic frameworks by a soft coupling
      deprotection sequence.
AB  - Covalent post-synthetic modification of a MOF, (In) MIL-68-NH(2), is carried out
      in a novel fashion to immobilize amino acids within the structure. Solid-phase
      peptide coupling methodology opens new perspectives for anchoring chiral bio- and
      catalytically active species. This could facilitate the immobilization of highly
      active and/or coordinating moieties inside MOF cavities.

PMID- 21964418
TI  - Characterization of inhibitory effects of perfluorooctane sulfonate on human
      hepatic cytochrome P450 isoenzymes: focusing on CYP2A6.
AB  - Perfluorooctane sulfonate (PFOS) is a chemically stable compound extensively used
      as oil and water repellent, surface active agents in our daily life. Accumulative
      research evidence gradually appears the toxicity of PFOS against mammals, but the
      whole figure remains to be elucidated. The present study was conducted to know
      the effects of PFOS on human hepatic drug metabolizing-type cytochrome P450 (CYP)
      isoenzymes such as CYP1A2 (7-ethoxyresorufin as a substrate), CYP2A6 (coumarin),
      CYP2B6 (7-ethoxy-4-trifluoromethylcoumarin), CYP2C8 (paclitaxel), CYP2C9
      (diclofenac), CYP2C19 (S-mephenytoin), CYP2D6 (bufuralol), CYP2E1 (chlorzoxazone)
      and CYP3A4 (testosterone) in human livers employing their typical substrates.
      Although all of the oxidation reactions tested were more or less inhibited by
      PFOS, diclofenac 4'-hydroxylation mediated mainly by CYP2C9 was most strongly
      inhibited (K(i) value of 40 nM), followed by paclitaxel 6alpha-hydroxylation
      mediated mainly by CYP2C8 (K(i) value of 4 MUM). The substrate oxidation
      reactions catalyzed by CYP2A6, CYP2B6, CYP2C19 and CYP3A4 were moderately (K(i)
      values of 35 to 45 MUM), and those by CYP1A2, CYP2D6 and CYP2E1 were weakly
      inhibited by PFOS (K(i) values of 190-300 MUM). The inhibition by PFOS for
      coumarin 7-hydroxylation mainly catalyzed by human liver microsomal CYP2A6 as
      well as by the recombinant enzyme was found to be enhanced by the preincubation
      of PFOS with human liver microsomes and NADPH as compared to the case without
      preincubation. The inhibition of the human liver microsomal cumarin 7
      hydroxylation was PFOS concentration-dependent, and exhibited pseudo-first-order
      kinetics with respect to preincubation time, yielding K(inact) and K(I) values of
      0.06 min(-1) and 23 MUM, respectively. These results suggest that the metabolism
      of medicines which are substrates for CYP2C9 may be altered by PFOS in human
      bodies, and that PFOS is a mechanism-based inhibitor of CYP2A6.

PMID- 21964421
TI  - Impact of low-level thyroid hormone disruption induced by propylthiouracil on
      brain development and function.
AB  - The critical role of thyroid hormone (TH) in brain development is well
      established. Evidence shows that severe deficiencies lead to significant
      neurological dysfunction. Much less information is available on more modest
      perturbations of TH on brain function. The present study induced varying degrees
      of developmental hypothyroidism by administration of low doses of the TH
      synthesis inhibitor, propylthiouracil (PTU 0, 1, 2, and 3 ppm) to the drinking
      water of pregnant rats. This regimen produced dose-dependent reductions in
      circulating levels of T4 in dams and offspring on postnatal days (PN) 15 and 22,
      with return to control levels in adulthood upon termination of treatment at
      weaning. Modest reductions in T3 were observed in the high-dose group on PN15.
      Synaptic function in the dentate gyrus was examined in adult euthyroid offspring
      using in vivo field potentials. Excitatory synaptic transmission (excitatory
      postsynaptic potential [EPSP] slope amplitude) was significantly reduced at 2 and
      3 ppm PTU, with no statistically reliable effect detected in the population
      spike. Paired-pulse functions estimating the integrity of inhibitory synaptic
      processing were modestly reduced by 3 ppm PTU. Long-term potentiation (LTP) of
      the EPSP slope was impaired at all dose levels. Trace fear conditioning to
      context and to cue was impaired at the highest dose level when a distractor
      stimulus was present, whereas conditioning in a standard trace fear paradigm
      paradoxically revealed "enhanced" performance at the intermediate dose and a
      return to control values in the high-dose group. Biphasic dose-response profiles
      were evident in some measures (trace fear conditioning and LTP) but not others
      and serve to exemplify the complexity of the role of TH in brain development and
      its consequences for brain function.

PMID- 21964420
TI  - Comparative metabolomic and genomic analyses of TCDD-elicited metabolic
      disruption in mouse and rat liver.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) elicits a broad spectrum of species
      specific effects that have not yet been fully characterized. This study compares
      the temporal effects of TCDD on hepatic aqueous and lipid metabolite extracts
      from immature ovariectomized C57BL/6 mice and Sprague-Dawley rats using gas
      chromatography-mass spectrometry and nuclear magnetic resonance-based metabolomic
      approaches and integrates published gene expression data to identify species
      specific pathways affected by treatment. TCDD elicited metabolite and gene
      expression changes associated with lipid metabolism and transport, choline
      metabolism, bile acid metabolism, glycolysis, and glycerophospholipid metabolism.
      Lipid metabolism is altered in mice resulting in increased hepatic
      triacylglycerol as well as mono- and polyunsaturated fatty acid (FA) levels.
      Mouse-specific changes included the induction of CD36 and other cell surface
      receptors as well as lipases- and FA-binding proteins consistent with hepatic
      triglyceride and FA accumulation. In contrast, there was minimal hepatic fat
      accumulation in rats and decreased CD36 expression. However, choline metabolism
      was altered in rats, as indicated by decreases in betaine and increases in
      phosphocholine with the concomitant induction of betaine-homocysteine
      methyltransferase and choline kinase gene expression. Results from these studies
      show that aryl hydrocarbon receptor-mediated differential gene expression could
      be linked to metabolite changes and species-specific alterations of biochemical
      pathways.

PMID- 21964422
TI  - Evaluation of novel high-throughput embryonic stem cell tests with new molecular
      markers for screening embryotoxic chemicals in vitro.
AB  - The embryonic stem cell test (EST) is a validated in vitro alternative test for
      prediction of embryotoxicity with inhibition of cardiomyocyte differentiation
      under the microscope as beating areas at day 10 as an endpoint. However,
      improvements are necessary for regulatory acceptance and application to high
      throughput screening. We have previously reported that heart and neural crest
      derivatives expressed transcript 1 (Hand1), a transcription factor essential for
      mammalian heart development, and cardiomyopathy associated 1 (Cmya1), an
      intercalated disk protein implicated in cardiac morphogenesis, are quantitative
      and objective molecular endpoints for predicting embryotoxicity, detected at day
      6 when mouse embryonic stem (ES) cells differentiate into cardiomyocytes. In
      established stable transgenic ES cells with Hand1 or Cmya1 promoters upstream of
      luciferase reporter gene, changes in each gene expression were found to be
      coincident with those in luciferase activities during cardiomyocyte
      differentiation, suggesting that monitoring might be possible by chemiluminescent
      determination. In our novel EST, differentiation toxicity and cytotoxicity of
      test chemicals were here analyzed using ES cells and 3T3 fibroblasts by this
      approach in 96-microwell plates. Extensive investigations were performed to
      explore predictive power and validity by comparing a set of 24 well-known test
      chemicals. The novel EST offers high predictability and accuracy with a reduced
      test duration and manpower compared with the original EST protocol, thus
      providing a new rapid and sensitive in vitro method for screening
      embryotoxicants.

PMID- 21964424
TI  - Crossvalidation of two heart rate-based equations for predicting VO2max in white
      and black men.
AB  - The purpose of this investigation was to crossvalidate 2 equations that use the
      ratio of maximal heart rate (HRmax) to resting HR (HRrest) for predicting maximal
      oxygen consumption (VO2max) in white and black men. One hundred and nine white (n
      = 51) and black (n = 58) men completed a maximal exercise test on a treadmill to
      determine VO2max. The HRrest and HRmax were used to predict VO2max via the
      HRindex and HRratio equations. Validity statistics were done to compare the
      criterion versus predicted VO2max values across the entire cohort and within each
      race separately. For the entire group, VO2max was significantly overestimated
      with the HRindex equation, but the HRratio equation yielded no significant
      difference compared with the criterion. In addition, there were no significant
      differences shown between VO2max and either HR-based prediction equation for the
      white subgroup. However, both equations significantly overestimated VO2max in the
      black group. Furthermore, large standard error of estimates (ranging from 6.92 to
      7.90 ml.kg(-1).min(-1)), total errors (ranging from 8.30 to 8.62 ml.kg(-1).min(
      1)), and limits of agreement (ranging from upper limits of 16.65 to lower limits
      of -18.25 ml.kg(-1).min(-1)) were revealed when comparing the predicted to
      criterion VO2max for both the groups. Considering the results of this
      investigation, the HRratio and HRindex methods appear to crossvalidate and prove
      useful for estimating the mean VO2max in white men as a group but not for an age
      matched group of black men. However, because of inflated values for error,
      caution should be exercised when using these methods to predict individual
      VO2max.

PMID- 21964423
TI  - Aerosolized ZnO nanoparticles induce toxicity in alveolar type II epithelial
      cells at the air-liquid interface.
AB  - The majority of in vitro studies characterizing the impact of engineered
      nanoparticles (NPs) on cells that line the respiratory tract were conducted in
      cells exposed to NPs in suspension. This approach introduces processes that are
      unlikely to occur during inhaled NP exposures in vivo, such as the shedding of
      toxic doses of dissolved ions. ZnO NPs are used extensively and pose significant
      sources for human exposure. Exposures to airborne ZnO NPs can induce adverse
      effects, but the relevance of the dissolved Zn(2+) to the observed effects in
      vivo is still unclear. Our goal was to mimic in vivo exposures to airborne NPs
      and decipher the contribution of the intact NP from the contribution of the
      dissolved ions to airborne ZnO NP toxicity. We established the exposure of
      alveolar type II epithelial cells to aerosolized NPs at the air-liquid interface
      (ALI) and compared the impact of aerosolized ZnO NPs and NPs in suspension at the
      same cellular doses, measured as the number of particles per cell. By evaluating
      membrane integrity and cell viability 6 and 24 h post-exposure, we found that
      aerosolized NPs induced toxicity at the ALI at doses that were in the same order
      of magnitude as doses required to induce toxicity in submersed cultures. In
      addition, distinct patterns of oxidative stress were observed in the two exposure
      systems. These observations unravel the ability of airborne ZnO NPs to induce
      toxicity without the contribution of dissolved Zn(2+) and suggest distinct
      mechanisms at the ALI and in submersed cultures.

PMID- 21964425
TI  - Relationship between functional movement screen and athletic performance.
AB  - Parchmann, CJ and McBride, JM. Relationship between functional movement screen
      and athletic performance. J Strength Cond Res 25(12): 3378-3384, 2011-Tests such
      as the functional movement screen (FMS) and maximal strength (repetition maximum
      strength [1RM]) have been theorized to assist in predicting athletic performance
      capabilities. Some data exist concerning 1RM and athletic performance, but very
      limited data exist concerning the potential ability of FMS to assess athletic
      performance. The purpose of this investigation was to determine if FMS scores or
      1RM is related to athletic performance, specifically in Division I golfers in
      terms of sprint times, vertical jump (VJ) height, agility T-test times, and club
      head velocity. Twenty-five National Collegiate Athletic Association Division I
      golfers (15 men, age = 20.0 +/- 1.2 years, height = 176.8 +/- 5.6 cm, body mass =
      76.5 +/- 13.4 kg, squat 1RM = 97.1 +/- 21.0 kg) (10 women, age = 20.5 +/- 0.8
      years, height = 167.0 +/- 5.6 cm, body mass = 70.7 +/- 21.5 kg, squat 1RM = 50.3
      +/- 16.6) performed an FMS, 1RM testing, and field tests common in assessing
      athletic performance. Athletic performance tests included 10- and 20-m sprint
      time, VJ height, agility T-test time, and club head velocity. Strength testing
      included a 1RM back squat. Data for 1RM testing were normalized to body mass for
      comparisons. Correlations were determined between FMS, 1RMs, and athletic
      performance tests using Pearson product correlation coefficients (p <= 0.05). No
      significant correlations existed between FMS and 10-m sprint time (r = -0.136),
      20-m sprint time (r = -0.107), VJ height (r = 0.249), agility T-test time (r = 
      0.146), and club head velocity (r = -0.064). The 1RM in the squat was
      significantly correlated to 10-m sprint time (r = -0.812), 20-m sprint time (r = 
      0.872), VJ height (r = 0.869), agility T-test time (r = -0.758), and club head
      velocity (r = 0.805). The lack of relationship suggests that FMS is not an
      adequate field test and does not relate to any aspect of athletic performance.
      Based on the data from this investigation, 1RM squat strength appears to be a
      good indicator of athletic performance.

PMID- 21964426
TI  - Match running performance and exercise intensity in elite female Rugby Sevens.
AB  - The purpose of this study was to describe the match-play demands of professional
      female rugby players competing in Rugby Sevens (Rugby 7's) matches. Time-motion
      analyses (global position system) were performed on 12 elite female rugby players
      during 5 competitive matches in a 2-day international tournament. Data revealed
      that players covered an average distance of 1,556.2 +/- 189.3 m per game (14
      minutes). Over this distance, 29.7% (462.6 +/- 94.6 m) was spent standing and
      walking, 33.2% (515.9 +/- 88.6 m) jogging, 11.6% (181.0 +/- 61.4 m) cruising,
      16.4% (255.7 +/- 88.3 m) striding, 3.7% (57.1 +/- 40.8 m) high-intensity running,
      and 5.4% (84.0 +/- 64.8 m) sprinting. The average maximal distance of sprints,
      number of sprints, minimum distance of sprint, and mean sprint distance over the
      game were as follows: 25.8 +/- 16.1 m, 5.3 +/- 3.2 sprints, 6.5 +/- 2.0 m, and
      17.2 +/- 8.8 m, respectively. The players' work-to-rest ratio was 1:0.4. For over
      75% of the game, the players were exposed to heart rates (HRs) >80% of their
      maximal HR. There were no statistical differences between the first and second
      halves in any of the variables analyzed. This study suggests that the physical
      demands of Rugby 7's are quite different from those reported in other rugby
      codes. For players and teams to remain competitive in female Rugby Sevens,
      coaching, conditioning, and physical fitness testing should reflect these current
      demands.

PMID- 21964427
TI  - The validity of multifrequency bioelectrical impedance measures to detect changes
      in the hydration status of wrestlers during acute dehydration and rehydration.
AB  - The objective of this study was to examine the validity of multifrequency direct
      segmental bioelectrical impedance analysis (DSM-BIA) measures to detect changes
      in the hydration status of wrestlers after they underwent 3% acute dehydration
      and a 2-hour rehydration period. Fifty-six National Collegiate Athletic
      Association wrestlers: (mean +/- SEM); age 19.5 +/- 0.2 years, height 1.73 +/-
      0.01 m, and body mass (BM) 82.5 +/- 2.3 kg were tested in euhydrated, dehydrated
      (-3.5%), and 2-hour rehydration conditions using DSM-BIA to detect the changes in
      hydration status. The hydration status was quantified by measuring the changes in
      plasma osmolality (P(osm)), urine osmolality (Uosm), urine specific gravity
      (U(sg)), BM, and weighted segmental impedance at frequencies of 5, 20, 50, 100,
      and 500 kHz. Weighted segmental impedance significantly increased after a 3.5%
      reduction in the body weight for all the 5 frequencies evaluated, but it did not
      return to baseline at 2-hour rehydration. P(osm) (303 +/- 0.6 mOsm.L(-1)), Uosm
      (617 +/- 47 mOsm.L(-1)), and U(sg) (1.017 +/- 0.001) all significantly increased
      at postdehydration and returned to baseline at 2-hour rehydration. Estimations of
      extracellular water were significantly different throughout the trial, but there
      were no significant changes in the estimations of the total body water or
      intracellular water. The results of this study demonstrate the potential use of
      DSM-BIA as a field measure to assess the hydration status of wrestlers for the
      purpose of minimal weight certification before the competitive season. When
      employing DSM-BIA to assess the hydration status, the results indicated that the
      changes in weighted segmental impedance at the frequencies evaluated (5, 20, 50,
      100, and 500 kHz) are sensitive to acute changes in dehydration but lag behind
      changes in the standard physiological (plasma and urinary) markers of hydration
      status after a 2-hour rehydration period.

PMID- 21964428
TI  - Sodium bicarbonate supplementation and ingestion timing:  does it matter?
AB  - Although a considerable amount of literature exists on the ergogenic potential of
      ingesting sodium bicarbonate (NaHCO3) before short-term, high-intensity exercise,
      very little exists on optimal loading times before exercise. The purpose of this
      study was to determine the influence of NaHCO3 supplementation timing on repeated
      sprint ability (RSA). Eight men completed 3 (randomized and counterbalanced)
      trials of ten 10-second sprints separated by 50 seconds of active recovery (1:5
      work-to-rest) on a nonmotorized treadmill. Before each trial, the subjects
      ingested 0.3 g.kg(-1) body weight of NaHCO3 at 60 (H1), 120 (H2), or 180 (H3)
      minutes before exercise. Additionally, the subjects were assessed for any side
      effects (gastrointestinal [GI] discomfort) from the NaHCO3 ingestion via a visual
      analog scale (VAS). Blood buffering was assessed using a 2-way analysis of
      variance (ANOVA) with repeated measures, whereas repeated sprint performance and
      GI discomfort were assessed via a 1-way ANOVA with repeated measures. Blood
      buffering capacity was not different at preexercise times (HCO3(-) [millimoles
      per liter] H1: 30.2 +/- 0.4, H2: 30.9 +/- 0.6, H3: 31.2 +/- 0.6; p > 0.74).
      Average speed, average power, and total distance covered progressively declined
      over the 10 sprints; however, there was no difference between conditions (p >
      0.22). The incidence of GI discomfort was significantly higher (p < 0.05) from
      preingestion at all time points with the exception of 180 minutes, whereas
      severity was only different between 90 and 180 minutes. Ingestion times (between
      60 and 180 minutes) did not influence the blood buffering or the ergogenic
      potential of NaHCO3 as assessed by RSA. However, VAS scores indicated that at 180
      minutes postingestion, an individual is less prone to experiencing significant GI
      discomfort.

PMID- 21964429
TI  - Spectral properties of H-reflex recordings after an acute bout of whole-body
      vibration.
AB  - Although research supports the use of whole-body vibration (WBV) to improve
      neuromuscular performance, the mechanisms for these improvements remain unclear.
      The purpose of this study was to identify the effect of WBV on the spectral
      properties of electrically evoked H-reflex recordings in the soleus (SOL) muscle.
      The H-reflex recordings were measured in the SOL muscle of 20 participants before
      and after a bout of WBV. The H-reflexes were evoked every 15 seconds for 150
      seconds after WBV. A wavelet procedure was used to extract spectral data, which
      were then quantified with a principle components analysis. Resultant principle
      component scores were used for statistical analysis. The analysis extracted 1
      principle component associated with the intensity of the myoelectric spectra and
      1 principle component associated with the frequency. The scores of the principle
      component that were related to the myoelectric intensity were smaller at 30 and
      60 milliseconds after WBV than before WBV. The WBV transiently decreased the
      intensity of myoelectric spectra during electrically evoked contractions, but it
      did not influence the frequency of the spectra. The decrease in intensity likely
      indicates a smaller electrically evoked muscle twitch response, whereas the lack
      of change in frequency would indicate a similar recruitment pattern of motor
      units before and after WBV.

PMID- 21964430
TI  - Is it the athlete or the equipment? An analysis of the top swim performances from
      1990 to 2010.
AB  - O'Connor, LM and Vozenilek, JA. Is it the athlete or the equipment? An analysis
      of the top swim performances from 1990 to 2010. J Strength Cond Res 25(12): 3239
      3241, 2011-Forty-three world record swims were recorded at the 2009 Federation
      Internationale de Natation (FINA) World Championship meet in Rome. Of the 20 FINA
      recognized long-course (50-m pool) swimming events, men set new world records in
      15 of those events, whereas women did the same in 17 events. Each of the men's
      world records and 14 of the 17 women's records still stand. These performances
      were unprecedented; never before had these many world records been broken in such
      a short period of time. There was much speculation that full-body, polyurethane,
      technical swimsuits were the reason for the conspicuous improvement in world
      records. Further analysis led the FINA to institute new rules on January 1, 2010,
      that limited the types of technical swimsuits that could be worn by athletes. No
      long-course world record has been broken since then. We sought to understand this
      phenomenon by analyzing publicly available race data and exploring other possible
      causes including improvements in other sports, improvements in training science,
      changes in rules and regulations, gender differences, anaerobic vs. aerobic
      events, unique talent, and membership data.

PMID- 21964431
TI  - A 18F-fluorodeoxyglucose MicroPET imaging study to assess changes in brain
      glucose metabolism in a rat model of surgery-induced latent pain sensitization.
AB  - BACKGROUND: Neuroplastic changes involved in latent pain sensitization after
      surgery are poorly defined. We assessed temporal changes in glucose brain
      metabolism in a postoperative rat model using positron emission tomography. We
      also investigated brain metabolism after naloxone administration. METHODS: Rats
      were given remifentanil anesthetic and underwent a plantar incision, with 1 mg/kg
      of (-)-naloxone subcutaneously administered on postoperative days 20 and 21.
      Using the von Frey test, mechanical thresholds were measured pre- and
      postoperatively at different time points in awake animals during F
      fluorodeoxyglucose (F-FDG) uptake. Brain images were also obtained the day before
      mechanical testing, using a positron emission tomography R4 scanner (Concorde
      Microsystems, Siemens, Knoxville, TN). Differences in brain activity were
      assessed utilizing a statistical parametric mapping. RESULTS: Surgery induced
      minor changes in F-FDG uptake in the cerebellum, hippocampus, and posterior
      cortex, which extended to the thalamus, hypothalamus, and brainstem on days 6 and
      7. Changes were still present on day 21. Maximal postoperative hypersensitivity
      was observed on day 2. The administration of (-)-naloxone on day 21 induced
      significant hypersensitivity, greatly enhancing the effect on F-FDG uptake. In
      sham-operated rats, naloxone induced changes limited to the striatum and the
      cerebellum. Nonnociceptive stimulation with von Frey filaments had no effect on F
      FDG uptake. CONCLUSIONS: Surgery, remifentanil, and their combination induced
      long-lasting and significant metabolic changes in the pain brain matrix, with a
      positive correlation with hypersensitivity after naloxone. Changes in brain F-FDG
      precipitated by naloxone suggest that surgery under remifentanil anesthetic
      induces the greatest neuroplastic brain adaptations in opioid-related pathways
      involved in nociceptive processing and long-lasting pain sensitization.

PMID- 21964432
TI  - Major histocompatibility complex and strong human leukocyte antigen-DRB1 and
      gender association with Vogt-Koyanagi-Harada syndrome in Mexican Mestizos.
AB  - Vogt-Koyanagi-Harada syndrome (VKH) is a multisystem autoimmune disorder mediated
      by cytotoxic T cells targeting melanocytes antigen(s). A strong major
      histocompatibility complex (MHC) association with HLA-DRB1*04:05 has been
      demonstrated in different populations. We investigated the contribution of HLA
      A*, -B*, -C*, -DRB1*, and -DQB1* genes, belonging to the human leukocyte antigen
      (HLA), to the expression of VKH and we analyzed the influence of gender on the
      HLA association. A total of 76 patients and 256 healthy Mexican Mestizo
      individuals were included. HLA-A, B, C, and DQB1 typing was performed using the
      polymerase chain reaction, and hybridization was done using sequence specific
      probes. DRB1 alleles were defined by means of sequence base typing. The frequency
      of DRB1*04:05 (odds ratio=2.95) and DRB1*04:04 (odds ratio=2.79) were found to be
      significantly increased in the patients, conferring a similar risk. Gender
      stratification analysis showed that these alleles were associated with female
      gender only. No HLA class I or class II alleles were significantly deviated in
      males. The frequency of DRB1*04:07 was increased in the whole group, upon
      withdrawal from analysis the DRB1*04:04 and *04:05 positive patients. A trend of
      DRB1 alleles contributing to the expression of VKH is suggested:
      DRB1*04:05=*04:04>*04:07>*01:01>*01:02. Although none of the results were
      significant after the p value was corrected, the data are consistent with those
      in numerous other studies, suggesting that several different DRB1* alleles may be
      involved in the etiopathogenesis of the disease by presenting an overlapping set
      of ocular peptides to the T cells, which in turn may trigger the autoimmune
      response that is present in the patients.

PMID- 21964434
TI  - Prenatal fluoxetine exposure induces life-long serotonin 5-HT3 receptor-dependent
      cortical abnormalities and anxiety-like behaviour.
AB  - Selective serotonin reuptake inhibitors (SSRIs) are the first choice of drugs to
      treat depression and anxiety during pregnancy. However, there is evidence that in
      utero exposure to SSRIs leads to adverse effects in offspring. Here we show that
      in mice, the adverse effects of the widely used antidepressant and SSRI
      fluoxetine are critically dependent on the 5-HT(3) receptor, the only ligand
      gated ion channel in the family of serotonin receptors. In utero exposure to
      fluoxetine induces anxiety-like behavior in wildtype, but not in mice lacking the
      5-HT(3) receptor. In addition to this behavioral phenotype, these mice show life
      long abnormalities of cortical cytoarchitecture, which can be reversed in vitro
      by pharmacological block of 5-HT(3) receptors. Moreover, the effect of fluoxetine
      on the development of cortical neurons is absent in 5-HT(3) receptor knockout
      mice. These findings pinpoint the pivotal role of serotonergic signaling during
      development and provide a novel basis to investigate the adverse effects of the
      use of fluoxetine during pregnancy. This article is part of a Special Issue
      entitled 'Post-Traumatic Stress Disorder'.

PMID- 21964433
TI  - A Protein Epitope Signature Tag (PrEST) library allows SILAC-based absolute
      quantification and multiplexed determination of protein copy numbers in cell
      lines.
AB  - Mass spectrometry-based proteomics increasingly relies on relative or absolute
      quantification. In relative quantification, stable isotope based methods often
      allow mixing at early stages of sample preparation, whereas for absolute
      quantification this has generally required recombinant expression of full length,
      labeled protein standards. Here we make use of a very large library of Protein
      Epitope Signature Tags (PrESTs) that has been developed in the course of the
      Human Protein Atlas Project. These PrESTs are expressed recombinantly in E. coli
      and they consist of a short and unique region of the protein of interest as well
      as purification and solubility tags. We first quantify a highly purified, stable
      isotope labeling of amino acids in cell culture (SILAC)-labeled version of the
      solubility tag and use it determine the precise amount of each PrEST by its SILAC
      ratios. The PrESTs are then spiked into cell lysates and the SILAC ratios of
      PrEST peptides to peptides from endogenous target proteins yield their cellular
      quantities. The procedure can readily be multiplexed, as we demonstrate by
      simultaneously determining the copy number of 40 proteins in HeLa cells. Among
      the proteins analyzed, the cytoskeletal protein vimentin was found to be most
      abundant with 20 million copies per cell, while the transcription factor and
      oncogene FOS only had 6000 copies. Direct quantification of the absolute amount
      of single proteins is possible via a SILAC experiment in which labeled cell
      lysate is mixed both with the heavy labeled solubility tag and with the
      corresponding PrEST. The SILAC-PrEST combination allows accurate and streamlined
      quantification of the absolute or relative amount of proteins of interest in a
      wide variety of applications.

PMID- 21964435
TI  - Accumbal dopamine D2 receptor function is associated with individual variability
      in ethanol behavioral sensitization.
AB  - Striatal dopamine D2 receptors have been implicated in the development of
      behavioral sensitization after repeated exposure to drugs of abuse. There are
      clear individual differences in the level of sensitization to ethanol among
      species and even among individuals from the same strain. Albino Swiss mice
      treated with ethanol (2.2 g/kg) have been shown to present clear variations in
      the development of sensitization. While some mice developed ethanol (EtOH)
      induced sensitization, others did not. This variability was associated with
      differences in D2 dopaminergic receptor binding. In the present study, we
      evaluated the functional relevance of dopamine D2 receptor by measuring, in
      sensitized and non-sensitized mice, the locomotor response to a D2 receptor
      agonist (quinpirole, 0.5 and 2.0 mg/kg i.p. or 0.01 and 0.2 MUg/side intra
      accumbens) or antagonist (sulpiride, 10 or 50 mg/kg i.p. or 0.02 MUg/side intra
      accumbens + ethanol i.p.). Whereas the systemic administration of quinpirole
      decreased locomotor activity in a similar way in all the groups, intra-nucleus
      accumbens (NAc) administration induced significantly higher locomotor stimulation
      in the sensitized group alone. Our data show that functionally hyperresponsive D2
      receptors are present in the NAcs of sensitized but not non-sensitized mice,
      suggesting that this could be a biomarker of behavioral sensitization.
      Furthermore, i.p. administration of sulpiride blocked the expression of
      sensitization in the sensitized group, and intra-NAc administration attenuated
      it, indicating that the activation of accumbal D2 receptors is essential for the
      expression of EtOH behavioral sensitization. This article is part of a Special
      Issue entitled 'Post-Traumatic Stress Disorder'.

PMID- 21964437
TI  - Optimisation of expression and purification of the feline and primate foamy virus
      transmembrane envelope proteins using a 96 deep well screen.
AB  - The production of recombinant transmembrane proteins is due to their biochemical
      properties often troublesome and time consuming. Here the prokaryotic expression
      and purification of the transmembrane envelope proteins of the feline and primate
      foamy viruses using a screening assay for optimisation of expression in 96 deep
      well plates is described. Testing simultaneously various bacterial strains,
      media, temperatures, inducer concentrations and different transformants,
      conditions for an about twentyfold increased production were quickly determined.
      These small scale test conditions could be easily scaled up, allowing
      purification of milligram amounts of recombinant protein. Proteins with a purity
      of about 95% were produced using a new purification protocol, they were
      characterised by gel filtration and circular dichroism and successfully applied
      in immunological assays screening for foamy virus infection and in immunisation
      studies. Compared to the previously described protocol (M. Muhle, A. Bleiholder,
      S. Kolb, J. Hubner, M. Lochelt, J. Denner, Immunological properties of the
      transmembrane envelope protein of the feline foamy virus and its use for
      serological screening, Virology 412 (2011) 333-340), proteins with similar
      characteristics but about thirtyfold increased yields were obtained. The
      screening and production method presented here can also be applied for the
      production of transmembrane envelope proteins of other retroviruses, including
      HIV-1.

PMID- 21964436
TI  - Recombinant human MFG-E8 attenuates cerebral ischemic injury: its role in anti
      inflammation and anti-apoptosis.
AB  - Excessive inflammation and apoptosis contribute to the pathogenesis of ischemic
      stroke. MFG-E8 is a 66-kDa glycoprotein that has shown tissue protection in
      various models of organ injury. However, the potential role of MFG-E8 in cerebral
      ischemia has not been investigated. We found that levels of MFG-E8 protein in the
      brain were reduced at 24 h after cerebral ischemia. To assess the potential role
      of MFG-E8 in cerebral ischemia, adult male Sprague-Dawley rats were subjected to
      permanent middle cerebral artery occlusion (MCAO). At 1 h post-stroke onset, an
      intravenous administration of 1 ml saline as vehicle or 160 MUg/kg BW recombinant
      human MFG-E8 (rhMFG-E8) as treatment was given. The optimal dose of rhMFG-E8 was
      obtained from previous dose-response organ protection in rat sepsis studies.
      Neurological scores were determined at 24 h and 48 h post-MCAO. Rats were
      sacrificed thereafter and brains rapidly removed and analyzed for infarct size,
      histopathology, and markers of inflammation and apoptosis. Compared with saline
      vehicle, rhMFG-E8 treatment led to significant decreases in sensorimotor and
      vestibulomotor deficits, and infarct size at 24 h and 48 h post-MCAO. Measures
      associated with improved outcome included reduced microglial inflammatory
      cytokine secretion, adhesion molecules and neutrophil influx, cleaved caspase-3,
      and upregulation of peroxisome proliferator activated receptor-gamma (PPAR
      gamma), and Bcl-2/Bax ratio leading to decreased apoptosis. Thus, rhMFG-E8
      treatment is neuroprotective against cerebral ischemia through suppression of
      inflammation and apoptosis. This article is part of a Special Issue entitled
      'Post-Traumatic Stress Disorder'.

PMID- 21964438
TI  - Crosstalk between Raf/MEK/ERK and PI3K/AKT in suppression of Bax conformational
      change by Grp75 under glucose deprivation conditions.
AB  - During glucose deprivation (GD)-induced cellular stress, the molecular chaperone
      glucose-regulated protein 75 (Grp75)/Mortalin/PBP74/mtHSP70 (hereafter termed
      "Grp75") plays an important role in the suppression of apoptosis by inhibiting
      the Bax conformational change that delays the release of cytochrome c. The
      molecular pathways by which it carries out these functions are still unclear. We
      hypothesize that the anti-apoptotic effect by the overexpression of Grp75 was
      through the signal of AKT activated by classic phosphoinositide 3-kinase (PI3K)
      and also involved PI3K-independent pathways. Using the PC12 cell GD model, we
      demonstrated a novel mechanism of Grp75 activating AKT, which may be PI3K
      independent and associated with Raf/MEK (mitogen-activated protein kinase/ERK
      kinase)/ERK signaling. The PI3K inhibitor LY294002 did not influence the
      activation of AKT by the Grp75 overexpression under GD; however, the MEK
      inhibitor U0126 dramatically inhibited AKT phosphorylation in the same assay. In
      addition to the PI3K/AKT signal pathway, Grp75 overexpression also inhibited the
      Bax conformational change through the Raf/MEK/ERK signal pathway. In conclusion,
      Grp75 overexpression in activating AKT can be PI3K independent and associated
      with Raf/MEK/ERK signaling under GD. At the same time, PI3K may also crosstalk
      with Raf-1, in which the prosurvival signal of PI3K maintains the expression of
      Raf-1. The activated AKT and extracellular signal-regulated protein kinases 1 and
      2 by Grp75 inhibited the Bax conformational change and subsequent apoptosis.

PMID- 21964440
TI  - Premature antibodies with rapid reaction kinetics and their characterization for
      diagnostic applications.
AB  - In this study, rapidly reversible antibodies were produced and the binding
      kinetics, stability, and utility as an analytical binder were evaluated. The
      number of times the animals were immunized with the antigen (myoglobin as marker
      for acute myocardial infarction [AMI]) was limited to two, increasing the chances
      of producing premature antibodies that rapidly reacted with the binding partner
      in both association and dissociation. The rate constants were higher than
      1*10(6)M(-1)s(-1) and 1*10(-3)s(-1), respectively, and the affinity exceeded
      10(8)M(-1). They responded to an abrupt environmental change (acidic pH in this
      study) where the reaction kinetics was changed to slow binding, particularly for
      dissociation, resulting in a 10-fold increase in affinity. The binding
      characteristic before and after the transition were stable at 37 degrees C for
      longer than 1 month, suggesting that the rapidly reversible antibody was the
      intermediate of the slow binder. The rapid kinetic antibody was used as the
      primary binder in the conventional competitive immunoassay, which displayed a
      lower sensitivity than the transformed antibody due to its lower affinity. We
      further demonstrated that, on combination with a microfluidic label-free sensor,
      the reaction could be continuously monitored in serum medium by recycling the
      same antibody without employing the regeneration step.

PMID- 21964439
TI  - Phosphatidylserine is polarized and required for proper Cdc42 localization and
      for development of cell polarity.
AB  - Polarity is key to the function of eukaryotic cells. On the establishment of a
      polarity axis, cells can vectorially target secretion, generating an asymmetric
      distribution of plasma membrane proteins. From Saccharomyces cerevisiae to
      mammals, the small GTPase Cdc42 is a pivotal regulator of polarity. We used a
      fluorescent probe to visualize the distribution of phosphatidylserine in live S.
      cerevisiae. Remarkably, phosphatidylserine was polarized in the plasma membrane,
      accumulating in bud necks, the bud cortex and the tips of mating projections.
      Polarization required vectorial delivery of phosphatidylserine-containing
      secretory vesicles, and phosphatidylserine was largely excluded from endocytic
      vesicles, contributing to its polarized retention. Mutants lacking
      phosphatidylserine synthase had impaired polarization of the Cdc42 complex,
      leading to a delay in bud emergence, and defective mating. The addition of
      lysophosphatidylserine resulted in resynthesis and polarization of
      phosphatidylserine, as well as repolarization of Cdc42. The results indicate that
      phosphatidylserine--and presumably its polarization--are required for optimal
      Cdc42 targeting and activation during cell division and mating.

PMID- 21964441
TI  - Endogenous Bmp4 in myoblasts is required for myotube formation in C2C12 cells.
AB  - BACKGROUND: Our previous study revealed the indispensable activity of endogenous
      bone morphogenetic protein (Bmp) prior to differentiation induction of C2C12
      myoblasts for myogenesis. Here we investigated the Bmp isoform responsible for
      endogenous Bmp activity during differentiation and its role in myogenesis.
      METHODS: Gene expression of Bmp4 during myogenesis was evaluated in C2C12 cells.
      Effects of inhibition of the Bmp pathway on myogenesis were examined. Cells
      expressing Bmp4 and regulation of Bmp4 expression in myoblasts were explored.
      RESULTS: The expression of Bmp4 increased with the progression of myogenesis,
      although the extent of the increase after differentiation induction was smaller
      than that before the induction. Down-regulation of Bmp signal components
      including Bmp4, Bmpr2, and Alk2/3 inhibited the emergence of positive cells for
      myosin heavy chain II. The treatments also decreased the Myogenin expression.
      Treatment with cytosine arabinoside decreased the expression of Bmp4. Also, Bmp4
      expression was also lower in isolated myotubes than in residual cells. Expression
      of Rgm c was higher in the myotube fraction. Transcription of Bmp4 was repressed
      by the conditioned medium of mixed cells consisting of myoblasts and myotubes.
      CONCLUSION: Bmp4 expressed in myoblasts has a positive role in myotube
      formation/maturation through myogenin expression. The presence of myotubes
      inhibits Bmp4 expression in proliferating myoblasts through transcriptional
      regulation, although the expression is intrinsically increased with time of
      culture. GENERAL SIGNIFICANCE: Taken previous results on involvement of Bmp in
      the commitment of osteoblasts and adipocytes with the present results together,
      Bmp may act as a general promoter of mesenchymal cell differentiation.

PMID- 21964442
TI  - Using continuous process improvement methodology to standardize nursing handoff
      communication.
AB  - The purpose of this article was to describe the use of continuous performance
      improvement (CPI) methodology to standardize nurse shift-to-shift handoff
      communication. The goals of the process were to standardize the content and
      process of shift handoff, improve patient safety, increase patient and family
      involvement in the handoff process, and decrease end-of-shift overtime. This
      article will describe process changes made over a 4-year period as result of
      application of the plan-do-check-act procedure, which is an integral part of the
      CPI methodology, and discuss further work needed to continue to refine this
      critical nursing care process.

PMID- 21964443
TI  - Solubilization of inclusion body proteins using n-propanol and its refolding into
      bioactive form.
AB  - Inclusion bodies of recombinant human growth hormone (r-hGH) were isolated from
      Escherichia coli, enriched and solubilized in 100mM Tris buffer containing 6M n
      propanol and 2M urea. Around 4 mg/ml of r-hGH from inclusion bodies were
      solubilized in 6M n-propanol-based buffer containing 2M urea. Existence of native
      like secondary structure of r-hGH in 6M n-propanol solution was confirmed by CD
      and fluorescence spectra. Solubilized r-hGH was subsequently refolded by
      pulsatile dilution, purified to homogeneity and found to be functionally active.
      Tris buffer containing 6M n-propanol and 2M urea also effectively solubilized a
      number of proteins expressed as inclusion bodies in E. coli. Mild solubilization
      of inclusion body proteins, chaotropic effect of n-propanol at high concentration
      and kosmotropic effect at lower concentration helped in improved refolding of the
      solubilized protein. Around 40% of the r-hGH in the form of inclusion body
      aggregates was refolded into bioactive form while using n-propanol as
      solubilization agent. Solubilization with 6M n-propanol solution thus can be a
      viable alternative for achieving high throughput recovery of bioactive protein
      from inclusion bodies of E. coli.

PMID- 21964444
TI  - Expression, purification, and functional characterization of a stable helicase
      domain from a tomato mosaic virus replication protein.
AB  - Tomato mosaic virus (genus, Tobamovirus) is a member of the alphavirus-like
      superfamily of positive-strand RNA viruses, which include many plant and animal
      viruses of agronomical and clinical importance. The RNA of alphavirus-like
      superfamily members encodes replication-associated proteins that contain a
      putative superfamily 1 helicase domain. To date, a viral three-dimensional
      superfamily 1 helicase structure has not been solved. For the study reported
      herein, we expressed tomato mosaic virus replication proteins that contain the
      putative helicase domain and additional upstream N-terminal residues in
      Escherichia coli. We found that an additional 155 residues upstream of the N
      terminus of the helicase domain were necessary for stability. We developed an
      efficient procedure for the expression and purification of this fragment and have
      examined factors that affect its stability. Finally, we also showed that the
      stable fragment has nucleoside 5'-triphosphatase activity.

PMID- 21964445
TI  - Oxidative changes of lipids monitored by MALDI MS.
AB  - Oxidation processes of lipids are of paramount interest from many viewpoints. For
      instance, oxidation processes are highly important under in vivo conditions
      because molecules with regulatory functions are generated by oxidation of lipids
      or free fatty acids. Additionally, many inflammatory diseases are accompanied by
      lipid oxidation and, therefore, oxidation products are also useful disease
      (bio)markers. Thus, there is also considerable interest in methods of (oxidized)
      lipid analysis. Nowadays, soft ionization mass spectrometric (MS) methods are
      regularly used to study oxidative lipid modifications due to their high
      sensitivities and the extreme mass resolution. Although electrospray ionization
      (ESI) MS is so far most popular, applications of matrix-assisted laser desorption
      and ionization (MALDI) MS are increasing. This review aims to summarize the so
      far available data on MALDI analyses of oxidized lipids. In addition to model
      systems, special attention will be paid to the monitoring of oxidized lipids
      under in vivo conditions, particularly the oxidation of (human) lipoproteins. It
      is not the aim of this review to praise MALDI as the "best" method but to provide
      a critical survey of the advantages and drawbacks of this method.

PMID- 21964446
TI  - Structural transition in micelles: novel insight into microenvironmental changes
      in polarity and dynamics.
AB  - Structural transitions involving shape changes play an important role in cellular
      physiology. Such transition can be conveniently induced in charged micelles by
      increasing ionic strength of the medium. Shape changes have recently been shown
      to result in altered packing and lowering of micellar polarity. As a consequence
      of reduced polarity, the ionization states of micelle-bound molecules vary in
      micelles of different shape. The changes in micellar organization and dynamics
      due to structural transition can be effectively monitored utilizing the red edge
      excitation shift (REES). These changes are influenced by the position (location)
      of the probe in the micelle, i.e., the region of the micelle being monitored.
      Changes in organization and dynamics of probes and peptides upon structural
      transition are discussed with representative examples. We envisage that the
      reduction in micellar polarity and tighter packing upon structural transition
      represent important factors in the incorporation of drugs in micelles (nano
      carriers), since micellar polarity plays a crucial role in the incorporation of
      drugs.

PMID- 21964447
TI  - Quantum mechanical study of the proton exchange in the ortho-para H2 conversion
      reaction at low temperature.
AB  - Ortho-para H(2) conversion reactions mediated by the exchange of a H(+) proton
      have been investigated at very low energy for the first time by means of a time
      independent quantum mechanical (TIQM) approach. State-to-state probabilities and
      cross sections for H(+) + H(2) (v = 0, j = 0,1) processes have been calculated
      for a collision energy, E(c), ranging between 10(-6) eV and 0.1 eV. Differential
      cross sections (DCSs) for H(+) + H(2) (v = 0, j = 1) -> H(+) + H(2) (v' = 0, j' =
      0) for very low energies only start to develop a proper global minimum around the
      sideways scattering direction (theta~ 90 degrees ) at E(c) = 10(-3) eV. Rate
      coefficients, a crucial information required for astrophysical models, are
      provided between 10 K and 100 K. The relaxation ortho-para process j = 1 -> j' =
      0 is found to be more efficient than the j = 0 -> j' = 1 conversion at low
      temperatures, in line with the extremely small ratio between the ortho and para
      species of molecular hydrogen predicted at the temperature of interstellar cold
      molecular clouds. The results obtained by means of a statistical quantum
      mechanical (SQM) model, which has previously proved to provide an adequate
      description of the dynamics of the title reactions at a higher collision energy
      regime, have been compared with the TIQM results. A reasonable good agreement has
      been found with the only exception of the DCSs for the H(+) + H(2) (v = 0, j = 1)
      -> H(+) + H(2) (v' = 0, j' = 0) process at very low energy. SQM cross sections
      are also slightly below the quantum results. Estimates for the rate coefficients,
      in good accord with the TIQM values, are a clear improvement with respect to
      pioneering statistical studies on the reaction.

PMID- 21964448
TI  - Determinants of quality of life in people with epilepsy and their gender
      differences.
AB  - Improving the patient's quality of life (QOL) is the most important goal of
      epilepsy management. We performed this study to determine the factors associated
      with QOL in people with epilepsy and to assess whether there are gender
      differences in these determinants. Patients were interviewed using the Quality of
      Life in Epilepsy Inventory-31(QOLIE-31), the Adverse Event Profile (AEP), the
      Self-Rating Anxiety Scale (SAS), and the Hamilton Depression Rating Scale (HAMD).
      Two hundred forty-seven patients (152 men, 95 women) were included in the
      analysis. Among all patients, regressive analyses showed that AEP score was the
      strongest predictor of the QOLIE-31 overall score, accounting for 10.4% of the
      variance. The next strongest predictors were the number of currently used
      antiepileptic drugs (AEDs) (3.6%), the HAMD score (2.5%), and the SAS score
      (1.2%). Importantly, there were gender differences in these predictors of QOL.
      The strongest predictors of the QOLIE-31 overall score in women were the AEP
      score and the number of AEDs. In contrast, the strongest predictors in men were
      the SAS score, the AEP score and the frequency of seizures. These results
      indicate that perceived adverse effects of treatments and number of AEDs exerted
      greater effects on QOL in women, whereas anxiety and seizure-related variables
      had a stronger impact on QOL among men. Accordingly, it may be necessary to
      individualize interventions to improve the QOL of people with epilepsy.

PMID- 21964449
TI  - A programmable triangular neighborhood function for a Kohonen self-organizing map
      implemented on chip.
AB  - An efficient transistor level implementation of a flexible, programmable
      triangular function (TF) that can be used as a triangular neighborhood function
      (TNF) in ultra-low power, self-organizing maps (SOMs) realized as application
      specific integrated circuit (ASIC) is presented. The proposed TNF block is a
      component of a larger neighborhood mechanism, whose role is to determine the
      distance between the winning neuron and all neighboring neurons. Detailed
      simulations carried out for the software model of such network show that the TNF
      forms a good approximation of the gaussian neighborhood function (GNF), while
      being implemented in a much easier way in hardware. The overall mechanism is very
      fast. In the CMOS 0.18 MUm technology, distances to all neighboring neurons are
      determined in parallel, within the time not exceeding 11 ns, for an example
      neighborhood range, R, of 15. The TNF blocks in particular neurons require
      another 6 ns to calculate the output values directly used in the adaptation
      process. This is also performed in parallel in all neurons. As a result, after
      determining the winning neuron, the entire map is ready for the adaptation after
      the time not exceeding 17 ns, even for large numbers of neurons. This feature
      allows for the realization of ultra low power SOMs, which are hundred times
      faster than similar SOMs realized on PC. The signal resolution at the output of
      the TNF block has a dominant impact on the overall energy consumption as well as
      the silicon area. Detailed system level simulations of the SOM show that even for
      low resolutions of 3 to 6 bits, the learning abilities of the SOM are not
      affected. The circuit performance has been verified by means of transistor level
      Hspice simulations carried out for different transistor models and different
      values of supply voltage and the environment temperature - a typical procedure
      completed in case of commercial chips that makes the obtained results reliable.

PMID- 21964450
TI  - Posterior surgical correction of posttraumatic kyphosis of the thoracolumbar
      segment.
AB  - OBJECTIVES: To analyze the clinical characteristics and surgical results of
      posttraumatic kyphosis of the thoracolumbar segment. METHODS: Thirty-four
      patients with posttraumatic kyphosis of the thoracolumbar segment underwent
      posterior osteotomy, kyphosis correction, and fixation at our hospital. The
      kyphosis apex was from T10 to L2. There were 15 male and 19 female patients. The
      mean age was 48.9 years. Full-spine standing radiographs were obtained before
      surgery, after surgery, and at follow-up. The sagittal spine balance status was
      evaluated, and the kyphotic angle, the lumbar lordotic angle, and the thoracic
      kyphotic angle were measured. The Frankel grading system for neurological
      functions and the Visual Analogue Scale for back pain were evaluated before
      surgery and at follow-up. The Oswestry Disability Index was applied for
      assessment of life quality and surgical results of patients. The Patient
      Satisfied Index (PSI) was also used for determination of surgical results.
      Patients were grouped according to the extent of kyphotic angle and the surgical
      technique. The difference in kyphosis correction and back pain between groups was
      observed before and after surgery. Relief from neurological symptoms was also
      observed. RESULTS: The average kyphotic angle was 48.5 degrees, the average
      lumbar lordotic angle was 57.9 degrees, and the average thoracic kyphotic angle
      was 11.4 degrees before surgery. The sagittal spine balance was well maintained
      in 14 cases, and negative imbalance and positive imbalance were seen in 13 cases
      and 7 cases, respectively. There was significant difference in back pain between
      patients in the abnormal and normal groups of the lumbar lordotic angle. The
      average follow-up time after surgery was 32.1 months. The average kyphotic angle
      correction rate was 90.4% after surgery and 87.2% at follow-up. The average
      Oswestry Disability Index was 50.4% before surgery, which improved to 29.4% at
      follow-up, with an improvement rate of 41.5%. The Patient Satisfied Index result
      showed a total satisfactory rate of 94.1%. There were 16 cases of neurological
      deficit before surgery; 8 of them achieved various degrees of improvement after
      surgery. CONCLUSIONS: Surgical correction of posttraumatic kyphosis of the
      thoracolumbar segment can show good radiologic and clinical results with the
      appropriate procedure according to the extent of the kyphosis angle. Some
      patients with neurological deficit are still worthy of surgical treatment.

PMID- 21964451
TI  - Polyetheretherketone interbody cages versus autogenous iliac crest bone grafts
      with anterior fixation for cervical disc disease.
AB  - OBJECTIVE: The aim of this study was to compare the fusion rate, operation time,
      recovery of disc space height, clinical duration and improvement, return to
      activities of daily living, and complication rate associated with anterior
      cervical discectomy with interbody fusion by using polyetheretherketone cages or
      autogenous iliac crest bone grafts as disc replacement in a series of 60
      patients. MATERIALS AND METHODS: Between November 2006 and February 2010 a
      retrospective analytical observational cohort study was carried out in 60
      consecutive patients surgically treated with anterior cervical discectomy with
      interbody fusion for degenerative disc desease at the Neurosurgical Department of
      the Hospital Italiano de Buenos Aires. The patients were divided into 2 groups
      for the assessment of clinical characteristics, demographics, fusion rates,
      duration of surgical procedure, neurological and functional outcomes, imaging
      results, and complications. Group A included patients treated with autogenous
      iliac crest bone grafts, and group B included patients treated with
      polyetheretherketone cages. RESULTS: The mean age of the patients was 50.8 years.
      Female patients comprised the majority in both groups (63.3%). Cervicobrachialgia
      was the most common presentation. Clinical improvement, fusion rates, and
      recovery of disc space height were similar in both groups. The operation time was
      significantly shorter in the polyetheretherketone group (P<0.001). Twenty percent
      (n=6) of the patients in group A suffered complications, >80% of which were
      associated with iliac crest bone graft harvesting. Patients in group B had no
      complications (P<0.05). CONCLUSIONS: Although outcomes were very successful in
      both groups in terms of fixation stability, recovery of disc space, return to
      activities of daily living and work, and remission of symptoms, operation time
      was considerably shorter for patients in the polyetheretherketone group, who had
      none of the complications associated with iliac crest bone graft harvesting, both
      differences being statistically significant.

PMID- 21964452
TI  - Hemostasis with a bipolar sealer during surgical correction of adolescent
      idiopathic scoliosis.
AB  - STUDY DESIGN: Retrospective before-after comparison study. OBJECTIVE: The primary
      aim of this study was to evaluate the effectiveness of a radiofrequency-based
      bipolar hemostatic sealer during surgical correction of adolescent idiopathic
      scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Spinal reconstructive surgery is
      commonly associated with excessive blood loss. Perioperative bleeding is of
      particular concern during correction of AIS, which often requires allogeneic or
      autologous transfusion. However, there are specific risks and limitations that
      often preclude the utilization of transfusions. Alternatives include the use of
      antifibrinolytic drugs and topical fibrin-based and thrombin-based agents,
      although safety and effectiveness are yet to be fully established. There is a
      clear need for assessing alternative methods of hemostasis. METHODS: One hundred
      seventy-six AIS patients undergoing corrective spinal surgery were included in
      this study. Seventy-six consecutive patients were treated intraoperatively with a
      standard method of hemostasis consisting of hypotensive anesthesia, thrombin
      soaked sponges, and intraoperative blood salvage (Control). Subsequently, an
      additional 100 consecutive patients were treated after the introduction of a
      bipolar sealer (Aquamantys 2.3 Bipolar Sealer, Salient Surgical Technologies,
      Portsmouth, NH). The outcomes of this study were estimated blood loss (total and
      per level) and transfusion rate. RESULTS: Blood loss was reduced by 57% after the
      introduction of the bipolar sealer compared with the Control (bipolar sealer:
      435+/-192 mL, Control: 1009+/-392 mL; P<0.001). There was a statistically
      significant difference between groups for blood loss per fusion level (bipolar
      sealer: 39+/-17 mL, Control: 95+/-33 mL; P<0.001). Five (6.6%) Control patients
      required blood transfusions versus none treated with the bipolar sealer
      (P=0.014). Complication rates were similar between the groups. CONCLUSIONS: These
      findings suggest that the Aquamantys 2.3 bipolar sealer effectively supports
      hemostasis and reduces the need for transfusions during surgical correction of
      AIS.

PMID- 21964453
TI  - Axial presacral lumbar interbody fusion and percutaneous posterior fixation for
      stabilization of lumbosacral isthmic spondylolisthesis.
AB  - STUDY DESIGN: Case series. OBJECTIVE: To describe a minimally invasive surgical
      technique for treatment of lumbosacral spondylolisthesis. SUMMARY OF BACKGROUND
      DATA: Traditional surgical management of lumbosacral spondylolisthesis is
      technically challenging and associated with significant complications. Minimally
      invasive surgical techniques offer patients treatment alternatives with lower
      operative morbidity risk. The combination of percutaneous pedicle screw reduction
      and an axial presacral approach for lumbosacral discectomy and fusion is an
      option for the surgical management of low-grade lumbosacral spondylolisthesis.
      METHODS: Twenty-six consecutive patients with symptomatic L5-S1 level isthmic
      spondylolisthesis (grade 1 or grade 2) underwent axial presacral lumbar interbody
      fusion and percutaneous posterior fixation. Study outcomes included visual
      analogue scale for axial pain severity, Odom criteria, and radiographic fusion.
      RESULTS: The procedure was successfully completed in all patients with no
      intraoperative complications reported. Intraoperative blood loss was minimal
      (range, 20-150 mL). Median hospital stay was 1 day (range, <1-2 d).
      Spondylolisthesis grade was improved after axial lumbar interbody fusion
      (P<0.001) with 50% (13 of 26) of patients showing a reduction of at least 1
      grade. Axial pain severity improved from 8.1+/-1.4 at baseline to 2.8+/-2.3 after
      axial lumbar interbody fusion, representing a 66% reduction from baseline (95%
      confidence interval, 54.3%-77.9%). At 2-year posttreatment, all patients showed
      solid fusion. Using Odom criteria, 81% of patients were judged as excellent or
      good (16 excellent, 5 good, 3 fair, and 2 poor). There were no perioperative
      procedure-related complications including infection or bowel perforation. During
      postoperative follow-up, 4 patients required reintervention due to recurrent
      radicular (n=2) or screw-related (n=2) pain. CONCLUSIONS: The minimally invasive
      presacral axial interbody fusion and posterior instrumentation technique is a
      safe and effective treatment for low-grade isthmic spondylolisthesis.

PMID- 21964454
TI  - Reversal of anterior cervical discectomy and fusion with cervical artificial disc
      replacement: regain motion after 9 years fusion.
AB  - STUDY DESIGN: Case report and review of the literature. OBJECTIVE: To present a
      conversion of an anterior cervical discectomy and fusion (ACDF) with a cervical
      artificial disc replacement in a 39-year-old woman and to review the relevant
      literature. SUMMARY OF BACKGROUND DATA: Return of functional spinal unit motion 9
      years after attempted fusion is extremely rare. METHODS: The patient underwent an
      attempted anterior cervical discectomy and fusion 9 years earlier for bilateral
      hand numbness and leg weakness. Most of her neurological deficits had resolved
      after the index operation, but returned 2 months before the second operation and
      were unresponsive to nonoperative treatment. Computed tomography (CT) myelography
      showed recurrence of cervical disc herniation at the cephalad adjacent segment,
      which compressed the spinal cord. There was still some osteophyte at the C5/6
      level that was also causing compression to the spinal cord. A solid fusion was
      suspected at this level. Surgery was performed to take down the grafted region
      and replace both levels with artificial disks. RESULTS: The range of motion (ROM)
      of the revised level at the 6-month follow-up was well preserved, there was no
      sign of instability at either operated level. The 6-month follow-up CT scan shows
      that, there was no obvious compression in the spinal canal. The remobilized facet
      joints of C5/6 segment have not demonstrated further degeneration. The patient's
      neck symptom and neurological function were significantly recovered. CONCLUSIONS:
      This case demonstrates application of a cervical artificial disc replacement to
      restore motion at a level that was previously grafted and fused. In select cases,
      cervical artificial disc replacement may represent a reasonable alternative to a
      repeated attempt at fusion. It is imperative that preoperatively lack of fusion
      of the facet joints be demonstrated on reconstructed CT scanning.

PMID- 21964455
TI  - A cadaver study to compare vertebral augmentation with a high-viscosity cement to
      augmentation with conventional lower-viscosity cement.
AB  - STUDY DESIGN: Comparison of extravasations in fractured cadaver vertebrae
      augmented with commercial low-viscosity versus high-viscosity cements. OBJECTIVE:
      Use of high-resolution, 3-dimensional (3D) imaging to test the hypothesis that
      high-viscosity cements can reduce the type and severity of extravasations after
      vertebral augmentation procedures. SUMMARY OF BACKGROUND DATA: Cement
      extravasations are one of the primary complications of vertebral augmentation
      procedures. There is some evidence that high-viscosity cements might reduce
      extravasations, but additional data are needed to confirm the early findings.
      METHODS: A range of vertebral fractures were created in fresh human cadavers. One
      group was then augmented with a low-viscosity polymethylmethacrylate (PMMA)-based
      cement and the other group injected with high-viscosity PMMA-based cement. High
      resolution computerized tomography exams were obtained, and extravasations were
      assessed using 3D volume renderings. The type and severity of extravasations were
      recorded and analyzed. RESULTS: The proportion of vertebrae with any type of
      extravasation through the posterior wall to the spinal canal, into small vessels
      laterally or anteriorly, through the endplates, or anywhere around the body was
      not significantly different between the high-viscosity and low-viscosity groups.
      There was significantly less severe extravasation through the endplates (P=0.02),
      and a trend toward less severe extravasation through vessels (P=0.06) with the
      high versus low-viscosity cements. CONCLUSIONS: In agreement with previous
      research, high-viscosity PMMA-based cement may help to reduce the more severe
      forms of extravasations after vertebral augmentation procedures in newly
      fractured vertebrae.

PMID- 21964456
TI  - A novel in vivo inducible expression system in Edwardsiella tarda for potential
      application in bacterial polyvalence vaccine.
AB  - Recombinant bacterial vector vaccine is an attractive vaccination strategy to
      induce the immune response to a carried protective antigen, and the main concern
      of bacterial vector vaccine is to establish a stable antigen expression system in
      vector bacteria. Edwardsiella tarda is an important facultative intracellular
      pathogen of both animals and humans, and its attenuated derivates are excellent
      bacterial vectors for use in recombinant vaccine design. In this study, we design
      an in vivo inducible expression system in E. tarda and establish potential
      recombinant E. tarda vector vaccines. With wild type strain E. tarda EIB202 as a
      vector, 53 different bacteria-originated promoters were examined for iron
      responsive transcription in vitro, and the promoters P(dps) and P(yncE) showed
      high transcription activity. The transcription profiles in vivo of two promoters
      were further assayed, and P(dps) revealed an enhanced in vivo inducible
      transcription in macrophage, larvae and adult zebra fish. The gapA34 gene,
      encoding the protective antigen GAPDH from the fish pathogen Aeromonas hydrophila
      LSA34, was introduced into the P(dps)-based protein expression system, and
      transformed into attenuated E. tarda strains. The resultant recombinant vector
      vaccine WED/pUTDgap was evaluated in turbot (Scophtalmus maximus). Over 60% of
      the vaccinated fish survived under the challenge with A. hydrophila LSA34 and E.
      tarda EIB202, suggesting that the P(dps)-based antigen delivery system had great
      potential in bacterial vector vaccine application.

PMID- 21964457
TI  - Rapporteur's report on session 5: Risk management & prevention.

PMID- 21964458
TI  - Metabolic regulation of the squid nerve Na+/Ca2+ exchanger: recent kinetic,
      biochemical and structural developments.
AB  - The Na+/Ca2+ exchangers are structural membrane proteins, essential for the
      extrusion of Ca2+ from most animal cells. Apart from the transport sites, they
      have several interacting ionic and metabolic sites located at the intracellular
      loop of the exchanger protein. One of these, the intracellular Ca2+ regulatory
      sites, are essential and must be occupied by Ca2+ to allow any type of ion (Na+
      or Ca2+) translocation. Intracellular protons and Na+ are inhibitory by reducing
      the affinity of the regulatory sites for Ca2+; MgATP stimulates by antagonizing
      H+ and Na+. We have proposed a kinetic scheme to explain all ionic and metabolic
      regulation of the squid nerve Na+/Ca2+ exchanger. This model uniquely accounts
      for most of the new kinetic data provided here; however, none of the existing
      models can explain the trans effects of the Ca(i)2+-regulatory sites on external
      cation transport sites; i.e. all models are incomplete. MgATP up-regulation of
      the squid Na+/Ca2+ exchanger requires a cytosolic protein, which has been
      recently identified as a member of the lipocalin super family of Lipid Binding
      Proteins (LBP or FABP) of 132 amino acids (ReP1-NCXSQ, access to GenBank
      EU981897). This protein was cloned, expressed and purified. To be active, ReP1
      NCXSQ must be phosphorylated from MgATP by a kinase present in the plasma
      membrane. Phosphorylated ReP1-NCXSQ can stimulate the exchanger in the absence of
      ATP. Experiments with proteoliposomes proved that this up-regulation can take
      place just with the lipid membrane and the exchanger protein. The structure of
      ReP1-NCXSQ predicted from the amino acid sequence has been confirmed by X-ray
      crystal analysis; it has a "barrel" formed by ten beta sheets and two alpha
      helices, with a lipid coordinated by hydrogen bonds with Arg 126 and Tyr 128.

PMID- 21964459
TI  - Structural basis for cytokinin recognition by Arabidopsis thaliana histidine
      kinase 4.
AB  - Cytokinins are classic hormones that orchestrate plant growth and development and
      the integrity of stem cell populations. Cytokinin receptors are eukaryotic sensor
      histidine kinases that are activated by both naturally occurring adenine-type
      cytokinins and urea-based synthetic compounds. Crystal structures of the
      Arabidopsis thaliana histidine kinase 4 sensor domain in complex with different
      cytokinin ligands now rationalize the hormone-binding specificity of the receptor
      and may spur the design of new cytokinin ligands.

PMID- 21964460
TI  - All-trans retinoic acid protects against arsenic-induced uterine toxicity in
      female Sprague-Dawley rats.
AB  - BACKGROUND AND PURPOSE: Arsenic exposure frequently leads to reproductive
      failures by disrupting the rat uterine histology, hormonal integrity and estrogen
      signaling components of the rat uterus, possibly by generating reactive oxygen
      species. All-trans retinoic acid (ATRA) was assessed as a prospective therapeutic
      agent for reversing reproductive disorders. EXPERIMENTAL APPROACH: Rats exposed
      to arsenic for 28 days were allowed to either recover naturally or were treated
      simultaneously with ATRA for 28 days or treatment continued up to 56 days.
      Hematoxylin-eosin double staining was used to evaluate changes in the uterine
      histology. Serum gonadotropins and estradiol were assayed by ELISA. Expression of
      the estrogen receptor (ERalpha), an estrogen responsive gene vascular endothelial
      growth factor (VEGF), and cell cycle regulatory proteins, cyclin D1 and CDK4, was
      assessed by RT-PCR, immunohistochemistry and western blot analysis. KEY RESULTS:
      ATRA ameliorated sodium arsenite-induced decrease in circulating estradiol and
      gonadotropin levels in a dose- and time-dependent manner, along with recovery of
      luminal epithelial cells and endometrial glands. Concomitant up regulation of
      ERalpha, VEGF, cyclin D1, CDK4 and Ki-67 was also observed to be more prominent
      for ATRA-treated rats as compared to the rats that were allowed to recover
      naturally for 56 days. CONCLUSIONS AND IMPLICATIONS: Collectively, the results
      reveal that ATRA reverses arsenic-induced disruption of the circulating levels of
      gonadotropins and estradiol, and degeneration of luminal epithelial cells and
      endometrial glands of the rat uterus, indicating resumption of their functional
      status. Since structural and functional maintenance of the pubertal uterus is
      under the influence of estradiol, ATRA consequently up regulated the estrogen
      receptor and resumed cellular proliferation, possibly by an antioxidant
      therapeutic approach against arsenic toxicity.

PMID- 21964461
TI  - Role of training activities for the reduction of pre-analytical errors in
      laboratory samples from primary care.
AB  - BACKGROUND: The presence of pre-analytical errors (PE) is a usual contingency in
      laboratories. The incidence may increase where it is difficult to control that
      period, as it is the case with samples sent from primary care (PC) to clinical
      reference laboratory. Detection of a large number of PE in PC samples in our
      Institution led to the development and implementation of preventive strategies.
      The first of these has been the realization of a cycle of educational sessions
      for PC nurses, followed by the evaluation of their impact on PE number. METHODS:
      The incidence of PE was assessed in two periods, before (October-November 2007)
      and after (October-November, 2009) the implementation of educational sessions.
      Eleven PC centers in the urban area and 17 in the rural area participated. In the
      urban area, samples were withdrawn by any PC nurse; in the rural area, samples
      were obtained by the patient's reference nurse. The types of analyzed PE included
      missed sample (MS), hemolyzed sample (HS), coagulated sample (CS), incorrect
      sample (ISV) and others (OPE), such as lipemic or icteric serum or plasma.
      RESULTS: In the former period, we received 52,669 blood samples and 18,852 urine
      samples, detecting 3885 (7.5%) and 1567 (8.3%) PEs, respectively. After the
      educational intervention, there were 52,659 and 19,048 samples with 5057 (9.6%)
      and 1.256 (6.5%) PEs, respectively (p<0.001). According to the type of PE, the
      incidents compared before and after compared incidences were: MS, 4.8% vs. 3.8%,
      p<0.001; HS, 1.97% vs. 3.9%, p<0.001; CS, 0.54% vs. 0.25%, p<0.001; ISV, 0.15%
      vs. 0.19% p=0.08; and OPE, 0.3% vs. 0.42%, p<0.001. CONCLUSIONS: Surprisingly the
      PE incidence increased after the educational intervention, although it should be
      noted that it was primarily due to the increase of HS, as the other EP incidence
      decreased (MS and CS) or remained unchanged (ISV). This seems to indicate the
      need for a comprehensive approach to reduce the incidence of errors in the pre
      analytical period, as one stage interventions do not seem to be effective enough.

PMID- 21964462
TI  - Multiple feedback loops achieve robust localization of wingless expression in
      Drosophila notum development.
AB  - Organ morphogenesis starts with the spatial patterning of different gene
      expressions in organ primordia, which is based on positional information provided
      by morphogens. To generate precise positional information, the robust
      localization of morphogen sources is needed. This can be realized by several
      different mechanisms, such as (i) by reducing the variations in spatial
      arrangement of morphogen sources, (ii) by reducing the variations in their source
      levels, and (iii) by increasing the degree of source localization with the sharp
      boundary that makes morphogen gradients steeper. Here we focus on the mechanism
      of localization of wingless expression, one of the important morphogens in
      Drosophila notum development. The mechanism of wingless-localization can be
      explained by a simple feed-forward loop network motif, but the real molecular
      network adopted by the organism is much more complex; it includes multiple
      feedback loops that function with the feed-forward loop in a coordinated manner.
      To clarify the functions of the molecular network, we decompose it into three sub
      modules, each of which includes a single feedback loop, and examine their
      possible roles using a mathematical model. We demonstrate how the regulatory
      network for wingless expression realizes the conditions (i)-(iii) for its robust
      localization.

PMID- 21964464
TI  - Regulation of activin and inhibin in the adult testis and the evidence for
      functional roles in spermatogenesis and immunoregulation.
AB  - Activin A provides a unique link between reproduction and immunity, which is
      especially significant in the adult testis. This cytokine, together with inhibin
      B and follistatin acting as regulators of activin A activity, is fundamentally
      involved in the regulation of spermatogenesis and testicular steroidogenesis.
      However, activin A also has a much broader role in control of inflammation,
      fibrosis and immunity. In the Sertoli cell, activin A is regulated by signalling
      pathways that normally regulate stress and inflammation, signalling pathways that
      intersect with the classical hormonal regulatory pathways mediated by FSH.
      Modulation of activin A production and activity during spermatogenesis is
      implicated in the fine control of the cycle of the seminiferous epithelium. The
      immunoregulatory properties of activin A also suggest that it may be involved in
      maintaining testicular immune privilege. Consequently, elevated activin A
      production within the testis during inflammation and infection may contribute to
      spermatogenic failure, fibrosis and testicular damage.

PMID- 21964465
TI  - Activation of estrogen receptor alpha by raloxifene through an activating protein
      1-dependent tethering mechanism in human cervical epithelial cancer cells: a role
      for c-Jun N-terminal kinase.
AB  - Nuclear estrogen receptor alpha (ERalpha) regulates target gene expression in
      response to ligands through two distinct mechanisms: direct binding to DNA and
      indirect tethering through other DNA-bound transcription factors, such as AP-1.
      In the studies described herein, we examined the molecular mechanisms underlying
      the activation of ERalpha in the AP-1 tethering pathway by the selective estrogen
      receptor modulator (SERM) raloxifene (Ral). Our results with the MMP1 and PRUNE
      genes indicate that the c-Fos component of the AP-1 tethering factor and the c
      Jun N-terminal kinase 1 (JNK1) are constitutively bound at the promoter regions
      prior to Ral exposure. Ral then promotes the binding of ERalpha at the promoter
      in a c-Fos-dependent manner. Interestingly, we found that JNK1 enzymatic activity
      is required for Ral-dependent gene activation through ERalpha. Our results
      suggest that one role for Ral-dependent recruitment of ERalpha to the AP-1
      binding site is to stimulate JNK1 enzymatic activity. Alternatively, Ral-occupied
      ERalpha might recruit protein substrates to promoter-bound JNK1 without any
      change in JNK1 activity. Collectively, our studies have revealed a new role for
      JNK1 in determining gene regulatory outcomes by ERalpha.

PMID- 21964466
TI  - From the ranks of mammary progesterone mediators, RANKL takes the spotlight.
AB  - Whether during the diestrus phase of the estrous cycle or with pregnancy onset,
      the mitogenic effects of progesterone are well-established in the murine mammary
      epithelium. Importantly, progesterone-induced mitogenicity is critical for
      mammary tumor promotion, providing one explanation for the increase in breast
      cancer-risk observed with prolonged progestin-based hormone therapy. At the
      cellular level, progesterone projects its mitogenic influence through an
      evolutionary conserved paracrine mechanism of action. In this regard, recent
      studies provide compelling support for receptor activator of NF-kB ligand (RANKL)
      as a key paracrine mediator of the progesterone mitogenic signal. Induction of
      RANKL is sufficient to elicit mammary ductal side-branching and alveologenesis,
      the very morphogenetic responses elicited by progesterone during pregnancy and at
      diestrus. Significantly, the proliferative and pro-survival signals triggered by
      RANKL are also required for progestin-promotion of mammary tumorigenesis,
      underscoring a dual role for RANKL in progesterone-dependent mammary
      morphogenesis and tumorigenesis. Recently, RANKL has been shown to be critical
      for progesterone-induced expansion of the mammary stem cell population (and its
      lineal descendents), thereby advancing our conceptual understanding not only of
      RANKL's involvement in normal mammary morphogenesis but also in breast cancer
      risk associated with sustained hormone exposure. Finally, these studies together
      suggest that chemotherapeutic intervention of RANKL signaling represents a
      feasible approach for the effective prevention and/or treatment of hormone
      responsive breast cancers.

PMID- 21964467
TI  - AcrB contamination in 2-D crystallization of membrane proteins: lessons from a
      sodium channel and a putative monovalent cation/proton antiporter.
AB  - Contamination with the multidrug transporter AcrB represents a potential pitfall
      in the structural analysis of recombinant membrane proteins expressed in
      Escherichia coli, especially when high-throughput approaches are adopted. This
      can be a particular problem in two-dimensional (2-D) crystallization for electron
      cryomicroscopy since individual crystals are too small for compositional
      analysis. Using a broad 'sparse matrix' of buffer conditions typically used in 2
      D crystallization, we have identified at least eight unique crystal forms of
      AcrB. Reference to images and projection maps of these different forms can
      greatly facilitate the early identification of false leads in 2-D crystallization
      trials of other membrane proteins of interest. We illustrate the usefulness of
      such data by highlighting two studies of membrane proteins in our laboratories.
      We show in one case (a bacterial sodium channel, NaChBac) how early
      crystallization 'hits' could be attributed to contaminating AcrB by comparison
      against our AcrB crystal image database. In a second case, involving a member of
      the monovalent cation/proton antiporter-1 family (MPSIL0171), a comparison with
      the observed AcrB crystal forms allowed easy identification of reconstituted AcrB
      particles, greatly facilitating the eventual purification and crystallization of
      the correct protein in pure form as ordered helical arrays. Our database of AcrB
      crystal images will be of general use in assisting future 2-D crystallization
      studies of other membrane proteins.

PMID- 21964468
TI  - Actin bundling and polymerisation properties of eukaryotic elongation factor 1
      alpha (eEF1A), histone H2A-H2B and lysozyme in vitro.
AB  - Elongation factor 1 alpha (eEF1A) is a positively charged protein which has been
      shown to interact with the actin cytoskeleton. However, to date, a specific actin
      binding site within the eEF1A sequence has not been identified and the mechanism
      by which eEF1A interacts with actin remains unresolved. Many protein-protein
      interactions occur as a consequence of their physicochemical properties and actin
      bundle formation has been shown to result from non-specific electrostatic
      interaction with basic proteins. This study investigated interactions between
      actin, eEF1A and two other positively charged proteins which are not regarded as
      classic actin binding proteins (namely lysozyme and H2A-H2B) in order to compare
      their actin organising effects in vitro. For the first time using atomic force
      microscopy (AFM) we have been able to image the interaction of eEF1A with actin
      and the subsequent bundling of actin in vitro. Interestingly, we found that eEF1A
      dramatically increases the rate of polymerisation (45-fold above control levels).
      We also show for the first time that H2A-H2B has remarkably similar effects upon
      actin bundling (relative bundle size/number) and polymerisation (35-fold increase
      above control levels) as eEF1a. The presence of lysozyme resulted in bundles
      which were distinct from those formed due to eEF1A and H2A-H2B. Lysozyme also
      increased the rate of actin polymerisation above the control level (by 10-fold).
      Given the striking similarities between the actin bundling and polymerisation
      properties of eEF1A and H2A-H2B, our results hint that dimerisation and
      electrostatic binding may provide clues to the mechanism through which eEF1A
      actin bundling occurs.

PMID- 21964469
TI  - CB1 receptor-deficient mice as a model for depression.
AB  - In the last 10 years, numerous experimental studies have revealed the
      participation of the endocannabinoid system in the control of emotional behavior
      and mood through the activation of the CB1 cannabinoid receptors.
      Endocannabinoids are able to exert a regulative control of different
      physiological mechanisms that are impaired during mood disorders, including
      monoaminergic system, the activity of pituitary-adrenal axis, the release and
      activation of neurotrophic factors that promotes neuroplasticity and adapted
      behavior, and probably neuroinflammatory cytokines release during the depressive
      disorders. Considering the body of elements that acts under the control of the
      endocannabinoid system and the key role played by the activation of the CB1
      cannabinoid receptors in the control of emotion and mood, we had proposed that
      genetically modified mice lacking the CB1 cannabinoid receptors could represent a
      genetic model for depression. These animals generated by three distinct
      laboratories behave normally under basal conditions, but they could display an
      altered behavior under adverse environmental conditions. In this review, we have
      integrated most of the study that have been developed using mice lacking CB1
      cannabinoid receptor for the studies of emotional responses. We have focused our
      attention not only in the data obtained using different behavioral paradigms, but
      also in different biomarkers that have been classically or recently associated to
      mood disorders, such as the deregulation of the serotonergic system, the reported
      impairment in neurotrophic factors and plasticity function described for
      depression, the alterations in the pituitary-adrenal axis function, and the
      lately reported role for inflammatory factors in the mood regulation. Finally,
      clinical studies support and confirm the obtained findings in animal models and
      lead us to propose that mice lacking CB1 cannabinoid receptor could represent a
      validate and appropriate model to evaluate depressive-like disorders in animals.

PMID- 21964470
TI  - Delayed axonal degeneration in slow Wallerian degeneration mutant mice detected
      using diffusion tensor imaging.
AB  - Previous studies have shown the feasibility of using diffusion tensor imaging
      (DTI) as a noninvasive imaging modality to evaluate neurodegeneration in humans
      and animals. The axial and radial diffusivities derived from DTI were
      demonstrated to be sensitive markers for axonal and myelin damage, respectively.
      This study used DTI to evaluate optic nerve degeneration in wild-type and slow
      Wallerian degeneration (Wld(S)) mutant mice. Longitudinal DTI was performed on
      optic nerves following high intraocular pressure-induced transient retinal
      ischemia. The axial diffusivity of wild-type nerves decreased 30% (P<0.05) at 3
      days and 40% (P<0.05) at 5-30 days after transient elevation of intraocular
      pressure. In contrast, the axial diffusivity of Wld(S) nerves did not change at 3
      days; decreased by 20% (P<0.05) at 5 days, and continued to decrease by 30%
      (P<0.05) at 15 days and 40% (P<0.05) at 30 days after transient intraocular
      pressure elevation, suggesting delayed axonal damage in Wld(S) mice. Radial
      diffusivity increased 200% (P<0.05) at 15-30 days in the wild-type mice and 100%
      (P<0.05) at 30 days in the Wld(S) mice after transient intraocular pressure
      elevation, suggesting delayed myelin damage in Wld(S) mice. DTI detected damage
      was confirmed with immunohistochemistry using phosphorylated neurofilament and
      myelin basic protein for assessing axonal and myelin integrity, respectively.
      These findings support the use of DTI not only to evaluate the progression of
      neurodegeneration but also to noninvasively demonstrate Wld(S) mutation to delay
      the Wallerian degeneration.

PMID- 21964471
TI  - Inhibitory role of diazepam on autoimmune inflammation in rats with experimental
      autoimmune encephalomyelitis.
AB  - Glutamate and GABA are the main excitatory and inhibitory neurotransmitters in
      the CNS, and both may be involved in the neuronal dysfunction in
      neurodegenerative conditions. We have recently found that glutamate release was
      decreased in isolated synaptosomes from the rat cerebral cortex during the
      development of experimental autoimmune encephalomyelitis (EAE), the animal model
      of multiple sclerosis. In contrast to control animals where GABA induced a
      decrease in the evoked glutamate release, which was abolished by picrotoxin (a
      GABA(A) antagonist), synaptosomes from EAE rats showed a loss in the inhibition
      of the glutamate release mediated by GABA with a concomitant diminution of the
      flunitrazepam-sensitive GABA(A) receptor density. We have presently further
      evaluated the relevance of the GABAergic system in EAE by treating rats
      challenged for the disease with the GABA agonist diazepam. Administration of
      diazepam during 6 days starting at day 6 or 11 after EAE active induction led to
      a marked decrease of the disease incidence and histological signs associated with
      the disease. Cellular reactivity and antibody responses against the
      encephalitogenic myelin basic protein were also diminished. Beyond the effects of
      diazepam on the autoimmune, inflammatory response, we report also a positive
      effect on neurotransmission. Treatment with diazepam inhibited the previously
      described reduction in glutamate release in the frontal cortex synaptosomes from
      EAE animals. These data suggest that an endogenous inhibitory GABAergic system
      within the immune system is involved in the diazepam effect on EAE and indicate
      that increasing GABAergic activity potently ameliorates EAE.

PMID- 21964472
TI  - Grey matter volume correlates with virtual water maze task performance in boys
      with androgen excess.
AB  - Major questions remain about the specific role of testosterone in human spatial
      navigation. We tested 10 boys (mean age 11.65 years) with an extremely rare
      disorder of androgen excess (Familial Male Precocious Puberty, FMPP) and 40
      healthy boys (mean age 12.81 years) on a virtual version of the Morris Water Maze
      task. In addition, anatomical magnetic resonance images were collected for all
      patients and a subsample of the controls (n=21) after task completion.
      Behaviourally, no significant differences were found between both groups.
      However, in the MRI analyses, grey matter volume (GMV) was correlated with
      performance using voxel-based morphometry (VBM). Group differences in
      correlations of performance with GMV were apparent in medial regions of the
      prefrontal cortex as well as the middle occipital gyrus and the cuneus. By
      comparison, similar correlations for both groups were found in the inferior
      parietal lobule. These data provide novel insight into the relation between
      testosterone and brain development and suggest that morphological differences in
      a spatial navigation network covary with performance in spatial ability.

PMID- 21964473
TI  - TC10beta/CDC42 GTPase activating protein is required for the growth of cortical
      neuron dendrites.
AB  - Neuronal morphogenesis plays an important role in neuronal development.
      TC10beta/CDC42 GTPase-activating protein (TCGAP) is known to be a brain-enriched
      multiple domain protein, but its role in neuronal development process remains
      poorly understood. In the present study, we showed that TCGAP positively
      regulated dendritic outgrowth and spine formation in developing cortical neurons.
      Knocking down TCGAP by RNA interference led to a decrease in the overall length
      of dendrite arbors and the number of dendrite branches both in vitro and in vivo.
      Overexpressing TCGAP in cultured cortical neurons increased dendritic outgrowth
      and branching. Moreover, overexpressing TCGAP lead to an increase of spine
      density while knocking-down TCGAP decreased spine density in vivo. The defect by
      downregulating TCGAP could be rescued by expressing a knock-down resistant form
      of TCGAP both in vivo and in vitro. In contrast, neither downregulating nor
      overexpressing TCGAP had any effect on axonal morphogenesis in primary cortical
      neuron cultures. Together, our findings suggest that TCGAP regulates neuronal
      morphogenesis in developing cortical neurons at both early and late stage.

PMID- 21964474
TI  - In vitro toxicity assessment of three hydroxylated fullerenes in human skin
      cells.
AB  - Carbon fullerenes possess unique properties and their interactions with
      biomolecules have widespread applications. Functionalization of fullerenes with
      hydroxyl groups (fullerenols) can increase the solubility and potential for
      cellular interaction, but the health and safety effects of varying degrees of
      fullerene hydroxylation in biological systems is poorly understood. Existing
      reports regarding the toxicity and inflammatory potential of fullerenols give
      conflicting conclusions. To further elucidate the potential for toxicity of
      fullerenols, human epidermal keratinocytes (HEK) were exposed to fullerenols (low
      (C60(OH)20), medium (C60(OH)24), and high (C60(OH)32)) at concentrations ranging
      from 0.000544-42.5 MUg/ml for 24 and 48 h. A statistically significant (p<0.05)
      decrease in viability with alamar Blue (aB) was noted only with C60(OH)32 at 42.5
      MUg/ml after 24 h. Nanoparticle (NP) controls showed minimal NP/assay
      interference of the three fullerenols with the aB viability assay. Normalized IL
      8 concentration for C60(OH)20 was not significantly different from control, while
      C60(OH)24 and C60(OH)32 showed a significant decrease at 24 and 48 h. These
      results suggest that different hydroxylation of fullerenes caused no cytotoxicity
      or inflammation up to 8.55 MUg/ml. These findings suggest that extrapolation
      across similar NP will be dependent upon surface chemistry and concentration
      which may affect the degree of agglomeration and thus biological effects.

PMID- 21964475
TI  - Combination of withaferin A and X-ray irradiation enhances apoptosis in U937
      cells.
AB  - Combined treatment with radiation has improved the outcome in various cancers and
      many radiosensitizers are used to enhance the therapeutic efficiency of
      radiotherapy. Withaferin A (Wit A), a natural compound derived from the medicinal
      plant Withania somnifera, has been reported for its anti-inflammatory and anti
      tumor effects. In this study, we show that Wit A enhances the ionizing radiation
      (IR)-induced apoptosis in human lymphoma U937 cells. Wit A-enhanced IR-induced
      apoptosis is associated with the PARP cleavage, caspase-3 activation, as well as
      specifically down-regulation of anti-apoptotic protein Bcl-2, suggesting that Wit
      A may be useful as a potential radiosensitizer. In addition, pretreatment of U937
      cells with SP600125 (JNK inhibitor) or SB203589 (p38 MAPK inhibitor) dose
      dependently inhibited the proteolytic cleavage of PARP. We provide the evidence
      here that generation of reactive oxygen species (ROS), Bcl-2 down-regulation and
      activation of MAPKs pathway are critically involved in the apoptosis induced by
      Wit A and radiation.

PMID- 21964476
TI  - Cytotoxicity of 3-(3,5-dichlorophenyl)-2,4-thiazolidinedione (DCPT) and analogues
      in wild type and CYP3A4 stably transfected HepG2 cells.
AB  - The thiazolidinedione (TZD) ring is a constituent of the glitazones that are used
      to treat type II diabetes. Liver injury has been reported following chronic
      glitazone use; however, they do not produce hepatic damage in common laboratory
      animal species. In contrast, 3-(3,5-dichlorophenyl)-2,4-thiazolidinedione (DCPT)
      causes hepatotoxicity in rats. DCPT toxicity is dependent upon the presence of an
      intact TZD ring and cytochrome P450 (CYP)-mediated biotransformation. To further
      investigate TZD ring-induced toxicity, DCPT and several structural analogues or
      potential metabolites were tested in vitro using wild type human hepatoma HepG2
      and HepG2 cells stably transfected with the CYP3A4 isozyme. CYP3A4 activity was
      confirmed by measuring testosterone 6beta-hydroxylation. Both cell lines were
      treated with 0-250 MUM of the compounds in Hanks' balanced salt solution. Cell
      viability was measured after 24 h. DCPT and S-(3,5-dichlorophenyl)aminocarbonyl
      thioglycolic acid (DCTA) were the most toxic compounds of the series.
      Furthermore, DCPT was significantly more toxic in transfected cells (LC50=160.2+/
      5.9 MUM) than in wild type cells (LC50=233.0+/-19.7 MUM). Treatment with a CYP3A4
      inhibitor or inducer attenuated or potentiated DCPT cytotoxicity, respectively.
      These results suggest that DCPT-induced cytotoxicity in the transfected HepG2
      cells is partially dependent on CYP3A4.

PMID- 21964478
TI  - CsSCL1 is differentially regulated upon maturation in chestnut microshoots and is
      specifically expressed in rooting-competent cells.
AB  - The Castanea sativa SCL1 gene (CsSCL1) has previously been shown to be induced by
      auxin during adventitious root (AR) formation in rooting-competent microshoots.
      However, its expression has not previously been analyzed in rooting-incompetent
      shoots. This study focuses on the regulation of CsSCL1 during maturation and the
      role of the gene in the formation of AR. The expression of CsSCL1 in rooting
      incompetent microshoots and other tissues was investigated by quantitative
      reverse transcriptase--polymerase chain reaction. The analysis was complemented
      by in situ hybridization of the basal segments of rooting-competent and -
      incompetent microshoots during AR induction, as well as in AR and lateral roots.
      It was found that CsSCL1 is upregulated by auxin in a cell-type- and phase
      dependent manner during the induction of AR. In root-forming shoots, CsSCL1 mRNA
      was specifically located in the cambial zone and derivative cells, which are
      rooting-competent cells, whereas in rooting-incompetent shoots the hybridization
      signal was more diffuse and evenly distributed through the phloem and parenchyma.
      CsSCL1 expression was also detected in lateral roots and axillary buds. The
      different CsSCL1 expression patterns in rooting-competent and -incompetent
      microshoots, together with the specific location of transcripts in cell types
      involved in root meristem initiation and in the root primordia of AR and lateral
      roots, indicate an important role for the gene in determining whether certain
      cells will enter the root differentiation pathway and its involvement in meristem
      maintenance.

PMID- 21964477
TI  - Okadaic acid induces apoptosis through the PKR, NF-kappaB and caspase pathway in
      human osteoblastic osteosarcoma MG63 cells.
AB  - Okadaic acid (OA) is the major component of diarrheic shellfish poisoning toxins
      and a potent inhibitor of protein phosphatase 1 and 2A. However, the underlying
      regulatory mechanisms involved in OA-induced cell death are not well understood.
      In the present study, we examined the effects of OA on apoptosis of MG63 cells by
      characterizing apoptotic morphological changes of the cells and DNA
      fragmentation. The roles of double-stranded RNA-dependent protein kinase (PKR),
      nuclear factor-kappaB (NF-kappaB) and caspase in OA-mediated apoptosis in MG63
      cells were also examined. Results showed that OA induced cytotoxicity and
      apoptosis in MG63 cells at IC50 of 75 nM. A functional PKR pathway is required to
      induce apoptosis in response to OA treatment. Blockade of NF-kappaB by ammonium
      pyrrolidinedithiocarbamate (PDTC) resulted in down-regulation of apoptosis. The
      caspase-3 and caspase-8 inhibitors blocked apoptosis in MG63 cells. In
      conclusion, our results imply that OA can induce MG63 cell apoptosis through the
      PKR, NF-kappaB and caspase pathway.

PMID- 21964479
TI  - Egg freezing for non-medical uses: the lack of a relational approach to autonomy
      in the new Israeli policy and in academic discussion.
AB  - Recently, the Israel National Bioethics Council (INBC) issued recommendations
      permitting egg freezing to prevent both disease- and age-related fertility
      decline. The INBC report forms the basis of Israel's new policy, being one of the
      first countries to regulate and authorise egg freezing for what it considers to
      be non-medical (ie, social) uses. The ethical discussion in the INBC report is
      reviewed and compared with the scant ethical discourse in the academic literature
      on egg freezing as a means of preventing age-related loss of fertility. We argue
      that both the INBC recommendations and the bioethical academic discourse on egg
      freezing are grounded in liberal ideology, which views technology as primarily
      enabling. Accordingly, they promote 'individual autonomy' as exercised through
      informed consent. Our study suggests that a relational approach to autonomy may
      be a more suitable model for considering women's choices about egg freezing.

PMID- 21964480
TI  - From simple graphs to the connectome: networks in neuroimaging.
AB  - Connectivity is fundamental for understanding the nature of brain function. The
      intricate web of synaptic connections among neurons is critically important for
      shaping neural responses, representing statistical features of the sensory
      environment, coordinating distributed resources for brain-wide processing, and
      retaining a structural record of the past in order to anticipate future events
      and infer their relations. The importance of brain connectivity naturally leads
      to the adoption of the theoretical framework of networks and graphs. Network
      science approaches have been productively deployed in other domains of science
      and technology and are now beginning to make contributions across many areas of
      neuroscience. This article offers a personal perspective on the confluence of
      networks and neuroimaging, charting the origins of some of its major intellectual
      themes.

PMID- 21964481
TI  - The P300 event-related brain potential as a neurobiological endophenotype for
      substance use disorders: a meta-analytic investigation.
AB  - Endophenotypes are intermediate phenotypes on the putative causal pathway from
      genotype to phenotype and can aid in discovering the genetic etiology of a
      disorder. There are currently very few suitable endophenotypes available for
      substance use disorders (SUD). The amplitude of the P300 event-related brain
      potential is a possible candidate. The present study determined whether the P300
      amplitude fulfils two fundamental criteria for an endophenotype: (1) an
      association with the disorder (disease marker), and (2) presence in unaffected
      biological relatives of those who have the disorder (vulnerability marker). For
      this purpose, two separate meta-analyses were performed. Meta-analysis 1
      investigated the P300 amplitude in relation to SUD in 39 studies and Meta
      analysis 2 investigated P300 amplitude in relation to a family history (FH+) of
      SUD in 35 studies. The findings indicate that a reduced P300 amplitude is
      significantly associated with SUD (d=0.51) and, though to a lesser extent, with a
      FH+ of SUD (d=0.28). As a disease maker, the association between reduced P300
      amplitude and SUD is significantly larger for participants that were exclusively
      recruited from treatment facilities (d=0.67) than by other methods (i.e.,
      community samples and family studies; d=0.45 and 0.32, respectively), and larger
      for abstinent SUD patients (d=0.71) than for current substance users (d=0.37).
      Furthermore, in contrast to FH+ males, a P300 amplitude reduction seems not to be
      present in FH+ females (d=-0.07). Taken together, these results suggest that P300
      amplitude reduction can be both a useful disease and vulnerability marker and is
      a promising neurobiological endophenotype for SUD, though only in males.
      Implications and future directions are discussed.

PMID- 21964482
TI  - Aromatic pathways in mono- and bisphosphorous singly Mobius twisted [28] and
      [30]hexaphyrins.
AB  - Magnetically induced current densities and strengths of currents passing through
      selected bonds have been calculated for monophosphorous [28]hexaphyrin
      ((PO)[28]hp) and for bisphosphorous [30]hexaphyrin ((PO)(2)[30]hp) at the density
      functional theory level using our gauge-including magnetically induced current
      (GIMIC) approach. The current-density calculations yield quantitative information
      about electron-delocalization pathways and aromatic properties of singly Mobius
      twisted hexaphyrins. The calculations confirm that (PO)[28]hp sustains a strong
      diatropic ring current (susceptibility) of 15 nA T(-1) and can be considered
      aromatic, whereas (PO)(2)[30]hp is antiaromatic as it sustains a paratropic ring
      current of -10 nA T(-1). Numerical integration of the current density passing
      through selected bonds shows that the current is generally split at the pyrroles
      into an outer and an inner pathway. For the pyrrole with the NH moiety pointing
      outwards, the diatropic ring current of (PO)[28]hp takes the outer route across
      the NH unit, whereas for (PO)(2)[30]hp, the paratropic ring current passes
      through the inner C(beta)=C(beta) double bond. The main diatropic ring current of
      (PO)[28]hp generally prefers the outer routes at the pyrroles, whereas the
      paratropic ring current of (PO)(2)[30]hp prefers the inner ones. In some cases,
      the ring current is rather equally split along the two pathways at the pyrroles.
      The calculated ring-current pathways do not agree with those deduced from
      measured (1)H NMR chemical shifts.

PMID- 21964483
TI  - Screening for bipolar disorder among outpatients with substance use disorders.
AB  - BACKGROUND: Comorbidity of bipolar disorder and alcohol or substance
      abuse/dependence is frequent and has marked negative consequences on the course
      of the illness and treatment compliance. The objective of this study was to
      compare the validity of two short instruments aimed at screening bipolar
      disorders among patients treated for substance use disorders. METHODS: The Mood
      Disorder Questionnaire (MDQ) and the Hypomania Checklist-32 (HCL-32) were tested
      with reference to the mood section of the Structured Clinical Interview for DSM
      IV axis I disorders (SCID) in 152 patients, recruited in two outpatient clinics
      providing specialized treatment for alcohol and opiate dependence. RESULTS:
      According to the SCID, 33 patients (21.7%) had a diagnosis within the bipolar
      spectrum (two bipolar I, 21 bipolar II and 10 bipolar not otherwise specified).
      The HCL-32 was more sensitive (90.9% vs. 66.7%) and the MDQ more specific (38.7%
      vs. 77.3%) for the whole sample. The MDQ displayed higher sensitivity and
      specificity in patients treated for alcohol than for opiate dependence, whereas
      the HCL-32 was highly sensitive but poorly specific in both samples. Both
      instruments had a positive predictive value under 50%. CONCLUSIONS: Caution is
      needed when using the MDQ and HCL-32 in patients treated for substance use
      disorders.

PMID- 21964484
TI  - Oral disease in relation to future risk of dementia and cognitive decline:
      prospective cohort study based on the Action in Diabetes and Vascular Disease:
      Preterax and Diamicron Modified-Release Controlled Evaluation (ADVANCE) trial.
AB  - OBJECTIVE: Examine the association of oral disease with future dementia/cognitive
      decline in a cohort of people with type 2 diabetes. METHODS: A total of 11,140
      men and women aged 55-88 years at study induction with type 2 diabetes
      participated in a baseline medical examination when they reported the number of
      natural teeth and days of bleeding gums. Dementia and cognitive decline were
      ascertained periodically during a 5-year follow-up. RESULTS: Relative to the
      group with the greatest number of teeth (more than or equal to 22), having no
      teeth was associated with the highest risk of both dementia (hazard ratio; 95%
      confidence interval: 1.48; 1.24, 1.78) and cognitive decline (1.39; 1.21, 1.59).
      Number of days of bleeding gums was unrelated to these outcomes. CONCLUSIONS:
      Tooth loss was associated with an increased risk of both dementia and cognitive
      decline.

PMID- 21964485
TI  - C-reactive protein as a marker of cardiovascular disease in patients with a
      schizophrenia spectrum disorder treated in routine medical practice.
AB  - OBJECTIVE: Interest in cardiovascular diseases (CVD) in schizophrenia has grown
      recently due to documented incremental mortality. C-reactive protein (CRP) has
      been assessed as a marker in individuals with CVD and/or at high risk of
      developing it. However, its role in schizophrenia patients is unknown. The goal
      of this research was thus to explore the use of CRP as a marker of CVD risk in
      patients with schizophrenia. METHODS: A cross-sectional analysis of the Badalona
      Serveis Assistencials (BSA) administrative claims database was conducted
      including all subjects aged>18 years with a diagnosis of schizophrenia spectrum
      disorder. CRP measurement, sociodemographics, medical history, 10-year CVD risk
      (Framingham function) and clinical chemistry data were extracted for analysis.
      RESULTS: Seven hundred and five patients (53.0% men, 48.2 [15.8] years, 78.7% on
      atypicals) met criteria for analysis. Mean 10-year CVD risk was high; 11.9+/-5.7%
      and mean CRP levels were 2.6+/-2.5 mg/L with 30.4% showing above-normative levels
      (>3 mg/L). After adjusting for age, gender, smoking and presence of neoplasm or
      inflammatory diseases, CRP was linearly associated with 10-year CVD risk
      stratified by risk (low, moderate, high/very high): respectively, 2.3 (95% CI:
      2.1-2.5), 3.1 (2.6-3.5) and 3.7 (3.2-4.1) mg/L; F=13.5, P<0.001. Patients with
      known CVD also showed higher CRP levels: 3.7 (2.9-4.5) vs. 2.5 (2.4-2.7) mg/L,
      P=0.008; and higher probability of above-normal values; odds ratio=4.71 (2.01
      11.04), P<0.001. CONCLUSIONS: High CRP levels above normative were associated
      with both known CVD and high/very high 10-year risk of a CVD event in patients
      with schizophrenia, suggesting CRP could be a marker of CVD in this psychiatric
      disorder.

PMID- 21964486
TI  - How does the ryanodine receptor in the ventricular myocyte wake up: by a single
      or by multiple open L-type Ca2+ channels?
AB  - We study here the early stage of Ca(2+)-induced Ca(2+) release (CICR) in the
      diadic cleft of cardiac ventricular myocytes. A crucial question for this
      mechanism is whether the activation of the ryanodine receptors (RyRs) is
      triggered by one or by multiple open L-type Ca(2+) channels (LCCs). We address
      the problem through a modelling approach that allows us to investigate both
      possibilities. The model is based on a spatially resolved description of a Ca(2+)
      release unit (CaRU), consisting of the junctional sarcoplasmic reticulum and the
      diadic cleft, with well-defined channel placement. By taking advantage of largely
      varying time scales of the Ca(2+) dynamics in the diadic cleft, the governing
      equations can be reduced to one ordinary differential equation that describes the
      Ca(2+) fluxes, the electric field due to surface charges and diffusion. Our study
      shows that the mechanisms of the early stage of CICR shape measurable properties
      of CICR in a characteristic way. From here we conclude that the activation of
      RyRs requires multiple open LCCs.

PMID- 21964487
TI  - Platelet-rich plasma induces increased expression of G1 cell cycle regulators,
      type I collagen, and matrix metalloproteinase-1 in human skin fibroblasts.
AB  - Platelet-rich plasma (PRP) is derived from fresh whole blood, which contains a
      high concentration of platelets. Recently, PRP has been used for skin wound
      healing and rejuvenation. However, the molecular mechanisms underlying PRP
      inducing wound healing processes are still largely unknown. The aim of this study
      is to evaluate the effect of PRP on the expression of G1 cell cycle regulatory
      proteins, type I collagen, matrix metalloproteinase-1 (MMP-1), and MMP-2 in human
      skin fibroblasts (HSF). We performed a cell proliferation and a migration assay,
      immunoblotting, and a chloramphenicol acetyltransferase (CAT) assay in PRP
      treated human skin fibroblasts. PRP treatment induced increased rates of cell
      proliferation and cell migration. Expression of cyclin A protein was increased by
      a low concentration (0.5%) of PRP-treated HSF. In addition, expression of Rb,
      cyclin E, and cyclin-dependent kinase 4 proteins was increased by a high
      concentration (5%) of PRP-treated HSF. High concentration of PRP induced an up
      regulation of type I collagen, MMP-1, and MMP-2 expression in HSF. Taken
      together, PRP treatment induced an increase in expression of G1 cell cycle
      regulators, type I collagen and MMP-1, thereby accelerating the wound healing
      process.

PMID- 21964488
TI  - Dorsolateral and ventromedial prefrontal cortex orchestrate normative choice.
AB  - Humans are noted for their capacity to over-ride self-interest in favor of
      normatively valued goals. We examined the neural circuitry that is causally
      involved in normative, fairness-related decisions by generating a temporarily
      diminished capacity for costly normative behavior, a 'deviant' case, through non
      invasive brain stimulation (repetitive transcranial magnetic stimulation) and
      compared normal subjects' functional magnetic resonance imaging signals with
      those of the deviant subjects. When fairness and economic self-interest were in
      conflict, normal subjects (who make costly normative decisions at a much higher
      frequency) displayed significantly higher activity in, and connectivity between,
      the right dorsolateral prefrontal cortex (DLPFC) and the posterior ventromedial
      prefrontal cortex (pVMPFC). In contrast, when there was no conflict between
      fairness and economic self-interest, both types of subjects displayed identical
      neural patterns and behaved identically. These findings suggest that a
      parsimonious prefrontal network, the activation of right DLPFC and pVMPFC, and
      the connectivity between them, facilitates subjects' willingness to incur the
      cost of normative decisions.

PMID- 21964489
TI  - In utero exposure to cocaine delays postnatal synaptic maturation of
      glutamatergic transmission in the VTA.
AB  - Maternal exposure to cocaine may perturb fetal development and affect synaptic
      maturation in the offspring. However, the molecular mechanism underlying such
      changes remains elusive. We focused on the postnatal maturation of glutamatergic
      transmission onto ventral tegmental area dopamine neurons in the mouse. We found
      that, during the first postnatal week, transmission was dominated by calcium
      permeable AMPA receptors and GluN2B-containing NMDA receptors. Subsequently,
      mGluR1 receptors drove synaptic insertion of calcium-impermeable AMPA receptors
      and GluN2A-containing NMDAR. When pregnant mice were exposed to cocaine, this
      glutamate receptor switch was delayed in offspring as a result of a direct effect
      of cocaine on the fetal dopamine transporter and impaired mGluR1 function.
      Finally, positive modulation of mGluR1 in vivo was sufficient to rescue
      maturation. These data identify the molecular target through which in utero
      cocaine delays postnatal synaptic maturation, reveal the underlying expression
      mechanism of this impairment and propose a potential rescue strategy.

PMID- 21964491
TI  - Effects of increased white blood cell count on retinal perfusion during hyperoxia
      induced vasoconstriction.
AB  - PURPOSE: Several studies have shown that administration of granulocyte-colony
      stimulating factor (G-CSF) is followed by an increase of white blood cell (WBC)
      count. There is evidence from other vascular beds that an increase in WBC count
      impairs blood flow regulation especially in the microcirculation. Whether this
      also holds true for the ocular circulation is yet unknown. In the following trial
      we investigated whether an increase in WBC count alters the oxygen induced
      vasoconstriction of retinal vessels. METHODS: The study design was randomized,
      double-masked, placebo-controlled with two parallel groups. 24 healthy, male
      subjects were included. Measurements of retinal white blood cell flux with the
      blue-field entoptic technique, red blood cell velocity using the laser Doppler
      velocimeter and retinal vessel diameter using a Retinal Vessel Analyzer, were
      assessed at baseline and after breathing of 100% oxygen over 20 min. Thereafter
      300 MUg of G-CSF or placebo was administered. Measurements were repeated after
      another inhalation of 100% oxygen 8h later. RESULTS: G-CSF did not show any
      influence on systemic hemodynamics. WBC count increased significantly from 5.7 +/
      1.6 * 10(9)/L at baseline up to 19.5 +/- 4.8 * 10(9)/L 8h after G-CSF
      administration. As expected, oxygen breathing induced a pronounced
      vasoconstriction and a decrease red and white cell flux in both, the placebo and
      the G-CSF group (p<0.01 for both groups). Administration of G-CSF increased WBC
      flux, but did not affect red blood cell flux. The response of red blood cell flux
      and retinal vessel diameters to hyperoxia was not altered by G-CSF
      administration. However, leukocytosis leads to a more pronounced oxygen induced
      reduction in red blood cell velocity compared to the placebo group (p=0.024).
      CONCLUSION: Our data indicate that increased WBC count as induced with G-CSF,
      leads to a more pronounced reduction in retinal red blood cell flux during states
      of vasoconstriction. This indicates that, as in other vascular beds, an increase
      in WBC leads to an altered blood flow regulation.

PMID- 21964490
TI  - A dual shaping mechanism for postsynaptic ephrin-B3 as a receptor that sculpts
      dendrites and synapses.
AB  - As the neural network becomes wired, postsynaptic signaling molecules are thought
      to control the growth of dendrites and synapses. However, how these molecules are
      coordinated to sculpt postsynaptic structures is less well understood. We find
      that ephrin-B3, a transmembrane ligand for Eph receptors, functions
      postsynaptically as a receptor to transduce reverse signals into developing
      dendrites of mouse hippocampal neurons. Both tyrosine phosphorylation-dependent
      GRB4 SH2/SH3 adaptor-mediated signals and PSD-95-discs large-zona occludens-1
      (PDZ) domain-dependent signals are required for inhibition of dendrite branching,
      whereas only PDZ interactions are necessary for spine formation and excitatory
      synaptic function. PICK1 and syntenin, two PDZ domain proteins, participate with
      ephrin-B3 in these postsynaptic activities. PICK1 has a specific role in spine
      and synapse formation, and syntenin promotes both dendrite pruning and synapse
      formation to build postsynaptic structures that are essential for neural
      circuits. The study thus dissects ephrin-B reverse signaling into three distinct
      intracellular pathways and protein-protein interactions that mediate the
      maturation of postsynaptic neurons.

PMID- 21964492
TI  - Hemispheric differences over frontal theta-band power discriminate between
      stimulus- versus memory-driven saccadic eye movement.
AB  - Although several electrophysiological studies have demonstrated the role of theta
      band during the execution of different visuospatial attention tasks, this study
      is the first to directly investigate the role of theta power during the planning,
      execution and cognitive control of saccadic eye movements (SEMs). The current
      study aims at addressing this issue by investigating absolute theta power over
      the frontal cortex during the execution of random and fixed SEMs. Twelve healthy
      volunteers, performed two tasks involving different conditions in the planning,
      execution and cognitive control of SEMs while their brain activity pattern was
      recorded using quantitative electroencephalography. We found an interaction
      between SEM condition and electrode (F3, F4, Fz), and a main effect of time point
      and electrode. Our key finding revealed that the stimulus presentation induces
      different patterns over frontal theta power increase between the left and right
      hemisphere. We conclude that right and left frontal regions are an important
      factor to discriminate between memory- versus stimulus-driven SEMs, and speculate
      on their different contributions to visuospatial attention.

PMID- 21964493
TI  - Expression of chemokine-like factor 1 after focal cerebral ischemia in the rat.
AB  - Cerebral ischemic injury is associated with the induction of a series of pro
      inflammatory mediators such as cytokines and chemokines. The chemokine-like
      factor 1(CKLF1), as a novel human cytokine, displays chemotactic activities in a
      wide spectrum of leukocytes. The present study was conducted to determine if
      CKLF1 was produced in the brain of rats subjected to transient middle cerebral
      artery occlusion (TMCAO). Therefore, RT-PCR, Western blot and
      immunohistochemistry were utilized to characterize the expression of CKLF1 at
      different times after TMCAO. The result showed that almost no expression of CKLF1
      was found in the sham-operated or contralateral cerebral cortex and hippocampus.
      CKLF1 expression significantly increased in the ischemic cerebral cortex and
      hippocampus, elevating at 12 h and peaking at 2 days after reperfusion. CKLF1
      positive staining was mainly present in the cerebral cortex, hippocampus,
      thalamus, and hypothalamus. These results demonstrate that the expression of
      CKLF1 increases after focal cerebral ischemia in rat brain. Thus, CKLF1 may be a
      potential therapeutic target for cerebral ischemia.

PMID- 21964494
TI  - An arthropod deterrent attracts specialised bees to their host plants.
AB  - Many bee species are adapted to just a few specific plants in order to collect
      pollen (oligolecty). To reproduce successfully, it is important for oligolectic
      bees to find and recognise the specific host flowers. In this study, we
      investigated the role of floral volatiles used by an oligolectic bee to recognise
      its host plants. We compared the attractiveness of natural and synthetic scent
      samples of host flowers to foraging-naive and -experienced Hoplitis adunca
      (Megachilidae) bees that are specialised on Echium and Pontechium (Boraginaceae)
      plants. The investigations showed that naive H. adunca females are attracted to
      1,4-benzoquinone. During their lifetime, bees learn additional floral cues while
      foraging on host flowers. In contrast to naive ones, experienced H. adunca
      females use, in addition to 1,4-benzoquinone, other compounds to recognise their
      host plants. 1,4-Benzoquinone is an uncommon floral compound only known from the
      host plants of H. adunca, and is therefore ideally suited to be used as a plant
      specific recognition cue. Several arthropods use this compound to deter insect
      predators. Therefore, 1,4-benzoquinone as an attractant in Echium flowers may
      have evolved from a primary function as a defensive compound against insect
      herbivores.

PMID- 21964495
TI  - The influence of patellar dislocation on the femoro-tibial loading during total
      knee arthroplasty.
AB  - PURPOSE: Balancing the gap is essential in total knee arthroplasty (TKA). The
      purpose of this study was to quantify the influence of patellar position on
      femoro-tibial joint load in TKA. We hypothesized that resetting of the patella
      increased medial joint load and decreased lateral joint load. METHODS: Our
      original tensor system was used during posterior-stabilized (PS) and cruciate
      retaining (CR) total knee arthroplasty (TKA) using medial para-patellar approach
      (MPP) or sub-vastus approach (SV). RESULTS: In PS-TKA, by resetting the patella,
      the ratios between medial and lateral compartments were not changed in both
      extension and flexion position using MPP and were significantly changed in
      flexion position using SV. In CR-TKA, by resetting the patella, the load of the
      lateral component decreased and the ratios between medial and lateral
      compartments were changed significantly in both extension and flexion position
      using SV. CONCLUSION: It is important to be aware that, when performing CR-KA,
      the load of the lateral compartment will decrease by resetting the patella using
      SV.

PMID- 21964496
TI  - Current practice in shoulder pathology: results of a web-based survey among a
      community of 1,084 orthopedic surgeons.
AB  - PURPOSE: The aim of this study was to report orthopedic surgeons' management of
      choice for difficult clinical scenarios of shoulder pathologies. METHODS: A web
      questionnaire was developed including four clinical scenarios of shoulder
      pathologies. Subsequently, opinions were solicited from more than 1,000 members
      of an international association of surgeons specialized in sports traumatology
      and knee surgery (ESSKA). RESULTS: The response rate was 40% (412
      questionnaires). For scenario 1, first anterior dislocation of the shoulder, the
      most indicated treatment for 71% of respondents was an arthroscopic Bankart
      repair (P < 0.001). For scenario 2, shoulder arthritis with concentric erosion
      and cuff tear, 38% chose a shoulder replacement, while 37% preferred a
      supraspinatus tendon repair in combination with long head of biceps (LHB)
      tenodesis or tenotomy. For scenario 3, large tendon tears with 70% fatty
      infiltration of the infraspinatus tendon and lateral LHB instability, 70% of
      surgeons considered that, among conservative treatments, hyaluronic acid
      injection was not an appropriate management. Arthroscopic rotator cuff repair,
      arthroscopic acromioplasty, and LHB tenotomy gained larger consensus (81, 80, and
      79% of respondents, respectively). A double-row technique for rotator cuff repair
      was preferred to a single-row technique (P = 0.02). Scenario 4, adhesive
      capsulitis, split the respondents equally, with 51% in favor of a surgical
      approach and 49% in favor of a conservative approach (N.S.). CONCLUSIONS: On-line
      questionnaires have the potential to improve knowledge about current trends in
      clinical practice and can help orthopedic surgeons to develop guidelines. LEVEL
      OF EVIDENCE: Cross-sectional; Level V (expert opinion).

PMID- 21964497
TI  - Prospectively ECG-triggered high-pitch spiral acquisition for cardiac CT
      angiography in routine clinical practice: initial results.
AB  - PURPOSE: This study was conducted to evaluate the mode of application, image
      quality (IQ), and radiation exposure resulting from introduction of a
      prospectively electrocardiogram-triggered high-pitch cardiac computed tomography
      angiography (CTA) acquisition mode into routine clinical practice. MATERIALS AND
      METHODS: A total of 42 prospectively triggered cardiac CTAs were conducted on 34
      patients (11 female, 23 male; mean age 56 +/- 15 y) using a high-pitch mode
      (pitch 3.4) on a dual-source CT. In 8 of these patients with higher heart rates
      or occasional premature ventricular contractions, 2 immediately subsequent CTAs
      were performed ("double flash protocol"). Subjective IQ was assessed for coronary
      arteries using a 4-point scale (1=unevaluable to 4=excellent). Contrast-to-noise
      ratio (CNR) was measured in 9 locations. CT Dose Index and dose-length product
      were obtained, and the patients' effective dose was calculated. RESULTS: Mean
      effective doses were 2.6 +/- 1.4 mSv (range: 1.1 to 6.4) for the entire cardiac
      examination and 1.4 +/- 0.7 mSv (0.4 to 3.1) for individual high-pitch cardiac
      CTA. z-coverage ranged from 9.9 cm in a native coronary CTA to 31.4 cm in a
      bypass graft case. The overall subjective IQ was good to excellent (mean score:
      3.5), with 1.5% unevaluable coronary segments. The "double flash protocol"
      resulted in a fully diagnostic CT study in all cases just after taking both scans
      into consideration. The mean CNR of all locations was 19.7 +/- 2.6. CONCLUSION:
      Prospectively electrocardiograph-triggered high-pitch-mode cardiac CTA is a
      feasible and promising technique in clinical routine, allowing for evaluation of
      coronaries at good-to-excellent IQ and providing high CNR and minimal radiation
      doses. The "double flash protocol" might become a more robust tool in patients
      with elevated heart rates or premature ventricular contractions.

PMID- 21964498
TI  - An affinity purification procedure to isolate oxidized p53.
AB  - Oxidation of cysteine is now known to serve as a fundamental mechanism to control
      protein function or activity. Many redox-regulated proteins do not oxidize to
      homogeneity, resulting in a mixture of reduced and oxidized species which cannot
      be separated chromatographically. Here we describe a protocol for the separation
      of reduced and oxidized forms of the tumor suppressor protein p53. This
      purification method relies on the reversible labeling of thiol groups with biotin
      and exploitation of the ultrastrong biotin-avidin interaction. This purification
      procedure can be applied to other cysteine-containing proteins where enrichment
      of the oxidized form is required.

PMID- 21964499
TI  - Poly(acrylic acid)-cysteine for oral vitamin B12 delivery.
AB  - The aim of this study was to investigate the potential of poly(acrylic acid)
      cysteine (PAA-cys) solution and microparticles to enhance the transport of
      vitamin B12 (VB 12) across Caco-2 cell monolayer and rat intestinal mucosa.
      Thiolated PAA was synthesized by covalent attachment of L-cysteine.
      Microparticles were prepared by spray-drying and characterized regarding their
      size, morphology, thiol group content, VB 12 payload and release, swelling
      behavior, mucoadhesion, permeation-enhancing effect, and cytotoxicity. Particles
      with a mean diameter of 2.452+/-2.26 MUm, a payload of 1.11+/-0.72%, and 190.2+/
      8.85 MUmol of free thiol groups per gram were prepared. Swelling behavior studies
      revealed that the stability of thiolated particles was improved compared with
      unmodified ones. Of the total VB 12 loaded, 95+/-0.12% was released within 3 h
      from thiolated particles. PAA-cys particles exhibited 2.24-fold higher
      mucoadhesive properties compared with unmodified particles. Permeation
      experiments with Caco-2 cells proved that permeability of VB 12 with PAA-cys
      solution and particles was 3.8- and 3.6-fold higher than control, respectively,
      and with rat intestinal mucosa it was 4.8- and 4.4-fold higher than control,
      respectively. Negligible cytotoxicity was assessed. PAA-cys is a promising
      excipient for oral delivery of VB 12 as a solution and as microparticles.

PMID- 21964500
TI  - Chemiluminometric evaluation of melatonin and selected melatonin precursors'
      interaction with reactive oxygen and nitrogen species.
AB  - Melatonin is a hormone, a derivative of tryptophan, that possesses a potent
      scavenging capacity for the most reactive and dangerous free radicals, being an
      important protection against oxidative stress. In this work, an automated flow
      based procedure for assessment of melatonin, tryptophan, and 5-hydroxytryptophan
      scavenging capacity was developed. The presented methodology involved a multi
      pumping flow system and exploited the ability of selected compounds to inhibit
      the chemiluminescence reaction of luminol with hydrogen peroxide, hydroxyl
      radical, and peroxynitrite anion. The system was based on the use of several
      solenoid actuated micro-pumps as the only active components of the flow manifold.
      This enabled the reproducible insertion and efficient mixing of very low volumes
      of sample and reagents as well as the transportation of the sample zone toward
      detection for monitoring the chemiluminometric response. Furthermore, the high
      versatility of the proposed multi-pumping flow system allowed the implementation
      of distinct reactions for the in-line generation of the different reactive
      species assayed without requiring physical reconfiguration. The results obtained
      demonstrated that 5-hydroxytryptophan is the most potent scavenger, followed by
      melatonin and tryptophan. The developed multi-pumping flow system exhibited good
      measurement precision (relative standard deviations typically <2%, n=10), low
      operational costs, and low reagent consumption.

PMID- 21964501
TI  - Isothermal titration calorimetry and surface plasmon resonance allow quantifying
      substrate binding to different binding sites of Bacillus subtilis xylanase.
AB  - Isothermal titration calorimetry and surface plasmon resonance were tested for
      their ability to study substrate binding to the active site (AS) and to the
      secondary binding site (SBS) of Bacillus subtilis xylanase A separately. To this
      end, three enzyme variants were compared. The first was a catalytically
      incompetent enzyme that allows substrate binding to both the AS and SBS. In the
      second enzyme, binding to the SBS was impaired by site-directed mutagenesis,
      whereas in the third enzyme, the AS was blocked using a covalent inhibitor. Both
      techniques were able to show that AS and SBS have a similar binding affinity.

PMID- 21964503
TI  - Multiply charged ions in the gas phase.

PMID- 21964502
TI  - Measurement of human plasma proteome dynamics with (2)H(2)O and liquid
      chromatography tandem mass spectrometry.
AB  - Dysfunction of protein turnover is a feature of many human diseases, and proteins
      are substrates in important biological processes. Currently, no method exists for
      the measurement of global protein turnover (i.e., proteome dynamics) that can be
      applied in humans. Here we describe the use of metabolic labeling with deuterium
      ((2)H) from (2)H(2)O and liquid chromatography tandem mass spectrometry (LC
      MS/MS) analysis of mass isotopomer patterns to measure protein turnover. We show
      that the positions available for (2)H label incorporation in vivo can be
      calculated using peptide sequence. The isotopic incorporation values calculated
      by combinatorial analysis of mass isotopomer patterns in peptides correlate very
      closely with values established for individual amino acids. Inpatient and
      outpatient heavy water labeling protocols resulted in (2)H label incorporation
      sufficient for reproducible quantitation in humans. Replacement rates were
      similar for peptides deriving from the same protein. Using a kinetic model to
      account for the time course of each individual's (2)H(2)O enrichment curves,
      dynamics of approximately 100 proteins with half-lives ranging from 0.4 to 40
      days were measured using 8 MUl of plasma. The measured rates were consistent with
      literature values. This method can be used to measure in vivo proteome
      homeostasis in humans in disease and during therapeutic interventions.

PMID- 21964504
TI  - The use of background matching vs. masquerade for camouflage in cuttlefish Sepia
      officinalis.
AB  - Cuttlefish, Sepia officinalis, commonly use their visually-guided, rapid adaptive
      camouflage for multiple tactics to avoid detection or recognition by predators.
      Two common tactics are background matching and resembling an object (masquerade)
      in the immediate area. This laboratory study investigated whether cuttlefish
      preferentially camouflage themselves to resemble a three-dimensional (3D) object
      in the immediate visual field (via the mechanism of masquerade/deceptive
      resemblance) rather than the 2D benthic substrate surrounding them (via the
      mechanisms of background matching or disruptive coloration). Cuttlefish were
      presented with a combination of benthic substrates (natural rocks or artificial
      checkerboard and grey printouts) and 3D objects (natural rocks or cylinders with
      artificial checkerboards and grey printouts glued to the outside) with visual
      features known to elicit each of three camouflage body pattern types (Uniform,
      Mottle and Disruptive). Animals were tested for a preference to show a body
      pattern appropriate for the 3D object or the benthic substrate. Cuttlefish
      responded by masquerading as the 3D object, rather than resembling the benthic
      substrate, only when presented with a high-contrast object on a substrate of
      lower contrast. Contrast is, therefore, one important cue in the cuttlefish's
      preference to resemble 3D objects rather than the benthic substrate.

PMID- 21964505
TI  - REACH exposure assessment of anticorrosive paint products--determination of
      exposure from application and service life to the aquatic environment.
AB  - The European Community Regulation on the registration, evaluation, authorisation
      and restriction of chemicals (REACH) introduced exposure scenarios describing
      safe use quantitatively, and enhancing the importance of scientific based
      exposure assessments. This paper presents methods to determine exposure from the
      airless spray application of anti-corrosive paint and leaching of painted
      articles submerged in seawater, to establish whether it is possible to test these
      exposures in a reproducible and feasible way. The paper also presents results
      from using the methods in order to assess how well the default values recommended
      under REACH coincide with the tested values and corresponding values available in
      literature. The methods used were feasible under laboratory conditions. The
      reproducibility of the application study was shown to be good and all analyses of
      the leaching showed concentrations below detection limit. More replicates will be
      required to validate the reproducibility of the growth inhibition tests. Measured
      values for the present overspray scenario were between, and the leaching values
      below, values from REACH guidelines and emission scenario documents. Further
      development of the methods is recommended.

PMID- 21964506
TI  - Induction of glutathione synthesis and heme oxygenase 1 by the flavonoids butein
      and phloretin is mediated through the ERK/Nrf2 pathway and protects against
      oxidative stress.
AB  - Butein and phloretin are chalcones that are members of the flavonoid family of
      polyphenols. Flavonoids have well-known antioxidant and anti-inflammatory
      activities. In rat primary hepatocytes, we examined whether butein and phloretin
      affect tert-butylhydroperoxide (tBHP)-induced oxidative damage and the possible
      mechanism(s) involved. Treatment with butein and phloretin markedly attenuated
      tBHP-induced peroxide formation, and this amelioration was reversed by l
      buthionine-S-sulfoximine [a glutamate cysteine ligase (GCL) inhibitor] and zinc
      protoporphyrin [a heme oxygenase 1 (HO-1) inhibitor]. Butein and phloretin
      induced both HO-1 and GCL protein and mRNA expression and increased intracellular
      glutathione (GSH) and total GSH content. Butein treatment activated the ERK1/2
      signaling pathway and increased Nrf2 nuclear translocation, Nrf2 nuclear protein
      DNA binding activity, and ARE-luciferase reporter activity. The roles of the ERK
      signaling pathway and Nrf2 in butein-induced HO-1 and GCL catalytic subunit
      (GCLC) expression were determined by using RNA interference directed against ERK2
      and Nrf2. Both siERK2 and siNrf2 abolished butein-induced HO-1 and GCLC protein
      expression. These results suggest the involvement of ERK2 and Nrf2 in the
      induction of HO-1 and GCLC by butein. In an animal study, phloretin was shown to
      increase GSH content and HO-1 expression in rat liver and decrease carbon
      tetrachloride-induced hepatotoxicity. In conclusion, we demonstrate that butein
      and phloretin up-regulate HO-1 and GCL expression through the ERK2/Nrf2 pathway
      and protect hepatocytes against oxidative stress.

PMID- 21964508
TI  - Anatomical and histological study of Liliequist's membrane: with emphasis on its
      nature and lateral attachments.
AB  - PURPOSE: In previous studies, some disagreements regarding the nature (inner or
      outer arachnoid membrane) and lateral boundaries (temporal uncus or tentorial
      edge) of Liliequist's membrane remain. The aim was to clarify whether
      Liliequist's membrane is an inner or outer arachnoid membrane, and the
      distribution of Liliequist's membrane with emphasis on its lateral attachments.
      METHODS: Liliequist's membrane was investigated by microsurgical dissection in 24
      formalin-fixed adult cadaver heads and by histological sections of sellar
      suprasellar specimens from another four formalin-fixed adult cadaver heads.
      RESULTS: The results obtained in the present study indicated that 1) Liliequist's
      membrane arises from the basal arachnoid membrane and has two components: a basal
      part comprising a folding inner layer of the arachnoid mater and an attaching
      part consisting of accumulated arachnoid trabeculae; 2) similar histological
      features are also present in other inner arachnoid membranes with attachments on
      basal arachnoid membrane, demonstrating Liliequist's membrane is an inner
      arachnoid membrane; 3) laterally, Liliequist's membrane attaches to the anterior
      tentorial edge constantly and to the mesial temporal uncus in more than half; 4)
      the oculomotor nerve courses above Liliequist's membrane and is fixed on
      Liliequist's membrane by the oculomotor membrane, which can also attach on
      temporal uncus and should be differentiated from the true temporal attachments of
      Liliequist's membrane. CONCLUSION: Liliequist's membrane is an inner rather than
      outer arachnoid membrane. Understanding of its individual variation and
      topographic relationships with surrounding neurovascular and arachnoid structures
      is important for neurosurgical practice.

PMID- 21964507
TI  - Hydrogen peroxide signaling is required for glucocorticoid-induced apoptosis in
      lymphoma cells.
AB  - Glucocorticoid-induced apoptosis is exploited clinically for the treatment of
      hematologic malignancies. Determining the required molecular events for
      glucocorticoid-induced apoptosis will identify resistance mechanisms and suggest
      strategies for overcoming resistance. In this study, we found that glucocorticoid
      treatment of WEHI7.2 murine thymic lymphoma cells increased the steady-state
      [H(2)O(2)] and oxidized the intracellular redox environment before cytochrome c
      release. Removal of glucocorticoids after the H(2)O(2) increase resulted in a 30%
      clonogenicity; treatment with PEG-CAT increased clonogenicity to 65%. Human
      leukemia cell lines also showed increased H(2)O(2) in response to glucocorticoids
      and attenuated apoptosis after PEG-CAT treatment. WEHI7.2 cells that overexpress
      catalase (CAT2, CAT38) or were selected for resistance to H(2)O(2) (200R) removed
      enough of the H(2)O(2) generated by glucocorticoids to prevent oxidation of the
      intracellular redox environment. CAT2, CAT38, and 200R cells showed a 90-100%
      clonogenicity. The resistant cells maintained pERK survival signaling in response
      to glucocorticoids, whereas the sensitive cells did not. Treating the resistant
      cells with a MEK inhibitor sensitized them to glucocorticoids. These data
      indicate that: (1) an increase in H(2)O(2) is necessary for glucocorticoid
      induced apoptosis in lymphoid cells, (2) increased H(2)O(2) removal causes
      glucocorticoid resistance, and (3) MEK inhibition can sensitize oxidative stress
      resistant cells to glucocorticoids.

PMID- 21964509
TI  - Interhemispheric hypoconnectivity in schizophrenia: fiber integrity and volume
      differences of the corpus callosum in patients and unaffected relatives.
AB  - Changes in hemispheric asymmetry and inter-hemispheric connectivity have been
      reported in schizophrenia. However, the genetic contribution to these alterations
      is still unclear. In the current study, we applied an automatic segmentation
      method to structural MRI and diffusion tensor imaging (DTI) data and examined
      volume and fiber integrity of the corpus callosum (CC), the main interhemispheric
      fiber tract, in 16 chronic schizophrenia (SZ) patients, matched first degree
      relatives and controls. SZ patients and relatives had smaller CC volumes than
      controls, particularly in the posterior genu, isthmus and splenium. Fractional
      anisotropy (FA), an indicator of fiber integrity, was reduced in patients and
      relatives in the whole CC, the inferior genu, the superior genu and the isthmus.
      Correspondingly, the mean diffusivity (MD) values of the whole CC and the isthmus
      were higher in patients and their unaffected relatives, indicating decreased
      compactness and increased intercellular space. Relatives had intermediate values
      in the volumetric and fiber integrity measurements between patients and controls.
      Lower CC volume and fiber integrity in SZ patients were associated with more
      severe auditory hallucinations. These results support the connectivity hypothesis
      of SZ (Friston, 1998) and particularly highlight the altered interhemispheric
      connectivity, which appears to be a genetic feature of SZ risk.

PMID- 21964512
TI  - Diversification in the Mexican horned lizard Phrynosoma orbiculare across a
      dynamic landscape.
AB  - The widespread montane Mexican horned lizard Phrynosoma orbiculare (Squamata:
      Phrynosomatidae) represents an ideal species to investigate the relative impacts
      of Neogene vicariance and Quaternary climate change on lineage diversification
      across the Mexican highlands. We used mitochondrial DNA to examine the maternal
      history of P. orbiculare and estimate the timing and tempo of lineage
      diversification. Based on our results, we inferred 11 geographically structured,
      well supported mitochondrial lineages within this species, suggesting P.
      orbiculare represents a species complex. Six divergences between lineages likely
      occurred during the Late Miocene and Pliocene, and four splits probably happened
      during the Pleistocene. Diversification rate appeared relatively constant through
      time. Spatial and temporal divergences between lineages of P. orbiculare and co
      distributed taxa suggest that a distinct period of uplifting of the Transvolcanic
      Belt around 7.5-3 million years ago broadly impacted diversification in taxa
      associated with this mountain range. To the north, several river drainages acting
      as filter barriers differentially subdivided co-distributed highland taxa through
      time. Diversification patterns observed in P. orbiculare provide additional
      insight into the mechanisms that impacted differentiation of highland taxa across
      the complex Mexican highlands.

PMID- 21964511
TI  - The role of religion and spirituality in psychological distress prior to surgery
      for urologic cancer.
AB  - The present study examined the associations between religion and spirituality
      (R/S), presurgical distress, and other psychosocial factors such as engagement
      coping, avoidant coping, and social support. Participants were 115 men scheduled
      for surgery for urologic cancer. Before surgery, participants completed scales
      measuring intrinsic religiosity, organized religious activity, and nonorganized
      religious activity (IR, ORA, NORA); social support (Medical Outcomes Study Social
      Support Survey); and distress (Impact of Event Scale [IES], Perceived Stress
      Scale [PSS], Brief Symptom Inventory-18 [BSI-18], and Profile of Mood States
      [POMS]). R/S was positively associated with engagement coping. Social support was
      positively associated with engagement coping and inversely associated with POMS
      and PSS scores. Engagement coping was positively associated with IES and BSI
      scores, and avoidant coping was positively associated with all distress measures.
      R/S moderated the association between engagement coping and IES scores, such that
      the association between engagement coping and IES was not significant for men
      with high R/S scores (greater religious belief). R/S moderated the association
      between social support and distress; the inverse association between social
      support and PSS and POMS scores was only significant for men who scored high on
      R/S. This study replicated findings from previous studies suggesting that
      engagement and avoidant types of coping can lead to increased distress prior to
      surgery. Although R/S was associated with engagement coping, it was not
      associated with any of the distress measures. The finding that R/S moderated the
      associations between engagement coping and distress and social support and
      distress suggests that the association between R/S, coping style, social support,
      and adjustment to stressful life situations is not simplistic, and indirect
      associations should be explored.

PMID- 21964510
TI  - Colon cancer survival with herbal medicine and vitamins combined with standard
      therapy in a whole-systems approach: ten-year follow-up data analyzed with
      marginal structural models and propensity score methods.
AB  - Although localized colon cancer is often successfully treated with surgery,
      advanced disease requires aggressive systemic therapy that has lower
      effectiveness. Approximately 30% to 75% of patients with colon cancer use
      complementary and alternative medicine (CAM), but there is limited formal
      evidence of survival efficacy. In a consecutive case series with 10-year follow
      up of all colon cancer patients (n = 193) presenting at a San Francisco Bay-Area
      center for Chinese medicine (Pine Street Clinic, San Anselmo, CA), the authors
      compared survival in patients choosing short-term treatment lasting the duration
      of chemotherapy/radiotherapy with those continuing long-term. To put these data
      into the context of treatment responses seen in conventional medical practice,
      they also compared survival with Pan-Asian medicine + vitamins (PAM+V) with that
      of concurrent external controls from Kaiser Permanente Northern California and
      California Cancer Registries. Kaplan-Meier, traditional Cox regression, and more
      modern methods were used for causal inference-namely, propensity score and
      marginal structural models (MSMs), which have not been used before in studies of
      cancer survival and Chinese herbal medicine. PAM+V combined with conventional
      therapy, compared with conventional therapy alone, reduced the risk of death in
      stage I by 95%, stage II by 64%, stage III by 29%, and stage IV by 75%. There was
      no significant difference between short-term and long-term PAM+V. Combining PAM+V
      with conventional therapy improved survival, compared with conventional therapy
      alone, suggesting that prospective trials combining PAM+V with conventional
      therapy are justified.

PMID- 21964513
TI  - Multilocus species tree analyses resolve the radiation of the widespread Bufo
      bufo species group (Anura, Bufonidae).
AB  - New analytical methods are improving our ability to reconstruct robust species
      trees from multilocus datasets, despite difficulties in phylogenetic
      reconstruction associated with recent, rapid divergence, incomplete lineage
      sorting and/or introgression. In this study, we applied these methods to resolve
      the radiation of toads in the Bufo bufo (Anura, Bufonidae) species group, ranging
      from the Iberian Peninsula and North Africa to Siberia, based on sequences from
      two mitochondrial and four nuclear DNA regions (3490 base pairs). We obtained a
      fully-resolved topology, with the recently described Bufo eichwaldi from the
      Talysh Mountains in south Azerbaijan and Iran as the sister taxon to a clade
      including: (1) north African, Iberian, and most French populations, referred
      herein to Bufo spinosus based on the implied inclusion of populations from its
      type locality and (2) a second clade, sister to B. spinosus, including two sister
      subclades: one with all samples of Bufo verrucosissimus from the Caucasus and
      another one with samples of B. bufo from northern France to Russia, including the
      Apennine and Balkan peninsulas and most of Anatolia. Coalescent-based estimations
      of time to most recent common ancestors for each species and selected subclades
      allowed historical reconstruction of the diversification of the species group in
      the context of Mediterranean paleogeography and indicated a long evolutionary
      history in this region. Finally, we used our data to delimit the ranges of the
      four species, particularly the more widespread and historically confused B.
      spinosus and B. bufo, and identify potential contact zones, some of which show
      striking parallels with other co-distributed species.

PMID- 21964515
TI  - Retracted article: Headaches and brain tumors.

PMID- 21964514
TI  - Charge transfer properties of Troger base derivatives.
AB  - Two triarylamine centers bridged through an aliphatic bridge feature unexpected
      charge transfer properties, bearing an important electronic coupling between them
      in the absence of a pi linker; EPR, electrochemistry, electronic spectroscopy and
      first principles molecular calculations are combined to study the electronic
      structure of this compound.

PMID- 21964516
TI  - Preimplantation genetic diagnosis of alpha-thalassemia-SEA using novel multiplex
      fluorescent PCR.
AB  - PURPOSE: Preimplantation genetic diagnosis (PGD) is an alternative to prenatal
      diagnosis (PND) giving couples at risk a chance to start a pregnancy with a
      disease-free baby. This study aimed to develop a new PGD protocol for alpha
      thalassemia(-SEA) mutation, the commonest Mendelian disorder. PATIENTS AND
      METHODS: Multiplex fluorescent PCR was employed for mutation, contamination and
      linkage analysis. A couple experienced termination of pregnancy following
      positive PND decided to join the project. RESULTS: Novel primers for alpha
      thalassemia(-SEA) mutation amplifying 5 DNA fragments were developed. Two PGD
      cycles were performed, resulting in an un-affected baby. PND confirmed the
      heterozygous result. From 24 embryos, 87.5% of affected genotype were of best
      quality compared to 0% and 18.2% of those with normal and heterozygous,
      respectively. CONCLUSIONS: A novel PCR protocol for the common alpha-thalassemia(
      SEA) mutation is reported. This test should be widely applicable. Interestingly,
      a potential effect of alpha-thalassemia(-SEA) mutation on preimplantation
      embryonic development was noticed.

PMID- 21964517
TI  - Contribution of cryopreservation in a mandatory SET policy: analysis of 5 years
      of application of law in an academic IVF center.
AB  - OBJECTIVE: To analyse treatment outcomes after SET law enforcement and to
      evaluate the contribution of cryopreservation in a SET policy. MATERIAL: Embryo
      transfer cycles performed after the law enforcement (SET period) was
      retrospectively compared to the cycles performed before the law enforcement (DET
      period). RESULTS: Pregnancy and delivery rates after fresh transfer of SET and
      DET periods were comparable (31.7% versus 33.3% and 24.5% versus 26.2%,
      respectively, NS). Overall twin delivery rate is significantly decreased after
      the law enforcement (11.3% versus 22.4%, p < 0.001) but not in patients aged 36
      to 39 years (20.3% versus 24%, NS). Frozen-thawed embryo cycles allowed similar
      cumulative pregnancy rate (30.6%, NS). Taking into account all frozen embryos
      still to be transferred, SET period offers a better overall pregnancy rate than
      the DET period (36.1% versus 32.3%, p < 0.01). CONCLUSIONS: The Belgian law
      allowed a dramatic reduction of twin deliveries especially for patients under 39
      years. Cryopreservation maintains a similar cumulative pregnancy rate.

PMID- 21964518
TI  - Sequence of the pearl oyster carbonic anhydrase-related protein and its
      evolutionary implications.
AB  - Carbonic anhydrases are conserved in vertebrates and invertebrates, and a
      noncatalytic carbonic anhydrase-related protein VIII (CARP VIII) has been found
      in deuterostomes and the phylum Placozoa. I isolated a cDNA encoding a
      noncatalytic CARP from the mantle of the pearl oyster Pinctada fucata. The
      polypeptide (CARP-1) predicted from the nucleotide sequence shares 44-60%
      identity with known CARP VIII sequences, and its phylogenetic analysis showed
      that P. fucata formed a single group with deuterostome invertebrates. However,
      since CARP VIII sequences are not identified in protostomes, these results
      suggest that CARP-1 may have originated in molluscs independently from
      deuterostome CARP VIII sequences.

PMID- 21964519
TI  - Camelus dromedarius putative cytochrome P450 enzyme CYP2E1: complete coding
      sequence and phylogenetic tree.
AB  - This study determined the full-length sequence of CYP2E1, one of six cytochrome
      P450 genes previously examined in camel tissues by western blotting and semi
      quantitative PCR. The Camelus dromedarius CYP2E1 has an open reading frame of
      1,473 bp, and the cDNA encodes a protein of 490 amino acid residues with a
      molecular weight of 54.8 kDa. The deduced amino acid sequence showed the highest
      identity with Bos taurus (88%), Sus scrofa (87%), and Homo sapiens (83%). In a
      phylogenetic analysis, the C. dromedarius CYP2E1 isoform was located beside
      cattle and pigs. The deduced amino acid sequence of camel CYP2E1 showed the
      conserved proline-rich amino terminus and the heme-binding signature localized
      near the carboxy terminus of the protein.

PMID- 21964520
TI  - Comparative genetics of the poly-Q tract of ataxin-1 and its binding protein PQBP
      1.
AB  - Human PQBP-1 is known to interact with triplet repeat disease gene products such
      as ataxin and huntingtin through their poly-glutamine (poly-Q) tracts. The poly-Q
      tracts show extensive variation in both the number and the configuration of
      repeats among species. A surface plasmon resonance assay showed clear interaction
      between human PQBP-1 and Q(11), representative of the poly-Q tract of the ataxin
      1 of Old World monkeys. No response was observed using Q(2)PQ(2)P(4)Q(2),
      representative of the poly-Q tract of the ataxin-1 of New World monkeys. This
      implies that the interaction of human PQBP-1 with ataxin-1 is limited to humans
      and closely related species. Comparison of the human and mouse PQBP-1 sequences
      showed an elevated amino acid substitution rate in the polar amino acid-rich
      domain of PQBP-1 that is responsible for binding to poly-Q tracts. This could
      have been advantageous to the new biological function of human PQBP-1 through
      poly-Q tracts.

PMID- 21964521
TI  - In vivo neurochemical evidence that newly synthesised GABA activates GABA(B), but
      not GABA(A), receptors on dopaminergic nerve endings in the nucleus accumbens of
      freely moving rats.
AB  - GABA released from accumbal GABAergic interneurons plays an inhibitory role in
      the regulation of dopamine efflux through GABA(B) and GABA(A) receptors located
      on accumbal dopaminergic nerve endings. The cytosolic newly synthesised GABA
      alters vesicular GABA levels and, accordingly, the amount of GABA released from
      the neuron. Therefore, we hypothesised that glutamic acid decarboxylase (GAD)
      which generates GABA in accumbal GABAergic neurons, at least partly determines
      the GABA receptor subtype-mediated GABAergic tonus. To (in)validate this
      hypothesis, in vivo microdialysis was used to study the effects of an intra
      accumbal infusion of the GAD inhibitor l-allylglycine (allylglycine) on the
      accumbal dopamine efflux of freely moving rats. The intra-accumbal infusion of
      allylglycine (50.0, 250.0 and 500.0 nmol) dose-dependently increased the accumbal
      dopamine levels. The co-administration of tetrodotoxin (720 pmol) suppressed the
      allylglycine (500.0 nmol)-induced dopamine efflux. The intra-accumbal infusion of
      GABA(B) receptor agonist baclofen (2.5 and 5.0 nmol) inhibited the allylglycine
      (500.0 nmol)-induced dopamine efflux. The baclofen's effects were counteracted by
      GABA(B) receptor antagonist saclofen (10.0 nmol). Neither GABA(A) receptor
      agonist (muscimol: 25.0 and 250.0 pmol) nor antagonist (bicuculline: 50.0 pmol)
      altered the allylglycine (250.0 and 500.0 nmol)-induced dopamine efflux. The
      present study provides in vivo neurochemical evidence that newly synthesised GABA
      that exerts an inhibitory tonus on the accumbal dopaminergic activity, acts at
      the level of GABA(B) receptors, but not GABA(A) receptors. The present study also
      shows that there is an allylglycine-insensitive GABA pool that release GABA
      exerting an inhibitory control of the accumbal dopaminergic activity, at the
      level of GABA(A) receptors. This article is part of a Special Issue entitled
      'Post-Traumatic Stress Disorder'.

PMID- 21964522
TI  - Maternal deprivation and dendritic complexity in the basolateral amygdala.
AB  - RATIONALE: Maternal deprivation at postnatal day 3 was reported to enhance fear
      learning in a sex specific manner. Since the amygdala is critically involved in
      fear conditioning we examined here whether maternal deprivation regulates
      dendritic complexity in this area. OBJECTIVE: To assess whether maternal
      deprivation regulates dendritic complexity in the basolateral amygdala of male
      and female rats. METHODS: Using the Golgi-impregnation method, we studied whether
      24 h of maternal deprivation on postnatal day 3 alters dendritic complexity of
      pyramidal and stellate cells in the basolateral amygdala of adult male and female
      rats. RESULTS: Maternal deprivation did not affect the total branch length,
      number of branch points and primary dendrites or dendritic complexity index in
      male and female offspring. CONCLUSION: Although a brief period of maternal
      deprivation increases fear conditioned responses, it did not affect dendritic
      complexity in the basolateral amygdala. This suggests that other cellular
      substrates for learning and memory, e.g. at synaptic or cellular level, underlie
      the enhanced expression of fear memories after exposure to early life stress.
      This article is part of a Special Issue entitled 'Anxiety and Depression'.

PMID- 21964523
TI  - Rapporteur's report on Session 3: Biology and mechanisms.

PMID- 21964524
TI  - Local SAR enhancements in anatomically correct children and adult models as a
      function of position within 1.5 T MR body coil.
AB  - Usage of magnetic resonance imaging (MRI) is continuously increasing due to its
      excellent soft-tissue contrast and improving diagnostic values. MRI also has the
      advantage that it operates without ionizing radiation. The main safety concerns
      are torque, acceleration by the static field, nerve stimulation by the gradient
      fields, and tissue heating by the radio-frequency (RF) fields. This paper
      investigates if children and fetuses are at higher risks than adults when the
      current RF regulations are applied. We analyzed and compared local absorption
      hotspots, i.e., the peak spatial specific absorption rate averaged over any 10 g
      (psSAR10g) for five adults, three children of ages 5, 11 and 14 years, and 1
      pregnant female (36 weeks' gestation) in 10 different Z-positions (head to
      calves). In the First Level Operating Mode (4 W/kg whole-body averaged exposure),
      the psSAR10g values found for adults were as large as 60 W/kg in the trunk and
      104 W/kg in the extremities. The corresponding values for children were 43 and 58
      W/kg, respectively, and 14 W/kg for the unborn child. Modeling of worst case
      anatomical RF loops can substantially increase the psSAR10g values, i.e., by
      factor >>2. The results suggest that local exposure for children and fetuses is
      smaller than for adults (15-75%), i.e., no special considerations for children
      and the unborn child are needed regarding psSAR10g due to RF. However, the local
      thermal load of the unborn may be significantly increased due to the high
      exposure average (up to 4 W/kg) of the non-perfused amniotic fluid.

PMID- 21964525
TI  - Epithelial-specific methylation marker: a potential plasma biomarker in advanced
      non-small cell lung cancer.
AB  - BACKGROUND: Under physiological conditions, leukocytes contribute the majority of
      circulating DNA in plasma. Therefore, detection of methylation at the SHP-1
      promoter 2 (SHP1P2) in plasma, which represents epithelial tumor-derived
      circulating nucleic acids, may serve as a potential noninvasive biomarker for non
      small cell lung cancer (NSCLC). MATERIALS AND METHOD: A quantitative polymerase
      chain reaction-based assay was used to determine the level of SHP1P2 methylation
      in plasma. Blood samples were prospectively collected from 58 patients with
      advanced NSCLC, 20 patients with early NSCLC, and 52 healthy volunteers. RESULTS:
      Most of the healthy volunteers exhibited undetectable levels of SHP1P2
      methylation. In contrast, the pretreatment levels of SHP1P2 methylation in the
      patients with NSCLC were readily detectable, with a median value of 770 pg ml(-1)
      (0-26,500 pg ml(-1)), which was significantly higher than that of the healthy
      controls. Furthermore, the patients with advanced NSCLC who presented baseline
      levels of SHP1P2 methylation of less than 700 pg ml(-1) exhibited enhanced median
      progression-free survival (5.2 versus 2.6 months, p = 0.009) and improved median
      overall survival (12.6 versus 7.6 months, p = 0.01) compared with patients who
      exhibited SHP1P2 methylation levels greater than 700 pg ml(-1). From a
      multivariate analysis, the levels of SHP1P2 methylation were significantly
      associated with survival rates in advanced NSCLC. CONCLUSION: Measurement of the
      level of SHP1P2 methylation in plasma serves as a potential noninvasive biomarker
      for the prognostic assessment of patients with lung cancer. This biomarker can be
      used to develop risk-adaptive treatments for patients with lung cancer.

PMID- 21964526
TI  - Serum heparan sulfate concentration is correlated with the failure of epidermal
      growth factor receptor tyrosine kinase inhibitor treatment in patients with lung
      adenocarcinoma.
AB  - INTRODUCTION: The epidermal growth factor receptor (EGFR) mutation status is a
      validated biomarker for the stratification of EGFR-tyrosine kinase inhibitor
      (EGFR-TKIs) treatment in patients with non-small cell lung cancer (NSCLC);
      however, its use is limited in patients with wild-type EGFR, and new biomarkers
      are needed. We hypothesized that the serum concentration of heparan sulfate (HS),
      which activates oncogenic growth factor receptor signaling through EGFR and non
      EGFR signaling pathways, may be a novel glycobiological biomarker for EGFR-TKIs
      treatment in NSCLC. METHODS: The pretreatment serum HS concentrations were
      determined using enzyme-linked immunosorbent assay in 83 patients with stage IV
      non-small cell lung adenocarcinoma who received EGFR-TKIs treatment. The
      relationship between the serum HS concentrations and patient characteristics,
      tumor response, progression-free survival (PFS), and overall survival (OS) were
      analyzed. RESULTS: Patient sex, performance status, smoking history, and EGFR
      mutation status were associated with tumor response. The serum HS concentrations
      were significantly higher among patients with progressive disease than among
      those without progressive disease (p = 0.003). Furthermore, the serum HS
      concentrations were strongly associated with a poor PFS and OS in a univariate
      Cox analysis (p = 0.0022 and p = 0.0003, respectively). A stratified multivariate
      Cox model according to the EGFR mutation status showed that higher HS
      concentrations were significantly associated with a shorter PFS and OS (p =
      0.0012 and p = 0.0003). CONCLUSION: We concluded that a high-serum HS
      concentration was strongly related to a poor treatment outcome of EGFR-TKIs and
      may be a promising noninvasive and repeatable glycobiological biomarker in cancer
      treatment.

PMID- 21964527
TI  - C609T polymorphism of NAD(P)H quinone oxidoreductase 1 as a predictive biomarker
      for response to amrubicin.
AB  - INTRODUCTION: Amrubicin is a promising agent in the treatment of lung cancer, but
      predictive biomarkers have not yet been described. NAD(P)H:quinone oxidoreductase
      1 (NQO1) is an enzyme known to metabolize amrubicinol, the active metabolite of
      amrubicin, to an inactive compound. We examined the relationship between NQO1 and
      amrubicinol cytotoxicity. METHODS: Gene and protein expression of NQO1,
      amrubicinol cytotoxicity, and C609T single-nucleotide polymorphism of NQO1 were
      evaluated in 29 lung cancer cell lines: 14 small cell lung cancer (SCLC) and 15
      non-SCLC (NSCLC). The involvement of NQO1 in amrubicinol cytotoxicity was
      evaluated by small interfering RNA against NQO1. RESULTS: A significant inverse
      relationship between both gene and protein expression of NQO1 and amrubicinol
      cytotoxicity was found in all cell lines. Treatment with NQO1 small interfering
      RNA increased amrubicinol cytotoxicity and decreased NQO1 expression in both
      NSCLC and SCLC cells. Furthermore, cell lines genotyped homozygous for the 609T
      allele showed significantly lower NQO1 protein expression and higher sensitivity
      for amrubicinol than those with the other genotypes in both NSCLC and SCLC cells.
      CONCLUSIONS: NQO1 expression is one of the major determinants for amrubicinol
      cytotoxicity, and C609T single-nucleotide polymorphism of NQO1 could be a
      predictive biomarker for response to amrubicin treatment.

PMID- 21964528
TI  - Implications of delayed initiation of radiotherapy: accelerated repopulation
      after induction chemotherapy for stage III non-small cell lung cancer.
AB  - INTRODUCTION: For patients with stage III non-small cell lung cancer treated with
      induction chemotherapy (ICT), delayed initiation of subsequent radiotherapy (RT)
      may allow for repopulation in the interval between treatment modalities and
      during the early phase of RT. We quantified the impact of postinduction RT timing
      by evaluating the pace of tumor regrowth. METHODS: Institutionally approved
      retrospective review identified 21 analyzable patients with stage III non-small
      cell lung cancer who had platinum-based ICT followed by RT+/- chemotherapy from
      2002 to 2009. Radiographic response was determined by RECIST criteria and the
      volume of the single largest tumor mass on the pre-ICT, post-ICT, and RT-planning
      computed tomography scans. RESULTS: After ICT, the median percent volume change
      from pre-ICT baseline was -41% (range -86 to +86%). By the RT-planning computed
      tomography scan, the median percent volume change from the post-ICT timepoint was
      +40% (range -11 to +311%) and the median volume change was +20 ml (range -4 to
      102 ml); these changes were significant (p = 0.0002). Similar results were seen
      for tumor diameter. A correlation was observed between the amount of delay and
      degree of regrowth for percent volume (p = 0.0006) and percent diameter change (p
      = 0.003). A delay greater than 21 days produced greater increases in percent
      volume change (p = 0.002) and percent diameter (p = 0.055) than lesser delays.
      CONCLUSIONS: After ICT, tumor regrowth can occur within a few weeks. Radiation
      treatment planning should begin as soon as possible after the administration of
      ICT to maximize the benefits of cytoreduction.

PMID- 21964529
TI  - Prognostic impact of number of resected and involved lymph nodes at complete
      resection on survival in non-small cell lung cancer.
AB  - BACKGROUND: Lymph node (LN) status is a major determinant of stage and survival
      in patients with lung cancer. In the 7th edition of the TNM Classification of
      Malignant Tumors, the number of involved LNs is included in the definition of pN
      factors in breast, stomach, esophageal, and colorectal cancer, and the pN status
      significantly correlates with prognosis. METHODS: We retrospectively investigated
      the prognostic impact of the number of resected LNs (RLNs) and involved LNs in
      the context of other established clinical prognostic factors, in a series of 928
      consecutive patients with non-small cell lung cancer (NSCLC) who underwent
      complete resection at our institution between 2000 and 2007. RESULTS: The mean
      number of RLNs was 15. There was a significant difference in the total number of
      RLNs categorized between less than 10 and >=10 (p = 0.0129). Although the
      incidence of LN involvement was statistically associated with poor prognosis, the
      largest statistically significant increase in overall survival was observed
      between 0 to 3 and >=4 involved LNs (hazard ratio = 7.680; 95% confidence
      interval = 5.051-11.655, p < 0.0001). On multivariate analysis, we used the ratio
      between the number of involved LNs and RLNs. The number of RLNs was found to be a
      strong independent prognostic factor for NSCLC (hazard ratio = 6.803; 95%
      confidence interval = 4.137-11.186, p < 0.0001). CONCLUSION: Complete resection
      including 10 or more LNs influenced survival at complete NSCLC resection. Four
      involved LNs seemed to be a benchmark for NSCLC prognosis. The number of involved
      LNs is a strong independent prognostic factor in NSCLC, and the results of this
      study may provide new information for determining the N category in the next
      tumor, node, metastasis classification.

PMID- 21964530
TI  - Serum vascular endothelial growth factor and COX-2/5-LOX inhibition in advanced
      non-small cell lung cancer: Cancer and Leukemia Group B 150304.
AB  - INTRODUCTION: Eicosanoids, including PGE-2 and 5-HETE, can increase levels of
      plasma vascular endothelial growth factor (VEGF). Overexpression of COX-2 or 5
      LOX increases levels of PGE-2 and 5-HETE, respectively. Elevated levels of VEGF
      are common in patients with non-small cell lung cancer (NSCLC). We prospectively
      measured VEGF in serum collected from patients enrolled in Cancer and Leukemia
      Group B 30203, a randomized phase II study of eicosanoid modulation in addition
      to chemotherapy in patients with advanced NSCLC, to determine whether these
      levels had prognostic significance and whether they correlated with COX-2
      expression and/or responded to inhibition of COX-2 or 5-LOX. METHODS: Pre- and
      post-treatment serum was collected from patients enrolled in CALGB 30203. Serum
      VEGF levels were determined using enzyme-linked immunosorbent assay methodology.
      Statistical analyses were performed to determine the correlation between
      pretreatment serum VEGF levels and time of overall survival. Pretreatment
      formalin fixed tissue was stained for 5-LOX and COX-2 by immunohistochemistry.
      RESULTS: The median baseline VEGF level was 502 pg/ml (range, 55-3453 pg/ml).
      Dichotomized serum VEGF levels at median inversely correlated with survival time
      (p = 0.008), as did VEGF levels as a continuous variable in multivariate analysis
      (p = 0.035). VEGF levels were significantly correlated neither with baseline COX
      2 expression (Pearson r = 0.1524, p = 0.271) nor with 5-LOX expression. Treatment
      with COX-2 or 5-LOX inhibitors did not alter the levels. CONCLUSION: These data
      indicate that elevated serum VEGF is a negative prognostic variable in NSCLC.
      VEGF levels are neither correlated with baseline tumor COX-2 expression nor do
      they respond to COX-2 and/or 5-LOX inhibition plus chemotherapy.

PMID- 21964531
TI  - Prolonged survival in patients with lung cancer with diabetes mellitus.
AB  - INTRODUCTION: Patients with lung cancer have a high frequency of comorbidity.
      Data on the impact of diabetes mellitus, the most frequent endocrine disorder, on
      the prognosis of lung cancer are conflicting. The aim was to investigate the
      impact of diabetes mellitus on survival in lung cancer. METHOD: We analyzed data
      from a cohort, the Nord-Trondelag Health Study (HUNT study) linked to the
      Norwegian Cancer Registry and controlled the results using two lung cancer
      studies, the Pemetrexed Gemcitabine study and the Norwegian Lung Cancer Biobank.
      Survival in lung cancer with and without diabetes mellitus was compared using the
      Kaplan-Meier method and Cox regression model for each study and the studies
      combined. RESULTS: One thousand six hundred seventy-seven cases of lung cancer
      were included, 1031 from HUNT study, 436 from the Pemetrexed Gemcitabine study,
      and 210 from the Norwegian Lung Cancer Biobank registry, and among these 77
      patients had diabetes mellitus. In the combined analysis, patients with lung
      cancer with diabetes mellitus had increased survival compared with those without
      (p = 0.005). The 1-, 2-, and 3-year survival in patients with lung cancer with
      and without diabetes mellitus were 43% versus 28%, 19% versus 11%, and 3% versus
      1%, respectively. Adjusting for age, gender, histology, and stage of disease in
      the Cox regression model, the hazard ratio for survival in patients with lung
      cancer with diabetes mellitus was 0.55 (95% CI, 0.41-0.75) as compared with
      without. CONCLUSION: Patients with lung cancer with diabetes mellitus have an
      increased survival compared with those without diabetes mellitus.

PMID- 21964532
TI  - Identifying inhibitors of epithelial-mesenchymal transition by connectivity map
      based systems approach.
AB  - BACKGROUND: Acquisition of mesenchymal phenotype by epithelial cells by means of
      epithelial-mesenchymal transition (EMT) is considered as an early event in the
      multistep process of tumor metastasis. Therefore, inhibition of EMT might be a
      rational strategy to prevent metastasis. METHODS: Using the global gene
      expression profile from a cell culture model of transforming growth factor-beta
      (TGF-beta)-induced EMT, we identified potential EMT inhibitors. We used a
      publicly available database (www.broad.mit.edu/cmap) comprising gene expression
      profiles obtained from multiple different cell lines in response to various drugs
      to derive negative correlations to EMT gene expression profile using Connectivity
      Map, a pattern matching tool. RESULTS: Experimental validation of the identified
      compounds showed rapamycin as a novel inhibitor of TGF-beta signaling along with
      17-AAG, a known modulator of TGF-beta pathway. Both of these compounds completely
      blocked EMT and the associated migratory and invasive phenotype. The other
      identified compound, LY294002, demonstrated a selective inhibition of mesenchymal
      markers, cell migration and invasion, without affecting the loss of E-cadherin
      expression or Smad phosphorylation. CONCLUSIONS: Our data reveal that rapamycin
      is a novel modulator of TGF-beta signaling, and along with 17-AAG and LY294002,
      could be used as therapeutic agent for inhibiting EMT. This study demonstrates
      the potential of a systems approach in identifying novel modulators of a complex
      biological process.

PMID- 21964533
TI  - Phase II study of cediranib in patients with malignant pleural mesothelioma: SWOG
      S0509.
AB  - INTRODUCTION: Malignant pleural mesothelioma (MPM) tumors express vascular
      epithelial growth factor (VEGF) and VEGF receptors. We conducted a phase II study
      of the oral pan-VEGF receptor tyrosine kinase inhibitor, cediranib, in patients
      with MPM after platinum-based systemic chemotherapy. METHODS: Patients with MPM
      previously treated with a platinum-containing chemotherapy regimen and a
      performance status 0 to 2 were eligible for enrollment. Cediranib 45 mg/d was
      administered until progression or unacceptable toxicity. The primary end point
      was response rate. Tumor measurements were made by RECIST criteria, with a subset
      analysis conducted using modified RECIST. A two-stage design with an early
      stopping rule based on response rate was used. RESULTS: Fifty-four patients were
      enrolled. Of 47 evaluable patients, 4 patients (9%) had objective responses, 16
      patients (34%) had stable disease, 20 patients (43%) had disease progression, 2
      patients (4%) had symptomatic deterioration, and 1 patient (2%) had early death.
      The most common toxicities were fatigue (64%), diarrhea (64%), and hypertension
      (70%); 91% of patients required a dose reduction. Median overall survival was 9.5
      months, 1-year survival was 36%, and median progression-free survival was 2.6
      months. CONCLUSION: Cediranib monotherapy has modest single-agent activity in MPM
      after platinum-based therapy. However, some patient tumors were highly sensitive
      to cediranib. This study provides a rationale for further testing of cediranib
      plus chemotherapy in MPM and highlights the need to identify a predictive
      biomarker for cediranib.

PMID- 21964534
TI  - Changes in plasma mass-spectral profile in course of treatment of non-small cell
      lung cancer patients with epidermal growth factor receptor tyrosine kinase
      inhibitors.
AB  - INTRODUCTION: Our previous study showed that pretreatment serum or plasma Matrix
      Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry may predict
      clinical outcome of non-small cell lung cancer (NSCLC) patients treated with
      epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). In
      this study, plasma proteomic profiles of NSCLC patients were evaluated in the
      course of EGFR TKIs therapy. MATERIALS AND METHODS: Plasma samples were collected
      at baseline, in the course of gefitinib therapy and at treatment withdrawal.
      Samples were analyzed by Matrix-Assisted Laser Desorption/Ionization Time-of
      Flight Mass Spectrometry. Acquired spectra were classified by the VeriStrat test
      into "good" and "poor" profiles. The association between VeriStrat classification
      and progression-free survival (PFS) and overall survival (OS), and types of
      clinical progression, was analyzed. RESULTS: Plasma samples from 111 NSCLC
      patients treated with gefitinib were processed. VeriStrat "good" classification
      at baseline correlated with longer PFS (hazard ratio [HR], 0.54; 95% confidence
      interval, 0.35-0.83; p = 0.005) and OS (HR, 0.40; 95% confidence interval, 0.26
      0.61; p < 0.0001), when compared with VeriStrat "poor." Multivariate analysis
      confirmed longer PFS (HR, 0.52; p = 0.025) and OS (HR, 0.44; p = 0.001) in
      patients classified as VeriStrat "good", when VeriStrat was considered as a time
      dependent variable. About one-third of baseline "good" classifications had
      changed to "poor" at the time of treatment withdrawal; progression in these
      patients was associated with the development of new lesions. CONCLUSIONS: Our
      findings support the role of VeriStrat in the assistance in treatment selection
      of NSCLC patients for EGFR TKI therapy and its potential utility in treatment
      monitoring.

PMID- 21964535
TI  - Associations between changes in quality of life and survival after lung cancer
      surgery.
AB  - INTRODUCTION: The aim of this study was to analyze the association between
      changes in quality of life and survival after lung cancer surgery. METHODS: In a
      prospective population-based cohort study, quality of life was estimated using
      the Medical Outcomes Study 36-Item Short Form (SF-36) questionnaire before and 6
      months after lung cancer surgery. Cox regression models adjusting for potential
      confounding factors were used to analyze the association between baseline SF-36
      scores and changes in SF-36 scores and survival. RESULTS: A SF-36 questionnaire
      was distributed to 249 patients at baseline. We excluded 79 patients with
      histopathology other than primary lung cancer. Six months after surgery, 11
      patients died and 18 patients did not return the questionnaire, leaving 141
      patients with data from both baseline and follow-up. The baseline SF-36 physical
      component summary score was significantly associated with survival, but the
      baseline mental component was not. Declines of 10% in the physical and mental
      component summary scores from baseline to follow-up were associated with an 18
      and 13% higher risk of death, respectively. CONCLUSIONS: Changes in quality of
      life during 6 months after surgery for lung cancer may provide prognostic
      information regarding survival.

PMID- 21964536
TI  - Matrix metalloproteinase-9 as new biomarkers of severity in multiple organ
      dysfunction syndrome caused by trauma and infection.
AB  - Multiple organ dysfunction syndrome (MODS) is an important cause of morbidity and
      mortality in intensive care unit. A severe insult in the form of infection or
      trauma primes the host immune system so that a subsequent, relatively trivial
      insult produces systemic inflammation response syndrome, which can lead to MODS
      and death. Matrix metalloproteinase-9 (MMP-9) is stored in the tertiary granules
      of polymorphonuclear leukocytes. These cells are key effectors in acute
      inflammatory diseases, such as sepsis and MODS. Endotoxin leads to rapid release
      of MMP-9 from these granules in vitro and in vivo. However, the role of this
      enzyme in MODS, and whether it is associated with organ injury at the early stage
      of MODS remains unclear. This present work may study role of MMP-9 with the MODS
      rats that caused by trauma and infection and investigate the mechanism of organ
      injury at the early stage of MODS. Here, we developed a rat model for MODS caused
      by trauma and infection and analyzed the dynamic level of MMP-9 and determined
      the relationship between MMP-9 level and early phase of organ injury in MODS rat.
      The histological changes in pulmonary, renal, and hepatic tissue were observed by
      light microscope. The expressions of plasma MMP-9 proteins were detected by an
      enzyme linked immunosorbent assay and its levels in the pulmonary, renal, and
      hepatic tissue were detected by using immunohistochemistry, respectively. The
      results indicated that there were no significant improvements in histopathology
      of rats in control group. However, the pulmonary, renal, and hepatic damage were
      serious in MODS groups. The concentration of MMP-9 in plasma and tissues of MODS
      rats increased markedly at the early stage and were higher than that of the
      control group. Moreover, the MMP-9 level in plasma positively correlated with the
      levels of pulmonary, renal, and hepatic tissue. This study clearly shows that MMP
      9 is good biomarker to predict the severity of injury organ at the early phase of
      MODS.

PMID- 21964537
TI  - Microarray expression analysis in delayed cardioprotection: the effect of
      exercise, AICAR, or metformin and the possible role of AMP-activated protein
      kinase (AMPK).
AB  - AMP-activated protein kinase (AMPK) is an enzyme which may be involved in
      cardioprotective mechanisms in the ischemic heart. Exercise, AICAR, and
      metformin, all known activators of AMPK, induce delayed cardioprotection which
      protects the heart against ischemia-reperfusion injury. The objective was to
      determine the effect of exercise, AICAR, and metformin on gene expression profile
      and to demonstrate possible interactions in different genes and functions. Rats
      were divided into either an exercise, AICAR, metformin, or control group. 3, 12,
      and 24 h after either a single bout of exercise training, a single injection of
      AICAR or a single dose of metformin, hearts were removed and gene expression
      profiles were analyzed in tissue from the left ventricle using Affymetrix gene
      chip probe arrays. Ingenuity Pathway Analysis (IPA) tool was used to analyze the
      regulated genes for relevant functions and diseases. Each gene chip identified up
      to 30,000 different probesets of which Ingenuity identified approximately up to
      12,000 genes. A total of 147, 304, and 114 different genes in the left ventricle
      whose expressions were altered >2.0-fold were identified in the exercise, AICAR,
      and metformin group, respectively. Seventy eight different genes were overlapping
      the exercise and AICAR group at 24 h. Ingenuity identified six overlapping genes
      between the exercise, AICAR, and metformin groups including NR4A3, TNFRSF12A,
      HBB, PENK, PAP, and MAP4K4. IPA software revealed an overabundance of focus
      molecules in all three intervention groups involving functions related to cell
      death, cellular growth and proliferation, gene expression and cancer. Exercise,
      AICAR, and metformin regulate several genes in the rat myocardium with the
      majority of overlapping genes observed in the exercise and AICAR group. Changes
      in gene programming mainly involved inflammatory and opioid systems recognized as
      cardioprotective pathways. Some of these genes may represent possible candidate
      genes involved in the molecular mechanisms of AMPK-induced delayed PC.

PMID- 21964538
TI  - 9-phenyl acridine exhibits antitumour activity by inducing apoptosis in A375
      cells.
AB  - Several acridine derivatives have been screened for their therapeutic potential
      and some are already established as antiprotozoan, antibacterial or anticancer
      agents. However, phenyl derivative at C-9 position of acridine had remained
      unexplored for their biological activity so far. In this report, we present our
      findings with 9-phenyl acridine (ACPH) as an anticancer agent. Both A375 and
      HeLa, two human cancer cell lines, were more sensitive to ACPH than normal cells
      namely human lymphocytes and also Chinese hamster V79 cells. ACPH also led to
      regression of tumour volume in mice. In A375 cells, we have shown that it caused
      DNA damage and blocked cell cycle progression at G(2)-M phase. Treatment with
      ACPH led to lowering of mitochondrial potential, upregulation of bax, release of
      cytochrome C and activation of caspase 3. As a new agent showing lower toxicity
      to normal cells and greater sensitivity towards cancerous cell line, ACPH shows
      promise as an effective cancer chemotherapeutic agent. ACPH treatment resulted in
      apoptotic death of cells through mitochondria-mediated caspase-dependent pathway.

PMID- 21964540
TI  - Catalase-like activity of human methemoglobin: a kinetic and mechanistic study.
AB  - Hydrogen peroxide triggers a redox cycle between methemoglobin and
      ferrylhemoglobin, leading to protein inactivation and oxygen evolution. In the
      present paper, the catalase-like oxygen production by human methemoglobin in the
      presence of H(2)O(2) was kinetically characterized with a Clark-type electrode.
      Progress curves showed a pseudo-steady state in the first minutes of the
      reaction, while double-reciprocal plots were upwardly concave, indicating
      positive co-operativity dependent upon protein concentration, which is a very
      unusual kinetic behavior. Addition of superoxide radical scavengers slightly
      increased activity, suggesting that most oxygen was produced biocatalytically. By
      considering all the experimental data obtained, a possible mechanism was
      proposed, including: (a) competition between the one-electron and the two
      electron reductions of the oxoferryl free radical species of hemoglobin, giving
      rise to ferrylhemoglobin and methemoglobin, respectively; (b) competition between
      the superoxide-dependent inactivation of the protein and its reduction back to
      the met state. Computer simulations of that model have been performed by
      numerically integrating the differential equations set describing the mechanism,
      which was seen to yield predictions of the kinetic parameters variation
      consistently with the kinetic behavior experimentally observed. We suggest that
      the catalase-like activity of methemoglobin must predominantly be a biocatalytic
      reaction that protects the protein against H(2)O(2)-induced suicide inactivation.

PMID- 21964539
TI  - Regulation and rate limiting mechanisms of Ca2+ ATPase (SERCA2) expression in
      cardiac myocytes.
AB  - Involvement of the calcineurin/NFAT pathway in transcription of cardiac
      sarcoplasmic reticulum Ca(2+) ATPase (SERCA2) was demonstrated (Prasad and Inesi,
      Am J Physiol Heart Circ Physiol 300(1):H173-H180, 2011) by upregulation of SERCA2
      following calcineurin (CN) activation by cytosolic Ca(2+), and downregulation of
      SERCA2 following CN inhibition with cyclosporine (CsA) or CN subunits gene
      silencing. We show here that in cultured cardiac myocytes, competitive engagement
      of the CN/NFAT pathway is accompanied by downregulation of SERCA2 and Ca(2+)
      signaling alterations. In fact, SERCA2 downregulation occurs following infection
      of myocytes with adenovirus vectors carrying luciferase or SERCA1 cDNA under
      control of NFAT-dependent promoters, but not under control of CMV promoters that
      do not depend on NFAT. SERCA2 downregulation is demonstrated by comparison with
      endogenous transcription and protein expression standards such as GAPDH and
      actin, indicating prominent SERCA2 involvement by the CN/NFAT pathway.
      Transcription of genes involved in hypertrophy, triggered by adrenergic agonist
      or by direct protein kinase C (PKC) activation with phorbol 12-myristate 13
      acetate (PMA), is also prominently dependent on CN/NFAT. This is demonstrated by
      CN inhibition with CsA, CN subunits gene silencing with siRNA, displacement of
      NFAT from CN with 9,10-Dihydro-9,10[1',2']-benzenoanthracene-1,4-dione (INCA-6),
      and myocyte infection with vectors carrying luciferase cDNA under control of NFAT
      dependent promoter. We show here that competitive engagement of the CN/NFAT
      pathway by endogenous genes involved in hypertrophy produces downregulation of
      SERCA2, reduction of Ca(2+) transport and inadequate Ca(2+) signaling. It is most
      interesting that, in the presence of adrenergic agonist, specific protein kinase
      C (PKC) inhibition with 3-[1-[3-(dimethylamino)propyl]-5-methoxy-1H-indol-3-yl]-4
      (1H-indol-3-yl)-1H-pyrrole-2,5-dione (Go 6983) prevents development of
      hypertrophy and maintains adequate SERCA2 levels and Ca(2+) signaling.

PMID- 21964541
TI  - Association of a matrix metallopeptidase 1 gene polymorphism with long-term
      outcome of thoracic aortic aneurysm.
AB  - Although genetic variants are thought to contribute to the development of
      thoracic aortic aneurysm including dissection (TAA), it remains unclear whether
      gene polymorphisms are associated with the long-term outcome of TAA. The purpose
      of the present study was to identify genetic variants associated with the long
      term outcome of medically treated patients with TAA. A total of 103 medically
      treated patients with TAA (13 aneurysms and 90 dissections) were retrospectively
      studied for their outcomes (mean follow-up period, 24 months). The genotypes for
      95 polymorphisms of 89 candidate genes were determined by a method that combines
      the polymerase chain reaction and sequence-specific oligonucleotide probes with
      suspension array technology. Evaluation of genotype distributions by the Chi
      square test and subsequent multivariable logistic regression analysis with
      adjustment for covariates revealed that the -340A->G polymorphism (rs514921) of
      the matrix metallopeptidase 1 gene (MMP1) was significantly (P=0.0288) associated
      with the outcome of TAA, with the minor G allele being related to a favorable
      outcome. The aneurysm diameter was significantly (P=0.0167) smaller in the
      combined group of the AG and GG genotypes for this polymorphism than in subjects
      with the AA genotype. Kaplan-Meier survival curves constructed according to MMP1
      genotypes showed a more favorable outcome of TAA (log-rank P=0.0146) in subjects
      with the G allele of rs514921. Determination of genotype for this polymorphism
      may prove informative for assessment of the long-term outcome of TAA.

PMID- 21964543
TI  - NMR, DFT and luminescence studies of the complexation of Zn(II) with 8
      hydroxyquinoline-5-sulfonate.
AB  - Multinuclear ((1)H, (13)C) magnetic resonance spectroscopy, DFT calculations and
      luminescence techniques have been used to study 8-hydroxyquinoline-5-sulfonate (8
      HQS) and its complexes with Zn(ii), in aqueous solution. The study combines the
      high sensitivity of luminescence techniques, the selectivity of multinuclear NMR
      spectroscopy with the structural details accessible through DFT calculations, and
      aims to obtain a detailed understanding of the complexation between the Zn(2+)
      ion and 8-HQS. In addition to a complete assignment of the (1)H and (13)C NMR
      signals of 8-HQS, a full speciation study has been performed. Over the
      concentration region studied, Zn(2+) metal ion forms only one significant complex
      species with 8-HQS in aqueous solution in the pH range 6-8. Job's method shows
      that this species has a 1:2 (metal:ligand) stoichiometry. The geometry around the
      metal centre, according to structural optimization using DFT calculations, is
      suggested to be square bipyramidal, with two coordinated water molecules mutually
      trans, and the remaining positions occupied by the donor groups of the two
      coordinated 8-HQS ligands. On binding to Zn(ii), 8-HQS shows a marked
      fluorescence compared with the weakly-luminescent free ligand. In addition, as
      previously noted, there are marked changes in the absorption spectra, which
      support the use of 8-HQS as a sensitive fluorescent sensor to detect Zn(2+) metal
      ion in surface waters, biological fluids, etc. Based on results of the structural
      studies, suggestions are made of ways for enhancing fluorescence sensitivity.

PMID- 21964542
TI  - Expression of NMDA receptor and its effect on cell proliferation in the
      subventricular zone of neonatal rat brain.
AB  - We investigated the involvement of N-methyl D-aspartate receptor (NMDAR) in
      neurogenesis of rat's subventricular zone (SVZ). For this purpose, we determined
      expression of the NMDAR subunits NR1, NR2A, and NR2B in SVZ of the neonatal
      Sprague-Dawley rats using immunohistochemical techniques. All three NMDAR
      subunits were expressed during postnatal day (PND)-1 to PND-28 whereas each
      subunit showed a distinct expression pattern. We also examined the functional
      effect of this receptor on cell proliferation in this region and, in this regard,
      the animals received either intraperitoneal injection of NMDAR agonist NMDA (2
      mg/kg/day) or selective non-competitive NMDAR antagonist MK-801 (10 mg/kg) or
      NR2B antagonist Ro25-6981 (40 mg/kg), respectively, at PND-3. A significant
      developmental increase of the total cell density was observed at PND-7 (P < 0.05)
      while proliferating cell nuclear antigen-positive cell density was significantly
      increased at PND-14 (P < 0.05) and at PND-28 (P < 0.05) in the SVZ after NMDA (2
      mg/kg/day) injection. Our data show that the NMDAR activation promoted the cell
      proliferation in SVZ during the neonatal period. We, therefore, inferred that
      NMDAR is expressed in SVZ of the neonatal rat brain and can promote neurogenesis,
      as through cell proliferation process in that region, and can thus be used as a
      potential therapeutic target in neurodegenerative diseases.

PMID- 21964544
TI  - Elusive cause of hypomagnesaemia.

PMID- 21964546
TI  - Electronic cigarettes as a method of tobacco control.

PMID- 21964545
TI  - Dyspepsia.

PMID- 21964547
TI  - Southall is cleared of serious professional conduct.

PMID- 21964548
TI  - Florida execution using pentobarbital goes ahead despite protests.

PMID- 21964549
TI  - Structural elucidation of main ozonation products of the artificial sweeteners
      cyclamate and acesulfame.
AB  - PURPOSE: The two artificial sweeteners cyclamate (CYC) and acesulfame (ACE) have
      been detected in wastewater and drinking water treatment plants. As in both
      facilities ozonation might be applied, it is important to find out if undesired
      oxidation products (OPs) are formed. METHODS: For the separation and detection of
      the OPs, several analytical techniques, including nuclear magnetic resonance
      experiments, were applied. In order to distinguish between direct ozone reaction
      and a radical mechanism, experiments were carried out at different pH values with
      and without scavenging OH radicals. Kinetic experiments were used for
      confirmation that the OPs are formed during short ozone contact time applied in
      waterworks. Samples from a waterworks using bank filtrate as raw water were
      analyzed in order to prove that the identified OPs are formed in real and full
      scale ozone applications. RESULTS: In the case of CYC, oxidation mainly occurs at
      the carbon atom, where the sulfonamide moiety is bound to the cyclohexyl ring.
      Consequently, amidosulfonic acid and cyclohexanone are formed as main OPs of CYC.
      When ozone reacts at another carbon atom of the ring a keto moiety is introduced
      into the CYC molecule. Acetic acid and the product ACE OP170, an anionic compound
      with m/z=170 and an aldehyde hydrate moiety, were identified as the main OPs for
      ACE. The observed reaction products suggest an ozone reaction according to the
      Criegee mechanism due to the presence of a C=C double bond. ACE OP170 was also
      detected after the ozonation unit of a full-scale drinking water treatment plant
      which uses surface water-influenced bank filtrate as raw water. CONCLUSIONS:
      Acesulfame can be expected to be found in anthropogenic-influenced raw water used
      for drinking water production. However, when ACE OP170 is formed during
      ozonation, it is not expected to cause any problem for drinking water suppliers,
      because the primary findings suggest its removal in subsequent treatment steps,
      such as activated carbon filters.

PMID- 21964550
TI  - Effect of Pb toxicity on leaf growth, antioxidant enzyme activities, and
      photosynthesis in cuttings and seedlings of Jatropha curcas L.
AB  - BACKGROUND: Cuttings and seedlings of Jatropha curcas L. were exposed to
      different regimes of lead (Pb) stress as Pb(NO3)2 at 0 (CK), 0.5, 1, 2, 3, and 4
      mM kg-1 soil. OBJECTIVES: The effect of Pb treatment on the root length,
      tolerance index, photosynthetic pigments, photosynthetic activity, lipid
      peroxidation, and antioxidant enzyme was studied in a greenhouse pot experiment.
      RESULTS: The results showed that root lengths and tolerance index decreased with
      increase of Pb concentration, but tolerance index of cuttings was always lower
      than those of the seedlings. For cuttings, Pb treatment had a stimulating effect
      on chlorophyll content, carotenoid content, and superoxide dismutase (SOD)
      activity at low concentration and an inhibitory effect at higher concentration.
      For seedlings, SOD activity increased with increasing Pb concentration. In both
      seedlings and cuttings, Pb caused inhibition of leaf growth and photosynthesis,
      and induced the membrane damage which was more obvious in the cuttings. In
      comparison with the control, the dynamic tendency of catalase and perxidase
      activities in the leaves of Pb-stressed plants all ascended, and then declined.
      DISCUSSION: The increase in enzyme activities demonstrated that seedlings were
      more tolerant to Pb stress than cuttings. These results also indicate that the
      antioxidant system may play an important role in eliminating or alleviating the
      toxicity of Pb in J. curcas seedlings and cuttings. The accumulation of Pb
      increased in a concentration-dependent manner; however, its translocation from
      root to shoot was low. The cuttings accumulated significantly higher Pb in roots
      than seedlings.

PMID- 21964551
TI  - Influence of adhesion on aerobic biodegradation and bioremediation of liquid
      hydrocarbons.
AB  - Biodegradation of poorly water-soluble liquid hydrocarbons is often limited by
      low availability of the substrate to microbes. Adhesion of microorganisms to an
      oil-water interface can enhance this availability, whereas detaching cells from
      the interface can reduce the rate of biodegradation. The capability of microbes
      to adhere to the interface is not limited to hydrocarbon degraders, nor is it the
      only mechanism to enable rapid uptake of hydrocarbons, but it represents a common
      strategy. This review of the literature indicates that microbial adhesion can
      benefit growth on and biodegradation of very poorly water-soluble hydrocarbons
      such as n-alkanes and large polycyclic aromatic hydrocarbons dissolved in a non
      aqueous phase. Adhesion is particularly important when the hydrocarbons are not
      emulsified, giving limited interfacial area between the two liquid phases. When
      mixed communities are involved in biodegradation, the ability of cells to adhere
      to the interface can enable selective growth and enhance bioremediation with
      time. The critical challenge in understanding the relationship between growth
      rate and biodegradation rate for adherent bacteria is to accurately measure and
      observe the population that resides at the interface of the hydrocarbon phase.

PMID- 21964553
TI  - Enhanced delivery of rapamycin by V156K-apoA-I high-density lipoprotein inhibits
      cellular proatherogenic effects and senescence and promotes tissue regeneration.
AB  - Although rapamycin (rapa) is a fungicide, it is now believed to possess the
      capacity to extend mammalian life span. Because rapamycin is insoluble in water,
      its study in the aqueous phase has been limited. We therefore solubilized
      rapamycin in isotonic buffer using reconstituted high-density lipoprotein
      containing V156K-apolipoprotein A-I (V156K-rHDL). Rapamycin (final concentration,
      0.1 mg/mL) was solubilized in rHDL containing either wild-type (WT) or V156K-apoA
      I (1 mg/mL of protein) prepared using the sodium cholate dialysis method. V156K
      rHDL containing rapamycin (V156K-rapa-rHDL) had a slightly larger particle size
      than rapamycin-loaded WT-rHDL (WT-rapa-rHDL). V156K-rapa-rHDL exhibited enhanced
      antioxidant ability, cholesteryl ester transfer protein inhibitory activity, and
      anti-atherosclerotic activity. Treatment with V156K-rapa-rHDL resulted in
      attenuation of senescence in human cells with increased cell survival and
      enhancement of tissue regenerative activities in zebrafish model compared with WT
      rapa-rHDL or rHDL alone.

PMID- 21964552
TI  - Beyond arousal and valence: the importance of the biological versus social
      relevance of emotional stimuli.
AB  - The present study addressed the hypothesis that emotional stimuli relevant to
      survival or reproduction (biologically emotional stimuli) automatically affect
      cognitive processing (e.g., attention, memory), while those relevant to social
      life (socially emotional stimuli) require elaborative processing to modulate
      attention and memory. Results of our behavioral studies showed that (1)
      biologically emotional images hold attention more strongly than do socially
      emotional images, (2) memory for biologically emotional images was enhanced even
      with limited cognitive resources, but (3) memory for socially emotional images
      was enhanced only when people had sufficient cognitive resources at encoding.
      Neither images' subjective arousal nor their valence modulated these patterns. A
      subsequent functional magnetic resonance imaging study revealed that biologically
      emotional images induced stronger activity in the visual cortex and greater
      functional connectivity between the amygdala and visual cortex than did socially
      emotional images. These results suggest that the interconnection between the
      amygdala and visual cortex supports enhanced attention allocation to biological
      stimuli. In contrast, socially emotional images evoked greater activity in the
      medial prefrontal cortex (MPFC) and yielded stronger functional connectivity
      between the amygdala and MPFC than did biological images. Thus, it appears that
      emotional processing of social stimuli involves elaborative processing requiring
      frontal lobe activity.

PMID- 21964554
TI  - The role of a surgical learning curve in urethral obstruction following
      autologous fascial sling: a case-series study.
AB  - INTRODUCTION AND HYPOTHESIS: Iatrogenic female urethral obstruction resulting
      from sling operations may be related to surgical inexperience and must be better
      understood. Although there are no widely recognized parameters for this type of
      study, a single-surgeon consecutive series offers an opportunity to study the
      role of expertise in sling operations over time. METHODS: This study
      consecutively examined 176 women who underwent an autologous fascial sling
      procedure. Postoperative urethral obstruction was identified by the occurrence of
      voiding dysfunctions. Clinically obstructed patients were invited to undergo a
      postoperative urodynamic evaluation after 3 months. To enable comparison,
      patients were placed into 6-month groups according to the time of surgery.
      RESULTS: A total of 159 cases were evaluated with a mean follow-up time of 32.4
      +/- 13.4 months. Stress continence was cured in 97.5% of cases. Although 29
      patients were identified as obstructed, only 20 underwent a postoperative
      urodynamic evaluation. Only five of the clinically obstructed cases showed a high
      P(det)Q(max). All of the other cases met one or more of the non-classic
      parameters linked to obstruction. Overactive bladder was present in 14 (63.6%) of
      the obstructed cases. Iatrogenic urethral obstruction was more common among the
      early cases (30.4%) than among the later ones (5%) (P < 0.001). Postoperative
      urodynamic evaluation showed a trend toward obstruction on pressure flow studies.
      CONCLUSIONS: Autologous fascial sling operations require expertise and involve a
      clear surgical learning curve. Iatrogenic obstruction in females does not fit a
      single model and may be difficult to recognize. Obstruction in females must be
      identified through clinical indicators and postoperative urinary complaints
      rather than the high detrusor pressure observed in men. Furthermore, iatrogenic
      female obstruction can probably be minimized but not eliminated.

PMID- 21964555
TI  - Study of the ST2 model of water close to the liquid-liquid critical point.
AB  - We perform successive umbrella sampling grand canonical Monte Carlo computer
      simulations of the original ST2 model of water in the vicinity of the proposed
      liquid-liquid critical point, at temperatures above and below the critical
      temperature. Our results support the previous work of Y. Liu, A. Z.
      Panagiotopoulos and P. G. Debenedetti [J. Chem. Phys., 2009, 131, 104508], who
      provided evidence for the existence and location of the critical point for ST2
      using the Ewald method to evaluate the long-range forces. Our results therefore
      demonstrate the robustness of the evidence for critical behavior with respect to
      the treatment of the electrostatic interactions. In addition, we verify that the
      liquid is equilibrated at all densities on the Monte Carlo time scale of our
      simulations, and also that there is no indication of crystal formation during our
      runs. These findings demonstrate that the processes of liquid-state relaxation
      and crystal nucleation are well separated in time. Therefore, the bimodal shape
      of the density of states, and hence the critical point itself, is a purely liquid
      state phenomenon that is distinct from the crystal-liquid transition.

PMID- 21964556
TI  - Prevalence of sleep disturbances in children and adolescents with chronic kidney
      disease.
AB  - Although sleep disorders are common in adults with chronic kidney disease, little
      is known about the prevalence of sleep problems in children and adolescents with
      chronic kidney disease and their relationship to health-related quality of life
      measurements. We performed a clinic-based survey of sleep habits and common
      symptoms of sleep disturbances in 159 school-aged patients with chronic kidney
      disease. Three patient groups of chronic kidney disease were assessed: group 1,
      those not on dialysis and not transplanted; group 2, those on dialysis; and group
      3, those with a functioning renal allograft. Four symptom domains for sleep
      disorders were assessed: excessive daytime sleepiness; sleep disordered
      breathing; restless legs syndrome symptoms; and insufficient sleep. Patients and
      the parent-proxy also completed the Pediatric Quality of Life Inventory Version
      4.0 Generic Core Scales questionnaire. Ninety-three (93) patients (58.5%) had
      symptoms of a sleep disturbance. The presence of a sleep disturbance correlated
      with a decrease in health-related quality of life scores that was independent of
      the chronic kidney disease study group or estimated glomerular filtration rate.
      We conclude that sleep disturbances are common throughout the spectrum of chronic
      kidney disease in children and adolescents and are associated with diminished
      health-related quality of life scores.

PMID- 21964557
TI  - Recovery from auditory and visual neglect after optokinetic stimulation with
      pursuit eye movements--transient modulation and enduring treatment effects.
AB  - Optokinetic stimulation (OKS) modulates many facets of the neglect syndrome. This
      sensory stimulation technique is known to activate multiple brain regions
      (temporo-parietal cortex, basal ganglia, brain stem, cerebellum) some of which
      are involved in auditory and visual space coding. Here, we evaluated whether OKS
      modulates auditory neglect transiently and induces a sustained effect (Study 1),
      and whether repetitive OKS permanently recovers auditory neglect (Study 2). In
      Study 1, 20 patients with visuospatial neglect and auditory neglect in an
      auditory midline task following rightsided stroke were randomly allocated to an
      experimental and a control group matched for neglect severity and socio
      demographic factors. Both groups showed a stable, pathological shift of their
      auditory subjective median plane (ASMP) in front space to the right side. During
      leftward OKS the experimental group showed a complete normalization of the shift
      of the ASMP, which endured until 30 min poststimulation, and returned almost to
      baseline values 24h after OKS. In contrast, the control group who viewed the
      identical but static dot pattern, showed neither change in their ASMP during this
      condition, nor any significant change at 30 min or 24h poststimulation. In Study
      2, we show in two samples of neglect patients (N = 3 each) that repetitive
      leftward OKS with smooth pursuit eye movements as a therapy induces lasting
      improvements in auditory (the ASMP) and visual neglect while visual scanning
      therapy yielded no measurable effects on auditory and significantly smaller
      effects on visual neglect. In conclusion, the experiments show that a single
      session of OKS induces rapid though transient recovery from auditory neglect
      including a sustained effect after termination of stimulation, while repetitive
      OKS therapy yields enduring and multimodal recovery from auditory and visual
      neglect. OKS therapy with pursuit eye movements therefore represents a
      multimodally effective and easily applicable technique for the treatment of
      auditory and visual neglect.

PMID- 21964558
TI  - Differential effects of heart rate reduction with ivabradine in two models of
      endothelial dysfunction and oxidative stress.
AB  - Heart rate reduction with the I(f)-channel-inhibitor ivabradine is a novel and
      appealing option in the therapy of patients with ischemic heart disease. The aim
      of the current study was to determine the effects of ivabradine in two different
      animal models of vascular disease characterized by increased oxidative stress and
      endothelial dysfunction. Wistar rats with angiotensin II induced hypertension and
      ApoE knockout mice were used as animal models of endothelial dysfunction and
      oxidative stress, with half of the animals receiving ivabradine 10 mg/kg/day in
      parallel. Ivabradine lead to a sustained 15-20% heart rate reduction, but had no
      effect on blood pressure. While ivabradine had no effect on endothelial function
      and vascular reactive oxygen species production in angiotensin II-treated rats,
      it improved both parameters in ApoE knockout mice. These antioxidative effects
      were associated with a decreased NADPH oxidase activity and the prevention of
      eNOS uncoupling. In addition, ivabradine treatment led to an attenuation of
      angiotensin II signaling and increased the expression of telomere-stabilizing
      proteins in ApoE knockout mice, which may explain its beneficial effects on the
      vasculature. The absence of these protective ivabradine effects in angiotensin II
      infused rats may relate to the treatment duration or the presence of arterial
      hypertension.

PMID- 21964559
TI  - Microbubble transport through a bifurcating vessel network with pulsatile flow.
AB  - Motivated by two-phase microfluidics and by the clinical applications of air
      embolism and a developmental gas embolotherapy technique, experimental and
      theoretical models of microbubble transport in pulsatile flow are presented. The
      one-dimensional time-dependent theoretical model is developed from an unsteady
      Bernoulli equation that has been modified to include viscous and unsteady
      effects. Results of both experiments and theory show that roll angle (the angle
      the plane of the bifurcating network makes with the horizontal) is an important
      contributor to bubble splitting ratio at each bifurcation within the bifurcating
      network. When compared to corresponding constant flow, pulsatile flow was shown
      to produce insignificant changes to the overall splitting ratio of the bubble
      despite the order one Womersley numbers, suggesting that bubble splitting through
      the vasculature could be modeled adequately with a more modest constant flow
      model. However, bubble lodging was affected by the flow pulsatility, and the
      effects of pulsatile flow were evident in the dependence of splitting ratio of
      bubble length. The ability of bubbles to remain lodged after reaching a steady
      state in the bifurcations is promising for the effectiveness of gas embolotherapy
      to occlude blood flow to tumors, and indicates the importance of understanding
      where lodging will occur in air embolism. The ability to accurately predict the
      bubble dynamics in unsteady flow within a bifurcating network is demonstrated and
      suggests the potential for bubbles in microfluidics devices to encode information
      in both steady and unsteady aspects of their dynamics.

PMID- 21964560
TI  - Cationic antimicrobial peptides in clinical development, with special focus on
      thanatin and heliomicin.
AB  - Cationic host-defence antimicrobial peptides are recognised as an important
      component of the innate immune response in most multicellular organisms. In
      humans, several antimicrobial peptides have recently been recognised as key
      factors in the pathology of diseases such as cystic fibrosis, septic shock,
      atopic dermatitis and morbus Kostmann. To date, several hundred cationic
      antimicrobial peptides have been characterised. They are amphipathic peptides,
      comprising 20 to 50 amino acids, and exhibiting large structural diversity. These
      peptides display a broad spectrum of activity against bacterial, fungal and viral
      pathogens. Their mode of action is best known for cecropins and magainins, which
      act upon the cytoplasmic membrane of microorganisms, causing its disruption by a
      detergent-like activity and pore formation. In the last few years, several of
      these peptides or analogues (derived from magainin, protegrin, indolicidin and
      histatin) were in advanced clinical development, especially for localised
      infections (oral and cutaneous infections, pneumonias etc.). Several other
      molecules (rBPI, heliomicin and thanatin) are currently under development for
      various systemic infections (Staphylococcus sp., Aspergillus sp., Candida sp.
      etc.) and may represent important additions to the anti-infectious therapeutic
      arsenal.

PMID- 21964561
TI  - The role of SDF-1alpha/Rac pathway in the regulation of endothelial progenitor
      cell polarity; homing and expression of Rac1, Rac2 during endothelial repair.
AB  - The Stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) system
      is considered to be of great importance in diseases involving cardiogenesis and
      angiogenesis. The SDF-1alpha-RAC signaling pathway plays a pivotal role in a
      cell's polarity and serves to activate cell morphology variation and to control
      the direction of migration. We aimed to study whether the polarity of endothelial
      progenitor cells (EPCs) is changed by the induction of the SDF-1alpha-RAC
      signaling pathway, to investigate the mechanism of the effect of polarity on the
      homing action of EPCs, and to explore the gene and protein expression of Rac1/2
      during endothelial repair. We measured the EPC characteristics of polarity
      induced by various final concentrations of SDF-1alpha; our observations included
      morphology variation, migration direction, and excursion. Of the dynamic
      variation and cytoskeleton rearrangement of EPCs induced by different final
      concentrations of SDF-1alpha, the most obvious variation was exhibited at the SDF
      1alpha concentration of 200 ng/ml. Obvious polarity variations were also found in
      the EPCs and signal receptors induced by the SDF-1alpha concentration of 200
      ng/ml. The Western blot analysis of Rac1 and Rac2 showed that the addition of AMD
      3100 significantly inhibited the expression of Rac. The SDF-1alpha pathway
      potentially regulates the expression of Rac1/2. The actual excursion vector and
      the direction of the migration of EPCs induced by SDF-1alpha follows polarity,
      thus indicating the importance of further exploration regarding the homing
      induction of EPCs.

PMID- 21964562
TI  - The potential role of RTN3 in monocyte recruitment and atherosclerosis.
AB  - The recruitment of monocytes to arterial wall and their transformation into
      macrophages are generally accepted as important early events in the pathogenesis
      of atherosclerosis (AS). Our research group found Reticulon3 (RTN3), a member of
      the reticulon family, may be a candidate pathogenic element in the progress of
      AS. But it is virtually unknown in which process RTN3 may participate in and
      regulate the pathogenesis of AS. Here, we hypothesis that RTN3 may participate in
      the continuous process of circulating monocyte recruitment in AS including: (1)
      monocyte spreading and adhesion to luminal endothelium; (2) transendothelial
      migration and may also contribute to the conversion of monocyte to macrophage in
      subendothelium.

PMID- 21964563
TI  - Gestational diabetes affects postnatal development of transport and enzyme
      functions in rat intestine.
AB  - The effect of alloxan-induced gestational diabetes on the postnatal development
      of brush border disaccharidases and D-glucose transport in rat intestine was
      studied. Pups born to diabetic mothers showed 92-22% increase in blood sugar
      levels compared with the controls. Western blot and RT-PCR analyses revealed that
      the activities of brush border sucrase, lactase and Sodium Glucose Co-transporter
      1 (SGLT1) correlates with protein and mRNA levels in intestine of pups born to
      diabetic rat mothers after 5-45 days of birth. Intestinal histology in pups born
      to diabetic mothers at day 10 and 45 after birth showed distorted cellular
      organization of mucosa with a decrease in the number of secretary goblet cells
      and regression of tubular mass. These findings suggest that the genetic switch in
      utero regulates the postnatal expression of enzyme and transport functions in
      intestine of pups born to diabetic rat mothers. This may influence the growth and
      development of offsprings later in life.

PMID- 21964564
TI  - Multiple anatomical systems embedded within the primate medial temporal lobe:
      implications for hippocampal function.
AB  - A review of medial temporal lobe connections reveals three distinct groupings of
      hippocampal efferents. These efferent systems and their putative memory functions
      are: (1) The 'extended-hippocampal system' for episodic memory, which involves
      the anterior thalamic nuclei, mammillary bodies and retrosplenial cortex,
      originates in the subicular cortices, and has a largely laminar organisation; (2)
      The 'rostral hippocampal system' for affective and social learning, which
      involves prefrontal cortex, amygdala and nucleus accumbens, has a columnar
      organisation, and originates from rostral CA1 and subiculum; (3) The 'reciprocal
      hippocampal-parahippocampal system' for sensory processing and integration, which
      originates from the length of CA1 and the subiculum, and is characterised by
      columnar, connections with reciprocal topographies. A fourth system, the
      'parahippocampal-prefrontal system' that supports familiarity signalling and
      retrieval processing, has more widespread prefrontal connections than those of
      the hippocampus, along with different thalamic inputs. Despite many interactions
      between these four systems, they may retain different roles in memory which when
      combined explain the importance of the medial temporal lobe for the formation of
      declarative memories.

PMID- 21964565
TI  - Characterization of PDZ domain-peptide interactions using an integrated protocol
      of QM/MM, PB/SA, and CFEA analyses.
AB  - Protein-protein interactions, particularly weak and transient ones, are often
      mediated by peptide recognition domains. Characterizing the interaction interface
      of domain-peptide complexes and analyzing binding specificity for modular domains
      are critical for deciphering protein-protein interaction networks. In this
      article, we report the successful use of an integrated computational protocol to
      dissect the energetic profile and structural basis of peptide binding to third
      PDZ domain (PDZ3) from the PSD-95 protein. This protocol employs rigorous quantum
      mechanics/molecular mechanics (QM/MM), semi-empirical Poisson-Boltzmann/surface
      area (PB/SA), and empirical conformational free energy analysis (CFEA) to
      quantitatively describe and decompose systematic energy changes arising from,
      respectively, noncovalent interaction, desolvation effect, and conformational
      entropy loss associated with the formation of 30 affinity-known PDZ3-peptide
      complexes. We show that the QM/MM-, PB/SA-, and CFEA-derived energy components
      can work together fairly well in reproducing experimentally measured affinity
      after a linearly weighting treatment, albeit they are not compatible with each
      other directly. We also demonstrate that: (1) noncovalent interaction and
      desolvation effect donate, respectively, stability and specificity to complex
      architecture, while entropy loss contributes modestly to binding; (2) P(0) and P(
      2) of peptide ligand are the most important positions for determining both the
      stability and specificity of the PDZ3-peptide complex, P(-1) and P(-3) can confer
      substantial stability (but not specificity) for the complex, and N-terminal P(-4)
      and P(-5) have only a very limited effect on binding.

PMID- 21964566
TI  - Antihypertensive effect of Melothria maderaspatana leaf fractions on DOCA-salt
      induced hypertensive rats and identification of compounds by GC-MS analysis.
AB  - The present study was designed to investigate the antihypertensive effect of
      Melothria maderaspatana leaf fractions on deoxycorticosterone acetate (DOCA)-salt
      induced hypertensive rats and to identify compounds from the active fraction by
      GC-MS analysis. Administration of DOCA salt significantly increased the systolic
      and diastolic blood pressure compared to sham-operated control rats. When treated
      with chloroform (CFM), ethyl acetate (EAFM) or methanol fractions of M.
      maderaspatana (MFM), EAFM alone significantly lowered the systolic and diastolic
      blood pressure. The levels of magnesium and copper significantly increased in
      plasma and decreased in tissues while the zinc level significantly increased in
      plasma and tissues, and administration of EAFM brought these parameters back to
      sham-operated control levels. By GC-MS analysis, phytochemicals such as coumarin,
      vallinic acid, p-coumaric acid, gallic acid, caffeic acid, and ferulic acid were
      identified in EAFM. In conclusion, the EAFM controls blood pressure in DOCA-salt
      hypertensive rats and reverts the metabolic alterations in magnesium, copper and
      zinc.

PMID- 21964567
TI  - Evaluation of porcine mesenchymal stem cells for therapeutic use in human liver
      cancer.
AB  - Mesenchymal stem cell (MSC) transplantation is suggested for therapy of end-stage
      liver disease, due to e.g. liver cancer and metastasis. Liver transplantation is
      the only therapeutic option so far but donor organs are short. Also, the
      availability of allogeneic human MSCs for liver regeneration is limited.
      Therefore, we evaluated the suitability of porcine bone marrow MSCs from semi
      adult pigs and found that morphology, surface expression pattern and multilineage
      differentiation are similar to those of human MSCs. Porcine MSCs differentiated
      to a hepatocyte-like phenotype and expressed porcine mRNA of typical liver
      proteins. However, hepatocyte-like MSCs failed to express the corresponding
      proteins and did not produce glycogen and urea as primary porcine hepatocytes do.
      Porcine MSCs were immunotolerated, since they did not activate resting human
      PBMCs, and were not attacked by human activated PBMCs. However, porcine MSCs led
      to enhanced proliferation of human pre-activated PBMCs suggesting that
      immunotoleration of porcine MSCs in the human system has limitations. Together,
      the potential of porcine MSCs for xenogenous use in human liver therapy is
      promising but needs further evaluation prior to clinical use.

PMID- 21964569
TI  - Advancing the evidence base in rehabilitation for military personnel and
      veterans.

PMID- 21964568
TI  - Comparative analysis of human-derived feeder layers with 3T3 fibroblasts for the
      ex vivo expansion of human limbal and oral epithelium.
AB  - Corneal transplantation with cultivated limbal or oral epithelium is a feasible
      treatment option for limbal stem cell deficiency (LSCD). Currently utilized co
      culture of stem cells with murine 3T3 feeder layer renders the epithelial
      constructs as xenografts. To overcome the potential risks involved with
      xenotransplantation, we investigated the use of human-derived feeder layers for
      the ex vivo expansion of epithelial (stem) cells. Human limbal and oral
      epithelium was co-cultured with mouse 3T3 fibroblasts, human dermal fibroblasts
      (DF), human mesenchymal stem cells (MSC), and with no feeder cells (NF). Cell
      morphology was monitored with phase-contrast microscopy, and stem cell
      characteristics were assessed by immunohistochemistry, real-time PCR for p63 and
      ABCG2, (stem cell markers), and by colony-forming efficiency (CFE) assay.
      Immunohistochemical analysis detected positive staining for CK3 (cornea specific
      marker) and Ibeta1 and p63 (putative stem cell markers) in all culture
      conditions. The level of Ibeta1 and p63 was significantly higher in both limbal
      and oral cells cultured on the 3T3 feeder, as compared to the MSC or NF group
      (p<0.01). This level was comparable to the cells cultured on DF. Expression of
      p63 and ABCG2 in limbal and oral epithelial cells in the 3T3 and DF groups was
      significantly higher than that in the MSC or NF group (p<0.01). No statistical
      difference was detected between 3T3 and DF groups. The CFE of both limbal and
      oral cells co-cultured on 3T3 fibroblasts was comparable to cells grown on DF,
      and was significantly higher than that of cells co-cultured with MSC or NF
      (p<0.01). Epithelial cells grown on a DF feeder layer maintained a stem cell-like
      phenotype, comparable to cells grown on a 3T3 feeder layer. In conclusion, DF
      provides a promising substitute for 3T3 feeder cells during cultivation of
      xenobiotic-free corneal equivalents.

PMID- 21964570
TI  - Comparative metabolite analysis to understand lactate metabolism shift in Chinese
      hamster ovary cell culture process.
AB  - A metabolic shift from lactate production (LP) to net lactate consumption (LC)
      phenotype was observed in certain Chinese hamster ovary (CHO) cell lines during
      the implementation of a new chemically defined medium (CDM) formulation for
      antibody production. In addition, this metabolic shift typically leads to process
      performance improvements in cell growth, productivity, process robustness, and
      scalability. In our previous studies, a correlation between a key media
      component, copper, and this lactate metabolism shift was observed. To further
      investigate this phenomenon, two complementary studies were conducted. In the
      first study, a single cell line was cultivated in two media that only differed in
      their copper concentrations, yet were known to generate an LP or LC phenotype
      with that cell line. In the second study, two different cell lines, which were
      known to possess inherently different lactate metabolic characteristics, were
      cultivated in the same medium with a high level of copper; one cell line produced
      lactate throughout the duration of the culture, and the other consumed lactate
      after an initial period of LP. Cell pellet and supernatant samples from both
      studies were collected at regular time intervals, and their metabolite profiles
      were investigated. The primary finding from the metabolic analysis was that the
      cells in LP conditions exhibited a less efficient energy metabolism, with glucose
      primarily being converted into pyruvate, sorbitol, lactate, and other glycolytic
      intermediates. This decrease in energy efficiency may be due to an inability of
      pyruvate and acetyl-CoA to progress into the TCA cycle. The lack of progression
      into the TCA cycle or overflow metabolism in the LP phenotype resulted in the
      inadequate supply of ATP for the cells. As a consequence, the glycolysis pathway
      remained the major source of ATP, which in turn, resulted in continuous LP
      throughout the culture. In addition, the accumulation of free fatty acids was
      observed; this was thought to be a result of phospholipid catabolism that was
      being used to supplement the energy produced through glycolysis in order to meet
      the needs of LP cells. A thorough review of the metabolic profiles indicated that
      the lactate metabolic shift could be related to the oxidative metabolic capacity
      of cells.

PMID- 21964571
TI  - Chiral phosphinoferrocene carboxamides with amino acid substituents as ligands
      for Pd-catalysed asymmetric allylic substitutions. Synthesis and structural
      characterisation of catalytically relevant Pd complexes.
AB  - An extensive series of chiral amino acid amides prepared from 1'
      (diphenylphosphino)ferrocene-1-carboxylic acid (Hdpf) or its planar-chiral
      isomer, 2-(diphenylphosphino)ferrocene-1-carboxylic acid, have been tested as
      ligands for Pd-catalysed asymmetric allylic substitution reactions. In alkylation
      of 1,3-diphenylallyl acetate as a model substrate with dimethyl malonate the
      ligands performed well in terms of both reaction rate and enantioselectivity,
      achieving up to 98% ee. In contrast, the reactions of the same substrate with
      other nucleophiles proceeded either slowly and with poor ee's (amination with
      benzylamine) or not at all (etherification with benzyl alcohol). In order to
      rationalise the influence of the ligand structure on the reaction course, three
      model complexes, viz. [(eta(3)-methallyl)PdCl(L-kappaP)], [(eta(3)-methallyl)Pd(L
      kappa(2)O,P)]ClO(4) and [(eta(3)-methallyl)Pd(L-kappaP)(2)]ClO(4) have been
      prepared from the achiral amide Ph(2)PfcCONHCH(2)CO(2)Me (L; fc = ferrocene-1,1'
      diyl) and structurally characterised. The coordination study showed that the
      amido-phosphines readily form 1 : 1 complexes as O,P-chelates where the amino
      acid chirality is brought close to the Pd atom. At higher ligand-to-metal ratios,
      however, simple P-monodentate coordination prevails, minimising the influence of
      the chiral amino acid pendant.

PMID- 21964572
TI  - Inverted genomic segments and complex triplication rearrangements are mediated by
      inverted repeats in the human genome.
AB  - We identified complex genomic rearrangements consisting of intermixed
      duplications and triplications of genomic segments at the MECP2 and PLP1 loci.
      These complex rearrangements were characterized by a triplicated segment embedded
      within a duplication in 11 unrelated subjects. Notably, only two breakpoint
      junctions were generated during each rearrangement formation. All the complex
      rearrangement products share a common genomic organization, duplication-inverted
      triplication-duplication (DUP-TRP/INV-DUP), in which the triplicated segment is
      inverted and located between directly oriented duplicated genomic segments. We
      provide evidence that the DUP-TRP/INV-DUP structures are mediated by inverted
      repeats that can be separated by >300 kb, a genomic architecture that apparently
      leads to susceptibility to such complex rearrangements. A similar inverted repeat
      mediated mechanism may underlie structural variation in many other regions of the
      human genome. We propose a mechanism that involves both homology-driven events,
      via inverted repeats, and microhomologous or nonhomologous events.

PMID- 21964573
TI  - Identification of genetic elements that autonomously determine DNA methylation
      states.
AB  - Cytosine methylation is a repressive, epigenetically propagated DNA modification.
      Although patterns of DNA methylation seem tightly regulated in mammals, it is
      unclear how these are specified and to what extent this process entails genetic
      or epigenetic regulation. To dissect the role of the underlying DNA sequence, we
      sequentially inserted over 50 different DNA elements into the same genomic locus
      in mouse stem cells. Promoter sequences of approximately 1,000 bp autonomously
      recapitulated correct DNA methylation in pluripotent cells. Moreover, they
      supported proper de novo methylation during differentiation. Truncation analysis
      revealed that this regulatory potential is contained within small methylation
      determining regions (MDRs). MDRs can mediate both hypomethylation and de novo
      methylation in cis, and their activity depends on developmental state, motifs for
      DNA-binding factors and a critical CpG density. These results demonstrate that
      proximal sequence elements are both necessary and sufficient for regulating DNA
      methylation and reveal basic constraints of this regulation.

PMID- 21964574
TI  - Mutations in TRPV4 cause an inherited arthropathy of hands and feet.
AB  - Familial digital arthropathy-brachydactyly (FDAB) is a dominantly inherited
      condition that is characterized by aggressive osteoarthropathy of the fingers and
      toes and consequent shortening of the middle and distal phalanges. Here we show
      in three unrelated families that FDAB is caused by mutations encoding
      p.Gly270Val, p.Arg271Pro and p.Phe273Leu substitutions in the intracellular
      ankyrin-repeat domain of the cation channel TRPV4. Functional testing of mutant
      TRPV4 in HEK-293 cells showed that the mutant proteins have poor cell-surface
      localization. Calcium influx in response to the synthetic TRPV4 agonists
      GSK1016790A and 4alphaPDD was significantly reduced, and mutant channels did not
      respond to hypotonic stress. Others have shown that gain-of-function TRPV4
      mutations cause skeletal dysplasias and peripheral neuropathies. Our data
      indicate that TRPV4 mutations that reduce channel activity cause a third
      phenotype, inherited osteoarthropathy, and show the importance of TRPV4 activity
      in articular cartilage homeostasis. Our data raise the possibility that TRPV4 may
      also have a role in age- or injury-related osteoarthritis.

PMID- 21964576
TI  - Halogen bonding in ligand-receptor systems in the framework of classical force
      fields.
AB  - Halogen bond is an important non-covalent interaction which is receiving a
      growing attention in the study of protein-ligand complexes. Many drugs are
      halogenated molecules and it has been recently shown that many halogenated
      ligands establish halogen bonds with biomolecules. As the halogen bond nature is
      due to an anisotropy of the electrostatic potential around halogen atoms, it is
      not possible to use traditional force fields based on a set of atom-centred
      charges to study halogen bonds in biomolecules. We show that the introduction of
      pseudo-atoms on halogens permits us to correctly describe the anisotropy of the
      electrostatic potential and to perform molecular dynamics simulations on
      complexes of proteins with halogenated ligands that reproduce experimental
      values. The results are compared with crystallographic data and with hybrid
      quantum mechanics/molecular mechanics calculations.

PMID- 21964577
TI  - Pregnenolone derivatives as potential anticancer agents.
AB  - Pregnenolone (1) was used as a template to develop new anticancer compounds. Ring
      D modification of 1 resulted in the synthesis of benzylidenes 2-17, pyrazolines
      18-76, pyrazoles 85-91, hydrazones 77-84, and oximes 92-107 derivatives. The
      structure of compound 107 was also deduced through single crystal X-ray
      diffraction studies. The inclusion of furanyl and pyridyl rings to pregnenolone
      skeleton increases the cytotoxicity of all compounds significantly. Among
      benzylidene derivatives, only heterocyclic enone 8 (IC50=0.74 MUM/mL against
      HepG2), and 17 (IC50=4.49 MUM/mL against HepG2, IC50=5.01 MUM/mL against MDA-MB
      230 cancer cell line) exhibited a significant activity. The cytotoxicity data of
      pyrazoline derivatives 18-76 revealed that only furanyl bearing pyrazolines 40,
      42-44, 48, and 49 exhibited significant activities. While all (O-carboxymethyl)
      oximes, hydazones, and pyrazoles derivatives of pregnenolone did not show any
      significant activity against both the cell lines. Thus the furanyl bearing enone
      8 (IC50=0.74 MUM/mL against HepG2), and its pyrazoline derivative 48 (IC50=0.91
      MUM/mL against MDA-MB-230 cancer cell lines) were identified as the most active
      compounds in all derivatives of pregnenolone.

PMID- 21964575
TI  - Mutations in BRIP1 confer high risk of ovarian cancer.
AB  - Ovarian cancer causes more deaths than any other gynecologic malignancy in
      developed countries. Sixteen million sequence variants, identified through whole
      genome sequencing of 457 Icelanders, were imputed to 41,675 Icelanders genotyped
      using SNP chips, as well as to their relatives. Sequence variants were tested for
      association with ovarian cancer (N of affected individuals = 656). We discovered
      a rare (0.41% allelic frequency) frameshift mutation, c.2040_2041insTT, in the
      BRIP1 (FANCJ) gene that confers an increase in ovarian cancer risk (odds ratio
      (OR) = 8.13, P = 2.8 * 10(-14)). The mutation was also associated with increased
      risk of cancer in general and reduced lifespan by 3.6 years. In a Spanish
      population, another frameshift mutation in BRIP1, c.1702_1703del, was seen in 2
      out of 144 subjects with ovarian cancer and 1 out of 1,780 control subjects (P =
      0.016). This allele was also associated with breast cancer (seen in 6/927 cases;
      P = 0.0079). Ovarian tumors from heterozygous carriers of the Icelandic mutation
      show loss of the wild-type allele, indicating that BRIP1 behaves like a classical
      tumor suppressor gene in ovarian cancer.

PMID- 21964578
TI  - Hook plate fixation for acromioclavicular joint separations restores
      coracoclavicular distance more accurately than PDS augmentation, however presents
      with a high rate of acromial osteolysis.
AB  - INTRODUCTION: Hook plate fixation of acromioclavicular (AC) joint separations
      carries the disadvantage of compulsory implant removal, occasional implant
      fatigue and secondary loss of reduction. This study compares the clinical and
      radiological outcome of a new polyaxial angular stable hook plate (HP) with
      absorbable polydioxansulfate (PDS) sling. MATERIALS AND METHODS: Between 2002 and
      2009, out of a consecutive series of 81 patients with symptomatic Rockwood type V
      lesions 52 patients received clinical and radiographic follow-up (HP: n = 27;
      PDS: n = 25). HP patients were prospectively analyzed and retrospectively
      compared with the PDS group. Radiological follow-up included comparative coraco-
      and acromioclavicular distance (CCD/ACD) measurements as percentage of the
      uninjured shoulder. For clinical follow-up a standardized functional shoulder
      assessment with Constant Score, DASH Score, Taft Score and a self-report
      questionnaire including the visual analog scale (VAS) was carried out. RESULTS:
      Direct postoperative radiographs showed an overcorrection of CCD in the HP group
      (-4.4% of the uninjured side) and failure of anatomic correction in the PDS group
      (+11.0%). After implant removal, CCD increased in the HP group extensively to
      16.7% (overall loss of reduction: 21.1%) and 23.9% in the PDS group.
      Redisplacement (100% increase of CCD) occurred in five cases (HP: 2, PDS: 3) and
      partial loss of reduction in four cases of each group. Comparing functional
      results no differences could be seen between both the groups (Constant-Score HP:
      91.2 points, PDS: 94.6 points; Taft-Score HP: 9.4 points, PDS: 10.0 points). The
      DASH-Score revealed better results for PDS group (3.4 points, HP: 8.0 points).
      Signs of acromial osteolysis appeared in five cases (18.5%) in HP group. There
      was no case of implant failure. The X-rays of six patients (HP: 4, PDS: 2) showed
      AC-joint-osteoarthritis. CONCLUSION: Hook plate fixation employing a polyaxial
      angular stable plate finally restores the coracoclavicular distance more
      accurately than augmentation with a PDS sling. Although in HP group no implant
      failure occurred, major disadvantages are initial overcorrection and acromial
      osteolysis. Both have no influence on final functional results.

PMID- 21964579
TI  - Improving communication of breast cancer recurrence risk.
AB  - Doctors commonly use genomic testing for breast cancer recurrence risk. We sought
      to assess whether the standard genomic report provided to doctors is a good
      approach for communicating results to patients. During 2009-2010, we interviewed
      133 patients with stages I or II, node-negative, hormone receptor-positive breast
      cancer and eligible for the Oncotype DX genomic test. In a randomized experiment,
      patients viewed six vignettes that presented hypothetical recurrence risk test
      results. Each vignette described a low, intermediate, or high chance of breast
      cancer recurrence in 10 years. Vignettes used one of five risk formats of
      increasing complexity that we derived from the standard report that accompanies
      the commercial assay or a sixth format that used an icon array. Among women who
      received the genomic recurrence risk test, 63% said their doctors showed them the
      standard report. The standard report format yielded among the most errors in
      identification of whether a result was low, intermediate, or high risk (i.e., the
      gist of the results), whereas a newly developed risk continuum format yielded the
      fewest errors (17% vs. 5%; OR 0.23; 95% CI 0.10-0.52). For high recurrence risk
      results presented in the standard format, women made errors 35% of the time.
      Women rated the standard report as one of the least understandable and least
      liked formats, but they rated the risk continuum format as among the most
      understandable and most liked. Results differed little by health literacy,
      numeracy, prior receipt of genomic test results during clinical care, and actual
      genomic test results. The standard genomic recurrence risk report was more
      difficult for women to understand and interpret than the other formats. A less
      complex report, potentially including the risk continuum format, would be more
      effective in communicating test results to patients.

PMID- 21964580
TI  - Renalase gene polymorphisms in patients with type 2 diabetes, hypertension and
      stroke.
AB  - Renalase is a novel, recently identified, flavin adenine dinucleotide-dependent
      amine oxidase. It is secreted by the kidney and metabolizes circulating
      catecholamines. Renalase has significant hemodynamic effects, therefore it is
      likely to participate in the regulation of cardiovascular function.The aim of our
      study was to investigate the involvement of renalase gene polymorphisms in
      hypertension in type 2 diabetes patients. A total of 892 patients and 400
      controls were genotyped with three SNPs in the renalase gene. The C allele of
      rs2296545 SNP was associated with hypertension (P < 0.01). For rs2576178 SNP,
      frequencies in hypertensive patients differed from controls, but not from
      normotensive patients. For rs10887800 SNP, the differences in the G allele
      frequencies were observed in hypertensive patients with stroke, with 66% of
      patients being GG homozygotes. To confirm observed association we later genotyped
      130 stroke patients without diabetes. The OR for risk allele was 1.79 (95% CI
      1.33-2.41). In conclusion, the renalase gene polymorphism was associated with
      hypertension in type 2 diabetes patients. The most interesting result is a strong
      association of the rs10887800 polymorphism with stroke in patients with and
      without diabetes. The G allele of this polymorphism might thus be useful in
      identifying diabetes patients at increased risk of stroke.

PMID- 21964581
TI  - Biliary tract tuberculosis--a diagnostic dilemma.
AB  - INTRODUCTION: Most western patients who have not had a previous operation and
      present with biliary obstruction are thought to have a malignant lesion. However
      in our country where the disease is common, we found that some of these patients
      had a tuberculous cause which considerably altered their management as well as
      their prognosis. We herein present our experience of these patients whom we had
      operated with a preoperative diagnosis of biliary tract malignancy and discuss,
      retrospectively, how they might have been detected before operation to have
      tuberculosis. METHODS: Between August 1996 and June 2010, we operated on 209
      patients with a preoperative diagnosis of carcinoma of the gallbladder and common
      bile duct. Seven out of these 209 patients had biliary tuberculosis. We
      retrospectively analyzed the clinical features of these patients from our
      prospectively maintained database. RESULTS: There were four males and three
      females who had a mean age of 54 (32-65) years. The bile duct was involved in
      four and gallbladder in three patients. In contrast to those with malignancy,
      patients with tuberculosis had a longer history (122 vs 44 days), an abdominal
      mass was present less frequently (28% vs 57%), the serum bilirubin was lower (1.6
      vs 6 mg/dl), and they also had evidence of tuberculosis elsewhere in the body
      (28.5%). There was no operative mortality in biliary tract tuberculosis in
      contrast to 7.5% in biliary tract malignancy. CONCLUSION: Though tuberculosis of
      the biliary tract is rare, it needs to be considered in the differential
      diagnosis of patients with biliary obstruction especially in countries where the
      disease is endemic.

PMID- 21964582
TI  - The role of integrated F-18-FDG-PET scanning in the detection of M1 disease in
      oesophageal adenocarcinoma and impact on clinical management.
AB  - INTRODUCTION: The aim of this study was to evaluate the efficacy of F-18
      fluorodeoxyglucose positron emission tomography (FDG-PET) scanning in the staging
      of oesophageal adenocarcinoma. METHODS: One hundred four patients with biopsy
      proven adenocarcinoma underwent (18)F-FDG-PET scan. FDG avid lesions were further
      investigated to their diagnostic conclusion. RESULTS: Nineteen patients (18.26%)
      were found to have non-loco-regional FDG uptake. Of the patients, 3.84% were
      found to have M1 disease and 7.69% were found to have a second primary tumour.
      The sensitivity and specificity of FDG-PET scanning to detect metastatic disease
      in our series was 57.14% and 84.53%, respectively. The overall diagnostic
      accuracy was 82.69%. CONCLUSIONS: PET scanning improves staging and prevents
      unnecessary surgery in patients with M1 disease. It represents a good adjunct to
      computed tomography scanning and endoscopic ultrasound in the staging of
      oesophageal adenocarcinoma. The detection of asymptomatic coexisting synchronous
      cancers is an added benefit provided by PET scanning over similar diagnostic
      modalities.

PMID- 21964583
TI  - Robotic-assisted proctectomy for inflammatory bowel disease: a case-matched
      comparison of laparoscopic and robotic technique.
AB  - BACKGROUND: The objective of this study was to compare short-term outcomes of
      robotic and laparoscopic proctectomy in patients with inflammatory bowel disease
      (IBD). METHODS: This is an IRB-approved case-matched review. Seventeen robotic
      proctectomies (RP), 10 with ileal pouch anal anastomosis (IPAA) and 7 completion
      (CP), were matched to laparoscopic proctectomies (LP). Short-term and functional
      outcomes were compared between LP and RP. RESULTS: In CP cohort, operative times
      were longer in the RP group (351 RP vs 238 LP min, p = 0.03), mean robotic time
      90 min. Estimated blood loss (EBL) was similar between RP-CP and LP-CP groups (p
      = 0.18). Return of bowel function (RBF) was slower in RP-CP group (3.0 vs 1.7
      days, p = 0.04), and length of stay (LOS) was longer (6.4 vs 4.1 days, p = 0.02).
      In the IPAA group, there were no differences between operative times (p = 0.14),
      robotic time 86 min; EBL (p = 0.15), and postoperative complications. Return of
      bowel function (3.6 vs 2.6 days, p = 0.3) and LOS (8.5 vs 6.1 days, p = 0.17)
      were similar between RP and LP. Bowel and sexual function were equivalent between
      LP and RP-IPAA groups. CONCLUSIONS: Robotic proctectomy is a safe and effective
      technique for patients with IBD. It is comparable to LP with regard to
      perioperative outcomes, complications, and short-term functional results.

PMID- 21964584
TI  - Statistical properties of superimposed stationary spike trains.
AB  - The Poisson process is an often employed model for the activity of neuronal
      populations. It is known, though, that superpositions of realistic, non- Poisson
      spike trains are not in general Poisson processes, not even for large numbers of
      superimposed processes. Here we construct superimposed spike trains from
      intracellular in vivo recordings from rat neocortex neurons and compare their
      statistics to specific point process models. The constructed superimposed spike
      trains reveal strong deviations from the Poisson model. We find that
      superpositions of model spike trains that take the effective refractoriness of
      the neurons into account yield a much better description. A minimal model of this
      kind is the Poisson process with dead-time (PPD). For this process, and for
      superpositions thereof, we obtain analytical expressions for some second-order
      statistical quantities-like the count variability, inter-spike interval (ISI)
      variability and ISI correlations-and demonstrate the match with the in vivo data.
      We conclude that effective refractoriness is the key property that shapes the
      statistical properties of the superposition spike trains. We present new,
      efficient algorithms to generate superpositions of PPDs and of gamma processes
      that can be used to provide more realistic background input in simulations of
      networks of spiking neurons. Using these generators, we show in simulations that
      neurons which receive superimposed spike trains as input are highly sensitive for
      the statistical effects induced by neuronal refractoriness.

PMID- 21964585
TI  - A longitudinal model for magnetic resonance imaging lesion count data in multiple
      sclerosis patients.
AB  - Magnetic resonance imaging (MRI) data are routinely collected at multiple time
      points during phase 2 clinical trials in multiple sclerosis. However, these data
      are typically summarized into a single response for each patient before analysis.
      Models based on these summary statistics do not allow the exploration of the
      trade-off between numbers of patients and numbers of scans per patient or the
      development of optimal schedules for MRI scanning. To address these limitations,
      in this paper, we develop a longitudinal model to describe one MRI outcome: the
      number of lesions observed on an individual MRI scan. We motivate our choice of a
      mixed hidden Markov model based both on novel graphical diagnostic methods
      applied to five real data sets and on conceptual considerations. Using this
      model, we compare the performance of a number of different tests of treatment
      effect. These include standard parametric and nonparametric tests, as well as
      tests based on the new model. We conduct an extensive simulation study using data
      generated from the longitudinal model to investigate the parameters that affect
      test performance and to assess size and power. We determine that the parameters
      of the hidden Markov chain do not substantially affect the performance of the
      tests. Furthermore, we describe conditions under which likelihood ratio tests
      based on the longitudinal model appreciably outperform the standard tests based
      on summary statistics. These results establish that the new model is a valuable
      practical tool for designing and analyzing multiple sclerosis clinical trials.

PMID- 21964586
TI  - Unique CYP3A4 genetic variant in Brazilian tuberculosis patients with/without
      HIV.
AB  - CYP3A4 is involved in tuberculosis (TB) and human immunodeficiency virus (HIV)
      drug metabolism. Transcriptional activation by rifampicin involves the CYP3A4
      gene 5'-upstream region. Consequently, variation may interfere with transcription
      and enzymatic activity and even drug response. However, genetic polymorphisms and
      distribution of CYP3A4 allelic frequencies in individuals from Rio de Janeiro
      remain unknown. The aim of this study was to conduct research into sequencing the
      CYP3A4 5'-upstream region in Brazilian patients with and without HIV. This follow
      up study involved 106 individuals undergoing treatment for TB and/or HIV. The
      CYP3A4 5'-upstream region was analyzed using PCR, sequencing and clinical data.
      Male patients revealed a higher HIV frequency (p=0.021). The TB forms observed
      were pulmonary (48.1%), extrapulmonary (22.64%) and disseminated (27.36%). Lymph
      node form was the most frequent (70.83%) extrapulmonary form of TB. The only
      single nucleotide polymorphism detected in the population was c.-392A>G.
      Genotypes observed were CYP3A4*1A/CYP3A4*1A (45.3%), CYP3A4*1A/CYP3A4*1B (40.6%)
      and CYP3A4*1B/CYP3A4*1B (14.2%), revealing a different distribution with
      extrapulmonary TB cases (17.6% CYP3A4*1A/CYP3A4*1B and 23.5%
      CYP3A4*1B/CYP3A4*1B). The CYP3A4*1A allele was found to be associated with
      tobacco use. The CYP3A4*1B mutant allele occurred in 34% of patients. This study
      revealed that the CYP3A4 5'-upstream regulatory region was highly conserved with
      the exception of the -392 position. Genotype association with tobacco suggests
      that CYP3A4 may participate in tobacco metabolism. Genotype distribution
      inversion in extrapulmonary TB cases suggests that CYP3A4 may be involved in TB
      prognosis.

PMID- 21964587
TI  - Detection of three human adenovirus species in adults with acute respiratory
      infection in China.
AB  - Human adenoviruses (HAdVs) are recognized as causal agents in a wide range of
      human diseases. However, researchers lack sufficient data on the exact HAdV
      species and serotypes associated with adult acute respiratory tract infections
      (ARTIs). To detect and characterize HAdV infections in adults in China, clinical
      specimens were collected from 10,310 adults with ARTIs from May 2005 to July
      2010. The partial HAdV hexon gene was amplified by polymerase chain reaction
      (PCR), sequenced, and phylogenetically analyzed. HAdVs were detected in 86
      samples (0.8%), of which 67 (77.9%) were species B (HAdV-3, -7, -11, and -14), 7
      (8.1%) were species C (HAdV-1, -2, and -6), and 12 (14%) were species E (HAdV-4).
      HAdV-3 was the most frequently detected serotype (41/86, 47.7%), followed by HAdV
      7 (13/86, 15.1%), HAdV-4 (12/86, 14.0%), and HAdV-11 (11/86, 12.8%). Patients 14
      25 years old (60.5%) exhibited a higher rate of adenovirus detection than older
      patients. Co-infections with other respiratory viruses were observed in samples
      positive for HAdV species B and E. Human rhinovirus was the most commonly found
      virus in patients with HAdV infection. These findings provide baseline data for
      the surveillance and control of HAdV infection in China.

PMID- 21964588
TI  - The immune reconstitution inflammatory syndrome related to HIV co-infections: a
      review.
AB  - The immune reconstitution inflammatory syndrome (IRIS) is a consequence of an
      excessive pathogen-specific immune recovery reaction and occurs in a subset of
      patients on antiretroviral therapy (ART). Infective forms of IRIS may present
      either as an 'unmasking' of a previously subclinical infection or the paradoxical
      clinical deterioration of an infection for which the patient received appropriate
      antimicrobial therapy. The most important risk factors for IRIS are a low CD4+ T
      cell count and a short time between treatment of the infection and the
      commencement of ART. The general approach to the treatment of IRIS is to continue
      ART and provide antimicrobial therapy for the provoking infection. The majority
      of cases are self-limiting; however, mortality and hospitalisation rates are
      particularly high when tuberculosis- or cryptococcal-IRIS affects the central
      nervous system (CNS). Corticosteroid therapy should be considered in certain
      forms of IRIS after the exclusion of other conditions that could explain the
      inflammatory manifestations in the patients. Given that a low CD4+ T-cell count
      is a major risk factor for the development of IRIS, commencing ART at a CD4+ T
      cell count of >350/MUL will prevent most cases.

PMID- 21964589
TI  - Seroprevalence for toxoplasmosis in individuals living in north west Tuscany:
      access to Toxo-test in central Italy.
AB  - This survey aimed to estimate the prevalence of anti-Toxoplasma IgG and IgM
      antibodies in people living in north west Tuscany (central Italy) and to
      investigate the adherence to antenatal screening programs and access to the Toxo
      test as well. Sera from a large sample of individuals suspected to have acute
      infection or from pregnant women (10,352 subjects) aged between 1 day and over 70
      years were analysed for both IgG and IgM anti-Toxoplasma antibodies using an
      immunoenzymatic method or a chemo-luminescent immunoassay. Overall, the
      seroprevalence of IgG antibodies was 21.4% (95% CI 20.62-22.20). A positive trend
      according to age was found, with low positivity observed in younger age groups.
      Among women of reproductive age the prevalence of IgG antibodies was 19.4% (95%
      CI 18.64-20.26). The overall IgM seroprevalence was 1.07% (95% CI 0.87-1.27). A
      low IgM prevalence was also observed in women of reproductive age (0.8%; 95% CI
      0.65-1.03). Our study seems to indicate that primary prevention is widespread
      among women. However, an epidemiological surveillance system for toxoplasmosis
      should be implemented, to assess the risk of congenital toxoplasmosis and to
      determine the true burden of disease in adults.

PMID- 21964590
TI  - Value of PCR in surgically treated patients with staphylococcal infective
      endocarditis: a 4-year retrospective study.
AB  - The aim of the study was to establish a diagnostic value for broad-range
      polymerase chain reaction (br-PCR) and staphylococci-specific multiplex PCR (ssm
      PCR) performed on surgical material from patients with staphylococcal infective
      endocarditis (IE). Data were analysed retrospectively from 60 patients with
      suspected staphylococcal IE and 59 controls who were surgically treated at three
      cardiosurgery centres over 4 years. Both PCR tests showed high agreement and
      could be aggregated. In patients with definite and rejected IE, the clinical
      sensitivity and specificity of PCR reached 89 and 95%, respectively. Tissue
      culture (TC) and PCR agreed with blood culture (BC) in 29% and 67% of IE cases.
      TC helped to determine aetiology in five BC negative cases while PCR aided in
      nine cases. Out of 52 patients with conclusive staphylococcal IE, 40 were
      diagnosed with S. aureus and 12 with coagulase-negative staphylococci. PCR was
      shown to be highly superior to TC in confirming preoperative diagnosis of IE. In
      addition to aid in culture negative patients, PCR helped to establish or refine
      aetiology in inconclusive cases. We suggest that simultaneous br-PCR and ssm-PCR
      performed on surgical material together with histopathology could significantly
      increase the performance of current Duke criteria.

PMID- 21964591
TI  - Myostatin induces degradation of sarcomeric proteins through a Smad3 signaling
      mechanism during skeletal muscle wasting.
AB  - Ubiquitination-mediated proteolysis is a hallmark of skeletal muscle wasting
      manifested in response to negative growth factors, including myostatin. Thus, the
      characterization of signaling mechanisms that induce the ubiquitination of
      intracellular and sarcomeric proteins during skeletal muscle wasting is of great
      importance. We have recently characterized myostatin as a potent negative
      regulator of myogenesis and further demonstrated that elevated levels of
      myostatin in circulation results in the up-regulation of the muscle-specific E3
      ligases, Atrogin-1 and muscle ring finger protein 1 (MuRF1). However, the exact
      signaling mechanisms by which myostatin regulates the expression of Atrogin-1 and
      MuRF1, as well as the proteins targeted for degradation in response to excess
      myostatin, remain to be elucidated. In this report, we have demonstrated that
      myostatin signals through Smad3 (mothers against decapentaplegic homolog 3) to
      activate forkhead box O1 and Atrogin-1 expression, which further promotes the
      ubiquitination and subsequent proteasome-mediated degradation of critical
      sarcomeric proteins. Smad3 signaling was dispensable for myostatin-dependent
      overexpression of MuRF1. Although down-regulation of Atrogin-1 expression rescued
      approximately 80% of sarcomeric protein loss induced by myostatin, only about 20%
      rescue was seen when MuRF1 was silenced, implicating that Atrogin-1 is the
      predominant E3 ligase through which myostatin manifests skeletal muscle wasting.
      Furthermore, we have highlighted that Atrogin-1 not only associates with myosin
      heavy and light chain, but it also ubiquitinates these sarcomeric proteins. Based
      on presented data we propose a model whereby myostatin induces skeletal muscle
      wasting through targeting sarcomeric proteins via Smad3-mediated up-regulation of
      Atrogin-1 and forkhead box O1.

PMID- 21964592
TI  - PITX2 AND PITX1 regulate thyrotroph function and response to hypothyroidism.
AB  - Pitx2 is a homeodomain transcription factor required in a dose-dependent manner
      for the development of multiple organs. Pitx2-null homozygotes (Pitx2(-/-)) have
      severe pituitary hypoplasia, whereas mice with reduced-function alleles
      (Pitx2(neo/neo)) exhibit modest hypoplasia and reduction in the developing
      gonadotroph and Pou1f1 lineages. PITX2 is expressed broadly in Rathke's pouch and
      the fetal pituitary gland. It predominates in adult thyrotrophs and gonadotrophs,
      although it is not necessary for gonadotroph function. To test the role of PITX2
      in thyrotroph function, we developed thyrotroph-specific cre transgenic mice,
      Tg(Tshb-cre) with a recombineered Tshb bacterial artificial chromosome that
      ablates floxed genes in differentiated pituitary thyrotrophs. We used the best
      Tg(Tshb-Cre) strain to generate thyrotroph-specific Pitx2-deficient offspring,
      Pitx2(flox/-;)Tg(Tshb-cre). Double immunohistochemistry confirmed Pitx2 deletion.
      Pitx2(flox/-);Tg(Tshb-cre) mice have a modest weight decrease. The thyroid glands
      are smaller, although circulating T(4) and TSH levels are in the normal range.
      The pituitary levels of Pitx1 transcripts are significantly increased, suggesting
      a compensatory mechanism. Hypothyroidism induced by low-iodine diet and oral
      propylthiouracil revealed a blunted TSH response in Pitx2(flox/-);Tg(Tshb-cre)
      mice. Pitx1 transcripts increased significantly in control mice with induced
      hypothyroidism, but they remained unchanged in Pitx2(flox/-);Tg(Tshb-cre) mice,
      possibly because Pitx1 levels were already maximally elevated in untreated
      mutants. These results suggest that PITX2 and PITX1 have overlapping roles in
      thyrotroph function and response to hypothyroidism. The novel cre transgene that
      we report will be useful for studying the function of other genes in thyrotrophs.

PMID- 21964593
TI  - Transgenic overexpression of the transcription factor Nkx6.1 in beta-cells of
      mice does not increase beta-cell proliferation, beta-cell mass, or improve
      glucose clearance.
AB  - The loss or dysfunction of the pancreatic endocrine beta-cell results in
      diabetes. Recent innovative therapeutic approaches for diabetes aim to induce
      beta-cell proliferation in vivo by pharmacological intervention. Based on the
      finding that overexpression of the transcription factor Nkx6.1 in islets in vitro
      increases beta-cell proliferation while maintaining beta-cell function, Nkx6.1
      has been proposed as a potential target for diabetes therapy. However, it is
      unknown whether elevated Nkx6.1 levels in beta-cells in vivo have similar effects
      as observed in isolated islets. To this end, we sought to investigate whether
      overexpression of Nkx6.1 in beta-cells in vivo could increase beta-cell mass
      and/or improve beta-cell function in normal or beta-cell-depleted mice. Using a
      bigenic inducible Cre-recombinase-based transgenic model, we analyzed the effects
      of Nkx6.1 overexpression on beta-cell proliferation, beta-cell mass, and glucose
      metabolism. We found that mice overexpressing Nkx6.1 in beta-cells displayed
      similar beta-cell proliferation rates and beta-cell mass as control mice.
      Furthermore, after partial beta-cell ablation, Nkx6.1 overexpression was not
      sufficient to induce beta-cell regeneration under either nondiabetic or diabetic
      conditions. Together these results demonstrate that sustained Nkx6.1
      overexpression in vivo does not stimulate beta-cell proliferation, expand beta
      cell mass, or improve glucose metabolism in either normal or beta-cell-depleted
      pancreata. Thus, raising cellular Nkx6.1 levels in beta-cells in vivo is unlikely
      to have a positive impact on type 2 diabetes.

PMID- 21964596
TI  - Resolution of enantiomers of a series of chiral alkoxy-modified phthalocyaninato
      nickel(II) complexes by enantioselective HPLC.
AB  - We have resolved the enantiomers of a series of chiral modified
      metallophthalocyaninato complexes of nickel bearing alkoxy groups at the 14 and
      28 positions on what would otherwise be a normal phthalocyaninato ligand and
      conforming to the general formula [14,28-(RO)(2)Pc]Ni(ii), where R = Me, Et, or n
      Pr. The complex for which R = n-Pr is reported here for the first time.
      Resolution of the enantiomers of these complexes was accomplished via HPLC
      utilizing an immobilized carbohydrate-based stationary phase, resulting in
      baseline resolution of peaks corresponding to enantiomers of the complexes, with
      R(s) values in excess of five. Isolation of milligram quantities of the complexes
      bearing methoxy and n-propoxy groups in high enantiomeric excess has been
      achieved via semi-preparative-scale HPLC on the same stationary phase. Resolved
      samples of these compounds do not appear to racemize at an appreciable rate, nor
      do they readily exchange alkoxy groups with alcohols while stirring in alcoholic
      solution. The spectroscopic details and the crystallographically-determined solid
      state structure for the complex where R = n-Pr are reported, and are highly
      similar to those that have been observed for the previously reported analogues.
      It has been shown by NMR that the chirality and C(2) molecular symmetry of the
      complex bearing n-propoxy groups is maintained in solution.

PMID- 21964594
TI  - Minireview: recent developments in the physiology and pathology of the
      lysophosphatidylinositol-sensitive receptor GPR55.
AB  - Emerging data suggest that off-target cannabinoid effects may be mediated via
      novel seven-transmembrane spanning/G protein-coupled receptors. Due to its
      cannabinoid sensitivity, the G protein-coupled receptor 55 (GPR55) was recently
      proposed as a candidate; however, GPR55 is phylogenetically distinct from the
      traditional cannabinoid receptors, and the conflicting pharmacology, signaling,
      and functional data have prevented its classification as a novel cannabinoid
      receptor. Indeed, the most consistent and potent agonist to date is the
      noncannabinoid lysophospholipid, lysophosphatidylinositol. Here we present new
      human GPR55 mRNA expression data, providing supportive evidence of GPR55
      expression in a vast array of tissues and cell types. Moreover, we summarize
      major recent developments in GPR55 research and aim to update the reader in the
      rapidly expanding fields of GPR55 pharmacology, physiology, and pathology.

PMID- 21964595
TI  - Negative cross talk between NFAT1 and Stat5 signaling in breast cancer.
AB  - The molecular mechanisms that modulate the activity of the signal transducers and
      activators of transcription 5 (Stat5) during the progression of breast cancer
      remain elusive. Here, we present evidence that the calcineurin/nuclear factor of
      activated T cells (NFAT) pathway negatively regulates the activation of Stat5,
      and vice versa in breast cancer. NFAT1 interacts with Stat5 in breast cancer
      cells, and their physical association is mediated by the DNA binding and
      transactivation domains of Stat5. Ectopically expressed NFAT1 is capable of
      inhibiting Stat5-dependent functions, including Stat5 transactivation, Stat5
      mediated transcription of the downstream target gene expression, and binding of
      Stat5a to the Stat5 target promoter. By contrast, overexpression of a selective
      NFAT inhibitor VIVIT reversed NFAT1-mediated suppression of Stat5-dependent gene
      expression, whereas silencing of NFAT1 through RNA interference enhanced
      prolactin-induced, Stat5-mediated gene transcription, and breast cancer cell
      proliferation. A reciprocal inhibitory effect of Stat5 activity on NFAT1
      signaling was also observed, implying these two signaling cascades antagonize
      each other in breast cancer. Importantly, analysis of a matched breast cancer
      progression tissue microarray revealed a negative correlation between levels of
      NFAT1 and Stat5 (pY694) during the progression of breast cancer. Taken together,
      these studies highlight a novel negative cross talk between the NFAT1- and Stat5
      signaling cascades that may affect breast tumor formation, growth, and
      metastasis.

PMID- 21964597
TI  - Interspecies transmission and limited persistence of low pathogenic avian
      influenza genomes among Alaska dabbling ducks.
AB  - The reassortment and geographic distribution of low pathogenic avian influenza
      (LPAI) virus genes are well documented, but little is known about the persistence
      of intact LPAI genomes among species and locations. To examine persistence of
      entire LPAI genome constellations in Alaska, we calculated the genetic identities
      among 161 full-genome LPAI viruses isolated across 4 years from five species of
      duck: northern pintail (Anas acuta), mallard (Anas platyrhynchos), American green
      winged teal (Anas crecca), northern shoveler (Anas clypeata) and American wigeon
      (Anas americana). Based on pairwise genetic distance, highly similar LPAI genomes
      (>99% identity) were observed within and between species and across a range of
      geographic distances (up to and >1000 km), but most often between isolates
      collected 0-10 km apart. Highly similar viruses were detected between years,
      suggesting inter-annual persistence, but these were rare in our data set with the
      majority occurring within 0-9 days of sampling. These results identify LPAI
      transmission pathways in the context of species, space and time, an initial
      perspective into the extent of regional virus distribution and persistence, and
      insight into why no completely Eurasian genomes have ever been detected in
      Alaska. Such information will be useful in forecasting the movement of foreign
      origin avian influenza strains should they be introduced to North America.

PMID- 21964599
TI  - An entropy-based approach for the identification of phylogenetically informative
      genomic regions of Papillomavirus.
AB  - The papillomaviruses form a highly diverse group that infect mammals, birds and
      reptiles. We know little about their genetic diversity and therefore the
      evolutionary mechanisms that drive the diversity of these viruses. Genomic
      sequences of papillomaviruses are highly divergent and so it is important to
      develop methods that select the most phylogenetic informative sites. This study
      aimed at making use of a novel approach based on entropy to select suitable
      genomic regions from which to infer the phylogeny of papillomavirus. Comparative
      genomic analyzes were performed to assess the genetic variability of each gene of
      Papillomaviridae family members. Regions with low entropy were selected to
      reconstruct papillomavirus phylogenetic trees based on four different methods.
      This methodology allowed us to identify regions that are conserved among
      papillomaviruses that infect different hosts. This is important because, despite
      the huge variation among all papillomaviruses genomes, we were able to find
      regions that are clearly shared among them, presenting low complexity levels of
      information from which phylogenetic predictions can be made. This approach
      allowed us to obtain robust topologies from relatively small datasets. The
      results indicate that the entropy approach can successfully select regions of the
      genome that are good markers from which to infer phylogenetic relationships,
      using less computational time, making the estimation of large phylogenies more
      accessible.

PMID- 21964598
TI  - A phylogenetic analysis using full-length viral genomes of South American dengue
      serotype 3 in consecutive Venezuelan outbreaks reveals a novel NS5 mutation.
AB  - Dengue virus currently causes 50-100 million infections annually. Comprehensive
      knowledge about the evolution of Dengue in response to selection pressure is
      currently unavailable, but would greatly enhance vaccine design efforts. In the
      current study, we sequenced 187 new dengue virus serotype 3 (DENV-3) genotype III
      whole genomes isolated from Asia and the Americas. We analyzed them together with
      previously-sequenced isolates to gain a more detailed understanding of the
      evolutionary adaptations existing in this prevalent American serotype. In order
      to analyze the phylogenetic dynamics of DENV-3 during outbreak periods; we
      incorporated datasets of 48 and 11 sequences spanning two major outbreaks in
      Venezuela during 2001 and 2007-2008, respectively. Our phylogenetic analysis of
      newly sequenced viruses shows that subsets of genomes cluster primarily by
      geographic location, and secondarily by time of virus isolation. DENV-3 genotype
      III sequences from Asia are significantly divergent from those from the Americas
      due to their geographical separation and subsequent speciation. We measured amino
      acid variation for the E protein by calculating the Shannon entropy at each
      position between Asian and American genomes. We found a cluster of seven amino
      acid substitutions having high variability within E protein domain III, which has
      previously been implicated in serotype-specific neutralization escape mutants. No
      novel mutations were found in the E protein of sequences isolated during either
      Venezuelan outbreak. Shannon entropy analysis of the NS5 polymerase mature
      protein revealed that a G374E mutation, in a region that contributes to
      interferon resistance in other flaviviruses by interfering with JAK-STAT
      signaling was present in both the Asian and American sequences from the 2007-2008
      Venezuelan outbreak, but was absent in the sequences from the 2001 Venezuelan
      outbreak. In addition to E, several NS5 amino acid changes were unique to the
      2007-2008 epidemic in Venezuela and may give additional insight into the adaptive
      response of DENV-3 at the population level.

PMID- 21964605
TI  - Mutation of the Nrf2 gene in non-small cell lung cancer.
AB  - Nrf2 (NFE2L2) is a transcription factor belonging to the Cap'N'Collar subfamily
      of basic-leucine zipper (bZIP) family of transcription factors, which plays a
      significant role in adaptive responses to oxidative stress. To investigate the
      relationship of between the mutation of Nrf2 gene and non-small cell lung cancer
      (NSCLC), in this study, we sequenced the Nrf2 gene from a total of 103 patients
      with NSCLC and corresponding blood samples. It is found that there is a
      discordance of Nrf2 mutations between NSCLC and corresponding blood samples.
      These differences may indicate that the variants in the Nrf2 gene are associated
      with an increased risk for lung cancer. In addition, the factor of smoking status
      is observed to play important roles in triggering the occurrence of the disorder.

PMID- 21964606
TI  - Endocytosed BCRs sequentially regulate MAPK and Akt signaling pathways from
      intracellular compartments.
AB  - Binding of antigen to the B cell antigen receptor (BCR) triggers both BCR
      signaling and endocytosis. How endocytosis regulates BCR signaling remains
      unknown. Here we report that BCR signaling was not extinguished by endocytosis of
      BCRs; instead, BCR signaling initiated at the plasma membrane continued as the
      BCR trafficked intracellularly with the sequential phosphorylation of kinases.
      Blocking the endocytosis of BCRs resulted in the recruitment of both proximal and
      downstream kinases to the plasma membrane, where mitogen-activated protein
      kinases (MAPKs) were hyperphosphorylated and the kinase Akt and its downstream
      target Foxo were hypophosphorylated, which led to the dysregulation of gene
      transcription controlled by these pathways. Thus, the cellular location of the
      BCR serves to compartmentalize kinase activation to regulate the outcome of
      signaling.

PMID- 21964607
TI  - The carboxypeptidase ACE shapes the MHC class I peptide repertoire.
AB  - The surface presentation of peptides by major histocompatibility complex (MHC)
      class I molecules is critical to CD8(+) T cell-mediated adaptive immune
      responses. Aminopeptidases have been linked to the editing of peptides for MHC
      class I loading, but carboxy-terminal editing is thought to be due to proteasome
      cleavage. By analysis of wild-type mice and mice genetically deficient in or
      overexpressing the dipeptidase angiotensin-converting enzyme (ACE), we have now
      identified ACE as having a physiological role in the processing of peptides for
      MHC class I. ACE edited the carboxyl terminus of proteasome-produced MHC class I
      peptides. The lack of ACE exposed new antigens but also abrogated some self
      antigens. ACE had substantial effects on the surface expression of MHC class I in
      a haplotype-dependent manner. We propose a revised model of peptide processing
      for MHC class I by introducing carboxypeptidase activity into the process.

PMID- 21964608
TI  - A motif in the V3 domain of the kinase PKC-theta determines its localization in
      the immunological synapse and functions in T cells via association with CD28.
AB  - Protein kinase C-theta (PKC-theta) translocates to the center of the
      immunological synapse, but the underlying mechanism and its importance in T cell
      activation are unknown. Here we found that the V3 domain of PKC-theta was
      necessary and sufficient for localization to the immunological synapse mediated
      by association with the coreceptor CD28 and dependent on the kinase Lck. We
      identified a conserved proline-rich motif in V3 required for association with
      CD28 and immunological synapse localization. We found association with CD28 to be
      essential for PKC-theta-mediated downstream signaling and the differentiation of
      T helper type 2 cells (T(H)2 cells) and interleukin 17-producing helper T cells
      (T(H)17 cells) but not of T helper type 1 cells (T(H)1 cells). Ectopic expression
      of V3 sequestered PKC-theta from the immunological synapse and interfered with
      its functions. Our results identify a unique mode of CD28 signaling, establish a
      molecular basis for the immunological synapse localization of PKC-theta and
      indicate V3-based 'decoys' may be therapeutic modalities for T cell-mediated
      inflammatory diseases.

PMID- 21964611
TI  - Bad experiences in the hospital: the stories keep coming.

PMID- 21964610
TI  - Role of mitogen activated protein kinases in skin tumorigenicity of patulin.
AB  - WHO has highlighted the need to evaluate dermal toxicity of mycotoxins including
      Patulin (PAT), detected in several fruits. In this study the skin carcinogenic
      potential of topically applied PAT was investigated. Single topical application
      of PAT (400 nmol) showed enhanced cell proliferation (~2 fold), along with
      increased generation of ROS and activation of ERK, p38 and JNK MAPKs, in mouse
      skin. PAT exposure also showed activation of downstream target proteins, c-fos, c
      Jun and NF-kappaB transcription factors. Further, single topical application of
      PAT (400 nmol) followed by twice weekly application of TPA resulted in tumor
      formation after 14 weeks, indicating the tumor initiating activity of PAT.
      However no tumors were observed when PAT was used either as a complete carcinogen
      (80 nmol) or as a tumor promoter (20 nmol and 40 nmol) for 25 weeks.
      Histopathological findings of tumors found in PAT/TPA treated mice showed that
      these tumors were of squamous cell carcinoma type and similar to those found in
      the positive control group (DMBA/TPA) along with significant increase of lipid
      peroxidation and decrease in free sulfydryls, catalase, superoxide dismutase and
      glutathione reductase activities. The results suggest the possible role of free
      radicals in PAT mediated dermal tumorigenicity involving MAPKs.

PMID- 21964612
TI  - Psychiatry interdisciplinary: the Berlin Congress of Psychiatry.

PMID- 21964609
TI  - Mucosal memory CD8+ T cells are selected in the periphery by an MHC class I
      molecule.
AB  - The presence of immune memory at pathogen-entry sites is a prerequisite for
      protection. Nevertheless, the mechanisms that warrant immunity at peripheral
      interfaces are not understood. Here we show that the nonclassical major
      histocompatibility complex (MHC) class I molecule thymus leukemia antigen (TL),
      induced on dendritic cells interacting with CD8alphaalpha on activated
      CD8alphabeta(+) T cells, mediated affinity-based selection of memory precursor
      cells. Furthermore, constitutive expression of TL on epithelial cells led to
      continued selection of mature CD8alphabeta(+) memory T cells. The memory process
      driven by TL and CD8alphaalpha was essential for the generation of
      CD8alphabeta(+) memory T cells in the intestine and the accumulation of highly
      antigen-sensitive CD8alphabeta(+) memory T cells that form the first line of
      defense at the largest entry port for pathogens.

PMID- 21964613
TI  - A retrospective review of the metabolic syndrome in women diagnosed with breast
      cancer and correlation with estrogen receptor.
AB  - Women diagnosed with obesity and breast cancer have an increased risk of
      recurrence and death (Protani et al., Breast Cancer Res Treat 123:627-635, 1).
      Obesity is associated with the metabolic syndrome--a pathophysiologically
      distinct inflammatory process comprised of central obesity, insulin resistance,
      hypertension, and atherogenic dyslipidemia. The relationship of obesity as a risk
      factor for breast cancer is complex with a protective effect for younger women in
      contrast to a risk for older women (Kabat et al., Cancer Epidemiol Biomarkers
      Prev 18:2046-2053, 2; Ursin et al., Epidemiology 6:137-141, 3). The metabolic
      syndrome has been associated with the risk of cancer, and pro-inflammatory
      circulating factors may be associated with risk of more aggressive breast cancer
      (Capasso et al., Cancer Biol Ther 10:1240-1243, 4; Healy et al., Clin Oncol (R
      Coll Radiol) 22:281-288, 5; Laukkanen et al., Cancer Epidemiol Biomarkers Prev
      13:1646-1650, 6). We conducted a retrospective review of 860 breast cancer
      patients to determine the relationship between estrogen receptor status and the
      metabolic syndrome. We collected the relevant metabolic diagnoses, medications,
      physical findings, and laboratory values and adapted the National Cholesterol
      Education Program criteria to define the metabolic syndrome retrospectively. No
      relationship was found between estrogen receptor status and the individual
      components of the metabolic syndrome. Based on findings in the medical records,
      15% of the women with breast cancer had the metabolic syndrome, and 26% of the
      women were considered obese, 16% hyperglycemic, 54% hypertensive, and 30%
      dyslipidemic. The metabolic syndrome was associated with advanced age and African
      American race (P < 0.001). When adjusted for age, race, and stage, the metabolic
      syndrome was marginally associated with estrogen receptor-positive tumors (P =
      0.054). Our findings do not support the concern that the metabolic syndrome may
      contribute to more biologically aggressive breast cancer.

PMID- 21964615
TI  - Solution processed transition metal sulfides: application as counter electrodes
      in dye sensitized solar cells (DSCs).
AB  - A solution processed method for fabricating transition metal sulfides on fluorine
      doped tin oxide (FTO) as efficient counter electrodes in iodine/iodide based
      solar cells has been demonstrated. Conversion efficiencies of 7.01% and 6.50%
      were obtained for nickel and cobalt sulfides, respectively, comparable to the
      conventional thermally platinised FTO electrodes (7.32%). A comparable charge
      transfer resistance of Ni(3)S(2) and Co(8.4)S(8) to conventional Pt was found to
      be a key factor for such high efficiencies. Cyclic voltammetry, Kelvin probe
      microscopy, Electrochemical Impedance Spectroscopy, and Tafel polarization were
      performed to study the underlying reasons behind such efficient counter electrode
      performance.

PMID- 21964614
TI  - Chronic dichlorvos exposure: microglial activation, proinflammatory cytokines and
      damage to nigrostriatal dopaminergic system.
AB  - Dopaminergic cells in the substantia nigra are highly vulnerable to the
      neurodegenerative process of Parkinson's disease. Therefore, mechanisms that
      enhance their susceptibility to injury bear important implications for disease
      pathogenesis. We have previously shown that chronic dichlorvos exposure caused
      nigrostriatal dopaminergic degeneration and significant behavioral impairments.
      In this study, we analyzed the relationship between microglial activation and
      dopaminergic neurodegeneration to examine the possibility that neuroinflammation
      may induce dopaminergic neuronal loss in the nigrostriatal system. Chronic
      dichlorvos exposure causes microglial activation including induction of NADPH
      oxidase and a selective loss of dopaminergic neurons in rat. Microglial marker
      expression was increased at transcription as well as translational levels in the
      substantia nigra (SN) and corpus striatum (CS) of rats exposed to dichlorvos.
      Activated microglia were seen in SN and CS of dichlorvos-treated animals but were
      rarely observed in controls. Immunostaining revealed lesser number of TH-positive
      neurons and higher number of microglia in SN and CS regions after dichlorvos
      treatment. The mRNA and protein levels of the NADPH oxidase main subunit
      gp91(phox) were significantly increased after dichlorvos administration.
      Dichlorvos exposure also leads to increased level of microglial noxious mediators
      such as IL-1beta, TNF-alpha and IL-6 in ventral midbrain and CS at transcription
      as well as translational levels. Data indicate that microglial activation and
      consequent induction of NADPH oxidase and proinflammatory cytokines such as TNF
      alpha, IL-1beta and IL-6 may act as risk factors for Parkinson's disease by
      increasing the vulnerability of dopaminergic cells to dichlorvos toxic injury.

PMID- 21964616
TI  - Effects of albumin-bound-fatty acids on the growth of the human T lymphoblastic
      cell line Jurkat.

PMID- 21964617
TI  - Development of a novel quantitative real-time assay using duplex mutation primers
      for rapid detection of Candida species.
AB  - We developed a novel quantitative real-time PCR for quantitating Candida DNA
      based on the duplex mutation primer principle, in which a signal is generated by
      melting a duplex mutation primer during renaturation. The duplex mutation primers
      are much more specific than double-stranded DNA dyes such as SYBR-Green I and,
      unlike other probes, do not require the double-labeled synthesis of fluorophore
      and a quencher on the same molecule. A total of 176 clinical blood specimens were
      obtained from patients hospitalized in our hospital with clinically proven or
      suspected systemic Candida infection. The presence of DNA from pathogens in the
      Candida species was detected using real-time PCR targeting of an internal
      transcribed spacer region of a fungal gene. The assay exhibited a low limit of
      detection (10 CFU/ml of blood), an excellent reproducibility and specificity.
      Twenty-eight positive samples exhibited a wide range of Candida species loads,
      extending from 13 to 90,528 CFU/ml of blood. The sensitivity and specificity of
      the present assay were 100 and 97.4%, respectively, compared with the results of
      blood culture. Our data suggest that this assay may be appropriate for use in
      clinical laboratories as a simple, low-cost and rapid screening test for the most
      frequently encountered Candida species.

PMID- 21964618
TI  - A randomized, double-blind, placebo-controlled trial of misoprostol for oral
      mucositis secondary to high-dose chemotherapy.
AB  - PURPOSE: Misoprostol, a synthetic analog of prostaglandin E1, has anti
      inflammatory and mucosa-protecting properties. The objective of this study was to
      evaluate the efficacy of misoprostol oral rinse in reducing the severity of oral
      mucosal injury caused by high-dose chemotherapy. METHODS: The study used a
      randomized, double-blind, placebo-controlled, parallel-group design. Oncology
      patients receiving myeloablative high-dose chemotherapy, in preparation for a
      hematopoietic stem cell transplant, were randomized to misoprostol or placebo
      rinse. The primary outcome measure was the severity of oral mucositis, measured
      using the modified Oral Mucositis Index. Additional outcome measures included the
      severity of mouth pain (measured using a Visual Analog Scale and the Pain Affect
      Faces Scale), duration of hospital stay, and days on total parenteral nutrition.
      RESULTS: This study was originally planned to accrue 160 subjects but was
      terminated early due to revised sponsor research priorities. The intent-to-treat
      population consisted of 22 subjects randomized to misoprostol rinse and 26
      subjects randomized to placebo rinse. There was no significant difference between
      the two groups in mucositis or pain severity. In both groups, duration of
      hospital stay was approximately 19 days, and number of days on total parenteral
      nutrition was 17-18 days. There were no serious adverse events attributable to
      misoprostol rinse. CONCLUSIONS: Although this study did not find a beneficial
      effect of a misoprostol rinse in mucositis secondary to high-dose chemotherapy,
      the small sample size limits the strength of this conclusion. Given the proposed
      importance of the prostaglandin pathway in the pathogenesis of oral mucositis,
      additional studies are warranted.

PMID- 21964619
TI  - Role of antioxidants in buccal mucosa cells and plasma on the incidence and
      severity of oral mucositis after allogeneic haematopoietic cell transplantation.
AB  - PURPOSE: Oral mucositis (OM) is known to be a significant complication of
      chemotherapy preceding haematopoietic cell transplantation (HCT). Antioxidants
      (AOX) scavenge free radicals, which play a major role in the initiation of OM and
      may reduce the OM risk. STUDY DESIGN: The primary objective of this prospective
      study was to investigate the association between the incidence and severity of OM
      (WHO oral toxicity scale) and the AOX status in buccal mucosa cells (BMC) and
      plasma. The alpha-tocopherol, ascorbic acid and beta-carotene concentrations in
      BMC and plasma were assessed at admission in 70 patients with a median age of 58
      years before undergoing allogeneic HCT. RESULTS: Severe OM (III-IV), ulcerative
      OM (II-IV) and no or mild OM (0-I) were documented in 14 (20.0%), 32 (45.7%) and
      38 (54.3%) patients, respectively. We observed no significant differences in
      baseline AOX concentrations in plasma or BMC among the OM groups. However,
      between patients with at least one plasma AOX beneath the normal range (39/70)
      and those with all plasma AOX in the normal range (31/70), we noted a trend
      towards longer duration of parenteral nutrition (PN) during the study period (10
      vs. 8 days; p = 0.066). CONCLUSIONS: No single AOX, either in plasma or BMC
      (alpha-tocopherol, ascorbic acid and beta-carotene), revealed predictive value
      for the incidence or severity of OM. However, patients with an overall good
      plasma AOX status tended to require less PN, a common clinical marker for OM,
      which may be more relevant than any one AOX at reducing the risk of OM.

PMID- 21964620
TI  - Fusion of imaging technologies: how, when, and for whom?
AB  - Over the past decade, electroanatomic mapping has emerged as a useful tool for
      complex ablation procedures. A more recent advancement is the development of
      image integration. Image integration refers to the process of registering a
      previously acquired MRI or CT scan of the heart with the mapping space during the
      ablation procedure. The technique of image integration is now relied on by many
      electrophysiology laboratories to guide complex ablation procedures, particularly
      atrial fibrillation ablation and ablation of patients with ventricular
      tachycardia in the setting of structural heart disease. An even more recent
      development is image fusion. This refers to taking information about the
      myocardial substrate, especially intramyocardial scar, and registering it with
      the active mapping space. This technique remains in its infancy but shows great
      promise in facilitating complex ablation procedures. The purpose of the article
      is to review the development, state of the art, and future of these image
      integration and fusion techniques.

PMID- 21964622
TI  - Laser Florence 2011. Abstracts of the 25th International Congress Laser Medicine
      & IALMS Courses, jointly with the Congress of the International Phototherapy
      Association. November 4-5, 2011. Florence, Italy.

PMID- 21964621
TI  - The impact of antimicrobial photodynamic therapy in an artificial biofilm model.
AB  - The susceptibility of bacterial cultures in biofilm formations is important for a
      variety of clinical treatment procedures. Therefore, the aim of the study was to
      assess the impact of laser-induced antimicrobial photodynamic therapy on the
      viability of Streptococcus mutans cells employing an artificial biofilm model.
      Using sterile chambered coverglasses, a salivary pellicle layer was formed in 40
      chambers. Streptococcus mutans cells were inoculated in a sterile culture medium.
      Employing a live/dead bacterial viability kit, bacteria with intact cell
      membranes stained fluorescent green. Each pellicle-coated test chamber was filled
      with 0.7 ml of the bacterial suspension and analysed using a confocal laser
      scanning microscope within a layer of 10 MUm at intervals of 1 MUm from the
      pellicle layer. Phenothiazine chloride was used as a photosensitizer in all 40
      test chambers. A diode laser (wavelength 660 nm, output power 100 mW) was used to
      irradiated 20 chambers for 2 min. Fluorescence values in the test chambers after
      laser irradiation (median 2.1 U, range 0.4-3.4 U) were significantly lower than
      baseline values after adding the photosensitizer (median 3.6 U, range 1.1-9.0; p
      < 0.05). The non-irradiated control chambers showed no change in fluorescence at
      the end of an additional photosensitizer residence time of 2 min without laser
      irradiation (median 1.9 U, range 0.7-3.6; median 1.9 U, range 0.8-6.0,
      respectively; p > 0.05). The present study indicated that laser irradiation is an
      essential part of antimicrobial photodynamic therapy to reduce bacteria within a
      layer of 10 MUm. Further studies are needed to evaluate the maximum biofilm
      thickness that still allows a toxic effect on microorganisms.

PMID- 21964623
TI  - The first reported case of canine subcutaneous Cryptococcus flavescens infection.
AB  - This report describes the first documented case of subcutaneous infection due to
      Cryptococcus flavescens in a dog. The chief symptoms of the patient dog were
      abscessed lesions on the dorsal muzzle, right eyelid, and lower jaw. Biopsy
      specimens from the lesions on the dorsal muzzle and lower jaw showed
      pyogranulomatous inflammation with numerous yeast cells. The patient dog was
      diagnosed with a subcutaneous fungal infection and orally received 5 mg/kg
      itraconazole once a day for 2 months, the abscesses disappeared. After 1 month at
      the end of treatment, the skin lesions did not redevelop. Isolates from the
      biopsy specimens were identified as C. flavescens by molecular analysis as well
      as morphologic and biochemical examination, indicating that C. flavescens is a
      potential canine pathogen.

PMID- 21964624
TI  - Cutaneous protothecosis in patient with diabetes mellitus and review of published
      case reports.
AB  - Protothecosis is an opportunistic infection caused by Prototheca, usually called
      as saprophytes, and is frequently found in natural and living surroundings with
      low virulence, but may cause chronic infection in immunocompromised individuals.
      We report a case of cutaneous protothecosis with zopfii var. portoricensis
      infection in a 66-year-old diabetic woman following hand surgery on middle right
      finger. Mycology study showed that smooth, creamy white, yeast-like colonies
      grown after necrotic tissue was cultured on Sabouraud dextrose agar at both 37
      and 25 degrees C. The organism was then identified as Prototheca zopfii var.
      portoricensis by molecular identification and also found from histopathology of
      the lesion. The lesion got improved with intravenous amphotericin B and
      itraconazole.

PMID- 21964625
TI  - Pulmonary arterial systolic pressure and susceptibility to high altitude
      pulmonary edema.
AB  - There is evidence that pulmonary arterial hypertension plays a major role in the
      occurrence of high altitude pulmonary edema (HAPE). We tested the hypothesis that
      the pulmonary arterial systolic pressure response to a challenge associated with
      hypoxia and mild exercise may be considered a predictive factor of HAPE.
      Pulmonary arterial systolic pressure was measured by Doppler echocardiography in
      8 HAPE susceptible (HAPE-S) subjects and 8 HAPE resistant mountaineers (HAPE-R)
      during a hypoxic exercise challenge established by the French Association for
      Sport Medicine (Richalet's test). Pulmonary arterial systolic pressure during
      hypoxic exercise allowed a significant discrimination between the groups,
      although an overlap of values was observed. When expressed as individual
      variations from baseline to hypoxic exercise level however, we found a highly
      significant difference. No overlap was observed between HAPE-R (range: 6.7-18.5
      mmHg) and HAPE-S (range: 19.2-30.4 mmHg) groups, with a cut-off value at 19 mmHg.
      Plasma Vascular Endothelial growth factor (VEGF) and malondialdehyde (MDA)
      increased in response to hypoxic exercise only in HAPE-S group. Individual
      increases in pulmonary arterial systolic pressure during hypoxic exercise from
      basal resting normoxic values seem relevant to estimate HAPE susceptibility when
      measured during the Richalet's test.

PMID- 21964627
TI  - Interpretation and implications of the prematurely terminated Stenting and
      Aggressive Medical Management for Preventing Recurrent Stroke in the Intracranial
      Stenosis (SAMMPRIS) trial.

PMID- 21964628
TI  - Saharan dust episodes and pregnancy.
AB  - Desert dust is one of the natural contributors to atmospheric particulate matter
      worldwide. Although particulate pollution has been shown to adversely affect
      pregnancy, the available evidence on the impact of dust episodes on pregnancy is
      very scarce. The aim of this study was to evaluate the impact of Saharan dust
      episodes on pregnancy complications (preeclampsia and bacteriuria) and outcomes
      (birth weight and gestational age at delivery). This study was based on a cohort
      of births (N = 3565) that occurred in a major university hospital in Barcelona
      during 2003-2005. To determine Saharan dust episodes, we developed a two-stage
      approach based on meteorological evidence of the presence of Saharan dust cloud
      over the region and unusually high levels of particulate levels on the ground
      while taking account of traffic sources. The associations between the number of
      Saharan dust episodes during whole pregnancy as well as each pregnancy trimester
      and pregnancy complications and outcomes were analysed. There were 152 days (out
      of 838 days) with Saharan dust cloud over the region from which 45 days were
      determined as episodic days. We did not observe any statistically significant
      harmful effect of Saharan dust episodes on our included pregnancy complications
      and outcomes. However, we observed a small but statistically significant increase
      in gestational age at delivery in association with the number of episodic days
      during the third trimester and whole pregnancy (0.8 and 0.5 days respectively).
      Our findings were not suggestive for any adverse effect of Saharan dust episodes
      on our included pregnancy complications and outcomes.

PMID- 21964629
TI  - Manganese-enhanced MRI reveals multiple cellular and vascular layers in normal
      and degenerated retinas.
AB  - PURPOSE: To use manganese-enhanced magnetic resonance imaging (MEMRI) at 25 * 25
      * 800 MUm(3) to image different retinal and vascular layers in the rat retinas.
      MATERIALS AND METHODS: Manganese-chloride was injected intraocularly in normal (n
      = 5) and Royal College of Surgeons (RCS, an model of photoreceptor degeneration)
      (n = 5) rats at postnatal day 90. MEMRI at 4.7 T was performed 24 hours later.
      MRI was repeated following intravenous Gd-DTPA in the same animals to highlight
      the vasculatures. Layer assignment and thickness were compared to histology.
      RESULTS: MEMRI 24 hours after intravitreal manganese-chloride injection revealed
      seven bands of alternating hyper- and hypointensities, corresponding
      histologically to the ganglion cell layer, inner plexiform layer, inner nuclear
      layer, outer plexiform layer, outer nuclear layer, photoreceptor-segment layer,
      and choroidal vascular layer. Intravenous Gd-DTPA-which does not cross the blood
      retinal barrier and the retinal pigment epithelium-further enhanced the two
      layers bounding the retina, corresponding to the retinal and choroidal vascular
      layers, but not the avascular outer nuclear layer and the photoreceptor-segment
      layer. MEMRI of the RCS retinas revealed the loss of the outer plexiform layer,
      outer nuclear layer, and photoreceptor-segment layer. Histological analysis
      corroborated the MRI laminar assignments and thicknesses. CONCLUSION: Lamina
      specific retinal structures neurodegenerative changes to structure in retinal
      diseases can be detected using MEMRI.

PMID- 21964630
TI  - Seasonality of brown recluse spiders, Loxosceles reclusa, submitted by the
      general public: implications for physicians regarding loxoscelism diagnoses.
AB  - Many medically important animals exhibit fluctuating seasonal abundance such that
      risk from envenomation or disease is not constant throughout the year. As
      indicated by homeowner submissions, brown recluse spiders, Loxosceles reclusa,
      show seasonal peaks of activity during summer and paucity in winter. This
      information should be incorporated as part of the diagnostic algorithm for
      physicians when considering the probability of loxoscelism in endemic Loxosceles
      areas especially if a skin lesion occurs when spiders are scarce.

PMID- 21964631
TI  - Novel cytotoxicity associated with Anabaena circinalis 131C.
AB  - The production of secondary metabolites by cyanobacteria is extensively varied.
      Anabaena spp. have been shown to produce the toxins saxitoxin, anatoxin-a,
      anatoxin-a(s), cylindrospermopsin and microcystin. In this study we show
      cytotoxicity associated with Anabaena circinalis 131C that could not be
      attributed to its high saxitoxin content. Analytical, ELISA and enzymatic methods
      excluded the presence of other known cyanobacterial toxins leading to the
      suggestion of novel toxicity.

PMID- 21964633
TI  - Effects of 4-tert-butylpyridine on the quasi-Fermi levels of TiO2 films in the
      presence of different cations in dye-sensitized solar cells.
AB  - The effects of additives on the quasi-Fermi levels (QFL) of TiO(2) films in dye
      sensitized solar cells (DSCs) were investigated by a direct method. We observed
      that the values of QFL of TiO(2) at short circuit and open circuit are different
      and found for the first time the linear relationships between QFL shifts at short
      circuit and open circuit induced by 4-tert-butylpyridine (TBP), and that the
      slopes of the lines were significantly influenced by the nature of cations in the
      electrolyte. Different QFL shifts at short circuit and open circuit were observed
      in the presence of TBA(+). These quantitative results suggest that the QFL of
      TiO(2) films at short circuit and open circuit can be adjusted separately by
      developing suitable additives and cations, which will be helpful to further
      improve the efficiency of DSCs.

PMID- 21964632
TI  - TRP channel antagonists as potential antitussives.
AB  - Cough is a troublesome symptom associated with many respiratory diseases. In some
      instances cough can become prolonged and excessive, and chronic cough of various
      aetiologies is a common presentation to specialist respiratory clinics. However,
      current treatment options are limited. Despite its importance, our understanding
      of the mechanisms that provoke cough is poor. Recent investigation has focused on
      the interaction between G-protein-coupled receptors and ion channels expressed on
      airway sensory nerves that are responsible for driving the cough reflex. In
      particular, the Transient Receptor Potential class of ion channels appears to
      play a major role as a regulator of the afferent arm of the cough reflex and
      could be involved in the heightened cough response observed in disease states.
      Current research investigating the pathogenesis of cough supports the development
      of TRP channel inhibitors as novel and selective treatment modalities.

PMID- 21964634
TI  - High incidence of acute promyelocytic leukemia specifically induced by N-nitroso
      N-methylurea (NMU) in Sprague-Dawley rats.
AB  - Carcinogenic agents such as N-methyl-N-nitrosourea can cause tumors. The aims of
      the present study were to evaluate and classify a subtype of AML (acute myeloid
      leukemia) that was induced by NMU. According to previous publications, NMU
      induces not only mammary cancer but also leukemia in Sprague-Dawley (S-D) rats.
      However, the subtype of leukemia involved in NMU-treated rats is unknown. We
      found that both organ weight and relative organ weights were significantly higher
      in NMU-exposed rats than in controls. Morphological changes of rat livers and
      spleens were assessed by histological evaluation (H&E staining), which found that
      these tissues were abnormal in appearance. Also, cytological examination of the
      blood showed immature white blood cells in a smear using Liu's and Papanicolaou
      stains, indicating that gross abnormalities and histopathological changes were
      pathologically observed. NMU leukemia incidence was 97.1%. In this study,
      immunohistochemical (IHC) analysis was valuable in classifying the leukemia of
      poorly differentiated blasts induced by NMU. Paraffin blocks were stained for
      MPO, CD3, CD15, CD20, and CD34 markers. The NMU-induced group was positive for
      MPO, but negative for CD3, CD15, CD20, and CD34. These CD markers suggest that
      they are useful in helping diagnose APL (M3) leukemia. The model of NMU-induced
      leukemogenesis in an S-D rat suggests a more definite way to classify APL. This
      APL will provide an important tool for chemical carcinogenesis and leukemia
      studies.

PMID- 21964635
TI  - Fisetin induces apoptosis in human cervical cancer HeLa cells through ERK1/2
      mediated activation of caspase-8-/caspase-3-dependent pathway.
AB  - Fisetin is a naturally occurring flavonoid that has been reported to inhibit the
      proliferation and to induce apoptotic cell death in several tumor cells. However,
      the apoptosis-inducing effect of fisetin on tumor cell lines was investigated
      besides HeLa cells. In this study, we found that fisetin induced apoptosis of
      HeLa cells in a dose- and time-dependent manner, as evidenced by nuclear staining
      of 4'-6-Diamidino-2-phenylindole (DAPI), flow cytometry assay, and Annexin-V/PI
      double-labeling. In addition, fisetin triggered the activations of caspases-3 and
      -8 and the cleavages of poly (ADP-ribose) polymerase, resulting in apoptosis
      induction. Moreover, treatment of HeLa cells with fisetin induced a sustained
      activation of the phosphorylation of ERK1/2, and inhibition of ERK1/2 by PD98059
      (MEK1/2 inhibitor) or transfection with the mutant ERK1/2 expression vector
      significantly abolished the fisetin-induced apoptosis through the activation of
      caspase-8/-3 pathway. The in vivo xenograft mice experiments revealed that
      fisetin significantly reduced tumor growth in mice with HeLa tumor xenografts. In
      conclusion, our results indicated that fisetin exhibited anti-cancer effect and
      induced apoptosis in HeLa cell lines both in vitro and in vivo.

PMID- 21964636
TI  - Inhibition of autophagy by 3-methyladenine protects 1321N1 astrocytoma cells
      against pyocyanin- and 1-hydroxyphenazine-induced toxicity.
AB  - Central nervous system (CNS) infections due to Pseudomonas aeruginosa are
      difficult to treat and have a high mortality rate. Pyocyanin, a virulence factor
      produced by P. aeruginosa, has been shown to be responsible for the majority of
      P. aeruginosa's pathogenicity in mammalian cells. Several lines of evidence in
      respiratory cells suggest that this damage is primarily mediated by pyocyanin's
      ability to generate ROS and deplete host antioxidant defense mechanisms. However,
      it has yet to be established whether pyocyanin or 1-hydroxyphenazine have
      potential toxicity to the CNS. Therefore, the aim of this study was to compare
      the CNS toxicity of pyocyanin and 1-hydroxyphenazine in vitro and to provide
      insight into mechanisms that underlie this toxicity using 1321N1 astrocytoma
      cells. To achieve this, we investigated the contribution of oxidative stress and
      other mediators of cell death including autophagy, senescence and apoptosis. We
      show that oxidative stress is not a primary mediator of pyocyanin (0-100 MUM) and
      1-hydroxyphenazine (0-100 MUM) induced toxicity in 1321N1 cells. Instead, our
      results suggest that autophagy may play a central role. The autophagy inhibitor 3
      methyladenine (5 mM) protected 1321N1 astrocytoma cells against both pyocyanin
      and 1-hydroxyphenazine-induced cell injury and increased accumulation of acidic
      vesicular organelles, a hallmark of autophagy. Furthermore, apoptosis and
      senescence events may be secondary to autophagy in pyocyanin and 1
      hydroxyphenazine-mediated cell injury. In conclusion, this study provides the
      first evidence on mechanisms underlying the toxicity of both pyocyanin and 1
      hydroxyphenazine to astrocytoma cells and provides novel evidence suggesting that
      this toxicity may be mediated by the formation of acidic vesicular organelles, a
      hallmark of autophagic cell death.

PMID- 21964637
TI  - The unregulated commercialization of stem cell treatments: a global perspective.
AB  - Research into the biological properties and clinical potential of stem cells has
      spurred strong public investment, industry development, media coverage, and
      patient interest in recent years. To date, however, few clinical applications of
      demonstrated safety and efficacy have been developed with the exception of uses
      of hematopoietic stem cells in the treatment of diseases of the blood and immune
      systems. This lack of an evidence basis notwithstanding, hundreds of companies
      and private clinics around the world now sell putative stem cell treatments for
      an enormously broad range of medical and quality-of-life conditions. This
      represents a major challenge for legitimate scientists working in the field, for
      authorities seeking to protect their constituencies, and for patients and
      consumers targeted by such companies' marketing strategies. In this review, I
      provide an overview of the global industry in pseudomedical stem cell treatments,
      with an investigation of claims in a single disease area (amyotrophic lateral
      sclerosis), and make recommendations for the introduction and enforcement of
      appropriate regulatory responses to this problem.

PMID- 21964639
TI  - Regional functional recovery after acute myocardial infarction: a cardiac
      magnetic resonance long-term study.
AB  - We sought to analyze the trend of functional recovery after successful reperfused
      ST-elevation myocardial infarction (STEMI) in an optimally treated patient group
      over a 14 month follow-up in relation to ischemia-time and the presence of
      microvascular obstruction (MVO). First-pass perfusion-, cine- and late
      enhancement (LE)- cardiac MR were performed in 40 patients (33 male and 7 female,
      54.8 +/- 12.3 years) within 6 days as well as 4 and 14 months after successful
      primary percutaneous coronary intervention for STEMI. Significant recovery of
      segmental wall thickening (SWT %) occurred exclusively in infarcted segments
      reperfused within 4 h after symptom onset (group 1 with pain-to-balloon time <2
      h: 59 +/- 4 to 70 +/- 4%; P < 0.02) (group 2 with pain-to-balloon-time 2-4 h: 51
      +/- 4 to 59 +/- 3%, P < 0.05) during the first 4 months, whereas changes
      thereafter were not significant (P = NS). Infarcted segments with MVO showed
      lowest regional myocardial function at any time of assessment (all P < 0.001) and
      a lack of significant recovery during the study period. Significant recovery of
      regional myocardial function is related to rapid revascularization of the infarct
      related artery and the absence of MVO. Improvement of SWT occurred exclusively
      within the first 4 months after acute myocardial infarction and remained
      unchanged thereafter.

PMID- 21964638
TI  - Long-term follow-up of cardiac resynchronization therapy: mechanical
      resynchronization and reverse left ventricular remodeling are predictive for long
      term transplant-free survival.
AB  - We sought to determine whether correction of mechanical left ventricular (LV)
      dyssynchrony as defined by tissue Doppler imaging (TDI) is predictive for
      transplant-free long-term survival in patients (pts.) undergoing cardiac
      resynchronization therapy (CRT). In 76 CRT recipients TDI curves from the septal,
      lateral, anterior, and inferior basal LV were obtained at baseline and after 6 +/
      4 months. A time difference between regional electromechanical delays (EMD) of
      >=40 ms was considered dyssynchronous. At follow-up, pts. were classified as TDI
      responders (TDI-R: dyssynchrony at baseline, corrected by CRT) versus non
      responders (TDI-NR: either not dyssynchronous at baseline, or persisting
      dyssynchrony). Pts. were then followed by standard echocardiography over 21 +/- 6
      months and were re-classified as LV remodelers (LV-R: LV volume reduction of
      >10%) versus non-remodelers (LV-NR). The end-point during clinical long-term
      follow-up of 65 +/- 38 months was all-cause mortality or heart transplantation.
      44 out of the 76 pts. (58%) were classified as TDI-R, 32 (42%) as TDI-NR.
      Significant reverse LV remodeling was observed in 41 (54%) pts., while 35 (46%)
      did not improve LV size and function. TDI-R was associated with LV-R in 35 pts.
      (85%; P < 0.001). During long-term follow-up, 38 pts. (50%) reached the end
      point, 11 (30%) in the TDI-R group, and 27 (70%) in the TDI-NR group (P <
      0.0003). Mechanical resynchronization as defined by TDI translates into a
      significant survival benefit in CRT recipients.

PMID- 21964640
TI  - Penicillin: the medicine with the greatest impact on therapeutic outcomes.
AB  - The principal point of this paper is that the discovery of penicillin and the
      development of the supporting technologies in microbiology and chemical
      engineering leading to its commercial scale production represent it as the
      medicine with the greatest impact on therapeutic outcomes. Our nomination of
      penicillin for the top therapeutic molecule rests on two lines of evidence
      concerning the impact of this event: (1) the magnitude of the therapeutic
      outcomes resulting from the clinical application of penicillin and the subsequent
      widespread use of antibiotics and (2) the technologies developed for production
      of penicillin, including both microbial strain selection and improvement plus
      chemical engineering methods responsible for successful submerged fermentation
      production. These became the basis for production of all subsequent antibiotics
      in use today. These same technologies became the model for the development and
      production of new types of bioproducts (i.e., anticancer agents, monoclonal
      antibodies, and industrial enzymes). The clinical impact of penicillin was large
      and immediate. By ushering in the widespread clinical use of antibiotics,
      penicillin was responsible for enabling the control of many infectious diseases
      that had previously burdened mankind, with subsequent impact on global population
      demographics. Moreover, the large cumulative public effect of the many new
      antibiotics and new bioproducts that were developed and commercialized on the
      basis of the science and technology after penicillin demonstrates that penicillin
      had the greatest therapeutic impact event of all times.

PMID- 21964641
TI  - Overproduction and secretion of alpha-ketoglutaric acid by microorganisms.
AB  - This mini-review presents a summary of research results of biotechnological
      production of alpha-ketoglutaric acid (KGA) by bacteria and yeasts. KGA is of
      particular industrial interest due to its broad application scope, e.g., as
      building block chemical for the chemical synthesis of heterocycles, dietary
      supplement, component of infusion solutions and wound healing compounds, or as
      main component of new elastomers with a wide range of interesting mechanical and
      chemical properties. Currently KGA is produced via different chemical pathways,
      which have a lot of disadvantages. As an alternative several bacteria and yeasts
      have already been studied for their ability to produce KGA as well as for
      conditions of overproduction and secretion of this intermediate of the
      tricarboxylic acid cycle. The aim of this mini-review was to summarize the known
      data and to discuss the potentials of biotechnological processes of KGA
      production.

PMID- 21964642
TI  - Prevalence and correlates of symptoms and uncertainty in illness among head and
      neck cancer patients receiving definitive radiation with or without chemotherapy.
AB  - PURPOSE: This repeated measures, prospective study was designed to explore and
      describe symptom dimensions, depressive symptoms, and uncertainty in newly
      diagnosed oropharyngeal and laryngeal cancer patients during and 1 month
      following treatment. MATERIALS AND METHODS: A non-probability sample of 21
      oropharyngeal and laryngeal cancer patients receiving definitive radiation
      completed the Memorial Symptom Assessment Scale, Beck Depression Inventory, and
      Mishel's Uncertainty in Illness Scale at treatment initiation, and at 5, 9, and
      12 weeks. RESULTS: A common pattern of 11 symptoms, which changed as treatment
      progressed, was problematic for patients. Physical symptoms increased by 50% at
      week 5 and 9. Depression was experienced by 24% of patients. Uncertainty was
      found to be high at all time points and unexpectedly remained unchanged over time
      (p = 0.73). Positive correlations (p < 0.05) were found among number of symptoms,
      symptom distress, and depressive symptoms. Uncertainty was correlated (p < 0.05)
      statistically only to symptom distress. CONCLUSION: This study is the first to
      identify uncertainty in illness among oropharyngeal and laryngeal cancer patients
      and found it to be higher than for other cancer populations. Findings provide
      insights into the uncertainty of living through treatment and provide information
      for patient care. The consistent pattern of high levels of uncertainty during and
      1 month after treatment suggests that the uncertainty related to acute illness
      could extend into chronic uncertainty which may interfere with a cancer
      survivor's adaption to daily living after treatment. Further research is needed
      to investigate other variables that influence uncertainty during treatment as
      well as 1 to 6 months after treatment for head and neck cancer.

PMID- 21964643
TI  - Is conflict monitoring supramodal? Spatiotemporal dynamics of cognitive control
      processes in an auditory Stroop task.
AB  - The electrophysiological correlates of conflict processing and cognitive control
      have been well characterized for the visual modality in paradigms such as the
      Stroop task. Much less is known about corresponding processes in the auditory
      modality. Here, electroencephalographic recordings of brain activity were
      measured during an auditory Stroop task, using three different forms of
      behavioral response (overt verbal, covert verbal, and manual), that closely
      paralleled our previous visual Stroop study. As was expected, behavioral
      responses were slower and less accurate for incongruent than for congruent
      trials. Neurally, incongruent trials showed an enhanced fronto-central negative
      polarity wave (N(inc)), similar to the N450 in visual Stroop tasks, with similar
      variations as a function of behavioral response mode, but peaking ~150 ms
      earlier, followed by an enhanced positive posterior wave. In addition, sequential
      behavioral and neural effects were observed that supported the conflict
      monitoring and cognitive adjustment hypothesis. Thus, while some aspects of the
      conflict detection processes, such as timing, may be modality dependent, the
      general mechanisms would appear to be supramodal.

PMID- 21964644
TI  - Prevalence of insulin resistance and impaired glucose tolerance in a sample of
      obese Spanish children and adolescents.
AB  - The prevalence of obesity in children has increased in developed countries in the
      last decades. It is associated with alterations in glucose metabolism that may be
      present in childhood. To assess the frequency of glucose metabolism alterations
      and insulin resistance and their possible determinants in a sample of obese
      children from Valladolid (Spain), we retrospectively studied 100 obese children
      and adolescents (11.59 +/- 2.73 years). Anthropometric measures, biochemical
      parameters, and oral glucose tolerance test (OGTT) were performed. Insulin
      resistance was evaluated with fasting insulin, HOMA index, and insulin values in
      OGTT. Impaired glucose tolerance was found in 15% of the sample, and was the most
      frequent of glucose metabolism alterations. Impaired fasting glucose was found in
      2%. No case of type 2 diabetes was found. Acanthosis nigricans was present in
      22%, with predominance in females, but not all presented insulin resistance. The
      prevalence of insulin resistance was 29% when HOMA index was used, and 50% when
      the insulin response in OGTT was used. Not all patients with impaired glucose
      tolerance had a pathological HOMA index, and not all with pathological HOMA index
      presented insulin resistance when insulin values in OGTT were used. Higher 2-h
      post-OGTT insulin levels were found in children with impaired glucose tolerance.
      It is paramount to identify young people with glucose regulation alterations for
      early, intensive intervention to prevent or at least postpone the onset of type 2
      diabetes. OGTT is a screening tool necessary to fulfill this objective.

PMID- 21964646
TI  - Hypoxia-induced increases in A549/CDDP cell drug resistance are reversed by RNA
      interference of HIF-1alpha expression.
AB  - This study aimed to investigate the effects of knocking down hypoxia-inducible
      factor-1alpha (HIF-1alpha) through RNA interference on hypoxia-induced increases
      in drug resistance in A549/CDDP cells, and to study the underlying mechanisms. A
      small interfering RNA (siRNA) eukaryotic expression vector targeting HIF-1alpha
      was constructed and transfected into A549/CDDP cells treated with hypoxia. The
      mRNA and protein levels of HIF-1alpha, multidrug resistance-1 (MDR1), and
      multidrug resistance-associated protein (MRP) were determined by reverse
      transcription polymerase chain reaction (RT-PCR) and immunocytochemistry. Cell
      viability following treatment with cisplatin was determined by MTT assay. Hypoxia
      increased the resistance of A549/CDDP cells to cisplatin and this effect was
      reversed by the siRNA inhibition of HIF-1alpha expression. Expression of HIF
      1alpha siRNA also downregulated HIF-1alpha, MDR1 and MRP mRNA, and protein
      expression in A549/CDDP cells treated with hypoxia (p<0.05). Hypoxia-induced
      resistance of A549/CDDP cells to cisplatin is reversed by the siRNA inhibition of
      HIF-1alpha expression. This effect may be mediated by a decreased expression of
      MDR1 and MRP.

PMID- 21964645
TI  - Role of serum FSH measurement on bone resorption in postmenopausal women.
AB  - In vitro and animals models have shown follicle-stimulating hormone (FSH) effects
      on osteoclastic function, and FSH levels seem to influence bone loss
      independently of estrogen concentrations in humans. Our aim was to evaluate the
      role of serum FSH measurement in the assessment of bone resorption in
      postmenopausal women. We conducted a cross-sectional study including 92
      postmenopausal healthy women aged 56.2 (3.6) and 7.2 (4) years since menopause.
      Serum FSH, luteinizing hormone (LH), estradiol (E2) and bone turnover markers as
      osteocalcin (OC) and C-terminal telopeptide of type I collagen (CTX) were
      measured. We analyzed the relationship between serum levels of gonadotropins, E2,
      and bone turnover markers. Serum levels of OC and CTX were positively related to
      FSH (r = 0.234, P = 0.047 and r = 0.384, P = 0.003) and LH (r = 0.319, P = 0.012
      and r = 0.273, P = 0.038). There was no relationship with E2 levels. When
      gonadotropins levels were divided into quartiles, we found significant
      differences in bone turnover markers between the first and the fourth quartile.
      OC levels were higher in the highest quartile of FSH (P = 0.024) and LH (P =
      0.001). Serum CTX was also higher in the highest quartile of FSH (P = 0.004) and
      LH (P = 0.039). FSH levels could explain approximately 14.7% of the chances in
      CTX. In summary, gonadotropins were related to bone turnover in postmenopausal
      healthy women. Moreover, the rise in FSH appears to contribute to higher bone
      resorption. Our results suggest that the measurement of FSH could be usefulness
      to perform a more comprehensive assessment of bone loss in these women.

PMID- 21964647
TI  - Does the risk of stomach cancer remain among second-generation immigrants in
      Sweden?
AB  - The observed increased risks of noncardia stomach cancer among foreign-born
      second-generation immigrants compared to the Swedes suggest that these immigrants
      were infected by Helicobacter pylori before immigration.

PMID- 21964661
TI  - Reliability of the developmental eye movement test.
AB  - PURPOSE: This study evaluated the repeatability of the Developmental Eye Movement
      Test (DEM) with three consecutive administrations on two separate visits to 181
      children between the ages of 6 years and 11 years 11 months. METHODS: Children
      with visual acuity of >= 20/25, normal binocularity, and accommodation were
      administered three different versions of the DEM test. One to 4 weeks after the
      first administration of the DEM, the children were tested again using the same
      order for the three versions of the DEM. Measures of within- and between-session
      repeatability for the vertical-adjusted time, horizontal-adjusted time, ratio,
      and error scores were determined. RESULTS: The within-session repeatability for
      vertical- and horizontal-adjusted time were good to excellent but were poor to
      good for ratio, and poor to fair for errors. The between-session intraclass
      correlation coefficients were fair to good for both the vertical and horizontal
      scores but poor for the ratio and error scores. The repeatability of the pass
      fail diagnostic classification within a single session for each subject on test
      and retest was compared. The percentage of patients who remained in the same
      classification ranged from 71 to 100% for both vertical and horizontal scores.
      Wider variability was seen with the ratio and error scores showing between 47 and
      100% of the children remaining classified as pass or fail with repeated
      administrations of the DEM. Such findings would suggest that children in this age
      range may show improvements in all four test scores without any intervention.
      CONCLUSIONS: Although the DEM is widely used in optometric practice, the results
      of this study suggest that clinicians should be cautious about using the DEM test
      in isolation for reaching a diagnosis or monitoring the effectiveness of
      treatment for saccadic dysfunction.

PMID- 21964662
TI  - Interocular symmetry in myopic anisometropia.
AB  - PURPOSE: To investigate the interocular symmetry of optical, biometric, and
      biomechanical characteristics between the fellow eyes of myopic anisometropes.
      METHODS: Thirty-four young, healthy myopic anisometropic adults (>= 1 D spherical
      equivalent difference between eyes) without amblyopia or strabismus were
      recruited. A range of biometric and optical parameters were measured in both eyes
      of each subject including axial length, ocular aberrations, intraocular pressure,
      corneal topography, and biomechanics. Ocular sighting dominance was also
      measured. RESULTS: Mean absolute spherical equivalent anisometropia was 1.70 +/-
      0.74 D, and there was a strong correlation between the degree of anisometropia
      and the interocular difference in axial length (r = 0.81, p < 0.001). The more
      and less myopic eyes displayed a high degree of interocular symmetry for the
      majority of biometric, biomechanical, and optical parameters measured. When the
      level of anisometropia exceeded 1.75 D, the more myopic eye was more likely to be
      the dominant sighting eye than for lower levels of anisometropia (p = 0.002).
      Subjects with greater levels of anisometropia (>1.75 D) also showed high levels
      of correlation between the dominant and non-dominant eyes in their biometric,
      biomechanical, and optical characteristics. CONCLUSIONS: Although significantly
      different in axial length, anisometropic eyes display a high degree of
      interocular symmetry for a range of anterior eye biometrics and optical
      parameters. For higher levels of anisometropia, the more myopic eye tends to be
      the dominant sighting eye.

PMID- 21964663
TI  - Diffusion models of the flanker task: discrete versus gradual attentional
      selection.
AB  - The present study tested diffusion models of processing in the flanker task, in
      which participants identify a target that is flanked by items that indicate the
      same (congruent) or opposite response (incongruent). Single- and dual-process
      flanker models were implemented in a diffusion-model framework and tested against
      data from experiments that manipulated response bias, speed/accuracy tradeoffs,
      attentional focus, and stimulus configuration. There was strong mimcry among the
      models, and each captured the main trends in the data for the standard
      conditions. However, when more complex conditions were used, a single-process
      spotlight model captured qualitative and quantitative patterns that the dual
      process models could not. Since the single-process model provided the best
      balance of fit quality and parsimony, the results indicate that processing in the
      simple versions of the flanker task is better described by gradual rather than
      discrete narrowing of attention.

PMID- 21964664
TI  - Compound heterozygous deletion of NRXN1 causing severe developmental delay with
      early onset epilepsy in two sisters.
AB  - Neurexin 1 (NRXN1) is a cell adhesion protein, the normal function of which is
      critical for effective neurotransmission. It forms a trans-synaptic complex in
      the central nervous system with neuroligin. There has been one case in the
      literature of a patient with a heterozygous deletion in NRXN1 on one allele and a
      nonsense mutation on the other allele, reported to have a Pitt Hopkins-like
      phenotype. We report on two daughters of healthy, nonconsanguineous, Caucasian
      parents with biallelic NRXN1 deletions identified by array CGH. The children
      presented with severe early onset epilepsy, profound developmental delay,
      gastroesophageal reflux disease, constipation, and early onset puberty. Our
      report confirms that biallelic NRXN1 mutations result in a severe recessive
      mental retardation syndrome and broadens the range of phenotypes associated with
      this gene.

PMID- 21964665
TI  - Botanical species being used for manufacturing plant food supplements (PFS) and
      related products in the EU member states and selected third countries.
AB  - A great wealth of plants and plant derived preparations are used in the intention
      to supplement the basic nutrition in order to sustain and promote health. They
      may be used directly or consumed as manufactured plant food supplements (PFS) in
      dosed form. The use of these plants may already have a long tradition as fruit,
      vegetable or (folk) medicinal plants. Due to globalisation, more and more plants
      originating from all over the world are now offered and marketed in European
      countries, including species from China, South Africa and the American continent.
      For reasons of security, EU wide lists of plants accepted or prohibited to be
      used in food supplements are in elaboration. A crucial point is the correct
      identification of the plant material. The identity can be assessed by
      morphological, chemical and DNA specific methods. The active substances usable in
      PFS are secondary plant products that are often characteristic for certain plant
      groups (taxa), species or plant parts. They comprise not only polyphenols,
      essential oils, carotenoids and phytosterols, but also glucosinolates or
      saponins. The quality of the plant material used for PFS depends on a variety of
      factors, including the natural phytochemical, intraspecific variation with the
      occurrence of chemotypes, the ontogenetic variation, the considered plant parts
      and environmental influences during plant growth. In the production of the raw
      materials for PFS international standards (good agricultural practice, fair
      trade) should be applied.

PMID- 21964666
TI  - Complementary anti-inflammatory effects of a beta-blocker and a corticosteroid in
      an asthma model.
AB  - Glucocorticosteroids are the mainstay treatment for chronic asthma; however,
      adverse effects can limit their usefulness. We previously determined in
      experimental asthma that chronic administration of beta2-adrenoceptor inverse
      agonists reduced airway hyperresponsiveness and indexes of inflammation. However,
      the effect of co-administration of glucocorticosteroids with beta2-adrenoceptor
      inverse agonists is unknown. Therefore, we evaluated the anti-inflammatory effect
      of co-administration of dexamethasone, a glucocorticosteroid, and nadolol, a
      beta2-inverse agonist, in a murine asthma model. We measured eosinophils and
      cytokines in bronchoalveolar lavage fluid and mucin content in epithelial cells
      after exposure to different concentrations of dexamethasone and nadolol.
      Dexamethasone was administered for 3 days and nadolol for 24 days prior to
      ovalbumin challenge. Both drugs were continued during five daily intranasal
      challenges with ovalbumin. Independent administration of dexamethasone (0.4
      mg/kg/day) or nadolol (25 ppm) reduced bronchoalveolar lavage eosinophils by 58%
      and 36%, respectively (P < 0.05). Co-administration of both drugs yielded an
      additive reduction in eosinophils (81%, P < 0.05). Co-administration of both
      drugs (dexamethasone 0.4 mg/kg/day and nadolol 25 ppm) also yielded a greater
      reduction in mucin volume density (83%) than either drug alone (18% for
      dexamethasone and 62% for nadolol) and greater than high-dose dexamethasone (71%)
      alone (P < 0.05). Similarly, co-administration of both drugs (dexamethasone 0.4
      mg/kg/day and nadolol 25 ppm) yielded an additive effect on the reduction of type
      2 cytokines in bronchoalveolar lavage fluid equivalent to the administration of a
      10-fold higher dose of dexamethasone. In Summary, the simultaneous administration
      of a glucocorticosteroid and a beta2-adrenoceptor inverse agonist was more
      effective at reducing indexes of airway inflammation than either drug given
      alone; suggesting nadolol may possess "glucocorticoid-sparing" properties.

PMID- 21964667
TI  - Losartan exerts no protective effects against acute pulmonary embolism-induced
      hemodynamic changes.
AB  - The acute obstruction of pulmonary vessels by venous thrombi is a critical
      condition named acute pulmonary embolism (APE). During massive APE, severe
      pulmonary hypertension may lead to death secondary to right heart failure and
      circulatory shock. APE-induced pulmonary hypertension is aggravated by active
      pulmonary vasoconstriction. While blocking the effects of some vasoconstrictors
      exerts beneficial effects, no previous study has examined whether angiotensin II
      receptor blockers protect against the hemodynamic changes associated with APE. We
      examined the effects exerted by losartan on APE-induced hemodynamic changes.
      Hemodynamic evaluations were performed in non-embolized lambs treated with saline
      (n = 4) and in lambs that were embolized with silicon microspheres and treated
      with losartan (30 mg/kg followed by 1 mg/kg/h, n = 5) or saline (n = 7)
      infusions. The plasma and lung angiotensin-converting enzyme (ACE) activity were
      assessed using a fluorometric method. APE increased mean pulmonary arterial
      pressure (MPAP) and pulmonary vascular resistance index (PVRI) by 21 +/- 2 mmHg
      and 375 +/- 20 dyn s cm-5 m-2, respectively (P < 0.05). Losartan decreased MPAP
      significantly (by approximately 15%), without significant changes in PVRI and
      tended to decrease cardiac index (P > 0.05). Lung and plasma ACE activity were
      similar in both embolized and non-embolized animals. Our findings show evidence
      of lack of activation of the renin-angiotensin system during APE. The lack of
      significant effects of losartan on the pulmonary vascular resistance suggests
      that losartan does not protect against the hemodynamic changes found during APE.

PMID- 21964668
TI  - Reducing the framing effect in older and younger adults by encouraging analytic
      processing.
AB  - OBJECTIVES: The present study explored whether the framing effect could be
      reduced in older and younger adults using techniques that influenced the
      accessibility of information relevant to the decision-making processing.
      Accessibility was manipulated indirectly in Experiment 1 by having participants
      engage in concurrent tasks, and directly in Experiment 2, through an instructions
      manipulation that required participants to maintain a goal of analytic processing
      throughout the experimental trial. METHODS: We tested 120 older and 120 younger
      adults in Experiment 1. Participants completed 28 decision trials while
      concurrently either performing a probability calculation task or a memory task.
      In Experiment 2, we tested 136 older and 136 younger adults. Participants
      completed 48 decision trials after either having been instructed to "think like a
      scientist" or base decisions on "gut reactions." RESULTS: Results demonstrated
      that the framing effect was reduced in older and younger adults in the
      probability calculation task in Experiment 1 and under the "think like a
      scientist" instructions manipulation in Experiment 2. DISCUSSION: These results
      suggest that when information relevant to unbiased decision making was made more
      accessible, both older and younger adults were able to reduce susceptibility to
      the framing effect.

PMID- 21964669
TI  - Confidence intervals for a random-effects meta-analysis based on Bartlett-type
      corrections.
AB  - In medical meta-analysis, the DerSimonian-Laird confidence interval for the
      average treatment effect has been widely adopted in practice. However, it is well
      known that its coverage probability (the probability that the interval actually
      includes the true value) can be substantially below the target level. One
      particular reason is that the validity of the confidence interval depends on the
      assumption that the number of synthesized studies is sufficiently large. In
      typical medical meta-analyses, the number of studies is fewer than 20. In this
      article, we developed three confidence intervals for improving coverage
      properties, based on (i) the Bartlett corrected likelihood ratio statistic, (ii)
      the efficient score statistic, and (iii) the Bartlett-type adjusted efficient
      score statistic. The Bartlett and Bartlett-type corrections improve the large
      sample approximations for the likelihood ratio and efficient score statistics.
      Through numerical evaluations by simulations, these confidence intervals
      demonstrated better coverage properties than the existing methods. In particular,
      with a moderate number of synthesized studies, the Bartlett and Bartlett-type
      corrected confidence intervals performed well. An application to a meta-analysis
      of the treatment for myocardial infarction with intravenous magnesium is
      presented.

PMID- 21964670
TI  - Interventional spinal procedures guided and controlled by a 3D rotational
      angiographic unit.
AB  - OBJECTIVE: The aim of this paper is to demonstrate the usefulness of 2D
      multiplanar reformatting images (MPR) obtained from rotational acquisitions with
      cone-beam computed tomography technology during percutaneous extra-vascular
      spinal procedures performed in the angiography suite. METHODS: We used a 3D
      rotational angiographic unit with a flat panel detector. MPR images were obtained
      from a rotational acquisition of 8 s (240 images at 30 fps), tube rotation of 180
      degrees  and after post-processing of 5 s by a local work-station. Multislice CT
      (MSCT) is the best guidance system for spinal approaches permitting direct
      tomographic visualization of each spinal structure. Many operators, however, are
      trained with fluoroscopy, it is less expensive, allows real-time guidance, and in
      many centers the angiography suite is more frequently available for percutaneous
      procedures. We present our 6-year experience in fluoroscopy-guided spinal
      procedures, which were performed under different conditions using MPR images. We
      illustrate cases of vertebroplasty, epidural injections, selective foraminal
      nerve root block, facet block, percutaneous treatment of disc herniation and
      spine biopsy, all performed with the help of MPR images for guidance and control
      in the event of difficult or anatomically complex access. RESULTS AND CONCLUSION:
      The integrated use of "CT-like" MPR images allows the execution of spinal
      procedures under fluoroscopy guidance alone in all cases of dorso-lumbar access,
      with evident limitation of risks and complications, and without need for recourse
      to MSCT guidance, thus eliminating CT-room time (often bearing high diagnostic
      charges), and avoiding organizational problems for procedures that need, for
      example, combined use of a C-arm in the CT room.

PMID- 21964671
TI  - CT-guided cervical nerve root injections: comparing the immediate post-injection
      anesthetic-related effects of the transforaminal injection with a new indirect
      technique.
AB  - OBJECTIVE: To describe an "indirect" cervical nerve root injection technique with
      a dorsal approach that should carry less inherent risk than the "direct" cervical
      transforaminal injection approach, and to compare the immediate post-injection
      results of the two procedures. MATERIALS AND METHODS: The indirect and direct
      cervical nerve root injection procedures are described in detail. Fifty-three
      consecutive patients receiving the indirect nerve root injections during 2009
      2010 were age- and gender-matched to 53 patients who underwent direct
      transforaminal nerve root injections performed in 2006. Pain level data were
      collected immediately before and 20-30 min after each procedure. The percentages
      of pain change in the two groups were compared using the unpaired Student's t
      test. RESULTS: Fifty-two men (mean age 49) and 54 women (mean age 55) were
      included. The mean percentage of pain reduction for patients receiving indirect
      nerve root injections was 38.4% and for those undergoing the direct nerve root
      injections approach it was 43.2%. This was not significantly different (P =
      0.455). No immediate or late adverse effects were reported after either injection
      procedure. CONCLUSIONS: The indirect cervical nerve root injection procedure is a
      potentially safer alternative to direct cervical transforaminal nerve root
      injections. The short-term pain reduction is similar using the two injection
      methods.

PMID- 21964673
TI  - Residential characteristics and radiofrequency electromagnetic field exposures
      from bedroom measurements in Germany.
AB  - The objectives of this study were to assess total exposure to radiofrequency
      electromagnetic fields (RF-EMF) in bedrooms and the contribution of different
      radioservices (FM radio, analogue TV and DVB-T, TETRA, GSM900 downlink, GSM1800
      downlink, UMTS downlink, DECT, and wireless LAN and blue tooth) to the total
      exposure. Additional aims were to describe the proportion of measuring values
      above the detection limit of the dosimeters and to characterize the differences
      in exposure patterns associated with self-reported residential characteristics.
      Exposure to RF sources in bedrooms was measured using Antennessa((r)) EME Spy 120
      dosimeters in 1,348 households in Germany; 280 measures were available for each
      frequency band per household. Mean electrical field strengths and power flux
      densities were calculated. Power flux densities allow the calculation of
      proportions of different radioservices on total exposure. Exposure was often
      below the detection limit (electrical field strength: 0.05 V/m) of the dosimeter.
      Total exposure varied, depending on residential characteristics (urban vs. rural
      areas and floor of a building the measurement took place). Major sources of
      exposure were cordless phones (DECT standard) and wireless LAN/blue tooth
      contributing about 82% of total exposure (20.5 MUW/m(2)). Exposure to RF-EMF is
      ubiquitous, but exposure levels are-if at all measurable-very low and far below
      the ICNIRP's exposure reference levels.

PMID- 21964672
TI  - Posttraining flavor exposure in hungry rats after simultaneous conditioning with
      a nutrient converts the CS into a conditioned inhibitor.
AB  - The present study investigated the decrement in nutrient-based conditioned flavor
      preference found in hungry rats exposed to a flavor following simultaneous flavor
      sucrose conditioning while thirsty. Although a significant decrease in preference
      was found in the experimental group in each experiment, there was no evidence of
      either spontaneous recovery (Experiment 1) or reinstatement (Experiment 2). In
      addition, posttraining flavor exposure weakened the original flavor-sucrose
      association (Experiment 3). These results suggested that the flavor-US
      association might have been impaired after posttraining flavor exposure. Two
      further experiments assessed whether the flavor acquired the properties of a net
      inhibitor, using the retardation and summation tests for conditioned inhibition.
      Experiment 4 revealed that the flavor suffered retardation when retraining was
      conducted after the exposure phase. In Experiment 5, the target flavor decreased
      the preference shown for a different flavor previously paired simultaneously with
      sucrose when both were presented forming an unreinforced compound in the
      summation tests. None of these effects was found in a control group, which had
      received serial flavor -> nutrient presentations during training. Together, these
      results suggest that a flavor simultaneously paired with sucrose acquires the
      properties of a net inhibitor when it is subsequently presented outside the
      compound to hungry animals.

PMID- 21964674
TI  - Combined modality therapy for laryngeal cancer with superselective intra-arterial
      cisplatin infusion and concomitant radiotherapy.
AB  - Concomitant radiotherapy and superselective arterial infusion of cisplatin for
      laryngeal cancer has shown excellent therapeutic outcomes. It is expected to be a
      reasonable treatment option for laryngeal cancer, especially in locally advanced
      cases.

PMID- 21964675
TI  - Paget's disease of the vulva: a clinicopathologic institutional review.
AB  - BACKGROUND: The aim of this study was to assess the clinicopathologic
      characteristics of patients with Paget's disease of the vulva who were treated by
      our gynecologic oncology service between 1985 and 2010. METHODS: Vulvar Paget's
      disease patient demographics, pathologic diagnosis, treatment and follow-up data
      were reviewed over a 25-year period. RESULTS: The vulvar Paget's disease patients
      were primarily (62.5%) treated with a partial simple vulvectomy. Three patients
      had a history of malignancy, although none of them was intercurrent. Eleven
      patients had microscopically positive margins, 5 of whom developed progressive
      disease. Conversely, 5 patients had negative margins, of whom 4 had recurrent
      disease. There was a significant relationship between the presence of invasive
      disease and patient progression-free interval (PFI) (p = 0.007), but margin
      status and lesion size did not correlate with PFI (p > 0.05). Median patient PFI
      and follow-up was 30 and 53 months, respectively. CONCLUSIONS: We found a
      significant relationship between the presence of invasive disease and patient PFI
      in vulvar Paget's disease although the presence of microscopic positive margins
      and lesion size were not prognostic indicators. In patients with high risk
      factors, prolonged surveillance should be considered an essential component of
      optimal patient management.

PMID- 21964676
TI  - Hepatocyte induced re-expression of E-cadherin in breast and prostate cancer
      cells increases chemoresistance.
AB  - Post-extravasation survival is a key rate-limiting step of metastasis; however,
      not much is known about the factors that enable survival of the metastatic cancer
      cell at the secondary site. Furthermore, metastatic nodules are often refractory
      to current therapies, necessitating the elucidation of molecular changes that
      affect the chemosensitivity of metastases. Drug resistance exhibited by tumor
      spheroids has been shown to be mediated by cell adhesion and can be abrogated by
      addition of E-cadherin blocking antibody. We have previously shown that
      hepatocyte coculture induces the re-expression of E-cadherin in breast and
      prostate cancer cells. In this study, we show that this E-cadherin re-expression
      confers a survival advantage, particularly in the liver microenvironment. E
      cadherin re-expression in MDA-MB-231 breast cancer cells resulted in increased
      attachment to hepatocytes. This heterotypic adhesion between cancer cells and
      secondary organ parenchymal cells activated ERK MAP kinase, suggesting a
      functional pro-survival role for E-cadherin during metastatic colonization of the
      liver. In addition, breast cancer cells that re-expressed E-cadherin in
      hepatocyte coculture were more chemoresistant compared to 231-shEcad cells unable
      to re-express E-cadherin. Similar results were obtained in DU-145 prostate cancer
      cells induced to re-express E-cadherin in hepatocyte coculture or following
      chemical induction by the GnRH agonist buserelin or the EGFR inhibitor PD153035.
      These results suggest that E-cadherin re-expression and other molecular changes
      imparted by a partial mesenchymal to epithelial reverting transition at the
      secondary site increase post-extravasation survival of the metastatic cancer cell
      and may help to elucidate why chemotherapy commonly fails to treat metastatic
      breast cancer.

PMID- 21964677
TI  - Magnetic resonance imaging measurement reproducibility for calf muscle and
      adipose tissue volume.
AB  - PURPOSE: To describe a new semiautomated method for segmenting and measuring the
      volume of the muscle, bone, and adipose (subcutaneous and intermuscular) tissue
      in calf muscle compartments using magnetic resonance (MR) images and determine
      the intrarater and interrater reproducibility of the measures. MATERIALS AND
      METHODS: Proton-density weighted MR images were acquired from the right calf of
      21 subjects. Three raters segmented and measured the volumes of bones, adipose
      tissue, and five individual muscle compartments. Two raters repeated the
      segmentations. The intra- and interrater reproducibility of the measures
      (intraclass correlation coefficients; ICC) were determined using generalizability
      theory. RESULTS: All ICC values were greater than 0.96. The average standard
      error of the mean (SEM) of all measures was 1.21 cm(3) and none were greater than
      2.3 cm(3) . Essentially all variation (>=97% for all measures) was due to subject
      differences, indicating low error in the measurements. CONCLUSION: The volumetric
      measurements for the bones, adipose tissue, and muscle in each of the
      compartments using MRI were highly reproducible. MRI can provide quantitative,
      reproducible volumetric measures of bone, adipose tissue, and individual muscle
      compartments in the calf. We believe these methods can be used to quantify
      specific muscle or adipose volumetric measures for other clinical or research
      purposes.

PMID- 21964678
TI  - Breast implants: the good, the bad and the ugly. Can nanotechnology improve
      implants?
AB  - This advanced review will discuss the history of implants used in breast
      reconstruction and augmentation, the most frequently performed plastic surgery
      today. Currently, only silicone rubber-based silica nanocomposite implants are
      available in the United States. The most prevalent issues involving breast
      implants include capsular contracture, gel bleed, implant rupture, and infection.
      In the past, studies have also been reported which linked breast implants to
      increased incidence of systemic diseases such as autoimmune disease, various
      forms of cancer, and psychological disease. The goal of this review is to survey
      the literature from the perspective of material science. It is also largely
      unnoticed that nanotechnology is involved: the silicone rubber shell is
      reinforced with nanosilica so implants appear to be homogeneous and crystal
      clear. We are hoping that this review will contribute to a better understanding
      of the controversial issues and motivate material scientists and medical doctors
      to work together to develop alternatives based on new nanotechnology for the
      women who opt for a device made of synthetic materials.

PMID- 21964680
TI  - Systematic review of perianal implants in the treatment of faecal incontinence.
AB  - BACKGROUND: Injectable bulking agents have been used with varying success for the
      treatment of faecal incontinence. This systematic review aimed to investigate the
      various injectable agents and techniques used for the treatment of faecal
      incontinence, and to assess their safety and efficacy. METHODS: Thirty-nine
      publications were identified and studied. The following variables were pooled for
      univariable analysis: type, location, route of bulking agents, and the use of
      ultrasound guidance, antibiotics, laxatives and anaesthetics. Predictors of the
      development of complications and successful outcomes were identified by
      multivariable logistic regression analysis. RESULTS: A total of 1070 patients
      were included in the analysis. On multivariable analysis, the only significant
      predictor of the development of complications was the route of injection of
      bulking agents (odds ratio 3.40, 95 per cent confidence interval 1.62 to 7.12; P
      = 0.001). Two variables were significant predictors of a successful short-term
      outcome: the use of either PTQ((r)) (OR 5.93, 2.21 to 16.12; P = 0.001) or
      Coaptite((r)) (OR 10.74, 1.73 to 65.31; P = 0.001) was associated with a greater
      likelihood of success. Conversely, the use of local anaesthetic was associated
      with a lower likelihood of success (OR 0.18, 0.05 to 0.59; P = 0.005). Failure to
      use laxatives in the postoperative period resulted in a poorer medium- to longer
      term outcome (OR 0.13, 0.06 to 0.25; P = 0.001). CONCLUSION: This systematic
      review has identified variations in the practice of injection of bulking agents
      that appear to influence the likelihood of complications and affect the outcomes
      after treatment.

PMID- 21964679
TI  - Management of postoperative nausea and vomiting in women scheduled for breast
      cancer surgery.
AB  - Breast cancer surgery performed under general anesthesia is associated with a
      high incidence of postoperative nausea and vomiting (PONV). A number of
      approaches are available for the management of PONV after breast cancer surgery.
      First, the risk factors related to patient characteristics, surgical procedure,
      anesthetic technique, and postoperative care can be reduced. More specifically,
      the use of propofol-based anesthesia can reduce the incidence of PONV. Secondly,
      a wide range of prophylactic antiemetics, including butyrophenones (droperidol),
      benzamides (metoclopramide), glucocorticoids (dexamethasone), clonidine, a small
      dose of propofol, and serotonin receptor (SR) antagonists (ondansetron,
      granisetron, tropisetron, dolasetron, ramosetron, and palonosetron), are
      available for preventing PONV. Thirdly, antiemetic therapy combined with
      granisetron and droperidol or dexamethasone, and a multimodal management strategy
      which includes a package consisting of dexamethasone, total intravenous
      anesthesia with propofol, and ondansetron are highly effective in preventing
      PONV. Unfortunately, the use of glucocorticoids and SR antagonists for preventing
      PONV is not permitted in Japan according to national health insurance guidelines.
      Fourth, electro-acupoint stimulation at the P6 point (Nei-Guwan) as a non
      pharmacologic therapy is as effective as ondansetron for preventing PONV.
      Knowledge of the risk factors for PONV, antiemetics, and a non-pharmacologic
      approach are needed for the management of PONV in women undergoing breast cancer
      surgery.

PMID- 21964681
TI  - Randomized clinical trial of fibrin sealant versus titanium tacks for mesh
      fixation in laparoscopic umbilical hernia repair.
AB  - BACKGROUND: The use of tacks for mesh fixation may induce pain after surgery for
      ventral hernia. The aim of this study was to compare postoperative pain after
      laparoscopic ventral hernia repair (LVHR) with conventional mesh fixation using
      titanium tacks versus fibrin sealant (FS). METHODS: This randomized clinical
      trial included patients with an umbilical hernia defect ranging from 1.5 to 5 cm
      at three Danish hernia centres. Participants were assigned randomly to FS or
      titanium tack fixation. The primary outcome was acute pain, defined as the mean
      pain score on days 0-2 after surgery, measured on a 0-100-mm visual analogue
      scale (VAS). RESULTS: Forty patients were included, of whom 38 were available for
      intention-to-treat analysis after 1 month. Patients in the FS group reported less
      pain than those in the tack group on days 0-2, both at rest (median 19 versus 47
      mm; P = 0.025) and during activity (38 versus 60 mm; P = 0.014). The absolute
      difference in pain score between groups was 19 (95 per cent confidence interval 3
      to 34) and 20 (4 to 35) mm at rest and during activity respectively. Patients in
      the FS group resumed normal daily activity earlier (after median 7 versus 18
      days; P = 0.027) and reported significantly less discomfort. No recurrences were
      observed. CONCLUSION: Mesh fixation with FS in LVHR was associated with less
      acute postoperative pain, discomfort and a shorter convalescence than tack
      fixation. Long-term follow-up is needed to show whether the effect of FS fixation
      persists in terms of chronic pain and recurrence. REGISTRATION NUMBER:
      NCT00842842 (http://www.clinicaltrials.gov).

PMID- 21964682
TI  - Randomized clinical trial of fibrin sealant versus titanium tacks for mesh
      fixation in laparoscopic umbilical hernia repair (Br J Surg 2011; 98: 1537-1545).

PMID- 21964683
TI  - Long-term results after laparoscopic reoperation for failed antireflux procedures
      (Br J Surg 2011; 98: 1581-1587).

PMID- 21964684
TI  - Management and outcomes of haemorrhage after pancreatogastrostomy versus
      pancreatojejunostomy.
AB  - BACKGROUND: Postpancreatectomy haemorrhage (PPH) is a major cause of morbidity
      and mortality after pancreaticoduodenectomy (PD). It remains unclear whether
      performance of a pancreatogastrostomy (PG) instead of a pancreatojejunostomy (PJ)
      improves outcomes owing to better endoscopic accessibility. METHODS: A large
      retrospective analysis was undertaken to compare outcomes of PPH, depending on
      whether a PG or PJ was performed. The primary outcome was the rate of successful
      endoscopy. A secondary outcome was the therapeutic success after adding surgery.
      RESULTS: Of 944 patients who had a PD, 8.4 per cent developed PPH. Endoscopy was
      the primary intervention in 21 (81 per cent) of 26 patients with a PG and 34 (64
      per cent) of 53 with a PJ; it identified the bleeding site in 35 and 25 per cent
      respectively (P = 0.347). Successful endoscopic treatment was more common in the
      PG group (31 versus 9 per cent; P = 0.026). Surgery was performed for PPH in 15
      patients (58 per cent) with a PG and 35 (66 per cent) with a PJ (P = 0.470). The
      majority of haemorrhages that required surgery were non-anastomotic intra
      abdominal haemorrhages (12 of 15 versus 21 of 35; P = 0.171). Endoscopic or
      conservative treatment for PPH was successful in 42 per cent of patients with a
      PG and 32 per cent with a PJ (P = 0.520). The success rate increased to 85 and 91
      per cent respectively when surgery was included in the algorithm (P = 0.467).
      CONCLUSION: The type of pancreatic anastomosis and its inherent effect on
      endoscopic accessibility had very little impact on the outcome of PPH. This was
      because haemorrhage frequently occurred from intra-abdominal or non-anastomotic
      intraluminal lesions.

PMID- 21964685
TI  - Management and outcomes of haemorrhage after pancreatogastrostomy versus
      pancreatojejunostomy (Br J Surg 2011: 98: 1599-1607).

PMID- 21964686
TI  - Long-term functional results and quality of life after transanal endoscopic
      microsurgery (Br J Surg 2011; 98: 1635-1643).

PMID- 21964687
TI  - Novel bulking agent for faecal incontinence (Br J Surg 2011; 98: 1644-1652).

PMID- 21964688
TI  - Randomized clinical trial of epidural, spinal or patient-controlled analgesia for
      patients undergoing laparoscopic colorectal surgery (Br J Surg 2011; 98: 1068
      1078).

PMID- 21964690
TI  - Role of mammography in the triple assessment of single-quadrant breast symptoms
      (Br J Surg 2011; 98: 951-955).

PMID- 21964691
TI  - Systematic review of outcome of downstaging hepatocellular cancer before liver
      transplantation in patients outside the Milan criteria (Br J Surg 2011; 98: 1201
      1208).

PMID- 21964697
TI  - Pediatric high grade glioma of the spinal cord: results of the HIT-GBM database.
AB  - Little is known about pediatric spinal cord high grade gliomas (SCHGG) beyond
      their dismal prognosis. Here, we analyzed the HIT-GBM((r)) database for the
      influence of surgical resection on survival. Between 1991 and 2010 the HIT-GBM
      group collected data from European children diagnosed with high grade glioma.
      Patients with the following inclusion criteria were analyzed in this study:
      astrocytic histology, WHO grade III or IV, age at diagnosis <18 years, and tumor
      localized to the spinal cord. 28 patients (mean age 11.28 years, 14 male) with
      primary SCHGG were identified. The tumor sizes were measured by the span across
      adjacent vertebrae and varied greatly (range: 1-20, median: 4). Histology was
      classified as WHO grade III in 15 and grade IV in 13 tumors. Of note, the four
      largest tumors identified were WHO grade III. Surgery was classified as complete
      resection (n = 6), subtotal resection (STR) (n = 7), partial resection (n = 12)
      or biopsy only (n = 3). 27 patients received chemotherapy, 22 of which also
      received radiation. With the mean follow-up time of 2.88 (SD +/- 2.95) years, 14
      patients were still alive resulting in a median overall survival of 2.5 years (SE
      +/- 1.6). The positive prognostic indicators for overall survival were: age
      younger than 5 years (P = 0.047), WHO grade III (P = 0.046), absence of necrosis
      (P = 0.025) and gross total resection (GTR) (P = 0.012). The prognosis of SCHGG
      might not be as miserable as generally assumed. GTR is of benefit. Larger data
      sets and meta-analysis are necessary to identify patient sub-groups.

PMID- 21964696
TI  - The feasibility of real-time in vivo optical detection of blood-brain barrier
      disruption with indocyanine green.
AB  - Osmotic disruption of the blood-brain barrier (BBB) by intraarterial mannitol
      injection is sometimes required for the delivery of chemotherapeutic drugs to
      brain tissue. Osmotic disruption is affected by a number of factors, and there is
      a significant variability in the degree and distribution of BBB disruption in
      clinical and experimental settings. Brain tissue concentrations of indocyanine
      green (ICG) can be measured by optical techniques. The aim of this experiment was
      to determine whether the disruption of the BBB significantly altered the regional
      pharmacokinetics of ICG. We were able to track in vivo brain tissue
      concentrations of ICG in 13 New Zealand white rabbits by employing a novel
      optical approach. Evan's blue was used to assess the distribution of BBB
      disruption on post mortem examination. BBB disruption by intraarterial mannitol
      injection was found to be highly variable, and only five of the 13 animals
      demonstrated the disruption at the site of optical measurements. In these
      animals, we observed a ninefold increase in ICG concentrations and fourfold
      increase in the area under the concentration-time curve, compared to those
      without BBB disruption at the site of measurement. This study shows the
      feasibility of optical monitoring of BBB disruption with intravenous (IV) ICG
      injections. Virtual real-time optical monitoring of the BBB disruption could help
      improve intraarterial delivery of chemotherapeutic drugs.

PMID- 21964698
TI  - A simple protocol for amino acid type selective isotope labeling in insect cells
      with improved yields and high reproducibility.
AB  - An easy to use and robust approach for amino acid type selective isotope labeling
      in insect cells is presented. It relies on inexpensive commercial media and can
      be implemented in laboratories without sophisticated infrastructure. In contrast
      to previous protocols, where either high protein amounts or high incorporation
      ratios were obtained, here we achieve both at the same time. By supplementing
      media with a well considered amount of yeast extract, similar protein amounts as
      with full media are obtained, without compromising on isotope incorporation. In
      single and dual amino acid labeling experiments incorporation ratios are
      consistently >=90% for all amino acids tested. This enables NMR studies of
      eukaryotic proteins and their interactions even for proteins with low expression
      levels. We show applications with human kinases, where protein-ligand
      interactions are characterized by 2D [(15)N, (1)H]- and [(13)C, (1)H]-HSQC
      spectra.

PMID- 21964699
TI  - Influence of common preanalytical variations on the metabolic profile of serum
      samples in biobanks.
AB  - A blood pre-centrifugation delay of 24 h at room temperature influenced the
      proton NMR spectroscopic profiles of human serum. A blood pre-centrifugation
      delay of 24 h at 4 degrees C did not influence the spectroscopic profile as
      compared with 4 h delays at either room temperature or 4 degrees C. Five or ten
      serum freeze-thaw cycles also influenced the proton NMR spectroscopic profiles.
      Certain common in vitro preanalytical variations occurring in biobanks may impact
      the metabolic profile of human serum.

PMID- 21964700
TI  - Anti-proliferative effects of cucurmosin on human hepatoma HepG2 cells.
AB  - We extracted cucurmosin (CUS) from the sarcocarp of Cucrubita moschata (pumpkin).
      Recently, a number of studies have indicated that CUS has cytotoxic properties
      and induces apoptosis in a number of human tumor cells. However, the detailed
      mechanisms are largely unknown. The aim of this study was to confirm CUS's
      anticancer activity on human hepatoma HepG2 cells in vitro and in vivo, and to
      elucidate the mechanism of its activity. MTT was used to detect the cytotoxic
      effects of CUS. Flow cytometry was used to analyze cell apoptosis and the cell
      cycle. Transmission electron microscopy was used to observe the morphology of
      apoptotic cells. Western blot analysis was performed to measure the protein
      expression of bax, bcl-2 and procaspase-3. The established orthotopic
      transplantation models of human hepatoma in NOD/SCID mice were tested for
      anticancer activities in vivo. The results showed that CUS inhibited the
      proliferation of HepG2 cells in vitro and in vivo. CUS induced apoptosis and
      arrested the cell cycle. In addition, CUS increased the protein expression of
      bax, but decreased the bcl-2 and procaspase-3 expression in HepG2 cells. Our data
      indicate that CUS has potential anticancer activity for human hepatoma, which can
      be attributed in part to its inhibition of proliferation and apoptosis, induced
      by decreasing the bcl-2:bax ratio and caspase-3 activation.

PMID- 21964701
TI  - Progressive leukoencephalopathy with intracranial calcification, congenital
      deafness, and developmental deterioration.
AB  - We report on a 12-year-old male with a unique cerebral white matter disease. His
      initial symptoms were congenital hearing loss and multiple intracranial
      calcifications on head CT. He developed severe intellectual disability and
      epilepsy. MRI showed signal abnormalities in the posterior limbs of the internal
      capsules, thalami, and cerebral white matter. The abnormalities were progressive
      over time. The neuropathology revealed diffuse and severe disruption of myelin
      and axons of the cerebral white matter and cerebrospinal tracts. We performed
      various metabolic examinations, detailed pathological investigations and genetic
      analyses, but could not identify the cause. To our knowledge his clinical course
      has not been described in the literature.

PMID- 21964702
TI  - Modulation of attention in discrimination learning: the roles of stimulus
      relevance and stimulus-outcome correlation.
AB  - The advantage in learning after an intradimensional shift rather than an
      extradimensional shift has been widely used as a behavioural marker of
      attentional changes during discrimination learning in different fields of
      neuroscientific study. However, some of the factors assumed to guide these
      attentional changes have not been completely disentangled by previous research.
      In two predictive-learning experiments, we investigated the importance of
      stimulus relevance and of stimulus-outcome correlation for the modulation of
      attention. In each experiment, participants were trained on two discrimination
      problems given in successive order. Each problem required participants to
      differentiate stimuli varying on two dimensions. We found that acquisition of the
      second discrimination was influenced by whether its relevant dimension (Exp. 1)
      or its irrelevant dimension (Exp. 2) had previously been trained as relevant and
      uncorrelated or as irrelevant and uncorrelated. We also observed that acquisition
      of the second discrimination was independent of whether its relevant dimension
      (Exp. 1) or its irrelevant dimension (Exp. 2) had previously been trained as
      relevant and uncorrelated or as relevant and correlated. Our results indicated
      that the modulation of attention is guided by stimulus relevance and not by
      stimulus-outcome correlation.

PMID- 21964703
TI  - Two different dosing regimens of human recombinant erythropoietin beta during
      preoperative autologous blood donation in patients having hip arthroplasty.
AB  - PURPOSE: Our aim was to evaluate the effectiveness of two different dosing
      regimens of human recombinant erythropoietin (rHu-EPO) for preoperative
      autologous blood collection in patients undergoing total hip arthroplasty (THA).
      METHODS: Prospective randomised trials in which erythropoietin 15,000 IU was
      administered intravenously twice a week or 30,000 IU once a week (total 90,000
      IU) combined with ferrous II sulphate (Ferro-Gradumet 2) orally and compared with
      Ferro-Gradumet 2 alone. RESULTS: Although different dosing regimens of rHu-EPO
      administration during preoperative autologous blood donation have similar effects
      on the collection of two units of autologous blood, preoperative haemoglobin
      level and perioperative allogenic blood transfusion, a once weekly dose regimen
      of rHu-EPO was more convenient (although not statistically significantly) for
      patients. CONCLUSION: We recommend the more practical and comfortable but yet
      highly effective therapeutic regimen with a single weekly intravenous
      administration of rHu-EPO for patients scheduled for THA.

PMID- 21964705
TI  - Laparoscopic hepato-biliary-pancreatic surgery: present practices and prospects.

PMID- 21964704
TI  - Sunitinib-induced nephrotic syndrome and irreversible renal dysfunction.
AB  - Sunitinib, a tyrosine kinase inhibitor targeting vascular endothelial growth
      factor receptors (VEGFRs), has become essential for treating imatinib-resistant
      malignant gastrointestinal stromal tumor. Recently, several cases have been
      reported that showed proteinuria and kidney dysfunction to be associated with
      anti-VEGF therapy. Although previous reports indicated that this side-effect is
      reversible, it is not well understood. We present here the case of a 72-year-old
      man who presented with nephrotic syndrome and renal dysfunction 6 months after
      administration of sunitinib. Sunitinib was discontinued, and nephrotic syndrome
      remitted spontaneously, but renal function recovery was limited. Nine months
      later, a renal biopsy was performed because sunitinib was again required and
      pathological examination was needed. The renal biopsy showed marked endothelial
      cell injury with focal segmental glomerulosclerosis and accelerated VEGF
      expression by podocytes. Sunitinib was then given at a reduced dose. Kidney
      dysfunction and nephrotic syndrome are rare but serious complications of
      sunitinib. The present case suggests that long-term treatment with a high dose of
      sunitinib can cause irreversible renal dysfunction, and that low-dose treatment
      makes these side-effects manageable.

PMID- 21964706
TI  - Mechanism of arterial remodeling in chronic allograft vasculopathy.
AB  - Chronic allograft vasculopathy (CAV) remains a major obstacle for long-term
      survival of grafts even though therapeutic strategies have improved considerably
      in recent years. CAV is characterized by concentric and diffuse neointimal
      formation, medial apoptosis, infiltration of lymphocyte or inflammatory cells,
      and deposition of extracellular matrix both in arteries and veins. Recent studies
      have shown that stem cells derived from the recipient contribute to neointimal
      formation under the regulation of chemokines and cytokines. Arterial remodeling
      in allografts eventually causes ischemic graft failure. The pathogenesis is multi
      factorial with both immunologic and non-immunological factors being involved. The
      immunological factors have been discussed extensively in other articles. This
      review focuses mainly on the arterial remodeling that occurs in 3 layers of
      vessel walls including intimal injury, accumulation of smooth muscle-like cells
      in the neointimal, medial smooth muscle cell apoptosis, adventitial fibrosis, and
      deposition of extracellular matrix.

PMID- 21964708
TI  - Towards the optimization of management of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common neoplasm in the world,
      closely correlated with viral hepatitis and liver cirrhosis. The vast majority of
      HCC patients present at a late stage and are unsuitable for surgery due to
      limited liver functional reserve. Tumors can involve major vessels or hilar
      structures, necessitating major liver resection and/or rendering liver resection
      unfeasible. A series of new technologies have been developed to optimise HCC
      management. Stem cell therapy improves impaired liver functional reserve prior to
      liver resection. Intravascular radiofrequency ablation recanalises the portal
      vein invaded by tumour thrombus and endobiliary radiofrequency ablation restores
      and extends biliary patency of the bile duct invaded by malignancy. Laparoscopic
      radiofrequency assisted liver resection minimizes blood loss and avoids liver
      warm ischemia, while increasing parenchymal sparing. These benefits combined
      maximize the safety of liver resection.

PMID- 21964707
TI  - Multislice computed tomography angiography in the diagnosis of cardiovascular
      disease: 3D visualizations.
AB  - Multislice computed tomography (CT) has been widely used in clinical practice for
      the diagnosis of cardiovascular disease due to its reduced invasiveness and high
      spatial and temporal resolution. As a reliable alternative to conventional
      angiography, multislice CT angiography has been recognized as the method of
      choice for detecting and diagnosing head and neck vascular disease, abdominal
      aortic aneurysm, aortic dissection, and pulmonary embolism. In patients with
      suspected coronary artery disease, although invasive coronary angiography still
      remains as the gold standard technique, multislice CT angiography demonstrates
      high diagnostic accuracy; in selected patients, it is considered as the first
      line technique. The imaging diagnosis of cardiovascular disease is based on a
      combination of two-dimensional (2D) and three-dimensional (3D) visualization
      tools to enhance the diagnostic value. This is facilitated by reconstructed
      visualizations which provide additional information about the extent of the
      disease, an accurate assessment of the spatial relationship between normal
      structures and pathological changes, and pre-operative planning and post
      procedure follow-up. The aim of the present article is to present an overview of
      the diagnostic performance of various 2D and 3D CT visualizations in
      cardiovascular disease, including multiplanar reformation, maximum intensity
      projection, volume rendering, and virtual intravascular endoscopy. The
      recognition of the potential value of these visualizations will assist clinicians
      in efficiently using the multislice CT imaging modality for the diagnostic
      management of patients with cardiovascular disease.

PMID- 21964709
TI  - Laparoscopic surgery for pancreatic lesions: current status and future.
AB  - Laparoscopic pancreatic surgery has been gaining increasing recognition in recent
      years, and its practice has increased despite its highly complex procedure and
      longer learning curve compared with surgeries for other abdominal organs.
      Laparoscopic distal pancreatectomy and tumor enucleation are two of the fastest
      growing techniques and are currently in wide use because of their comparable
      technical simplicity. Literature review showed that laparoscopic distal
      pancreatectomy and enucleation are safe and efficient approaches for benign and
      low-degree malignant tumors; however, the indication for malignant tumors remains
      controversial. Laparoscopic pancreaticoduodenectomy is practiced in a limited
      number of surgical centers and presented as case reports or in small series.
      Although its feasibility was demonstrated by many surgeons, whether the
      laparoscopic procedure can achieve benefits comparable to or even more prominent
      than those of an open procedure has not been clinically proven. Prospective,
      randomized, controlled trials of laparoscopic operation versus open pancreatic
      surgery are necessary to justify the wide application and routine practice of the
      laparoscopic procedure for pancreatic lesions.

PMID- 21964710
TI  - Single incision laparoscopic cholecystectomy using the one-incision three-trocar
      technique with all straight instruments: how I do it?
AB  - Single incision laparoscopic surgery (SILS) is a novel minimally invasive
      surgical technique that is gaining popularity around the world. One of the most
      commonly performed procedures is single incision laparoscopic cholecystectomy
      (SILC). Most reported techniques utilize special purpose-made access port and
      articulating instruments, rendering the procedure costly and difficult to learn.
      This article provides a stepwise description of SILC technique using all straight
      instruments without the need for a special port. It aims to shorten the learning
      curve for surgeons wishing to adopt a safe and cost-effective SILC technique to
      their practice.

PMID- 21964711
TI  - Type 2 diabetic patients with non-alcoholic fatty liver disease exhibit
      significant haemorheological abnormalities.
AB  - Haemorheological abnormalities have been described in diabetes mellitus, as well
      as in non-alcoholic fatty liver disease (NAFLD). However, the relationship
      between the changes in liver fat content and haemorheology is unknown. The
      current study aims to show the correlation between haemorheological parameters
      and intrahepatic lipid content (IHLC) in patients with type 2 diabetes. The serum
      biochemical markers, such as fasting plasma glucose (FPG), haemoglobin A1c
      (HbA1c), liver enzymes, lipid profiles, and haemorheological properties, were
      examined. IHLC was quantified using proton magnetic resonance spectroscopy ((1)H
      MRS) scanning of the liver. A significant correlation was observed between IHLC
      and whole blood viscosity at high, middle, and low shear rates. IHLC also
      positively correlated with haematocrit, the reduced whole blood viscosity at low
      and middle shear rates, and the erythrocyte aggregation index. Diabetic patients
      with NAFLD exhibited significant haemorheological abnormalities compared with
      patients without NAFLD. In summary, haemorheological disorders are linked to non
      alcoholic fatty liver in type 2 diabetes.

PMID- 21964712
TI  - c-Fos expression in rat brainstem following intake of sucrose or saccharin.
AB  - To examine whether the activation of brainstem neurons during intake of a sweet
      tastant is due to orosensory signals or post-ingestive factors, we compared the
      distribution of c-Fos-like immunoreactivity (c-FLI) in the nucleus of the
      solitary tract (NST) and parabrachial nucleus (PBN) of brainstem following
      ingestion of 0.25 Msucrose or 0.005 M saccharin solutions. Immunopositive neurons
      were localized mainly in the middle zone of the PBN and four rostral-caudal
      subregions of the NST. Intake of sucrose increased the number of FLI neurons in
      almost every subnucleus of the PBN (F((2,13)) = 7.610, P = 0.023), in addition to
      the caudal NST at the level of the area postrema (F((2,13)) = 10.777, P = 0.003)
      and the NST intermediate zone (F((2,13)) = 7.193, P = 0.014). No significant
      increase in the number of c-Fos positive neurons was detected in response to
      saccharin ingestion, although there was a trend towards a modest increase in a
      few select NST and PBN nuclei. These results suggest that the PBN and NST may be
      involved in sweet taste perception and modulation of sweet tastant intake, but
      the significantly enhanced intensity of Fos expression induced by sucrose
      indicates that PBN/NST neuronal activity is driven by the integrated effects of
      sweet taste sensation and post-ingestive signals.

PMID- 21964713
TI  - Treatment of severe acute pancreatitis through retroperitoneal laparoscopic
      drainage.
AB  - A treatment method based on drainage via retroperitoneal laparoscopy was adopted
      for 15 severe acute pancreatitis (SAP) patients to investigate the feasibility of
      the method. Ten patients received only drainage via retroperitoneal laparoscopy,
      four patients received drainage via both retroperitoneal and preperitoneal
      laparoscopy, and one patient received drainage via conversion to laparotomy.
      Thirteen patients exhibited a good drainage effect and were successfully cured
      without any other surgical treatment. Two patients had encapsulated effusions or
      pancreatic pseudocysts after surgery, but were successfully cured after lavage
      and B ultrasound-guided percutaneous catheter drainage. SAP treatment via
      retroperitoneal laparoscopic drainage is an effective surgical method, resulting
      in minor injury.

PMID- 21964714
TI  - "Fast Track" nasogastric decompression of rectal cancer surgery.
AB  - This study evaluates the application of fast track (FT) nasogastric decompression
      in patients who underwent anterior resection of rectal cancer. A randomized
      control trial was performed comparing the group with the fast track treatment (n
      = 57) and the group with traditional nasogastric decompression (n = 84).
      Preoperative characteristics and postoperative recovery indices were recorded and
      analyzed. The results indicate no significant differences in gender (P = 0.614),
      age (P = 0.653), tumor location (P = 0.113), and TNM stages (P = 0.054) were
      observed between the 2 groups. The differences in the type of resection,
      anastomosis, and adoption of protective colostomy were all not significant
      between the FT and the traditional group. During the first 24 hours after
      surgery, the volume of nasogastric drainage averaged 197 ml in the FT group and
      155 ml in the traditional group (P = 0.197). The initiation of test-meal (P =
      0.000), semiliquid diet (P = 0.002), and ordinary diet (P = 0.008) were all
      significantly shorter in the FT group. Furthermore, compared with the other
      group, the patients in the FT group enjoyed earlier removal of the abdominal
      drainage, urinary catheter, and shorter hospital stays (P = 0.000). Based on a
      correlation test, the duration of nasogastric decompression is related to the
      time of test-meal and semiliquid diet. The routine usage of nasogastric
      decompression in rectal surgery is unnecessary. The fast track procedure might
      help in facilitating postoperative functional and diet recovery, reducing the
      time of catheterization, and shortening hospital stay.

PMID- 21964715
TI  - Fertility outcome analysis after modified laparoscopic microsurgical tubal
      anastomosis.
AB  - Modified laparoscopic microsurgical tubal anastomosis is an alternative for
      microsurgical anastomosis via laparotomy to reverse sterilization in women with
      renewed child wish. The current study aims to evaluate the fertility outcome
      after modified laparoscopic microsurgical tubal anastomosis. A retrospective
      study was performed. Fifty-eight women who underwent modified laparoscopic
      microsurgical tubal anastomosis were monitored to investigate the fertility
      outcome and characteristics of this new technology. Of the 58 patients, the
      cumulative pregnancy rate (PR) in the 42 patients with follow-up data was 23.8%
      (10/42), 57.1% (24/42), 66.7% (28/42), and 73.8% (31/42) within 6, 12, 24, and 36
      months after surgery, respectively. The intrauterine PR was 69.0% (29/42). Two
      patients (4.8%) had ectopic pregnancies that occurred within 24 months of
      surgery; three cases ended in spontaneous abortion. The delivery rate was 83.9%
      (26/31). The length of operating time was 1.2+/-0.3 h, with a range of 1.0-2.5 h
      (60-145 min), and the mean time was approximately 75 min. The blood loss was
      relatively small, between 10 and 50 ml with an average amount of 22 ml. Thus, the
      modified laparoscopic tubal anastomosis is a highly successful procedure and a
      viable alternative to open abdominal microsurgical approaches. Compared with the
      traditional laparoscopic tubal sterilization reversal, this modified approach has
      three advantages: (1) less invasive approach via a trocar reduction; (2)
      remodeling of tube is better performing tied together after 3-4 sutures; and (3)
      faster operating time.

PMID- 21964716
TI  - Translating evidence into policy in China: opportunities and challenges.
AB  - Research and evidence are critical for the formulation of policies and practices
      in support of health care. In the past two decades, the Chinese Clinical
      Epidemiology Network has been promoting evidence-based policy making in China.
      Evidence-based policy has become a major part of the government's approach to
      policy making. The current article addresses the translation of evidence into
      health policies based on the expansion of evidence-based medicine in China. It
      also discusses the opportunities and challenges for certain evidence to be
      considered in policy making and practice in the future.

PMID- 21964718
TI  - Multiplexed pressure sensing with elastomer membranes.
AB  - We demonstrate a novel optical pressure measurement platform for microfluidics.
      The pressure sensors operate as pneumatically-tunable microlenses whose focal
      lengths vary with pressure. We show that pneumatic lens arrays can be used to
      perform sensitive multiplexed pressure measurements in microfluidic channels.

PMID- 21964719
TI  - Damage clusters after gamma irradiation of a nanoparticulate plasmid DNA peptide
      condensate.
AB  - We have gamma-irradiated plasmid DNA in aqueous solution in the presence of
      submillimolar concentrations of the ligand tetra-arginine. Depending upon the
      ionic strength, under these conditions, the plasmid can adopt a highly compacted
      and aggregated form which attenuates by some two orders of magnitude the yield of
      damage produced by the indirect effect. The yields of DNA single- and double
      strand breaks (SSB and DSB) which result are closely comparable with those
      produced in living cells. The radical lifetimes, diffusion distances, and track
      structure are expected to be similarly well reproduced. After irradiation, the
      aggregation was reversed by adjusting the ionic conditions. The approximate
      spatial distribution of the resulting DNA damage was then assayed by comparing
      the increases in the SSB and DSB yields produced by a subsequent incubation with
      limiting concentrations of the eukaryotic base excision repair enzymes
      formamidopyrimidine-DNA N-glycosylase (the FPG protein) and endonuclease III.
      Smaller increases in DSB yields were observed in the plasmid target that was
      irradiated in the condensed form. By modeling the spatial distribution of DNA
      damage, this result can be interpreted in terms of a greater extent of damage
      clustering.

PMID- 21964720
TI  - Merging the fields of mental health and social enterprise: lessons from abroad
      and cumulative findings from research with homeless youths.
AB  - Despite the growing integration of supported employment within the mental health
      system in the United States as well as the widespread use of social enterprises
      abroad, the fields of mental health and social enterprises remain largely
      separate in the USA. The mental health field currently lacks a response that
      strengthens homeless youths' existing human and social capital, provides them
      with marketable job skills and employment, and impacts their mental health. To
      address this gap, this paper establishes a case for using social enterprises with
      homeless youths, drawing on both global precedents and findings from a mixed
      methods study of a social enterprise intervention with homeless youths.
      Recommendations are offered for how to integrate social enterprises with mental
      health treatment as well as how to evaluate their impact on mental health
      outcomes.

PMID- 21964722
TI  - Social deprivation and prevalence of chronic kidney disease in the UK: workload
      implications for primary care.
AB  - BACKGROUND: The 'inverse care law' suggests that populations with the poorest
      health outcomes also tend to have poorer access to high-quality care. The new
      general practitioner (GP) contract in the UK aimed to reduce variations in care
      between areas by collecting information on processes and outcomes of chronic
      disease management. This study investigated whether, despite reductions in
      inequalities, primary care in deprived areas is still at a disadvantage due to
      the higher prevalence of chronic diseases, using chronic kidney disease (CKD) as
      an example. METHODS: Initially, data from a hospital-based cohort of CKD patients
      were analysed to investigate the clustering of CKD patients across area-level
      deprivation using a geographical information system that employed kernel density
      estimation. Data from the Quality and Outcomes Framework were then analysed to
      explore the burden of CKD and associated non-communicable chronic diseases (NCD)
      and assess the potential impact on GPs' workload by area-level deprivation.
      RESULTS: There was a significant clustering of CKD patients referred to the
      hospital in the most deprived areas. Both the prevalence of CKD and associated
      conditions and caseload per GP were significantly higher in deprived areas.
      CONCLUSION: In the most deprived areas, there is an increased burden of major
      chronic disease and a higher caseload for clinicians. These reflect significant
      differences in workload for practices in deprived areas, which needs to be
      addressed.

PMID- 21964721
TI  - Contribution of both M1 and M4 receptors to muscarinic agonist-mediated
      attenuation of the cocaine discriminative stimulus in mice.
AB  - RATIONALE: We previously showed that muscarinic agonists with M(1) and/or M(4)
      receptor affinities attenuated cocaine discrimination and self-administration in
      wild-type mice but not in M(1)/M(4) double-knockout mice. OBJECTIVE: This study
      aims to elucidate the respective contributions of M(1) and M(4) receptors to this
      effect. METHODS: Knockout mice lacking either the M(1) subtype (M (1) (-/-) ) or
      the M(4) subtype (M (4) (-/-) ) and wild-type mice were trained to discriminate
      10 mg/kg cocaine from saline. Muscarinic ligands were tested for modulation of
      cocaine discrimination: xanomeline (M(1)/M(4)-preferring agonist), VU0357017
      (M(1)-selective partial agonist), 77-LH-28-1 (M(1) agonist), and BQCA (M(1)
      selective positive allosteric modulator). RESULTS: Xanomeline produced rightward
      shifts in the cocaine dose-effect curve in all three genotypes, but most robustly
      in wild-type mice. VU0357017 produced rightward shifts in the cocaine dose-effect
      curve in wild-type and M (4) (-/-) mice, but not in M (1) (-/-) mice. Response
      rates were suppressed by xanomeline in wild-type and M (1) (-/-) but not in M (4)
      (-/-) mice and were unaltered by VU0357017. 77-LH-28-1 and BQCA also showed
      evidence of attenuating cocaine's discriminative stimulus, but at doses that
      suppressed responding or had other undesirable effects. Intriguingly, both
      VU0357017 and 77-LH-28-1 exhibited U-shaped dose-effect functions in attenuating
      cocaine discrimination. None of the drugs substituted for the cocaine stimulus.
      CONCLUSIONS: Attenuation of the cocaine stimulus by VU0357017 depended upon M(1)
      receptors, and full effects of xanomeline depended upon both M(1) and M(4)
      receptors. Therefore M(1)-selective agonists and mixed M(1)/M(4) agonists may be
      promising leads for developing medications that block cocaine's effects.

PMID- 21964723
TI  - Repeat testing is essential when estimating chronic kidney disease prevalence and
      associated cardiovascular risk.
AB  - BACKGROUND: Investigations into chronic kidney disease (CKD) and cardiovascular
      disease in the CKD population may be misleading as they are often based on a
      single test of kidney function. AIM: To determine whether repeat testing at 3
      months to confirm a diagnosis of CKD impacts on the estimated prevalence of CKD
      and the estimated 10-year general cardiovascular risk of the CKD population.
      DESIGN AND METHODS: Blood and urine samples from presumed healthy volunteers were
      analysed for evidence of CKD on recruitment and again 3 months later. Estimated
      10-year cardiovascular risk was calculated using criteria determined by the
      Framingham study. Preliminary study: 512 volunteers were screened for CKD. Of the
      initial results, 206 indicated CKD or eGFR within one standard deviation of
      abnormal, and 142 (69%) of these were retested. Validation study: 528 volunteers
      were recruited and invited to return for repeat testing. A total of 214 (40.5%)
      participants provided repeat samples. RESULTS: A single test indicating CKD had a
      positive predictive value of 0.5 (preliminary) and 0.39 (validation) for repeat
      abnormalities 3 months later. Participants with CKD confirmed on repeat testing
      had a significant increase in estimated 10-year cardiovascular risk over the
      population as a whole (preliminary: 16.5 vs. 11.9%, P < 0.05; validation: 18.1
      vs. 9.2%, P < 0.01). Participants with a solitary test indicating CKD had no
      elevation in cardiovascular risk. CONCLUSION: Repeat testing for CKD after 3
      months significantly reduces the estimated prevalence of disease and identifies a
      population with true CKD and a cardiovascular risk significantly in excess of the
      general population.

PMID- 21964724
TI  - 'End point' in the management of diabetic ketoacidosis.

PMID- 21964726
TI  - Jacalin interaction with human immunoglobulin A1 and bovine immunoglobulin G1:
      affinity constant determined by piezoelectric biosensoring.
AB  - The affinity of the D-galactose-binding lectin from Artocarpus heterophyllus
      lectin, known as jacalin, with immonuglobulins (Igs) was determined by
      biofunctionalization of a piezoelectric transducer. This piezoelectric
      biofunctionalized transducer was used as a mass-sensitive analytical tool,
      allowing the real-time binding analysis of jacalin-human immunoglobulin A1
      (IgA(1)) and jacalin-bovine IgG(1) interactions from which the apparent affinity
      constant was calculated. The strategy was centered in immobilizing jacalin on the
      gold electrode's surface of the piezoelectric crystal resonator using appropriate
      procedures based on self-assembling of 11-mercaptoundecanoic acid and 2
      mercaptoethanol thiol's mixture, a particular immobilization strategy by which it
      was possible to avoid cross-interaction between the proteins over electrode's
      surface. The apparent affinity constants obtained between jacalin-human IgA(1)
      and jacalin-bovine IgG(1) differed by 1 order of magnitude [(8.0 +/- 0.9) 10(5)
      vs (8.3 +/- 0.1) 10(6) L mol(-1)]. On the other hand, the difference found
      between human IgA(1) and human IgA(2) interaction with jacalin, eight times
      higher for IgA(1), was attributed to the presence of O-linked glycans in the
      IgA(1) hinge region, which is absent in IgA(2). Specific interaction of jacalin
      with O-glycans, proved to be present in the human IgA(1) and hypothetically
      present in bovine IgG(1) structures, is discussed as responsible for the obtained
      affinity values.

PMID- 21964725
TI  - Hybrid- and complex-type N-glycans are not essential for Newcastle disease virus
      infection and fusion of host cells.
AB  - N-linked glycans are composed of three major types: high-mannose (Man), hybrid or
      complex. The functional role of hybrid- and complex-type N-glycans in Newcastle
      disease virus (NDV) infection and fusion was examined in N
      acetylglucosaminyltransferase I (GnT I)-deficient Lec1 cells, a mutant Chinese
      hamster ovary (CHO) cell incapable of synthesizing hybrid- and complex-type N
      glycans. We used recombinant NDV expressing green fluorescence protein or red
      fluorescence protein to monitor NDV infection, syncytium formation and viral
      yield. Flow cytometry showed that CHO-K1 and Lec1 cells had essentially the same
      degree of NDV infection. In contrast, Lec2 cells were found to be resistant to
      NDV infection. Compared with CHO-K1 cells, Lec1 cells were shown to more
      sensitive to fusion induced by NDV. Viral attachment was found to be comparable
      in both lines. We found that there were no significant differences in the yield
      of progeny virus produced by both CHO-K1 and Lec1 cells. Quantitative analysis
      revealed that NDV infection and fusion in Lec1 cells were also inhibited by
      treatment with sialidase. Pretreatment of Lec1 cells with Galanthus nivalis
      agglutinin specific for terminal alpha1-3-linked Man prior to inoculation with
      NDV rendered Lec1 cells less sensitive to cell-to-cell fusion compared with mock
      treated Lec1 cells. Treatment of CHO-K1 and Lec1 cells with tunicamycin, an
      inhibitor of N-glycosylation, significantly blocked fusion and infection. In
      conclusion, our results suggest that hybrid- and complex-type N-glycans are not
      required for NDV infection and fusion. We propose that high-Man-type N-glycans
      could play an important role in the cell-to-cell fusion induced by NDV.

PMID- 21964727
TI  - Horse metabolism and the photocatalytic process as a tool to identify metabolic
      products formed from dopant substances: the case of sildenafil.
AB  - Two horses were treated with sildenafil, and its metabolic products were sought
      in both urine and plasma samples. Prior to this, a simulative laboratory study
      had been done using a photocatalytic process, to identify all possible main and
      secondary transformation products, in a clean matrix; these were then sought in
      the biological samples. The transformation of sildenafil and the formation of
      intermediate products were evaluated adopting titanium dioxide as photocatalyst.
      Several products were formed and characterized using the HPLC/HRMS(n) technique.
      The main intermediates identified in these experimental conditions were the same
      as the major sildenafil metabolites found in in vivo studies on rats and horses.
      Concerning horse metabolism, sildenafil and the demethylated product (UK 103,320)
      were quantified in blood samples. Sildenafil propyloxide, de-ethyl, and demethyl
      sildenafil, were the main metabolites quantified in urine. Some more oxidized
      species, already formed in the photocatalytic process, were also found in urine
      and plasma samples of treated animals. Their formation involved hydroxylation on
      the aromatic ring, combined oxidation and dihydroxylation, N-demethylation on the
      pyrazole ring, and hydroxylation. These new findings could be of interest in
      further metabolism studies.

PMID- 21964728
TI  - Dynamic physostigmine effects on hippocampus perfusion.
AB  - PURPOSE: To characterize the dynamic response of hippocampus blood flow to
      physostigmine infusion and to determine an infusion duration sufficiently long
      for robust detection of effects with arterial spin labeling (ASL) and
      sufficiently short to avoid peripheral side effects of physostigmine. MATERIALS
      AND METHODS: Two female (49 +/- 15 years) and nine male (53 +/- 13 years)
      subjects were studied to determine the time course of the physostigmine effect on
      hippocampus blood flow with ASL perfusion imaging during 20 minutes of baseline,
      30 minutes of physostigmine infusion at 1.0 mg/hr, and 70 minutes of recovery.
      RESULTS: Hippocampus perfusion decreased steadily over the course of the
      infusion, with the reduction in flow becoming significant after 20 minutes of
      infusion, reaching lowest levels near the end of infusion, and remaining
      significantly low and stable in the 70-minute recovery period. Percentage changes
      of hippocampus perfusion were -13.3%, -13.4%, and -13.4% for left, right, and
      bilateral hippocampus, respectively, at the end of infusion. CONCLUSION: At a
      dose rate of 1.0 mg/hr it is feasible to use an infusion time as short as 20
      minutes, performing perfusion imaging up to an hour after physostigmine infusion
      is discontinued, to minimize chances for adverse side effects.

PMID- 21964729
TI  - Ultrasound-guided bilateral brachial plexus blockade with propofol-ketamine
      sedation.
AB  - We report the use of ultrasound-guided bilateral brachial plexus block in a
      patient with bilateral radius fractures. An axillary block was performed on the
      patient's right and a supraclavicular block on her left using an in-plane (long
      axis) needle insertion technique. Into each side was injected 20 ml 0.5%
      ropivacaine, giving a total volume (dose) of 40 ml (200 mg). Provisions were made
      for rescue analgesia or unplanned conversion to general anesthesia during the
      operation, but these were not needed; furthermore, no perioperative complications
      were observed. General anesthesia has traditionally been used for simultaneous
      surgery involving the bilateral upper extremities because of concerns relating to
      local anesthetic toxicity, phrenic nerve blockade, and pneumothorax. The
      ultrasound-guided technique facilitates a reduction in the minimal effective
      volume of local anesthetic and can prevent potentially critical complications.
      Moreover, the technique can be performed within the recommended safe dose limits
      of the anesthetic, rendering it an important option for bilateral upper extremity
      surgery.

PMID- 21964730
TI  - Frequency-domain optical tomographic imaging of arthritic finger joints.
AB  - We are presenting data from the largest clinical trial on optical tomographic
      imaging of finger joints to date. Overall we evaluated 99 fingers of patients
      affected by rheumatoid arthritis (RA) and 120 fingers from healthy volunteers.
      Using frequency-domain imaging techniques we show that sensitivities and
      specificities of 0.85 and higher can be achieved in detecting RA. This is
      accomplished by deriving multiple optical parameters from the optical tomographic
      images and combining them for the statistical analysis. Parameters derived from
      the scattering coefficient perform slightly better than absorption derived
      parameters. Furthermore we found that data obtained at 600 MHz leads to better
      classification results than data obtained at 0 or 300 MHz.

PMID- 21964731
TI  - The role of Klebsiella pneumoniae rmpA in capsular polysaccharide synthesis and
      virulence revisited.
AB  - Klebsiella pneumoniae community-acquired pyogenic liver abscess (PLA) is an
      emerging infectious disease. The rmpA gene (for regulator of mucoid phenotype A)
      has been reported to be associated with PLA in prevalence studies. NTUH-K2044, a
      K1 PLA isolate, carries three rmpA/A2 genes: two large-plasmid-carried genes (p
      rmpA and p-rmpA2) and one chromosomal gene (c-rmpA). In this study, we re
      examined the role of rmpA/A2 in PLA pathogenesis to clarify the relationship of
      rmpA/A2 and capsular serotype to virulence. Using isogenic gene deletion strains
      and complemented strains of NTUH-K2044, we demonstrated that only p-rmpA enhanced
      expression of capsular polysaccharide synthesis (cps) genes and capsule
      production. Nevertheless, the lethal dose and in vivo competitive index indicated
      that p-rmpA does not promote virulence in mice. The prevalence of these three
      rmpA/A2 and capsular types in 206 strains was investigated. This revealed a
      correlation of rmpA/A2 with six PLA-related capsular types (K1, K2, K5, K54, K57
      and KN1). However, the correlation of rmpA/A2 with K1 strains from the West was
      less obvious than with the strains from Asia (17/22 vs 39/39, P = 0.0019). Among
      the three rmpA/A2 genes, p-rmpA was the most prevalent. Due to the strong
      correlation with PLA-related capsular types, p-rmpA could serve as a surrogate
      marker for PLA. We found an association of p-rmpA with three widely spaced loci
      in a large plasmid (30/32). Therefore, rmpA could be co-inherited together with
      virulence genes carried by this plasmid.

PMID- 21964733
TI  - PrcR, a PucR-type transcriptional activator, is essential for proline utilization
      and mediates proline-responsive expression of the proline utilization operon
      putBCP in Bacillus subtilis.
AB  - The soil bacterium Bacillus subtilis can utilize exogenous proline as a sole
      nitrogen or carbon source. The proline-inducible putBCP (formerly ycgMNO) operon
      encodes proteins responsible for proline uptake and two-step oxidation of proline
      to glutamate. We now report that a gene (formerly ycgP, now designated prcR)
      located downstream of the putBCP operon is essential for B. subtilis cells to
      utilize proline as a sole nitrogen or carbon source. Disruption of the prcR gene
      also abolished proline induction of putB transcription. prcR expression is not
      subject to autoregulation and proline induction. The PrcR protein shows no
      significant amino acid sequence similarity to the known transcriptional
      activators for proline utilization genes of other bacteria, but it does show
      partial amino acid sequence similarity to the transcriptional regulator PucR for
      the purine degradation genes of B. subtilis. PrcR orthologues of unknown function
      are present in some other Bacillus species. Primer-extension analysis suggests
      that both putB and prcR are transcribed by a sigma(A)-dependent promoter.
      Deletion and mutation analysis revealed that an inverted repeat (5'-TTGTGG-N5
      CCACAA-3') centred at position -76 relative to the transcriptional initiation
      site of putB is essential for putB expression. Electrophoretic mobility shift
      assays showed that the purified His-tagged PrcR was capable of binding
      specifically to this inverted repeat. Altogether, these results suggest that PrcR
      is a PucR-type transcriptional activator that mediates expression of the B.
      subtilis putBCP operon in response to proline availability.

PMID- 21964734
TI  - Trichoderma: sensing the environment for survival and dispersal.
AB  - Species belonging to the genus Trichoderma are free-living fungi common in soil
      and root ecosystems, and have a broad range of uses in industry and agricultural
      biotechnology. Some species of the genus are widely used biocontrol agents, and
      their success is in part due to mycoparasitism, a lifestyle in which one fungus
      is parasitic on another. In addition Trichoderma species have been found to
      elicit plant defence responses and to stimulate plant growth. In order to survive
      and spread, Trichoderma switches from vegetative to reproductive development, and
      has evolved with several sophisticated molecular mechanisms to this end. Asexual
      development (conidiation) is induced by light and mechanical injury, although the
      effects of these inducers are influenced by environmental conditions, such as
      nutrient status and pH. A current appreciation of the links between the molecular
      participants is presented in this review. The photoreceptor complex BLR-1/BLR-2,
      ENVOY, VELVET, and NADPH oxidases have been suggested as key participants in this
      process. In concert with these elements, conserved signalling pathways, such as
      those involving heterotrimeric G proteins, mitogen-activated protein kinases
      (MAPKs) and cAMP-dependent protein kinase A (cAMP-PKA) are involved in this
      molecular orchestration. Finally, recent comparative and functional genomics
      analyses allow a comparison of the machinery involved in conidiophore development
      in model systems with that present in Trichoderma and a model to be proposed for
      the key factors involved in the development of these structures.

PMID- 21964732
TI  - CcpA coordinates central metabolism and biofilm formation in Staphylococcus
      epidermidis.
AB  - Staphylococcus epidermidis is an opportunistic bacterium whose infections often
      involve the formation of a biofilm on implanted biomaterials. In S. epidermidis,
      the exopolysaccharide facilitating bacterial adherence in a biofilm is
      polysaccharide intercellular adhesin (PIA), whose synthesis requires the enzymes
      encoded within the intercellular adhesin operon (icaADBC). In vitro, the
      formation of S. epidermidis biofilms is enhanced by conditions that repress
      tricarboxylic acid (TCA) cycle activity, such as growth in a medium containing
      glucose. In many Gram-positive bacteria, repression of TCA cycle genes in
      response to glucose is accomplished by catabolite control protein A (CcpA). CcpA
      is a member of the GalR-LacI repressor family that mediates carbon catabolite
      repression, leading us to hypothesize that catabolite control of S. epidermidis
      biofilm formation is indirectly regulated by CcpA-dependent repression of the TCA
      cycle. To test this hypothesis, ccpA deletion mutants were constructed in strain
      1457 and 1457-acnA and the effects on TCA cycle activity, biofilm formation and
      virulence were assessed. As anticipated, deletion of ccpA derepressed TCA cycle
      activity and inhibited biofilm formation; however, ccpA deletion had only a
      modest effect on icaADBC transcription. Surprisingly, deletion of ccpA in strain
      1457-acnA, a strain whose TCA cycle is inactive and where icaADBC transcription
      is derepressed, strongly inhibited icaADBC transcription. These observations
      demonstrate that CcpA is a positive effector of biofilm formation and icaADBC
      transcription and a repressor of TCA cycle activity.

PMID- 21964735
TI  - Dynamic regulation of mitochondrial respiratory chain efficiency in Saccharomyces
      cerevisiae.
AB  - To adapt to changes in the environment, cells have to dynamically alter their
      phenotype in response to, for instance, temperature and oxygen availability.
      Interestingly, mitochondrial function in Saccharomyces cerevisiae is inherently
      temperature sensitive; above 37  degrees C, yeast cells cannot grow on
      respiratory carbon sources. To investigate this phenomenon, we studied the effect
      of cultivation temperature on the efficiency (production of ATP per atom of
      oxygen consumed, or P/O) of the yeast respiratory chain in glucose-limited
      chemostats. We determined that even though the specific oxygen consumption rate
      did not change with temperature, oxygen consumption no longer contributed to
      mitochondrial ATP generation at temperatures higher than 37  degrees C.
      Remarkably, between 30 and 37  degrees C, we observed a linear increase in
      respiratory efficiency with growth temperature, up to a P/O of 1.4, close to the
      theoretical maximum that can be reached in vivo. The temperature-dependent
      increase in efficiency required the presence of the mitochondrial glycerol-3
      phosphate dehydrogenase GUT2. Respiratory chain efficiency was also altered in
      response to changes in oxygen availibility. Our data show that, even in the
      absence of alternative oxidases or uncoupling proteins, yeast has retained the
      ability to dynamically regulate the efficiency of coupling of oxygen consumption
      to proton translocation in the respiratory chain in response to changes in the
      environment.

PMID- 21964736
TI  - Randomized clinical trial of laparoendoscopic single-site versus conventional
      laparoscopic cholecystectomy.
AB  - BACKGROUND: Conventional laparoscopy with three or more ports remains the 'gold
      standard' for cholecystectomy, but a laparoendoscopic single-site (LESS) approach
      is emerging, designed to decrease parietal trauma and improve cosmesis. This
      study compared conventional laparoscopic (CL) with LESS cholecystectomy, with
      short-term clinical results as the main outcomes. METHODS: A randomized trial of
      CL and LESS cholecystectomies involving 150 patients was undertaken. Follow-up
      was for 1 month after surgery. The primary endpoint was body image results
      evaluated by means of validated scales. Secondary endpoints were: postoperative
      pain measured on a visual analogue scale, analgesia requirement, morbidity,
      quality of life (QoL) measured with Short Form 12, duration of operation,
      hospital stay, time to return to work and cost analysis. RESULTS: Operating times
      and complications were similar in the two groups. Two LESS procedures (3 per
      cent) were converted to two-port laparoscopy owing to difficulties with exposure,
      and one CL operation was achieved through a single port because extensive fibrous
      peritoneal adhesions prevented placement of other ports. There were three and
      four port-site seroma/haematomas in the LESS and CL groups respectively. Better
      pain profiles and lower analgesia requirements were recorded in the LESS group (P
      < 0.001). QoL, body image and scar scale results were also better (P < 0.001).
      Operative costs were higher for LESS procedures (P < 0.001), although median time
      to return to work was shorter (P = 0.003). CONCLUSION: LESS is an alternative to
      CL cholecystectomy associated with better cosmesis, body image, QoL and an
      improved postoperative pain profile.

PMID- 21964737
TI  - Reactive oxygen species and permeability transition pore in rat liver and kidney
      mitoplasts.
AB  - Mitochondrial permeability transition is typically characterized by Ca(2+) and
      oxidative stress-induced opening of a nonselective proteinaceous membrane pore
      sensitive to cyclosporin A, known as the permeability transition pore (PTP). Data
      from our laboratory provide evidence that the PTP is formed when inner membrane
      proteins aggregate as a result of disulfide cross-linking caused by thiol
      oxidation. Here we compared the redox properties between PTP in intact
      mitochondria and mitoplasts. The rat liver mitoplasts retained less than 5% and
      10% of the original outer membrane markers monoamine oxidase and VDAC,
      respectively. Kidney mitoplasts also showed a partial depletion of hexokinase. In
      line with the redox nature of the PTP, mitoplasts that were more susceptible to
      PTP opening than intact mitochondria showed higher rates of H(2)O(2) generation
      and decreased matrix NADPH-dependent antioxidant activity. Mitoplast PTP was also
      sensitive to the permeability transition inducer tert-butyl hydroperoxide and to
      the inhibitors cyclosporin A, EGTA, ADP, dithiothreitol and catalase. Taken
      together, these data indicate that, in mitoplasts, PTP exhibits redox regulatory
      characteristics similar to those described for intact mitochondria.

PMID- 21964738
TI  - A randomized trial on the efficacy of methylphenidate and modafinil for improving
      cognitive functioning and symptoms in patients with a primary brain tumor.
AB  - Limited research is available regarding the efficacy of psychostimulants in
      treating cognitive function in primary brain tumor patients. An open-label,
      randomized, pilot trial examined both the general and differential efficacy of 4
      weeks of methylphenidate (MPH) and modafinil (MOD) in 24 brain tumor patients.
      Participants completed cognitive tests and self-report measures of fatigue, sleep
      disturbance, mood and quality of life at baseline and after 4 weeks.Following
      stimulant treatment, there was evidence of a beneficial effect on test
      performance in speed of processing and executive function requiring divided
      attention. Patients with the greatest deficit in executive function at baseline
      appeared to derive the greatest benefit following stimulant therapy.
      Inconsistent, differential effects were found on a measure of attention in favor
      of MPH and on a measure of processing speed in favor of MOD. There was also
      evidence of a general beneficial effect on patient-reported measures of fatigue,
      mood, and quality of life, with no statistically significant differences between
      treatment arms in these measures over time. The results from this small pilot
      study should be interpreted with caution, but appear to warrant additional
      research, in larger study samples, targeting fatigue, processing speed and
      executive function, and exploring different doses of stimulants. Future studies
      may also wish to explore the specific patient factors that may be associated with
      responsiveness to psychostimulant treatment.

PMID- 21964739
TI  - uPAR and cathepsin B downregulation induces apoptosis by targeting calcineurin A
      to BAD via Bcl-2 in glioma.
AB  - Cathepsin B and urokinase plasminogen activator receptor (uPAR) are postulated to
      play key roles in glioma invasion. Calcineurin is one of the key regulators of
      mitochondrial-dependent apoptosis, but its mechanism is poorly understood. Hence,
      we studied subcellular localization of calcineurin after transcriptional
      downregulation of uPAR and cathepsin B in glioma. In the present study, efficient
      downregulation of uPAR and cathepsin B increased the translocation of calcineurin
      A from the mitochondria to the cytosol, decreased pBAD (S136) expression and its
      interaction with 14-3-3zeta and increased the interaction of BAD with Bcl-xl. Co
      depletion of uPAR and cathepsin B induced mitochondrial translocation of BAD,
      activation of caspase 3 as well as PARP and cytochrome c and SMAC release. These
      effects were inhibited by FK506 (10 MUM), a specific inhibitor of calcineurin.
      Calcineurin A was co-localized and also co-immunoprecipitated with Bcl-2. This
      interaction decreased with co-depletion of uPAR and cathepsin B and also with Bcl
      2 inhibitor, HA 14-1 (20 MUg/ml). Altered localization and interaction of
      calcineurin A with Bcl-2 was also observed in vivo when uPAR and cathepsin B were
      downregulated. In conclusion, downregulation of uPAR and cathepsin B induced
      apoptosis by targeting calcineurin A to BAD via Bcl-2 in glioma.

PMID- 21964740
TI  - Metastatic glioblastoma: case presentations and a review of the literature.
AB  - Extracranial metastases from glioblastoma (GBM) are uncommon with an estimated
      incidence of less than 2%. We report two cases of metastatic GBM seen within an 8
      week period followed by a literature review. We attempted to identify common
      factors or a causative mechanism. Factors that predominated among the reviewed
      cases included male gender, tumor location, and younger age. Causative mechanisms
      were not apparent. While metastatic disease remains rare, it might be occurring
      with increasing frequency. This trend might be due to increased diagnosis, better
      imaging, a more extensive physician workup, or an increase in survival.
      Metastatic GBM can present and progress quite rapidly, and repeat evaluations of
      persistent or worsening complaints among GBM patients are warranted. Early
      diagnosis of metastatic disease spread can help to expedite alleviation of
      patients' discomfort, in an already aggressive disease process.

PMID- 21964741
TI  - Yessotoxin induces apoptosis in HL7702 human liver cells.
AB  - The marine toxin yessotoxin (YTX) is found in numerous aquatic environments and
      poses a potential threat to the shellfish industry and to public health. We
      analyzed the toxicity of YTX on HL7702 human liver cells using optical
      microscopy, Hoechst 33342 chromatin staining, DNA gel electrophoresis, rhodamine
      123 staining and calcium-sensitive laser scanning confocal microscopy. The
      results demonstrated that YTX induced the usual hallmarks of apoptosis, including
      chromatin condensation, DNA laddering, activity of caspase-3 deregulation and
      loss of mitochondrial membrane potential. Furthermore, YTX caused cytosolic
      calcium levels to increase in HL7702 cells. YTX may cause liver damage through
      hepatocyte apoptosis.

PMID- 21964742
TI  - Elevated levels of endothelin-1 in hepatic venous blood are associated with
      intrapulmonary vasodilatation in humans.
AB  - BACKGROUND: Hepatopulmonary syndrome is a pulmonary vascular complication of
      cirrhosis in which intrapulmonary vasodilatation (IPV) results in hypoxemia.
      Endothelin-1 (ET-1), produced by proliferating cholangiocytes, has been
      identified as a mediator of IPV in an animal model of HPS, but the
      pathophysiology of IPV in humans has not been defined. AIM: The purpose of this
      study was to assess whether cirrhosis with IPV, which often leads to HPS, is
      associated with increased hepatic venous ET-1 blood levels. METHODS: We performed
      a prospective cohort pilot study of 40 patients with liver disease undergoing
      transjugular liver biopsy from November 1, 2008 to September 1, 2009. Patients
      were categorized according to absence (-) or presence (+) of IPV as determined by
      bubble-contrasted echocardiography. Hepatic venous blood was assayed for ET-1 by
      ELISA. The percent volume of cholangiocytes in the liver biopsy specimen was
      determined by morphometric analysis, as a measure of bile duct proliferation.
      RESULTS: Nine subjects were excluded, due to absence of cirrhosis (6) and patent
      foramen ovale (3). Of the remaining 31 subjects, IPV was present in 18 (58%).
      Median hepatic venous ET-1 was higher with IPV+ than IPV- at levels of 9.1 pg/mL
      (range 7.5-11.7) versus 2.1 pg/mL (1.3-5.6), respectively (P = 0.004). ET-1
      levels correlated positively with cholangiocyte percent volume (r = 0.72, P <
      0.001) but not with measures of liver dysfunction (bilirubin, INR, MELD score, or
      hepatic venous pressure gradient). CONCLUSION: In human cirrhosis, increased
      hepatic venous ET-1 is associated with IPV and increased hepatic cholangiocyte
      volume.

PMID- 21964744
TI  - Complex distal 10q rearrangement in a girl with mild intellectual disability:
      follow up of the patient and review of the literature of non-acrocentric
      satellited chromosomes.
AB  - We report on an intellectually disabled girl with a de novo satellited chromosome
      10 (10qs) and performed a review of the literature of the non-acrocentric
      satellited chromosomes (NASC). Satellites and stalks normally occur on the short
      arms of acrocentric chromosomes; however, the literature cites several reports of
      satellited non-acrocentric chromosomes, which presumably result from a
      translocation with an acrocentric chromosome. This is, to our knowledge, the
      third report of a 10qs chromosome. The phenotype observed in the proband prompted
      a search for a structural rearrangement of chromosome 10q. By microsatellite
      analysis we observed a 4 Mb deletion on the long arm of chromosome 10,
      approximately 145 kb from the telomere. FISH and array CGH analyses revealed a
      complex rearrangement involving in range from the centromere to the telomere: A
      9.64 Mb 10q26.11-q26.2 duplication, a 1.3 Mb region with no copy number change,
      followed by a 5.62 Mb 10q26.2-q26.3 deletion and a translocation of satellite
      material. The homology between the repeat sequences at 10q subtelomere region and
      the sequences on the acrocentric short arms may explain the origin of the
      rearrangement and it is likely that the submicroscopic microdeletion and
      microduplication are responsible for the abnormal phenotype in our patient. The
      patient presented here, with a 15-year follow-up, manifests a distinct phenotype
      different from the 10q26 pure distal monosomy and trisomy syndromes.

PMID- 21964743
TI  - EUS-FNA for pancreatic neuroendocrine tumors: a tertiary cancer center
      experience.
AB  - OBJECTIVES: Pancreatic neuroendocrine tumors (PNET) are fairly uncommon. Recent
      data highlight the importance of EUS in diagnosis of PNET. With this background,
      we decided to review our experience from a tertiary cancer center with regard to
      the presentation and clinical features of PNET and the diagnostic utility of EUS
      FNA in this scenario. METHODS: We identified patients who underwent EUS at our
      institution between January 1st 2001 and December 31st 2009 for a suspected PNET.
      Data on clinical features, cross-sectional imaging findings, EUS findings, and
      cytology results were collected. RESULTS: A total of 81 patients were referred
      for EUS-FNA for a suspected PNET. Mean age was 58.1 years. There were 41 (50.6%)
      males. PNET was found incidentally in 38 (46.9%) patients. Computed tomography
      scanning identified a pancreatic mass in 72 out of 79 (91.1%) cases. Mean
      diameter of the largest lesion seen on EUS was 27.5 mm (range: 6.9-80 mm). The
      most common site (34; 42%) was the head of the pancreas. EUS-FNA correctly
      confirmed a PNET in 73 out of 81 cases with diagnostic accuracy of 90.1%. Seven
      (8.6%) out of 81 patients had functional lesions, including three gastrinomas and
      four insulinomas. Liver metastases were found in 31 out of 81 (38.3%) cases. Of
      the 31 patients with liver metastasis, the mean diameter of lesions on EUS was
      33.9 mm compared with 23.5 mm in patients without liver metastasis (P = 0.005).
      CONCLUSION: EUS-FNA is a reliable modality for further characterization of
      suspected lesions and for establishing a tissue diagnosis. The occurrence of
      complications of EUS-FNA in this setting is low. Non-functional PNET are more
      frequently encountered than functional PNET.

PMID- 21964745
TI  - Single-stage reconstruction of skin-involving nasal paraffinoma with
      pericraniosubgaleal flap.
AB  - BACKGROUND: The removal of a paraffinoma over the nasal bridge may result in
      thinning and even loss of involved skin as well as a saddle nose deformity. For
      nasal reconstruction, a variety of techniques using a free graft of autogenous
      tissue such as fascia, dermofat, or cartilage have been used, either in
      immediate, single-stage or in delayed, multiphase treatment. However, such
      reconstructions can be challenging largely due to absorption of the grafted
      tissue and poor blood supply to the surrounding nasal tissue infiltrated with
      paraffin. This article reports the successful clinical outcomes of immediate,
      single-stage reconstructions by wrapping a pericraniosubgaleal flap over the
      nasal implant after removing a paraffinoma. METHODS: Eleven patients with a
      paraffinoma showing a palpable lump, redness, or telangiectasia over the nasal
      skin were treated between November 1998 and March 2011. The mean follow-up period
      was 20.1 months. As much of the paraffinoma as possible was removed via a
      bidirectional approach (open rhinoplasty and frontal hairline incision), and the
      resulting deformity was reconstructed simultaneously using a pericraniosubgaleal
      flap and turning it over the sculpted nasal implant (ePTFE; GORE-TEX((r)) in nine
      cases and silicone in two cases). RESULTS: Nine patients (81.8%) were treated
      successfully without complications and were satisfied with their results.
      However, the other two patients complained of incomplete removal of the
      paraffinoma requiring additional removal. Telangiectasia over the nose improved
      in four out of six patients after surgery. CONCLUSION: Nasal reconstruction using
      a pericraniosubgaleal flap is one of the most reliable surgical options for
      treating skin-involving nasal paraffinomas. The advantage of such a method is
      that a well-vascularized and durable flap, which is resistant to infection, is
      wrapped over the sculpted nasal implant in a single step. It also reinforces the
      thinned skin, which makes it easier to form various shapes, producing excellent
      cosmetic results. Finally, it can also serve as a tolerable graft bed in the case
      of overlying skin loss.

PMID- 21964747
TI  - Coenzyme Q10 does not enhance preadipocyte viability in an in vitro lipotransfer
      model.
AB  - BACKGROUND: Autologous fat is an attractive soft-tissue filler in plastic and
      reconstructive surgery. The success of the procedure relies strongly on the
      technique of transferring viable preadipocytes. Among other factors, preadipocyte
      viability is impaired by local anesthetics. Application of coenzyme Q10 is being
      performed by aesthetic plastic surgeons to enhance the success of lipotransfer.
      The aim of this study was to evaluate the effect of Q10 on preadipocyte viability
      with special regard to impairment after lidocaine treatment. METHODS:
      Preadipocytes were pretreated with coenzyme Q10 or vehicle control followed by
      incubation with lidocaine for 30 min. Viability and apoptosis were assessed by
      FACS analysis and Western blot. RESULTS: Coenzyme Q10 did not improve viability
      nor have any effect on investigated apoptosis parameters. Preadipocyte viability
      was reduced after lidocaine treatment. Surface binding of annexin V, cleavage of
      caspase-3, and abundance of subdiploid cells were not detectable though,
      suggesting that necrosis rather than apoptosis is the cause for reduced
      preadipocyte viability. CONCLUSION: Our results indicate that Q10 does not
      improve preadipocyte viability. Preadipocyte cell death induced by lidocaine is
      not caused by apoptosis but by necrosis, which cannot be prevented by coenzyme
      Q10. These findings should be taken into account when searching for solutions to
      improve preadipocyte viability in the context of soft tissue engineering and
      autologous fat transfer.

PMID- 21964746
TI  - Effective wound closure with a new two-component wound closure device (PrineoTM)
      in excisional body-contouring surgery: experience in over 200 procedures.
AB  - BACKGROUND: In excisional body-contouring surgery the surgeon is often confronted
      with time-consuming closure of long wounds. Recently, a new combination of a self
      adhering mesh together with a liquid 2-octyl cyanoacrylate adhesive (PrineoTM;
      Ethicon, Inc., Somerville, NJ, USA) has been introduced to replace intracutaneous
      running suture. METHODS: An observational study was undertaken to evaluate the
      efficacy of the new wound closure device in excisional body-contouring procedures
      between January 2008 and November 2010. Wound characteristics were recorded in a
      prospectively maintained database. RESULTS: During the study period, 224
      procedures in 180 patients were undertaken. Twenty-seven patients had two
      subsequent operations and four patients had three subsequent operations.
      Application of the new device was easy and safe and patient satisfaction with the
      results was generally high. However, intense local allergic reactions were seen
      in 4 patients (1.8%), which necessitated early removal and topical corticosteroid
      treatment. CONCLUSIONS: PrineoTM enables the surgeon to perform a quick and
      smooth skin closure, especially in long incisions frequently encountered in
      excisional body-contouring surgery. The application is fast and easy if basic
      guidelines are respected. Operating time is saved by eliminating the need for
      time-consuming intracutaneous running sutures. Removal is easy and painless for
      the patient. However, there is a potential for local allergic adverse effects of
      which the surgeon must be aware.

PMID- 21964748
TI  - Bubble cell for magnetic bead trapping in capillary electrophoresis.
AB  - A bubble cell capillary classically used to extend the optical path length for UV
      vis detection is employed here to trap magnetic beads. With this system, a large
      amount of beads can be captured without inducing a strong pressure drop, as it is
      the case with magnetic beads trapped in a standard capillary, thereby having less
      effect on the experimental conditions. Using numerical simulations and
      microscopic visualizations, the capture of beads inside a bubble cell was
      investigated with two magnet configurations. Pressure-driven and electro-osmotic
      flow velocities were measured for different amounts of protein-A-coated beads or
      C18-functionalized beads (RPC-18). Solid-phase extraction of a model antibody on
      protein-A beads and preconcentration of fluorescein on RPC-18 beads were
      performed as proof of concept experiments.

PMID- 21964749
TI  - In and out of the belly of the beast.

PMID- 21964751
TI  - Late-stage neurosyphilis presenting with severe neuropsychiatric deficits:
      diagnosis, therapy, and course of three patients.
AB  - Neurosyphilis is an infectious disease that has reappeared over the past two
      decades. It is caused by Treponema pallidum subspecies pallidum that can affect
      the central nervous system (CNS) during any stage of the disease. Besides early
      CNS involvement predominantly presenting with symptoms of meningitis, a
      parenchymal affection of the brain leading to severe neuropsychiatric symptoms
      particularly emerges at later stages, but is rarely seen nowadays due to early
      antibiotic treatment. Together with the clinical findings, a characteristic
      combination of serological and cerebrospinal fluid (CSF) abnormalities leads to
      the diagnosis of neurosyphilis and is required to assess its activity. However,
      particularly at later stages of disease and after antibiotic treatment,
      serological and CSF abnormalities may become ambiguous and, therefore, difficult
      to interpret. This can be accompanied by persisting or fluctuating
      neuropsychological deficits. To this day, no well-controlled clinical data exists
      concerning the treatment of late-stage neurosyphilis, neither on type, optimal
      dosage, duration, and long-term efficacy of antibiotic therapy. Therefore,
      treatment and follow-up of late-stage neurosyphilis are challenging tasks. Here,
      we present three cases of neurosyphilis with severe neuropsychiatric symptoms in
      non-immunocompromised patients and a review of the recent literature.

PMID- 21964750
TI  - Neurorehabilitation of stroke.
AB  - Despite ongoing improvements in the acute treatment of cerebrovascular diseases
      and organization of stroke services, many stroke survivors are in need of
      neurorehabilitation, as more than two-thirds show persisting neurologic deficits.
      While early elements of neurorehabilitation are already taking place on the
      stroke unit, after the acute treatment, the patient with relevant neurologic
      deficits usually takes part in an organized inpatient multidisciplinary
      rehabilitation program and eventually continues with therapies in an ambulatory
      setting afterwards. A specialized multidisciplinary neurorehabilitation team with
      structured organization and processes provides a multimodal, intense treatment
      program for stroke patients which is adapted in detail to the individual goals of
      rehabilitation. There are many parallels between postlesional neuroplasticity
      (relearning) and learning in the development of individuals as well as task
      learning of healthy persons. One key principle of neurorehabilitation is the
      repetitive creation of specific learning situations to promote mechanisms of
      neural plasticity in stroke recovery. There is evidence of achieving a better
      outcome of neurorehabilitation with early initiation of treatment, high
      intensity, with specific goals and active therapies, and the coordinated work and
      multimodality of a specialized team. In this context, interdisciplinary goal
      setting and regular assessments of the patient are important. Furthermore,
      several further potential enhancers of neural plasticity, e.g., peripheral and
      brain stimulation techniques, pharmacological augmentation, and use of robotics,
      are under evaluation.

PMID- 21964752
TI  - Intracranial spreading of a spinal anaplastic astrocytoma.

PMID- 21964753
TI  - Upbeat nystagmus as a clinical sign of physostigmine-induced right occipital non
      convulsive status epilepticus.

PMID- 21964754
TI  - Ipsilateral reversible diaphragmatic paralysis after pons stroke.

PMID- 21964755
TI  - Correspondence of human visual areas identified using functional and anatomical
      MRI in vivo at 7 T.
AB  - PURPOSE: To study the correspondence of anatomically and functionally defined
      visual areas (primary visual cortex, V1, and motion selective area V5/human MT+)
      by using structural magnetic resonance imaging (MRI) and functional MRI (fMRI) in
      vivo at 7 T. MATERIALS AND METHODS: Four subjects participated in this study.
      High-resolution (~0.4 mm isotropic) anatomical MRI was used to identify cortical
      regions based on their distinct cortical lamination. The optimal contrast for
      identifying heavily myelinated layers within gray matter was quantitatively
      assessed by comparing T(1)-weighted magnetization-prepared rapid gradient echo
      (MPRAGE) and T(2)*-weighted, 3D fast-low angle shot (FLASH) imaging. Retinotopic
      mapping was performed using GE-based fMRI at 1.5 mm isotropic resolution to
      identify functional areas. RESULTS: T(2)*-weighted FLASH imaging was found to
      provide a significantly higher contrast-to-noise ratio, allowing visualization of
      the stria of Gennari in every slice of a volume covering the occipital cortex in
      each of the four subjects in this study. The independently derived boundary of
      V1, identified in the same subjects using retinotopic mapping by fMRI, closely
      matched the border of anatomically defined striate cortex in the human brain.
      Evidence of banding was also found within the functionally defined V5 area;
      however, we did not find a good correlation of this area, or the functionally
      identified subregion (MT), with the banded area. CONCLUSION: High-resolution
      T(2)*-weighted images acquired at 7 T can be used to identify myelinated bands
      within cortical gray matter in reasonable measurement times. Regions where a
      myelinated band was identified show a high degree of overlap with the
      functionally defined V1 area.

PMID- 21964756
TI  - Negative regulation of HIF-1alpha by an FBW7-mediated degradation pathway during
      hypoxia.
AB  - Hypoxia inducible factor-1alpha (HIF-1alpha) stimulates expression of genes
      associated with angiogenesis and is associated with poor outcomes in ovarian and
      other cancers. In normoxia, HIF-1alpha is ubiquitinated and degraded through the
      E3 ubiquitin ligase, von Hippel-Lindau; however, little is known about the
      regulation of HIF-1alpha in hypoxic conditions. FBW7 is an E3 ubiquitin ligase
      that recognizes proteins phosphorylated by glycogen synthase kinase 3beta
      (GSK3beta) and targets them for destruction. This study used an ovarian cancer
      cell model to test the hypothesis that HIF-1alpha phosphorylation by GSK3beta in
      hypoxia leads to interaction with FBW7 and ubiquitin-dependent degradation.
      Expression of constitutively active GSK3beta reduced HIF-1alpha protein and
      transcriptional activity and increased ubiquitination of HIF-1alpha in hypoxia,
      whereas pharmacologic inhibition of GSK3 or expression of siGSK3beta promoted HIF
      1alpha stabilization and activity. A mechanism through FBW7 was supported by the
      observed decrease in HIF-1alpha stabilization when FBW7 was overexpressed and
      both the elevation of HIF-1alpha levels and decrease in ubiquitinated HIF-1alpha
      when FBW7 was suppressed. Furthermore, HIF-1alpha associated with FBW7gamma by co
      immunoprecipitation, and the interaction was weakened by inhibition of GSK3 or
      mutation of GSK3beta phosphorylation sites. The relevance of this pathway to
      angiogenic signaling was supported by the finding that endothelial cell tube
      maturation was increased by conditioned media from hypoxic SK-OV-3 cell lines
      expressing suppressed GSK3beta or FBW7. These data introduce a new mechanism for
      regulation of HIF-1alpha during hypoxia that utilizes phosphorylation to target
      HIF-1alpha for ubiquitin-dependent degradation through FBW7 and may identify new
      targets in the regulation of angiogenesis.

PMID- 21964757
TI  - Development of a flow cytometric immunoassay for recombinant bovine somatotropin
      induced antibodies in serum of dairy cows.
AB  - Administration of recombinant bovine somatotropin (rbST) to enhance milk
      production in dairy cows is banned within the European Union. Therefore, methods
      for pinpointing rbST abuse are required. Due to the problematic detection of rbST
      itself in serum, methods are also focused on detecting changes in rbST-related
      biomarkers. In this study, a fast and easy-to-perform microsphere-based flow
      cytometric immunoassay (FCIA) for detection of rbST-induced antibodies in serum
      was developed. Until now, detection of rbST-induced antibodies was also
      problematic due to non-specific binding of serum proteins resulting in a high
      rate of false positive results. Therefore, five different sample preparation
      methods, i.e. dilution, octanoic acid precipitation, filtration, protein G
      purification, and a previously described generic FCIA sample preparation were
      critically compared to overcome non-specific binding to the microspheres. Only
      the generic FCIA sample pretreatment was effective in reducing non-specific
      binding. As a result, an absolute decision level for detecting rbST antibodies in
      serum of dairy cows was determined and its applicability was demonstrated. In
      accordance with biological expectations from literature, rbST antibodies were
      induced in three out of four rbST-treated dairy cows. These rbST-induced
      antibodies were successfully detected for up to 4 weeks after the last rbST
      treatment, whereas no false positive results were obtained for 27 untreated dairy
      cows. This is the first method, able to overcome the interference of serum
      proteins and therefore, can be applied with high confidence for screening unknown
      herds of cattle for rbST antibodies, an important biomarker for pinpointing at
      rbST abuse in cattle.

PMID- 21964758
TI  - Lateral dielectrophoretic microseparators to measure the size distribution of
      blood cells.
AB  - Lateral displacement of blood cells occurred when they were passed over a planar
      interdigitated electrode array placed at an angle to the direction of flow, and
      was determined to be a function of cell size. A simplified line charge model was
      used to estimate numerically the lateral displacement. Based on the size-specific
      lateral displacement, a lateral dielectrophoretic (DEP) microseparator was
      developed to measure the size distribution of blood cells using fluorescence
      microscopy. To determine whether the lateral DEP microseparator was useful, it
      was used to detect acute leukemia by measuring the size distribution of blood
      cells. The lateral DEP microseparator provided a practical method for
      continuously and simultaneously separating multi-cell populations by size from a
      heterogeneous cell population. In the future, sensitivity of the lateral DEP
      microseparator could be improved and it could be automated by integrating
      subsequent advanced detection technologies in a micro-format.

PMID- 21964759
TI  - Serum levels and liver store of retinol and their association with night
      blindness in individuals with class III obesity.
AB  - BACKGROUND: Studies showed a rise in obesity prevalence in world population and
      evidences point to a possible association with vitamin A deficiency (VAD). The
      objective of this study is to assess vitamin A nutritional status through
      functional [night blindness diagnosis-xerophthalmia (XN)] and biochemical (serum
      levels and retinol liver store) indicators of class III obesity individuals and
      its association. METHODS: We studied 114 patients of both genders with BMI >=40
      kg/m2, candidates to bariatric surgery at Clinica Cirurgica Carlos Saboya in Rio
      de Janeiro, Brazil. XN was diagnosed through a standardized interview (WHO and
      MacLaren and Frigg), and serum levels and retinol liver store were quantified by
      HPLC-UV with <1.05 MUmol/L and < 20 mg/g cutoffs for VAD, respectively. RESULTS:
      XN prevalence was 23.8%, and serum levels and retinol liver store inadequacy were
      14.0% and 80%, respectively. The association between VAD and XN presence (p =
      0.003) was observed with the biochemical indicator and the gold standard, retinol
      liver store (p = 0.003 and p = 0.018, respectively). Means were 59.3%
      (sensitivity), 87.4% (specificity), and 80.8% (accuracy) as regards to the XN
      role in predicting VAD according to the biochemical indicator. As regards to
      retinol liver store, XN diagnosis presented 48% of sensitivity and 75% of
      specificity. VAD highest indexes occurred in patients with highest BMI (rs-0.21,
      p = 0.02). Distribution of XN prevalence was 59.2% according to serum retinol.
      CONCLUSIONS: VAD and XN prevalence was high in class III obesity individuals, and
      the functional indicator for XN diagnosis may be a promising method for diagnosis
      in this group.

PMID- 21964760
TI  - Relationship between dietary intake and microalbuminuria: findings from the
      Takahata study.
AB  - BACKGROUND: Although several studies have investigated the relationship between
      dietary nutrient intake and microalbuminuria, no study of an Asian population has
      been reported. The present study investigates the relationship between dietary
      intake and microalbuminuria in a general Japanese population. METHODS: We
      analyzed 675 men and 924 women who did not have diabetes. Participants who had a
      urinary albumin-to-creatinine ratio (UACR) >=300 mg/g, who did not complete a
      questionnaire regarding food frequency and who did not provide complete urine
      measurements were excluded. Nutrient intake was assessed by validated food
      frequency questionnaire. Microalbuminuria was defined as UACR >=30 mg/g. The
      relationship between dietary nutrient intake and microalbuminuria was examined
      using a multiple logistic regression model adjusted for age, total energy intake,
      body mass index, smoking status, systolic blood pressure and use of
      antihypertensive medication. RESULTS: No significant association was observed
      among the men. The multiple adjusted odds ratios (95% confidence interval) of
      having microalbuminuria per 1 standard deviation increase in total protein
      (%kcal), animal protein (%kcal), animal protein (g/day), animal fat, niacin,
      carbohydrate and beta-cryptoxanthin among the women were 1.33 (1.07-1.66), 1.35
      (1.09-1.66), 1.42 (1.08-1.88), 1.29 (1.05-1.59), 1.28 (1.04-1.57), 0.73 (0.58
      0.92) and 0.76 (0.59-0.996), respectively. The multiple adjusted odds ratio (95%
      confidence interval) of having microalbuminuria in the highest quintile of n-3
      polyunsaturated fatty acids compared with the lowest was 2.16 (1.03-4.54).
      CONCLUSION: Less animal protein and more beta-cryptoxanthin in the diet might
      help to prevent microalbuminuria. Prospective studies including controlled trials
      are required to confirm this conclusion.

PMID- 21964761
TI  - Automated peritoneal dialysis-related peritonitis due to Salmonella enteritidis
      in a pediatric patient.
AB  - Peritoneal dialysis (PD) represents the preferred renal replacement therapy in
      pediatric patients; however, the younger the age at PD initiation, the greater
      the risk of PD-related infections. We present here the first case report of a 14
      year-old girl with automated peritoneal dialysis-related Salmonella enteritidis
      peritonitis. The child responded only partially to an appropriate course of
      antibiotic therapy; the PD catheter was therefore removed and the patient shifted
      to hemodialysis. Along with the clinical course description, we review the
      mechanisms by which this group of Salmonella could infect the peritoneal cavity
      in patients on PD. Pediatric nephrologists should be aware that peritoneal
      catheter removal is often required for the complete resolution of this type of
      bacterial peritonitis.

PMID- 21964762
TI  - Gitelman syndrome: novel mutation and long-term follow-up.
AB  - We report a case of Gitelman syndrome presenting with fatigue, paresthesias,
      weakness of limbs and neck muscles since 2.5 years of age. Investigations showed
      hypokalemia and hypomagnesemia with urinary magnesium wasting. Genetic analysis
      revealed the presence of a novel homozygous mutation in the SLC12A3 gene
      (c.2879_2883+9ins14bp, p.Val 960 Glu fsx12). Management with potassium and
      magnesium supplements and spironolactone resulted in a significant improvement in
      symptoms. Over a follow-up of 11 years, the patient showed satisfactory growth
      and physical development.

PMID- 21964763
TI  - Disialogangliosides and TNFalpha alter gene expression for cytokines and
      chemokines in primary brain cell cultures.
AB  - Gangliosides have long been implicated in multiple pathologies affecting the
      central nervous system. Empirical studies have suggested the possibility that
      gangliosides, particularly GD3, work in tandem with pro-inflammatory cytokines,
      especially tumor necrosis factor alpha (TNFalpha), to initiate or facilitate cell
      death in the CNS. As a step toward unraveling the metabolic pathways activated in
      the pathogenesis of brain cell death, we have surveyed gene expression for a host
      of cytokines and chemokines in primary brain cell cultures exposed to GD3, GD1b,
      and TNFalpha for 24 h. An initial screen of 98 genes on a focused mini-array
      revealed the expression of at least 28 genes related to cell growth, death, or
      inflammation in our system of mixed cells cultured from neonatal rat brains.
      Clear evidence of a differential response to the gangliosides or TNFalpha was
      seen in 12 genes. Quantitative PCR was used to validate the response of six of
      these genes. We found that both GD3 and GD1b, but not TNFalpha, up-regulated
      expression of macrophage inflammatory protein 3 (MIP3A) and interleukin-1
      receptor 1 (IL1R1), but down-regulated fibroblast growth factor 13 (FGF13). The
      expression of FGF receptor activating protein 1 (FRAG1) and interleukin-3
      receptor alpha (IL3RA) was down-regulated by GD3. Exposure to TNFalpha resulted
      in a dramatic up-regulation of IL3RA and chemokine ligand 2 (CCL2), both of which
      have been implicated in multiple sclerosis. Our results provide strong evidence
      that the expression of these genes might be critical links in the metabolic
      cascades leading to cell degeneration and death in the brain.

PMID- 21964764
TI  - Effects of antagonists and heat on TRPM8 channel currents in dorsal root ganglion
      neuron activated by nociceptive cold stress and menthol.
AB  - Transient receptor potential ion channel melastatin subtype 8 (TRPM8) is
      activated by cold temperature and cooling agents, such as menthol and icilin.
      Compounds containing peppermint are reported to reduce symptoms of environmental
      cold stress such as cold allodynia in dorsal root ganglion (DRG) neuron; however,
      the underlying mechanisms of action are unclear. We tested the effects of
      physiological heat (37 degrees C), anthralic acid (ACA and 0.025 mM), 2
      aminoethyl diphenylborinate (2-APB and 0.05) on noxious cold (10 degrees C) and
      menthol (0.1 mM)-induced TRPM8 cation channel currents in the DRG neurons of
      rats. DRG neurons were freshly isolated from rats. In whole-cell patch clamp
      experiments, TRPM8 currents were consistently induced by noxious cold or menthol.
      TRPM8 channels current densities of the neurons were higher in cold and menthol
      groups than in control. When the physiological heat is introduced by chamber
      TRPM8 channel currents were inhibited by the heat. Noxious cold-induced Ca(2+)
      gates were blocked by the ACA although menthol-induced TRPM8 currents were not
      blocked by ACA and 2-APB. In conclusion, the results suggested that activation of
      TRPM8 either by menthol or nociceptive cold can activate TRPM8 channels although
      we observed the protective role of heat, ACA and 2-APB through a TRPM8 channel in
      nociceptive cold-activated DRG neurons. Since cold allodynia is a common feature
      of neuropathic pain and diseases of sensory neuron, our findings are relevant to
      the etiology of neuropathology in DRG neurons.

PMID- 21964765
TI  - Altered biochemical parameters in saliva of pediatric attention deficit
      hyperactivity disorder.
AB  - Oxidative stress is one of the common causes in etiopathogenesis of attention
      deficit hyperactivity disorder (ADHD). Hence, the salivary levels of protein
      thiols, ceruloplasmin, magnesium and pseudocholinesterase were estimated in
      children with ADHD. The symptoms of ADHD were identified using Conner's rating
      and DSM IV criteria. Saliva was collected and assessed for the levels of protein
      thiols, ceruloplasmin, magnesium and pseudocholinesterase,
      spectrophotometrically. It was also checked for pH and the flow rate was noted
      down. There was a significant increase (P < 0.001) in the salivary protein thiols
      and pseudocholinesterase levels in ADHD children when compared to controls.
      Ceruloplasmin levels did not show any significant change. Magnesium levels were
      significantly decreased (P < 0.001) in cases when compared to controls. Further,
      a receiver operating characteristic curve for validity of the biochemical
      parameters in saliva of ADHD children indicated a sensitivity and specificity
      above 90% for protein thiols and magnesium values. Our study shows that protein
      thiols, magnesium, and pseudocholinesterase might have a role in the pathogenesis
      of ADHD and saliva can be effectively used as a non-invasive tool for evaluation
      of such children.

PMID- 21964766
TI  - Regression of melanoma metastases after immunotherapy is associated with
      activation of antigen presentation and interferon-mediated rejection genes.
AB  - We present the results of a comparative gene expression analysis of 15 metastases
      (10 regressing and 5 progressing) obtained from 2 melanoma patients with mixed
      response following different forms of immunotherapy. Whole genome transcriptional
      analysis clearly indicate that regression of melanoma metastases is due to an
      acute immune rejection mediated by the upregulation of genes involved in antigen
      presentation and interferon mediated response (STAT-1/IRF-1) in all the
      regressing metastases from both patients. In contrast, progressing metastases
      showed low transcription levels of genes involved in these pathways. Histological
      analysis showed T cells and HLA-DR positive infiltrating cells in the regressing
      but not in the progressing metastases. Quantitative expression analysis of HLA
      A,B and C genes on microdisected tumoral regions indicate higher HLA expression
      in regressing than in progressing metastases. The molecular signature obtained in
      melanoma rejection appeared to be similar to that observed in other forms of
      immune-mediated tissue-specific rejection such as allograft, pathogen clearance,
      graft versus host or autoimmune disease, supporting the immunological constant of
      rejection. We favor the idea that the major factor determining the success or
      failure of immunotherapy is the nature of HLA Class I alterations in tumor cells
      and not the type of immunotherapy used. If the molecular alteration is reversible
      by the immunotherapy, the HLA expression will be upregulated and the lesion will
      be recognized and rejected. In contrast, if the defect is structural the MHC
      Class I expression will remain unchanged and the lesion will progress.

PMID- 21964767
TI  - Bi-spectral index, entropy and predicted plasma propofol concentrations with
      target controlled infusions in Indian patients.
AB  - OBJECTIVE: Many processed electroencephalographic signals are used now to help
      the anaesthesiologist titrate the depth of sedation. We investigated the
      relationship between target plasma propofol concentration and objective end
      points of sedation- Bispectral Index (BIS), State Entropy (SE) and Response
      Entropy (RE)-at clinical end-points as assessed by Modified Observer Assessment
      of Alertness/sedation Scale (MOAAS) in Indian patients. METHODS: Eighteen ASA 1
      and 2 Indian adult patients scheduled to undergo elective surgery were included.
      The target control infusion (TCI) of propofol was administered using
      'Diprifusor'. The level of sedation was assessed using MOAAS by the
      anaesthesiologist. BIS, SE, RE were recorded throughout. TCI was started at 0.5
      MUg/ml and increased by 0.5 MUg/ml every 6 min till MOAAS scores reached 0 or
      there was sustained BIS value less than 30. RESULTS: The EC(50) and EC(95) of
      predicted plasma propofol concentration for loss of consciousness (assessed by
      loss of response to verbal command), were 2.3 and 2.8 MUg/ml respectively and for
      loss of response to painful stimuli (trapezius squeeze) were 4.0 and 5.0 MUg/ml
      respectively. The BIS and entropy values (EC(50) and EC(95)) for loss of
      consciousness and response to painful stimuli in Indian patients were estimated.
      The preliminary relation of target plasma propofol concentration with BIS was
      found to be BIS = 100.5-16.4 * (Target concentration). CONCLUSIONS: The target
      plasma propofol concentrations required to produce unconsciousness and loss of
      response to painful stimuli in Indian patients have been estimated. Also, the
      relations between target plasma concentration and objective measures of different
      levels of anaesthesia have been established.

PMID- 21964769
TI  - The Akt/FoxO1/p27 pathway mediates the proliferative action of liraglutide in
      beta cells.
AB  - Numerous studies have shown that liraglutide, a modified form of human glucagon
      like peptide-1 (GLP-1), increases beta-cell mass. However, the underlying
      molecular mechanisms remain unclear. In the present study, we investigated the
      role of Akt/FoxO1/p27 signaling in liraglutide-induced beta-cell proliferation.
      INS-1 rat insulinoma cells were exposed to two different concentrations of
      liraglutide. MTT assay was performed to evaluate beta-cell proliferation. The
      expression of Akt/FoxO1/p27 was detected by quantitative real-time PCR and
      Western blotting. The results revealed that in comparison to the non-treatment
      group, stimulating INS-1 cells with 10 and 100 nM liraglutide caused beta-cell
      proliferation to be significantly enhanced. The mRNA levels of p27 in INS-1 cells
      declined upon treatment with liraglutide compared to the non-treatment group.
      Western blot analysis revealed that the phosphorylation of Akt and FoxO1 was
      markedly elevated following exposure to liraglutide. Moreover, LY294002, a
      phosphatidylinositol 3-kinase (PI-3K) inhibitor, significantly abrogated
      liraglutide-induced effects. Therefore, we conclude that liraglutide increased
      the beta-cell mass by upregulating beta-cell proliferation and that the
      proliferative action of liraglutide in beta cells was mediated by activation of
      PI-3K/Akt, which resulted in inactivation of FoxO1 and decreased p27.

PMID- 21964770
TI  - Impact of partial volume effects on visceral adipose tissue quantification using
      MRI.
AB  - PURPOSE: To quantitatively estimate the impact of partial volume effects on
      visceral adipose tissue (VAT) quantification using typical resolution magnetic
      resonance imaging (MRI). MATERIALS AND METHODS: Nine normal or overweight
      subjects were scanned at central abdomen levels with a water-saturated, balanced
      steady-state free precession (b-SSFP) sequence. The water-saturation
      effectiveness was evaluated with region-of-interest analysis on fat, muscle,
      bowel, and noise areas. The number of full-volume (FV) and partial-volume (PV)
      fat pixels was estimated based on a gray-level histogram model of water-saturated
      images. Both FV and PV fat amounts were quantified. RESULTS: High-quality, fat
      only images were generated with the b-SSFP imaging method. Fat SNR was 77.7 +/-
      25.6 and water-saturation was effective, with the average fat-to-water signal
      intensity ratio = 20.7 +/- 3.8. The average ratio of partial- to full-volume fat
      amounts was 104.0%. The ratio was higher with lower body mass index (BMI) and PV
      fat amount only increased slightly when BMI increased. CONCLUSION: PV fat
      contributes a significant amount of fat to fat measurements on typical spatial
      resolution MRI on normal and overweight subjects. The relative PV fat
      contribution is markedly higher in slimmer patients. Inclusion of this portion of
      the adipose tissue will increase overall accuracy and decrease variability of VAT
      quantification using MRI.

PMID- 21964768
TI  - Proficiency in the diagnosis of nonpolypoid colorectal neoplasm yields high
      adenoma detection rates.
AB  - BACKGROUND AND AIMS: Current efforts to prevent colorectal cancer focus on the
      detection and removal of neoplasms. Nonpolypoid colorectal neoplasms (NP-CRN)
      have a subtle appearance that can be difficult to recognize during colonoscopy.
      Endoscopists must first be familiar with the patterns of NP-CRN in order to
      detect and diagnose them. We studied the adenoma detection rates of endoscopists
      who had trained to detect NP-CRN, versus endoscopists who had not. MATERIALS AND
      METHODS:  DESIGN: Retrospective Nested Case Control Study. SETTING: Outpatient
      Screening Colonoscopy. PARTICIPANTS: Adult Veterans. INTERVENTION: Proficiency in
      the features and diagnosis of NP-CRN. MAIN OUTCOMES MEASUREMENTS: Adenoma
      detection. RESULTS: In total, 462 patients had screening colonoscopies-267 by
      colonoscopists who had trained in the features and diagnosis of NP-CRN. Patient
      characteristics were similar between groups-the majority were men with a mean age
      of 62 +/- 6 years. Neoplasia was more prevalent (45.7 vs. 34.9%; p = 0.02) in
      patients evaluated by the trained compared to the conventionally trained group.
      Trained colonoscopists had a higher adenoma detection rate (0.76 vs. 0.54
      adenomas per patient, p < 0.001); removed a higher proportion of neoplasia (77
      vs. 35%, p < 0.001); and more frequently diagnosed NP-CRN lesions (OR 2.98, 95%
      CI: 1.46-6.08) compared to colonoscopists without supplemental training.
      CONCLUSIONS: Endoscopists who are proficient in the detection of NP-CRN had
      significantly higher adenoma detection rates-of both polypoid and flat adenomas
      compared to endoscopists without training, and were more specific in resection of
      adenomatous over hyperplastic lesions.

PMID- 21964771
TI  - Correlation of intercentromeric distance, mosaicism, and sexual phenotype:
      molecular localization of breakpoints in isodicentric Y chromosomes.
AB  - Isodicentric chromosomes are among the structural abnormalities of the Y
      chromosome that are commonly identified in patients. The simultaneous 45,X cell
      line that is generated in cell division due to instability of the isodicentric Y
      chromosome [idic(Y)] has long been hypothesized to explain the variable sexual
      development of these patients, although gonads have been studied in only a subset
      of cases. We report here on the molecular localization of breakpoints in ten
      patients with an idic(Y). Breakpoints were mapped by FISH using BACs; gonads and
      fibroblasts were also analyzed when possible to evaluate the level of mosaicism.
      First, we demonstrate great tissue variability in the distribution of idic(Y).
      Second, palindromes and direct repeats were near the breakpoint of several
      idic(Y), suggesting that these sequences play a role in the formation of idic(Y).
      Finally, our data suggest that intercentromeric distance has a negative influence
      on the stability of idic(Y), as a greater proportion of cells with breakage or
      loss of the idic(Y) were found in idic(Y) with a greater intercentromeric
      distance. Females had a significantly greater intercentromeric distance on their
      idic(Y) than did males. In conclusion, our study indicates that the Y chromosome
      contains sequences that are more prone to formation of isodicentric chromosomes.
      We also demonstrate that patients with an intercentromeric distance greater than
      20 Mb on their idic(Y) are at increased risk of having a female sexual phenotype.

PMID- 21964772
TI  - "Dilute-and-shoot" triple parallel mass spectrometry method for analysis of
      vitamin D and triacylglycerols in dietary supplements.
AB  - A method is demonstrated for analysis of vitamin D fortified dietary supplements
      that eliminates virtually all chemical pretreatment prior to analysis, which is
      referred to as a "dilute-and-shoot" method. Three mass spectrometers, in
      parallel, plus a UV detector, an evaporative light-scattering detector (ELSD),
      and a corona charged aerosol detector (CAD) were used to allow a comparison of
      six detectors simultaneously. Ultraviolet data were analyzed using internal
      standard, external standard, and response factor approaches. The contents of
      gelcaps that contained 2,000 IU (50 MUg) vitamin D(3) in rice bran oil, diluted
      to 100 mL, were analyzed without the need for lengthy saponification and
      extraction. Vitamin D(3) was analyzed using UV detection, extracted ion
      chromatograms, selected ion monitoring (SIM) atmospheric pressure chemical
      ionization mass spectrometry (APCI-MS), and two transitions of multiple reaction
      monitoring (MRM) APCI-MS. The internal standard, external standard, and response
      factor methods gave values of 0.5870 +/- 0.0045, 0.5893 +/- 0.0041, and 0.5889 +/
      0.0045 MUg/mL, respectively, by UV detection. The values obtained by MS were
      0.6117 +/- 0.0140, 0.6018 +/- 0.0244, and 0.5848 +/- 0.0146 MUg/mL by SIM and two
      transitions of MRM, respectively. The triacylglycerols in the oils were analyzed
      using full-scan APCI-MS, electrospray ionization (ESI) MS, up to MS(4), an ELSD,
      and a CAD. The method proved to be very sensitive for vitamin D(3), as well as
      triacylglycerols (TAGs), allowing identification of intact TAGs containing fatty
      acids up to 28 carbons in length. LC-ESI-MS of glycerin polymers is also
      demonstrated.

PMID- 21964773
TI  - Hyphenation of a carbon analyzer to photo-ionization mass spectrometry to unravel
      the organic composition of particulate matter on a molecular level.
AB  - The carbonaceous fraction of airborne particulate matter (PM) is of increasing
      interest due to the adverse health effects they are linked to. Its analytical
      ascertainment on a molecular level is still challenging. Hence, analysis of
      carbonaceous fractions is often carried out by determining bulk parameters such
      as the overall content of organic compounds (OC) and elemental carbon (EC) as
      well as the total carbon content, TC (sum of OC and EC), however, no information
      about the individual substances or substance classes, of which the single
      fractions consist can be obtained. In this work, a carbon analyzer and a photo
      ionization time-of-flight mass spectrometer (PI-TOF-MS) were hyphenated to
      investigate individual compounds especially from the OC fractions. The carbon
      analyzer enables the stepwise heating of particle samples and provides the bulk
      parameters. With the PI-TOF-MS, it is possible to detect the organic compounds
      released during the single-temperature steps due to soft ionization and fast
      detection of the molecular ions. The hyphenation was designed, built up,
      characterized by standard substances, and applied to several kinds of samples,
      such as ambient aerosol, gasoline, and diesel emission as well as wood combustion
      emission samples. The ambient filter sample showed a strong impact of wood
      combustion markers. This was revealed by comparison to the product pattern of the
      similar analysis of pure cellulose and lignin and the wood combustion PM. At
      higher temperatures (450  degrees C), a shift to smaller molecules occurred due
      to the thermal decomposition of larger structures of oligomeric or polymeric
      nature comparable to lignocelluloses and similar oxygenated humic-like
      substances. Finally, particulate matter from gasoline and diesel containing 10%
      biodiesel vehicle exhaust has been analyzed. Gasoline-derived PM exhibited large
      polycyclic aromatic hydrocarbons, whereas diesel PM showed a much higher total
      organic content. The detected pattern revealed a strong influence of the
      biodiesel content on the nature of the particulate organic material.

PMID- 21964774
TI  - Critical thresholds for cerebrovascular reactivity after traumatic brain injury.
AB  - INTRODUCTION: Pressure-reactivity index (PRx) is a useful tool in brain
      monitoring of trauma patients, but the question remains about its critical
      values. Using our TBI database, we identified the thresholds for PRx and other
      monitored parameters that maximize the statistical difference between
      death/survival and favorable/unfavorable outcomes. We also investigated how these
      thresholds depend on clinical factors such as age, gender and initial GCS.
      METHODS: A total of 459 patients from our database were eligible. Tables of 2 * 2
      format were created grouping patients according to survival/death or
      favorable/unfavorable outcomes and varying thresholds for PRx, ICP and CPP.
      Pearson's chi square was calculated, and the thresholds returning the highest
      score were assumed to have the best discriminative value. The same procedure was
      repeated after division according to clinical factors. RESULTS: In all patients,
      we found that PRx had different thresholds for survival (0.25) and for favorable
      outcome (0.05). Thresholds of 70 mmHg for CPP and 22 mmHg for ICP were identified
      for both survival and favorable outcomes. The ICP threshold for favorable outcome
      was lower (18 mmHg) in females and patients older than 55 years. In logistic
      regression models, independent variables associating with mortality and
      unfavorable outcome were age, GCS, ICP and PRx. CONCLUSION: The prognostic role
      of PRx is confirmed but with a lower threshold of 0.05 for favorable outcome than
      for survival (0.25). Results for ICP are in line with current guidelines.
      However, the lower value in elderly and in females suggests increased
      vulnerability to intracranial hypertension in these groups.

PMID- 21964775
TI  - Asymmetric posterior reversible encephalopathy syndrome complicating hemodynamic
      augmentation for subarachnoid hemorrhage-associated cerebral vasospasm.
AB  - BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a rare
      complication of hemodynamic augmentation for subarachnoid hemorrhage (SAH)
      associated vasospasm. The roles of hyperperfusion and hypoperfusion in the
      genesis of PRES remain uncertain. METHODS: Case report. RESULTS: We admitted a 35
      year-old woman with Hunt & Hess grade II SAH secondary to rupture of a right
      middle cerebral artery (MCA) aneurysm. This was surgically clipped. Beginning on
      hospital day 3, she developed recurrent symptomatic vasospasm of the right MCA
      despite hemodynamic augmentation to a MAP as high as 130 mmHg and endovascular
      therapy. On hospital day 7, after 36 h of sustained MAP 120-130 mmHg, her level
      of arousal progressively declined, culminating in stupor and two generalized
      tonic-clonic seizures. MRI showed widespread, yet markedly asymmetric changes
      consistent with PRES largely sparing the right MCA territory. After the MAP was
      decreased to 85-100 mmHg, she had no further seizures. 2 days later she was fully
      alert with mild left hemiparesis. CONCLUSIONS: PRES is a rare complication of
      hemodynamic augmentation that should be considered in the differential diagnosis
      of delayed neurological decline in patients with aneurysmal SAH-associated
      cerebral vasospasm. The markedly asymmetric distribution of PRES lesions with
      sparing of the territory affected by vasospasm supports the hypothesis that
      hyperperfusion underlies the pathophysiology of this disorder.

PMID- 21964776
TI  - Droplet formation via flow-through microdevices in Raman and surface enhanced
      Raman spectroscopy--concepts and applications.
AB  - This review outlines concepts and applications of droplet formation via flow
      through microdevices in Raman and surface enhanced Raman spectroscopy (SERS) as
      well as the advantages of the approach. Even though the droplet-based flow
      through technique is utilized in various fields, the review focuses on
      implementing droplet-based fluidic systems in Raman and SERS as these highly
      specific detection methods are of major interest in the field of analytics. With
      the combination of Raman or SERS with droplet-based fluidics, it is expected to
      achieve novel opportunities for analytics. Besides the approach of using droplet
      based microfluidic devices as a detection platform, the unique properties of flow
      through systems for the formation of droplets are capitalized to produce SERS
      active substrates and to accomplish uniform sample preparation. Within this
      contribution, previous reported applications on droplet-based flow-through Raman
      and SERS approaches and the additional benefit with regard to the importance in
      the field of analytics are considered.

PMID- 21964777
TI  - Application of an enantioselective LC-ESI MS/MS procedure to determine R- and S
      hyoscyamine following intravenous atropine administration in swine.
AB  - S-hyoscyamine (S-hyo) is a natural plant tropane alkaloid acting as a muscarinic
      receptor (MR) antagonist. Its racemic mixture (atropine) is clinically used in
      pre-anaesthesia, ophthalmology and for the antidotal treatment of
      organophosphorus (OP) poisoning with nerve agents or pesticides even though R-hyo
      exhibits no effects on MR. Further investigative research is required to optimize
      treatment of OP poisoning. Swine are often the animal model utilized due to
      similarities in physiology and antidote response to humans. However, no studies
      have been reported that elucidated differences in the kinetics of R- and S-hyo.
      Therefore, the concentration-time profiles of total hyo as well as both
      enantiomers were analyzed in plasma after intravenous administration of atropine
      sulfate (Atr(2) SO(4) , 100 ug/kg) to anaesthetized swine. For quantification
      plasma samples were incubated separately with human serum (procedure A) and
      rabbit serum (procedure B). The rabbit serum used contained atropinesterase,
      which is suitable for stereoselective hydrolysis of S-hyo, while human serum does
      not hydrolyze either enantiomer. After incubation samples were precipitated and
      the supernatant was analyzed by RP-HPLC-ESI MS/MS. Procedure A allowed
      determination of total hyo and procedure B remaining R-hyo concentrations. S-hyo
      was calculated as the difference of the two procedures. Concentration data were
      regressed by a two-phase decay according to a two-compartment open model
      revealing similar kinetics for both enantiomers thus indicating distribution,
      metabolism and elimination without obvious stereoselective preference in tested
      swine.

PMID- 21964778
TI  - Overview of chemical genomics and proteomics.
AB  - Chemical genetics, genomics, and proteomics have been in existence as distinct
      offshoots of chemical biology for about 20 years. This review provides a brief
      definition of each, followed by some examples of how each technology is being
      used to advance basic research and drug discovery.

PMID- 21964779
TI  - Exploring chemical space: recent advances in chemistry.
AB  - Recent advances and concepts for exploring chemical space are highlighted in this
      chapter and show how the synthetic chemical world meets the demand of making
      large and relevant collection of new molecules for analyzing the biological world
      more closely.

PMID- 21964780
TI  - In silico design of small molecules.
AB  - Computational methods now play an integral role in modern drug discovery, and
      include the design and management of small molecule libraries, initial hit
      identification through virtual screening, optimization of the affinity and
      selectivity of hits, and improving the physicochemical properties of the lead
      compounds. In this chapter, we survey the most important data sources for the
      discovery of new molecular entities, and discuss the key considerations and
      guidelines for virtual chemical library design.

PMID- 21964781
TI  - Surface plasmon resonance for proteomics.
AB  - Surface plasmon resonance (SPR) is a well-established label-free technique to
      detect mass changes near an SPR surface. For 20 years the benefits of SPR have
      been proven in biomolecular interaction analysis, including measurements of
      affinity and kinetics. The emergence of proteomics and a need for high throughput
      analysis drives the development of SPR systems capable of analyzing microarrays.
      The use of SPR imaging (also known as SPR microscopy) makes it possible to use
      multiplexed arrays to follow binding reactions. As SPR only analyzes the binding
      process, but not the identity of captured molecules on the SPR surface,
      technologies have been developed to integrate SPR with mass spectrometric (MS)
      analysis. Such approaches involve the recovery of analytes from the SPR surface
      and subsequent MALDI-TOF MS analysis, or LC-MS/MS after tryptic digestion of
      recovered proteins. An approach compatible with SPR arrays is on-chip MALDI-TOF
      MS, from arrayed spots on an SPR surface. This review describes some exciting
      developments in the application of SPR to proteomics, using instruments which are
      on the market already, or are expected to be available in the years to come.

PMID- 21964782
TI  - Biomimetic affinity ligands for immunoglobulins based on the multicomponent Ugi
      reaction.
AB  - Affinity chromatography is the method of choice for biomolecule separation and
      isolation with highly specific target recognition; it is ideally suited to the
      purification of immunotherapeutic proteins (i.e., mAbs). Conventional affinity
      purification protocols are based on natural immunoglobulin (Ig)-binding proteins,
      which are expensive to produce, labile, unstable, and exhibit lot-to-lot
      variability. Biological ligands are now being replaced by cost-effective,
      synthetic ligands, derived from the concepts of rational design and combinatorial
      chemistry, aided by in silico approaches. In this chapter, we describe a new
      synthetic procedure for the development of affinity ligands for immunoglobulins
      based on the multicomponent Ugi reaction. The lead ligand developed herein is
      specific for the IgG-Fab fragment and mimics Protein L (PpL), an IgG-binding
      protein isolated from Peptostreptococcus magnus strains and usually used for the
      purification of antibodies and their fragments.

PMID- 21964783
TI  - Preparation of photo-cross-linked small molecule affinity matrices for affinity
      selection of protein targets for biologically active small molecules.
AB  - Small molecule-immobilized affinity matrices are indispensable tools in chemical
      genomics to screen and purify protein targets for biologically active small
      molecules. Usually, prior to immobilization, small -molecules have to be
      derivatized at a position that does not significantly abrogate the intrinsic
      biological activity, or chemically synthesized to have an appropriate functional
      group for the immobilization chemistry. Here, we describe a photo-cross-linking
      technique to immobilize biologically active small molecules for protein target
      screening, without the need for chemical derivatization.

PMID- 21964784
TI  - Profiling cellular myristoylation and palmitoylation using omega-alkynyl fatty
      acids.
AB  - Methods to detect and characterize cellular protein myristoylation and
      palmitoylation are invaluable in cell biology, immunology, and virology.
      Recently, we developed omega-alkynyl fatty acid probes for monitoring
      myristoylation and palmitoylation of cellular proteins. This article describes a
      biochemical procedure for metabolic labeling of cells with omega-alkynyl fatty
      acids and click chemistry.

PMID- 21964785
TI  - Fluorescence labels in kinases: a high-throughput kinase binding assay for the
      identification of DFG-out binding ligands.
AB  - Despite the hundreds of kinase inhibitors currently in discovery and pre-clinical
      phases, the number of kinase inhibitors which have been approved and are on the
      market remains low by comparison. This discrepancy reflects the challenges which
      accompany the development of kinase inhibitors which are relatively specific and
      less toxic. Targeting protein kinases with ATP-competitive inhibitors has been
      the classical approach to inhibiting kinase activity, but the highly conserved
      nature of the ATP-binding site contributes to poor inhibitor selectivity, issues
      which have particularly hampered the development of novel kinase inhibitors. We
      developed a high-throughput screening technology that can discriminate for
      inhibitors which stabilize the inactive "DFG-out" kinase conformation by binding
      within an allosteric pocket adjacent to the ATP-binding site. Here, we describe
      how to use this approach to measure the K (d) of ligands, as well as how to
      kinetically characterize the binding and dissociation of ligands to the kinase.
      We also describe how this technology can be used to rapidly screen small molecule
      libraries at high throughput.

PMID- 21964786
TI  - Electrochemical aptamer sensor for small molecule assays.
AB  - Detection and quantification of small molecules have played essential roles in
      environmental analysis and clinical diagnosis. Aptamers are oligonucleic acids
      that bind to a specific target molecule with high specificity and affinity which
      are promising features for sensing small molecules. Electrochemical detection is
      an attractive way to exploit aptamer sensors (aptasensors) because of its high
      sensitivity, simple instrumentation, low cost, fast response and portability.
      Herein, we describe a label-free small molecular aptasensor based on a signal
      amplification mechanism which uses gold nanoparticles. This aptasensor can
      selectively detect low nanomolar levels of ATP, the example target compound.

PMID- 21964787
TI  - Miniaturized, microarray-based assays for chemical proteomic studies of protein
      function.
AB  - Systematic analysis of protein and enzyme function typically requires scale-up of
      protein expression and purification prior to assay development; this can often be
      limiting. Miniaturization of assays provides an alternative approach, but simple,
      generic methods are in short supply. Here we show how custom microarrays can be
      adapted to this purpose. We discuss the different routes to array fabrication and
      describe in detail one facile approach in which the purification and
      immobilization procedures are combined into a single step, significantly
      simplifying the array fabrication process. We illustrate this approach by
      reference to the creation of arrays of human protein kinases and of human
      cytochrome P450s. We discuss methods for both ligand-binding and turnover-based
      assays, as well as data analysis on such arrays.

PMID- 21964788
TI  - Glycan microarrays.
AB  - Glycan microarrays are presentations of multiple glycans or glycoconjugates
      printed on a single slide for screening with glycan-binding proteins (GBPs),
      which include lectins, antibodies, bacteria, and viruses. Glycans derivatized
      with functional groups can be immobilized onto appropriately activated glass
      slides to generate glycan microarrays where each glycan is printed at similar
      concentrations. Here we describe a method for fluorescently and functionally
      derivatizing free reducing glycans, printing microarrays, and interrogating the
      microarrays with GBPs.

PMID- 21964789
TI  - Resolving bottlenecks for recombinant protein expression in E. coli.
AB  - Escherichia coli is widely used as an expression system for production of
      recombinant proteins of prokaryotic and eukaryotic origin. A large body of
      knowledge has accumulated throughout the last few decades regarding expression of
      recombinant proteins in E. coli. However, despite this progress, protein
      production, primarily of eukaryotic origin, still remains a challenge. The
      biggest obstacle lies in obtaining large amounts of a given protein in a
      correctly folded form. Several strategies are being used to increase both yield
      and solubility. These include expression as fusion proteins, co-expression with
      molecular chaperones, or with a protein partner(s), and the use of multiple
      constructs for each protein. In this chapter, we focus on strategies for creating
      expression vectors, as well as on guidelines for improving recombinant protein
      solubility.

PMID- 21964790
TI  - Recombinant protein expression in the baculovirus-infected insect cell system.
AB  - Over the last two decades, the use of eukaryotic cells for expression of
      recombinant proteins has become the preferred choice for many applications. This
      is primarily the case when posttranslational modifications and correct disulfide
      bond formation are necessary for protein folding and activity. Among the
      eukaryotic expression systems, the baculovirus-infected insect cell platform has
      gained particular attention, resulting in the development and implementation of
      multiple strategies for protein expression. Here, we present baculovirus-infected
      insect cells as an efficient expression system for eukaryotic proteins. We
      demonstrate a simplified and a shortened procedure for recombinant virus
      production that is sufficient for large-scale production of proteins in insect
      cells.

PMID- 21964791
TI  - Systems for the cell-free synthesis of proteins.
AB  - We describe a system for the cell-free expression of proteins based on extracts
      from Escherichia coli. Two reaction configurations, batch and continuous
      exchange, are discussed and analytical scale as well as preparative scale setups
      are documented. Guidelines for the systematic development and optimization of
      cell-free expression protocols are given in detail. We further provide specific
      protocols and parameters for the cell-free production of membrane proteins. High
      throughput screening applications of CF expression systems are exemplified as new
      tools for genomics and proteomics studies.

PMID- 21964792
TI  - Protein identification by MALDI-TOF mass spectrometry.
AB  - MALDI-TOF mass spectrometers are now commonplace and their relative ease of use
      means that most non-specialist labs can readily access the technology for the
      rapid and sensitive analysis of biomolecules. One of the main uses of MALDI-TOF
      MS is in the identification of proteins, by peptide mass fingerprinting (PMF).
      Here we describe a simple protocol that can be performed in a standard
      biochemistry laboratory, whereby proteins separated by 1D or 2D gel
      electrophoresis can be identified at femtomole levels. The procedure involves
      excision of the spot or band from the gel, washing and destaining, reduction and
      alkylation, in-gel trypsin digestion, MALDI-TOF-MS of the tryptic peptides and
      database searching of the PMF data. Up to 96 protein samples can easily be
      manually processed at one time by this method.

PMID- 21964793
TI  - The role of satisfaction and emotional response in the choice mechanisms of
      suburban natural-areas users.
AB  - The unique observations and experiences of users of suburban natural areas lead
      them to perceive their surroundings in a manner associated with their personal
      values. It follows that every individual has a unique cognitive decision-making
      structure. This paper examines users' affective and cognitive evaluation of a
      particular suburban natural area by applying the means-end chain method to reveal
      the cognitive mechanism by which users link the attributes and benefits of an
      environmental public good with their own personal values. Analysis of a survey
      conducted of visitors to a Spanish suburban natural area (park) reveals the main
      attributes to be the opportunity to practice sports and proximity of the park and
      the main potential benefits to be the improvement of physical and psychological
      well-being. The desired personal values include fun, quality of life and self
      fulfillment at the individual level and improved social relationships at the
      collective level. The paper also tests for cross-group, cognitive-structure
      differences in visitor groups, segmented by level of satisfaction and reported
      range of emotions, and finds that perceived physical and psychological health
      improvements and individual and social awareness increase with higher levels of
      satisfaction and emotional response. Therefore, the recommendations for natural
      area management suggested by these findings include enhancing the scenic beauty
      and peacefulness of suburban natural areas in order to improve the affective
      state of visitors because this could contribute to reducing social costs
      (including health care) within the area of influence of the natural area.

PMID- 21964794
TI  - Neuron-specific stimulus masking reveals interference in spike timing at the
      cortical level.
AB  - The auditory system is capable of robust recognition of sounds in the presence of
      competing maskers (e.g., other voices or background music). This capability
      arises despite the fact that masking stimuli can disrupt neural responses at the
      cortical level. Since the origins of such interference effects remain unknown, in
      this study, we work to identify and quantify neural interference effects that
      originate due to masking occurring within and outside receptive fields of
      neurons. We record from single and multi-unit auditory sites from field L, the
      auditory cortex homologue in zebra finches. We use a novel method called spike
      timing-based stimulus filtering that uses the measured response of each neuron to
      create an individualized stimulus set. In contrast to previous adaptive
      experimental approaches, which have typically focused on the average firing rate,
      this method uses the complete pattern of neural responses, including spike timing
      information, in the calculation of the receptive field. When we generate and
      present novel stimuli for each neuron that mask the regions within the receptive
      field, we find that the time-varying information in the neural responses is
      disrupted, degrading neural discrimination performance and decreasing spike
      timing reliability and sparseness. We also find that, while removing stimulus
      energy from frequency regions outside the receptive field does not significantly
      affect neural responses for many sites, adding a masker in these frequency
      regions can nonetheless have a significant impact on neural responses and
      discriminability without a significant change in the average firing rate. These
      findings suggest that maskers can interfere with neural responses by disrupting
      stimulus timing information with power either within or outside the receptive
      fields of neurons.

PMID- 21964795
TI  - Liver upregulation of genes involved in cortisol production and action is
      associated with metabolic syndrome in morbidly obese patients.
AB  - BACKGROUND: Hepatic 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1)
      activity, which converts cortisone (inactive) to cortisol, is downregulated in
      obesity. However, this compensation fails in obese with metabolic abnormalities,
      such as diabetes. To further characterize the tissue-specific cortisol
      regeneration in obesity, we have investigated the mRNA expression of genes
      related to local cortisol production, i.e., 11beta-HSD1, hexose-6-phosphate
      dehydrogenase (H6PDH) and cortisol action, glucocorticoid receptor (GR) and a
      cortisol target gene, phosphoenolpyruvate carboxykinase (PEPCK) in the liver, and
      visceral (VAT) and subcutaneous (SAT) adipose tissues from morbidly obese
      patients with and without metabolic syndrome (MS). METHODS: Fifty morbidly obese
      patients undergoing bariatric surgery, 14 men (mean age, 41.3 +/- 3.5 years; BMI,
      48.0 +/- 3.6 kg/m(2)) and 36 women (mean age, 44.6 +/- 1.9 years; BMI, 44.9 +/-
      1.2 kg/m(2)), were classified as having MS (MS+, n = 20) or not (MS-, n = 30).
      Tissue mRNA levels were measured by real-time polymerase chain reaction. RESULTS:
      Hepatic mRNA levels of these genes were higher in obese patients with MS (11beta
      HSD1, P = 0.002; H6PDH, P = 0.043; GR, P = 0.033; PEPCK, P = 0.032) and
      positively correlated with the number of clinical characteristics that define the
      MS. The expression of the four genes positively correlated among them. In
      contrast to the liver, these genes were not differently expressed in VAT or SAT,
      when MS+ and MS- obese patients were compared. CONCLUSIONS: Coordinated liver
      specific upregulation of genes involved in local cortisol regeneration and action
      support the concept that local hepatic hypercortisolism contributes to
      development of MS in morbidly obese patients.

PMID- 21964796
TI  - Effects of laparoscopic Roux-en-Y gastric bypass (LRYGB) on weight loss and
      biomarker parameters in morbidly obese patients: a 12-month follow-up.
AB  - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is suggested as the
      gold standard of the surgical techniques for morbid obesity treatment. The aim of
      this study was to evaluate the weight loss and biomarker parameter changes over a
      1-year period following LRYGB in Iranian morbidly obese patients. METHODS: Sixty
      patients who had undergone LRYGB from June 2006 to August 2008 were followed up.
      Complication rates and changes in anthropometric indices, metabolic parameters,
      and obesity-related comorbidities were evaluated. RESULTS: During the mean follow
      up duration of 27.2 +/- 9.4 months, the mean weight reduced from 128.8 +/- 20.4
      to 86.9 +/- 12.7 kg with excess weight loss (%EWL) of 63.8 +/- 15.6%. The male
      young-adolescent patients showed more weight loss than females. Biochemical
      parameter changes were reduction of fasting blood sugar by 19%, total cholesterol
      by 17%, triglyceride by 30%, low-density lipoprotein by 19%, aspartate
      aminotransferase by 44%, alanine aminotransferase by 52%, alkaline phosphatase by
      33%, and uric acid by 19%, while high-density lipoprotein (HDL) levels increased
      by 22%. HDL level change was the only biomarker factor showing correlation with
      age (P = 0.005, r = -0.353, R(2) = 0.125). Obesity comorbidities were resolved
      considerably. There were two cases of surgical complications and no case of
      mortality. CONCLUSION: LRYGB appears to be a safe and effective procedure with a
      low complication rate in Iranian morbidly obese patients. It results in weight
      loss, reduction in obesity comorbidities, increasing HDL, and decreasing other
      measured plasma biochemical parameters. Based on our results, we suggest that
      LRYGB would benefit young male morbidly obese patients more than others.

PMID- 21964797
TI  - Cervical cancer screening among HIV-infected women: an economic evaluation in a
      middle-income country.
AB  - Due to the recent widespread availability of highly active antiretroviral therapy
      (HAART) in middle-income countries, there has been an increase in life expectancy
      for women on HAART, but no corresponding decrease in cervical cancer incidence.
      This study evaluates the optimal cervical cancer screening strategy for HIV
      infected women in a middle-income country. We developed a mathematical model,
      which simulates the natural history of the HPV infection, as well as the HIV
      mediated immunosupression among women in Brazil. Our model was calibrated using
      data from the IPEC/FIOCRUZ Women's HIV-infected cohort. The model compares the
      lifetime effects, costs and cost-effectiveness of strategies combining cytology,
      HPV DNA test and colposcopy at different screening intervals for different CD4
      count strata (27 strategies in total). We found that the strategy with the best
      cost-effectiveness profile (cost-effectiveness ratio-U$4,911/year of life saved
      [YLS] and probability of being cost-effective-86%) was HPV testing followed by
      cytology triage every year for all HIV infected women, considering a very cost
      effective threshold given by Brazil's GDP per capita (US$8,625/YLS). The results
      were robust to changes in the input parameters as demonstrated in one-way,
      scenario, threshold and probabilistic sensitivity analysis. Our study indicates
      that annual HPV testing followed by cytology triage for all HIV-infected women is
      likely to be very cost-effective in a middle-income country like Brazil. The
      results reflect the synergic effect of using a highly sensitive screening test
      (HPV DNA test) in sequence with a highly specific test (cytology).

PMID- 21964799
TI  - Neuroprotective effects of PEP-1-Cu,Zn-SOD against ischemic neuronal damage in
      the rabbit spinal cord.
AB  - A rabbit model of spinal cord ischemia has been introduced as a good model to
      investigate the pathophysiology of ischemia-reperfusion (I-R)-induced paraplegia.
      In the present study, we observed the effects of Cu,Zn-superoxide dismutase
      (SOD1) against ischemic damage in the ventral horn of L(5-6) levels in the rabbit
      spinal cord. For this study, the expression vector PEP-1 was constructed, and
      this vector was fused with SOD1 to create a PEP-1-SOD1 fusion protein that easily
      penetrated the blood-brain barrier. Spinal cord ischemia was induced by transient
      occlusion of the abdominal aorta for 15 min. PEP-1-SOD1 (0.5 mg/kg) was
      intraperitoneally administered to rabbits 30 min before ischemic surgery. The
      administration of PEP-1-SOD1 significantly improved neurological scores compared
      to those in the PEP-1 (vehicle)-treated ischemia group. Also, in this group, the
      number of cresyl violet-positive cells at 72 h after I-R was much higher than
      that in the vehicle-treated ischemia group. Malondialdehyde levels were
      significantly decreased in the ischemic spinal cord of the PEP-1-SOD1-treated
      ischemia group compared to those in the vehicle-treated ischemia group. In
      contrast, the administration of PEP-1-SOD1 significantly ameliorated the ischemia
      induced reduction of SOD and catalase levels in the ischemic spinal cord. These
      results suggest that PEP-1-SOD1 protects neurons from spinal ischemic damage by
      decreasing lipid peroxidation and maintaining SOD and catalase levels in the
      ischemic rabbit spinal cord.

PMID- 21964800
TI  - Delayed administration of parecoxib, a specific COX-2 inhibitor, attenuated
      postischemic neuronal apoptosis by phosphorylation Akt and GSK-3beta.
AB  - Parecoxib is a recently described novel COX-2 inhibitor whose functional
      significance and neuroprotective mechanisms remain elusive. Therefore, in this
      study, we aimed to investigate whether delayed administration of parecoxib
      inhibited mitochondria-mediated neuronal apoptosis induced by ischemic
      reperfusion injury via phosphorylating Akt and its downstream target protein,
      glycogen synthase kinase 3beta (GSK-3beta). Adult male Sprague-Dawley rats were
      administered parecoxib (10 or 30 mg kg(-1), IP) or isotonic saline twice a day
      starting 24 h after middle cerebral artery occlusion (MCAO) for three consecutive
      days. Cerebral infarct volume, apoptotic neuron, caspase-3 immunoreactivity and
      the protein expression of p-Akt, p-GSK-3beta and Cytochrome C in cerebral
      ischemic cortex were evaluated at 96 h after reperfusion. Parecoxib significantly
      diminished infarct volume and attenuated neuron apoptosis in a dose-independent
      manner, compared with MCAO group alone. Increased p-Akt and p-GSK-3beta was
      observed in the ischemic penumbra of parecoxib group after stroke. Moreover,
      parecoxib also reduced the release of Cytochrome C from mitochondrial into
      cytosol and attenuated the caspase-3 immunoreactivity in the penumbra. Taken
      together, these results suggested that parecoxib ameliorated postischemic
      mitochondria-mediated neuronal apoptosis induced by focal cerebral ischemia in
      rats and this neuroprotective potential is involved in phosphorylation of Akt and
      GSK-3beta.

PMID- 21964801
TI  - Phase I dose-escalating study of panobinostat (LBH589) administered intravenously
      to Japanese patients with advanced solid tumors.
AB  - Panobinostat (LBH589) is a potent pan-histone deacetylase inhibitor. As a result
      of promising preclinical data, Phase I and II clinical trials of intravenous and
      oral panobinostat have been conducted in patients with a wide variety of
      hematologic and solid tumors. This is the first report of a phase I study to
      evaluate intravenous panobinostat given on days 1 and 8 of a 21-day cycle in
      patients with solid tumors. The primary objective was to characterize the safety
      and tolerability of panobinostat by evaluating the occurrence of dose-limiting
      toxicity (DLT) and determining the maximum tolerated dose (MTD) in Japanese
      patients with advanced solid tumors. Secondary objectives included characterizing
      the pharmacokinetics and assessing antitumor activity. Fourteen patients were
      assigned to three dose levels (Cohort 1: 10 mg/m(2) [three patients], Cohort 2:
      15 mg/m(2) [three patients], Cohort 3: 20 mg/m(2) [eight patients]), according to
      a standard "3 + 3" design. One patient who received 20 mg/m(2) had a DLT (grade 3
      elevation of gamma-glutamyl transpeptidase for >7 days). Thrombocytopenia was
      observed in all patients (grade 3 or 4 in 8), the severity of which was dependent
      on the dose and platelet count at baseline. The thrombocytopenia rapidly resolved
      within 8 days. Plasma panobinostat levels increased dose dependently, without
      clinically significant drug accumulation. Stable disease for >=4 months was
      observed in six patients; however, there were no complete or partial responses.
      It is feasible to conclude that 20 mg/m(2) was the MTD and recommend as the
      starting dose for phase II clinical trials.

PMID- 21964804
TI  - Global clinical trials are burdened by excessive bureaucracy, conference hears.

PMID- 21964802
TI  - Downregulation of CXCL12 signaling and altered hematopoietic stem and progenitor
      cell trafficking in a murine model of acute Anaplasma phagocytophilum infection.
AB  - Infection with a variety of bacterial pathogens results in hematopoietic stem and
      progenitor cell (HSPC) mobilization. The mechanism and kinetics of HSPC
      mobilization during infection are largely unknown. Previously, we found altered
      HSPC activity in bone marrow, spleen and blood during infection with Anaplasma
      phagocytophilum, the agent of granulocytic anaplasmosis. We hypothesized that
      altered CXCL12/CXCR4 signaling, a central pathway for HSPC homing to, and
      retention within, the bone marrow, plays a role in infection-induced alterations
      in HSPC number and trafficking. Mice were infected with A. phagocytophilum.
      Lineage-cKit+ HSPCs were enumerated and proliferation determined. CXCL12 and
      CXCR4 mRNA were quantified along with CXCL12 protein, and CXCR4 surface,
      intracellular and total protein expression in HSPCs was determined. Increased
      bone marrow proliferation of HSPCs began at 2 d post-infection followed by HSPC
      mobilization and splenic homing. Proliferation of resident HSPCs contributed to
      increased splenic HSPC numbers. Bone marrow CXCL12 mRNA and protein levels were
      decreased at 4-8 d post-infection concurrent with HSPC mobilization. CXCR4
      protein parameters were decreased in bone marrow HSPCs throughout 2-6 d post
      infection. Reduction of CXCL12/CXCR4 signaling simultaneously occurs with HSPC
      mobilization from bone marrow. Findings suggest that deranged CXCL12/CXCR4
      signaling plays a causal role in HSPC mobilization during acute A.
      phagocytophilum infection.

PMID- 21964805
TI  - Doctors who treated protesters in Bahrain are given 15 year sentences.

PMID- 21964806
TI  - Atypical presentation of pseudoxanthoma elasticum with abdominal cutis laxa:
      evidence for a spectrum of ectopic calcification disorders?
AB  - A patient is presented with severe cutis laxa of the abdomen. Molecular
      investigations, including sequencing of the fibulin-5 and elastin gene, failed to
      endorse the diagnosis of inherited cutis laxa. Ultrasonographical discovery of
      renal calcifications during his general work-up suggested a possible diagnosis of
      pseudo-xanthoma elasticum (PXE). A discrete yellowish reticular pattern in the
      anterior neck region was detected upon careful clinical examination. Clinically,
      the patient presented characteristics of both classic PXE (retinopathy, renal
      calcifications) and the PXE-like syndrome (cutis laxa beyond the flexural areas).
      Skin biopsy and ophthalmological examination confirmed the diagnosis of PXE. In
      addition, ultrastructural evaluation revealed calcium deposits in the periphery
      of elastic fibers, a typical observation in the PXE-like syndrome.
      Immunohistochemical experiments and ELISA tests for various inhibitors of
      calcification displayed results which were partly reminiscent of both PXE and the
      PXE-like syndrome. Molecular analysis revealed not only two ABCC6 mutations
      (related to PXE), but also a gain of function SNP in the GGCX gene, in which loss
      of-function mutations cause the PXE-like syndrome. We conclude that the patients
      phenotype and--to a further extent--the PXE-like syndrome, are part of a spectrum
      of ectopic calcification disorders which are clinically and/or pathogenetically
      related to PXE. The molecular findings in this patient are however insufficient
      to explain the entire phenotype and suggest a role for multiple genetic factors
      in soft tissue mineralization.

PMID- 21964808
TI  - The impact of retinoic acid treatment on the sensitivity of neuroblastoma cells
      to fenretinide.
AB  - Despite the successful introduction of 13-cis retinoic acid (13cisRA) therapy for
      the treatment of neuroblastoma, approximately 50% patients do not respond or
      experience relapse. A retinoid analogue, fenretinide [N-(4-hydroxyphenyl)
      retinamide; 4-HPR] can induce apoptosis in neuroblastoma cell lines and could
      have clinical use after therapy with 13cisRA. However, there are important
      questions concerning potential retinoid drug interactions which need to be
      addressed. The aim of this study was to investigate the influence of retinoic
      acid pre-treatment on fenretinide-induced apoptosis and fenretinide metabolism in
      neuroblastoma cell lines. Apoptosis was measured by flow cytometry of propidium
      iodide-stained neuroblastoma cells and a live-cell imaging assay. Intracellular
      fenretinide metabolism was determined by HPLC analysis. Pre-treatment of
      neuroblastoma cell lines with retinoic acid (RA) resulted in a significant
      decrease in the apoptotic response to fenretinide in three of the four lines
      tested. Comparison between responsive and non-responsive cell lines suggested
      that RA sensitivity was required to promote fenretinide resistance, and that this
      was mediated by up-regulation of Bcl-2 and the inhibition of pro-apoptotic
      fenretinide signalling pathways. Induction of the oxidative metabolism of
      fenretinide after RA pre-treatment did not significantly impact on intracellular
      parent drug levels and is unlikely to explain the decreased apoptotic response
      observed. The interaction between RA and fenretinide could have important
      implications for the scheduling of fenretinide in therapeutic protocols for
      neuroblastoma.

PMID- 21964809
TI  - Orientation of molecular groups of fibers in nonoriented samples determined by
      polarized ATR-FTIR spectroscopy.
AB  - A method based on polarized attenuated total reflection Fourier transform
      infrared (ATR-FTIR) spectroscopy is proposed for determining the infrared
      dichroic absorption ratio of a single fiber from a sample deposited flat on a
      germanium crystal without the requirement of fiber orientation. The method shows
      its efficiency on cellulose fibers of paper and has been applied to protein
      fibers (type I collagen and beta-amyloid) and polysaccharide fibers (cellulose
      and starch). The method gives access to the dichroic ratio of strong absorptions
      bands, which is not easily accessible with conventional absorption techniques.
      Then, the orientation of the molecular groups of organic fibers can be easily
      determined by polarized ATR-FTIR spectroscopy. By extension, this method will be
      useful to determine the molecular orientation of fibers in structured complex
      samples, such as biological tissues and plants. Spatially resolved information on
      the organization of the fiber network will be easily extracted by utilizing a
      focal plane array detector for imaging measurements.

PMID- 21964810
TI  - Evaluation of the performance of a tandem mass spectral library with mass
      spectral data extracted from literature.
AB  - MSforID represents a database of tandem mass spectral data obtained from (quasi
      )molecular ions produced by atmospheric pressure ionization methods. At the
      current stage of development the library contains 12 122 spectra of 1208 small
      (bio-)organic molecules. The present work was aimed to evaluate the performance
      of the MSforID library in terms of accuracy and transferability with a collection
      of fragment ion mass spectra from various compounds acquired on multiple
      instruments. A literature survey was conducted to collect the set of sample
      spectra. A total number of 554 spectra covering 291 compounds were extracted from
      109 publications. The majority of spectra originated from publications on
      applications of LC/MS/MS in drug monitoring, pharmacokinetics, environmental
      analysis, forensic analysis as well as food analysis. Almost all types of tandem
      mass spectrometric instruments distributed by the five most important instrument
      vendors were included in the study. The overall sensitivity of library search was
      found to be 96.4%, which clearly proves that the MSforID library can successfully
      handle data from a huge variety of mass spectrometric instruments to allow
      accurate compound identification. Only for spectra containing three or more
      fragment ions, however, the rate of classified matches (= matches with a relative
      average match probability (ramp) score > 40.0) was 95%. Ambiguous or unclassified
      results were mainly obtained for searches with single precursor-to-fragment ion
      transitions due to the insufficient specificity of such a low amount of
      structural information to unequivocally define a single compound.

PMID- 21964811
TI  - HistoFlex--a microfluidic device providing uniform flow conditions enabling
      highly sensitive, reproducible and quantitative in situ hybridizations.
AB  - A microfluidic device (the HistoFlex) designed to perform and monitor molecular
      biological assays under dynamic flow conditions on microscope slide-substrates,
      with special emphasis on analyzing histological tissue sections, is presented.
      Microscope slides were reversibly sealed onto a cast polydimethylsiloxane (PDMS)
      insert, patterned with distribution channels and reaction chambers. Topology
      optimization was used to design reaction chambers with uniform flow conditions.
      The HistoFlex provided uniform hybridization conditions, across the reaction
      chamber, as determined by hybridization to microscope slides of spotted DNA
      microarrays when applying probe concentrations generally used in in situ
      hybridization (ISH) assays. The HistoFlex's novel ability in online monitoring of
      an in situ hybridization assay was demonstrated using direct fluorescent
      detection of hybridization to 18S rRNA. Tissue sections were not visually damaged
      during assaying, which enabled adapting a complete ISH assay for detection of
      microRNAs (miRNA). The effects of flow based incubations on hybridization,
      antibody incubation and Tyramide Signal Amplification (TSA) steps were
      investigated upon adapting the ISH assay for performing in the HistoFlex. The
      hybridization step was significantly enhanced using flow based incubations due to
      improved hybridization efficiency. The HistoFlex device enabled a fast miRNA ISH
      assay (3 hours) which provided higher hybridization signal intensity compared to
      using conventional techniques (5 h 40 min). We further demonstrate that the
      improved hybridization efficiency using the HistoFlex permits more complex assays
      e.g. those comprising sequential hybridization and detection of two miRNAs to be
      performed with significantly increased sensitivity. The HistoFlex provides a new
      histological analysis platform that will allow multiple and sequential assays to
      be performed under their individual optimum assay conditions. Images can
      subsequently be recorded either in combination or sequentially through the
      ability of the HistoFlex to monitor assays without disassembly.

PMID- 21964812
TI  - High SMAD4 levels appear in microsatellite instability and hypermethylated colon
      cancers, and indicate a better prognosis.
AB  - Colorectal cancer (CRC) is one of the most common causes of cancer-related deaths
      in western countries. CRC are commonly divided in cancers showing microsatellite
      stability (MSS) or microsatellite instability (MSI). A more novel classification
      is dependent on promoter hypermethylation of CpG islands (the CpG island
      methylator phenotype, CIMP), where cancers show high, low or negative methylation
      status. SMAD4, located on chromosome 18q, has been thoroughly investigated during
      the last years. Loss of SMAD4 expression has been reported to correlate with poor
      CRC patient prognosis. In this study, we analyze the impact of SMAD4 expression
      on prognosis in relation to MSI screening status and CIMP status. Four hundred
      and seventy-nine paraffin-embedded specimens of CRC were examined for nuclear
      SMAD4 expression using immunohistochemistry. The tumors were scored loss (-),
      moderate (+) and high (++) expressing tumors. Loss of SMAD4 correlated
      significantly with decreased survival in all colon cancer patients. High SMAD4
      expression, however, was significantly associated with increased survival,
      especially in colon cancer patients, which has undergone potential curative
      surgery. In addition, in MSI tumors and CIMP-high tumors, high SMAD4 expression
      was significantly related to increase in survival, while loss of SMAD4 resulted
      in a significantly poorer prognosis. SMAD4 expression was not correlated to
      prognosis in rectal cancer cases. We conclude, loss of SMAD4 indicates a poor
      prognosis in colon cancer patients. The novel findings that high SMAD4 expression
      predicts a better prognosis suggests that SMAD4 immunohistochemistry could
      constitute a prognostic marker in combination with CIMP and MSI screening status.

PMID- 21964813
TI  - TNF-alpha blockers and carotid intima-media thickness: an emerging issue in the
      treatment of psoriatic arthritis.

PMID- 21964814
TI  - Sequential therapy in metastatic renal cell carcinoma: what comes next?

PMID- 21964815
TI  - 19-oxygenated ent-kaurane diterpenoids from Isodon pharicus.
AB  - Eight new 19-oxygenated ENT-kaurane diterpenoids were isolated from the aerial
      parts of Isodon pharicus. Their structures were determined by means of extensive
      spectroscopic techniques including interpretation of 1D and 2D NMR spectra.
      Selected compounds were evaluated for their cytotoxicity against NB4, A549, PC-3,
      MCF-7, and SH-SY5Y cell lines.

PMID- 21964816
TI  - Musculoskeletal impairment of traumatic etiology in Rwanda: prevalence, causes,
      and service implications.
AB  - BACKGROUND: The present study examines demographics, causes, and diagnoses of
      traumatic musculoskeletal impairment (MSI) in Rwanda and identifies treatment
      barriers in order to describe the injury burden and inform service planning.
      METHODS: In all, 105 clusters were chosen by multistage stratified cluster random
      sampling with probability proportional to size. Eighty people from each cluster
      were identified for screening by a modified compact segment sampling method. A
      screening questionnaire was applied and suspected cases and 10% of suspected non
      cases underwent standardized examination. A structured interview obtained a
      detailed history, and an algorithmic classification system allocated diagnosis.
      RESULTS: Of 8,368 enumerated subjects, 6,756 were screened. Of these, 111 were
      traumatic MSI cases, with 121 diagnoses, giving a prevalence of 1.64% (95% CI
      1.35-1.98). Extrapolation to the Rwandan population estimates 68,716 traumatic
      MSI cases, mostly in people of working age. Most affected were hand/finger joints
      (23%), elbow (16%), shoulder region (9%), and knee joint (9%). Some 11% of
      impairments were severe, 47.7% were moderate, and 41.3% were mild. Most common
      diagnoses were fracture malunion (21.5%) and post-traumatic joint stiffness
      (20.7%). The number of treatments needed was 199, including physiotherapy (87.2%)
      and surgery (53.7%), but 43% (95% CI 34-53) received less treatment than
      required. Of those who were undertreated, 63% cited cost. CONCLUSIONS: In Rwanda
      the prevalence of traumatic MSI of 1.64%, mostly in people of working age, makes
      usual activities difficult or impossible and is therefore a significant national
      burden. The results of the present study identify the need for immediate surgical
      intervention and physiotherapy, with cost as a treatment barrier. This study may
      direct aid providers toward subsidizing access to orthopedic care and thus reduce
      the impact of traumatic MSI.

PMID- 21964817
TI  - Risk factors and outcome of intra-abdominal hypertension in patients with severe
      acute pancreatitis.
AB  - BACKGROUND: Intra-abdominal hypertension (IAH) is common in patients with severe
      acute pancreatitis (SAP). The aim of the present study was to investigate the
      risk factors of IAH in SAP patients and assess the prognosis of SAP combined with
      IAH. METHODS: To analyze the data from patients with SAP, both univariate and
      multivariate logistic regression analyses were applied, using 16 indices,
      including age, gender, Acute Physiology and Chronic Health Evaluation II scores
      (APACHE II), 24 h fluid balance, hematocrit, serum calcium level, and so on.
      Clinical prognosis such as mortality, hospital duration, of SAP patients with or
      without IAH was also compared. RESULTS: First 24 h fluid balance (Odds Ratio
      [OR], 1.003; 95% Confidence Interval [CI], 1.001-1.006), number of fluid
      collections (OR, 1.652; 95% CI, 1.023-2.956), and serum calcium level (OR, 0.132;
      95% CI, 0.012-0.775) were found to be independent risk factors for IAH in
      patients with SAP. Moreover, patients with SAP and IAH had significantly longer
      average length of stay, both in the hospital and in the intensive care unit,
      higher rates of systemic and local complications, and more invasive treatments.
      CONCLUSIONS: The significant risk factors for IAH in patients with SAP include 24
      h fluid balance (first day), number of fluid collections, and serum calcium
      level. Additionally, IAH is associated with extremely poor prognosis, evidenced
      by high rates of mortality, morbidity, and the need for invasive interventions.

PMID- 21964818
TI  - Application of Variable Life Adjusted Display (VLAD) to risk-adjusted mortality
      of esophagogastric cancer surgery.
AB  - PURPOSE: In the new era of revalidation, there is an increasing need to measure
      surgical outcome objectively. We apply a graphical method, the Variable Life
      Adjusted Display (VLAD), to esophagogastric resection for malignancy. This
      technique charts the cumulative difference between expected and actual risk
      adjusted mortality over time, allowing observation of performance trends
      irrespective of case-mix. METHODS: P-POSSUM was applied retrospectively to 182
      consecutive patients who underwent resection for esophageal or gastric malignancy
      in a district general hospital. The primary outcome measured was 30-day
      mortality. RESULTS: A total of 168 patients were eligible for inclusion, with a
      median age of 68 years. The overall 30-day mortality rate was 4.2% compared with
      7.1% as predicted by P-POSSUM. The resulting VLAD plot demonstrates an upward
      trend of better than predicted surgical performance. CONCLUSIONS: VLAD has been
      hereby applied to esophagogastric surgery and has graphically demonstrated risk
      adjusted trends in a single general surgeon's performance. For qualitative
      comparative purposes, including recertification, VLAD is judged to be a simple,
      directly interpretable, and useful technique for monitoring surgical performance.

PMID- 21964820
TI  - Complex abdominal wall defects and enterocutaneous fistulae in the era of
      biological mesh: did we make any real progress?

PMID- 21964819
TI  - Surgery, public health, and Pakistan.
AB  - BACKGROUND: Surgical healthcare is rapidly gaining recognition as a major public
      health issue. Surgical disparities are large, with poorest populations receiving
      the least amount of emergency and essential surgical care. In light of recent
      evidence, developing countries, such as Pakistan, must acknowledge surgical
      disease as a major public health issue and prioritize research and intervention
      accordingly. METHODS: We review information from various sources and describe the
      current situation of surgical health care in Pakistan and highlight areas of
      neglect. RESULTS: Pakistan suffers an annual deficit of 17 million surgeries.
      Surgical disease kills more people than infectious diseases inclusive of
      tuberculosis, HIV/AIDS, diarrheal disease, and childhood infections. The
      incidence of trauma and maternal mortality ratio are staggeringly high. There is
      a severe dearth of surgical and anesthesia-related epidemiological data.
      Important information that would help to drive policy and planning is not
      available. Corruption and neglect have led to a dilapidated health care
      infrastructure. Surgical care is largely inaccessible to the poor, especially
      those living in rural areas. The country faces a dearth of healthcare
      professionals, especially paramedics, anesthetists, and surgeons. Unsafe surgery
      and anesthesia poses a significant risk to patients. There is no national policy
      on surgical illness and the preventive aspects of surgery are nonexistent.
      CONCLUSIONS: Consistent with other underdeveloped countries, surgical care in
      Pakistan is dismal. Neglecting surgery and safe anesthesia has led to countless
      deaths and disability. Physicians, researchers, policy makers, and the government
      health care system must engage and commit to provide access to emergency,
      essential, and safe surgical care.

PMID- 21964821
TI  - Genotype-phenotype correlation in migraine without aura focusing on the rs1835740
      variant on 8q22.1.
AB  - A large two-stage GWAS by Antilla et al. reported the minor allele of rs1835740
      on 8q22.1 to be associated with common types of migraine. The objective of the
      present study was to determine the clinical correlate of the variant in migraine
      without aura (MO). Clinical data on 339 successfully genotyped MO patients
      (patients with attacks of migraine without aura and no attacks of migraine with
      aura) were obtained by an extensive validated semi-structured telephone interview
      performed by a physician or a trained senior medical student. Reliable,
      systematic and extensive data on symptoms, age of onset, attack frequencies and
      duration, relevant comorbidity, specific provoking factors including different
      hormonal factors in females, and effect and use of medication, both abortive and
      prophylactic, were thereby obtained. A comparison of carriers and non-carriers
      were performed. Comparison of homozygotes with heterozygotes was not performed as
      the number of homozygotes was too small for statistical purposes. Data from other
      MO populations in the GWAS by Antilla et al. were not included as phenotype and
      clinical data were obtained differently. While thousands of patients are needed
      to detect a genetic variant like rs1835740, 339 are sufficient to detect
      meaningful clinical differences. 136 of 339 patients were carriers of the
      variant, 15 were homozygous. Comparison of carriers with non-carriers showed no
      significant difference in any of the parameters studied. In conclusion, the
      rs1835740 variant has no significant influence on the clinical expression of MO.

PMID- 21964822
TI  - Dye-guided retinal laser and internal drainage for optic pit maculopathy.

PMID- 21964823
TI  - Rapid increases in parasitemia following red cell exchange for malaria.
AB  - Exchange transfusion is frequently used as an adjunctive treatment of severe
      malaria, although the efficacy of exchange transfusion as therapy for severe
      malaria remains controversial. The major perceived benefit of exchange
      transfusion is the rapid reduction of parasite load. However, no previous report
      has shown the dynamic change in parasitemia shortly following an acute load
      reduction. We report a 20-year-female who developed cerebral malaria and 30%
      parasitemia after traveling to Africa. In addition to antimalarial treatment, red
      cell exchange (RCX) was begun emergently with an automated blood-cell separator.
      Parasitemia dropped from 30 to 15% immediately after the procedure but rapidly
      increased to 25% after 50 min. The second procedure was performed 12 h after the
      first procedure. Her neurologic status returned to baseline on Day 2, and she was
      discharged on Day 6. Rapid increases in parasitemia can be observed after
      mechanical load reduction following RCX.

PMID- 21964824
TI  - The relationship between the fear-avoidance model of pain and personality traits
      in fibromyalgia patients.
AB  - This study examined the relationship between several cognitive-affective factors
      of the fear-avoidance model of pain, the big five model of personality, and
      functional impairment in fibromyalgia (FM). Seventy-four FM patients completed
      the NEO Five-Factor Inventory, the Pain Catastrophizing Scale, the Pain Anxiety
      Symptoms Scale-20, the Pain Vigilance and Awareness Questionnaire, and the
      Impairment and Functioning Inventory. Results indicated that the cognitive
      affective factors of pain are differentially associated with personality traits.
      Neuroticism and conscientiousness were significant predictors of pain
      catastrophizing, and neuroticism, openness, and agreeableness were significant
      predictors of pain anxiety. Personality traits did not contribute significantly
      to vigilance to pain. The effect of neuroticism upon pain anxiety was mediated by
      pain catastrophizing, and neuroticism showed a trend to moderate the relationship
      between impairment and pain anxiety. Results support the fear-avoidance model of
      pain. Implications of the findings for the understanding and management of FM are
      discussed.

PMID- 21964825
TI  - The role of beliefs in the relationship between health problems and posttraumatic
      stress in adolescent and young adult cancer survivors.
AB  - In addition to the potential for ongoing health concerns, adolescent and young
      adult (AYA) childhood cancer survivors frequently report posttraumatic stress
      symptoms (PTSS). The current study examines whether beliefs about health moderate
      the relationship between the number of health problems and PTSS 2 months later in
      140 survivors. Beliefs, as measured by scales of the Health Competence Beliefs
      Inventory (HCBI), negatively related to PTSS while health problems positively
      related to PTSS. Three scales of the HCBI-health perceptions, satisfaction with
      healthcare and cognitive competence--were significant moderators. The
      relationship between health problems and PTSS was stronger in the presence of
      less adaptive beliefs. These beliefs represent potentially malleable intervention
      targets for reducing PTSS in childhood cancer survivors.

PMID- 21964827
TI  - The biology and evolution of polyspermy: insights from cellular and functional
      studies of sperm and centrosomal behavior in the fertilized egg.
AB  - Recent studies of centrosome biogenesis, microtubule dynamics, and their
      management point to their role in mediating conditions such as aging and cancer.
      Centrosome dysfunction is also a hallmark of pathological polyspermy. Polyspermy
      occurs when the oocyte is penetrated by more than one sperm and can be
      pathological because an excess of centrosomes compromises development. However,
      in some taxa, multiple sperm enter the egg with no apparent adverse effect on
      zygote viability. Thus, some taxa can manage excess centrosomes and represent
      cases of non-pathological polyspermy. While these two forms of polyspermy have
      long been known, we argue that there is limited understanding of the proximate
      and ultimate processes that underlie this taxonomic variation in the outcome of
      polyspermy and that studying this variation could help uncover the control and
      role(s) of centrosomes during fertilization in particular, but also mitosis in
      general. To encourage such studies we: 1) describe taxonomic differences in the
      outcome of polyspermy, 2) discuss mechanistic aspects of reproductive biology
      that may contribute to the different consequences of polyspermy, and 3) outline
      the potential selective events that could lead to the evolution of variation in
      polyspermy outcomes. We suggest that novel insights into centrosome biology may
      occur by cooperative studies between reproductive and evolutionary biologists
      focusing on the mechanisms generating variation in the fitness consequences of
      polyspermy, and in the taxonomic distribution of all these events. The consequent
      discoveries of these studies may lead to informative insights into cancer and
      aging along with other centrosome-related diseases and syndromes.

PMID- 21964826
TI  - Pediatrician identification of child behavior problems: the roles of parenting
      factors and cross-practice differences.
AB  - While most primary care pediatricians acknowledge the importance of identifying
      child behavior problems, fewer than 2% of children with a diagnosable
      psychological disorder are referred for mental health care in any given year. The
      present study examined the potential role of parental characteristics (parental
      affect, parenting style, and parenting self-efficacy) in pediatrician
      identification of child behavior problems, and determined whether these
      relationships differed across practices. Parents of 831 children between 2 and 16
      years completed questionnaires regarding demographic information, their child's
      behavior, their affect, their parenting style, and their parenting self-efficacy.
      Pediatricians completed a brief questionnaire following visits in four community
      based primary care practices in the Midwest. Logistic regressions controlling for
      child behavior and demographic predictors of pediatrician identification found
      that an authoritarian parenting style, in which parents yell or strongly
      negatively react to problem behavior, was negatively associated with likelihood
      of identification in the overall sample. However, the variables that were
      predictive of pediatrician identification differed depending on the specific
      practice. Parental characteristics can aid in understanding which children are
      likely to be identified by their pediatrician as having behavioral problems. The
      finding that practices differed on which variables were associated with
      pediatrician identification suggests the need to potentially individualize
      interventions to certain physicians and practices to improve identification of
      child behavior problems in primary care.

PMID- 21964828
TI  - Sperm surface changes and physiological consequences induced by sperm handling
      and storage.
AB  - Spermatozoa interact with their immediate environment and this contact remodels
      the sperm surface in preparation for fertilisation. These fundamental membrane
      changes will be critically covered in this review with special emphasis on the
      very specific surface destabilisation event, capacitation. This process involves
      very subtle and intricate modifications of the sperm membrane including removal
      of suppression (decapacitation) factors and changes in the lateral organisation
      of the proteins and lipids of the sperm surface. Processing of sperm for assisted
      reproduction (storage, sex-sorting, etc.) subjects spermatozoa to numerous
      stressors, and it is possible that this processing overrides such delicate
      processes resulting in sperm instability and cell damage. To improve sperm
      quality, novel mechanisms must be used to stabilise the sperm surface during
      handling. In this review, different types of membrane stress are considered, as
      well as novel surface manipulation methods to improve sperm stability.

PMID- 21964829
TI  - Fetal akinesia in metatropic dysplasia: The combined phenotype of
      chondrodysplasia and neuropathy?
AB  - Dominant mutations in the receptor calcium channel gene TRPV4 have been
      associated with a family of skeletal dysplasias (metatropic dysplasia, pseudo
      Morquio type 2, spondylometaphyseal dysplasia, Kozlowski type, brachyolmia, and
      familial digital arthropathy) as well as with dominantly inherited neuropathies
      (hereditary motor and sensory neuropathy 2C, scapuloperoneal spinal muscular
      atrophy, and congenital distal spinal muscular atrophy). While there is
      phenotypic overlap between the various members of each group, the two groups were
      considered to be totally separate with the former being strictly a structural
      skeletal condition and the latter group being confined to the peripheral nervous
      system. We report here on fetal akinesia as the presenting feature of severe
      metatropic dysplasia, suggesting that certain TRPV4 mutations can cause both a
      skeletal and a neuropathic phenotype. Three cases were detected on prenatal
      ultrasound because of absent movements in the second trimester. Case 4 presented
      with multiple joint contractures and absent limb movements at birth and was
      diagnosed with "fetal akinesia syndrome". Post-interruption and post-natal X-rays
      showed typical features of metatropic dysplasia in all four. Sequencing of the
      TRPV4 gene confirmed the presence of de novo heterozygous mutations predicting
      G78W (Case 1), T740I (Cases 2 and 3), and K276E (Case 4). Although some degree of
      restriction of movements is not uncommon in fetuses with skeletal dysplasia,
      akinesia as leading sign is unusual and suggests that certain TRPV4 mutations
      produce both chondrodysplasia and a peripheral neuropathy resulting in a severe
      "overlap" phenotype.

PMID- 21964830
TI  - OTX2 directly activates cell cycle genes and inhibits differentiation in
      medulloblastoma cells.
AB  - The transcription factor OTX2 has been implicated as an oncogene in
      medulloblastoma, which is the most common malignant brain tumor in children. It
      is highly expressed in most medulloblastomas and amplified in a subset of them.
      To study the role OTX2 has in medulloblastoma we investigated the downstream
      pathway of OTX2. We generated D425 medulloblastoma cells in which endogenous OTX2
      can be silenced by inducible shRNA. Silencing of OTX2 strongly inhibited cell
      proliferation and resulted in a neuronal-like differentiation. Expression
      profiling of time courses after silencing showed a progressive change in gene
      expression for many cellular processes. Downregulated genes were highly enriched
      for cell cycle and visual perception genes, while upregulated genes were enriched
      for genes involved in development and differentiation. This shift is reminiscent
      of expression changes described during normal cerebellum development where
      proliferating granule progenitor cells have high OTX2 expression, which
      diminishes when these cells exit the cell cycle and start to differentiate. ChIP
      on-chip analyses of OTX2 in D425 cells identified cell cycle and perception genes
      as direct OTX2 targets, while regulation of most differentiation genes appeared
      to be indirect. The expression of many directly regulated genes correlated to
      OTX2 expression in primary tumors, suggesting the in vivo relevance of these
      genes and their potential as targets for therapeutic intervention. These analyses
      provide more insight in the molecular network of OTX2, demonstrating that OTX2 is
      essential in medulloblastoma and directly drives proliferation by regulation of
      cell cycle genes.

PMID- 21964831
TI  - A response to: loss of dermatan-4-sulfotransferase 1 (D4ST1/CHST14) function
      represents the first dermatan sulfate biosynthesis defect, "dermatan sulfate
      deficient Adducted Thumb-Clubfoot Syndrome". Which name is appropriate, "Adducted
      Thumb-Clubfoot Syndrome" or "Ehlers-Danlos syndrome"?

PMID- 21964832
TI  - Effect of berberine on p53 expression by TPA in breast cancer cells.
AB  - Berberine (BBR), an isoquinoline derivative alkaloid compound, has been reported
      to have anti-oxidant and anti-carcinogenic effects. A loss of functional p53 is
      involved with an increased risk of cancer proliferation and metastasis. Here, we
      investigated the effect of BBR on the transcriptional activity and the protein
      expression of p53 in p53-positive (wild- type, MCF7 cells) and p53-negative
      (mutant, MDA-MB231 cells) human breast cancer cells. Our results showed that the
      basal level of p53 mRNA and protein expression was increased by BBR treatment.
      However, tumor promoter, TPA, decreased the level of p53 mRNA and protein
      expression in MCF7 cells with wild-type p53. In addition, TPA-induced down
      regulation of p53 mRNA and protein expression was increased by UO126, but not by
      SP600125 and SB203580. To verify the regulatory mechanism of p53 protein
      expression, we investigated the effects of proteasomal inhibitors (ALLN and
      MG132) or a lysosomal inhibitor (chloroquine) on TPA-induced down-regulation of
      p53. We observed that TPA-induced down-regulation of p53 protein was prevented by
      ALLN and MG132, but not by chloroquine. Further, we investigated the effect of
      BBR on TPA-induced down-regulation of p53 mRNA and protein levels. Interestingly,
      the levels of TPA-induced down-regulation of p53 mRNA and protein were prevented
      by BBR, but MDA-MB231 cells with mutated p53 were not affected. In addition, TPA
      induced down-regulation of p53 mRNA was also prevented by BBR. Taken together, we
      suggest that BBR may be used as an effective ingredient for anticancer products,
      which trigger the transcriptional activity and the inhibition of the degradation
      of p53, a tumor suppressor gene, in human breast cancer.

PMID- 21964833
TI  - A "little western flower" challenge.

PMID- 21964834
TI  - Solution to living cell spectroscopy challenge.

PMID- 21964835
TI  - Is amoxicillin plus clavulanic acid non-inferior to appendicectomy for the
      treatment of uncomplicated acute appendicitis?

PMID- 21964836
TI  - An over-the-counter weight-loss supplement with a toxicity that may be
      unexpectedly difficult to treat.

PMID- 21964837
TI  - A practical approach to diagnosis and management of functional constipation in
      adults.
AB  - Chronic constipation is a frequently complained condition in clinical practice
      and may be primary (idiopathic) or due to secondary causes. The definition of the
      various forms of constipation is presently made according to the Rome III
      criteria, which recently incorporated also specific diagnostic algorithms. The
      diagnosis of constipation relies on the patient's history, including use of
      drugs, physical examination, and specific investigations (transit time, anorectal
      manometry, balloon expulsion test, defecography). These will often be useful to
      start a targeted therapeutic schedule that may include fibres, laxatives,
      biofeedback training and, in extreme cases, a surgical approach. This review will
      analyse the clinical and diagnostic aspects of chronic constipation in adult
      patients, with emphasis on recent therapeutic approaches.

PMID- 21964838
TI  - COPD and the metabolic syndrome: an intriguing association.
AB  - Chronic Obstructive Pulmonary Disease (COPD) has been recently recognized as a
      condition involving more than the lungs. The presence of common factors in COPD
      and in other chronic extra-pulmonary diseases, as well as the co-existence of
      these conditions in the same adult individual, supports the hypothesis of a
      shared pathogenetic pathway. We will here review the interplay between coexisting
      COPD and the metabolic syndrome (MS), based on the most updated knowledge. We
      will discuss this clinical condition from the definition, to the pathophysiology
      and to the clinical implications. Basically, MS is more likely to be present in a
      COPD patients, and increased levels of circulatory pro-inflammatory proteins from
      both the lung and adipose tissue coincide in these patients. The relative impact
      of the coexisting COPD and MS may depend on several factors: the presence of
      physical inactivity and of systemic inflammation related to a smoking habit,
      sedentary lifestyle, airway inflammation and obstruction, adipose tissue and
      inflammatory marker activation. More studies will be required to elucidate the
      association between COPD and MS and to formulate individualized management
      approaches for this specific disease phenotype.

PMID- 21964839
TI  - Extra-fibrillar matrix mechanics of annulus fibrosus in tension and compression.
AB  - The annulus fibrosus (AF) of the disk is a highly nonlinear and anisotropic
      material that undergoes a complex combination of loads in multiple orientations.
      The tensile mechanical behavior of AF in the lamellar plane is dominated by
      collagen fibers and has been accurately modeled using exponential functions. On
      the other hand, AF mechanics perpendicular to the lamella, in the radial
      direction, depend on the properties of the ground matrix with little to no fiber
      contribution. The ground matrix is mainly composed of proteoglycans (PG), which
      are negatively charged macromolecules that maintain the tissue hydration via
      osmotic pressure. The mechanical response of the ground matrix can be divided in
      the contribution of osmotic pressure and an elastic solid part known as extra
      fibrillar matrix (EFM). Mechanical properties of the ground matrix have been
      measured using tensile and confined compression tests. However, EFM mechanics
      have not been measured directly. The objective of this study was to measure AF
      nonlinear mechanics of the EFM in tension and compression. To accomplish this, a
      combination of osmotic swelling and confined compression in disk radial
      direction, perpendicular to the lamella, was used. For this type of analysis, it
      was necessary to define a stress-free reference configuration. Thus, a brief
      analysis on residual stress in the disk and a procedure to estimate the reference
      configuration are presented. The proposed method was able to predict similar
      swelling deformations when using different loading protocols and models for the
      EFM, demonstrating its robustness. The stress-stretch curve of the EFM was linear
      in the range 0.9 < lambda3 < 1.3 with an aggregate modulus of 10.18+/-3.32 kPa;
      however, a significant nonlinearity was observed for compression below 0.8. The
      contribution of the EFM to the total aggregate modulus of the AF decreased from
      70 to 30% for an applied compression of 50% of the initial thickness. The
      properties obtained in this study are essential for constitutive and finite
      element models of the AF and disk and can be applied to differentiate between
      functional degeneration effects such as PG loss and stiffening due to cross
      linking.

PMID- 21964841
TI  - Emerging and controversial issues in neurology: infectious diseases. Preface.

PMID- 21964843
TI  - Issues and updates in emerging neurologic viral infections.
AB  - This review discusses the recent advances in the identification of viral
      pathogens and other etiologies responsible for cases of suspected viral
      encephalitis. The authors describe new molecular diagnostic strategies for
      identifying novel causes of viral encephalitis, including MassTag PCR, DNA
      microarrays, and high-throughput DNA pyrosequencing. They also highlight the
      increasing recognition of immune-mediated causes of encephalitis among those
      cases previously thought to be viral encephalitis of unknown etiology. Lastly,
      they review some of the most recent updates in the field of emerging neurologic
      viral infections impacting the United States, including the neurologic
      complications of H1N1 virus and the reemergence of dengue virus in the Florida
      Keys.

PMID- 21964842
TI  - Neurologic parasitic infections in immigrants and travelers.
AB  - Infectious diseases are increasingly common in modern clinical practice and the
      contemporary neurologist must be aware of the clinical manifestations, potential
      complications, and management of common travel-related infections. The authors
      provide an approach to patients who present with neurologic symptoms, with a
      history of travel to or residence in tropical and developing countries. Although
      many other infections are important in this demographic, they focus on three
      parasitic infections that neurologists may encounter: cerebral malaria,
      neuroschistosomiasis, and neurocysticercosis. The epidemiology, pathophysiology,
      clinical manifestations, diagnostic evaluation, and treatment are discussed for
      each infection.

PMID- 21964844
TI  - Atypical nervous system manifestations of HIV.
AB  - Despite the widespread success of combination antiretroviral therapy (cART) in
      reducing morbidity and mortality in human immunodeficiency virus 1 (HIV-1)
      infection, HIV-associated neurologic disease remains prevalent. Although the
      virus is unable to infect neurons or muscle fibers directly, it can still injure
      these structures by a variety of mechanisms, many of which are yet to be
      elucidated. Additionally, antiretroviral medications used to treat HIV infection
      can cause damage to the nervous system both by direct toxicity and via modulation
      of host-virus interactions. Some neurologic complications of HIV infection are
      rarely seen and are poorly understood; nevertheless, they are important to
      recognize. In this review article, the authors focus on the uncommon neurologic
      manifestations of HIV infection, including mononeuropathies, inflammatory
      demyelinating polyneuropathies, motor neuron disease, polymyositis, diffuse
      infiltrative lymphocytosis syndrome, mononeuritis multiplex, HIV-associated
      neuromuscular weakness syndrome, immune reconstitution inflammatory syndrome, and
      central nervous system HIV-escape meningoencephalomyelitis and myelitis.

PMID- 21964845
TI  - Infectious causes of rapidly progressive dementia.
AB  - Infections represent an uncommon but important to recognize cause of rapidly
      progressive dementia, as diagnosis and treatment may produce a favorable outcome
      in selected instances. This article reviews infectious causes of rapidly
      progressive dementia, including selected viruses, bacteria, fungi, parasites, and
      prion diseases. Epidemiology, clinical manifestations, imaging characteristics,
      laboratory diagnosis, and treatment options are discussed.

PMID- 21964846
TI  - Cerebrovascular disease in central nervous system infections.
AB  - Cerebrovascular disease is a complication of a variety of infections affecting
      the central nervous system (CNS). Infection may cause vasculitis affecting
      primarily the vessels at the base of the brain in the setting of meningitis; an
      immune-mediated parainfectious process leading to vasospasm or thrombosis; or a
      hypercoagulable state in combination with endothelial dysfunction resulting from
      activation of inflammatory and procoagulant cascades. Although systemic signs and
      symptoms may be present to aid in the diagnosis, cerebral infarction secondary to
      infection may be indistinguishable from more typical causes of stroke.
      Confirmation of an infectious vasculitis may also be challenging, as brain
      biopsy, the gold standard for diagnosis, is rarely pursued. In many CNS
      infections, vascular complications portend a poor prognosis as they are often
      associated with devastating neurologic outcomes, including death, underscoring
      the importance of early recognition and appropriate therapy. In this review, we
      address bacterial, viral, fungal, and parasitic causes of cerebrovascular
      disease.

PMID- 21964847
TI  - Evidence for viral etiology of multiple sclerosis.
AB  - The etiology of multiple sclerosis (MS) is unknown, and several hypotheses have
      been advanced over the past century to explain it. Despite much effort, no single
      cause has been established. One of the most appealing hypotheses is that of
      infection due to a neurotropic infectious agent, possibly a virus. There are
      several lines of data to support this hypothesis. First, there are clear examples
      of inflammatory demyelinating disease caused directly or indirectly by viral
      infections in both humans and animals. Second, there is a strong environmental
      component to multiple sclerosis. Finally, there is aberrant immune reactivity
      against various viruses. Recent candidates have included measles and the related
      canine distemper virus, human herpesvirus 6, human endogenous retroviruses, and
      Epstein-Barr virus. The evidence is most extensive for the latter and will be
      discussed in some detail.

PMID- 21964848
TI  - Nervous system lyme disease: is there a controversy?
AB  - Infection with the tick-borne spirochete,  BORRELIA BURGDORFERI, affects the
      nervous system in well-defined ways. Accurate diagnostic tools and effective
      therapeutic regimens are now well established. Persistent misconceptions about
      (1) the role and interpretation of laboratory tests, (2) what is and is not
      evidence of nervous system infection, and (3) what constitutes an expected
      response to treatment have fostered widespread perceptions that this disease is
      highly controversial. Infection causes the classically described triad of
      meningitis, radiculoneuritis, and cranial neuritis; however, virtually every
      known neurologic disorder has been blamed on this infection. For most (multiple
      sclerosis, amyotrophic lateral sclerosis, Alzheimer disease, Parkinson disease),
      evidence is scant, nonexistent, or coincidental. For some (cerebral vasculitis
      with stroke, optic neuritis) a few case reports suggest a rare possible causal
      link.

PMID- 21964849
TI  - Role of infection and neurologic dysfunction in chronic fatigue syndrome.
AB  - Chronic fatiguing illnesses following well-documented infections and acute
      "infectious-like" illnesses of uncertain cause have been reported for many
      decades. Chronic fatigue syndrome (CFS) was first formally defined in 1988. There
      is considerable evidence that CFS is associated with abnormalities of the central
      and autonomic nervous systems. There also is evidence linking several infectious
      agents with CFS, although no agent has been proven to be a cause of the illness.
      Most of the infectious agents that have been linked to CFS are able to produce a
      persistent, often life-long, infection and thus are a constant incitement to the
      immune system. Most also have been shown to be neuropathogens. The evidence is
      consistent with the hypothesis that CFS, in some cases, can be triggered and
      perpetuated by several chronic infections that directly or indirectly affect the
      nervous system, and that symptoms are a reflection of the immune response to the
      infection.

PMID- 21964850
TI  - Vaccines and neurologic disease.
AB  - Vaccines have undoubtedly been a medical milestone, preventing immeasurable
      morbidity and mortality from infectious diseases worldwide. Modern vaccines have
      tremendously reduced the global impact of numerous infections; they have
      succeeded in eliminating smallpox completely. However, the nature by which
      vaccines confer their protection-by stimulation of the immune system-means that
      in rare cases, adverse often immunologically mediated events may occur following
      vaccination. Some of the most severe of these involve the nervous system. The
      author provides an overview of the mechanisms of vaccinology, and describes the
      various vaccines available for particular neurologic illnesses. Possible
      neurologic adverse events following vaccinations, and the possible mechanisms of
      these events, are also discussed. Finally, procedures in place to ensure vaccine
      safety are reviewed.

PMID- 21964851
TI  - Anatomic response of occult choroidal neovascularization to intravitreal
      ranibizumab: a study by indocyanine green angiography.
AB  - BACKGROUND: To investigate changes in indocyanine green angiography (ICGA)
      features of occult choroidal neovascularization (CNV) after intravitreal
      ranibizumab injections. METHODS: We reviewed the charts of all consecutive
      patients with newly diagnosed occult CNV secondary to age-related macular
      degeneration (AMD) treated by intravitreal ranibizumab. In all patients, optical
      coherence tomography (OCT) and ICGA were performed at baseline, after 3 months
      and 12 months. RESULTS: Fifty-one eyes of 44 patients (ten males, 34 females,
      mean age 77.8 +/- 7.3 years) were included. Mean follow-up was 20.3 +/- 6.2
      months. During the first 12 months, patients received 5.5 +/- 2.7 intravitreal
      ranibizumab injections. When compared with baseline, best-corrected visual acuity
      (BCVA) significantly improved at the 3-month follow-up visit (60.5 +/-22.0 vs
      50.9 +/-20.7 letters, p = 0.04), and stabilized at 12-month visit (55.7 +/-18.2
      letters; p = 0.05). Central macular thickness (CMT) significantly improved during
      follow-up (229.0 +/-54.7 MUm vs 281.0 +/-61.3 MUm at baseline, p = 0.003). An
      overall stabilization was observed on ICGA in both the lesion area (5.27 +/- 3.9
      mm(2) at baseline vs 4.60 +/- 3.5 mm(2) at month 12, p = 0.4), and greatest
      linear dimension (GLD 2.66 +/- 1.2 mm at baseline vs 2.55 +/- 1.0 mm at month 12,
      p = 0.3). Eight eyes (15.7%) showed CNV growth on ICGA (lesion area 3.98 +/- 3.2
      mm2 at baseline vs 4.3 +/- 2.7 mm2 at month-12, p = 0.6; GLD 2.11 +/- 1.0 mm at
      baseline vs 2.70 +/- 0.8 mm at month-12, p = 0.05). CONCLUSION: ICGA suggests
      that functional outcomes after intravitreal ranibizumab is related to CMT
      reduction rather than CNV regression.

PMID- 21964852
TI  - Argentine ant trail pheromone disruption is mediated by trail concentration.
AB  - Argentine ant trail pheromone disruption, using continuous release of the trail
      pheromone compound (Z)-9-hexadecanal, reduces the incidence of trails and
      foraging rates of field populations. However, little is known about the
      concentrations of pheromone required for successful disruption. We hypothesized
      that higher pheromone quantities would be necessary to disrupt larger ant
      populations. To test this, we laid a 30-cm long base trail of (Z)-9-hexadecanal
      on a glass surface at low and high rates (1 and 100 pg/cm) (Trail 1), and laid a
      second, shorter trail (Trail 2, 10 cm long, located 1.5 cm upwind) near the
      middle of Trail 1 at six rates (1, 10, 100, 1,000, 10,000, and 100,000 pg/cm). We
      then recorded and digitized movements of individual ants following Trail 1, and
      derived a regression statistic, r (2), as an index of trail integrity, and also
      recorded arrival success at the other end of the trail (30 cm) near a food
      supply. Disruption of trails required 100 fold more pheromone upwind, independent
      of base-trail concentration. This implies that in the field, trail disruption is
      likely to be less successful against high ant-trail densities (greater
      concentration of trail pheromone), and more successful against newly formed or
      weak trails, as could be expected along invasion fronts.

PMID- 21964853
TI  - Uranium in vegetable foodstuffs: should residents near the Cunha Baixa uranium
      mine site (Central Northern Portugal) be concerned?
AB  - Large uranium accumulations in vegetable foodstuffs may present risks of human
      health if they are consumed. The objective of this study was to evaluate the
      uranium concentrations in different vegetable foodstuffs and grown in
      agricultural soils, which are then consumed by the residents of the village of
      Cunha Baixa (Portugal),--located in an former uranium mining area. This study was
      conducted to address concerns expressed by the local farmers as well as to
      provide data for uranium-related health risk assessments for the area. Soils,
      irrigation water and edible tissues of lettuce, potato, green bean, carrot,
      cabbage, apple and maize (Latuca sativa L., Solanum tuberosum L., Phaseolus
      vulgaris L., Daucus carota L., Brassica oleracea L., Malus domestica Borkh, Zea
      mays L., respectively) were sampled and uranium determined. High uranium
      concentrations were found in some soils (U(total) > 50 mg/kg), in irrigation
      waters (218 to 1,035 MUg/l) and in some vegetable foodstuffs (up to 234, 110, 30,
      26, 22, 16 and 1.6 MUg/kg fresh weight for lettuce, potato with peel, green bean
      pods, cabbage, corn, carrot and apple, respectively). However, the results of the
      toxicity hazard analysis were reassuring the estimated level of uranium exposure
      through the ingestion of these vegetable foodstuffs was low, suggesting no
      chemical health risk (hazard quotient <1) to this uranium exposure pathway for a
      local residents during their lifetime, even for the most sensitive part of the
      population (child).

PMID- 21964854
TI  - Metal fractionation of cadmium, lead and arsenic of geogenic origin in topsoils
      from the Marrancos gold mineralisation, northern Portugal.
AB  - The Marrancos gold mineralisation has a chemical assemblage of Fe-As-Se-Bi-Au-Ag
      Te-(Cu-Pb-Zn-Sn-W). The -200 mesh of 144 topsoil samples was analysed by ICP-MS
      to determine total contents of 53 elements that include potentially harmful
      elements like Cd, As and Pb. The soil geochemistry shows that some trace elements
      occur in considerably high concentrations. On the basis of data for total metal
      concentrations, 10 topsoil samples were selected to carry out a metal
      fractionation study using a selective extraction method. A set of four leaches of
      increasing strength was used sequentially in the soil samples. Across the study
      area, there is some evidence of past mining and exploration activity, indicating
      that these soils may be locally disturbed. The shallow mineralised quartz veins
      were exploited for gold by the Romans. Several galleries were constructed during
      the 2nd World War, probably for the exploration of quartz-cassiterite-wolframite
      veins. However, the main mineralised body in depth was never explored. The
      results of metal fractionation show different partitions for the three elements.
      Total Cd concentrations in these soils are low, with a median value of 0.1 mg/kg.
      In average, 12% of total Cd is adsorbed by clays and/or co-precipitated with
      carbonates, and 19% is bounded to Fe-Mn oxyhydroxides. However, the low
      concentrations indicate that the metal does not represent an immediate risk to
      human health. For Pb, metal fractionation shows that, on average, 22% of Pb is
      adsorbed by amorphous Fe and Mn oxides, but the samples from the northern part of
      the area have the major fractions of Pb in soluble forms. The low probability of
      exposure in this part of the study area decreases the risk posed by this heavy
      metal. Total As concentrations in the Marrancos soils are extremely high. A large
      area has As concentrations above 1,000 mg/kg. For As, metal fractions in the
      sulphide phase vary between 84 and 98% in the studied samples. But one sample has
      20% of total As in easily reducible forms, corresponding to a partial
      concentration of 1,800 mg/kg that has a high probability of being bioavailable.
      The most labile As forms occur at the southern part of the area, where the
      probability of exposure is higher and the risk of human health increases in the
      same order. From the three studied potentially harmful elements, As is certainly
      the element of concern.

PMID- 21964855
TI  - Physico-chemical characteristics of the peloid mud from Morinje Bay (eastern
      Adriatic coast, Croatia): suitability for use in balneotherapy.
AB  - The study conducted in the Morinje Bay (Central Dalmatia, Croatia) included the
      investigation of the sedimentological, physico-chemical and geochemical
      properties of the Morinje Bay sediments in order to assess the suitability of the
      material for wellness-related purposes including medicinal use. The
      sedimentological characteristics of the Morinje mud are in accordance with the
      geological origin of the material; the sediment is fine grained, composed mostly
      of carbonates, quartz and clay minerals. The composition of the sediment
      determines the physico-chemical properties of the mud. The high content of
      carbonate minerals diminishes adsorbing the characteristics of the mud to some
      extent; however, they are still comparable to some commercial mud already
      successfully used for medicinal purposes. Geochemical analyses have shown that
      trace metals concentrations in the Morinje Bay samples were mostly in the range
      with similar material from unpolluted Adriatic environments. Only the
      concentrations of Cu, Pb, Zn and As were slightly higher than in the reference
      material, but still within acceptable limits.

PMID- 21964856
TI  - Automated method for the determination of total arsenic and selenium in natural
      and drinking water by HG-AAS.
AB  - A multicommutated flow system was designed and evaluated for the determination of
      total arsenic and selenium by Hydride Generation Atomic Absorption Spectrometry
      (HG-AAS). It was applied to the determination of arsenic and selenium in samples
      of natural and drinking water. Detection limits were 0.46 and 0.08 MUg l(-1) for
      arsenic and selenium, respectively; sampling frequency was 120 samples h(-1) for
      arsenic and 160 samples h(-1) for selenium. Linear ranges found were 1.54-10 MUg
      l(-1) (R = 0.999) for arsenic and 0.27-27 MUg l(-1) (R = 0.999) for selenium.
      Accuracy was evaluated by spiking various water samples and using a reference
      material. Recoveries were in the range 95-116%. Analytical precision (s ( r )
      (%), n = 10) was 6% for both elements. Compared with the Standard Methods, APHA,
      3114B manual method, the system consumes at least 10 times less sample per
      determination, and the quantities of acid and reducing agent used are
      significantly lower with a reduction in the generation of pollutants and waste.
      As an additional advantage, the system is very fast, efficient and
      environmentally friendly for monitoring total arsenic and selenium levels in
      waters.

PMID- 21964857
TI  - Hyaluronan within fascia in the etiology of myofascial pain.
AB  - The layers of loose connective tissue within deep fasciae were studied with
      particular emphasis on the histochemical distribution of hyaluronan (HA). Samples
      of deep fascia together with the underlying muscles were taken from neck, abdomen
      and thigh from three fresh non-embalmed cadavers. Samples were stained with
      hematoxylin-eosin, Azan-Mallory, Alcian blue and a biotinylated HA-binding
      protein specific for HA. An ultrasound study was also performed on 22 voluntary
      subjects to analyze the thickness of these deep fasciae and their sublayers. The
      deep fascia presented a layer of HA between fascia and the muscle and within the
      loose connective tissue that divided different fibrous sublayers of the deep
      fascia. A layer of fibroblast-like cells that stained prominently with Alcian
      blue stain was observed. It was postulated that these are cells specialized for
      the biosynthesis of the HA-rich matrix. These cells we have termed "fasciacytes",
      and may represent a new class of cells not previously recognized. The ultrasound
      study highlighted a mean thickness of 1.88 mm of the fascia lata, 1.68 mm of the
      rectus sheath, and 1.73 mm of the sternocleidomastoid fascia. The HA within the
      deep fascia facilitates the free sliding of two adjacent fibrous fascial layers,
      thus promoting the normal function associated with the deep fascia. If the HA
      assumes a more packed conformation, or more generally, if the loose connective
      tissue inside the fascia alters its density, the behavior of the entire deep
      fascia and the underlying muscle would be compromised. This, we predict, may be
      the basis of the common phenomenon known as "myofascial pain."

PMID- 21964858
TI  - Dynamic measurement of the height and volume of migrating cells by a novel
      fluorescence microscopy technique.
AB  - We propose a new technique to measure the volume of adherent migrating cells. The
      method is based on a negative staining where a fluorescent, non-cell-permeant dye
      is added to the extracellular medium. The specimen is observed with a
      conventional fluorescence microscope in a chamber of uniform height. Given that
      the fluorescence signal depends on the thickness of the emitting layer, the
      objects excluding the fluorescent dye (i.e., cells) appear dark, and the decrease
      of the fluorescent signal with respect to the background is expected to give
      information about the height and the volume of the object. Using a glass
      microfabricated pattern with steps of defined heights, we show that the drop in
      fluorescence intensity is indeed proportional to the height of the step and
      obtain calibration curves relating fluorescence intensity to height. The
      technique, termed the fluorescence displacement method, is further validated by
      comparing our measurements with the ones obtained by atomic force microscopy
      (AFM). We apply our method to measure the real-time volume dynamics of migrating
      fish epidermal keratocytes subjected to osmotic stress. The fluorescence
      displacement technique allows fast and precise monitoring of cell height and
      volume, thus providing a valuable tool for characterizing the three-dimensional
      behaviour of migrating cells.

PMID- 21964859
TI  - Calculation of chromophore excited state energy shifts in response to molecular
      dynamics of pigment-protein complexes.
AB  - The absorption and energy transfer properties of photosynthetic pigments are
      strongly influenced by their local environment or "site." Local electrostatic
      fields vary in time with protein and chromophore molecular movement and thus
      transiently influence the excited state transition properties of individual
      chromophores. Site-specific information is experimentally inaccessible in many
      light-harvesting pigment-proteins due to multiple chromophores with overlapping
      spectra. Full quantum mechanical calculations of each chromophores excited state
      properties are too computationally demanding to efficiently calculate the
      changing excitation energies along a molecular dynamics trajectory in a pigment
      protein complex. A simplified calculation of electrostatic interactions with each
      chromophores ground to excited state transition, the so-called charge density
      coupling (CDC) for site energy, CDC, has previously been developed to address
      this problem. We compared CDC to more rigorous quantum chemical calculations to
      determine its accuracy in computing excited state energy shifts and their
      fluctuations within a molecular dynamics simulation of the bacteriochlorophyll
      containing light-harvesting Fenna-Mathews-Olson (FMO) protein. In most cases CDC
      calculations differed from quantum mechanical (QM) calculations in predicting
      both excited state energy and its fluctuations. The discrepancies arose from the
      inability of CDC to account for the differing effects of charge on ground and
      excited state electron orbitals. Results of our study show that QM calculations
      are indispensible for site energy computations and the quantification of
      contributions from different parts of the system to the overall site energy
      shift. We suggest an extension of QM/MM methodology of site energy shift
      calculations capable of accounting for long-range electrostatic potential
      contributions from the whole system, including solvent and ions.

PMID- 21964860
TI  - Severe osteogenesis imperfecta caused by a small in-frame deletion in CRTAP.
AB  - Mutations of proteins involved in posttranslational modification of collagen type
      I can cause osteogenesis imperfecta (OI) inherited in a recessive pattern. The
      cartilage-associated protein (CRTAP) is part of a heterotrimeric complex
      (together with prolyl-3-hydroxylase-1 [P3H1] and cyclophilin B) that 3
      hydroxylates the alpha 1 chain of collagen type I at proline residue 986 and
      plays a collagen chaperon role. CRTAP mutations usually cause severe OI. We
      report on a patient with OI and a homozygous in-frame deletion in CRTAP and a
      severe form of OI. The girl was born with markedly deformed long bones. Despite
      intravenous bisphosphonate treatment, she developed multiple vertebral
      compression fractures and severe scoliosis and at 4 years of age was able to sit
      only with support. Although CRTAP transcript levels were normal in the patient's
      fibroblasts, protein levels of both CRTAP and P3H1 were severely reduced. The
      degree of 3-hydroxylation at proline residue 986 was also decreased. This report
      characterizes a patient with a CRTAP small in-frame deletion. We are unaware of
      prior reports of this finding. We suggest that this deletion affects crucial
      amino acids that are important for the interaction and/or stabilization of CRTAP
      and P3H1.

PMID- 21964861
TI  - Disseminated adenovirus disease in immunocompromised patient successfully treated
      with oral ribavirin: a case report.
AB  - In patients with immunological disorders, adenovirus infections are associated
      with significant rates of morbidity and mortality. Only few hematological units
      use molecular virological methods, such as polymerase chain reaction, for
      surveillance of adenovirus infection, and treatment strategies have never been
      evaluated in multicenter clinical trials. This report describes the detection and
      treatment of human adenovirus (HAdVs) disseminated disease in the case of a 46
      year-old immunocompromised female having myelodysplastic syndrome with refractory
      cytopenia with multilineage dysplasia: International Prognostic Scoring System 1.
      Serum and urine samples were tested for the presence of adenoviral DNA using the
      quantitative real-time polymerase chain reaction (PCR) assay. For additional
      confirmation, sequencing of PCR products was also performed. With real-time PCR,
      we detected HAdV DNA in both serum and urine samples. The viral level constantly
      decreased with applied oral ribavirin therapy. As the result of sequencing, HAdVs
      type 11 was determined. Surveillance of adenovirus by real-time PCR is useful in
      detecting and monitoring disseminated HAdV infection; it is a potential standard
      diagnostic approach that could assist clinicians to decide whether antiviral
      therapy ought to be administered.

PMID- 21964862
TI  - Angiogenesis in oral lichen planus: an in vivo and immunohistological evaluation.
AB  - Oral lichen planus (OLP) is an autoimmune disease with an inflammatory
      pathogenesis. The angiogenetic phenomenon is a mechanism at the base of the
      pathogenesis of chronic inflammatory processes. The aim of this research is to
      evaluate the angiogenetic phenomenon, comparing an in vitro method with an in
      vivo one. Thirty OLP patients and 30 healthy subjects were enrolled in the study.
      Immunohistochemical analysis of the vascular-endothelial growth factor (VEGF) and
      vascular-endothelial adhesion molecules were carried out by the means of primary
      antibodies and anti-CD34, anti-VEGF, anti-CD106 antigen (VCAM-1) and anti-CD54
      antigen (ICAM-1). Capillary density and others capillaroscopic parameters were
      tested in vivo using oral videocapillaroscopy. The results reveal the presence of
      a significant angiogenesis in OLP patients through the immunoexpression of VEGF,
      CD34, CD106 and CD54 (p < 0.001). Capillaroscopic analysis demonstrates
      significant value for the following parameters: density, tortuosity, loop
      diameter, afferent and efferent capillary loop diameter. The in vivo and in vitro
      investigation in OLP reveals a significant angiogenesis.

PMID- 21964863
TI  - The 5q- syndrome: biology and treatment.
AB  - OPINION STATEMENT: The 5q- syndrome is a myelodsyplastic syndrome (MDS)
      characterized by symptomatic anemia and an indolent natural history with low
      transformation potential. Our understanding of the molecular pathogenesis of this
      disease has advanced considerably, paralleled by the delineation of the relevant
      targets underlying selective lenalidomide sensitivity. The context in which one
      treats the 5q- syndrome, and all lower risk MDS, is critical. The focus of
      treatment should remain the amelioration of refractory cytopenias. In the 5q-
      syndrome, lenalidomide is the treatment of choice for patients with symptomatic
      anemia as it relieves the burden of transfusion dependence and iron overload in
      the majority of cases. We discuss herein the current understanding of the biology
      of the 5q- syndrome, actions of efficacy of lenalidomide and strategies for
      clinical management.

PMID- 21964864
TI  - Potential role of Hsp90 inhibitors in overcoming cisplatin resistance of bladder
      cancer-initiating cells.
AB  - For metastatic bladder cancer patients, systemic cisplatin (CDDP)-based
      combination chemotherapy is the first-line choice of treatment. Although up to
      70% of advanced bladder cancer patients initially show good tumor response to
      this form of combination chemotherapy, over 90% of good responders relapse and
      eventually die of the disease. According to the cancer stem cell theory, this
      phenomenon is attributable to the re-growth of bladder cancer-initiating cells
      (BCICs) that have survived chemotherapy. In this study, the authors have isolated
      BCICs from cultured human bladder cancer cells to analyze their sensitivity to
      CDDP and to investigate whether heat-shock protein 90 (Hsp90) inhibitors
      potentiate the cytotoxicity of CDDP on BCICs. First, the authors have confirmed
      that a CD44+ subpopulation of 5637 cells met the requirements to be considered
      tumor-initiating cells. These BCICs were more resistant to CDDP and exhibited
      more activity in the Akt and ERK oncogenic signaling pathways when compared with
      their CD44- counterparts. The Hsp90 inhibitor 17-(dimethylaminoethylamino)-17
      demethoxygeldanamycin (17-DMAG), which simultaneously inactivated both Akt and
      ERK signaling at noncytocidal concentrations, synergistically potentiated the
      cytotoxicity of CDDP against BCICs by enhancing CDDP-induced apoptosis in vitro.
      The potentiating effect of 17-DMAG was more effective than a combination of the
      two inhibitors specific for the Akt and ERK pathways. Finally, the authors have
      confirmed that, though human BCIC xenografts exhibited resistance to a single
      administration of CDDP and the Hsp90 inhibitor 17-(allylamino)-17
      demethoxygeldanamycin (17-AAG), 17-AAG sensitized them to CDDP in a mouse model.
      These data encourage clinical trials of Hsp90 inhibitors as they may improve
      therapeutic outcomes of CDDP-based combination chemotherapy against advanced
      bladder cancer.

PMID- 21964865
TI  - Liquid chromatography electrospray ionization tandem mass spectrometry for the
      detection of mesocarb abuse in horse doping.
AB  - A method is described for the determination of mesocarb abuse in equestrian sport
      by combining gradient liquid chromatography and electrospray ionization tandem
      mass spectrometry. Mesocarb was administrated orally to two horses at a dose of
      50 ug/kg. Urine samples were collected up to 120 h post administration.
      Hydrolyzed and conjugated urine fractions were handled using liquid-liquid
      extraction (LLE). The identity of the parent drug and metabolites was confirmed
      using liquid chromatography combined with tandem mass spectrometry (MS/MS).
      Mesocarb and seven metabolites were detected in horse urine. Mono- and two di
      hydroxylated metabolites were the main metabolites observed in horse urine
      samples. Based on the differences in MS/MS spectra it was supposed that these
      metabolites were been formed by the hydroxylation of the phenylisopropyl moiety
      of mesocarb whilst the main process of hydroxylation of mesocarb in human
      occurred in the phenylcarbamoyl moiety. The main metabolites were almost
      completely glucuroconjugated. Minor metabolites such as p-hydroxymesocarb and
      three di-hydroxylated metabolites together with parent mesocarb were also
      presented in the free urine fraction. This study has shown that two mono- and two
      di-hydroxylated metabolites are useful for controlling the abuse of mesocarb in
      horses.

PMID- 21964866
TI  - Three-year comparison of subcutaneous insulin pump treatment with multi-daily
      injections on HbA1c, its variability and hospital burden of children with type 1
      diabetes.
AB  - Treatment with continuous subcutaneous insulin infusion (CSII) allows a large
      degree of treatment individualization and intensification in children with
      diabetes. The study's aim was to evaluate the impact of treatment with CSII on
      glycated haemoglobin level (HbA1c) in children with diabetes and investigate
      whether introduction of CSII is associated with an increased risk of acute
      complications of diabetes. Patients treated throughout the recruitment period
      exclusively with multiple daily injections (MDI) were matched for duration of
      diabetes and HbA1c level at baseline with patients treated exclusively with CSII
      in a 1:1 group ratio (n = 223 and 231 for MDI and CSII, respectively). The CSII
      group showed lower HbA1c after the observation period (7.98 +/- 1.38 vs. 7.56 +/-
      0.97; P = 0.002). HbA1c variability measured as standard deviations of average
      values was also lower in the CSII group (0.73 +/- 0.45 vs. 0.84 +/- 0.54; P =
      0.049). The rate of hospitalization due to acute events was similar in both
      groups (14.7/100 vs. 14.0/100 person/years in the MDI and CSII group, P = 0.72).
      Duration of hospital stay per year was on average 1.25 days shorter in the CSII
      group (P = 0.0004), but the risk of acute complications resulting in
      hospitalization did not differ between the groups (hazard ratio (HR) 1.16; 95%
      confidence interval (95% CI) 0.68-1.63). The most significant risk factor for
      hospitalization due to acute complications was baseline HbA1c concentration (HR
      1.25; 95% CI 1.14-1.37). In conclusion, CSII treatment may improve glycemic
      control and reduce its variability. Change of MDI to CSII does not alter the risk
      of hospitalization and may reduce the annual duration of hospitalization in
      children with diabetes.

PMID- 21964867
TI  - Task-related variations in the surface EMG of the human first dorsal interosseous
      muscle.
AB  - Evidence from human and animal studies suggests that motor neuron pool
      organization is not uniform for all motor tasks. Groupings of motor units within
      a muscle may be recruited differentially for a given task based on principles
      beyond anatomical or architectural features of the muscle alone. This study aimed
      to determine whether: (1) there was differential activation across locations of
      the first dorsal interosseous (FDI) muscle during a given task, (2) the
      differential activation was related to directional requirements and/or end goal
      of the task, and (3) there was an anatomical pattern to the differential
      activation. Twenty-six healthy right-handed participants carried out isometric
      finger/hand contractions in sitting while surface EMG was collected from 4
      bipolar sites on the FDI muscle simultaneously. The tasks included: abduction,
      flexion, diagonal, 30% abduction + 30% flexion, 30% flexion + 30% abduction, key
      pinch, and power grasp. Mean peak integrated EMG for each task was normalized to
      site and task specific mean M waves. Differential activation was evident across
      FDI sites based on movement direction, order of directional components within a
      combination condition, and end goal of the task. There was greatest activation in
      the distal ulnar site for all tasks. Additionally there was a trend toward an
      ordering effect in the amount of activation at each site: distal ulnar > distal
      radial > proximal radial > proximal ulnar.

PMID- 21964868
TI  - Excitability changes induced in the human auditory cortex by transcranial direct
      current stimulation: direct electrophysiological evidence.
AB  - Transcranial direct current stimulation (tDCS) can systematically modify behavior
      by inducing changes in the underlying brain function. Objective
      electrophysiological evidence for tDCS-induced excitability changes has been
      demonstrated for the visual and somatosensory cortex, while evidence for
      excitability changes in the auditory cortex is lacking. In the present study, we
      applied tDCS over the left temporal as well as the left temporo-parietal cortex
      and investigated tDCS-induced effects on auditory evoked potentials after anodal,
      cathodal, and sham stimulation. Results show that anodal and cathodal tDCS can
      modify auditory cortex reactivity. Moreover, auditory evoked potentials were
      differentially modulated as a function of site of stimulation. While anodal tDCS
      over the temporal cortex increased auditory P50 amplitudes, cathodal tDCS over
      the temporo-parietal cortex induced larger N1 amplitudes. The results directly
      demonstrate excitability changes in the auditory cortex induced by active tDCS
      over the temporal and temporo-parietal cortex and might contribute to the
      understanding of mechanisms involved in the successful treatment of auditory
      disorders like tinnitus via tDCS.

PMID- 21964870
TI  - Seasonal AVS-SEM relationship in sediments and potential bioavailability of
      metals in industrialized estuary, southeastern Brazil.
AB  - In anoxic sediments, as those found in estuaries, the mobility of metals can be
      controlled by the formation of stable sulfide complexes. The potential
      bioavailability of a metal can then be predicted on the basis of the acid
      volatile sulfide (AVS) and simultaneously extracted metals (SEM) criterion.
      Distributions of AVS and SEM (Hg, Cu, Pb, Cd, Zn, and Ni) along the sediment
      profiles were determined seasonally for three rivers that constitute the Santos
      Cubatao estuarine system (SE Brazil), which is located in one of the most
      industrialized areas of Latin America. AVS and SEM concentrations varied
      significantly, from 0.04 to 31.9 MUmol g(-1) and 0.086-6.659 MUmol g(-1),
      respectively. The highest AVS levels in sediments were detected in the winter,
      whereas high SEM values predominated in the summer. Considering SEM-AVS molar
      differences as a parameter to evaluate potential bioavailability, sediments
      nearest to the industrial area represent higher risk to biota, especially during
      the summer. It is due to relatively low AVS values and not necessarily high
      concentrations of metals.

PMID- 21964871
TI  - A review of the effects of memantine on clinical progression in Alzheimer's
      disease.
AB  - BACKGROUND: As Alzheimer's disease (AD) progresses, patients become increasingly
      dependent on others, placing a substantial impact on the daily lives of patients
      and caregivers. A treatment that slows clinical progression is a realistic and
      meaningful therapeutic goal for patients and caregivers. If given early, such a
      treatment would be expected to maximise any potential benefit. Memantine has
      shown clinical benefits in the key domains of AD, both as monotherapy and in
      combination with a cholinesterase inhibitor (ChEI). METHODS: Memantine now has a
      considerable database of published studies and is associated with benefits in
      aspects of behaviour, cognition and communication, and on clinical progression.
      The results of these clinical studies are reviewed. RESULTS: Short-term clinical
      studies (<=28 weeks) have shown that memantine reduces clinical worsening and has
      also demonstrated positive effects in aspects of cognition--language, memory,
      praxis, functional communication--and in activities of daily living. Furthermore,
      memantine has been shown to reduce the rate of emergence of troublesome behaviour
      in patients with AD who were asymptomatic at baseline. Long-term follow-up
      studies (>1 year) have shown that the benefits of memantine are sustained and
      increase over time, and that memantine can delay nursing home placement in
      patients with AD. CONCLUSIONS: These findings provide evidence for the benefits
      of memantine, either alone or in combination with a ChEI, in slowing clinical
      progression in AD, and indicate that early treatment initiation may maximise
      clinical success. The benefits of memantine increase over time, allowing patients
      to remain independent for longer, alleviating caregiver burden and delaying
      institutionalisation.

PMID- 21964873
TI  - Determination of ofloxacin using a highly selective photo probe based on the
      enhancement of the luminescence intensity of Eu3+--ofloxacin complex in
      pharmaceutical and serum samples.
AB  - A rapid, simple and sensitive spectrofluorimetric method for determination of
      trace amount of ofloxacin was developed. At pH 5.1 the ofloxacin enhances the
      luminescence intensity of the Eu(3+) ion in Eu(3+)- ofloxacin complex at
      lambda(ex) = 365 nm. The produced luminescence intensity of Eu(3+)-ofloxacin
      complex was in proportional to the concentration of ofloxacin. The working range
      for the determination of ofloxacin was 5.0 * 10(-9)-5.0 * 10(-6) mol L(-1) with
      lower detection limit (LOD) and quantitative detection limit (QDL) of 3 * 10(-9)
      and 9 * 10(-9) mol L(-1), respectively. The enhancement mechanism of the
      luminescence intensity in the Eu(3+)-ofloxacin system has been also explained.
      The method revealed good selectivity for ofloxacin in the presence of coexisting
      substances and used successfully for the assay of ofloxacin in pharmaceutical
      preparations and serum. A comparison with other standard methods was also
      discussed.

PMID- 21964874
TI  - A new piezochromic fluorescence and aggregation-induced emission compound
      containing tetraphenylethylene and triphenylamine moieties with morphology
      alterable property.
AB  - A novel piezochromic fluorescent (PCF) compound with aggregation-induced emission
      (AIE) effect and morphology-alterable emission property was developed. The
      amorphous and crystalline aggregates were obtained, and their spectroscopic
      properties and morphological structures were reversibly and repeatedly exhibited
      upon pressing (fuming) or annealing. The piezochromic fluorescent nature was
      generated through crystalline-amorphous phase transformation. It was proposed
      that AIE compounds existing a twisted propeller-shaped conformation will exhibit
      PCF activity. The common relationship betweeen AIE and PCF established will guide
      researchers in identifying and synthesizing more piezochromic fluorescent
      materials.

PMID- 21964875
TI  - Anti-proliferative effect of Melissa officinalis on human colon cancer cell line.
AB  - Melissa officinalis L. (Lamiaceae) is consumed as a traditional herbal tea in the
      Mediterranean region. The cytotoxic effect of the 50% ethanolic and aqueous
      extract, determined by the MTT and NR assays, was evaluated in vitro on Human
      Colon Cancer Cell Line (HCT-116), using Triton 10% as positive control. The 50%
      ethanolic extract showed significant differences after 72 h of treatment,
      reducing cell proliferation to values close to 40%, even the lowest dose tested
      (5 MUg/ml). In the MTT assay, the same extract caused the lowest cell viability
      with 13% at a concentration of 1,000 MUg/ml after 72 h of treatment, being a
      value lower than Triton 10%. The antioxidant activity was also confirmed
      evaluating the capacity of the extracts to scavenge ABTS and DPPH radicals, and
      IC(50) values were highly correlated with the total phenolic and flavonoid
      content. Bioassay guided fractionation led to the isolation of an anti
      proliferative compound, rosmarinic acid. Its structural elucidation was performed
      by HPLC/DAD/ESI/MS analysis. High dose of rosmarinic acid (1,000 MUg/ml) was
      clearly cytotoxic against HCT-116 cells, with a significant decrease in cell
      number since the earliest time point (24 h).

PMID- 21964876
TI  - Kinetics of the inhibition of renin and angiotensin i converting enzyme by polar
      and non-polar polyphenolic extracts of Vernonia amygdalina and Gongronema
      latifolium leaves.
AB  - The aim of this study was to determine the in vitro modulation of the renin
      angiotensin system by polyphenolic extracts and fractions of two green leafy
      vegetables, Vernonia amygdalina (VA) and Gongronema latifolium (GL), that are
      used for food and medicinal purposes. An 80% acetone extract of each leaf was
      fractionated on silicic acid-packed column to give two main fractions: acetone
      eluate (flow-through) and ethanol eluate (column-bound), that consist mostly of
      chlorophyllic and non-chlorophyllic fractions, respectively. Column fractionation
      resulted in polyphenolic fractions that displayed higher potency against
      angiotensin converting enzyme (ACE) and renin than the crude acetone extracts;
      generally, the chlorophyllic fraction was more active than the non-chlorophyllic
      fraction. ACE-inhibitory activity was significantly higher (p < 0.05) for the
      chlorophyllic fraction of VA than GL, with IC(50) values of 0.207 and 0.413
      mg/ml, respectively. Similarly, the chlorophyllic fraction of VA had
      significantly higher (p < 0.05) renin inhibition than GL, with IC(50) values of
      0.172 and 0.513 mg/ml, respectively. Kinetics studies showed that the
      chlorophyllic fractions of VA and GL exhibited mostly mixed-type ACE and renin
      inhibitions. We concluded that the hydrophobic nature of the chlorophyllic
      fraction may have contributed to the increased interaction with enzyme protein
      and inhibition of activities of ACE and renin.

PMID- 21964877
TI  - Positive effects of astaxanthin on lipid profiles and oxidative stress in
      overweight subjects.
AB  - Astaxanthin, a carotenoid, has antioxidant activity as well as many positive
      effects, such as anticancer and anti-inflammatory effects. We performed a
      randomized, double-blind, placebo-controlled study to investigate the effects of
      astaxanthin on lipid profiles and oxidative stress in overweight and obese adults
      in Korea. In total, 27 subjects with body mass index >25.0 kg/m(2) were enrolled
      and randomly assigned into two groups administered astaxanthin or placebo
      capsules for 12 weeks. Total cholesterol, triglycerides, high density lipoprotein
      (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, apolipoprotein A1
      (ApoA1), and apolipoprotein B (ApoB) were measured before and after intervention.
      Malondialdehyde (MDA), isoprostane (ISP), superoxide dismutase (SOD), and total
      antioxidant capacity (TAC), as oxidative stress biomarkers, were measured at
      baseline and at 4, 8, and 12 weeks after intervention. LDL cholesterol and ApoB
      were significantly lower after treatment with astaxanthin, compared with the
      start of administration, whereas none of the lipid profiles was changed in the
      placebo group. At the baseline, all four biomarkers were not significantly
      different between the two groups. Compared with the placebo group, MDA and ISP
      were significantly lower, but TAC was significantly higher in the astaxanthin
      group at 12 weeks. These results suggest that supplementary astaxanthin has
      positive effects by improving the LDL cholesterol, ApoB, and oxidative stress
      biomarkers.

PMID- 21964878
TI  - Quality of life in elderly patients with essential thrombocythaemia. An Italian
      multicentre study.
AB  - Essential thrombocythaemia (ET) is a myeloproliferative neoplasm characterized by
      elevated platelet counts and increased incidence of thrombosis and haemorrhage.
      Median age at diagnosis is 65-70 years. Life expectancy is similar to that of the
      healthy population. Symptoms and complications may affect quality of life (QoL);
      in particular, in elderly patients ET may represent an additional burden. We
      performed a survey in 494 elderly ET patients to evaluate patient-reported
      outcomes (PROs). Comorbidities were present in 305 (62%) patients. Factorial
      analysis based on survey items representing psychological aspects of daily life
      identified an "attitude domain" with four clusters of patients: (A) very
      pessimistic (n = 99), (B) pessimistic (n = 101), (C) optimistic (n = 90), and (D)
      very optimistic (n = 107). Patients in cluster A had more comorbidities (p =
      0.003) while patients in cluster D required fewer medical visits and were less
      disturbed by medications (p < 0.0001). Independent factors predicting Short-Form
      Health Survey, version 2 physical QoL were grade of optimism (p < 0.0001), gender
      (p = 0.007), and Charlson comorbidity index (p < 0.0001)). Grade of optimism and
      disturbances related to medication predicted mental QOL (p < 0.0001). In
      conclusion, physicians should take into consideration PROs, as "attitude" is
      associated with physical and mental QoL. Treatment should be tailored to
      patients' needs according to comorbidities, lifestyle, and psychological
      conditions.

PMID- 21964879
TI  - Vici syndrome--a rapidly progressive neurodegenerative disorder with
      hypopigmentation, immunodeficiency and myopathic changes on muscle biopsy.
AB  - Since its first description by Vici et al. [1988], further reports have continued
      to broaden the clinical phenotype of this rare multisystem disorder. Main
      features of agenesis of corpus callosum (ACC), hypopigmentation,
      immunodeficiency/recurrent infections, cataracts, severe failure to thrive, and
      profound psychomotor delay have been reported in all cases. An additional feature
      is the recent evidence for neuromuscular involvement. We describe a female infant
      with the above core features in whom an initial rapid neurological deterioration
      and associated transient left ventricular hypertrophy and liver dysfunction was
      followed by relative clinical stability after ten months of age. This case
      further underlines the clinical phenotype of Vici syndrome as an early onset
      neurodegenerative disorder with hypopimentation, recurrent infections and muscle
      findings indicating myopathic and neurogenic features.

PMID- 21964880
TI  - Acute effects of mechanical shocks on finger blood flow: influence of shock
      repetition rate and shock magnitude.
AB  - OBJECTIVES: Finger blood flow is reduced by hand-transmitted vibration but there
      has been little study of the peripheral vascular response to repetitive
      mechanical shocks. This study investigated how reductions in finger blood flow
      depend on shock repetition rate and the peak and rms magnitude of acceleration.
      METHODS: Subjects attended seven sessions: six with repetitive mechanical shocks
      and a control session with no shocks. Each session comprised five successive 5
      min periods: (1) no force and no vibration, (2) force and no vibration, (3) force
      and vibration, (4) force and no vibration and (5) no force and no vibration.
      During the second-fourth periods, the palm of the right hand applied 2-N force to
      a vibrator. During the third period, a 125-Hz mechanical shock was applied with
      one of four repetition rates (1.3, 5.3, 21 or 83.3/s) and one of three
      acceleration magnitudes (2.5, 5 or 10 ms(-2) rms, unweighted). Finger blood flow
      was measured every 30 s in the middle and little fingers of the right (exposed)
      hand and the left (unexposed) hand. RESULTS: Different repetition rates (1.3-83.3
      s(-1)) and different peak magnitudes (10-88 ms(-2) peak) but the same rms
      acceleration (10 ms(-2) rms) caused similar decreases in blood flow in fingers on
      exposed and unexposed hands. Shocks with a 83.3 s(-1) repetition rate, peak
      magnitude of 10 ms(-2) and rms acceleration of 10 ms(-2) provoked greater
      reduction in finger blood flow than shocks with the same peak magnitude but lower
      repetition rate (21 or 5.3 s(-1)) and lower rms acceleration (5 or 2.5 ms(-2)).
      CONCLUSIONS: For shocks similar to those based on 125-Hz oscillations with
      repetition rates between 1.3 and 83.3 s(-1), acute reductions in finger blood
      flow can be predicted from the rms acceleration.

PMID- 21964882
TI  - Improvement of sodium status to optimize the efficacy of Renin-Angiotensin system
      blockade.
AB  - Blockade of the renin-angiotensin-aldosterone system (RAAS) offers superior
      renoprotection in the treatment of patients with hypertension, but the efficacy
      of RAAS inhibition strongly depends on sodium status, presumably in relation to
      extracellular volume status. Because assessing volume status by physical
      examination is challenging, 24-hour urine collection and NT-proBNP levels are
      useful tools for guiding volume management and achieving sodium status targets.

PMID- 21964881
TI  - The cardinal role of the phospholipase A(2)/cyclooxygenase-2/prostaglandin E
      synthase/prostaglandin E(2) (PCPP) axis in inflammostasis.
AB  - The process of inflammation is regulated in part by bioactive lipids of which
      prostaglandins/eicosanoids form an important class. We provide evidence that the
      phospholipase A(2)/cyclooxygenase-2/prostaglandin E synthase/prostaglandin E(2)
      (PCPP) axis is positioned at the core of a natural regulatory circuit controlling
      the initiation, magnitude, duration, and resolution of the inflammatory response.
      During the inflammatory phase, proinflammatory cytokine, chemokine and matrix
      destructive metalloprotease expression levels are moderated by the PCPP axis
      through the modulation of signaling pathways that control proinflammatory gene
      expression at transcriptional, post-transcriptional, and translational levels.
      The PCPP axis also contributes to the activation of lipid mediator class
      switching; this highly coordinated process results in the biosynthesis of
      lipoxins and resolvins that promote inflammatory resolution through a variety of
      cellular and molecular mechanisms. The PCPP axis activity is autoregulated by way
      of a positive feedback circuit involving PGE(2)-mediated, p38 MAPK-dependent
      stabilization of COX-2 mRNA and COX-2 catalytic potentiation via its limited
      proteolytic cleavage (e.g., Ca(2+)-activated calpains). In conclusion, through
      its fine temporal modulation of multiple signaling cassettes via EP1-EP4 GPCRs,
      PGE(2) influences the onset, course, magnitude, and duration of the inflammatory
      response and functions as a key feedback regulator of the cellular and molecular
      processes controlling inflammation.

PMID- 21964883
TI  - Lysophosphatidic acid receptor 2/3-mediated IL-8-dependent angiogenesis in
      cervical cancer cells.
AB  - The expression of lysophosphatidic acid (LPA)-specific receptors in cervical
      cancer has not been clearly defined. In this study, we identified LPA1, LPA2 and
      LPA3 receptors' mRNA in SiHa, HeLa and CaSki cell lines by RT-PCR. These
      receptors were not associated with tumor cell proliferation in vitro. We then
      used a xenograph animal model to evaluate the effects of these receptors on in
      vivo cervical cancer tumorigenicity. When SiHa cells with different receptor
      expression patterns were seeded on the backs of SCID mice, the resulting knockout
      of both LPA2 and LPA3 significantly attenuated tumor growth; this decrease in
      tumor growth was found to be linked with decreased angiogenesis (microvessel
      density), suggesting that LPA2 and LPA3 are crucial for in vivo tumor growth
      through an angiogenic mechanism. We further investigated this mechanism of LPA
      receptor 2/3-mediated angiogenic capability by analyzing angiogenic factors in
      protein lysates from receptor knockout tumors, by detecting interleukin (IL-8)
      mRNA expression after treating with siRNA, by evaluating the biological role of
      LPA-enhanced IL-8 via endothelial cell tube formation, monolayer permeability,
      migration and cell growth assays, and by IL-8 knockout xenograft mice modeling.
      We found that the angiogenesis is mediated through IL-8. Finally, we evaluated
      the regulation pathways involved in LPA-induced IL-8 expression. We found that
      LPA receptor 2/3-mediated IL-8 expression occurs through Gi/PI3K/AKT, Gi/PKC and
      IkappaB/NF-kappaB signaling. In conclusion, we propose that LPA2 and LPA3 might
      play an important role in cervical cancer tumor growth through IL-8-dependent
      angiogenesis.

PMID- 21964885
TI  - Assessment of HbA1c as a diagnostic tool in diabetes and prediabetes.
AB  - To evaluate HbA1c as a diagnostic tool in prediabetes-impaired fasting glucose
      (IFG) and impaired glucose tolerance (IGT), and newly detected diabetes (NDD),
      defined by plasma glucose and OGTT. 2,231 subjects, of mean age 50.3 +/- 13.9
      years and mean BMI 29.5 +/- 6.2 kg/m(2), underwent an OGTT. HbA1c performance was
      assessed using the area under the receiver operating characteristics curve (AUC
      ROC). HbA1c was significantly higher in all groups with altered glucose tolerance
      5.72 +/- 0.61% in IFG, 5.84 +/- 0.63% in IGT, and 7.5 +/- 1.69% in NDD when
      compared to normal glucose tolerance-5.23 +/- 0.65% (P < 0.0001). HbA1c of both
      prediabetic groups was significantly lower in comparison with NDD (P < 0.0001);
      in IGT being significantly higher than in IFG (P = 0.02). ROC analysis
      demonstrated good performance of HbA1c for diagnosing diabetes-AUC-ROC 0.958 (95%
      CI: 0.946-0.970), as well as prediabetes-AUC-ROC 0.729 (95% CI: 0.702-0.755). The
      optimal cut-off level of HbA1c for diagnosing diabetes was 6.1% (sensitivity 86%,
      specificity 92%) and for undiagnosed prediabetes-5.5% (sensitivity 71%,
      specificity 64%). HbA(1c) appears to be a useful, convenient, and reliable tool
      for identifying subjects with prediabetes and diabetes and should be considered
      in the development of diagnostic strategies.

PMID- 21964886
TI  - Voltammetric determination of glutathione in haemolysed erythrocyte and tablet
      samples using modified-multiwall carbon nanotubes paste electrode.
AB  - A chemically modified electrode was prepared by incorporating p-aminophenol into
      multiwall carbon nanotubes paste matrix. Cyclic voltammetry, square wave
      voltammetry, double potential step chronoamperometry, and electrochemical
      impedance spectroscopy were used to investigate the electrochemical behaviour of
      glutathione at the chemically modified electrode prepared. According to the
      results, p-aminophenol multiwall carbon nanotubes paste electrode (p-APMWCNTPE)
      showed high electrocatalytic activity for glutathione oxidation, producing a
      sharp oxidation peak current at about +0.285 vs Ag/AgCl reference electrode at pH
      5.0. Chronoamperometry was also used to determine glutathione's catalytic rate
      constant and diffusion coefficient at p-APMWCNTPE. The square wave voltammetric
      peak current of glutathione increased linearly with glutathione concentration in
      the range of 2.0 * 10(-7) - 1.0 * 10(-4) mol L(-1) with a detection limit of 9.0
      * 10(-8) mol L(-1). The method was also successfully employed as a selective,
      simple, and precise method for the determination of glutathione in haemolysed
      erythrocyte, tablet, and urine samples.

PMID- 21964887
TI  - Using Alba EmotingTM to work with emotions in psychotherapy.
AB  - Alba EmotingTM is a physical method to help recognize, induce, express and
      regulate the basic emotions. This is achieved through specific breathing,
      postural and facial behaviours. Alba Emoting is based on psychophysiological
      research by Susana Bloch and her collaborators, who have applied this method
      mainly to train actors. Alba Emoting can be used in psychotherapy to facilitate
      emotion awareness, regulation and transformation. It can also help therapists
      better recognize their own and their clients' emotions. The application of Alba
      Emoting in psychotherapy is illustrated with a case example. KEY PRACTITIONER
      MESSAGE: Alba Emoting is a physical, scientific method for working with emotions.
      Alba Emoting can help therapists better recognize their own and their clients'
      emotions. Alba Emoting can help clients achieve better emotional awareness and
      regulation. Alba Emoting can also help clients experience and express emotions
      they may normally inhibit.

PMID- 21964884
TI  - Gut microbiota and diabetes: from pathogenesis to therapeutic perspective.
AB  - More than several hundreds of millions of people will be diabetic and obese over
      the next decades in front of which the actual therapeutic approaches aim at
      treating the consequences rather than causes of the impaired metabolism. This
      strategy is not efficient and new paradigms should be found. The wide analysis of
      the genome cannot predict or explain more than 10-20% of the disease, whereas
      changes in feeding and social behavior have certainly a major impact. However,
      the molecular mechanisms linking environmental factors and genetic susceptibility
      were so far not envisioned until the recent discovery of a hidden source of
      genomic diversity, i.e., the metagenome. More than 3 million genes from several
      hundreds of species constitute our intestinal microbiome. First key experiments
      have demonstrated that this biome can by itself transfer metabolic disease. The
      mechanisms are unknown but could be involved in the modulation of energy
      harvesting capacity by the host as well as the low-grade inflammation and the
      corresponding immune response on adipose tissue plasticity, hepatic steatosis,
      insulin resistance and even the secondary cardiovascular events. Secreted
      bacterial factors reach the circulating blood, and even full bacteria from
      intestinal microbiota can reach tissues where inflammation is triggered. The last
      5 years have demonstrated that intestinal microbiota, at its molecular level, is
      a causal factor early in the development of the diseases. Nonetheless, much more
      need to be uncovered in order to identify first, new predictive biomarkers so
      that preventive strategies based on pre- and probiotics, and second, new
      therapeutic strategies against the cause rather than the consequence of
      hyperglycemia and body weight gain.

PMID- 21964888
TI  - Oncological superiority of hilar en bloc resection for the treatment of hilar
      cholangiocarcinoma.
AB  - PURPOSE: Long-term results after liver resection for hilar cholangiocarcinoma are
      still not satisfactory. Previously, we described a survival advantage of patients
      who undergo combined right trisectionectomy and portal vein resection, a
      procedure termed "hilar en bloc resection." The present study was conducted to
      analyze its oncological effectiveness compared to conventional hepatectomy.
      PATIENTS: During hilar en bloc resection, the extrahepatic bile ducts were
      resected en bloc with the portal vein bifurcation, the right hepatic artery, and
      liver segments 1 and 4 to 8. With this "no-touch" technique, preparation of the
      hilar vessels in the vicinity of the tumor was avoided. The long-term outcome of
      50 consecutive patients who underwent curative (R0) hilar en bloc resection
      between 1990 and 2004 was compared to that of 50 consecutive patients who
      received curative conventional major hepatectomy for hilar cholangiocarcinoma
      (perioperative deaths excluded). RESULTS: The 1-, 3-, and 5-year survival rates
      after hilar en bloc resection were 87%, 70%, and 58%, respectively, which was
      significantly higher than after conventional major hepatectomy. In the latter
      group, 1-, 3-, and 5-year survival rates were 79%, 40%, and 29%, respectively (P
      = 0.021). Tumor characteristics were comparable in both groups. A high number of
      pT3 and pT4 tumors and patients with positive regional lymph nodes were present
      in both groups. Multivariate analysis identified hilar en bloc resection as an
      independent prognostic factor for long-term survival (P = 0.036). CONCLUSIONS: In
      patients with central bile duct carcinomas, hilar en bloc resection is
      oncologically superior to conventional major hepatectomy, providing a chance of
      long-term survival even in advanced tumors.

PMID- 21964889
TI  - Additive lymph node dissection may be necessary in minute submucosal cancer of
      the stomach after endoscopic resection.
AB  - PURPOSE: In early gastric cancer (EGC), minute submucosal (SM1) invasion of the
      stomach has been regarded as an expanded indication for endoscopic resection
      (ER). The exact prediction of SM1 invasion before ER may be difficult. Thus, SM1
      invasion may be important to decide additive treatment after ER. This study was
      designed to investigate the incidence of lymph node metastasis (LNM) in SM1-EGC
      based on surgical specimens and to evaluate the factors that indicate additional
      treatment after ER. METHODS: From May 2005 to December 2008, 1,676 patients with
      EGC underwent surgery at Severance and Gangnam Severance Hospital, Seoul, Korea.
      Among them, 126 patients were diagnosed with differentiated SM1-EGC. The
      clinicopathologic characteristics were analyzed with respect to LNM and
      lymphovascular invasion (LVI), which is a known independent risk factor for LNM.
      Intratumoral marker immunohistochemistry was examined as a predictor of LVI.
      RESULTS: The mean SM1 invasion depth was 621.3 +/- 745.6 MUm. The LNM rates did
      not differ significantly between differentiated SM1-EGC (6.3%) and SM1-EGC (4.1%)
      meeting the expanded indication for ER. Female gender, moderate differentiation,
      LVI, and LVI grade were positively correlated with LNM. Female gender and
      elevated lesion morphology were associated with LVI. The expression levels of
      VEGF-C and OPHN1 were higher in LVI-positive tissues. CONCLUSIONS: The LNM rate
      in differentiated SM1-EGC meeting the expanded ER criteria was 4.1% in the
      present study, indicating that additional lymph node dissection may be necessary
      after ER in some cases of SM1-EGC.

PMID- 21964891
TI  - [Special edition gastrointestinal oncology 2011].

PMID- 21964890
TI  - Modulation of cortical motor networks following primed theta burst transcranial
      magnetic stimulation.
AB  - To investigate whether priming stimulation influences the responses of
      intracortical inhibitory and facilitatory motor circuits to a subsequent
      plasticity-inducing inhibitory theta burst TMS paradigm. Using standard
      transcranial magnetic stimulation (TMS) procedures, MEP amplitude, short-interval
      intracortical inhibition (SICI), and short-interval intracortical facilitation
      (SICF) were assessed at baseline and 5, 20 and 30 min following continuous theta
      burst stimulation (cTBS), intermittent TBS (iTBS), and iTBS-primed cTBS. SICI was
      assessed using paired-pulse TMS at inter-stimulus intervals (ISI) of 3 ms
      (SICI(3)) and the latency corresponding to the latency at which SICF was minimal
      in each individual. SICF was assessed at ISIs corresponding to Peak 1, Trough 1,
      Peak 2, and Peak 3 of each individual's SICF curve. When applied alone cTBS
      inhibited and iTBS facilitated MEP amplitudes. iTBS-primed cTBS resulted in
      greater MEP inhibition than cTBS alone. There were no changes in SICF and only
      marginal changes in SICI following any intervention. Synapses mediating MEP
      generation undergo modification following iTBS-primed cTBS, possibly through
      mechanisms related to metaplasticity or synaptic depotentiation. A lack of
      substantial changes in SICI and SICF under all experimental conditions suggests
      that the tested rTMS paradigms may be non-optimal for inducing robust modulation
      of the neural elements mediating SICI and SICF across subjects. Priming
      stimulation may provide an approach which facilitate neuroplastic change within
      the human motor cortex at least in circuits responsible for MEP generation.

PMID- 21964892
TI  - [Gastrointestinal oncology: from AGO to AGiO, ESDO and IDCA]].

PMID- 21964893
TI  - Biomarkers of anti-angiogenic therapy in metastatic colorectal cancer (mCRC):
      original data and review of the literature.
AB  - INTRODUCTION: Tumour angiogenesis via vascular endothelial growth factor (VEGF)
      is essential for promoting tumour progression and is overexpressed in colorectal
      cancer. The humanised monoclonal anti-VEGF antibody bevacizumab (Avastin(r),
      Genentech Inc., South San Francisco, CA) has shown activity in metastatic
      colorectal cancer (mCRC) combined with conventional chemotherapy. The search for
      biomarkers to predict response to anti-angiogenic therapy in mCRC is of great
      interest. We investigated several potential predictive anti-angiogenic markers
      including circulating endothelial progenitor cells (EPC) in patients with mCRC
      receiving bevacizumab containing treatment within a randomised multicenter phase
      2 study of the German AIO GI tumour study group. METHODS: We collected sequential
      blood samples and tumour tissues from patients participating in a clinical trial
      for patients with mCRC. We performed flow cytometry of mononuclear cells isolated
      from peripheral blood to assess CD 133 + or CD 34 + /KDR + EPC before the first
      bevacizumab containing chemotherapy and after 21 days. Circulating VEGF blood
      levels before a bevacizumab containing chemotherapy regimen and after 21 days and
      VEGF expression in tumour tissue were examined. RESULTS: Patients with mCRC and a
      partial remission after six months of immuno-chemotherapy containing bevacizumab
      showed a reduction of CD 34 negative KDR positive cells as early as 3 weeks after
      start of therapy. In contrast, no remarkable change in the number of CD 34 /KDR
      positive or CD 34 /CD133 positive cells was seen. Furthermore, there was no
      correlation between treatment response and VEGF expression within the tumour
      tissue. The mAb bevacizumab reduced serum-VEGF levels in patients independent of
      their treatment response to bevacizumab. DISCUSSION: We examined circulating
      endothelial progenitor cells (EPC), serum-VEGF levels and the tumour tissue VEGF
      expression of patients with mCRC under a bevacizumab containing chemotherapy. The
      patients with a partial remission after six months of immuno-chemotherapy showed
      a reduction of CD 34 negative KDR positive cells as early as 3 weeks after start
      of therapy. Neither serum nor tissue markers were of significant predictive value
      in our pilot study. Furthermore, we review the current data on biomarkers for
      anti-angiogenic therapy of mCRC.

PMID- 21964894
TI  - [Chemotherapy-associated steatohepatitis in patients with colorectal cancer and
      surgery on hepatic metastasis: clinical validation of a histopathological scoring
      system and preoperative risk assessment].
AB  - Colorectal cancer (CRC) can only be cured by complete resection of the tumour.
      Primarily unresectable metastases of the liver are treated by chemotherapy to
      achieve down-sizing of metastasis and curative resection. Chemotherapy can affect
      tumour-free healthy liver tissue and lead to histopathological and functional
      changes summarised as "chemotherapy-associated steatohepatitis" (CASH). We have
      evaluated a histopathological scoring system for CASH and searched for
      preoperative risk factors for the development of CASH. Liver alterations such as
      CASH were more pronounced when patients received chemotherapy, especially when
      treated with oxaliplatin. A higher BMI, male sex and elevated serum transaminases
      were risk factors for the development of CASH. Patients with a higher CASH score,
      reflecting more advanced changes in liver tissue, had a higher serum peak
      bilirubin level postoperatively. We did not find a higher morbidity or mortality
      in patients with a more severe liver damage measured by the CASH score.

PMID- 21964895
TI  - [Gangliocytic paraganglioma--a rare differential diagnosis of a submucosal
      duodenal tumor].
AB  - We report on the case of a 36-year-old male patient who was found to have a
      submucosal duodenal tumour during the diagnostic work-up of gastrointestinal
      bleeding. After exclusion of other tumour manifestations complete endoscopic
      resection was performed. Histologically a gangliocytic paraganglioma was
      diagnosed, a very rare type of a duodenal neuroendocrine tumour. This case report
      discusses the epidemiology, diagnostic work-up and therapeutic options for this
      rare tumour type.

PMID- 21964897
TI  - [R classification and pancreatic ductal adenocarcinoma--R 0 is R 0].
AB  - The ductal adenocarcinoma of the pancreas is characterised by a very poor
      prognosis due to an early inoperability of the tumours. Even if operated under
      curative aspects, local recurrence of the disease is quite frequent with
      corresponding poorer prognosis. For a better assessment, standardised protocols
      for the pathohistological processing of resection specimens of the pancreas are
      needed urgently as well as a strict adherence to the R classification. In order
      to establish a reliable marker for the risk of recurrence, the smallest distance
      to the circumferential resection margin should be indicated in comparison to the
      circumferential resection margin (CRM) concept in colorectal carcinoma.

PMID- 21964896
TI  - Solid pseudopapillary tumors of the pancreas: a case series, comparison of
      histopathological and clinical data.
AB  - Solid pseudopapillary neoplasms (SPNs) are rare pancreatic tumors. They occur
      most frequently in young females and are often diagnosed accidentally. SPNs are
      characterized by an excellent clinical outcome. In our case series the clinical
      course, pathohistological data and clinical outcome of eight patients (7 female
      patients, 1 male patient) with SPN are described. Histological examination as
      well as immunohistochemical analysis shows similar results in all eight cases.
      Although in the literature a few cases of SPNs with bad prognosis have been
      reported, up to now none of our patients shows any signs of recurrence or
      metastasis. Moreover, we give in this case series a summary of SPNs in the
      literature, important clinical and pathological differential diagnosis, and
      additionally discuss relevant differential diagnosis occurring in daily routine
      work.

PMID- 21964898
TI  - [Early detection of colonic cancer in the National Cancer Program--present status
      and recommendations].
AB  - The National Cancer Programme of the German Federal Administration aims to assess
      the present status of the national fight against cancer in Germany. Experts in
      their field have analysed the present target-performance comparison in different
      working groups dealing with topics from cancer prevention to follow-up and have
      developed recommendations as to how improvements in the various fields of cancer
      care may be achieved and mainly how these imrpovements may be implemented in day
      to-day cancer care. The working group "Advancement of Colon Cancer Screening,
      Early Detection and Prevention" proposes the establishment of regulatory
      proposals for a nationwide, population-based, postal invitational process and,
      according to Pilot-Projects in Bavaria and Baden-Wuerttemberg, to evaluate the
      essential recommendations in data protection, logistics, documentation and
      financing. There are already several programmes in preparation--for example, the
      Saarland Offensive, based on the results of the KolosSal-Study.

PMID- 21964899
TI  - [Early Barrett's neoplasia--don't burn without histology].

PMID- 21964900
TI  - Hepatic mRNA, microRNA, and miR-34a-target responses in mice after 28 days
      exposure to doses of benzo(a)pyrene that elicit DNA damage and mutation.
AB  - Benzo(a)pyrene (BaP) is a mutagenic carcinogen that is ubiquitous in our
      environment. To better understand the toxic effects of BaP and to explore the
      relationship between toxicity and toxicogenomics profiles, we assessed global
      mRNA and microRNA (miRNA) expression in MutaTMMouse. Adult male mice were exposed
      by oral gavage to 25, 50, and 75 mg/kg/day BaP for 28 days. Liver tissue was
      collected 3 days following the last treatment. Initially, we established that
      exposure to BaP led to the formation of hepatic DNA adducts and mutations in the
      lacZ transgene of the MutaTMMouse. We then analyzed hepatic gene expression
      profiles. Microarray analysis of liver samples revealed 134 differentially
      expressed transcripts (adjusted P < 0.05; fold changes > 1.5). The mRNAs most
      affected were involved in xenobiotic metabolism, immune response, and the
      downstream targets of p53. In this study, we found a significant 2.0 and 3.6-fold
      increase following exposure to 50 and 75 mg/kg/day BaP, respectively, relative to
      controls for miR-34a. This miRNA is involved in p53 response. No other
      significant changes in miRNAs were observed. The protein levels of five
      experimentally confirmed miR-34a targets were examined, and no major down
      regulation was present. The results suggest that liver miRNAs are largely
      unresponsive to BaP doses that cause both DNA adducts and mutations. In summary,
      the validated miRNA and mRNA expression profiles following 28 day BaP exposure
      reflect a DNA damage response and effects on the cell cycle, consistent with the
      observed increases in DNA adducts and mutations.

PMID- 21964901
TI  - Challenges for epidemiologic research on the verge of a new era.
AB  - Although risk factor epidemiology has achieved much, it has its limitations
      (e.g., a failure to reveal causal mechanisms at multiple levels). To illustrate
      contemporary challenges for epidemiological research, we present a dialog with
      examples and argue for incorporating a "systems thinking through a life course"
      paradigm in epidemiological research. There is an increasing interest in moving
      part of public health from a discipline concerned primarily with risk factors at
      the individual level toward one concerned with complex causal patterns which
      often operate across different levels in time and space (e.g., from the molecular
      to the population, from the past to the future, and from the distal to the
      proximal). However, the methodology for discovering these complex and dynamic
      relationships remains to be improved. We propose strategies for taking up this
      challenge.

PMID- 21964902
TI  - Paris Prospective Study III: a study of novel heart rate parameters, baroreflex
      sensitivity and risk of sudden death.
AB  - Resting heart rate has been related to the risk of cardiovascular disease and
      sudden death in several large prospective studies. To investigate prospectively
      the association of novel heart rate parameters and of carotid artery stiffness
      with sudden death and other cardiovascular disease. The Paris Prospective Study
      III (PPS3) is a new, ongoing French prospective study. From June 2008 to December
      2011, 10,000 men and women aged 50-75 years who will have a preventive medical
      check-up at the Centre d'Investigations Preventives et Cliniques in Paris
      (France), will be enrolled in the study, after signing an informed consent. In
      addition to the general health examination, each subject's heart rhythm will be
      recorded during the course of the health check-up (approximately 2(1/2) h) and an
      echo-tracking of the right carotid bulb will be performed by trained technicians.
      A bio bank and DNA bank will be established for further biomarker and genetic
      analyses. The occurrence of cardiovascular disease including acute coronary
      syndrome, stroke, peripheral artery disease and sudden death, and of mortality,
      of the participants will be followed up during 20 years. With an estimated mean
      annual rate of sudden death of 0.1% and its increasing incidence rate with age,
      between 250 and 300 sudden deaths are expected. This unique study should provide
      new insights into the regulation of heart rate and blood pressure and should
      enable to identify novel heart rate parameters that are associated with sudden
      death.

PMID- 21964903
TI  - A neutron spectrometer using nested moderators.
AB  - The design, simulation results and measurements of a new neutron energy
      spectrometer are presented. The device, which may be called NNS, for Nested
      Neutron Spectrometer, works under the same principles as a Bonner Sphere
      Spectrometer (BSS) System, i.e. whereby a thermal neutron detector is surrounded
      by a polyethylene moderator. However, the moderator is cylindrical in shape. The
      different thicknesses of moderator are created by inserting one cylinder into
      another, much like nested Russian dolls. This design results in a much lighter
      instrument that is also easier to use in the field. Simulations and measurements
      show that, despite its shape, the device can be made to offer a near angular
      isotropic response to neutrons and that unfolded neutron spectra are in agreement
      with those obtained with a more traditional BSS.

PMID- 21964904
TI  - Retrospective dosimetry with alumina substrate from electronic components.
AB  - Alumina substrate can be found in electronic components used in portable
      electronic devices. The material is radiation sensitive and can be applied in
      dosimetry using thermally or optically stimulated luminescence. Electronic
      portable devices such as mobile phones, USB flash discs, mp3 players, etc., which
      are worn close to the body, can represent  personal dosemeters for members of the
      general public in situations of large-scale radiation accidents or malevolent
      acts with radioactive materials. This study investigated dosimetric properties of
      alumina substrates and aspects of using mobile phones as personal dosemeters. The
      alumina substrates exhibited favourable dosimetry characteristics. However,
      anomalous fading had to be properly corrected in order to achieve sufficient
      precision in dose estimate. Trial dose reconstruction performed by means of two
      mobile phones proved that mobile phones can be used for reconstruction of
      personal doses.

PMID- 21964905
TI  - A new methodology for studying nanoparticle interactions in biological systems:
      dispersing titania in biocompatible media using chemical stabilisers.
AB  - We report here a highly successful and original protocol for the dispersion of
      nanoparticles in biocompatible fluids for in vitro and in vivo studies of the
      nanoparticle-biology interaction. Titania is chosen as a suitable model as it is
      one of the priority materials listed by the OECD and small particles of the
      anatase structure are extensively used as e.g. photocatalysts in solar cells.
      Consequently, its delivery into the environment and its interaction with
      biological organisms is unavoidable. Therefore, its biological effect needs to be
      understood. In this work, we prepared stable nanoparticle dispersions of anatase
      aggregates using citrate stabilisations between 45 and 55 nm at concentrations of
      up to 10 mg mL(-1). The optimum pH for this type of suspension was 7, resulting
      in zeta-potentials of approximately -50 mV. The stabilised aggregates were the
      subject of dialysis to produce stable dispersions without the chemical
      stabiliser, thus allowing studies in the absence of potentially toxic chemicals.
      Different sizing techniques such as Dynamic Light Scattering (DLS), Nanoparticle
      Tracking Analysis (NTA) and Differential Centrifuge Sedimentation (DCS) were used
      to characterise the different suspensions. The results obtained with each of
      these techniques are compared and a critical analysis of the suitability of each
      technique is given.

PMID- 21964906
TI  - Pharmacokinetics of TH-302: a hypoxically activated prodrug of bromo
      isophosphoramide mustard in mice, rats, dogs and monkeys.
AB  - PURPOSE: To characterize the pharmacokinetics of the prodrug, TH-302, and its
      active metabolite, bromo-IPM (Br-IPM), in nonclinical species. METHODS: TH-302
      was administered in single oral, intraperitoneal and intravenous bolus doses to
      mice, rats, dogs and monkeys as well as in acute and chronic safety studies in
      rats and dogs as a 30-min intravenous infusion given once a week for 3 weeks.
      Assessments were made using liquid chromatography-tandem mass spectrometry.
      RESULTS: TH-302 was extensively distributed with high systemic clearance
      exceeding hepatic plasma flow in all species studied, resulting in half-lives
      ranging between 8 min (mice) and over 4 h (rats). In rats, TH-302 exhibited
      linear kinetics following intravenous administration and good oral
      bioavailability. In acute and chronic safety studies, there was no accumulation
      of TH-302 following once weekly dosing for 3 weeks in the rat and dog. Br-IPM
      plasma concentrations were a small fraction of the TH-302 plasma concentrations
      with significantly smaller percentages present in dogs than in rats. Allometric
      scaling predicted that the systemic clearance and steady-state volume of
      distribution in humans would be 38.8 l/h/m(2) and 34.3 l/m(2), respectively,
      resulting in a terminal elimination half-life of about 36 min. These values were
      similar to those observed in patients with solid tumors (27.1 l/h/m(2), 23.5
      l/m(2) and 47 min). CONCLUSIONS: TH-302 exhibited good safety, efficacy and
      pharmacokinetic properties in nonclinical species, translating into favorable
      properties in humans.

PMID- 21964907
TI  - Maximal oxygen consumption is best predicted by measures of cardiac size rather
      than function in healthy adults.
AB  - Training induces changes in cardiac structure and function which improves cardiac
      output (CO) and oxygen delivery during exercise. It is unclear whether it is
      cardiac structure or function which is of greatest importance in determining
      maximal oxygen consumption (VO(2max)). In 55 subjects (15 non-athletes, 32
      amateur and 8 elite athletes), left and right ventricular (LV and RV) volumes and
      mass were assessed by magnetic resonance imaging (CMR). Comprehensive traditional
      and novel echocardiographic measures included colour-coded Doppler
      echocardiography to assess myocardial velocities, strain and strain rate at rest
      and maximal exercise in both ventricles. Measures of cardiac size and function
      were assessed as univariate and multivariate predictors of VO(2max). LV and RV
      mass correlated strongly with VO(2max) (r = 0.79 and r = 0.65, respectively, p <
      0.0001), as did LV and RV end-diastolic volumes (r = 0.68 and r = 0.75, p <
      0.0001) and heart rate reserve (r = 0.60, p < 0.0001). Measures of myocardial
      function were not predictive of VO(2max) with the exception of RV diastolic
      velocities (r = 0.32 and r = 0.36 for rest and exercise, respectively, p < 0.05).
      On multivariate analysis, only RV end-diastolic volume, LV mass and heart rate
      reserve were independent predictors (beta = 0.28, 0.45 and 0.27 respectively, p <
      0.0001) and together explained 73% of the variance in VO(2max). Measures of
      cardiac morphology are strongly associated with VO(2max) in healthy adults and
      well-trained athletes. A combination of ventricular volume, mass and heart rate
      reserve explains much of the variance in VO(2max), whilst measures of myocardial
      function do not further strengthen predictive models.

PMID- 21964908
TI  - Inspiratory muscle training abolishes the blood lactate increase associated with
      volitional hyperpnoea superimposed on exercise and accelerates lactate and oxygen
      uptake kinetics at the onset of exercise.
AB  - We examined the effects of inspiratory muscle training (IMT) upon volitional
      hyperpnoea-mediated increases in blood lactate ([lac(-)](B)) during cycling at
      maximal lactate steady state (MLSS) power, and blood lactate and oxygen uptake
      kinetics at the onset of exercise. Twenty males formed either an IMT (n = 10) or
      control group (n = 10). Prior to and following a 6-week intervention, two 30 min
      trials were performed at MLSS (207 +/- 28 W), determined using repeated 30 min
      constant power trials. The first was a reference trial, whereas during the second
      trial, from 20 to 28 min, participants mimicked the breathing pattern
      commensurate with 90% of the maximal incremental exercise test minute ventilation
      ([Formula: see text]). Prior to the intervention, the MLSS [lac(-)](B) was 3.7 +/
      1.8 and 3.9 +/- 1.6 mmol L(-1) in the IMT and control groups, respectively.
      During volitional hyperpnoea, [Formula: see text] increased from 79.9 +/- 9.5 and
      76.3 +/- 15.4 L min(-1) at 20 min to 137.8 +/- 15.2 and 135.0 +/- 19.7 L min(-1)
      in IMT and control groups, respectively; [lac(-)](B) concurrently increased by
      1.0 +/- 0.6 (+27%) and 0.9 +/- 0.7 mmol L(-1) (+25%), respectively (P < 0.05).
      Following the intervention, maximal inspiratory mouth pressure increased 19% in
      the IMT group only (P < 0.01). Following IMT only, the increase in [lac(-)](B)
      during volitional hyperpnoea was abolished (P < 0.05). In addition, the blood
      lactate (-28%) and phase II oxygen uptake (-31%) kinetics time constants at the
      onset of exercise and the MLSS [lac(-)](B) (-15%) were reduced (P < 0.05). We
      attribute these changes to an IMT-mediated increase in the oxidative and/or
      lactate transport capacity of the inspiratory muscles.

PMID- 21964909
TI  - Effects of different levels of compression during sub-maximal and high-intensity
      exercise on erythrocyte deformability.
AB  - The aim of the study was to test the hypothesis whether different levels of sock
      compression (0, 10, 20, and 40 mmHg) affect erythrocyte deformability and
      metabolic parameters during sub-maximal and maximal running. Nine well-trained,
      male endurance athletes (age 22.2 +/- 1.3 years, peak oxygen uptake 57.7 +/- 4.5
      mL min(-1) kg(-1)) carried out four periods of sub-maximal running at 70% of peak
      oxygen uptake for 30 min followed by a ramp test until exhaustion with and
      without compression socks that applied different levels of pressure. Erythrocyte
      deformability, blood lactate, heart rate and arterial partial pressure of oxygen
      (pO(2)) were monitored before and during all of these tests. Erythrocyte
      deformability, heart rate, pO(2) and lactate concentration were unaffected by
      compression, whereas exercise itself significantly increased erythrocyte
      deformability. However, the increasing effects of exercise were attenuated when
      high compression was applied. This first evaluation of the potential effects of
      increasing levels of compression on erythrocyte deformability and metabolic
      parameters during (sub-) maximal exercise, revealed no effects whatsoever.

PMID- 21964910
TI  - Effects of successive air and nitrox dives on human vascular function.
AB  - SCUBA diving is regularly associated with asymptomatic changes in cardiac,
      pulmonary and vascular function. The aim of this study was to evaluate the
      changes in vascular/endothelial function following SCUBA diving and to assess the
      potential difference between two breathing gases: air and nitrox 36 (36% oxygen
      and 64% nitrogen). Ten divers performed two 3-day diving series (no-decompression
      dive to 18 m with 47 min bottom time with air and nitrox, respectively), with 2
      weeks pause in between. Arterial/endothelial function was assessed using
      SphygmoCor and flow-mediated dilation measurements, and concentration of nitrite
      before and after diving was determined in venous blood. Production of nitrogen
      bubbles post-dive was assessed by ultrasonic determination of venous gas bubble
      grade. Significantly higher bubbling was found after all air dives as compared to
      nitrox dives. Pulse wave velocity increased slightly (~6%), significantly after
      both air and nitrox diving, indicating an increase in arterial stiffness.
      However, augmentation index became significantly more negative after diving
      indicating smaller wave reflection. There was a trend for post-dive reduction of
      FMD after air dives; however, only nitrox diving significantly reduced FMD. No
      significant differences in blood nitrite before and after the dives were found.
      We found that nitrox diving affects systemic/vascular function more profoundly
      than air diving by reducing FMD response, most likely due to higher oxygen load.
      Both air and nitrox dives increased arterial stiffness, but decreased wave
      reflection suggesting a decrease in peripheral resistance due to exercise during
      diving. These effects of nitrox and air diving were not followed by changes in
      plasma nitrite.

PMID- 21964911
TI  - Relationship between effort sense and ventilatory response to intense exercise
      performed with reduced muscle glycogen.
AB  - The purpose of the present study was to examine the effects of muscle glycogen
      reduction on surface electromyogram (EMG) activity and effort sense and
      ventilatory responses to intense exercise (IE). Eight subjects performed an IE
      test in which IE [100-105% of peak O(2) uptake ([Formula: see text]), 2 min] was
      repeated three times (IE(1st), IE(2nd) and IE(3rd)) at 100-120-min intervals.
      Each interval consisted of 20-min passive recovery, 40-min submaximal exercise at
      ventilatory threshold intensity (51.5 +/- 2.7% of [Formula: see text]), and a
      further resting recovery for 40-60 min. Blood pH during IE and subsequent 20-min
      recovery was significantly higher in the IE(3rd) than in the IE(1st) (P < 0.05).
      Effort sense of legs during IE was significantly higher in the IE(3rd) than in
      the IE(1st) and IE(2nd). Integrated EMG (IEMG) measured in the vastus lateralis
      during IE was significantly lower in the IE(3rd) than in the IE(1st). In
      contrast, mean power frequency of the EMG was significantly higher in the IE(2nd)
      and the IE(3rd) than in the IE(1st). Ventilation ([Formula: see text]) in the
      IE(3rd) was significantly higher than that in the IE(1st) during IE and the first
      60 s after the end of IE. These results suggest that ventilatory response to IE
      is independent of metabolic acidosis and at least partly associated with effort
      sense elicited by recruitment of type II fibers.

PMID- 21964912
TI  - Establishing a professional profile of community health workers: results from a
      national study of roles, activities and training.
AB  - Community Health Workers (CHWs) have gained national recognition for their role
      in addressing health disparities and are increasingly integrated into the health
      care delivery system. There is a lack of consensus, however, regarding empirical
      evidence on the impact of CHW interventions on health outcomes. In this paper, we
      present results from the 2010 National Community Health Worker Advocacy Survey
      (NCHWAS) in an effort to strengthen a generalized understanding of the CHW
      profession that can be integrated into ongoing efforts to improve the health care
      delivery system. Results indicate that regardless of geographical location, work
      setting, and demographic characteristics, CHWs generally share similar
      professional characteristics, training preparation, and job activities. CHWs are
      likely to be female, representative of the community they serve, and to work in
      community health centers, clinics, community-based organizations, and health
      departments. The most common type of training is on-the-job and conference
      training. Most CHWs work with clients, groups, other CHWs and less frequently
      community leaders to address health issues, the most common of which are chronic
      disease, prevention and health care access. Descriptions of CHW activities
      documented in the survey demonstrate that CHWs apply core competencies in a
      synergistic manner in an effort to assure that their clients get the services
      they need. NCHWAS findings suggest that over the past 50 years, the CHW field has
      become standardized in response to the unmet needs of their communities. In
      research and practice, the field would benefit from being considered a health
      profession rather than an intervention.

PMID- 21964913
TI  - Stunted growth.

PMID- 21964914
TI  - MUC1 expression in pulmonary metastatic tumors: a comparison of primary lung
      cancer.
AB  - MUC1 expression has been described as a predictor for tumor progression and
      worsening of prognosis in various human neoplasms. However, little is known about
      the role of MUC1 expression in pulmonary metastatic tumors. The aim of this study
      is to examine the clinicopathological significance of MUC1 expression in
      pulmonary metastatic tumors (PMT). One hundred forty-seven patients with PMT who
      underwent (18)F-FDG PET before metastasectomy were included in this study. Tumor
      sections were stained by immunohistochemistry for MUC1, glucose transporter 1
      (Glut1), hypoxia-inducible-1alpha (HIF-1alpha) and vascular endothelial growth
      factor (VEGF). (18)F-FDG uptake and the expression of these biomarkers were
      correlated in primary lung cancer. MUC1 expression pattern was classified into
      high-grade polarized expression (HP), low-grade polarized expression (LP), or
      depolarized expression (DP) group. Of 147 patients, HP, LP and DP group were 9
      (6%), 114 (78%) and 24 (16%), respectively. The expression of Glut1, HIF
      1alphaand VEGF, and (18)F-FDG uptake were significantly higher in DP group than
      HP or LP groups. MUC1 expression with HP and DP pattern was significantly higher
      in primary lung cancer than in PMT, whereas, MUC1 expression with LP pattern
      yielded a significantly high positive rate in PMT. LP group was recognized in the
      majority of patients with pulmonary metastatic adenocarcinoma, especially colon
      cancer, whereas, HP group was significantly low in pulmonary metastatic
      adenocarcinoma as compared with primary adenocarcinoma. Polarized MUC1 has a
      different expression pattern between primary and metastatic tumors with
      adenocarcinoma, and depolarized MUC1 is closely associated with glucose
      metabolism and hypoxia.

PMID- 21964915
TI  - Determining the clinically important difference in visual analog scale scores in
      abuse liability studies evaluating novel opioid formulations.
AB  - PURPOSE: This study determined how the magnitude of change in positive subjective
      responses predicts clinical outcome in a treatment setting. Specifically, we
      attempted to define what constitutes a clinically important difference (CID) in
      subjective responses. METHODS: A 100-mm visual analog scale (VAS) measured
      subjective ratings of drug "high," calculated via an anchor-based method with
      published data from participants receiving sustained-release naltrexone (NTX) and
      heroin in a laboratory setting. The data were then compared to clinical outcomes
      in a treatment trial with sustained-release naltrexone. A distribution-based
      method subsequently analyzed data from participants who received ALO-01 (extended
      release morphine with sequestered NTX) to predict its abuse liability. RESULTS:
      Differences in ratings of drug high of approximately 10 mm on a 100-mm line were
      clinically significant. By extrapolation, CIDs were also found between crushed or
      intact ALO-01 and immediate-release morphine sulfate (IRMS). No CIDs were found
      between intact and crushed ALO-01. CONCLUSIONS: From laboratory and treatment
      trial data involving naltrexone, calculation of CIDs in subjective ratings of
      high is possible. Consequently, crushing/swallowing or injecting ALO-01 produces
      clinically significantly less drug high than oral or intravenous morphine alone,
      suggesting that ALO-01 has lower abuse liability by those routes than morphine
      formulations.

PMID- 21964916
TI  - Primary study of lymph node metastasis-related serum biomarkers in breast cancer.
AB  - The aim of this study was to detect the pretreatment serum protein profiles of
      breast cancer patients by mass spectrometry (MS) to screen candidate tumor
      biomarkers, which will supply a simple, accurate, and minimally invasive method
      to predict the axillary lymph node metastasis of breast cancer. We used magnetic
      bead-based weak cation-exchange chromatography followed by matrix-assisted laser
      desorption and ionization time-of-flight MS to detect proteins in the sera of 54
      cases of axillary node-negative breast cancer, 47 cases of axillary node-positive
      breast cancer, and 101 healthy controls. The protein profiles were analyzed to
      screen tumor biomarkers and lymph node metastasis-associated proteins to
      establish and verify a diagnostic model. Comparison of the protein profiles
      between the two cancer groups resulted in a total of 111 discriminate m/z peaks
      that were associated with breast cancer. Furthermore, 40 discriminate m/z peaks
      were detected between breast cancer patients with and without axillary node
      metastases. Four protein m/z peaks at 5,643, 4,651, 2,377, and 2,240 were used to
      construct a diagnosis model, and cross-validation indicated that breast cancer
      with and without axillary node metastasis was identified with 87.04% sensitivity
      (47/54), 87.23% specificity (41/47), and 87.13% accuracy (88/101). These proteins
      could potentially be used as predictive biomarkers to distinguish between breast
      cancer patients with or without lymph node metastasis.

PMID- 21964918
TI  - Update on sporadic inclusion body myositis.

PMID- 21964917
TI  - Reduced ventricular proliferation in the foetal cortex following maternal
      inflammation in the mouse.
AB  - It has been well established that maternal inflammation during pregnancy alters
      neurological function in the offspring, but its impact on cortical development
      and long-term consequences on the cytoarchitecture is largely unstudied. Here we
      report that lipopolysaccharide-induced systemic maternal inflammation in C57Bl/6
      mice at embryonic Day 13.5 of pregnancy, as early as 8 h after challenge, caused
      a significant reduction in cell proliferation in the ventricular zone of the
      developing cerebral cortex, as revealed by quantification of anti-phospho-Histone
      H3 immunoreactivity and bromodeoxyuridine pulse labelling. The angle of mitotic
      cleavage, determined from analysis of haematoxylin and eosin staining, cyclin E1
      gene expression and the pattern of beta-catenin immunoreactivity were also
      altered by the challenge, which suggests a change from symmetric to asymmetric
      division in the radial progenitor cells. Modifications of cortical lamination and
      gene expression patterns were detected at post-natal Day 8 suggesting prolonged
      consequences of these alterations during embryonic development. Cellular uptake
      of proteins from the cerebrospinal fluid was observed in brains from
      lipopolysaccharide-treated animals in radial progenitor cells. However, the
      foetal blood-brain barrier to plasma proteins remained intact. Together, these
      results indicate that maternal inflammation can disrupt the ventricular surface
      and lead to decreased cellular proliferation. Changes in cell density in Layers
      IV and V at post-natal Day 8 show that these initial changes have prolonged
      effects on cortical organization. The possible shift in the fate of progeny and
      the resulting alterations in the relative cell numbers in the cerebral cortex
      following a maternal inflammatory response shown here will require further
      investigation to determine the long-term consequences of inflammation on the
      development of neuronal circuitry and behaviour.

PMID- 21964920
TI  - Failure in psychotherapy: an introduction.
AB  - This article introduces an issue of the Journal of Clinical Psychology:In Session
      devoted to treatment failures in psychotherapy. In contrast to recent attention
      from the research perspective and cognitive-behavioral orientation, this issue
      focuses on clinical material from multiple theoretical perspectives. This article
      provides an overview of some of the empirical and definitional issues on
      treatment failure and then outlines the five subsequent articles, each of which
      offers an interesting case illustration. The article concludes with several
      transtheoretical recommendations for reducing the incidence of therapeutic
      failures.

PMID- 21964919
TI  - X-linked Angelman-like syndrome caused by Slc9a6 knockout in mice exhibits
      evidence of endosomal-lysosomal dysfunction.
AB  - Mutations in solute carrier family 9 isoform 6 on chromosome Xq26.3 encoding
      sodium-hydrogen exchanger 6, a protein mainly expressed in early and recycling
      endosomes are known to cause a complex and slowly progressive degenerative human
      neurological disease. Three resulting phenotypes have so far been reported: an X
      linked Angelman syndrome-like condition, Christianson syndrome and corticobasal
      degeneration with tau deposition, with each characterized by severe intellectual
      disability, epilepsy, autistic behaviour and ataxia. Hypothesizing that a sodium
      hydrogen exchanger 6 deficiency would most likely disrupt the endosomal-lysosomal
      system of neurons, we examined Slc9a6 knockout mice with tissue staining and
      related techniques commonly used to study lysosomal storage disorders. As a
      result, we found that sodium-hydrogen exchanger 6 depletion leads to abnormal
      accumulation of GM2 ganglioside and unesterified cholesterol within late
      endosomes and lysosomes of neurons in selective brain regions, most notably the
      basolateral nuclei of the amygdala, the CA3 and CA4 regions and dentate gyrus of
      the hippocampus and some areas of cerebral cortex. In these select neuronal
      populations, histochemical staining for beta-hexosaminidase activity, a lysosomal
      enzyme involved in the degradation of GM2 ganglioside, was undetectable.
      Neuroaxonal dystrophy similar to that observed in lysosomal disease was observed
      in the cerebellum and was accompanied by a marked and progressive loss of
      Purkinje cells, particularly in those lacking the expression of Zebrin II. On
      behavioural testing, Slc9a6 knockout mice displayed a discrete clinical phenotype
      attributable to motor hyperactivity and cerebellar dysfunction. Importantly,
      these findings show that sodium-hydrogen exchanger 6 loss of function in the
      Slc9a6-targeted mouse model leads to compromise of endosomal-lysosomal function
      similar to lysosomal disease and to conspicuous neuronal abnormalities in
      specific brain regions, which in concert could provide a unified explanation for
      the cellular and clinical phenotypes in humans with SLC9A6 mutations.

PMID- 21964921
TI  - Begomoviruses infecting weeds in Cuba: increased host range and a novel virus
      infecting Sida rhombifolia.
AB  - As a result of surveys conducted during the last few years to search for wild
      reservoirs of begomoviruses in Cuba, we detected a novel bipartite begomovirus,
      sida yellow mottle virus (SiYMoV), infecting Sida rhombifolia plants. The
      complete genome sequence was obtained, showing that DNA-A was 2622 nucleotides
      (nt) in length and that it was most closely related (87.6% nucleotide identity)
      to DNA-A of an isolate of sida golden mosaic virus (SiGMV) that infects snap
      beans (Phaseolus vulgaris) in Florida. The DNA-B sequence was 2600 nt in length
      and shared the highest nucleotide identity (75.1%) with corchorus yellow spot
      virus (CoYSV). Phylogenetic relationship analysis showed that both DNA components
      of SiYMoV were grouped in the Abutilon clade, along with begomoviruses from
      Florida and the Caribbean islands. We also present here the complete nucleotide
      sequence of a novel strain of sida yellow vein virus found infecting Malvastrum
      coromandelianum and an isolate of euphorbia mosaic virus that was found for the
      first time infecting Euphorbia heterophylla in Cuba.

PMID- 21964922
TI  - Distribution and genetic diversity of porcine hokovirus in wild boars.
AB  - Porcine hokovirus (PHoV), a newly discovered member of the family Parvoviridae
      and the proposed genus Hokovirus, is considered phylogenetically distinct from
      other parvoviruses. Here, we report a comprehensive spatio-temporal study of PHoV
      infection in Romanian wild boars. The prevalence of PHoV differed significantly
      in samples from 2006/2007 (22.76%) and 2010/2011 (50.54%), and also increased
      with age. Sequence analysis of PHoVs from 2006/2007 showed a close relationship
      to PHoVs from pigs from England and wild boars from Germany, while the PHoVs from
      2010/2011 were mostly similar to isolates from Hong Kong. The most variable
      regions were detected in the NS1 gene and proved to be suitable for analysis of
      the genetic diversity of the virus. It was observed that PHoVs from older wild
      boar samples differed from those collected recently. These results suggested that
      porcine hokovirus could be a newly emerging virus of both domestic and wild pigs
      with yet unknown implications.

PMID- 21964923
TI  - Monosodium urate (gout) crystals, an uncommon finding in ThinPrep synovial fluid
      cytology.

PMID- 21964925
TI  - Regulation of Toll-like receptor signaling by NDP52-mediated selective autophagy
      is normally inactivated by A20.
AB  - Toll-like receptor (TLR) signaling is linked to autophagy that facilitates
      elimination of intracellular pathogens. However, it is largely unknown whether
      autophagy controls TLR signaling. Here, we report that poly(I:C) stimulation
      induces selective autophagic degradation of the TLR adaptor molecule TRIF and the
      signaling molecule TRAF6, which is revealed by gene silencing of the ubiquitin
      editing enzyme A20. This type of autophagy induced formation of autophagosomes
      and could be suppressed by an autophagy inhibitor and lysosomal inhibitors.
      However, this autophagy was not associated with canonical autophagic processes,
      including involvement of Beclin-1 and conversion of LC3-I to LC3-II. Through
      screening of TRIF-interacting 'autophagy receptors' in human cells, we identified
      that NDP52 mediated the selective autophagic degradation of TRIF and TRAF6 but
      not TRAF3. NDP52 was polyubiquitinated by TRAF6 and was involved in aggregation
      of TRAF6, which may result in the selective degradation. Intriguingly, only under
      the condition of A20 silencing, NDP52 could effectively suppress poly(I:C)
      induced proinflammatory gene expression. Thus, this study clarifies a selective
      autophagic mechanism mediated by NDP52 that works downstream of TRIF-TRAF6.
      Furthermore, although A20 is known as a signaling fine-tuner to prevent excess
      TLR signaling, it paradoxically downregulates the fine-tuning effect of NDP52 on
      TLR signaling.

PMID- 21964924
TI  - Antithetic roles of proteoglycans in cancer.
AB  - Proteoglycans (PGs), a family of complex post-translationally sculptured
      macromolecules, are fundamental regulators of most normal and aberrant cellular
      functions. The unparalleled structural-functional diversity of PGs endows them
      with the ability to serve as critical mediators of the tumor cells' interaction
      with the host microenvironment, while directly contributing to the organization
      and dynamic remodeling of this milieu. Despite their indisputable importance
      during embryonic development and in the adult organism, and their frequent
      dysregulation in tumor lesions, their precise involvement in tumorigenesis awaits
      a more decisive demonstration. Particularly challenging is to ascertain to what
      extent selected PGs may catalyze tumor progression and to what extent they may
      inhibit it, implying antithetic functions of individual PGs. Integrated efforts
      are needed to consolidate the routine use of PGs in the clinical monitoring of
      cancer patients and to broaden the exploitation of these macromolecules as
      therapeutic targets. Several PGs have the required attributes to be contemplated
      as effective antigens for immunotherapeutic approaches, while the tangible
      results obtained in recent clinical trials targeting the NG2/CSPG4 transmembrane
      PG urge further development of PG-based cancer treatment modalities.

PMID- 21964926
TI  - Propagation of histone marks and epigenetic memory during normal and interrupted
      DNA replication.
AB  - Although all nucleated cells within a multicellular organism contain a complete
      copy of the genome, cell identity relies on the expression of a specific subset
      of genes. Therefore, when cells divide they must not only copy their genome to
      their daughters, but also ensure that the pattern of gene expression present
      before division is restored. While the carrier of this epigenetic memory has been
      a topic of much research and debate, post-translational modifications of histone
      proteins have emerged in the vanguard of candidates. In this paper we examine the
      mechanisms by which histone post-translational modifications are propagated
      through DNA replication and cell division, and we critically examine the evidence
      that they can also act as vectors of epigenetic memory. Finally, we consider ways
      in which epigenetic memory might be disrupted by interfering with the mechanisms
      of DNA replication.

PMID- 21964927
TI  - Epithelial homeostasis and the underlying molecular mechanisms in the gut of the
      insect model Drosophila melanogaster.
AB  - Insects mostly develop on decaying and contaminated organic matter and often
      serve as vectors of biologically transmitted diseases by transporting
      microorganisms to the plant and animal hosts. As such, insects are constantly
      ingesting microorganisms, a small fraction of which reach their epithelial
      surfaces, mainly their digestive tract, where they can establish relationships
      ranging from symbiosis to mutualism or even parasitism. Understanding the tight
      physical, genetic, and biochemical interactions that takes place between
      intestinal epithelia and either resident or infectious microbes has been a long
      lasting objective of the immunologist. Research in this field has recently been
      re-vitalized with the development of deep sequencing techniques, which allow
      qualitative and quantitative characterization of gut microbiota. Interestingly,
      the recent identification of regenerative stem cells in the Drosophila gut
      together with the initial characterization of Drosophila gut microbiota have
      opened up new avenues of study aimed at understanding the mechanisms that
      regulate the dialog between the Drosophila gut epithelium and its microbiota of
      this insect model. The fact that some of the responses are conserved across
      species combined with the power of Drosophila genetics could make this organism
      model a useful tool to further elucidate some aspects of the interaction
      occurring between the microbiota and the human gut.

PMID- 21964930
TI  - Osteocalcin gene expression is regulated by wild-type p53.
AB  - The tumor-suppressor p53 is a transcription factor that regulates a number of
      genes in the process of cell-cycle inhibition, apoptosis, and DNA damage. Recent
      studies have revealed a crucial role for p53 in bone remodeling. In our previous
      studies we have shown that p53 is an important regulator of osteoblast
      differentiation. In this study we investigated the role of p53 in the regulation
      of human osteocalcin gene expression. We observed that osteocalcin promoter
      activity could be upregulated by both exogenous and endogenous p53 and
      downregulated by p53-specific small interfering RNA. DNA affinity immunoblotting
      assay showed that p53 can bind to the human osteocalcin promoter in vitro. We
      further identified a p53 response element within the osteocalcin promoter region
      using a chromatin immunoprecipitation assay. Furthermore, we observed an additive
      effect of p53 and VDR on the regulation of osteocalcin promoter activity. Our
      findings suggest that p53 may directly target the human osteocalcin gene and
      positively affect osteocalcin gene expression.

PMID- 21964929
TI  - The small specific effects of antidepressants in clinical trials: what do they
      mean to psychiatrists?
AB  - Although antidepressants continue to be a mainstay for clinicians who treat
      people suffering from depressive disorders, there have recently been articles
      published in both the scientific literature and the popular press that have
      raised questions about the utility of this class of medications. This paper
      briefly examines recent meta-analyses that have reported small drug versus
      placebo differences in randomized controlled trials and, from the perspective of
      a prescribing psychiatrist, discusses the clinical significance of these
      findings. It is concluded that antidepressants do have relatively modest effects
      (as compared with placebo) in contemporary randomized controlled trials, and that
      the contribution of placebo-expectancy factors to individual outcomes is often
      underestimated. Nevertheless, it is also concluded that the modest benefits of
      antidepressants in grouped datasets obscure large, specific, and very meaningful
      therapeutic effects for 10% to 20% of those treated with antidepressants.

PMID- 21964931
TI  - Ginsenoside-Rg1 mediates a hypoxia-independent upregulation of hypoxia-inducible
      factor-1alpha to promote angiogenesis.
AB  - Hypoxia-inducible factor (HIF-1) is the key transcription regulator for multiple
      angiogenic factors and is an appealing target. Ginsenoside-Rg1, a nontoxic
      saponin isolated from the rhizome of Panax ginseng, exhibits potent proangiogenic
      activity and has the potential to be developed as a new angiotherapeutic agent.
      However, the mechanisms by which Rg1 promotes angiogenesis are not fully
      understood. Here, we show that Rg1 is an effective stimulator of HIF-1alpha under
      normal cellular oxygen conditions in human umbilical vein endothelial cells. HIF
      1alpha steady-state mRNA was not affected by Rg1. Rather, HIF-1alpha protein
      synthesis was stimulated by Rg1. This effect was associated with constitutive
      activation of phosphatidylinositol 3-kinase (PI3K)/Akt and its effector p70 S6
      kinase (p70(S6K)), but not extracellular-signal regulated kinase 1/2. We further
      revealed that HIF-1alpha induction triggered the expression of target genes,
      including vascular endothelial growth factor (VEGF). The use of small molecule
      inhibitors LY294002 or rapamycin to inhibit PI3K/Akt and p70(S6K) activities,
      respectively, resulted in diminished HIF-1alpha activation and subsequent VEGF
      expression. RNA interference-mediated knockdown of HIF-1alpha suppressed Rg1
      induced VEGF synthesis and angiogenic tube formation, confirming that the effect
      was HIF-1alpha specific. Similarly, the angiogenic phenotype could be reversed by
      inhibition of PI3K/Akt and p70(S6K). These results define a hypoxia-independent
      activation of HIF-1alpha, uncovering a novel mechanism for Rg1 that could play a
      major role in angiogenesis and vascular remodeling.

PMID- 21964932
TI  - Influence of temperature changes on ambient air NOx chemiluminescence
      measurements.
AB  - Users of automatic air pollution monitors are largely unaware of how certain
      parameters, like temperature, can affect readings. The present work examines the
      influence of temperature changes on chemiluminescence NO(x) measurements made
      with a Thermo Scientific 42i analyzer, a model widely used in air monitoring
      networks and air pollution studies. These changes are grouped into two categories
      according to European Standard EN 14211: (1) changes in the air surrounding the
      analyzers and (2) changes in the sampled air. First, the sensitivity tests
      described in Standard EN 14211 were performed to determine whether the analyzer
      performance was adapted to the requirements of the standard. The analyzer met the
      performance criteria of both tests; however, some differences were detected in
      readings with temperature changes even though the temperature compensator was on.
      Sample temperature changes were studied more deeply as they were the most
      critical (they cannot be controlled and differences of several tens of degrees
      can be present in a single day). Significant differences in readings were
      obtained when changing sample temperature; however, maximum deviations were
      around 3% for temperature ranges of 15 degrees C. If other possible uncertainty
      contributions are controlled and temperature variations with respect to the
      calibration temperature are not higher than 15 degrees C, the effect of
      temperature changes could be acceptable and no data correction should have to be
      applied.

PMID- 21964928
TI  - Trafficking and stability of voltage-gated calcium channels.
AB  - Voltage-gated calcium channels are important mediators of calcium influx into
      electrically excitable cells. The amount of calcium entering through this family
      of channel proteins is not only determined by the functional properties of
      channels embedded in the plasma membrane but also by the numbers of channels that
      are expressed at the cell surface. The trafficking of channels is controlled by
      numerous processes, including co-assembly with ancillary calcium channel
      subunits, ubiquitin ligases, and interactions with other membrane proteins such
      as G protein coupled receptors. Here we provide an overview about the current
      state of knowledge of calcium channel trafficking to the cell membrane, and of
      the mechanisms regulating the stability and internalization of this important ion
      channel family.

PMID- 21964933
TI  - [Frequency of using the bedpan in acute care].
AB  - Although the bedpan is a subject of everyday nursing practice, little research
      was found concerning this issue. Patients often describe that the use of the
      bedpan is uncomfortable and painful. Studies also underline that using a bedpan
      is very embarrassing and shameful for the patients. Their privacy is violated
      considerably. In this quantitative descriptive cross-sectional study, the
      frequency and duration of use of the bedpan was measured in acute care. 362 women
      and 367 men were included in the study, 18.2 % of them needed the bedpan for a
      certain time. It was used more often during the night than during the day,
      departmental differences were also identified. Women used the bedpan most at the
      orthopedic and medical wards, followed by the prenatal ward (for urine). Men from
      surgical wards used the bedpan most (12.3 %), followed by medical wards (8.3 %).
      Most patients required assistance while using the bedpan. Because of this the
      resulting workload for nurses should be underestimated. The introduction of
      alternative urine drainage systems could lead to more autonomy of patients and
      might reduce the workload for nurses.

PMID- 21964934
TI  - [The influence of understanding diagnostics on perceived stress of nurses caring
      for nursing home residents with dementia].
AB  - Health services for nursing home residents with dementia require the expertise of
      highly trained nursing staff. In addition, dealing with challenging behaviour of
      people with dementia is often stressful for nurses and causes major difficulties
      for them. Being a part of the general nursing guidelines, "understanding
      diagnostics" enables nursing staff to deal with challenging behaviour of persons
      with dementia. The primary focus of the concept is to understand the behaviour.
      The aim of the study was to implement and evaluate "understanding diagnostics"
      through structured case conferences and the application of the 'Innovative
      dementia-oriented Assessment system' (IdA) in nursing homes for the first time.
      Nursing staff of 15 nursing homes in North- Rhine Westphalia were trained about
      the content and implementation of "understanding diagnostics". Nurses' perceived
      level of stress was measured before (n = 106) and after (n = 71) the intervention
      (9 months). The study results show positive effects on the nurses' perceived
      level of stress. They support the use of structured case conferences and the IdA
      assessment in order to understand the behaviour of nursing residents with
      dementia. The implementation of "understanding diagnostics" allows nursing staff
      to deal with challenging behaviour of nursing home residents with dementia.

PMID- 21964935
TI  - [In-patient education after renal transplantation].
AB  - Patients with end-stage renal disease who receive a kidney through
      transplantation enter a new phase in their illness trajectory. The question
      emerged which knowledge and skills are essential for a safe self-management
      immediately after the transplantation. The aim of this project was to develop an
      evidence-based in-patient education programme for renal transplant recipients. A
      participative action research approach was chosen. An interprofessional group,
      led by an advanced practice nurse, initiated the project. Based on a systematic
      literature review and on qualitative interviews with both patients and experts,
      an in-patient educational programme was developed and implemented. The main
      elements of the programme focused on taking medications appropriately and on the
      observation and interpretation of symptoms. The content of the programme was
      documented in a brochure for patients. The structure of the programme was
      documented in a guideline with a standardised procedure. The procedure was based
      on patients' needs and preferences, and therefore provides tailored education.
      Besides the support received in gaining relevant knowledge, patients are
      supported in developing practical skills, problem solving, and decision making.
      An initial evaluation revealed that patients with cognitive impairment have
      special needs for education that exceeds what exists in the developed programme.
      As the programme is revised, additional contents on psychosocial issues will be
      included and the programme will be planned along the clinical pathway.
      Furthermore, it should begin during the pre-transplant period and continue in a
      longterm follow-up.

PMID- 21964936
TI  - Wavelength tunable electroluminescence from randomly assembled n-CdS(x)Se(1-x)
      nanowires/p+-SiC heterojunction.
AB  - Visible electroluminescence (EL) with tunable wavelength has been observed at
      room temperature from randomly assembled n-CdS(x)Se(1-x) nanowires grown on a
      p(+)-SiC substrate by the vapor transport technique. The dominant emission peaks
      can be tuned from ~720 to ~520 nm by varying the composition of the alloy
      nanowires.

PMID- 21964937
TI  - HIV testing behaviors among undocumented Central American immigrant women in
      Houston, Texas.
AB  - This paper describes HIV testing behaviors among undocumented Central American
      immigrant women living in Houston, Texas, USA. Respondent driven sampling was
      used to recruit participants for an HIV behavioral survey. HIV testing items
      included lifetime history of testing, date and location of the most recent test,
      and reason for testing. Multivariate logistic regression was used to assess the
      demographic, behavioral, and structural characteristics associated with testing.
      The lifetime prevalence of HIV testing was 67%. Half of those who tested did so
      within the past 2 years and almost 80% received their most recent test in a
      healthcare setting. The primary reason for testing was pregnancy. Lifetime
      testing was associated with being from Honduras, having over a sixth grade
      education, having a regular healthcare provider, and having knowledge of
      available healthcare resources. Our results suggest that expanding access to
      healthcare services may increase the prevalence of HIV testing in this
      population.

PMID- 21964938
TI  - Ganglion cell distribution and retinal resolution in the Florida manatee,
      Trichechus manatus latirostris.
AB  - The topographic organization of retinal ganglion cells was examined in the
      Florida manatee (Trichechus manatus latirostris) to assess ganglion cell size and
      distribution and to estimate retinal resolution. The ganglion cell layer of the
      manatee's retina was comprised primarily of large neurons with broad
      intercellular spaces. Cell sizes varied from 10 to 60 MUm in diameter (mean 24.3
      MUm). The retinal wholemounts from adult animals measured 446-501 mm(2) in area
      with total ganglion cell counts of 62,000-81,800 (mean 70,200). The cell density
      changed across the retina, with the maximum in the area below the optic disc and
      decreasing toward the retinal edges and in the immediate vicinity of the optic
      disc. The maximum cell density ranged from 235 to 337 cells per millimeter square
      in the adult retinae. Two wholemounts obtained from juvenile animals were 271 and
      282 mm(2) in area with total cell numbers of 70,900 and 68,700, respectively
      (mean 69,800), that is, nearly equivalent to those of adults, but juvenile
      retinae consequently had maximum cell densities that were higher than those of
      adults: 478 and 491 cells per millimeter square. Calculations indicate a retinal
      resolution of ~19' (1.6 cycles per degree) in both adult and juvenile retinae.

PMID- 21964939
TI  - Influences of ORF1 on the virulence and immunogenicity of Actinobacillus
      pleuropneumoniae.
AB  - Actinobacillus pleuropneumoniae is a Gram-negative pathogen that causes porcine
      pleuropneumonia. The pathogenicity of A. pleuropneumoniae is strongly correlated
      with the production of active repeat-in-toxin (RTX) proteins such as ApxIVA. We
      evaluated the contribution of a potential ApxIVA activator, ORF1, to the
      virulence and immunogenicity of A. pleuropneumoniae in pigs. The orf1 gene in A.
      pleuropneumoniae SLW03 (serovar 1, DeltaapxICDeltaapxIIC) was deleted, producing
      strain SLW05 (DeltaapxICDeltaapxIICDeltaorf1). The virulence of strains SLW03 and
      SLW05 was compared in pigs. Clinical signs and pulmonary lesions induced by
      strain SLW05 were slighter than that of strain SLW03 (P < 0.05). The
      immunogenicity and protective efficacy of strains SLW03 and SLW05 were similar.
      All pigs immunized with strain SLW03 or SLW05 developed high antibody titers
      against ApxIA, ApxIIA, and ApxIVA before challenge. Two weeks after a second
      immunization, pigs were challenged intratracheally with either a fully virulent
      A. pleuropneumoniae serovar 1 or serovar 3 strain. Vaccination with strains SLW03
      or SLW05 provided significantly greater protection compared to the negative
      control (P < 0.01). Immunized pigs displayed significantly fewer clinical signs
      and lower lung lesion scores than non-immunized pigs. These results suggested
      that ORF1 plays an important role in the development of ApxIVA toxicity.
      Furthermore, strain SLW05 is a highly attenuated strain able to induce protective
      immunity against A. pleuropneumoniae infection.

PMID- 21964940
TI  - Holocellulase activity from Schizophyllum commune grown on bamboo: a comparison
      with different substrates.
AB  - The natural biodiversity that is found in tropical areas offers countless
      biotechnological opportunities; especially if we take in account that many
      biomolecules from several microorganisms have supported for many years, different
      industrial applications in areas such as pharmacology, agro-industry, bioprocess,
      environmental technology, and bioconversion. In order to find new
      lignocellulolytic enzymes and evaluate bamboo fibers as substrate, Schizophyllum
      commune a fungus with broad distribution was isolated and grown during 15 days in
      liquid culture medium containing 1% lignocellulosic fibers from bamboo, banana
      stem, and sugarcane bagasse. The enzymatic activity of xylanase, mannanase,
      polygalacturonase, CMCase, FPase, and avicelase were evaluated. Sugarcane bagasse
      and banana stem showed to induce higher hollocellulase activity when compared
      with bamboo as the main carbon source. The physical mechanism that the fungus
      uses to degrade bamboo was observed not only in fibers naturally infected but
      also in healthy fibers that were treated and untreated with enzyme solution. SEM
      analysis showed the structural disruption and invasion of the vascular bundles,
      parenchyma cells, and parenchymatous tissues as a consequence of the presence of
      this fungus and the catalytic action of its enzymes into the plant tissue.

PMID- 21964941
TI  - Ataxia rating scales--psychometric profiles, natural history and their
      application in clinical trials.
AB  - We aimed to perform a comprehensive systematic review of the existing ataxia
      scales. We described the disorders for which the instruments have been validated
      and used, the time spent in its application, its validated psychometric
      properties, and their use in studies of natural history and clinical trials. A
      search from 1997 onwards was performed in the MEDLINE, LILACS, and Cochrane
      databases. The web sites ClinicalTrials.gov and Orpha.net were also used to
      identify the endpoints used in ongoing randomized clinical trials. We identified
      and described the semiquantitative ataxia scales (ICARS, SARA, MICARS, BARS);
      semiquantitative ataxia and non-ataxia scales (UMSARS, FARS, NESSCA); a
      semiquantitative non-ataxia scale (INAS); quantitative ataxia scales (CATSYS
      2000, AFCS, CCFS and CCFSw, and SCAFI); and the self-performed ataxia scale
      (FAIS). SARA and ICARS were the best studied and validated so far, and their
      reliability sustain their use. Ataxia and non-ataxia scores will probably provide
      a better view of the overall disability in long-term trials and studies of
      natural history. Up to now, no clear advantage has been disclosed for any of
      them; however, we recommend the use of specific measurements of gait since gait
      ataxia is the first significant manifestation in the majority of ataxia disorders
      and comment on the best scales to be used in specific ataxia forms. Quantitative
      ataxia scales will be needed to speed up evidence from phase II clinical trials,
      from trials focused on the early phase of diseases, and for secondary endpoints
      in phase III trials. Finally, it is worth remembering that estimation of the
      actual minimal clinically relevant difference is still lacking; this, together
      with changes in quality of life, will probably be the main endpoints to measure
      in future therapeutic studies.

PMID- 21964942
TI  - Body regional influences of L-menthol application on the alleviation of heat
      strain while wearing firefighter's protective clothing.
AB  - The purpose of this study was to investigate the influences of menthol
      application according to the amount of surface area on physiological and
      psychological heat strains, along with body regional influences. Male students
      underwent two stages of experiments: [Experiment 1] Cutaneous thermal threshold
      test at rest on eight body regions with/without a 0.8% menthol application at T
      (a) 28 degrees C and 50% RH; [Experiment 2] Six exercise tests with/without a
      0.8% menthol spray at T (a) 28 degrees C and 40% RH, while wearing firefighter's
      protective clothing (No menthol, PC(NO); Face and neck menthol, PC(FN); Upper
      body menthol, PC(UP); Whole body menthol application, PC(WB)) or wearing normal
      clothing (No menthol, NC(NO); Upper body menthol, NC(UP)). Experiment 1 showed
      that menthol caused no significant influence on cutaneous warm thresholds, while
      menthol applications evoked earlier detection of cool sensations, especially on
      the chest (P = 0.043). Experiment 2 revealed that NC(UP), PC(UP) and PC(WB)
      caused lower mean skin temperature, especially with higher peripheral
      vasoconstrictions on the extremities at rest. During exercise, NC(UP), PC(UP) and
      PC(WB) induced greater and earlier increases in rectal temperatures (T (re)) and
      a delayed sweat response, but lessened psychological burdens (P < 0.05). Both
      physiological and psychological effects of PC(FN) were insignificant. For a
      composite analysis, individual Menthol Sensitivity Index at cooling in Experiment
      1 had significant relationships with the threshold for T (re) increase and
      changes in heart rate in NC(UP) of Experiment 2 (P < 0.05). Our results indicate
      that menthol's topical influence is body region-dependent, as well as depending
      on the exposed body surface area.

PMID- 21964943
TI  - A preliminary study on the molecular evolution of the two routes of intrauterine
      transmission of HBV.
AB  - Intrauterine transmission of hepatitis B virus (HBV) is one of the main reasons
      for the failure of vaccination and plays an important role in areas with high HBV
      prevalence. In the present study, the quasispecies isolated from eight pairs of
      HBsAg-positive mothers and their neonates, who were infected with HBV by
      intrauterine transmission, were selected as study subjects. Phylogenetic trees of
      the HBV strains of each pair of mother and neonate were constructed, the
      topological structures were compared, and the distance between and within the
      quasispecies was calculated. The eight phylogenetic trees included four types. In
      the first type, the maternal and neonatal sequences clustered into one clade. In
      the second type, the sequences of the mothers and neonates formed separate
      monophyletic clusters, and the two clades were sister groups. In the third type,
      the strains of mother were the ancestors of the neonatal strains. In the fourth
      type, the strains of the mothers clustered with only some of the sequences of the
      neonate, and the other strains of the neonate formed another monophyletic group.
      Combined with the genetic distance, possible transmission routes of the eight
      cases are proposed.

PMID- 21964944
TI  - Genetic characterization and phylogenetic analysis of porcine circovirus type 2
      (PCV2) in Serbia.
AB  - Porcine circovirus type 2 (PCV2) is the main causative agent of postweaning
      multisystemic wasting syndrome (PMWS). To characterize and determine the genetic
      diversity of PCV2 in the porcine population of Serbia, nucleotide and deduced
      amino acid sequences of the open reading frame 2 (ORF2) of PCV2 collected from
      the tissues of pigs that either had died as a result of PMWS or did not exhibit
      disease symptoms were analyzed. Sequencing and phylogenetic analysis showed
      considerable diversity among PCV2 ORF2 sequences and the existence of two main
      PCV2 genotypes, PCV2b and PCV2a, with at least three clusters, 1A/B, 1C and 2D.
      In order to provide further proof that the 1C strain is circulating in the
      porcine population, the whole viral genome of one PCV2 isolate was sequenced.
      Genotyping and phylogenetic analysis using the entire viral genome sequences
      confirmed that there was a PMWS-associated 1C strain emerging in Serbia. Our
      analysis also showed that PCV2b is dominant in the porcine population, and that
      it is exclusively associated with PMWS occurrences in the country. These data
      constitute a useful basis for further epidemiological studies regarding the
      heterogeneity of PCV2 strains on the European continent.

PMID- 21964945
TI  - Variability in the P1 gene helps to refine phylogenetic relationships among leek
      yellow stripe virus isolates from garlic.
AB  - Nucleotide sequences from the P1 gene and the 5' untranslated region of leek
      yellow stripe virus (LYSV), collected from several locations, were used to refine
      the phylogenetic relationships among the isolates. Multiple alignments revealed
      three distinct regions of insertions and deletions to classify LYSVs. In our
      phylogenetic analyses, the LYSV isolates separated into two major groups (N-type
      and S-type). S-type viruses had two large deletions compared to N-type viruses.
      Considering that the outgroup, onion yellow dwarf virus (OYDV) also has the
      sequences corresponding to the deletions in the S-type viruses, our study shows
      that the sequences missing in the S-type were present in the common ancestor of
      the N-type and S-type. In the phylogenetic trees, we found three distinct clades
      of isolates, from Uruguay (U), Okinawa (O) and Spain (Sp), suggesting that LYSVs
      have unique evolutionary histories depending on their garlic origins. The P1 gene
      of LYSV is thus quite suited to reflecting viral evolution, as recently suggested
      for other potyviruses.

PMID- 21964946
TI  - Ten-year quality of life outcomes among patients with schizophrenia and
      schizoaffective disorder II. Predictive value of psychosocial factors.
AB  - PURPOSE: To identify psychosocial predictors of change in health-related quality
      of life among patients with schizophrenia (SZ) and schizoaffective (SA) disorders
      over a 10-year period. METHODS: In a naturalistic longitudinal design, 108
      patients with SZ/SA disorders completed a comprehensive rating scale battery
      including self-reported quality of life, emotional distress symptoms, coping
      styles, sense of self-efficacy, and social support, as well as observer-rated
      psychopathology, medication side effects, and general functioning at 2 time
      points, baseline and 10 years later. RESULTS: Regression models revealed that
      reduction in self-reported symptoms of depression, sensitivity or anxiety along
      with increase in self-efficacy, social support, and emotion-oriented coping
      scores predicted improvement in domain-specific perceived quality of life.
      Adjustment of the psychosocial models for the effects of disorder-related factors
      (psychopathology, functioning, and medication side effects) confirmed the above
      findings and amplified their statistical power. CONCLUSIONS: In the long-term
      course of severe mental disorders (SZ/SA), changes in the psychosocial factors
      are stronger predictors of subjective quality of life outcome than disorder
      related changes. The findings enable better understanding of the combined effects
      of psychopathology and psychosocial factors on quality of life outcome over a 10
      year period.

PMID- 21964947
TI  - The internal responsiveness of the Oral Health Impact Profile-14 to detect
      differences in clinical parameters related to surgical third molar removal.
AB  - PURPOSE: The present study examined the internal responsiveness of the short-form
      Oral Health Impact Profile (OHIP-14) and its ability to differentiate between
      patients with and without pre- and postoperative complaints as well as other
      clinical variables. METHODS: The sample consisted of 97 patients undergoing
      surgical third molar removal. The OHIP-14 was filled in preoperatively, on each
      postoperative day for a week and once more after 1 month. In addition, pre- and
      postoperative status was measured along with other clinical variables. RESULTS:
      The OHIP-14 is able to differentiate between the first preoperative day (M =
      16.85, SD = 5.35) and all the days within the postoperative week (first day M =
      29.46, SD = 9.32). One month postoperatively, mean OHIP scores are reduced to
      preoperative levels. In addition, differences could be shown between patients
      with and without pre- (M = 18.9, SD = 8.1 vs. M = 16.2, SD = 3.9) and
      postoperative complaints (M = 18.9, SD = 8.1 vs. M = 16.2, SD = 3.9), partial
      (preop; M = 17.8, SD = 6.8, postoperative; M = 27.4, SD = 7.7) and complete
      mucosa coverage (preop; M = 15.9, SD = 3.2, postoperative; M = 29.5, SD = 10.6)
      and the level of impaction (Pell and Gregory classification) of the third molar
      (3B showing the highest increase in the mean OHIP score). CONCLUSIONS: The OHIP
      14 can be considered internally responsive to changes in impacts of oral
      conditions as a result of surgical third molar removal and is able to
      differentiate the effect of several clinical variables.

PMID- 21964948
TI  - The imbalance of Th17/Th1/Tregs in patients with type 2 diabetes: relationship
      with metabolic factors and complications.
AB  - Immune disorders are linked to the development of type 2 diabetes (T2D) and its
      complications. The relationship of CD4(+)CD25(hi) T regulatory cells (Treg) and
      pro-inflammatory Th17 and Th1 subsets in T2D patients with metabolic disorders
      and complications need to be determined. The ratios of CD4(+)CD25(hi) Treg/Th17
      cells and CD4(+)CD25(hi) Treg/Th1 cells, but not Th17/Th1 cells, were
      significantly decreased in T2D patients. The thymic output
      CD4(+)Foxp3(+)Helios(+) Tregs were normal but peripheral induced
      CD4(+)Foxp3(+)Helios(-) Tregs were decreased in T2D patients. The Bcl-2/Bax ratio
      decreased in CD4(+)CD25(hi) Tregs in T2D patients, supporting the increased
      sensitivity to cell death of these cells in T2D. CD4(+)CD25(hi)CD127(-) Tregs in
      T2D patients with microvascular complications were significantly less than T2D
      patients with macrovascular complications. Importantly, CD4(+)CD25(hi)CD127(-)
      Tregs were positively correlated with plasma IL-6, whereas IL-17(+)CD4(+)cells
      were negatively related to high-density lipoprotein (HDL). Our data offered
      evidence for the skewed balance of anti- and pro-inflammatory T cell subsets in
      T2D patients and identified that HDL closely modulate T cell polarization. These
      results opened an alternative explanation for the substantial activation of
      immune cells as well as the development of T2D and complications, which may have
      significant impacts on the prevention and treatment of T2D patients.

PMID- 21964950
TI  - Vitamin D Status in Israeli subjects before the initiation and after the
      cessation of vitamin D supplements.
AB  - Vitamin D supplements are often recommended to restore sufficiency, although the
      adherence to treatment is low. This study assessed vitamin D status at different
      time intervals following the cessation of treatment. The database of Clalit
      Health-Services (CHS), a not-for-profit HMO covering more than half of the
      Israeli population, was retrospectively searched for all members with available
      serum 25OHD test results in 2009 (245,493). We then identified those who filled
      any cholecalciferol prescription in 2008-2009 (121,817). Subjects were included
      in the final analysis only if they started treatment in 2009, had serum 25OHD <
      50 nmol/l before the first prescription in 2009, and had at least one additional
      test result after the last dated prescription in 2009 (5,461). Serum 25OHD
      increased from 32 +/- 11 nmol/l at baseline to 58.6 +/- 22.3 nmol/l after
      treatment (P < 0.001). The proportion of subjects with sufficient vitamin D after
      treatment increased with increasing cholecalciferol daily dose and treatment
      duration (P < 0.001) and decreased with increasing time from cessation of
      treatment (P < 0.001). The effect of time from treatment cessation persisted
      after controlling for baseline serum 25OHD, daily cholecalciferol dose, treatment
      duration, seasonality, gender, age, ethnicity, and BMI; the ORs for sufficient
      vitamin D were 2.02 (95% CI 1.66-2.45), 1.67 (1.39-2.01), and 1.23 (1.04-1.47)
      for >30-60, 61-99, and 100-155 days compared to >155 days, respectively. Long
      term vitamin D treatment is needed to maintain sufficient levels in those with
      baseline serum 25OHD below 50 nmol/l.

PMID- 21964951
TI  - Measurement precision for repeat examinees on a standardized patient examination.
AB  - Examinees who initially fail and later repeat an SP-based clinical skills exam
      typically exhibit large score gains on their second attempt, suggesting the
      possibility that examinees were not well measured on one of those attempts. This
      study evaluates score precision for examinees who repeated an SP-based clinical
      skills test administered as part of the US Medical Licensing Examination
      sequence. Generalizability theory was used as the basis for computing conditional
      standard errors of measurement (SEM) for individual examinees. Conditional SEMs
      were computed for approximately 60,000 single-take examinees and 5,000 repeat
      examinees who completed the Step 2 Clinical Skills Examination((r)) between 2007
      and 2009. The study focused exclusively on ratings of communication and
      interpersonal skills. Conditional SEMs for single-take and repeat examinees were
      nearly indistinguishable across most of the score scale. US graduates and IMGs
      were measured with equal levels of precision at all score levels, as were
      examinees with differing levels of skill speaking English. There was no evidence
      that examinees with the largest score changes were measured poorly on either
      their first or second attempt. The large score increases for repeat examinees on
      this SP-based exam probably cannot be attributed to unexpectedly large errors of
      measurement.

PMID- 21964949
TI  - Influence of polymorphisms in the RANKL/RANK/OPG signaling pathway on volumetric
      bone mineral density and bone geometry at the forearm in men.
AB  - We sought to determine the influence of single-nucleotide polymorphisms (SNPs) in
      RANKL, RANK, and OPG on volumetric bone mineral density (vBMD) and bone geometry
      at the radius in men. Pairwise tag SNPs (r (2) >= 0.8) for RANKL (n = 8), RANK (n
      = 44), and OPG (n = 22) and five SNPs near RANKL and OPG strongly associated with
      areal BMD in genomewide association studies were previously genotyped in men aged
      40-79 years in the European Male Ageing Study (EMAS). Here, these SNPs were
      analyzed in a subsample of men (n = 589) who had peripheral quantitative computed
      tomography (pQCT) performed at the distal (4%) and mid-shaft (50%) radius.
      Estimated parameters were total and trabecular vBMD (mg/mm(3)) and cross
      sectional area (mm(2)) at the 4% site and cortical vBMD (mg/mm(3)); total,
      cortical, and medullary area (mm(2)); cortical thickness (mm); and stress strain
      index (SSI) (mm(3)) at the 50% site. We identified 12 OPG SNPs associated with
      vBMD and/or geometric parameters, including rs10505348 associated with total vBMD
      (beta [95% CI] = 9.35 [2.12-16.58], P = 0.011), cortical vBMD (beta [95% CI] =
      5.62 [2.10-9.14], P = 0.002), cortical thickness (beta [95% CI] = 0.08 [0.03
      0.13], P = 0.002), and medullary area (beta [95% CI] = -2.90 [-4.94 to -0.86], P
      = 0.005) and rs2073618 associated with cortical vBMD (beta [95% CI] = -4.30 [
      7.78 to -0.82], P = 0.015) and cortical thickness (beta [95% CI] = -0.08 [-0.13
      to -0.03], P = 0.001). Three RANK SNPs were associated with vBMD, including
      rs12956925 associated with trabecular vBMD (beta [95% CI] = -7.58 [-14.01 to 
      1.15], P = 0.021). There were five RANK SNPs associated with geometric
      parameters, including rs8083511 associated with distal radius cross-sectional
      area (beta [95% CI] = 8.90 [0.92-16.88], P = 0.029). No significant association
      was observed between RANKL SNPs and pQCT parameters. Our findings suggest that
      genetic variation in OPG and RANK influences radius vBMD and geometry in men.

PMID- 21964952
TI  - Commentary: The response process validity of a script concordance test item.

PMID- 21964953
TI  - Service learning in medical and nursing training: a randomized controlled trial.
AB  - The purpose of this study was to explore the long term effect of a service
      learning project on medical and nursing students' knowledge in aging and their
      attitudes toward older adults. A total of 124 students were recruited and then
      randomized to intervention group (IG) and control group (CG). A pre-and-post
      intervention design measured students' knowledge in aging (using modified
      Palmore's Fact on Aging Quiz) and attitudes toward older adults (using Kogan's
      Old People Scale). A total of 103 students completed all the activities and
      questionnaires. After the intervention, there were significant differences
      between the IG and CG on Palmore's mental health (MH) (P = .04), Palmore's total
      score (P = .02) and Kogan's negative attitudes toward older adults (P = .001).
      All students increased their positive attitude toward older adults after the
      intervention. However, both the IG and CG showed a decrease in positive attitudes
      1 month after the interventon, and such decrease varied, depending on the
      programme which students attended. The current study showed that the 10-week
      service learning activities significantly increased medical and nursing students'
      overall knowledge of aging and their understanding of mental health needs in old
      age, and reduced their negative attitudes toward older adults. However, the
      effect is not long-lasting. On the other hand, its effect on positive attitudes
      toward older adults cannot be concluded. Periodic contacts with older adults via
      service learning activities may be needed to sustain attitude change toward older
      adults.

PMID- 21964954
TI  - The Clinical and Pathological Features of IgG(4)-Related Disease.
AB  - The rapidly emerging disorder now known as IgG(4)-related disease (IgG(4)-RD)
      includes a variety of clinical entities once regarded as being entirely separate
      diseases. Manifestations of IgG(4)-RD have now been reported in essentially all
      organ systems. Regardless of which organ is involved, tissue biopsies reveal
      striking histopathological similarities. The hallmark pathology findings are
      diffuse lymphoplasmacytic infiltrates, abundant IgG(4)-positive plasma cells,
      modest tissue eosinophilia, and extensive fibrosis. Tumorous swelling and
      obliterative phlebitis are other frequently observed features. Polyclonal
      elevations of serum IgG(4) are found in approximately 70% of patients. Many
      questions pertaining to the etiology, pathophysiology, epidemiology, clinical
      features, therapy, disease monitoring, and long-term outcomes remain to be
      addressed. This paper focuses on the clinical and pathological features of IgG(4)
      RD.

PMID- 21964955
TI  - Statins amplify TLR-induced responses in microglia via inhibition of cholesterol
      biosynthesis.
AB  - Statins inhibit the endogenous intracellular mevalonate pathway and exposure to
      statins affects innate and adaptive immune responses. Different statins are
      currently under evaluation as (co)therapy in neuro-inflammatory diseases like
      multiple sclerosis. However, there are important discrepancies in the reported
      effects of statins on innate immune responses in different cell types. Studies to
      characterize such responses in clinically relevant primary cells are currently
      lacking. In this study, we investigated the effect of statins on Toll-like
      receptor (TLR)-induced responses of microglia, the resident macrophages of the
      central nervous system (CNS). Exposure of primary microglia from adult rhesus
      monkeys to different statins strongly amplified pro-inflammatory cytokine protein
      and mRNA levels in response to myeloid differentiation primary response gene 88
      dependent TLR activation in particular. Rather than affecting nuclear facor
      kappaB activation levels, statin exposure affected stress-activated protein/Jun
      amino-terminal and p38 kinase signaling pathways. Mechanistic studies using
      specific pathway inhibitors and rescue experiments show that statin-induced
      inhibition of cholesterol biosynthesis, rather than inhibition of isoprenylation,
      was mainly responsible for the amplified TLR responses. Additionally, microglia
      were more sensitive to statin-mediated effects than bone marrow-derived
      macrophages of the same donor. This correlated to lower intrinsic microglial
      expression levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the enzyme
      targeted by statins. Amplification of TLR-induced responses in microglia by
      statin exposure might contribute to the generation of a more pro-inflammatory CNS
      microenvironment which can be of relevance for the pathogenesis of
      neuroinflammatory disorders.

PMID- 21964956
TI  - Sirolimus-based immunosuppression in liver transplantation for hepatocellular
      carcinoma: a meta-analysis.
AB  - Sirolimus (SRL) is a novel immunosuppressant with antitumor properties. We
      performed a meta-analysis to determine whether SRL can improve patient survival
      and decrease the risks of tumor recurrence in patients with a pretransplant
      diagnosis of hepatocellular carcinoma (HCC). We searched databases for controlled
      clinical trials assessing the survival and oncological benefits of SRL for liver
      transplant recipients with pretransplant HCC. Five studies with a total of 2950
      participants were included in this study. In comparison with SRL-free regimens,
      SRL-based regimens improved overall survival at 1 [odds ratio (OR) = 4.53, 95%
      confidence interval (95% CI) = 2.31-8.89], 3 (OR = 1.97, 95% CI = 1.29-3.00), and
      5 years (OR = 2.47, 95% CI = 1.72-3.55). The pooled results showed that in
      comparison with SRL-free regimens, SRL-based regimens decreased tumor recurrence
      (OR = 0.42, 95% CI = 0.21-0.83). No significant differences in the frequencies of
      episodes of major posttransplant complications were observed between the groups.
      In conclusion, SRL is generally safe and prolongs patient survival in liver
      transplant recipients with pretransplant HCC.

PMID- 21964957
TI  - Clinical impact of second opinion in thyroid fine needle aspiration cytology
      (FNAC): A study of 922 interinstitutional consultations.
AB  - Interinstitutional consultation in pathology has shown to improve patient safety
      by detecting interpretive errors that may significantly impact clinical
      management. We conducted a study of 922 cases of thyroid FNAC slides, referred to
      our institution over a 2-year period, to assess the magnitude of discrepancies
      and determine the clinical impact of second opinion. Disagreements were
      categorized as none, minor or major, the latter two defined as one- or two-step
      deviations respectively on the NCI diagnostic categories scale. There were 122
      disagreements (13%), including 44 major and 78 minor. Seventy-five patients
      underwent a change in management based on second opinion, in conjunction with
      clinical and radiologic findings (age, size of nodule, family history,
      ultrasonographic appearance, and solitary versus multiple nodules). The second
      opinion was supported on follow-up in 57% of major discrepancies, and the initial
      diagnosis was concurrent with the surgical diagnosis in 7% cases. The remainder
      (36%) of major discrepancy cases did not undergo surgery, precluding tissue
      confirmation. Critics have alleged increased costs due to interinstitutional
      consultations. However, cost avoidance from lost wages, potential surgical
      complications, and litigation is not easily quantified. Using a simplified
      calculation to objectively measure the costs associated with changed diagnoses,
      we estimate that second opinion of these 922 cases resulted in potential cost
      saving of $940,166 based on current Medicare reimbursement codes. Our study
      indicates the need for a quality-control program of outside thyroid FNA slides,
      especially in "high discrepancy categories" as discussed in the article.

PMID- 21964958
TI  - Depressed mothers as informants on child behavior: methodological issues.
AB  - Mothers with depressive symptoms more frequently report behavioral problems among
      their children than non-depressed mothers leading to a debate regarding the
      accuracy of depressed mothers as informants of children's behavior. The purpose
      of this integrative review was to identify methodological challenges in research
      related to the debate. Data were extracted from 43 articles (6 theoretical, 36
      research reports, and 1 instrument scoring manual). The analysis focused on the
      methodologies considered when using depressed mothers as informants. Nine key
      themes were identified and I concluded that researchers should incorporate
      multiple informants, identify the characteristics of maternal depression, and
      incorporate advanced statistical methodology. The use of a conceptual framework
      to understand informant discrepancies within child behavior evaluations is
      suggested for future research.

PMID- 21964959
TI  - Testicular function and physical outcome in young adult males diagnosed with
      idiopathic 46 XY disorders of sex development during childhood.
AB  - OBJECTIVE: There are few studies of outcome in male patients with undefined 46 XY
      disorder of sex development (DSD). We aimed to assess testicular function and
      clinical characteristics after puberty in men with idiopathic 46 XY DSD. Design
      We conducted a University Hospital-based observational follow-up study. METHODS:
      Nineteen patients with severe hypospadias associated with other signs of
      defective virilization, such as microphallus, cryptorchidism, and/or bifid
      scrotum, who were initially managed during childhood between 1988 and 1994, were
      evaluated at a median age of 17.6 (16.3; 17.8) years. Outcome measures included
      clinical findings and serum testosterone, FSH, LH, and inhibin B concentrations.
      RESULTS: Testicular function was normal in only five (26%) patients. Impaired
      testicular function was observed in 14 (74%) patients and was partial (n=6; 32%)
      or total (n=8; 42%), requiring testosterone treatment for the initial (n=2) or
      secondary (n=6) induction of puberty. Undescended testis (unilateral n=3,
      bilateral n=2) was found and surgically managed only in the 14 patients with
      testicular impairment. Testosterone treatment in early childhood greatly
      increased penis length in all patients, but persistent microphallus following
      surgical treatment was observed at the end of puberty in most patients, with no
      difference between patients with and without testicular dysfunction (penis length
      of 68 (60; 75) vs 65 (60; 65) mm; P=0.42). Half the patients presented an adult
      height more than 5 cm below their target height. CONCLUSION: Men diagnosed with
      idiopathic 46 XY DSD during childhood are at high risk of testicular
      insufficiency and persistent micropenis, and this should be taken into account
      during the follow-up.

PMID- 21964960
TI  - GH deficiency in patients after cure of acromegaly by surgery alone.
AB  - OBJECTIVE: The aim of this study was to determine the frequency and
      characteristics of severe GH deficiency (sGHD) in patients after treatment of
      acromegaly by surgery alone. DESIGN AND METHODS: One hundred and eighty-six
      patients fulfilling the criteria for cure of acromegaly were examined by GH
      releasing peptide-2 stimulation test or arginine stimulation test as well as oral
      glucose tolerance test (GTT). In addition, the Japanese adult hypopituitarism
      questionnaire was completed to determine the quality of life (QoL). RESULTS: sGHD
      was found in 17 patients (9.1%; the GH-deficient group), and not found in 169
      patients (90.9%; the GH-sufficient group). There were no significant differences
      in preoperative serum GH levels, IGF1 levels, incidence of hyperprolactinemia,
      tumor volumes, or incidence of microadenoma between the two groups. Upon follow
      up examination, IGF1 levels and Z-scores of IGF1 levels were significantly lower
      in the GH-deficient group than in the GH-sufficient group, whereas neither basal
      GH levels nor nadir GH levels during 75 g GTT were significantly different
      between the two groups. Moreover, sGHD patients had a substantially higher
      incidence of multiple pituitary failures (17.6 vs 2.4%) and dyslipidemia (60 vs
      16.2%). sGHD patients had a substantially poorer condition-related QoL.
      CONCLUSIONS: This is the first large-scale, single-center, clinical study to
      evaluate sGHD in patients after cure of acromegaly by surgery alone. This study
      found that sGHD occurred in ~9% of patients and assessment of GHD by stimulation
      tests is critical after successful treatment of acromegaly by surgery.

PMID- 21964961
TI  - Current evidence for recommendation of surgery, medical treatment and vitamin D
      repletion in mild primary hyperparathyroidism.
AB  - Management of patients with mild primary hyperparathyroidism (PHPT) has been
      widely discussed because most patients today do not have specific symptoms. While
      surgery is always an option, the recommendations for treatment have shifted,
      which mostly reflects changes in clinical practice. In this study, we aimed to
      evaluate evidence for the current recommendations concerning operation vs
      observation, repletion with vitamin D (VitD) and alternative medical management.
      Surgery is followed by normalisation of calcium and parathyroid hormone (PTH) and
      a decrease in bone turnover followed by an increase in bone mass. It is not known
      what the consequences would be for the frequency of fractures. Randomised studies
      have indicated beneficial effects of operation on quality of life (QoL), but the
      effects have been minor and inconsistent. Operation seems not to be superior to
      observation for cardiovascular risk factors. Although PHPT patients in average
      have slightly decreased plasma 25OH VitD, severe symptomatic VitD deficiency
      seems not to be a characteristic of PHPT patients in Europe. However, if present,
      we recommend VitD substitution before final decision on surgical treatment. It is
      unknown whether routine VitD supplementation should be offered preoperatively to
      all patients with mild PHPT or as part of long-term medical treatment. Targeted
      medical management could be an option for patients with contraindications to
      surgery. Antiresorptive therapy might be appropriate for patients with a low bone
      mass to prevent further bone loss. Calcimimetics could be tried to control serum
      calcium levels although there is no evidence of an effect on the hypercalcaemic
      symptoms or the QoL. Combined therapy with calcimimetics and alendronate could be
      considered for patients with hypercalcaemia and overt bone disease.

PMID- 21964963
TI  - Decreased concentration of adiponectin together with a selective reduction of its
      high molecular weight oligomers is involved in metabolic complications of
      myotonic dystrophy type 1.
AB  - OBJECTIVE: The hormone adiponectin exerts beneficial pleiotropic effects on
      biological and metabolic processes. Although a well-recognized insulin
      sensitizer, its characteristic has yet to be clearly defined. Myotonic dystrophy
      type 1 (DM1) is a rare genetic disorder that features muscle wasting and
      metabolic comorbidity, and patients have an increased risk of developing type 2
      diabetes. We analyzed circulating levels of adiponectin and its oligomers to
      determine whether their expression correlates with metabolic alterations in DM1
      patients. DESIGN AND METHODS: We measured the anthropometric and biochemical
      features and three insulin resistance (IR) indices (homeostasis model assessment,
      quantitative insulin sensitivity check index, and McAuley) of 21 DM1 patients and
      of 82 age-, sex-, and weight-matched controls. In the blood samples of patients
      and controls, adiponectin levels were measured by ELISA, and its oligomers were
      characterized by using western blotting and gel filtration. The adiponectin gene
      was molecularly analyzed in patients. RESULTS: DM1 patients had significantly
      higher body mass index, waist circumference, triglycerides (TGs), glucose, tumor
      necrosis factor alpha, and IR; conversely, they had significantly lower
      concentrations of total serum adiponectin with a selective, pronounced decrease
      of its high molecular weight (HMW) oligomers. There was a strong negative
      correlation between adiponectin and TGs in DM1 patients. CONCLUSIONS: Our results
      endorse the hypothesis that decreased expression of adiponectin together with a
      selective reduction of its HMW oligomers contributes to the worsening of IR and
      its metabolic complications in DM1 patients. These findings suggest that
      adiponectin and HMW oligomers may serve as biomarkers and are promising
      therapeutic agents for IR and its consequences in DM1.

PMID- 21964964
TI  - N-heterocyclic carbene-catalyzed 1,3-dipolar cycloaddition reactions: a facile
      synthesis of 3,5-di- and 3,4,5-trisubstituted isoxazoles.
AB  - A first example of organo-N-heterocyclic carbene (NHC) catalyzed click-type fast
      1,3-dipolar cycloaddition of nitrile oxides with alkynes was developed for the
      regioselective synthesis of 3,5-di- and 3,4,5-trisubstituted isoxazoles.
      Triethylamine (Et(3)N) was employed as an effective base to generate both nitrile
      oxide and the organo-NHC catalyst in situ. This catalytic approach was used to
      attach a variety of substituents, including other biologically active fragments,
      onto the isoxazole ring to selectively design multinucleus structures. Further,
      we have also optimized the conditions for Cu(I)-free Sonogashira cross-coupling
      to obtain internal alkynes in high yields, which were subsequently used in
      cycloaddition. A catalytic cycle is proposed and the remarkable regiocontrol in
      the formation of isoxazoles was ascribed to a beneficial zwitterion intermediate
      developed by the interaction of the strongly nucleophilic organo-NHC catalyst
      with alkyne followed by nitrile oxide.

PMID- 21964962
TI  - Interaction between heavy smoking and CYP2A6 genotypes on type 2 diabetes and its
      possible pathways.
AB  - OBJECTIVE: To explore the interactions between smoking and CYP2A6 genotypes on
      type 2 diabetes (T2DM) as well as potential pathways for smoking in causing T2DM.
      DESIGN: Cross-sectional study. METHODS: A total of 1344 smokers with complete
      data from a community-based T2DM survey in Guangzhou and Zhuhai of China from
      July 2006 to June 2007 were interviewed with a structured questionnaire about
      socio-demographic status and daily cigarette consumption. Serum glucose, insulin,
      and cotinine were measured after an overnight fast. Subjects were genotyped for
      CYP2A6 and classified, according to genotype, into normal, intermediate, slow, or
      poor nicotine metabolizers based on prior knowledge of CYP2A6 allele associations
      with nicotine C-oxidation rate. Abdominal obesity was defined as a waist-to-hip
      ratio >=0.90 for males or >=0.85 for females. Type 2 diabetic patients (n=154)
      were diagnosed according to WHO 1999 criteria. Chi-square tests, multivariate
      logistic regression models, and a structural equation model were used in this
      study. RESULTS: Multivariate analysis indicated that, compared with light
      smoking, heavy smoking significantly increased the risk of T2DM (odds ratio
      (OR)=1.75, 95% CI=1.01-3.05). There were significant interactions between heavy
      smoking and slow CYP2A6 (OR=5.12, 95% CI=1.08-24.23) and poor CYP2A6 metabolizer
      genotypes (OR=8.54, 95% CI=1.28-57.02) on T2DM. Structural equation modeling
      indicated that CYP2A6 moderation of smoking quantity risk on T2DM was mediated by
      the effects on serum cotinine, abdominal obesity, insulin resistance, and insulin
      secretion. CONCLUSIONS: Heavy smoking was significantly associated with T2DM, and
      this association was moderated by CYP2A6 genotype and mediated by serum cotinine,
      abdominal obesity, insulin resistance, and insulin secretion.

PMID- 21964965
TI  - Safety review: dose optimization of somatostatin analogs in patients with
      acromegaly and neuroendocrine tumors.
AB  - INTRODUCTION: Patients with either acromegaly or neuroendocrine tumors (NET) can
      be treated with somatostatin analogs to relieve symptoms and improve disease
      control. However, there is an absence of large clinical trials specifically
      designed to document the safety when increases in somatostatin analog dosing are
      needed in patients who do not achieve their treatment goals. To fully explore and
      communicate any potential risks, we conducted a literature review and present a
      summary of the studies documenting the safety and tolerability of dose
      optimization with somatostatin analogs in patients with acromegaly and NET.
      METHODS: A literature search was undertaken to find clinical studies specifically
      reporting the effects of dose titration using the depot formulations of the
      somatostatin analogs, octreotide long-acting repeatable (LAR) or lanreotide, in
      patients with acromegaly and NET. RESULTS: Publications that described the
      treatment and management of patients with acromegaly and NET were reviewed. The
      rationale for dose optimization, including high-dose treatment in patients who
      are inadequately controlled on conventional doses and the safety and tolerability
      of somatostatin analogs, is discussed. CONCLUSION: A review of published clinical
      studies demonstrates that dose optimization provides additional biochemical
      control in patients with acromegaly and NET who are inadequately controlled with
      conventional starting doses of octreotide LAR and lanreotide ATG. The benefits of
      dose optimization include improved efficacy without a significant change in the
      recorded adverse events and the tolerability of the treatment. Therefore, patient
      response to treatment should be routinely monitored and their somatostatin analog
      dose increased or decreased thereafter according to their individual response.

PMID- 21964966
TI  - [Giant hamartoma of the lung].
AB  - Hamartomas are the most common benign tumors of the lungs and usually present as
      solitary intraparenchymal lesions a few centimeters in diameter which are
      detected radiologically as an incidental finding. This article reports on a case
      of a giant pulmonary hamartochondroma 29 cm in diameter, which impressed
      preoperatively and intraoperatively as an extrapulmonary neoplasm. The detection
      of smaller mesenchymal neoplastic lesions in the lungs and pleura is a further
      special feature of this case.

PMID- 21964967
TI  - The alimentary canal of the African lungfish Protopterus annectens during
      aestivation and after arousal.
AB  - We describe the structural modifications that occur in the alimentary canal of
      the African lungfish Protopterus annectens during aestivation and after arousal.
      With fasting, all gut segments undergo structural modifications. The epithelium
      covering the intestinal vestibule undergoes bursts of activation at 4 months of
      aestivation, adopting a more quiescent appearance at 6 months. The ridge area of
      the spiral intestine shows, at 4 months of aestivation, epithelial
      disintegration, cell desquamation, cell death, and loss of the freshwater
      phenotype. Surprisingly, the epithelium adopts a stratified appearance at 6
      months of aestivation. Except for epithelial disintegration, the smooth portion
      of the spiral intestine follows a similar pattern of modifications than the ridge
      area. The entire epithelium of spiral intestine appears to be renewed during
      aestivation. The presence of intraepithelial mast cells suggests that
      inflammation is part of the cellular response to aestivation. After arousal, cell
      phenotypes are restored in about 6 days, but full structural recovery is not
      attained during the experimental period (15 days post-aestivation). Several
      aspects of the cellular response to fasting are shared by a wide range of animal
      groups. This commonality agrees with the presence of a character that allows to
      adjust the structural and functional properties of the gut to food availability
      and food quality, and to the characteristics of the fasting episodes.

PMID- 21964968
TI  - Extraordinary metabolic stability of peptides containing alpha-aminoxy acids.
AB  - The metabolic stability of peptides containing a mixed sequence of alpha-aminoxy
      acids and alpha-amino acids is significantly improved compared to peptides
      composed of only natural alpha-amino acids. The introduction of an alpha-aminoxy
      acid into peptide chain dramatically improves the stability of the amide bonds
      immediately before and after it. These peptides containing alpha-aminoxy acids
      represent excellent structural scaffold for the design of metabolically stable
      and biologically active peptides.

PMID- 21964970
TI  - The progress of an American EHR-part 1.

PMID- 21964971
TI  - In the world of medical alphabet soup--"will a workable EMR or EHR please stand
      up?".

PMID- 21964972
TI  - Potential benefits of warfarin monitoring by a clinical pharmacist in a long term
      care facility.
AB  - The primary objective of this study was to determine whether warfarin therapy
      monitoring by a pharmacist would benefit a long-term care facility, by
      maintaining patients within therapeutic INR range more consistently than the
      current practice of physician monitoring.Secondary objectives included whether
      adverse events resulting from non-therapeutic INR levels differed significantly
      between groups and whether pharmacist interventions resulted in decreased overall
      costs to the facility. A retrospective chart review was conducted on all patients
      treated with warfarin for a minimum of 14 days within a Long-Term Care (LTC)
      facility to compare Time within Therapeutic Range (TTR) between staff treated
      patients versus pharmacist treated patients. A total of 552 INRs were obtained
      for all patients during the study period: 499 (90.4%) under staff supervision and
      53 (9.6%) under clinical pharmacist supervision. Of the 499 tests performed by
      the River Garden staff, 203 were within the desired range, compared with 29 of
      the 53 tests performed by the clinical pharmacist being in range. For the primary
      endpoint, a total of 1483 INRs were imputed, corresponding to the number of days
      between true INR measurements. INRs attributable to clinic staff management were
      within the therapeutic range 47.1% of the time, whereas INRs attributable to
      clinical pharmacist management were within the therapeutic range 58.7% of the
      time (P < 0.0001 for the comparison). Warfarin can be effectively monitored by a
      clinical pharmacist and routinely lead to appropriate INR levels in the nursing
      home setting, while potentially saving the facility healthcare dollars.

PMID- 21964973
TI  - Promiscuity in mice is associated with increased vaginal bacterial diversity.
AB  - Differences in the number of sexual partners (i.e., mating system) have the
      potential to exert a strong influence on the bacterial communities present in
      reproductive structures like the vagina. Because this structure serves as a
      conduit for gametes, bacteria present there may have a pronounced, direct effect
      on host reproductive success. As a first step towards the identification of the
      relationship between sexual behavior and potentially pathogenic bacterial
      communities inhabiting vital reproductive structures, as well as their potential
      effects on fitness, I sought to quantify differences in bacterial diversity in a
      promiscuous and monogamous mammal species. To accomplish this, I used two
      sympatric species of Peromyscus rodents--Peromyscus californicus and Peromyscus
      maniculatus that differ with regard to the number of sexual partners per
      individual to test the hypothesis that bacterial diversity should be greater in
      the promiscuous P. maniculatus relative to the monogamous P. californicus. As
      predicted, phylogenetically controlled and operational taxonomic unit-based
      indices of bacterial diversity indicated that diversity is greater in the
      promiscuous species. These results provide important new insights into the
      effects of mating system on bacterial diversity in free-living vertebrates, and
      may suggest a potential cost of promiscuity.

PMID- 21964969
TI  - Modeling paradigms for medical diagnostic decision support: a survey and future
      directions.
AB  - Use of computer based decision tools to aid clinical decision making, has been a
      primary goal of research in biomedical informatics. Research in the last five
      decades has led to the development of Medical Decision Support (MDS) applications
      using a variety of modeling techniques, for a diverse range of medical decision
      problems. This paper surveys literature on modeling techniques for diagnostic
      decision support, with a focus on decision accuracy. Trends and shortcomings of
      research in this area are discussed and future directions are provided. The
      authors suggest that-(i) Improvement in the accuracy of MDS application may be
      possible by modeling of vague and temporal data, research on inference
      algorithms, integration of patient information from diverse sources and
      improvement in gene profiling algorithms; (ii) MDS research would be facilitated
      by public release of de-identified medical datasets, and development of
      opensource data-mining tool kits; (iii) Comparative evaluations of different
      modeling techniques are required to understand characteristics of the techniques,
      which can guide developers in choice of technique for a particular medical
      decision problem; and (iv) Evaluations of MDS applications in clinical setting
      are necessary to foster physicians' utilization of these decision aids.

PMID- 21964974
TI  - Out of Africa: Fossils shed light on the origin of the hoatzin, an iconic
      Neotropic bird.
AB  - We describe the earliest fossils of the enigmatic avian taxon Opisthocomiformes
      (hoatzins) from the Oligo-Miocene (22-24 mya) of Brazil. The bones, a humerus,
      scapula and coracoid, closely resemble those of the extant hoatzin, Opisthocomus
      hoazin. The very similar osteology of the pectoral girdle in the new Brazilian
      fossil compared to the extant O. hoazin, in which it reflects peculiar feeding
      adaptations, may indicate that hoatzins had already evolved their highly
      specialized feeding behavior by the mid-Cenozoic. We further show that Namibiavis
      senutae from the early Miocene of Namibia is another, previously misclassified
      representative of Opisthocomiformes, which documents that the extant Neotropic
      distribution of hoatzins is relictual. Because of the weak flight capabilities of
      hoatzins, their occurrence on both sides of the South Atlantic is of particular
      biogeographic interest. We detail that this distribution pattern is best
      explained by dispersal from Africa to South America, and that Opisthocomiformes
      provide the first example of transatlantic rafting among birds.

PMID- 21964975
TI  - Longitudinal effects of SafeTalk, a motivational interviewing-based program to
      improve safer sex practices among people living with HIV/AIDS.
AB  - Programs to help people living with HIV/AIDS practice safer sex are needed to
      prevent transmission of HIV and other sexually transmitted infections. We sought
      to assess the impact of SafeTalk, a multicomponent motivational interviewing
      based safer sex program, on HIV-infected patients' risky sexual behavior. We
      enrolled sexually active adult HIV-infected patients from one of three clinical
      sites in North Carolina and randomized them to receive the 4-session SafeTalk
      intervention versus a hearthealthy attention-control. There was no significant
      difference in the proportion of people having unprotected sex between the two
      arms at enrollment. SafeTalk significantly reduced the number of unprotected sex
      acts with at-risk partners from baseline, while in controls the number of
      unprotected sex acts increased. Motivational interviewing can provide an
      effective, flexible prevention intervention for a heterogeneous group of people
      living with HIV.

PMID- 21964976
TI  - Partner characteristics and undiagnosed HIV seropositivity among men who have sex
      with men only (MSMO) and men who have sex with men and women (MSMW) in Baltimore.
AB  - This study examined the relationship between HIV risk behaviors, partner
      characteristics, and undiagnosed seropositivity among men who have sex with men
      and women (MSMW) and men who have sex with men only (MSMO). BESURE-MSM2 is a
      venue-based cross-sectional HIV surveillance study conducted among MSM in 2008.
      Stratified log-binomial regression was used to assess adjusted prevalence ratios
      of undiagnosed seropositivity among 103 MSMW and 296 MSMO (N = 399). Among MSMO,
      race/ethnicity, age, having had a sexually transmitted infection, concurrency,
      and having a black/African American male partner were associated with undiagnosed
      seropositivity. Among MSMW, having five or more male partners, having a main male
      partner, and having a main female partner were associated with undiagnosed
      seropositivity. Our findings underscore the importance of partner characteristics
      in understanding HIV transmission. HIV programs for men with both male and female
      partners are needed to address the unique partnership dynamics of MSMW.

PMID- 21964977
TI  - Stigma and sexual compulsivity in a community-based sample of HIV-positive gay
      and bisexual men.
AB  - A better exploration of factors associated with sexual compulsivity (SC) among
      various subpopulations may help to explain its etiology, development, and course,
      as well as provide implications for treatment. Criticisms of SC highlight the
      need to have a better understanding of SC that takes into account both behavioral
      and psychosocial variables such as stigma, particularly stigma related to sexual
      orientation and HIV status. The purpose of this study was to investigate the
      association of SC with sexual behavior and stigma in a sample of HIV-positive gay
      and bisexual men. A cross-sectional, street-intercept method was adapted to
      survey a sample of 127 HIV-positive gay and bisexual males at two large-scale
      LGBT community events in the fall of 2008 and spring of 2009. We found that the
      number of recent male sexual partners (AOR = 1.05) and internalized HIV stigma
      (AOR = 8.20) were significantly associated with SC symptomology, while
      internalized homonegativity and interpersonal HIV stigma were not. These findings
      contradict many prominent criticisms of SC while highlighting the need to better
      understand the mechanisms related to the development of SC symptomology and the
      potential role stigma may have for the psychosexual well-being of HIV-positive
      gay and bisexual men.

PMID- 21964978
TI  - Phenotypic heterogeneity in Woodhouse-Sakati syndrome: two new families with a
      mutation in the C2orf37 gene.
AB  - Hypogonadism, alopecia, diabetes mellitus, mental retardation, and extrapyramidal
      syndrome [also known as Woodhouse-Sakati syndrome (WSS)] is a rare autosomal
      recessive neuroendocrine and ectodermal disorder. The syndrome was first
      described by Woodhouse and Sakati in 1983, and 47 patients from 23 families have
      been reported so far. We report on an additional seven patients (four males and
      three females) from two highly consanguineous Arab families from Qatar,
      presenting with a milder phenotype of WSS. These patients show the spectrum of
      clinical features previously found in WSS, but lack evidence of diabetes mellitus
      and extrapyramidal symptoms. These two new families further illustrate the
      natural course and the interfamilial phenotypic variability of WSS that may lead
      to challenges in making the diagnosis. In addition, our study suggests that WSS
      may not be as infrequent in the Arab world as previously thought.

PMID- 21964980
TI  - Surveillance of suspected adverse reactions to herbal products used as laxatives.
AB  - AIM: To describe and evaluate spontaneous reports of suspected adverse reactions
      (ARs) associated with herbal laxatives received by the Italian Medicines Agency
      and the Italian National Institute of Health between April 2002 and January 2011.
      METHODS: Spontaneous reports of suspected ARs were individually analyzed by a
      multidisciplinary group of experts, and a causality assessment was performed.
      RESULTS: Twenty-six reactions were reported during the study period. Of these,
      eight were associated with herbal medicinal products and 18 were related to
      herbal food supplements. Almost 80% of the reports on ARs involved women. The
      ARs, classified by System Organ Class, were associated with gastrointestinal,
      skin and subcutaneous tissue, and hepatobiliary disorders. Fifty percent of the
      reactions were serious, with the patients requiring hospitalization; of these,
      one was life-threatening. Most of the herbal remedies associated with the
      reported ARs contained liquorice, dandelion, and/or plants containing
      anthraquinones. Possible causes of the ARs were long-term use, idiosyncratic
      reactions or hypersensitivity, and interaction with other treatments. All of
      these factors and the presence of a large number of components in the same
      product increased the unpredictability of the final effect. CONCLUSIONS: The
      total number of 26 ARs recorded in 8 years is limited; however, the an under
      reporting effect cannot be excluded. Moreover, taking into account the
      seriousness of the reported ARs, the low number of reports does not represent a
      guarantee of safety. To reduce the risk of an adverse outcome, herbal laxatives
      should be used only over the short term.

PMID- 21964979
TI  - Local disruption of glial adenosine homeostasis in mice associates with focal
      electrographic seizures: a first step in epileptogenesis?
AB  - Astrogliosis and associated dysfunction of adenosine homeostasis are pathological
      hallmarks of the epileptic brain and thought to contribute to seizure generation
      in epilepsy. The authors hypothesized that astrogliosis-an early component of the
      epileptogenic cascade-might be linked to focal seizure onset. To isolate the
      contribution of astrogliosis to ictogenesis from other pathological events
      involved in epilepsy, the authors used a minimalistic model of epileptogenesis in
      mice, based on a focal onset status epilepticus triggered by intra-amygdaloid
      injection of kainic acid. The authors demonstrate acute neuronal cell loss
      restricted to the injected amygdala and ipsilateral CA3, followed 3 weeks later
      by focal astrogliosis and overexpression of the adenosine-metabolizing enzyme
      adenosine kinase (ADK). Using synchronous electroencephalographic recordings from
      multiple depth electrodes, the authors identify the KA-injected amygdala and
      ipsilateral CA3 as two independent foci for the initiation of non-synchronized
      electrographic subclinical seizures. Importantly, seizures remained focal and
      restricted to areas of ADK overexpression. However, after systemic application of
      a non-convulsive dose of an adenosine A(1) -receptor antagonist, seizures in
      amygdala and CA3 immediately synchronized and spread throughout the cortex,
      leading to convulsive seizures. This focal seizure phenotype remained stable over
      at least several weeks. We conclude that astrogliosis via disruption of adenosine
      homeostasis per se and in the absence of any other overt pathology, is associated
      with the emergence of spontaneous recurrent subclinical seizures, which remain
      stable over space and time. A secondary event, here mimicked by brain-wide
      disruption of adenosine signaling, is likely required to turn pre-existing
      subclinical seizures into a clinical seizure phenotype.

PMID- 21964981
TI  - MTDH and EphA7 are markers for metastasis and poor prognosis of gallbladder
      adenocarcinoma.
AB  - Gallbladder cancer is an aggressive cancer with extremely poor prognosis. Over
      90% of patients are diagnosed at an advanced, inoperable stage with metastasis
      and invasion to other organs. In this study, the expression of metadherin (MTDH)
      and erythropoietin-producing hepatoma-amplified sequence (Eph) receptor A7
      (EphA7) in 96 benign and 108 malignant lesions of gallbladder was determined by
      immunohistochemistry, and their correlations with pathological features and
      prognosis were analyzed. Positive expression of EphA7 and MTDH was significantly
      higher in gallbladder adenocarcinoma than in benign lesions. In adenocarcinoma,
      the positive expression of EphA7 and MTDH was significantly associated with
      differentiation, tumor mass, lymphnode metastasis, invasion, and overall
      survival. Multivariate Cox regression analysis suggested that positive expression
      of EphA7 and MTDH was an independent poor-prognostic predictor in gallbladder
      adenocarcinoma. The elevated expression of EphA7 and/or MTDH is closely related
      to carcinogenesis, progression, clinical biological behaviors, and prognosis of
      gallbladder adenocarcinoma.

PMID- 21964982
TI  - Efficacy of radiosynovectomy in rheumatoid arthritis.
AB  - In this retrospective study, we evaluated the effect of radiosynovectomy of
      patients with rheumatoid arthritis. Radiosynovectomy was performed in 577 joints
      of 137 rheumatoid patients. We applied 185 MBq yttrium-90 in knees (n = 58), 74
      111 MBq rhenium-186 colloids in ankle (n = 50), wrists (n = 43) and shoulders (n
      = 35), and 15 to 37 MBq in finger (n = 298) and toe joints (n = 46). The effect
      of radiosynovectomy was scored in 4 subjective categories: excellent response (no
      symptoms); good response (significant reduction of symptoms); moderate response
      (slight decrease); and bad response (no change or worsening), of pain and/or
      swelling in treated joint 3 months after the procedure. Excellent or good
      response was observed in 57% of treated knees, 63% of shoulders, 60% of wrists,
      64% of ankles, 54% of thumb bases, 55% of MCP's, 54% of PIP's, 53% of DIP's, and
      54% of MTP's. Side effects associated to the RSO, i.e., swelling or transient
      increase of pain, were recorded in 7% of the patients that resolved within 1
      month. No patient had any non-reversible skin alteration after treatment, only
      slight erythema was observed in 5 patients. Radiosynovectomy is effective and
      safe in the treatment of rheumatoid arthritis.

PMID- 21964983
TI  - Lifetime history of depression, type 2 diabetes, and endothelial reactivity to
      acute stress in postmenopausal women.
AB  - BACKGROUND: Coronary heart disease is a major cause of mortality in women and
      persons with diabetes. Mental stress and major depressive disorder have both been
      associated with coronary heart disease. Endothelial functioning is a clinically
      meaningful manifestation of CHD that is detectable in its earliest stages.
      PURPOSE: This study aims to determine whether acute stress and lifetime history
      of major depressive disorder are associated with functional and biochemical
      markers of endothelial function and whether this relationship varies by diabetes
      status. METHODS: Resting endothelial function was assessed for n = 215
      postmenopausal women with no known or suspected coronary artery disease
      participated. Of these, 108 had a positive lifetime major depressive disorder (L
      MDD; assessed through structured clinical interview) and had been free of major
      depressive disorder for >6 months; 103 had type 2 diabetes. Endothelial
      reactivity to acute mental stress was assessed for n = 114 of the participants.
      Endothelial function was assessed by flow-mediated dilation of the brachial
      artery (FMD) by total plasma nitrite, the cumulative molecule from nitric oxide
      (NO) generation, and by plasma endothelin-1 (ET-1). RESULTS: Participants with L
      MDD had lower NO and lower FMD compared to never-depressed controls. Secondary
      analyses suggest that among participants with L-MDD, antidepressant medications
      are associated with higher NO. Participants with diabetes had higher NO but lower
      FMD than nondiabetic controls. Mental stress affected FMD in the entire sample.
      Diabetes moderated the effect of mental stress on NO and L-MDD moderated the
      effect of mental stress on ET-1. CONCLUSIONS: History of depression, even in full
      remission, is associated with impaired endothelial functioning regardless of
      diabetes status. Acute mental alters FMD, NO, and ET-1 differentially among
      subgroups.

PMID- 21964984
TI  - Purification and identification of antioxidant peptides from egg white protein
      hydrolysate.
AB  - Egg white proteins were hydrolysed separately using five different proteases to
      obtain antioxidant peptides. The antioxidant activity of egg white protein
      hydrolysates was influenced by the time of hydrolysis and the type of enzyme. Of
      the various hydrolysates produced, papain hydrolysate obtained by 3-h hydrolysis
      (PEWPH) displayed the highest DPPH radical scavenging activity. PEWPH could also
      quench the superoxide anion and hydroxyl radicals, effectively inhibit lipid
      peroxidation and exhibit reducing power. Then, PEWPH was purified sequentially by
      ultrafiltration, gel filtration, RP-HPLC and two fractions with relatively strong
      antioxidant activity were subsequently subjected to LC-MS/MS for peptide sequence
      identification. The sequences of the two antioxidant peptides were identified to
      be Tyr-Leu-Gly-Ala-Lys (551.54 Da) and Gly-Gly-Leu-Glu-Pro-Ile-Asn-Phe-Gln
      (974.55 Da), and they were identified for the first time from food-derived
      protein hydrolysates. Last, the two purified peptides were synthesized and they
      showed 7.48- and 6.02-fold higher DPPH radical scavenging activity compared with
      the crude PEWPH, respectively. These results indicate that PEWPH and/or its
      isolated peptides may be useful ingredients in food and nutraceutical
      applications.

PMID- 21964985
TI  - Congenital nasal obstruction: clinical and radiologic review.
AB  - Congenital nasal obstruction can result in neonatal respiratory distress because
      neonates are obligate nasal breathers. Therefore, all physicians who deal with
      infants should be familiar with the structural abnormalities, masses, and
      syndromes that cause nasal obstruction, so that appropriate work-up and treatment
      can be promptly initiated. This paper reviews the embryology of the nasal passage
      and then continues with the different causes of nasal obstruction. Special
      attention is paid to the presentation, physical exam findings, and imaging
      modality of choice.

PMID- 21964987
TI  - Abstracts of XXXVIII Annual ESAO and IV Biennial IFAO Congress, 9-12 October
      2011, Porto, Portugal.

PMID- 21964986
TI  - On the effect of prospective payment on local hospital competition in Germany.
AB  - The introduction of prospective hospital reimbursement based on diagnosis related
      groups (DRG) in 2004 has been a conspicuous attempt to increase hospital
      efficiency in the German health sector. As a consequence of the reform a rise of
      competition for (low cost) patients could be expected. In this paper the
      competition between hospitals, quantified as spatial spillover estimates of
      hospital efficiency, is analyzed for periods before and after the reform. We
      implement a two-stage efficiency model that allows for spatial interdependence
      among hospitals. Hospital efficiency is determined by means of non-parametric and
      parametric econometric frontier models. We diagnose a significant increase of
      negative spatial spillovers characterizing hospital performance in Germany, and
      thus, confirm the expected rise of competition.

PMID- 21964988
TI  - Strongyloides stercoralis in bronchoalveolar lavage specimen processed as
      Prussian Blue Stain.
AB  - Strongyloidiasis is an infectious disease caused by the nematode helminth,
      Strogyloides stercoralis. Subjects immunosuppressed, immunocomprised, or on
      steroids are susceptible to hyperinfection and dissemination. Early detection of
      parasitic infection in such individuals is extremely important as disseminated
      Strongyloidiasis is potentially fatal. Here, we present a case of
      Strongyloidiasis initially detected by Prussian blue stain of bronchoalveolar
      lavage (BAL) specimen from an immunosuppressed patient who was treated with
      prednisone for acute interstitial nephritis and developed hemoptysis.

PMID- 21964990
TI  - Implementation and development of federally-funded systems of care over time.
AB  - This study describes development in federally funded systems of care. Data for
      this study were collected using the System of Care Assessment that rated
      grantees' enactment of system of care principles in the infrastructure and
      service delivery domains. Data were collected by trained raters who conducted
      several site visits over the funding period. This study described system
      development over time across 61 sites and tested whether gains were statistically
      significant. Latent profile analysis was used to explore whether sites could be
      meaningfully grouped based on their baseline service delivery domain scores.
      Differences across groups were tested in terms of community, system, and client
      characteristics. Differential growth across groups was also examined. Overall,
      systems of care developed over time in both the infrastructure and service
      delivery domains. Although infrastructure scores were generally lower than
      service delivery scores, greater gains were seen for the infrastructure domain.
      Three groups of sites were identified that could be distinguished in terms of
      degree of development overall, and for specific system of care principles. The
      groups of sites differed in terms of community factors, system features, and
      client characteristics. In addition, repeated measures analyses found
      differential growth in system development over time across groups.

PMID- 21964989
TI  - Neurogenic detrusor overactivity in patients with spinal cord injury: evaluation
      and management.
AB  - Lower urinary tract dysfunction can have a significant impact on patients with
      spinal cord injury. Over the years, many treatment options have become available.
      This article reviews the assessment and management of neurogenic detrusor
      overactivity, with a particular focus on articles from the recent literature.
      Recent guidelines on the subject will be discussed. Management options include
      antimuscarinics and bladder emptying measures, botulinum toxin A, and
      neuromodulation in refractory cases and surgery for intractable cases. Recent and
      relevant publications in these areas will be summarized and discussed.

PMID- 21964993
TI  - Response to imazapyr and dominance relationships of two imidazolinone-tolerant
      alleles at the Ahasl1 locus of sunflower.
AB  - Imisun and CLPlus are two imidazolinone (IMI) tolerance traits in sunflower
      (Helianthus annuus L.) determined by the expression of different alleles at the
      same locus, Ahasl1-1 and Ahasl1-3, respectively. This paper reports the level of
      tolerance expressed by plants containing both alleles in a homozygous,
      heterozygous and in a heterozygous stacked state to increasing doses of IMI at
      the enzyme and whole plant levels. Six genotypes of the Ahasl1 gene were compared
      with each other in three different genetic backgrounds. These materials were
      treated at the V2-V4 stage with increasing doses of imazapyr (from 0 to 480 g
      a.i. ha(-1)) followed by an assessment of the aboveground biomass and herbicide
      phytotoxicity. The estimated dose of imazapyr required to reduce biomass
      accumulation by 50% (GR(50)) differed statistically for the six genotypes of the
      Ahasl1 gene. Homozygous CLPlus (Ahasl1-3/Ahasl1-3) genotypes and materials
      containing a combination of both tolerant alleles (Imisun/CLPlus heterozygous
      stack, Ahasl1-1/Ahasl1-3) showed the highest values of GR(50), 300 times higher
      than the susceptible genotypes and more than 2.5 times higher than homozygous
      Imisun materials (Ahasl1-1/Ahasl1-1). In vitro AHAS enzyme activity assays using
      increasing doses of herbicide (from 0 to 100 MUM) showed similar trends, where
      homozygous CLPlus materials and those containing heterozygous stacks of
      Imisun/CLPlus were statistically similar and showed the least level of inhibition
      of enzyme activity to increasing doses of herbicide. The degree of dominance for
      the accumulation of biomass after herbicide application calculated for the Ahasl1
      1 allele indicated that it is co-dominant to recessive depending on the imazapyr
      dose used. By the contrary, the Ahasl1-3 allele showed dominance to semi
      dominance according to the applied dose. This last allele is dominant over Ahasl1
      1 over the entire range of herbicide rates tested. At the level of enzymatic
      activity, however, both alleles showed recessivity to semi-recessivity with
      respect to the wild-type allele, even though the Ahasl1-3 allele is dominant over
      Ahasl1-1 at all the herbicides rates used.

PMID- 21964994
TI  - Analysis of survival and prognostic factors of pediatric patients with brain
      tumor.
AB  - OBJECTIVES: To estimate survival and evaluate prognostic factors of pediatric
      patients with central nervous system (CNS) tumors treated in a single center.
      METHODS: Retrospective analysis of survival of 103 children with primary brain
      tumors diagnosed consecutively from January 2000 to December 2006. Cox regression
      was used for multivariate analysis of factors that affect overall survival to
      define possible prognostic factors. RESULTS: Median and mean ages were 7.2 and
      7.6 years. There was a male predominance (1.22:1). Most patients had
      medulloblastomas or primitive neuroectodermal tumors (PNET, 38%), or low-grade
      astrocytomas (18%). The anatomic site of most tumors was the cerebellum (49%) and
      the brain stem (21%). Five-year survival after diagnosis was 84% for low-grade
      astrocytomas and 51% for medulloblastomas and PNET. Prognostic factors for
      overall survival were histopathological type (high-grade astrocytomas and
      ependymomas; hazard ratio = 3.7 to 3.9), surgery (hazard ratio of 0.5 for
      completely resected tumors) and radiotherapy (hazard ratio of 0.5 for patients
      who underwent radiotherapy). CONCLUSIONS: Overall survival of pediatric patients
      with brain tumors in this study was similar to that found in populations of the
      United States and Europe. The prognostic factors defined for overall survival are
      also similar to those published in previous studies.

PMID- 21964995
TI  - Angelman syndrome and prenatally diagnosed Prader-Willi syndrome in first
      cousins.
AB  - Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are caused by loss of
      function of imprinted genes in the 15q11-13 critical region. Reports of PWS and
      AS in close relatives within the same family are rare. We report on the diagnosis
      of a familial unbalanced 10;15 translocation causing AS in a child that led to
      the prenatal diagnosis of an unbalanced 10;15 translocation with resultant
      deletion of the Prader-Willi critical region in her maternal uncle's offspring.

PMID- 21964997
TI  - Coping with serious events at work: a study of traumatic stress among nurses.
AB  - BACKGROUND: Nurses often encounter serious events during their work, which can
      lead to traumatic stress. OBJECTIVE: To examine how serious events, demographic
      variables, and coping strategies are associated with traumatic stress in a sample
      of nurses working in the medical department of a university teaching hospital.
      DESIGN: The data for this survey were collected in 2003. Two questionnaires were
      completed by nurses: the Utrecht Coping List (UCL) and the List of Serious Events
      and Traumatic Stress in Nursing (Nursing LIST). RESULTS: The 69 nurses who
      participated in the study had experienced a mean of 8 serious events in the past
      5 years. In all, 98% of all nurses reported traumatic stress. Active coping,
      social support, and comforting cognitions were independently associated with
      traumatic stress. CONCLUSION: The participating nurses had experienced multiple
      serious events, and many felt traumatized. Active coping decreased the risk of
      experiencing traumatic stress, whereas comforting cognitions and social support
      increased the likelihood of appraising a serious event as traumatic. More
      research needs to be conducted to support these findings and to develop
      strategies to support nurses after serious events.

PMID- 21964996
TI  - Non-linear mixed effects modeling of antiretroviral drug response after
      administration of lopinavir, atazanavir and efavirenz containing regimens to
      treatment-naive HIV-1 infected patients.
AB  - The objective of this analysis was to compare three methods of handling HIV-RNA
      data below the limit of quantification (LOQ) when describing the time-course of
      antiretroviral drug response using a drug-disease model. Treatment naive
      Scandinavian HIV-positive patients (n = 242) were randomized to one of three
      study arms. Two nucleoside reverse transcriptase inhibitors were administrated in
      combination with 400/100 mg lopinavir/ritonavir twice daily, 300/100 mg
      atazanavir/ritonavir once a day or 600 mg efavirenz once a day. The viral
      response was monitored at screening, baseline and at 1, 2, 3, 4, 12, 24, 48, 96,
      120, and 144 weeks after study initiation. Data up to 400 days was fitted using a
      viral dynamics non-linear mixed effects drug-disease model in NONMEM. HIV-RNA
      data below LOQ of 50 copies/ml plasma (39%) was omitted, replaced by LOQ/2 or
      included in the analysis using a likelihood-based method (M3 method). Including
      data below LOQ using the M3 method substantially improved the model fit. The drug
      response parameter expressing the fractional inhibition of viral replication was
      on average (95% CI) estimated to 0.787 (0.721-0.864) for lopinavir and atazanavir
      treatment arms and 0.868 (0.796-0.923) for the efavirenz containing regimen. At
      400 days after treatment initiation 90% (76-100) of the lopinavir and atazanavir
      treated patients were predicted to have undetectable viral levels and 96% (89
      100%) for the efavirenz containing treatment. Including viral data below the LOQ
      rather than omitting or replacing data provides advantages such as better model
      predictions and less biased parameter estimates which are of importance when
      quantifying antiretroviral drug response.

PMID- 21964998
TI  - The effect of an inpatient transition intervention on attendance at the first
      appointment postdischarge from a psychiatric hospitalization.
AB  - BACKGROUND: Only 42% of initial appointments following psychiatric
      hospitalization are kept nationally. Missed appointments increase the likelihood
      of rehospitalization and increase costs of outpatient care. OBJECTIVE: This study
      explored the feasibility, outcomes, and cost of a transition intervention on
      attendance at the first postdischarge appointment. DESIGN: A pilot study using a
      one-group prospective design interviewed 15 patients hospitalized with psychosis
      to address potential barriers to attendance at the first postdischarge
      appointment. Patients also identified an agenda for this appointment and received
      a reminder letter. RESULTS: Twelve (92%) of 13 patients attended the
      postdischarge appointment compared with the previous rate of 44%. Two additional
      patients were unable to attend because they had been rehospitalized before the
      scheduled time of the first appointment. DISCUSSION: Contact with a clinician who
      can bridge the gap between discharge and the first postdischarge appointment is
      feasible and may be helpful in increasing attendance rates.

PMID- 21964999
TI  - Changes in diurnal salivary cortisol levels in response to an acute stressor in
      healthy young adults.
AB  - BACKGROUND: Knowledge of the diurnal cortisol response to acute stress in healthy
      individuals can help us better understand the physiological and health effects of
      chronic stress. OBJECTIVE: To compare the diurnal patterns of cortisol secretion
      of 15 medical students 2 weeks before a major written examination (control phase)
      and 2 weeks later at the time of the examination (acute stress phase). DESIGN:
      Interrupted time series within-subjects. RESULTS: During the acute stress phase,
      less cortisol was secreted over the course of the day, as demonstrated by a more
      prolonged and steeper decline in cortisol levels. In addition, higher cortisol
      levels were present in the evening. Despite these changes in the usual diurnal
      pattern, overall exposure to cortisol remained the same for both phases.
      CONCLUSIONS: The results of this study suggest that specific adaptations to the
      diurnal pattern of cortisol are made in the face of acute stress, important
      information for understanding cortisol regulation in health and illness.

PMID- 21965000
TI  - A clinical translation of the research article titled "changes in diurnal
      salivary cortisol levels in response to an acute stressor in healthy young
      adults".

PMID- 21965001
TI  - Psychiatric mental health registered nurses (RN-PMHs): the key to patient safety
      and recovery-oriented care in acute psychiatric settings.

PMID- 21965002
TI  - Lessons learned: providing access through simulation.

PMID- 21965003
TI  - Behind the door: simulated crises implemented in psychiatric/mental health
      nursing education.

PMID- 21965005
TI  - Differential gene induction in resistant and susceptible potato cultivars at
      early stages of infection by Phytophthora infestans.
AB  - Sarpo Mira, a potato variety with high resistance against the late blight
      pathogen Phytophthora infestans, is being used in breeding programs to increase
      late blight resistance in commercial varieties. Discovering genes that are
      important for P. infestans resistance will assist in the development of molecular
      markers for the selection of new resistant cultivars and the use of resistant
      varieties will reduce the environmental, health and financial costs associated
      with the use of pesticides. Using complementary DNA amplified fragment length
      polymorphism analyses, differentially expressed genes involved in the potato-P.
      infestans interaction were identified in the susceptible Bintje and in the
      resistant Sarpo Mira potato cultivars. Forty-eight differentially expressed
      transcript derived fragments (TDFs) were cloned and sequenced. The expression
      profiles of some of these genes were analyzed in detail using quantitative RT-PCR
      at seven time points: 1, 4, 17, 24, 30, 41 and 65 hours after inoculation (hai).
      We found that five transcripts with homologies to pathogenesis/defense-related
      genes and two TDFs with homology to transcription factors were significantly
      induced to higher levels in the resistant cultivar at very early stages of the
      infection (1 hai). Interestingly, most of these genes showed different expression
      profiles throughout the whole infection process between both cultivars.
      Particularly during its biotrophic growth phase, P. infestans triggered the down
      regulation of infection responsive genes in the susceptible but not in the
      resistance cultivar. Our results suggest that these newly identified early
      induced transcripts may be good candidates for conferring Sarpo Mira's resistance
      to late blight and they could be useful molecular markers for the selection of
      new resistant cultivars.

PMID- 21965006
TI  - There is no way to identify patients who will harbor small volume, unilateral
      prostate cancer at final pathology. implications for focal therapies.
AB  - BACKGROUND: The aim of this study was to assess the clinical characteristics of
      the potentially ideal candidates for focal therapy, that is, patients with
      unilateral, small volume (namely, pT2a) prostate cancer (PCa) at radical
      prostatectomy (RP). MATERIALS AND METHODS: We evaluated 2,503 consecutive pT2 PCa
      patients treated with RP between 2002 and 2009 at a single center. Within this
      population, the clinical characteristics of patients with pT2a and pT2b/c disease
      were compared. Univariable and multivariable logistic regression models were
      fitted to assess clinical predictors of pT2a at RP. RESULTS: Overall, 349
      patients (14%) had pT2a PCa, while the remaining patients had either pT2b (n =
      334; 15.5%) or pT2c disease (n = 1,820 patients; 84.5%). Patients with pT2a PCa
      had a significantly lower mean PSA value, lower mean percentage of positive
      biopsy cores and lower biopsy Gleason score distribution (all P <= 0.03).
      However, at multivariable analyses, only percentage of positive cores maintained
      an independent predictor status (P = 0.01). Even when considering only patients
      sharing all the most favorable PCa characteristics (namely, clinical stage T1,
      PSA <= 4, Gleason score <=6 and percentage of positive cores <=25%), the rate of
      pT2a disease was only 24%. CONCLUSIONS: The rate of small volume, unilateral PCa
      even among patients with extremely favourable PCa characteristics was remarkably
      low (roughly 25%). This suggests that: (1) Three quarters of the best candidates
      for focal therapy would ultimately show adverse pathological features; (2) At
      present, accurate identification of the ideal candidate for focal therapy is not
      possible with current clinical-pathologic parameters.

PMID- 21965004
TI  - Role of cell cycle re-entry in neurons: a common apoptotic mechanism of neuronal
      cell death.
AB  - Currently, there is no effective treatment for neurodegenerative disorders such
      as Alzheimer's disease and Parkinson's disease. Thus, a major focus of
      neuroscience research is to examine the mechanisms involved in neuronal loss in
      order to identify potential drug targets. Recent results indicate that DNA damage
      and re-entry into the cell cycle may constitute a common pathway in apoptosis in
      neurological diseases. The role of the cell cycle in such disorders is supported
      by data on the brain of patients who showed an increase in cell-cycle protein
      expression. Indeed, studies performed in neuronal cell preparations indicate that
      oxidative stress could be the main mechanism responsible for cell cycle re-entry.
      DNA damage and repair after oxidative stress may activate the enzyme ataxia
      telangiectasia mutated, which is a cell-cycle regulator. Once the cell cycle is
      activated, the increase in the expression of transcription factor E2F-1 could
      induce neuronal apoptosis. Furthermore, the potential routes involved in E2F-1
      induced apoptosis could be p53-dependent or p53-independent. Under this E2F-1
      hypothesis of cell death, multiple mitochondria-dependent pathways may be
      activated, including caspase and caspase-independent signaling cascades. Finally,
      given that cyclin-dependent kinase inhibitory drugs have neuroprotective and anti
      apoptotic effects in experimental models, their potential application for the
      treatment of neurological disorders should be taken into account.

PMID- 21965007
TI  - Genomic instability in blood cells from murine model of mucopolysaccharidosis
      type I.
AB  - Mucopolysaccharidosis type I (MPS I) is caused by a deficiency of alfa
      iduronidase (IDUA), which leads to intralysosomal accumulation of
      glycosaminoglycans. Some studies have revealed that oxidative stress plays an
      important role in MPS I. However, the mechanisms by which these alterations occur
      are still not fully understood. The aim of this study was to analyze genomic
      instability in blood cells from murine model of MPS I by single cell gel (comet)
      assay and micronucleus test. The results pointed out genetic damage in blood
      cells as depicted by the single cell gel (comet) assay results. By contrast, no
      increase of micronucleated cells were found in mouse blood cells when compared to
      negative control. Taken together, our results suggest that IDUA deficiency
      induces genomic damage in blood cells. Certainly, this finding offers new
      insights into the mechanisms underlying the relation between IDUA deficiency and
      clinical manifestations that can occur in MPS I patients.

PMID- 21965008
TI  - The missing link between smoking and COPD autoreactivity?

PMID- 21965009
TI  - Thank God it's Friday!: achieving balance between continuity of care and
      intensivist burnout.

PMID- 21965010
TI  - The effect of insurance status on mortality and procedure use in critically ill
      patients: an object lesson in financial incentives.

PMID- 21965011
TI  - The importance of imaging in cystic fibrosis.

PMID- 21965012
TI  - Psychological stress: a social pollutant that may enhance environmental risk.

PMID- 21965013
TI  - Semi-long-term mortality effects of ozone.

PMID- 21965015
TI  - Oxidative stress-induced antibodies to carbonyl-modified protein correlate with
      severity of chronic obstructive pulmonary disease.
AB  - RATIONALE: There is increasing evidence for the presence of autoantibodies in
      chronic obstructive pulmonary disease (COPD). Chronic oxidative stress is an
      essential component in COPD pathogenesis and can lead to increased levels of
      highly reactive carbonyls in the lung, which could result in the formation of
      highly immunogenic carbonyl adducts on "self" proteins. OBJECTIVES: To determine
      the presence of autoantibodies to carbonyl-modified protein in patients with COPD
      and in a murine model of chronic ozone exposure. To assess the extent of
      activated immune responses toward carbonyl-modified proteins. METHODS: Blood and
      peripheral lung were taken from patients with COPD, age-matched smokers, and
      nonsmokers with normal lung function, as well as patients with severe persistent
      asthma. Mice were exposed to ambient air or ozone for 6 weeks. Antibody titers
      were measured by ELISA, activated compliment deposition by immunohistochemistry,
      and cellular activation by ELISA and fluorescence-activated cell sorter.
      MEASUREMENTS AND MAIN RESULTS: Antibody titer against carbonyl-modified self
      protein was significantly increased in patients with Global Initiative for
      Chronic Obstructive Lung Disease stage III COPD compared with control subjects.
      Antibody levels inversely correlated with disease severity and showed a
      prevalence toward an IgG1 isotype. Deposition of activated complement in the
      vessels of COPD lung as well as autoantibodies against endothelial cells were
      also observed. Ozone-exposed mice similarly exhibited increased antibody titers
      to carbonyl-modified protein, as well as activated antigen-presenting cells in
      lung tissue and splenocytes sensitized to activation by carbonyl-modified
      protein. CONCLUSIONS: Carbonyl-modified proteins, arising as a result of
      oxidative stress, promote antibody production, providing a link by which
      oxidative stress could drive an autoimmune response in COPD.

PMID- 21965014
TI  - Effect of five genetic variants associated with lung function on the risk of
      chronic obstructive lung disease, and their joint effects on lung function.
AB  - RATIONALE: Genomic loci are associated with FEV1 or the ratio of FEV1 to FVC in
      population samples, but their association with chronic obstructive pulmonary
      disease (COPD) has not yet been proven, nor have their combined effects on lung
      function and COPD been studied. OBJECTIVES: To test association with COPD of
      variants at five loci (TNS1, GSTCD, HTR4, AGER, and THSD4) and to evaluate joint
      effects on lung function and COPD of these single-nucleotide polymorphisms
      (SNPs), and variants at the previously reported locus near HHIP. METHODS: By
      sampling from 12 population-based studies (n = 31,422), we obtained genotype data
      on 3,284 COPD case subjects and 17,538 control subjects for sentinel SNPs in
      TNS1, GSTCD, HTR4, AGER, and THSD4. In 24,648 individuals (including 2,890 COPD
      case subjects and 13,862 control subjects), we additionally obtained genotypes
      for rs12504628 near HHIP. Each allele associated with lung function decline at
      these six SNPs contributed to a risk score. We studied the association of the
      risk score to lung function and COPD. MEASUREMENTS AND MAIN RESULTS: Association
      with COPD was significant for three loci (TNS1, GSTCD, and HTR4) and the
      previously reported HHIP locus, and suggestive and directionally consistent for
      AGER and TSHD4. Compared with the baseline group (7 risk alleles), carrying 10-12
      risk alleles was associated with a reduction in FEV1 (beta = -72.21 ml, P = 3.90
      * 10(-4)) and FEV1/FVC (beta = -1.53%, P = 6.35 * 10(-6)), and with COPD (odds
      ratio = 1.63, P = 1.46 * 10(-5)). CONCLUSIONS: Variants in TNS1, GSTCD, and HTR4
      are associated with COPD. Our highest risk score category was associated with a
      1.6-fold higher COPD risk than the population average score.

PMID- 21965017
TI  - Recommended reading from northwestern university fellows: peter h. S. Sporn,
      program director.

PMID- 21965016
TI  - Comparative effectiveness research in lung diseases and sleep disorders:
      recommendations from the National Heart, Lung, and Blood Institute workshop.
AB  - The Division of Lung Diseases of the National Heart, Lung, and Blood Institute
      (NHLBI) held a workshop to develop recommendations on topics, methodologies, and
      resources for comparative effectiveness research (CER) that will guide clinical
      decision making about available treatment options for lung diseases and sleep
      disorders. A multidisciplinary group of experts with experience in efficacy,
      effectiveness, implementation, and economic research identified (a) what types of
      studies the domain of CER in lung diseases and sleep disorders should include,
      (b) the criteria and process for setting priorities, and (c) current resources
      for and barriers to CER in lung diseases. Key recommendations were to (1)
      increase efforts to engage stakeholders in developing CER questions and study
      designs; (2) invest in further development of databases and other infrastructure,
      including efficient methods for data sharing; (3) make full use of a broad range
      of study designs; (4) increase the appropriate use of observational designs and
      the support of methodologic research; (5) ensure that committees that review CER
      grant applications include persons with appropriate perspective and expertise;
      and (6) further develop the workforce for CER by supporting training
      opportunities that focus on the methodologic and practical skills needed.

PMID- 21965018
TI  - Diffuse micronodules with spontaneous resolution.

PMID- 21965019
TI  - A trojan horse strategy to deliver amikacin to mycobacterial granulomas.

PMID- 21965020
TI  - Fine-needle aspiration cytology of ameloblastoma and malignant ameloblastoma: a
      study of 12 cases.
AB  - Ameloblastoma is an odontogenic tumor with aggressive biological behavior, high
      recurrence rate, and a complex microscopic appearance with many different
      histologic patterns. Primary ameloblastoma is also described in extragnathic
      locations. Because of its wide morphologic spectrum, which is mirrored also in
      cytologic smears, a thorough study of distinctive features is required to reach a
      reliable diagnosis. Twelve cases of ameloblastoma were examined both
      cytologically and histologically. The patients were seven women and five men 24
      85 years old, mean age being 64 years. Eleven cases were primary tumors of the
      mandible and maxilla, and one case was a lung tumor metastatic from the tibia.
      The epithelial element in the cytologic smears of the various cases was
      morphologically diverse. The basaloid pattern and minimal nuclear atypia were
      rather constant findings, and the most helpful features toward reaching a
      cytological diagnosis. However in most cases, careful consideration of the
      clinical, radiological, cytological, and occasionally immunocytochemical data was
      required to rule out other entities with similar cytological findings. In some
      cases, the final diagnosis was only possible by histologic examination. Due to
      their variable microscopic morphology, ameloblastomas are quite often
      misdiagnosed for other entities, both benign and malignant. Nevertheless, when
      one is aware of their distinctive features, an accurate diagnosis can be made by
      fine-needle aspiration cytology, in conjunction with clinical and radiological
      findings. Both the preoperative surgical planning and the postoperative follow-up
      of the patients benefit significantly from this method.

PMID- 21965022
TI  - Bile acids as modulators of enzyme activity and stability.
AB  - Bile acids deactivate certain enzymes, such as prolyl endopeptidases (PEPs),
      which are investigated as candidates for protease-based therapy for celiac sprue.
      Deactivation by bile acids presents a problem for therapeutic enzymes targetted
      to function in the upper intestine. However, enzyme deactivation by bile acids is
      not a general phenomenon. Trypsin and chymotrypsin are not deactivated by bile
      acids. In fact, these pancreatic enzymes are more efficient at cleaving large
      dietary substrates in the presence of bile acids. We targeted the origin of the
      apparently different effect of bile acids on prolyl endopeptidases and pancreatic
      enzymes by examining the effect of bile acids on the kinetics of cleavage of
      small substrates, and by determining the effect of bile acids on the
      thermodynamic stabilities of these enzymes. Physiological amounts (5 mM) of
      cholic acid decrease the thermodynamic stability of Flavobacterium
      meningosepticum PEP from 18.5 +/- 2 kcal/mol to 10.5 +/- 1 kcal/mol, while
      thermostability of trypsin and chymotrypsin is unchanged. Trypsin and
      chymotrypsin activation by bile and PEP deactivation can both be explained in
      terms of a common mechanism: bile acid-mediated protein destabilization. Bile
      acids, usually considered non-denaturing surfactants, in this case act as a
      destabilizing agent on PEP thus deactivating the enzyme. However, this level of
      global thermodynamic destabilization does not account for a more than 50%
      decrease in enzyme activity, suggesting that bile acids most likely modulate
      enzyme activity through specific local interactions.

PMID- 21965029
TI  - Use of novel and conventional biomarkers for management of patients with heart
      failure.
AB  - OPINION STATEMENT: Investigation of the complex biochemical pathways that
      underlie heart failure (HF) has led to the recognition of multiple molecular
      markers that may help to characterize patients with this disease. Although a
      myriad of novel biomarkers are being studied, most attention continues to be
      focused on the natriuretic peptides, brain natriuretic peptide (BNP) and N
      Terminal-proBNP (NT-proBNP). Numerous studies have established a role for these
      hormones in HF diagnosis and prognostication. More contentious has been their
      role in helping to guide HF management on a routine basis. This article aims to
      update the body of evidence surrounding conventional HF biomarkers and to
      highlight some emerging evidence on the use of novel markers. We believe that in
      select patients there may be a role for monitoring and cautious interpretation of
      HF biomarker levels to facilitate diagnosis, prognostication, and optimization of
      tailored therapy. However, there are not yet convincing data to suggest that
      routine hormone monitoring should be applied broadly and algorithmically to all
      HF patients. Moreover, to the extent that they are measured, HF biomarkers should
      serve only as a complement to-never as a substitute for-sound clinical judgment,
      watchful follow-up, and reliance on expert consultation when necessary.

PMID- 21965021
TI  - TNF-related apoptosis-inducing ligand (TRAIL) protects against diabetes and
      atherosclerosis in Apoe -/- mice.
AB  - AIMS/HYPOTHESIS: TNF-related apoptosis-inducing ligand (TRAIL) is implicated in
      the regulation of diabetes and is reduced in patients with cardiovascular
      disease. Although TRAIL receptors are widespread, and TRAIL can promote cell
      proliferation and apoptosis, it is not known how TRAIL might protect against
      diabetes and atherosclerosis. METHODS: We examined the development of
      atherosclerosis and diabetes in Apoe (-/-), Trail (also known as Tnfsf10)( -/- )
      Apoe ( -/- ) and Trail ( -/- ) mice that were fed a high-fat diet. Plasma
      cholesterol, triacylglycerol, glucose and insulin, as well as changes in various
      metabolic enzymes and regulators were assessed. Glucose and insulin tolerance
      tests were performed. Pancreatic islets were examined for insulin and beta cell
      dysfunction (apoptosis and macrophage infiltration). RESULTS: Compared with Apoe
      ( -/- ) mice, Trail ( -/- ) Apoe ( -/- ) and Trail ( -/- ) mice exhibited several
      features of diabetes, including increased weight, hyperglycaemia, reduced plasma
      insulin, impaired glucose tolerance, beta cell dysfunction, reduced islet
      insulin, macrophage infiltration and increased apoptosis. Trail ( -/- ) Apoe ( -/
      ) mice had increased plasma cholesterol, triacylglycerol, and VLDL- and LDL
      cholesterol, and increased expression of genes involved in cholesterol synthesis
      and lipogenesis. Trail ( -/- ) Apoe ( -/- ) mice also had increased
      atherosclerosis, with several features of plaque instability.
      CONCLUSIONS/INTERPRETATION: We show for the first time that TRAIL deficiency
      promotes numerous features of diabetes that are typical of human disease, and are
      associated with reduced insulin and pancreatic inflammation/apoptosis. TRAIL also
      regulates cholesterol and triacylglycerol homeostasis in Apoe ( -/- ) mice by
      increasing the expression of genes involved in (1) cholesterol synthesis and
      absorption, and (2) triacylglycerol production.

PMID- 21965030
TI  - The estimation of live weight based on linear traits in indigenous Tswana goats
      at various ages in Botswana.
AB  - The objective of this study was to determine the usefulness of some linear body
      measurements in predicting live weight in indigenous Tswana goats at various
      ages. Data for this study were obtained from 2,783 goats sampled from six
      agricultural regions of Botswana except for Tsabong and Ghanzi districts. Fifteen
      farmers keeping goats were randomly selected from each district and records taken
      on a random sample of 4-12 animals per farm depending on the 1999 Botswana
      Government average district flock size. Body measurements recorded were heart
      girth, height at withers, body length, shoulder width, and live weight.
      Information on age of each animal was estimated from dentition; flock size and
      sex of the animal were also recorded for each farm. Regression analysis using
      stepwise selection method in Statistical Analysis System was used to determine
      prediction equations for live weight with heart girth, height at withers, body
      length, and shoulder width as independent variables for male and female goats of
      different ages. In all models, heart girth contributed most in explaining
      variation in body weight as shown by high partial R(2) which ranged from 0.48 for
      female mature to 0.80 for mature male goats. Using mean square error, R(2), and
      Mallows' C(p), the best prediction equations were for female and male kids (R(2)
      = 0.83 and 0.82, respectively) and mature male goats (R(2) = 0.82). The poorest
      model was for mature female goats with R(2) = 0.57. Live body weight could be
      estimated with accuracy from linear body measurements in Tswana goats which are
      unique for each sex and age. More research is required to explore using these
      models to develop measuring tapes for use by resource poor farmers who keep
      indigenous Tswana goats.

PMID- 21965031
TI  - Semi-quantitative RT-PCR analysis of fat metabolism genes in mammary tissue of
      lactating and non-lactating water buffalo (Bubalus bubalis).
AB  - Understanding the mechanism of milk fat synthesis and secretion is important for
      dairy industry, as the nature of the cream fraction influences the manufacturing
      properties and organoleptic qualities of milk and dairy products. So, there is a
      need to understand the mechanism of milk fat synthesis and to elucidate the key
      genes regulating milk fat synthesis by studying the expression of genes involved
      in milk fat synthesis. Present manuscript reports the expression of genes
      involved in milk fat synthesis and metabolism in buffalo mammary tissue. The
      expression of lipogenic genes was studied in lactating and non-lactating mammary
      tissue of water buffalo by semi-quantitative reverse transcription PCR expression
      analysis. The genes studied were acetyl-CoA carboxylase (ACACA), stearoyl-CoA
      desaturase (SCD), 3 hydroxybutyrate dehydrogenase (BDH), LIPIN, lipoprotein
      lipase (LPL), peroxisome proliferator-activated receptor gamma (PPARG), and
      sterol regulatory element binding protein (SREBF). The expression of ACACA, BDH,
      LIPIN, PPARG, LPL, and SREBF was higher in lactating as compared to non-lactating
      buffalo whereas no difference was found in the expression of SCD between both the
      stages.

PMID- 21965032
TI  - DFT studies of COOH tip-functionalized zigzag and armchair single wall carbon
      nanotubes.
AB  - Structure and energy calculations of pristine and COOH-modified model single wall
      carbon nanotubes (SWCNTs) of different length were performed at B3LYP/6-31G*
      level of theory. From 1 to 9 COOH groups were added at the end of the nanotube.
      The differences in structure and energetics of partially and fully functionalized
      SWCNTs at one end of the nanotube are observed. Up to nine COOH groups could be
      added at one end of (9,0) zigzag SWCNT in case of full functionalization.
      However, for (5,5) armchair SWCNT, the full functionalization was impossible due
      to steric crowding and rim deformation. The dependence of substituent attachment
      energy on the number of substituents at the carbon nanotube rim was observed.

PMID- 21965033
TI  - Computational investigation of a new ion-pair receptor for calix[4]pyrrole.
AB  - Theoretical studies of a new ion-pair receptor, meso-octamethylcalix[4]pyrrole
      (OMCP), and its interactions with the halide anions F(-), Cl(-), and Br(-) and
      the cesium halides CsF, CsCl, and CsBr have been performed. Geometries, binding
      energies, and binding enthalpies were evaluated with the restricted hybrid Becke
      three-parameter exchange functional (B3LYP) method using the 6-31+G(d) basis set
      and relativistic effective core potentials. The optimized geometric structures
      were used to perform natural bond orbital (NBO) analysis. The two typical types
      of hydrogen bonds, N-H...X(-) and C-H...X(-), were investigated. The results
      indicate that hydrogen bonding interactions are dominant, and that the halide
      anions (F(-), Cl(-), and Br(-)) offer lone pair electrons to the sigma*(N-H) or
      sigma*(C-H) antibonding orbitals of OMCP. In addition, electrostatic interactions
      between the lone pair electrons of the halide anion and the LP* orbitals of Cs(+)
      as well as cation-pi interactions between the metal ion and pi-orbitals of the
      pyrrole rings have important roles to play in the Cs(+)*OMCP*X(-) complexes. The
      current study further demonstrates that this easy-to-make OMCP host compound
      functions as not only an anion receptor but also an ion-pair receptor.

PMID- 21965034
TI  - Why is the crystal shape of TATB is so similar to its molecular shape?
      Understanding by only its root molecule.
AB  - We present an understanding of the quasi-regular or regular hexagonal enlargement
      of 1,3,5-triamino-2,4,6 (TATB) from its root molecule to its bulk crystal, by
      only its root molecule. That is, the mechanism of regular hexagonal TATB
      molecules stacking to a quasi-regular or regular hexagonal TATB crystal was
      discussed using a combined method of a density functional theory BLYP and
      Dreiding forcefield, and a series of static scanning calculations. As a result,
      we found that there are two styles of forming the most energetically favored TATB
      dimers: a hydrogen bonding along the molecular plane and an offset pi-stacking
      vertical to the plane, just leading to the outspread and the thickening of the
      regular hexagon during the crystal growth, respectively. At the same time, it was
      found that the rotation of one TATB layer in any parallel stacked double-layer
      should overcome a very high energy barrier. It suggests that the TATB molecules
      or layers are arranged on the crystal face always along the special orientation
      of a regular hexagon and other orientations are strongly thermodynamically
      forbidden, resulting in a hexagonal crystal bulk.

PMID- 21965035
TI  - [Urinary peptides and calcium oxalate nephrolithiasis, a combined approach: MALDI
      TOF mass spectrometry and MicroBCA Protein Assay].
AB  - BACKGROUND: Urinary lithiasis is one of the most common benign urological
      diseases. There is growing evidence that a delicate equilibrium regulated by the
      function of proteins, soluble peptides, membrane proteins and intracellular
      mechanisms actually exists. We have studied the urinary protein composition of
      patients affected by calcium oxalate nephrolithiasis in order to discover a
      biomarker or any predisposing factors. METHODS: The urinary protein composition
      of 17 patients (11 males, 6 females; mean age 45yrs +/- 14SD), affected by
      calcium oxalate nephrolithiasis, was assessed in comparison with 17 healthy
      subjects. A qualitative assay was performed using MALDI-TOF mass spectrometry in
      a spectrum between 1 and 5kDa (medium size peptides), and a numerical
      (quantitative) assay using specific filters and MicroBCA Protein Assay. RESULTS:
      No differences were detected in the mass spectrums between patients and control
      subjects: all peaks overlapped perfectly. The results of the numerical assay
      suggest that concentrations of protein species <5kDa in control samples were
      actually higher than those which were found in patients. The differences are
      statistically significant. CONCLUSIONS: The study detected neither a biomarker
      nor any predisposing factors in "stone former" patients. The assessment of the
      results obtained, in terms of quantitative differences, indicate the need for
      further research.

PMID- 21965036
TI  - Liver haemostasis using microbubble-enhanced ultrasound at a low acoustic
      intensity.
AB  - OBJECTIVES: To explore the haemostatic effects of microbubble-enhanced ultrasound
      (MEUS) at a very low acoustic intensity on the bleeding liver of rabbits.
      METHODS: Liver incisions made on 20 rabbits were treated with a pulsed
      therapeutic ultrasound transducer. The transducer was operated at 831 KHz with an
      acoustic intensity of 0.4 W/cm(2). The treatment was coordinated with intravenous
      injection of microbubbles. Ultrasound only and sham treatment served as the
      controls. Visual bleeding score and 10-min bleeding volume were evaluated for
      haemostatic efficacy. Contrast-enhanced ultrasound (CEUS) was performed to assess
      the liver perfusion. Nine treated livers were harvested for acute histological
      examination. RESULTS: Regarding the bleeding incisions made on rabbit livers, the
      haemorrhage stopped immediately after 2 min of MEUS treatment but bleeding
      continued in the controls treated by ultrasound or microbubble injection alone.
      The bleeding scores and the 10-min haemorrhagic volumes dropped significantly in
      the MEUS group compared with those of the controls (p < 0.01). The mechanism of
      MEUS haemostasis appears to involve the extensive swelling of hepatocytes and the
      haemorrhage of the portal area, which formed a joint compression on the regional
      liver circulation. CONCLUSIONS: Low acoustic intensity MEUS might provide a novel
      method for liver haemostasis. KEY POINTS: * This animal experiment demonstrates a
      novel method of controlling hepatic haemorrhage * The treatment uses therapeutic
      ultrasound during enhancement with intravenous microbubbles * This combined
      therapy was more effective than ultrasound or intravenous microbubbles alone *
      More work is required with larger animals before potential human trials.

PMID- 21965037
TI  - Diagnostic performance of 64-section CT using CT gastrography in preoperative T
      staging of gastric cancer according to 7th edition of AJCC cancer staging manual.
AB  - OBJECTIVES: To evaluate the accuracy of 64-section multidetector CT with CT
      gastrography for determining the depth of mural invasion in patients with gastric
      cancer according to the 7th edition of the AJCC cancer staging manual. METHODS: A
      total of 127 patients with gastric cancer and who had undergone both esophago
      gastro-duodenoscopy and 64-section CT were included in this study. Two
      radiologists independently reviewed the preoperative CT images with respect to
      the detectability and T-staging of the gastric cancers. The sensitivity,
      specificity, accuracy and overall accuracy of each reviewer for the T staging of
      gastric cancer were calculated. RESULTS: Overall, gastric cancer was detected in
      123 (96.9%) of the 127 cancers on the CT images. Reviewer 1 correctly staged 98
      gastric cancers, and reviewer 2 correctly classified 105 gastric cancers. The
      overall diagnostic accuracy of the T staging was 77.2% (98/127) for reviewer 1
      and 82.7% (105/127) for reviewer 2. CONCLUSION: 64-section CT using CT
      gastrography showed a reasonable diagnostic performance for determining the T
      staging in patients with gastric cancer according to the 7th edition of the AJCC
      cancer staging manual. KEY POINTS: 64-section CT is useful for determining the T
      staging of gastric cancer Virtual gastroscopy is helpful for detecting early
      gastric cancer New CT criteria may be applicable to the T staging The normal
      gastric wall frequently shows a multilayered pattern.

PMID- 21965038
TI  - Radiological diagnosis of incomplete partition type I versus type II:
      significance for cochlear implantation.
AB  - OBJECTIVES: To investigate an extended cohort of patients with incomplete
      partition (IP) and examine the adequacy of the existing classifications based on
      radiological criteria and on their implications for cochlear implantation.
      METHODS: Patients with IP admitted to a tertiary referral centre during the
      period 2000-2010 were retrospectively examined. The subjects were initially
      classified into IP-I, IP-II and atypical cases. For cochlear implant recipients
      relevant aspects were analysed. RESULTS: Eighty-three ears (49 patients) with IP
      were found, 19 with IP-I, 54 with IP-II and 10 atypical. Thirty-three patients
      received a cochlear implant (11 with IP-I, 19 with IP-II and three atypical)
      achieving heterogeneous though mostly promising results. Cerebrospinal fluid
      gushing was the commonest surgical complication, particularly in cases of IP-I.
      In general, patients with IP-II performed better than those with IP-I.
      CONCLUSIONS: Cochlear implantation promises adequate hearing rehabilitation for
      most patients with IP. As we move from IP-I to IP-II better results and lower
      risk for gushing shall be expected. Based on radiological findings we suggest a
      modified classification into IP-I, atypical IP-I (with large vestibular aqueduct
      (LVA) and better partition), IP-II (Mondini deformity) and atypical IP-IIa
      (without LVA) and b (without LVA but with semicircular canal dysplasia). KEY
      POINTS: * Radiological (CT and MR) features are of crucial importance for
      cochlear implantation * Imaging can identify two types of incomplete cochlear
      partition and atypical cases * Detailed pre-operative radiological assessment can
      help predict complications and outcome * A more comprehensive radiological
      classification of these anomalies is proposed.

PMID- 21965039
TI  - Actinomyces naturae sp. nov., the first Actinomyces sp. isolated from a non-human
      or animal source.
AB  - Three facultatively anaerobic, Gram-positive staining, rod-shaped, non-spore
      forming, flagellated bacterial strains, BL-75, BL-79(T) and BL-104, were isolated
      from chlorinated solvent-contaminated groundwater. Phylogenetic analysis based on
      16S rRNA gene sequence comparisons showed them to represent a distinct lineage
      within the genus Actinomyces with sequence identities in the range of <88-95.4%
      with previously described Actinomyces species. The strains were oxidase and
      catalase negative. Nitrate was not reduced. Esculin was hydrolyzed. Growth
      occurred in the temperature range of 20-43 degrees C (optimum 30-37 degrees C)
      and pH range 4.5-9.0 (optimum pH 6.5). Substrates supporting growth included
      various mono-, di-, and tri-saccharides. The end products of glucose fermentation
      were acetate, lactate, succinate and formate. Fermentative growth was observed in
      the presence of near saturation concentrations of perchloroethene (PCE) and
      toluene and in the presence of 1,2-dichloroethane and 1,1,2-trichloroethane at
      concentrations up to at least 24.4 mM and 11.2 mM, respectively. The dominant
      cellular fatty acids when grown in peptone/yeast extract/glucose (PYG) medium
      were C(18:1) omega9c, C(16:0), and C(14:0). The peptidoglycan was found to
      contain the amino acids alanine, glutamic acid, lysine, and ornithine at
      approximate molar ratios of 1.7 Ala: 2.3 Glu: 1.3 Lys: 1.0 Orn. The cell wall
      sugars were found to include rhamnose and mannose. The polar lipids were found to
      include diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), phospholipid
      (PL), phosphoglycolipids (PGL), and glycolipids (GL). The main respiratory
      quinone of strain BL-79(T) was MK-9(H(4)), with minor components MK-10(H(4)) and
      MK-8(H(4)). The DNA mol% G+C content of the type strain is 69.8%. On the basis of
      phylogenetic and phenotypic characteristics, these strains could be
      differentiated from previously described species of the genus Actinomyces.
      Strains BL-75, BL-79(T) and BL-104 are designated as a novel species, for which
      the name Actinomyces naturae sp. nov. is proposed. This is the first Actinomyces
      species isolated from an environmental rather than human or animal sources. The
      type strain of Actinomyces naturae is BL-79(T) (= CCUG 56698(T) = NRRL B
      24670(T)).

PMID- 21965040
TI  - The role of DNA base excision repair in filamentation in Escherichia coli K-12
      adhered to epithelial HEp-2 cells.
AB  - Base excision repair (BER) is dedicated to the repair of oxidative DNA damage
      caused by reactive oxygen species generated by chemical and physical agents or by
      metabolism which can react with DNA and cause a variety of mutations. Epithelial
      cells are typically the first type of host cell to come into contact with
      potential microbial invaders. In this work, we have evaluated whether the
      adherence to human epithelial cells causes DNA damage and associated
      filamentation. Experiments concerning adherence to HEp-2 cells were carried out
      with mutants deficient in BER that were derived from Escherichia coli K-12. Since
      the removal of mannose during bacterial interaction with HEp-2 cells allows
      adhesion through mannose-sensitive adhesins, the experiments were also performed
      in the presence and the absence of mannose. Our results showed enhanced
      filamentation for the single xth (BW9091) and triple xth nfo nth (BW535) mutants
      in adherence assays with HEp-2 cells performed without D: -mannose. The increased
      filamentation growth was inhibited by complementation of BER mutants with a wild
      type xth gene. Moreover, we measured SOS induction of bacteria adhered to HEp-2
      cells in the presence and absence of D: -mannose through of SOS-chromotest assay
      and we observed a higher beta-galactosidase expression in the absence of mannose.
      In this context, data showed evidence that bacterial attachment to HEp-2
      epithelial surfaces can generate DNA lesions and SOS induction.

PMID- 21965042
TI  - Left sided omental torsion with left inguinal hernia: a rare entity.

PMID- 21965041
TI  - Selection-driven divergence after gene duplication in Arabidopsis thaliana.
AB  - Gene duplications are one of the most important mechanisms for the origin of
      evolutionary novelties. Even though various models of the fate of duplicated
      genes have been established, current knowledge about the role of divergent
      selection after gene duplication is rather limited. In this study, we analyzed
      sequence divergence in response to neo- and subfunctionalization of segmentally
      duplicated genes in the genome of Arabidopsis thaliana. We compared the genomes
      of A. thaliana and the poplar Populus trichocarpa to identify orthologous pairs
      of genes and their corresponding inparalogs. Maximum-likelihood analyses of the
      nonsynonymous and synonymous substitution rate ratio [Formula: see text] of pairs
      of A. thaliana inparalogs were used to detect differences in the evolutionary
      rates of protein coding sequences. We analyzed 1,924 A. thaliana paralogous pairs
      and our results indicate that around 6.9% show divergent omega values between the
      lineages for a fraction of sites. We observe an enrichment of regulatory
      sequences, a reduced level of co-expression and an increased number of
      substitutions that can be attributed to positive selection based on an McDonald
      Kreitman type of analysis. Taken together, these results show that selection
      after duplication contributes substantially to gene novelties and hence
      functional divergence in plants.

PMID- 21965043
TI  - mRNA expression of cytokines and its impact on outcomes after infection with
      lethal and nonlethal Plasmodium vinckei parasites.
AB  - Cytokines play an important role in the defense against malaria and some have
      long been documented to influence the course of malaria infection in rodents and
      humans. The present study was conducted to determine the mRNA expression pattern
      of a few prominent cytokines at different time points during the course of
      infection with a nonlethal and lethal Plasmodium vinckei rodent malaria parasite,
      using highly sensitive real-time PCR. Analysis of mRNA expression of cytokines in
      spleen from infected mice revealed that the principal difference was an early
      depletion in pro-inflammatory cytokine's mRNA expression in mice infected with
      lethal P. vinckei (PvAS) parasites. In addition, an increase in anti-inflammatory
      cytokines particularly IL-10 mRNA expression levels was found in the same group
      of mice. In contrast, the significant rise in pro-inflammatory cytokine's mRNA
      expression levels was recorded at day 1 onwards after infection with nonlethal P.
      vinckei (PvAR). The maximum fold change was recorded for IFN-gamma and IL-10,
      when compared to baseline value. TGF-beta did not seem to play any major role in
      P. vinckei infection.

PMID- 21965044
TI  - Transmitted deletions of medial 5p and learning difficulties; does the cadherin
      cluster only become penetrant when flanking genes are deleted?
AB  - The central portion of the short arm of chromosome 5 is unusual in that large,
      cytogenetically visible interstitial deletions segregate in families with and
      without phenotypic consequences. Here we present a family in which a transmitted
      interstitial deletion of 5p13.3 to 5p14.3 co-segregated with learning and/or
      behavioral difficulties in six family members. Facial dysmorphism was not
      striking but a father and daughter both had lacrimal fistulae. The deletion was
      12.23 Mb in size (chr5:20,352,535-32,825,775) and contained fifteen known protein
      coding genes. Five of these (GOLPH3; MTMR12; ZFR; SUB1; and NPR3) and an ultra
      conserved microRNA (hsa-miR-579) were present in an 883 kb candidate gene region
      in 5p13.3 that was deleted in the present family but not in previously reported
      overlapping benign deletions. Members of the cadherin precursor gene cluster,
      with brain specific expression, were deleted in both affected and benign deletion
      families. The candidate genes in 5p13.3 may be sufficient to account for the
      consistent presence or absence of phenotype in medial 5p deletions. However, we
      consider the possibility of position effects in which CDH6, and/or other cadherin
      genes, become penetrant when adjacent genes, or modifiers of gene expression, are
      also deleted. This could account for the absence of intellectual disability in
      benign deletions of the cadherin cluster, the cognitive phenotype in medial 5p
      deletion syndrome and the greater severity of intellectual disability in patients
      with cri-du-chat syndrome and deletions of 5p15 that extend into the region
      deleted in the present family.

PMID- 21965045
TI  - Morphometric features and glycoconjugate pattern of rabbit intestine are affected
      by particle size of pelleted diets.
AB  - Feed particle size effects on morphology and glycoconjugate pattern was
      investigated in the rabbit intestine. Rabbits fed with fine particles (2 mm)
      displayed more irregularly shaped, higher duodenal villi and deeper crypts in
      distal colon as well as higher number of goblet cells than coarse (8 mm) fed
      ones. Brush border expressed: (i) in duodenum, neutral/sulfated glycoconjugates
      and glycans binding MAL II, SNA, Con A than KOH-sialidase-PNA and DBA reactivity
      in fine and coarse fed rabbits, respectively, (ii) in cecum, mainly sulfoglycans
      in coarse fed rabbits, MAL II and PNA staining in all samples, and (iii) in
      distal colon few sulfoglycans and MAL II reactivity. Enterocytes bound MAL II in
      duodenum, Con A in cecum, DBA, and Con A in distal colon of all rabbits, SNA in
      distal colon of coarse fed ones. Brunner's glands displayed high presence of
      acidic/sulfated mucins in fine fed rabbits, neutral glycoconjugates and
      reactivity with MAL II, SNA, PNA, KOH-sialidase-PNA, and Con A in all rabbits.
      Goblet cells exhibited: (i) in duodenum neutral and sulfomucins as well as MAL II
      and KOH-sialidase-PNA staining, than SNA and DBA in fine and coarse fed rabbits,
      respectively, (ii) in cecum sulfated glycans, MAL II, SNA, KOH-sialidase-PNA, DBA
      reactivity, and (iii) in distal colon acidic/sulfomucins, MAL II and SNA
      staining, and DBA reactivity in fine fed specimens. Crypt cells exhibited neutral
      and PNA reactive glycoconjugates in the cecum. In the distal colon also
      acidic/sulfated glycans, and MAL II, KOH-sialidase-PNA, DBA; SNA staining showed
      weaker reactivity in fine fed rabbits, which bound Con A.

PMID- 21965046
TI  - Clinical progression of incidental tomographic findings in paranasal sinuses of
      asymptomatic individuals: cohort study.
AB  - OBJECTIVE: To determine whether the presence of opacification in the paranasal
      sinuses of children and adolescents without rhinosinusitis implies an increased
      risk of later development of upper respiratory tract symptoms. METHODS: This was
      a prospective study of a cohort of patients aged 0 to 18 years who underwent
      computerized tomography (CT) scans for indications unrelated to rhinosinusitis.
      Sinus opacification was evaluated using an opacification/development ratio score.
      The patients' clinical progression was followed up using a questionnaire for 1
      month after the scans. RESULTS: Fifty-six percent (56%) of the 106 patients
      enrolled in the study had opacity, the majority due to mucosal thickening.
      Intense opacification was defined as "suspected" (score >= 15) and patients in
      this subset had a greater risk of developing symptoms during follow-up (odds
      ratio = 2.74; 95%CI 1.10-6.83) compared to those with no findings or discrete
      findings. CONCLUSIONS: Intense incidental sinus opacity on CT indicates a risk of
      future development of a clinical respiratory condition.

PMID- 21965047
TI  - Therapeutic potential of the proteasome inhibitor Bortezomib on titanium particle
      induced inflammation in a murine model.
AB  - Wear particle-induced aseptic loosening has been recognized as a harmful
      inflammatory process that jeopardizes the longevity of total joint replacement.
      The proteasome controls the activation of NF-kappaB and subsequent inflammatory
      mediators, such as TNF-alpha and IL-1beta; thus, we investigated whether
      proteasome inhibition can ameliorate wear particle-induced inflammation in a
      murine model. A total of 48 BALB/C mice were divided into four groups. Titanium
      (Ti) particles were injected into the established air pouches of all mice (except
      negative controls) to provoke inflammation, and then 0.1 or 0.5 mg/kg of
      Bortezomib (Bzb, a proteasome inhibitor) was administered to ameliorate the
      inflammation response, while air pouches without Bzb administration were used as
      loading controls. The air pouches were harvested 2 or 7 days after Bzb injection
      for molecular and histological analyses. Inflammation responses in the air pouch
      tissues of Bzb treatment groups are lower than those in the Ti-stimulated group,
      and this occurs in a dose-dependent manner. Bzb can significantly attenuate the
      severity of Ti-induced inflammation in air pouches.

PMID- 21965048
TI  - Force and pressure distribution using Macintosh and GlideScope laryngoscopes in
      normal and difficult airways: a manikin study.
AB  - BACKGROUND: The forces applied to the soft tissues of the upper airway may have a
      deleterious effect. This study was designed to evaluate the performance of the
      GlideScope compared with the Macintosh laryngoscope. METHODS: Twenty
      anaesthetists and 20 trainees attempted tracheal intubation of a Laerdal SimMan
      manikin. Forces and pressure distribution applied by both laryngoscope blades
      onto the soft upper airway tissues were measured using film pressure transducers.
      The minimal force needed to achieve a successful intubation, in the same
      simulated scenario, was measured; additionally, we considered the visualization
      score achieved by using the Cormack-Lehane grades. RESULTS: All participants
      applied, on average, lower force with the GlideScope than with the Macintosh in
      each simulated scenario. Forces [mean (sd)] applied in the normal airway scenario
      [anaesthetists: Macintosh 39 (22) N and GlideScope 27 (15) N; trainees: Macintosh
      45 (24) N and GlideScope 21 (15) N] were lower than forces applied in the
      difficult airway scenario [anaesthetists: Macintosh 95 (22) N and GlideScope 66
      (20) N; trainees: Macintosh 100 (38) N and GlideScope 48 (16) N]. All the
      intubations using the GlideScope were successful, regardless of the scenario and
      previous intubation experience. The average pressure on the blades was 0.13 MPa
      for the Macintosh and 0.07 MPa for the GlideScope, showing a higher uniformity
      for the latter. CONCLUSIONS: The GlideScope allowed the participants to obtain a
      successful intubation applying a lower force. A flatter and more uniform pressure
      distribution, a higher successful rate, and a better glottic view were observed
      with the GlideScope.

PMID- 21965049
TI  - Role of coerulean noradrenergic neurones in general anaesthesia in rats.
AB  - BACKGROUND: Central noradrenergic neurones have a role in alertness, analgesia,
      and thermoregulation; these neurones are also involved in the mechanism of
      anaesthesia. Locus coeruleus neurones innervate various central nervous regions
      including the cerebral cortex and hippocampus, and are responsible for
      wakefulness and analgesia. We hypothesized that these neurones are also involved
      in both activation of the gamma-aminobutyric acid type A (GABA(A)) receptor and
      inhibition of N-methyl-d-aspartate (NMDA) receptor-mediated anaesthesia. METHODS:
      Forty-seven male rats were used to compare duration of anaesthesia before and 10
      days after noradrenergic neurone depletion after intraperitoneal (i.p.)
      administration of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4; 0, 5, and
      50 mg kg(-1)). The animals received i.p. thiopental (GABA anaesthetic, 45 mg kg(
      1)) or ketamine (NMDA anaesthetic, 100 mg kg(-1)). We also tested the effects of
      coerulean noradrenergic neurone depletion on i.p. ketamine analgesia (15 mg kg(
      1)) using the hot-plate test in a further 21 male rats. At the end of each
      experiment, norepinephrine contents in the cerebral cortex and hippocampus were
      measured. RESULTS: I.P. DSP-4 5 and 50 mg kg(-1) significantly decreased ketamine
      anaesthesia duration by 12.7% and 22.4%, increased thiopental anaesthesia
      duration by 10.8% and 24.5%, and reduced ketamine-increased hot-plate latency by
      55.2% and 68.1%, respectively. In addition, i.p. DSP-4 5 and 50 mg kg(-1)
      significantly reduced norepinephrine contents in coerulean brain regions by ~20%
      and ~75%, respectively. There were significant correlations between
      norepinephrine contents in coerulean brain regions and anaesthesia durations and
      ketamine analgesia. CONCLUSIONS: The present data indicate that coerulean
      noradrenergic neurones may be responsible for both GABA- and NMDA-mediated
      anaesthetic actions.

PMID- 21965050
TI  - Nitrous oxide (N(2)O) reduces postoperative opioid-induced hyperalgesia after
      remifentanil-propofol anaesthesia in humans.
AB  - BACKGROUND: The aim of this study was to test if intraoperative administration of
      N(2)O during propofol-remifentanil anaesthesia prevented the onset of
      postoperative opioid-induced hyperalgesia (OIH). METHODS: Fifty adult ASA I-II
      patients undergoing elective open septorhinoplasty under general anaesthesia were
      studied. Anaesthesia was with propofol, adjusted to bispectral index (40-50), and
      remifentanil (0.30 MUg kg(-1) min(-1)). Patients were assigned to one of the two
      groups: with N(2)O (70%) and without N(2)O (100% oxygen). Mechanical pain
      thresholds were measured before surgery and 2 and 12-18 h after surgery. Pain
      measurements were performed on the arm using hand-held von Frey filaments. A non
      parametric analysis of variance was used in the von Frey data analysis. P<0.05
      was considered statistically significant. RESULTS: Baseline pain thresholds to
      mechanical stimuli were similar in both groups, with mean values of 69 [95%
      confidence interval (CI): 50.2, 95.1] g in the group without N(2)O and 71 (95%
      CI: 45.7, 112.1) g in the group with N(2)O. Postoperative pain scores and
      cumulative morphine consumption were similar between the groups. The analysis
      revealed a decrease in the threshold value in both groups. However, post hoc
      comparisons showed that at 12-18 h after surgery, the decrease in mechanical
      threshold was greater in the group without N(2)O than the group with N(2)O (post
      hoc analysis with Bonferroni's correction, P<0.05). CONCLUSIONS: Intraoperative
      70% N(2)O administration significantly reduced postoperative OIH in patients
      receiving propofol-remifentanil anaesthesia.

PMID- 21965051
TI  - Effects of airway occlusion on breathing muscle electromyogram signals, during
      isoflurane anaesthesia, with and without the effects of fentanyl and hypercapnia.
AB  - BACKGROUND: Expiratory muscle action is prominent during anaesthesia and can
      impair lung function. This activity is exaggerated by the use of opioids. Airway
      pressure during occlusion of expiration would be a valuable measure in the study
      of expiratory muscle activation. However, this would only be valid if the imposed
      occlusion did not itself alter muscle activation. This possibility can be checked
      by directly assessing muscle activity by electromyography; varying arterial
      carbon dioxide tensions and opioid action should be considered. METHODS: We
      studied seven spontaneously breathing patients, anaesthetized with nitrous oxide
      and isoflurane, in four conditions: during an infusion of fentanyl and after
      naloxone, breathing normally and with breathing stimulated with CO(2). We
      compared diaphragm and external oblique abdominal electromyogram (EMG) signals
      during normal and occluded breaths. We also measured chest wall volume and
      compared airway occlusion pressure, during inspiration and expiration, with the
      EMG results. RESULTS: Inspiratory occlusion increased the duration of inspiration
      during hypercapnia by 20%, but not the rate of electrical activation of the
      diaphragm, indicating that occlusion does not cause a reflex increase in
      diaphragm contraction. In contrast, expiratory occlusion did not affect either
      the duration of expiration or the electrical activity of the external oblique
      muscles. CONCLUSIONS: In these conditions, except for a change in inspiratory
      duration, respiratory muscle activity is unaffected by airway occlusion. Airway
      occlusion will permit valid measures of muscle activity in inspiration and
      expiration and provide simple measurements of respiratory muscle function during
      anaesthesia.

PMID- 21965052
TI  - Expression of Ki-67 as proliferation biomarker in imprint smears of endometrial
      carcinoma.
AB  - The aims of this study were to determine the expression of Ki-67 in type I and
      type II endometrial adenocarcinomas as well as normal endometrium in imprint
      smears and to correlate the results with clinicopathologic parameters of primary
      untreated endometrial cancer patients. During a 29-month period, 255 patients
      were evaluated with entometrial imprint cytology. Endometrial samples freshly
      resected from women who underwent total abdominal hysterectomy were studied. One
      hundred twenty-six patients had endometrial carcinoma and 129 cases were
      diagnosed as normal endometrium. The expression of Ki-67 was assessed by
      immunocytochemistry. Positive staining was correlated with increased stage, grade
      and lymph node metastases. High expression was more frequent in type II than type
      I endometrial adenocarcinoma and high-grade endometrial carcinoma had higher
      proportions of Ki-67 positive immunostaining compared with low-grade carcinoma.
      Proliferative endometrium showed high Ki-67 expression level, even higher than
      those of grade 1 and type I. On the other hand, secretory endometrium Ki-67
      positive cells were markedly diminished and even disappeared. Completely negative
      staining was found to be related to atrophic endometrium. Immunocytochemical
      findings from Ki-67 stain, in addition to cytomorphologic features, appeared to
      be useful for the diagnosis of endometrial carcinoma in endometrial cytology with
      imprint smears. High Ki-67 expression correlates with morphologic features of
      aggressiveness and the expression pattern of Ki-67 correspond to the expected
      cyclic/atrophic pattern in normal endometrium.

PMID- 21965053
TI  - Assessment of left ventricular twist mechanics in Tako-tsubo cardiomyopathy by
      two-dimensional speckle-tracking echocardiography.
AB  - AIMS: To assess left ventricular (LV) twist mechanics in patients with Tako-tsubo
      cardiomyopathy (TTC). METHODS AND RESULTS: Two-dimensional strain and LV twist by
      speckle-tracking echocardiography was performed in 17 consecutive patients with
      typical TTC according to the Mayo clinic criteria [78 +/- 8 years, 88% women, and
      mean left ventricular ejection fraction (LVEF) 45 +/- 10%], at the acute phase
      (within 24 h after admission) and after recovery (1 month later). Seventeen
      control (C) patients matched for age and sex (mean LVEF 70 +/- 7%), and 17
      patients with acute anterior myocardial infarction (MI) treated by successful
      primary angioplasty 24 h before, matched for LVEF, age, and sex, were compared
      with TTC patients. LV twist was assessed using the parasternal basal and apical
      short-axis planes, and defined as the net difference in degrees of apical (Ar)
      and basal rotation (Br). Peak systolic and early diastolic, apical (As and Ad)
      and basal (Bs and Bd) rotation rate, and LV twisting rate (TR) and untwisting
      rate (UR) (in  degrees /s) were derived from rotational and twist curves. The
      time sequences were normalized to the percentage of systolic duration. At the
      acute phase, Ar, As, Ad, Bs, LV twist (10 +/- 9 degrees  vs. 23 +/- 6 degrees ),
      LV TR, and LV UR were significantly impaired in patients with TTC when compared
      with controls (all, P < 0.05). Patients with MI displayed intermediate values (P
      = NS vs. TTC, and P < 0.05 vs. C). However, in the subgroup of patients with
      electrocardiogram ST-segment elevation at presentation (n = 12 TTC and 17 MI),
      several LV twist mechanics parameters were significantly reduced in TTC patients
      when compared with MI patients, LV twist, and LV TR being the most significant
      factors (all, P<= 0.01). Abnormal reversed Ar (clockwise when seen from the apex)
      was seen in three patients (18%) with TTC vs. none in the other groups. A
      significant correlation between LV twist and LVEF, LV volumes, wall motion score
      index, and plasma NT-pro BNP was observed in the TTC group (all, P < 0.05). At
      follow-up, LV twist mechanics improved significantly in TTC patients (all, P <
      0.05 vs. acute phase), who had final values similar to C (all, P = NS), whereas
      the magnitude of improvement was lower in MI patients (P <= 0.05 vs. TTC).
      CONCLUSION: LV twist mechanics is significantly impaired in patients with TTC
      mainly due to a severe reduction in apical function and is entirely reversible.
      Furthermore, in the subgroup of patients with ST-segment elevation, the early
      post-admission evaluation of LV twist mechanics is more severely impaired in TTC
      when compared with MI.

PMID- 21965054
TI  - Robustness of a new three-dimensional echocardiographic algorithm for left
      ventricular volume and ejection fraction quantification: experts vs. novices.
AB  - AIMS: We evaluated the ability of a new simplified algorithm for three
      dimensional echocardiography (3DE) left ventricular (LV) measurements with
      minimal operator interaction to be reproducible and robust, independently of the
      experience. METHODS AND RESULTS: A total of 163 subjects were investigated using
      two-dimensional echocardiography (2DE) and 3DE. The 3D data sets were blindly
      analysed offline by novice investigators and experts. A subgroup of 30 patients
      was assessed using cardiac magnetic resonance imaging (CMRI) to compare end
      diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF)
      obtained by 2DE, 3DE, and CMRI. Intra-observer and inter-observer variabilities
      of 2DE and 3DE measurements were evaluated according to level of experience. Mean
      time analysis of 3DE data was 23.2 +/- 6.3s for the novice and 26.1 +/- 4.1 s for
      the expert (P = ns). Correlations (r) and mean error measurements (MEM) between
      3DE analysis by experts and novices were 0.91 and -3.5 mL for EDV, 0.97 and 4.3
      mL for ESV, and 0.91 and -2.6% for EF, respectively. Correlations between 3DE and
      CMRI were good with low variability and greater agreement when compared with
      those between 2DE and CMRI. For the novice, MEM was -21.3 mL for EDV, -15.0 mL
      for ESV, and 2.3% for EF. MEM and 95% confidence intervals were wider for 2DE vs.
      CMRI than for 3DE vs. CMRI in relation to both expert and novice. CONCLUSION:
      This new semi-automated algorithm of LV endocardial border detection based on 3DE
      data appears suitable for clinical use by either expert or novice investigators
      with greater reproducibility and time of analysis than 2DE.

PMID- 21965055
TI  - Pulmonary Doppler signals: a potentially new diagnostic tool.
AB  - AIMS: To overcome the limitations due to ultrasound attenuation by the air in the
      lungs, in order to study the pulmonary system using an advanced signal processing
      technology. METHODS AND RESULTS: Pulsed spectral Doppler signals were obtained
      over the chest wall using a signal processing and algorithm package
      (transthoracic parametric Doppler, TPD, EchoSense Ltd, Haifa, Israel) in
      conjunction with a non-imaging Doppler device (Viasys Healthcare, Madison, WI,
      USA) coupled with an electrocardiogram. The signals picked up by a transducer
      positioned at various locations over the chest wall, were treated for noise,
      analysed parametrically and displayed in terms of both velocity and power
      originating from moving ultrasound reflectors. Clear reproducible lung Doppler
      signals (LDS) were recorded. Up to five bidirectional triangular waves with peak
      velocities of 20-40 cm/s, that survived the 40 dB/cm attenuation of the lung,
      were recorded during each cardiac cycle. The first signal coincides with early
      ventricular systole, the second with late systole, the third and fourth with
      diastole, and the last with atrial contraction. CONCLUSION: LDS originate from
      different elements and phases of cardiac activity that generate mechanical waves
      which propagate throughout the lung and are thus expressed in pulsatile changes
      in ultrasound reflections. While such signals could originate either from
      pulsatile blood flow or reflections from movement of the blood vessel--alveolar
      air interface, the experimental evidence points towards the tissue--air interface
      movements due to vessel expansion as the origin. The LDS can potentially be an
      important tool for diagnosing and characterizing cardio-pulmonary physiological
      states and diseases.

PMID- 21965056
TI  - The relationship between breakfast, lunch and dinner eating pattern and
      hemodialysis sessions, quality of life, depression and appetite in hemodialysis
      patients.
AB  - OBJECTIVE: To evaluate the relationship between eating pattern (regular
      breakfast, lunch and dinner) and dialysis sessions, laboratory and
      sociodemographic characteristics in hemodialysis (HD) patients. MATERIALS AND
      METHODS: In this cross-sectional study eating patterns, sociodemographic,
      laboratory and clinical parameters, depressive symptoms, quality of life,
      cognitive function and appetite status were assessed. RESULTS: Eighty-two HD
      patients on morning session and 60 patients on midday HD session schedules were
      included. Ten patients had only breakfast, 17 patients had only lunch, 26
      patients had only dinner, 5 patients had breakfast and lunch but not dinner, 28
      patients had breakfast and dinner but not lunch, 29 patients had lunch and dinner
      but not breakfast, and 19 patients had neither breakfast, nor lunch, nor dinner.
      In the whole group, only 8 patients reported that they had regularly eaten
      breakfast, lunch or dinner in all days of the week. Midday HD session, better
      appetite, and higher income were independently associated with having breakfast.
      Morning HD session, better appetite score, and higher income were independently
      associated with having lunch. Morning session versus midday session, nPNA,
      presence of hypertension, and the Mental Component Summary Score of SF-36 were
      independently associated with having dinner. CONCLUSION: The majority of HD
      patients eat one or two meals per day. Having breakfast (or lunch) is associated
      with midday dialysis session (or morning dialysis session, respectively), better
      appetite, and satisfactory income. Eating dinner was associated with morning
      dialysis session, hypertension, higher protein intake and higher SF-36 mental
      component summary score.

PMID- 21965057
TI  - Promoting healthy behavior from the pulpit: clergy share their perspectives on
      effective health communication in the African American church.
AB  - African Americans continue to suffer disproportionately from health disparities
      when compared to other ethnicities (ACS 2010; CDC 2007). Research indicates that
      the church and the pastor in the African American community could be enlisted to
      increase effectiveness of health programs (Campbell et al. in Health Edu Behav
      34(6):864-880, 2007; DeHaven et al. in Am J Public Health 94(6):1030-1036, 2004).
      The objective of this study was to investigate African American pastors'
      perceptions about health promotion in the church and how these perceptions could
      serve as a guide for improving health communication targeting African Americans.
      Semi-structured interviews with African American clergy revealed that pastors
      feel strongly about the intersection of health, religion and spirituality; they
      also believe that discussing health screening and other health issues more
      frequently from the pulpit and their own personal experiences will ultimately
      impact health behavior among congregants. This study suggests that African
      American clergy see themselves as health promoters in the church and believe this
      communication (i.e., pastor-endorsed health information materials) will impact
      health behavior among underserved and minority populations. 

PMID- 21965058
TI  - Psychological distress among religious nonbelievers: a systematic review.
AB  - Studies of religious belief and psychological health are on the rise, but most
      overlook atheists and agnostics. We review 14 articles that examine differences
      between nonbelievers and believers in levels of psychological distress, and
      potential sources of distress among nonbelievers. Various forms of psychological
      distress are experienced by nonbelievers, and greater certainty in one's belief
      system is associated with greater psychological health. We found one well
      documented source of distress for nonbelievers: negative perceptions by others.
      We provide recommendations for improving research on nonbelievers and suggest a
      model analogous to Pargament's tripartite spiritual struggle to understand the
      stresses of nonbelief.

PMID- 21965059
TI  - Emissions of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/PCDFs) in
      Iran.
AB  - The aim of this study was estimation of PCDD/PCDFs emissions from various sources
      in Iran. The results indicated total PCDD/PCDFs emissions in Iran in 2010, was
      1,957 g TEQ. Of this amount, about 705.8, 0.5, 463.5, 144.1 and 643.2 g TEQ/year
      was released to air, water, land, products, and in residues, respectively. Open
      burning processes and metal production are the major contributors to be known
      environmental sources of PCDD/PCDFs that contribute to about 70% of total
      PCDD/PCDFs emissions in Iran. The results showed that total PCDD/PCDFs emissions
      in Iran per inhabitant were about 26.5 g TEQ/million that is high relatively.

PMID- 21965060
TI  - A cell-free scaffold-based cartilage repair provides improved function hyaline
      like repair at one year.
AB  - BACKGROUND: Bone marrow stimulation techniques in cartilage repair such as
      drilling are limited by the formation of fibrous to hyaline-like repair tissue.
      It has been suggested such techniques can be enhanced by covering the defect with
      scaffolds. We present an innovative approach using a polyglycolic acid (PGA)
      hyaluronan scaffold with platelet-rich-plasma (PRP) in drilling.
      QUESTIONS/PURPOSES: We asked whether (1) PRP immersed in a cell-free PGA
      hyaluronan scaffold improves patient-reported 1-year outcomes for the Knee injury
      and Osteoarthritis Score (KOOS), and (2) implantation of the scaffold in
      combination with bone marrow stimulation leads to the formation of hyaline-like
      cartilage repair tissue. PATIENTS AND METHODS: We reviewed 52 patients who had
      arthroscopic implantation of the PGA-hyaluronan scaffold immersed with PRP in
      articular cartilage defects of the knee pretreated with Pridie drilling. Patients
      were assessed by KOOS. At 9 months followup, histologic staining was performed in
      specimens obtained from five patients to assess the repair tissue quality.
      RESULTS: The KOOS subscores improved for pain (55 to 91), symptoms (57 to 88),
      activities of daily living (69 to 86), sports and recreation (36 to 70), and
      quality of life (38 to 73). The histologic evaluation showed a homogeneous
      hyaline-like cartilage repair tissue. CONCLUSIONS: The cell-free PGA-hyaluronan
      scaffold combined with PRP leads to cartilage repair and improved patient
      reported outcomes (KOOS) during 12 months of followup. Histologic sections showed
      morphologic features of hyaline-like repair tissue. Long-term followup is needed
      to determine if the cartilage repair tissue is durable. LEVEL OF EVIDENCE: Level
      IV, therapeutic study. See the Guidelines for Authors for a complete description
      of levels of evidence.

PMID- 21965061
TI  - Accuracy of measuring tape and vertebral-level methods to determine shoulder
      internal rotation.
AB  - BACKGROUND: Goniometers can be used to assess shoulder ROM with reasonable
      accuracy, but not internal rotation. Vertebral level, as determined by the hand
      behind-the-back method, is used frequently but its reproducibility is
      questionable. We therefore devised a new measuring tape-based method for
      determining vertebral level. QUESTIONS/PURPOSES: We (1) compared the accuracy of
      a measuring tape-based and conventional vertebral-level method; (2) determined
      whether BMI affects their accuracy; and (3) devised a formula for converting
      distances measured using a measuring tape to vertebral levels. PATIENTS AND
      METHODS: We assessed internal rotation in 61 patients with shoulder pain. An
      electrode was taped to the skin where the thumb reached maximally behind the
      back. The vertebral-level method involved determining the vertebral level of the
      electrode by palpating bony landmarks whereas the measuring tape method involved
      measuring the distance between the C7 spinous process and the electrode. True
      vertebral levels of the electrode were confirmed by radiography. RESULTS: In
      nonobese patients, the accuracies of the upper thoracic and lumbar-level
      measurements were better for the measuring tape method than the vertebral-level
      method (r = 0.861 and 0.700, respectively in upper thoracic; 0.913 and 0.710,
      respectively in lumbar). Patient BMI affected the accuracy of the vertebral-level
      method but not that of the measuring tape method. The distances obtained using
      the measuring tape method could be converted into vertebral-level units using the
      formula: estimated vertebral level = 0.031 * [distance between C7 spinous process
      and thumb behind back] - 0.044 * [patient height] + 7.277. CONCLUSIONS: The
      measuring tape-based method reflected shoulder internal rotation with higher
      accuracy than the vertebral-level method, and unlike the vertebral-level method,
      the measuring tape method was not affected by obesity. LEVEL OF EVIDENCE: Level
      II, diagnostic study. See Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 21965062
TI  - Receptor nomenclature guidelines.
AB  - Receptors are typically characterized via two distinct approaches: (1) the
      identification and pharmacological characterization of a receptor-mediated
      response using classical pharmacological and/or radioligand approaches in tissues
      and animal models using selective agonist and antagonist ligands, and; (2) the
      cloning and expression of proteins with structural homology to known receptors,
      the function of which is subsequently established by studying the structure
      activity relationship (SAR) of receptor-mediated responses. An additional means
      to characterize receptors proceeded, and evolved, with the structural approach,
      namely classification in terms of signal transduction mechanisms. The
      International Union of Pharmacology (IUPHAR) created guidelines and selected
      working groups for each receptor family to establish a common nomenclature
      system. Reports from those groups that have reached some degree of consensus have
      been summarized in this appendix.

PMID- 21965063
TI  - Fixation, embedding, and sectioning of tissues, embryos, and single cells.
AB  - This unit describes selected methods for fixing and sectioning various forms of
      biological materials ranging from tissues to single cells. Sections prepared
      according to these protocols can then be used to examine cell and tissue
      morphology and in studies involving in situ hybridization, immunohistochemistry,
      and enzyme histochemistry. The basic protocol describes how tissues and embryos
      can be prepared for sectioning by fixing in paraformaldehyde followed by
      embedding in wax, while an alternate protocol describes fixation of suspended or
      cultured cells. Two support protocols cover preserving and fixing organs by
      perfusion of whole animals with paraformaldehyde and a procedure for sectioning
      wax blocks of fixed tissue, plus the subsequent mounting of sections onto
      prepared or "subbed" glass slides.

PMID- 21965064
TI  - Cryosectioning.
AB  - This unit describes sample preparation and sectioning methods for frozen tissue.
      Sections of this type are used in a variety of light microscopic procedures
      including in situ hybridization immunohistochemistry, and enzyme histochemistry.

PMID- 21965065
TI  - Electrophysiological analysis of G protein-coupled receptors in mammalian
      neurons.
AB  - This unit describes general techniques that are useful for recording
      electrophysiological responses that are mediated via the activation of G-protein
      coupled receptors (GPCRs). It includes a brief description of preparations, but
      focuses primarily on experiments using hippocampal brain slice preparations.
      Techniques for the preparation of brain slices, electrodes, filling solutions,
      and the recording protocols that are suitable for assessing the activity of GPCRs
      using electrophysiological techniques are summarized, and various protocols for
      the activation of these receptors are discussed.

PMID- 21965066
TI  - Overview of cell and tissue culture techniques.
AB  - Culture preparations vary greatly in complexity, ranging from single isolated
      cells to three-dimensional histotypic cell structures. Besides cultures obtained
      directly from animal tissues (primary cultures), permanent cultures of
      continuously dividing (immortalized) cells have been established. This unit
      highlights both the advantages and disadvantages of a number in vitro approaches
      including primary cultures, continuous (permanent or immortal) cell lines, and
      contrasts culture techniques including suspension, attached (monolayer), and
      three-dimensional (aggregate) cultures in addition to explants. The basics of
      culture maintenance and propagation are covered (i.e., tissue dispersion, cell
      separation and purification, and passaging), and information is provided on the
      critical aspects of culturing cells, such as pH of the media, osmolality,
      humidity, and cell density. Also included is a troubleshooting section on how to
      cope with problems of contamination by bacteria, mycoplasma, toxic chemicals or
      foreign cell types.Culture preparations vary greatly in complexity, ranging from
      single isolated cells to three-dimensional histotypic cell structure.

PMID- 21965067
TI  - Protein tyrosine kinase activity assays.
AB  - Protein tyrosine kinases (PTKs) are ubiquitous enzymes that are integrally
      involved in the regulation of transformation mechanisms, normal and pathological
      growth, cell cycle regulation, immune responses, and a variety of intracellular
      signaling mechanisms. This rapidly growing family of enzymes is generally divided
      into two groups: receptor PTKs (with more than twelve distinct families) and
      nonreceptor PTKs (with more than nine distinct families). PTKs mediate the
      enzymatic transfer of the gamma phosphate of ATP to the phenolic groups on
      tyrosine residues to generate phosphate monoesters. In this unit, several assays
      are provided to measure the ability of PTKs to transphosphorylate protein and
      peptide substrates, and to autophosphorylate. Phosphorylation of exogenous
      substrates or autophosphorylation is detected using a 32P- or 33P-phosphorylated
      protein. Alternatively, antibodies recognizing phosphorylated tyrosine residues
      can be used to quantify PTK activity. In some cases, antibodies are available for
      context-specific phosphotyrosine residues, thereby enabling the detection of PTK
      specific substrate phosphorylation.

PMID- 21965068
TI  - Nicotinic acetylcholine receptor assays.
AB  - Nicotinic acetylcholine receptors (nAChRs) in peripheral tissues are localized
      almost exclusively to autonomic nerves and the motor end plates of striated
      musculature. Pharmacologic analyses of nicotinic receptor antagonist potencies
      can be conducted by assessing the ability of these compounds to inhibit responses
      elicited by preganglionic autonomic nerve stimulation or stimulation of the motor
      nerves innervating striated muscle in isolated tissue preparations. In addition,
      in some isolated tissues innervated by autonomic nerves, nicotinic receptor
      mediated responses can be elicited by exogenously administered agonists, and the
      effects of antagonists on these responses can be assessed using pharmacologic
      analyses. This unit describes the guinea pig trachea/esophagus preparation, in
      which nicotinic receptor pharmacology can be studied at synapses of the
      parasympathetic and sympathetic nervous system and the striated musculature of
      the esophagus. In addition, a preparation whereby the nicotinic receptors of the
      striated musculature of the diaphragm can be studied is described as are
      techniques for studying exogenous nicotinic agonist mediated effects in two
      smooth muscle preparations.Nicotinic acetylcholine receptors (nAChRs) in
      peripheral tissues are localized almost exclusively to autonomic nerves.

PMID- 21965069
TI  - Cholecystokinin (CCK) assays.
AB  - Cholecystokinin (CCK) is a peptide that acts as a peripheral hormone and as a
      central neurotransmitter. To date, two distinct receptors have been identified
      for CCK using structural and operational criteria; CCK1 and CCK2 (formerly CCKA
      and CCKB, respectively). In addition, there is the gastrin receptor found in the
      stomach which has a high structural similarity to the CCK2 receptor, but which
      displays a different pharmacology. This unit presents two methods for the
      quantification of selective agonists and antagonists at CCK1 receptors and an
      assay for CCK2 receptors. In the first tissue, the guinea-pig ileum longitudinal
      muscle with myenteric plexus, both CCK1 and CCK2 receptors are present in the
      same preparation. Each receptor is distinguished in this assay using selective
      agonists and antagonists against the unwanted receptor subtype. The second
      preparation, the guinea-pig gallbladder, is a classical preparation for studying
      CCK1 receptor-active compounds in the absence of CCK2 sites.

PMID- 21965070
TI  - Dopamine 2 (DA-2) receptor assays using sympathetic nerve terminals.
AB  - In vitro experiments using isolated atria with and without superfusion can be
      used to quantify the dopamine-2 (DA-2) receptor stimulating activity of
      compounds. This receptor mechanism decreases the amount of norepinephrine
      released from sympathetic nerve terminals by neuronal impulses. DA-2 receptor
      agonists (stimulants) are very active and induce several physiological changes,
      such as bradycardia, hypotension, lower intraocular pressure, etc. In this unit,
      tissue preparation and dopamine receptor assays are described for isolated cat
      atria with field stimulation or with superfusion, and isolated guinea pig atria
      with field stimulation.

PMID- 21965071
TI  - Models for assessing antipsychotics: antagonism of amphetamine-induced
      hyperactivity and stereotypies in mice.
AB  - All classical antipsychotics, such as chlorpromazine and haloperidol, have potent
      dopamine receptor-blocking properties. This unit describes the rat anti-Thy-1.1
      model of acute proliferative glomerulonephritis for the study of chronic renal
      insufficiency. A procedure is detailed for the induction of glomerulonephritis in
      rats as well as measurement of daily urinary excretion of protein, which is a
      convenient, primary screening tool. The unit also provides methods for assessment
      of glomerular filtration rate and effective renal plasma flow in anesthetized
      rats with anti-Thy-1.1-induced renal insufficiency.

PMID- 21965072
TI  - Models for environmentally induced eating disorders: dietary hyperphagia and
      anorexia nervosa.
AB  - The two protocols in this unit provide suggestions for constructing models of
      eating disorders that are at the opposite ends of the spectrum: dietary
      hyperphagia and anorexia nervosa. The greatest degree of dietary hyperphagia is
      induced by giving rats or mice access to a daily choice of highly palatable foods
      (e.g., chocolate or bread) in addition to their regular chow. Like humans, rats
      overeat and actually develop physiological requirements for these foods. This
      model can be used to test the effects of putative anorectic agents on both acute
      and chronic administration regimens. The second protocol describes a model of
      compulsive behavior that results in profound weight loss, which is produced by
      moderate food deprivation along with continuous access to exercise wheels.

PMID- 21965073
TI  - Overview of the use of transgenic animals in CNS drug discovery.
AB  - This overview highlights how transgenic mice, and related genetic manipulations,
      can contribute in important ways to the goal of developing novel treatments for
      neuropsychiatric disorders. A brief background of the field of drug discovery is
      covered and then new animal models of CNS disorders are discussed along with the
      topics of target validation, identification of novel targets, and functional
      genomics.

PMID- 21965074
TI  - Models of renal insufficiency: the anti-thy-1.1 model of acute proliferative
      glomerulonephritis.
AB  - This unit describes the rat anti-Thy-1.1 model of acute proliferative
      glomerulonephritis for the study of chronic renal insufficiency. A procedure is
      detailed for the induction of glomerulonephritis in rats as well as measurement
      of daily urinary excretion of protein, which is a convenient, primary screening
      tool. The unit also provides methods for assessment of glomerular filtration rate
      and effective renal plasma flow in anesthetized rats with anti-Thy-1.1-induced
      renal insufficiency.

PMID- 21965075
TI  - Isotopic assays for reporter gene activity.
AB  - This unit describes two widely used reporter systems that are based on
      radioactive detection assays. The first assay uses chloramphenicol
      acetyltransferase (CAT) activity as a measure of the level of expression of a
      transfected gene. This bacterial enzyme catalyzes the transfer of an acyl group
      from acetyl CoA to chloramphenicol. Transfected cells are harvested and lysed,
      and then acyl CoA and radioactively labeled chloramphenicol are added to cell
      lysate, and modified derivatives of the antibiotic are separated from the
      starting material. The second reporter system uses a kit to perform a simple two
      site radioimmunoassay to quantitate the amount of human growth hormone (hGH)
      secreted into culture medium by transfected cells. Medium is incubated with 125I
      labeled antibody specific for hGH, and immune complexes are collected by an
      avidin-coated bead. The quantity of hormone is determined based on comparison
      with a standard curve.

PMID- 21965076
TI  - Nonisotopic assays for reporter gene activity.
AB  - This unit describes two nonisotopic systems for reporter gene activity in cells
      transfected with the firefly luciferase.

PMID- 21965077
TI  - Use of the A. victoria green fluorescent protein to study protein dynamics in
      vivo.
AB  - Fluorescent molecules serve as valuable tools for the detection of a variety of
      biochemical phenomena. Such reagents have been employed for protein localization,
      quantitation of gene expression, detection of nucleic acids, cell sorting, and
      determination of chemical concentrations. Although fluorescence is a useful tool
      for detecting molecules within cells, its application in vivo has been limited.
      The ideal vital fluorescent tag should (1) be detectable without causing
      cytological damage, (2) be able to label a wide variety of cell types readily,
      and (3) be able to be targeted to virtually any subcellular region. The recently
      cloned green fluorescent protein (GFP) from the jellyfish Aequorea victoria is
      such a molecule. This overview describes the use of this proteinaceous
      fluorophore for in vivo observation of cellular phenomena, including applications
      and problems with the use of GFP, a discussion of mutant GFPs with altered
      fluorescence characteristics, and also some details on microscopy requirements.

PMID- 21965078
TI  - Peribiliary cysts.

PMID- 21965079
TI  - Molecular modeling study on the disassembly of dendrimers designed as potential
      antichagasic and antileishmanial prodrugs.
AB  - A molecular modeling study was carried out to investigate the most likely
      enzymatic disassembly mechanism of dendrimers that were designed as potential
      antichagasic and antileishmanial prodrugs. The models contained myo-inositol
      (core), L-malic acid (spacer), and active agents such as 3-hydroxyflavone,
      quercetin, and hydroxymethylnitrofurazone (NFOH). A theoretical approach that
      considered one, two, or three branches has already been performed and reported by
      our research group; the work described herein focused on four (models A and B),
      five, or six branches, and considered their physicochemical properties, such as
      spatial hindrance, electrostatic potential mapping, and the lowest unoccupied
      molecular orbital energy (E(LUMO)). The findings suggest that the carbonyl group
      next to the myo-inositol is the most promising ester breaking point.

PMID- 21965080
TI  - Craniofacial morphology in patients with hypophosphatemic rickets: a
      cephalometric study focusing on differences between bone of cartilaginous and
      intramembranous origin.
AB  - Hypophosphatemic rickets (HR) are diseases characterized by deficient
      mineralization of bone due to abnormal renal wasting of phosphate. Deformation of
      bony structures of cartilaginous origin has been described as a major
      characteristic in patients with HR, but little is known about the impact on bony
      structures of intramembranous origin. The aim of the present study was to
      describe the osseous morphology of the craniofacial structures in patients with
      HR compared to healthy controls, and to investigate the impact of different bone
      origin on the osseous morphology. Fifty-three patients with HR (17 males, 36
      females), aged 3-74 yrs, were included. Fifty HR patients had dominant X-linked
      disease, and in three patients no mutations were identified. A total of 79
      healthy individuals (37 males, 42 females), aged 6-79 yrs, with normal occlusion
      served as controls. Significant cephalometric differences were found between HR
      patients and controls. In HR patients, the cranial base was flattened and the
      depth of the posterior cranial fossa was decreased. The anterior height of the
      cranium, the angle nasion-sella-frontale, and the thickness of theca were
      increased. The length of the nasal bone and the height of the maxilla were
      reduced. In contrast, the vertical as well as the sagittal relation between the
      jaws were unaffected in HR patients compared to controls. In conclusion, we found
      that the cranial structures of cartilaginous origin as well as the structures of
      intramembraneous origin were affected in patients with HR.

PMID- 21965081
TI  - Restriction mapping of betaS locus among Tunisian sickle-cell patients.
AB  - OBJECTIVES: The polymorphism of the beta-globin gene haplotypes and frameworks is
      useful in the determination of the unicentric and multicentric origin of a
      mutational event. In our study, the haplotypes linked to the Tunisian beta(S)
      mutation are determined to improve our knowledge of the chromosomal background of
      the beta-globin gene in sickle-cell anemia in Tunisia. METHODS: The authors have
      investigated 242 unrelated individuals. Haplotype analysis was carried out by
      polymerase chain reaction-restriction fragment length polymorphism-based methods.
      Seven polymorphic sites in the beta-globin gene cluster were examined. The
      correlation of these various haplotypes with Hb F expression was studied.
      RESULTS: The Benin haplotype (Ben) was largely predominant (60.54%) followed by
      the Atypical haplotype A (8.43%) and Bantu (Ban) (2.71%) haplotypes. A total of
      94 chromosomes had atypical haplotypes, 78 (23.49%) had A1 [-----++], 11 (3.31%)
      had A2 [-------], and five (1.5%) had B1 [--+--++]. The Benin haplotype is
      associated with a fairly low HbF levels. CONCLUSION: The very high frequency of
      the Benin haplotype in our study suggests that the beta(S) mutation present in
      Tunisia may have originated from the Benin region and was brought to Tunisia
      along the slave trade routes. However, another atypical haplotype observed a new
      emergence in our population and could be considered as specific to Tunisian
      chromosome beta(S).

PMID- 21965082
TI  - Rasamsonia, a new genus comprising thermotolerant and thermophilic Talaromyces
      and Geosmithia species.
AB  - The phylogenetic relationship among Geosmithia argillacea, Talaromyces emersonii,
      Talaromyces byssochlamydoides and other members of the Trichocomaceae was studied
      using partial RPB2 (RNA polymerase II gene, encoding the second largest protein
      subunit), Tsr1 (putative ribosome biogenesis protein) and Cct8 (putative
      chaperonin complex component TCP-1) gene sequences. The results showed that these
      species form a distinct clade within the Trichocomaceae and Trichocoma paradoxa
      is phylogenetically most closely related. Based on phenotypic and physiological
      characters and molecular data, we propose Rasamsonia gen. nov. to accommodate
      these species. This new genus is distinct from other genera of the Trichocomaceae
      in being thermotolerant or thermophilic and having conidiophores with distinctly
      rough walled stipes, olive-brown conidia and ascomata, if present, with a scanty
      covering. Species within the genus Rasamsonia were distinguished using a
      combination of phenotypic characters, extrolite patterns, ITS and partial
      calmodulin and beta-tubulin sequences. Rasamsonia brevistipitata sp. nov. is
      described and five new combinations are proposed.

PMID- 21965083
TI  - Adding more years to the work careers of an aging workforce--what works?

PMID- 21965084
TI  - Multicentric encapsulated papillary oncocytic neoplasm of the thyroid: A case
      diagnosed by a combined cytological, histological, immunohistochemical, and
      molecular approach.
AB  - Fine-needle aspiration (FNA) diagnosis of oncocytic lesions is challenging. In
      fact, oncocytic changes occur in inflammatory, hyperplastic, and neoplastic
      settings, including both benign and malignant tumors. The rare oncocytic variant
      of papillary thyroid carcinoma (PTC), shows papillae composed by cells with large
      oncocytic granular cytoplasm featuring clear PTC nuclear features. A
      morphological similar, but biologically distinct lesion, is the encapsulated
      papillary oncocytic neoplasia. Here, we first report on FNA, its cytological
      features together with histological, immunohistochemical, and molecular
      correlates.

PMID- 21965085
TI  - The gallbladder of Uranoscopus scaber L. (teleost perciform fish) is lined by
      specialized cholecystocytes.
AB  - The gallbladder of Uranoscopus exhibits a mucosal surface layer of simple
      columnar epithelium composed of specialized cholecystocytes. The apices show
      storage and mucous secretions, typical microvilli, and very apical projections
      extending deep into the luminal contents. Many organelles and heterogeneous
      vesicles of diverse size fill the cytoplasm, including neutral mucins,
      mitochondria, peroxisomes, lysosomal bodies, and lipid-rich deposits with
      cholesterol inclusions. The fibromuscular layer shows little blood supply and
      contains scattered lymph-like walls with minute cholesterol inclusions. The
      remaining muscular, subserosal, and serosal or adventitial layers of this species
      do not show any histologic differences to those of other vertebrates. It was
      unexpected to find cholesterol inclusions in the fatty deposits of the
      cholecystocytes, similar to those noted in human cholesterolosis and in some
      forms of hypercholesterolemia, in this teleostean. In addition, aggregations of
      mitochondria and anomalous mitochondrial morphologies were found that resemble
      oncocytoma-like changes.

PMID- 21965086
TI  - Maternal depressive symptoms following autism spectrum diagnosis.
AB  - The current study examined depressive symptoms, concerning the week following
      autism spectrum diagnosis and an average of 1.4 years later, in mothers (n = 75)
      of young children diagnosed with an autism spectrum disorder (ASD). Over three
      quarters of mothers (78.7%) provided retrospective reports of clinically
      significant depressive symptoms regarding the week following their child's ASD
      diagnosis, with some 37.3% continuing to report clinically significant levels of
      depressive symptoms at follow-up. Depressive symptoms immediately following
      diagnosis were not related to initial global characteristics of child
      functioning, but were related to reported child problem behaviors and financial
      barriers at follow-up. Results of this study underscore the importance of
      attention to caregiver distress and depression within models of autism detection
      and intervention.

PMID- 21965087
TI  - Functional analysis of Waardenburg syndrome-associated PAX3 and SOX10 mutations:
      report of a dominant-negative SOX10 mutation in Waardenburg syndrome type II.
AB  - Waardenburg syndrome (WS) is an auditory-pigmentary disorder resulting from
      melanocyte defects, with varying combinations of sensorineural hearing loss and
      abnormal pigmentation of the hair, skin, and inner ear. WS is classified into
      four subtypes (WS1-WS4) based on additional symptoms. PAX3 and SOX10 are two
      transcription factors that can activate the expression of microphthalmia
      associated transcription factor (MITF), a critical transcription factor for
      melanocyte development. Mutations of PAX3 are associated with WS1 and WS3, while
      mutations of SOX10 cause WS2 and WS4. Recently, we identified some novel WS
      associated mutations in PAX3 and SOX10 in a cohort of Chinese WS patients. Here,
      we further identified an E248fsX30 SOX10 mutation in a family of WS2. We analyzed
      the subcellular distribution, expression and in vitro activity of two PAX3
      mutations (p.H80D, p.H186fsX5) and four SOX10 mutations (p.E248fsX30, p.G37fsX58,
      p.G38fsX69 and p.R43X). Except H80D PAX3, which retained partial activity, the
      other mutants were unable to activate MITF promoter. The H80D PAX3 and E248fsX30
      SOX10 were localized in the nucleus as wild type (WT) proteins, whereas the other
      mutant proteins were distributed in both cytoplasm and nucleus. Furthermore,
      E248fsX30 SOX10 protein retained the DNA-binding activity and showed dominant
      negative effect on WT SOX10. However, E248fsX30 SOX10 protein seems to decay
      faster than the WT one, which may underlie the mild WS2 phenotype caused by this
      mutation.

PMID- 21965089
TI  - Multiple external electrical cardioversions for refractory neonatal atrial
      flutter.
AB  - This report describes a case of atrial flutter in a fetal/neonatal patient who
      did not respond to adenosine, a propafenone bolus, and three electrical external
      cardioversions. A fourth direct current cardioversion after propafenone
      premedication resolved the atrial flutter. The arrhythmia did not recur with
      propafenone therapy during a 12-month follow-up period.

PMID- 21965088
TI  - Epidemiologic survey of Kawasaki disease in Jilin from 1999 through 2008.
AB  - The epidemiologic pictures of Kawasaki disease (KD) in Jilin Province of China is
      still not clear. We sent a questionnaire form and diagnostic guidelines for KD to
      the province's 32 hospitals above the county and city level with pediatric in
      patients. All patients with KD diagnosed during January 1999 through December
      2008 were recruited in this survey. The incidence of KD was 1.39 to 11.07 (5.26
      +/- 3.97) per 100,000 children under the age of 5 years between 1999 and 2008.
      The ratio of male to female was 1.96 to 1. Ages at onset ranged from 58 days to
      14 years. Patients under 5 years of age accounted of 88.73%. The disease occurred
      throughout the year, but it occurred more frequently in May to July and November.
      The most common cardiac abnormality was coronary artery dilatation (49.5%). Age
      at onset and hypoalbuminemia (<30 g/l) were selected for multivariate logistic
      regression equation. In conclusion, incidences of KD increased in Jilin Province.
      Age and gender distribution shared similarities with previous reports, and the
      seasonal distribution was different. Age and lower serum albumin were the most
      important risk factors of coronary arterial lesions (CAL) in KD. In addition,
      patients treated with steroids also had a possible heightened risk of contracting
      CAL.

PMID- 21965090
TI  - Male circumcision and human papillomavirus infection in men: a systematic review
      and meta-analysis.
AB  - BACKGROUND: We systematically reviewed the evidence for an association between
      male circumcision and Human Papillomavirus (HPV) infection and genital warts in
      men. METHODS: PubMed and Embase were searched to 15 September 2010. The measure
      of effect was the adjusted odds ratio (OR) or rate ratio (RR) when present and
      the crude estimate otherwise. Random effects meta-analyses were used to calculate
      summary measures of effect. RESULTS: We identified 23 papers about the
      association between circumcision and HPV DNA. Circumcised men were less likely to
      have prevalent genital HPV infection than uncircumcised men (summary OR, 0.57,
      95% confidence interval [CI], 0.45-0.71) with between-study heterogeneity (P
      heterogeneity = 0.006; I(2) = 50.5%; 19 studies). Similar summary associations
      were seen in clinical and methodological subgroups. The effect of circumcision
      was stronger at the glans/corona (OR, 0.47; 95% CI, 0.37-0.60) and urethra (OR,
      0.35; 95% CI, 0.12-1.05) compared with sites more distal to the foreskin. There
      was weak evidence that circumcision was associated with decreased HPV incidence
      (summary RR, 0.75, 95% CI, 0.57-0.99; 3 studies) and increased HPV clearance
      (summary RR, 1.33; 95% CI, 0.89-1.98; 3 studies) but no evidence of an
      association with prevalent genital warts (OR, 0.93, 95% CI, 0.65-1.33; 15
      studies). CONCLUSIONS: Several countries are expanding access to voluntary
      medical male circumcision to reduce HIV prevalence. This could provide additional
      benefit in reducing HPV prevalence.

PMID- 21965097
TI  - Predictors of successful extracorporeal membrane oxygenation (ECMO) weaning after
      assistance for refractory cardiogenic shock.
AB  - PURPOSE: Detailed extracorporeal membrane oxygenation (ECMO) weaning strategies
      and specific predictors of ECMO weaning success are lacking. This study evaluated
      a weaning strategy following support for refractory cardiogenic shock to identify
      clinical, hemodynamic, and Doppler echocardiography parameters associated with
      successful ECMO removal. METHODS: Hemodynamically stable patients underwent ECMO
      flow reduction trials to <1.5 L/min under clinical and Doppler echocardiography
      monitoring. When a patient had partially or fully recovered from severe cardiac
      dysfunction, tolerated the weaning trial, and had left ventricular ejection
      fraction (LVEF) >20-25% and aortic time-velocity integral (VTI) >10 cm under
      minimal ECMO support, device removal was considered. RESULTS: Among the 51
      patients (34 males, aged 54 +/- 14 years) who received ECMO for medical (n = 27),
      postcardiotomy (n = 11), or posttransplantation (n = 5) cardiogenic shock, 38
      tolerated at least one ECMO flow reduction trial and 20 were ultimately weaned.
      Compared with the 13 patients who tolerated the trial but were not deemed
      weanable, those successfully weaned had, at each ECMO flow level, higher arterial
      systolic and pulse pressures, VTI, LVEF, and lateral mitral annulus peak systolic
      velocity (TDSa). All weaned patients had aortic VTI >=10 cm, LVEF >20-25%, and
      TDSa >=6 cm/s at minimal ECMO flow support. These Doppler echocardiography
      parameters better separated weaned and nonweaned patients than any other
      parameters tested. CONCLUSIONS: Patients who tolerated a full ECMO weaning trial
      and had aortic VTI >=10 cm, LVEF >20-25%, and TDSa >=6 cm/s at minimal ECMO flow
      were all successfully weaned. However, further studies are needed to validate
      these simple and easy-to-acquire Doppler echocardiography parameters as
      predictors of subsequent ECMO weaning success in patients recovering from severe
      cardiogenic shock.

PMID- 21965098
TI  - Tolstoy on transparency and authority in end-of-life decision-making.

PMID- 21965096
TI  - Forgoing life support: how the decision is made in European pediatric intensive
      care units.
AB  - PURPOSE: To determine how decisions to forgo life support are made in European
      pediatric intensive care units (PICUs). METHODS: A multicenter, prospective
      study, the Eurydice II study, among 45 PICUs: 20 in France, 21 in
      Northern/Western (N/W) European countries, and 4 in Eastern/Central (E/C) Europe.
      Data were collected between November 2009 and April 2010 through a questionnaire.
      RESULTS: The decision to forgo life-sustaining treatment was made in 166 (40.6%)
      out of 409 deceased children (median 42.9%, France 38.2%, N/W European countries
      60.0%, E/C European countries 0%; P < 0.001). In the E/C group, more patients
      died after cardiopulmonary resuscitation (CPR) failure than after forgoing life
      support (P < 0.001). In all PICUs, caregivers discussed the decision during a
      formal meeting, after which the medical staff made the final decision. The
      decision was often documented in the medical record (median 100%). The majority
      of the parents were informed of the final decision and were at the bedside during
      their child's death (median 100%). Decision to forgo life-sustaining treatment
      occurred in 40.6% of children, compared with 33% in Eurydice I. A high percentage
      of parents from France were now informed about the meeting and its conclusion as
      compared with Eurydice I (median 100%). CONCLUSIONS: The results of this study
      and comparison with the Eurydice I study (2002) show a trend towards
      standardization of end-of-life practices across N/W European countries and France
      in the past decade.

PMID- 21965099
TI  - Variability in usual care mechanical ventilation for pediatric acute lung injury:
      the potential benefit of a lung protective computer protocol.
AB  - PURPOSE: Although pediatric intensivists claim to embrace lung protective
      ventilation for acute lung injury (ALI), ventilator management is variable. We
      describe ventilator changes clinicians made for children with hypoxemic
      respiratory failure, and evaluate the potential acceptability of a pediatric
      ventilation protocol. METHODS: This was a retrospective cohort study performed in
      a tertiary care pediatric intensive care unit (PICU). The study period was from
      January 2000 to July 2007. We included mechanically ventilated children with
      PaO(2)/FiO(2) (P/F) ratio less than 300. We assessed variability in ventilator
      management by evaluating actual changes to ventilator settings after an arterial
      blood gas (ABG). We evaluated the potential acceptability of a pediatric
      mechanical ventilation protocol we adapted from National Institutes of
      Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) Acute Respiratory
      Distress Syndrome (ARDS) Network protocols by comparing actual practice changes
      in ventilator settings to changes that would have been recommended by the
      protocol. RESULTS: A total of 2,719 ABGs from 402 patients were associated with
      6,017 ventilator settings. Clinicians infrequently decreased FiO(2), even when
      the PaO(2) was high (>68 mmHg). The protocol would have recommended more positive
      end expiratory pressure (PEEP) than was used in actual practice 42% of the time
      in the mid PaO(2) range (55-68 mmHg) and 67% of the time in the low PaO(2) range
      (<55 mmHg). Clinicians often made no change to either peak inspiratory pressure
      (PIP) or ventilator rate (VR) when the protocol would have recommended a change,
      even when the pH was greater than 7.45 with PIP at least 35 cmH(2)O. CONCLUSIONS:
      There may be lost opportunities to minimize potentially injurious ventilator
      settings for children with ALI. A reproducible pediatric mechanical ventilation
      protocol could prompt clinicians to make ventilator changes that are consistent
      with lung protective ventilation.

PMID- 21965100
TI  - Acquired von Willebrand syndrome in patients with extracorporeal life support
      (ECLS).
AB  - PURPOSE: Extracorporeal life support (ECLS) is used for patients with refractory
      heart failure with or without respiratory failure. This temporary support is
      provided by blood pumps which are connected to large vessels. Bleeding episodes
      are a typical complication in patients with ECLS. Recently, several studies
      illustrated that acquired von Willebrand syndrome (AVWS) can contribute to
      bleeding tendencies in patients with long-term ventricular assist devices (VAD).
      AVWS is characterized by loss of the high molecular weight (HMW) multimers of von
      Willebrand factor (VWF) as a result of high shear stress and leads to impaired
      binding of VWF to platelets and to subendothelial matrix. Since ECLS and VAD
      share several features, we investigated patients with ECLS for AVWS. METHODS: We
      analyzed 32 patients with ECLS and 19 of them without support. To diagnose AVWS,
      ratios of ristocetin cofactor activity (VWF:RCo) and collagen binding capacity
      (VWF:CB) to VWF antigen (VWF:Ag) were employed in conjunction with multimeric
      analysis. RESULTS: Reduced VWF:RCo/VWF:Ag ratios were identified in 28 ECLS
      patients. Furthermore, VWF:CB/VWF:Ag ratios were decreased in 31 patients. HMW
      multimers of VWF were missing in the same 31 patients. Thus, 31 of 32 ECLS
      patients presented with AVWS. Twenty-two of the 32 patients suffered from
      bleeding complications. Without support, AVWS was not detectable in any analyzed
      patient. CONCLUSION: Our data indicate that AVWS is a typical disorder in
      patients with ECLS. We hypothesize that AVWS could contribute to aggravation of
      bleeding tendencies in ECLS patients.

PMID- 21965102
TI  - A case of uncommon acute respiratory distress syndrome: from shear stress to
      economic stress.

PMID- 21965101
TI  - Impact of an embedded simulation team training programme in a paediatric
      intensive care unit: a prospective, single-centre, longitudinal study.
AB  - PURPOSE: To evaluate the impact of an embedded simulation-based team training
      programme on perceived performance and to compare the effect over different
      phases of the programme. METHODS: This was a prospective, single-centre,
      longitudinal study over the first 2 years of the programme. A total of 219
      multidisciplinary health-care professionals participated in simulation sessions,
      followed by anonymous evaluation questionnaires. The programme was divided into
      three different phases: introductory (first 6 months), intermediate (second 6
      months) and established phase (second year). RESULTS: A total of 88.7% of
      participants evaluated the impact on overall practice as effective, 56.5%
      reported a highly effective impact. A total of 90.9% (391/430) of questions on
      non-technical skills (communication and teamwork) showed an effective impact,
      55.6% a highly effective impact, whereas only 70.2% (262/373) of questions on
      technical skills showed an effective impact. There was a significant (p < 0.001)
      increased score for effective impact in all categories between the introductory
      and intermediate phase, which was maintained throughout the established phase.
      Overall, 72.7% of the participants felt more confident to attend a future
      critical event, 32.5% were highly confident. In the longitudinal analysis there
      was a stepwise significant (p < 0.05) increase of confidence of participants. In
      a subgroup analysis (n = 143) there was a significant (p < 0.001) higher
      confidence in participants who had attended at least 3 sessions (90.7 vs. 61%).
      CONCLUSION: There is a 6- to 12-month learning curve in the implementation of an
      embedded multidisciplinary team training programme. Repeated exposure to
      simulation is most beneficial to crisis resource management training and single,
      isolated exposure may not be sufficient.

PMID- 21965103
TI  - Insufficient performance of serum cystatin C as a biomarker for acute kidney
      injury of postrenal etiology.

PMID- 21965105
TI  - Functional outcomes after radiotherapy or laser surgery in early glottic
      carcinoma: a systematic review.
AB  - BACKGROUND: Early glottic carcinoma is treated with laser surgery or
      radiotherapy, but which treatment has better functional outcomes is unclear. This
      systematic review compared functional outcomes (voice, swallowing, quality of
      life [QOL]) in more extended T1a and limited T2 tumors (1) between treatments and
      (2) between greater and lesser laser resections. METHODS: A systematic literature
      search covered relevant databases from 1990 to 2009, combining all
      patient/problem, intervention, comparison, outcome (PICO) keyword variations.
      RESULTS: A total of 19 papers met the inclusion criteria, all of which were level
      IV evidence. Papers reported only voice and QOL. Heterogeneity of outcome
      measures prevented data pooling. Uncertainty about tumor comparability (depth,
      extent) between the 2 treatments, small subject numbers, and poor-quality
      reporting hindered interpretation. CONCLUSIONS: To allow comparison of laser
      surgery versus radiotherapy, a standardized method is needed that accurately
      measures tumor extent and depth. Agreement on functional outcome measures is
      necessary to allow comparison of treatments and resection types. Multicenter
      studies should be encouraged to guarantee adequate subject numbers.

PMID- 21965104
TI  - The younger siblings of childbearing adolescents: parenting influences on their
      academic and social-emotional adjustment.
AB  - The younger siblings of childbearing adolescents have poorer school outcomes and
      exhibit more internalizing and externalizing problems compared to their peers
      without a childbearing sister. We test a model where living with an adolescent
      childbearing sister constitutes a major family stressor that disrupts mothers'
      parenting and well-being, and through which, adversely affect youths' adjustment.
      Data came from 243 Latino younger siblings (62% female, M age 13.7 years) and
      their mothers, 121 of whom lived with a childbearing adolescent sister and 122 of
      whom did not. Individual fixed-effects models controlled for earlier measures of
      each respective model construct, thereby reducing omitted variable bias from pre
      existing group differences. Results show that, for boys, the relationship between
      living with a childbearing adolescent sister and youth outcomes was sequentially
      mediated through mothers' stress and parenting (i.e., monitoring and nurturance).
      For girls, however, the relationship was mediated through mothers' monitoring
      only. Findings elucidate the within-family processes that contribute to the
      problematic outcomes of youth living with childbearing adolescent older sisters.

PMID- 21965106
TI  - Microscope objectives.
AB  - The objective is the most crucial image-forming component of a microscope. A
      knowledge of the many types of objectives available and their characteristics is
      critical to the selection of appropriate objectives for image cytometry. This
      unit discusses aberrations in image formation and their correction, construction,
      and types of objectives, and objectives for other microscopy applications,
      explaining the advantages and limitations of each one.

PMID- 21965107
TI  - Light microscopy digital imaging.
AB  - This unit presents an overview of digital imaging hardware used in light
      microscopy. CMOS, CCD, and EMCCDs are the primary sensors used. The strengths and
      weaknesses of each define the primary applications for these sensors. Sensor
      architecture and formats are also reviewed. Color camera design strategies and
      sensor window cleaning are also described in the unit.

PMID- 21965108
TI  - Assessing mitochondrial redox status by flow cytometric methods: vascular
      response to fluid shear stress.
AB  - Mitochondria are an important source of superoxide production contributing to
      physiological and pathological responses, including vascular oxidative stress
      that is relevant to cardiovascular diseases. Vascular oxidative stress is
      intimately linked with pro-inflammatory states and atherosclerosis. Oxidized low
      density lipoprotein (OxLDL) modulates intracellular redox status and induces
      apoptosis in endothelial cells. Hemodynamic, specifically, fluid shear stress
      imparts both biomechanical and metabolic effects on vasculature. Mitochondria are
      an important source of superoxide production contributing to vascular oxidative
      stress with relevance to cardiovascular diseases. We hereby present biophysical
      and biochemical approaches, including fluorescence-activated cell sorting, to
      assess the dynamics of vascular redox status.

PMID- 21965109
TI  - Effect of organic zinc, manganese, copper, and selenium chelates on colostrum
      production and reproductive and lameness indices in adequately supplemented
      Holstein cows.
AB  - The current study aimed to investigate if different sources of supplemental zinc
      (Zn), manganese (Mn), copper (Cu), and selenium (Se) fed to dry and lactating
      dairy cows affect reproductive performance, lameness status, and colostrum
      production. The experiment was carried out on 60 multiparous non-lactating
      Holstein cows in a commercial dairy herd. The cows received randomly mineral
      mixtures in three treatment groups containing inorganic, 25% organic-75%
      inorganic, or 50% organic-50% inorganic forms of Zn, Mn, Cu, and Se starting from
      approximately 3 weeks prior to calving up to 90 days postpartum. Supplements were
      included in rations and fed twice a day. Reproductive parameters including days
      to first service, days to first estrus, service per conception, and conception
      rate were investigated. After parturition, colostrum production, composition, and
      immunoglobulin G(1) concentration were determined. Lameness, as an indicator of
      trace minerals deficiency, was evaluated in a five-score scale. The source of
      mineral supplement only numerically improved the assessed parameters excluding
      colostrum fat, protein, and ash percent. The organic form of supplements did not
      significantly affect reproductive performance, lameness score, or colostrum
      production.

PMID- 21965111
TI  - Comparative assessment of essential and toxic metals in the blood of rheumatoid
      arthritis patients and healthy subjects.
AB  - The present study deals with the comparative evaluation of essential and toxic
      metals in rheumatoid arthritis and healthy donors. Blood samples collected from
      rheumatoid arthritis patients and healthy subjects were analysed for selected
      essential and toxic metals (Ca, Mg, Fe, Zn, Cu, Co, Mn, Cr, Cd and Pb). The
      samples were digested in nitric acid and perchloric acid mixture, followed by
      quantification of the metals using atomic absorption spectrometry. Mean levels of
      Ca, Mg, Fe and Zn were significantly higher in the blood of healthy donors;
      however, elevated levels of Cd, Co, Cr, Cu and Pb were observed in blood of the
      patients. The correlation coefficients among the selected metals in the blood of
      arthritis patients were significantly different compared with the healthy
      counterparts. Multivariate cluster analysis revealed mutual apportionment of the
      essential and toxic metals in blood of the patients, whereas, in controls, the
      essential and toxic metals revealed diverse apportionment. Variations in the
      metal levels with gender, residence and smoking habits were also evaluated in
      both donor groups. Relative distribution, correlation and apportionment of the
      essential and toxic metals in the blood of the patients were significantly
      different than of controls.

PMID- 21965112
TI  - A gene expression-based screening system for compounds influencing
      differentiation of mouse embryonic stem cells.
AB  - Low molecular weight compounds have been shown to be useful for controlling stem
      cells, and various high-throughput screening systems have been developed for
      identifying compounds that regulate the differentiation of stem cells. However,
      the effects of such compounds on stem cell differentiation are usually evaluated
      by assessing a single parameter, which is insufficient for proper monitoring of
      the cellular status. In this study, to classify a number of compounds, the
      authors established a gene expression-based screening system using mouse
      embryonic stem (ES) cells that monitored multiple parameters. ES cells were
      differentiated into three germ layers by embryoid body formation and then treated
      with the test compounds. Next, cellular changes were assessed by analyzing the
      expression of multiple genes with the multiplex quantitative reverse
      transcriptase polymerase chain reaction. By screening a library of
      pharmacologically active compounds with this system, the authors were able to
      classify 52 compounds that influenced the gene expression profile of ES cells.
      They also found that some compounds identified by screening could enhance
      osteogenic or adipogenic differentiation of human mesenchymal stem cells. These
      results indicate that the screening system is effective for identifying compounds
      involved in regulating the differentiation of both ES cells and adult stem cells.

PMID- 21965113
TI  - Screening assays for epigenetic targets using native histones as substrates.
AB  - In the past years, a lot of attention has been given to the identification and
      characterization of selective and potent inhibitors of chromatin-modifying
      enzymes to better understand their specific role in transcriptional regulation.
      As aberrant histone methylation is involved in different pathological processes,
      the search for methyltransferase and demethylase inhibitors has emerged as a
      crucial issue in current medicinal chemistry research. High-throughput in vitro
      assays are important tools for the identification of new methyltransferase or
      demethylase inhibitors. These usually use oligopeptide substrates derived from
      histone sequences, although in many cases, they are not good substrates for these
      enzymes. Here, the authors report about the setup and establishment of in vitro
      assays that use native core histones as substrates, enabling an assay environment
      that better resembles native conditions. They have applied these substrates for
      the known formaldehyde dehydrogenase assay for the histone demethylase LSD1 and
      have established two new antibody-based assays. For LSD1, a heterogeneous assay
      format was set up, and a homogeneous assay was used for the characterization of
      the arginine methyltransferase PRMT1. Validation of the system was achieved with
      reference inhibitors in each case.

PMID- 21965114
TI  - Epigenetic drug discovery: targeting DNA methyltransferases.
AB  - Epigenetic modification of DNA leads to changes in gene expression. DNA
      methyltransferases (DNMTs) comprise a family of nuclear enzymes that catalyze the
      methylation of CpG dinucleotides, resulting in an epigenetic methylome
      distinguished between normal cells and those in disease states such as cancer.
      Disrupting gene expression patterns through promoter methylation has been
      implicated in many malignancies and supports DNMTs as attractive therapeutic
      targets. This review focuses on the rationale of targeting DNMTs in cancer, the
      historical approach to DNMT inhibition, and current marketed hypomethylating
      therapeutics azacytidine and decitabine. In addition, we address novel DNMT
      inhibitory agents emerging in development, including CP-4200 and SGI-110, analogs
      of azacytidine and decitabine, respectively; the oligonucleotides MG98 and
      miR29a; and a number of reversible inhibitors, some of which appear to be
      selective against particular DNMT isoforms. Finally, we discuss future
      opportunities and challenges for next-generation therapeutics.

PMID- 21965115
TI  - [Arguments against pressure-lowering treatment of ocular hypertension.
      Prophylactic treatment is unnecessary].
AB  - The main argument against a pressure-lowering treatment for patients with ocular
      hypertension (OHT) is the principle of "first do no harm". The imprecision of
      intraocular pressure (IOP) measurements and the fact that increased IOP is only a
      risk factor for glaucoma raise major doubts on a clinical definition of OHT. The
      use of IOP-lowering treatment in the absence of functional or morphological
      glaucomatous changes should only be initiated if the IOP is very high (>32 mmHg).
      If the IOP is between 21 and 32 mmHg the glaucoma conversion risk of the
      individual patient should be estimated. The risk factors as proven in major
      prospective trials (OHTS/EGPS) should be assessed using the risk calculator. Only
      patients with a high risk (>13%) of conversion profit from prophylactic IOP
      lowering treatment. For all patients with intermediate or low risk of conversion
      the potential side-effects (local and systemic) of the treatment outweigh the
      possible benefit, so that the principle of "watchful waiting" is the best for
      patients with OHT. If morphological or functional progression is observed IOP
      lowering treatment should be started immediately.

PMID- 21965116
TI  - Immunodeficiency in Vici syndrome: a heterogeneous phenotype.
AB  - Vici syndrome is a rare congenital multisystem disorder characterized by agenesis
      of the corpus callosum, hypotonia, developmental delay, hypopigmentation,
      cataract, cardiomyopathy, and immunological abnormalities. Recurrent infections,
      mainly affecting the respiratory tract, have been reported in the majority of
      cases, representing an important risk factor for morbidity and mortality. The
      immunological phenotype of patients is extremely variable, ranging from a
      combined immunodeficiency to nearly normal immunity. We report on a new patient
      with Vici syndrome, in whom we have extensively investigated immunological
      features. Despite a mild impairment of the cellular compartment, a defect of
      humoral immunity was found, requiring treatment with intravenous immunoglobulin.
      A wider knowledge of immune system abnormalities of Vici syndrome will help to
      plan strategies for treatment and prevention of infections, such as
      immunoglobulin replacement and antimicrobial prophylaxis, resulting in improved
      survival rates.

PMID- 21965117
TI  - Syndrome evaluation in traditional Chinese medicine using second-order latent
      variable model.
AB  - The syndrome is one of the most important concepts and ingredients in the
      theoretical and clinical research of traditional Chinese medicine (TCM). TCM
      doctors believe that all diseases are caused by an imbalance in the patient's
      body, which is called syndrome. All the therapies and formulas in TCM are decided
      according to the patients' syndrome situation. To quantitatively evaluate the
      level of syndrome, many statistical methodologies have been discussed in recent
      years. In this article, we introduce a second-order latent variable model to
      evaluate the level of patients' syndrome with many clinical symptoms. An
      objective evaluation score can be easily derived by the proposed model, with a
      high speed of convergence and without joint-distribution assumption. We
      illustrate the application of this model by an analysis of premenstrual disorder
      syndrome of liver-qi invasion syndrome evaluation research.

PMID- 21965118
TI  - EEG spectral analysis on Muslim prayers.
AB  - This study investigated the proposition of relaxation offered by performing the
      Muslim prayers by measuring the alpha brain activity in the frontal (F3-F4),
      central (C3-C4), parietal (P3-P4), and occipital (O1-O2) electrode placements
      using the International 10-20 System. Nine Muslim subjects were asked to perform
      the four required cycles of movements of Dhuha prayer, and the EEG were
      subsequently recorded with open eyes under three conditions, namely, resting,
      performing four cycles of prayer while reciting the specific verses and
      supplications, and performing four cycles of acted salat condition (prayer
      movements without any recitations). Analysis of variance (ANOVA) tests revealed
      that there were no significant difference in the mean alpha relative power
      (RP(alpha)) between the alpha amplitude in the Dhuha prayer and the acted
      conditions in all eight electrode positions. However, the mean RP(alpha) showed
      higher alpha amplitude during the prostration position of the Dhuha prayer and
      acted condition at the parietal and occipital regions in comparison to the
      resting condition. Findings were similar to other studies documenting increased
      alpha amplitude in parietal and occipital regions during meditation and mental
      concentration. The incidence of increased alpha amplitude suggested
      parasympathetic activation, thus indicating a state of relaxation. Subsequent
      studies are needed to delineate the role of mental concentration, and eye focus,
      on alpha wave amplitude while performing worshipping acts.

PMID- 21965119
TI  - The P300-based, complex trial protocol for concealed information detection
      resists any number of sequential countermeasures against up to five irrelevant
      stimuli.
AB  - We previously tested the P300-based Complex Trial protocol for deception
      detection against 2 and 4 countered of 4 irrelevant stimuli. The protocol
      detected 90-100% of these subjects with <10% false positives. We have also shown
      that Reaction Time (RT) to the first trial stimulus is increased (group effect)
      with countermeasure use. We also reported a new P900 component associated with
      countermeasure use when 2 of 4 irrelevants are countered. In the present study we
      report data from 4 new groups and re-present for comparison previously collected
      data to have 7 groups: an innocent control, a guilty group not using
      countermeasures, and 5 guilty/countermeasure groups who counter from 1 to all 5
      stimuli presented (4 irrelevants plus a probe). Subjects were detected at rates
      varying from 92 to 100% in the 6 guilty groups (n = 12 or 13 per group). There
      was 1 false positive in 13 innocent subjects. Additionally, 41 of 60 CM users
      were identified with RT as using countermeasures. P900 appeared in the 2 groups
      using 2 and 3 countermeasures.

PMID- 21965120
TI  - Nodular sclerosing classical Hodgkin lymphoma masquerading as acute suppurative
      necrotizing lymphadenitis.
AB  - The diagnosis of nodular sclerosing classical Hodgkin lymphoma (NSCHL) by fine
      needle aspiration (FNA) biopsy has historically been a diagnostic challenge due
      to the usual paucicellularity of the specimen. This case report, and other
      previously published reports, suggests that there is another facet to the
      potentially challenging diagnosis of this particular variant of Hodgkin lymphoma
      (HL): the presence of suppurative-necrotizing changes mimicking an infectious
      etiology. The patient presented here underwent FNA biopsy of an acutely enlarged
      supraclavicular lymph node and cytologic smears showed marked acute inflammation
      in a background of necrosis. A diagnosis of infectious suppurative lymphadenitis
      was made at that time. After a negative infectious work-up with infectious
      disease consultation, an excisional biopsy was performed and the patient was
      definitively diagnosed with NSCHL. The presence of neoplastic Hodgkin and Reed
      Sternberg cells in the purulent exudate was minimal and only appropriately
      identified after retrospective review. This particular subtype of classical HL
      represents a potential pitfall in FNA biopsy cytology. Consequently, the
      cytopathologist and surgeon should always consider this entity in the
      differential diagnosis of a suppurative, lymphadenitis-like aspirate, and pursue
      repeat FNA or an excisional biopsy if there is any clinical index of suspicion.

PMID- 21965121
TI  - Multiple sclerosis typical clinical and MRI findings in a patient with HIV
      infection.
AB  - BACKGROUND: Multiple sclerosis (MS) is a demyelinating disease seldom included in
      the differential diagnosis of leukoencephalopathy in HIV-positive patients.
      METHODS: We describe the clinical findings and laboratory results of a 43-year
      old male with HIV infection and MS, and reviewed 11 more cases reported in the
      literature. RESULTS: The first episode of MS occurred either during or after the
      recognition of the HIV infection except in the few cases reported in 1989. There
      has been a very strong male predominance. Age at onset was between 30 and 40
      years old. The most common clinical course was relapsing and remitting. Most of
      the cases had a normal CD4+ cell count, usually exceeding 500 cells/mm(3).
      Despite that CD4+ cell counts were invariable high, all the patients had multiple
      tests to rule out opportunistic infections and HIV-associated illness. The
      clinical suspicion of MS was only considered after ruling out other opportunistic
      infections and was supported with brain imaging showing multiple white matter
      evanescent lesions, the presence of black holes, and a high myelin basic protein
      titer in the CSF. CONCLUSIONS: MS is usually considered late in patients with
      HIV. A typical MS course with suggestive MRI lesions and absence of severe immune
      suppression should suggest the diagnosis. It is possible that as with other MS
      patients, earlier initiation of specific treatments for MS will prevent the high
      burden of the disease and disability in these patients, but stronger evidence for
      specific recommendations remains to be obtained.

PMID- 21965123
TI  - Ontogeny and disease responses of Langerhans-like cells in lymphoid tissues of
      salmonid fish.
AB  - The ontogeny and disease responses of Langerhans-like cells within lymphoid
      tissues of Atlantic salmon, Salmo salar, and rainbow trout, Oncorhynchus mykiss,
      were investigated. These cells were studied in situ with the use of two markers:
      the ultrastructural presence of Birbeck-like granules and immunohistochemistry
      with an antibody against human langerin/CD207 that cross-reacts with salmonid
      tissues. The appearance of Birbeck-like granules was observed in rainbow trout at
      2 weeks post-hatch (PH) in the thymus and anterior kidney prior to the
      development of the spleen. Spleen first appeared at 3 weeks PH in both Atlantic
      salmon and rainbow trout, and Birbeck-like granules were observed within cells of
      the newly developed spleens. The cross-reactivity of langerin as seen by
      immunohistochemistry was not clearly observed in kidney and spleen until 9 weeks
      PH, when a strong cytoplasmic reaction was observed. To study langerin-positive
      cells in spleen and kidney during disease, microsporidial gill disease (MGD) in
      rainbow trout was used as a known disease model inducing a strong cell-mediated
      adaptive immune response. Langerin-positive cells in healthy fish were seen
      predominantly in the spleen, and only low numbers were present in the anterior
      kidney. During MGD, langerin-positive cell numbers were elevated in the anterior
      kidney and were significantly higher during 5, 6, and 10 weeks post-exposure (PE)
      compared with healthy control tissue. During MGD, the distribution of langerin
      positive cells in the spleen and anterior kidney shifted from having
      significantly higher numbers of cells in the spleen than in the kidney in
      controls and at 1 and 4 weeks PE to having a similar distribution of the cells in
      the two organs at 2, 3, 5, and 6 weeks PE. By 10 weeks PE, significantly higher
      numbers of langerin-positive cells occurred in the anterior kidney compared with
      the spleen.

PMID- 21965122
TI  - Clinical contributors to cerebral white matter integrity in HIV-infected
      individuals.
AB  - HIV-infected people frequently exhibit brain dysfunction characterized by
      preferential damage to the cerebral white matter. Despite suppressed viral load
      and reconstituted immune function afforded by combination antiretroviral therapy
      (CART), brain dysfunction continues to be observed even in medically stable
      individuals. To provide insight into the etiology of HIV-associated brain
      dysfunction in the CART era, we examined the effects of HIV disease markers,
      antiretroviral treatment, hepatitis C (HCV) coinfection, and age on DTI measures
      of white matter integrity in a cohort of 85 individuals aged 23 to 65 years with
      chronic HIV infection. Fractional anisotropy and mean diffusivity were derived
      from 29 cerebral white matter regions, which were segmented on each individual
      brain using a high-resolution T1-weighted image and registered to diffusion
      images. Significant effects of clinical variables were found on white matter
      abnormalities in nearly all brain regions examined. Most notably, HCV coinfection
      and older age were associated with decreased anisotropy or increased diffusivity
      in the majority of brain regions. Individuals with higher current CD4 levels
      exhibited higher anisotropy in parietal lobe regions, while those undergoing
      antiretroviral treatment exhibited higher anisotropy in temporal lobe regions.
      The observed diffuse pattern of white matter injury suggests that future
      neuroimaging studies should employ methodologies that are not limited to
      circumscribed regions of interest. The current findings underline the
      multifactorial nature of HIV-associated brain dysfunction in the CART era, and
      the importance of examining the effects of HIV disease in the context of other
      comorbidities, in particular HCV coinfection and aging.

PMID- 21965124
TI  - Plasmin generation and fibrinolysis in pediatric patients undergoing
      cardiopulmonary bypass surgery.
AB  - This prospective, single-centre cohort study aimed to evaluate plasmin generation
      and fibrinolysis during and after cardiopulmonary bypass (CPB) surgery in a
      cohort of children up to 6 years of age. Blood samples were drawn at eight time
      points: after induction of anesthesia, before unfractionated heparin (UFH), after
      UFH, after initiation of bypass, before protamine, after protamine, after chest
      closure, and 6 h after chest closure. The study identified an increase in
      fibrinolysis during CPB and particularly up to 6 h afterward in children. This
      could be the mechanism for the significant bleeding events observed in this young
      population after CPB. This study establishes the foundation for future studies in
      this area, particularly those focusing on clinical outcomes after CPB surgery.

PMID- 21965125
TI  - Changes in hemodynamic parameters and cerebral saturation during supraventricular
      tachycardia.
AB  - Induced supraventricular tachycardia (SVT) during electrophysiology studies (EPS)
      can be associated with hemodynamic changes. Traditionally, invasive arterial
      blood pressure has been used for continuous monitoring of these changes. This
      prospective study evaluated the efficacy of near-infrared spectroscopy (NIRS)
      monitoring during SVT. The use of NIRS has expanded with evidence of its accuracy
      and benefit in detecting cerebral hypoperfusion. This study aimed first to
      determine the hemodynamic changes associated with electrophysiology testing for
      SVT and second to determine whether the hemodynamic changes are associated with
      similar changes in the cerebral saturation as determined by NIRS. The study
      enrolled 30 patients 5-20 years of age with a history of SVT who underwent an
      EPS. The demographic data included age, gender, weight, height, and type of SVT.
      Hemodynamic data (invasive blood pressure and heart rate), NIRS, bispectral index
      (BIS), end-tidal carbon dioxide, and pulse oximetry were collected before and
      during three episodes of induced SVT. The linear correlation coefficient (r) was
      measured to calculate the relationship of the changes in systolic blood pressure
      (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) to the
      changes in NIRS values during the SVT episodes. Data from 22 patients were
      collected. The induction of SVT was associated mainly with a change in SBP and a
      less prominent change in DBP and MAP from baseline. The changes in hemodynamic
      status were associated with minimal changes in cerebral saturations, as evidenced
      by an average absolute change in NIRS of <1 from baseline value. The changes in
      hemodynamics were correlated linearly with cerebral saturation. Changes in SBP,
      DBP, and MAP were correlated positively with changes in NIRS, as denoted by (r)
      values of 0.52, 0.57, and 0.67 respectively, and a P value less than 0.05 for all
      three association tests. Induction of SVT during electrophysiology testing is
      associated with hemodynamic changes, mainly in SBP. In this study, these
      hemodynamic changes resulted in a minimal decrease in cerebral perfusion, as
      evidenced by minimal changes in the cerebral saturation measured by NIRS (0.7%
      from baseline). Although the changes in the cerebral saturation were minimal,
      these changes were linearly correlated with the changes in the hemodynamics. This
      study is the first to demonstrate the possible application of NIRS monitoring
      during EPS and to document that despite changes in the hemodynamic status, the
      changes in cerebral oxygenation are minimal, thereby confirming the safety of EPS
      for SVT.

PMID- 21965126
TI  - Effects of patient education and progressive muscle relaxation alone or combined
      on adherence to continuous positive airway pressure treatment in obstructive
      sleep apnea patients.
AB  - PURPOSE: The purpose of this study is to explore the effects of patient education
      and progressive muscle relaxation (PMR) alone or combined on adherence to
      continuous positive airway pressure (CPAP) treatment in obstructive sleep apnea
      (OSA) patients. METHODS: One hundred and fifty-two Han Chinese OSA patients were
      randomly assigned to a control group (C), an education group (E), a PMR group
      (P), and an education + PMR group (E + P), with 38 patients each group. The
      adherence to CPAP was defined as 4 or more hours of CPAP usage per night and at
      least 9 of each 14 nights of ventilator use. The CPAP adherence rates, cumulative
      patient dropout rates, CPAP usage, and scores of daytime sleepiness, sleep
      quality, anxiety, and depression were compared among the groups at 4, 8, and 12
      weeks of intervention. RESULTS: All study groups were comparable in baseline
      characteristics. Group E + P showed significant improvement in CPAP adherence,
      daytime sleepiness, and sleep quality compared with group C at 4, 8, and 12 weeks
      of intervention. Compared with group C, group E only showed significant
      improvement in CPAP adherence, daytime sleepiness, and sleep quality at 4 weeks
      of intervention, while group P showed no significant improvement over time.
      Scores of anxiety and depression were significantly improved in group E + P
      compared with group C at 12 weeks of intervention. CONCLUSIONS: Combined
      intervention with patient education and PMR can significantly improve CPAP
      adherence in OSA patients for at least 12 weeks. The intervention paradigm may
      serve as an important reference for future studies on CPAP adherence.

PMID- 21965127
TI  - Arterial head vascularization cartographies of normal metencephalic dogs using
      magnetic resonance angiography.
AB  - The aim of our study was to establish head arterial cartographies-useful for the
      diagnosis of brain diseases leading to cerebral vascular modifications-by means
      of magnetic resonance angiography (MRA). Casts of the arterial vascular brain
      system were used to corroborate the MRA results as they can be easily rotated in
      nonvirtual three-dimensions and give an accurate view of the arteries calibre and
      origin. Two types of 3T MRA images were used: three-dimensional fast low-angle
      shot (3D-FLASH) acquisition sequenced every 20 s, paired with injection of a
      paramagnetic contrast medium, and three-dimensional time-of-flight (3D-TOF)
      acquisition sequenced every 300 s. 3D-FLASH acquisition gives very accurate
      images of the cerebral arteries and veins, but must be used with care in
      debilitated animals. 3D-TOF acquisition is less accurate and gives only images of
      the main cerebral arteries without showing the venous system. It is, however, a
      viable diagnostic method for monitoring vascular lesions (e.g., cerebral
      hemorrhages).

PMID- 21965128
TI  - Establishment of a novel human myeloid leukemia cell line, AMU-AML1, carrying
      t(12;22)(p13;q11) without chimeric MN1-TEL and with high expression of MN1.
AB  - In this study, we established and analyzed a novel human myeloid leukemia cell
      line, AMU-AML1, from a patient with acute myeloid leukemia with multilineage
      dysplasia before the initiation of chemotherapy. AMU-AML1 cells were positive for
      CD13, CD33, CD117, and HLA-DR by flow cytometry analysis and showed a single
      chromosomal abnormality, 46, XY, t(12;22)(p13;q11.2), by G-banding and spectral
      karyotyping. Fluorescent in situ hybridization analysis indicated that the
      chromosomal breakpoint in band 12p13 was in the sequence from the 5' untranslated
      region to intron 1 of TEL and that the chromosomal breakpoint in band 22q11 was
      in the 3' untranslated region of MN1. The chimeric transcript and protein of MN1
      TEL could not be detected by reverse-transcriptase polymerase chain reaction or
      Western blot analysis. However, the MN1 gene was amplified to three copies
      detected by array comparative genomic hybridization analysis, and the expression
      levels of the MN1 transcript and protein were high in AMU-AML1 cells when
      compared with other cell lines with t(12;22)(p13;q11-12). Our data showed that
      AMU-AML1 cells contain t(12;22)(p13;q11.2) without chimeric fusion of MN1 and
      TEL. The AMU-AML1 cells gained MN1 copies and had high expression levels of MN1.
      Thus, the AMU-AML1 cell line is useful for studying the biological consequences
      of t(12;22)(p13;q11.2) lacking chimeric MN1-TEL.

PMID- 21965129
TI  - Longitudinal predictors of progression of carotid atherosclerosis in rheumatoid
      arthritis.
AB  - OBJECTIVE: To explore predictors of change in measures of carotid atherosclerosis
      among rheumatoid arthritis (RA) patients without known cardiovascular disease
      (CVD) at baseline. METHODS: RA patients underwent carotid ultrasonography at 2
      time points separated by a mean +/- SD of 3.2 +/- 0.3 years. The associations of
      baseline and average patient characteristics with the average yearly change in
      the mean maximal intima-media thickness (IMT) of the common carotid artery (CCA)
      and the internal carotid artery (ICAs) and with incident or progressive plaque in
      the ICA/carotid bulb, were explored. RESULTS: Among the 158 RA patients, the
      maximal CCA-IMT increased in 82% (median 16 MUm/year; P < 0.001) and the maximal
      ICA-IMT increased in 70% (median 25 MUm/year; P < 0.001). Incident plaque was
      observed in 14% of those without plaque at baseline (incidence rate 4.2 per 100
      person-years [95% confidence interval 1.6, 6.8]). Plaque progression was observed
      in 5% of those with plaque at baseline. Among RA predictors, the adjusted average
      yearly change in the maximal CCA-IMT was significantly greater in patients with
      earlier RA than in those with disease of longer duration. Those taking tumor
      necrosis factor (TNF) inhibitors at baseline had a 37% lower adjusted rate of
      progression in the maximal CCA-IMT compared with nonusers (14 MUm/year versus 22
      MUm/year; P = 0.026). For the maximal ICA-IMT, cumulative prednisone exposure was
      associated with progression after adjustment (1.2 MUm/year per gm [95% confidence
      interval 0.1, 2.4]) and was lower in patients who were prescribed statins
      concomitant with prednisone. Higher swollen joint counts and higher average C
      reactive protein levels were both associated with incident or progressive plaque,
      primarily in patients with elevated CVD risk at baseline based on the Framingham
      Risk Score. CONCLUSION: These prospective data provide evidence that inflammation
      is a contributor to the progression of subclinical atherosclerosis in RA and that
      it is potentially modified favorably by TNF inhibitors and detrimentally by
      glucocorticoids.

PMID- 21965130
TI  - Do late adolescent fathers have more depressive symptoms than older fathers?
AB  - Although fathers are increasingly a focus of attention in research, there is a
      dearth of research on depressive symptoms among fathers, especially young fathers
      with toddlers. This study used longitudinal data to examine what risk factors,
      including the age status of fathers (e.g., late adolescence, emerging adulthood,
      and adulthood), may be associated with depressive symptoms of fathers when their
      children were 3 and 5 years of age. A subsample of families for which complete
      data were available on all variables was used in the analyses (n = 1,403). About
      46% of study sample was African American, 27% White, 23% Hispanic, and 4% other
      race/ethnicity. Paternal depressive symptoms were measured using Composite
      International Diagnostic Interview-Short Form (CIDI-SF). Late adolescent
      fatherhood was significantly associated with third-year paternal depressive
      symptoms but not with fifth-year depressive symptoms. Those who reported low
      social support were more likely to be depressed at both times. Fathers who did
      not work for regular pay were more likely to be depressed at the third-year
      follow-up, but not at the fifth-year follow-up. Parenting stress and being
      booked/charged with a crime were not associated with third-year paternal
      depressive symptoms, but were with fifth-year paternal depressive symptoms. This
      study emphasizes the importance of screening for depressive symptoms of fathers
      even before the birth of their child and monitoring and treating postpartum
      depressive symptoms, as first-year depressive symptoms was a significant
      predictor for third- and fifth-year depressive symptoms. Service providers should
      focus on the mental health of fathers as well as mothers to promote healthy
      environments for their children.

PMID- 21965131
TI  - Gender-related risk and protective factors for depressive symptoms and disordered
      eating in adolescence: a 4-year longitudinal study.
AB  - The interplay between intrapersonal risk (low self-esteem, perfectionism and body
      dissatisfaction) and interpersonal protection (social support) appears relevant
      for delineating gender-specific pathways that lead to both depressive and eating
      psychopathology. The aims of this longitudinal study were to examine gender
      differences in the levels of depressive symptoms, disordered eating and the co
      occurrence of both problems from preadolescence to mid-adolescence and to
      identify gender-specific risk and protective factors of depressive symptoms and
      disordered eating. A Spanish community-based sample initially comprising 942
      early adolescents (49% females) was assessed at baseline (T1; X (age) = 10.8
      years) and at 2 and 4-year follow-up (T2 and T3). Gender differences emerged at
      T2 for disordered eating and at T3 for depressive symptoms and for co-occurring
      depressive symptoms and disordered eating. Predictors of depressive symptoms were
      body dissatisfaction, low self-esteem and fear of getting fat, for girls, and
      body dissatisfaction and low self-esteem, for boys. Predictors of disordered
      eating were body dissatisfaction, depressive symptoms, BMI and perfectionism, for
      girls, and low social support and BMI, for boys. In addition, for boys only,
      social support moderated the effect of body dissatisfaction on depressive
      symptoms and the effect of depressive symptoms on disordered eating. The
      hypotheses of the study were partially supported. Clinical implications are
      derived regarding the components that should be included in programs for
      preventing depression and eating disorders in both girls and boys.

PMID- 21965132
TI  - Angiomatoid fibrous histiocytoma on the hard palate: case report.
AB  - BACKGROUND: Angiomatoid fibrous histiocytoma (AFH) is a rare, soft tissue
      sarcoma, which is slow growing with low metastatic potential. We recently had a
      patient present with AFH, which had a palatal perforation and it looked like a
      cyst in the occlusal view. Therefore, the radiological and histological features
      of AFH are reported herein. In addition, the differential diagnosis for this
      lesion is also discussed with a review of the literature. CASE REPORT: A 23-year
      old woman presented with a spontaneous perforation of the palate. Clinically, a
      painless and ulcerative lesion was shown on the mid-palate area. Radiological
      findings revealed a well-demarcated, homogeneous, oval-shaped radiolucent lesion
      in the occlusal view. Histological examination with incisional biopsy, showed a
      relatively well-defined cystic-like mass including tumor cells. Taking into
      consideration the histological and immunohistochemical findings, the presented
      lesion was diagnosed as AFH. Under general anesthesia, the patient underwent a
      modified cylindrical partial maxillectomy including safety margins. DISCUSSION:
      In the present case, clinically differential diagnosis can be made with various
      diseases that have palatal perforations such as trauma, infection, neoplasia,
      collagen vascular disease, and idiopathic conditions. The treatment recommended
      in the literature has been radial excision. The prognosis of the tumor has been
      favorable.

PMID- 21965133
TI  - Biogeographic disjunction between eastern Asia and North America in the Adiantum
      pedatum complex (Pteridaceae).
AB  - PREMISE OF THE STUDY: Biogeographic analyses of ferns with an eastern Asian-North
      American disjunction are few. The Adiantum pedatum complex has such a disjunct
      distribution. The monophyly of the complex needs to be tested and diversification
      history of the four species needs to be reconstructed. METHODS: Plastid (atpA,
      atpB, rbcL, trnL-F, and rps4-trnS) sequences of 100 accessions representing the
      biogeographic diversity of Adiantum were analyzed with parsimony and Bayesian
      inference. Biogeography of the Adiantum pedatum complex was inferred using
      programs DIVA and LAGRANGE. Divergence times of clades were estimated with the
      program BEAST. KEY RESULTS: The A. pedatum complex is monophyletic and sister to
      the eastern Asian A. edentulum. Accessions of A. pedatum do not form a clade;
      instead three subgroups are recognizable. The clade of A. aleuticum and A.
      viridimontanum is nested within A. pedatum. The Asian A. myriosorum is sister to
      the A. pedatum-A. aleuticum clade. Both DIVA and LAGRANGE analyses suggest an
      eastern Asian origin of the A. pedatum complex. The age of the crown A. pedatum
      complex is dated to be at 4.27 (2.24-6.57) million years ago. CONCLUSIONS: The
      currently recognized eastern Asian-North American disjunct species A. pedatum
      needs to be segregated into three species, corresponding to populations in
      eastern North America, China, and Japan. The eastern Asian-North American
      disjunction in the complex is inferred to be the result of two intercontinental
      migrations, one from eastern Asia into North America in the late Tertiary and the
      other from North America back to eastern Asia in the Pleistocene.

PMID- 21965134
TI  - Edge effects on growth and biomass partitioning of an Amazonian understory herb
      (Heliconia acuminata; Heliconiaceae).
AB  - PREMISE: After deforestation, environmental changes in the remaining forest
      fragments are often most intense near the forest edge, but few studies have
      evaluated plant growth or plasticity of plant growth in response to edge effects.
      METHODS: In a 2-year common garden experiment, we compared biomass allocation and
      growth of Heliconia acuminata with identical genotypes grown in 50 * 35 m common
      gardens on a 25-year-old edge and in a forest interior site. KEY RESULTS:
      Genetically identical plants transplanted to the forest edge and understory
      exhibited different patterns of growth and biomass allocation. However,
      individuals with identical genotypes in the same garden often had very different
      responses. Plants on forest edges also had higher growth rates and increased
      biomass at the end of the experiment, almost certainly due to the increased light
      on the forest edge. CONCLUSIONS: With over 70000 km of forest edge created
      annually in the Brazilian Amazon, phenotypic plasticity may play an important
      role in mediating plant responses to these novel environmental conditions.

PMID- 21965135
TI  - Strong phylogenetic effects on floral scent variation of oil-secreting orchids in
      South Africa.
AB  - PREMISE OF THE STUDY: Evolution involves the interplay between natural selection
      and phylogenetic constraint. This is particularly evident among the flowering
      plants where form and diversity of flowers attest to the importance of both
      pollinator-mediated selection and phylogenetic constraint. Although this has been
      studied mostly using visible floral characters, invisible volatile chemicals
      emitted by the flowers should be subject to these same evolutionary forces.
      Unfortunately, most analyses of floral volatiles have over-emphasized the
      importance of natural selection and underplayed phylogenetic constraint without
      quantifying their respective roles in the evolution and composition of floral
      scents. METHODS: We used multivariate analyses to test the relative importance of
      pollinators vs. phylogeny in determining the composition of floral scents among
      oil-secreting orchids in southern Africa. Floral scents of 42 oil-secreting
      taxa/ecotypes distributed among 12 subclades in the tribe Diseae were sampled
      using headspace adsorption and gas chromatography-mass spectroscopy. KEY RESULTS:
      We identified 257 scent compounds distributed over nine different compound
      classes, with the majority of scents dominated by aliphatic or benzenoid
      compounds. The only significant predictor of floral scent among these orchids
      above the species level was phylogeny. Nevertheless, in two of the clades there
      were differences in scent profiles at the species and ecotype level that
      corresponded to different pollinators and were thus suggestive of pollinator
      mediated selection. CONCLUSIONS: Scent variation was greater than expected and
      phylogeny was more important than pollinator-mediated selection in predicting the
      composition of floral scents of oil-secreting orchids, despite the specialized
      nature of the pollinator reward system.

PMID- 21965136
TI  - Complex patterns of autopolyploid evolution in alfalfa and allies (Medicago
      sativa; Leguminosae).
AB  - PREMISE OF THE STUDY: Although there is growing evidence that autopolyploidy is a
      widespread and important evolutionary phenomenon, it has received less attention
      than allopolyploidy. Medicago sativa comprises several diploid and autopolyploid
      taxa, including autotetraploid cultivated alfalfa, and affords an opportunity to
      elucidate the evolutionary history of a morphologically and genetically complex
      autopolyploid system. METHODS: Phylogenies and haplotype networks were
      constructed from two chloroplast noncoding regions (rpl20-rps12 and trnS-trnG
      spacers) across seven diploid and polyploid infraspecific taxa of M. sativa and
      five additional closely related Medicago species, and genetic differentiation was
      estimated. KEY RESULTS: The two most prominent M. sativa autopolyploids have
      contrasting evolutionary histories. Chloroplast data support a simple
      autopolyploid origin of subsp. sativa (alfalfa) from diploid subsp. caerulea,
      from which it is distinguishable in several quantitative characters. In contrast,
      morphologically identical diploid and autopolyploid cytotypes of subsp. falcata
      were found to possess very different chloroplast haplotypes, suggesting past
      introgression from M. prostrata into the polyploid. Despite the presence of
      hybrids between tetraploid subspecies falcata and sativa, there was little
      evidence of introgression of chloroplast genomes from either subspecies into the
      other. CONCLUSIONS: Autopolyploid evolution in M. sativa is complicated and has
      followed very different paths in different subspecific taxa. The potential exists
      for gene flow in virtually all combinations of subspecies both within and between
      ploidies, yet despite the existence of hybrids, morphologically and genetically
      distinctive subspecies persist.

PMID- 21965137
TI  - Intermolt development reduces oxygen delivery capacity and jumping performance in
      the American locust (Schistocerca americana).
AB  - Among animals, insects have the highest mass-specific metabolic rates; yet,
      during intermolt development the tracheal respiratory system cannot meet the
      increased oxygen demand of older stage insects. Using locomotory performance
      indices, whole body respirometry, and X-ray imaging to visualize the respiratory
      system, we tested the hypothesis that due to the rigid exoskeleton, an increase
      in body mass during the intermolt period compresses the air-filled tracheal
      system, thereby, reducing oxygen delivery capacity in late stage insects.
      Specifically, we measured air sac ventilation frequency, size, and
      compressibility in both the abdomen and femur of early, middle, and late stage
      sixth instar Schistocerca americana grasshoppers. Our results show that late
      stage grasshoppers have a reduced air sac ventilation frequency in the femur and
      decreased convective capacities in the abdomen and femur. We also used X-ray
      images of the abdomen and femur to calculate the total proportion of tissue
      dedicated to respiratory structure during the intermolt period. We found that
      late stage grasshoppers had a lower proportion of their body dedicated to
      respiratory structures, especially air sacs, which convectively ventilate the
      tracheal system. These intermolt changes make oxygen delivery more challenging to
      the tissues, especially critical ones such as the jumping muscle. Indeed, late
      stage grasshoppers showed reduced jump frequencies compared to early stage
      grasshoppers, as well as decreased mass-specific CO(2) emission rates at 3 kPa
      PO(2). Our findings provide a mechanism to explain how body mass changes during
      the intermolt period reduce oxygen delivery capacity and alter an insect's life
      history.

PMID- 21965138
TI  - Pooling systematic reviews of systematic reviews: a Bayesian panoramic meta
      analysis.
AB  - Systematic reviews and meta-analyses usually synthesise evidence from studies
      reporting outcomes from particular interventions in specific diseases. For
      example, a meta-analysis of prophylactic antibiotics (intervention) in elective
      arterial reconstruction (disease) for rates of wound infection (outcome).
      However, because systematic reviews and meta-analyses are so widespread, a body
      of evidence often exists around specific intervention effects on particular
      outcomes over a range of diseases. So for example, a multitude of independent
      meta-analyses have evaluated rates of wound infection with and without the use of
      prophylactic antibiotics over multiple surgery types. A systematic review of
      systematic reviews is a means of synthesising evidence for the same intervention
      over multiple disease types. We propose a panoramic meta-analysis as a means of
      pooling effect estimates over systematic reviews of systematic reviews. We
      explore several methods ranging from a simple two-step approach, to a meta
      regression or mixed effects approach, where variation between diseases are
      modelled as fixed covariate effects and between-study variation by random
      effects, and to a three-level hierarchical model in which exchangeability is
      assumed, which allows both a between-disease component of variance and a between
      study (within disease) component of variance. In the surgery example, we pool 18
      meta-analyses (each including between 4 and 26 studies) of prophylactic
      antibiotics reporting rates of wound infection from 18 different surgery sites to
      obtain a single pooled estimate of effect and estimates of between-disease,
      within-disease and within-study variability.

PMID- 21965139
TI  - Hepatocellular carcinoma presenting with multiple bone and soft tissue metastases
      and atypical cytomorphological features--a rare case report.
AB  - Hepatocellular carcinoma (HCC) with atypical cytomorphological features and
      presenting with bone and soft tissue metastasis is very rare. We report a 65-year
      old male patient of HCC who presented with bone and soft tissue metastases and
      was clinically and radiologically suspected to have a soft tissue sarcoma. The
      patient presented with severe cervical pain with palpable masses in right
      scapular, nape of neck, and occiput area of scalp. Radiologically, these were
      large, bulky soft tissue masses expansile, destructive, and lytic in nature.
      Cytomorphologic studies revealed HCC with uncommon features of multinucleated
      osteoclast-like giant cell and very prominent intracytoplasmic hyaline bodies
      (IHBs). Cytology, immunohistochemistry on cell block preparation, rising serum
      alpha-fetoprotein (AFP) levels (1121.93-5000 ng/ml), and PIVKA II levels
      confirmed the diagnosis. The patient has been on follow-up on sorafinib for 2
      months and is doing well. This case emphasizes the need for systematic approach
      in cases of HCC with atypical clinical presentation and unusual cytomorphology.

PMID- 21965140
TI  - Gamma-secretase inhibitor enhances the cytotoxic effect of bortezomib in multiple
      myeloma.
AB  - BACKGROUND: Targeting of Notch signaling with gamma-secretase inhibitors (GSIs)
      has been considered a promising strategy for the treatment of hematological
      malignancies including multiple myeloma (MM). Here we investigated whether the
      cytotoxic effect of bortezomib, an agent commonly used in MM, could be enhanced
      by the addition of a GSI. METHODS: MM cells were treated with GSI, bortezomib or
      the combination thereof. Apoptosis of MM cells, proteasome activity and Notch
      signaling activation were determined. The effect of the drug combination was also
      evaluated in MM cells transfected with the active domain of Notch-1. RESULTS:
      Using MM cell lines and primary MM cells isolated from the bone marrow of
      patients with MM we found a strong synergistic effect of bortezomib in
      combination with one of the GSIs studied. We next investigated the mechanism
      underlying this synergistic effect and determined that the effect of the drug
      combination was mainly dependent on the ability of the selected GSI to inhibit
      proteasome activity in MM cells. CONCLUSION: Our study demonstrates that selected
      GSIs that inhibit proteasome activity may be successfully used in combination
      with bortezomib enhancing its anti-MM effect.

PMID- 21965141
TI  - Revisit of multiple epiphyseal dysplasia: ethnic difference in genotypes and
      comparison of radiographic features linked to the COMP and MATN3 genes.
AB  - Multiple epiphyseal dysplasia (MED) is a genetically heterogeneous group of
      diseases characterized by variable degrees of epiphyseal abnormality primarily
      involving the hip and knee joints. The purpose of this study was to investigate
      the frequency of mutations in individuals with a clinical and radiographic
      diagnosis of MED and to test the hypothesis that characteristic radiological
      findings may be helpful in predicting the gene responsible. The radiographs of 74
      Korean patients were evaluated by a panel of skeletal dysplasia experts. Six
      genes known to be associated with MED (COMP, MATN3, COL9A1, COL9A2, COL9A3, and
      DTDST) were screened by sequencing. Mutations were found in 55 of the 63 patients
      (87%). MATN3 mutations were found in 30 patients (55%), followed by COMP
      mutations in 23 (41%), and COL9A2 and DTDST mutations in one patient (2%) each.
      Comparisons of radiographic findings in patients with COMP and MATN3 mutations
      showed that albeit marked abnormalities in hip and knee joints were observed in
      both groups, the degree of involvement and the morphology of dysplastic epiphyses
      differed markedly. The contour of the pelvic acetabulum, the presence of
      metaphyseal vertical striations, and/or the brachydactyly of the hand were also
      found to be highly correlated with the genotypes. The study confirms that MATN3
      and COMP are the genes most frequently responsible for MED and that subtle
      radiographic signs may give precious indications on which gene(s) should be
      prioritized for mutational screening in a given individual.

PMID- 21965142
TI  - Commentary: Do we have a consistent terminology for species diversity? Back to
      basics and toward a unifying framework.
AB  - After decades of misusing the term diversity in community ecology, over the last
      5 years some papers have offered important advances toward developing a more
      rigorous mathematical background, which allows us to achieve more clarity in the
      terminology for the vast range of biological phenomena that have been placed
      under the umbrella of this term. Some points have been clearly stated in previous
      papers of this Views and Comments section, and new terms have even been proposed
      for specific cases, but other issues, such as the need for the prefix true have
      not been discussed. Our aim is to clarify some of the terms and concepts, the
      proper use of which appears still to remain unclear, and to provide biologists
      with a simplified version of the general framework resulting from recent
      contributions, with an emphasis on identifying points of consensus in the field.
      We also comment on the possibility of extending the basics of this general
      framework to other facets of the broad term biodiversity, such as functional or
      phylogenetic diversity.

PMID- 21965143
TI  - Bilateral dysplasia epiphysealis hemimelica of the talus associated with a lower
      leg intramuscular cartilaginous mass.
AB  - Dysplasia epiphysealis hemimelica (DEH), or Trevor disease, is a rare skeletal
      dysplasia characterised by an osteocartilaginous mass arising from an epiphysis.
      It affects single or multiple epiphyses in children, usually in the lower limb,
      predominantly the knee and ankle. Bilateral involvement is extremely rare, with
      only four cases reported in the literature to date. We report an additional case
      of bilateral DEH of the talus in a 14-year-old girl with an associated, not
      previously reported, intramuscular cartilaginous mass of the left lower leg.
      Clinical, radiological and pathological findings are presented. We emphasise the
      role of MRI and US in the diagnosis of DEH.

PMID- 21965144
TI  - Embryonic staging table for a direct-developing salamander, Plethodon cinereus
      (Plethodontidae).
AB  - This work presents a refined staging table for the direct-developing red-backed
      salamander Plethodon cinereus, which is based on the incomplete staging system of
      James Norman Dent (J Morphol 1942; 71:577-601). This common species from eastern
      North America is a member of the species-rich lungless salamander family
      Plethodontidae. The staging table presented here covers several stages omitted by
      Dent and reveals novel developmental features of P. cinereus embryos. These
      include putative Leydig cells and open gill clefts, which are found in larvae of
      metamorphosing species but were previously reported as absent in direct
      developing Plethodon. Other features found in larvae of metamorphosing salamander
      species, such as the palatopterygoid bone and lateral line neuromasts, were not
      observed in this material. The occurrence of larval and metamorphic features in
      these embryos has direct bearing on the patterns of life history evolution within
      the plethodontidae family. This study emphasizes the degree to which typically
      larval structures are retained in this direct-developing species and provides a
      staging table for further investigations into the development and evolution of
      plethodontid salamanders.

PMID- 21965145
TI  - Copy number alterations in prostate tumors and disease aggressiveness.
AB  - Detecting genomic alterations that result in more aggressive prostate cancer may
      improve clinical treatment and our understanding of the biology underlying this
      common but complex disease. To this end, we undertook a genome-wide copy number
      alterations (CNAs) study of clinicopathological characteristics of 62 prostate
      tumors using the Illumina 1M single nucleotide polymorphism array. The highest
      overall frequencies of CNAs were on chromosomes 8q (gains), 8p (loss and copy
      neutral), and 6q (copy-loss). Combined loss and copy-neutral events were
      associated with increasing disease grade (P = 0.03), stage (P = 0.01), and
      diagnostic prostate specific antigen (PSA) (P = 0.01). Further evaluation of CNAs
      using gene ontology identified pathways involved with disease aggressiveness. The
      "regulation of apoptosis" pathway was associated with stage of disease (P =
      0.004), while the "reproductive cellular process" pathway was associated with
      diagnostic PSA (P = 0.00038). Specific genes within these pathways exhibited
      strong associations with clinical characteristics; for example, in the apoptosis
      pathway BNIP3L was associated with increasing prostate tumor stage (P = 0.007).
      These findings confirm known regions of CNAs in prostate cancer and localize
      additional regions and possible genes (e.g., BNIP3L, WWOX, and GATM) that may
      help to clarify the genetic basis of prostate cancer aggressiveness.

PMID- 21965146
TI  - Culture temperature modulates aggregation of recombinant antibody in cho cells.
AB  - During production of therapeutic monoclonal antibodies (mAb), it is highly
      desirable to remove and control antibody aggregates in the manufacturing process
      to minimize the potential risk of immunogenicity to patients. During process
      development for the production of a recombinant IgG in a CHO cell line, we
      observed atypical high variability from 1 to 20% mAb aggregates formed during
      cell culture that negatively impacted antibody purification. Analytical
      characterization revealed the IgG aggregates were mediated by hydrophobic
      interactions likely caused by misfolded antibody during intracellular processing.
      Strikingly, data analysis showed an inverse correlation of lower cell culture
      temperature producing higher aggregate levels. All cultures at 37 degrees C
      exhibited <= 5% aggregates at harvest. Aggregate levels increased 4-12-fold in 33
      degrees C cultures when compared to 37 degrees C, with a corresponding 2-4-fold
      increase in heavy chain (HC) and light chain (LC) mRNA. Additionally, 37 degrees
      C cases showed a greater excess of LC to HC mRNA levels. Endoplasmic reticulum
      (ER) chaperone expression and ER size also increased 25-75% at 33 degrees C
      versus 37 degrees C but to a lesser extent than LC and HC mRNA, consistent with a
      potential limiting ER folding capacity at 33 degrees C for this cell line.
      Finally, we identified a 2-5-fold increase in mAb aggregate formation at 33
      degrees C compared to 37 degrees C cultures for three additional CHO cell lines.
      Taken together, our observations indicate that low culture temperature can
      increase antibody aggregate formation in CHO cells by increasing LC and HC
      transcripts coupled with limited ER machinery.

PMID- 21965148
TI  - Fine needle aspiration cytology of epithelioid hemangioendothelioma of soft
      tissue.

PMID- 21965149
TI  - Short-term cancer mortality projections: a comparative study of prediction
      methods.
AB  - This paper provides a systematic comparison of cancer mortality and incidence
      projection methods used at major national health agencies. These methods include
      Poisson regression using an age-period-cohort model as well as a simple log
      linear trend, a joinpoint technique, which accounts for sharp changes,
      autoregressive time series and state-space models. We assess and compare the
      reliability of these projection methods by using Canadian cancer mortality data
      for 12 cancer sites at both the national and regional levels. Cancer sites were
      chosen to provide a wide range of mortality frequencies. We explore specific
      techniques for small case counts and for overall national-level projections based
      on regional-level data. No single method is omnibus in terms of superior
      performance across a wide range of cancer sites and for all sizes of populations.
      However, the procedures based on age-period-cohort models used by the Association
      of the Nordic Cancer Registries tend to provide better performance than the other
      methods considered. The exception is when case counts are small, where the
      average of the observed counts over the recent 5-year period yields better
      predictions.

PMID- 21965147
TI  - New mutations in the ATM gene and clinical data of 25 AT patients.
AB  - Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by
      cerebellar degeneration, immunodeficiency, oculocutaneous telangiectasias,
      chromosomal instability, radiosensitivity, and cancer predisposition. The gene
      mutated in the patients, ATM, encodes a member of the phosphatidylinositol 3
      kinase family proteins. The ATM protein has a key role in the cellular response
      to DNA damage. Truncating and splice site mutations in ATM have been found in
      most patients with the classical AT phenotype. Here we report of our extensive
      ATM mutation screening on 25 AT patients from 19 families of different ethnic
      origin. Previously unknown mutations were identified in six patients including a
      new homozygous missense mutation, c.8110T>C (p.Cys2704Arg), in a severely
      affected patient. Comprehensive clinical data are presented for all patients
      described here along with data on ATM function generated by analysis of cell
      lines established from a subset of the patients.

PMID- 21965150
TI  - Surgical treatment of pediatric trigeminal neuralgia: case series and review of
      the literature.
AB  - PURPOSE: Pediatric trigeminal neuralgia (TN) is a rare entity. The purpose of
      this study was to retrospectively analyze a small series of pediatric patients
      diagnosed with TN and surgically treated with microvascular decompression (MVD)
      at a single center. METHODS: Nine patients were identified who presented with TN
      symptoms that began before the age of 18. Four were excluded because of delayed
      surgical intervention or successful medical management. We retrospectively
      reviewed the charts of 5 patients with classical TN who underwent MVD at or
      before the age of 18. RESULTS: Patient ages ranged from 3 to 18 years (average,
      11.7) at the time of procedure. All five patients were female. Four patients
      underwent a single procedure and one had bilateral MVDs. In all six cases,
      vascular compression of the trigeminal nerve was found during surgery.
      Compression was venous in three cases, arterial in two, and both in one. Pain
      relief was complete following the procedure in five of six cases. Pain relief was
      incomplete but substantial in one patient, allowing her to discontinue
      anticonvulsant medications. Follow-up duration ranges from 9.1 to 24.8 months
      with an average of 15.3 (+/- 6.1) and a median of 12.7 months follow-up. There
      were no complications such as CSF leak, infection, or cranial nerve deficits.
      CONCLUSIONS: Until now, there had been no reports on the effectiveness of MVD
      performed before the age of 18 to treat TN. These preliminary results suggest MVD
      may be performed with good pain relief and minimal side effects in the pediatric
      population.

PMID- 21965151
TI  - Giant pericardial thrombus and cardiac tamponade.

PMID- 21965152
TI  - Two-dimensional myocardial strain imaging detects changes in left ventricular
      systolic function immediately after anthracycline chemotherapy.
AB  - AIMS: The efficacy of anthracyclines is undermined by potential life-threatening
      cardiotoxicity. Cardiotoxicity is dependent upon several factors and the timing
      to its development is variable. Moreover, as adjuvant therapy with trastuzumab
      often follows, a close monitoring of cardiac function in those treated with
      anthracyclines is mandatory. Left ventricular ejection fraction (LVEF) by
      echocardiography is currently used for monitoring cardiotoxicity; however, LVEF
      has numerous limitations. Two-dimensional strain imaging may provide a more
      sensitive measure of altered LV systolic function, so the aim of the present
      study was to compare LVEF and LV systolic strain before and after anthracyclines.
      METHODS AND RESULTS: Fifty-two women with histologically confirmed breast cancer
      were prospectively studied. Echocardiographic LVEF (by Simpson's method), global
      and regional peak longitudinal, radial, and circumferential 2D systolic strain
      were measured 1 week before and 1 week after chemotherapy. Global and regional
      longitudinal LV systolic strain was significantly reduced after treatment; global
      longitudinal strain decreased from -17.7 to -16.3% (P < 0.01) with 48% of global
      measurements reduced by >10%. Global and regional radial LV systolic strain after
      treatment was also significantly reduced; global radial strain dropped from 40.5
      to 34.5% (P < 0.01) with 59% of global measurements reduced by >10%. In contrast,
      no reduction in LVEF >10% after chemotherapy was observed. CONCLUSION: Reduced LV
      systolic strain immediately after anthracycline treatment may indicate early
      impairment of myocardial function before detectable change in LVEF.

PMID- 21965153
TI  - Relationship of contrast-enhanced magnetic resonance imaging-derived intramural
      scar distribution and speckle tracking echocardiography-derived left ventricular
      two-dimensional strains.
AB  - AIMS: Information is limited regarding the functional correlates of intramural
      scar burden in myopathic hearts. We aimed to explore the use of speckle tracking
      echocardiography selectively at three intramural locations, to investigate the
      variance in cardiac strains and their relationship to contrast-enhanced magnetic
      resonance imaging-derived scar distribution and global left ventricular systolic
      function. METHODS AND RESULTS: Fifty-nine patients with evidence of myocardial
      fibrosis on contrast-enhanced magnetic resonance imaging and 18 healthy subjects
      underwent speckle tracking echocardiography for measuring subendocardial,
      midmyocardial, and subepicardial strains in longitudinal, circumferential, and
      radial directions. Patients were divided into three categories of scar
      distribution: Group A, endocardial and midmyocardial; Group B, midmyocardial and
      epicardial; and Group C, transmural. When these patients were compared with 18
      healthy control subjects, longitudinal left ventricular deformation was
      attenuated equally for all three groups, whereas circumferential strain was
      relatively well preserved. On multivariate analysis, circumferential strain and
      scar burden were independent determinants of left ventricular ejection fraction
      (R(2) = 0.57; P = 0.003 for strain burden and P = 0.01 for scar burden).
      CONCLUSION: Longitudinal strains are attenuated independent of myocardial scar
      location. This alteration in left ventricular deformation is associated with
      circumferential mechanics becoming a key determinant of global left ventricular
      pump function in myopathic hearts.

PMID- 21965154
TI  - Localized hematoma: the importance of careful echocardiographic assessment.

PMID- 21965155
TI  - Congenital diaphragmatic hernia in Smith-Magenis syndrome: a possible locus at
      chromosome 17p11.2.
AB  - We report on a 7-month-old girl with Smith-Magenis syndrome (SMS) due to a 4.76
      Mb deletion of 17p12-17p11.2 detected by array comparative genomic hybridization.
      She was also affected with a left-sided congenital diaphragmatic hernia (CDH) and
      cardiac anomalies including an atypical atrioventricular canal defect and a cleft
      mitral valve. To our knowledge, this is the first reported case of a patient with
      both SMS and CDH. There are numerous chromosomal regions in which duplications,
      deletions, inversions, or translocations have been associated with CDH, but none
      have previously been reported at or close to 17p11.2. We discuss candidate genes
      for the diaphragmatic defect in this patient. Our case demonstrates that it is
      important to consider the possibility of SMS in non-isolated cases of
      diaphragmatic hernia.

PMID- 21965156
TI  - Assessment of the fecal lactobacilli population in patients with hepatitis B
      virus-related decompensated cirrhosis and hepatitis B cirrhosis treated with
      liver transplant.
AB  - This study aims to provide an overview of the diversity of intestinal
      Lactobacillus among Chinese patients with hepatitis B virus (HBV)-related
      decompensated cirrhosis and who received liver transplant for hepatitis B
      cirrhosis. Fecal samples were collected from 38 healthy volunteers, 61 patients
      with HBV-related decompensated cirrhosis (group LC) and 74 patients who had liver
      transplant for hepatitis B cirrhosis (group LT). Quantitative polymerase chain
      reaction technology with species-specific primers was applied to investigate
      lactobacilli 16S rDNA in crude DNA, extracted from fecal samples. Software
      package Statistical Package for the Social Sciences and Palaeontological
      Statistics for Windows was used to analyze the data. Lactobacilli population of
      the two patient groups was different from the healthy control subjects, principal
      differences being marked decrease in the population of Lactobacillus rhamnosus (p
      < 0.001 for both patient groups) and reduction in the frequency of Lactobacillus
      fermentus (p < 0.001 for group LC and p < 0.01 for group LT). Our findings on the
      frequency of lactobacilli population suggested decreased diversity in groups LC
      and LT (compared with the healthy controls (p < 0.001 and p < 0.01,
      respectively)). Patients tended to have less complex fecal lactobacilli
      composition than the healthy controls, especially in the group LC.

PMID- 21965157
TI  - Estrogen and insulin replacement therapy modulates the expression of insulin-like
      growth factor-I receptors in the salivary glands of diabetic mice.
AB  - Diabetes mellitus results in various complications, also compromising the
      salivary glands. Hormone levels and interactions with cellular receptors are
      altered, intensifying the damage caused by this disease. Hormone replacement
      therapy alone or combined with other treatments may reverse this damage, but
      doubts still exist regarding the efficacy of this procedure. The objective of
      this study was to evaluate the effect of estrogen replacement therapy combined
      with insulin treatment on salivary secretory cells and on the expression of
      insulin-like growth factor (IGF)-I receptors in salivary glands of spontaneously
      diabetic (NOD) mice. Twenty-five mice were divided into five groups of five
      animals each: group I (NOD diabetic), group II (NOD diabetic treated with
      insulin), group III (NOD diabetic treated with estrogen), group IV (NOD diabetic
      treated with insulin and estrogen), and group V (control Balb/c mice). Group II
      received insulin, group III received estrogen, and group IV received insulin plus
      estrogen administered daily for 20 days. Groups I and V received saline for the
      same period of time to simulate treatment. Glucose and estrogen levels were
      monitored during treatment, and salivary gland samples were collected at the end
      of treatment for stereological analysis and immunofluorescence detection of IGF-I
      receptors. Tissue restructuring and regulation of IGF-I receptors expression were
      observed in animals submitted to estrogen replacement therapy plus insulin.
      Estrogen effectively promoted the recovery of salivary secretory cells,
      demonstrating that this hormone alone, and especially when combined with insulin,
      might be important for the reversal of hyperglycemia-induced tissue injury.

PMID- 21965158
TI  - Guideline, education, and peer comparison to reduce prescriptions of
      benzodiazepines and low-dose quetiapine in prison.
AB  - Benzodiazepines (antianxiety medications) and quetiapine (an antipsychotic
      medication) are subject to abuse in prison. Quetiapine is also expensive and has
      serious side effects. The prescription of these medications in prison for anxiety
      and insomnia is not the preferred choice. In order to reduce these prescriptions,
      the University of Medicine and Dentistry of New Jersey-University Correctional
      HealthCare (UCHC), working within the New Jersey Department of Corrections,
      provided its psychiatrists with a guideline to the treatment of insomnia in
      prison. The guideline discouraged pharmacological treatment of insomnia. UCHC
      then anonymously compared the prescribing practices of its psychiatrists to each
      other, and educated the psychiatrists about the disadvantages of benzodiazepines
      and low-dose quetiapine in prison. These techniques reduced the numbers of
      inmates prescribed benzodiazepines by 38% after 20 months and reduced the numbers
      of inmates prescribed low-dose quetiapine by 59% after 22 months.

PMID- 21965159
TI  - Performance of a fully automatic lesion detection system for breast DCE-MRI.
AB  - PURPOSE: To describe and test a new fully automatic lesion detection system for
      breast DCE-MRI. MATERIALS AND METHODS: Studies were collected from two
      institutions adopting different DCE-MRI sequences, one with and the other one
      without fat-saturation. The detection pipeline consists of (i) breast
      segmentation, to identify breast size and location; (ii) registration, to correct
      for patient movements; (iii) lesion detection, to extract contrast-enhanced
      regions using a new normalization technique based on the contrast-uptake of
      mammary vessels; (iv) false positive (FP) reduction, to exclude contrast-enhanced
      regions other than lesions. Detection rate (number of system-detected malignant
      and benign lesions over the total number of lesions) and sensitivity (system
      detected malignant lesions over the total number of malignant lesions) were
      assessed. The number of FPs was also assessed. RESULTS: Forty-eight studies with
      12 benign and 53 malignant lesions were evaluated. Median lesion diameter was 6
      mm (range, 5-15 mm) for benign and 26 mm (range, 5-75 mm) for malignant lesions.
      Detection rate was 58/65 (89%; 95% confidence interval [CI] 79%-95%) and
      sensitivity was 52/53 (98%; 95% CI 90%-99%). Mammary median FPs per breast was 4
      (1st-3rd quartiles 3-7.25). CONCLUSION: The system showed promising results on MR
      datasets obtained from different scanners producing fat-sat or non-fat-sat images
      with variable temporal and spatial resolution and could potentially be used for
      early diagnosis and staging of breast cancer to reduce reading time and to
      improve lesion detection. Further evaluation is needed before it may be used in
      clinical practice.

PMID- 21965160
TI  - Batch, fed-batch, and microcarrier cultures with CHO cell lines in a pressure
      cycle driven miniaturized bioreactor.
AB  - Miniaturized bioreactors for suspension cultures of animal cells, such as Chinese
      Hamster Ovary (CHO) cells, could improve bioprocess development through the
      ability to cheaply explore a wide range of bioprocess operating conditions. A
      miniaturized pressure-cycled bioreactor for animal cell cultures, described
      previously (Diao et al., 2008), was tested with a suspension CHO cell line
      producing commercially relevant quantities of human IgG. Results from the
      suspended CHO cell line showed that the cell growth was comparable to
      conventional flask controls and the target protein production was enhanced in the
      minibioreactor, which may be due to the relatively high oxygen transfer rate and
      the moderate shear stress, measured and simulated previously. Microcarrier
      culture using an anchorage-dependent CHO cell line and Cytodex 3 also showed a
      similar result: comparable growth and enhanced production of a model protein
      (secreted alkaline phosphatase or SEAP). Various fed-batch schemes were applied
      to the CHO cells producing human IgG, yielding cell numbers (1.1 * 10(7) /mL) at
      day 8 and titers of human IgG (2.3 g/L) at day 14 that are typical industrial
      values for CHO cell fed-batch cultures. The alteration of the volumetric oxygen
      transfer coefficient is a key parameter for viability of the CHO cell line
      producing human IgG. We conclude that the minibioreactor can provide favorable
      cell culture environments; oxygen transfer coefficient and mixing time can be
      altered to mimic values in a larger scale system allowing for potential
      prediction of response during scale-up.

PMID- 21965161
TI  - Let the pigeon drive the bus: pigeons can plan future routes in a room.
AB  - The task of determining an optimal route to several locations is called the
      traveling salesperson problem (TSP). The TSP has been used recently to examine
      spatial cognition in humans and non-human animals. It remains unclear whether or
      not the decision process of animals other than non-human primates utilizes rigid
      rule-based heuristics, or whether non-human animals are able to flexibly 'plan'
      future routes/behavior based on their knowledge of multiple locations. We
      presented pigeons in a One-way and Round-Trip group with TSPs that included two
      or three destinations (feeders) in a laboratory environment. The pigeons departed
      a start location, traveled to each feeder once before returning to a final
      destination. Pigeons weighed the proximity of the next location heavily, but
      appeared to plan ahead multiple steps when the travel costs for inefficient
      behavior appeared to increase. The results provide clear and strong evidence that
      animals other than primates are capable of planning sophisticated travel routes.

PMID- 21965162
TI  - Sunitinib-induced nephrotic syndrome in association with drug response in a
      patient with Xp11.2 translocation renal cell carcinoma.
AB  - We report the case of a patient with metastatic renal cell carcinoma with Xp11.2
      translocation/transcription factor E3 (TFE3) gene fusion who had presented with
      sunitinib-induced nephrotic syndrome in association with favorable and durable
      treatment response. The nephrotic syndrome was managed successfully by
      discontinuing sunitinib and symptomatic treatment. The 27-year-old female patient
      presenting with right upper abdominal pain was diagnosed with Xp11.2
      translocation renal cell carcinoma on the right side with multiple pulmonary and
      hepatic metastases. She underwent radical nephrectomy and took a daily dose of
      37.5 mg sunitinib. Partial response to sunitinib was achieved and maintained for
      5 months, but when nephrotic syndrome occurred, drug intake was discontinued. The
      nephrotic syndrome gradually resolved around 2 months after discontinuation of
      sunitinib and medical management. Our case highlighted the favorable response of
      a particular non-clear cell type renal cell carcinoma to sunitinib and the
      specific toxicity associated with the antiangiogenic effect of sunitinib.

PMID- 21965163
TI  - Clinical outcome and prognostic factors of sorafenib in Japanese patients with
      advanced renal cell carcinoma in general clinical practice.
AB  - OBJECTIVE: Effects of sorafenib in general clinical practice, especially those
      with patients of Asian ethnicity, have been rarely investigated. We assessed
      efficacy, safety and prognostic factors for progression-free survival in Japanese
      patients receiving sorafenib for advanced renal cell carcinoma. METHODS: We
      performed a retrospective analysis of 159 Japanese patients with renal cell
      carcinoma. Progression-free survival was estimated by the Kaplan-Meier method.
      Objective response (per Response Evaluation Criteria in Solid Tumors) and safety
      were assessed. Cox proportional hazards model was used to identify independent
      prognostic factors for progression-free survival. RESULTS: The median progression
      free survival was 9.0 months (95% confidence interval, 7.5-10.6 months). In 142
      patients with measurable lesions, the objective response rate was 21.8%, and
      disease control was achieved in 85 (59.9%) patients. Adverse events of any grade
      occurred in 152 patients (95.6%). Most common adverse events causing
      discontinuation or interruption of sorafenib were hand-foot skin reaction (22%),
      rash (10.7%) and liver dysfunction (10.7%). Dose reduction or therapy
      interruption due to adverse events was required in 128 patients (80.5%).
      Univariate and multivariate analysis revealed that favorable prognosis according
      to Memorial Sloan-Kettering Cancer Center prognostic factors and relative dose
      intensity during the first month of treatment of >=50% were significant factors
      for predicting superior progression-free survival with sorafenib treatment.
      CONCLUSIONS: Sorafenib was effective in Japanese patients with advanced renal
      cell carcinoma in general clinical practice and was tolerated although most
      patients required dose reduction or interruption of therapy. Future studies
      should establish new strategies for treatment without sacrificing both efficacy
      and patient quality of life.

PMID- 21965164
TI  - Clinical practice in management of hydration for lung cancer patients receiving
      cisplatin-based chemotherapy in Japan: a questionnaire survey.
AB  - A questionnaire survey was performed to investigate the actual hydration methods
      used with cisplatin-containing regimens at various institutions in Japan to gain
      an overview of the varieties employed. Replies were received from 368 of 686
      institutions board-certified by the Japanese Respiratory Society. In 233
      institutions (63%), new lung cancer patients were treated regularly with regimens
      containing cisplatin at >=60 mg/m2. In 172 institutions (48%), hydration with
      <3000 ml of intravenous saline was performed on day 1. In 225 institutions (65%),
      hydration was performed for up to 3 days at most, but no more than 48 (14%) of
      the institutions that responded did so on day 1 only. Two to three weeks of
      hospitalization was needed for the initial course at most institutions (76%).
      Thirteen institutions (4%) treated patients as outpatients after the second
      course, whereas none did so from the beginning of treatment. Despite
      inconsistencies among the methods used by the various institutions, 84% of those
      surveyed considered their approaches to be appropriate. Some useful objective
      indices for deciding the volume or duration of hydration are needed.

PMID- 21965165
TI  - Reweighting estimators for Cox regression with missing covariate data: analysis
      of insulin resistance and risk of stroke in the Northern Manhattan Study.
AB  - Incomplete covariates often obscure analysis results from a Cox regression. In an
      analysis of the Northern Manhattan Study (NOMAS) to determine the influence of
      insulin resistance on the incidence of stroke in nondiabetic individuals, insulin
      level is unknown for 34.1% of the subjects. The available data suggest that the
      missingness mechanism depends on outcome variables, which may generate biases in
      estimating the parameters of interest if only using the complete observations.
      This article aimed to introduce practical strategies to analyze the NOMAS data
      and present sensitivity analyses by using the reweighting method in standard
      statistical packages. When the data set structure is in counting process style,
      the reweighting estimates can be obtained by built-in procedures with variance
      estimated by the jackknife method. Simulation results indicate that the jackknife
      variance estimate provides reasonable coverage probability in moderate sample
      sizes. We subsequently conducted sensitivity analyses for the NOMAS data, showing
      that the risk estimates are robust to a variety of missingness mechanisms. At the
      end of this article, we present the core SAS and R programs used in the analysis.

PMID- 21965166
TI  - Immunohistochemical analysis of the proteolytic enzyme subtilase in the digestive
      organs of the sea urchin Strongylocentrotus intermedius.
AB  - Subtilase, a major protease in the short-spined sea urchin (Strongylocentrotus
      intermedius), was isolated and used as antigen for the subsequent production of a
      specific polyclonal antibody. Immunoreactive cells were observed by
      immunohistochemical analysis in granules in the anterior and posterior stomach
      and the anterior intestine. These granules, which were most numerous in the
      anterior stomach, also stained intensely with methylene blue-Azure II. However,
      granules in cells of the esophagus, posterior intestine, and rectum were not
      stained by this antibody. We conclude that subtilase mainly localizes in the
      stomach and anterior intestine of the sea urchin.

PMID- 21965167
TI  - Common structural features characterize interstitial intrachromosomal Xp and 18q
      triplications.
AB  - Rare intrachromosomal triplications producing partial tetrasomies have been
      reported for a number of chromosomes. A detailed molecular characterization,
      necessary to define the mechanism of their formation, has so far been lacking. We
      report on the detailed clinical, cytogenetic, and molecular characterization of
      two triplications, one de novo involving chromosome 18q, the other familial on
      chromosome Xp. The clinical phenotype of the patient with 18q triplication, very
      likely due to overexpression of one or more of the genes in the region, consists
      mainly of facial dysmorphisms and developmental delay. The familial Xp
      triplication does not cause an increase in the number of copies of any gene and
      is almost certainly a polymorphism. The rearrangements are actually complex
      duplications/triplications. In both patients, their proximal breakpoints are
      located within complex segmental duplications, one containing the VCX gene
      cluster on chromosome Xp, the other the TCEB3 genes on chromosome 18q. A proximal
      duplicated region is also present in both patients. All junctions we analyzed
      were formed by non-homologous end joining (NHEJ). The structural features shared
      between our patients suggest the involvement of a common mechanism in the genesis
      of interstitial intrachromosomal triplications.

PMID- 21965168
TI  - In vivo MR quantification of superparamagnetic iron oxide nanoparticle leakage
      during low-frequency-ultrasound-induced blood-brain barrier opening in swine.
AB  - PURPOSE: To verify that low-frequency planar ultrasound can be used to disrupt
      the BBB in large animals, and the usefulness of MRI to quantitatively monitor the
      delivery of superparamagnetic iron oxide (SPIO) nanoparticles into the disrupted
      regions. MATERIALS AND METHODS: Two groups of swine subjected to craniotomy were
      sonicated with burst lengths of 30 or 100 ms, and one group of experiment was
      also performed to confirm the ability of 28-kHz sonication to open the BBB
      transcranially. SPIO nanoparticles were administered to the animals after BBB
      disruption. Procedures were monitored by MRI; SPIO concentrations were estimated
      by relaxivity mapping. RESULTS: Sonication for 30 ms created shallow disruptions
      near the probe tip; 100-ms sonications after craniotomy can create larger and
      more penetrating openings, increasing SPIO leakage ~3.6-fold than 30-ms
      sonications. However, this was accompanied by off-target effects possibly caused
      by ultrasonic wave reflection. SPIO concentrations estimated from transverse
      relaxation rate maps correlated well with direct measurements of SPIO
      concentration by optical emission spectrometry. We have also shown that
      transcranial low-frequency 28-kHz sonication can induce secure BBB opening from
      longitudinal MR image follow up to 7 days. CONCLUSION: This study provides
      valuable information regarding the use low-frequency ultrasound for BBB
      disruption and suggest that SPIO nanoparticles has the potential to serve as a
      thernostic agent in MRI-guided ultrasound-enhanced brain drug delivery.

PMID- 21965169
TI  - Perfusion regulation of hMSC microenvironment and osteogenic differentiation in
      3D scaffold.
AB  - The combination of hMSCs with 3D scaffolds has become an important approach to
      creating functional bone constructs. Bioreactors are important tools to mitigate
      mass transfer limitations and to provide controlled physiochemical and
      biomechanical environments for the 3D bone construct development. Media flow in
      the bioreactor systems is generally controlled either parallel or transverse with
      respect to the 3D construct, creating different cellular and biomechanical
      microenvironments in the 3D constructs. In this study, a custom designed modular
      perfusion bioreactor system was operated under either the parallel or transverse
      flow. The influence of the flow patterns on the characteristics of the hMSCs'
      cellular microenvironment and subsequent construct development was investigated.
      The parallel flow configuration retained ECM proteins and mitogenic growth
      factors within the scaffold, effectively preserving hMSC progenicity and
      proliferation potential (e.g., CFU-F, proliferation, and OCT-4), whereas the
      transverse flow induced hMSC osteogenic differentiation with higher ALP activity
      and calcium deposition and up-regulation of osteogenic bone markers (e.g., BMP-2,
      ALP, RUNX2, OSX, and OC). These results demonstrate the regulatory role of the
      macroscopic flow on the cellular microenvironment of the 3D hMSC construct, and
      suggest configuring media flow as a strategy for directing hMSC fate and 3D bone
      construct development in the perfusion bioreactor.

PMID- 21965170
TI  - Design evaluation and optimisation in crossover pharmacokinetic studies analysed
      by nonlinear mixed effects models.
AB  - Bioequivalence or interaction trials are commonly studied in crossover design and
      can be analysed by nonlinear mixed effects models as an alternative to
      noncompartmental approach. We propose an extension of the population Fisher
      information matrix in nonlinear mixed effects models to design crossover
      pharmacokinetic trials, using a linearisation of the model around the random
      effect expectation, including within-subject variability and discrete covariates
      fixed or changing between periods. We use the expected standard errors of
      treatment effect to compute the power for the Wald test of comparison or
      equivalence and the number of subjects needed for a given power. We perform
      various simulations mimicking crossover two-period trials to show the relevance
      of these developments. We then apply these developments to design a crossover
      pharmacokinetic study of amoxicillin in piglets and implement them in the new
      version 3.2 of the r function PFIM.

PMID- 21965171
TI  - Toward toxicity testing of nanomaterials in the 21st century: a paradigm for
      moving forward.
AB  - A challenge-facing hazard identification and safety evaluation of engineered
      nanomaterials being introduced to market is the diversity and complexity of the
      types of materials with varying physicochemical properties, many of which can
      affect their toxicity by different mechanisms. In general, in vitro test systems
      have limited usefulness for hazard identification of nanoparticles due to various
      issues. Meanwhile, conducting chronic toxicity/carcinogenicity studies in rodents
      for every new nanomaterial introduced into the commerce is impractical if not
      impossible. New toxicity testing systems which rely on predictive, high
      throughput technologies may be the ultimate goal of evaluating the potential
      hazard of nanomaterials. However, at present, this approach alone is unlikely to
      succeed in evaluating the toxicity of the wide array of nanomaterials and
      requires validation from in vivo studies. This article proposes a paradigm for
      toxicity testing and elucidation of the molecular mechanisms of reference
      materials for specific nanomaterial classes/subclasses using short-term in vivo
      animal studies in conjunction with high-throughput screenings and mechanism-based
      short-term in vitro assays. The hazard potential of a particular nanomaterial can
      be evaluated by conducting only in vitro high-throughput assays and mechanistic
      studies and comparing the data with those of the reference materials in the
      specific class/subclass-an approach in line with the vision for 'Toxicity Testing
      in the 21st Century' of chemicals. With well-designed experiments, testing
      nanomaterials of varying/selected physicochemical parameters may be able to
      identify the physicochemical parameters contributing to toxicity. The data so
      derived could be used for the development of computer model systems to predict
      the hazard potential of specific nanoparticles based on property-activity
      relationships.

PMID- 21965172
TI  - Clinical characterization of a newly described neonatal diabetes syndrome caused
      by RFX6 mutations.
AB  - Mutations in the RFX6 gene were recently described to underlie a distinct
      autosomal recessive syndrome of neonatal diabetes comprising intestinal atresia
      and hepatobiliary abnormalities. Until now, only six patients harboring RFX6
      mutations have been reported. We report on a new case due to a novel homozygous
      splice site mutation and update on the clinical outcome of a previously reported
      patient. In addition we review the clinical and molecular features of all RFX6
      mutated cases to better characterize the syndrome. Our results suggest that
      despite the early postnatal fulminant course, patients who survive may expect a
      relatively favorable prognosis.

PMID- 21965173
TI  - Calcium phosphate-based composite nanoparticles in bioimaging and therapeutic
      delivery applications.
AB  - Bioimaging and therapeutic delivery applications are areas of biomedicine where
      nanoparticles have had significant impact, but the use of a nanomaterial in these
      applications can be limited by its physicochemical properties. Calcium phosphate
      based composite nanoparticles are nontoxic and biodegradable, and are therefore
      considered attractive candidates for bioimaging and therapeutic drug delivery
      applications. Also, the pH-dependent solubility profiles of calcium phosphate
      materials make this class of nanoparticles especially useful for in vitro and in
      vivo delivery of dyes, oligonucleotides, and drugs. In this article, we discuss
      how calcium phosphate-based composite nanoparticles fulfill some of the
      requirements typically made for nanoparticles in biomedical applications. We also
      highlight recent studies in bioimaging and therapeutic delivery applications
      focusing on how these studies have addressed some of the challenges associated
      with using these nanoparticles in bioimaging and delivery of therapeutics.

PMID- 21965174
TI  - The myosin family: unconventional roles of actin-dependent molecular motors in
      immune cells.
AB  - Myosins comprise a family of ATP-dependent motor proteins that are best known for
      their role in muscle contraction and their involvement in a wide range of other
      eukaryotic motility processes. Recent phylogenetic analysis places myosins into
      35 highly diverse classes. Although these actin-based molecular motors have been
      characterized extensively, and much is known about their function in different
      cellular compartments, there is little information available about these
      molecules in hematopoietic cells. The available data establish that myosins
      expressed by immune cells are able to support general tasks, such as maintaining
      plasma membrane tension, moving and secreting vesicles, aiding in endo- and
      exocytotic processes, and promoting the adhesion and motility of cells.
      Additionally, however, myosins are involved in highly specialized functions, such
      as regulating cell activation, IS-induced signaling, and the severing of
      microfilaments via the control of GTPases. In this review, we summarize the
      current understanding of myosins in leukocytes, with emphasis on the emerging
      roles of these molecular motors in immune functions.

PMID- 21965175
TI  - Estradiol impairs the Th17 immune response against Candida albicans.
AB  - Candida albicans is a commensal opportunistic pathogen that is also a member of
      gastrointestinal and reproductive tract microbiota. Exogenous factors, such as
      oral contraceptives, hormone replacement therapy, and estradiol, may affect
      susceptibility to Candida infection, although the mechanisms involved in this
      process have not been elucidated. We used a systemic candidiasis model to
      investigate how estradiol confers susceptibility to infection. We report that
      estradiol increases mouse susceptibility to systemic candidiasis, as in vivo and
      ex vivo estradiol-treated DCs were less efficient at up-regulating antigen
      presenting machinery, pathogen killing, migration, IL-23 production, and
      triggering of the Th17 immune response. Based on these results, we propose that
      estradiol impairs DC function, thus explaining the increased susceptibility to
      infection during estrus.

PMID- 21965176
TI  - Palliative care for patients who died in emergency departments: analysis of a
      multicentre cross-sectional survey.
AB  - OBJECTIVES: A growing number of patients die each year in hospital emergency
      departments (EDs). Decisions to withhold or to withdraw life-support therapies
      occur in 80% of patients as described in a multicentre cross-sectional survey
      including 2420 patients. Palliative care has not been explored in patients dying
      in this setting. The aim of this study was to assess the incidence of palliative
      care and to describe this population. METHODS: The authors conducted a post-hoc
      analysis on a cohort of 2420 patients who died in 174 French and Belgian EDs. The
      authors identified patients who benefited from palliative care and described this
      population and the palliative care. RESULTS: Palliative therapies were
      administered to 1373 patients (56.7%). These therapies included administration of
      analgesics, sedation, mouth care, repositioning for comfort (as appropriate) and
      provision of emotional support to the patient and his/her relatives. These
      palliative measures were provided more frequently in the observation unit of the
      ED (n=908, 66.2%) than in an examination room (n=465, 33.8%). Median time
      interval between ED admission and death was longer in patients who received
      palliative care (n=1373) (median, 15 h; first quartile, 6 h; third quartile, 34
      h) than in those who did not (n=1047) (median, 4 h; first quartile, 1 h; third
      quartile, 10 h) (p<10(-4)). CONCLUSIONS: Palliative care is administered to about
      half of the patients who die in EDs. This is insufficient as the majority of the
      patients who died in EDs actually died after a decision to withhold or withdraw
      life-support therapies. End-of-life management must be improved in EDs.

PMID- 21965177
TI  - Current use of early warning scores in UK emergency departments.
AB  - BACKGROUND: There is recent evidence that the modified early warning scoring
      systems (MEWS) in the emergency department (ED) can identify patients at risk of
      deterioration. However, concerns remain that they are not sensitive enough to use
      as a risk assessment tool. OBJECTIVE: To assess use of MEWS in UK EDs. METHODS: A
      postal survey was undertaken of 254 adult EDs within the UK. Questionnaires were
      sent to the clinical lead at each department about their use of early warning
      scoring systems. RESULTS: Responses were received from 145 departments giving a
      response rate of 57%. 87% of respondents are currently using early warning scores
      (EWS). Of those, 80% are using MEWS. In 71% high EWS results in senior ED review,
      however in 25% it does not. Less than half of departments use high MEWS to
      trigger critical care input. 93% of respondents support using EWS in the ED.
      CONCLUSION: Despite the lack of strong evidence, the majority of UK EDs are using
      EWS in some form. MEWS is the most commonly used but departments vary on their
      use of EWS for senior ED and/or critical care review. Over 90% of respondents in
      this survey support EWS in the ED.

PMID- 21965178
TI  - Older people presenting to the emergency department after a fall: a population
      with substantial recurrent healthcare use.
AB  - OBJECTIVES: To document patient characteristics, care pathways, healthcare use
      and costs of fall-related emergency department (ED) presentations by older
      adults. PARTICIPANTS AND METHODS: All fallers aged >=70 years, presenting to the
      ED of a 450-bed metropolitan university hospital in Sydney, Australia (1 April
      2007 through 31 March 2009) were studied. Data were collected from the ED
      electronic information system, ED clinical records and the hospital electronic
      information system database. Population estimates for 2008 for the local areas
      served by the hospital were used to estimate ED presentation rates. RESULTS: Of
      18 902 all-cause ED presentations, 3220 (17.0%) were due to a fall. Among
      fallers, 35.4% had one or more ED presentations and 20.3% had had one or more
      hospital admissions in the preceding 12 months. Fall-related ED presentation led
      directly to hospital admission in 42.7% of the cases, the majority of which
      (78.0%) received acute care only (length of stay-14.4 days for men and 13.7 days
      for women) and the remaining cases underwent further inpatient rehabilitation
      (length of stay 35.6 days for men and 30.1 days for women). After
      hospitalisation, 9.5% of patients became first-time residents of long-term care
      facilities. All fall-related ED presentations and hospitalisations cost a total
      of A$11 241 387 over the study period. CONCLUSIONS: Older fallers presenting to
      the ED consume significant healthcare resources and are an easily identifiable
      high-risk population. They may benefit from systematic fall-risk assessment and
      tailored fall-prevention interventions.

PMID- 21965179
TI  - Nonoperative treatment of PIPJ flexion contractures associated with Dupuytren's
      disease.
AB  - Post-surgical outcomes in patients with Dupuytren's disease causing flexion
      contractures of the proximal interphalangeal joint can be inconsistent and are
      often associated with protracted rehabilitation, reduced flexion, recurrence of
      the contracture, and patient dissatisfaction. An alternative treatment option,
      comprised of splinting and soft tissue mobilization techniques, was introduced to
      stabilize early contractures of the proximal interphalangeal joint in the hopes
      of delaying or obviating surgery. Over the course of approximately 12.6 months
      (+/- 7.8), thirteen patients were followed at the hand clinic at Hotel Dieu
      Hospital in Kingston. One patient was unable to complete the course of therapy.
      Of the remaining patients, analysis showed significant improvement in active
      proximal interphalangeal joint extension of approximately 14.6 degrees  (SD: +/-
      5.1 degrees ; range: 5-25 degrees ) over the course of the treatment (p < .05).
      Nighttime static extension splinting and soft tissue mobilization techniques
      appear to delay and possibly prevent the need for surgery in individuals with
      flexion contractures of the proximal interphalangeal joint due to Dupuytren's
      disease.

PMID- 21965180
TI  - Acute irreducible isolated anterior distal radioulnar joint dislocation.

PMID- 21965181
TI  - Trabecular microstructure of the human lunate in Kienbock's disease.
AB  - The trabecular microstructure of normal lunates and lunates with Kienbock's
      disease was investigated using micro-computed tomography (micro-CT). Five lunates
      with advanced Kienbock's disease were obtained during lunate excision and
      scaphocapitate fusion, and five control lunates were from embalmed cadavers.
      Microstructural morphometric parameters were measured using micro-CT images.
      Trabeculations of lunates with Kienbock's disease were 2.67 times denser and 1.84
      times thicker than those of normal lunates. Furthermore, bone surface areas were
      1.43 times greater and bone volume 2.67 times greater, and structural model
      indices were significantly lower in lunates with Kienbock's disease. The study
      estimated that high mechanical stress would be applied to lunates with Kienbock's
      disease, and suggests that new bone formation and collapse may play important
      roles in the microstructural changes in the lunate with advanced Kienbock's
      disease.

PMID- 21965182
TI  - The role of psychosocial factors in predicting orthodontic treatment outcome at
      the end of 1 year of active treatment.
AB  - The role of psychosocial factors in predicting orthodontic treatment outcome has
      not been investigated before. Thus, the current study aimed to test whether
      psychosocial factors, namely 'daily hassles', resiliency, and family environment,
      can predict orthodontic treatment outcome at the end of 1 year of active
      treatment. A hospital-based, prospective, longitudinal design was adopted
      including 145 consecutively selected 12- to 16-year-old male and female
      adolescents. Baseline psychosocial data were collected by a validated child self
      completed questionnaire before the placement of fixed appliances. Thereafter,
      adolescents were followed up on a monthly basis to collect information relating
      to their daily hassles and treatment adherence. After 1 year of treatment,
      orthodontic treatment outcome was measured by the amount of improvement in
      occlusion achieved. Logistic regression analysis was used. The response rate was
      98.6 per cent and the dropout was 5.6 per cent. Maternal support was an important
      predictor of improvement in occlusion. Adolescents with high levels of maternal
      support were more likely to achieve a high improvement in occlusion than those
      with low levels of maternal support (odds ratio = 3, 95 per cent confidence
      interval = 1.53-6.27, P = 0.002). Paternal support, maternal and paternal
      control, daily hassles, and resiliency were not significantly associated with
      improvement in occlusion (P > 0.05). The regression model confirmed the
      significance of maternal support as a predictor of orthodontic treatment outcome
      at the end of 1 year of active treatment.

PMID- 21965183
TI  - Fatigue and work safety behavior in men during early fatherhood.
AB  - This study investigated the relationship between fatigue and work safety behavior
      of fathers with new babies. A total of 241 fathers completed a questionnaire at 6
      and 12 weeks postpartum with items on fatigue and safety behavior at work.
      Results revealed that fathers worked long hours, reported a moderate-to-high
      physical intensity of work, and experienced interrupted sleep averaging less than
      6 hours. Fathers also reported moderate fatigue at both 6 and 12 weeks postbirth,
      which was inversely related to safety behavior. Both fatigue and sleep history
      made a small but statistically significant contribution to safety behavior
      results at 6 and 12 weeks postbirth. Findings suggest that working fathers with
      babies experience fatigue during early fatherhood and are unable to recover due
      to interrupted and poor sleep patterns. Managers should consider the potential
      for fatigue to compromise work safety and develop risk management strategies that
      target new fathers.

PMID- 21965184
TI  - Prospective study of alcohol consumption quantity and frequency and cancer
      specific mortality in the US population.
AB  - Prospective associations between quantity and frequency of alcohol consumption
      and cancer-specific mortality were studied using a nationally representative
      sample with pooled data from the 1988, 1990, 1991, and 1997-2004 administrations
      of the National Health Interview Survey (n = 323,354). By 2006, 8,362
      participants had died of cancer. Cox proportional hazards regression was used to
      estimate relative risks. Among current alcohol drinkers, for all-site cancer
      mortality, higher-quantity drinking (>= 3 drinks on drinking days vs. 1 drink on
      drinking days) was associated with increased risk among men (relative risk (RR) =
      1.24, 95% confidence interval (CI): 1.09, 1.41; P for linear trend = 0.001);
      higher-frequency drinking (>= 3 days/week vs. <1 day/week) was associated with
      increased risk among women (RR = 1.32, 95% CI: 1.13, 1.55; P-trend < 0.001). Lung
      cancer mortality results were similar, but among never smokers, results were
      null. For colorectal cancer mortality, higher-quantity drinking was associated
      with increased risk among women (RR = 1.93, 95% CI: 1.17, 3.18; P-trend = 0.03).
      Higher-frequency drinking was associated with increased risk of prostate cancer
      (RR = 1.55, 95% CI: 1.01, 2.38; P for quadratic effect = 0.03) and tended to be
      associated with increased risk of breast cancer (RR = 1.44, 95% CI: 0.96, 2.17; P
      trend = 0.06). Epidemiologic studies of alcohol and cancer mortality should
      consider the independent effects of quantity and frequency.

PMID- 21965185
TI  - Missing data methods in Mendelian randomization studies with multiple
      instruments.
AB  - Mendelian randomization studies typically have low power. Where there are several
      valid candidate genetic instruments, precision can be gained by using all the
      instruments available. However, sporadically missing genetic data can offset this
      gain. The authors describe 4 Bayesian methods for imputing the missing data based
      on a missing-at-random assumption: multiple imputations, single nucleotide
      polymorphism (SNP) imputation, latent variables, and haplotype imputation. These
      methods are demonstrated in a simulation study and then applied to estimate the
      causal relation between C-reactive protein and each of fibrinogen and coronary
      heart disease, based on 3 SNPs in British Women's Heart and Health Study
      participants assessed at baseline between May 1999 and June 2000. A complete-case
      analysis based on all 3 SNPs was found to be more precise than analyses using any
      1 SNP alone. Precision is further improved by using any of the 4 proposed missing
      data methods; the improvement is equivalent to about a 25% increase in sample
      size. All methods gave similar results, which were apparently not overly
      sensitive to violation of the missing-at-random assumption. Programming code for
      the analyses presented is available online.

PMID- 21965186
TI  - Proximity to food establishments and body mass index in the Framingham Heart
      Study offspring cohort over 30 years.
AB  - Existing evidence linking residential proximity to food establishments with body
      mass index (BMI; weight (kg)/height (m)(2)) has been inconclusive. In this study,
      the authors assessed the relation between BMI and proximity to food
      establishments over a 30-year period among 3,113 subjects in the Framingham Heart
      Study Offspring Cohort living in 4 Massachusetts towns during 1971-2001. The
      authors used novel data that included repeated measures of BMI and accounted for
      residential mobility and the appearance and disappearance of food establishments.
      They calculated proximity to food establishments as the driving distance between
      each subject's residence and nearby food establishments, divided into 6
      categories. The authors used cross-classified linear mixed models to account for
      time-varying attributes of individuals and residential neighborhoods. Each 1-km
      increase in distance to the closest fast-food restaurant was associated with a
      0.11-unit decrease in BMI (95% credible interval: -0.20, -0.04). In sex
      stratified analyses, this association was present only for women. Other aspects
      of the food environment were either inconsistently associated or not at all
      associated with BMI. Contrary to much prior research, the authors did not find a
      consistent relation between access to fast-food restaurants and individual BMI,
      necessitating a reevaluation of policy discussions on the anticipated impact of
      the food environment on weight gain.

PMID- 21965187
TI  - Misuse of the linear mixed model when evaluating risk factors of cognitive
      decline.
AB  - The linear mixed model (LMM), which is routinely used to describe change in
      outcomes over time and its association with risk factors, assumes that a unit
      change in any predictor is associated with a constant change in the outcome. When
      it is used on psychometric tests, this assumption may not hold. Indeed,
      psychometric tests usually suffer from ceiling and/or floor effects and
      curvilinearity (i.e., varying sensitivity to change). The authors aimed to
      determine the consequences of such misspecification when evaluating predictors of
      cognitive decline. As an alternative to the LMM, they considered 2 mixed models
      based on latent processes that handle discrete and bounded outcomes. Model
      differences are illustrated here using data on 4 psychometric tests from the
      Personnes Agees QUID (PAQUID) Study (1989-2004). The type I error of the Wald
      test for risk-factor regression parameters was formally assessed in a simulation
      study. It demonstrated that type I errors in the LMM could be dramatically
      inflated for some tests, such that spurious associations with risk factors were
      found. In particular, confusion between effects on mean level and effects on
      change over time was highlighted. The authors recommend use of the alternative
      mixed models when studying psychometric tests and more generally quantitative
      scales (quality of life, activities of daily living).

PMID- 21965188
TI  - The long head of the biceps tendon has minimal effect on in vivo glenohumeral
      kinematics: a biplane fluoroscopy study.
AB  - BACKGROUND: The in vivo stabilizing role of the long head of the biceps tendon
      (LHB) is poorly understood. While cadaveric studies report that the loaded LHB
      constrains translations in all directions, clinical data suggest that there is no
      clinically demonstrable alteration in glenohumeral position after LHB tenodesis
      or tenotomy. The purpose of this study was to investigate potential alterations
      in glenohumeral kinematics after LHB tenodesis during 3 dynamic in vivo motions
      using a biplane fluoroscopy system. HYPOTHESIS: Our hypothesis was that there
      would be no difference in glenohumeral translations greater than 1.0 mm between
      shoulders after biceps tenodesis and healthy contralateral shoulders. STUDY
      DESIGN: Controlled laboratory study. METHODS: Five patients who underwent
      unilateral, open subpectoral tenodesis performed abduction, a simulated late
      cocking phase of a throw, and simulated lifting with both their tenodesed
      shoulder and their contralateral healthy shoulder inside a biplane fluoroscopy
      system. Dynamic 3-dimensional glenohumeral positions and electromyography
      activity of the biceps brachii muscle were determined and compared. RESULTS:
      Significant glenohumeral translations occurred in both shoulders for abduction
      (3.4 mm inferiorly; P < .01) and simulated late cocking (2.6 mm anteriorly; P <
      .01). The mean difference for each motion in glenohumeral position between the
      tenodesed and the contralateral healthy shoulders was always less than 1.0 mm.
      The tenodesed shoulders were more anterior (centered) during abduction (0.7 mm; P
      < .01) and for the eccentric phase of the simulated late cocking motion (0.9 mm;
      P < .02). No significant differences were found during the simulated lifting
      motion and in the superior-inferior direction. CONCLUSION: The effect of biceps
      tenodesis on glenohumeral position during the motions studied in vivo was minimal
      compared with physiological translations and interpatient variability. CLINICAL
      RELEVANCE: Our findings demonstrated that LHB tenodesis does not dramatically
      alter glenohumeral position during dynamic motions, suggesting the risk for
      clinically significant alterations in glenohumeral kinematics after tenodesis is
      low in otherwise intact shoulders.

PMID- 21965189
TI  - Sleep disturbance in euthymic bipolar patients.
AB  - Sleep disturbance is a common feature during mood episodes in bipolar disorder.
      The aim of this study was to investigate the prevalence of such symptoms among
      euthymic bipolar patients, and their association with risk for mood episode
      recurrence. A cohort of bipolar I and II subjects participating in the Systematic
      Treatment Enhancement Program for Bipolar Disorder who were euthymic for at least
      8 weeks were included in this analysis. Survival analysis was used to examine the
      association between sleep disturbance on the Montgomery-Asberg Depression Rating
      Scale (MADRS) and recurrence risk. A total of 73/483 bipolar I and II subjects
      reported at least mild sleep disturbance (MADRS sleep item >=2) for the week
      prior to study entry. The presence of sleep problems was associated with a
      history of psychosis, number of previous suicide attempts, and anticonvulsant
      use. Sleep disturbance at study entry was significantly associated with risk for
      mood episode recurrence. Sleep disturbance is not uncommon between episodes for
      individuals with bipolar disorder and may be associated with a more severe course
      of illness. This suggests that sleep disturbance is an important prodromal
      symptom of bipolar disorder and should be considered a target for pharmacologic
      or psychosocial maintenance treatment.

PMID- 21965190
TI  - Involvement of the cholinergic system of CA1 on harmane-induced amnesia in the
      step-down passive avoidance test.
AB  - beta-carboline alkaloids such as harmane (HA) are naturally present in the human
      food chain. They are derived from the plant Peganum harmala and have many
      cognitive effects. In the present study, effects of the nicotinic system of the
      dorsal hippocampus (CA1) on HA-induced amnesia and exploratory behaviors were
      examined. One-trial step-down and hole-board paradigms were used to assess memory
      retention and exploratory behaviors in adult male mice. Pre-training (15 mg/kg)
      but not pre-testing intraperitoneal (i.p.) administration of HA decreased memory
      formation but did not alter exploratory behaviors. Moreover, pre-testing
      administration of nicotine (0.5 ug/mouse, intra-CA1) decreased memory retrieval,
      but induced anxiogenic-like behaviors. On the other hand, pre-test intra-CA1
      injection of ineffective doses of nicotine (0.1 and 0.25 ug/mouse) fully reversed
      HA-induced impairment of memory after pre-training injection of HA (15 mg/kg,
      i.p.) which did not alter exploratory behaviors. Furthermore, pre-testing
      administration of mecamylamine (0.5, 1 and 2 ug/mouse, intra-CA1) did not alter
      memory retrieval but fully reversed HA-induced impairment of memory after pre
      training injection of HA (15 mg/kg, i.p.) which had no effect on exploratory
      behaviors. In conclusion, the present findings suggest the involvement of the
      nicotinic cholinergic system in the HA-induced impairment of memory formation.

PMID- 21965191
TI  - Influence of COMT val158met and ADRA2B deletion polymorphisms on recollection and
      familiarity components of human emotional memory.
AB  - Emotional enhancement of memory is a widely accepted phenomenon that, in addition
      to its adaptive role, may play a role in the evolution of psychiatric disorders.
      Hence a comprehensive understanding of its neurobiological basis is imperative.
      Whilst the pharmacological and neural mechanisms are well known, the contribution
      of genetic variation is not. Research suggests that two qualitatively different
      processes (recollection and familiarity) contribute to recognition memory. In
      this study, we examined the relative contribution of two common genetic
      polymorphisms, the deletion variant of the ADRA2B gene that codes the alpha2b
      adrenergic receptor and the val158met polymorphism of the COMT gene that codes
      the catechol-O-methyltransferase enzyme, to emotional enhancement of these two
      memory processes in 97 healthy male volunteers. There was a significant
      interaction between COMT genotype and emotional arousal in relation to
      recollection, but not familiarity, with the former being significantly elevated
      for emotionally arousing versus neutral pictures in carriers of the val158 allele
      compared with met158 carriers. There were no main effects or interactions in
      relation to ADRA2B genotype.

PMID- 21965192
TI  - Combined beta-adrenergic and corticosteroid receptor activation regulates AMPA
      receptor function in hippocampal neurons.
AB  - Shortly after stress, limbic neurons are exposed to high levels of noradrenaline
      and corticosterone. These hormones are necessary for optimal behavioural
      adaptation. Behavioural effects critically depend on noradrenaline acting via
      beta-adrenergic receptors, but these effects are strongly modulated by
      corticosterone, indicating putative interactions between the two hormones. Since
      both noradrenaline and corticosterone are known to quickly affect properties of
      AMPA-type glutamate receptors (AMPAR), we here examined - in hippocampal neurons 
      three parameters which give insight in the functionality of AMPARs:
      phosphorylation, surface expression and spontaneous synaptic transmission. In
      homogenates of adult hippocampal slices, application of corticosterone (30 nM for
      15 min) by itself did not affect phosphorylation of the AMPAR GluA1 subunit at
      S845 or S831. Co-application of the beta-adrenergic receptor agonist
      isoproterenol (10 uM) largely increased S845 (but not S831) phosphorylation.
      Corticosterone also did not change GluA1 and GluA2 surface expression in
      hippocampal primary cultures. However, combined administration of corticosterone
      and 1 uM isoproterenol - which by itself was ineffective - enhanced surface
      expression. Interestingly, 10 uM isoproterenol alone enhanced GluA1 surface
      expression, but this was decreased by corticosterone. Finally, in hippocampal
      primary cultures, the inter-event interval of miniature excitatory postsynaptic
      currents (mEPSCs) was decreased by the combination of 1 uM isoproterenol and
      corticosterone (which were ineffective by themselves) while the same combination
      did not affect the amplitude. We conclude that AMPAR phosphorylation, surface
      expression and mEPSC inter-event interval respond most strongly to a combination
      of corticosterone and beta-adrenergic receptors. These combined hormonal effects
      on glutamate transmission might contribute to their memory-enhancing effects.

PMID- 21965193
TI  - Experimental microsphere targeting in a representative hepatic artery system.
AB  - Recent work employing the computational fluid-particle modeling of the hepatic
      arteries has identified a correlation between particle release position and
      downstream branch distribution for direct tumor-targeting in radioembolization
      procedures. An experimental model has been constructed to evaluate the underlying
      simulation theory and determine its feasibility for future clinical use. A scaled
      model of a generalized hepatic system with a single inlet and five outlet
      branches was fabricated to replicate the fluid dynamics in the hepatic arteries
      of diseased livers. Assuming steady flow, neutrally buoyant microspheres were
      released from controlled locations within the inlet of the model and the
      resulting output distributions were recorded. Fluid and particle transport
      simulations were conducted with identical parameters. The resulting
      experimentally and simulation-derived microsphere distributions were compared.
      The experimental microsphere distribution exhibited a clear dependence on
      injection location that correlated very strongly with the computationally
      predicted results. Individual branch targeting was possible for each of the five
      outputs. The experimental results validate the simulation methodology for
      achieving targeted microsphere distributions in a known geometry under constant
      flow conditions.

PMID- 21965194
TI  - Evaluation of segmentation algorithms on cell populations using CDF curves.
AB  - Cell segmentation is a critical step in the analysis pipeline for most imaging
      cytometry experiments and evaluating the performance of segmentation algorithms
      is important for aiding the selection of segmentation algorithms. Four popular
      algorithms are evaluated based on their cell segmentation performance. Because
      segmentation involves the classification of pixels belonging to regions within
      the cell or belonging to background, these algorithms are evaluated based on
      their total misclassification error. Misclassification error is particularly
      relevant in the analysis of quantitative descriptors of cell morphology involving
      pixel counts, such as projected area, aspect ratio and diameter. Since the
      cumulative distribution function captures completely the stochastic properties of
      a population of misclassification errors it is used to compare segmentation
      performance.

PMID- 21965195
TI  - Performance analysis for magnetic resonance imaging with nonlinear encoding
      fields.
AB  - Nonlinear spatial encoding fields for magnetic resonance imaging (MRI) hold great
      promise to improve on the linear gradient approaches by, for example, enabling
      reduced imaging times. Imaging schemes that employ general nonlinear encoding
      fields are difficult to analyze using traditional measures. In particular, the
      resolution is spatially varying, characterized by a position-dependent point
      spread function (PSF). Likewise, the use of nonlinear encoding fields creates an
      additional spatial dependence on the signal-to-noise ratio (SNR). Although the
      two properties of resolution and SNR are linked, in this work we focus on the
      latter. To this end, we examine the pixel variance, which requires a computation
      that is often not feasible for nonlinear encoding schemes. This paper presents a
      general formulation for the performance analysis of imaging schemes using
      arbitrary encoding fields. The analysis leads to the derivation of a practical
      and computationally efficient performance metric, which is demonstrated through
      simulation examples.

PMID- 21965197
TI  - Decentralized optimal control of a class of interconnected nonlinear discrete
      time systems by using online Hamilton-Jacobi-Bellman formulation.
AB  - In this paper, the direct neural dynamic programming technique is utilized to
      solve the Hamilton-Jacobi-Bellman equation forward-in-time for the decentralized
      near optimal regulation of a class of nonlinear interconnected discrete-time
      systems with unknown internal subsystem and interconnection dynamics, while the
      input gain matrix is considered known. Even though the unknown interconnection
      terms are considered weak and functions of the entire state vector, the
      decentralized control is attempted under the assumption that only the local state
      vector is measurable. The decentralized nearly optimal controller design for each
      subsystem consists of two neural networks (NNs), an action NN that is aimed to
      provide a nearly optimal control signal, and a critic NN which evaluates the
      performance of the overall system. All NN parameters are tuned online for both
      the NNs. By using Lyapunov techniques it is shown that all subsystems signals are
      uniformly ultimately bounded and that the synthesized subsystems inputs approach
      their corresponding nearly optimal control inputs with bounded error. Simulation
      results are included to show the effectiveness of the approach.

PMID- 21965196
TI  - Improved regional activity quantitation in nuclear medicine using a new approach
      to correct for tissue partial volume and spillover effects.
AB  - We have developed a new method of compensating for effects of partial volume and
      spillover in dual-modality imaging. The approach requires segmentation of just a
      few tissue types within a small volume-of-interest (VOI) surrounding a lesion;
      the algorithm estimates simultaneously, from projection data, the activity
      concentration within each segmented tissue inside the VOI. Measured emission
      projections were fitted to the sum of resolution-blurred projections of each such
      tissue, scaled by its unknown activity concentration, plus a global background
      contribution obtained by reprojection through the reconstructed image volume
      outside the VOI. The method was evaluated using multiple-pinhole MUSPECT data
      simulated for the MOBY mouse phantom containing two spherical lung tumors and one
      liver tumor, as well as using multiple-bead phantom data acquired on MUSPECT and
      MUCT scanners. Each VOI in the simulation study was 4.8 mm (12 voxels) cubed and,
      depending on location, contained up to four tissues (tumor, liver, heart, lung)
      with different values of relative (99m)Tc concentration. All tumor activity
      estimates achieved bias after ~ 15 ordered-subsets expectation maximization
      (OSEM) iterations (*10 subsets) , with better than 8% precision ( <= 25% greater
      than the Cramer-Rao lower bound). The projection-based fitting approach also
      outperformed three standardized uptake value (SUV)-like metrics, one of which was
      corrected for count spillover. In the bead phantom experiment, the mean +/-
      standard deviation of the bias of VOI estimates of bead concentration were 0.9+/
      9.5%, comparable to those of a perturbation geometric transfer matrix (pGTM)
      approach (-5.4+/-8.6%); however, VOI estimates were more stable with increasing
      iteration number than pGTM estimates, even in the presence of substantial axial
      misalignment between MUCT and MUSPECT image volumes.

PMID- 21965198
TI  - Spectral embedded clustering: a framework for in-sample and out-of-sample
      spectral clustering.
AB  - Spectral clustering (SC) methods have been successfully applied to many real
      world applications. The success of these SC methods is largely based on the
      manifold assumption, namely, that two nearby data points in the high-density
      region of a low-dimensional data manifold have the same cluster label. However,
      such an assumption might not always hold on high-dimensional data. When the data
      do not exhibit a clear low-dimensional manifold structure (e.g., high-dimensional
      and sparse data), the clustering performance of SC will be degraded and become
      even worse than  K -means clustering. In this paper, motivated by the observation
      that the true cluster assignment matrix for high-dimensional data can be always
      embedded in a linear space spanned by the data, we propose the spectral embedded
      clustering (SEC) framework, in which a linearity regularization is explicitly
      added into the objective function of SC methods. More importantly, the proposed
      SEC framework can naturally deal with out-of-sample data. We also present a new
      Laplacian matrix constructed from a local regression of each pattern and
      incorporate it into our SEC framework to capture both local and global
      discriminative information for clustering. Comprehensive experiments on eight
      real-world high-dimensional datasets demonstrate the effectiveness and advantages
      of our SEC framework over existing SC methods and  K-means-based clustering
      methods. Our SEC framework significantly outperforms SC using the Nystrom
      algorithm on unseen data.

PMID- 21965199
TI  - A nonlinear control method based on ANFIS and multiple models for a class of SISO
      nonlinear systems and its application.
AB  - This paper presents a novel nonlinear control strategy for a class of uncertain
      single-input and single-output discrete-time nonlinear systems with unstable zero
      dynamics. The proposed method combines adaptive-network-based fuzzy inference
      system (ANFIS) with multiple models, where a linear robust controller, an ANFIS
      based nonlinear controller and a switching mechanism are integrated using
      multiple models technique. It has been shown that the linear controller can
      ensure the boundedness of the input and output signals and the nonlinear
      controller can improve the dynamic performance of the closed loop system.
      Moreover, it has also been shown that the use of the switching mechanism can
      simultaneously guarantee the closed loop stability and improve its performance.
      As a result, the controller has the following three outstanding features compared
      with existing control strategies. First, this method relaxes the assumption of
      commonly-used uniform boundedness on the unmodeled dynamics and thus enhances its
      applicability. Second, since ANFIS is used to estimate and compensate the effect
      caused by the unmodeled dynamics, the convergence rate of neural network learning
      has been increased. Third, a "one-to-one mapping" technique is adapted to
      guarantee the universal approximation property of ANFIS. The proposed controller
      is applied to a numerical example and a pulverizing process of an alumina
      sintering system, respectively, where its effectiveness has been justified.

PMID- 21965200
TI  - Generalized constraint neural network regression model subject to linear priors.
AB  - This paper is reports an extension of our previous investigations on adding
      transparency to neural networks. We focus on a class of linear priors (LPs), such
      as symmetry, ranking list, boundary, monotonicity, etc., which represent either
      linear-equality or linear-inequality priors. A generalized constraint neural
      network-LPs (GCNN-LPs) model is studied. Unlike other existing modeling
      approaches, the GCNN-LP model exhibits its advantages. First, any LP is embedded
      by an explicitly structural mode, which may add a higher degree of transparency
      than using a pure algorithm mode. Second, a direct elimination and least squares
      approach is adopted to study the model, which produces better performances in
      both accuracy and computational cost over the Lagrange multiplier techniques in
      experiments. Specific attention is paid to both "hard (strictly satisfied)" and
      "soft (weakly satisfied)" constraints for regression problems. Numerical
      investigations are made on synthetic examples as well as on the real-world
      datasets. Simulation results demonstrate the effectiveness of the proposed
      modeling approach in comparison with other existing approaches.

PMID- 21965201
TI  - Stability and convergence analysis for a class of neural networks.
AB  - In this paper, we analyze and establish the stability and convergence of the
      dynamical system proposed by Xia and Feng, whose equilibria solve variational
      inequality and related problems. Under the pseudo-monotonicity and other
      conditions, this system is proved to be stable in the sense of Lyapunov and
      converges to one of its equilibrium points for any starting point. Meanwhile, the
      global exponential stability of this system is also shown under some mild
      conditions without the strong monotonicity of the mapping. The obtained results
      improve and correct some existing ones. The validity and performance of this
      system are demonstrated by some numerical examples.

PMID- 21965202
TI  - Robust initialization of a Jordan network with recurrent constrained learning.
AB  - In this paper, we propose a robust initialization of a Jordan network with a
      recurrent constrained learning (RIJNRCL) algorithm for multilayered recurrent
      neural networks (RNNs). This novel algorithm is based on the constrained learning
      concept of the Jordan network with a recurrent sensitivity and weight convergence
      analysis, which is used to obtain a tradeoff between the training and testing
      errors. In addition to using classical techniques for the adaptive learning rate
      and the adaptive dead zone, RIJNRCL employs a recurrent constrained parameter
      matrix to switch off excessive contributions from the hidden layer neurons based
      on weight convergence and stability conditions of the multilayered RNNs. It is
      well known that a good response from the hidden layer neurons and proper
      initialization play a dominant role in avoiding local minima in multilayered
      RNNs. The new RIJNRCL algorithm solves the twin problems of weight initialization
      and selection of the hidden layer neurons via a novel recurrent sensitivity ratio
      analysis. We provide the detailed steps for using RIJNRCL in a few benchmark time
      series prediction problems and show that the proposed algorithm achieves superior
      generalization performance.

PMID- 21965203
TI  - Efficient object tracking by incremental self-tuning particle filtering on the
      affine group.
AB  - We propose an incremental self-tuning particle filtering (ISPF) framework for
      visual tracking on the affine group, which can find the optimal state in a
      chainlike way with a very small number of particles. Unlike traditional particle
      filtering, which only relies on random sampling for state optimization, ISPF
      incrementally draws particles and utilizes an online-learned pose estimator (PE)
      to iteratively tune them to their neighboring best states according to some
      feedback appearance-similarity scores. Sampling is terminated if the maximum
      similarity of all tuned particles satisfies a target-patch similarity
      distribution modeled online or if the permitted maximum number of particles is
      reached. With the help of the learned PE and some appearance-similarity feedback
      scores, particles in ISPF become "smart" and can automatically move toward the
      correct directions; thus, sparse sampling is possible. The optimal state can be
      efficiently found in a step-by-step way in which some particles serve as bridge
      nodes to help others to reach the optimal state. In addition to the single-target
      scenario, the "smart" particle idea is also extended into a multitarget tracking
      problem. Experimental results demonstrate that our ISPF can achieve great
      robustness and very high accuracy with only a very small number of particles.

PMID- 21965204
TI  - Image quality assessment by visual gradient similarity.
AB  - A full-reference image quality assessment (IQA) model by multiscale visual
      gradient similarity (VGS) is presented. The VGS model adopts a three-stage
      approach: First, global contrast registration for each scale is applied. Then,
      pointwise comparison is given by multiplying the similarity of gradient direction
      with the similarity of gradient magnitude. Third, intrascale pooling is applied,
      followed by interscale pooling. Several properties of human visual systems on
      image gradient have been explored and incorporated into the VGS model. It has
      been found that Stevens' power law is also suitable for gradient magnitude. Other
      factors such as quality uniformity, visual detection threshold of gradient, and
      visual frequency sensitivity also affect subjective image quality. The optimal
      values of two parameters of VGS are trained with existing IQA databases, and good
      performance of VGS has been verified by cross validation. Experimental results
      show that VGS is competitive with state-of-the-art metrics in terms of prediction
      precision, reliability, simplicity, and low computational cost.

PMID- 21965205
TI  - Discriminant learning through multiple principal angles for visual recognition.
AB  - Canonical correlation has been prevalent for multiset-based pairwise subspace
      analysis. As an extension, discriminant canonical correlations (DCCs) have been
      developed for classification purpose by learning a global subspace based on
      Fisher discriminant modeling of pairwise subspaces. However, the discriminative
      power of DCCs is not optimal as it only measures the "local" canonical
      correlations within subspace pairs, which lacks the "global" measurement among
      all the subspaces. In this paper, we propose a multiset discriminant canonical
      correlation method, i.e., multiple principal angle (MPA). It jointly considers
      both "local" and "global" canonical correlations by iteratively learning multiple
      subspaces (one for each set) as well as a global discriminative subspace, on
      which the angle among multiple subspaces of the same class is minimized while
      that of different classes is maximized. The proposed computational solution is
      guaranteed to be convergent with much faster converging speed than DCC. Extensive
      experiments on pattern recognition applications demonstrate the superior
      performance of MPA compared to existing subspace learning methods.

PMID- 21965206
TI  - Iterative channel decoding of FEC-based multiple-description codes.
AB  - Multiple description coding has been receiving attention as a robust transmission
      framework for multimedia services. This paper studies the iterative decoding of
      FEC-based multiple description codes. The proposed decoding algorithms take
      advantage of the error detection capability of Reed-Solomon (RS) erasure codes.
      The information of correctly decoded RS codewords is exploited to enhance the
      error correction capability of the Viterbi algorithm at the next iteration of
      decoding. In the proposed algorithm, an intradescription interleaver is
      synergistically combined with the iterative decoder. The interleaver does not
      affect the performance of noniterative decoding but greatly enhances the
      performance when the system is iteratively decoded. We also address the optimal
      allocation of RS parity symbols for unequal error protection. For the optimal
      allocation in iterative decoding, we derive mathematical equations from which the
      probability distributions of description erasures can be generated in a simple
      way. The performance of the algorithm is evaluated over an orthogonal frequency
      division multiplexing system. The results show that the performance of the
      multiple description codes is significantly enhanced.

PMID- 21965207
TI  - S3: a spectral and spatial measure of local perceived sharpness in natural
      images.
AB  - This paper presents an algorithm designed to measure the local perceived
      sharpness in an image. Our method utilizes both spectral and spatial properties
      of the image: For each block, we measure the slope of the magnitude spectrum and
      the total spatial variation. These measures are then adjusted to account for
      visual perception, and then, the adjusted measures are combined via a weighted
      geometric mean. The resulting measure, i.e.,   S(3) (spectral and spatial
      sharpness), yields a perceived sharpness map in which greater values denote
      perceptually sharper regions. This map can be collapsed into a single index,
      which quantifies the overall perceived sharpness of the whole image. We
      demonstrate the utility of the  S(3) measure for within-image and across-image
      sharpness prediction, no-reference image quality assessment of blurred images,
      and monotonic estimation of the standard deviation of the impulse response used
      in Gaussian blurring. We further evaluate the accuracy of  S(3)  in local
      sharpness estimation by comparing   S(3) maps to sharpness maps generated by
      human subjects. We show that  S(3)  can generate sharpness maps, which are highly
      correlated with the human-subject maps.

PMID- 21965208
TI  - Snakes with an ellipse-reproducing property.
AB  - We present a new class of continuously defined parametric snakes using a special
      kind of exponential splines as basis functions. We have enforced our bases to
      have the shortest possible support subject to some design constraints to maximize
      efficiency. While the resulting snakes are versatile enough to provide a good
      approximation of any closed curve in the plane, their most important feature is
      the fact that they admit ellipses within their span. Thus, they can perfectly
      generate circular and elliptical shapes. These features are appropriate to
      delineate cross sections of cylindrical-like conduits and to outline bloblike
      objects. We address the implementation details and illustrate the capabilities of
      our snake with synthetic and real data.

PMID- 21965209
TI  - Jointly optimized spatial prediction and block transform for video and image
      coding.
AB  - This paper proposes a novel approach to jointly optimize spatial prediction and
      the choice of the subsequent transform in video and image compression. Under the
      assumption of a separable first-order Gauss-Markov model for the image signal, it
      is shown that the optimal Karhunen-Loeve Transform, given available partial
      boundary information, is well approximated by a close relative of the discrete
      sine transform (DST), with basis vectors that tend to vanish at the known
      boundary and maximize energy at the unknown boundary. The overall intraframe
      coding scheme thus switches between this variant of the DST named asymmetric DST
      (ADST), and traditional discrete cosine transform (DCT), depending on prediction
      direction and boundary information. The ADST is first compared with DCT in terms
      of coding gain under ideal model conditions and is demonstrated to provide
      significantly improved compression efficiency. The proposed adaptive prediction
      and transform scheme is then implemented within the H.264/AVC intra-mode
      framework and is experimentally shown to significantly outperform the standard
      intra coding mode. As an added benefit, it achieves substantial reduction in
      blocking artifacts due to the fact that the transform now adapts to the
      statistics of block edges. An integer version of this ADST is also proposed.

PMID- 21965210
TI  - Gradient-directed multiexposure composition.
AB  - In this paper, we present a simple yet effective method that takes advantage of
      the gradient information to accomplish the multiexposure image composition in
      both static and dynamic scenes. Given multiple images with different exposures,
      the proposed approach is capable of producing a pleasant tone-mapped-like high
      dynamic-range image by compositing them seamlessly with the guidance of gradient
      based quality assessment. In particular, two novel quality measures, namely,
      visibility and consistency, are developed based on the observations of gradient
      changes among different exposures. Experiments in various static and dynamic
      scenes are conducted to demonstrate the effectiveness of the proposed method.

PMID- 21965211
TI  - Implicit polynomial representation through a fast fitting error estimation.
AB  - This paper presents a simple distance estimation for implicit polynomial fitting.
      It is computed as the height of a simplex built between the point and the surface
      (i.e., a triangle in 2-D or a tetrahedron in 3-D), which is used as a coarse but
      reliable estimation of the orthogonal distance. The proposed distance can be
      described as a function of the coefficients of the implicit polynomial. Moreover,
      it is differentiable and has a smooth behavior . Hence, it can be used in any
      gradient-based optimization. In this paper, its use in a Levenberg-Marquardt
      framework is shown, which is particularly devoted for nonlinear least squares
      problems. The proposed estimation is a generalization of the gradient-based
      distance estimation, which is widely used in the literature. Experimental
      results, both in 2-D and 3-D data sets, are provided. Comparisons with state-of
      the-art techniques are presented, showing the advantages of the proposed
      approach.

PMID- 21965212
TI  - Camera constraint-free view-based 3-D object retrieval.
AB  - Recently, extensive research efforts have been dedicated to view-based methods
      for 3-D object retrieval due to the highly discriminative property of multiviews
      for 3-D object representation. However, most of state-of-the-art approaches
      highly depend on their own camera array settings for capturing views of 3-D
      objects. In order to move toward a general framework for 3-D object retrieval
      without the limitation of camera array restriction, a camera constraint-free view
      based (CCFV) 3-D object retrieval algorithm is proposed in this paper. In this
      framework, each object is represented by a free set of views, which means that
      these views can be captured from any direction without camera constraint. For
      each query object, we first cluster all query views to generate the view
      clusters, which are then used to build the query models. For a more accurate 3-D
      object comparison, a positive matching model and a negative matching model are
      individually trained using positive and negative matched samples, respectively.
      The CCFV model is generated on the basis of the query Gaussian models by
      combining the positive matching model and the negative matching model. The CCFV
      removes the constraint of static camera array settings for view capturing and can
      be applied to any view-based 3-D object database. We conduct experiments on the
      National Taiwan University 3-D model database and the ETH 3-D object database.
      Experimental results show that the proposed scheme can achieve better performance
      than state-of-the-art methods.

PMID- 21965213
TI  - Co-transduction for shape retrieval.
AB  - In this paper, we propose a new shape/object retrieval algorithm, namely, co
      transduction. The performance of a retrieval system is critically decided by the
      accuracy of adopted similarity measures (distances or metrics). In shape/object
      retrieval, ideally, intraclass objects should have smaller distances than
      interclass objects. However, it is a difficult task to design an ideal metric to
      account for the large intraclass variation. Different types of measures may focus
      on different aspects of the objects: for example, measures computed based on
      contours and skeletons are often complementary to each other. Our goal is to
      develop an algorithm to fuse different similarity measures for robust shape
      retrieval through a semisupervised learning framework. We name our method co
      transduction, which is inspired by the co-training algorithm. Given two
      similarity measures and a query shape, the algorithm iteratively retrieves the
      most similar shapes using one measure and assigns them to a pool for the other
      measure to do a re-ranking, and vice versa. Using co-transduction, we achieved an
      improved result of 97.72% (bull's-eye measure) on the MPEG-7 data set over the
      state-of-the-art performance. We also present an algorithm called tri
      transduction to fuse multiple-input similarities, and it achieved 99.06% on the
      MPEG-7 data set. Our algorithm is general, and it can be directly applied on
      input similarity measures/metrics; it is not limited to object shape retrieval
      and can be applied to other tasks for ranking/retrieval.

PMID- 21965214
TI  - SVD-based quality metric for image and video using machine learning.
AB  - We study the use of machine learning for visual quality evaluation with
      comprehensive singular value decomposition (SVD)-based visual features. In this
      paper, the two-stage process and the relevant work in the existing visual quality
      metrics are first introduced followed by an in-depth analysis of SVD for visual
      quality assessment. Singular values and vectors form the selected features for
      visual quality assessment. Machine learning is then used for the feature pooling
      process and demonstrated to be effective. This is to address the limitations of
      the existing pooling techniques, like simple summation, averaging, Minkowski
      summation, etc., which tend to be ad hoc. We advocate machine learning for
      feature pooling because it is more systematic and data driven. The experiments
      show that the proposed method outperforms the eight existing relevant schemes.
      Extensive analysis and cross validation are performed with ten publicly available
      databases (eight for images with a total of 4042 test images and two for video
      with a total of 228 videos). We use all publicly accessible software and
      databases in this study, as well as making our own software public, to facilitate
      comparison in future research.

PMID- 21965215
TI  - Development and evaluation of an ambulatory stress monitor based on wearable
      sensors.
AB  - Chronic stress is endemic to modern society. However, as it is unfeasible for
      physicians to continuously monitor stress levels, its diagnosis is nontrivial.
      Wireless body sensor networks offer opportunities to ubiquitously detect and
      monitor mental stress levels, enabling improved diagnosis, and early treatment.
      This article describes the development of a wearable sensor platform to monitor a
      number of physiological correlates of mental stress. We discuss tradeoffs in both
      system design and sensor selection to balance information content and
      wearability. Using experimental signals collected from the wearable sensor, we
      describe a selected number of physiological features that show good correlation
      with mental stress. In particular, we propose a new spectral feature that
      estimates the balance of the autonomic nervous system by combining information
      from the power spectral density of respiration and heart rate variability. We
      validate the effectiveness of our approach on a binary discrimination problem
      when subjects are placed under two psychophysiological conditions: mental stress
      and relaxation. When used in a logistic regression model, our feature set is able
      to discriminate between these two mental states with a success rate of 81% across
      subjects.

PMID- 21965219
TI  - Exposure to silver nanoparticles inhibits selenoprotein synthesis and the
      activity of thioredoxin reductase.
AB  - BACKGROUND: Silver nanoparticles (AgNPs) and silver (Ag)-based materials are
      increasingly being incorporated into consumer products, and although humans have
      been exposed to colloidal Ag in many forms for decades, this rise in the use of
      Ag materials has spurred interest into their toxicology. Recent reports have
      shown that exposure to AgNPs or Ag ions leads to oxidative stress, endoplasmic
      reticulum stress, and reduced cell proliferation. Previous studies have shown
      that Ag accumulates in tissues as silver sulfides (Ag2S) and silver selenide
      (Ag2Se). OBJECTIVES: In this study we investigated whether exposure of cells in
      culture to AgNPs or Ag ions at subtoxic doses would alter the effective
      metabolism of selenium, that is, the incorporation of selenium into
      selenoproteins. METHODS: For these studies we used a keratinocyte cell model
      (HaCat) and a lung cell model (A549). We also tested (in vitro, both cellular and
      chemical) whether Ag ions could inhibit the activity of a key selenoenzyme,
      thioredoxin reductase (TrxR). RESULTS: We found that exposure to AgNPs or far
      lower levels of Ag ions led to a dose-dependent inhibition of selenium metabolism
      in both cell models. The synthesis of protein was not altered under these
      conditions. Exposure to nanomolar levels of Ag ions effectively blocked selenium
      metabolism, suggesting that Ag ion leaching was likely the mechanism underlying
      observed changes during AgNP exposure. Exposure likewise inhibited TrxR activity
      in cultured cells, and Ag ions were potent inhibitors of purified rat TrxR
      isoform 1 (cytosolic) (TrxR1) enzyme. CONCLUSIONS: Exposure to AgNPs leads to the
      inhibition of selenoprotein synthesis and inhibition of TrxR1. Further, we
      propose these two sites of action comprise the likely mechanism underlying
      increases in oxidative stress, increases endoplasmic reticulum stress, and
      reduced cell proliferation during exposure to Ag.

PMID- 21965221
TI  - Association of soluble tumour necrosis factor-related apoptosis-inducing ligand
      levels with coronary plaque burden and composition.
AB  - BACKGROUND: Evidence shows that the soluble tumour necrosis factor-related
      apoptosis-inducing ligand (sTRAIL) may play a protective role against
      atherosclerosis. This study sought to investigate the potential association of
      sTRAIL levels with intravascular ultrasound (IVUS) and virtual histology
      characteristics of coronary plaques. METHODS: Patients with stable angina or
      positive for ischaemia non-invasive test were submitted to left cardiac
      catheterisation. Coronary blood samples were collected and sTRAIL was measured.
      Coronary arteries with at least one 50% or greater stenosis were studied with
      IVUS. RESULTS: 56 coronary arteries were studied with significant coronary artery
      disease. Plaque volume per unit of arterial length was 63 +/- 5 mm(3)/cm in
      arteries at the lower quartile of sTRAIL concentration versus 30 +/- 4 mm(3)/cm
      at the upper quartile (p<0.001; 95% CI of the difference 19.7 to 46.3 mm(3)/cm).
      The necrotic core and fibrofatty content of atheromatous plaques were inversely
      associated with sTRAIL (p<0.001). Thin-cap fibroatheromas (TCFA) were discovered
      in 16 of the 56 arterial segments. The mean sTRAIL concentration in these
      segments was 56.8 +/- 7.5 pg/ml versus 99.9 +/- 5.7 pg/ml in those without TCFA
      (p<0.001; 95% CI of the difference 22.7 to 63.5 pg/ml). The association of sTRAIL
      with the presence of TCFA remained significant in the logistic multivariate
      analysis (p=0.009). CONCLUSION: According to the findings of the present study,
      in addition to coronary artery disease burden, the sTRAIL concentration is also
      related to the composition of atheromatous plaques. A significant association is
      demonstrated between low sTRAIL levels and the presence of TCFA, the IVUS-virtual
      histology prototype of the vulnerable plaque.

PMID- 21965220
TI  - Quality of online pharmacies and websites selling prescription drugs: a
      systematic review.
AB  - BACKGROUND: Online pharmacies are companies that sell pharmaceutical
      preparations, including prescription-only drugs, on the Internet. Very little is
      known about this phenomenon because many online pharmacies operate from remote
      countries, where legal bases and business practices are largely inaccessible to
      international research. OBJECTIVE: The aim of the study was to perform an up-to
      date and comprehensive review of the scientific literature focusing on the
      broader picture of online pharmacies by scanning several scientific and
      institutional databases, with no publication time limits. METHODS: We searched 4
      electronic databases up to January 2011 and the gray literature on the Internet
      using the Google search engine and its tool Google Scholar. We also investigated
      the official websites of institutional agencies (World Health Organization, and
      US and European centers for disease control and drug regulation authorities). We
      focused specifically on online pharmacies offering prescription-only drugs. We
      decided to analyze and report only articles with original data, in order to
      review all the available data regarding online pharmacies and their usage.
      RESULTS: We selected 193 relevant articles: 76 articles with original data, and
      117 articles without original data (editorials, regulation articles, or the like)
      including 5 reviews. The articles with original data cover samples of online
      pharmacies in 47 cases, online drug purchases in 13, consumer characteristics in
      15, and case reports on adverse effects of online drugs in 12. The studies show
      that random samples with no specific limits to prescription requirements found
      that at least some websites sold drugs without a prescription and that an online
      questionnaire was a frequent tool to replace prescription. Data about
      geographical characteristics show that this information can be concealed in many
      websites. The analysis of drug offer showed that online a consumer can get
      virtually everything. Regarding quality of drugs, researchers very often found
      inappropriate packaging and labeling, whereas the chemical composition usually
      was not as expected in a minority of the studies' samples. Regarding consumers,
      the majority of studies found that not more than 6% of the samples had bought
      drugs online. CONCLUSIONS: Online pharmacies are an important phenomenon that is
      continuing to spread, despite partial regulation, due to intrinsic difficulties
      linked to the impalpable and evanescent nature of the Web and its global
      dimension. To enhance the benefits and minimize the risks of online pharmacies, a
      2-level approach could be adopted. The first level should focus on policy, with
      laws regulating the phenomenon at an international level. The second level needs
      to focus on the individual. This approach should aim to increase health literacy,
      required for making appropriate health choices, recognizing risks and making the
      most of the multitude of opportunities offered by the world of medicine 2.0.

PMID- 21965222
TI  - Total desmosines in plasma and urine correlate with lung function.
AB  - The aim of the present study was to evaluate the relationship between the matrix
      degradation biomarkers, desmosine and isodesmosine (desmosines), and lung
      function. Plasma and creatinine-corrected urinary total desmosines (P- and U
      desmosines, respectively), lung function and diffusing capacity of the lung for
      carbon monoxide (D(L,CO)) were measured in a cohort of subjects from the Swedish
      Twin Registry. Concentrations of U- and P-desmosines were measured in 349 and 318
      subjects, respectively; approximately one-third of subjects had chronic
      obstructive pulmonary disease (COPD). Age, female sex, body mass index (BMI) and
      smoking were significantly associated with U-desmosines in a multiple linear
      regression analysis. In the overall population, after adjustments for age, sex,
      height, BMI and smoking, concentrations of U-desmosines were significantly
      correlated with all lung function measures, and P-desmosines with forced
      expiratory volume in 1 s and D(L,CO) (p<0.05). With the exception of residual
      volume versus P-desmosines, relationships between concentrations of desmosines
      and lung function measures were markedly stronger in subjects with COPD compared
      with those without COPD. These cross-sectional data showing associations between
      desmosines and several lung function variables suggest that desmosines,
      particularly U-desmosines, could be a useful biomarker of COPD status.

PMID- 21965223
TI  - Pulmonary embolism: CT signs and cardiac biomarkers for predicting right
      ventricular dysfunction.
AB  - The aim of this study was to prospectively evaluate the accuracy of quantitative
      cardiac computed tomography (CT) parameters and two cardiac biomarkers (N
      terminal-pro-brain natriuretic peptide (NT-pro-BNP) and troponin I), alone and in
      combination, for predicting right ventricular dysfunction (RVD) in patients with
      acute pulmonary embolism. 557 consecutive patients with suspected pulmonary
      embolism underwent pulmonary CT angiography. Patients with pulmonary embolism
      also underwent echocardiography and NT-pro-BNP/troponin I serum level
      measurements. Three different CT measurements were obtained (right ventricular
      (RV)/left ventricular (LV)(axial), RV/LV(4-CH) and RV/LV(volume)). CT
      measurements and NT-pro-BNP/troponin I serum levels were correlated with RVD at
      echocardiography. 77 patients with RVD showed significantly higher RV/LV ratios
      and NT-pro-BNP/troponin I levels compared to those without RVD (RV/LV(axial) 1.68
      +/- 0.84 versus 1.00 +/- 0.21; RV/LV(4-CH) 1.52 +/- 0.45 versus 1.01 +/- 0.21;
      RV/LV(volume) 1.97 +/- 0.53 versus 1.07 +/- 0.52; serum NT-pro-BNP 6,372 +/-
      2,319 versus 1,032 +/- 1,559 ng . L(-1); troponin I 0.18 +/- 0.41 versus 0.06 +/-
      0.18 g . L(-1)). The area under the curve for the detection of RVD of
      RV/LV(axial), RV/LV(4-CH), RV/LV(volume), NT-pro-BNP and troponin I were 0.84,
      0.87, 0.93, 0.83 and 0.70 respectively. The combination of biomarkers and
      RV/LV(volume) increased the AUC to 0.95 (RV/LV(volume) with NT-pro-BNP) and 0.93
      (RV/LV(volume) with troponin I). RV/LV(volume) is the most accurate CT parameter
      for identifying patients with RVD. A combination of RV/LV(volume) with NT-pro-BNP
      or troponin I measurements improves the diagnostic accuracy of either test alone.

PMID- 21965224
TI  - Molecular mechanisms of intensive care unit-acquired weakness.
AB  - Intensive care unit-acquired weakness (ICUAW) is an increasingly recognised and
      important clinical consequence of critical illness. It is associated with
      significant morbidity and mortality. The aetiology of this disease is not well
      understood. The purpose of this article is to review our understanding of the
      molecular pathogenesis of ICUAW in the context of current knowledge of clinical
      risk factors and aetiology. Key features of the disease are loss of muscle mass
      resulting from a shift in the dynamic balance of muscle protein synthesis and
      breakdown and a reduction in force-generating capacity. These alternations are
      secondary to neuropathy, disruption of the myofilament structure and function, a
      disrupted sarcoplasmic reticulum, electrical inexcitability and bioenergenetic
      failure. As knowledge and understanding of ICUAW grows, potential therapeutic
      targets will be identified, hopefully leading to multiple strategies for
      prevention and treatment of this important condition.

PMID- 21965225
TI  - Linezolid: an effective, safe and cheap drug for patients failing multidrug
      resistant tuberculosis treatment in India.
AB  - Linezolid is identified as an effective drug with which to treat patients failing
      multidrug-resistant (MDR)-tuberculosis (TB) treatment. However, cost and safety
      are the concerns. In India, the average price of a 600-mg pill of linezolid is
      less than one US dollar, much cheaper than most of the third-line drugs. A
      prospective study of 29 MDR-TB treatment failure patients (16 with laboratory
      proven extensively drug-resistant (XDR)-TB and the remaining 13 with MDR-TB with
      resistance to any quinolone but sensitive to injectables) was carried out in
      Delhi, India. All patients received daily unsupervised therapy with linezolid,
      one injectable agent, one fluoroquinolone and two or more other drugs. Patients
      received a median of six anti-mycobacterial agents. Besides linezolid,
      capreomycin, moxifloxacin, levofloxacin and amoxycillin-clavulanic acid were used
      in 41.4%, 58.6%, 41.4%, and 79.3% of patients. Out of a total of 29 patients,
      89.7% patients achieved sputum smear and culture conversion; 72.4% showed interim
      favourable outcome; 10.3% died, 6.8% failed and 10.3% patients defaulted.
      Linezolid had to be stopped in three (10.3%) patients due to adverse reactions.
      The outcome of treatment of 16 XDR-TB patients was comparable to the other 13 MDR
      TB patients. Linezolid is an effective, cheap and relatively safe drug for
      patients failing MDR-TB treatment, including those with confirmed XDR-TB.

PMID- 21965226
TI  - Physiological effects of roflumilast at rest and during exercise in COPD.
AB  - The purpose of this study was to investigate the effects of 500 MUg roflumilast,
      taken once daily for 12 weeks, on airway physiology during rest and exercise in
      patients with moderate-to-severe chronic obstructive pulmonary disease. This
      randomised, double-blind, placebo-controlled, parallel-group study was conducted
      in 250 patients with a post-bronchodilator forced expiratory volume in 1 s
      (FEV(1)) of 30-80% predicted and a functional residual capacity of >= 120% pred.
      Pre- and post-bronchodilator spirometry and body plethysmography, and pre
      bronchodilator constant work rate cycle exercise at 75% of peak work rate were
      evaluated. Exercise measurements included ventilation, breathing pattern,
      inspiratory capacity (IC) and arterial oxygen saturation measured by pulse
      oximetry (S(p,O(2))). Compared with placebo, 12 weeks of treatment with
      roflumilast was associated with: small but progressive increases in pre- and post
      bronchodilator FEV(1) and FEV(1)/forced vital capacity; small decreases in
      specific airway resistance; and no significant changes in resting vital capacity,
      IC or measurements of lung hyperinflation. There was no treatment effect on
      exercise endurance time. At a standardised exercise time after roflumilast,
      compared with placebo, IC increased by 0.12 L (p = 0.008) and S(p,O(2)) increased
      by 0.7% (p = 0.020); peak ventilation increased by 1.9 L . min(-1) (p = 0.014).
      Roflumilast treatment was associated with progressive improvement of airway
      function but not lung hyperinflation. Newly described non-bronchodilator effects
      of roflumilast included small but consistent improvements in air trapping and
      S(p,O(2)) during exercise.

PMID- 21965227
TI  - Increased incidence of nonfatal cardiovascular events in stroke patients with
      sleep apnoea: effect of CPAP treatment.
AB  - Obstructive sleep apnoea (OSA) is a risk factor for stroke, but little is known
      about the effect of OSA and continuous positive airway pressure (CPAP) on the
      incidence of long-term, nonfatal cardiovascular events (CVE) in stroke patients.
      A prospective observational study was made in 223 patients consecutively admitted
      for stroke. A sleep study was performed on 166 of them. 31 had an
      apnoea/hypopnoea index (AHI) <10 events . h(-1); 39 had an AHI between 10 and 19
      events . h(-1) and 96 had an AHI >= 20 events . h(-1). CPAP treatment was offered
      when AHI was >= 20 events . h(-1). Patients were followed up for 7 yrs and
      incident CVE data were recorded. The mean +/- SD age of the subjects was 73.3 +/-
      11 yrs; mean AHI was 26 +/- 16.7 events . h(-1). Patients with moderate-to-severe
      OSA who could not tolerate CPAP (AHI >= 20 events . h(-1); n = 68) showed an
      increased adjusted incidence of nonfatal CVE, especially new ischaemic strokes
      (hazard ratio 2.87, 95% CI 1.11-7.71; p = 0.03), compared with patients with
      moderate-to-severe OSA who tolerated CPAP (n = 28), patients with mild disease
      (AHI 10-19 events . h(-1); n = 36) and patients without OSA (AHI <10 events . h(
      1); n = 31). Our results suggest that the presence of moderate-to-severe OSA is
      associated with an increased long-term incidence of nonfatal CVE in stroke
      patients and that CPAP reduces the excess of incidence seen in these patients.

PMID- 21965228
TI  - Loss of polymeric immunoglobulin receptor expression is associated with lung
      tumourigenesis.
AB  - Polymeric immunoglobulin receptor (pIgR) expression is downregulated in lung
      cancer, but its implications in lung tumourigenesis remain unknown. We
      hypothesised that loss of pIgR expression occurs early, and is associated with
      cell proliferation and poor prognosis. pIgR expression was evaluated by
      immunohistochemistry in airways of patients with normal mucosa, pre-invasive
      lesions and invasive lesions, and correlated with clinical outcomes. 16-HBE and
      A549 cells stably transfected with pIgR were tested for proliferation, apoptosis
      and cell cycle progression. Immunostaining was strong in normal epithelium, but
      severely reduced in pre-invasive lesions and most lung cancers. Persistent
      expression was associated with younger age and adenocarcinoma subtype but not
      survival. pIgR overexpression significantly reduced A549 and 16-HBE
      proliferation. Growth inhibition was not due to cell cycle arrest, increased
      apoptosis or endoplasmic reticulum stress, but we observed altered expression of
      genes encoding for membrane proteins, including NOTCH3. Interestingly, NOTCH3
      expression was inversely correlated with pIgR expression in cell lines and
      tissues. pIgR expression was lost in most lung cancers and pre-invasive bronchial
      lesions, suggesting that pIgR downregulation is an early event in lung
      tumourigenesis. pIgR overexpression in A549 and 16-HBE cells inhibited
      proliferation. Future investigations are required to determine the mechanisms by
      which pIgR contributes to cell proliferation.

PMID- 21965230
TI  - FSA board advises against relaxing the ban on PAP in animal feed.

PMID- 21965229
TI  - Treatment failure in pneumonia: impact of antibiotic treatment and cost analysis.
AB  - The aim of this study was to investigate treatment failure (TF) in hospitalised
      community-acquired pneumonia (CAP) patients with regard to initial antibiotic
      treatment and economic impact. CAP patients were included in two open,
      prospective multicentre studies assessing the direct costs for in-patient
      treatment. Patients received treatment either with moxifloxacin (MFX) or a
      nonstandardised antibiotic therapy. Any change in antibiotic therapy after >72 h
      of treatment to a broadened antibiotic spectrum was considered as TF. Overall,
      1,236 patients (mean +/- SD age 69.6 +/- 16.8 yrs, 691 (55.9%) male) were
      included. TF occurred in 197 (15.9%) subjects and led to longer hospital stay
      (15.4 +/- 7.3 days versus 9.8 +/- 4.2 days; p < 0.001) and increased median
      treatment costs (?2,206 versus ?1,284; p<0.001). 596 (48.2%) patients received
      MFX and witnessed less TF (10.9% versus 20.6%; p < 0.001). After controlling for
      confounders in multivariate analysis, adjusted risk of TF was clearly reduced in
      MFX as compared with beta-lactam monotherapy (adjusted OR for MFX 0.43, 95% CI
      0.27-0.68) and was more comparable with a beta-lactam plus macrolide combination
      (BLM) (OR 0.68, 95% CI 0.38-1.21). In hospitalised CAP, TF is frequent and leads
      to prolonged hospital stay and increased treatment costs. Initial treatment with
      MFX or BLM is a possible strategy to prevent TF, and may thus reduce treatment
      costs.

PMID- 21965232
TI  - AHVLA confirms rationalisation of laboratory services.

PMID- 21965234
TI  - BVA President highlights concerns about surveillance.

PMID- 21965235
TI  - Vets and the Big Society.

PMID- 21965236
TI  - 'Paradigm has to change' to restore global influence.

PMID- 21965237
TI  - BSE: where are we now?

PMID- 21965239
TI  - Who or what is a veterinary specialist?

PMID- 21965240
TI  - FVE and AVMA issue joint statements on 'critical issues' for the profession.

PMID- 21965242
TI  - Epileptic brain damage in dogs and cats: myth or reality?

PMID- 21965243
TI  - Specialisation, self-assessment and measuring competency.

PMID- 21965244
TI  - Changes in the femoral head and/or neck in cats.

PMID- 21965245
TI  - Pharmacology and/or homeopathy.

PMID- 21965252
TI  - Dynamic assessment and its implications for RTI models.

PMID- 21965253
TI  - Dynamic testing, working memory, and reading comprehension growth in children
      with reading disabilities.
AB  - This longitudinal study assessed (a) whether performance changes in working
      memory (WM) as a function of dynamic testing were related to growth in reading
      comprehension and (b) whether WM performance among subgroups of children with
      reading disabilities (RD; children with RD only, children with both reading and
      arithmetic deficits, and low verbal IQ readers) varied as a function of dynamic
      testing. A battery of memory and reading measures was administered to 78 children
      (11.6 years) across three testing waves spaced 1 year apart. WM tasks were
      presented under initial and dynamic testing conditions (referred to as gain and
      maintenance testing). The important results were that (a) WM performance as a
      function of maintenance testing was a significant moderator of growth in reading
      comprehension and (b) WM performance of children with RD was statistically
      comparable within subgroups of RD but inferior to that of skilled readers across
      all testing conditions. The results support the notion that children's WM
      performance under dynamic testing conditions was related to the rate of growth in
      reading comprehension but unrelated to subgroup differences in reading.

PMID- 21965254
TI  - Making instruction and assessment responsive to diverse students' progress: group
      administered dynamic assessment in teaching mathematics.
AB  - This study entailed a 3 (instructional intervention) * 2 (assessment-type)
      between-subjects experimental design employing a pretest-intervention-posttest
      methodology. The instructional interventions were administered between subjects
      in three conditions: (a) dynamic instruction, (b) triarchic or theory of
      successful intelligence-control instruction, and (c) standard-control
      instruction. The assessment-type consisted between subjects of either (a) a group
      administered dynamic posttest or (b) the same group-administered posttest
      interspersed with a control filler activity. Performance in different mathematics
      content areas taught in fourth grade was investigated. In total, 1,332 students
      and 63 classroom teachers in 24 schools across six school districts participated
      in the study. The results indicate the advantages of using dynamic instruction
      and assessment in regular classrooms while teaching mathematics, especially when
      the student body is highly ethnically diverse.

PMID- 21965256
TI  - [Open partial nephrectomy. Personal technique and current outcomes. P. Russo.
      Editorial Comment].

PMID- 21965255
TI  - Open partial nephrectomy. Personal technique and current outcomes.
AB  - Modern imaging capabilities has created a renal tumor stage and size migration
      with approximately 70% of patients  today detected incidentally with a median
      tumor size of 4cm or less. In addition, our current understanding indicates  that
      renal cortical tumors are a family of neoplasms with distinct histopathological
      and cytogenetic features and  variable metastatic potential.The conventional
      clear cell tumor has a malignant potential and accounts for only 54%  of  the
      total renal cortical tumors but 90% of those that metastasize. Radical
      nephrectomy, whether performed by open or  minimally invasive surgical technique,
      plays an important role in the management of massive renal tumors that have 
      replaced the normal renal parenchyma, invade the the renal vein, and have
      associated regional lymphadenopathy or  metastatic disease. Partial nephrectomy
      has emerged as the treatment of choice for patients with smaller tumors.  This
      operation can be performed through a "miniflank" surgical incision without rib
      resection. Complications related  to partial nephrectomy, including bleeding,
      urinary fistula and infection occur in less than 10% of cases. Radical 
      nephrectomy should not be performed for the treatment of small renal tumors since
      it is associated with the causation  or worsening of preexisting CKD which can
      cause an increased likelihood of cardiovascular morbidity and mortality.  Despite
      a wealth of evidence supporting the more restricted indications for RN, strong
      evidence exists that it remains  over utilized in the United States. Widespread
      education and training in kidney preserving surgical strategies is  essential
      going forward.

PMID- 21965257
TI  - Genitourinary manifestations of sickle cell disease.
AB  - OBJECTIVES: Sickle cell disease is one of the most common hereditary diseases,
      and migration trends and cross breeding  have increased its incidence in Europe.
      While much has been published about the disease, there are few reviews in the 
      literature dealing with its manifestations in the genitourinary system. METHODS:
      We conducted a comprehensive review, using as our main instrument the PubMed
      online database, on recent advances  in knowledge of the pathophysiology and
      urological, nephrological, and andrological manifestations of the disease.
      RESULTS: Manifestations include sickle cell nephropathy, enuresis, nocturia,
      hematuria, priapism, renal medullary  carcinoma, and infarctions and necrosis in
      various organs of the genitourinary system. CONCLUSIONS: The characteristics of
      this important disease and the multisystemic spectrum it covers make knowledge of
      its genitourinary manifestations necessary.

PMID- 21965258
TI  - Infectious complications after transrectal ultrasound-guided prostatic biopsy.
      Analysis of our  experience.
AB  - OBJECTIVES: To establish the rate of infectious complications derived from the
      use of transrectal ultrasound-guided prostate biopsy (TRUS), identify its
      microbiological profile and related risk factors. METHODS: We designed a
      prospective non-randomized study in which we enrolled 220 patients undergoing
      TRUS biopsy at our centre between April and September 2008. The inclusion
      criteria were: suspicious digital rectal examination, PSA >10 ng/ml, and
      free/total ratio of PSA is assessed in patients with PSA 4-10 ng/ml. The
      exclusion criteria were: having an indwelling urinary catheter, the
      administration of antibiotic treatment in the week before the needle biopsy,
      manipulation of the urinary tract in the month prior to the needle biopsy,
      allergy to quinolones and risk of endocarditis, failure to comply with the
      antibiotic prophylaxis regimen and loss to follow-up. We analyzed the
      relationship between diabetes, immunodepression, previous UTI or prostatitis and
      positive prebiopsy urine culture with the appearance of fever, dysuria or
      bacteriuria following needle biopsy. RESULTS: Mean age was 69.5 years (+/-7.9),
      mean total PSA 12.7 ng/ml (+/-28.7), mean prostate volume 50.6 cc (+/-29.6) and
      mean number of cores obtained by needle biopsy 13.5 (+/-1.7). 25% of the patients
      had dysuria following needle biopsy, 3.2% fever and 4.5% bacteriuria. E.coli was
      the pathogen most frequently found in pre- and post-biopsy urine cultures. No
      statistically significant relationship was found between the appearance of
      dysuria and fever and being diabetic, having immunosuppression, previous UTI or
      prostatitis, prostate volume and number of cores obtained in the biopsy. Only the
      existence of a positive pre-biopsy urine culture and biopsy with more than 14
      cores proved to have a statistically significant association with the existence
      of bacteriuria following biopsy, p=0.007 and p= 0.018, respectively. CONCLUSIONS:
      Our rate of infectious complications was similar to that described in other
      series. The existence of a positive prebiopsy urine culture and obtaining more
      than 14 cores per biopsy was related, with statistical significance, to the
      existence of bacteriuria following the biopsy. E.coli was the most frequently
      isolated pathogen.

PMID- 21965259
TI  - Testicular tumors: residual retroperitoneal mass surgery after chemotherapy;Is it
      possible to predict their histology?
AB  - OBJECTIVES: We present our series of residual retroperitoneal mass surgery after
      chemotherapy. We evaluate possible preoperative parameters that can predict the
      retroperitoneal mass histology. Survival and relapse rates were also evaluated.
      METHODS: We reviewed sixty resections of residual retroperitoneal masses of
      testicular tumours after chemotherapy performed at our department between 1995
      and 2007. We evaluate the relationship between histology of the retroperitoneal
      mass and possible risk factors, such as outcomes after chemotherapy, which was
      evaluated as changes in the size of the retroperitoneal mass, and negativization
      of serum tumor markers. We also evaluate histology and size of the primary
      testicular cancer. RESULTS: The histology of retroperitoneal mass was necrosis or
      fibrosis in 25 (42%) cases, teratoma in 29 (48%) and viable tumor in 6 (10%). The
      size of the retroperitoneal mass decreased after the chemotherapy in 62% cases;
      moreover negative serum tumor markers were found in 87%. Elevated values of human
      chorionic gonadotropin were associated with viable cells in the retroperitoneal
      mass (p=0.014) and, the presence of teratoma in the primary tumor may be
      associated with teratoma in the retroperitoneal mass histology (p=0.002).
      However, no other preoperative factors that predict the residual mass histology
      were found. Repeated resections of retroperitoneal masses were required in four
      patients and 9 patients died during follow-up. CONCLUSIONS: We cannot determine
      preoperative parameters that accurately predict the histology of retroperitoneal
      masses. Therefore, resection of residual retroperitoneal masses after
      chemotherapy in non-seminomatous germ cell tumours must be performed.

PMID- 21965260
TI  - Complications of polypropylene mesh for the treatment of female pelvic floor
      disorders.
AB  - OBJECTIVES: To assess the complications of polypropylene mesh in the treatment of
      female pelvic floor disorders. METHODS: Retrospective study of patients with
      pelvic floor pathology (SUI, cystocele, rectocele, enterocele) undergoing pelvic
      floor intervention with surgical meshes from March 2002 to October 2009. We
      evaluated complications, effectiveness of the technique and distribution of the
      impact of the results. For statistical analysis SPSS software was used and the
      curve of impact was estimated by Cox model. RESULTS: We analyzed 363 patients. Of
      these 363 patients, 290 (79.9%) suffered from Stress Urinary Incontinence 37
      (10.2%)cystocele, 33 (9.4%) SUI and cystocele, 1 (0.3%) SUI and enterocele, 1
      (0.3%) cystocele and enterocele and 1 (0.3%) cystocele, enterocele and rectocele.
      The interventions done were: 34 (9.4%) anterior and middle compartment meshes, 1
      (0.3%) middle and posterior compartment meshes, 1 (0.3%) TOT and middle and
      posterior compartment mesh, 36 (9.9%) TVT and 3 (0.8%) TVT and anterior and
      middle compartment mesh. The median follow-up was 36 (3-90) months. 50 patients
      (13.8%) presented complications: 21 (42%) had lower urinary tract irritative
      symptoms, 10 (20%) externalization of the mesh, 3 (6%) necrotizing fascitis, 3
      (6%)obturator fossa, thigh root or vaginal abscess, 5 (10%) chronic pelvic pain,
      thigh pain or dyspareunia, 2 (4%) bruising and bleeding, 3 (6%) urinary tract
      infections, 1 (2%)mesh entering bladder and 2 (4%) obstructive symptoms. The
      procedures were effective in 350 (96.4%)patients. The impact of complications was
      manifested in the first 10 months after surgery. CONCLUSIONS: Polypropylene
      meshes are very effective in the treatment of female pelvic floor disorders.
      Approximately 10% of the patients had complications that resolved spontaneously
      or with medical treatment in most cases. One third of the complications are
      subsidiaries of surgery, by removing the mesh totaly or partialy, without
      affecting the intervention results.

PMID- 21965261
TI  - Calcified renal artery aneurism embolization in a solitary kidney.
AB  - OBJECTIVE: To review presentation, diagnosis and treatment of renal artery
      aneurysms, a very uncommon disease. METHODS: We report the case of a male with a
      calcified renal artery aneurysm in a solitary kidney. RESULTS: Symptomatic
      effects may be hypertension, hematuria or flank pain. Arteriosclerosis and medial
      dysplasia are the most frequent causes and diagnosis is based on CT scan and
      angiography. CONCLUSIONS: The renal artery aneurysm is a disease with low
      prevalence and there is no clear protocol for management. The number of cases has
      increased over the last decades and endovasculrar treatment is a good therapeutic
      option.

PMID- 21965262
TI  - Prostatic leiomyoma. Case report.
AB  - OBJECTIVE: We try to show the relevance of this rare pathology and to set its
      importance in the differential diagnosis  of prostate masses. METHODS: We report
      a case and perform a search in the MEDLINE database of the series described up to
      the date. RESULTS: Prostatic leiomyoma is a extremely rare anatomopathological
      finding, though the appearance of a glandular  hyperplasia with small areas of
      leiomyomatous growth is more common. Up to date there are just a hundred cases
      described. They are benign mesenchymal tumors without evidence of disease
      recurrence after surgery. When they present symptomatology, they emulate benign
      hyperplasia with urinary tract infections. Although it has  benign nature,
      surgical intervention is indicated when severe clinical symptoms appear.
      CONCLUSIONS: The recognition of this benign entity and the distinction from other
      neoplasias has important therapeutic  and prognostic implications. Imaging
      techniques and pathological analysis are crucial for this reason. When an unusual
      prostatic mass is detected, the leiomyoma must be included in the differential
      diagnosis.

PMID- 21965263
TI  - Primary renal Ewing's sarcoma.
AB  - OBJECTIVE: To report two new cases of Ewing's sarcoma/primitive neuroectodermal
      tumor of the kidney, one of  them with tumor thrombus in cava. METHOD:
      Characterization of two new cases and literature review by PubMed search.
      RESULTS: We report the cases of two men diagnosed with primary renal Ewing's
      sarcoma, who have been treated  with nephrectomy and adjuvant chemotherapy, being
      in complete remission to date. CONCLUSION: Ewing's sarcoma / primitive
      neuroectodermal tumor of the kidney is a rare condition that mainly  affects
      young adults. The natural history of these tumors is the evolution towards
      metastatic disease and death.  Treatment is multimodal, combining surgery and
      chemotherapy. The role of radiotherapy is not well established.

PMID- 21965264
TI  - Renal pelvis spontaneous rupture secondary to ureteral lithiasis. Case report and
      bibliographic  review.
AB  - OBJECTIVE: To report a case seen at the Urology Department and comment on the
      literature. METHODS: We present the case of 46 year-old male who presented left
      flank pain. Intravenous pyelography was  performed.  The study showed evidence of
      contrast extravasation at the level of the left renal pelvis and a 7 mm stone
      located on  the left ureterovesical junction. A literature search was performed
      using Promedicum, Pub Med and Ovid. The search words  were: rupture, renal
      pelvis, lithiasis and spontaneous combined by boolean operators. RESULTS: The
      management was successful using endourology procedures and a double pigtail
      catheter for a two week period. CONCLUSIONS: Spontaneous rupture of the renal
      pelvis (SRRP) is an infrequent pathological event. Most of the  cases are 
      related to obstructive uropathy, infection and diagnostic procedures. Intravenous
      pyelography is a useful tool although  intravenous contrast CT scan has higher
      sensibility. The treatment depends on patient state but most cases can be managed
      with minimally invasive procedures and double pigtail catheter placement.

PMID- 21965265
TI  - Bladder foreign body.

PMID- 21965266
TI  - Complex renal cyst.

PMID- 21965268
TI  - Elevated LET components in clinical proton beams.
AB  - This paper assesses the contribution of secondary particles to pencil and
      passively scattered proton beams, in particular when considering the dose
      averaged linear energy transfer (LET(d)) in biological treatment planning. Proton
      Monte Carlo simulations are performed in water phantoms and for two patients,
      considering all primary and secondary particles, including recoils from inelastic
      nuclear interactions. Our results show that secondary protons exhibit LET(d)
      values up to a factor 10 higher than those of the primary protons at the same
      depth. Thus, secondary protons have a significant impact on the LET(d). Their
      contribution increases the LET(d) by ~50% along the central axis and even >200%
      in the penumbra. Furthermore, the LET maximum after the peak changes from 12 to
      15 keV um(-1) when adding secondary protons to the primary contribution. This is
      important when modeling LET(d) with analytical methods. The contribution of
      recoils (A > 3) is observed to be 1.2% in the entrance region considering a
      prostate case. The degree of biological damage inflicted by recoils remains hard
      to quantify, but is discussed on the basis of detailed energy spectra. The
      results highlight the role of secondary protons in LET-based radiobiological
      effectiveness calculations for proton therapy and when analyzing radiobiological
      experiments. Furthermore, the findings demonstrate the impact of inhomogeneities
      on the LET and the subtle changes between the LET distributions of passively
      scattered and actively scanned beams.

PMID- 21965269
TI  - Study of intensity-modulated photon-electron radiation therapy using digital
      phantoms.
AB  - Intensity-modulated photon-electron radiation therapy (IMPERT) takes advantage of
      the high conformity of photon intensity-modulated radiation therapy (IMRT) and
      low distal dose of electrons to reduce the total energy delivered to healthy
      tissue, potentially reducing serious side effects including secondary
      malignancies. This theoretical study was undertaken to elucidate basic principles
      of IMPERT planning and to help quantify the advantage of IMPERT over photon IMRT.
      Plans using 6 MV x-rays alone (IMRT) or in combination with 6-21 MeV electron
      beams (IMPERT) were developed for digital cylindrical water phantoms that
      included an organ at risk (OAR) situated 0.25 cm below a 5 cm thick planning
      target volume (PTV), with the top of the PTV positioned up to 4 cm below the
      surface. Electron beam energy and percentage dose contribution of the electron
      beam to the total dose were investigated with a flat-bottom PTV. The effect of
      target shape was investigated with a concave- or convex-bottom PTV positioned at
      the surface. Air or bone cavities were embedded in the PTV to investigate the
      effect of tissue inhomogeneity. Dose variations in the electron dose distribution
      due to tissue inhomogeneity were accurately calculated with Monte Carlo
      simulation. The preferred electron dose contribution was approximately 50% of the
      total dose. For all the PTV-OAR scenarios, IMPERT was able to achieve comparable
      PTV coverage and OAR sparing as IMRT while reducing the energy deposited to the
      healthy tissue by 6-25%. The IMPERT technique is a clinically viable approach for
      reducing serious side effects in radiotherapy.

PMID- 21965270
TI  - Downregulation of alpha-fetoprotein expression by LHX4: a critical role in
      hepatocarcinogenesis.
AB  - LHX4 is a member of the LIM-homeobox family and plays a critical role in
      pituitary development and differentiation. Several lines of evidences have
      reported their aberrant expression in cancers. However, the exact roles of LHX4
      in carcinogenesis remain unclear. In this study, LHX4 expression was analyzed in
      tumor and paired non-tumor tissues obtained from patients with hepatocellular
      carcinoma (HCC) using western blotting and immunohistochemistry. LHX4 was found
      to be downregulated in tumor tissues and negatively correlated with
      differentiation grade and alpha-fetoprotein (AFP) levels in 66 HCC patients. To
      clarify the biological functions of LHX4, transient or stable transfectants
      overexpressing LHX4 were generated in human hepatoma cells (Huh7 and HepG2). LHX4
      overexpression in Huh7 and HepG2 cells induced a more differentiated phenotype by
      reducing AFP expression. Using in silico analysis, the evolutionary conserved
      region within the AFP promoter containing LHX4-binding site was identified,
      implying that AFP is a putative target for LHX4. Moreover, ectopic LHX4
      overexpression attenuated Huh7 and HepG2 proliferation. Importantly, the growth
      inhibitory effect of LHX4 was reversed by replenishing AFP to the LHX4
      overexpressing cells, providing a functional relevance between LHX4 and AFP.
      Finally, we analyzed expressions of LHX4 and AFP during normal liver development.
      Hepatic LHX4 expression increased in adult liver in a manner that parallel AFP
      repression. In conclusion, these data indicate that LHX4 may act as a potential
      tumor suppressor in hepatocarcinogenesis, suggesting that targeting LHX4 to
      downregulate AFP might have therapeutic implications.

PMID- 21965271
TI  - Graded activation of the MEK1/MT1-MMP axis determines renal epithelial cell tumor
      phenotype.
AB  - Activation of Raf/Ras/mitogen-activated protein kinase (MEK)/mitogen-activated
      protein kinase signaling and elevated expression of membrane type-1 matrix
      metalloproteinase (MT1-MMP) are associated with von Hippel-Lindau gene
      alterations in renal cell carcinoma. We postulated that the degree of MEK
      activation was related to graded expression of MT1-MMP and the resultant
      phenotype of renal epithelial tumors. Madin Darby canine kidney epithelial cells
      transfected with a MEK1 expression plasmid yielded populations with morphologic
      phenotypes ranging from epithelial, mixed epithelial/mesenchymal to mesenchymal.
      Clones were analyzed for MEK1 activity, MT1-MMP expression and extent of
      epithelial-mesenchymal transition. Phenotypes of the MDCK-MEK1 clones were
      evaluated in vivo with nu/nu mice. Tissue microarray of renal cell cancers was
      quantitatively assessed for expression of phosphorylated MEK1 and MT1-MMP
      proteins and correlations drawn to Fuhrman nuclear grade. Graded increases in the
      MEK signaling module were associated with graded induction of epithelial
      mesenchymal transition of the MDCK cells and induction of MT1-MMP transcription
      and synthesis. Inhibition of MEK1 and MT1-MMP activity reversed the epithelial
      mesenchymal transition. Tumors generated by epithelial, mixed
      epithelial/mesenchymal and mesenchymal MDCK clones demonstrated a gradient of
      phenotypes extending from well-differentiated, fully encapsulated non-invasive
      tumors to tumors with an anaplastic morphology, high Fuhrman nuclear score,
      neoangiogenesis and invasion. Tumor microarray demonstrated a statistically
      significant association between the extent of phosphorylated MEK1, MT1-MMP
      expression and nuclear grade. We conclude that graded increases in the MEK1
      signaling module are correlated with M1-MMP expression, renal epithelial cell
      tumor phenotype, invasive activity and nuclear grade. Phosphorylated MEK1 and MT1
      MMP may represent novel, and mechanistic, biomarkers for the assessment of renal
      cell carcinoma.

PMID- 21965272
TI  - Common genetic variants in cell cycle pathway are associated with survival in
      stage III-IV non-small-cell lung cancer.
AB  - Cell cycle progression contributes to the cellular response to DNA-damaging
      factors, such as chemotherapy and radiation. We hypothesized that the genetic
      variations in cell cycle pathway genes may modulate treatment responses and
      affect survival in patients with advanced non-small-cell lung cancer (NSCLC). We
      genotyped 374 single-nucleotide polymorphisms (SNPs) from 49 cell cycle-related
      genes in 598 patients with stages III-IV NSCLC treated with first-line platinum
      based chemotherapy with/without radiation. We analyzed the individual and
      combined associations of these SNPs with survival and evaluated their gene-gene
      interactions using survival tree analysis. In the analysis of survival in all the
      patients, 39 SNPs reached nominal significance (P < 0.05) and 4 SNPs were
      significant at P <0.01. However, none of these SNPs remained significant after
      correction for multiple comparisons at a false discovery rate of 10%. In
      stratified analysis by treatment modality, after adjusting for multiple
      comparisons, nine SNPs in chemotherapy alone and one SNP in chemoradiation
      remained significant. The most significant SNP in chemotherapy group was
      CCNB2:rs1486878 [hazard ratio (HR) = 1.69, 95% confidence interval (CI), 1.25
      2.30, P = 0.001]. TP73: rs3765701 was the only significant SNP in chemoradiation
      group (HR = 1.87; 95% CI = 1.35-2.59, P = 1.8 * 10(-4)). In cumulative analysis,
      we found a significant gene-dosage effect in patients receiving chemotherapy
      alone. Survival tree analysis demonstrated potential higher order gene-gene and
      gene-treatment interactions, which could be used to predict survival status based
      on distinct genetic signatures. These results suggest that genetic variations in
      cell cycle pathway genes may affect the survival of patients with stages III-IV
      NSCLC individually and jointly.

PMID- 21965273
TI  - Green tea polyphenol EGCG suppresses lung cancer cell growth through upregulating
      miR-210 expression caused by stabilizing HIF-1alpha.
AB  - (-)-Epigallocatechin-3-gallate (EGCG) has been reported to affect many cellular
      regulatory pathways. This study aims to determine whether EGCG could target
      microRNA (miRNA), one of the mechanisms for cells to achieve subtle change in
      multiple targets. We found that, in both human and mouse lung cancer cells in
      culture, EGCG specifically upregulated the expression of miR-210, a major miRNA
      regulated by HIF-1alpha. Furthermore, we found that overexpression of miR-210 led
      to reduced cell proliferation rate and anchorage-independent growth as well as
      reduced sensitivity to EGCG. On the mechanisms of miR-210 regulation by EGCG, we
      demonstrated that the regulation was mediated through the hypoxia-response
      element in miR-210 promoter. Consistently, the upregulation of miR-210 was found
      to be correlated with the stabilized HIF-1alpha in lung cancer cell lines after
      EGCG treatment. This EGCG-induced stabilization of HIF-1alpha was further shown
      by the stabilization of HA-tagged HIF-1alpha but not the P402A/P564A-mutated HIF
      1alpha by EGCG, suggesting that EGCG targets the oxygen-dependent degradation
      (ODD) domain. Direct evidence was obtained by affinity binding assay showing that
      EGCG specifically binds HIF-1alpha with a K(d) = 3.47 MUM. This result suggests
      that EGCG binding interferes with the hydroxylation of key Pro residues in the
      ODD domain, preventing HIF-1alpha from the Pro hydroxylation-dependent
      ubiquitination and subsequent proteosome-mediated degradation. In summary, our
      results demonstrated, for the first time, the elevation of miR-210 by EGCG in
      lung cancer cell lines and this is mediated by the stabilization of HIF-1alpha.
      This event contributes to the anticancer activity of EGCG.

PMID- 21965275
TI  - Performance studies of four-dimensional cone beam computed tomography.
AB  - Four-dimensional cone beam computed tomography (4DCBCT) has been proposed to
      characterize the breathing motion of tumors before radiotherapy treatment.
      However, when the acquired cone beam projection data are retrospectively gated
      into several respiratory phases, the available data to reconstruct each phase is
      under-sampled and thus causes streaking artifacts in the reconstructed images. To
      solve the under-sampling problem and improve image quality in 4DCBCT, various
      methods have been developed. This paper presents performance studies of three
      different 4DCBCT methods based on different reconstruction algorithms. The aims
      of this paper are to study (1) the relationship between the accuracy of the
      extracted motion trajectories and the data acquisition time of a 4DCBCT scan and
      (2) the relationship between the accuracy of the extracted motion trajectories
      and the number of phase bins used to sort projection data. These aims will be
      applied to three different 4DCBCT methods: conventional filtered backprojection
      reconstruction (FBP), FBP with McKinnon-Bates correction (MB) and prior image
      constrained compressed sensing (PICCS) reconstruction. A hybrid phantom
      consisting of realistic chest anatomy and a moving elliptical object with known
      3D motion trajectories was constructed by superimposing the analytical projection
      data of the moving object to the simulated projection data from a chest CT volume
      dataset. CBCT scans with gantry rotation times from 1 to 4 min were simulated,
      and the generated projection data were sorted into 5, 10 and 20 phase bins before
      different methods were used to reconstruct 4D images. The motion trajectories of
      the moving object were extracted using a fast free-form deformable registration
      algorithm. The root mean square errors (RMSE) of the extracted motion
      trajectories were evaluated for all simulated cases to quantitatively study the
      performance. The results demonstrate (1) longer acquisition times result in more
      accurate motion delineation for each method; (2) ten or more phase bins are
      necessary in 4DCBCT to ensure sufficient temporal resolution in tumor motion and
      (3) to achieve the same performance as FBP-4DCBCT with a 4 min data acquisition
      time, MB-4DCBCT and PICCS-4DCBCT need about 2- and 1 min data acquisition times,
      respectively.

PMID- 21965276
TI  - High-sensitivity C-reactive protein is not a good indicator of infection in
      patients with systemic lupus erythematosus.

PMID- 21965278
TI  - The link of HLA-B27 with interleukin-23/interleukin-17 axis in coexisting
      systemic lupus erythematosus and ankylosing spondylitis.

PMID- 21965277
TI  - Giant disseminated condylomatosis in SLE.
AB  - INTRODUCTION: Females with systemic lupus erythematosus (SLE) have higher
      prevalence of human papillomavirus (HPV) infection, which can lead to the
      development of warts. Herein we report the first case of giant disseminated
      condylomatosis (GDC) in a SLE female on mycophenolate mofetil (MMF). CASE REPORT:
      The patient, a 33-year-old, Black female, was diagnosed with SLE during her first
      pregnancy in 2003 based on the features of arthritis, skin rash, seizures,
      nephritis and presence of antinuclear antibodies. Her pregnancy resulted in
      preterm delivery of a stillborn fetus at 28 weeks. Since that time she has been
      treated with steroids and different regimens of immunosuppressive drugs such as
      cyclophosphamide, azathioprine and lately MMF. In the last few years she
      presented GDC involving the genital area in addition to skin on the lower
      abdomen. Topical therapy with trichloroacetic acid, imiquimod and podophyllin was
      only partially effective. Different types of HPV were identified in the lesions,
      being HPV-11 in abdomen, HPV 6, 11, 42 in vulva, HPV-6, 11 in vagina and HPV-6,
      11 in endocervix. CONCLUSIONS: GDC may be a complication of SLE, secondary to the
      disease itself, its treatment or other factors not yet identified.

PMID- 21965274
TI  - Breast cancer susceptibility polymorphisms and endometrial cancer risk: a
      Collaborative Endometrial Cancer Study.
AB  - Recent large--scale association studies, both of genome-wide and candidate gene
      design, have revealed several single-nucleotide polymorphisms (SNPs) which are
      significantly associated with risk of developing breast cancer. As both breast
      and endometrial cancers are considered to be hormonally driven and share multiple
      risk factors, we investigated whether breast cancer risk alleles are also
      associated with endometrial cancer risk. We genotyped nine breast cancer risk
      SNPs in up to 4188 endometrial cases and 11,928 controls, from between three and
      seven Caucasian populations. None of the tested SNPs showed significant evidence
      of association with risk of endometrial cancer.

PMID- 21965279
TI  - Subacute cerebellar ataxia and atrophy developed in a young woman with systemic
      lupus erythematosus whose cerebrospinal fluid was positive for antineuronal cell
      antibody.
AB  - Subacute cerebellar ataxia in combination with cerebellar atrophy has rarely been
      reported as one of the manifestations of lupus in the central nervous system
      (CNS). We describe a 27-year-old woman with systemic lupus erythematosus who
      developed subacute cerebellar ataxia. Computed tomography and magnetic resonance
      imaging of her brain showed cerebellar atrophy in both hemispheres, particularly
      on the right side. Moreover, increased antineuronal cell antibody levels were
      detected in her cerebrospinal fluid. The cerebellar ataxia improved markedly
      following high-dose corticosteroid administration. This suggests that a
      relationship exists between autoantibodies and subacute atrophic processes in CNS
      lupus.

PMID- 21965280
TI  - Olanzapine-induced neutropenia in a patient with systemiclupus erythematosus: a
      role of FcgammaRIIIb polymorphism?
AB  - In this study, we report the case of a Chinese patient with systemic lupus
      erythematosus (SLE) who developed neutropenia after treatment by olanzapine for
      the SLE-related psychiatric symptoms. The relationship between agranulocytosis,
      SLE and olanzapine is still unknown. Fcgamma receptor IIIb (FcgammaRIIIb) is a
      low-affinity receptor, constitutively expressed only by neutrophils; NA1 and NA2
      have been identified as representing polymorphisms of FcgammaRIIIb. NA1 is
      associated with the incidence of autoimmune neutropenia and is particularly
      frequent in Asiatic ethnic groups. The Chinese patient resulted to be homozygous
      for NA1. We suggest that the presence of NA1 allele may be a predisposing factor
      to olanzapine-induced agranulocytosis in patients with SLE. Hence, the analysis
      of FcgammaRIIIb polymorphism should be investigated in other cases of
      antipsychotic-induced agranulocytosis.

PMID- 21965281
TI  - Direct impact analysis of multi-leaf collimator leaf position errors on dose
      distributions in volumetric modulated arc therapy: a pass rate calculation
      between measured planar doses with and without the position errors.
AB  - We propose a new method for analyzing the direct impact of multi-leaf collimator
      (MLC) leaf position errors on dose distributions in volumetric modulated arc
      therapy (VMAT). The technique makes use of the following processes. Systematic
      leaf position errors are generated by directly changing a leaf offset in a linac
      controller; dose distributions are measured by a two-dimensional diode array;
      pass rates of the dose difference between measured planar doses with and without
      the position errors are calculated as a function of the leaf position error.
      Three different treatment planning systems (TPSs) were employed to create VMAT
      plans for five prostate cancer cases and the pass rates were compared between the
      TPSs under various leaf position errors. The impact of the leaf position errors
      on dose distributions depended upon the final optimization result from each TPS,
      which was explained by the correlation between the dose error and the average
      leaf gap width. The presented method determines leaf position tolerances for VMAT
      delivery for each TPS, which may facilitate establishing a VMAT quality assurance
      program in a radiotherapy facility.

PMID- 21965282
TI  - Whole slide images and digital media in pathology education, testing, and
      practice: the Oklahoma experience.
AB  - Examination of glass slides is of paramount importance in pathology training.
      Until the introduction of digitized whole slide images that could be accessed
      through computer networks, the sharing of pathology slides was a major logistic
      issue in pathology education and practice. With the help of whole slide images,
      our department has developed several online pathology education websites. Based
      on a modular architecture, this program provides online access to whole slide
      images, still images, case studies, quizzes and didactic text at different
      levels. Together with traditional lectures and hands-on experiences, it forms the
      back bone of our histology and pathology education system for residents and
      medical students. The use of digitized whole slide images has a.lso greatly
      improved the communication between clinicians and pathologist in our institute.

PMID- 21965283
TI  - Mitotic figure recognition: agreement among pathologists and computerized
      detector.
AB  - Despite the prognostic importance of mitotic count as one of the components of
      the Bloom-Richardson grade, several studies have found that pathologists'
      agreement on the mitotic grade is fairly modest. Collecting a set of more than
      4,200 candidate mitotic figures, we evaluate pathologists' agreement on
      individual figures, and train a computerized system for mitosis detection,
      comparing its performance to the classifications of three pathologists. The
      system's and the pathologists' classifications are based on evaluation of digital
      micrographs of hematoxylin and eosin stained breast tissue. On figures where the
      majority of pathologists agree on a classification, we compare the performance of
      the trained system to that of the individual pathologists. We find that the level
      of agreement of the pathologists ranges from slight to moderate, with strong
      biases, and that the system performs competitively in rating the ground truth
      set. This study is a step towards automatic mitosis count to accelerate a
      pathologist's work and improve reproducibility.

PMID- 21965284
TI  - Subunit organization in the Dam1 kinetochore complex and its ring around
      microtubules.
AB  - All eukaryotic cells must segregate their chromosomes equally between two
      daughter cells at each division. This process needs to be robust, as errors in
      the form of loss or gain of genetic material have catastrophic effects on
      viability. Chromosomes are captured, aligned, and segregated to daughter cells
      via interaction with spindle microtubules mediated by the kinetochore. In
      Saccharomyces cerevisiae one microtubule attaches to each kinetochore, requiring
      extreme processivity from this single connection. The yeast Dam1 complex, an
      essential component of the outer kinetochore, forms rings around microtubules and
      in vitro recapitulates much of the functionality of a kinetochore-microtubule
      attachment. To understand the mechanism of the Dam1 complex at the kinetochore,
      we must know how it binds to microtubules, how it assembles into rings, and how
      assembly is regulated. We used electron microscopy to map several subunits within
      the structure of the Dam1 complex and identify the organization of Dam1 complexes
      within the ring. Of importance, new data strongly support a more passive role for
      the microtubule in Dam1 ring formation. Integrating this information with
      previously published data, we generated a structural model for the Dam1 complex
      assembly that advances our understanding of its function and will direct future
      experiments.

PMID- 21965285
TI  - The actin nucleation factor JMY is a negative regulator of neuritogenesis.
AB  - Junction-mediating and regulatory protein (JMY) is a p53 cofactor that was
      recently shown to nucleate actin assembly by a hybrid mechanism involving tandem
      actin monomer binding and Arp2/3 complex activation. However, the regulation and
      function of JMY remain largely uncharacterized. We examined the activity of JMY
      in vitro and in cells, its subcellular distribution, and its function in
      fibroblast and neuronal cell lines. We demonstrated that recombinant full-length
      JMY and its isolated WASP homology 2 domain, connector, and acidic region (WWWCA)
      have potent actin-nucleating and Arp2/3-activating abilities in vitro. In
      contrast, the activity of full-length JMY, but not the isolated WWWCA domain, is
      suppressed in cells. The WWWCA domain is sufficient to promote actin-based bead
      motility in cytoplasmic extracts, and this activity depends on its ability to
      activate the Arp2/3 complex. JMY is expressed at high levels in brain tissue, and
      in various cell lines JMY is predominantly cytoplasmic, with a minor fraction in
      the nucleus. Of interest, silencing JMY expression in neuronal cells results in a
      significant enhancement of the ability of these cells to form neurites,
      suggesting that JMY functions to suppress neurite formation. This function of JMY
      requires its actin-nucleating activity. These findings highlight a previously
      unrecognized function for JMY as a modulator of neuritogenesis.

PMID- 21965286
TI  - p31(comet) acts to ensure timely spindle checkpoint silencing subsequent to
      kinetochore attachment.
AB  - The spindle assembly checkpoint links the onset of anaphase to completion of
      chromosome-microtubule attachment and is mediated by the binding of Mad and Bub
      proteins to kinetochores of unattached or maloriented chromosomes. Mad2 and BubR1
      traffic between kinetochores and the cytosol, thereby transmitting a "wait
      anaphase" signal to the anaphase-promoting complex. It is generally assumed that
      this signal dissipates automatically upon kinetochore-microtubule binding, but it
      has been shown that under conditions of nocodazole-induced arrest p31(comet), a
      Mad2-binding protein, is required for mitotic progression. In this article we
      investigate the localization and function of p31(comet) during normal,
      unperturbed mitosis in human and marsupial cells. We find that, like Mad2,
      p31(comet) traffics on and off kinetochores and is also present in the cytosol.
      Cells depleted of p31(comet) arrest in metaphase with mature bipolar kinetochore
      microtubule attachments, a satisfied checkpoint, and high cyclin B levels. Thus
      p31(comet) is required for timely mitotic exit. We propose that p31(comet) is an
      essential component of the machinery that silences the checkpoint during each
      cell cycle.

PMID- 21965287
TI  - ALBA proteins are stage regulated during trypanosome development in the tsetse
      fly and participate in differentiation.
AB  - The protozoan parasite Trypanosoma brucei is responsible for sleeping sickness
      and alternates between mammal and tsetse fly hosts, where it has to adapt to
      different environments. We investigated the role of two members of the ALBA
      family, which encodes hypothetical RNA-binding proteins conserved in most
      eukaryotes. We show that ALBA3/4 proteins colocalize with the DHH1 RNA-binding
      protein and with a subset of poly(A+) RNA in stress granules upon starvation.
      Depletion of ALBA3/4 proteins by RNA interference in the cultured procyclic stage
      produces cell modifications mimicking several morphogenetic aspects of
      trypanosome differentiation that usually take place in the fly midgut. A
      combination of immunofluorescence data and videomicroscopy analysis of live
      trypanosomes expressing endogenously ALBA fused with fluorescent proteins
      revealed that ALBA3/4 are present throughout the development of the parasite in
      the tsetse fly, with the striking exception of the transition stages found in the
      proventriculus region. This involves migration of the nucleus toward the
      posterior end of the cell, a phenomenon that is perturbed upon forced expression
      of ALBA3 during the differentiation process, showing for the first time the
      involvement of an RNA-binding protein in trypanosome development in vivo.

PMID- 21965288
TI  - beta-catenin and Smad3 regulate the activity and stability of myocardin-related
      transcription factor during epithelial-myofibroblast transition.
AB  - Injury to the adherens junctions (AJs) synergizes with transforming growth factor
      beta1 (TGFbeta) to activate a myogenic program (alpha-smooth muscle actin [SMA]
      expression) in the epithelium during epithelial-myofibroblast transition (EMyT).
      Although this synergy plays a key role in organ fibrosis, the underlying
      mechanisms have not been fully defined. Because we recently showed that Smad3
      inhibits myocardin-related transcription factor (MRTF), the driver of the SMA
      promoter and many other CC(A/T)-rich GG element (CArG) box-dependent cytoskeletal
      genes, we asked whether AJ components might affect SMA expression through
      interfering with Smad3. We demonstrate that E-cadherin down-regulation
      potentiates, whereas beta-catenin knockdown inhibits, SMA expression. Contact
      injury and TGFbeta enhance the binding of beta-catenin to Smad3, and this
      interaction facilitates MRTF signaling by two novel mechanisms. First, it
      inhibits the Smad3/MRTF association and thereby allows the binding of MRTF to its
      myogenic partner, serum response factor (SRF). Accordingly, beta-catenin down
      regulation disrupts the SRF/MRTF complex. Second, beta-catenin maintains the
      stability of MRTF by suppressing the Smad3-mediated recruitment of glycogen
      synthase kinase-3beta to MRTF, an event that otherwise leads to MRTF
      ubiquitination and degradation and the consequent loss of SRF/MRTF-dependent
      proteins. Thus beta-catenin controls MRTF-dependent transcription and emerges as
      a critical regulator of an array of cytoskeletal genes, the "CArGome."

PMID- 21965289
TI  - Nsk1 ensures accurate chromosome segregation by promoting association of
      kinetochores to spindle poles during anaphase B.
AB  - Type 1 phosphatase (PP1) antagonizes Aurora B kinase to stabilize kinetochore
      microtubule attachments and to silence the spindle checkpoint. We screened for
      factors that exacerbate the growth defect of Deltadis2 cells, which lack one of
      two catalytic subunits of PP1 in fission yeast, and identified Nsk1, a novel
      protein required for accurate chromosome segregation. During interphase, Nsk1
      resides in the nucleolus but spreads throughout the nucleoplasm as cells enter
      mitosis. Following dephosphorylation by Clp1 (Cdc14-like) phosphatase and at
      least one other phosphatase, Nsk1 localizes to the interface between kinetochores
      and the inner face of the spindle pole body during anaphase. In the absence of
      Nsk1, some kinetochores become detached from spindle poles during anaphase B. If
      this occurs late in anaphase B, then the sister chromatids of unclustered
      kinetochores segregate to the correct daughter cell. These unclustered
      kinetochores are efficiently captured, retrieved, bioriented, and segregated
      during the following mitosis, as long as Dis2 is present. However, if
      kinetochores are detached from a spindle pole early in anaphase B, then these
      sister chromatids become missegregated. These data suggest Nsk1 ensures accurate
      chromosome segregation by promoting the tethering of kinetochores to spindle
      poles during anaphase B.

PMID- 21965290
TI  - Fast-acting and nearly gratuitous induction of gene expression and protein
      depletion in Saccharomyces cerevisiae.
AB  - We describe the development and characterization of a system that allows the
      rapid and specific induction of individual genes in the yeast Saccharomyces
      cerevisiae without changes in nutrients or temperature. The system is based on
      the chimeric transcriptional activator Gal4dbd.ER.VP16 (GEV). Upon addition of
      the hormone beta-estradiol, cytoplasmic GEV localizes to the nucleus and binds to
      promoters containing Gal4p consensus binding sequences to activate transcription.
      With galactokinase Gal1p and transcriptional activator Gal4p absent, the system
      is fast-acting, resulting in readily detectable transcription within 5 min after
      addition of the inducer. beta-Estradiol is nearly a gratuitous inducer, as
      indicated by genome-wide profiling that shows unintended induction (by GEV) of
      only a few dozen genes. Response to inducer is graded: intermediate
      concentrations of inducer result in production of intermediate levels of product
      protein in all cells. We present data illustrating several applications of this
      system, including a modification of the regulated degron method, which allows
      rapid and specific degradation of a specific protein upon addition of beta
      estradiol. These gene induction and protein degradation systems provide important
      tools for studying the dynamics and functional relationships of genes and their
      respective regulatory networks.

PMID- 21965292
TI  - The endocytic protein GRAF1 is directed to cell-matrix adhesion sites and
      regulates cell spreading.
AB  - The rho GTPase-activating protein GTPase regulator associated with focal adhesion
      kinase-1 (GRAF1) remodels membranes into tubulovesicular clathrin-independent
      carriers (CLICs) mediating lipid-anchored receptor endocytosis. However, the cell
      biological functions of this highly prevalent endocytic pathway are unclear. In
      this article, we present biochemical and cell biological evidence that GRAF1
      interacted with a network of endocytic and adhesion proteins and was found
      enriched at podosome-like adhesions and src-induced podosomes. We further
      demonstrate that these sites comprise microdomains of highly ordered lipid
      enriched in GRAF1 endocytic cargo. GRAF1 activity was upregulated in spreading
      cells and uptake via CLICs was concentrated at the leading edge of migrating
      cells. Depletion of GRAF1, which inhibits CLIC generation, resulted in profound
      defects in cell spreading and migration. We propose that GRAF1 remodels membrane
      microdomains at adhesion sites into endocytic carriers, facilitating membrane
      turnover during cell morphological changes.

PMID- 21965291
TI  - Genome-wide analysis of yeast stress survival and tolerance acquisition to
      analyze the central trade-off between growth rate and cellular robustness.
AB  - All organisms have evolved to cope with changes in environmental conditions,
      ensuring the optimal combination of proliferation and survival. In yeast,
      exposure to a mild stress leads to an increased tolerance for other stresses.
      This suggests that yeast uses information from the environment to prepare for
      future threats. We used the yeast knockout collection to systematically
      investigate the genes and functions involved in severe stress survival and in the
      acquisition of stress (cross-) tolerance. Besides genes and functions relevant
      for survival of heat, acid, and oxidative stress, we found an inverse correlation
      between mutant growth rate and stress survival. Using chemostat cultures, we
      confirmed that growth rate governs stress tolerance, with higher growth
      efficiency at low growth rates liberating the energy for these investments.
      Cellular functions required for stress tolerance acquisition, independent of the
      reduction in growth rate, were involved in vesicular transport, the Rpd3 histone
      deacetylase complex, and the mitotic cell cycle. Stress resistance and acquired
      stress tolerance in Saccharomyces cerevisiae are governed by a combination of
      stress-specific and general processes. The reduction of growth rate, irrespective
      of the cause of this reduction, leads to redistribution of resources toward
      stress tolerance functions, thus preparing the cells for impending change.

PMID- 21965293
TI  - Cx50 requires an intact PDZ-binding motif and ZO-1 for the formation of
      functional intercellular channels.
AB  - The three connexins expressed in the ocular lens each contain PDZ domain-binding
      motifs directing a physical association with the scaffolding protein ZO-1, but
      the significance of the interaction is unknown. We found that Cx50 with PDZ
      binding motif mutations did not form gap junction plaques or induce cell-cell
      communication in HeLa cells, whereas the addition of a seven-amino acid PDZ
      binding motif restored normal function to Cx50 lacking its entire C-terminal
      cytoplasmic domain. C-Terminal deletion had a similar although weaker effect on
      Cx46 but little if any effect on targeting and function of Cx43. Furthermore,
      small interfering RNA knockdown of ZO-1 completely inhibited the formation of gap
      junctions by wild-type Cx50 in HeLa cells. Thus both a PDZ-binding motif and ZO-1
      are necessary for Cx50 intercellular channel formation in HeLa cells. Knock-in
      mice expressing Cx50 with a PDZ-binding motif mutation phenocopied Cx50
      knockouts. Furthermore, differentiating lens fibers in the knock-in displayed
      extensive intracellular Cx50, whereas plaques in mature fibers contained only
      Cx46. Thus normal Cx50 function in vivo also requires an intact PDZ domain
      binding motif. This is the first demonstration of a connexin-specific requirement
      for a connexin-interacting protein in gap junction assembly.

PMID- 21965294
TI  - Evolutionary development of redundant nuclear localization signals in the mRNA
      export factor NXF1.
AB  - In human cells, the mRNA export factor NXF1 resides in the nucleoplasm and at
      nuclear pore complexes. Karyopherin beta2 or transportin recognizes a proline
      tyrosine nuclear localization signal (PY-NLS) in the N-terminal tail of NXF1 and
      imports it into the nucleus. Here biochemical and cellular studies to understand
      the energetic organization of the NXF1 PY-NLS reveal unexpected redundancy in the
      nuclear import pathways used by NXF1. Human NXF1 can be imported via importin
      beta, karyopherin beta2, importin 4, importin 11, and importin alpha. Two NLS
      epitopes within the N-terminal tail, an N-terminal basic segment and a C-terminal
      R-X(2-5)-P-Y motif, provide the majority of binding energy for all five
      karyopherins. Mutation of both NLS epitopes abolishes binding to the
      karyopherins, mislocalized NXF1 to the cytoplasm, and significantly compromised
      its mRNA export function. The understanding of how different karyopherins
      recognize human NXF1, the examination of NXF1 sequences from divergent
      eukaryotes, and the interactions of NXF1 homologues with various karyopherins
      reveals the evolutionary development of redundant NLSs in NXF1 of higher
      eukaryotes. Redundancy of nuclear import pathways for NXF1 increases
      progressively from fungi to nematodes and insects to chordates, potentially
      paralleling the increasing complexity in mRNA export regulation and the evolution
      of new nuclear functions for NXF1.

PMID- 21965295
TI  - NOX4 mediates activation of FoxO3a and matrix metalloproteinase-2 expression by
      urotensin-II.
AB  - The vasoactive peptide urotensin-II (U-II) has been associated with vascular
      remodeling in different cardiovascular disorders. Although U-II can induce
      reactive oxygen species (ROS) by the NADPH oxidase NOX4 and stimulate smooth
      muscle cell (SMC) proliferation, the precise mechanisms linking U-II to vascular
      remodeling processes remain unclear. Forkhead Box O (FoxO) transcription factors
      have been associated with redox signaling and control of proliferation and
      apoptosis. We thus hypothesized that FoxOs are involved in the SMC response
      toward U-II and NOX4. We found that U-II and NOX4 stimulated FoxO activity and
      identified matrix metalloproteinase-2 (MMP2) as target gene of FoxO3a. FoxO3a
      activation by U-II was preceded by NOX4-dependent phosphorylation of c-Jun NH(2)
      terminal kinase and 14-3-3 and decreased interaction of FoxO3a with its inhibitor
      14-3-3, allowing MMP2 transcription. Functional studies in FoxO3a-depleted SMCs
      and in FoxO3a(-/-) mice showed that FoxO3a was important for basal and U-II
      stimulated proliferation and vascular outgrowth, whereas treatment with an MMP2
      inhibitor blocked these responses. Our study identified U-II and NOX4 as new
      activators of FoxO3a, and MMP2 as a novel target gene of FoxO3a, and showed that
      activation of FoxO3a by this pathway promotes vascular growth. FoxO3a may thus
      contribute to progression of cardiovascular diseases associated with vascular
      remodeling.

PMID- 21965296
TI  - Structural basis of the myosin X PH1(N)-PH2-PH1(C) tandem as a specific and acute
      cellular PI(3,4,5)P(3) sensor.
AB  - Myosin X (MyoX) is an unconventional myosin that is known to induce the formation
      and elongation of filopodia in many cell types. MyoX-induced filopodial induction
      requires the three PH domains in its tail region, although with unknown
      underlying molecular mechanisms. MyoX's first PH domain is split into halves by
      its second PH domain. We show here that the PH1(N)-PH2-PH1(C) tandem allows MyoX
      to bind to phosphatidylinositol (3,4,5)-triphosphate [PI(3,4,5)P(3)] with high
      specificity and cooperativity. We further show that PH2 is responsible for the
      specificity of the PI(3,4,5)P(3) interaction, whereas PH1 functions to enhance
      the lipid membrane-binding avidity of the tandem. The structure of the MyoX
      PH1(N)-PH2-PH1(C) tandem reveals that the split PH1, PH2, and the highly
      conserved interdomain linker sequences together form a rigid supramodule with two
      lipid-binding pockets positioned side by side for binding to phosphoinositide
      membrane bilayers with cooperativity. Finally, we demonstrate that disruption of
      PH2-mediated binding to PI(3,4,5)P(3) abolishes MyoX's function in inducing
      filopodial formation and elongation.

PMID- 21965297
TI  - The microtubule lattice and plus-end association of Drosophila Mini spindles is
      spatially regulated to fine-tune microtubule dynamics.
AB  - Individual microtubules (MTs) exhibit dynamic instability, a behavior in which
      they cycle between phases of growth and shrinkage while the total amount of MT
      polymer remains constant. Dynamic instability is promoted by the conserved
      XMAP215/Dis1 family of microtubule-associated proteins (MAPs). In this study, we
      conducted an in vivo structure-function analysis of the Drosophila homologue Mini
      spindles (Msps). Msps exhibits EB1-dependent and spatially regulated MT
      localization, targeting to microtubule plus ends in the cell interior and
      decorating the lattice of growing and shrinking microtubules in the cell
      periphery. RNA interference rescue experiments revealed that the NH(2)-terminal
      four TOG domains of Msps function as paired units and were sufficient to promote
      microtubule dynamics and EB1 comet formation. We also identified TOG5 and novel
      inter-TOG linker motifs that are required for targeting Msps to the microtubule
      lattice. These novel microtubule contact sites are necessary for the interplay
      between the conserved TOG domains and inter-TOG MT binding that underlies the
      ability of Msps to promote MT dynamic instability.

PMID- 21965298
TI  - Arginine methylation by PRMT1 regulates nuclear-cytoplasmic localization and
      toxicity of FUS/TLS harbouring ALS-linked mutations.
AB  - Mutations in FUS/TLS (fused in sarcoma/translated in liposarcoma) cause an
      inheritable form of amyotrophic lateral sclerosis (ALS6). In contrast to FUS(WT),
      which is concentrated in the nucleus, these mutants are abnormally distributed in
      the cytoplasm where they form inclusions and associate with stress granules. The
      data reported herein demonstrate the importance of protein arginine methylation
      in nuclear-cytoplasmic shuttling of FUS and abnormalities of ALS-causing mutants.
      Depletion of protein arginine methyltransferase 1 (PRMT1; the enzyme that
      methylates FUS) in mouse embryonic fibroblasts by gene knockout, or in human
      HEK293 cells by siRNA knockdown, diminished the ability of ALS-linked FUS mutants
      to localize to the cytoplasm and form inclusions. To examine properties of FUS
      mutants in the context of neurons vulnerable to the disease, FUS(WT) and ALS
      linked FUS mutants were expressed in motor neurons of dissociated murine spinal
      cord cultures. In motor neurons, shRNA-mediated PRMT1 knockdown concomitant with
      the expression of FUS actually accentuated the shift in distribution of ALS
      linked FUS mutants from the nucleus to the cytoplasm. However, when PRMT1 was
      inhibited prior to expression of ALS-linked FUS mutants, by pretreatment with a
      global methyltransferase inhibitor, ALS-linked FUS mutants were sequestered in
      the nucleus and cytoplasmic inclusions were reduced, as in the cell lines.
      Mitochondria were significantly shorter in neurons with cytoplasmic ALS-linked
      FUS mutants, a factor that could contribute to toxicity. We propose that arginine
      methylation by PRMT1 participates in the nuclear-cytoplasmic shuttling of FUS,
      particularly of ALS6-associated mutants, and thus contributes to the toxic gain
      of function conferred by these disease-causing mutations.

PMID- 21965299
TI  - Mitochondrial complex III stabilizes complex I in the absence of NDUFS4 to
      provide partial activity.
AB  - Mitochondrial complex I (CI) is a multi-subunit enzyme that forms the major entry
      point of nicotinamide adenine dinucleotide (NADH) electrons into the respiratory
      chain. Mutations in the NDUFS4 gene, encoding an accessory subunit of this
      complex, cause a Leigh-like phenotype in humans. To study the nature and
      penetrance of the CI defect in different tissues, we investigated the role of
      NDUFS4 in mice with fatal mitochondrial encephalomyopathy, caused by a systemic
      inactivation of the Ndufs4 gene. We report that the absence of NDUFS4 in
      different mouse tissues results in decreased activity and stability of CI. This
      CI instability leads to an increased disconnection of electron influx of the NADH
      dehydrogenase module from the holo-complex. However, the formation of respiratory
      supercomplexes still allows formation of active CI in these Ndufs4 knock-out
      mice. These results reveal the importance of these supramolecular interactions
      not only for stabilization but also for the assembly of CI, which becomes
      especially relevant in pathological conditions.

PMID- 21965300
TI  - Charcot-Marie-Tooth disease CMT4A: GDAP1 increases cellular glutathione and the
      mitochondrial membrane potential.
AB  - Mutations in GDAP1 lead to recessively or dominantly inherited peripheral
      neuropathies (Charcot-Marie-Tooth disease, CMT), indicating that GDAP1 is
      essential for the viability of cells in the peripheral nervous system. GDAP1
      contains domains characteristic of glutathione-S-transferases (GSTs), is located
      in the outer mitochondrial membrane and induces fragmentation of mitochondria. We
      found GDAP1 upregulated in neuronal HT22 cells selected for resistance against
      oxidative stress. GDAP1 over-expression protected against oxidative stress caused
      by depletion of the intracellular antioxidant glutathione (GHS) and against
      effectors of GHS depletion that affect the mitochondrial membrane integrity like
      truncated BH3-interacting domain death agonist and 12/15-lipoxygenase. Gdap1
      knockdown, in contrast, increased the susceptibility of motor neuron-like NSC34
      cells against GHS depletion. Over-expression of wild-type GDAP1, but not of GDAP1
      with recessively inherited mutations that cause disease and reduce fission
      activity, increased the total cellular GHS content and the mitochondrial membrane
      potential up to a level where it apparently limits mitochondrial respiration,
      leading to reduced mitochondrial Ca(2+) uptake and superoxide production.
      Fibroblasts from autosomal-recessive CMT4A patients had reduced GDAP1 levels,
      reduced GHS concentration and a reduced mitochondrial membrane potential. Thus,
      our results suggest that the potential GST GDAP1 is implicated in the control of
      the cellular GHS content and mitochondrial activity, suggesting an involvement of
      oxidative stress in the pathogenesis of CMT4A.

PMID- 21965301
TI  - Dysfunctions in endosomal-lysosomal and autophagy pathways underlie
      neuropathology in a mouse model for Lafora disease.
AB  - Lafora progressive myoclonus epilepsy (also known as Lafora disease, LD) is an
      inherited and fatal form of a neurodegenerative disorder characterized by the
      presence of carbohydrate-rich inclusions called Lafora bodies. LD can be caused
      by defects in the laforin phosphatase or the malin ubiquitin ligase and the
      clinical symptoms resulting from these two defects are almost similar. In order
      to understand the molecular basis of LD pathogenesis and the role of Lafora
      bodies in neuropathology, we have studied the laforin-deficient mice as a model
      and show here that Lafora bodies recruit proteasomal subunit, endoplasmic
      reticulum chaperone GRP78/Bip, autophagic protein p62 and endosomal regulators
      Rab5 and Rab7. The laforin-deficient brain also reveals the proliferation of
      enlarged lysosomes, lipofuscin granules, amyloid-beta peptides and increased
      levels of insoluble form of ubiquitinated protein, indicating a significant
      impairment in the cellular degradative pathway. Further, abnormal dendrites and
      increased gliosis, especially at the vicinity of Lafora bodies, were noted in the
      LD brain. Taken together, our study suggests that the neuropathology in LD is not
      limited to Lafora bodies, that some of the neuropathological changes in LD are
      likely to be secondary effects caused by Lafora bodies, and that impairment in
      the autophagy-endosomal-lysosomal pathways might underlie some of the symptoms in
      LD.

PMID- 21965303
TI  - Survival of pancreatic beta cells is partly controlled by a TCF7L2-p53-p53INP1
      dependent pathway.
AB  - The transcription factor T-cell factor 7-like 2 (TCF7L2) confers type 2 diabetes
      risk mainly through impaired insulin secretion, perturbed incretin effect and
      reduced beta-cell survival. The aim of this study was to identify the molecular
      mechanism through which TCF7L2 influences beta-cell survival. TCF7L2 target genes
      in INS-1 cells were identified using Chromatin Immunoprecipitation. Validation of
      targets was obtained by: siRNA silencing, real-time quantitative polymerase chain
      reaction, electrophoretic mobility shift assay, luciferase reporter assays and
      western blot. Apoptosis rate was measured by DNA degradation and caspase-3
      content. Islet viability was estimated by measuring metabolic rate. TCF7L2 binds
      to 3646 gene promoters in INS-1 cells in high or low glucose, including Tp53,
      Pten, Uggt1, Adamts9 and Fto. SiRNA-mediated reduction in TCF7L2 activity
      resulted in increased apoptosis and increased expression of Tp53, which resulted
      in elevated p53 protein activity and an increased expression of the p53 target
      gene Tp53inp1 (encoding p53-induced-nuclear-protein 1). Reversing the increase in
      p53INP1 protein expression, seen after Tcf7l2 silencing, protected INS-1 cells
      from Tcf7l2 depletion-induced apoptosis. This result was replicated in primary
      rat islets. The risk T-allele of rs7903146 is associated with increased TCF7L2
      mRNA expression and transcriptional activity. On the other hand, in vitro
      silencing of TCF7L2 lead to increased apoptosis. One possibility is that the risk
      T-allele increases expression of an inhibitory TCF7L2 isoform with lower
      transcriptional activity. These results identify the p53-p53INP1 pathway as a
      molecular mechanism through which TCF7L2 may affect beta-cell survival and
      established a molecular link between Tcf7l2 and two type 2 diabetes-associated
      genes, Tp53inp1 and Adamts9.

PMID- 21965302
TI  - NMNAT suppresses tau-induced neurodegeneration by promoting clearance of
      hyperphosphorylated tau oligomers in a Drosophila model of tauopathy.
AB  - Tauopathies, including Alzheimer's disease, are a group of neurodegenerative
      diseases characterized by abnormal tau hyperphosphorylation that leads to
      formation of neurofibrillary tangles. Drosophila models of tauopathy display
      prominent features of the human disease including compromised lifespan,
      impairments of learning, memory and locomotor functions and age-dependent
      neurodegeneration visible as vacuolization. Here, we use a Drosophila model of
      frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), in
      order to study the neuroprotective capacity of a recently identified neuronal
      maintenance factor, nicotinamide mononucleotide (NAD) adenylyl transferase
      (NMNAT), a protein that has both NAD synthase and chaperone function. NMNAT is
      essential for maintaining neuronal integrity under normal conditions and has been
      shown to protect against several neurodegenerative conditions. However, its
      protective role in tauopathy has not been examined. Here, we show that
      overexpression of NMNAT significantly suppresses both behavioral and
      morphological deficits associated with tauopathy by means of reducing the levels
      of hyperphosphorylated tau oligomers. Importantly, the protective activity of
      NMNAT protein is independent of its NAD synthesis activity, indicating a role for
      direct protein-protein interaction. Next, we show that NMNAT interacts with
      phosphorylated tau in vivo and promotes the ubiquitination and clearance of toxic
      tau species. Consequently, apoptosis activation was significantly reduced in
      brains overexpressing NMNAT, and neurodegeneration was suppressed. Our report on
      the molecular basis of NMNAT-mediated neuroprotection in tauopathies opens future
      investigation of this factor in other protein foldopathies.

PMID- 21965304
TI  - Small bowel obstruction as the primary presentation of undiagnosed metastatic
      lobular breast carcinoma.
AB  - Breast carcinoma continues to be the most common neoplasm in women, with a
      lifetime risk affecting approximately 1 in 8. Factors affecting prognosis include
      the size and grade of the primary lesion, regional axillary lymphadenopathy, the
      presence of hormonal receptors, and distant metastatic disease. Although
      metastatic breast disease usually affects the lungs, bones, and brain, abdominal
      association is not as common. Interestingly, lobular carcinoma, a subtype that
      only accounts for a minor portion of breast cancers, usually has luminal gastro
      intestinal involvement. We describe a 57-year old Caucasian female with recurrent
      episodes of abdominal pain and concurrent intermittent obstructive symptomatology
      with overflow diarrhea over a one-year period. Conventional endoscopic and
      imaging workup was unrevealing. Capsule endoscopy was used, but this caused a
      complete bowel obstruction necessitating surgery, and subsequent resection of a
      strictured segment. Pathological examination yielded metastatic adenocarcinoma,
      consistent with origin in breast, lobular type. Immunohistochemistry confirmed
      the origin. Luminal gastro-intestinal involvement is a rare, yet recognized, site
      of breast adenocarcinoma metastasis; it is even more uncommon with an undiagnosed
      primary. It may mimic other gastro-intestinal disease, and as such, it would be
      prudent to maintain a modest index of suspicion given the high prevalence of
      breast neoplasia.

PMID- 21965305
TI  - Surgically placed wound catheters (SPWC) and local anaesthetic infusion in breast
      surgery: efficacy and safety analysis.
AB  - BACKGROUND: The effectiveness of surgically placed wound catheters (SPWC) and
      local anaesthetic infusion in the management of post-operative pain following
      breast surgery is controversial. This meta-analysis was performed to assess
      efficacy SPWC compared to other techniques of pain management. MATERIAL AND
      METHODS: The meta-analysis included randomised control trials that compared SPWC
      with other forms of pain control. Post-operative opioid requirements and pain
      measured in visual analogue scale (VAS) were analysed using Comprehensive Meta
      analysis Software version 2. Literature was reviewed for the safety of the SPWC
      and local anaesthetic infusion. RESULTS: Four randomised controlled trials
      evaluating 147 women were included in the final analysis. The overall standard
      difference in means was 0.094 and 0.033 for post-operative opioid requirement and
      pain respectively favouring the SPWC and local anaesthetic infusion group. It is
      a safe technique with no major adverse events as a result. CONCLUSION: Surgically
      placed wound catheters and local anaesthetic infusion is clinically safe in a
      wide range of surgical procedures on the breast and there appears to be a trend
      towards improved post operative pain relief. The studies analyzed in this review
      have several important drawbacks such as inadequate power to detect significant
      differences (none of them included more than 50 patients). A well designed RCT of
      patients undergoing breast surgery with an adequate number is of patients
      required to emphatically demonstrate if the operative site infusion with local
      anaesthetic solution postoperatively is safe and efficacious compared to opioid
      based regimens alone for post operative pain relief.

PMID- 21965306
TI  - Breast cancer predisposition and brain hemispheric laterality specification
      likely share a common genetic cause.
AB  - The majority of breast cancer cases seen in women remain unexplained by simple
      Mendelian genetics. It is generally hypothesized that such non-familial, so
      called sporadic cases, result from exposure of the affected individuals to a
      cancer-causing environment and/or from stochastic cell biological errors.
      Clearly, adverse environment exposure can cause disease, but is that necessarily
      the cause of most sporadic cases? Curiously, female breast cancer patients who
      were selected to prefer right-hand-use reportedly exhibited a higher incidence of
      reversed-brain hemispheric laterality when compared to that of the public at
      large. Notably, such a higher level of hemispheric reversal is also found in
      healthy, left-handed or ambidextrous persons. Based on the association between
      these disparate traits, a new hypothesis for the etiology of sporadic breast
      cancer cases is advanced here; breast cancer predisposition and brain laterality
      development likely share a common genetic cause.

PMID- 21965307
TI  - Fibroadenoma in male breast: case report and literature review.
AB  - We report a rare case of mammary fibroadenoma in a 75 year old male patient with
      emphasis on imaging findings and review of the previously reported cases.

PMID- 21965308
TI  - Mouse models of triple negative [basal-like/claudin low] breast cancer.
AB  - Triple negative breast cancer encompasses the molecular subtypes of basal-like
      and the more recently defined claudin-low group. In this review, we discuss the
      identification and characterization of mouse models that mimic these human
      subtypes. These mouse models serve as useful tools for the study of disease
      biology and represent a valuable resource for the evaluation of experimental
      therapeutics.

PMID- 21965310
TI  - Editorial: granulopoiesis versus monopoiesis: a consequence of transcription
      factors dancing with the right partners.

PMID- 21965309
TI  - Epidemiology of triple negative breast cancers.
AB  - Triple negative (TN) breast cancers fail to express the three most common breast
      cancer receptors; i.e., estrogen receptor (ER), progesterone receptor (PR), and
      human epidermal growth factor receptor-2 (HER2). Accumulating data demonstrate
      that epidemiological risk factor profiles also vary between TN (ER-PR-HER2-) and
      other breast cancers, especially the so-called Luminal A breast cancers (ER+PR +/
      HER2-) [1]. A more comprehensive understanding of the epidemiology of TN breast
      cancers has important public health implications for risk assessment [2],
      prevention and treatment. The epidemiology of TN breast cancers can be first
      understood in the age-related reproductive risk factor patterns for ER, PR, and
      HER2. For example, there is a clear and strong association between older age at
      diagnosis (and therefore postmenopausal status) and the development of ER
      positive, PR positive, and HER2 negative breast cancers. On the other hand,
      younger age at diagnosis (and premenopausal status) is related to the development
      of ER negative, PR negative, and HER2 positive breast cancers. This gives rise to
      the somewhat counterintuitive suggestion that menopause has a greater relative
      impact upon hormone receptor negative than positive breast cancers [3,4].
      Throughout this review, we will primarily contrast ER-PR-HER2- (TN) with ER+PR +/
      HER2- (Luminal A) breast cancers. We will first summarize the population-based
      age-specific incidence rate patterns and clinical outcomes, and then will review
      the available analytical studies. Information sources for this review included
      the National Cancer Institute's Surveillance, Epidemiology, and End Results 13
      Registries Public-Use Database [5], CANCERLIT, Index Medicus, and PubMed.

PMID- 21965311
TI  - Editorial: developmental regulation of P-glycoprotein and HIV therapy: spare the
      thymus but spoil the child?

PMID- 21965312
TI  - 37 years of body mass index and dementia: observations from the prospective
      population study of women in Gothenburg, Sweden.
AB  - Level of adiposity is linked to dementia in epidemiological studies. Overweight
      and obesity in mid- and late-life may increase risk for dementia, whereas decline
      in body weight or body mass index (BMI) and underweight in years preceding and at
      the time of a dementia diagnosis may also relate to dementia. Longitudinal
      studies with sufficient follow-up are necessary to estimate trajectories that
      allow better understanding of the relationship between adiposity indices and
      dementia over the life course. We evaluated the natural history of BMI in
      relationship to clinical dementia over 37 years in the Prospective Population
      Study of Women (PPSW) in Sweden. PPSW is a systematic sample of 1462 women born
      1908, 1914, 1918, 1922, and 1930 and aged 38-60 years at baseline. Examinations
      occurred in 1968, 1974, 1980, 1992, 2000, and 2005. Statistical analyses were
      conducted using mixed effects regression models. Trajectories of BMI over 37
      years as a function of age differed between women who did versus did not develop
      dementia. Women developing dementia evidenced a lesser increase in BMI from age
      38 to 70 years. After age 70, the BMI slope decreased similarly (no "accelerated
      decline") irrespective of dementia status. A lower BMI before and during dementia
      onset was observed. Women with similar BMI at mid-life exhibited a different
      pattern of BMI change as they approached late-life that was related to dementia
      onset. BMI may be a potential marker of dementia-related neuropathologies in the
      brain. Dementia is related to a common risk factor, BMI, from mid-to late-life.

PMID- 21965314
TI  - ESHRE special interest group for andrology basic semen analysis course: a
      continued focus on accuracy, quality, efficiency and clinical relevance.
AB  - ESHRE has been running courses for basic semen analysis since 1994 and course
      material has been updated regularly in response to new findings and publications.
      Following publication of the 5th edition of the WHO laboratory manual, entitled
      WHO Laboratory Manual for the Examination and Processing of Human Semen (WHO5),
      the Subcommittee for training of the ESHRE Special Interest Group for Andrology
      evaluated potential amendments to its course. In respect of the updated ESHRE
      course, there are eight particular areas of discourse that are reviewed (i)
      maintaining the four-class differential motility count allowing distinction
      between rapid and slow progressive sperm for assisted reproduction technology.
      (ii) Maintaining the four-category assessment for sperm morphology with
      calculation of the teratozoospermic index. (iii) Continuing to advocate the use
      of three categories of results: 'normal', 'borderline' and 'abnormal' with
      respect to the clinical interpretation of the data. (iv) Presenting clear and
      unequivocal methods for performing assessments e.g. morphology. (v) Correcting
      the inconsistencies in WHO5, some of which are actually erroneous. (vi) Reducing
      the requirements for substantial extra work for what are unestablished
      improvements in accuracy and/or precision in the final results. (vii)
      Presentation of logical methods of sperm preparation. (viii) Discussion of the
      suddenly changed limits between fertile and subfertile men.

PMID- 21965313
TI  - Dyslipidemia and dementia: current epidemiology, genetic evidence, and mechanisms
      behind the associations.
AB  - The role of cholesterol in the etiology of Alzheimer's disease (AD) is still
      controversial. Some studies exploring the association between lipids and/or lipid
      lowering treatment and AD indicate a harmful effect of dyslipidemia and a
      beneficial effect of statin therapy on AD risk. The findings are supported by
      genetic linkage and association studies that have clearly identified several
      genes involved in cholesterol metabolism or transport as AD susceptibility genes,
      including apolipoprotein E, apolipoprotein J, and the sortilin-related receptor.
      Functional cell biology studies support a critical involvement of lipid raft
      cholesterol in the modulation of amyloid-beta protein precursor (AbetaPP)
      processing by beta- and gamma-secretase resulting in altered amyloid-beta
      production. Contradictory evidence comes from epidemiological studies showing no
      or controversial association between dyslipidemia and AD risk. Additionally, cell
      biology studies suggest that there is little exchange between circulating and
      brain cholesterol, that increased membrane cholesterol is protective by
      inhibiting loss of membrane integrity through amyloid cytotoxicity, and that
      cellular cholesterol inhibits co-localization of BACE1 and AbetaPP in non-raft
      membrane domains, thereby increasing generation of plasmin, an amyloid-beta
      degrading enzyme. The aim of this review is to summarize the findings of
      epidemiological and cell biological studies to elucidate the role of cholesterol
      in AD etiology.

PMID- 21965316
TI  - Some thoughts on appointment intervals.

PMID- 21965315
TI  - Arylsulfatase A deficiency causes seminolipid accumulation and a lysosomal
      storage disorder in Sertoli cells.
AB  - Sulfogalactosylglycerolipid (SGG) is the major sulfoglycolipid of male germ
      cells. During spermatogenesis, apoptosis occurs in >50% of total germ cells.
      Sertoli cells phagocytose these apoptotic germ cells and degrade their components
      using lysosomal enzymes. Here we demonstrated that SGG was a physiological
      substrate of Sertoli lysosomal arylsulfatase A (ARSA). SGG accumulated in Sertoli
      cells of Arsa(-/-) mice, and at 8 months of age, this buildup led to lysosomal
      swelling and other cellular abnormalities typical of a lysosomal storage
      disorder. This disorder likely compromised Sertoli cell functions, manifesting as
      impaired spermatogenesis and production of sperm with near-zero fertilizing
      ability in vitro. Fecundity of Arsa(-/-) males was thus reduced when they were
      older than 5 months. Sperm SGG is known for its roles in fertilization.
      Therefore, the minimal sperm fertilizing ability of 8-month-old Arsa(-/-) males
      may be explained by the 50% reduction of their sperm SGG levels, a result that
      was also observed in testicular germ cells. These unexpected decreases in SGG
      levels might be partly due to depletion of the backbone lipid
      palmitylpalmitoylglycerol that is generated from the SGG degradation pathway in
      Sertoli cells and normally recycled to new generations of primary spermatocytes
      for SGG synthesis.

PMID- 21965317
TI  - Molar distalization with a miniscrew-anchored sliding jig.

PMID- 21965318
TI  - Evidence-based considerations for determining appointment intervals.

PMID- 21965319
TI  - Securing pontics in an Essix retainer.

PMID- 21965320
TI  - In-office digital study models.

PMID- 21965321
TI  - The readers' corner.

PMID- 21965322
TI  - Autotransplantation of premolars in a patient with multiple congenitally missing
      teeth.

PMID- 21965323
TI  - Investigations of a compartmental model for leucine kinetics using non-linear
      mixed effects models with ordinary and stochastic differential equations.
AB  - Non-linear mixed effects (NLME) models represent a powerful tool to
      simultaneously analyse data from several individuals. In this study, a
      compartmental model of leucine kinetics is examined and extended with a
      stochastic differential equation to model non-steady-state concentrations of free
      leucine in the plasma. Data obtained from tracer/tracee experiments for a group
      of healthy control individuals and a group of individuals suffering from diabetes
      mellitus type 2 are analysed. We find that the interindividual variation of the
      model parameters is much smaller for the NLME models, compared to traditional
      estimates obtained from each individual separately. Using the mixed effects
      approach, the population parameters are estimated well also when only half of the
      data are used for each individual. For a typical individual, the amount of free
      leucine is predicted to vary with a standard deviation of 8.9% around a mean
      value during the experiment. Moreover, leucine degradation and protein uptake of
      leucine is smaller, proteolysis larger and the amount of free leucine in the body
      is much larger for the diabetic individuals than the control individuals. In
      conclusion, NLME models offers improved estimates for model parameters in complex
      models based on tracer/tracee data and may be a suitable tool to reduce data
      sampling in clinical studies.

PMID- 21965324
TI  - A (heat) shock to the system promotes peripheral nerve regeneration.
AB  - Peripheral nerves are easily damaged, resulting in loss of motor and sensory
      function. Recovery of motor and sensory function after peripheral nerve injury is
      suboptimal, even after appropriate surgical repair. This is due to the slow rate
      of axonal elongation during regeneration and atrophic changes that occur in
      denervated Schwann cells and target muscle with proximal lesions. One way to
      solve this problem is to accelerate the rate at which the axons regenerate. In
      this issue of the JCI, Ma and colleagues show that this can be achieved in mice
      by overexpression of heat shock protein 27, providing hope for enhanced
      functional recovery in patients after peripheral nerve damage.

PMID- 21965325
TI  - MLK3 regulates bone development downstream of the faciogenital dysplasia protein
      FGD1 in mice.
AB  - Mutations in human FYVE, RhoGEF, and PH domain-containing 1 (FGD1) cause
      faciogenital dysplasia (FGDY; also known as Aarskog syndrome), an X-linked
      disorder that affects multiple skeletal structures. FGD1 encodes a guanine
      nucleotide exchange factor (GEF) that specifically activates the Rho GTPase
      CDC42. However, the mechanisms by which mutations in FGD1 affect skeletal
      development are unknown. Here, we describe what we believe to be a novel
      signaling pathway in osteoblasts initiated by FGD1 that involves the MAP3K mixed
      lineage kinase 3 (MLK3). We observed that MLK3 functions downstream of FGD1 to
      regulate ERK and p38 MAPK, which in turn phosphorylate and activate the master
      regulator of osteoblast differentiation, Runx2. Mutations in FGD1 found in
      individuals with FGDY ablated its ability to activate MLK3. Consistent with our
      description of this pathway and the phenotype of patients with FGD1 mutations,
      mice with a targeted deletion of Mlk3 displayed multiple skeletal defects,
      including dental abnormalities, deficient calvarial mineralization, and reduced
      bone mass. Furthermore, mice with knockin of a mutant Mlk3 allele that is
      resistant to activation by FGD1/CDC42 displayed similar skeletal defects,
      demonstrating that activation of MLK3 specifically by FGD1/CDC42 is important for
      skeletal mineralization. Thus, our results provide a putative biochemical
      mechanism for the skeletal defects in human FGDY and suggest that modulating MAPK
      signaling may benefit these patients.

PMID- 21965326
TI  - Signaling via the prostaglandin E2 receptor EP4 exerts neuronal and vascular
      protection in a mouse model of cerebral ischemia.
AB  - Stroke is the third leading cause of death in the United States. Fewer than 5% of
      patients benefit from the only intervention approved to treat stroke. Thus, there
      is an enormous need to identify new therapeutic targets. The role of inducible
      cyclooxygenase (COX-2) activity in stroke and other neurologic diseases is
      complex, as both activation and sustained inhibition can engender cerebral
      injury. Whether COX-2 induces cerebroprotective or injurious effects is probably
      dependent on which downstream prostaglandin receptors are activated. Here, we
      investigated the function of the PGE2 receptor EP4 in a mouse model of cerebral
      ischemia. Systemic administration of a selective EP4 agonist after ischemia
      reduced infarct volume and ameliorated long-term behavioral deficits. Expression
      of EP4 was robust in neurons and markedly induced in endothelial cells after
      ischemia-reperfusion, suggesting that neuronal and/or endothelial EP4 signaling
      imparts cerebroprotection. Conditional genetic inactivation of neuronal EP4
      worsened stroke outcome, consistent with an endogenous protective role of
      neuronal EP4 signaling in vivo. However, endothelial deletion of EP4 also
      worsened stroke injury and decreased cerebral reperfusion. Systemic
      administration of an EP4 agonist increased levels of activated eNOS in cerebral
      microvessels, an effect that was abolished with conditional deletion of
      endothelial EP4. Thus, our data support the concept of targeting protective
      prostaglandin receptors therapeutically after stroke.

PMID- 21965327
TI  - Gadd45beta is an inducible coactivator of transcription that facilitates rapid
      liver growth in mice.
AB  - The growth arrest and DNA damage-inducible 45 (Gadd45) proteins act in many
      cellular processes. In the liver, Gadd45b (encoding Gadd45beta) is the gene most
      strongly induced early during both compensatory regeneration and drug-induced
      hyperplasia. The latter response is associated with the dramatic and rapid
      hepatocyte growth that follows administration of the xenobiotic TCPOBOP (1,4
      bis[2-(3,5)-dichoropyridyloxy] benzene), a ligand of the nuclear receptor
      constitutive androstane receptor (CAR). Here, we have shown that Gadd45b-/- mice
      have intact proliferative responses following administration of a single dose of
      TCPOBOP, but marked growth delays. Moreover, early transcriptional stimulation of
      CAR target genes was weaker in Gadd45b-/- mice than in wild-type animals, and
      more genes were downregulated. Gadd45beta was then found to have a direct role in
      transcription by physically binding to CAR, and TCPOBOP treatment caused both
      proteins to localize to a regulatory element for the CAR target gene cytochrome
      P450 2b10 (Cyp2b10). Further analysis defined separate Gadd45beta domains that
      mediated binding to CAR and transcriptional activation. Although baseline hepatic
      expression of Gadd45b was broadly comparable to that of other coactivators, its
      140-fold stimulation by TCPOBOP was striking and unique. The induction of
      Gadd45beta is therefore a response that facilitates increased transcription,
      allowing rapid expansion of liver mass for protection against xenobiotic insults.

PMID- 21965328
TI  - Mouse model of enlarged vestibular aqueducts defines temporal requirement of
      Slc26a4 expression for hearing acquisition.
AB  - Mutations in human SLC26A4 are a common cause of hearing loss associated with
      enlarged vestibular aqueducts (EVA). SLC26A4 encodes pendrin, an anion-base
      exchanger expressed in inner ear epithelial cells that secretes HCO3- into
      endolymph. Studies of Slc26a4-null mice indicate that pendrin is essential for
      inner ear development, but have not revealed whether pendrin is specifically
      necessary for homeostasis. Slc26a4-null mice are profoundly deaf, with severe
      inner ear malformations and degenerative changes that do not model the less
      severe human phenotype. Here, we describe studies in which we generated a binary
      transgenic mouse line in which Slc26a4 expression could be induced with
      doxycycline. The transgenes were crossed onto the Slc26a4-null background so that
      all functional pendrin was derived from the transgenes. Varying the temporal
      expression of Slc26a4 revealed that E16.5 to P2 was the critical interval in
      which pendrin was required for acquisition of normal hearing. Lack of pendrin
      during this period led to endolymphatic acidification, loss of the endocochlear
      potential, and failure to acquire normal hearing. Doxycycline initiation at E18.5
      or discontinuation at E17.5 resulted in partial hearing loss approximating the
      human EVA auditory phenotype. These data collectively provide mechanistic insight
      into hearing loss caused by SLC26A4 mutations and establish a model for further
      studies of EVA-associated hearing loss.

PMID- 21965329
TI  - SCRIB expression is deregulated in human prostate cancer, and its deficiency in
      mice promotes prostate neoplasia.
AB  - Loss of cellular polarity is a hallmark of epithelial cancers, raising the
      possibility that regulators of polarity have a role in suppressing tumorigenesis.
      The Scribble complex is one of at least three interacting protein complexes that
      have a critical role in establishing and maintaining epithelial polarity. In
      human colorectal, breast, and endometrial cancers, expression of the Scribble
      complex member SCRIB is often mislocalized and deregulated. Here, we report that
      Scrib is indispensable for prostate homeostasis in mice. Scrib heterozygosity
      initiated prostate hyperplasia, while targeted biallelic Scrib loss predisposed
      mice to prostate intraepithelial neoplasia. Mechanistically, Scrib was shown to
      negatively regulate the MAPK cascade to suppress tumorigenesis. Further analysis
      revealed that prostate-specific loss of Scrib in mice combined with expression of
      an oncogenic Kras mutation promoted the progression of prostate cancer that
      recapitulated the human disease. The clinical significance of the work in mice
      was highlighted by our observation that SCRIB deregulation strongly correlated
      with poor survival in human prostate cancer. These data suggest that the polarity
      network could provide a new avenue for therapeutic intervention.

PMID- 21965330
TI  - Hepatic Sirt1 deficiency in mice impairs mTorc2/Akt signaling and results in
      hyperglycemia, oxidative damage, and insulin resistance.
AB  - Insulin resistance is a major risk factor for type 2 diabetes mellitus. The
      protein encoded by the sirtuin 1 (Sirt1) gene, which is a mouse homolog of yeast
      Sir2, is implicated in the regulation of glucose metabolism and insulin
      sensitivity; however, the underlying mechanism remains elusive. Here, using mice
      with a liver-specific null mutation of Sirt1, we have identified a signaling
      pathway involving Sirt1, Rictor (a component of mTOR complex 2 [mTorc2]), Akt,
      and Foxo1 that regulates gluconeogenesis. We found that Sirt1 positively
      regulates transcription of the gene encoding Rictor, triggering a cascade of
      phosphorylation of Akt at S473 and Foxo1 at S253 and resulting in decreased
      transcription of the gluconeogenic genes glucose-6-phosphatase (G6pase) and
      phosphoenolpyruvate carboxykinase (Pepck). Liver-specific Sirt1 deficiency caused
      hepatic glucose overproduction, chronic hyperglycemia, and increased ROS
      production. This oxidative stress disrupted mTorc2 and impaired mTorc2/Akt
      signaling in other insulin-sensitive organs, leading to insulin resistance that
      could be largely reversed with antioxidant treatment. These data delineate a
      pathway through which Sirt1 maintains insulin sensitivity and suggest that
      treatment with antioxidants might provide protection against progressive insulin
      resistance in older human populations.

PMID- 21965331
TI  - GATA3 controls Foxp3+ regulatory T cell fate during inflammation in mice.
AB  - Tregs not only keep immune responses to autoantigens in check, but also restrain
      those directed toward pathogens and the commensal microbiota. Control of
      peripheral immune homeostasis by Tregs relies on their capacity to accumulate at
      inflamed sites and appropriately adapt to their local environment. To date, the
      factors involved in the control of these aspects of Treg physiology remain poorly
      understood. Here, we show that the canonical Th2 transcription factor GATA3 is
      selectively expressed in Tregs residing in barrier sites including the
      gastrointestinal tract and the skin. GATA3 expression in both murine and human
      Tregs was induced upon TCR and IL-2 stimulation. Although GATA3 was not required
      to sustain Treg homeostasis and function at steady state, GATA3 played a cardinal
      role in Treg physiology during inflammation. Indeed, the intrinsic expression of
      GATA3 by Tregs was required for their ability to accumulate at inflamed sites and
      to maintain high levels of Foxp3 expression in various polarized or inflammatory
      settings. Furthermore, our data indicate that GATA3 limits Treg polarization
      toward an effector T cell phenotype and acquisition of effector cytokines in
      inflamed tissues. Overall, our work reveals what we believe to be a new facet in
      the complex role of GATA3 in T cells and highlights what may be a fundamental
      role in controlling Treg physiology during inflammation.

PMID- 21965332
TI  - A high-throughput single-cell analysis of human CD8+ T cell functions reveals
      discordance for cytokine secretion and cytolysis.
AB  - CD8+ T cells are a key component of the adaptive immune response to viral
      infection. An inadequate CD8+ T cell response is thought to be partly responsible
      for the persistent chronic infection that arises following infection with HIV. It
      is therefore critical to identify ways to define what constitutes an adequate or
      inadequate response. IFN-gamma production has been used as a measure of T cell
      function, but the relationship between cytokine production and the ability of a
      cell to lyse virus-infected cells is not clear. Moreover, the ability to assess
      multiple CD8+ T cell functions with single-cell resolution using freshly isolated
      blood samples, and subsequently to recover these cells for further functional
      analyses, has not been achieved. As described here, to address this need, we have
      developed a high-throughput, automated assay in 125-pl microwells to
      simultaneously evaluate the ability of thousands of individual CD8+ T cells from
      HIV-infected patients to mediate lysis and to produce cytokines. This concurrent,
      direct analysis enabled us to investigate the correlation between immediate
      cytotoxic activity and short-term cytokine secretion. The majority of in vivo
      primed, circulating HIV-specific CD8+ T cells were discordant for cytolysis and
      cytokine secretion, notably IFN-gamma, when encountering cognate antigen
      presented on defined numbers of cells. Our approach should facilitate
      determination of signatures of functional variance among individual effector CD8+
      T cells, including those from mucosal samples and those induced by vaccines.

PMID- 21965333
TI  - Accelerating axonal growth promotes motor recovery after peripheral nerve injury
      in mice.
AB  - Although peripheral nerves can regenerate after injury, proximal nerve injury in
      humans results in minimal restoration of motor function. One possible explanation
      for this is that injury-induced axonal growth is too slow. Heat shock protein 27
      (Hsp27) is a regeneration-associated protein that accelerates axonal growth in
      vitro. Here, we have shown that it can also do this in mice after peripheral
      nerve injury. While rapid motor and sensory recovery occurred in mice after a
      sciatic nerve crush injury, there was little return of motor function after
      sciatic nerve transection, because of the delay in motor axons reaching their
      target. This was not due to a failure of axonal growth, because injured motor
      axons eventually fully re-extended into muscles and sensory function returned;
      rather, it resulted from a lack of motor end plate reinnervation. Tg mice
      expressing high levels of Hsp27 demonstrated enhanced restoration of motor
      function after nerve transection/resuture by enabling motor synapse
      reinnervation, but only within 5 weeks of injury. In humans with peripheral nerve
      injuries, shorter wait times to decompression surgery led to improved functional
      recovery, and, while a return of sensation occurred in all patients, motor
      recovery was limited. Thus, absence of motor recovery after nerve damage may
      result from a failure of synapse reformation after prolonged denervation rather
      than a failure of axonal growth.

PMID- 21965334
TI  - Heterogeneity in breast cancer.
AB  - Breast cancer is a heterogeneous disease. There is a high degree of diversity
      between and within tumors as well as among cancer-bearing individuals, and all of
      these factors together determine the risk of disease progression and therapeutic
      resistance. Advances in technologies such as whole-genome sequencing and
      functional viability screens now allow us to analyze tumors at unprecedented
      depths. However, translating this increasing knowledge into clinical practice
      remains a challenge in part due to tumor evolution driven by the diversity of
      cancer cell populations and their microenvironment. The articles in this Review
      series discuss recent advances in our understanding of breast tumor
      heterogeneity, therapies tailored based on this knowledge, and future ways of
      assessing and treating heterogeneous tumors.

PMID- 21965335
TI  - Breast cancer - one term, many entities?
AB  - Breast cancer, rather than constituting a monolithic entity, comprises
      heterogeneous tumors with different clinical characteristics, disease courses,
      and responses to specific treatments. Tumor-intrinsic features, including
      classical histological and immunopathological classifications as well as more
      recently described molecular subtypes, separate breast tumors into multiple
      groups. Tumor-extrinsic features, including microenvironmental configuration,
      also have prognostic significance and further expand the list of tumor-defining
      variables. A better understanding of the features underlying heterogeneity, as
      well as of the mechanisms and consequences of their interactions, is essential to
      improve targeting of existing therapies and to develop novel agents addressing
      specific combinations of features.

PMID- 21965336
TI  - Targeted therapies for breast cancer.
AB  - In recent years the description of well-defined molecular subtypes of breast
      cancer, together with the identification of the driving genetic alterations and
      signaling pathways, has led to the clinical development of a number of successful
      molecular targeted agents. This is best exemplified in the subset of HER2
      amplified breast cancers, in which an increasing number of active agents are
      changing the natural history of this aggressive disease. Other targets are under
      exploration, and the clinical development of these agents will require a change
      from the current large, randomized trials in unselected patient populations to
      smaller trials in groups with a molecularly defined tumor type. In addition,
      combinatorial approaches that act on the secondary mutations and/or compensatory
      pathways in resistant tumors may markedly improve on the effects of targeted
      agents used alone.

PMID- 21965337
TI  - Breast cancer stem cells, cytokine networks, and the tumor microenvironment.
AB  - Many tumors, including breast cancer, are maintained by a subpopulation of cells
      that display stem cell properties, mediate metastasis, and contribute to
      treatment resistance. These cancer stem cells (CSCs) are regulated by complex
      interactions with the components of the tumor microenvironment - including
      mesenchymal stem cells, adipocytes, tumor associated fibroblasts, endothelial
      cells, and immune cells - through networks of cytokines and growth factors. Since
      these components have a direct influence on CSC properties, they represent
      attractive targets for therapeutic development.

PMID- 21965339
TI  - Introduction of Robert J. Lefkowitz.

PMID- 21965340
TI  - A tale of two callings.

PMID- 21965338
TI  - Insight into the heterogeneity of breast cancer through next-generation
      sequencing.
AB  - Rapid and sophisticated improvements in molecular analysis have allowed us to
      sequence whole human genomes as well as cancer genomes, and the findings suggest
      that we may be approaching the ability to individualize the diagnosis and
      treatment of cancer. This paradigmatic shift in approach will require clinicians
      and researchers to overcome several challenges including the huge spectrum of
      tumor types within a given cancer, as well as the cell-to-cell variations
      observed within tumors. This review discusses how next-generation sequencing of
      breast cancer genomes already reveals insight into tumor heterogeneity and how it
      can contribute to future breast cancer classification and management.

PMID- 21965341
TI  - Evolution of 5' untranslated region length and gene expression reprogramming in
      yeasts.
AB  - The sequences of the untranslated regions (UTRs) of mRNAs play important roles in
      posttranscriptional regulation, but whether a change in UTR length can
      significantly affect the regulation of gene expression is not clear. In this
      study, we examined the connection between UTR length and Expression Correlation
      with cytosolic ribosomal proteins (CRP) genes (ECC), which measures the level of
      expression similarity of a group of genes with CRP genes under various growth
      conditions. We used data from the aerobic fermentation yeast Saccharomyces
      cerevisiae and the aerobic respiration yeast Candida albicans. To reduce
      statistical fluctuations, we computed the ECC for the genes in a Gene Ontology
      (GO) functional group. We found that in both species, ECC is strongly correlated
      with the 5' UTR length but not with the 3' UTR length and that the 5' UTR length
      is evolutionarily better conserved than the 3' UTR length. Interestingly, we
      found 11 GO groups that have had a substantial increase in 5' UTR length in the
      S. cerevisiae lineage and that the length increase was associated with a
      substantial decrease in ECC. Moreover, 9 of the 11 GO groups of genes are
      involved in mitochondrial respiration function, whose expression reprogramming
      has been shown to be a major factor for the evolution of aerobic fermentation.
      Finally, we found that an increase in 5' UTR length may decrease the +1
      nucleosome occupancy. This study provides a new angle to understand the role of
      5' UTR in gene expression regulation and evolution.

PMID- 21965342
TI  - Evolution of antigen variation in the tick-borne pathogen Anaplasma
      phagocytophilum.
AB  - Anaplasma phagocytophilum is an obligately intracellular tick-transmitted
      bacterial pathogen of humans and other animals. During the course of infection,
      A. phagocytophilum utilizes gene conversion to shuffle ~100 functional
      pseudogenes into a single expression cassette of the msp2(p44) gene, which codes
      for the major surface antigen and major surface protein 2 (MSP2). The role and
      extent of msp2(p44) recombination, particularly in hosts that only experience
      acute infections, is not clear. In the present study, we explored patterns of
      recombination and expression of the msp2(p44) gene of A. phagocytophilum in a
      serially infected mouse model. Even though the bacterium was passed rapidly among
      mice, minimizing the opportunities for the host to develop adaptive immunity, we
      detected the emergence of 34 unique msp2(p44) expression cassette variants. The
      expression of msp2(p44) pseudogenes did not follow a consistent pattern among
      different groups of mice, although some pseudogenes were expressed more
      frequently than others. In addition, among 263 expressed pseudogenes, 3 mosaic
      sequences each consisting of 2 different pseudogenes were identified. Population
      genetic analysis showed that genetic diversity and subpopulation differentiation
      tended to increase over time until stationarity was reached but that the variance
      that was observed in allele (expressed pseudogene) frequency could occur by drift
      alone only if a high variance in bacterial reproduction could be assumed. These
      findings suggest that evolutionary forces influencing antigen variation in A.
      phagocytophilum may comprise random genetic drift as well as some innate but
      apparently nonpurifying selection prior to the strong frequency-dependent
      selection that occurs cyclically after hosts develop strong adaptive immunity.

PMID- 21965343
TI  - Exploring child car passenger safety practices in China: experience from a
      parental survey in Shanghai.
AB  - Little is known about child passenger safety practice in China. This study aims
      to describe child passenger seating and restraint practice in Shanghai.
      Information on 970 children enrolled in five randomly selected kindergartens in
      the Songjiang and Pudong districts of Shanghai was collected from a parental
      survey during 2008-2009. The adjusted rate ratios for optimal (rear-seated alone)
      versus suboptimal seating position (including front-seated or sitting in adult
      laps) and restraint use versus non-use of restraints among child passengers were
      evaluated using multivariate binomial regression. Suboptimal seating position
      (16.9%) and non-use of restraints (60.8%) was common among child passengers.
      Younger age (<=4 years) and having parents who are licensed drivers decreased the
      likelihood of being rear-seated alone; whereas having a tertiary-educated mother
      increased the likelihood of a child being seated optimally. Compared with
      unlicensed parents, guardian parents who have a driver's licence were more likely
      to use restraints for their child passengers. This study suggests restraint non
      use and suboptimal seating position are common for child passengers in the
      Songjiang and Pudong districts of Shanghai, and identifies risk factors
      influencing restraint use and seating position choice for child passengers. There
      is an urgent need to improve child passenger safety in China and these findings
      indicate potential targets for educational interventions in the absence of child
      restraint laws.

PMID- 21965345
TI  - Clinical impact of unclassified variants of the BRCA1 and BRCA2 genes.
AB  - Women who carry a pathogenic mutation in BRCA1 or BRCA2 have high risks of
      developing breast and ovarian cancers. The functional effect of many missense
      variants on BRCA1 and BRCA2 protein function is not known. Here, the authors
      construct a historical cohort of 4030 female first-degree relatives of 1345
      unselected patients with ovarian cancer who have been screened for BRCA1 and
      BRCA2 mutations. The authors compared the risks by the age of 80 years for all
      cancers combined in female first-degree relatives of women with a pathogenic
      mutation, women with a variant of unknown significance (unclassified variant) and
      non-carriers. The cumulative risk of cancer among the relatives of patients with
      a pathogenic mutation was much higher than the risk in relatives of non-carriers
      (50.2% vs 28.5%; HR=2.87, p<10(-4)). In contrast, the cumulative risk of cancer
      among relatives of patients carrying an unclassified variant was similar to the
      risk of cancer for relatives of non-carriers (27.6% vs 28.5%; HR=1.08, p=0.79).
      The authors used three different algorithms to predict the pathogenicity of
      unclassified variants and compared their penetrance with non-carriers. In this
      sample, only Align Grantham Variation Grantham Deviation appeared to predict
      penetrance based on first-degree relatives.

PMID- 21965344
TI  - Whole-genome duplications spurred the functional diversification of the globin
      gene superfamily in vertebrates.
AB  - It has been hypothesized that two successive rounds of whole-genome duplication
      (WGD) in the stem lineage of vertebrates provided genetic raw materials for the
      evolutionary innovation of many vertebrate-specific features. However, it has
      seldom been possible to trace such innovations to specific functional differences
      between paralogous gene products that derive from a WGD event. Here, we report
      genomic evidence for a direct link between WGD and key physiological innovations
      in the vertebrate oxygen transport system. Specifically, we demonstrate that key
      globin proteins that evolved specialized functions in different aspects of
      oxidative metabolism (hemoglobin, myoglobin, and cytoglobin) represent paralogous
      products of two WGD events in the vertebrate common ancestor. Analysis of
      conserved macrosynteny between the genomes of vertebrates and amphioxus
      (subphylum Cephalochordata) revealed that homologous chromosomal segments defined
      by myoglobin + globin-E, cytoglobin, and the alpha-globin gene cluster each
      descend from the same linkage group in the reconstructed proto-karyotype of the
      chordate common ancestor. The physiological division of labor between the oxygen
      transport function of hemoglobin and the oxygen storage function of myoglobin
      played a pivotal role in the evolution of aerobic energy metabolism, supporting
      the hypothesis that WGDs helped fuel key innovations in vertebrate evolution.

PMID- 21965346
TI  - Clinical validity of karyotyping for the diagnosis of chromosomal imbalance
      following array comparative genomic hybridisation.
AB  - BACKGROUND: Array comparative genomic hybridisation (aCGH) represents a major
      advance in the ability to detect chromosomal imbalances (CI). A recent meta
      analysis recommended aCGH for replacing karyotyping for patients with unexplained
      disabilities. However, favouring aCGH over karyotyping must be based on solid
      evidence due to the major implications of selecting a preferential diagnostic
      tool. METHODS AND RESULTS: A prospective study of 376 samples was conducted to
      assess the relevance of karyotyping after a first-tier aCGH in patients with
      unexplained disabilities. aCGH detected CI in 28.7% of the cases. Out of 376
      patients, 288 had undergone parallel karyotyping testing: 69.8% (201/288) showed
      similar results for both aCGH and karyotyping. For patients with a CI detected by
      aCGH, 7.9% (7/89) showed similar results for both aCGH and karyotyping. Among 20
      patients with abnormal karyotyping, 13 showed dissimilar results compared to aCGH
      analysis: 4 patients (1.4%) had balanced rearrangements and 9 patients (3.1%) had
      additional chromosomal anomalies unseen using aCGH. This rate of unseen
      chromosomal anomalies is far superior to the previously estimated 0.5-0.78%
      prevalence and affects 10.1% (9/89) of patients with CI detected by aCGH in the
      tested population. CONCLUSIONS: Since the clinical significance of CI identified
      by aCGH might be influenced by such discrepancies between the two methods, these
      may in turn have an impact on clinical diagnosis and patient counselling. It is
      proposed that each genetic laboratory should evaluate the relevance of
      karyotyping for all first-tier abnormal aCGH results in order to include the
      genomic (chromosomal) aspects of the aCGH findings in the diagnosis.

PMID- 21965347
TI  - Developmentally regulated IL6-type cytokines signal to germ cells in the human
      fetal ovary.
AB  - Fetal ovarian development and primordial follicle formation are imperative for
      adult fertility in the female. Data suggest the interleukin (IL)6-type cytokines,
      leukaemia inhibitory factor (LIF), IL6, oncostatin M (OSM) and ciliary
      neurotrophic factor (CNTF), are able to regulate the survival, proliferation and
      differentiation of fetal murine germ cells (GCs) in vivo and in vitro. We
      postulated that these factors may play a similar role during early human GC
      development and primordial follicle formation. To test this hypothesis, we have
      investigated the expression and regulation of IL6-type cytokines, using
      quantitative reverse transcription polymerase chain reaction and
      immunohistochemistry. Expression of transcripts encoding OSM increased
      significantly across the gestational range examined (8-20 weeks), while
      expression of IL6 increased specifically between the first (8-11 weeks) and early
      second (12-16 weeks) trimesters, co-incident with the initiation of meiosis. LIF
      and CNTF expression remained unchanged. Expression of the genes encoding the LIF
      and IL6 receptors, and their common signalling subunit gp130, was also found to
      be developmentally regulated, with expression increasing significantly with
      increasing gestation. LIF receptor and gp130 proteins localized exclusively to
      GCs, including oocytes in primordial follicles, indicating this cell type to be
      the sole target of IL6-type cytokine signalling in the human fetal ovary. These
      data establish that IL6-type cytokines and their receptors are expressed in the
      human fetal ovary and may directly influence GC development at multiple stages of
      maturation.

PMID- 21965348
TI  - Screening of the ryanodine 1 gene for malignant hyperthermia causative mutations
      by high resolution melt curve analysis.
AB  - BACKGROUND: A diagnosis of malignant hyperthermia (MH) can be determined by
      performing an in vitro (muscle) contracture test (IVCT) or by identifying a known
      MH causative mutation in the ryanodine receptor 1 gene (RYR1). Genetic diagnosis
      has an advantage over IVCT because it is less invasive. Direct sequencing of the
      very large RYR1 coding region (15.117 bases) is a laborious and expensive task.
      In this study, we applied the High Resolution Melting (HRM) curve analysis as a
      tool to screen the entire coding region of the gene. METHODS: Genomic DNA was
      extracted from peripheral blood samples in a cohort of 16 MH-susceptible patients
      diagnosed by the IVCT. The total coding region of RYR1 was divided and amplified
      by polymerase chain reaction in 131 DNA fragments and the melting profiles were
      compared with those of control samples. HRM curves were evaluated by Rotor-Gene Q
      software and visual inspection. Fragments showing aberrant melting profiles were
      sequenced to identify the underlying sequence variation. RESULTS: A subset of 520
      of 2520 DNA fragments (21%) showed significantly aberrant melting profiles. Upon
      sequencing, 131 known polymorphisms and 17 known or suspected mutations were
      found in 13 of 16 MH-susceptible patients (81%). Thus, the workload of sequencing
      was reduced by 79%. CONCLUSION: HRM curve analysis is a sensitive and cost
      effective tool for the identification of nucleotide sequence variants in complex
      genes such as the RYR1 gene.

PMID- 21965349
TI  - Pleth variability index to predict fluid responsiveness in colorectal surgery.
AB  - BACKGROUND: Goal-directed fluid therapy during major abdominal surgery may reduce
      postoperative morbidity. The Pleth Variability Index (PVI), derived from the
      pulse oximeter waveform, has been shown to be able to predict fluid
      responsiveness in a number of surgical circumstances. In the present study, we
      sought to determine whether PVI could predict fluid responsiveness in low-risk
      colorectal surgery patients who had fluid therapy guided by esophageal Doppler
      stroke volume measurements. METHODS: Twenty-five low-risk patients undergoing
      colorectal resection under general anesthesia were studied. Baseline values for
      esophageal Doppler stroke volume and PVI taken from finger and ear probes were
      compared with final values after (a) a 500-mL fluid bolus immediately after
      induction (steady state) and tracheal intubation before the start of the surgery,
      and (b) 250-mL boluses given in response to a decrease in stroke volume of 10%
      during surgery as measured by esophageal Doppler (dynamic). Patients were
      classified into responders and nonresponders based on a stroke volume increase of
      >10%. RESULTS: Baseline PVI at the finger was significantly higher in responders
      in both steady-state and intraoperative conditions. In steady state, PVI at both
      finger and earlobe had significant predictive ability of an increase in stroke
      volume: area under the curve for finger 0.96 (95% confidence interval [CI], 0.88
      1.00; P=0.011) and for earlobe 0.98 (95% CI, 0.93-1.00; P=0.008). In dynamic
      intraoperative conditions, PVI at the finger predicted increases in stroke
      volume, area under the curve 0.71 (95% CI, 0.57-0.85; P=0.006), but PVI at the
      earlobe had no predictive value. CONCLUSIONS: PVI measured at the finger may be
      able to predict fluid responsiveness during surgery in ventilated patients.

PMID- 21965350
TI  - Brief report: The sensitivity of motor responses for detecting catheter-nerve
      contact during ultrasound-guided femoral nerve blocks with stimulating catheters.
AB  - BACKGROUND: We determined the sensitivity of motor responses evoked by
      stimulating catheters in determining catheter-nerve contact using ultrasonography
      as reference. METHODS: Femoral nerves were contacted using stimulating catheters
      under ultrasonography scanning in 25 patients. The output current was increased
      from its minimum until quadriceps muscle contraction occurred. The sensitivity of
      the motor response in determining catheter-nerve contact was calculated using 0.5
      mA as current threshold. RESULTS: The current required for catheter stimulation
      to evoke a motor response ranged between 0.18 and 2.0 mA. Muscle contraction in
      response to 0.5 mA occurred in 16 of 25 subjects. The sensitivity of motor
      response for nerve stimulation was 64% (95% confidence interval: 0.43, 0.82).
      CONCLUSIONS: The absence of muscle responses at a stimulating current<=0.5 mA
      does not necessarily indicate the absence of catheter-nerve contact.

PMID- 21965351
TI  - Review article: Neurotoxicity of anesthetic drugs in the developing brain.
AB  - Anesthesia kills neurons in the brain of infantile animals, including primates,
      and causes permanent and progressive neurocognitive decline. The anesthesia
      community and regulatory authorities alike are concerned that is also true in
      humans. In this review, I summarize what we currently know about the risks of
      pediatric anesthesia to long-term cognitive function. If anesthesia is discovered
      to cause cognitive decline in humans, we need to know how to prevent and treat
      it. Prevention requires knowledge of the mechanisms of anesthesia-induced
      cognitive decline. This review gives an overview of some of the mechanisms that
      have been proposed for anesthesia-induced cognitive decline and discusses
      possible treatment options. If anesthesia induces cognitive decline in humans, we
      need to know what type and duration of anesthetic is safe, and which, if any, is
      not safe. This review discusses early results of comparative animal studies of
      anesthetic neurotoxicity. Until we know if and how pediatric anesthesia affects
      cognition in humans, a change in anesthetic practice would be premature, not
      guided by evidence of better alternatives, and therefore potentially dangerous.
      The SmartTots initiative jointly supported by the International Anesthesia
      Research Society and the Food and Drug Administration aims to fund research
      designed to shed light on these issues that are of high priority to the
      anesthesia community and the public alike and therefore deserves the full support
      of these interest groups.

PMID- 21965352
TI  - Review article: Preventive analgesia: quo vadimus?
AB  - The classic definition of preemptive analgesia requires 2 groups of patients to
      receive identical treatment before or after incision or surgery. The only
      difference between the 2 groups is the timing of administration of the drug
      relative to incision. The constraint to include a postincision or postsurgical
      treatment group is methodologically appealing, because in the presence of a
      positive result, it provides a window of time within which the observed effect
      occurred, and thus points to possible mechanisms underlying the effect: the
      classic view assumes that the intraoperative nociceptive barrage contributes to a
      greater extent to postoperative pain than does the postoperative nociceptive
      barrage. However, this view is too restrictive and narrow, in part because we
      know that sensitization is induced by factors other than the peripheral
      nociceptive barrage associated with incision and subsequent noxious
      intraoperative events. A broader approach to the prevention of postoperative pain
      has evolved that aims to minimize the deleterious immediate and long-term effects
      of noxious perioperative afferent input. The focus of preventive analgesia is not
      on the relative timing of analgesic or anesthetic interventions, but on
      attenuating the impact of the peripheral nociceptive barrage associated with
      noxious preoperative, intraoperative, and/or postoperative stimuli. These stimuli
      induce peripheral and central sensitization, which increase postoperative pain
      intensity and analgesic requirements. Preventing sensitization will reduce pain
      and analgesic requirements. Preventive analgesia is demonstrated when
      postoperative pain and/or analgesic use are reduced beyond the duration of action
      of the target drug, which we have defined as 5.5 half-lives of the target drug.
      This requirement ensures that the observed effects are not direct analgesic
      effects. In this article, we briefly review the history of preemptive analgesia
      and relate it to the broader concept of preventive analgesia. We highlight
      clinical trial designs and examples from the literature that distinguish
      preventive analgesia from preemptive analgesia and conclude with suggestions for
      future research.

PMID- 21965353
TI  - When right is right and when it's not: laterality in cardiac structures.

PMID- 21965354
TI  - Pharmacogenomics of beta-adrenergic receptor physiology and response to beta
      blockade.
AB  - Myocardial beta-adrenergic receptors (betaARs) are important in altering heart
      rate, inotropic state, and myocardial relaxation (lusitropy). The beta1AR and
      beta2AR stimulation increases cyclic adenosine monophosphate concentration with
      the net result of myocyte contraction, whereas beta3AR stimulation results in
      decreased inotropy. Downregulation of beta1ARs in heart failure, as well as an
      increased beta3AR activity and density, lead to decreased cyclic adenosine
      monophosphate production and reduced inotropy. The betaAR antagonists are
      commonly used in patients with coronary artery disease and heart failure;
      however, perioperative use of betaAR antagonists is controversial. Individual
      patient's response to beta-blocker therapy is an area of intensive research, and
      apart from pharmacokinetics, pharmacodynamics, and ethnic differences, genetic
      alterations have become more important in the last 20 years. The most common
      genetic variants in humans are single nucleotide polymorphisms (SNPs). There are
      2 clinically relevant SNPs for the beta1AR (Ser49Gly, Arg389Gly), 3 for the
      beta2AR (Arg16Gly, Gln27Glu, Thr164Ile), and 1 for the beta3AR (Trp64Arg).
      Although results are somewhat controversial, generally large datasets have the
      potential to show a relationship between betaAR SNPs and outcomes such as
      development and progression of heart failure, coronary artery disease, vascular
      reactivity, hypertension, asthma, obesity, and diabetes. Although betaAR SNPs may
      not directly cause disease, they appear to be risk factors for, and modifiers of,
      disease and the response to stress and drugs. In the perioperative setting, this
      has specifically been demonstrated for the Arg389Gly beta1AR polymorphism with
      which patients with the Gly variant had a higher incidence of adverse
      perioperative events. Knowing that genetic variants play an important role,
      perioperative medicine will likely change from simple therapeutic intervention to
      a more personalized way of adrenergic receptor modulation.

PMID- 21965355
TI  - Perioperative single dose ketorolac to prevent postoperative pain: a meta
      analysis of randomized trials.
AB  - BACKGROUND: Preventive analgesia using non-opioid analgesic strategies is
      recognized as a pathway to improve postoperative pain control while minimizing
      opioid-related side effects. Ketorolac is a nonsteroidal antiinflammatory drug
      frequently used to treat postoperative pain. However, the optimal dose and route
      of administration for systemic single dose ketorolac to prevent postoperative
      pain is not well defined. We performed a quantitative systematic review to
      evaluate the efficacy of a single dose of perioperative ketorolac on
      postoperative analgesia. METHODS: We followed the PRISMA statement guidelines. A
      wide search was performed to identify randomized controlled trials that evaluated
      the effects of a single dose of systemic ketorolac on postoperative pain and
      opioid consumption. Meta-analysis was performed using a random-effects model.
      Effects of ketorolac dose were evaluated by pooling studies into 30- and 60-mg
      dosage groups. Asymmetry of funnel plots was examined using Egger regression. The
      presence of heterogeneity was assessed by subgroup analysis according to the
      route of systemic administration (IV versus IM) and the time of drug
      administration (preincision versus postincision). RESULTS: Thirteen randomized
      clinical trials with 782 subjects were included. The weighted mean difference
      (95% confidence interval [CI]) of combined effects showed a difference for
      ketorolac over placebo for early pain at rest of -0.64 (-1.11 to -0.18) but not
      at late pain at rest, -0.29 (-0.88 to 0.29) summary point (0-10 scale). Opioid
      consumption was decreased by the 60-mg dose, with a mean (95% CI) IV morphine
      equivalent consumption of -1.64 mg (-2.90 to -0.37 mg). The opioid-sparing
      effects of ketorolac compared with placebo were greater when the drug was
      administered IM compared with when the drug was administered IV, with a mean
      difference (95% CI) IV morphine equivalent consumption of -2.13 mg (-4.1 to -0.21
      mg). Postoperative nausea and vomiting were reduced by the 60-mg dose, with an
      odds ratio (95% CI) of 0.49 (0.29-0.81). CONCLUSIONS: Single dose systemic
      ketorolac is an effective adjunct in multimodal regimens to reduce postoperative
      pain. Improved postoperative analgesia achieved with ketorolac was also
      accompanied by a reduction in postoperative nausea and vomiting. The 60-mg dose
      offers significant benefits but there is a lack of current evidence that the 30
      mg dose offers significant benefits on postoperative pain outcomes.

PMID- 21965356
TI  - Brief preoperative smoking abstinence: is there a dilemma?
AB  - The concern that stopping smoking shortly (<8 weeks) before surgery increases
      postoperative pulmonary complications poses a barrier to tobacco use
      interventions in surgical patients. We show how this concern arose from a
      misinterpretation of initial studies and has remained in the medical literature
      despite the accumulation of later evidence. The persistence of unsubstantiated
      concepts is not uncommon and can have a significant impact on medical practice.
      Although it may take several weeks to derive pulmonary benefit from quitting,
      fear of an increase in pulmonary complications should not be a barrier for
      clinicians to help their patients quit smoking at any time before surgery.

PMID- 21965357
TI  - High thoracic/cervical epidural blood patch for spontaneous cerebrospinal fluid
      leak: a new challenge for anesthesiologists.
AB  - Spontaneous cerebral spinal fluid leakage is increasingly recognized as a cause
      of headache due to low intracranial pressure. The site of leakage can be
      identified with radionuclide cisternography, and anesthesiologists are
      increasingly requested to provide epidural blood patch for their management. This
      series of case reports demonstrates some of the issues relating to the management
      of this condition.

PMID- 21965358
TI  - Free-floating intracardiac mass after cardiopulmonary bypass for aortic valve
      replacement.

PMID- 21965359
TI  - Application of the Rasch model to develop a simplified version of a
      multiattribute utility measurement on attitude toward labor epidural analgesia.
AB  - BACKGROUND: Valid and reliable measures based on health behavior theory, such as
      multiattribute utility decision theory, are essential to elucidate complex
      relationships between psychological factors and labor pain. In this study we
      aimed to use Rasch analysis to simplify a previously developed 20-item
      multidimensional questionnaire on attitude toward labor epidural analgesia using
      multiattribute utility theory. METHODS: The Rasch analysis was performed to
      condense item selection categories, to exclude misfit items and persons, and to
      generate a unidimensional attitude toward labor epidural analgesia (ATLEA) score.
      Item characteristics and thresholds of rating categories in the questionnaire
      were also estimated. Reliability and empirical validity of the simplified version
      were further compared with those of the full version. RESULTS: One hundred sixty
      seven postpartum women completed the questionnaire. The original 10 rating scale
      categories were combined to make 4 without compromising reliability. Three
      respondents and 11 items were excluded because of misfit. Reliability indices of
      the simplified and full versions were 0.68 and 0.74, respectively. The
      correlation coefficient between ATLEA scores from the simplified and full
      versions was 0.89. Empirical validity values of ATLEA scores from the simplified
      and full versions for labor epidural analgesia decision, as assessed by area
      under the receiver operating characteristic curves, were 0.80 and 0.81,
      respectively. CONCLUSIONS: We demonstrated application of the Rasch analysis to
      simplifying a multiattribute utility questionnaire without compromising
      reliability. Further study is necessary to determine whether the simplified
      questionnaire is valid for use in clinical practice.

PMID- 21965360
TI  - Distal tourniquet or leg position after injection enhances the efficacy of
      sciatic nerve blockade by the popliteal approach.
AB  - BACKGROUND: In this study, we hypothesized that leg positioning and distal
      tourniquet application, when compared with neutral positioning of the leg, alters
      the efficacy of sciatic nerve block performed by the double-stimulation
      technique. METHODS: Ninety randomized, consecutive, ASA physical status I to III
      patients undergoing foot and ankle surgery with a popliteal fossa block (using a
      double-stimulation technique with the patient in prone position) were
      prospectively studied. Patients were randomized to have the blocked leg either
      kept in a neutral position immediately after the patient was turned supine (group
      1), flexed 45 degrees at the thigh and maintained in that position for 15 minutes
      (group 2), or have a distal tourniquet applied with the leg in a neutral position
      and inflated during injection of the local anesthetic with the patient supine
      (group 3). A standardized local anesthetic mixture containing 15 mL of 2%
      prilocaine and 15 mL of 0.5% levobupivacaine was used in all study groups.
      RESULTS: The onset times for sensory and motor blocks were shorter, and the time
      to recovery of blocks was longer, postprocedure in both group 2 and 3.
      CONCLUSIONS: Similar beneficial effects might be reached with the application of
      a distal tourniquet during injection or elevating the patient's leg turned supine
      immediately after sciatic nerve block with a popliteal approach by a double
      injection technique. We suggest that using the leg-up position or application of
      a distal tourniquet for sciatic nerve block may lead to a more proximal
      distribution of the local anesthetic and may result in a faster onset of sensory
      and motor blocks as well as longer duration of blockade.

PMID- 21965361
TI  - The Bainbridge and the "reverse" Bainbridge reflexes: history, physiology, and
      clinical relevance.
AB  - Francis A. Bainbridge demonstrated in 1915 that an infusion of saline or blood
      into the jugular vein of the anesthetized dog produced tachycardia. His findings
      after transection of the cardiac autonomic nerve supply and injection of the
      cholinergic blocking drug atropine demonstrated that the tachycardia was reflex
      in origin, with the vagus nerves constituting the afferent limb and a withdrawal
      of vagal tone the primary efferent limb. Subsequent investigators demonstrated
      that the increase in venous return was detected by stretch receptors in the right
      and left atria. In the 1980s, it was shown convincingly that the Bainbridge
      reflex was present in primates, including humans, but that the reflex was much
      less prominent than in the dog. This difference may be due to a more dominant
      arterial baroreceptor reflex in humans. A "reverse" Bainbridge reflex has been
      proposed to explain the decreases in heart rate observed under conditions in
      which venous return is reduced, such as during spinal and epidural anesthesia,
      controlled hypotension, and severe hemorrhage. The Bainbridge reflex is invoked
      throughout the anesthesia literature to describe the effect of changes in venous
      return on heart rate in patients in the surgical and critical care settings, but
      a critical analysis of the experimental and clinical evidence is lacking. Our
      main objectives in this review are to summarize the history of the Bainbridge
      reflex, to describe its anatomy and physiology, and to discuss the evidence for
      and against it having an influence on heart rate changes observed clinically. The
      interaction of the Bainbridge reflex with the arterial baroreceptor and Bezold
      Jarisch reflexes is discussed.

PMID- 21965362
TI  - Review article: closed-loop systems in anesthesia: is there a potential for
      closed-loop fluid management and hemodynamic optimization?
AB  - Closed-loop (automated) controllers are encountered in all aspects of modern life
      in applications ranging from air-conditioning to spaceflight. Although these
      systems are virtually ubiquitous, they are infrequently used in anesthesiology
      because of the complexity of physiologic systems and the difficulty in obtaining
      reliable and valid feedback data from the patient. Despite these challenges,
      closed-loop systems are being increasingly studied and improved for medical use.
      Two recent developments have made fluid administration a candidate for closed
      loop control. First, the further description and development of dynamic
      predictors of fluid responsiveness provides a strong parameter for use as a
      control variable to guide fluid administration. Second, rapid advances in
      noninvasive monitoring of cardiac output and other hemodynamic variables make
      goal-directed therapy applicable for a wide range of patients in a variety of
      clinical care settings. In this article, we review the history of closed-loop
      controllers in clinical care, discuss the current understanding and limitations
      of the dynamic predictors of fluid responsiveness, and examine how these
      variables might be incorporated into a closed-loop fluid administration system.

PMID- 21965363
TI  - Inhibition of KCC2 in mouse spinal cord neurons leads to hypersensitivity to
      thermal stimulation.
AB  - BACKGROUND: KCC2, a neuronal-specific K-Cl cotransporter, is involved in pain
      perception physiology through its effects on postsynaptic inhibition in spinal
      cord neurons. We injected a newly identified, highly potent and selective
      inhibitor of KCC2 (D4), an inactive structural variant (D4.14), and the Na-K-2Cl
      cotransporter (NKCC1) inhibitor, bumetanide, into the intrathecal space of mice
      to measure their effect on heat-evoked nociceptive responses. METHODS:
      Commercially available intrathecal catheters were modified and surgically placed
      into 2 cohorts of 10 mice. After recovery from the procedure, the mice were
      injected with D4, D4.14, and bumetanide through this catheter. Nociceptive
      measurements (hotplate assay, tail flick assay) were performed after injection of
      each of the test drugs and compared with vehicle controls. RESULTS: Two mice in
      each cohort were omitted because of postprocedure complications. There was a
      statistically significant decrease (P < 0.01) in withdrawal latency after
      injection of the active KCC2 inhibitor but not after injection of the inactive
      compound (P = 0.78), as measured by hotplate assay at 55 degrees C. Injection of
      bumetanide significantly increased withdrawal latency (P = 0.02) at the same
      temperature. These results were confirmed using tail flick assays performed at 49
      degrees C. CONCLUSIONS: Inhibition of KCC2 by D4 led to decreased heat-evoked
      withdrawal latency in mice, as measured by hotplate and tail flick assays,
      whereas inhibition of NKCC1 by bumetanide resulted in increased response
      latencies to heat stimuli as measured by both of these nociceptive tests.

PMID- 21965365
TI  - Operation timing and 30-day mortality after elective general surgery.
AB  - BACKGROUND: Human factors such as fatigue, circadian rhythms, scheduling, and
      staffing may have an impact on patient care over the course of a day across all
      medical specialties. Research by the transportation industry concludes that human
      performance is degraded by shift work, circadian rhythm disturbances, and
      prolonged duty. We investigated whether the timing of general surgery
      (specifically, increasing time of day, increasing day of week, July/August cases
      versus other months), and moon phase is independently related to 30-day
      mortality. A secondary outcome of composite in-hospital complications was also
      evaluated. METHODS: The binary outcomes of 32,001 elective general surgical
      patients at the Cleveland Clinic between January 2005 and September 2010 were
      analyzed according to the hour of the day (6 am to 7 pm), day of the workweek,
      month of the year, and moon phase in which the surgery started. Thirty-day
      mortality was modeled as a binary endpoint using a multivariable logistic
      regression, adjusting for a risk stratification index based on International
      Classification of Diseases (9(th) rev.) codes. RESULTS: The adjusted odds ratio
      ([Bonferroni-adjusted 95% CI]) associated with a relative increase in time of day
      of 4 h was 1.23 [0.91, 1.67], P = 0.09. Similarly, no association was found for
      day of week (0.99 [0.83, 1.17]) for a relative increase of 1 day, P = 0.85.
      Mortality was not significantly more frequent in July and August than in other
      months (adjusted odds ratio = 0.72 [0.36, 1.43], P = 0.22). Moon phase was not
      significantly related to mortality (P = 0.72). There were also no significant
      time-dependent differences in composite complications. CONCLUSIONS: Elective
      general surgery appears to be comparably safe at any time of the workday, any day
      of the workweek, and in any month of the year.

PMID- 21965364
TI  - In vivo and in vitro pharmacological studies of methoxycarbonyl-carboetomidate.
AB  - BACKGROUND: We previously developed 2 etomidate analogs that retain etomidate's
      favorable hemodynamic properties but whose adrenocortical effects are reduced in
      duration or magnitude. Methoxycarbonyl (MOC)-etomidate is rapidly metabolized and
      ultrashort acting whereas (R)-ethyl 1-(1-phenylethyl)-1H-pyrrole-2-carboxylate
      (carboetomidate) does not potently inhibit 11beta-hydroxylase. We hypothesized
      that MOC-etomidate's labile ester could be incorporated into carboetomidate to
      produce a new agent that possesses favorable properties individually found in
      each agent. We describe the synthesis and pharmacology of MOC-(R)-ethyl 1-(1
      phenylethyl)-1H-pyrrole-2-carboxylate (MOC-carboetomidate), a "soft" analog of
      carboetomidate. METHODS: MOC-carboetomidate's octanol:water partition coefficient
      was determined chromatographically and compared with those of etomidate,
      carboetomidate, and MOC-etomidate. MOC-carboetomidate's 50% effective
      concentration (EC(50)) and 50% effective dose for loss of righting reflexes
      (LORR) were measured in tadpoles and rats, respectively. Its effect on gamma
      aminobutyric acid A (GABA(A)) receptor function was assessed using 2
      microelectrode voltage clamp electrophysiological techniques and its metabolic
      stability was determined in pooled rat blood using high performance liquid
      chromatography. Its duration of action and effects on arterial blood pressure and
      adrenocortical function were assessed in rats. RESULTS: MOC-carboetomidate's
      octanol:water partition coefficient was 3300 +/- 280, whereas those for
      etomidate, carboetomidate, and MOC-etomidate were 800 +/- 180, 15,000 +/- 3700,
      and 190 +/- 25, respectively. MOC-carboetomidate's EC(50) for LORR in tadpoles
      was 9 +/- 1 MUM and its EC(50) for LORR in rats was 13 +/- 5 mg/kg. At 13 MUM,
      MOC-carboetomidate enhanced GABA(A) receptor currents by 400% +/- 100%. Its
      metabolic half-life in pooled rat blood was 1.3 min. The slope of a plot of the
      duration of LORR in rats versus the logarithm of the hypnotic dose was
      significantly shallower for MOC-carboetomidate than for carboetomidate (4 +/- 1
      vs 15 +/- 3, respectively; P = 0.0004123). At hypnotic doses, the effects of MOC
      carboetomidate on arterial blood pressure and adrenocortical function were not
      significantly different from those of vehicle alone. CONCLUSIONS: MOC
      carboetomidate is a GABA(A) receptor modulator with potent hypnotic activity that
      is more rapidly metabolized and cleared from the brain than carboetomidate,
      maintains hemodynamic stability similar to carboetomidate, and does not suppress
      adrenocortical function.

PMID- 21965366
TI  - Case report: automated machine checkout leaves an internal gas leak undetected:
      the need for complete checkout procedures.
AB  - We report a complete internal fresh gas flow disconnect within a Drager Fabius GS
      anesthesia machine without any alarms being triggered. This was undetected
      primarily because of an incomplete machine checkout in which the step of ensuring
      proper gas flows by using a "test lung" was omitted. Machine-specific factors,
      however, also contributed to prevent diagnosis: (1) the machine passed its leak
      test because the flowmeter bobbin (i.e., floating ball) sealed the flowmeter when
      back pressure was applied; (2) the mechanical ventilator entrains room air, thus
      functioning in the absence of fresh gas flow; and (3) the electronic flow sensors
      functioned "appropriately" because the leak was downstream. Despite the advent of
      highly automated machines, manual checkout procedures remain crucial to
      minimizing undiagnosed failures.

PMID- 21965368
TI  - Enhancing the relative safety of intentional or unintentional intrathecal
      methylprednisolone administration by removing polyethylene glycol.
AB  - BACKGROUND: Previous studies have shown that intrathecal methylprednisolone is a
      very effective treatment for postherpetic neuralgia. However, widespread use of
      intrathecal methylprednisolone is limited by the presence of polyethylene glycol
      (PEG) as a preservative in the commercial formulation. In this study, we are
      proposing a method to reduce the concentration of PEG in the methylprednisolone
      acetate (MPA) suspension by inverting a vial before sterilely aspirating the
      contents into a syringe for subsequent injection. The purpose of this brief study
      was to precisely quantify the concentration of PEG in the MPA suspension.
      METHODS: Single-dose vials containing 80 mg of MPA suspension were inverted to
      promote partition of the PEG away from the steroid component. After achieving 2
      phases, we carefully extracted and aspirated only the steroid component. We kept
      the vials inverted for different time points (from 0 to 480 minutes), and we
      measured the concentration of PEG and methylprednisolone by using liquid
      chromatography and mass spectrometry. We also measured the pH of samples by using
      the pH meter for small samples. RESULTS: The 1-way analysis of variance with post
      hoc analysis and Bonferroni correction showed statistically significant
      differences (P < 0.0001) between baseline concentrations and concentrations after
      inverting the vials for different times. We removed a minimum of 78% of PEG (the
      Bonferroni-corrected lower confidence limit for overall reduction in PEG) by
      keeping the vials inverted from 2 to 4 hours, and the average amount removed was
      85% per vial. However, we did not change the concentration of methylprednisolone
      or the pH of the solution. CONCLUSIONS: We believe that by decreasing the PEG
      concentration using our method, MPA-related complications will potentially be
      reduced, and this should be considered in patients with postherpetic neuralgia
      refractory to other treatments who might be candidates for repeated intrathecal
      injections.

PMID- 21965367
TI  - 2-Deoxy-D-glucose attenuates isoflurane-induced cytotoxicity in an in vitro cell
      culture model of H4 human neuroglioma cells.
AB  - BACKGROUND: beta-Amyloid protein (Abeta) accumulation and caspase activation have
      been shown to contribute to Alzheimer disease neuropathogenesis. Abeta is
      produced from amyloid precursor protein through proteolytic processing by
      aspartyl protease beta-site amyloid precursor protein-cleaving enzyme (BACE). The
      inhaled anesthetic isoflurane has been shown to induce caspase activation and
      increase levels of BACE and Abeta. However, the underlying mechanisms and
      interventions of the isoflurane-induced neurotoxicity remain largely to be
      determined. The glucose analog 2-deoxy-d-glucose (2-DG) has neuroprotective
      effects. Therefore, we sought to determine whether 2-DG can reduce caspase-3
      activation and the increase in the levels of BACE and reactive oxygen species
      (ROS) induced by isoflurane. METHODS: H4 human neuroglioma cells were treated
      with saline or 2-DG (5 mM) for 1 hour followed by a control condition or 2%
      isoflurane for 6 hours. The levels of caspase-3 cleavage (activation), BACE,
      cytosolic calcium, and ROS were determined. Two-way analysis of variance was used
      to assess the interactions of 2-DG and isoflurane on caspase-3 activation, and
      levels of BACE and ROS. RESULTS: In H4 human neuroglioma cells, 2-DG reduced the
      caspase-3 activation (477% vs 186%, F = 8.68; P = 0.019) and the increase in BACE
      levels (345% vs 123%, F = 42.24; P = 0.0002) induced by isoflurane. 2-DG
      decreased the levels of cytosolic calcium and ROS (100% vs 66%, F = 1.94; P =
      0.014). CONCLUSIONS: These results suggest that 2-DG may decrease oxidative
      stress and increase cytosolic calcium levels, thus attenuating isoflurane-induced
      neurotoxicity.

PMID- 21965369
TI  - Automatic computerized endotracheal tube position verification: an animal model
      evaluation.
AB  - BACKGROUND: Improper endotracheal tube positioning carries a high risk for
      morbidity and mortality; verification and confirmation of correct placement is
      necessary. We propose a computer-automated identification of endotracheal tube
      positioning using image analysis. The end product will not retain a monitor;
      rather, the acquired image will be automatically analyzed by a mini electronic
      processor. METHODS: An algorithm that automatically analyzes images has been
      developed: it classifies images into esophagus, trachea, and carina. Image
      processing includes converting the image to grayscale and extracting and
      classifying into 1 class, on the basis of similarity to pretrained patterns. A
      prototypical video sensor mounted on an intubating stylet has also been
      assembled. This stylet was introduced into 10 bovine throats, and video images
      were gathered. Videos were analyzed and classified as carina, trachea, or
      esophagus. The videos were then introduced to the new algorithm. In each test
      cycle, 9 videos were used to train the algorithm, and the 10th was used as a
      benchmark. This procedure was repeated 10 times so that each video was used 9
      times for teaching and 1 time for testing. RESULTS: Ten videos were recorded, of
      which 1600 images were extracted (trachea: 490 images; carina: 550 images; and
      esophagus: 560 images). Only 1 esophageal image was classified as trachea (false
      positive 0.001%). Two carinal images and 22 tracheal images were recognized as
      esophagus (false negative 0.041%), sensitivity 0.98 and specificity 0.99. Twenty
      images of the carina were identified as trachea, and 25 images of the trachea
      were identified as the carina (false positive 0.045%, false negative 0.041%,
      sensitivity 0.96 and specificity 0.95). CONCLUSION: A potential tube position
      verification system was assessed. High accuracy of the analysis algorithm was
      shown using nonperfused biological tissue, justifying further research.

PMID- 21965370
TI  - The current status of continuous noninvasive measurement of total, carboxy, and
      methemoglobin concentration.
AB  - Intraoperative early detection of anemia, identifying toxic levels of
      carboxyhemoglobin after carbon monoxide exposure and titrating drug dosage to
      prevent toxic levels of methemoglobin are important goals. The pulse oximeter
      works by illuminating light into the tissue and sensing the amount of light
      absorbed. The same methodology is used by laboratory hemoglobinometers to measure
      hemoglobin concentration. Because both devices work in the same way, efforts were
      made to modify the pulse oximeter to also measure hemoglobin concentration.
      Currently there are 2 commercial pulse oximeters (Masimo Rainbow SET and OrSense
      NBM-200MP) that measure total hemoglobin concentration and one (Masimo) that also
      measures methemoglobin and carboxyhemoglobin. In this review, we describe the
      peer-reviewed literature addressing the accuracy of these monitors.

PMID- 21965371
TI  - Fibrinogen and hemostasis: a primary hemostatic target for the management of
      acquired bleeding.
AB  - Fibrinogen plays several key roles in the maintenance of hemostasis. Its cleavage
      by thrombin and subsequent polymerization to form fibrin strands provides the
      structural network required for effective clot formation. During cases of acute
      blood loss, attempts to maintain circulating volume and tissue perfusion often
      involve the infusion of crystalloids, colloids, and red blood cells.
      Intravascular volume resuscitation, although vital, frequently results in
      dilution of the remaining clotting factors and onset of dilutional coagulopathy.
      In such cases, fibrinogen is the first coagulation factor to decrease to
      critically low levels. There currently is a lack of awareness among physicians
      regarding the significance of fibrinogen during acute bleeding and, at many
      centers, fibrinogen is not monitored routinely during treatment. We reviewed
      current studies that demonstrate the importance of considering fibrinogen
      replacement during the treatment of acquired bleeding across clinical settings.
      If depleted, the supplementation of fibrinogen is key for the rescue and
      maintenance of hemostatic function; however, the threshold at which such
      intervention should be triggered is currently poorly defined. Although
      traditionally performed via administration of fresh frozen plasma or
      cryoprecipitate, the use of lyophilized fibrinogen (concentrate) is becoming more
      prevalent in some countries. Recent reports relating to the efficacy of
      fibrinogen concentrate suggest that it is a viable alternative to traditional
      hemostatic approaches, which should be considered. The prospective study of
      fibrinogen supplementation in acquired bleeding is needed to accurately assess
      the range of clinical settings in which this management strategy is appropriate,
      the most effective method of supplementation and a comprehensive safety profile
      of fibrinogen concentrate used for such an approach.

PMID- 21965372
TI  - Continuous noninvasive hemoglobin monitoring during complex spine surgery.
AB  - BACKGROUND: Monitoring hemoglobin levels in the operating room currently requires
      repeated blood draws, several steps, and a variable time delay to receive
      results. Consequently, blood transfusion management decisions may be delayed or
      made before hemoglobin results become available. The ability to measure
      hemoglobin continuously and noninvasively may enable a more rapid assessment of a
      patient's condition and more appropriate blood management. A new technology,
      Pulse CO-Oximetry, provides a continuous, noninvasive estimate of hemoglobin
      concentration (SpHb) from a sensor placed on the finger. We evaluated the
      accuracy of SpHb compared with laboratory CO-Oximetry measurements of total
      hemoglobin (tHb) during complex spine procedures in patients at high risk for
      blood loss. METHODS: Patients eligible for the study were undergoing complex
      spine surgery with planned invasive arterial or central venous monitoring and
      hourly blood draws for hemoglobin measurement. During each surgery, blood samples
      were obtained hourly (or more often if clinically indicated) and analyzed by the
      central laboratory with CO-Oximetry, a standard method of hemoglobin measurement
      in many hospitals. The tHb measurements were compared with SpHb obtained at the
      time of the blood draw. RESULTS: Twenty-nine patients were included in the study.
      The tHb values ranged from 6.9 to 13.9 g/dL, and the SpHb values ranged from 6.9
      to 13.4 g/dL. A total of 186 data pairs (tHb/SpHb) were analyzed; after removal
      of SpHb readings with low signal quality, the bias (defined as the difference
      between SpHb and tHb) and precision (defined as 1 SD of the bias) were -0.1 g/dL
      +/- 1.0 g/dL for the remaining 130 data pairs. Bland-Altman analysis showed good
      agreement of SpHb to tHb values over the range of values; limits of agreement
      were -2.0 to 1.8 g/dL. The absolute bias and precision were 0.8 +/- 0.6 g/dL.
      CONCLUSIONS: Continuous, noninvasive hemoglobin measurement via Pulse CO-Oximetry
      demonstrated clinically acceptable accuracy of hemoglobin measurement within 1.5
      g/dL compared with a standard laboratory reference device when used during
      complex spine surgery. This technology may provide more timely information on
      hemoglobin status than intermittent blood sample analysis and thus has the
      potential to improve blood management during surgery.

PMID- 21965373
TI  - Forced-air warming does not worsen air quality in laminar flow operating rooms.
AB  - BACKGROUND: Warm air released by forced-air covers could theoretically disturb
      laminar airflow in operating rooms. We thus tested the hypothesis that laminar
      flow performance remains well within rigorous and objective standards during
      forced-air warming. METHODS: We evaluated air quality in 2 laminar flow operating
      rooms using a volunteer "patient" and heated manikin "surgeons." Reduction in
      tracer background particle counts near the site of a putative surgical incision
      was evaluated as specified by the rigorous DIN 1946-4:2008-12 standard. Results
      were confirmed using smoke as a visual tracer. RESULTS: Background tracer
      particle concentrations were reduced 4 to 5 log by the laminar flow system, and
      there were no statistically significant or clinically important differences with
      a forced-air blower set to off, ambient air, and high temperature. All values
      remained well within the requirements of the DIN 1946-4:2008-12 standard.
      Activation of a forced-air warming system did not create an upward draft or
      interfere with normal and effective function of the laminar flow process.
      CONCLUSIONS: Our results, based on quantitative performance testing methods,
      indicate that forced-air warming does not reduce operating room air quality
      during laminar flow ventilation. Because there is no decrement in laminar flow
      performance, forced-air warming remains an appropriate intraoperative warming
      method when laminar flow is used.

PMID- 21965374
TI  - Cardiovascular effects of dexmedetomidine sedation in children.
AB  - BACKGROUND: Dexmedetomidine (DEX) affects heart rate (HR), mean arterial blood
      pressure, cardiac index (CI), stroke index (SI), and systemic vascular resistance
      index (SVRI) in adults. In this study we sought to determine whether similar
      effects occur in children undergoing DEX sedation. METHODS: Hemodynamic changes
      in children were followed during IV DEX sedation for radiological procedures. One
      group of 8 patients (DEX-brief) received a bolus (2 mcg/kg bolus over 10 minutes)
      and completed the procedure within 10 minutes. The second group of 9 patients
      (DEX-prolong) received the bolus plus additional DEX as needed to maintain
      sedation for procedures lasting longer than 10 minutes (additional 1 mcg/kg/hr
      infusion with second bolus if needed). CI, SI, and SVRI were measured using a
      continuous noninvasive cardiac output monitor. Changes in hemodynamic variables
      at minutes 10, 20, and discharge (time at which patient achieved Aldrete Score
      >=9) were compared to baseline by repeated measures ANOVA with effect sizes
      reported as mean [95% confidence interval]. RESULTS: Data were obtained during 8
      DEX-brief and 9 DEX-prolong procedures. In DEX-brief, HR and CI decreased (18.9
      [2.3 to 35.5] bpm and 0.74 [0.15 to 1.33] L/min/m(2); respectively) at T1. There
      was no change in any other hemodynamic variables and all hemodynamic variables
      returned to baseline at recovery. In DEX-prolong, both HR and CI remained
      decreased (24.0 [8.3 to 39.6] bpm, 1.51 [0.95 to 2.06] L/min/m(2); respectively)
      at recovery. In addition, SI was decreased (8.01 [1.71 to 14.31] mL/m(2)) and
      SVRI was increased (776.0 [271.9 to 1280.4] dynes-sec/cm(5)/m(2)) at recovery in
      the DEX-prolong group. There were no significant changes in mean arterial blood
      pressure in either group. CONCLUSION: DEX decreases CI in children and has a
      cumulative effect. For patients undergoing prolonged procedures HR and CI
      remained decreased at the time of discharge together with a decrease in SI and an
      increase in SVRI.

PMID- 21965375
TI  - Decreased miR-29 suppresses myogenesis in CKD.
AB  - The mechanisms underlying the muscle wasting that accompanies CKD are not well
      understood. Animal models suggest that impaired differentiation of muscle
      progenitor cells may contribute. Expression of the myogenesis-suppressing
      transcription factor Ying Yang-1 increases in muscle of animals with CKD, but the
      mechanism underlying this increased expression is unknown. Here, we examined a
      profile of microRNAs in muscles from mice with CKD and observed downregulation of
      both microRNA-29a (miR-29a) and miR-29b. Because miR-29 has a complementary
      sequence to the 3'-untranslated region of Ying Yang-1 mRNA, a decrease in miR-29
      could increase Ying Yang-1. We used adenovirus-mediated gene transfer to express
      miR-29 in C2C12 myoblasts and measured its effect on both Ying Yang-1 and
      myoblast differentiation. An increase in miR-29 decreased the abundance of Ying
      Yang-1 and improved the differentiation of myoblasts into myotubes. Similarly,
      using myoblasts isolated from muscles of mice with CKD, an increase in miR-29
      improved differentiation of muscle progenitor cells into myotubes. In conclusion,
      CKD suppresses miR-29 in muscle, which leads to higher expression of the
      transcription factor Ying Yang-1, thereby suppressing myogenesis. These data
      suggest a potential mechanism for the impaired muscle cell differentiation
      associated with CKD.

PMID- 21965376
TI  - Cells derived from young bone marrow alleviate renal aging.
AB  - Bone marrow-derived stem cells may modulate renal injury, but the effects may
      depend on the age of the stem cells. Here we investigated whether bone marrow
      from young mice attenuates renal aging in old mice. We radiated female 12-mo-old
      129SvJ mice and reconstituted them with bone marrow cells (BMC) from either 8-wk
      old (young-to-old) or 12-mo-old (old-to-old) male mice. Transfer of young BMC
      resulted in markedly decreased deposition of collagen IV in the mesangium and
      less beta-galactosidase staining, an indicator of cell senescence. These changes
      paralleled reduced expression of plasminogen activator inhibitor-1 (PAI-1), PDGF
      B (PDGF-B), the transdifferentiation marker fibroblast-specific protein-1 (FSP
      1), and senescence-associated p16 and p21. Tubulointerstitial and glomerular
      cells derived from the transplanted BMC did not show beta-galactosidase activity,
      but after 6 mo, there were more FSP-1-expressing bone marrow-derived cells in old
      to-old mice compared with young-to-old mice. Young-to-old mice also exhibited
      higher expression of the anti-aging gene Klotho and less phosphorylation of IGF-1
      receptor beta. Taken together, these data suggest that young bone marrow-derived
      cells can alleviate renal aging in old mice. Direct parenchymal reconstitution by
      stem cells, paracrine effects from adjacent cells, and circulating anti-aging
      molecules may mediate the aging of the kidney.

PMID- 21965377
TI  - Estimated GFR, albuminuria, and complications of chronic kidney disease.
AB  - Higher levels of albuminuria associate with increased risk for adverse outcomes
      independent of estimated GFR (eGFR), but whether albuminuria also associates with
      concurrent complications specific to chronic kidney disease (CKD) is unknown.
      Here, we assessed the association of spot albumin-to-creatinine ratio with
      anemia, acidosis, hyperphosphatemia, hypoalbuminemia, hyperparathyroidism, and
      hypertension among 30,528 adult participants in NHANES 1988-1994 and 1999-2006.
      After multivariable adjustment including eGFR, higher albumin-to-creatinine
      ratios associated with anemia, acidosis, hypoalbuminemia, hyperparathyroidism,
      and hypertension but only weakly associated with acidosis and anemia.
      Furthermore, the associations between albumin-to-creatinine ratio and both anemia
      and acidosis were not consistent across eGFR strata. Higher albumin-to-creatinine
      ratio levels did not associate with hyperphosphatemia. Lower eGFR associated with
      higher prevalence ratios for all complications, and these associations were
      stronger than those observed for the albumin-to-creatinine ratio; after
      multivariable adjustment, however, the associations between eGFR and both
      hypoalbuminemia and hypertension were NS. In conclusion, albuminuria and eGFR
      differentially associate with complications of CKD.

PMID- 21965379
TI  - Long-term consequences of critical illness: a new opportunity for high-impact
      critical care nurses.

PMID- 21965380
TI  - A new view: tele-intensive care unit competencies.
AB  - BACKGROUND Many hospitals have well-planned nursing competency assessment
      programs, but these are meant to measure competency in traditional bedside roles,
      not in tele-intensive care unit (tele-ICU) nurses practicing remotely. OBJECTIVE
      To determine whether current tele-ICU programs have a formal competency
      assessment program and to determine when and how competency of tele-ICU nurses is
      assessed. Method A 20-question survey was provided to a convenience sample of the
      44 known tele-ICU programs nationally. RESULTS Of the surveys distributed, 75%
      were completed and returned. A formal competency assessment policy for assessing
      nurses' competency at the time of hire, during orientation, and ongoing was in
      place at the workplaces of 85% of respondents. The most common methods for
      competency validation were performance appraisal and observation, although peer
      review and self-assessment also were used. Respondents identified the following
      competencies as the highest priorities for defining tele-ICU nurse practice:
      effective listening, prioritization, collaboration, and effective use of tele-ICU
      application tools. CONCLUSION Although awaiting development of professional
      practice standards, many tele-ICU programs currently measure the competence of
      tele-ICU nurses through competency programs.

PMID- 21965381
TI  - Code labs: expediting laboratory test results during a code.
AB  - BACKGROUND Knowing a patient's "laboratory picture" is crucial in any code blue
      situation. Having no streamlined method for collecting and processing laboratory
      specimens during codes leads to staff frustration and critical delays in patient
      care. OBJECTIVE To simplify collection and testing of laboratory specimens during
      codes. METHODS Staff nurses led an initiative through which (1) code laboratory
      tests were placed in a computerized order set, thereby simplifying ordering; (2)
      prepackaged bags of supplies for the new order set were placed in each code cart;
      (3) the laboratory department supervisor began carrying a code pager to ensure
      that laboratory staff are prepared for incoming "code labs"; (4) a protocol was
      created for laboratory staff to follow after receiving code labs; and (5)
      processes were developed for units that are not integrated in the organization's
      electronic ordering system. RESULTS The mean turnaround time (the time from when
      laboratory tests are ordered to when results are posted) was reduced from 52.0
      minutes to 31.3 minutes (P = .002). Laboratory staff improved their processing
      time (the time from when specimens are received by laboratory staff to when
      results are posted) from 34.9 minutes to 21.5 minutes (P = .01). Survey responses
      indicated that staff across disciplines were significantly more satisfied with
      the new process. CONCLUSIONS Because the changes are basic, they can be
      implemented easily in any hospital setting to improve turnaround time for
      laboratory tests during codes.

PMID- 21965382
TI  - Aspiration prevention protocol: decreasing postoperative pneumonia in heart
      surgery patients.
AB  - BACKGROUND Postoperative pneumonia contributes to morbidity and mortality in
      patients who have open heart surgery. OBJECTIVES To determine if measures to
      reduce aspiration in patients after cardiothoracic surgery would decrease the
      occurrence of postoperative pneumonia. METHODS All patients undergoing
      cardiothoracic surgery from April 2008 through October 2008 were prospectively
      enrolled in the study. An aspiration prevention protocol was developed and
      implemented in a 24-bed intensive care unit. The protocol incorporated a bedside
      swallowing evaluation by a speech therapist and progressive oral intake. RESULTS
      In the 6 months before development and implementation of the protocol,
      postoperative pneumonia developed in 11% of patients. After implementation of the
      protocol, no patients had postoperative pneumonia (P < .01). CONCLUSIONS
      Implementing an aspiration prevention protocol was effective in reducing the
      occurrence of postoperative pneumonia in patients who had cardiothoracic surgery.

PMID- 21965383
TI  - The going home initiative: getting critical care patients home with hospice.
AB  - Although considerable effort is being directed at providing patients and their
      families with a "good death," most patients in intensive care units, if given the
      choice, would prefer to die at home. With little guidance from the literature,
      the palliative care committee of an intensive care unit developed guidelines to
      get patients home from the intensive care unit to die. In the past few years, the
      unit has transferred many patients home with hospice care, much to the delight of
      their families. Although several obstacles to achieving this goal exist, the unit
      has achieved success in a small-scale implementation of its Going Home
      Initiative.

PMID- 21965384
TI  - Enhancing leadership orientation through simulation.
AB  - Many novice managers feel unprepared to handle some of the situations that occur
      as a daily part of their job. It is important to provide an environment through
      which novice managers can receive training and develop skills in effective
      communication in complex nursing environments. Simulation-based training can
      provide a safe, interactive way for new managers to develop their communication
      and leadership skills. This type of training allows novice managers to increase
      their confidence and improve their job satisfaction and their management skills.

PMID- 21965385
TI  - Legal aspects of end-of-life care.
AB  - Critical care nurses are essential members of the health care team and often
      assist patients and patients' families who are facing end-of-life concerns. In
      that role, a nurse needs an understanding of many important factors, including
      legal implications associated with the end of life. Since the 1970s, courts have
      decided several cases that have established legal principles in end-of-life care.
      Courts have found that competent adults have the right to refuse or discontinue
      medical interventions. For incompetent adults and children, decisions are made by
      a surrogate. In the absence of an advance directive or documentation of goals of
      care, the surrogate, in collaboration with the medical team, determines a plan of
      care, including decisions about end-of-life care. When issues of medical futility
      occur, attempts to work with patients and their families should be undertaken,
      but if the dispute cannot be resolved, a transfer in care may be the only option.

PMID- 21965386
TI  - Ambulating with pulmonary artery or femoral catheters in place.

PMID- 21965387
TI  - Skin Care Oktoberfest: a creative approach to pressure ulcer prevention education
      in a pediatric intensive care unit.

PMID- 21965388
TI  - I am a critical care nurse.

PMID- 21965389
TI  - Essential nursing competencies for genetics and genomics: implications for
      critical care.
AB  - The implications of genetics and genomics for critical care nurses are becoming
      more evident, not only in the care provided but also in the numerous medications
      administered. Genetic causes are being discovered for an increasing number of
      chronic illnesses and diseases, such as Huntington disease. Because of the
      scientific and pharmacological advances, leading nursing organizations, such as
      the American Nurses Association, have established competencies in genetic
      knowledge for nurses. Such competencies help ensure quality care. Recent advances
      in the pharmacogenomics of therapy for human immunodeficiency virus disease,
      cancer, cardiovascular disease, and malignant hyperthermia have indicated a
      genetic linkage; therefore treatments are targeted toward the genetic aspect of
      the abnormality. Critical care nurses need knowledge of these genetic conditions
      and of medications affected by genetic factors.

PMID- 21965390
TI  - Critically ill patients with H1N1 influenza A undergoing extracorporeal membrane
      oxygenation.
AB  - The most common cause of death due to the H1N1 subtype of influenza A virus
      (swine flu) in the 2009 to 2010 epidemic was severe acute respiratory failure
      that persisted despite advanced mechanical ventilation strategies. Extracorporeal
      membrane oxygenation (ECMO) was used as a salvage therapy for patients refractory
      to traditional treatment. At Legacy Emanuel Hospital, Portland, Oregon, the
      epidemic resulted in a critical care staffing crisis. Among the 15 patients with
      H1N1 influenza A treated with ECMO, 4 patients received the therapy
      simultaneously. The role of ECMO in supporting patients with severe respiratory
      failure due to H1N1 influenza is described, followed by discussions of the
      nursing care challenges for each body system. Variations from standards of care,
      operational considerations regarding staff workload, institutional burden, and
      emotional wear and tear of the therapy on patients, patients' family members, and
      the entire health care team are also addressed. Areas for improvement for
      providing care of the critically ill patient requiring ECMO are highlighted in
      the conclusion.

PMID- 21965391
TI  - Differential degradation of bicyclics with aromatic and alicyclic rings by
      Rhodococcus sp. strain DK17.
AB  - The metabolically versatile Rhodococcus sp. strain DK17 is able to grow on
      tetralin and indan but cannot use their respective desaturated counterparts, 1,2
      dihydronaphthalene and indene, as sole carbon and energy sources. Metabolite
      analyses by gas chromatography-mass spectrometry and nuclear magnetic resonance
      spectrometry clearly show that (i) the meta-cleavage dioxygenase mutant strain
      DK180 accumulates 5,6,7,8-tetrahydro-1,2-naphthalene diol, 1,2-indene diol, and
      3,4-dihydro-naphthalene-1,2-diol from tetralin, indene, and 1,2
      dihydronaphthalene, respectively, and (ii) when expressed in Escherichia coli,
      the DK17 o-xylene dioxygenase transforms tetralin, indene, and 1,2
      dihydronaphthalene into tetralin cis-dihydrodiol, indan-1,2-diol, and cis-1,2
      dihydroxy-1,2,3,4-tetrahydronaphthalene, respectively. Tetralin, which is
      activated by aromatic hydroxylation, is degraded successfully via the ring
      cleavage pathway to support growth of DK17. Indene and 1,2-dihydronaphthalene do
      not serve as growth substrates because DK17 hydroxylates them on the alicyclic
      ring and further metabolism results in a dead-end metabolite. This study reveals
      that aromatic hydroxylation is a prerequisite for proper degradation of bicyclics
      with aromatic and alicyclic rings by DK17 and confirms the unique ability of the
      DK17 o-xylene dioxygenase to perform distinct regioselective hydroxylations.

PMID- 21965392
TI  - Mutations suppressing the loss of DegQ function in Bacillus subtilis (natto) poly
      gamma-glutamate synthesis.
AB  - The degQ gene of Bacillus subtilis (natto), encoding a small peptide of 46 amino
      acids, is essential for the synthesis of extracellular poly-gamma-glutamate
      (gammaPGA). To elucidate the role of DegQ in gammaPGA synthesis, we knocked out
      the degQ gene in Bacillus subtilis (natto) and screened for suppressor mutations
      that restored gammaPGA synthesis in the absence of DegQ. Suppressor mutations
      were found in degS, the receptor kinase gene of the DegS-DegU two-component
      system. Recombinant DegS-His(6) mutant proteins were expressed in Escherichia
      coli cells and subjected to an in vitro phosphorylation assay. Compared with the
      wild type, mutant DegS-His(6) proteins showed higher levels of
      autophosphorylation (R208Q, M195I, L248F, and D250N), reduced
      autodephosphorylation (D250N), reduced phosphatase activity toward DegU, or a
      reduced ability to stimulate the autodephosphorylation activity of DegU (R208Q,
      D249G, M195I, L248F, and D250N) and stabilized DegU in the phosphorylated form.
      These mutant DegS proteins mimic the effect of DegQ on wild-type DegSU in vitro.
      Interestingly, DegQ stabilizes phosphorylated DegS only in the presence of DegU,
      indicating a complex interaction of these three proteins.

PMID- 21965393
TI  - Cotransmission of divergent relapsing fever spirochetes by artificially infected
      Ornithodoros hermsi.
AB  - The soft tick Ornithodoros hermsi, which ranges in specific arboreal zones of
      western North America, acts as a vector for the relapsing fever spirochete
      Borrelia hermsii. Two genomic groups (genomic group I [GGI] and GGII) of B.
      hermsii are differentiated by multilocus sequence typing yet are codistributed in
      much of the vector's range. To test whether the tick vector can be infected via
      immersion, noninfected, colony-derived O. hermsi larvae were exposed to reduced
      humidity conditions before immersion in culture suspensions of several GGI and
      GGII isolates. We tested for spirochetes in ticks by immunofluorescence
      microscopy and in mouse blood by quantitative PCR of the vtp locus to
      differentiate spirochete genotypes. The immersed larval ticks were capable of
      spirochete transmission to mice at the first nymphal feeding. Tick infection with
      mixed cultures of isolates DAH (vtp-6) (GGI) and MTW-2 (vtp-5) (GGII) resulted in
      ticks that caused spirochetemias in mice consisting of MTW-2 or both DAH and MTW
      2. These findings show that this soft tick species can acquire B. hermsii by
      immersion in spirochete suspensions, that GGI and GGII isolates can coinfect the
      tick vector by this method, and that these spirochetes can be cotransmitted to a
      rodent host.

PMID- 21965394
TI  - Mother-to-child transmission of and multiple-strain colonization by Bacteroides
      fragilis in a cohort of mothers and their children.
AB  - Bacteroides fragilis represents an early infant colonizer with important host
      interactions. Our knowledge about the diversity, transmission, and persistence of
      this bacterium, however, is limited. Here, we addressed these questions using a
      combination of multilocus sequence typing (MLST) and variable-number tandem
      repeat (VNTR) sequence analyses. We used both culture-dependent and -independent
      typing. We genotyped B. fragilis in fecal samples from a cohort of 93 mothers and
      their children, with samples taken from the mothers and from the children at the
      ages 1 to 10 days, 4 months, 1 year, and 2 years. By MLST we found two main B.
      fragilis groups, which we denoted clades A and B. Direct typing of stool samples
      using the icd gene revealed seven sequence types, five within clade A and two
      within clade B. A single clade A sequence type, however, represented 79% of all
      the sequences. This sequence type was further subtyped using VNTR. VNTR subtyping
      revealed 16 different VNTR types. Based on the distribution patterns of these, we
      show mother-to-child transmission and multiple-strain colonization. We argue that
      negative host selection promotes the coexistence of multiple strains. The
      significance of our findings is that we have started unraveling the transmission
      and persistence patterns of one of the most important human gut colonizers.

PMID- 21965395
TI  - Field-scale transplantation experiment to investigate structures of soil
      bacterial communities at pioneering sites.
AB  - Studies on the effect of environmental conditions on plants and microorganisms
      are a central issue in ecology, and they require an adequate experimental setup.
      A strategy often applied in geobotanical studies is based on the reciprocal
      transplantation of plant species at different sites. We adopted a similar
      approach as a field-based tool to investigate the relationships of soil bacterial
      communities with the environment. Soil samples from two different (calcareous and
      siliceous) unvegetated glacier forefields were reciprocally transplanted and
      incubated for 15 months between 2009 and 2010. Controls containing local soils
      were included. The sites were characterized over time in terms of geographical
      (bedrock, exposition, sunlight, temperature, and precipitation) and
      physicochemical (texture, water content, soluble and nutrients) features. The
      incubating local ("home") and transplanted ("away") soils were monitored for
      changes in extractable nutrients and in the bacterial community structure,
      defined through terminal restriction fragment length polymorphism (T-RFLP) of the
      16S rRNA gene. Concentrations of soluble ions in most samples were more
      significantly affected by seasons than by the transplantation. For example,
      NO(3)(-) showed a seasonal pattern, increasing from 1 to 3 MUg NO(3)(-) (g soil
      dry weight)(-1) after the melting of snow but decreasing to <1 MUg NO(3)(-) (g
      soil dry weight)(-1) in autumn. Seasons, and in particular strong precipitation
      events occurring in the summer of 2010 (200 to 300 mm of rain monthly), were also
      related to changes of bacterial community structures. Our results show the
      suitability of this approach to compare responses of bacterial communities to
      different environmental conditions directly in the field.

PMID- 21965396
TI  - Combined effect of improved cell yield and increased specific productivity
      enhances recombinant enzyme production in genome-reduced Bacillus subtilis strain
      MGB874.
AB  - Genome reduction strategies to create genetically improved cellular biosynthesis
      machineries for proteins and other products have been pursued by use of a wide
      range of bacteria. We reported previously that the novel Bacillus subtilis strain
      MGB874, which was derived from strain 168 and has a total genomic deletion of 874
      kb (20.7%), exhibits enhanced production of recombinant enzymes. However, it was
      not clear how the genomic reduction resulted in elevated enzyme production. Here
      we report that deletion of the rocDEF-rocR region, which is involved in arginine
      degradation, contributes to enhanced enzyme production in strain MGB874. Deletion
      of the rocDEF-rocR region caused drastic changes in glutamate metabolism, leading
      to improved cell yields with maintenance of enzyme productivity. Notably, the
      specific enzyme productivity was higher in the reduced-genome strain, with or
      without the rocDEF-rocR region, than in wild-type strain 168. The high specific
      productivity in strain MGB874 is likely attributable to the higher expression
      levels of the target gene resulting from an increased promoter activity and
      plasmid copy number. Thus, the combined effects of the improved cell yield by
      deletion of the rocDEF-rocR region and the increased specific productivity by
      deletion of another gene(s) or the genomic reduction itself enhanced the
      production of recombinant enzymes in MGB874. Our findings represent a good
      starting point for the further improvement of B. subtilis reduced-genome strains
      as cell factories for the production of heterologous enzymes.

PMID- 21965397
TI  - Significance of microbial communities and interactions in safeguarding reactive
      mine tailings by ecological engineering.
AB  - Pyritic mine tailings (mineral waste generated by metal mining) pose significant
      risk to the environment as point sources of acidic, metal-rich effluents (acid
      mine drainage [AMD]). While the accelerated oxidative dissolution of pyrite and
      other sulfide minerals in tailings by acidophilic chemolithotrophic prokaryotes
      has been widely reported, other acidophiles (heterotrophic bacteria that catalyze
      the dissimilatory reduction of iron and sulfur) can reverse the reactions
      involved in AMD genesis, and these have been implicated in the "natural
      attenuation" of mine waters. We have investigated whether by manipulating
      microbial communities in tailings (inoculating with iron- and sulfur-reducing
      acidophilic bacteria and phototrophic acidophilic microalgae) it is possible to
      mitigate the impact of the acid-generating and metal-mobilizing chemolithotrophic
      prokaryotes that are indigenous to tailing deposits. Sixty tailings mesocosms
      were set up, using five different microbial inoculation variants, and analyzed at
      regular intervals for changes in physicochemical and microbiological parameters
      for up to 1 year. Differences between treatment protocols were most apparent
      between tailings that had been inoculated with acidophilic algae in addition to
      aerobic and anaerobic heterotrophic bacteria and those that had been inoculated
      with only pyrite-oxidizing chemolithotrophs; these differences included higher pH
      values, lower redox potentials, and smaller concentrations of soluble copper and
      zinc. The results suggest that empirical ecological engineering of tailing
      lagoons to promote the growth and activities of iron- and sulfate-reducing
      bacteria could minimize their risk of AMD production and that the heterotrophic
      populations could be sustained by facilitating the growth of microalgae to
      provide continuous inputs of organic carbon.

PMID- 21965399
TI  - Hemolytic porcine intestinal Escherichia coli without virulence-associated genes
      typical of intestinal pathogenic E. coli.
AB  - Testing 1,666 fecal or intestinal samples from healthy and diarrheic pigs, we
      obtained hemolytic Escherichia coli isolates from 593 samples. Focusing on
      hemolytic E. coli isolates without virulence-associated genes (VAGs) typical for
      enteropathogens, we found that such isolates carried a broad variety of VAGs
      typical for extraintestinal pathogenic E. coli.

PMID- 21965398
TI  - Bacterial communities of two parthenogenetic aphid species cocolonizing two host
      plants across the Hawaiian Islands.
AB  - Aphids (Hemiptera: Aphididae) have been the focus of several studies with respect
      to their interactions with inherited symbionts, but bacterial communities of most
      aphid species are still poorly characterized. In this research, we used bar-coded
      pyrosequencing to characterize bacterial communities in aphids. Specifically, we
      examined the diversity of bacteria in two obligately parthenogenetic aphid
      species (the melon aphid, Aphis gossypii, and the cardamom aphid, Pentalonia
      caladii) cocolonizing two plant species (taro, Colocasia esculenta, and ginger,
      Alpinia purpurata) across four Hawaiian Islands (Hawaii, Kauai, Maui, and Oahu).
      Results from this study revealed that heritable symbionts dominated the bacterial
      communities for both aphid species. The bacterial communities differed
      significantly between the two species, and A. gossypii harbored a more diverse
      bacterial community than P. caladii. The bacterial communities also differed
      across aphid populations sampled from the different islands; however, communities
      did not differ between aphids collected from the two host plants.

PMID- 21965400
TI  - DNA detection and genotypic identification of potentially human-pathogenic
      microsporidia from asymptomatic pet parrots in South Korea as a risk factor for
      zoonotic emergence.
AB  - We detected and identified genotypes of human-pathogenic microsporidia in fecal
      samples from 51 asymptomatic captive-bred pet parrots in South Korea.
      Microsporidia were identified in 8 samples (15.7%); 7 parrots tested positive for
      Encephalitozoon hellem, and 1 parrot tested positive for both E. hellem and
      Encephalitozoon cuniculi. In genotypic identifications, E. hellem was present in
      genotypes 1A and 2B and E. cuniculi was present in genotype II. Pet parrots might
      be a source of human microsporidian infection.

PMID- 21965401
TI  - Induction of viable but nonculturable Escherichia coli O157:H7 in the
      phyllosphere of lettuce: a food safety risk factor.
AB  - Escherichia coli O157:H7 continues to be an important human pathogen and has been
      increasingly linked to food-borne illness associated with fresh produce,
      particularly leafy greens. The aim of this work was to investigate the fate of E.
      coli O157:H7 on the phyllosphere of lettuce under low temperature and to evaluate
      the potential hazard of viable but nonculturable (VBNC) cells induced under such
      stressful conditions. First, we studied the survival of six bacterial strains
      following prolonged storage in water at low temperature (4 degrees C) and
      selected two strains with different nonculturable responses for the construction
      of E. coli O157:H7 Tn7gfp transformants in order to quantitatively assess the
      occurrence of human pathogens on the plant surface. Under a suboptimal growth
      temperature (16 degrees C), both E. coli O157:H7 strains maintained culturability
      on lettuce leaves, but under more stressful conditions (8 degrees C), the
      bacterial populations evolved toward the VBNC state. The strain-dependent
      nonculturable response was more evident in the experiments with different
      inoculum doses (10(9) and 10(6) E. coli O157:H7 bacteria per g of leaf) when
      strain BRMSID 188 lost culturability after 15 days and strain ATCC 43895 lost
      culturability within 7 days, regardless of the inoculum dose. However, the number
      of cells entering the VBNC state in high-cell-density inoculum (approximately
      55%) was lower than in low-cell-density inoculum (approximately 70%). We recorded
      the presence of verotoxin for 3 days in samples that contained a VBNC population
      of 4 to 5 log(10) cells but did not detect culturable cells. These findings
      indicate that E. coli O157:H7 VBNC cells are induced on lettuce plants, and this
      may have implications regarding food safety.

PMID- 21965402
TI  - Subtilase cytotoxin-coding genes in verotoxin-producing Escherichia coli strains
      from sheep and goats differ from those from cattle.
AB  - Subtilase cytotoxin (SubAB) from verotoxin (VT)-producing Escherichia coli (VTEC)
      strains was first described in the 98NK2 strain and has been associated with
      human disease. However, SubAB has recently been found in two VT-negative E. coli
      strains (ED 591 and ED 32). SubAB is encoded by two closely linked, cotranscribed
      genes (subA and subB). In this study, we investigated the presence of subAB genes
      in 52 VTEC strains isolated from cattle and 209 strains from small ruminants,
      using PCR. Most (91.9%) VTEC strains from sheep and goats and 25% of the strains
      from healthy cattle possessed subAB genes. The presence of subAB in a high
      percentage of the VTEC strains from small ruminants might increase the
      pathogenicity of these strains for human beings. Some differences in the results
      of PCRs and in the association with some virulence genes suggested the existence
      of different variants of subAB. We therefore sequenced the subA gene in 12
      strains and showed that the subA gene in most of the subAB-positive VTEC strains
      from cattle was almost identical (about 99%) to that in the 98NK2 strain, while
      the subA gene in most of the subAB-positive VTEC strains from small ruminants was
      almost identical to that in the ED 591 strain. We propose the terms subAB1 to
      describe the SubAB-coding genes resembling that in the 98NK2 strain and subAB2 to
      describe those resembling that in the ED 591 strain.

PMID- 21965403
TI  - National validation study of a cellulose sponge wipe-processing method for use
      after sampling Bacillus anthracis spores from surfaces.
AB  - This work was initiated to address the gaps identified by Congress regarding
      validated biothreat environmental sampling and processing methods. Nine
      Laboratory Response Network-affiliated laboratories participated in a validation
      study of a cellulose sponge wipe-processing protocol for the recovery, detection,
      and quantification of viable Bacillus anthracis Sterne spores from steel
      surfaces. Steel coupons (645.16 cm(2)) were inoculated with 1 to 4 log(10) spores
      and then sampled with cellulose sponges (Sponge-Stick; 3M, St. Paul, MN).
      Surrogate dust and background organisms were added to the sponges to mimic
      environmental conditions. Labs processed the sponges according to the provided
      protocol. Sensitivity, specificity, and mean percent recovery (%R), between-lab
      variability, within-lab variability, and total percent coefficient of variation
      were calculated. The mean %R (standard error) of spores from the surface was 32.4
      (4.4), 24.4 (2.8), and 30.1 (2.3) for the 1-, 2-, and 4-log(10) inoculum levels,
      respectively. Sensitivities for colony counts were 84.1%, 100%, and 100% for the
      1-, 2-, and 4-log(10) inocula, respectively. These data help to characterize the
      variability of the processing method and thereby enhance confidence in the
      interpretation of the results of environmental sampling conducted during a B.
      anthracis contamination investigation.

PMID- 21965404
TI  - Survival and heat resistance of Salmonella enterica and Escherichia coli O157:H7
      in peanut butter.
AB  - Significant differences (P < 0.05) were found between the survival rates of
      Salmonella enterica and Escherichia coli O157:H7 in peanut butter with different
      formulations and water activity. High carbohydrate content in peanut butter and
      low incubation temperature resulted in higher levels of bacterial survival during
      storage but lower levels of bacterial resistance to heat treatment.

PMID- 21965405
TI  - Competitive selection of lactic acid bacteria that persist in the human oral
      cavity.
AB  - Lactic acid bacteria (LAB) might offer opportunities as oral probiotics provided
      candidate strains persist in the mouth. After intake of a mixture of 69 LAB,
      strains of Lactobacillus fermentum and Lactobacillus salivarius were especially
      recovered. Coaggregation with other microbes is likely not a prerequisite for
      persistence since L. salivarius strongly coaggregated with typical oral cavity
      isolates, whereas L. fermentum failed to display this phenotype.

PMID- 21965406
TI  - Endo-beta-1,3-glucanase GLU1, from the fruiting body of Lentinula edodes, belongs
      to a new glycoside hydrolase family.
AB  - The cell wall of the fruiting body of the mushroom Lentinula edodes is degraded
      after harvesting by enzymes such as beta-1,3-glucanase. In this study, a novel
      endo-type beta-1,3-glucanase, GLU1, was purified from L. edodes fruiting bodies
      after harvesting. The gene encoding it, glu1, was isolated by rapid amplification
      of cDNA ends (RACE)-PCR using primers designed from the N-terminal amino acid
      sequence of GLU1. The putative amino acid sequence of the mature protein
      contained 247 amino acid residues with a molecular mass of 26 kDa and a pI of
      3.87, and recombinant GLU1 expressed in Pichia pastoris exhibited beta-1,3
      glucanase activity. GLU1 catalyzed depolymerization of glucans composed of beta
      1,3-linked main chains, and reaction product analysis by thin-layer
      chromatography (TLC) clearly indicated that the enzyme had an endolytic mode.
      However, the amino acid sequence of GLU1 showed no significant similarity to
      known glycoside hydrolases. GLU1 has similarity to several hypothetical proteins
      in fungi, and GLU1 and highly similar proteins should be classified as a novel
      glycoside hydrolase family (GH128).

PMID- 21965407
TI  - Development and characterization of a xylose-inducible gene expression system for
      Clostridium perfringens.
AB  - A xylose-inducible gene expression vector for Clostridium perfringens was
      developed. Plasmid pXCH contains a chromosomal region from Clostridium difficile
      (xylR-P(xy)(lB)): xylR, encoding the xylose repressor, xylO, the xyl operator
      sequence, and P(xylB), the divergent promoter upstream of xylBA encoding xylulo
      kinase and xylose isomerase. pXCH allows tightly regulated expression of the
      chloramphenicol acetyltransferase reporter and the alpha-toxin genes in response
      to the inducer concentration. Thus, pXCH could constitute a new valuable genetic
      tool for study of C. perfringens.

PMID- 21965408
TI  - High ethanol titers from cellulose by using metabolically engineered
      thermophilic, anaerobic microbes.
AB  - This work describes novel genetic tools for use in Clostridium thermocellum that
      allow creation of unmarked mutations while using a replicating plasmid. The
      strategy employed counter-selections developed from the native C. thermocellum
      hpt gene and the Thermoanaerobacterium saccharolyticum tdk gene and was used to
      delete the genes for both lactate dehydrogenase (Ldh) and phosphotransacetylase
      (Pta). The Deltaldh Deltapta mutant was evolved for 2,000 h, resulting in a
      stable strain with 40:1 ethanol selectivity and a 4.2-fold increase in ethanol
      yield over the wild-type strain. Ethanol production from cellulose was
      investigated with an engineered coculture of organic acid-deficient engineered
      strains of both C. thermocellum and T. saccharolyticum. Fermentation of 92
      g/liter Avicel by this coculture resulted in 38 g/liter ethanol, with acetic and
      lactic acids below detection limits, in 146 h. These results demonstrate that
      ethanol production by thermophilic, cellulolytic microbes is amenable to
      substantial improvement by metabolic engineering.

PMID- 21965409
TI  - Genome and proteome of Campylobacter jejuni bacteriophage NCTC 12673.
AB  - Campylobacter jejuni continues to be the leading cause of bacterial food-borne
      illness worldwide, so improvements to current methods used for bacterial
      detection and disease prevention are needed. We describe here the genome and
      proteome of C. jejuni bacteriophage NCTC 12673 and the exploitation of its
      receptor-binding protein for specific bacterial detection. Remarkably, the 135-kb
      Myoviridae genome of NCTC 12673 differs greatly from any other proteobacterial
      phage genome described (including C. jejuni phages CP220 and CPt10) and instead
      shows closest homology to the cyanobacterial T4-related myophages. The phage
      genome contains 172 putative open reading frames, including 12 homing
      endonucleases, no visible means of packaging, and a putative trans-splicing
      intein. The phage DNA appears to be strongly associated with a protein that
      interfered with PCR amplification and estimation of the phage genome mass by
      pulsed-field gel electrophoresis. Identification and analyses of the receptor
      binding protein (Gp48) revealed features common to the Salmonella enterica P22
      phage tailspike protein, including the ability to specifically recognize a host
      organism. Bacteriophage receptor-binding proteins may offer promising
      alternatives for use in pathogen detection platforms.

PMID- 21965410
TI  - Pyruvate and lactate metabolism by Shewanella oneidensis MR-1 under fermentation,
      oxygen limitation, and fumarate respiration conditions.
AB  - Shewanella oneidensis MR-1 is a facultative anaerobe that derives energy by
      coupling organic matter oxidation to the reduction of a wide range of electron
      acceptors. Here, we quantitatively assessed the lactate and pyruvate metabolism
      of MR-1 under three distinct conditions: electron acceptor-limited growth on
      lactate with O(2), lactate with fumarate, and pyruvate fermentation. The latter
      does not support growth but provides energy for cell survival. Using
      physiological and genetic approaches combined with flux balance analysis, we
      showed that the proportion of ATP produced by substrate-level phosphorylation
      varied from 33% to 72.5% of that needed for growth depending on the electron
      acceptor nature and availability. While being indispensable for growth, the
      respiration of fumarate does not contribute significantly to ATP generation and
      likely serves to remove formate, a product of pyruvate formate-lyase-catalyzed
      pyruvate disproportionation. Under both tested respiratory conditions, S.
      oneidensis MR-1 carried out incomplete substrate oxidation, whereby the
      tricarboxylic acid (TCA) cycle did not contribute significantly. Pyruvate
      dehydrogenase was not involved in lactate metabolism under conditions of O(2)
      limitation but was required for anaerobic growth, likely by supplying reducing
      equivalents for biosynthesis. The results suggest that pyruvate fermentation by
      S. oneidensis MR-1 cells represents a combination of substrate-level
      phosphorylation and respiration, where pyruvate serves as an electron donor and
      an electron acceptor. Pyruvate reduction to lactate at the expense of formate
      oxidation is catalyzed by a recently described new type of oxidative NAD(P)H
      independent d-lactate dehydrogenase (Dld-II). The results further indicate that
      pyruvate reduction coupled to formate oxidation may be accompanied by the
      generation of proton motive force.

PMID- 21965411
TI  - Use of a DNA microarray for detection and identification of bacterial pathogens
      associated with fishery products.
AB  - We established a microarray for the simultaneous detection and identification of
      diverse putative pathogens often associated with fishery products by targeting
      specific genes of Listeria monocytogenes, Salmonella, Shigella, Staphylococcus
      aureus, Streptococcus pyogenes, Vibrio cholerae, Vibrio parahaemolyticus, Vibrio
      vulnificus, and Yersinia enterocolitica and the 16S-23S rRNA gene internal
      transcribed spacer (ITS) region of Proteus mirabilis and Proteus vulgaris. The
      microarray contained 26 specific probes and was tested against a total of 123
      target bacterial strains that included 55 representative strains, 68 clinical
      isolates, and 45 strains of other bacterial species that belonged to 8 genera and
      34 species, and it was shown to be specific and reproducible. A detection
      sensitivity of 10 ng DNA or 10 CFU/ml for pure cultures of each target organism
      demonstrated that the assay was highly sensitive and reproducible. Mock and real
      fishery product samples were tested by the microarray, and the accuracy was 100%.
      The DNA microarray method described in this communication is specific, sensitive,
      and reliable and has several advantages over traditional methods of bacterial
      culture and antiserum agglutination assays.

PMID- 21965412
TI  - Characterization and quantitation of a novel beta-lactamase gene found in a
      wastewater treatment facility and the surrounding coastal ecosystem.
AB  - Wastewater treatment plants (WWTPs) are engineered structures that collect,
      concentrate, and treat human waste, ultimately releasing treated wastewater into
      local environments. While WWTPs efficiently remove most biosolids, it has been
      shown that many antibiotics and antibiotic-resistant bacteria can survive the
      treatment process. To determine how WWTPs influence the concentration and
      dissemination of antibiotic-resistant genes into the environment, a functional
      metagenomic approach was used to identify a novel antibiotic resistance gene
      within a WWTP, and quantitative PCR (qPCR) was used to determine gene copy
      numbers within the facility and the local coastal ecosystem. From the WWTP
      metagenomic library, the fosmid insert contained in one highly resistant clone
      (MIC, ~ 416 MUg ml(-1) ampicillin) was sequenced and annotated, revealing 33
      putative genes, including a 927-bp gene that is 42% identical to a functionally
      characterized beta-lactamase from Staphylococcus aureus PC1. Isolation and
      subcloning of this gene, referred to as bla(M-1), conferred ampicillin resistance
      to its Escherichia coli host. When normalized to volume, qPCR showed increased
      concentrations of bla(M-1) during initial treatment stages but 2-fold-decreased
      concentrations during the final treatment stage. The concentration ng(-1) DNA
      increased throughout the WWTP process from influent to effluent, suggesting that
      bla(M-1) makes up a significant proportion of the overall genetic material being
      released into the coastal ecosystem. Average discharge was estimated to be 3.9 *
      10(14) copies of the bla(M-1) gene released daily into this coastal ecosystem.
      Furthermore, the gene was observed in all sampled coastal water and sediment
      samples surrounding the facility. Our results suggest that WWTPs may be a pathway
      for the dissemination of novel antibiotic resistance genes into the environment.

PMID- 21965413
TI  - Identification of fecal input sites in spring water by selection and genotyping
      of multiresistant Escherichia coli.
AB  - The localization of fecal input sites is important for water quality management.
      For this purpose, we have developed a new approach based on a three-step
      procedure, including a preparatory phase, the screening of multiresistant
      bacteria using selective agar plates, and a typing phase where selected
      Escherichia coli isolates are characterized by antibiotic resistance profiles and
      molecular fingerprinting techniques (pulsed-field gel electrophoresis [PFGE]).
      These two well-known source tracking methods were combined in order to reduce
      cost and effort. This approach was successfully applied under field conditions in
      a study area located in the north-western part of Switzerland. E. coli isolates
      from spring water and surface water samples collected in this area were screened
      with selective agar plates. In this way, 21 different groups, each consisting of
      strains with the same pattern of antibiotic resistance, were found. Of these,
      four groups were further analyzed using PFGE. Strains with identical PFGE
      profiles were detected repeatedly, demonstrating the suitability of this method
      for the localization of fecal input sites over an extended period of time.
      Identical PFGE patterns of strains detected in water from two different springs
      were also found in the stream flowing through the study area. These results
      demonstrated the applicability of the new approach for the examination of
      incidents of fecal contamination in drinking water. The advantages of the
      described approach over genotyping methods currently being used to identify
      sources of fecal contaminants are a reduction in time, costs, and the effort
      required. Identical isolates could be identified without the construction of
      large libraries.

PMID- 21965414
TI  - Slower gait, slower information processing and smaller prefrontal area in older
      adults.
AB  - BACKGROUND: Slower gait in older adults is related to smaller volume of the
      prefrontal area (PFAv). The pathways underlying this association have not yet
      been explored. Understanding slowing gait could help improve function in older
      age. We examine whether the association between smaller PFAv and slower gait is
      explained by lower performance on numerous neuropsychological tests. HYPOTHESIS:
      We hypothesise that slower information processing explains this association,
      while tests of language or memory will not. METHODS: Data on brain imaging,
      neuropsychological tests (information processing speed, visuospatial attention,
      memory, language, mood) and time to walk 15 feet were obtained in 214 adults
      (73.3 years, 62% women) free from stroke and dementia. Covariates included
      central (white matter hyperintensities, vision) and peripheral contributors of
      gait (vibration sense, muscle strength, arthritis, body mass index), demographics
      (age, race, gender, education), as well as markers of prevalent vascular diseases
      (cardiovascular disease, diabetes and ankle arm index). RESULTS: In linear
      regression models, smaller PFAv was associated with slower time to walk
      independent of covariates. This association was no longer significant after
      adding information processing speed to the model. None of the other
      neuropsychological tests significantly attenuated this association. CONCLUSIONS:
      We conclude that smaller PFAv may contribute to slower gait through slower
      information processing. Future longitudinal studies are warranted to examine the
      casual relationship between focal brain atrophy with slowing in information
      processing and gait.

PMID- 21965415
TI  - Molecular evidence of transient therapeutic effectiveness of natalizumab despite
      high-titre neutralizing antibodies.
AB  - Natalizumab is a humanized monoclonal antibody directed against the alpha-4
      integrin subunit of very late activation antigen-4 (VLA-4). Natalizumab
      neutralizing antibodies (NAB) have been found to significantly reduce beneficial
      effects of natalizumab treatment in multiple sclerosis. We investigated
      interactions of NAB with natalizumab by serial measurements of alpha-4 integrin
      levels on peripheral blood mononuclear cells using flow cytometry. In addition,
      serum concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1), the
      endothelial ligand of VLA-4, and serum NAB were serially determined. Natalizumab
      infusion led to a transient reduction in alpha-4 integrin levels on immune cells
      and serum sVCAM-1 levels along with serum negativity of NAB lasting for a few
      days post-infusion. Apparently, the high-dose effect of freshly infused
      natalizumab resulted in a transient neutralization of NAB possibly involving a
      transient therapeutic effectiveness.

PMID- 21965416
TI  - Cytokine mapping in cerebrospinal fluid and blood in multiple sclerosis patients
      without oligoclonal bands.
AB  - OBJECTIVE: Since there are clinical and genetic differences between MS patients
      with intrathecal oligoclonal bands (OCB+) in the cerebrospinal fluid (CSF)
      compared with those without (OCB-), the aim was to find out if OCB- patients
      showed a different pattern of cytokine immune activation compared with OCB+
      patients. METHODS: The study included 25 MS patients (10 OCB- and 15 OCB+) and 13
      controls. A panel of cytokines was measured; IL-1beta, IL-6, IL-8/CXCL8, IL-10,
      TNF and GM-CSF in serum, CSF and in supernatants from polyclonally stimulated
      blood mononuclear cells, where also levels of IL-12p40, IL-13, IL-15, IL-17 and
      IFN-gamma were measured. The concentrations of soluble (s) VCAM-1 and sCD14 were
      measured in serum and CSF. RESULTS: In general, there were no extensive
      differences in cytokine concentrations between the OCB- and OCB+ groups.
      CONCLUSION: OCB- MS patients do not seem to constitute a separate entity
      concerning inflammatory parameters measured as cytokine concentrations in CSF and
      blood.

PMID- 21965417
TI  - Examining sleep, fatigue, and daytime sleepiness in pediatric multiple sclerosis
      patients.
AB  - BACKGROUND: About 2-5% of patients with multiple sclerosis (MS) experience their
      first symptoms before age 18. Sleep disorders occur frequently in MS. The
      prevalence of sleep problems and their impact on fatigue and daytime sleepiness
      in pediatric MS is unknown. OBJECTIVE: To determine whether pediatric MS patients
      have more sleep disturbances, fatigue, and daytime sleepiness compared with an
      age-, sex-, and race-matched control group. METHODS: Patients and age-, sex-, and
      race-matched controls were surveyed to quantify daytime sleepiness via the
      modified Epworth Sleepiness Scale, sleep quality and hygiene through the
      Adolescent Sleep Wake and Hygiene Scale, respectively, and fatigue using the
      PediatricQL Multidimensional Fatigue Scale. RESULTS: Pediatric MS patients (n =
      30) and age-, sex-, and race-matched controls (n = 52) had similar levels of
      fatigue; however, when compared with previously published historical controls,
      both groups reported worse fatigue across all dimensions (p < 0.05). Pediatric MS
      patients also had similar sleep quality compared with the matched controls, but
      reported better sleep hygiene on the 'sleep stability' dimension (p < 0.05). In
      addition, pediatric MS patients had less daytime sleepiness than the matched
      controls (p < 0.05). CONCLUSION: Although patients with MS reported similar
      levels of fatigue, they have better sleep hygiene, which could possibly account
      for the decreased amount of excessive daytime sleepiness. Also, when compared
      with historical controls, the MS and control samples reported more fatigue. Thus,
      caution must be taken when using published control data, especially when not
      properly matched.

PMID- 21965418
TI  - Quantitative measurement of anti-aquaporin-4 antibodies by enzyme-linked
      immunosorbent assay using purified recombinant human aquaporin-4.
AB  - BACKGROUND: Antibodies to aquaporin-4 (AQP4-Ab), known as NMO-IgG, are a
      sensitive and specific marker for neuromyelitis optica (NMO). METHODS: To develop
      an enzyme-linked immunosorbent assay (ELISA) for AQP4-Ab, we expressed M23
      isoform of human AQP4 in a baculovirus system, and used it as an antigen. We
      measured AQP4-Ab in the sera of 300 individuals: 64 with definite NMO, 31 with
      high-risk NMO, 105 with multiple sclerosis (MS), 57 with other neurological
      diseases (ONDs), and 43 healthy controls. We also performed longitudinal
      measurements of AQP4-Ab in 787 samples collected from 51 patients with definite
      or high-risk NMO. RESULTS: AQP4-Abs were positive in 72% with definite NMO, 55%
      with high-risk NMO, and 4% with MS, but none of the OND patients and the healthy
      individuals. The longitudinal measurement showed AQP4-Ab levels correlating with
      disease activity. Out of 38 initially seropositive patients, 21 became
      seronegative under effective immunosuppressive therapy. During most relapses, the
      serum AQP4-Ab levels were either high or rising compared with the previous value,
      although rising AQP4-Ab levels did not always lead to acute exacerbation. Two of
      the 13 initially seronegative patients converted to seropositive following acute
      exacerbations. CONCLUSIONS: We established an AQP4-Ab ELISA, which could be a
      potential monitoring tool of disease activity.

PMID- 21965419
TI  - Altered effective connectivity during performance of an information processing
      speed task in multiple sclerosis.
AB  - BACKGROUND: Functional magnetic resonance imaging (fMRI) studies of persons with
      multiple sclerosis (MS) reveal distinct patterns of activation during task
      performance. We were interested in determining whether distinct patterns of
      effective connectivity would be revealed with Granger causality analysis (GCA).
      OBJECTIVE: To characterize directed neural connections in persons with MS during
      a processing speed task between brain regions known to be activated in healthy
      controls. METHODS: fMRI and GCA were used to examine effective connectivity
      underlying performance of a processing speed task in persons with MS. In total,
      16 individuals with MS and 17 healthy controls (HC) performed a modified version
      of the Symbol Digit Modality Task (mSDMT) in the MRI scanner. Eight seed regions
      were selected on the basis of a priori data showing areas involved in mSDMT
      performance of HC. RESULTS: Behaviorally, the MS group attained a level of
      accuracy equivalent to the HC group, although they were significantly slower.
      While there was a great deal of overlap in the connections relied upon by both
      groups, the MS group showed significant differences in connectivity between
      critical brain regions. Specifically, the MS group had more connections from
      multiple regions to frontal cortices bilaterally relative to HCs. CONCLUSIONS:
      Greater neural recruitment by the MS group relative to HC is consistent with the
      neural efficiency hypothesis, and lends further support to the notion that more
      connections must be recruited to maintain performance in the presence of brain
      pathology.

PMID- 21965420
TI  - Telemedicine for multiple sclerosis patients: assessment using Health Value
      Compass.
AB  - BACKGROUND: Telemedicine carries the potential of improving accessibility to
      health services, especially for disabled people. OBJECTIVE: To assess the health
      related outcomes of short-term implementation of telemedicine (telemed) for MS
      patients. METHODS: A prospective study of 40 MS patients divided into a control
      group and a telemed group was conducted, in two stages: A. Six months' follow-up
      for measurement of baseline health-related variables; B. Implementation stage,
      adding home telecare to the telemed group. A Health Value Compass was applied to
      assess the outcomes of home telecare implementation. Clinical status, cost data,
      patients' self-assessment of Health Related Quality of Life (HRQoL) and
      satisfaction with telecare were studied. RESULTS: Patients in the telemed group
      demonstrated improved clinical outcome measured by symptoms severity. There was a
      decrease of at least 35% in the medical costs for 67% of the telemed group
      patients. Satisfaction with telecare was high and most patients would recommend
      this service to others. CONCLUSIONS: The present pilot study, applying Health
      Value Compass-based analysis, suggests that telecare is a powerful tool for
      monitoring MS patients at home, carries the potential to improve health care
      while reducing costs, and should be considered for implementation as part of the
      management of chronic neurological diseases.

PMID- 21965421
TI  - Cortical dysfunction underlies disability in multiple sclerosis.
AB  - BACKGROUND: Gray matter atrophy has been implicated in the development of
      secondary progressive multiple sclerosis (SPMS). Cortical function may be
      assessed by transcranial magnetic stimulation (TMS). Determining whether cortical
      dysfunction was a feature of SPMS could be of pathophysiological significance.
      OBJECTIVES: Consequently, novel paired-pulse threshold tracking TMS techniques
      were used to assess whether cortical dysfunction was a feature of SPMS. METHODS:
      Cortical excitability studies were undertaken in 15 SPMS, 25 relapsing-remitting
      MS patients (RRMS) and 66 controls. RESULTS: Short interval intracortical
      inhibition (SPMS 3.0 +/- 2.1%; RRMS 12.8 +/- 1.7%, p < 0.01; controls 10.5 +/-
      0.7%, p < 0.01) and motor evoked potential (MEP) amplitude (SPMS 11.5 +/- 2.2%;
      RRMS 26.3 +/- 3.6%, p <0.05; controls 24.7 +/- 1.8%, p < 0.01) were reduced in
      SPMS, while intracortical facilitation (SPMS -5.2 +/- 1.9%; RRMS -2.0 +/- 1.4, p
      < 0.05; controls -0.9 +/- 0.7, p < 0.01) and resting motor threshold were
      increased (SPMS 67.5 +/- 4.5%; RRMS 56.0 +/- 1.5%, p < 0.01; controls 59.0 +/-
      1.1%, p < 0.001). Further, central motor conduction time was prolonged in SPMS
      (9.1 +/- 1.2 ms, p < 0.001) and RRMS (7.0 +/- 0.9 ms, p < 0.05) patients compared
      with controls (5.5 +/- 0.2 ms). The observed changes in cortical function
      correlated with the Expanded Disability Status Scale. CONCLUSION: Together, these
      findings suggest that cortical dysfunction is associated with disability in MS,
      and documentation of such cortical dysfunction may serve to quantify disease
      severity in MS.

PMID- 21965422
TI  - Intrathecal synthesis of IgM measured after a first demyelinating event
      suggestive of multiple sclerosis is associated with subsequent MRI brain lesion
      accrual.
AB  - BACKGROUND: Previous studies have demonstrated that intrathecal synthesis of IgM
      is observed in multiple sclerosis (MS) and correlates with a worse disease
      course. These results suggest that IgM participates in the formation of MS
      lesions. OBJECTIVE: The aim of the present study was to assess the potential
      association between the level of intrathecal synthesis of IgM measured after a
      clinically isolated syndrome (CIS) and the subsequent formation of brain lesions.
      METHODS: Fifty seven patients with a CIS and a high risk developing MS were
      enrolled in a longitudinal study. Examination of cerebrospinal fluid was
      performed after the CIS and included measures of intrathecal IgM and IgG
      synthesis. Patients were assessed with the same 1.5 Tesla magnetic resonance
      imaging (MRI) system at baseline and after a mean follow-up period of 49 months
      (range 36-60). Spearman Rank correlation was used to assess the potential
      correlations between levels of intrathecal immunoglobulin synthesis and MRI data.
      RESULTS: The level of intrathecal IgM synthesis was correlated with the number of
      gadolinium-enhancing lesions at baseline (p = 0.01) and with accrual of brain
      lesions during the follow-up period (p = 0.02). By taking into account brain sub
      regions, we demonstrated that the level of intrathecal IgM synthesis was only
      correlated with the increased number of lesions in the periventricular regions (p
      = 0.004). The level of intrathecal IgG synthesis was not correlated with any MRI
      data. CONCLUSION: The present longitudinal study demonstrates that the level of
      intrathecal IgM synthesis measured after a CIS is associated with subsequent
      lesion accrual during the first years of MS. This result emphasizes the
      involvement of IgM in plaque formation.

PMID- 21965423
TI  - Change in disability profile and quality of life in multiple sclerosis patients:
      a five-year longitudinal study using the Multiple Sclerosis Impact Profile
      (MSIP).
AB  - BACKGROUND: Evidence on the progress of disease severity in multiple sclerosis
      (MS) is generally limited in scope. OBJECTIVES: To examine the course of a broad
      spectrum of MS-related disabilities and quality of life (QOL) in relation to
      disease severity, and responsiveness of the Multiple Sclerosis Impact Profile
      (MSIP). METHODS: The mortality rate was calculated after checking the national
      population register for vital status of the initial cohort. We performed a
      longitudinal study among 245 patients with MS attending the Groningen MS Center
      in the Netherlands. We assessed these patients in 2004 and 2009 using a postal
      survey including the MSIP to evaluate disabilities, the World Health Organization
      Quality of Life-Abbreviation version (WHOQOL-BREF) to evaluate QOL, and the
      ambulation question of the Expanded Disability Status Scale (EDSS) to evaluate
      disease severity. Responsiveness of the MSIP was estimated using standardized
      response mean (SRM). RESULTS: Increase of disability in the MSIP disability
      domains and loss of QOL were most prevalent and pronounced in patients with EDSS
      0 to < 4.5 in 2004. MSIP and QOL scores were remarkably stable in the higher
      disease severity groups. Mortality rates were highest (24%) in patients with EDSS
      >= 7 to < 10 in 2004. SRM indices for the MSIP ranged between 0.26 and 0.56.
      CONCLUSIONS: Prominent increases in multiple aspects of disability and loss of
      QOL occur especially in the early stages in MS. Health care interventions may
      lead to health and QOL gains, in particular when offered to patients in the first
      stage of the MS process. Responsiveness was sufficient for nine of the 11 MSIP
      domains.

PMID- 21965424
TI  - Cost of multiple sclerosis in the Czech Republic: the COMS study.
AB  - BACKGROUND: Information about cost of multiple sclerosis (MS) is available from a
      number of European countries, but no data from the Czech Republic have been
      published so far. OBJECTIVE: The objective of this study was to establish the
      cost of MS in the Czech Republic, overall and by level of disease severity.
      METHODS: Data on demographics, disease history, resource consumption and
      production losses were collected from 909 patients recruited in 7 MS centres in
      the Czech Republic. Annual costs were estimated in the societal perspective,
      using 2007 unit costs. To evaluate the relationship between disability and costs,
      patients were stratified into those with mild (67%), moderate (27%) and severe
      (10%) disability using the Expanded Disability Status Scale. RESULTS: Mean total
      annual costs per patient were ?12,272, of which 51% were direct medical costs, 4%
      direct non-medical costs and 45% indirect costs. The average annual costs in
      patients with mild, moderate and severe disability amounted to ?9905, ?14,064 and
      ?22,880, respectively. CONCLUSION: The total costs of MS in the Czech Republic
      are estimated at ?208.6 million per year. Consistent with other studies, the
      costs increase significantly with the severity of MS.

PMID- 21965425
TI  - Impact of socioeconomic factors on in-patient length of stay and their
      consequences in per case hospital payment systems.
AB  - OBJECTIVES: The number of countries adopting per case hospital payment systems
      has been continuously increasing in recent years. Nonetheless, debates persist
      regarding their consequences for equity of access to services. This concern
      relates to the failure of diagnostic classifications properly to take into
      account patients' care requirements, raising the threat of case selection ('cream
      skimming'). We examine the heterogeneity of costs within diagnostic categories
      related to socioeconomic (SE) factors using length of stay (LOS) as a proxy
      measure of care needs and costs. We evaluate its consequences in terms of
      fairness in resource allocation between hospitals. METHODS: We employ data on all
      discharges in 2002-03 from a sample of 60 Belgian hospitals (617,275
      observations), measuring the association between LOS and SE factors using
      generalized linear models. We design a resource allocation formula based on the
      Belgian financing scheme, where non-medical activity is paid based on a normative
      number of in-patient days, and measure financial penalties and rewards according
      to whether payment is adjusted for the SE characteristics of patients or not.
      RESULTS: Both patients' SE status and hospitals' area SE profile have a
      significant impact on LOS, which persists after controlling for detailed
      diagnostic and hospital characteristics. Hospitals treating low income patients
      are financially penalized as a result. CONCLUSION: SE factors are a predictor of
      in-patient LOS and should be taken into account in per case resource allocation
      among hospitals.

PMID- 21965426
TI  - How do we know when research from one setting can be useful in another? A review
      of external validity, applicability and transferability frameworks.
AB  - OBJECTIVE: To review published frameworks that included criteria for the
      assessment of external validity, applicability and transferability in their
      assessment of health research. METHODS: Five databases were searched for articles
      relating to the assessment of external validity or applicability and
      transferability in health research. A coding framework was developed inductively
      and used to assess which types of criteria were included in the frameworks.
      RESULTS: Thirty-eight articles describing 25 frameworks were identified. Eleven
      focused solely on the assessment of applicability and transferability; 14
      presented more general decision-making or evidence appraisal frameworks. The
      criteria were synthesized into four main categories: setting, intervention,
      outcomes and evidence. None of the frameworks covered all the criteria
      identified. A major limitation was the lack of empirical data used to develop
      many frameworks and the apparent lack of assessment of their perceived utility.
      CONCLUSION: A validated framework of applicability and transferability would help
      those aiming to encourage research use, as well as those conducting research.
      Greater understanding of applicability and transferability could help to
      encourage the appropriate use of research and the development of research that is
      more useful.

PMID- 21965428
TI  - Impact of the French campaign to reduce inappropriate ambulatory antibiotic use
      on the prescription and consultation rates for respiratory tract infections.
AB  - OBJECTIVES: To assess long-term trends in the volume of ambulatory antibiotic
      prescriptions and prescription and consultation rates for respiratory tract
      infections (RTIs) in France in relation to the yearly public antibiotic campaign
      since 2002. METHODS: Data collected on representative cohorts of office-based
      physicians and pharmacies in France participating in IMS Health panels between
      1980 and 2009 were analysed retrospectively. Main outcome measures were
      antibiotic prescriptions per 1000 inhabitants per year (PIY), consultations per
      1000 inhabitants per year and proportion of consultations resulting in antibiotic
      prescriptions. RESULTS: The peak in ambulatory antibiotic prescriptions occurred
      in 1997 (1468 PIY). Although prescriptions had decreased by 6% until 2001,
      prescriptions fell sharply (-22%) between 2001 and 2004, followed by stable
      prescription rates until 2009. The 2001-09 decrease in antibiotic prescriptions
      was driven by a sharp decline in office-based antibiotic prescriptions (-33%),
      exclusively achieved through a decrease in prescriptions for RTIs. Consultations
      for RTIs steadily declined between 2001 and 2009 (-23%), with the proportion of
      consultations resulting in antibiotic prescriptions decreasing from 58% to 46%.
      Not all types of RTIs were equally affected. The largest decrease in
      prescriptions was observed for nasopharyngitis and influenza. Rates for
      bronchitis, sinusitis, otitis media and tonsillitis remained persistently high.
      CONCLUSIONS: During its first 3 years, the French public campaign accelerated a
      pre-existing decrease in ambulatory antibiotic prescriptions. The decrease in
      consultation rates suggests that altered illness behaviour of patients may have
      contributed to the observed decline. The persistently high prescribing rates for
      certain RTIs show that further effort is needed to improve antibiotic prescribing
      in France.

PMID- 21965429
TI  - Tn1548-associated armA is co-located with qnrB2, aac(6')-Ib-cr and blaCTX-M-3 on
      an IncFII plasmid in a Salmonella enterica subsp. enterica serovar Paratyphi B
      strain isolated from chickens in China.

PMID- 21965430
TI  - AbaR-type transposon structures in Acinetobacter baumannii.

PMID- 21965431
TI  - Automated quantitative drug susceptibility testing of non-tuberculous
      mycobacteria using MGIT 960/EpiCenter TB eXiST.
AB  - OBJECTIVES: To assess the predictive value of in vitro drug susceptibility
      testing (DST) in slow-growing non-tuberculous mycobacteria (NTM), knowledge on
      quantitative levels of drug susceptibility should be available. The aim of this
      study was to investigate the suitability of the MGIT 960/TB eXiST system for
      quantitative DST of NTM. METHODS: We have assessed quantitative levels of drug
      susceptibility for clinical isolates of Mycobacterium avium, Mycobacterium
      intracellulare and Mycobacterium kansasii by comparing radiometric Bactec 460TB
      based DST with non-radiometric DST using MGIT 960/TB eXiST. RESULTS: MGIT 960/TB
      eXiST gives results comparable to those of Bactec 460TB. CONCLUSIONS: The MGIT
      960/TB eXiST appears suitable for quantitative DST of NTM.

PMID- 21965433
TI  - Antiviral effect of raltegravir on HTLV-1 carriers.
AB  - BACKGROUND: In vitro studies support that integrase inhibitors, such as
      raltegravir, may inhibit human T cell lymphotropic virus type 1 (HTLV-1)
      replication. However, this hypothesis has not been tested in vivo. METHODS: HTLV
      1-infected individuals were invited to participate in a pilot, open study that
      examined whether 400 mg of raltegravir twice daily could exhibit any recognizable
      virological effect over 12 months. Proviral DNA was measured by a real-time PCR
      targeting the pol region. HTLV-1 integrase sequences were obtained from
      peripheral blood mononuclear cells (PBMCs) at baseline and during follow-up.
      RESULTS: A total of five HTLV-1-infected individuals entered the study. All were
      infected with HTLV-1 subtype a. Two patients had HTLV-1-associated
      myelopathy/tropical spastic paraparesis (HAM/TSP), the rest being asymptomatic.
      The HTLV-1 proviral load was high in all cases (median 758 HTLV-1 DNA
      copies/10(4) PBMCs). Following the initiation of raltegravir therapy and for up
      to 6 months, both of the HAM/TSP patients experienced a transient decline in the
      HTLV-1 proviral load (2248 to 519 and 1033 to 861 copies/10(4) PBMCs,
      respectively), returning to baseline levels on subsequent determinations. No
      significant changes in the HTLV-1 proviral load were noticed in the three
      asymptomatic individuals (median proviral load of 755 copies/10(4) PBMCs over
      time). A total of 20 integrase sequences could be obtained from the five
      patients, and no genotypic substitutions were recognized comparing baseline and
      follow-up specimens under raltegravir. CONCLUSIONS: Treatment with raltegravir in
      HTLV-1-infected individuals does not result in a significant reduction of
      proviral load beyond 6 months of therapy. The lack of continuous viral
      replication cycles in chronic HTLV-1 carriers most likely explains our findings.

PMID- 21965434
TI  - Rhabdomyolysis associated with the co-administration of daptomycin and pegylated
      interferon alpha-2b and ribavirin in a patient with hepatitis C.

PMID- 21965435
TI  - Nucleoside/nucleotide analogues in the treatment of chronic hepatitis B.
AB  - The current available agents for the treatment of chronic hepatitis B (CHB)
      include immunomodulatory agents, such as interferon-alpha and pegylated
      interferon-alpha, and oral nucleoside/nucleotide analogues (NAs), including
      lamivudine, adefovir, telbivudine, entecavir and tenofovir. The NAs work mainly
      by inhibiting hepatitis B virus (HBV) DNA polymerase activity and thus suppress
      HBV replication. Oral NAs have become the mainstay of CHB treatment, mainly due
      to their profound viral suppressive effects and also due in part to the ease of
      single daily dosing and lack of significant side effects. One major drawback of
      NA therapy is the development of drug resistance mutations with long-term
      treatment. Lamivudine, the first oral NA approved for CHB patients, is associated
      with high rates of drug resistance, with resultant virological relapse and
      biochemical flare. Fortunately, newer and more potent NAs, such as entecavir and
      tenofovir, have very low resistance rates, with potent and durable viral
      suppression. This review is aimed at the current developments in NAs for CHB
      treatment, detailing the mechanisms of antiviral activity of the different
      agents, the efficacy of viral suppression, the achievement of treatment
      endpoints, the development of drug resistance and the optimal strategies for
      using these drugs.

PMID- 21965432
TI  - Effect of accompanying antiretroviral drugs on virological response to pegylated
      interferon and ribavirin in patients co-infected with HIV and hepatitis C virus.
AB  - OBJECTIVES: The effects of antiretroviral drugs on the response to pegylated
      interferon plus ribavirin remain uncertain. We evaluated whether antiretroviral
      drugs affected the response to pegylated interferon plus ribavirin in patients co
      infected with HIV and hepatitis C virus (HCV). METHODS: We conducted a
      retrospective analysis of two cohorts of HIV/HCV-co-infected patients treated
      with pegylated interferon plus ribavirin between 2001 and 2007 in Spain. The
      outcome measure was sustained virological response (SVR). Logistic regression
      models were used to test possible associations between non-response and pre
      treatment characteristics, including accompanying antiretroviral drugs. RESULTS:
      The study sample comprised 1701 patients: 63% were infected with HCV genotype (G)
      1 or 4 and 88% were taking highly active antiretroviral therapy (HAART). Factors
      independently associated with increased odds of SVR were G2 or 3, HVC RNA
      <500,000 IU/mL and CDC clinical category A or B. When we adjusted for these
      prognostic factors and dose of ribavirin/kg, the adjusted odds ratio (AOR) of SVR
      for patients without HAART was 1.31 [95% confidence interval (CI) 0.91-1.88; P =
      0.144]. Taking the backbone of tenofovir and lamivudine/emtricitabine as a
      reference, we found that, with the exception of regimens including zidovudine,
      the effect of other nucleoside reverse transcriptase inhibitor backbones had
      little effect on SVR. The AOR of SVR for zidovudine and lamivudine was 0.65 (95%
      CI 0.46-0.93, P = 0.017). We carried out several sensitivity analyses, the
      results of which were consistent with the findings of the primary analysis.
      CONCLUSIONS: Our results suggest that, with the exception of regimens including
      zidovudine, accompanying antiretroviral drugs have little effect on the
      virological response to pegylated interferon plus ribavirin in HIV/HCV-co
      infected patients.

PMID- 21965436
TI  - Antimicrobial susceptibility of Helicobacter pylori to six antibiotics currently
      used in Spain.
AB  - BACKGROUND: Antibiotic resistance is directly related to the loss of efficacy of
      currently accepted Helicobacter pylori therapies. Knowledge of the antibiotic
      susceptibility in a local area can contribute to the design of specific 'a la
      carte' treatments. The aim of this study was to analyse the susceptibility of H.
      pylori isolates to six conventional antibiotics currently used in a northern
      region of Spain. METHODS: Seventy-one isolates were obtained from gastric
      biopsies of 76 consecutive adult patients suffering from peptic ulcer disease,
      dyspepsia or familial gastric cancer and known to be infected with H. pylori by
      conventional methods. Susceptibility testing was performed for amoxicillin,
      ciprofloxacin, levofloxacin, clarithromycin, metronidazole and tetracycline using
      the Etest method. RESULTS: The prevalence rates of resistance were as follows:
      amoxicillin, 1.4% [95% confidence interval (CI) 0.0-7.6]; clarithromycin, 14.7%
      (95% CI 7.3-25.4); ciprofloxacin, 14.3% (95% CI 7.1-24.7); levofloxacin, 14.5%
      (95% CI 7.2-25.0); metronidazole, 45.1% (95% CI 33.2-57.3); and tetracycline, 0%
      (95% CI 0.0-5.1). CONCLUSIONS: Our study confirms an increasing rate of
      resistance to levofloxacin that equals that of clarithromycin in our healthcare
      area. This fact may reflect a wide and indiscriminate use of the former
      antibiotic and could account for a loss of clinical effectiveness of levofloxacin
      containing regimens. Moreover, clarithromycin resistance rates remain stable,
      which could allow us to maintain its use in our area.

PMID- 21965437
TI  - Inadvertent intrathecal administration of vincristine: has anything changed?

PMID- 21965439
TI  - Separable neural bases for subprocesses of recognition in working memory.
AB  - Working memory supports the recognition of objects in the environment. Memory
      models have postulated that recognition relies on 2 processes: assessing the
      degree of similarity between an external stimulus and memory representations and
      testing the resulting summed-similarity value against a critical level for
      recognition. Here, we varied the similarity between samples held in working
      memory and a probe to investigate these 2 processes with magnetoencephalography.
      Two separable components matched our expectations: First, from 280 ms after probe
      onset, clearly nonmatching probes differed from both similar nonmatches and
      matches over left frontal cortex. At 350-400 ms, these signals evolved into a
      pattern of gradually increasing activation as a function of sample-probe
      similarity, as expected for a neural representation of summed similarity. Second,
      a signal potentially reflecting criterion testing was observed at 600-700 ms at
      right frontotemporal sensors that differentiated between matches and nonmatches
      without further differences between similar and dissimilar probes. Thus, analysis
      of the time course of recognition provided strong evidence that similarity
      summation and criterion testing have separable neural bases. As probably both
      working and long-term memory recognition draw on these processes, they may be
      involved in many domains of behavior.

PMID- 21965438
TI  - Decreased cortical thickness in central hypoventilation syndrome.
AB  - Central hypoventilation syndrome (CHS) is a rare condition characterized by
      hypoventilation during sleep, reduced ventilatory responsiveness to CO(2) and
      O(2), impaired perception of air hunger, and autonomic abnormalities. Neural
      impairments accompany the condition, including structural injury, impaired
      cerebral autoregulation, and dysfunctional autonomic control. The hypoventilation
      may induce cortical hypoxic injury, additional to consequences of maldevelopment
      from PHOX2B mutations present in most CHS subjects. We assessed cortical injury
      in clinically diagnosed CHS using high-resolution magnetic resonance imaging
      scans, collected from 14 CHS (mean age +/- standard deviation [SD] 17.7 +/- 5.0
      years; 6 female) and 29 control (mean age +/- SD, 17.9 +/- 4.3 years; 12 female)
      subjects. We measured group differences in mean cortical thickness and age
      thickness correlations using FreeSurfer software, accounting for age and sex (0.1
      false discovery rate). Reduced thickness in CHS appeared in the dorsomedial
      frontal cortex and anterior cingulate; medial prefrontal, parietal, and posterior
      cingulate cortices; the insular cortex; anterior and lateral temporal lobes; and
      mid- and accessory motor strips. Normal age-related cortical thinning in multiple
      regions did not appear in CHS. The cortical thinning may contribute to CHS
      cardiovascular and memory deficits and may impair affect and perception of
      breathlessness. Extensive axonal injury in CHS is paralleled by reduced cortical
      tissue and absence of normal developmental patterns.

PMID- 21965440
TI  - Mental addition in bilinguals: an FMRI study of task-related and performance
      related activation.
AB  - Behavioral studies show that bilinguals are slower and less accurate when
      performing mental calculation in their nondominant (second; L2) language than in
      their dominant (first; L1) language. However, little is known about the neural
      correlates associated with the performance differences observed between
      bilinguals' 2 languages during arithmetic processing. To address the cortical
      activation differences between languages, the current study examined task-related
      and performance-related brain activation during mental addition when problems
      were presented auditorily in participants' L1 and L2. Eleven Chinese-English
      bilinguals heard 2-digit addition problems that required exact or approximate
      calculations. Functional magnetic resonance imaging results showed that
      auditorily presented multidigit addition in bilinguals activates bilateral
      inferior parietal and inferior frontal regions in both L1 and L2. Language
      differences were observed in the form of greater activation for L2 exact addition
      in the left inferior frontal area. A negative correlation between brain
      activation and behavioral performance during mental addition in L2 was observed
      in the left inferior parietal area. Current results provide further evidence for
      the effects of language-specific experience on arithmetic processing in
      bilinguals at the cortical level.

PMID- 21965441
TI  - Descending systems translate transient cortical commands into a sustained muscle
      activation signal.
AB  - Controlling motor actions requires online adjustments of time-varying parameters.
      Although numerous studies have attempted to identify the parameters coded in
      different motor sites, the relationships between the temporal profile of neuronal
      responses and the dynamics of motor behavior remain poorly understood in
      particular because motor parameters such as force and movement direction often
      change over time. We studied time-dependent coding of cortical and spinal neurons
      in primates performing an isometric wrist task with an active hold period, which
      made it possible to segregate motor behavior into its phasic and sustained
      components. Here, we show that cortical neurons transiently code motor-related
      parameters when actively acquiring a goal, whereas spinal interneurons provide
      persistent information regarding maintained torque level and posture. Moreover,
      motor cortical neurons differed substantially from spinal neurons with regard to
      the evolvement of parameter-specific coding over the course of a trial. These
      results suggest that the motor cortex and spinal cord use different control
      policies: Cortical neurons produce transient motor commands governing ensuing
      actions, whereas spinal neurons exhibit sustained coding of ongoing motor states.
      Hence, motor structures downstream to M1 need to integrate cortical commands to
      produce state-dependent spinal firing.

PMID- 21965442
TI  - Separability and commonality of auditory and visual bistable perception.
AB  - It is unclear what neural processes induce individual differences in perceptual
      organization in different modalities. To examine this issue, the present study
      used different forms of bistable perception: auditory streaming, verbal
      transformations, visual plaids, and reversible figures. We performed factor
      analyses on the number of perceptual switches in the tasks. A 3-factor model
      provided a better fit to the data than the other possible models. These factors,
      namely the "auditory," "shape," and "motion" factors, were separable but
      correlated with each other. We compared the number of perceptual switches among
      genotype groups to identify the effects of neurotransmitter functions on the
      factors. We focused on polymorphisms of catechol-O-methyltransferase (COMT)
      Val(158)Met and serotonin 2A receptor (HTR2A) -1438G/A genes, which are involved
      in the modulation of dopamine and serotonin, respectively. The number of
      perceptual switches in auditory streaming and verbal transformations differed
      among COMT genotype groups, whereas that in reversible figures differed among
      HTR2A genotype groups. The results indicate that the auditory and shape factors
      reflect the functions of the dopamine and serotonin systems, respectively. Our
      findings suggest that the formation and selection of percepts involve neural
      processes in cortical and subcortical areas.

PMID- 21965443
TI  - Mirror biofeedback rehabilitation after administration of single-dose botulinum
      toxin for treatment of facial synkinesis.
AB  - OBJECTIVE: The efficacy of facial biofeedback rehabilitation with a mirror after
      administration of a single dose of botulinum A toxin on facial synkinesis was
      examined in patients with chronic facial palsy. STUDY DESIGN: Prospective
      clinical study. SETTING: University hospital. SUBJECTS AND METHODS: The present
      study includes 8 patients with Bell palsy and 5 with herpes zoster oticus showing
      facial synkinesis. A single dose of botulinum A toxin was used as the initial
      process of facial rehabilitation. Patients then continued a daily facial
      biofeedback rehabilitation with a mirror at home. They were instructed to keep
      their eyes symmetrically open using a mirror during mouth movements. The degree
      of oral-ocular synkinesis was evaluated by the degree of asymmetry of eye opening
      width during mouth movements (% eye opening). RESULTS: After administration of a
      single dose of botulinum A toxin, temporary relief of facial synkinesis was
      observed in all patients. Patients were then instructed to continue the facial
      biofeedback rehabilitation with a mirror for 10 months. The mean values of the
      percent of eye opening during 3 designated mouth movements that included lip
      pursing /u:/, teeth baring /i:/, and cheek puffing /pu:/ increased significantly
      after 10 months when the effects of botulinum A toxin had completely disappeared.
      CONCLUSION: These findings demonstrate that facial biofeedback rehabilitation
      with a mirror after administration of a single dose of botulinum A toxin is a
      long-lasting treatment of established facial synkinesis in patients with chronic
      facial palsy.

PMID- 21965444
TI  - Simulation in otolaryngology: smart dummies and more.
AB  - Simulation is revolutionizing medical education, certification, and ongoing
      professional development. Simulation encompasses a variety of technologies as
      well as nontechnical approaches to improve individual psychomotor skills, group
      effectiveness, and systems processes, all without direct risk to patients.
      Simulation-enhanced learning experiences, addressing learning objectives based on
      the needs of the individual or the group and following the principles of adult
      education, can be used to ensure consistent and comprehensive learning
      opportunities, thereby creatively complementing didactic and clinical learning
      experiences. Pockets of simulation expertise are already present in the field of
      otolaryngology; more will develop as these exciting and important innovations
      blossom.

PMID- 21965445
TI  - Septoplasty improves life quality related to allergy in patients with septal
      deviation and allergic rhinitis.
AB  - OBJECTIVE: Evaluate the effect of septoplasty on the clinical course of allergic
      rhinitis by comparing (1) symptom change using the Visual Analogue Scale (VAS),
      (2) change of the medication score, and (3) improvement of the quality of life
      using a questionnaire. STUDY DESIGN: Prospective pilot. SETTING: Academic
      tertiary rhinological practice. SUBJECTS AND METHODS: Sixty-two patients who had
      undergone septoplasty and turbinoplasty for septal deviation and allergic
      rhinitis were enrolled in group A. Twenty-six patients who had undergone only
      turbinoplasty for allergic rhinitis were enrolled in group B. The VAS score, the
      Average Rescue Medication Score (ARMS), and the Rhinasthma Questionnaire for the
      quality of life were all obtained from each patient. These parameters were
      compared before and after the surgery and between the groups. RESULTS: Both
      groups showed significant improvement of the VAS score (P < .001). When the
      change of VAS was compared between groups, there was a significant difference in
      group A only for nasal obstruction (P = .047). Comparison of the ARMS between
      groups showed significant improvement in both groups after the surgery (P < .01).
      However, there were no differences between the groups. The Rhinasthma score of
      group A was significantly lowered after the surgery (56.4 +/- 13.2 to 34.1 +/-
      12.3, P < .001). The Rhinasthma score of group A was significantly lower than
      that of group B after the surgery (P = .004). CONCLUSIONS: This is the first
      research about the potential effect of septoplasty on the clinical course of
      allergic rhinitis. Further studies are needed to elucidate the mechanisms
      underlying these effects.

PMID- 21965446
TI  - Organic and inorganic selenium: II. Transfer efficiency from ewes to lambs.
AB  - Adequate Se transfer from ewes to lambs is important to prevent Se-deficiency
      diseases. To evaluate how different chemical forms of Se administered at
      comparative dosages to mature ewes affect Se status of their lambs, 240 ewes were
      divided into 8 treatment groups (n = 30 each) and drenched weekly (at an amount
      equal to their summed daily intake) with no-Se (controls); at recommended amounts
      (4.9 mg of Se/wk) with inorganic Na-selenite, inorganic Na-selenate, or organic
      Se-yeast; or at supranutritional amounts (14.7 and 24.5 mg of Se/wk) with Na
      selenite or Se-yeast for 1 yr. Weekly drenching of Se was effective at increasing
      (P < 0.002) Se concentrations in ewe colostrum and milk at 30 d of lactation and
      in improving (P < 0.001) the Se status of lambs (whole-blood and serum-Se
      concentrations at birth, and skeletal-muscle Se concentrations at 14 d of age).
      Selenium concentrations in lacteal secretions were greater in ewes drenched with
      Se-yeast (colostrum: 374, 436, and 982 ng/mL at 4.9, 14.7, and 24.5 mg of Se/wk,
      respectively; milk: 26, 39, 64 ng/mL) compared with ewes drenched with Na
      selenite (colostrum: 204, 334, 428 ng/mL; milk: 16, 21, 24 ng/mL), and were also
      greater (P < 0.001) in their lambs. Selenium concentrations continued to increase
      (P < 0.001) in lamb whole blood (558 and 695 ng/mL at 14.7 and 24.5 mg of Se/wk,
      respectively), serum (126, 183 ng/mL), and skeletal muscle (991, 1,696 ng/mL)
      with supranutritional concentrations of Se-yeast, whereas Se concentrations did
      not differ in whole blood (304, 332 ng/mL), serum (77, 85 ng/mL), or skeletal
      muscle (442, 482 ng/mg) of lambs from ewes drenched with 14.7 or 24.5 mg of Se/wk
      of Na-selenite. We conclude that weekly oral drenching of ewes during gestation
      and lactation with organic Se-yeast results in a more efficient transfer of Se
      (over a wide range of supplementation rates) from ewe to lamb than does inorganic
      Na-selenite.

PMID- 21965447
TI  - Physiology and Endocrinology Symposium: Nutritional aspects of developing
      replacement heifers.
AB  - Studies in numerous species provide evidence that diet during development can
      mediate physiological changes necessary for puberty. In cattle, several studies
      have reported inverse correlations between postweaning growth rate and age at
      puberty and heifer pregnancy rates. Thus, postweaning growth rate was determined
      to be an important factor affecting age of puberty, which in turn influences
      pregnancy rates. This and other research conducted during the late 1960s through
      the early 1980s indicated puberty occurs at a genetically predetermined size, and
      only when heifers reach their target BW can increased pregnancy rates be
      obtained. Guidelines were established indicating replacement heifers should
      achieve 60 to 65% of their expected mature BW by breeding. Traditional approaches
      for postweaning development of replacement heifers used during the last several
      decades have primarily focused on feeding heifers to achieve or exceed an
      appropriate target BW and thereby maximize heifer pregnancy rates. Intensive
      heifer development systems may maximize pregnancy rates, but not necessarily
      optimize profit or sustainability. Since inception of target BW guidelines,
      subsequent research demonstrated that the growth pattern heifers experience
      before achieving a critical target BW could be varied. Altering rate and timing
      of BW gain can result in compensatory growth periods, providing an opportunity to
      decrease feed costs. Recent research has demonstrated that feeding replacement
      heifers to traditional target BW increased development costs without improving
      reproduction or subsequent calf production relative to development systems in
      which heifers were developed to lighter target BW ranging from 50 to 57% of
      mature BW.

PMID- 21965448
TI  - Effects of dietary supplementation with an organic source of selenium on
      characteristics of semen quality and in vitro fertility in boars.
AB  - Semen characteristics in boars fed organic or inorganic sources of Se were
      assessed in 3 experiments. Crossbred boars were randomly assigned at weaning to 1
      of 3 dietary treatments: I) basal diets with no supplemental Se (control), II)
      basal diets with 0.3 mg/kg of supplemental Se from an organic source (Sel-Plex,
      Alltech Inc., Nicholasville, KY), and III) basal diets supplemented with 0.3
      mg/kg of supplemental Se from sodium selenite (Premium Selenium 270, North
      American Nutrition Co. Inc., Lewisburg, OH). For Exp. 1, semen was collected from
      boars (n = 10/dietary treatment) on 5 consecutive days at 15 mo of age. Effects
      of treatment * day were detected for the proportions of progressively motile (P =
      0.02) and rapidly moving (P = 0.03) spermatozoa, and measures of sperm velocity,
      including path velocity of the smoothed cell path (P = 0.05) and average velocity
      measured in a straight line from the beginning to the end of the track (P =
      0.05). Negative effects of day of semen collection on sperm motility were least
      pronounced in boars fed Sel-Plex. Experiment 2 was conducted when boars were 17
      mo of age, and semen was collected (n = 10 boars/dietary treatment), diluted in
      commercially available extenders, and stored at 18 degrees C for 9 d. Effects of
      treatment * day were detected for percentages of motile (P = 0.01) and static (P
      = 0.01) spermatozoa, amplitude of lateral head displacement (P = 0.02), frequency
      with which the sperm track crossed the sperm path (P = 0.04), straightness (P =
      0.01), and average size of all sperm heads (P = 0.03). In general, sperm cells
      from boars fed Sel-Plex were better able to maintain motility during liquid
      storage compared with boars fed sodium selenite. For Exp. 3, semen was collected
      from boars (n = 6/dietary treatment) at 23 mo of age, and spermatozoa were
      evaluated at d 1 and 8 after semen collection using in vitro fertilization
      procedures. There was a tendency for an effect (P = 0.11) of dietary treatment on
      fertilization rate with Sel-Plex-fed boars having the greatest value (70.7%). The
      results of this study suggest that there are positive effects of dietary
      supplementation with Sel-Plex on boar semen characteristics and that organic Se
      supplementation may help ameliorate the negative effects of semen storage on
      characteristics of sperm motility.

PMID- 21965449
TI  - Meat Science and Muscle Biology Symposium: the influence of extracellular matrix
      on intramuscular and extramuscular adipogenesis.
AB  - The extracellular matrix (ECM) and specific ECM components can have a major
      influence on cell growth, development, and phenotype. The influence of the ECM
      and ECM components on adipogenesis in vivo and in vitro will be reviewed in this
      paper. Engelbreth-Holm-Swarm substratum and laminin per se markedly increased
      attachment, spreading, and hypertrophy of preadipocytes in serum-free primary
      cultures of porcine adipose tissue stromal-vascular cells. Furthermore, primary
      cultures of stromal-vascular cells showed that preadipocytes express ECM
      components after preadipocyte recruitment. Staining for plant lectins, type IV
      collagen, and laminin in fetal pig adipose tissue demonstrates that adipocyte
      reactivity for laminin was strong throughout fetal development and was similar
      for developing adipocytes and vasculature. However, lectin binding and type IV
      collagen reactivity of blood vessels preceded that for adipocytes. Therefore,
      these studies indicated that the ECM and in particular laminin may play a
      critical role in morphological aspects of preadipocyte development. Specific
      inhibitors and modulators of collagen synthesis have been used to evaluate the
      role of collagens in the differentiation of bovine intramuscular preadipocytes
      (BIP) and other preadipocyte cell lines. Triglyceride accretion of BIP cells was
      inhibited by a general inhibitor of collagen biosynthesis, whereas specific
      inhibitors or modulators of type IV collagen inhibited 3T3-L1 cell
      differentiation. Further study revealed that compared with collagens types I to
      IV, type V and VI collagens have an important and active role in BIP
      adipogenesis. The growth of intramuscular bovine adipose tissue may be dependent
      on collagen newly synthesized and organized by the adipocytes per se. The role of
      extracellular or ECM proteolysis in regulating adipogenesis also will be reviewed
      in this paper. Many members of the matrix metalloproteinase (MMP) family are
      expressed by adipocytes, and specific inhibition of MMP-9 greatly reduces
      adipogenesis in vitro. Possibly, MMP and other proteases regulate turnover of key
      adipocyte ECM proteins that are involved in the regulation of preadipocyte
      proliferation and differentiation.

PMID- 21965450
TI  - Lactation curve and effects of milking regimen on milk yield and quality, and
      udder health in Martina Franca jennies (Equus asinus).
AB  - Three experiments were conducted on Martina Franca jennies. Experiment 1 tested
      Wood's model for evaluating the lactation curve. Data from the entire lactation
      period of 12 jennies were used. The results showed that Wood's model was able to
      recognize the shape of the lactation curve from pooled data (r(2) = 0.11; P <
      0.01), with the lactation peak occurring at 48 d. Individual curves showed wide
      variability. Experiment 2 aimed to evaluate the effects of the daily number of
      milkings (1, 3, or 6) and the interval between the separation of foals from dams
      and milking (2 or 3 h) on milk yield and udder health. Four groups of jennies (n
      = 5) were considered: 1 * 3H, milked once per day (1*) with a 3-h interval from
      the time of foal removal (3H) from the dams to mechanical milking (3-h interval);
      3 * 3H, milked 3 times per day with 3-h intervals; 3 * 2H, milked 3 times per day
      with 2-h intervals; and 6 * 2H, milked 6 times per day with 2-h intervals. The
      milk somatic cell count (SCC) was monitored. Better efficiency was observed for 3
      vs. 1 milking per day and for 3-h vs. 2-h intervals. The regimen of 6 daily
      milkings at 2-h intervals did not increase milk yield and was related to an
      increase in the SCC compared with 3 daily milkings. In Exp. 3, the effects of the
      interval from foal removal to milking (3, 5, or 8 h) on yield, gross chemical
      composition, organoleptic characteristics of the milk, and udder health of the
      jennies were evaluated. The effects of milking time were also evaluated. Twenty
      jennies milked twice daily (2*) were subdivided into 4 groups (n = 5): 2 * 3H,
      with milkings at 1200 h and 1900 h and an interval of 3 h; 2 * 5H, milked at 1200
      h and 1900 h with a 5-h interval; 2 * 8H(1), milked at 1200 h and 2200 h with an
      8-h interval; and 2 * 8H(2), milked at 0700 h and 1900 h with an 8-h interval.
      Milk yield was greater by 28.4% when an 8-h interval was used compared with a 3-h
      interval and at the morning vs. the evening milking. The milk yield per milking
      was greatest at 0700 h, indicating the existence of a circadian rhythm in milk
      secretion processes. Intervals of 5 and 8 h caused significant decreases in the
      fat and lactose content and organoleptic characteristics of the milk, whereas an
      8-h interval led to an increase in the SCC. In conclusion, a milking regimen of
      twice-daily milking at 0700 h and 1900 h with an 8-h interval provided the
      maximum yield per day. In terms of milk quality, a 3-h interval yielded the best
      results.

PMID- 21965451
TI  - Organic and inorganic selenium: I. Oral bioavailability in ewes.
AB  - Although the essentiality of dietary Se for sheep has been known for decades, the
      chemical source and Se dosage for optimal health remain unclear. In the United
      States, the Food and Drug Administration (FDA) regulates Se supplementation,
      regardless of the source of Se, at 0.3 mg of Se/kg of diet (as fed), which is
      equivalent to 0.7 mg of Se/d or 4.9 mg of Se/wk per sheep. The objectives of this
      study were to evaluate the effects of Se source (inorganic vs. organic) and
      supplementation rate (FDA vs. supranutritional rates of 14.7 and 24.5 mg of
      Se/wk) on whole-blood (WB) and serum-Se concentrations. Mature ewes (n = 240)
      were randomly assigned to 8 treatment groups (n = 30 each) based on Se
      supplementation rate (4.9, 14.7, and 24.5 mg of Se*wk(-1)*sheep(-1)) and source
      [Na-selenite, Na-selenate (4.9 mg/wk only), and organic Se-yeast] with a no-Se
      control group (0 mg of Se/wk). Treatment groups were balanced for healthy and
      footrot-affected ewes. For 1 yr, ewes were individually dosed once weekly with 0,
      4.9, 14.7, or 24.5 mg of Se, quantities equivalent to their summed daily
      supplementation rates. Serum- and WB-Se concentrations were measured every 3 mo
      in all ewes; additionally, WB-Se concentrations were measured once monthly in one
      half of the ewes receiving 0 or 4.9 mg of Se/wk. Ewes receiving no Se showed a
      78.8 and 58.8% decrease (P < 0.001) in WB- (250 to 53 ng/mL) and serum- (97 to 40
      ng/mL) Se concentrations, respectively, over the duration of the study. Whole
      blood Se decreased primarily during pregnancy (-57%; 258 to 111 ng/mL) and again
      during peak lactation (-44%; 109 to 61 ng/mL; P < 0.001). At 4.9 mg of Se/wk, Se
      yeast (364 ng/mL, final Se concentration) was more effective than Na-selenite
      (269 ng/mL) at increasing WB-Se concentrations (P < 0.001). Supranutritional Se
      yeast dosages increased WB-Se concentrations in a dose-dependent manner (563
      ng/mL, 14.7 mg of Se/wk; 748 ng/mL, 24.5 mg of Se/wk; P < 0.001), whereas WB-Se
      concentrations were not different for the Na-selenite groups (350 ng/mL, 14.7 mg
      of Se/wk; 363 ng/mL, 24.5 mg of Se/wk) or the 4.9 mg of Se/wk Se-yeast group (364
      ng/mL). In summary, the dose range whereby Se supplementation increased blood Se
      concentrations was more limited for inorganic Na-selenite than for organic Se
      yeast. The smallest rate (FDA-recommended quantity) of organic Se supplementation
      was equally effective as supranutritional rates of Na-selenite supplementation in
      increasing WB-Se concentrations, demonstrating the greater oral bioavailability
      of organic Se.

PMID- 21965452
TI  - Effects of forage level in feedlot finishing diets on carcass characteristics and
      palatability of Jersey beef.
AB  - Jersey cattle are known for producing carcasses with a greater amount of
      marbling, but they require more days on feed to achieve acceptable market weights
      compared with other breeds. The objective of this study was to evaluate the
      effect of dietary forage (12 vs. 24% sudangrass:alfalfa hay, DM basis) in steam
      flaked, corn-based finishing diets on carcass characteristics, beef palatability,
      and retail color stability of steaks from Jersey beef compared with
      conventionally fed commodity beef strip loins (COM) of identified quality
      (Choice(-) and Select(+)). Jersey steers (n = 77) were blocked by BW and randomly
      assigned to 1 of the following treatments for a 383-d trial period: Jersey low
      12% (JL; n = 38) or Jersey high 24% (JH; n = 39) forage (DM basis). A comparison
      group was selected from conventionally fed cattle on the same day of slaughter as
      the Jersey treatments, and strip loins from USDA Select(+) (COM; n = 20) and
      Choice(-) (COM; n = 20) were removed for data analysis. Seventy-two hours
      postmortem, strip loins were removed, vacuum-packaged, and aged at 3 degrees C
      for 18 d postmortem. After the aging period, steaks from the LM were sliced,
      vacuum-packaged, and frozen (-20 degrees C) until analyzed. Jersey steaks had
      reduced (P < 0.05) Warner-Bratzler shear force values compared with COM steaks.
      Trained sensory panelists rated JL greater (P < 0.05) for initial and sustained
      tenderness and initial juiciness than COM, whereas JH was intermediate. As
      expected, marbling was greater (P < 0.05) for both JL and JH compared with COM,
      and trained sensory panel sustained juiciness, beef flavor intensity, and overall
      acceptability scores were greater (P < 0.05) for both JL and JH compared with
      COM; however, no differences (P = 0.14) were reported for consumer tenderness and
      flavor. Objective color (L*, a*, b*) measurements decreased (P < 0.05) over time
      across treatments. There were no differences among treatments for lightness (L*);
      however, overall during retail display JL were less (P < 0.05) red (a*) and
      yellow (b*) than JH and COM. Subjective color scores indicated both JL and JH
      were less red (P < 0.05) than COM. Steaks from Jersey were equal to and on some
      measurements more desirable than steaks from COM carcasses for both color
      stability and palatability. These results suggest that dietary forage level had
      minimal effects on carcass characteristics and beef palatability. However,
      feeding a low-forage diet decreases input cost and potentially results in a
      greater valued carcass. Finishing long-fed (383 d) Jersey steers can meet beef
      industry expectations with respect to quality grade.

PMID- 21965453
TI  - Inactivation at various temperatures of bovine viral diarrhea virus in beef
      derived from persistently infected cattle.
AB  - Bovine viral diarrhea virus (BVDV) is a pestivirus that is enzootic in most
      cattle populations throughout the world. This virus is present throughout the
      body of persistently infected (PI) cattle. Previous research has not assessed the
      cooking temperature at which BVDV in meat from PI cattle can be inactivated.
      Therefore, muscle tissue from 6 PI cattle was harvested, refrigerated, frozen,
      and heated to various internal temperatures. The concentration of virus present
      was determined by virus isolation. Average cell culture infective doses (50%
      endpoint; CCID(50)) of BVDV per gram of frozen, uncooked meat from PI cattle were
      10(5.85) CCID(50)/g of whole cuts and 10(6.02) CCID(50)/g of ground meat. The
      virus in whole and ground meat was consistently inactivated when cooked to
      temperatures greater than or equal to 75 degrees C. A second objective of this
      research was to thoroughly reassess if Vero cells were permissive to BVDV
      infection in our laboratory to provide further indication of whether primates,
      including humans, might be susceptible to BVDV. Vero cells were not permissive to
      infection with any of 43 different strains of BVDV that readily replicated in
      Madin Darby bovine kidney cells. In conclusion, this bovine pathogen, which is
      not considered to be a human pathogen, can be inactivated by cooking ground or
      whole cuts of meat to 75 degrees C or higher. Care should be taken to ensure that
      susceptible hosts such as pigs are not fed improperly cooked meat, meat by
      products, or waste food originating from PI cattle.

PMID- 21965454
TI  - Effect of oral meloxicam on health and performance of beef steers relative to
      bulls castrated on arrival at the feedlot.
AB  - Castration in weaned calves is stressful and affects profitability by reducing
      ADG and increasing susceptibility to disease. This study evaluated the effect of
      meloxicam, a nonsteroidal anti-inflammatory drug (NSAID), on performance and
      health of calves received as steers compared with bull calves surgically
      castrated on arrival at the feedlot. British * Continental bulls (n = 145) and
      steers (n = 113; BW = 193 to 285 kg) were transported for 12 h in 3 truckloads (d
      0), weighed, and randomly assigned to receive either lactose placebo (CONT; 1
      mg/kg) or meloxicam (MEL; 1 mg/kg) suspended in water and administered per os, 24
      h before castration. On d 1, bulls were surgically castrated (CAST) and steers
      were processed without castration (STR). Combinations of CONT/MEL and CAST/STR
      were allocated to 24 pens (6 pens per treatment) of 8 to 14 calves each. Pen was
      the experimental unit. Plasma meloxicam concentrations at the time of castration
      (d 1) were determined by HPLC-mass spectroscopy. Pen-level ADG, DMI, and G:F were
      estimated using BW obtained on d 0, 14, and 28 and weigh-back of feed. Individual
      animals were classified as sick based on a depression score of >=2 on a 5-point
      scale and a rectal temperature of >=39.8 degrees C. On d 0, 1, and 14, calf chute
      temperament was evaluated using a 4-point scale. Data were analyzed using
      generalized linear mixed models and survival curve analyses. Castration reduced
      pen ADG (P < 0.001) and G:F (P < 0.001) from d 1 to 14, yet no effects (P > 0.45)
      were apparent by d 28. For all treatment groups, DMI increased with days on feed
      (P < 0.0001) but was less in CAST compared with STR calves (P < 0.016) throughout
      the study. From d 15 to 28, ADG increased (P = 0.0011) in CAST but not STR
      calves, and G:F decreased (P = 0.0004) in STR but not CAST calves. In CAST calves
      only, MEL treatment reduced the pen-level first pull rate (P = 0.04) and reduced
      bovine respiratory disease morbidity rate (P = 0.03). The frequency of chute
      escape behavior was greater on arrival and at castration in CAST vs. STR calves
      (P < 0.01) but not significantly different at d 14 (P = 0.22). Mean MEL
      concentrations at castration were no different between treated STR and CAST
      calves (P = 0.70). Meloxicam administration before castration in postweaning
      calves reduced the incidence of respiratory disease at the feedlot. These
      findings have implications for developing NSAID protocols for use in calves at
      castration with respect to addressing animal health and welfare concerns.

PMID- 21965455
TI  - Effect of muscle type, sire breed, and time of weaning on fatty acid composition
      of finishing steers.
AB  - Thirty-three steer calves were used to determine the effect of sire breed (Angus
      or Charolais), time of weaning [normal weaned at approximately 210 d of age (NW)
      or late weaned at approximately 300 d of age (LW)], and muscle type [LM and
      semitendinosus muscle (STN)] on fatty acid composition. The whole plot consisted
      of a 2 (sire breed) * 2 (time of weaning) treatment arrangement, and the subplot
      treatment was muscle type. Body weights were recorded at 28-d intervals to
      determine animal performance. Muscle biopsies were collected on d 127 and 128 of
      finishing. All calves were slaughtered on d 138, and carcass data were collected.
      Angus-sired steers had lighter initial BW (271 vs. 298 kg; P = 0.02), and LW
      steers were heavier (351 vs. 323 kg; P = 0.03) on d 28, but no other differences
      in BW were noted. Charolais-sired steers had larger LM area (P = 0.03), reduced
      yield grades (P = 0.01), less 12th-rib fat (P < 0.01), and less marbling (P <
      0.01) than Angus-sired steers. Carcass measures overall indicate Angus-sired
      steers were fatter. Hot carcass weight was heavier (348 vs. 324 kg; P = 0.04) in
      LW steers than NW steers. No other differences (P > 0.05) were observed for
      feedlot performance or carcass characteristics. Total lipids were extracted from
      muscle biopsies, derivatized to their methyl esters, and analyzed using gas
      chromatography. The LM had greater SFA (43.94 vs. 35.76%; P < 0.01) and decreased
      unsaturated fatty acids (UFA; 56.90 vs. 66.19%; P < 0.01) compared with the STN.
      Percent total MUFA was greater in STN than LM (51.05 vs. 41.98%; P < 0.01). Total
      SFA, UFA, and MUFA did not differ due to sire breed or time of weaning. Total
      PUFA differed (P = 0.04) due to a sire breed * time of weaning interaction but
      did not differ due to muscle type, with greater PUFA in NW Charolais than any
      other sire breed * time of weaning combination. Observed changes in percent MUFA
      may be a result of greater Delta(9)-desaturase activity. The calculated
      desaturase index suggests STN has a greater Delta(9)-desaturase activity than LM,
      but no differences (P > 0.05) between sire breed or time of weaning were
      observed. These results indicate that sire breed, time of weaning, and muscle
      type all affect fatty acid composition in beef. This information provides insight
      into factors for manipulation of beef fatty acids. More research is needed to
      identify beef cuts based on fatty acid profile and healthfulness.

PMID- 21965456
TI  - Adaptive cell segmentation and tracking for volumetric confocal microscopy images
      of a developing plant meristem.
AB  - Automated segmentation and tracking of cells in actively developing tissues can
      provide high-throughput and quantitative spatiotemporal measurements of a range
      of cell behaviors; cell expansion and cell-division kinetics leading to a better
      understanding of the underlying dynamics of morphogenesis. Here, we have studied
      the problem of constructing cell lineages in time-lapse volumetric image stacks
      obtained using Confocal Laser Scanning Microscopy (CLSM). The novel contribution
      of the work lies in its ability to segment and track cells in densely packed
      tissue, the shoot apical meristem (SAM), through the use of a close-loop,
      adaptive segmentation, and tracking approach. The tracking output acts as an
      indicator of the quality of segmentation and, in turn, the segmentation can be
      improved to obtain better tracking results. We construct an optimization function
      that minimizes the segmentation error, which is, in turn, estimated from the
      tracking results. This adaptive approach significantly improves both tracking and
      segmentation when compared to an open loop framework in which segmentation and
      tracking modules operate separately.

PMID- 21965457
TI  - Bloodstream infections associated with parenteral nutrition preparation methods
      in the United States: a retrospective, large database analysis.

PMID- 21965458
TI  - Parenteral nutrition-induced hypersensitivity in an adolescent.
AB  - A case report of a 15-year-old adolescent male who developed a hypersensitivity
      reaction to a parenteral nutrition (PN) solution containing multivitamins (MVI)
      is presented. Within 30 minutes after initiation of PN and lipids, the patient
      developed a total-body pruritic urticarial rash that resolved after
      discontinuation of the infusions and administration of diphenhydramine.
      Rechallenge with the same PN solution excluding heparin, as well as lipids,
      resulted in a similar urticarial reaction that also resolved within 30 minutes
      after discontinuation of the infusions and administration of diphenhydramine.
      Another rechallenge with a solution containing dextrose and amino acids at the
      same concentrations contained in the original PN solution did not elicit an
      allergic reaction, whereas addition of MVI to the dextrose and amino acids
      resulted in a similar allergic reaction 20 minutes after the start of the
      infusion. It was determined that the MVI component of the PN was the most likely
      causative agent of this patient's urticarial reaction.

PMID- 21965459
TI  - Effect of early compared with delayed enteral nutrition on endocrine function in
      patients with traumatic brain injury: an open-labeled randomized trial.
AB  - BACKGROUND: Traumatic brain injury (TBI) results in a hypermetabolic and
      hypercatabolic status in which adequate nutrition support is essential to improve
      clinical outcome. The endocrine system of a patient with TBI is also affected and
      may play a critical role in either the metabolic or the immunologic response to
      the trauma. In the present study, the effect of standard, delayed enteral feeding
      (DEF), compared with early (within 24-48 hours) enteral feeding (EEF), on the
      endocrine function of patients with TBI was investigated. METHODS: This
      comparative, prospective, open-labeled, randomized study included TBI patients
      admitted to the intensive care unit (ICU). Injury severity was assessed by the
      Glasgow Coma Scale and predicted mortality by the Acute Physiology and Chronic
      Health Evaluation II. Twenty-five patients received DEF and 34 patients received
      EEF. The effect of the onset of nutrition on pituitary, thyroidal, gonadal, and
      adrenal function was investigated on days 6 and 12 after admission to the
      hospital. RESULTS: Levels of thyroid-stimulating hormone, free triiodothyronine,
      free thyroxine, and testosterone (in males) of DEF patients declined in
      comparison to levels of the day of admission to the ICU. The decrease of hormonal
      values was less pronounced in the EEF group. Cortisol concentrations rose in the
      DEF group; a lesser hormonal change was found in the EEF group. Deaths during the
      study for the DEF group and EEF group were 2 and 3, respectively. CONCLUSIONS:
      EEF may exert beneficial effects on the hormonal profile of TBI patients,
      possibly contributing to a better clinical outcome in this patient group.

PMID- 21965460
TI  - Correlation between nutrition assessment data and percent body fat via
      plethysmography in pediatric oncology patients.
AB  - BACKGROUND: Routine nutrition assessment is a core part of the nutrition
      management of the pediatric oncology population. The aims of this study were to
      build on the findings of a previous study to investigate the relationship between
      nutrition assessment variables and percent body fat (%BF) and to produce an
      equation to predict %BF in the pediatric oncology population. METHODS: The
      nutrition status assessment criteria for comparison with %BF measures were
      adapted with permission from the St Jude Children's Research Hospital nutrition
      screening system, Department of Clinical Nutrition. Additional measures not part
      of the screening system included midarm circumference (MAC); triceps, biceps,
      suprailiac, and subscapular skinfolds; and arm fat area. %BF was determined via
      air displacement plethysmography and interpreted via percentiles derived from
      body fat reference curves for healthy children. RESULTS: Forty-two children, 22
      males and 20 females, participated in the study. Correlational analysis revealed
      significant correlations with %BF and weight and body mass index z scores,
      percentage of ideal body weight (%IBW), MAC, skinfolds, arm fat area, and the
      total nutrition screening score. No relationship was found between height z
      score, percentage of weight loss over the previous 1 month, serum albumin,
      diagnosis risk, oral intake, and impending therapy or treatment side effects.
      Regression analysis found %BF = (1.4 * Biceps Skinfolds (mm) + (0.16 * %IBW) - 1
      to have the strongest correlation (r(2) = 0.74). CONCLUSIONS: The equation
      presented here requires validation to estimate %BF in the pediatric oncology
      population.

PMID- 21965461
TI  - The new ISSMIC database on in vivo micronucleus and its role in assessing
      genotoxicity testing strategies.
AB  - This paper presents a new curated database on in vivo micronucleus mutagenicity
      results, called ISSMIC. It is freely available at:
      http://www.iss.it/ampp/dati/cont.php?id=233&lang=1&tipo=7. The experimental
      results were critically reviewed, and evidence on target cell exposure was
      considered as well. The inspection of ISSMIC demonstrates that a large proportion
      of reported negative results in the literature (231 out 566 ISSMIC chemicals)
      lack a clear-cut, direct demonstration of toxicity at the target cells. Using
      this updated database, the predictive value of a compilation of Structural Alerts
      (SA) for in vivo micronucleus recently implemented in the expert system Toxtree
      was investigated. Individually, most of the SA showed a high Positive
      Predictivity (~80%), but the need for further expanding the list of alerts was
      pointed out as well. The role of in vivo micronucleus in strategies for
      carcinogenicity prediction was re-evaluated. In agreement with previous analyses,
      the data point to a low overall correlation with carcinogenicity. In addition,
      given the cost in animal lives and the time required for the experimentation, in
      many programs, the in vivo tests are used only to assess in vitro positive
      results. The ability of in vivo micronucleus to identify real positives (i.e.
      carcinogens) among chemicals positive in Salmonella or among chemicals inducing
      in vitro chromosomal aberrations was studied. It appears that the in vivo
      micronucleus test does not have added value and rather impairs the prediction
      ability of the in vitro tests alone. The overall evidence indicates that in vivo
      micronucleus--in its present form--cannot be considered an useful tool for
      routine genotoxicity testing but should be used in targeted mechanistic studies.

PMID- 21965462
TI  - Solid versus liquid particle sampling efficiency of three personal aerosol
      samplers when facing the wind.
AB  - The objective of this study was to examine the facing-the-wind sampling
      efficiency of three personal aerosol samplers as a function of particle phase
      (solid versus liquid). Samplers examined were the IOM, Button, and a prototype
      personal high-flow inhalable sampler head (PHISH). The prototype PHISH was
      designed to interface with the 37-mm closed-face cassette and provide an
      inhalable sample at 10 l min(-1) of flow. Increased flow rate increases the
      amount of mass collected during a typical work shift and helps to ensure that
      limits of detection are met, particularly for well-controlled but highly toxic
      species. Two PHISH prototypes were tested: one with a screened inlet and one with
      a single-pore open-face inlet. Personal aerosol samplers were tested on a bluff
      body disc that was rotated along the facing-the-wind axis to reduce
      spatiotemporal variability associated with sampling supermicron aerosol in low
      velocity wind tunnels. When compared to published data for facing-wind aspiration
      efficiency for a mouth-breathing mannequin, the IOM oversampled relative to
      mannequin facing-the-wind aspiration efficiency for all sizes and particle types
      (solid and liquid). The sampling efficiency of the Button sampler was closer to
      the mannequin facing-the-wind aspiration efficiency than the IOM for solid
      particles, but the screened inlet removed most liquid particles, resulting in a
      large underestimation compared to the mannequin facing-the-wind aspiration
      efficiency. The open-face PHISH results showed overestimation for solid particles
      and underestimation for liquid particles when compared to the mannequin facing
      the-wind aspiration efficiency. Substantial (and statistically significant)
      differences in sampling efficiency were observed between liquid and solid
      particles, particularly for the Button and screened-PHISH, with a majority of
      aerosol mass depositing on the screened inlets of these samplers. Our results
      suggest that large droplets have low penetration efficiencies through screened
      inlets and that particle bounce, for solid particles, is an important determinant
      of aspiration and sampling efficiencies for samplers with screened inlets.

PMID- 21965463
TI  - Does daily exposure to whole-body vibration and mechanical shock relate to the
      prevalence of low back and neck pain in a rural workforce?
AB  - OBJECTIVES: To determine whether whole-body vibration (WBV) and mechanical shock
      exposure from quad bike use are associated with the prevalence of neck and low
      back pain (LBP) in New Zealand farmers and rural workers. METHODS: Full-day WBV
      and mechanical shock exposures were gathered from 130 farmers and rural workers.
      Participants were surveyed for a history of neck or LBP in the past 7 days and in
      the past 12 months. Anthropometric, personal, and workplace data were also
      gathered. RESULTS: Physical exposures (mechanical shocks), employee status, and
      low levels of workplace satisfaction are all significantly associated with the 12
      month prevalence of LBP in this rural workforce that regularly use quad bikes.
      Both vibration and mechanical shock exposure were strongly associated with 12
      month prevalence of neck pain. The 7-day prevalence of neck pain showed a non
      significant association with mechanical shock and vibration. CONCLUSIONS:
      Knowledge of these findings will be valuable information for those who teach and
      advise on safe driving techniques for such vehicles in the rural workplace where
      reduction of physical exposures and injury rates is of high importance.

PMID- 21965464
TI  - Exposure and emissions monitoring during carbon nanofiber production--Part I:
      elemental carbon and iron-soot aerosols.
AB  - Production of carbon nanofibers and nanotubes (CNFs/CNTs) and their composite
      products is increasing globally. High volume production may increase the exposure
      risks for workers who handle these materials. Though health effects data for
      CNFs/CNTs are limited, some studies raise serious health concerns. Given the
      uncertainty about their potential hazards, there is an immediate need for
      toxicity data and field studies to assess exposure to CNFs/CNTs. An extensive
      study was conducted at a facility that manufactures and processes CNFs. Filter,
      sorbent, cascade impactor, bulk, and microscopy samples, combined with direct
      reading instruments, provided complementary information on air contaminants.
      Samples were analyzed for organic carbon (OC) and elemental carbon (EC), metals,
      and polycyclic aromatic hydrocarbons (PAHs), with EC as a measure of CNFs.
      Transmission electron microscopy with energy-dispersive X-ray spectroscopy also
      was applied. Fine/ultrafine iron-rich soot, PAHs, and carbon monoxide were
      production byproducts. Direct-reading instrument results were reported previously
      [Evans DE et al. (Aerosol monitoring during carbon nanofiber production: mobile
      direct-reading sampling. Ann Occup Hyg 2010;54:514-31.)] Results for time
      integrated samples are reported as companion papers in this Issue. OC and EC,
      metals, and microscopy results are reported here, in Part I, while results for
      PAHs are reported in Part II [Birch ME. (Exposure and Emissions Monitoring during
      Carbon Nanofiber Production-Part II: Polycyclic Aromatic Hydrocarbons. Ann.
      Occup. Hyg 2011; 55: 1037-47.)]. Respirable EC area concentrations inside the
      facility were about 6-68 times higher than outdoors, while personal breathing
      zone samples were up to 170 times higher.

PMID- 21965465
TI  - Asbestos-related diseases in automobile mechanics.
AB  - PURPOSE: Automobile mechanics have been exposed to asbestos in the past, mainly
      due to the presence of chrysotile asbestos in brakes and clutches. Despite the
      large number of automobile mechanics, little is known about the non-malignant
      respiratory diseases observed in this population. The aim of this retrospective
      multicenter study was to analyse the frequency of pleural and parenchymal
      abnormalities on high-resolution computed tomography (HRCT) in a population of
      automobile mechanics. METHODS: The study population consisted of 103 automobile
      mechanics with no other source of occupational exposure to asbestos, referred to
      three occupational health departments in the Paris area for systematic screening
      of asbestos-related diseases. All subjects were examined by HRCT and all images
      were reviewed separately by two independent readers; who in the case of
      disagreement discussed until they reached agreement. Multiple logistic regression
      models were constructed to investigate factors associated with pleural plaques.
      RESULTS: Pleural plaques were observed in five cases (4.9%) and interstitial
      abnormalities consistent with asbestosis were observed in one case. After
      adjustment for age, smoking status, and a history of non-asbestos-related
      respiratory diseases, multiple logistic regression models showed a significant
      association between the duration of exposure to asbestos and pleural plaques.
      CONCLUSIONS: The asbestos exposure experienced by automobile mechanics may lead
      to pleural plaques. The low prevalence of non-malignant asbestos-related
      diseases, using a very sensitive diagnostic tool, is in favor of a low cumulative
      exposure to asbestos in this population of workers.

PMID- 21965466
TI  - A large-scale evaluation of Risk Matrix 2000 in Scotland.
AB  - Risk Matrix 2000 is a statistically derived risk-assessment instrument for use
      with convicted male sex offenders. It is a core element of the sex offender risk
      assessments carried out in England, Wales, and Scotland. This study examines its
      validity in a large cohort of sex offenders released from Scottish prisons. It
      compares 5-year outcomes with findings from the original Risk Matrix validity
      sample (a 1979 cohort of sex offenders in England and Wales). The instrument had
      moderate predictive validity and performed in a similar manner in the two studies
      in spite of different underlying base rates of reconviction.

PMID- 21965467
TI  - Offender types and criminality dimensions in male juveniles convicted of sexual
      offenses.
AB  - Previous studies have described juveniles who sexually offended (JSO) as a rather
      heterogeneous population. In consequence, different typologies of JSO have been
      proposed for a better understanding of the causes and interventional needs of
      JSO. Three previously described types have received support in previous studies,
      namely, the victim age type (JSO offending against children vs. adolescents or
      adults), the co-offender status type (JSO offending as singles vs. in groups),
      and the crime history type (JSO with vs. without a previous history of crime).
      The validity of these types is tested in a consecutive sample of 223 criminal
      male adolescents, who had been convicted of a sexual offense between 2000 and
      2008 in the Canton of Zurich (Switzerland). By analyzing nine offender
      characteristics, four victim characteristics and six offense characteristics, the
      best evidence is found for the victim age-based type. The co-offender status and
      the crime history types are less well supported. However, all three types are
      related to each other and do not provide a comprehensive characterization of JSO.
      Therefore, an additional principal component analyses is performed searching for
      basic dimensions of juvenile sexual delinquency and leading to the following
      factors: "single offender with severe molestation of a related child,"
      "persistent general delinquent with migrant background," "older offender with
      alcohol use and familial constraints," "multiple and aggressive offender with
      social adversities," and "offender with unselected and multiple victims." These
      five dimensions reflect different relevant factors of sexual offending behavior
      in male juveniles and may have further impact on forensic and clinical practice.

PMID- 21965468
TI  - Brain mapping biomarkers of socio-emotional processing in schizophrenia.
AB  - The Cognitive Neuroscience Treatment Research to Improve Cognition in
      Schizophrenia (CNTRICS) initiative has formed with the expressed intent of
      identifying constructs and paradigms that would identify biomarkers of psychosis.
      The manipulation of these biomarkers would serve as targets for treatment
      interventions. The second phase of CNTRICS consisted of critical discussions
      evaluating brain mapping (functional neuroimaging and brain electrical activity)
      paradigms as biomarkers to measure specific constructs. Among the constructs
      identified in, CNTRICS I was socio-emotional processing, specifically focused on
      affect recognition. Here, we provide a critical appraisal of the ability of
      candidate socio-emotional tasks to identify putative biomarkers and
      recommendations for future directions in this rapidly moving research domain.

PMID- 21965469
TI  - Is the acute NMDA receptor hypofunction a valid model of schizophrenia?
AB  - Several genetic, neurodevelopmental, and pharmacological animal models of
      schizophrenia have been established. This short review examines the validity of
      one of the most used pharmacological model of the illness, ie, the acute
      administration of N-methyl-D-aspartate (NMDA) receptor antagonists in rodents. In
      some cases, data on chronic or prenatal NMDA receptor antagonist exposure have
      been introduced for comparison. The face validity of acute NMDA receptor blockade
      is granted inasmuch as hyperlocomotion and stereotypies induced by phencyclidine,
      ketamine, and MK-801 are regarded as a surrogate for the positive symptoms of
      schizophrenia. In addition, the loss of parvalbumin-containing cells (which is
      one of the most compelling finding in postmortem schizophrenia brain) following
      NMDA receptor blockade adds construct validity to this model. However, the lack
      of changes in glutamic acid decarboxylase (GAD(67)) is at variance with human
      studies. It is possible that changes in GAD(67) are more reflective of the
      neurodevelopmental condition of schizophrenia. Finally, the model also has
      predictive validity, in that its behavioral and transmitter activation in rodents
      are responsive to antipsychotic treatment. Overall, although not devoid of
      drawbacks, the acute administration of NMDA receptor antagonists can be
      considered as a good model of schizophrenia bearing a satisfactory degree of
      validity.

PMID- 21965470
TI  - Is the recall of men who have sex with men (MSM) diagnosed as having bacterial
      sexually transmitted infections (STIs) for re-screening a feasible and effective
      strategy?
AB  - OBJECTIVES: To assess the feasibility and outcomes of recalling men who have sex
      with men (MSM) diagnosed as having a bacterial sexually transmitted infection
      (STI) for re-screening. METHODS: This evaluation was conducted from December 2008
      for a 9-month period. MSM diagnosed as having a bacterial STI in that period were
      offered recall for re-screening 3 months after their diagnosis. Re-screening
      rates and infection incidence were calculated. Differences in baseline
      characteristics by re-screening status and factors predictive of infection at re
      screening were assessed using the Mann-Whitney test, chi(2) test and logistic
      regression. RESULTS: Of the 337 MSM diagnosed as having a bacterial STI, 301 were
      offered recall. Of these, 206 (68.4%) re-screened after 3 months, 30 (10%)
      declined and the remainder did not re-attend despite giving verbal consent.
      Compared with those not re-screening, those re-screening were less likely to be
      HIV positive (p=0.001), but there was no difference in baseline risk behaviours.
      There were 15 diagnoses of bacterial STIs at re-screening (29 per 100 person-year
      follow-up (pyfu); 95% CI 14.3 to 43.7) and five new HIV diagnoses of whom three
      had a negative test at baseline, one tested negative 6 months earlier and one
      never tested. Among those testing at both time points, the HIV incidence was 8.3
      per 100 pyfu (95% CI 0.0 to 17.7). CONCLUSIONS: This evaluation demonstrates a
      'recall for re-screening' strategy is feasible in terms of high re-screening
      rates and incidence of new infections diagnosed. Experimental evidence is needed
      to assess cost-effectiveness and whether it achieves its aim of reducing
      transmission of STIs and HIV.

PMID- 21965472
TI  - Clinical relevance of flow cytometric immunophenotyping of the cerebrospinal
      fluid in patients with diffuse large B-cell lymphoma.
AB  - BACKGROUND: Central nervous system (CNS) relapse is an uncommon but dramatic
      complication of diffuse large B-cell lymphoma (DLBCL). Several studies have
      demonstrated the superiority of cerebrospinal fluid (CSF) flow cytometry (FCM),
      as compared with conventional cytology (CC), in detecting occult leptomeningeal
      disease. The clinical relevance of a positive FCM still has to be clarified.
      PATIENTS AND METHODS: We analyzed CSF from 114 DLBCL patients at diagnosis (n =
      95) or at relapse (n = 19) by FCM and CC. Most patients received meningeal
      prophylaxis. FCM results did not influence treatment strategies. RESULTS:
      Fourteen samples were FCM+, versus one CC+ (also FCM+). Within all patients
      without neurological symptoms (n = 101), four (4%) relapsed in the CNS, with a
      median time to relapse of 5.2 months. Only one-fourth (25%) was FCM+ before
      relapse. More than one extranodal disease site and elevated lactate dehydrogenase
      levels were associated with an increased risk of CNS relapse. CONCLUSIONS: FCM
      gives far more positive results than CC. However, a positive FCM result did not
      translate into a significant increase in CNS relapse rate in this histologically
      uniform population receiving CNS prophylaxis.

PMID- 21965471
TI  - Prognostic importance of DNA ploidy and DNA index in stage I and II endometrioid
      adenocarcinoma of the endometrium.
AB  - BACKGROUND: We evaluated the prognostic importance of DNA ploidy in stage I and
      II endometrioid adenocarcinoma (EAC) of the endometrium with a focus on DNA
      index. PATIENTS AND METHODS: High-resolution DNA ploidy analysis was carried out
      in tumor material from 937 consecutive patients with International Federation of
      Gynecology and Obstetrics (FIGO) stage I and II EAC of the endometrium. RESULTS:
      Patients with diploid (N = 728), aneuploid tumor with DNA index <= 1.20 (N =
      118), aneuploid tumors with DNA index >1.20 (N = 39) and tetraploid tumor (N =
      52) had 5-year recurrence rates 8%, 14%, 20% and 12%, respectively. Patients with
      aneuploid tumor with DNA index >1.20 had a poorer 5-year progression-free
      survival (67%) and overall survival (72%) compared with the patients with
      aneuploid tumor with DNA index <= 1.20 (81% and 89%, respectively). Aneuploid
      tumors with DNA index <= 1.20 relapsed mainly in the vagina and pelvis, whereas
      aneuploid tumors with DNA index >1.20 relapsed predominantly outside pelvis.
      CONCLUSIONS: The recurrence risk for the patients with aneuploid tumor is higher
      than the patients with diploid tumor in EAC of the endometrium. Based on DNA
      index with cut-off 1.20, aneuploid tumors can be separated into two subgroups
      with different recurrence pattern and survival.

PMID- 21965473
TI  - Circulating tumor cells in immunohistochemical subtypes of metastatic breast
      cancer: lack of prediction in HER2-positive disease treated with targeted
      therapy.
AB  - BACKGROUND: Circulating tumor cells (CTCs) are associated with inferior prognosis
      in metastatic breast cancer (MBC). We hypothesized that the relationship between
      CTCs and disease subtype would provide a better understanding of the clinical and
      biologic behavior of MBC. PATIENTS AND METHODS: We retrospectively analyzed 517
      MBC patients treated at a single institution. Subtypes of primary tumors were
      analyzed by immunohistochemical (IHC) or fluorescent in situ hybridization
      analyses and CTCs were enumerated by CellSearch((r)) at starting a new therapy.
      Overall survival (OS) and progression-free survival durations for each IHC
      subtype were determined. RESULTS: At a median follow-up of 24.6 months, 276 of
      517 (53%) patients had died. The median OS for patients with <5 and >= 5 CTCs
      were 32.4 and 18.3 months, respectively (P < 0.001). Except in HER2+ patients,
      the prognostic value of CTCs was independent of disease subtype and disease site.
      CONCLUSIONS: In this large retrospective study, CTCs were strongly predictive of
      survival in all MBC subtypes except HER2+ patients who had been treated with
      targeted therapy. Our results clearly demonstrate the value of enumerating CTCs
      in MBC and strongly suggest an interesting biological implication in the HER2+
      subset of patients that need to be further explored.

PMID- 21965474
TI  - Changes in incidence, survival and mortality of prostate cancer in Europe and the
      United States in the PSA era: additional diagnoses and avoided deaths.
AB  - BACKGROUND: We describe changes in prostate cancer incidence, survival and
      mortality and the resulting impact in additional diagnoses and avoided deaths in
      European areas and the United States. METHODS: Using data from 12 European cancer
      registries and the Surveillance, Epidemiology and End Results program, we
      describe changes in prostate cancer epidemiology between the beginning of the PSA
      era (USA: 1985-1989, Europe: 1990-1994) and 2002-2006 among patients aged 40-64,
      65-74, and 75+. Additionally, we examine changes in yearly numbers of diagnoses
      and deaths and variation in male life expectancy. RESULTS: Incidence and
      survival, particularly among patients aged <75, increased dramatically, yet both
      remain (with few exceptions in incidence) lower in Europe than in the United
      States. Mortality reductions, ongoing since the mid/late 1990 s, were more
      consistent in the United States, had a distressingly small absolute impact among
      patients aged 40-64 and the largest absolute impact among those aged 75+. Overall
      ratios of additional diagnoses/avoided deaths varied between 3.6 and 27.6,
      suggesting large differences in the actual impact of prostate cancer incidence
      and mortality changes. Ten years of remaining life expectancy was reached between
      68 and 76 years. CONCLUSION: Policies reflecting variation in population life
      expectancy, testing preferences, decision aids and guidelines for surveillance
      based management are urgently needed.

PMID- 21965476
TI  - Psychosocial factors associated with suicidal ideation among young men exempted
      from compulsory military or civil service.
AB  - AIMS: The aim of this study was to identify factors associated with suicidal
      ideation among young men exempted from compulsory military or civil service in
      Finland. METHODS: The study involved a total of 356 men exempted from military or
      civil service. The research data were collected using questionnaires and register
      data. RESULTS: One third of the young men exempted from compulsory military or
      civil service reported serious suicidal ideation. Of the men with serious
      suicidal ideation, one third had attempted suicide. Various childhood adversities
      and current stressful life events and problems were associated with suicidal
      ideation. Multivariate logistic regression analysis showed that the following
      factors were independently associated with suicidal ideation: maternal alcohol
      related problems, changes in the family, discord with the boss over the past 12
      months, and lack of social support. Accumulation of problems predicted suicidal
      ideation. CONCLUSIONS: Men exempted from compulsory military or civil service
      comprise an important target group in the prevention of suicide. In order to
      prevent suicidal behaviour among young men at risk, it is important to address
      the significance of social support and relationships, and likewise to be aware of
      early risk indicators such as maternal alcohol-related problems.

PMID- 21965475
TI  - A multicenter phase III prospective randomized trial of high-dose epirubicin in
      combination with cyclophosphamide (EC) versus docetaxel followed by EC in node
      positive breast cancer. GOIM (Gruppo Oncologico Italia Meridionale) 9902 study.
AB  - BACKGROUND: The Gruppo Oncologico Italia Meridionale 9902 trial compared four
      cycles of high-dose epirubicin plus cyclophosphamide (EC) with four cycles of
      docetaxel (Taxotere, D) followed by four cycles of EC as adjuvant treatment of
      node-positive breast cancer. PATIENTS AND METHODS: Patients were randomly
      assigned to EC (E 120 mg/m(2), C 600 mg/m(2), arm A) for four cycles or four
      cycles of D (100 mg/m(2)) followed by four cycles of EC (arm B), both regimens
      every 21 days. Hormone receptor-positive patients were given hormonal therapy for
      5 years. Primary end point was 5-year disease-free survival (DFS). Secondary
      objectives were overall survival (OS) and safety. RESULTS: There were 750
      patients enrolled. With a median follow-up of 64 months, 5-year DFS was 73.4% in
      both arms, and 5-year OS was 89.5% versus 90.7% in arm A and B [hazard ratio was
      0.99 (95% confidence interval for DFS 0.75-1.31; P = 0.95)], respectively. Grade
      3-4 toxicity was more common in arm B. CONCLUSIONS: This study did not show
      advantages from the addition of docetaxel to high-dose EC as adjuvant
      chemotherapy in node-positive breast cancer. The small sample size and low number
      of DFS events may have limited the ability to observe statistically significant
      difference between the two arms.

PMID- 21965477
TI  - Increasing prevalence of depression from 2000 to 2006.
AB  - AIM: Depression is the leading cause of disability and is projected to become the
      second highest burden of disease (measured in disability-adjusted life years) by
      2020, but only a few studies have examined changes over time in the occurrence of
      depression. The aim of this study is to provide evidence to the hypothesis that
      the prevalence of depression is rising in the Danish population. We will do that
      in a longitudinal design among adult Danes by studying the trends from 2000 to
      2006 of major depressive disorder (MDD) as well as the distribution across the
      whole Major Depression Inventory (MDI) scale. In addition, we will investigate
      whether the trend in MDD is similar across socioeconomic groups. METHODS: A
      random sample of 4759 Danes in their forties and fifties were followed in a
      longitudinal study based on postal questionnaires answered in 2000 and 2006.
      RESULTS: The prevalence of MDD increased from 2.0% to 4.9% during 2000-06. Also
      the distribution of the MDI score in its entirety moves higher up the scale, with
      the 90th percentile changing from 12 in year 2000 to 20 in 2006. The increasing
      prevalence is in absolute terms more pronounced among women in their forties and
      in lower socioeconomic positions. CONCLUSIONS: The rising MDI score indicates
      that MDD as well as mental health generally is of public health concern.

PMID- 21965478
TI  - Health, sleep, and professional career in female white-collar workers back to
      work after long-term sick-listing due to minor mental disorders.
AB  - AIMS: This study is a 3-year follow up of female white-collar workers, who were
      on long-term sick leave in 2004 due to stress-related and minor mental disorders.
      The aim is to show what promotes return-to-work (RTW) and the impact of a long
      period of sickness absence on professional career. METHODS: The study includes a
      cohort of 233 women who were currently on medically certified sick leave lasting
      >=90 days in 2004. A postal questionnaire was sent out after 34 months, regarding
      self-rated health, quality of sleep, sick-listing status, occupational status,
      etc. RESULTS: After 34 months, 69% of the women had fully returned to working
      life. One of the most salient findings is that almost half of those had changed
      jobs and more than a third were in a new profession. Those who were back in
      working life rated less negative consequences of the long-term sick-listing on
      their professional career and their quality of sleep was better (OR 2.90, 95% CI
      1.50-5.60 "sleeping all night"). Self-rated health did not show significant
      association with RTW (OR 2.83, 95% CI 0.91-8.77). Those who had returned to
      working life reported more control over their lives (OR 1.98, 95% CI 1.01-3.88).
      CONCLUSIONS: The findings imply that, in work health promotion and rehabilitation
      and efforts to prevent sickness absence due to stress-related disorders,
      important factors to be considered are job mobility, changes in present work,
      improved sleep, and control over one's own life.

PMID- 21965479
TI  - Why are general practitioners reluctant to enrol patients into a RCT on sick
      leave? A qualitative study.
AB  - AIMS: To explore the reluctance of, and examine the arguments given by Norwegian
      general practioners (GPs), regarding their unwillingness to recruit their
      patients for a study where sick leave would be based on randomization. METHODS: A
      qualitative study presenting individual arguments from 50 Norwegian GPs, as
      written responses to a web-based, open-ended questionnaire. The responses,
      ranging from 3-145 words, were analysed with systematic text condensation.
      RESULTS: The GPs did not want to participate in a study where sick leave was
      decided by randomization. First, the complexity of clinical judgment was
      addressed. Would it be ethically acceptable to set the professional and medical
      assessment aside, and if so, was there any better judge than the regular GP in
      making this important decision? Second, the arguments dealing with sick leave as
      a human and legal right were addressed. Will patients feel they have a legitimate
      right to sick leave and will they be open for discussion with their GP? Third,
      the risk of jeopardizing the relationship between patient and doctor was
      emphasized. Would the patients be able to trust their GP if he or she offered the
      patient entry into a trial where sick leave would be decided by randomization?
      CONCLUSIONS: Randomization of sick leave in general practice in Norway was not
      viewed as feasible by the GPs themselves because of the importance of clinical
      judgment, ethical obligations, and the belief that the patients would refuse
      participation, and thereby, that the doctor-patient relationship would be
      disturbed.

PMID- 21965480
TI  - High burden of musculoskeletal conditions: a problem that has only recently come
      to recognition.
AB  - OBJECTIVES: Musculoskeletal conditions have only recently been acknowledged and
      research on their burden is scarce in the Middle East and North African (MENA)
      region. For the first time, a population based study was conducted in Lebanon to
      assess the prevalence, level of disability, and health seeking behaviours related
      to musculoskeletal pain and rheumatic disorders. METHODS: A random sample of 500
      participants aged >= 15 years from Southern Lebanon was interviewed using the
      COPCORD (Community Oriented Program for Control of Rheumatic Diseases)
      questionnaire. RESULTS: The prevalence of current musculoskeletal pain was 31.2%
      [CI (27.0-35.2%)]. Being a female [OR=1.8, CI (1.2-2.8)] and of advancing age
      [OR=1.03, CI (1.01-1.05)] were the only significant factors associated with
      current musculoskeletal pain. Prevalence of current functional disability was
      6.4% [CI (4.2-8.5%)]. Around quarter (26.0%) [CI (22.3-30.1%)] of our sample
      sought some kind of treatment. The overall prevalence rate of rheumatic disease
      was 17.0% [CI (13.7-20.3%)]. DISCUSSION: Our findings indicate that
      musculoskeletal conditions are common in Lebanon. This is a timely public health
      issue that needs further investigation and solid recognition by health
      authorities. Community-based interventions should target patients to prompt them
      to seek early help in order to prevent the development of musculoskeletal pain
      into disorders.

PMID- 21965481
TI  - An exploratory study of young women adjusting to developmental dysplasia of the
      hip and deciding on treatment choices.
AB  - OBJECTIVE: To explore the experiences of young women adjusting to living with
      developmental dysplasia of the hip (DDH) and deciding on treatment choices.
      METHODS: Exploratory study of a set of online postings from one message board
      aimed at women with DDH. Postings of five, purposively selected users were
      explored from first posting to the time of their peri-acetabular osteotomy
      surgery. Data analysis was performed through the approach of interpretive
      phenomenological analysis. RESULTS: Two major concepts were prominent across
      participants' accounts; first, 'challenging the life course and identity as a
      young woman' and second, 'saving my joints'. Central was the women's description
      of how the diagnosis of DDH challenged the way they viewed themselves as young
      women. Once the women began to understand the long-term implications of having
      DDH they all began a quest to save their 'native joint', delaying the need for an
      artificial joint for as long as possible. CONCLUSION: The findings demonstrate
      the personal nature and diversity of the journeys the women followed. DDH
      potentially provides a critical case for exploration of the process of
      adjustment, as its treatment pathway and rehabilitation are lengthy and both
      physically and emotionally demanding.

PMID- 21965482
TI  - Defining professional success to define our profession.

PMID- 21965483
TI  - Team morale.

PMID- 21965484
TI  - Using emergency departments.

PMID- 21965485
TI  - Missed appointments.

PMID- 21965486
TI  - The effect of electronic health records on the use of clinical care guidelines
      for patients with medically complex conditions.
AB  - BACKGROUND: The emergence of health information technology provides an
      opportunity for health care providers to improve the quality and safety of dental
      care, particularly for patients with medically complex conditions. METHODS: The
      authors randomized each of 15 dental clinics (HealthPartners, Bloomington, Minn.)
      to one of three groups to evaluate the impact of two clinical decision support
      (CDS) approaches during an 18-month study period. In the first approach--provider
      activation through electronic dental records (EDRs)--a flashing alert was
      generated at the dental visit to identify patients with medically complex
      conditions and to direct the dental care provider to Web-based personalized care
      guidelines. In the second approach--patient activation through personal health
      records--a secure e-mail was generated or a letter was mailed to patients before
      dental visits encouraging them to ask their dental care provider to review the
      care guidelines specific to their medical conditions. RESULTS: The authors
      evaluated the rate of reviewing care guidelines among 102 providers. Participants
      in the provider and patient activation groups increased their use of the system
      during the first six months, which had a generalized effect of increasing use of
      the guidelines for all patients, even if they were not part of the study (P <
      .05). The study results showed that provider activation was more effective than
      was patient activation. However, providers did not sustain their high level of
      use of the system, and by the end of the study, the rate of use had returned to
      baseline levels despite participants' continued receipt of electronic alerts.
      CONCLUSIONS: The study results demonstrated that review of clinical care
      guidelines for patients with medically complex conditions can be improved with
      CDS systems that involve the use of electronic health records. CLINICAL
      IMPLICATIONS: As the U.S. population ages, dentists must be vigilant in adapting
      care for patients with medically complex conditions to ensure therapeutic safety
      and effectiveness. Expanded use of CDS via EDRs can help dental care providers
      achieve this objective.

PMID- 21965487
TI  - The validity and reliability of mixed-dentition analysis methods: a systematic
      review.
AB  - BACKGROUND: The authors conducted a literature review to determine the validity
      and reliability of mixed-dentition analysis (MDA) methods used to predict
      permanent tooth size in the mixed dentition and to evaluate the effect of
      relevant variables. TYPES OF STUDIES REVIEWED: The authors searched eight online
      databases for studies of MDA. They selected 39 articles. Inclusion criteria
      included assessment of mesiodistal tooth width predictions of canines and
      premolars, use of study-model measurements with or without radiographs,
      reliability and validity of MDA values and a minimum sample size of 10. RESULTS:
      All MDA methods had positively correlated validity and high intrarater
      reliability. Mean differences were less than 2 millimeters with correlation
      coefficients that tended to be above 0.6. Correlation coefficients were less
      variable with multiple linear regression equations (MLREs) than with simple
      linear regression equations (SLREs) with the study-model method, but the opposite
      was true with the radiographic method. Polymorphisms based on ethnicity, sex, jaw
      or side of mouth did not meaningfully influence the validity of SLRE predictions,
      but some differences were apparent with the use of MLRE predictions. CLINICAL
      IMPLICATIONS: The results of this review call into question the clinical
      implications of the multiple variations of MDA that have been described in the
      literature.

PMID- 21965488
TI  - Evaluation of the muscle relaxant cyclobenzaprine after third-molar extraction.
AB  - BACKGROUND: Pain, swelling and trismus are undesirable effects of extraction of
      impacted mandibular third molars. The authors conducted a study to evaluate the
      effectiveness of the muscle relaxant cyclobenzaprine when used as a supplement to
      cryotherapeutic, antibiotic and steroidal anti-inflammatory treatment with the
      aim of reducing undesirable consequences after third-molar extraction. METHODS:
      The authors conducted a prospective, randomized, double-masked, placebo
      controlled clinical trial involving 50 participants aged 18 to 29 years randomly
      assigned to receive cyclobenzaprine or the placebo. The authors used a split
      mouth design, so each participant acted as his or her own control. For each
      participant, the authors extracted one impacted mandibular third molar on each
      side of the mouth at different times. Participants received 10 milligrams of
      cyclobenzaprine or a placebo once per day the day before surgery, the day of
      surgery and the first day after surgery. The authors assessed the participants'
      postoperative pain by means of a visual analog scale at four, six, eight, 12, 24
      and 48 hours. They measured the participants' swelling and maximal interincisor
      distance at 48 hours and seven days. RESULTS: The authors assessed both sides of
      each participant's mouth for differences in pain, swelling and trismus. They
      found no statistically significant differences between sides of the mouth
      regarding these three variables. CONCLUSIONS: The results of this trial indicate
      that the influence of cyclobenzaprine over pain, swelling and trismus does not
      justify prescribing additional medication for patients undergoing third-molar
      extraction. CLINICAL IMPLICATIONS: The muscle relaxant cyclobenzaprine was
      ineffective in reducing pain, swelling and trismus after third-molar extraction.

PMID- 21965489
TI  - Dietary and nutritional needs of patients undergoing therapy for head and neck
      cancer.
AB  - BACKGROUND: Nutrient and caloric intake is critical during therapy for head and
      neck cancer. METHODS: The authors review the oral complications experienced by,
      and dietary and nutritional needs of, patients during therapy. They also present
      recommendations for oral care and calorie and nutrient intake. CONCLUSIONS: Oral
      health care professionals can assist patients during treatment for cancer in
      maintaining oral, systemic and nutritional health, as well as in controlling oral
      symptoms. Recovery from the acute toxicities of therapy often requires diet
      modification, tube feeding or both to meet patients' energy and nutrient demands.
      CLINICAL IMPLICATIONS: Effective management of oral complications of therapy for
      cancer is necessary to facilitate oral intake throughout treatment. Oral health
      care professionals should be part of the multidisciplinary team helping meet the
      needs of patients during treatment.

PMID- 21965490
TI  - A phase II trial of a transmucosal herbal patch for the treatment of gingivitis.
AB  - BACKGROUND: Systemic treatments for gingivitis frequently are inadequate for
      controlling specific sites of severe gingival inflammation. The authors conducted
      a study to test site-specific therapy using a transmucosal herbal periodontal
      patch (THPP) that was impregnated with plant extracts reported to reduce
      inflammatory response. METHODS: The study was a single-center, randomized,
      placebo-controlled, double-masked, longitudinal phase II trial involving
      participants with clinically diagnosed gingivitis. Participants who were enrolled
      in the study received either THPPs or placebo patches (PP) for three days. The
      authors evaluated gingival inflammation visually using the gingival index (GI)
      and by measuring gingival crevicular fluid beta-glucuronidase (BG) enzymatic
      activity at baseline (day one) and on days two, four, eight and 15. RESULTS: The
      authors randomly assigned 53 participants to receive the THPP or the PP.
      Participants who received the THPPs had a greater reduction in mean GI scores
      than did those who received the PPs. This finding was significant on days four
      and 15. The percentage of participants whose GI scores decreased by one or more
      was higher among those receiving the THPP than among those receiving the PP, as
      assessed on days four and 15. The average decrease in BG levels (fluorescence
      units) for participants receiving the THPP was significantly greater on days four
      and eight than they were for those receiving the PP. No serious adverse events
      were associated with the use of the THPP. CONCLUSIONS: Topical treatment by means
      of the THPP may be effective and safe in reducing topical gingival inflammation.
      Further studies are needed to confirm these findings and determine the best
      method for administering the THPP and the appropriate dosing. CLINICAL
      IMPLICATIONS: Site-specific treatment of gingival inflammation is feasible and
      could be used as an adjunct for systemic therapeutic interventions.

PMID- 21965491
TI  - Cuspal deflection and depth of cure in resin-based composite restorations filled
      by using bulk, incremental and transtooth-illumination techniques.
AB  - BACKGROUND: Restoration techniques affect shrinkage stress and depth of cure. The
      authors tested cuspal deflection and depth of cure resulting from the use of
      different techniques (bulk, incremental, bulk/transtooth illumination) and two
      resin-based composites (deep curing and conventional). METHODS: The authors
      restored extracted teeth with deep-curing X-tra fil (VOCO, Cuxhaven, Germany) (by
      using bulk and incremental techniques) and Filtek Supreme Plus (3M ESPE, St.
      Paul, Minn.) (by using bulk, incremental and bulk/transtooth-illumination
      techniques). The sample size for each technique was five. They determined cuspal
      deflections as changes in buccal and lingual surfaces before and after
      restoration. To determine the extent of cure, they measured hardness 0.5 to 3.5
      millimeters deep on the sectioned restorations. RESULTS: The authors found no
      difference in cuspal deflection between filling techniques within the same
      materials (P > .05). They found no difference in hardness for X-tra fil at any
      depth with either the bulk or the incremental technique (P > .05). Filtek Supreme
      Plus had higher hardness values at depths of less than 1.5 mm with the
      bulk/transtooth-illumination technique, whereas the bulk technique resulted in
      lower hardness values at depths of 2.0 mm and below (P < .05). CONCLUSIONS:
      Cuspal deflection was not affected by filling techniques. X-tra fil cured up to a
      depth of at least 3.5 mm; Filtek Supreme Plus had lower curing values below a
      depth of 2 mm. The transtooth-illumination technique improved curing depth for
      restorations placed in bulk. CLINICAL IMPLICATIONS: When using resin-based
      composite restorative materials, clinicians should be more concerned about the
      effect of filling techniques on curing depth than about how these techniques
      affect shrinkage stresses.

PMID- 21965492
TI  - Development of a brief and effective temporomandibular disorder pain screening
      questionnaire: reliability and validity.
AB  - BACKGROUND: Available screening instruments for identifying temporomandibular
      disorders (TMDs) exhibit methodological or logistic limitations. The authors
      conducted a study to develop and assess the validity of a self-report instrument
      in screening patients for pain-related TMDs. METHODS: By using psychometric
      methods for item selection, the authors developed short (three-item) and long
      (six-item) versions of the questionnaire and evaluated them for validity among
      504 participants. RESULTS: Internal reliability was excellent, with coefficient
      alpha values of 0.87 and 0.93 for the short and long versions, respectively. When
      the authors dichotomized instrument scores at optimal thresholds, both versions
      had a sensitivity of 99 percent and a specificity of 97 percent for correct
      classification of the presence or absence of TMD. The specificity was at least 95
      percent in the correct identification of people with nonpainful TMJ disorders or
      headahce without TMD pain. CONCLUSIONS: With use of appropriate psychometric
      methodology, the selected items exhibited excellent content validity. The
      excellent levels of reliability, sensitivity and specificity demonstrate the
      validity and usefulness of this instrument. CLINICAL IMPLICATIONS: Using this
      instrument will allow clinicians to identify more readily-and cost-effectively
      most patients with painful TMD conditions for whom early and reliable
      identification would have a significant effect on diagnosis, treatment and
      prognosis.

PMID- 21965493
TI  - A meta-analysis of randomized controlled trials shows no evidence that
      periodontal treatment during pregnancy prevents adverse pregnancy outcomes.
AB  - SYSTEMATIC REVIEW CONCLUSION: Treatment of periodontal disease with scaling and
      root planing (SRP) during pregnancy is unlikely to reduce the risk of preterm
      birth or low birth weight. CRITICAL SUMMARY ASSESSMENT: A meta-analysis of 11
      randomized controlled trials, including recently published high-quality studies,
      showed no evidence that SRP during pregnancy prevents preterm birth or other
      adverse pregnancy outcomes. EVIDENCE QUALITY RATING: Good.

PMID- 21965494
TI  - Restoration longevity versus esthetics: a dilemma for dentists and patients.

PMID- 21965495
TI  - Changing of the guard. What should a dental office do to handle the departure of
      a long-term employee?

PMID- 21965496
TI  - Are advertisements that offer 'free second opinions' ethical?

PMID- 21965497
TI  - Avoiding confusion in COPD: from risk factors to phenotypes to measures of
      disease characterisation.

PMID- 21965498
TI  - Tuberculosis in prisons: anatomy of global neglect.

PMID- 21965499
TI  - Healthcare-associated pneumonia: meeting the yeti.

PMID- 21965500
TI  - Infection and remodelling: a 21st century model of bronchiectasis?

PMID- 21965501
TI  - Assessing an outbreak of tuberculosis in an English college population.

PMID- 21965502
TI  - Sputum induction in severe exacerbations of asthma: safety of a modified method.

PMID- 21965503
TI  - Interleukin-18 and interleukin-18 receptor-alpha expression in allergic asthma.

PMID- 21965504
TI  - Pulmonary malakoplakia: a rare presentation mimicking extensive stage IV lung
      cancer.

PMID- 21965505
TI  - Interstitial lung disease in a child heterozygous for the 1549C-->GAA (121ins2)
      mutation of surfactant protein B.

PMID- 21965506
TI  - Ambulatory oxygen in interstitial lung disease.

PMID- 21965509
TI  - Asthma nervosum.

PMID- 21965507
TI  - Another view on the prediction of outcomes in patients with community-acquired
      pneumonia.

PMID- 21965510
TI  - Respiratory Chlamydophyla pneumoniae resides primarily in the lower airway.

PMID- 21965513
TI  - Mitosomes in trophozoites and cysts of the reptilian parasite Entamoeba invadens.
AB  - Heat shock protein genes led to the discovery of mitosomes in Entamoeba
      histolytica, but mitosomes have not been described for any other Entamoeba
      species, nor have they been identified in the cyst stage. Here, we show that the
      distantly related reptilian pathogen Entamoeba invadens contains mitosomes, in
      both trophozoites and cysts, suggesting all Entamoeba species contain these
      organelles.

PMID- 21965514
TI  - Global analysis of serine-threonine protein kinase genes in Neurospora crassa.
AB  - Serine/threonine (S/T) protein kinases are crucial components of diverse
      signaling pathways in eukaryotes, including the model filamentous fungus
      Neurospora crassa. In order to assess the importance of S/T kinases to Neurospora
      biology, we embarked on a global analysis of 86 S/T kinase genes in Neurospora.
      We were able to isolate viable mutants for 77 of the 86 kinase genes. Of these,
      57% exhibited at least one growth or developmental phenotype, with a relatively
      large fraction (40%) possessing a defect in more than one trait. S/T kinase
      knockouts were subjected to chemical screening using a panel of eight chemical
      treatments, with 25 mutants exhibiting sensitivity or resistance to at least one
      chemical. This brought the total percentage of S/T mutants with phenotypes in our
      study to 71%. Mutants lacking apg-1, an S/T kinase required for autophagy in
      other organisms, possessed the greatest number of phenotypes, with defects in
      asexual and sexual growth and development and in altered sensitivity to five
      chemical treatments. We showed that NCU02245/stk-19 is required for chemotropic
      interactions between female and male cells during mating. Finally, we
      demonstrated allelism between the S/T kinase gene NCU00406 and velvet (vel),
      encoding a p21-activated protein kinase (PAK) gene important for asexual and
      sexual growth and development in Neurospora.

PMID- 21965516
TI  - Impact of healthy lifestyle on mortality in people with normal blood pressure,
      LDL cholesterol, and C-reactive protein.
AB  - BACKGROUND: To investigate the impact of healthy lifestyle on cardiovascular risk
      and mortality in people without a history of cardiovascular disease and without
      elevation of lipid, blood pressure, or inflammatory markers. DESIGN: Cohort
      study. METHODS: Study of a diverse sample of adults in the NHANES III follow-up
      Mortality Survey, to determine the benefit of adhering to healthy lifestyle
      habits (five or more fruits and vegetables/day, regular exercise, or being non
      obese (body mass index 18.5-29.9 kg/m(2)), no current smoking, moderate alcohol
      consumption) in adults without common cardiovascular risk factors such as
      elevated cholesterol (low-density lipoprotein, LDL, cholesterol >130 mg/dl),
      inflammation (C-reactive protein, CRP, >3.0 mg/l, or hypertension (blood pressure
      >140/90 mmHg). RESULTS: Of 11,841 participants, 14.9% were adherent to all five
      healthy habits. After controlling for age, race, and gender, individuals with
      lower LDL cholesterol (HR 6.33, 95% CI 2.80-14.30), low CRP (HR 3.48, 95% CI 2.23
      5.41), or normal blood pressure (HR 2.87, 95% CI 1.58-5.20) and 0-1 healthy
      habits had significantly higher all-cause (shown) and cardiovascular mortality
      than people adhering to all five healthy habits. People without common risk
      factors and lacking only 1-2 of the healthy habits remained at higher risk of all
      cause mortality. CONCLUSIONS: People without a history of cardiovascular disease
      who lack common cardiovascular risk factors remain at significantly greater risk
      of cardiovascular and all-cause mortality if they do not adhere to a healthy
      lifestyle. Strategies to encourage adopting healthy lifestyles should be
      implemented among individuals across all risk levels.

PMID- 21965515
TI  - Functional analysis of the exported type IV HSP40 protein PfGECO in Plasmodium
      falciparum gametocytes.
AB  - During Plasmodium falciparum infection, host red blood cell (RBC) remodeling is
      required for the parasite's survival. Such modifications are mediated by the
      export of parasite proteins into the RBC that alter the architecture of the RBC
      membrane and enable cytoadherence. It is probable that some exported proteins
      also play a protective role against the host defense response. This may be of
      particular importance for the gametocyte stage of the life cycle that is
      responsible for malaria transmission, since the gametocyte remains in contact
      with blood as it proceeds through five morphological stages (I to V) during its
      12-day maturation. Using microarray analysis, we identified several genes with
      encoded secretory or export sequences that were differentially expressed during
      early gametocytogenesis. One of these, PfGECO, encodes a predicted type IV heat
      shock protein 40 (HSP40) that we show is expressed in gametocyte stages I to IV
      and is exported to the RBC cytoplasm. HSPs are traditionally induced under
      stressful conditions to maintain homeostasis, but PfGECO expression was not
      increased upon heat shock, suggesting an alternate function. Targeted disruption
      of PfGECO indicated that the gene is not essential for gametocytogenesis in
      vitro, and quantitative reverse transcriptase PCR (RT-PCR) showed that there was
      no compensatory expression of the other type IV HSP40 genes. Although P.
      falciparum HSP40 members are implicated in the trafficking of proteins to the RBC
      surface, removal of PfGECO did not affect the targeting of other exported
      gametocyte proteins. This work has expanded the repertoire of known gametocyte
      exported proteins to include a type IV HSP40, PfGECO.

PMID- 21965517
TI  - Effects of exercise training started within 2 weeks after acute myocardial
      infarction on myocardial perfusion and left ventricular function: a gated SPECT
      imaging study.
AB  - BACKGROUND: Several studies suggested that exercise training might improve
      myocardial perfusion by inducing coronary vascular adaptations or enhancing
      collateralization. However, these findings were obtained in patients with chronic
      coronary artery disease using thallium-201 myocardial perfusion scintigraphy. We
      evaluated whether a long-term exercise-based cardiac rehabilitation (CR) started
      early (9 +/- 3 days) after ST elevation acute myocardial infarction (STEMI)
      improves myocardial perfusion and left ventricular (LV) function, evaluated by
      gated single-photon emission computed tomography (SPECT) imaging. DESIGN:
      Randomized controlled study. METHODS: Fifty patients with recent STEMI were
      randomized into two groups: 24 enrolled in a 6-month exercise-based CR programme
      (group T) and 26 discharged with generic instructions for maintaining physical
      activity and correct lifestyle (group C). All patients underwent cardiopulmonary
      exercise test and gated SPECT within 3 weeks after STEMI and at 6-month follow
      up. RESULTS: At follow up, group T showed a significant reduction of stress
      induced ischaemia (p < 0.01) and an improvement in resting and post-stress wall
      motion (both p < 0.005) and resting (p < 0.05) and post-stress wall thickness (p
      < 0.005) score indexes. At follow up, group T showed an improvement in peak
      oxygen consumption (p < 0.0001), O(2) pulse (p < 0.05), and in the slope of
      increase in ventilation over carbon dioxide output (p < 0.001). No changes in
      myocardial perfusion parameters, LV function, and cardiopulmonary indexes were
      observed in group C at follow up. CONCLUSIONS: Six months of exercise training
      early after STEMI reduces stress-induced ischaemia and improves LV wall motion
      and thickness. Exercise-induced changes in myocardial perfusion and function were
      associated with the absence of unfavourable LV remodelling and with the
      improvement of cardiovascular functional capacity.

PMID- 21965518
TI  - Type D personality and health status in cardiovascular disease populations: a
      meta-analysis of prospective studies.
AB  - BACKGROUND: Knowledge of the factors associated with individual differences in
      patient-reported outcomes is essential to identify high-risk patients and improve
      secondary prevention. DESIGN: In this meta-analysis, we examined the association
      between Type D personality and the individual differences in patient-reported
      physical and mental health status among cardiovascular patients. METHODS: A
      computerized search of the literature through PUBMED and PsychINFO (from 1995 to
      May 2011) was performed and prospective studies were selected that analysed the
      association between Type D personality and health status in cardiovascular
      patients. Two separate meta-analyses were performed for the association of Type D
      personality with physical and mental health status, respectively. RESULTS: Of all
      identified studies, ten studies met the selection criteria. The meta-analyses
      showed that Type D was associated with a two-fold increased odds for impaired
      physical health status (3035 patients, OR 1.94, 95% CI 1.49-2.52) and a 2.5-fold
      increased odds for impaired mental health status (2213 patients, OR 2.55, 95% CI
      1.57-4.16). There was no significant heterogeneity between the studies on
      physical health status (Q = 12.78; p = 0.17; I(2 )= 29.59), but there was between
      those on mental health status (Q = 21.91; p = 0.003; I(2 )= 68.04). Subgroup
      analyses showed that the association between Type D and mental health status
      decreased yet remained significant when adjusting for baseline health status.
      CONCLUSION: Type D personality was shown to be an independent correlate of
      impaired patient-reported physical and mental health status in various
      cardiovascular patient groups. Clinicians should be aware of the association
      between chronic psychological distress and poor patient-reported outcomes.

PMID- 21965520
TI  - Efficacy of perceptive rehabilitation in the treatment of chronic nonspecific low
      back pain through a new tool: a randomized clinical study.
AB  - OBJECTIVE: To evaluate the efficacy of a perceptive rehabilitative approach,
      based on a new device, with regard to pain and disability in patients with
      chronic nonspecific low back pain. DESIGN: Single blind, randomized, controlled
      trial. SETTING: An outpatient academic hospital. PATIENTS: Seventy-five patients
      with chronic low back pain. INTERVENTIONS: Patients were randomized into three
      groups. Twenty-five subjects received 10 sessions in one month, based on specific
      perceptive exercises that were performed on a suitably developed device. Twenty
      five patients entered a Back School programme. Twenty-five patients comprised a
      control group that received the same medical and pharmacological assistance as
      the other groups. MAIN OUTCOME MEASURES: Pain was assessed using the Visual
      Analogue Scale and McGill Pain Questionnaire. Disability was evaluated using the
      Oswestry Disability Index and Waddell Disability Index. All measurements were
      recorded before treatment, at the end of the study, and at 12 and 24 weeks.
      RESULTS: General pain relief was recorded in all the groups, which was elicited
      more quickly in the perceptive treatment group; significant differences in pain
      scores were observed at the end of treatment (P < 0.001 for visual analogue scale
      and P = 0.001 for Questionnaire) versus the other groups. Disability scores in
      the perceptive group did not differ significantly from those in the other group,
      whereas these scores significantly differed between Back School and control
      groups at the follow-ups (P < 0.01 for both scales). CONCLUSION: Perceptive
      rehabilitation has immediate positive effects on pain. Back School reduces
      disabilities at follow-up.

PMID- 21965519
TI  - Incidence and case fatality after day 28 of first time myocardial infarction in
      Sweden 1987-2008.
AB  - AIMS: We studied trends in first-time myocardial infarction (MI) incidence and
      case fatality after day 28 and to examine the role of sex, education as an
      indicator for socioeconomic position, and birth country on these events in
      Sweden. METHODS AND RESULTS: Nationwide cohort including 6,752,655 individuals
      aged 35-89 years living in Sweden between January 1987 and December 2008, of
      which, 6,464,968 individuals and 366,085 nonfatal first-time MI patients were
      classified according to their sex, birth country, and education and followed over
      two decades. MAIN OUTCOME MEASURES: Incidence and case-fatality rate after day 28
      of first-time MI and their trends. A decreasing trend for first-time MI incidence
      and case fatality after day 28 for both sexes regardless of birth country was
      observed (p-trend<0.0001). The trend was, however, less pronounced among female
      and foreign-born. Men had higher incidence than women (incidence rate ratio, IRR
      2.09, 95% CI 2.08-2.11). Men born in Southern and Western Asia had 50% (95% CI 40
      60%) higher risk than men born in Sweden. Incidence was 50-80% higher in the
      least educated irrespective of sex and birth country (p-trend<0.0001). This
      association was stronger for female and foreign-born. We observed a 15% higher
      case fatality after day 28 among men than women (hazard ratio, HR 1.15, 95% CI
      1.13-1.17) and 20-40% lower case fatality after day 28 among patients with no
      diabetes. Low education was associated with 50% higher case fatality after day 28
      regardless of sex and birth country (p-trend <0.0001). CONCLUSION: Although
      incidence of, and fatality after, first-time MI continued to decrease, low
      socioeconomic position, independent of birth country and sex, remained an
      important risk indicator for both events.

PMID- 21965521
TI  - Structural MRI reveals cortical thinning in amyotrophic lateral sclerosis.
AB  - OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a fatal disease characterised
      by combined upper and lower motor neuron degeneration. An early and accurate
      diagnosis is important for patient care and might facilitate the search for a
      more effective therapy. MRI was used to study the whole cortical mantle, applying
      an unbiased surface based approach to identify a marker of upper motor neuron
      involvement in ALS. METHODS: Surface based cortical morphology analyses were
      performed on structural, 3T MRI data of 45 patients with ALS and 25 matched
      healthy controls in a case control study design. These analyses consisted of
      measuring cortical thickness, surface area and volume. The effects of disease
      progression were examined by correlating cortical measures with progression rate
      and by longitudinal measures in 20 patients. RESULTS: Cortical morphology
      analyses revealed specific thinning in the precentral gyrus, considered the
      primary motor cortex, in patients with ALS compared with controls (p=6.3*10(-8)).
      Surface area was reduced in the right inferior parietal region (p=0.049) and
      volume--the product of cortical thickness and surface area--was reduced in the
      right precentral gyrus (p=0.031). From these findings, it appears that cortical
      thickness is superior in detecting the degenerative effects of ALS. Relative
      cortical thinning in temporal regions was related to faster clinical progression
      (right inferior temporal gyrus: p=3.3*10(-4)). CONCLUSIONS: Cortical thinning of
      the primary motor cortex might be a diagnostic marker for upper motor neuron
      degeneration in ALS. Relative thinning in temporal regions was associated with a
      rapidly progressive disease course.

PMID- 21965522
TI  - Risk factors for spinal cord lesions in dystonic cerebral palsy and generalised
      dystonia.
AB  - BACKGROUND: Cervical myelopathy (CM) in patients with cerebral palsy (CP) is
      underdiagnosed as symptoms of spinal cord lesions, being similar to those due to
      dystonia, may be overlooked or identified late. The aim of this study is to
      identify the risk factors and clinical characteristics of CM in patients with
      generalised dystonia, including dystonic CP. METHODS: The authors conducted a
      case-control study to identify early clinical signs of CM in consecutive patients
      with generalised dystonia. The authors compared the clinical characteristics and
      symptoms of those who developed CM (cases) and those who did not (controls). The
      same clinical information on possible neurological manifestations of CM was
      collected for cases and controls at the date of the last visit. RESULTS: Out of
      54 patients, 17 (31%) developed symptomatic CM during the study period. In all
      cases, CM occurred after the age of 36 years. 81% of cases and 35% of controls
      had a Burke-Fahn-Marsden movement subscore for the neck >4. Age (OR per 10
      years=2.3, 95% CI 1.4 to 4.2, p=0.006) and severity of neck dystonia (OR=7.7, 95%
      CI 1.7 to 49.6, p=0.005) were the main risk factors of CM. Gait disorders and
      falls, wasting of hand muscles and bladder disorders were the best clinical clues
      of CM. CONCLUSIONS: As severity of cervical dystonia and age are the major risk
      factors for spinal cord lesions, dystonic patients, including patients with
      dystonic CP, should be screened for CM from the third decade of life onwards.
      Early recognition of CM is crucial for functional prognosis and impact on
      autonomy.

PMID- 21965523
TI  - Obsessive compulsive disorder and psychopathic behaviour in Babylon.
AB  - BACKGROUND: The history of obsessive compulsive, phobic and psychopathic
      behaviour can be traced to the 17th century AD. METHODS AND RESULTS: We draw
      attention to these behaviours in a Babylonian cuneiform medical text known as
      Shurpu. These three categories were united in the Babylonian mind around the
      concept of the mamit 'oath' idea, the behaviour habits being so unbreakable it
      appeared that the subject had sworn an oath to do or not to do the action
      involved. The behavioural accounts were entirely objective, including what we
      would call immature, antisocial and criminal behaviour, and obsessional
      categories of contamination, aggression, orderliness of objects, sex and
      religion. They do not include subjective descriptions of obsessional thoughts,
      ruminations or the subject's attitude to their own behaviour, which are more
      modern fields of enquiry. CONCLUSIONS: The Babylonians had no understanding of
      brain or psychological function but they were remarkable describers of medical
      disease and behaviour. Although they had both physical and supernatural theories
      of many medical disorders and behaviours, they had an open mind on these
      particular behaviours which they regarded as a 'mystery' yet to be 'resolved'. We
      are not aware of comparable accounts of these behaviours in ancient Egyptian or
      classical medicine. These Babylonian descriptions extend the history of these
      disorders to the first half of the second millennium BC.

PMID- 21965524
TI  - Counsel the genotype, treat the phenotype.

PMID- 21965525
TI  - Clinical trials in acute heart failure: simpler solutions to complex problems.
      Consensus document arising from a European Society of Cardiology cardiovascular
      round-table think tank on acute heart failure, 12 May 2009.
AB  - This European consensus document aims to identify the main reasons for the
      apparent lack of progress in the introduction of new medicines for acute heart
      failure. Relevant issues include not only the heterogeneity of the patient group
      but also the pharmacology of the medicines themselves and the design of the
      trials. Above all, this document attempts to provide some pragmatic solutions to
      this complex syndrome to simplify the execution of meaningful therapeutic
      endeavours in this area of undoubted unmet clinical need in the future.

PMID- 21965526
TI  - Left ventricular systolic and diastolic function, remodelling, and clinical
      outcomes among patients with diabetes following myocardial infarction and the
      influence of direct renin inhibition with aliskiren.
AB  - AIMS: We assessed the relationship between diabetes and cardiac structure and
      function following myocardial infarction (MI) and whether diabetes influences the
      effect of direct renin inhibition on change in left ventricular (LV) size.
      METHODS AND RESULTS: The ASPIRE trial enrolled 820 patients 2-8 weeks after MI
      with ejection fraction <= 45% and randomized them to the direct renin inhibitor
      aliskiren (n= 423) or placebo (n = 397) added to standard medical therapy.
      Echocardiography was performed at baseline and after 36 weeks in 672 patients
      with evaluable paired studies. Compared with non-diabetic patients, diabetic
      patients (n = 214) were at higher risk for a composite of cardiovascular (CV)
      death, heart failure hospitalization, recurrent MI, stroke, or aborted sudden
      death (14 vs. 7%; adjusted hazard ratio 1.63, 95% confidence interval 1.01-2.64,
      P= 0.045), despite similar left ventricular ejection fraction (37.9 +/- 5.3 vs.
      37.6 +/- 5.2%, P= 0.48) and end-systolic volume (ESV) (84 +/- 25 vs. 82 +/- 28
      mL, P= 0.46). Diabetic patients demonstrated greater concentric remodelling
      (relative wall thickness 0.38 +/- 0.07 vs. 0.36 +/- 0.07, P= 0.0002) and evidence
      of higher LV filling pressure (E/E' 11.1 +/- 5.3 vs. 9.1 +/- 4.3, P= 0.0011). At
      36 weeks, diabetic patients experienced similar per cent reduction in ESV overall
      (-4.9 +/- 17.9 vs. -5.5 +/- 16.9, P= 0.67) but tended to experience greater
      reduction in ESV than non-diabetic patients when treated with aliskiren
      (interaction P = 0.08). CONCLUSIONS: Compared with non-diabetic patients,
      diabetic patients are at increased risk of CV events post-MI despite no greater
      LV enlargement or reduction in systolic function. Diabetic patients demonstrate
      greater concentric remodelling and evidence of higher LV filling pressure,
      suggesting diastolic dysfunction as a potential mechanism for the higher risk
      observed among these patients.

PMID- 21965528
TI  - Aurora promotes cell division during recovery from TOR-mediated cell cycle arrest
      by driving spindle pole body recruitment of Polo.
AB  - The coordination of cell division and growth in response to changes in nutrient
      supply is mediated by TOR signalling. In fission yeast, increased nutrient
      provision transiently delays mitotic onset without affecting growth. The result
      is an increase in cell size at division. We find that this block to cell division
      relies upon TOR and MAPK signalling and that mitotic entry during recovery from
      this block is regulated by the Aurora kinase Ark1. We show that Ark1
      phosphorylation of polo kinase Plo1 within the linker region between the kinase
      domain and polo boxes drives Plo1 onto the spindle poles where it promotes
      mitosis. Interestingly, the use of Ark1 to phosphorylate Plo1 and promote mitotic
      entry is dependent on the environment.

PMID- 21965529
TI  - Inducible nitric oxide synthase-nitric oxide signaling mediates the mitogenic
      activity of Rac1 during endochondral bone growth.
AB  - Coordinated proliferation and differentiation of growth plate chondrocytes
      controls endochondral bone growth and final height in humans, and disruption of
      this process results in diseases of the growing and adult skeleton, such as
      chondrodysplasias or osteoarthritis. We had shown recently that chondrocyte
      specific deletion of the gene Rac1 in mice leads to severe dwarfism due to
      reduced chondrocyte proliferation, but the molecular pathways involved remained
      unclear. Here, we demonstrate that Rac1-deficient chondrocytes have severely
      reduced levels of inducible nitric oxide synthase (iNOS) protein and nitric oxide
      (NO) production. NO donors reversed the proliferative effects induced by Rac1
      deficiency, whereas inhibition of NO production mimicked the effects of Rac1 loss
      of function. Examination of the growth plate of iNOS-deficient mice revealed
      reduced chondrocyte proliferation and expression of cyclin D1, resembling the
      phenotype of Rac1-deficient growth plates. Finally, we demonstrate that Rac1-NO
      signaling inhibits the expression of ATF3, a known suppressor of cyclin D1
      expression in chondrocytes. In conclusion, our studies identify the iNOS-NO
      pathway as a novel mediator of mitogenic Rac1 signaling and indicate that it
      could be a target for growth disorder therapies.

PMID- 21965530
TI  - Recovery of mitral isthmus conduction leads to the development of macro-reentrant
      tachycardia after left atrial linear ablation for atrial fibrillation.
AB  - BACKGROUND: Left atrial linear ablation for atrial fibrillation (AF) may be
      proarrhythmic, leading to left atrial macro-reentrant tachycardia (LAT). Whether
      due to failure to achieve block initially or to recovery of conduction after
      ablation is unknown. This study was designed to evaluate the frequency of
      recovery of mitral isthmus (MI) conduction compared with cavo-tricuspid isthmus
      (CTI) conduction, and the relationship between recovery of MI conduction and
      postablation LAT. METHODS AND RESULTS: Of 163 patients with AF who underwent
      circumferential pulmonary vein ablation plus left atrial linear ablation, in whom
      MI and CTI ablation produced bidirectional conduction block, 52 underwent repeat
      ablation for recurrent atrial arrhythmias (AF or LAT). Of these 52 patients,
      coronary sinus ablation was required in 48 to achieve bidirectional MI block at
      the index ablation. During repeat ablation, MI and CTI conduction was assessed in
      sinus rhythm. At repeat ablation, MI conduction had recovered in 38 of 52
      patients, as compared with CTI conduction which recovered in only 12 of 52
      patients (P=0.001). At repeat ablation, the recurrent clinical arrhythmia in 12
      patients was MI-dependent LAT. Recovery of MI conduction was associated with
      development of MI-dependent LAT (P=0.01). CONCLUSIONS: Despite using
      bidirectional conduction block as a procedural end point, recovery of MI
      conduction is common and may lead to LAT after left atrial linear ablation for
      AF. The reason for greater recovery of MI versus CTI conduction is unknown but
      could be due to differences in isthmus anatomy or lower power used for ablation
      in the left versus right atrium.

PMID- 21965531
TI  - Simplified RNA secondary structure mapping by automation of SHAPE data analysis.
AB  - SHAPE (Selective 2'-hydroxyl acylation analysed by primer extension) technology
      has emerged as one of the leading methods of determining RNA secondary structure
      at the nucleotide level. A significant bottleneck in using SHAPE is the complex
      and time-consuming data processing that is required. We present here a modified
      data collection method and a series of algorithms, embodied in a program entitled
      Fast Analysis of SHAPE traces (FAST), which significantly reduces processing
      time. We have used this method to resolve the secondary structure of the first
      ~900 nt of the hepatitis C virus (HCV) genome, including the entire core gene. We
      have also demonstrated the ability of SHAPE/FAST to detect the binding of a small
      molecule inhibitor to the HCV internal ribosomal entry site (IRES). In
      conclusion, FAST allows for high-throughput data processing to match the current
      high-throughput generation of data possible with SHAPE, reducing the barrier to
      determining the structure of RNAs of interest.

PMID- 21965532
TI  - The human histone chaperone sNASP interacts with linker and core histones through
      distinct mechanisms.
AB  - Somatic nuclear autoantigenic sperm protein (sNASP) is a human homolog of the
      N1/N2 family of histone chaperones. sNASP contains the domain structure
      characteristic of this family, which includes a large acidic patch flanked by
      several tetratricopeptide repeat (TPR) motifs. sNASP possesses a unique binding
      specificity in that it forms specific complexes with both histone H1 and histones
      H3/H4. Based on the binding affinities of sNASP variants to histones H1, H3.3, H4
      and H3.3/H4 complexes, sNASP uses distinct structural domains to interact with
      linker and core histones. For example, one of the acidic patches of sNASP was
      essential for linker histone binding but not for core histone interactions. The
      fourth TPR of sNASP played a critical role in interactions with histone H3/H4
      complexes, but did not influence histone H1 binding. Finally, analysis of
      cellular proteins demonstrated that sNASP existed in distinct complexes that
      contained either linker or core histones.

PMID- 21965533
TI  - Saccharomyces cerevisiae Ngl3p is an active 3'-5' exonuclease with a specificity
      towards poly-A RNA reminiscent of cellular deadenylases.
AB  - Deadenylation is the first and rate-limiting step during turnover of mRNAs in
      eukaryotes. In the yeast, Saccharomyces cerevisiae, two distinct 3'-5'
      exonucleases, Pop2p and Ccr4p, have been identified within the Ccr4-NOT
      deadenylase complex, belonging to the DEDD and Exonuclease-Endonuclease
      Phosphatase (EEP) families, respectively. Ngl3p has been identified as a new
      member of the EEP family of exonucleases based on sequence homology, but its
      activity and biological roles are presently unknown. Here, we show using in vitro
      deadenylation assays on defined RNA species mimicking poly-A containing mRNAs
      that yeast Ngl3p is a functional 3'-5' exonuclease most active at slightly acidic
      conditions. We further show that the enzyme depends on divalent metal ions for
      activity and possesses specificity towards poly-A RNA similar to what has been
      observed for cellular deadenylases. The results suggest that Ngl3p is naturally
      involved in processing of poly-adenylated RNA and provide insights into the
      mechanistic variations observed among the redundant set of EEP enzymes found in
      yeast and higher eukaryotes.

PMID- 21965534
TI  - Creating highly specific nucleases by fusion of active restriction endonucleases
      and catalytically inactive homing endonucleases.
AB  - Zinc-finger nucleases and TALE nucleases are produced by combining a specific DNA
      binding module and a non-specific DNA-cleavage module, resulting in nucleases
      able to cleave DNA at a unique sequence. Here a new approach for creating highly
      specific nucleases was pursued by fusing a catalytically inactive variant of the
      homing endonuclease I-SceI, as DNA binding-module, to the type IIP restriction
      enzyme PvuII, as cleavage module. The fusion enzymes were designed to recognize a
      composite site comprising the recognition site of PvuII flanked by the
      recognition site of I-SceI. In order to reduce activity on PvuII sites lacking
      the flanking I-SceI sites, the enzymes were optimized so that the binding of I
      SceI to its sites positions PvuII for cleavage of the composite site. This was
      achieved by optimization of the linker and by introducing amino acid
      substitutions in PvuII which decrease its activity or disturb its dimer
      interface. The most specific variant showed a more than 1000-fold preference for
      the addressed composite site over an unaddressed PvuII site. These results
      indicate that using a specific restriction enzyme, such as PvuII, as cleavage
      module, offers an alternative to the otherwise often used catalytic domain of
      FokI, which by itself does not contribute to the specificity of the engineered
      nuclease.

PMID- 21965535
TI  - N- and C-terminal Upf1 phosphorylations create binding platforms for SMG-6 and
      SMG-5:SMG-7 during NMD.
AB  - Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that detects and
      degrades mRNAs containing premature termination codons (PTCs). SMG-1-mediated
      Upf1 phosphorylation takes place in the decay inducing complex (DECID), which
      contains a ribosome, release factors, Upf1, SMG-1, an exon junction complex (EJC)
      and a PTC-mRNA. However, the significance and the consequence of Upf1
      phosphorylation remain to be clarified. Here, we demonstrate that SMG-6 binds to
      a newly identified phosphorylation site in Upf1 at N-terminal threonine 28,
      whereas the SMG-5:SMG-7 complex binds to phosphorylated serine 1096 of Upf1. In
      addition, the binding of the SMG-5:SMG-7 complex to Upf1 resulted in the
      dissociation of the ribosome and release factors from the DECID complex.
      Importantly, the simultaneous binding of both the SMG-5:SMG-7 complex and SMG-6
      to phospho-Upf1 are required for both NMD and Upf1 dissociation from mRNA. Thus,
      the SMG-1-mediated phosphorylation of Upf1 creates a binding platforms for the
      SMG-5:SMG-7 complex and for SMG-6, and triggers sequential remodeling of the mRNA
      surveillance complex for NMD induction and recycling of the ribosome, release
      factors and NMD factors.

PMID- 21965536
TI  - Integration of sequence-similarity and functional association information can
      overcome intrinsic problems in orthology mapping across bacterial genomes.
AB  - Existing methods for orthologous gene mapping suffer from two general problems:
      (i) they are computationally too slow and their results are difficult to
      interpret for automated large-scale applications when based on phylogenetic
      analyses; or (ii) they are too prone to making mistakes in dealing with complex
      situations involving horizontal gene transfers and gene fusion due to the lack of
      a sound basis when based on sequence similarity information. We present a novel
      algorithm, Global Optimization Strategy (GOST), for orthologous gene mapping
      through combining sequence similarity and contextual (working partners)
      information, using a combinatorial optimization framework. Genome-scale
      applications of GOST show substantial improvements over the predictions by three
      popular sequence similarity-based orthology mapping programs. Our analysis
      indicates that our algorithm overcomes the intrinsic issues faced by sequence
      similarity-based methods, when orthology mapping involves gene fusions and
      horizontal gene transfers. Our program runs as efficiently as the most efficient
      sequence similarity-based algorithm in the public domain. GOST is freely
      downloadable at http://csbl.bmb.uga.edu/~maqin/GOST.

PMID- 21965537
TI  - Phosphorylation of bamboo mosaic virus satellite RNA (satBaMV)-encoded protein
      P20 downregulates the formation of satBaMV-P20 ribonucleoprotein complex.
AB  - Bamboo mosaic virus (BaMV) satellite RNA (satBaMV) depends on BaMV for its
      replication and encapsidation. SatBaMV-encoded P20 protein is an RNA-binding
      protein that facilitates satBaMV systemic movement in co-infected plants. Here,
      we examined phosphorylation of P20 and its regulatory functions. Recombinant P20
      (rP20) was phosphorylated by host cellular kinase(s) in vitro, and matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry and
      mutational analyses revealed Ser-11 as the phosphorylation site. The phosphor
      mimic rP20 protein interactions with satBaMV-translated mutant P20 were affected.
      In overlay assay, the Asp mutation at S11 (S11D) completely abolished the self
      interaction of rP20 and significantly inhibited the interaction with both the WT
      and S11A rP20. In chemical cross-linking assays, S11D failed to oligomerize.
      Electrophoretic mobility shift assay and subsequent Hill transformation analysis
      revealed a low affinity of the phospho-mimicking rP20 for satBaMV RNA.
      Substantial modulation of satBaMV RNA conformation upon interaction with
      nonphospho-mimic rP20 in circular dichroism analysis indicated formation of
      stable satBaMV ribonucleoprotein complexes. The dissimilar satBaMV translation
      regulation of the nonphospho- and phospho-mimic rP20 suggests that
      phosphorylation of P20 in the ribonucleoprotein complex converts the translation
      incompetent satBaMV RNA to messenger RNA. The phospho-deficient or phospho
      mimicking P20 mutant of satBaMV delayed the systemic spread of satBaMV in co
      infected Nicotiana benthamiana with BaMV. Thus, satBaMV likely regulates the
      formation of satBaMV RNP complex during co-infection in planta.

PMID- 21965538
TI  - ATP-regulated interactions between P1 ParA, ParB and non-specific DNA that are
      stabilized by the plasmid partition site, parS.
AB  - Localization of the P1 plasmid requires two proteins, ParA and ParB, which act on
      the plasmid partition site, parS. ParB is a site-specific DNA-binding protein and
      ParA is a Walker-type ATPase with non-specific DNA-binding activity. In vivo ParA
      binds the bacterial nucleoid and forms dynamic patterns that are governed by the
      ParB-parS partition complex on the plasmid. How these interactions drive plasmid
      movement and localization is not well understood. Here we have identified a large
      protein-DNA complex in vitro that requires ParA, ParB and ATP, and have
      characterized its assembly by sucrose gradient sedimentation and light scattering
      assays. ATP binding and hydrolysis mediated the assembly and disassembly of this
      complex, while ADP antagonized complex formation. The complex was not dependent
      on, but was stabilized by, parS. The properties indicate that ParA and ParB are
      binding and bridging multiple DNA molecules to create a large meshwork of protein
      DNA molecules that involves both specific and non-specific DNA. We propose that
      this complex represents a dynamic adaptor complex between the plasmid and
      nucleoid, and further, that this interaction drives the redistribution of
      partition proteins and the plasmid over the nucleoid during partition.

PMID- 21965539
TI  - Structural insights to the metal specificity of an archaeal member of the LigD 3'
      phosphoesterase DNA repair enzyme family.
AB  - LigD 3'-phosphoesterase (PE) enzymes perform end-healing reactions at DNA breaks.
      Here we characterize the 3'-ribonucleoside-resecting activity of Candidatus
      Korarchaeum PE. CkoPE prefers a single-stranded substrate versus a primer
      template. Activity is abolished by vanadate (10 mM), but is less sensitive to
      phosphate (IC(50) 50 mM) or chloride (IC(50) 150 mM). The metal requirement is
      satisfied by manganese, cobalt, copper or cadmium, but not magnesium, calcium,
      nickel or zinc. Insights to CkoPE metal specificity were gained by solving new
      1.5 A crystal structures of CkoPE in complexes with Co(2+) and Zn(2+). His9,
      His15 and Asp17 coordinate cobalt in an octahedral complex that includes a
      phosphate anion, which is in turn coordinated by Arg19 and His51. The cobalt and
      phosphate positions and the atomic contacts in the active site are virtually
      identical to those in the CkoPE.Mn(2+) structure. By contrast, Zn(2+) binds in
      the active site in a tetrahedral complex, wherein the position, orientation and
      atomic contacts of the phosphate are shifted and its interaction with His51 is
      lost. We conclude that: (i) PE selectively binds to 'soft' metals in either
      productive or non-productive modes and (ii) PE catalysis depends acutely on
      proper metal and scissile phosphate geometry.

PMID- 21965540
TI  - TFIIH is an elongation factor of RNA polymerase I.
AB  - TFIIH is a multisubunit factor essential for transcription initiation and
      promoter escape of RNA polymerase II and for the opening of damaged DNA double
      strands in nucleotide excision repair (NER). In this study, we have analyzed at
      which step of the transcription cycle TFIIH is essential for transcription by RNA
      polymerase I. We demonstrate that TFIIH associates with the rDNA promoter and
      gene-internal sequences and leaves the rDNA promoter in a complex with RNA
      polymerase I after start of transcription. Moreover, mutations in the TFIIH
      subunits XPB and XPD found in Cockayne syndrome impair the interaction of TFIIH
      with the rDNA, but do not influence initiation complex formation or promoter
      escape of RNA polymerase I, but preclude the productivity of the enzyme by
      reducing transcription elongation in vivo and in vitro. Our results implicate
      that reduced RNA polymerase I transcription elongation and ribosomal stress could
      be one factor contributing to the Cockayne syndrome phenotype.

PMID- 21965541
TI  - Transposon Ac/Ds-induced chromosomal rearrangements at the rice OsRLG5 locus.
AB  - Previous studies have shown that pairs of closely-linked Ac/Ds transposable
      elements can induce various chromosomal rearrangements in plant genomes. To study
      chromosomal rearrangements in rice, we isolated a line (OsRLG5-161) that contains
      two inversely-oriented Ds insertions in OsRLG5 (Oryza sativa Receptor like kinase
      Gene 5). Among approximately 300 plants regenerated from OsRLG5-161 heterozygous
      seeds, 107 contained rearrangements including deletions, duplications and
      inversions of various sizes. Most rearrangements were induced by previously
      identified alternative transposition mechanism. Furthermore, we also detected a
      new class of rearrangements that contain juxtaposed inversions and deletions on
      the same chromosome. We propose that these novel alleles were generated by a
      previously unreported type of alternative transposition reactions involving the
      5' and 3' termini of two inversely-oriented Ds elements located on the same
      chromatid. Finally, 11% of rearrangements contained inversions resulting from
      homologous recombination between the two inverted Ds elements in OsRLG5-161. The
      high frequency inheritance and great variety of rearrangements obtained suggests
      that the rice regeneration system results in a burst of transposition activity
      and a relaxation of the controls which normally limit the transposition
      competence of individual Ds termini. Together, these results demonstrate a
      greatly enlarged potential of the Ac/Ds system for plant chromosome engineering.

PMID- 21965543
TI  - Mortality amenable to health care and its relation to socio-economic status in
      Hungary, 2004-08.
AB  - BACKGROUND: Recently, research focus has returned to amenable mortality to health
      care, despite the decreasing trend, as it remains a significant contributor to
      social and economic loss due to premature death. This article assesses the trends
      of amenable mortality over time and, its spatial inequalities with respect to
      deprivation, in Hungary. METHODS: An ecological analysis of mortality amenable to
      health care was carried out using smoothed indirectly standardized mortality
      ratios, calculated by full hierarchical Bayesian methods, at municipality level.
      The association between the spatial distribution of amenable mortality and
      deprivation was also assessed using a Hungarian specific deprivation index.
      RESULTS: Trends of mortality amenable to health care were characterized by a
      decreasing pattern across the studied period, 1996-2008. Areas of significantly
      high risk of amenable mortality were identified in the North-eastern, Eastern and
      South-western parts of Hungary. A statistically significant association was found
      between amenable mortality and deprivation status in both genders. After
      correcting for bias due to socio-economic confounders, the patterns of areas with
      excess risks significantly changed. CONCLUSION: Differences in deprivation alone
      cannot explain the spatial distribution of mortality amenable to health care.
      This study highlights the importance of exploring other factors (e.g. health-care
      system and individual life style) beyond socio-economic status, which affect
      health inequalities particularly for health policy makers, who are responsible
      for the mitigation of health disparities.

PMID- 21965542
TI  - Structural basis for nematode eIF4E binding an m(2,2,7)G-Cap and its implications
      for translation initiation.
AB  - Metazoan spliced leader (SL) trans-splicing generates mRNAs with an m(2,2,7)G-cap
      and a common downstream SL RNA sequence. The mechanism for eIF4E binding an m227G
      cap is unknown. Here, we describe the first structure of an eIF4E with an
      m(2,2,7)G-cap and compare it to the cognate m7G-eIF4E complex. These structures
      and Nuclear Magnetic Resonance (NMR) data indicate that the nematode Ascaris suum
      eIF4E binds the two different caps in a similar manner except for the loss of a
      single hydrogen bond on binding the m(2,2,7)G-cap. Nematode and mammalian eIF4E
      both have a low affinity for m(2,2,7)G-cap compared with the m7G-cap. Nematode
      eIF4E binding to the m7G-cap, m(2,2,7)G-cap and the m(2,2,7)G-SL 22-nt RNA leads
      to distinct eIF4E conformational changes. Additional interactions occur between
      Ascaris eIF4E and the SL on binding the m(2,2,7)G-SL. We propose interactions
      between Ascaris eIF4E and the SL impact eIF4G and contribute to translation
      initiation, whereas these interactions do not occur when only the m(2,2,7)G-cap
      is present. These data have implications for the contribution of 5'-UTRs in mRNA
      translation and the function of different eIF4E isoforms.

PMID- 21965544
TI  - Representativeness of participants in a cross-sectional health survey by time of
      day and day of week of data collection.
AB  - BACKGROUND: General population health examination surveys (HESs) provide a
      reliable source of information to monitor the health of populations. A number of
      countries across Europe are currently planning their first HES, or the first
      after a significant gap, and some of these intend offering appointments only
      during office hours and/or weekdays, raising concerns about representativeness of
      survey participants. It is important to ascertain whether personal
      characteristics of participants vary by time of day and day of week of data
      collection, in order to determine the association between time and day of
      interview and physical examination on the results of data collected in HES.
      METHODS: Multivariable regression models were applied to national HES in England
      to examine socio-demographic and health variations in three combined day-time
      periods of interview and physical examination: weekday daytime; weekday evening;
      and weekend. RESULTS: The characteristics of participants interviewed or visited
      by a nurse varied by both time of day and day of the week for age, ethnicity,
      marital status, income, socio-economic group, economic activity and deprivation.
      People seen during weekday working hours had higher rates of poor self-reported
      health, limiting longstanding illness and obesity, and higher alcohol
      consumption, BMI and systolic blood pressure; adjustment for socio-demographic
      characteristics eliminated or substantially reduced these differences.
      CONCLUSION: People responsible for planning surveys should be aware of
      participant preference for the timing of data collection and ensure flexibility
      and choice in times and days offered to optimise participation rates and
      representativeness.

PMID- 21965545
TI  - The mammalian START domain protein family in lipid transport in health and
      disease.
AB  - Lipid transfer proteins of the steroidogenic acute regulatory protein-related
      lipid transfer (START) domain family are defined by the presence of a conserved
      ~210 amino acid sequence that folds into an alpha/beta helix-grip structure
      forming a hydrophobic pocket for ligand binding. The mammalian START proteins
      bind diverse ligands, such as cholesterol, oxysterols, phospholipids,
      sphingolipids, and possibly fatty acids, and have putative roles in non-vesicular
      lipid transport, thioesterase enzymatic activity, and tumor suppression. However,
      the biological functions of many members of the START domain protein family are
      not well established. Recent research has focused on characterizing the cell-type
      distribution and regulation of the START proteins, examining the specificity and
      directionality of lipid transport, and identifying disease states associated with
      dysregulation of START protein expression. This review summarizes the current
      concepts of the proposed physiological and pathological roles for the mammalian
      START domain proteins in cholesterol and lipid trafficking.

PMID- 21965546
TI  - Testosterone enhances estradiol's cardioprotection in ovariectomized rats.
AB  - After menopause, the development of cardiovascular disease (CVD) is due not only
      to estrogen decline but also to androgen decline. This study examined the effects
      of either estradiol (E(2)) or testosterone replacement alone or E(2)-testosterone
      combination on isolated myocytes in ovariectomized (Ovx) rats subjected to
      ischemia/reperfusion (I/R). Furthermore, we determined whether the effects are
      associated with beta(2)-adrenoceptor (beta(2)-AR). Five groups of adult female
      Sprague-Dawley rats were used: Sham operation (Sham) rats, bilateral Ovx rats,
      Ovx rats with E(2) 40 MUg/kg per day (Ovx+E), Ovx rats with testosterone 150
      MUg/kg per day (Ovx+T), and Ovx rats with E(2) 40 MUg/kg per day+testosterone 150
      MUg/kg per day (Ovx+E/T). We determined the lactate dehydrogenase (LDH) release,
      percentage of rod-shaped cells and apoptosis of ventricular myocytes from rats of
      all groups subjected to I/R. Then, we determined the above indices and
      contractile function with or without a selective beta(2)-AR antagonist ICI 118
      551. We also determined the expression of beta(2)-AR. Our data show that either
      E(2) or testosterone replacement alone or E(2) and testosterone in combination
      decreased the LDH release, increased the percentage of rod-shaped cells, reduced
      apoptotic cells (%), and combination treatment appeared to be more effective than
      either E(2) or testosterone replacement alone. ICI 118 551 abolished the effects
      of the three. Combination supplementation also enhanced the expression of beta(2)
      AR. We concluded that in Ovx rats, testosterone enhances E(2)'s cardioprotection,
      while E(2) and testosterone in combination was more effective and the protective
      effects may be associated with beta(2)-AR. The study highlights the potential
      therapeutic application for CVD in postmenopausal women.

PMID- 21965547
TI  - Cortisol, estradiol-17beta, and progesterone secretion within the first hour
      after awakening in women with regular menstrual cycles.
AB  - Cortisol concentration in both serum and saliva sharply increases and reaches a
      peak within the first hour after waking in the morning. This phenomenon is known
      as the cortisol awakening response (CAR) and is used as an index of hypothalamus
      pituitary-adrenal (HPA) axis function. We examined whether ovarian steroid
      concentrations increased after awakening as with the CAR in the HPA axis. To do
      this, cortisol, estradiol-17beta (E(2)), and progesterone (P(4)) concentrations
      were determined in saliva samples collected immediately upon awakening and 30 and
      60 min after awakening in women with regular menstrual cycles and postmenopausal
      women. We found that both E(2) and P(4) concentrations increased during the post
      awakening period in women with regular menstrual cycles, but these phenomena were
      not seen in any postmenopausal women. The area under the E(2) and P(4) curve from
      the time interval immediately after awakening to 60 min after awakening (i.e.
      E(2)auc and P(4)auc) in women with regular menstrual cycles were greater than
      those in the postmenopausal women. E(2) and P(4) secretory activity during the
      post-awakening period was influenced by the phase of the menstrual cycle. E(2)auc
      in the peri-ovulatory phase and P(4)auc in the early to mid-luteal phase were
      greater than in the menstrual phase. Meanwhile, cortisol secretory activity
      during the post-awakening period was not influenced by menstrual status or the
      phase of menstrual cycle. These findings indicate that, as with the CAR in the
      HPA axis function, ovarian steroidogenic activity increased after awakening and
      is closely associated with menstrual status and phase of menstrual cycle.

PMID- 21965548
TI  - Four genetic loci influencing electrocardiographic indices of left ventricular
      hypertrophy.
AB  - BACKGROUND: Presence of left ventricular hypertrophy on an ECG (ECG-LVH) is
      widely assessed clinically and provides prognostic information in some settings.
      There is evidence for significant heritability of ECG-LVH. We conducted a large
      scale gene-centric association analysis of 4 commonly measured indices of ECG
      LVH. METHODS AND RESULTS: We calculated the Sokolow-Lyon index, Cornell product,
      12-lead QRS voltage sum, and 12-lead QRS voltage product in 10 256 individuals
      from 3 population-based cohorts and typed their DNA using a customized gene array
      (the Illumina HumanCVD BeadChip 50K array), containing 49 094 genetic variants in
      ~2100 genes of cardiovascular relevance. We followed-up promising associations in
      11 777 additional individuals. We identified and replicated 4 loci associated
      with ECG-LVH indices: 3p22.2 (SCN5A, rs6797133, P=1.22 * 10(-7)) with Cornell
      product and 12q13.3 (PTGES3, rs2290893, P=3.74 * 10(-8)), 15q25.2 (NMB,
      rs2292462, P=3.23 * 10(-9)), and 15q26.3 (IGF1R, rs4966014, P=1.26 * 10(-7)) with
      the 12-lead QRS voltage sum. The odds ratio of being in the top decile for the 12
      lead QRS voltage sum for those carrying 6 trait-raising alleles at the 12q13.3,
      15q25.2, and 15q26.3 loci versus those carrying 0 to 1 alleles was 1.60 (95% CI:
      1.20 to 2.29). Lead single-nucleotide polymorphisms at the 12q13.3 and 15q25.2
      loci showed significant expression quantitative trait loci effects in monocytes.
      CONCLUSIONS: These findings provide novel insights into the genetic determination
      of ECG-LVH. The findings could help to improve our understanding of the
      mechanisms determining this prognostically important trait.

PMID- 21965549
TI  - Homozygosity mapping and exome sequencing reveal GATAD1 mutation in autosomal
      recessive dilated cardiomyopathy.
AB  - BACKGROUND: Dilated cardiomyopathy (DCM) is a heritable, genetically
      heterogeneous disorder that typically exhibits autosomal dominant inheritance.
      Genomic strategies enable discovery of novel, unsuspected molecular underpinnings
      of familial DCM. We performed genome-wide mapping and exome sequencing in a
      unique family wherein DCM segregated as an autosomal recessive (AR) trait.
      METHODS AND RESULTS: Echocardiography in 17 adult descendants of first cousins
      revealed DCM in 2 female siblings and idiopathic left ventricular enlargement in
      their brother. Genotyping and linkage analysis mapped an AR DCM locus to
      chromosome arm 7q21, which was validated and refined by high-density homozygosity
      mapping. Exome sequencing of the affected sisters was then used as a
      complementary strategy for mutation discovery. An iterative bioinformatics
      process was used to filter >40,000 genetic variants, revealing a single shared
      homozygous missense mutation localized to the 7q21 critical region. The mutation,
      absent in HapMap, 1000 Genomes, and 474 ethnically matched controls, altered a
      conserved residue of GATAD1, encoding GATA zinc finger domain-containing protein
      1. Thirteen relatives were heterozygous mutation carriers with no evidence of
      myocardial disease, even at advanced ages. Immunohistochemistry demonstrated
      nuclear localization of GATAD1 in left ventricular myocytes, yet subcellular
      expression and nuclear morphology were aberrant in the proband. CONCLUSIONS:
      Linkage analysis and exome sequencing were used as synergistic genomic strategies
      to identify GATAD1 as a gene for AR DCM. GATAD1 binds to a histone modification
      site that regulates gene expression. Consistent with murine DCM caused by genetic
      disruption of histone deacetylases, the data implicate an inherited basis for
      epigenetic dysregulation in human heart failure.

PMID- 21965550
TI  - Nurse prescribing in general practice: a qualitative study of job satisfaction
      and work-related stress.
AB  - BACKGROUND: Studies examining the impact nurse prescribing have largely focused
      on the efficacy of the service. It was suggested in pro-prescribing policy
      arguments that extending the nursing role to include prescribing would increase
      job satisfaction. This assertion has not been fully explored. OBJECTIVES: To
      investigate the impact of independent prescribing for experienced nurse
      practitioners (NPs) working in general practice. METHODS: In-depth interviews
      were conducted with six NPs who each had at least 3 years experience of
      independent prescribing in a busy inner city general practice. RESULTS: Analysis
      of interview data yielded two main themes: as independent prescribers NPs
      experienced increased levels of both job satisfaction and work-related stress.
      Increased satisfaction was associated with having greater autonomy and being able
      to provide more holistic care. Increased work-related stress emerged from greater
      job demands, perceived insufficient support and perceived effort-reward imbalance
      that centred upon the enhanced role not being recognized in terms of an increase
      in grade and pay. CONCLUSIONS: Independent prescribing increases job satisfaction
      for NPs in general practice, but there is also evidence of stressors associated
      with the role. It is important that NPs in general practice are encouraged and
      supported towards providing the effective patient-centred care in the community
      envisaged by current UK government. We acknowledge that the results presented in
      this paper are based on a sample limited to one city; however, it provides
      information that has important implications for the well being of NPs and
      ultimately patient care.

PMID- 21965551
TI  - Shared filtering processes link attentional and visual short-term memory capacity
      limits.
AB  - Both visual attention and visual short-term memory (VSTM) have been shown to have
      capacity limits of 4 +/- 1 objects, driving the hypothesis that they share a
      visual processing buffer. However, these capacity limitations also show strong
      individual differences, making the degree to which these capacities are related
      unclear. Moreover, other research has suggested a distinction between attention
      and VSTM buffers. To explore the degree to which capacity limitations reflect the
      use of a shared visual processing buffer, we compared individual subject's
      capacities on attentional and VSTM tasks completed in the same testing session.
      We used a multiple object tracking (MOT) and a VSTM change detection task, with
      varying levels of distractors, to measure capacity. Significant correlations in
      capacity were not observed between the MOT and VSTM tasks when distractor
      filtering demands differed between the tasks. Instead, significant correlations
      were seen when the tasks shared spatial filtering demands. Moreover, these
      filtering demands impacted capacity similarly in both attention and VSTM tasks.
      These observations fail to support the view that visual attention and VSTM
      capacity limits result from a shared buffer but instead highlight the role of the
      resource demands of underlying processes in limiting capacity.

PMID- 21965553
TI  - Introduction to issue on qualitative research and evidence-based practices.

PMID- 21965552
TI  - JWH-018 and JWH-073: Delta9-tetrahydrocannabinol-like discriminative stimulus
      effects in monkeys.
AB  - Products containing naphthalen-1-yl-(1-pentylindol-3-yl) methanone (JWH-018) and
      naphthalen-1-yl-(1-butylindol-3-yl) methanone (JWH-073) are emerging drugs of
      abuse. Here, the behavioral effects of JWH-018 and JWH-073 were examined in one
      behavioral assay selective for cannabinoid agonism, rhesus monkeys (n = 4)
      discriminating Delta9-tetrahydrocannabinol (Delta9-THC; 0.1 mg/kg i.v.), and
      another assay sensitive to cannabinoid withdrawal, i.e., monkeys (n = 3)
      discriminating the cannabinoid antagonist rimonabant (1 mg/kg i.v.) during
      chronic Delta9-THC (1 mg/kg s.c. 12 h) treatment. Delta9-THC, JWH-018, and JWH
      073 increased drug-lever responding in monkeys discriminating Delta9-THC; the
      ED50 values were 0.044, 0.013, and 0.058 mg/kg, respectively and the duration of
      action was 4, 2, and 1 h, respectively. Rimonabant (0.32-3.2 mg/kg) produced
      surmountable antagonism of Delta9-THC, JWH-018, and JWH-073. Schild analyses and
      single-dose apparent affinity estimates yielded apparent pA2/pK(B) values of
      6.65, 6.68, and 6.79 in the presence of Delta9-THC, JWH-018, and JWH-073,
      respectively. In Delta9-THC-treated monkeys discriminating rimonabant, the
      training drug increased responding on the rimonabant lever; the ED50 value of
      rimonabant was 0.20 mg/kg. Delta9-THC (1-10 mg/kg), JWH-018 (0.32-3.2 mg/kg), and
      JWH-073 (3.2-32 mg/kg) dose-dependently attenuated the rimonabant-discriminative
      stimulus (i.e., withdrawal). These results suggest that Delta9-THC, JWH-018, and
      JWH-073 act through the same receptors to produce Delta9-THC-like subjective
      effects and attenuate Delta9-THC withdrawal. The relatively short duration of
      action of JWH-018 and JWH-073 might lead to more frequent use, which could
      strengthen habitual use by increasing the frequency of stimulus-outcome pairings.
      This coupled with the possible greater efficacy of JWH-018 at cannabinoid 1
      receptors could be associated with greater dependence liability than Delta9-THC.

PMID- 21965554
TI  - Brain natriuretic peptide and breathing not properly: the merger of 2 BNPs.

PMID- 21965555
TI  - Analytical characteristics of high-sensitivity cardiac troponin assays.
AB  - BACKGROUND: Cardiac troponins I (cTnI) and T (cTnT) have received international
      endorsement as the standard biomarkers for detection of myocardial injury, for
      risk stratification in patients suspected of acute coronary syndrome, and for the
      diagnosis of myocardial infarction. An evidence-based clinical database is
      growing rapidly for high-sensitivity (hs) troponin assays. Thus, clarifications
      of the analytical principles for the immunoassays used in clinical practice are
      important. CONTENT: The purpose of this mini-review is (a) to provide a
      background for the biochemistry of cTnT and cTnI and (b) to address the following
      analytical questions for both hs cTnI and cTnT assays: (i) How does an assay
      become designated hs? (ii) How does one realistically define healthy (normal)
      reference populations for determining the 99th percentile? (iii) What is the
      usual biological variation of these analytes? (iv) What assay imprecision
      characteristics are acceptable? (v) Will standardization of cardiac troponin
      assays be attainable? SUMMARY: This review raises important points regarding cTnI
      and cTnT assays and their reference limits and specifically addresses hs assays
      used to measure low concentrations (nanograms per liter or picograms per
      milliliter). Recommendations are made to help clarify the nomenclature. The
      review also identifies further challenges for the evolving science of cardiac
      troponin measurement. It is hoped that with the introduction of these concepts,
      both laboratorians and clinicians can develop a more unified view of how these
      assays are used worldwide in clinical practice.

PMID- 21965556
TI  - Proficiency testing/external quality assessment: current challenges and future
      directions.
AB  - BACKGROUND: Proficiency testing (PT), or external quality assessment (EQA), is
      intended to verify on a recurring basis that laboratory results conform to
      expectations for the quality required for patient care. CONTENT: Key factors for
      interpreting PT/EQA results are knowledge of the commutability of the samples
      used and the process used for target value assignment. A commutable PT/EQA sample
      demonstrates the same numeric relationship between different measurement
      procedures as that expected for patients' samples. Noncommutable PT/EQA samples
      frequently have a matrix-related bias of unknown magnitude that limits
      interpretation of results. PT/EQA results for commutable samples can be used to
      assess accuracy against a reference measurement procedure or a designated
      comparison method. In addition, the agreement of the results between different
      measurement procedures for commutable samples reflects that which would be seen
      for patients' samples. PT/EQA results for noncommutable samples must be compared
      to a peer group mean/median of results from participants who use measurement
      procedures that are expected to have the same or very similar matrix-related
      bias. Peer group evaluation is used to asses whether a laboratory is using a
      measurement procedure in conformance to the manufacturer's specifications and/or
      in conformance to other laboratories using the same technology. A noncommutable
      PT/EQA sample does not give meaningful information about the relationship of
      results for patients' samples between different measurement procedures. SUMMARY:
      PT/EQA provides substantial value to the practice of laboratory medicine by
      assessing the performance of individual laboratories and, when commutable samples
      are used, the status of standardization or harmonization among different
      measurement procedures.

PMID- 21965557
TI  - QlicRice: a web interface for abiotic stress responsive QTL and loci interaction
      channels in rice.
AB  - The QlicRice database is designed to host publicly accessible, abiotic stress
      responsive quantitative trait loci (QTLs) in rice (Oryza sativa) and their
      corresponding sequenced gene loci. It provides a platform for the data mining of
      abiotic stress responsive QTLs, as well as browsing and annotating associated
      traits, their location on a sequenced genome, mapped expressed sequence tags
      (ESTs) and tissue and growth stage-specific expressions on the whole genome.
      Information on QTLs related to abiotic stresses and their corresponding loci from
      a genomic perspective has not yet been integrated on an accessible, user-friendly
      platform. QlicRice offers client-responsive architecture to retrieve meaningful
      biological information--integrated and named 'Qlic Search'--embedded in a query
      phrase autocomplete feature, coupled with multiple search options that include
      trait names, genes and QTL IDs. A comprehensive physical and genetic map and
      vital statistics have been provided in a graphical manner for deciphering the
      position of QTLs on different chromosomes. A convenient and intuitive user
      interface have been designed to help users retrieve associations to agronomically
      important QTLs on abiotic stress response in rice. Database URL:
      http://nabg.iasri.res.in:8080/qlic-rice/.

PMID- 21965558
TI  - Bacteriophage F336 recognizes the capsular phosphoramidate modification of
      Campylobacter jejuni NCTC11168.
AB  - Bacteriophages infecting the food-borne human pathogen Campylobacter jejuni could
      potentially be exploited to reduce bacterial counts in poultry prior to
      slaughter. This bacterium colonizes the intestinal tract of poultry in high
      numbers, and contaminated poultry meat is regarded as the major source of human
      campylobacteriosis. In this study, we used phage F336 belonging to the Myoviridae
      family to select a C. jejuni NCTC11168 phage-resistant strain, called 11168R,
      with the aim of investigating the mechanisms of phage resistance. We found that
      phage F336 has reduced adsorption to 11168R, thus indicating that the receptor is
      altered. While proteinase K-treated C. jejuni cells did not affect adsorption,
      periodate treatment resulted in reduced adsorption, suggesting that the phage
      binds to a carbohydrate moiety. Using high-resolution magic angle spinning
      nuclear magnetic resonance (NMR) spectroscopy, we found that 11168R lacks an O
      methyl phosphoramidate (MeOPN) moiety attached to the GalfNAc on the capsular
      polysaccharide (CPS), which was further confirmed by mass spectroscopy. Sequence
      analysis of 11168R showed that the potentially hypervariable gene cj1421, which
      encodes the GalfNAc MeOPN transferase, contains a tract of 10 Gs, resulting in a
      nonfunctional gene product. However, when 11168R reverted back to phage
      sensitive, cj1421 contained 9 Gs, and the GalfNAc MeOPN was regained in this
      strain. In summary, we have identified the phase-variable MeOPN moiety, a common
      component of the diverse capsular polysaccharides of C. jejuni, as a novel
      receptor of phages infecting this bacterium.

PMID- 21965559
TI  - Ab initio structural modeling of and experimental validation for Chlamydia
      trachomatis protein CT296 reveal structural similarity to Fe(II) 2-oxoglutarate
      dependent enzymes.
AB  - Chlamydia trachomatis is a medically important pathogen that encodes a relatively
      high percentage of proteins with unknown function. The three-dimensional
      structure of a protein can be very informative regarding the protein's functional
      characteristics; however, determining protein structures experimentally can be
      very challenging. Computational methods that model protein structures with
      sufficient accuracy to facilitate functional studies have had notable successes.
      To evaluate the accuracy and potential impact of computational protein structure
      modeling of hypothetical proteins encoded by Chlamydia, a successful
      computational method termed I-TASSER was utilized to model the three-dimensional
      structure of a hypothetical protein encoded by open reading frame (ORF) CT296.
      CT296 has been reported to exhibit functional properties of a divalent cation
      transcription repressor (DcrA), with similarity to the Escherichia coli iron
      responsive transcriptional repressor, Fur. Unexpectedly, the I-TASSER model of
      CT296 exhibited no structural similarity to any DNA-interacting proteins or
      motifs. To validate the I-TASSER-generated model, the structure of CT296 was
      solved experimentally using X-ray crystallography. Impressively, the ab initio I
      TASSER-generated model closely matched (2.72-A C(alpha) root mean square
      deviation [RMSD]) the high-resolution (1.8-A) crystal structure of CT296. Modeled
      and experimentally determined structures of CT296 share structural
      characteristics of non-heme Fe(II) 2-oxoglutarate-dependent enzymes, although key
      enzymatic residues are not conserved, suggesting a unique biochemical process is
      likely associated with CT296 function. Additionally, functional analyses did not
      support prior reports that CT296 has properties shared with divalent cation
      repressors such as Fur.

PMID- 21965560
TI  - Deletion strains reveal metabolic roles for key elemental sulfur-responsive
      proteins in Pyrococcus furiosus.
AB  - Transcriptional and enzymatic analyses of Pyrococcus furiosus previously
      indicated that three proteins play key roles in the metabolism of elemental
      sulfur (S(0)): a membrane-bound oxidoreductase complex (MBX), a cytoplasmic
      coenzyme A-dependent NADPH sulfur oxidoreductase (NSR), and sulfur-induced
      protein A (SipA). Deletion strains, referred to as MBX1, NSR1, and SIP1,
      respectively, have now been constructed by homologous recombination utilizing the
      uracil auxotrophic COM1 parent strain (DeltapyrF). The growth of all three
      mutants on maltose was comparable without S(0), but in its presence, the growth
      of MBX1 was greatly impaired while the growth of NSR1 and SIP1 was largely
      unaffected. In the presence of S(0), MBX1 produced little, if any, sulfide but
      much more acetate (per unit of protein) than the parent strain, demonstrating
      that MBX plays a critical role in S(0) reduction and energy conservation. In
      contrast, comparable amounts of sulfide and acetate were produced by NSR1 and the
      parent strain, indicating that NSR is not essential for energy conservation
      during S(0) reduction. Differences in transcriptional responses to S(0) in NSR1
      suggest that two sulfide dehydrogenase isoenzymes provide a compensatory NADPH
      dependent S(0) reduction system. Genes controlled by the S(0)-responsive
      regulator SurR were not as highly regulated in MBX1 and NSR1. SIP1 produced the
      same amount of acetate but more sulfide than the parent strain. That SipA is not
      essential for growth on S(0) indicates that it is not required for detoxification
      of metal sulfides, as previously suggested. A model is proposed for S(0)
      reduction by P. furiosus with roles for MBX and NSR in bioenergetics and for SipA
      in iron-sulfur metabolism.

PMID- 21965561
TI  - Phenol sensing by Escherichia coli chemoreceptors: a nonclassical mechanism.
AB  - The four transmembrane chemoreceptors of Escherichia coli sense phenol as either
      an attractant (Tar) or a repellent (Tap, Trg, and Tsr). In this study, we
      investigated the Tar determinants that mediate its attractant response to phenol
      and the Tsr determinants that mediate its repellent response to phenol. Tar
      molecules with lesions in the aspartate-binding pocket of the periplasmic domain,
      with a foreign periplasmic domain (from Tsr or from several Pseudomonas
      chemoreceptors), or lacking nearly the entire periplasmic domain still mediated
      attractant responses to phenol. Similarly, Tar molecules with the cytoplasmic
      methylation and kinase control domains of Tsr still sensed phenol as an
      attractant. Additional hybrid receptors with signaling elements from both Tar and
      Tsr indicated that the transmembrane (TM) helices and HAMP domain determined the
      sign of the phenol-sensing response. Several amino acid replacements in the HAMP
      domain of Tsr, particularly attractant-mimic signaling lesions at residue E248,
      converted Tsr to an attractant sensor of phenol. These findings suggest that
      phenol may elicit chemotactic responses by diffusing into the cytoplasmic
      membrane and perturbing the structural stability or position of the TM bundle
      helices, in conjunction with structural input from the HAMP domain. We conclude
      that behavioral responses to phenol, and perhaps to temperature, cytoplasmic pH,
      and glycerol, as well, occur through a general sensing mechanism in
      chemoreceptors that detects changes in the structural stability or dynamic
      behavior of a receptor signaling element. The structurally sensitive target for
      phenol is probably the TM bundle, but other behaviors could target other receptor
      elements.

PMID- 21965562
TI  - Mutational analysis of N381, a key trimer contact residue in Tsr, the Escherichia
      coli serine chemoreceptor.
AB  - Chemoreceptors such as Tsr, the serine receptor, function in trimer-of-dimer
      associations to mediate chemotactic behavior in Escherichia coli. The two
      subunits of each receptor homodimer occupy different positions in the trimer, one
      at its central axis and the other at the trimer periphery. Residue N381 of Tsr
      contributes to trimer stability through interactions with its counterparts in a
      central cavity surrounded by hydrophobic residues at the trimer axis. To assess
      the functional role of N381, we created and characterized a full set of amino
      acid replacements at this Tsr residue. We found that every amino acid replacement
      at N381 destroyed Tsr function, and all but one (N381G) of the mutant receptors
      also blocked signaling by Tar, the aspartate chemoreceptor. Tar jamming reflects
      the formation of signaling-defective mixed trimers of dimers, and in vivo assays
      with a trifunctional cross-linking reagent demonstrated trimer-based interactions
      between Tar and Tsr-N381 mutants. Mutant Tsr molecules with a charged amino acid
      or proline replacement exhibited the most severe trimer formation defects. These
      trimer-defective receptors, as well as most of the trimer-competent mutant
      receptors, were unable to form ternary signaling complexes with the CheA kinase
      and with CheW, which couples CheA to receptor control. Some of the trimer
      competent mutant receptors, particularly those with a hydrophobic amino acid
      replacement, may not bind CheW/CheA because they form conformationally frozen or
      distorted trimers. These findings indicate that trimer dynamics probably are
      important for ternary complex assembly and that N381 may not be a direct binding
      determinant for CheW/CheA at the trimer periphery.

PMID- 21965563
TI  - FtsH-dependent degradation of phage shock protein C in Yersinia enterocolitica
      and Escherichia coli.
AB  - The widely conserved phage shock protein (Psp) extracytoplasmic stress response
      has been studied extensively in Escherichia coli and Yersinia enterocolitica.
      Both species have the PspF, -A, -B, and -C proteins, which have been linked to
      robust phenotypes, including Y. enterocolitica virulence. PspB and PspC are
      cytoplasmic membrane proteins required for stress-dependent induction of psp gene
      expression and for bacterial survival during the mislocalization of outer
      membrane secretin proteins. Previously, we reported that Y. enterocolitica PspB
      functions to positively control the amount of PspC by an uncharacterized
      posttranscriptional mechanism. In this study, we have discovered that the
      cytoplasmic membrane protease FtsH is involved in this phenomenon. FtsH
      destabilizes PspC in Y. enterocolitica, but coproduction of PspC with its binding
      partner PspB was sufficient to prevent this destabilization. In contrast, FtsH
      did not affect any other core component of the Psp system. These data suggested
      that uncomplexed PspC might be particularly deleterious to the bacterial cell and
      that FtsH acts as an important quality control mechanism to remove it. This was
      supported by the observation that toxicity caused by PspC production was reduced
      either by coproduction of PspB or by increased synthesis of FtsH. We also found
      that the phenomenon of FtsH-dependent PspC destabilization is conserved between
      Y. enterocolitica and E. coli.

PMID- 21965564
TI  - Hopanoid production is required for low-pH tolerance, antimicrobial resistance,
      and motility in Burkholderia cenocepacia.
AB  - Hopanoids are pentacyclic triterpenoids that are thought to be bacterial
      surrogates for eukaryotic sterols, such as cholesterol, acting to stabilize
      membranes and to regulate their fluidity and permeability. To date, very few
      studies have evaluated the role of hopanoids in bacterial physiology. The
      synthesis of hopanoids depends on the enzyme squalene-hopene cyclase (Shc), which
      converts the linear squalene into the basic hopene structure. Deletion of the 2
      genes encoding Shc enzymes in Burkholderia cenocepacia K56-2, BCAM2831 and
      BCAS0167, resulted in a strain that was unable to produce hopanoids, as
      demonstrated by gas chromatography and mass spectrometry. Complementation of the
      Deltashc mutant with only BCAM2831 was sufficient to restore hopanoid production
      to wild-type levels, while introducing a copy of BCAS0167 alone into the Deltashc
      mutant produced only very small amounts of the hopanoid peak. The Deltashc mutant
      grew as well as the wild type in medium buffered to pH 7 and demonstrated no
      defect in its ability to survive and replicate within macrophages, despite
      transmission electron microscopy (TEM) revealing defects in the organization of
      the cell envelope. The Deltashc mutant displayed increased sensitivity to low pH,
      detergent, and various antibiotics, including polymyxin B and erythromycin. Loss
      of hopanoid production also resulted in severe defects in both swimming and
      swarming motility. This suggests that hopanoid production plays an important role
      in the physiology of B. cenocepacia.

PMID- 21965565
TI  - A Chlamydia-specific C-terminal region of the stress response regulator HrcA
      modulates its repressor activity.
AB  - Chlamydial heat shock proteins have important roles in Chlamydia infection and
      immunopathogenesis. Transcription of chlamydial heat shock genes is controlled by
      the stress response regulator HrcA, which binds to its cognate operator CIRCE,
      causing repression by steric hindrance of RNA polymerase. All Chlamydia spp.
      encode an HrcA protein that is larger than other bacterial orthologs because of
      an additional, well-conserved C-terminal region. We found that this unique C
      terminal tail decreased HrcA binding to CIRCE in vitro as well as HrcA-mediated
      transcriptional repression in vitro and in vivo. When we isolated HrcA from
      chlamydiae, we only detected the full-length protein, but we found that
      endogenous HrcA had a higher binding affinity for CIRCE than recombinant HrcA. To
      examine this difference further, we tested the effect of the heat shock protein
      GroEL on the function of HrcA since endogenous chlamydial HrcA has been
      previously shown to associate with GroEL as a complex. GroEL enhanced the ability
      of HrcA to bind CIRCE and to repress transcription in vitro, but this stimulatory
      effect was greater on full-length HrcA than HrcA lacking the C-terminal tail.
      These findings demonstrate that the novel C-terminal tail of chlamydial HrcA is
      an inhibitory region and provide evidence that its negative effect on repressor
      function can be counteracted by GroEL. These results support a model in which
      GroEL functions as a corepressor that interacts with HrcA to regulate chlamydial
      heat shock genes.

PMID- 21965566
TI  - Regulation of transcription by SMU.1349, a TetR family regulator, in
      Streptococcus mutans.
AB  - The TetR family of transcriptional regulators is ubiquitous in bacteria, where it
      plays an important role in bacterial gene expression. Streptococcus mutans, a
      gram-positive pathogen considered to be the primary etiological agent in the
      formation of dental caries, encodes at least 18 TetR regulators. Here we
      characterized one such TetR regulator, SMU.1349, encoded by the TnSmu2 operon,
      which appeared to be acquired by the organism via horizontal gene transfer.
      SMU.1349 is transcribed divergently from the rest of the genes encoded by the
      operon. By the use of a transcriptional reporter system and semiquantitative
      reverse transcription-PCR (RT-PCR), we demonstrated that SMU.1349 activates the
      transcription of several genes that are encoded within the TnSmu2 operon. Gel
      mobility shift and DNase I footprinting assays with purified SMU.1349 protein
      demonstrated binding to the intergenic region between SMU.1349 and the TnSmu2
      operon; therefore, SMU.1349 is directly involved in gene transcription. Using
      purified S. mutans RpoD and Escherichia coli RNA polymerase, we also demonstrated
      in an in vitro transcription assay that SMU.1349 could activate transcription
      from the TnSmu2 operon promoter. Furthermore, we showed that SMU.1349 could also
      repress transcription from its own promoter by binding to the intergenic region,
      suggesting that SMU.1349 acts as both an activator and a repressor. Thus, unlike
      most of the TetR family proteins, which generally function as transcriptional
      repressors, SMU.1349 is unique in that it can function as both.

PMID- 21965567
TI  - 2-Heptyl-4-quinolone, a precursor of the Pseudomonas quinolone signal molecule,
      modulates swarming motility in Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen capable of group behaviors,
      including biofilm formation and swarming motility. These group behaviors are
      regulated by both the intracellular signaling molecule c-di-GMP and
      acylhomoserine lactone quorum-sensing systems. Here, we show that the Pseudomonas
      quinolone signal (PQS) system also contributes to the regulation of swarming
      motility. Specifically, our data indicate that 2-heptyl-4-quinolone (HHQ), a
      precursor of PQS, likely induces the production of the phenazine-1-carboxylic
      acid (PCA), which in turn acts via an as-yet-unknown downstream mechanism to
      repress swarming motility. We show that this HHQ- and PCA-dependent swarming
      repression is apparently independent of changes in global levels of c-di-GMP,
      suggesting complex regulation of this group behavior.

PMID- 21965568
TI  - Cyclohexane-1,2-dione hydrolase from denitrifying Azoarcus sp. strain 22Lin, a
      novel member of the thiamine diphosphate enzyme family.
AB  - Alicyclic compounds with hydroxyl groups represent common structures in numerous
      natural compounds, such as terpenes and steroids. Their degradation by
      microorganisms in the absence of dioxygen may involve a C-C bond ring cleavage to
      form an aliphatic intermediate that can be further oxidized. The cyclohexane-1,2
      dione hydrolase (CDH) (EC 3.7.1.11) from denitrifying Azoarcus sp. strain 22Lin,
      grown on cyclohexane-1,2-diol as a sole electron donor and carbon source, is the
      first thiamine diphosphate (ThDP)-dependent enzyme characterized to date that
      cleaves a cyclic aliphatic compound. The degradation of cyclohexane-1,2-dione
      (CDO) to 6-oxohexanoate comprises the cleavage of a C-C bond adjacent to a
      carbonyl group, a typical feature of reactions catalyzed by ThDP-dependent
      enzymes. In the subsequent NAD(+)-dependent reaction, 6-oxohexanoate is oxidized
      to adipate. CDH has been purified to homogeneity by the criteria of gel
      electrophoresis (a single band at ~59 kDa; calculated molecular mass, 64.5 kDa);
      in solution, the enzyme is a homodimer (~105 kDa; gel filtration). As isolated,
      CDH contains 0.8 +/- 0.05 ThDP, 1.0 +/- 0.02 Mg(2+), and 1.0 +/- 0.015 flavin
      adenine dinucleotide (FAD) per monomer as a second organic cofactor, the role of
      which remains unclear. Strong reductants, Ti(III)-citrate, Na(+)-dithionite, and
      the photochemical 5-deazaflavin/oxalate system, led to a partial reduction of the
      FAD chromophore. The cleavage product of CDO, 6-oxohexanoate, was also a
      substrate; the corresponding cyclic 1,3- and 1,4-diones did not react with CDH,
      nor did the cis- and trans-cyclohexane diols. The enzymes acetohydroxyacid
      synthase (AHAS) from Saccharomyces cerevisiae, pyruvate oxidase (POX) from
      Lactobacillus plantarum, benzoylformate decarboxylase from Pseudomonas putida,
      and pyruvate decarboxylase from Zymomonas mobilis were identified as the closest
      relatives of CDH by comparative amino acid sequence analysis, and a ThDP binding
      motif and a 2-fold Rossmann fold for FAD binding could be localized at the C
      terminal end and central region of CDH, respectively. A first mechanism for the
      ring cleavage of CDO is presented, and it is suggested that the FAD cofactor in
      CDH is an evolutionary relict.

PMID- 21965569
TI  - Probing the Borrelia burgdorferi surface lipoprotein secretion pathway using a
      conditionally folding protein domain.
AB  - Surface lipoproteins of Borrelia spirochetes are important virulence determinants
      in the transmission and pathogenesis of Lyme disease and relapsing fever. To
      further define the conformational secretion requirements and to identify
      potential lipoprotein translocation intermediates associated with the bacterial
      outer membrane (OM), we generated constructs in which Borrelia burgdorferi outer
      surface lipoprotein A (OspA) was fused to calmodulin (CaM), a conserved
      eukaryotic protein undergoing calcium-dependent folding. Protein localization
      assays showed that constructs in which CaM was fused to full-length wild-type
      (wt) OspA or to an intact OspA N-terminal "tether" peptide retained their
      competence for OM translocation even in the presence of calcium. In contrast,
      constructs in which CaM was fused to truncated or mutant OspA N-terminal tether
      peptides were targeted to the periplasmic leaflet of the OM in the presence of
      calcium but could be flipped to the bacterial surface upon calcium chelation.
      This indicated that in the absence of an intact tether peptide, unfolding of the
      CaM moiety was required in order to facilitate OM traversal. Together, these data
      further support a periplasmic tether peptide-mediated mechanism to prevent
      premature folding of B. burgdorferi surface lipoproteins. The specific shift in
      the OM topology of sequence-identical lipopeptides due to a single-variable
      change in environmental conditions also indicates that surface-bound Borrelia
      lipoproteins can localize transiently to the periplasmic leaflet of the OM.

PMID- 21965570
TI  - Impact of the N-terminal secretor domain on YopD translocator function in
      Yersinia pseudotuberculosis type III secretion.
AB  - Type III secretion systems (T3SSs) secrete needle components, pore-forming
      translocators, and the translocated effectors. In part, effector recognition by a
      T3SS involves their N-terminal amino acids and their 5' mRNA. To investigate
      whether similar molecular constraints influence translocator secretion, we
      scrutinized this region within YopD from Yersinia pseudotuberculosis. Mutations
      in the 5' end of yopD that resulted in specific disruption of the mRNA sequence
      did not affect YopD secretion. On the other hand, a few mutations affecting the
      protein sequence reduced secretion. Translational reporter fusions identified the
      first five codons as a minimal N-terminal secretion signal and also indicated
      that the YopD N terminus might be important for yopD translation control. Hybrid
      proteins in which the N terminus of YopD was exchanged with the equivalent region
      of the YopE effector or the YopB translocator were also constructed. While the in
      vitro secretion profile was unaltered, these modified bacteria were all
      compromised with respect to T3SS activity in the presence of immune cells. Thus,
      the YopD N terminus does harbor a secretion signal that may also incorporate
      mechanisms of yopD translation control. This signal tolerates a high degree of
      variation while still maintaining secretion competence suggestive of inherent
      structural peculiarities that make it distinct from secretion signals of other
      T3SS substrates.

PMID- 21965571
TI  - Positive regulation of the Vibrio cholerae porin OmpT by iron and fur.
AB  - The transcription factor Fur regulates the expression of a number of genes in
      Vibrio cholerae in response to changes in the level of available iron. Fur
      usually acts as a repressor, but here we show that Fur positively regulates the
      expression of ompT, which encodes a major outer membrane porin. OmpT levels
      increased when the bacteria were grown in medium containing relatively high
      levels of iron, and this effect required Fur. The level of ompT mRNA also is
      increased in the presence of iron and Fur. The effect of iron on OmpT levels was
      independent of the known ompT regulators ToxR and Crp, and it did not require
      RyhB, which has been shown to be responsible for positive regulation by iron of
      some V. cholerae genes. Electrophoretic mobility shift assays showed that Fur
      binds upstream of the ompT transcription start site in a region overlapping known
      binding sites for ToxR and Crp. These data suggest that Fur and iron positively
      regulate ompT expression through the direct binding of Fur to the ompT promoter.

PMID- 21965572
TI  - Regulation of biofilm components in Salmonella enterica serovar Typhimurium by
      lytic transglycosylases involved in cell wall turnover.
AB  - In Salmonella enterica serovar Typhimurium, a biofilm mode of growth known as the
      rdar morphotype is regulated by several networks which sense multiple
      environmental signals. The transcriptional regulator CsgD is the major target for
      these regulatory pathways. In this study, we show that two lytic
      transglycosylases of family I, MltE and MltC, in combination increase CsgD
      expression and rdar morphotype. MltE and MltC, which share a highly similar
      transglycosylase SLT domain, work redundantly to regulate CsgD at the
      transcriptional and posttranscriptional levels. The effect of MltE and MltC on
      CsgD levels was independent of the known regulatory pathways that sense cell
      envelope stress. These findings reveal, for the first time, a specific function
      of lytic transglycosylases in S. Typhimurium and suggest the existence of a new
      signaling pathway that links cell wall turnover to biofilm formation.

PMID- 21965574
TI  - YcdY protein of Escherichia coli, an atypical member of the TorD chaperone
      family.
AB  - The TorD family of specific chaperones is divided into four subfamilies dedicated
      to molybdoenzyme biogenesis and a fifth one, exemplified by YcdY of Escherichia
      coli, for which no defined partner has been identified so far. We propose that
      YcdY is the chaperone of YcdX, a zinc protein involved in the swarming motility
      process of E. coli, since YcdY interacts with YcdX and increases its activity in
      vitro.

PMID- 21965573
TI  - Interplay among cyclic diguanylate, HapR, and the general stress response
      regulator (RpoS) in the regulation of Vibrio cholerae hemagglutinin/protease.
AB  - Vibrio cholerae secretes the Zn-dependent metalloprotease hemagglutinin
      (HA)/protease (mucinase), which is encoded by hapA and displays a broad range of
      potential pathogenic activities. Expression of HA/protease has a stringent
      requirement for the quorum-sensing regulator HapR and the general stress response
      regulator RpoS. Here we report that the second messenger cyclic diguanylic acid
      (c-di-GMP) regulates the production of HA/protease in a negative manner.
      Overexpression of a diguanylate cyclase to increase the cellular c-di-GMP pool
      resulted in diminished expression of HA/protease and its positive regulator,
      HapR. The effect of c-di-GMP on HapR was independent of LuxO but was abolished by
      deletion of the c-di-GMP binding protein VpsT, the LuxR-type regulator VqmA, or a
      single-base mutation in the hapR promoter that prevents autorepression. Though
      expression of HapR had a positive effect on RpoS biosynthesis, direct
      manipulation of the c-di-GMP pool at a high cell density did not significantly
      impact RpoS expression in the wild-type genetic background. In contrast,
      increasing the c-di-GMP pool severely inhibited RpoS expression in a DeltahapR
      mutant that is locked in a regulatory state mimicking low cell density. Based on
      the above findings, we propose a model for the interplay between HapR, RpoS, and
      c-di-GMP in the regulation of HA/protease expression.

PMID- 21965575
TI  - Ultrastructural analysis and identification of envelope proteins of "Candidatus
      Chloracidobacterium thermophilum" chlorosomes.
AB  - Chlorosomes are sac-like, light-harvesting organelles that characteristically
      contain very large numbers of bacteriochlorophyll (BChl) c, d, or e molecules.
      These antenna structures occur in chlorophototrophs belonging to some members of
      the Chlorobi and Chloroflexi phyla and are also found in a recently discovered
      member of the phylum Acidobacteria, "Candidatus Chloracidobacterium
      thermophilum." "Ca. Chloracidobacterium thermophilum" is the first aerobic
      organism discovered to possess chlorosomes as light-harvesting antennae for
      phototrophic growth. Chlorosomes were isolated from "Ca. Chloracidobacterium
      thermophilum" and subjected to electron microscopic, spectroscopic, and
      biochemical analyses. The chlorosomes of "Ca. Chloracidobacterium thermophilum"
      had an average size of ~100 by 30 nm. Cryo-electron microscopy showed that the
      BChl c molecules formed folded or twisted, sheet-like structures with a lamellar
      spacing of ~2.3 nm. Unlike the BChls in the chlorosomes of the green sulfur
      bacterium Chlorobaculum tepidum, concentric cylindrical nanotubes were not
      observed. Chlorosomes of "Ca. Chloracidobacterium thermophilum" contained a
      homolog of CsmA, the BChl a-binding, baseplate protein; CsmV, a protein distantly
      related to CsmI, CsmJ, and CsmX of C. tepidum, which probably binds a single [2Fe
      2S] cluster; and five unique polypeptides (CsmR, CsmS, CsmT, CsmU, and a type II
      NADH dehydrogenase homolog). Although "Ca. Chloracidobacterium thermophilum" is
      an aerobe, energy transfer among the BChls in these chlorosomes was very strongly
      quenched in the presence of oxygen (as measured by quenching of fluorescence
      emission). The combined analyses showed that the chlorosomes of "Ca.
      Chloracidobacterium thermophilum" possess a number of unique features but also
      share some properties with the chlorosomes found in anaerobic members of other
      phyla.

PMID- 21965576
TI  - Canonical SecA associates with an accessory secretory protein complex involved in
      biogenesis of a streptococcal serine-rich repeat glycoprotein.
AB  - Fap1, a serine-rich repeat glycoprotein (SRRP), is required for bacterial biofilm
      formation of Streptococcus parasanguinis. Fap1-like SRRPs are found in many gram
      positive bacteria and have been implicated in bacterial fitness and virulence. A
      conserved five-gene cluster, secY2-gap1-gap2-gap3-secA2, located immediately
      downstream of fap1, is required for Fap1 biogenesis. secA2, gap1, and gap3 encode
      three putative accessory Sec proteins. SecA2 mediates export of mature Fap1, and
      Gap1 and Gap3 are required for Fap1 biogenesis. Interestingly, gap1 and gap3
      mutants exhibited the same phenotype as a secA2 mutant, implying that Gap1 and
      Gap3 may interact with SecA2 to mediate Fap1 biogenesis. Glutathione S
      transferase pulldown experiments revealed a direct interaction between SecA2,
      Gap1, and Gap3 in vitro. Coimmunoprecipitation analysis demonstrated the
      formation of a SecA2-Gap1-Gap3 complex. Homologues of SecA2, Gap1, and Gap3 are
      conserved in many streptococci and staphylococci. The corresponding homologues
      from Streptococcus agalactiae also interacted with each other and formed a
      protein complex. Furthermore, the Gap1 homologues from S. agalactiae and
      Streptococcus sanguinis rescued the Fap1 defect in the Gap1 mutant, indicating
      the functional conservation of the accessory Sec complex. Importantly, canonical
      SecA interacted with the accessory Sec protein complex, suggesting that the
      biogenesis of SRRPs mediated by the accessory Sec system is linked to the
      canonical Sec system.

PMID- 21965577
TI  - KynR, a Lrp/AsnC-type transcriptional regulator, directly controls the kynurenine
      pathway in Pseudomonas aeruginosa.
AB  - The opportunistic pathogen Pseudomonas aeruginosa can utilize a variety of carbon
      sources and produces many secondary metabolites to help survive harsh
      environments. P. aeruginosa is part of a small group of bacteria that use the
      kynurenine pathway to catabolize tryptophan. Through the kynurenine pathway,
      tryptophan is broken down into anthranilate, which is further degraded into
      tricarboxylic acid cycle intermediates or utilized to make numerous aromatic
      compounds, including the Pseudomonas quinolone signal (PQS). We have previously
      shown that the kynurenine pathway is a critical source of anthranilate for PQS
      synthesis and that the kynurenine pathway genes (kynA and kynBU) are upregulated
      in the presence of kynurenine. A putative Lrp/AsnC-type transcriptional regulator
      (gene PA2082, here called kynR), is divergently transcribed from the kynBU operon
      and is highly conserved in gram-negative bacteria that harbor the kynurenine
      pathway. We show that a mutation in kynR renders P. aeruginosa unable to utilize
      L-tryptophan as a sole carbon source and decreases PQS production. In addition,
      we found that the increase of kynA and kynB transcriptional activity in response
      to kynurenine was completely abolished in a kynR mutant, further indicating that
      KynR mediates the kynurenine-dependent expression of the kynurenine pathway
      genes. Finally, we found that purified KynR specifically bound the kynA promoter
      in the presence of kynurenine and bound the kynB promoter in the absence or
      presence of kynurenine. Taken together, our data show that KynR directly
      regulates the kynurenine pathway genes.

PMID- 21965578
TI  - Onychomatricoma: a case report with literature review.
AB  - Onychomatricoma (OM) is a fibroepithelial tumor of nail matrix that occurs in the
      digits of both the hands and feet. This was first reported by Baran and Kint.
      They initially described 3 cases, all of which demonstrated a filamentous tumor
      of matrix tissue that resulted in a thickened funnel-shaped nail. Although
      apparently benign, it is subject to recurrence, and long-term follow-up is
      recommended because it is not known whether there is a conversion to malignancy.
      Even though this neoplasm was first described more than 18 years ago, there
      remains a dearth of case reports (currently fewer than 50) in the literature.
      This is a single case report and literature review. Levels of Evidence :
      Therapeutic, Level IV.

PMID- 21965579
TI  - Efficacy of intravenous tissue plasminogen activator in frostbite patients and
      presentation of a treatment protocol for frostbite patients.
AB  - Frostbite can be a devastating and even debilitating injury. Early identification
      and proper treatment of frostbite is critical in saving digits and limbs. Tissue
      plasminogen activator (tPA) has been shown to be effective in reducing the number
      of digits amputated after severe frostbite injury. Nothing has been presented in
      the podiatric literature regarding the use of tPA in treating frostbite patients
      for preserving toes and feet. Intravenous tPA and IV heparin were used to treat
      severe frostbite injuries that did not show improvement after rapid rewarming,
      had absent Doppler pulses in the distal limb or digits, showed limited or no
      perfusion by Tc-99 3-phase bone scan, and had no contraindications to use of tPA.
      All 11 patients included in this study were treated at Hennepin County Medical
      Center between 2008 and 2010. A total of 73 digits (upper and lower extremity)
      were considered at risk for amputation after evaluation with Tc-99 bone scan. Of
      those digits that were affected, 43 were amputated. Intravenous tPA is a safe and
      effective treatment to reduce the number of digital amputations after severe
      frostbite injury. The authors' protocol for treating severe frostbite includes
      the use of tPA. LEVELS OF EVIDENCE: Therapeutic, Level IV.

PMID- 21965580
TI  - A case report of fibular aplasia, tibial campomelia, and oligosyndactyly (FATCO)
      syndrome associated with Klinefelter syndrome and review of the literature.
AB  - Limb development is a complex regulated development phenomenon involving multiple
      genes. Fibular Aplasia, Tibial Campomelia and Oligosyndactyly (FATCO) syndrome
      (MIM#246570) is a syndrome of unknown genetic basis and inheritance with variable
      expressivity and penetrance. Its counterpart, Fuhrmann syndrome or Femoral
      Fibularaplasia-Campomelia and Oligosyndactyly are a result of defect in the WNT7a
      gene located on the 3p25. Former is proposed to be a development dysplasia of
      defective dorso-ventral polarity assignment and distal limb development.
      Ectrodactyly and fibular a/hypoplasia (EFA, MIM# 113310) share the full
      phenotypic spectrum of FATCO syndrome, whether they are allelic disorders or
      represent two variable presentations in the spectrum of the same disorder is not
      an established fact. We report here one Indian patient with findings of FATCO
      syndrome with associated Klinefelter syndrome. This is the first such report
      which is likely to be a co-incidental finding and has implications for genetic
      counseling. LEVELS OF EVIDENCE: Therapeutic, Level IV.

PMID- 21965581
TI  - Osteoarthritis of the ankle and foot complex in former Greek soccer players.
AB  - Sports activities cause increased loads in elite athletes' joints. Current
      scientific knowledge highlights the importance of applied mechanical loads on the
      physiology and pathophysiology of the articular cartilage. Thus, it is possible
      that sporting activity has a role in the development of osteoarthritis (OA), a
      painful and damaging joint disease. The aim of the present study was to
      investigate and record osteoarthritic alterations in the ankle and foot complex
      in former Greek soccer players and also compare them with those in the general
      population. The study sample consisted of 170 male, former elite soccer players,
      aged between 42 and 55 years (mean = 49.8 years, standard deviation [SD] = 7.4).
      A control group of 132 men, aged between 42 and 55 years (mean, 50.7 years, SD =
      9.9), with no regular athletic activity were examined. The development of
      osteoarthritic alterations was recorded through a questionnaire and clinical and
      radiological examination. Radiographic analysis of the images in former athletes
      group showed not only more signs of cartilage degeneration in comparison with the
      control group (P < .05) but also similar clinical manifestations (pain and
      impaired mobility; P > .05). Osteophyte formation is a frequent disease among
      former soccer players--with variations on radiographic images--but it does not
      appear in their clinical picture. However, it is likely that both spurs and
      subchondral sclerosis (main findings) are preclinical manifestations of OA.
      LEVELS OF EVIDENCE: Prognostic, Level II.

PMID- 21965582
TI  - A method used to access the functional outcome of tibial posterior tendon
      transfer for foot drop in leprosy.
AB  - OBJECTIVES: The aim of this study was to access the postoperative functional
      results of posterior tibial tendon transfer for foot drop as a consequence of
      nerve palsy in leprosy. MATERIAL AND METHODS: Thirteen patients (9 males and 4
      females) with ages ranging from 9 to 69 years were submitted to posterior tibial
      tendon transfer by the circumtibial route to correct foot drop in leprosy. The
      length of postoperative follow-up ranged from 1 to 5 years. The Stanmore system
      was used as a method for evaluating the functional results of postoperative
      posterior tibial tendon transfer. This system is made up of 7 different
      categories and the total score is 100. RESULTS: According to the Stanmore system,
      the results were poor in 1 patient (7.6%), moderate in 2 feet (15.3%), good in 5
      feet (38.4%), and excellent in 5 feet (38.4%). All the patients were satisfied
      with the final outcome. CONCLUSION: The posterior tibial tendon transfer for foot
      drop in leprosy was efficient in restoring normal function of the foot and gait
      without changing foot posture. In the absence of a standardized method for
      assessing the results of posterior tibial tendon transfer, the Stanmore system
      seems to be a good tool for an objective evaluation.

PMID- 21965583
TI  - Pharmacological modulation of peritoneal injury induced by dialysis fluids: is it
      an option?

PMID- 21965584
TI  - A red herring in vascular calcification: 'nanobacteria' are protein-mineral
      complexes involved in biomineralization.
AB  - Biomineralization at pathological extraosseous sites (i.e. vasculature and soft
      tissues) is associated with increased morbidity and mortality. So-called
      'nanobacteria' have been described as pathogenic agents causing many diseases
      including calcification. Initially, their appearance, and having a content
      consisting of nucleic acids plus proteins and properties of growing structures,
      suggested that they were living organisms. However, it could be demonstrated that
      the so-called nanobacteria were in fact mineralizing nanoparticles that contain
      mineral and non-mineral compounds, that these particles bind to charged molecules
      and that supersaturation enables in vitro growth of these nanoparticles. Recent
      data indicate that nanoparticles consisting of protein-mineral complexes can be
      seen both in vitro and in vivo as precursors of matrix calcification.

PMID- 21965585
TI  - Stimulation of the PD-1/PDL-1 T-cell co-inhibitory pathway is effective in
      treatment of experimental autoimmune glomerulonephritis.
AB  - BACKGROUND: Experimental autoimmune glomerulonephritis (EAG) can be induced in
      Wistar-Kyoto (WKY) rats by immunization with the recombinant NC1 domain of the
      alpha 3 chain of type IV collagen [alpha3(IV)NC1]. EAG is characterized by
      circulating and deposited anti-alpha3(IV)NC1 antibodies, accompanied by focal
      necrotizing glomerulonephritis with crescent formation. Programmed death-1 (PD-1)
      receptor is preferentially expressed on activated T cells and binds two known
      ligands present on antigen presenting cells, PDL-1 and PDL-2. Engagement of PD-1
      by its ligands results in a negative regulatory effect, with inhibition of
      downstream cellular signalling events and diminished cellular proliferation.
      METHODS: In order to investigate the role of the PD-1/PDL-1 co-inhibitory pathway
      in development of EAG, the in vivo effects of a stimulating PDL-1/Fc fusion
      protein were examined after the onset of disease. RESULTS: Stimulation of PD-1
      led to a significant reduction in albuminuria, serum urea, serum creatinine,
      crescent formation and tubular damage compared with controls. There was also a
      reduction in numbers of glomerular macrophages, CD4+ T cells, CD8+ T cells and
      PD1+ cells compared with controls. No reduction was observed in levels of
      circulating or deposited antibodies. CONCLUSIONS: These results demonstrate that
      PDL-1/Fc fusion protein is effective in treatment of glomerulonephritis and
      confirm the importance of the PD-1/PDL-1 T-cell co-inhibitory pathway in
      development of EAG. Strategies designed to stimulate this pathway may provide a
      novel approach to treatment of human glomerulonephritis.

PMID- 21965586
TI  - Long-term renal survival and related risk factors in patients with IgA
      nephropathy: results from a cohort of 1155 cases in a Chinese adult population.
AB  - BACKGROUND: We sought to identify the long-term renal survival rate and related
      risk factors of progression to renal failure in Chinese adult patients with IgA
      nephropathy (IgAN) and to quantify the effects of proteinuria during the follow
      up on outcome in patients with IgAN. METHODS: Patients with biopsy-proven primary
      IgAN in the Nanjing Glomerulonephritis Registry were studied. Renal survival and
      the relationships between clinical parameters and renal outcomes were assessed.
      RESULTS: One thousand one hundred and fifty-five patients were enrolled in this
      study. The 10-, 15- and 20-year cumulative renal survival rates, calculated by
      Kaplan-Meier method, were 83, 74 and 64%, respectively. At the time of biopsy,
      proteinuria>1.0 g/day [hazard ratio (HR) 3.2, P<0.001], estimated glomerular
      filtration rate (eGFR)<60 mL/min/1.73 m2 (HR 2.6, P<0.001), hypertension (HR 1.9,
      P<0.001), hypoproteinemia (HR 2.0, P<0.001) and hyperuricemia (HR 2.1, P<0.001)
      were the independent risk factors. Multivariate Cox analysis showed the time
      average proteinuria (TA-P) during follow-up was the most important risk factor of
      renal failure. Patients with TA-P>1.0 g/day were associated with a 9.4-fold risk
      than patients with TA-P<1.0 g/day (P<0.001) and 46.5-fold risk than those with TA
      P<0.5 g/day (P<0.001). Moreover, patients who achieved TA-P<0.5 g/day benefit
      much more than those with TA-P between 0.5 and 1.0 g/day (HR 13.1, P<0.001).
      CONCLUSIONS: Thirty-six percent of Chinese adult patients with IgAN progress to
      end stage renal disease within 20 years. Five clinical features-higher
      proteinuria, hypertension, impaired renal function, hypoproteinemia and
      hyperuricemia-are independent predictors of an unfavorable renal outcome. The
      basic goal of anti-proteinuric therapy for Chinese patients is to lower
      proteinuria<1.0 g/day and the optimal goal is to lower proteinuria to <0.5 g/day.

PMID- 21965587
TI  - Malignant hypertension secondary to renovascular disease during infancy--an
      unusual cause of failure to thrive.
AB  - An 11-month-old girl presented with a history of failure to thrive, vomiting,
      polydipsia, polyuria and visual inattention. She was found to have malignant
      hypertension due to unilateral renal artery stenosis. This was successfully
      treated with percutaneous transluminal balloon angioplasty. Nearly 10 years
      following this initial presentation, she remains normotensive on no anti
      hypertensive medications.

PMID- 21965588
TI  - Amanita poisonings resulting in acute, reversible renal failure: new cases, new
      toxic Amanita mushrooms.
AB  - BACKGROUND: Renal failure as a consequence of eating mushrooms has been reported
      repeatedly after ingestion of webcaps of the Cortinarius orellanus group. But
      mushrooms of the genus Amanita can also cause renal failure: Amanita smithiana
      (North America) and Amanita proxima (Mediterranean area). Here, we discuss
      poisonings caused by other white amanitas. A German and--independently--two
      Portuguese patients reported the ingestion of completely white mushrooms with
      ring. Similar to intoxications with A. smithiana or A. proxima, the clinical
      picture was characterized by nausea and vomiting 10-12 h after ingestion, severe
      acute renal failure and mild hepatitis. Renal biopsy showed acute interstitial
      nephritis and tubular necrosis. Two patients were given temporary haemodialysis.
      All have fully recovered their renal function. Poisonings caused by mushrooms
      containing the toxin of A. smithiana were suspected. We tested 20 Amanita species
      for the presence of this toxin. METHODS: Thin layer chromatography was applied to
      detect A. smithiana nephrotoxin in herbarium specimens using authentic material
      of A. smithiana as reference. RESULTS: A. smithiana toxin could be detected in
      Amanita boudieri, Amanita gracilior and in Amanita echinocephala. A. boudieri was
      collected by the Portuguese patients. A. echinocephala is the only nephrotoxic
      Amanita growing North of the Alps and is suspected to be the cause of renal
      failure in the German patient. No A. smithiana toxin was detectable in the
      nephrotoxic A. proxima. CONCLUSIONS: A. boudieri, A. gracilior and A.
      echinocephala are nephrotoxic. These intoxications are clinically similar to that
      of A. smithiana, with acute reversible renal failure and mild hepatitis but are
      different in their clinical picture from Orellanus syndrome characterized by a
      delayed onset of severe and often irreversible renal failure.

PMID- 21965589
TI  - Association of anthropometric obesity measures with chronic kidney disease risk
      in a non-diabetic patient population.
AB  - BACKGROUND: Obesity is a risk factor for both chronic kidney disease (CKD) and
      cardiovascular disease. The association of simple indices of obesity with CKD
      remains poorly understood. Evidence suggests that measures of central obesity
      such as waist circumference (WC) and waist-to-hip ratio (WHR) are more accurate
      predictors of morbidity and cardiovascular risk than body mass index (BMI). This
      study aimed to investigate the association of BMI, WC and WHR with CKD risk in a
      population screened for type 2 diabetes. METHODS: Data were drawn from a
      population-based screening programme of 6475 volunteers without pre-existing
      diabetes. A number of investigations and cardiovascular health-related
      assessments were performed. Participants were categorized into two groups: those
      with an estimated glomerular filtration rate (eGFR) >=60 and <60 mL/min/1.73m(2).
      Participants were also categorized as low, medium and high risk according to each
      anthropometric variable. RESULTS: CKD was independently associated with higher WC
      and BMI (P < 0.01) but not WHR (P = 0.47). Increasing obesity measured by BMI and
      WC was associated with a reduction in eGFR for both men and women (P < 0.001).
      Increasing risk categories for BMI and WC were also associated with lower eGFR in
      men and women (P < 0.001). Combining anthropometric measures provided no
      additional measure of risk for underlying CKD. CONCLUSIONS: WC may be a simple
      and reliable clinical tool for the detection of underlying CKD within primary
      care. Given the complex interaction between adiposity and uraemia, a combined
      screening tool using BMI and WC or WHR is unlikely to provide any additional
      benefit to risk analysis.

PMID- 21965590
TI  - Teaching and training acute renal replacement therapy in children.
AB  - BACKGROUND: The objective of this study is to describe and analyse the initial
      experience in paediatric acute renal replacement therapy (ARRT) education by
      means of specific courses. METHODS: Three paediatric ARRT courses were run. The
      course programme included initial and final multiple-choice question (MCQ) exams,
      short lectures, practical workshops [in vitro peritoneal dialysis (PD) and
      continuous renal replacement therapy (CRRT) machines skill stations, real-time PD
      and CRRT in paediatric animal models and paediatric CRRT advanced simulation
      scenarios based on real cases) and an anonymous survey on the perceived value of
      the course (score from 0: very bad to 10: perfect). Number of students per
      workshop was six to eight. Continuous assessment of participants' performance was
      done. RESULTS: In the initial MCQ, only 11% of students answered correctly at
      least 70% of questions, while in the final test, 90.5% hit this target (P <
      0.001). In the performance assessments, all of the students demonstrated
      sufficient acquisition of practical skills. In the perceived value survey, the
      course methodology was rated at 9.3, organization 9.9, teaching staff 9.6,
      lectures 9 and practical sessions 9.1. CONCLUSIONS: Specifically designed CRRT
      and PD courses are adequate for teaching the theoretical aspects and training
      these procedures. The combination of laboratory, training with animals and
      advanced simulation scenarios might have a synergistic effect on learning.

PMID- 21965591
TI  - Progression of coronary artery calcification in renal transplant recipients.
AB  - BACKGROUND: Cardiovascular disease is the leading cause of mortality among renal
      transplant recipients. In the general population, coronary artery calcification
      (CAC) and progression of CAC are predictors of future cardiac risk. We conducted
      a study to determine the progression of CAC in renal transplant recipients; we
      also examined the factors associated with progression and the impact of the
      analytic methods used to determine CAC progression. METHODS: We used multi
      detector computed tomography to examine CAC in 150 prevalent renal transplant
      recipients, who did not have a documented cardiovascular disease. A baseline and
      a follow-up scan were performed and changes in CAC scores were evaluated in each
      patient individually, to calculate the incidence of CAC progression. Multivariate
      logistic regression analysis was used to evaluate the determinants of CAC
      progression. RESULTS: Baseline CAC prevalence was 35.3% and the mean CAC score
      was 60.0 +/- 174.8. At follow-up scan that was performed after an average of 2.8
      +/- 0.4 years, CAC prevalence increased to 64.6% and the mean CAC score to 94.9
      +/- 245.7. Progression of individual CAC score was found between 28.0 and 38.0%,
      depending on the method used to define progression. In patients with baseline
      CAC, median annualized rate of CAC progression was 11.1. Baseline CAC, high
      triglyceride and bisphosphonate use were the independent determinants of CAC
      progression. CONCLUSIONS: Renal transplantation does not stop or reverse CAC.
      Progression of CAC is the usual evolution pattern of CAC in renal transplant
      recipients. Beside baseline CAC, high triglyceride level and bisphosphonate use
      were associated with progression of CAC.

PMID- 21965592
TI  - Measuring the population burden of chronic kidney disease: a systematic
      literature review of the estimated prevalence of impaired kidney function.
AB  - BACKGROUND: Internationally, there have been substantial efforts to improve the
      early identification of chronic kidney disease (CKD), with a view to improving
      survival, reducing progression and minimizing cardiovascular morbidity and
      mortality. In 2002, a new and globally adopted definition of CKD was introduced.
      The burden of kidney function impairment in the population is unclear and widely
      ranging prevalence estimates have been reported. METHODS: We conducted a
      systematic literature review, searching databases to June 2009. We included all
      adult population screening studies and studies based on laboratory or clinical
      datasets where the denominator was clear. Studies reporting prevalence estimates
      based on at least one eGFR <60 mL/min/1.73m(2) or elevated creatinine above a
      stated threshold were included. Study design and quality were explored as
      potential factors leading to heterogeneity. RESULTS: We identified 43 eligible
      studies (57 published reports) for inclusion. Substantial heterogeneity was
      observed with estimated prevalence (0.6-42.6%). The included studies demonstrated
      significant variation in methodology and quality that impacted on the
      comparability of their findings. From the higher quality studies, the six studies
      measuring impaired kidney function (iKF) using estimated glomerular filtration
      rate in community screening samples reported a prevalence ranging from 1.7% in a
      Chinese study to 8.1% in a US study, with four reporting an estimated prevalence
      of 3.2-5.6%. Heterogeneity was driven by the measure used, study design and study
      population. CONCLUSION: In the general population, estimated iKF, particularly
      eGFR 30-59 mL/min/1.73m(2) was common with prevalence similar to diabetes
      mellitus. Appropriate care of patients poses a substantial global health care
      challenge.

PMID- 21965593
TI  - Exploring the feasibility of alternative STD-testing venues and results delivery
      channels for a national screening campaign.
AB  - Annual chlamydia screening is recommended for sexually active women aged 25 years
      and younger, though less than half of eligible women are screened each year. If
      acceptable to young women, nontraditional testing venues and new communication
      technologies could promote efficiencies in sexually transmitted disease (STD)
      screening and facilitate screening by overcoming barriers at systems and patient
      levels. OBJECTIVE: This study sought to explore young women's technology use,
      preferences for STD-testing venues, attitudes toward nontraditional venues, and
      acceptability of test results delivery options. METHOD: A total of 80
      ethnographic one-on-one telephone interviews were conducted with African
      American, Caucasian, and Latina women, aged 15 to 25 years, in 10 metropolitan
      areas of the United States. Interviews were recorded, transcribed, and analyzed
      using NVivo2. RESULTS: Alternative STD-testing venues and results delivery
      channels are valued by young women for their convenience and accessibility, but
      they must also offer privacy, confidentiality, and emotional/informational
      support to be acceptable. Assuring provider (or self) competence and
      valid/accurate test results is also important. CONCLUSIONS: Although new
      technologies have been embraced by young women for personal and social uses, they
      may not be as readily embraced for the provision of STD-related services.
      Additional social marketing efforts may be needed to promote acceptance of
      nontraditional STD-testing settings and results delivery methods.

PMID- 21965594
TI  - Using mixed methods to measure the perception of community capacity in an
      academic-community partnership for a walking intervention.
AB  - H.U.B. City Steps is a 5-year community-based participatory research walking
      intervention designed to help lower blood pressure in a majority African American
      population in southern Mississippi via community collaboration and capacity
      building, increased walking, culturally tailored health education sessions, and
      motivational interviewing. Building community capacity for physical activity is a
      key component of this intervention. Qualitative and quantitative methods have
      been used to assess how project stakeholders perceive the community capacity
      building efforts of the project. This article illustrates the baseline results of
      this mixed methods approach from the perspective of three groups of stakeholders:
      project researchers and staff, community advisory board, and intervention walking
      coaches. Eight constructs were examined, including leadership, resources,
      external networking, visibility and recognition, personnel sustainability,
      ability and commitment to organize, communication with community members, and
      relationships with influential others. Quantitative results indicated significant
      differences among stakeholder groups for project leadership and personnel
      sustainability. Qualitative perspectives provided an opportunity to examine
      possible reasons for these differences. Overall findings provide direction
      related to improving intervention outcomes and sustainability.

PMID- 21965595
TI  - Combined systemic and local delivery of stem cell inducing/recruiting factors for
      in situ tissue regeneration.
AB  - Whereas the conventional tissue engineering strategy involves the use of
      scaffolds combined with appropriate cell types to restore normal functions, the
      concept of in situ tissue regeneration uses host responses to a target-specific
      scaffold to mobilize host cells to a site of injury without the need for cell
      seeding. For this purpose, local delivery of bioactive molecules from scaffolds
      has been generally used. However, this approach has limited stem cell recruitment
      into the implants. Thus, we developed a combination of systemic delivery of
      substance P (SP) and local release of stromal-derived factor-1alpha (SDF-1alpha)
      from an implant. In this study, we examined whether this combined system would
      significantly enhance recruitment of host stem cells into the implants. Flow
      cytometry and immunohistochemistry for CD29/CD45, CD146/alpha-smooth muscle
      actin, and c-kit demonstrated that this system significantly increased the number
      of stem cell-like cells within the implants when compared with other systems. In
      vitro culture of the cells that had infiltrated into the scaffolds from the
      combined system confirmed that host stem cells were recruited into these implants
      and indicated that they were capable of differentiation into multiple lineages.
      These results indicate that this combined system may lead to more efficient
      tissue regeneration.

PMID- 21965597
TI  - Microparticle-associated nucleic acids mediate trait dominance in cancer.
AB  - Drug resistance is a major cause of cancer treatment failure, with multidrug
      resistance (MDR) being the most serious, whereby cancer cells display cross
      resistance to structurally and functionally unrelated drugs. MDR is caused by
      overexpression of the efflux transporters P-glycoprotein (P-gp) and multidrug
      resistance-associated protein 1 (MRP1). These transporters act to maintain
      sublethal intracellular drug concentrations within the cancer cell, making the
      population treatment unresponsive. Recently, we discovered a novel nongenetic
      basis to MDR whereby microparticles (MPs) transfer P-gp intercellularly from MDR
      donor cells to drug-sensitive recipient cells. MPs isolated from MDR leukemia and
      breast cancer cells were cocultured with their drug-sensitive counterparts. P-gp
      transfer was assessed by direct immunolabeling, and acquired transcripts and
      regulatory microRNAs by quantitative real-time PCR. We show that MDR MPs
      incorporate nucleic acids; MPs change recipient cells' transcriptional
      environment to reflect donor MDR phenotype, and distinct pathways exist among
      cancers of different origin that may be dependent on donor cells' ABCB1
      overexpression. We demonstrate that this pathway exists for both hematological
      and nonhematological malignancies. By conferring MDR and "retemplating" the
      transcriptional landscape of recipient cells, MPs provide a novel pathway, having
      implications in the dissemination and acquisition of deleterious traits in
      clinical oncology.

PMID- 21965596
TI  - Mechanism of anchoring of OmpA protein to the cell wall peptidoglycan of the gram
      negative bacterial outer membrane.
AB  - The outer membrane protein A (OmpA) plays important roles in anchoring of the
      outer membrane to the bacterial cell wall. The C-terminal periplasmic domain of
      OmpA (OmpA-like domain) associates with the peptidoglycan (PGN) layer
      noncovalently. However, there is a paucity of information on the structural
      aspects of the mechanism of PGN recognition by OmpA-like domains. To elucidate
      this molecular recognition process, we solved the high-resolution crystal
      structure of an OmpA-like domain from Acinetobacter baumannii bound to
      diaminopimelate (DAP), a unique bacterial amino acid from the PGN. The structure
      clearly illustrates that two absolutely conserved Asp271 and Arg286 residues are
      the key to the binding to DAP of PGN. Identification of DAP as the central
      anchoring site of PGN to OmpA is further supported by isothermal titration
      calorimetry and a pulldown assay with PGN. An NMR-based computational model for
      complexation between the PGN and OmpA emerged, and this model is validated by
      determining the crystal structure in complex with a synthetic PGN fragment. These
      structural data provide a detailed glimpse of how the anchoring of OmpA to the
      cell wall of gram-negative bacteria takes place in a DAP-dependent manner.

PMID- 21965598
TI  - Effective detection of fetal sex using circulating fetal DNA in first-trimester
      maternal plasma.
AB  - The aim of this study was to develop a simple and effective method for
      noninvasively detecting fetal sex using circulating fetal DNA from first
      trimester maternal plasma. A study was conducted with maternal plasma collected
      from 203 women between 5 and 12 wk of gestation. The presence of circulating
      fetal DNA was confirmed by a quantitative methylation-specific polymerase chain
      reaction of the unmethylated-PDE9A gene (U-PDE9A). Multiplex real-time PCR was
      used to simultaneously quantify the amount of DYS14 and GAPDH in maternal plasma.
      The results were confirmed by phenotype at birth. Pregnancy outcomes and U-PDE9A
      concentrations were obtained in all cases, including 99 male-bearing and 104
      female-bearing participants. At equivalent specificity (100%), the false-negative
      rate was 9.1% for DYS14 quantification cycle, 7.1% for DYS14 concentration, and
      0.0% for the concentration ratio of DYS14/GAPDH, respectively. In male-bearing
      participants, DYS14, U-PDE9A, and GAPDH concentrations were significantly lower
      in the false-negative case than in correct case (P<0.001 in all). Moreover,
      DYS14, U-PDE9A, and GAPDH concentrations showed significantly positive
      associations with each other (P<=0.001 in all). The ratio of DYS14/GAPDH in
      maternal plasma was an effective biomarker for noninvasive fetal sex detection
      during the first trimester, indicating that it could be useful for clinical
      application.

PMID- 21965599
TI  - Amylin is a novel neuropeptide with potential maternal functions in the rat.
AB  - Amylin, a 37-aa pancreatic peptide, was found to be expressed in the preoptic
      area of mother rats in our recent microarray study. Here, we report a marked
      increase in amylin expression around parturition and show that amylin mRNA level
      remains elevated as long as the pups are not removed from the dams. Amylin
      expression is also induced in maternally behaving (sensitized) nonlactating but
      not in nonsensitized nulliparous females or in females that did not become
      maternal despite the sensitization procedure. Immunohistochemistry verified the
      increased amylin peptide expression in maternally behaving rats and demonstrated
      the same expression pattern of amylin as in situ hybridization histochemistry.
      Ovariectomy had no effect on the activation of amylin neurons, suggesting sexual
      steroid-independent mechanisms. In subsequent functional experiments, mothers
      were separated from their pups for 22 h. On return of the pups, neuronal
      activation was found in the mother's preoptic area, with a distribution pattern
      similar to amylin-expressing neurons. Subsequent double labeling revealed that 86
      93% of amylin neurons were activated by pup exposure. The results implicate
      amylin in the control of maternal adaptations, possibly exerting its actions on
      maternal behaviors via amylin receptors present in brain regions to which
      preoptic neurons project.

PMID- 21965600
TI  - Clathrin is required for postmitotic Golgi reassembly.
AB  - During the G2-M transition, the highly organized Golgi apparatus undergoes
      reversible fragmentation through unstacking of the cisternal ribbon and
      disassembly into radially dispersed vesicles and tubules. These Golgi-derived
      fragments redistribute randomly within the cytoplasm, partition stochastically,
      and in telophase coalesce to generate a functionally and structurally intact
      Golgi complex. Here we identified a novel step in postmitotic Golgi reassembly
      that requires the clathrin heavy chain (CHC). We used siRNA-mediated CHC
      knockdown, biochemistry, and morphological analysis and showed that the spindle-
      and spindle pole-associated clathrin pools are membrane-bound and required for
      postmitotic Golgi reassembly. The results presented here show that clathrin
      remains associated with the spindle poles throughout mitosis and that this
      clathrin pool is distinct from the previously characterized spindle-associated
      population. We suggest that clathrin may provide a template for postmitotic Golgi
      reassembly and cisternal remodeling. In absence of the CHC, the Golgi apparatus
      remained disconnected and disordered and failed to regain its characteristic
      perinuclear, lace-like morphology. Our findings build on previous independent
      reports that clathrin is required for Golgi reassembly following disruption with
      pharmacological agents and for mitotic chromosome congression.

PMID- 21965601
TI  - Disease-related amyloidogenic variants of human lysozyme trigger the unfolded
      protein response and disturb eye development in Drosophila melanogaster.
AB  - We have created a Drosophila model of lysozyme amyloidosis to investigate the in
      vivo behavior of disease-associated variants. To achieve this objective, wild
      type (WT) protein and the amyloidogenic variants F57I and D67H were expressed in
      Drosophila melanogaster using the UAS-gal4 system and both the ubiquitous and
      retinal expression drivers Act5C-gal4 and gmr-gal4. The nontransgenic w(1118)
      Drosophila line was used as a control throughout. We utilized ELISA experiments
      to probe lysozyme protein levels, scanning electron microscopy for eye phenotype
      classification, and immunohistochemistry to detect the unfolded protein response
      (UPR) activation. We observed that expressing the destabilized F57I and D67H
      lysozymes triggers UPR activation, resulting in degradation of these variants,
      whereas the WT lysozyme is secreted into the fly hemolymph. Indeed, the level of
      WT was up to 17 times more abundant than the variant proteins. In addition, the
      F57I variant gave rise to a significant disruption of the eye development, and
      this correlated to pronounced UPR activation. These results support the concept
      that the onset of familial amyloid disease is linked to an inability of the UPR
      to degrade completely the amyloidogenic lysozymes prior to secretion, resulting
      in secretion of these destabilized variants, thereby leading to deposition and
      associated organ damage.

PMID- 21965602
TI  - Mature N-linked glycans facilitate UT-A1 urea transporter lipid raft
      compartmentalization.
AB  - The UT-A1 urea transporter is a glycoprotein with two different glycosylated
      forms of 97 and 117 kDa. In this study, we found the 117-kDa UT-A1 preferentially
      resides in lipid rafts, suggesting that the glycosylation status may interfere
      with UT-A1 lipid raft trafficking. This was confirmed by a site-directed
      mutagenesis study in MDCK cells. The nonglycosylated UT-A1 showed reduced
      localization in lipid rafts. By using sugar-specific binding lectins, we further
      found that the UT-A1 in nonlipid rafts contained a high amount of mannose, as
      detected by concanavalin A, while the UT-A1 in lipid rafts was the mature N
      acetylglucosamine-containing form, as detected by wheat germ agglutinin. In the
      inner medulla (IM) of diabetic rats, the more abundant 117-kDa UT-A1 in lipid
      rafts was the mature glycosylation form, with high amounts of N-acetylglucosamine
      and sialic acid. In contrast, in the IM of normal rats, the predominant 97-kDa UT
      A1 was the form enriched in mannose. Functionally, inhibition of glycosylation by
      tunicamycin or elimination of the glycosylation sites by mutation significantly
      reduced UT-A1 activity in oocytes. Taken together, our study reveals a new role
      of N-linked glycosylation in regulating UT-A1 activity by promoting UT-A1
      trafficking into membrane lipid raft subdomains.

PMID- 21965603
TI  - Origin-specific epigenetic program correlates with vascular bed-specific
      differences in Rgs5 expression.
AB  - Cells from multiple origins contribute to vascular smooth muscle cell (VSMC)
      development. Phenotypic heterogeneity of VSMCs is associated with their point of
      developmental origin; however, the mechanisms driving such differences are
      unknown. We here examined the mechanisms controlling vascular bed-specific
      differences in Rgs5 expression during development. Rgs5 levels were similar
      across different regions of the vasculature in neonatal animals but were >15-fold
      higher in descending aortas compared with carotid arteries of adult mice. Thus,
      vessel bed-specific changes in regulation of Rgs5 expression occurred during
      vessel maturation. Examination of adult Rgs5-LacZ reporter mice revealed lower
      Rgs5 expression in VSMCs originating from the third (carotid artery) branchial
      arch compared with those originating in the fourth and sixth (aortic B segment,
      right subclavian, and ductus arteriosus) branchial arches. Indeed, a mosaic Rgs5
      expression pattern, with discreet LacZ boundaries between VSMCs derived from
      different developmental origins, was observed. Furthermore, Rgs5-LacZ expression
      was correlated with the site of VSMC origin (splanchic mesoderm ~ local
      mesenchyme > somites > proepicardium > mesothelium). Surprisingly, Rgs5 reporter
      activity in cultured carotid artery- and descending aorta-derived cells did not
      recapitulate the differences observed in vivo. Consistent with a developmental
      origin-specific epigenetic mechanism driving the observed expression differences
      in vivo, the Rgs5 promoter showed increased methylation on CpG dinucleotides in
      carotid arteries compared with that in descending aortas in adult but not in
      neonatal mice. In vitro methylation of the Rgs5 promoter confirmed that its
      activity is sensitive to transcriptional down-regulation by CpG methylation.
      These data suggest that an origin-dependent epigenetic program regulates vascular
      bed- and maturation state-dependent regulation of VSMC-specific gene
      transcription.

PMID- 21965604
TI  - Tandem reporter assay for myristoylated proteins post-translationally (TRAMPP)
      identifies novel substrates for post-translational myristoylation: PKCepsilon, a
      case study.
AB  - Myristoylation, the addition of a 14-carbon fatty acid to the N-terminal glycine
      of a protein, is key to protein-membrane and protein-protein interactions.
      Typically, myristoylation occurs cotranslationally; however, post-translational
      myristoylation of caspase-cleaved proteins is now emerging as a well-established
      protein modification and as a novel regulator of apoptosis. To identify
      additional post-translationally myristoylated proteins, we engineered a plasmid
      vector encoding for a caspase-cleavable reporter protein named tandem reporter
      assay for myristoylation of proteins post-translationally (TRAMPP). pTRAMPP
      consists of tdTomato-DEVD-"test myristoylation sequence"-enhanced green
      fluorescent protein (EGFP). After induction of apoptosis, the reporter protein is
      cleaved by caspases, which frees a new N-terminal glycine residue attached to
      EGFP that can be myristoylated. We used pTRAMPP in appropriately transfected
      cells to identify 7 post-translationally myristoylated proteins. First, we
      confirmed the post-translational myristoylation of two previously identified
      putative substrates, cytoplasmic dynein intermediate chain 2A and PKCepsilon
      (ctPKCepsilon), and identified 5 more caspase-cleaved potential substrates for
      myristoylation that include the antiapoptotic regulator of apoptosis, Mcl-1, and
      the causative agent of Huntington's disease, huntingtin protein. Further
      investigation revealed that post-translationally myristoylated ctPKCepsilon
      localized to membranes and increased Erk signaling and degradation of the
      proapoptotic protein Bim, which prevented a significant loss of mitochondrial
      potential of 17% over nonmyristoylated ctPKCepsilon in HeLa cells in the presence
      of apoptotic stimuli. Taken together, these findings suggest a possible
      antiapoptotic role for post-translationally myristoylated caspase-cleaved
      ctPKCepsilon.

PMID- 21965605
TI  - Mouse ghrelin-O-acyltransferase (GOAT) plays a critical role in bile acid
      reabsorption.
AB  - Ghrelin is a unique peptide gut hormone that requires post-translational
      modification to stimulate both feeding and growth hormone release. Ghrelin O
      acyltransferase (GOAT) was identified as a specific acyl-transferase for ghrelin,
      and recent genetic deletion studies of the Goat gene (Goat(-/-)) uncovered the
      role of ghrelin in the regulation of glucose homeostasis. To further understand
      the physiological functions of the GOAT/ghrelin system, we have conducted a
      metabolomic and microarray profile of Goat-null mice, as well as determined Goat
      expression in different tissues using the lacZ reporter gene. Serum metabolite
      profile analysis revealed that Goat(-/-) mice exhibited increased secondary bile
      acids >2.5-fold. This was attributed to increased mRNA and protein expression of
      the ileal sodium-dependent bile acid transporter (ISBT) in the intestinal and
      biliary tract. Increased expression of additional solute carrier proteins,
      including Slc5a12 (>10-fold) were also detected in the small intestine and bile
      duct. Goat staining was consistently observed in the pituitary glands, stomach,
      and intestines, and to a lesser extent in the gallbladder and pancreatic duct.
      This is the first report that the GOAT/ghrelin system regulates bile acid
      metabolism, and these findings suggest a novel function of GOAT in the regulation
      of intestinal bile acid reabsorption..

PMID- 21965606
TI  - Tomato TILLING technology: development of a reverse genetics tool for the
      efficient isolation of mutants from Micro-Tom mutant libraries.
AB  - To accelerate functional genomic research in tomato, we developed a Micro-Tom
      TILLING (Targeting Induced Local Lesions In Genomes) platform. DNA pools were
      constructed from 3,052 ethyl methanesulfonate (EMS) mutant lines treated with 0.5
      or 1.0% EMS. The mutation frequency was calculated by screening 10 genes. The
      0.5% EMS population had a mild mutation frequency of one mutation per 1,710 kb,
      whereas the 1.0% EMS population had a frequency of one mutation per 737 kb, a
      frequency suitable for producing an allelic series of mutations in the target
      genes. The overall mutation frequency was one mutation per 1,237 kb, which
      affected an average of three alleles per kilobase screened. To assess whether a
      Micro-Tom TILLING platform could be used for efficient mutant isolation, six
      ethylene receptor genes in tomato (SlETR1-SlETR6) were screened. Two allelic
      mutants of SlETR1 (Sletr1-1 and Sletr1-2) that resulted in reduced ethylene
      responses were identified, indicating that our Micro-Tom TILLING platform
      provides a powerful tool for the rapid detection of mutations in an EMS mutant
      library. This work provides a practical and publicly accessible tool for the
      study of fruit biology and for obtaining novel genetic material that can be used
      to improve important agronomic traits in tomato.

PMID- 21965607
TI  - Detection and quantification of S-nitrosoglutathione (GSNO) in pepper (Capsicum
      annuum L.) plant organs by LC-ES/MS.
AB  - Glutathione (GSH) is one of the major, soluble, low molecular weight
      antioxidants, as well as the major non-protein thiol in plant cells. However, the
      relevance of this molecule could be even greater considering that it can react
      with nitric oxide (NO) to generate S-nitrosoglutathione (GSNO) which is
      considered to function as a mobile reservoir of NO bioactivity in plants.
      Although this NO-derived molecule has an increased physiological and
      phytopathological relevance in plants cells, its identification and
      quantification in plant tissues have not be reported so far. Using liquid
      chromatography-electrospray/mass spectrometry (LC-ES/MS), a method was set up to
      detect and quantify simultaneously GSNO as well reduced and oxidized glutathione
      (GSH and GSSG, respectively) in different pepper plant organs including roots,
      stems and leaves, and in Arabidopsis leaves. The analysis of NO and GSNO
      reductase (GSNOR) activity in these pepper organs showed that the content of GSNO
      was directly related to the content of NO in each organ and oppositely related to
      the GSNOR activity. This approach opens up new analytical possibilities to
      understand the relevance of GSNO in plant cells under physiological and stress
      conditions.

PMID- 21965608
TI  - The transcription factor BELLRINGER modulates phyllotaxis by regulating the
      expression of a pectin methylesterase in Arabidopsis.
AB  - Plant leaves and flowers are positioned along the stem in a regular pattern. This
      pattern, which is referred to as phyllotaxis, is generated through the precise
      emergence of lateral organs and is controlled by gradients of the plant hormone
      auxin. This pattern is actively maintained during stem growth through controlled
      cell proliferation and elongation. The formation of new organs is known to depend
      on changes in cell wall chemistry, in particular the demethylesterification of
      homogalacturonans, one of the main pectic components. Here we report a dual
      function for the homeodomain transcription factor BELLRINGER (BLR) in the
      establishment and maintenance of the phyllotactic pattern in Arabidopsis. BLR is
      required for the establishment of normal phyllotaxis through the exclusion of
      pectin methylesterase PME5 expression from the meristem dome and for the
      maintenance of phyllotaxis through the activation of PME5 in the elongating stem.
      These results provide new insights into the role of pectin demethylesterification
      in organ initiation and cell elongation and identify an important component of
      the regulation mechanism involved.

PMID- 21965609
TI  - Partially redundant proneural function reveals the importance of timing during
      zebrafish olfactory neurogenesis.
AB  - Little is known about proneural gene function during olfactory neurogenesis in
      zebrafish. Here, we show that the zebrafish Atonal genes neurogenin1 (neurog1)
      and neurod4 are redundantly required for development of both early-born olfactory
      neurons (EONs) and later-born olfactory sensory neurons (OSNs). We show that
      neurod4 expression is initially absent in neurog1 mutant embryos but recovers and
      is sufficient for the delayed development of OSN. By contrast, EON numbers are
      significantly reduced in neurog1 mutant embryos despite the recovery of neurod4
      expression. Our results suggest that a shortened time window for EON development
      causes this reduction; the last S-phase of EON is delayed in neurog1 mutant
      embryos but mutant EONs are all post-mitotic at the same stage as EONs in wild
      type embryos. Finally, we show that expression of certain genes, such as robo2,
      is never detected in neurog1 mutant EONs. Failure of robo2 expression to recover
      correlates with defects in the fasciculation of neurog1 mutant olfactory axonal
      projections and in the organisation of proto-glomeruli because projections arrive
      at the olfactory bulb that are reminiscent of those in robo2 mutant embryos. We
      conclude that the duration of proneural expression in EON progenitors is crucial
      for correct development of the zebrafish olfactory system.

PMID- 21965610
TI  - Coordinating cell behaviour during blood vessel formation.
AB  - The correct development of blood vessels is crucial for all aspects of tissue
      growth and physiology in vertebrates. The formation of an elaborate
      hierarchically branched network of endothelial tubes, through either angiogenesis
      or vasculogenesis, relies on a series of coordinated morphogenic events, but how
      individual endothelial cells adopt specific phenotypes and how they coordinate
      their behaviour during vascular patterning is unclear. Recent progress in our
      understanding of blood vessel formation has been driven by advanced imaging
      techniques and detailed analyses that have used a combination of powerful in
      vitro, in vivo and in silico model systems. Here, we summarise these models and
      discuss their advantages and disadvantages. We then review the different stages
      of blood vessel development, highlighting the cellular mechanisms and molecular
      players involved at each step and focusing on cell specification and coordination
      within the network.

PMID- 21965612
TI  - Angiogenic morphogenesis driven by dynamic and heterogeneous collective
      endothelial cell movement.
AB  - Angiogenesis is a complex process, which is accomplished by reiteration of
      modules such as sprouting, elongation and bifurcation, that configures branching
      vascular networks. However, details of the individual and collective behaviors of
      vascular endothelial cells (ECs) during angiogenic morphogenesis remain largely
      unknown. Herein, we established a time-lapse imaging and computer-assisted
      analysis system that quantitatively characterizes behaviors in sprouting
      angiogenesis. Surprisingly, ECs moved backwards and forwards, overtaking each
      other even at the tip, showing an unknown mode of collective cell movement with
      dynamic 'cell-mixing'. Mosaic analysis, which enabled us to monitor the behavior
      of individual cells in a multicellular structure, confirmed the 'cell-mixing'
      phenomenon of ECs that occurs at the whole-cell level. Furthermore, an in vivo EC
      tracking analysis revealed evidence of cell-mixing and overtaking at the tip in
      developing murine retinal vessels. In parametrical analysis, VEGF enhanced tip
      cell behavior and directed EC migration at the stalk during branch elongation.
      These movements were counter-regulated by EC-EC interplay via gamma-secretase
      dependent Dll4-Notch signaling, and might be promoted by EC-mural cell interplay.
      Finally, multiple regression analysis showed that these molecule-mediated tip
      cell behaviors and directed EC migration contributed to effective branch
      elongation. Taken together, our findings provide new insights into the individual
      and collective EC movements driving angiogenic morphogenesis. The methodology
      used for this analysis might serve to bridge the gap in our understanding between
      individual cell behavior and branching morphogenesis.

PMID- 21965611
TI  - Neuronal Neuregulin 1 type III directs Schwann cell migration.
AB  - During peripheral nerve development, each segment of a myelinated axon is matched
      with a single Schwann cell. Tight regulation of Schwann cell movement,
      proliferation and differentiation is essential to ensure that these glial cells
      properly associate with axons. ErbB receptors are required for Schwann cell
      migration, but the operative ligand and its mechanism of action have remained
      unknown. We demonstrate that zebrafish Neuregulin 1 (Nrg1) type III, which
      signals through ErbB receptors, controls Schwann cell migration in addition to
      its previously known roles in proliferation and myelination. Chimera analyses
      indicate that ErbB receptors are required in all migrating Schwann cells, and
      that Nrg1 type III is required in neurons for migration. Surprisingly, expression
      of the ligand in a few axons is sufficient to induce migration along a chimeric
      nerve constituted largely of nrg1 type III mutant axons. These studies also
      reveal a mechanism that allows Schwann cells to fasciculate axons regardless of
      nrg1 type III expression. Time-lapse imaging of transgenic embryos demonstrated
      that misexpression of human NRG1 type III results in ectopic Schwann cell
      migration, allowing them to aberrantly enter the central nervous system. These
      results demonstrate that Nrg1 type III is an essential signal that controls
      Schwann cell migration to ensure that these glia are present in the correct
      numbers and positions in developing nerves.

PMID- 21965613
TI  - COUP-TFI promotes radial migration and proper morphology of callosal projection
      neurons by repressing Rnd2 expression.
AB  - During corticogenesis, late-born callosal projection neurons (CPNs) acquire their
      laminar position through glia-guided radial migration and then undergo final
      differentiation. However, the mechanisms controlling radial migration and final
      morphology of CPNs are poorly defined. Here, we show that in COUP-TFI mutant mice
      CPNs are correctly specified, but are delayed in reaching the cortical plate and
      have morphological defects during migration. Interestingly, we observed that the
      rate of neuronal migration to the cortical plate normally follows a low-rostral
      to high-caudal gradient, similar to that described for COUP-TFI. This gradient is
      strongly impaired in COUP-TFI(-/-) brains. Moreover, the expression of the Rho
      GTPase Rnd2, a modulator of radial migration, is complementary to both these
      gradients and strongly increases in the absence of COUP-TFI function. We show
      that COUP-TFI directly represses Rnd2 expression at the post-mitotic level along
      the rostrocaudal axis of the neocortex. Restoring correct Rnd2 levels in COUP
      TFI(-/-) brains cell-autonomously rescues neuron radial migration and
      morphological transitions. We also observed impairments in axonal elongation and
      dendritic arborization of COUP-TFI-deficient CPNs, which were rescued by lowering
      Rnd2 expression levels. Thus, our data demonstrate that COUP-TFI modulates late
      born neuron migration and favours proper differentiation of CPNs by finely
      regulating Rnd2 expression levels.

PMID- 21965614
TI  - Defective neuroepithelial cell cohesion affects tangential branchiomotor neuron
      migration in the zebrafish neural tube.
AB  - Facial branchiomotor neurons (FBMNs) in zebrafish and mouse embryonic hindbrain
      undergo a characteristic tangential migration from rhombomere (r) 4, where they
      are born, to r6/7. Cohesion among neuroepithelial cells (NCs) has been suggested
      to function in FBMN migration by inhibiting FBMNs positioned in the basal
      neuroepithelium such that they move apically between NCs towards the midline of
      the neuroepithelium instead of tangentially along the basal side of the
      neuroepithelium towards r6/7. However, direct experimental evaluation of this
      hypothesis is still lacking. Here, we have used a combination of biophysical cell
      adhesion measurements and high-resolution time-lapse microscopy to determine the
      role of NC cohesion in FBMN migration. We show that reducing NC cohesion by
      interfering with Cadherin 2 (Cdh2) activity results in FBMNs positioned at the
      basal side of the neuroepithelium moving apically towards the neural tube midline
      instead of tangentially towards r6/7. In embryos with strongly reduced NC
      cohesion, ectopic apical FBMN movement frequently results in fusion of the
      bilateral FBMN clusters over the apical midline of the neural tube. By contrast,
      reducing cohesion among FBMNs by interfering with Contactin 2 (Cntn2) expression
      in these cells has little effect on apical FBMN movement, but reduces the fusion
      of the bilateral FBMN clusters in embryos with strongly diminished NC cohesion.
      These data provide direct experimental evidence that NC cohesion functions in
      tangential FBMN migration by restricting their apical movement.

PMID- 21965615
TI  - Blood vessels restrain pancreas branching, differentiation and growth.
AB  - How organ size and form are controlled during development is a major question in
      biology. Blood vessels have been shown to be essential for early development of
      the liver and pancreas, and are fundamental to normal and pathological tissue
      growth. Here, we report that, surprisingly, non-nutritional signals from blood
      vessels act to restrain pancreas growth. Elimination of endothelial cells
      increases the size of embryonic pancreatic buds. Conversely, VEGF-induced
      hypervascularization decreases pancreas size. The growth phenotype results from
      vascular restriction of pancreatic tip cell formation, lateral branching and
      differentiation of the pancreatic epithelium into endocrine and acinar cells. The
      effects are seen both in vivo and ex vivo, indicating a perfusion-independent
      mechanism. Thus, the vasculature controls pancreas morphogenesis and growth by
      reducing branching and differentiation of primitive epithelial cells.

PMID- 21965616
TI  - Distinct levels of Notch activity for commitment and terminal differentiation of
      stem cells in the adult fly intestine.
AB  - Tight regulation of self-renewal and differentiation of adult stem cells ensures
      that tissues are properly maintained. In the Drosophila intestine, both
      commitment, i.e. exit from self-renewal, and terminal differentiation are
      controlled by Notch signaling. Here, we show that distinct requirements for Notch
      activity exist: commitment requires high Notch activity, whereas terminal
      differentiation can occur with lower Notch activity. We identified the gene GDP
      mannose 4,6-dehydratase (Gmd), a modulator of Notch signaling, as being required
      for commitment but dispensable for terminal differentiation. Gmd loss resulted in
      aberrant, self-renewing stem cell divisions that generated extra ISC-like cells
      defective in Notch reporter activation, as well as wild-type-like cell divisions
      that produced properly terminally differentiated cells. Lowering Notch signaling
      using additional genetic means, we provided further evidence that commitment has
      a higher Notch signaling requirement than terminal differentiation. Our work
      suggests that a commitment requirement for high-level Notch activity safeguards
      the stem cells from loss through differentiation, revealing a novel role for the
      importance of Notch signaling levels in this system.

PMID- 21965617
TI  - JAK/Stat signaling regulates heart precursor diversification in Drosophila.
AB  - Intercellular signal transduction pathways regulate the NK-2 family of
      transcription factors in a conserved gene regulatory network that directs
      cardiogenesis in both flies and mammals. The Drosophila NK-2 protein Tinman (Tin)
      was recently shown to regulate Stat92E, the Janus kinase (JAK) and Signal
      transducer and activator of transcription (Stat) pathway effector, in the
      developing mesoderm. To understand whether the JAK/Stat pathway also regulates
      cardiogenesis, we performed a systematic characterization of JAK/Stat signaling
      during mesoderm development. Drosophila embryos with mutations in the JAK/Stat
      ligand upd or in Stat92E have non-functional hearts with luminal defects and
      inappropriate cell aggregations. Using strong Stat92E loss-of-function alleles,
      we show that the JAK/Stat pathway regulates tin expression prior to heart
      precursor cell diversification. tin expression can be subdivided into four phases
      and, in Stat92E mutant embryos, the broad phase 2 expression pattern in the
      dorsal mesoderm does not restrict to the constrained phase 3 pattern. These
      embryos also have an expanded pericardial cell domain. We show the E(spl)-C gene
      HLHm5 is expressed in a pattern complementary to tin during phase 3 and that this
      expression is JAK/Stat dependent. In addition, E(spl)-C mutant embryos phenocopy
      the cardiac defects of Stat92E embryos. Mechanistically, JAK/Stat signals
      activate E(spl)-C genes to restrict Tin expression and the subsequent expression
      of the T-box transcription factor H15 to direct heart precursor diversification.
      This study is the first to characterize a role for the JAK/Stat pathway during
      cardiogenesis and identifies an autoregulatory circuit in which tin limits its
      own expression domain.

PMID- 21965618
TI  - Comparing cardiac surgery in peritoneal dialysis and hemodialysis patients:
      perioperative outcomes and two-year survival.
AB  - BACKGROUND: We sought to compare perioperative outcomes and 2-year survival in a
      cohort of peritoneal dialysis (PD) patients compared with matched hemodialysis
      (HD) patients who underwent cardiothoracic surgery at our institution. METHODS:
      We obtained a list of all dialysis-dependent patients who underwent cardiac
      surgery (coronary artery bypass grafting, valve replacement, or both) at our
      center between 1994 and 2008. All patients undergoing PD at the time of surgery
      were included in our analysis. Two HD patients matched for age, diabetes status,
      and Charleston comorbidity score were obtained for each PD patient. RESULTS: The
      analysis included 36 PD patients and 72 HD patients. Mean age, sex, diabetes
      status, cardiac unit stay, hospital stay, and operative mortality did not differ
      by dialysis modality. The incidence of 1 or more postoperative complications
      (infection, prolonged intubation, death) was higher for HD patients (50% vs. 28%
      for PD patients, p = 0.046). After surgery, 2 PD patients required conversion to
      HD. The 2-year survival was 69% for PD patients and 66% for HD patients (p =
      0.73). CONCLUSIONS: Our findings suggest that, compared with HD patients, PD
      patients who require cardiac surgery do not experience more early complications
      or a lesser 2-year survival and that 2-year survival for dialysis patients after
      cardiac surgery is acceptable.

PMID- 21965619
TI  - Neuropeptide release augments serum albumin loss and reduces ultrafiltration in
      peritoneal dialysis.
AB  - BACKGROUND: The triggers of the acute local inflammatory response to peritoneal
      dialysis (PD) fluid exposure remain unknown. In the present study, we
      investigated the effects of neurogenic inflammation and mast cell degranulation
      on water and solute transport in experimental PD. METHODS: Single 2-hour dwells
      in rats with PD catheters were studied. Histamine and the neuropeptides substance
      P and calcitonin gene-related peptide (CGRP) were measured in PD fluid samples by
      ELISA. Radiolabeled albumin ((125)I and (131)I respectively) was used as an
      intraperitoneal (IP) and intravascular tracer. Glucose and urea concentrations
      were measured in plasma and PD fluid. The effects of varying the volume and
      osmolarity of a lactate-buffered PD fluid were compared and related to the
      effects of pharmacologic intervention. RESULTS: Application of 20 mL 3.9% glucose
      PD fluid induced an IP histamine release during the first 30 minutes, blockable
      by the mast cell stabilizer doxantrazole and the substance P neurokinin-1
      receptor (NK1R)-blocker spantide. Histamine release was also inhibited at a
      reduced PD volume (14 mL), but was not affected by normalizing the PD fluid
      osmolarity. Blockade of NK1R also reduced plasma albumin leakage to the
      peritoneal cavity. Inhibition of CGRP receptors by CGRP8-37 improved osmotic
      (transcapillary) and net ultrafiltration and reduced the dialysate urea
      concentration. Neuropeptide release was not clearly related to activation of the
      TrpV1 receptor, the classic trigger of neurogenic inflammation. CONCLUSIONS:
      Neuropeptide release exaggerated albumin loss and reduced ultrafiltration in this
      rat PD model. Intervention aimed at the neuropeptide action substantially
      improved PD efficiency.

PMID- 21965620
TI  - Cost-effectiveness analysis of the Spanish renal replacement therapy program.
AB  - BACKGROUND: We undertook a cost-effectiveness analysis of the Spanish Renal
      Replacement Therapy (RRT) program for end-stage renal disease patients from a
      societal perspective. The current Spanish situation was compared with several
      hypothetical scenarios. METHODS: A Markov chain model was used as a foundation
      for simulations of the Spanish RRT program in three temporal horizons (5, 10, and
      15 years). The current situation (scenario 1) was compared with three different
      scenarios: increased proportion of overall scheduled (planned) incident patients
      (scenario 2); constant proportion of overall scheduled incident patients, but
      increased proportion of scheduled incident patients on peritoneal dialysis (PD),
      resulting in a lower proportion of scheduled incident patients on hemodialysis
      (HD) (scenario 3); and increased overall proportion of scheduled incident
      patients together with increased scheduled incidence of patients on PD (scenario
      4). RESULTS: The incremental cost-effectiveness ratios (ICERs) of scenarios 2, 3,
      and 4, when compared with scenario 1, were estimated to be, respectively, -?83
      150, -?354 977, and -?235 886 per incremental quality-adjusted life year
      (DeltaQALY), evidencing both moderate cost savings and slight effectiveness
      gains. The net health benefits that would accrue to society were estimated to be,
      respectively, 0.0045, 0.0211, and 0.0219 DeltaQALYs considering a willingness-to
      pay threshold of ?35 000/DeltaQALY. CONCLUSIONS: Scenario 1, the current Spanish
      situation, was dominated by all the proposed scenarios. Interestingly, scenarios
      3 and 4 showed the best results in terms of cost-effectiveness. From a cost
      effectiveness perspective, an increase in the overall scheduled incidence of RRT,
      and particularly that of PD, should be promoted.

PMID- 21965621
TI  - Effectiveness of home visits to pediatric peritoneal dialysis patients.
AB  - Home visits by trained personnel to patients undergoing home dialysis are
      required, but little is reported about the effectiveness of such home visits. We
      retrospectively reviewed home visits to 22 pediatric patients undergoing
      continuous cycling peritoneal dialysis (PD) at home. A trained dialysis nurse
      completed each home visit. An average of 1.5 pertinent dialysis findings and 1
      pertinent medication finding was noted for each home visit to these patients. The
      interdisciplinary dialysis team reviewed the home visit findings and made
      specific recommendations after each home visit. In addition, the training process
      has been enhanced to incorporate visit findings for future home PD patients.
      Although not statistically significant in this small number of patients,
      peritonitis rates declined in the 6 months after initiation of the home visit
      program. The average cost for a dialysis nurse to complete a home visit is less
      than the cost of antibiotics for 1 episode of peritonitis. Home visits are
      valuable for improving clinical care in pediatric patients on home PD.

PMID- 21965622
TI  - Bupropion hydroxylation as a selective marker of rat CYP2B1 catalytic activity.
AB  - Benzyloxyresorufin-O-dealkylation (BROD) is usually used as a marker of
      cytochrome P450 (P450) 2B1 in rat. However, some reports show that CYP1A2 is also
      highly implicated. The purpose of the present study was to establish bupropion
      (BUP) hydroxylation, but not BROD, as a selective in vitro marker of CYP2B1
      catalytic activity. IC(50) for BROD and BUP hydroxylation were equivalent (40.8
      +/- 4.6 and 41.8 +/- 3.4 MUM, respectively) when using liver microsomes from beta
      naphthoflavone-pretreated rats in the presence of metyrapone (CYP2B1 inhibitor).
      When using the same microsomes in the presence of CYP1A1/2-selective inhibitor
      alpha-naphthoflavone, we found an IC(50) of 2.5 * 10(-3) +/- 0.8 * 10(-3) MUM for
      BROD and >100 MUM for BUP hydroxylation. These results suggest that CYP2B1 is
      similarly involved in both activities, whereas CYP1A2 is involved in BROD
      activity but not in BUP hydroxylation. BUP hydroxylation was assessed in
      microsomes from baculovirus-infected insect cells coexpressing NADPH-P450
      oxidoreductase, and 14 rat P450s and kinetic parameters (K(m) and V(max)) were
      determined. BUP hydroxylation was predominantly catalyzed by CYP2B1 (75% of total
      hydroxybupropion formation), low activity was detected with CYP2E1 and CYP2C11
      (10.9 and 8.7% of total hydroxybupropion, respectively), and activity was almost
      undetectable with the other P450 isoforms at saturating substrate concentrations
      (2500 MUM), thereby validating the use of BUP as a diagnostic in vitro marker of
      CYP2B1 catalytic activity in rat.

PMID- 21965623
TI  - In vitro inhibition of the bile salt export pump correlates with risk of
      cholestatic drug-induced liver injury in humans.
AB  - Inhibition of the activity of the human bile salt export pump (BSEP: ABCB11) has
      been proposed to play a role in drug-induced liver injury (DILI). To enhance
      understanding of the relationship between BSEP inhibition and DILI, inhibition of
      human BSEP (hBSEP) and its rat ortholog (rBsep) by 85 pharmaceuticals was
      investigated in vitro. This was explored using assays that quantified inhibition
      of ATP-dependent [(3)H]taurocholate uptake into inverted plasma membrane vesicles
      from Sf21 insect cells, which expressed the proteins. Of the pharmaceuticals, 40
      exhibited evidence of in vitro transporter inhibition and overall a close
      correlation was observed between potency values for inhibition of hBSEP and rBsep
      activity (r(2) = 0.94), although 12 drugs exhibited >2-fold more potent
      inhibition of hBSEP than rBsep. The median potency of hBSEP inhibition was higher
      among drugs that caused cholestatic/mixed DILI than among drugs that caused
      hepatocellular or no DILI, as was the incidence of hBSEP inhibition with IC(50)
      <300 MUM. All drugs with hBSEP IC(50) <300 MUM had molecular weight >250, ClogP
      >1.5, and nonpolar surface area >180A. A clear distinction was not evident
      between hBSEP IC(50) or unbound plasma concentration (C(max, u)) of the drugs in
      humans and whether the drugs caused DILI. However, all 17 of the drugs with hBSEP
      IC(50) <100 MUM and C(max, u) >0.002 MUM caused DILI. Overall, these data
      indicate that inhibition of hBSEP/rBsep correlates with the propensity of
      numerous pharmaceuticals to cause cholestatic DILI in humans and is associated
      with several of their physicochemical properties.

PMID- 21965624
TI  - Human metabolism of lapatinib, a dual kinase inhibitor: implications for
      hepatotoxicity.
AB  - Lapatinib (Tykerb, Tyverb) is an important orally active dual tyrosine kinase
      inhibitor efficacious in combination therapy for patients with progressive human
      epidermal receptor 2-overexpressing metastatic breast cancer. However, clinically
      significant liver injury, which may be associated with lapatinib metabolic
      activation, has been reported. We describe the metabolism and excretion of
      [(14)C]lapatinib in six healthy human volunteers after a single oral dose of 250
      mg and the potential relationships between metabolism and clinical
      hepatotoxicity. Overall, elimination showed high intersubject variability, with
      fecal elimination being the predominant pathway, representing a median of 92% of
      the dose with lapatinib as the largest component (approximate median 27% of the
      dose). In plasma, approximately 50% of the observed radioactivity was attributed
      to metabolites. Analysis of a 4-h pooled plasma extract identified seven
      metabolites related by an N- and alpha-carbon oxidation cascade. Fecal
      metabolites derived from three prominent pathways: N- and alpha-carbon oxidation,
      fluorobenzyl oxidative cleavage, and hydroxypyridine formation. Several of the
      lapatinib metabolites can undoubtedly be linked to reactive species such as
      aldehydes or quinone imines. In addition to the contribution of these potentially
      reactive metabolites as suspects in clinical liver injury, the role of other
      disposition factors, including interaction with drug transporters,
      pharmacogenetics, or magnitude of the therapeutic dose, should not be discounted.

PMID- 21965625
TI  - Cohort analysis finds that the proportion of people who meet high risk criteria
      for colorectal, breast or prostate cancer screening based on family history
      increases between age 30 and 50.

PMID- 21965626
TI  - Muscle atrophy; more than one string to MuRF1's bow?

PMID- 21965627
TI  - Loitering in the shadows: the cardiovascular implications of vitamin D during
      development.

PMID- 21965628
TI  - Old men still have the skeletal muscle contractile function to get up and go even
      after they have had their leg in a cast.

PMID- 21965629
TI  - ANO1-ther brick in the wall--role of Ca2+-activated Cl- channels of interstitial
      cells of Cajal in cholinergic motor control of gastrointestinal smooth muscle.

PMID- 21965630
TI  - Should Willy Wonka have been a sports nutritionist?

PMID- 21965631
TI  - A shortcut to a skeletal muscle DHPR knock-in?

PMID- 21965632
TI  - N- and O-linked glycosylation coordinate cell-surface localization of a cardiac
      potassium channel.

PMID- 21965633
TI  - What happens if you pose the wrong questions?

PMID- 21965635
TI  - Analysis of the validation status of quality of life and functional disability
      measures in pulmonary arterial hypertension related to systemic sclerosis:
      results of a systematic literature analysis by the Expert Panel on Outcomes
      Measures in Pulmonary Arterial Hypertension related to Systemic Sclerosis
      (EPOSS).
AB  - OBJECTIVE: We aimed to assess the current validity status of the Health
      Assessment Questionnaire-Disability Index (HAQ-DI) and the 36-item Medical
      Outcomes Study Short Form Health Survey (SF-36). METHODS: Studies using HAQ-DI
      and/or SF-36 in patients with pulmonary arterial hypertension (PAH) associated
      with systemic sclerosis (PAH-SSc) were identified through a systematic literature
      review and assessed according to the Outcome Measures in Rheumatology Clinical
      Trials (OMERACT) consensus group criteria. RESULTS: Both HAQ-DI and SF-36 were
      considered credible (having face validity) and feasible. Based on expert opinion,
      neither HAQ-DI nor SF-36 was specific for PAH-SSc since their results may be
      influenced by other aspects of SSc (judged "unclear" with respect to the content
      validity criterion). In the overall SSc population, there was significant albeit
      weak correlation between physical component SF-36 scores and pulmonary artery
      systolic pressure (PASP) by echocardiography (Kendall tau b = -0.2, p < 0.01).
      Although HAQ-DI also correlated with PASP by echocardiography, there were no
      significant correlations in SSc patients with PAH proven by right heart
      catheterization between changes in HAQ-DI over time and changes in other PAH
      measures including 6-min walk distance (r = -0.04, p = 0.86), expert global
      assessment (r = 0.06, p = 0.97), and New York Heart Association functional class
      (r = 0.38, p = 0.39), indicating lack of construct validity for HAQ-DI in PAH
      SSc. No studies enabling assessment of criterion validity or discrimination of
      HAQ-DI or SF-36 in PAH-SSc could be identified. CONCLUSION: Further validation of
      HAQ and SF-36 in PAH-SSc is needed. Alternatively, more specific assessments for
      functional disability or quality of life in PAH-SSc might be required.

PMID- 21965637
TI  - The role of tumor necrosis factor-alpha promoter genetic variation in Takayasu
      arteritis susceptibility and medical treatment.
AB  - OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional
      proinflammatory cytokine that influences the pathogenesis of Takayasu arteritis
      (TA). There is still no evidence of the relationship between TNF-alpha gene
      promoter polymorphisms and TA. We examined whether variations in the TNF-alpha
      promoter region may lead to TA susceptibility and disease progression. METHODS:
      Five TNF-alpha gene promoter polymorphisms (-238G/A, -308G/A, -857C/T, -863C/A,
      and -1031C/T) were analyzed in 110 Chinese Han patients with TA, with a control
      group of 362 unrelated healthy individuals. Genotypes of TNF-alpha gene promoter
      polymorphisms were identified by direct sequencing. TNF-alpha plasma
      concentrations were determined by ELISA. RESULTS: Our results indicated that the
      frequency of the -863A allele was significantly lower in the patients with TA
      than in the controls (18.2% vs 25.7%; p = 0.011), but the significance was lost
      after Bonferroni correction (p(c) = 0.055). The frequency of -863CA/AA genotypes
      was significantly lower in the patients with refractory TA than in those with the
      863CC genotype (22.4% vs 44.2%; p(c) < 0.01). The frequency of the GGCCT
      haplotype was significantly higher in patients than in the controls, while the
      frequencies of GGCAT and GGCCC haplotypes were significantly lower in patients
      than in controls. The plasma TNF-alpha concentrations were significantly lower in
      the subjects carrying the -863A allele than in those without. Patients with
      active TA had a significant increase in plasma levels of TNF-alpha compared with
      remission patients and the control group. CONCLUSION: Polymorphisms of the TNF
      alpha promoter are not associated with TA in the Chinese Han population. The A
      allele of the -863C/A polymorphism is associated with decreased TNF-alpha
      expression, which might affect medical treatment.

PMID- 21965636
TI  - An international, randomized, double-blind, placebo-controlled, phase III trial
      of pregabalin monotherapy in treatment of patients with fibromyalgia.
AB  - OBJECTIVE: To evaluate the efficacy and safety of pregabalin monotherapy versus
      placebo for symptomatic pain relief and improvement of patient global assessment
      in patients with fibromyalgia (FM) enrolled from countries outside the United
      States. METHODS: This international, multicenter, double-blind, placebo
      controlled trial randomly assigned 747 patients with FM to placebo or 300, 450,
      or 600 mg/day pregabalin twice daily for 14 weeks. Primary efficacy measures were
      endpoint mean pain scores and Patient Global Impression of Change (PGIC).
      Secondary outcomes included assessments of sleep and function. RESULTS: Patients
      in the 450 mg/day pregabalin group showed significant improvements versus placebo
      in endpoint mean pain score (-0.56; p = 0.0132), PGIC (73% improved vs 56%
      placebo; p = 0.0017), and function [Fibromyalgia Impact Questionnaire (FIQ) total
      score -5.85; p = 0.0012]. PGIC was also significant for 600 mg/day pregabalin
      (69% improved; p = 0.0227). Results for these endpoints were nonsignificant for
      pregabalin at 300 mg/day and for pain and FIQ score at 600 mg/day. Early onset of
      pain relief was seen, with separation from placebo detected by Week 1 in all
      pregabalin groups. All pregabalin doses demonstrated superiority to placebo on
      the Medical Outcomes Study-Sleep Scale Sleep Disturbance subscale and the Sleep
      Quality diary. Dizziness and somnolence were the most frequently reported adverse
      events. CONCLUSION: Pregabalin demonstrated modest efficacy in pain, global
      assessment, and function in FM at 450 mg/day, and improved sleep across all dose
      levels, but it did not provide consistent evidence of benefit at 300 and 600
      mg/day in this study. Pregabalin was generally well tolerated for the treatment
      of FM. (Clinical trial registry NCT00333866).

PMID- 21965638
TI  - Tricuspid annular plane systolic excursion is a robust outcome measure in
      systemic sclerosis-associated pulmonary arterial hypertension.
AB  - OBJECTIVE: The tricuspid annular plane systolic excursion (TAPSE) strongly
      reflects right ventricular (RV) function and predicts survival in idiopathic
      pulmonary arterial hypertension (PAH). But its role in systemic sclerosis (SSc)
      associated PAH has not been established. Our objective was to validate the TAPSE
      in the assessment of RV function and prediction of survival in SSc-PAH. METHODS:
      Fifty consecutive patients with SSc-PAH who underwent echocardiography with TAPSE
      measurement within 1 h of clinically indicated right heart catheterization were
      followed prospectively. The relationship between TAPSE and measures of RV
      function and measures of survival was assessed. RESULTS: The majority of the
      cohort were women in New York Heart Association class III/IV with severe PAH
      (mean cardiac index 2.4 +/- 0.8 l/min/m(2)). RV function was significantly
      impaired (mean cardiac index 2.1 +/- 0.7 vs 2.9 +/- 0.8 l/min/m(2); p < 0.01) and
      RV afterload was significantly greater (mean pulmonary vascular resistance 11.1
      +/- 5.1 vs 5.8 +/- 2.5 Wood units; p < 0.01) in subjects with a TAPSE <= 1.7 cm.
      The proportion surviving in the low TAPSE group was significantly lower [0.56
      (95% CI 0.37-0.71) and 0.46 (95% CI 0.28-0.62) vs 0.87 (95% CI 0.55-0.96) and
      0.79 (95% CI 0.49-0.93), 1- and 2-year survival, respectively]. TAPSE <= 1.7 cm
      conferred a nearly 4-fold increased risk of death (HR 3.81, 95% CI 1.31-11.1, p <
      0.01). CONCLUSION: TAPSE is a robust measure of RV function and strongly predicts
      survival in patients with PAH-SSc. Future studies are needed to identify the
      responsiveness of TAPSE to PAH-specific therapy and to assess its diagnostic
      utility in PAH-SSc.

PMID- 21965639
TI  - Effects of changing from oral to subcutaneous methotrexate on red blood cell
      methotrexate polyglutamate concentrations and disease activity in patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: To determine the effects of changing from oral to subcutaneous (SC)
      methotrexate (MTX) in patients with rheumatoid arthritis (RA) on red blood cell
      MTX polyglutamate (RBC MTXGlu(n)) concentrations, disease activity, and adverse
      effects. METHODS: Thirty patients were changed from oral to SC MTX. Trough RBC
      MTXGlu(n) concentrations were measured for 24 weeks and concentrations fitted to
      a first-order accumulation model. Disease activity was assessed by 28-joint
      Disease Activity Score (DAS28). RESULTS: MTXGlu(3), MTXGlu(4), and MTXGlu(5)
      concentrations, but not MTXGlu(1) and MTXGlu(2), increased significantly over 24
      weeks, reaching 90% of new steady-state concentrations by about 40 weeks. A
      decrease in DAS28 was associated with increased RBC MTXGlu(5) (p = 0.035) and RBC
      MTXGlu(3-5) (p = 0.032). No change in adverse effect frequency occurred.
      CONCLUSION: Changing to SC MTX results in increased long-chain MTXGlu(n).
      However, it takes at least 6 months for RBC steady-state concentrations to be
      achieved. Increased long-chain MTXGlu(n) concentrations were significantly
      associated with reduced disease activity.

PMID- 21965640
TI  - Magnetic resonance imaging bone edema is not a major feature of gout unless there
      is concomitant osteomyelitis: 10-year findings from a high-prevalence population.
AB  - OBJECTIVE: Magnetic resonance imaging (MRI) is commonly used in autoimmune
      inflammatory arthritis to define disease activity and damage, but its role in
      gout remains unclear. The aim of our study was to identify and describe the MRI
      features of gout. METHODS: Over a 10-year period we identified patients with gout
      who underwent MRI scanning of the hands or feet. Scans were reviewed for
      erosions, synovitis, tenosynovitis, tendinosis, bone edema, and tophi by a
      musculoskeletal radiologist and 2 rheumatologists in a blinded manner. MRI
      features in patients with uncomplicated gout were compared with features where
      concomitant osteomyelitis was diagnosed. RESULTS: A total of 47 patients with
      gout (51 scans) were included: 33 (70%) had uncomplicated gout and 14 (30%) had
      gout complicated by osteomyelitis. MRI features included tophi in 36 scans (71%),
      erosions in 35 (69%), bone edema in 27 (53%), synovitis in 15 (29%),
      tenosynovitis in 8 (16%), and tendinosis in 2 (4%). Uncomplicated gout and gout
      plus osteomyelitis did not differ for most MRI features. However, "severe bone
      marrow edema" was much more common in gout plus osteomyelitis, occurring in 14/15
      scans (93%) compared with 3/36 scans (8%) in uncomplicated gout (OR 154.0, 95% CI
      14.7-1612, p < 0.0001). Sensitivity and specificity of "severe bone edema" for
      concomitant osteomyelitis were 0.93 (95% CI 0.68-0.99) and 0.92 (95% CI 0.78
      0.98), respectively. CONCLUSION: MRI reveals that gout affects the joints, bones,
      and tendons. Bone edema in patients with chronic tophaceous gout is frequently
      mild and this contrasts with the "severe bone edema" observed in patients with
      concomitant osteomyelitis.

PMID- 21965641
TI  - Relationship between smoking and patient-reported measures of disease outcome in
      ankylosing spondylitis.
AB  - OBJECTIVE: To investigate the relationship between smoking and disease activity,
      pain, function, and quality of life in patients with ankylosing spondylitis (AS).
      METHODS: Patients with AS (n = 612) from areas across the United Kingdom took
      part in a cross-sectional postal survey. Patient-reported outcome measures
      including the Bath AS Disease Activity Index, the Bath AS Functional Index
      (BASFI), a numerical rating scale (NRS) of pain, the AS quality of life
      questionnaire (ASQoL), and the evaluation of AS quality of life measures (EASi
      QoL) were analyzed in terms of smoking status and relationship with pack-year
      history. The influence of potential confounding factors [age, sex, disease
      duration, and social deprivation (Townsend Index)] were tested in multivariate
      logistic regression analyses. RESULTS: Median scores of BASFI, pain NRS, ASQoL,
      and the 4 EASi-QoL domains were all higher in the group that had ever smoked
      compared to those who had never smoked (p < 0.0001, p = 0.04, p = 0.003, p <
      0.02, respectively). In stepwise multivariate logistic regression analyses, high
      disease activity and more severe pain were associated primarily with current
      smoking, disease duration, and Townsend Index score, while decreased function and
      poor quality of life measures were associated more closely with increasing pack
      year history, disease duration, and Townsend Index score. These associations were
      independent of age and sex. CONCLUSION: Smoking has a dose-dependent relationship
      with measures of disease severity in AS. The association with increased disease
      activity, decreased function, and poor quality of life in smokers was independent
      of age, sex, deprivation level, and disease duration.

PMID- 21965642
TI  - The influence of the definition of patient global assessment in assessment of
      disease activity according to the Disease Activity Score (DAS28) in rheumatoid
      arthritis.
AB  - OBJECTIVE: Patient global assessment (PGA) is one of the 4 items included in the
      Disease Activity Score (DAS28) for evaluation of activity of rheumatoid arthritis
      (RA). We studied the influence of the use of 3 different techniques of PGA on the
      assessment of disease activity. METHODS: We evaluated 3 different DAS28 according
      to the technique of PGA in 108 patients with active RA before and after 12 weeks
      of etanercept therapy. RESULTS: The reliability (intraclass coefficient of
      correlation) between screening and baseline was very high and similar for the 3
      DAS28. The percentage of patients in the different states of disease (from
      remission to higher disease activity) and the sensitivity to change across the 3
      DAS28 scales were very similar. CONCLUSION: The different techniques of
      collection of PGA to be included in the DAS calculation yield similar results.
      However, an accepted, unequivocal technique should be encouraged in order to
      reduce heterogeneity in scoring DAS among patients with RA.

PMID- 21965643
TI  - Measuring pain in systemic sclerosis: comparison of the short-form McGill Pain
      Questionnaire versus a single-item measure of pain.
AB  - OBJECTIVE: Studies of pain in systemic sclerosis (SSc) have used a variety of
      measures, including single-item measures and the 15-item short-form McGill Pain
      Questionnaire (MPQ-SF). The objective of our study was to compare the performance
      of the MPQ-SF to a single-item pain numerical rating scale (NRS) and determine
      whether the MPQ-SF effectively differentiates between sensory and affective
      components of pain in SSc. METHODS: A cross-sectional, multicenter study of 1091
      patients from the Canadian Scleroderma Research Group Registry who completed the
      MPQ-SF and pain NRS. Correlations of MPQ-SF total scores and pain NRS scores with
      relevant outcome measures (disability, quality of life, depressive symptoms) were
      compared. To assess whether the MPQ-SF differentiated between sensory and
      affective factors, confirmatory factor analysis modeling was used, and
      correlations of sensory and affective factor scores with other outcome measures
      were compared. RESULTS: MPQ-SF total score and the pain NRS correlated similarly
      with other outcome measures, as did the sensory and affective scores. MPQ-SF
      sensory and affective factors were highly correlated (0.92), and a single-factor
      model fit as well as a 2-factor (sensory and affective) model. CONCLUSION: The
      substantial overlap between sensory and affective subscales of the MPQ-SF and the
      similarity of the MPQ-SF and NRS pain measures compared to other patient-reported
      outcomes suggest that the 15-item MPQ-SF does not provide tangible advantages
      compared to the single-item pain NRS. These findings support recommendations to
      use a single-item NRS pain measure in SSc as it is less burdensome to patients
      than the MPQ-SF.

PMID- 21965644
TI  - Validating the 28-tender joint count using item response theory.
AB  - OBJECTIVE: To examine the construct validity of the 28-tender joint count (TJC
      28) using item response theory (IRT)-based methods. METHODS: A total of 457
      patients with early stage rheumatoid arthritis (RA) were included. Internal
      construct validity of the TJC-28 was evaluated by determining whether the TJC-28
      fit a 2-measure logistic IRT model. As well, we tested whether the discrimination
      and difficulty parameters of the joints properly reflected the known left-right
      symmetry of joint involvement. External validity was evaluated by correlations
      with other established measures of disease activity, including pain, disability,
      general health, erythrocyte sedimentation rate (ESR), and the 28-swollen joint
      count. RESULTS: The TJC-28 showed a good fit with the 2-parameter logistic model,
      with no relevant differential item functioning across sex, age, and time and with
      excellent reliability. The 28 joints covered a reasonable range of disease
      activity, even though they were mainly targeted at patients with moderate or high
      disease activity levels. The joint parameters reflected the left-right symmetry
      of joint involvement for all pairs of joints except one. All disease activity
      measures, except ESR, were significantly correlated with the TJC-28. Most
      correlations were of the expected magnitude. CONCLUSION: The TJC-28 showed good
      internal and acceptable external construct validity for patients with early-stage
      RA. The IRT analyses did point to some potential limitations of the instrument, a
      major problem being its limited measurement range. Future research should examine
      whether instrument modifications might lead to a more robust assessment of
      disease activity in patients with RA.

PMID- 21965645
TI  - Should anti-citrullinated protein antibody and rheumatoid factor status be
      reassessed during the first year of followup in recent-onset arthritis? A
      longitudinal study.
AB  - OBJECTIVE: Presence and levels of antibodies contribute to the classification of
      rheumatoid arthritis. We investigated the longitudinal course of anti
      citrullinated protein antibodies (ACPA) and immunoglobin M (IgM) rheumatoid
      factor (RF) during the first year after arthritis onset in patients with very
      short disease duration. METHODS: Patients (aged 18-75 years) with >= 1 swollen
      joint of <= 16 weeks' duration had assessments of ACPA (2nd generation anti
      cyclic citrullinated peptide antibodies, anti-CCP2) and IgM RF at inclusion and
      after 3, 6, and 12 months. Frequencies of seroconversions (negative to positive
      and vice versa) and changes in antibody levels during followup were determined.
      RESULTS: A total of 281 early arthritis patients (median duration of joint
      swelling 32 days, 14.2% ACPA positives, 12.8% IgM RF positives) with 978
      longitudinally collected serum samples were included. Only 5 patients (1.8%)
      negative for both antibodies at baseline turned antibody-positive during
      followup, while 9 antibody-positive patients (3.2%) turned antibody-negative.
      ACPA was more stable than RF regarding both status and levels. CONCLUSION:
      Antibody status (ACPA/RF) is a stable phenotype in very early arthritis, as
      seroconversion was only found in 5% of patients. Repeated measurement of ACPA or
      RF during the first year after onset of arthritis does not offer major additional
      information.

PMID- 21965647
TI  - A nonsynonymous functional variant of the ITGAM gene is not involved in biopsy
      proven giant cell arteritis.
AB  - OBJECTIVE: To investigate whether a functional integrin alpha M (ITGAM) variant
      is involved in susceptibility to and clinical manifestations of giant cell
      arteritis (GCA). METHODS: A Spanish cohort of 437 white patients with biopsy
      proven GCA and 1388 healthy controls were genotyped using the TaqMan allele
      discrimination technology. RESULTS: No association was observed between ITGAM
      rs1143679 and GCA (p = 0.80, OR 0.97). Similarly, subphenotype analyses did not
      yield significant differences between the case subgroups and the control set or
      between GCA patients with or without the main specific features of GCA.
      CONCLUSION: Our results suggest that the ITGAM rs1143679 variant does not play an
      important role in the pathophysiology of GCA.

PMID- 21965646
TI  - Safety and effectiveness of rituximab in patients with rheumatoid arthritis
      following an inadequate response to 1 prior tumor necrosis factor inhibitor: the
      RESET Trial.
AB  - OBJECTIVE: To evaluate the safety and effectiveness of rituximab (RTX) in
      combination with methotrexate in patients with active rheumatoid arthritis (RA)
      after failure of a single tumor necrosis factor-alpha (TNF-alpha) inhibitor.
      Changes in patient-reported outcomes after primary treatment or retreatment with
      RTX and factors determining retreatment in clinical practice were also evaluated.
      METHODS: In this phase 3b open-label, multicenter trial, patients received 2 slow
      infusions of RTX 1000 mg 14 days apart after premedication (primary treatment).
      Patients with a clinically relevant response could receive retreatment between 24
      and 48 weeks. The primary endpoint was evaluation of safety. Secondary outcomes
      were safety of retreatment, effectiveness of primary treatment and retreatment,
      and changes in patient-reported outcomes after primary treatment or retreatment.
      RESULTS: Of 120 patients enrolled at 36 centers and receiving primary RTX
      treatment, 77 received retreatment, 112 completed the 24-week primary treatment
      period, and 25 completed the 48-week primary treatment and retreatment period
      following a single course of RTX. The most common adverse events were mild to
      moderate nausea, vomiting, nasopharyngitis, and headache. No infections or
      infusion reactions were considered life-threatening. At 24 weeks, 58%, 27%, and
      7% of patients achieved American College of Rheumatology 20, 50, and 70
      improvements, respectively, and similar improvements were seen after retreatment.
      CONCLUSION: RTX was well tolerated, with a low incidence of infusion reactions
      and infections. Efficacy results, including enhanced response in rheumatoid
      factor-positive patients, were comparable to those reported in the literature.
      Based on its efficacy and safety profile and retreatment schedule, RTX is an
      attractive treatment option for patients that have not responded to a single TNF
      alpha inhibitor.

PMID- 21965648
TI  - Anti-Ro/SSA antibodies are an independent factor associated with an insufficient
      response to tumor necrosis factor inhibitors in patients with rheumatoid
      arthritis.
AB  - OBJECTIVE: To study the significance of anti-Ro/SSA antibodies (anti-Ro) in the
      clinical response to tumor necrosis factor (TNF) inhibitors in patients with
      rheumatoid arthritis (RA). METHODS: The clinical responses of a cohort of 190
      patients with RA who were treated with infliximab, etanercept, or adalimumab (n =
      112, 64, and 14, respectively) as the first biologics were examined using the
      Disease Activity Score in 28 joints (DAS28) at 24 weeks and the discontinuation
      rate at 56 weeks. The baseline characteristics of responders and the
      nonresponders were compared. The clinical response was compared between anti-Ro
      negative and -positive patients. The factors associated with the inefficiency of
      TNF inhibitors were estimated with a multivariable logistic regression analysis.
      RESULTS: The positive rate of anti-Ro was significantly higher in patients with
      no European League Against Rheumatism (EULAR) response at 24 weeks (OR 3.64, 95%
      CI 1.45-9.01, p = 0.003). In anti-Ro-positive patients, a moderate or good EULAR
      response rate was significantly lower with a sustaining higher median DAS28 (p =
      0.006), and this difference was greater among infliximab-treated patients. The
      discontinuation rate for TNF inhibitors due to inefficacy at 56 weeks was also
      higher in anti-Ro-positive patients (OR 4.68, 95% CI 1.82-11.99, p = 0.0005), and
      75% of these patients received infliximab. The presence of anti-Ro was strongly
      associated with no EULAR response at 24 weeks and a higher discontinuation rate
      of TNF inhibitors by 56 weeks (OR 5.22, 95% CI 1.75-15.57, p = 0.003 and OR
      10.18, 95% CI 2.18-49.56, p = 0.003). CONCLUSION: The presence of anti-Ro might
      be related to the lesser clinical response to infliximab compared to other TNF
      inhibitors, suggesting that the presence of anti-Ro should be considered when
      choosing the appropriate biologics for patients with RA.

PMID- 21965649
TI  - Evidence for PTPN22 R620W polymorphism as the sole common risk variant for
      rheumatoid arthritis in the 1p13.2 region.
AB  - OBJECTIVE: The PTPN22 rs2476601 genetic variant has been associated with
      rheumatoid arthritis (RA) and other autoimmune diseases. Some reports suggest
      that this single-nucleotide polymorphism (SNP) may not be the only causal variant
      in the region of PTPN22. Our aim was to identify new independent RA-associated
      common gene variants in the PTPN22 region. METHODS: We analyzed Wellcome Trust
      Case-Control Consortium genome-wide association study data for associations in
      the 397.2 kb PTPN22 region and selected 9 associated SNP (with p < 5 * 10(-3))
      for replication and dependence analysis. The replication cohorts comprised 2857
      patients with RA and 2994 controls from Spain, Netherlands, and Norway. RESULTS:
      We found that 6 of the 9 selected SNP were associated in the Spanish cohort. Of
      these, 4 were also associated in the Dutch and Norwegian cohorts, and all 6 were
      associated with RA in the combined analysis. Conditional analyses showed that
      none of these associations was independent of rs2476601. CONCLUSION: The SNP
      rs2476601 located in the PTPN22 gene is the sole common genetic variant
      associated with RA in the 1p13.2 region, suggesting that neighbor genes of PTPN22
      do not have a major influence in RA.

PMID- 21965650
TI  - Predictors of chronic kidney disease in Korean patients with lupus nephritis.
AB  - OBJECTIVE: Since chronic kidney disease (CKD) is closely associated with
      cardiovascular disease and mortality as well as endstage renal disease,
      prediction of progressive CKD is a clinically important issue. We investigated
      the independent risk factors for the development of CKD in patients with lupus
      nephritis (LN). METHODS: The cohort included 322 Korean patients diagnosed with
      LN between 1985 and 2010. We retrospectively analyzed the clinical and laboratory
      indices, treatment response, the final renal function, and the biopsy findings.
      The timing and cumulative risk of developing CKD were identified by Kaplan-Meier
      methods. The independent risk factors for developing CKD were examined by
      univariate and multivariate Cox proportional hazards regression analyses.
      RESULTS: The median followup time after the diagnosis of LN was 84 months. CKD
      occurs in 22% of the patients within 10 years after the diagnosis of LN. The
      probability of developing CKD was significantly associated with the onset time of
      LN (delayed-onset LN vs initial-onset LN; HR 2.904, p = 0.003), deteriorated
      renal function [an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73
      m(2) body surface area] at the onset of LN (HR 7.458, p < 0.001), relapse of LN
      after achieving remission (HR 2.806, p = 0.029), and resistance to induction
      therapy (HR 8.120, p < 0.001). CONCLUSION: Our results demonstrate that delayed
      onset LN, a decreased eGFR at the time of LN onset, and the failure to achieve a
      sustained remission are predictors for the development of CKD in Korean patients
      with LN.

PMID- 21965651
TI  - Red and problematic green phylogenetic signals among thousands of nuclear genes
      from the photosynthetic and apicomplexa-related Chromera velia.
AB  - The photosynthetic and basal apicomplexan Chromera velia was recently described,
      expanding the membership of this otherwise nonphotosynthetic group of parasite
      protists. Apicomplexans are alveolates with secondary plastids of red algal
      origin, but the evolutionary history of their nuclear genes is still actively
      discussed. Using deep sequencing of expressed genes, we investigated the
      phylogenetic affinities of a stringent filtered set of 3,151 expressed sequence
      tag-contigs by generating clusters with eukaryotic homologs and constructing
      phylogenetic trees and networks. The phylogenetic positioning of this alveolate
      alga was determined and sets of phyla-specific proteins extracted. Phylogenetic
      trees provided conflicting signals, with 444 trees grouping C. velia with the
      apicomplexans but 354 trees grouping C. velia with the alveolate oyster pathogen
      Perkinsus marinus, the latter signal being reinforced from the analysis of shared
      genes and overall sequence similarity. Among the 513 C. velia nuclear genes that
      reflect a photosynthetic ancestry and for which nuclear homologs were available
      both from red and green lineages, 263 indicated a red photosynthetic ancestry,
      whereas 250 indicated a green photosynthetic ancestry. The same 1:1 signal ratio
      was found among the putative 255 nuclear-encoded plastid proteins identified.
      This finding of red and green signals for the alveolate mirrors the result
      observed in the heterokont lineage and supports a common but not necessarily
      single origin for the plastid in heterokonts and alveolates. The inference of
      green endosymbiosis preceding red plastid acquisition in these lineages leads to
      worryingly complicated evolutionary scenarios, prompting the search for other
      explanations for the green phylogenetic signal and the amount of hosts involved.

PMID- 21965652
TI  - Phosphorylation of MCM3 protein by cyclin E/cyclin-dependent kinase 2 (Cdk2)
      regulates its function in cell cycle.
AB  - MCM2-7 proteins form a stable heterohexamer with DNA helicase activity
      functioning in the DNA replication of eukaryotic cells. The MCM2-7 complex is
      loaded onto chromatin in a cell cycle-dependent manner. The phosphorylation of
      MCM2-7 proteins contributes to the formation of the MCM2-7 complex. However, the
      regulation of specific MCM phosphorylation still needs to be elucidated. In this
      study, we demonstrate that MCM3 is a substrate of cyclin E/Cdk2 and can be
      phosphorylated by cyclin E/Cdk2 at Thr-722. We find that the MCM3 T722A mutant
      binds chromatin much less efficiently when compared with wild type MCM3,
      suggesting that this phosphorylation site is involved in MCM3 loading onto
      chromatin. Interestingly, overexpression of MCM3, but not MCM3 T722A mutant,
      inhibits the S phase entry, whereas it does not affect the exit from mitosis.
      Knockdown of MCM3 does not affect S phase entry and progression, indicating that
      a small fraction of MCM3 is sufficient for normal S phase completion. These
      results suggest that excess accumulation of MCM3 protein onto chromatin may
      inhibit DNA replication. Other studies indicate that excess of MCM3 up-regulates
      the phosphorylation of CHK1 Ser-345 and CDK2 Thr-14. These data reveal that the
      phosphorylation of MCM3 contributes to its function in controlling the S phase
      checkpoint of cell cycle in addition to the regulation of formation of the MCM2-7
      complex.

PMID- 21965653
TI  - E3 ligases determine ubiquitination site and conjugate type by enforcing
      specificity on E2 enzymes.
AB  - Ubiquitin-conjugating enzymes (E2s) have a dominant role in determining which of
      the seven lysine residues of ubiquitin is used for polyubiquitination. Here we
      show that tethering of a substrate to an E2 enzyme in the absence of an E3
      ubiquitin ligase is sufficient to promote its ubiquitination, whereas the type of
      the ubiquitin conjugates and the identity of the target lysine on the substrate
      are promiscuous. In contrast, when an E3 enzyme is introduced, a clear decision
      between mono- and polyubiquitination is made, and the conjugation type as well as
      the identity of the target lysine residue on the substrate becomes highly
      specific. These features of the E3 can be further regulated by auxiliary factors
      as exemplified by MDMX (Murine Double Minute X). In fact, we show that this
      interactor reconfigures MDM2-dependent ubiquitination of p53. Based on several
      model systems, we propose that although interaction with an E2 is sufficient to
      promote substrate ubiquitination the E3 molds the reaction into a specific,
      physiologically relevant protein modification.

PMID- 21965654
TI  - Membrane anchoring of aminoacyl-tRNA synthetases by convergent acquisition of a
      novel protein domain.
AB  - Four distinct aminoacyl-tRNA synthetases (aaRSs) found in some cyanobacterial
      species contain a novel protein domain that bears two putative transmembrane
      helices. This CAAD domain is present in glutamyl-, isoleucyl-, leucyl-, and valyl
      tRNA synthetases, the latter of which has probably recruited the domain more than
      once during evolution. Deleting the CAAD domain from the valyl-tRNA synthetase of
      Anabaena sp. PCC 7120 did not significantly modify the catalytic properties of
      this enzyme, suggesting that it does not participate in its canonical tRNA
      charging function. Multiple lines of evidence suggest that the function of the
      CAAD domain is structural, mediating the membrane anchorage of the enzyme,
      although membrane localization of aaRSs has not previously been described in any
      living organism. Synthetases containing the CAAD domain were localized in the
      intracytoplasmic thylakoid membranes of cyanobacteria and were largely absent
      from the plasma membrane. The CAAD domain was necessary and apparently sufficient
      for protein targeting to membranes. Moreover, localization of aaRSs in thylakoids
      was important under nitrogen limiting conditions. In Anabaena, a multicellular
      filamentous cyanobacterium often used as a model for prokaryotic cell
      differentiation, valyl-tRNA synthetase underwent subcellular relocation at the
      cell poles during heterocyst differentiation, a process also dependent on the
      CAAD domain.

PMID- 21965655
TI  - Loss of tumor suppressor Merlin in advanced breast cancer is due to post
      translational regulation.
AB  - Unlike malignancies of the nervous system, there have been no mutations
      identified in Merlin in breast cancer. As such, the role of the tumor suppressor,
      Merlin, has not been investigated in breast cancer. We assessed Merlin expression
      in breast cancer tissues by immunohistochemistry and by real-time PCR. The
      expression of Merlin protein (assessed immunohistochemically) was significantly
      decreased in breast cancer tissues (although the transcript levels were
      comparable) simultaneous with increased expression of the tumor-promoting
      protein, osteopontin (OPN). We further demonstrate that the loss of Merlin in
      breast cancer is brought about, in part, due to OPN-initiated Akt-mediated
      phosphorylation of Merlin leading to its proteasomal degradation. Restoring
      expression of Merlin resulted in reduced malignant attributes of breast cancer,
      characterized by reduced invasion, migration, motility, and impeded tumor
      (xenograft) growth in immunocompromised mice. The possibility of developing a
      model using the relationship between OPN and Merlin was tested with a logistic
      regression model applied to immunohistochemistry data. This identified consistent
      loss of immunohistochemical expression of Merlin in breast tumor tissues. Thus,
      we demonstrate for the first time a role for Merlin in impeding breast
      malignancy, identify a novel mechanism for the loss of Merlin protein in breast
      cancer, and have developed a discriminatory model using Merlin and OPN expression
      in breast tumor tissues.

PMID- 21965656
TI  - Phosphorylation of a PDZ domain extension modulates binding affinity and
      interdomain interactions in postsynaptic density-95 (PSD-95) protein, a membrane
      associated guanylate kinase (MAGUK).
AB  - Postsynaptic density-95 is a multidomain scaffolding protein that recruits
      glutamate receptors to postsynaptic sites and facilitates signal processing and
      connection to the cytoskeleton. It is the leading member of the membrane
      associated guanylate kinase family of proteins, which are defined by the PSD
      95/Discs large/ZO-1 (PDZ)-Src homology 3 (SH3)-guanylate kinase domain sequence.
      We used NMR to show that phosphorylation of conserved tyrosine 397, which occurs
      in vivo and is located in an atypical helical extension (alpha3), initiates a
      rapid equilibrium of docked and undocked conformations. Undocking reduced ligand
      binding affinity allosterically and weakened the interaction of PDZ3 with SH3
      even though these domains are separated by a ~25-residue linker. Additional
      phosphorylation at two linker sites further disrupted the interaction,
      implicating alpha3 and the linker in tuning interdomain communication. These
      experiments revealed a novel mode of regulation by a detachable PDZ element and
      offer a first glimpse at the dynamic interaction of PDZ and SH3-guanylate kinase
      domains in membrane-associated guanylate kinases.

PMID- 21965657
TI  - The mTOR (mammalian target of rapamycin) kinase maintains integrity of mTOR
      complex 2.
AB  - In higher eukaryotes, growth factors promote anabolic processes and stimulate
      cell growth, proliferation, and survival by activation of the phosphoinositide 3
      kinase (PI3K)/Akt pathway. Deregulation of PI3K/Akt signaling is linked to human
      diseases, including cancer and metabolic disorders. The PI3K-dependent signaling
      kinase complex mTORC2 (mammalian target of rapamycin complex 2) has been defined
      as the regulatory Ser-473 kinase of Akt. The regulation of mTORC2 remains very
      poorly characterized. We have reconstituted mTORC2 by its assembly in vitro or by
      co-expression its four essential components (rictor, SIN1, mTOR, mLST8). We show
      that the functional mTOR kinase domain is required for the mTORC2 activity as the
      Ser-473 kinase of Akt. We also found that mTOR by phosphorylation of SIN1
      prevents its lysosomal degradation. Thus, the kinase domain of mTOR is required
      for the functional activity of mTORC2, and it controls integrity of mTORC2 by
      maintaining the protein stability of SIN1.

PMID- 21965658
TI  - Mutagenesis of surfactant protein D informed by evolution and x-ray
      crystallography enhances defenses against influenza A virus in vivo.
AB  - The recognition of influenza A virus (IAV) by surfactant protein D (SP-D) is
      mediated by interactions between the SP-D carbohydrate recognition domains (CRD)
      and glycans displayed on envelope glycoproteins. Although native human SP-D shows
      potent antiviral and aggregating activity, trimeric recombinant neck+CRDs (NCRDs)
      show little or no capacity to influence IAV infection. A mutant trimeric NCRD,
      D325A/R343V, showed marked hemagglutination inhibition and viral neutralization,
      with viral aggregation and aggregation-dependent viral uptake by neutrophils.
      D325A/R343V exhibited glucose-sensitive binding to Phil82 hemagglutinin trimer
      (HA) by surface plasmon resonance. By contrast, there was very low binding to the
      HA trimer from another virus (PR8) that lacks glycans on the HA head. Mass
      spectrometry demonstrated the presence of high mannose glycans on the Phil82 HA
      at positions known to contribute to IAV binding. Molecular modeling predicted an
      enhanced capacity for bridging interactions between HA glycans and D325A/R343V.
      Finally, the trimeric D325A/R343V NCRD decreased morbidity and increased viral
      clearance in a murine model of IAV infection using a reassortant A/WSN/33 virus
      with a more heavily glycosylated HA. The combined data support a model in which
      altered binding by a truncated mutant SP-D to IAV HA glycans facilitates viral
      aggregation, leading to significant viral neutralization in vitro and in vivo.
      These studies demonstrate the potential utility of homology modeling and protein
      structure analysis for engineering effective collectin antivirals as in vivo
      therapeutics.

PMID- 21965659
TI  - Three lysine residues in the common beta chain of the interleukin-5 receptor are
      required for Janus kinase (JAK)-dependent receptor ubiquitination, endocytosis,
      and signaling.
AB  - Eosinophils are multifunctional leukocytes implicated in the pathogenesis of
      numerous inflammatory diseases including allergic asthma and hypereosinophilic
      syndrome. Eosinophil physiology is critically dependent on IL-5 and the IL-5
      receptor (IL-5R), composed of a ligand binding alpha chain (IL-5Ralpha), and a
      common beta chain, betac. Previously, we demonstrated that the betac cytoplasmic
      tail is ubiquitinated and degraded by proteasomes following IL-5 stimulation.
      However, a complete understanding of the role of betac ubiquitination in IL-5R
      biology is currently lacking. By using a well established, stably transduced
      HEK293 cell model system, we show here that in the absence of ubiquitination,
      betac subcellular localization, IL-5-induced endocytosis, turnover, and IL-5R
      signaling were significantly impaired. Whereas ubiquitinated IL-5Rs internalized
      into trafficking endosomes for their degradation, ubiquitination-deficient IL-5Rs
      accumulated on the cell surface and displayed blunted signaling even after IL-5
      stimulation. Importantly, we identified a cluster of three membrane-proximal
      betac lysine residues (Lys(457), Lys(461), and Lys(467)) whose presence was
      required for both JAK1/2 binding to betac and receptor ubiquitination. These
      findings establish that JAK kinase binding to betac requires the presence of
      three critical betac lysine residues, and this binding event is essential for
      receptor ubiquitination, endocytosis, and signaling.

PMID- 21965660
TI  - Plant cap-binding complexes eukaryotic initiation factors eIF4F and eIFISO4F:
      molecular specificity of subunit binding.
AB  - The initiation of translation in eukaryotes requires a suite of eIFs that include
      the cap-binding complex, eIF4F. eIF4F is comprised of the subunits eIF4G and
      eIF4E and often the helicase, eIF4A. The eIF4G subunit serves as an assembly
      point for other initiation factors, whereas eIF4E binds to the 7-methyl guanosine
      cap of mRNA. Plants have an isozyme form of eIF4F (eIFiso4F) with comparable
      subunits, eIFiso4E and eIFiso4G. Plant eIF4A is very loosely associated with the
      plant cap-binding complexes. The specificity of interaction of the individual
      subunits of the two complexes was previously unknown. To address this issue,
      mixed complexes (eIF4E-eIFiso4G or eIFiso4E-eIF4G) were expressed and purified
      from Escherichia coli for biochemical analysis. The activity of the mixed
      complexes in in vitro translation assays correlated with the large subunit of the
      respective correct complex. These results suggest that the eIF4G or eIFiso4G
      subunits influence translational efficiency more than the cap-binding subunits.
      The translation assays also showed varying responses of the mRNA templates to
      eIF4F or eIFiso4F, suggesting that some level of mRNA discrimination is possible.
      The dissociation constants for the correct complexes have K(D) values in the
      subnanomolar range, whereas the mixed complexes were found to have K(D) values in
      the ~10 nm range. Displacement assays showed that the correct binding partner
      readily displaces the incorrect binding partner in a manner consistent with the
      difference in K(D) values. These results show molecular specificity for the
      formation of plant eIF4F and eIFiso4F complexes and suggest a role in mRNA
      discrimination during initiation of translation.

PMID- 21965661
TI  - Adaptor protein complex-2 (AP-2) and epsin-1 mediate protease-activated receptor
      1 internalization via phosphorylation- and ubiquitination-dependent sorting
      signals.
AB  - Signaling by protease-activated receptor-1 (PAR1), a G protein-coupled receptor
      (GPCR) for thrombin, is regulated by desensitization and internalization. PAR1
      desensitization is mediated by beta-arrestins, like most classic GPCRs. In
      contrast, internalization of PAR1 occurs through a clathrin- and dynamin
      dependent pathway independent of beta-arrestins. PAR1 displays two modes of
      internalization. Constitutive internalization of unactivated PAR1 is mediated by
      the clathrin adaptor protein complex-2 (AP-2), where the MU2-adaptin subunit
      binds directly to a tyrosine-based motif localized within the receptor C-tail
      domain. However, AP-2 depletion only partially inhibits agonist-induced
      internalization of PAR1, suggesting a function for other clathrin adaptors in
      this process. Here, we now report that AP-2 and epsin-1 are both critical
      mediators of agonist-stimulated PAR1 internalization. We show that ubiquitination
      of PAR1 and the ubiquitin-interacting motifs of epsin-1 are required for epsin-1
      dependent internalization of activated PAR1. In addition, activation of PAR1
      promotes epsin-1 de-ubiquitination, which may increase its endocytic adaptor
      activity to facilitate receptor internalization. AP-2 also regulates activated
      PAR1 internalization via recognition of distal C-tail phosphorylation sites
      rather than the canonical tyrosine-based motif. Thus, AP-2 and epsin-1 are both
      required to promote efficient internalization of activated PAR1 and recognize
      discrete receptor sorting signals. This study defines a new pathway for
      internalization of mammalian GPCRs.

PMID- 21965662
TI  - Qualitative and quantitative cellular glycomics of glycosphingolipids based on
      rhodococcal endoglycosylceramidase-assisted glycan cleavage, glycoblotting
      assisted sample preparation, and matrix-assisted laser desorption ionization
      tandem time-of-flight mass spectrometry analysis.
AB  - Glycosphingolipids (GSLs) are crucially important components of the cellular
      membrane, where they comprise microdomains with many critical biological
      functions. Despite this fact, qualitative and quantitative techniques for the
      analysis of GSLs still lag behind the needs of researchers. In this study, a
      reliable procedure for the elucidation of cellular GSL-glycomes was established
      based on (a) enzymatic glycan cleavage by endoglycosylceramidases derived from
      Rhodococcus sp. in combination with (b) glycoblotting-assisted sample
      preparation. The mixture of endoglycosylceramidase I and II was employed to
      maximize the release of glycan moieties from the major classes of GSLs (i.e.
      ganglio-, (neo)lacto- and globo-series GSLs). The glycoblotting technique enabled
      the quantitative detection of GSL-glycans using as few as 2 * 10(5) cells. Thirty
      seven different kinds of cellular GSL glycans were successfully observed in 11
      kinds of cells, including Chinese hamster ovary cells and their lectin-resistant
      mutants as well as murine and human embryonic carcinoma cells. Furthermore, in
      depth structural clarification in terms of discrimination of isomers was achieved
      by MALDI-TOF/TOF mass spectrometry analysis and/or linkage-specific glycosidase
      digestion. These novel analytical techniques were shown to be capable of
      delineating cell-specific GSL-glycomes. Thus, they are anticipated to have a
      broad range of applications for the characterization, description, and comparison
      of various cellular/tissue samples in the fields of drug discovery and
      regenerative medicine.

PMID- 21965664
TI  - hSWS1.SWSAP1 is an evolutionarily conserved complex required for efficient
      homologous recombination repair.
AB  - The Shu complex in yeast plays an important role in the homologous recombination
      pathway, which is critical for the maintenance of genomic integrity. The
      identification of human SWS1 (hSWS1) as the homolog of budding yeast Shu2
      implicated that the Shu complex is evolutionarily conserved. However, the human
      counterparts of other components in this complex have not yet been identified and
      characterized. Here we describe the characterization of a novel human component
      of this complex, SWSAP1 (hSWS1-associated protein 1)/C19orf39. We show that hSWS1
      and SWSAP1 form a stable complex in vivo and in vitro. hSWS1 and SWSAP1 are
      mutually interdependent for their stability. We further demonstrate that the
      purified hSWS1.SWSAP1 complex possesses single-stranded DNA-binding activity and
      DNA-stimulated ATPase activity. Moreover, SWSAP1 interacts with RAD51 and RAD51
      paralogs, and depletion of SWSAP1 causes defects in homologous recombination
      repair. Thus, our results suggest that the human Shu complex (hSWS1.SWSAP1) has
      an evolutionarily conserved function in homologous recombination.

PMID- 21965663
TI  - Regulation of RCAN1 protein activity by Dyrk1A protein-mediated phosphorylation.
AB  - Two genes on chromosome 21, namely dual specificity tyrosine phosphorylation
      regulated kinase 1A (Dyrk1A) and regulator of calcineurin 1 (RCAN1), have been
      implicated in some of the phenotypic characteristics of Down syndrome, including
      the early onset of Alzheimer disease. Although a link between Dyrk1A and RCAN1
      and the nuclear factor of activated T cells (NFAT) pathway has been reported, it
      remains unclear whether Dyrk1A directly interacts with RCAN1. In the present
      study, Dyrk1A is shown to directly interact with and phosphorylate RCAN1 at
      Ser(112) and Thr(192) residues. Dyrk1A-mediated phosphorylation of RCAN1 at
      Ser(112) primes the protein for the GSK3beta-mediated phosphorylation of
      Ser(108). Phosphorylation of RCAN1 at Thr(192) by Dyrk1A enhances the ability of
      RCAN1 to inhibit the phosphatase activity of calcineurin (Caln), leading to
      reduced NFAT transcriptional activity and enhanced Tau phosphorylation. These
      effects are mediated by the enhanced binding of RCAN1 to Caln and its extended
      half-life caused by Dyrk1A-mediated phosphorylation. Furthermore, an increased
      expression of phospho-Thr(192)-RCAN1 was observed in the brains of transgenic
      mice overexpressing the Dyrk1A protein. These results suggest a direct link
      between Dyrk1A and RCAN1 in the Caln-NFAT signaling and Tau hyperphosphorylation
      pathways, supporting the notion that the synergistic interaction between the
      chromosome 21 genes RCAN1 and Dyrk1A is associated with a variety of pathological
      features associated with DS.

PMID- 21965665
TI  - Interaction of beta2-glycoprotein I with lipopolysaccharide leads to Toll-like
      receptor 4 (TLR4)-dependent activation of macrophages.
AB  - beta(2)-Glycoprotein I (beta(2)GPI) is an abundant plasma protein that binds to
      the surface of cells and particles expressing negatively charged lipids, but its
      physiological role remains unknown. Antibodies to beta(2)GPI are found in
      patients with anti-phospholipid syndrome, a systemic autoimmune disease
      associated with vascular thrombosis and pregnancy morbidity. Although it has been
      suggested that anti-beta(2)GPI antibodies activate endothelial cells and
      monocytes by signaling through TLR4, it is unclear how anti-beta(2)GPI antibodies
      and/or beta(2)GPI interact with TLR4. A number of mammalian proteins (termed
      "endogenous Toll-like receptor (TLR) ligands") have been reported to bind to
      TLR4, but, in most cases, subsequent studies have shown that LPS interaction with
      these proteins is responsible for TLR activation. We hypothesized that, like
      other endogenous TLR ligands, beta(2)GPI interacts specifically with LPS and that
      this interaction is responsible for apparent TLR4 activation by beta(2)GPI. Here,
      we show that both LPS and TLR4 are required for beta(2)GPI to bind to and
      activate macrophages. Untreated beta(2)GPI stimulated TNF-alpha production in
      TLR4-sufficient (but not TLR4-deficient) macrophages. In contrast, neither
      polymyxin B-treated nor delipidated beta(2)GPI stimulated TNF-alpha production.
      Furthermore, beta(2)GPI bound to LPS in a specific and dose-dependent manner.
      Finally, untreated beta(2)GPI bound to the surface of TLR4-sufficient (but not
      TLR4-deficient) macrophages. Polymyxin B treatment of beta(2)GPI abolished
      macrophage binding. Our findings suggest a potential new biological activity for
      beta(2)GPI as a protein that interacts specifically with LPS and point to the
      need to evaluate newly discovered endogenous TLR ligands for potential
      interactions with LPS.

PMID- 21965667
TI  - Crystal structure of Fcgamma receptor I and its implication in high affinity
      gamma-immunoglobulin binding.
AB  - Fcgamma receptors (FcgammaRs) play critical roles in humoral and cellular immune
      responses through interactions with the Fc region of immunoglobulin G (IgG).
      Among them, FcgammaRI is the only high affinity receptor for IgG and thus is a
      potential target for immunotherapy. Here we report the first crystal structure of
      an FcgammaRI with all three extracellular Ig-like domains (designated as D1, D2,
      and D3). The structure shows that, first, FcgammaRI has an acute D1-D2 hinge
      angle similar to that of FcepsilonRI but much smaller than those observed in the
      low affinity Fcgamma receptors. Second, the D3 domain of FcgammaRI is positioned
      away from the putative IgG binding site on the receptor and is thus unlikely to
      make direct contacts with Fc. Third, the replacement of FcgammaRIII FG-loop
      ((171)LVGSKNV(177)) with that of FcgammaRI ((171)MGKHRY(176)) resulted in a 15
      fold increase in IgG(1) binding affinity, whereas a valine insertion in the
      FcgammaRI FG-loop ((171)MVGKHRY(177)) abolished the affinity enhancement. Thus,
      the FcgammaRI FG-loop with its conserved one-residue deletion is critical to the
      high affinity IgG binding. The structural results support FcgammaRI binding to
      IgG in a similar mode as its low affinity counterparts. Taken together, our study
      suggests a molecular mechanism for the high affinity IgG recognition by FcgammaRI
      and provides a structural basis for understanding its physiological function and
      its therapeutic implication in treating autoimmune diseases.

PMID- 21965666
TI  - Pyroglutamate amyloid-beta (Abeta): a hatchet man in Alzheimer disease.
AB  - Pyroglutamate-modified amyloid-beta (Abeta(pE3)) peptides are gaining
      considerable attention as potential key participants in the pathology of
      Alzheimer disease (AD) due to their abundance in AD brain, high aggregation
      propensity, stability, and cellular toxicity. Transgenic mice that produce high
      levels of Abeta(pE3-42) show severe neuron loss. Recent in vitro and in vivo
      experiments have proven that the enzyme glutaminyl cyclase catalyzes the
      formation of Abeta(pE3). In this minireview, we summarize the current knowledge
      on Abeta(pE3), discussing its discovery, biochemical properties, molecular events
      determining formation, prevalence in the brains of AD patients, Alzheimer mouse
      models, and potential as a target for therapy and as a diagnostic marker.

PMID- 21965668
TI  - Relationship of axonal voltage-gated sodium channel 1.8 (NaV1.8) mRNA
      accumulation to sciatic nerve injury-induced painful neuropathy in rats.
AB  - Painful peripheral neuropathy is a significant clinical problem; however, its
      pathological mechanism and effective treatments remain elusive. Increased
      peripheral expression of tetrodotoxin-resistant voltage-gated sodium channel 1.8
      (NaV1.8) has been shown to associate with chronic pain symptoms in humans and
      experimental animals. Sciatic nerve entrapment (SNE) injury was used to develop
      neuropathic pain symptoms in rats, resulting in increased NaV1.8 mRNA in the
      injured nerve but not in dorsal root ganglia (DRG). To study the role of NaV1.8
      mRNA in the pathogenesis of SNE-induced painful neuropathy, NaV1.8 shRNA vector
      was delivered by subcutaneous injection of cationized gelatin/plasmid DNA
      polyplex into the rat hindpaw and its subsequent retrograde transport via sciatic
      nerve to DRG. This in vivo NaV1.8 shRNA treatment reversibly and repeatedly
      attenuated the SNE-induced pain symptoms, an effect that became apparent
      following a distinct lag period of 3-4 days and lasted for 4-6 days before
      returning to pretreatment levels. Surprisingly, apparent knockdown of NaV1.8 mRNA
      occurred only in the injured nerve, not in the DRG, during the pain alleviation
      period. Levels of heteronuclear NaV1.8 RNA were unaffected by SNE or shRNA
      treatments, suggesting that transcription of the Scn10a gene encoding NaV1.8 was
      unchanged. Based on these data, we postulate that increased axonal mRNA transport
      results in accumulation of functional NaV1.8 protein in the injured nerve and the
      development of painful neuropathy symptoms. Thus, targeted delivery of agents
      that interfere with axonal NaV1.8 mRNA may represent effective neuropathic pain
      treatments.

PMID- 21965669
TI  - Thermally unstable gating of the most common cystic fibrosis mutant channel
      (DeltaF508): "rescue" by suppressor mutations in nucleotide binding domain 1 and
      by constitutive mutations in the cytosolic loops.
AB  - Most cystic fibrosis (CF) cases are caused by the DeltaF508 mutation in the CF
      transmembrane conductance regulator (CFTR), which disrupts both the processing
      and gating of this chloride channel. The cell surface expression of DeltaF508
      CFTR can be "rescued" by culturing cells at 26-28  degrees C and treating cells
      with small molecule correctors or intragenic suppressor mutations. Here, we
      determined whether these various rescue protocols induce a DeltaF508-CFTR
      conformation that is thermally stable in excised membrane patches. We also tested
      the impact of constitutive cytosolic loop mutations that increase ATP-independent
      channel activity (K978C and K190C/K978C) on DeltaF508-CFTR function. Low
      temperature-rescued DeltaF508-CFTR channels irreversibly inactivated with a time
      constant of 5-6 min when excised patches were warmed from 22  degrees C to 36.5 
      degrees C. A panel of CFTR correctors and potentiators that increased DeltaF508
      CFTR maturation or channel activity failed to prevent this inactivation.
      Conversely, three suppressor mutations in the first nucleotide binding domain
      rescued DeltaF508-CFTR maturation and stabilized channel activity at 36.5 
      degrees C. The constitutive loop mutations increased ATP-independent activity of
      low temperature-rescued DeltaF508-CFTR but did not enhance protein maturation.
      Importantly, the ATP-independent activities of these DeltaF508-CFTR constructs
      were stable at 36.5  degrees C, whereas their ATP-dependent activities were not.
      Single channel recordings of this thermally stable ATP-independent activity
      revealed dynamic gating and unitary currents of normal amplitudes. We conclude
      that: (i) DeltaF508-CFTR gating is highly unstable at physiologic temperature;
      (ii) most rescue protocols do not prevent this thermal instability; and (iii) ATP
      independent gating and the pore are spared from DeltaF508-induced thermal
      instability, a finding that may inform alternative treatment strategies.

PMID- 21965670
TI  - The C-terminal alphaI domain linker as a critical structural element in the
      conformational activation of alphaI integrins.
AB  - The activation of alpha/beta heterodimeric integrins is the result of highly
      coordinated rearrangements within both subunits. The molecular interactions
      between the two subunits, however, remain to be characterized. In this study, we
      use the integrin alpha(L)beta(2) to investigate the functional role of the C
      linker polypeptide that connects the C-terminal end of the inserted (I) domain
      with the beta-propeller domain on the alpha subunit and is located at the
      interface with the betaI domain of the beta chain. We demonstrate that shortening
      of the C-linker by eight or more amino acids results in constitutively active
      alpha(L)beta(2) in which the alphaI domain is no longer responsive to the
      regulation by the betaI domain. Despite this intersubunit uncoupling, both I
      domains remain individually sensitive to intrasubunit conformational changes
      induced by allosteric modulators. Interestingly, the length and not the sequence
      of the C-linker appears to be critical for its functionality in alpha/beta
      intersubunit communication. Using two monoclonal antibodies (R7.1 and CBR LFA
      1/1) we further demonstrate that shortening of the C-linker results in the
      gradual loss of combinational epitopes that require both the alphaI and beta
      propeller domains for full reactivity. Taken together, our findings highlight the
      role of the C-linker as a spring-like element that allows relaxation of the
      alphaI domain in the resting state and controlled tension of the alphaI domain
      during activation, exerted by the beta chain.

PMID- 21965671
TI  - Molecular convergence of bacterial and eukaryotic surface order.
AB  - The conservation of fluidity is a theme common to all cell membranes. In this
      study, an analysis of lipid packing was conducted via C-laurdan spectroscopy of
      cell surface membranes prepared from representative species of Bacteria and
      Eukarya. We found that despite their radical differences in composition (namely
      the presence and absence of membrane-rigidifying sterol) the membrane order of
      all taxa converges on a remarkably similar level. To understand how this
      similarity is constructed, we reconstituted membranes with either bacterial or
      eukaryotic components. We found that transmembrane segments of proteins have an
      important role in buffering lipid-mediated packing. This buffering ensures that
      sterol-free and sterol-containing membranes exhibit similar barrier properties.

PMID- 21965672
TI  - Multiple functions of aromatic-carbohydrate interactions in a processive
      cellulase examined with molecular simulation.
AB  - Proteins employ aromatic residues for carbohydrate binding in a wide range of
      biological functions. Glycoside hydrolases, which are ubiquitous in nature,
      typically exhibit tunnels, clefts, or pockets lined with aromatic residues for
      processing carbohydrates. Mutation of these aromatic residues often results in
      significant activity differences on insoluble and soluble substrates. However,
      the thermodynamic basis and molecular level role of these aromatic residues
      remain unknown. Here, we calculate the relative ligand binding free energy by
      mutating tryptophans in the Trichoderma reesei family 6 cellulase (Cel6A) to
      alanine. Removal of aromatic residues near the catalytic site has little impact
      on the ligand binding free energy, suggesting that aromatic residues immediately
      upstream of the active site are not directly involved in binding, but play a role
      in the glucopyranose ring distortion necessary for catalysis. Removal of aromatic
      residues at the entrance and exit of the Cel6A tunnel, however, dramatically
      impacts the binding affinity, suggesting that these residues play a role in chain
      acquisition and product stabilization, respectively. The roles suggested from
      differences in binding affinity are confirmed by molecular dynamics and normal
      mode analysis. Surprisingly, our results illustrate that aromatic-carbohydrate
      interactions vary dramatically depending on the position in the enzyme tunnel. As
      aromatic-carbohydrate interactions are present in all carbohydrate-active
      enzymes, these results have implications for understanding protein structure
      function relationships in carbohydrate metabolism and recognition, carbon
      turnover in nature, and protein engineering strategies for biomass utilization.
      Generally, these results suggest that nature employs aromatic-carbohydrate
      interactions with a wide range of binding affinities for diverse functions.

PMID- 21965673
TI  - N-acetylglucosamine inhibits T-helper 1 (Th1)/T-helper 17 (Th17) cell responses
      and treats experimental autoimmune encephalomyelitis.
AB  - Current treatments and emerging oral therapies for multiple sclerosis (MS) are
      limited by effectiveness, cost, and/or toxicity. Genetic and environmental
      factors that alter the branching of Asn (N)-linked glycans result in T cell
      hyperactivity, promote spontaneous inflammatory demyelination and
      neurodegeneration in mice, and converge to regulate the risk of MS. The sugar N
      acetylglucosamine (GlcNAc) enhances N-glycan branching and inhibits T cell
      activity and adoptive transfer experimental autoimmune encephalomyelitis (EAE).
      Here, we report that oral GlcNAc inhibits T-helper 1 (Th1) and T-helper 17 (Th17)
      responses and attenuates the clinical severity of myelin oligodendrocyte
      glycoprotein (MOG)-induced EAE when administered after disease onset. Oral GlcNAc
      increased expression of branched N-glycans in T cells in vivo as shown by high pH
      anion exchange chromatography, MALDI-TOF mass spectroscopy and FACS analysis with
      the plant lectin l-phytohemagglutinin. Initiating oral GlcNAc treatment on the
      second day of clinical disease inhibited MOG-induced EAE as well as secretion of
      interferon-gamma, tumor necrosis factor-alpha, interleukin-17, and interleukin
      22. In the more severe 2D2 T cell receptor transgenic EAE model, oral GlcNAc
      initiated after disease onset also inhibits clinical disease, except for those
      with rapid lethal progression. These data suggest that oral GlcNAc may provide an
      inexpensive and nontoxic oral therapeutic agent for MS that directly targets an
      underlying molecular mechanism causal of disease.

PMID- 21965674
TI  - Special AT-rich binding protein-2 (SATB2) differentially affects disease-causing
      p63 mutant proteins.
AB  - p63, a p53 family member, is critical for proper skin and limb development and
      directly regulates gene expression in the ectoderm. Mice lacking p63 exhibit skin
      and craniofacial defects including cleft palate. In humans p63 mutations are
      associated with several distinct developmental syndromes. p63 sterile-alpha-motif
      domain, AEC (ankyloblepharon-ectodermal dysplasia-clefting)-associated mutations
      are associated with a high prevalence of orofacial clefting disorders, which are
      less common in EEC (ectrodactyly-ectodermal dysplasia-clefting) patients with DNA
      binding domain p63 mutations. However, the mechanisms by which these mutations
      differentially influence p63 function remain unclear, and interactions with other
      proteins implicated in craniofacial development have not been identified. Here,
      we show that AEC p63 mutations affect the ability of the p63 protein to interact
      with special AT-rich binding protein-2 (SATB2), which has recently also been
      implicated in the development of cleft palate. p63 and SATB2 are co-expressed
      early in development in the ectoderm of the first and second branchial arches,
      two essential sites where signaling is required for craniofacial patterning.
      SATB2 attenuates p63-mediated gene expression of perp (p53 apoptosis effector
      related to PMP-22), a critical downstream target gene during development, and
      specifically decreases p63 perp promoter binding. Interestingly, AEC but not EEC
      p63 mutations affect the ability of p63 to interact with SATB2 and the inhibitory
      effects of SATB2 on p63 transactivation of perp are most pronounced for AEC
      associated p63 mutations. Our findings reveal a novel gain-of-function property
      of AEC-causing p63 mutations and identify SATB2 as the first p63 binding partner
      that differentially influences AEC and EEC p63 mutant proteins.

PMID- 21965675
TI  - Members of the salivary gland surface protein (SGS) family are major immunogenic
      components of mosquito saliva.
AB  - Mosquitoes transmit Plasmodium and certain arboviruses during blood feeding, when
      they are injected along with saliva. Mosquito saliva interferes with the host's
      hemostasis and inflammation response and influences the transmission success of
      some pathogens. One family of mosquito salivary gland proteins, named SGS, is
      composed of large bacterial-type proteins that in Aedes aegypti were implicated
      as receptors for Plasmodium on the basal salivary gland surface. Here, we
      characterize the biology of two SGSs in the malaria mosquito, Anopheles gambiae,
      and demonstrate their involvement in blood feeding. Western blots and RT-PCR
      showed that Sgs4 and Sgs5 are produced exclusively in female salivary glands,
      that expression increases with age and after blood feeding, and that protein
      levels fluctuate in a circadian manner. Immunohistochemistry showed that SGSs are
      present in the acinar cells of the distal lateral lobes and in the salivary ducts
      of the proximal lobes. SDS-PAGE, Western blots, bite blots, and immunization via
      mosquito bites showed that SGSs are highly immunogenic and form major components
      of mosquito saliva. Last, Western and bioinformatic analyses suggest that SGSs
      are secreted via a non-classical pathway that involves cleavage into a 300-kDa
      soluble fragment and a smaller membrane-bound fragment. Combined, these data
      strongly suggest that SGSs play an important role in blood feeding. Together with
      their role in malaria transmission, we propose that SGSs could be used as markers
      of human exposure to mosquito bites and in the development of disease control
      strategies.

PMID- 21965676
TI  - Reciprocal regulation between proinflammatory cytokine-induced inducible NO
      synthase (iNOS) and connexin43 in bladder smooth muscle cells.
AB  - Gap junctions (GJs) play an important role in the control of bladder contractile
      response and in the regulation of various immune inflammatory processes. Here, we
      investigated the possible interaction between inflammation and GJs in bladder
      smooth muscle cells (BSMCs). Stimulation of BSMCs with IL1beta and TNFalpha
      increased connexin43 (Cx43) expression and function, which was associated with
      increased phosphorylation of vasodilator-stimulated phosphoprotein. Inhibition of
      PKA with H89 or down-regulation of CREB with specific siRNAs largely abolished
      the Cx43-elevating effect. Further analysis revealed that IL1beta/TNFalpha
      induced NFkappaB-dependent inducible NO synthase (iNOS) expression. Inhibition of
      iNOS with G-nitro-l-arginine methyl ester abrogated and an exogenous NO donor
      mimicked the effect of the cytokines on Cx43. Intraperitoneal injection of LPS
      into mice also induced bladder Cx43 expression, which was largely blocked by an
      iNOS inhibitor. Finally, the elevated Cx43 was found to negatively regulate iNOS
      expression. Dysfunction of GJs with various blockers or down-regulation of Cx43
      with siRNA significantly potentiated the expression of iNOS. Fibroblasts from
      Cx43 knock-out (Cx43(-/-)) mice also displayed a significantly higher response to
      the cytokine-induced iNOS expression than cells from Cx43 wild-type (Cx43(+/+))
      littermates. Collectively, our study revealed a previously unrecognized
      reciprocal regulation loop between cytokine-induced NO and GJs. Our findings may
      provide an important molecular mechanism for the symptoms of bladder infection.
      In addition, it may further our understanding of the roles of GJs in inflammatory
      diseases.

PMID- 21965677
TI  - Novel p65 binding glucocorticoid-induced leucine zipper peptide suppresses
      experimental autoimmune encephalomyelitis.
AB  - Multiple sclerosis (MS) is a neurological disease characterized by inflammatory
      demyelination in the brain and spinal cord. The immune-mediated inflammation
      involves well orchestrated intermolecular interactions that exhibit rapid binding
      kinetics. The binding interfaces of transient interactions frequently include
      proline residues that favor an extended conformation for molecular recognition.
      Linear interface peptides are excellent lead inhibitors of specific protein
      protein interactions because only small segments of the interface contribute to
      the binding. Glucocorticoid-induced leucine zipper (GILZ), a recently identified
      molecule exhibits potent anti-inflammatory properties. Mechanistically, a proline
      rich segment in the carboxyl terminus of GILZ physically binds the p65 subunit of
      nuclear factor-kappaB and inhibits the transactivation of inflammatory cytokines.
      Integrating knowledge derived from the mechanism of action of GILZ with in silico
      structure prediction identified an immunomodulatory peptide, the GILZ-P.
      Treatment with GILZ-P exhibited therapeutic efficacy in experimental autoimmune
      encephalomyelitis, a model for human MS.

PMID- 21965678
TI  - SUMOylation and SUMO-interacting motif (SIM) of metastasis tumor antigen 1 (MTA1)
      synergistically regulate its transcriptional repressor function.
AB  - Metastasis tumor antigen 1 (MTA1), a component of the Mi-2.nucleosome remodeling
      and deacetylase complex, plays a crucial role in gene transcription, but the
      mechanism involved remains largely unknown. Here, we report that MTA1 is a
      substrate for small ubiquitin-related modifier 2/3 (SUMO2/3) in vivo. Protein
      inhibitor of activated STAT (PIAS) proteins enhance SUMOylation of MTA1 and may
      participate in paralog-selective SUMOylation, whereas sentrin/SUMO-specific
      protease 1 (SENP1) and 2 may act as deSUMOylation enzymes for MTA1. Moreover,
      MTA1 contains a functional SUMO-interacting motif (SIM) at its C terminus, and
      SIM is required for the efficient SUMOylation of MTA1. SUMO conjugation on Lys
      509, which is located within the SUMO consensus site, together with SIM
      synergistically regulates the co-repressor activity of MTA1 on PS2 transcription,
      probably by recruiting HDAC2 onto the PS2 promoter. Interestingly, MTA1 may up
      regulate the expression of SUMO2 via interaction with RNA polymerase II and SP1
      at the SUMO2 promoter. These findings not only provide novel mechanistic insights
      into the regulation of the transcriptional repressor function of MTA1 by
      SUMOylation and SIM but also uncover a potential function of MTA1 in modulating
      the SUMOylation pathway.

PMID- 21965679
TI  - Interleukin-36 (IL-36) ligands require processing for full agonist (IL-36alpha,
      IL-36beta, and IL-36gamma) or antagonist (IL-36Ra) activity.
AB  - IL-36alpha, IL-36beta, and IL-36gamma (formerly IL-1F6, IL-1F8, and IL-1F9) are
      IL-1 family members that signal through the IL-1 receptor family members IL-1Rrp2
      (IL-1RL2) and IL-1RAcP. IL-36Ra (formerly IL-1F5) has been reported to antagonize
      IL-36gamma. However, our previous attempts to demonstrate IL-36Ra antagonism were
      unsuccessful. Here, we demonstrate that IL-36Ra antagonist activity is dependent
      upon removal of its N-terminal methionine. IL-36Ra starting at Val-2 is fully
      active and capable of inhibiting not only IL-36gamma but also IL-36alpha and IL
      36beta. Val-2 of IL-36Ra lies 9 amino acids N-terminal to an A-X-Asp motif
      conserved in all IL-1 family members. In further experiments, we show that
      truncation of IL-36alpha, IL-36beta, and IL-36gamma to this same point increased
      their specific activity by ~10(3)-10(4)-fold (from EC(50) 1 MUg/ml to EC(50) 1
      ng/ml). Inhibition of truncated IL-36beta activity required ~10(2)-10(3)-fold
      excess IL-36Ra, similar to the ratio required for IL-1Ra to inhibit IL-1beta.
      Chimeric receptor experiments demonstrated that the extracellular (but not
      cytoplasmic) domain of IL-1Rrp2 or IL-1R1 is required for inhibition by their
      respective natural antagonists. IL-36Ra bound to IL-1Rrp2, and pretreatment of IL
      1Rrp2-expressing cells with IL-36Ra prevented IL-36beta-mediated co
      immunoprecipitation of IL-1Rrp2 with IL-1RAcP. Taken together, these results
      suggest that the mechanism of IL-36Ra antagonism is analogous to that of IL-1Ra,
      such that IL-36Ra binds to IL-1Rrp2 and prevents IL-1RAcP recruitment and the
      formation of a functional signaling complex. In addition, truncation of IL
      36alpha, IL-36beta, and IL-36gamma dramatically enhances their activity,
      suggesting that post-translational processing is required for full activity.

PMID- 21965680
TI  - Structural and biochemical characterization of the salicylyl-acyltranferase SsfX3
      from a tetracycline biosynthetic pathway.
AB  - SsfX3 is a GDSL family acyltransferase that transfers salicylate to the C-4
      hydroxyl of a tetracycline intermediate in the penultimate step during
      biosynthesis of the anticancer natural product SF2575. The C-4 salicylate takes
      the place of the more common C-4 dimethylamine functionality, making SsfX3 the
      first acyltransferase identified to act on a tetracycline substrate. The crystal
      structure of SsfX3 was determined at 2.5 A, revealing two distinct domains as
      follows: an N-terminal beta-sandwich domain that resembles a carbohydrate-binding
      module, and a C-terminal catalytic domain that contains the atypical alpha/beta
      hydrolase fold found in the GDSL hydrolase family of enzymes. The active site
      lies at one end of a large open binding pocket, which is spatially defined by
      structural elements from both the N- and C-terminal domains. Mutational analysis
      in the putative substrate binding pocket identified residues from both domains
      that are important for binding the acyl donor and acceptor. Furthermore, removal
      of the N-terminal carbohydrate-binding module-like domain rendered the stand
      alone alpha/beta-hydrolase domain inactive. The additional noncatalytic module is
      therefore proposed to be required to define the binding pocket and provide
      sufficient interactions with the spatially extended tetracyclic substrate. SsfX3
      was also demonstrated to accept a variety of non-native acyl groups. This relaxed
      substrate specificity toward the acyl donor allowed the chemoenzymatic
      biosynthesis of C-4-modified analogs of the immediate precursor to the bioactive
      SF2575; these were used to assay the structure activity relationships at the C-4
      position.

PMID- 21965681
TI  - Plasma membrane calcium pump (PMCA4)-neuronal nitric-oxide synthase complex
      regulates cardiac contractility through modulation of a compartmentalized cyclic
      nucleotide microdomain.
AB  - Identification of the signaling pathways that regulate cyclic nucleotide
      microdomains is essential to our understanding of cardiac physiology and
      pathophysiology. Although there is growing evidence that the plasma membrane
      Ca(2+)/calmodulin-dependent ATPase 4 (PMCA4) is a regulator of neuronal nitric
      oxide synthase, the physiological consequence of this regulation is unclear. We
      therefore tested the hypothesis that PMCA4 has a key structural role in tethering
      neuronal nitric-oxide synthase to a highly compartmentalized domain in the
      cardiac cell membrane. This structural role has functional consequences on cAMP
      and cGMP signaling in a PMCA4-governed microdomain, which ultimately regulates
      cardiac contractility. In vivo contractility and calcium amplitude were increased
      in PMCA4 knock-out animals (PMCA4(-/-)) with no change in diastolic relaxation or
      the rate of calcium decay, showing that PMCA4 has a function distinct from beat
      to-beat calcium transport. Surprisingly, in PMCA4(-/-), over 36% of membrane
      associated neuronal nitric-oxide synthase (nNOS) protein and activity was
      delocalized to the cytosol with no change in total nNOS protein, resulting in a
      significant decrease in microdomain cGMP, which in turn led to a significant
      elevation in local cAMP levels through a decrease in PDE2 activity (measured by
      FRET-based sensors). This resulted in increased L-type calcium channel activity
      and ryanodine receptor phosphorylation and hence increased contractility. In the
      heart, in addition to subsarcolemmal calcium transport, PMCA4 acts as a
      structural molecule that maintains the spatial and functional integrity of the
      nNOS signaling complex in a defined microdomain. This has profound consequences
      for the regulation of local cyclic nucleotide and hence cardiac beta-adrenergic
      signaling.

PMID- 21965682
TI  - Structure and function of papiliocin with antimicrobial and anti-inflammatory
      activities isolated from the swallowtail butterfly, Papilio xuthus.
AB  - Papiliocin is a novel 37-residue cecropin-like peptide isolated recently from the
      swallowtail butterfly, Papilio xuthus. With the aim of identifying a potent
      antimicrobial peptide, we tested papiliocin in a variety of biological and
      biophysical assays, demonstrating that the peptide possesses very low
      cytotoxicity against mammalian cells and high bacterial cell selectivity,
      particularly against Gram-negative bacteria as well as high anti-inflammatory
      activity. Using LPS-stimulated macrophage RAW264.7 cells, we found that
      papiliocin exerted its anti-inflammatory activities by inhibiting nitric oxide
      (NO) production and secretion of tumor necrosis factor (TNF)-alpha and macrophage
      inflammatory protein (MIP)-2, producing effects comparable with those of the
      antimicrobial peptide LL-37. We also showed that the innate defense response
      mechanisms engaged by papiliocin involve Toll-like receptor pathways that
      culminate in the nuclear translocation of NF-kappaB. Fluorescent dye leakage
      experiments showed that papiliocin targets the bacterial cell membrane. To
      understand structure-activity relationships, we determined the three-dimensional
      structure of papiliocin in 300 mm dodecylphosphocholine micelles by NMR
      spectroscopy, showing that papiliocin has an alpha-helical structure from Lys(3)
      to Lys(21) and from Ala(25) to Val(36), linked by a hinge region. Interactions
      between the papiliocin and LPS studied using tryptophan blue-shift data, and
      saturation transfer difference-NMR experiments revealed that Trp(2) and Phe(5) at
      the N-terminal helix play an important role in attracting papiliocin to the cell
      membrane of Gram-negative bacteria. In conclusion, we have demonstrated that
      papiliocin is a potent peptide antibiotic with both anti-inflammatory and
      antibacterial activities, and we have laid the groundwork for future studies of
      its mechanism of action.

PMID- 21965683
TI  - 14-3-3 binding and phosphorylation of neuroglobin during hypoxia modulate six-to
      five heme pocket coordination and rate of nitrite reduction to nitric oxide.
AB  - Neuroglobin protects neurons from hypoxia in vitro and in vivo; however, the
      underlying mechanisms for this effect remain poorly understood. Most of the
      neuroglobin is present in a hexacoordinate state with proximal and distal
      histidines in the heme pocket directly bound to the heme iron. At equilibrium,
      the concentration of the five-coordinate neuroglobin remains very low (0.1-5%).
      Recent studies have shown that post-translational redox regulation of neuroglobin
      surface thiol disulfide formation increases the open probability of the heme
      pocket and allows nitrite binding and reaction to form NO. We hypothesized that
      the equilibrium between the six- and five-coordinate states and secondary
      reactions with nitrite to form NO could be regulated by other hypoxia-dependent
      post-translational modification(s). Protein sequence models identified candidate
      sites for both 14-3-3 binding and phosphorylation. In both in vitro experiments
      and human SH-SY5Y neuronal cells exposed to hypoxia and glucose deprivation, we
      observed that 1) neuroglobin phosphorylation and protein-protein interactions
      with 14-3-3 increase during hypoxic and metabolic stress; 2) neuroglobin binding
      to 14-3-3 stabilizes and increases the half-life of phosphorylation; and 3)
      phosphorylation increases the open probability of the heme pocket, which
      increases ligand binding (CO and nitrite) and accelerates the rate of anaerobic
      nitrite reduction to form NO. These data reveal a series of hypoxia-dependent
      post-translational modifications to neuroglobin that regulate the six-to-five
      heme pocket equilibrium and heme access to ligands. Hypoxia-regulated reactions
      of nitrite and neuroglobin may contribute to the cellular adaptation to hypoxia.

PMID- 21965684
TI  - The structure of the PDZ3-SH3-GuK tandem of ZO-1 protein suggests a supramodular
      organization of the membrane-associated guanylate kinase (MAGUK) family scaffold
      protein core.
AB  - Membrane-associated guanylate kinases (MAGUKs) are a large family of scaffold
      proteins that play essential roles in tethering membrane receptors, adhesion
      molecules, and macromolecular signaling complexes for tissue developments, cell
      cell communications, and intracellular signal transductions. The defining feature
      of the MAGUK family scaffolds is that each member contains a conserved core
      consisting of a PSD-95/Dlg/ZO-1 (PDZ) domain, an Src homology 3 (SH3) domain, and
      a catalytically inactive guanylate kinase (GuK) domain arranged in tandem,
      although the structural features and functional implications of the PDZ-SH3-GuK
      tandem arrangement are unclear. The structure of the ZO-1 PDZ3-SH3-GuK tandem
      solved in this study reveals that the PDZ domain directly interacts with the SH3
      GuK module, forming a structural supramodule with distinct target binding
      properties with respect to the isolated domains. Structure-based sequence
      analysis suggests that the PDZ-SH3-GuK tandems of other members of the MAGUK
      family also form supramodules.

PMID- 21965685
TI  - External Ba2+ block of the two-pore domain potassium channel TREK-1 defines
      conformational transition in its selectivity filter.
AB  - TREK-1 is a member of the two-pore domain potassium channel family that is known
      as a leak channel and plays a key role in many physiological and pathological
      processes. The conformational transition of the selectivity filter is considered
      as an effective strategy for potassium channels to control the course of
      potassium efflux. It is well known that TREK-1 is regulated by a large volume of
      extracellular and intracellular signals. However, until now, little was known
      about the selectivity filter gating mechanism of the channel. In this research,
      it was found that Ba(2+) blocked the TREK-1 channel in a concentration- and time
      dependent manner. A mutagenesis analysis showed that overlapped binding of Ba(2+)
      at the assumed K(+) binding site 4 (S4) within the selectivity filter was
      responsible for the inhibitory effects on TREK-1. Then, Ba(2+) was used as a
      probe to explore the conformational transition in the selectivity filter of the
      channel. It was confirmed that collapsed conformations were induced by
      extracellular K(+)-free and acidification at the selectivity filters, leading to
      nonconductive to permeable ions. Further detailed characterization demonstrated
      that the two conformations presented different properties. Additionally, the N
      terminal truncated isoform (DeltaN41), a product derived from alternative
      translation initiation, was identified as a constitutively nonconductive variant.
      Together, these results illustrate the important role of selectivity filter
      gating in the regulation of TREK-1 by the extracellular K(+) and proton.

PMID- 21965686
TI  - Molecular determinants of CaV2.1 channel regulation by calcium-binding protein-1.
AB  - Presynaptic Ca(V)2.1 channels, which conduct P/Q-type Ca(2+) currents, initiate
      synaptic transmission at most synapses in the central nervous system. Regulation
      of Ca(V)2.1 channels by CaM contributes significantly to short term facilitation
      and rapid depression of synaptic transmission. Short term synaptic plasticity is
      diverse in form and function at different synapses, yet CaM is ubiquitously
      expressed. Differential regulation of Ca(V)2.1 channels by CaM-like Ca(2+) sensor
      (CaS) proteins differentially affects short term synaptic facilitation and rapid
      synaptic depression in transfected sympathetic neuron synapses. Here, we define
      the molecular determinants for differential regulation of Ca(V)2.1 channels by
      the CaS protein calcium-binding protein-1 (CaBP1) by analysis of chimeras in
      which the unique structural domains of CaBP1 are inserted into CaM. Our results
      show that the N-terminal domain, including its myristoylation site, and the
      second EF-hand, which is inactive in Ca(2+) binding, are the key molecular
      determinants of differential regulation of Ca(V)2.1 channels by CaBP1. These
      findings give insight into the molecular code by which CaS proteins
      differentially regulate Ca(V)2.1 channel function and provide diversity of form
      and function of short term synaptic plasticity.

PMID- 21965687
TI  - The transition from closed to open conformation of Treponema pallidum outer
      membrane-associated lipoprotein TP0453 involves membrane sensing and integration
      by two amphipathic helices.
AB  - The molecular architecture and composition of the outer membrane (OM) of
      Treponema pallidum (Tp), the noncultivable agent of venereal syphilis, differ
      considerably from those of typical Gram-negative bacteria. Several years ago we
      described TP0453, the only lipoprotein associated with the inner leaflet of the
      Tp OM. Whereas polypeptides of other treponemal lipoproteins are hydrophilic, non
      lipidated TP0453 can integrate into membranes, a property attributed to its
      multiple amphipathic helices (AHs). Furthermore, membrane integration of the
      TP0453 polypeptide was found to increase membrane permeability, suggesting the
      molecule functions in a porin-like manner. To better understand the mechanism of
      membrane integration of TP0453 and its physiological role in Tp OM biogenesis, we
      solved its crystal structure and used mutagenesis to identify membrane insertion
      elements. The crystal structure of TP0453 consists of an alpha/beta/alpha-fold
      and includes five stably folded AHs. In high concentrations of detergent, TP0453
      transitions from a closed to open conformation by lateral movement of two groups
      of AHs, exposing a large hydrophobic cavity. Triton X-114 phase partitioning,
      liposome floatation assay, and bis-1-anilino-8-naphthalenesulfonate binding
      revealed that two adjacent AHs are critical for membrane sensing/integration.
      Using terbium-dipicolinic acid complex-loaded large unilamellar vesicles, we
      found that TP0453 increased efflux of fluorophore only at acidic pH. Gel
      filtration and cross-linking experiments demonstrated that one AH critical for
      membrane sensing/insertion also forms a dimeric interface. Based on structural
      dynamics and comparison with Mycobacterium tuberculosis lipoproteins LprG and
      LppX, we propose that TP0453 functions as a carrier of lipids, glycolipids,
      and/or derivatives during OM biogenesis.

PMID- 21965690
TI  - Time for change in the conduct of clinical trials in patients with rheumatoid
      arthritis.

PMID- 21965691
TI  - The Wisdom of the PHAROS.

PMID- 21965688
TI  - Structure of the C-terminal domain of Neisseria heparin binding antigen (NHBA),
      one of the main antigens of a novel vaccine against Neisseria meningitidis.
AB  - Neisseria heparin binding antigen (NHBA), also known as GNA2132 (genome-derived
      Neisseria antigen 2132), is a surface-exposed lipoprotein from Neisseria
      meningitidis that was originally identified by reverse vaccinology. It is one the
      three main antigens of a multicomponent vaccine against serogroup B meningitis
      (4CMenB), which has just completed phase III clinical trials in infants. In
      contrast to the other two main vaccine components, little is known about the
      origin of the immunogenicity of this antigen, and about its ability to induce a
      strong cross-bactericidal response in animals and humans. To characterize NHBA in
      terms of its structural/immunogenic properties, we have analyzed its sequence and
      identified a C-terminal region that is highly conserved in all strains. We
      demonstrate experimentally that this region is independently folded, and solved
      its three-dimensional structure by nuclear magnetic resonance. Notably, we need
      detergents to observe a single species in solution. The NHBA domain fold consists
      of an 8-strand beta-barrel that closely resembles the C-terminal domains of N.
      meningitidis factor H-binding protein and transferrin-binding protein B. This
      common fold together with more subtle structural similarities suggest a common
      ancestor for these important antigens and a role of the beta-barrel fold in
      inducing immunogenicity against N. meningitidis. Our data represent the first
      step toward understanding the relationship between structural, functional, and
      immunological properties of this important vaccine component.

PMID- 21965692
TI  - An added perspective on the 2009 SPARTAN and IGAS report: an innate axial
      myofascial hypertonicity.

PMID- 21965693
TI  - Lumbar radiculopathy due to gas-containing pseudocyst.

PMID- 21965694
TI  - Pseudotumor from a metal-on-metal hip.

PMID- 21965695
TI  - Rehabilitation treatment strategies in ankylosing spondylitis.

PMID- 21965696
TI  - Desensitization to hydroxychloroquine: 4 cases.

PMID- 21965697
TI  - Subglottic stenosis is a form of limited Wegener's granulomatosis.

PMID- 21965698
TI  - Disease-related risk of vertebral fracture during glucocorticoid treatment of
      collagen vascular diseases.

PMID- 21965699
TI  - Temporomandibular joint arthritis in pediatric sjogren disease and sarcoidosis.

PMID- 21965700
TI  - Fecal calprotectin in children with the enthesitis-related arthritis subtype of
      juvenile idiopathic arthritis.

PMID- 21965701
TI  - Enhancement of the affinity of glucocorticoid receptors as a mechanism underlying
      the steroid-sparing effect of intravenous immunoglobulin.

PMID- 21965702
TI  - Hyperimmunoglobulinemia d syndrome variant--seek and you shall find.

PMID- 21965703
TI  - Hydrocephalus in Wegener's granulomatosis: neuroendoscopic findings and
      management.

PMID- 21965704
TI  - Catastrophic antiphospholipid antibody syndrome with bone marrow necrosis: a rare
      complication.

PMID- 21965705
TI  - Polychondritis associated with chronic hepatitis C virus infection.

PMID- 21965706
TI  - Large-vessel giant cell arteritis presenting as back pain with vertebral body
      infarction in a 73-year-old caucasian woman.

PMID- 21965707
TI  - Onset of inflammatory eye disease under tocilizumab treatment for rheumatologic
      conditions: a paradoxical effect?

PMID- 21965708
TI  - The role of the pediatrician in preventing congenital malformations.
AB  - * The development of new knowledge and new diagnostic techniques and technology
      as well as the sophistication of epidemiology studies and maturation of the
      fields of clinical genetics and clinical teratology have revolutionized the field
      of reproductive and developmental biology.* Advances have enabled physicians and
      scientists to determine the causes of developmental abnormalities and, therefore,
      discover methods of prevention. The process of evaluation is based on the
      knowledge base developed over the past 50 years.* Although genetic abnormalities
      are responsible for a significant proportion of reproductive and developmental
      deleterious effects, a larger proportion of these effects are due to unknown
      causes.* Environmental causes are less frequent, although many of the
      environmental effects as well as many of the genetic effects can be prevented
      through genetic counseling and preconceptual planning. Effective treatment and
      amelioration of developmental effects also have improved.* More than 50
      environmental drugs, chemicals, maternal diseases, infections, nutritional
      abnormalities, and physical agents can affect reproduction deleteriously and
      result in CMs.Theoretically, all these causes are preventable.* Throughout the
      developing world, the addition of folic acid and iodine could prevent tens of
      thousands of birth defects and developmental abnormalities.* In the United
      States, the opportunity for prevention can be introduced at the population level
      and by addressing individual patients' clinical problems.* If a mother of a
      malformed infant had some type of exposure during pregnancy, such as a diagnostic
      radiologic examination or medication, the consulting physician should not support
      or suggest the possibility of a causal relationship before performing a complete
      evaluation. If a pregnant woman who has not yet delivered had some type of
      exposure during pregnancy, the consulting physician should not support or suggest
      the possibility that the fetus is at increased risk before performing a complete
      evaluation. * Every patient deserves a complete, scholarly evaluation that uses
      the basic principles of teratology and risk analysis.

PMID- 21965709
TI  - Group A streptococcal infections.
AB  - * GAS is a common cause of upper respiratory tract and skin infections.* Based on
      strong research evidence, (1) throat culture is the gold standard for diagnosing
      GAS pharyngitis.* Based on strong research evidence, (1) oral penicillin V K is
      the antibiotic treatment of choice for GAS pharyngitis because of its efficacy,
      safety, and narrow spectrum.* Based on strong research evidence, (2) primary
      prevention of complications of GAS such as ARF involves prompt diagnosis and
      antibiotic treatment of GAS pharyngitis.* GAS nonsuppurative and suppurative
      complications may occur and are mediated by interactions between GAS antigens or
      exotoxins and the patient's immunesystem.

PMID- 21965710
TI  - Unintentional injuries in pediatrics.
AB  - * Injuries are the leading killer of children.* A variety of host factors
      contribute to different types of injury.* Motor vehicles remain the biggest
      threat.* Both active and passive preventive strategies are necessary to prevent
      injuries.* For maximal safety effectiveness, physicians must be active in their
      communities.

PMID- 21965711
TI  - Anxiety and separation disorders.
AB  - * Based on strong research evidence, anxiety disorders are the most common
      psychiatric illness in children and adolescents. * Based on some research
      evidence, the neurobiology of anxiety disorders is linked to dysregulation in the
      fear and stress response system in the brain. * Based on strong research
      evidence, separation anxiety disorder is one of the most common causes of school
      refusal, and addressing both the function of the behavior and returning to school
      as soon as possible is recommended. (7)* Based on strong research evidence, CBT
      is the first-line treatment for anxiety disorders in children and adolescents. *
      Based on strong research evidence, SSRIs are effective for treatment of moderate
      to-severe anxiety disorders in children and adolescents.

PMID- 21965712
TI  - Index of Suspicion * Case 1: Voiding difficulty in a 10-year-old * Case 2:
      Seizure-like activity precipitated by loud noise in a 2-year-old * Case 3:
      purplish-brown, shiny upper extremity lesion and stiff hand in a 9-year-old.

PMID- 21965713
TI  - Media role in violence and the dynamics of bullying.

PMID- 21965715
TI  - Visual diagnosis: respiratory distress: a great masquerader.

PMID- 21965716
TI  - Autologous stem cell transplantation: leukapheresis product has anti-angiogenic
      effects in vivo correlating with neutrophil-derived VEGFR1.
AB  - BACKGROUND: High-dose chemotherapy (HDC) followed by autologous stem cell
      transplantation (ASCT) is used for the treatment of hemato-oncologic
      malignancies. In this study, we measured the effect of HDC/ASCT on plasma
      concentrations of antiangiogenic soluble vascular endothelial growth factor
      receptor 1 (sVEGFR1) and of leukapheresis products (LP) and patient serum on
      chick chorioallantoic (CAM) angiogenesis. MATERIALS AND METHODS: VEGFR1- and CD34
      expressing cells of leukapheresis products were analyzed by flow cytometry.
      Alternatively spliced isoforms of VEGFR1 mRNA were quantified using reverse
      transcription PCR. RESULTS: Plasma concentrations of sVEGFR1 decreased after HDC,
      but significantly increased after ASCT. In the CAM assay, sera of patients
      elicited a proangiogenic effect before and after HDC, but a strong antiangiogenic
      response after ASCT, comparable to that of bevacizumab at therapeutic
      concentrations. LP contains high concentrations of sVEGFR1, and high density of
      VEGFR1(+) neutrophilic granulocytes, in which mRNA expression is shifted toward
      the soluble VEGFR1 isoform. CONCLUSION: Neutrophil-derived antiangiogenic sVEGFR1
      within the LP may contribute to the therapeutic efficacy of ASCT.

PMID- 21965717
TI  - A rapid imageable in vivo metastasis assay for circulating tumor cells.
AB  - Circulating tumor cells (CTCs) are of great importance for cancer diagnosis,
      prognosis and treatment. It is necessary to improve the ability to image and
      analyze them for their biological properties which determine their behavior in
      the patient. In the present study, using immunomagnetic beads, CTCs were rapidly
      isolated from the circulation of mice orthotopically implanted with human PC-3
      prostate cancer cells stably expressing green fluorescent protein (GFP). The PC-3
      GFP CTCs were then expanded in culture in parallel with the parental PC-3-GFP
      cell line. Both cell types were then inoculated onto the chorioallentoic membrane
      (CAM) of chick embryos. Eight days later, embryos were harvested and the brains
      were processed for frozen sections. The IV-100 intravital laser scanning
      microscope enabled rapid identification of fluorescent metastatic foci within the
      chick embryonic brain. Inoculation of embryos with PC-3-GFP CTCs resulted in a 3
      to 10-fold increase in brain metastasis when compared to those with the parental
      PC-3-GFP cells (p<0.05 in all animals). Thus, PC-3-GFP CTCs have increased
      metastatic potential compared to their parental counterparts. Furthermore, the
      chick embryo represents a rapid, sensitive, imageable assay of metastatic
      potential for CTCs. The chick embryo assay has future clinical application for
      individualizing patient therapy based on the metastatic profile of their CTCs.

PMID- 21965718
TI  - EBP1 inhibits translation of androgen receptor mRNA in castration resistant
      prostate cancer cells.
AB  - BACKGROUND: Therapies that inhibit androgen receptor (AR) are needed for
      treatment of castration-resistant prostate cancer (CRPC). The ErbB3 binding
      protein 1 (EBP1) reduces protein expression of both AR and its target genes in
      CRPC. Although EBP1 regulates AR in hormone-sensitive prostate cancer cells, by
      both destabilizing AR mRNA and inhibiting protein translation, the mechanism of
      EBP1 down regulation of AR in CRPC is unknown. MATERIALS AND METHODS: Western
      blot and quantitative PCR analysis of cell lysates and polysomes were used to
      assess AR mRNA, protein expression and translation. RESULTS: In contrast to
      hormone- dependent cells, EBP1 did not change steady state levels of AR mRNA or
      AR mRNA stability in hormone refractory cells. EBP1 did slow protein translation
      of AR mRNA. The ErbB3/4 ligand heregulin further diminished AR translation in
      EBP1 -transfected cells, but not in control cells. CONCLUSION: These studies
      suggest that one pathway of EBP1 down-regulation of AR levels may be lost in
      CRPC.

PMID- 21965719
TI  - FISH scoring on paraffin sections versus single-cell suspension for chromophobe
      renal carcinoma and renal oncocytoma.
AB  - BACKGROUND: Sectioning of the nuclei on tissue sections may give an overestimate
      of monosomy, a feature diagnostic of chromophobe renal cell carcinoma versus
      renal oncocytoma. The aim of the study was to assess whether or not nuclear
      sectioning may distort the results obtained from interphase fluorescence in situ
      hybridization (FISH) comparing the data obtained from analysis of isolated nuclei
      derived from formalin-fixed, paraffin-embedded sections with histological
      sections from the adjacent sections from the same tumors. PATIENTS AND METHODS:
      Five chromophobe renal cell carcinomas and five renal oncocytomas were recruited.
      Sections of 5 MUm and 30 MUm were cut for FISH to investigate chromosomes 1, 2, 6
      10 and 17. RESULTS: FISH of isolated nuclei from renal oncocytomas showed a mean
      increase of 3.0% for nuclei with two signals when compared to tissue sections.
      For chromosomes 2, 6, 10 and 17, isolated nuclei showed a mean increase of 4.9%
      of fluorescent signals over nuclei from tissue sections. FISH analysis of
      isolated nuclei from chromophobe renal cell carcinoma showed a similar counts.
      CONCLUSION: When a tumor section exhibits a borderline percentage of nuclei with
      single signals around the cut-off level on tissue sections, the test should be
      repeated on isolated nuclei to confirm chromosomal loss, diagnostic of
      chromophobe renal carcinoma.

PMID- 21965720
TI  - In vitro evaluation of targeted antisense 177Lu radiotherapy.
AB  - BACKGROUND: The BCL2 proto-oncogene in non-Hodgkin's lymphoma is a dominant
      inhibitor of apoptosis. The goal of this work was to develop a (177)Lu-labeled
      anti-BCL2-peptide nucleic acid (PNA) conjugate designed for dual modality NHL
      therapy, i.e., simultaneous down-regulation of BCL2-mediated resistance to
      apoptosis and delivery of cytotoxic internally emitted radiation. MATERIALS AND
      METHODS: The effect of 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetra-acetic
      acid (DOTA)-anti-BCL2-Tyr(3)-octreotate was evaluated by uptake, efflux,
      proliferation, and viability assays, using Mec-1 lymphoma cells. In vitro
      dosimetry was modeled with a Monte Carlo projection. RESULTS: Cellular efflux
      indicated moderate retention of radioactivity in the Mec-1 cells. Viability
      studies using the (177)Lu-labeled PNA conjugate indicated a mass-dose dependence
      and strongly additive statistical effect in reducing cellular viability.
      CONCLUSION: These studies demonstrate the ability of a BCL2 antisense PNA
      conjugate to specifically target, be retained in, and reduce cellular viability
      in Mec-1 NHL cells. The results also hold promise for the development of a
      therapeutic radiopharmaceutical with potential dual modality function.

PMID- 21965721
TI  - Cyclin B1 expression and p53 status in squamous cell carcinomas of the head and
      neck.
AB  - BACKGROUND: The cyclin B1/CDC2 complex governs entry into mitosis by regulating
      the G(2)/M checkpoint, and it can be repressed by the tumor suppressor p53. We
      aimed to determine cyclin B1 expression in squamous cell carcinomas of the head
      and neck (SCCHN) and correlate it with p53 status and clinicopathological
      parameters. PATIENTS AND METHODS: Cyclin B1 and p53 protein expression was
      analyzed by immunohistochemistry, and p53 mutation analyses were performed.
      RESULTS: Cytoplasmic expression of cyclin B1 was found in all 26 SCCHN studied.
      In contrast, nuclear staining was seen in the basal layers of normal mucosa. A
      total of 46% of tumors showed high cyclin B1 expression. p53 was overexpressed in
      53.8% of cases, and of these 79% carried a p53 gene mutation. High cyclin B1
      expression significantly correlated with the high tumor grade, but not with
      gender, tumor size, nodal status, local tumor recurrence or p53 expression.
      CONCLUSION: Cyclin B1 is frequently overexpressed in SCCHN, and its high
      expression is significantly associated with a high tumor grade. These data
      suggest that cyclin B1 may serve as a potential prognostic biomarker in SCCHN.

PMID- 21965723
TI  - Anticancer activity of branched-chain derivatives of oleic acid.
AB  - BACKGROUND: A number of unsaturated fatty acids and a few saturated branched
      chain fatty acids have been reported to exhibit anticancer activity. MATERIALS
      AND METHODS: In previously reported research, several novel branched-chain
      derivatives (methyl, n-butyl, phenyl) of methyl oleate were produced by
      bromination in the allylic position and subsequent treatment with organocuprate
      reagents. These compounds and their free acid counterparts were tested in vitro
      for their antiproliferative activities against two cancer cell lines: MCF-7
      (human breast) and HT-29 (human colon). In addition, two sets of isomeric
      tertiary alcohols obtained as side-products in the synthesis of the branched
      chain derivatives were evaluated. Testing was performed at three concentration
      levels (50, 100, and 200 ppm) in dimethyl sulfoxide (DMSO). RESULTS: The greatest
      growth inhibitory activity was exhibited by the branched phenyl derivative of
      oleic acid, with IC(50) at 48 ppm against both MCF-7 and HT-29. The branched n
      butyl derivative of oleic acid also exhibited significant antiproliferative
      activity, with IC(50) at 82 ppm against MCF-7 and 77 ppm against HT-29.
      CONCLUSION: The observed potent anticancer activity of the n-butyl and phenyl
      derivatives indicates that certain synthetic branched-chain unsaturated fatty
      acids have potential in the treatment of cancer and further research is
      warranted.

PMID- 21965722
TI  - TGF-beta regulation of focal adhesion proteins and motility of premalignant oral
      lesions via protein phosphatase 1.
AB  - Premalignant oral lesions have a high incidence of recurrence and progression to
      malignant disease and, although studies have shown the contribution of
      transforming growth factor beta (TGF-beta) to cancer progression, none have been
      conducted with premalignant oral lesion cells to determine the impact of TGF-beta
      in stimulating properties that are characteristic of more invasive cells. The
      present study focused on TGF-beta-modulation of paxillin and the serine/threonine
      protein phosphatase PP-1, and the impact on cellular motility. These studies show
      that TGF-beta stimulates premalignant lesion cell motility and up regulates
      expression of paxillin, as well as its co-localization with PP-1, while
      concurrently diminishing the level of paxillin serine phosphorylation. The TGF
      beta-mediated up regulation of paxillin and co-localization with actin, as well
      as the TGF-beta-stimulated motility of premalignant lesion cells, were all
      blocked by inhibiting PP-1, indicating their dependence on PP-1 activity. These
      studies suggest interplay between TGF-beta and PP-1 in promoting a more malignant
      phenotype in premalignant oral lesion cells.

PMID- 21965724
TI  - Enhanced efficacy of gemcitabine by indole-3-carbinol in pancreatic cell lines:
      the role of human equilibrative nucleoside transporter 1.
AB  - Pancreatic cancer patients treated with gemcitabine (2',2'-difluorodeoxycytidine)
      can eventually develop resistance. Recently, published data from our laboratory
      demonstrated enhanced efficacy of gemcitabine with the dietary agent, indole-3
      carbinol (I3C). The current study examined the possible mechanism for this I3C
      enhanced efficacy. Several pancreatic cell lines (BxPC-3, Mia Paca-2, PL-45, AsPC
      1 and PANC-1) were examined for modulation of human equilibrative nucleoside
      transporter 1 (hENT1) expression, the major transporter for gemcitabine, by I3C
      alone and combined with gemcitabine. I3C significantly (p<0.01) up-regulated
      hENT1 expression in several cell lines. Gemcitabine alone showed no effect on
      hENT1 expression. However, combining gemcitabine with I3C further increased hENT1
      expression. Cell viability assays revealed no effect of I3C on normal cells,
      hTERT-HPNE. hENT1-specific inhibitor, nitrobenzylthioinosine, significantly
      abrogated I3C-induced gemcitabine cytotoxicity, further demonstrating its
      specificity. This study demonstrates that up-regulation of hENT1 expression may
      be a novel mechanism involved in the additive effect of I3C and gemcitabine.

PMID- 21965725
TI  - Silencing of selected glutamate receptor subunits modulates cancer growth.
AB  - BACKGROUND: Emerging evidence supports a role for glutamate in the biology of
      cancer. We studied the impact of glutamate receptor subunit silencing on cancer
      phenotype. MATERIALS AND METHODS: Different fragments of the coding region for
      ionotropic glutamate receptor AMPA 4 (GLUR4), ionotropic glutamate receptor N
      methyl D-aspartate 1 (NR1), ionotropic glutamate receptor kainate 5 (KA2) and
      ionotropic glutamate receptor N-methyl D-aspartate 2D (NR2D) were stably
      transfected into human TE671, RPMI8226 and A549 cell lines. Resulting changes in
      cell proliferation, migration and mRNA expression of genes that determine cancer
      phenotype were assayed. RESULTS: Decreased expression of GLUR4 markedly increased
      cancer cell proliferation, whereas decreased expression of NR1 markedly reduced
      the propensity of cancer cells to proliferate. Knockdown of KA2 and NR2D did not
      influence cancer phenotype. Gene silencing of GLUR4 modulated the mRNA expression
      of various genes in these cancer cell lines, as determined with the Human Cancer
      PathwayFinderTM PCR Array. Knockdown of GLUR4 influenced the expression and
      function of genes involved in invasion and metastasis, tumour suppressor genes,
      oncogenes and adhesion genes. CONCLUSION: The findings suggest that glutamate
      receptor subunits on cancer cells are linked to biochemical pathways that
      regulate malignant phenotype.

PMID- 21965727
TI  - Metastasis suppressor-1, MTSS1, acts as a putative tumour suppressor in human
      bladder cancer.
AB  - BACKGROUND: Metastasis suppressor 1 (MTSS1) is proposed to function as a
      cytoskeletal-associated protein, which may play a role in the aggressiveness of
      cancer cells. Recent studies have demonstrated a clinical significance of MTSS1
      in certain types of cancer, but its role in bladder cancer remains unknown. We
      investigated the expression of MTSS1 in normal and malignant human bladder
      tissues and its molecular interaction within bladder cancer cells. MATERIALS AND
      METHODS: The expression of MTSS1 in human bladder tissues and bladder cancer cell
      lines was assessed at both the mRNA and protein levels using reverse
      transcription-PCR (RT-PCR) and immunohistochemistry, respectively. Full-length
      MTSS1 cDNA was amplified from normal mammary tissues. The effect of MTSS1
      overexpression on cellular functions was examined in bladder cancer cells using a
      variety of in vitro assays. RESULTS: Transitional cells of bladder tissues
      stained positively for MTSS1. However, cancer cells from tumour tissues did not
      stain for MTSS1. Similarly, in bladder cancer cell lines, MTSS1 was almost absent
      from T24 and RT112 cells, and the EJ138 cell line expressed a very low level of
      MTSS1. Overexpression of MTSS1 reduced the growth and adhesion of bladder cell
      lines in vitro. However, overexpression of MTSS1 had no bearing on the invasion
      and migration of bladder cell lines in vitro. CONCLUSION: MTSS1 is expressed at
      low levels or is absent from human bladder cancer cells. MTSS1 levels are
      inversely correlated with the growth and adhesion of bladder cancer cells in
      vitro. MTSS1 appears to be a potential tumour suppressor in human bladder cancer.

PMID- 21965726
TI  - Paclitaxel and TRAIL synergize to kill paclitaxel-resistant small cell lung
      cancer cells through a caspase-independent mechanism mediated through AIF.
AB  - BACKGROUND: Small cell lung cancer (SCLC) is the most aggressive form of lung
      cancer with poor disease outcome. The chemotherapeutic agent paclitaxel (PA) is
      commonly used as a second-line treatment in SCLC, but response rates are low.
      MATERIALS AND METHODS: 86M1 SCLC cells were treated in the presence or absence of
      paclitaxel and TRAIL or the combination for 24 hours. Western blot analysis was
      utilized to examine protein expression, cell surface protein expression and
      membrane integrity were elucidated by flow cytometry, and immunofluorescence
      microscopy was used to demonstrate translocation of proteins to the cell nucleus.
      RESULTS: Human 86M1 SCLC cells were found to be resistant to PA killing in vitro.
      This resistance is mediated by up-regulation of pro-survival protein BCL-xl.
      However, PA also increases surface expression of death receptors 4 and 5 (DR4 and
      DR5, respectively). The death receptors' ligand increased SCLC killing by PA
      through an apparent caspase-independent route involving activation/translocation
      of AIF. CONCLUSION: The addition of TRAIL to PA can potentiate apoptosis in a
      relatively PA-resistant SCLC line (specifically 86M1 cells). More importantly, we
      are the first to report an active method of resistance to paclitaxel in SCLC via
      BCL-xl up-regulation.

PMID- 21965728
TI  - Cytotoxicity of chalcone derivatives towards glioblastoma.
AB  - BACKGROUND: Among seventeen compounds derived from chalcones investigated as
      potential anticancer drugs towards LN229 glioblastoma cell line, only two were
      effective. MATERIALS AND METHODS: Anticancer activity was investigated by
      evaluating the cell growth, cell cycle, mitotic index and the cell death.
      RESULTS: Two compounds, namely C2 and C12, inhibited cell proliferation
      associated with a blockade in the G(2)/M phase of the cell cycle and arrested the
      growth of tumour spheroid mimicking in vivo tumour. C2 blocked cells in the G(2)
      phase whereas C12 blocked cells in the M phase of the cell cycle. C12 and C2
      killed 40% and 95% of the cells respectively using complex mechanisms. The two
      compounds increased the fluorescence of rhodamine-123 and N-acetylcysteine
      inhibited their activity, suggesting a role for reactive oxygen species in cell
      death mediated by these two compounds. CONCLUSION: C2 and C12 are markedly
      cytostatic and cytolytic to glioblastoma cells and act through different
      pathways.

PMID- 21965729
TI  - Breast cancer cell-derived cytokines, macrophages and cell adhesion: implications
      for metastasis.
AB  - BACKGROUND: Liver metastasis is associated with a proinflammatory
      microenvironment and up-regulation of cell adhesion molecules expressed by
      endothelial cells. The aim of this study was to characterize the interrelations
      between breast cancer cell-secreted cytokines, macrophages and E-selectin
      mediated cancer cell adhesion and their role in metastasis of breast cancer.
      MATERIALS AND METHODS: Three metastatic breast cancer cell lines (1590, KM22, ZE)
      were studied. Cell culture supernatants were screened for cytokines and the
      potential for cytokines to increase tumor-necrosis factor-alpha (TNF-alpha)
      production by ANA-1-macrophages was analyzed. E-Selectin-mediated tumor cell
      adhesion of fluorescence labelled tumor cells was evaluated by measurement of
      fluorescence intensity with and without E-selectin-blocking strategies
      (monoclonal antibodies, cimetidine). RESULTS: Tumor-specific cytokine secretion
      patterns were revealed. TNF-alpha secretion from cultured macrophages increased
      after incubation with tumor supernatants. Tumor cell adhesion was significantly
      inhibited by cimetidine and monoclonal antibodies against E-selectin (KM22 with
      cimetidine, p<0.05). CONCLUSION: Breast cancer cell-secreted cytokines stimulate
      macrophages to produce TNF-alpha, a known up-regulator of E-selectin expression,
      and therefore cell adherence to endothelium. Inhibition of this mechanism could
      be an attractive therapeutic option for the prevention of breast cnacer
      metastasis.

PMID- 21965731
TI  - The role of the 3D environment in hypoxia-induced drug and apoptosis resistance.
AB  - BACKGROUND: 3D tumors express different adhesion receptors from those expressed
      in monolayers, leading to a distinct microenvironment. The third dimension also
      brings mass transport into relevance, as inadequate diffusion of oxygen produces
      hypoxia. This study investigates the effects of distinct 3D environments on
      hypoxia-associated apoptosis and drug resistance. MATERIALS AND METHODS: Under
      hypoxia and normoxia, U251 glioma cells and U87 astrocytoma cells were grown as
      spheroids on flat substrates, scaffolds seeded with dispersed cells, and spheroid
      seeded scaffolds. The samples were subsequently treated with doxorubicin and
      resveratrol, known inducers of apoptosis. RESULTS: All 3D environments induced
      increased but distinct resistance to apoptosis, as evident by lower caspase-3
      activity, and higher production of anti-apoptotic proteins BCL-2 and survivin.
      Hypoxic monolayers also exhibited higher resistance to doxorubicin and higher
      production of basic fibroblast growth factor (bFGF) and vascular endothelial
      growth factor (VEGF), but lower production of BCL-2 and survivin. CONCLUSION:
      These findings suggest that in vitro, 3D models acquire greater apoptosis
      resistance via up-regulation of anti-apoptotic proteins, and that the precise
      mechanism depends on the individual 3D microenvironment.

PMID- 21965730
TI  - Intracellular metabolism, subcellular localization and phototoxicity of HMME/HB
      in ovarian cancer cells.
AB  - BACKGROUND: Photodynamic therapy (PDT) is considered a promising new strategy for
      ovarian cancer treatment. As the key component in PDT, photosensitizer metabolism
      and localization in cancer cells is particularly important. MATERIALS AND
      METHODS: The localization of the photosensitizers hematoporphyrin monomethyl
      ether (HMME) and hypocrellin B (HB) were determined in the ovarian cancer cell
      lines SKOV3 and NuTu-19 by fluorescence microscopy and laser scanning confocal
      microscopy(LSCM). A JD801 image analysis system was used to analyze the
      fluorescence intensity of the photosensitizers in the cells. The phototoxicity of
      both drugs to the cancer cells was determined by MTT assay. RESULTS: Both
      photosensitizers were mainly distributed in the cytoplasm. Drug uptake reached a
      peak after 4 h incubation with HB and after 3 h incubation with HMME. Within a
      certain range, the higher the concentration, the stronger the fluorescence became
      and at 40 MUg/ml, the intracellular photosensitizer had reached saturation. Based
      on these results PDT was applied to SKOV3 cells. All the cells were killed when
      the photosensizer dose reached 40 MUg/ml. CONCLUSION: PDT is an effective therapy
      for ovarian cancer cells.

PMID- 21965732
TI  - Anticancer SAR models for MCF-7 and MDA-MB-231 breast cell lines.
AB  - The National Cancer Institute's Developmental Therapeutics Program (DTP)
      maintains the screening results obtained in 60 standardized cancer cell lines for
      ~43,000 compounds. Here the application of the categorical structure-activity
      relationship (cat-SAR) program for the identification of the structural
      attributes of identified compounds that display differential cytostatic or
      cytotoxic activity to one breast cancer cell line and not another is reported.
      The goal of this approach is to separate features associated with
      antiproliferative activity towards many cell lines from those that affect only a
      specific cell type. To assess this approach, SAR models were developed for
      cytostatic and cytotoxic activity against the human breast cancer cell lines MCF
      7 and MDAMB-231 and three differential activity models for compounds that were
      potent cytostatic and cytotoxic agents in MCF-7 cells, but relatively inactive
      against MDA-MB-231 cells. The MCF-7 and MDA-MB-231 models comprised the most
      potent 200 active and least potent 200 inactive compounds found in the DTP
      database and the differential activity models comprised 200 compounds potent in
      one cell line and not the other and 200 compounds equally potent between the cell
      lines. Leave-one-out validations of the individual MCF-7 and MDA-MB-231 models
      returned values between 83 and 85% concordance, with values obtained between 66
      and 76% concordance for the differential activity models. The cat-SAR approach
      identified the chemical attributes associated with cytostatic and cytotoxic
      activity for the MCF-7 and MDA-MB-231 breast cancer cell lines included in the
      DTP and furthermore, were able to differentiate the selective activity of
      compounds between the two breast cancer lines. Thus it is conceivable that such
      cell line-specific mechanisms could be exploited for the discovery of highly
      specific anti-breast cancer agents and could also potentially facilitate the
      development of SAR models with sufficient resolution and clarity to identify
      chemical moieties associated with antiproliferative activity towards selective
      individual cancer types while being innocuous to other cell types.

PMID- 21965733
TI  - Down-regulation of EGFR prolonged cell growth of glioma but did not increase the
      sensitivity to temozolomide.
AB  - BACKGROUND: Malignant glioma is an invasive disease of the central nervous
      system. One of the factors that regulate growth of these tumors is expression of
      epidermal growth factor receptor (EGFR) in the cells. This study investigated the
      effects of down-regulation of EGFR on cell proliferation, cell cycle and
      cytotoxicity to antineoplastic agent. MATERIALS AND METHODS: A short hairpin RNA
      transcription vector targeting EGFR was transfected into KNS42 cells. Growth
      curve, cell cycle and sensitivity to temozolomide of the cells were assessed.
      RESULTS: Transfection inhibited EGFR expression by 50.5%. It prolonged cell
      doubling time by 25.7%. However, it did not meaningfully alter the cell cycle
      populations nor increase sensitivity to temozolomide. CONCLUSION: Suppressing
      expression of EGFR inhibited cell proliferation. However, unlike PTEN expression
      or ROCK1 down-regulation, it did not alter the cell cycle or increase sensitivity
      to temozolomide.

PMID- 21965734
TI  - Fluvastatin enhances sorafenib cytotoxicity in melanoma cells via modulation of
      AKT and JNK signaling pathways.
AB  - Most metastatic melanomas are refractory to current available therapy,
      underscoring the need to identify new effective treatments. Sorafenib, a
      multikinase inhibitor of the mitogen-activated protein kinase signaling pathway,
      showed promise in earlier stages of clinical development, but ultimately failed
      to demonstrate efficacy as a single agent in the treatment of melanoma. In order
      to enhance the efficacy of sorafenib in the treatment of melanoma, we tested over
      2,000 naturally occurring compounds and marketed drugs in the presence of
      sorafenib in chemoresistant human melanoma cell lines also resistant to sorafenib
      induced apoptosis. Of the 9 compounds identified as sorafenib sensitizers, we
      prioritized the cholesterol-lowering agent fluvastatin, based on its favorable
      pharmacokinetics and safety profile. Our results demonstrate that fluvastatin at
      1 MUM, a level safely achieved through oral administration, dramatically enhances
      the growth-inhibitory activity of clinically achievable concentrations of
      sorafenib in M14 and SKM-173 melanoma cells, with a 3.2- and 3.6-fold reduction
      in sorafenib 50% growth inhibition (GI50), respectively. Similar effects were
      observed for other melanoma cell lines. Combination indices analysis revealed a
      synergistic relationship between the two agents. Fluvastatin enhances sorafenib
      mediated apoptosis as revealed through enhanced cleavage of poly (ADP-ribose)
      polymerase. In combination with sorafenib, fluvastatin treatment results in
      reduced levels of activated murine thymoma viral oncogene homolog along with
      enhanced levels of activated c-Jun N-terminal kinase. Sensitization to sorafenib
      is unique to fluvastatin, as other statins (pravastatin and simvastatin) do not
      enhance sorafenib-mediated growth inhibition. These promising results warrant
      further investigation into the clinical applicability of fluvastatin as an agent
      for enhancing the efficacy of sorafenib in the treatment of melanoma.

PMID- 21965735
TI  - Epigenetic modifiers exert renal toxicity through induction of p66shc.
AB  - BACKGROUND/AIMS: Trichostatin A (TSA) and 5-azacytidine (5AZA) induce reactive
      oxygen species (ROS)-mediated injury in renal proximal tubule cells. Since TSA
      and 5AZA are activators of p66shc, we questioned whether p66shc may mediate renal
      toxicity of TSA- and 5AZA. MATERIALS AND METHODS: Renal proximal tubule cells
      were treated with either TSA or 5AZA for 24 hours followed by treatment with 200
      MUM H(2)O(2). Expression of p66shc and activity of its promoter, as well as its
      mitochondrial and cytochrome c binding were determined. Impact of knockdown of
      p66shc and mutation of its cytochrome c-binding site on ROS production and cell
      injury was studied. RESULTS: TSA, and 5AZA increased expression of p66shc through
      induction of its promoter and also increased its mitochondrial/cytochrome c
      binding. Knockdown or mutation of the cytochrome c binding site of p66shc
      attenuated ROS production and cell injury. CONCLUSION: Therapeutic means that
      interfere with induction of p66shc may ameliorate renal toxicity of those
      epigenetic modifiers.

PMID- 21965736
TI  - Oncostatin M and IL-6 induce u-PA and VEGF in prostate cancer cells and correlate
      in vivo.
AB  - BACKGROUND/AIM: Oncostatin M (OSM) and interleukin-6 (IL-6) are growth factors
      for prostate cancer (PC). Vascular endothelial growth factor (VEGF) and urokinase
      type plasminogen-activator (u-PA) have been implicated in tumour progression. A
      possible interaction between IL-6, OSM, u-PA and VEGF in PC was investigated.
      MATERIALS AND METHODS: Primary prostate epithelial cells (PPEC) and DU-145 PC
      cells were treated with IL-6 or OSM and the effects on u-PA and VEGF expression
      were studied. Plasma levels of IL-6, OSM, u-PA and VEGF were determined in
      patients with or without PC. RESULTS: In DU-145 cells, OSM and IL-6 up-regulated
      u-PA and VEGF significantly. Higher levels of IL-6 and OSM in metastasising PC
      than in nonmetastasising PC and benign prostatic hyperplasia (BPH) and
      correlations between IL-6, OSM, u-PA and VEGF were found. CONCLUSION: OSM and IL
      6 increase u-PA and VEGF in DU-145 cells but not in PPEC and possibly, by
      promoting matrix degradation and angiogenesis, could play a role in the
      pathogenesis of prostate cancer.

PMID- 21965737
TI  - Prevention of mouse lung tumors by combinations of chemopreventive agents using
      concurrent and sequential administration.
AB  - BACKGROUND: Concurrent and sequential administration of combinations of
      budesonide, bexarotene, suberoylanilide hydroxamic acid (SAHA) and atorvastatin
      were evaluated in A/J mice for prevention of lung tumors initiated by 4
      (methylnitrosoamino)-1-(3-pyridyl)-1-butanol, NNK). MATERIALS AND METHODS:
      Individual drugs and their combinations were administered for 26 weeks after NNK
      initiation. For sequential administration, budesonide was given for 21 weeks
      followed by a second drug. RESULTS: Alone, budesonide, bexarotene, and SAHA
      caused a significant decrease in total and large tumors at 21 and 26 weeks.
      Concurrent treatment with budesonide and bexarotene or SAHA caused a
      significantly greater decrease in total tumors and large tumors than either drug
      administered alone. Sequential administration of all combinations (except
      budesonide/atorvastatin) gave a significant reduction in total and large tumors.
      Budesonide followed by SAHA and SAHA with atorvastatin yielded a greater
      reduction in large tumors. CONCLUSION: Combinations of drugs demonstrated a
      greater efficacy in preventing mouse lung tumors than did the individual agents.

PMID- 21965738
TI  - Modulation of multidrug efflux pump activity by new hydantoin derivatives on
      colon adenocarcinoma cells without inducing apoptosis.
AB  - BACKGROUND: Hydantoin derivatives are very promising candidates to improve the
      efficacy of anticancer chemotherapy. Previously, we demonstrated that eight
      hydantoin derivatives inhibited the P-glycoprotein (ABCB1) efflux pump of mouse T
      lymphoma cells, as well as acting synergistically with the anticancer drug
      doxorubicin. MATERIALS AND METHODS: The activity of the hydantoin derivatives
      were investigated in another MDR cancer model, namely Colo 205/S sensitive and
      Colo 320/R resistant colon carcinoma cells respectively, having normal or
      overexpressed ABCB1 systems. RESULTS: Among the hydantoin derivatives evaluated,
      BS-1, MN-3 and JH-63 were the most effective ABCB1 transporter inhibitors at the
      concentration of 4 mg/l on the Colo 320/R cells, compared to the positive
      control, verapamil. CONCLUSION: The derivatives did not induce apoptosis of Colo
      320/R resistant colon carcinoma cells, indicating that these hydantoin compounds
      are potent efflux pump inhibitors (EPI) without affecting the signalling pathways
      that regulate apoptosis.

PMID- 21965739
TI  - Polo-like kinase 1 inhibition as a new therapeutic modality in therapy of
      cholangiocarcinoma.
AB  - BACKGROUND: Cholangiocarcinoma (CC) is highly resistant to chemotherapy and
      radiation, and is, therefore, difficult to cure. Polo-like kinases (Plks) are
      increasingly recognized as key regulators of mitosis, meiosis and cytokinesis.
      Alterations in PLK1- expression have been brought into relation with
      tumorigenesis, thus rendering PLK1 suppression an interesting target for tumor
      therapy. BI 2536, the first compound of the chemical class of
      dihydropteridinones, is a highly selective and potent inhibitor of PLK1.
      MATERIALS AND METHODS: Retardation of cell proliferation by BI 2536 was tested in
      14 CC cell lines by cell viability assay. Moreover, molecular activity of BI 2536
      was investigated by Western blot, flow cytometry and real time- polymerase chain
      reaction (RT-PCR). Apposition of gemcitabine, 5-fluorouracil (5-FU) and insulin
      like growth factor-1 receptor (IGF-1R) retardant NVP-AEW541 was also examined.
      RESULTS: BI 2536 subdued proliferation in all CC cell lines, however, reaction
      was stronger in gallbladder carcinoma. Therapy with BI 2536 did not result in a
      significant change in phosphorylation of histone H3, AKT, and p42/44. However,
      exposure of cells to this compound caused arrest at the G(2)/M-checkpoint and a
      surge in apoptosis. Moreover, PLK1 and FOXM1 were concurrently present in all
      cell lines, proposing a role for their involvement. Use of a mixture of BI 2536
      with 5-FU or NVP-AEW541 resulted in synergism, while a mixture with gemcitabine
      resulted in additive activity. CONCLUSION: These experiments indicate that BI
      2536 is effective against CC and increases the potency of 5-FU and NVP-AEW541.

PMID- 21965740
TI  - Phytoestrogens induce apoptosis via extrinsic pathway, inhibiting nuclear factor
      kappaB signaling in HER2-overexpressing breast cancer cells.
AB  - BACKGROUND: Phytoestrogens are known to prevent tumor induction. But their
      molecular mechanisms of action are largely unknown. This study aimed to examine
      the effect of genistein and quercetin on proliferation and apoptosis in HER2
      expressing breast cancer cells. MATERIALS AND METHODS: The antiproliferative
      effects of phytoestrogens were tested by proliferation assays. Flow cytometry was
      performed to analyze the cell cycle. The effect of phytoestrogens on cell
      signaling molecules was determined by Western blotting. RESULTS: Genistein and
      quercetin inhibited the proliferation of MCF-7 vec and MCF-7 HER2 cells. This
      growth inhibition was accompanied with an increase of subG(0)/G(1) apoptotic
      fractions. Genistein and quercetin induced extrinsic apoptosis pathway, up
      regulating p53. Genistein and quercetin reduced the phosphorylation level of
      IkappaBalpha, and abrogated the nuclear translocation of p65 and its
      phosphorylation within the nucleus. CONCLUSION: Genistein and quercetin exert
      their antiproliferative activity by inhibiting NFkappaB signaling. Phytoestrogens
      could be potential useful compounds to prevent or treat HER2-overexpressing
      breast cancer.

PMID- 21965741
TI  - Biodistribution of 131I-labeled anti-CK8 monoclonal antibody in HNSCC in
      xenotransplanted SCID mice.
AB  - BACKGROUND: A new promising approach to improve the outcome of head and neck
      squamous cell carcinoma (HNSCC) is the application of radio-labeled antibodies
      directed against tumor-associated antigens. Cytokeratin 8 (CK8), an intermediate
      filament forming protein, is shown to be de novo expressed in dysplastic lesions
      as well as in HNSCC. Therefore like the epithelial cell adhesion molecule CK8
      seems to be a suitable anchor molecule for targeted radioimmunotherapy (RIT). The
      aim of this study was to investigate the biodistribution of a radio-labeled
      Cytokeratin 8-specific monoclonal antibody (mAb) in a SCID (severe combined
      immunodeficiency disease) mouse model. MATERIALS AND METHODS: The mAb against CK8
      was labeled with (131)I and biodistribution was tested in established HNSCC
      xenografts in SCID mice. The biodistribution of the mAb in the tumor and
      different organs was determined with a gamma counter and was calculated as %
      injected dose/gram tissue. RESULTS: Initially, after systemic administration of
      (131)I-anti CK8 monoclonal antibody high activity was seen in all the organs.
      Over time the general activity decreased, whereas activity accumulated in the
      tumor. This activity decayed compared to the other tissues with a two- to
      threefold prolonged radioactive half-life. CONCLUSION: Specific antibody-antigen
      binding is probably responsible for the prolonged radioactive half-life in the
      tumor and the resulting cumulative activity due to enrichment of the (131)I-anti
      CK8 mAb, so that Cytokeratin 8 seems to be a suitable anchor molecule for
      radioimmunotherapy in HNSCC.

PMID- 21965742
TI  - Combination of resveratrol and antiandrogen flutamide has synergistic effect on
      androgen receptor inhibition in prostate cancer cells.
AB  - Agents targeting the androgen receptor (AR) axis are critical for chemoprevention
      and treatment of prostate cancer (PCa) at all stages of the disease. Combination
      molecular targeted therapy may improve overall efficacy. The combination of
      dietary compound resveratrol with known therapeutic agents, such as the
      antiandrogen flutamide, may be particularly attractive due to the pharmacological
      safety of resveratrol. MATERIALS AND METHODS: Resveratrol, 5alpha
      dihydrotestosterone and flutamide were used in various experiments using mostly
      LNCaP cell line. Quantitative reverse transcription polymerase chain reaction
      (qRT-PCR), Western blots, and luciferase assay were utilized to examine the
      levels of AR mRNA, and protein and transcriptional activity in response to
      treatments. Growth proliferation assays were performed in three cell lines
      (LNCaP, PC3 and Du145). RESULTS: Treatment of LNCaP cells with resveratrol (1-100
      MUM) resulted in the inhibition of androgen-promoted growth, inhibition of AR
      transcriptional activity and decrease in the AR and prostate-specific antigen
      protein levels through degradation pathways. The combination of resveratrol with
      flutamide had a synergistic effect on down-regulation of AR. CONCLUSION:
      Resveratrol works in concert with antiandrogen flutamide to reduce the amount and
      activity of AR, suggesting new therapeutic strategies for the treatment of PCa.

PMID- 21965743
TI  - Up-regulation of 42 kDa tubulin alpha-6 chain fragment in well-differentiated
      hepatocellular carcinoma tissues from patients infected with hepatitis C virus.
AB  - We performed proteomic differential display analysis of hepatitis C virus
      associated 21 human hepatocellular carcinoma (HCV-HCC) tissues by using two
      dimensional gel electrophoresis (2-DE) and matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS). One of the
      numerous spots which was located next to three spots of glutamine synthetase
      showed stronger intensity in well-differentiated HCC tissues compared to non
      cancerous tissues. Samples from 6 out of 21 patients showed up-regulation of this
      spot compared to non-cancerous tissues. After in-gel digestion, MALDITOF/MS
      identified the spot as tubulin alpha-6 chain. Two-dimensional immunoblot analysis
      confirmed that this spot was indeed tubulin alpha, and this spot was stronger in
      cancerous tissues than in noncancerous tissues. These results suggest that
      tubulin alpha-6 chain is one of the candidates for biomarkers for well
      differentiated HCV-associated HCC.

PMID- 21965744
TI  - Effects of non-motorized voluntary running on experimental and spontaneous
      metastasis in mice.
AB  - The present study investigated the effects of non-motorized voluntary running on
      experimental metastasis of B16BL/6 melanoma and spontaneous metastasis of Lewis
      lung carcinoma (LLC) in male C57BL/6 mice. After 9 weeks of running, mice (n=30
      per group) received an intravenous injection of B16BL/6 cells or a subcutaneous
      injection of LLC cells, and then they were continued with their running
      activities. Experiments were terminated 2 weeks after the intravenous injection
      of B16BL/6 cells or 2 weeks after surgical removal of the primary tumor from mice
      subcutaneously injected with LLC cells. Mice in the running group ran an average
      of 4-6 km/day for the duration of the experiment. Voluntary running reduced body
      weight compared with the sedentary controls, but there were no differences in the
      number and size of lung metastases between groups with either model. Voluntary
      running significantly reduced plasma insulin and leptin levels and increased
      adiponectin level in mice with and without LLC compared with the sedentary
      controls. Having LLC significantly increased plasma concentrations of vascular
      endothelial growth factor (VEGF), platelet-derived growth factor-BB (PDGF-BB),
      PDGF-AB and monocyte chemotactic protein-1 (MCP-1) in mice. Voluntary running
      significantly increased plasma PDGF-BB and PDGFAB, but not VEGF and MCP-1, in
      mice with LLC compared to their sedentary counterparts. In conclusion, non
      motorized voluntary running was favorable to body weight and the expression of
      related adipokines, but at 4-6 km/day it did not affect either experimental or
      spontaneous metastasis in mice.

PMID- 21965745
TI  - Differential expression of apoptosis, cell cycle regulation and intermediate
      filament genes in oral squamous cell carcinomas associated with toombak use in
      Sudan.
AB  - Previously we used microarray genomic hybridization technology to explore genome
      wide profiles of chromosomal aberrations in samples of oral squamous cell
      carcinomas (OSCCs) and paired normal controls. Based on these findings, 9 genes
      related to apoptosis, cell cycle regulation and intermediate filament proteins
      were selected and their differential expression status was examined by real-time
      quantitative RT-PCR in 26 samples of Sudanese OSCCs and their matched normal
      controls. The findings were correlated with the habit of toombak use. The mRNA
      levels of Bcl2, keratin 1, keratin 13 and p53 were significantly lower and the
      level of survivin was significantly higher in the OSCC samples of the toombak
      users compared to their paired control samples. A significant down-regulation in
      keratin 1 and keratin 13 expression levels was found in the OSCC samples of the
      nontoombak users compared to their normal control samples. The differential
      expression of genes related to apoptosis, cell cycle regulation and types I and
      II keratin could be useful diagnostic markers and provide valuable information
      for the understanding of oral malignancy in relation to toombak use.

PMID- 21965746
TI  - ERas enhances resistance to CPT-11 in gastric cancer.
AB  - BACKGROUND/AIM: We have reported that embryonic stem cell-expressed Ras (ERas) is
      expressed in human gastric cancer and is associated with its tumorigenicity.
      Here, we asked whether ERas plays a role in resistance to chemotherapy in gastric
      cancer. MATERIALS AND METHODS: To assess the cytotoxicity of chemotherapeutic
      agents, ERas-overexpressing human gastric cancer GCIY cells were exposed to
      anticancer agents, including CPT-11 and inhibitor of mammalian target of
      rapamycin (mTOR). We also investigated the mechanisms by which ERas induces
      chemoresistance. RESULTS: ERas-overexpressing clones were significantly more
      resistant to CPT-11 than were the control (p<0.001). Administration of rapamycin
      was significantly cytotoxic to the ERas-overexpressing clones compared with the
      control (p<0.01). Electrophoresis mobility shift assay revealed that ERas
      enhanced nuclear factor (NF)-kappaB activity. PCR array demonstrated that ERas up
      regulated several multidrug efflux transporter genes, including ABCG2.
      CONCLUSION: ERas induces chemoresistance to CPT-11 via activation of
      phosphatidylinositol-3 kinase-protein kinase beta mTOR pathway and NF-kappaB, and
      consequently results in up-regulation of ABCG2.

PMID- 21965747
TI  - Antitumor effect of new HER2 peptide vaccination based on B cell epitope.
AB  - BACKGROUND: While the benefit of passive immunotherapy is commonly accepted,
      active immunization may have advantages for the patient's quality of life. We
      identified a new epitope of Mab CH401 against Her-2/neu extracellular domain (N:
      167-175), and evaluated the effect of active immunization of the 20mer peptide
      containing the epitope (CH401 peptide). MATERIALS AND METHODS: Epitope-mapping
      was performed using ELISA with Her-2/neu-related multiple antigen peptides (MAP).
      BALB/c mice were transplanted with Her-2/neu-expressing lymphoma cell line and
      immunized with the peptides. For monitoring the condition, ELISA and flow
      cytometry was performed. RESULTS: CH401 peptide induced Her-2/neu-specific IgG
      antibody. Tumor growth in immunized mice was suppressed and tumor-infiltrating
      lymphocytes comprised more CD8(+) T-cells, which secreted larger amounts of
      interleukin-2 after the peptide re-stimulation. CONCLUSION: The new Her-2/neu
      peptide contained epitopes for CD4(+) and CD8(+) T-cells, which contributes to
      the suppressive effect on Her-2/neu-expressing tumor cell growth.

PMID- 21965748
TI  - Effects of acute and chronic hypoxia on the radiosensitivity of gastric and
      esophageal cancer cells.
AB  - AIM: The aim of this study was to examine the effects of hypoxia on
      radiosensitivity and to analyze the mechanisms responsible for radiation
      resistance in gastric and esophageal cancer. MATERIALS AND METHODS: A gastric
      cancer cell line, OCUM-12, and an esophageal cancer cell line, TE-6, were used.
      The effects of hypoxia with irradiation on the growth-activity, cell cycle
      distribution, and gene expression were examined. RESULTS: Both acute and chronic
      hypoxia decreased radiosensitivity of cancer cells. The radiosensitivity of
      chronic hypoxic cells was significantly enhanced by reoxygenation. Acute and
      chronic all hypoxia reduced the percentage of cells in the G(2)/M and S phases,
      respectively. In acute hypoxia, the mRNA expression of BRCA1 and BRCA2 was
      reduced in cancer cells. Reoxygenation increased the expression of BRCA1 and
      BRCA2. CONCLUSION: Hypoxia is associated with radiation resistance. Therefore,
      reoxygenation may enhance the radiosensitivity of hypoxic cells. BRCA1 and BRCA2
      may be associated with factors for radiation resistance by regulation of cell
      cycle progression.

PMID- 21965749
TI  - Down-regulation of EGFL8: a novel biomarker for advanced gastric cancer.
AB  - BACKGROUND: Recently, we have reported an important role of epidermal growth
      factor-like domain 8 (EGFL8) in the progression of colorectal cancer (CRC) and
      documented EGFL8 to be a novel prognostic biomarker for this malignancy. However,
      the function of EGFL8 in the other human gastroenterological malignancies such as
      gastric cancer remains largely unknown. PATIENTS AND METHODS: EGFL8 expression in
      53 cases of gastric cancer and the corresponding normal tissues were determined
      by quantitative real-time PCR and the EGFL8 down-regulation score for each
      patient was calculated. Subsequently, the correlations between EGFL8 down
      regulation score and the clinicopathological features of gastric cancer were
      evaluated. RESULTS: EGFL8 expression was significantly lower in the gastric
      cancer tissues than the corresponding normal tissues (p=0.0001) and the down
      regulation of EGFL8 was evident in 73.6% (39/53) of the gastric carcinomas. More
      importantly, EGFL8 down-regulation was correlated significantly with peritoneal
      dissemination (p=0.037) and high TNM stage (p=0.025) of gastric cancer.
      CONCLUSION: The down-regulation of EGFL8 might be a novel biomarker for advanced
      gastric cancer.

PMID- 21965750
TI  - Increased soluble leptin receptor levels are associated with advanced tumor stage
      in colorectal cancer patients.
AB  - BACKGROUND: The leptin receptor is involved in modulating leptin activity, acting
      as a carrier protein. A link between leptin or leptin receptor and cancer
      development has been proposed and here, the hypothesis that leptin and its
      receptor might be implicated in colorectal cancer (CRC) progression and invasion
      was investigated. PATIENTS AND METHODS: A total of 71 consecutive patients with
      CRC were enrolled in the study. Serum leptin and leptin receptor levels were
      evaluated by commercial ELISA kits. RESULTS: The multinomial logistic regression
      model showed a positive association of leptin and leptin receptor with advanced
      tumor stages, which was significant for the leptin receptor in stage IV of
      disease. CONCLUSION: High circulating levels of leptin receptor occur in patients
      with advanced stage of colon cancer, suggesting a role for leptin in cancer
      progression and aggressiveness.

PMID- 21965751
TI  - Low-dose combinations of LBH589 and TRAIL can overcome TRAIL-resistance in colon
      cancer cell lines.
AB  - BACKGROUND: Despite the considerable advances in the treatment of colorectal
      cancer, substantial changes in treatment strategies are required to overcome the
      problems of drug resistance and toxicity. MATERIALS AND METHODS: Combinations of
      Pan-deacetylase inhibitor LBH589 and tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL) were studied in three colon cancer cell lines, HCT116,
      colo205, and HT29 (HCT116 and colo205 are TRAIL sensitive, whereas HT29 is TRAIL
      resistant). RESULTS: It was found that TRAIL-induced cytotoxicity was enhanced by
      LBH589 cotreatment in the TRAIL-sensitive cell lines, and in the TRAIL-resistant
      HT29 cell line. The cytotoxicity of low-dose TRAIL plus LBH589 was found to be
      comparable to that of high-dose TRAIL plus LBH589. Additionally, TRAIL and LBH589
      were significantly less toxic to normal UCB mononuclear cells than to the three
      colon cancer cell lines examined. CONCLUSION: LBH589 enhances TRAIL-induced
      apoptosis in human colon cancer cell lines, especially those resistant to TRAIL
      induced apoptosis.

PMID- 21965752
TI  - Thiamine supplementation attenuated hepatocellular carcinoma in the Atp7b mouse
      model of Wilson's disease.
AB  - BACKGROUND: Wilson's disease is caused by a genetic defect in P-type Cu(2+)
      ATPase (Atp7b), resulting in Cu(2+) accumulation in the liver, toxicity, and
      hepatocellular carcinoma. Exposure of HepG2 cells, and livers of Atp7b mutant
      mice to toxic Cu(2+) resulted in oxidation, (KGDH) and (PDH) enzyme inhibition,
      and death that was attenuated by thiamine. MATERIALS AND METHODS: The effect of
      oral thiamine supplementation (2%) on hepatocellular carcinoma induced by Cu(2+)
      accumulation in the livers of Atp7b animals at 4, 6, 9, 12, 16, and 21 months was
      demonstrated using gross morphology and multi-nucleate analysis. RESULTS: By 16
      months of age, untreated Atp7b animals became moribund, their livers were >180%
      the weight of controls and >75% of their liver was cancerous. At 16 months the
      livers of thiamine treated Atp7b mice were <130% the weight of controls and <30%
      cancerous, and at 21 months the mice were still active. However thiamine was
      ineffective in a subcutaneous xenograft model. CONCLUSION: This study suggests
      that thiamine may constitute a prophylactic for Wilson's disease-induced
      hepatocellular carcinoma.

PMID- 21965753
TI  - Effects of cytokinins, cytokinin ribosides and their analogs on the viability of
      normal and neoplastic human cells.
AB  - We examined the effects of some cytokinins and cytokinin ribosides including a
      series of adenosine analogs differently substituted in the N(6) position, along
      with some hypoxanthine derivatives on the viability of normal and neoplastic
      human cells. Cytokinins such as trans-zeatin, isopentenyladenine and
      benzyladenine do not show any effect, while cytokinin ribosides such as trans
      zeatin riboside, isopentenyladenosine, and benzylaminopurine riboside impair the
      viability of normal and neoplastic cells, apart from colon carcinoma LoVo cells.

PMID- 21965754
TI  - Antiproliferative effects of N-heterocyclic indolyl glyoxylamide derivatives on
      human lung cancer cells.
AB  - BACKGROUND: N-Heterocyclic indolyl glyoxylamide compounds are derived from the
      antimicrotubule agent D-24851, which exhibits anticancer activity after oral
      administration. The actions of these compounds on lung cancer cells are still
      unknown. Here, we investigated the effects of two N-heterocyclic indolyl
      glyoxylamides, BPR0C259 and BPR0C123, on non-small human lung cancer cells.
      MATERIALS AND METHODS: 3-[4,5-dimethylthiazol-2-yl]2,5-diphenyltetrazolium
      bromide (MTT) assay was used to determine the half maximal inhibitory
      concentration (IC(50)), cell viability and radiation response of A549 cells and
      H1299 cells. Apoptosis was determined by sub-G(1) ratio, colony formation assay
      and caspase-3 activation. Cell cycle distribution was detected using flow
      cytometry. RESULTS: Both compounds were able to inhibit the viability of human
      lung cancer cells, although the IC(50) of BPR0C123 was lower than that of
      BPR0C259. Both compounds induced significant sub-G1 and caspase-3 activation as
      low as 0.1 MUM in both cell lines. These effects were independent of p53
      activation because the level of serine-15 phosphorylated p53 was not affected
      after drug treatment. Furthermore, both compounds induced similar levels of
      G(2)/M phase arrest and radiosensitivity in these lung cancer cells. CONCLUSION:
      Current data suggest that N-heterocyclic indolyl glyoxylamides can suppress the
      proliferation of and potentially increase radiosensitivity of human lung cancer
      cells.

PMID- 21965755
TI  - Tumor endothelial marker 8 expression in triple-negative breast cancer.
AB  - BACKGROUND/AIM: Tumor endothelial marker 8 (TEM8) is a tumor endothelial
      associated antigen that is having an increasingly recognized role in tumor
      biology. The expression of TEM8 in triple-negative breast cancer (TNBC) has not
      yet been characterized. MATERIALS AND METHODS: We hypothesize that TEM8 is
      overexpressed in TNBC and in metastatic TNBC in lymph nodes (LN) compared to
      normal breast tissue and normal lymphatic tissue, respectively. We studied
      expression of TEM8 in cases of primary (n=17) and metastatic (n=2) TNBC using
      immunohistochemical analyses. RESULTS: All cases demonstrated increased
      expression of TEM8 in tumor tissue compared to non-cancerous breast tissue. TEM8
      was expressed at a higher level in the stroma adjacent to the TNBC in all cases,
      with focal immunoreactive areas within the tumor. TEM8 was not expressed in
      normal lymphoid tissue, but showed expression at sites of LN metastases.
      CONCLUSION: TEM8 would appear to represent a new biologic target for designing
      novel diagnostic or therapeutic approaches for TNBC.

PMID- 21965756
TI  - Clinical value of combined detection of serum matrix metalloproteinase-9,
      heparanase, and cathepsin for determining ovarian cancer invasion and metastasis.
AB  - AIM: This study evaluated the clinical value of the combined detection of serum
      cathepsin L (CL), heparanase (Hpa), and matrix metalloproteinase-9 (MMP-9) for
      determining the degree of ovarian cancer invasion and metastasis before surgery.
      PATIENTS AND METHODS: Enzyme-linked immunosorbent assays were used to measure the
      serum content of CL, Hpa, and MMP-9 in 217 patients with untreated ovarian cancer
      before surgery, 100 patients with benign ovarian tumors, and 101 healthy women as
      controls. In addition, the degrees of invasion and metastasis were assessed by
      the 'gold standard' of clinicopathological diagnosis. The associations of the
      preoperative serum CL, Hpa, and MMP-9 levels with the clinicopathological factors
      and metastatic status were analyzed. Receiver operating characteristic (ROC)
      curve analysis was used to evaluate the usefulness of these markers for
      determining the degree of ovarian cancer invasion before surgery. RESULTS: The
      serum CL, Hpa, and MMP-9 levels were significantly higher (p=0.001) in patients
      with malignant ovarian cancer compared with patients with benign ovarian tumors
      and healthy controls. The serum CL level was significantly higher in patients
      with epithelial ovarian carcinoma compared with non-epithelial ovarian carcinoma
      (p=0.048), whereas the serum levels of Hpa (p=0.109) and MMP-9 (p=0.544) did not
      differ significantly between these two groups. The serum CL, Hpa, and MMP-9
      levels correlated with the degree of differentiation and the FIGO staging
      (p>0.05). The serum CL (p=0.030) and MMP-9 (p=0.010) levels were significantly
      associated with peritoneal metastasis, and the serum Hpa level (p=0.042) was
      associated with distant metastasis. A ROC curve analysis revealed sensitivity of
      60.9%, 69.6%, and 72.2%, and specificity of 57.4%, 67.2%, and 68.9% for the
      preoperative serum levels of CL, Hpa, and MMP-9, respectively, as tumor markers
      for the degree of extra-pelvic metastasis. CONCLUSION: Elevated serum CL, Hpa,
      and MMP-9 levels are correlated with malignant invasion and progression in
      ovarian cancer. The combined detection of serum CL, Hpa, and MMP-9 may be useful
      for determining the extent of ovarian cancer metastasis before surgery.

PMID- 21965757
TI  - Case report of pneumatosis intestinalis secondary to sunitinib treatment for
      refractory gastrointestinal stromal tumor.
AB  - Pneumatosis intestinalis (PI) occurs when inter-luminal air enters the bowel wall
      of the gastrointestinal tract via a mucosal defect. The condition is caused by
      numerous disease states, direct trauma, and various drugs. When PI is secondary
      to drug therapy, discontinuation of the offending agent results in the resolution
      of PI. We report on the case of a 73-year-old male with a history of refractory
      gastrointestinal stromal tumor experiencing PI while on sunitinib treatment. PI
      was noted via computed tomography (CT) scans 68 days after starting sunitinib
      therapy and showed near complete resolution on a follow up CT performed one month
      after discontinuing sunitinib. Given that a CT scan performed five months prior
      to the initiation of sunitinib did not show PI, lack of abdominal symptoms in our
      patient, and resolution of PI after discontinuing sunitinib, the cause of PI in
      our patient was likely due to sunitinib treatment.

PMID- 21965758
TI  - Diagnostic value of 16 cellular tumor markers for metastatic thyroid cancer: an
      immunohistochemical study.
AB  - BACKGROUND: The prognosis for thyroid cancer differs between metastatic and non
      metastatic cases. To identify biomarkers useful for thyroid cancer diagnosis and
      to establish a marker panel for the early detection of metastatic thyroid
      carcinoma, this study compared histomorphological features and biomarker
      expression profiles in thyroid carcinomas according to pathological diagnoses.
      PATIENTS AND METHODS: Thyroid carcinoma samples were obtained from 113
      consecutive patients who underwent resection at multiple centers between 2001 and
      2008. These cases included 63 metastatic thyroid tumors (34 papillary carcinomas,
      20 follicular carcinomas, 9 undifferentiated carcinomas) and 50 non-metastatic
      thyroid tumors (36 papillary carcinomas, 14 follicular carcinomas). Tissue
      microarrays constructed using the 113 samples were analyzed by
      immunohistochemistry for the expression of 16 protein markers: MMP9, VEGF-C, E
      cadherin, MMP2, PPARgamma, PCNA, CXCR4, PTEN, C-myc, PTTG, HBME-1, p16, p53,
      FHIT, bFGF and hTERT. The clinicopathological variables with diagnostic
      significance were determined by multivariate analysis, and the predictive values
      of the identified biomarkers for metastasis in thyroid carcinoma were determined
      by receiver operating characteristic (ROC) curve analysis. RESULTS: The
      expression of six proteins, VEGF-C, MMP2, CXCR4, PTTG, HBME-1 and bFGF, was up
      regulated in metastatic compared to non-metastatic thyroid carcinoma. Multiple
      factor binary ordinal logistic regression analysis showed that MMP2, PTTG, VEGF
      C, CXCR4 and bFGF were independent factors associated with the metastatic status
      of thyroid carcinoma. ROC curve analysis of these five proteins revealed that
      VEGF-C and bFGF were the most useful protein markers for the diagnosis of
      metastatic thyroid cancer. CONCLUSION: MMP2, PTTG, VEGF-C, CXCR4 and bFGF are
      potential cellular tumor markers for identifying thyroid cancer with greater risk
      for metastasis and the novel combination of VEGF-C and bFGF as biomarkers may
      improve the accuracy of early detection and the differential diagnosis between
      metastatic and non-metastatic thyroid carcinoma.

PMID- 21965759
TI  - Conventional cytogenetics and breakpoint distribution by fluorescent in situ
      hybridization in patients with malignant hemopathies associated with
      inv(3)(q21;q26) and t(3;3)(q21;q26).
AB  - Inv(3)(q21q26)/t(3;3)(q21;q26) is recognized as a distinctive entity of acute
      myeloid leukemia (AML) with recurrent genetic abnormalities of prognostic
      significance. It occurs in 1-2.5% of AML and is also observed in myelodysplastic
      syndromes and in the blastic phase of chronic myeloid leukemia. The molecular
      consequence of the inv(3)/t(3;3) rearrangements is the juxtaposition of the
      ribophorin I (RPN1) gene (located in band 3q21) with the ecotropic viral
      integration site 1 (EVI1) gene (located in band 3q26.2). Following conventional
      cytogenetics to determine the karyotype, fluorescent in situ hybridization (FISH)
      with a panel of bacterial artificial chromosome clones was used to map the
      breakpoints involved in 15 inv(3)/t(3;3). Inv(3) or t(3;3) was the sole
      karyotypic anomaly in 6 patients, while additional abnormalities were identified
      in the remaining 9 patients, including 4 with monosomy of chromosome7 (-7) or a
      deletion of its long arm (7q-). Breakpoints in band 3q21 were distributed in a
      235 kb region centromeric to and including the RPN1 locus, while those in band
      3q26.2 were scattered in a 900 kb region located on each side of and including
      the EVI1 locus. In contrast to most of the inversions and translocations
      associated with AML that lead to fusion genes, inv(3)/t(3;3) does not generate a
      chimeric gene, but rather induces gene overexpression. The wide dispersion of the
      breakpoints in bands 3q21 and 3q26 and the heterogeneity of the genomic
      consequences could explain why the mechanisms leading to leukemogenesis are still
      poorly understood. Therefore, it is important to further characterize these
      chromosomal abnormalities by FISH.

PMID- 21965760
TI  - Phase II study of topotecan with cisplatin in Japanese patients with small cell
      lung cancer.
AB  - BACKGROUND: We conducted a phase II study of topotecan (Tp) with cisplatin (CDDP)
      in previously untreated Japanese patients with extensive-disease small cell lung
      cancer (ED-SCLC). PATIENTS AND METHODS: In stage 1, a total of 30 patients were
      allocated to Tp 0.65 mg/m(2) with CDDP 60 mg/m(2) day 1 or Tp 1.00 mg/m(2) with
      CDDP day 5 following prophylactic granulocyte colony stimulating factor (G-CSF)
      from day 6. In stage 2, the selective combination in 29 patients was evaluated
      for response rate, toxicity and overall survival. RESULTS: In stage 1, Tp 1.00
      mg/m(2) with CDDP day 5 was selected this schedule had a better hematological
      profile. In stage 2, the response rate was 83%, and grade 3/4 adverse events were
      hematological-toxicities. The median survival time was 17.5 months and the 1 year
      survival rate was 79%. CONCLUSION: Combination of Tp and CDDP on day 5 with G-CSF
      support is safe and effective for previously untreated ED-SCLC Japanese patients.

PMID- 21965761
TI  - Erlotinib in first-line therapy for non-small cell lung cancer: a prospective
      phase II study.
AB  - BACKGROUND: This phase II study evaluated efficacy of first-line erlotinib
      therapy for chemo-naive patients with non-small cell lung cancer (NSCLC) by their
      clinicopathological and/or molecular characteristics. PATIENTS AND METHODS:
      Eligible patients received erlotinib 150 mg daily until disease progression,
      followed by a gemcitabine/carboplatin doublet. By clinicopathological
      characteristics, the patients were categorized as squamous cell carcinoma (SQCC
      group), ever-smoker with adenocarcinoma (ever-smoking ADCC group), or never
      smoker with adenocarcinoma (never-smoking ADCC group). Epidermal Growth Factor
      Receptor (EGFR) mutations were prospectively assessed by a direct sequencing
      method and confirmed retrospectively by the Scorpion amplified refractory
      mutation system (ARMS). RESULTS: Seventy-five patients participated in this
      study. The direct sequencing method detected 18 EGFR mutations while ARMS
      detected an additional 3 EGFR mutations and 1 second EGFR T790M mutation. The
      objective response rates (ORR) were 71.7% in never-smoking ADCC, 25.0% in ever
      smoking ADCC, but no response in SQCC, while those of the patients with EGFR
      mutant and wild-type ere 85.7% and 10.0%, respectively. Even in never-smoking
      ADCC, the EGFR mutants responded better, with ORR of 88.9% and survived longer,
      with median survival time of 25.4 months, than those with wild-type EGFR with ORR
      of 25.0% and median survival time of 16.6 months (p<0.05). ORR for gemcitabine
      and carboplatin was 16.1%. CONCLUSION: The decision to administer first-line
      erlotinib should be decided by molecular characteristics, if known, but can be
      made by clinico-pathological characteristics as second best policy.

PMID- 21965762
TI  - Clinicopathological study of poorly differentiated colorectal adenocarcinomas:
      comparison between solid-type and non-solid-type adenocarcinomas.
AB  - AIM: We aimed to clarify the clinicopathological features of poorly
      differentiated colorectal adenocarcinomas and to define two subtypes of these
      adenocarcinomas. PATIENTS AND METHODS: We enrolled 78 patients, who had undergone
      surgery for poorly differentiated colorectal adenocarcinoma. On the basis of the
      microscopy results, the Por1 type is characterized by cancer cells with solid
      growth and little stroma; most cells contained round-shaped nuclei. The Por2 type
      is characterized by cancer cells with a predominantly trabecular structure; these
      tumors are rich in fibrous stroma. The two groups were compared for
      clinicopathological factors. RESULTS: The frequency of metastasis of the lymph
      node, liver, lung, and peritoneum in the Por2 group was significantly higher than
      that in the Por1 group. The survival rate in the Por2 group was lower than that
      in the Por1 group. CONCLUSION: The classification system described in this study
      is a simple and easy method for predicting poorly differentiated colorectal
      adenocarcinomas, and the prognosis of patients with Por2 tended to be unfavorable
      than that of Por1.

PMID- 21965763
TI  - Uterobrush method in the detection of endometrial pathology.
AB  - BACKGROUND: Endometrial brush cytology is a widely accepted method for the
      detection of endometrial lesions. The aim of this study was to evaluate the role
      of cytological sampling using Uterobrush in the screening of endometrial
      pathology. PATIENTS AND METHODS: This is a prospective double-blind study
      evaluating the efficacy of the Uterobrush method (Cooper Surgical, Trumbull, USA)
      in the detection of endometrial abnormalities. Endometrial cytology was performed
      during the period January 2009 to April 2010 in all symptomatic patients that
      underwent dilatation and curettage. The collected samples were firstly smeared
      directly onto a glassslide and consequently into Thin-Prep buffer. Cytologic
      features were evaluated according to the criteria of Tao. The main objective was
      to evaluate the efficacy of Uterobrush method comparing the results of cytologic
      and histopathologic examination. RESULTS: The sample of the study consisted of
      100 women aged 55.8 years (range 38-78 years) with recorded data regarding
      Uterobrush test and classic histologic examination. Fifty-five patients were
      postmenopausal. A total of 92% of the samplings were performed by trainees.
      Endometrial carcinoma was cytologically diagnosed in 8/9 patients, whereas
      endometrial polyps were diagnosed in 5/34 patients (14.7%). All the patients with
      simple hyperplasia were correctly diagnosed with the Uterobrush method, whereas
      the diagnosis of complex hyperplasia with or without atypia was correct in 85.7%
      and 100% of patients, respectively. Regarding endometrial carcinoma, the
      sensitivity, specificity, positive and negative predictive values were 88.9%,
      100%, 100% and 98.9%, respectively. On the other hand, regarding endometrial
      polyps, the sensitivity, specificity, positive and negative predictive values
      were 14.7%, 100%, 100% and 69.5%, respectively. CONCLUSION: Uterobrush is a
      reliable direct intrauterine sampling for detecting endometrial abnormalities
      especially endometrial carcinoma and hyperplasia, but not endometrial polyps. It
      is a well-tolerated, easy to use method, which provides generous endometrial
      sampling without contamination from the endocervix or the vagina.

PMID- 21965764
TI  - Expression status of ribonucleotide reductase small subunits hRRM2/p53R2 as
      prognostic biomarkers in stage I and II non-small cell lung cancer.
AB  - Overexpression of ribonucleotide reductase M2 (hRRM2) and p53-dependent RR small
      subunit (p53R2) has been correlated with tumor malignancy and progression in
      several types of cancer. The aim of this study was to determine the association
      of p53R2/hRRM2 expression with clinicopathological characteristics of stage I and
      II non-small cell lung cancer (NSCLC). Immunohistochemistry was conducted on a
      tissue array that included 92 samples. Correlations between hRRM2 and p53R2
      expression and clinicopathological factors, recurrence/metastasis, and outcomes
      were analyzed. The analyses revealed that there was no correlation between p53R2
      expression and clinicopathological factors; hRRM2 was only positively related to
      poor tumor differentiation (p=0.006). Regarding overall survival during the
      follow-up period, patients with p53R2+/hRRM2- tumors had the best outcomes
      (p<0.01). Multivariant Cox analysis revealed that p53R2 (risk=0.232, 95% CI=0.086
      0.626, p=0.004) not only served as a prognostic biomarker to predict survival,
      but also as an independent biomarker to predict disease-free survival
      (risk=0.545, 95% CI=0.301-0.987, p=0.045) of patients with NSCLC. Therefore, we
      consider that the expression of p53R2 can be used not only as a biomarker for
      overall survival, but also as an indicator for tumor recurrence. Based on our
      finding, p53R2 expression seems more important than that of hRRM2 in prognosis of
      early-stage lung cancer.

PMID- 21965765
TI  - Patterns of failures in endometrial cancer: clinicopathological variables
      predictive of the risk of local, distant and retroperitoneal failure.
AB  - The aim of this study was to assess the pattern of failure and the outcome of
      endometrial cancer patients and to analyze the variables predictive of the risk
      of local, distant and retroperitoneal lymph node disease recurrence. PATIENTS AND
      METHODS: The authors assessed 511 patients who underwent primary surgery. The
      median follow-up of survivors was 74 months. Peritoneal, hematogenous and lymph
      node recurrences outside retroperitoneal area were considered as distant
      failures. RESULTS: Tumor relapsed in 83 (16.2%) patients. Median time to
      recurrence was 18.5 months (range, 3-129 months). The relapse was local in 13
      cases, distant in 37, retroperitoneal in 22, and involved both distant and other
      sites in 11. Logistic regression showed that cervical involvement was the only
      independent predictor of local recurrence. Tumor grade, lymph-vascular space
      involvement (LVSI) and myometrial invasion were independent predictors of distant
      failure. Lymph node status and tumor grade were independent predictors of
      retroperitoneal recurrence. Five- and 10-year overall survival rates were 87.1%
      and 79.5%, respectively. Patient age, lymph node status, cervical involvement,
      tumor grade, LVSI and myometrial invasion were independent prognostic variables
      for overall survival. CONCLUSION: Cervical involvement was an independent
      predictor of local recurrence, LVSI and myometrial invasion were independent
      predictors of distant failure, lymph node status was an independent predictor of
      retroperitoneal relapse, and tumor grade was an independent predictor of both
      distant and retroperitoneal recurrence. The identification of risk factors for
      different patterns of failure can be useful in better tailoring adjuvant
      treatment.

PMID- 21965766
TI  - No detection of BK virus, JC virus, KI, WU and Merkel cell polyomaviruses in
      cerebrospinal fluid of patients with neurological complications after
      hematopoetic stem cell transplantation.
AB  - Neurological complications, often due to viral reactivation, after allogeneic
      hematopoetic stem cell transplantation (HSCT) are associated with increased
      mortality. Here, cerebrospinal fluid from 20 HSCT patients with neurological
      symptoms were analyzed and found to be negative by PCR for BK virus, JC virus,
      KI, WU and Merkel cell polyomavirus DNA.

PMID- 21965767
TI  - Oxaliplatin scale and National Cancer Institute-Common Toxicity Criteria in the
      assessment of chemotherapy-induced peripheral neuropathy.
AB  - AIM: The aim of the study was to compare two different neurotoxicity scales in
      grading chemotherapy-induced neurotoxicity. PATIENTS AND METHODS: The study
      sample consisted of 114 cancer patients who started chemotherapy with vinca
      alcaloids, platinum derivatives or taxanes. Neurotoxicity was evaluated with the
      National Cancer Institute-Common Toxicity Criteria (NCI-CTC) and oxaliplatin
      scales at baseline and after every third chemotherapy cycle thereafter. RESULTS:
      Neuropathy was detected in 60%, 55% and 75% at the second, third and fourth
      visits, respectively, with the NCI-CTC sensory scale and 59%, 55% and 80% with
      the oxalipalatin scale. Of the patients with grade 3-4 toxicity on the
      oxaliplatin scale, 23/53 had grade 1, 18/53 had grade 2 and 12/53 had grade 3
      neurotoxicity on the NCI-CTC sensory scale. CONCLUSION: The oxaliplatin and NCI
      CTC sensory scales were comparable in identifying chemotherapy-induced
      neuropathy, but the oxaliplatin scale more often detected the progression of the
      symptoms.

PMID- 21965768
TI  - Bowel complication during robotic-assisted laparoscopic radical prostatectomy.
AB  - BACKGROUND: Bowel injury is a devastating complication of radical prostatectomy.
      The incidence and management of bowel injury occurring during robot-assisted
      laparoscopic radical prostatectomy (RALP) performed at our institution was
      reviewed. PATIENTS AND METHODS: Only three (1.04%) out of 288 RALPs performed at
      our institution between December 2005 and May 2011 were complicated by bowel
      injury. The mean patient age was 71 years (range 67 to 79) and mean prostate
      specific antigen was 19.6 ng/ml (range 6.4 to 30.6). All three patients had
      received transurethral resection of prostate (TURP) before RALP. Clinical stages
      were T1b, T1c, T2c, respectively. The mean preoperative Gleason score was 6.7
      (range 6 to 7). The mean operative time was 201 minutes (range 170 to 240).
      RESULTS: Two of the intraoperative injuries were diagnosed and repaired
      intraoperatively and one was diagnosed postoperatively. In the two cases of
      intraoperative diagnosis and repair, one patient healed primarily without
      colostomy and a recto-urinary fistula was evidenced by pneumaturia in the other.
      That patient underwent a failed fistula repair and required colostomy. The
      patient with unrecognized bowel injury presented with atypical acute abdomen and
      required laparotomy and colostomy. No perioperative mortality occurred in these
      three cases. CONCLUSION: Bowel injury during RALP can be managed
      intraoperatively; unrecognized bowel injury may present with atypical acute
      abdomen and dissemination of the presentation and management of bowel injury, and
      modifications to avoid complications might help to produce improved outcomes in
      RALP.

PMID- 21965769
TI  - The prognostic role of lymphovascular invasion in urothelial-cell carcinoma of
      upper and lower urinary tract.
AB  - BACKGROUND: Carcinoma of the bladder represents the fourth most common cancer in
      men and the eighth most common malignancy in women in Europe and the United
      States. Prognostic factors for recurrence and survival are tumor stage and
      dimension, tumor grade and the presence of lymph node metastasis. We assess the
      impact and the role of lymphovascular invasion (LVI) on the prognosis of patients
      treated for lower and upper tract urothelial carcinoma by reviewing the
      literature curentable. MATERIALS AND METHODS: We performed a detailed review of
      the literature to assess the prognostic role of LVI assessed in histological
      specimens of urothelial cell carcinoma of the upper and lower urinary tract.
      RESULTS: We presented the definition of lymphovascular invasion in histological
      specimens of urothelial carcinoma. LVI in histological specimens was correlated
      significantly with increasing tumor stage and grade. Moreover, LVI is
      significantly correlated with earlier disease recurrence and a lower cancer
      specific survival, and seems to be an independent predictor of recurrence-free
      survival on multivariate Cox analysis. CONCLUSION: LVI in histological specimens
      seems to have an important prognostic value for patients with urothelial cell
      carcinoma of the upper and lower urinary tract, and could be a useful tool for
      the urologist in choosing the best and most appropriate management during disease
      treatment and follow-up.

PMID- 21965770
TI  - Sunitinib re-challenge in metastatic renal cell carcinoma treated sequentially
      with tyrosine kinase inhibitors and everolimus.
AB  - Therapy of patients with metastatic renal cell carcinoma (mRCC) requires
      sequential use of several agents with different mechanisms and minimal cross
      resistance between the different agents. Tyrosine kinase inhibitors (TKIs) and
      mammalian target of rapamycin (mTOR) inhibitors prolong progression-free survival
      (PFS) in patients with mRCC. Re-challenge with TKIs provides clinical benefit
      after everolimus in patients with mRCC. We report the case of an mRCC patient
      with lung and bone metastases, treated sequentially with sunitinib, sorafenib and
      everolimus. The patient had an objective response in reducing bone metastases,
      but adaptative and concomitant progression in lung metastases during sunitinib re
      challenge. Previously, these lung metastases had responded to sunitinib. This
      intriguing paradox suggests that not only was sunitinib able to target a specific
      metastatic site during the re-challenge, as seen by the reduction of bone
      metastases, but it also elicited a more invasive adaptation and progression of
      lung tumor cells.

PMID- 21965771
TI  - Significant association of caveolin-1 (CAV1) genotypes with breast cancer in
      Taiwan.
AB  - AIM: Japanese and American groups reported that single nucleotide variation of
      caveolin-1 gene (CAV1) plays an important role in breast cancer risk. The aim of
      this study was to evaluate the association of six polymorphic genotypes of CAV1,
      which is reported to be overexpressed in tumors, with breast cancer within a
      Taiwanese population. PATIENTS AND METHODS: A total of 1232 patients with breast
      cancer and equal number of healthy controls in central Taiwan were genotyped via
      polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP)
      and six polymorphic variants of CAV1 were analyzed for their association with
      breast cancer susceptibility. RESULTS: The distribution of genotypes of CAV1
      G14713A and T29107A were significantly different between breast cancer and
      control groups (p=5.6*10(-5) and 1.9*10(-4), respectively), while those for CAV1
      C239A, G21985A, T28608A and G32124A were not significant (p>0.05). The
      percentages of AG genotype of G14713A and TT genotype of T29107A are higher in
      the cancer group than in the control group. The two single nucleotide
      polymorphisms were chosen for haplotype analysis and the data showed that
      compared with GG/TT haplotype of CAV1 G14713A/T29107A, the GG/AT and GG/AA groups
      have a lower risk of breast cancer (odds ratio, OR=0.69, 95% confidence interval,
      CI=0.57-0.92). On the contrary, the AG/TT haplotype confers a higher risk of
      breast cancer (OR=1.50, 95% CI=1.14-2.12). CONCLUSION: Our results provide
      evidence for CAV1 genotypes being involved in predisposition to breast cancer.
      The association of the potential risk haplotype agrees well with a role of CAV1
      genotype in breast cancer risk and the association with tumor progression needs
      further investigation.

PMID- 21965772
TI  - Endoscopic appearance and clinicopathological character of breast cancer.
AB  - BACKGROUND: The Japanese Association of Mammary Ductoscopy proposed a
      classification system based on the objective endoscopic appearance of intraductal
      lesions. This system includes four categories: solitary polypoid, multiple
      polypoid, superficial, and combined type. However, previous studies did not
      adequately compare endoscopic findings with histological findings and the
      prognosis. PATIENTS AND METHODS: One hundred and ten patients with nipple
      discharge who had intraductal tumors were identified by mammary ductoscopy, and
      25 breast cancer patients were identified from our database of records between
      2001 and 2008. The clinicopathological data and outcomes of these patients were
      then reviewed. RESULTS: Lesions in 25 breast cancer patients comprised 12
      polypoid solitary type, 3 polypoid multiple type, 5 superficial type, and 5
      combined type. Polypoid type showed a low sensitivity on cytological analysis (5
      malignant and 10 benign). On the contrary, superficial or combined type showed a
      high sensitivity (4 malignant and 1 benign). Furthermore, invasive ductal
      carcinoma was frequently found in the solitary polypoid type. Actuarial disease
      free survival for all patients at 10 years was 78%. The estrogen/progesterone
      receptor status and endoscopic appearance did not significantly affect disease
      free survival (DFS), while there was a significant difference in DFS between
      ductal carcinoma in situ and invasive ductal carcinoma. CONCLUSION: Ductoscopy is
      a useful procedure for guiding subsequent breast surgery in the treatment of
      nipple discharge, and the appearance may be essential in treating breast cancer
      patients with nipple discharge.

PMID- 21965773
TI  - Expression of thymidylate synthase and dihydropyrimidine dehydrogenase in primary
      oral squamous cell carcinoma and corresponding metastases in cervical lymph
      nodes: association with the metastasis suppressor CD82.
AB  - Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are 5
      fluorouracil (5-FU) metabolizing enzymes and are involved in the sensitivity of
      carcinoma patients to 5-FU. Although 5-FU is often used for the treatment of oral
      carcinoma, there has not been any investigation into the expression of these
      enzymes in metastatic lymph nodes or of their roles in the effectiveness of 5-FU
      in treating lymph node-metastatic cancer. Oral squamous cell carcinoma (OSCC)
      often metastasizes to the lymph nodes, and these enzymes may be significant in
      the survival of patients with this disease. This study investigated the
      expression of TS and DPD in cervical lymph node metastases and its relationship
      with primary OSCC, as well as the interaction between these enzymes and Kangai
      1(KAI1/CD82) which is a metastasis suppressor protein. Surgical specimens from 20
      cases of OSCC with lymph node metastasis, 20 cases of OSCC without lymph node
      metastasis, and 10 cases of normal mucosa were examined by immunohistochemistry.
      The relationship between TS and DPD expression and clinicopathological data was
      analyzed. TS and DPD proteins were overexpressed in primary OSCC compared to that
      in normal mucosa. TS expression of the primary oral cancer cells in the group
      with lymph node metastasis was higher than that of those without. DPD expression
      did not significantly correlate with the occurrence of lymph node metastasis, nor
      was it different between primary oral cancer cells and cervical metastases. CD82
      expression was significantly reduced in lymph node metastases. These findings
      indicate that TS and CD82 may be of great value in assessing lymph node
      metastasis of OSCC, and could be taken as new targets for therapy of metastatic
      OSCC.

PMID- 21965774
TI  - Severe late complications in patients with uterine cancer treated with
      postoperative radiotherapy.
AB  - AIM: Severe late complications, particularly radiation enterocolitis and leg
      edema, remain major problems in patients with uterine cancer, who have undergone
      hysterectomy and postoperative external beam radiotherapy (EBRT). We carried out
      this retrospective analysis to identify the incidence of risk factors for such
      complications. PATIENTS AND METHODS: The records of 228 patients, who underwent
      radical hysterectomy and postoperative EBRT (uterine cervix: 149 patients;
      uterine corpus: 79 patients) were reviewed retrospectively. The majority of the
      patients (90.8%) were treated with 50 to 50.4 Gy EBRT in conventional
      fractionations with anteroposterior fields. Intracavitary brachytherapy (ICBT)
      was administered to 9 patients (3.9%), and 35 patients (15.2%) received
      chemotherapy. The median follow-up for all 228 patients was 81.7 months (range, 1
      273 months). RESULTS: Nineteen patients (8.3%) developed severe radiation
      enterocolitis with a median latency of 12.6 months, and the ileum was the most
      frequently affected site. On multivariate analysis, smoking was an independent
      predictor of severe radiation enterocolitis. Nineteen patients (8.3%) developed
      severe leg edema with a median latency of 32.7 months. The degree of leg edema
      did not improve in any of the 19 patients despite intensive treatment. On
      multivariate analysis, addition of ICBT was an independent predictor of severe
      leg edema. CONCLUSION: Severe radiation enterocolitis and severe leg edema were
      each observed in approximately 8% of patients with uterine cancer, who underwent
      postoperative radiotherapy. Severe radiation enterocolitis correlated strongly
      with smoking, and severe leg edema correlated strongly with addition of ICBT.
      These factors should be considered before administering postoperative
      radiotherapy to uterine cancer patients.

PMID- 21965775
TI  - Docetaxel plus 5-fluorouracil and cisplatin (DCF) induction chemotherapy for
      locally advanced borderline-resectable T4 esophageal cancer.
AB  - BACKGROUND: This study aimed to evaluate the efficacy of docetaxel plus 5
      fluorouracil and cisplatin (DCF) induction chemotherapy for locally advanced
      borderline-resectable T4 esophageal cancer. PATIENTS AND METHODS: We
      retrospectively analyzed data regarding thirty patients with borderline
      resectable T4 tumor who received either DCF or cisplatin plus 5-fluorouracil (FP)
      as induction chemotherapy. RESULTS: The overall response rate was significantly
      better for the DCF group than the FP group. In the DCF group, 6/16 patients
      achieved a grade 2 histological post-chemotherapeutic effect after treatment,
      compared to 1/14 in FP group. Except for myelotoxicity, no other significant
      differences in toxicity were observed during induction chemotherapy between
      groups. The DCF regimen did not result in increased postoperative complications
      compared to the FP regimen. Postoperative recurrence or distant metastasis was
      observed in 7/10 of FP patients and 5/12 of DCF patients. CONCLUSION: DCF
      induction chemotherapy may be an option for conversion therapy of initially
      unresectable, locally advanced esophageal cancer.

PMID- 21965776
TI  - The role of chemotherapy in metastatic gastric cancer.
AB  - In the setting of metastatic or inoperable gastric cancer, the current evidence
      shows that chemotherapy improves survival in comparison to best supportive care
      and that combination chemotherapy is superior to monotherapy in terms of
      survival, response rate and symptom control. Many randomized phase III trials
      tested different combinations of therapies showing better outcome for cisplatin
      containing schedules. In recent years, new drugs, such as docetaxel, oxaliplatin,
      irinotecan, capecitabine and S1 have also been tested in phase III studies.
      Unfortunately, in all of these studies, but one, the median survival remained
      below one year. Although there are no internationally accepted standard regimens,
      in Europe, ECF (epirubicin, cisplatin, fluorouracil) has been considered the
      reference regimen; in the US cisplatin-fluoropyrimidine combinations are mainly
      used, while in Japan, cisplatin with S1 has become the standard. Currently,
      various targeted agents are being tested in clinical trials and promising data
      have been recently published for trastuzumab-containing therapy, with median
      survival exceeding one year. As regards progressive disease, about 20%-50% of
      patients receive second line chemotherapy and, although two phase III studies
      reported survival benefit with single-agent chemotherapy, the role of
      chemotherapy in this setting still needs to be defined. Despite the progress of
      recent decades, metastatic gastric cancer remains an incurable disease, and
      treatment options should primarily take into account the quality of life and
      quality-adjusted survival of patients. The hope for the future is that tailored
      interventions based on new cytotoxic drugs, targeted therapies and integration of
      molecular determinants may help to improve the current treatments.

PMID- 21965777
TI  - Hypofractionated radiotherapy with or without IGRT in prostate cancer:
      preliminary report of acute toxicity.
AB  - BACKGROUND: To evaluate the acute tolerance to hypofractionated schedule of
      patients with prostate cancer. PATIENTS AND METHODS: We treated 62 patients with
      intermediate risk prostate cancer. All patients were treated with a total dose of
      43.8 Gy on seminal vesicles and 54.75 Gy on prostate, 3.65 Gy per fraction, three
      times a week for a total of 5 weeks. All patients underwent neoadjuvant,
      concomitant and adjuvant hormonal therapy. Thirty-six patients were submitted to
      image-guided radiation therapy (IGRT). RESULTS: Median follow-up was 15 months
      (range 3-33 months). Toxicities during the treatment were: grade 1-2
      gastrointestinal (GI) toxicity, 22.6%; grade 1-2 genitourinary (GU) toxicity,
      51.6%. Toxicities 3 months after the end of the treatment were grade 1-2 GI 6.5%,
      grade 1-2 GU 9.7%. No statistical difference was observed comparing acute
      toxicity in patients treated with or without IGRT. CONCLUSION: This study showed
      that the hypofractionation schedule used is well tolerated, with a low rate of
      acute grade 1-2 GI toxicity and without major grade (>=3) acute toxicity. Longer
      follow-up is needed to determine if this low rate of acute toxicity will be
      translated in a low rate of late toxicity.

PMID- 21965778
TI  - Changes in serial magnetic resonance spectroscopy predict outcome in high-grade
      glioma during and after postoperative radiotherapy.
AB  - AIM: To determine any correlation between magnetic resonance spectroscopy (MRS)
      pattern of high-grade glioma before, during, and after radiotherapy (RT) with
      overall survival (OS) and progression-free survival (PFS). PATIENTS AND METHODS:
      Twenty-six patients prospectively underwent surgery and RT to 60 Gy. MRS was
      performed before RT, at week 4 of RT, and 2 months post-RT. Normalized and
      relative metabolite ratios were evaluated. Patients were grouped according to
      similar evolving MRS patterns and analyzed for differences in OS and PFS.
      RESULTS: Significant decreases in tumor choline/N-acetyl-aspartate and normalized
      choline were observed from baseline to post-RT. After a median follow-up of 22.9
      months, patients with >40% decrease in normalized choline from week 4 during RT
      to 2 months post-RT had a significantly worse median OS (9.1 months vs. not
      reached, p<0.00001) and PFS (5.8 vs. 19.8 months, p=0.0018). CONCLUSION: The
      change in normalized choline at 2 months post-RT was highly prognostic for PFS
      and OS. This may allow more individualized response-based treatment.

PMID- 21965779
TI  - Efficacy of meloxicam in combination with preoperative chemotherapy for breast
      cancer - Japan Breast Cancer Research Network (JBCRN) 02-1 trial.
AB  - BACKGROUND: We reported that doxorubicin and cyclophosphamide (DC) followed by
      weekly paclitaxel is an active and manageable preoperative regimen for breast
      cancer patients. However, as one of the side effects of paclitaxel, neuropathy
      was noted in up to 30% of patients. Cyclooxygenase-2 (COX-2) and its derived
      prostaglandins play a role in stimulating angiogenesis, inhibiting apoptosis, and
      suppressing the immune response. Some recent studies showed that COX-2
      inhibitors, such as meloxicam, have the potential to enhance tumor suppression
      and reduce the severity of paclitaxel-induced neuropathy. PATIENTS AND METHODS:
      Four cycles of DC (doxorubicin: 60 mg/m(2) and cyclophosphamide: 600 mg/m(2))
      administered intravenously (i.v.) on day 1 every 21 days were followed by 12
      cycles of paclitaxel i.v. (80 mg/m(2)) every 7 days, prior to surgery. During
      paclitaxel therapy, breast cancer patients were administered meloxicam (10 mg per
      day) daily, when experiencing symptoms of grade 2 neuropathy (motor or sensory).
      The primary endpoint was the pCR rate achieved with the treatment. RESULTS: Forty
      three patients received preoperative chemotherapy between April 2004 and March
      2007 at six centers. The patient population was identified from a database of the
      Japan Breast Cancer Research Network. Clinical responses were rated as clinically
      complete response (cCR) in 9 patients (22%), clinically partial response (cPR) in
      25 patients (59%), and clinically stable disease (cSD) in 9 patients (19%). pCR
      was seen in 25.6%. In addition, we identified 15 patients, who developed grade 2
      neuropathy during paclitaxel therapy and subsequently received meloxicam.
      Meloxicam application had a marked effect within 28 days of initiation. The
      sensory neuropathy of the patients was reduced gradually, but their motor
      neuropathy did not improve. Five out of the 15 patients with neuropathy
      experienced symptom improvement after meloxicam treatment (p<0.05; before versus
      after 2 months of meloxicam administration). Furthermore, among the 15 patients,
      who received meloxicam, clinical responses were rated as cCR in 2 patients, cPR
      in 4 patients, and cSD in 9 patients. The pCR was seen in 4 patients (26.7%).
      CONCLUSION: Although meloxicam in combination with DC and weekly paclitaxel
      chemotherapy did not show promising therapeutic activity, it may provide some
      relief for neuropathy.

PMID- 21965780
TI  - Metabolic activation of irinotecan during intra-arterial chemotherapy of
      metastatic colorectal cancer.
AB  - Biotransformation of irinotecan (CPT-11) into its pharmacologic active metabolite
      SN-38 was investigated in patients treated for advanced colorectal cancer. A dose
      of 180 mg/m(2) CPT-11 was administered to 6 patients by 60 min hepatic intra
      arterial infusion (HAI) via a surgically implanted Port-a-Cath(r) system. Blood
      samples were collected from 0 to 360 min after start of HAI, and CPT-11 plus
      metabolites were analysed by a selective reversed phase HPLC method. The
      objective of this study was to evaluate the extent to which SN-38 is generated
      after HAI of irinotecan given at a low dose of 180 mg/m(2). In a second
      investigation, CPT-11 was administered via conventional intravenous infusion
      (dose 180 mg/m(2), 60 min infusion time, 11 patients) and CPT-11 plus metabolites
      were quantified using identical analytical procedure. Compared to i.v. infusion,
      the pharmacokinetics of CPT-11 and SN-38 were altered by HAI. The mean c(max) of
      CPT-11 after HAI was reduced by 37%, whereas the mean c(max) of SN-38 increased
      by 60%. HAI resulted in a desired, increased metabolic conversion of CPT-11 into
      SN-38 and might improve the regional availability of the pharmacologic active
      metabolite SN-38 at the site of tumor. Plasma concentrations of the metabolites
      SN-38 glucuronide and APC remained unaffected by the route of administration.

PMID- 21965781
TI  - Long-term disease-free survival following dendritic cell therapy and resection of
      small bowel melanoma metastases - a case report.
AB  - BACKGROUND: Although the resection of solitary visceral melanoma metastases is
      indicated when possible, further progression of metastatic disease is seen in the
      vast majority of patients. New modalities of immunotherapy can offer durable
      disease control in a significant proportion of melanoma patients. CASE REPORT: A
      28-year-old man was diagnosed with stage III melanoma in 2003 and was treated
      with autologous dendritic cells in the adjuvant setting. Five years later
      melanoma metastases causing small bowel obstruction were surgically removed and
      he was retreated with dendritic cells. Following 5 months without disease
      manifestations, the patient presented with intermittent abdominal discomfort.
      Following the visualization of a hot spot at the level of the jejunum on 18F
      fluorodeoxyglucose position-emission tomography, the patient underwent a
      laparotomy, during which a solitary melanoma metastasis of the small bowel
      causing intussusception was resected. The patient has so far remained disease
      free, more than one year after the latest surgical intervention. CONCLUSION:
      Combined modality treatment with surgery and immunotherapy may result in an
      improved long-term outcome for patients with metastatic melanoma.

PMID- 21965782
TI  - Immunohistochemical expression and prognostic significance of CCND3, MCM2 and
      MCM7 in Hodgkin lymhoma.
AB  - BACKGROUND: Increased proliferation rate may be associated with inferior outcome
      in patients with Hodgkin lymphoma (HL). Minichromosome maintenance proteins
      (MCMs) and D-type cyclins are essential for DNA replication. PATIENTS AND
      METHODS: Lymph node sections from 138 HL patients were immunohistochemically
      stained for cyclin D3 (CCND3), MCM2 and MCM7 aiming to investigate clinical
      outcome. RESULTS: Higher MCM2 expression was observed in patients in early stage
      disease and normal albumin levels; higher MCM7 was found for asymptomatic
      patients, early stage disease, <5 involved sites, no anemia and normal albumin
      levels; higher CCND3 expression was found for older patients and normal lactate
      dehydrogenase (LDH). Univariate analysis revealed no correlation with failure
      free (FFS) or overall survival (OS). Multivariate analysis revealed that high
      MCM7 expression was an adverse prognostic factor for OS, along with older age and
      advanced stage, while it was of borderline significance for FFS when adjusted for
      stage. CONCLUSION: These results suggest that MCM7 deserves further evaluation as
      a potential independent prognostic factor in larger patient series.

PMID- 21965783
TI  - Expression of zinc finger 23 gene in human hepatocellular carcinoma.
AB  - The aim of this study was to investigate the relationship between human zinc
      finger 23 (ZNF23) expression and clinico-pathological characteristics in patients
      suffering from hepatocellular carcinoma (HCC), and to investigate ZNF23
      expression in relation to cell apoptosis. PATIENTS AND METHODS: Thirty-seven HCC
      samples were collected and ZFP23 mRNA levels were determined by real-time reverse
      transcription-polymerase chain reaction (RT-PCR). Correlation between ZNF23
      expression and patients' clinical characteristics was analyzed. For determining
      the effect of ZNF23 on cell apoptosis, HepG2 cells were exposed to cisplatin at
      different concentrations and ZNF23 mRNA assayed. RESULTS: Median relative mRNA
      levels of ZNF23 mRNA in HCC tissues and adjacent tissues were 8.84 (3.59-15.05)
      and 22.20 (13.85-42.90), respectively (U=259.5, p<0.01). Median mRNA levels of
      ZNF23 in patients with Edmondson stage I+II disease [12.80 (4.80-19.50)] were
      much higher than those of patients with stage III+IV disease [5.01 (2.88-11.68),
      U=99.00, p<0.05]. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      assay demonstrated that cisplatin significantly inhibited cell proliferation of
      HepG2 cells in a dose-dependent manner, which was positively correlated to cell
      apoptosis (F=27.89, p<0.01), and in response to increasing cisplatin
      concentrations, ZNF23 mRNA levels increased in the cells. CONCLUSION: Cisplatin
      induced apoptotic effect in HepG2 cells may be mediated via the up-regulation of
      ZNF23, which suggests that the ZNF23 gene could play an important role in the
      development of hepatocellular carcinoma.

PMID- 21965784
TI  - Interaction of CCND1 genotype and smoking habit in Taiwan lung cancer patients.
AB  - AIM: Cyclin D1 (CCND1) is critical in the transition of the cell cycle from G1 to
      S phase and unbalanced cell cycle regulation is a hallmark of carcinogenesis. The
      study aimed at investigating the association of CCND1 genotypes with lung cancer
      risk in Taiwan and examining the interaction between CCND1 genotype and smoking
      habit. PATIENTS AND METHODS: CCND1 A870G (rs9344) and C1722G (rs678653) genotypes
      were determined by polymerase chain reaction (PCR) and restriction fragment
      length polymorphism (RFLP) analysis of DNA from the blood of 358 lung cancer
      patients and 716 cancer-free healthy controls. RESULTS: The results showed that
      there were significant differences between lung cancer and control groups in the
      distribution of the genotypes (p=0.0003) and allelic frequency (p=0.0007) in the
      CCND1 rs9344 genotype. Individuals who carried AG or GG genotype had 0.59- and
      0.52-fold risk, respectively, of developing lung cancer compared to those who
      carried the AA genotype (95% CI=0.44-0.78 and 0.35-0.79, respectively). There was
      also an obvious interaction of CCND1 rs9344 genotype with personal smoking habit
      on lung cancer risk (p=0.0009). CONCLUSION: These findings support the conclusion
      that cell cycle regulation may play a role in lung cancer development and that
      CCND1 rs9344 polymorphism together with smoking habit maybe a useful biomarker
      for lung cancer prediction.

PMID- 21965785
TI  - Identification of the distinctive type i/XhoI+ strain of Epstein-Barr virus in
      gastric carcinoma in Peru.
AB  - AIM: To clarify the reason for the low frequency of Epstein-Barr virus-associated
      gastric carcinoma (EBVaGC) in Peru, despite the high frequency reported in
      neighboring countries, the distribution of the distinctive EBV (type i/XhoI+)
      strain in EBVaGC and a healthy population was examined. MATERIALS AND METHODS:
      EBV polymorphisms in BamHI W1/I1 and XhoI restriction site of the latent membrane
      protein 1 gene (LMP1) were examined among 11 EBVaGCs and 172 healthy controls
      from Peru, and these frequencies were compared with those in a previous study of
      Chile and Colombia (n=303). RESULTS: The frequency of the distinctive EBV strain
      in EBVaGCs (55%) was significantly higher than that in controls (7%).
      Furthermore, the frequency of this EBV type in Peruvian controls was
      significantly lower than that in controls from Chile and Colombia (27%, p<0.001).
      CONCLUSION: The low frequency of the distinctive EBV strain among the Peruvian
      population might be a reason for the lower incidence of EBVaGC in Peru, as
      compared with neighboring countries.

PMID- 21965786
TI  - Lower serum total testosterone is associated with lymph node metastases in a
      radical prostatectomy cohort study.
AB  - BACKGROUND: Data on testosterone levels of patients with prostate cancer of
      different grade and stage are inconsistent. We retrospectively investigated serum
      total testosterone of a radical prostatectomy cohort to further shed light on
      this problem. PATIENTS AND METHODS: The preoperative level of serum total
      testosterone of 217 patients (mean age: 65+/-5.8 years) undergoing radical
      prostatectomy between 1989 and 2002 was analyzed for possible associations with
      Gleason score (<=6 vs. <7 vs. 8-10) and tumor stage (pT2 vs. pT3 vs. N+) with
      adjustment for age, diabetes and obesity. Patients exhibiting prostate-specific
      antigen (PSA) levels of >10 ng/ml and biopsy Gleason scores of >=7 were submitted
      to standard lymphadenectomy. RESULTS: The multivariate model revealed a
      significant effect of body mass index (BMI) (p=0.0003) and diabetes (p=0.002) on
      testosterone levels. Significantly lower testosterone levels were recorded in
      patients with nodal metastases (p<0.0001) compared to patients with non
      metastatic disease. No significant associations between testosterone, Gleason
      score and stage were found in patients with non- metastatic disease. CONCLUSION:
      Testosterone levels prior to radical prostatectomy were lower in patients with
      nodal involvement.

PMID- 21965787
TI  - Vitamin D in colorectal, breast, prostate and lung cancer: a pilot study.
AB  - BACKGROUND: Many studies have demonstrated the relationship between vitamin D and
      cancer of many different sites, including of the breast, colorectum, prostate and
      lung. Most epidemiological studies have assessed the effects of dietary intake
      only, although endogenous production after sun exposure is the main source of
      vitamin D. The aim of our pilot study was to study serum levels of vitamin D in
      general population and in patients with different type of cancer. PATIENTS AND
      METHODS: The control group consisted of 214 healthy individuals. Pathological
      groups of patients included 170 patients with different cancer types (28 patients
      with prostate cancer, 43 patients with breast cancer, 49 patients with colorectal
      cancer and 50 patients with lung cancer). All of the patients were enrolled in
      the early clinical stage of cancer up to clinical stage III. Advanced stages were
      not included into the study. Vitamin D serum levels were measured using ECLIA
      Roche method. RESULTS: All the results for serum vitamin D from pathological
      groups were significantly lower compared to the levels of the control group. All
      the cancer types had a high incidence rate of very low serum levels of vitamin D.
      Lung cancer had the highest incidence rate of very low vitamin D serum levels.
      CONCLUSION: We found a high incidence of hypovitaminosis D in cancer patients
      compared to a healthy control group among a Czech population. This incidence rate
      is higher in comparison to data found in literature from the other parts of the
      world. Based on the data from this study, a large epidemiological study
      monitoring vitamin D serum levels in the healthy population and in cancer
      patients in the Czech Republic has been already proposed.

PMID- 21965788
TI  - Effect of ibandronate on disseminated tumor cells in the bone marrow of patients
      with primary breast cancer: a pilot study.
AB  - BACKGROUND: Breast cancer patients may experience disease relapse even 10-20
      years after primary diagnosis. Recurrence is caused by dormant disseminated tumor
      cells (DTCs) in the bone marrow (BM). Whereas chemotherapy is unable to eradicate
      these non-proliferating cells, bisphosponates are currently being discussed as
      eliminating DTCs. The purpose of our study was to: i) analyze the presence of
      DTCs in the BM of breast cancer patients 2-10 years after first diagnosis of
      cancer, and ii) to study the effect of ibandronate on DTCs in those patients with
      DTC persistence. PATIENTS AND METHODS: Bilateral BM aspirates of 54 individuals
      diagnosed 2-10 years ago with breast cancer, but currently disease free, were
      analyzed for DTCs by immunocytochemistry using pan-cytokeratin antibody A45-B/B3.
      Patients with DTC persistence received oral ibandronate treatment (50 mg per day)
      for six months and bilateral BM aspirates were analyzed for DTCs again after
      therapy. RESULTS: DTCs were found in 18/54 (33%) of the patients, with a median
      number of 3 disseminated tumor cells (range 1-6 cells). These 18 patients
      received ibandronate orally for 6 months and 17/18 patients were analyzed for
      DTCs again after therapy. Only 3/17 (18%) patients remained DTC-positive, with
      the detection of 1 (n=2 patients) and 3 DTCs, respectively. These three DTC
      positive patients continued their ibandronate intake for a further six months and
      re-examination of the BM resulted in no detection of DTCs in any of the three
      patients. CONCLUSION: Our pilot study indicates the potential effect of
      ibandronate on DTCs and further studies are needed to demonstrate these findings
      in a larger patient cohort.

PMID- 21965789
TI  - Association of caveolin-1 genotypes with nasopharyngeal carcinoma susceptibility
      in Taiwan.
AB  - BACKGROUND: Caveolin-1 (Cav-1), which has been proposed as a candidate tumor
      suppressor, plays a regulatory role in several signaling pathways. High
      expression of Cav-1 in nasopharyngeal carcinoma (NPC) may enhance tumor cell
      migration and correlate with poor prognosis of the patients, while the genetic
      alterations of Cav-1 during nasopharyngeal carcinogenesis are still largely
      unknown. The aim of this study was to evaluate the association between NPC
      susceptibility and Cav-1 genotypes. PATIENTS AND METHODS: One hundred and seventy
      six patients with NPC and 176 age- and gender-matched healthy controls recruited
      in Taiwan were genotyped and analyzed by PCR-restriction fragment length
      polymorphism. RESULTS: There were significant differences between the NPC and
      control groups in the distributions of the genotypic (p=0.0019) and allelic
      frequencies (p=2.5 10(-4)) in the Cav-1 T29107A (rs7804372) polymorphism.
      CONCLUSION: In this first report of Cav-1 involvement in NPC the A allele of Cav
      1 T29107A is found to be protective against the development of NPC and may be a
      novel useful genomic marker for early screening and prediction of NPC.

PMID- 21965790
TI  - An evaluation of prognostic value of death-associated protein kinase 1 in breast
      cancer.
AB  - BACKGROUND: The benefit of tissue microarray (TMA) is its capability to analyse
      large numbers of tissue samples in a uniform fashion. This study was designed to
      evaluate the capability of TMA for analyzing the status of death-associated
      protein kinase 1 (DAPK1) in breast cancer patient and to explore its potential in
      the management of breast cancer. PATIENTS AND METHODS: Over a 60-month period,
      tissue specimens of 99 patients with primary invasive breast cancer were
      selected. Tissue microarray (TMA) was applied to detect the DAPK1 expression. The
      data for the other clinicopathologic variables, including age, histological
      grading, estrogen receptor status and TNM staging were also recorded. RESULTS:
      Tumor in 11 patients (11.1%) scored 1 for DAPK1 expression, 55 patients (55.6%)
      scored 2 and 33 (33.3%) scored 3. We found no obvious link between DAPK1
      expression and age, histologic grading, primary tumor staging, lymph node status,
      estrogen receptor and TNM stage. TNM staging was found to be significantly linked
      to the overall five-year survival rate through multivariate analysis. CONCLUSION:
      DAPK1 expression did not show any meaningful value in predicting outcome for
      patients with breast cancer.

PMID- 21965808
TI  - Prevalence and predictors of microalbuminuria in Jamaican children with sickle
      cell disease.
AB  - OBJECTIVE: To determine the prevalence and predictors of microalbuminuria (MA)
      (urine albumin-creatinine ratios (ACRs) of 30-300 ug/mg) in children with
      homozygous sickle cell (Hb SS) disease in Jamaica. PATIENTS AND METHODS: 244
      children with Hb SS disease were screened for MA. Blood samples and a
      retrospective review of patient records were used to determine haematological,
      biochemical and clinical correlates for MA. RESULTS: The prevalence of MA was
      18.4%. The youngest child with MA was 2.8 years old. The distribution of urine
      ACRs was right skewed and normalised by natural log transformation. Abnormal
      urine ACRs ranged from 32 to 260 ug/mg. In univariable analyses with log ACR as
      outcome, ever having dactylitis (beta=0.44; 95% CI 0.08 to 0.80; p<0.02),
      glomerular hyperfiltration (beta=0.6; 95% CI 0.26 to 0.94; p<0.001), age
      (beta=0.07; 95% CI 0.01 to 0.12; p<0.02), estimated glomerular filtration rate
      (eGFR) (beta=0.01; 95% CI 0.005 to 0.02; p<0.001), haemoglobin concentration
      (beta=-0.18; 95% CI -0.34 to -0.02; p<0.03) and haemoglobin F (beta=-0.03; 95% CI
      -0.05 to -0.003; p<0.04) were significantly associated with MA but lactate
      dehydrogenase (a marker of haemolysis) was not. Adjusting for gender, age
      (beta=0.08; 95% CI 0.02 to 0.15; p=0.01), eGFR (beta=0.01; 95% CI 0.001 to 0.01;
      p=0.03) and body mass index (beta=-0.16; 95% CI -0.28 to -0.03; p=0.02) were
      predictors of MA. CONCLUSIONS: MA is seen as early as 2.8 years in children with
      sickle cell disease. Risk factors for MA include glomerular hyperfiltration,
      nutritional factors and vaso-occlusion but not haemolysis. Interventions
      addressing these factors may be useful.

PMID- 21965809
TI  - Diagnosis and outcome of children admitted to a paediatric intensive care unit
      with unexplained coma.

PMID- 21965810
TI  - Capillary TSH screening programme for Down's syndrome in Scotland, 1997-2009.
AB  - OBJECTIVES: To assess uptake of community-based capillary thyroid stimulating
      hormone (TSH) screening in Scotland and determine the optimal frequency of
      screening, the justification for preschool screening and strategies for
      treatment. METHODS: Subjects with Down's syndrome aged 1-19 years underwent
      capillary TSH measurement. Clinical and biochemical data were collected using
      proformas. RESULTS: 5742 capillary TSH tests were performed on 1329 children in
      1997-2009, increasing from 183 children from two health boards tested in 1997 to
      630 from 13 health boards tested in 2009. Of 132 children referred by the
      screening laboratory with elevated capillary TSH, 98 (M:F ratio 1:1.2, median
      (range) age 8.9 (0.9-17.9) years) had adequate documentation and 76 had thyroid
      dysfunction (defined as venous TSH >6 mU/l), giving a prevalence of not less than
      5.7%. Fifty-six (57%) had tested negative during the previous year, 8 (8%) tested
      positive on their first screening test and 23/67 (34%) were thyroid peroxidase
      autoantibody negative on initial venous blood. Two of the 13 (13%) preschool
      children were severely hypothyroid (venous TSH 71 and 283 mU/l). Of patients with
      venous TSH 6-10.9 (n=27), 11.0-20.9 (n=25) and >= 21.0 mU/l (n=24) following
      referral, initial/subsequent treatment with thyroxine was given in 3/8, 15/5 and
      21/1, respectively. CONCLUSION: Capillary TSH screening in Down's syndrome is
      eminently feasible and should be performed annually from 1 year of age. Nearly
      all subjects with initial venous TSH >= 11.0 mU/l will require thyroxine
      treatment but most with TSH 6-10 mU/l only require surveillance initially.

PMID- 21965811
TI  - Validation of a clinical algorithm to identify neonates with severe illness
      during routine household visits in rural Bangladesh.
AB  - BACKGROUND: To validate a clinical algorithm for community health workers (CHWs)
      during routine household surveillance for neonatal illness in rural Bangladesh.
      METHODS: Surveillance was conducted in the intervention arm of a trial of newborn
      interventions. CHWs assessed 7587 neonates on postnatal days 0, 2, 5 and 8 and
      identified neonates with very severe disease (VSD) using an 11-sign algorithm. A
      nested prospective study was conducted to validate the algorithm (n=395).
      Physicians evaluated neonates to determine whether newborns with VSD needed
      referral. The authors calculated algorithm sensitivity and specificity in
      identifying (1) neonates needing referral and (2) mortality during the first 10
      days of life. RESULTS: The 11-sign algorithm had sensitivity of 50.0% (95% CI
      24.7% to 75.3%) and specificity of 98.4% (96.6% to 99.4%) for identifying
      neonates needing referral-level care. A simplified 6-sign algorithm had
      sensitivity of 81.3% (54.4% to 96.0%) and specificity of 96.0% (93.6% to 97.8%)
      for identifying referral need and sensitivity of 58.0% (45.5% to 69.8%) and
      specificity of 93.2% (92.5% to 93.7%) for screening mortality. Compared to our 6
      sign algorithm, the Young Infant Study 7-sign (YIS7) algorithm with minor
      modifications had similar sensitivity and specificity. CONCLUSION: Community
      based surveillance for neonatal illness by CHWs using a simple 6-sign clinical
      algorithm is a promising strategy to effectively identify neonates at risk of
      mortality and needing referral to hospital. The YIS7 algorithm was also validated
      with high sensitivity and specificity at community level, and is recommended for
      routine household surveillance for newborn illness. ClinicalTrials.gov no.
      NCT00198627.

PMID- 21965812
TI  - Neuroimaging: what neuroradiological features distinguish abusive from non
      abusive head trauma? A systematic review.
AB  - OBJECTIVES: To identify the evidence base behind the neuroradiological features
      that differentiate abusive head trauma (AHT) from non-abusive head trauma (nAHT).
      DESIGN: Systematic review. SETTING: Literature search of 14 databases, websites,
      textbooks, conference abstracts and references (1970-February 2010). Studies had
      two independent reviews (three if disputed) and critical appraisal. PATIENTS:
      Primary comparative studies of children <11 years old hospitalised with AHT and
      nAHT diagnosed on CT or MRI. MAIN OUTCOME MEASURES: Neuroradiological features
      that differentiated AHT from nAHT. RESULTS: 21 studies of children predominantly
      <3 years old were analysed. Subdural haemorrhages (SDH) were significantly
      associated with AHT (OR 8.2, 95% CI 6.1 to 11). Subarachnoid haemorrhages were
      seen equally in AHT and nAHT and extradural haemorrhages (EDH) were significantly
      associated with nAHT (OR for AHT 0.1, 95% CI 0.07 to 0.18). Multiple (OR 6, 95%
      CI 2.5 to 14.4), interhemispheric (OR 7.9, 95% CI 4.7 to 13), convexity (OR 4.9,
      95% CI 1.3 to 19.4) and posterior fossa haemorrhages (OR 2.5, 95% CI 1 to 6) were
      associated with AHT. Hypoxic-ischaemic injury (HII) (OR 3.7, 95% CI 1.4 to 10)
      and cerebral oedema (OR 2.2, 95% CI 1.0 to 4.5) were significantly associated
      with AHT, while focal parenchymal injury was not a discriminatory feature. SDH of
      low attenuation were more common in AHT than in nAHT. CONCLUSION: Multiple SDH
      over the convexity, interhemispheric haemorrhages, posterior fossa SDH, HII and
      cerebral oedema are significantly associated with AHT and should be considered
      together with clinical features when identifying the condition.

PMID- 21965814
TI  - "Top 5" lists top $5 billion.

PMID- 21965813
TI  - British National Formulary for Children: the risk of inappropriate paracetamol
      prescribing.
AB  - BACKGROUND: Paracetamol is the most commonly prescribed medicine for children.
      Age-based dosing guidelines can lead to inappropriate dosing. METHODS: A review
      of age-based guidelines for paracetamol in the British National Formulary for
      Children (BNFC) 2011-2012 was undertaken. Single and cumulative daily doses of
      paracetamol for boys and girls at 9th, 50th and 91st centiles for weight were
      calculated for the age groups 1-3 months, 3-12 months, 1-6 years and 6-12 years.
      RESULTS: For children at the 9th centile, aged 3 months and above, doses were
      above recommended single and cumulative daily dose therapeutic limits when given
      the highest dose specified for their age. For children at the 91st centile at all
      ages, doses were below recommended single and cumulative daily dose therapeutic
      limits when given the lowest dose specified for their age. CONCLUSIONS:
      Underweight and overweight children are at risk of inappropriate paracetamol
      administration based on BNFC age-based dosing instructions.

PMID- 21965815
TI  - Progress in the genetics of ankylosing spondylitis.
AB  - Ankylosing spondylitis (AS) is a common, highly heritable, inflammatory
      arthropathy. In addition to being strongly associated with HLA-B27, a further 13
      genes have been robustly associated with the disease. These genes highlight the
      involvement of the IL-23 pathway in disease pathogenesis, and indicate overlaps
      between the pathogenesis of AS, and of inflammatory bowel disease. Genetic
      associations in B27-positive and -negative disease are similar, with the main
      exception of association with ERAP1, which is restricted in association to B27
      positive cases. This restriction, and the known function of ERAP1 in peptide
      trimming prior to HLA Class I presentation, indicates that HLA-B27 is likely to
      operate in AS by a mechanism involving aberrant peptide handling. These advances
      point to several potential novel therapeutic approaches in AS.

PMID- 21965816
TI  - TFRank: network-based prioritization of regulatory associations underlying
      transcriptional responses.
AB  - MOTIVATION: Uncovering mechanisms underlying gene expression control is crucial
      to understand complex cellular responses. Studies in gene regulation often aim to
      identify regulatory players involved in a biological process of interest, either
      transcription factors coregulating a set of target genes or genes eventually
      controlled by a set of regulators. These are frequently prioritized with respect
      to a context-specific relevance score. Current approaches rely on relevance
      measures accounting exclusively for direct transcription factor-target
      interactions, namely overrepresentation of binding sites or target ratios. Gene
      regulation has, however, intricate behavior with overlapping, indirect effect
      that should not be neglected. In addition, the rapid accumulation of regulatory
      data already enables the prediction of large-scale networks suitable for higher
      level exploration by methods based on graph theory. A paradigm shift is thus
      emerging, where isolated and constrained analyses will likely be replaced by
      whole-network, systemic-aware strategies. RESULTS: We present TFRank, a graph
      based framework to prioritize regulatory players involved in transcriptional
      responses within the regulatory network of an organism, whereby every regulatory
      path containing genes of interest is explored and incorporated into the analysis.
      TFRank selected important regulators of yeast adaptation to stress induced by
      quinine and acetic acid, which were missed by a direct effect approach. Notably,
      they reportedly confer resistance toward the chemicals. In a preliminary study in
      human, TFRank unveiled regulators involved in breast tumor growth and metastasis
      when applied to genes whose expression signatures correlated with short interval
      to metastasis.

PMID- 21965817
TI  - Supporting tool suite for production proteomics.
AB  - SUMMARY: The large amount of data produced by proteomics experiments requires
      effective bioinformatics tools for the integration of data management and data
      analysis. Here we introduce a suite of tools developed at Vanderbilt University
      to support production proteomics. We present the Backup Utility Service tool for
      automated instrument file backup and the ScanSifter tool for data conversion. We
      also describe a queuing system to coordinate identification pipelines and the
      File Collector tool for batch copying analytical results. These tools are
      individually useful but collectively reinforce each other. They are particularly
      valuable for proteomics core facilities or research institutions that need to
      manage multiple mass spectrometers. With minor changes, they could support other
      types of biomolecular resource facilities.

PMID- 21965818
TI  - Fast filtering for RNA homology search.
AB  - MOTIVATION: Homology search for RNAs can use secondary structure information to
      increase power by modeling base pairs, as in covariance models, but the resulting
      computational costs are high. Typical acceleration strategies rely on at least
      one filtering stage using sequence-only search. RESULTS: Here we present the
      multi-segment CYK (MSCYK) filter, which implements a heuristic of ungapped
      structural alignment for RNA homology search. Compared to gapped alignment, this
      approximation has lower computation time requirements (O(N4) reduced to O(N3),
      and space requirements (O(N3) reduced to O(N2). A vector-parallel implementation
      of this method gives up to 100-fold speed-up; vector-parallel implementations of
      standard gapped alignment at two levels of precision give 3- and 6-fold speed
      ups. These approaches are combined to create a filtering pipeline that scores RNA
      secondary structure at all stages, with results that are synergistic with
      existing methods.

PMID- 21965819
TI  - Unsupervised detection of genes of influence in lung cancer using biological
      networks.
AB  - MOTIVATION: Lung cancer is often discovered long after its onset, making
      identifying genes important in its initiation and progression a challenge. By the
      time the tumors are discovered, we only observe the final sum of changes of the
      few genes that initiated cancer and thousands of genes that they have influenced.
      Gene interactions and heterogeneity of samples make it difficult to identify
      genes consistent between different cohorts. Using gene and gene-product
      interaction networks, we propose a principled approach to identify a small subset
      of genes whose network neighbors exhibit consistently high expression change (in
      cancerous tissue versus normal) regardless of their own expression. We
      hypothesize that these genes can shed light on the larger scale perturbations in
      the overall landscape of expression levels. RESULTS: We benchmark our method on
      simulated data, and show that we can recover a true gene list in noisy
      measurement data. We then apply our method to four non-small cell lung cancer and
      two pancreatic cancer cohorts, finding several genes that are consistent within
      all cohorts of the same cancer type. CONCLUSION: Our model is flexible, robust
      and identifies gene sets that are more consistent across cohorts than several
      other approaches. Additionally, our method can be applied on a per-patient basis
      not requiring large cohorts of patients to find genes of influence. Our approach
      is generally applicable to gene expression studies where the goal is to identify
      a small set of influential genes that may in turn explain the much larger set of
      genome-wide expression changes.

PMID- 21965820
TI  - Lower confidence bounds for prediction accuracy in high dimensions via AROHIL
      Monte Carlo.
AB  - MOTIVATION: Implementation and development of statistical methods for high
      dimensional data often require high-dimensional Monte Carlo simulations.
      Simulations are used to assess performance, evaluate robustness, and in some
      cases for implementation of algorithms. But simulation in high dimensions is
      often very complex, cumbersome and slow. As a result, performance evaluations are
      often limited, robustness minimally investigated and dissemination impeded by
      implementation challenges. This article presents a method for converting complex,
      slow high-dimensional Monte Carlo simulations into simpler, faster lower
      dimensional simulations. RESULTS: We implement the method by converting a
      previous Monte Carlo algorithm into this novel Monte Carlo, which we call AROHIL
      Monte Carlo. AROHIL Monte Carlo is shown to exactly or closely match pure Monte
      Carlo results in a number of examples. It is shown that computing time can be
      reduced by several orders of magnitude. The confidence bound method implemented
      using AROHIL outperforms the pure Monte Carlo method. Finally, the utility of the
      method is shown by application to a number of real microarray datasets.

PMID- 21965821
TI  - HHfrag: HMM-based fragment detection using HHpred.
AB  - MOTIVATION: Over the last decade, both static and dynamic fragment libraries for
      protein structure prediction have been introduced. The former are built from
      clusters in either sequence or structure space and aim to extract a universal
      structural alphabet. The latter are tailored for a particular query protein
      sequence and aim to provide local structural templates that need to be assembled
      in order to build the full-length structure. RESULTS: Here, we introduce HHfrag,
      a dynamic HMM-based fragment search method built on the profile-profile
      comparison tool HHpred. We show that HHfrag provides advantages over existing
      fragment assignment methods in that it: (i) improves the precision of the
      fragments at the expense of a minor loss in sequence coverage; (ii) detects
      fragments of variable length (6-21 amino acid residues); (iii) allows for gapped
      fragments and (iv) does not assign fragments to regions where there is no clear
      sequence conservation. We illustrate the usefulness of fragments detected by
      HHfrag on targets from most recent CASP.

PMID- 21965822
TI  - Kaviar: an accessible system for testing SNV novelty.
AB  - SUMMARY: With the rapidly expanding availability of data from personal genomes,
      exomes and transcriptomes, medical researchers will frequently need to test
      whether observed genomic variants are novel or known. This task requires
      downloading and handling large and diverse datasets from a variety of sources,
      and processing them with bioinformatics tools and pipelines. Alternatively,
      researchers can upload data to online tools, which may conflict with privacy
      requirements. We present here Kaviar, a tool that greatly simplifies the
      assessment of novel variants. Kaviar includes: (i) an integrated and growing
      database of genomic variation from diverse sources, including over 55 million
      variants from personal genomes, family genomes, transcriptomes, SNV databases and
      population surveys; and (ii) software for querying the database efficiently.

PMID- 21965824
TI  - Multicentric evaluation of a second generation assay to detect antiviral
      citrullinated peptide antibodies: a collaborative study by the Forum
      Interdisciplinare per la Ricerca nelle Malattie Autoimmuni.
AB  - AIMS: A novel immunoenzymatic assay using viral citrullinated peptides derived
      from Epstein-Barr virus-encoded proteins (viral citrullinated peptide 2 (VCP2))
      has been developed and evaluated by means of a multicentre collaborative study.
      METHODS: Three hundred nine sera from patients with established rheumatoid
      arthritis (RA), 36 with early arthritis, 12 with juvenile arthritis and 453
      controls were tested for VCP2 and cyclic citrullinated peptide (CCP) antibodies.
      RESULTS: The VCP2 assay showed 78.3% sensitivity and 97.1% specificity. VCP2 and
      CCP had a high concordance rate in patients with RA (88%) and controls (97%).
      However, 36 RA sera were positive in the CCP assay but negative on VCP2, and two
      RA sera reacted only on VCP2. CONCLUSIONS: The new VCP2 assay is endowed with
      high sensitivity and specificity. VCP2-positive RA sera are mostly but not
      completely contained in the CCP-positive population. Studies are in progress to
      establish whether the VCP2 assay can detect clinically distinct subsets of
      patients with RA.

PMID- 21965825
TI  - A clinicopathological aspect of primary small-cell carcinoma of the uterine
      cervix: a single-centre study of 25 cases.
AB  - AIMS: Small-cell carcinoma is a variant of poorly differentiated neuroendocrine
      carcinoma. Primary small-cell carcinoma of the cervix (SCCC) is recognised as a
      rare and aggressive malignant tumour with poor prognosis. In this study, the
      authors report 25 Chinese cases of SCCC, with a particular focus on their
      clinical and pathological characteristics. MATERIAL AND METHODS: The records of
      25 patients from 4075 Chinese patients with cervical cancer were collected and
      reviewed, including the patients' age, initial symptoms, cervical tumour size,
      International Federation of Gynaecology and Obstetrics clinical stage, lymph-node
      metastasis, treatments and follow-up results. Immunohistochemical detection was
      performed for cytokeratin, epithelial membrane antigen, neuron-specific enolase
      (NSE), synaptophysin (Syn), chromogranin A (CgA), neuronal cell adhesion
      molecules (CD56), thyroid transcriptional factor-1 and S100 protein (S100).
      RESULTS: The median age of 25 patients with SCCC was 43.7 years. The most common
      symptom was abnormal vaginal bleeding. Histologically, there were 19 'homogenous'
      SCCC samples and six samples of SCCC mixed with adenocarcinoma. The proportion of
      SCCC samples with positive immunoreactivity were 100.0% for NSE, 96.0% for Syn,
      68.0% for CD56, 76.0% for CgA, 40.0% for thyroid transcriptional factor-1, 84.0%
      for epithelial membrane antigen, 68.0% for cytokeratin and 8.0% for S100,
      respectively. Every patient received one to three types of treatments, including
      surgery, chemotherapy and radiotherapy. The median survival time of patients was
      20.9 months after diagnosis. CONCLUSION: The higher proportion of positive
      labelling of Syn, CD56, CgA, and NSE in SCCC implicated that they are valuably
      applied in a differential diagnosis of the malignancy. The patients with SCCC
      receive one to three types of therapies, including surgery, chemotherapy and
      radiotherapy, and have a poor prognosis.

PMID- 21965826
TI  - Changes in gastrointestinal carriage of multi-resistant Gram-negative bacilli in
      a predominantly rural population served by a district general hospital.

PMID- 21965827
TI  - Human papillomavirus coinfection in the oral cavity of HIV-infected children.
AB  - AIM: To identify the early presence of human papillomavirus (HPV) DNA in the oral
      cavity of HIV-infected children. METHODS: The study group comprised 50 HIV
      infected children and 50 healthy aged paired controls. Oral mucosa samples were
      collected by swab, and a 450 bp HPV DNA fragment was amplified by PCR, using
      degenerate consensus primers directed to the L1 gene. HPV typing was performed
      using specifics primers for types 6/16 and 11/18. RESULTS: All HPV co-infected
      children had vertical transmission of HIV. HPV DNA was detected in 6/50 (12.0%)
      of HIV children and three control group individuals 3/50 (6.0%) (p>0.01). In the
      HIV group, one had type 11, in the control group one had co-infection of types
      11/16, and the others had type 16 and 18. CONCLUSIONS: Based upon the results, it
      is concluded that HPV DNA may be present in HIV disease, but no association with
      immunosuppression, delivery, or medical records (CD4 cell count, viral load and
      use of highly active antiretroviral therapy) was observed, and no differences
      could be observed between the groups either.

PMID- 21965828
TI  - Benign phyllodes tumour with intraductal papillary growth of the breast in a
      young woman.

PMID- 21965829
TI  - Histological examination in sudden unexpected death in infancy: evidence base for
      histological sampling.
AB  - AIM: Pathologists currently follow the 'Kennedy guidelines' when performing
      autopsies for sudden unexpected death in infancy (SUDI); these include extensive
      histological sampling. This study establishes the frequency with which
      histological examination of visceral organs determines cause of death and
      examines associations between clinical, macroscopic and microscopic findings.
      METHODS: Retrospective review of 546 SUDI autopsies performed for a 10-year
      period (1996-2005) at a single centre. The proportion of cases in which non
      neuropathological histological examination directly determined the cause of death
      was identified, and clinical, macroscopic and histological findings at autopsy
      were compared. RESULTS: Of 510 SUDIs included, 166 cases were explained SUDI, and
      of these, 54% (89/166) were identified solely on microscopic examination, based
      on histology of the lungs in 71 (43%), heart in 13 (8%), liver in 4 (2%) and
      kidneys in 1 (<1%). The proportions of macroscopically normal organs with
      significant histological findings were 26% lungs, 2% heart and 1% each of liver
      and kidneys, but none of spleen, thymus, pancreas or adrenals. Macroscopically
      abnormal organs were more likely to yield significant histological features.
      Symptoms preceding death were more common in cases with significant histological
      findings in lungs, heart, liver and adrenals. CONCLUSION: A non-neuropathological
      cause of death in explained SUDI can be established from histological examination
      of lungs, heart, liver and kidneys. Significant histological abnormalities may be
      detected in selected organs with macroscopically normal appearances. Routine
      histological sampling of other organs in the absence of specific clinical history
      or macroscopic abnormalities has a low yield for establishing cause of death.

PMID- 21965830
TI  - Ovarian non-small cell neuroendocrine carcinoma associated with increased HCG
      beta.

PMID- 21965831
TI  - Endoscopic ultrasound guided transbronchial fine needle aspiration: a French
      Department of Pathology's 4-year experience.
AB  - BACKGROUND: Endobronchial ultrasound (EBUS) guided transbronchial needle
      aspiration (TBNA) is an accurate outpatient procedure used to explore mediastinal
      lymph nodes for lung cancer staging and unexplained mediastinal masses. AIMS AND
      METHODS: A retrospective study was conducted over four years on EBUS-TBNA sampled
      lymph nodes investigated for the staging of lung cancer or unexplained
      mediastinal lymphadenopathies, first using the conventional method (CM) and then
      a liquid based cytology (LBC). RESULTS: Of the 628 specimens (355 patients)
      collected, the overall rate of adequacy was 88% and the diagnosis of malignancy
      was achieved in 43% of cases. The inadequate rate was 6% with LBC and 21% with
      CM. A paraffin cytoblock was available in 80% with LBC and 62% with CM. Of the
      628 aspirates, 270 (43%) were categorised as negative for malignancy including 26
      cases consistent with sarcoidosis, 272 (43%) as malignant, 9 (1.4%) as suspicious
      for non-small-cell carcinoma and 77 as inadequate samples (12%). Of the 272 cases
      diagnosed as malignant, 87 (32%) were classified as non-small-cell carcinoma, 106
      (39%) as adenocarcinoma, 48 (18%) as squamous cell carcinoma and 20 (7%) as small
      cell carcinoma. Five lymphomas, four metastatic melanomas and two carcinoids were
      also diagnosed. CONCLUSIONS: EBUS-TBNA is a reliable method for the staging of
      lung cancer and for unexplained mediastinal mass exploration. The LBC has a lower
      rate of inadequate samples, a better yield of cytoblock for immunohistochemistry
      and a dramatically reduced time requirement for interpretation as compared to CM.

PMID- 21965832
TI  - Handling and reporting of nephrectomy specimens for adult renal tumours: a survey
      by the European Network of Uropathology.
AB  - AIM: To collect information on current practices of European pathologists for the
      handling and reporting of nephrectomy specimens with renal tumours. METHODS AND
      RESULTS: A questionnaire was circulated to the members of the European Network of
      Uropathology, which consists of 343 pathologists in 15 European countries.
      Replies were received from 48% of members. These replies indicated that
      nephrectomy specimens are most often received in formalin. Lymph nodes are found
      in less than 5% of nephrectomy specimens. All respondents give an objective
      measure of tumour size, most commonly in three diameters. The most common method
      to search for capsule penetration is to slice tissue outside the tumour
      perpendicularly into the tumour. The most common sampling algorithm from tumours
      greater than 2 cm is one section for every centimetre of maximum tumour diameter.
      Most respondents use the 2004 WHO renal tumour classification although only
      slightly over half consider small papillary tumours malignant if the diameter is
      greater than 5 mm. The Fuhrman grading system is widely used. Almost all use
      immunohistochemistry for histological typing in some cases, while only 7% always
      use it. The most utilised special stains are CK7 (95%), CD10 (93%), vimentin
      (86%), HMB45 (68%), c-kit (61%) and Hale's colloidal iron (52%). Only 18% use
      other ancillary techniques for diagnosis in difficult cases. CONCLUSIONS: While
      most pathologists appear to follow published guidelines for reporting renal
      carcinoma, there is still a need for the development of consensus and further
      standardisation of practice for contentious areas of specimen handling and
      reporting.

PMID- 21965833
TI  - Estimation of cell density to aid in assessment of percentage cells of a
      particular lineage or of cells expressing a specific antigen in bone marrow
      trephine biopsies.
AB  - The authors aimed to develop a tool to assess total cell numbers in a
      microscope's field of vision, which would provide the denominator for calculating
      the percentage of positive cells for a given antigen in bone marrow trephine
      biopsies (BMTBs) of varying cellularities. Precise estimates of cell densities
      were made from 179 images of BMTBs of varying cellularities using a cell-counting
      software. The estimates were then validated on an independent set of 20 BMTBs.
      Among the 179 images, there was a strong linear association between marrow
      cellularity and cell numbers (Pearson correlation: 0.788). Then standardised cell
      densities (cells/mm(2) of bone marrow) were deduced for BMTBs of varying
      cellularities. In the validation study, the actual and the estimated cell numbers
      correlated strongly (Pearson correlation: 0.990). The cell density estimates
      provided in this study can be adapted for any microscope and the same method can
      be used for calculation of the percentage-positive cells for any antigen.

PMID- 21965834
TI  - Preventive psychiatry within public health.

PMID- 21965835
TI  - Homicide rates and income inequality.

PMID- 21965836
TI  - Observational BALANCE.

PMID- 21965837
TI  - Role of postcards in reducing suicidal behaviour.

PMID- 21965838
TI  - Sudden exertional death in sickle cell trait.

PMID- 21965839
TI  - Thermal stability of functionalized carbon nanotubes studied by in-situ
      transmission electron microscopy.
AB  - The thermal stability of funtionalized carbon nanotubes (CNTs) has been studied
      experimentally by direct in-situ observations using a heating stage in a
      transmission electron microscope, from room temperature (RT) to about 1000 
      degrees C. It was found that the thermal stability of the functionalized CNTs was
      significantly reduced during the in-situ heating process. Their average diameter
      dramatically expanded from RT to about 500  degrees C, and then tended to be
      stable until about 1000  degrees C. The X-ray energy dispersive spectroscopy
      analysis suggested that the diameter expansion was associated with coalescence of
      the carbon structure instead of deposition with additional foreign elements
      during the heating process.

PMID- 21965840
TI  - Venereology in India.
AB  - Venereology-the study of venereal diseases or more recently, the sexually
      transmitted infections (STI) includes a variety of pathogens namely viruses,
      bacteria, fungi and protozoa for which the common factor is the mode of
      transmission and acquisition: Sexual relations between human beings. Medical and
      other historians have often suggested that well-known diseases such as syphilis,
      gonorrhea, chancroid and lymphogranuloma venereum have existed since earliest
      times. However, it is difficult to identify modern disease entities based on
      written historical record. Studying the origin of STIs helps us to learn the
      political, economic and moral conditions that led to the disease. Effective
      management of STI rests on three pillars of diagnosis, prevention and treatment.
      For most of past 50 years in India, the diagnostic pillar has been the least well
      supported. Until well into present century, diagnosis of STI in India was
      clinical. Treatment of STIs in India followed the methods used in England. Of
      course in the 19(th) century, in many parts of the world, only a few had access
      to modern methods of treatment; in India, there was extensive use of Ayurvedic
      treatment with traditional medicines. This article thus gives just an overview
      and evolution of venereology in India with regard to venereal diseases (now more
      often known as STIs/disease), control measures, academic, association and journal
      development and finally future perspective.

PMID- 21965841
TI  - Cytokines in dermatology - a basic overview.
AB  - Cytokines are non-immunoglobulin proteins and glycoproteins produced by a wide
      variety of cells, in response to any immune stimulus. Cytokines are signaling
      molecules that send downstream signals to various cells through a number of
      signal transduction pathways and act further by binding to specific membrane
      receptors (cytokine receptors) on the cell surface. They are emergency molecules,
      which are released transiently. Cytokines play an important role in cellular
      communication. They regulate immunity, inflammation, cell activation, cell
      migration, cell proliferation, apoptosis, and hematopoiesis. However, when
      released persistently they can produce chronic disease.

PMID- 21965842
TI  - Neurocutaneous syndrome: a prospective study.
AB  - BACKGROUND: Neurocutaneous syndromes (NCS) are a group of genetic disorders that
      produce a variety of developmental abnormalities of the skin along with an
      increased risk of neurological complications. Cutaneous manifestations usually
      appear early in life and progress with time, but neurological features generally
      present at a later age. There is a paucity of data regarding the evolution of
      skin lesions and their correlation with the central nervous system involvement in
      children. AIM: The primary objective was to track the course of skin lesions in
      various forms of NCS in the pediatric age group. Our secondary aim was to assess
      whether there was any predictive value of the lesions in relation to the
      neurological manifestations. MATERIALS AND METHODS: This prospective longitudinal
      study was conducted at a tertiary care pediatric dermatology referral clinic of
      the Institute of Child Health, Kolkata, West Bengal. Children between the age
      group 0 and 12 years were included in the study on the basis of standard
      diagnostic criteria for different NCS, during the period from March, 2000 to
      February, 2004, and each of the enrolled cases were followed up for a duration of
      six years. RESULTS: The study population comprised of 67 children (35 boys, 32
      girls).The mean age of presentation was 33.8+/-27.8 months (range 10 days to 111
      months). The various forms of NCS observed was neurofibromatosis 1(NF1) (n=33),
      tuberous sclerosis complex (TSC) (n=23), Sturge Weber syndrome (n=6), ataxia
      telangiectasia (n=2), PHACE syndrome (n=1), incontinentia pigmenti (n=1), and
      hypomelanosis of Ito (n=1). The presentations were varied, ranging from
      predominantly cutaneous to primarily neurological, depending on the disease
      entity and age group concerned. There was a significant increase in the number of
      cafe au lait macules (CALMs) with time (P=0.0002) in NF1, unlike that of
      hypopigmented macules of TSC (P=0.15). Statistically, no relation was documented
      between the evolution of skin lesions and neurological manifestations in the
      major groups. CONCLUSION: As NCS is not an uncommon disease in children, it is
      always necessary to find out the subtle neurological signs, whenever we observe
      any case with cutaneous markers suggestive of NCS. In addition, it is a must to
      do a detailed dermatological examination in a child with central nervous system
      involvement, in the pediatric population. However, the neurological course cannot
      be predicted from skin lesions.

PMID- 21965843
TI  - Melasma: a clinico-epidemiological study of 312 cases.
AB  - BACKGROUND: Melasma is an acquired increased pigmentation of the skin,
      characterized by gray-brown symmetrical patches, mostly in the sun-exposed areas
      of the skin. The pathogenesis is unknown, but genetic or hormonal influences with
      UV radiation are important. AIMS: Our present research aims to study the clinico
      epidemiological pattern and the precipitating or provocation factors in melasma.
      MATERIALS AND METHODS: A total of 312 patients were enrolled for the study over a
      period of one year. RESULTS: The mean age of patients with melasma was 33.45
      years, ranging from 14 to 54 years. There was female preponderance with a female
      to male ratio of approximately 4 : 1. The mean age of onset was 29.99 years, with
      the youngest and oldest being 11 and 49 years, respectively. The patients sought
      medical treatment on an average of 3.59 years after appearance of melasma. About
      55.12% of our patients reported that their disease exacerbated during sun
      exposure. Among 250 female patients, 56 reported pregnancy and 46 reported oral
      contraceptive as the precipitating factors. Only 34 patients had given history of
      exacerbation of melasma during pregnancy. A positive family history of melasma
      was observed in 104 (33.33%) patients. Centrofacial was the most common pattern
      (55.44%) observed in the present study. Wood light examination showed the dermal
      type being the most common in 54.48% and epidermal and mixed were seen in 21.47%
      and 24.03% of the cases, respectively. We tried to find an association with
      endocrinal diseases and observed that 20 of them had hypothyroidism. CONCLUSION:
      The exact cause of melasma is unknown. However, many factors have been implicated
      in the etiopathogenesis of this disorder. Here we try to identify the causative
      factors and provocation to develop melasma.

PMID- 21965844
TI  - Clinical evaluation of patients patch tested with plant series: a prospective
      study.
AB  - BACKGROUND: Plants are ubiquitous in nature and are essential for human life,
      though some do have detrimental effects. In India, there are various indigenous
      and foreign plants that are well known to cause dermatitis, Parthenium
      hysterophorus being the foremost. AIMS OF THE STUDY: To study the clinical
      features of patients presenting with plant dermatitis and evaluate plant allergen
      series patch test results. MATERIALS AND METHODS: 50 patients with suspected
      plant dermatitis were evaluated regarding evolution of dermatitis, precipitating
      factors and contact with various plants. 31 patients (62%) complained of photo
      sensitivity and 24 (48%) had involvement of sun-exposed areas. Our provisional
      diagnoses included allergic contact dermatitis in 16, air borne contact
      dermatitis in 9, phytophotodermatitis in 7, photodermatitis in 6, airborne
      contact dermatitis to other causes in 4, phytodermatitis in 3. Patients were
      patch tested with Indian standard series of allergens as well as plant allergen
      series consisting of common allergenic plants of local flora in and around
      Manipal and also with plants strongly suspected by the patient. 35 tested
      positive with maximum positives (26 patients, i.e., 52%) to Parthenium
      hysterophorus (Compositae). RESULTS: The result of patch testing was correlated
      with the history and clinical examination and relevance established. CONCLUSIONS:
      Majority of the patients with clinically suspected plant dermatitis belonged to
      3(rd) or 4(th) decade and Parthenium was the leading plant allergen Sensitization
      to Leguminosae plants and Hopea ponga, seen in 9 cases, have not been reported
      earlier in literature.

PMID- 21965845
TI  - A clinical study of 125 patients with phrynoderma.
AB  - BACKGROUND: Phrynoderma is a type of follicular hyperkeratosis. Various
      nutritional deficiency disorders have been implicated in the etiology of
      phrynoderma. AIM: To determine clinical features of phrynoderma and its
      association with nutritional deficiency signs. MATERIALS AND METHODS: A cross
      sectional descriptive study of 125 consecutive patients with phrynoderma
      attending the outpatient department (OPD) of dermatology was conducted in a
      tertiary care hospital. In all patients, a detailed history was taken and
      cutaneous examination findings such as distribution, sites of involvement,
      morphology of the lesions, and signs of nutritional deficiencies were noted.
      RESULTS: The proportion of patients with phrynoderma attending the OPD was 0.51%.
      There were 79 males and 46 females. Age of the patients was in the range of 3-26
      years with a mean of 10 +/- 4.3 years. The lesions were asymptomatic in 114
      (91.2%) patients. The distribution of lesions was bilateral and symmetrical in 89
      (71.2%) patients. The disease was localized (elbows, knees, extensor extremities,
      and/or buttocks) in 106 (84.8%) patients. The site of onset was elbows in 106
      (84.8%) patients. The lesions were discrete, keratotic, follicular, pigmented or
      skin colored, acuminate papules in all patients. Signs of vitamin A and vitamin B
      complex deficiency were present in 3.2% and 9.6% patients, respectively.
      Epidermal hyperkeratosis, follicular hyperkeratosis, and follicular plugging were
      present in the entire biopsy specimen. CONCLUSION: Phrynoderma is a disorder with
      distinctive clinical features and can be considered as a multifactorial disease
      involving multiple nutrients, local factors like pressure and friction, and
      environmental factors in the setting of increased nutritional demand.

PMID- 21965846
TI  - A clinical evaluation of skin tags in relation to obesity, type 2 diabetis
      mellitus, age, and sex.
AB  - BACKGROUND: Skin tags (STs) have been investigated as a marker of type 2 diabetes
      mellitus (DM), yet the relation of STs to obesity is still a matter of
      controversy. AIM: The aim of the study is to explore the relation of number, size
      and color of STs to obesity, diabetes, sex and age in one study. METHODS: The
      study included 245 nondiabetic (123 males and 122 females) and 276 diabetic (122
      males and 154 females) subjects. We recorded age, sex, body mass index (BMI),
      relevant habits, STs color, size, and number in different anatomical sites.
      RESULTS: The presence and the mean number of STs was more in obese than nonobese
      participants (P = 0.006 and P < 0.001, respectively) and was not affected by sex.
      However, the number increased significantly with age. The presence of mixed-color
      STs was related to obese (P < 0.001) participants. Multivariate logistic
      regression revealed that only BMI was significantly associated with the mixed
      color STs (OR = 3.5, P < 0.001). The association of DM (OR = 1.7) with mixed
      color STs was nonsignificant (P = 0.073). Neither age nor sex had any association
      with mixed-color STs. Within cases that developed mixed-color STs, the
      multivariate analysis showed that only BMI had a significant correlation to the
      number of STs (beta = 0.256, P = 0.034). CONCLUSION: The study showed that not
      only the number but also the presence of mixed-color ST was related to obesity,
      but not to diabetes. The presence of mixed-color STs in nondiabetic subjects
      needs close inspection of BMI.

PMID- 21965847
TI  - Comparison of risk factors of single Basal cell carcinoma with multiple Basal
      cell carcinomas.
AB  - BACKGROUND: Basal cell carcinoma (BCC) is the most common malignant skin tumor.
      Although mortality attributable to BCC is not high, the disease is responsible
      for considerable morbidity. There is evidence that the number of patients who
      develop more than one BCC is increasing. AIMS: The aim of this study was to
      elucidate possible risk factors for developing Multiple BCC. PATIENTS AND
      METHODS: Patients with histologically proven BCC (n = 218) were divided into two
      groups (single BCC and Multiple BCC) according to the number of their tumors and
      their profile were reviewed. Probable risk factors were compared between these
      two groups. RESULTS: Among 33 evaluated risk factors, mountainous area of birth,
      past history of BCC, history of radiotherapy (in childhood due to tinea capitis),
      abnormal underlying skin at the site of tumor, and pigmented pathologic type
      showed significant differences between the two groups. CONCLUSIONS: The high rate
      of additional occurrences of skin cancers among patients with previously
      diagnosed BCC emphasizes the need of continued follow-up of these individuals.
      Those with higher risk require closest screening.

PMID- 21965848
TI  - A study of psoriasis and quality of life in a tertiary care teaching hospital of
      kottayam, kerala.
AB  - BACKGROUND: Psoriasis is a chronic skin disease which has an impact on health
      related quality of life (QoL). The psoriasis disability index (PDI) is a simple
      15-item questionnaire which is used to assess overall psoriasis disability.
      OBJECTIVES: (1) To assess the health-related QoL among patients with psoriasis,
      attending dermatology OPD of Medical College Hospital, Kottayam. (2) To find out
      the association of QoL with age and gender. MATERIALS AND METHODS: This was a
      descriptive case series study conducted in Dermatology OPD of Medical College
      Hospital, Kottayam, Kerala. Psoriasis patients attending the Dermatology OPD of
      Medical College Hospital for 2 months were assessed. RESULTS: Out of the total 32
      patients, 56.2% were males, whose mean age was 45; 72% were married, 47% had
      education above plus two and were employed. Also, 34% had income above Rs. 3000
      per month. Among the PDI subsets, daily activities were affected the most
      (90.6%), followed by work (84.4%), leisure activities (71.9%), problems with
      treatment (68.7%) and the least affected was personal relations (62.5%). Overall
      PDI score (median 14.5, interquartile range 4.5-22) showed that the QoL was
      affected in 75% of which 9.4% were mild (score < 9), 31.2% were moderate (score
      10-18) and 34.4% were severe (score > 18). There was no association between the
      total PDI score and age or gender. CONCLUSION: QoL was affected in 75% of
      psoriasis patients. There was no association between QoL and age or gender.

PMID- 21965849
TI  - Utility of dermoscopy in alopecia areata.
AB  - BACKGROUND: Alopecia areata (AA) shows several well-defined dermoscopic features
      which may help in confirming diagnosis in AA. AIMS: We carried out a study to
      examine the dermoscopic features of AA and develop a protocol for diagnosis of AA
      by dermoscopy. MATERIALS AND METHODS: Dermoscopy was performed in 66 patients
      with AA. Hanse HVS-500NP dermoscope (magnification of *32 and *140) was used.
      RESULTS: The mean age of the patients (46 males and 20 females) was 26.85 years.
      The mean age of onset was 25.15 years. The mean duration of alopecia was 10.3
      months. Most common AA in our study was patchy type (57/66, 87.7%). Single patch
      was seen in 24 patients and multiple patches in 33 patients. Diffuse AA was seen
      in five patients. Ophiasis and alopecia universalis were seen in two patients
      each. Nail changes were fine pitting (4), ridging (2), thinning of nail plate
      (2). Twenty nail dystrophy, distal onycholysis, striate leukonychia and coarse
      pitting were seen in one patient each. Intralesional triamcinolone acetonide was
      the most common therapy offered. Others were oral betamethasone minipulse
      therapy, dexamethasone pulse, minoxidil, anthralin and corticosteroids. The most
      common dermoscopic finding was yellow dots seen in 54 patients (81.8%), followed
      by black dots (44 patients, 66.6%), broken hairs (36 patients, 55.4%), short
      vellus hair (27 patients, 40.9%) and tapering hairs (8 patients, 12.1%).
      CONCLUSIONS: The most common dermoscopic finding of AA in our study was yellow
      dots, followed by black dots, broken hairs, short vellus hair and tapering hairs.
      Dermoscopic findings were not affected by the type of AA or the severity of the
      disease.

PMID- 21965850
TI  - Acquired multifocal tufted angiomas in an immunocompetent young adult.
AB  - Tufted angioma (TA) is a rare benign vascular neoplasm, localized to the skin and
      subcutaneous tissues, occurring primarily on the trunk and extremities of
      children. The lesions are usually asymptomatic but, rarely, paroxysmal painful
      episodes may be associated. The occurrence of eruptive TA is still rarer and had
      been described almost exclusively in association with immunocompromised states.
      We report here a case of acquired painful multifocal tufted angiomas on the face
      and neck in an immunocompetent young adult.

PMID- 21965851
TI  - Painful 20 fingers' onychodistrophy.
AB  - Psoriatic onycho-pachydermo-periostitis (POPP) is a rare subset of psoriatic
      arthritis. It is usually localized to the hands and it is characterized by
      onychodistrophy, soft tissue thickening above the distal phalanx and periosteal
      reaction. The resolution is very slow due to the involvement of nails and bone.
      Low dose methotrexate and anti-tumor necrosis factor-alpha (anti-TNF-alpha)
      agents are the suggested therapies. We report a case of a 53-year-old man
      affected by palmo-plantar slight psoriatic dermatitis, who presented a rapid
      onset of POPP. Rx imaging showed enthesitis and a moderate phalanx erosion with
      articular spaces narrowing and swollen periosteal reaction. A magnetic resonance
      imaging test of the hands showed an initial stage of synovitis and extensive
      periostitis of the distal phalangeal tufts. The patient has been treated with
      oral methotrexate for a month with a rapid clinical improvement and pain
      reduction. As POPP at first manifests as a painful onycodistrophy, it can easily
      be confused with bacterial perionyxis. The delay in making the correct diagnosis,
      and therefore, the delay in giving a proper treatment would mean the progressive
      articular erosion and the permanent invalidation of the patient's ability to use
      his hands.

PMID- 21965852
TI  - Primary cutaneous B-cell lymphoma successfully treated with highly active
      antiretroviral therapy alone: a case report and review of the literature.
AB  - Cutaneous B-cell lymphoma (CBCL) is an unusual skin neoplasm with a great range
      of clinical presentations. Here, we report a case of CBCL in an AIDS patient
      presented as a single and nodular/ulcerative lesion in the perianal area. The
      patient was started on highly active antiretroviral therapy alone with a good
      clinical and oncological response. Two years later, the patient is asymptomatic
      with undetectable viral load and immune reconstitution.

PMID- 21965853
TI  - Topiramate induced pruritus in a patient with alcohol dependence.
AB  - Topiramate is an antiepileptic medication frequently used for the management of
      alcohol dependence and in other psychiatric disorders. Though cutaneous side
      effects are known to occur with it, isolated pure pruritus is rarely reported
      with topiramate in the literature. We wish to report a case of pruritus
      associated with topiramate use in a male with alcohol dependence syndrome.

PMID- 21965854
TI  - Chronic myeloid leukemia in an adult ghanaian with sporadic neurofibromatosis 1.
AB  - Patients with neurofibromatosis type 1 (NF1), a common, progressive, autosomal
      dominant neurocutaneous disorder, are predisposed to malignancies. Several types
      of hematologic malignancies have been described in them. However, to date there
      has been no report to the best of our knowledge of a patient with NF1 developing
      chronic myeloid leukemia (CML). We present an adult Ghanaian with NF1, who
      subsequently developed CML. Relevance of the case report is discussed.

PMID- 21965855
TI  - Hemosiderotic clear-cell acanthoma: a pigmented mimicker.
AB  - The authors report on a case of a 65-year-old man with pigmented clear-cell
      acanthoma located on the right thigh. Dermoscopy disclosed a peculiar picture
      consisting of diffuse black pigmentation with a superficial greyish veil in the
      central portion, dotted-to-globular dark red-black structures mainly located at
      the periphery with a homogenous regular reticular arrangement; peripheral
      translucid desquamation. Dermoscopic features are correlated with the histology,
      where hemosiderin deposits present in a sheet-like arrangement in the
      perivascular papillary dermis and in a band-like disposition in the reticular
      dermis at the base of the lesion can account for the pigmented picture. The
      lesion arose on a trauma-prone skin site; thus the authors believe that traumatic
      irritation may be responsible for the clinical and dermoscopic pictures, giving
      rise to a reaction similar in a way to the Auspitz's sign provocated by trauma
      for psoriasis. Red blood cells extravasation from extremely superficialized
      capillaries may have led to hemosiderin deposition in the papillary and the
      reticular dermis.

PMID- 21965856
TI  - Auricular enlargement: an atypical presentation of old world cutaneous
      leishmaniasis.
AB  - The auricle is an extremely rare site for cutaneous leishmaniasis (CL) in Old
      World, which tends to be a benign disease with self-healing small nodules such as
      the "oriental sore". However, in the New World, there is a type of CL of the ear,
      named as "chiclero's ulcer" which is caused by Leishmania mexicana. Herein, we
      describe a case of massive auricular enlargement due to Old World CL.

PMID- 21965857
TI  - A forgotten disease reminds itself with a rare complication.
AB  - Diagnosed cases of sexually transmitted diseases (STD) represent tip of the
      iceberg and Donovanosis in one of them. Donovanosis, in most cases is obvious
      clinically, but rely for its confirmation on the demonstration of donovan bodies
      in histological sections and cytological preparation. In an extremely rare
      setting, this disease may get complicated by the development of squamous cell
      carcinoma. We report this occurrence in an 18-year-old girl to review the
      currently forgotten status of donovanosis amongst the STDs and the poor outcome
      of the disease if left untreated.

PMID- 21965858
TI  - Seborrheic keratoses in five elderly patients: an appearance of raindrops and
      streams.
AB  - Five Chinese patients were found to have a linear, splayed, vertical pattern of
      lesions on their back, chest and abdomen. These lesions were clinically and
      pathologically diagnosed as seborrheic keratosis. The mean age of our patients
      was 77.6 years. During the follow-up period of 12-20 years, the lesions appeared
      to increase with age, and no malignant changes were observed on these sites.
      These patients had no serious underlying medical problems or malignant neoplasm,
      except for one patient with duodenal ulcer. While we are uncertain as to the
      cause of this patterning of seborrheic keratoses, we believe that it is distinct
      from previously reported patterns; this will contribute to research on the
      pathogenesis of seborrheic keratosis.

PMID- 21965859
TI  - A solitary crateriform ulcer of the lower lip: a case report with review of
      literature.
AB  - Keratoacanthoma (KA) is a relatively common skin lesion. We report a case of KA
      mimicking squamous cell carcinoma in a 40-year old smoker, who was also having
      speckeled leukoplakia on the buccal mucosa. The present case highlights the
      importance of histopathological diagnosis, as the treatment in latter case is
      aggressive, which is unnecessary if attempted with KA. Moreover, the present
      report provides an overview of such lesions, which could be encountered in
      clinical situations for which definitive diagnosis is of paramount importance
      before the starting of treatment plan.

PMID- 21965860
TI  - Skin as a marker of internal disease: a case of sarcoidosis.
AB  - A 52-year-old female presented to our out patient department with asymptomatic,
      hypopigmented lesions on the neck and back since 2 months. There was a history of
      taking antitubercular treatment for suspected pulmonary tuberculosis 2 years
      back. On blood investigations, the serum angiotensin converting enzyme levels
      were increased and the skin biopsy revealed a naked granuloma in the dermis. A
      diagnosis of systemic sarcoidosis was made and the patient was started on oral
      corticosteroids and Methotrexate, with clinical improvement.

PMID- 21965862
TI  - Omalizumab in treatment-resistant chronic spontaneous urticaria.

PMID- 21965861
TI  - Wickham striae: etiopathogenensis and clinical significance.

PMID- 21965863
TI  - Effect of 0.1% tacrolimus ointment in localized vitiligo: an open uncontrolled
      trial.

PMID- 21965864
TI  - Aquagenic pruritus: beneath water "lies".

PMID- 21965865
TI  - Hydroxyzine-induced acute generalized exanthematous pustulosis: an uncommon side
      effect of a common drug.

PMID- 21965866
TI  - D-penicillamine induced elastosis perforans serpiginosa mimicking acne keloidalis
      nuchae.

PMID- 21965867
TI  - Oligo-lesional eruptions rapidly following a herald plaque: abortive pityriasis
      rosea.

PMID- 21965868
TI  - A case of chronic myelogenous leukemia cutis: a rare presentation.

PMID- 21965869
TI  - Unilateral systematized linear porokeratosis: a report of a rare case.

PMID- 21965870
TI  - Paraneoplastic erythroderma complicated by hypothermia and hypothyroidism.

PMID- 21965871
TI  - Keratoacanthoma centrifugum marginatum: case report and review of literature.

PMID- 21965872
TI  - Dystrophic epidermolysis bullosa: report of a case with electron microscopic
      study.

PMID- 21965873
TI  - Using the ball-shaped attachment of a radiofrequency ablation device for
      preparation of recipient site in vitiligo surgery.

PMID- 21965874
TI  - Linear porokeratosis with follicular involvement.

PMID- 21965875
TI  - Liquid formulation of minoxidil versus its foam formulation.

PMID- 21965876
TI  - Problems of adolescence.

PMID- 21965877
TI  - Integration of mental health.

PMID- 21965879
TI  - Lithium and memory.

PMID- 21965878
TI  - Morals in medicine.

PMID- 21965880
TI  - Lithium prophylaxis in affective disorder.
AB  - Out of 108 patients on the rolls in the Lithium clinic, Madurai Medical College
      and Govt. Rajaji Hospital, Madurai, India, 47 patients suffering from affective
      disorders receiving lithium continuously for more than three years were analysed
      with a view to study the recurrences. Thirteen suffered no relapses while on
      lithium while nineteen experienced them while on lithium. Four were free from
      recurrences after lithium was withdrawn- Seven defaulted but suffered recurrences
      while in four the drug was withdrawn and in both the groups remission was
      achieved with re-administration of lithium. The study reveals that lithium
      besides averting the recurrences can reduce the frequency, number, duration,
      intensity of episodes and improve the amenability to drugs. Among the symptoms,
      suicidal ideas and behaviour and insight were found to be influenced favourably
      by lithium. Among the factors that help favourable response to lithium were a
      positive family history of affective disorder, in the first degree relatives and
      lesser frequency and number of episodes in the pre-lithium period. A reappraisal
      of the natural history of the illness is called for in the light of lithium
      prophylaxis of manic depressive psychosis.

PMID- 21965881
TI  - A bi-compartmentl model system for lithium kinetics in mania.
AB  - Lithium T1/2 has been determined from Lp decay. It is clear that calculation of a
      single T1/2 from Lp decay is essentially incorrect as the decay is not
      exponential. The same data points have been analysed on a kinetic model yielding
      3 different half lives too. The implication of the study is that the plasma and
      the erythrocyte systems undergo many local steady states instead of any global
      steady state. The rate of movement of Li (+) across plasma and erythrocyte
      undergoes fluctuations and may exhibit many more different half lives over a time
      period in either direction.

PMID- 21965882
TI  - Readmissions in a general hospital psychiatric unit - socio-economic and clinical
      correlates.

PMID- 21965883
TI  - Schizo affective psychoses-are they schixophrenic?

PMID- 21965884
TI  - Schizo-affective psychosis : is it an entity?
AB  - The nature of schizo-affective psychos is remains elusive even nearly 5 decades
      after its recognition. A brief review of the controversies in the nosological
      status of schizo-affective psychosis is presented and the observations made by
      the authors in 9 cases of schizo-effective psychosis are discussed.

PMID- 21965885
TI  - Reality of auditory hallucinations in schizophrenia.
AB  - 25 untreated urban living schizophrenics fulfilling the criteria of Feighner et
      al., having Schneiderian auditory hallucination were studied with the aim of
      examining the experienced reality of auditory hallucination and the influence on
      this reality of certain variables. It was found that the hallucinations were more
      real than unreal. Duration of illness, presence of anxiety prior to
      hallucination, reality testing ability, duration of each episode of
      hallucination, and socio-economic status scores influenced the reality
      negatively. The number of hallucinating days per mouth, position of voice outside
      sensory range, psychotocism scores, insight scores (higher scores for poorer
      insight) and duration of hallucination influenced the reality positively. The
      variables explained 72% of the variations in reality of hallucinations. Findings
      are discussed and suggestions for future studies are offered.

PMID- 21965886
TI  - Habituation of electro-dermal responses in tension-headache sufferers and non
      tension-headache controls.
AB  - Ten tension headache sufferers (TH) were compared with ten anxious neurotics (AN)
      and ten normal subjects in terms of electrodermal responses habituation (RH). TH
      sufferers showed less impaired RH than AN group, the normals showed least
      impairment. Moreover, it was evident that phasic elevation of electrodermal
      responses, rather than tonic measure, was a better indicator of individual
      differences between TH and AN groups.

PMID- 21965887
TI  - Personality and clinical manifestations of tension headache.
AB  - The personality dimensions and clinical manifestations of tension headache were
      studied and compared with neurotics and normals. The results showed that the
      experimental group differed significantly from normals. Persons with tension
      headache were introverted and scored highly on neuroticism. They did not differ
      from neurotics in personality and clinical manifestations except in relation to
      hysterical and obsessive features.

PMID- 21965888
TI  - A clinical study of hysteria in children and adolescents.

PMID- 21965889
TI  - Psychiatric aspects of hysterectomy.
AB  - A prospective psychiatric study of women undergoing hysterectomy conducted in
      Christian Medical College, Vellore, is described. About 20% of patients who had
      Hysterectomy developed depressive symptoms during the first year of follow up.
      Those who developed these symptoms had higher N score on Eysenck Personality
      Inventory and a higher M. R. Score on Cornell Medical Index before the operation
      when compared to those who did not develop psychiatric symptoms which suggests
      that the patients who have a higher score on Neuroticism are more prone to get
      psychiatric illness. It is emphasised that an attempt must be made to identify
      such patients who are more prone to get psychiatric disturbance in order to
      prevent or minimise these psychiatric disturbances. Prior consideration to these
      complications should be given before doing hysterectomy.

PMID- 21965890
TI  - Homosexuality : treatment by behaviour modification.
AB  - We present here the treatment of thirteen homosexuals by behaviour modification
      techniques. With classical electrical aversion and positive conditioning 8(61%)
      out of thirteen patients showed a change in orientation lasting on a six-month 1
      year follow up. A marriageable age and indirect social pressures were positively
      correlated with improvement whereas the presence of a steady homosexual partner
      and habitual passive anal intercourse indicated a poor response. The techniques,
      the assessments, the onset and course of improvement and complications arc
      discussed. Our results and techniques are compared with those of other workers.

PMID- 21965891
TI  - Family history of mental illness as a factor in relapse and non relapse of
      discharged functional psychotics.
AB  - 842 patients suffering from the functional psychoses were followed up for 4-6
      years after their discharge from Mental Hospital, Agra during January 1969 to
      December. 1970 in order to study the recurrence of the disease in them. This was
      done by reviewing the case history sheets of outpatient and inpatient departments
      of mental hospital, Agra and also by the personal correspondence wherever
      necessary. Out of these 824 patients, 336 were found to have relapsed. This study
      reveals the effect of family environment on the prognosis of functional
      psychoses. The relapse of functional psychoses was not found to be related to the
      genetic loading.

PMID- 21965892
TI  - Personality dimensions of criminals and mentally-ill-criminals.
AB  - Sixty male criminals selected randomly from the Central Prison of Madras and
      twenty mentally ill criminals from the Institute of Mental Health, Madras, were
      administered E.P.Q. and compared with sixty normals. The results show that
      criminals scored significantly nigh on extroversion, psychoticism and
      neuroticism. The mentally ill criminals scored significantly on psychoticism
      compared to normals. Criminals and mentally ill criminals do not differ
      significantly on any of the scales of E.P.Q.

PMID- 21965893
TI  - Idiopathic torsion dystonia with schizophrenia in first degree relatives : a case
      report.
AB  - A patient having two schizophrenic brothers developed simple writer's cramp at
      the age of 20 years. Three years later she developed irregular and unusual
      movements which was diagnosed and treated as hysteria until she had contractures
      in the right hand. EMG studies revealed abnormalities suggestive of torsion
      dystonia. The association of schizophrenia in the first degree relatives and the
      differential responses to haloperidol in this case of torsion dystonia has been
      discussed.

PMID- 21965894
TI  - Trichotillomania-a brief review and case report.

PMID- 21965895
TI  - A need for marriage counselling.

PMID- 21965896
TI  - Guilt in India (social, cultural and psychological perspectives).

PMID- 21965897
TI  - Linguistic competence and psychopathology : a cross-cultural model.
AB  - The present paper discusses the possible role of linguistic competence in
      determining the manifest psychopathology of schizophrenia. It is hypothesised
      that the linguistic competence may be a significant determinant of
      psychopathology and may explain the differences in the manifest signs and
      symptoms, course and prognosis between the various sub-types of schizophrenia and
      may explain the cross-cultural differences in the phenomenology and outcome of
      the disease. It is proposed that research should be undertaken in measurement to
      linguistic differences to test out the above hypotheses.

PMID- 21965898
TI  - Psychiatry of criminal behaviour.

PMID- 21965899
TI  - A follow up study of hysteria.
AB  - The present study undertook to examine the outcome of a group of cases who were
      diagnosed as hysteria, six or more years ago in a general hospital psychiatric
      unit and correlate various clinical factors with good or bad outcome. Of the 81
      cases selected for the study, 57 (67%) could be located and followed up after a
      gap of 6-8 years. Majority of the cases (74%) had either no symptoms or symptoms
      less than before at the time of the follow up. In only 3 cases, there was
      evidence of an underlying organic illness which seemed to have been missed at the
      initial assessment. A new sub-classification of hysteria with glossary of terms
      used for this study is presented for future research work.

PMID- 21965900
TI  - A comparative study of attitudes of the key relatives towards 'schizophrenic
      patients' and 'patients of disturbed family'.
AB  - Forty six key relatives of 'Schizophrenic Patients' who were hospitalised in
      Department of Psychiatry, K. G's, Medical College, Lucknow were administered
      'Attitude Questionnaire' which covered five variables : Number of critical
      comments about someone else in the home ; Hostility; Dissatisfaction; Warmth and
      Emotional Involvement. Forty one key relatives of 'Disturbed Family's Patients'
      matched for sex and residence, were assessed on similar parameters. There was
      significant difference only in the area of 'Dissatisfaction'.

PMID- 21965901
TI  - Mental health delivery through rural primary care-development and evaluation of a
      training programme.
AB  - There is a growing consensus of opinion (WHO 1975) that in developing countries,
      doctors and para-medical staff of the existing health care cadres should, after a
      short course of problem oriented training, deliver basic mental health care. This
      paper describes the development and evaluation of such a training programme.

PMID- 21965902
TI  - The personality factors of the parent of (male and female) schizophrenics.
AB  - It was hypothesised that there exists significant difference between the parents
      of male and of female schizophrenics and those of the corresponding control group
      in the personality factors. The experimental group consisted of 62 pairs of
      parents of 62 male and 38 pairs of parents of 38 female schizophrenics. A control
      group of 100 pairs of parents of mentally and physically healthy off-springs were
      taken. Subjects were matched for intelligence level, age level, sex, level of
      education, religion and per capita income and all of them were free from mental
      illness at any time during their life. The Bengali version of Cattail's 16 PF (C
      Form) (excluding Factor B) was used. The parents of schizophrenics were found to
      be significantly different from the corresponding control group in certain
      personality factors. The results substantiate the hypotheses.

PMID- 21965904
TI  - Socio demographic variables in unipolar and bipolar illness.

PMID- 21965903
TI  - The child-rearing attitudes of the parents of (male and female) schizophrenics.
AB  - It was hypothesised that there exists significant difference between the parents
      of male and of female schizophrenics and those of the corresponding control
      group, in the child-rearing attitudes. The experimental group consisted of the 62
      pairs of parents of 62 male and 38 pairs of parents of 38 female schizophrenics.
      A control group of 100 pairs of parents of mentally and physically healthy off
      springs were taken. Subjects were matched for intelligence, age, sex, level of
      education, religion and per capita income and all of them were free from mental
      illness at any time during their life. The Bengali version of PARI for fathers
      were used. The results were consistent with the hypotheses. Certain child-rearing
      attitudes of the parents of schizophrenics were found which were significantly
      different from the corresponding control groups.

PMID- 21965905
TI  - Physiological and psychological aspects of anxiety in psychiatric patients and
      normal subjects.
AB  - Physiological (Skin conductance) and Psychological (State-trait anxiety) measures
      of anxiety were employed to assess the level of anxiety in 10 anxious neurotics,
      10 schizophrenics and 10 normal subjects. Both the Physiological and
      Psychological measures were sensitive in detecting the level of anxiety in
      normals and patients. But interrelationships between these two measures were very
      poor.

PMID- 21965906
TI  - Relationship of psychoticism with certain socio-economic variables.
AB  - A psychoticism questionnaire developed by the authors (Arora & Varma, 1980 a, b)
      was administered to 100 psychotics, 100 neurotics, 100 relatives of psychotics,
      and 100 normals. Relationship of P-score with six socioeconomic variables, i.e.,
      age, sex, education, occupation, religion and urban, rural background was
      studied. P-score was found to be higher in younger age group (15-24 years) in
      each of the four clinical groups but was significantly low in psychoitics and
      their relatives. No sex differences were observed regarding P-score. Significant
      inverse relationship between P-score and education and occupational status was
      found only for the normal groups. No significant difference was seen in
      psychoticism score between the two religious groups-Hindus and Sikhs. Those from
      rural background had higher P-score as compared to those from urban background,
      but the differences did not reach statistical significance.

PMID- 21965907
TI  - Serum potassium changes with e.C.T.
AB  - Serum potassium changes with direct E.C.T. and with modified E.C.T., given under
      three anaesthetic (thiopentone, diazepam and propanidid) and relaxant
      (suxamethonium) combinations were studied in 25 patients. Ten patients each,
      undergoing minor surgical procedures, acted as controls for these three
      combinations. Modified E.C.T. caused a rise in scram potassium, which, being
      highest at 3 minutes, was sustained well beyond 10 minutes. Direct E.C.T. caused
      maximum rise within one minute which, however, came down rapidly. The rise
      following modified E.C.T. was one and half times more compared to that occurring
      in controls given only drugs but not E.C.T., in all the three anaesthetic
      relaxant combinations. The rise from pre-induction level was maximum following
      diazepam and minimum with propanidid, thiopentone falling in between. The rise
      from pre-relaxant level, on the other hand, was maximum with thiopentone and
      minimum with propanidid.

PMID- 21965908
TI  - The repertory grid interview of a depressed patient.
AB  - The construct system of a patient of Depression is investigated with the Rank
      Order Repertory Grid Technique, using principal component analysis to analyse the
      grid matrix. The investigation helps test clinical judgments and hypotheses
      concerning the patient and also suggests new directions for further clinical
      enquiry. This case study demonstrates how the grid technique can make possible a
      more comprehensive understanding of the cognitive processes of the patient.

PMID- 21965909
TI  - Male homosexuality : a psychiatric study of thirteen cases.
AB  - 13 male homosexuals who approached us for treatment were studied. They came from
      unusual family back-grounds, had early homosexual experiences which were repeated
      and later became pleasurable. They showed a variety of homoerotic activity.
      Belonging to a marriageable age group, the social disadvantages of their
      homosexual behaviour prompted them to seek treatment. It was observed that early
      childhood experiences are important in the causation of homosexuality, early
      channelization of the sexual drive or to objects of the same sex by homosexual
      seduction and subsequent habituation also played an important part.

PMID- 21965910
TI  - Juvenile manic depressive psychosis - report of 3 cases.
AB  - Three patients, one female and two males, with bipolar affective psychosis
      beginning at the ages of twelve, nine and fourteen years, are described. The
      symptomatology in all the three patients was similar to that of the adult manic
      depressive psychosis and the response to lithium was good.

PMID- 21965911
TI  - A case of pykno-dysostosis with psychosis.
AB  - A rare case report of association of affective psychosis with pyknodysostosis is
      discussed.

PMID- 21965912
TI  - Koro : a peculiar anxiety neurosis (a case report).

PMID- 21965913
TI  - Geriatric psychiatry-an upcoming challenge.

PMID- 21965914
TI  - Theoretical issue of endogenous psychoses.

PMID- 21965915
TI  - Present state of psychotherapy in India.

PMID- 21965916
TI  - Certain aspects of drug abuse-an epidemiological study.
AB  - Certain aspects of drug abuse have been presented from the pooled data of
      psychiatric epidemiological surveys conducted by the authors in the rural areas
      of West Bengal.

PMID- 21965917
TI  - Indigenous therapy in practice of psychiatry in India.

PMID- 21965918
TI  - Extension of mental health service through psychiatric camps : a new approach.
AB  - Psychiatric camps in the manner they are usually conducted serve no useful
      purpose in the long run, except to identify cases and to increase people's
      awareness about mental illnesses. The main drawback is poor follow up of the
      cases detected.To overcome these drawbacks and to make these camps more useful in
      delivering mental health services to the community, a new approach is being
      worked out. Screening and selection of the patients for the camp by the local
      doctors with the help of symptom check-list, a good propaganda well in advance
      incorporating the cardinal symptoms through mass media, training of the local
      doctors to gain basic skills and knowledge to manage cases during follow up,
      periodic visits by the psychiatrists to help these doctors in this job for some
      time, mental health exhibition during the camp were some of the strategies
      adopted in Kollegal Neuropsychiatric camp by community psychiatry unit of
      NIMHANS.It was a three days' camp. 312 cases were registered after screening.
      Only 6.7% cases were non-psychiatric. 30% epileptics, 30% neurotics, 12%
      Headache, 9% MR, 9% neurological cases, 5% psychoses. 25 doctors participated in
      training programme and camp patients were allotted to them for follow up. Monthly
      follow up is in progress. Findings and experiences are discussed.

PMID- 21965919
TI  - Evaluation of disulfiram in the treatment of alcoholism.
AB  - Seventy five male patients with the diagnosis of alcohol dependence syndrome were
      given disulfiram and an alcohol challenge was administered to all of them. They
      were kept on maintenance dose of the drug and followed up for six months, note
      being made of their improvement on several parameters, viz. the number of
      drinking episodes, the sevarity of reaction suffered, the side effects
      experienced etc. Twenty one patients were considered as drop outs and four were
      abstainent without the aid of the drug. 54 % of the fifty patients who continued
      taking the drug showed good to moderate improvement. 42% had one or more drinking
      episode while consuming the tablets. Older patients, and those brought by
      relatives and friends did better than the others. Results are discussed.

PMID- 21965920
TI  - Dermatolglyphic studies in schizophrenia : a review.
AB  - Dermatoglyphic studies Carried out in Schizophrenia have been evaluated and
      critically examined. Methodological errors existing in the previous studies have
      been pointed out and some guidelines for methodological refinements suggested and
      a dermatoglyphic corsensus index for diagnosis has been evolved. The
      heterogeneous nature of schizophrenia, being a group of syndromes, has been
      unanimously accepted, therefore, each category should be studied separately.
      Further scope of this potentially fruitful area has been discussed.

PMID- 21965921
TI  - Gerospsychiatric morbidity survey in a semi-urban area near madurai.
AB  - Tiruppuvanam, with a population of 15,668 a semi-urban area near Madurai was
      chosen for a door to door survey to assess the psychiatric and physical morbidity
      in all those aged 60 and above. There were 686, in this age group. The socio
      economic status, family structure, social integration, occupation, literacy,
      physical illness and handicaps in the total population were assessed and compared
      with the psychiatrically morbid group. The prevalence of psychiatric morbidity
      was estimated at 89/1000. 48.84% suffered from physical morbidity. 57% of the
      psychiatric group suffered physical morbidity and 85% from sensory handicaps. The
      findings indicated that lack of social integration rather than social isolation,
      and lack of occupation were significantly related to psychiatric morbidity. The
      type of family structure did not relate to the degree of social integration.
      Depressive illness contributed to 67% of total psychiatric morbidity, some
      intervention measures are suggested.

PMID- 21965922
TI  - Socio-cultural factors in late onset depression.
AB  - An epidemiological survey of subjects aged over 50 in a sub urban area of India
      was carried out. 406 subjects aged over 50were examined by making house visits.
      13 were diagnosed as suffering from organic psychoses, 3 from schioephrenia, 98
      from depression and 28 from other functional disorder. Depression was the
      commonest diagnosis made. 24.1% of the subjects aged over 50 in the community
      were found to suffer from depression. Female sex, low social class, widowed
      state, unemployed condition, low educational level, nuclear family, living alone
      and high incidence of physical illness was found associated with depression. The
      significance of these factors, Hindu philosophy and Indian family system is
      discussed.

PMID- 21965923
TI  - Physical disabilities in late onset depression in the community.
AB  - A community survey of subjects aged over 50 was carried out. 406 subjects were
      randomly selected and examined. 264 were found normal, 98 subjects were found to
      suffer from depression of late onset type. Detailed enquiry was made about the
      physical health in all subjects using a specially drawn 42 item somatic
      discomfort inventory. Each symptom was graded as mild, moderate and
      severe.Similarly sensory disabilities such as dimness of vision and hearing
      defects were classified into mild, moderate and marked.It was found that physical
      illness, sensory deficit, chronic ailment, recent deterioration in health,
      restriction of movement and difficulties in self care were more frequently
      observed in late onset depressives in the community than in normal
      subjects.Further, using I.B.M. computer, Principal component analysis was done to
      examine the correlation of physical illness variables, socio-economic variables,
      personality variables, variables or emotional attitudes and of the occurrence of
      depression. Physical illness variables had high loadings in Factor I-General
      illness factor and Factor II-Isolation factor.Thus it is concluded that physical
      disabilities had significant association with depression of late onset type and
      the physical illness limiting the movement of the subject combined with
      environmental conditions led to the feeling of loneliness and depression.

PMID- 21965924
TI  - Non-organic dyspepsia : a controlled psychometric study.
AB  - Fifty-two non-organic dyspeptics, 40 organic dyspeptics and 40 age-sex matched
      normal controls administered the Hindi version of Middlesex Health Questionnaire
      and the Amritsar Depressive Inventory. The non-organic cases scored significantly
      higher compared to the other two groups on the both the tests and on all the sub
      scales of the MHQ. Cases with irritable bowel syndrome scored maximum on
      obsessive subscale and the remaining sub-groups (hypochondriasis, depression and
      hysterical neurosis) on the somatic subscale. The mean total score on MHQ was
      maximum in hysteria and minimum in irritable bowel syndrome.

PMID- 21965925
TI  - A study on perception of facial expressions of emotions in depression.
AB  - The study was designed with a view to examine the relationship between perception
      of facial affects and psychopathology. Forty normal and twenty depressive
      subjects were asked to recognize the facial emotions provided and to discriminate
      the emotional tone in terms of intensity of expression while presented in pairs.
      A pair comparison solution indicate that the depressives were highly evaluative
      in the effect of sadness and less evaluative in happiness, in comparison to
      normals.

PMID- 21965926
TI  - Serum acetylcholinesterase activity in psychiatric patients.
AB  - Serum acetylcholinesterase activity was measured in hospitalized 30 schizophrenic
      and 30 depressive patients. It was observed that the enzyme activity was
      significantly higher in depressive patient than controls (Comprising of 20
      surgical subjects). An increase in activity with the duration of illness was also
      noted in such patients. In contrast, schizophrenics did not show any significant
      increase except a little increase along with the number of episodes on comparison
      with control subjects. In view of the cholinergic predominance in depression it
      is suggested that increased serum cholinesterase activity in the aforementioned
      disorder may be due to a biochemical defence against the stress of higher
      acetylcholine content in the body fluids.

PMID- 21965927
TI  - An epidemic of possession in a school of South India.

PMID- 21965928
TI  - A study of behaviour during auditory hallucinations in schizophrenics.
AB  - Thirty untreated urban living Schizophrenics fulfilling the criteria of Feigher
      et al. (1972) and having Schneiderian hallucinations were studied with the aim of
      examining the relation of certain variables to their behaviour during auditory
      hallucinations. For those whose behaviour had no direction, the voices were less
      real in comparison to those with positive or negative direction. For those with
      negative direction in behaviour, voice were positioned more outside than within
      sensory range and the individual episodes of hallucination were of longer
      duration. The voices were more real for those who had emotional experience
      without physical activity and those without emotions of physical activity.

PMID- 21965929
TI  - Craniopharyngioma presenting as 'mania'-case report.
AB  - We are reporting a case of craniopharyngioma presenting with features of mania.
      To our knowledge, this is the first reported case of craniopharyngioma with
      presenting features of mania- The patient is a six years old child with history
      of maniac behaviour of six months duration. There is no significant family
      history. During the course in the hospital he was found to be having
      craniopharyngioma. The patient recovered completely following the surgical
      intervention without any aid of antipsychotics.

PMID- 21965930
TI  - Mental health bill 1981 : a ray of hope.

PMID- 21965931
TI  - Hindi version of present state examination : problems of translation and
      application in Indian setting.
AB  - The present State Examination (PSE) schedule is a widely used instrument to
      record mental status of adult neurotic and functional psychotic patients. It has
      140 items based in a semi-structured interview. Each item is rated on ordinal
      scale. Ratings are based on clinical judgement for which comprehensive glossary
      is provided. PSE has been used in several international collaborative studies
      which show that this standardised instrument can be used reliably. The
      experiences gained in using the Hindi version of the PSE have been highlighted.
      It has been observed that although there are some limitations, the PSE as a
      research instrument can be used reliably in the Indian setting. There is a need
      to gain experience in using the PSE in other Indian languages.

PMID- 21965932
TI  - Psychotherapy for the economically less privileged classes (with special
      reference to India).

PMID- 21965933
TI  - Life event research : a review of methodology (with special reference to India).
AB  - In spite of extensive work having been done on the correlation between
      significant life events and development of physical as well as psychiatric
      illnesses, major controversies remain on the methodological issues involved. The
      present paper deals with some of these issues, e.g., selection of events and
      formation of event lists, severity rating of individual events, summation of
      event scores, reliability of reporting and provision of adequate control groups.
      Different modes of categorization of events are discussed. Need for caution
      regarding straight correlation of experienced events with illness has been
      pointed out. Special emphasis has been given to methodological modifications
      necessary for life event research in India. These include the issue of culture
      specificity of events and relatively prolonged stresses, reliability testing from
      a family member and use of semi-structured interview method in preference to
      paper and pencil questionnaires. Suggestions are offered for better controlled
      and methodologically superior studies on life events in India.

PMID- 21965934
TI  - Pineal response to lithium.

PMID- 21965935
TI  - Memory in depression.
AB  - Out of 88 cases of depression, admitted in Department of Psychiatry, K.G's.
      Medical College, Lucknow, 33 cases fulfilling the inclusion criteria were
      assessed for severity of depression and memory performance and were compared with
      memory scores of normal healthy controls. After treatment with drugs, improved
      depressives served as their own controls also. Memory scores of depressives were
      found to be significantly poor than those of controls and of their own after
      recovery. Depression was found to be negatively correlated with memory. Mental
      control sub-function of memory was most sensitive for depression. Probable
      mechanism of memory disturbances were discussed.

PMID- 21965936
TI  - Long stay patients in a state mental hospital.
AB  - A study of the long stay patients in a state mental hospital on 30th June 1980
      revealed that 70 per cent of the total 1,434, i.e. 1015 had spent more than two
      years continuously; most of them are chronic schizophrenics, admitted by the
      police, lacking social support. The need for rehabilitating them both within and
      outside the hospital is stressed.

PMID- 21965937
TI  - Hysterical psychosis.
AB  - Clinical features of 88 patients diagnosed as having hysterical psychosis are
      analysed and compared with those of an equal number of catatoaic schizophrenics
      and conversion reaction. Hysterical psychosis is characterised by acute onset.
      often following the occurence of an emotionally disturbing event, absence of any
      characteristic thought disturbance, and emotio.ial volatility. Prognosis is good.
      Even though physical methods of treatment like drugs and E.G.T. had to be used in
      many patients to control the acute disturbance, psychotherapy and family therapy
      were found to be essential for the abatement of presenting symptoms as well as
      prevention of their recurrences.

PMID- 21965938
TI  - A study of patients attending emergency out-patient services of a large teaching
      institution.
AB  - Authors have studied the pattern of psychiatric morbidity at the general
      emergency out-patient services and at the emergency psychiatric services being
      run concurrently at a large teaching institution. The percentage of psychotics
      was observed to be maximum at emergency psychiatric services. Non-psychiatric
      medical officers were observed to deal with non-psychotic psychiatric emergencies
      themselves rather than referring them to emergency psychiatric services.

PMID- 21965939
TI  - A study of emergency psychiatric referrals in a teaching general hospital.
AB  - The socio-demographic and clinical characteristics of one hundred consecutive
      referrals from emergency O.P.D. of a teaching general hospital were studied. The
      referral rate was 5.4%. The source, reason and purpose of the referrals were
      studied. Half of the patients had presented with somatic symptoms. Altered
      sensorium, suicidal attempt and excitements together constituted one third of all
      emergency referrals. The diagnosis of neurosis was given in half of the patients
      and one third of all patients were labelled as suffering from hysterical
      neurosis. The nature of the presenting complaints and psychiatric diagnoses were
      comparable to that of the other studies.

PMID- 21965940
TI  - The koro epidemic in lower assam.
AB  - This paper deals with the recent epidemic of kore which occurred in four
      districts of Assam lasting from later part of June, 1982 to middle of September,
      1982, In a survey of 83 cases including 19 females seen by the Psychiatry
      department of Gauhati Medical College-various socio-economic-Cultural factors and
      clinical symptomatology are analysed. The significant findings are : Koro
      affected mostly young males below 30 years belonging to Hindu Assamese community,
      coming from middle class families, suffering preponderantly from genital
      symptoms. Koro attacks mostly occurred during the night when the patients are
      indoor. Exposure to hearsay and/or witnessing a koro case is an important
      predeterminant of the episode of illness. In the series, marriage educational
      status and skill in occupation did not seem to offer any immunity to the victims.
      Relapses are few. The epidemic subsided without any fatality after massive
      reassurance to the public through mass media.

PMID- 21965941
TI  - A study of patients attending mehandipur balaji temple : psychiatric and
      psychodynamic aspects.
AB  - A sample of 100 patients were selected randomly from 10 dharamshalas who
      qualified the diagnosis of neuroses and developed "trance". They were subjected
      to tests of suggestability, intelligence, guilt, hostility and neuroticism.
      Patients with "trance" were significantly more suggestible and expressed more
      hostility and guilt as compared to those who did not develop trance. Significant
      differences were found on I.Q, and level of neuroticism in trance and non-trance
      patients as well. No significant differences were observed on suggestibility,
      I.Q., hostility, guilt and level of neuroticism in patients who developed trance
      either early or delayed.Hysterial patients with trance and non-hysterical
      patients with trance failed to differ on suggestibility, I.Q. and projective
      measures of hostility and guilt. The significance of these factors in the
      development of trance and cure of psychoneurotic patients in context of our
      cultural background and faith healing practices has been discussed.

PMID- 21965942
TI  - Depressive symptoms-an intercentre comparison.
AB  - 45 Psychotic Depressives from PGI, Chandigarh have been compared with 90
      Psychotic Depressives from Madurai Centre on 40 symptoms using SADD schedule.
      Differences in the symptomatology have been highlightened.

PMID- 21965943
TI  - Post partum psychiatric syndromes-an analysis of 100 consecutive cases.
AB  - 100 consecutive out patients with onset of Psychiatric illness within 40 days of
      child birth were studied by using Indian Psychiatric Interview Schedule and a
      specially designed Proforma. It was found that post partum psychiatric syndromes
      occurred most frequently in patients less than 25 years of age. Stress of
      Physical illness was present in a considerably high number of patients (74%). In
      66% the Psychiatric illness was associated with first child birth and risk of
      Puerperal Psychosis in subsequent deliveries was found to be 32%.; Onset of
      illness is seen most frequently (85% cases) within 3 weeks of child birth. The
      Diagnostic breakup showed Schizophrenic reactions (68%) affective disorders (25%)
      and neurotic reactions (7%). Findings have been discussed.

PMID- 21965944
TI  - Clonidine in opiate detoxification.

PMID- 21965945
TI  - Detection of alcoholism among psychiatric inpatients.
AB  - One hundred and eighty four consecutive admissions to male psychiatric open and
      closed wards were examined for evidence of alcoholism. Michigan Alcoholism
      Screening Test (MAST) was used for this purpose. The present study shows a
      prevalence rate of alcohol users to be 41.3 per cent. Nineteen percent could be
      called alcoholic. MAST correlated well with Spitzer's RDG criteria for
      alcoholism. The family history of non-users was significantly different from that
      of the alcohol users. The findings are discussed in the light of existing
      literature both in India and in the West.

PMID- 21965947
TI  - Trichotillomania in association with psychosis-a case report.

PMID- 21965946
TI  - Fantasy and feminity-a pattern in sex deviation.

PMID- 21965948
TI  - Mitral valve prolapse syndrome and its association with anxiety and panic States.
AB  - Mitral Valve Prolapse Syndrome is one of the most frequent cardiac valvular
      abnormalities in general population. Mostly the patients remain asymptomatic but
      a few may suffer from hyperadrenergic panic states, similar to anxiety attacks.
      In psychiatric practice, a number of physicians have come across this finding
      during the recent past. Present article deals with two such case illustrations.

PMID- 21965949
TI  - Need for growth of forensic psychiatry.

PMID- 21965950
TI  - Genetic research in psychiatry.

PMID- 21965951
TI  - A search into the mystery of schizophrenia.

PMID- 21965952
TI  - Temporal lobe epilepsy : phenomenology and psycho-sexul manifestations.

PMID- 21965953
TI  - Mental health services in kenya.

PMID- 21965954
TI  - Rapid increase of heroin dependence in delhi: some initial observations.
AB  - The present paper documents and discusses the rapid increase in the problem of
      heroin dependence in the city of Delhi in the recent years. Initial observations
      on patients with heroin dependence attending the Deaddiction Clinic of a large
      general hospital are described with difficulties encountered in the clinical
      management of these patients. It is suggested that sustained efforts be made to
      control this problem because heroin is likely to give rise to medical and social
      consequences of serious nature in the near future.

PMID- 21965955
TI  - Personality pattern of parents of mentally retarded children.
AB  - Parents of fifty mentally retarded children were studied for their personality
      pattern with the help of Middlesex Hospital Questionnaire. In fathers and mothers
      separately, none of the personality traits were observed to vary at statistically
      significant level in relation to the degree of retardation in their child, but
      both the parents of mildly retarded children obtained higher score on scale of
      anxiety, phobia and depression. Analysis of different factors when compared for
      fathers and mothers together, revealed a higher degree of neurotic traits in
      mothers.

PMID- 21965956
TI  - Cognitive dysfunction in depression.
AB  - Thirty patients of primary depression were assessed for their cognitive functions
      initially in the depressed state and on complete recovery. The results indicate
      presence of definite cognitive impairment during the depressed state (as measured
      by the Bhatia's Battery test and PGI memory scale) which is restored to normal
      after recovery from depression. The intensity of depression as indicated by the
      Hamilton Rating Scale for depression was directly related to the degree of
      cognitive impairment.

PMID- 21965957
TI  - Drug abuse in India: an overview with special reference to cannabis.
AB  - The Indian literature related to drug abuse in general and Cannabis in particular
      has been reviewed and possible implications discussed. In this regard to solve
      the existing controversy, 50 pure chronic cannabis users were evaluated for their
      physical, mental, cognitive and socio economic functions and the results were
      compared with a matched control group. Results of this study did not reveal any
      impairment in these areas It is concluded that cannabis, in India, may not be as
      much injurious to health as has often been mentioned in Western Countries. Future
      areas of research have been suggested.

PMID- 21965958
TI  - Effect of lithium carbonate on renal and extra-renal functions of rats.
AB  - Effect of high doses of lithium carbonate (40 rag/Kg.i.p. and p.o.) and lithium
      chloride (40 mg/Kg.i.p.) on renal and extra-renal functions were studied in
      normal male Charles Foster Strain of rats. Insignificant effect on urine output,
      creatinine clerance, sodium, potassium and lithium excretion was observed with
      these salts. Antidiuretic hormone levels were also not effected. However lithium
      clearance was significantly raised in both groups with lithium carbonate and with
      lithium chloride treated rats. Lithium carbonate and lithium chloride had failed
      to produce nephrogenic polyuric syndrome in this strain of rats.

PMID- 21965959
TI  - Obsessive compulsive neurosis: treatment of 28 cases by behaviour therapy.
AB  - Twenty-eight cases of obsessive compulsive neurosis were treated with a behaviour
      therapy package and good results were obtained in 15 (53.6%). Relaxation, thought
      stopping, implosion, modelling, response prevention, electrical aversion and
      positive reinforcement wei; the techniques employed. Chronicity, previous
      treatments, follow-up data, drop-outs and the use of behaviour therapy in our
      setting are discussed in this paper.

PMID- 21965960
TI  - Dhat syndrome: the phenomenology of a culture bound sex neurosis of the orient.
AB  - Indian Dhat syndrome which is symptom complex most commonly seen in younger group
      of patients in between 16 to 23 years of age. These patients present with whitish
      discharge with urine (patients believe it to be semen). This is associated most
      commonly with impotency, marked anxiety, general weakness, premature ejaculations
      and hypochondriasis. All the patients were either from low or average
      socioeconomic status. Majority of the patients attributed masturbation as a
      causative factor for this problem.

PMID- 21965961
TI  - The role of a liaison psychiatrist in a neonatal intensive care unit.

PMID- 21965962
TI  - A behavioural approach to the treatment of writer's cramp.
AB  - In (perhaps) one of the largest series, treatment of 30 cases of writer's cramp
      by behaviour therapy alone, has been studied over a period of 5 years. The
      therapy techniques used were (i) relaxation therapy and retraining (ii)
      relaxation therapy, retraining and systematic desenetization. The outcome of both
      the techniques are very encouraging and show definite improvement in all cases.
      Various factors responsible for degree of improvement and the duration of
      treatment are discussed.

PMID- 21965963
TI  - Multidisciplinary rehabilitation of the mental retard.

PMID- 21965964
TI  - Lorazepam dependence : a case report.

PMID- 21965966
TI  - Health and behaviour.

PMID- 21965965
TI  - Catatonia associated with uraemic encephalopathy.
AB  - Catatonia is oily a clinical diagnosis with a variety of possible aetiological
      conditions. Among the many neuropsychiatric disorders in renal failure, catatonia
      is one which has not been established well. The authors report two cases in which
      despite strong evidence for primary psychiatric disorder, on investigation the
      catatonic state was found to be associated with ureaemic encephalopathy.

PMID- 21965967
TI  - Unipolar and bipolar depressions-a review.
AB  - The paper discusses the emergence of the concept of polarity out of the rubric of
      manic depressive illness. The polar types are defined and changes in polarity,
      frequency and similarities and the differences between them are discussed. The
      author ventures to suggest that a change in the polarity viz., occurrence of
      mania in depressive or of depressive episodes in mania to be designated "LAP
      Phenomenon" after Leonhard, Angst and Perris who have been mainly responsible for
      the concept.

PMID- 21965968
TI  - Presumptive stressful life events scale (psles) - a new stressful life events
      scale for use in India.
AB  - Using an open ended question along with Holme's and Rahe's Social Readjustment
      Rating Schedule on a sample of two hundred adult subjects, a suitable scale of
      stressful life events experienced by the Indian population was constructed and
      standardized for two time spaces, that is, last one year and life time. Analysis
      of various demographic variables for this population revealed no differences on
      this scale for age, marital state, education and occupation. However, marked sex
      differences in the perceived stressfulness were observed for three of the items.
      The scale items were further divided into desirable, undesirable and ambiguous
      and also into personal and impersonal Categories. Statistically significant
      difference were observed between the desirable and undesirable items, the latter
      being perceived as more stressful. Norms for total number of life events
      experienced as well as the presumptive stress score were established for each
      event for this population. The frequency of occurrence of each event in our
      population was also obtained. It was Calculated that individuals in our society
      are likely to experience an average of two stressful life events in the past one
      year and ten events in a life time without suffering any adverse physical or
      psychological disturbance. The scale is simple to administer to literate and
      illiterate subjects.

PMID- 21965969
TI  - Behaviour charateristics of the mentally retarted in a state mental hospital-a
      comparative study.
AB  - 30 institutionalised severely subnormal (SSN) subjects and 30 matched severely
      subnormal individuals attending the outpatient services of the Institute of
      Mental Health, Madras were evaluated for their behaviour characteristics using a
      schedule containing two scales,the social and physical incapacity (SPI) scale and
      the speech, self help and literacy (SSL) scale. Destructive behaviour, self
      injury, overall poor speech, self help and literacy ability, overall social and
      physical incapacity, poor speech ability, poor speech comprehensibility, poor
      self help and poor literacy were the discriminating factors much more common for
      the institutionalised subjects than for the outpatient individuals. The
      usefulness of this informations in the planning and implementation of services
      for the institutionalised mentally retarded is discussed.

PMID- 21965970
TI  - A comparative study of efficacy of emg bio-feedback and progressive muscular
      relaxation in tension headache.
AB  - The aim of the present study was to find out efficacy of frontalis EMG
      Biofeedback therapy, deep muscular relaxation therapy and compare the efficacy of
      both in cases of tension headache. During two week basal-data recording period
      all patients were taught deep muscular relaxation by Jacobson's technique.
      Simultaneously patients were instructed to keep headache diary. Headache diary
      yielded three different parameters a) number of headache-free days per week, b)
      peak headache intensity (or each week and c) average daily headache activity
      score per week. These parameters were used to find out therapeutic efficacy of
      each treatment. Patients were randomly divided in two groups. EMG Biofeedback
      group was given frontalis EMG feedback through EMG J 33 muscle trainer of Cyborg
      Corporation (U.S.A.). Patients in each group were given 20 sessions (two sessions
      per week); each session lasting 30 minutes. Patients were instructed to practice
      at least one 30 minute session of relaxation at home. The data were subjected to
      statistical calculation. The results indicate that frontalis EMG Biofeedback
      therapy and deep muscle relaxation therapy are significantly effective in cases
      of tension headache. Both treatments are equally effective. The findings are
      discussed in relation to Indian situation.

PMID- 21965971
TI  - Alcohol and drug abuse among internees.
AB  - The study was designed to assess the various factors pertaining to alcohol and
      drug abuse among internees with the help of the youth survey questionnaire
      developed by the WHO. 22.67% of the males indulged in alcohol abuse atleast once
      a month. Correspondingly cannabis was abused by 9.33% of the boys which is the
      most commonly abased drug of addiction, followed by sedatives and
      tranquilizers.The commonest explanation is offered for the non medical drug abuse
      were, to be sociable, for enjoyment, curiosity and relief of psychological
      stress. Friends have been the main source of introduction. Most of them reported
      that it was easy to obtain the drugs like marijuana and amphetamines.

PMID- 21965972
TI  - Psychological study of inmates of a childrens home with special reference to
      their intelligence and aggressive behaviour.
AB  - Sixty two inmates of a children's home of Lucknow City were examined by using
      Hindi Adaptation of Stanford Binet Intelligence Scale-Form LM (1960) and a five
      point rating scale for aggression. A high proportion (69.4%) of the inmates had
      one or other psychiatric problem. Mild mental retardation (I.Q. 50-70) was most
      common (41.9%). Intellectual level was correlated with present age, duration of
      stay and age at entry. Significant correlation was found between Intellectual
      level and present age, as well as duration of stay. Nearly 39% inmates showed
      aggressive behaviour. Aggressive behaviour was also correlated with present age,
      duration of stay, age at entry and psychiatric illness. The children suffering
      from emotional problems (such as unsocialised disturbance of conduct, adjustment
      reaction, nail biting, enuresis etc.) showed significantly more aggression than
      healthy children. Though no significant difference was fourd, but there is a
      trend that larger number of boys show aggression than girls.

PMID- 21965973
TI  - A control clinicial trial of a new anxiolytic 'clobazam'.
AB  - Clobazam as a twice-a-day dosage (10 mg-20 mg) regimen and Diazepam in a thrice-a
      day schedule (5 mg-5 mg-5 mg) were both effective in controlling moderate to
      severe anxiety neurosis. 83 patients were studied in a controlled, randomised,
      double-blind trial. Patients received active drug for the first six weeks and
      placebo for the next two weeks. Weekly evaluation was performed clinically for
      anxiolytic effect as well as effect on motor coordination studied on the Pursuit
      Rotor. Clobazam did not significantly differ from Diazepam in the dosage
      schedules studied. At the end of the two-week placebo treatment period, patients
      on Clobazam showed more improvement. Motor coordination was not impaired in both
      treatment groups. Clobazam treated patients had better motor performance at the
      end of the 14-day post-treatment placebo period. Side effects were reported with
      equal frequency in both the populations.

PMID- 21965974
TI  - Mental morbidity in industrial workers of khetri copper complex.
AB  - There is dearth of researches pertaining to prevalence of mental morbidity in
      Industrial setups, particularly in our country.They are important as
      psychological ill health of workers may adversely effect the productivity in
      developing country like India.Khetri Copper Complex in Rajasthan was selected for
      present study. Aims were to determine the period prevalence of mental morbidity
      among workers and role of sociodemographic, psychological variables in such
      disorders. 330 workers were randomly selected from various departments. Each
      worker was given specially designed proforma and Goldberg's General Health
      Questionnaire. Workers scoring 12 or more were given "A standardised psychiatric
      interview schedule" suspected cases were examined by senior consultants to assign
      them diagnostic categories (I.C.D.-9).Period Prevalence in this study was
      186.66/1000. As regards diagnostic categories, 75% were neurotic and 12.5%
      psychotics. Role of socio demographic, psychological and psychiatric variables in
      the development of these disorders has been discussed.Findings of this study are
      in expected direction and results obtained can be easily explained in terms of
      formulations given by other researchers in this field.Recommendation and plans
      for further research are discussed.

PMID- 21965975
TI  - Burden on families of schizophernic and chronic lung disease patients.
AB  - With the aims to find out the comparative burden on families of schizophrenics
      and patients with chronic lung disease and to study the areas of burden on
      families of two groups of patients, randomly selected samples of relatives of 25
      patients in each group were studied by using a structured interview schedule.
      Sociodemographic data were recorded and Burden on the family interview schedule
      was administered. Results revealed more burden on families of schizophrenic
      patients in the financial area, effects on family leisure, family routine, family
      interaction and mental health of other family members. Among the schizophrenic's
      families more financial burden was seen where male member had the illness. The
      implications of these findings in management and rehabilitation of the patients
      have been highlighted.

PMID- 21965976
TI  - Treatment of single impotent males.
AB  - A behaviourally oriented treatment programme for single males presenting with
      psychogenic impotence is described. The treatment consists of sexual-re
      education, guided imagery and masturbatory conditioning. The immediate results as
      well as the results of long-term follow up of those who completed the treatment
      are found to be encouraging.

PMID- 21965977
TI  - Stability of psychiatric diagnosis.
AB  - Eighty five charts of patients whose diagnoses have changed at least once between
      1977 and 1981 (unstable) were compared with another randomly chosen charts where
      diagnosis during the subsequent admissions remained unchanged (stable). Seventy
      six percent of the changes occurred from one to the other diagnostic category and
      remained so. Seventy three percent of Schizophrenics, 77.5% of Manics, 45% of
      Depressives and only 31% the Neurotics retained their original diagnosis. More
      Schizophrenics became Manics rather than the reverse. No statistically
      significant differences were found regarding changes between the other diagnostic
      categories. Unstable group had lesser frequency of admissions before the index
      admission and were more often readmitted.

PMID- 21965978
TI  - An exploratory study of the relation between psychoticism and certain aspects of
      auditory hallucinations in schizophrenics.
AB  - 30 schizophrenics who met the criteria of Feighner et al. and were having verbal
      auditory hallucination with or without hallucinations of other varieties were
      chosen for the study. Psychoticism was measured with the help of Eysenck's
      Personality Questionnaire. The relation of psychoticism scores to different
      aspects of auditory hallucinations was examined. High psychoticism scores seemed
      to be associated with a greater number of languages of the voice, known living
      'speakers' and less fear and passive listening during the voice.

PMID- 21965979
TI  - Prevention and control of drug abuse in the third world.

PMID- 21965980
TI  - Trihexyphenidyl dependence-report of two cases.
AB  - Two cases of normal dose dependence on Trihexyphenidyl are reported. The
      literature on anti parkinsonian drug abuse and dependence is briefly reviewed.

PMID- 21965982
TI  - The capitation fee and medical education.

PMID- 21965981
TI  - PSYCHO-DYNAMICS OF KORO: (A Case Report).

PMID- 21965983
TI  - Psychiatric morbidity in an urban slum-dwelling community.
AB  - The present study concerns the prevalence of psychiatric morbidity in a slum area
      in Calcutta and its relation to certain demographic and social variables. The
      survey was carried out by a team of psychiatrists by a door-to-door enquiry.
      Significant relationship of mental morbidity were found with age, sex, caste,
      socioeconomic status and family size.

PMID- 21965984
TI  - Lithium carbonate in the treatment of manic depressive psychosis in children.
AB  - The authors present their experience of prophylactic lithium therapy in seven
      children diagnosed as manic depressive psychosis, bipolar type, according to
      International Classification of Diseases, 9th revision. The authors demonstrate
      the effectiveness of lithium as a therapeutic and prophylactic agent for manic
      depressive illness in children. Side-effects are not a problem if serum lithium
      levels are maintained between 0.6-1.2 mEq/L. Renal functions have remained un
      impaired even after three years of lithium therapy in four children.

PMID- 21965985
TI  - Negative symptoms and negative schizophrenia.
AB  - This study determines the frequency distribution of prominent negative symptoms
      in a group of chronic, hospitalised schizophrenics. Thirty chronic Schizophrenic
      (D.S.M. III) patients were rated on the scale for Assessment of Negative Symptoms
      (SANS) and the prominent negative symptoms were correlated with age, sex and
      certain illness variables. Majority (80%) of patients had some or the other
      negative symptom, except thought blocking which was found in none. The subjective
      awareness of the symptoms was poor. Most negative symptoms were present to a
      severe degree in about 40% of cases. However, no significant correlation was
      found between severe negative symptoms and age or sex. Similarly, duration of
      illness, duration of hospitalisation or current medications did not influence
      negative symptoms to any appreciable degree. The implications are discussed.

PMID- 21965986
TI  - A study of interference with the activities of schizophrenics by auditory
      hallucinations.
AB  - Interference with self-care, occupation, social activities and leisure time
      activities by auditory hallucinations was examined in 30 schizophrenics. 9
      Patients did not experience interference with their activities. Psychoticism
      scores, neuroticism scores, presence of advising voices and presence of known
      living 'speakers' were related to interference with activities by the voices.

PMID- 21965987
TI  - Sexual behaviour in normal and neurotic females.
AB  - Relationship of neurosis and sexual-behaviour has been a controversial issue to
      date. This study was designed to explore (a) whether sexual dysfunctions are
      responsible for development of neurosis, (b) does neurosis affect sexual
      behaviour. In the present study sexual-behaviour of 53 married female neurotics
      and 32 matched healthy controls was studied. Health subjects were screened by
      Corncell Medical Index. A sexual-behaviour questionnaire was administered to all
      subjects. Experimental subjects were enquired about the sexual behaviour at two
      periods (a) before the onset of neurotic illness, (b) after the co-commencement
      of neurotic illness. These observations were compared with those of healthy
      subjects as well as between the two periods. Sexual-behaviour of neurotics was no
      way different to that of healthy control before the onset of illness. However,
      after the commencement of illness experimental subjects showed significant
      decreases in sexual satisfaction (sexual adequacy) in comparison to their pre
      illness sexual behavior as well as from that of healthy controls. These results
      tend to refute the first proposition of holding sexual disturbances responsible
      for development of neurotic-illnesses but support the notion of presence of
      sexual-disturbances during illness.

PMID- 21965988
TI  - Role of stressful life events in mania.
AB  - The study investigated the role of stressful life events and family pathology in
      manic illness-selecting 30 cases of mania from Psychiatric Centre Jaipur and 30
      normal controls from paramedical staff of psychiatric hospital. Both manics and
      normals were matched in terms of age, sex, education, marital status etc. All the
      subjects were subjected to Paykel's life events questionnaire, and an intensive
      psychiatric interview. Results revealed the significance of life stresses and
      family pathology in the genesis of mania. Death of close relative, financial
      difficulties, death of spouse, disappointment due to defeat in election, turned
      out to be major life events in contribution of manic pathology.

PMID- 21965989
TI  - Immunoglobulin patterns in schizophrenic patients.
AB  - Immunoglobulins G, M and A were estimated in serum and cerebrospinal fluid (CSF)
      of 30 schizophrenics, 20 neurological controls and 20 surgical controls.
      Significant increased levels of serum Ig A and M were detected in schizophrenics.
      An association was observed between increasing levels of serum IgA and IgM with
      the duration of disease and the number of episodes. CSF IgG/TP% was also
      significantly increased with the severity of the disease. On the basis of viral
      aetiology of schizophrenia it can be concluded that the increase in
      immunoglobulins synthesis might be due to the persistent antigenic stimulation.

PMID- 21965990
TI  - A study of coping with auditory hallucinations in schizophrenics.
AB  - The general orientation and activities involved in coping with auditory
      hallucinations were examined in 30 schizophrenics. Age, personality dimensions,
      duration of illness, position, loudness and pitch of the voice and interference
      with activities of patients by the voice were associated with the general
      orientation. Systematic coping behavior was useful. Socio-economic status and
      degree of interference with activities were associated with the choice of useful
      orientation. Manipulation of arousal and control of attention were beneficial.
      Neuroticism, interference due to voice, emotional intensity during the voice,
      'third person' voices and anticipation of voice were related to suicidal ideas.

PMID- 21965991
TI  - Serum lipids in anxiety neurosis.
AB  - Serum cholesterol, total triglycerides, HDL-cholesterol, LDL-cholesterol, VLDL
      cholesterol, free cholesterol and total phospholipids were studied in 36 patients
      of anxiety neurosis and 24 control subjects. Serum triglycerides, VLDL
      cholesterol and free-cholesterol were found to be significantly raised while
      esterified cholesterol WJS significantly lowered in anxiety neurosis. A
      significant negative correlation was observed between the anxiety score and free
      cholesterol in ferrule patients. The significance of these findings has been
      discussed.

PMID- 21965992
TI  - Case report : carbamazepine therapy in schizophrenia.
AB  - 9 cases of schizophrenia meeting Spitzer's Research Diagnostic Criteria and
      nonrespondent to conventional treatment were treated with carbamazepine, either
      alone or in combination with neuroleptics and 7 cases had shown improvement.

PMID- 21965993
TI  - Wilson'S disease presenting with schizophrenia like psychosis : a case report.

PMID- 21965994
TI  - Black-patch psychosis with sympathetic ophthalmitis and deafness.
AB  - A case of sympathetic ophthalmia with sensory-neural deafness, who developed a
      'black patch psychosis' following loss of vision and hearing, is described.
      Sympathetic ophthalmitis as a cause of this variety of delirium has not been
      described earlier.

PMID- 21965995
TI  - Isoniazid induced claustrophobia-a case report.
AB  - A case of claustrophobia in a 45-year old male tuberculous in-patient receiving
      antituberculous drug is reported. The patient presented with the clinical
      features of claustrophobia after eighteen months of therapy. Isoniazid was,
      probably, the most likely cause since. The symptoms recurred on reintroduction of
      INH containing regimens. There was no recurrence of symptoms on resumption of non
      Isoniazid regimen. Neurop3ychi.-Uric side-effects due to Isoniazid are well-known
      but Phobic neurosis due to Isoniazid was not reported till now.

PMID- 21965997
TI  - General hospital psychiatry and undergraduate medical education.

PMID- 21965996
TI  - National mental health plan and general hospital psychiatry.

PMID- 21965998
TI  - Liaison psychiatry in general hospitals.

PMID- 21965999
TI  - General hospital psychiatry and mental health legislation.

PMID- 21966000
TI  - General hospital in postgraduate psychiatric training and research.

PMID- 21966002
TI  - Cult of violence.

PMID- 21966001
TI  - General hospital psychiatry : role in clinical psychology.

PMID- 21966003
TI  - History of mental hospitals in Indian sub-continent.

PMID- 21966004
TI  - Depressive illness in India.

PMID- 21966005
TI  - Heroin dependence : the new delhi experience.
AB  - Socio-demographic and clinical profile of the first one hundred and five patients
      attending a de-addiction clinic of New Delhi for heroin dependence is presented.
      It reveals a sudden rise of Heroin use in young educated males, probably because
      of its easy availability and its decreasing prices in the last few years. This
      trend is likely to be observed in the other metropolitan cities of India as well.
      Need for strengthening of preventive, curative and rehabilitative services is
      emphasized.

PMID- 21966006
TI  - Changing patterns of admission in a state mental hospital.
AB  - The patterns of admission in a State Mental Hospital during the past decade (1st
      January 1973 to 31st December 1932) was studied. It was observed that voluntary
      admissions gradually increased whereas certified admissions declined over the
      decade. The certified cases from Madras City showed a decline in the recent years
      after some fluctuations and the certified cases from Districts of Tamil Nadu
      remained almost constant throughout the decade. The admissions from Madras City
      increased whereas the admissions from the Districts of Tamil Nadu showed a
      tendency to decline. The reasons for the above observations are discussed.

PMID- 21966007
TI  - Chronic schizophrenia-a psychopharmacological aproach.
AB  - Our work suggests that the Leonhard classification system holds much pron.ise as
      a framework for future neurological development. One might speculate along
      biochemical lines that the nonsystematic subpopulation of schizophrenics may
      suffer from altered dopamine beta-hydroxylase activity which results in an excess
      of dopamine, This would eeplain why this class responds so well to dopamine
      receptor blocking agent when other patient do not.One might also speculate tint
      we are dealing with a number of diseases-each with different courses and
      progressing to different end states, but all with common pattern during the acute
      stage, e.g., increased dopamine levels or receptor sensitivity levels. This is
      probably why the acute stage can usually be controlled by the administration of a
      dopamine receptor blocking agent.A further speculation concerns the catatonic
      patient- who had begun to respond to psychosocial and milieu treatment prior to
      the introduction of neuroleptics. This particular group of patients do not seem
      to benefit from prophylactic treatment with neuroleptics. If, by activating a
      patient, catecholamines are released, it is hypothesized that the Catatonics are
      a completely separate subpopulation-not just clinically-but also
      biochemically.Completely different types of drugs may be helpful for the
      different schizophrenic subpopulations. Among the various substances, propranolol
      should be considered. Obviously, this drug will not be effective in all
      schizophrenics; but there arc certain types of patients who respond to beta
      blockers. There is also increasing evidence that clordine (which stimulates alpha
      adrenergic receptors) may also have an effect on certain schizophrenics The most
      recent findings is that cholecystokinin-thought for Some time to be an
      exclusively peripheral substance-appears to be present in the brain and available
      in the form of ceulotide, a neuropeptide which is a dopamine agonist. This
      susbtance, also, seems to be effective in the treatment of certain
      schizophrenics.Chronic schizophrenia requires re-evaluation and it should be
      recognized that different drugs are effective in different types of patients.
      There is renewed interest in the various schizophrenic conditions and their end
      states. We must hope that the pharmacologists, provided with sufficient
      information, will search for new drugs with differentiated activities that will
      meaningfully influence the end states of schizophrenic disorders and/or prevent
      their development.

PMID- 21966008
TI  - Standardisation of the cattell's infant intelligence scale in India.
AB  - 301 children were tested longitudinally upto 3 years using the Cattell's Infant
      Intelligence Scale. The data was subjected to item analysis and validity and
      reliability calculated. It was found that with a few modifications Cattell's
      scale could be profitably used in relevant areas in psychiatric practice for the
      assessment of children below 3 years of mental age.

PMID- 21966009
TI  - Mode of spread of epidemic koro in a village in west bengal.
AB  - The mode of spread of epidemic Koro in a village in West Bengal has been
      described and the psychological principles involved in it have been explained.

PMID- 21966010
TI  - Family structure, dynamics and psychiatric disorder in India.
AB  - This paper briefly reviews the literature on family structure, dynamics and
      relationships between family-jointness and different psychiatric disorders in
      India. Many recent studies indicate that the nuclear families are more vulnerable
      and plea is made for maintaining the traditional joint family system, even in
      some modified forms, because of its "built-in-immunity" and supportive networks.

PMID- 21966011
TI  - A double blind comparative study of usefulness of diphenoxylate and propoxyphene
      napsylate in the withdrawal treatment of opium addicts.

PMID- 21966012
TI  - Screening of organic brian dysfunction.
AB  - One hundred eighty adult patients (age 20 to 50 years) referred to Psychology
      section for differential diagnosis of brain pathology from 1976 to 1980 and where
      at least two of the three cognitive functions- intelligence, memory, and percepto
      motor ability, were tested and clinical diagnosis arrived at follow-ups, etc.
      were included. Nineteen psychological test variables were rescored to minimize
      the effect of age and education. Frequency distributions, separately for brain
      damage and non-brain damage patients for each variable were obtained and ogives
      prepared to find out points of maximum differentiations. Scores were assigned
      ratings of 0, 2 & 3 for average to low scores, and combined rating could identify
      about 2/3rd of organics correctly amongst the difficult to diagnose cases.

PMID- 21966013
TI  - Family jointness, social interaction and neuroses : a rural urban comparison.
AB  - The association between family patterns and neurotic illness has been reported
      variously in India. Previous work from our centre seems to suggest that a joint
      family provides better support and security to vulnerable individuals. The
      present work is a community based project conducted in a selected rural and an
      urban area. The door to door survey by the research team identified index
      subjects who were screened for presence of psychotic illness before being
      included. Non psychotic psychiatric disorders were identified using the Cornell
      Medical Index and Khatri's scale was used for typing the family pattern. The
      social interaction schedule was the major instrument to quantify the type and
      duration of interaction, and life events were scaled using the modified Life
      Events inventory.Our results indicate that whereas the joint family system was
      prevalent in the rural areas, the major family constellation in the urban areas
      was nuclear. Though the primary group of the rural respondent was richer, the
      average member of the urban area spent more time in interaction and thus utilized
      the support system better. The results are discussed for their relevance to the
      understanding of the genesis of neurotic disorders.

PMID- 21966014
TI  - Treatment of writer's cramp : a follow up study.
AB  - The paper describes the usefulness of a treatment method for writer's cramp.
      Three cases of writer's cramp are described and in all the three, the response to
      treatment has been good after treatment and on follow up.

PMID- 21966015
TI  - A follow-up study of mental retardation focussing on parental attitudes.
AB  - The investigation studies the perception and attitudes of patents towards their
      mentally retarded child. Thirty such children were followed up after one year of
      initial contact and the parents were interviewed. Parents of higher education had
      a more scientific perception. Most parents had unrealistic hopes and
      expectations, feelings of shame, guilt and self blame were predominant.
      Rejection, hostility neglect of child and other negative attitudes were
      significantly more often seen in younger parents, urbanites and those with higher
      education. The negative attitudes were more towards a child with additional
      psychiatric problems. This information could be of great advmuge in managing
      families with a retarded child.

PMID- 21966016
TI  - Lithium in affective disorders : a seven year observation of lithium clinic.
AB  - Out of 692 patients registered in the lithium clinic, King George's Medical
      College, Lucknow, 122 patients suffering from affective disorders, receiving
      lithium for at least 6 months continuously, having had at least 5 serum lithium
      estimations done and having been evaluated at least once in 6 months while on
      follow-up, were analysed with a view to study the relapses. About one-third
      patients suffered no relapse while on lithium. The study revealed that longer the
      duration of lithium treatment lesser were the frequency, number, intensity and
      duration of manic/depressive relapses. Majority of patients were maintained on
      the lower side (0.5-0.8 mEq/L) of the usually recommended therapeutic range (0.6
      1.2 mEq/L) for lithium prophylaxis. Commonly observed side effects include fine
      tremors, muscular weakness, polyuria, polydipsia and constipation. All the side
      effects were easily managed and none had a fatal sides-effect. A reappraisal in
      the light of existing literature of lithium prophylaxis on manic depressive
      psychosis is done.

PMID- 21966017
TI  - Personality characteristics of alcoholics dropping out of treatment.
AB  - Twenty seven male alcoholics were prospectively studied to find out the
      characteristics of those who drop out soon after discharge from the hospital.
      Seven persons, failed to make a single visit over a six-month period, and were
      termed 'dropouts'.On admission, after detoxification, all 27 patients were
      individually administered, the following tests:(1) Bhatia's Performance Test of
      Intelligence(2) Multiphasic Questionnaire(3) Internal-External Locus of Control
      Scale and(4) 16 P. F. Questionnaire (Form C).Dropouts did not differ from the
      completers on any of the socio-demographic or clinical variables. Two personality
      characteristics significantly differentiated the dropouts from the completers.

PMID- 21966019
TI  - A model for prevention and treatment of depression in developing nations.

PMID- 21966018
TI  - Sexual behaviour in schizophrenic patients on neuroleptic medication.
AB  - Sexual behaviour in forty mile schizophrenics on maintenance medication were
      studied. Authors observed that thirteen patients reported decrease in frequency
      of sexual thoughts, fifteen in frequency of intercourse. Eight patients reported
      decline in enjoyment of intercourse and six avoided sex.

PMID- 21966020
TI  - A case of unusual sexual perversion.

PMID- 21966021
TI  - Cotard'S syndrome in schizophrenia : a case report.

PMID- 21966022
TI  - Psychological aspects of hypothyroidism (review and case study).
AB  - The psychological aspects of hypothyroidism are reviewed with reference to the
      available literature. A case history of hypothyroidism along with its
      psychological manifestations is discussed and a conclusion is drawn that usually
      four characteristic types of psychological pictures co-exist with hypothyroidism
      viz. organic brain syndrome, schizophrenia form psychoses, affective psychosis,
      especially the depression and mixed variety. Suggestion for therapy are also
      outlined.

PMID- 21966023
TI  - Synthesis, structure and pi-delocalization of a phosphaalkenyl based neutral PNP
      pincer.
AB  - Preparation, characterization and structural properties of a novel bis
      phosphaalkenyl based PNP-pincer are reported. In this pincer the pi-system is
      delocalized over all three donor sites, which was demonstrated with DFT
      calculations, UV-Vis measurements and structural findings. As a consequence of
      this extended delocalization the pi-system reveals near coplanarity which is
      evident from the first crystal structure for an uncomplexed bisphosphaalkenyl PNP
      pincer.

PMID- 21966024
TI  - Doing the Scut Work of Infant Care: Does Religiousness Encourage Father
      Involvement?
AB  - Considerable debate exists regarding whether religiousness promotes or impedes
      greater father involvement in parenting. Our study addresses this issue using a
      Midwestern longitudinal dataset that tracks the transition to first parenthood
      for 169 married couples. We focus on performance of the "messier" tasks of infant
      care. We find little evidence that religiousness enhances father involvement in
      this domain. Biblically conservative couples exhibit a greater gender gap in
      childcare than others, with mothers more involved than fathers. The gender gap is
      also greater the more fathers work outside the home, the greater mothers'
      knowledge of infant development, and the more unadaptable the infant. Average
      daily childcare is lower the greater spouses' work hours, but higher with
      difficult pregnancies or fussy babies.

PMID- 21966025
TI  - MR molecular imaging of angiogenesis using targeted perfluorocarbon
      nanoparticles.

PMID- 21966026
TI  - A compact model for early electromigration failures of copper dual-damascene
      interconnects.
AB  - A compact model for early electromigration failures in copper dual-damascene
      interconnects is proposed. The model is based on the combination of a complete
      void nucleation model together with a simple mechanism of slit void growth under
      the via. It is demonstrated that the early electromigration lifetime is well
      described by a simple analytical expression, from where a statistical
      distribution can be conveniently obtained. Furthermore, it is shown that the
      simulation results provide a reasonable estimation for the lifetimes.

PMID- 21966027
TI  - SPR imaging biosensor for the 20S proteasome: sensor development and application
      to measurement of proteasomes in human blood plasma.
AB  - The 20S proteasome is a multicatalytic enzyme complex responsible for
      intracellular protein degradation in mammalian cells. Its antigen level or
      enzymatic activity in blood plasma are potentially useful markers for various
      malignant and nonmalignant diseases. We have developed a method for highly
      selective determination of the 20S proteasome using a Surface Plasmon Resonance
      Imaging (SPRI) technique. It is based on the highly selective interaction between
      the proteasome's catalytic beta5 subunit and immobilized inhibitors (the
      synthetic peptide PSI and epoxomicin). Inhibitor concentration and pH were
      optimized. Analytical responses, linear ranges, accuracy, precision and
      interferences were investigated. Biosensors based on either PSI and epoxomicin
      were found to be suitable for quantitative determination of the proteasome, with
      a precision of +/-10% for each, and recoveries of 102% and 113%, respectively,
      and with little interference by albumin, trypsin, chymotrypsin, cathepsin B and
      papain. The proteasome also was determined in plasma of healthy subjects and of
      patients suffering from acute leukemia. Both biosensors gave comparable results
      (2860 ng.mL-1 on average for control, and 42300 ng.mL-1 on average for leukemia
      patients).FigureThe synthetic peptide aldehyde Z-Ile-Glu(OBut)-Ala-Leu-H (PSI)
      and a microbial alpha',beta' epoxyketone peptide epoxomicin was used to develop
      SPRI biosensor for the highly selective determination of the 20S proteasome
      concentration, and to evaluate the sensor applicability for the determination of
      20S proteasome in human blood plasma.

PMID- 21966028
TI  - Thermo-Mechanical Properties of Semi-Degradable Poly(beta-amino ester)-co-Methyl
      Methacrylate Networks under Simulated Physiological Conditions.
AB  - Poly(beta-amino ester) networks are being explored for biomedical applications,
      but they may lack the mechanical properties necessary for long term implantation.
      The objective of this study is to evaluate the effect of adding methyl
      methacrylate on networks' mechanical properties under simulated physiological
      conditions. The networks were synthesized in two parts: (1) a biodegradable
      crosslinker was formed from a diacrylate and amine, (2) and then varying
      concentrations of methyl methacrylate were added prior to photopolymerizing the
      network. Degradation rate, mechanical properties, and glass transition
      temperature were studied as a function of methyl methacrylate composition. The
      crosslinking density played a limited role on mechanical properties for these
      networks, but increasing methyl methacrylate concentration improved the toughness
      by several orders of magnitude. Under simulated physiological conditions,
      networks showed increasing toughness or sustained toughness as degradation
      occurred. This work establishes a method of creating degradable networks with
      tailorable toughness while undergoing partial degradation.

PMID- 21966029
TI  - Conditional Discriminations by Preverbal Children in an Identity Matching-to
      Sample Task.
AB  - This study sought to develop methodology for assessing whether children aged 16
      21 months could learn to match stimuli on the basis of physical identity in
      conditional discrimination procedures of the type routinely used in stimulus
      equivalence research with older participants. The study was conducted in a
      private room at a daycare center for children and toddlers. The child and the
      research sat together on the floor facing an apparatus with two windows. Stimuli
      to be discriminated were toys especially designed to attract the child's
      attention and maintain continued interest. On simple discrimination and
      discrimination reversal trials that were programmed in initial training, S+ and S
      toys were displayed within the two windows. When the child touched the window
      containing the toy defined as S+ on a given trial, s/he was allowed to
      manipulate/play with that toy. Selections of the S- toy ended the trial without a
      play opportunity. On subsequent identity matching-to-sample trials, the child was
      first allowed to manipulate a sample toy. Then, S+ (matching) and S-
      (nonmatching) comparison toys were displayed within the windows, and the
      selection consequences were the same as on simple discrimination trials. The
      study provides evidence that preverbal children can master simple and conditional
      discrimination performances via such procedures, perhaps setting the stage for
      subsequent studies aimed at establishing procedural control of the discrimination
      baselines needed to assess the stimulus equivalence potential of children in this
      age range.

PMID- 21966030
TI  - A Partially Linear Regression Model for Data from an Outcome-Dependent Sampling
      Design.
AB  - The outcome dependent sampling scheme has been gaining attention in both the
      statistical literature and applied fields. Epidemiological and environmental
      researchers have been using it to select the observations for more powerful and
      cost-effective studies. Motivated by a study of the effect of in utero exposure
      to polychlorinated biphenyls on children's IQ at age 7, in which the effect of an
      important confounding variable is nonlinear, we consider a semi-parametric
      regression model for data from an outcome-dependent sampling scheme where the
      relationship between the response and covariates is only partially parameterized.
      We propose a penalized spline maximum likelihood estimation (PSMLE) for inference
      on both the parametric and the nonparametric components and develop their
      asymptotic properties. Through simulation studies and an analysis of the IQ
      study, we compare the proposed estimator with several competing estimators.
      Practical considerations of implementing those estimators are discussed.

PMID- 21966032
TI  - Synthesis of a Diverse Library of N,N-Dimethylamino Containing Monomers
      Appropriate as Lipid Head Groups.
AB  - We report on the synthesis of a diverse library of N,N-dimethylamino containing
      monomers. Subjecting these monomers to Chabrier reaction conditions would yield
      lipids with polymerizable head groups. This library of lipid head groups is
      equipped with a variety of arm lengths containing reduction-oxidation
      polymerizable groups at the terminus.

PMID- 21966031
TI  - Synthesis and photophysics of an octathioglycosylated zinc(II) phthalocyanine.
AB  - A water soluble zinc(II) phthalocyanine symmetrically appended with eight
      thioglucose units was synthesized from commercially available
      hexadecafluorophthalocyaninatozinc(II) by controlled nucleophilic substitution of
      the peripheral fluoro groups. The photophysical properties and cancer cell uptake
      studies of this nonhydrolyzable thioglycosylated phthalocyanine are reported. The
      new compound has amphiphilic character, is chemically stable, and can potentially
      be used as a photosensitizer in photodynamic therapy.

PMID- 21966033
TI  - Suzuki-Miyaura Cross-Coupling of Benzylic Bromides Under Microwave Conditions.
AB  - A procedure for benzylic Suzuki-Miyaura cross-coupling under microwave conditions
      has been developed. These conditions allowed for heterocyclic compounds to be
      coupled. Optimum conditions found were Pd(OAc)(2), JohnPhos as the catalyst and
      ligand, potassium carbonate as base, and DMF as the solvent. Using these
      conditions, a library of structurally diverse compounds was synthesized.

PMID- 21966034
TI  - How to write your first research paper.
AB  - Writing a research manuscript is an intimidating process for many novice writers
      in the sciences. One of the stumbling blocks is the beginning of the process and
      creating the first draft. This paper presents guidelines on how to initiate the
      writing process and draft each section of a research manuscript. The paper
      discusses seven rules that allow the writer to prepare a well-structured and
      comprehensive manuscript for a publication submission. In addition, the author
      lists different strategies for successful revision. Each of those strategies
      represents a step in the revision process and should help the writer improve the
      quality of the manuscript. The paper could be considered a brief manual for
      publication.

PMID- 21966035
TI  - Reflections on searching for a postdoctoral position: three points to ponder.
AB  - Choosing the right laboratory in which to do postdoctoral training is perhaps one
      of the most important decisions that a scientist makes in his or her career. Does
      one choose a laboratory based on the research topic or the research style of the
      mentor? Does one choose a large laboratory or a small one? How does one fit the
      selection of a postdoctoral laboratory into the context of one's long-range
      career goals? Here, I briefly discuss three points worth considering in seeking a
      research laboratory for postdoctoral training after the completion of a graduate
      degree.

PMID- 21966036
TI  - The residency application abyss: insights and advice.
AB  - Most medical students apply for residency training upon completion of medical
      school. The choice of specialty is one of a student's first major career
      decisions, and the application process often results in considerable anxiety, as
      it is competitive, unpredictable, and requires a significant investment of time
      and money. This article, which addresses several important facets of the
      residency application using both experiential and evidence-based data, is
      organized chronologically into sections that describe a logical approach to
      applying for residency: choice of a specialty, the personal statement, the
      interview day, and developing a rank list. A list of relevant websites is also
      included. This paper is a resource that provides timely and tangible guidance to
      medical students applying for residency training.

PMID- 21966037
TI  - Medical students as medical educators: opportunities for skill development in the
      absence of formal training programs.
AB  - All physicians, at some point in their career, are responsible for the education
      of their peers and junior colleagues. Although medical students are expected to
      develop clinical and research skills in preparation for residency, it is becoming
      clear that a student should also be expected to develop abilities as a teacher. A
      handful of institutions have student-as-teacher programs to train medical
      students in education, but most students graduate from medical school without
      formal training in this area. When such a program does not exist, medical
      students can gain experience in education through participation in peer teaching,
      course design, educational committees, and medical education scholarship. In
      doing so, they attain important skills in the development, implementation, and
      evaluation of educational programs. These skills will serve them in their
      capacity as medical educators as they advance in their careers and gain
      increasing teaching responsibility as residents, fellows, and attending
      physicians.

PMID- 21966038
TI  - The bench vs. the blackboard: learning to teach during graduate school.
AB  - Many science, technology, engineering, and mathematics (STEM) graduate students
      travel through the academic career pipeline without ever learning how to teach
      effectively, an oversight that negatively affects the quality of undergraduate
      science education and cheats trainees of valuable professional development. This
      article argues that all STEM graduate students and postdoctoral fellows should
      undergo training in teaching to strengthen their resumes, polish their oral
      presentation skills, and improve STEM teaching at the undergraduate level. Though
      this may seem like a large undertaking, the author outlines a three-step process
      that allows busy scientists to fit pedagogical training into their research
      schedules in order to make a significant investment both in their academic career
      and in the continuing improvement of science education.

PMID- 21966039
TI  - Balancing science and family: tidbits of wisdom from those who've tried it and
      succeeded.
AB  - There is a notion that combining parenthood with a career in academic science is
      problematic, yet academic science careers can provide an outstanding career
      choice for professional parents because they offer extraordinary flexibility and
      stability. Much has been written about the paucity of women in tenure track
      scientific positions and the general disparity between men and women in all
      professions. However, the status quo is changing as more women fill the ranks of
      academia and male professors share childcare and household duties with spouses
      who hold professional positions. Although combining any career with parenthood
      can be challenging, parenthood should not be considered an obstacle to a
      successful scientific career.

PMID- 21966040
TI  - So you think you want to save the world.
AB  - There is increasing interest among both medical and other professional
      communities in becoming involved in global health, development, and other
      charitable work. There has also been a proliferation of opportunities in the
      field. Nonetheless, it is still difficult to find practical information on the
      daily realities of development work or advice on the difficulties inherent to
      this type of work. This article is intended for individuals who are interested in
      becoming involved in global health and development work. Through a discussion
      that touches on development economics, the history, psychology, and current state
      of development aid, the common conflicts, as well as the rewards of development
      work, this article aims to prepare the interested individual for the experience
      of global health and development work. The article also provides practical
      suggestions and references for those searching for an opportunity in the field,
      with an emphasis on global health opportunities.

PMID- 21966041
TI  - Plans of mice and men: from bench science to science policy.
AB  - The transition from bench science to science policy is not always a smooth one,
      and my journey stretched as far as the unemployment line to the hallowed halls of
      the U.S. Capitol. While earning my doctorate in microbiology, I found myself more
      interested in my political activities than my experiments. Thus, my science
      policy career aspirations were born from merging my love of science with my
      interest in policy and politics. After receiving my doctorate, I accepted the
      Henry Luce Scholarship, which allowed me to live in South Korea for 1 year and
      delve into the field of science policy research. This introduction into science
      policy occurred at the South Korean think tank called the Science and Technology
      Policy Institute (STEPI). During that year, I used textbooks, colleagues, and
      hands-on research projects as my educational introduction into the social science
      of science and technology decision-making. However, upon returning to the United
      States during one of the worst job markets in nearly 80 years, securing a
      position in science policy proved to be very difficult, and I was unemployed for
      five months. Ultimately, it took more than a year from the end of the Luce
      Scholarship to obtain my next science policy position with the American Society
      for Microbiology Congressional Fellowship. This fellowship gave me the
      opportunity to work as the science and public health advisor to U.S. Senator
      Harry Reid. While there were significant challenges during my transition from the
      laboratory to science policy, those challenges made me tougher, more
      appreciative, and more prepared to move from working at the bench to working in
      the field of science policy.

PMID- 21966042
TI  - Choosing a career: online resources for every scientist.
AB  - Looking for a job? Not even sure what kind of job you are looking for? Don't wait
      until all your experiments are wrapped up and your manuscript is in press. While
      slaving away doing research, it is easy to lose sight of what comes next. But
      graduate students and postdoctoral researchers should start planning the next
      chapter of their careers before the end is in sight. This article highlights
      different online resources for choosing a career and finding a job.

PMID- 21966043
TI  - Changing the science education paradigm: from teaching facts to engaging the
      intellect: Science Education Colloquia Series, Spring 2011.
AB  - Dr. Jo Handelsman, Howard Hughes Medical Institute Professor in the Department of
      Molecular, Cellular and Developmental Biology at Yale University, is a long-time
      devotee of scientific teaching, receiving this year's Presidential Award for
      Science Mentoring. She gave a seminar entitled "What is Scientific Teaching? The
      Changing Landscape of Science Education" as a part of the Scientific Education
      Colloquia Series in spring 2011. After dissecting what is wrong with the status
      quo of American scientific education, several ideological and practical changes
      are proposed, including active learning, regular assessment, diversity, and
      mentorship.

PMID- 21966044
TI  - Research on and in medical education.
AB  - Dr. George Lister of the University of Texas Southwestern Medical Center
      delivered the Lee E. Farr Lecture on Student Research Day on May 9, 2011. This
      day focused on the dissertation work of Yale School of Medicine MD students,
      whose research opportunities for prospective physicians were recently examined
      and critiqued by Yale's Committee to Promote Student Interest in Careers as
      Physician Scientists. Lister's talk served to highlight the importance of
      communication between the laboratory and the clinic in optimizing diagnostics and
      treatments, effectively affirming the validity of the Committee's objectives.

PMID- 21966045
TI  - Sowing the seeds for a career in medicine: reflections and projections.
AB  - Dr. George Lister delivered the following presentation as the Lee E. Farr
      Lecturer on May 8, 2011, which served as the culmination of the annual Student
      Research Day at Yale School of Medicine. He is the Chair of Pediatrics at the
      University of Texas Southwestern Medical School and Pediatrician-in-Chief at
      Children's Medical Center of Dallas. In his lecture to the medical students, who
      had just completed their research theses, Dr. Lister discusses his own work on
      sudden infant death syndrome (SIDS), demonstrating the complexity of clinical
      research and proving insight into the traits required of physician scientists.
      Committed to medical education and recognized by several awards for his
      mentorship, he ends the talk by imparting valuable advice on future physicians.

PMID- 21966046
TI  - The Flexner Report--100 years later.
AB  - The Flexner Report of 1910 transformed the nature and process of medical
      education in America with a resulting elimination of proprietary schools and the
      establishment of the biomedical model as the gold standard of medical training.
      This transformation occurred in the aftermath of the report, which embraced
      scientific knowledge and its advancement as the defining ethos of a modern
      physician. Such an orientation had its origins in the enchantment with German
      medical education that was spurred by the exposure of American educators and
      physicians at the turn of the century to the university medical schools of
      Europe. American medicine profited immeasurably from the scientific advances that
      this system allowed, but the hyper-rational system of German science created an
      imbalance in the art and science of medicine. A catching-up is under way to
      realign the professional commitment of the physician with a revision of medical
      education to achieve that purpose.

PMID- 21966047
TI  - Development of a pH-responsive particulate drug delivery vehicle for localized
      biologic therapy in inflammatory bowel disease.
AB  - The treatment of inflammatory bowel disease (IBD) recently has been
      revolutionized by the introduction of protein-based biologic therapies. However,
      biologic therapy is complicated by the requirement for administration with a
      needle, systemic side effects, and high cost. Particulate drug delivery systems
      have been shown to deliver drugs locally to the intestinal mucosa via oral
      administration. However, these systems have been largely unexplored for the
      delivery of biologics due to harsh particle fabrication conditions and the
      tendency of many particulate formulations to dissolve in the acidic upper GI
      tract. We have, therefore, fabricated an inexpensive and non-toxic novel
      microparticle capable of encapsulating proteins. We establish that the particle
      retains its contents at acidic pH and releases them at neutral pH. We also
      demonstrate particulate encapsulation of interleukin-10 (IL-10), a protein
      relevant to the treatment of IBD, at an encapsulation efficiency of 14.3 percent.
      Such a vehicle is promising for its oral route of administration and potential to
      decrease side effects and increase potency of biologics.

PMID- 21966048
TI  - Achilles tendon rupture: avoiding tendon lengthening during surgical repair and
      rehabilitation.
AB  - Achilles tendon rupture is a serious injury for which the best treatment is still
      controversial. Its primary goal should be to restore normal length and tension,
      thus obtaining an optimal function. Tendon elongation correlates significantly
      with clinical outcome; lengthening is an important cause of morbidity and may
      produce permanent functional impairment. In this article, we review all factors
      that may influence the repair, including the type of surgical technique, suture
      material, and rehabilitation program, among many others.

PMID- 21966049
TI  - RNA-based gene therapy for the treatment and prevention of HIV: from bench to
      bedside.
AB  - Gene therapy is considered a feasible approach for the treatment and prevention
      of HIV/AIDS. Targeting both viral genes and host dependency factors can interfere
      with the viral lifecycle and prevent viral replication. A number of approaches
      have been taken to target these genes, including ribozymes, aptamers, and RNAi
      based therapies. A number of these therapies are now beginning to make their way
      into clinical trials and providing proof of principle that gene therapy is a safe
      and realistic option for treating HIV. Here, we focus on those therapies that
      have progressed along the pipeline to preclinical and clinical testing.

PMID- 21966050
TI  - Therapeutic advances in the management of Huntington's disease.
AB  - Trinucleotide repeat disorders are a set of genetic disorders characterized by
      the expansion of certain genes of a segment of DNA that contains a repeat of
      three nucleotides, thus exceeding the normal stable threshold. These repeats in
      the DNA cause repeats of a specific amino acid in the protein sequence, and it is
      the repeated amino acid that results in a defective protein. Huntington's disease
      is a well-known genetic disorder associated with trinucleotide repeat expansions.
      Patients first present clinically in midlife and manifest a typical phenotype of
      sporadic, rapid, and involuntary control of limb movement; stiffness of limbs;
      impaired cognition; severe psychiatric disturbances; and ultimately, death. There
      have been a number of therapeutic advances in the treatment of Huntington's
      disease, such as foetal neural transplantation, RNA interference, and
      transglutaminase inhibitor. Although there is intensive research into
      Huntington's disease and recent findings seem promising, effective therapeutic
      strategies may not be developed until the next few decades.

PMID- 21966052
TI  - Multivariate Failure Times Regression with a Continuous Auxiliary Covariate.
AB  - How to take advantage of the available auxiliary covariate information when the
      primary covariate of interest is not measured is a frequently encountered
      question in biomedical study. In this paper, we consider the multivariate failure
      times regression analysis in which the primary covariate is assessed only in a
      validation set but a continuous auxiliary covariate for it is available for all
      subjects in the study cohort. Under the frame of marginal hazard model, we
      propose to estimate the induced relative risk function in the nonvalidation set
      through kernel smoothing method and then obtain an estimated pseudo-partial
      likelihood function. The proposed estimated pseudo-partial likelihood estimator
      is shown to be consistent and asymptotically normal. We also give an estimator of
      the marginal cumulative baseline hazard function. Simulations are conducted to
      evaluate the finite sample performance of our proposed estimator. The proposed
      method is illustrated by analyzing a heart disease data from Studies of Left
      Ventricular Dysfunction (SOLVD).

PMID- 21966051
TI  - Relapse of polymicrobial endocarditis in an intravenous drug user.
AB  - A 26-year-old male intravenous drug user (IDU) presented twice within 6 months
      with relapsed polymicrobial infective endocarditis (IE) due to Eikenella
      corrodens and Streptococcus constellatus after completing two courses of
      appropriate antimicrobial therapy. This report points to relapsing endocarditis
      as a clinical entity that warrants attention in IDUs when E. corrodens or S.
      constellatus are causative agents of IE.

PMID- 21966053
TI  - Actions of Tefluthrin on Rat Na(v)1.7 Voltage-Gated Sodium Channels Expressed in
      Xenopus Oocytes.
AB  - In rats expression of the Na(v)1.7 voltage-gated sodium channel isoform is
      restricted to the peripheral nervous system and is abundant in the sensory
      neurons of the dorsal root ganglion. We expressed the rat Na(v)1.7 sodium channel
      alpha subunit together with the rat auxiliary beta1 and beta2 subunits in Xenopus
      laevis oocytes and assessed the effects of the pyrethroid insecticide tefluthrin
      on the expressed currents using the two-electrode voltage clamp method.
      Tefluthrin at 100 uM modified of Na(v)1.7 channels to prolong inactivation of the
      peak current during a depolarizing pulse, resulting in a marked "late current" at
      the end of a 40-ms depolarization, and induced a sodium tail current following
      repolarization. Tefluthrin modification was enhanced up to two-fold by the
      application of a train of up to 100 5-ms depolarizing prepulses. These effects of
      tefluthrin on Na(v)1.7 channels were qualitatively similar to its effects on rat
      Na(v)1.2, Na(v)1.3 and Na(v)1.6 channels assayed previously under identical
      conditions. However, Na(v)1.7 sodium channels were distinguished by their low
      sensitivity to modification by tefluthrin, especially compared to Na(v)1.3 and
      Na(v)1.6 channels. It is likely that Na(v)1.7 channels contribute significantly
      to the tetrodotoxin-sensitive, pyrethroid-resistant current found in cultured
      dorsal root ganglion neurons. We aligned the complete amino acid sequences of
      four pyrethroid-sensitive isoforms (house fly Vssc1; rat Na(v)1.3, Na(v)1.6 and
      Na(v)1.8) and two pyrethroid-resistant isoforms (rat Na(v)1.2 and Na(v)1.7) and
      found only a single site, located in transmembrane segment 6 of homology domain
      I, at which the amino acid sequence was conserved among all four sensitive
      isoform sequences but differed in the two resistant isoform sequences. This
      position, corresponding to Val410 of the house fly Vssc1 sequence, also aligns
      with sites of multiple amino acid substitutions identified in the sodium channel
      sequences of pyrethroid-resistant insect populations. These results implicate
      this single amino acid polymorphism in transmembrane segment 6 of sodium channel
      homology domain I as a determinant of the differential pyrethroid sensitivity of
      rat sodium channel isoforms.

PMID- 21966054
TI  - Influence of Imidazolium Ionic Liquids on Dehydrogenase Activity of Activated
      Sludge Microorganisms.
AB  - Imidazolium salts are one of the most often used and investigated groups of ionic
      liquids (ILs). The research concerning their ecotoxicity comprised many test
      organisms representing different trophic levels; however, their impact on mixed
      cultures of microorganisms such as activated sludge has been hardly ever
      investigated. Thus, in this work, the effect of imidazolium ionic liquids on
      dehydrogenase activity of activated sludge was estimated. Three activated sludges
      of different properties and origin were tested. It occurred that 1-alkyl-3-methyl
      imidazolium bromides do not inhibit dehydrogenase activity of sludge, if the
      alkyl chain contains up to six carbon atoms. The values of IC50 for these ILs
      were above 100 mg l(-1). At the same time, the inhibitory effect on dehydrogenase
      activity of activated sludge increases with the increase in chain length of the
      alkyl substituent. The degree of inhibition of dehydrogenase activity of sludge
      microorganisms is dependent on activated sludge properties.

PMID- 21966055
TI  - PROBLEM PROFILES OF AT-RISK YOUTH IN TWO SERVICE PROGRAMS: A MULTI-GROUP,
      EXPLORATORY LATENT CLASS ANALYSIS.
AB  - Baseline data collected in two brief intervention projects (BI-Court and Truancy
      Project) were used to assess similarities and differences in subgroups of at-risk
      youth. Classifications of these subgroups were based on their psychosocial
      characteristics (e.g., substance use). Multi-group latent class analysis (LCA)
      identified two BI-Court subgroups of youth, and three Truant subgroups. These
      classes can be viewed as differing along two dimensions, substance use
      involvement and emotional/behavioral issues. Equality tests of means across the
      latent classes for BI-Court and Truancy Project youths found significant
      differences that were consistent with their problem group classification. These
      findings highlight the importance of quality assessments and allocating
      appropriate services based on problem profiles of at-risk youth.

PMID- 21966056
TI  - Scoring sleep in neurological patients: the need for specific considerations.

PMID- 21966057
TI  - The challenges of interpreting residual effects of hypnotics.

PMID- 21966058
TI  - Sleep EEG, the clearest window through which to view adolescent brain
      development.

PMID- 21966059
TI  - Why can't my child sleep and will there be long-term consequences? Lessons from
      prospective community-based studies.

PMID- 21966060
TI  - The association between short sleep duration and weight gain is dependent on
      disinhibited eating behavior in adults.
AB  - STUDY OBJECTIVE: To investigate whether the relationship between short sleep
      duration and subsequent body weight gain is influenced by disinhibited eating
      behavior. DESIGN: Six-year longitudinal study. SETTING: Community setting.
      PARTICIPANTS: Two hundred seventy-six adults aged 21 to 64 years from the Quebec
      Family Study. MEASUREMENTS AND RESULTS: Body composition measurements, self
      reported sleep duration, and disinhibition eating behavior trait (Three-Factor
      Eating Questionnaire) were determined at both baseline and after 6 years. For
      each sleep-duration group (short- [<=6 h] average, [7-8 h], and long- [>=9 h]
      duration sleepers), differences in weight gain and waist circumference were
      tested by comparing the lowest (score <= 3) versus the highest (score >= 6)
      disinhibition eating behavior tertiles using analysis of covariance, with
      adjustment for potential confounding factors. Individuals having both short sleep
      duration and high disinhibition eating behavior were more likely to gain weight
      and increase their abdominal circumference over time (P<0.05); however, short
      duration sleepers having a low disinhibition eating behavior trait were not more
      likely to increase their adiposity indicators than were average-duration
      sleepers. Over the 6-year follow-up period, the incidence of overweight/obesity
      for short-duration sleepers with a high disinhibition eating behavior trait was
      2.5 times more frequent than for short-duration sleepers with a low disinhibition
      eating behavior trait. Energy intake was significantly higher in short-duration
      sleepers with a high disinhibition eating behavior trait (P<0.05 versus all other
      groups). CONCLUSIONS: We observed that having a high disinhibition eating
      behavior trait significantly increased the risk of overeating and gaining weight
      in adults characterized by short sleep duration. This observation is novel and
      might explain the interindividual differences in weight gain associated with
      short sleep duration.

PMID- 21966061
TI  - Sleep duration or bedtime? Exploring the relationship between sleep habits and
      weight status and activity patterns.
AB  - STUDY OBJECTIVES: To assess the effects of early and late bedtimes and wake up
      times on use of time and weight status in Australian school-aged children.
      DESIGN: Observational cross-sectional study involving use of time interviews and
      pedometers. SETTING: Free-living Australian adolescents. PARTICIPANTS: 2200 9- to
      16-year-olds from all states of Australia INTERVENTIONS: NA. MEASUREMENTS AND
      RESULTS: Bedtimes and wake times were adjusted for age and sex and classified as
      early or late using median splits. Adolescents were allocated into 4 sleep-wake
      pattern groups: Early-bed/Early-rise; Early-bed/Late-rise; Late-bed/Early-rise;
      Late-bed/Late-rise. The groups were compared for use of time (screen time,
      physical activity, and study-related time), sociodemographic characteristics, and
      weight status. Adolescents in the Late-bed/Late-rise category experienced 48
      min/d more screen time and 27 min less moderate-to-vigorous physical activity
      (MVPA) (P<0.0001) than adolescents in the Early-bed/Early-rise category, in spite
      of similar sleep durations. Late-bed/Late-rise adolescents had a higher BMI z
      score (0.66 vs. 0.45, P=0.0015). Late-bed/Late-rise adolescents were 1.47 times
      more likely to be overweight or obese than Early-bed/Early-rise adolescents, 2.16
      times more likely to be obese, 1.77 times more likely to have low MVPA, and 2.92
      times more likely to have high screen time. Late-bed/Late-rise adolescents were
      more likely to come from poorer households, to live in major cities, and have
      fewer siblings. CONCLUSIONS: Late bedtimes and late wake up times are associated
      with an unfavorable activity and weight status profile, independent of age, sex,
      household income, geographical remoteness, and sleep duration.

PMID- 21966062
TI  - Shared genetic background for regulation of mood and sleep: association of GRIA3
      with sleep duration in healthy Finnish women.
AB  - STUDY OBJECTIVES: Sleeping 7 to 8 hours per night appears to be optimal, since
      both shorter and longer sleep times are related to increased morbidity and
      mortality. Depressive disorder is almost invariably accompanied by disturbed
      sleep, leading to decreased sleep duration, and disturbed sleep may be a
      precipitating factor in the initiation of depressive illness. Here, we examined
      whether, in healthy individuals, sleep duration is associated with genes that we
      earlier found to be associated with depressive disorder. DESIGN: Population-based
      molecular genetic study. SETTING: Regression analysis of 23 risk variants for
      depressive disorder from 12 genes to sleep duration in healthy individuals.
      PARTICIPANTS: Three thousand, one hundred, forty-seven individuals (25-75 y) from
      population-based Health 2000 and FINRISK 2007 samples. MEASUREMENTS AND RESULTS:
      We found a significant association of rs687577 from GRIA3 on the X-chromosome
      with sleep duration in women (permutation-based corrected empirical P=0.00001,
      beta=0.27; Bonferroni corrected P=0.0052; f=0.11). The frequency of C/C genotype
      previously found to increase risk for depression in women was highest among those
      who slept for 8 hours or less in all age groups younger than 70 years. Its
      frequency decreased with the lengthening of sleep duration, and those who slept
      for 9 to 10 hours showed a higher frequency of C/A or A/A genotypes, when
      compared with the midrange sleepers (7-8 hours) (permutation-based corrected
      empirical P=0.0003, OR=1.81). CONCLUSIONS: The GRIA3 polymorphism that was
      previously found to be associated with depressive disorder in women showed an
      association with sleep duration in healthy women. Mood disorders and short sleep
      may share a common genetic background and biologic mechanisms that involve
      glutamatergic neurotransmission.

PMID- 21966063
TI  - The characteristics of sleepiness during real driving at night--a study of
      driving performance, physiology and subjective experience.
AB  - STUDY OBJECTIVES: Most studies of sleepy driving have been carried out in driving
      simulators. A few studies of real driving are available, but these have used only
      a few sleepiness indicators. The purpose of the present study was to characterize
      sleepiness in several indicators during real driving at night, compared with
      daytime driving. DESIGN: Participants drove 55 km (at 90 km/h) on a 9-m-wide
      rural highway in southern Sweden. Daytime driving started at 09:00 or 11:00 (2
      groups) and night driving at 01:00 or 03:00 (balanced design). SETTING:
      Instrumented car on a real road in normal traffic. PARTICIPANTS: Eighteen
      participants drawn from the local driving license register. INTERVENTIONS:
      Daytime and nighttime drives. MEASUREMENT AND RESULTS: The vehicle was an
      instrumented car with video monitoring of the edge of the road and recording of
      the lateral position and speed. Electroencephalography and electrooculography
      were recorded, together with ratings of sleepiness every 5 minutes. Pronounced
      effects of night driving were seen for subjective sleepiness,
      electroencephalographic indicators of sleepiness, blink duration, and speed.
      Also, time on task showed significant effects for subjective sleepiness, blink
      duration, lane position, and speed. Sleepiness was highest toward the end of the
      nighttime drive. Night driving caused a leftward shift in lateral position and a
      reduction of speed. The latter two findings, as well as the overall pattern of
      sleepiness indicators, provide new insights into the effects of night driving.
      CONCLUSION: Night driving is associated with high levels of subjective,
      electrophysiologic, and behavioral sleepiness.

PMID- 21966064
TI  - Next-day effects of ramelteon (8 mg), zopiclone (7.5 mg), and placebo on highway
      driving performance, memory functioning, psychomotor performance, and mood in
      healthy adult subjects.
AB  - STUDY OBJECTIVES: To evaluate the next-morning residual effects of ramelteon (8
      mg), zopiclone (7.5 mg), and placebo on driving performance, memory functioning,
      psychomotor performance, and mood in healthy adult subjects following bedtime
      dosing and a middle of the night awakening. DESIGN: Single-center, randomized,
      double-blind, double-dummy, placebo-controlled, crossover study. SETTING: Utrecht
      University, The Netherlands. PARTICIPANTS: 30 healthy volunteers (15 males and 15
      females). INTERVENTIONS: a single dose of ramelteon (8 mg), zopiclone (7.5 mg),
      and placebo, administered at bedtime. MEASUREMENTS: A balance test was performed
      at night. Other tests were performed the following morning, 8.5 h after
      administration. Subjects performed a 100-km highway driving test in normal
      traffic. Primary outcome measure was the standard deviation of the lateral
      position (SDLP), i.e., the weaving of the car. After driving, cognitive, memory,
      and psychomotor tests were performed and mood was assessed. RESULTS: SDLP was
      significantly increased after the intake of ramelteon (+2.2 cm) and zopiclone
      (+2.9 cm). Ramelteon and zopiclone produced significant impairment on reaction
      time (P<0.024) in the Sternberg Memory Scanning Test, slow (P<0.007) and fast
      (P<0.010) tracking, reaction speed (P<0.015) and tracking (P<0.001) in the
      Divided Attention Test, and delayed recall (P<0.032) in the Word Learning Test.
      In contrast to ramelteon, zopiclone additionally impaired performance on the
      Digit Symbol Substitution Test (P<0.001) and the balance test (P<0.001).
      CONCLUSIONS: Ramelteon (8 mg) and zopiclone (7.5 mg) significantly impaired
      driving performance, cognitive, memory, and psychomotor performance the morning
      following bedtime administration. In contrast to zopiclone, ramelteon produced no
      balance impairments. CLINICAL TRIAL IDENTIFIER: NCT00319215
      (www.clinicaltrials.gov).

PMID- 21966065
TI  - Toll-like receptor 4 is a regulator of monocyte and electroencephalographic
      responses to sleep loss.
AB  - STUDY OBJECTIVES: Sleep loss triggers changes in inflammatory signaling pathways
      in the brain and periphery. The mechanisms that underlie these changes are ill
      defined. The Toll-like receptor 4 (TLR4) activates inflammatory signaling
      cascades in response to endogenous and pathogen-associated ligands known to be
      elevated in association with sleep loss. TLR4 is therefore a possible mediator of
      some of the inflammation-related effects of sleep loss. Here we describe the
      baseline electroencephalographic sleep phenotype and the biochemical and
      electroencephalographic responses to sleep loss in TLR4-deficient mice. DESIGN,
      MEASUREMENTS AND RESULTS: TLR4-deficient mice and wild type controls were
      subjected to electroencephalographic and electromyographic recordings during
      spontaneous sleep/wake cycles and during and after sleep restriction sessions of
      3, 6, and 24-h duration, during which sleep was disrupted by an automated sleep
      restriction system. Relative to wild type control mice, TLR4-deficient mice
      exhibited an increase in the duration of the primary daily waking bout occurring
      at dark onset in a light/dark cycle. The amount of time spent in non-rapid eye
      movement sleep by TLR4-deficient mice was reduced in proportion to increased
      wakefulness in the hours immediately after dark onset. Subsequent to sleep
      restriction, EEG measures of increased sleep drive were attenuated in TLR4
      deficient mice relative to wild-type mice. TLR4 was enriched 10-fold in brain
      cells positive for the cell surface marker CD11b (cells of the monocyte lineage)
      relative to CD11b-negative cells in wild type mouse brains. To assess whether
      this population was affected selectively by TLR4 knockout, flow cytometry was
      used to count F4/80- and CD45-positive cells in the brains of sleep deprived and
      time of day control mice. While wild-type mice exhibited a significant reduction
      in the number of CD11b-positive cells in the brain after 24-h sleep restriction,
      TLR4-deficient mice did not. CONCLUSION: These data demonstrate that innate
      immune signaling pathways active in the monocyte lineage, including presumably
      microglia, detect and mediate in part the cerebral reaction to sleep loss.

PMID- 21966067
TI  - Analysis of cortical thickness in narcolepsy patients with cataplexy.
AB  - STUDY OBJECTIVES: To investigate differences in cortical thickness in narcolepsy
      patients with cataplexy and control subjects. DESIGN: Cortical thickness was
      measured using a 3-D surface-based method that enables more accurate measurement
      in deep sulci and localized regional mapping. SETTING: University hospital.
      PATIENTS AND PARTICIPANTS: We enrolled 28 patients with narcolepsy and cataplexy
      and 33 age-and sex-matched control subjects. INTERVENTIONS: Cortical thickness
      was measured using a direct method for calculating the distance between
      corresponding vertices from inner and outer cortical surfaces. MEASUREMENTS AND
      RESULTS: We normalized cortical surfaces using 2-D surface registration and
      performed diffusion smoothing to reduce the variability of folding patterns and
      to increase the power of the statistical analysis. Localized cortical thinning in
      narcolepsy patients with cataplexy was found in orbitofrontal gyri, dorsolateral
      and medial prefrontal cortexes, insula, cingulate gyri, middle and inferior
      temporal gyri, and inferior parietal lobule of the right and left hemispheres at
      the level of a false discovery rate P<0.05. No significant local increases in
      cortical thickness were observed in narcolepsy patients. A significant negative
      correlation was observed between the narcolepsy patients' scores on the Epworth
      Sleepiness Scale and the cortical thickness of the left supramarginal gyrus.
      CONCLUSIONS: Cortical thinning in narcolepsy patients with cataplexy in localized
      anatomic brain regions may serve as a possible neuroanatomic mechanism of the
      disturbances in attention, memory, emotion, and sleepiness.

PMID- 21966066
TI  - Association of sleep characteristics and cognition in older community-dwelling
      men: the MrOS sleep study.
AB  - STUDY OBJECTIVES: To examine the association of objectively and subjectively
      measured sleep characteristics with cognition in older men. DESIGN: A population
      based cross-sectional study. SETTING: 6 centers in the United States.
      PARTICIPANTS: 3,132 community-dwelling older men (mean age 76.4 +/- 5.6 years).
      INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Objectively measured sleep
      predictors from wrist actigraphy were total sleep time (TST), sleep efficiency
      (SE), and wake after sleep onset (WASO). Subjective sleep predictors were self
      reported poor sleep (Pittsburgh Sleep Quality Index [PSQI] > 5), excessive
      daytime sleepiness (EDS, Epworth Sleepiness Scale Score > 10), and TST. Cognitive
      outcomes were measured with the Modified Mini-Mental State examination (3MS), the
      Trails B test, and the Digit Vigilance Test (DVT). After adjustment for multiple
      potential confounders, WASO was modestly related to poorer cognition. Compared to
      those with WASO < 90 min, men with WASO >= 90 min took 6.1 sec longer to complete
      the Trails B test and had a 0.9-point worse 3MS score, on average (P<0.05).
      Actigraphically measured long sleepers had a slightly worse 3MS score compared to
      those with 7-8 h of sleep, but had similar Trails B and DVT completion times.
      Compared to those who self-reported sleeping 7-8 h, long sleepers (>8 h) on
      average took 8.6 sec more to complete the Trails B test, had a 0.6-point worse
      3MS score, and took 46 sec longer to complete the DVT (P<0.05). PSQI and EDS were
      not independently related to cognitive outcomes. CONCLUSIONS: There were modest
      cross-sectional associations of WASO and self-reported long sleep with cognition
      among older community-dwelling men. EDS and PSQI were not related to cognition.

PMID- 21966068
TI  - Narcolepsy with cataplexy associated with nocturnal compulsive behaviors: a case
      control study.
AB  - STUDY OBJECTIVES: To assess the prevalence of sleep related-eating disorder
      (SRED) and nocturnal smoking (NS) in patients with narcolepsy with cataplexy
      (NC). DESIGN: Case-control study. SETTING: University hospital. PATIENTS OR
      PARTICIPANTS: 65 consecutive adult NC patients (33 men; mean age 43.9 +/- 19.2
      years) and 65 age-, sex-, and geographical origin-matched controls.
      INTERVENTIONS: Validated questionnaires were used to investigate SRED, NS,
      restless legs syndrome (RLS), and psychopathological traits (using Eating
      Disorder Inventory-2 [EDI-2]; Maudsley Obsessive-Compulsive Inventory [MOCI]; and
      Beck Depression Inventory [BDI]). MEASUREMENTS AND RESULTS: NC patients showed a
      higher prevalence of SRED (32% vs 3%, P=0.00001), NS (21% vs 0%, P=0.00006), and
      RLS (18% vs 5%, P=0.013) than controls. Moreover, NC patients presented more
      frequently with an eating-related pathological profile on the EDI-2 (80% vs 46%,
      P=0.00006) and had a higher prevalence of depressed mood on the BDI (41% vs 18%,
      P=0.004). In comparison to patients without SRED, NC patients with SRED were more
      frequently women (71% vs 39%, P=0.013), had higher "bulimic" (29% vs 2%, P=0.004)
      and "social insecurity" (48% vs 18%, P=0.013) traits on the EDI-2, had higher
      obsessive-compulsiveness on the MOCI (29% vs 4%, P = 0.009), and were more
      depressed on the BDI (67% vs 29%, P=0.005). NC patients with NS showed more
      frequent pathological profiles on the EDI-2 (100% vs 75%, P=0.035), including the
      "bulimic" (29% vs 6%, P=0.015), "perfectionism" (43% vs 14%, P=0.016), and
      "social insecurity" (50% vs 22, P=0.035) profiles. CONCLUSION: Our study shows a
      strong association of the compulsive nocturnal behaviors SRED and NS with adult
      NC.

PMID- 21966069
TI  - The role of infant sleep in intergenerational transmission of trauma.
AB  - INTRODUCTION: Children of parents who experienced trauma often present emotional
      and behavioral problems, a phenomenon named inter-generational transmission of
      trauma (IGTT). Combined with antenatal factors, parenting and the home
      environment contribute to the development and maintenance of sleep problems in
      children. In turn, infant sleep difficulty predicts behavioral and emotional
      problems later in life. The aim of this study was to investigate whether infant
      sleep problems predict early behavioral problems indicative of IGTT. METHODS: 184
      first-time mothers (ages 18-47) participated. N=83 had a history of childhood
      abuse and posttraumatic stress disorder (PTSD+); 38 women reported childhood
      abuse but did not meet diagnostic criteria for PTSD (PTSD-); and the control
      group (N=63) had neither a history of abuse nor psychopathology (CON).
      Depression, anxiety, and sleep difficulty were assessed in the mothers at 4
      months postpartum. Infant sleep was assessed using the Child Behavior Sleep
      Questionnaire (CSHQ). Outcome measures included the Parent Bonding Questionnaire
      (PBQ) at 4 months and the Child Behavior Check List (CBCL) at 18 months. RESULTS:
      Infants of PTSD+ mothers scored higher on the CSHQ and had more separation
      anxiety around bedtime than PTSD- and CON, and the severity of their symptoms was
      correlated with the degree of sleep disturbance. Maternal postpartum depression
      symptoms mediated impaired mother-infant bonding, while infant sleep disturbance
      contributed independently to impaired bonding. Mother-infant bonding at 4 months
      predicted more behavioral problems at 18 months. CONCLUSIONS: Infant sleep
      difficulties and maternal mood play independent roles in infant-mother bonding
      disturbance, which in turn predicts behavioral problems at 18 months.

PMID- 21966070
TI  - Sleep EEG provides evidence that cortical changes persist into late adolescence.
AB  - STUDY OBJECTIVES: To examine developmental changes in the human sleep
      electroencephalogram (EEG) during late adolescence. SETTING: A 4-bed sleep
      laboratory. PARTICIPANTS: Fourteen adolescents (5 boys) were studied at ages 15
      or 16 (initial) and again at ages 17 to 19 (follow-up). INTERVENTIONS: N/A.
      MEASUREMENTS AND RESULTS: All-night polysomnography was recorded at each
      assessment and scored according to the criteria of Rechtschaffen and Kales. A 27%
      decline in duration of slow wave sleep, and a 22% increase of stage 2 sleep was
      observed from the initial to the follow-up session. All-night spectral analysis
      of 2 central and 2 occipital leads revealed a significant decline of NREM and REM
      sleep EEG power with increasing age across frequencies in both states. Time
      frequency analysis revealed that the decline in power was consistent across the
      night for all bands except the delta band. The decreases in power were most
      pronounced over the left central (C3/A2) and right occipital (O2/A1) derivations.
      CONCLUSIONS: Using longitudinal data, we show that the developmental changes to
      the sleeping EEG that begin in early adolescence continue into late adolescence.
      As with early adolescents, we observed hemispheric asymmetry in the decline of
      sleep EEG power. This decline was state and frequency nonspecific, suggesting
      that it may be due to the pruning of synapses known to occur during adolescence.

PMID- 21966071
TI  - Longitudinal course and outcome of chronic insomnia in Hong Kong Chinese
      children: a 5-year follow-up study of a community-based cohort.
AB  - OBJECTIVES: There are limited data on the long-term outcome of childhood
      insomnia. We explored the longitudinal course, predictors, and impact of
      childhood insomnia in a community-based cohort. DESIGN: 5-year prospective follow
      up. SETTING: Community-based. PARTICIPANTS: 611 children (49% boys) aged 9.0 +/-
      1.8 years at baseline; 13.7 +/- 1.8 years at follow-up. INTERVENTION: NA. MAIN
      EXPOSURES: Chronic insomnia was defined as difficulty initiating sleep,
      difficulty maintaining sleep and/or early morning awakening >= 3 times/week in
      the past 12 months. OUTCOME MEASURES: General health, upper airway inflammatory
      diseases, and behavioral problems in recent one year were assessed at both time
      points, while mental health and lifestyle practice were assessed at follow-up
      study. The questionnaires at baseline and follow-up were reported by
      parents/caretakers and adolescents themselves, respectively. RESULTS: The
      prevalence of chronic insomnia was 4.2% and 6.6% for baseline and follow-up,
      respectively. The incidence and persistence rates of chronic insomnia were 6.2%
      and 14.9%, respectively. New incidence of insomnia was associated with lower
      paternal education level, baseline factors of frequent temper outbursts and
      daytime fatigue as well as alcohol use and poor mental health at follow-up.
      Baseline chronic medical disorders, frequent temper outbursts, and poor mental
      health at follow-up were associated with the persistence of insomnia in
      adolescents. Baseline insomnia was associated with frequent episodes of
      laryngopharyngitis and lifestyle practice (coffee and smoking) at follow-up.
      CONCLUSIONS: Chronic insomnia is a common problem with moderate persistent rate
      in children. The associations of adverse physical and mental health consequences
      with maladaptive lifestyle coping (smoking and alcohol) argue for rigorous
      intervention of childhood insomnia.

PMID- 21966072
TI  - Cross-lagged relationships between workplace demands, control, support, and sleep
      problems.
AB  - STUDY OBJECTIVES: Sleep problems are experienced by a large part of the
      population. Work characteristics are potential determinants, but limited
      longitudinal evidence is available to date, and reverse causation is a plausible
      alternative. This study examines longitudinal, bidirectional relationships
      between work characteristics and sleep problems. DESIGN: Prospective cohort/two
      wave panel. SETTING: Sweden. PARTICIPANTS: 3065 working men and women
      approximately representative of the Swedish workforce who responded to the 2006
      and 2008 waves of the Swedish Longitudinal Occupational Survey of Health (SLOSH).
      INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Bidirectional relationships
      between, on the one hand, workplace demands, decision authority, and support,
      and, on the other hand, sleep disturbances (reflecting lack of sleep continuity)
      and awakening problems (reflecting feelings of being insufficiently restored),
      were investigated by structural equation modeling. All factors were modeled as
      latent variables and adjusted for gender, age, marital status, education, alcohol
      consumption, and job change. Concerning sleep disturbances, the best fitting
      models were the "forward" causal model for demands and the "reverse" causal model
      for support. Regarding awakening problems, reciprocal models fitted the data
      best. CONCLUSIONS: Cross-lagged analyses indicates a weak relationship between
      demands at Time 1 and sleep disturbances at Time 2, a "reverse" relationship from
      support T1 to sleep disturbances T2, and bidirectional associations between work
      characteristics and awakening problems. In contrast to an earlier study on
      demands, control, sleep quality, and fatigue, this study suggests reverse and
      reciprocal in addition to the commonly hypothesized causal relationships between
      work characteristics and sleep problems based on a 2-year time lag.

PMID- 21966073
TI  - Fast and slow spindles during the sleep slow oscillation: disparate coalescence
      and engagement in memory processing.
AB  - STUDY OBJECTIVES: Thalamo-cortical spindles driven by the up-state of neocortical
      slow (< 1 Hz) oscillations (SOs) represent a candidate mechanism of memory
      consolidation during sleep. We examined interactions between SOs and spindles in
      human slow wave sleep, focusing on the presumed existence of 2 kinds of spindles,
      i.e., slow frontocortical and fast centro-parietal spindles. DESIGN: Two
      experiments were performed in healthy humans (24.5 +/- 0.9 y) investigating
      undisturbed sleep (Experiment I) and the effects of prior learning (word paired
      associates) vs. non-learning (Experiment II) on multichannel EEG recordings
      during sleep. MEASUREMENTS AND RESULTS: Only fast spindles (12-15 Hz) were
      synchronized to the depolarizing SO up-state. Slow spindles (9-12 Hz) occurred
      preferentially at the transition into the SO down-state, i.e., during waning
      depolarization. Slow spindles also revealed a higher probability to follow rather
      than precede fast spindles. For sequences of individual SOs, fast spindle
      activity was largest for "initial" SOs, whereas SO amplitude and slow spindle
      activity were largest for succeeding SOs. Prior learning enhanced this pattern.
      CONCLUSIONS: The finding that fast and slow spindles occur at different times of
      the SO cycle points to disparate generating mechanisms for the 2 kinds of
      spindles. The reported temporal relationships during SO sequences suggest that
      fast spindles, driven by the SO up-state feed back to enhance the likelihood of
      succeeding SOs together with slow spindles. By enforcing such SO-spindle cycles,
      particularly after prior learning, fast spindles possibly play a key role in
      sleep-dependent memory processing.

PMID- 21966074
TI  - NREM sleep stage transitions control ultradian REM sleep rhythm.
AB  - STUDY OBJECTIVES: The cyclic sequence of NREM and REM sleep, the so-called
      ultradian rhythm, is a highly characteristic feature of sleep. However, the
      mechanisms responsible for the ultradian REM sleep rhythm, particularly in
      humans, have not to date been fully elucidated. We hypothesize that a stage
      transition mechanism is involved in the determination of the ultradian REM sleep
      rhythm. PARTICIPANTS: Ten healthy young male volunteers (AGE: 22 +/- 4 years,
      range 19-31 years) spent 3 nights in a sleep laboratory. The first was the
      adaptation night, and the second was the baseline night. On the third night, the
      subjects received risperidone (1 mg tablet), a central serotonergic and
      dopaminergic antagonist, 30 min before the polysomnography recording.
      MEASUREMENTS AND RESULTS: We measured and investigated transition probabilities
      between waking, REM, and NREM sleep stages (N1, N2, and N3) within the REM-onset
      intervals, defined as the intervals between the onset of one REM period and the
      beginning of the next, altered by risperidone. We also calculated the transition
      intensity (i.e., instantaneous transition rate) and examined the temporal pattern
      of transitions within the altered REM-onset intervals. We found that when the REM
      onset interval was prolonged by risperidone, the probability of transitions from
      N2 to N3 was significantly increased within the same prolonged interval, with a
      significant delay and/or recurrences of the peak intensity of transitions from N2
      to N3. CONCLUSIONS: These results suggest that the mechanism governing NREM sleep
      stage transitions (from light to deep sleep) plays an important role in
      determining ultradian REM sleep rhythms.

PMID- 21966076
TI  - A SPECT Camera for Combined MRI and SPECT for Small Animals.
AB  - We describe an MR-compatible SPECT camera for small animals. The SPECT camera
      system can be inserted into the bore of a state-of-the-art MRI system and allows
      researchers to acquire tomographic images from a mouse in-vivo with the MRI and
      the SPECT acquiring simultaneously. The SPECT system provides functional
      information, while MRI provides anatomical information. Until today it was
      impossible to operate conventional SPECT inside the MRI because of mutual
      interference. The new SPECT technology is based on semiconductor radiation
      sensors (CZT, ASICs), and it fits into conventional high field MRI systems with a
      minimum 12-cm bore size. The SPECT camera has an MR-compatible multi-pinhole
      collimator for mice with a o25-mm field-of-view. For the work reported here we
      assembled a prototype SPECT camera system and acquired SPECT and MRI data from
      radioactive sources and resolution phantoms using the camera outside and inside
      the MRI.

PMID- 21966075
TI  - Efficacy and safety of doxepin 3 and 6 mg in a 35-day sleep laboratory trial in
      adults with chronic primary insomnia.
AB  - STUDY OBJECTIVES: To evaluate the efficacy and safety of doxepin (DXP) 3 mg and 6
      mg in adults diagnosed with primary insomnia. DESIGN AND METHODS: The study was a
      randomized, double-blind, parallel-group, placebo-controlled trial. Patients
      meeting DSM-IV-TR criteria for primary insomnia were randomized to 35 days of
      nightly treatment with DXP 3 mg (n=75), DXP 6 mg (n=73), or placebo (PBO; n=73),
      followed by 2 nights of single-blind PBO to evaluate discontinuation (DC)
      effects. Efficacy was assessed using polysomnography (PSG) and patient reports.
      Efficacy data were examined for Night (N) 1, N15, and N29. Safety assessments
      were conducted throughout the study. RESULTS: Compared with PBO, DXP 3 and 6 mg
      significantly improved wake time after sleep onset (WASO) on N1 (3 mg and 6 mg;
      P<0.0001), N15 (3 mg P=0.0025; 6 mg P=0.0009), and N29 (3 mg P=0.0248; 6 mg
      P=0.0009), latency to persistent sleep (LPS) on N1 (3 mg P=0.0047; 6 mg
      P=0.0007), and total sleep time (TST) on N1 (3 mg and 6 mg P<0.0001), N15 (6 mg
      P=0.0035), and N29 (3 mg P=0.0261; 6 mg P<0.0001). In terms of early morning
      awakenings, DXP 3 and 6 mg demonstrated significant improvements in SE in the
      final quarter of the night on N1, N15, and N29, with the exception of 3 mg on N29
      (P=0.0691). Rates of discontinuation were low, and the safety profiles were
      comparable across the 3 treatment groups. There were no significant next-day
      residual effects, and there were no spontaneous reports of memory impairment,
      complex sleep behaviors, anticholinergic effects, weight gain, or increased
      appetite. Additionally, there was no evidence of rebound insomnia after DXP
      discontinuation. CONCLUSIONS: Five weeks of nightly administration of DXP 3 mg
      and 6 mg to adults with chronic primary insomnia resulted in significant and
      sustained improvements in sleep maintenance and early morning awakenings (with
      the exception of SE in the final quarter of the night on N29 for 3 mg
      [P=0.0691]). These sleep improvements were not accompanied by next-day residual
      effects or followed by rebound insomnia or withdrawal effects upon
      discontinuation. These findings confirm the unique profile of sleep maintenance
      efficacy and safety of DXP observed in prior studies.

PMID- 21966077
TI  - Long-Term Implications of Welfare Reform for the Development of Adolescents and
      Young Adults.
AB  - We draw upon the 3-wave longitudinal dataset called Welfare Children and
      Families: A Three-City Study to examine the long-term implications for
      adolescents and young adults (N=783) of mothers' welfare receipt and labor force
      participation from 1999 to 2005. In general, changes in mothers' work and welfare
      patterns were not associated with deterioration or improvement in youth
      development (ages 16 to 20 years at wave 3). The few significant associations
      suggested that youth whose mothers increased employment (net of welfare
      participation) were more likely to show declines in serious behavior problems and
      delinquency compared to youth whose mothers were unemployed or employed part-time
      during the study period. Welfare roll exits (controlling for employment
      experiences) were unrelated to adolescent and young adult outcomes. Mothers'
      employment transitions were linked to improvements in household income and
      mothers' self esteem in addition to reductions in financial strain and their own
      illegal activities. However, these associations did not explain the relation
      between maternal employment and youths' improved behavior. These results do not
      support the predictions of either the supporters or the opponents of welfare
      reform, an outcome we discuss.

PMID- 21966078
TI  - MULTISCALE MODELING OF PSEUDOMONAS AERUGINOSA SWARMING.
AB  - Experiments have shown that wild type P. aeruginosa swarms much faster than rhlAB
      mutants on 0.4% agar concentration surface. These observations imply that
      development of a liquid thin film is an important component of the self-organized
      swarming process. A multiscale model is presented in this paper for studying
      interplay of key hydrodynamical and biological mechanisms involved in the
      swarming process of P. aeruginosa. This model combines a liquid thin film
      equation, convection-reaction-diffusion equations and a cell-based stochastic
      discrete model. Simulations demonstrate how self-organized swarming process based
      on the microscopic individual bacterial behavior results in complicated fractal
      type patterns at macroscopic level. It is also shown that quorum sensing
      mechanism causing rhamnolipid synthesis and resulting liquid extraction from the
      substrate lead to the fast swarm expansion. Simulations also demonstrate
      formation of fingers (tendrils) at the edge of a swarm which have been earlier
      observed in experiments.

PMID- 21966079
TI  - The 20-Year Trajectory of Marital Quality in Enduring Marriages: Does Equity
      Matter?
AB  - I examine the trajectory of marital quality as a function of relationship equity
      with data from a six-wave panel study of 704 married respondents between 1980 and
      2000. Reporting that one "gives more" to the marriage (subjective underbenefit)
      is more likely for women than men at any given marital duration. Respondent's
      relative contribution to income, paid labor, housework, and health (objective
      underbenefit) raises this probability for women of average religiosity. For the
      more religious, objective underbenefit has no effect on women's sense of
      underbenefit, but reduces men's sense of underbenefit. Objective underbenefit
      lowers women's, but raises men's, marital quality, at any marital duration. The
      relevance of equity was not diluted by the passage of time in marriage.

PMID- 21966080
TI  - Physician-diagnosed respiratory conditions and mental health symptoms 7-9 years
      following the World Trade Center disaster.
AB  - BACKGROUND: This study examines the prevalence of physician-diagnosed respiratory
      conditions and mental health symptoms in firefighters and emergency medical
      service workers up to 9 years after rescue/recovery efforts at the World Trade
      Center (WTC). METHODS: We analyzed Fire Department of New York (FDNY) physician
      and self-reported diagnoses by WTC exposure and quintiles of pulmonary function
      (FEV1% predicted). We used screening instruments to assess probable post
      traumatic stress disorder (PTSD) and probable depression. RESULTS: FDNY
      physicians most commonly diagnosed asthma (8.8%) and sinusitis (9.7%). The
      highest prevalence of physician-diagnosed obstructive airway disease (OAD) was in
      the lowest FEV1% predicted quintile. Participants who arrived earliest on 9/11
      were more likely to have physician-diagnosed asthma (OR = 1.4). Seven percent had
      probable PTSD. 19.4% had probable depression. CONCLUSIONS: Self-reported and
      physician-diagnosed respiratory conditions remain common, especially among those
      who arrived earliest at the WTC site. OAD was associated with the lowest
      pulmonary function. Since respiratory and mental health conditions remain
      prevalent, ongoing monitoring and treatment is important.

PMID- 21966081
TI  - Attention Problems Mediate the Association between Severity of Physical Abuse and
      Aggressive Behavior in a Sample of Maltreated Early Adolescents.
AB  - Empirical evidence has accumulated documenting an association between childhood
      physical abuse and aggressive behavior. Relatively fewer studies have explored
      possible mediating mechanisms that may explain this association. The purpose of
      the current study was to examine whether caregiver- and youth-reported attention
      problems mediate the association between physical abuse severity and aggressive
      behavior. A sample of 240 maltreated early adolescents (ages 9-11) and their
      caregivers were interviewed within 14 months of being removed from the home.
      Results from multiple regression analyses indicated that caregiver- and youth
      reported attention problems were partial mediators of the association between
      physical abuse severity and aggressive behavior. These associations were
      significant even after controlling for children's intellectual functioning, sex,
      age, and severity of other maltreatment types. Possible explanations for the
      detrimental impact of physical abuse on behavior are discussed, along with the
      implications of the current study's results for interventions aimed at reducing
      early adolescent aggressive behavior.

PMID- 21966083
TI  - Generalized Markov Models of Infectious Disease Spread: A Novel Framework for
      Developing Dynamic Health Policies.
AB  - We propose a class of mathematical models for the transmission of infectious
      diseases in large populations. This class of models, which generalizes the
      existing discrete-time Markov chain models of infectious diseases, is compatible
      with efficient dynamic optimization techniques to assist real-time selection and
      modification of public health interventions in response to evolving
      epidemiological situations and changing availability of information and medical
      resources. While retaining the strength of existing classes of mathematical
      models in their ability to represent the within-host natural history of disease
      and between-host transmission dynamics, the proposed models possess two
      advantages over previous models: (1) these models can be used to generate optimal
      dynamic health policies for controlling spreads of infectious diseases, and (2)
      these models are able to approximate the spread of the disease in relatively
      large populations with a limited state space size and computation time.

PMID- 21966084
TI  - Electric field and grain size dependence of Meyer-Neldel energy in C(60) films.
AB  - Meyer-Neldel rule for charge carrier mobility measured in C(60)-based organic
      field-effect transistors (OFETs) at different applied source drain voltages and
      at different morphologies of semiconducting fullerene films was systematically
      studied. A decrease in the Meyer-Neldel energy E(MN) from 36 meV to 32 meV was
      observed with changing electric field in the channel. Concomitantly a decrease
      from 34 meV to 21 meV was observed too by increasing the grain size and the
      crystallinity of the active C(60) layer in the device. These empiric findings are
      in agreement with the hopping-transport model for the temperature dependent
      charge carrier mobility in organic semiconductors with a Gaussian density of
      states (DOS). Experimental results along with theoretical descriptions are
      presented.

PMID- 21966089
TI  - ?

PMID- 21966091
TI  - Own and Others' Prior Experiences Influence Children's Imitation of Causal Acts.
AB  - Young children learn from others' examples, and they do so selectively. We
      examine whether the efficacy of prior experiences influences children's
      imitation. Thirty-six-month-olds had initial experience on a causal learning task
      either by performing the task themselves or by watching an adult perform it. The
      nature of the experience was manipulated such that the actor had either an easy
      or a difficult experience completing the task. Next, a second adult demonstrated
      an innovative technique for completing it. Children who had a difficult first
      person experience, and those who had witnessed another person having difficulty,
      were significantly more likely to adopt and imitate the adult's innovation than
      those who had or witnessed an easy experience. Children who observed another were
      also more likely to imitate than were those who had the initial experience
      themselves. Imitation is influenced by prior experience, both when it is obtained
      through one's own hands-on motor manipulation and when it derives from observing
      the acts of others.

PMID- 21966092
TI  - Exhaustive glycosylation, PEGylation, and glutathionylation of a [G4]-ene(48)
      dendrimer via photoinduced thiol-ene coupling.
AB  - We report in this paper the use of free-radical thiol-ene coupling (TEC) for the
      introduction of carbohydrate, poly(ethylene glycol), and peptide fragments at the
      periphery of an alkene functional dendrimer. Four different sugar thiols
      including glucose, mannose, lactose and sialic acid, two PEGylated thiols and the
      natural tripeptide glutathione were reacted with a fourth generation alkene
      functional dendrimer [G4]-ene(48) upon irradiation at lambda(max) 365 nm. In all
      cases, the (1)H NMR spectra of the crude reaction mixture revealed the complete
      disappearance of alkene proton signals indicating the quantitative conversion of
      all 48 alkene groups of the dendrimer. With one exception only, all dendrimer
      conjugates were isolated in high yields (70-94%), validating the high efficiency
      of multiple TEC reactions on a single substrate. All isolated and purified
      compounds were analyzed by MALDI-TOF spectrometry and gave spectra consistent
      with the assigned structure.

PMID- 21966093
TI  - Poly(allyl glycidyl ether)-A versatile and functional polyether platform.
AB  - Allyl glycidyl ether, polymerized from potassium alkoxide/naphthalenide
      initiators under both neat and solution conditions was shown to be a highly
      controlled process. In both cases, molar masses (10-100 kg/mol) were determined
      by the reaction stoichiometry, and low polydispersity indices (1.05-1.33) could
      be obtained with a full understanding of the dominant side reaction,
      isomerization of the allyl side chain, being developed. The degree of
      isomerization of allyl to cis-prop-1-enyl ether groups (0 - 10 % mol.) was not
      correlated to the molar mass or polydispersity of the polymer but was dictated by
      the polymerization temperature. This allows the extent of isomerization to be
      reduced to essentially zero under either melt or solution conditions at
      polymerization temperatures of less than 40  degrees C.

PMID- 21966094
TI  - Functional activation for imitation of seen and heard speech.
AB  - This study examined fMRI activation when perceivers either passively observed or
      observed and imitated matched or mismatched audiovisual ("McGurk") speech
      stimuli. Greater activation was observed in the inferior frontal gyrus (IFG)
      overall for imitation than for perception of audiovisual speech and for imitation
      of the McGurk-type mismatched stimuli than matched audiovisual stimuli. This
      unique activation in the IFG during imitation of incongruent audiovisual speech
      may reflect activation associated with direct matching of incongruent auditory
      and visual stimuli or conflict between category responses. This study provides
      novel data about the underlying neurobiology of imitation and integration of AV
      speech.

PMID- 21966095
TI  - Single-Molecule Force Spectroscopy of DNA-Based Reversible Polymer Bridges:
      Surface Robustness and Homogeneity.
AB  - Single-molecule force spectroscopy, as implemented in an atomic force microscope,
      provides a rarely-used method by which to monitor dynamic processes that occur
      near surfaces. Here, a methodology is presented and characterized that
      facilitates the study of polymer bridging across nanometer-sized gaps. The model
      system employed is that of DNA-based reversible polymers, and an automated
      procedure is introduced that allows the AFM tip-surface contact point to be
      automatically determined, and the distance d between opposing surfaces to be
      actively controlled. Using this methodology, the importance of several
      experimental parameters was systematically studied, e.g. the frequency of
      repeated tip/surface contacts, the area of the substrate surface sampled by the
      AFM, and the use of multiple AFM tips and substrates. Experiments revealed the
      surfaces to be robust throughout pulling experiments, so that multiple touches
      and pulls could be carried out on a single spot with no measurable affect on the
      results. Differences in observed bridging probabilities were observed, both on
      different spots on the same surface and, more dramatically, from one day to
      another. Data normalization via a reference measurement allows data from multiple
      days to be directly compared.

PMID- 21966096
TI  - Prepubertal unilateral gynecomastia: a report of two cases.
AB  - BACKGROUND: Gynecomastia is defined as the presence of excessive breast tissue in
      males, which can appear unilateral or bilateral. Bilateral gynecomastia is
      frequently found in the neonatal period, early in puberty, and with increasing
      age. Prepubertal unilateral gynecomastia in the absence of endocrine
      abnormalities is extremely rare, with only a few cases in literature.  METHODS:
      We report the cases of two otherwise healthy boys of 8 and 11 years old with
      unilateral breast masses. No abnormalities were found on ultrasonography and all
      endocrine parameters were within normal limits. Treatment consisted of peripheral
      liposuction followed by subcutaneous partial resection of the gland, conducted
      through an infra-areolar incision.  RESULTS: Microscopy of the subcutaneous
      mastectomy specimen revealed gynecomastia without signs of malignancy.
      Postoperative course of both patients was uncomplicated, with no signs of
      recurrence of breast tissue.  CONCLUSIONS: Atypical presentations of gynecomastia
      are often not recognized, with little attention to breast development in
      prepubertal non-obese children. Since prepubertal gynecomastia could be a sign of
      possible underlying diseases, a thorough examination and further research is
      recommended. If there is no causal treatment, surgical resection is the therapy
      of first choice. Peripheral liposuction and surgical resection of the gland
      tissue are the mainstay of treatment. In summary, we describe two cases of
      prepubertal unilateral gynecomastia with a normal endocrine workup. Further
      research is needed to establish the pathophysiologic mechanisms of prepubertal
      gynecomastia, since underlying etiology in most cases remains unclear.

PMID- 21966097
TI  - A facile method for synthesis of polyaniline nanospheres and effect of doping on
      their electrical conductivity.
AB  - The synthesis of polyaniline (PANI) nanospheres by a simple template-free method
      has been described. The polymerization of aniline in aqueous medium was
      accomplished using ammonium persulfate without any protonic acid. The UV-vis
      spectrum of PANI nanospheres displayed the characteristic absorption peak of pi
      pi* transition of the benzenoid ring at 355 nm. The oxidation state of PANI
      nanospheres was identified with FT-IR spectroscopy by comparing the two bands at
      1582 (ring stretching in quinoid unit) and 1498 cm(-1) (ring stretching in
      bezenoid unit). The X-ray diffraction patterns demonstrated the low crystalline
      nature of PANI nanospheres. The morphology of PANI nanospheres was spherical and
      the mean diameter of nanospheres was found in the range of 3-12 nm. The thermal
      behavior of PANI nanospheres was studied by thermogravimetric analysis. The
      effect of doping of HCl and H(2)SO(4) on PANI nanospheres was studied by
      measuring the current as a function of time of exposure. The high electrical
      conductivity of 6*10(-2) S cm(-1) was obtained for PANI nanospheres at their
      optimum doping state by 100 ppm HCl.

PMID- 21966098
TI  - Cultural Adaptations: A Complex Interplay between Clinical and Cultural Issues.
AB  - Psychotherapy is a Western method of treating mental illness. Culturally adapting
      psychotherapy to better meet the needs of ethnic minorities is an important
      endeavor. Hall et al. (2011) did an excellent job of reviewing the intersection
      and divergence between Asian culture and mindfulness and acceptance-based
      therapies. They also point out that some therapies can be naturally syntonic with
      Asian American cultural values and belief systems. This is especially important
      given cultural differences between the East and West. Below, I provide an
      overview of the complexities involved in adapting treatments for diverse clients.
      I also discuss the importance of deconstructing stereotypes and understanding the
      complex interplay between clinical and cultural issues. Individualization of
      treatment for diverse clients can be achieved through culturally formed practice.

PMID- 21966099
TI  - Structure reactivity relationship in the reaction of DNA guanyl radicals with
      hydroxybenzoates.
AB  - In DNA, guanine bases are the sites from which electrons are most easily removed.
      As a result of hole migration to this stable location on guanine, guanyl radicals
      are major intermediates in DNA damage produced by the direct effect of ionizing
      radiation (ionization of the DNA itself and not through the intermediacy of water
      radicals). We have modeled this process by employing gamma irradiation in the
      presence of thiocyanate ions, a method which also produces single electron
      oxidized guanyl radicals in plasmid DNA in aqueous solution. The stable products
      formed in DNA from these radicals are detected as strand breaks after incubation
      with the FPG protein. When a phenolic compound is present in solution during
      gamma irradiation, the formation of guanyl radical species is decreased by
      electron donation from the phenol to the guanyl radical. We have quantified the
      rate of this reaction for four different phenolic compounds bearing carboxylate
      substituents as proton acceptors. A comparison of the rates of these reactions
      with the redox strengths of the phenolic compounds reveals that salicylate reacts
      ca. 10-fold faster than its structural analogs. This observation is consistent
      with a reaction mechanism involving a proton coupled electron transfer, because
      intra-molecular transfer of a proton from the phenolic hydroxyl group to the
      carboxylate group is possible only in salicylate, and is favored by the strong 6
      membered ring intra-molecular hydrogen bond in this compound.

PMID- 21966100
TI  - Fascinating potential of aspergilli.

PMID- 21966101
TI  - Molecular basis of cystic fibrosis disease: an Indian perspective.
AB  - Cystic fibrosis is a common autosomal recessive disorder usually found in
      population of white Caucasian descent. Now it is well documented the presence of
      CF disease in India with the advancement of laboratory testing. As once it was
      thought non existence of this disease in our population. Most of the phenotype of
      CF disease was in accordance of western population. Genetic analysis of CFTR gene
      in Indian CF patients revealed that most common mutation was delta F508 mutation.
      However, it was less than Caucasian population. CFTR mutations are also a
      causative factor in the pathogenesis of male infertility due to obstructive
      azoospermia. There are two most common mutation viz. IVS8-T5 and delta F508 which
      are responsible for congenital absence of vas deferens in male infertility
      patients. Elevated levels of sweat chloride at two occasions along with the
      presence of two mutations in CFTR gene was gold standard method for diagnosis of
      CF disease. It is noteworthy here that due to magnitude of Indian population, the
      total CF disease load would be more than many European countries. Clinical data
      demonstrate the prevalence of both classical and genetic form of CF in India.

PMID- 21966102
TI  - Association of Pro/Anti-inflammatory Cytokine Gene Polymorphisms with Benign
      Prostate Hyperplasia Risk.
AB  - Benign prostate hyperplasia (BPH) is a common condition in aged men and result
      from prolong chronic inflammation in prostate gland. Cytokines are important
      molecules responsible for inflammation. Single nucleotide polymorphisms (SNPs) in
      promoter region of cytokine genes have been shown to alter the level of
      cytokines. Hence we evaluated the association of pro-inflammatory and anti
      inflammatory cytokine SNPs in a North Indian cohort of BPH patients. We observed
      that IL-1B -511 CT + TT genotypes conferred protective effect for susceptibility
      to BPH (OR 0.39, P 0.001). Our results also demonstrated that TNF-A -1031 C
      allele to be associated with risk for BPH (OR 1.89, P < 0.0001). Moreover, we
      also observed twofold risk for IL-10 -1082 cytokine gene polymorphism (OR 1.96, P
      0.048). No association was observed with risk of BPH for IFN-G +874, IL-1 RN
      VNTR, IL-6 -174, IL-10 -819 and TGF-B +28. Our findings of IL-1B -511, TNF-A 
      1031 and IL-10 -1082 suggested that these variants play important role in
      susceptibility to BPH. Future studies in large cohort of different ethnicity BPH
      groups are warranted to establish definite associations with other cytokine gene
      polymorphisms as well.

PMID- 21966103
TI  - Protective Role of Catechin on d-Galactosamine Induced Hepatotoxicity Through a
      p53 Dependent Pathway.
AB  - Objective of this study was to obtain a better understanding of the mechanism
      responsible for the d-galactosamine (d-GalN) induced hepatotoxicity and to study
      the effect of catechin against d-GalN induced hepatotoxicity. Catechin 50 and 100
      mg/kg b.wt was administered for 1 week by oral route. Liver damage was induced by
      intra-peritoneal administration of 400 mg/kg b.wt d-galactosamine on the last day
      of catechin treatment. At the end of treatment all animals were killed and liver
      enzyme levels were estimated. Dissected hepatic samples were used for
      histopathology, RNA isolation, expression studies of Bax, Bcl-2 and p53 mRNA
      levels and mitochondrial membrane potential studies. We found that increases in
      the liver enzyme activity and decrease in antioxidant enzyme activity by d-GalN
      were significantly restricted by oral pretreatment with catechin. Disruption of
      mitochondrial membrane potential, up regulation of p53, Bax and down regulation
      of Bcl-2 mRNA levels in the liver of d-GalN intoxicated rats were effectively
      prevented by pretreatment with catechin.

PMID- 21966104
TI  - Effect of isoproterenol on tissue defense enzymes, hemodynamic and left
      ventricular contractile function in rats.
AB  - Present study investigated the effects of isoproterenol-induced oxidative stress
      on hemodynamic and ventricular functions in rats. Subcutaneous injections of
      isoproterenol (85 mg/kg for two consecutive days at 24 h interval) significantly
      decreased myocardial antioxidant enzymes; superoxide dismutase, catalase and
      glutathione peroxidase in heart. Isoproterenol-induced oxidative stress was also
      evidenced by significant depletion of reduced glutathione and increased formation
      of lipid peroxidation product, thiobarbituric acid reactive substances along with
      depletion of myocyte injury specific marker enzymes; creatine phosphokinase
      isoenzyme and lactate dehydrogenase. The deleterious outcome of oxidative stress
      on hemodyanmic parameters and ventricular function were further evidenced by
      decreased systolic, diastolic and mean arterial blood pressure, heart rate,
      ventricular contractility; [(+)LVdP/dt] and relaxation; [(-)LVdP/dt], along with
      an increased left ventricular end diastolic pressure (LVEDP). Subsequent to
      changes in heart rate and arterial pressure, isoproterenol also decreased rate
      pressure product. Present study findings clearly demonstrate the detrimental
      outcome of isoproterenol induced-oxidative stress on cardiac function and tissue
      antioxidant defense and substantiate its suitability as an animal model for the
      evaluation of cardioprotective agents.

PMID- 21966105
TI  - Effect of Certain Antibiotics Against Filarial Parasite Brugia malayi In Vitro:
      Possible Role of Oxidative Stress.
AB  - WHO-Tropical Disease Research scheme highlighted the need for development of new
      anti-filarial drugs. Certain antibiotics have recently been found effective
      against Wolbachia, co-existing symbiotically with filarial parasites.
      Inflammatory response entails oxidative mechanism to educe direct anti-microbial
      effect. In the present study microfilariae were maintained in vitro in medium
      supplemented with varying concentrations of tetracycline, doxycycline (20-100
      MUg/ml) or ciprofloxacin (50-250 MUg/ml) separately to find out any involvement
      of oxidative mechanism in the anti-filarial effect of these antibiotics. Loss of
      motility of the microfilariae was measured after 48 h and correlated with the
      levels of MDA, nitric oxide and protein-carbonylation. Significant loss of
      microfilarial motility was recorded with increasing concentration of tetracycline
      and doxycycline but with ciprofloxacin the effect was not marked. Agents with
      high antifilarial activity revealed significant association with oxidative
      parameters in a dose dependent manner. The result suggests that oxidative effect
      might be exploited to design novel antifilarial drug candidate.

PMID- 21966106
TI  - Effect of Metformin on Hormonal and Biochemical Profile in PCOS Before and After
      Therapy.
AB  - Insulin resistance and the resultant hyperinsulinemia exacerbate the reproductive
      abnormalities of Polycystic Ovarian Syndrome by increasing ovarian androgen
      productions and decreasing serum sex hormone binding globulin. The present study
      was conducted to estimate serum insulin and testosterone level in 44 PCOS cases
      and 32 control patients. Simultaneously the role of metformin (an insulin
      sensitizing agent) in modulating insulin resistance and serum androgen level was
      also analyzed. A significant rise in serum insulin and testosterone (P < 0.001)
      was observed in cases in comparison to control. Fasting Plasma Glucose to insulin
      ratio, a marker of insulin resistance revealed a significant fall in PCOS group.
      Follow up of cases with metformin for 3 months revealed a significant fall in
      serum insulin (P < 0.05) with improvement in insulin resistance along with a
      nonsignificant fall in testosterone level. Serum insulin registered a significant
      positive correlation (P < 0.05) with serum testosterone revealing its etiological
      association. Thus administration of drugs ameliorating insulin levels is expected
      to provide new therapeutic modality for PCOS.

PMID- 21966107
TI  - Antioxidant effect of caffeic Acid on oxytetracycline induced lipid peroxidation
      in albino rats.
AB  - Caffeic acid is a well-known phenolic compound widely present in plant kingdom.
      The aim of this study was to investigate the possible protective effect of
      caffeic acid (CA) against oxytetracycline (OXT) induced hepatotoxicity in male
      Albino Wistar rats. A total of 30 rats weighing 150-170 g were randomly divided
      into five groups of six rats in each group. Oral administration of OXT (200 mg/kg
      body weight/day) for 15 days produced hepatic damage as manifested by a
      significant increase in serum hepatic markers namely aspartate transaminase
      (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate
      dehydrogenase (LDH), bilirubin and increased plasma and hepatic lipid
      peroxidation indices (TBARS and hydroperoxide). The present finding shows that
      the levels of enzymatic antioxidants namely superoxide dismutase (SOD), catalase
      (CAT) and glutathione peroxidase (GPx) were significantly decreased in OXT
      intoxicated rats. Upon oral administration of caffeic acid (40 mg/kg body
      weight/day) there were decreased hepatic marker activities, bilirubin and lipid
      peroxidation and increased enzymatic antioxidants in OXT + Caffeic acid group
      compared to Normal + OXT group(P < 0.05). Our study suggests that caffeic acid
      has antioxidant property and hepatoprotective ability against OXT induced
      toxicity.

PMID- 21966108
TI  - Turn Around Time (TAT) as a Benchmark of Laboratory Performance.
AB  - Laboratory analytical turnaround time is a reliable indicator of laboratory
      effectiveness. Our study aimed to evaluate laboratory analytical turnaround time
      in our laboratory and appraise the contribution of the different phases of
      analysis towards the same. The turn around time (TAT) for all the samples (both
      routine and emergency) for the outpatient and hospitalized patients were
      evaluated for one year. TAT was calculated from sample reception to report
      dispatch. The average TAT for the clinical biochemistry samples was 5.5 h for
      routine inpatient samples while the TAT for the outpatient samples was 24 h. The
      turnaround time for stat samples was 1 h. Pre- and Post-analytical phases were
      found to contribute approximately 75% to the total TAT. The TAT demonstrates the
      need for improvement in the pre- and post-analytical periods. We need to tread
      the middle path to perform optimally according to clinician expectations.

PMID- 21966109
TI  - Underestimation of impaired kidney function with serum creatinine.
AB  - Serum creatinine (SCr) levels are frequently used as a screening test to assess
      impaired renal function; however, patients can have significantly decreased
      glomerular filtration rate (GFR) with normal SCr values and making the
      recognition of kidney dysfunction more difficult. Hence, this study was designed
      to determine the extent of misclassification of the patients who have
      significantly reduced GFR as calculated by reexpressed four variable modification
      of diet in renal disease (MDRD) equation but, normal range of SCr. The study
      included 1040 in and out patients referred by physicians for serum creatinine
      measurement. When an exclusion criterion was applied 928 patients were qualified
      for the study. SCr was measured in 928 patients by a Roche kinetic compensated
      Jaffe's assay. GFR was calculated using reexpressed four variable MDRD study
      equation. Of the 928 patients 270 (29.1%) had renal dysfunction on the basis of
      eGFR (<60 ml/min/1.73 m(2)). However, with SCr only 162 (17.5%) patients had
      abnormal renal function (>1.5 mg/dl) and SCr values misrepresented (108) 11.6%
      patients with impaired kidney function. In addition, more females, about 15% were
      failed to detect by SCr method in contrast to males of 9%. This study documented
      that, a large proportion of patients with impaired renal function are not
      diagnosed if clinicians rely solely on normal SCr as evidence of normal renal
      function. Inclusion of eGFR calculated by re-expressed 4 variable MDRD equation
      may facilitates the early identification and intervention of patients with renal
      impairment.

PMID- 21966110
TI  - Parathyroid and calcium status in patients with thalassemia.
AB  - Thirty patients with thalassemia major receiving repeated blood transfusion were
      studied to see their serum parathyroid hormone (PTH) and calcium status. Serum
      PTH, serum and 24 h urinary calcium, and serum alkaline phosphatase, phosphorus,
      and albumin-corrected calcium levels were determined. Half of these patients, in
      addition to transfusion, were also supplemented with vitamin D (60,000 IU for
      10d) and calcium (1500 mg/day for 3 months). Serum PTH, and serum and 24 h
      urinary calcium concentrations of the patients receiving transfusions were found
      to be significantly reduced while their serum alkaline phosphatase, phosphorus,
      and albumin-corrected calcium levels were not significantly altered when compared
      to the respective mean values for the control group. Vitamin D and calcium
      supplementation significantly increased their serum PTH and calcium levels.
      Supplementations also increased urinary excretion of calcium. The results thus
      suggest that patients with thalassemia have hypoparathyroidism and reduced serum
      calcium concentrations that in turn were improved with vitamin D and calcium
      supplementation.

PMID- 21966111
TI  - Role of oxidative stress in various stages of psoriasis.
AB  - Psoriasis is a chronic inflammatory, proliferative skin disease characterized by
      pathological skin lesions due to various exogenous and endogenous factors. It is
      associated with a number of biochemical and immunological disturbances. Recently,
      it has been suggested that increased reactive oxygen species (ROS) production and
      compromised function of antioxidant system may be involved in the pathogenesis of
      this disease. In the present study, 90 psoriasis patients were selected. Disease
      severity was assessed by psoriasis area severity index score and grouped as mild,
      moderate and severe (each group consists of 30 subjects) and compared with 30
      healthy controls. Serum levels of malondialdehyde, nitric oxide end products and
      the activities of antioxidant enzymes such as erythrocyte-superoxide dismutase,
      catalase and total antioxidant status were investigated in these groups/subjects.
      As compared to controls, we found severitywise significantly increased serum
      malondialdehyde, nitric oxide end products with decrease in erythrocyte
      superoxide dismutase activity, catalase activity and total antioxidant status in
      patients with psoriasis suggesting worsening of the disease. It seems to be
      linked with the enhancement of Reactive Oxygen Species production and decreased
      antioxidant potential in psoriasis.

PMID- 21966113
TI  - Age-dependent changes in glutathione-s-transferase: correlation with total plasma
      antioxidant potential and red cell intracellular glutathione.
AB  - The correlation between antioxidant capacity and oxidative damage during aging
      has been reported in several tissues in different species. Glutathione-S
      transferases (GST) can metabolise endogenous and exogenous toxins and carcinogens
      by catalysing the conjugation of diverse electrophiles with reduced glutathione
      (GSH). We observe a significant (P < 0.001) increase in plasma GST activity as a
      function of human age (r = 0.5675). A significant (P < 0.001) positive
      correlation (r = 0.8979) is observed between GST activity and total plasma
      antioxidant potential measured as ferric reducing ability of the plasma (FRAP).
      GST activity and red cell intracellular GSH also show a significant positive
      correlation (r = 0.7014). We hypothesize that the increased activity of plasma
      GST is a manifestation of increased generation of ROS and a concomitant decrease
      in the level of plasma antioxidant capacity during aging.

PMID- 21966112
TI  - Effect of turmeric and its active principle curcumin on t(3)-induced oxidative
      stress and hyperplasia in rat kidney: a comparison.
AB  - The present study was designed to compare the potential of turmeric and its
      active principle curcumin on T(3)-induced oxidative stress and hyperplasia. Adult
      male Wistar strain rats were rendered hyperthyroid by T(3) treatment (10 MUg .
      100 g(-1) . day(-1) intraperitoneal for 15 days in 0.1 mM NaOH) to induce renal
      hyperplasia. Another two groups were treated similarly with T(3) along with
      either turmeric or curcumin (30 mg kg(-1) body weight day(-1) orally for 15
      days). The results indicate that T(3) induces both hypertrophy and hyperplasia in
      rat kidney as evidenced by increase in cell number per unit area, increased
      protein content, tubular dilation and interstitial edema. These changes were
      accompanied by increased mitochondrial lipid peroxidation and superoxide
      dismutase activity without any change in catalase activity and glutathione
      content suggesting an oxidative predominance. Both turmeric and curcumin were
      able to restore the level of mitochondrial lipid peroxidation and superoxide
      dismutase activity in the present dose schedule. T(3)-induced histo-pathological
      changes were restored with turmeric treatment whereas curcumin administration
      caused hypoplasia. This may be due to lower concentration of curcumin in the
      whole turmeric. Thus it is hypothesized that regulation of cell cycle in rat
      kidney by T(3) is via reactive oxygen species and curcumin reveres the changes by
      scavenging them. Although the response trends are comparable for both turmeric
      and curcumin, the magnitude of alteration is more in the later. Turmeric in the
      current dose schedule is a safer bet than curcumin in normalizing the T(3)
      induced hyperplasia may be due to the lower concentration of the active principle
      in the whole spice.

PMID- 21966114
TI  - Potential Effect of Bacopa monnieri on Nitrobenzene Induced Liver Damage in Rats.
AB  - The study was designed to evaluate the hepatoprotective activity of ethanolic
      extract of Bacopa monnieri in acute experimental liver injury induced by
      Nitrobenzene in rats. The extract at the dose of 200 mg/kg body weight was
      administered orally once every day for 10 days. The increased serum marker
      enzymes, Aspartate transaminase, Alanine transaminase and alkaline phosphatase
      were restored towards normalization significantly by the extract. Significant
      increase in SOD, CAT and GPx was observed in extract treated liver injured
      experimental rats. Histopathological examination of the liver tissues supported
      the hepatoprotection. It is concluded that the ethanolic extract of Bacopa
      monieri plant possess good hepatoprotective activity.

PMID- 21966115
TI  - Hypolipidemic Effect of Celastrus paniculatus in Experimentally Induced
      Hypercholesterolemic Wistar Rats.
AB  - The objective of the present study was to evaluate hypolipidemic effect of
      methanolic extract of Celastrus paniculatus in experimentally induced
      hypercholesterolemic rats. Hypercholesterolemia was induced by feeding the
      animals with high fat diet. Oral administration of methanolic seed extract (50%)
      of Celastrus paniculatus at the optimized dose of 65 mg/kg body weight,
      substantially reduced the plasma total cholesterol, triglycerides and LDL
      cholesterol in comparison with induced hypercholesterolemic animal group and the
      results were comparable with the standard hypocholesterolemic drug and almost
      similar to the control group. Atherogenic index and liver weight of treated
      animals also showed significant decrease compared to the hypercholesterolemic
      animals. It substantially increased the HDL cholesterol level as compared to
      control group. A significant increase in the activities of lipoprotein lipase and
      plasma LCAT enhanced hepatic bile acid synthesis and thereby, increased
      degradation of cholesterol to neutral sterols. Furthermore, the activities of HMG
      CoA reductase, glucose 6-phosphate dehydrogenase and malate dehydrogenase were
      significantly reduced. Histological studies showed less cholesterol deposits in
      the aorta of animals fed with seed extract of C. paniculatus compared to the
      induced hypercholesterolemic animals not given C. paniculatus supplement.

PMID- 21966116
TI  - Evaluation of oxidative stress and antioxidant status in pregnant anemic women.
AB  - The present study was conducted to investigate the oxidant-antioxidant status in
      iron deficient pregnant anemic women. One hundred thirty pregnant women with iron
      deficiency anemia (IDA) were divided into three groups, namely mild (50),
      moderate (50) and severe (30) anemic along with pregnant healthy women as
      controls (50). The complete blood count, plasma lipid peroxidation products,
      enzymatic and non-enzymatic antioxidants were measured according to respective
      protocols. The levels of complete blood count, iron, ferritin along with
      antioxidant enzymes namely catalase, superoxide dismutase, glutathione
      peroxidase, glutathione reductase and reduced glutathione were significantly
      reduced in all IDA groups. However, the level of oxidized glutathione, lipid
      peroxides, protein carbonyls, conjugated dienes were found significantly
      increased in all anemic patients. Antioxidant vitamins, namely C, E and A were
      also found significantly decreased in IDA patients. On the basis of our results,
      it may be concluded that IDA tends to increase the pro-oxidant components, which
      may result in various complications including peroxidation of vital body
      molecules resulting in increased risk for pregnant women as well as fetus.

PMID- 21966117
TI  - Protective Effect of Emblica officinalis Against Alcohol-Induced Hepatic Injury
      by Ameliorating Oxidative Stress in Rats.
AB  - The effect of Emblica officinalis fruit extract (EFE) against alcohol-induced
      hepatic damage in rats was investigated in the present study. In vitro studies
      showed that EFE possesses antioxidant as well nitric oxide (NO) scavenging
      activity. In vivo administration of alcohol (5 g/kg b.wt/day) for 60 days
      resulted increased liver lipid peroxidation, protein carbonyls, nitrite plus
      nitrate levels. Alcohol administration also significantly lowers the activities
      of superoxide dismutase, catalase, glutathione peroxidase, glutathione S
      transferase and reduced glutathione as compared with control rats. Administration
      of EFE (250 mg/kg body weight) to alcoholic rats significantly brought the plasma
      enzymes towards near normal level and also significantly reduced the levels of
      lipid peroxidation, protein carbonyls and restored the enzymic and non-enzymatic
      antioxidants level. This observation was supplemented by histopathological
      examination in liver. Our data indicate that the tannoid, flavonoid and NO
      scavenging compounds present in EFE may offer protection against free radical
      mediated oxidative stress in rat hepatocytes of animals with alcohol-induced
      liver injury.

PMID- 21966118
TI  - Evaluation of Flow Rate, pH, Buffering Capacity, Calcium, Total Proteins and
      Total Antioxidant Capacity Levels of Saliva in Caries Free and Caries Active
      Children: An In Vivo Study.
AB  - The purpose of this study was to evaluate the relationship between the
      physicochemical properties of saliva such as flow rate, pH, buffering capacity,
      calcium level, total protein and total antioxidant levels in caries free and
      caries active children. The present study included one hundred and twenty healthy
      children who were divided into two groups; group I and group II comprising of age
      groups 7-10 and 11-14 years, respectively. Both the groups were then sub-divided
      equally according to gender. They were further divided into caries free and
      caries active with 15 children in each group. Unstimulated saliva was collected
      by suction method and flow rates were determined. The samples were then analyzed
      for pH, buffering capacity, total protein, calcium and total antioxidant
      capacity. The data was statistically analyzed using student t test (unpaired).
      The results revealed that when all these parameters were compared among the
      caries free and caries active children, flow rate, pH, buffering capacity were
      slightly reduced in caries active children, but total protein and total
      antioxidant capacity of saliva increased significantly in caries active children
      and the total calcium decreased significantly in caries active children. Within
      the limitation of this study, we conclude that, the physicochemical properties of
      saliva play a major role in the development of caries.

PMID- 21966119
TI  - Anti-Oxidative Effect of Cassia auriculata on Streptozotocin Induced Diabetic
      Rats.
AB  - The anti oxidative effect of administration of 100 mg/kg bw and 200 mg/kg bw of
      the flower powder of Cassia auriculata (CFP) for 45 days to normoglycemic and
      diabetic rats (streptozotocin induced) was studied. Anti oxidative effect was not
      observed in normoglycemic rats in the experiment. There was significant (P >
      0.05) increase in the level of Thio Barbituric Acid Reactive Substances (TBARS),
      hydroperoxide and conjugated dienes and significant (P > 0.05) decrease in the
      catalase, superoxide dismutase and glutathione peroxidase activities and in the
      level of ascorbic acid, vitamin E and reduced glutathione in diabetic rats. The
      flower powder of Cassia auriculata significantly (P > 0.05) decreased the TBARS,
      hydroperoxide and conjugated dienes and increased the antioxidant enzymes
      (catalase, superoxide dismutase and glutathione peroxidase) and non enzymic anti
      oxidants (ascorbic acid, vitamin E and reduced glutathione). The antioxidatve
      effect of 200 mg/kg bw CFP was significantly (P > 0.05) better than 100 mg/kg bw
      CFP and the reference drugs (tolbutamide and metformin). The mode of action of
      CFP remains to be elicited.

PMID- 21966120
TI  - The Diagnosis of alpha-Thalassaemia: A Case of Hemoglobin H -alpha Deletion.
AB  - We report a case of hemolytic anemia that was subsequently identified to be a
      case of alpha-thalassaemia harboring the common rightward 3.7 kb deletion/HbH.
      The diagnosis was based on sequential analyses using BioRad D10 HPLC, Alkaline
      gel electrophoresis, GPO alpha THAL-IC strips and the identification of the
      specific genetic lesion using an alpha Globin reverse dot blot hybridization
      assay. Supravital stain of RBCs helped in identifying classical HbH inclusions.
      In a background of a variable clinical presentation, lack of definitive
      hematological markers, and general under-diagnosis of alpha-thalassaemias we have
      used this case to highlight the features and sequence of techniques involved in
      identifying and characterizing an alpha-globin chain mutation, starting from a
      diffuse clinical history and presentation up to the identification of a specific
      genetic lesion involved.

PMID- 21966121
TI  - To study the effect of diet supplementation with coconut oil, mustard oil and
      sunflower oil on blood lipids in rabbit.

PMID- 21966122
TI  - Efficiency of diagnostic methods for correlation between prevalence of enteric
      protozoan parasites and HIV/AIDS status--an experience of a tertiary care
      hospital in East Delhi.
AB  - Since the beginning of the AIDS pandemic, opportunistic infections have been
      recognized as common complications of HIV infection. Enteric protozoan parasitic
      infections are one of the leading causes of morbidity and mortality in HIV
      infected patients. The present study is, therefore, aimed to determine the
      prevalence of these parasites and study their association with immune status in
      HIV patients with emphasis on the correlation between various diagnostic
      techniques to give an accurate diagnosis to avoid empirical treatment. This
      prospective study, carried out between November 2009 and May 2010 included all
      HIV seropositive patients presenting with diarrhea to the ART center. A total of
      64 stool samples were analyzed by wet mount examination, three different staining
      techniques, and antigen detection by ELISA for various enteric protozoan
      infections. Total prevalence of enteric protozoan parasites was 30%. Among the
      total cases, Cryptosporidium was seen in 12% cases followed by Giardia, E.
      histolytica and Isospora belli. The maximum diagnostic yield for coccidian
      parasites was with safranin-methylene blue staining technique. Parasitic burden
      contributes towards early morbidity in HIV infection. This study provides
      important information about prevalence of intestinal protozoan parasites in HIV
      infection. A combination of procedures should be carried out for the screening of
      stool specimens of HIV patients for better diagnosis and management.

PMID- 21966124
TI  - Mosquito larvicidal potential of potash alum against malaria vector Anopheles
      stephensi (Liston).
AB  - Mosquito larviciding may prove to be an effective tool for incorporating into
      integrated vector management strategies for reducing malaria transmission. Here,
      we report the potential of potash alum, a traditionally known salt in Indian
      Ayurveda and Chinese medicine system, in malaria vector control by evaluating its
      aqueous suspension as larvicide and growth disruptor of Anopheles stephensi,
      under laboratory conditions. Immature stages of the mosquito were tested using
      WHO guidelines. 50 and 90% lethal concentrations among various larvae ranged
      between 2.1 to 48.74 ppm and 15.78 to 93.11 ppm, respectively. The results
      indicated that larvicidal effects of potash alum were comparable to various
      biological and chemical insecticides. The study provides considerable scope in
      exploiting local indigenous resources for the control of nuisance mosquito
      vectors.

PMID- 21966123
TI  - Antibody responses to 43 and 48 kDa antigens of blood-stage Plasmodium berghei in
      Balb/c mice.
AB  - Progress towards a vaccine against malaria is advancing rapidly with several
      candidate antigens being tested for their safety and efficacy. In present
      investigation, two polypeptides (43 and 48 kDa) of Plasmodium berghei (NK-65)
      were identified by sodium dodecyl sulfate polyacrylamide gel electrophoresis.
      Immunogenicity and protective efficacy of both these polypeptides formulated in
      saponin has been compared in Balb/c mice against challenge infection with P.
      berghei. Antibody responses were evaluated by indirect fluorescent antibody test
      and enzyme-linked immunosorbent assay. Merozoite invasion inhibition assay and
      challenge infections revealed that 48 kDa antigen is better immunogen as compared
      to 43 kDa and provide better protection against rodent malaria infection.

PMID- 21966125
TI  - Helminth parasite communities in anuran amphibians of Kalesar Wildlife Sanctuary
      (Haryana), India.
AB  - Helminth parasite fauna in anuran amphibia were investigated during the general
      faunistic surveys of Kalesar Wildlife Sanctuary, situated in Haryana state. Three
      species of amphibian hosts were found to harbour 12 genera of helminth parasites.
      The prevalence, intensity and abundance were studied. Euphlyctis cyanophlyctis
      harboured maximum parasite species followed by Fejervarya limnocharis and
      Duttaphrynus melanostictus. In E. cyanophlyctis, among nematode parasites, the
      genus Camallanus was most prevalent followed by Cosmocerca and Cosmocercoides,
      whereas, Rhabdias and Aplectana were the least prevalent genera. Among trematode
      parasites, Ganeo was the most prevalent genus and least was Diplodiscus.
      Acanthocephalus was recovered only once and no cestode infection was found. In F.
      limnocharis, the most prevalent nematode genus was Oxysomatium, followed by
      Cosmocerca and the only trematode recorded was Ganeo, whereas, cestode
      Proteocephalus was also recovered once. In D. melanostictus, only two nematode
      genera were recovered of which Oxysomatium was dominant followed by Cosmocerca.
      The helminth parasite community in anuran amphibia of Kalesar WLS comprised 52.9%
      of nematodes, 46.2% of trematodes, 0.58% cestodes and 0.29% acanthocephala.

PMID- 21966126
TI  - Potentilla fulgens (Family Rosaceae), a medicinal plant of north-east India: a
      natural anthelmintic?
AB  - The cestode parasite, Raillietina echinobothrida and the trematode, Gastrothylax
      crumenifer were exposed to the ethanolic root peel extract of Potentilla fulgens,
      an antiparasitic local medicinal plant of Meghalaya, India, to evaluate the
      anthelmintic efficacy of the plant. The parasites were incubated in 1, 5, 10, 20,
      50 and 100 mg crude alcoholic extract per ml of phosphate buffered saline (PBS)
      at a temperature of 37 +/- 1 degrees C. Paralysis and death were observed at 2.00
      +/- 0.05 and 2.80 +/- 0.06 h for the cestode and 1.21 +/- 0.06 and 2.18 +/- 0.04
      h for the trematode parasites at the highest test concentration of the plant
      extract. The commercial anthelmintic, Praziquantel (PZQ) showed higher activity
      at the tested concentration (0.02 mg/ml). To further investigate the efficacy of
      the plant extract, vital tegumental enzymes of the parasite viz. Acid phosphatase
      (AcPase), Alkaline phosphatase (AlkPase) and Adenosine triphosphatase (ATPase)
      were studied. Quantitatively, the total enzyme activity of AcPase, AlkPase and
      ATPase was found to be reduced significantly by 69.20, 66.43 and 29.63% for R.
      echinobothrida and 47.96, 51.79 and 42.63% for G. crumenifer, respectively
      compared to the respective controls; histochemical study also showed reduction in
      the visible staining of the enzymes. The reference drug, PZQ also showed more or
      less similar effect like that of the plant extract. The result suggests that
      phytochemicals of P. fulgens have anthelmintic potential.

PMID- 21966127
TI  - On a new species of Neoechinorhynchus Hamann, 1892 (Acanthocephala:
      Neoechinorhynchoidea Southwell et Macfie, 1925) from Indian threadfin fish,
      Leptomelanosoma indicum Shaw, 1804 from Visakhapatnam coast, Andhra Pradesh,
      India.
AB  - A new acanthocephalan of the genus Neoechinorhynchus Hamman, 1892
      (Acanthocephala: Neoaechinorhynchoidea Southwell et Macfie, 1925) parasitic on
      threadfin fish, Leptomelanosoma indicum Shaw, 1804 from Visakhapatnam coast,
      Andhra Pradesh, India is described. Neoechinorhynchus indicus sp. nov is
      characterized by an enormous body size, structural characteristics of the hooks
      on proboscis, presence of body annulations, two guard cells, unequal lemnisci,
      sub-terminal genital pore and the host. N. indicus sp.nov is included in the
      genus by the presence of three rows of six hooks each on the proboscis and a
      single layered proboscis receptacle.

PMID- 21966128
TI  - Dracunculiasis in tribal region of southern Rajasthan, India: a case report.
AB  - Although the Rajasthan state was declared rid off from dracunculiasis in 1997,
      nevertheless two cases in succession 2002 and 2003 were reported and the present
      is third one which is being reported from Dungarpur district of Rajasthan, India.

PMID- 21966129
TI  - Infestation of isopod parasites in commercial marine fishes.

PMID- 21966130
TI  - A short note on heavy infection of acanthocephalan worm (Neoechinorhynchus
      agilis) in grey mullet, Mugil cephalus.
AB  - Infection with acanthocephalan parasite, Neoechinorhynchus agilis
      (Acanthocephala: Neoechinorhynchidae) is reported from adult mullet (Mugil
      cephalus). Heavy infections with the parasites were observed in the posterior
      region of the intestine, almost blocking the lumen. At the site of parasite
      attachment, the surface of the intestine appeared thickened and the mucosal
      epithelium. A description of the parasites and its clinicopathology is discussed.

PMID- 21966131
TI  - Surgery in safe hands.

PMID- 21966132
TI  - Principles of physics in surgery: the laws of mechanics and vectors physics for
      surgeons-part 2.
AB  - In this sequel, to an earlier article, we discuss the laws of Mechanics,
      Thermodynamics and Vectors as they apply to soft and bony tissues. These include
      the Laplace's Law as applied to colonic perforation, compression therapy,
      parturition, variceal rupture, disc herniations etc. The Pascal's Law finds use
      in hernia repair and the Heimlich maneuver. Trigonometrically derived components
      of forces, acting after suturing, show ways to reduce cut-through; the thickness
      and the bite of suture determines the extent of tissue reaction. The heating
      effect of current explains the optimum gap between the prongs of a bipolar
      cautery and the use of law of transfer of heat in determining relation between
      healthy wound healing and ambient temperature.

PMID- 21966133
TI  - Phrenic-recurrent nerve anastomosis in animal models with unilateral cutting of
      the recurrent nerve.
AB  - In our experimental study, the aim was to recover vocal cord physiology in
      cutting of recurrent laryngeal nerve, thus phrenic-recurrent nerve transposition
      was planned in rabbits. Experiments were performed on 10 experimental and 10
      control rabbits. The right recurrent nerve was cut in the control group, while in
      the experiment group, the right recurrent nerve was cut. Then, a right phrenic
      recurrent nerve end-to-end anastomosis was performed and the results were
      evaluated. After the 3rd postoperative week, videolaryngoscopy (VLS) and
      intramuscular electromyography (EMG) could not be evaluated in 1 rabbit from the
      experimental group which had died during anesthesia. In eight of the nine rabbits
      in the experiment which underwent VLS and EMG, activity was recorded in the right
      vocal cords. On light microscopic examination, atrophy was not detected in the
      vocal cord muscles of 9 rabbits among the 10 in the experiment group, while all
      rabbits in the control group and 1 rabbit in the experiment group were diagnosed
      with vocal cord atrophy. A success rate of approximately 90% was obtained based
      on the pathologic examination. We believe that the method can be used in patients
      without any contraindications, considering the complications of tracheostomy and
      the quality of life.

PMID- 21966134
TI  - Closure of the Common Duct -Endonasobiliary Drainage Tubes vs. T Tube: A
      Comparative Study.
AB  - For the last century T tube drainage of the bile duct has remained standard
      practice following choledochlithotomy. It vents the biliary tree, provides route
      for cholangiography and management of residual stones. However, T tubes are
      associated with significant complications. This retrospective study compared the
      use of Endonasobiliary drainage tubes and the T tube in 66 patients who underwent
      open choledocholithotomy for effectiveness and complications. Both groups were
      statistically comparable. Only 15.15% patients in the Endonasobiliary drainage
      group, while 45.45% patients in the T tube group developed complications. Severe
      complications such as biliary peritonitis and intraperitoneal collections were
      noted only in the T tube group. The Endonasobiliary drainage tube was removed
      significantly earlier and patients from this group were discharged earlier as
      compared to those in the T tube. The Endonasobiliary drainage tube is as
      effective as the T tube in postoperative biliary drainage and allows
      cholangiograms to be performed. Its use is associated with less complications and
      it can be removed safely earlier than the T tube. Thus patients have a shorter
      time with tubes and can be discharged home earlier.

PMID- 21966135
TI  - Is fourth port really required in laparoscopic cholecystectomy?
AB  - Since the advent of four-port laparoscopic cholecystectomy, many modifications
      regarding port number and size have been tried. The feasibility of three-port
      technique has been found comparable to the conventional four-port laparoscopic
      cholecystectomy. To assess the feasibility and safety of three-port laparoscopic
      cholecystectomy in a prospective study. Between March 2007 and March 2009, fifty
      patients with cholelithiasis aged between 15 and 56 years underwent three-port
      cholecystectomy in a prospective study in Government medical college, Srinagar. A
      single surgeon did all the cases and there was no criterion for the patient
      selection. These were consecutive fifty surgeries done by the surgeon. The
      outcome was assessed in terms of intra-operative and post-operative parameters.
      The mean (range) age was 45 (15-56) years and there were thirty-nine females and
      eleven males in the study. All the procedures were completed successfully without
      any conversions to open or any major complications; though three patients needed
      the addition of a fourth port as in conventional laparoscopic cholecystectomy.
      The mean (range) operative time was 55 (30-90) min and the average blood loss was
      30 ml. The mean (range) hospital stay was 1 (1-3) days. All patients returned to
      routine work within 1 week of surgery. The mean follow-up was 5 (2-7) months. We
      conclude, from the results above, that three-port laparoscopic cholecystectomy is
      safe and feasible. There are only two visible surgical scars, better cosmetic
      appearance with no increased risk of bile duct injury. It reduces the manpower in
      the form of a second assistant. Thus, it can be recommended as a safe alternative
      procedure to conventional four-port laparoscopic cholecystectomy.

PMID- 21966136
TI  - Combined procedures with laparoscopic cholecystectomy.
AB  - With advancement in laparoscopic surgery a number of surgical procedures can be
      performed combined with laparoscopic cholecystectomy in a single surgery. We
      evaluate the safety & efficacy of such surgeries. A retrospective review of all
      patients who had undergone combined procedures with laparoscopic cholecystectomy
      during January 2005 to June 2009 was performed. 3144 laparoscopic
      cholecystectomies were performed in the period from January 2005 to June 2009. Of
      these, 401 cases were combined with another procedure. The mean operative time
      was 80 min (range 50-270 min). The mean hospital stay was 3.2 days (range 1-5
      days). The mean no. of days injectable analgesics was required was 2 days (range
      1 day-4 days). Combined procedures provide patients with all the benefits of
      minimal invasive surgery and also give the benefit of single time anaesthesia
      without adding to post operative morbidity & hospital stay.

PMID- 21966137
TI  - Pancreaticoduodenectomy in a government medical college-should we proceed!!!
AB  - The value of standard Pancreaticoduodenectomy for Periampullary carcinomas has
      long been a matter of debate. Though the mortality has dramatically reduced in
      high volume centers with dedicated hepatobiliary surgery units, the rate is still
      high in peripheral institutes. In this study our aim was to access the overall
      post operative outcome associated with pancreaticoduodenectomy performed in a
      government medical college. A total of 44 patients who underwent
      pancreaticoduodenectomy for operable periampullary cancers were evaluated. The
      overall morbidity rate was 31.1%. A total of 13 (29.5%) died following the
      operation and of its complications though the rate has reduced drastically to
      14.2% in2008. The average length of hospital stay was 22 days. The mean survival
      was 15 months. Pancreaticoduodenectomy can safely be performed in government
      medical colleges with good results. In view of the majority of the patients in
      rural and suburban communities, not all patients need referral to higher centers.

PMID- 21966138
TI  - An In Vitro and In Vivo Evaluation of Tensile Strength and Durability of Seven
      Suture Materials in Various pH and Different Conditions: An Experimental Study in
      Rats.
AB  - Development in material engineering provide many kinds of suture materials to
      medical fields. The choice of utilization depends on the surgeons decision, the
      durability, absorbtion times, tensile strength of the suture, and operation site
      in means of organ and tissue. In this study we aimed to investigate 7 different
      suture materials in vivo and in vitro conditions to evaluate the properties and
      durability. Basal tensile strength (TS) values of all sutures were measured and
      168 Wistar albino rats were utilised in vivo groups. The sutures were placed in
      the bladder, stomach, intestine and bile duct (after obstructive jaundice). Urine
      and bile of rat, pH 1 and pH 10 were used as in vitro conditions. Seven different
      suture materials (Maxon, Vicryl, Plain Catgut, Surgical Silk, Polypropylene,
      Caprosyn and Biosyn) were investigated in 9 different in vitro and in vivo
      conditions. All sutures were chosen to be in size 5/0. In the following 5th day
      the sutures were tested related to durability and stability. Results were
      compared stastically using the Mann-Whitney U test and p < 0.05 was considered as
      stastically significant. Among all the suture materials only polypropylene proved
      to preserve its stability in vivo and in vitro surveys. Cat-gut and caprosyn lost
      its TS in all medias. Silk and biosyn lost its TS in all conditions except the
      stomach and intestines. Maxon also lost its TS in all condition except urine.
      Utilisation of caprosyn and biosyn in urinary procedures reduces stone formation
      and infections. The suture of choice in biliary tract should be vicryl, maxon or
      biosyn since polypropylene preserves its stability that could result in stone
      formation. In intestinal operations polypropylene, vicryl, and silk could be
      preferred.

PMID- 21966139
TI  - Laparoscopic cholecystectomy in situs inversus-our experience of 6 cases.
AB  - Laparoscopic cholecystectomy is the standard procedure for symptomatic gall stone
      disease. Situs inversus is a condition where the visceral anatomy is reversed.
      Laparoscopic cholecystectomy in a patient of situs inversus is a technically
      difficult procedure. Six patients of situs inversus underwent laparoscopic
      cholecystectomy from January 2003 to December 2009. In the first patient of situs
      inversus, we operated by placing the ports in mirror image fashion as that of
      standard laparoscopic cholecystectomy. However in next five patients we modified
      the technique by interchanging the epigastric and left mid clavicular line ports
      to overcome the problem of handedness. The procedure was successfully completed
      in all six patients. No intraoperative or postoperative complications occurred.
      The mean operating time was 65 mins (45-85 mins). Laparoscopic cholecystectomy is
      safe in patients of situs inversus. However, extreme care and skill is required
      to identify the reversed anatomy and to overcome the problem of handedness.
      Interchanging the epigastric and left mid clavicular line ports makes the
      procedure easier.

PMID- 21966140
TI  - Laparoscopic CBD Exploration.
AB  - Laparoscopic CBD exploration (LCBDE) is a cost effective, efficient and minimally
      invasive method of treating choledocholithiasis. Laparoscopic Surgery for common
      bile duct stones (CBDS) was first described in 1991, Petelin (Surg Endosc 17:1705
      1715, 2003). The surgical technique has evolved since then and several studies
      have concluded that Laparoscopic common bile duct exploration(LCBDE) procedures
      are superior to sequential endolaparoscopic treatment in terms of both clinical
      and economical outcomes, Cuschieri et al. (Surg Endosc 13:952-957, 1999), Rhodes
      et al. (Lancet 351:159-161, 1998). We started doing LCBDE in 1998.Our experience
      with LCBDE from 1998 to 2004 has been published, Gupta and Bhartia (Indian J Surg
      67:94-99, 2005). Here we present our series from January 2005 to March 2009. In a
      retrospective study from January 2005 to March 2009, we performed 3060
      laparoscopic cholecystectomies, out of which 342 patients underwent
      intraoperative cholangiogram and 158 patients eventually had CBD exploration. 6
      patients were converted to open due to presence of multiple stones and 2 patients
      were converted because of difficulty in defining Calots triangle; 42 patients
      underwent transcystic clearance, 106 patients had choledochotomy, 20 patients had
      primary closure of CBD whereas in 86 patients CBD was closed over T-tube; 2
      patients had incomplete stone clearance and underwent postoperative ERCP.
      Choledochoduodenosotomy was done in 2 patients. Patients were followed regularly
      at six monthly intervals with a range of six months to three years of follow-up.
      There were no major complications like bile leak or pancreatitis. 8 patients had
      port-site minor infection which settled with conservative treatment. There were
      no cases of retained stones or intraabdominal infection. The mean length of
      hospital stay was 3 days (range 2-8 days). LCBDE remains an efficient, safe, cost
      effective method of treating CBDS. Primary closure of choledochotomy in select
      patients is a viable & safe option with shorter operative time and length of
      stay. LCBDE can be performed successfully with minimal morbidity & mortality.

PMID- 21966141
TI  - Hybrid Single-incision Laparoscopic Restorative Proctocolectomy with Ileal Pouch
      Anal Anastomosis for Ulcerative Colitis.
AB  - Single-incision laparoscopic surgery is a rapidly evolving field as a bridge
      between traditional laparoscopic surgery and natural orifice transluminal
      endoscopic surgery. We report one of the initial clinical experiences from India
      for Laparoscopic Restorative Proctocolectomy and Ileal Pouch Anal Anastomosis
      (RPC IPAA) with this new technique. A SILSTM port was used through the curved
      intra-umbilical 25-mm incision. A 12-mm port was placed in the right iliac fossa
      at the ileostomy site. Another 5 mm port was placed in the left iliac fossa at
      the drain site. 10 mm 0 degree lens was used through the SILS port. Two 5 mm port
      were placed from the SILS port. Right iliac fossa port was the surgeon's right
      hand port and left hand port was 5 mm SILS port. Left iliac fossa port and 5 mm
      SILS port were used by the assistant surgeon for retraction. The specimen was
      delivered through the umbilical incision by extending the incision for 1.5 cm on
      either side. Ileal J Pouch was created extracorporeally and then anastomosed to
      the anal canal with the circular stapler laparoscopically. The diverting loop
      ileostomy was brought out through the right iliac fossa 12 mm port. The pelvic
      drain was brought out through the left iliac fossa port. The procedure was
      completed without any perioperative complications. Operative time was 256
      minutes. Postoperative follow-up did not reveal any umbilical wound complication.
      Till date we have performed 26 Laparoscopic RPC with IPAA and this was the first
      Single Incision Laparoscopic RPC with IPAA. For experienced laparoscopic
      colorectal surgeons, single incision laparoscopic colectomy (SILC) is feasible.
      Single-incision laparoscopic colectomy is a promising alternative method as
      minimally invasive abdominal surgery for the treatment of patients requiring
      colectomy.

PMID- 21966142
TI  - Ruptured heterotopic pregnancy: a rare cause for hemoperitoneum; report of three
      cases from kashmir, India.
AB  - Heterotopic pregnancy has been found in various forms but is still a rare event
      in the natural conception cycles, occurring in less than 1:30000 pregnancies with
      the incidence rising to 1:100 to 1:500 pregnancies duo to assisted reproductive
      technologies. Delay in diagnosing the condition can be fatal for both the mother
      and the fetus. Three patients aged 28, 31 and 26 years presented with amenorrhea
      of ten, eight and twelve weeks duration respectively with signs of peritonism and
      shock. Investigations revealed intra and extra uterine pregnancies in all the
      three cases with the rupture of the extra uterine pregnancies. All the cases were
      operated and first two cases were followed up postoperatively till the delivery
      of the term live babies. The third case is still under our follow up. A high
      index of suspicion by a general surgeon is needed in arriving at a prompt
      diagnosis of ruptured heterotopic pregnancy so that rapid resuscitation, heart
      sparing anesthesia and expeditious surgery is carried out for both maternal and
      intrauterine fetal wellbeing.

PMID- 21966143
TI  - Spontaneous common bile duct perforation presenting as acute abdomen.
AB  - Spontaneous common bile duct (CBD) perforation is an unusual cause of acute
      abdomen. It is rarely suspected or correctly diagnosed preoperatively. Clinical
      presentation is as biliary peritonitis. The common causes are CBD calculus
      disease, tumors of the bile duct, choledochal cyst and sometimes idiopathic.
      Treatment is surgical and consists of CBD exploration and repair over a T tube.

PMID- 21966144
TI  - A rare case of desmoid tumor of thigh.
AB  - Extraabdominal desmoid tumor is a locally aggressive tumor despite being
      histologically benign. To avoid local recurrence, it is important to
      preoperatively detect the exact localization and extension of the infiltrating or
      disseminating lesion in this tumor. We report a case of recurrent extraabdominal
      desmoid tumor, which arose in the posterior thigh region. A 68 yrs old male
      presented with thigh swelling since past 22 years over posterior aspect of thigh
      increasing in size over the past 2years. The swelling was extending over the
      medial and anterior aspect of thigh. On investigation he was found to be case of
      desmoid tumor of thigh.

PMID- 21966145
TI  - Isolated gastric tuberculosis: a case report and review of literature.
AB  - Isolated gastric tuberculosis is a rare condition, even in those parts of the
      world where intestinal tuberculosis is common. Herein we describe a case of a
      thirty year old female patient with isolated gastric tuberculosis who presented
      with features of gastric outlet obstruction.

PMID- 21966146
TI  - Enormous disfiguring thyroid swelling.
AB  - A 35 year old woman presented to us with a huge thyroid swelling (17 * 11 * 14
      cm) in front of her neck which she had for the last 10 years. She was not toxic
      or dyspnoeic. It was multinodular with areas of firmness and cystic feeling. She
      had some degree of tracheal compression but no intra thoracic extension as
      confirmed by a CT scan of the neck. Endotracheal intubaton was done and she was
      operated on using a long transverse incision with division of the strap muscles
      for better exposure. She did not need a tracheostomy and the post operative
      period was uneventful. The histopathological revealed a goitre.

PMID- 21966147
TI  - Roundworm in a chest drain.
AB  - A 19 year old man who suffered a stab injury in the epigastric region and had a
      chest drain was referred to our accident and emergency department. A chest x-ray
      showed left sided opacities with fundic gas in the region of the left
      hemithorax.A roundworm was seen in the chest tube. An exploratory laparotomy
      revealed a diaphragmatic tear with a laceration of the anterior wall of the
      stomach from which multiple roundworms were coming out and had entered the
      pleural cavity and then the chest drain. The tears were repaired and abdomen
      closed. The patient is doing well.

PMID- 21966148
TI  - Unilocular cystic lymphangioma of thigh-an extremely rare clinical entity.
AB  - Majority of cystic lymphangiomas are multilocular and occur in neck and axilla.
      The cystic lymphangioma is also known as cystic hygroma. Unilocular cystic
      hygroma of neck and breast have been reported in literature and have been termed
      hydrocele of neck and breast respectively. However unilocular cystic hygroma of
      thigh is probably being reported for the first time.

PMID- 21966149
TI  - Chronic Groin Pain Following Lichtenstein Mesh Hernioplasty for Inguinal Hernia.
      Is It a Myth, How True is It?

PMID- 21966150
TI  - Biotechnology in the realm of history.

PMID- 21966151
TI  - Patterns of glycemic control using glycosylated hemoglobin in diabetics.
AB  - AIM: Till now estimation of blood glucose is the highly effective method for
      diagnosing diabetes mellitus but it provides a short-term picture of control.
      More evidence is required to prove that plasma glucose and glycosylated
      hemoglobin levels together gives a better estimate of glycemic control and
      compliance with treatment. Indian diabetes risk score (IDRS) is a simplified
      screening tool for identifying undiagnosed diabetic subjects, requires minimum
      time, and effort and can help to considerably reduce the costs of screening.
      OBJECTIVE: To study patterns of glycemic control using glycosylated hemoglobin in
      diabetic patients. To find out correlation between levels of plasma glucose and
      glycosylated hemoglobin in diabetics and to calculate IDRS of the study
      population. MATERIALS AND METHODS: A cross sectional study was conducted among
      300 known diabetic patients attending outpatient department of a rural medical
      college in Haryana, India. Following standard procedures and protocols FPG and
      glycosylated hemoglobin were measured to find out a pattern of glycemic control
      in them after taking their written and informed consent. A correlation between
      the levels of glycosylated hemoglobin and fasting blood glucose was also
      calculated. These patients were made to fill a performa and their demographic and
      clinical risk factors were noted and based on this, their IDRS was calculated.
      This was done to validate the IDRS in Indian rural population. RESULTS: Fifty-two
      percent of the population had fasting plasma glucose level between 125-150 mg/dl,
      21% had this level between 151-175 mg/dl. Thirteen percent of the study subjects
      had HbA1C between 6.5-7.5, more than half (57.3%) had this value between 7.5-8.5,
      12% and 18% had values between 8.5-9.5 and 9.5-10.5, respectively. Twelve percent
      of the participants had HbA1C level higher than 10.5. Correlation of fasting
      plasma glucose level and HbA1C was also studied and found that correlation
      coefficient came out to be .311. This correlation was found to be statistically
      significant (P = .007). Sixty-five percent of the case had IDRS higher than 60.
      CONCLUSIONS: Glycaemic control in diabetics can be better assessed with
      glycosylated hemoglobin and FPG together. A positive correlation between FPG and
      HbA1c allows for the use of HbA1c along with FPG in diagnosing type 2 DM but the
      two should not be used interchangeably. IDRS can be used as a screening tool for
      diabetes.

PMID- 21966152
TI  - Transvaginal ultrasonography in first trimester of pregnancy and its comparison
      with transabdominal ultrasonography.
AB  - OBJECTIVES: Examination of pregnant women in the first trimester with
      transvaginal ultrasonography with the aim to study various fetal development
      markers, e.g., gestation sac, yolk sac, fetal heart motion, CRL length, and fetal
      anatomy in both normal and abnormal pregnancies. Comparative evaluation of
      transvaginal ultrasonography vis-a-vis transabdominal scanning in the study of
      first trimester of pregnancy and its complications. To assess the relative merits
      and demerits of transvaginal ultrasonography in comparison with the
      transabdominal technique. MATERIALS AND METHODS: The study will be conducted on
      50 females patients during the first trimester of pregnancy. The study population
      will consist of both normal and abnormal pregnancies. These patients will be
      included on the basis of suspicion of or proven pregnancy of duration up to 12
      weeks from LMP. The evaluation of the patients will include the following: Record
      of patients obstetrical history and clinical examination, record of pregnancy
      test and relevant investigations, ultrasonic examination of pregnancy. (a)
      Transabdominal ultrasound scanning will be done with moderately distended bladder
      by using real time scanners with low frequency probe (3/3.5 MHz); (b)
      transvaginal sonography will be done with the real-time sector scanner using high
      frequency endovaginal probe (5/7.5 MHz), after the patient voids urine. Relevant
      images will be taken by using the multiformat automatic camera. RESULTS AND
      CONCLUSIONS: In the study of 46 normal intrauterine pregnancies, TVS showed
      additional information in 36 patients (78.3%) as compared to TAS, in detection of
      gestation sac, yolk sac, double bleb sign, or better visualization of embryonic
      anatomy. In the abnormal pregnancy (n=17), TVS provided more information in 11
      cases (64.9%), which included detection of embryonic demise, yolk sac, double
      bleb sign, or subchorionic hemorrhage. Regarding ectopic gestations (n=7), TVS
      gave additional information in 5 cases (71.4%) which included detection of
      ectopic fetal pole, yolk sac, decidual cast, adnexal mass, and fluid in cul de
      sac. In two cases, both TAS and TVS gave equal information. However, in 2 cases
      TAS demonstrated the extent of intraabdominal fluid better than TVS. The other
      advantages of TVS over TAS are that there is no need for the patient to have
      uncomfortably full bladder and time is saved from having to wait for bladder to
      fill. Thus, the potential preoperative patient can be kept fasting. TVS is also
      superior in obese patients, in patients with retroverted uterus and it also
      bypasses obstacles such as bone, gas filled bowel, and extensive pelvic
      adhesions. The limitations encountered with TVS were limited manoveuribility of
      probe and because of the unorthodox position and angle of the transducer, correct
      orientation was difficult initially.

PMID- 21966153
TI  - The relation between QT interval and T-wave variables in hypertensive patients.
AB  - BACKGROUND: The standard 12-lead ECG (electrocardiogram) continues to be the most
      frequently recorded noninvasive test in medicine. A prolonged ECG QT interval and
      Tpeak-Tend (Tpe) interval are predictors of ventricular arrhythmia and sudden
      cardiac death. AIM: The aim of this study is to analyze the relation between QT
      interval and T-wave variables in hypertensive patients, with and without left
      ventricular hypertrophy (LVH). MATERIALS AND METHODS: Fifty-nine consecutive
      patients with grade 2 essential hypertension were included in the study. They
      underwent standard 12-lead ECG, and QT intervals: QTmax (the maximal duration of
      the QT interval in the 12 ECG leads), QTc (heart rate corrected QTmax), QTm (mean
      QT interval), QTII (the QT interval in lead DII), QTcII (heart rate corrected
      QTII), and QTd (QT dispersion); and T-wave variables: T0e (T wave duration), T0em
      (mean T0e), Tpe, Tpem (mean Tpem), Ta (T wave amplitude), and Tam (mean Ta) were
      manually assessed. LVH was diagnosed using both echocardiography and the ECG
      criteria. RESULTS: QTc was prolonged in 41 patients (69%). Multiple regression
      analysis revealed a significant association between QT intervals and T-wave
      variables: QTmax and Tpe (P = 0.015), QTd and Tpe (P = 0.022) and Ta (P = 0.004),
      and Tpe with QTd and T0e (P < 0.05). A moderate but significant correlation was
      found between Tpe and QTmax, Tpe and QTII, and Ta and QTd. A prolonged QTc was
      more prevalent in hypertensive patients with LVH (85%), compared to hypertensive
      patients without LVH (50%). QTm, QTd, QTII, Tpe, Tpem were significantly elevated
      (P < 0.05) in patients with LVH. CONCLUSIONS: Hypertension is associated with an
      increased prevalence of prolonged QT intervals. QT intervals and T-wave variables
      are closely connected in hypertensive patients. QTm, T0em, Tpem, and Tam, do not
      provide significant additional information compared to QTmax, T0e, Tpe, and Ta.
      Left ventricular hypertrophy is associated with prolonged QT interval and Tpeak
      Tend interval in hypertensive patients.

PMID- 21966154
TI  - The prevalence of alcohol consumption among the students newly enrolled at a
      public university.
AB  - BACKGROUND: Alcohol is the number one toxic substance consumed by people of all
      age groups, which makes its use a public health problem. The overall trend shows
      that university students are those who suffer the most pressure. OBJECTIVE: To
      assess the prevalence of alcohol use among students newly enrolled at a public
      university in Alagoas, Brazil. MATERIALS AND METHODS: We conducted an analytical
      sectional study at the Federal University of Alagoas, with 1435 (44% of total)
      newly enrolled students of all courses in 2006. They answered a questionnaire
      based on the CAGE. Some points such as sex, age, marital status, course, housing,
      family characteristics and how drugs fit into in the student life were studied
      with the resources of EpiInfo version 3.3.2. The survey was approved by the
      Research Ethics Committee of the Federal University of Alagoas (number
      000878/2005-17). RESULTS: Of the group studied, 95.9% lived with family and 87.6%
      reported ever drinking alcohol at some time in their life. Of all the
      respondents, 55.4% of men reported having the habit of drinking with friends or
      colleagues (Odds = 0.71; CI = 0.58-0.88; P-value = 0.00088). Among all
      respondents, 17.7% of male students and 9.8% females skipped class after using
      alcohol (Odds = 0.52; CI = 0.38-0.72; P-value = 0.000023). The transition from
      adolescence to youth and study time at university is marked by greater
      vulnerability to alcohol abuse. The family is decisive for the initiation of
      alcohol use, and the university is a factor that increases the possibility of
      maintaining the practice. The fact that not all students were present in the
      classroom at the time of the application questionnaire may have limited the
      search because this was a sectional study. CONCLUSION: Alcohol consumption in
      this university is similar to that in other higher education institutions in the
      world, which is a cause for concern, since the external lesions are accentuated
      with the practice of using alcohol, characterizing the risk of violence.

PMID- 21966156
TI  - Role of phenolic compounds in peptic ulcer: An overview.
AB  - Peptic ulcer is the most common gastrointestinal tract (GIT) disorder in clinical
      practice, which affects approximately 5-10% of the people during their life. The
      use of herbal drugs for the prevention and treatment of various diseases is
      constantly developing throughout the world. This is particularly true with regard
      to phenolic compounds that probably constitute the largest group of plants
      secondary metabolites. Phenolic compounds have attracted special attention due to
      their health-promoting characteristics. In the past ten years a large number of
      the studies have been carried out on the effects of phenolic compounds on human
      health. Many studies have been carried out that strongly support the contribution
      of polyphenols to the prevention of cardiovascular diseases, cancer,
      osteoporosis, neurodegenerative diseases, and diabetes mellitus, and suggest a
      role in the prevention of peptic ulcer. Polyphenols display a number of
      pharmacological properties in the GIT area, acting as antisecretory,
      cytoprotective, and antioxidant agents. The antioxidant properties of phenolic
      compounds have been widely studied, but it has become clear that their mechanisms
      of action go beyond the modulation of oxidative stress. Various polyphenolic
      compounds have been reported for their anti-ulcerogenic activity with a good
      level of gastric protection. Besides their action as gastroprotective, these
      phenolic compounds can be an alternative for the treatment of gastric ulcers.
      Therefore, considering the important role of polyphenolic compounds in the
      prevention or reduction of gastric lesions induced by different ulcerogenic
      agents, in this review, we have summarized the literature on some potent
      antiulcer plants, such as, Oroxylum indicum, Zingiber officinale, Olea europaea
      L., Foeniculum vulgare, Alchornea glandulosa, Tephrosia purpurea, and so on,
      containing phenolic compounds, namely, baicalein, cinnamic acid, oleuropein,
      rutin, quercetin, and tephrosin, respectively, as active constituents.

PMID- 21966155
TI  - Endocannabinoid system in cardiovascular disorders - new pharmacotherapeutic
      opportunities.
AB  - The long history of Cannabis sativa had its development stimulated and oriented
      for medicine after the discovery and chemical characterization of its main active
      ingredient, the 9-tetrahydrocannabinol (9-THC). Consequently, a binding site for
      9-THC was identified in rat brains and the first cannabinoid receptor (CB1) was
      cloned, followed by the CB2 and by the discover of two endogenous agonists:
      anandamide and 2-arachidonoyl glycerol. Cannabinoid receptors, endocannabinoids
      and the enzymes that catalyze its synthesis and degradation constitute the
      endocannabinoid system (ECS), which plays an important role in the cardiovascular
      system. In vivo experiments with rats have demonstrated the action of anandamide
      and 2-AG on the development of atherosclerotic plaque, as well as an effect on
      heart rate, blood pressure, vasoactivity and energy metabolism (action in
      dyslipidemia and obesity). Recent studies with an antagonist of CB1 receptors
      showed that the modulation of ECS can play an important role in reducing
      cardiovascular risk in obese and dyslipidemic patients. Similarly, studies in
      rats have demonstrated the action of CB2 receptors in adhesion, migration,
      proliferation and function of immune cells involved in the atherosclerotic plaque
      formation process. The evidence so far gathered shows that the modulation of ECS
      (as agonism or antagonism of its receptors) is an enormous potential field for
      research and intervention in multiple areas of human pathophysiology. The
      development of selective drugs for the CB1 and CB2 receptors may open a door to
      new therapeutic regimens.This review article aims to address the key findings and
      evidences on the modulation of ECS, in order to prospect future forms of
      therapeutic intervention at the cardiovascular level. A recent, emerging,
      controversial and of undoubted scientific interest subject, which states as a
      potential therapeutic target to reach in the 21(st) century.

PMID- 21966157
TI  - Sociodemographic variables of contraceptive practice in Sikkim.
AB  - OBJECTIVES: The objective was to assess sociodemographic characteristics of men
      who use contraceptive and to compare them with men whose wives use contraceptive.
      MATERIALS AND METHODS:  STUDY DESIGN: A population-based cross-sectional study
      was performed. STUDY SETTING: It was performed in rural setting of the Sang PHC
      and Pakyong PHC service areas in Sikkim, India. STUDY PARTICIPANTS: A total of
      596 currently married men enrolled in the eligible couple registers.
      INTERVENTIONS: No interventions occurred. MEASUREMENTS: Sociodemographic
      correlates of contraceptive use were analyzed: occupation, religion, ethnicity,
      literacy, age, loss of children, and distance from health facility. RESULTS: The
      use of contraceptive was high among the cultivators - men (44.45%), spouse
      (36.01%) followed by persons in Government service, respectively, 31.49% and
      31.55%. Hindu men (55.42%), women (69.25%), and other backward communities (OBC)
      men (47.53%) and their wives (52.31%) were the majority users. A significantly
      higher number of users of contraceptive were literate men (72.33%) and their
      wives (86.17%) (chi(2)=0.021, P> 0.05). Highest use was found in men and women
      (44.47%) in the 35 years and above (43.83) age group. But this difference was not
      significant. With the increase in the number of losses of children the
      contraceptive use declined among men and their spouses. Contraceptive users were
      higher at distances 1 hour and above from the health center compared to others.
      CONCLUSIONS: The finding of the research indicated that sociodemographic
      correlates determine the magnitude of the contraceptive use among couples in a
      rural community. A research agenda should define factors at both macro and micro
      levels that interact to adversely impinge on reproductive health outcomes.

PMID- 21966158
TI  - Simultaneous determination of related substances of telmisartan and
      hydrochlorothiazide in tablet dosage form by using reversed phase high
      performance liquid chromatographic method.
AB  - OBJECTIVE: Telmisartan is a potent, long-lasting, nonpeptide antagonist of the
      angiotensin II type-1 (AT(1)) receptor that is indicated for the treatment of
      essential hypertension. Hydrochlorothiazide is a widely prescribed diuretic and
      it is indicated for the treatment of edema, control of essential hypertension and
      management of diabetes insipidus. In the current article a new, accurate,
      sensitive, precise, rapid, reversed phase high performance liquid chromatography
      (RP-HPLC) method was developed for determination of related substances of
      Telmisartan and Hydrochlorthiazide in tablet dosage form. MATERIALS AND METHODS:
      Simultaneous determination of related substances was performed on Kromasil C(18)
      analytical column (250 * 4.6 mm; 5MUm pertical size) column at 40 degrees C
      employing a gradient elution. Mobile phase consisting of solvent A (solution
      containing 2.0 g of potassium dihydrogen phosphate anhydrous and 1.04 g of Sodium
      1- Hexane sulphonic acid monohydrate per liter of water, adjusted to pH 3.0 with
      orthophosphoric acid) and solvent B (mixture of Acetonitrile: Methanol in the
      ratio 80:20 v/v) was used at a flow rate of 1.0 ml min(-1). UV detection was
      performed at 270 nm. RESULTS: During method validation parameter such as
      precision, linearity, accuracy, specificity, limit of detection and
      quantification were evaluated, which remained within acceptable limits.
      CONCLUSIONS: HPLC analytical method is linear, accurate, precise, robust and
      specific, being able to separate the main drug from its degradation products. It
      may find application for the routine analysis of the related substances of both
      Telmisartan and Hydrochlorthiazide in this combination tablets.

PMID- 21966159
TI  - Antinociceptive effect of an ethanolic extract of the aerial parts of Hilleria
      latifolia (Lam.) H. Walt. (Phytolaccaceae).
AB  - BACKGROUND: Hilleria latifolia (Lam.) H. Walt. (Phytolaccaceae) is a perennial
      herb used in Ghanaian traditional medicine for the treatment of various painful
      conditions. Little scientific evidence exists in literature on the effect of this
      plant on pain. MATERIALS AND METHODS: The present study examined the
      antinociceptive effect of the ethanolic extract of the aerial parts of H.
      latifolia in chemical (acetic acid-induced abdominal writhing, glutamate,
      formalin, and capsaicin tests) and thermal (tail immersion test) behavioral pain
      models in rodents. The possible mechanisms of the antinociceptive action were
      also assessed with various antagonists in the formalin test. RESULTS: The H.
      latifolia extract (HLE) together with morphine and diclofenac (positive
      controls), showed significant antinociceptive activity in all the models used.
      The antinociceptive effect exhibited by HLE in the formalin test was partly or
      wholly reversed by the systemic administration of naloxone, theophylline, and
      atropine. Glibenclamide, ondansetron, yohimbine, nifedipine, and N(G)-L-nitro
      arginine methyl ester (L-NAME), however, did not significantly block the
      antinociceptive effect of the extract. HLE, unlike morphine, did not induce
      tolerance to its antinociceptive effect in the formalin test after chronic
      administration; morphine tolerance did not also cross-generalize to HLE.
      Interestingly, also, the chronic concomitant administration of HLE and morphine
      significantly suppressed the development of morphine tolerance. CONCLUSION:
      Together, these results indicate that HLE produces dose-related antinociception
      in several models of chemical and thermal pain, without tolerance induction,
      through mechanisms that involve an interaction with adenosinergic, muscarinic
      cholinergic, and opioid pathways.

PMID- 21966160
TI  - Antidiabetic and antihyperlipidemic potential of Abelmoschus esculentus (L.)
      Moench. in streptozotocin-induced diabetic rats.
AB  - OBJECTIVES: The present investigation was aimed to study the antidiabetic and
      antihyperlipidemic potential of Abelmoschus esculentus peel and seed powder (AEPP
      and AESP) in streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS:
      Acute toxicity of AEPP and AESP was studied in rats at 2000 mg/kg dose and
      diabetes was induced in rats by administration of STZ (60 mg/kg, i.p.). After 14
      days of blood glucose stabilization, diabetic rats received AEPP, AESP, and
      glibenclamide up to 28 days. The blood samples were collected on day 28 to
      estimate the hemoglobin (Hb), glycosylated hemoglobin (HbA1c), serum glutamate
      pyruvate transferase (SGPT), total protein (TP), and lipid profile levels.
      RESULTS: In acute toxicity study, AESP and AESP did not show any toxicity or
      death up to a dose of 2000 mg/kg. Therefore, to assess the antidiabetic action,
      one by fifth and one by tenth dose of both powders were selected. Administration
      of AEPP and AESP at 100 and 200 mg/kg dose in diabetic rats showed significant (P
      < 0.001) reduction in blood glucose level and increase in body weight than
      diabetic control rats. A significant (P < 0.001) increased level of Hb, TP, and
      decreased level of HbA1c, SGPT were observed after the treatment of both doses of
      AEPP and AESP. Also, elevated lipid profile levels returned to near normal in
      diabetic rats after the administration of AEPP and AESP, 100 and 200 mg/kg dose,
      compared to diabetic control rats. CONCLUSION: The present study results, first
      time, support the antidiabetic and antihyperlipidemic potential of A. esculentus
      peel and seed powder in diabetic rats.

PMID- 21966161
TI  - Drug advertisements published in Indian Medical Journals: Are they ethical?
AB  - CONTEXT: It is observed in studies done for western medical journals that
      insufficient information related to drug is usually provided in the drug
      advertisements published in them. AIMS: As data for advertisements published in
      Indian Medical Journals were lacking, this study was designed with the aim of
      evaluating drug advertisements published in Indian Medical Journals for adequacy
      of information on drug and references given to support the claim made in the
      advertisements. SETTINGS AND DESIGN: Cross-sectional survey. METHODS AND
      MATERIALS: All medical journals related to clinical practice subscribed by the
      Central Library of Government Medical College, Surat, (Indian Journal of
      Pediatrics [IJP], Indian Pediatrics [IP], Journal of the Association of
      Physicians of India [JAPI], Journal of Indian Medical Association [JIMA], Indian
      Journal of Critical Care Medicine [IJCCM], Indian Journal of Medical and
      Pediatric Oncology [IJMPO], Indian Journal of Gastroenterology [IJG], Indian
      Journal of Ophthalmology [IJO], and Journal of Obstetrics and Gynecology of India
      [JOGI] were evaluated for adequacy of reporting of various parameters in drug
      advertisements published in these journals on the basis of "World Heath
      Organization (WHO)" criteria. References mentioned to support claims were also
      evaluated. STATISTICAL ANALYSIS USED: Descriptive statistics was used to describe
      data as frequencies, percentages, and 95% confidence interval around the
      percentage. RESULTS: Generic name was mentioned in 90% advertisements.
      Indications were mentioned in 84% advertisements. Dose, precautions, and
      contraindications were mentioned in 24%, 17%, and 16% advertisements,
      respectively. Adverse effects and postal address of pharmaceutical company was
      mentioned in 19% and 74% advertisements, respectively. Price was mentioned in
      only 5% advertisements. Only 28% claims were supported by references. Most common
      references were Journal articles (75%). CONCLUSION: Drug advertisements published
      in Indian Medical Journals are poor in reporting various parameters according to
      WHO criteria.

PMID- 21966162
TI  - Role of family and peers in the initiation and continuation of smoking behavior
      of future physicians.
AB  - BACKGROUND: Globally researchers have long back noted that the trend of substance
      use was on the rise particularly in the student population. OBJECTIVE: To find
      out the prevalence and determinants of smoking practices among undergraduate
      medical students. MATERIALS AND METHODS: A cross-sectional study was conducted
      among undergraduate medical (MBBS) students of a tertiary care medical college
      using a predesigned and pretested semi-structured self-administered anonymous
      questionnaire. RESULTS: Among 182 participants, 55 (30%) were smokers; 85.45%
      were regular smokers; majority in the age group 20-22 years (70%); mostly males
      (98%). No significant difference was observed among urban and rural students, and
      religion had no association. The practice of smoking for last 6 months to 1 year
      was in 43.6% and 40% smoked less than 6 months. Half of them (50.9%) smoked 5-9
      cigarettes per day. Peer pressure was significantly high in smokers (83.6%); 42%
      had other addictions. The effect of parental smoking on smoking habits of the
      participants was quite evident among smokers (82%), which was significantly
      higher than nonsmokers (chi(2) = 63.49, P < 0.05). Peer pressure was the most
      important risk factor (57.69%) of initiation of smoking habit followed by
      parental influence (16.49%). Among morbidities of smokers, 60.6% were suffering
      from regular cough, 6% from bronchitis, and 2% had asthma. CONCLUSIONS: Our
      survey conducted on budding doctors surprisingly showed that undergraduate
      medical students smoke so much.

PMID- 21966163
TI  - Study of antinociceptive activity of SSRI (fluoxetine and escitalopram) and
      atypical antidepressants (venlafaxine and mirtazepine) and their interaction with
      morphine and naloxone in mice.
AB  - OBJECTIVE: to study the probable site of antinociceptive action of SSRI
      (fluoxetine, escitalopram) and atypical antidepressants (mirtazapine,
      venlafaxine) and their interaction with morphine and naloxone. MATERIALS AND
      METHODS: the study was conducted on albino mice (25-35 grams) of either sex.
      Different doses of morphine (0.5 and 1 mg/kg), fluoxetine (2, 5 and 10 mg/kg),
      venlafaxine (30, 40 and 50 mg/kg), mirtazapine (3, 5 and 7 mg/kg) and
      escitalopram (2.5, 5 and 10 mg/kg) were administered subcutaneously to obtain
      their subanalgesic doses using tail flick analgesiometer. Tail flick latencies
      were obtained at 15, 30, 60 and 120 min. after drug administration. Naloxone (1
      mg/kg) was administered 10 minutes prior to test drug for testing antagonism.
      OBSERVATIONS: fluoxetine (5 and 10 mg/kg), mirtazapine (5 and 7 mg/kg) and
      venlafaxine (40 and 50 mg/kg) were found to have antinociceptive activity but not
      at lower doses. Escitalopram failed to show any antinociceptive activity at any
      of the doses used. The antinociceptive effect of all the drugs was antagonized by
      naloxone (1 mg/kg). Further, subanalgesic doses of fluoxetine, mirtazapine and
      venlafaxine showed analgesic activity with suboptimal dose of morphine (0.5
      mg/kg). RESULT AND CONCLUSION: fluoxetine, mirtazapine and venlafaxine have
      antinociceptive activity whereas escitalopram doesn't; their site of action seems
      to be the same as that of opioid analgesics ('mue' receptors). However, other
      pathways (cholinergic, histaminic, noradrenergic, GABAergic) may be involved in
      mediation of their analgesic activity, deserving further elucidation. Results
      apparently show that these drugs may be useful in the management of pain as
      monotherapy or in combination with other opioids.

PMID- 21966164
TI  - Dissolution behavior of beta-cyclodextrin molecular inclusion complexes of
      aceclofenac.
AB  - The objective of the present investigation was to study the effect of beta
      cyclodextrin (beta-CD) on the in vitro dissolution of aceclofenac (AF) from
      molecular inclusion complexes. Aceclofenac molecular inclusion complexes in 1:1
      and 1:2 M ratio were prepared using a kneading method. The in vitro dissolution
      of pure drug, physical mixtures, and cyclodextrin inclusion complexes was carried
      out. Molecular inclusion complexes of AF with beta-CD showed a considerable
      increase in the dissolution rate in comparison with the physical mixture and pure
      drug in 0.1 N HCl, pH 1.2, and phosphate buffer, pH 7.4. Inclusion complexes with
      a 1:2 M ratio showed the maximum dissolution rate in comparison to other ratios.
      Fourier transform infrared spectroscopy and differential scanning calorimetry
      studies indicated no interaction between AF and beta-CD in complexes in solid
      state. Molecular modeling results indicated the relative energetic stability of
      the beta-CD dimer-AF complex as compared to beta-CD monomer-AF. Dissolution
      enhancement was attributed to the formation of water soluble inclusion complexes
      with beta-CD. The in vitro release from all the formulations was best described
      by first-order kinetics (R(2) = 0.9826 and 0.9938 in 0.1 N HCl and phosphate
      buffer, respectively) followed by the Higuchi release model (R(2) = 0.9542 and
      0.9686 in 0.1 N HCl and phosphate buffer, respectively). In conclusion, the
      dissolution of AF can be enhanced by the use of a hydrophilic carrier like beta
      CD.

PMID- 21966166
TI  - Pharmacological screening of Coriandrum sativum Linn. for hepatoprotective
      activity.
AB  - OBJECTIVE: Coriandrum sativum (Linn.), a glabrous, aromatic, herbaceous annual
      plant, is well known for its use in jaundice. Essential oil, flavonoids, fatty
      acids, and sterols have been isolated from different parts of C. sativum. The
      plant has a very effective antioxidant profile showing 2,2-diphenyl-1
      picrylhydrazyl (DPPH) radical scavenging activity, lipoxygenase inhibition,
      phospholipid peroxidation inhibition, iron chelating activity, hydroxyl radical
      scavenging activity, superoxide dismutation, glutathione reduction and antilipid
      peroxidation due to its high total phenolic content with the presence of
      constituents like pyrogallol, caffeic acid, glycitin, etc. MATERIALS AND METHODS:
      This study was aimed at investigating the hepatoprotective activity of C. sativum
      against carbon tetrachloride (CCl4), with estimation of serum serum glutamyl
      oxaloacetic acid transaminase (SGOT), serum glutamyl pyruvate transaminase
      (SGPT), alkaine phosphatase (ALP) and bilirubin, and with liver histopathology.
      RESULTS: Ethanolic extract was found to be rich in alkaloids, phenolic compounds
      and flavonoids, and high performance liquid chromatography (HPLC) fingerprinting
      showed the presence of iso-quercetin and quercetin. C. sativum signifies
      hepatoprotection by reducing the liver weight, activities of SGOT, SGPT, and ALP,
      and direct bilirubin of CCl(4) intoxicated animals. Administration of C. sativum
      extract at 300 mg/kg dose resulted in disappearance of fatty deposit, ballooning
      degeneration and necrosis, indicating antihepatotoxic activity. CONCLUSION: The
      results of this study have led to the conclusion that ethanolic extract of C.
      sativum possesses hepatoprotective activity which may be due to the antioxidant
      potential of phenolic compounds.

PMID- 21966165
TI  - Development and characterization of nanosuspensions of olmesartan medoxomil for
      bioavailability enhancement.
AB  - BACKGROUND: Olmesartan medoxomil (OLM), an anti-hypertensive agent administered
      orally has absolute bioavailability of only 26% due to the poor aqueous
      solubility (<7.75 MUg/ml). The present investigation aimed at enhancing the oral
      bioavailability of OLM by improving its solubility and dissolution rate by
      preparing nanosuspensions. MATERIALS AND METHODS: The nanosuspensions of OLM were
      prepared using media milling technique followed by its lyophilization using
      mannitol as a cryoprotectant. Various formulation as well as process parameters
      were optimized in order to achieve desirable size and saturation solubility.
      Characterization of the prepared nanosuspension was done with respect to particle
      size, zeta potential, saturation solubility, dissolution rate, morphology study
      (TEM), in-vitro and exvivo drug diffusion study. Evaluation of the crystalline
      state before and after particle size reduction was done by differential scanning
      calorimetry (DSC) and powder X-ray diffraction (PXRD). RESULTS: The results
      indicated that the initial crystalline state is preserved following particle size
      reduction and that the saturation solubility, dissolution velocity and diffusion
      rate of the drug from the nanosuspension is significantly higher than that of the
      plain drug suspension as well as from the marketed tablet formulation.
      CONCLUSION: Nanosuspension seems to be a promising approach for bioavailability
      enhancement because of the simple method of its preparation and its universal
      applicability.

PMID- 21966167
TI  - Formulation and characterization of lipid-based drug delivery system of
      raloxifene-microemulsion and self-microemulsifying drug delivery system.
AB  - BACKGROUND: Raloxifene, a second-generation selective estrogen receptor modulator
      (SERM) used to prevent osteoporosis in postmenopausal women is administered
      orally in the form of a tablet. The absolute bioavailability of the drug is only
      2% because of extensive hepatic first-pass metabolism. Lipid-based formulations
      are reported to reduce the first-pass metabolism by promoting its lymphatic
      uptake. MATERIALS AND METHODS: In the present investigation, microemulsion and
      Self-Microemulsifying Drug Delivery System (SMEDDS) formulations of Raloxifene
      were prepared. The prepared formulations were characterized for drug loading,
      size, transparency, zeta potential, Transmission Electron Microscopy (TEM) and in
      vitro intestinal permeability. RESULTS: The results indicated that high drug
      loading, optimum size and desired zeta potential and transparency could be
      achieved with both SMEDDS and microemulsion. The TEM studies indicated the
      absence of aggregation with both the systems. The in vitro intestinal
      permeability results showed that the permeation of the drug from the
      microemulsion and SMEDDs was significantly higher than that obtained from the
      drug dispersion and marketed formulation. CONCLUSION: Lipid based formulations
      such as microemulsion and Self Microemulsifying drug delivery systems are
      expected to increase the oral bioavailability as evidenced by the increased
      intestinal permeation.

PMID- 21966168
TI  - Antihyperlipidemic and antiatherogenic activities of Terminalia pallida Linn.
      fruits in high fat diet-induced hyperlipidemic rats.
AB  - Hyperlipidemia contributes significantly in the manifestation and development of
      atherosclerosis and coronary heart disease (CHD). Although synthetic lipid
      lowering drugs are useful in treating hyperlipidemia, there are number of adverse
      effects. So the current interest has stimulated the search for new lipid-lowering
      agents with minimal side effects from natural sources. The present study was
      designed to investigate the antihyperlipidemic and antiatherogenic potentiality
      of ethanolic extract of Terminalia pallida fruits in high fat diet-induced
      hyperlipidemic rats. T. pallida fruits ethanolic extract (TPEt) was prepared
      using Soxhlet apparatus. Sprague-Dawley male rats were made hyperlipidemic by
      giving high fat diet, supplied by NIN (National Institute of Nutrition),
      Hyderabad, India. TPEt was administered in a dose of 100 mg/kg.b.w./day for 30
      days in high fat diet-induced hyperlipidemic rats. The body weights, plasma
      lipid, and lipoprotein levels were measured before and after the treatment. TPEt
      showed significant antihyperlipidemic and antiatherogenic activities as evidenced
      by significant decrease in plasma total cholesterol, triglycerides, low-density
      lipoprotein cholesterol, and very low-density lipoprotein cholesterol levels
      coupled together with elevation of high-density lipoprotein cholesterol levels
      and diminution of atherogenic index in high fat diet-induced hyperlipidemic rats.
      There was a significantly reduced body weight gain in TPEt-treated hyperlipidemic
      rats than in the control group. The present study demonstrates that TPEt
      possesses significant antihyperlipidemic and antiatherogenic properties, thus
      suggesting its beneficial effect in the treatment of cardiovascular diseases.

PMID- 21966169
TI  - Ethnic differences in the prevalence of polymorphisms in CYP7A1, CYP7B1 AND
      CYP27A1 enzymes involved in cholesterol metabolism.
AB  - It is well known that drug disposition and response are greatly determined by the
      activities of drug metabolizing enzymes, which are polymorphic. Some of these
      polymorphisms are clinically relevant and presented an ethnic-dependent pattern
      of distribution. The characterization of the genetic distribution of different
      populations allows the selection of therapeutic options in accordance with the
      genetic background, with the objective to avoid adverse reactions and inefficacy
      of the treatment. In this work, we studied selected genetic polymorphisms in drug
      metabolizing enzymes in three different ethnic groups - Portugal, Mozambique and
      Colombia. Polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP) genotyping methods were developed for drug metabolizing enzymes, namely,
      cholesterol 7alpha-hydroxylase (CYP7A1) (-203A>C, -346C>T, -496C>T, N233S,
      G347S), sterol 27-hydroxylase (CYP27A1) (R164W, A169V, D273N, V400A) and
      oxysterol 7alpha-hydroxylase (CYP7B1) (-116C>G, R324H, 1774C>T) to characterize
      the allelic distribution of these polymorphisms among three different
      ethnic/geographic origins. A total of 12 CYP7A1, CYP27A1 and CYP7B1 genetic
      variants were genotyped in a sample of 92 Portuguese, 151 Mozambican and 91
      Colombian subjects. The variants N233S in CYP7A1 and 1774C>T in CYP7B1 were not
      detected in any population studied. The promoter polymorphisms in CYP7A1 (
      203A>C, -346C>T, -496C>T) had high frequency in the three ethnic groups. G347S
      (CYP7A1), R164W, A169V and V400A (CYP27A1) were present in a low frequency but
      with a similar distribution in the three ethnic groups. Significant differences
      were observed for D273N (CYP27A1), -346C>T (CYP7A1), -116C>G and R324H
      (CYP7B1)Our results demonstrate a high variability of drug metabolizing enzymes
      between the different populations analyzed, indicating that at least some of
      these polymorphisms are ethnic specific.

PMID- 21966170
TI  - 2-Benzamido-3-(4-bromophenyl) acrylic acid.

PMID- 21966171
TI  - Fingolimod: The first oral drug approved by food and drug administration; A
      breakthrough in treatment of multiple sclerosis.

PMID- 21966172
TI  - Cure for HIV: New possibility on horizon.

PMID- 21966173
TI  - Periodontitis and rheumatoid arthritis: Inflammatory relationship.

PMID- 21966174
TI  - Nonsignificant P values cannot prove null hypothesis: Absence of evidence is not
      evidence of absence.

PMID- 21966175
TI  - Coenzyme Q10: The essential nutrient.

PMID- 21966176
TI  - Oral sex and oral cancer: A virus link.

PMID- 21966177
TI  - Oral health links breast cancer.

PMID- 21966178
TI  - The Transition to High School: Current Knowledge, Future Directions.
AB  - In the American educational system, school transitions are frequent and
      predictable, but they can disrupt student functioning across developmental
      domains. How students experience school transitions has been a focus of research
      for some time, but the high school transition has received less attention, and
      the limited research often focuses on a particular developmental domain (e.g.,
      academics and socioemotional well-being) to the exclusion of a more integrated
      model. This review relies on life course theory to establish an organizational
      framework for interpreting and connecting the diffuse and sometimes disparate
      findings on the high school transition, including adolescent developmental
      trajectories and the influence of social ties, changing sociocultural contexts,
      and stratification systems. Conclusions identify aspects for future inquiry
      suggested by current knowledge and the tenets of the life course perspective.

PMID- 21966179
TI  - Fatigue Scales and Chronic Fatigue Syndrome: Issues of Sensitivity and
      Specificity.
AB  - Few studies have explored issues of sensitivity and specificity for using the
      fatigue construct to identify patients meeting chronic fatigue syndrome (CFS)
      criteria. In this article, we examine the sensitivity and specificity of several
      fatigue scales that have attempted to define severe fatigue within CFS. Using
      Receiver Operating Characteristic (ROC) curve analysis, we found most scales and
      sub-scales had either significant specificity and/or sensitivity problems.
      However, the post-exertional subscale of the ME/CFS Fatigue Types Questionnaire
      (Jason, Jessen, et al., 2009) was the most promising in terms of specificity and
      sensitivity. Among the more traditional fatigue scales, Krupp, LaRocca, Muir
      Nash, and Steinberg's (1989) Fatigue Severity Scale had the best ability to
      differentiate CFS from healthy controls. Selecting questions, scales and cut off
      points to measure fatigue must be done with extreme care in order to successfully
      identify CFS cases.

PMID- 21966180
TI  - The Cognitive Predictors of Computational Skill with Whole versus Rational
      Numbers: An Exploratory Study.
AB  - The purpose of the present study was to explore the 3(rd)-grade cognitive
      predictors of 5th-grade computational skill with rational numbers and how those
      are similar to and different from the cognitive predictors of whole-number
      computational skill. Students (n = 688) were assessed on incoming whole-number
      calculation skill, language, nonverbal reasoning, concept formation, processing
      speed, and working memory in the fall of 3(rd) grade. Students were followed
      longitudinally and assessed on calculation skill with whole numbers and with
      rational numbers in the spring of 5(th) grade. The unique predictors of skill
      with whole-number computation were incoming whole-number calculation skill,
      nonverbal reasoning, concept formation, and working memory (numerical executive
      control). In addition to these cognitive abilities, language emerged as a unique
      predictor of rational-number computational skill.

PMID- 21966181
TI  - Darkness's descent on the American Anthropological Association. A cautionary
      tale.
AB  - In September 2000, the self-styled "anthropological journalist" Patrick Tierney
      began to make public his work claiming that the Yanomamo people of South America
      had been actively-indeed brutally-harmed by the sociobiological anthropologist
      Napoleon Chagnon and the geneticist-physician James Neel. Following a florid
      summary of Tierney's claims by the anthropologists Terence Turner and Leslie
      Sponsel, the American Anthropological Association (AAA) saw fit to take Tierney's
      claims seriously by conducting a major investigation into the matter. This paper
      focuses on the AAA's problematic actions in this case but also provides
      previously unpublished information on Tierney's falsehoods. The work presented is
      based on a year of research by a historian of medicine and science. The author
      intends the work to function as a cautionary tale to scholarly associations,
      which have the challenging duty of protecting scholarship and scholars from
      baseless and sensationalistic charges in the era of the Internet and twenty-four
      hour news cycles.

PMID- 21966182
TI  - Parenting Stress: A Comparison of Grandmother Caretakers and Mothers.
AB  - Parenting stress in grandmother caretakers has not been directly compared with a
      matched sample of mothers in the caretaker role. This study examined the main and
      interaction effects of caretaker status, employment, and race on parenting stress
      and whether these factors affect parenting stress in a convenience sample of
      grandmothers raising grandchildren (n = 86) and a sample of mothers of
      preschoolers (n = 86), matched for women's partner status, race, and employment.
      Grandmothers raising grandchildren reported more overall parenting stress and
      parental distress than mothers. Non-employed women reported more negative
      perceptions of their children and more difficult interactions with them. When
      controlling for contextual variables, grandmother caretakers showed greater
      parenting distress, but employment was not related to parenting stress. Being
      Caucasian and caretaking of older children affected overall parenting stress,
      parent-child interactions, and perceptions of one's children. Future research
      needs to consider the effect of outside influences on grandmothers' stress.

PMID- 21966183
TI  - In vitro assessment of shiitake mushroom (Lentinula edodes) extract for its
      antigingivitis activity.
AB  - Gingivitis is a preventable disease characterised by inflammation of the gums due
      to the buildup of a microbial biofilm at the gingival margin. It is implicated as
      a precursor to periodontitis, a much more serious problem which includes
      associated bone loss. Unfortunately, due to poor oral hygiene among the general
      population, gingivitis is prevalent and results in high treatment costs.
      Consequently, the option of treating gingivitis using functional foods, which
      promote oral health, is an attractive one. Medicinal mushrooms, including
      shiitake, have long been known for their immune system boosting as well as
      antimicrobial effects; however, they have not been employed in the treatment of
      oral disease. In the current study, the effectiveness of shiitake mushroom
      extract was compared to that of the active component in the leading gingivitis
      mouthwash, containing chlorhexidine, in an artificial mouth model (constant depth
      film fermenter). The total bacterial numbers as well as numbers of eight key taxa
      in the oral community were investigated over time using multiplex qPCR. The
      results indicated that shiitake mushroom extract lowered the numbers of some
      pathogenic taxa without affecting the taxa associated with health, unlike
      chlorhexidine which has a limited effect on all taxa.

PMID- 21966184
TI  - Prospective, randomized, fellow eye comparison of WaveLight Allegretto Wave Eye-Q
      versus VISX CustomVueTM STAR S4 IRTM in photorefractive keratectomy: analysis of
      visual outcomes and higher-order aberrations.
AB  - BACKGROUND: The purpose of this study was to compare differences in visual
      outcomes, higher-order aberrations, contrast sensitivity, and dry eye in patients
      undergoing photorefractive keratectomy using wavefront-guided VISX CustomVueTM
      and wavefront-optimized WaveLight((r)) Allegretto platforms. METHODS: In this
      randomized, prospective, single-masked, fellow-eye study, photorefractive
      keratectomy was performed on 46 eyes from 23 patients, with one eye randomized to
      WaveLight Allegretto, and the fellow eye receiving VISX CustomVue. Three-month
      postoperative outcome measures included uncorrected distance visual acuity,
      corrected distance visual acuity, refractive error, root mean square of total and
      grouped higher-order aberrations, contrast sensitivity, and Schirmer's testing.
      RESULTS: Mean values for uncorrected distance visual acuity (logMAR) were -0.03
      +/- 0.07 and -0.06 +/- 0.09 in the wavefront-optimized and wavefront-guided
      groups, respectively (P = 0.121). Uncorrected distance visual acuity of 20/20 or
      better was achieved in 91% of eyes receiving wavefront-guided photorefractive
      keratectomy, and 87% of eyes receiving wavefront-optimized photorefractive
      keratectomy, whereas uncorrected distance visual acuity of 20/15 was achieved in
      35% of the wavefront-optimized group and 64% of the wavefront-guided group (P >=
      0.296). While root mean square of total higher-order aberration, coma, and
      trefoil tended to increase in the wavefront-optimized group (P = 0.091, P =
      0.115, P = 0.459, respectively), only spherical aberration increased
      significantly (P = 0.014). Similar increases were found in wavefront- guided root
      mean square of total higher-order aberration (P = 0.113), coma (P = 0.403),
      trefoil (P = 0.603), and spherical aberration (P = 0.014). There was no
      significant difference in spherical aberration change when comparing the two
      platforms. The wavefront-guided group showed an increase in contrast sensitivity
      at 12 cycles per degree (P = 0.013). CONCLUSION: Both VISX CustomVue and
      WaveLight Allegretto platforms performed equally in terms of visual acuity,
      safety, and predictability in photorefractive keratectomy. The wavefront-guided
      group showed slightly improved contrast sensitivity. Both lasers induced a
      comparable degree of statistically significant spherical aberration, and tended
      to increase other higher-order aberration measures as well.

PMID- 21966185
TI  - In vivo and in vitro analysis of topographic changes secondary to DSAEK venting
      incisions.
AB  - INTRODUCTION: Descemet's stripping automated endothelial keratoplasty (DSAEK)
      venting incisions may induce irregular corneal astigmatism. The study examines in
      vivo and in vitro astigmatic effects of venting incisions. PATIENTS AND METHODS:
      In vivo analysis examined eleven eyes of eleven patients who had received DSAEK
      with venting incisions. A chart review of the eleven eyes including assessment of
      pre and postoperative refraction and topography was performed. In vitro analysis
      examined three cadaver eyes which received topographic imaging followed by
      venting incisions at 4 mm, 6 mm, and 7 mm optical zones. Topographic imaging was
      then performed again after the incisions. RESULTS: Postoperative topographies of
      eleven eyes demonstrated localized flattening at incision sites and cloverleaf
      pattern astigmatism. There was a significant difference in corneal irregularity
      measurement (P = 0.03), but no significant difference in shape factor or change
      of topographic cylinder. The cloverleaf pattern was found in cadaver eyes with
      incisions placed at 4 mm and 6 mm optical zones but not at the 7 mm zone.
      CONCLUSION: DSAEK venting incisions can cause irregular corneal astigmatism that
      may affect visual outcomes. The authors recommend placement of venting incisions
      near the 7 mm optical zone.

PMID- 21966186
TI  - Efficacy of a new prescription-only medical food supplement in alleviating signs
      and symptoms of dry eye, with or without concomitant cyclosporine A.
AB  - PURPOSE: To evaluate the effect of a new, prescription-only medical food
      supplement containing omega-3 and omega-6 essential fatty acids on dry eye signs
      and symptoms, with or without concomitant topical cyclosporine. METHODS: A total
      of 43 subjects were randomized and followed for 6 months. Group 1 (n = 23) was
      assigned to take two soft geltabs of the medical food supplement by mouth twice
      daily for 6 months. Group 2 (n = 20) was directed to take the medical food
      supplement in the same manner, along with topical cyclosporine, instilled twice
      daily during the last 3 months of the study. Subjects were evaluated at baseline,
      month 1, month 3, and month 6. Primary outcome measures included tear breakup
      time (TBUT), conjunctival staining, corneal staining, and change in subjective
      symptoms. RESULTS: Both groups had a statistically significant improvement in
      TBUT between baseline and month 6. In the food supplement only group, TBUT
      improved by 0.805 seconds from baseline to month 6. In the
      supplement/cyclosporine group, TBUT improved by 1.007 seconds from baseline.
      There was no statistically significant difference in TBUT between the two groups
      at baseline, month 3, or month 6. There were no significant differences in
      corneal or conjunctival staining between or within groups. Subjective symptoms
      were also improved in both groups. CONCLUSION: Supplementation with the proper
      balance of omega-3 and omega-6 essential fatty acids improved TBUT and relieved
      patient symptoms. The addition of topical cyclosporine did not convey any
      statistically significant improvement in TBUT beyond that achieved by the
      supplement.

PMID- 21966187
TI  - Perceived satisfaction of ophthalmology residents with the current Iranian
      ophthalmology curriculum.
AB  - OBJECTIVE: To assess the level of perceived satisfaction with the current Iranian
      ophthalmology curriculum in ensuring that residents acquire required competencies
      in various ophthalmology fields. METHODS: A closed-ended questionnaire was
      circulated to 100 residents or recently graduated ophthalmologists in Iran to
      measure their level of satisfaction about clinical conferences, journal clubs,
      scientific lectures, wet lab, simulation, evidence-based practice, and outpatient
      clinic and operating room training. They also cited the main barriers to a
      successful board exam. RESULTS: Ninety-nine questionnaires were completed and
      returned. Mean age of the responders was 31 +/- 4.56 years. A total of 36 (36.4%)
      responders expressed an overall satisfaction about the residency program, and 49
      (49.5%) did not feel happy about the state of teaching evidence-based decision
      making. They identified cataract surgery and eyeglass prescription as the most
      common regularly functioning modalities in their centers. The majority of the
      participants stated they have received appropriate training in cataract surgery
      (71%), but only 9% were satisfied with the provided training in glaucoma or
      vitreous and retinal surgery. Nevertheless, their overall satisfaction with their
      outpatient skills was good. CONCLUSION: The ophthalmologists felt quite confident
      in management of uncomplicated cases, especially cataract surgery at the level of
      general ophthalmology, but future studies can assess the effect of new practice
      based teaching methods on the residents' clinical training and eventually on
      patient care.

PMID- 21966188
TI  - Effect of five years of treatment with nipradilol eye drops in patients with
      normal tension glaucoma.
AB  - BACKGROUND: The purpose of this study was to evaluate the effects of topical
      nipradilol monotherapy for 5 years on intraocular pressure, visual field
      performance, and optic disk topography. METHODS: Thirty patients with normal
      tension glaucoma were monitored for intraocular pressure every 1-3 months. A
      Humphrey visual field test and measurement of optic disk configuration using the
      Heidelberg retina tomograph II was done after every year of treatment and the
      results compared with those before treatment. Visual field performance was also
      evaluated by trend and event analysis. RESULTS: The mean intraocular pressure +/-
      standard deviation after 3 years of nipradilol treatment (14.1 +/- 2.0 mmHg) and
      after 5 years of nipradilol treatment (13.7 +/- 2.1 mmHg) was significantly lower
      than that before treatment (17.0 +/- 1.8 mmHg, P < 0.0001). Heidelberg retina
      tomograph II parameters, such as mean cup depth and height variation contour
      after treatment, were significantly increased compared with those before
      treatment. Visual field performance worsened in eight eyes by trend analysis and
      eight eyes by event analysis. CONCLUSION: Nipradilol monotherapy was effective in
      reducing intraocular pressure over at least 5 years without worsening of optic
      disk topography. Furthermore, mean cup depth and height variation contour were
      also significantly improved. However, visual field performance worsened in 16.0%
      of patients with normal tension glaucoma.

PMID- 21966189
TI  - Intravitreal bevacizumab for delayed radiation maculopathy and papillopathy after
      irradiation for maxillary sinus cancer.
AB  - BACKGROUND: The evaluation of intravitreal bevacizumab treatment for delayed
      radiation maculopathy and papillopathy after irradiation for maxillary sinus
      cancer. CASE REPORT: A patient with radiation maculopathy and papillopathy was
      treated with intravitreal bevacizumab (1.25 mg). Main outcome measures included
      fundus photography, angiography, and optical coherence tomography (OCT). Two
      weeks after intravitreal bevacizumab, visual acuity improved from 0.4 to 1.2.
      Fundus examination revealed decreased disc swelling, peripapillary hemorrhage,
      and macular edema. OCT demonstrated complete resolution of serous retinal
      detachment. At the 12-month follow-up, there was no exudation recurrence. No
      ocular or systemic side effects were observed. CONCLUSION: Intravitreal
      bevacizumab can be used to treat radiation maculopathy and papillopathy.
      Antivascular endothelial growth factor therapy may decrease tissue injury
      associated with radiation vasculopathy.

PMID- 21966190
TI  - Bilateral total Descemet's membrane detachments after strangulation.
AB  - The eyes of a 25-year-old male were collected by the Utah Lions Eye Bank after
      his suicide by hanging. Following dissection of the corneoscleral buttons from
      intact globes, bilateral detached Descemet's membranes with subsequent scrolling
      in the periphery were observed. We believe these findings were caused by a large
      increase in intraocular pressure secondary to the hanging. Lens and anterior
      capsule fractures after hanging have been reported, but corneal damage has never
      been discussed. We invite transplant surgeons and eye bank recovery specialists
      to share their experience of similar corneal changes in donated eyes following
      strangulation or hanging.

PMID- 21966191
TI  - Four cases of traumatic hypotony maculopathy treated by various methods.
AB  - Several reports have been published on methods for treating hypotony maculopathy.
      Currently, the preferred choice of treatment depends on the severity of the
      illness. We experienced four cases of traumatic hypotony maculopathy and treated
      them by various methods. Cases 1-3 were treated by various surgical treatments.
      Case 1 was treated by combined cataract surgery and pars plana vitrectomy. The
      vitreous cavity was replaced with 20% sulfur hexafluoride (SF6). Case 2 did not
      improve with laser trabeculoplasty, so further encircling was performed. Case 3
      did not improve with photocoagulation of the ciliary body and injection of 20%
      SF6 into the vitreous cavity. Consequently, this case required suturing of the
      ciliary body to the sclera, cryopexy for the ciliary body, and injection of 100%
      SF6. Case 4 was treated only with eye drops. Intraocular pressure (IOP) increased
      in all cases as a result of treatment. Treatment improved hypotony maculopathy in
      all cases. Pre-treatment visual acuities ranged from 0.03 to 0.4, with IOP
      ranging from 2 to 10 mmHg. Post-treatment visual acuity ranged from 0.09 to 1.2,
      with IOP ranging from 14 to 16 mmHg. Only case 2 resulted in poor visual
      prognosis because of choroidal rupture near the foveola. The difficulty in
      choosing treatment methods lies in the need for multiple surgical treatments for
      some cases. Effective and noninvasive treatment methods are expected to be
      established in the future.

PMID- 21966192
TI  - Two-position measurement of intraocular pressure by PT100 noncontact tonometry in
      comparison with Goldmann tonometry.
AB  - BACKGROUND: The purpose of this study was to evaluate the precision of
      intraocular pressure measurements obtained by PT100 noncontact tonometry in a
      handheld and slit lamp-mounted position in comparison with that of Goldmann
      applanation tonometry in healthy young adults. METHODS: Sixty eyes from 60
      subjects (30 men and 30 women) aged 22 +/- 1 (range 20-24) years participated in
      this study. Triplicate intraocular pressure measurement of a randomly selected
      eye was obtained by a noncontact tonometer in a handheld and slit lamp-mounted
      position in a randomized order, with the Goldmann applanation tonometer always
      performed last. A second measurement session was carried out after one week to
      assess repeatability. RESULTS: The mean +/- standard deviation of intraocular
      pressure readings in the first and second session, respectively, with the three
      techniques were: handheld position, 14.52 +/- 3.28 mmHg and 15.26 +/- 2.11 mmHg;
      slit lamp-mounted position, 14.01 +/- 2.80 mmHg and 15.16 +/- 2.34 mmHg; and
      Goldmann applanation tonometer, 14.86 +/- 3.26 mmHg and 15.16 +/- 2.42 mmHg.
      There were no significant differences (P > 0.05) between the techniques in the
      intraocular pressure measurements returned (Goldmann applanation tonometer vs
      handheld and Goldmann applanation tonometer vs slit lamp-mounted). The Goldmann
      applanation tonometer measured intraocular pressure 0.34 mmHg higher than
      handheld and 0.85 mmHg higher than slit lamp-mounted in session 1, and in session
      2 Goldmann applanation tonometer intraocular pressure measurement was the same as
      with the slit lamp-mounted method but lower than with the handheld method by 0.11
      mmHg. In PT100 handheld vs slit lamp-mounted comparisons, there were no
      significant differences (P > 0.05) between intraocular pressure measurements
      returned by both techniques in sessions 1 and 2. Intrasession and intersession
      repeatability coefficients for Goldmann applanation tonometer intraocular
      pressure and slit lamp-mounted intraocular pressure were similar, and better in
      comparison with those for handheld intraocular pressure. CONCLUSION: The Goldmann
      applanation tonometer and PT100 noncontact tonometer in both positions studied
      here are reliable, consistent techniques for measurement of intraocular pressure,
      and can be used interchangeably for obtaining intraocular pressure values in
      young normal subjects. Repositioning of the PT100 tonometer from hand-held to
      slit lamp-mounted improved its precision and reduced variation with respect to
      the Goldmann applanation tonometer.

PMID- 21966193
TI  - Case of acute zonal occult outer retinopathy with abnormal pattern visual evoked
      potentials.
AB  - Electrophysiological and morphological findings were studied in a case of acute
      zonal occult outer retinopathy (AZOOR) showing abnormal pattern visual evoked
      potentials (VEPs) at the onset and significant functional recovery in the natural
      course. A 21-year-old woman presented with acute onset of photopsia and a large
      scotoma in the right eye of 2 weeks duration. Her visual acuity was 20/20 in both
      eyes with no ophthalmoscopic and fluorescein angiographic abnormalities. However,
      a relative afferent pupillary defect and an enlarged blind spot were found in the
      right eye. The pattern VEPs were severely reduced when the right eye was
      stimulated. The amplitudes of both rod and cone full-field electroretinographics
      (ERGs) were reduced in the right eye. The amplitudes of the multifocal ERGs were
      reduced in the area of the enlarged blind spot. Irregularities in the inner
      segment/outer segment (IS/OS) line of the photoreceptors were observed over the
      nasal fovea by optical coherence tomography (OCT). The patient was followed
      without treatment. The enlarged blind spot disappeared in 3 months after the
      onset. At 5 months, reappearance of the IS/OS line was detected by OCT. At 6
      months, the P(100) recovered to normal values. At 1 year, the reduced full-field
      ERGs were almost normal size and the multifocal ERGs in the area corresponding to
      the enlarged blind spot were also improved. ERG findings are crucial for
      differentiating AZOOR from retrobulbar neuritis, especially in patients with
      abnormal pattern VEPs. The pattern VEPs, full-field ERGs, multifocal ERGs, and
      OCT images can be abnormal in the early phase of AZOOR, but they can all improve
      during the natural course.

PMID- 21966194
TI  - Evaluation of the American Society of Cataract and Refractive Surgery intraocular
      lens calculator for eyes with prior radial keratotomy.
AB  - BACKGROUND: The purpose of this study was to evaluate the American Society of
      Cataract and Refractive Surgery (ASCRS) intraocular lens (IOL) calculator for
      eyes with prior radial keratotomy and assess the accuracy of its methods in
      predicting IOL power in patients with previous radial keratotomy. METHODS: This
      retrospective study included data from 15 eyes with previous radial keratotomy
      and subsequent cataract surgery. The average central power and Humphrey Atlas
      methods from the ASCRS IOL calculator, along with an average IOL power produced
      from an average of these two methods (ASCRS average), were compared. Primary
      outcome measures for each method were mean arithmetic and absolute IOL prediction
      error, variance in mean arithmetic IOL prediction error, and the percentage of
      refractive outcomes within +/-0.50, +/-1.00, +/-1.50, and +/-2.00 diopters (D).
      RESULTS: The average central power method and the ASCRS average were
      significantly more accurate than the Humphrey Atlas method in terms of mean
      absolute IOL prediction error (1.03 D and 1.02 D versus 1.53; P = 0.04 and P =
      0.01, respectively). In addition, the average central power method and ASCRS
      average produced a higher percentage of refractive outcomes within +/-0.50 D when
      compared with the Humphrey Atlas method (60% and 46.67% versus 0%, respectively).
      A comparison of the average central power method and the ASCRS average
      demonstrated a smaller variance and higher percentage of patients within +/-1.00
      D when using the ASCRS average. CONCLUSION: The ASCRS calculator for eyes with
      prior radial keratotomy is an easily accessible and valuable online tool for
      calculating IOL power in patients with previous radial keratotomy. We found that
      the ASCRS average produced by the calculator provided the best IOL prediction. We
      recommend using it with the addition of 1.00 to 1.50 D to its IOL power
      prediction.

PMID- 21966195
TI  - Basic training module for vitreoretinal surgery and the Casey Eye Institute
      Vitrectomy Indices Tool for Skills Assessment.
AB  - BACKGROUND: The purpose of this study was to design and implement a vitreoretinal
      training module that would be useful for ophthalmology residents and fellows to
      learn the basic maneuvers required in vitreoretinal surgery. METHODS: A
      prospective pilot study evaluating the training module was undertaken in 13
      ophthalmology trainees (residents and vitreoretinal fellows) with varying levels
      of vitreoretinal training experience. A vitreoretinal training module was
      designed and consisted of a three-port vitrectomy setup (sclerotomy wound
      construction, infusion placement), intraocular tasks (core vitrectomy, driving
      the operating microscope, membrane peel, air-fluid exchange), and wound closure.
      Standard vitrectomy instrumentation, the VitRet eye (Phillips Studio, Bristol,
      UK) and vitreous-like fluid using dairy creamer and balanced saline were
      utilized. A five-point Likert scale, ie, the Casey Eye Institute Vitrectomy
      Indices Tool for Skills Assessment (CEIVITS), was devised to evaluate each
      component of the module. Vitreoretinal surgical maneuvers were digitally recorded
      and graded by an attending vitreoretinal surgeon. Linear regression and
      correlation were performed to evaluate the relationship between prior
      vitreoretinal experience and CEIVITS performance. The main outcome measures were
      correlation of vitreoretinal surgical experience and CEIVITS performance on
      simulated tasks using a basic vitreoretinal training module. RESULTS: Thirteen
      participants from postgraduate year 2 to postgraduate year 6 levels were
      evaluated. Nine participants were male and four were female. The median age of
      participants was 32 (range 30-36) years and surgical experience was 0-410 prior
      vitreoretinal surgical procedures. A positive correlation (P < 0.05) was observed
      between vitreoretinal surgical experience and CEIVITS performance on the
      following tasks: total score (P = 0.021), sclerotomy wound construction (P =
      0.047), infusion line placement (P = 0.012), air-fluid exchange (P = 0.004), and
      wound closure (P = 0.032). Post module surveys showed that the majority of
      trainees felt that the vitreoretinal training module improved their understanding
      of vitreoretinal surgery. The nonbiohazardous nature of the setup was
      advantageous from sanitation and cost perspectives. CONCLUSION: The
      implementation of our training module for residency and vitreoretinal fellowship
      was feasible and the CEIVITS adequately assessed basic vitrectomy maneuvers.
      Given that ophthalmologic and subspecialty instruction migrates from an
      apprenticeship to a competency-based model, the face and content validity makes
      the CEIVITS module a promising one in vitreoretinal surgical instruction.

PMID- 21966196
TI  - Poststreptococcal keratouveitis associated with group C streptococcus
      pharyngitis.
AB  - PURPOSE: To report the first case of poststreptococcal syndrome uveitis (PSU) in
      association with group C streptococcus (GCS). PATIENTS AND METHODS: Chart review
      of a 24-year-old man who presented with bilateral ocular redness, pain, and
      photophobia for 5 days and "white rings" around his eyes for a duration of 3
      days. The patient further reported fever and sore throat in the preceding week.
      Slit-lamp examination showed bilateral keratouveitis. A thorough uveitis workup,
      antistreptolysin O (ASLO) titer, and throat culture were obtained. The patient
      was treated with frequent topical steroids and systemic doxycycline. The uveitis
      and keratitis subsided over the next few weeks, leaving extensive peripheral
      keratolysis. RESULTS: The results of laboratory diagnostic testing revealed an
      elevated ASLO, C-reactive protein, as well as HLA-B27 positivity. Throat cultures
      grew beta-hemolytic GCS; group A streptococcus was culture negative. CONCLUSION:
      GCS pharyngitis may be a causative organism of PSU.

PMID- 21966197
TI  - Ocular injuries among industrial welders in Port Harcourt, Nigeria.
AB  - BACKGROUND: The purpose of this study was to determine the prevalence and pattern
      of ocular injuries among industrial welders and rate the use of protective
      eyewear at work among industrial welders in Port Harcourt. Information from this
      study will provide a database for effective policy formation on prevention of
      occupational eye injuries in Port Harcourt Rivers State. METHODS: A cross
      sectional survey of ocular injuries and use of protective eyewear among
      industrial welders in the Port Harcourt local government area of Rivers State,
      Nigeria, was carried out over a three-month period. Five hundred welders were
      selected by simple random sampling. Information was obtained using an interviewer
      administered questionnaire. All welders were examined in their workshops.
      RESULTS: Flying metal chips were the chief source of ocular injury, as reported
      by 199 (68.15%) of those who gave a history of work-related eye injury, while arc
      rays accounted for the remaining 93 (31.85%). There was a high level of awareness
      of the risk of sustaining an eye injury from welding (n = 490, 98%), but only 46
      (15.3%) of the welders were using protective eyewear at the time of injury.
      CONCLUSION: To minimize ocular injury and promote eye health amongst industrial
      welders, safety intervention programs, such as awareness campaigns, setting up of
      targeted programs by the relevant government agencies, and encouragement of
      locally produced eye protectors is recommended. The involvement of occupational
      medical practitioners is also strongly recommended.

PMID- 21966198
TI  - Outcome of penetrating keratoplasty in corneal ulcer: a single-center experience.
AB  - BACKGROUND: Corneal ulcers often lead to scarring and astigmatism, and
      significant loss of vision is a common consequence. OBJECTIVE: To determine the
      rate of graft rejection, one of the most serious concerns with this procedure,
      and to evaluate the recovery of visual function in those patients for whom the
      operation was successful. METHODS: We describe a retrospective study of 33
      corneal ulcer patients undergoing penetrating keratoplasty (PK) at the Tabriz
      Nikookari Eye Hospital. RESULTS: Mean age of the patients was 44 +/- 14 years.
      Most common risk factors for active keratitis were trauma, dry eye, and
      malnutrition. Culture-positive results included bacterial keratitis (n = 15) and
      fungal keratitis (n = 5). Perforation was a significant risk factor for
      therapeutic failure (P < 0.05). Age or gender had no statistically significant
      effects on the PK outcome (P > 0.05). Postoperative visual acuity had a
      significant association with preoperative visual acuity (P < 0.01). Graft
      rejection rate (27.2%) was similar to that reported in the literature.
      CONCLUSION: Although lamellar keratoplasty has recently been established, there
      are practical reasons for continuing the use of PK in centers such as ours, with
      due attention to the requirement for topical immunosuppression to diminish the
      rate of graft rejection and antimicrobial treatment to prevent postoperative
      infection.

PMID- 21966199
TI  - The Mozart effect in biofeedback visual rehabilitation: a case report.
AB  - PURPOSE: To evaluate the usefulness of acoustic biofeedback by means of Mozart's
      Sonata for Two Pianos in D Major K. 448 to maintain and/or restore visual
      performance in a patient with macular pucker and glaucoma. METHODS: A 74-year-old
      patient with open angle glaucoma in both eyes and macular pucker in the right eye
      (RE) underwent visual rehabilitation with acoustic biofeedback by means of the
      MAIATM Vision Training Module (Centervue, Padova, Italy) 10 minutes each eye once
      a week for 5 weeks. The patient was asked to move his eyes according to a sound
      which changed into Mozart's Sonata for Two Pianos when the patient locked the
      fixation target. RESULTS: Best-corrected visual acuity improved in his right eye
      (RE) and was stable in the left eye (LE). Fixation stability improved in both
      eyes, and retinal sensitivity decreased in the RE and improved in the LE. The
      characteristic of the macular pucker did not change during the training as
      demonstrated with optical coherence tomography. The patient was very satisfied
      with the training, as demonstrated by a 25-item questionnaire (National Eye
      Institute - Visual Functioning Questionnaire, NEI-VFQ-25). The patient's reading
      speed and the character size which he was able to read improved in his RE.
      CONCLUSION: Music could enhance synaptic plasticity and affect neural learning
      and fixation training by means of MAIA vision training. Therefore it can improve
      visual performance in patients with macular pucker, postpone the surgical time,
      and assure a better quality of life for the patient.

PMID- 21966200
TI  - Q fever: a new ocular manifestation.
AB  - Q Fever is a zoonosis caused by Coxiella burnetii. Ocular manifestations are rare
      in this infection. We describe the case of a man complaining of an intense retro
      orbital headache, fever, arthralgia, and bilateral loss of vision, who showed an
      anterior uveitis accompanied by exudative bilateral inferior retinal detachment
      and optic disk edema. At the beginning, a Vogt-Koyanagi-Harada (VKH) syndrome was
      suspected, but the patient was diagnosed with Q fever and treatment with
      doxycycline was initiated, with complete resolution after 2 weeks. We wondered if
      Q fever could unleash VKH syndrome or simulate a VKH syndrome by a similar
      immunological process.

PMID- 21966201
TI  - Corneal collagen crosslinking in the treatment of infectious keratitis.
AB  - PURPOSE: To report the use of corneal collagen crosslinking in the treatment of
      infective keratitis not responding to antimicrobial therapy. METHODS: Two
      retrospective case reports of infective keratitis treated with corneal collagen
      crosslinking. RESULTS: In both cases, corneal collagen crosslinking caused a
      rapid resolution of the infective keratitis, leaving residual stromal scarring.
      Due to the density of scarring, one case required subsequent penetrating
      keratoplasty for visual rehabilitation. CONCLUSION: Corneal collagen crosslinking
      is a promising new technique for the management of infective keratitis not
      responding to antimicrobial therapy. Further elucidation of its safety and role
      in management of infectious keratitis is needed by way of future studies.

PMID- 21966202
TI  - Predicting the necessity of LASIK enhancement after cataract surgery in patients
      with multifocal IOL implantation.
AB  - PURPOSE: To investigate if the parameters measured routinely prior to cataract
      surgery with multifocal intraocular lens (IOL) implantation can predict the
      necessity of additional laser in situ keratomileusis (LASIK) to improve visual
      outcome. METHODS: Records of patients undergoing cataract surgery between January
      2008 and December 2009 were reviewed. Individuals satisfied with visual outcome
      of cataract surgery and not satisfied were grouped (group 1 and 2, respectively).
      Preoperative data of refractive error, axial length, corneal astigmatism,
      intraocular pressure, and postoperative uncorrected visual acuity were recorded.
      Data was available for 62 patients (104 eyes), of which LASIK enhancement was
      deemed necessary in 21 eyes (20%; group 2). The receiver operator characteristic
      curves were used to discriminate between the groups and linear regression
      analysis was performed to predict the postoperative visual outcome. RESULTS: The
      astigmatism measured preoperatively using manifest refraction had an accuracy of
      64% in discriminating between the groups. Age, spherical component of refraction,
      axial length, corneal astigmatism, and intraocular pressure were very close to
      chance prediction 59%, 57%, 56%, 51%, and 51%, respectively. The postoperative
      uncorrected visual acuity had an accuracy of 79% in discriminating the groups.
      Individuals with uncorrected visual acuity worse than 20/40 after cataract
      surgery were most likely to undergo LASIK enhancement; however, approximately 20%
      of group 2 underwent LASIK enhancement despite having visual acuity of 20/30 or
      better. When combined, preoperative visual acuity accounted for just 7% of
      variance in postoperative uncorrected visual acuity. CONCLUSION: Requirement of
      LASIK enhancement after cataract surgery with multifocal IOL implant is complex
      in nature, and parameters routinely measured before surgery cannot successfully
      identify the group requiring LASIK enhancement or predict postoperative
      uncorrected visual acuity.

PMID- 21966203
TI  - Evaluating botulinum toxin products for clinical use requires accurate, complete,
      and unbiased data.

PMID- 21966204
TI  - Update and optimal use of a brinzolamide-timolol fixed combination in open-angle
      glaucoma and ocular hypertension.
AB  - Glaucoma encompasses a wide clinical spectrum of disease, with the common
      pathophysiology of progressive optic neuropathy leading to visual field loss.
      Elevated intraocular pressure (IOP) is a key risk factor in disease progression.
      Treatment is aimed at reduction of IOP to minimize continued optic nerve head
      damage. Pharmacologic treatment with various classes of IOP-lowering medications
      is generally employed before more aggressive surgical interventions. Monotherapy
      is generally accepted as initial therapy for glaucoma, but at least half of
      patients may require more than one IOP-lowering medication. One option is the
      fixed combination of brinzolamide 1% and timolol maleate 0.5%, which is
      commercially available in some countries as Azarga((r)) for treatment of glaucoma
      not adequately responsive to monotherapy. These agents may also be used in an
      unfixed fashion, but fixed combination therapy is generally more convenient for
      patients, which may result in improved compliance, a reduction of the "washout
      effect" from instilling multiple drops, and a potential reduction in the side
      effects related to multiple doses of preservatives.

PMID- 21966205
TI  - Hearing disability in patients with Fuchs' endothelial corneal dystrophy:
      unrecognized co-pathology?
AB  - PURPOSE: To investigate a possible association between Fuchs' endothelial corneal
      dystrophy (FECD) and hearing disability. METHODS: A cross-sectional observational
      study was performed at the University Medical Center Utrecht. Cases and controls
      were patients who were treated by a cornea specialist between 2004 and 2008. FECD
      patients had either already undergone or were planned for a keratoplasty
      procedure. All controls were patients treated for cataract without any corneal
      pathology. Cases and controls were matched by age group and gender. A structured
      telephone interview combined with a validated self-perceived hearing function
      test (the Hearing Handicap Inventory for the Elderly, screening version; HHIE-S)
      was used for data collection. RESULTS: Hearing disability was reported in 33
      patients (45.8%) in the FECD-group (n = 72, average age: 73 years) versus 50
      patients (34.7%) in the control group (n = 144, average age: 73 years). Hearing
      disability was significantly associated with FECD after adjustment for age, noise
      exposure, and diabetes mellitus (odds ratio 1.97 95% confidence interval 1.04
      3.75). CONCLUSION: This case-control study reports a significant association
      between FECD and hearing disability. The causal relation was not evaluated in
      this study, though mutations in the SLC4A11 gene could have played an important
      role. This gene encodes for an ion transporter, which has been found in the
      cornea and inner ear. With the lack of examination with a pure tone or speech
      audiometry in this study, further studies need to be performed in order to
      support the association and should include a complete ENT examination with
      audiometry and genetic research.

PMID- 21966206
TI  - Ranibizumab in the treatment of patients with visual impairment due to diabetic
      macular edema.
AB  - Diabetic macular edema is the major cause of visual acuity impairment in diabetic
      patients. The exact etiopathogenesis is unknown and, currently, grid/focal
      retinal laser photocoagulation represents the recommended treatment. It has been
      demonstrated that vascular endothelial growth factor (VEGF) plays a key role in
      the pathogenesis of diabetic macular edema by mediating vascular permeability and
      accumulation of intracellular and extracellular fluid, and thereby represents an
      appealing candidate as a therapeutic target for the treatment of diabetic macular
      edema. The advent of intravitreal anti-VEGF drugs has opened up a new era for the
      management of diabetic macular edema. At present, three anti-VEGF substances are
      available for routine clinical use, ie, pegaptanib, ranibizumab, and bevacizumab.
      The aim of this review is to summarize the evidence supporting the use of
      ranibizumab in clinical practice. Most of the studies analyzed in this review are
      prospective, controlled clinical trials that have focused on documenting the
      therapeutic effect of ranibizumab and its safety, providing encouraging results.

PMID- 21966208
TI  - Erratum: corrigendum.
AB  - [This corrects the article on p. 1151 in vol. 5, PMID: 21887098.].

PMID- 21966207
TI  - Oral voclosporin: novel calcineurin inhibitor for treatment of noninfectious
      uveitis.
AB  - Voclosporin, a novel immunomodulatory drug inhibiting the calcineurin enzyme, was
      developed to prevent organ graft rejection and to treat autoimmune diseases. The
      chemical structure of voclosporin is similar to that of cyclosporine A, with a
      difference in one amino acid, leading to superior calcineurin inhibition and less
      variability in plasma concentration. Compared with placebo, voclosporin may
      significantly reduce inflammation and prevent recurrences of inflammation in
      patients with noninfectious uveitis. Future studies have to show if these
      advantages are accompanied by greater clinical efficacy and fewer side effects
      compared with the classic calcineurin inhibitors.

PMID- 21966209
TI  - Erratum: corrigendum.
AB  - [This corrects the article on p. 1095 in vol. 5, PMID: 21887088.].

PMID- 21966210
TI  - A computer-based anaglyphic system for the treatment of amblyopia.
AB  - PURPOSE: Virtual reality (VR)-based treatment has been introduced as a potential
      option for amblyopia management, presumably without involving the problems of
      occlusion and penalization, including variable and unsatisfactory outcomes, long
      duration of treatment, poor compliance, psychological impact, and complications.
      However, VR-based treatment is costly and not accessible for most children. This
      paper introduces a method that encompasses the advantages of VR-based treatment
      at a lower cost. METHODS: The presented system consists of a pair of glasses with
      two color filters and software for use on a personal computer. The software is
      designed such that some active graphic components can only be seen by the
      amblyopic eye and are filtered out for the other eye. Some components would be
      seen by both to encourage fusion. The result is that the patient must use both
      eyes, and specifically the amblyopic eye, to play the games. RESULTS: A prototype
      of the system, the ABG InSight, was found capable of successfully filtering out
      elements of a certain color and therefore, could prove to be a viable alternative
      to VR-based treatment for amblyopia. CONCLUSION: The anaglyphic system maintains
      most of the advantages of VR-based systems, but is less costly and highly
      accessible. It fulfills the means that VR-based systems are designed to achieve,
      and warrants further investigation.

PMID- 21966211
TI  - Prevalence and causes of blindness at a tertiary hospital in Douala, Cameroon.
AB  - PURPOSE: The aim of this study was to determine the prevalence and causes of
      bilateral and unilateral blindness in the town of Douala and its environs based
      on data from the ophthalmic unit of a tertiary hospital in Douala. METHODS: We
      conducted a retrospective epidemiological survey of consultations at the eye unit
      of the Douala General Hospital over the last 20 years (from January 1, 1990 to
      December 31, 2009). RESULTS: Out of the 1927 cases of blindness, 1000 were
      unilateral, corresponding to a hospital prevalence of 1.84% and 927 cases were
      bilateral, corresponding to a hospital prevalence of 1.71%. No statistically
      significant difference was noted between the two (P = 0.14). The leading causes
      of bilateral blindness were cataract (50.1%), glaucoma (19.7%), and diabetic
      retinopathy (7.8%) while the leading causes of unilateral blindness were cataract
      (40.4%), glaucoma (14.1%), and retinal detachment (9.1%). Cataract (51.2%),
      cortical blindness (16.3%), and congenital glaucoma (10%) were the leading causes
      of bilateral blindness in children aged less than 10 years. CONCLUSION: Blindness
      remains a public health problem in the Douala region with a hospital prevalence
      which is relatively higher than the national estimate given by the National
      Blindness Control Program.

PMID- 21966213
TI  - Successful mobilization of peripheral blood stem cells in children with cancer
      using plerixafor (Mozobil) and granulocyte-colony stimulating factor.
AB  - This paper describes the successful mobilization of peripheral blood stem cells
      for autologous transplantation in three children with malignant diseases by using
      plerixafor (Mozobil; Genzyme Corporation, Cambridge, MA) and granulocyte-colony
      stimulating factor (G-CSF) after failed previous mobilizations. A median sixfold
      increase in the number of circulating CD34+ cells after plerixafor treatment as
      compared with the baseline level was observed. An optimal CD34+ cell count for
      transplantation with one or two leukapheresis sessions was achieved. Mobilization
      using plerixafor was found to be safe with no adverse events. Therefore, the
      combination of G-CSF and plerixafor in children results in effective increases in
      peripheral CD34+ cell counts and reduces the risk of mobilization failure.

PMID- 21966212
TI  - Why has it been so difficult to prove the efficacy of alpha-1-antitrypsin
      replacement therapy? Insights from the study of disease pathogenesis.
AB  - Alpha-1-antitrypsin is the most abundant circulating protease inhibitor. It is
      mainly produced by the liver and secreted into the circulation where it acts to
      prevent excessive proteolytic damage in the lungs by the enzyme neutrophil
      elastase. The most common severe deficiency allele is the Z mutation, which
      causes the protein to self-associate into ordered polymers. These polymers
      accumulate within hepatocytes to cause liver damage. The resulting lack of
      circulating alpha(1)-antitrypsin predisposes the Z homozygote to proteolytic lung
      damage and emphysema. Other pathways may also contribute to the development of
      lung disease. In particular, polymers of Z alpha(1)-antitrypsin can form within
      the lung where they act as a pro-inflammatory stimulus that may exacerbate
      protease-mediated lung damage. Researchers recognized in the 1980s that plasma
      alpha(1)-antitrypsin levels could be restored by intravenous infusions of
      purified human protein. Alpha-1-antitrypsin replacement therapy was introduced in
      1987 but subsequent clinical trials have produced conflicting results, and to
      date there remains no widely accepted clinical evidence of the efficacy of
      alpha(1)-antitrypsin replacement therapy. This review addresses our current
      understanding of disease pathogenesis in alpha(1)-antitrypsin deficiency and
      questions why this treatment in isolation may not be effective. In particular it
      discusses the possible role of alpha(1)-antitrypsin polymers in exacerbating
      intrapulmonary inflammation and attenuating the efficacy of alpha(1)-antitrypsin
      replacement therapy.

PMID- 21966214
TI  - Emerging options in growth hormone therapy: an update.
AB  - Growth hormone (GH) was first used to treat a patient in 1958. For the next 25
      years it was available only from cadaver sources, which was of concern because of
      safety considerations and short supply. In 1985, GH produced by recombinant DNA
      techniques became available, expanding its possible uses. Since that time there
      have been three indications approved by the US Food and Drug Administration (FDA)
      for GH-deficiency states and nine indications approved for non-GH-deficiency
      states. In 2003 the FDA approved GH for use in idiopathic short stature (ISS),
      which may indirectly cover other diagnoses that have short stature as a feature.
      However, coverage for GH therapy is usually more reliably obtainable for a
      specific indication, rather than the ISS indication. Possible future uses for GH
      therapy could include the treatment of syndromes such as Russell-Silver syndrome
      or chondrodystrophy. Other non-short-stature indications could include wound
      healing and burns. Other uses that have been poorly studied include aging and
      physical performance, in spite of the interest already shown by elite athletes in
      using GH. The safety profile of GH developed over the past 25 years has shown it
      to be a very safe hormone with few adverse events associated with it. The
      challenge for the future is to follow these patients into adulthood to determine
      whether GH therapy poses any long-term risks.

PMID- 21966215
TI  - Association between vitamin D and pressure ulcers in older ambulatory adults:
      results of a matched case-control study.
AB  - BACKGROUND: Pressure ulcers are common among older adults, but knowledge about
      nutritional risk factors is still developing. Vitamin D deficiency is common in
      the elderly population and is required for normal skin proliferation. The role of
      vitamin D in pressure ulceration and wound healing is not known. The purpose of
      this case-control study was to determine the association between vitamin D levels
      and pressure ulceration in an older community-dwelling cohort. METHODS: All cases
      and controls were community-dwelling elderly older than 60 years in a primary
      care panel in Olmsted County, MN. Pressure ulcer cases were defined clinically.
      The controls were age-matched and gender-matched to controls without pressure
      ulceration. The main exposure variable was 25-hydroxyvitamin D levels in both
      groups. The other exposure variable was the Charlson Comorbidity Index used to
      measure medical comorbidity. The analysis included univariate and conditional
      logistic regression for 25-hydroxyvitamin D levels. RESULTS: The average
      (standard deviation) age of the study participants with a pressure ulcer was
      80.46 years (+/-8.67), and the average vitamin D level was 30.92 ng/mL (+/
      12.46). In univariate analysis, Vitamin D deficiency (levels < 25 ng/mL) was
      associated with pressure ulcers (odds ratio: 1.871, P = 0.0154). Comorbidities of
      the subjects calculated using the Charlson Comorbidity Index were also associated
      with pressure ulcers (odds ratio: 1.136, P < 0.001). In the final conditional
      logistical regression model, the association of Vitamin D and pressure ulcers
      became nonsignificant after adjustment for comorbid illness. CONCLUSION: Medical
      comorbidities increased the risk of pressure ulceration. Vitamin D deficiency was
      not an independent risk factor for pressure ulceration, and may be a marker of
      comorbid illness.

PMID- 21966216
TI  - Weight gain since menopause and its associations with weight loss maintenance in
      obese postmenopausal women.
AB  - OBJECTIVE: To examine the association between weight gain since menopause and
      weight regain after a weight loss program. METHODS: Participants were 19 obese
      women who participated in a 15-week weight loss program and a 12-month follow-up.
      Main outcomes were: body composition, resting metabolic rate, energy intake,
      energy expenditure, and weight regain at follow-up. RESULTS: All body composition
      measures significantly decreased after intervention (all P <= 0.01) while all
      measures of fatness increased significantly after the 12-month follow-up (P <=
      0.01). Body weight gain since menopause was associated with body weight regain (r
      = 0.65; P = 0.003) after follow-up even after adjustment for confounders.
      CONCLUSION: Weight gain since menopause is associated with body weight regain
      following the weight loss program. Therefore, weight gain since menopause should
      be considered as a factor influencing weight loss maintenance in older women.

PMID- 21966217
TI  - Minimally invasive treatment of lumbar spinal stenosis with a novel interspinous
      spacer.
AB  - PURPOSE: To assess the safety and effectiveness of a novel, minimally invasive
      interspinous spacer in patients with moderate lumbar spinal stenosis (LSS).
      METHODS: A total of 53 patients (mean age, 70 +/- 11 years; 45% female) with
      intermittent neurogenic claudication secondary to moderate LSS, confirmed on
      imaging studies, were treated with the Superion((r)) Interspinous Spacer
      (VertiFlex, Inc, San Clemente, CA) and returned for follow-up visits at 6 weeks,
      1 year, and 2 years. Study endpoints included axial and extremity pain severity
      with an 11-point numeric scale, Zurich Claudication Questionnaire (ZCQ), back
      function with the Oswestry Disability Index (ODI), health-related quality of life
      with the Physical Component Summary (PCS) and Mental Component Summary (MCS)
      scores from the SF-12, and adverse events. RESULTS: Axial and extremity pain each
      decreased 54% (both P < 0.001) over the 2-year follow-up period. ZCQ symptom
      severity scores improved 43% (P < 0.001) and ZCQ physical function improved 44%
      (P < 0.001) from pre-treatment to 2 years post-treatment. A statistically
      significant 50% improvement (P < 0.001) also was noted in back function. PCS and
      MCS each improved 40% (both P < 0.001) from pre-treatment to 2 years. Clinical
      success rates at 2 years were 83%-89% for ZCQ subscores, 75% for ODI, 78% for
      PCS, and 80% for MCS. No device infection, implant breakage, migration, or pull
      out was observed, although two (3.8%) patients underwent explant with subsequent
      laminectomy. CONCLUSION: Moderate LSS can be effectively treated with a minimally
      invasive interspinous spacer. This device is appropriate for select patients who
      have failed nonoperative treatment measures for LSS and meet strict anatomical
      criteria.

PMID- 21966218
TI  - The effect of the addition of resistance training to a dietary education
      intervention on apolipoproteins and diet quality in overweight and obese older
      adults.
AB  - OBJECTIVES: The aim of the study was to examine the additive effect of resistance
      training (RT) to a dietary education (DE) intervention on emerging coronary heart
      disease (CHD) risk factors, concentration of apolipoproteins B (apoB) and A-I
      (apoA-I), and Dietary Approaches to Stop Hypertension (DASH) Diet Index scores in
      overweight and obese older adults. PATIENTS AND METHODS: This was an ancillary
      study of a randomized clinical trial held in the Fall of 2008 at the University
      of Rhode Island. Participants were overweight or obese subjects (mean body mass
      index [BMI] of 31.7 kg/m(2)) randomized into two groups, one participating in DE
      only (n = 12) and the other participating in DE plus RT (DERT) (n = 15). The
      intervention involved all subjects participating in 30 minutes of DE per week for
      10 weeks. Subjects in the DERT group participated in an additional 40 minutes of
      RT three times per week for 10 weeks. Measurements taken were anthropometric
      (height, weight, waist circumference, and body composition using the BOD POD((r))
      [Body Composition System, v 2.14; Life Measurement Instruments, Concord, CA]),
      clinical (blood pressure), and biochemical (lipid profile and apoB and apoA-I
      concentrations), and the DASH Diet Index was used to measure diet quality.
      RESULTS: 27 subjects (11 males, 16 females), with a mean age of 66.6 +/- 4.3
      years, were included in analyses. The DERT subjects had significantly better
      triacylglycerol and apoB concentrations and DASH Diet Index scores than the DE
      subjects post-intervention. Improvements were seen within the DE group in energy
      intake, fat-free mass, and systolic blood pressure and within the DERT group in
      body weight, percentage of body fat, BMI, diastolic blood pressure, and oxidized
      low-density lipoprotein (all P < 0.05). CONCLUSION: The addition of RT
      effectively reduced CHD risk factors, body composition, and diet quality in
      overweight and obese older adults; DERT was more effective than DE alone in
      improving DASH Diet Index scores and lowering apoB concentrations but was not
      more effective in increasing apoA-I concentrations. Future research is needed to
      determine if apolipoproteins are superior to lipoprotein cholesterol
      concentrations in predicting CHD risk.

PMID- 21966220
TI  - Racial differences in tumor necrosis factor-alpha-induced endothelial
      microparticles and interleukin-6 production.
AB  - African Americans (AA) tend to have heightened systemic inflammation and
      endothelial dysfunction. Endothelial microparticles (EMP) are released from
      activated/apoptotic endothelial cells (EC) when stimulated by inflammation. The
      purpose of our study was to assess EMP responses to inflammatory cytokine (TNF
      alpha) and antioxidant (superoxide dismutase, SOD) conditions in human umbilical
      vein ECs (HUVECs) obtained from AA and Caucasians. EMPs were measured under four
      conditions: control (basal), TNF-alpha, SOD, and TNF-alpha + SOD. Culture
      supernatant was collected for EMP analysis by flow cytometry and IL-6 assay by
      ELISA. IL-6 protein expression was assessed by Western blot. AA HUVECs had
      greater EMP levels under the TNF-alpha condition compared to the Caucasian HUVECs
      (6.8 +/- 1.1 vs 4.7% +/- 0.4%, P = 0.04). The EMP level increased by 89% from
      basal levels in the AA HUVECs under the TNF-alpha condition (P = 0.01) compared
      to an 8% increase in the Caucasian HUVECs (P = 0.70). Compared to the EMP level
      under the TNF-alpha condition, the EMP level in the AA HUVECs was lower under the
      SOD only condition (2.9% +/- 0.3%, P = 0.005) and under the TNF-alpha + SOD
      condition (2.1% +/- 0.4%, P = 0.001). Basal IL-6 concentrations were 56.1 +/- 8.8
      pg/mL/MUg in the AA and 30.9 +/- 14.9 pg/mL/MUg in the Caucasian HUVECs (P =
      0.17), while basal IL-6 protein expression was significantly greater (P < 0.05)
      in the AA HUVECs. These preliminary observational results suggest that AA HUVECs
      may be more susceptible to the injurious effects of the proinflammatory cytokine,
      TNF-alpha.

PMID- 21966221
TI  - Superficial venous thrombosis: disease progression and evolving treatment
      approaches.
AB  - Treatment of superficial venous thrombosis (SVT) has recently shifted as
      increasing evidence suggests a higher than initially recognized rate of
      recurrence as well as concomitant deep venous thrombosis. Traditional therapies
      aimed at symptom control and disruption of the saphenofemoral junction are being
      called into question. The incidence of deep venous thrombosis has been reported
      to be 6%-40%, with symptomatic pulmonary embolism occurring in 2%-13% of
      patients. Asymptomatic pulmonary embolism is said to occur in up to one third of
      patients with SVT based on lung scans. The role of anticoagulation, including
      newer agents, is being elucidated, and surgical disruption of the saphenofemoral
      junction, while still an option for specific cases, is less frequently used as
      first-line treatment. The individual risk factors, including history of prior
      episodes of SVT, the presence of varicosities, and provoking factors including
      malignancy and hypercoagulable disorders, must all be considered to individualize
      the treatment plan. Given the potential morbidity of untreated SVT, prompt
      recognition and understanding of the pathophysiology and sequelae are paramount
      for clinicians treating patients with this disease. A personalized treatment plan
      must be devised for individual patients because the natural history varies by
      risk factor, presence or absence of DVT, and extent of involvement.

PMID- 21966219
TI  - Treating nausea and vomiting in palliative care: a review.
AB  - Nausea and vomiting are portrayed in the specialist palliative care literature as
      common and distressing symptoms affecting the majority of patients with advanced
      cancer and other life-limiting illnesses. However, recent surveys indicate that
      these symptoms may be less common and bothersome than has previously been
      reported. The standard palliative care approach to the assessment and treatment
      of nausea and vomiting is based on determining the cause and then relating this
      back to the "emetic pathway" before prescribing drugs such as dopamine
      antagonists, antihistamines, and anticholinergic agents which block
      neurotransmitters at different sites along the pathway. However, the evidence
      base for the effectiveness of this approach is meager, and may be in part because
      relevance of the neuropharmacology of the emetic pathway to palliative care
      patients is limited. Many palliative care patients are over the age of 65 years,
      making these agents difficult to use. Greater awareness of drug interactions and
      QT(c) prolongation are emerging concerns for all age groups. The selective
      serotonin receptor antagonists are the safest antiemetics, but are not used first
      line in many countries because there is very little scientific rationale or
      clinical evidence to support their use outside the licensed indications.
      Cannabinoids may have an increasing role. Advances in interventional
      gastroenterology are increasing the options for nonpharmacological management.
      Despite these emerging issues, the approach to nausea and vomiting developed
      within palliative medicine over the past 40 years remains relevant. It advocates
      careful clinical evaluation of the symptom and the person suffering it, and an
      understanding of the clinical pharmacology of medicines that are available for
      palliating them.

PMID- 21966222
TI  - Effect of melatonin on nocturnal blood pressure: meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: Patients with nocturnal hypertension are at higher risk for
      cardiovascular complications such as myocardial infarction and cerebrovascular
      insult. Published studies inconsistently reported decreases in nocturnal blood
      pressure with melatonin. METHODS: A meta-analysis of the efficacy and safety of
      exogenous melatonin in ameliorating nocturnal blood pressure was performed using
      a random effects model of all studies fitting the inclusion criteria, with
      subgroup analysis of fast-release versus controlled-release preparations.
      RESULTS: Seven trials (three of controlled-release and four of fast-release
      melatonin) with 221 participants were included. Meta-analysis of all seven
      studies did not reveal significant effects of melatonin versus placebo on
      nocturnal blood pressure. However, subgroup analysis revealed that controlled
      release melatonin significantly reduced nocturnal blood pressure whereas fast
      release melatonin had no effect. Systolic blood pressure decreased significantly
      with controlled-release melatonin (-6.1 mmHg; 95% confidence interval [CI] -10.7
      to -1.5; P = 0.009) but not fast-release melatonin (-0.3 mmHg; 95% CI -5.9 to
      5.30; P = 0.92). Diastolic blood pressure also decreased significantly with
      controlled-release melatonin (-3.5 mmHg; 95% CI -6.1 to -0.9; P = 0.009) but not
      fast-release melatonin (-0.2 mmHg; 95% CI -3.8 to 3.3; P = 0.89). No safety
      concerns were raised. CONCLUSION: Add-on controlled-release melatonin to
      antihypertensive therapy is effective and safe in ameliorating nocturnal
      hypertension, whereas fast-release melatonin is ineffective. It is necessary that
      larger trials of longer duration be conducted in order to determine the long-term
      beneficial effects of controlled-release melatonin in patients with nocturnal
      hypertension.

PMID- 21966223
TI  - Value of venous color flow duplex scan as initial screening test for geriatric
      inpatients with clinically suspected pulmonary embolism.
AB  - AIM: The contribution of lower extremity venous duplex scan to the diagnostic
      strategy for pulmonary embolism has been demonstrated by many authors. However,
      the positive diagnostic value of this noninvasive test in clinically suspected
      pulmonary embolism is not very high (10% - 18%). Since thromboembolic risks
      increase considerably in hospitalized patients with advanced age, this study aims
      to determine the importance of lower extremity venous color flow duplex scan in
      this particular subgroup of patients with clinically suspected pulmonary
      embolism. The effects of clinical presentation and risk factors on the results of
      duplex scan have been also studied. METHODS: Between July 2007 and January 2010,
      95 consecutive Lebanese geriatric (>= 60 years of age) inpatients with clinically
      suspected pulmonary embolism assessed in an academic tertiary-care center for
      complete lower extremity venous color flow duplex scan were retrospectively
      reviewed. Age varied between 60 and 96 years (mean, 79.9 years). Forty patients
      were males and 55 females. Absence of compressibility was the most important
      criteria for detecting acute venous thrombosis. RESULTS: Out of 95 patients, 33
      patients (34.7%) were diagnosed with recent deep venous thrombosis of lower
      extremities (14 proximal and 19 distal) using complete venous ultrasound. Nine of
      these 33 patients (27.2%) had a history of venous thromboembolism and eleven
      (33.3%) presented with edema of lower extremities. A total of 28 patients (84.8%)
      with positive duplex scan had associated risk factors for venous thromboembolism.
      CONCLUSION: Lower extremity venous color flow duplex scan appears to be a
      reasonable initial screening test in the diagnostic algorithm of pulmonary
      embolism in geriatric inpatients with clinically suspected pulmonary embolism.
      This is particularly true in patients with a history of venous thromboembolism,
      in patients with a clinical presentation suggesting venous thrombosis, in uremic
      patients and in patients with altered general and mental status who are not
      candidates for chest computed tomography.

PMID- 21966224
TI  - Signs for early diagnosis of heart failure in primary health care.
AB  - OBJECTIVE: The current guidelines for the diagnosis of heart failure (HF) are
      based on studies of hospital-based patients. The aim of this study is to describe
      the symptoms, clinical signs, and diagnostic procedures confirming the diagnosis
      of HF in primary health care. MATERIALS/SUBJECTS AND METHODS: Data were
      prospectively collected during a 2-year period by a nationwide network of
      sentinel practices. All adult patients without known HF, for which the diagnosis
      of HF was clinically suspected for the first time, were registered. When
      diagnosed, HF was confirmed after 1 month. RESULTS: 754 patients with a suspicion
      of HF were recorded. The diagnosis of HF was confirmed for 74% of the patients.
      The average age of the patients with confirmed HF was 77.7 years, and for those
      without HF 75.6 years (P = 0.018). From a logistic regression, breathlessness on
      exercise (P < 0.001), limitations of physical activity (P = 0.003), and orthopnea
      (P = 0.040) were the symptoms most associated with HF. The clinical signs most
      associated with HF, were pulmonary rales (P < 0.001), peripheral edema (P <
      0.001), and raised jugular venous pressure (P = 0.039). An electrocardiogram was
      performed in 75% of the cases, blood analyses in 68%, echocardiogram in 63%,
      chest X-ray in 61%, and determination of natriuretic peptides in 11% of the
      cases. CONCLUSION: Many clinical signs may occur in patients with HF. However,
      the occurrence of peripheral edema, breathlessness on exercise, or pulmonary
      rales, are highly suggestive for HF when diagnosed in primary health care, as is
      the case in hospital-admitted patients. The diagnosis of HF was often left
      unconfirmed by an echocardiogram and/or an electrocardiogram.

PMID- 21966225
TI  - Integrating psychoeducation in a basic computer skills course for people
      suffering from social anxiety: participants' experiences.
AB  - We describe a psychoeducational program integrated in a basic computer skills
      course for participants suffering from social anxiety. The two main aims of the
      course were: that the participants learn basic computer skills, and that the
      participants learn to cope better with social anxiety. Computer skills were
      taught by a qualified teacher. Psychoeducation and cognitive therapy skills,
      including topics such as anxiety coping, self-accept, and self-regulation, were
      taught by a clinical psychologist. Thirteen of 16 participants completed the
      course, which lasted 11 weeks. A qualitative analysis was performed, drawing on
      observations during the course and on interviews with the participants. The
      participants were positive about the integration of psychoeducation sessions in
      the computer course, and described positive outcomes for both elements, including
      improved computer skills, improved self-esteem, and reduced social anxiety. Most
      participants were motivated to undertake further occupational rehabilitation
      after the course.

PMID- 21966226
TI  - A randomized, comparative trial: does pillow type alter cervico-thoracic spinal
      posture when side lying?
AB  - BACKGROUND: Many patients ask for advice about choosing a pillow. This research
      was undertaken to determine if pillow type alters cervico-thoracic spine position
      when resting in the side-lying position. AIM: To investigate the effect of
      different pillow shape and content on the slope of cervico-thoracic spine
      segments when side lying. MATERIALS AND METHODS: The study was a randomized
      blinded comparative trial set in a laboratory that replicated a bedroom. The
      subjects were side sleepers aged over 18 years. Exclusion criteria were history
      of surgery to the cervico-thoracic spine, an injury or accident to the cervico
      thoracic spine in the preceding year, or currently receiving treatment for neck
      symptoms. Each participant rested in a standardized side-lying position for 10
      minutes on each of the trial pillows: regular shaped polyester, foam, feather,
      and latex pillows, and a contour shaped foam pillow. Reflective markers were
      placed on external occipital protuberance (EOP), C2, C4, C7, and T3, and digital
      images were recorded of subjects at 0 and 10 minutes on each pillow. Images were
      digitized using each reflective marker and the slope of each spinal segment
      calculated. Univariate analysis of variance models were used to investigate slope
      differences between pillows at 0 and 10 minutes. Significance was established at
      P < 0.01 to take account of chance effects from repeated measures and multiple
      comparisons. RESULTS: At 0 and 10 minutes, the EOP-C2, C2-C4, and C4-C7 segmental
      slopes were significantly different across all pillows. Significant differences
      were identified when comparing the feather pillow with the latex, regular and
      contour foam pillows, and when comparing the polyester and foam contour pillows.
      The regular and contour foam pillows produced similar slopes at all spinal
      segments. CONCLUSION: Cervico-thoracic spinal segment slope alters significantly
      when people change from a foam, latex, or polyester pillow to a feather pillow
      and vice versa. The shape of a foam pillow (contour versus regular shape) does
      not significantly alter cervico-thoracic spinal segment slope.

PMID- 21966227
TI  - Drug use and self-medication among children with respiratory illness or diarrhea
      in a rural district in Vietnam: a qualitative study.
AB  - AIMS: To explore the knowledge, attitudes, and behaviors of parents in their use
      of drugs for respiratory illness or diarrhea among children under 5 years of age,
      and to understand factors influencing self-medication. METHODS: A qualitative
      study was conducted, using in-depth interviews with two drug sellers and three
      health care providers, and four focus-group discussions with mothers of children
      under 5 years of age. Verbatim transcriptions were analyzed, and emerging themes
      and categories identified, using content analysis. RESULTS: Use of a number of
      different drugs was reported, including broad-spectrum antibiotics and
      corticosteroids. There was poor awareness of side-effects, antibiotic resistance,
      and drug efficacy. Factors influencing self-medication were perceptions of the
      illness in the child, waiting time, and convenience, the attitudes of public
      health medical staff, insufficient drug supply in public health facilities, and
      poor control of prescribed drugs on the market. CONCLUSION: Misuse and
      misconceptions regarding drug use gave rise to considerable problems. Mothers'
      knowledge and attitudes to illness and health care services played an important
      role in determining the nature of self-medication. Financial barriers were not
      the only obstacle to adequate treatment. Health services should be more
      accessible and responsive to the needs of the population.

PMID- 21966228
TI  - The burgeoning field of transdisciplinary adaptation research in Quebec (1998-):
      a climate change-related public health narrative.
AB  - This paper presents a public health narrative on Quebec's new climatic conditions
      and human health, and describes the transdisciplinary nature of the climate
      change adaptation research currently being adopted in Quebec, characterized by
      the three phases of problem identification, problem investigation, and problem
      transformation. A transdisciplinary approach is essential for dealing with
      complex ill-defined problems concerning human-environment interactions (for
      example, climate change), for allowing joint research, collective leadership,
      complex collaborations, and significant exchanges among scientists, decision
      makers, and knowledge users. Such an approach is widely supported in theory but
      has proved to be extremely difficult to implement in practice, and those who
      attempt it have met with heavy resistance, succeeding when they find the
      occasional opportunity within institutional or social contexts. In this paper we
      narrate the ongoing struggle involved in tackling the negative effects of climate
      change in multi-actor contexts at local and regional levels, a struggle that
      began in a quiet way in 1998. The paper will describe how public health
      adaptation research is supporting transdisciplinary action and implementation
      while also preparing for the future, and how this interaction to tackle a life
      world problem (adaptation of the Quebec public health sector to climate change)
      in multi-actors contexts has progressively been established during the last 13
      years. The first of the two sections introduces the social context of a Quebec
      undergoing climate changes. Current climatic conditions and expected changes will
      be described, and attendant health risks for the Quebec population. The second
      section addresses the scientific, institutional and normative dimensions of the
      problem. It corresponds to a "public health narrative" presented in three phases:
      (1) problem identification (1998-2002) beginning in northern Quebec; (2) problem
      investigation (2002-2006) in which the issues are successively explored,
      understood, and conceptualized for all of Quebec, and (3) problem transformation
      (2006-2009), which discusses major interactions among the stakeholders and the
      presentation of an Action Plan by a central actor, the Quebec government, in
      alliance with other stakeholders. In conclusion, we underline the importance, in
      the current context, of providing for a sustained transdisciplinary adaptation to
      climatic change. This paper should be helpful for (1) public health professionals
      confronted with establishing a transdisciplinary approach to a real-world problem
      other than climate change, (2) professionals in other sectors (such as public
      safety, built environment) confronted with climate change, who wish to implement
      transdisciplinary adaptive interventions and/or research, and (3) knowledge users
      (public and private actors; nongovernment organizations; citizens) from elsewhere
      in multi-contexts/environments/sectors who wish to promote complex collaborations
      (with us or not), collective leadership, and "transfrontier knowledge-to-action"
      for implementing climate change-related adaptation measures.

PMID- 21966231
TI  - Baby products and injuries in Canada: Is it still an issue?

PMID- 21966229
TI  - Clinical approach in treatment of resistant hypertension.
AB  - Resistant hypertension, defined as failure to achieve target blood pressure
      despite the use of optimal or maximum doses of at least 3 agents, one of which is
      a diuretic, or requiring 4 or more medications to achieve blood pressure goal, is
      likely to affect up to 20% of all patients with hypertension. Apparent resistant
      hypertension may be caused by medication nonadherence, substances that either
      interfere with antihypertensive mediations or cause blood pressure elevation, and
      under- or inappropriate medication treatment. Certain patient characteristics are
      associated with the presence of resistant hypertension and include chronic kidney
      disease, diabetes, obesity, and presence of end-organ damage (microalbuminuria,
      retinopathy, left-ventricular hypertrophy). Secondary causes of resistant
      hypertension are not uncommon and include obstructive sleep apnea, chronic kidney
      disease, primary aldosteronism, renal artery stenosis, pheochromocytoma, and
      Cushing's disease. Initial medication management usually includes adding or
      increasing the dose of a diuretic, which is effective in lowering the blood
      pressure of a large number of patients with resistant hypertension. Additional
      management options include maximizing lifestyle modification, combination therapy
      of antihypertensive agents depending on individual patient characteristics,
      adding less-commonly used fourth- or fifth-line antihypertensive agents, and
      referral to a hypertension specialist.

PMID- 21966230
TI  - Lipid Nanoparticles with Accessible Nickel as a Vaccine Delivery System for
      Single and Multiple His-tagged HIV Antigens.
AB  - Lipid-based nanoparticles (NPs) with a small amount of surface-chelated nickel
      (Ni-NPs) were developed to easily formulate the HIV his-tagged Tat protein, as
      well as to formulate and co-deliver two HIV antigens (his-p24 and his-Nef) on one
      particle. Female BALB/c mice were immunized by s.c. injection with his-Tat/Ni-NP
      formulation (1.5 MUg Tat-his/mouse) and control formulations on day 0 and 14. The
      day 28 anti-Tat specific IgG titer with his-Tat/Ni-NP was significantly greater
      than that with Alum/his-Tat. Furthermore, splenocytes from his-Tat/Ni-NP
      immunized mice secreted significantly higher IFN-gamma than those from mice
      immunized with Alum/his-Tat. Although Ni-NPs did not show better adjuvant
      activity than Tat-coated anionic NPs made with sodium dodecyl sulfate (SDS/NPs),
      they were less toxic than SDS/NPs. The initial results indicated that co
      immunization of mice using his-p24/his-Nef/Ni-NP induced greater antibody
      response compared to using Alum/his-p24/his-Nef. Co-delivery of two antigens
      using Ni-NPs also increased the immunogenicity of individual antigens compared to
      delivery of a single antigen by Ni-NPs. In conclusion, Ni-NPs are an efficient
      delivery system for HIV vaccines including both single antigen delivery and
      multiple antigen co-delivery.

PMID- 21966232
TI  - Prevalence of methicillin-resistant Staphylococcus aureus colonization in
      children and adolescents admitted to CHEO.

PMID- 21966233
TI  - Why perform a history and physical examination when we have magnetic resonance
      imaging?

PMID- 21966234
TI  - During influenza season, which children need an antiviral and which one should I
      prescribe? Do I need to verify that they have influenza first?

PMID- 21966235
TI  - The impact of an oral rehydration clinical pathway in a paediatric emergency
      department.
AB  - OBJECTIVE: To measure the impact of implementing an oral rehydration clinical
      pathway for children with mild to moderate dehydration from gastroenteritis in
      the paediatric emergency department (ED) on the indicators of health care
      utilization. METHODS: ED charts of children, six months to 17 years of age,
      meeting the criteria for the oral rehydration clinical pathway were reviewed.
      There were three 12-month periods of data collection: pre-implementation,
      transition and postimplementation. The clinical pathway consisted of a standard
      nursing assessment form and instructions on oral rehydration to be initiated and
      maintained by caregivers while waiting to see a physician. The primary outcome
      measure was ED length of visit (LOV) for children treated using the clinical
      pathway. This was compared with LOV for all other ED visits during the study
      periods to highlight the effect of the clinical pathway implementation. Secondary
      outcome measures included rate of intravenous rehydration, unscheduled return
      visits to the ED and hospital admission. RESULTS: During the three data
      collection periods, 11,816 children met the eligibility criteria. A decrease in
      the mean LOV of 24 min (95% CI 17 to 31) was observed, as well as a trivial
      decrease in the rate of intravenous rehydration therapy (14.6% to 12%) with
      implementation of the clinical pathway. CONCLUSION: The implementation of an oral
      rehydration clinical pathway in the ED led to a modest reduction in the ED LOV.

PMID- 21966236
TI  - The readability of paediatric patient information materials: Are families
      satisfied with our handouts and brochures?
AB  - OBJECTIVES: To determine the grade reading level of eight easily available
      patient handouts for parents of children with otitis media, to calculate the
      internal reliability and consistency of seven readability tests, and to explore
      the relationship between the grade reading level of a handout and parent
      satisfaction. METHODS: Eight patient handouts developed for the parents of
      children with otitis media were collected, stripped of all formatting and
      analyzed using seven different readability formulas. Cronbach's alpha and
      intraclass correlation coefficients (ICC) were calculated to determine the
      internal reliability and consistency of the seven formulas. Parents were surveyed
      on their satisfaction with three of the handouts, and their responses were
      compared with the handouts' reading grade levels using ANOVA. RESULTS: Only four
      of the eight handouts had a mean grade 8 or less reading level. None of the
      handouts had a grade 5 or less reading level. Cronbach's alpha was calculated to
      be 0.990, single measures ICC 0.931 and average class ICC 0.990, indicating
      extremely high internal reliability/consistency among the different readability
      tests. One-way ANOVA showed no evidence of a significant difference in parental
      satisfaction with the three handouts tested, despite their different grade
      reading levels (grades 7, 10 and 14) (P=0.24). CONCLUSIONS: While many
      readability formulas are available, the high internal reliability/consistency
      among them indicates that only one formula needs to be used to assess readability
      (eg, the Flesch-Kincaid Grade Level formula). Because there was no difference in
      parental satisfaction among three patient handouts that had widely different
      grade reading levels, studies should explore whether writing patient information
      materials explicitly to achieve low grade reading level scores is a worthwhile
      strategy.

PMID- 21966237
TI  - Congenital myotonic dystrophy in a national registry.
AB  - AIM: To describe the neonatal symptoms, developmental problems and chronic
      multisystem medical morbidities of congenital myotonic dystrophy (CDM) patients
      registered in the United States National Registry of Myotonic Dystrophy - a
      disease-specific, self-report program maintained since 2002. Comparisons with the
      Canadian Paediatric Surveillance Program for CDM are highlighted. METHODS:
      Genetically confirmed cases of CDM demonstrating symptoms in the first four weeks
      of life are described. Patients (or their caregivers) and physicians completed
      survey information at baseline and annually thereafter. RESULTS: Twenty-one
      patients were included (13 male and eight female), ranging from three to 24 years
      of age. The CTG trinucleotide repeat number ranged from 940 to 2100.
      Gastrointestinal, pneumonia and cardiac morbidities were most common. No deaths
      were noted. CONCLUSIONS: The United States Registry is a valuable resource for
      clinical research on patients with CDM; however, in contrast with the Canadian
      Paediatric Surveillance Program, some limitations are identified.

PMID- 21966238
TI  - Recommendations for the use of rotavirus vaccines in infants.
AB  - Rotavirus infection occurs in the majority of healthy children before five years
      of age, and is the most common diarrheal illness associated with hospitalization.
      The majority of children present with symptoms of vomiting, diarrhea and fever.
      As a result, rotavirus gastroenteritis is responsible for greater morbidity than
      other common childhood diarrheal illnesses. The highest risk of severe disease is
      in children younger than two years of age. It is estimated that one in 20
      children will require an emergency department visit. In addition to community
      acquired infections, hospital-acquired infections are also significant. There are
      currently two licensed rotavirus vaccines in Canada. Both vaccines are
      administered orally and are highly effective against severe disease and
      hospitalization. Large pre- and postmarketing studies have shown no increased
      risk of intussusception with the current rotavirus vaccines. The present
      statement provides information concerning the clinical disease and rotavirus
      vaccines in Canada.

PMID- 21966239
TI  - Tuberculosis in children: New diagnostic blood tests.
AB  - The interferon-gamma-release assays were developed to overcome the pitfalls and
      logistic difficulties of the tuberculin skin test (TST) for the diagnosis of
      latent tuberculosis infection (LTBI). These blood tests measure the in vitro
      production of interferon-gamma by sensitized lymphocytes in response to
      Mycobacterium tuberculosis-specific antigens. Two interferon-gamma-release assays
      are registered for use in Canada: the QuantiFERON-TB Gold In-Tube assay
      (Cellestis Inc, Australia) and the T.SPOT-TB test (Oxford Immunotec, United
      Kingdom). Evaluation of these tests has been hampered by the lack of a gold
      standard for LTBI, and limited paediatric data on their use. It appears that they
      are more specific than the TST, and may be useful for evaluating TST-positive
      patients at low risk of true LTBI. Moreover, they may add sensitivity if used in
      addition to the TST in immunocompromised patients, very young children and close
      contacts of infectious adults. A summary of these tests, their limitations and
      their application to clinical paediatric practice are described.

PMID- 21966240
TI  - Patterns of reporting by health care and nonhealth care professionals to child
      protection services in Canada.
AB  - BACKGROUND: All Canadian jurisdictions require certain professionals to report
      suspected or observed child maltreatment. The present study examined the types of
      maltreatment, level of harm and child functioning issues (controlling for family
      socioeconomic status, age and sex of the child) reported by health care and
      nonhealth care professionals. METHODS: chi(2) analyses and logistic regression
      were conducted on a national child welfare sample from the 2003 Canadian
      Incidence Study of Reported Child Abuse and Neglect (CIS-2003), and the
      differences in professional reporting were compared with its previous cycle (CIS
      1998) using Bonferroni-corrected CIs. RESULTS: Analysis of the CIS-2003 data
      revealed that the majority of substantiated child maltreatment was reported to
      service agencies by nonhealth care professionals (57%), followed by other
      informants (33%) and health care professionals (10%). The number of professional
      reports increased 2.5 times between CIS-1998 and CIS-2003, while nonprofessional
      reports increased 1.7 times. Of the total investigations, professional reports
      represented 59% in CIS-1998 and 67% in CIS-2003 (P<0.001). Compared with
      nonhealth care professionals, health care professionals more often reported
      younger children, children who experienced neglect and emotional maltreatment,
      and those assessed as suffering harm and child functioning issues, but less often
      reported exposure to domestic violence. CONCLUSION: The results indicate that
      health care professionals play an important role in identifying children in need
      of protection, considering harm and other child functioning issues. The authors
      discuss the reasons why under-reporting is likely to remain an issue.

PMID- 21966241
TI  - A Deployable In Vivo EPR Tooth Dosimeter for Triage After a Radiation Event
      Involving Large Populations.
AB  - In order to meet the potential need for emergency large-scale retrospective
      radiation biodosimetry following an accident or attack, we have developed
      instrumentation and methodology for in vivo electron paramagnetic resonance
      spectroscopy to quantify concentrations of radiation-induced radicals within
      intact teeth. This technique has several very desirable characteristics for
      triage, including independence from confounding biologic factors, a non-invasive
      measurement procedure, the capability to make measurements at any time after the
      event, suitability for use by non-expert operators at the site of an event, and
      the ability to provide immediate estimates of individual doses. Throughout
      development there has been a particular focus on the need for a deployable
      system, including instrumental requirements for transport and field use, the need
      for high throughput, and use by minimally trained operators.Numerous measurements
      have been performed using this system in clinical and other non-laboratory
      settings, including in vivo measurements with unexposed populations as well as
      patients undergoing radiation therapies. The collection and analyses of sets of
      three serially-acquired spectra with independent placements of the resonator, in
      a data collection process lasting approximately five minutes, provides dose
      estimates with standard errors of prediction of approximately 1 Gy. As an
      example, measurements were performed on incisor teeth of subjects who had either
      received no irradiation or 2 Gy total body irradiation for prior bone marrow
      transplantation; this exercise provided a direct and challenging test of our
      capability to identify subjects who would be in need of acute medical care.

PMID- 21966242
TI  - Kinetics of Hole Nucleation in Biomembrane Rupture.
AB  - The core component of a biological membrane is a fluid-lipid bilayer held
      together by interfacial-hydrophobic and van der Waals interactions, which are
      balanced for the most part by acyl chain entropy confinement. If biomembranes are
      subjected to persistent tensions, an unstable (nanoscale) hole will emerge at
      some time to cause rupture. Because of the large energy required to create a
      hole, thermal activation appears to be requisite for initiating a hole and the
      activation energy is expected to depend significantly on mechanical tension.
      Although models exist for the kinetic process of hole nucleation in tense
      membranes, studies of membrane survival have failed to cover the ranges of
      tension and lifetime needed to critically examine nucleation theory. Hence,
      rupturing giant (~20 MUm) membrane vesicles ultra-slowly to ultra-quickly with
      slow to fast ramps of tension, we demonstrate a method to directly quantify
      kinetic rates at which unstable holes form in fluid membranes, at the same time
      providing a range of kinetic rates from < 0.01 s(-1) to > 100 s(-1). Measuring
      lifetimes of many hundreds of vesicles, each tensed by precision control of
      micropipet suction, we have determined the rates of failure for vesicles made
      from several synthetic phospholipids plus 1:1 mixtures of phospho- and sphingo
      lipids with cholesterol, all of which represent prominent constituents of
      eukaryotic cell membranes. Plotted on a logarithmic scale, the failure rates for
      vesicles are found to rise dramatically with increase of tension. Converting the
      experimental profiles of kinetic rates into changes of activation energy versus
      tension, we show that the results closely match expressions for thermal
      activation derived from a combination of meso-scale theory and molecular-scale
      simulations of hole formation. Moreover, we demonstrate a generic approach to
      transform analytical fits of activation energies obtained from rupture
      experiments into energy landscapes characterizing the process hole nucleation
      along the reaction coordinate defined by hole size.

PMID- 21966243
TI  - Multiplexed Analysis of Peptide Functionality Using Lanthanide-based Structural
      Shift Reagents.
AB  - Functionally selective lanthanide-based ion mobility shift reagents are presented
      as a method to elucidate protein or peptide structural information as well as
      relative quantitation of protein expression profiles. Sequence information and
      site localization of primary amines (n-terminus and lysine), phosphorylation
      sites, and cysteine residues can be obtained in a data dependent manner using ion
      mobility-mass spectrometry (IM-MS). The high mass of the incorporated lanthanide
      ensures a significant shift of where the signal occurs in IM-MS conformation
      space. Peptide sequence information provided by the use of IM-MS shift reagents
      allows for both a more confident identification of peptides from complex mixtures
      and site localization following tandem MS experiments. Stable isotopes of the
      lanthanide series may also be used as relative quantitation labels since several
      lanthanides can be utilized in differential sample analyses.

PMID- 21966244
TI  - Deprotonated N-(2,4-Dinitrophenyl)amino Acids Undergo Cyclization in Solution and
      the Gas Phase.
AB  - The collisionally activated mass spectral fragmentations of N-(2,4
      dinitrophenyl)alanine and phenylalanine [M - H](-) may be gas-phase analogs of
      the base-catalyzed cyclization of N-(2,4-dinitrophenyl)amino acids in aqueous
      dioxane. This latter reaction is one source of the 2-substituted 5-nitro-1H
      benzimidazole-3-oxides, which are antibacterial agents. The fragmentation of both
      compounds, established by tandem mass spectrometric experiments and supported by
      molecular modeling using DFT methods, indicate that the [M - H](-) ions
      dissociate via sequential eliminations of CO(2) and H(2)O to produce deprotonated
      benzimidazole-N-oxide derivatives. The gas-phase cyclization reactions are
      analogous to the base-catalyzed cyclization in solution, except that in the
      latter case, the reactant must be a dianion for the reaction to occur on a
      reasonable time scale. The cyclization of N-(2-nitrophenyl)phenylalanine, which
      has one less nitro group, requires a stronger base for the cyclization than the
      compound with a second nitro group at the 4-position. Following losses of CO(2)
      and H(2)O are expulsions of both neutral molecules and free radicals, the latter
      being examples of violations of the even-electron ion rule.

PMID- 21966245
TI  - Genes coding industrially relevant enzymes in fungi: isolation and protein
      engineering of laccases.

PMID- 21966247
TI  - Evolution of multicopper oxidase genes in coprophilous and non-coprophilous
      members of the order sordariales.
AB  - Multicopper oxidases (MCO) catalyze the biological oxidation of various aromatic
      substrates and have been identified in plants, insects, bacteria, and wood
      rotting fungi. In nature, they are involved in biodegradation of biopolymers such
      as lignin and humic compounds, but have also been tested for various industrial
      applications. In fungi, MCOs have been shown to play important roles during their
      life cycles, such as in fruiting body formation, pigment formation and
      pathogenicity. Coprophilous fungi, which grow on the dung of herbivores, appear
      to encode an unexpectedly high number of enzymes capable of at least partly
      degrading lignin. This study compared the MCO-coding capacity of the coprophilous
      filamentous ascomycetes Podospora anserina and Sordaria macrospora with closely
      related non-coprophilous members of the order Sordariales. An increase of MCO
      genes in coprophilic members of the Sordariales most probably occurred by gene
      duplication and horizontal gene transfer events.

PMID- 21966246
TI  - Multiple multi-copper oxidase gene families in basidiomycetes - what for?
AB  - Genome analyses revealed in various basidiomycetes the existence of multiple
      genes for blue multi-copper oxidases (MCOs). Whole genomes are now available from
      saprotrophs, white rot and brown rot species, plant and animal pathogens and
      ectomycorrhizal species. Total numbers (from 1 to 17) and types of mco genes
      differ between analyzed species with no easy to recognize connection of gene
      distribution to fungal life styles. Types of mco genes might be present in one
      and absent in another fungus. Distinct types of genes have been multiplied at
      speciation in different organisms. Phylogenetic analysis defined different
      subfamilies of laccases sensu stricto (specific to Agaricomycetes), classical
      Fe2+-oxidizing Fet3-like ferroxidases, potential ferroxidases/laccases exhibiting
      either one or both of these enzymatic functions, enzymes clustering with pigment
      MCOs and putative ascorbate oxidases. Biochemically best described are laccases
      sensu stricto due to their proposed roles in degradation of wood, straw and plant
      litter and due to the large interest in these enzymes in biotechnology. However,
      biological functions of laccases and other MCOs are generally little addressed.
      Functions in substrate degradation, symbiontic and pathogenic intercations,
      development, pigmentation and copper homeostasis have been put forward. Evidences
      for biological functions are in most instances rather circumstantial by
      correlations of expression. Multiple factors impede research on biological
      functions such as difficulties of defining suitable biological systems for
      molecular research, the broad and overlapping substrate spectrum multi-copper
      oxidases usually possess, the low existent knowledge on their natural substrates,
      difficulties imposed by low expression or expression of multiple enzymes, and
      difficulties in expressing enzymes heterologously.

PMID- 21966248
TI  - Induction and transcriptional regulation of laccases in fungi.
AB  - Fungal laccases are phenol oxidases widely studied for their use in several
      industrial applications, including pulp bleaching in paper industry, dye
      decolourisation, detoxification of environmental pollutants and revalorization of
      wastes and wastewaters. The main difficulty in using these enzymes at industrial
      scale ensues from their production costs. Elucidation of the components and the
      mechanisms involved in regulation of laccase gene expression is crucial for
      increasing the productivity of native laccases in fungi. Laccase gene
      transcription is regulated by metal ions, various aromatic compounds related to
      lignin or lignin derivatives, nitrogen and carbon sources. In this manuscript,
      most of the published results on fungal laccase induction, as well as analyses of
      both the sequences and putative functions of laccase gene promoters are reviewed.
      Analyses of promoter sequences allow defining a correlation between the observed
      regulatory effects on laccase gene transcription and the presence of specific
      responsive elements, and postulating, in some cases, a mechanism for their
      functioning. Only few reports have investigated the molecular mechanisms
      underlying laccase regulation by different stimuli. The reported analyses suggest
      the existence of a complex picture of laccase regulation phenomena acting through
      a variety of cis acting elements. However, the general mechanisms for laccase
      transcriptional regulation are far from being unravelled yet.

PMID- 21966249
TI  - Directed evolution of fungal laccases.
AB  - Fungal laccases are generalists biocatalysts with potential applications that
      range from bioremediation to novel green processes. Fuelled by molecular oxygen,
      these enzymes can act on dozens of molecules of different chemical nature, and
      with the help of redox mediators, their spectrum of oxidizable substrates is
      further pushed towards xenobiotic compounds (pesticides, industrial dyes, PAHs),
      biopolymers (lignin, starch, cellulose) and other complex molecules. In recent
      years, extraordinary efforts have been made to engineer fungal laccases by
      directed evolution and semi-rational approaches to improve their functional
      expression or stability. All these studies have taken advantage of Saccharomyces
      cerevisiae as a heterologous host, not only to secrete the enzyme but also, to
      emulate the introduction of genetic diversity through in vivo DNA recombination.
      Here, we discuss all these endeavours to convert fungal laccases into valuable
      biomolecular platforms on which new functions can be tailored by directed
      evolution.

PMID- 21966250
TI  - Engineering laccases: in search for novel catalysts.
AB  - Laccases (p-diphenol oxidase, EC 1.10.3.2) are blue multicopper oxidases that
      catalyze the reduction of dioxygen to water, with a concomitant oxidation of
      small organic substrates. Since the description at the end of the nineteenth
      century of a factor catalyzing the rapid hardening of the latex of the Japanese
      lacquer trees (Rhus sp.) exposed to air laccases from different origins (plants,
      fungi bacteria) have been continuously discovered and extensively studied.
      Nowadays, molecular evolution and other powerful protein modification techniques
      offer possibilities to develop tailored laccases for a wide array of applications
      including drug synthesis, biosensors or biofuel cells. Here, we give an overview
      on strategies and results of our laboratory in the design of new biocatalysts
      based on laccases.

PMID- 21966251
TI  - Genetic and epigenetic signatures in human hepatocellular carcinoma: a systematic
      review.
AB  - Hepatocellular carcinoma (HCC) is the third most common cause of cancer deaths
      worldwide, and the incidence of this fatal disease is still on rise. The majority
      of HCCs emerge in the background of a chronic liver disease, such as chronic
      hepatitis and liver cirrhosis. The current understanding is that majority of HCCs
      evolve as a consequence of chronic inflammation and due to the presence of
      infection with hepatitis viruses. These underlying pathogenic stimuli
      subsequently induce a spectrum of genetic and epigenetic alterations in several
      cancer-related genes, which are involved in cell-cycle regulation, cell growth
      and adhesion. Such widespread genomic alterations cause disruption of normal
      cellular signaling and finally lead to the acquisition of a malignant phenotype
      in HCC. In general, the type of gene alterations, such as point mutations,
      deletion of chromosomal regions and abnormal methylation of gene promoters differ
      according to the individual targeted gene. In HCC, incidence of genetic
      alterations is relatively rare and is limited to a subset of few cancer-specific
      genes, such as the tumor suppressor p53, RB genes and oncogenes such as the
      CTNNB1. In contrast, epigenetic changes that involve aberrant methylation of
      genes and other post-transcriptional histone modifications occur far more
      frequently, and some of these epigenetic alterations are now being exploited for
      the development of molecular diagnostic signatures for HCC. In addition, recent
      findings of unique microRNA expression profiles also provide an evidence for the
      existence of novel mechanisms for gene expression regulation in HCC. In this
      review article, we will review the current state of knowledge on the activation
      of various oncogenic pathways and the inactivation of tumor suppressor pathways
      in HCC that result in the disruption of cancer-related gene function. In
      addition, we will specifically emphasize the clinical implication of some of
      these genetic and epigenetic alterations in the management of
      hepatocarcinogenesis.

PMID- 21966252
TI  - Genomic Diversity in Pig (Sus scrofa) and its Comparison with Human and other
      Livestock.
AB  - We have reviewed the current pig (Sus scrofa) genomic diversity within and
      between sites and compared them with human and other livestock. The current
      Porcine 60K single nucleotide polymorphism (SNP) panel has an average SNP
      distance in a range of 30 - 40 kb. Most of genetic variation was distributed
      within populations, and only a small proportion of them existed between
      populations. The average heterozygosity was lower in pig than in human and other
      livestock. Genetic inbreeding coefficient (F(IS)), population differentiation
      (F(ST)), and Nei's genetic distance between populations were much larger in pig
      than in human and other livestock. Higher average genetic distance existed
      between European and Asian populations than between European or between Asian
      populations. Asian breeds harboured much larger variability and higher average
      heterozygosity than European breeds. The samples of wild boar that have been
      analyzed displayed more extensive genetic variation than domestic breeds. The
      average linkage disequilibrium (LD) in improved pig breeds extended to 1 - 3 cM,
      much larger than that in human (~ 30 kb) and cattle (~ 100 kb), but smaller than
      that in sheep (~ 10 cM). European breeds showed greater LD that decayed more
      slowly than Asian breeds. We briefly discuss some processes for maintaining
      genomic diversity in pig, including migration, introgression, selection, and
      drift. We conclude that, due to the long time of domestication, the pig possesses
      lower heterozygosity, higher F(IS), and larger LD compared with human and cattle.
      This implies that a smaller effective population size and less informative
      markers are needed in pig for genome wide association studies.

PMID- 21966253
TI  - Recent Progress in Development of Tnt1 Functional Genomics Platform for Medicago
      truncatula and Lotus japonicus in Bulgaria.
AB  - Legumes, as protein-rich crops, are widely used for human food, animal feed and
      vegetable oil production. Over the past decade, two legume species, Medicago
      truncatula and Lotus japonicus, have been adopted as model legumes for genomics
      and physiological studies. The tobacco transposable element, Tnt1, is a powerful
      tool for insertional mutagenesis and gene inactivation in plants. A large
      collection of Tnt1-tagged lines of M. truncatula cv. Jemalong was generated
      during the course of the project 'GLIP': Grain Legumes Integrated Project, funded
      by the European Union (www.eugrainlegumes.org). In the project 'IFCOSMO':
      Integrated Functional and COmparative genomics Studies on the MOdel Legumes
      Medicago truncatula and Lotus japonicus, supported by a grant from the Ministry
      of Education, Youth and Science, Bulgaria, these lines are used for development
      of functional genomics platform of legumes in Bulgaria. This review presents
      recent advances in the evaluation of the M. truncatula Tnt1 mutant collection and
      outlines the steps that are taken in using the Tnt1-tagging for generation of a
      mutant collection of the second model legume L. japonicus. Both collections will
      provide a number of legume-specific mutants and serve as a resource for
      functional and comparative genomics research on legumes. Genomics technologies
      are expected to advance genetics and breeding of important legume crops (pea,
      faba bean, alfalfa and clover) in Bulgaria and worldwide.

PMID- 21966255
TI  - Fast synthesis of 1,3-DAG by Lecitase(r) Ultra-catalyzed esterification in
      solvent-free system.
AB  - Lecitase(r) Ultra, a phospholipase, was explored as an effective biocatalyst for
      direct esterification of glycerol with oleic acid to produce 1,3-DAG. Experiments
      were carried out in batch mode, and optimal reaction conditions were evaluated.
      In comparison with several organic solvent mediums, the solvent-free system was
      found to be more beneficial for this esterification reaction, which was further
      studied to investigate the reaction conditions including oleic acid/glycerol mole
      ratio, temperature, initial water content, enzyme load, and operating time. The
      results showed that Lecitase(r) Ultra catalyzed a fast synthesis of 1,3-DAG by
      direct esterification in a solvent-free medium. Under the optimal reaction
      conditions, a short reaction time 1.5 h was found to achieve the fatty acid
      esterification efficiency of 80.3 +/- 1.2% and 1,3-DAG content of 54.8 +/- 1.6
      wt% (lipid layer of reaction mixture mass). The reusability of Lecitase(r) Ultra
      was evaluated via recycling the excess glycerol layer in the reaction system. DAG
      in the upper lipid layer of reaction mixture was purified by molecular
      distillation and the 1,3-DAG-enriched oil with a purity of about 75 wt% was
      obtained.Practical applications: The new Lecitase(r) Ultra catalyzed process for
      production of 1,3-DAG from glycerol and oleic acid described in this study
      provides several advantages over conventional methods including short reaction
      time, the absence of a solvents and a high product yield.

PMID- 21966256
TI  - Analyses of in vitro nonenzymatic glycation of normal and variant hemoglobins by
      MALDI-TOF mass spectrometry.
AB  - MALDI-TOF mass spectrometry is used here to differentiate different glycoisoforms
      of normal and variant hemoglobins (Hbs) in nonenzymatic in vitro glycation.
      Single, double, and/or multiple glycation of the alpha-globin, beta-globin,
      and/or gamma-globin is observed. Different glycation rates are observed for
      various Hbs, and the normal Hb A has the slowest rate. Although the Hb A is
      relatively stable upon condensation with glucose at 37 degrees C, the variants Hb
      C, Hb E, Hb F, Hb Leiden, and Hb San Diego are less stable. In addition, data
      reveal that the number of glucose attached/Hb molecule (state of glycation)
      increases with longer incubation time, higher glucose concentration, and higher
      temperature. The pH dependence of the state of glycation is more complex and
      varies for different Hbs. Although pH has little effect on the state of glycation
      for Hb C, Hb E, and Hb Leiden, it increases for Hb A and Hb F upon changing the
      pH of the solution from phosphate buffer saline (pH 7.4) to carbonate buffer (pH
      10). Results obtained in this study could lead to the inference that the linkage
      of Hbs with glucose occurs in diabetic conditions in vivo (37 degrees C, ~neutral
      pH, ~0.007 M glucose), and the state of glycation is more severe in the
      individuals who carry abnormal Hbs.

PMID- 21966254
TI  - Regeneration of Hair Cells: Making Sense of All the Noise.
AB  - Hearing loss affects hundreds of millions of people worldwide by dampening or
      cutting off their auditory connection to the world. Current treatments for
      sensorineural hearing loss (SNHL) with cochlear implants are not perfect, leaving
      regenerative medicine as the logical avenue to a perfect cure. Multiple routes to
      regeneration of damaged hair cells have been proposed and are actively pursued.
      Each route not only requires a keen understanding of the molecular basis of ear
      development but also faces the practical limitations of stem cell regulation in
      the delicate inner ear where topology of cell distribution is essential.
      Improvements in our molecular understanding of the minimal essential genes
      necessary for hair cell formation and recent advances in stem cell manipulation,
      such as seen with inducible pluripotent stem cells (iPSCs) and epidermal neural
      crest stem cells (EPI-NCSCs), have opened new possibilities to advance research
      in translational stem cell therapies for individuals with hearing loss. Despite
      this, more detailed network maps of gene expression are needed, including an
      appreciation for the roles of microRNAs (miRs), key regulators of transcriptional
      gene networks. To harness the true potential of stem cells for hair cell
      regeneration, basic science and clinical medicine must work together to expedite
      the transition from bench to bedside by elucidating the full mechanisms of inner
      ear hair cell development, including a focus on the role of miRs, and adapting
      this knowledge safely and efficiently to stem cell technologies.

PMID- 21966257
TI  - Measurement of reactive oxygen species in the culture media using Acridan Lumigen
      PS-3 assay.
AB  - Reactive oxygen species (ROS) are generated continuously during aerobic
      metabolism. ROS are highly reactive molecules and in excessive amounts, can lead
      to protein and DNA oxidation, protein cross-linking, and cell death. Cell-culture
      models provide a valuable tool in understanding the mechanisms that lead to cell
      death. Accumulation of ROS within cells and/or their release into the culture
      media are highly cell type-specific. The ability to estimate ROS levels in the
      culture media is an important step in understanding the mechanisms contributing
      to disease processes. In this paper, we describe the optimization of a simple
      method to estimate ROS levels in the culture media using the Acridan Lumigen PS-3
      reagent provided in the Amersham ECL Plus kit (GE Healthcare, UK). We have shown
      that the Acridan Lumigen PS-3 assay generates ROS-specific chemiluminescence in
      fresh as well as media stored at -20 degrees C, in as little as 10-20 MUl of
      samples. The method was able to detect the dose (of stimulants)- and time (acute
      and chronic)-dependent changes in ROS levels in media collected from various cell
      types. Our results suggest that the kit reagents, PBS buffer, and various media
      did not contribute significantly to the overall chemiluminescence generated in
      the assay; however, we suggest that the unused medium specific for each cell type
      should be used as blanks and final readings of test samples normalized against
      these readings. As this method uses commonly available laboratory equipment and
      commercially available reagents, we believe this assay is convenient, economical,
      and specific in estimating ROS released extracellularly into the culture media.

PMID- 21966258
TI  - Quantifying histological features of cancer biospecimens for biobanking quality
      assurance using automated morphometric pattern recognition image analysis
      algorithms.
AB  - Biorepository-supported translational research depends on high-quality, well
      annotated specimens. Histopathology assessment contributes insight into how
      representative lesions are for research objectives. Feasibility of documenting
      histological proportions of tumor and stroma was studied in an effort to enhance
      information regarding biorepository tissue heterogeneity. Using commercially
      available software, unique spatial-spectral algorithms were developed for
      applying automated pattern recognition morphometric image analysis to quantify
      histologic tumor and nontumor tissue areas in biospecimen tissue sections.
      Measurements were acquired successfully for 75/75 (100%) lymphomas, 76/77 (98.7%)
      osteosarcomas, and 60/70 (85.7%) melanomas. The percentage of tissue area
      occupied by tumor varied among patients and tumor types and was distributed
      around medians of 94% [interquartile range (IQR)=14%] for lymphomas, 84% for
      melanomas (IQR=24%), and 39% for osteosarcomas (IQR=44%). Within-patient
      comparisons from a subset, including multiple individual patient specimens,
      revealed <=12% median coefficient of variation (CV) for lymphomas and melanomas.
      Phenotypic heterogeneity of osteosarcomas resulted in 33% median CV. Uniformly
      applied, tumor-specific pattern recognition software permits automated tissue
      feature quantification. Furthermore, dispersion analyses of area measurements
      across collections, as well as of multiple specimens from individual patients,
      support using limited tissue slices to gauge features for some tumor types.
      Quantitative image analysis automation is anticipated to minimize variability
      associated with routine biorepository pathologic evaluations and enhance
      biomarker discovery by helping to guide the selection of study-appropriate
      specimens.

PMID- 21966260
TI  - A Plea for Process in Personality Prevarication.
AB  - We make a series recommendations for focusing research on personality test
      faking. Overall we suggest that a focus on the response process test takers go
      through will accelerate our understanding of faking behavior. We argue that the
      decision making process for faking must be simple and dependent on a modest set
      of decision rules or heuristics. The set of heuristics used by any given test
      taker will, in turn, be the result of test taker goals and situational press. By
      focusing in on what the test taker is doing we will avoid adopting the wrong
      frame of reference and, hopefully, make ever more rapid progress.

PMID- 21966261
TI  - Filament depolymerization can explain chromosome pulling during bacterial
      mitosis.
AB  - Chromosome segregation is fundamental to all cells, but the force-generating
      mechanisms underlying chromosome translocation in bacteria remain mysterious.
      Caulobacter crescentus utilizes a depolymerization-driven process in which a ParA
      protein structure elongates from the new cell pole, binds to a ParB-decorated
      chromosome, and then retracts via disassembly, pulling the chromosome across the
      cell. This poses the question of how a depolymerizing structure can robustly pull
      the chromosome that disassembles it. We perform Brownian dynamics simulations
      with a simple, physically consistent model of the ParABS system. The simulations
      suggest that the mechanism of translocation is "self-diffusiophoretic": by
      disassembling ParA, ParB generates a ParA concentration gradient so that the ParA
      concentration is higher in front of the chromosome than behind it. Since the
      chromosome is attracted to ParA via ParB, it moves up the ParA gradient and
      across the cell. We find that translocation is most robust when ParB binds side
      on to ParA filaments. In this case, robust translocation occurs over a wide
      parameter range and is controlled by a single dimensionless quantity: the product
      of the rate of ParA disassembly and a characteristic relaxation time of the
      chromosome. This time scale measures the time it takes for the chromosome to
      recover its average shape after it is has been pulled. Our results suggest
      explanations for observed phenomena such as segregation failure, filament-length
      dependent translocation velocity, and chromosomal compaction.

PMID- 21966262
TI  - Neuromotor noise, error tolerance and velocity-dependent costs in skilled
      performance.
AB  - In motor tasks with redundancy neuromotor noise can lead to variations in
      execution while achieving relative invariance in the result. The present study
      examined whether humans find solutions that are tolerant to intrinsic noise.
      Using a throwing task in a virtual set-up where an infinite set of angle and
      velocity combinations at ball release yield throwing accuracy, our computational
      approach permitted quantitative predictions about solution strategies that are
      tolerant to noise. Based on a mathematical model of the task expected results
      were computed and provided predictions about error-tolerant strategies
      (Hypothesis 1). As strategies can take on a large range of velocities, a second
      hypothesis was that subjects select strategies that minimize velocity at release
      to avoid costs associated with signal- or velocity-dependent noise or higher
      energy demands (Hypothesis 2). Two experiments with different target
      constellations tested these two hypotheses. Results of Experiment 1 showed that
      subjects chose solutions with high error-tolerance, although these solutions also
      had relatively low velocity. These two benefits seemed to outweigh that for many
      subjects these solutions were close to a high-penalty area, i.e. they were risky.
      Experiment 2 dissociated the two hypotheses. Results showed that individuals were
      consistent with Hypothesis 1 although their solutions were distributed over a
      range of velocities. Additional analyses revealed that a velocity-dependent
      increase in variability was absent, probably due to the presence of a solution
      manifold that channeled variability in a task-specific manner. Hence, the general
      acceptance of signal-dependent noise may need some qualification. These findings
      have significance for the fundamental understanding of how the central nervous
      system deals with its inherent neuromotor noise.

PMID- 21966263
TI  - Network-based prediction and analysis of HIV dependency factors.
AB  - HIV Dependency Factors (HDFs) are a class of human proteins that are essential
      for HIV replication, but are not lethal to the host cell when silenced. Three
      previous genome-wide RNAi experiments identified HDF sets with little overlap. We
      combine data from these three studies with a human protein interaction network to
      predict new HDFs, using an intuitive algorithm called SinkSource and four other
      algorithms published in the literature. Our algorithm achieves high precision and
      recall upon cross validation, as do the other methods. A number of HDFs that we
      predict are known to interact with HIV proteins. They belong to multiple protein
      complexes and biological processes that are known to be manipulated by HIV. We
      also demonstrate that many predicted HDF genes show significantly different
      programs of expression in early response to SIV infection in two non-human
      primate species that differ in AIDS progression. Our results suggest that many
      HDFs are yet to be discovered and that they have potential value as prognostic
      markers to determine pathological outcome and the likelihood of AIDS development.
      More generally, if multiple genome-wide gene-level studies have been performed at
      independent labs to study the same biological system or phenomenon, our
      methodology is applicable to interpret these studies simultaneously in the
      context of molecular interaction networks and to ask if they reinforce or
      contradict each other.

PMID- 21966265
TI  - Signalling and the evolution of cooperative foraging in dynamic environments.
AB  - Understanding cooperation in animal social groups remains a significant challenge
      for evolutionary theory. Observed behaviours that benefit others but incur some
      cost appear incompatible with classical notions of natural selection; however,
      these behaviours may be explained by concepts such as inclusive fitness,
      reciprocity, intra-specific mutualism or manipulation. In this work, we examine a
      seemingly altruistic behaviour, the active recruitment of conspecifics to a food
      resource through signalling. Here collective, cooperative behaviour may provide
      highly nonlinear benefits to individuals, since group functionality has the
      potential to be far greater than the sum of the component parts, for example by
      enabling the effective tracking of a dynamic resource. We show that due to this
      effect, signalling to others is an evolutionarily stable strategy under certain
      environmental conditions, even when there is a cost associated to this behaviour.
      While exploitation is possible, in the limiting case of a sparse, ephemeral but
      locally abundant nutrient source, a given environmental profile will support a
      fixed number of signalling individuals. Through a quantitative analysis, this
      effective carrying capacity for cooperation is related to the characteristic
      length and time scales of the resource field.

PMID- 21966264
TI  - Network models of TEM beta-lactamase mutations coevolving under antibiotic
      selection show modular structure and anticipate evolutionary trajectories.
AB  - Understanding how novel functions evolve (genetic adaptation) is a critical goal
      of evolutionary biology. Among asexual organisms, genetic adaptation involves
      multiple mutations that frequently interact in a non-linear fashion (epistasis).
      Non-linear interactions pose a formidable challenge for the computational
      prediction of mutation effects. Here we use the recent evolution of beta
      lactamase under antibiotic selection as a model for genetic adaptation. We build
      a network of coevolving residues (possible functional interactions), in which
      nodes are mutant residue positions and links represent two positions found
      mutated together in the same sequence. Most often these pairs occur in the
      setting of more complex mutants. Focusing on extended-spectrum resistant
      sequences, we use network-theoretical tools to identify triple mutant
      trajectories of likely special significance for adaptation. We extrapolate
      evolutionary paths (n = 3) that increase resistance and that are longer than the
      units used to build the network (n = 2). These paths consist of a limited number
      of residue positions and are enriched for known triple mutant combinations that
      increase cefotaxime resistance. We find that the pairs of residues used to build
      the network frequently decrease resistance compared to their corresponding
      singlets. This is a surprising result, given that their coevolution suggests a
      selective advantage. Thus, beta-lactamase adaptation is highly epistatic. Our
      method can identify triplets that increase resistance despite the underlying
      rugged fitness landscape and has the unique ability to make predictions by
      placing each mutant residue position in its functional context. Our approach
      requires only sequence information, sufficient genetic diversity, and discrete
      selective pressures. Thus, it can be used to analyze recent evolutionary events,
      where coevolution analysis methods that use phylogeny or statistical coupling are
      not possible. Improving our ability to assess evolutionary trajectories will help
      predict the evolution of clinically relevant genes and aid in protein design.

PMID- 21966266
TI  - The next opportunity in anti-malaria drug discovery: the liver stage.

PMID- 21966267
TI  - APOBEC3A is a specific inhibitor of the early phases of HIV-1 infection in
      myeloid cells.
AB  - Myeloid cells play numerous roles in HIV-1 pathogenesis serving as a vehicle for
      viral spread and as a viral reservoir. Yet, cells of this lineage generally
      resist HIV-1 infection when compared to cells of other lineages, a phenomenon
      particularly acute during the early phases of infection. Here, we explore the
      role of APOBEC3A on these steps. APOBEC3A is a member of the APOBEC3 family that
      is highly expressed in myeloid cells, but so far lacks a known antiviral effect
      against retroviruses. Using ectopic expression of APOBEC3A in established cell
      lines and specific silencing in primary macrophages and dendritic cells, we
      demonstrate that the pool of APOBEC3A in target cells inhibits the early phases
      of HIV-1 infection and the spread of replication-competent R5-tropic HIV-1,
      specifically in cells of myeloid origins. In these cells, APOBEC3A affects the
      amount of vDNA synthesized over the course of infection. The susceptibility to
      the antiviral effect of APOBEC3A is conserved among primate lentiviruses,
      although the viral protein Vpx coded by members of the SIV(SM)/HIV-2 lineage
      provides partial protection from APOBEC3A during infection. Our results indicate
      that APOBEC3A is a previously unrecognized antiviral factor that targets primate
      lentiviruses specifically in myeloid cells and that acts during the early phases
      of infection directly in target cells. The findings presented here open up new
      venues on the role of APOBEC3A during HIV infection and pathogenesis, on the role
      of the cellular context in the regulation of the antiviral activities of members
      of the APOBEC3 family and more generally on the natural functions of APOBEC3A.

PMID- 21966268
TI  - Robust antigen specific th17 T cell response to group A Streptococcus is
      dependent on IL-6 and intranasal route of infection.
AB  - Group A streptococcus (GAS, Streptococcus pyogenes) is the cause of a variety of
      clinical conditions, ranging from pharyngitis to autoimmune disease. Peptide
      major histocompatibility complex class II (pMHCII) tetramers have recently
      emerged as a highly sensitive means to quantify pMHCII-specific CD4+ helper T
      cells and evaluate their contribution to both protective immunity and autoimmune
      complications induced by specific bacterial pathogens. In lieu of identifying an
      immunodominant peptide expressed by GAS, a surrogate peptide (2W) was fused to
      the highly expressed M1 protein on the surface of GAS to allow in-depth analysis
      of the CD4+ helper T cell response in C57BL/6 mice that express the I-A(b) MHCII
      molecule. Following intranasal inoculation with GAS-2W, antigen-experienced 2W:I
      A(b)-specific CD4+ T cells were identified in the nasal-associated lymphoid
      tissue (NALT) that produced IL-17A or IL-17A and IFN-gamma if infection was
      recurrent. The dominant Th17 response was also dependent on the intranasal route
      of inoculation; intravenous or subcutaneous inoculations produced primarily IFN
      gamma+ 2W:I-A(b+) CD4+ T cells. The acquisition of IL-17A production by 2W:I-A(b)
      specific T cells and the capacity of mice to survive infection depended on the
      innate cytokine IL-6. IL-6-deficient mice that survived infection became long
      term carriers despite the presence of abundant IFN-gamma-producing 2W:I-A(b)
      specific CD4+ T cells. Our results suggest that an imbalance between IL-17- and
      IFN-gamma-producing CD4+ T cells could contribute to GAS carriage in humans.

PMID- 21966269
TI  - Secretion of genome-free hepatitis B virus--single strand blocking model for
      virion morphogenesis of para-retrovirus.
AB  - As a para-retrovirus, hepatitis B virus (HBV) is an enveloped virus with a double
      stranded (DS) DNA genome that is replicated by reverse transcription of an RNA
      intermediate, the pregenomic RNA or pgRNA. HBV assembly begins with the formation
      of an "immature" nucleocapsid (NC) incorporating pgRNA, which is converted via
      reverse transcription within the maturing NC to the DS DNA genome. Only the
      mature, DS DNA-containing NCs are enveloped and secreted as virions whereas
      immature NCs containing RNA or single-stranded (SS) DNA are not enveloped. The
      current model for selective virion morphogenesis postulates that accumulation of
      DS DNA within the NC induces a "maturation signal" that, in turn, triggers its
      envelopment and secretion. However, we have found, by careful quantification of
      viral DNA and NCs in HBV virions secreted in vitro and in vivo, that the vast
      majority of HBV virions (over 90%) contained no DNA at all, indicating that NCs
      with no genome were enveloped and secreted as empty virions (i.e., enveloped NCs
      with no DNA). Furthermore, viral mutants bearing mutations precluding any DNA
      synthesis secreted exclusively empty virions. Thus, viral DNA synthesis is not
      required for HBV virion morphogenesis. On the other hand, NCs containing RNA or
      SS DNA were excluded from virion formation. The secretion of DS DNA-containing as
      well as empty virions on one hand, and the lack of secretion of virions
      containing single-stranded (SS) DNA or RNA on the other, prompted us to propose
      an alternative, "Single Strand Blocking" model to explain selective HBV
      morphogenesis whereby SS nucleic acid within the NC negatively regulates NC
      envelopment, which is relieved upon second strand DNA synthesis.

PMID- 21966270
TI  - Development of a transformation system for Chlamydia trachomatis: restoration of
      glycogen biosynthesis by acquisition of a plasmid shuttle vector.
AB  - Chlamydia trachomatis remains one of the few major human pathogens for which
      there is no transformation system. C. trachomatis has a unique obligate
      intracellular developmental cycle. The extracellular infectious elementary body
      (EB) is an infectious, electron-dense structure that, following host cell
      infection, differentiates into a non-infectious replicative form known as a
      reticulate body (RB). Host cells infected by C. trachomatis that are treated with
      penicillin are not lysed because this antibiotic prevents the maturation of RBs
      into EBs. Instead the RBs fail to divide although DNA replication continues. We
      have exploited these observations to develop a transformation protocol based on
      expression of beta-lactamase that utilizes rescue from the penicillin-induced
      phenotype. We constructed a vector which carries both the chlamydial endogenous
      plasmid and an E.coli plasmid origin of replication so that it can shuttle
      between these two bacterial recipients. The vector, when introduced into C.
      trachomatis L2 under selection conditions, cures the endogenous chlamydial
      plasmid. We have shown that foreign promoters operate in vivo in C. trachomatis
      and that active beta-lactamase and chloramphenicol acetyl transferase are
      expressed. To demonstrate the technology we have isolated chlamydial
      transformants that express the green fluorescent protein (GFP). As proof of
      principle, we have shown that manipulation of chlamydial biochemistry is possible
      by transformation of a plasmid-free C. trachomatis recipient strain. The
      acquisition of the plasmid restores the ability of the plasmid-free C.
      trachomatis to synthesise and accumulate glycogen within inclusions. These
      findings pave the way for a comprehensive genetic study on chlamydial gene
      function that has hitherto not been possible. Application of this technology
      avoids the use of therapeutic antibiotics and therefore the procedures do not
      require high level containment and will allow the analysis of genome function by
      complementation.

PMID- 21966271
TI  - Host phylogeny determines viral persistence and replication in novel hosts.
AB  - Pathogens switching to new hosts can result in the emergence of new infectious
      diseases, and determining which species are likely to be sources of such host
      shifts is essential to understanding disease threats to both humans and wildlife.
      However, the factors that determine whether a pathogen can infect a novel host
      are poorly understood. We have examined the ability of three host-specific RNA
      viruses (Drosophila sigma viruses from the family Rhabdoviridae) to persist and
      replicate in 51 different species of Drosophilidae. Using a novel analytical
      approach we found that the host phylogeny could explain most of the variation in
      viral replication and persistence between different host species. This effect is
      partly driven by viruses reaching a higher titre in those novel hosts most
      closely related to the original host. However, there is also a strong effect of
      host phylogeny that is independent of the distance from the original host, with
      viral titres being similar in groups of related hosts. Most of this effect could
      be explained by variation in general susceptibility to all three sigma viruses,
      as there is a strong phylogenetic correlation in the titres of the three viruses.
      These results suggest that the source of new emerging diseases may often be
      predictable from the host phylogeny, but that the effect may be more complex than
      simply causing most host shifts to occur between closely related hosts.

PMID- 21966272
TI  - A trigger enzyme in Mycoplasma pneumoniae: impact of the glycerophosphodiesterase
      GlpQ on virulence and gene expression.
AB  - Mycoplasma pneumoniae is a causative agent of atypical pneumonia. The formation
      of hydrogen peroxide, a product of glycerol metabolism, is essential for host
      cell cytotoxicity. Phosphatidylcholine is the major carbon source available on
      lung epithelia, and its utilization requires the cleavage of deacylated
      phospholipids to glycerol-3-phosphate and choline. M. pneumoniae possesses two
      potential glycerophosphodiesterases, MPN420 (GlpQ) and MPN566. In this work, the
      function of these proteins was analyzed by biochemical, genetic, and
      physiological studies. The results indicate that only GlpQ is an active
      glycerophosphodiesterase. MPN566 has no enzymatic activity as
      glycerophosphodiesterase and the inactivation of the gene did not result in any
      detectable phenotype. Inactivation of the glpQ gene resulted in reduced growth in
      medium with glucose as the carbon source, in loss of hydrogen peroxide production
      when phosphatidylcholine was present, and in a complete loss of cytotoxicity
      towards HeLa cells. All these phenotypes were reverted upon complementation of
      the mutant. Moreover, the glpQ mutant strain exhibited a reduced gliding
      velocity. A comparison of the proteomes of the wild type strain and the glpQ
      mutant revealed that this enzyme is also implicated in the control of gene
      expression. Several proteins were present in higher or lower amounts in the
      mutant. This apparent regulation by GlpQ is exerted at the level of transcription
      as determined by mRNA slot blot analyses. All genes subject to GlpQ-dependent
      control have a conserved potential cis-acting element upstream of the coding
      region. This element overlaps the promoter in the case of the genes that are
      repressed in a GlpQ-dependent manner and it is located upstream of the promoter
      for GlpQ-activated genes. We may suggest that GlpQ acts as a trigger enzyme that
      measures the availability of its product glycerol-3-phosphate and uses this
      information to differentially control gene expression.

PMID- 21966273
TI  - Expression of the RAE-1 family of stimulatory NK-cell ligands requires activation
      of the PI3K pathway during viral infection and transformation.
AB  - Natural killer (NK) cells are lymphocytes that play a major role in the
      elimination of virally-infected cells and tumor cells. NK cells recognize and
      target abnormal cells through activation of stimulatory receptors such as NKG2D.
      NKG2D ligands are self-proteins, which are absent or expressed at low levels on
      healthy cells but are induced upon cellular stress, transformation, or viral
      infection. The exact molecular mechanisms driving expression of these ligands
      remain poorly understood. Here we show that murine cytomegalovirus (MCMV)
      infection activates the phosphatidylinositol-3-kinase (PI3K) pathway and that
      this activation is required for the induction of the RAE-1 family of mouse NKG2D
      ligands. Among the multiple PI3K catalytic subunits, inhibition of the p110alpha
      catalytic subunit blocks this induction. Similarly, inhibition of p110alpha PI3K
      reduces cell surface expression of RAE-1 on transformed cells. Many viruses
      manipulate the PI3K pathway, and tumors frequently mutate the p110alpha oncogene.
      Thus, our findings suggest that dysregulation of the PI3K pathway is an important
      signal to induce expression of RAE-1, and this may represent a commonality among
      various types of cellular stresses that result in the induction of NKG2D ligands.

PMID- 21966274
TI  - Unconventional repertoire profile is imprinted during acute chikungunya infection
      for natural killer cells polarization toward cytotoxicity.
AB  - Chikungunya virus (CHIKV) is a worldwide emerging pathogen. In humans it causes a
      syndrome characterized by high fever, polyarthritis, and in some cases lethal
      encephalitis. Growing evidence indicates that the innate immune response plays a
      role in controlling CHIKV infection. We show here that CHIKV induces major but
      transient modifications in NK-cell phenotype and function soon after the onset of
      acute infection. We report a transient clonal expansion of NK cells that
      coexpress CD94/NKG2C and inhibitory receptors for HLA-C1 alleles and are
      correlated with the viral load. Functional tests reveal cytolytic capacity driven
      by NK cells in the absence of exogenous signals and severely impaired IFN-gamma
      production. Collectively these data provide insight into the role of this unique
      subset of NK cells in controlling CHIKV infection by subset-specific expansion in
      response to acute infection, followed by a contraction phase after viral
      clearance.

PMID- 21966277
TI  - Inference of relationships in population data using identity-by-descent and
      identity-by-state.
AB  - It is an assumption of large, population-based datasets that samples are
      annotated accurately whether they correspond to known relationships or unrelated
      individuals. These annotations are key for a broad range of genetics
      applications. While many methods are available to assess relatedness that involve
      estimates of identity-by-descent (IBD) and/or identity-by-state (IBS) allele
      sharing proportions, we developed a novel approach that estimates IBD0, 1, and 2
      based on observed IBS within windows. When combined with genome-wide IBS
      information, it provides an intuitive and practical graphical approach with the
      capacity to analyze datasets with thousands of samples without prior information
      about relatedness between individuals or haplotypes. We applied the method to a
      commonly used Human Variation Panel consisting of 400 nominally unrelated
      individuals. Surprisingly, we identified identical, parent-child, and full
      sibling relationships and reconstructed pedigrees. In two instances non-sibling
      pairs of individuals in these pedigrees had unexpected IBD2 levels, as well as
      multiple regions of homozygosity, implying inbreeding. This combined method
      allowed us to distinguish related individuals from those having atypical
      heterozygosity rates and determine which individuals were outliers with respect
      to their designated population. Additionally, it becomes increasingly difficult
      to identify distant relatedness using genome-wide IBS methods alone. However, our
      IBD method further identified distant relatedness between individuals within
      populations, supported by the presence of megabase-scale regions lacking IBS0
      across individual chromosomes. We benchmarked our approach against the hidden
      Markov model of a leading software package (PLINK), showing improved calling of
      distantly related individuals, and we validated it using a known pedigree from a
      clinical study. The application of this approach could improve genome-wide
      association, linkage, heterozygosity, and other population genomics studies that
      rely on SNP genotype data.

PMID- 21966276
TI  - Bacterial communities of diverse Drosophila species: ecological context of a host
      microbe model system.
AB  - Drosophila melanogaster is emerging as an important model of non-pathogenic host
      microbe interactions. The genetic and experimental tractability of Drosophila has
      led to significant gains in our understanding of animal-microbial symbiosis.
      However, the full implications of these results cannot be appreciated without the
      knowledge of the microbial communities associated with natural Drosophila
      populations. In particular, it is not clear whether laboratory cultures can serve
      as an accurate model of host-microbe interactions that occur in the wild, or
      those that have occurred over evolutionary time. To fill this gap, we
      characterized natural bacterial communities associated with 14 species of
      Drosophila and related genera collected from distant geographic locations. To
      represent the ecological diversity of Drosophilids, examined species included
      fruit-, flower-, mushroom-, and cactus-feeders. In parallel, wild host
      populations were compared to laboratory strains, and controlled experiments were
      performed to assess the importance of host species and diet in shaping bacterial
      microbiome composition. We find that Drosophilid flies have taxonomically
      restricted bacterial communities, with 85% of the natural bacterial microbiome
      composed of only four bacterial families. The dominant bacterial taxa are
      widespread and found in many different host species despite the taxonomic,
      ecological, and geographic diversity of their hosts. Both natural surveys and
      laboratory experiments indicate that host diet plays a major role in shaping the
      Drosophila bacterial microbiome. Despite this, the internal bacterial microbiome
      represents only a highly reduced subset of the external bacterial communities,
      suggesting that the host exercises some level of control over the bacteria that
      inhabit its digestive tract. Finally, we show that laboratory strains provide
      only a limited model of natural host-microbe interactions. Bacterial taxa used in
      experimental studies are rare or absent in wild Drosophila populations, while the
      most abundant associates of natural Drosophila populations are rare in the lab.

PMID- 21966278
TI  - Novel interactions between actin and the proteasome revealed by complex
      haploinsufficiency.
AB  - Saccharomyces cerevisiae has been a powerful model for uncovering the landscape
      of binary gene interactions through whole-genome screening. Complex heterozygous
      interactions are potentially important to human genetic disease as loss-of
      function alleles are common in human genomes. We have been using complex
      haploinsufficiency (CHI) screening with the actin gene to identify genes related
      to actin function and as a model to determine the prevalence of CHI interactions
      in eukaryotic genomes. Previous CHI screening between actin and null alleles for
      non-essential genes uncovered ~240 deleterious CHI interactions. In this report,
      we have extended CHI screening to null alleles for essential genes by mating a
      query strain to sporulations of heterozygous knock-out strains. Using an
      act1Delta query, knock-outs of 60 essential genes were found to be CHI with
      actin. Enriched in this collection were functional categories found in the
      previous screen against non-essential genes, including genes involved in
      cytoskeleton function and chaperone complexes that fold actin and tubulin. Novel
      to this screen was the identification of genes for components of the TFIID
      transcription complex and for the proteasome. We investigated a potential role
      for the proteasome in regulating the actin cytoskeleton and found that the
      proteasome physically associates with actin filaments in vitro and that some
      conditional mutations in proteasome genes have gross defects in actin
      organization. Whole-genome screening with actin as a query has confirmed that CHI
      interactions are important phenotypic drivers. Furthermore, CHI screening is
      another genetic tool to uncover novel functional connections. Here we report a
      previously unappreciated role for the proteasome in affecting actin organization
      and function.

PMID- 21966279
TI  - Essential roles of BCCIP in mouse embryonic development and structural stability
      of chromosomes.
AB  - BCCIP is a BRCA2- and CDKN1A(p21)-interacting protein that has been implicated in
      the maintenance of genomic integrity. To understand the in vivo functions of
      BCCIP, we generated a conditional BCCIP knockdown transgenic mouse model using
      Cre-LoxP mediated RNA interference. The BCCIP knockdown embryos displayed
      impaired cellular proliferation and apoptosis at day E7.5. Consistent with these
      results, the in vitro proliferation of blastocysts and mouse embryonic
      fibroblasts (MEFs) of BCCIP knockdown mice were impaired considerably. The BCCIP
      deficient mouse embryos die before E11.5 day. Deletion of the p53 gene could not
      rescue the embryonic lethality due to BCCIP deficiency, but partially rescues the
      growth delay of mouse embryonic fibroblasts in vitro. To further understand the
      cause of development and proliferation defects in BCCIP-deficient mice, MEFs were
      subjected to chromosome stability analysis. The BCCIP-deficient MEFs displayed
      significant spontaneous chromosome structural alterations associated with
      replication stress, including a 3.5-fold induction of chromatid breaks.
      Remarkably, the BCCIP-deficient MEFs had a ~20-fold increase in sister chromatid
      union (SCU), yet the induction of sister chromatid exchanges (SCE) was modestly
      at 1.5 fold. SCU is a unique type of chromatid aberration that may give rise to
      chromatin bridges between daughter nuclei in anaphase. In addition, the BCCIP
      deficient MEFs have reduced repair of irradiation-induced DNA damage and
      reductions of Rad51 protein and nuclear foci. Our data suggest a unique function
      of BCCIP, not only in repair of DNA damage, but also in resolving stalled
      replication forks and prevention of replication stress. In addition, BCCIP
      deficiency causes excessive spontaneous chromatin bridges via the formation of
      SCU, which can subsequently impair chromosome segregations in mitosis and cell
      division.

PMID- 21966280
TI  - The abnormal phenotypes of cartilage and bone in calcium-sensing receptor
      deficient mice are dependent on the actions of calcium, phosphorus, and PTH.
AB  - Patients with neonatal severe hyperparathyroidism (NSHPT) are homozygous for the
      calcium-sensing receptor (CaR) mutation and have very high circulating PTH,
      abundant parathyroid hyperplasia, and severe life-threatening hypercalcemia. Mice
      with homozygous deletion of CaR mimic the syndrome of NSHPT. To determine effects
      of CaR deficiency on skeletal development and interactions between CaR and
      1,25(OH)(2)D(3) or PTH on calcium and skeletal homeostasis, we compared the
      skeletal phenotypes of homozygous CaR-deficient (CaR(-/-)) mice to those of
      double homozygous CaR- and 1alpha(OH)ase-deficient [CaR(-/-)1alpha(OH)ase(-/-)]
      mice or those of double homozygous CaR- and PTH-deficient [CaR(-/-)PTH(-/-)] mice
      at 2 weeks of age. Compared to wild-type littermates, CaR(-/-) mice had
      hypercalcemia, hypophosphatemia, hyperparathyroidism, and severe skeletal growth
      retardation. Chondrocyte proliferation and PTHrP expression in growth plates were
      reduced significantly, whereas trabecular volume, osteoblast number, osteocalcin
      positive areas, expression of the ALP, type I collagen, osteocalcin genes, and
      serum ALP levels were increased significantly. Deletion of 1alpha(OH)ase in CaR(
      /-) mice resulted in a longer lifespan, normocalcemia, lower serum phosphorus,
      greater elevation in PTH, slight improvement in skeletal growth with increased
      chondrocyte proliferation and PTHrP expression, and further increases in indices
      of osteoblastic bone formation. Deletion of PTH in CaR(-/-) mice resulted in
      rescue of early lethality, normocalcemia, increased serum phosphorus,
      undetectable serum PTH, normalization in skeletal growth with normal chondrocyte
      proliferation and enhanced PTHrP expression, and dramatic decreases in indices of
      osteoblastic bone formation. Our results indicate that reductions in
      hypercalcemia play a critical role in preventing the early lethality of CaR(-/-)
      mice and that defects in endochondral bone formation in CaR(-/-) mice result from
      effects of the marked elevation in serum calcium concentration and the decreases
      in serum phosphorus concentration and skeletal PTHrP levels, whereas the
      increased osteoblastic bone formation results from direct effects of PTH.

PMID- 21966281
TI  - EAP Service Use in a Managed Behavioral Health Care Organization: From the
      Employee Perspective.
AB  - Contemporary employee assistance program (EAP) services are typically provided in
      broad-brush programs delivered by large external vendors in a network model. Yet
      research has not kept pace with EAP evolution, including in terms of how EAP
      clients themselves view services. We surveyed a random sample of EAP service
      users from a national provider (361 respondents). About one-third of respondents
      reported getting help for workplace issues. Most learned about the EAP through
      employer communications such as the company website. The large majority reported
      that the EAP helped them "a lot" or "some," suggesting they valued this benefit.

PMID- 21966282
TI  - Home C-ABPM for Preventive and Curative Health Care and Transdisciplinary
      Science.
AB  - The clinical everyday management of blood pressure (BP) and heart rate (HR) can
      be greatly improved by the mapping of time structures in home ambulatory BP and
      HR assessment. Thereby, we change focus from the BP and the HR to the dynamics of
      these variables. This change is achieved by computer-implemented chronomics, the
      mapping of chronomes, consisting of cyclicities (our concern herein) along with
      chaos and trends, in the service of cardiologists, general health care providers,
      the educated public, and transdisciplinary science. We here further illustrate
      the yield of chronomics in research on long BP and HR series covering years, some
      several decades long, and on archives of human sudden cardiac death revealing
      magnetoperiodisms, e.g., "years" longer than a calendar year, i.e., transyears.
      In this case of cardiac arrest, what we do not see, the 16- to 20-month transyear
      is prominent, in the absence of any signature of the calendar year, and so can be
      a cis-half-year of about 5 months.

PMID- 21966283
TI  - An examination of the epiphytic nature of Gambierdiscus toxicus, a dinoflagellate
      involved in ciguatera fish poisoning.
AB  - Twenty-four specimen of macroalgae were collected in nearshore waters of the
      island of Hawaii, identified, and maintained to examine how the epiphytic
      relationship between Gambierdiscus toxicus (isolate BIG12) varied among the
      macroalgal species. Gambierdiscus cells were introduced to petri dishes
      containing 100 g samples of each macroalgal host, which were examined at two, 16,
      24, and every 24 to 72 hours thereafter, over a 29-day period. Gambierdiscus
      proliferated in the presence of some host species (e.g., Galaxaura marginata and
      Jania sp.), but grew little in the presence of other species (e.g., Portieria
      hornemannii). Gambierdiscus exhibited high survival rates (>99%) in the presence
      of Chaetomorpha sp., but died before the end of the experiment (after 21 days)
      with other host species (e.g., Dictyota and Microdictyon spp.). Gambierdiscus
      avoided contact with Portieria hornemannii, but averaged up to 30% attachment
      with other host species. The numbers of Gambierdiscus cells belonging to one of
      three classes (alive and attached; alive and unattached; and dead) were
      determined for each time point. The 24 algal hosts were grouped according to
      their commonalities relative to these three classes using a Bray-Curtis
      similarity index, similarity profile (SIMPROF) permutation tests, and multi
      dimensional scaling (MDS) analysis (PRIMER 6). The resultant six groupings were
      used to construct different Gambierdiscus growth profiles for the different algal
      hosts. Group A is characterized by a preponderance of unattached cells and high
      mortality rates. Groups B, C, E, and F also displayed high proportions of
      unattached cells, but mortality either occurred later (Groups B and C) or rates
      were lower (Groups E and F). Group D had the highest proportion of attached
      cells. Group E contained three out of the four chlorophyte species, while Group F
      contained the majority of the rhodophytes. Over 50% of the species in Group F are
      considered to be palatable, whereas Groups A, B, and C are composed of species
      that exhibit chemical defenses against herbivory. The results of this study
      coupled with previous findings indicate that Gambierdiscus is not an obligate
      epiphyte; it can be free-swimming and found in the plankton. The conditions that
      lead to changes between epiphytic and planktonic stages need to be better studied
      in order to determine how they affect Gambierdiscus growth and physiology,
      connectivity and dispersion mechanisms, and toxin movement up into the foodweb.

PMID- 21966284
TI  - Synthesis and Biological Evaluation of Ezetimibe Analogs as Possible Cholesterol
      Absorption Inhibitors.
AB  - In order to investigate the SAR of Ezetimibe analogs for cholesterol absorption
      inhibitions, amide group and electron-deficient pyridine ring were introduced to
      the C-(3) carbon chain of Ezetimibe. Eight new derivatives of the 2-azetidinone
      cholesterol absorption inhibitors have been synthesized, and all of them were
      enantiomerically pure. All the new compounds were evaluated for their activity to
      inhibit cholesterol absorption in hamsters, and most of them showed comparable
      effects in lowering the levels of total cholesterol in the serum.

PMID- 21966275
TI  - Large-scale gene-centric analysis identifies novel variants for coronary artery
      disease.
AB  - Coronary artery disease (CAD) has a significant genetic contribution that is
      incompletely characterized. To complement genome-wide association (GWA) studies,
      we conducted a large and systematic candidate gene study of CAD susceptibility,
      including analysis of many uncommon and functional variants. We examined 49,094
      genetic variants in ~2,100 genes of cardiovascular relevance, using a customised
      gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733
      controls of European descent; 4,394 cases and 4,259 controls of South Asian
      origin). We attempted to replicate putative novel associations in an additional
      17,121 CAD cases and 40,473 controls. Potential mechanisms through which the
      novel variants could affect CAD risk were explored through association tests with
      vascular risk factors and gene expression. We confirmed associations of several
      previously known CAD susceptibility loci (eg, 9p21.3:p<10(-33); LPA:p<10(-19);
      1p13.3:p<10(-17)) as well as three recently discovered loci (COL4A1/COL4A2,
      ZC3HC1, CYP17A1:p<5*10(-7)). However, we found essentially null results for most
      previously suggested CAD candidate genes. In our replication study of 24
      promising common variants, we identified novel associations of variants in or
      near LIPA, IL5, TRIB1, and ABCG5/ABCG8, with per-allele odds ratios for CAD risk
      with each of the novel variants ranging from 1.06-1.09. Associations with
      variants at LIPA, TRIB1, and ABCG5/ABCG8 were supported by gene expression data
      or effects on lipid levels. Apart from the previously reported variants in LPA,
      none of the other ~4,500 low frequency and functional variants showed a strong
      effect. Associations in South Asians did not differ appreciably from those in
      Europeans, except for 9p21.3 (per-allele odds ratio: 1.14 versus 1.27
      respectively; P for heterogeneity = 0.003). This large-scale gene-centric
      analysis has identified several novel genes for CAD that relate to diverse
      biochemical and cellular functions and clarified the literature with regard to
      many previously suggested genes.

PMID- 21966285
TI  - Effective drift and diffusion of a particle jumping between mobile and immobile
      states.
AB  - We study propagation of a particle that jumps between two states, in which it
      moves with different velocities and diffusion coefficients. To simplify analysis,
      in the main part of the paper we derive formulas assuming that in one of the
      states the particle is immobile. A generalization to the case when the particle
      is mobile in both states is given at the end of the paper. The formulas show how
      the effective drift velocity and effective diffusion coefficient depend on jump
      rates between the two states as well as on the particle velocities and diffusion
      coefficients in these states. Specifically, we find that the effective diffusion
      coefficient can exhibit a non-monotonic behavior as a function of the ratio of
      the jump rates.

PMID- 21966286
TI  - Management of progressive genu varum in a patient with Dyggve-Melchior-Clausen
      syndrome.
AB  - We describe the orthopaedic management of progressive genu varum in a child who
      manifested the full phenotypic characterization of Dyggve-Melchior-Clausen
      syndrome.

PMID- 21966287
TI  - Efficacy of dose-reduced lenalidomide in patients with refractory or recurrent
      multiple myeloma.
AB  - PURPOSE: Introduction of lenalidomide has expanded the therapeutic options for
      refractory and recurrent multiple myeloma (MM) patients. However, the application
      of the approved doses may be difficult in some patients due to adverse effects.
      EXPERIMENTAL DESIGN: Therefore, we evaluated the efficacy and safety of
      lenalidomide in 10 patients with relapsed and refractory MM who received a
      reduced dose due to leukopenia (4), polyneuropathy (1), muscle cramps (1),
      thrombocytopenia (1), renal insufficiency (1), at the request of patient (1), as
      continuous therapy (1), either from the beginning (2) or during treatment (8).
      They received lenalidomide at a mean (median) daily dose of 14 (15) mg/d once a
      day (days 1-21 every 28 days) in combination with dexamethasone at a mean
      (median) dose of 17.6 (28) mg per day (4-40 mg) on days 1-4, 9-12 and 17-20.
      RESULTS: Mean (median) duration of treatment with lenalidomide was 15.1 (15)
      months. Partial response or better was reported in seven and minimal response or
      better was reported in eight patients. Mean (median) values for time-to
      progression (TTP) and for progression-free survival (PFS) were 8.7 (4) months.
      Mean overall survival (OS) has not been reached, all patients are still alive.
      CONCLUSION: In conclusion, dose-reduced lenalidomide is an effective and well
      tolerated treatment for patients with recurrent or refractory MM who cannot
      tolerate full doses.

PMID- 21966288
TI  - Biplane double-supported screw fixation (F-technique): a method of screw fixation
      at osteoporotic fractures of the femoral neck.
AB  - The present work introduces a method of screw fixation of femoral neck fractures
      in the presence of osteoporosis, according to an original concept of the
      establishment of two supporting points for the implants and their biplane
      positioning in the femoral neck and head. The provision of two steady supporting
      points for the implants and the highly increased (obtuse) angle at which they are
      positioned allow the body weight to be transferred successfully from the head
      fragment onto the diaphysis, thanks to the strength of the screws, with the
      patient's bone quality being of least importance. The position of the screws
      allows them to slide under stress with a minimal risk of displacement. The method
      was developed in search of a solution for those patients for whom primary
      arthroplasty is contraindicated. The method has been analysed in relation to
      biomechanics and statics. For the first time, a new function is applied to a
      screw fixation-the implant is presented as a simple beam with an overhanging end.

PMID- 21966289
TI  - Landmark optimization using local curvature for point-based nonlinear rodent
      brain image registration.
AB  - Purpose. To develop a technique to automate landmark selection for point-based
      interpolating transformations for nonlinear medical image registration. Materials
      and Methods. Interpolating transformations were calculated from homologous point
      landmarks on the source (image to be transformed) and target (reference image).
      Point landmarks are placed at regular intervals on contours of anatomical
      features, and their positions are optimized along the contour surface by a
      function composed of curvature similarity and displacements of the homologous
      landmarks. The method was evaluated in two cases (n = 5 each). In one, MRI was
      registered to histological sections; in the second, geometric distortions in EPI
      MRI were corrected. Normalized mutual information and target registration error
      were calculated to compare the registration accuracy of the automatically and
      manually generated landmarks. Results. Statistical analyses demonstrated
      significant improvement (P < 0.05) in registration accuracy by landmark
      optimization in most data sets and trends towards improvement (P < 0.1) in others
      as compared to manual landmark selection.

PMID- 21966290
TI  - A growth curve model with fractional polynomials for analysing incomplete time
      course data in microarray gene expression studies.
AB  - Identifying the various gene expression response patterns is a challenging issue
      in expression microarray time-course experiments. Due to heterogeneity in the
      regulatory reaction among thousands of genes tested, it is impossible to manually
      characterize a parametric form for each of the time-course pattern in a gene by
      gene manner. We introduce a growth curve model with fractional polynomials to
      automatically capture the various time-dependent expression patterns and
      meanwhile efficiently handle missing values due to incomplete observations. For
      each gene, our procedure compares the performances among fractional polynomial
      models with power terms from a set of fixed values that offer a wide range of
      curve shapes and suggests a best fitting model. After a limited simulation study,
      the model has been applied to our human in vivo irritated epidermis data with
      missing observations to investigate time-dependent transcriptional responses to a
      chemical irritant. Our method was able to identify the various nonlinear time
      course expression trajectories. The integration of growth curves with fractional
      polynomials provides a flexible way to model different time-course patterns
      together with model selection and significant gene identification strategies that
      can be applied in microarray-based time-course gene expression experiments with
      missing observations.

PMID- 21966291
TI  - Toxicity of Methylated Bismuth Compounds Produced by Intestinal Microorganisms to
      Bacteroides thetaiotaomicron, a Member of the Physiological Intestinal
      Microbiota.
AB  - Methanoarchaea have an outstanding capability to methylate numerous metal(loid)s
      therefore producing toxic and highly mobile derivatives. Here, we report that the
      production of methylated bismuth species by the methanoarchaeum
      Methanobrevibacter smithii, a common member of the human intestine, impairs the
      growth of members of the beneficial intestinal microbiota at low concentrations.
      The bacterium Bacteroides thetaiotaomicron, which is of great importance for the
      welfare of the host due to its versatile digestive abilities and its protective
      function for the intestine, is highly sensitive against methylated, but not
      against inorganic, bismuth species. The level of methylated bismuth species
      produced by the methanoarchaeum M. smithii in a coculture experiment causes a
      reduction of the maximum cell density of B. thetaiotaomicron. This observation
      suggests that the production of methylated organometal(loid) species in the human
      intestine, caused by the activity of methanoarchaea, may affect the health of the
      host. The impact of the species to reduce the number of the physiological
      intestinal microbiota brings an additional focus on the potentially harmful role
      of methanoarchaea in the intestine of a higher organism.

PMID- 21966292
TI  - Adjuvant Use of Ivabradine in Acute Heart Failure due to Myocarditis.
AB  - We report two cases of young men in whom acute heart failure due to myocarditis
      was diagnosed. The patients had been transferred to the intensive care unit (ICU)
      with commencing symptoms of acute heart failure and consecutive multiorgan
      failure for further treatment and to evaluate the indication for implantation of
      a ventricular assist device or for high urgent orthotopic heart transplantation.
      In both patients, the I(f)-channel inhibitor ivabradine was administered off
      label to provide selective heart rate reduction, and thus support hemodynamic
      stabilization. Though currently considered off-label use in patients suffering
      from severe hypotension and acute heart failure, the use of ivabradine may
      beneficially influence outcome by allowing optimization of the patient's heart
      rate concomitant to initial measures of clinical stabilization.

PMID- 21966293
TI  - Massive pulmonary thromboembolism and stroke.
AB  - A 38-year-old HIV-positive female, recently started on antiretroviral therapy,
      presented in extremis. She had features suggestive of an HIV-associated
      cardiomyopathy complicated by the following problems: a four-day-old stroke,
      extensive deep venous thrombosis, and massive pulmonary embolism. She received
      intravenous streptokinase with rapid improvement, both haemodynamically and,
      unexpectedly, neurologically. Our case illustrates that a positive outcome is
      potentially possible where the two conditions coincide.

PMID- 21966294
TI  - An overview of brain-derived neurotrophic factor and implications for excitotoxic
      vulnerability in the hippocampus.
AB  - The present paper examines the nature and function of brain-derived neurotrophic
      factor (BDNF) in the hippocampal formation and the consequences of changes in its
      expression. The paper focuses on literature describing the role of BDNF in
      hippocampal development and neuroplasticity. BDNF expression is highly sensitive
      to developmental and environmental factors, and increased BDNF signaling enhances
      neurogenesis, neurite sprouting, electrophysiological activity, and other
      processes reflective of a general enhancement of hippocampal function. Such
      increases in activity may mediate beneficial effects such as enhanced learning
      and memory. However, the increased activity also comes at a cost: BDNF plasticity
      renders the hippocampus more vulnerable to hyperexcitability and/or excitotoxic
      damage. Exercise dramatically increases hippocampal BDNF levels and produces
      behavioral effects consistent with this phenomenon. In analyzing the literature
      regarding exercise-induced regulation of BDNF, this paper provides a theoretical
      model for how the potentially deleterious consequences of BDNF plasticity may be
      modulated by other endogenous factors. The peptide galanin may play such a role
      by regulating hippocampal excitability.

PMID- 21966296
TI  - Testing for the existence of clusters.
AB  - Detecting and determining clusters present in a certain sample has been an
      important concern, among researchers from different fields, for a long time. In
      particular, assessing whether the clusters are statistically significant, is a
      question that has been asked by a number of experimenters. Recently, this
      question arose again in a study in maize genetics, where determining the
      significance of clusters is crucial as a primary step in the identification of a
      genome-wide collection of mutants that may affect the kernel composition.Although
      several efforts have been made in this direction, not much has been done with the
      aim of developing an actual hypothesis test in order to assess the significance
      of clusters. In this paper, we propose a new methodology that allows the
      examination of the hypothesis test H(0) : kappa=1 vs. H(1) : kappa=k, where kappa
      denotes the number of clusters present in a certain population. Our procedure,
      based on Bayesian tools, permits us to obtain closed form expressions for the
      posterior probabilities corresponding to the null hypothesis. From here, we
      calibrate our results by estimating the frequentist null distribution of the
      posterior probabilities in order to obtain the p-values associated with the
      observed posterior probabilities. In most cases, actual evaluation of the
      posterior probabilities is computationally intensive and several algorithms have
      been discussed in the literature. Here, we propose a simple estimation procedure,
      based on MCMC techniques, that permits an efficient and easily implementable
      evaluation of the test. Finally, we present simulation studies that support our
      conclusions, and we apply our method to the analysis of NIR spectroscopy data
      coming from the genetic study that motivated this work.

PMID- 21966295
TI  - Immunopathology and immunogenetics of allergic bronchopulmonary aspergillosis.
AB  - Allergic bronchopulmonary aspergillosis (ABPA) is a Th2 hypersensitivity lung
      disease in response to Aspergillus fumigatus that affects asthmatic and cystic
      fibrosis (CF) patients. Sensitization to A. fumigatus is common in both atopic
      asthmatic and CF patients, yet only 1%-2% of asthmatic and 7%-9% of CF patients
      develop ABPA. ABPA is characterized by wheezing and pulmonary infiltrates which
      may lead to pulmonary fibrosis and/or bronchiectasis. The inflammatory response
      is characterized by Th2 responses to Aspergillus allergens, increased serum IgE,
      and eosinophilia. A number of genetic risks have recently been identified in the
      development of ABPA. These include HLA-DR and HLA-DQ, IL-4 receptor alpha chain
      (IL-4RA) polymorphisms, IL-10 -1082GA promoter polymorphisms, surfactant protein
      A2 (SP-A2) polymorphisms, and cystic fibrosis transmembrane conductance regulator
      gene (CFTR) mutations. The studies indicate that ABPA patients are genetically at
      risk to develop skewed and heightened Th2 responses to A. fumigatus antigens.
      These genetic risk studies and their consequences of elevated biologic markers
      may aid in identifying asthmatic and CF patients who are at risk to the
      development of ABPA. Furthermore, these studies suggest that immune modulation
      with medications such as anti-IgE, anti-IL-4, and/or IL-13 monoclonal antibodies
      may be helpful in the treatment of ABPA.

PMID- 21966297
TI  - Efficacy and safety of human placental extract solution on fatigue: a double
      blind, randomized, placebo-controlled study.
AB  - Introduction. Fatigue is a common symptom, but only a few effective treatments
      are available. This study was conducted to assess the efficacy and safety of the
      human placental extract solution, which has been known to have a fatigue recovery
      effect. Methods. A total of 315 subjects were randomly assigned to three groups:
      group 1 (with Unicenta solution administration), group 2 (with exclusively human
      placental extract administration, excluding other ingredients from the Unicenta
      solution), and the placebo group. Subsequently, solutions were administered for
      four weeks. Results. The fatigue recovery rate was 71.00% in group 1, 71.72% in
      group 2, and 44.21% in the placebo group, which show statistically significant
      differences between the group 1 and the placebo group (P value = 0.0002), and
      between group 2 and the placebo group (P value = 0.0001). Conclusion. The human
      placental extract solution was effective in the improvement of fatigue.

PMID- 21966298
TI  - Comparison of effects of the ethanolic extracts of brazilian propolis on human
      leukemic cells as assessed with the MTT assay.
AB  - Propolis is a resinous product collected by honey bees. It was also reported that
      propolis has a wide variety of biological actions, including antimicrobial
      activity and antioxidant, anti-inflammatory, and suppressive effects of dioxin
      toxicity activities. The aim of this study was to compare the in vitro cytotoxic
      activities of green propolis (G12) and red propolis (G13) in human leukemia
      cells. These cells were incubated with different concentrations of propolis and
      48 hours after the IC(50) was calculated for each cell. The results showed that
      the red propolis has cytotoxic effect in vitro higher than green propolis. Red
      propolis was showed to be cytostatic in K562 cells and caused the same amount of
      apoptosis as its control Gleevec. In conclusion, these results showed that red
      propolis is more cytotoxic than the green propolis in a variety of human cell
      lines of leukemia. Red propolis may contain drugs capable of inhibiting cancer
      cell growth. Therefore, further isolation of respective chemical ingredients from
      the red propolis (G13) for identification of the activities is necessary.

PMID- 21966299
TI  - Demographic Disequilibrium in Early Twentieth Century Thailand: Falling
      Mortality, Rising Fertility, or Both?
AB  - Estimates of Thai crude birth and death rates date from 1920 when the former was
      around 20 per thousand higher than the latter, implying natural increase of 2
      percent per annum. Such disequilibrium cannot have been the norm over the long
      term historical past, when population growth must have been comparatively slow.
      This paper explores the bases for likely past relative equilibrium between
      Siamese birth and death rates, then seeks to explain the disequilibrium apparent
      by 1920. Classic demographic transition theory postulates initially high birth
      and death rates, this equilibrium eventually being broken by falling mortality.
      In Thailand, however, there is likely to have been both significant mortality
      decline and appreciable fertility increase after 1850, as the virtual elimination
      of indigenous warfare, rapid growth of the export rice economy and the demise of
      slavery and corvee labour created a new domestic environment. Characterized by
      more dispersed, often frontier, settlement, this environment was unprecedentedly
      sedate and settled, afforded ordinary households a previously unknown level of
      control over their resources of labour, and generated optimism about prospects
      for the next generation.

PMID- 21966300
TI  - Plasma volume expansion resulting from intravenous glucose tolerance test.
AB  - OBJECTIVE: To quantify the degree of plasma volume expansion that occurs during
      an intravenous glucose tolerance test (IVGTT). METHODS: Twenty healthy volunteers
      (mean age, 28 years) underwent IVGTTs in which 0.3 g/kg of glucose 30% was
      injected as a bolus over 1 min. Twelve blood samples were collected over 75 min.
      The plasma glucose and blood hemoglobin concentrations were used to calculate the
      volume distribution (V(d)) and the clearance (CL) of both the exogenous glucose
      and the injected fluid volume. RESULTS: The IVGTT caused a virtually instant
      plasma volume expansion of 10%. The half-life of the glucose averaged 15 min and
      the plasma volume expansion 16 min. Correction of the fluid kinetic model for
      osmotic effects after injection reduced CL for the infused volume by 85%, which
      illustrates the strength of osmosis in allocating fluid back to the intracellular
      fluid space. Simulations indicated that plasma volume expansion can be reduced to
      60% by increasing the injection time from 1 to 5 min and reducing the glucose
      load from 0.3 to 0.2 g/kg. CONCLUSION: A regular IVGTT induced an acute plasma
      volume expansion that peaked at 10% despite the fact that only 50-80 mL of fluid
      were administered.

PMID- 21966301
TI  - Individual health services.
AB  - BACKGROUND: The German statutory health insurance (GKV) reimburses all health
      care services that are deemed sufficient, appropriate, and efficient. According
      to the German Medical Association (BAK), individual health services (IGeL) are
      services that are not under liability of the GKV, medically necessary or
      recommendable or at least justifiable. They have to be explicitly requested by
      the patient and have to be paid out of pocket. RESEARCH QUESTIONS: The following
      questions regarding IGeL in the outpatient health care of GKV insurants are
      addressed in the present report: What is the empirical evidence regarding offers,
      utilization, practice, acceptance, and the relation between physician and
      patient, as well as the economic relevance of IGeL?What ethical, social, and
      legal aspects are related to IGeL? FOR TWO OF THE MOST COMMON IGEL, THE SCREENING
      FOR GLAUCOMA AND THE SCREENING FOR OVARIAN AND ENDOMETRIAL CANCER BY VAGINAL
      ULTRASOUND (VUS), THE FOLLOWING QUESTIONS ARE ADDRESSED: What is the evidence for
      the clinical effectiveness?Are there sub-populations for whom screening might be
      beneficial? METHODS: The evaluation is divided into two parts. For the first part
      a systematic literature review of primary studies and publications concerning
      ethical, social and legal aspects is performed. In the second part, rapid
      assessments of the clinical effectiveness for the two examples, glaucoma and VUS
      screening, are prepared. Therefore, in a first step, HTA-reports and systematic
      reviews are searched, followed by a search for original studies published after
      the end of the research period of the most recent HTA-report included. RESULTS:
      29 studies were included for the first question. Between 19 and 53% of GKV
      members receive IGeL offers, of which three-quarters are realised. 16 to 19% of
      the insurants ask actively for IGeL. Intraocular tension measurement is the most
      common single IGeL service, accounting for up to 40% of the offers. It is
      followed by ultrasound assessments with up to 25% of the offers. Cancer screening
      and blood or laboratory services are also frequent and represent a major
      proportion of the demand. The ethical, social, and legal aspects discussed in the
      context of IGeL concern eight subject areas: autonomous patient decisions versus
      obtrusion,commercialization of medicine, duty of patient information, benefit,
      evidence, and (quality) control, role and relation of physicians and
      patients,relation to the GKV, social inequality,formally correct performance. For
      glaucoma screening, no randomized controlled trial (RCT) is identified that shows
      a patient relevant benefit. For VUS three RCT are included. However, they do not
      yet present mortality data concerning screened and non-screened persons. VUS
      screening shows a high degree of over-diagnosis in turn leading to invasive
      interventions. To diagnose one invasive carcinoma, 30 to 35 surgical procedures
      are necessary. CONCLUSION: IGeL are a relevant factor in the German statutory
      health care system. To provide more transparency, the requests for evidence-based
      and independent patient information should be considered. Whether official
      positive and negative-lists could be an appropriate instrument to give guidance
      to patients and physicians, should be examined. Generally, IGeL must be seen in
      the broader context of the discussions about the future design and development of
      the German health care system.

PMID- 21966302
TI  - Expandable endoprosthesis for limb-sparing surgery in children: long-term
      results.
AB  - PURPOSE: Most children today with bone sarcomas undergo limb-sparing surgery.
      When treating children younger than 12 years of age, the result is significant
      limb length discrepancy (LLD). One of the solutions is the use of an expandable
      endoprosthesis. METHODS: A retrospective analysis of 38 skeletally immature
      patients with bone sarcoma of the lower limb in whom different types of
      expandable endoprostheses were used from January 1988 to December 2005 were
      included. All patients were under the age of 14 years. There were 26 osteosarcoma
      and 12 Ewing's sarcomas. The data collected included the tumor characteristics,
      the surgical and other treatment modalities, complications and their treatment,
      and the final LLD and functional results. RESULTS: Fifty-five percent of the
      patients survived and had a mean follow-up of 113 months. All survivors reached
      skeletal maturity at the time of last follow-up. Seventy-one percent of the
      survivors had satisfactory function and 29% had a poor result. There were three
      secondary amputations due to local recurrence. Complications were documented in
      58% of patients; the most common was infection that was diagnosed 56 times
      (primary 16% and secondary 84%). A significant correlation was found between
      function and final LLD (greater than 5 cm = inferior function), the number of
      complications, and the number of surgical procedures performed other than
      prosthesis elongation. The younger the patient was at definitive surgery, the
      shorter the time it took for the prosthesis to fail. CONCLUSION: In order to
      improve results, the number of operations must be reduced. This can be achieved
      by the use of novel non-invasive expandable endoprostheses or biological
      reconstruction.

PMID- 21966303
TI  - Meningococcal purpura fulminans in children: I. Initial orthopedic management.
AB  - BACKGROUND: Purpura fulminans is a rare and extremely severe infection, mostly
      due to Neisseria meningitidis frequently causing early orthopedic lesions. Few
      studies have reported on the initial surgical management of acute purpura
      fulminans. The aim of this study is to look at the predictive factors in
      orthopedic outcome in light of the initial surgical management in children
      surviving initial resuscitation. METHODS: Nineteen patients referred to our
      institution between 1987 and 2005 were taken care of at the very beginning of the
      purpura fulminans. All cases were retrospectively reviewed so as to collect
      information on the total skin necrosis, vascular insufficiency, gangrene, and
      total duration of vasopressive treatment. RESULTS: All patients had multiorgan
      failure; only one never developed any skin necrosis or ischemia. Eighteen
      patients lost tissue, leading to 22 skin grafts, including two total skin grafts.
      There was only one graft failure. Thirteen patients were concerned by an
      amputation, representing, in total, 54 fingers, 36 toes, two transmetatarsal, and
      ten transtibial below-knee amputations, with a mean delay of 4 weeks after onset
      of the disease. Necrosis seems to affect mainly the lower limbs, but there is no
      predictive factor that impacted on the orthopedic outcome. We did not perform any
      fasciotomy or compartment pressure measurement to avoid non-perfusion worsening;
      nonetheless, our outcome in this series is comparable to existing series in the
      literature. V.A.C.((r)) therapy could be promising regarding the management of
      skin necrosis in this particular context. While suffering from general multiorgan
      failure, great care should be observed not to miss any additional osseous or
      articular infection, as some patients also develop local osteitis and
      osteomyelitis that are often not diagnosed. CONCLUSIONS: We do not advocate very
      early surgery during the acute phase of purpura fulminans, as it does not change
      the orthopedic outcome in these children. By performing amputations and skin
      coverage some time after the acute phase, we obtained similar results to those
      found in the literature.

PMID- 21966304
TI  - Meningococcal purpura fulminans in children. II: Late orthopedic sequelae
      management.
AB  - BACKGROUND: Purpura fulminans is a rare and extremely severe infection, mostly
      due to Neisseria meningitidis. Nineteen patients were followed up immediately
      after the initial multivisceral failure in order to diagnose late-onset
      orthopedic sequelae. We report our experience with these 19 patients, in light of
      our medical follow-up protocol and surgical management. MATERIALS AND METHODS:
      Nineteen patients were referred for acute purpura fulminans between 1987 and 2005
      to our institution and followed up prospectively until the present. We collected
      information on all diagnosed orthopedic sequelae, all surgical procedures
      performed, and the actual orthopedic outcome. RESULTS: Fourteen patients
      developed at least one orthopedic sequel after a mean of 2 years delay, with a
      mean of 8.65 years follow-up (range 3-22 years). The most common presentation was
      lower limb physeal growth plate arrest in eight patients involving 18 growth
      plates, leading to five limb length discrepancies and 12 significant knee and/or
      ankle deviations. Patients were treated by completing epiphysiodesis in addition
      to limb lengthening and/or reaxation osteotomies, except for two patients, in
      which epiphysiolysis was performed. All outcomes are, to date, satisfactory, with
      both knee and ankle axes within the physiological range. Among the seven patients
      who underwent below-knee amputation, six needed stump revision because of skin
      conflict (4) or prosthetics misadaptation due to upper tibial varus (2).
      Regarding the upper limb, three patients presented with four cicatricial scar
      bands, one located on a ring finger, two at the first commissure, and one at the
      wrist (all were successfully treated by enlargement Z-plasties). Two patients
      developed hip avascular necrosis. CONCLUSION: It is important for children
      diagnosed with meningococcal purpura fulminans to be followed up closely starting
      from the very beginning by a pediatric orthopedic surgeon. It ensures that late
      onset orthopedic sequelae will be diagnosed early. In accordance to the
      literature, this study highlights the high rate of lower limb epiphysiodesis,
      above all other types of sequelae. This study reports a possible link between
      purpura fulminans and avascular necrosis of the hip.

PMID- 21966305
TI  - Donor site morbidity following the harvesting of cortical bone graft from the
      tibia in children.
AB  - INTRODUCTION: Since the nature of complications following the harvesting of bone
      from the tibia in children is not well documented in the literature, we undertook
      this study in order to determine the frequency and nature of donor site
      complications following the harvesting of large cortical strut grafts from the
      tibial diaphysis in children. MATERIALS AND METHODS: During the past 19 years,
      tibial cortical grafts were harvested from 47 children on 77 separate occasions,
      mainly for the treatment of congenital pseudarthrosis of the tibia. The technique
      of graft harvesting was identical in every case. Case records of these 47
      children were reviewed. Forty of these children were reviewed at a mean period of
      5.5 years. RESULTS: No immediate post-operative complications were noted and, at
      follow-up, apart from mild bowing of the anterior cortex of the tibia, no
      deformities were encountered. The tibial cortex reformed completely and this
      facilitated repeat graft harvesting when required. The only major complication
      was a stress fracture of the tibia in one boy. CONCLUSION: Harvesting cortical
      bone graft from the tibia is simple and is fraught with negligible morbidity.

PMID- 21966306
TI  - Fixation of subtrochanteric extending/derotational femoral osteotomies with the
      Locking Compression Plate in ambulatory neuro-orthopaedic patients.
AB  - PURPOSE: Patients with neuro-orthopaedic disorders often develop hip flexion
      contractures or rotational hip deformities. Increasing deformities impair the
      already diminished walking abilities and proximal femoral osteotomies are often
      performed to maintain/improve walking abilities. Fixation of the osteotomies with
      condylar plates has been successfully used but does often not allow immediate
      postoperative full weight bearing. To avoid a substantial postoperative
      rehabilitation deficit and additional bone loss due to inactivity, a
      postoperative treatment with full weight bearing is, therefore, wishful. Newer
      fixed-angled implants with stronger anchoring in osteopenic bone might fit these
      demands. The objective of this study was to evaluate bone healing and the
      complication rate after proximal extending and/or derotational femoral osteotomy
      fixed with 3.5/4.5 Locking Compression Plate (LCP; Synthes((r))) and
      postoperative full weight bearing in ambulatory neuro-orthopaedic patients.
      METHODS: Fifteen ambulatory neuro-orthopaedic patients (12 cerebral palsy [CP], 1
      trisomy 21, 2 hemiparesis) with a mean age of 13.7 years (range 7-22) with hip
      flexion contractures and/or rotational deformities underwent subtrochanteric (n =
      26) osteotomy between July 2004 and October 2007. All patients were allowed to
      bear their full weight postoperatively. We investigated the fusion rate, implant
      failure, and general complication rate until union had occurred. RESULTS:
      Fourteen patients (mean weight 42.0 kg [range 21.8-59]) uneventfully achieved
      solid fusion. One patient (19 years of age, 73 kg) needed revision surgery due to
      implant failure with consecutive varus deformity and achieved solid fusion after
      the second intervention. Besides one superficial wound infection, no other
      complications occurred. CONCLUSIONS: Subtrochanteric extending and/or
      derotational osteotomies fixed with an LCP are a reliable procedure in neuro
      orthopaedic patients. Most patients can be treated with early postoperative full
      weight bearing. However, in heavier patients, possible implant failure must be
      considered.

PMID- 21966307
TI  - Contoured iliac crest allograft interposition for pericapsular acetabuloplasty in
      developmental dislocation of the hip: technique and short-term results.
AB  - BACKGROUND: Pericapsular acetabuloplasty procedures have been widely used as an
      integral component of combined surgery to treat developmental hip dislocation
      after walking age. The stability of the acetabuloplasty and the maintenance of
      the acetabular correction will depend on the structural integrity of the iliac
      crest autograft, which, traditionally, has been inserted as the interposition
      material. Problems related to the use of an autograft have been encountered by
      various surgeons-including the authors-namely, graft displacement and resorption,
      which may necessitate internal fixation or result in revision surgery. To
      overcome autograft failure, the use of an allograft as the interposition material
      has been introduced by some surgeons. This study describes the radiologic results
      of 147 hips treated for developmental hip dislocation by means of a standard
      protocol of open hip reduction and pericapsular acetabuloplasty with a contoured
      iliac crest allograft as the interposition material. METHODS: This retrospective
      study reviewed the radiographs of 147 hips presenting with late developmental
      dislocation which were treated by open reduction and a concomitant pericapsular
      acetabuloplasty using a contoured iliac crest allograft as the interposition
      material. The minimum follow up period was 2 years. Measurement of the acetabular
      index (AI) was the main variable. The efficacy of the interposed iliac crest
      allograft as the main stabiliser of the acetabuloplasty was reflected by the
      maintenance of the corrected AI during the follow up period. Loss of acetabular
      correction, graft extrusion or resorption, the need for osteotomy internal
      fixation, delayed or non union, infection, hip redislocation and avascular
      necrosis (AVN) as possible complications were documented. RESULTS: The treatment
      protocol of a combined open reduction of the hip and pericapsular
      acetabuloplasty, inserting a contoured iliac crest allograft as the interposition
      material, resulted in concentrically reduced and stable hips in 96.6% of our
      cases. The redislocation rate was 3.4%. All of the allografts were completely
      incorporated at 6 months post-surgery with no graft-related infections. In only
      two hips was the acetabular correction not maintained. None of the osteotomies
      required internal fixation for stability, even in older children. CONCLUSION: We
      believe that a contoured iliac crest allograft as the pericapsular
      acetabuloplasty interposition material renders excellent osteotomy stability that
      eliminates the need for internal fixation and-in the short-term-maintains the
      correction of the acetabulum achieved intra-operatively.

PMID- 21966308
TI  - Does the Pirani score predict relapse in clubfoot?
AB  - PURPOSE: Presented here is a retrospective clinical audit of clubfoot patients to
      determine the value of the Pirani clubfoot scoring system at initial presentation
      in the estimation of subsequent relapse. METHODS: All clubfoot patients treated
      by the same surgeon from 2002 to 2006 were included. The treatment adhered to the
      standard protocol, involving weekly stretching and casting until the foot was
      corrected, followed by Achilles tenotomy and plasters for 3 weeks. Thereafter,
      the child was placed in a foot abduction splint. The severity of clubfoot was
      assessed using the Pirani scoring system, consisting of two sub-scores-the
      midfoot contracture score (MFCS) and the hindfoot contracture score (HFCS). The
      MFCS and HFCS can each be 0.0-3.0, giving rise to a total Pirani score (TPS) of
      0.0-6.0. Any recurrent deformity was classed as a relapse. RESULTS: Sixty-one
      clubfoot patients were treated. Five patients were lost to follow-up and six
      patients were excluded due to the presence of identified syndromes or having had
      primary treatment elsewhere. A total of 80 clubfeet were included. There were 17
      relapses. The average interval between the initiation of foot abduction splint
      and relapse was 23 months. The median TPS was 3.5 in the no relapse group and 5.0
      in the relapse group. The median MFCS was 1.5 in the no relapse group and 2.0 in
      the relapse group. The median HFCS was 2.0 in the no relapse group and 3.0 in the
      relapse group. Higher TPS and HFCS were statistically significant when the
      relapse group was analysed against the no relapse group (P = 0.05 * 10(-4) and
      0.02 * 10(-4), respectively). CONCLUSIONS: Higher Pirani scores were associated
      with the late relapse group. The TPS and HFCS were shown to be statistically
      significant predictors of potential relapse. Closer follow-up is advised for
      patients at risk of relapse.

PMID- 21966309
TI  - Deformity and functional outcome after treatment for supracondylar humerus
      fractures in children: a 5- to 10-year follow-up of 139 supracondylar humerus
      fractures treated by plaster cast, skeletal traction or crossed wire fixation.
AB  - PURPOSE: At Haukeland University Hospital (HUH), we used overhead skeletal
      traction for displaced supracondylar humerus fractures (SCHF) in children until
      closed reduction and crossed wire fixation was introduced in the early 1990s.
      Though there are obvious and well-documented benefits of wire fixation, the aim
      of this study was to document and compare the results and complication rates for
      both methods. PATIENTS AND METHODS: One hundred and thirty-nine patients treated
      for SCHF between 1988 and 1998 were available for follow-up. Of these, 40
      children were treated with a plaster cast, 46 with overhead skeletal traction and
      45 with crossed wire fixation. Eight children were treated with open reduction
      and crossed wires. The mean time to follow-up was 7.1 years [standard deviation
      (SD) 3.2]. RESULTS: The length of hospital stay was 2 days for those treated with
      crossed wire fixation compared to 11 days for traction (P < 0.001). The rate of
      nerve injury in Gartland type 3 fractures was 19%. There was no significant
      difference in the number of complications or in the functional outcome after
      skeletal traction or wire fixation, but there were more reoperations in the
      traction group (P = 0.04). Patients treated solely with a plaster cast had a mean
      of 4 degrees  increased extension of the affected elbow compared to 1 degrees  in
      the crossed pin fixation group (P = 0.02). Though this has little clinical
      relevance, it does indicate improved reduction in the operated patients, as one
      would expect. CONCLUSIONS: The introduction of crossed wire fixation has
      significantly reduced the number of days for which patients are hospitalised for
      SCHF. The rate of nerve injuries in Gartland type 3 fractures is high. Despite
      the fact that this study includes the first patients to be treated with crossed
      wire fixation at our institution, no significant increase in the risk of
      complications could be found compared to skeletal traction.

PMID- 21966310
TI  - The role of lateral-entry Steinmann pins in the treatment of pediatric
      supracondylar humerus fractures.
AB  - PURPOSE: Loss of pin fixation in supracondylar fractures can occur with failure
      to achieve bicortical fixation. Bicortical fixation may be challenging for those
      pins that attempt to penetrate the diaphyseal cortex, where the bone is thick.
      Lateral-entry Steinmann pins may allow for better penetration through cortical
      bone because they are more rigid than typical Kirschner wires. METHODS: A
      retrospective review of 16 children with type III supracondylar fractures treated
      by a single surgeon using Steinmann pins was undertaken. The average age at
      presentation was 6 years. Following closed reduction, all fractures were
      maintained with three lateral-entry pins. At least one Steinmann pin was placed
      in the lateral column of the distal humerus in each pin construct. RESULTS:
      Follow-up radiographs indicated a mean Baumann's angle of 72.9 degrees  (range 64
      degrees -82 degrees ). There was no statistically significant change in the
      Baumann's angle or axial alignment at final follow-up. All but one fracture
      healed in an anatomic position on the lateral view. CONCLUSIONS: Steinmann pins
      placed through a lateral-entry point are effective in controlling the reduction
      of high-grade supracondylar fractures. The fixation is excellent and avoids
      potential ulnar nerve complications of medial entry.

PMID- 21966311
TI  - Immediate hip spica is as effective as, but more efficient than, flexible
      intramedullary nailing for femoral shaft fractures in pre-school children.
AB  - Flexible intramedullary nailing (FIN) is the gold standard treatment for femur
      fracture in school-aged children. It has been performed successfully in younger
      children, although Spica cast immobilisation (SCI) has been the most widely used
      strategy to date. METHOD: A retrospective analysis was performed between two
      comparable groups of children aged 1-4 years with a femoral shaft fracture. Two
      University hospitals, each using specific treatment guidelines, participated in
      the study: SCI in Group I (Basel, Switzerland) and FIN in Group II (Lausanne,
      Switzerland). RESULTS: Group I included 19 children with a median age of 26
      months (range 12-46 months). Median hospital stay was 1 day (range 0-5 days) and
      casts were retained for a median duration of 21 days (range 12-29 days). General
      anaesthesia was used in six children and sedation in four. Skin breakdown
      secondary to cast irritation occurred in two children (10.5%). The median follow
      up was 114 months (range 37-171 months). No significant malunion was noted. Group
      II included 27 children with a median age of 38.4 months (range 18.7-46.7
      months). Median hospital stay was 4 days (range 1-13 days). All children required
      general anaesthesia for insertion and removal of the nails. Free mobilisation and
      full weight bearing were allowed at a median of 2 days (range 1-10 days) and 7
      days (range 1-30 days), respectively, postoperatively. Nail exteriorisation was
      noted in three children (11%). The median follow-up was 16.5 months (range 8-172
      months). No significant malunion was reported. CONCLUSIONS: Young children with a
      femoral shaft fracture treated by SCI or FIN had similarly favourable outcomes
      and complication rates. FIN allowed earlier mobilisation and full weight bearing.
      Compared to SCI, a greater number of children required general anaesthesia. In a
      pre-school child with a femoral shaft fracture, immediate SCI applied by a
      paediatric orthopaedic team following specific guidelines allowed early discharge
      from hospital with few complications.

PMID- 21966312
TI  - Skeletal and chronological ages in American adolescents: current findings in
      skeletal maturation.
AB  - PURPOSE: This study was designed to assess the relationship between skeletal and
      chronological ages among current American adolescents using the Greulich and Pyle
      atlas for skeletal age determination. MATERIALS AND METHODS: We used the Greulich
      and Pyle atlas to prospectively determine skeletal age in a group of 138
      otherwise healthy American adolescents from 12 to 18 years of age. 62 males and
      76 females were enrolled in this cohort. Paired Student t-tests were used to
      statistically compare the skeletal and chronological ages in this population.
      Subgroup analysis examined the effect of gender on differences between
      chronologic age and skeletal age. RESULTS: For the entire cohort, mean skeletal
      age was significantly greater than chronological age (mean 0.80 years, P < 0.01).
      In 29 cases (21%) the skeletal age was at least 2 years greater than the
      chronologic age. Among females, such cases with marked discrepancy occurred
      exclusively in those chronologically between 12 and 15 years of age (P < 0.01).
      Males demonstrated a 2-year or greater discrepancy more commonly than females (26
      vs. 17%). In males, 2-year discrepancies were equally likely across chronologic
      ages (P = 0.82). CONCLUSIONS: Current American adolescents are significantly more
      mature by skeletal age, as determined by the Greulich and Pyle method, than their
      chronological age would suggest. The skeletal ages of females are most likely to
      markedly exceed chronologic age between the ages of 12-15 years.

PMID- 21966313
TI  - A review of reported litigation against English health trusts for the treatment
      of children in orthopaedics: present trends and suggestions to reduce mistakes.
AB  - PURPOSE: Large scale databases that offer a reflection of clinical negligence are
      rare. By assessing commonly occuring cases of negligence, we hope to highlight
      areas where pediatric orthopedic care might be improved. One such database is the
      National Health Service Litigation Authority, which deals with claims brought
      against all health trusts in England. By collating their data we aimed to
      highlight areas of commonly occurring clinical negligence and then suggest ways
      to avoid similar happening again. METHOD: We reviewed all cases pertaining to
      pediatric orthopedic claims between 1995 to 2006 as provided by the NHSLA.
      RESULTS: Of those considered in our study (341), by far the most common cause of
      litigation is missed or incorrectly diagnosed injuries/ conditions-accounting for
      57% of all cases. 44% of those are upper limb injuries, mainly fractures around
      the elbow. Misdiagnosed disorders of the hip such as hip dysplasia and SCFE also
      represent a frequent reason for litigation (11%). Other common causes are poor
      plaster application and removal (7.3%) and non-surgical site specific errors such
      as chemical burns from skin prep. CONCLUSION: Although specific to the English
      system, these findings are likely to mirror that found in other countries.
      Highlighting these commonly occurring errors, better education of doctors in
      targeted areas and due care in simple procedures may have significant improvement
      of child orthopedic care.

PMID- 21966314
TI  - Erratum to: Missed Monteggia fracture in children: is annular ligament
      reconstruction always required?

PMID- 21966315
TI  - Local versus specialized treatment: the difficulty in interpreting regional
      variations in treatment.

PMID- 21966316
TI  - Standardized prehospital treatment of stroke.
AB  - BACKGROUND: The lack of standardized pre-hospital treatment is a weak link in the
      care of acute stroke patients. METHODS: Selective review of the literature on
      acute stroke, with consideration of current guidelines in Germany and other
      countries (DGN, ESO, AHA/ASA). RESULTS: The mandatory, immediate transfer of
      acute stroke patients to a specialized stroke unit is supported by high-level
      evidence. Simple, sensitive screening tests for the diagnosis of stroke are
      available that can be performed in the field by trained non-physician emergency
      medical personnel. With regard to pre-hospital treatment, adequate scientific
      evidence supports cardiopulmonary stabilization, as well as oxygen
      supplementation if there are signs of hypoxemia. The patient's neurological
      findings, time of onset of symptoms, current medications, and past medical and
      surgical history must all be precisely and thoroughly documented. The receiving
      hospital must be informed of the patient's impending arrival as early as
      possible, particularly in cases where recanalizing procedures are still a
      therapeutic option. Treatment with aspirin or heparin must not be started in
      situ, i.e. without prior cerebral imaging. CONCLUSION: In the pre-hospital phase
      of stroke care delivery, the goal of a high capture rate can best be achieved
      through the use of appropriate diagnostic tests with maximal sensitivity.
      Patients with suspected acute stroke should be given the highest priority for
      transfer to a specialized stroke unit. Optimal pre-hospital care requires the
      smoothly functioning cooperation of all professionals involved, from the triaging
      and nursing personnel to the paramedics, dispatchers, emergency physicians in the
      field, and admitting physicians in the hospital.

PMID- 21966317
TI  - Predictors of dependency on nursing care after stroke: results from the Dortmund
      and Munster stroke registry.
AB  - BACKGROUND: The long-term effects of stroke have been inadequately studied. We
      identified social and clinical factors that were associated with application for
      insurance payments for long-term care within 3.6 years after stroke. METHODS: In
      a quality-assurance project called "Stroke Northwest Germany," information was
      obtained from 2286 stroke patients on their socio-demographic background, type of
      stroke, comorbidities, and degree of physical impairment during their hospital
      stay, as measured on the Rankin Scale, the Barthel Index, and the Neurological
      Symptom Scale. We used logistic regression models to identify possible
      associations between these factors and application for insurance payments for
      long-term care within 3.6 years after stroke. We developed an appropriate
      prognostic model by means of backward selection. RESULTS: 734 (32.1%) of the
      patients participated in follow-up and reported whether they had applied for
      insurance payments for long-term care. 22.5% had submitted an application. The
      rate of application was positively correlated with age, female sex, the number of
      comorbidities and complications during hospitalization, and the degree of
      physical impairment. CONCLUSION: Stroke has major long-term effects. The
      probability that a stroke patient will apply for insurance payments for long-term
      care is a function of the patient's age, sex, previous stroke history, and
      physical impairment as measured on the Rankin Scale and the Barthel Index.

PMID- 21966318
TI  - Rehabilitation after stroke.
AB  - BACKGROUND: Stroke is becoming more common in Germany as the population ages. Its
      long-term sequelae can be alleviated by early reperfusion in stroke units and by
      complication management and functional restoration in early-rehabilitation and
      rehabilitation centers. METHODS: Selective review of the literature. RESULTS:
      Successful rehabilitation depends on systematic treatment by an interdisciplinary
      team of experienced specialists. In the area of functional restoration, there has
      been major progress in our understanding of the physiology of learning,
      relearning, training, and neuroenhancement. There have also been advances in
      supportive pharmacotherapy and robot technology. CONCLUSION: Well-organized acute
      and intermediate rehabilitation after stroke can provide patients with the best
      functional results attainable on the basis of our current scientific
      understanding. Further experimental and clinical studies will be needed to expand
      our knowledge and improve the efficacy of rehabilitation.

PMID- 21966319
TI  - Regional differences in acute stroke admission and thrombolysis rates in the
      German federal state of Hesse.
AB  - BACKGROUND: Using data from the mandatory quality assurance program for stroke
      care in Hesse, we analyze regional differences in thrombolysis rates and infer
      some ways in which care can be improved. METHODS: We identified 7707 patients
      with acute ischemic stroke who were admitted to hospital within 3 hours of
      symptom onset in 2007 and 2008, and we determined the local thrombolysis rate
      district by district. In order to exclude the possibility that the observed local
      differences in thrombolysis rates might be accounted for, in large part, by off
      label thrombolysis procedures, we further narrowed down the subgroup of patients
      who underwent thrombolysis to the 1108 patients admitted within 2 hours of
      symptom onset. We also analyzed the local thrombolysis rates for patients who
      were primarily referred to stroke units. RESULTS: The overall thrombolysis rate
      among patients admitted within 3 hours of symptom onset was 19%, varying locally
      from 6% to 35%. Among patients admitted within 2 hours of symptom onset, the
      local thrombolysis rate ranged from 13% to 85%. Even in patients primarily
      referred to stroke units, the local thrombolysis rate ranged from 8% to 44% in
      the 3-hour group and from 16% to 62% in the 2-hour group. CONCLUSION: Local
      thrombolysis rates vary unexpectedly widely across the state of Hesse. The care
      of patients with acute stroke after they reach the hospital urgently needs
      critical reappraisal and improvement.

PMID- 21966320
TI  - Correspondence (letter to the editor): pre-existing conditions are no barrier to
      strength training.

PMID- 21966321
TI  - Correspondence (letter to the editor): effectiveness in the obese.

PMID- 21966322
TI  - Using Multiple Control Groups and Matching to Address Unobserved Biases in
      Comparative Effectiveness Research: An Observational Study of the Effectiveness
      of Mental Health Parity.
AB  - Studies of large policy interventions typically do not involve randomization.
      Adjustments, such as matching, can remove the bias due to observed covariates,
      but residual confounding remains a concern. In this paper we introduce two
      analytical strategies to bolster inferences of the effectiveness of policy
      interventions based on observational data. First, we identify how study groups
      may differ and then select a second comparison group on this source of
      difference. Second, we match subjects using a strategy that finely balances the
      distributions of key categorical covariates and stochastically balances on other
      covariates. An observational study of the effect of parity on the severely ill
      subjects enrolled in the Federal Employees Health Benefits (FEHB) Program
      illustrates our methods.

PMID- 21966323
TI  - The traumatized ischiopubic synchondrosis: a rare cause of acute hip pain.

PMID- 21966324
TI  - Expression of histone deacetylases in cellular compartments of the mouse brain
      and the effects of ischemia.
AB  - Drugs that inhibit specific histone deacetylase (HDAC) activities have enormous
      potential in preventing the consequences of acute injury to the nervous system
      and in allaying neurodegeneration. However, very little is known about the
      expression pattern of the HDACs in the central nervous system (CNS). Identifying
      the cell types that express HDACs in the CNS is important for determining
      therapeutic targets for HDAC inhibitors and evaluating potential side effects. We
      characterized the cellular expression of HDACs 1-3, and HDACs 4 and 6, in the
      adult mouse brain in the cingulate cortex, parietal cortex, dentate gyrus, and
      CA1 regions of the hippocampus and subcortical white matter. Expression of class
      I HDACs showed a cell-and region-specific pattern. Transient focal ischemia
      induced by temporary middle cerebral artery occlusion, or global ischemia induced
      by in vitro oxygen-glucose deprivation, altered the extent of HDAC expression in
      a region- and cell-specific manner. The pan-HDAC inhibitor, SAHA, reduced
      ischemia-induced alterations in HDACs. The results suggest that in addition to
      promoting epigenetic changes in transcriptional activity in the nucleus of
      neurons and glia, HDACs may also have non-transcriptional actions in axons and
      the distant processes of glial cells and may significantly modulate the response
      to injury in a cell- and region-specific manner. 

PMID- 21966325
TI  - In the Huh7 Hepatoma Cells Diclofenac and Indomethacin Activate Differently the
      Unfolded Protein Response and Induce ER Stress Apoptosis.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are cyclooxygenases (COXs)
      inhibitors frequently used in the treatment of acute and chronic inflammation.
      Side effects of NSAIDs are often due to their ability to induce apoptosis.
      Located at the Endoplasmic Reticulum membranes a tripartite signalling pathway,
      collectively known as the Unfolded Protein Response (UPR), decides survival or
      death of cells exposed to cytotoxic agents. To shed light on the molecular events
      responsible for the cytotoxicity of NSAIDs, we analysed the ability of diclofenac
      and indomethacin to activate the UPR in the human hepatoma cell line Huh7. We
      report that both NSAIDs can induce differently the single arms of the UPR. We
      show that indomethacin turns on the PERK and, only in part, the ATF6 and IRE1
      pathways. Instead, diclofenac reduces the expression of ATF6 and does not
      stimulate the IRE1 endonuclease, which drives the expression of the prosurvival
      factor XBP1. Diclofenac, as well as indomethacin, is able to activate efficiently
      only the PERK pathway of the UPR, which induces the expression of the
      proapoptotic GADD153/CHOP protein. Our results highlight the importance of the
      UPR in evaluating the potential of drugs to induce apoptosis.

PMID- 21966326
TI  - Medicinal chemistry of novel anti-diabetic drugs.

PMID- 21966327
TI  - Medicinal chemistry of the anti-diabetic effects of momordica charantia: active
      constituents and modes of actions.
AB  - Diabetes mellitus (DM) is one of the oldest known human disease currently
      affecting more than 200 million people worldwide. Diabetes mellitus is derived
      from two Greek words meaning siphon and sugar. In DM, patients have high blood
      level of glucose and this passes out with urine. This is because the endocrine
      pancreas does not produce either or not enough insulin or the insulin which is
      produced is not exerting its biochemical effect (or insulin resistance)
      effectively. Insulin is a major metabolic hormone which has numerous functions in
      the body and one main role is to stimulate glucose uptake into body's cells where
      it is utilized to provide energy. The disease is classified into type 1 and type
      2 DM. Type 1 DM develops when the insulin producing beta cells have been
      destroyed and are unable to produce insulin. This is very common in children and
      is treated with insulin. Type 2 DM (T2DM) develops when the body is unable to
      produce an adequate amount of insulin or the insulin which is provided does not
      work efficiently. This is due to life style habits including unhealthy diet,
      obesity, lack of exercise and hereditary and environmental factors. Some symptoms
      of DM include excess urination, constant thirst, lethargy, weight loss, itching,
      decreased digestive enzyme secretion, slow wound healing and other related
      symptoms. If left untreated, DM can result in severe long-term complications such
      as kidney and heart failure, stroke, blindness, nerve damage, exocrine glands
      insufficiency and other forms of complications. T2DM can be treated and
      controlled by prescribed drugs, regular exercise, diet (including some plant
      based food) and general change in life style habits. This review is concerned
      with the role of plant-based medicine to treat DM. One such plant is Momordica
      charantia which is grown in tropical countries worldwide and it has been used as
      a traditional herbal medicine for thousands of years although its origin in
      unknown. This review examines the medicinal chemistry and use(s) of M. charantia
      and its various extracts and compounds, their biochemical properties and how they
      act as anti-diabetic (hypoglycemic) drugs and the various mechanisms by which
      they exert their beneficial effects in controlling and treating DM.

PMID- 21966328
TI  - Amylin analogues in the treatment of diabetes mellitus: medicinal chemistry and
      structural basis of its function.
AB  - Amylin, (islet amyloid polypeptide) or diabetes-associated peptide is co-secreted
      with insulin in the islet of Langerhans of diabetic patients in approximately
      1:100, amylin-insulin ratio. The soluble form of amylin, an analogue of amylin,
      is used as a supplement to insulin in the treatment of type 1 diabetes. Co
      administration of amylin analogue with insulin to patients with type 1 diabetes
      induced a larger reduction in proprandial hyperglycemia, with a concomitant
      reduction in the level of glucagon when compared to insulin monotherapy. The
      actions of amylin analogues appear to be synergistic to insulin, with which it is
      co-released from insulin-producing beta cells after a meal. Amylin analogues such
      as pramlintide has been shown to significantly reduce body weight, HbA1c values
      and even the dosage of insulin. A moderate weight loss can also be achieved in
      obese patients with or without diabetes. A major side effect of some amylin
      analogues includes nausea and excitation of the area postrema. This review
      examines the medicinal chemistry of amylin and its analogues and their effects.

PMID- 21966329
TI  - Medicinal Chemistry and Applications of Incretins and DPP-4 Inhibitors in the
      Treatment of Type 2 Diabetes Mellitus.
AB  - Diabetes mellitus (DM) is a major metabolic disorder currently affecting over 200
      million people worldwide. Approximately 90% of all diabetic patients suffer from
      Type 2 diabetes mellitus (T2DM). The world's economy coughs out billions of
      dollars annually to diagnose, treat and manage patients with diabetes. It has
      been shown that the naturally occurring gut hormones incretins, glucose-dependent
      insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) can preserve
      the morphology and function of pancreatic beta cell. In addition, GIP and GLP-1
      act on insulin receptors to facilitate insulin-receptor binding, resulting in
      optimal glucose metabolism. This review examines the medicinal chemistry and
      roles of incretins, specifically, GLP-1 and drugs which can mimic its actions and
      prevent its enzymatic degradation. The review discussed GLP-1 agonists such as
      exenatide, liraglutide, taspoglutide and albiglutide. The paper also identified
      and reviewed a number of inhibitors, which can block dipeptidyl peptidase 4 (DPP
      4), the enzyme responsible for the rapid degradation of GLP-1. These DPP-4
      inhibitors include sitagliptin, saxagliptin, vildagliptin and many others which
      are still in the experimental phase.

PMID- 21966330
TI  - Medicinal Chemistry and Actions of Dual and Pan PPAR Modulators.
AB  - Peroxisome proliferator-activated receptor (PPAR) agonists are used as adjunct
      therapy in the treatment of diabetes mellitus. Fibrates, including fenofibrate,
      gemfibrozil, benzafibrate, ciprofibrate, and clofibrate act on PPAR alpha to
      reduce the level of hypertriglyceridemia. However, agonists (ligands) of PPAR
      beta/delta receptors, such as tesaglitazar, muraglitazar, ragaglitazar,
      imiglitazar, aleglitazar, alter the body's energy substrate preference from
      glucose to lipids and hence contribute to the reduction of blood glucose level.
      Glitazones or thiazolidinediones on the other hand, bind to PPAR-gamma receptors
      located in the nuclei of cells. Activation of PPAR-gamma receptors leads to a
      decrease in insulin resistance and modification of adipocyte metabolism. They
      reduce hyperlipidaemia by increasing the level of ATP-binding cassette A1, which
      modifies extra-hepatic cholesterol into HDL. Dual or pan PPAR ligands stimulate
      two or more isoforms of PPAR and thereby reduce insulin resistance and prevent
      short- and long-term complications of diabetes including micro-and
      macroangiopathy and atherosclerosis, which are caused by deposition of
      cholesterol. This review examines the chemical structure, actions, side effects
      and future prospects of dual and pan PPAR agonists.

PMID- 21966331
TI  - Prevalence, Predictors, and Impact of Low High-Density Lipoprotein Cholesterol on
      in-Hospital Outcomes Among Acute Coronary Syndrome Patients in the Middle East.
AB  - OBJECTIVE: To estimate the prevalence, predictors, and impact of low high-density
      lipoprotein cholesterol (HDL-C) on in-hospital outcomes among acute coronary
      syndrome (ACS) patients in the Middle East. METHODS: Data were collected
      prospectively from 6,266 consecutive patients admitted with a diagnosis of ACS
      and enrolled in the Gulf Registry of Acute Coronary Events (Gulf RACE). A low HDL
      C was defined as a level <40 mg/Dl (1.0 mmol/L) for males and <50 mg/dL (1.3
      mmol/L) for females. Analyses were performed using univariate and multivariate
      statistical techniques. RESULTS: The overall mean age of the cohort was 56+/-12
      years and majority were males (77%). The overall prevalence of low HDL-C was 62%.
      During in-hospital stay and at discharge, the majority were on statin therapy
      (83%) while 10% were on other cholesterol lowering agents. After adjustment of
      demographic and clinical characteristics, the predictors for low HDL-C were
      higher body mass index (BMI), prior myocardial infarction (MI), diabetes
      mellitus, smoking and impaired renal function. Multivariable adjustment revealed
      that low HDL-C was associated with higher in-hospital mortality (odds ratio (OR),
      1.54; 95% CI: 1.06-2.24; p=0.022) and cardiogenic shock (OR, 1.61; 95% CI: 1.20
      2.14; p=0.001). CONCLUSIONS: ACS patients in the Middle East have a high
      prevalence of low HDL-C. Higher BMI, prior MI, diabetes mellitus, smoking, and
      impaired renal function were predictors of low HDL-C. Significantly higher in
      hospital mortality and cardiogenic shock were associated with low HDL-C in men
      but not in women.

PMID- 21966332
TI  - Type IV Ehlers-Danlos Syndrome: A Surgical Emergency? A Case of Massive
      Retroperitoneal Hemorrhage.
AB  - Retroperitoneal hemorrhagic bleeding is a known manifestation of Type-IV Ehlers
      Danlos Syndrome that is caused by loss-of-function mutations of the pro-alpha-1
      chains of type III pro-collagen (COL3A1) resulting in vascular fragility. A
      number of previous reports describe futile surgical intervention for
      retroperitoneal bleeding in Type-IV Ehlers-Danlos Syndrome with high post
      operative mortality, although the rarity of retroperitoneal bleeding associated
      with Type-IV Ehlers-Danlos Syndrome precludes an evidence-based approach to
      clinical management. We report a 23-year-old male with history of Type-IV Ehlers
      Danlos Syndrome who presented with severe abdominal pain and tachycardia
      following an episode of vomiting. Further work-up of his abdominal pain revealed
      massive retroperitoneal bleeding by CT-scan of the abdomen. Given numerous cases
      of catastrophic injury caused by surgical intervention in Type-IV Ehlers-Danlos
      Syndrome, the patient was treated non-operatively, and the patient made a full
      recovery. This case suggests that even in cases of large retroperitoneal
      hemorrhages associated with Ehlers-Danlos Syndrome, it may not truly represent a
      surgical emergency.

PMID- 21966333
TI  - A dilated odontoma in the second molar region of the mandible.
AB  - A case of dilated odontoma in the second molar region of the mandible was
      reported. The patient was a 14-year-old female. Panoramic X-ray and CT
      examination revealed an oval ring-shaped radiopaque lesion accompanying a
      radiolucent area in the center at the left second molar region of the mandible.
      The left second molar and all third molars were not found. The lesion was
      diagnosed as odontoma and extirpated under general anesthesia. The lesion was a
      spherical mass of 12x9mm. Histologically, the mass was composed of dentin
      arranged in an oval ring shape with dentinal tubules. Inside the dentin, immature
      enamel was present. The central area of the mass was filled with fibrous tissue
      with a small nest of bone and cementum. Bone tissue was also observed in contact
      with the immature enamel layer. These morphological and histological features are
      compatible with those of a dilated odontoma.

PMID- 21966334
TI  - Self reported halitosis in relation to glycated hemoglobin level in diabetic
      patients.
AB  - OBJECTIVE: This study was conducted to examine the relationship between the
      glycated hemoglobin level (HbA1c) and halitosis status among diabetic patients
      affected with periodontitis and to examine if there is a relationship between
      halitosis and different periodontal parameters. METHODS AND MATERIALS:
      Consecutive type 2 diabetic patients were recruited from patients presented for
      treatment at a University hospital. Age, gender and smoking were recorded. A
      structured questionnaire on patients' perception of their oral health, halitosis
      and diabetes severity and control was completed. Peripheral blood samples were
      obtained and analyzed for HbA1c levels. In addition, periodontal clinical
      parameters including probing depth, clinical attachment level, bleeding on
      probing and plaque scores were recorded. RESULTS: A total of 38 type 2 diabetic
      patients were selected. The mean age was 52.1 (+/-8.8) years. Sixteen subjects
      (42.1%) reported halitosis. Of these, 62.5% were females, and only one subject
      was a current smoker. The mean levels of HbA1c were significantly different
      between those with and without halitosis, mean 9.6 (+/-2) and 8.2 (+/-1.6),
      respectively (p=0.03). No significant differences were found in the mean
      periodontal parameters between those with and without halitosis. CONCLUSION: The
      results of this study suggest an association between halitosis and increased
      levels of HbA1c. Further studies are needed to explain the nature of this
      association.

PMID- 21966335
TI  - A review on prevention and treatment of post-orthodontic white spot lesions -
      evidence-based methods and emerging technologies.
AB  - OBJECTIVE: The aim of this paper was to update the evidence for primary and
      secondary prevention (treatment) of white spot lesions (WSL) adjacent to fixed
      orthodontic appliances. MATERIAL AND METHODS: A search for relevant human
      clinical trials published in English between 2004 and March 2011 retrieved 25
      publications that fulfilled the inclusion criteria. The papers were assessed for
      prevented fraction and/or absolute risk reduction when possible. RESULTS AND
      CONCLUSIONS: The findings consolidated the use of topical fluorides in addition
      to fluoride toothpaste as the best evidence-based way to avoid WSL. The mean
      prevented fraction based on 6 trials was 42.5% with a range from -4% to 73%. The
      recent papers provided the strongest support for regular professional
      applications of fluoride varnish around the bracket base during the course of
      orthodontic treatment. For the treatment of post-orthodontic WSL, home-care
      applications of a remineralizing cream, based on casein phosphopeptide-stabilized
      amorphous calcium phosphate, as adjunct to fluoride toothpaste could be
      beneficial but the findings were equivocal. For emerging technologies such as
      sugar alcohols and probiotics, still only studies with surrogate endpoints are
      available. Thus, further well-designed studies with standardized regimes and
      endpoints are needed before guidelines on the non-fluoride technologies can be
      recommended.

PMID- 21966336
TI  - Bone mineral density in healthy female adolescents according to age, bone age and
      pubertal breast stage.
AB  - OBJECTIVES: This study was designed to evaluate bone mineral density (BMD) in
      healthy female Brazilian adolescents in five groups looking at chronological age,
      bone age, and pubertal breast stage, and determining BMD behavior for each
      classification. METHODS: Seventy-two healthy female adolescents aged between 10
      to 20 incomplete years were divided into five groups and evaluated for calcium
      intake, weight, height, body mass index (BMI), pubertal breast stage, bone age,
      and BMD. Bone mass was measured by bone densitometry (DXA) in lumbar spine and
      proximal femur regions, and the total body. BMI was estimated by Quetelet index.
      Breast development was assessed by Tanner's criteria and skeletal maturity by
      bone age. BMD comparison according to chronologic and bone age, and breast
      development were analyzed by Anova, with Scheffe's test used to find significant
      differences between groups at P<=0.05. RESULTS: BMD (g.cm(-2)) increased in all
      studied regions as age advanced, indicating differences from the ages of 13 to 14
      years. This group differed to the 10 and 11 to 12 years old groups for lumbar
      spine BMD (0.865+/-0.127 vs 0.672+/-0.082 and 0.689+/-0.083, respectively) and in
      girls at pubertal development stage B3, lumbar spine BMD differed from B5
      (0.709+/-0.073 vs 0.936+/-0.130) and whole body BMD differed from B4 and B5
      (0.867+/-0.056 vs 0.977+/-0.086 and 1.040+/-0.080, respectively). CONCLUSION:
      Bone mineralization increased in the B3 breast maturity group, and the critical
      years for bone mass acquisition were between 13 and 14 years of age for all sites
      evaluated by densitometry.

PMID- 21966337
TI  - Treatment of osteitis pubis in non-athlete female patients.
AB  - BACKGROUND: Osteitis pubis represents a non-infectious inflammation of the pubic
      symphysis causing varying degrees of lower abdominal and pelvic pain. Although,
      the disease is believed to affect mainly young athletic patients, it is also
      encountered in other specific patient groups. Both conservative and surgical
      treatment options are available. While for elite athletes surgical treatment is
      indicated, leading to fast pain relief and mobilization, for non-athletic
      patients no clear indication can be established. METHODS: Eight non-athletic
      women with osteitis pubis, referred to our Department for treatment, were
      evaluated. All were initially treated conservatively with bed rest, per os non
      steroidal anti-inflammatory drugs and physical therapy. RESULTS: Seven patients
      improved significantly with conservative treatment while one displayed no
      improvement and was treated surgically with arthrodesis. CONCLUSION: We conclude
      that, for non-athletic female patients suffering from osteitis pubis, surgery is
      rarely required and that conservative treatment by means of non steroidal anti
      inflammatory drugs and physical modalities represents a fair option regarding
      pain and limitation of everyday activity.

PMID- 21966338
TI  - Pathophysiology and biomechanics of the aging spine.
AB  - AGING OF THE SPINE IS CHARACTERIZED BY TWO PARALLEL BUT INDEPENDENT PROCESSES:
      the reduction of bone mineral density and the development of degenerative
      changes. The combination of degeneration and bone mass reduction contribute, to a
      different degree, to the development of a variety of lesions. This results in a
      number of painful and often debilitating disorders. The present review
      constitutes a synopsis of the pathophysiological processes that take place in the
      aging spine as well as of the consequences these changes have on the biomechanics
      of the spine. The authors hope to present a thorough yet brief overview of the
      process of aging of the human spine.

PMID- 21966339
TI  - Evaluation of improvement in quality of life and physical activity after total
      knee arthroplasty in greek elderly women.
AB  - BACKGROUND: The aim of this study was to evaluate the changes in quality of life
      of patients after total knee arthroplasty and to assess the changes in physical
      activity by using a self-reported questionnaire and by counting the number of
      steps 3-6 months after post-operatively. METHODS: Included were fifty two elderly
      women (age 72.6+/-65.9 years, mean+/-SD) with knee osteoarthritis undergoing
      primary knee arthroplasty. Health-related quality of life, physical activity,
      pain and function and the number of steps were assessed before, 3 and 6 months
      post-operatively. We used the Medical Outcomes Study Short Form (SF-36), the
      Physical Activity Scale for the Elderly (PASE) and the pedometer SW200 Digiwalker
      of Yamax. RESULTS: Patients showed a significant improvement (p< 0.01, eta2
      =0.22) in health-related quality of life, particularly in physical function, (p<0
      .001) body pain (p< 0.001) and vitality scale (p< 0.001) of SF-36 at 3 and 6
      months after the procedure. Physical activity (PASE score) increased at 3 and 6
      months after arthroplasty (p< 0.001, eta2 =0.74), and the number of steps
      increased 6 months after, compared to the assessment that took place 3 months
      after operation (p< 0.001). CONCLUSIONS: Our results suggest that total knee
      arthroplasty leads to a gradual improvement in quality of life of elderly
      patients over the first 6 post-operative months.

PMID- 21966340
TI  - Adult mesenchymal stem cells and cell surface characterization - a systematic
      review of the literature.
AB  - Human adult mesenchymal stem cells (MSCs) were first identified by Friedenstein
      et al. when observing a group of cells that developed into fibroblastic colony
      forming cells (CFU-F). Ever since, the therapeutic uses and clinical applications
      of these cells have increased research and interest in this field. MSCs have the
      potential to be used in tissue engineering, gene therapy, transplants and tissue
      injuries. However, identifying these cells can be a challenge. Moreover, there
      are no articles bringing together and summarizing the cell surface markers of
      MSCs in adults. The purpose of this study is to summarize all the available
      information about the cell surface characterization of adult human MSCs by
      identifying and evaluating all the published literature in this field. We have
      found that the most commonly reported positive markers are CD105, CD90, CD44,
      CD73, CD29, CD13, CD34, CD146, CD106, CD54 and CD166. The most frequently
      reported negative markers are CD34, CD14, CD45, CD11b, CD49d, CD106, CD10 and
      CD31. A number of other cell surface markers including STRO-1, SH2, SH3, SH4, HLA
      A, HLA-B, HLA-C, HLA-DR, HLA-I, DP, EMA, DQ (MHC Class II), CDIO5, Oct 4, Oct 4A,
      Nanog, Sox-2, TERT, Stat-3, fibroblast surface antigen, smooth muscle alpha
      actin, vimentin, integrin subunits alpha4, alpha5, beta1, integrins alphavbeta3
      and alphavbeta5 and ICAM-1 have also been reported. Nevertheless, there is great
      discrepancy and inconsistency concerning the information available on the cell
      surface profile of adult MSCs and we suggest that further research is needed in
      this field to overcome the problem.

PMID- 21966341
TI  - The insertion of fluorescent proteins in a variable region of respiratory
      syncytial virus L polymerase results in fluorescent and functional enzymes but
      with reduced activities.
AB  - The respiratory syncytial virus (RSV) Large protein L is the catalytic subunit of
      the RNA-dependent RNA polymerase complex. Currently, no structural information is
      available for RSV L. Sequence alignments of L protein from human and bovine
      strains of RSV revealed the existence of two variable regions, VR1 and VR2.
      Following comparison with morbillivirus and rhabdovirus L genes, VR2, which is
      located between domains V and VI, was chosen as an insertion site for sequences
      encoding the epitope tag HA or the fluorescent proteins eGFP and mCherry.
      Recombinant tagged-L proteins co-localized with RSV N and P proteins in
      transfected cells. These recombinant polymerases were shown to be functional
      using a viral minigenome system assay, their activities being reduced by ~70%
      compared to the unmodified L polymerase. We have also shown by site-directed
      mutagenesis that the GDNQ motif (residues 810-813 for the Long strain of HRSV) is
      essential for L activity.

PMID- 21966342
TI  - Phytochemical and Bioactivity Studies on Constituents of the Leaves of Vitex
      Quinata.
AB  - A phytochemical investigation of the leaves of Vitex quinata (Lour.) F.N.
      Williams (Verbenaceae), guided by the MCF-7 human breast cancer cell line, led to
      the isolation of a new delta-truxinate derivative (1) and a new phytonoic acid
      derivative (2), together with 12 known compounds. The structures of the new
      compounds were determined by spectroscopic methods as dimethyl 3,4,3',4'
      tetrahydroxy-delta-truxinate (1) and methyl 10R-methoxy-12-oxo-9(13),16E
      phytodienoate (2), respectively. In a cytotoxicity assay, (S)-5-hydroxy-7,4'
      dimethoxyflavanone (3) was found to be the sole active principle, with ED(50)
      values of 1.1-6.7 MUM, respectively, when tested against a panel of three human
      cancer cells. Methyl 3,4,5-O-tricaffeoyl quinate (4) showed activity in an enzyme
      based ELISA NF-kappaB p65 assay, with an ED(50) value of 10.3 MUM.

PMID- 21966343
TI  - The motivated brain: insights from neuroimaging studies of human male sexual
      affiliation context.
AB  - The advent of functional neuroimaging techniques has allowed to address the
      question of the role of the brain in a new light, being now able to record brain
      activity under different kinds of perceptual, cognitive or motor paradigms. Two
      exponentially emerging fields, i.e. social and affective neurosciences, converge
      on topics such as brain processing of emotional information issued by the
      congeners. As any social interaction obbeys a motivational dimension of
      interattraction, it is therefore important to study the role of the brain in
      specific functional contexts. In this paper we show how the emergence of a new
      field crystallized around the study of brain circuits involved in sexual
      affiliation has helped providing important results to understand the brain's role
      in social motivated interactions. Specifically, these studies show for this
      involvement a central physiological component and its cortical representation
      that seems to be essential for social interactions with motivational component.

PMID- 21966344
TI  - Catalytic specificity of human protein tyrosine kinases revealed by Peptide
      substrate profiling.
AB  - Out of the 90 human protein tyrosine kinases, 81 were assayed with short peptides
      derived from well-characterized [CDK1(Tyr15), IRS1(Tyr983), and JAK1(Tyr1023)] or
      generic [polyGlu:Tyr(4:1) and poly-Glu:Ala:Tyr(1:1:1)] substrates. As expected,
      the CDK1 peptide is a substrate for all Src family kinases. On the other hand,
      some of the activities are novel and lead to a better understanding of the
      function of certain kinases. Specifically, the CDK1 peptide is a substrate for
      many of the Eph family members. Interestingly, profiling of nearly all the human
      protein tyrosine kinases revealed a distinct pattern of selectivity towards the
      CDK1 and IRS1 peptides.

PMID- 21966345
TI  - Promoting illiteracy in epigenetics: an emerging therapeutic strategy.

PMID- 21966346
TI  - Chemical biology of lysine demethylases.
AB  - Abnormal levels of DNA methylation and/or histone modifications are observed in
      patients with a wide variety of chronic diseases. Methylation of lysines within
      histone tails is a key modification that contributes to increased gene expression
      or repression depending on the specific residue and degree of methylation, which
      is in turn controlled by the interplay of lysine methyl transferases and
      demethylases. Drugs that target these and other enzymes controlling chromatin
      modifications can modulate the expression of clusters of genes, potentially
      offering higher therapeutic efficacy than classical agents acting on downstream
      biochemical pathways that are susceptible to degeneracy. Lysine demethylases,
      first discovered in 2004, are the subject of increasing interest as therapeutic
      targets. This review provides an overview of recent findings implicating lysine
      demethylases in a range of therapeutic areas including oncology,
      immunoinflammation, metabolic disorders, neuroscience, virology and regenerative
      medicine, together with a summary of recent advances in structural biology and
      small molecule inhibitor discovery, supporting the tractability of the protein
      family for the development of selective druglike inhibitors.

PMID- 21966348
TI  - Structural Chemistry of Human SET Domain Protein Methyltransferases.
AB  - There are about fifty SET domain protein methyltransferases (PMTs) in the human
      genome, that transfer a methyl group from S-adenosyl-L-methionine (SAM) to
      substrate lysines on histone tails or other peptides. A number of structures in
      complex with cofactor, substrate, or inhibitors revealed the mechanisms of
      substrate recognition, methylation state specificity, and chemical inhibition.
      Based on these structures, we review the structural chemistry of SET domain PMTs,
      and propose general concepts towards the development of selective inhibitors.

PMID- 21966347
TI  - Targets in epigenetics: inhibiting the methyl writers of the histone code.
AB  - Growing evidence suggests that protein lysine methyltransferases (PKMTs) and
      protein arginine methyltransferases (PRMTs) are associated with the development
      of various human diseases, including cancer, inflammation, and psychiatric
      disorders. Given the significant role of these proteins in human disease, efforts
      to discover selective small-molecule inhibitors of these enzymes are quickly
      gaining momentum. In this review, we focus on the recent progress in the
      discovery of selective PKMT and PRMT inhibitors. A future perspective on
      developing methyltransferase inhibitors is also offered.

PMID- 21966349
TI  - Methods for Activity Analysis of the Proteins that Regulate Histone Methylation.
AB  - The enzymes that regulate histone methylation states and the protein domains that
      recognize methylated histone residues have been implicated in a number of human
      diseases, including cancer, as a result of their ability to affect
      transcriptional changes by altering chromatin structure. These proteins are
      recognized as potential therapeutic targets for the treatment of diseases
      associated with epigenetic disruption; however, few inhibitors of their activity
      have been identified. The majority of histone demethylase and methyltransferase
      enzyme inhibitors have been discovered on the basis of their structural
      similarity to substrates or known inhibitors of enzymes with analogous
      mechanisms. The general lack of potency and specificity of these compounds
      indicates that novel chemotypes are needed to address the large number of
      recently discovered histone-modifying enzymes. High-throughput screening (HTS)
      allows rapid testing of chemically diverse small molecule libraries, provided
      assays amenable to HTS exist. Here we review the biochemical and cellular assays
      available for testing the proteins and enzymes that regulate histone methylation.
      Progress in the development of high-throughput, sensitive, and robust assays will
      enable discovery of small molecules for epigenetic therapy.

PMID- 21966350
TI  - Quantitative proteomic approaches to studying histone modifications.
AB  - Histone post-translational modifications (PTMs) positively and negatively
      regulate gene expression, and are consequently a vital influence on the genomic
      profile of all eukaryotic species. The study of histone PTMs using classical
      methods in molecular biology, such as immunofluorescence and Western blotting, is
      challenging given the technical issues of the approaches, and chemical diversity
      and combinatorial patterns of the modifications. In light of these many technical
      limitations, mass spectrometry (MS) is emerging as the most unbiased and rigorous
      experimental platform to identify and quantify histone PTMs in a high-throughput
      manner. This review covers the latest developments in mass spectrometry for the
      analysis of histone PTMs, with the hope of inspiring the continued integration of
      proteomic, genomic and epigenetic research.

PMID- 21966351
TI  - Human papillomavirus (HPV): college male's knowledge, perceived risk, sources of
      information, vaccine barriers and communication.
AB  - BACKGROUND: Human papillomavirus (HPV) is a common sexually transmitted
      infection. With the U.S. Food and Drug Administration (FDA) approval of an
      indication for the HPV vaccine for males, it is important to assess male college
      student's HPV knowledge, perceived risk, and sources of information, as well as
      HPV vaccine barriers and communication.  METHODS: This was a cross-sectional
      survey study of 165 male college students. The participants completed a survey
      about HPV and the HPV vaccine.  RESULTS: Among the 165 participants, most males
      had poor HPV knowledge, in that 132 (80.0%) reported having had sexual
      intercourse, but only 20 (12.1%) perceived being at risk for acquiring HPV.
      Information sources about HPV were commercials/advertisements, friends, news and
      health education programs. Concern about the HPV vaccine's long-term effects and
      cost were the most frequently reported barriers. Most students reported having a
      regular healthcare provider, but had difficulty getting to their provider, and
      finding time to discuss the HPV vaccine with their provider. Additionally, most
      students reported relying on their parents when making medical decisions and
      being willing to discuss the HPV vaccine with their healthcare provider to make
      an informed decision about the vaccine.  CONCLUSIONS: Educational programs
      providing information about HPV, the HPV vaccine, and communication skills
      training are needed for male college students, parents, and healthcare providers.
      Findings from this study will guide the development of HPV vaccine messages and
      educational programs that should be tested in future research.

PMID- 21966352
TI  - Developmental changes in brain function underlying the influence of reward
      processing on inhibitory control.

PMID- 21966353
TI  - Chikungunya virus: evolution and genetic determinants of emergence.
AB  - Chikungunya virus (CHIKV) causes a severe and often persistent arthralgic disease
      that is occasionally fatal. A mosquito-borne virus, CHIKV exists in enzootic, non
      human primate cycles in Africa, but occasionally emerges into urban, human cycles
      to cause major epidemics. Between 1920 and 1950, and again in 2005, CHIKV emerged
      into India and Southeast Asia, where major urban epidemics ensued. Unlike the
      early introduction, the 2005 emergence was accompanied by an adaptive mutation
      that allowed CHIKV to exploit a new epidemic vector, Aedes albopictus, via an
      A226V substitution in the E1 envelope glycoprotein. However, recent reverse
      genetic studies indicate that lineage-specific epistatic restrictions can prevent
      this from exerting its phenotype on mosquito infectivity. Thus, the A. albopictus
      adaptive A226V substitution that is facilitating the dramatic geographic spread
      CHIKV epidemics, was prevented for decades or longer from being selected in most
      African enzootic strains as well as in the older endemic Asian lineage.

PMID- 21966354
TI  - Trends in breast cancer mortality in Sweden before and after implementation of
      mammography screening.
AB  - BACKGROUND: Incidence-based mortality modelling comparing the risk of breast
      cancer death in screened and unscreened women in nine Swedish counties has
      suggested a 39% risk reduction in women 40 to 69 years old after introduction of
      mammography screening in the 1980s and 1990s. OBJECTIVE: We evaluated changes in
      breast cancer mortality in the same nine Swedish counties using a model approach
      based on official Swedish breast cancer mortality statistics, robust to effects
      of over-diagnosis and treatment changes. Using mortality data from the NordCan
      database from 1974 until 2003, we estimated the change in breast cancer mortality
      before and after introduction of mammography screening in at least the 13 years
      that followed screening start. RESULTS: Breast mortality decreased by 16% (95%
      CI: 9 to 22%) in women 40 to 69, and by 11% (95% CI: 2 to 20%) in women 40 to 79
      years of age. DISCUSSION: Without individual data it is impossible to completely
      separate the effects of improved treatment and health service organisation from
      that of screening, which would bias our results in favour of screening. There
      will also be some contamination of post-screening mortality from breast cancer
      diagnosed prior to screening, beyond our attempts to adjust for delayed benefit.
      This would bias against screening. However, our estimates from publicly available
      data suggest considerably lower benefits than estimates based on comparison of
      screened versus non-screened women.

PMID- 21966355
TI  - Oligomeric structure of the MALT1 tandem Ig-like domains.
AB  - BACKGROUND: Mucosa-associated lymphoid tissue 1 (MALT1) plays an important role
      in the adaptive immune program. During TCR- or BCR-induced NF-kappaB activation,
      MALT1 serves to mediate the activation of the IKK (IkappaB kinase) complex, which
      subsequently regulates the activation of NF-kappaB. Aggregation of MALT1 is
      important for E3 ligase activation and NF-kappaB signaling. PRINCIPAL FINDINGS:
      Unlike the isolated CARD or paracaspase domains, which behave as monomers, the
      tandem Ig-like domains of MALT1 exists as a mixture of dimer and tetramer in
      solution. High-resolution structures reveals a protein-protein interface that is
      stabilized by a buried surface area of 1256 A(2) and contains numerous hydrogen
      and salt bonds. In conjunction with a second interface, these interactions may
      represent the basis of MALT1 oligomerization. CONCLUSIONS: The crystal structure
      of the tandem Ig-like domains reveals the oligomerization potential of MALT1 and
      a potential intermediate in the activation of the adaptive inflammatory pathway.
      ENHANCED VERSION: This article can also be viewed as an enhanced version in which
      the text of the article is integrated with interactive 3D representations and
      animated transitions. Please note that a web plugin is required to access this
      enhanced functionality. Instructions for the installation and use of the web
      plugin are available in Text S1.

PMID- 21966356
TI  - Can interferon-gamma or interferon-gamma-induced-protein-10 differentiate
      tuberculosis infection and disease in children of high endemic areas?
AB  - BACKGROUND: Diagnosis of childhood tuberculosis (TB) is difficult in high TB
      burden settings. Interferon-gamma-induced protein 10 (IP10) has been suggested as
      a marker of TB infection and disease, but its ability to differentiate the two
      conditions remains uncertain. OBJECTIVES: To describe Interferon-gamma (INFgamma)
      and IP10 expression in children with TB infection and disease and controls to
      assess their potential to differentiate latent and active TB. METHODS: This was a
      cross sectional study of 322 1-15 years old children with symptoms of TB (28
      confirmed, 136 probable and 131 unlikely TB), 335 children in contact with adults
      with pulmonary TB and 156 community controls in Southern Ethiopia. The Tuberculin
      Skin Test (TST) and Quantiferon-In-Tube (QFT-IT) were performed. INFgamma and
      IP10 were measured in plasma supernatants. RESULTS AND INTERPRETATION: Children
      with confirmed and probable TB and contacts were more likely to have TST+ (78.6%,
      59.3% and 54.1%, respectively) than children with unlikely TB (28.7%) and
      controls (12.8%) (p<0.001). Children with confirmed TB (59.3%) and contacts
      (44.7%) were more likely to have INFgamma+ than children with probable (37.6%) or
      unlikely TB (28.1%) and controls (13.1%) (p<0.001). IP10 concentrations were
      higher in INFgamma+ children independently of TST (p<0.001). There was no
      difference between IP10 concentrations of children with confirmed TB and contacts
      (p = 0.8) and children with and without HIV (p>0.1). INFgamma and IP10 can
      identify children with TB infection and disease, but cannot differentiate between
      the two conditions. HIV status did not affect the expression of IP10.

PMID- 21966357
TI  - Spearfishing regulation benefits artisanal fisheries: the ReGS indicator and its
      application to a multiple-use Mediterranean marine protected area.
AB  - The development of fishing efficiency coupled with an increase of fishing effort
      led to the overexploitation of numerous natural marine resources. In addition to
      this commercial pressure, the impact of recreational activities on fish
      assemblages remains barely known. Here we examined the impact of spearfishing
      limitation on resources in a marine protected area (MPA) and the benefit it
      provides for the local artisanal fishery through the use of a novel indicator. We
      analysed trends in the fish assemblage composition using artisanal fisheries data
      collected in the Bonifacio Strait Natural Reserve (BSNR), a Mediterranean MPA
      where the spearfishing activity has been forbidden over 15% of its area. Fish
      species were pooled into three response groups according to their target level by
      spearfishing. We developed the new flexible ReGS indicator reflecting shifts in
      species assemblages according to the relative abundance of each response group
      facing external pressure. The catch per unit effort (CPUE) increased by ca. 60%
      in the BSNR between 2000 and 2007, while the MPA was established in 1999. The
      gain of CPUE strongly depended on the considered response group: for the highly
      targeted group, the CPUE doubled while the CPUE of the untargeted group increased
      by only 15.5%. The ReGS value significantly increased from 0.31 to 0.45 (on a
      scale between 0 and 1) in the general perimeter of this MPA while it has reached
      a threshold of 0.43, considered as a reference point, in the area protected from
      spearfishing since 1982. Our results demonstrated that limiting recreational
      fishing by appropriate zoning in multiple-use MPAs represents a real benefit for
      artisanal fisheries. More generally we showed how our new indicator may reveal a
      wide range of impacts on coastal ecosystems such as global change or habitat
      degradation.

PMID- 21966358
TI  - Discovery of new molecular subtypes in oesophageal adenocarcinoma.
AB  - A large number of patients suffering from oesophageal adenocarcinomas do not
      respond to conventional chemotherapy; therefore, it is necessary to identify new
      predictive biomarkers and patient signatures to improve patient outcomes and
      therapy selections. We analysed 87 formalin-fixed and paraffin-embedded (FFPE)
      oesophageal adenocarcinoma tissue samples with a reverse phase protein array
      (RPPA) to examine the expression of 17 cancer-related signalling molecules.
      Protein expression levels were analysed by unsupervised hierarchical clustering
      and correlated with clinicopathological parameters and overall patient survival.
      Proteomic analyses revealed a new, very promising molecular subtype of
      oesophageal adenocarcinoma patients characterised by low levels of the HSP27
      family proteins and high expression of those of the HER family with positive
      lymph nodes, distant metastases and short overall survival. After confirmation in
      other independent studies, our results could be the foundation for the
      development of a Her2-targeted treatment option for this new patient subgroup of
      oesophageal adenocarcinoma.

PMID- 21966359
TI  - Reversion of pH-induced physiological drug resistance: a novel function of
      copolymeric nanoparticles.
AB  - AIMS: The extracellular pH of cancer cells is lower than the intracellular pH.
      Weakly basic anticancer drugs will be protonated extracellularly and display a
      decreased intracellular concentration. In this study, we show that copolymeric
      nanoparticles (NPs) are able to overcome this "pH-induced physiological drug
      resistance" (PIPDR) by delivering drugs to the cancer cells via endocytosis
      rather than passive diffussion. MATERIALS AND METHODS: As a model nanoparticle,
      Tetradrine (Tet, Pka 7.80) was incorporated into mPEG-PCL. The effectiveness of
      free Tet and Tet-NPs were compared at different extracellular pHs (pH values 6.8
      and 7.4, respectively) by MTT assay, morphological observation and apoptotic
      analysis in vitro and on a murine model by tumor volume measurement, PET-CT
      scanning and side effect evaluation in vivo. RESULTS: The cytotoxicity of free
      Tet decreased prominently (P<0.05) when the extracellular pH decreased from 7.4
      to 6.8. Meanwhile, the cytotoxicity of Tet-NPs was not significantly influenced
      by reduced pH. In vivo experiment also revealed that Tet-NPs reversed PIPDR more
      effectively than other existing methods and with much less side effects.
      CONCLUSION: The reversion of PIPDR is a new discovered mechanism of copolymeric
      NPs. This study emphasized the importance of cancer microenvironmental factors in
      anticancer drug resistance and revealed the superiority of nanoscale drug carrier
      from a different aspect.

PMID- 21966360
TI  - Enrichment of omnivorous cercozoan nanoflagellates from coastal Baltic Sea
      waters.
AB  - Free-living nano-sized flagellates are important bacterivores in aquatic
      habitats. However, some slightly larger forms can also be omnivorous, i.e.,
      forage upon both bacterial and eukaryotic resources. This hitherto largely
      ignored feeding mode may have pronounced implications for the interpretation of
      experiments about protistan bacterivory. We followed the response of an
      uncultured group of omnivorous cercozoan nanoflagellates from the Novel Clade 2
      (Cerc_BAL02) to experimental food web manipulation in samples from the Gulf of
      Gdansk (Southern Baltic Sea). Seawater was either prefiltered through 5 um
      filters to exclude larger predators of nanoflagellates (F-treatment), or
      prefiltered and subsequently 1?10 diluted with sterile seawater (F+D-treatment)
      to stimulate the growth of both, flagellates and bacteria. Initially, Cerc_BAL02
      were rapidly enriched under both conditions. They foraged on both, eukaryotic
      prey and bacteria, and were highly competitive at low concentrations of food.
      However, these omnivores were later only successful in the F+D treatment, where
      they eventually represented almost one fifth of all aplastidic nanoflagellates.
      By contrast, their numbers stagnated in the F-treatment, possibly due to top-down
      control by a concomitant bloom of other, unidentified flagellates. In analogy
      with observations about the enrichment of opportunistically growing bacteria in
      comparable experimental setups we suggest that the low numbers of omnivorous
      Cerc_Bal02 flagellates in waters of the Gulf of Gdansk might also be related to
      their vulnerability to grazing pressure.

PMID- 21966361
TI  - Copy number and loss of heterozygosity detected by SNP array of formalin-fixed
      tissues using whole-genome amplification.
AB  - The requirement for large amounts of good quality DNA for whole-genome
      applications prohibits their use for small, laser capture micro-dissected (LCM),
      and/or rare clinical samples, which are also often formalin-fixed and paraffin
      embedded (FFPE). Whole-genome amplification of DNA from these samples could,
      potentially, overcome these limitations. However, little is known about the
      artefacts introduced by amplification of FFPE-derived DNA with regard to
      genotyping, and subsequent copy number and loss of heterozygosity (LOH) analyses.
      Using a ligation adaptor amplification method, we present data from a total of 22
      Affymetrix SNP 6.0 experiments, using matched paired amplified and non-amplified
      DNA from 10 LCM FFPE normal and dysplastic oral epithelial tissues, and an
      internal method control. An average of 76.5% of SNPs were called in both matched
      amplified and non-amplified DNA samples, and concordance was a promising 82.4%.
      Paired analysis for copy number, LOH, and both combined, showed that copy number
      changes were reduced in amplified DNA, but were 99.5% concordant when detected,
      amplifications were the changes most likely to be 'missed', only 30% of non
      amplified LOH changes were identified in amplified pairs, and when copy number
      and LOH are combined ~50% of gene changes detected in the unamplified DNA were
      also detected in the amplified DNA and within these changes, 86.5% were
      concordant for both copy number and LOH status. However, there are also changes
      introduced as ~20% of changes in the amplified DNA are not detected in the non
      amplified DNA. An integrative network biology approach revealed that changes in
      amplified DNA of dysplastic oral epithelium localize to topologically critical
      regions of the human protein-protein interaction network, suggesting their
      functional implication in the pathobiology of this disease. Taken together, our
      results support the use of amplification of FFPE-derived DNA, provided sufficient
      samples are used to increase power and compensate for increased error rates.

PMID- 21966362
TI  - Causes of morbidity in wild raptor populations admitted at a wildlife
      rehabilitation centre in Spain from 1995-2007: a long term retrospective study.
AB  - BACKGROUND: Morbidity studies complement the understanding of hazards to raptors
      by identifying natural or anthropogenic factors. Descriptive epidemiological
      studies of wildlife have become an important source of information about hazards
      to wildlife populations. On the other hand, data referenced to the overall wild
      population could provide a more accurate assessment of the potential impact of
      the morbidity/mortality causes in populations of wild birds.
      METHODOLOGY/PRINCIPAL FINDINGS: The present study described the morbidity causes
      of hospitalized wild raptors and their incidence in the wild populations, through
      a long term retrospective study conducted at a wildlife rehabilitation centre of
      Catalonia (1995-2007). Importantly, Seasonal Cumulative Incidences (SCI) were
      calculated considering estimations of the wild population in the region and trend
      analyses were applied among the different years. A total of 7021 birds were
      analysed: 7 species of Strigiformes (n = 3521) and 23 of Falconiformes (n =
      3500). The main causes of morbidity were trauma (49.5%), mostly in the
      Falconiformes, and orphaned/young birds (32.2%) mainly in the Strigiformes.
      During wintering periods, the largest morbidity incidence was observed in
      Accipiter gentillis due to gunshot wounds and in Tyto alba due to vehicle trauma.
      Within the breeding season, Falco tinnunculus (orphaned/young category) and Bubo
      bubo (electrocution and metabolic disorders) represented the most affected
      species. Cases due to orphaned/young, infectious/parasitic diseases,
      electrocution and unknown trauma tended to increase among years. By contrast,
      cases by undetermined cause, vehicle trauma and captivity decreased throughout
      the study period. Interestingly, gunshot injuries remained constant during the
      study period. CONCLUSIONS/SIGNIFICANCE: Frequencies of morbidity causes
      calculated as the proportion of each cause referred to the total number of
      admitted cases, allowed a qualitative assessment of hazards for the studied
      populations. However, cumulative incidences based on estimated wild raptor
      population provided a more accurate approach to the potential ecological impact
      of the morbidity causes in the wild populations.

PMID- 21966363
TI  - D-ribose induces cellular protein glycation and impairs mouse spatial cognition.
AB  - BACKGROUND: D-ribose, an important reducing monosaccharide, is highly active in
      the glycation of proteins, and results in the rapid production of advanced
      glycation end products (AGEs) in vitro. However, whether D-ribose participates in
      glycation and leads to production of AGEs in vivo still requires investigation.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we treated cultured cells and mice with D
      ribose and D-glucose to compare ribosylation and glucosylation for production of
      AGEs. Treatment with D-ribose decreased cell viability and induced more AGE
      accumulation in cells. C57BL/6J mice intraperitoneally injected with D-ribose for
      30 days showed high blood levels of glycated proteins and AGEs. Administration of
      high doses D-ribose also accelerated AGE formation in the mouse brain and induced
      impairment of spatial learning and memory ability according to the performance in
      Morris water maze test. CONCLUSIONS/SIGNIFICANCE: These data demonstrate that D
      ribose but not D-glucose reacts rapidly with proteins and produces significant
      amounts of AGEs in both cultured cells and the mouse brain, leading to
      accumulation of AGEs which may impair mouse spatial cognition.

PMID- 21966364
TI  - Development trends of white matter connectivity in the first years of life.
AB  - The human brain is organized into a collection of interacting networks with
      specialized functions to support various cognitive functions. Recent research has
      reached a consensus that the brain manifests small-world topology, which
      implicates both global and local efficiency at minimal wiring costs, and also
      modular organization, which indicates functional segregation and specialization.
      However, the important questions of how and when the small-world topology and
      modular organization come into existence remain largely unanswered. Taking a
      graph theoretic approach, we attempt to shed light on this matter by an in vivo
      study, using diffusion tensor imaging based fiber tractography, on 39 healthy
      pediatric subjects with longitudinal data collected at average ages of 2 weeks, 1
      year, and 2 years. Our results indicate that the small-world architecture exists
      at birth with efficiency that increases in later stages of development. In
      addition, we found that the networks are broad scale in nature, signifying the
      existence of pivotal connection hubs and resilience of the brain network to
      random and targeted attacks. We also observed, with development, that the brain
      network seems to evolve progressively from a local, predominantly proximity
      based, connectivity pattern to a more distributed, predominantly functional
      based, connectivity pattern. These observations suggest that the brain in the
      early years of life has relatively efficient systems that may solve similar
      information processing problems, but in divergent ways.

PMID- 21966365
TI  - Imaging of zebrafish in vivo with second-harmonic generation reveals shortened
      sarcomeres associated with myopathy induced by statin.
AB  - We employed second-harmonic generation (SHG) imaging and the zebrafish model to
      investigate the myopathy caused by statin in vivo with emphasis on the altered
      microstructures of the muscle sarcomere, the fundamental contractile element of
      muscles. This approach derives an advantage of SHG imaging to observe the
      striated skeletal muscle of living zebrafish based on signals produced mainly
      from the thick myosin filament of sarcomeres without employing exogenous labels,
      and eliminates concern about the distortion of muscle structures caused by sample
      preparation in conventional histological examination. The treatment with statin
      caused a significantly shortened sarcomere relative to an untreated control
      (1.73+/-0.09 um vs 1.91+/-0.08 um, P<0.05) while the morphological integrity of
      the muscle fibers remained largely intact. Mechanistic tests indicated that this
      microstructural disorder was associated with the biosynthetic pathway of
      cholesterol, or, specifically, with the impaired production of mevalonate by
      statins. This microstructural disorder exhibited a strong dependence on both the
      dosage and the duration of treatment, indicating a possibility to assess the
      severity of muscle injury according to the altered length of the sarcomeres. In
      contrast to a conventional assessment of muscle injury using clinical biomarkers
      in blood, such as creatine kinase that is released from only disrupted myocytes,
      the ability to determine microstructural modification of sarcomeres allows
      diagnosis of muscle injury before an onset of conventional clinical symptoms. In
      light of the increasing prevalence of the incidence of muscle injuries caused by
      new therapies, our work consolidates the combined use of the zebrafish and SHG
      imaging as an effective and sensitive means to evaluate the safety profile of new
      therapeutic targets in vivo.

PMID- 21966366
TI  - Destruction of lymphoid organ architecture and hepatitis caused by CD4+ T cells.
AB  - Immune responses have the important function of host defense and protection
      against pathogens. However, the immune response also causes inflammation and host
      tissue injury, termed immunopathology. For example, hepatitis B and C virus
      infection in humans cause immunopathological sequel with destruction of liver
      cells by the host's own immune response. Similarly, after infection with
      lymphocytic choriomeningitis virus (LCMV) in mice, the adaptive immune response
      causes liver cell damage, choriomeningitis and destruction of lymphoid organ
      architecture. The immunopathological sequel during LCMV infection has been
      attributed to cytotoxic CD8(+) T cells. However, we now show that during LCMV
      infection CD4(+) T cells selectively induced the destruction of splenic marginal
      zone and caused liver cell damage with elevated serum alanin-transferase (ALT)
      levels. The destruction of the splenic marginal zone by CD4(+) T cells included
      the reduction of marginal zone B cells, marginal zone macrophages and marginal
      zone metallophilic macrophages. Functionally, this resulted in an impaired
      production of neutralizing antibodies against LCMV. Furthermore, CD4(+) T cells
      reduced B cells with an IgM(high)IgD(low) phenotype (transitional stage 1 and 2,
      marginal zone B cells), whereas other B cell subtypes such as follicular type 1
      and 2 and germinal center/memory B cells were not affected. Adoptive transfer of
      CD4(+) T cells lacking different important effector cytokines and cytolytic
      pathways such as IFNgamma, TNFalpha, perforin and Fas-FasL interaction did reveal
      that these cytolytic pathways are redundant in the induction of
      immunopathological sequel in spleen. In conclusion, our results define an
      important role of CD4(+) T cells in the induction of immunopathology in liver and
      spleen. This includes the CD4(+) T cell mediated destruction of the splenic
      marginal zone with consecutively impaired protective neutralizing antibody
      responses.

PMID- 21966367
TI  - Immune response to Bifidobacterium bifidum strains support Treg/Th17 plasticity.
AB  - In this work we analyzed the immune activation properties of different
      Bifidobacterium strains in order to establish their ability as inductors of
      specific effector (Th) or regulatory (Treg) responses. First, we determined the
      cytokine pattern induced by 21 Bifidobacterium strains in peripheral blood
      mononuclear cells (PBMCs). Results showed that four Bifidobacterium bifidum
      strains showed the highest production of IL-17 as well as a poor secretion of
      IFNgamma and TNFalpha, suggesting a Th17 profile whereas other Bifidobacterium
      strains exhibited a Th1-suggestive profile. Given the key role of Th17 subsets in
      mucosal defence, strains suggestive of Th17 responses and the putative Th1
      Bifidobacterium breve BM12/11 were selected to stimulate dendritic cells (DC) to
      further determine their capability to induce the differentiation of naive CD4(+)
      lymphocytes toward different Th or Treg cells. All selected strains were able to
      induce phenotypic DC maturation, but showed differences in cytokine stimulation,
      DC treated with the putative Th17 strains displaying high IL-1beta/IL-12 and low
      IL-12/IL-10 index, whereas BM12/11-DC exhibited the highest IL-12/IL-10 ratio.
      Differentiation of naive lymphocytes confirmed Th1 polarization by BM12/11.
      Unexpectedly, any B. bifidum strain showed significant capability for Th17
      generation, and they were able to generate functional Treg, thus suggesting
      differences between in vivo and vitro responses. In fact, activation of memory
      lymphocytes present in PBMCS with these bacteria, point out the presence in vivo
      of specific Th17 cells, supporting the plasticity of Treg/Th17 populations and
      the key role of commensal bacteria in mucosal tolerance and T cell reprogramming
      when needed.

PMID- 21966368
TI  - Adipose tissue gene expression of factors related to lipid processing in obesity.
AB  - BACKGROUND: Adipose tissue lipid storage and processing capacity can be a key
      factor for obesity-related metabolic disorders such as insulin resistance and
      diabetes. Lipid uptake is the first step to adipose tissue lipid storage. The aim
      of this study was to analyze the gene expression of factors involved in lipid
      uptake and processing in subcutaneous (SAT) and visceral (VAT) adipose tissue
      according to body mass index (BMI) and the degree of insulin resistance (IR).
      METHODS AND PRINCIPAL FINDINGS: VLDL receptor (VLDLR), lipoprotein lipase (LPL),
      acylation stimulating protein (ASP), LDL receptor-related protein 1 (LRP1) and
      fatty acid binding protein 4 (FABP4) gene expression was measured in VAT and SAT
      from 28 morbidly obese patients with Type 2 Diabetes Mellitus (T2DM) or high IR,
      10 morbidly obese patients with low IR, 10 obese patients with low IR and 12 lean
      healthy controls. LPL, FABP4, LRP1 and ASP expression in VAT was higher in lean
      controls. In SAT, LPL and FABP4 expression were also higher in lean controls.
      BMI, plasma insulin levels and HOMA-IR correlated negatively with LPL expression
      in both VAT and SAT as well as with FABP4 expression in VAT. FABP4 gene
      expression in SAT correlated inversely with BMI and HOMA-IR. However, multiple
      regression analysis showed that BMI was the main variable contributing to LPL and
      FABP4 gene expression in both VAT and SAT. CONCLUSIONS: Morbidly obese patients
      have a lower gene expression of factors related with lipid uptake and processing
      in comparison with healthy lean persons.

PMID- 21966369
TI  - Plexin-B2 negatively regulates macrophage motility, Rac, and Cdc42 activation.
AB  - Plexins are cell surface receptors widely studied in the nervous system, where
      they mediate migration and morphogenesis though the Rho family of small GTPases.
      More recently, plexins have been implicated in immune processes including cell
      cell interaction, immune activation, migration, and cytokine production. Plexin
      B2 facilitates ligand induced cell guidance and migration in the nervous system,
      and induces cytoskeletal changes in overexpression assays through RhoGTPase. The
      function of Plexin-B2 in the immune system is unknown. This report shows that
      Plexin-B2 is highly expressed on cells of the innate immune system in the mouse,
      including macrophages, conventional dendritic cells, and plasmacytoid dendritic
      cells. However, Plexin-B2 does not appear to regulate the production of
      proinflammatory cytokines, phagocytosis of a variety of targets, or directional
      migration towards chemoattractants or extracellular matrix in mouse macrophages.
      Instead, Plxnb2(-/-) macrophages have greater cellular motility than wild type in
      the unstimulated state that is accompanied by more active, GTP-bound Rac and
      Cdc42. Additionally, Plxnb2(-/-) macrophages demonstrate faster in vitro wound
      closure activity. Studies have shown that a closely related family member, Plexin
      B1, binds to active Rac and sequesters it from downstream signaling. The
      interaction of Plexin-B2 with Rac has only been previously confirmed in yeast and
      bacterial overexpression assays. The data presented here show that Plexin-B2
      functions in mouse macrophages as a negative regulator of the GTPases Rac and
      Cdc42 and as a negative regulator of basal cell motility and wound healing.

PMID- 21966370
TI  - Venous graft-derived cells participate in peripheral nerve regeneration.
AB  - BACKGROUND: Based on growing evidence that some adult multipotent cells necessary
      for tissue regeneration reside in the walls of blood vessels and the clinical
      success of vein wrapping for functional repair of nerve damage, we hypothesized
      that the repair of nerves via vein wrapping is mediated by cells migrating from
      the implanted venous grafts into the nerve bundle. METHODOLOGY/PRINCIPAL
      FINDINGS: To test the hypothesis, severed femoral nerves of rats were grafted
      with venous grafts from animals of the opposite sex. Nerve regeneration was
      impaired when decellularized or irradiated venous grafts were used in comparison
      to untreated grafts, supporting the involvement of venous graft-derived cells in
      peripheral nerve repair. Donor cells bearing Y chromosomes integrated into the
      area of the host injured nerve and participated in remyelination and nerve
      regeneration. The regenerated nerve exhibited proper axonal myelination, and
      expressed neuronal and glial cell markers. CONCLUSIONS/SIGNIFICANCE: These novel
      findings identify the mechanism by which vein wrapping promotes nerve
      regeneration.

PMID- 21966371
TI  - Hydrophilic aromatic residue and in silico structure for carbohydrate binding
      module.
AB  - Carbohydrate binding modules (CBMs) are found in polysaccharide-targeting enzymes
      and increase catalytic efficiency. Because only a relatively small number of CBM
      structures have been solved, computational modeling represents an alternative
      approach in conjunction with experimental assessment of CBM functionality and
      ligand-binding properties. An accurate target-template sequence alignment is the
      crucial step during homology modeling. However, low sequence identities between
      target/template sequences can be a major bottleneck. We therefore incorporated
      the predicted hydrophilic aromatic residues (HARs) and secondary structure
      elements into our feature-incorporated alignment (FIA) algorithm to increase CBM
      alignment accuracy. An alignment performance comparison for FIA and six others
      was made, and the greatest average sequence identities and similarities were
      achieved by FIA. In addition, structure models were built for 817 representative
      CBMs. Our models possessed the smallest average surface-potential z scores.
      Besides, a large true positive value for liagnd-binding aromatic residue
      prediction was obtained by HAR identification. Finally, the pre-simulated CBM
      structures have been deposited in the Database of Simulated CBM structures (DS
      CBMs). The web service is publicly available at http://dscbm.life.nthu.edu.tw/
      and http://dscbm.cs.ntou.edu.tw/.

PMID- 21966372
TI  - Incident dementia in a defined older Chinese population.
AB  - BACKGROUND: Current knowledge about incident dementia is mainly derived from
      studies undertaken in the West, showing that dementia is related to older age,
      low socio-economic status, lack of social network, depression and cardiovascular
      disease risk factors. We know little about incidence and predictors of dementia
      in China, where the prevalence is increasing and the patterns of risk factors are
      different. METHODS: Using a standard interview method, we examined 1526 non
      demented people aged >=65 years who had at least minimal educational level in
      China in a 7.5-year follow up. Incident dementia was diagnosed by GMS-AGECAT
      algorithms and psychiatrists. RESULTS: Age-standardised incidence of dementia was
      14.7 per 1000 person-years (95%CI 11.3-18.2 per 1000 person-years). The increased
      risk was significantly associated with age, female gender (adjusted odds ratio
      2.48, 95%CI 1.20-5.13), low educational levels, smoking, angina (2.58, 1.01-6.59)
      and living with fewer family members. Among participants with low educational
      level, the increased risk was associated with higher income, and with the highest
      and lowest occupational classes; adjusted odds ratio 2.74 (95%CI 1.12-6.70) for
      officers/teachers, 3.11 (1.61-6.01) for manual labourers/peasants. CONCLUSIONS:
      Our findings of high incidence of dementia and increased risk among people having
      low education levels but high income suggest a more potential epidemic and burden
      of dementia populations in China. Maintaining social network and activities and
      reducing cardiovascular factors in late life could be integrated into current
      multi-faceted preventive strategies for curbing the epidemic of dementia.

PMID- 21966374
TI  - Comparison of devices used for stent-assisted coiling of intracranial aneurysms.
AB  - INTRODUCTION: Two self-expandable stents, the Neuroform and the Enterprise stent,
      are widely used for stent-assisted coiling (SAC) of complex shaped intracranial
      aneurysms. However, comparative knowledge about technical feasibility, peri- and
      post-procedural morbidity and mortality, packing densities as well as follow-up
      data is limited. MATERIAL AND METHODS: We conducted a retrospective study to
      investigate differences in aneurysms stented with the Enterprise or Neuroform
      stents. Angiographic follow-up (mean 19.42 months) was available in 72.6% (61/84)
      of aneurysms treated with stent-assisted coiling. We further sought to compare
      stent-assisted coiling to a matched patient population with aneurysms treated by
      conventional coil embolization. RESULTS: The stenting success rate of the
      Enterprise was higher compared to the Neuroform stent (46/48 and 42/51,
      respectively). In 5 of 9 cases in which the Neuroform stent was not navigable to
      the landing zone, we successfully deployed an Enterprise stent instead.
      Eventually, 42 aneurysms were coiled after stenting in each group. We observed no
      significant differences in peri-procedural complication rate, post-procedural
      hospital stay, packing density, recurrence rate or number of in-stent stenosis.
      Strikingly, 36.1% of followed aneurysms in the SAC group showed progressive
      occlusion on angiographic follow-up imaging. The packing density was
      significantly higher in aneurysms treated by SAC as compared to conventionally
      coiled aneurysms, while recanalization rate was significantly lower in the SAC
      group. CONCLUSION: The procedural success rate is higher using the Enterprise,
      but otherwise both stents exhibited similar characteristics. Lower recurrence
      frequency and complication rates comparable to conventional coil embolization
      emphasize the importance of stent-assisted coiling in the treatment of complex
      aneurysms. Progressive occlusion on angiographic follow-up was a distinct and
      frequent observation in the SAC group and may in part be due to flow diversion.

PMID- 21966373
TI  - Neuropathology in mice expressing mouse alpha-synuclein.
AB  - alpha-Synuclein (alphaSN) in human is tightly linked both neuropathologically and
      genetically to Parkinson's disease (PD) and related disorders. Disease-causing
      properties in vivo of the wildtype mouse ortholog (malphaSN), which carries a
      threonine at position 53 like the A53T human mutant version that is genetically
      linked to PD, were never reported. To this end we generated mouse lines that
      express malphaSN in central neurons at levels reaching up to six-fold compared to
      endogenous malphaSN. Unlike transgenic mice expressing human wildtype or mutant
      forms of alphaSN, these malphaSN transgenic mice showed pronounced ubiquitin
      immunopathology in spinal cord and brainstem. Isoelectric separation of malphaSN
      species revealed multiple isoforms including two Ser129-phosphorylated species in
      the most severely affected brain regions. Neuronal Ser129-phosphorylated alphaSN
      occurred in granular and small fibrillar aggregates and pathological staining
      patterns in neurites occasionally revealed a striking ladder of small alternating
      segments staining either for Ser129-phosphorylated alphaSN or ubiquitin but not
      both. Axonal degeneration in long white matter tracts of the spinal cord, with
      breakdown of myelin sheaths and degeneration of neuromuscular junctions with loss
      of integrity of the presynaptic neurofilament network in malphaSN transgenic
      mice, was similar to what we have reported for mice expressing human alphaSN
      wildtype or mutant forms. In hippocampal neurons, the malphaSN protein
      accumulated and was phosphorylated but these neurons showed no ubiquitin
      immunopathology. In contrast to the early-onset motor abnormalities and muscle
      weakness observed in mice expressing human alphaSN, malphaSN transgenic mice
      displayed only end-stage phenotypic alterations that manifested alongside with
      neuropathology. Altogether these findings show that increased levels of wildtype
      malphaSN does not induce early-onset behavior changes, but drives end-stage
      pathophysiological changes in murine neurons that are strikingly similar to those
      evoked by expression of human wildtype or mutant forms.

PMID- 21966375
TI  - Changes in gene expression during adaptation of Listeria monocytogenes to the
      soil environment.
AB  - Listeria monocytogenes is a ubiquitous opportunistic pathogen responsible for
      listeriosis. In order to study the processes underlying its ability to adapt to
      the soil environment, whole-genome arrays were used to analyse transcriptome
      modifications 15 minutes, 30 minutes and 18 h after inoculation of L.
      monocytogenes EGD-e in soil extracts. Growth was observed within the first day of
      incubation and large numbers were still detected in soil extract and soil
      microcosms one year after the start of the experiment. Major transcriptional
      reprofiling was observed. Nutrient acquisition mechanisms (phosphoenolpyruvate
      dependent phosphotransferase systems and ABC transporters) and enzymes involved
      in catabolism of specific carbohydrates (beta-glucosidases; chitinases) were
      prevalent. This is consistent with the overrepresentation of the CodY regulon
      that suggests that in a nutrient depleted environment, L. monocytogenes recruits
      its extensive repertoire of transporters to acquire a range of substrates for
      energy production.

PMID- 21966376
TI  - Tracking signals of change in Mediterranean fish diversity based on local
      ecological knowledge.
AB  - One of the expected effects of global change is increased variability in the
      abundance and distribution of living organisms, but information at the
      appropriate temporal and geographical scales is often lacking to observe these
      patterns. Here we use local knowledge as an alternative information source to
      study some emerging changes in Mediterranean fish diversity. A pilot study of
      thirty-two fishermen was conducted in 2009 from four Mediterranean locations
      along a south-north gradient. Semi-quantitative survey information on changes in
      species abundance was recorded by year and suggests that 59 fish species
      belonging to 35 families have experienced changes in their abundance. We
      distinguished species that increased from species that decreased or fluctuated.
      Multivariate analysis revealed significant differences between these three groups
      of species, as well as significant variation between the study locations. A trend
      for thermophilic taxa to increase was recorded at all the study locations. The
      Carangidae and the Sphyraenidae families typically were found to increase over
      time, while Scombridae and Clupeidae were generally identified as decreasing and
      Fistularidae and Scaridae appeared to fluctuate in abundance. Our initial
      findings strongly suggest the northward expansion of termophilic species whose
      occurrence in the northern Mediterranean has only been noted previously by
      occasional records in the scientific literature.

PMID- 21966377
TI  - Reduced expression of transcription factor AP-2alpha is associated with gastric
      adenocarcinoma prognosis.
AB  - BACKGROUND: This study aims to investigate the expression and prognostic
      significance of activator protein 2alpha (AP-2alpha) in gastric adenocarcinoma.
      METHODOLOGY/PRINCIPAL FINDINGS: AP-2alpha expression was analyzed using real-time
      quantitative PCR (RT-qPCR), western blotting, and immunohistochemical staining
      methods on tissue samples from a consecutive series of 481 gastric adenocarcinoma
      patients who underwent resections between 2003 and 2006. The relationship between
      AP-2alpha expression, clinicopathological factors, and patient survival was
      investigated. RT- qPCR results showed that the expression of AP-2alpha mRNA was
      reduced in tumor tissue samples, compared with expression in matched adjacent non
      tumor tissue samples (P = 0.009); this finding was confirmed by western blotting
      analysis (P = 0.012). Immunohistochemical staining data indicated that AP-2alpha
      expression was significantly decreased in 196 of 481 (40.7%) gastric
      adenocarcinoma cases; reduced AP-2alpha expression was also observed in patients
      with poorly differentiated tumors (P = 0.001) and total gastric carcinomas (P =
      0.002), as well as in patients who underwent palliative tumor resection (P =
      0.004). Additionally, reduced expression of AP-2alpha was more commonly observed
      in tumors that were staged as T4a/b (P = 0.018), N3 (P = 0.006), and M1 (P =
      0.008). Kaplan-Meier survival curves revealed that reduced expression of AP
      2alpha was associated with poor prognosis in gastric adenocarcinoma patients
      (P<0.001). Multivariate Cox analysis identified AP-2alpha expression as an
      independent prognostic factor for overall survival (HR = 1.512, 95% CI = 1.127
      2.029, P = 0.006). CONCLUSIONS/SIGNIFICANCE: Our data suggest that AP-2alpha
      plays an important role in tumor progression and that reduced AP-2alpha
      expression independently predicts an unfavorable prognosis in gastric
      adenocarcinoma patients.

PMID- 21966378
TI  - Functional mapping of dynamic traits with robust t-distribution.
AB  - Functional mapping has been a powerful tool in mapping quantitative trait loci
      (QTL) underlying dynamic traits of agricultural or biomedical interest. In
      functional mapping, multivariate normality is often assumed for the underlying
      data distribution, partially due to the ease of parameter estimation. The
      normality assumption however could be easily violated in real applications due to
      various reasons such as heavy tails or extreme observations. Departure from
      normality has negative effect on testing power and inference for QTL
      identification. In this work, we relax the normality assumption and propose a
      robust multivariate t-distribution mapping framework for QTL identification in
      functional mapping. Simulation studies show increased mapping power and precision
      with the t distribution than that of a normal distribution. The utility of the
      method is demonstrated through a real data analysis.

PMID- 21966379
TI  - Early lung function testing in infants with aortic arch anomalies identifies
      patients at risk for airway obstruction.
AB  - BACKGROUND: Aortic arch anomalies (AAA) are rare cardio-vascular anomalies. Right
      sided and double-sided aortic arch anomalies (RAAA, DAAA) are distinguished, both
      may cause airway obstructions. We studied the degree of airway obstruction in
      infants with AAA by neonatal lung function testing (LFT). PATIENTS AND METHODS:
      17 patients (10 RAAA and 7 DAAA) with prenatal diagnosis of AAA were
      investigated. The median (range) post conception age at LFT was 40.3 (36.6-44.1)
      weeks, median body weight 3400 (2320-4665) g. Measurements included tidal
      breathing flow-volume loops (TBFVL), airway resistance (R(aw)) by
      bodyplethysmography and the maximal expiratory flow at functional residual
      capacity (V'(max)FRC) by rapid thoracic-abdominal compression (RTC) technique.
      V'(max)FRC was also expressed in Z-scores, based on published gender-, age and
      height-specific reference values. RESULTS: Abnormal lung function tests were seen
      in both RAAA and DAAA infants. Compared to RAAA infants, infants with DAAA had
      significantly more expiratory flow limitations in the TBFVL, (86% vs. 30%,
      p<0.05) and a significantly increased R(aw) (p = 0.015). Despite a significant
      correlation between R(aw) and the Z-score of V'(max)FRC (r = 0.740, p<0.001),
      there were no statistically significant differences in V'(max)FRC and it's Z
      scores between RAAA and DAAA infants. 4 (24%) infants (2 RAAA, 2 DAAA) were near
      or below the 10(th) percentile of V'(max)FRC, indicating a high risk for airway
      obstruction. CONCLUSION: Both, infants with RAAA and DAAA, are at risk for airway
      obstruction and early LFT helps to identify and to monitor these infants. This
      may support the decision for therapeutic interventions before clinical symptoms
      arise.

PMID- 21966380
TI  - Microarray generation of thousand-member oligonucleotide libraries.
AB  - The ability to efficiently and economically generate libraries of defined pieces
      of DNA would have a myriad of applications, not least in the area of defined or
      directed sequencing and synthetic biology, but also in applications associated
      with encoding and tagging. In this manuscript DNA microarrays were used to allow
      the linear amplification of immobilized DNA sequences from the array followed by
      PCR amplification. Arrays of increasing sophistication (1, 10, 3,875, 10,000
      defined sequences) were used to validate the process, with sequences verified by
      selective hybridization to a complementary DNA microarray and DNA sequencing,
      which demonstrated a PCR error rate of 9.7*10(-3)/site/duplication. This
      technique offers an economical and efficient way of producing specific DNA
      libraries of hundreds to thousands of members with the DNA-arrays being used as
      "factories" allowing specific DNA oligonucleotide pools to be generated. We also
      found substantial variance observed between the sequence frequencies found via
      Solexa sequencing and microarray analysis, highlighting the care needed in the
      interpretation of profiling data.

PMID- 21966381
TI  - Genetic heterogeneity of hepatitis C virus in association with antiviral therapy
      determined by ultra-deep sequencing.
AB  - BACKGROUND AND AIMS: The hepatitis C virus (HCV) invariably shows wide
      heterogeneity in infected patients, referred to as a quasispecies population.
      Massive amounts of genetic information due to the abundance of HCV variants could
      be an obstacle to evaluate the viral genetic heterogeneity in detail. METHODS:
      Using a newly developed massive-parallel ultra-deep sequencing technique, we
      investigated the viral genetic heterogeneity in 27 chronic hepatitis C patients
      receiving peg-interferon (IFN) alpha2b plus ribavirin therapy. RESULTS: Ultra
      deep sequencing determined a total of more than 10 million nucleotides of the HCV
      genome, corresponding to a mean of more than 1000 clones in each specimen, and
      unveiled extremely high genetic heterogeneity in the genotype 1b HCV population.
      There was no significant difference in the level of viral complexity between
      immediate virologic responders and non-responders at baseline (p = 0.39).
      Immediate virologic responders (n = 8) showed a significant reduction in the
      genetic complexity spanning all the viral genetic regions at the early phase of
      IFN administration (p = 0.037). In contrast, non-virologic responders (n = 8)
      showed no significant changes in the level of viral quasispecies (p = 0.12),
      indicating that very few viral clones are sensitive to IFN treatment. We also
      demonstrated that clones resistant to direct-acting antivirals for HCV, such as
      viral protease and polymerase inhibitors, preexist with various abundances in all
      27 treatment-naive patients, suggesting the risk of the development of drug
      resistance against these agents. CONCLUSION: Use of the ultra-deep sequencing
      technology revealed massive genetic heterogeneity of HCV, which has important
      implications regarding the treatment response and outcome of antiviral therapy.

PMID- 21966383
TI  - Persistence and availability of Web services in computational biology.
AB  - We have conducted a study on the long-term availability of bioinformatics Web
      services: an observation of 927 Web services published in the annual Nucleic
      Acids Research Web Server Issues between 2003 and 2009. We found that 72% of Web
      sites are still available at the published addresses, only 9% of services are
      completely unavailable. Older addresses often redirect to new pages. We checked
      the functionality of all available services: for 33%, we could not test
      functionality because there was no example data or a related problem; 13% were
      truly no longer working as expected; we could positively confirm functionality
      only for 45% of all services. Additionally, we conducted a survey among 872 Web
      Server Issue corresponding authors; 274 replied. 78% of all respondents indicate
      their services have been developed solely by students and researchers without a
      permanent position. Consequently, these services are in danger of falling into
      disrepair after the original developers move to another institution, and indeed,
      for 24% of services, there is no plan for maintenance, according to the
      respondents. We introduce a Web service quality scoring system that correlates
      with the number of citations: services with a high score are cited 1.8 times more
      often than low-scoring services. We have identified key characteristics that are
      predictive of a service's survival, providing reviewers, editors, and Web service
      developers with the means to assess or improve Web services. A Web service
      conforming to these criteria receives more citations and provides more reliable
      service for its users. The most effective way of ensuring continued access to a
      service is a persistent Web address, offered either by the publishing journal, or
      created on the authors' own initiative, for example at http://bioweb.me. The
      community would benefit the most from a policy requiring any source code needed
      to reproduce results to be deposited in a public repository.

PMID- 21966382
TI  - The molecular assembly of amyloid abeta controls its neurotoxicity and binding to
      cellular proteins.
AB  - Accumulation of beta-sheet-rich peptide (Abeta) is strongly associated with
      Alzheimer's disease, characterized by reduction in synapse density, structural
      alterations of dendritic spines, modification of synaptic protein expression,
      loss of long-term potentiation and neuronal cell death. Abeta species are potent
      neurotoxins, however the molecular mechanism responsible for Abeta toxicity is
      still unknown. Numerous mechanisms of toxicity were proposed, although there is
      no agreement about their relative importance in disease pathogenesis. Here, the
      toxicity of Abeta 1-40 and Abeta 1-42 monomers, oligomers or fibrils, was
      evaluated using the N2a cell line. A structure-function relationship between
      peptide aggregation state and toxic properties was established. Moreover, we
      demonstrated that Abeta toxic species cross the plasma membrane, accumulate in
      cells and bind to a variety of internal proteins, especially on the cytoskeleton
      and in the endoplasmatic reticulum (ER). Based on these data we suggest that
      numerous proteins act as Abeta receptors in N2a cells, triggering a multi
      factorial toxicity.

PMID- 21966384
TI  - The A-current modulates learning via NMDA receptors containing the NR2B subunit.
AB  - Synaptic plasticity involves short- and long-term events, although the molecular
      mechanisms that underlie these processes are not fully understood. The transient
      A-type K(+) current (I(A)) controls the excitability of the dendrites from CA1
      pyramidal neurons by regulating the back-propagation of action potentials and
      shaping synaptic input. Here, we have studied how decreases in I(A) affect
      cognitive processes and synaptic plasticity. Using wild-type mice treated with 4
      AP, an I(A) inhibitor, and mice lacking the DREAM protein, a transcriptional
      repressor and modulator of the I(A), we demonstrate that impairment of I(A)
      decreases the stimulation threshold for learning and the induction of early-LTP.
      Hippocampal electrical recordings in both models revealed alterations in basal
      electrical oscillatory properties toward low-theta frequencies. In addition, we
      demonstrated that the facilitated learning induced by decreased I(A) requires the
      activation of NMDA receptors containing the NR2B subunit. Together, these
      findings point to a balance between the I(A) and the activity of NR2B-containing
      NMDA receptors in the regulation of learning.

PMID- 21966385
TI  - Cryopreservation of spin-dried mammalian cells.
AB  - This study reports an alternative approach to achieve vitrification where cells
      are pre-desiccated prior to cooling to cryogenic temperatures for storage.
      Chinese Hamster Ovary (CHO) cells suspended in a trehalose solution were rapidly
      and uniformly desiccated to a low moisture content (<0.12 g of water per g of dry
      weight) using a spin-drying technique. Trehalose was also introduced into the
      cells using a high-capacity trehalose transporter (TRET1). Fourier Transform
      Infrared Spectroscopy (FTIR) was used to examine the uniformity of water
      concentration distribution in the spin-dried samples. 62% of the cells were shown
      to survive spin-drying in the presence of trehalose following immediate
      rehydration. The spin-dried samples were stored in liquid nitrogen (LN(2)) at a
      vitrified state. It was shown that following re-warming to room temperature and
      re-hydration with a fully complemented cell culture medium, 51% of the spin-dried
      and vitrified cells survived and demonstrated normal growth characteristics. Spin
      drying is a novel strategy that can be used to improve cryopreservation outcome
      by promoting rapid vitrification.

PMID- 21966386
TI  - Mitral cells of the olfactory bulb perform metabolic sensing and are disrupted by
      obesity at the level of the Kv1.3 ion channel.
AB  - Sixty-five percent of Americans are over-weight. While the neuroendocrine
      controls of energy homeostasis are well known, how sensory systems respond to and
      are impacted by obesity is scantily understood. The main accepted function of the
      olfactory system is to provide an internal depiction of our external chemical
      environment, starting from the detection of chemosensory cues. We hypothesized
      that the system additionally functions to encode internal chemistry via the
      detection of chemicals that are important indicators of metabolic state. We here
      uncovered that the olfactory bulb (OB) subserves as an internal sensor of
      metabolism via insulin-induced modulation of the potassium channel Kv1.3. Using
      an adult slice preparation of the olfactory bulb, we found that evoked neural
      activity in Kv1.3-expressing mitral cells is enhanced following acute insulin
      application. Insulin mediated changes in mitral cell excitability are
      predominantly due to the modulation of Kv1.3 channels as evidenced by the lack of
      effect in slices from Kv1.3-null mice. Moreover, a selective Kv1.3 peptide
      blocker (ShK186) inhibits more than 80% of the outward current in parallel
      voltage-clamp studies, whereby insulin significantly decreases the peak current
      magnitude without altering the kinetics of inactivation or deactivation. Mice
      that were chronically administered insulin using intranasal delivery approaches
      exhibited either an elevation in basal firing frequency or fired a single cluster
      of action potentials. Following chronic administration of the hormone, mitral
      cells were inhibited by application of acute insulin rather than excited. Mice
      made obese through a diet of ~32% fat exhibited prominent changes in mitral cell
      action potential shape and clustering behavior, whereby the subsequent response
      to acute insulin stimulation was either attenuated or completely absent. Our
      results implicate an inappropriate neural function of olfactory sensors following
      exposure to chronic levels of the hormone insulin (diabetes) or increased body
      weight (obesity).

PMID- 21966387
TI  - Characterizing and modeling citation dynamics.
AB  - Citation distributions are crucial for the analysis and modeling of the activity
      of scientists. We investigated bibliometric data of papers published in journals
      of the American Physical Society, searching for the type of function which best
      describes the observed citation distributions. We used the goodness of fit with
      Kolmogorov-Smirnov statistics for three classes of functions: log-normal, simple
      power law and shifted power law. The shifted power law turns out to be the most
      reliable hypothesis for all citation networks we derived, which correspond to
      different time spans. We find that citation dynamics is characterized by bursts,
      usually occurring within a few years since publication of a paper, and the burst
      size spans several orders of magnitude. We also investigated the microscopic
      mechanisms for the evolution of citation networks, by proposing a linear
      preferential attachment with time dependent initial attractiveness. The model
      successfully reproduces the empirical citation distributions and accounts for the
      presence of citation bursts as well.

PMID- 21966388
TI  - Dynamics of dynamics within a single data acquisition session: variation in
      neocortical alpha oscillations in human MEG.
AB  - BACKGROUND: Behavioral paradigms applied during human recordings in electro- and
      magneto- encephalography (EEG and MEG) typically require 1-2 hours of data
      collection. Over this time scale, the natural fluctuations in brain state or
      rapid learning effects could impact measured signals, but are seldom analyzed.
      METHODS AND FINDINGS: We investigated within-session dynamics of neocortical
      alpha (7-14 Hz) rhythms and their allocation with cued-attention using MEG
      recorded from primary somatosensory neocortex (SI) in humans. We found that there
      were significant and systematic changes across a single ~1 hour recording session
      in several dimensions, including increased alpha power, increased differentiation
      in attention-induced alpha allocation, increased distinction in immediate time
      locked post-cue evoked responses in SI to different visual cues, and enhanced
      power in the immediate cue-locked alpha band frequency response. Further,
      comparison of two commonly used baseline methods showed that conclusions on the
      evolution of alpha dynamics across a session were dependent on the normalization
      method used. CONCLUSIONS: These findings are important not only as they relate to
      studies of oscillations in SI, they also provide a robust example of the type of
      dynamic changes in brain measures within a single session that are overlooked in
      most human brain imaging/recording studies.

PMID- 21966389
TI  - IL-4 amplifies the pro-inflammatory effect of adenosine in human mast cells by
      changing expression levels of adenosine receptors.
AB  - Adenosine inhalation produces immediate bronchoconstriction in asthmatics but not
      in normal subjects. The bronchospastic effect of adenosine is largely mediated
      through adenosine-induced mast cell activation, the mechanism of which is poorly
      understood due to limitations in culturing human primary mast cells. Here, we
      show that human umbilical cord blood -derived mast cells incubated with the Th2
      cytokine IL-4 develop increased sensitivity to adenosine. Potentiation of anti
      IgE- induced and calcium ionophore/PMA-induced degranulation was augmented in
      mast cells cultured with IL-4, and this effect was reduced or abolished by pre
      treatment with A(2B)siRNA and selective A(2B) receptor antagonists, respectively.
      IL-4 incubation resulted in the increased expression of A(2B) and reduced
      expression of A(2A) adenosine receptors on human mast cells. These results
      suggest that Th2 cytokines in the asthmatic lung may alter adenosine receptor
      expression on airway mast cells to promote increased responsiveness to adenosine.

PMID- 21966391
TI  - Overexpression of cathepsin Z contributes to tumor metastasis by inducing
      epithelial-mesenchymal transition in hepatocellular carcinoma.
AB  - The aim of this study was to characterize the oncogenic function and mechanism of
      Cathepsin Z (CTSZ) at 20q13.3, a frequently amplified region in hepatocellular
      carcinoma (HCC). Real-time PCR were used to compare CTSZ expression between
      paired HCC tumor and non-tumor specimens. CTSZ gene was stably transfected into
      HCC line QGY-7703 cells and its role in tumorigenicity and cell motility was
      characterized by soft agar, wound-healing, transwell invasion and cell adhesion
      assay, and tumor xenograft mouse model. Western blot analysis was used to study
      expression of proteins associated with epithelial-mesenchymal transition
      (EMT).Upregulation of CTSZ was detected in 59/137 (43%) of primary HCCs, which
      was significantly associated with advanced clinical stage (P = 0.000). Functional
      study found that CTSZ could increase colony formation in soft agar and promote
      cell motility. Further study found that the metastatic effect of CTSZ was
      associated with its role in inducing epithelial-mesenchymal transition (EMT) by
      upregulating mesenchymal markers (fibronectin and vimentin) and downregulating
      epithelial markers (E-cadherin and alpha-catenin). In addition, CTSZ could also
      upregulate proteins associated with extracellular matrix remodeling such as MMP2,
      MMP3 and MMP9. Taken together, our data suggested that CTSZ was a candidate
      oncogene within the 20q13 amplicon and it played an important role in HCC
      metastasis.

PMID- 21966390
TI  - Effects of the histone deacetylase inhibitor valproic acid on human pericytes in
      vitro.
AB  - Microvascular pericytes are of key importance in neoformation of blood vessels,
      in stabilization of newly formed vessels as well as maintenance of angiostasis in
      resting tissues. Furthermore, pericytes are capable of differentiating into pro
      fibrotic collagen type I producing fibroblasts. The present study investigates
      the effects of the histone deacetylase (HDAC) inhibitor valproic acid (VPA) on
      pericyte proliferation, cell viability, migration and differentiation. The
      results show that HDAC inhibition through exposure of pericytes to VPA in vitro
      causes the inhibition of pericyte proliferation and migration with no effect on
      cell viability. Pericyte exposure to the potent HDAC inhibitor Trichostatin A
      caused similar effects on pericyte proliferation, migration and cell viability.
      HDAC inhibition also inhibited pericyte differentiation into collagen type I
      producing fibroblasts. Given the importance of pericytes in blood vessel biology
      a qPCR array focusing on the expression of mRNAs coding for proteins that
      regulate angiogenesis was performed. The results showed that HDAC inhibition
      promoted transcription of genes involved in vessel stabilization/maturation in
      human microvascular pericytes. The present in vitro study demonstrates that VPA
      influences several aspects of microvascular pericyte biology and suggests an
      alternative mechanism by which HDAC inhibition affects blood vessels. The results
      raise the possibility that HDAC inhibition inhibits angiogenesis partly through
      promoting a pericyte phenotype associated with stabilization/maturation of blood
      vessels.

PMID- 21966392
TI  - The effects of age, exposure history and malaria infection on the susceptibility
      of Anopheles mosquitoes to low concentrations of pyrethroid.
AB  - Chemical insecticides are critical components of malaria control programs. Their
      ability to eliminate huge numbers of mosquitoes allows them to swiftly interrupt
      disease transmission, but that lethality also imposes immense selection for
      insecticide resistance. Targeting control at the small portion of the mosquito
      population actually responsible for transmitting malaria parasites to humans
      would reduce selection for resistance, yet maintain effective malaria control.
      Here, we ask whether simply lowering the concentration of the active ingredient
      in insecticide formulations could preferentially kill mosquitoes infected with
      malaria and/or those that are potentially infectious, namely, old mosquitoes.
      Using modified WHO resistance-monitoring assays, we exposed uninfected Anopheles
      stephensi females to low concentrations of the pyrethroid permethrin at days 4,
      8, 12, and 16 days post-emergence and monitored survival for at least 30 days to
      evaluate the immediate and long-term effects of repeated exposure as mosquitoes
      aged. We also exposed Plasmodium chabaudi- and P. yoelii-infected An. stephensi
      females. Permethrin exposure did not consistently increase mosquito
      susceptibility to subsequent insecticide exposure, though older mosquitoes were
      more susceptible. A blood meal slightly improved survival after insecticide
      exposure; malaria infection did not detectably increase insecticide
      susceptibility. Exposure to low concentrations over successive feeding cycles
      substantially altered cohort age-structure. Our data suggest the possibility
      that, where high insecticide coverage can be achieved, low concentration
      formulations have the capacity to reduce disease transmission without the massive
      selection for resistance imposed by current practice.

PMID- 21966393
TI  - No effect of folic acid supplementation on global DNA methylation in men and
      women with moderately elevated homocysteine.
AB  - A global loss of cytosine methylation in DNA has been implicated in a wide range
      of diseases. There is growing evidence that modifications in DNA methylation can
      be brought about by altering the intake of methyl donors such as folate. We
      examined whether long-term daily supplementation with 0.8 mg of folic acid would
      increase global DNA methylation compared with placebo in individuals with
      elevated plasma homocysteine. We also investigated if these effects were modified
      by MTHFR C677T genotype. Two hundred sixteen participants out of 818 subjects who
      had participated in a randomized double-blind placebo-controlled trial were
      selected, pre-stratified on MTHFR C677T genotype and matched on age and smoking
      status. They were allocated to receive either folic acid (0.8 mg/d; n = 105) or
      placebo treatment (n = 111) for three years. Peripheral blood leukocyte DNA
      methylation and serum and erythrocyte folate were assessed. Global DNA
      methylation was measured using liquid chromatography-tandem mass spectrometry and
      expressed as a percentage of 5-methylcytosines versus the total number of
      cytosine. There was no difference in global DNA methylation between those
      randomized to folic acid and those in the placebo group (difference = 0.008,
      95%CI = -0.05,0.07, P = 0.79). There was also no difference between treatment
      groups when we stratified for MTHFR C677T genotype (CC, n = 76; CT, n = 70; TT, n
      = 70), baseline erythrocyte folate status or baseline DNA methylation levels. In
      moderately hyperhomocysteinemic men and women, long-term folic acid
      supplementation does not increase global DNA methylation in peripheral blood
      leukocytes.ClinicalTrials.gov NCT00110604.

PMID- 21966394
TI  - Galphai2- and Galphai3-specific regulation of voltage-dependent L-type calcium
      channels in cardiomyocytes.
AB  - BACKGROUND: Two pertussis toxin sensitive G(i) proteins, G(i2) and G(i3), are
      expressed in cardiomyocytes and upregulated in heart failure. It has been
      proposed that the highly homologous G(i) isoforms are functionally distinct. To
      test for isoform-specific functions of G(i) proteins, we examined their role in
      the regulation of cardiac L-type voltage-dependent calcium channels (L-VDCC).
      METHODS: Ventricular tissues and isolated myocytes were obtained from mice with
      targeted deletion of either Galpha(i2) (Galpha(i2) (-/-)) or Galpha(i3)
      (Galpha(i3) (-/-)). mRNA levels of Galpha(i/o) isoforms and L-VDCC subunits were
      quantified by real-time PCR. Galpha(i) and Ca(v)alpha(1) protein levels as well
      as protein kinase B/Akt and extracellular signal-regulated kinases 1/2 (ERK1/2)
      phosphorylation levels were assessed by immunoblot analysis. L-VDCC function was
      assessed by whole-cell and single-channel current recordings. RESULTS: In cardiac
      tissue from Galpha(i2) (-/-) mice, Galpha(i3) mRNA and protein expression was
      upregulated to 187 +/- 21% and 567 +/- 59%, respectively. In Galpha(i3) (-/-)
      mouse hearts, Galpha(i2) mRNA (127 +/- 5%) and protein (131 +/- 10%) levels were
      slightly enhanced. Interestingly, L-VDCC current density in cardiomyocytes from
      Galpha(i2) (-/-) mice was lowered (-7.9 +/- 0.6 pA/pF, n = 11, p<0.05) compared
      to wild-type cells (-10.7 +/- 0.5 pA/pF, n = 22), whereas it was increased in
      myocytes from Galpha(i3) (-/-) mice (-14.3 +/- 0.8 pA/pF, n = 14, p<0.05). Steady
      state inactivation was shifted to negative potentials, and recovery kinetics
      slowed in the absence of Galpha(i2) (but not of Galpha(i3)) and following
      treatment with pertussis toxin in Galpha(i3) (-/-). The pore forming
      Ca(v)alpha(1) protein level was unchanged in all mouse models analyzed, similar
      to mRNA levels of Ca(v)alpha(1) and Ca(v)beta(2) subunits. Interestingly, at the
      cellular signalling level, phosphorylation assays revealed abolished carbachol
      triggered activation of ERK1/2 in mice lacking Galpha(i2). CONCLUSION: Our data
      provide novel evidence for an isoform-specific modulation of L-VDCC by Galpha(i)
      proteins. In particular, loss of Galpha(i2) is reflected by alterations in
      channel kinetics and likely involves an impairment of the ERK1/2 signalling
      pathway.

PMID- 21966395
TI  - Circulating soluble endoglin levels in pregnant women in Cameroon and Malawi-
      associations with placental malaria and fetal growth restriction.
AB  - Placental infections with Plasmodium falciparum are associated with fetal growth
      restriction resulting in low birth weight (LBW). The mechanisms that mediate
      these effects have yet to be completely described; however, they are likely to
      involve inflammatory processes and dysregulation of angiogenesis. Soluble
      endoglin (sEng), a soluble receptor of transforming growth factor (TGF)-beta
      previously associated with preeclampsia in pregnant women and with severe malaria
      in children, regulates the immune system and influences angiogenesis. We
      hypothesized that sEng may play a role in development of LBW associated with
      placental malaria (PM). Plasma levels of sEng were measured in women (i) followed
      prospectively throughout pregnancy in Cameroon (n = 52), and (ii) in a case
      control study at delivery in Malawi (n = 479). The relationships between sEng
      levels and gravidity, peripheral and placental parasitemia, gestational age, and
      adverse outcomes of PM including maternal anemia and LBW were determined. In the
      longitudinal cohort from Cameroon, 28 of 52 women (54%) experienced at least one
      malaria infection during pregnancy. In Malawi we enrolled two aparasitemic
      gravidity-matched controls for every case with PM. sEng levels varied over the
      course of gestation and were significantly higher in early and late gestation as
      compared to delivery (P<0.006 and P<0.0001, respectively). Circulating sEng
      levels were higher in primigravidae than multigravidae from both Cameroon and
      Malawi, irrespective of malarial infection status (p<0.046 and p<0.001,
      respectively). Peripheral parasitemia in Cameroonian women and PM in Malawian
      women were each associated with elevated sEng levels following correction for
      gestational age and gravidity (p = 0.006 and p = 0.033, respectively). Increased
      sEng was also associated with the delivery of LBW infants in primigravid Malawian
      women (p = 0.017); the association was with fetal growth restriction (p = 0.003)
      but not pre-term delivery (p = 0.286). Increased circulating maternal sEng levels
      are associated with P. falciparum infection in pregnancy and with fetal growth
      restriction in primigravidae with PM.

PMID- 21966396
TI  - Comparative genomics study of multi-drug-resistance mechanisms in the antibiotic
      resistant Streptococcus suis R61 strain.
AB  - BACKGROUND: Streptococcus suis infections are a serious problem for both humans
      and pigs worldwide. The emergence and increasing prevalence of antibiotic
      resistant S. suis strains pose significant clinical and societal challenges.
      RESULTS: In our study, we sequenced one multi-drug-resistant S. suis strain, R61,
      and one S. suis strain, A7, which is fully sensitive to all tested antibiotics.
      Comparative genomic analysis revealed that the R61 strain is phylogenetically
      distinct from other S. suis strains, and the genome of R61 exhibits extreme
      levels of evolutionary plasticity with high levels of gene gain and loss. Our
      results indicate that the multi-drug-resistant strain R61 has evolved three main
      categories of resistance. CONCLUSIONS: Comparative genomic analysis of S. suis
      strains with diverse drug-resistant phenotypes provided evidence that horizontal
      gene transfer is an important evolutionary force in shaping the genome of multi
      drug-resistant strain R61. In this study, we discovered novel and previously
      unexamined mutations that are strong candidates for conferring drug resistance.
      We believe that these mutations will provide crucial clues for designing new
      drugs against this pathogen. In addition, our work provides a clear demonstration
      that the use of drugs has driven the emergence of the multi-drug-resistant strain
      R61.

PMID- 21966397
TI  - Detecting one-hundred-year environmental changes in Western China using seven
      year repeat photography.
AB  - Due to its diverse, wondrous plants and unique topography, Western China has
      drawn great attention from explorers and naturalists from the Western World.
      Among them, Ernest Henry Wilson (1876 -1930), known as 'Chinese' Wilson,
      travelled to Western China five times from 1899 to 1918. He took more than 1,000
      photos during his travels. These valuable photos illustrated the natural and
      social environment of Western China a century ago. Since 1997, we had collected
      E.H. Wilson's old pictures, and then since 2004, along the expedition route of
      E.H. Wilson, we took 7 years to repeat photographing 250 of these old pictures.
      Comparing Wilson's photos with ours, we found an obvious warming trend over the
      100 years, not only in specific areas but throughout the entire Western China.
      Such warming trend manifested in phenology changes, community shifts and melting
      snow in alpine mountains. In this study, we also noted remarkable vegetation
      changes. Out of 62 picture pairs were related to vegetation change, 39 indicated
      vegetation has changed to the better condition, 17 for degraded vegetation and
      six for no obvious change. Also in these photos at a century interval, we found
      not only rapid urbanization in Western China, but also the disappearance of
      traditional cultures. Through such comparisons, we should not only be amazed
      about the significant environmental changes through time in Western China, but
      also consider its implications for protecting environment while meeting the
      economic development beyond such changes.

PMID- 21966398
TI  - Quantitative ColourDopplerSonography evaluation of cerebral venous outflow: a
      comparative study between patients with multiple sclerosis and controls.
AB  - BACKGROUND: Internal Jugular Veins (IJVs) are the principle outflow pathway for
      intracranial blood in clinostatism condition. In the seated position, IJVs
      collapse, while Vertebral Veins (VVs) increase the venous outflow and partially
      compensate the venous drainage. Spinal Epidural Veins are an additional drainage
      pathway in the seated position. Colour- Doppler-Sonography (CDS) examination is
      able to demonstrate IJVs and VVs outflow in different postural and respiratory
      conditions. The purpose of this study was to evaluate CDS quantification of the
      cerebral venous outflow (CVF) in healthy subjects and patients with multiple
      sclerosis (MS). METHODOLOGY/PRINCIPAL FINDINGS: In a group of 27 healthy adults
      (13 females and 14 males; mean age 37.8 +/- 11.2 years), and 52 patients with MS
      (32 females and 20 males; mean age 42.6 +/- 12.1 years), CVF has been measured in
      clinostatism and in the seated position as the sum of the flow in IJVs and VVs.
      The difference between CVF in clinostatism and CVF in the seated position
      (DeltaCVF) has been correlated with patients' status (healthy or MS), and a
      number of clinical variables in MS patients. Statistical analysis was performed
      by Fisher's exact test, non-parametric Mann-Whitney U test, ANOVA Kruskal-Wallis
      test, and correntropy coefficient. The value of DeltaCVF was negative in 59.6% of
      patients with MS and positive in 96.3% of healthy subjects. Negative DeltaCVF
      values were significantly associated with MS (p<0.0001). There was no significant
      correlation with clinical variables. CONCLUSIONS/SIGNIFICANCE: Negative DeltaCVF
      has a hemodynamic significance, since it reflects an increased venous return in
      the seated position. This seems to be a pathologic condition. In MS patients, a
      vascular dysregulation resulting from involvement of the autonomous nervous
      system may be supposed. DeltaCVF value should be included in the quantitative CDS
      evaluation of the cerebral venous drainage, in order to identify cerebral venous
      return abnormalities.

PMID- 21966399
TI  - Meningitic Escherichia coli K1 penetration and neutrophil transmigration across
      the blood-brain barrier are modulated by alpha7 nicotinic receptor.
AB  - Alpha7 nicotinic acetylcholine receptor (nAChR), an essential regulator of
      inflammation, is abundantly expressed in hippocampal neurons, which are
      vulnerable to bacterial meningitis. However, it is unknown whether alpha7 nAChR
      contributes to the regulation of these events. In this report, an aggravating
      role of alpha7 nAChR in host defense against meningitic E. coli infection was
      demonstrated by using alpha7-deficient (alpha7(-/-)) mouse brain microvascular
      endothelial cells (BMEC) and animal model systems. As shown in our in vitro and
      in vivo studies, E. coli K1 invasion and polymorphonuclear neutrophil (PMN)
      transmigration across the blood-brain barrier (BBB) were significantly reduced in
      alpha7(-/-) BMEC and alpha7(-/-) mice. Stimulation by nicotine was abolished in
      the alpha7(-/-) cells and animals. The same blocking effect was achieved by
      methyllycaconitine (alpha7 antagonist). The tight junction molecules occludin and
      ZO-1 were significantly reduced in the brain cortex of wildtype mice infected
      with E. coli and treated with nicotine, compared to alpha7(-/-) cells and
      animals. Decreased neuronal injury in the hippocampal dentate gyrus was observed
      in alpha7(-/-) mice with meningitis. Proinflammatory cytokines (IL-1beta, IL-6,
      TNFalpha, MCP-1, MIP-1alpha, and RANTES) and adhesion molecules (CD44 and ICAM-1)
      were significantly reduced in the cerebrospinal fluids of the alpha7(-/-) mice
      with E. coli meningitis. Furthermore, alpha7 nAChR is the major calcium channel
      for nicotine- and E. coli K1-increased intracellular calcium concentrations of
      mouse BMEC. Taken together, our data suggest that alpha7 nAChR plays a
      detrimental role in the host defense against meningitic infection by modulation
      of pathogen invasion, PMN recruitment, calcium signaling and neuronal
      inflammation.

PMID- 21966400
TI  - Fibrillization of human tau is accelerated by exposure to lead via interaction
      with His-330 and His-362.
AB  - BACKGROUND: Neurofibrillary tangles, mainly consisted of bundles of filaments
      formed by the microtubule-associated protein Tau, are a hallmark of Alzheimer
      disease. Lead is a potent neurotoxin for human being especially for the
      developing children, and Pb(2+) at high concentrations is found in the brains of
      patients with Alzheimer disease. However, it has not been reported so far whether
      Pb(2+) plays a role in the pathology of Alzheimer disease through interaction
      with human Tau protein and thereby mediates Tau filament formation. In this
      study, we have investigated the effect of Pb(2+) on fibril formation of
      recombinant human Tau fragment Tau(244-372) and its mutants at physiological pH.
      METHODOLOGY/PRINCIPAL FINDINGS: As revealed by thioflavin T and 8-anilino-1
      naphthalene sulfonic acid fluorescence, the addition of 5-40 uM Pb(2+)
      significantly accelerates the exposure of hydrophobic region and filament
      formation of wild-type Tau(244-372) on the investigated time scale. As evidenced
      by circular dichroism and Fourier transform infrared spectroscopy, fibrils formed
      by wild-type Tau(244-372) in the presence of 5-40 uM Pb(2+) contain more beta
      sheet structure than the same amount of fibrils formed by the protein in the
      absence of Pb(2+). However, unlike wild-type Tau(244-372), the presence of 5-40
      uM Pb(2+) has no obvious effects on fibrillization kinetics of single mutants
      H330A and H362A and double mutant H330A/H362A, and fibrils formed by such mutants
      in the absence and in the presence of Pb(2+) contain similar amounts of beta
      sheet structure. The results from isothermal titration calorimetry show that one
      Pb(2+) binds to one Tau monomer via interaction with His-330 and His-362, with
      sub-micromolar affinity. CONCLUSIONS/SIGNIFICANCE: We demonstrate for the first
      time that the fibrillization of human Tau protein is accelerated by exposure to
      lead via interaction with His-330 and His-362. Our results suggest the possible
      involvement of Pb(2+) in the pathogenesis of Alzheimer disease and provide
      critical insights into the mechanism of lead toxicity.

PMID- 21966402
TI  - Population growth rates of reef sharks with and without fishing on the great
      barrier reef: robust estimation with multiple models.
AB  - Overfishing of sharks is a global concern, with increasing numbers of species
      threatened by overfishing. For many sharks, both catch rates and underwater
      visual surveys have been criticized as indices of abundance. In this context,
      estimation of population trends using individual demographic rates provides an
      important alternative means of assessing population status. However, such
      estimates involve uncertainties that must be appropriately characterized to
      credibly and effectively inform conservation efforts and management.
      Incorporating uncertainties into population assessment is especially important
      when key demographic rates are obtained via indirect methods, as is often the
      case for mortality rates of marine organisms subject to fishing. Here, focusing
      on two reef shark species on the Great Barrier Reef, Australia, we estimated
      natural and total mortality rates using several indirect methods, and determined
      the population growth rates resulting from each. We used bootstrapping to
      quantify the uncertainty associated with each estimate, and to evaluate the
      extent of agreement between estimates. Multiple models produced highly concordant
      natural and total mortality rates, and associated population growth rates, once
      the uncertainties associated with the individual estimates were taken into
      account. Consensus estimates of natural and total population growth across
      multiple models support the hypothesis that these species are declining rapidly
      due to fishing, in contrast to conclusions previously drawn from catch rate
      trends. Moreover, quantitative projections of abundance differences on fished
      versus unfished reefs, based on the population growth rate estimates, are
      comparable to those found in previous studies using underwater visual surveys.
      These findings appear to justify management actions to substantially reduce the
      fishing mortality of reef sharks. They also highlight the potential utility of
      rigorously characterizing uncertainty, and applying multiple assessment methods,
      to obtain robust estimates of population trends in species threatened by
      overfishing.

PMID- 21966401
TI  - Determining signalling nodes for apoptosis by a genetic high-throughput screen.
AB  - BACKGROUND: With the ever-increasing information emerging from the various
      sequencing and gene annotation projects, there is an urgent need to elucidate the
      cellular functions of the newly discovered genes. The genetically regulated cell
      suicide of apoptosis is especially suitable for such endeavours as it is governed
      by a vast number of factors. METHODOLOGY/PRINCIPAL FINDINGS: We have set up a
      high-throughput screen in 96-well microtiter plates for genes that induce
      apoptosis upon their individual transfection into human cells. Upon screening
      approximately 100,000 cDNA clones we determined 74 genes that initiate this
      cellular suicide programme. A thorough bioinformatics analysis of these genes
      revealed that 91% are novel apoptosis regulators. Careful sequence analysis and
      functional annotation showed that the apoptosis factors exhibit a distinct
      functional distribution that distinguishes the cell death process from other
      signalling pathways. While only a minority of classic signal transducers were
      determined, a substantial number of the genes fall into the transporter- and
      enzyme-category. The apoptosis factors are distributed throughout all cellular
      organelles and many signalling circuits, but one distinct signalling pathway
      connects at least some of the isolated genes. Comparisons with microarray data
      suggest that several genes are dysregulated in specific types of cancers and
      degenerative diseases. CONCLUSIONS/SIGNIFICANCE: Many unknown genes for cell
      death were revealed through our screen, supporting the enormous complexity of
      cell death regulation. Our results will serve as a repository for other
      researchers working with genomics data related to apoptosis or for those seeking
      to reveal novel signalling pathways for cell suicide.

PMID- 21966403
TI  - Quantitative characterization of the influence of the nanoscale morphology of
      nanostructured surfaces on bacterial adhesion and biofilm formation.
AB  - Bacterial infection of implants and prosthetic devices is one of the most common
      causes of implant failure. The nanostructured surface of biocompatible materials
      strongly influences the adhesion and proliferation of mammalian cells on solid
      substrates. The observation of this phenomenon has led to an increased effort to
      develop new strategies to prevent bacterial adhesion and biofilm formation,
      primarily through nanoengineering the topology of the materials used in
      implantable devices. While several studies have demonstrated the influence of
      nanoscale surface morphology on prokaryotic cell attachment, none have provided a
      quantitative understanding of this phenomenon. Using supersonic cluster beam
      deposition, we produced nanostructured titania thin films with controlled and
      reproducible nanoscale morphology respectively. We characterized the surface
      morphology; composition and wettability by means of atomic force microscopy, X
      ray photoemission spectroscopy and contact angle measurements. We studied how
      protein adsorption is influenced by the physico-chemical surface parameters.
      Lastly, we characterized Escherichia coli and Staphylococcus aureus adhesion on
      nanostructured titania surfaces. Our results show that the increase in surface
      pore aspect ratio and volume, related to the increase of surface roughness,
      improves protein adsorption, which in turn downplays bacterial adhesion and
      biofilm formation. As roughness increases up to about 20 nm, bacterial adhesion
      and biofilm formation are enhanced; the further increase of roughness causes a
      significant decrease of bacterial adhesion and inhibits biofilm formation. We
      interpret the observed trend in bacterial adhesion as the combined effect of
      passivation and flattening effects induced by morphology-dependent protein
      adsorption. Our findings demonstrate that bacterial adhesion and biofilm
      formation on nanostructured titanium oxide surfaces are significantly influenced
      by nanoscale morphological features. The quantitative information, provided by
      this study about the relation between surface nanoscale morphology and bacterial
      adhesion points towards the rational design of implant surfaces that control or
      inhibit bacterial adhesion and biofilm formation.

PMID- 21966404
TI  - Hypertriglyceridemia and waist circumference predict cardiovascular risk among
      HIV patients: a cross-sectional study.
AB  - BACKGROUND: Although half of HIV-infected patients develop lipodystrophy and
      metabolic complications, there exists no simple clinical screening tool to
      discern the high from the low-risk HIV-infected patient. Thus, we evaluated the
      associations between waist circumference (WC) combined with triglyceride (TG)
      levels and the severity of lipodystrophy and cardiovascular risk among HIV
      infected men and women. METHODS: 1481 HIV-infected men and 841 HIV-infected women
      were recruited between 2005 and 2009 at the metabolic clinic of the University of
      Modena and Reggio Emilia in Italy. Within each gender, patients were categorized
      into 4 groups according to WC and TG levels. Total and regional fat and fat-free
      mass were assessed by duel-energy x-ray absorptiometry, and visceral adipose
      tissue (VAT) and abdominal subcutaneous AT (SAT) were quantified by computed
      tomography. Various cardiovascular risk factors were assessed in clinic after an
      overnight fast. RESULTS: The high TG/high WC men had the most VAT (208.0 +/- 94.4
      cm(2)), as well as the highest prevalence of metabolic syndrome (42.2%) and type
      2 diabetes (16.2%), and the highest Framingham risk score (10.3 +/- 6.5) in
      comparison to other groups (p<0.05 for all). High TG/high WC women also had
      elevated VAT (150.0 +/- 97.9 cm(2)) and a higher prevalence of metabolic syndrome
      (53.3%), hypertension (30.5%) and type-2 diabetes (12.0%), and Framingham risk
      score(2.9 +/- 2.8) by comparison to low TG/low WC women (p<0.05 for all).
      CONCLUSIONS: A simple tool combining WC and TG levels can discriminate high- from
      low-risk HIV-infected patients.

PMID- 21966405
TI  - New computer-aided diagnosis of dementia using positron emission tomography:
      brain regional sensitivity-mapping method.
AB  - PURPOSE: We devised a new computer-aided diagnosis method to segregate dementia
      using one estimated index (Total Z score) derived from the Brodmann area (BA)
      sensitivity map on the stereotaxic brain atlas. The purpose of this study is to
      investigate its accuracy to differentiate patients with Alzheimer's disease (AD)
      or mild cognitive impairment (MCI) from normal adults (NL). METHODS: We studied
      101 adults (NL: 40, AD: 37, MCI: 24) who underwent (18)FDG positron emission
      tomography (PET) measurement. We divided NL and AD groups into two categories: a
      training group with (Category A) and a test group without (Category B) clinical
      information. In Category A, we estimated sensitivity by comparing the standard
      uptake value per BA (SUVR) between NL and AD groups. Then, we calculated a
      summated index (Total Z score) by utilizing the sensitivity-distribution maps and
      each BA z-score to segregate AD patterns. To confirm the validity of this method,
      we examined the accuracy in Category B. Finally, we applied this method to MCI
      patients. RESULTS: In Category A, we found that the sensitivity and specificity
      of differentiation between NL and AD were all 100%. In Category B, those were
      100% and 95%, respectively. Furthermore, we found this method attained 88% to
      differentiate AD-converters from non-converters in MCI group. CONCLUSIONS: The
      present automated computer-aided evaluation method based on a single estimated
      index provided good accuracy for differential diagnosis of AD and MCI. This good
      differentiation power suggests its usefulness not only for dementia diagnosis but
      also in a longitudinal study.

PMID- 21966406
TI  - Genetic variation in virulence among chalkbrood strains infecting honeybees.
AB  - Ascosphaera apis causes chalkbrood in honeybees, a chronic disease that reduces
      the number of viable offspring in the nest. Although lethal for larvae, the
      disease normally has relatively low virulence at the colony level. A recent study
      showed that there is genetic variation for host susceptibility, but whether
      Ascosphaera apis strains differ in virulence is unknown. We exploited a recently
      modified in vitro rearing technique to infect honeybee larvae from three colonies
      with naturally mated queens under strictly controlled laboratory conditions,
      using four strains from two distinct A. apis clades. We found that both strain
      and colony of larval origin affected mortality rates. The strains from one clade
      caused 12-14% mortality while those from the other clade induced 71-92%
      mortality. Larvae from one colony showed significantly higher susceptibility to
      chalkbrood infection than larvae from the other two colonies, confirming the
      existence of genetic variation in susceptibility across colonies. Our results are
      consistent with antagonistic coevolution between a specialized fungal pathogen
      and its host, and suggest that beekeeping industries would benefit from more
      systematic monitoring of this chronic stress factor of their colonies.

PMID- 21966407
TI  - The agent is right: when motor embodied cognition is space-dependent.
AB  - The role of embodied mechanisms in processing sentences endowed with a first
      person perspective is now widely accepted. However, whether embodied sentence
      processing within a third person perspective would also have motor behavioral
      significance remains unknown. Here, we developed a novel version of the Action
      sentence Compatibility Effect (ACE) in which participants were asked to perform a
      movement compatible or not with the direction embedded in a sentence having a
      first person (Experiment 1: You gave a pizza to Louis) or third person
      perspective (Experiment 2: Lea gave a pizza to Louis). Results indicate that
      shifting perspective from first to third person was sufficient to prevent motor
      embodied mechanisms, abolishing the ACE. Critically, ACE was restored in
      Experiment 3 by adding a virtual "body" that allowed participants to know "where"
      to put themselves in space when taking the third person perspective, thus
      demonstrating that motor embodied processes are space-dependent. A fourth,
      control experiment, by dissociating motor response from the transfer verb's
      direction, supported the conclusion that perspective-taking may induce
      significant ACE only when coupled with the adequate sentence-response mapping.

PMID- 21966408
TI  - Pyrosequencing-based analysis of the mucosal microbiota in healthy individuals
      reveals ubiquitous bacterial groups and micro-heterogeneity.
AB  - This study used 16S rRNA-based pyrosequencing to examine the microbial community
      that is closely associated with the colonic mucosa of five healthy individuals.
      Spatial heterogeneity in microbiota was measured at right colon, left colon and
      rectum, and between biopsy duplicates spaced 1 cm apart. The data demonstrate
      that mucosal-associated microbiota is comprised of Firmicutes (50.9% +/- 21.3%),
      Bacteroidetes (40.2% +/- 23.8%) and Proteobacteria (8.6%+/- 4.7%), and that
      interindividual differences were apparent. Among the genera, Bacteroides,
      Leuconostoc and Weissella were present at high abundance (4.6% to 41.2%) in more
      than 90% of the studied biopsy samples. Lactococcus, Streptococcus, Acidovorax,
      Acinetobacter, Blautia, Faecalibacterium, Veillonella, and several unclassified
      bacterial groups were also ubiquitously present at an abundance <7.0% of total
      microbial community. With the exception of one individual, the mucosal-associated
      microbiota was relatively homogeneous along the colon (average 61% Bray-Curtis
      similarity). However, micro-heterogeneity was observed in biopsy duplicates
      within defined colonic sites for three of the individuals. A weak but significant
      Mantel correlation of 0.13 was observed between the abundance of acidomucins and
      mucosal-associated microbiota (P-value = 0.04), indicating that the localized
      biochemical differences may contribute in part to the micro-heterogeneity. This
      study provided a detailed insight to the baseline mucosal microbiota along the
      colon, and revealed the existence of micro-heterogeneity within defined colonic
      sites for certain individuals.

PMID- 21966410
TI  - Derivation of rhesus monkey parthenogenetic embryonic stem cells and its microRNA
      signature.
AB  - Parthenogenetic embryonic stem cells are considered as a promising resource for
      regeneration medicine and powerful tools for developmental biology. A lot of
      studies have revealed that embryonic stem cells have distinct microRNA expression
      pattern and these microRNAs play important roles in self-renewal and pluripotency
      of embryonic stem cells. However, few studies concern about microRNA expression
      pattern in parthenogenetic embryonic stem cells, especially in non-human primate-
      the ideal model species for human, largely due to the limited rhesus monkey
      parthenogenetic embryonic stem cells (rpESCs) available and lack of systematic
      analysis of the basics of rpESCs. Here, we derived two novel rpESCs lines and
      characterized their microRNA signature by Solexa deep sequencing. These two novel
      rpESCs shared many properties with other primate ESCs, including expression of
      pluripotent markers, capacity to generate derivatives representative of all three
      germ layers in vivo and in vitro, maintaining of euploid karyotype even after
      long culture. Additionally, lack of some paternally expressed imprinted genes and
      identity of Single-nucleotide Polymorphism (SNP) compare to their oocyte donors
      support their parthenogenesis origin. By characterizing their microRNA signature,
      we identified 91 novel microRNAs, except those are also detected in other primate
      ESCs. Moreover, these two novel rpESCs display a unique microRNA signature,
      comparing to their biparental counterpart ESCs. Then we analyzed X chromosome
      status in these two novel rpESCs; results suggested that one of them possesses
      two active X chromosomes, the other possesses only one active X chromosome liking
      biparental female embryonic stem cells. Taken together, our novel rpESCs provide
      a new alternative to existing rhesus monkey embryonic stem cells, microRNA
      information expands rhesus monkey microRNA data and may help understanding
      microRNA roles in pluripotency and parthenogenesis.

PMID- 21966409
TI  - Protein 4.1B contributes to the organization of peripheral myelinated axons.
AB  - Neurons are characterized by extremely long axons. This exceptional cell shape is
      likely to depend on multiple factors including interactions between the
      cytoskeleton and membrane proteins. In many cell types, members of the protein
      4.1 family play an important role in tethering the cortical actin-spectrin
      cytoskeleton to the plasma membrane. Protein 4.1B is localized in myelinated
      axons, enriched in paranodal and juxtaparanodal regions, and also all along the
      internodes, but not at nodes of Ranvier where are localized the voltage-dependent
      sodium channels responsible for action potential propagation. To shed light on
      the role of protein 4.1B in the general organization of myelinated peripheral
      axons, we studied 4.1B knockout mice. These mice displayed a mildly impaired gait
      and motility. Whereas nodes were unaffected, the distribution of Caspr/paranodin,
      which anchors 4.1B to the membrane, was disorganized in paranodal regions and its
      levels were decreased. In juxtaparanodes, the enrichment of Caspr2, which also
      interacts with 4.1B, and of the associated TAG-1 and Kv1.1, was absent in mutant
      mice, whereas their levels were unaltered. Ultrastructural abnormalities were
      observed both at paranodes and juxtaparanodes. Axon calibers were slightly
      diminished in phrenic nerves and preterminal motor axons were dysmorphic in
      skeletal muscle. betaII spectrin enrichment was decreased along the axolemma.
      Electrophysiological recordings at 3 post-natal weeks showed the occurrence of
      spontaneous and evoked repetitive activity indicating neuronal hyperexcitability,
      without change in conduction velocity. Thus, our results show that in myelinated
      axons 4.1B contributes to the stabilization of membrane proteins at paranodes, to
      the clustering of juxtaparanodal proteins, and to the regulation of the
      internodal axon caliber.

PMID- 21966411
TI  - Thyroid hormone promotes remodeling of coronary resistance vessels.
AB  - Low thyroid hormone (TH) function has been linked to impaired coronary blood
      flow, reduced density of small arterioles, and heart failure. Nonetheless, little
      is known about the mechanisms by which THs regulate coronary microvascular
      remodeling. The current study examined the initial cellular events associated
      with coronary remodeling induced by triiodothyronine (T3) in hypothyroid rats.
      Rats with established hypothyroidism, eight weeks after surgical thyroidectomy
      (TX), were treated with T3 for 36 or 72 hours. The early effects of T3 treatment
      on coronary microvasculature were examined morphometrically. Gene expression
      changes in the heart were assessed by quantitative PCR Array. Hypothyroidism
      resulted in arteriolar atrophy in the left ventricle. T3 treatment rapidly
      induced small arteriolar muscularization and, within 72 hours, restored
      arteriolar density to control levels. Total length of the capillary network was
      not affected by TX or T3 treatment. T3 treatment resulted in the coordinate
      regulation of Angiopoietin 1 and 2 expression. The response of Angiopoietins was
      consistent with vessel enlargement. In addition to the well known effects of THs
      on vasoreactivity, these results suggest that THs may affect function of small
      resistance arteries by phenotypic remodeling of vascular smooth muscle cells
      (VSMC).

PMID- 21966412
TI  - Predicting peptide binding affinities to MHC molecules using a modified semi
      empirical scoring function.
AB  - The Major Histocompatibility Complex (MHC) plays an important role in the human
      immune system. The MHC is involved in the antigen presentation system assisting T
      cells to identify foreign or pathogenic proteins. However, an MHC molecule
      binding a self-peptide may incorrectly trigger an immune response and cause an
      autoimmune disease, such as multiple sclerosis. Understanding the molecular
      mechanism of this process will greatly assist in determining the aetiology of
      various diseases and in the design of effective drugs. In the present study, we
      have used the Fresno semi-empirical scoring function and modify the approach to
      the prediction of peptide-MHC binding by using open-source and public domain
      software. We apply the method to HLA class II alleles DR15, DR1, and DR4, and the
      HLA class I allele HLA A2. Our analysis shows that using a large set of binding
      data and multiple crystal structures improves the predictive capability of the
      method. The performance of the method is also shown to be correlated to the
      structural similarity of the crystal structures used. We have exposed some of the
      obstacles faced by structure-based prediction methods and proposed possible
      solutions to those obstacles. It is envisaged that these obstacles need to be
      addressed before the performance of structure-based methods can be on par with
      the sequence-based methods.

PMID- 21966413
TI  - Smoking related cancers and loci at chromosomes 15q25, 5p15, 6p22.1 and 6p21.33
      in the Polish population.
AB  - Genetic factors associated with the risk of smoking related cancers have until
      recently remained elusive. Since the publication of a genome-wide association
      study (GWAS) on lung cancer new genetic loci have been identified that appear to
      be associated with disease risk. In this replication study we genotyped 14 single
      nucleotide polymorphisms (SNPs) located at the 5p12.3-p15.33, 6p21.3-p22.1, 6q23
      q27 and 15q25.1 loci in 874 lung, 450 bladder, 418 laryngeal cancer cases and
      cancer-free controls, matched by year of birth and sex to the cases. Our results
      revealed that loci in the chromosome region 15q25.1 (rs16969968[A], rs8034191[G])
      and 5p15 (rs402710[T]) are associated with lung cancer risk in the Polish
      population (smoking status adjusted OR = 1.45, 1.35, 0.77; p <= 0.0001, 0.0005,
      0.002; 95%CI 1.23-1.72, 1.14-1.59, 0.66-0.91 respectively). None of the other
      regions analyzed herein were implicated in the risk of lung, bladder or laryngeal
      cancer. This study supports previous findings on lung cancer but fails to show
      association of SNPs located in 15q25.1 and 5p15 region with other smoking related
      cancers like bladder and laryngeal cancer.

PMID- 21966414
TI  - Changes in cytokine levels and NK cell activation associated with influenza.
AB  - Several studies have highlighted the important role played by murine natural
      killer (NK) cells in the control of influenza infection. However, human NK cell
      responses in acute influenza infection, including infection with the 2009
      pandemic H1N1 influenza virus, are poorly documented. Here, we examined changes
      in NK cell phenotype and function and plasma cytokine levels associated with
      influenza infection and vaccination. We show that absolute numbers of peripheral
      blood NK cells, and particularly those of CD56(bright) NK cells, decreased upon
      acute influenza infection while this NK cell subset expanded following
      intramuscular influenza vaccination. NK cells exposed to influenza antigens were
      activated, with higher proportions of NK cells expressing CD69 in study subjects
      infected with seasonal influenza strains. Vaccination led to increased levels of
      CD25+ NK cells, and notably CD56(bright) CD25+ NK cells, whereas decreased
      amounts of this subset were present in the peripheral blood of influenza infected
      individuals, and predominantly in study subjects infected with the 2009 pandemic
      H1N1 influenza virus. Finally, acute influenza infection was associated with low
      plasma concentrations of inflammatory cytokines, including IFN-gamma, MIP-1beta,
      IL-2 and IL-15, and high levels of the anti-inflammatory cytokines IL-10 and IL
      1ra. Altogether, these data suggest a role for the CD56(bright) NK cell subset in
      the response to influenza, potentially involving their recruitment to infected
      tissues and a local production and/or uptake of inflammatory cytokines.

PMID- 21966415
TI  - CD4+FoxP3+ regulatory T cells from Galphai2-/- mice are functionally active in
      vitro, but do not prevent colitis.
AB  - BACKGROUND: Mice deficient in the inhibitory G protein subunit Galphai2
      spontaneously develop a T helper 1 dominated colitis. We examined whether a
      defect in CD4(+)FoxP3(+) regulatory T cells (Treg) underpins the pathogenesis of
      colitis in the Galphai2(-/-) (Galphai2-deficient) colitis model.
      METHODOLOGY/PRINCIPAL FINDINGS: Using flow cytometry, we found that thymus and
      colonic lamina propria, but not spleen and mesenteric lymph nodes, of colitic
      Galphai2(-/-) mice contained increased frequencies of Treg, whereas FoxP3
      expression intensity was similar in Galphai2(-/-) compared to Galphai2(+/-) or
      Galphai2(+/+) wild type (WT) mice. The frequency of CD4(+)FoxP3(+) T cells
      expressing CD103 was significantly increased in Galphai2(-/-) compared to WT
      mice. Treg in colons from WT mice clustered in the T cell areas of colonic
      lymphoid patches (CLP), with relatively few Treg in the lamina propria, as
      demonstrated by immunohistochemistry. In Galphai2(-/-) mice, CLP were not
      observed but lamina propria Treg were increased in number and frequency within
      the CD4(+) infiltrate, compared to WT mice. Using an in vitro co-culture system
      and flow cytometric analysis of cell division we could demonstrate that the in
      vitro suppressive function of WT and Galphai2(-/-) CD4(+)FoxP3(+) regulatory T
      cells (WT-Treg and KO-Treg) was indistinguishable, but that T effector cells
      (CD4(+)25(-) T cells) from Galphai2(-/-) mice were less readily suppressed than
      WT effectors (WT-Teff) by Treg from either source. However, neither WT nor
      Galphai2(-/-) Treg was able to suppress colitis induced by adoptive transfer of
      Galphai2(-/-) effector T cells (KO-Teff) to RAG2(-/-) recipients. The enhanced
      inflammatory activity of Galphai2(-/-) effectors was accompanied by increased
      expression of an effector/memory T cell phenotype and increased cytokine
      secretion, especially IL-4, IL-6 and IFN-gamma. CONCLUSIONS: There is an
      increased frequency of Galphai2(-/-) Treg in the colon, and they demonstrate no
      endogenous functional defect. However, Galphai2(-/-) T effector cells are
      dramatically less susceptible to suppression in vitro, and in vivo, despite
      increased effective numbers of Treg, they cannot prevent disease.

PMID- 21966417
TI  - Differential impact of EGFR-targeted therapies on hypoxia responses: implications
      for treatment sensitivity in triple-negative metastatic breast cancer.
AB  - BACKGROUND: In solid tumors, such as breast cancer, cells are exposed to hypoxia.
      Cancer cells adapt their metabolism by activating hypoxia-inducible factors
      (HIFs) that promote the transcription of genes involved in processes such as cell
      survival, drug resistance and metastasis. HIF-1 is also induced in an oxygen
      independent manner through the activation of epidermal growth factor receptor
      tyrosine kinase (EGFR-TK). Triple-negative breast cancer (TNBC) is a subtype of
      invasive breast cancer characterized by negative expression of hormonal and HER2
      receptors, and this subtype generally overexpresses EGFR. Sensitivity to three
      EGFR inhibitors (cetuximab, gefitinib and lapatinib, an HER2/EGFR-TK inhibitor)
      was evaluated in a metastatic TNBC cell model (MDA-MB-231), and the impact of
      these drugs on the activity and stability of HIF was assessed.
      METHODOLOGY/PRINCIPAL FINDINGS: MDA-MB-231 cells were genetically modified to
      stably express an enhanced green fluorescent protein (EGFP) induced by hypoxia;
      the Ca9-GFP cell model reports HIF activity, whereas GFP-P564 reports HIF
      stability. The reporter signal was monitored by flow cytometry. HIF-1 DNA-binding
      activity, cell migration and viability were also evaluated in response to EGFR
      inhibitors. Cell fluorescence signals strongly increased under hypoxic conditions
      (> 30-fold). Cetuximab and lapatinib did not affect the signal induced by
      hypoxia, whereas gefitinib sharply reduced its intensity in both cell models and
      also diminished HIF-1 alpha levels and HIF-1 DNA-binding activity in MDA-MB-231
      cells. This gefitinib feature was associated with its ability to inhibit MDA-MB
      231 cell migration and to induce cell mortality in a dose-dependent manner.
      Cetuximab and lapatinib had no effect on cell migration or cell viability.
      CONCLUSION: Resistance to cetuximab and lapatinib and sensitivity to gefitinib
      were associated with their ability to modulate HIF activity and stability. In
      conclusion, downregulation of HIF-1 through EGFR signaling seems to be required
      for the induction of a positive response to EGFR-targeted therapies in TNBC.

PMID- 21966416
TI  - Mycobacterium tuberculosis lipolytic enzymes as potential biomarkers for the
      diagnosis of active tuberculosis.
AB  - BACKGROUND: New diagnosis tests are urgently needed to address the global
      tuberculosis (TB) burden and to improve control programs especially in resource
      limited settings. An effective in vitro diagnostic of TB based on serological
      methods would be regarded as an attractive progress because immunoassays are
      simple, rapid, inexpensive, and may offer the possibility to detect cases missed
      by standard sputum smear microscopy. However, currently available serology tests
      for TB are highly variable in sensitivity and specificity. Lipolytic enzymes have
      recently emerged as key factors in lipid metabolization during dormancy and/or
      exit of the non-replicating growth phase, a prerequisite step of TB reactivation.
      The focus of this study was to analyze and compare the potential of four
      Mycobacterium tuberculosis lipolytic enzymes (LipY, Rv0183, Rv1984c and Rv3452)
      as new markers in the serodiagnosis of active TB. METHODS: Recombinant proteins
      were produced and used in optimized ELISA aimed to detect IgG and IgM serum
      antibodies against the four lipolytic enzymes. The capacity of the assays to
      identify infection was evaluated in patients with either active TB or latent TB
      and compared with two distinct control groups consisting of BCG-vaccinated blood
      donors and hospitalized non-TB individuals. RESULTS: A robust humoral response
      was detected in patients with active TB whereas antibodies against lipolytic
      enzymes were infrequently detected in either uninfected groups or in subjects
      with latent infection. High specifity levels, ranging from 93.9% to 97.5%, were
      obtained for all four antigens with sensitivity values ranging from 73.4% to
      90.5%, with Rv3452 displaying the highest performances. Patients with active TB
      usually exhibited strong IgG responses but poor IgM responses. CONCLUSION: These
      results clearly indicate that the lipolytic enzymes tested are strongly
      immunogenic allowing to distinguish active from latent TB infections. They appear
      as potent biomarkers providing high sensitivity and specificity levels for the
      immunodiagnosis of active TB.

PMID- 21966418
TI  - Comparing COI and ITS as DNA barcode markers for mushrooms and allies
      (Agaricomycotina).
AB  - DNA barcoding is an approach to rapidly identify species using short, standard
      genetic markers. The mitochondrial cytochrome oxidase I gene (COI) has been
      proposed as the universal barcode locus, but its utility for barcoding in
      mushrooms (ca. 20,000 species) has not been established. We succeeded in
      generating 167 partial COI sequences (~450 bp) representing ~100 morphospecies
      from ~650 collections of Agaricomycotina using several sets of new primers. Large
      introns (~1500 bp) at variable locations were detected in ~5% of the sequences we
      obtained. We suspect that widespread presence of large introns is responsible for
      our low PCR success (~30%) with this locus. We also sequenced the nuclear
      internal transcribed spacer rDNA regions (ITS) to compare with COI. Among the
      small proportion of taxa for which COI could be sequenced, COI and ITS perform
      similarly as a barcode. However, in a densely sampled set of closely related
      taxa, COI was less divergent than ITS and failed to distinguish all terminal
      clades. Given our results and the wealth of ITS data already available in public
      databases, we recommend that COI be abandoned in favor of ITS as the primary DNA
      barcode locus in mushrooms.

PMID- 21966420
TI  - Judgment of the humanness of an interlocutor is in the eye of the beholder.
AB  - Despite tremendous advances in artificial language synthesis, no machine has so
      far succeeded in deceiving a human. Most research focused on analyzing the
      behavior of "good" machine. We here choose an opposite strategy, by analyzing the
      behavior of "bad" humans, i.e., humans perceived as machine. The Loebner Prize in
      Artificial Intelligence features humans and artificial agents trying to convince
      judges on their humanness via computer-mediated communication. Using this setting
      as a model, we investigated here whether the linguistic behavior of human
      subjects perceived as non-human would enable us to identify some of the core
      parameters involved in the judgment of an agents' humanness. We analyzed
      descriptive and semantic aspects of dialogues in which subjects succeeded or
      failed to convince judges of their humanness. Using cognitive and emotional
      dimensions in a global behavioral characterization, we demonstrate important
      differences in the patterns of behavioral expressiveness of the judges whether
      they perceived their interlocutor as being human or machine. Furthermore, the
      indicators of interest displayed by the judges were predictive of the final
      judgment of humanness. Thus, we show that the judgment of an interlocutor's
      humanness during a social interaction depends not only on his behavior, but also
      on the judge himself. Our results thus demonstrate that the judgment of humanness
      is in the eye of the beholder.

PMID- 21966419
TI  - Biochemical, structural and molecular dynamics analyses of the potential
      virulence factor RipA from Yersinia pestis.
AB  - Human diseases are attributed in part to the ability of pathogens to evade the
      eukaryotic immune systems. A subset of these pathogens has developed mechanisms
      to survive in human macrophages. Yersinia pestis, the causative agent of the
      bubonic plague, is a predominately extracellular pathogen with the ability to
      survive and replicate intracellularly. A previous study has shown that a novel
      rip (required for intracellular proliferation) operon (ripA, ripB and ripC) is
      essential for replication and survival of Y. pestis in postactivated macrophages,
      by playing a role in lowering macrophage-produced nitric oxide (NO) levels. A
      bioinformatics analysis indicates that the rip operon is conserved among a
      distally related subset of macrophage-residing pathogens, including Burkholderia
      and Salmonella species, and suggests that this previously uncharacterized pathway
      is also required for intracellular survival of these pathogens. The focus of this
      study is ripA, which encodes for a protein highly homologous to 4-hydroxybutyrate
      CoA transferase; however, biochemical analysis suggests that RipA functions as a
      butyryl-CoA transferase. The 1.9 A X-ray crystal structure reveals that RipA
      belongs to the class of Family I CoA transferases and exhibits a unique
      tetrameric state. Molecular dynamics simulations are consistent with RipA
      tetramer formation and suggest a possible gating mechanism for CoA binding
      mediated by Val227. Together, our structural characterization and molecular
      dynamic simulations offer insights into acyl-CoA specificity within the active
      site binding pocket, and support biochemical results that RipA is a butyryl-CoA
      transferase. We hypothesize that the end product of the rip operon is butyrate, a
      known anti-inflammatory, which has been shown to lower NO levels in macrophages.
      Thus, the results of this molecular study of Y. pestis RipA provide a structural
      platform for rational inhibitor design, which may lead to a greater understanding
      of the role of RipA in this unique virulence pathway.

PMID- 21966421
TI  - Effect of D222G mutation in the hemagglutinin protein on receptor binding,
      pathogenesis and transmissibility of the 2009 pandemic H1N1 influenza virus.
AB  - Influenza viruses isolated during the 2009 H1N1 pandemic generally lack known
      molecular determinants of virulence associated with previous pandemic and highly
      pathogenic avian influenza viruses. The frequency of the amino acid substitution
      D222G in the hemagglutinin (HA) of 2009 H1N1 viruses isolated from severe but not
      mild human cases represents the first molecular marker associated with enhanced
      disease. To assess the relative contribution of this substitution in virus
      pathogenesis, transmission, and tropism, we introduced D222G by reverse genetics
      in the wild-type HA of the 2009 H1N1 virus, A/California/04/09 (CA/04). A dose
      dependent glycan array analysis with the D222G virus showed a modest reduction in
      the binding avidity to human-like (alpha2-6 sialylated glycan) receptors and an
      increase in the binding to avian-like (alpha2-3 sialylated glycan) receptors in
      comparison with wild-type virus. In the ferret pathogenesis model, the D222G
      mutant virus was found to be similar to wild-type CA/04 virus with respect to
      lethargy, weight loss and replication efficiency in the upper and lower
      respiratory tract. Moreover, based on viral detection, the respiratory droplet
      transmission properties of these two viruses were found to be similar. The D222G
      virus failed to productively infect mice inoculated by the ocular route, but
      exhibited greater viral replication and weight loss than wild-type CA/04 virus in
      mice inoculated by the intranasal route. In a more relevant human cell model,
      D222G virus replicated with delayed kinetics compared with wild-type virus but to
      higher titer in human bronchial epithelial cells. These findings suggest that
      although the D222G mutation does not influence virus transmission, it may be
      considered a molecular marker for enhanced replication in certain cell types.

PMID- 21966422
TI  - Protection of melanized Cryptococcus neoformans from lethal dose gamma
      irradiation involves changes in melanin's chemical structure and paramagnetism.
AB  - Certain fungi thrive in highly radioactive environments including the defunct
      Chernobyl nuclear reactor. Cryptococcus neoformans (C. neoformans), which uses L
      3,4-dihydroxyphenylalanine (L-DOPA) to produce melanin, was used here to
      investigate how gamma radiation under aqueous aerobic conditions affects the
      properties of melanin, with the aim of gaining insight into its radioprotective
      role. Exposure of melanized fungal cell in aqueous suspensions to doses of gamma
      radiation capable of killing 50 to 80% of the cells did not lead to a detectable
      loss of melanin integrity according to EPR spectra of melanin radicals. Moreover,
      upon UV-visible (Xe-lamp) illumination of melanized cells, the increase in
      radical population was unchanged after gamma-irradiation. Gamma-irradiation of
      frozen cell suspensions and storage of samples for several days at 77 K however,
      produced melanin modification noted by a reduced radical population and reduced
      photoresponse. More direct evidence for structural modification of melanin came
      from the detection of soluble products with absorbance maxima near 260 nm in
      supernatants collected after gamma-irradiation of cells and cell-free melanin.
      These products, which include thiobarbituric acid (TBA)-reactive aldehydes, were
      also generated by Fenton reagent treatment of cells and cell-free melanin. In an
      assay of melanin integrity based on the metal (Bi(+3)) binding capacity of cells,
      no detectable loss in binding was detected after gamma-irradiation. Our results
      show that melanin in C. neoformans cells is susceptible to some damage by
      hydroxyl radical formed in lethal radioactive aqueous environments and serves a
      protective role in melanized fungi that involves sacrificial breakdown.

PMID- 21966423
TI  - Imaging pulmonary NF-kappaB activation and therapeutic effects of MLN120B and
      TDZD-8.
AB  - NF-kappaB activation is a critical signaling event in the inflammatory response
      and has been implicated in a number of pathological lung diseases. To enable the
      assessment of NF-kappaB activity in the lungs, we transfected a luciferase based
      NF-kappaB reporter into the lungs of mice or into Raw264.7 cells in culture. The
      transfected mice showed specific luciferase expression in the pulmonary tissues.
      Using these mouse models, we studied the kinetics of NF-kappaB activation
      following exposure to lipopolysaccharide (LPS). The Raw264.7 cells expressed a
      dose-dependent increase in luciferase following exposure to LPS and the NF-kappaB
      reporter mice expressed luciferase in the lungs following LPS challenge,
      establishing that bioluminescence imaging provides adequate sensitivity for
      tracking the NF-kappaB activation pathway. Interventions affecting the NF-kappaB
      pathway are promising clinical therapeutics, thus we further examined the effect
      of IKK-2 inhibition by MLN120B and glycogen synthase kinase 3 beta inhibition by
      TDZD-8 on NF-kappaB activation. Pre-treatment with either MLN120B or TDZD-8
      attenuated NF-kappaB activation in the pulmonary tissues, which was accompanied
      with suppression of pro-inflammatory chemokine MIP-1beta and induction of anti
      inflammatory cytokine IL-10. In summary, we have established an imaging based
      approach for non-invasive and longitudinal assessment of NF-kappaB activation and
      regulation during acute lung injury. This approach will potentiate further
      studies on NF-kappaB regulation under various inflammatory conditions.

PMID- 21966424
TI  - Genomic profiling identifies novel mutations and SNPs in ABCD1 gene: a molecular,
      biochemical and clinical analysis of X-ALD cases in India.
AB  - X-linked adrenoleukodystrophy (X-ALD) affects the nervous system white matter and
      adrenal cortex secondary to mutations in the ABCD1 gene that encode the
      peroxisomal membrane protein. We conducted a genomic and protein expression study
      of susceptibility gene with its clinical and biochemical analysis. To the best of
      our knowledge this is the first preliminary comprehensive study in Indian
      population that identified novel mutations and SNPs in a relatively large group.
      We screened 17 Indian indigenous X-linked adrenoleukodystrophy cases and 70
      controls for mutations and SNPs in the exonic regions (including flanking
      regions) of ABCD1 gene by direct sequencing with ABI automated sequencer along
      with Western blot analysis of its endogenous protein, ALDP, levels in peripheral
      blood mononuclear cells. Single germ line mutation was identified in each index
      case in ABCD1 gene. We detected 4 novel mutations (2 missense and 2
      deletion/insertion) and 3 novel single nucleotide polymorphisms. We observed a
      variable protein expression in different patients. These findings were further
      extended to biochemical and clinical observations as it occurs with great
      clinical expression variability. This is the first major study in this population
      that presents a different molecular genetic spectrum as compared to Caucasian
      population due to geographical distributions of ethnicity of patients. It
      enhances our knowledge of the causative mutations of X-ALD that grants holistic
      base to develop effective medicine against X-ALD.

PMID- 21966425
TI  - Estimating pneumonia deaths of post-neonatal children in countries of low or no
      death certification in 2008.
AB  - BACKGROUND: Pneumonia is the leading cause of child deaths globally. The aims of
      this study were to: a) estimate the number and global distribution of pneumonia
      deaths for children 1-59 months for 2008 for countries with low (<85%) or no
      coverage of death certification using single-cause regression models and b)
      compare these country estimates with recently published ones based on multi-cause
      regression models. METHODS AND FINDINGS: For 35 low child-mortality countries
      with <85% coverage of death certification, a regression model based on vital
      registration data of low child-mortality and >85% coverage of death certification
      countries was used. For 87 high child-mortality countries pneumonia death
      estimates were obtained by applying a regression model developed from published
      and unpublished verbal autopsy data from high child-mortality settings. The total
      number of 1-59 months pneumonia deaths for the year 2008 for these 122 countries
      was estimated to be 1.18 M (95% CI 0.77 M-1.80 M), which represented 23.27% (95%
      CI 17.15%-32.75%) of all 1-59 month child deaths. The country level estimation
      correlation coefficient between these two methods was 0.40. INTERPRETATION:
      Although the overall number of post-neonatal pneumonia deaths was similar
      irrespective to the method of estimation used, the country estimate correlation
      coefficient was low, and therefore country-specific estimates should be
      interpreted with caution. Pneumonia remains the leading cause of child deaths and
      is greatest in regions of poverty and high child-mortality. Despite the concerns
      about gender inequity linked with childhood mortality we could not estimate sex
      specific pneumonia mortality rates due to the inadequate data. Life-saving
      interventions effective in preventing and treating pneumonia mortality exist but
      few children in high pneumonia disease burden regions are able to access them. To
      achieve the United Nations Millennium Development Goal 4 target to reduce child
      deaths by two-thirds in year 2015 will require the scale-up of access to these
      effective pneumonia interventions.

PMID- 21966426
TI  - Fine-tuning roles of endogenous brain-derived neurotrophic factor, TrkB and
      sortilin in colorectal cancer cell survival.
AB  - BACKGROUND: Neurotrophin receptors were initially identified in neural cells.
      They were recently detected in some cancers in association with invasiveness, but
      the function of these tyrosine kinase receptors was not previously investigated
      in colorectal cancer (CRC) cells. METHODS AND FINDINGS: We report herein that
      human CRC cell lines synthesize the neural growth factor Brain-derived
      neurotrophic factor (BDNF) under stress conditions (serum starvation). In
      parallel, CRC cells expressed high- (TrkB) and low-affinity (p75(NTR)) receptors
      at the plasma membrane, whereas TrkA and TrkC, two other high affinity receptors
      for NGF and NT-3, respectively, were undetectable. We demonstrate that BDNF
      induced cell proliferation and had an anti-apoptotic effect mediated through
      TrkB, as assessed by K252a, a Trk pharmacologic inhibitor. It suppressed both
      cell proliferation and survival of CRC cells that do not express TrkA nor TrkC.
      In parallel to the increase of BDNF secretion, sortilin, a protein acting as a
      neurotrophin transporter as well as a co-receptor for p75(NTR), was increased in
      the cytoplasm of primary and metastatic CRC cells, which suggests that sortilin
      could regulate neurotrophin transport in these cells. However, pro-BDNF, also
      detected in CRC cells, was co-expressed with p75(NTR) at the cell membrane and co
      localized with sortilin. In contrast to BDNF, exogenous pro-BDNF induced CRC
      apoptosis, which suggests that a counterbalance mechanism is involved in the
      control of CRC cell survival, through sortilin as the co-receptor for p75(NTR),
      the high affinity receptor for pro-neurotrophins. Likewise, we show that BDNF and
      TrkB transcripts (and not p75(NTR)) are overexpressed in the patients' tumors by
      comparison with their adjacent normal tissues, notably in advanced stages of CRC.
      CONCLUSION: Taken together, these results highlight that BDNF and TrkB are
      essential for CRC cell growth and survival in vitro and in tumors. This autocrine
      loop could be of major importance to define new targeted therapies.

PMID- 21966427
TI  - Genetic variants of TSLP and asthma in an admixed urban population.
AB  - BACKGROUND: Thymic stromal lymphopoietin (TSLP), an IL7-like cytokine produced by
      bronchial epithelial cells is upregulated in asthma and induces dendritic cell
      maturation supporting a Th2 response. Environmental pollutants, including tobacco
      smoke and diesel exhaust particles upregulate TSLP suggesting that TSLP may be an
      interface between environmental pollution and immune responses in asthma. Since
      asthma is prevalent in urban communities, variants in the TSLP gene may be
      important in asthma susceptibility in these populations. OBJECTIVES: To determine
      whether genetic variants in TSLP are associated with asthma in an urban admixed
      population.  METHODOLOGY AND MAIN RESULTS: Ten tag-SNPs in the TSLP gene were
      analyzed for association with asthma using 387 clinically diagnosed asthmatic
      cases and 212 healthy controls from an urban admixed population. One SNP
      (rs1898671) showed nominally significant association with asthma (odds ratio (OR)
      = 1.50; 95% confidence interval (95% CI): 1.09-2.05, p = 0.01) after adjusting
      for age, BMI, income, education and population stratification. Association
      results were consistent using two different approaches to adjust for population
      stratification. When stratified by smoking status, the same SNP showed a
      significantly increased risk associated with asthma in ex-smokers (OR = 2.00, 95%
      CI: 1.04-3.83, p = 0.04) but not significant in never-smokers (OR = 1.34; 95% CI:
      0.93-1.94, p = 0.11). Haplotype-specific score test indicated that an elevated
      risk for asthma was associated with a specific haplotype of TSLP involving SNP
      rs1898671 (OR = 1.58, 95% CI: 1.10-2.27, p = 0.01). Association of this SNP with
      asthma was confirmed in an independent large population-based cohort consortium
      study (OR = 1.15, 95% CI: 1.07-1.23, p = 0.0003) and the results stratified by
      smoking status were also validated (ex-smokers: OR = 1.21, 95% CI: 1.08-1.34, p =
      0.003; never-smokers: OR = 1.06, 95% CI: 0.94-1.17, p = 0.33). CONCLUSIONS:
      Genetic variants in TSLP may contribute to asthma susceptibility in admixed urban
      populations with a gene and environment interaction.

PMID- 21966428
TI  - Galectin-3 facilitates cell motility in gastric cancer by up-regulating protease
      activated receptor-1 (PAR-1) and matrix metalloproteinase-1 (MMP-1).
AB  - BACKGROUND: Galectin-3 is known to regulate cancer metastasis. However, the
      underlying mechanism has not been defined. Through the DNA microarray studies
      after galectin-3 silencing, we demonstrated here that galectin-3 plays a key role
      in up-regulating the expressions of protease-activated receptor-1 (PAR-1) and
      matrix metalloproteinase-1 (MMP-1) PAR-1 thereby promoting gastric cancer
      metastasis. METHODOLOGY/PRINCIPAL FINDINGS: We examined the expression levels of
      Galectin-3, PAR-1, and MMP-1 in gastric cancer patient tissues and also the
      effects of silencing these proteins with specific siRNAs and of over-expressing
      them using specific lenti-viral constructs. We also employed zebrafish embryo
      model for analysis of in vivo gastric cancer cell invasion. These studies
      demonstrated that: a) galectin-3 silencing decreases the expression of PAR-1. b)
      galectin-3 over-expression increases cell migration and invasion and this
      increase can be reversed by PAR-1 silencing, indicating that galectin-3 increases
      cell migration and invasion via PAR-1 up-regulation. c) galectin-3 directly
      interacts with AP-1 transcriptional factor, and this complex binds to PAR-1
      promoter and drives PAR-1 transcription. d) galectin-3 also amplifies phospho
      paxillin, a PAR-1 downstream target, by increasing MMP-1 expression. MMP-1
      silencing blocks phospho-paxillin amplification and cell invasion caused by
      galectin-3 over-expression. e) Silencing of either galectin-3, PAR-1 or MMP-1
      significantly reduced cell migration into the vessels in zebrafish embryo model.
      f) Galectin-3, PAR-1, and MMP-1 are highly expressed and co-localized in
      malignant tissues from gastric cancer patients. CONCLUSIONS/SIGNIFICANCE:
      Galectin-3 plays the key role of activating cell surface receptor through
      production of protease and boosts gastric cancer metastasis. Galectin-3 has the
      potential to serve as a useful pharmacological target for prevention of gastric
      cancer metastasis.

PMID- 21966429
TI  - Unexpected diversity and photoperiod dependence of the zebrafish melanopsin
      system.
AB  - Animals have evolved specialized photoreceptors in the retina and in extraocular
      tissues that allow them to measure light changes in their environment. In
      mammals, the retina is the only structure that detects light and relays this
      information to the brain. The classical photoreceptors, rods and cones, are
      responsible for vision through activation of rhodopsin and cone opsins.
      Melanopsin, another photopigment first discovered in Xenopus melanophores
      (Opn4x), is expressed in a small subset of retinal ganglion cells (RGCs) in the
      mammalian retina, where it mediates non-image forming functions such as circadian
      photoentrainment and sleep. While mammals have a single melanopsin gene (opn4),
      zebrafish show remarkable diversity with two opn4x-related and three opn4-related
      genes expressed in distinct patterns in multiple neuronal cell types of the
      developing retina, including bipolar interneurons. The intronless opn4.1 gene is
      transcribed in photoreceptors as well as in horizontal cells and produces
      functional photopigment. Four genes are also expressed in the zebrafish embryonic
      brain, but not in the photoreceptive pineal gland. We discovered that photoperiod
      length influences expression of two of the opn4-related genes in retinal layers
      involved in signaling light information to RGCs. Moreover, both genes are
      expressed in a robust diurnal rhythm but with different phases in relation to the
      light-dark cycle. The results suggest that melanopsin has an expanded role in
      modulating the retinal circuitry of fish.

PMID- 21966430
TI  - Gamma-H2AX-based dose estimation for whole and partial body radiation exposure.
AB  - Most human exposures to ionising radiation are partial body exposures. However,
      to date only limited tools are available for rapid and accurate estimation of the
      dose distribution and the extent of the body spared from the exposure. These
      parameters are of great importance for emergency triage and clinical management
      of exposed individuals. Here, measurements of gamma-H2AX immunofluorescence by
      microscopy and flow cytometry were compared as rapid biodosimetric tools for
      whole and partial body exposures. Ex vivo uniformly X-irradiated blood
      lymphocytes from one donor were used to generate a universal biexponential
      calibration function for gamma-H2AX foci/intensity yields per unit dose for time
      points up to 96 hours post exposure. Foci--but not intensity--levels remained
      significantly above background for 96 hours for doses of 0.5 Gy or more. Foci
      based dose estimates for ex vivo X-irradiated blood samples from 13 volunteers
      were in excellent agreement with the actual dose delivered to the targeted
      samples. Flow cytometric dose estimates for X-irradiated blood samples from 8
      volunteers were in excellent agreement with the actual dose delivered at 1 hour
      post exposure but less so at 24 hours post exposure. In partial body exposures,
      simulated by mixing ex vivo irradiated and unirradiated lymphocytes,
      foci/intensity distributions were significantly over-dispersed compared to
      uniformly irradiated lymphocytes. For both methods and in all cases the estimated
      fraction of irradiated lymphocytes and dose to that fraction, calculated using
      the zero contaminated Poisson test and gamma-H2AX calibration function, were in
      good agreement with the actual mixing ratios and doses delivered to the samples.
      In conclusion, gamma-H2AX analysis of irradiated lymphocytes enables rapid and
      accurate assessment of whole body doses while dispersion analysis of foci or
      intensity distributions helps determine partial body doses and the irradiated
      fraction size in cases of partial body exposures.

PMID- 21966431
TI  - No interaction of barrier-to-autointegration factor (BAF) with HIV-1 MA, cone-rod
      homeobox (Crx) or MAN1-C in absence of DNA.
AB  - Barrier-to-autointegration factor is a cellular protein that protects retroviral
      DNA from autointegration. Its cellular role is not well understood, but genetic
      studies show that it is essential and depletion or knockout results in lethal
      nuclear defects. In addition to binding DNA, BAF interacts with the LEM domain, a
      domain shared among a family of lamin-associated polypeptides. BAF has also been
      reported to interact with several other viral and cellular proteins suggesting
      that these interactions may be functionally relevant. We find that, contrary to
      previous reports, BAF does not interact with HIV-1 MA, cone-rod homeobox (Crx) or
      MAN1-C. The reported interactions can be explained by indirect association
      through DNA binding and are unlikely to be biologically relevant. A mutation that
      causes a premature aging syndrome lies on the previously reported MAN1-C binding
      surface of BAF. The absence of direct binding of BAF to MAN1-C eliminates
      disruption of this interaction as the cause of the premature aging phenotype.

PMID- 21966432
TI  - Mitis group streptococci express variable pilus islet 2 pili.
AB  - BACKGROUND: Streptococcus oralis, Streptococcus mitis, and Streptococcus
      sanguinis are members of the Mitis group of streptococci and agents of oral
      biofilm, dental plaque and infective endocarditis, disease processes that involve
      bacteria-bacteria and bacteria-host interactions. Their close relative, the human
      pathogen S. pneumoniae uses pilus-islet 2 (PI-2)-encoded pili to facilitate
      adhesion to eukaryotic cells. METHODOLOGY/PRINCIPAL FINDINGS: PI-2 pilus-encoding
      genetic islets were identified in S. oralis, S. mitis, and S. sanguinis, but were
      absent from other isolates of these species. The PI-2 islets resembled the
      genetic organization of the PI-2 islet of S. pneumoniae, but differed in the
      genes encoding the structural pilus proteins PitA and PitB. Two and three
      variants of pitA (a pseudogene in S. pneumoniae) and pitB, respectively, were
      identified that showed ~20% difference in nucleotide as well as corresponding
      protein sequence. Species-independent combinations of pitA and pitB variants
      indicated prior intra- and interspecies horizontal gene transfer events.
      Polyclonal antisera developed against PitA and PitB of S. oralis type strain
      ATCC35037 revealed that PI-2 pili in oral streptococci were composed of PitA and
      PitB. Electronmicrographs showed pilus structures radiating >700 nm from the
      bacterial surface in the wild type strain, but not in an isogenic PI-2 deletion
      mutant. Anti-PitB-antiserum only reacted with pili containing the same PitB
      variant, whereas anti-PitA antiserum was cross-reactive with the other PitA
      variant. Electronic multilocus sequence analysis revealed that all PI-2-encoding
      oral streptococci were closely-related and cluster with non-PI-2-encoding S.
      oralis strains. CONCLUSIONS/SIGNIFICANCE: This is the first identification of PI
      2 pili in Mitis group oral streptococci. The findings provide a striking example
      of intra- and interspecies horizontal gene transfer. The PI-2 pilus diversity
      provides a possible key to link strain-specific bacterial interactions and/or
      tissue tropisms with pathogenic traits in the Mitis group streptococci.

PMID- 21966433
TI  - Partial inhibition of estrogen-induced mammary carcinogenesis in rats by
      tamoxifen: balance between oxidant stress and estrogen responsiveness.
AB  - Epidemiological and experimental evidences strongly support the role of estrogens
      in breast tumor development. Both estrogen receptor (ER)-dependent and ER
      independent mechanisms are implicated in estrogen-induced breast carcinogenesis.
      Tamoxifen, a selective estrogen receptor modulator is widely used as
      chemoprotectant in human breast cancer. It binds to ERs and interferes with
      normal binding of estrogen to ERs. In the present study, we examined the effect
      of long-term tamoxifen treatment in the prevention of estrogen-induced breast
      cancer. Female ACI rats were treated with 17beta-estradiol (E2), tamoxifen or
      with a combination of E2 and tamoxifen for eight months. Tissue levels of
      oxidative stress markers 8-iso-Prostane F(2alpha) (8-isoPGF(2alpha)), superoxide
      dismutase (SOD), glutathione peroxidase (GPx), catalase, and oxidative DNA damage
      marker 8-hydroxydeoxyguanosine (8-OHdG) were quantified in the mammary tissues of
      all the treatment groups and compared with age-matched controls. Levels of
      tamoxifen metabolizing enzymes cytochrome P450s as well as estrogen responsive
      genes were also quantified. At necropsy, breast tumors were detected in 44% of
      rats co-treated with tamoxifen+E2. No tumors were detected in the sham or
      tamoxifen only treatment groups whereas in the E2 only treatment group, the tumor
      incidence was 82%. Co-treatment with tamoxifen decreased GPx and catalase levels;
      did not completely inhibit E2-mediated oxidative DNA damage and estrogen
      responsive genes monoamine oxygenase B1 (MaoB1) and cell death inducing DFF45
      like effector C (Cidec) but differentially affected the levels of tamoxifen
      metabolizing enzymes. In summary, our studies suggest that although tamoxifen
      treatment inhibits estrogen-induced breast tumor development and increases the
      latency of tumor development, it does not completely abrogate breast tumor
      development in a rat model of estrogen-induced breast cancer. The inability of
      tamoxifen to completely inhibit E2-induced breast carcinogenesis may be because
      of increased estrogen-mediated oxidant burden.

PMID- 21966434
TI  - Transplacentally acquired maternal antibody against hepatitis B surface antigen
      in infants and its influence on the response to hepatitis B vaccine.
AB  - BACKGROUND: Passively acquired maternal antibodies in infants may inhibit active
      immune responses to vaccines. Whether maternal antibody against hepatitis B
      surface antigen (anti-HBs) in infants may influence the long-term immunogenicity
      of hepatitis B vaccine remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: Totally
      338 pairs of mothers and children were enrolled. All infants were routinely
      vaccinated against hepatitis B based on 0-, 1- and 6-month schedule. We
      characterized the transplacental transfer of maternal anti-HBs, and compared anti
      HBs response in children of mothers with or without anti-HBs. In a prospective
      observation, all 63 anti-HBs positive mothers transferred anti-HBs to their
      infants; 84.1% of the infants had higher anti-HBs concentrations than their
      mothers. One and half years after vaccination with three doses of hepatitis B
      vaccine, the positive rate and geometric mean concentration (GMC) of anti-HBs in
      32 infants with maternal anti-HBs were comparable with those in 32 infants
      without maternal antibody (90.6% vs 87.5%, P = 0.688, and 74.5 vs 73.5 mIU/ml, P
      = 0.742, respectively). In a retrospective analysis, five and half years after
      vaccination with three doses vaccine, the positive rates of anti-HBs in 88
      children of mothers with anti-HBs >=1000 mIU/ml, 94 children of mothers with anti
      HBs 10-999 mIU/ml, and 61 children of mothers with anti-HBs <10 mIU/ml were
      72.7%, 69.2%, and 63.9% (P = 0.521), respectively; anti-HBs GMC in these three
      groups were 38.9, 43.9, and 31.7 mIU/ml (P = 0.726), respectively.
      CONCLUSIONS/SIGNIFICANCE: The data demonstrate that maternal anti-HBs in infants,
      even at high concentrations, does not inhibit the long-term immunogenicity of
      hepatitis B vaccine. Thus, current hepatitis B vaccination schedule for infants
      will be still effective in the future when most infants are positive for maternal
      anti-HBs due to the massive vaccination against hepatitis B.

PMID- 21966436
TI  - Causes and consequences of past and projected Scandinavian summer temperatures,
      500-2100 AD.
AB  - Tree rings dominate millennium-long temperature reconstructions and many records
      originate from Scandinavia, an area for which the relative roles of external
      forcing and internal variation on climatic changes are, however, not yet fully
      understood. Here we compile 1,179 series of maximum latewood density measurements
      from 25 conifer sites in northern Scandinavia, establish a suite of 36 subset
      chronologies, and analyse their climate signal. A new reconstruction for the 1483
      2006 period correlates at 0.80 with June-August temperatures back to 1860. Summer
      cooling during the early 17th century and peak warming in the 1930s translate
      into a decadal amplitude of 2.9 degrees C, which agrees with existing
      Scandinavian tree-ring proxies. Climate model simulations reveal similar amounts
      of mid to low frequency variability, suggesting that internal ocean-atmosphere
      feedbacks likely influenced Scandinavian temperatures more than external forcing.
      Projected 21st century warming under the SRES A2 scenario would, however, exceed
      the reconstructed temperature envelope of the past 1,500 years.

PMID- 21966435
TI  - The dual PI3K/mTOR inhibitor NVP-BEZ235 induces tumor regression in a genetically
      engineered mouse model of PIK3CA wild-type colorectal cancer.
AB  - PURPOSE: To examine the in vitro and in vivo efficacy of the dual PI3K/mTOR
      inhibitor NVP-BEZ235 in treatment of PIK3CA wild-type colorectal cancer (CRC).
      EXPERIMENTAL DESIGN: PIK3CA mutant and wild-type human CRC cell lines were
      treated in vitro with NVP-BEZ235, and the resulting effects on proliferation,
      apoptosis, and signaling were assessed. Colonic tumors from a genetically
      engineered mouse (GEM) model for sporadic wild-type PIK3CA CRC were treated in
      vivo with NVP-BEZ235. The resulting effects on macroscopic tumor
      growth/regression, proliferation, apoptosis, angiogenesis, and signaling were
      examined. RESULTS: In vitro treatment of CRC cell lines with NVP-BEZ235 resulted
      in transient PI3K blockade, sustained decreases in mTORC1/mTORC2 signaling, and a
      corresponding decrease in cell viability (median IC(50) = 9.0-14.3 nM). Similar
      effects were seen in paired isogenic CRC cell lines that differed only in the
      presence or absence of an activating PIK3CA mutant allele. In vivo treatment of
      colonic tumor-bearing mice with NVP-BEZ235 resulted in transient PI3K inhibition
      and sustained blockade of mTORC1/mTORC2 signaling. Longitudinal tumor
      surveillance by optical colonoscopy demonstrated a 97% increase in tumor size in
      control mice (p = 0.01) vs. a 43% decrease (p = 0.008) in treated mice. Ex vivo
      analysis of the NVP-BEZ235-treated tumors demonstrated a 56% decrease in
      proliferation (p = 0.003), no effects on apoptosis, and a 75% reduction in
      angiogenesis (p = 0.013). CONCLUSIONS: These studies provide the preclinical
      rationale for studies examining the efficacy of the dual PI3K/mTOR inhibitor NVP
      BEZ235 in treatment of PIK3CA wild-type CRC.

PMID- 21966437
TI  - Accelerated CCl4-induced liver fibrosis in Hjv-/- mice, associated with an
      oxidative burst and precocious profibrogenic gene expression.
AB  - Hereditary hemochromatosis is commonly associated with liver fibrosis. Likewise,
      hepatic iron overload secondary to chronic liver diseases aggravates liver
      injury. To uncover underlying molecular mechanisms, hemochromatotic hemojuvelin
      knockout (Hjv-/-) mice and wild type (wt) controls were intoxicated with CCl(4).
      Hjv-/- mice developed earlier (by 2-4 weeks) and more acute liver damage,
      reflected in dramatic levels of serum transaminases and ferritin and the
      development of severe coagulative necrosis and fibrosis. These responses were
      associated with an oxidative burst and early upregulation of mRNAs encoding
      alpha1-(I)-collagen, the profibrogenic cytokines TGF-beta1, endothelin-1 and PDGF
      and, notably, the iron-regulatory hormone hepcidin. Hence, CCl4-induced liver
      fibrogenesis was exacerbated and progressed precociously in Hjv-/- animals. Even
      though livers of naive Hjv-/- mice were devoid of apparent pathology, they
      exhibited oxidative stress and immunoreactivity towards alpha-SMA antibodies, a
      marker of hepatic stellate cells activation. Furthermore, they expressed
      significantly higher (2-3 fold vs. wt, p<0.05) levels of alpha1-(I)-collagen, TGF
      beta1, endothelin-1 and PDGF mRNAs, indicative of early fibrogenesis. Our data
      suggest that hepatic iron overload in parenchymal cells promotes oxidative stress
      and triggers premature profibrogenic gene expression, contributing to accelerated
      onset and precipitous progression of liver fibrogenesis.

PMID- 21966438
TI  - Assessing historical fish community composition using surveys, historical
      collection data, and species distribution models.
AB  - Accurate establishment of baseline conditions is critical to successful
      management and habitat restoration. We demonstrate the ability to robustly
      estimate historical fish community composition and assess the current status of
      the urbanized Barton Creek watershed in central Texas, U.S.A. Fish species were
      surveyed in 2008 and the resulting data compared to three sources of fish
      occurrence information: (i) historical records from a museum specimen database
      and literature searches; (ii) a nearly identical survey conducted 15 years
      earlier; and (iii) a modeled historical community constructed with species
      distribution models (SDMs). This holistic approach, and especially the
      application of SDMs, allowed us to discover that the fish community in Barton
      Creek was more diverse than the historical data and survey methods alone
      indicated. Sixteen native species with high modeled probability of occurrence
      within the watershed were not found in the 2008 survey, seven of these were not
      found in either survey or in any of the historical collection records. Our
      approach allowed us to more rigorously establish the true baseline for the pre
      development fish fauna and then to more accurately assess trends and develop
      hypotheses regarding factors driving current fish community composition to better
      inform management decisions and future restoration efforts. Smaller, urbanized
      freshwater systems, like Barton Creek, typically have a relatively poor
      historical biodiversity inventory coupled with long histories of alteration, and
      thus there is a propensity for land managers and researchers to apply inaccurate
      baseline standards. Our methods provide a way around that limitation by using
      SDMs derived from larger and richer biodiversity databases of a broader
      geographic scope. Broadly applied, we propose that this technique has potential
      to overcome limitations of popular bioassessment metrics (e.g., IBI) to become a
      versatile and robust management tool for determining status of freshwater biotic
      communities.

PMID- 21966439
TI  - Comparing effectiveness of top-down and bottom-up strategies in containing
      influenza.
AB  - This research compares the performance of bottom-up, self-motivated behavioral
      interventions with top-down interventions targeted at controlling an "Influenza
      like-illness". Both types of interventions use a variant of the ring strategy. In
      the first case, when the fraction of a person's direct contacts who are diagnosed
      exceeds a threshold, that person decides to seek prophylaxis, e.g. vaccine or
      antivirals; in the second case, we consider two intervention protocols, denoted
      Block and School: when a fraction of people who are diagnosed in a Census Block
      (resp., School) exceeds the threshold, prophylax the entire Block (resp.,
      School). Results show that the bottom-up strategy outperforms the top-down
      strategies under our parameter settings. Even in situations where the Block
      strategy reduces the overall attack rate well, it incurs a much higher cost.
      These findings lend credence to the notion that if people used antivirals
      effectively, making them available quickly on demand to private citizens could be
      a very effective way to control an outbreak.

PMID- 21966440
TI  - Exploring DNA topoisomerase I ligand space in search of novel anticancer agents.
AB  - DNA topoisomerase I (Top1) is over-expressed in tumour cells and is an important
      target in cancer chemotherapy. It relaxes DNA torsional strain generated during
      DNA processing by introducing transient single-strand breaks and allowing the
      broken strand to rotate around the intermediate Top1-DNA covalent complex. This
      complex can be trapped by a group of anticancer agents interacting with the DNA
      bases and the enzyme at the cleavage site, preventing further topoisomerase
      activity. Here we have identified novel Top1 inhibitors as potential anticancer
      agents by using a combination of structure- and ligand-based molecular modelling
      methods. Pharmacophore models have been developed based on the molecular
      characteristics of derivatives of the alkaloid camptothecin (CPT), which
      represent potent antitumour agents and the main group of Top1 inhibitors. The
      models generated were used for in silico screening of the National Cancer
      Institute (NCI, USA) compound database, leading to the identification of a set of
      structurally diverse molecules. The strategy is validated by the observation that
      amongst these molecules are several known Top1 inhibitors and agents cytotoxic
      against human tumour cell lines. The potential of the untested hits to inhibit
      Top1 activity was further evaluated by docking into the binding site of a Top1
      DNA complex, resulting in a selection of 10 compounds for biological testing.
      Limited by the compound availability, 7 compounds have been tested in vitro for
      their Top1 inhibitory activity, 5 of which display mild to moderate Top1
      inhibition. A further compound, found by similarity search to the active
      compounds, also shows mild activity. Although the tested compounds display only
      low in vitro antitumour activity, our approach has been successful in the
      identification of structurally novel Top1 inhibitors worthy of further
      investigation as potential anticancer agents.

PMID- 21966441
TI  - A fasciclin-like arabinogalactan-protein (FLA) mutant of Arabidopsis thaliana,
      fla1, shows defects in shoot regeneration.
AB  - BACKGROUND: The fasciclin-like arabinogalactan-proteins (FLAs) are an enigmatic
      class of 21 members within the larger family of arabinogalactan-proteins (AGPs)
      in Arabidopsis thaliana. Located at the cell surface, in the cell wall/plasma
      membrane, they are implicated in many developmental roles yet their function
      remains largely undefined. Fasciclin (FAS) domains are putative cell-adhesion
      domains found in extracellular matrix proteins of organisms from all kingdoms,
      but the juxtaposition of FAS domains with highly glycosylated AGP domains is
      unique to plants. Recent studies have started to elucidate the role of FLAs in
      Arabidopsis development. FLAs containing a single FAS domain are important for
      the integrity and elasticity of the plant cell wall matrix (FLA11 and FLA12) and
      FLA3 is involved in microspore development. FLA4/SOS5 with two FAS domains and
      two AGP domains has a role in maintaining proper cell expansion under salt
      stressed conditions. The role of other FLAs remains to be uncovered.
      METHOD/PRINCIPAL FINDINGS: Here we describe the characterisation of a T-DNA
      insertion mutant in the FLA1 gene (At5g55730). Under standard growth conditions
      fla1-1 mutants have no obvious phenotype. Based on gene expression studies, a
      putative role for FLA1 in callus induction was investigated and revealed that
      fla1-1 has a reduced ability to regenerate shoots in an in vitro shoot-induction
      assay. Analysis of FLA1p:GUS reporter lines show that FLA1 is expressed in
      several tissues including stomata, trichomes, the vasculature of leaves, the
      primary root tip and in lateral roots near the junction of the primary root.
      CONCLUSION: The results of the developmental expression of FLA1 and
      characterisation of the fla1 mutant support a role for FLA1 in the early events
      of lateral root development and shoot development in tissue culture, prior to
      cell-type specification.

PMID- 21966442
TI  - Green sturgeon physical habitat use in the coastal Pacific Ocean.
AB  - The green sturgeon (Acipenser medirostris) is a highly migratory, oceanic,
      anadromous species with a complex life history that makes it vulnerable to
      species-wide threats in both freshwater and at sea. Green sturgeon population
      declines have preceded legal protection and curtailment of activities in marine
      environments deemed to increase its extinction risk. Yet, its marine habitat is
      poorly understood. We built a statistical model to characterize green sturgeon
      marine habitat using data from a coastal tracking array located along the Siletz
      Reef near Newport, Oregon, USA that recorded the passage of 37 acoustically
      tagged green sturgeon. We classified seafloor physical habitat features with high
      resolution bathymetric and backscatter data. We then described the distribution
      of habitat components and their relationship to green sturgeon presence using
      ordination and subsequently used generalized linear model selection to identify
      important habitat components. Finally, we summarized depth and temperature
      recordings from seven green sturgeon present off the Oregon coast that were
      fitted with pop-off archival geolocation tags. Our analyses indicated that green
      sturgeon, on average, spent a longer duration in areas with high seafloor
      complexity, especially where a greater proportion of the substrate consists of
      boulders. Green sturgeon in marine habitats are primarily found at depths of 20
      60 meters and from 9.5-16.0 degrees C. Many sturgeon in this study were likely
      migrating in a northward direction, moving deeper, and may have been using
      complex seafloor habitat because it coincides with the distribution of benthic
      prey taxa or provides refuge from predators. Identifying important green sturgeon
      marine habitat is an essential step towards accurately defining the conditions
      that are necessary for its survival and will eventually yield range-wide,
      spatially explicit predictions of green sturgeon distribution.

PMID- 21966443
TI  - Identification of novel Pax8 targets in FRTL-5 thyroid cells by gene silencing
      and expression microarray analysis.
AB  - BACKGROUND: The differentiation program of thyroid follicular cells (TFCs), by
      far the most abundant cell population of the thyroid gland, relies on the
      interplay between sequence-specific transcription factors and transcriptional
      coregulators with the basal transcriptional machinery of the cell. However, the
      molecular mechanisms leading to the fully differentiated thyrocyte are still the
      object of intense study. The transcription factor Pax8, a member of the Paired
      box gene family, has been demonstrated to be a critical regulator required for
      proper development and differentiation of thyroid follicular cells. Despite being
      Pax8 well-characterized with respect to its role in regulating genes involved in
      thyroid differentiation, genomics approaches aiming at the identification of
      additional Pax8 targets are lacking and the biological pathways controlled by
      this transcription factor are largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: To
      identify unique downstream targets of Pax8, we investigated the genome-wide
      effect of Pax8 silencing comparing the transcriptome of silenced versus normal
      differentiated FRTL-5 thyroid cells. In total, 2815 genes were found modulated 72
      h after Pax8 RNAi, induced or repressed. Genes previously reported to be
      regulated by Pax8 in FRTL-5 cells were confirmed. In addition, novel targets
      genes involved in functional processes such as DNA replication, anion transport,
      kinase activity, apoptosis and cellular processes were newly identified.
      Transcriptome analysis highlighted that Pax8 is a key molecule for thyroid
      morphogenesis and differentiation. CONCLUSIONS/SIGNIFICANCE: This is the first
      large-scale study aimed at the identification of new genes regulated by Pax8, a
      master regulator of thyroid development and differentiation. The biological
      pathways and target genes controlled by Pax8 will have considerable importance to
      understand thyroid disease progression as well as to set up novel therapeutic
      strategies.

PMID- 21966444
TI  - Chronic consumption of farmed salmon containing persistent organic pollutants
      causes insulin resistance and obesity in mice.
AB  - BACKGROUND: Dietary interventions are critical in the prevention of metabolic
      diseases. Yet, the effects of fatty fish consumption on type 2 diabetes remain
      unclear. The aim of this study was to investigate whether a diet containing
      farmed salmon prevents or contributes to insulin resistance in mice.
      METHODOLOGY/PRINCIPAL FINDINGS: Adult male C57BL/6J mice were fed control diet
      (C), a very high-fat diet without or with farmed Atlantic salmon fillet (VHF and
      VHF/S, respectively), and Western diet without or with farmed Atlantic salmon
      fillet (WD and WD/S, respectively). Other mice were fed VHF containing farmed
      salmon fillet with reduced concentrations of persistent organic pollutants
      (VHF/S(-POPs)). We assessed body weight gain, fat mass, insulin sensitivity,
      glucose tolerance, ex vivo muscle glucose uptake, performed histology and
      immunohistochemistry analysis, and investigated gene and protein expression. In
      comparison with animals fed VHF and WD, consumption of both VHF/S and WD/S
      exaggerated insulin resistance, visceral obesity, and glucose intolerance. In
      addition, the ability of insulin to stimulate Akt phosphorylation and muscle
      glucose uptake was impaired in mice fed farmed salmon. Relative to VHF/S-fed
      mice, animals fed VHF/S(-POPs) had less body burdens of POPs, accumulated less
      visceral fat, and had reduced mRNA levels of TNFalpha as well as macrophage
      infiltration in adipose tissue. VHF/S(-POPs)-fed mice further exhibited better
      insulin sensitivity and glucose tolerance than mice fed VHF/S.
      CONCLUSIONS/SIGNIFICANCE: Our data indicate that intake of farmed salmon fillet
      contributes to several metabolic disorders linked to type 2 diabetes and obesity,
      and suggest a role of POPs in these deleterious effects. Overall, these findings
      may participate to improve nutritional strategies for the prevention and therapy
      of insulin resistance.

PMID- 21966445
TI  - Quantitative historical change in bumblebee (Bombus spp.) assemblages of red
      clover fields.
AB  - BACKGROUND: Flower visiting insects provide a vitally important pollination
      service for many crops and wild plants. Recent decline of pollinating insects due
      to anthropogenic modification of habitats and climate, in particular from 1950's
      onwards, is a major and widespread concern. However, few studies document the
      extent of declines in species diversity, and no studies have previously
      quantified local abundance declines. We here make a quantitative assessment of
      recent historical changes in bumblebee assemblages by comparing contemporary and
      historical survey data. METHODOLOGY/PRINCIPAL FINDINGS: We take advantage of
      detailed, quantitative historical survey data from the 1930's on bumblebee
      (Bombus spp.) abundances and species composition in red clover (Trifolium
      pratense) fields, an important floral resource and an attractant of all bumblebee
      species. We used the historical survey data as a pre-industrialization baseline,
      and repeated the same sampling protocol at nearly the same localities at present,
      hence setting up a historical experiment. We detected historical changes in
      abundances (bees/m(2)) of both workers (the "pollinatory units") and queens
      (effective population size), in addition to species composition. In particular,
      long-tongued bumblebee species showed consistent and dramatic declines in species
      richness and abundances throughout the flowering season of red clover, while
      short-tongued species were largely unaffected. Of 12 Bombus species observed in
      the 1930's, five species were not observed at present. The latter were all long
      tongued, late-emerging species. CONCLUSIONS/SIGNIFICANCE: Because bumblebees are
      important pollinators, historical changes in local bumblebee assemblages are
      expected to severely affect plant reproduction, in particular long-tubed species,
      which are pollinated by long-tongued bumblebees.

PMID- 21966446
TI  - Substrate type determines metagenomic profiles from diverse chemical habitats.
AB  - Environmental parameters drive phenotypic and genotypic frequency variations in
      microbial communities and thus control the extent and structure of microbial
      diversity. We tested the extent to which microbial community composition changes
      are controlled by shifting physiochemical properties within a hypersaline lagoon.
      We sequenced four sediment metagenomes from the Coorong, South Australia from
      samples which varied in salinity by 99 Practical Salinity Units (PSU), an order
      of magnitude in ammonia concentration and two orders of magnitude in microbial
      abundance. Despite the marked divergence in environmental parameters observed
      between samples, hierarchical clustering of taxonomic and metabolic profiles of
      these metagenomes showed striking similarity between the samples (>89%).
      Comparison of these profiles to those derived from a wide variety of publically
      available datasets demonstrated that the Coorong sediment metagenomes were
      similar to other sediment, soil, biofilm and microbial mat samples regardless of
      salinity (>85% similarity). Overall, clustering of solid substrate and water
      metagenomes into discrete similarity groups based on functional potential
      indicated that the dichotomy between water and solid matrices is a fundamental
      determinant of community microbial metabolism that is not masked by salinity,
      nutrient concentration or microbial abundance.

PMID- 21966447
TI  - Temporal regulation of rapamycin on memory CTL programming by IL-12.
AB  - Mammalian target of rapamycin (mTOR) is a master regulator of cell growth. Recent
      reports have defined its important role in memory cytotoxic T lymphocyte (CTL)
      differentiation in infections and memory programming. We report that rapamycin
      regulated memory CTL programming by IL-12 to a similar level in a wide range of
      concentrations, and the enhanced memory CTLs by rapamycin were functional and
      provided similar protection against Listeria Monocytogenes challenge compared to
      the control. In addition, rapamycin-experienced CTLs went through substantially
      enhanced proliferation after transfer into recipients. Furthermore, the
      regulatory function of rapamycin on CD62L expression in memory CTLs was mainly
      contributed by the presence of rapamycin in the first 24-hr of stimulation in
      vitro, whereas the effective window of rapamycin on the size of memory CTLs was
      determined between 24 to 72 hrs. In conclusion, rapamycin regulates IL-12-driven
      programming of CTLs to a similar level in a wide range of concentrations, and
      regulates the phenotype and the size of memory CTLs in different temporal
      windows.

PMID- 21966448
TI  - Surgery versus watchful waiting in patients with craniofacial fibrous dysplasia-
      a meta-analysis.
AB  - BACKGROUND: Fibrous dysplasia (FD) is a benign bone tumor which most commonly
      involves the craniofacial skeleton. The most devastating consequence of
      craniofacial FD (CFD) is loss of vision due to optic nerve compression (ONC).
      Radiological evidence of ONC is common, however the management of this condition
      is not well established. Our objective was to compare the long-term outcome of
      patients with optic nerve compression (ONC) due to craniofacial fibrous dysplasia
      (CFD) who either underwent surgery or were managed expectantly.
      METHODOLOGY/PRINCIPAL FINDINGS: We performed a meta-analysis of 27 studies along
      with analysis of the records of a cohort of patients enrolled in National
      Institutes of Health (NIH) protocol 98-D-0145, entitled Screening and Natural
      History of Fibrous Dysplasia, with a diagnosis of CFD. The study group consisted
      of 241 patients; 122 were enrolled in the NIH study and 119 were extracted from
      cases published in the literature. The median follow-up period was 54 months
      (range, 6-228 months). A total of 368 optic nerves were investigated. All
      clinically impaired optic nerves (n = 86, 23.3%) underwent therapeutic
      decompression. Of the 282 clinically intact nerves, 41 (15%) were surgically
      decompressed and 241 (85%) were followed expectantly. Improvement in visual
      function was reported in fifty-eight (67.4%) of the clinically impaired nerves
      after surgery. In the intact nerves group, long-term stable vision was achieved
      in 31/45 (75.6%) of the operated nerves, compared to 229/241 (95.1%) of the non
      operated ones (p = 0.0003). Surgery in asymptomatic patients was associated with
      visual deterioration (RR 4.89; 95% CI 2.26-10.59). CONCLUSIONS: Most patients
      with CFD will remain asymptomatic during long-term follow-up. Expectant
      management is recommended in asymptomatic patients even in the presence of
      radiological evidence of ONC.

PMID- 21966449
TI  - High-throughput analysis of promoter occupancy reveals new targets for Arx, a
      gene mutated in mental retardation and interneuronopathies.
AB  - Genetic investigations of X-linked intellectual disabilities have implicated the
      ARX (Aristaless-related homeobox) gene in a wide spectrum of disorders extending
      from phenotypes characterised by severe neuronal migration defects such as
      lissencephaly, to mild or moderate forms of mental retardation without apparent
      brain abnormalities but with associated features of dystonia and epilepsy.
      Analysis of Arx spatio-temporal localisation profile in mouse revealed expression
      in telencephalic structures, mainly restricted to populations of GABAergic
      neurons at all stages of development. Furthermore, studies of the effects of ARX
      loss of function in humans and animal models revealed varying defects, suggesting
      multiple roles of this gene during brain development. However, to date, little is
      known about how ARX functions as a transcription factor and the nature of its
      targets. To better understand its role, we combined chromatin immunoprecipitation
      and mRNA expression with microarray analysis and identified a total of 1006 gene
      promoters bound by Arx in transfected neuroblastoma (N2a) cells and in mouse
      embryonic brain. Approximately 24% of Arx-bound genes were found to show
      expression changes following Arx overexpression or knock-down. Several of the Arx
      target genes we identified are known to be important for a variety of functions
      in brain development and some of them suggest new functions for Arx. Overall,
      these results identified multiple new candidate targets for Arx and should help
      to better understand the pathophysiological mechanisms of intellectual disability
      and epilepsy associated with ARX mutations.

PMID- 21966450
TI  - High level of soluble HLA-G in the female genital tract of Beninese commercial
      sex workers is associated with HIV-1 infection.
AB  - BACKGROUND: Most HIV infections are transmitted across mucosal epithelium.
      Understanding the role of innate and specific mucosal immunity in susceptibility
      or protection against HIV infection, as well as the effect of HIV infection on
      mucosal immunity, are of fundamental importance. HLA-G is a powerful modulator of
      the immune response. The aim of this study was to investigate whether soluble HLA
      G (sHLA-G) expression in the female genital tract is associated with HIV-1
      infection. METHODS AND FINDINGS: Genital levels of sHLA-G were determined in 52
      HIV-1-uninfected and 44 antiretroviral naive HIV-1-infected female commercial sex
      workers (CSWs), as well as 71 HIV-1-uninfected non-CSW women at low risk of
      exposure, recruited in Cotonou, Benin. HIV-1-infected CSWs had higher genital
      levels of sHLA-G compared with those in both the HIV-1-uninfected CSW (P = 0.009)
      and non-CSW groups (P = 0.0006). The presence of bacterial vaginosis (P = 0.008),
      and HLA-G*01:01:02 genotype (P = 0.002) were associated with higher genital
      levels of sHLA-G in the HIV-1-infected CSWs, whereas the HLA-G*01:04:04 genotype
      was also associated with higher genital level of sHLA-G in the overall population
      (P = 0.038). When adjustment was made for all significant variables, the
      increased expression of sHLA-G in the genital mucosa remained significantly
      associated with both HIV-1 infection (P = 0.02) and bacterial vaginosis (P =
      0.03). CONCLUSION: This study demonstrates that high level of sHLA-G in the
      genital mucosa is independently associated with both HIV-1 infection and
      bacterial vaginosis.

PMID- 21966451
TI  - Repression of androgen receptor transcription through the E2F1/DNMT1 axis.
AB  - Although androgen receptor (AR) function has been extensively studied, regulation
      of the AR gene itself has been much less characterized. In this study, we
      observed a dramatic reduction in the expression of androgen receptor mRNA and
      protein in hyperproliferative prostate epithelium of keratin 5 promoter driven
      E2F1 transgenic mice. To confirm an inhibitory function for E2F1 on AR
      transcription, we showed that E2F1 inhibited the transcription of endogenous AR
      mRNA, subsequent AR protein, and AR promoter activity in both human and mouse
      epithelial cells. E2F1 also inhibited androgen-stimulated activation of two AR
      target gene promoters. To elucidate the molecular mechanism of E2F-mediated
      inhibition of AR, we evaluated the effects of two functional E2F1 mutants on AR
      promoter activity and found that the transactivation domain appears to mediate
      E2F1 repression of the AR promoter. Because DNMT1 is a functional intermediate of
      E2F1 we examined DNMT1 function in AR repression. Repression of endogenous AR in
      normal human prostate epithelial cells was relieved by DNMT1 shRNA knock down.
      DNMT1 was shown to be physically associated within the AR minimal promoter
      located 22 bps from the transcription start site; however, methylation remained
      unchanged at the promoter regardless of DNMT1 expression. Taken together, our
      results suggest that DNMT1 operates either as a functional intermediary or in
      cooperation with E2F1 inhibiting AR gene expression in a methylation independent
      manner.

PMID- 21966453
TI  - Arachidonic acid randomizes endothelial cell motion and regulates adhesion and
      migration.
AB  - Cell adhesion and migration are essential for the evolution, organization, and
      repair of living organisms. An example of a combination of these processes is the
      formation of new blood vessels (angiogenesis), which is mediated by a directed
      migration and adhesion of endothelial cells (ECs). Angiogenesis is an essential
      part of wound healing and a prerequisite of cancerous tumor growth. We
      investigated the effect of the amphiphilic compound arachidonic acid (AA) on EC
      adhesion and migration by combining live cell imaging with biophysical analysis
      methods. AA significantly influenced both EC adhesion and migration, in either a
      stimulating or inhibiting fashion depending on AA concentration. The temporal
      evolution of cell adhesion area was well described by a two-phase model. In the
      first phase, the spreading dynamics were independent of AA concentration. In the
      latter phase, the spreading dynamics increased at low AA concentrations and
      decreased at high AA concentrations. AA also affected EC migration; though the
      instantaneous speed of individual cells remained independent of AA concentration,
      the individual cells lost their sense of direction upon addition of AA, thus
      giving rise to an overall decrease in the collective motion of a confluent EC
      monolayer into vacant space. Addition of AA also caused ECs to become more
      elongated, this possibly being related to incorporation of AA in the EC membrane
      thus mediating a change in the viscosity of the membrane. Hence, AA is a
      promising non-receptor specific regulator of wound healing and angiogenesis.

PMID- 21966452
TI  - Developmental patterns of doublecortin expression and white matter neuron density
      in the postnatal primate prefrontal cortex and schizophrenia.
AB  - Postnatal neurogenesis occurs in the subventricular zone and dentate gyrus, and
      evidence suggests that new neurons may be present in additional regions of the
      mature primate brain, including the prefrontal cortex (PFC). Addition of new
      neurons to the PFC implies local generation of neurons or migration from areas
      such as the subventricular zone. We examined the putative contribution of new,
      migrating neurons to postnatal cortical development by determining the density of
      neurons in white matter subjacent to the cortex and measuring expression of
      doublecortin (DCX), a microtubule-associated protein involved in neuronal
      migration, in humans and rhesus macaques. We found a striking decline in DCX
      expression (human and macaque) and density of white matter neurons (humans)
      during infancy, consistent with the arrival of new neurons in the early postnatal
      cortex. Considering the expansion of the brain during this time, the decline in
      white matter neuron density does not necessarily indicate reduced total numbers
      of white matter neurons in early postnatal life. Furthermore, numerous cells in
      the white matter and deep grey matter were positive for the migration-associated
      glycoprotein polysialiated-neuronal cell adhesion molecule and GAD65/67,
      suggesting that immature migrating neurons in the adult may be GABAergic. We also
      examined DCX mRNA in the PFC of adult schizophrenia patients (n = 37) and matched
      controls (n = 37) and did not find any difference in DCX mRNA expression.
      However, we report a negative correlation between DCX mRNA expression and white
      matter neuron density in adult schizophrenia patients, in contrast to a positive
      correlation in human development where DCX mRNA and white matter neuron density
      are higher earlier in life. Accumulation of neurons in the white matter in
      schizophrenia would be congruent with a negative correlation between DCX mRNA and
      white matter neuron density and support the hypothesis of a migration deficit in
      schizophrenia.

PMID- 21966454
TI  - Barcoded pyrosequencing reveals that consumption of galactooligosaccharides
      results in a highly specific bifidogenic response in humans.
AB  - Prebiotics are selectively fermented ingredients that allow specific changes in
      the gastrointestinal microbiota that confer health benefits to the host. However,
      the effects of prebiotics on the human gut microbiota are incomplete as most
      studies have relied on methods that fail to cover the breadth of the bacterial
      community. The goal of this research was to use high throughput multiplex
      community sequencing of 16S rDNA tags to gain a community wide perspective of the
      impact of prebiotic galactooligosaccharide (GOS) on the fecal microbiota of
      healthy human subjects. Fecal samples from eighteen healthy adults were
      previously obtained during a feeding trial in which each subject consumed a GOS
      containing product for twelve weeks, with four increasing dosages (0, 2.5, 5, and
      10 gram) of GOS. Multiplex sequencing of the 16S rDNA tags revealed that GOS
      induced significant compositional alterations in the fecal microbiota,
      principally by increasing the abundance of organisms within the Actinobacteria.
      Specifically, several distinct lineages of Bifidobacterium were enriched.
      Consumption of GOS led to five- to ten-fold increases in bifidobacteria in half
      of the subjects. Increases in Firmicutes were also observed, however, these
      changes were detectable in only a few individuals. The enrichment of
      bifidobacteria was generally at the expense of one group of bacteria, the
      Bacteroides. The responses to GOS and the magnitude of the response varied
      between individuals, were reversible, and were in accordance with dosage. The
      bifidobacteria were the only bacteria that were consistently and significantly
      enriched by GOS, although this substrate supported the growth of diverse colonic
      bacteria in mono-culture experiments. These results suggest that GOS can be used
      to enrich bifidobacteria in the human gastrointestinal tract with remarkable
      specificity, and that the bifidogenic properties of GOS that occur in vivo are
      caused by selective fermentation as well as by competitive interactions within
      the intestinal environment.

PMID- 21966455
TI  - Intrinsic mitochondrial membrane potential and associated tumor phenotype are
      independent of MUC1 over-expression.
AB  - We have established previously that minor subpopulations of cells with stable
      differences in their intrinsic mitochondrial membrane potential (Deltapsim) exist
      within populations of mammary and colonic carcinoma cells and that these
      differences in Deltapsim are linked to tumorigenic phenotypes consistent with
      increased probability of participating in tumor progression. However, the
      mechanism(s) involved in generating and maintaining stable differences in
      intrinsic Deltapsim and how they are linked to phenotype are unclear. Because the
      mucin 1 (MUC1) oncoprotein is over-expressed in many cancers, with the
      cytoplasmic C-terminal fragment (MUC1 C-ter) and its integration into the outer
      mitochondrial membrane linked to tumorigenic phenotypes similar to those of cells
      with elevated intrinsic Deltapsim, we investigated whether endogenous differences
      in MUC1 levels were linked to stable differences in intrinsic Deltapsim and/or to
      the tumor phenotypes associated with the intrinsic Deltapsim. We report that
      levels of MUC1 are significantly higher in subpopulations of cells with elevated
      intrinsic Deltapsim derived from both mammary and colonic carcinoma cell lines.
      However, using siRNA we found that down-regulation of MUC1 failed to
      significantly affect either the intrinsic Deltapsim or the tumor phenotypes
      associated with increased intrinsic Deltapsim. Moreover, whereas
      pharmacologically mediated disruption of the Deltapsim was accompanied by
      attenuation of tumor phenotype, it had no impact on MUC1 levels. Therefore, while
      MUC1 over-expression is associated with subpopulations of cells with elevated
      intrinsic Deltapsim, it is not directly linked to the generation or maintenance
      of stable alterations in intrinsic Deltapsim, or to intrinsic Deltapsim
      associated tumor phenotypes. Since the Deltapsim is the focus of chemotherapeutic
      strategies, these data have important clinical implications in regard to
      effectively targeting those cells within a tumor cell population that exhibit
      stable elevations in intrinsic Deltapsim and are most likely to contribute to
      tumor progression.

PMID- 21966456
TI  - Prostaglandin E receptor subtype EP3 expression in human conjunctival epithelium
      and its changes in various ocular surface disorders.
AB  - BACKGROUND: In our earlier genome-wide association study on Stevens-Johnson
      Syndrome (SJS) and its severe variant, toxic epidermal necrolysis (TEN), we found
      that in Japanese patients with these severe ocular surface complications there
      was an association with prostaglandin E receptor 3 (EP3) gene (PTGER3)
      polymorphisms. We also reported that EP3 is dominantly expressed in the ocular
      surface-, especially the conjunctival epithelium, and suggested that EP3 in the
      conjunctival epithelium may down-regulate ocular surface inflammation. In the
      current study we investigated the expression of EP3 protein in the conjunctiva of
      patients with various ocular surface diseases such as SJS/TEN, chemical eye
      burns, Mooren's ulcers, and ocular cicatricial pemphigoid (OCP).
      METHODOLOGY/PRINCIPAL FINDINGS: Conjunctival tissues were obtained from patients
      undergoing surgical reconstruction of the ocular surface due to SJS/TEN, chemical
      eye burns, and OCP, and from patients with Mooren's ulcers treated by resection
      of the inflammatory conjunctiva. The controls were nearly normal human
      conjunctival tissues acquired at surgery for conjunctivochalasis. We performed
      immunohistological analysis of the EP3 protein and evaluated the
      immunohistological staining of EP3 protein in the conjunctival epithelium of
      patients with ocular surface diseases. EP3 was expressed in the conjunctival
      epithelium of patients with chemical eye burns and Mooren's ulcer and in normal
      human conjunctival epithelium. However, it was markedly down-regulated in the
      conjunctival epithelium of SJS/TEN and OCP patients. CONCLUSIONS: We posit an
      association between the down-regulation of EP3 in conjunctival epithelium and the
      pathogenesis and pathology of SJS/TEN and OCP, and suggest a common mechanism(s)
      in the pathology of these diseases. The examination of EP3 protein expression in
      conjunctival epithelium may aid in the differential diagnosis of various ocular
      surface diseases.

PMID- 21966457
TI  - Genomic structure of and genome-wide recombination in the Saccharomyces
      cerevisiae S288C progenitor isolate EM93.
AB  - The diploid isolate EM93 is the main ancestor to the widely used Saccharomyces
      cerevisiae haploid laboratory strain, S288C. In this study, we generate a high
      resolution overview of the genetic differences between EM93 and S288C. We show
      that EM93 is heterozygous for >45,000 polymorphisms, including large sequence
      polymorphisms, such as deletions and a Saccharomyces paradoxus introgression. We
      also find that many large sequence polymorphisms (LSPs) are associated with Ty
      elements and sub-telomeric regions. We identified 2,965 genetic markers, which we
      then used to genotype 120 EM93 tetrads. In addition to deducing the structures of
      all EM93 chromosomes, we estimate that the average EM93 meiosis produces 144
      detectable recombination events, consisting of 87 crossover and 31 non-crossover
      gene conversion events. Of the 50 polymorphisms showing the highest levels of non
      crossover gene conversions, only three deviated from parity, all of which were
      near heterozygous LSPs. We find that non-telomeric heterozygous LSPs
      significantly reduce meiotic recombination in adjacent intervals, while sub
      telomeric LSPs have no discernable effect on recombination. We identified 203
      recombination hotspots, relatively few of which are hot for both non-crossover
      gene conversions and crossovers. Strikingly, we find that recombination hotspots
      show limited conservation. Some novel hotspots are found adjacent to heterozygous
      LSPs that eliminate other hotspots, suggesting that hotspots may appear and
      disappear relatively rapidly.

PMID- 21966458
TI  - Global inhibition of reactive oxygen species (ROS) inhibits paclitaxel-induced
      painful peripheral neuropathy.
AB  - Paclitaxel (Taxol(r)) is a widely used chemotherapeutic agent that has a major
      dose limiting side-effect of painful peripheral neuropathy. Currently there is no
      effective therapy for the prevention or treatment of chemotherapy-induced painful
      peripheral neuropathies. Evidence for mitochondrial dysfunction during paclitaxel
      induced pain was previously indicated with the presence of swollen and vacuolated
      neuronal mitochondria. As mitochondria are a major source of reactive oxygen
      species (ROS), the aim of this study was to examine whether pharmacological
      inhibition of ROS could reverse established paclitaxel-induced pain or prevent
      the development of paclitaxel-induced pain. Using a rat model of paclitaxel
      induced pain (intraperitoneal 2 mg/kg paclitaxel on days 0, 2, 4 & 6), the
      effects of a non-specific ROS scavenger, N-tert-Butyl-alpha-phenylnitrone (PBN)
      and a superoxide selective scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1
      oxyl (TEMPOL) were compared. Systemic 100 mg/kg PBN administration markedly
      inhibited established paclitaxel-induced mechanical hypersensitivity to von Frey
      8 g and 15 g stimulation and cold hypersensitivity to plantar acetone
      application. Daily systemic administration of 50 mg/kg PBN (days -1 to 13)
      completely prevented mechanical hypersensitivity to von Frey 4 g and 8 g
      stimulation and significantly attenuated mechanical hypersensitivity to von Frey
      15 g. Systemic 100 mg/kg TEMPOL had no effect on established paclitaxel-induced
      mechanical or cold hypersensitivity. High dose (250 mg/kg) systemic TEMPOL
      significantly inhibited mechanical hypersensitivity to von Frey 8 g & 15 g, but
      to a lesser extent than PBN. Daily systemic administration of 100 mg/kg TEMPOL
      (day -1 to 12) did not affect the development of paclitaxel-induced mechanical
      hypersensitivity. These data suggest that ROS play a causal role in the
      development and maintenance of paclitaxel-induced pain, but such effects cannot
      be attributed to superoxide radicals alone.

PMID- 21966459
TI  - Transcriptional activation of OsDERF1 in OsERF3 and OsAP2-39 negatively modulates
      ethylene synthesis and drought tolerance in rice.
AB  - The phytohormone ethylene is a key signaling molecule that regulates a variety of
      developmental processes and stress responses in plants. Transcriptional
      modulation is a pivotal process controlling ethylene synthesis, which further
      triggers the expression of stress-related genes and plant adaptation to stresses;
      however, it is unclear how this process is transcriptionally modulated in rice.
      In the present research, we report the transcriptional regulation of a novel rice
      ethylene response factor (ERF) in ethylene synthesis and drought tolerance.
      Through analysis of transcriptional data, one of the drought-responsive ERF
      genes, OsDERF1, was identified for its activation in response to drought,
      ethylene and abscisic acid. Transgenic plants overexpressing OsDERF1 (OE) led to
      reduced tolerance to drought stress in rice at seedling stage, while knockdown of
      OsDERF1 (RI) expression conferred enhanced tolerance at seedling and tillering
      stages. This regulation was supported by negative modulation in osmotic
      adjustment response. To elucidate the molecular basis of drought tolerance, we
      identified the target genes of OsDERF1 using the Affymetrix GeneChip, including
      the activation of cluster stress-related negative regulators such as ERF
      repressors. Biochemical and molecular approaches showed that OsDERF1 at least
      directly interacted with the GCC box in the promoters of ERF repressors OsERF3
      and OsAP2-39. Further investigations showed that OE seedlings had reduced
      expression (while RI lines showed enhanced expression) of ethylene synthesis
      genes, thereby resulting in changes in ethylene production. Moreover,
      overexpression of OsERF3/OsAP2-39 suppressed ethylene synthesis. In addition,
      application of ACC recovered the drought-sensitive phenotype in the lines
      overexpressing OsERF3, showing that ethylene production contributed to drought
      response in rice. Thus our data reveal that a novel ERF transcriptional cascade
      modulates drought response through controlling the ethylene synthesis, deepening
      our understanding of the regulation of ERF proteins in ethylene related drought
      response.

PMID- 21966460
TI  - Manifestation of incompleteness in obsessive-compulsive disorder (OCD) as reduced
      functionality and extended activity beyond task completion.
AB  - BACKGROUND: This study focused on hypotheses regarding the source of
      incompleteness in obsessive-compulsive disorder (OCD). For this, we had to
      document the behavioral manifestation of incompleteness in compulsive rituals,
      predicting that an exaggerated focus on acts that are appropriate for the task
      will support the hypothesis on heightened responsibility/perfectionism. In
      contrast, activity past the expected terminal act for the motor task would
      support the "stop signal deficiency" hypothesis. METHODOLOGY AND PRINCIPAL
      FINDINGS: We employed video-telemetry to analyze 39 motor OCD rituals and
      compared each with a similar task performed by a non-OCD individual, in order to
      objectively and explicitly determine the functional end of the activity. We found
      that 75% of OCD rituals comprised a "tail," which is a section that follows the
      functional end of the task that the patients ascribed to their activity. The
      other 25% tailless rituals comprised a relatively high number and higher rate of
      repetition of non-functional acts. Thus, in rituals with tail, incompleteness was
      manifested by the mere presence of the tail whereas in tailless rituals,
      incompleteness was manifested by the reduced functionality of the task due to an
      inflated execution and repetition of non-functional acts. CONCLUSIONS: The
      prevalence of activity after the functional end ("tail") and the elevated non
      functionality in OCD motor rituals support the "lack of stop signal" theories as
      the underlying mechanism in OCD. Furthermore, the presence and content of the
      tail might have a therapeutic potential in cognitive-behavior therapy.

PMID- 21966461
TI  - A monoclonal antibody to O-acetyl-GD2 ganglioside and not to GD2 shows potent
      anti-tumor activity without peripheral nervous system cross-reactivity.
AB  - BACKGROUND: Monoclonal antibodies (mAb) against GD2 ganglioside have been shown
      to be effective for the treatment of neuroblastoma. Beneficial actions are,
      however, associated with generalized pain due to the binding of anti- GD2 mAbs to
      peripheral nerve fibers followed by complement activation. Neuroblastoma cells
      that express GD2 also express its O-acetyl derivative, O-acetyl- GD2 ganglioside
      (OAcGD2). Hence, we investigated the distribution of OAcGD2 in human tissues
      using mAb 8B6 to study the cross-reactivity of mAb 8B6 with human tissues.
      METHODOLOGY/PRINCIPAL FINDINGS: The distribution of OAcGD2 was performed in
      normal and malignant tissues using an immunoperoxydase technique. Anti-tumor
      properties of mAb 8B6 were studied in vitro and in vivo in a transplanted tumor
      model in mice. We found that OAcGD2 is not expressed by peripheral nerve fibers.
      Furthermore, we demonstrated that mAb 8B6 was very effective in the in vitro and
      in vivo suppression of the growth of tumor cells. Importantly, mAb 8B6 anti-tumor
      efficacy was comparable to that of mAb 14G2a specific to GD2.
      CONCLUSION/SIGNIFICANCE: Development of therapeutic antibodies specific to OAcGD2
      may offer treatment options with reduced adverse side effects, thereby allowing
      dose escalation of antibodies.

PMID- 21966462
TI  - Exploring the fundamental dynamics of error-based motor learning using a
      stationary predictive-saccade task.
AB  - The maintenance of movement accuracy uses prior performance errors to correct
      future motor plans; this motor-learning process ensures that movements remain
      quick and accurate. The control of predictive saccades, in which anticipatory
      movements are made to future targets before visual stimulus information becomes
      available, serves as an ideal paradigm to analyze how the motor system utilizes
      prior errors to drive movements to a desired goal. Predictive saccades constitute
      a stationary process (the mean and to a rough approximation the variability of
      the data do not vary over time, unlike a typical motor adaptation paradigm). This
      enables us to study inter-trial correlations, both on a trial-by-trial basis and
      across long blocks of trials. Saccade errors are found to be corrected on a trial
      by-trial basis in a direction-specific manner (the next saccade made in the same
      direction will reflect a correction for errors made on the current saccade).
      Additionally, there is evidence for a second, modulating process that exhibits
      long memory. That is, performance information, as measured via inter-trial
      correlations, is strongly retained across a large number of saccades (about 100
      trials). Together, this evidence indicates that the dynamics of motor learning
      exhibit complexities that must be carefully considered, as they cannot be fully
      described with current state-space (ARMA) modeling efforts.

PMID- 21966463
TI  - A genetic polymorphism (rs17251221) in the calcium-sensing receptor gene (CASR)
      is associated with stone multiplicity in calcium nephrolithiasis.
AB  - Calcium nephrolithiasis is one of the most common causes of renal stones. While
      the prevalence of this disease has increased steadily over the last 3 decades,
      its pathogenesis is still unclear. Previous studies have indicated that a genetic
      polymorphism (rs17251221) in the calcium-sensing receptor gene (CASR) is
      associated with the total serum calcium levels. In this study, we collected DNA
      samples from 480 Taiwanese subjects (189 calcium nephrolithiasis patients and 291
      controls) for genotyping the CASR gene. Our results indicated no significant
      association between the CASR polymorphism (rs17251221) and the susceptibility of
      calcium nephrolithiasis. However, we found a significant association between
      rs17251221 and stone multiplicity. The risk of stone multiplicity was higher in
      patients with the GG+GA genotype than in those with the AA genotype (chi-square
      test: P = 0.008; odds ratio  =  4.79; 95% confidence interval, 1.44-15.92; Yates'
      correction for chi-square test: P = 0.013). In conclusion, our results provide
      evidence supporting the genetic effects of CASR on the pathogenesis of calcium
      nephrolithiasis.

PMID- 21966464
TI  - Identification of probable early-onset biomarkers for tuberculosis disease
      progression.
AB  - Determining what constitutes protective immunity to TB is critical for the
      development of improved diagnostics and vaccines. The comparison of the immune
      system between contacts of TB patients, who later develop TB disease
      (progressors), versus contacts who remain healthy (non-progressors), allows for
      identification of predictive markers of TB disease. This study provides the first
      comprehensive analysis of the immune system of progressors and non-progressors
      using a well-characterised TB case-contact (TBCC) platform in The Gambia, West
      Africa. 22 progressors and 31 non-progressors were analysed at recruitment, 3
      months and 18 months (time to progression: median[IQR] of 507[187-714] days).
      Immunophenotyping of PBMC, plasma cytokine levels and RT-MLPA analysis of whole
      blood-derived RNA was performed to capture key immune system parameters. At
      recruitment, progressors had lower PBMC proportions of CD4+ T cells, NKT cells
      and B cells relative to non-progressors. Analysis of the plasma showed higher
      levels of IL-18 in progressors compared to non-progressors and analysis of the
      RNA showed significantly lower gene expression of Bcl2 but higher CCR7 in
      progressors compared to non-progressors. This study shows several markers that
      may predict the onset of active TB at a very early stage after infection. Once
      these markers have been validated in larger studies, they provide avenues to
      prospectively identify people at risk of developing TB, a key issue in the
      testing of new TB vaccines.

PMID- 21966465
TI  - Deficient of a clock gene, brain and muscle Arnt-like protein-1 (BMAL1), induces
      dyslipidemia and ectopic fat formation.
AB  - A link between circadian rhythm and metabolism has long been discussed. Circadian
      rhythm is controlled by positive and negative transcriptional and translational
      feedback loops composed of several clock genes. Among clock genes, the brain and
      muscle Arnt-like protein-1 (BMAL1) and circadian locomotor output cycles kaput
      (CLOCK) play important roles in the regulation of the positive rhythmic
      transcription. In addition to control of circadian rhythm, we have previously
      shown that BMAL1 regulates adipogenesis. In metabolic syndrome patients, the
      function of BMAL1 is dysregulated in visceral adipose tissue. In addition,
      analysis of SNPs has revealed that BMAL1 is associated with susceptibility to
      hypertension and type II diabetes. Furthermore, the significant roles of BMAL1 in
      pancreatic beta cells proliferation and maturation were recently reported. These
      results suggest that BMAL1 regulates energy homeostasis. Therefore, in this
      study, we examined whether loss of BMAL1 function is capable of inducing
      metabolic syndrome. Deficient of the Bmal1 gene in mice resulted in elevation of
      the respiratory quotient value, indicating that BMAL1 is involved in the
      utilization of fat as an energy source. Indeed, lack of Bmal1 reduced the
      capacity of fat storage in adipose tissue, resulting in an increase in the levels
      of circulating fatty acids, including triglycerides, free fatty acids, and
      cholesterol. Elevation of the circulating fatty acids level induced the formation
      of ectopic fat in the liver and skeletal muscle in Bmal1 -/- mice. Interestingly,
      ectopic fat formation was not observed in tissue-specific (liver or skeletal
      muscle) Bmal1 -/- mice even under high fat diet feeding condition. Therefore, we
      were led to conclude that BMAL1 is a crucial factor in the regulation of energy
      homeostasis, and disorders of the functions of BMAL1 lead to the development of
      metabolic syndrome.

PMID- 21966466
TI  - HIV protease inhibitors act as competitive inhibitors of the cytoplasmic glucose
      binding site of GLUTs with differing affinities for GLUT1 and GLUT4.
AB  - The clinical use of several first generation HIV protease inhibitors (PIs) is
      associated with the development of insulin resistance. Indinavir has been shown
      to act as a potent reversible noncompetitive inhibitor of zero-trans glucose
      influx via direct interaction with the insulin responsive facilitative glucose
      transporter GLUT4. Newer drugs within this class have differing effects on
      insulin sensitivity in treated patients. GLUTs are known to contain two distinct
      glucose-binding sites that are located on opposite sides of the lipid bilayer. To
      determine whether interference with the cytoplasmic glucose binding site is
      responsible for differential effects of PIs on glucose transport, intact
      intracellular membrane vesicles containing GLUT1 and GLUT4, which have an
      inverted transporter orientation relative to the plasma membrane, were isolated
      from 3T3-L1 adipocytes. The binding of biotinylated ATB-BMPA, a membrane
      impermeable bis-mannose containing photolabel, was determined in the presence of
      indinavir, ritonavir, atazanavir, tipranavir, and cytochalasin b. Zero-trans 2
      deoxyglucose transport was measured in both 3T3-L1 fibroblasts and primary rat
      adipocytes acutely exposed to these compounds. PI inhibition of glucose transport
      correlated strongly with the PI inhibition of ATB-BMPA/transporter binding. At
      therapeutically relevant concentrations, ritonavir was not selective for GLUT4
      over GLUT1. Indinavir was found to act as a competitive inhibitor of the
      cytoplasmic glucose binding site of GLUT4 with a K(I) of 8.2 uM. These data
      establish biotinylated ATB-BMPA as an effective probe to quantify accessibility
      of the endofacial glucose-binding site in GLUTs and reveal that the ability of
      PIs to block this site differs among drugs within this class. This provides
      mechanistic insight into the basis for the clinical variation in drug-related
      metabolic toxicity.

PMID- 21966467
TI  - Increased MDSC accumulation and Th2 biased response to influenza A virus
      infection in the absence of TLR7 in mice.
AB  - Toll-like receptors (TLRs) play an important role in the induction of innate and
      adaptive immune response against influenza A virus (IAV) infection; however, the
      role of Toll-like receptor 7 (TLR7) during the innate immune response to IAV
      infection and the cell types affected by the absence of TLR7 are not clearly
      understood. In this study, we show that myeloid derived suppressor cells (MDSC)
      accumulate in the lungs of TLR7 deficient mice more so than in wild-type C57Bl/6
      mice, and display increased cytokine expression. Furthermore, there is an
      increase in production of Th2 cytokines by TLR7(-/-) compared with wildtype CD4+
      T-cells in vivo, leading to a Th2 polarized humoral response. Our findings
      indicate that TLR7 modulates the accumulation of MDSCs during an IAV infection in
      mice, and that lack of TLR7 signaling leads to a Th2-biased response.

PMID- 21966468
TI  - A toll-like receptor 2 pathway regulates the Ppargc1a/b metabolic co-activators
      in mice with Staphylococcal aureus sepsis.
AB  - Activation of the host antibacterial defenses by the toll-like receptors (TLR)
      also selectively activates energy-sensing and metabolic pathways, but the
      mechanisms are poorly understood. This includes the metabolic and mitochondrial
      biogenesis master co-activators, Ppargc1a (PGC-1alpha) and Ppargc1b (PGC-1beta)
      in Staphylococcus aureus (S. aureus) sepsis. The expression of these genes in the
      liver is markedly attenuated inTLR2(-/-) mice and markedly accentuated in TLR4(-/
      ) mice compared with wild type (WT) mice. We sought to explain this difference by
      using specific TLR-pathway knockout mice to test the hypothesis that these co
      activator genes are directly regulated through TLR2 signaling. By comparing their
      responses to S. aureus with WT mice, we found that MyD88-deficient and MAL
      deficient mice expressed hepatic Ppargc1a and Ppargc1b normally, but that neither
      gene was activated in TRAM-deficient mice. Ppargc1a/b activation did not require
      NF-kbeta, but did require an interferon response factor (IRF), because neither
      gene was activated in IRF-3/7 double-knockout mice in sepsis, but both were
      activated normally in Unc93b1-deficient (3d) mice. Nuclear IRF-7 levels in TLR2(
      /-) and TLR4(-/-) mice decreased and increased respectively post-inoculation and
      IRF-7 DNA-binding at the Ppargc1a promoter was demonstrated by chromatin
      immunoprecipitation. Also, a TLR2-TLR4-TRAM native hepatic protein complex was
      detected by immunoprecipitation within 6 h of S. aureus inoculation that could
      support MyD88-independent signaling to Ppargc1a/b. Overall, these findings
      disclose a novel MyD88-independent pathway in S. aureus sepsis that links TLR2
      and TLR4 signaling in innate immunity to Ppargc1a/b gene regulation in a critical
      metabolic organ, the liver, by means of TRAM, TRIF, and IRF-7.

PMID- 21966469
TI  - Early markers of glycaemic control in children with type 1 diabetes mellitus.
AB  - BACKGROUND: Type 1 diabetes mellitus (T1DM) may lead to severe long-term health
      consequences. In a longitudinal study, we aimed to identify factors present at
      diagnosis and 6 months later that were associated with glycosylated haemoglobin
      (HbA(1c)) levels at 24 months after T1DM diagnosis, so that diabetic children at
      risk of poor glycaemic control may be identified. METHODS: 229 children <15 years
      of age diagnosed with T1DM in the Auckland region were studied. Data collected at
      diagnosis were: age, sex, weight, height, ethnicity, family living arrangement,
      socio-economic status (SES), T1DM antibody titre, venous pH and bicarbonate. At 6
      and 24 months after diagnosis we collected data on weight, height, HbA(1c) level,
      and insulin dose. RESULTS: Factors at diagnosis that were associated with higher
      HbA(1c) levels at 6 months: female sex (p<0.05), lower SES (p<0.01), non-European
      ethnicity (p<0.01) and younger age (p<0.05). At 24 months, higher HbA(1c) was
      associated with lower SES (p<0.001), Pacific Island ethnicity (p<0.001), not
      living with both biological parents (p<0.05), and greater BMI SDS (p<0.05). A
      regression equation to predict HbA(1c) at 24 months was consequently developed.
      CONCLUSIONS: Deterioration in glycaemic control shortly after diagnosis in
      diabetic children is particularly marked in Pacific Island children and in those
      not living with both biological parents. Clinicians need to be aware of factors
      associated with poor glycaemic control beyond the remission phase, so that more
      effective measures can be implemented shortly after diagnosis to prevent
      deterioration in diabetes control.

PMID- 21966470
TI  - Isogenic pairs of wild type and mutant induced pluripotent stem cell (iPSC) lines
      from Rett syndrome patients as in vitro disease model.
AB  - Rett syndrome (RTT) is an autism spectrum developmental disorder caused by
      mutations in the X-linked methyl-CpG binding protein 2 (MECP2) gene. Excellent
      RTT mouse models have been created to study the disease mechanisms, leading to
      many important findings with potential therapeutic implications. These include
      the identification of many MeCP2 target genes, better understanding of the
      neurobiological consequences of the loss- or mis-function of MeCP2, and drug
      testing in RTT mice and clinical trials in human RTT patients. However, because
      of potential differences in the underlying biology between humans and common
      research animals, there is a need to establish cell culture-based human models
      for studying disease mechanisms to validate and expand the knowledge acquired in
      animal models. Taking advantage of the nonrandom pattern of X chromosome
      inactivation in female induced pluripotent stem cells (iPSC), we have generated
      isogenic pairs of wild type and mutant iPSC lines from several female RTT
      patients with common and rare RTT mutations. R294X (arginine 294 to stop codon)
      is a common mutation carried by 5-6% of RTT patients. iPSCs carrying the R294X
      mutation has not been studied. We differentiated three R294X iPSC lines and their
      isogenic wild type control iPSC into neurons with high efficiency and
      consistency, and observed characteristic RTT pathology in R294X neurons. These
      isogenic iPSC lines provide unique resources to the RTT research community for
      studying disease pathology, screening for novel drugs, and testing toxicology.

PMID- 21966471
TI  - Antibodies to henipavirus or henipa-like viruses in domestic pigs in Ghana, West
      Africa.
AB  - Henipaviruses, Hendra virus (HeV) and Nipah virus (NiV), have Pteropid bats as
      their known natural reservoirs. Antibodies against henipaviruses have been found
      in Eidolon helvum, an old world fruit bat species, and henipavirus-like nucleic
      acid has been detected in faecal samples from E. helvum in Ghana. The initial
      outbreak of NiV in Malaysia led to over 265 human encephalitis cases, including
      105 deaths, with infected pigs acting as amplifier hosts for NiV during the
      outbreak. We detected non-neutralizing antibodies against viruses of the genus
      Henipavirus in approximately 5% of pig sera (N = 97) tested in Ghana, but not in
      a small sample of other domestic species sampled under a E. helvum roost.
      Although we did not detect neutralizing antibody, our results suggest prior
      exposure of the Ghana pig population to henipavirus(es). Because a wide diversity
      of henipavirus-like nucleic acid sequences have been found in Ghanaian E. helvum,
      we hypothesise that these pigs might have been infected by henipavirus(es)
      sufficiently divergent enough from HeVor NiV to produce cross-reactive, but not
      cross-neutralizing antibodies to HeV or NiV.

PMID- 21966472
TI  - Yeast methylotrophy and autophagy in a methanol-oscillating environment on
      growing Arabidopsis thaliana leaves.
AB  - The yeast Candida boidinii capable of growth on methanol proliferates and
      survives on the leaves of Arabidopsis thaliana. The local methanol concentration
      at the phyllosphere of growing A. thaliana exhibited daily periodicity, and yeast
      cells responded by altering both the expression of methanol-inducible genes and
      peroxisome proliferation. Even under these dynamically changing environmental
      conditions, yeast cells proliferated 3 to 4 times in 11 days. Among the C1
      metabolic enzymes, enzymes in the methanol assimilation pathway, but not
      formaldehyde dissimilation or anti-oxidizing enzymes, were necessary for yeast
      proliferation at the phyllosphere. Furthermore, both peroxisome assembly and
      pexophagy, a selective autophagy pathway that degrades peroxisomes, were
      necessary for phyllospheric proliferation. Thus, the present study sheds light on
      the life cycle and physiology of yeast in the natural environment at both the
      molecular and cellular levels.

PMID- 21966473
TI  - Analysis of 16S rRNA amplicon sequencing options on the Roche/454 next-generation
      titanium sequencing platform.
AB  - BACKGROUND: 16S rRNA gene pyrosequencing approach has revolutionized studies in
      microbial ecology. While primer selection and short read length can affect the
      resulting microbial community profile, little is known about the influence of
      pyrosequencing methods on the sequencing throughput and the outcome of microbial
      community analyses. The aim of this study is to compare differences in output,
      ease, and cost among three different amplicon pyrosequencing methods for the
      Roche/454 Titanium platform METHODOLOGY/PRINCIPAL FINDINGS: The following three
      pyrosequencing methods for 16S rRNA genes were selected in this study: Method-1
      (standard method) is the recommended method for bi-directional sequencing using
      the LIB-A kit; Method-2 is a new option designed in this study for unidirectional
      sequencing with the LIB-A kit; and Method-3 uses the LIB-L kit for unidirectional
      sequencing. In our comparison among these three methods using 10 different
      environmental samples, Method-2 and Method-3 produced 1.5-1.6 times more useable
      reads than the standard method (Method-1), after quality-based trimming, and did
      not compromise the outcome of microbial community analyses. Specifically, Method
      3 is the most cost-effective unidirectional amplicon sequencing method as it
      provided the most reads and required the least effort in consumables management.
      CONCLUSIONS: Our findings clearly demonstrated that alternative pyrosequencing
      methods for 16S rRNA genes could drastically affect sequencing output (e.g.
      number of reads before and after trimming) but have little effect on the outcomes
      of microbial community analysis. This finding is important for both researchers
      and sequencing facilities utilizing 16S rRNA gene pyrosequencing for microbial
      ecological studies.

PMID- 21966474
TI  - Stochastic ontogenetic allometry: the statistical dynamics of relative growth.
AB  - BACKGROUND: In the absence of stochasticity, allometric growth throughout
      ontogeny is axiomatically described by the logarithm-transformed power-law model,
      thetat = log(a) b + kphi(t), where thetat = theta(t) and phit = phi(t) are the
      logarithmic sizes of two traits at any given time t. Realistically, however,
      stochasticity is an inherent property of ontogenetic allometry. Due to the
      inherent stochasticity in both thetat and phit, the ontogenetic allometry
      coefficients, log(a) b and k, can vary with t and have intricate temporal
      distributions that are governed by the central and mixed moments of the random
      ontogenetic growth functions, thetat and phit. Unfortunately, there is no
      probabilistic model for analyzing these informative ontogenetic statistical
      moments. METHODOLOGY/PRINCIPAL FINDINGS: This study treats thetat and phit as
      correlated stochastic processes to formulate the exact probabilistic version of
      each of the ontogenetic allometry coefficients. In particular, the statistical
      dynamics of relative growth is addressed by analyzing the allometric growth
      factors that affect the temporal distribution of the probabilistic version of the
      relative growth rate, k = Dt(u<Omegat>)/Dt(v<Omegat>), where <Omegat> is the
      expected value of the ratio of stochastic thetat to stochastic phit, and
      u<Omegat> and v<Omegat> are the numerator and the denominator of <Omegat>,
      respectively. These allometric growth factors, which provide important insight
      into ontogenetic allometry but appear only when stochasticity is introduced,
      describe the central and mixed moments of thetat and phit as differentiable real
      valued functions of t. CONCLUSIONS/SIGNIFICANCE: Failure to account for the
      inherent stochasticity in both thetat and phit leads not only to the
      miscalculation of k, but also to the omission of all of the informative
      ontogenetic statistical moments that affect the size of traits and the timing and
      rate of development of traits. Furthermore, even though the stochastic process
      thetat and the stochastic process phit are linearly related, k can vary with t.

PMID- 21966475
TI  - Role of chaperone mediated autophagy (CMA) in the degradation of misfolded N-CoR
      protein in non-small cell lung cancer (NSCLC) cells.
AB  - Nuclear receptor co-repressor (N-CoR) plays important role in transcriptional
      control mediated by several tumor suppressor proteins. Recently, we reported a
      role of misfolded-conformation dependent loss (MCDL) of N-CoR in the activation
      of oncogenic survival pathway in acute promyelocytic leukemia (APL). Since N-CoR
      plays important role in cellular homeostasis in various tissues, therefore, we
      hypothesized that an APL like MCDL of N-CoR might also be involved in other
      malignancy. Indeed, our initial screening of N-CoR status in various leukemia and
      solid tumor cells revealed an APL like MCDL of N-CoR in primary and secondary
      tumor cells derived from non-small cell lung cancer (NSCLC). The NSCLC cell
      specific N-CoR loss could be blocked by Kaletra, a clinical grade protease
      inhibitor and by genistein, an inhibitor of N-CoR misfolding previously
      characterized by us. The misfolded N-CoR presented in NSCLC cells was linked to
      the amplification of ER stress and was subjected to degradation by NSCLC cell
      specific aberrant protease activity. In NSCLC cells, misfolded N-CoR was found to
      be associated with Hsc70, a molecular chaperone involved in chaperone mediated
      autophagy (CMA). Genetic and chemical inhibition of Lamp2A, a rate limiting
      factor of CMA, significantly blocked the loss of N-CoR in NSCLC cells, suggesting
      a crucial role of CMA in N-CoR degradation. These findings identify an important
      role of CMA-induced degradation of misfolded N-CoR in the neutralization of ER
      stress and suggest a possible role of misfolded N-CoR protein in the activation
      of oncogenic survival pathway in NSCLC cells.

PMID- 21966476
TI  - GW501516, a PPARdelta agonist, ameliorates tubulointerstitial inflammation in
      proteinuric kidney disease via inhibition of TAK1-NFkappaB pathway in mice.
AB  - Peroxisome proliferator-activated receptors (PPARs) are a nuclear receptor family
      of ligand-inducible transcription factors, which have three different isoforms:
      PPARalpha, delta and gamma. It has been demonstrated that PPARalpha and gamma
      agonists have renoprotective effects in proteinuric kidney diseases; however, the
      role of PPARdelta agonists in kidney diseases remains unclear. Thus, we examined
      the renoprotective effect of GW501516, a PPARdelta agonist, in a protein-overload
      mouse nephropathy model and identified its molecular mechanism. Mice fed with a
      control diet or GW501516-containing diet were intraperitoneally injected with
      free fatty acid (FFA)-bound albumin or PBS(-). In the control group, protein
      overload caused tubular damages, macrophage infiltration and increased mRNA
      expression of MCP-1 and TNFalpha. These effects were prevented by GW501516
      treatment. In proteinuric kidney diseases, excess exposure of proximal tubular
      cells to albumin, FFA bound to albumin or cytokines such as TNFalpha is
      detrimental. In vitro studies using cultured proximal tubular cells showed that
      GW501516 attenuated both TNFalpha- and FFA (palmitate)-induced, but not albumin
      induced, MCP-1 expression via direct inhibition of the TGF-beta activated kinase
      1 (TAK1)-NFkappaB pathway, a common downstream signaling pathway to TNFalpha
      receptor and toll-like receptor-4. In conclusion, we demonstrate that GW501516
      has an anti-inflammatory effect in renal tubular cells and may serve as a
      therapeutic candidate to attenuate tubulointerstitial lesions in proteinuric
      kidney diseases.

PMID- 21966477
TI  - CYP5122A1, a novel cytochrome P450 is essential for survival of Leishmania
      donovani.
AB  - BACKGROUND: Cytochrome P450s (CYP450s) are hemoproteins catalysing diverse
      biochemical reactions important for metabolism of xenobiotics and synthesis of
      physiologically important compounds such as sterols. Therefore, they are
      functionally important for survival of invading pathogens. One such opportunistic
      pathogen Leishmania donovani causes visceral leishmaniasis worldwide, which is an
      important public health problem due to significant disease burden. The parasite
      genome database, Gene DB, annotates 3 CYP450s in Leishmania, however, the
      functional role of cytochrome P450 enzymes in Leishmania spp. remains elusive.
      METHODOLOGY/PRINCIPAL FINDINGS: A CYP450-like gene cloned from Leishmania
      donovani was identified as a novel CYP450, the CYP5122A1. Upon co-localization
      with organelle specific markers, CYP5122A1 distribution was shown to be localized
      in the promastigote ER, mitochondria and the glycosomes. Replacement of one
      allele of CYP5122A1 with either neomycin or hygromycin gene by homologous
      recombination in Leishmania promastigotes induced substantial reduction of
      CYP5122A1 expression. These parasites showed impaired growth, lower mitochondrial
      Ca(2+) and membrane potential resulting in low ATP generation. Also, these
      parasites were less infective in vitro and in vivo than their wild-type
      counterparts as assessed by incubation of Leishmania promastigotes with
      macrophages in vitro as well as through administration of parasites into
      hamsters. The HKOs were more susceptible to drugs like miltefosine and antimony,
      but showed reduced sensitivity to amphotericin B. Removal of two alleles of
      CYP5122A1 did not allow the parasites to survive. The mutant parasites showed 3.5
      times lower ergosterol level as compared to the wild-type parasites when
      estimated by Gas chromatography/mass spectrometry. Complementation of CYP5122A1
      through episomal expression of protein by using pXG-GFP+2 vector partially
      rescued CYP5122A1 expression and restored ergosterol levels by 1.8 times.
      Phenotype reversal included restored growth pattern and lesser drug
      susceptibility. CONCLUSIONS/SIGNIFICANCE: In summary, this study establishes
      CYP5122A1 as an important molecule linked to processes like cell growth,
      infection and ergosterol biosynthesis in Leishmania donovani.

PMID- 21966478
TI  - Short-term visual deprivation does not enhance passive tactile spatial acuity.
AB  - An important unresolved question in sensory neuroscience is whether, and if so
      with what time course, tactile perception is enhanced by visual deprivation. In
      three experiments involving 158 normally sighted human participants, we assessed
      whether tactile spatial acuity improves with short-term visual deprivation over
      periods ranging from under 10 to over 110 minutes. We used an automated,
      precisely controlled two-interval forced-choice grating orientation task to
      assess each participant's ability to discern the orientation of square-wave
      gratings pressed against the stationary index finger pad of the dominant hand. A
      two-down one-up staircase (Experiment 1) or a Bayesian adaptive procedure
      (Experiments 2 and 3) was used to determine the groove width of the grating whose
      orientation each participant could reliably discriminate. The experiments
      consistently showed that tactile grating orientation discrimination does not
      improve with short-term visual deprivation. In fact, we found that tactile
      performance degraded slightly but significantly upon a brief period of visual
      deprivation (Experiment 1) and did not improve over periods of up to 110 minutes
      of deprivation (Experiments 2 and 3). The results additionally showed that
      grating orientation discrimination tends to improve upon repeated testing, and
      confirmed that women significantly outperform men on the grating orientation
      task. We conclude that, contrary to two recent reports but consistent with an
      earlier literature, passive tactile spatial acuity is not enhanced by short-term
      visual deprivation. Our findings have important theoretical and practical
      implications. On the theoretical side, the findings set limits on the time course
      over which neural mechanisms such as crossmodal plasticity may operate to drive
      sensory changes; on the practical side, the findings suggest that researchers who
      compare tactile acuity of blind and sighted participants should not blindfold the
      sighted participants.

PMID- 21966479
TI  - Temporal and spatial evolution of brain network topology during the first two
      years of life.
AB  - The mature brain features high wiring efficiency for information transfer.
      However, the emerging process of such an efficient topology remains elusive. With
      resting state functional MRI and a large cohort of normal pediatric subjects (n =
      147) imaged during a critical time period of brain development, 3 wk- to 2 yr
      old, the temporal and spatial evolution of brain network topology is revealed.
      The brain possesses the small world topology immediately after birth, followed by
      a remarkable improvement in whole brain wiring efficiency in 1 yr olds and
      becomes more stable in 2 yr olds. Regional developments of brain wiring
      efficiency and the evolution of functional hubs suggest differential development
      trend for primary and higher order cognitive functions during the first two years
      of life. Simulations of random errors and targeted attacks reveal an age
      dependent improvement of resilience. The lower resilience to targeted attack
      observed in 3 wk old group is likely due to the fact that there are fewer well
      established long-distance functional connections at this age whose elimination
      might have more profound implications in the overall efficiency of information
      transfer. Overall, our results offer new insights into the temporal and spatial
      evolution of brain topology during early brain development.

PMID- 21966480
TI  - Towards protein crystallization as a process step in downstream processing of
      therapeutic antibodies: screening and optimization at microbatch scale.
AB  - Crystallization conditions of an intact monoclonal IgG4 (immunoglobulin G,
      subclass 4) antibody were established in vapor diffusion mode by sparse matrix
      screening and subsequent optimization. The procedure was transferred to
      microbatch conditions and a phase diagram was built showing surprisingly low
      solubility of the antibody at equilibrium. With up-scaling to process scale in
      mind, purification efficiency of the crystallization step was investigated. Added
      model protein contaminants were excluded from the crystals to more than 95%. No
      measurable loss of Fc-binding activity was observed in the crystallized and
      redissolved antibody. Conditions could be adapted to crystallize the antibody
      directly from concentrated and diafiltrated cell culture supernatant, showing
      purification efficiency similar to that of Protein A chromatography. We conclude
      that crystallization has the potential to be included in downstream processing as
      a low-cost purification or formulation step.

PMID- 21966481
TI  - Multisensory information facilitates reaction speed by enlarging activity
      difference between superior colliculus hemispheres in rats.
AB  - Animals can make faster behavioral responses to multisensory stimuli than to
      unisensory stimuli. The superior colliculus (SC), which receives multiple inputs
      from different sensory modalities, is considered to be involved in the initiation
      of motor responses. However, the mechanism by which multisensory information
      facilitates motor responses is not yet understood. Here, we demonstrate that
      multisensory information modulates competition among SC neurons to elicit faster
      responses. We conducted multiunit recordings from the SC of rats performing a two
      alternative spatial discrimination task using auditory and/or visual stimuli. We
      found that a large population of SC neurons showed direction-selective activity
      before the onset of movement in response to the stimuli irrespective of
      stimulation modality. Trial-by-trial correlation analysis showed that the
      premovement activity of many SC neurons increased with faster reaction speed for
      the contraversive movement, whereas the premovement activity of another
      population of neurons decreased with faster reaction speed for the ipsiversive
      movement. When visual and auditory stimuli were presented simultaneously, the
      premovement activity of a population of neurons for the contraversive movement
      was enhanced, whereas the premovement activity of another population of neurons
      for the ipsiversive movement was depressed. Unilateral inactivation of SC using
      muscimol prolonged reaction times of contraversive movements, but it shortened
      those of ipsiversive movements. These findings suggest that the difference in
      activity between the SC hemispheres regulates the reaction speed of motor
      responses, and multisensory information enlarges the activity difference
      resulting in faster responses.

PMID- 21966482
TI  - Environmental enrichment modulates cortico-cortical interactions in the mouse.
AB  - Environmental enrichment (EE) is an experimental protocol based on a complex
      sensorimotor stimulation that dramatically affects brain development. While it is
      widely believed that the effects of EE result from the unique combination of
      different sensory and motor stimuli, it is not known whether and how cortico
      cortical interactions are shaped by EE. Since the primary visual cortex (V1) is
      one of the best characterized targets of EE, we looked for direct cortico
      cortical projections impinging on V1, and we identified a direct monosynaptic
      connection between motor cortex and V1 in the mouse brain. To measure the
      interactions between these areas under standard and EE rearing conditions, we
      used simultaneous recordings of local field potentials (LFPs) in awake, freely
      moving animals. LFP signals were analyzed by using different methods of linear
      and nonlinear analysis of time series (cross-correlation, mutual information,
      phase synchronization). We found that EE decreases the level of coupling between
      the electrical activities of the two cortical regions with respect to the control
      group. From a functional point of view, our results indicate, for the first time,
      that an enhanced sensorimotor experience impacts on the brain by affecting the
      functional crosstalk between different cortical areas.

PMID- 21966483
TI  - Phylodynamics of HIV-1 subtype B among the men-having-sex-with-men (MSM)
      population in Hong Kong.
AB  - The men-having-sex-with-men (MSM) population has become one of the major risk
      groups for HIV-1 infection in the Asia Pacific countries. Hong Kong is located in
      the centre of Asia and the transmission history of HIV-1 subtype B transmission
      among MSM remained unclear. The aim of this study was to investigate the
      transmission dynamics of HIV-1 subtype B virus in the Hong Kong MSM population.
      Samples of 125 HIV-1 subtype B infected MSM patients were recruited in this
      study. Through this study, the subtype B epidemic in the Hong Kong MSM population
      was identified spreading mainly among local Chinese who caught infection locally.
      On the other hand, HIV-1 subtype B infected Caucasian MSM caught infection mainly
      outside Hong Kong. The Bayesian phylogenetic analysis also indicated that 3
      separate subtype B epidemics with divergence dates in the 1990s had occurred. The
      first and latest epidemics were comparatively small-scaled; spreading among the
      local Chinese MSM while sauna-visiting was found to be the major sex partner
      sourcing reservoir for the first subtype B epidemic. However, the second epidemic
      was spread in a large-scale among local Chinese MSM with a number of them having
      sourced their sex partners through the internet. The epidemic virus was estimated
      to have a divergence date in 1987 and the infected population in Hong Kong had a
      logistic growth throughout the past 20 years. Our study elucidated the
      evolutionary and demographic history of HIV-1 subtype B virus in Hong Kong MSM
      population. The understanding of transmission and growth model of the subtype B
      epidemic provides more information on the HIV-1 transmission among MSM population
      in other Asia Pacific high-income countries.

PMID- 21966484
TI  - Leukemia inhibitory factor enhances endometrial stromal cell decidualization in
      humans and mice.
AB  - Adequate differentiation or decidualization of endometrial stromal cells (ESC) is
      critical for successful pregnancy in humans and rodents. Here, we investigated
      the role of leukemia inhibitory factor (LIF) in human and murine decidualization.
      Ex vivo human (H) ESC decidualization was induced by estrogen (E, 10(-8) M) plus
      medroxyprogesterone acetate (MPA, 10(-7) M). Exogenous LIF (>=50 ng/ml) induced
      STAT3 phosphorylation in non-decidualized and decidualized HESC and enhanced
      E+MPA-induced decidualization (measured by PRL secretion, P<0.05). LIF mRNA in
      HESC was down-regulated by decidualization treatment (E+MPA) whereas LIF receptor
      (R) mRNA was up-regulated, suggesting that the decidualization stimulus 'primed'
      HESC for LIF action, but that factors not present in our in vitro model were
      required to induce LIF expression. Ex vivo first trimester decidual biopsies
      secreted >100 pg/mg G-CSF, IL6, IL8, and MCP1. Decidualized HESC secreted IL6,
      IL8, IL15 and MCP1. LIF (50 ng/ml) up-regulated IL6 and IL15 (P<0.05) secretion
      in decidualized HESC compared to 0.5 ng/ml LIF. In murine endometrium, LIF and
      LIFR immunolocalized to decidualized stromal cells on day 5 of gestation (day 0 =
      day of plug detection). Western blotting confirmed that LIF and the LIFR were up
      regulated in intra-implantation sites compared to inter-implantation sites on Day
      5 of gestation. To determine the role of LIF during in vivo murine
      decidualization, intra-peritoneal injections of a long-acting LIF antagonist
      (PEGLA; 900 or 1200 ug) were given just post-attachment, during the initiation of
      decidualization on day 4. PEGLA treatment reduced implantation site decidual area
      (P<0.05) and desmin staining immuno-intensity (P<0.05) compared to control on day
      6 of gestation. This study demonstrated that LIF was an important regulator of
      decidualization in humans and mice and data provides insight into the processes
      underlying decidualization, which are important for understanding implantation
      and placentation.

PMID- 21966485
TI  - Metabolic adaptation in transplastomic plants massively accumulating recombinant
      proteins.
AB  - BACKGROUND: Recombinant chloroplasts are endowed with an astonishing capacity to
      accumulate foreign proteins. However, knowledge about the impact on resident
      proteins of such high levels of recombinant protein accumulation is lacking.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we used proteomics to characterize tobacco
      (Nicotiana tabacum) plastid transformants massively accumulating a p
      hydroxyphenyl pyruvate dioxygenase (HPPD) or a green fluorescent protein (GFP).
      While under the conditions used no obvious modifications in plant phenotype could
      be observed, these proteins accumulated to even higher levels than ribulose 1,5
      bisphosphate carboxylase/oxygenase (Rubisco), the most abundant protein on the
      planet. This accumulation occurred at the expense of a limited number of leaf
      proteins including Rubisco. In particular, enzymes involved in CO(2) metabolism
      such as nuclear-encoded plastidial Calvin cycle enzymes and mitochondrial glycine
      decarboxylase were found to adjust their accumulation level to these novel
      physiological conditions. CONCLUSIONS/SIGNIFICANCE: The results document how
      protein synthetic capacity is limited in plant cells. They may provide new
      avenues to evaluate possible bottlenecks in recombinant protein technology and to
      maintain plant fitness in future studies aiming at producing recombinant proteins
      of interest through chloroplast transformation.

PMID- 21966486
TI  - A test of the coordinated expression hypothesis for the origin and maintenance of
      the GAL cluster in yeast.
AB  - Metabolic gene clusters--functionally related and physically clustered genes--are
      a common feature of some eukaryotic genomes. Two hypotheses have been advanced to
      explain the origin and maintenance of metabolic gene clusters: coordinated gene
      expression and genetic linkage. Here we test the hypothesis that selection for
      coordinated gene expression underlies the clustering of GAL genes in the yeast
      genome. We find that, although clustering coordinates the expression of GAL1 and
      GAL10, disrupting the GAL cluster does not impair fitness, suggesting that other
      mechanisms, such as genetic linkage, drive the origin and maintenance metabolic
      gene clusters.

PMID- 21966487
TI  - Genome-scale analysis of Mycoplasma agalactiae loci involved in interaction with
      host cells.
AB  - Mycoplasma agalactiae is an important pathogen of small ruminants, in which it
      causes contagious agalactia. It belongs to a large group of "minimal bacteria"
      with a small genome and reduced metabolic capacities that are dependent on their
      host for nutrients. Mycoplasma survival thus relies on intimate contact with host
      cells, but little is known about the factors involved in these interactions or in
      the more general infectious process. To address this issue, an assay based on
      goat epithelial and fibroblastic cells was used to screen a M. agalactiae
      knockout mutant library. Mutants with reduced growth capacities in cell culture
      were selected and 62 genomic loci were identified as contributing to this
      phenotype. As expected for minimal bacteria, "transport and metabolism" was the
      functional category most commonly implicated in this phenotype, but 50% of the
      selected mutants were disrupted in coding sequences (CDSs) with unknown
      functions, with surface lipoproteins being most commonly represented in this
      category. Since mycoplasmas lack a cell wall, lipoproteins are likely to be
      important in interactions with the host. A few intergenic regions were also
      identified that may act as regulatory sequences under co-culture conditions.
      Interestingly, some mutants mapped to gene clusters that are highly conserved
      across mycoplasma species but located in different positions. One of these
      clusters was found in a transcriptionally active region of the M. agalactiae
      chromosome, downstream of a cryptic promoter. A possible scenario for the
      evolution of these loci is discussed. Finally, several CDSs identified here are
      conserved in other important pathogenic mycoplasmas, and some were involved in
      horizontal gene transfer with phylogenetically distant species. These results
      provide a basis for further deciphering functions mediating mycoplasma-host
      interactions.

PMID- 21966488
TI  - A scoring model based on neutrophil to lymphocyte ratio predicts recurrence of
      HBV-associated hepatocellular carcinoma after liver transplantation.
AB  - BACKGROUND: Neutrophil to lymphocyte ratio (NLR) has been proposed to predict
      prognosis of hepatocellular carcinoma (HCC). However, the cut-off values are
      empirical. We determined the optimal cut-off value to predict HCC recurrence
      after liver transplantation (LT) and further established a scoring model based on
      NLR. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the outcome of 101 HBV
      associated HCC patients undergoing LT. Preoperative risk factors for tumor
      recurrence were evaluated by univariate analysis. By using ROC analysis, NLR>=3
      was considered elevated. The disease-free survival (DFS) and overall survival
      (OS) for patients with high NLR was significantly worse than that for patients
      with normal NLR (the 5-year DFS and OS of 28.5% and 19.5% vs. 64.9% and 61.8%,
      respectively; P<0.001). Univariate analysis revealed that tumor size >5 cm, tumor
      number >3, macrovascular invasion, AFP>=400 ug/L, NLR>=3, and HBV-DNA level >5
      log10 copies/mL were preoperative predictors of DFS. Cox regression analysis
      showed macrovascular invasion, tumor number, and high NLR were independent
      prognostic factors. We then established a preoperative prognostic score based on
      multivariate analysis. Each factor was given a score of 1. Area under the ROC
      curve of the score was 0.781. All nine patients with score 3 developed recurrence
      within 6 months after LT. Of 71 patients without vascular invasion, three
      patients with both tumor number >3 and NLR>=3 developed recurrence within 14
      months after LT while the 5-year DFS and OS for patients with a score of 0 or 1
      were 68.1% and 62.8%, respectively. CONCLUSIONS/SIGNIFICANCE: Preoperative
      elevated NLR significantly increases the risk of recurrence in patients underwent
      LT for HCC. Patients with both NLR>=3 and tumor number >3 are not a good
      indication for LT. Our score model may aid in the selection of patients that
      would most benefit from transplantation for HCC.

PMID- 21966489
TI  - Seasonal and temperature-associated increases in gram-negative bacterial
      bloodstream infections among hospitalized patients.
AB  - BACKGROUND: Knowledge of seasonal trends in hospital-associated infection
      incidence may improve surveillance and help guide the design and evaluation of
      infection prevention interventions. We estimated seasonal variation in the
      frequencies of inpatient bloodstream infections (BSIs) caused by common bacterial
      pathogens and examined associations of monthly BSI frequencies with ambient
      outdoor temperature, precipitation, and humidity levels. METHODS: A database
      containing blood cultures from 132 U.S. hospitals collected between January 1999
      and September 2006 was assembled. The database included monthly counts of
      inpatient blood cultures positive for several clinically important Gram-negative
      bacteria (Acinetobacter spp, Escherichia coli, Klebsiella pneumoniae, and
      Pseudomonas aeruginosa) and Gram-positive bacteria (Enterococcus spp and
      Staphylococcus aureus). Monthly mean temperature, total precipitation, and mean
      relative humidity in the postal ZIP codes of participating hospitals were
      obtained from national meteorological databases. RESULTS: A total of 211,697
      inpatient BSIs were reported during 9,423 hospital-months. Adjusting for long
      term trends, BSIs caused by each gram-negative organism examined were more
      frequent in summer months compared with winter months, with increases ranging
      from 12.2% for E. coli (95% CI 9.2-15.4) to 51.8% for Acinetobacter (95% CI 41.1
      63.2). Summer season was associated with 8.7% fewer Enterococcus BSIs (95% CI
      11.0-5.8) and no significant change in S. aureus BSI frequency relative to
      winter. Independent of season, monthly humidity, monthly precipitation, and long
      term trends, each 5.6 degrees C (10 degrees F) rise in mean monthly temperature
      corresponded to increases in gram-negative bacterial BSI frequencies ranging
      between 3.5% for E. coli (95% CI 2.1-4.9) to 10.8% for Acinetobacter (95% CI 6.9
      14.7). The same rise in mean monthly temperature corresponded to an increase of
      2.2% in S. aureus BSI frequency (95% CI 1.3-3.2) but no significant change in
      Enterococcus BSI frequency. CONCLUSIONS: Summer season and higher mean monthly
      outdoor temperature are associated with substantially increased frequency of
      BSIs, particularly among clinically important gram-negative bacteria.

PMID- 21966490
TI  - pH landscapes in a novel five-species model of early dental biofilm.
AB  - BACKGROUND: Despite continued preventive efforts, dental caries remains the most
      common disease of man. Organic acids produced by microorganisms in dental plaque
      play a crucial role for the development of carious lesions. During early stages
      of the pathogenetic process, repeated pH drops induce changes in microbial
      composition and favour the establishment of an increasingly acidogenic and
      aciduric microflora. The complex structure of dental biofilms, allowing for a
      multitude of different ecological environments in close proximity, remains
      largely unexplored. In this study, we designed a laboratory biofilm model that
      mimics the bacterial community present during early acidogenic stages of the
      caries process. We then performed a time-resolved microscopic analysis of the
      extracellular pH landscape at the interface between bacterial biofilm and
      underlying substrate. METHODOLOGY/PRINCIPAL FINDINGS: Strains of Streptococcus
      oralis, Streptococcus sanguinis, Streptococcus mitis, Streptococcus downei and
      Actinomyces naeslundii were employed in the model. Biofilms were grown in flow
      channels that allowed for direct microscopic analysis of the biofilms in situ.
      The architecture and composition of the biofilms were analysed using fluorescence
      in situ hybridization and confocal laser scanning microscopy. Both biofilm
      structure and composition were highly reproducible and showed similarity to in
      vivo-grown dental plaque. We employed the pH-sensitive ratiometric probe C-SNARF
      4 to perform real-time microscopic analyses of the biofilm pH in response to
      salivary solutions containing glucose. Anaerobic glycolysis in the model biofilms
      created a mildly acidic environment. Decrease in pH in different areas of the
      biofilms varied, and distinct extracellular pH-microenvironments were conserved
      over several hours. CONCLUSIONS/SIGNIFICANCE: The designed biofilm model
      represents a promising tool to determine the effect of potential therapeutic
      agents on biofilm growth, composition and extracellular pH. Ratiometric pH
      analysis using C-SNARF-4 gives detailed insight into the pH landscape of living
      biofilms and contributes to our general understanding of metabolic processes in
      in-vivo-grown bacterial biofilms.

PMID- 21966491
TI  - Engagement of overexpressed Her2 with GEP100 induces autonomous invasive
      activities and provides a biomarker for metastases of lung adenocarcinoma.
AB  - Overexpression of Her2/ErbB2/Neu in cancer is often correlated with recurrent
      distant metastasis, although the mechanism still remains largely elusive. We have
      previously shown that EGFR, when tyrosine-phosphorylated, binds to GEP100/BRAG2
      to activate Arf6, which induces cancer invasion and metastasis. We now show that
      overexpressed Her2 in lung adenocarcinoma cells also employs GEP100. Like EGFR
      GEP100 binding, this association is primarily mediated by the pleckstrin homology
      (PH) domain of GEP100 and Tyr1139/Tyr1196 of Her2. Tyr1139/Tyr1196 are
      autonomously phosphorylated, when Her2 is overexpressed. Accordingly, invasive
      activities mediated by the Her2-GEP100 pathway are not dependent on external
      factors. Blocking Her2-GEP100 binding, as well as its signaling pathway all
      inhibit cancer invasive activities. Moreover, our clinical study indicates that
      co-overexpression of Her2 with GEP100 in primary lung adenocarcinomas of patients
      is correlated with the presence of their node-metastasis with a statistical
      significance. Since the GEP100 PH domain interacts with both Her2 and EGFR,
      targeting this domain may provide novel cancer therapeutics.

PMID- 21966492
TI  - Time-lapse imaging reveals symmetric neurogenic cell division of GFAP-expressing
      progenitors for expansion of postnatal dentate granule neurons.
AB  - Granule cells in the hippocampus, a region critical for memory and learning, are
      generated mainly during the early postnatal period but neurogenesis continues in
      adulthood. Postnatal neuronal production is carried out by primary progenitors
      that express glial fibrillary acidic protein (GFAP) and they are assumed to
      function as stem cells. A central question regarding postnatal dentate
      neurogenesis is how astrocyte-like progenitors produce neurons. To reveal cell
      division patterns and the process of neuronal differentiation of astrocyte-like
      neural progenitors, we performed time-lapse imaging in cultured hippocampal
      slices from early postnatal transgenic mice with mouse GFAP promoter-controlled
      enhanced green fluorescent protein (mGFAP-eGFP Tg mice) in combination with a
      retrovirus carrying a red fluorescent protein gene. Our results showed that the
      majority of GFAP-eGFP+ progenitor cells that express GFAP, Sox2 and nestin
      divided symmetrically to produce pairs of GFAP+ cells (45%) or pairs of neuron
      committed cells (45%), whereas a minority divided asymmetrically to generate
      GFAP+ cells and neuron-committed cells (10%). The present results suggest that a
      substantial number of GFAP-expressing progenitors functions as transient
      amplifying progenitors, at least in an early postnatal dentate gyrus, although a
      small population appears to be stem cell-like progenitors. From the present data,
      we discuss possible cell division patterns of adult GFAP+ progenitors.

PMID- 21966493
TI  - Accounting for diffusion in agent based models of reaction-diffusion systems with
      application to cytoskeletal diffusion.
AB  - Diffusion plays a key role in many biochemical reaction systems seen in nature.
      Scenarios where diffusion behavior is critical can be seen in the cell and
      subcellular compartments where molecular crowding limits the interaction between
      particles. We investigate the application of a computational method for modeling
      the diffusion of molecules and macromolecules in three-dimensional solutions
      using agent based modeling. This method allows for realistic modeling of a system
      of particles with different properties such as size, diffusion coefficients, and
      affinity as well as the environment properties such as viscosity and geometry.
      Simulations using these movement probabilities yield behavior that mimics natural
      diffusion. Using this modeling framework, we simulate the effects of molecular
      crowding on effective diffusion and have validated the results of our model using
      Langevin dynamics simulations and note that they are in good agreement with
      previous experimental data. Furthermore, we investigate an extension of this
      framework where single discrete cells can contain multiple particles of varying
      size in an effort to highlight errors that can arise from discretization that
      lead to the unnatural behavior of particles undergoing diffusion. Subsequently,
      we explore various algorithms that differ in how they handle the movement of
      multiple particles per cell and suggest an algorithm that properly accommodates
      multiple particles of various sizes per cell that can replicate the natural
      behavior of these particles diffusing. Finally, we use the present modeling
      framework to investigate the effect of structural geometry on the directionality
      of diffusion in the cell cytoskeleton with the observation that parallel
      orientation in the structural geometry of actin filaments of filopodia and the
      branched structure of lamellipodia can give directionality to diffusion at the
      filopodia-lamellipodia interface.

PMID- 21966494
TI  - The value of success: acquiring gains, avoiding losses, and simply being
      successful.
AB  - A large network of spatially contiguous, yet anatomically distinct regions in
      medial frontal cortex is involved in reward processing. Although it is clear
      these regions play a role in critical aspects of reward-related learning and
      decision-making, the individual contributions of each component remains unclear.
      We explored dissociations in reward processing throughout several key regions in
      the reward system and aimed to clarify the nature of previously observed outcome
      related activity in a portion of anterior medial orbitofrontal cortex (mOFC).
      Specifically, we tested whether activity in anterior mOFC was related to
      processing successful actions, such that this region would respond similarly to
      rewards with and without tangible benefits, or whether this region instead
      encoded only quantifiable outcome values (e.g., money). Participants performed a
      task where they encountered monetary gains and losses (and non-gains and non
      losses) during fMRI scanning. Critically, in addition to the outcomes with
      monetary consequences, the task included trials that provided outcomes without
      tangible benefits (participants were simply told that they were correct or
      incorrect). We found that anterior mOFC responded to all successful outcomes
      regardless of whether they carried tangible benefits (monetary gains and non
      losses) or not (controls). These results support the hypothesis that anterior
      mOFC processes rewards in terms of a common currency and is capable of providing
      reward-based signals for everything we value, whether it be primary or secondary
      rewards or simply a successful experience without objectively quantifiable
      benefits.

PMID- 21966495
TI  - A single peroxisomal targeting signal mediates matrix protein import in diatoms.
AB  - Peroxisomes are single membrane bound compartments. They are thought to be
      present in almost all eukaryotic cells, although the bulk of our knowledge about
      peroxisomes has been generated from only a handful of model organisms.
      Peroxisomal matrix proteins are synthesized cytosolically and posttranslationally
      imported into the peroxisomal matrix. The import is generally thought to be
      mediated by two different targeting signals. These are respectively recognized by
      the two import receptor proteins Pex5 and Pex7, which facilitate transport across
      the peroxisomal membrane. Here, we show the first in vivo localization studies of
      peroxisomes in a representative organism of the ecologically relevant group of
      diatoms using fluorescence and transmission electron microscopy. By expression of
      various homologous and heterologous fusion proteins we demonstrate that targeting
      of Phaeodactylum tricornutum peroxisomal matrix proteins is mediated only by PTS1
      targeting signals, also for proteins that are in other systems imported via a
      PTS2 mode of action. Additional in silico analyses suggest this surprising
      finding may also apply to further diatoms. Our data suggest that loss of the PTS2
      peroxisomal import signal is not reserved to Caenorhabditis elegans as a single
      exception, but has also occurred in evolutionary divergent organisms. Obviously,
      targeting switching from PTS2 to PTS1 across different major eukaryotic groups
      might have occurred for different reasons. Thus, our findings question the
      widespread assumption that import of peroxisomal matrix proteins is generally
      mediated by two different targeting signals. Our results implicate that there
      apparently must have been an event causing the loss of one targeting signal even
      in the group of diatoms. Different possibilities are discussed that indicate
      multiple reasons for the detected targeting switching from PTS2 to PTS1.

PMID- 21966496
TI  - Antifungal activity of microbial secondary metabolites.
AB  - Secondary metabolites are well known for their ability to impede other
      microorganisms. Reanalysis of a screen of natural products using the
      Caenorhabditis elegans-Candida albicans infection model identified twelve
      microbial secondary metabolites capable of conferring an increase in survival to
      infected nematodes. In this screen, the two compound treatments conferring the
      highest survival rates were members of the epipolythiodioxopiperazine (ETP)
      family of fungal secondary metabolites, acetylgliotoxin and a derivative of
      hyalodendrin. The abundance of fungal secondary metabolites indentified in this
      screen prompted further studies investigating the interaction between
      opportunistic pathogenic fungi and Aspergillus fumigatus, because of the ability
      of the fungus to produce a plethora of secondary metabolites, including the well
      studied ETP gliotoxin. We found that cell-free supernatant of A. fumigatus was
      able to inhibit the growth of Candida albicans through the production of a
      secreted product. Comparative studies between a wild-type and an A. fumigatus
      DeltagliP strain unable to synthesize gliotoxin demonstrate that this secondary
      metabolite is the major factor responsible for the inhibition. Although toxic to
      organisms, gliotoxin conferred an increase in survival to C. albicans-infected C.
      elegans in a dose dependent manner. As A. fumigatus produces gliotoxin in vivo,
      we propose that in addition to being a virulence factor, gliotoxin may also
      provide an advantage to A. fumigatus when infecting a host that harbors other
      opportunistic fungi.

PMID- 21966497
TI  - Contribution of chronic disease to the burden of disability.
AB  - BACKGROUND: Population ageing is expected to lead to strong increases in the
      number of persons with one or more disabilities, which may result in substantial
      declines in the quality of life. To reduce the burden of disability and to
      prevent concomitant declines in the quality of life, one of the first steps is to
      establish which diseases contribute most to the burden. Therefore, this paper
      aims to determine the contribution of specific diseases to the prevalence of
      disability and to years lived with disability, and to assess whether large
      contributions are due to a high disease prevalence or a high disabling impact.
      METHODOLOGY/PRINCIPAL FINDINGS: Data from the Dutch POLS-survey (Permanent
      Onderzoek Leefsituatie, 2001-2007) were analyzed. Using additive regression and
      accounting for co-morbidity, the disabling impact of selected chronic diseases
      was calculated, and the prevalence and years lived with ADL and mobility
      disabilities were partitioned into contributions of specific disease.
      Musculoskeletal and cardiovascular disease contributed most to the burden of
      disability, but chronic non-specific lung disease (males) and diabetes (females)
      also contributed much. Within the musculoskeletal and cardiovascular disease
      groups, back pain, peripheral vascular disease and stroke contributed
      particularly by their high disabling impact. Arthritis and heart disease were
      less disabling but contributed substantially because of their high prevalence.
      The disabling impact of diseases was particularly high among persons older than
      80. CONCLUSIONS/SIGNIFICANCE: To reduce the burden of disability, the extent
      diseases such as back pain, peripheral vascular disease and stroke lead to
      disability should be reduced, particularly among the oldest old. But also
      moderately disabling diseases with a high prevalence, such as arthritis and heart
      disease, should be targeted.

PMID- 21966498
TI  - Growth strategies of tropical tree species: disentangling light and size effects.
AB  - An understanding of the drivers of tree growth at the species level is required
      to predict likely changes of carbon stocks and biodiversity when environmental
      conditions change. Especially in species-rich tropical forests, it is largely
      unknown how species differ in their response of growth to resource availability
      and individual size. We use a hierarchical bayesian approach to quantify the
      impact of light availability and tree diameter on growth of 274 woody species in
      a 50-ha long-term forest census plot in Barro Colorado Island, Panama. Light
      reaching each individual tree was estimated from yearly vertical censuses of
      canopy density. The hierarchical bayesian approach allowed accounting for
      different sources of error, such as negative growth observations, and including
      rare species correctly weighted by their abundance. All species grew faster at
      higher light. Exponents of a power function relating growth to light were mostly
      between 0 and 1. This indicates that nearly all species exhibit a decelerating
      increase of growth with light. In contrast, estimated growth rates at
      standardized conditions (5 cm dbh, 5% light) varied over a 9-fold range and
      reflect strong growth-strategy differentiation between the species. As a
      consequence, growth rankings of the species at low (2%) and high light (20%) were
      highly correlated. Rare species tended to grow faster and showed a greater
      sensitivity to light than abundant species. Overall, tree size was less important
      for growth than light and about half the species were predicted to grow faster in
      diameter when bigger or smaller, respectively. Together light availability and
      tree diameter only explained on average 12% of the variation in growth rates.
      Thus, other factors such as soil characteristics, herbivory, or pathogens may
      contribute considerably to shaping tree growth in the tropics.

PMID- 21966500
TI  - Complete sequencing of the bla(NDM-1)-positive IncA/C plasmid from Escherichia
      coli ST38 isolate suggests a possible origin from plant pathogens.
AB  - The complete sequence of the plasmid pNDM-1_Dok01 carrying New Delhi metallo-beta
      lactamase (NDM-1) was determined by whole genome shotgun sequencing using
      Escherichia coli strain NDM-1_Dok01 (multilocus sequence typing type: ST38) and
      the transconjugant E. coli DH10B. The plasmid is an IncA/C incompatibility type
      composed of 225 predicted coding sequences in 195.5 kb and partially shares a
      sequence with bla(CMY-2)-positive IncA/C plasmids such as E. coli AR060302
      pAR060302 (166.5 kb) and Salmonella enterica serovar Newport pSN254 (176.4 kb).
      The bla(NDM-1) gene in pNDM-1_Dok01 is terminally flanked by two IS903 elements
      that are distinct from those of the other characterized NDM-1 plasmids,
      suggesting that the bla(NDM-1) gene has been broadly transposed, together with
      various mobile elements, as a cassette gene. The chaperonin groES and groEL genes
      were identified in the bla(NDM-1)-related composite transposon, and phylogenetic
      analysis and guanine-cytosine content (GC) percentage showed similarities to the
      homologs of plant pathogens such as Pseudoxanthomonas and Xanthomonas spp.,
      implying that plant pathogens are the potential source of the bla(NDM-1) gene.
      The complete sequence of pNDM-1_Dok01 suggests that the bla(NDM-1) gene was
      acquired by a novel composite transposon on an extensively disseminated IncA/C
      plasmid and transferred to the E. coli ST38 isolate.

PMID- 21966499
TI  - Substance P induces rapid and transient membrane blebbing in U373MG cells in a
      p21-activated kinase-dependent manner.
AB  - U373MG astrocytoma cells endogenously express the full-length neurokinin 1
      receptor (NK1R). Substance P (SP), the natural ligand for NK1R, triggers rapid
      and transient membrane blebbing and we report that these morphological changes
      have different dynamics and intracellular signaling as compared to the changes
      that we have previously described in HEK293-NK1R cells. In both cell lines, the
      SP-induced morphological changes are Gq-independent, and they require the Rho,
      Rho-associated coiled-coil kinase (ROCK) signaling pathway. Using confocal
      microscopy we have demonstrated that tubulin is phosphorylated subsequent to cell
      stimulation with SP and that tubulin accumulates inside the blebs. Colchicine, a
      tubulin polymerization inhibitor, blocked SP-induced blebbing in U373MG but not
      in HEK293-NK1R cells. Although p21-activated kinase (PAK) is expressed in both
      cell lines, SP induced rapid phosphorylation of PAK in U373MG, but failed to
      phosphorylate PAK in HEK293-NK1R cells. The cell-permeable Rho inhibitor C3
      transferase inhibited SP-induced PAK phosphorylation, but the ROCK inhibitor
      Y27632 had no effect on PAK phosphorylation, suggesting that Rho activates PAK in
      a ROCK-independent manner. Our study demonstrates that SP triggers rapid changes
      in cell morphology mediated by distinct intracellular signaling mechanisms in
      U373MG versus HEK293-NK1R cells.

PMID- 21966501
TI  - Aging negatively affects estrogens-mediated effects on nitric oxide
      bioavailability by shifting ERalpha/ERbeta balance in female mice.
AB  - AIMS: Aging is among the major causes for the lack of cardiovascular protection
      by estrogen (E2) during postmenopause. Our study aims to determine the mechanisms
      whereby aging changes E2 effects on nitric oxide (NO) production in a mouse model
      of accelerated senescence (SAM). METHODS AND RESULTS: Although we found no
      differences on NO production in females SAM prone (SAMP, aged) compared to SAM
      resistant (SAMR, young), by either DAF-2 fluorescence or plasmatic
      nitrite/nitrate (NO2/NO3), in both cases, E2 treatment increased NO production in
      SAMR but had no effect in SAMP. Those results are in agreement with changes of
      eNOS protein and gene expression. E2 up-regulated eNOS expression in SAMR but not
      in SAMP. E2 is also known to increase NO by decreasing its catabolism by
      superoxide anion (O(2)(-)). Interestingly, E2 treatment decreased O(2)(-)
      production in young females, while increased O(2)(-) in aged ones. Furthermore,
      we observed that aging changed expression ratio of estrogen receptors
      (ERbeta/ERalpha) and levels of DNA methylation. Increased ratio ERbeta/ERalpha in
      aged females is associated to a lack of estrogen modulation of NO production and
      with a reversal in its antioxidant effect to a pro-oxidant profile. CONCLUSIONS:
      Together, our data suggest that aging has detrimental effects on E2-mediated
      benefits on NO bioavailability, partially by affecting the ability of E2 to
      induce up regulation of eNOS and decrease of O(2)(-). These modifications may be
      associated to aging-mediated modifications on global DNA methylation status, but
      not to a specific methylation at 5'flanking region of ERalpha gene.

PMID- 21966502
TI  - Combining antigen-based therapy with GABA treatment synergistically prolongs
      survival of transplanted beta-cells in diabetic NOD mice.
AB  - Antigen-based therapies (ABTs) very effectively prevent the development of type 1
      diabetes (T1D) when given to young nonobese diabetic (NOD) mice, however, they
      have little or no ability to reverse hyperglycemia in newly diabetic NOD mice.
      More importantly, ABTs have not yet demonstrated an ability to effectively
      preserve residual beta-cells in individuals newly diagnosed with type 1 diabetes
      (T1D). Accordingly, there is great interest in identifying new treatments that
      can be combined with ABTs to safely protect beta-cells in diabetic animals. The
      activation of gamma-aminobutyric acid (GABA) receptors (GABA-Rs) on immune cells
      has been shown to prevent T1D, experimental autoimmune encephalomyelitis (EAE)
      and rheumatoid arthritis in mouse models. Based on GABA's ability to inhibit
      different autoimmune diseases and its safety profile, we tested whether the
      combination of ABT with GABA treatment could prolong the survival of transplanted
      beta-cells in newly diabetic NOD mice. Newly diabetic NOD mice were untreated, or
      given GAD/alum (20 or 100 ug) and placed on plain drinking water, or water
      containing GABA (2 or 6 mg/ml). Twenty-eight days later, they received syngenic
      pancreas grafts and were monitored for the recurrence of hyperglycemia.
      Hyperglycemia reoccurred in the recipients given plain water, GAD monotherapy,
      GABA monotherapy, GAD (20 ug)+GABA (2 mg/ml), GAD (20 ug)+GABA (6 mg/ml) and GAD
      (100 ug)+GABA (6 mg/ml) about 1, 2-3, 3, 2-3, 3-8 and 10-11 weeks post
      transplantation, respectively. Thus, combined GABA and ABT treatment had a
      synergistic effect in a dose-dependent fashion. These findings suggest that co
      treatment with GABA (or other GABA-R agonists) may provide a new strategy to
      safely enhance the efficacy of other therapeutics designed to prevent or reverse
      T1D, as well as other T cell-mediated autoimmune diseases.

PMID- 21966503
TI  - Oral treatment with gamma-aminobutyric acid improves glucose tolerance and
      insulin sensitivity by inhibiting inflammation in high fat diet-fed mice.
AB  - Adipocyte and beta-cell dysfunction and macrophage-related chronic inflammation
      are critical for the development of obesity-related insulin resistance and type 2
      diabetes mellitus (T2DM), which can be negatively regulated by Tregs. Our
      previous studies and those of others have shown that activation of gamma
      aminobutyric acid (GABA) receptors inhibits inflammation in mice. However,
      whether GABA could modulate high fat diet (HFD)-induced obesity, glucose
      intolerance and insulin resistance has not been explored. Here, we show that
      although oral treatment with GABA does not affect water and food consumption it
      inhibits the HFD-induced gain in body weights in C57BL/6 mice. Furthermore, oral
      treatment with GABA significantly reduced the concentrations of fasting blood
      glucose, and improved glucose tolerance and insulin sensitivity in the HFD-fed
      mice. More importantly, after the onset of obesity and T2DM, oral treatment with
      GABA inhibited the continual HFD-induced gain in body weights, reduced the
      concentrations of fasting blood glucose and improved glucose tolerance and
      insulin sensitivity in mice. In addition, oral treatment with GABA reduced the
      epididymal fat mass, adipocyte size, and the frequency of macrophage infiltrates
      in the adipose tissues of HFD-fed mice. Notably, oral treatment with GABA
      significantly increased the frequency of CD4(+)Foxp3(+) Tregs in mice.
      Collectively, our data indicated that activation of peripheral GABA receptors
      inhibited the HFD-induced glucose intolerance, insulin resistance, and obesity by
      inhibiting obesity-related inflammation and up-regulating Treg responses in vivo.
      Given that GABA is safe for human consumption, activators of GABA receptors may
      be valuable for the prevention of obesity and intervention of T2DM in the clinic.

PMID- 21966504
TI  - Motivational state and reward content determine choice behavior under risk in
      mice.
AB  - Risk is a ubiquitous feature of the environment for most organisms, who must
      often choose between a small and certain reward and a larger but less certain
      reward. To study choice behavior under risk in a genetically well characterized
      species, we trained mice (C57BL/6) on a discrete trial, concurrent-choice task in
      which they must choose between two levers. Pressing one lever (safe choice) is
      always followed by a small reward. Pressing the other lever (risky choice) is
      followed by a larger reward, but only on some of the trials. The overall payoff
      is the same on both levers. When mice were not food deprived, they were
      indifferent to risk, choosing both levers with equal probability regardless of
      the level of risk. In contrast, following food or water deprivation, mice earning
      10% sucrose solution were risk-averse, though the addition of alcohol to the
      sucrose solution dose-dependently reduced risk aversion, even before the mice
      became intoxicated. Our results falsify the budget rule in optimal foraging
      theory often used to explain behavior under risk. Instead, they suggest that the
      overall demand or desired amount for a particular reward determines risk
      preference. Changes in motivational state or reward identity affect risk
      preference by changing demand. Any manipulation that increases the demand for a
      reward also increases risk aversion, by selectively increasing the frequency of
      safe choices without affecting frequency of risky choices.

PMID- 21966505
TI  - Comparison of electronic data capture (EDC) with the standard data capture method
      for clinical trial data.
AB  - BACKGROUND: Traditionally, clinical research studies rely on collecting data with
      case report forms, which are subsequently entered into a database to create
      electronic records. Although well established, this method is time-consuming and
      error-prone. This study compares four electronic data capture (EDC) methods with
      the conventional approach with respect to duration of data capture and accuracy.
      It was performed in a West African setting, where clinical trials involve data
      collection from urban, rural and often remote locations. METHODOLOGY/PRINCIPAL
      FINDINGS: Three types of commonly available EDC tools were assessed in face-to
      face interviews; netbook, PDA, and tablet PC. EDC performance during telephone
      interviews via mobile phone was evaluated as a fourth method. The Graeco Latin
      square study design allowed comparison of all four methods to standard paper
      based recording followed by data double entry while controlling simultaneously
      for possible confounding factors such as interview order, interviewer and
      interviewee. Over a study period of three weeks the error rates decreased
      considerably for all EDC methods. In the last week of the study the data accuracy
      for the netbook (5.1%, CI95%: 3.5-7.2%) and the tablet PC (5.2%, CI95%: 3.7-7.4%)
      was not significantly different from the accuracy of the conventional paper-based
      method (3.6%, CI95%: 2.2-5.5%), but error rates for the PDA (7.9%, CI95%: 6.0
      10.5%) and telephone (6.3%, CI95% 4.6-8.6%) remained significantly higher. While
      EDC-interviews take slightly longer, data become readily available after
      download, making EDC more time effective. Free text and date fields were
      associated with higher error rates than numerical, single select and skip fields.
      CONCLUSIONS: EDC solutions have the potential to produce similar data accuracy
      compared to paper-based methods. Given the considerable reduction in the time
      from data collection to database lock, EDC holds the promise to reduce research
      associated costs. However, the successful implementation of EDC requires
      adjustment of work processes and reallocation of resources.

PMID- 21966506
TI  - AMPA receptor regulation at the mRNA and protein level in rat primary cortical
      cultures.
AB  - Ionotropic glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
      (AMPA) receptors are the major mediators of fast synaptic neurotransmission. In
      this work, we used primary cortical cultures from rats as a model system to study
      AMPA receptor regulation during in vitro cell maturation and after synaptic
      activity modifications. The levels of AMPA receptor mRNA and protein, along with
      the alternative splicing and RNA editing of the AMPA receptor subunit (GluR1-4)
      mRNAs, were analyzed in immature (DIV5) and mature (DIV26) rat neuronal cultures.
      We observed an increase in the expression of all four AMPA receptor subunits
      during in vitro neuronal maturation. This finding might be due to the formation
      of new synapses between neurons during the development of a complex neuronal
      network. We also analyzed the effects of stimulation (KCl and glutamate) and
      inhibition (APV/TTX) on rat mature neuronal cultures (DIV26): stimulation with
      KCl led to an overall down-regulation of GluR1 and GluR3 AMPA receptor subunits
      and an up-regulation of the GluR2 subunit. Similarly, glutamate treatment induced
      a significant down-regulation of GluR1 together with an up-regulation of GluR2.
      In contrast, the chronic blockade of neuronal activity that resulted from APV/TTX
      treatment up-regulated GluR1 and GluR3 with a parallel down-regulation of GluR2
      and GluR4. RNA editing at the R/G site increased during neuronal cell maturation
      for all AMPA receptors (from 8-39% at DIV5 to 28-67% at DIV26). Unexpectedly, all
      the treatments tested induced a marked reduction (ranging from -9% to -52%) of
      R/G editing levels in mature neurons, primarily for the mRNA flip variant. In
      summary, we showed that cultured rat cortical neurons are able to vary the
      stoichiometric ratios of the AMPA receptor subunits and to control post
      transcriptional processes to adapt fast synaptic transmission under different
      environmental conditions.

PMID- 21966507
TI  - Inferring species trees from gene trees in a radiation of California trapdoor
      spiders (Araneae, Antrodiaetidae, Aliatypus).
AB  - BACKGROUND: The California Floristic Province is a biodiversity hotspot,
      reflecting a complex geologic history, strong selective gradients, and a
      heterogeneous landscape. These factors have led to high endemic diversity across
      many lifeforms within this region, including the richest diversity of mygalomorph
      spiders (tarantulas, trapdoor spiders, and kin) in North America. The trapdoor
      spider genus Aliatypus encompasses twelve described species, eleven of which are
      endemic to California. Several Aliatypus species show disjunct distributional
      patterns in California (some are found on both sides of the vast Central Valley),
      and the genus as a whole occupies an impressive variety of habitats.
      METHODOLOGY/PRINCIPAL FINDINGS: We collected specimens from 89 populations
      representing all described species. DNA sequence data were collected from seven
      gene regions, including two newly developed for spider systematics. Bayesian
      inference (in individual gene tree and species tree approaches) recovered a
      general "3 clade" structure for the genus (A. gulosus, californicus group, erebus
      group), with three other phylogenetically isolated species differing slightly in
      position across different phylogenetic analyses. Because of extremely high
      intraspecific divergences in mitochondrial COI sequences, the relatively slowly
      evolving 28S rRNA gene was found to be more useful than mitochondrial data for
      identification of morphologically indistinguishable immatures. For multiple
      species spanning the Central Valley, explicit hypothesis testing suggests a lack
      of monophyly for regional populations (e.g., western Coast Range populations).
      Phylogenetic evidence clearly shows that syntopy is restricted to distant
      phylogenetic relatives, consistent with ecological niche conservatism.
      CONCLUSIONS/SIGNIFICANCE: This study provides fundamental insight into a
      radiation of trapdoor spiders found in the biodiversity hotspot of California.
      Species relationships are clarified and undescribed lineages are discovered, with
      more geographic sampling likely to lead to additional species diversity. These
      dispersal-limited taxa provide novel insight into the biogeography and Earth
      history processes of California.

PMID- 21966508
TI  - Differential modulation of ATP-induced P2X7-associated permeabilities to cations
      and anions of macrophages by infection with Leishmania amazonensis.
AB  - Leishmania and other parasites display several mechanisms to subvert host immune
      cell function in order to achieve successful infection. The ATP receptor P2X7, an
      agonist-gated cation channel widely expressed in macrophages and other cells of
      the immune system, is also coupled to inflammasome activation, IL-1 beta
      secretion, production of reactive oxygen species, cell death and the induction of
      the permeabilization of the plasma membrane to molecules of up to 900 Da. P2X7
      receptors can function as an effective microbicidal triggering receptor in
      macrophages infected with several microorganisms including Mycobacteria
      tuberculosis, Chlamydia and Leishmania. We have previously shown that its
      expression is up-regulated in macrophages infected with L. amazonensis and that
      infected cells also display an increase in P2X7-induced apoptosis and membrane
      permeabilization to some anionic fluorescent dyes. In an independent study we
      recently showed that the phenomenon of macrophage membrane permeabilization can
      involve at least two distinct pathways for cations and anions respectively. Here,
      we re-addressed the effects of ATP-induced P2X7-associated phenomena in
      macrophages infected with L. amazonensis and demonstrated that the P2X7
      associated dye uptake mechanisms are differentially modulated. While the membrane
      permeabilization for anionic dyes is up-modulated, as previously described, the
      uptake of cationic dyes is strongly down-modulated. These results unveil new
      characteristics of two distinct permeabilization mechanisms associated with P2X7
      receptors in macrophages and provide the first evidence indicating that these
      pathways can be differentially modulated in an immunologically relevant
      situation. The possible importance of these results to the L. amazonensis escape
      mechanism is discussed.

PMID- 21966509
TI  - Structural insights into the mechanism of protein O-fucosylation.
AB  - Protein O-fucosylation is an essential post-translational modification, involved
      in the folding of target proteins and in the role of these target proteins during
      embryonic development and adult tissue homeostasis, among other things. Two
      different enzymes are responsible for this modification, Protein O
      fucosyltransferase 1 and 2 (POFUT1 and POFUT2, respectively). Both proteins have
      been characterised biologically and enzymatically but nothing is known at the
      molecular or structural level. Here we describe the first crystal structure of a
      catalytically functional POFUT1 in an apo-form and in complex with GDP-fucose and
      GDP. The enzyme belongs to the GT-B family and is not dependent on manganese for
      activity. GDP-fucose/GDP is localised in a conserved cavity connected to a large
      solvent exposed pocket, which we show is the binding site of epidermal growth
      factor (EGF) repeats in the extracellular domain of the Notch Receptor. Through
      both mutational and kinetic studies we have identified which residues are
      involved in binding and catalysis and have determined that the Arg240 residue is
      a key catalytic residue. We also propose a novel S(N)1-like catalytic mechanism
      with formation of an intimate ion pair, in which the glycosidic bond is cleaved
      before the nucleophilic attack; and theoretical calculations at a DFT (B3LYP/6
      31+G(d,p) support this mechanism. Thus, the crystal structure together with our
      mutagenesis studies explain the molecular mechanism of POFUT1 and provide a new
      starting point for the design of functional inhibitors to this critical enzyme in
      the future.

PMID- 21966510
TI  - Substrate binding process and mechanistic functioning of type 1 11beta
      hydroxysteroid dehydrogenase from enhanced sampling methods.
AB  - In humans, type 1 11beta-hydroxysteroid dehydrogenase (11beta-HSD-1) plays a key
      role in the regulation of the glucocorticoids balance by converting the inactive
      hormone cortisone into cortisol. Numerous functional aspects of 11beta-HSD-1 have
      been understood thanks to the availability at the Worldwide Protein Data Bank of
      a number of X-ray structures of the enzyme either alone or in complex with
      inhibitors, and to several experimental data. However at present, a complete
      description of the dynamic behaviour of 11beta-HSD-1 upon substrate binding is
      missing. To this aim we firstly docked cortisone into the catalytic site of
      11beta-HSD-1 (both wild type and Y177A mutant), and then we used steered
      molecular dynamics and metadynamics to simulate its undocking. This methodology
      helped shedding light at molecular level on the complex relationship between the
      enzyme and its natural substrate. In particular, the work highlights a) the
      reason behind the functional dimerisation of 11beta-HSD-1, b) the key role of
      Y177 in the cortisone binding event, c) the fine tuning of the active site degree
      of solvation, and d) the role of the S228-P237 loop in ligand recognition.

PMID- 21966511
TI  - Angiopoietin-like 4 regulates epidermal differentiation.
AB  - The nuclear hormone receptor PPARbeta/delta is integral to efficient wound re
      epithelialization and implicated in epidermal maturation. However, the mechanism
      underlying the latter process of epidermal differentiation remains unclear. We
      showed that ligand-activated PPARbeta/delta indirectly stimulated keratinocyte
      differentiation, requiring de novo gene transcription and protein translation.
      Using organotypic skin cultures constructed from PPARbeta/delta- and angiopoietin
      like 4 (ANGPTL4)-knockdown human keratinocytes, we showed that the expression of
      ANGPTL4, a PPARbeta/delta target gene, is essential for the receptor mediated
      epidermal differentiation. The pro-differentiation effect of PPARbeta/delta
      agonist GW501516 was also abolished when keratinocytes were co-treated with
      PPARbeta/delta antagonist GSK0660 and similarly in organotypic skin culture
      incubated with blocking ANGPTL4 monoclonal antibody targeted against the C
      terminal fibrinogen-like domain. Our focused real-time PCR gene expression
      analysis comparing the skin biopsies from wildtype and ANGPTL4-knockout mice
      confirmed a consistent down-regulation of numerous genes involved in epidermal
      differentiation and proliferation in the ANGPTL4-knockout skin. We further showed
      that the deficiency of ANGPTL4 in human keratinocytes and mice skin have
      diminished expression of various protein kinase C isotypes and phosphorylated
      transcriptional factor activator protein-1, which are well-established for their
      roles in keratinocyte differentiation. Chromatin immunoprecipitation confirmed
      that ANGPTL4 stimulated the activation and binding of JUNB and c-JUN to the
      promoter region of human involucrin and transglutaminase type 1 genes,
      respectively. Taken together, we showed that PPARbeta/delta regulates epidermal
      maturation via ANGPTL4-mediated signalling pathway.

PMID- 21966512
TI  - Hepatitis E virus ORF2 protein activates the pro-apoptotic gene CHOP and anti
      apoptotic heat shock proteins.
AB  - BACKGROUND: Hepatitis E virus (HEV) is a non-enveloped plus-strand RNA virus that
      causes acute hepatitis. The capsid protein open reading frame 2 (ORF2) is known
      to induce endoplasmic reticulum stress in ORF2 expressing cells.
      METHODOLOGY/PRINCIPAL FINDINGS: In this study we found that HEV ORF2 activates
      the expression of the pro-apoptotic gene C/EBP homologous protein (CHOP). ORF2
      stimulates the CHOP promoter mainly through AARE (amino acid response elements)
      and to a minor extent the ERSE (endoplasmic reticulum stress response elements).
      Activating transcription factor 4 (ATF4) protein binds and activates the AARE
      regulatory sites of the CHOP promoter. ORF2 expression also leads to increased
      phosphorylation of eukaryotic initiation factor 2 alpha (eIF2alpha) that in turn
      initiates the translation of ATF4 mRNA. The pro-apoptotic gene CHOP is an
      important trigger to initiate endoplasmic reticulum stress induced apoptosis.
      However, the activation of CHOP by ORF2 in this study did not induce apoptosis,
      nor did BCL2-associated X protein (Bax) translocate to mitochondria. Microarray
      analysis revealed an ORF2 specific increased expression of chaperones Hsp72,
      Hsp70B', and co-chaperone Hsp40. Co-immunoprecipitation (Co-IP) and in silico
      molecular docking analysis suggests that HEV ORF2 interacts with Hsp72. In
      addition, Hsp72 shows nuclear accumulation in ORF2 expressing cells.
      CONCLUSIONS/SIGNIFICANCE: These data provide new insight into simultaneously
      occurring counter-acting effects of HEV ORF2 that may be part of a strategy to
      prevent host suicide before completion of the viral replication cycle.

PMID- 21966513
TI  - The eukaryotic-type serine/threonine protein kinase Stk is required for biofilm
      formation and virulence in Staphylococcus epidermidis.
AB  - BACKGROUND: Serine/threonine kinases are involved in gene regulation and signal
      transduction in prokaryotes and eukaryotes. Here, we investigated the role of the
      serine/threonine kinase Stk in the opportunistic pathogen Staphylococcus
      epidermidis. METHODOLOGY/PRINCIPAL FINDINGS: We constructed an isogenic stk
      mutant of a biofilm-forming clinical S. epidermidis isolate. Presence of stk was
      important for biofilm formation in vitro and virulence in a murine subcutaneous
      foreign body infection model. Furthermore, the stk mutant exhibited phenotypes
      indicating an impact of stk on metabolic pathways. Using different constructs for
      the genetic complementation of the stk mutant strain with full-length Stk or
      specific Stk domains, we determined that the Stk intracellular kinase domain is
      important for biofilm formation and regulation of purine metabolism. Site
      specific inactivation of the Stk kinase domain led to defective biofilm
      formation, in further support of the notion that the kinase activity of Stk
      regulates biofilm formation of S. epidermidis. According to immunological
      detection of the biofilm exopolysaccharide PIA and real-time PCR of the PIA
      biosynthesis genes, the impact of stk on biofilm formation is mediated, at least
      in part, by a strong influence on PIA expression. CONCLUSIONS: Our study
      identifies Stk as an important regulator of biofilm formation and virulence of S.
      epidermidis, with additional involvement in purine metabolism and the bacterial
      stress response.

PMID- 21966514
TI  - Profiling the Trypanosoma cruzi phosphoproteome.
AB  - Protein phosphorylation is a reversible post-translational modification essential
      for the regulation of several signal transduction pathways and biological
      processes in the living cell. Therefore, the identification of protein
      phosphorylation sites is crucial to understand cell signaling control at the
      molecular level. Based on mass spectrometry, recent studies have reported the
      large-scale mapping of phosphorylation sites in various eukaryotes and
      prokaryotes. However, little is known about the impact of phosphorylation in
      protozoan parasites. To in depth characterize the phosphoproteome of Trypanosoma
      cruzi, a parasite of the Kinetoplastida class, protein samples from cells at
      different phases of the metacyclogenesis--differentiation process of the
      parasites from non-infective epimastigotes to infective metacyclic
      trypomastigotes--were enriched for phosphopeptides using TiO(2) chromatography
      and analyzed on an LTQ-Orbitrap mass spectrometer. In total, 1,671 proteins were
      identified, including 753 phosphoproteins, containing a total of 2,572
      phosphorylation sites. The distribution of phosphorylated residues was 2,162
      (84.1%) on serine, 384 (14.9%) on threonine and 26 (1.0%) on tyrosine. Here, we
      also report several consensus phosphorylation sequence motifs and as some of
      these conserved groups have enriched biological functions, we can infer the
      regulation by protein kinases of this functions. To our knowledge, our
      phosphoproteome is the most comprehensive dataset identified until now for
      Kinetoplastida species. Here we also were able to extract biological information
      and infer groups of sites phosphorylated by the same protein kinase. To make our
      data accessible to the scientific community, we uploaded our study to the data
      repositories PHOSIDA, Proteome Commons and TriTrypDB enabling researchers to
      access information about the phosphorylation sites identified here.

PMID- 21966515
TI  - The de-ubiquitinylating enzyme, USP2, is associated with the circadian clockwork
      and regulates its sensitivity to light.
AB  - We have identified a novel component of the circadian clock that regulates its
      sensitivity to light at the evening light to dark transition. USP2 (Ubiquitin
      Specific Protease 2), which de-ubiquitinylates and stabilizes target proteins, is
      rhythmically expressed in multiple tissues including the SCN. We have developed a
      knockout model of USP2 and found that exposure to low irradiance light at ZT12
      increases phase delays of USP2(-/-) mice compared to wildtype. We additionally
      show that USP2b is in a complex with several clock components and regulates the
      stability and turnover of BMAL1, which in turn alters the expression of several
      CLOCK/BMAL1 controlled genes. Rhythmic expression of USP2 in the SCN and other
      tissues offers a new level of control of the clock machinery through de
      ubiqutinylation and suggests a role for USP2 during circadian adaptation to
      environmental day length changes.

PMID- 21966516
TI  - Mariprofundus ferrooxydans PV-1 the first genome of a marine Fe(II) oxidizing
      Zetaproteobacterium.
AB  - Mariprofundus ferrooxydans PV-1 has provided the first genome of the recently
      discovered Zetaproteobacteria subdivision. Genome analysis reveals a complete TCA
      cycle, the ability to fix CO(2), carbon-storage proteins and a sugar
      phosphotransferase system (PTS). The latter could facilitate the transport of
      carbohydrates across the cell membrane and possibly aid in stalk formation, a
      matrix composed of exopolymers and/or exopolysaccharides, which is used to store
      oxidized iron minerals outside the cell. Two-component signal transduction system
      genes, including histidine kinases, GGDEF domain genes, and response regulators
      containing CheY-like receivers, are abundant and widely distributed across the
      genome. Most of these are located in close proximity to genes required for cell
      division, phosphate uptake and transport, exopolymer and heavy metal secretion,
      flagellar biosynthesis and pilus assembly suggesting that these functions are
      highly regulated. Similar to many other motile, microaerophilic bacteria, genes
      encoding aerotaxis as well as antioxidant functionality (e.g., superoxide
      dismutases and peroxidases) are predicted to sense and respond to oxygen
      gradients, as would be required to maintain cellular redox balance in the
      specialized habitat where M. ferrooxydans resides. Comparative genomics with
      other Fe(II) oxidizing bacteria residing in freshwater and marine environments
      revealed similar content, synteny, and amino acid similarity of coding sequences
      potentially involved in Fe(II) oxidation, signal transduction and response
      regulation, oxygen sensation and detoxification, and heavy metal resistance. This
      study has provided novel insights into the molecular nature of
      Zetaproteobacteria.

PMID- 21966517
TI  - Construction of a xylanase A variant capable of polymerization.
AB  - The aim of our work is to furnish enzymes with polymerization ability by creating
      fusion constructs with the polymerizable protein, flagellin, the main component
      of bacterial flagellar filaments. The D3 domain of flagellin, exposed on the
      surface of flagellar filaments, is formed by the hypervariable central portion of
      the polypeptide chain. D3 is not essential for filament formation. The concept in
      this project is to replace the D3 domain with suitable monomeric enzymes without
      adversely affecting polymerization ability, and to assemble these chimeric
      flagellins into tubular nanostructures. To test the feasibility of this approach,
      xylanase A (XynA) from B. subtilis was chosen as a model enzyme for insertion
      into the central part of flagellin. With the help of genetic engineering, a
      fusion construct was created in which the D3 domain was replaced by XynA. The
      flagellin-XynA chimera exhibited catalytic activity as well as polymerization
      ability. These results demonstrate that polymerization ability can be introduced
      into various proteins, and building blocks for rationally designed assembly of
      filamentous nanostructures can be created.

PMID- 21966518
TI  - Small molecule inhibitors of the Candida albicans budded-to-hyphal transition act
      through multiple signaling pathways.
AB  - The ability of the pathogenic yeast Candida albicans to interconvert between
      budded and hyphal growth states, herein termed the budded-to-hyphal transition
      (BHT), is important for C. albicans development and virulence. The BHT is under
      the control of multiple cell signaling pathways that respond to external stimuli,
      including nutrient availability, high temperature, and pH. Previous studies
      identified 21 small molecules that could inhibit the C. albicans BHT in response
      to carbon limitation in Spider media. However, the studies herein show that the
      BHT inhibitors had varying efficacies in other hyphal-inducing media, reflecting
      their varying abilities to block signaling pathways associated with the different
      media. Chemical epistasis analyses suggest that most, but not all, of the BHT
      inhibitors were acting through either the Efg1 or Cph1 signaling pathways.
      Notably, the BHT inhibitor clozapine, a FDA-approved drug used to treat atypical
      schizophrenia by inhibiting G-protein-coupled dopamine receptors in the brain,
      and several of its functional analogs were shown to act at the level of the Gpr1
      G-protein-coupled receptor. These studies are the first step in determining the
      target and mechanism of action of these BHT inhibitors, which may have
      therapeutic anti-fungal utility in the future.

PMID- 21966519
TI  - Polarity-dependent transcranial direct current stimulation effects on central
      auditory processing.
AB  - Given the polarity dependent effects of transcranial direct current stimulation
      (tDCS) in facilitating or inhibiting neuronal processing, and tDCS effects on
      pitch perception, we tested the effects of tDCS on temporal aspects of auditory
      processing. We aimed to change baseline activity of the auditory cortex using
      tDCS as to modulate temporal aspects of auditory processing in healthy subjects
      without hearing impairment. Eleven subjects received 2mA bilateral anodal,
      cathodal and sham tDCS over auditory cortex in a randomized and counterbalanced
      order. Subjects were evaluated by the Random Gap Detection Test (RGDT), a test
      measuring temporal processing abilities in the auditory domain, before and during
      the stimulation. Statistical analysis revealed a significant interaction effect
      of time vs. tDCS condition for 4000 Hz and for clicks. Post-hoc tests showed
      significant differences according to stimulation polarity on RGDT performance:
      anodal improved 22.5% and cathodal decreased 54.5% subjects' performance, as
      compared to baseline. For clicks, anodal also increased performance in 29.4% when
      compared to baseline. tDCS presented polarity-dependent effects on the activity
      of the auditory cortex, which results in a positive or negative impact in a
      temporal resolution task performance. These results encourage further studies
      exploring tDCS in central auditory processing disorders.

PMID- 21966520
TI  - Cost-effectiveness of total hip and knee replacements for the Australian
      population with osteoarthritis: discrete-event simulation model.
AB  - BACKGROUND: Osteoarthritis constitutes a major musculoskeletal burden for the
      aged Australians. Hip and knee replacement surgeries are effective interventions
      once all conservative therapies to manage the symptoms have been exhausted. This
      study aims to evaluate the cost-effectiveness of hip and knee replacements in
      Australia. To our best knowledge, the study is the first attempt to account for
      the dual nature of hip and knee osteoarthritis in modelling the severities of
      right and left joints separately. METHODOLOGY/PRINCIPAL FINDINGS: We developed a
      discrete-event simulation model that follows up the individuals with
      osteoarthritis over their lifetimes. The model defines separate attributes for
      right and left joints and accounts for several repeat replacements. The
      Australian population with osteoarthritis who were 40 years of age or older in
      2003 were followed up until extinct. Intervention effects were modelled by means
      of disability-adjusted life-years (DALYs) averted. Both hip and knee replacements
      are highly cost effective (AUD 5,000 per DALY and AUD 12,000 per DALY
      respectively) under an AUD 50,000/DALY threshold level. The exclusion of cost
      offsets, and inclusion of future unrelated health care costs in extended years of
      life, did not change the findings that the interventions are cost-effective (AUD
      17,000 per DALY and AUD 26,000 per DALY respectively). However, there was a
      substantial difference between hip and knee replacements where surgeries
      administered for hips were more cost-effective than for knees.
      CONCLUSIONS/SIGNIFICANCE: Both hip and knee replacements are cost-effective
      interventions to improve the quality of life of people with osteoarthritis. It
      was also shown that the dual nature of hip and knee OA should be taken into
      account to provide more accurate estimation on the cost-effectiveness of hip and
      knee replacements.

PMID- 21966521
TI  - Chemokines and inflammatory mediators interact to regulate adult murine neural
      precursor cell proliferation, survival and differentiation.
AB  - Adult neural precursor cells (NPCs) respond to injury or disease of the CNS by
      migrating to the site of damage or differentiating locally to replace lost cells.
      Factors that mediate this injury induced NPC response include chemokines and pro
      inflammatory cytokines, such as tumor necrosis factor-alpha (TNFalpha) and
      interferon-gamma (IFNgamma), which we have shown previously promotes neuronal
      differentiation. RT-PCR was used to compare expression of chemokines and their
      receptors in normal adult mouse brain and in cultured NPCs in response to
      IFNgamma and TNFalpha. Basal expression of many chemokines and their receptors
      was found in adult brain, predominantly in neurogenic regions, with
      OB?SVZ>hippocampus and little or no expression in non-neurogenic regions, such as
      cortex. Treatment of SVZ-derived NPCs with IFNgamma and TNFalpha (alone and in
      combination) resulted in significant upregulation of expression of specific
      chemokines, with CXCL1, CXCL9 and CCL2 most highly upregulated and CCL19
      downregulated. Unlike IFNgamma, chemokine treatment of NPCs in vitro had little
      or no effect on survival, proliferation or migration. Neuronal differentiation
      was promoted by CXCL9, CCL2 and CCL21, while astrocyte and total oligodendrocyte
      differentiation was not affected. However, IFNgamma, CXCL1, CXCL9 and CCL2
      promoted oligodendrocyte maturation. Therefore, not only do NPCs express
      chemokine receptors, they also produce several chemokines, particularly in
      response to inflammatory mediators. This suggests that autocrine or paracrine
      production of specific chemokines by NPCs in response to inflammatory mediators
      may regulate differentiation into mature neural cell types and may alter NPC
      responsiveness to CNS injury or disease.

PMID- 21966522
TI  - Seasonality directs contrasting food collection behavior and nutrient regulation
      strategies in ants.
AB  - Long-lived animals, including social insects, often display seasonal shifts in
      foraging behavior. Foraging is ultimately a nutrient consumption exercise, but
      the effect of seasonality per se on changes in foraging behavior, particularly as
      it relates to nutrient regulation, is poorly understood. Here, we show that field
      collected fire ant colonies, returned to the laboratory and maintained under
      identical photoperiod, temperature, and humidity regimes, and presented with
      experimental foods that had different protein (p) to carbohydrate (c) ratios,
      practice summer- and fall-specific foraging behaviors with respect to protein
      carbohydrate regulation. Summer colonies increased the amount of food collected
      as the p:c ratio of their food became increasingly imbalanced, but fall colonies
      collected similar amounts of food regardless of the p:c ratio of their food.
      Choice experiments revealed that feeding was non-random, and that both fall and
      summer ants preferred carbohydrate-biased food. However, ants rarely ate all the
      food they collected, and their cached or discarded food always contained little
      carbohydrate relative to protein. From a nutrient regulation strategy, ants
      consumed most of the carbohydrate they collected, but regulated protein
      consumption to a similar level, regardless of season. We suggest that varied
      seasonal food collection behaviors and nutrient regulation strategies may be an
      adaptation that allows long-lived animals to meet current and future nutrient
      demands when nutrient-rich foods are abundant (e.g. spring and summer), and to
      conserve energy and be metabolically more efficient when nutritionally balanced
      foods are less abundant.

PMID- 21966523
TI  - Controlled adhesion and growth of long term glial and neuronal cultures on
      Parylene-C.
AB  - This paper explores the long term development of networks of glia and neurons on
      patterns of Parylene-C on a SiO(2) substrate. We harvested glia and neurons from
      the Sprague-Dawley (P1-P7) rat hippocampus and utilized an established cell
      patterning technique in order to investigate cellular migration, over the course
      of 3 weeks. This work demonstrates that uncontrolled glial mitosis gradually
      disrupts cellular patterns that are established early during culture. This effect
      is not attributed to a loss of protein from the Parylene-C surface, as nitrogen
      levels on the substrate remain stable over 3 weeks. The inclusion of the anti
      mitotic cytarabine (Ara-C) in the culture medium moderates glial division and
      thus, adequately preserves initial glial and neuronal conformity to underlying
      patterns. Neuronal apoptosis, often associated with the use of Ara-C, is
      mitigated by the addition of brain derived neurotrophic factor (BDNF). We believe
      that with the right combination of glial inhibitors and neuronal promoters, the
      Parylene-C based cell patterning method can generate structured, active neural
      networks that can be sustained and investigated over extended periods of time. To
      our knowledge this is the first report on the concurrent application of Ara-C and
      BDNF on patterned cell cultures.

PMID- 21966524
TI  - Tumor suppressor p53 functions as a negative regulator in IgE-mediated mast cell
      activation.
AB  - Mast cells are known to play a pivotal role in allergic diseases such as allergic
      rhinitis, asthma, and atopic dermatitis by releasing granules containing
      histamine, LTC4, and other preformed chemical mediators. Previous reports have
      demonstrated that IKK2 (also called IKKbeta), a central intracellular component
      of NF-kappaB activation pathways, plays a critical role in IgE-mediated
      degranulation of mast cells and anaphylaxis in mice. In this study, we show that
      protein levels of tumor suppressor p53 are up-regulated upon IgE-mediated
      activation in mast cells and lack of p53 results in enhanced responses in both
      early and late phase anaphylaxis. p53 inhibits not only the catalytic activity of
      IKK2 presumably through the modulation of glycosylation but also p65 (RelA)
      mediated transactivation. Our findings are the first to demonstrate that p53
      functions as a negative regulator in mast cells.

PMID- 21966525
TI  - Prevalence of Campylobacter species in adult Crohn's disease and the preferential
      colonization sites of Campylobacter species in the human intestine.
AB  - INTRODUCTION: Crohn's disease (CD) and ulcerative colitis (UC) are the two major
      forms of inflammatory bowel disease (IBD). A high prevalence of Campylobacter
      concisus was previously detected in paediatric CD and adult UC. Currently, the
      prevalence of C. concisus in adult CD and the preferential colonization sites of
      Campylobacter species in the human intestine are unknown. In this study, we
      examined the prevalence of Campylobacter species in biopsies collected from
      multiple anatomic sites of adult patients with IBD and controls. METHODS: Three
      hundred and one biopsies collected from ileum, caecum, descending colon and
      rectum of 28 patients IBD (15 CD and 13 UC) and 33 controls were studied.
      Biopsies were used for DNA extraction and detection of Campylobacter species by
      PCR-sequencing and Campylobacter cultivation. RESULTS: A significantly higher
      prevalence of C. concisus in colonic biopsies of patients with CD (53%) was
      detected as compared with the controls (18%). Campylobacter genus-PCR positivity
      and C. concisus positivity in patients with UC were 85% and 77% respectively,
      being significantly higher than that in the controls (48% and 36%). C. concisus
      was more often detected in descending colonic and rectal biopsies from patients
      with IBD in comparison to the controls. C. concisus was isolated from patients
      with IBD. CONCLUSION: The high intestinal prevalence of C. concisus in patients
      with IBD, particularly in the proximal large intestine, suggests that future
      studies are needed to investigate the possible involvement of C. concisus in a
      subgroup of human IBD. To our knowledge, this is the first report of the
      association between adult CD and C. concisus as well as the first study of the
      preferential colonization sites of C. concisus in the human intestine.

PMID- 21966526
TI  - Distance in motion: response trajectories reveal the dynamics of number
      comparison.
AB  - Cognitive and neuroscientific evidence has challenged the widespread view that
      perception, cognition and action constitute independent, discrete stages. For
      example, in continuous response trajectories toward a target response location,
      evidence suggests that a decision on which target to reach for (i.e., the
      cognition stage) is not reached before the movement starts (i.e., the action
      stage). As a result, instead of a straight trajectory to the correct target
      response, movement trajectories may curve toward competing responses or away from
      inhibited responses. In the present study, we examined response trajectories
      during a number comparison task. Participants had to decide whether a target
      number was smaller or larger than 5. They had to respond by moving to a left or a
      right response location. Replicating previous results, response trajectories were
      more curved toward the incorrect response location when distance to 5 was small
      (e.g., target number 4) than when distance to 5 was large (e.g., target number
      1). Importantly, we manipulated the response mapping, which allowed us to
      demonstrate that this response trajectory effect results from the relative amount
      of evidence for the available responses across time. In this way, the present
      study stresses the tight coupling of number representations (i.e., cognition) and
      response related processes (i.e., action) and shows that these stages are not
      separable in time.

PMID- 21966527
TI  - Effect of hydrogen peroxide and superoxide anions on cytosolic Ca2+: comparison
      of endothelial cells from large-sized and small-sized arteries.
AB  - We compared the Ca(2+) responses to reactive oxygen species (ROS) between mouse
      endothelial cells derived from large-sized arteries, aortas (aortic ECs), and
      small-sized arteries, mesenteric arteries (MAECs). Application of hydrogen
      peroxide (H(2)O(2)) caused an increase in cytosolic Ca(2+) levels ([Ca(2+)](i))
      in both cell types. The [Ca(2+)](i) rises diminished in the presence of U73122, a
      phospholipase C inhibitor, or Xestospongin C (XeC), an inhibitor for inositol
      1,4,5-trisphosphate (IP(3)) receptors. Removal of Ca(2+) from the bath also
      decreased the [Ca(2+)](i) rises in response to H(2)O(2). In addition, treatment
      of endothelial cells with H(2)O(2) reduced the [Ca(2+)](i) responses to
      subsequent challenge of ATP. The decreased [Ca(2+)](i) responses to ATP were
      resulted from a pre-depletion of intracellular Ca(2+) stores by H(2)O(2).
      Interestingly, we also found that Ca(2+) store depletion was more sensitive to
      H(2)O(2) treatment in endothelial cells of mesenteric arteries than those of
      aortas. Hypoxanthine-xanthine oxidase (HX-XO) was also found to induce
      [Ca(2+)](i) rises in both types of endothelial cells, the effect of which was
      mediated by superoxide anions and H(2)O(2) but not by hydroxyl radical. H(2)O(2)
      contribution in HX-XO-induced [Ca(2+)](i) rises were more significant in
      endothelial cells from mesenteric arteries than those from aortas. In summary,
      H(2)O(2) could induce store Ca(2+) release via phospholipase C-IP(3) pathway in
      endothelial cells. Resultant emptying of intracellular Ca(2+) stores contributed
      to the reduced [Ca(2+)](i) responses to subsequent ATP challenge. The [Ca(2+)](i)
      responses were more sensitive to H(2)O(2) in endothelial cells of small-sized
      arteries than those of large-sized arteries.

PMID- 21966528
TI  - Developing a highly stable PLGA-mPEG nanoparticle loaded with cisplatin for
      chemotherapy of ovarian cancer.
AB  - BACKGROUND: Cisplatin is a potent anticancer drug, but its clinical application
      has been limited due to its undesirable physicochemical characteristics and
      severe side effects. Better drug formulations for cisplatin are highly desired.
      METHODOLOGY/PRINCIPAL FINDINGS: Herein, we have developed a nanoparticle
      formulation for cisplatin with high encapsulation efficiency and reduced toxicity
      by using cisplatin-crosslinked carboxymethyl cellulose (CMC) core nanoparticles
      made from poly(lactide-co-glycolide)-monomethoxy-poly(polyethylene glycol)
      copolymers (PLGA-mPEG). The nanoparticles have an average diameter of
      approximately 80 nm measured by transmission electron microscope (TEM). The
      encapsulation efficiency of cisplatin in the nanoparticles is up to 72%.
      Meanwhile, we have also observed a controlled release of cisplatin in a sustained
      manner and dose-dependent treatment efficacy of cisplatin-loaded nanoparticles
      against IGROV1-CP cells. Moreover, the median lethal dose (LD(50)) of the
      cisplatin-loaded nanoparticles was more than 100 mg/kg by intravenous
      administration, which was much higher than that of free cisplatin. CONCLUSION:
      This developed cisplatin-loaded nanoparticle is a promising formulation for the
      delivery of cisplatin, which will be an effective therapeutic regimen of ovarian
      cancer without severe side effects and cumulative toxicity.

PMID- 21966529
TI  - Phase resetting of the mammalian circadian clock relies on a rapid shift of a
      small population of pacemaker neurons.
AB  - The circadian pacemaker of the suprachiasmatic nuclei (SCN) contains a major
      pacemaker for 24 h rhythms that is synchronized to the external light-dark cycle.
      In response to a shift in the external cycle, neurons of the SCN resynchronize
      with different pace. We performed electrical activity recordings of the SCN of
      rats in vitro following a 6 hour delay of the light-dark cycle and observed a
      bimodal electrical activity pattern with a shifted and an unshifted component.
      The shifted component was relatively narrow as compared to the unshifted
      component (2.2 h and 5.7 h, respectively). Curve fitting and simulations
      predicted that less than 30% of the neurons contribute to the shifted component
      and that their phase distribution is small. This prediction was confirmed by
      electrophysiological recordings of neuronal subpopulations. Only 25% of the
      neurons exhibited an immediate shift in the phase of the electrical activity
      rhythms, and the phases of the shifted subpopulations appeared significantly more
      synchronized as compared to the phases of the unshifted subpopulations (p<0.05).
      We also performed electrical activity recordings of the SCN following a 9 hour
      advance of the light-dark cycle. The phase advances induced a large desynchrony
      among the neurons, but consistent with the delays, only 19% of the neurons peaked
      at the mid of the new light phase. The data suggest that resetting of the central
      circadian pacemaker to both delays and advances is brought about by an initial
      shift of a relatively small group of neurons that becomes highly synchronized
      following a shift in the external cycle. The high degree of synchronization of
      the shifted neurons may add to the ability of this group to reset the pacemaker.
      The large desynchronization observed following advances may contribute to the
      relative difficulty of the circadian system to respond to advanced light cycles.

PMID- 21966530
TI  - MU2 and HP1a regulate the recognition of double strand breaks in Drosophila
      melanogaster.
AB  - Chromatin structure regulates the dynamics of the recognition and repair of DNA
      double strand breaks; open chromatin enhances the recruitment of DNA damage
      response factors, while compact chromatin is refractory to the assembly of
      radiation-induced repair foci. MU2, an orthologue of human MDC1, a scaffold for
      ionizing radiation-induced repair foci, is a widely distributed chromosomal
      protein in Drosophila melanogaster that moves to DNA repair foci after
      irradiation. Here we show using yeast 2 hybrid screens and co-immunoprecipitation
      that MU2 binds the chromoshadow domain of the heterochromatin protein HP1 in
      untreated cells. We asked what role HP1 plays in the formation of repair foci and
      cell cycle control in response to DNA damage. After irradiation repair foci form
      in heterochromatin but are shunted to the edge of heterochromatic regions an HP1
      dependent manner, suggesting compartmentalized repair. Hydroxyurea-induced repair
      foci that form at collapsed replication forks, however, remain in the
      heterochromatic compartment. HP1a depletion in irradiated imaginal disc cells
      increases apoptosis and disrupts G2/M arrest. Further, cells irradiated in
      mitosis produced more and brighter repair foci than to cells irradiated during
      interphase. Thus, the interplay between MU2 and HP1a is dynamic and may be
      different in euchromatin and heterochromatin during DNA break recognition and
      repair.

PMID- 21966531
TI  - Eukaryotic evolutionary transitions are associated with extreme codon bias in
      functionally-related proteins.
AB  - Codon bias in the genome of an organism influences its phenome by changing the
      speed and efficiency of mRNA translation and hence protein abundance. We
      hypothesized that differences in codon bias, either between-species differences
      in orthologous genes, or within-species differences between genes, may play an
      evolutionary role. To explore this hypothesis, we compared the genome-wide codon
      bias in six species that occupy vital positions in the Eukaryotic Tree of Life.
      We acquired the entire protein coding sequences for these organisms, computed the
      codon bias for all genes in each organism and explored the output for
      relationships between codon bias and protein function, both within- and between
      lineages. We discovered five notable coordinated patterns, with extreme codon
      bias most pronounced in traits considered highly characteristic of a given
      lineage. Firstly, the Homo sapiens genome had stronger codon bias for DNA-binding
      transcription factors than the Saccharomyces cerevisiae genome, whereas the
      opposite was true for ribosomal proteins--perhaps underscoring transcriptional
      regulation in the origin of complexity. Secondly, both mammalian species examined
      possessed extreme codon bias in genes relating to hair--a tissue unique to
      mammals. Thirdly, Arabidopsis thaliana showed extreme codon bias in genes
      implicated in cell wall formation and chloroplast function--which are unique to
      plants. Fourthly, Gallus gallus possessed strong codon bias in a subset of genes
      encoding mitochondrial proteins--perhaps reflecting the enhanced bioenergetic
      efficiency in birds that co-evolved with flight. And lastly, the G. gallus genome
      had extreme codon bias for the Ciliary Neurotrophic Factor--which may help to
      explain their spontaneous recovery from deafness. We propose that extreme codon
      bias in groups of genes that encode functionally related proteins has a pathway
      level energetic explanation.

PMID- 21966532
TI  - Diffusion of myosin V on microtubules: a fine-tuned interaction for which E-hooks
      are dispensable.
AB  - Organelle transport in eukaryotes employs both microtubule and actin tracks to
      deliver cargo effectively to their destinations, but the question of how the two
      systems cooperate is still largely unanswered. Recently, in vitro studies
      revealed that the actin-based processive motor myosin V also binds to, and
      diffuses along microtubules. This biophysical trick enables cells to exploit both
      tracks for the same transport process without switching motors. The detailed
      mechanisms underlying this behavior remain to be solved. By means of single
      molecule Total Internal Reflection Microscopy (TIRFM), we show here that
      electrostatic tethering between the positively charged loop 2 and the negatively
      charged C-terminal E-hooks of microtubules is dispensable. Furthermore, our data
      indicate that in addition to charge-charge interactions, other interaction forces
      such as non-ionic attraction might account for myosin V diffusion. These findings
      provide evidence for a novel way of myosin tethering to microtubules that does
      not interfere with other E-hook-dependent processes.

PMID- 21966533
TI  - Molecular characterization of transcriptional regulation of rovA by PhoP and RovA
      in Yersinia pestis.
AB  - BACKGROUND: Yersinia pestis is the causative agent of plague. The two
      transcriptional regulators, PhoP and RovA, are required for the virulence of Y.
      pestis through the regulation of various virulence-associated loci. They are the
      global regulators controlling two distinct large complexes of cellular pathways.
      METHODOLOGY/PRINCIPAL FINDINGS: Based on the LacZ fusion, primer extension, gel
      mobility shift, and DNase I footprinting assays, RovA is shown to recognize both
      of the two promoters of its gene in Y. pestis. The autoregulation of RovA appears
      to be a conserved mechanism shared by Y. pestis and its closely related
      progenitor, Y. pseudotuberculosis. In Y. pestis, the PhoP regulator responds to
      low magnesium signals and then negatively controls only one of the two promoters
      of rovA through PhoP-promoter DNA association. CONCLUSIONS/SIGNIFICANCE: RovA is
      a direct transcriptional activator for its own gene in Y. pestis, while PhoP
      recognizes the promoter region of rovA to repress its transcription. The direct
      regulatory association between PhoP and RovA bridges the PhoP and RovA regulons
      in Y. pestis.

PMID- 21966534
TI  - CYP17A1 intron mutation causing cryptic splicing in 17alpha-hydroxylase
      deficiency.
AB  - 17alpha-Hydroxylase/17, 20-lyase deficiency (17OHD) is an autosomal recessive
      disease causing congenital adrenal hyperplasia and a rare cause of hypertension
      with hypokalemia. The CYP17A1 gene mutation leads to 17OHD and its clinical
      features. We described an 18 y/o female with clinical features of 17alpha
      hydroxylase/17, 20-lyase deficiency and characterized the functional consequences
      of an intronic CYP17A1 mutation. The coding regions and flanking intronic bases
      of the CYP17A1 gene were amplified by PCR and sequenced. The patient is a
      compound heterozygote for the previously described p.R358X and IVS1 +2T>C
      mutations. A first intron splice donor site mutation was re-created in minigene
      and full-length expression vectors. Pre-mRNA splicing of the variant CYP17A1
      intron was studied in transfected cells and in a transformed lymphoblastoid cell
      line. When the full-length CYP17A1 gene and minigene containing the intronic
      mutation was expressed in transfected cells, the majority (>90%) of mRNA
      transcripts were incorrectly spliced. Only the p.R358X transcript was detected in
      the EBV-transformed lymphoblastoid cell line. The IVS1 +2T>C mutation abolished
      most 17alpha-hydroxylase/17, 20-lyase enzyme activity by aberrant mRNA splicing
      to an intronic pseudo-exon, causing a frame shift and early termination.

PMID- 21966535
TI  - The whereabouts of an ancient wanderer: global phylogeography of the solitary
      ascidian Styela plicata.
AB  - Genetic tools have greatly aided in tracing the sources and colonization history
      of introduced species. However, recurrent introductions and repeated shuffling of
      populations may have blurred some of the genetic signals left by ancient
      introductions. Styela plicata is a solitary ascidian distributed worldwide.
      Although its origin remains unclear, this species is believed to have spread
      worldwide by travelling on ship's hulls. The goals of this study were to infer
      the genetic structure and global phylogeography of S. plicata and to look for
      present-day and historical genetic patterns. Two genetic markers were used: a
      fragment of the mitochondrial gene Cytochrome Oxidase subunit I (COI) and a
      fragment of the nuclear gene Adenine Nucleotide Transporter/ADP-ATP Translocase
      (ANT). A total of 368 individuals for COI and 315 for ANT were sequenced from 17
      locations worldwide. The levels of gene diversity were moderate for COI to high
      for ANT. The Mediterranean populations showed the least diversity and allelic
      richness for both markers, while the Indian, Atlantic and Pacific Oceans had the
      highest gene and nucleotide diversities. Network and phylogenetic analyses with
      COI and ANT revealed two groups of alleles separated by 15 and 4 mutational
      steps, respectively. The existence of different lineages suggested an ancient
      population split. However, the geographic distributions of these groups did not
      show any consistent pattern, indicating different phylogeographic histories for
      each gene. Genetic divergence was significant for many population-pairs
      irrespective of the geographic distance among them. Stochastic introduction
      events are reflected in the uneven distribution of COI and ANT allele frequencies
      and groups among many populations. Our results confirmed that S. plicata has been
      present in all studied oceans for a long time, and that recurrent colonization
      events and occasional shuffling among populations have determined the actual
      genetic structure of this species.

PMID- 21966536
TI  - Leukocyte- and platelet-derived microvesicle interactions following in vitro and
      in vivo activation of toll-like receptor 4 by lipopolysaccharide.
AB  - BACKGROUND: Pro-coagulant membrane microvesicles (MV) derived from platelets and
      leukocytes are shed into the circulation following receptor-mediated activation,
      cell-cell interaction, and apoptosis. Platelets are sentinel markers of toll-like
      receptor 4 (TLR4) activation. Experiments were designed to evaluate the time
      course and mechanism of direct interactions between platelets and leukocytes
      following acute activation of TLR4 by bacterial lipopolysaccharide (LPS).
      METHODOLOGY/PRINCIPAL FINDINGS: Blood from age-matched male and female wild type
      (WT) and TLR4 gene deleted (dTLR4) mice was incubated with ultra-pure E. coli LPS
      (500 ng/ml) for up to one hour. At designated periods, leukocyte antigen positive
      platelets, platelet antigen positive leukocytes and cell-derived MV were
      quantified by flow cytometry. Numbers of platelet- or leukocyte-derived MV did
      not increase within one hour following in vitro exposure of blood to LPS.
      However, with LPS stimulation numbers of platelets staining positive for both
      platelet- and leukocyte-specific antigens increased in blood derived from WT but
      not dTLR4 mice. This effect was blocked by inhibition of TLR4 signaling mediated
      by My88 and TRIF. Seven days after a single intravenous injection of LPS (500
      ng/mouse or 20 ng/gm body wt) to WT mice, none of the platelets stained for
      leukocyte antigen. However, granulocytes, monocytes and apoptotic bodies stained
      positive for platelet antigens. CONCLUSIONS/SIGNIFICANCE: Within one hour of
      exposure to LPS, leukocytes exchange surface antigens with platelets through TLR4
      activation. In vivo, leukocyte expression of platelet antigen is retained after a
      single exposure to LPS following turn over of the platelet pool. Acute expression
      of leukocyte antigen on platelets within one hour of exposure to LPS and the
      sustained expression of platelet antigen on leukocytes following a single acute
      exposure to LPS in vivo explains, in part, associations of platelets and
      leukocytes in response to bacterial infection and changes in thrombotic
      propensity of the blood.

PMID- 21966537
TI  - A time-series method for automated measurement of changes in mitotic and
      interphase duration from time-lapse movies.
AB  - BACKGROUND: Automated time-lapse microscopy can visualize proliferation of large
      numbers of individual cells, enabling accurate measurement of the frequency of
      cell division and the duration of interphase and mitosis. However, extraction of
      quantitative information by manual inspection of time-lapse movies is too time
      consuming to be useful for analysis of large experiments. METHODOLOGY/PRINCIPAL
      FINDINGS: Here we present an automated time-series approach that can measure
      changes in the duration of mitosis and interphase in individual cells expressing
      fluorescent histone 2B. The approach requires analysis of only 2 features,
      nuclear area and average intensity. Compared to supervised learning approaches,
      this method reduces processing time and does not require generation of training
      data sets. We demonstrate that this method is as sensitive as manual analysis in
      identifying small changes in interphase or mitotic duration induced by drug or
      siRNA treatment. CONCLUSIONS/SIGNIFICANCE: This approach should facilitate
      automated analysis of high-throughput time-lapse data sets to identify small
      molecules or gene products that influence timing of cell division.

PMID- 21966538
TI  - The importance of the stem cell marker prominin-1/CD133 in the uptake of
      transferrin and in iron metabolism in human colon cancer Caco-2 cells.
AB  - As the pentaspan stem cell marker CD133 was shown to bind cholesterol and to
      localize in plasma membrane protrusions, we investigated a possible function for
      CD133 in endocytosis. Using the CD133 siRNA knockdown strategy and non
      differentiated human colon cancer Caco-2 cells that constitutively over-expressed
      CD133, we provide for the first time direct evidence for a role of CD133 in the
      intracellular accumulation of fluorescently labeled extracellular compounds.
      Assessed using AC133 monoclonal antibody, CD133 knockdown was shown to improve
      Alexa488-transferrin (Tf) uptake in Caco-2 cells but had no impact on FITC
      dextran or FITC-cholera-toxin. Absence of effect of the CD133 knockdown on Tf
      recycling established a role for CD133 in inhibiting Tf endocytosis rather than
      in stimulating Tf exocytosis. Use of previously identified inhibitors of known
      endocytic pathways and the positive impact of CD133 knockdown on cellular uptake
      of clathrin-endocytosed synthetic lipid nanocapsules supported that CD133 impact
      on endocytosis was primarily ascribed to the clathrin pathway. Also, cholesterol
      extraction with methyl-beta-cyclodextrine up regulated Tf uptake at greater
      intensity in the CD133(high) situation than in the CD133(low) situation, thus
      suggesting a role for cholesterol in the inhibitory effect of CD133 on
      endocytosis. Interestingly, cell treatment with the AC133 antibody down regulated
      Tf uptake, thus demonstrating that direct extracellular binding to CD133 could
      affect endocytosis. Moreover, flow cytometry and confocal microscopy established
      that down regulation of CD133 improved the accessibility to the TfR from the
      extracellular space, providing a mechanism by which CD133 inhibited Tf uptake. As
      Tf is involved in supplying iron to the cell, effects of iron supplementation and
      deprivation on CD133/AC133 expression were investigated. Both demonstrated a dose
      dependent down regulation here discussed to the light of transcriptional and post
      transciptional effects. Taken together, these data extend our knowledge of the
      function of CD133 and underline the interest of further exploring the CD133-Tf
      iron network.

PMID- 21966539
TI  - Group size and nest spacing affect Buggy Creek virus (Togaviridae: Alphavirus)
      infection in nestling house sparrows.
AB  - The transmission of parasites and pathogens among vertebrates often depends on
      host population size, host species diversity, and the extent of crowding among
      potential hosts, but little is known about how these variables apply to most
      vector-borne pathogens such as the arboviruses (arthropod-borne viruses). Buggy
      Creek virus (BCRV; Togaviridae: Alphavirus) is an RNA arbovirus transmitted by
      the swallow bug (Oeciacus vicarius) to the cliff swallow (Petrochelidon
      pyrrhonota) and the introduced house sparrow (Passer domesticus) that has
      recently invaded swallow nesting colonies. The virus has little impact on cliff
      swallows, but house sparrows are seriously affected by BCRV. For house sparrows
      occupying swallow nesting colonies in western Nebraska, USA, the prevalence of
      BCRV in nestling sparrows increased with sparrow colony size at a site but
      decreased with the number of cliff swallows present. If one nestling in a nest
      was infected with the virus, there was a greater likelihood that one or more of
      its nest-mates would also be infected than nestlings chosen at random. The closer
      a nest was to another nest containing infected nestlings, the greater the
      likelihood that some of the nestlings in the focal nest would be BCRV-positive.
      These results illustrate that BCRV represents a cost of coloniality for a
      vertebrate host (the house sparrow), perhaps the first such demonstration for an
      arbovirus, and that virus infection is spatially clustered within nests and
      within colonies. The decreased incidence of BCRV in sparrows as cliff swallows at
      a site increased reflects the "dilution effect," in which virus transmission is
      reduced when a vector switches to feeding on a less competent vertebrate host.

PMID- 21966540
TI  - Dopamine receptors in human adipocytes: expression and functions.
AB  - INTRODUCTION: Dopamine (DA) binds to five receptors (DAR), classified by their
      ability to increase (D1R-like) or decrease (D2R-like) cAMP. In humans, most DA
      circulates as dopamine sulfate (DA-S), which can be de-conjugated to bioactive DA
      by arylsulfatase A (ARSA). The objective was to examine expression of DAR and
      ARSA in human adipose tissue and determine whether DA regulates prolactin (PRL)
      and adipokine expression and release. METHODS: DAR were analyzed by RT-PCR and
      Western blotting in explants, primary adipocytes and two human adipocyte cell
      lines, LS14 and SW872. ARSA expression and activity were determined by qPCR and
      enzymatic assay. PRL expression and release were determined by luciferase
      reporter and Nb2 bioassay. Analysis of cAMP, cGMP, leptin, adiponectin and
      interleukin 6 (IL-6) was done by ELISA. Activation of MAPK and PI3 kinase/Akt was
      determined by Western blotting. RESULTS: DAR are variably expressed at the mRNA
      and protein levels in adipose tissue and adipocytes during adipogenesis. ARSA
      activity in adipocyte increases after differentiation. DA at nM concentrations
      suppresses cAMP, stimulates cGMP, and activates MAPK in adipocytes. Acting via
      D2R-like receptors, DA and DA-S inhibit PRL gene expression and release. Acting
      via D1R/D5R receptors, DA suppresses leptin and stimulates adiponectin and IL-6
      release. CONCLUSIONS: This is the first report that human adipocytes express
      functional DAR and ARSA, suggesting a regulatory role for peripheral DA in
      adipose functions. We speculate that the propensity of some DAR-activating
      antipsychotics to increase weight and alter metabolic homeostasis is due, in
      part, to their direct action on adipose tissue.

PMID- 21966542
TI  - Nuclear-targeted deleted in liver cancer 1 (DLC1) is less efficient in exerting
      its tumor suppressive activity both in vitro and in vivo.
AB  - BACKGROUND: Deleted in liver cancer 1 (DLC1) serves as an important RhoGTPase
      activating protein (RhoGAP) protein that terminates active RhoA signaling in
      human cancers. Increasing evidence has demonstrated that the tumor suppressive
      activity of DLC1 depends not only on RhoGAP activity, but also relies on proper
      focal adhesion localization through its interaction with tensin family proteins.
      Recently, there are reports showing that DLC1 can also be found in the nucleus;
      however, the existence and the relative tumor suppressive activity of nuclear
      DLC1 have never been clearly addressed. METHODOLOGY AND PRINCIPAL FINDINGS: We
      herein provide new evidence that DLC1 protein, which predominantly associated
      with focal adhesions and localized in cytosol, dynamically shuttled between
      cytoplasm and nucleus. Treatment of cells with nuclear export blocker, Leptomycin
      B (LMB), retained DLC1 in the nucleus. To understand the nuclear entry of DLC1,
      we identified amino acids 600-700 of DLC1 as a novel region that is important for
      its nuclear localization. The tumor suppressive activity of nuclear DLC1 was
      directly assessed by employing a nuclear localization signal (NLS) fusion variant
      of DLC1 (NLS-DLC1) with preferential nuclear localization. In SMMC-7721 HCC
      cells, expression of NLS-DLC1 failed to suppress colony formation and actin
      stress fiber formation in vitro. The abrogated tumor suppressive activity of
      nuclear DLC1 was demonstrated for the first time in vivo by subcutaneously
      injecting p53(-/-) RasV12 hepatoblasts with stable NLS-DLC1 expression in nude
      mice. The injected hepatoblasts with NLS-DLC1 expression effectively formed
      tumors when compared with the non-nuclear targeted DLC1.
      CONCLUSIONS/SIGNIFICANCE: Our study identified a novel region responsible for the
      nuclear entry of DLC1 and demonstrated the functional difference of DLC1 in
      different cellular compartments both in vitro and in vivo.

PMID- 21966541
TI  - Basal LAT-diacylglycerol-RasGRP1 signals in T cells maintain TCRalpha gene
      expression.
AB  - In contrast to the well-characterized T cell receptor (TCR) signaling pathways
      that induce genes that drive T cell development or polarization of naive CD4 T
      cells into the diverse T(H)1, T(H)2, T(H)17 and T(reg) lineages, it is unclear
      what signals maintain specific gene expression in mature resting T cells. Resting
      T cells residing in peripheral lymphoid organs exhibit low-level constitutive
      signaling. Whereas tonic signals in B cells are known to be critical for
      survival, the roles of tonic signals in peripheral T cells are unknown. Here we
      demonstrate that constitutive signals in Jurkat T cell lines are transduced via
      the adapter molecule LAT and the Ras exchange factor RasGRP1 to maintain
      expression of TCRalpha mRNA and surface expression of the TCR/CD3 complex.
      Independent approaches of reducing basal activity through the LAT-diacylglycerol
      RasGRP pathway led to reduced constitutive Ras-MEK-ERK signals and decreased
      TCRalpha mRNA and surface TCR expression in Jurkat cells. However, loss of TCR
      expression takes several days in these cell line experiments. In agreement with
      these in vitro approaches, inducible deletion of Lat in vivo results in reduced
      TCRalpha mRNA- and surface TCR-expression in a delayed temporal manner as well.
      Lastly, we demonstrate that loss of basal LAT-RasGRP signals appears to lead to
      silencing or repression of TCRalpha transcription. We postulate that basal LAT
      diacylglycerol-RasGRP signals fulfill a regulatory function in peripheral T
      lymphocytes by maintaining proper gene expression programs.

PMID- 21966543
TI  - What can ecology teach us about cancer?
AB  - In 2008, Pienta et al. (Transl Oncol. 2008;1:158-164) introduced the term
      ecological therapy for cancer treatment and, in particular, emphasized that
      destruction of the tumor microenvironment would be more effective than just
      killing the cells that inhabit it. Proposed here is an expansion on the idea of
      ecological therapy of cancer, incorporating 1) literature on species invasion,
      i.e., a right cancerous clone needs to be at the right place at the right time to
      actually invade its environment, and 2) the literature on niche construction,
      that is, the idea that once a tumor is formed, cancer cells they modify their
      microenvironment (niche construction) by changing pH through glycolysis,
      secreting growth factors and recruiting tumor-associated macrophages to promote
      cell growth, activating fibroblasts, evading predation from immune system, making
      the cancer that much more difficult to eradicate. Paleontological literature
      suggests that the largestmass extinctions occurred when environmental stress that
      would weaken the population was coupled with some pulse destructive event that
      caused extensive mortality. To have the same effect on cells in the tumor, rather
      than, or at least in addition to, killing the cells, one would also need to
      target the niche that they created for themselves.

PMID- 21966545
TI  - Role of alpha(5)beta(1) Integrin Up-regulation in Radiation-Induced Invasion by
      Human Pancreatic Cancer Cells.
AB  - RADIOTHERAPY IS USED IN THE MANAGEMENT OF PANCREATIC CANCER BECAUSE OF ITS HIGH
      PROPENSITY FOR LOCOREGIONAL RELAPSE: one third of patients succumb to localized
      disease. Thus, strategies to improve the efficacy of radiotherapy in pancreatic
      cancer are important to pursue. We used naturally serum-free, selectively
      permeable basement membranes and confocal microscopy of fluorescent antibody
      stained human Panc-1, MiaPaCa-2, and BxPC-3 pancreatic cancer cell lines to
      investigate the effects of ionizing radiation on alpha(5)beta(1) integrin
      fibronectin receptor expression and on alpha(5)beta(1)-mediated invasion. We
      report that radiation rapidly induces pancreatic cancer cell invasion, and that
      radiation-induced invasion is caused by up-regulation of alpha(5)beta(1) integrin
      fibronectin receptors by transcriptional and/or postendocytic recycling
      mechanisms. We also report that radiation causes alpha(5)beta(1) up-regulation in
      Panc-1, MiaPaCa-2, and BxPC-3 tumor xenografts and that upregulated
      alpha(5)beta(1) colocalizes with upregulated early or late endosomes in Panc-1 or
      BxPC-3 tumors, respectively, although it may colocalize significantly with both
      endosome types in MiaPaCa-2 tumors. Our results suggest that systemic inhibition
      of alpha(5)beta(1)-mediated invasion might be an effective way to reduce
      radiation-induced pancreatic cancer cell invasion, thereby improving the efficacy
      of radiotherapy.

PMID- 21966547
TI  - Expression profiling of vulvar carcinoma: clues for deranged extracellular matrix
      remodeling and effects on multiple signaling pathways combined with discrete
      patient subsets.
AB  - The molecular mechanisms of vulvar squamous cell carcinoma (VSCC) remain obscure.
      To this end, we investigated systematically for the first time the expression
      profile of VSCC using the microarray technology, in a total of 11 snap-frozen
      samples, from five VSCC patients covering early and advanced stages of VSCC
      undergoing radical surgery and from six matched healthy controls. All experiments
      were performed using Affymetrix Human Genome U133A 2.0 oligonucleotide arrays,
      covering 22,277 probe sets. Genes were filtered and analyzed using analysis of
      variance, t test, fold-change calculations, and unsupervised hierarchical cluster
      analysis. Further processing included functional analysis and overrepresentation
      calculations based on Gene Ontology, Database for Annotation, Visualization, and
      Integrated Discovery, and Ingenuity Pathway Analysis. The molecular phenotypes of
      VSCC patients exhibited significant and discrete transcriptional differences from
      the healthy controls, whereas principal component analysis documented that this
      separation is mediated by a consistent set of gene expression differences. We
      detected 1077 genes (306 upregulated and 771 downregulated) that were
      differentially expressed between VSCC patients and healthy controls by at least
      twofold (P < .01), whereas a novel subset of patients was revealed displaying a
      distinct pattern of 125 upregulated genes involved in multiple cellular
      processes. Functional analysis of the 1077 genes documented their involvement in
      more than 50 signaling pathways, such as PTEN, oncostatin M, and extracellular
      signal-regulated kinase signaling, affecting extracellular matrix remodeling and
      invasion. Comparison of our data set with those of the single VIN study revealed
      that the two entities share a limited number of genes and display unique
      features.

PMID- 21966544
TI  - Animal models in carotenoids research and lung cancer prevention.
AB  - Numerous epidemiological studies have consistently demonstrated that individuals
      who eat more fruits and vegetables (which are rich in carotenoids) and who have
      higher serum beta-carotene levels have a lower risk of cancer, especially lung
      cancer. However, two human intervention trials conducted in Finland and in the
      United States have reported contrasting results with high doses of beta-carotene
      supplementation increasing the risk of lung cancer among smokers. The failure of
      these trials to demonstrate actual efficacy has resulted in the initiation of
      animal studies to reproduce the findings of these two studies and to elucidate
      the mechanisms responsible for the harmful or protective effects of carotenoids
      in lung carcinogenesis. Although these studies have been limited by a lack of
      animal models that appropriately represent human lung cancer induced by cigarette
      smoke, ferrets and A/J mice are currently the most widely used models for these
      types of studies. There are several proposed mechanisms for the protective
      effects of carotenoids on cigarette smoke-induced lung carcinogenesis, and these
      include antioxidant/prooxidant effects, modulation of retinoic acid signaling
      pathway and metabolism, induction of cytochrome P450, and molecular signaling
      involved in cell proliferation and/or apoptosis. The technical challenges
      associated with animal models include strain-specific and diet-specific effects,
      differences in the absorption and distribution of carotenoids, and differences in
      the interactions of carotenoids with other antioxidants. Despite the problems
      associated with extrapolating from animal models to humans, the understanding and
      development of various animal models may provide useful information regarding the
      protective effects of carotenoids against lung carcinogenesis.

PMID- 21966546
TI  - Simultaneous Inhibition of Estrogen Receptor and the HER2 Pathway in Breast
      Cancer: Effects of HER2 Abundance.
AB  - The estrogen receptor (ER) pathway and the epidermal growth factor receptor
      (EGFR) pathway play pivotal roles in breast cancer progression. Targeted
      therapies able to intercept ER or signaling downstream to EGFR and its kin, HER2,
      are routinely used to treat distinct groups of breast cancer patients. However,
      patient responses are limited by resistance to endocrine therapy, which may be
      due to compensatory HER2/EGFR signaling. This raises the possibility that
      simultaneous interception of HER2 and ER may enhance therapeutic efficacy. To
      address the question, we treated breast cancer cells with both fulvestrant (ICI
      182780), an ER antagonist with no agonist effects, and lapatinib, an orally
      available tyrosine kinase inhibitor specific to EGFR and HER2. Our results
      indicate that the combination of drugs is especially effective when applied to
      HER2-overexpressing, ER-positive cancer cells. Interestingly, fulvestrant
      activated the mitogen-activated protein kinase (MAPK) pathway of these cells, but
      complete inhibition of MAPK signaling was observed on cotreatment with lapatinib.
      Taken together, our observations reinforce the possibility that the effectiveness
      of combining anti-ER and anti-HER2/EGFR drugs may be especially effective on a
      relatively small subtype of HER2-overexpressing, ER-positive tumors of the
      breast.

PMID- 21966548
TI  - Immunohistochemical staining of slit2 in primary and metastatic prostatic
      adenocarcinoma.
AB  - BACKGROUND: Conflicting roles for Slit2, a protein involved in mediating the
      processes of cell migration and chemotactic response, have been previously
      described in prostate cancer. Here we use immunohistochemistry to evaluate the
      expression of Slit2 in normal donor prostate (NDP), benign prostatic hyperplasia
      (BPH), high-grade prostatic intraepithelial neoplasia (HGPIN), normal tissue
      adjacent to prostatic adenocarcinoma (NAC), primary prostatic adenocarcinoma
      (PCa), and metastatic prostatic adenocarcinoma (Mets). METHODS: Tissue
      microarrays were immunostained for Slit2. The staining intensities were
      quantified using automated image analysis software. The data was statistically
      analyzed using one-way analysis of variance with subsequent Tukey tests for
      multiple comparisons or a nonparametric equivalent. Eleven cases of NDP, 35 cases
      of NAC, 15 cases of BPH, 35 cases of HGPIN, 106 cases of PCa, and 37 cases of
      Mets were analyzed. RESULTS: Specimens of PCa and HGPIN had the highest absolute
      staining for Slit2. Significant differences were seen between PCa and NDP (P <
      .05), PCa and NAC (P < .05), HGPIN and NDP (P < .05), and HGPIN and NAC (P <
      .05). Whereas the average Mets staining was not significantly different from NDP
      or NAC, several individual Mets cases featured intense staining. CONCLUSIONS: To
      our knowledge, this represents the first study comparing the immunohistochemical
      profiles of Slit2 in PCa and Mets to specimens of HGPIN, BPH, NDP, and NAC. These
      findings suggest that Slit2 expression can be increased in HGPIN, PCa, and Mets,
      making it a potentially important biomarker for prostate cancer.

PMID- 21966549
TI  - Embryo protection in contemporary immunology: Why bacteria matter.
AB  - Early embryos of many vertebrates and invertebrates develop outside the mother
      and are exposed to a myriad of potential microbial colonizers. Here we discuss
      how these embryos are protected from microbial attacks and how they might control
      and shape their microbiota. In essence we delineate a new role for antimicrobial
      peptides both in selecting particular bacterial partners during early development
      and in being important components of a "be prepared" strategy providing
      transgenerational protection.

PMID- 21966550
TI  - A new model for caste development in social wasps.
AB  - Specialization into reproductive and non-reproductive castes is one of the
      defining traits of eusocial insects. Knowledge of the proximal causes of caste
      differentiation is therefore central to achieving an understanding of the
      evolution of eusociality. Castes are an example of a polyphenism, multiple,
      discrete phenotypes arising from a single genotype in response to differing
      environmental conditions. Here we focus on recent work in the social wasps to
      provide insight into how environmental conditions may trigger the development of
      caste across a range from independent- to swarm-founding social species. The
      amount of food larvae receive has long been recognized as a key input factor in
      the determination of caste, but that alone is insufficient to account for the
      range of combinations of size, development time and caste among the female
      offspring of Polistes, an independent-founding wasp. Recent experimental work on
      P. fuscatus has shown that vibrations that are associated with the feeding of
      larvae are another essential environmental input in the determination of caste.
      we present a model of how vibrational signaling in the context of feeding larvae
      could interact with nutritional input to account for the developmental patterns
      seen in these wasps. Mapping the distribution of vibrational signaling onto a
      phylogeny of the social wasps suggests that this trait characterized the common
      ancestor of the subfamilies vespinae + Polistinae, diversified in the independent
      founding species, then was superseded by caste-determining mechanisms in the
      swarm-founding and vespine species that function more effectively in larger
      colonies.

PMID- 21966551
TI  - Thalamic influences on multisensory integration.
AB  - In everyday life our brain often receives information about events and objects in
      the real world via several sensory modalities, because natural objects often
      stimulate more than one sense. These different types of information are processed
      in our brain along different sensory-specific pathways, but are finally
      integrated into a unified percept. During the last years, studies provided
      compelling evidence that the neural basis of multisensory integration is not
      restricted to higher association areas of the cortex, but can already occur at
      low-level stages of sensory cortical processing and even in subcortical
      structures. In this article we will review the potential role of several thalamic
      structures in multisensory interplay and discuss their extensive anatomical
      connections with sensory-specific and multisensory cortical structures. We
      conclude that sensory-specific thalamic structures may act as a crucial
      processing node of multisensory interplay in addition to their traditional role
      as sensory relaying structure.

PMID- 21966552
TI  - Resveratrol inhibits mTOR signaling by targeting DEPTOR.
AB  - Resveratrol (RSV, trans-3,4,5-Trihydroxystilbene), a type of polyphenol
      originally found in red wines, shows a great promise for the treatment of cancer,
      aging, type 2 diabetes and cardiovascular diseases. Recent studies suggest that
      suppressing the signaling pathway mediated by mTOR, a well-known energy sensor
      that integrates various hormonal, nutrient and environmental signals to regulate
      cell growth, metabolism and survival, could play an important role in mediating
      the beneficial effect of RSV. The underlying mechanisms by which RSV inhibits
      mTOR signaling remain elusive, but our recent studies show that RSV inhibits
      amino acid-stimulated mTOR signaling in C2C12 fibroblasts via a Sirt1- and AMPK
      independent mechanism. RSV treatment has no effect on the expression levels of
      mTOR, raptor and DEPTOR, but greatly promotes the interaction between mTOR and
      its inhibitor DEPTOR. Our results reveal a novel mechanism by which RSV inhibits
      mTOR signaling and its function.

PMID- 21966553
TI  - Genetically encoded force sensors for measuring mechanical forces in proteins.
AB  - THERE ARE THREE SOURCES OF FREE ENERGY FOR CELLS: chemical potential, electrical
      potential and mechanical potential. There is little known about the last one
      since there have not been simple ways to measure stress in proteins in cells. we
      have now developed genetically encoded force sensors to assess the stress in
      fibrous proteins in living cells. These FReT based fluorescence sensors can be
      read out at video rates and provide real time maps of the stress distribution in
      cells, tissues and animals. The sensors can be inserted into specific proteins
      and in general do not disturb the normal function or anatomy. The original
      sensors used mutant GFPs linked by elastic linkers. These sensors provide a
      linear output with applied stress but the response is linear in strain. To
      improve contrast and dynamic range we have now developed a new class of sensors
      that are smaller making them less invasive, and have much higher intrinsic
      sensitivity since force modulates the angle between the donor and acceptor much
      more than the distance between them. Known as cpstFRET, the probe shows improved
      biocompatibility, wider dynamic range and higher sensitivity.

PMID- 21966554
TI  - Facilitating axon regeneration in the injured CNS by microtubules stabilization.
AB  - Traumatic CNS injuries often cause permanent, devastating disabilities due to a
      lack of regeneration of damaged axons. Next to an insufficient intrinsic
      capability of CNS neurons to regrow axons, also inhibitory molecules that are
      associated with the CNS myelin and the glial scar contribute to the failure of
      axonal regeneration. Strategies targeting the inhibitory molecules, their
      receptors or downstream signaling pathways result in little improvement of
      regeneration in vivo. However, the combination of such approaches together with
      measures that increase the intrinsic growth potential of neurons reportedly lead
      to a significantly better outcome. In this mini-review we outline and discuss a
      novel therapeutic strategy facilitating axon regeneration by directly targeting
      microtubule dynamics in axonal growth cones and reducing the inhibitory scar
      formation at the injury site by the anticancer drug Taxol. Moreover, we portray
      the mechanisms underlying the beneficial effects of Taxol and its potential as an
      adjuvant drug to accomplish substantial regeneration and functional recovery
      after CNS injuries in vivo.

PMID- 21966555
TI  - ERK, synaptic plasticity and acid-induced muscle pain.
AB  - Chronic pain is characterized by post-injury pain hypersensitivity. Current
      evidence suggests that it might result from altered neuronal excitability and/or
      synaptic functions in pain-related pathways and brain areas, an effect known as
      central sensitization. Increased activity of extracellular signal-regulated
      kinase (ERK) has been well-demonstrated in the dorsal horn of the spinal cord in
      chronic pain animal models. Recently, increased ERK activity has also been
      identified in two supraspinal areas, the central amygdala and the paraventricular
      thalamic nucleus anterior. Our recent work on the capsular central amygdala has
      shown that this increased ERK activity can enhance synaptic transmission, which
      might account for central sensitization and behavior hypersensitivity in animals
      receiving noxious stimuli.

PMID- 21966557
TI  - Aurora A kinase activity is required for localization of TACC3/ch-TOG/clathrin
      inter-microtubule bridges.
AB  - Accurate chromosome segregation during mitosis is achieved by the kinetochore
      fibers (K-fibers) of the spindle apparatus. These fibers are bundles of
      microtubules (MTs) connected by non-motor bridges. We recently identified a
      TACC3/ch-TOG/clathrin complex that constitutes the shortest class of inter-MT
      bridge in K-fibers. TACC3 anchors the complex to MTs and this is dependent on
      phosphorylation by Aurora A kinase. Here we show that inhibition of Aurora A
      kinase using MLN8237 results in (1) loss of clathrin and TACC3 from spindles, (2)
      destabilization of K-fibers and (3) loss of inter-MT bridges. These results are
      similar to those in cells depleted of clathrin or TACC3; suggesting that TACC3/ch
      TOG/clathrin bridges are the major class of bridge that is regulated by this
      kinase.

PMID- 21966558
TI  - Modeling F-actin cortex influence on the secretory properties of neuroendocrine
      cells.
AB  - Chromaffin cells are considered as one of the most valuable models to study
      regulated exocytosis. In these cells, like in other neuroendocrine systems, an
      intricate cortical cytoskeleton acts as a retentive network impeding vesicle
      access to plasma membrane. Therefore, during stimulation this structure suffers a
      transient reorganization allowing active transport of vesicles toward secretory
      sites. Interestingly, a combination of confocal microscopy studies and
      mathematical modeling is showing us new aspects of the influence of cortical
      cytoskeleton in shaping the secretory properties of excitable cells. In this new
      vision the F-actin-myosin II cortical cytoskeleton is organized forming polygonal
      cages with the molecular machinery of exocytosis composed by SNARE proteins and
      voltage-dependent calcium channels associating with its border. In this way the
      cytoskeleton not only holds together the essential elements acting during
      secretion, but we proposed that could also act as a structural factor opposing to
      the free diffusion of the calcium signal and therefore sustains high levels of
      the intracellular signal triggering exocytosis.

PMID- 21966559
TI  - Inhibition of the inflammasome response by a viral protein that interacts with
      NLRs.
AB  - Pattern recognition receptors (PRRs) constitute the first line of host defense
      against bacterial, fungal and viral pathogens. Upon sensing microbial infection,
      PRRs initiate a cascade of signal transduction and transcriptional events to
      induce the production of inflammatory cytokines. As a result, many pathogens have
      evolved to evade PRR detection and activation in order to establish a successful
      infection. In a recent report, we described how a viral protein named Orf63
      encoded by Kaposi's sarcoma-associated herpesvirus (KSHV) inhibits activation of
      several members of a family of PRRs called NLRs (nucleotide-binding and
      oligomerization, leucine-rich repeat) by functionally inhibiting the NLR
      response. This resulted in reduced NLR-dependent pro-inflammatory cytokine
      secretion and cell death. Moreover, Orf63 was essential in the KSHV lifecycle.
      Thus, our work suggests KSHV has evolved to encode a functional homolog of NLR
      proteins in an effort to suppress the host inflammatory response.

PMID- 21966556
TI  - Viral infection: Moving through complex and dynamic cell-membrane structures.
AB  - Viruses have developed different survival strategies in host cells by crossing
      cell-membrane compartments, during different steps of their viral life cycle. In
      fact, the non-regenerative viral membrane of enveloped viruses needs to encounter
      the dynamic cell-host membrane, during early steps of the infection process, in
      which both membranes fuse, either at cell-surface or in an endocytic compartment,
      to promote viral entry and infection. Once inside the cell, many viruses
      accomplish their replication process through exploiting or modulating membrane
      traffic, and generating specialized compartments to assure viral replication,
      viral budding and spreading, which also serve to evade the immune responses
      against the pathogen. In this review, we have attempted to present some data that
      highlight the importance of membrane dynamics during viral entry and replicative
      processes, in order to understand how viruses use and move through different
      complex and dynamic cell-membrane structures and how they use them to persist.

PMID- 21966560
TI  - Mangrove bacterial richness.
AB  - Mangroves are complex and dynamic ecosystems varying in salinity, water level and
      nutrient availability; they also contain diverse and distinct microbial
      communities. Studies of microbes and their interactions with other ecosystem
      components (e.g., tree roots) are critical for our understanding of mangrove
      ecosystem functioning and remediation. Using a barcoding pyrosequencing approach,
      we previously noted the persistence of terrestrial bacterial populations on
      mangrove roots when nursery raised saplings were transplanted back to their
      natural environment. Here we go into further detail about the potential
      functional associations of bacterial guilds with distinct mangrove microhabitats
      including the rhizosphere. We also use a nonparametric richness estimator to show
      that estimated operational taxonomic unit (OTU) richness is more than twice that
      observed. In the transplant microhabitat, our estimate suggests that there are
      almost 7,000 OTU's for a sample size of 10,400 individual sequences with no sign
      of an asymptote, indicating that "true" richness for this microhabitat is
      substantially larger. Results on the number of bacterial OTU's should, however,
      be viewed with caution given that the barcoding pyrosequencing technique used can
      yield sequencing artifacts that may inflate richness estimates if not properly
      removed.

PMID- 21966561
TI  - Evolution of cyanobacterial morphotypes: Taxa required for improved phylogenomic
      approaches.
AB  - Within prokaryotes cyanobacteria represent one of the oldest and morphologically
      most diverse phyla on Earth. The rise of oxygen levels in the atmosphere 2.32
      2.45 billion years ago is assigned to the photosynthetic activity of ancestors
      from this phylum. Subsequently cyanobacteria were able to adapt to various
      habitats evolving a comprehensive set of different morphotypes. In a recent study
      we showed that this evolution is not a gradual transition from simple unicellular
      to more complex multicellular forms as often assumed. Instead complexity was lost
      several times and regained at least once. An understanding of the genetic basis
      of these transitions would be further strengthened by phylogenomic approaches.
      However, considering that new methods for phylogenomic analyses are emerging, it
      is unfortunate that genomes available today are comprised of an unbalanced
      sampling of taxa. We propose avenues to remedy this by identifying taxa that
      would improve the representation of phylogenetic diversity in this phylum.

PMID- 21966563
TI  - A new job for ancient extracellular matrix proteins: Hemicentins stabilize
      cleavage furrows.
AB  - Interactions between extracellular matrix (ECM) proteins and transmembrane
      receptors mediate changes in cell shape during cell migration, adhesion,
      differentiation and polarization. Cytokinesis is the final step in cell division
      as cells employ a contractile ring composed of actin and myosin to partition one
      cell into two. During the partition process, an invagination in nascent membrane
      forms a new extracellular space called the cleavage furrow. Despite the dramatic
      changes in cell shape during cytokinesis, existing models include no role for the
      ECM. In a recent paper, we show that hemicentins assemble in the cleavage furrow
      of C. elegans germ cells and mouse embryo blastomeres. Hemicentin depletion
      results in membrane destabilization, cleavage furrow retraction and cytokinesis
      failure. The data suggest that hemicentins and other ECM proteins stabilize the
      cleavage furrow during cytokinesis of multiple cell types.

PMID- 21966562
TI  - Involvement of ubiquilin-1 transcript variants in protein degradation and
      accumulation.
AB  - Controlled management of protein levels and quality is essential for normal
      cellular function. Specific molecular chaperones and foldases monitor the levels
      and assist correct folding of proteins. The ubiquitin-proteasome system
      recognizes and degrades misfolded proteins that can otherwise be harmful to
      cells. However, when misfolded or aggregated proteins excessively accumulate,
      they may be sequestered to the microtubule-organizing center to form aggresomes.
      These may then be removed from cells by autophagocytosis. Abnormal protein
      accumulation and aggregation is a common hallmark of many neurodegenerative
      diseases. In a recent study, we provide evidence that specific transcript
      variants (TVs) of ubiquilin-1, which are genetically and functionally associated
      to Alzheimer's disease (AD), regulate proteasomal and aggresomal targeting of
      presenilin-1 (PS1), a key player in AD pathogenesis. Our study together with
      current data provide interesting implications for ubiquilin-1 and its TVs in the
      pathogenesis of AD and other neurodegenerative diseases involving abnormal
      protein aggregation.

PMID- 21966564
TI  - Filopodia: Nanodevices that sense nanotopographic ECM cues to orient neurite
      outgrowth.
AB  - The processes of neuronal outgrowth and guidance have typically been studied in
      classic 2D cell culture systems that do not recapitulate topographical cues
      present in the in vivo extracellular matrix (ECM). Using microfabrication
      techniques, we mimicked this ECM topography by presenting laminin on a line
      pattern with nanometric size features. We found that this not only allows neurite
      orientation but also robust outgrowth. This depends on dynamic stochastic sensing
      of the line pattern by growth cone filopodia which allows them to probe their
      surrounding space by measuring the extent of filopodial adhesion surface with the
      ECM. Filopodium alignment with an ECM line allows to the formation of a robust F
      actin network that leads to its stabilization, allowing steady neurite extension
      along the line pattern. Because this model system allows exquisitely stereotypic
      filopodial dynamics, this opens up the possibility to easily study the spatio
      temporal dynamics of the signaling networks that regulate this prototypic growth
      cone navigation system.

PMID- 21966565
TI  - Expression of individual mammalian Sun1 isoforms depends on the cell type.
AB  - Mammalian Sun1 belongs to an evolutionarily conserved family of inner nuclear
      membrane proteins, which are known as SUN domain proteins. SUN domain proteins
      interact with KASH domain partners to form bridging complexes, so-called LINC
      complexes, that physically connect the nuclear interior to the cytoskeleton. LINC
      complexes are critical for nuclear integrity and play fundamental roles in
      nuclear positioning, shaping and movement. The mammalian genome codes for at
      least five different SUN domain proteins used for the formation of a number of
      different LINC complexes. Recently, we reported on the identification of several
      Sun1 isoforms, which tremendously enlarges the alternatives to form functional
      LINC complexes. We now confirmed that Sun1 actually exists in at least seven
      distinct splice variants. Besides that, we observed that expression of individual
      Sun1 isoforms remarkably depends on the cell type, suggesting a cell type
      specific adaption of Sun1 dependent LINC complexes to specific cellular and
      physiological requirements.

PMID- 21966566
TI  - What are the origins and phylogeny of plant hemoglobins?
AB  - Land plants and algae are now represented by about 40 genomes. Although most are
      incomplete, putative globins appear to be present in all the ca. 30 land plant
      genomes and in all except one algal genomes. The globins have either the
      canonical 3/3 alpha-helical fold characteristic of vertebrate myoglobin (Mb) or
      2/2 alpha-helical folds, characteristic of bacterial globins with a truncated Mb
      fold. In view of the fairly complete picture of the globin superfamily that is
      now available from analyses of over 1,000 bacterial genomes and >200 other
      eukaryote genomes, it is now possible to seek answers to the following twin
      questions: what is the phylogenetic relationship of plant and algal globins to
      those of other eukaryotes and what is their likely bacterial origin? We summarize
      below the available results. Molecular phylogenetic analyses indicate that plant
      and algal 3/3 globins are related to bacterial flavohemoglobins and vertebrate
      neuroglobins. Furthermore, they also suggest that plant and algal 3/3 and group 1
      2/2 Hbs originated from the horizontal gene transfers that accompanied the two
      generally accepted endosymbioses of a proteobacterium and a cyanobacterium with a
      eukaryote ancestor. In contrast, the origin of the group 2 2/2 Hbs unexpectedly
      appears to involve horizontal gene transfer from a bacterium ancestral to
      Chloroflexi, Deinococcales, Bacillli and Actinomycetes. We present additional
      results which indicate that the shared ancestry is likely to be with the
      Chloroflexi alone.

PMID- 21966567
TI  - Sleep homeostasis: Progress at a snail's pace.
AB  - We recently reported that a gastropod mollusc, Lymnaea stagnalis, exhibits a
      sleep-like quiescent state. However quiescence differed from mammalian sleep in
      that both circadian and homeostatic regulation seemed to be absent in the snail.
      In the present paper I explore the possibility that the clustered pattern of
      quiescence observed in the snail may provide insight into underlying regulatory
      mechanisms. Specifically, I hypothesize that clustering of quiescence arises from
      feedback modulation of a stochastic wake-quiescence oscillator. The feedback loop
      is postulated to limit cumulative wakefulness and to exert probabilistic
      modulation of wake duration. Computer simulations using this model succeeded in
      simulating snail wake-quiescence behavior, confirming the plausibility of the
      hypothesis. Implications of this analysis for our understanding of mechanisms and
      evolution of sleep homeostasis are discussed.

PMID- 21966568
TI  - Dissecting the electromechanical coupling mechanism of the motor-protein prestin.
AB  - Prestin, which is a member of the solute carrier 26 anion transporter family
      (SLC26A5), is a voltage-dependent membrane-based motor protein that confers
      electromotility on mammalian cochlear outer hair cells (OHCs).1 OHCs are a
      mammalian innovation, their presence2 and their endowment with functional prestin
      is essential for normal hearing of mammals.3 In order to clarify the molecular
      mechanism underlying the voltage-dependent motility of prestin, precise
      description of the relation between voltage-induced prestin-associated charge
      movement and the resulting cell displacement is essential. By simultaneously
      measuring voltage-dependent charge movement, which is manifested in the nonlinear
      capacitance (NLC) of the cell membrane, and voltage-induced OHC displacement, we
      provided compelling experimental evidence that prestin-associated charge movement
      and the resulting electromotility are fully coupled, and that prestin has at
      least two voltage-dependent conformational transition steps. These findings
      provide a basis for understanding the molecular mechanism of prestin. Here we
      discuss the relevance of our finding in the elucidation of the voltage-dependent
      motor mechanism of prestin, and speculate about possible voltage sensing
      mechanisms of the molecule.

PMID- 21966569
TI  - Splintrons in Giardia intestinalis: Spliceosomal introns in a split form.
AB  - The divergent eukaryotic unicellular organism Giardia intestinalis is an
      intestinal parasite in humans and various animals. An analysis of a draft genome
      sequence suggested that G. intestinalis has a much simpler genome organization
      and gene repertoire than those of other model eukaryotic organisms (e.g.,
      Arabidopsis and human). This general picture of the G. intestinalis genome
      seemingly agrees with the fact that only four spliceosomal (cis-spliced) introns
      have been identified in this organism to date. We have recently shown that G.
      intestinalis possesses a unique gene expression system incorporating spliceosome
      mediated trans-splicing. Some protein-coding genes in G. intestinalis are split
      into multiple pieces in the genome and each gene fragment is independently
      transcribed. Two particular pre-mRNAs directly interact with each other by
      forming an intermolecular-stem structure and are then trans-spliced into a mature
      mRNA by spliceosomes. We believe that this trans-splicing secondarily arose from
      the system that excises canonical (cis-splicing) introns. Based on these
      findings, we suspect that similar phenomena-split genes and post-transcriptional
      assemblage of their transcripts via trans-splicing-may be prevalent in more
      distinct eukaryotic lineages than previously known, particularly in organisms
      possessing "intron-poor" genomes.

PMID- 21966570
TI  - Expression of non-symbiotic hemoglobin 1 and 2 genes in rice (Oryza sativa)
      embryonic organs.
AB  - Rice (Oryza sativa) contains five copies of the non-symbiotic hemoglobin (hb)
      gene, namely hb1 to hb5. Previous analysis by RT-PCR revealed that rice hb1
      expresses in roots and leaves and hb2 expresses in leaves. However, it is not
      known whether or not hb1 and hb2 express in rice embryonic organs. Here, we
      report the expression of hb1 and hb2 genes in rice embryonic organs using RT-PCR
      and specific oligos for Hb1 and Hb2. Our results indicate that hb1 and hb2 genes
      express in embryonic organs in rice growing under normal conditions.
      Specifically, hb1 expresses in rice embryos and seminal roots, and hb2 expresses
      in embryos, coleoptiles and seminal roots. These observations suggest that Hb1
      and Hb2 coexist and function in rice embryonic organs.

PMID- 21966571
TI  - Serotonin as a mediator of cross-modal cortical reorganization.
AB  - When one type of sensory system is disrupted, other intact remaining sensory
      function can be improved. Although this form of plasticity, cross-modal
      plasticity, is widely known, the molecular and cellular mechanisms underlying it
      are poorly understood. In a recent study, we demonstrated that visual deprivation
      increases extracellular serotonin in the juvenile rat barrel cortex and resulted
      in facilitation of synaptic delivery of AMPA-type glutamate receptors (AMPARs) at
      layer4-2/3 synapses in the barrel cortex via the activation of serotonin 5HT2A/2C
      receptors and ERK. This caused sharpening of functional whisker-barrel map at
      layer2/3 of the barrel cortex. Thus, sensory dysfunction of one modality leads to
      improvement of remaining modalities by the refinement of cortical organization
      through serotonin signaling-mediated facilitation of synaptic AMPARs delivery.

PMID- 21966572
TI  - Specific ion fluxes generate cornea wound electric currents.
AB  - The corneal epithelium generates a significant trans-epithelial potential (TEP)
      which aids in maintaining cornea water balance and transparency. Injury to the
      cornea causes a short circuit of the TEP at the wound. The TEP in the intact
      epithelium around the wound acts like a battery, powering significant ion flux
      and electric current at the wound. These circulating endogenous currents generate
      an electric field orientated towards the wound, with the wound the cathode. Many
      cell types, including human corneal epithelial cells and keratinocytes, migrate
      to the cathode at physiological electric field strengths. Indeed, the electric
      signal is a powerful stimulator of cell migration, which appears to override
      other cues such as chemotaxis and wound void. These wound fields also have a
      dynamic timecourse of change after wounding. It has been assumed that wound
      electric fields are produced by passive leakage of ions from damaged cells and
      tissue. Could these fields be actively maintained and regulated as an active
      wound response? What are the molecular, ionic and cellular mechanisms underlying
      the wound electric currents?

PMID- 21966573
TI  - Novel tools for an old lineage: Population genomics for cycads.
AB  - With a ca. 300 million year-old evolutionary history, cycads are often perceived
      as "living fossils," relicts of their previously widespread dominance. Patterns
      of genetic variation for a member of the most basal cycad genus, Cycas
      micronesica, support the notion that cycads are a dynamic group with ongoing
      diversification. Herein we hypothesize that cycad's hefty genomes enable rapid
      adaptive change and facilitate specific beneficial interactions with varying
      assemblages of symbionts. Characterizing population-level genomic patterns of
      cycads and their symbionts, pollinators in particular, will enlighten our
      understanding of these mechanisms and of adaptive variation that underlies cycad
      evolution. In light of rapid climate and landscape change, cycads are a beacon
      for understanding the ecological processes that ultimately enable species long
      term survival.

PMID- 21966574
TI  - Emergence or self-organization?: Look to the soil population.
AB  - EMERGENCE IS NOT WELL DEFINED, BUT ALL EMERGENT SYSTEMS HAVE THE FOLLOWING
      CHARACTERISTICS: the whole is more than the sum of the parts, they show bottom-up
      rather top-down organization and, if biological, they involve chemical signaling.
      Self-organization can be understood in terms of the second and third stages of
      thermodynamics enabling these stages used as analogs of ecosystem functioning.
      The second stage system was suggested earlier to provide a useful analog of the
      behavior of natural and agricultural ecosystems subjected to perturbations, but
      for this it needs the capacity for self-organization. Considering the hierarchy
      of the ecosystem suggests that this self-organization is provided by the third
      stage, whose entropy maximization acts as an analog of that of the soil
      population when it releases small molecules from much larger molecules in dead
      plant matter. This it does as vigorously as conditions allow. Through this
      activity, the soil population confers self-organization at both the ecosystem and
      the global level. The soil population has been seen as both emergent and self
      organizing, supporting the suggestion that the two concepts are are so closely
      linked as to be virtually interchangeable. If this idea is correct one of the
      characteristics of a biological emergent system seems to be the ability to confer
      self-organization on an ecosystem or other entity which may be larger than
      itself. The beehive and the termite colony are emergent systems which share this
      ability.

PMID- 21966575
TI  - Video imaging of the sperm acrosome reaction during in vitro fertilization.
AB  - Mammalian spermatozoa become competent for fusion with oocytes while traveling
      through the female reproductive tract and the oocyte's extracellular investments.
      Recent studies highlighted the molecular mechanism of the sperm's interactions
      with the zona pellucida (ZP), the extracellular coat surrounding the oocyte.
      Fertilizing spermatozoa initiate the sperm acrosome reaction (AR), essential for
      zona penetration and fusion with the oocyte plasma membrane, before they reach
      the ZP. However, the exact condition of spermatozoa that leads to successful
      penetration of the ZP remains unknown. We performed microscopic observations of
      in vitro fertilization with genetically (EGFP) and chemically (antibody and
      lectin) labeled spermatozoa to monitor the progression of the AR. Spermatozoa
      exhibiting EGFP(-)/PNA(+) prior to binding to the ZP initiated zona penetration.
      This result suggests that spermatozoa that have undergone the AR are still
      capable of binding and penetrating the ZP.

PMID- 21966576
TI  - Glutathione is a crucial guardian of protein integrity in the brain upon nitric
      oxide imbalance.
AB  - GSH is mostly considered a non-enzymatic antioxidant that serves for modulating
      the redox status of protein thiols, detoxification and direct scavenging activity
      of oxyradicals. Within the cells, GSH has also the role to buffer the flux of
      nitric oxide (NO), which in the nervous system is physiologically produced being
      an important neuromodulator and neurotransmitter. However, this role of GSH in
      modulating NO toxicity is often considered of secondary importance. Recently, we
      confuted such assumption as we demonstrated that GSH depletion triggers a severe
      NO imbalance, which is the primary cause of neuronal death. Here we report that
      even a slight and non-toxic decrease of GSH in brain mice causes protein
      nitration that is reversed by inhibiting NO production. This evidence indicates
      that NO imbalance and the associated nitrosative hallmarks observed in
      neurodegenerative diseases as well as in health ageing are likely the consequence
      of the progressive decline of GSH.

PMID- 21966577
TI  - mDia3-EB1-APC: A connection between kinetochores and microtubule plus ends.
AB  - Kinetochores must continuously associate with dynamic microtubule plus ends, as
      they oscillate along the mitotic spindle. The molecular basis for the kinetochore
      to track microtubule plus ends remains unresolved. In a recent study, we have
      shown an essential role of the formin mDia3 in stable kinetochore microtubule
      attachment and metaphase chromosome alignment. This function is attributable to
      EB1-binding by mDia3, for replacing endogenous mDia3 with an EB1-binding
      deficient mutant results in chromosome misalignment. EB1 specifically targets to
      attached, antipoleward kinetochores with polymerizing microtubules during
      chromosome oscillation. Therefore, we speculate that the mDai3-EB1-APC complex
      formation may relay EB1 microtubule plus end-tracking activity to the
      kinetochore.

PMID- 21966578
TI  - Cortical localization of maternal embryonic leucine zipper kinase (MELK)
      implicated in cytokinesis in early xenopus embryos.
AB  - MELK has been implicated in a large variety of functions. Because its level is
      elevated in cancer tissues and it is involved in cell proliferation, MELK is
      considered as a potential therapeutic target for cancers. In a recent, study we
      have shown that MELK is involved in cytokinesis in early Xenopus laevis embryos.
      MELK dynamically accumulates at the cell cortex including a narrow band
      corresponding to the presumptive division furrow shortly before cytokinesis
      onset. MELK co-localizes and interacts with anillin an important regulator of
      cytokinesis. In addition, MELK overexpression interferes with accumulation at the
      cleavage furrow of activated Rho GTPase another crucial regulator of cytokinesis.
      Interestingly, our study also revealed that a transition implying a change in the
      direction of asymmetric furrow ingression occurs during early development. After
      this transition, MELK, as well as other proteins involved in cytokinesis, do not
      localize anymore as a band at the equatorial cortex but still localizes at the
      cell cortex. Our results indicate that cortical localization is an important
      feature of MELK in X. laevis embryos.

PMID- 21966579
TI  - Semi-automated three-dimensional reconstructions of individual neurons reveal
      cell type-specific circuits in cortex.
AB  - Despite a long history of anatomical mapping of neuronal networks, we are only
      beginning to understand the detailed three-dimensional (3D) organization of the
      cortical micro-circuitry. This is in part due to the lack of complete
      reconstructions of individual cortical neurons. Morphological studies are either
      performed on incomplete cells in vitro, or when performed in vivo, lack the
      necessary cellular resolution. We recently reconstructed the in vivo axonal and
      dendritic morphology of two types of L(ayer) 5 neurons from vibrissal cortex. The
      3D profiles of short-range as well as longrange projections indicate that L5
      slender-tufted and L5 thick-tufted neurons represent very different building
      blocks of the cortical circuitry. In this addendum to Oberlaender et al. (PNAS
      2011), we motivate our technical approach and the advancements this may give in
      reconstructing the cortical micro-circuitry.

PMID- 21966580
TI  - The role of M(3)-muscarinic receptor signaling in insulin secretion.
AB  - Recently, M(3)-muscarinic receptor (M3R) has been identified as the bona fide
      receptor responsible for the cholinergic regulation of glucose-induced insulin
      release. The molecular mechanisms of such regulation have also begun to be
      unravelled. These include the conventional G protein-dependent pathways involving
      calcium mobilization and activation of protein kinase C. In addition, recent
      studies also provided evidence for G protein-independent pathways in the
      regulation of insulin secretion by M3R. These include phosphorylation/arrestin
      dependent activation of protein kinase D1, Src family kinase-dependent activation
      of the sodium channel NALCN and the involvement of regulator of G protein
      signaling (RGS)-4. Time has now come to extend these studies which were done
      mainly in rodents to human and explore the potential for targeting such pathways
      at different levels for the treatment of diseases with impaired insulin secretion
      such as type II diabetes.

PMID- 21966581
TI  - Effects of intestinal microbiota on anxiety-like behavior.
AB  - The acquisition of intestinal microbiota in the immediate postnatal period has a
      defining impact on the development and function of many immune and metabolic
      systems integral to health and well-being. Recent research has shown that the
      presence of gut microbiota regulates the set point for hypothalamic-pituitary
      adrenal (HPA) axis activity.1 Accordingly, we sought to investigate if there were
      other changes of brain function such as behavioral alterations in germ free (GF)
      mice, and if so, to compare these to behavior of mice with normal gut microbiota.
      Our recent paper showed reduced anxietylike behavior in the elevated plus maze
      (EPM) in adult GF mice when compared to conventionally reared specific pathogen
      free (SPF) mice.2 Here, we present data collected when we next colonized the
      adult GF mice with SPF feces thereby introducing normal gut microbiota, and then
      reassessed anxiety-like behavior. Interestingly, the anxiolytic behavioral
      phenotype observed in GF mice persisted after colonization with SPF intestinal
      microbiota. These data show that gut-brain interactions are important to CNS
      development of stress systems and that a critical window may exist after which
      reconstitution of microbiota and the immune system does not normalize the
      behavioral phenotype.

PMID- 21966582
TI  - Who lives and who dies: Role of apoptosis in quashing developmental errors.
AB  - Apoptosis is essential for normal development. Large numbers of cells are
      eliminated by apoptosis in early neural development and during the formation of
      neural connections. However, our understanding of this life-or-death decision is
      incomplete, because it is difficult to identify dying cells by conventional
      strategies. Live imaging is powerful for studying apoptosis, because it can trace
      a death-fated cell throughout its lifetime. The Drosophila sensory organ
      development is a convenient system for studying neural-cell selection via lateral
      inhibition. We recently showed that about 20% of the differentiating neuronal
      cells die during sensory organ development, which results in the characteristic
      spatial patterning of the sensory organs. The eliminated differentiating neurons
      expressed neurogenic genes and high levels of activated Notch. Thus, live imaging
      allowed us to document the role of apoptosis in neural progenitor selection, and
      revealed that Notch activation is the mechanism determining which cells die
      during sensory organ development.

PMID- 21966583
TI  - Organizing the DV axis during planarian regeneration.
AB  - During regeneration, lost structures are rebuilt and perfectly integrated within
      the remaining non-injured tissues. This fascinating process captured the
      attention of one of the founders of modern genetics, T.H. Morgan. He was
      particularly interested in understanding regeneration in freshwater planarians,
      which can regenerate a whole animal from a small piece of their bodies. He
      performed numerous experiments to understand how polarity is re-established such
      that an anterior-facing wound regenerates a head whereas a posterior-facing wound
      regenerates a tail. However, it has not been until more than 100 years later that
      the molecules required to determine axial polarity have been identified. Several
      studies have now shown that the Wnt/beta-catenin and Hedgehog pathways are
      required for anteroposterior axis specification, whereas the establishment of the
      planarian dorsoventral (DV) axis relies on the Bone Morphogenetic Protein (BMP)
      pathway. Two recent papers have now uncovered additional conserved (anti
      dorsalizing morphogenetic protein) and novel (noggin-like genes) elements that
      regulate planarian DV axis regeneration. Here, we summarize those results and
      present new data and hypotheses to explain the role that noggin-like genes might
      play.

PMID- 21966584
TI  - In vitro recapitulation of aberrant protein inclusions in neurodegenerative
      diseases: New cellular models of neurodegenerative diseases.
AB  - Aberrant protein aggregates in affected brain cells of patients with
      neurodegenerative diseases are a well-known hallmark, but although the formation
      of these inclusions is an important pathogenic event, the mechanism involved
      remains unclear. We have recently established a simple method to introduce
      protein fibrils into cultured cells as seeds for protein aggregation, and we
      showed that intracellular soluble alpha-synuclein or tau can aggregate in
      cultured cells dependently upon seeds introduced in this way. Seeded aggregation
      of alpha-synuclein induced necrotic cell death, which was suppressed by the
      addition of various polyphenols. Our cellular models are expected to be valuable
      tools not only for elucidating the molecular mechanisms of onset of
      neurodegenerative diseases, but also for drug discovery.

PMID- 21966585
TI  - Utilizing Lifetimes to Suppress Random Coil Features in 2D IR Spectra of
      Peptides.
AB  - We report that the waiting time delay in 2D IR pulse sequences can be used to
      suppress signals from structurally disordered regions of amyloid fibrils. At a
      waiting time delay of 1.0 ps, the random coil vibrational modes of amylin fibrils
      are no longer detectable, leaving only the sharp excitonic vibrational features
      of the fibril beta-sheets. Isotope labeling with (13)C(18)O reveals that
      structurally disordered residues decay faster than residues protected from
      solvent. Since structural disorder is usually accompanied by hydration, we
      conclude that the shorter lifetimes of random-coil residues is due to solvent
      exposure. These results indicate that 2D IR pulse sequences can utilize the
      waiting time to better resolve solvent-protected regions of peptides and that
      local mode lifetimes should be included in simulations of 2D IR spectra.

PMID- 21966586
TI  - Assessing principal component regression prediction of neurochemicals detected
      with fast-scan cyclic voltammetry.
AB  - Principal component regression is a multivariate data analysis approach routinely
      used to predict neurochemical concentrations from in vivo fast-scan cyclic
      voltammetry measurements. This mathematical procedure can rapidly be employed
      with present day computer programming languages. Here, we evaluate several
      methods that can be used to evaluate and improve multivariate concentration
      determination. The cyclic voltammetric representation of the calculated
      regression vector is shown to be a valuable tool in determining whether the
      calculated multivariate model is chemically appropriate. The use of Cook's
      distance successfully identified outliers contained within in vivo fast-scan
      cyclic voltammetry training sets. This work also presents the first direct
      interpretation of a residual color plot and demonstrated the effect of peak
      shifts on predicted dopamine concentrations. Finally, separate analyses of
      smaller increments of a single continuous measurement could not be concatenated
      without substantial error in the predicted neurochemical concentrations due to
      electrode drift. Taken together, these tools allow for the construction of more
      robust multivariate calibration models and provide the first approach to assess
      the predictive ability of a procedure that is inherently impossible to validate
      because of the lack of in vivo standards.

PMID- 21966587
TI  - Identification of a novel selective serotonin reuptake inhibitor by coupling
      monoamine transporter-based virtual screening and rational molecular
      hybridization.
AB  - Ligand virtual screening (VS) using the vestibular binding pocket of a 3-D
      monoamine transporter (MAT) computational model followed by in vitro pharmacology
      led to the identification of a human serotonin transporter (hSERT) inhibitor with
      modest affinity (hSERT K(i) = 284 nM). Structural comparison of this VS
      elucidated compound, denoted MI-17, to known SERT ligands led to the rational
      design and synthesis of DJLDU-3-79, a molecular hybrid of MI-17 and dual SERT/5
      HT(1A) receptor antagonist SSA-426. Relative to MI-17, DJLDU-3-79 displayed 7
      fold improvement in hSERT binding affinity and a 3-fold increase in [(3)H]
      serotonin uptake inhibition potency at hSERT/HEK cells. This hybrid compound
      displayed a hSERT:hDAT selectivity ratio of 50:1, and a hSERT:hNET (human
      norepinephrine transporter) ratio of >200:1. In mice, DJLDU-3-79 decreased
      immobility in the tail suspension test comparable to the SSRI fluvoxamine,
      suggesting that DJLDU-3-79 may possess antidepressant properties. This proof of
      concept study highlights MAT virtual screening as a powerful tool for identifying
      novel inhibitor chemotypes and chemical fragments for rational inhibitor design.

PMID- 21966588
TI  - Structure-Composition-Property Relationships in Polymeric Amorphous Calcium
      Phosphate-Based Dental Composites.
AB  - Our studies of amorphous calcium phosphate (ACP)-based materials over the last
      decade have yielded bioactive polymeric composites capable of protecting teeth
      from demineralization or even regenerating lost tooth mineral. The anti
      cariogenic/re-mineralizing potential of these ACP composites originates from
      their propensity, when exposed to the oral environment, to release in a sustained
      manner sufficient levels of mineral-forming calcium and phosphate ions to promote
      formation of stable apatitic tooth mineral. However, the less than optimal ACP
      filler/resin matrix cohesion, excessive polymerization shrinkage and water
      sorption of these experimental materials can adversely affect their
      physicochemical and mechanical properties, and, ultimately, limit their lifespan.
      This study demonstrates the effects of chemical structure and composition of the
      methacrylate monomers used to form the matrix phase of composites on degree of
      vinyl conversion (DVC) and water sorption of both copolymers and composites and
      the release of mineral ions from the composites. Modification of ACP surface via
      introducing cations and/or polymers ab initio during filler synthesis failed to
      yield mechanically improved composites. However, moderate improvement in
      composite's mechanical stability without compromising its remineralization
      potential was achieved by silanization and/or milling of ACP filler. Using
      ethoxylated bisphenol A dimethacrylate or urethane dimethacrylate as base
      monomers and adding moderate amounts of hydrophilic 2-hydroxyethyl methacrylate
      or its isomer ethyl-alpha-hydroxymethacrylate appears to be a promising route to
      maximize the remineralizing ability of the filler while maintaining high DVC.
      Exploration of the structure/composition/property relationships of ACP fillers
      and polymer matrices is complex but essential for achieving a better
      understanding of the fundamental mechanisms that govern dissolution/re
      precipitation of bioactive ACP fillers, and, ultimately, the suitability of the
      composites for clinical evaluation.

PMID- 21966589
TI  - Probiotics for the control of parasites: an overview.
AB  - Probiotics are defined as live organisms, which confer benefits to the host.
      Their efficiency was demonstrated for the treatment of gastrointestinal
      disorders, respiratory infections, and allergic symptoms, but their use is mostly
      limited to bacterial and viral diseases. During the last decade, probiotics as
      means for the control of parasite infections were reported covering mainly
      intestinal diseases but also some nongut infections, that are all of human and
      veterinary importance. In most cases, evidence for a beneficial effect was
      obtained by studies using animal models. In a few cases, cellular interactions
      between probiotics and pathogens or relevant host cells were also investigated
      using in vitro culture systems. However, molecular mechanisms mediating the
      beneficial effects are as yet poorly understood. These studies indicate that
      probiotics might indeed provide a strain-specific protection against parasites,
      probably through multiple mechanisms. But more unravelling studies are needed to
      justify probiotic utilisation in therapeutics.

PMID- 21966590
TI  - Modeling the effects of relapse in the transmission dynamics of malaria
      parasites.
AB  - Often regarded as "benign," Plasmodium vivax infections lay in the shadows of the
      much more virulent P. falciparum infections. However, about 1.98 billion people
      are at risk of both parasites worldwide, stressing the need to understand the
      epidemiology of Plasmodium vivax, particularly under the scope of decreasing P.
      falciparum prevalence and ecological interactions between both species. Two
      epidemiological observations put the dynamics of both species into perspective:
      (1) ACT campaigns have had a greater impact on P. falciparum prevalence. (2)
      Complete clinical immunity is attained at younger ages for P. vivax, under
      similar infection rates. We systematically compared two mathematical models of
      transmission for both Plasmodium species. Simulations suggest that an ACT therapy
      combined with a hypnozoite killing drug would eliminate both species. However, P.
      vivax elimination is predicted to be unstable. Differences in age profiles of
      clinical malaria can be explained solely by P. vivax's ability to relapse, which
      accelerates the acquisition of clinical immunity and serves as an immunity
      boosting mechanism. P. vivax transmission can subsist in areas of low mosquito
      abundance and is robust to drug administration initiatives due to relapse, making
      it an inconvenient and cumbersome, yet less lethal alternative to P. falciparum.

PMID- 21966591
TI  - Revisiting the Marrow Metabolic Changes after Chemotherapy in Lymphoma: A Step
      towards Personalized Care.
AB  - Purpose. The aims were to correlate individual marrow metabolic changes after
      chemotherapy with bone marrow biopsy (BMBx) for its potential value of
      personalized care in lymphoma. Methods. 26 patients (mean age, 58 +/- 15 y; 13
      female, 13 male) with follicular lymphoma or diffuse large B-cell lymphoma,
      referred to FDG-PET/CT imaging, who had BMBx from unilateral or bilateral iliac
      crest(s) before chemotherapy, were studied retrospectively. The maximal
      standardized uptake value (SUV) was measured from BMBx site over the same area on
      both initial staging and first available restaging FDG-PET/CT scan. Results. 35
      BMBx sites in 26 patients were evaluated. 12 of 35 sites were BMBx positive with
      interval decrease in SUV in 11 of 12 sites (92%). The remaining 23 of 35 sites
      were BMBx negative with interval increase in SUV in 21 of 23 sites (91%). The
      correlation between SUV change over the BMBx site before and after chemotherapy
      and BMBx result was significant (P < 0.0001). Conclusions. This preliminary
      result demonstrates a strong correlation between marrow metabolic changes (as
      determined by FDG PET) after chemotherapy and bone marrow involvement proven by
      biopsy. This may provide a retrospective means of personalized management of
      marrow involvement in deciding whether to deliver more extended therapy or closer
      followup of lymphoma patients.

PMID- 21966592
TI  - Why Are Native Hawaiians Underrepresented in Hawai'i's Older Adult Population?
      Exploring Social and Behavioral Factors of Longevity.
AB  - Native Hawaiians comprise 24.3% of Hawai'i's population, but only 12.6% of the
      state's older adults. Few published studies have compared health indicators
      across ethnicities for the state's older adult population or focused on
      disparities of Native Hawaiian elders. The current study examines data from two
      state surveillance programs, with attention to cause of death and social
      behavioral factors relevant to elders. Findings reveal that Native Hawaiians have
      the largest years of productive life lost and the lowest life expectancy, when
      compared to the state's other major ethnic groups. Heart disease and cancer are
      leading causes of premature mortality. Native Hawaiian elders are more likely to
      report behavioral health risks such as smoking and obesity, live within/below 100
      199% of the poverty level, and find cost a barrier to seeking care. Indicated is
      the need for affordable care across the lifespan and health services continuum.
      Future research might explain behavioral factors as influenced by social
      determinants, including historical trauma on Native Hawaiian longevity.

PMID- 21966594
TI  - Understanding methods for estimating HIV-associated maternal mortality.
AB  - The impact of HIV on maternal mortality and more broadly on the health of women,
      remains poorly documented and understood. Two recent reports attempt to address
      the conceptual and methodological challenges that arise in estimating HIV-related
      maternal mortality and trends. This paper presents and compares the methods and
      discusses how they affect estimates at global and regional levels. Country
      examples of likely patterns of mortality among women of reproductive age are
      provided to illustrate the critical interactions between HIV and complications of
      pregnancy in high-HIV-burden countries. The implications for collaboration
      between HIV and reproductive health programmes are discussed, in support of
      accelerated action to reach the Millennium Development Goals and improve the
      health of women.

PMID- 21966593
TI  - Is there a reversal in the effect of obesity on mortality in old age?
AB  - Studies of obesity and its relationship with mortality risk in older persons have
      yielded conflicting results. We aimed to examine the age-related associations
      between obesity and mortality in older persons. Data were drawn from the Cross
      Sectional and Longitudinal Aging Study (CALAS), a national survey of a random
      sample of older Jewish persons in Israel conducted during 1989-1992. Analyses
      included 1369 self-respondent participants aged 75-94 from the Cross-Sectional
      and Longitudinal Aging Study (CALAS). Mortality data at 20-year followup were
      recorded from the Israeli National Population Registry. Obesity was significantly
      predictive of higher mortality for persons aged 75-84, but from age 85 onwards,
      obesity had a protective effect on mortality albeit at a nonsignificant level.
      Being underweight was consistently predictive of mortality. Findings suggest that
      the common emphasis on avoiding obesity may not apply to those advancing towards
      old-old age, at least as far as mortality is concerned.

PMID- 21966595
TI  - Novel Conjugates of 1,3-Diacylglycerol and Lipoic Acid: Synthesis, DPPH Assay,
      and RP-LC-MS-APCI Analysis.
AB  - 1,3-Diacylglycerol is known to reduce body weight and fat deposits in humans.
      alpha-Lipoic acid is a potent antioxidant and effective against many pathological
      conditions, including obesity and related metabolic syndromes. The present work
      is based on the hypothesis that the hybrid molecules of 1,3-diacylglycerol and
      lipoic acid possess synergistic and/or additive effects compared with the parent
      compounds against obesity, overweight, and related metabolic syndromes.
      Laboratory scale synthesis of 1,3-dioleoyl-2-lipoyl-sn-glycerol (yield 80%) and
      1,3-dioleoyl-2-dihydrolipoyl-sn-glycerol (yield 70%) was performed for the first
      time and supported by NMR and MS data. Free radical scavenging capacity of the
      conjugates was assayed using DPPH test. A remarkably high in vitro free radical
      scavenging capacity was demonstrated for the 1,3-dioleoyl-2-dihydrolipoyl-sn
      glycerol (EC(50) value 0.21). RP-HPLC-MS-APCI analysis showed satisfactory
      separation between the conjugates (R~1). Protonated molecular ion of the
      conjugates at m/z 809 and m/z at 811, respectively, and their characteristic
      fragment ions were abundant.

PMID- 21966596
TI  - Enhancement of Bacillus subtilis Lipopeptide Biosurfactants Production through
      Optimization of Medium Composition and Adequate Control of Aeration.
AB  - Interest in biosurfactants has increased considerably in recent years, as they
      are potentially used in many commercial applications in petroleum,
      pharmaceuticals, biomedical, and food processing industries. Since improvement of
      their production was of great importance to reduce the final coast, cultural
      conditions were analyzed to optimize biosurfactants production from Bacillus
      subtilis SPB1 strain. A high yield of biosurfactants was obtained from a culture
      of B. subtilis using carbohydrate substrate as a carbon source; among
      carbohydrates, glucose enhanced the best surfactin production. The optimum
      glucose concentration was 40 g/L. Higher amount of biosurfactants was obtained
      using 5 g/L of urea as organic nitrogen source and applying C/N ratio of 7 with
      ammonium chloride as inorganic nitrogen source. The highest amount of
      biosurfactants was recorded with the addition of 2% kerosene. Moreover, it was
      shown, using an automated full-controlled 2.6 L fermenter, that aeration of the
      medium, which affected strongly the growth regulated biosurfactants synthesis by
      the producing cell. So that, low or high aerations lead to a decrease of
      biosurfactants synthesis yields. It was found that when using dissolved oxygen
      saturation of the medium at 30%, biosurfactants production reached 4.92 g/L.

PMID- 21966597
TI  - Cerebrospinal Fluid Levels of sAPPalpha and sAPPbeta in Lewy Body and Alzheimer's
      Disease: Clinical and Neurochemical Correlates.
AB  - We measured cerebrospinal fluid (CSF) levels of the soluble isoforms of amyloid
      precursor protein (APP; sAPPalpha sAPPbeta) and other CSF biomarkers in 107
      patients with Alzheimer's disease (AD), dementia with Lewy body dementia (DLB),
      Parkinson's disease dementia (PDD), and normal controls (NC) using commercial
      kits. DLB and PDD were combined in a Lewy body dementia group (LBD). No
      differences were observed in sAPPalpha and sAPPbeta levels between the groups.
      Significant correlations were observed between sAPPalpha and sAPPbeta and between
      sAPPbeta and Mini-Mental State Examination scores in the total group analysis as
      well as when LBD and AD groups were analyzed separately. sAPPalpha and sAPPbeta
      levels correlated with Abeta38, Abeta40, Abeta42, and Tau in the LBD group. In
      AD, sAPPalpha correlated with p-Tau and sAPPbeta with Abeta40. The differential
      association between sAPPalpha and sAPPbeta with Abeta and Tau species between LBD
      and AD groups suggests a possible relationship with the underlying pathologies in
      LBD and AD.

PMID- 21966598
TI  - Effects of walking endurance reduction on gait stability in patients with stroke.
AB  - Control of gait is usually altered following stroke, and it may be further
      compromised by overexertion and fatigue. This study aims to quantitatively assess
      patients' gait stability during six-minute walking, measuring upper body
      accelerations of twenty patients with stroke (64 +/- 13 years old) and ten age
      matched healthy subjects (63 +/- 10 years old). Healthy subjects showed a steady
      gait in terms of speed and accelerations over the six minutes. Conversely, the
      patients unable to complete the test (n = 8) progressively reduced their walking
      speed (-22 +/- 11%, confidence interval CI(95%): -13, -29%, P = 0.046). Patients
      able to complete the test (n = 12) did not vary their walking speed over time (P
      = 0.493). However, this ability was not supported by an adequate capacity to
      maintain their gait stability, as shown by a progressive increase of their upper
      body accelerations (+5 +/- 11%, CI(95%): -1; +12%, P = 0.010). Walking endurance
      and gait stability should be both quantitatively assessed and carefully improved
      during the rehabilitation of patients with stroke.

PMID- 21966599
TI  - Physical activity in hospitalised stroke patients.
AB  - The aim of this paper was to examine the amount and type of physical activity
      engaged in by people hospitalised after stroke. Method. We systematically
      reviewed the literature for observational studies describing the physical
      activity of stroke patients. Results. Behavioural mapping, video recording and
      therapist report are used to monitor activity levels in hospitalised stroke
      patients in the 24 included studies. Most of the patient day is spent inactive
      (median 48.1%, IQR 39.6%-69.3%), alone (median 53.7%, IQR 44.2%-60.6%) and in
      their bedroom (median 56.5%, IQR 45.2%-72.5%). Approximately one hour per day is
      spent in physiotherapy (median 63.2 minutes, IQR 36.0-79.5) and occupational
      therapy (median 57.0 minutes, IQR 25.1-58.5). Even in formal therapy sessions
      limited time is spent in moderate to high level physical activity. Low levels of
      physical activity appear more common in patients within 14 days post-stroke and
      those admitted to conventional care. Conclusions. Physical activity levels are
      low in hospitalised stroke patients. Improving the description and classification
      of post stroke physical activity would enhance our ability to pool data across
      observational studies. The importance of increasing activity levels and the
      effectiveness of interventions to increase physical activity after stroke need to
      be tested further.

PMID- 21966600
TI  - Assessment of bronchodilator responsiveness after methacholine-induced
      bronchoconstriction.

PMID- 21966601
TI  - Current control and future risk in asthma management.
AB  - Despite international and national guidelines, poor asthma control remains an
      issue. Asthma exacerbations are costly to both the individual, and the healthcare
      provider. Improvements in our understanding of the therapeutic benefit of asthma
      therapies suggest that, in general, while long-acting bronchodilator therapy
      improves asthma symptoms, the anti-inflammatory activity of inhaled
      corticosteroids reduces acute asthma exacerbations. Studies have explored factors
      which could be predictive of exacerbations. A history of previous exacerbations,
      poor asthma control, poor inhaler technique, a history of lower respiratory tract
      infections, poor adherence to medication, the presence of allergic rhinitis,
      gastro-oesophageal reflux disease, psychological dysfunction, smoking and obesity
      have all been implicated as having a predictive role in the future risk of asthma
      exacerbation. Here we review the current literature and discuss this in the
      context of primary care management of asthma.

PMID- 21966602
TI  - Chronic rhinosinusitis: therapeutic efficacy of anti-inflammatory and antibiotic
      approaches.
AB  - Despite the high prevalence of chronic rhinosinusitis (CRS) worldwide, the exact
      pathogenesis of the disease remains unknown. Even with therapeutic intervention,
      treatment response is often only partial and frequently ineffective. The
      inability to define exact disease phenotypes in relation to specific disease
      mechanisms has led to a broad based approach with both anti-inflammatory and anti
      microbial intervention. The clinical efficacy of such current therapeutic
      strategies is highlighted and the urgent need for further robust therapeutic
      intervention studies in CRS is discussed in this article.

PMID- 21966603
TI  - The search for genetic variants and epigenetics related to asthma.
AB  - For the past two decades, a huge number of genetic studies have been conducted to
      identify the genetic variants responsible for asthma risk. Several types of
      genetic and genomic approaches, including linkage analysis, candidate gene single
      nucleotide polymorphism studies, and whole genome-wide association studies have
      been applied. In this review article, the results of these approaches are
      summarized, and their limitations are discussed. Additionally, perspectives for
      applying upcoming new epigenetic or genomic technologies, such as copy number
      variation, are introduced to increase our understanding of new omic approaches to
      asthma genetics.

PMID- 21966604
TI  - Assessment of bronchodilator responsiveness following methacholine-induced
      bronchoconstriction in children with asthma.
AB  - PURPOSE: The aim of this study was to investigate bronchodilator responsiveness
      (BDR) following methacholine-induced bronchoconstriction and to determine
      differences in BDR according to clinical parameters in children with asthma.
      METHODS: The methacholine challenge test was performed in 145 children with mild
      to moderate asthma, and the provocative concentration causing a 20% decline in
      FEV1 (PC20) was determined. Immediately after the challenge test, patients were
      asked to inhale short-acting beta2-agonists (SABAs) to achieve BDR, which was
      assessed as the change in FEV1% predicted*100/post-methacholine FEV1% predicted.
      For each subject, the asthma medication, blood eosinophil count, serum total IgE,
      serum eosinophil cationic protein level, and skin prick test result were
      assessed. RESULTS: The FEV1 (mean+/-SD) values of the 145 patients were 90.5+/
      10.9% predicted, 64.2+/-11.5% predicted, and 86.2+/-11.2% predicted before and
      after methacholine inhalation, and following the administration of a SABA,
      respectively. The BDR did not differ significantly according to asthma
      medication, age, or gender. However, BDR in the atopy group (37.4+/-17.7%) was
      significantly higher than that in the non-atopy group (30.5+/-10.7%; P=0.037).
      Patients with blood eosinophilia (38.6+/-18.1%) displayed increased BDR compared
      with patients without eosinophilia (32.0+/-13.8%; P=0.037). CONCLUSIONS: In
      children with mild to moderate asthma, the responsiveness to short-acting
      bronchodilators after methacholine-induced bronchoconstriction was not related to
      asthma medication, but was higher in children with atopy and/or peripheral blood
      eosinophilia.

PMID- 21966605
TI  - The relationship between serum 25 hydroxy vitamin d levels and asthma in
      children.
AB  - PURPOSE: Asthma and other allergic disorders have increased over the past decades
      in nearly all nations. Many studies have suggested the role of vitamin D
      deficiency in both T-helper1 and T-helper2 diseases; however, the association
      between vitamin D, allergy, and asthma remains uncertain. In this study, the
      associations of 25-hydroxy vitamin D3 levels with asthma and with the severity of
      asthma were evaluated. METHODS: This cross-sectional study was conducted on 50
      asthmatic children and 50 healthy controls aged 6-18 years. Serum 25-hydroxy
      vitamin D3 levels were determined and compared between the two groups. The
      relationship between serum vitamin D levels and pulmonary function test outcomes
      and eosinophil counts were examined in asthmatic patients. RESULTS: Univariate
      analysis of the relationship between asthma and vitamin D showed that decreased
      vitamin D levels were associated with significantly increased odds of asthmatic
      state (P=0.002). In a multivariate analysis after adjustment for age, body mass
      index, and sex, the relationship between vitamin D and asthma increased. In
      asthmatic patients, 25-hydroxy vitamin D levels had direct and significant
      correlations with both predicted FEV1 (R(2)=0.318; P=0.024) and FEV1/FVC
      (R(2)=0.315; P=0.026). There were no associations between vitamin D level and
      eosinophil counts, duration of disease, and the number of hospitalization or
      unscheduled visits in the previous year (P>0.05). CONCLUSIONS: These results
      showed that serum 25-hydroxy vitamin D levels were inversely associated with
      asthma, and there was a direct and significant relationship between vitamin D
      levels and pulmonary function test outcomes in asthmatic children. An
      interventional study in asthmatic patients with low serum vitamin D concentration
      may establish a causal relationship between asthma and vitamin D.

PMID- 21966606
TI  - Diagnostic value of clinical parameters in the prediction of aspirin-exacerbated
      respiratory disease in asthma.
AB  - PURPOSE: Aspirin-exacerbated respiratory disease (AERD) has attracted a great
      deal of attention because of its association with increased asthma severity.
      However, oral aspirin challenge (OAC) to diagnose AERD is a time-consuming
      procedure, and some patients experience serious complications. Thus, we evaluated
      diagnostic values of non-invasive clinical parameters to predict AERD in
      asthmatic patients. METHODS: A total of 836 Korean subjects were recruited from
      an asthma cohort. They underwent OAC, and clinical parameters including the
      history of aspirin hypersensitivity, nasal polyposis, and chronic sinusitis of
      aspirin-tolerant asthma (ATA) and AERD asthmatic patients were compared. RESULTS:
      Significant differences (P<0.01) were found in eight parameters: age at
      diagnosis, body mass index, FEV1%, PC20, history of urticaria, nasal polyps,
      chronic sinusitis, and history of aspirin hypersensitivity. After logistic
      regression analysis based on the eight clinical parameters, nasal polyps, history
      of aspirin intolerance, sinusitis, and log [PC20 methacholine] remained
      significantly associated with AERD (P<0.05). The sensitivity and specificity of
      the history of aspirin hypersensitivity to predict AERD were 64.7% and 92.0%,
      respectively, and the positive and negative predictive values were 56.9% and
      94.1%, respectively. Overall, the accuracy of the test was 88.2%. The accuracy of
      the tests for nasal polyps and chronic sinusitis were 67.3% and 60.4%,
      respectively. CONCLUSIONS: Among clinical parameters associated with AERD, the
      history of aspirin hypersensitivity has the best positive and negative predictive
      values for the oral aspirin challenge test. Because the false-positive and 
      negative rates were still high, additional non-invasive methods are needed to
      reduce the rate of false outcomes.

PMID- 21966607
TI  - Asthma-predictive genetic markers in gene expression profiling of peripheral
      blood mononuclear cells.
AB  - PURPOSE: We sought to identify asthma-related genes and to examine the potential
      of these genes to predict asthma, based on expression levels. METHODS: The
      subjects were 42 asthmatics and 10 normal healthy controls. PBMC RNA was
      subjected to microarray analysis using a 35K array; t-tests were used to identify
      genes that were expressed differentially between the two groups. A multiple
      logistic regression analysis was applied to the differentially expressed genes,
      and area under the curve (AUC) values from receiver operating characteristic
      (ROC) curves were obtained. RESULTS: In total, 170 genes were selected using the
      following criteria: P<=0.001 and >=2-fold change. Among these genes, 57 were up
      regulated and 113 were down-regulated in asthmatics versus normal controls. A
      multiple logistic regression analysis was done using more stringent criteria
      (P<=0.001 and >=5-fold change), and eight genes were selected as candidate asthma
      biomarkers. Using these genes, 255 models (2(8)-1) were generated. Among them,
      only 85 showed P<=0.05 by multiple logistic regression analysis. Based on the
      AUCs from ROC curves for the 85 models, we found that the best model consisted of
      the genes MEPE, MLSTD1, and TRIM37. The model showed 0.9928 of the AUC with 98%
      sensitivity and 80% specificity. CONCLUSIONS: MEPE, MLSTD1, and TRIM37 may be
      useful biomarkers for asthma.

PMID- 21966608
TI  - Polymorphisms of Aspirin-Metabolizing Enzymes CYP2C9, NAT2 and UGT1A6 in Aspirin
      Intolerant Urticaria.
AB  - Acetyl salicylic acid (ASA) is metabolized by UDP-glucuronosyltransferase 1A6
      (UGT1A6), cytochrome P4502C9 (CYP2C9), and N-acetyl transferase 2 (NAT2).
      Variations in the activities of these enzymes may modulate adverse ASA-related
      symptoms such as urticaria. We examined whether polymorphisms in the UGT1A6,
      CYP2C9, and NAT2 genes are related to ASA-intolerant urticaria (AIU). The
      genotypes of 148 subjects with AIU (AIU group) and 260 normal healthy control
      subjects (NC group) were analyzed with respect to the following single nucleotide
      polymorphisms: CYP2C9 -1188T>C and CYP2C9(*)3A1075C; UGT1A6 T181A A>G and UGT1A6
      R184S A>C; and NAT2 9796A>T, NAT2 197G>A, NAT2 286G>A, NAT2 9601A>G, and NAT2
      9306A>G. There were significant differences in the allele frequencies for the
      CYP2C9 polymorphisms between the two groups. The frequency of the minor allele
      CYP2C9 -1188T>C was significantly higher in the AIU group than in the NC group
      (P=0.005). The frequency of the variant genotype CC was higher in the AIU group
      compared with the controls in both the co-dominant (P=0.007) and recessive models
      (P=0.012). The frequency of haplotype 2 [CA] was also significantly higher in the
      AIU group in both the co-dominant (P=0.006) and dominant models (P=0.012). There
      was no significant difference in genotype frequencies for any of the UGT1A6 or
      NAT2 polymorphisms between the two groups. Clinical parameters did not differ
      according to genotype. These results suggest that the C allele of CYP2C9 -1188T>C
      may be associated with AIU.

PMID- 21966609
TI  - Acute urticaria induced by oral methylprednisolone.
AB  - Although corticosteroids have immunosuppressive, anti-inflammatory, and anti
      allergic effects, allergic reactions are rare. We report a case involving a 52
      year-old-female with acute urticaria caused by oral methylprednisolone. The
      patient had experienced aspirin-exacerbated respiratory disease (AERD) for 13
      years with frequent asthma exacerbations. Symptoms of asthma exacerbations
      improved with short-term treatments of systemic steroids, including
      methylprednisolone or deflazacort, which had been well tolerated. However, the
      current admission was prompted by the development of acute generalized urticaria
      following the oral ingestion of methylprednisolone (8 mg) for relief of symptoms.
      An oral provocation test with 4 mg oral methylprednisolone led to generalized
      urticaria 20 minutes later, confirming the causal association. This is the first
      report of acute urticaria caused by oral methylprednisolone in a patient with
      AERD.

PMID- 21966610
TI  - Bronchospasm and anaphylactic shock following lidocaine aerosol inhalation in a
      patient with butane inhalation lung injury.
AB  - Allergic reactions to local anesthetics are very rare and represent <1% of all
      adverse local anesthetics reactions. A 54-year-old man was admitted to the
      hospital in the winter because of shortness of breath. The patient reportedly had
      an inhalation lung injury due to butane gas fuel. On the fifth day, he developed
      an asthmatic attack and anaphylactic shock immediately after lidocaine aerosol
      administration to prepare for bronchoscopy to confirm an acute inhalational lung
      injury diagnosis. Cardiopulmonary resuscitation was performed immediately after
      respiratory arrest, and the patient was admitted to the intensive care unit
      intubated and on a ventilator. He was extubated safely on the third post
      cardiopulmonary resuscitation day. These observations suggest that aerosol
      lidocaine anesthesia may cause airway narrowing and anaphylactic shock.
      Practitioners should be aware of this potential complication. We report on this
      case with a brief review of the literature.

PMID- 21966611
TI  - Erratum: changes in the prevalence of childhood asthma in seoul from 1995 to 2008
      and its risk factors.
AB  - [This corrects the article on p. 27 in vol. 3, PMID: 21217922.].

PMID- 21966612
TI  - Attrition in a Multidisciplinary Pediatric Weight Management Clinic.
AB  - BACKGROUND: Pediatric weight management clinics experience significant dropout,
      and few studies have investigated this problem. The objective of this study was
      to identify family and clinic characteristics associated with attrition from a
      tertiary care pediatric weight management clinic.  METHODS: This was a
      prospective and retrospective clinical database study of a multidisciplinary
      clinic for obese children 2-18 years with a weight-related co-morbidity. All
      patients seen between November, 2007, and July, 2009, were included.
      Characteristics of Active and Inactive families were compared using chi-squared
      and t-tests, and logistic regression was used to identify independent correlates
      of program status. A one-page survey was mailed to all Inactive families. 
      RESULTS: A total of 133 patients were seen during the study period. Their mean
      age was 12 years old, mean BMI was 38 kg/m(2), 53% were female, 52% represented
      racial/ethnic minorities, and 50% were Medicaid recipients. In all, 32% dropped
      out of treatment. Inactive children had significantly lower BMI z-scores, were
      older, and were more likely to have poor school performance than active children.
      Similar results were found on regression analysis: Children with higher BMI z
      scores, commercial insurance, average school performance, and a major weight
      related co-morbidity were less likely to be inactive. The most common parent
      reported reasons for dropping out were: Child not wanting to make changes, weight
      not improving, child desired to leave program, and program not meeting parent or
      child's expectations.  CONCLUSIONS: Attrition from pediatric weight management
      treatment is high, with age, weight, school performance, and health associated
      with dropout. Parents mostly reported child-related issues, including lack of
      weight loss, as reasons for dropout.

PMID- 21966613
TI  - X-ray Digital Linear Tomosynthesis Imaging for Artificial Pulmonary Nodule
      Detection.
AB  - The purpose of this paper is to identify indications for volumetric X-ray digital
      linear tomosynthesis (DLT) with single- and dual-energy subtraction techniques
      for artificial pulmonary nodule detection and compare X-ray DLT, X-ray digital
      radiography, and computed tomography.

PMID- 21966614
TI  - Traumatic ectopic dislocation of testis.
AB  - Traumatic ectopic dislocation of testis is a rare occurrence and usually occurs
      following a motorcycle collision, in what is referred to as "fuel tank injury".
      Early identification and subsequent surgical management is of utmost importance
      to maintain normal spermatogenesis in the dislocated testis. In appropriate
      clinical setting, scrotal ultrasound examination with gray-scale and color flow
      Doppler imaging is the method of choice for diagnosis. Computed tomography of the
      abdomen is a useful adjunct procedure. We report a case of traumatic testicular
      dislocation with partial testicular torsion following a motorcycle collision,
      diagnosed with imaging, and subsequently confirmed on surgery.

PMID- 21966615
TI  - Macrodystrophia lipomatosa: radiologic-pathologic correlation.
AB  - Macrodystrophia lipomatosa (MDL) is a rare cause of congenital macrodactyly,
      characterised by progressive proliferation of all mesenchymal elements, with
      disproportionate increase in fibro-adipose tissue. It occurs most frequently in
      lower limbs along the distribution of the medial plantar nerve. MDL presents as
      localised gigantism of the hand or foot and comes to clinical attention for
      cosmetic reasons, mechanical problems secondary to degenerative joint disease, or
      development of neurovascular compression. Here, we report a case of MDL, with
      altered soft tissue growth due to an earlier surgery, making clinical diagnosis
      difficult. However, with a complete radio-clinical work-up and review of the
      history, a provisional diagnosis of MDL was made, which was confirmed by
      histopathology and during surgery.

PMID- 21966616
TI  - Sonographic upper gastrointestinal series in the vomiting infant: how we do it.
AB  - Sonography (ultrasound) is used routinely to assess an infant with nonbilious
      projectile emesis. Fluoroscopic upper gastrointestinal (UGI) series has been the
      standard method to evaluate infants with bilious emesis. We use sonographic UGI
      routinely to assess infants with nonbilious emesis as well as infants with
      bilious emesis. This essay illustrates our technique, the results obtained using
      this technique for normal anatomy, and the commonly encountered pathology.

PMID- 21966617
TI  - Diffusion-weighted Magnetic Resonance Imaging in the Early Diagnosis of Neonatal
      Adrenoleukodystrophy.
AB  - A newborn baby girl developed seizures right after birth. On the fourth day, the
      baby was examined using diffusion sequence magnetic resonance imaging (MRI) and
      diagnosed to have neonatal adrenoleukodystrophy. Laboratory findings confirmed
      the diagnosis. This is the first case of neonatal adrenoleukodystrophy (NALD)
      where diffusion MRI sequence helped in the diagnosis. We find association of NALD
      with seizures at birth is an extremely rare occurrence, and so far, only one case
      has been mentioned in the literature.

PMID- 21966618
TI  - Imaging of mechanical cardiac assist devices.
AB  - Diagnostic imaging plays an important role in the assessment of patients with
      mechanical cardiac assist devices. Therefore, it is important for radiologists to
      be familiar with the basic components, function, and radiographic appearances of
      these devices in order to appropriately diagnose complications. The purpose of
      this pictorial essay is to review indications, components, normal imaging
      appearances, and complications of surgically and percutaneously implanted
      ventricular assist devices, intra-aortic balloon pumps, and cardiac meshes.

PMID- 21966620
TI  - Ureteritis cystica: a radiologic pathologic correlation.
AB  - Ureteritis cystica (UC) is a benign condition that commonly affects the ureter
      and can mimic other conditions such as transitional cell carcinoma, blood clots,
      air bubbles, radiolucent stones, fibroepithelial polyps, and sloughed renal
      papillae. Radiographically, UC is characterized by multiple small, round, lucent
      defects, which cause scalloping of the ureteral margins when seen in profile. The
      scalloping is produced by the projection of the submucosal cysts into the lumen
      and represents an important differential feature of this disease. We present a
      case of UC with a radiological pathological correlation.

PMID- 21966619
TI  - Imaging of the bursae.
AB  - When assessing joints with various imaging modalities, it is important to focus
      on the extraarticular soft tissues that may clinically mimic joint pathology. One
      such extraarticular structure is the bursa. Bursitis can clinically be
      misdiagnosed as joint-, tendon- or muscle-related pain. Pathological processes
      are often a result of inflammation that is secondary to excessive local friction,
      infection, arthritides or direct trauma. It is therefore important to understand
      the anatomy and pathology of the common bursae in the appendicular skeleton. The
      purpose of this pictorial essay is to characterize the clinically relevant bursae
      in the appendicular skeleton using diagrams and corresponding multimodality
      images, focusing on normal anatomy and common pathological processes that affect
      them. The aim is to familiarize radiologists with the radiological features of
      bursitis.

PMID- 21966621
TI  - Photoacoustic imaging: opening new frontiers in medical imaging.
AB  - In today's world, technology is advancing at an exponential rate and medical
      imaging is no exception. During the last hundred years, the field of medical
      imaging has seen a tremendous technological growth with the invention of imaging
      modalities including but not limited to X-ray, ultrasound, computed tomography,
      magnetic resonance imaging, positron emission tomography, and single-photon
      emission computed tomography. These tools have led to better diagnosis and
      improved patient care. However, each of these modalities has its advantages as
      well as disadvantages and none of them can reveal all the information a physician
      would like to have. In the last decade, a new diagnostic technology called
      photoacoustic imaging has evolved which is moving rapidly from the research phase
      to the clinical trial phase. This article outlines the basics of photoacoustic
      imaging and describes our hands-on experience in developing a comprehensive
      photoacoustic imaging system to detect tissue abnormalities.

PMID- 21966622
TI  - The beginning.

PMID- 21966623
TI  - Bronchial Artery Aneurysm due to Pulmonary Tuberculosis: Detection with
      Multidetector Computed Tomographic Angiography.
AB  - A case of bronchial artery aneurysm due to pulmonary tuberculosis is reported.
      The patient presented with massive hemoptysis and the diagnosis was made using
      multidetector computed tomographic (MDCT) angiography. Selective bronchial
      arteriogram confirmed the MDCT findings and bronchial artery embolization was
      successfully performed with cessation of hemoptysis. Our article emphasizes the
      value of MDCT angiography in the diagnosis and management of such cases.

PMID- 21966624
TI  - Diffusion-weighted Magnetic Resonance Imaging: What Makes Water Run Fast or Slow?
AB  - Diffusion-Weighted Magnetic Resonance Imaging (DWI) obtains information useful in
      diagnosing several diseases through the measurement of random, Brownian diffusion
      of water molecules in tissues. This pictorial essay illustrates the main factors,
      i.e., ratio between the volume occupied by cells and the extracellular space,
      composition of the extracellular space, and temperature, that determine the rate
      of the water diffusion. The mechanism through which these influencing factors
      affect water diffusion is explained. Clinical and experimental examples, derived
      both from physiology and from non-human models, are described.

PMID- 21966625
TI  - Enforcing Quality Metrics over Equipment Utilization Rates as Means to Reduce
      Centers for Medicare and Medicaid Services Imaging Costs and Improve Quality of
      Care.
AB  - Radiology has been the focus of efforts to reduce inefficiencies while attempting
      to lower medical costs. The 2010 Medicare Physician Fee Schedule has reduced
      Centers for Medicare and Medicaid Services' (CMS) reimbursements related to the
      technical component of imaging services. By increasing the utilization rate, the
      cost of equipment spreads over more studies, thus lowering the payments per
      procedure. Is it beneficial for CMS to focus on equipment utilization as a cost
      cutting measure? Can greater financial and quality of care rewards be made by
      improving metrics like appropriateness criteria and pre-authorization?On
      examining quality metrics, such as appropriateness criteria and pre
      authorization, promising results have ensued. The development and enforcement of
      appropriateness criteria lowers overutilization of studies without requiring
      unattainable fixed rates. Pre-authorization educates ordering physicians as to
      when imaging is indicated.

PMID- 21966626
TI  - The fetal magnetic resonance imaging experience in a large community medical
      center.
AB  - Fetal magnetic resonance imaging (MRI) continues to prove a useful problem
      solving tool for diagnostic and management decision making issues encountered in
      the antenatal period. In this paper, we attempt to review basic fetal MRI
      protocol considerations and demonstrate key imaging findings through multiple
      modalities, with pathologic correlation in several cases. A study of five fetal
      MRI cases, from our institution, were selected in order to highlight both the
      indications for, and benefits obtained from this advanced imaging technique.
      Fetal MRI proved useful in each case in better defining fetal anomalies,
      especially where ultrasound (due to drawbacks such as shadowing by pelvic bones)
      was unable to be completely diagnostic. The more in-depth study made possible by
      MRI also helped with formulation of disease prognosis and estimation of survival
      chances of the fetus. Further, MRI as a diagnostic and prognostic tool has become
      more ubiquitous across the medical community. This imparts tangible benefit to
      patients, who are now able to find this service within arm's reach. Whereas
      previously these patients were obligatorily referred up to 90 miles away from our
      centre for further medical work-up, now a large percentage can obtain their
      prenatal imaging and perinatal care locally. In addition, medical education
      benefits as new types of cases, those with pathology of the antenatal period, are
      retained for work-up and management in these large community settings. Cases from
      our institution exemplify these types of pathologies, from fetal chest masses to
      a syndromic presentation of bilateral renal agenesis.

PMID- 21966627
TI  - Imaging-guided Parenchymal Liver Biopsy: How We Do It.
AB  - Liver biopsies are performed for both focal and nonfocal lesions (parenchymal).
      In our center, majority of liver biopsies are performed for parenchymal liver
      disease. Parenchymal liver biopsy plays a key role in the diagnosis of various
      diffuse liver dysfunctions. Results of the biopsy help grade the disease,
      facilitating prognostication, which helps in planning specific treatment
      strategies. Imaging guidance is gaining wide acceptance as the standard
      procedure. Ultrasound (US) guidance is currently considered the most cost
      effective and safe way to perform parenchymal liver biopsies. Radiologists
      worldwide and particularly in the United States are increasingly performing this
      procedure. Radiologists performing biopsies generally use the cutting needle.
      Different needle sizes, techniques and preference for biopsy of the right or left
      lobe have been described. We attribute these preferences to prior training and
      individual radiologist's comfort level. We describe the algorithm followed at our
      institution for performing percutaneous US-guided parenchymal liver biopsy. While
      clinical societies have recommended a minimum of 40 liver biopsies as a
      requirement for proficiency of clinicians, specific to radiology trainees/fellows
      interested in pursuing a career in intervention, we feel a total of 20 liver
      biopsies (includes assisted and independently performed biopsies under
      supervision) should be adequate training.

PMID- 21966628
TI  - Image-guided Percutaneous Drainage in the Pediatric Population: A Primer for
      Radiologists.
AB  - Image-guided percutaneous drainage is an excellent minimally invasive method for
      dealing with infectious complications in the pediatric population. A thorough
      understanding of drainage procedures in children can often lead to improved
      patient outcomes. Indications for percutaneous drainage will be reviewed,
      including abscesses related to appendicitis, post-surgical abscess formation, and
      abscesses related to Crohn's disease. This pictorial essay will help the
      radiologist better understand the common etiologies of abscesses in children that
      may require percutaneous drainage, the special considerations for catheter
      placement, patient preparation, and anesthesia or sedation issues unique to the
      pediatric population.

PMID- 21966629
TI  - Imaging features of the pleuropulmonary manifestations of rheumatoid arthritis:
      pearls and pitfalls.
AB  - Rheumatoid arthritis (RA) is a common disorder that affects the joints. RA is a
      systemic disease associated with relatively frequent and variable pleuropulmonary
      manifestations. This article reviews the common and potentially serious thoracic
      sequelae in terms of pleural disease, pulmonary nodules, airways disorders, and
      interstitial disease, as well as pulmonary side effects of antirheumatic
      medication. An imaging-guided approach to classification of RA-associated lung
      disease is outlined and the comparative values of different imaging modalities
      are discussed. An appreciation of current knowledge of epidemiology, pathological
      correlation, and prognostic implications of different RA-associated lung disease
      is provided. We highlight importance of considering pertinent differential
      diagnoses to avoid misdiagnosis, and outline common pitfalls in dealing with
      pleuropulmonary rheumatoid disease.

PMID- 21966630
TI  - Communicating tubular duplication of upper esophagus-a rare occurrence.
AB  - Duplications of esophagus are commonly classified into two types, tubular and
      cystic. Tubular duplication of esophagus is a rare occurrence and is much less
      common than cystic duplication of foregut. Most esophageal duplications are
      located in the lower third of the esophagus. A cervical esophageal duplication is
      extremely rare. Esophageal duplications have been reported twice as commonly on
      the right as on the left. We report a case of incidental finding identified on
      computed tomography of communicating tubular esophageal duplication involving the
      left side of the upper esophagus in a tuberculosis patient that was subsequently
      confirmed on barium swallow test.

PMID- 21966631
TI  - Sonographic findings of additional malignant lesions in breast carcinoma seen by
      second look ultrasound.
AB  - OBJECTIVE: The aim is to show ultrasound (US) findings of additional malignant
      lesions of breast carcinoma visualized on targeted second-look US that were not
      identified by mammography or US prior to the time of diagnosis. MATERIALS AND
      METHODS: A double-blind retrospective review of the US results from January 2008
      through August 2010 of 228 patients with known breast cancer was conducted by two
      expert radiologists. The focus of the review was on the second-look US
      characteristics (following BI-RADS criteria) of 26 documented additional
      malignant lesions of the 76 with successful sonographic correlation from the 123
      lesions detected by magnetic resonance imaging (MRI). All of them, before the
      MRI, had an initial mammography and a US with a histopathological biopsy of the
      primary lesion. RESULTS: Approximately 60 to 70% of the findings were classified
      as BI-RADS 2 and BI-RADS 3, while assessing the final US category. The review of
      the second-look US showed the size of the second malignant additional lesion
      ranged from 3 to 22 mm, of which 90% were smaller than 10 mm and 66% were smaller
      than 7 mm. CONCLUSIONS: Most additional malignant lesions, nonpalpable
      carcinomas, which were previously not detected by mammography and US at first
      look diagnosis, were detected by a targeted second-look US examination. These
      lesions were of category BI-RADS 2 and BI-RADS 3 and smaller than 7 mm.

PMID- 21966633
TI  - A very rapid visual recovery of posterior reversible encephalopathy syndrome.

PMID- 21966632
TI  - Role of Magnetic Resonance Enterography in Differentiating between Fibrotic and
      Active Inflammatory Small Bowel Stenosis in Patients with Crohn's Disease.
AB  - OBJECTIVE: To assess the diagnostic accuracy of magnetic resonance imaging (MRI)
      in prospectively differentiating between fibrotic and active inflammatory small
      bowel stenosis in patients with Crohn's disease (CD). MATERIALS AND METHODS: A
      total of 111 patients with histologically proven CD presenting with clinical and
      plain radiographic signs of small bowel obstruction underwent coronal and axial
      MRI scans after oral administration of polyethylene glycol solution. A stenosis
      was judged present if a small bowel segment had >80% lumen reduction as compared
      to an adjacent normal loop and mural thickening of >3 mm. At the level of the
      stenosis, both T2 signal intensity and post-gadolinium T1 enhancement were
      quantified using a 5-point scale (0: very low; 1: low; 2: moderate; 3: high; and
      4: very high). A stenosis was considered fibrotic if the sum of the two values
      (activity score: AS) did not exceed 1. RESULTS: A small bowel stenosis was
      identified in 48 out of 111 patients. Fibrosis was confirmed at histology in all
      of the 23 patients with AS of 0 or 1, who underwent surgery within 3 days of the
      MRI examination. In the remaining 25 patients (AS: 2-8), an active inflammatory
      stenosis was suspected and remission of the obstructive symptoms was obtained by
      means of medical treatment. One of these patients (AS: 2), however, underwent
      surgery after 14 days, due to recurrence. MRI had 95.8% sensitivity, 100%
      specificity, and 97.9% accuracy in the diagnosis of fibrotic stenosis.
      CONCLUSION: MRI is reliable in differentiating fibrotic from inflammatory small
      bowel stenosis in CD.

PMID- 21966634
TI  - Crohn's disease: Multimodality Imaging of Surgical Indications, Operative
      Procedures, and Complications.
AB  - Surgical management is considered for specific indications in Crohn's disease and
      a wide variety of surgeries is performed. The purpose of this pictorial essay is
      to depict manifestations of Crohn's disease that indicates surgery, various
      surgical procedures that are performed, and the complications arising from these
      surgical procedures. Surgical indications including obstruction due to strictures
      or adhesions, fistulae and abscesses, and surgeries for these conditions, such
      as, ileocecectomy, stricturoplasty, small bowel resection, fecal diversion,
      segmental colectomy, and lysis of adhesions and their complications will be
      discussed and their imaging will also be illustrated.

PMID- 21966636
TI  - The forgotten guide wire: a rare complication of hemodialysis catheter insertion.
AB  - A rare complication of a hemodialysis catheter insertion is the loss of the
      complete guide wire into the circulation. A complete guide wire in the
      circulation may not necessarily produce symptoms, and it may remain unnoticed for
      a significant period of time. We present a rare case where a complete guide wire
      was lost into the circulation during insertion of a hemodialysis catheter into
      the right femoral vein in a 19-year-old female with systemic lupus
      erythromatosis. The patient remained asymptomatic through two plasmapheresis
      treatments over a period of 2 days. The guide wire was eventually retrieved
      without complications. The factors leading to the wire being forgotten will be
      reviewed, and the measures initiated to prevent any future occurrence will be
      addressed.

PMID- 21966635
TI  - Clinically relevant imaging in tuberous sclerosis.
AB  - Tuberous sclerosis (TS), also known as Bourneville disease or Bourneville-Pringle
      disease, is an autosomal dominant genetic disorder classically characterized by
      the presence of hamartomatous growths in multiple organs. TS and tuberous
      sclerosis complex (TSC) are different terms for the same genetic condition. Both
      terms describe clinical changes due to mutations involving either of the two
      genes named TSC1 and TSC2, which regulate cell growth. The diagnosis of TSC is
      established using diagnostic criteria based on clinical and imaging findings.
      Routine screening and surveillance of patients with TSC is needed to determine
      the presence and extent of organ involvement, especially the brain, kidneys, and
      lungs, and identify the development of associated complications. As the treatment
      is organ specific, imaging plays a crucial role in the management of patients
      with TSC.

PMID- 21966637
TI  - High-throughput assessment of bacterial growth inhibition by optical density
      measurements.
AB  - The increasing incidence of antibiotic-resistant bacterial infections both in
      hospitals and in the community intensifies the need for new antibacterial
      strategies and targets. Although high-throughput screening against live bacteria
      allows rapid discovery of compounds with growth-inhibitory activities, these
      efforts have failed to fill the pipeline with the anticipated antibacterial
      compounds because target identification is often onerous. Recently, a strategy
      was reported that employs a bacteria growth inhibition assay readout using
      optical density measurements on paired strains - both a wildtype strain and a
      pathway-null mutant - to find inhibitors of wildtype bacterial growth that
      specifically target conditionally essential enzymes in the pathway of interest.
      Protocols are provided here for determining the robustness of an assay, screening
      in a high-throughput format and setting up dose-response curves in paired
      Staphylococcus aureus strains. However, the protocols can be used to screen for
      growth-inhibitory compounds in any bacterial strain of interest.

PMID- 21966638
TI  - Breakthrough in cachexia treatment through a novel selective androgen receptor
      modulator?!
AB  - Cachexia, and particularly the loss of metabolically active lean tissue, leads to
      increased morbidity and mortality in affected patients. An impairment of strength
      and functional status is usually associated with cachexia. A variety of anabolic
      and appetite-stimulating agents have been studied in patients with cachexia
      caused by various underlying diseases. Overall, these studies have demonstrated
      that treatment can increase body weight and/or lean body mass. However, these
      therapies may have severe side effects, particularly when utilizing testosterone
      and related anabolic steroids targeting the androgen receptor. These side effects
      include cardiovascular problems, prostate hyperplasia and cancer in men, as well
      as virilization in women.

PMID- 21966639
TI  - The epidemiology of sarcopenia in community living older adults: what role does
      lifestyle play?
AB  - BACKGROUND: Sarcopenia, the age-related decline in skeletal muscle mass and
      function, is a relatively poorly understood process which may play an important
      role in the incidence of physical disability and falls in older adults. Evidence
      demonstrates that both genetic and environmental factors contribute to increased
      susceptibility for sarcopenia development, yet some of these factors may
      represent unavoidable consequences of ageing.  METHODS: A review of literature,
      generally from epidemiological research, was performed to examine the influence
      that potentially modifiable lifestyle factors (general physical activity, dietary
      nutrient intake and sun exposure), as well as chronic disease and medication use,
      may have on sarcopenia progression.  RESULTS: The review demonstrated that while
      physical activity, nutrient intake and sun exposure often decline during ageing,
      each may have important but differing benefits for the prevention of muscle mass
      and functional declines in older adults. Conversely, age-related increases in the
      prevalence of chronic diseases and the subsequent prescription of pharmacotherapy
      may exacerbate sarcopenia progression.  CONCLUSIONS: The prevalence of poor
      physical activity, diet and sun exposure, as well as chronic disease and
      medication use, within older adult populations may be modifiable through simple
      lifestyle and health care interventions. As such, these factors may represent the
      most effective targets for sarcopenia prevention during the ageing process.

PMID- 21966640
TI  - Cardio-renal cachexia syndromes (CRCS): pathophysiological foundations of a
      vicious pathological circle.
AB  - Cardio-renal syndromes (CRS) are defined as disorders of the heart and kidney
      whereby acute or chronic dysfunction in one organ may induce acute or chronic
      dysfunction of the other. CRS have been classified into five categories, where
      types 2 and 4 represent respectively chronic cardio-renal and chronic reno
      cardiac syndromes. In these conditions, the chronic disorder of either the heart
      or kidney has been shown to induce some degree of cachexia. At the same time,
      cachexia has been proposed as a possible mechanism contributing to the worsening
      of such pathological organ cross talk. Common pathogenetic mechanisms underlie
      body wasting in cachectic states of different chronic heart and kidney diseases.
      In these circumstances, a vicious circle could arise, in which cachexia
      associated with either heart failure or chronic kidney disease may contribute to
      further damage of the other organ. In chronic CRS, activation of the immune and
      neuroendocrine systems contributes to the genesis of cachexia, which in turn can
      negatively affect the heart and kidney function. In patients with cardiac
      sustained activation of the immune and neuroendocrine systems and oxidative
      stress, renal vascular resistance can increase and therefore impair renal
      perfusion, leading to worsening kidney function. Similarly, in renal cachexia,
      increased levels of pro-inflammatory cytokines can cause progressive left
      ventricular systolic dysfunction, myocardial cell death, endothelial dysfunction
      and increased myocardial fibrosis, with consequent impairment of the chronic reno
      cardiac syndrome type 4. Thus, we speculate that the occurrence of different
      types of chronic CRS could represent a fundamental step in the genesis of
      cachexia, being renal and cardiac dysfunction closely related to the occurrence
      of systemic disorders leading to a final common pathway. Therefore, the heart and
      kidney and cachexia represent a triad causing a vicious circle that increases
      mortality and morbidity: In such circumstances, we may plausibly talk about
      cardio-renal cachexia syndrome. Complex interrelations may explain the transition
      from CRS to cachexia and from cachexia to CRS. Identification of the exact
      mechanisms occurring in these conditions could potentially help in preventing and
      treating this deadly combination.

PMID- 21966642
TI  - The orally active melanocortin-4 receptor antagonist BL-6020/979: a promising
      candidate for the treatment of cancer cachexia.
AB  - BACKGROUND: Under physiological conditions, the melanocortin system is a crucial
      part of the complex network regulating food intake and energy expenditure. In
      pathological states, like cachexia, these two parameters are deregulated, i.e.,
      food intake is decreased and energy expenditure is increased-a vicious
      combination leading to catabolism. Agouti-related protein (AgRP), the endogenous
      antagonist at the melanocortin-4 receptor (MC-4R), was found to increase food
      intake and to reduce energy expenditure. This qualifies MC-4R blockade as an
      attractive mode of action for the treatment of cachexia. Based on this rationale,
      a novel series of small-molecule MC-4R antagonists was designed, from which the
      orally active compound BL-6020/979 (formerly known as SNT207979) emerged as the
      first promising development candidate showing encouraging pre-clinical efficacy
      and safety properties which are presented here.  METHODS AND RESULTS: BL-6020/979
      is an orally available, selective and potent MC-4R antagonist with a drug-like
      profile. It increased food intake and decreased energy expenditure in healthy
      wild-type but not in MC-4R deficient mice. More importantly, it ameliorated
      cachexia-like symptoms in the murine C26 adenocarcinoma model; with an effect on
      body mass and body composition and on the expression of catabolic genes.
      Moreover, BL-6020/979 showed antidepressant-like properties in the chronic mild
      stress model in rats and exhibits a favorable safety profile.  CONCLUSION: The
      properties of BL-6020/979 demonstrated in animal models and presented here make
      it a promising candidate suitable for further development towards a first-in
      class treatment option for cachexia that potentially opens up the opportunity to
      treat two hallmarks of the disease, i.e., decreased food intake and increased
      energy expenditure, with one drug.

PMID- 21966641
TI  - The role of myostatin in muscle wasting: an overview.
AB  - Myostatin is an extracellular cytokine mostly expressed in skeletal muscles and
      known to play a crucial role in the negative regulation of muscle mass. Upon the
      binding to activin type IIB receptor, myostatin can initiate several different
      signalling cascades resulting in the upregulation of the atrogenes and
      downregulation of the important for myogenesis genes. Muscle size is regulated
      via a complex interplay of myostatin signalling with the insulin-like growth
      factor 1/phosphatidylinositol 3-kinase/Akt pathway responsible for increase in
      protein synthesis in muscle. Therefore, the regulation of muscle weight is a
      process in which myostatin plays a central role but the mechanism of its action
      and signalling cascades are not fully understood. Myostatin upregulation was
      observed in the pathogenesis of muscle wasting during cachexia associated with
      different diseases (i.e. cancer, heart failure, HIV). Characterisation of
      myostatin signalling is therefore a perspective direction in the treatment
      development for cachexia. The current review covers the present knowledge about
      myostatin signalling pathways leading to muscle wasting and the state of therapy
      approaches via the regulation of myostatin and/or its downstream targets in
      cachexia.

PMID- 21966643
TI  - Increased desmin expression in hindlimb muscles of aging rats.
AB  - BACKGROUND: Aging skeletal muscle frequently exhibits a reduction in force
      produced per unit muscle tissue, variously termed muscle quality, specific
      tension or dynapenia. Muscles from animals in which desmin expression is reduced
      exhibit similar properties, raising the possibility that reduced desmin
      expression contributes to impaired force production in aging muscles.  METHODS:
      We examined expression of desmin and synemin, both intermediate filament
      proteins, in the plantarflexor muscles of adult (6-8 months) and older (24
      months) rats. We have previously reported age-related reductions in muscle
      quality and sarcoplasmic reticulum function in these animals.  RESULTS:
      Significant effects of age and muscle were found for the expression of desmin (P
      = 0.040 and <0.001 respectively), but not synemin. Desmin expression was
      increased in the aging muscles, with the greatest changes observed in the
      gastrocnemius muscles. Muscle quality, but not muscle mass, was reduced in the
      aging plantarflexor muscles.  CONCLUSIONS: Loss of desmin does not account for
      reduced force production in aging muscles. The potential effects of the age
      related increase in desmin on muscle function remain unclear, but may include
      dissipation of contractile force.

PMID- 21966644
TI  - Decreased NADPH oxidase expression and antioxidant activity in cachectic skeletal
      muscle.
AB  - BACKGROUND: Cancer cachexia is the progressive loss of skeletal muscle protein
      that contributes significantly to cancer morbidity and mortality. Evidence of
      antioxidant attenuation and the presence of oxidised proteins in patients with
      cancer cachexia indicate a role for oxidative stress. The level of oxidative
      stress in tissues is determined by an imbalance between reactive oxygen species
      production and antioxidant activity. This study aimed to investigate the
      superoxide generating NADPH oxidase (NOX) enzyme and antioxidant enzyme systems
      in murine adenocarcinoma tumour-bearing cachectic mice.  METHODS: Superoxide
      levels, mRNA levels of NOX enzyme subunits and the antioxidant enzymes superoxide
      dismutase (SOD), glutathione peroxidise (GPx) and catalase was measured in the
      skeletal muscle of mice with cancer and cancer cachexia. Protein expression
      levels of NOX enzyme subunits and antioxidant enzyme activity was also measured
      in the same muscle samples.  RESULTS: Superoxide levels increased 1.4-fold in the
      muscle of mice with cancer cachexia, and this was associated with a decrease in
      mRNA of NOX enzyme subunits, NOX2, p40(phox) and p67(phox) along with the
      antioxidant enzymes SOD1, SOD2 and GPx. Cancer cachexia was also associated with
      a 1.3-fold decrease in SOD1 and 2.0-fold decrease in GPx enzyme activity. 
      CONCLUSION: Despite increased superoxide levels in cachectic skeletal muscle, NOX
      enzyme subunits, NOX2, p40(phox) and p67(phox), were downregulated along with the
      expression and activity of the antioxidant enzymes. Therefore, the increased
      superoxide levels in cachectic skeletal muscle may be attributed to the reduction
      in the activity of endogenous antioxidant enzymes.

PMID- 21966645
TI  - Thyroid disorders and bone mineral metabolism.
AB  - Thyroid diseases have widespread systemic manifestations including their effect
      on bone metabolism. On one hand, the effects of thyrotoxicosis including
      subclinical disease have received wide attention from researchers over the last
      century as it an important cause of secondary osteoporosis. On the other hand,
      hypothyroidism has received lesser attention as its effect on bone mineral
      metabolism is minimal. Therefore, this review will primarily focus on
      thyrotoxicosis and its impact on bone mineral metabolism.

PMID- 21966646
TI  - Oral manifestations of thyroid disorders and its management.
AB  - The thyroid is the major regulator of metabolism and affects all of the bodily
      functions. Thyroid dysfunction is the second most common glandular disorder of
      the endocrine system which may rear its head in any system in the body including
      the mouth. The oral cavity is adversely affected by either an excess or
      deficiency of these hormones. Before treating a patient who has thyroid disorder,
      the endocrinologist needs to be familiar with the oral manifestations of thyroid
      dysfunctions. The patient with a thyroid dysfunction, as well as the patient
      taking medications for it, requires proper risk management before considering
      dental treatment by the dentist. Thus, communication of dentist with
      endocrinologist must be bidirectional, to maintain patient's oral and thyroid
      health.

PMID- 21966647
TI  - Transient congenital hypothyroidism.
AB  - Transient thyroid function abnormalities in the new born which revert back to
      normal after varying periods of time are mostly identified in the neonatal
      screening tests for thyroid and are becoming more common because of the survival
      of many more premature infants. It can be due to factors primarily affecting the
      thyroid-like iodine deficiency or excess, maternal thyroid-stimulating hormone
      receptor (TSHR) antibodies, maternal use of antithyroid drugs, DUOX 2 (dual
      oxidase 2) mutations, and prematurity or those that affect the pituitary-like
      untreated maternal hyperthyroidism, prematurity, and drugs. Most of these require
      only observation, whereas some, such as those due to maternal TSHR antibodies may
      last for upto three-to-six months and may necessitate treatment. Isolated
      hyperthyrotropinemia (normal Tetraiodothyronine (T4) and high Thyroid Stimulating
      hormone (TSH)) may persist as subclinical hypothyroidism in childhood. Transient
      hypothyroxinemia (low T4 and normal TSH) is very common in premature babies. The
      recognition of these conditions will obviate the risks associated with
      unnecessary thyroxine supplementation in childhood and parental concerns of a
      life long illness in their offspring.

PMID- 21966648
TI  - Thyroidology over the ages.
AB  - Thyroidolody, the study of the thyroid gland, is considered to be a relatively
      new field of endocrinology. However, references to the thyroid gland and its
      diseases can be seen in the literature of ancient Greek, Indian and Egyptian
      medicine. Goiter has always been a disease of immense interest of the general
      population due to its widespread prevalence. It is one of the most common medical
      problems portrayed in ancient paintings. Owing to the lack of awareness and poor
      nutritious habits of the people in that era, diseases such as iodine deficiency
      goiter were common. Physicians, healers and philosophers had been attempting time
      and again until the 19(th) century to come up with explanations of the thyroid
      gland and provide a reasonable basis of its diseases. Although the discovery of
      thyroid gland, its structure, function and diseases has been accredited to modern
      scientists who presented their work mostly in the 19(th) and 20(th) century, it
      is of significance to note that much of what we discovered in the 19(th) and
      20(th) century had already been known centuries ago. This review attempts to
      explain the knowledge of thyroid gland, its function and diseases as held by the
      people in the previous centuries; and how this knowledge evolved over the years
      to become what it is today.

PMID- 21966649
TI  - Prevalence of upper airway obstruction in patients with apparently asymptomatic
      euthyroid multi nodular goitre.
AB  - AIMS: To study the prevalence of upper airway obstruction (UAO) in "apparently
      asymptomatic" patients with euthyroid multinodular goitre (MNG) and find
      correlation between clinical features, UAO on pulmonary function test (PFT) and
      tracheal narrowing on computerised tomography (CT). MATERIALS AND METHODS:
      Consecutive patients with apparently asymptomatic euthyroid MNG attending thyroid
      clinic in a tertiary centre underwent clinical examination to elicit features of
      UAO, PFT, and CT of neck and chest. STATISTICAL ANALYSIS USED: Statistical
      analysis was done with SPSS version 11.5 using paired t-test, Chi square test,
      and Fisher's exact test. P value of <0.05 was considered to be significant.
      RESULTS: Fifty-six patients (52 females and four males) were studied. The
      prevalence of UAO (PFT) and significant tracheal narrowing (CT) was 14.3%. and
      9.3%, respectively. Clinical features failed to predict UAO or significant
      tracheal narrowing. Tracheal narrowing (CT) did not correlate with UAO (PFT).
      Volume of goitre significantly correlated with degree of tracheal narrowing.
      CONCLUSIONS: Clinical features do not predict UAO on PFT or tracheal narrowing on
      CT in apparently asymptomatic patients with euthyroid MNG.

PMID- 21966650
TI  - Accuracy of ultrasound-guided fine-needle aspiration cytology for diagnosis of
      carcinoma in patients with multinodular goiter.
AB  - BACKGROUND: Fine-needle aspiration (FNA) is a useful method for evaluating
      multinodular goiter; however, its role is still controversial. The aim of this
      study was to assess the utility of ultrasound-guided thyroid FNA in detecting
      malignancy in patients with multinodular goiter in Oman. MATERIALS AND METHODS:
      This was a retrospective study where all patients with multinodular goiter seen
      at the Sultan Qaboos University Hospital endocrinology clinic in Oman in 2005
      were evaluated. The thyroid FNA results were grouped into either malignancy
      (positive result) or others (negative result). They were compared to those of
      final histopathological examination in order to calculate the value of the test
      in diagnosing malignancy. Analyses were evaluated using descriptive statistics.
      RESULTS: A total of 272 patients were included in the study. The mean age was
      39?13 years with an age range from 5 to 85 years. The majority of the patients
      were females (n=236; 87%). The results of thyroid FNA revealed that 6% (n=15) of
      the patients had malignancies while histopathological results showed that the
      proportion of subjects with malignancies was 18% (n=49). Out of the 15 cases
      identified to have malignances by thyroid FNA, only 53% (n=8) of the subjects
      were confirmed to have malignancy by biopsy. Overall, the results of the tests
      were poor, revealing a sensitivity of 16%, specificity of 97% and a diagnostic
      accuracy of 82%, with a positive predictive value of 53% and a negative
      predictive value of 84%. CONCLUSION: Thyroid FNA is not a useful test in
      differentiating multinodular goiter from malignancy, as more than 80% of the
      malignancies go unnoticed.

PMID- 21966651
TI  - A 64 year-old female with scalp metastasis of papillary thyroid cancer.
AB  - The skin metastasis of papillary thyroid carcinoma (PTC) is a rare condition and
      the lesions should be differentiated from primary skin tumors. The scalp is the
      most frequent site which is involved in skin metastasis of PTC. It shows the poor
      outcome and aggressive nature of disease. In this report, we aim to present a
      case report of a 64 year-old female with scalp metastasis of PTC in the context
      of disseminated pulmonary and liver metastasis.

PMID- 21966652
TI  - Elevated thyroid stimulating hormone in a neonate: Drug induced or disease?
AB  - Dyshormonogenesis is an uncommon cause of congenital hypothyroidism. The most
      common abnormality is absent or insufficient thyroid peroxidase enzyme. Maternal
      intake of antithyroid drug can also lead to elevated thyroid stimulating hormone
      (TSH) in a neonate, albeit the scenario is temporary. We report one such
      interesting case where a clinically euthyroid neonate borne to a mother on
      antithyroid drug presents on 12(th) day of life with reports of elevated TSH and
      increased tracer uptake in 99mTc thyroid scan. Disproportionately high TSH in
      comparison to low maternal antithyroid drug dosage and further elevation of TSH
      after stopping mother's antithyroid drugs ruled out maternal antithyroid drug
      induced congenital hypothyroidism in the baby. Early institution of therapy in
      these patients can prevent mental retardation and other features of
      hypothyroidism.

PMID- 21966653
TI  - An unusual presentation of a usual disorder: Van Wyk-Grumbach syndrome.
AB  - Van Wyk-Grumbach syndrome (VWGS) is characterized by juvenile hypothyroidism,
      delayed bone age, and isosexual precocious puberty. A 10.7-year-old girl
      presented with premature menarche and isosexual precocity. She had delayed bone
      age and multicystic ovaries. High circulating levels of TSH with prepubertal LH
      confirmed the diagnosis of VWGS. Tendency to manifest sexual precocity in VWGS
      may be directly related to the severity of the TSH elevation. High circulating
      levels of TSH acting directly on FSH receptors are the actual mediators of
      precocity.

PMID- 21966654
TI  - Cardiac tamponade in a patient with primary hypothyroidism.
AB  - Pericardial effusion is frequently found in patients with hypothyroidism, but it
      is rarely associated with cardiac tamponade. Hypothyroidism complicated by
      cardiac tamponade is rarely referenced in the medical literature. Here we report
      an unusual case of a 45-year-old female, who presented with breathlessness and
      was found to have hypothyroidism with large pericardial effusion with cardiac
      tamponade. Treatment included an emergency pericardiocentesis followed by
      thyroxine hormone replacement.

PMID- 21966655
TI  - Thyrotoxic periodic paralysis.
AB  - This article aims at highlighting the importance of suspecting thyrotoxicosis in
      cases of recurrent periodic flaccid paralysis; especially in Asian men to
      facilitate early diagnosis of the former condition. A case report of a 28 year
      old male patient with recurrent periodic flaccid paralysis has been presented.
      Hypokalemia secondary to thyrotoxicosis was diagnosed as the cause of the
      paralysis. The patient was given oral potassium intervention over 24 hours. The
      patient showed complete recovery after the medical intervention and was
      discharged after 24 hours with no residual paralysis. Thyrotoxic periodic
      paralysis (TPP) is a complication of thyrotoxicosis, more common amongst males in
      Asia. It presents as acute flaccid paralysis in a case of hyperthyroidism with
      associated hypokalemia. The features of thyrotoxicosis may be subtle or absent.
      Thus, in cases of recurrent or acute flaccid muscle paralysis, it is important to
      consider thyrotoxicosis as one of the possible causes, and take measures
      accordingly.

PMID- 21966656
TI  - Thyroidology and public health: The challenges ahead.

PMID- 21966657
TI  - Ensuring an intelligent India: Managing hypothyroidism in pregnancy.

PMID- 21966658
TI  - Thyroid disorders in India: An epidemiological perspective.
AB  - Thyroid diseases are common worldwide. In India too, there is a significant
      burden of thyroid diseases. According to a projection from various studies on
      thyroid disease, it has been estimated that about 42 million people in India
      suffer from thyroid diseases. This review will focus on the epidemiology of five
      common thyroid diseases in India: (1) hypothyroidism, (2) hyperthyroidism, (3)
      goiter and iodine deficiency disorders, (4) Hashimoto's thyroiditis, and (5)
      thyroid cancer. This review will also briefly cover the exciting work that is in
      progress to ascertain the normal reference range of thyroid hormones in India,
      especially in pregnancy and children.

PMID- 21966659
TI  - Epidemiology of thyroid diseases in Africa.
AB  - BACKGROUND: Thyroid disorders are common endocrine disorders encountered in the
      African continent. Environmental and nutritional factors are often implicated in
      the occurrence of some thyroid disorders that occur in this part of the world.
      This is a narrative review that seeks to document the pattern, prevalence, and
      management of thyroid disorders in the continent. MATERIALS AND METHODS: The
      search engine used for this review were PubMed and Google scholar. All available
      articles on thyroid disorders from the sub-African continent, published until May
      2011, were included. RESULTS: Iodine deficiency disorders (IDD) which top the
      list of thyroid disorders and remain the commonest cause of thyroid disorders in
      the continent is often affected not only by the iodine status in the region but
      sometimes also by selenium deficiency and thiocyanate toxicity. The reported
      prevalence rates of endemic goiter range from 1% to 90% depending on the area of
      study with myxedematous cretinism still a prominent feature of IDD in only a few
      regions of the continent. The extent of autoimmune thyroid disorders remains
      unknown because of underdiagnosis and underreporting but the few available
      studies note a prevalence rate of 1.2% to 9.9% of which Graves diseases is the
      commonest of these groups of disorders. Rarer causes of thyroid dysfunction such
      as thyroid tuberculosis and amiodarone related causes are also documented in this
      review. The onset of new thyroid diseases following amiodarone usage was
      documented in 27.6% of persons treated for arrhythmia. Reports on thyroid
      malignancies (CA) in Africa abound and differentiated thyroid malignancies are
      noted to occur more commonly than the other forms of thyroid CA. The documented
      prevalence rates of thyroid CA in the African continent are as follows
      (papillary: 6.7-72.1%, follicular: 4.9-68%, anaplastic: 5-21.4%, and medullary:
      2.6%-13.8%). For the differentiated thyroid CA, there is a changing trend toward
      the more frequent occurrence of papillary CA compared to follicular CA and this
      may be attributable to widespread iodization programs. Our review shows that
      diagnosis and evaluation of thyroid disorders are reliant in most regions of the
      continent on clinical acumen and suboptimal diagnostic facilities and expertise
      are what obtain in many practices. The frequently employed management options of
      thyroid disorders in the continent are pharmacological and surgical treatment
      modalities. CONCLUSION: Diagnosis and management of thyroid disorders in the
      African continent remain suboptimal. Thyroid registries may be helpful to
      determine the scope of the burden of thyroid disorders since this knowledge may
      help change policies on the approach to the management of these disorders.

PMID- 21966660
TI  - Clinical scoring scales in thyroidology: A compendium.
AB  - This compendium brings together traditional as well as contemporary scoring and
      grading systems used for the screening and diagnosis of various thyroid diseases,
      dysfunctions, and complications. The article discusses scores used to help
      diagnose hypo-and hyperthyroidism, to grade and manage goiter and ophthalmopathy,
      and to assess the risk of thyroid malignancy.

PMID- 21966661
TI  - Why are our hypothyroid patients unhappy? Is tissue hypothyroidism the answer?
AB  - A large number of hypothyroid patients, receiving adequate doses of thyroxine
      supplementation, continue to complain of dissatisfaction and varied symptoms.
      This review discuses the concept of tissue hypothyroidism and suggests methods of
      measuring it, while calling for improvements in the medical management of
      hypothyroidism.

PMID- 21966667
TI  - Microfluidic waves.
AB  - The propagation of pressure waves in fluidic channels with elastic covers is
      discussed in view of applications to flow control in microfluidic devices. A
      theory is presented which describes pressure waves in the fluid that are coupled
      to bending waves in the elastic cover. At low frequencies, the lateral bending of
      the cover dominates over longitudinal bending, leading to propagating, non
      dispersive longitudinal pressure waves in the channel. The theory addresses
      effects due to both the finite viscosity and compressibility of the fluid. The
      coupled waves propagate without dispersion, as long as the wave length is larger
      than the channel width. It is shown that in channels of typical microfluidic
      dimensions, wave velocities in the range of a few 10 m s(-1) result if the
      channels are covered by films of a compliant material such as PDMS. The
      application of this principle to design microfluidic band pass filters based on
      standing waves is discussed. Characteristic frequencies in the range of a few kHz
      are readily achieved with quality factors above 30.

PMID- 21966668
TI  - A new ion-exchange adsorbent with paramagnetic properties for the separation of
      genomic DNA.
AB  - A new ion-exchange adsorbent (IEA) derived from Fe(3)O(4)/SiO(2)-GPTMS-DEAE with
      paramagnetic properties was prepared. Fe(3)O(4) nanoparticles were firstly
      prepared in water-in-oil microemulsion. The magnetic Fe(3)O(4) particles were
      modified in situ by hydrolysis and condensation reactions with tetraethoxysilane
      (TEOS) to form the core-shell Fe(3)O(4)/SiO(2). The modified particles were
      further treated by 3-glycidoxypropyltrimethoxysilane (GPTMS) to form
      Fe(3)O(4)/SiO(2)-GPTMS nanoparticles. Fe(3)O(4)/SiO(2)-GPTMS-DEAE nanoparticles
      (IEA) were finally obtained through the condensation reaction between the Cl of
      diethylaminoethyl chloride-HCl (DEAE) and the epoxy groups of GPTMS in the
      Fe(3)O(4)/SiO(2)-GPTMS. The obtained IEA has features of paramagnetic and ion
      exchange properties because of the Fe(3)O(4) nanoparticles and protonated organic
      amine in the sample. The intermediates and final product obtained in the
      synthesis process were characterized. The separation result of genomic DNA from
      blood indicated that Fe(3)O(4)/SiO(2)-GPTMS-DEAE nanoparticles have outstanding
      advantages in operation, selectivity, and capacity.

PMID- 21966662
TI  - Central hypothyroidism.
AB  - Central hypothyroidism is defined as hypothyroidism due to insufficient
      stimulation by thyroid stimulating hormone (TSH) of an otherwise normal thyroid
      gland. It has an estimated prevalence of approximately 1 in 80,000 to 1 in
      120,000. It can be secondary hypothyroidism (pituitary) or tertiary
      hypothyroidism (hypothalamus) in origin. In children, it is usually caused by
      craniopharyngiomas or previous cranial irradiation for brain tumors or
      hematological malignancies. In adults, it is usually due to pituitary
      macroadenomas, pituitary surgeries or post-irradiation. Fatigue and peripheral
      edema are the most specific clinical features. Diagnosis is established by the
      presence of normal to low-normal TSH on the background of low-normal thyroid
      hormones, confirmed by the thyrotropin releasing hormone stimulation test.
      Therapy includes use of levothyroxine titrated to improvement in symptomology and
      keeping free T4 in the upper limit of normal reference range.

PMID- 21966669
TI  - Bifunctionalized SBA-15 as a novel micropipette tip sorbent for selective removal
      and enrichment of biomolecules.
AB  - Selective enrichment or removal of specific proteins prior to analysis can
      minimize nonspecific interferences as well as information loss, which has been an
      important issue in current proteomics fields. In this work, two kinds of
      mesoporous silica SBA-15 (mean pore diameter of 5 nm and 7 nm), bifunctionalized
      with quaternary ammonium and C18 groups via silylanization reaction, was used to
      investigate the adsorption behavior for different proteins (bovine serum albumin
      (BSA), ovalbumin (OVA), hemoglobin (Hb), lysozyme (Lys) and cytochrome c (cyt
      c)). As possessing anion exchange (quaternary ammonium) groups, the
      bifunctionalized SBA-15 showed selective adsorption of the negative charged
      proteins, BSA and OVA. Based on these properties, sequential fractionation based
      on different SBA-15 materials as micropipette tip sorbents was developed for
      sample preparation prior to protein analysis. As expected, after the sequential
      treatment of the sample, the detection signal of the high abundant BSA was
      significantly decreased and that of the low abundant cyt c was obviously
      enlarged, which solved the problem that low abundant protein was suppressed by
      adjacent high abundant protein. The sample preparation technique significantly
      improved protein identification and this sequential fractionation approach could
      be potentially applied to extend information on the protein identification for
      biological samples with a wide dynamic range.

PMID- 21966670
TI  - Design of a dual-signaling sensing system for fluorescent ratiometric detection
      of Al3+ ion based on the inner-filter effect.
AB  - A dual-signal sensing system based on the inner-filter effect (IFE) was
      demonstrated, in which the combination of two signaling mechanisms allows metal
      binding to turn on two fluorescence emission bands, independently. A proof-of
      concept fluorescent ratiometric assay for Al(3+) in pure aqueous solution is
      presented. The proposed assay is based on the Al(3+)-induced color and
      fluorescence changes of Alizarin red S (ARS) and IFE between ARS and meso-tetra(N
      methyl-4-pyridyl)porphine tetratosylate salt (TMPyP). In the absence of Al(3+),
      the absorption spectrum of the ARS in 0.2 M HAc-NaAc buffer (pH 5.5) has a strong
      peak at 420 nm, significantly overlapping with the excitation of TMPyP. ARS is
      expected to be capable of functioning as a powerful absorber to tune the emission
      of TMPyP on account of the spectral overlap. Binding of Al(3+) with ARS forms a
      fluorometric ARS/Al(3+) complex and shifts the maximum absorbance from 420 nm to
      480 nm, which overlaps negligibly with the excitation of TMPyP and turns on the
      proper emission spectrum for TMPyP. Under the optimum conditions, The
      fluorescence intensity ratio, F(585)/F(651), responds to Al(3+) over a dynamic
      range of 0.1-1.5 MUM, with a limit of detection of 40 nM, where F(585) and F(651)
      are the fluorescence intensity at 585 nm and 651 nm in the absence or presence of
      Al(3+), respectively. Further application in Al(3+)-spiked water samples
      suggested a recovery between 95 and 108%. The fluorescence response is highly
      selective for Al(3+) over other metal ions with the addition of thiourea as the
      masking agent.

PMID- 21966671
TI  - A sensitive choline biosensor using Fe3O4 magnetic nanoparticles as peroxidase
      mimics.
AB  - A sensitive choline biosensor using Fe(3)O(4) magnetic nanoparticles and a
      choline oxidase modified gold electrode was developed. Fe(3)O(4) magnetic
      nanoparticles as peroxidase mimics used in the choline biosensor can not only
      improve the sensitivity of the response signal, but also possess the favorable
      properties of stability, magnetic separation and easy preparation, etc. When
      using the reduction currents of square wave voltammetry as the detection signals,
      the interferences of ascorbic acid and uric acid to the choline biosensor can be
      reduced effectively. The reduction currents of the square wave voltammetry were
      increased with the logarithm values of the choline chloride concentration (from
      10(-9) to 10(-2) M), the detection limit was estimated to be 0.1 nM (S/N = 3).
      This choline biosensor also exhibited favorable selectivity and stability in the
      determination of choline chloride.

PMID- 21966672
TI  - Iron-substituted SBA-15 microparticles: a peroxidase-like catalyst for H2O2
      detection.
AB  - In this communication, we demonstrate our recent finding that iron-substituted
      SBA-15 (Fe-SBA-15) microparticles possess intrinsic peroxidase-like activity and
      can catalyze the oxidation of peroxidase substrate 3,3',5,5'-tetramethylbenzidine
      (TMB) by H(2)O(2) to develop a blue color in aqueous solution, leading to a
      simple approach towards colorimetric detection of H(2)O(2) with a linear
      detection range from 0.4 MUM to 15 MUM (r = 0.997) and a detection limit of 0.2
      MUM.

PMID- 21966673
TI  - Glycosylated nucleoside lipid promotes the liposome internalization in stem
      cells.
AB  - We report new glycosyl-nucleoside-lipid based liposomes decorated with sugar
      moieties. The GNL-liposomes feature a suitable glycosylated surface for their
      internalization into ADSC stem cells.

PMID- 21966674
TI  - Oxidative desulfurization of dibenzothiophene with hydrogen peroxide catalyzed by
      selenium(IV)-containing peroxotungstate.
AB  - With stoichiometric H(2)O(2) as oxidant, dibenzothiophene (DBT) is oxidized to
      its corresponding sulfone with high efficiency, catalyzed by a sub-valence
      heteronuclear peroxotungstate,
      [C(18)H(37)N(CH(3))(3)](4)[H(2)Se(IV)(3)W(6)O(34)], under mild biphase conditions
      and the catalyst shows remarkable selectivity of catalytic oxidation towards DBT,
      cinnamyl alcohol and quinoline.

PMID- 21966675
TI  - Learning tools: visual aids.

PMID- 21966676
TI  - Proceedings from BioMicroWorld 2009, the third International Conference on
      Environmental, Industrial and Applied Microbiology, held in Lisbon, Portugal,
      during 2-4 December 2009.

PMID- 21966677
TI  - Proceedings from the NVVI-Dutch society for Immunology Course, Lunteren, March
      31st-April 1st, 2010.

PMID- 21966678
TI  - Proceedings from the 28th International Symposium on Chromatography, Valencia,
      Spain.

PMID- 21966679
TI  - Proceedings of the International Symposium on "Levodopa: Back to the Future",
      April 3-4, 2009, Catania, Italy.

PMID- 21966680
TI  - Suction extraction: taking a grip on  intracapsular cataract extraction with  the
      erysiphake.

PMID- 21966681
TI  - Authors' response.

PMID- 21966682
TI  - Authors' response.

PMID- 21966683
TI  - SAC C VS disease surveillance report: Cases of jejunal haemorrhage syndrome in
      Scottish dairy cows.

PMID- 21966685
TI  - Research as a syllabus in medical undergraduate curriculum: is this important in
      nurturing future researchers?

PMID- 21966684
TI  - Boundaries around the drug industry: a prescription.

PMID- 21966686
TI  - Examiners' perception of  Objective Structured  Examination in colposcopy.

PMID- 21966687
TI  - Perceptions of educational  climate in a Canadian  medical radiation science 
      programme.

PMID- 21966688
TI  - An evaluation of a final year  work-shadowing attachment.

PMID- 21966689
TI  - Statistics: a learning needs assessment.

PMID- 21966690
TI  - 8 ways to smooth your CIS install. Health management technology asked select
      industry experts to respond to the following question: what are the best ways to
      minimize the pains associated with selecting and adopting a clinical information
      system?

PMID- 21966691
TI  - The future of mobile healthcare: World Congress conference spotlights mobile
      health strategies.

PMID- 21966692
TI  - New York lawmaker in touch with health care debate. As a doctor, Hayworth is in
      tune with health care issues.

PMID- 21966693
TI  - Maintaining standards through tougher times.
AB  - Speaking at the Health Estates and Facilities Management Association's (HEFMA)
      2011 national conference in Torquay, Mike Hall, general manager, facilities, at
      Salford Royal NHS Foundation Trust, explained how, with estates and facilities
      departments expected to significantly contribute to the 20 billion pounds
      sterling in savings the NHS must achieve over the next 3-4 years, the Trust is
      striving to maintain exemplary patient care, efficiency, and productivity
      standards, while simultaneously ensuring that all staff understand what is
      expected of them, and challenging conventional employment terms and conditions
      "to root out underperformers". As HEJ editor Jonathan Baillie reports, his
      presentation was followed by a broader look at the challenges facing a large NHS
      acute Trust as the service gears up for the proposed new commissioning structure.

PMID- 21966694
TI  - 'Cradle to cradle' approach explained.
AB  - At a recent seminar in London, "Sustainability and the environment in the real
      world", speakers from multinational flooring specialist, Tarkett, and major users
      of the company's floorcoverings, examined how specifier, customer, consumer, and
      regulatory demands for more "sustainable" flooring systems are impacting on this
      important product sector, and how such pressures have increasingly seen
      introduced a new generation of flooring systems that not only incorporate a high
      recycled content, offer a full "cradle to cradle" lifecycle, and have low
      emissions, but are also produced with careful "stewardship" of, for instance, the
      water and energy consumed in their manufacture.

PMID- 21966695
TI  - Survey serves up food for thought.
AB  - An independent survey into hospital food standards in England conducted earlier
      this year for the Soil Association saw over half of those patients surveyed admit
      they would not be happy serving the meals they received during a recent hospital
      stay to a child, while 29% said the food was so bad that, at times, they could
      not recognise what was on their plate. Nearly of quarter of the 1,000 indviduals
      questioned by OnePoll, meanwhile, had opted out of hospital catering altogether-
      choosing to have every meal brought in to them by visiting relatives; nor, the
      Soil Association says, is enough English hospital food being locally or
      sustainably sourced.

PMID- 21966696
TI  - Prehospital management of the anemia patient: what you need to know about this
      common blood disorder and its clinical manifestations.

PMID- 21966697
TI  - Agency and capabilities to achieve a work-life balance: a comparison of Sweden
      and Hungary.
AB  - This study develops a conceptual framework with a capabilities and agency
      approach for analyzing work-life balance (WLB) applied in two societies (Hungary
      and Sweden), which have different working time regimes, levels of precarious
      employment, and gender equality discourses and norms. Inspired by Amartya Sen, we
      present a model illustrating how agency freedom for WLB depends on multiple
      resources at the individual, work organizational, institutional, and
      normative/societal levels. Using a unique qualitative survey conducted in two
      cities, Budapest and Stockholm, we analyze how mothers and fathers subjectively
      experience the tensions between family and work demands, and their possibilities
      for alternative choices (agency freedom). We find similarities in these tensions
      involving time pressure and time poverty, cutting across gender and education.
      Our Hungarian parents, nevertheless, experience greater agency inequalities for
      WLB, which reflect weaker institutional resources (conversion factors) as well as
      cultural/societal norms that act as constraints for WLB claims in the workplace
      and household. Our study reveals that Swedish parents, both men and women,
      express a strong sense of entitlement to exercise rights to care.

PMID- 21966698
TI  - Social policies related to parenthood and capabilities of Slovenian parents.
AB  - We apply Sen's capability approach to evaluate the capabilities of Slovenian
      parents to reconcile paid work and family in the context of the transition to a
      market economy. We examine how different levels of capabilities together affect
      the work-life balance (WLB) of employed parents. We combine both quantitative and
      qualitative methodological approaches. The results of our quantitative and
      qualitative research show that increased precariousness of employment and
      intensification of work create gaps between the legal and normative possibilities
      for successful reconciliation strategies and actual use of such arrangements in
      Slovenia. The existing social policies and the acceptance of gender equality in
      the sphere of paid work enhance capabilities for reconciliation of paid work and
      parenthood, whereas the intensification of working lives, the dominance of paid
      work over other parts of life, and the acceptance of gender inequalities in
      parental and household responsibilities limit parents' capabilities to achieve
      WLB.

PMID- 21966699
TI  - Tensions between work and home: job quality and working conditions in the
      institutional contexts of Germany and Spain.
AB  - Good jobs can generate capabilities that allow employees to avoid tensions
      between work and family/home. Following the conceptual framework of Amartya Sen,
      we examine how job-related demands and resources are related to the level of
      interference, as well as satisfaction with managing work and home in Spanish and
      German employees, using three different large-scale European surveys: European
      Quality of Life Survey and two waves of the European Social Survey. We find that
      long working hours systematically increase tensions between work and home, as do
      time pressure, job-related stress, and working hard. Job control or autonomy at
      work, which is hypothesized to expand individuals' capabilities and agency, tends
      to increase work-home interference rather than alleviate it. Family
      responsibilities and household demands do not seem relevant to the tensions
      employees experience at the work-home interface. This also holds true for women,
      which is a surprising result in view of the "double burden" hypothesis. Employed
      mothers in Germany and Spain are a select group of women, as combining employment
      with raising children in conservative-corporatist and conservative-familialist
      states may be particularly problematic. Thus while the institutional contexts of
      Germany and Spain curtail women's ability to reconcile employment and parenthood,
      the mothers (and fathers) who are employed do not experience significantly higher
      levels of work-family/home tensions than nonparents.

PMID- 21966700
TI  - Work, family, and managerial attitudes and practices in the European workplace:
      comparing Dutch, British, and Slovenian financial sector managers.
AB  - Managers are key actors shaping employees' capabilities to utilize work-life
      policies. However, most research on managers' implementation of these policies
      has been conducted in liberal welfare states and ignores the impact of
      institutional context. In this study, we situate managers within specific
      workplace and national layers of context. We investigated how managers in
      financial organizations in the Netherlands, UK, and Slovenia talk about the
      utilization of work-life policies. Managers' discourses stressed disruption and
      dependency considerations in these case studies, as in the US research. However,
      a further management discourse of the moral case or right thing to do also
      emerged. The lack of resources for replacing staff on leave creates disruption
      and reduces managers capability to support the use of work-life policies, even
      when they are statutory or if managers are inclined be supportive (dependency or
      moral argument). This is likely to impact on parents' capabilities.

PMID- 21966701
TI  - Food inflation in South Africa: some implications for economic policy.
AB  - This paper analyses the trends in food price movements in South Africa between
      1980 and 2008. There are three main results emanating from the analysis in this
      paper. Firstly, food price movements have played a large role in generating
      inflationary episodes in South Africa. Secondly, while external influences do
      matter, South African food price movements are mainly due to domestic influences.
      This implies that national policy has an important role to play in taming
      domestic food price inflation. Thirdly, given the strong second round impacts,
      food price movements warrant special attention in monetary policymaking. Core
      measures of inflation that exclude food price movements may not accurately
      reflect the underlying inflationary pressures in the economy and could compromise
      the attainment of the goal of price stability.

PMID- 21966702
TI  - Feet and fabrication: footbinding and early twentieth-century rural women's labor
      in Shaanxi.
AB  - The early twentieth-century transformations of rural Chinese women's work have
      received relatively little direct attention. By contrast, the former custom of
      footbinding continues to fascinate and is often used to illustrate or contest
      theories about Chinese women's status. Arguing that for rural women at least,
      footbinding needs to be understood in relation to rural economic conditions, the
      authors focus on changes in textile production and in footbinding in two counties
      in Shaanxi province. Drawing on historical sources and their own interview data
      from rural women who grew up in this period, the authors find evidence that
      transformations in textile production undercut the custom of footbinding and
      contributed to its rapid demise.

PMID- 21966703
TI  - Queering Taiwan: in search of nationalism's other.
AB  - This article deals with the formation of Taiwan's homosexual cultural politics in
      the 1990s, the impact and implications of which are yet to be examined within the
      larger context of Taiwan's cultural and political development and ethnic
      relationships. It is argued that the rise of this cultural politics is both a
      reflection and a source of a growing sense of identity crisis on the island. By
      examining the configurations of "queer" in various discursive domains, this
      interdisciplinary study seeks to delineate the cross-referencing ideological
      network of this cultural movement and its entanglement with the complexity of
      Taiwan's nationalism. At the same time, to the extent that this movement tends to
      present itself as a radical politics from a privileged epistemological and
      cultural standpoint, this claimed radicalism is also scrutinized for its
      problematics and ironies.

PMID- 21966704
TI  - Playing With "patriotic fire": women and football in the Antipodes during the
      Great War.
AB  - The revelation that women first played Australian Rules football during the
      period of the Great War is an important element in overall understandings of how
      both masculine and feminine ideals were challenged and redefined by sporting
      practices in a time of general social flux. This paper reveals that the genesis
      of the women's code was in Western Australia, where contests occurred as early as
      1915. Three years later, with the war nearing its conclusion, the template of
      women's involvement in charity matches with strong military and patriotic
      overtones was adopted in the state of Victoria, the code's heartland.
      Investigations such as this one, indicative of the complex relationships between
      sport and gender during the First World War, offer scope for deeper comprehension
      of a much-studied military conflict, and point the way forward for those that
      bemoan the static agenda of research into women's football.

PMID- 21966705
TI  - Standardizing the home?: Women reformers and domestic service in New Deal New
      York.
AB  - In response to the poor working conditions suffered by domestics struggling to
      survive the Depression, middle-class women's organizations initiated various
      legislative reforms aimed at tackling the problems they believed plagued the
      occupation. Throughout these years, organized women debated three key pieces of
      reform related to domestic service: efforts to suppress street-corner markets,
      health requirements for prospective domestics, and state-level wage and hour
      reform. These reforms were united by the rhetoric of privacy, which clubwomen
      used both to oppose wage and hour reform and to support requirements that
      domestics have physicals before applying for work. This article examines the fine
      distinction that middle-class women's organizations drew between public and
      private in the appropriate application of government power and the resulting
      conflict between progressive women's gender ideology and their most deeply-held
      reform ideals. In doing so, it reveals organized women's struggle to reconcile
      their humane ideals with the reality in their kitchens.

PMID- 21966707
TI  - Separate and unsanitary: African American women railroad car cleaners and the
      Women's Service Section, 1918-1920.
AB  - The Women's Service Section (WSS) investigated federally controlled railroad
      stations and yards at the end of World War I. Few women worked in car cleaning
      before the war, and railroad management preferred to block women workers,
      especially African Americans, from gaining any kind of foothold in railroad work.
      African American women were the single largest group of railroad car cleaners
      during this period but they were routinely denied adequate facilities, including
      toilets, locker rooms, and dining facilities throughout the railroad system. By
      raising the issues of facilities, workers' rights, and public health, these women
      shaped federal policy and widened the agenda of the WSS to include a direct
      attack on segregated workplaces. This article argues that African American women
      car cleaners launched an industrial campaign that wove together concerns about
      racism, sexism, and health issues, and successfully removed barriers to women
      working in a predominately male industry.

PMID- 21966706
TI  - Disunity in diversity: the controversy over the admission of black women to the
      General Federation of Women's Clubs, 1900-1902.
AB  - From 1900 to 1902, the General Federation of Women's Clubs' official commitment
      to "unity in diversity" was tested to the limits when an explosive debate over
      the admission of African American women's clubs deeply, and in some cases
      irreparably, divided individual clubs and state federations and nearly resulted
      in the loss of half of the organization's burgeoning membership. The controversy
      reveals a captivating, complicated, and at times bizarre struggle between
      Northern and Southern white members of the General Federation to defend their
      particular views of race and, in many cases, to obfuscate their own deep-seated
      racial prejudices. Most members ultimately sacrificed principle for the sake of
      federation unity, albeit a unity without racial diversity, and thus squandered
      the opportunity to combine the talents and energies of all organized women in an
      effort toward social justice and humanitarian reform.

PMID- 21966708
TI  - Gender, professionalization, and the child in the Progressive Era: Patty Smith
      Hill, 1868-1946.
AB  - This article discusses the career of Patty Smith Hill, a major figure in the
      American kindergarten movement, in the context of the Progressive Era in American
      history. Hill, an educator and child-welfare activist, became known both as a
      reformer of early-childhood education and as an advocate of the inclusion of the
      kindergarten, originally a private institution, in public-school systems. The
      article acknowledges this as one of the most significant achievements of the
      woman-led reform movements of the Progressive Era, but at the same time notes
      that it involved a substantial transfer of power from the women who had
      originally developed the kindergarten to the male principals and superintendants
      who now supervised kindergarten teachers, often without much understanding of
      their distinctive methods and aims. As a professor at Columbia Teachers College,
      Hill also exercised an international influence. Hill's career exemplifies broader
      patterns of women's professionalization during the late-nineteenth and early
      twentieth centuries.

PMID- 21966709
TI  - "Give the ladies a chance": gender and partisanship in the Prohibition Party,
      1869-1912.
AB  - In the nineteenth-century Prohibition Party, American women ascribed new gendered
      meanings to party work traditionally performed by male partisans, and also drew
      upon their gendered roles as women, mothers, and wives to create new partisan
      strategies. This article investigates the political culture that sustained a
      remarkable departure from traditional Democratic and Republican practices, and
      further explores why women's contributions to the Prohibition Party declined in
      the early-twentieth century. In so doing, it traces how gender and gender roles
      shaped the meaning of party and politics, and elucidates the interplay between
      institutions, constituencies, and policy during one of America's most tumultuous
      political eras.

PMID- 21966710
TI  - Rights to food with a human face in the global south.
AB  - This article seeks to dispel the popular myth surrounding the food crises which
      precipitated food riots in the global South in 2008. Arguing from a structural
      and historical perspective, the article suggests that global hunger is a deep
      rooted crisis that is embedded in the social and structural variables associated
      within the nation-state that places a restraint on the self-regulating capacity
      of nation-states in the South. Internationalizing the food crisis, however, will
      do more harm to the south's agricultural transformation and rural development.
      The article argues for integrated rural development that will increase output
      growth through an institutional, technological, and marketing strategy.

PMID- 21966711
TI  - South Africa's abortion values clarification workshops - an opportunity to deepen
      democratic communication missed.
AB  - A rich literature exists on local democracy and participation in South Africa.
      While the importance of participation is routinely built into the rhetoric of
      government, debate has increasingly focused on the dysfunctionality of
      participatory mechanisms and institutions in post-apartheid South Africa.
      Processes aimed ostensibly at empowering citizens, act in practice as instruments
      of social control, disempowerment and cooptation. The present article contributes
      to these debates by way of a critique of the approach used by the South African
      state, in partnership with the non-governmental sector, in what are called
      abortion "values clarification" (VC) workshops. This article examines the
      workshop materials, methodology and pedagogical tools employed in South African
      abortion VC workshops which emanate from the organization Ipas - a global body
      working to enhance women's sexual and reproductive rights and to reduce abortion
      related deaths and injuries. VC workshops represent an instance of a more general
      trend in which participation is seen as a tool for generating legitimacy and "buy
      in" for central state directives rather than as a means for genuinely deepening
      democratic communication. The manipulation of participation by elites may serve
      as a means to achieve socially desirable goals in the short term but the long
      term outlook for a vibrant democracy invigorated by a knowledgeable, active and
      engaged citizenry that is accustomed to being required to exercise careful
      reflection and to its views being respected, is undermined. Alternative models of
      democratic communication, because they are based on the important democratic
      principles of inclusivity and equality, have the potential both to be more
      legitimate and more effective in overcoming difficult social challenges in ways
      that promote justice.

PMID- 21966712
TI  - Changelings: transformative perceptions of San Jose's street children, 1965-1981.
AB  - Between 1965 and 1981, Costa Ricans changed their perceptions of which
      characteristics they thought defined appropriate urban childhoods. By 1981, the
      model of a modern, urban Costa Rican child was that of a child who attended
      school, did not work on the streets, and played in specifically designated
      places. Children who did not fit this mold began, in the late 1970s and early
      1980s, to be viewed as dangerous to society and as evidencing social pathology.
      Whereas children who worked on the streets during the 1960s were considered part
      of the urban landscape, and their childhoods, though difficult, were not
      perceived as deviant, these same children, two decades later, were viewed as
      marginal and problematic. To trace this change, this article focuses on the
      changing perceptions about children on the streets that writers for and public
      contributors to La Nacion, one of the preeminent Costa Rican newspapers, show
      during the sixteen-year period under analysis.

PMID- 21966713
TI  - The Pied Piper of the ghetto: Lyndon Johnson, environmental justice, and the
      politics of rat control.
AB  - When Congress rejected President Lyndon Johnson's Rat Extermination and Control
      Bill in the summer of 1967, in a mood of growing conservatism, it inadvertently
      sparked a heated political controversy that brought the desperate conditions of
      life in inner-city America into sharp focus. This article focuses on the issue of
      rat infestation to explore the conditions of "urban blight" that
      disproportionately afflicted ghetto communities in the United States during the
      1960s and that represented a form of environmental inequality linked to racial
      marginalization and poverty. It is suggested that a growing awareness of
      environmental aspects of inequality increasingly fueled ghetto discontent,
      feeding the outbreak of riots during the "long, hot summers," and spurring
      liberals to think of new ways to understand the problems of inner-city poverty.

PMID- 21966714
TI  - Research, statistics, and causality in dentistry.

PMID- 21966715
TI  - From knowledge to practice wisdom.

PMID- 21966716
TI  - Integrating nursing science in the education process.
AB  - With the present shortage of nursing faculty and the imminent retirement of
      current faculty, clinical nurses are encouraged to step into academia, bringing
      their enthusiasm, knowledge, and clinical experience. As nurses enter the world
      of nursing education, they will face two challenges: the paradigm shift from
      clinical nursing to learning process, and the vast diversity of students. Turning
      to the foundations of nursing, a young nurse educator generated teaching-learning
      strategies through integration of nursing sciences as a guide to becoming an
      effective educator.

PMID- 21966718
TI  - Snippets.

PMID- 21966717
TI  - Robert Willan: a Quaker physician who founded the morphologic approach to modern
      dermatology.

PMID- 21966719
TI  - Courtesan, concubine, whore: Apollodorus' deliberate use of terms for
      prostitutes.

PMID- 21966720
TI  - Evaluation of a pilot communication skills training intervention for minority
      cancer patients.
AB  - The aim of this study was to pilot test in a minority cancer patient population a
      communication workshop to improve doctor-patient communication skills. Thirty-two
      patients participated. Eighteen evaluated a face-to-face workshop, while 14
      completed surveys only. Participants in the workshop group completed the Patient
      Report of Communication Behavior (PRCB) before and after the workshop and a
      course evaluation. Participants did not differ on baseline PRCB scores. Posttest
      scores were significantly higher than pretest scores (p < 0.01). All participants
      agreed or strongly agreed that they would use the communication skills; 93%
      agreed or strongly agreed that the skills would improve their health care.

PMID- 21966721
TI  - The way we used to eat: diet, community, and history at Rome.

PMID- 21966722
TI  - Psychometric properties of the Death Anxiety Scale (DAS) among terminally ill
      cancer patients.
AB  - Research conducted with the terminally ill population in relation to death
      anxiety is rare and mostly outdated. The purpose of this study was to evaluate
      the psychometric properties of the widely used Death Anxiety Scale (DAS) on a
      sample of terminal cancer patients.Additionally, validation studies of the DAS
      have exclusively used traditional statistical methods for analysis. The current
      study utilized an item response theory technique (IRT), namely the Rasch Rating
      Scale model for data analysis. The methodology employed may be useful for other
      researchers conducting validation studies from an IRT perspective.

PMID- 21966723
TI  - Land and sea: Italy and the Mediterranean in the Roman discourse of dining.

PMID- 21966724
TI  - Religiosity and physical and emotional functioning among African American and
      White colorectal and lung cancer patients.
AB  - The literature suggests that religiosity helps cope with illness. The present
      study examined the role of religiosity in functioning among African Americans and
      Whites with a cancer diagnosis. Patients were recruited from an existing study
      and mailed a religiosity survey. Participants (N = 269; 36% African American, 56%
      women) completed the mail survey, and interview data from the larger cohort was
      utilized in the analysis. Multivariate analyses indicated that in the overall
      sample religious behaviors were marginally and positively associated with mental
      health and negatively with depressive symptoms. Among women, religious behaviors
      were positively associated with mental health and negatively with depressive
      symptoms. Religiosity was not a predictor of study outcomes for men. Among
      African Americans, religious behaviors were positively associated with mental
      health and vitality. Among Whites, religious behaviors were negatively associated
      with depressive symptoms. These findings suggest a mixed role of religious
      involvement in cancer outcomes. The current findings may have applied potential
      in the areas of emotional functioning and depression.

PMID- 21966725
TI  - Psychosocial care for adolescent and young adult hematopoietic cell transplant
      patients.
AB  - Psychological issues following hematopoietic cell transplantation (HCT) are
      unfortunately common. Literature specific to the transplant experience for the
      needs of adolescents and young adults (AYA) is lacking. The purpose of this
      article is to (1) describe the allogeneic transplant experience for AYA
      transplant patients during the first year following transplantation including
      demographic and treatment characteristics, (2) present AYA data obtained during
      and following a six-part posttransplant discharge study, (3) illustrate typical
      AYA experiences using case studies, and (4) propose AYA intervention strategies
      within Erickson's stages of psychosocial development. A quality of life model
      provided the research conceptual framework, and the content analysis framework
      for the qualitative research. Themes that emerged within each domain were the
      following: sexuality/fertility, fatigue, depression/poor coping/habits,adherence
      issues, use of technology, dependency issues, changes in roles/relationships,
      issues with school/education, financial issues, family problems/issues,
      miscellaneous, religion/spirituality, fear of future, uncertainty, life, death,
      more life appreciation. These data guide us for providing targeted interventions
      for the needs of this AYA population. This paper has presented literature and
      developmental theory, qualitative and qualitative data from an intervention
      study, and clinical cases in order to propose a developmental treatment model for
      AYA transplant patients. A coordinated and multidisciplinary approach is needed
      for the HCT patient who is an AYA.

PMID- 21966726
TI  - Predicting mental quality of life in breast cancer survivors using comparison
      participants.
AB  - The objective of this research is to propose a comprehensive model for the
      prediction of long-term mental health in breast cancer survivors diagnosed 5 to
      15 years earlier, compared to female participants referring to the most stressful
      event that occurred within the last 20 years. Nearly 300 survivors and 132
      comparison participants were consulted using a questionnaire, which evaluated
      personality variables, transactional variables, and current mental quality of
      life. Structural equation modeling was used. The transactional proposed model was
      able to account for long-term mental health variance in both groups but was more
      relevant to women with breast cancer.

PMID- 21966727
TI  - "Waiting for the other shoe to drop:" distress and coping during and after
      treatment for breast cancer.
AB  - This study explored distress and coping strategies during and after breast cancer
      treatment. Open ended interview questions were used to explore stress and coping
      across the illness trajectory and during continuing care. With permission, 49 of
      the 50 interviews were audiotaped. Interviews also involved the use of the Impact
      of Events Scale-Revised (IES-R), the Ways of Coping (WAYS) and the Lubben Social
      Support Network Scale (LSNS-6). Data analysis involved a sequential quantitative
      (dominant)-qualitative (non-dominant) design.A mean-split procedure was used to
      compare lower and higher distress. The overall IES-R score as well as the
      Avoidance, Intrusions, and Hyperarousal subscales were all statistically
      significant between the higher-lower distress groups. Fourteen of the 22
      individual IES-R items were significantly different between groups.WAYS subscale
      scores were not significantly different but 21% of the individual items were.
      Stress involves (1) physical stressors and(2) psychosocial stressors: (fear of
      recurrence and family-focused concerns). Coping involves (1) activity-based
      strategies, (2) cognitive strategies, and (3) spiritual strategies. Breast cancer
      survivors experience persistent concern about recurrence and uncertainty about
      the future. Understanding the nature of distress and how women cope during and
      after treatment are key to improved care for women who have breast cancer.

PMID- 21966728
TI  - Horizontal women: posture and sex in the Roman convivium.

PMID- 21966729
TI  - Comments on antimicrobial  resistance surveillance.

PMID- 21966730
TI  - Morality versus science  in the animal welfare debate.

PMID- 21966731
TI  - Diversity in veterinary  schools and beyond.

PMID- 21966732
TI  - Diversity in veterinary  schools and beyond.

PMID- 21966733
TI  - Proposed changes  to veterinary curriculum.

PMID- 21966734
TI  - Debate on nonveterinarians  performing veterinary  procedures.

PMID- 21966735
TI  - Veterinarian-client-patient  relationships at low-cost  clinics.

PMID- 21966736
TI  - Panel offers recommendations to aid animals in Japan's 'no-go' zone. Protocols,
      procedures for pets, livestock, wildlife contaminated by radiation.

PMID- 21966737
TI  - 3 universities interested in veterinary programs. One proposed college developing
      an accelerated curriculum.

PMID- 21966738
TI  - Class size increases  spur mixed reactions. Some say more graduates needed to
      fill  shortage areas.

PMID- 21966739
TI  - AVMA VP Strother on the future of veterinary medicine. Sees need for greater AVMA
      engagement with third- and fourth-year students. Interview by R. Scott Nolen.

PMID- 21966740
TI  - Feline-friendly handling  guidelines aim for perfect  veterinary visits.
      Veterinary team, pet owner  have a hand in limiting stress in cat patients.

PMID- 21966741
TI  - Lawsuits result from dispute  over noncompetition contract.

PMID- 21966742
TI  - Sports medicine  and rehab specialty to publish  certification requirements.
      Achievement marks culmination of years-long process.

PMID- 21966743
TI  - Modest veterinarian, beloved author. Dr. James A. Wight's experiences in barns
      and homes reached millions.

PMID- 21966744
TI  - Animal rescue coalition  concludes Haiti relief work.

PMID- 21966745
TI  - Public health vets want more to join their ranks.

PMID- 21966747
TI  - [Is surveillance of exhaustive work a possible alternative?].

PMID- 21966746
TI  - Health related quality of life and psychosocial correlates among HIV-infected
      adolescent and young adult women in the US.
AB  - In this study HIV health-related quality of life (HIV-HRQOL) is examined among
      179 behaviorally infected adolescent and young adult women. Modifiable
      psychosocial variables including depression, stigma, social support, and illness
      acceptance, and the biological end-points of CD4 cell count and viral load were
      explored in relation to HIV-HRQOL. The three factors of the HIV-HRQOL measure
      include current life satisfaction, illness related anxiety and illness burden.
      Bivariate linear regression analysis demonstrated statistically significant
      associations for all psychosocial variables and HIV HRQOL factors (p < .01), but
      not for biological end-points. In multivariate linear regression analysis
      significant associations remained between: depression (p = .006), illness
      acceptance (p < .001), social support (p = .001), and current life satisfaction,
      and depression (p = .012), illness acceptance (p = .015), and illness burden. A
      trend in association was noted for HIV stigma, with current life satisfaction and
      illness related anxiety but did not reach statistical significance (p = .097 and
      p = .109 respectively). Interventions that effectively decrease stigma and
      depression and increase social support and illness acceptance will likely improve
      the well-being and quality of life of HIV-infected adolescent women.

PMID- 21966748
TI  - Toward a typology of Roman public feasting.

PMID- 21966749
TI  - Marriage, identity, and the tale of Mestra in the Hesiodic Catalogue of women.

PMID- 21966750
TI  - [Roles of costimulatory molecules in bronchial asthma].

PMID- 21966751
TI  - Cigarette smoking and Parkinson's disease: a meta-analysis.
AB  - Many but not all studies have indicated that smoking is inversely associated with
      Parkinson's disease (PD). Meta-analysis of epidemiological studies on smoking and
      PD was performed to summarize data from published studies. Fifty-four
      epidemiological studies (48 case-control and 6 cohort studies, 53 publications)
      were identified for potential inclusion in meta-analysis. The summary risk
      estimates for current smokers, former smokers, and ever (current and former)
      smokers were 0.31 (95% confidence interval (CI) = 0.25-0.38), 0.72 (95% CI = 0.63
      0.83) and 0.55 (95% CI = 0.51-0.59), respectively. In stratified analysis by
      study design, smoking had a somewhat greater impact on PD risk in cohort studies
      than in case-control studies. However, meta-regression indicated that the study
      design did not significantly contribute to heterogeneity. Additional analyses
      were restricted to case-control studies because of the sufficient number of
      studies. Stratified analysis by ethnicity indicated that the summary OR for ever
      smokers was nonsignificantly smaller in Asian populations than in Caucasian
      populations. In stratified analysis by source of controls, former smoking was
      significantly associated with a decreased risk of PD in hospital-based case
      control studies but was marginally associated with a decreased risk in population
      based case-control studies. The source of controls did not contribute
      significantly to heterogeneity. PD risk associated with ever-smoking was
      significantly lower for a hospital-based approach than a population-based
      approach. Among current smokers, the association held true to the same extent for
      both approaches. This meta-analysis indicated that smokers have a lower risk of
      PD. As PD is a multifactorial disease, further investigation of the smoking-gene
      interaction on PD risk may lead to a better understanding of the pathogenesis of
      PD.

PMID- 21966752
TI  - [Types of anxiety of couples treated with assisted fertilization regarding
      hypothetical donation of embryos at Clinical Hospital of Chile University].
AB  - BACKGROUND: There are no empirical studies which have explored the
      experimentation with human embryos in Latin America. In general, there are no
      frameworks that regulate neither lawful matters of assisted reproduction nor the
      possibility of experimentation with human embryos, and the ethical frames are
      limited to those adopted by each center. Currently, to think about the real
      possibilities of experimentation with embryos goes beyond a legal frame, since
      the opinion of the potential actors is not known either (gamete or embryo
      donors). The experimentation with embryos is practically a reality in developed
      nations and Latin America continues appearing almost only as a potential market
      for the scientific advance. OBJECTIVE: To determine the anxiety types of the
      couples treated with assisted fertilization before hypothetical donation of
      embryos for investigation, by a mixed quantitative and qualitative methodology.
      PATIENTS AND METHODS: An oral semistructured interview was made individually to
      ten participants (seven women and three men) who had gone like patients of the
      Assisted Fertilization Program of the Gynecology and Obstetrics Service of the
      Clinical Hospital of the University of Chile. The scale of anxiety of the
      analysis of the verbal conduct method of Gottschalk and collaborators was applied
      to them. RESULTS: The most frequently associated types of anxiety to the
      hypothetical situation of donation of embryos for scientific research were the
      fault, separation, and mutilation anxiety. CONCLUSIONS: It is recommended to
      develop educative programs regarding the culture of embryo donation for treatment
      of couples with fertility problems, as well as for investigation, and to develop
      educative programs about the meaning of relationship and of embryo status.

PMID- 21966753
TI  - [Results' analysis of estradiol and progesterone supplementation in luteal phase
      vs progesterone alone in an assisted reproduction program].
AB  - OBJECTIVE: To correlate estradiol and progesterone concentrations in luteal phase
      with pregnancy rates, and to determine the real value of estradiol administration
      during luteal phase support. PATIENTS AND METHODS: In a prospective and
      comparative study, 69 patients who underwent IVF-ET program were divided in two
      groups: group 1 (n = 32) received luteal phase support only with progesterone and
      group 2, (n = 37) luteal phase support with estradiol and progesterone. Ovarian
      stimulation was made with recombinant FSH and GnRH analogues (agonists or
      antagonists) and 24 hours after oocyte retrieval we began luteal phase support:
      group 1 progesterone (in oily solution) 100 mg/day IM, and group 2 same
      progesterone doses plus 2 mg of estradiol valerianate. Statistical analysis was
      performed using students' t- test and ROC curves. RESULTS: No statistical
      differences were observed in age, preovulatory estradiol levels, oocytes
      retrieved, fertilization rates, number of embryos transferred, or difficulty of
      embryo transfer among groups. The overall pregnancy rate was of 34.78% per cycle,
      no significant differences were observed among groups (37.5 vs 32.43%). We
      observed greater incidence of miscarriage in group 2 (4.35 vs 0%), without
      statistical significance. When comparing estradiol levels and pregnancy outcomes,
      higher levels were observed in the pregnancy group (403.3 vs 221.85 pg/mL) on day
      7 post-transfer. Same results were reported for progesterone levels (107.04 vs
      240.76). We determined that estradiol levels on day 7, higher than 244 pg/mL,
      could predict pregnancy with sensitivity of 58% and specificity of 70%, whereas
      progesterone levels greater than 108.6 ng/mL had specificity and sensitivity of
      50 and 70%, respectively. CONCLUSIONS: We couldn't determine any advantage with
      estradiol supplementation during luteal phase support; however, measurement on
      day 7 of estradiol and progesterone allowed a greater predictive accuracy of
      pregnancy outcome.

PMID- 21966754
TI  - [Fetal lung maturity delayed on diabetic pregnancies].
AB  - OBJECTIVE: To determine the fetal lung maturity in a group of pregnant patients
      complicated by gestational diabetes or impaired glucose tolerance, metabolic
      controlled patients, as well as to identify the modifications of the
      phospholipids lung profile by effect of antenatal steroids. PATIENTS AND METHODS:
      231 pregnant patients were included in an observational, longitudinal, clinical
      and descriptive study from January 1st 2000 to April 30th 2003. All those
      included presented gestational diabetes or impaired glucose tolerance according
      to the criteria of Carpenter. The metabolic control was demonstrated by means of
      glycosylated hemoglobin figures minor to 6.5%, and glucose monitoring (<95 mg/dL
      before meals and < 120 mg/dL two hours after each meal). The amniocentesis was
      performed just before the use of antenatal steroids and 48 hours after. The
      phospholipids lung profile was performed applying the Hallman and Kulovich
      method. RESULTS: By means of the Student's t-test non significant results were
      obtained for the general characteristics of both groups, except for the evolution
      of the phospholipids lung profile in the post-treatment group with antenatal
      steroids. As for the evolution of the fractions in the profile of the weekly
      phospholipids, an ANOVA test was applied with a p < 0.001 coefficient of
      statistical significance for the phosphatidylglycerol fraction. CONCLUSIONS:
      Delay of fetal lung maturity was shown in all the fractions of the phospholipids
      lung profile. In the group of patients with pregnancies of 36 weeks or more there
      was shown no correspondence among gestational age and the state of fetal lung
      maturity (60.75%), in comparison to that reported in existing literature. There
      were not reported cases of respiratory distress syndrome in the newborns.

PMID- 21966755
TI  - [Ocular changes after hormone replacement therapy in postmenopausal women. A
      preliminary report].
AB  - BACKGROUND: Ocular function is modified with hormone therapy; however, reports in
      literature are highly controversial. OBJECTIVE: To analyze how hormone therapy
      modifies intraocular pressure and the number of tears shed by Mexican women.
      PATIENTS AND METHODS: Eighteen postmenopausal women were studied and randomly
      divided into two groups, according to the treatment they received: group 1,
      conjugated equine estrogens (CEE) 0.625 mg/day (n=9) (hysterectomized women with
      bilateral oophorectomy) and group 2, CEE 0.625 mg/day plus chlormadinone 1 mg/day
      (n=9) (women with intact uterus). Changes in intraocular pressure and Schirmer's
      test were analyzed at baseline and three months after the treatment. Statistical
      analysis was performed with Student's t test for independent and paired samples.
      RESULTS: There were no significant differences in intraocular pressure or
      Schirmer's test among groups, neither when comparing baseline and final results
      in each group independently. CONCLUSION: We could not demonstrate the effect of
      hormone replacement therapy on intraocular pressure and on Schirmer's test after
      three months of its administration.

PMID- 21966756
TI  - [Connective tissue degradation in human amniochorion after stimulation with
      choriodecidual lymphocytes infected with group B streptococci].
AB  - OBJECTIVE: To identify whether soluble products from choriodecidual blood cells
      stimulated with group B streptococci (GBS) induce connective tissue degradation
      in human amniochorion. MATERIAL AND METHODS: Blood samples from choriodecidual
      compartment were collected by direct aspiration from placental cotyledons
      draining blood and represent local circulating cells. Samples were divided into
      two aliquots: one was stimulated with GBS (1 X 10(6) CFU/mL) and the other was
      kept free of bacteria as negative control. After overnight incubation, plasmas
      were separated. Chorioamnion explants were stimulated with 10% plasma for 12h at
      37 degrees C in 5% CO2. MMP-9 proteolytic activity was measured in the
      supernatants by gelatin-zymography and IL-1beta and TNF-alpha were quantified by
      ELISA. Distribution of the collagenous fibrils in explants was examined by
      electron microscopy. STATISTICAL ANALYSIS: three independent experiments on
      duplicate were carried out and the statistical significance of experimental
      differences between groups was assessed with ANOVA test. RESULTS: MMP-9, IL-1beta
      and TNF-alpha production was significantly higher in supernatants from explants
      co-cultured with choriodecidual plasma from blood previously infected with GBS,
      compared with control plasma. Accompanying extensive changes of connective tissue
      arrangement confirm induction of extracellular matrix degradation. CONCLUSIONS:
      Choriodecidual plasma from blood stimulated with GBS is enriched with biochemical
      signals that enhance the MMP-9, IL-1alpha and TNF-beta production by
      amniochorion. These findings suggest that local circulating cells are capable to
      act in response to GBS choriodecidual infection through extracellular matrix
      degradation and the consequent rupture of membranes.

PMID- 21966757
TI  - [Latin-American position about current state of hormone therapy. Position
      Statement of the Group of Latin American Experts on Hormonal Therapeutic
      Materials].

PMID- 21966758
TI  - [Fetal ovarian cyst. A report of a case].
AB  - Fetal ovarian cyst is uncommon; it represents the second place of fetal abdominal
      tumors, after urinary tract tumors. The cause of fetal ovarian cysts still
      remains unclear, although it is likely to be promoted by hormones. Its prognosis
      is usually good. Differential diagnosis should rule out urinary tract
      malformations. A case of a female newborn with giant fetal ovarian cyst,
      diagnosed on week 37 of the pregnancy period, treated with exploratory laparotomy
      and cyst exeresis, with serum cystadenoma histopathology diagnosis is presented.

PMID- 21966759
TI  - [Douglascopy as a diagnostic resource to use in gynecological urgencies.1950].

PMID- 21966760
TI  - [Prognostic value on recovery rates for the application of sperm preparation
      techniques and their evaluation in sperm function].
AB  - OBJECTIVE: To evaluate sperm recovery and total sperm motility in three different
      sperm preparation techniques (density gradient, simple washing and swim-up).
      PATIENTS AND METHODS: A total of 290 subjects were randomly evaluated from
      November 2001 to March 2003. The density gradient method required Isolate (upper
      and lower layers). Centrifugation was performed at 400 g for 10 minutes and
      evaluation was done using the Makler counting chamber. The simple washing method
      included the use of HTF-M complemented with 7.5% of SSS, with centrifugation at
      250 g, obtaining at the end 0.5 mL of the sperm sample. The swim-up method
      required HTF-M complemented with 7.5% of SSS, with an incubation period of 60
      minutes at 37 degrees C. RESULTS: The demographic characteristics evaluated
      through their standard error, 95% ICC, and 50th percentile were similar. The
      application of multiple comparison tests and analysis of variance showed
      significant differences between the sperm preparations before and after
      capacitation. It was observed a superior recovery rate with the density gradient
      and swim-up methods; nevertheless, the samples used for the simple washing method
      showed a diminished sperm recovery from the original sample. CONCLUSIONS: Sperm
      preparation techniques have become very useful in male infertility treatments
      allowing higher sperm recovery and motility rates. The seminal parameters
      evaluated from the original sperm sample will determine the best sperm
      preparation technique in those patients who require it.

PMID- 21966761
TI  - [Breast density and its association to polimorphism of the estrogen-receptor
      alpha gene Pvull and Xbal].
AB  - OBJECTIVE: To study the influence of ER-alpha on mammographic density. MATERIAL
      AND METHODS: We selected 87 healthy women (age 49.8 +/- S.D. 6.12 years). We
      obtained the body mass index (BMI), and a fasting blood sample for hormone
      determinations and DNA extraction. ER-alpha genotyping was carried out by PCR and
      digestion with a Pvull and Xbal restriction endonucleases. Mammographic density
      was assigned by the radiologist used three categories of fatty, average and
      dense. RESULTS: Mammographic density was significantly associated with estradiol
      (p = 0.04), estrone (p = 0.04), and FSH (p = 0.02). The BMI was not associated
      with Pvull and Xbal genotypes and marginally with mammographic breast density (p
      = 0.06). CONCLUSIONS: We did not observe compelling evidence of an association
      between variant alleles of genotypes estrogen receptors alpha and breast density.

PMID- 21966762
TI  - [Doppler ultrasound to detect Rh: a systematic review].
AB  - BACKGROUND: Red cell alloimmunization is an important cause of perinatal
      morbidlity and mortality. Invasive procedures used to diagnose fetal anemia are
      associated with serious fetal and maternal complications. The development of
      noninvasive techniques as Doppler ultrasound can help us in the fetal anemia
      diagnosis. OBJECTIVES: To evaluate the effect of the Doppler ultrasound in
      prediction of fetal anemia caused by red cell alloimmunization. Strategy search:
      Relevant studies were identified by reviewing the registry of COCHRANE, and OVID,
      PROQUEST, MEDLINE and EMBASE data bases from 1966 to 2004. SELECTION CRITERIA:
      All prospective studies with clinically relevant results with comparison of
      Doppler ultrasound in fetal umbilical artery, fetal descendent aorta, middle
      cerebral fetal artery or esplecnic fetal artery with hemoglobin or fetal
      hematocrit. DATA COLLECTION AND ANALYSIS: Data were extracted from each report.
      The quality revision of the studies and the data compilation were made by the
      reviewers. MAIN RESULTS: Eighteen articles were included. Two studies reached the
      level of evidence 1 for diagnostic tests. The diagnostic tests had variations
      depending on the different cut-off of each study. Studies with level 1 of
      evidence reported detection of 100% for moderate to severe fetal anemia.
      CONCLUSIONS: Implementation of Doppler ultrasound for prediction of fetal anemia
      in complicated pregnancies with alloimmunization could reduce the number of
      invasive procedures and therefore its complications. The level of present
      evidence reveals to us that the studies do not fulfill the criteria of
      methodological quality.

PMID- 21966764
TI  - [Domestic violence: an approach from gynecology and obstetrics].
AB  - Violence against women represents a serious violation of women's human rights and
      has been recognized as a clinical and public health problem, independently of
      nationality, ethnicity, cultural norms and socioeconomic status. One of the most
      common forms of violence against women is that perpetrated by an intimate male
      partner. The intimate partner violence has short-term and long-term negative
      health consequences, which provoke a poor quality of life with high use of health
      services, and even the suicide and homicide of women. Specifically, abuse during
      pregnancy is associated with sexually transmitted diseases, anemia, first and
      second trimester bleeding, less than optimal weight gain, deleterious perinatal
      outcomes (low birth weight, miscarriage, and fetal distress) and maternal or
      infant deaths. The purpose of this review is to emphasize the serious health
      consequences of the partner violence, and to compile the studies that have
      measured violence during pregnancy, particularly in Latin America.

PMID- 21966763
TI  - [Therapy with dehidroepiandrosterone improves symptoms in perimenopausal women].
AB  - BACKGROUND: Depressive symptoms that occur with the onset of menopause are
      accompanied by changes in circulating neurotransmitters levels; these biochemical
      variations are considered to cause psychoemotional symptoms. OBJECTIVE: To assess
      the effect of DHEAsupplementation and its efficacy for relieving symptoms of
      emotional and psychological distress, as well as the action on circulating
      neurotransmitters in perimenopausal women. PATIENTS AND METHODS: An open,
      comparative, clinical study included twenty perimenopausal women who received
      oral DHEA doses and ten women acted as comparison group. SETTING: the Endocrine
      Research Unit, Instituto Mexicano del Seguro Social, Mexico City. Interventions
      and main outcome measures consisted of oral DHEA doses of 50 mg/day for six
      months. Green scale for climacteric women and Quality of Life Menopause Scale
      (QUALMS) were used to measure emotional and psychological symptoms and well
      being. Serum levels of DHEA-S, dopamine, serotonin, and beta-endorphin were
      quantified by specific assays at baseline and at the end of the treatment.
      RESULTS: Alleviation of psychoemotional symptoms was observed in all but 4
      treated women. Baseline levels of serum DHEA-S, serotonin and beta-endorphin
      increased significantly (p < 0.001) from 2.1 +/- 0.5 to 8.3 +/- 2.1 micromol/L,
      215.3 +/- 86.4 to 310.4 + 150.1 ng/mL, and from 9.8 +/- 2.1 to 16.2 +/- 7.1
      pmol/L respectively (means +/- SE) after treatment. In contrast, dopamine levels
      were unchanged. CONCLUSIONS: DHEA relieved emotional and psychological symptoms,
      and elevated both serotonin and beta-endorphin levels in perimenopausal women.

PMID- 21966765
TI  - [Virilizing adrenal adenoma: a report of a case].
AB  - Androgen excess can be due to different entities such as polycystic ovarian
      syndrome, ovarian tumors or adrenal tumors. It is presented the case of a 26 year
      old woman that suffered from amenorrhea, hirsutism, voice deepening, reduction of
      mammary volume and 10 kg weight loss, without response to different treatments.
      At physical exam she had hirsutism (24 points, Ferriman-Gallaway) the clitoris
      had 3 cm length. Laboratory: androstenedione 29.5 ng/mL, DHEAS >1000 microg/dL, T
      6.23 ng/mL, 17 OHP 4.9 ng/mL. At pelvic ultrasound the uterus and left ovary were
      normal, the right ovary had subcortical follicles no greater than 3 mm. The CAT
      scan and nuclear magnetic imaging of adrenal glands showed an oval
      retroperitoneal image of 7.2 x 6.5 x 8.4 cm at the right adrenal gland. Surgery
      was performed and the right adrenal gland excised. The histopathologic report
      indicated a benign cortical adenoma. The patient's postsurgical evolution was
      satisfactory with regression of the virilizing signs, with spontaneous return of
      menstrual periods. Hirsutism can be the initial sign, and even in some occasions
      the only one of different pathologies. The study of the hyperandrogenic patient
      should be integral with clinical, hormonal and imaging evaluations to be able to
      specify the origin of androgen production.

PMID- 21966766
TI  - [Medical education for 21st century: an approach to the problem].

PMID- 21966767
TI  - [Pelvic absimetry. 1950].

PMID- 21966768
TI  - [The epidemic has reached us].

PMID- 21966769
TI  - [Comparison of laparoscopic vs. laparotomy treatment in ovarian teratomas].
AB  - BACKGROUND: Benign cystic teratoma is one of the most common benign tumors of the
      ovary, according to international series represents between 44 and 62% of all
      ovarian tumors diagnosed in women younger than 40 years. OBJECTIVES: To evaluate
      and compare the efficacy and safety between laparoscopy and laparotomy in the
      management of ovarian teratomas, as well as the recurrence between both
      techniques. MATERIALS AND METHOD: Retrospective, clinical series study involving
      169 cases of ovarian teratomas operated at the Instituto Nacional de
      Perinatologia Isidro Espinosa de los Reyes in the period comprehended between
      2000-2008. The cases were divided into the ones solved by laparoscopy,
      corresponding to group 1 (102 cases) and 67 cases solved by laparotomy,
      corresponding to group 2. RESULTS: Group 1 (laparoscopic approach) consisted of
      102 patients (60.3%), and group 2 (laparotomy approach) had 67 patients (39.7%).
      Surgical bleeding: 55.7 +/- 21.4 mL vs. 91.6 +/- 29.2 mL (p < 0.0001), hospital
      stay: 1.6 +/- 0.57 vs. 2.7 +/- 0.42 days (p < 0.0001), surgical time: 110.3 +/-
      27.2 vs. 83.6 +/- 26.9 minutes (p < 0.0001), teratoma size: 7.2 +/- 2.3 vs. 11.5
      +/- 4.2 cm (p < 0.0001) in groups 1 and 2, respectively. Teratoma rupture had
      57.8% incidence (59 cases) in group 1, and 16.4% in group 2 (11 cases).
      Laparoscopy was a risk factor for broken open for ovarian cyst (OR: 6.9; CI 95%:
      3.3-14.8). Not a single case was complicated by chemical peritonitis in any study
      group. CONCLUSIONS: Laparoscopic approach to teratomas is a safe and efficient
      procedure, it does not increase complications in comparison to the laparotomy
      approach; it presents less bleeding and short hospital stay, offering a quick
      recovery.

PMID- 21966770
TI  - [Birth defects associated with increased nuchal translucency].
AB  - BACKGROUND: Nuchal translucency is widely used to screen for trisomy 21 in the
      first trimester of pregnancy. It has also been associated with other chromosomal
      abnormalities, genetic syndromes and congenital defects. OBJECTIVE: To evaluate
      the perinatal outcome of patients who showed nuchal translucency greater or equal
      to 95th percentile during the first trimester ultrasound screening, which
      underwent fetal karyotype. MATERIAL AND METHOD: Case series. Fetuses with nuchal
      translucency greater or equal to 95th percentile were evaluated by fetal
      karyotype, second-trimester structural ultrasound scan, fetal echocardiography
      and postnatal clinical genetic evaluation, attended in the servicio de Genetica
      of the Instituto Nacional de Perinatologia Isidro Espinosa de los Reyes. RESULTS:
      48 fetuses were evaluated. The karyotype was normal in 39 (81%) and abnormal in 9
      (19%) cases of which three had trisomy 21, three monosomy X, two trisomy 18 and
      one 47,XYY In the cases with normal karyotype, 13 (33%) showed an abnormal second
      trimester ultrasound scan; among them, 12 had major congenital defects, 5 of them
      had abnormal cardiac findings that were confirmed by fetal echocardiography. In
      the group of 26 fetuses with normal karyotype and ultrasound, only 2 patients had
      minor birth defects. CONCLUSIONS: Increased fetal nuchal translucency is
      frequently associated with chromosomal abnormalities and several congenital
      defects, mostly heart defects and genetic syndromes. Our findings are in
      accordance with other published reports where a complete follow-up of all
      patients with increased nuchal translucency is recommended even if they have a
      normal karyotype, due to the increased risk of having other congenital defects or
      syndromic entities.

PMID- 21966771
TI  - [Lactic acid and lactoserum in vulvovaginal infections].
AB  - BACKGROUND: The discomfort of vaginal infection symptoms is a frequent cause of
      medical consultation. OBJECTIVE: To determine the degree of satisfaction reported
      by a group of Mexican patients used the combination lactoserum lactic acid and to
      the relief of vulvovaginal symptoms (odor, itching and burning) or not associated
      with infection and the safety of that combination when used for external genital
      hygiene daily. PATIENTS AND METHOD: Clinical observational, prospective,
      multicenter open and made with a group of Mexican women 18-60 years of age,
      residents in cities across the country with some or vulvovaginal symptoms: foul
      odor, itching, burning. All participants were told the application, once daily,
      2.5 to 5 mL of shampoo, for 14-21 days. The patients rated the presence and
      severity of vulvar discomfort with visual analogue scale. The data were analyzed
      with Statistical Analysis System statistical package version 9.1, the
      quantitative variables by calculating the mean +/- standard deviation,
      categorical variables by calculating percentages. RESULTS: We included 559
      patients who answered the questionnaires before and after treatment. The time-use
      shampoo study was variable, with less than seven days were 25 patients (4.5%), 8
      to 14 days 123 patients (22.0%) of 15 to 21 days, 208 patients (37.3%) and 178
      patients (31.9%) used it more than 21 days. The average time elapsed since the
      start of treatment until the disappearance of vulvar discomfort was 4.3 days,
      with a SD of 3.1. In symptomatic patients the average was 4.2 days (SD 3.3),
      while in asymptomatic patients was 4.4 days (SD 3.0), virtually the same between
      groups. At the time of the final visit, 92.2% of patients reported "feeling of
      cleanliness" in the genital area, 91.7% "fresh feeling" and 93.9% "general
      feeling of wellbeing". 97.2% felt that the product is "user friendly", 94.9%
      considered it "soft and gentle to the skin" and 95.2% described it with "pleasing
      aroma". CONCLUSIONS: Shampoo daily female external genital hygiene, the reason
      for this study is useful in the disappearance of the symptoms associated with
      infection or vulvovaginal.

PMID- 21966772
TI  - [Phenomenological study of infertile women with obesity].
AB  - BACKGROUND: Obesity is a condition strongly associated with polycystic ovary and
      other conditions that interfere with or complicate the treatment of assisted
      reproduction. OBJECTIVE: To examine, from a phenomenological point of view, the
      perception of infertile women obesity problem before undergoing assisted
      reproduction treatment. This analysis should help to design a psychotherapeutic
      strategy focused on this problem. PATIENTS AND METHOD: One hundred patients with
      infertility, with a BMI equal to or greater than 30, candidates for assisted
      reproductive treatments in the service of Human Reproduction, Centro Medico
      Nacional 20 de Noviembre, ISSSTE. The phenomenological qualitative analysis was
      performed in 72 women who agreed to be interviewed in depth. The phenomenon is to
      study obesity in infertile women candidates for assisted reproduction treatment.
      RESULTS: Obese infertile women subject to assisted reproduction treatment
      perceive their difficulty losing weight is closely associated with infertility.
      Most patients had social feelings of worthlessness, sadness, worthlessness, and
      family rejection. The inability to obtain a steady weight loss is regarded as a
      minor frustration that sterility. CONCLUSION: It is very important to perform
      intensive, multidisciplinary labor, which is focused on concepts associated with
      psychological distress, such as: management of depression by sterility, control
      of anxiety and stress, control of social pressures and management of the illusion
      of motherhood. Also rely on specialists of eating habits and exercise.

PMID- 21966773
TI  - [Influence of the high peak serum estradiol on the outcome of in vitro
      fertilization cycles].
AB  - BACKGROUND: For the use of assisted reproductive technologies of high complexity
      (IVF-ET and ICSI) is essential to proper ovarian stimulation with recombinant FSH
      drugs menotropins, as well as the use of GnRH analogues. OBJECTIVE: To correlate
      serum estradiol level on day 10th with the outcome of in vitro fertilization
      cycles. MATERIAL AND METHOD: Retrospective study of 523 IVF cycles, selected and
      analyzed from 2005 to 2009. Patients underwent individualized stimulation
      protocols with gonadotropins and agonist (late luteal phase). The patients were
      divided into three groups according with the serum level of estradiol on day 10th
      of stimulation: Group I, patients with serum level of Estradiol below 1,000
      pg/mL; Group II, with levels between 1,000-4,000 pg/mL; and Group III, with
      levels above 4,000 pg/mL. Peak serum estradiol levels, oocyte number,
      fertilization rates, implantation rates, and pregnancy rates were compared among
      groups. RESULTS: The fertilization rate was 62.8 in Group I; 60.6% in Group II,
      and 54.2% in Group III. The pregnancy rate in Group I was 29.8%; in Group II,
      37.3%; and 24% for Group III. The implantation rates were 14, 22 and 14% for each
      group respectively (I, II and III). CONCLUSIONS: There is an inverse relationship
      between high peak serum estradiol levels and pregnancy rate; the implantation
      rate seems affected by the extreme levels of serum estradiol. The percent of
      total mature oocytes and fertilization rate improve with serum levels of
      estradiol at physiologic values.

PMID- 21966774
TI  - [Hippocrates is sick of misunderstanding and fatigue in society. How do I cure
      it?].
AB  - Is taken as a paradigm of the physician Hippocrates devoted to care of the sick
      individual. Under the format of a fictional history focus aspects of the
      existential problems that affect the current physician in the exercise of their
      profession to analyze its causes and suggests some possible interventions of the
      doctors themselves to solve them. It insists that medicine is the art of applying
      science and technology to solving health problems of the individual and society,
      in which doctors study and practice the profession to serve others and that
      medicine not a commodity to be bought or sold according to market rules. Also
      emphasizes the concept that health is a basic right of man and not a gift or
      compliment to anyone or only product of legislation. The medical fee is fair, but
      not enough on a salary or wage, let alone the terms of a tab based on the benefit
      to investors, institutions or intermediaries, must be complemented with
      additional features that guarantee a dignified life. These principles must be
      preserved at all costs and prevent the market outside interests or
      "industrialize." The first step to solving problems is to become aware of them
      and understand them. We present possible solutions.

PMID- 21966775
TI  - [Ovarian ginandroblastoma as a transcesarean incidental finding. A case report
      and literature review].
AB  - The gynandroblastoma is an extremely rare sexual cord stromal tumor, which
      contains both male and female elements, characterized by Sertoli or Leydig cells
      and granulose cells. We describe an ovarian gynandroblastoma in a 28 year-old
      female patient, found accidentally during a cesarean section operation. There is
      only one reported case in world literature occurring in a pregnant woman. The
      principal component we found was adult granulose cells, with a microfollicular
      pattern, and the presence of luteinized cells in some areas; besides we found the
      presence of well differentiated Sertoli cells elements, in addition to Leydig
      cells groups, in over 10% of the tumoral surface. Inmunohistochemical stainings
      were performed: citokeratin, which resulted positive in Sertoli cells and
      negative in granulose cells; and inhibin, which was positive in both components
      showing its mixed origin.

PMID- 21966776
TI  - [New guidance on labor analgesia. 1955].

PMID- 21966777
TI  - [Node status in 454 ductal breast cancers cases according to the association with
      in situ component].
AB  - BACKGROUND: Studies have shown that breast infiltrating ductal carcinoma develops
      from precursor lesions or pre-invasive. It is accepted that the risk of invasive
      ductal carcinoma increased slightly in hyperplasia, but especially in cases of
      atypical hyperplasia and intraductal carcinoma. OBJECTIVES: To evaluate and
      compare the nodal status between ductal breast cancer with in situ component
      (group 1) or without it (group 2). MATERIAL AND METHOD: Descriptive and
      retrospective study that included 454 ductal breast cancers. Data concerning
      clinical and pathological variables was collected. All data was compared between
      both groups. RESULTS: Among all cases, 176 (38.8%) showed positive lymph nodes,
      136 patients (39.5%) from group 1 and 40 cases (36.4%) from group 2. Among group
      1 cases, high-grade subgroup showed higher positive lymph node rate (82 cases,
      55.4%) than the extensive in situ carcinomas subgroup (84 cases, 49.7%). Both of
      them had a significant higher rate than group 2 cases (p = 0.003 y p = 0.028,
      respectively). Moreover, the low-grade in situ carcinomas without cellular
      necrosi had positive lymph nodes just in 30 cases (24%), significantly lower (p =
      0.034) than group 2. CONCLUSIONS: We did not find overall statistical differences
      between groups depending on in situ associated component. But when we analyzed in
      situ subgroups, we found differences with higher positive lymph node rate in high
      grade carcinomas and extensive in situ carcinomas subgroups, while lower
      affectation rates were observed in low grade carcinomas (without cellular
      necrosis), compared to the group of breast cancers without in situ component
      associated.

PMID- 21966778
TI  - [Hormone therapy effect in postmenopausal women with history of endometrial
      cancer].
AB  - BACKGROUND: The increase of endometrial cancer survivors' incidence let the
      question if the management of postmenopausal hormone therapy will increase the
      risk of carcinogenesis. OBJECTIVE: To determine the recurrence rate, in
      postmenopausal patients managed with hormonal therapy (HT) compared with patients
      without HT treated in El Instituto Nacional de Perinatologia Isidro Espinosa de
      los Reyes. PATIENTS AND METHOD: Retrospective, analytical, historical cohort. We
      analyzed 29 patients who met the inclusion criteria from January 1, 2000 to
      December 31, 2008 RESULTS: The average age for diagnosis of endometrial cancer
      was 45 years. 100% of the patients had surgical treatment (82.8% routine
      endometrial open approach, laparoscopic 17.2%). The 93% of patients had criteria
      to begin HT, however, was administered alone to 37% due to medical criteria, 36%
      received tibolona, 64% received estrogen with an average administration time of
      39 and 54 months for each one without affecting disease-free period. Patients who
      received hormonal therapy had no recurrence of disease-free period of 58 months.
      There was only one patient with recurrence for which no hormonal therapy was
      administered. CONCLUSIONS: Patients who were under hormonal therapy did not
      modify the rate of endometrial cancer recurrence compared with those without HT.
      Although we cannot conclude irrefutably the safety of hormone therapy, based on
      biological knowledge and the results of this study, hormone therapy can be safely
      administered in stage I and II.

PMID- 21966779
TI  - [Correlation of metabolic syndrome components in older Mexican women].
AB  - BACKGROUND: In woman aged over 60 years, body changes occur and might cause
      insulin resistance and metabolic syndrome. OBJECTIVE: To determine the
      relationship between the components of metabolic syndrome, insulin resistance and
      body mass index in women over 60 years, attended at the Geriatric Services in the
      Dr. Ignacio Morones Prieto Hospital in San Luis Potosi, Mexico. MATERIAL AND
      METHOD: We performed an observational, descriptive and transversal study with non
      probability sampling, selecting 61 women aged 60 years attended from 2006 to
      2008, who have measured the body mass index (BMI), insulin resistance and
      homeostasis model (HOMA2), and identifying the components of metabolic syndrome
      according to the criteria of the World Health Organization. We used descriptive
      and inferential statistics with r Pearson and Chi Square. RESULTS: The mean age
      was 68 years. The average HOMA2 were 1.4 and 75 percentile 1.9. The prevalence of
      metabolic syndrome was present in 23%. The association test with a p < 0.05 was
      considered significant for metabolic syndrome dysglucemia and obesity, but not
      for other components of metabolic syndrome. The triglycerides level correlated
      with insulin resistance (r = 0.325, p = 0.011), insulin resistance with glucose
      (r = 0.535, p = 0.000) and insulin resistance with BMI (r = 0.282, p = 0.28).
      CONCLUSIONS: It is important to properly define the components for the presence
      of metabolic syndrome in older women due to not all who qualify as obese have
      metabolic syndrome, and neither all the metabolic syndrome are associated with
      insulin resistance. The single alteration of one of the components of metabolic
      syndrome is not sufficient to cause insulin resistance.

PMID- 21966780
TI  - [Cervical length in predicting preterm labor].
AB  - BACKGROUND: Preterm birth is the birth occurring between 20-37 weeks gestation.
      Is responsible for 75% of neonatal mortality in infants without congenital
      malformations. OBJECTIVE: To determine the prognostic factor of cervical length
      measurement in threatened preterm labor, in patients treated at a hospital in
      Veracruz, Mexico. MATERIAL AND METHOD: Observational, prospective, longitudinal
      and descriptive study performed at the Obstetrics and Perinatology services of
      the Hospital General de Zona Num. 71, IMSS, from May to December 2007. INCLUSION
      CRITERIA: patients admitted to the obstetrics service with a diagnosis of preterm
      labor of 22 to 36 weeks, single gestation. EXCLUSION CRITERIA: history of
      premature rupture of membranes, uterine malformation, stillbirth, pregnancies of
      fetuses with birth defects, carriers of cerclage and a history of cervical cone
      biopsy. The cervicometry was performed with 7-9 MHz vaginal transducer; increased
      risk of preterm delivery were considered in patients with cervical length < 25
      mm, the existence of funnel was also assessed. We determined the sensitivity,
      specificity, positive predictive value and negative. RESULTS: We studied 73
      pregnant women diagnosed with preterm labor. The average age was 26.5 + 5.2
      years. Fourteen (19.2%) patients had a history of income for preterm labor in
      previous pregnancies. In ten patients (10.7%), measurement of cervical length <
      25 mm and the criterion of the number of weeks of preterm delivery (22-36) agreed
      (true positives); and 58 (79.5%) patients with cervical length > 25 mm and > or =
      38 weeks gestation also agreed (true negatives). CONCLUSIONS: The sensitivity to
      correctly predict preterm delivery was 71%, specificity of 98%, positive
      predictive value of 91% and negative predictive value of 94%, so the cervicometry
      is considered a useful tool for treatment and monitoring of preterm delivery.

PMID- 21966781
TI  - [Neurodevelopment at one year of age [corrected] in preterm newborns with history
      of maternal chorioamnionitis].
AB  - BACKGROUND: Recent clinical and epidemiological researches indicate that in
      preterm infants exposed to chorioamnionitis increases the risk of neurological
      disorders. OBJECTIVE: To know the neurological development in prematures newborn
      whose mothers suffered chorioamnionitis during pregnancy and to compare them with
      newborns without chorioamnionitis. MATERIAL AND METHOD: Is a prospective,
      comparative, cohort study, which included newborn infants with < 34 weeks of
      gestacional age and with weight < 1,500 g at birth, born in the Instituto
      Nacional de Perinatologia from August 1, 2005 to December 31, 2006. Two groups
      were divided (with and without antecedents of maternal chorioamnionitis), paired
      by weight and gestacional age, with complete neurological assessment at one year
      of age with the following instruments: Amiel Tison and Vojta assessment,
      audiological and prelanguage evaluations. RESULTS: 104 patients were included; 23
      belonged to the group with chorioamnionitis, and 81 to the group without
      chorioamnionitis. With the Amiel Tison assessment at one year of age we found a
      major alteration risk in active tone of the exposed children to chorioamnionitis
      (RR: 3.73, CI 95%: 1.05-13.3). The exploration of Vojta at the year of age was
      abnormal in the children exposed (RR: 1.64, CI 95%: 1.06-2.53). There were no
      differences in: hearing assessment, prelanguage skills, electroencephalography,
      visual and auditory evoked potentials of brain steam. CONCLUSIONS: In the exposed
      group to chorioamnionitis there were a major number of patients (56.5%) with
      neurological alterations versus the one without chorioamnionitis (29.6%, RR:
      1.90, CI 95%: 1.16-3.11). Motor alterations were found with more frequency in
      this study.

PMID- 21966783
TI  - [Malignant arrhenoblastoma. Case report and literature review].
AB  - The arrenoblastome is an ovary tumor with masculine hormone production,
      testosterone and other hormones. Other names are: stromatic tumor or gonadal
      stromatic tumor, also steroid cell tumor. They are rare tumors; represent 0.5% of
      all ovary tumors. It could be present in all age women groups, more frequently in
      young people. Most of times unilateral (95%), solids or quistic-solids.
      Anaplastic grade give them a malignity disease in 5 to 10 % cases. We report the
      case of a 35 year-old woman with clinical appearance of androgenism for ovary
      tumor, she was accepted for surgery, founded 7 liters of ascitis, produced for an
      ovary tumor, integral capsule, it produced masculine hormones. Histological study
      reported ovarian sex cord tumor, high grade, 30 cm size, integral capsule, all
      normally. Stage IC. Size and differential cellular grade need systemic
      chemotherapy. At the time of this report her tumoral marks are normal, and she
      has gradual diminution of virilizing characters produced for ovary tumor.
      Prognosis of the disease depends the grade of cell differentiation and stage in
      surgical-pathological events. Survival to five years stage I is approximate in 70
      to 90% of the cases. Angular stone treatment is surgery. Disseminate cases,
      chemotherapy or radiotherapy most be considerate. Usually arrenoblastome has poor
      possibilities of dissemination and considering the early detection the
      histological grade of healthy is very high.

PMID- 21966782
TI  - [Acute toxicity by methotrexate used for abortion purpose. Case report].
AB  - We report the case of a 16 years old female patient, with a pregnancy history of
      11.4 weeks by ultrasound and intrauterine fetal death. In a private clinic were
      prescribed methotrexate 500 mg intramuscular single dose, and vaginal
      misoprostol. She had a clinical feature of five days of evolution characterized
      by fever of 39 degrees C, nausea, general attack and vomiting. The initial
      diagnosis was severe sepsis secondary to septic abortion, oral candidiasis and
      acute poisoning by methotrexate. After that, she was referred to the Instituto
      Nacional de Perinatologia, where stayed with fever for four days, and was managed
      with hydration, antibiotics, folinic acid and alkalizing. Her recovery was
      gradual. She was discharged after 12 days with significant clinical improvement.
      The literature review describes that the use of methotrexate for abortion purpose
      with therapeutic-dose presents a similar adverse effects to those found in our
      patient, however there are no case reports that describe the use of this drug in
      macrodosis for the same purpose, and their cytotoxic effects. We present this
      case because the patient used a macrodosis of this antimetabolite and due to the
      premature and empirical management with folinic acid, joined with alkalinization
      of urine, is the ideal treatment and as it is illustrated in our case.

PMID- 21966784
TI  - [Current diagnosis and treatment of genital tuberculosis. 1955].

PMID- 21966785
TI  - [Prevalence of retrograde ejaculation in infertility associated to hypospermia].
AB  - BACKGROUND: Approximately 14% of couples of reproductive age have a fertility
      problem, defined as the inability to achieve pregnancy after a year of frequent
      intercourse without contraceptive protection. OBJECTIVE: To determine the
      prevalence of retrograde ejaculation in infertile patients with hypospermia and
      to establish the effects of the treatment. MATERIAL AND METHOD: Comparative
      study. A semen analysis of 207 patients with male infertility with hypospermia
      was performed. The patients with retrograde ejaculation were identified and its
      prevalence was calculated. Semen parameters were compared before and after
      treatment by means of a paired-t test. Hormonal levels also were compared between
      groups with and without retrograde ejaculation by means of a Mann-Whitney U test.
      RESULTS: Prevalence of retrograde ejaculation was 3.2% out of 2587 infertile
      patients. Within the group of 207 patients with hypospermia, 84 had retrograde
      ejaculation. After the treatment the seminal volume increased (from 1.2 to 1.5
      milliliters) and the number of mobile cells increased (from 47.2 to 62.5
      millions). The number of sperm in urine decreased (from 22 to 10 per high-power
      field). The patients with retrograde ejaculation had lower levels of follicle
      stimulating hormone, luteinizing hormone and testosterone than those without
      retrograde ejaculation. CONCLUSIONS: Retrograde ejaculation and hypospermia are
      both considered infrequent but important alterations in infertility. Prevalence
      of retrograde ejaculation in patients with hypospermia is 40.5%. Treatment
      increased seminal volume and the number of mobile cells in the ejaculated semen.
      It is necessary to perform future studies in order to determine the impact of
      severity of retrograde ejaculation on infertility.

PMID- 21966786
TI  - [Cesarean birth: justifying indication or justified concern?].
AB  - BACKGROUND: Caesarean section is the most common surgery performed in all
      hospitals of second level of care in the health sector and more frequently in
      private hospitals in Mexico. OBJECTIVE: To determine the behavior that caesarean
      section in different hospitals in the health sector in the city of Aguascalientes
      and analyze the indications during the same period. MATERIAL AND METHOD: A
      descriptive and cross in the top four secondary hospitals in the health sector of
      the state of Aguascalientes, which together account for 81% of obstetric care in
      the state, from 1 September to 31 October 2008. Were analyzed: indication of
      cesarean section and their classification, previous pregnancies, marital status,
      gestational age, weight and minute Apgar newborn and given birth control during
      the event. RESULTS: were recorded during the study period, 2.964 pregnancies
      after 29 weeks, of whom 1.195 were resolved by Caesarean section with an overall
      rate of 40.3%. We found 45 different indications, which undoubtedly reflect the
      great diversity of views on the institutional medical staff to schedule a
      cesarean section. CONCLUSIONS: Although each institution has different resources
      and a population with different characteristics, treatment protocols should be
      developed by staff of each hospital to have the test as a cornerstone of labor,
      also request a second opinion before a caesarean section, all try to reduce the
      frequency of cesarean section.

PMID- 21966787
TI  - [Evaluation of efficacy of ketoconazole 800 mg-clindamycin 100 mg tablets vaginal
      against ketoconazole 800 mg- clindamycin 100 mg vaginal capsules in candida
      vaginitis and vaginosis].
AB  - BACKGROUND: pharmaceutical forms (presentations) influence treatment compliance
      and therefore the effectiveness. Here we present the results in the relief of
      vaginitis and vaginosis with two different dosage forms. OBJECTIVE: To compare
      the efficacy and safety of a combination of ketoconazole 800 mg + clindamycin in
      soft vaginal gel capsules 100 mg (vaginal capsules) against ketoconazole 800 mg +
      100 mg clindamycin vaginal tablets (TV) in the management of vaginitis by C.
      albicans and/or vaginosis. MATERIAL AND METHOD: In a randomized, multicenter,
      comparative open label study, patients between 18 and 60 years with a diagnosis
      of vaginitis by C. albicans and/or vaginosis were included. Patients were
      evaluated clinically and direct exam of genital discharge and culture were
      performed. Patients were randomized to one of two treatments vaginal tablets or
      vaginal capsules, for 3 days. RESULTS: one hundred an sitxty nine patients were
      included, 85 in TV Group and 84 in vaginal capsules group. We found significant
      statistical difference in clinical response for tablet group at day three for
      burning p = 0.032 and itching p = 0.043. Microbiological cure was observed in
      patients with vaginitis by C. albicans, 92.5% in Group TV vs. 90.47% vaginal
      capsules group, all patients with G. vaginalis at baseline were negative for the
      organism at the end of the study, cure in patients with mixed infections were
      78.94% for TV group vs. 78.26% vaginal capsules; group no adverse events were
      reported during treatment. CONCLUSIONS: Treatment of vaginitis/vaginosis with
      vaginal tablets is clinically better than vaginal soft gelatin capsules both
      treatments were well tolerated.

PMID- 21966788
TI  - [Sexual and reproductive health among adolescents in high school in Guadalajara,
      Mexico].
AB  - BACKGROUND: Some authors define adolescence as the period of transition between
      childhood and adulthood, a stage characterized by the succession of major
      physiological, psychological and social human beings. OBJECTIVE: To determine the
      extent of information about preventing sexually transmitted diseases, knowledge
      and use of contraceptive methods, and to determine the percentage of high school
      teenagers who have initiated sex and age of onset. MATERIAL AND METHOD: We have
      realized a transverse descriptive study in 754 students from public junior high
      school number 54 in the city of Guadalajara, during the 2005-2006 school year. We
      have applied a survey that included questions about sexual health, and aspects as
      knowledge and use of contraceptive methods and concepts on the prevention of
      sexually transmitted diseases. Data were captured in a database in Excel, and
      then analyzed using SPSS. RESULTS: It included 641 students who agreed to
      complete the questionnaire by signed consent. The source of information on sex
      education is the most important school. The 84.5% of students surveyed know at
      least one contraceptive method, of which the condom is the best known (73.3%).
      The 84% of teenagers know how to prevent sexually transmitted diseases. Of all
      students, only 46 (7.2%) have initiated sexual activity of which 100% of males
      used contraception while only 63.3% of women did. CONCLUSIONS: It is necessary to
      establish or strengthen information programs on sexual health for adolescents,
      not only in schools if not in the media.

PMID- 21966789
TI  - [Caesarean section for ulcerative colitis].
AB  - We present a case of a 35-year-old patient with diagnosis of ulcerative colitis
      that presented failure and complications associated with medical treatment; with
      a report of a colonoscopy and biopsy of pancolitis with severe activity. The
      patient was submitted to laparoscopic restorative total proctocolectomy with
      ileal "J" pouch anal anastomosis. Two months later the ileostomy was reversed.
      The patient received progesterone at the same time she was receiving
      immunosuppressive drugs. This was suspended two months after the second colon
      surgery. The patient did not require treatment with ovulation induction to
      achieve pregnancy. At the fourth month of gestation, the patient developed a
      perianal abscess, which was successfully drained. After multidisciplinary
      assessment in week 38 of gestation, it was decided to perform cesarean birth as a
      way to not affect the ileal pouch and the anastomosis of the digestive tract. At
      present time, the patient has had no further complications.

PMID- 21966790
TI  - [Intravenous procaine as analgesic in obstetrics. 1955].

PMID- 21966791
TI  - [Modified Tei index, interobserver agreement related to sonographer experience
      level].
AB  - BACKGROUND: increasing numbers of studies that attempt to introduce the Tei index
      as part of fetal assessment in different conditions (corrected diaphragmatic
      hernia, supraventricular tachycardia, fetal inflammatory response, cystic
      adenomatoid disease, fetal-fetal transfusion, etc.). OBJECTIVE: To determine the
      interobserver agreement in measuring the modified Tei index in observers with
      different levels of experience in obstetric ultrasound. MATERIAL AND METHOD:
      Three observers were classified according to their level of experience (A, B and
      C) and selected 65 images to analyze the modified Tei index interobserver
      agreement. If all observers felt unanimously that were eligible for analysis, the
      image was selected. Each observer made the measurements independently. Once
      complete measurements, archived images and data were analyzed. RESULTS: The
      lowest variability of the modified Tei index was among the observers A/C
      (standard deviation of the differences of 27% versus 30% (B/C), versus. 40%
      (A/B). The correlation coefficient interclass of the three observers together was
      a regular on the scale of Landis and Koch, and substantial for observer A. The
      lowest variability of individual parameters was for ejection time. Interobserver
      variability was less gradually from first to fourth month observations.
      CONCLUSION: It has not been able to replicate the level of interobserver
      variability suggested in literature, by the effects of the learning curve in the
      procurement and selection of images. The modified Tei index interobserver
      variability was not found influenced by the level of operator experience in this
      context, but is considered not conclusive until obtain better evidence.

PMID- 21966792
TI  - [Short-term morbidity in newborns of the late preterm period].
AB  - BACKGROUND: Preterm birth is the most common cause of antepartum hospitalization.
      Currently little is known about neonatal morbidity in late preterm period.
      OBJECTIVE: To compare the short-term morbidity of infants born at term (37 0/7-41
      0/7 weeks gestational age) of low-risk pregnancies with newborns in the late
      preterm period (34 0/7 to 36 6/7 weeks gestational age) of low-risk pregnancies.
      MATERIAL AND METHOD: retrospective study of births in the Hospital Metropolitano,
      Secretaria de Salud del Estado de Nuevo Leon (Mexico) between January 1, 2005 to
      December 31, 2007. The study included preterm births in the late period of low
      risk pregnancies in spontaneous labor, and three control cases matched at term of
      the same features for each of the late preterm. Neonatal complications were
      compared among those born in the late preterm period to term infants. RESULTS:
      Late preterm births accounted for 2.2% of births and had higher incidences of
      respiratory distress syndrome, longer hospital stay, jaundice requiring
      phototherapy and hypoglycemia than those born at term. CONCLUSION: Late preterm
      births are a vulnerable group with significant neonatal morbidity. It is
      necessary to design strategies to improve neonatal outcomes in late preterm
      group.

PMID- 21966793
TI  - [Experience in the treatment of interstitial cystitis: review of 17 cases].
AB  - BACKGROUND: The Interstitial Cystitis (IC) has been considered in the past an
      uncommon pathology, however it has received a special attention during the last
      20 years, (1678 scientific articles published since 1984 to 2009). There are many
      therapeutic options not at all satisfactory because there isn't consensus about
      diagnostic and treatment. OBJECTIVE: To share our experiences in the treatment of
      interstitial cystitis, additionally, to comment on the therapeutic response of
      treatment used. MATERIAL AND METHOD: Observational, retrospective an analytic
      study of 17 treated patients from 22 with diagnosis of IC and Bladder Painful
      Syndrome (IC/BPS) were managed in Urodifem de Occidente, S.C. a private
      Urogynecologic unit between January 2001 and April 2010. The diagnosis was done
      in agreement with the concepts of Interstitial Cystitis group from clinical and
      cystoscopic characteristics. The treatment was: Dimethyl sulfoxide (DIMSO) and
      Pentosan Polysulfate. RESULTS: The evaluation was measured by Interstitial
      Cystitis Symptomatic Index (ICSI) and Interstitial Cystitis Problem Index (ICPI)
      both validated evaluation instruments, 82% of the patients had a significative
      improvement of symptomatology and quality of live The ICSI pre and post treatment
      was of 17.0 and 4.5 and the ICPI was of 14.8 and 4.1 respectively. CONCLUSION: We
      recommend the use of combine treatment of DIMSO and PPS in cases of I.C.

PMID- 21966794
TI  - [Comparative study of teenase and adults in rural communities of the state of
      Queretaro].
AB  - BACKGROUND: The teenage pregnancy is considered high risk. Often, teenagers have
      more episodes of eclampsia, preterm delivery, premature rupture of membranes, low
      birth weight, prematurity, postpartum complications, and surgical wound
      infections. OBJECTIVE: To evaluate nutritional condition of adolescent and adult
      mother's sons as well as its association with sociodemographic factors in rural
      communities in Queretaro, Mexico. MATERIAL AND METHOD: A comparative and
      transversal study with mothers under 20 years old and others from 20 to 35 years
      old whose children's range in age from 1 to 5 years old was made in Rural Health
      Centers. An aleatory sample with 275 children of each group was made. The
      association of nutritional condition with maternal age and sociodemographic
      variables was investigated. RESULTS: The height of adolescent mothers' sons was
      lower [(12.4%)T/E] than adult mothers' sons [(11.6%) P/T] with an excessive
      weight in 22.2 vs 19.6 % respectively. There was a statistical association
      between premature birth and adolescent mothers of law socioeconomic means. There
      was a connection between underweight children (chi2, p < 0.05) and mothers who
      had completed only elementary-level studies. However, no statistical relationship
      was found between the mother's age and child malnourishment, low birth weight, or
      the mother's level of schooling. CONCLUSIONS: Chronic malnourishment was similar
      to the national average. Excessive weight was encountered in both groups. There
      was a connection between adolescent mothers of low socioeconomic means and
      premature birth. Low levels of schooling on the pair of the mothers were
      associated with underweight children. But there was no relationship between the
      age of the mother and low birth weight, malnourishment, or the mother's level of
      schooling.

PMID- 21966795
TI  - [Uterine artery score in patients with systemic lupus erythematous as a predictor
      of intrauterine growth restriction].
AB  - BACKGROUND: Because of its high prevalence in the female population and its high
      incidence in reproductive age, Systemic Lupus Erythematosus can complicate
      pregnancy causing miscarriage, fetal death, preeclampsia, fetal growth
      restriction (up to 25%) and preterm birth. Doppler ultrasonography measures the
      flow in the uterine arteries, which is reduced in patients with preeclampsia and
      FGR, and thus is an ideal method for identifying pregnant women with a high risk
      of developing an adverse perinatal outcome. OBJECTIVE: Identify if Doppler
      ultrasound predicts FGR in patients with systemic lupus erythematosus. PATIENTS
      AND METHOD: In this observational, transversal, prospective study carried out
      from June 1st, 2010 to November 30th, 2010, in patients who had already been
      diagnosed with SLE, a complete clinical history was registered, blood samples
      taken and Doppler of uterine arteries between 18 and 23 gestation weeks taken
      (measuring the pulsatility index) RESULTS: Of the 17 women in the study, 6
      patients had a PI equal or greater than 1.45 (35.29%), of whom in 5 cases
      (29.41%), the product had FGR. Therefore the sensitivity of this test is 100%,
      with a specificity of 91%, a predictive positive value of 83% and a predictive
      negative value of 100%. With a p of 0.0010, which is considered extremely
      significant, and a confidence interval of 95%. CONCLUSIONS: There exists a high
      association between an abnormal PI and the development of FGR. Abnormal Doppler
      ultrasound of uterine arteries is useful for predicting FGR in pregnant women
      with SLE.

PMID- 21966796
TI  - [Takayasu's arteritis in pregnancy: report seven cases].
AB  - Takayasu's arteritis is a chronic and non-specific disease of young women in
      reproductive age that primarily affects the aorta, its branches and the pulmonary
      artery. Ramirez Cueto G. and Fernandez Del Castillo C. et al. published a case of
      pregnancy in Mexico and Takayasu's arteritis in 1968. There are no reports of
      this disease in pregnancy since. The purpose of this study is to describe the
      clinical course and perinatal outcome of seven pregnant patients with known
      diagnosis of Takayasu arteritis. The clinical course, laboratory findings,
      angiographic findings and perinatal outcomes were assessed in retrospect in seven
      pregnant patients with diagnosis of Takayasu's arteritis seen at the National
      Institute of Perinatology Isidro Espinosa Reyes (Mexico) during the period 2002
      2010. The results of the conducted follow-up of 7 patients pregnant with
      Takayasu's arteritis were: 3 patients were complicated with pre-eclampsia and 2
      newborn presented intrauterine growth restriction. Disease activity wasn't
      observed during pregnancy. No cases of congestive heart failure, brain ischemia
      or maternal deaths were presented. There were no fetal deaths. We didn't observed
      induced activity during pregnancy in the cases presented. The most common mother
      complication was type renovascular hypertension with added severe preeclampsia,
      which determined the presence of intrauterine growth restriction. There were no
      maternal or perinatal deaths.

PMID- 21966797
TI  - [Arterial thrombosis in ovarian hyperstimulation syndrome].
AB  - Ovarian hyperstimulation syndrome is an iatrogenic complication of controlled
      ovarian hyperstimulation. Its features are excessive growth of the ovaries and
      leakage of fluid from the intravascular space with ascites, hypovolemia and
      electrolyte imbalance, inducing a state of hypercoagulability, which can cause
      arterial or venous thrombosis. Thromboembolic events are the less common
      complications but they are the most serious. We communicate the case of a 30
      years old woman with history of primary infertility; she was in treatment with
      controlled ovarian hyperstimulation. The patient developed ovarian
      hyperstimulation syndrome and arterial thrombosis in the right femoral artery.

PMID- 21966798
TI  - [Preeclampsy and eclampsia. 1956].

PMID- 21966799
TI  - [The tenth anniversary of Gynecology and Obstetrics of Mexico. 1956].

PMID- 21966800
TI  - [Development of the teaching of gynecology and obstetrics in Mexico. 1956].

PMID- 21966801
TI  - [The teaching of gynecology and obstetrics at the Military Medical School].

PMID- 21966802
TI  - [The teaching of gynecology in Monterrey, NL, Mexico].

PMID- 21966803
TI  - [Contribution of the Society of Gynaecology and Obstetrics of Monterrey to the
      development of gynecology and obstetrics in the North of the Republic during the
      last ten years. 1956].

PMID- 21966804
TI  - [Maternal complications and HELLP syndrome].
AB  - BACKGROUND: HELLP syndrome is associated with more serious cases of preeclampsia
      eclampsia with a high frequency of maternal complications. OBJECTIVE: To report
      the prevalence and type of maternal complications in patients with HELLP syndrome
      and to compare these with the recent literature. PATIENTS AND METHODS: A cross
      sectional study was carried out in patients with HELLP syndrome treated between
      July 1, 2009 and July 31, 2010 in the intensive care unit. Maternal complications
      were registered in the clinical files. Statistical descriptive measures
      (averages, median, and standard deviations) and T Student test were used for
      statistical analysis. RESULTS: Of a total of 297 patients with P-E, 11.44% (34
      cases) corresponded to HELLP syndrome. Prevalence of patients with HELLP syndrome
      and maternal complications was 35.29% (12 cases) as follows: class I: 16.66% (2
      cases), class II: 16.66% (2 cases), class III: 66.68% (8 cases). Average age of
      patients was 30 +/- 6.91 years and gestational age was 32.25 +/- 3.64 weeks.
      Cesarean section was carried out in 91.67% patients (11 cases). Maternal
      complications included the following: ascites, 21.06%; oligohydramnios, 21.066%;
      abruptio placentae, 10.53%; multiple organ failure, 10.53%; nosocomial pneumonia,
      5.26%; sepsis, 5.26%; acute renal insufficiency, 5.26%; uterine atony, 5.26%;
      polyhydramnios, 5.26%; eclampsia, 2.94%; placentae senescence 5.26%. There were
      no maternal deaths. CONCLUSIONS: Frequency of maternal complications was low.
      Types and distribution were different in relation to those reported in the
      international literature.

PMID- 21966805
TI  - [Probable association between preeclampsia/eclampsia and paternal age: a pilot
      study].
AB  - BACKGROUND: The preeclampsia is a multisystemic syndrome that occupied the first
      cause of maternal and fetal mortality around the world. Epidemiologic studies
      shown both mother and father contribute at the same risk for preeclampsia.
      OBJECTIVE: To determinate if there is an association between preeclampsia and
      paternal age. MATERIAL AND METHOD: Preeclampsia-eclampsia patients and couples
      were analyzed in agree to "National High Blood Pressure Education Program Working
      Group" classification, and a control group constituted by normal pregnant women
      and couples was included. RESULTS: There were 27 cases with mild preeclampsia and
      her couples, 13 cases with severe preeclampsia and her couples and 40 controls
      conformed by normal pregnant women and her couples. The statistical analysis of
      variance of the ages shown that men from preeclamptic group had a greater
      variance in contrast with man of control group (p < 0.001; valor of F = 5.084).
      CONCLUSIONS: Although is not clear how paternal age interview in preeclampsia
      risk, the interaction between paternal-maternal imprinting and spermatic
      senescence, followed by shortened telomeres of chromosome, could be produce the
      inactivity of a whole network of signals implicated in disease aetiology.

PMID- 21966806
TI  - [Evaluation of two transfer embryo systems performed by six physicians].
AB  - BACKGROUND: Embryo transfer is a critical point for success in IVF cycles. Many
      factors should be considered when performing an embryo transfer such as: embryo
      quality and number, soft versus rigid catheter, easy of the transfer, physician
      technique, ultrasound guide during transfer, among others. OBJECTIVE: Evaluate
      two different embryo transfer systems performed by six physicians with the same
      protocol. MATERIAL AND METHODS: We evaluated 308 embryo transfers performed from
      January 2006 to December 2008 by six physicians with two different systems. We
      only included patients with good quality in embryos and endometrium. Both systems
      were analyzed in each of the six physicians. RESULTS: Similar characteristics in
      number of transferred embryos, number of cells in each embryo and quality of
      them, were found in both groups. There were no significant differences between
      both systems in the characteristics of the couple nor the mentioned above. Most
      of the transfers n = 252 (81.81%), were realized by two of the six physicians,
      however, the pregnancy rate did not show significant differences between these
      physicians and the less experienced ones. CONCLUSIONS: With the obtained results,
      it could be supposed that the most influential factor in the outcome is the
      operator experience in the use of each system and not the system itself.

PMID- 21966807
TI  - [Laparoscopic cholecystectomy in pregnancy. Five years experience at the Spanish
      Hospital of Mexico and literature review].
AB  - BACKGROUND: Biliary pathology is the second cause of abdominal acute pain during
      pregnancy. The surgical approach most often used for the treatment of acute
      cholecystitis during pregnancy is laparoscopy. Some aspects have made this
      approach during pregnancy controversial. OBJECTIVES: To analyze the maternal
      fetal benefits and complications of laparoscopic cholecystectomy during pregnancy
      and compare these results with the medical literature. MATERIAL AND METHODS: It
      is a retrospective, transverse study. Laparoscopic cholecystectomy cases and
      pregnancy from 2005 to 2009 at Hospital Espanol de Mexico city were reviewed. The
      following information was obtained: maternal age, gestational age, signs and
      symptoms, medical department that made the diagnosis, the laparoscopic entry
      techniques, the monitoring of CO2 for the pressure of pneumoperitoneum, the
      complications in the peri and postoperatory state, the use of tocolytics
      medication and other medicines in the hospital stay, maternal and perinatal morbi
      morbility, days of hospitable stay, follow-up surgical postintervention in the
      office. We did a comparation of our results with the medical literature. RESULTS:
      10 laparoscopic cholecystectomies were performed. Gestational ages were from 15
      to 25 weeks. The incidence was 1:995. All the cases were diagnosed by doctors of
      the department of general surgery, and also the surgeries. 2/10 patients were in
      preterm delivery risk at 35 weeks of gestation. There was not any fetal loss or
      maternal death. CONCLUSIONS: Our results are similar with the literature
      research, and we confirm that laparoscopic cholecystectomy is a safe therapeutic
      option for gravid patients, which has minimal fetal-maternal morbidity.

PMID- 21966808
TI  - [Elective caesarean: impact of evolution neonatal respiration].
AB  - The number of Caesarean births has increased worldwide. Respiratory distress
      syndrome is associated with caesarean delivery, especially in the absence of
      labor. During the latter stages of pregnancy physiologic changes occur that are
      accelerated with the onset of labor, which is accompanied by changes in hormones
      and mediators in the mother and fetus. An acceleration in the evacuation of lung
      liquid is held in this period, largely dependent sodium channels sensitive to
      amiloride than are found in the alveolar epithelium. The failure of these
      mechanisms can lead to newborn severe respiratory difficulty and require
      intensive care, mechanical ventilation and surfactant. We need to develop
      preventive and therapeutic strategies to improve outcomes in this vulnerable
      population.

PMID- 21966809
TI  - [Human papillomavirus infection and adolescence].
AB  - Infection with human papillomavirus has increased dramatically in recent years.
      The highest prevalence rates are among adolescents and young women, reflecting
      changes in sexual behavior associated with biological factors in adolescent
      development. Adolescents who begin sexual activity early are at greater risk of
      precursor lesions and cervical cancer. There are adolescents with special
      circumstances, where no early decision should be delayed cervical cytology and in
      whom it is important to initiate consultations and periodic reviews with a
      preventive approach. Cervical cancer can be avoided when the diagnosis and
      treatment of precursor lesions is early. Despite efforts at sex education based
      on "safe sex" with the correct use of condoms has not been able to reduce the
      incidence of infections with human papillomavirus in adolescents. While better
      than nothing, condom use is not 100% reliable. Studies show that consistent and
      correct use provides protection against the human papillomavirus only 70%. In
      Mexico, reported an overall ratio of actual use of condoms from 24.6%. It is
      clear that the physician who provides care for adolescents plays a fundamental
      role in sex education. The key to future prevention of cervical cancer and its
      precursor lesions could be the vaccination.

PMID- 21966810
TI  - [Pituitary tumor detected prenatally].
AB  - INTRODUCTION: Brain tumors are present in 2.9 per 100,000 newborn.
      Craniopharyngioma is a benign and slow growing brain tumor, frequently localized
      in the sellar and suprasellar region. There are few reports of pituitary tumor
      detected prenatally. CASE REPORT: We report a neonate with a craniopharyngioma
      detected prenatally as a pituitary tumor. In a 23 year old mother, second
      gestation, with no important history, was detected a sellar tumor at 31 gestation
      weeks, the obstetric ultrasound reported a suprasellar tumor of 2 per 3 cm
      diameter. Pregnancy ended in a vaginal delivery at 39 weeks, and obtained a 3.9
      kg female, with cephalic diameter of 37.5 cm, the Apgar score was 8-9 at 1st and
      5th minutes. In early neonatal period was scanned and confirmed a 3.2/2.3/2.9 cm
      suprasellar tumor with calcium deposits. The Paediatric Oncology department
      suggested a surgery and was realized a craniotomy at 3rd week of age. The surgery
      allowed to obtain 30% of the tumor and confirmed by histology craniopharyngioma.
      Patient had favourable evolution and was discharged at 3 months of age.
      CONCLUSIONS: We report a neonate in who was detected by prenatal ultrasound the
      presence of a suprasellar solid tumor, scan and magnetic resonance images in
      neonatal period defined its size and location and a craniopharyngioma was
      confirmed by histology. Patient had a satisfactory postsurgical evolution and was
      discharged at 3 months of age.

PMID- 21966811
TI  - [Case report. Post cesarean section laparoscopic cholecystectomy for
      hydrocholecystitis].
AB  - BACKGROUND: Acute cholecystitis is the second most common surgical emergency in
      pregnant women. Although laparoscopic cholecystectomy has been described
      previously in these cases, there is still controversy regarding the most
      appropriate moment in which to perform the procedure. OBJECTIVE: To describe the
      clinical presentation and management of a female with 36.6 weeks of pregnancy and
      clinical signs of acute cholecystitis. Cesarean section to deliver a healthy
      newborn was immediately followed by laparoscopic cholecystectomy without
      complications. A 10 year literature review complements the analysis and
      discussion of the case. CLINICAL CASE: A 33 year-old female with 36.6 weeks of
      gestation presented a history of 24 hours with right upper quadrant and
      epigastric abdominal pain, nausea and vomiting. Symptoms were precipitated by
      cholecystokinetics and did not subside after expectant and pharmacologic medical
      treatment. The medical group decided with the patient's consent to interrupt the
      pregnancy via Cesarean section immediately followed by laparoscopic
      cholecystectomy. RESULTS: After Cesarean section through a Pfannenstiel incision,
      laparoscopic trocars were placed and cholecystectomy performed without
      complications. The postsurgical course was favorable and both patient and newborn
      were discharged on day four. CONCLUSIONS: Laparoscopic surgery cholecystectomy
      during pregnancy and in the immediate puerperium is feasible and safe. These
      combined procedures: rapid pregnancy interruption followed by a minimal invasive
      approach gives the benefits of laparoscopic surgery in these patients.

PMID- 21966812
TI  - [Giant ovarian cyst and pregnancy. Case report and literature review].
AB  - Ovarian tumors represent approximately 30% of genital tumors, being the most
      frequent the germ and the epithelial tumors. During pregnancy the incidence of
      ovarian cysts is less than 5%, and they are almost always benign. Giant cysts
      have a frequency of less than 1%. A giant cyst in a primigravida 20 years, 15
      weeks pregnant and the evolution of the same case is reported.

PMID- 21966813
TI  - [Concept and integration of the specialized gynecological laboratory, their
      utility and recent progress in this field. 1956].

PMID- 21966814
TI  - [Perinatal complications in patients with chronic renal failure].
AB  - BACKGROUND: Pregnant patients with chronic renal insufficiency (CRI) have a high
      risk of perinatal complications and deterioration of renal filtration (RF).
      OBJECTIVE: To report perinatal complications and changes of RF according to
      disease severity. MATERIAL AND METHOD: Cross-sectional study including 28
      pregnant patients grouped into three categories of CRI according to initial
      creatinine (Cr): mild CRI < 1.5, moderate CRI 1.5-2.5 and severe CRI > 2.5 mg/dL.
      Pre-labor vs initial perinatal complications and changes in endogenous creatinine
      clearance (CrCI) were reported. Descriptive statistics and Student t-test were
      used for statistical analyses. RESULTS: Mild CRI was found in 50%, moderate in
      35.72% and severe in 14.28% of patients. Maternal complications were as follows.
      Mild CRI: Cesarean (35.72%), deterioration of RF (21.42%) and worsening of
      systemic arterial hypertension (SAH) (7.14%); moderate CRI: Cesarean (28.57%),
      deterioration of RF (28.57%) and worsening of SAH (14.28%); severe CRI: Cesarean
      (14.28%), deterioration of RF (14.28%) and anemia (14.28%). Fetal complications
      were as follows. Mild CRI: prematurity (25%), fetal growth restriction (FGR)
      (7.14%) and fetal death (7.14%), moderate CRI: prematurity (21.42%), FGR (3.57%)
      and no reassuring fetal status (NRFS) (3.57%), severe CRI: prematurity (14.28%),
      NRFS (7.14%) and respiratory insufficiency (7.14%). Mild CRI showed a reduction
      of endogenous CrCI (p = 0.03) not shown in other categories. CONCLUSION: An
      elevated frequency of complications was found, with the most serious occurring in
      patients with severe CRI. Deterioration of RF was found in patients with mild
      CRI.

PMID- 21966816
TI  - [Intrauterine insemination results in the Specialized Center for Women's Care].
AB  - BACKGROUND: intrauterine insemination should be offered to couples with
      unexplained infertility, given its effectiveness and compared to in vitro
      fertilization and embryo transfer, is less invasive and requires less resources.
      It also should be offered to couples with male factor infertility in selected
      patients with induction of ovulation to increase the chances of pregnancy.
      OBJECTIVE: to determine the rate of pregnancy with intrauterine insemination in
      couples with infertility. MATERIAL AND METHODS: descriptive and retrospective
      study of 500 couples with female, male and combined infertility, primary or
      secondary, managed with homologous insemination, with controlled ovarian
      stimulation and programmed ovulation, in patients with at least one permeable
      salpinx, FSH <12 IU/L and > 5 x 10(6) mobile and normal sperm. Ultrasonografic
      follicular follow-up and ovulation triggering according to findings, performing
      insemination 36 hours after the shooting, with luteal phase support with
      progesterone. RESULTS: 1.6 cycles on average, female infertility 65.8%, 21% male
      and combined 13.2%, age average 32 years of women and 36 years of man, average
      ovarian stimulation 8 days. Pregnancy in 19.5% of the patients, of these, 65.1%
      under the age of 35 years, 33.3% from 35 to 40 years and 1.5% older than 40
      years. Pregnancy at term 77.08%, miscarriage 11.45% and unknown resolution at
      11.45%. Twin pregnancy 14.61% and high fetal order 5.7%. Pregnancy with female
      infertility 64%, male 22.3% and combined 13.5%. Pregnancy with endometrial <8 mm
      9.8%, 8-15 mm 86.4% >15 mm 3.6%. With trilaminar endometrium 72.3%, dense 12.5%,
      linear 0.5%. CONCLUSION: The rate of pregnancy in intrauterine insemination
      hardly exceeds 20%. The determinants for this are the women age, type of
      infertility and endometrial characteristics. It was also noted high twin
      pregnancy and high fetal order.

PMID- 21966815
TI  - [Placental villous lesions in HIV-1 infection treated with zidovudine].
AB  - BACKGROUND: HIV-1 reaches the placenta through the maternal-fetal transmission
      from an infected uterus. This virus has cytolytic capabilities. The placenta in
      its maturation process has regressive or degenerative changes within certain
      limits, are considered normal. However, factors such as virus and
      antiretrovirals, can increase the proportion of these lesions. OBJECTIVE: To
      evaluate morphological changes in placental villi of pregnant women infected with
      HIV-1 treated with AZT. MATERIAL AND METHODS: descriptive, prospective,
      comparative, with non-probability sampling of observations in villi as units of
      analysis of the placentas from the group of patients with HIV-1 infection and
      zidovudine regimen and of the control group of four placentas from HIV negative
      patients. Both groups in the last trimester of pregnancy. H-E staining was used
      in 25 films from five placental regions of the study group and four from the
      control group, using a protocol of 6 variables identifying syncytial knots,
      fibrinoid changes, villous edema, stromal fibrosis, calcification and villous
      immaturity. Observations were analyzed using ANOVA as a 2 x 5 factorial
      arrangement with 4 replications subsampling and split plot design and Tukey test.
      RESULTS: Chorionic villi showed percentages of alterations that exceed the normal
      range. It showed significant differences (p<0.05) between the placentas exposed
      to HIV-1 and AZT and normal placentas in relation to the percentage of villi
      affected by 5 variables, except fibrosis. CONCLUSIONS: The lesions may be
      increasing the vertical transmission of HIV-1. We also found evidence that the
      placenta is not in the best conditions for the transfer of gases, nutrients and
      metabolites, which could promote a decrease in birth weight and placental weight.

PMID- 21966817
TI  - [Comparison of isosorbide dinitrate and dinoprostone for induction of labor in
      term pregnancy].
AB  - BACKGROUND: it has been suggested that nitric oxide generators, such as
      isosorbide dinitrate, may be an alternative to mimic the effects of signal
      transduction mechanisms leading to cervical ripening, without affecting uterine
      contractility. OBJECTIVE: to compare the isosorbide dinitrate and dinoprostone
      for induction of labor in term pregnancy. MATERIAL AND METHODS: in a randomized
      controlled blinded clinical trial, we studied 66 patients divided into 2 groups:
      33 patients were given 20 mg of isosorbide dinitrate and to the other 33 were
      administered 0.5 mcg of dinoprostone; in both groups the drugs were administered
      vaginally each 6 h and at maximum 3 times. It was carried out a cardiotocographic
      study in order to determine the presence or absence of uterine activity and to
      exclude disorders of the fetal heart frequency; it was performed a vaginal
      examination to assess cervical conditions determining the Bishop score at 0, 6
      and 12 h. RESULTS: there were no differences between the groups in the
      determinations of mean arterial pressure, maternal heart frequency, fetal heart
      frequency and Bishop score registered at 6 y 12 h followed the drugs
      administration. The time of delivery was 20.7 +/- 1.8 h in the group of women
      treated with dinoprostone; and 16.3 +/- 1.4 h in women treated with isosorbide
      dinitrate (p=0.032). The cost was higher in women treated with dinoprostone ($560
      vs $12, respectively, p=0.001). There was no difference between the groups
      related to: frequency of meconium stained liquid (p=1.000), mode of delivery by
      caesarean section (p=0.918), Apgar score at 1 minute (p=0.764) and 5 minutes
      (p=0.294) and mother discharged with healthy baby (p=1.000). CONCLUSIONS: the
      isosorbide dinitrate is associated with lower duration of labor compared with
      dinoprostone. There was no difference in the maternal-fetal outcome by using
      whatever drug.

PMID- 21966819
TI  - [A surgical alternative for placenta accreta].
AB  - The placenta accreta is the second leading cause of obstetric hemorrhage in the
      world. In many occasions it is necessary to make an obstetric hysterectomy, a
      circumstance that increases morbidity, and maternal mortality. Communicates a
      surgical alternative to hysterectomy obstetric that has enabled us to reduce
      until the time to zero our rate of maternal deaths by obstetric hemorrhage, in
      addition to reducing the surgical time and the associated morbidity, without
      changing the perinatal outcome.

PMID- 21966818
TI  - [Role of uric acid in preeclampsia-eclampsia].
AB  - Uric acid is a terminal metabolite of the degradation of nucleotides, which
      increases their blood levels in patients with preeclampsia-eclampsia, increasing
      its synthesis by damage and death of trophoblastic cells in proliferation and
      decreased urinary excretion due a lower glomerular filtration rate and increased
      absorption in the proximal tubule. Hyperuricemia (> 4.5 mg/dL) is the first
      biomarker of the clinical chemistry considered as an early evidence of disease (<
      or = 20 weeks gestation). Uric acid concentrations are not only a criterion for
      establishing the correct diagnosis and the differential with other hypertensive
      states, but an indication of termination of pregnancy, often by cesarean section.
      Hyperuricemia has also demonstrated its usefulness as a predictor of maternal and
      fetal complications and maternal sequelae of late postpartum. Several studies
      have demonstrated its influence on the genesis of preeclampsia-eclampsia, either
      alone or jointly with other known processes (metabolic syndrome, oxidative
      stress, inflammation cascade, angiogenesis) that have a proven role in
      perpetuating the endothelial damage and maternal vascular smooth muscle cells.
      Further research is needed in large-scale clinical and experimental studies that
      expand our knowledge about the usefulness of uric acid as a biomarker of
      preeclampsia-eclampsia to allow early prevention and reducing the prevalence.

PMID- 21966820
TI  - [Diagnosis of premature menopause measuring circulating anti-Mullerian hormone].
AB  - The production of anti-mullerian hormone for the ovarian follicles begins near
      the puberty and the circulating levels begin to descend progressively in the
      stage of the pre-menopause coinciding with the depletion follicular and in
      consequence the menstrual cycles become irregular, frequently anovulatories.
      Therefore, concentration of anti-mullerian hormone shows a close correlation with
      follicular reserve and reproductive capacity, more than FSH and estradiol
      measurements. We described two patients that developed premature ovarian failure
      without previous diagnosis and therefore just were treated pharmacologically with
      estrogen-progestagen to induce menstrual bleeding. In blood of both patients was
      found low levels (< or = 4 ng/mL) of anti-mullerian hormone, and by means of
      sonography the absence of follicles was demonstrated in the ovaries. Has intended
      that premature ovarian failure could be of a chromosomal dysfunction, similar to
      other gonadal dysgenesias, another explanation of the mechanism is that it could
      be for development of some autoimmunity dysfunction. Therefore, the combined
      hormonal substitution of estrogen with progestagen should stay during several
      years to avoid the complications for the lack of estrogens; in some cases, could
      be informed on offering the pregnancy possibility by means of the attended
      fertilization using ovules donor.

PMID- 21966821
TI  - [Transcesarean ileal resection of double Meckel diverticulum].
AB  - We report the case of Ileal resection, in a woman aged 27 during Kerr Caesarean
      section, we observe two ileum bag located at 20 and 40 cm, from the ileocecal
      valve, the farthest and largest containing air with breaking risk. Ileal surgical
      excision was performed with entero-entero anastomosis with silk sutures number
      00. Postoperative treatment: antibiotics for 7 days: amikacin 500 mg
      intravenously every 12 hours and ceftriaxone 1 g every 8 hours. Fasting for 5
      days diet progression to oral tolerance and normal bowel movements. Discharged
      from hospital on the seventh day after surgery in good condition. Medical
      examination at 7, 15 and 30 days without complications. Pathological report of 2
      Meckel diverticulum without ectopic tissue.

PMID- 21966822
TI  - [Fetus compressus and fetus papyraceous. Clinical differences (report of three
      cases)].
AB  - The items papyraceus fetus and fetus compressus are used like synonymous. The low
      incidence and the lack of reporting of these cases leads to confusion. Clinical
      evidence shows significant differences between them and sustain a proper
      diagnosis. We report 3 cases of patients with multiple pregnancy (2 twins and 1
      triplets) observed in the death of one of the products of each patient, obtaining
      2 fetus compressus and 1 fetus papyraceous, respectively.

PMID- 21966823
TI  - [Obstetric analgesia. Personal experience (current events on analgesia and
      anesthesia in labor).1956].

PMID- 21966824
TI  - [Fetal fibronectin and cervical length as early predictors of preterm labor].
AB  - BACGROUND: preterm birth is a major obstetric problem that contributes to 70% of
      perinatal mortality. OBJECTIVE: to determine the sensitivity, specificity and
      predictive values of fetal fibronectin and cervical length as predictors of
      preterm birth in the HGR No. 36, Puebla. MATERIAL AND METHODS: observational,
      prospective. comparative study. Pregnant women were included between 24 and 33
      weeks amenorrhea and diagnosis of preterm labor. Quik Chek Kit was used to detect
      fibronectin using qualitative methods, and then subjected to measurement of
      cervical length with endovaginal ultrasound. Patients with a positive result or
      both proceeded to start treatment. To calculate sensitivity, specificity and
      predictive values were used odds ratios and Fisher exact test for statistical
      analysis. RESULTS: of 66 patients 34% reported positive fibronectin with a
      sensitivity and PPV of 92% and 77% compared with the assessment of 27% of
      patients with short cervical length at 55% and 88% respectively. 28% had two
      positive marker (fibronectin/cervical length), the sensitivity, specificity and
      positive and negative predictive values increased significantly (86%, 100%, 93%,
      100%). The average time between birth positive test was observed at 21 days. Risk
      factors for preterm delivery were found: patients under 25 years (P:0.0009),
      primigravida (P:0.0057), genitourinary infection (P:0.0001). CONCLUSION: the
      double marker fibronectin / cervical length is useful for determining patients at
      risk of preterm delivery because of its high specificity and NPV, ideal for easy
      handling and low cost.

PMID- 21966825
TI  - [Influenza H1N1 in obstetric population of a general hospital in Oaxaca].
AB  - BACKGROUND: In April 2009 are reported the first cases of H1N1 influenza in
      Mexico, presenting the first death from this cause in the city of Oaxaca in the
      same month. Different epidemiological reports of pandemics brought to the
      pregnant and high risk population for complications secondary to infection with
      influenza H1N1 due to immune status. OBJECTIVE: describe the obstetric population
      infected with H1N1 influenza in the Hospital General Dr. Aurelio Valdivieso of
      Oaxaca. MATERIAL AND METHOD: Retrospective and observational study conducted in
      pregnant women with suspected infection by the virus of the influenza A/H1N1
      served in the General Hospital Aurelio Valdivieso of Oaxaca, Oax in 13 patients
      with influenza H1N1 confirmed by RT-PCR during the pandemic occurred from May
      2009 to April 2010. RESULTS: We reported 27 suspected cases of H1N1 influenza in
      pregnant women of which 13 were positive by RT-PCR, the cumulative incidence was
      1.6 per 1000 pregnant women during the period. The fatality rate was 7.6 per
      hundred pregnant women affected, one case of maternal death indirectly by fluid
      and electrolyte imbalance occurred and the attack rate was 0.16 per 100 pregnant
      women, the main complication of atypical pneumonia occurred in four cases
      followed by three cases of preeclampsia, infants showed no defects and perinatal
      outcomes were good to present two cases of admission to the NICU for iatrogenic
      prematurity without deaths. CONCLUSIONS: H1N1 influenza infection has a high
      fatality rate in late pregnancy. Perinatal outcomes did not worsen the condition
      or management.

PMID- 21966826
TI  - [Analysis and perinatal outcome after intravascular transfusion].
AB  - INTRODUCTION: the leading cause of fetal anemia is Rh isoimmunization. The timely
      diagnosis by ultrasound and intravascular transfusion improves the prognosis.
      OBJECTIVE: to evaluate the increase in hemoglobin in the fetus and correlate the
      red cell transfusion volume with elevation of hemoglobin and perinatal outcome.
      PATIENTS AND METHODS: prospective, case series study. We included 17 patients
      with fetal anemia detected by measuring the peak systolic velocity of middle
      cerebral artery and determination of fetal hemoglobin before and after
      cordocentesis. After confirmation of fetal anemia (Hb <10 g/dL), was held fetal
      transfusion with 50 mL/kg estimated fetal weight, with packed red blood cells
      type O Rh negative. RESULTS: In 17 cases fetal anemia was diagnosed, of which 11
      (64%) had Rh isoimmunization and 6 (36%) were not immune. The 17 cases received
      27 intravascular transfusions, in 75% hemoglobin rose to 10 g/dL, 45% in the
      first transfusion, 25% in the second and 10% in the third transfusion. Fetal
      hemoglobin between before and after transfusion was 6.5 and 12.9 g/dl,
      respectively (p<0.001) and allowed to continue the pregnancy from 3 to 12 weeks
      from the first transfusion. There were 4 deaths (2 stillbirths and 2 neonatal),
      but only one was related to the procedure. the survival rate was 76%, mortality
      in the presence of hydrops was 30% and no deaths in patients without hydrops.
      CONCLUSIONS: Mortality in fetal anemia was 23.6% and only one case was related to
      intravascular transfusion. In cases of survival to birth, pregnancy lasted >30
      weeks gestation. Hemoglobin rose from 27 to 300% of the initial fetal hemoglobin.
      The presence of fetal hydrops significantly increases mortality.

PMID- 21966827
TI  - [Reduction of maternal mortality in San Luis Potosi].
AB  - BACKGROUND: Maternal mortality is a public health problem reflecting lack of
      infrastructure in health facilities or poor obstetrical training of those caring
      for pregnant women. OBJECTIVE: To report the results of a comprehensive program
      of the Health System of San Luis Potosi State, aimed at reducing maternal
      mortality in the period 2004-2008. MATERIAL AND METHODS: An observational and
      retrospective study based on information provided by the State Committee for the
      Study and Prevention of Maternal Mortality in the 58 municipalities, hospitals
      and medical units of the state of San Luis Potosi. RESULTS: During the period
      2004-2008, maternal mortality was reduced by 55% as a result of increased
      postpartum contraception coverage from 32 to 74% in general and community
      hospitals, and from 47 to 58% in health care units located in risk areas. In
      2004, births fell by 5.8%. Between 1990 and 2003, 2,929 newborns were left
      maternal orphans, with an annual average of 209. During the study period, 423
      infants were in the same situation, with an average of 70. CONCLUSIONS: The
      present conditions of the social environment of San Luis Potosi are favourable to
      further reduce maternal mortality.

PMID- 21966828
TI  - [Caesarean section for cephalo-pelvic disproportion performed without evidence.
      Does the radiological pelvimetry has a place in obstetrics today?].

PMID- 21966829
TI  - [Idiopathic granulomatous mastitis treated with steroids and methotrexate].
AB  - Idiopathic granulomatous mastitis is a rare inflammatory breast disease of
      unknown etiology. It manifests as breast mass of 6 cm on average (range 2-10 cm),
      often in upper outer quadrant of left breast, in another quadrant, right or
      bilateral breast. Clinical diagnosis by ultrasound or mammography and fine needle
      aspiration confuses with carcinoma; histopathology (gold standard) confirm the
      diagnosis after ruling out causes of granulomatous inflammation, mainly
      tuberculosis. Steroid treatment achieve complete remission, but adverse reactions
      and relapses after the descent and suspension. Methotrexate or azathioprine is
      added from the start to maintain remission. We report three cases of idiopathic
      granulomatous mastitis diagnosis and treatment based on prednisone until clinical
      improvement and methotrexate as maintenance therapy. Complete remission was
      obtained in three patients. The rheumatologist knows and handles
      autoimmune/inflammatory with these drugs, therefore, is suggested the
      multidisciplinary treatment of this disease with oncologists and gynecologists.

PMID- 21966830
TI  - [Spontaneous heterotopic pregnancy. Case report].
AB  - BACKGROUND: Heterotopic pregnancy has increased in frequency due to the
      increasing number of assisted reproductive procedures. The diagnosis is difficult
      even with ultrasonography. OBJECTIVE: To report the case of a patient with
      heterotopic pregnancy without a history of in vitro fertilization or fertility
      treatment. CONCLUSIONS: Heterotopic pregnancy is a rarity that requires a high
      diagnostic suspicion, specialized desk studies and early surgical care to ensure
      a favorable outcome to the embryo.

PMID- 21966831
TI  - [Vulvar leiomyoma. Report of a case].
AB  - We report the case of a 44-year-old, who was resected of a vulvar tumor. The
      pathological report was leiomyoma with focal myxoid degeneration, which is an
      infrequent benign tumor.

PMID- 21966833
TI  - [Considerations on some aspects of ectopic pregnancy. Analysis of 50 cases
      operated. 1956].

PMID- 21966832
TI  - [Urethral myomas: report of two cases and literature review].
AB  - Leiomyomas of the bladder and urethra are extremely rare. Depending on their
      location and size, they can produce diverse clinical manifestations. At urethral
      level in particular, formed near the vaginal wall, symptoms include recurrent
      urinary tract infections, voiding dysfunction, foreign body sensation, heaviness
      and dyspareunia. We present two cases of urethral leiomyomas, one expressed
      during pregnancy, which resolved successfully with surgical resection without
      damage to the urinary tract and no recurrence so far.

PMID- 21966834
TI  - [Comparison of maternal and perinatal outcomes in the conservative treatment
      preterm premature membrane rupture between the use of erythromycin and
      clindamycin].
AB  - BACKGROUND: premature rupture of membranes occurs between 5 and 15% of
      pregnancies, of these, 10% occurs at term and preterm 2 to 3.5%. OBJECTIVE: To
      compare maternal and perinatal outcomes from the use of erythromycin or
      clindamycin in women with preterm premature rupture of membranes with
      conservative treatment at the Regional General Hospital No. 36. PATIENTS AND
      METHODS: comparative, prospective, randomized study conducted at the Regional
      General Hospital No. 36 of the Instituto Mexicano del Seguro Social, Puebla. The
      most common risk factors were cervical infections (55%) and urinary tract
      infection (55%). A history of premature rupture of membranes in pregnancy was
      reported in 12.5% of patients. Group A was prescribed erythromycin and group B,
      standard-dose clindamycin, these were the independent variables. Maternal
      outcomes (deciduoendometritis and chorioamnionitis) and perinatal (respiratory
      distress syndrome, necrotizing enterocolitis and sepsis) were the dependent
      variables. Fisher exact test was applied to the results of the study. RESULTS:
      about perinatal outcome, sepsis was expressed more frequently in the clindamycin
      group (60%) compared with erythromycin (35%). The occurrence of respiratory
      distress syndrome was similar in both groups, 70 and 75% respectively. For
      necrotizing enterocolitis, 25 and 5%. Maternal alterations as chorioamnionitis
      occurred in 20% of patients in group A and 5% in group B. Endometritis results
      were similar in both groups. CONCLUSIONS: comparing the maternal and perinatal
      outcomes with conservative management of premature rupture of membranes, results
      were better in the group treated with erythromycin. It is not possible to prove
      it statistically because of the sample size.

PMID- 21966835
TI  - [Perinatal outcomes of patients with gestational diabetes diagnosed by three
      different methods].
AB  - BACKGROUND: Gestational diabetes is one of the most common diseases during
      pregnancy. Despite this situation, there is still no consensus on methods for
      screening and diagnosis of this disease. OBJECTIVE: To assess perinatal outcomes
      of patients with gestational diabetes diagnosed using three different methods.
      PATIENTS AND METHODS: Clinical observational, longitudinal, randomized trial at
      the National Institute of Perinatology Isidro Espinosa de los Reyes. We included
      all patients admitted to the Institute for a period of three months without
      pregestational diabetes. Patients were screened for gestational diabetes with an
      oral load of 50 g of glucose. Patients with a positive screen were randomized by
      a computer program that randomly chose patients and made a curve according to the
      criteria of the American Diabetes Association 75 g or 100 g and another group
      with 75 g according to the criteria of the World Health Organization. Patients
      with gestational diabetes were followed throughout pregnancy until its
      reclassification in the puerperium. RESULTS: Screening was performed in 863
      patients and 87 were diagnosed with gestational diabetes. Perinatal outcomes were
      similar in patients with gestational diabetes diagnosed using different methods,
      but there was a higher frequency of pregnancy-induced hypertension in patients
      diagnosed with the curves of the American Diabetes Association 75 and 100 g
      compared with the curve of the World Health Organization. CONCLUSIONS: The
      American Diabetes Association diagnostic method as the World Health Organization
      are acceptable forms to diagnose gestational diabetes.

PMID- 21966836
TI  - [Carbetocin use to prevent obstetric hemorrhage].
AB  - BACKGROUND: in Mexico, obstetric hemorrhage and its complications are the second
      leading cause of maternal death and is the origin of irreversible functional
      consequences. Carbetocin is a synthetic analogue of oxytocin with an average
      lifespan four times that of oxytocin and pharmacological effects of 120 minutes
      produces a tonic contraction which reduces postpartum blood loss. OBJECTIVE: To
      evaluate the usefulness of carbetocin to prevent uterine bleeding complications
      and maternal deaths and assess the benefits, effectiveness and side effects.
      PATIENTS AND METHODS: Prospective, observational clinical research in two phases,
      the first from May 2005 to January 2006 with a sample of 40 patients and the
      second from January to December of 2008 with a sample of 72 patients conducted at
      the Hospital Materno Infantil Dr. Alberto Lopez Hermosa, San Luis Potosi. All
      were high-risk pregnancies and medical complications that warranted specialty
      hospital management. The intervention consisted of applying undiluted single dose
      of 100 micrograms of intravenous carbetocin at the time of delivery, as
      prophylaxis in patients with uterine overdistention in the first phase of the
      study and complicated pregnancies in the second phase. RESULTS: Were born by
      caesarean section over 60%. Initially, the hemoglobin showed a reduction of 17%
      after delivery. Seven patients required blood transfusion (17.5%). In the second
      phase, 65 patients (90%) did not require transfusion, only 6 patients (8%)
      required transfusion. No side effects were documented. Uterine overdistension was
      the main risk factor for bleeding and transfusion. CONCLUSIONS: Carbetocin
      combines the safety of oxytocin and the strength of the ergonovine preparations.
      To determine where carbetocin will be situated in the future as an useful
      oxytocic, it requires more than a simple demonstration of its effectiveness. This
      should be determined in each clinical situation, with factors such as
      overdistended uterus, indicating the convenience and economic constraints.

PMID- 21966837
TI  - [Fetal acardia in a twin pregnancy achieved by in vitro fertilization].
AB  - The frequency of fetal arcadia in the world is 1:35,000 to 1:48,000 pregnancies;
      is currently estimated that 1% of newborns in developed countries are the result
      of assisted reproduction techniques and the frequency of twin pregnancies is
      close to 18%, of these, an estimated relative risk for cardiac defect is 1.6.
      However, the association of acardiac fetus, twin pregnancy and assisted
      reproductive techniques is not fully established. In this paper, we describe a
      case of fetal acardia, in a pregnancy resulting from assisted reproduction and
      its obstetric care.

PMID- 21966838
TI  - [Partial molar pregnancy. A case report and literature review].
AB  - We report the case of a 17 year old patient with partial molar pregnancy and
      coexistent live fetus of 13 gestational weeks diagnosed by ultrasound, which
      required the termination of pregnancy for maternal decompensation.

PMID- 21966839
TI  - [Resistant ovary syndrome. Case report].
AB  - Patients with primary amenorrhea, sexual infantilism and elevated pituitary
      gonadotropins are frequently diagnosed with hypogonadism hypergonadotropic and
      suspected ovarian failure, secondary to a chromosomal abnormality, intrinsic
      ovarian failure or altered receptors for gonadotropins, mainly FSH (ovarian
      resistance). We report the case of a 16-year-old, admitted to the endocrinology
      clinic for primary amenorrhea and lack of development of secondary sexual
      characteristics. A complete physical examination revealed: height of 1.58 m and
      57 kg weight, with incipient breasts (Tanner I), sparse pubic and axillary hair
      (Tanner I). The ultrasound reported small uterus and ovaries. Laboratory studies
      reported high levels of FSH and LH, estradiol and testosterone levels before
      puberty, prolactin, TSH, T3 and T4 normal. Normal female karyotype. Diagnostic
      laparoscopy was performed which showed two ovarian slips; biopsy was taken and
      reported both abundant primordial follicles and spindle cell stroma without
      evidence of primary and antral follicles, which integrates the diagnosis of
      resistant ovary syndrome.

PMID- 21966840
TI  - [Transmural rectal endometriosis as a cause of chronic constipation. A case
      report and literature review].
AB  - The incidence of intestinal endometriosis is reported between 5.3 and 12% of
      cases and of these, between 70 and 93% are located in the rectum and sigmoid. We
      report the case of a 32-year-old with constipation and bloating and cramping pain
      during the last 2 years. The pain increased in frequency during the past 6
      months. From the data obtained from physical examination and imaging studies may
      be suspected pelvic endometriosis with infiltration of anterior rectal wall.
      Resection of the low anterior rectum with colo-rectal anastomosis was performed,
      with adequate surgical outcome and resolution of symptoms. In patients of
      childbearing age with abdominal or pelvic pain, constipation of recent onset or
      occlusive bowel, which may or may not be related to the menstrual cycle should be
      considered transmural infiltration by endometrial tissue.

PMID- 21966841
TI  - [Diffuse cavernous hemangioma of the uterus diagnosed during pregnancy. Case
      report].
AB  - We report the case of a pregnancy of 16 weeks with anemia and a presumptive
      diagnosis of partial mole. In secondary care this diagnosis was ruled out through
      ultrasonography and diffuse cysts were found in the myometrium. Spectral Doppler
      ultrasound showed no flow, but it could be observed with power angiography.
      Cesarean section was performed at 38 weeks and hysterectomy 24 hours after
      because of intra-abdominal hemorrhage. Power angiography, spectral Doppler and
      serum human chorionic gonadotropin are the most useful diagnostic tools in the
      differential diagnosis of diffuse cavernous hemangioma of the uterus. Postpartum
      hemorrhage is a likely complication.

PMID- 21966842
TI  - [Elective induction of labor at term. 1956].

PMID- 21966843
TI  - [Uterine leiomyomas during pregnancy and its impact on obstetric outcome].
AB  - BACKGROUND: The association of uterine leiomyoma and pregnancy is increasing due
      to the tendency of couples to delay first pregnancy after age 30. The risk of
      uterine fibroids is greater with advancing age of the woman. OBJECTIVE: To
      evaluate the impact of fibroids on the incidence of complications during
      pregnancy, labor and delivery. PATIENTS AND METHODS: We observed 65 pregnant
      patients with uterine fibroids and 165 pregnant patients without fibroids. Follow
      up ultrasound was performed at weeks 20 to 24, 30 to 32 and 36 to 40. We analyzed
      the following variables: threatened abortion, pregnancy loss, preterm birth,
      premature rupture of membranes, abnormal fetal presentation, mode of termination
      of pregnancy, uterine atony, postpartum hemorrhage and perinatal outcome.
      RESULTS: The frequency of threatened abortion, risk of pregnancy loss in the
      second trimester, preterm births, premature rupture of membranes and abnormal
      fetal presentation was significantly higher in patients with uterine fibroids
      compared to patients without fibroids. It was not demonstrated that fibroids grow
      during follow-up even, there was a trend toward reduction in size as pregnancy
      progressed and until its completion. No significant differences in the frequency
      of cesarean section between groups (52.3 vs. 47.9%, RR 1.09; 95% CI 0.82-1.45, p
      = 0.646). Uterine atony was more frequent in patients with fibroids than in
      patients without fibroids (12.3 vs 4.2%, RR = 2.9, 95% CI 1.2-7.6, p = 0.036).
      There were no differences in perinatal outcomes between the groups. CONCLUSIONS:
      Uterine fibroids increase the risk of complications during pregnancy and
      childbirth. Could not be demonstrated an increased risk of caesarean section.

PMID- 21966844
TI  - [Rating the quality of care offered to women who underwent hysterectomy].
AB  - BACKGROUND: In recent years emerged as a primary need, the evaluation of the
      services offered to get better quality in them. Health systems are subject to
      these assessments. OBJECTIVE: To assess the quality of care provided to patients
      who underwent hysterectomy, since the reference of the family physician, until
      discharge by the gynecologist. We analyzed the diagnostic results in the short
      and long-term, patient satisfaction and gynecologist satisfaction, regarding the
      conditions for offering services. PATIENTS AND METHOD: Retrospective study
      including 118 patients who underwent hysterectomy and were analyzed the following
      aspects: history, diagnoses and outcomes. Cross-sectional surveys were also
      conducted to obtain the satisfaction of patients and the physicians who performed
      the surgeries. RESULTS: The satisfaction of patients was confirmed, in contrast
      to the opinion of gynecologists who expressed dissatisfaction with the resources
      they have. There was discrepancy between diagnosis, planned surgery and the
      procedure performed, however, the clinical results were adequate. CONCLUSIONS: At
      present, any institution should periodically evaluate the services it provides to
      implement measures and procedures commensurate with their population and
      resources and invite users to participate in internal decision making and provide
      the opportunity to become an evaluator to generate a culture of self-improvement
      and continuous improvement in all involved.

PMID- 21966845
TI  - [Breast cancer in Mexican women under 40].
AB  - BACKGROUND: Breast cancer is the leading cause of death from malignancy in women.
      The incidence increases with age, but the relationship between age and survival
      of breast cancer patients is not well defined. It is observed that young women
      with breast cancer have patterns more aggressive biological. OBJECTIVE: To
      determine the frequency, sociodemographic, clinical and histopathological
      features of breast cancer in women under 40 years attending a specialist breast
      unit in Mexico City. PATIENTS AND METHOD: Transversal, descriptive and
      retrospective study of patients under 40 years of age with breast cancer treated
      between 2005 and 2010. RESULTS: 1430 cases were diagnosed with breast cancer five
      years with a mean age of 53.64 +/- 11.87 years (range 23 to 93 years), 142 cases
      were women under 40 years of age (10%). The auto-detection of a breast lump was
      the most frequent clinical manifestation (50%). CONCLUSION: The prevalence of
      clinical stage III in this age group suggests the difficulty of diagnosis, the
      high breast density, which is one factor limiting studies of screening with
      mammography, it diminishes their effectiveness in early detection of breast
      cancer.

PMID- 21966846
TI  - [Appendicular endometriosis as a cause of acute abdomen].
AB  - Endometriosis affects between 4 and 17% of women of reproductive age. The
      intestinal endometriosis affects 3 to 12% of women and is usually asymptomatic
      when it affects the subserosa or serosa; 0.7 to 2.5% of patients require surgical
      treatment for symptomatic lesions with diarrhea, constipation, pain and
      hematochezia. We report a case of a patient with appendiceal endometriosis in
      which the diagnosis was made during an emergency surgery and histopathology
      reported involvement of the muscle wall and serosa.

PMID- 21966847
TI  - [Prenatal diagnosis of isolated otocefalia. Usefulness of three-dimensional
      ultrasound].
AB  - Otocephaly is a rare and lethal congenital malformation characterized by the
      presence of agnathia, microstomia, aglossia and synotia. Despite its frequent
      association with severe malformations, diagnosis in the few published cases is
      usually made at III trimester. In this case, three-dimensional ultrasound scan
      was performed in a Chinese primigravida with no remarkable personal nor familiar
      history since mandible was difficulty visualized with two-dimensional sonography
      at 21 weeks of gestation. Multiplanar and rendering mode showed the typical
      cervicofacial features of otocephaly without associated malformations. After
      parental counselling, they opted for termination of pregnancy and necropsy
      confirmed our prenatal findings. Our case shows the usefulness of three
      dimensional ultrasound in assessing fetal cervicofacial pathology. Volumetric
      capture allows a delayed study of fetal anatomy and multiplanar mode offers the
      reconstruction of views whose achivement is difficult with conventional 2D
      ultrasound. Surface rendering provides excellent spatial vision and enables
      parents to understand the severity of the malformation thus helping with their
      decisions.

PMID- 21966848
TI  - [Cervical meningocele with filiform connection. Case report].
AB  - The meningocele is the least common form of spina bifida cystica and represents
      less than 10% of cases of this disorder. A case of a female patient aged 26 with
      a history of two pregnancies and two previous cesarean sections, present
      pregnancy unplanned, uncontrolled during the first trimester prenatal and without
      supplementation with folic acid. Family history of consanguinity with her husband
      (second cousins) and psychomotor reassessed in four maternal cousins. The first
      follow-up visit the patient was at 34 weeks of pregnancy. The ultrasonographic
      findings were: cervical meningocele posterior filiform connection between the
      first and second cervical vertebrae, lateral ventriculomegaly and third and
      fourth ventricles and hydrocephalus secondary. Cesarean section was performed at
      37 weeks gestation and was a newborn male 3.000 g, 52 cm, head circumference of
      36 cm, Apgar 8/9, Capurro 37 weeks of gestation. In the posterior cervical region
      tumor was located a soft 5 x 5 cm with intact skin, adhered to deep planes.
      Movement of all four extremities without neurological involvement. He referred to
      the department of neurosurgery for shunt placement and subsequently performed
      surgical excision of the meningocele.

PMID- 21966849
TI  - [Sirenomelia apus. Case report].
AB  - We report a case of Sirenomelia. The mother began prenatal care in the second
      trimester. Transabdominal ultrasound was determined anhydramnios, cardiac
      abnormalities and lumbosacral spine. We obtained a single fetus of 21 weeks'
      gestation with fused lower extremities from the hip to finish in a stump without
      the presence of feet. Heart with transposition of the great vessels, among other
      birth defects. It was classified as symelia, Apodi apus, monopodio sirenoide,
      siren ectropodia, type VI. It is important to diagnose early, because it is a
      serious and deadly disorder.

PMID- 21966850
TI  - [Spontaneous heterotopic pregnancy and fetal survival].
AB  - The spontaneous heterotopic pregnancy is an unusual event. Generally the
      extrauterine product lost and the intrauterine present complications in different
      grade. The most common is the rupture and can be associated with hemodynamic
      unstable with risk for patient's life. The intrauterine pregnancy can be
      continuing to the end. We report the case of patient with spontaneous heterotopic
      pregnancy; the diagnosis was in the first trimester, with two products
      (intrauterine and in right fimbrius). The salpingectomy is doing with the
      extrauterine pregnancy and the patient has not complications trans or
      postoperative time and without complications for the intrauterine pregnancy, she
      continues with stricter control until to obtain a life product.

PMID- 21966851
TI  - [Considerations on 113 cases of application of mid-forceps.1956].

PMID- 21966852
TI  - [Prevalence of urinary incontinence in pregnant women with prenatal care at the
      National Institute of Perinatology Isidro Espinosa de los Reyes].
AB  - BACKGROUND: Urinary incontinence during pregnancy is relatively frequent and is
      seen in some cases as a normal event. Several authors estimate a prevalence of
      urinary incontinence during pregnancy of 58.1%. OBJECTIVE: To determine the
      prevalence of urinary incontinence in women at the National Institute of
      Perinatology Isidro Espinosa de los Reyes from March to May 2008. We also
      assessed the type, severity and frequency of involuntary loss of urine. PATIENTS
      AND METHODS: longitudinal study to determine the prevalence of urinary
      incontinence before and during pregnancy, by quarter, type, frequency and
      severity. RESULTS: The prevalence of urinary incontinence during pregnancy was
      58.2% and before pregnancy was 34.7%. The odds ratio for the association of
      multiparity and incontinence before pregnancy was 1.7 (95% CI 1.2-2.5) and 2.0
      (95% CI 1.4-2.9) to manifest during pregnancy. Patients under 26 years have an
      odds ratio for urinary incontinence of 0.67 (95% CI 0.4-0.9). CONCLUSION: The
      prevalence of urinary incontinence increases during pregnancy, multiparity is a
      risk factor for urinary incontinence and age under 26 is a protective factor.

PMID- 21966853
TI  - [Hormonal contraception as a risk factor for developing cervical cancer:
      biological, epidemiological and immunological evidence].
AB  - BACKGROUND: Cervical cancer has been extensively studied, as well as the various
      risk factors for that cancer. One such factor is the prolonged use of hormonal
      contraceptives. OBJECTIVE: To report the biological, immunological and
      epidemiological findings arising from the use of oral contraceptives and their
      relation to cervical cancer. MATERIAL AND METHODS: Retrospective study based on
      information published in national and international literature. CONCLUSIONS:
      Controversy persists between the epidemiological data and experimental biological
      association between hormonal contraceptives and cancer induced by HPV. It is
      important to consider the biological findings because in Mexico the use of
      hormonal contraceptives is very broad and the number of cases of cervical cancer
      and only extensive epidemiological studies will clarify this controversy.

PMID- 21966854
TI  - [Postpartum urinary and fecal incontinence in gemelar pregnancy according to
      route and mode of delivery].
AB  - BACKGROUND: The incidence of multiple pregnancies increased in the last two
      decades. Several studies seeking the incidence of pelvic floor pathology,
      particularly urinary incontinence and its risk factors, conclude that a previous
      cesarean and vaginal delivery even more, carry an increased risk for developing
      urinary and fecal incontinence, compared with patients nulligravida. OBJECTIVE:
      To determine the different risk factors for urinary incontinence after a twin
      pregnancy. PATIENTS AND METHODS: 331 women from 20 to 50 years of age without
      symptoms prior to pregnancy were interviewed, attending antenatal care of twin
      pregnancy in the Hospital La Paz, Madrid. The interview included the ICIQ-SF
      (International Consultation on Incontinence Questionnaire-Short Form). We
      recorded maternal age, gestational age, parity, episiotomy, weights of both
      newborns, the need for urinary protectors and fecal or gas incontinence. RESULTS:
      The prevalence of urinary incontinence postpartum according ICIQ-SF >0 was 23%;
      20.4% in the caesarean group, 25.3% in the eutocic delivery group and 35.5% in
      the instrumental delivery group (p = 0.033). The prevalence of moderate to severe
      incontinence (ICIQ-SF >6) was 14.8%; 12.3% in caesarean group, 14.5% in the
      eutocic delivery group and 32.3% in the instrumental delivery group (p = 0.005).
      The prevalence of fecal incontinence was 3.4%; 4.8% in eutocic delivery group,
      1.9% in the caesarean group and 9.7% in the instrumental delivery group (p =
      0.058). CONCLUSIONS: The risk of urinary incontinence after a twin pregnancy was
      higher among patients who had an instrumental delivery when compared with
      patients with eutocic delivery or cesarean section. The total fetal weight and
      maternal age did not appear as risk factors in our study. Any woman who had an
      instrumental delivery for twins should be followed up by a pelvic floor
      specialist.

PMID- 21966855
TI  - [Teaching of total laparoscopic hysterectomy in a gynecological laparoscopy
      university diploma course].
AB  - BACKGROUND: Total laparoscopic hysterectomy is a procedure that requires proper
      training so that implementation is safe and effective. OBJECTIVE: To describe the
      clinical outcomes of the teaching of total laparoscopic hysterectomy in a
      university program. PATIENTS AND METHODS: for a period of two years (2009-2010),
      18 doctors enrolled in the diploma program in gynecological laparoscopy conducted
      at the Hospital Civil de Culiacan, Sinaloa, made 82 total laparoscopic
      hysterectomy. Were analyzed: age and gender of the participating physicians,
      exercise time of gynecology, general characteristics of the patients,
      indications, route of access to the pneumoperitoneum, duration of procedure,
      intraoperative and postoperative complications, size and weight of the uterus,
      closing time of the dome by laparoscopy and laparotomy conversion rate. RESULTS:
      The median age of physicians was 34 years (range 28 to 50 years), 69.2% were
      male, seven years on average for the exercise of gynecology (range 1 to 20
      years). The mean procedure time was 121.5 minutes (95% CI 110.5-132.4), the mean
      uterine size was 12.1 cm (95% CI 11.3-12.8) and uterine weight of 229.6 g (95%:
      182.5-276.7). The average intraoperative bleeding was 133.9 mL (95% CI 112.9
      154.8), hospital stay was 24.8 hours (95% CI 23.1-26.4). Major complications
      occurred in 1.2% of patients (95% CI 0.6-5.8). Minor complications were
      demonstrated in 7.3% of procedures (95% CI 3.01-14.5). The frequency of
      conversion to abdominal hysterectomy was 1.2% (95% CI 0.6-5.8). CONCLUSION: Total
      laparoscopic hysterectomy was performed safely and efficiently by training
      students in university teaching program in gynecologic laparoscopy.

PMID- 21966856
TI  - [Letrozole vs. tamoxifen as neoadjuvant therapy for postmenopausal patients with
      hormone-dependent locally-advanced breast cancer].
AB  - BACKGROUND: Previous studies demonstrated that Letrozole (aromatase inhibitor)
      and tamoxifen (selective modulator of estrogen receptors) are effective in the
      treatment of postmenopausal women with locally advanced tumors, stage III and
      hormone dependent. OBJECTIVE: To present display the complete clinical answer
      incidence and the complete pathological answer with the use of induction
      hormonotherapy. METHODS: Put-analysis in 40 patients with breast cancer, to
      chanalicular infiltrated, eligible were treated in a prospective study, to double
      blind person, using per os: letrozol, 2.5 mg; tamoxifen, 20 mg, known widely like
      selective modulator of estrogen receivers; oral route, during 36 consecutive
      months. Reports at the beginning were taken, subsequent to 3, 6 and 12 months to
      evaluate the frequency of complete respond. The patients, who did not show answer
      neoadjuvant therapy, were put under treatment with radiotherapy. The patients who
      showed good partial pathological respond, or clinical partial respond, went
      candidates to radical mastectomy. According to the protocol of the study, the
      patients subsequent to surgery who showed partial pathological respond or
      complete pathological respond, continued adjuvant handling adyuvant therapy by 2
      years consecutive or until the presence of progression of the disease. It was
      used like statistical method Chi2, with p of Table cloth to evaluate the
      differences. RESULTS: During a period of 3 years, january of the 2003 to january
      of the 2005, 2 groups of patients, 40 studied altogether; the age average was of
      65,5 years, with a rank of 55 to 75 years with breast cancer, stages: IIA to
      IIIB. Without complete respond 25% of the group with tamoxifen; 20% with letrozol
      Those patients happened to radiotherapy. The collateral effects of the use of
      hormonotherapy with letrozol appeared in a 55% and with the use of tamoxifen in a
      60% of the patients with breast cancer (p = 0.5). They did not respond to
      neoadyuvant therapy (hormonal receptors < to 30%): with letrozol 19% of them and
      25% with tamoxifen; reason why they received treatment with radiotherapy. All
      patients candidates to surgery, were benefitted with the mastectomy handling.
      CONCLUSIONS: Results although preliminary, suggest that neoadyuvant treatment
      with hormone-therapy in postmenopausal patients with breast cancer, have good
      prognosis. Induction therapy, were better tolerated, with greater effectiveness
      and improved the clinical and objective respond in women with breast cancer in
      the postmenopausal. Work serves as tool to determine the indication to us of
      induction hormonotherapy; and identify to those patients with breast cancer,
      locally advanced in post menopause with better prognosis to be rescued with
      radical mastectomy. Study needs more background and show the impact of letrozol,
      as hormonotherapy used in neoadjuvancy, to confirm if relieves period without
      disease or survives, before mastectomy. In a near future, it shall important to
      investigate if is useful the radical mastectomy in those postmenopausal patients
      with complete objective respond, after the use of an aromatase inhibitor.

PMID- 21966857
TI  - [Epidemiological profile of ovarian cancer].
AB  - BACKGROUND: In Mexico, ovarian cancer represents 5.3% of cancer diagnoses in all
      age groups and 21% of gynecologic cancers. The states with the highest incidence
      of this disease Nuevo Leon, Mexico State and Federal District. OBJECTIVE: To
      determine the epidemiological profile of ovarian cancer. PATIENTS AND METHODS: A
      retrospective cross-sectional study that included all patients with complete
      records, diagnosed with ovarian cancer treated at the Oncology department UMAE
      Monterrey No. 23, January 2009 to 31 December 2009. RESULTS: We identified 40
      patients with ovarian cancer. The average age of menarche was 12.7 years, 40%
      were of reproductive age, 25% were nulliparous, 15% had a pregnancy and 37.5% had
      two pregnancies. Of the total patients, 17% had a history of breast cancer, 40%
      used a contraceptive method, 37% used oral contraceptives. The tumor marker CA
      125 was found in 40% of patients, 63.1% had ultrasound markers for cancer. The
      most frequent clinical stage 1A in which they found 32% of cases. Papillary
      serous adenocarcinoma was diagnosed in 25% of patients, endometroid
      adenocarcinoma and mucinous tumor of low malignant potential was diagnosed
      borderline at 20%, poorly differentiated adenocarcinoma in 18% tumor granulosa
      cells in 7% and papillary adenocarcinoma ring cell adenocarcinoma in 5%. In
      total, 43% of patients received chemotherapy. CONCLUSION: The majority of cases
      tenia50 years or more. The background was the most frequent hereditary breast
      cancer. There were no deaths during the study.

PMID- 21966858
TI  - [Effect of betamethasone in blood glucose levels in pregnant diabetic women at
      risk of preterm birth].
AB  - BACKGROUND: The bethametasone (BTM) induced hyperglycemia is not adequately known
      and managed in diabetic pregnant women. OBJECTIVE: To compare the betamethasone
      induced hyperglycemia in pregnant women either healthy or with gestational or
      type 2 diabetes mellitus (diabetes mellitus). MATERIAL AND METHODS: Forty
      volunteer pregnant women at risk of premature rupture of membranes who received
      betamethasone (12 mg i.m. every 24 hours, 2 doses) were divided in four groups
      (10 women each): G1, healthy; G2, Diet treated diabetes mellitus; G3, Diet plus
      insulin treated diabetes mellitus; G4, type 2 diabetes mellitus treated with diet
      (n=6) or diet and insulin (n=4). Pre (p) and 2h-postprandial (pp) capillary blood
      glucose was measured throughout the day during 5 days of hospitalization.
      Student't test for independent and dependent samples was used. RESULTS: G1 had no
      significant changes in p or pp glucose. In G2 four women required de novo insulin
      administration while insulin dose was increased 39 to 112% and 26 to 64% in all
      women in G3 and G4, respectively to maintain p and pp glucose levels <95 mg/dL
      and < 120 mg/dL, respectively. The greatest changes occurred between days 2 to 4
      after betamethasone. CONCLUSION: Betamethasone-induced hyperglycemia was greater
      in insulin treated women with gestational or type 2 diabetes and should not be
      administrated on an out-patient basis.

PMID- 21966860
TI  - [Critical thinking about modern helper methods in the diagnosis in gynecology.
      1956].

PMID- 21966859
TI  - [Fibromyalgia and menopause. Association or coincidence?].
AB  - Fibromyalgia constitutes today, in the western world, an important problem of
      health that affects fundamentally in women from 45 years. The studies on the
      influence of the hormones on the symptomatology of the patients with fibromyalgia
      have not managed to establish a link of causal union between the hormonal
      climacteric decline and the development of the painful syndrome. Nevertheless,
      there are studies that relate the pain, the anxiety and the depression to the
      level of sexual steroids. It is our aim to check these associations. We will have
      to expect to the development of the intracrinology and, possibly, to know more
      the relationship between sexual steroids and neurotransmitters to be able to know
      the exact relation between fibromyalgia and menopause.

PMID- 21966861
TI  - [3 breast nipples - polythelia. Why the kidneys should be checked in this case].

PMID- 21966862
TI  - [Positive anti-Borrelia antibody test: still not confirmation of borreliosis].

PMID- 21966863
TI  - [Autopsy: the last diagnosis--a case for the police?].

PMID- 21966864
TI  - [Naturopathy consultation. Acne].

PMID- 21966865
TI  - [Your are the expert for anamnesis and psychosomatic primary care. Keep your
      patients from diagnostic Odyssey].

PMID- 21966866
TI  - [Evidence-based therapeutic algorithms in the treatment of depression, dementia
      and psychosis in Parkinson's disease].

PMID- 21966867
TI  - [The patient with bipolar disorder in primary care--manic or just "in a good
      mood"?].

PMID- 21966868
TI  - [Depressive disorders in children and adolescents].

PMID- 21966869
TI  - [How to detect neuropathic pain].

PMID- 21966870
TI  - [Update migraine therapy].

PMID- 21966871
TI  - [BPSD: behavioural and psychological symptoms of dementia].

PMID- 21966872
TI  - [Epilepsy: recommendations for daily activities].

PMID- 21966873
TI  - [Multiple sclerosis: can therapy delay ongoing disability?].

PMID- 21966874
TI  - [Smoking cessation--assistance for the general practitioner].

PMID- 21966875
TI  - [Alcohol withdrawal].

PMID- 21966876
TI  - [Juvenile schizophrenia: diagnosis, therapy, prognosis].

PMID- 21966877
TI  - [Because depression also hurts: duloxetine can help patients return to vitality].

PMID- 21966878
TI  - [Interview with Dr. Heike-Ariane Washeim, Zirndorf, and Dr. Heiner Buschmann,
      Ubach-Palenberg (interview by Abdol A. Ameri)].

PMID- 21966879
TI  - Osteogenic differentiation of human mesenchymal stem cells cultured with
      dexamethasone, vitamin D3, basic fibroblast growth factor, and bone morphogenetic
      protein-2.
AB  - PURPOSE: Human mesenchymal stem cells (hMSCs) are pursued for cell-based
      therapies of bone defects. Successful use of hMSCs will require them to be
      osteogenically differentiated before transplantation. This study was intended to
      determine the optimal combination(s) of supplements needed for inducing
      osteogenesis in hMSCs. METHODS: The hMSCs were cultured with combinations of beta
      glycerophosphate, dexamethasone (Dex), vitamin D3 (Vit-D3), basic fibroblast
      growth factor (bFGF), and bone morphogenetic protein-2 (BMP-2) to assess cell
      growth and osteogenesis. Osteogenic responses of the supplements were evaluated
      by alkaline phosphatase (ALP) activity, mineralization, and gene expression of
      ALP, Runx2, bone sialoprotein, and osteonectin. Adipogenesis was characterized
      based on Oil Red O staining, gene expression of peroxisome proliferator-activated
      receptor gamma2, and adipocyte protein-2. RESULTS: Dex was found to be essential
      for mineralization of hMSCs. Cultures treated with Dex (100 nM), Vit-D3 (10/50
      nM), and BMP-2 (500 ng/mL) demonstrated maximal calcification and up-regulation
      of ALP and bone sialoprotein expression. However, adipogenesis was up-regulated
      in parallel with osteogenesis in these cultures, as evident by the presence of
      lipid droplets and significant up-regulation of peroxisome proliferator-activated
      receptor gamma2 and adipocyte protein-2 expression. An optimal condition was
      obtained at Dex (10 nM) and BMP-2 (500 ng/mL) for mineralization without
      increasing adipogenesis-related markers. The bFGF mitigated osteogenesis and
      enhanced adipogenesis. Vit-D3 appears essential for calcification only in the
      presence of bFGF. CONCLUSION: Treatment of hMSCs with appropriate supplements at
      optimal doses results in robust osteogenic differentiation with minimal
      adipogenesis. These findings could be used in the cultivation of hMSCs for cell
      based strategies for bone regeneration.

PMID- 21966880
TI  - Novel methoxylated polybrominated diphenoxybenzene congeners and possible sources
      in herring gull eggs from the Laurentian Great Lakes of North America.
AB  - An increasing number of brominated flame retardants and other brominated
      substances are being reported in herring gull eggs from the Laurentian Great
      Lakes basin. Yet, in extracts from gulls' eggs, numerous bromide anion response
      peaks in electron capture negative ion (ECNI) mass chromatograms remain
      unidentified. Using archived herring gull egg homogenates, we characterize the
      structures of three major and three minor, new and unique brominated substances.
      After extensive cleanup and separation to isolate these substances from the
      extracts, high-quality ECNI and electron impact (EI) mass spectra revealed
      fragmentation patterns consistent with congeners of methoxylated polybrominated
      diphenoxybenzene (MeO-PBDPB), where four congeners contained five bromines and
      the other two contain four and six bromines, respectively. Optimized,
      semiquantitative analysis revealed sum concentrations of the MeO-PBDBP congeners
      ranged from <0.2 to 36.8 ng/g ww in pooled egg homogenates (collected in 2009)
      from fourteen herring gull colony sites across the Great Lakes, with the highest
      concentration being for Channel-Shelter Island in Saginaw Bay (Lake Huron). To
      our knowledge, there are no published reports on the environmental presence and
      sources of MeO-PBDPBs. We hypothesize that these MeO-PBDPBs are degradation
      products of the polybrominated diphenoxybenzenes, for example,
      tetradecabromodiphenoxybenzene (currently marketed as SAYTEX 120) or polybromo
      3P2E. MeO-PBDPBs in Great Lakes herring gull eggs indicates their bioaccumulation
      potential, and raises concerns about their origin, environmental behavior and
      influences on wildlife and environmental health.

PMID- 21966881
TI  - Propionyl-L-carnitine, L-arginine and niacin in sexual medicine: a nutraceutical
      approach to erectile dysfunction.
AB  - The application of nutraceuticals in the field of male sexual function -in
      particular for erectile dysfunction (ED)--remains relatively underexplored. In a
      group of 54 unselected men (35-75 years), consecutively presenting to our ED
      clinic and naive to other ED treatments, we carried out a single-blind, one-arm
      study to evaluate the effects of a 3-month supplementation with propionyl-L
      carnitine, L-arginine and niacin on their sexual performance. All patients had
      the short-international index of erectile function (IIEF) questionnaire, global
      assessment questions (GAQs) and routine laboratory testing, at baseline and 3
      months afterward. 51 (92%) patients of 54 completed the entire study period.
      After 3 months of treatment, a small, but statistically significant improvement
      in total and single items of the IIEF was found (Delta = 5.7 +/- 4.1 P < 0.01).
      Analyses on GAQs revealed that treatment improved erections in 40% of cases, with
      a partial response occurring in up to 77% of subjects enrolled. These preliminary
      findings indicate that the favourable cardiovascular effects of nutraceuticals
      might also reflect on male sexual function with possible implication in the
      treatment and prevention of ED. This study documents a considerable patient's
      interest toward nutritional supplementation--as first-line or adjunctive
      treatment to PDE5 inhibitors--that goes beyond the measurable increment in penile
      rigidity.

PMID- 21966885
TI  - Reducing lesion aberration by dual-frequency focused ultrasound ablations.
AB  - Discrepancies between hyperecho-predicted necrosed volume in ultrasound (US)
      images and the actual size of a thermal lesion might cause incomplete ablation or
      damage normal structures during high intensity focused US (HIFU) ablations. A
      novel dual-frequency sonication procedure is proposed to reduce this discrepancy.
      HIFU transducers of either 1 or 3.5 MHz were applied to transparent tissue
      mimicking phantoms and ex vivo bovine liver samples. A diagnostic probe and a
      charge-coupled device (CCD) camera were used to record lesion formation in real
      time, allowing for comparison of the sizes of the hyperechoes in US images and
      the protein denaturing area on optical images. Bovine liver specimens were
      segmented to reveal the lesion's terminal sizes. Differences between actual
      lesion volume and hyperechoes in US images were demonstrated to be dependent on
      acoustic frequency and intensity. At a low frequency (1 MHz), the hyperechoes
      appeared to be larger than the actual volume, but the difference decreased with
      the duration of ablation. In contrast, at a high frequency (3.5 MHz), the
      hyperechoes were smaller for ablations lasting longer than 10 s. Moreover, given
      certain low-intensity conditions, lesions were formed without detectable
      hyperechoes (3.5 MHz), or hyperechoes appeared before a visible lesion was formed
      (1 MHz). Dual frequency sonications (low frequency followed by high frequency)
      produce more stable and larger lesions, and with less position shift, which might
      be useful for designing future ablation strategies.

PMID- 21966886
TI  - Caspase pathway of elaidic acid (9t-C18:1)-induced apoptosis in human umbilical
      vein endothelial cells.
AB  - Although TFAs (trans fatty acids) do have effects on many endothelial functions,
      systemic inflammation and immune disorders, only limited experimental evidence is
      available that TFAs participate in the pathogenesis of endothelial cell
      apoptosis. HUVEC (human umbilical vein endothelial cells) were grown in medium
      with elaidic acid (9t-C18:1) at 50, 100, 200 and 400 MUmol/l for 24 h. Apoptosis
      was measured by flow cytometry, and caspase 3, 8 and 9 activities by colorimetric
      assay and their mRNA expression by qRT-PCR (quantitative real-time PCR). Results
      showed that 9t-C18:1 induced apoptosis of HUVEC in a dose-dependent manner. The
      activities and mRNA expression of caspases 8, 9 and 3 were significantly
      increased compared with that of the control. Z-IETD-FMK and Z-LEHD-FMK inhibited
      the activation of caspase 3 and apoptosis induced by 9t-C18:1. Also Z-IETD-FMK
      inhibited the activation of caspase 9. mRNA expressions of Bid and Smac (second
      mitochondria-derived activator of caspase)/DIABLO [direct IAP (inhibitor of
      apoptosis)-binding protein with low pI] were also significantly elevated. We
      conclude that 9t-C18:1 induces apoptosis of HUVEC through activating caspases 8,
      9 and 3. The death receptor pathway and the mitochondrial pathway both
      participated in the apoptosis course induced by 9t-C18:1.

PMID- 21966887
TI  - Time since stroke influences the impact of hemianopia and spatial neglect on
      visual-spatial tasks.
AB  - OBJECTIVE: Spatial neglect results in an ipsilesional misorientation of attention
      in visual-spatial tasks. Hemianopia impairs visual perception but its influence
      on visual-spatial tasks is subject to debate. Here, we investigated the influence
      of the time since stroke on the respective impacts of hemianopia and spatial
      neglect. METHOD: A total of 29 patients with a right hemisphere stroke were
      included in the study. Nine had severe neglect and hemianopia, six had severe
      neglect only, four showed hemianopia with little or no neglect after infarction
      of the posterior cerebral artery, and 10 had neither neglect nor hemianopia. We
      investigated the spatial bias in the subjective straight ahead (SSA) test and in
      clinical tests (bell cancellation, line bisection, and scene copy). Each task was
      administered twice (at S1 and S2: 41.4 and 67.2 days [on average] after the
      stroke, respectively). RESULTS: At S1, spatial neglect and hemianopia had an
      additive influence on SSA test performance (rightward translation). Similar
      rightward biases were observed in the clinical tests. At S2, the influence of
      hemianopia had disappeared, whereas that of neglect was still present.
      Furthermore, loss of bias in the SSA test correlated with the improvements seen
      in most of the clinical tests. CONCLUSIONS: In patients with recent stroke,
      hemianopia aggravates the visual-spatial bias when neglect is present or may lead
      to visual-neglect-like behavior when classically defined neglect is absent.
      However, the influence of hemianopia disappears relatively quickly over time, due
      to compensation.

PMID- 21966888
TI  - In vitro rumen fermentation and methane production are influenced by active
      components of essential oils combined with fumarate.
AB  - Two trials were conducted to identify the optimal levels of essential oil active
      components (EOAC) and their combination with fumarate on in vitro rumen
      fermentation. In trial 1, eugenol, carvacrol, citral and cinnamaldehyde were
      mixed at ratios of 1:2:3:4, 2:1:4:3, 3:4:1:2, 4:3:2:1 and 1:1:1:1 to make up five
      combinations (EOAC1, EOAC2, EOAC3, EOAC4 and EOAC5 respectively). The mixtures
      were supplied at levels of 0, 50, 200 or 500 mg/l to identify the optimal
      combination for methane reduction. Methane production and ammonia nitrogen were
      decreased by adding EOAC, irrespective of component compounds, but the production
      of gas and total volatile fatty acids (VFA) were also decreased. Hydrogen balance
      analysis indicated that the ratio of hydrogen consumed via methane to hydrogen
      consumed via VFA was lowest at 200 mg/l of EOAC5 treatment, from which the
      proportional change in methane was more than the change in VFA, with 31.5% of
      methane reduction and 12.9% of VFA reduction. In trial 2, 200 mg/l of EOAC5 was
      added with 0, 5, 10 and 15 mm monosodium fumarate to see whether fumarate had a
      further effect on rumen fermentation. The addition of fumarate had no influence
      on gas production, but it further decreased methane and increased the total VFA
      in comparison with EOAC added solely, with the greatest decrease occurring in
      methane (78.1%) from 10 mm of fumarate. Quantification of the microbial
      populations in rumen fluids by RT-PCR showed that methanogen, protozoa, fungi,
      Fibrobacter succinogenes and Ruminococcus flavefaciens populations were
      significantly decreased by EOAC5, but were not influenced by fumarate. In
      summary, the addition of EOAC had consistent effects on rumen fermentation
      parameters, but high levels of EOAC would induce the inhibition of rumen
      fermentation. Adding fumarate can enhance the methane-inhibiting effect of EOAC,
      and the decrease was higher than that calculated stoichiometrically.

PMID- 21966889
TI  - Discovery, synthesis, and structure-activity relationship development of a series
      of N-4-(2,5-dioxopyrrolidin-1-yl)phenylpicolinamides (VU0400195, ML182):
      characterization of a novel positive allosteric modulator of the metabotropic
      glutamate receptor 4 (mGlu(4)) with oral efficacy in an antiparkinsonian animal
      model.
AB  - There is an increasing amount of literature data showing the positive effects on
      preclinical antiparkinsonian rodent models with selective positive allosteric
      modulators of metabotropic glutamate receptor 4 (mGlu(4)). However, most of the
      data generated utilize compounds that have not been optimized for druglike
      properties, and as a consequence, they exhibit poor pharmacokinetic properties
      and thus do not cross the blood-brain barrier. Herein, we report on a series of N
      4-(2,5-dioxopyrrolidin-1-yl)phenylpicolinamides with improved PK properties with
      excellent potency and selectivity as well as improved brain exposure in rodents.
      Finally, ML182 was shown to be orally active in the haloperidol induced catalepsy
      model, a well-established antiparkinsonian model.

PMID- 21966890
TI  - Use of the Montreal global definition as an assessment of quality of life in
      reflux disease.
AB  - According to the Montreal Consensus Group's classification, gastroesophageal
      reflux disease develops when the reflux of stomach contents causes troublesome
      symptoms and/or complications such as esophagitis. The characteristic
      gastroesophageal reflux disease symptoms included in this statement are
      retrosternal burning and regurgitation. Troublesome is meant to imply that these
      symptoms impact on the well-being of affected individuals; in essence, quality of
      life (QOL). Whether heartburn and regurgitation symptoms would be characterized
      as more troublesome in those with confirmed pathologic acid reflux was
      determined. A second purpose was to assess how well troublesome scores correlated
      with the results of a validated, disease-specific QOL instrument. Subjects who
      underwent esophagogastroduodenoscopy (EGD) with 48-hour wireless esophageal pH
      testing off proton pump inhibitor therapy were interviewed. Esophagitis on EGD or
      pH < 4.0 for >=4.5% of time over the 2-day period was considered positive for
      acid reflux. Assessment of how troublesome their symptoms of heartburn and
      regurgitation were made using separate 0-100 visual analog scales (VAS). Subjects
      were then asked to complete the Quality of Life in Reflux and Dyspepsia (QOLRAD)
      25-item questionnaire. Sixty-seven patients (21 males, 46 females) with mean age
      47.8 +/- 15.6 years were identified. Forty (59.7%) had an EGD or pH study
      positive for acid reflux. Overall 35/40 (87.5%) complained of either heartburn or
      regurgitation. There was no difference (P= 0.80) in heartburn VAS troublesome
      ratings for those with (54.0 +/- 43.9) and without (56.7 +/- 37.6) confirmed acid
      reflux. The same was true for regurgitation VAS troublesome ratings (P= 0.62).
      Likewise, mean QOLRAD scores did not differ between those with and without
      confirmed acid reflux by pH or EGD (4.5 +/- 1.7 vs. 4.3 +/- 1.7; P= 0.61). There
      was a moderately strong inverse correlation between patient self-rated VAS
      troublesome scores for both heartburn and regurgitation with each dimension
      (emotional distress, sleep disturbance, eating problems, physical/social
      functioning, and vitality) of the QOLRAD (P < 0.05 for all comparisons). In
      regression analysis, both heartburn and regurgitation troublesome ratings were
      associated with the overall QOLRAD score independent of pH data, frequency of
      reflux episodes, age, and gender. Use of the term troublesome in the Montreal
      Consensus Group classification is supported by our findings. It correlates well
      with the results of a validated disease-specific QOL instrument. Use of heartburn
      and regurgitation VAS may serve as accurate measures of the burden of reflux
      disease on patients. It is likely that these scales will not have sufficient
      discriminate value to identify individuals with pathologic acid reflux from those
      with negative studies.

PMID- 21966891
TI  - 25-Hydroxyvitamin D levels in African-American and Caucasian/Hispanic subjects
      with cutaneous lupus erythematosus.
AB  - BACKGROUND: Because exposure to ultraviolet radiation accounts for a significant
      portion of endogenous vitamin D production, subjects with cutaneous lupus (CLE)
      who practise sun-protective measures are at risk for vitamin D insufficiency.
      Previous studies have shown light-skinned subjects with CLE to have lower serum
      25-hydroxy (25-OH) vitamin D levels than normal controls. OBJECTIVES: To assess
      the status of vitamin D insufficiency in dark-skinned individuals with CLE.
      METHODS: We performed a cross-sectional study comparing serum 25-OH vitamin D
      levels in 25 African-American (AA) subjects with CLE and 26 normal AA subjects
      matched by age, sex and season in Dallas, Texas. A questionnaire on demographics,
      medical history and lifestyle habits was administered to determine factors
      potentially affecting vitamin D levels. Findings were contrasted to a similar
      comparison in 26 Caucasian and Hispanic (C/H) subjects with CLE and 24 normal C/H
      subjects matched by age, sex and season. RESULTS: We found similar mean+/-SD 25
      OH vitamin D levels in AA subjects with CLE (52.0+/-18.5nmolL(-1) ) and normal AA
      subjects (54.8+/-21.2 nmolL(-1) ) (P=0.62). Almost half of AA subjects in both
      groups were vitamin D insufficient. A larger difference in 25-OH vitamin D levels
      was found between C/H subjects with CLE (59.4+/-21.0nmolL(-1) ) and normal C/H
      subjects (70.5+/-27.4nmolL(-1) ) (P=0.12). Two-way anova demonstrated that skin
      colour (AA vs. C/H) had a significant effect on 25-OH vitamin D levels (P=0.008),
      although CLE status (CLE vs. normal) did not (P=0.13). CONCLUSIONS: Providers are
      encouraged to address vitamin D insufficiency concerns in all dark-skinned
      individuals. Future studies should stratify subjects by skin colour in
      determining differences between subjects with CLE and normal controls.

PMID- 21966893
TI  - Cross-validated stepwise regression for identification of novel non-nucleoside
      reverse transcriptase inhibitor resistance associated mutations.
AB  - BACKGROUND: Linear regression models are used to quantitatively predict drug
      resistance, the phenotype, from the HIV-1 viral genotype. As new antiretroviral
      drugs become available, new resistance pathways emerge and the number of
      resistance associated mutations continues to increase. To accurately identify
      which drug options are left, the main goal of the modeling has been to maximize
      predictivity and not interpretability. However, we originally selected linear
      regression as the preferred method for its transparency as opposed to other
      techniques such as neural networks. Here, we apply a method to lower the
      complexity of these phenotype prediction models using a 3-fold cross-validated
      selection of mutations. RESULTS: Compared to standard stepwise regression we were
      able to reduce the number of mutations in the reverse transcriptase (RT)
      inhibitor models as well as the number of interaction terms accounting for
      synergistic and antagonistic effects. This reduction in complexity was most
      significant for the non-nucleoside reverse transcriptase inhibitor (NNRTI)
      models, while maintaining prediction accuracy and retaining virtually all known
      resistance associated mutations as first order terms in the models. Furthermore,
      for etravirine (ETR) a better performance was seen on two years of unseen data.
      By analyzing the phenotype prediction models we identified a list of forty novel
      NNRTI mutations, putatively associated with resistance. The resistance
      association of novel variants at known NNRTI resistance positions: 100, 101, 181,
      190, 221 and of mutations at positions not previously linked with NNRTI
      resistance: 102, 139, 219, 241, 376 and 382 was confirmed by phenotyping site
      directed mutants. CONCLUSIONS: We successfully identified and validated novel
      NNRTI resistance associated mutations by developing parsimonious resistance
      prediction models in which repeated cross-validation within the stepwise
      regression was applied. Our model selection technique is computationally feasible
      for large data sets and provides an approach to the continued identification of
      resistance-causing mutations.

PMID- 21966894
TI  - Proteomic profiling of human respiratory epithelia by iTRAQ reveals biomarkers of
      exposure and harm by tobacco smoke components.
AB  - Historically, it has been challenging to go beyond epidemiology to investigate
      the pathogenic changes caused by tobacco smoking. The EpiAirway-100 (MatTek
      Corp., Ashland, MA) was employed to investigate the effects of cigarette smoke
      components. Exposure at the air-liquid-interface represented particle and vapour
      phase components of cigarette smoke. A proteomic study utilising iTRAQ labelling
      compared expression profiles. The correlative histopathology revealed focal
      regions of hyperplasia, hypertrophy, cytolysis and necrosis. We identified 466
      proteins, 250 with a parameter of two or more peptides. Four of these proteins
      are potential markers of lung injury and three are related to mechanistic
      pathways of disease.

PMID- 21966895
TI  - Utility of the posterior to anterior mitral valve leaflets length ratio in
      prediction of outcome of percutaneous balloon mitral valvuloplasty.
AB  - BACKGROUND: Scoring of mitral stenosis (MS) severity is very important for
      selection of patients for balloon mitral valvuloplasty (BMV). OBJECTIVE: We
      propose a novel yet simple, independent parameter of MS severity based on the
      posterior mitral valve leaflet to anterior mitral valve leaflet length ratio
      (PMVL/AMVL length ratio). It could be a useful predictor to outcome of BMV.
      SUBJECTS AND METHODS: A total of 106 patients (mean age 29.1 +/- 8.6 years) had
      MS with mitral valve score of eight or less. The length of anterior mitral valve
      leaflet and posterior mitral valve leaflet were measured. Patients were
      classified into group with ratio >=1/2 and group of ratio <1/2. Eighty-five
      healthy control subjects were studied. RESULTS: Patients with PMVL/AMVL ratio
      >=1/2 post-BMV had lower transmitral gradients (4.5 +/- 3.1 mmHg vs. 9.7 +/- 2.1
      mmHg, P < 0.002) and greater mitral valve area (MVA) (2.09 +/- 0.3 cm(2) vs. 1.5
      +/- 0.2 cm(2) , P < 0.001), lower pulmonary artery systolic pressure (PASP) (23.8
      +/- 14.3 mmHg vs. 34.2 +/- 12.5 mmHg, P < 0.001), left atrial pressure (10.2 +/-
      6.7 mmHg vs. 18.9 +/- 6.4 mmHg, P < 0.001), and lower incidence of de novo or
      worsening of mild mitral regurgitation (MR; 1.64% vs. 8.9%, 0% vs. 6.6%, P <
      0.001). PMVL/AMVL length ratio was positively correlated with post-BMV MVA (r =
      0.69, P < 0.002), PASP (r = 0.592, P < 0.003), and negatively correlated with
      incidence of de novo or worsening of mild MR (r =-0.78, -0.93, P < 0.001). The
      regression analyses revealed that PMVL/AMVL ratio is the best and a reliable
      predictor of success and outcome of BMV, hazard ratio (95% confidence interval)
      0.12 (0.05-52), P < 0.001. CONCLUSION: Length ratio of PMVL/AMVL assessment with
      echocardiography is an excellent simple predictor of post-BMV mitral valve area
      and the cardiac events.

PMID- 21966897
TI  - Metabolomics in paediatric respiratory diseases and bronchiolitis.
AB  - The metabolic study of an organism may make it possible to monitor, through the
      metabolites,the physiology and/or pathology of the organism itself. Metabolomics,
      in the strictest sense, "the set of metabolites, the final products of the
      genetic expression". Most clinical chemistry tests available today rely on old
      technologies that measure only a single chemical in blood, urine or other
      biofluids, and these tests are neither sensitive nor specific for any particular
      disease. Metabolomics offers a holistic approach to systems medicine, with the
      promise to enhance clinical chemistry diagnostics in several pathologic
      conditions. The present review covers the application of clinical metabolomics in
      three different areas of respiratory diseases in pediatrics: asthma, pneumonia
      and bronchiolitis. Comparison between two 1H-NMR urine spectra by two
      bronchiolitis patients are also presented.

PMID- 21966898
TI  - MUC1 in mesenchymal-to-epithelial transition during human nephrogenesis: changing
      the fate of renal progenitor/stem cells?
AB  - BACKGROUND: The development of the human kidney is a complex process requiring
      interactions between epithelial and mesenchymal cells. The condensed cap
      mesenchyme is hypothesized to generate a population of stem/progenitor cells that
      undergo mesenchymal-epithelial transition (MET) originating nephrons. Few
      immunohistochemical markers are available for detecting cap mesenchymal cells in
      the early phases of MET. METHODS: The expression of MUC1 was evaluated in the
      kidneys, of 4 human foetuses and 2 newborns. RESULTS: MUC1 immunoreactivity was
      detected in all the examined kidneys in the cap mesenchyme and in the renal
      vesicles. Immunostaining for MUC1 in cap mesenchymal cells changed from one
      nodule to the next: some mesenchymal nodules were negative, some showed MUC1
      reactivity in scattered cells, whereas in others, positive cells revealed the
      presence of a roundish developing epithelial structure. CONCLUSIONS: Our data
      clearly indicates, for the first time to the best of our knowledge,
      immunohistochemical evidence of MUC1 expression during human kidney development.
      We focused on MUC1 reactivity in the cap mesenchyme. On the basis of these
      preliminary data, we speculate that MUC1 may be involved in human nephrogenesis
      and may play a relevant role in MET from the cap mesenchyme to the renal vesicle,
      changing the fate of renal stem/progenitor cells.

PMID- 21966899
TI  - Primary and reactivated HHV8 infection and disease after liver transplantation: a
      prospective study.
AB  - Human herpesvirus 8 (HHV8) is pathogenic in humans, especially in cases of
      immunosuppression. We evaluated the risk of HHV8 transmission from liver donors,
      and its clinical impact in southern Italy, where its seroprevalence in the
      general population is reported to be as high as 18.3%. We tested 179 liver
      transplant recipients and their donors for HHV8 antibodies at the time of
      transplantation, and implemented in all recipients a 12-month posttransplant
      surveillance program for HHV8 infection. Of the 179 liver transplant recipients
      enrolled, 10.6% were HHV8 seropositive before transplantation, whereas the organ
      donor's seroprevalence was 4.4%. Eight seronegative patients received a liver
      from a seropositive donor, and four of them developed primary HHV8 infection. Two
      of these patients had lethal nonmalignant illness with systemic involvement and
      multiorgan failure. Among the 19 HHV8 seropositive recipients, two had viral
      reactivation after liver transplantation. In addition, an HHV8 seronegative
      recipient of a seronegative donor developed primary HHV8 infection and
      multicentric Castleman's disease. In conclusion, primary HHV8 infection
      transmitted from a seropositive donor to a seronegative liver transplant
      recipient can cause a severe nonmalignant illness associated with high mortality.
      Donor screening for HHV8 should be considered in geographic areas with a high
      prevalence of such infection.

PMID- 21966900
TI  - Childhood epidermolysis bullosa acquisita: report of a Chinese case.
AB  - Epidermolysis bullosa acquisita (EBA) is a rare, acquired, subepidermal
      blistering disease characterized by autoantibodies directed against type VII
      collagen, the major component of anchoring fibrils. We report a 5-year-old
      Chinese boy who presented with extensive lesions consisting of disseminated
      pruritic vesicles and tense blisters. The diagnosis of EBA was confirmed by
      histopathology, immunofluorescence, and immunoblotting analysis. The disease was
      controlled with a combination of prednisone and dapsone.

PMID- 21966901
TI  - Control of biofilm formation and colonization in Vibrio fischeri: a role for
      partner switching?
AB  - Bacteria employ a variety of mechanisms to promote and control colonization of
      their respective hosts, including restricting the expression of genes necessary
      for colonization to distinct situations (i.e. encounter with a prospective host).
      In the symbiosis between the marine bacterium Vibrio fischeri and its host squid,
      Euprymna scolopes, colonization proceeds via a transient biofilm formed by the
      bacterium. The production of this bacterial biofilm depends on a complex
      regulatory network that controls transcription of the symbiosis polysaccharide
      (syp) gene locus. In addition to this transcriptional control, biofilm formation
      is regulated by two proteins, SypA and SypE, which may function in an unusual
      regulatory mechanism known as partner switching. Best characterized in Bacillus
      subtilis and other Gram-positive bacteria, partner switching is a signalling
      mechanism that provides dynamic regulatory control over bacterial gene
      expression. The involvement of putative partner-switching components within V.
      fischeri suggests that tight regulatory control over biofilm formation may be
      important for the lifestyle of this organism.

PMID- 21966902
TI  - Dynamics of genome evolution in facultative symbionts of aphids.
AB  - Aphids are sap-feeding insects that host a range of bacterial endosymbionts
      including the obligate, nutritional mutualist Buchnera plus several bacteria that
      are not required for host survival. Among the latter, 'Candidatus Regiella
      insecticola' and 'Candidatus Hamiltonella defensa' are found in pea aphids and
      other hosts and have been shown to protect aphids from natural enemies. We have
      sequenced almost the entire genome of R. insecticola (2.07 Mbp) and compared it
      with the recently published genome of H. defensa (2.11 Mbp). Despite being sister
      species the two genomes are highly rearranged and the genomes only have ~55% of
      genes in common. The functions encoded by the shared genes imply that the
      bacteria have similar metabolic capabilities, including only two essential amino
      acid biosynthetic pathways and active uptake mechanisms for the remaining eight,
      and similar capacities for host cell toxicity and invasion (type 3 secretion
      systems and RTX toxins). These observations, combined with high sequence
      divergence of orthologues, strongly suggest an ancient divergence after
      establishment of a symbiotic lifestyle. The divergence in gene sets and in genome
      architecture implies a history of rampant recombination and gene inactivation and
      the ongoing integration of mobile DNA (insertion sequence elements, prophage and
      plasmids).

PMID- 21966903
TI  - Deep sequencing reveals exceptional diversity and modes of transmission for
      bacterial sponge symbionts.
AB  - Marine sponges contain complex bacterial communities of considerable ecological
      and biotechnological importance, with many of these organisms postulated to be
      specific to sponge hosts. Testing this hypothesis in light of the recent
      discovery of the rare microbial biosphere, we investigated three Australian
      sponges by massively parallel 16S rRNA gene tag pyrosequencing. Here we show
      bacterial diversity that is unparalleled in an invertebrate host, with more than
      250,000 sponge-derived sequence tags being assigned to 23 bacterial phyla and
      revealing up to 2996 operational taxonomic units (95% sequence similarity) per
      sponge species. Of the 33 previously described 'sponge-specific' clusters that
      were detected in this study, 48% were found exclusively in adults and larvae -
      implying vertical transmission of these groups. The remaining taxa, including
      'Poribacteria', were also found at very low abundance among the 135,000 tags
      retrieved from surrounding seawater. Thus, members of the rare seawater biosphere
      may serve as seed organisms for widely occurring symbiont populations in sponges
      and their host association might have evolved much more recently than previously
      thought.

PMID- 21966904
TI  - Endobacteria affect the metabolic profile of their host Gigaspora margarita, an
      arbuscular mycorrhizal fungus.
AB  - The aim of this paper was to understand whether the endobacterium identified as
      Candidatus Glomeribacter gigasporarum has an effect on the biology of its host,
      the arbuscular mycorrhizal fungus Gigaspora margarita, through the study of the
      modifications induced on the fungal proteome and lipid profile. The availability
      of G. margarita cured spores (i.e. spores that do not contain bacteria),
      represented a crucial tool to enable the comparison between two fungal
      homogeneous populations in the presence and the absence of the bacterial
      components. Our results demonstrate that the endobacterial presence leads to a
      modulation of fungal protein expression in all the different conditions we tested
      (quiescent, germinating and strigolactone-elicited germinating spores), and in
      particular after treatment with a strigolactone analogue. The fungal fatty acid
      profile resulted to be modified both quantitatively and qualitatively in the
      absence of endobacteria, being fatty acids less abundant in the cured spores. The
      results offer one of the first comparative metabolic studies of an AM fungus
      investigated under different physiological conditions, reveal that endobacteria
      have an important impact on the host fungal activity, influencing both protein
      expression and lipid profile, and suggest that the bacterial absence is perceived
      by G. margarita as a stimulus which activates stress-responsive proteins.

PMID- 21966905
TI  - Influences of space, soil, nematodes and plants on microbial community
      composition of chalk grassland soils.
AB  - Microbial communities respond to a variety of environmental factors related to
      resources (e.g. plant and soil organic matter), habitat (e.g. soil
      characteristics) and predation (e.g. nematodes, protozoa and viruses). However,
      the relative contribution of these factors on microbial community composition is
      poorly understood. Here, we sampled soils from 30 chalk grassland fields located
      in three different chalk hill ridges of Southern England, using a spatially
      explicit sampling scheme. We assessed microbial communities via phospholipid
      fatty acid (PLFA) analyses and PCR-denaturing gradient gel electrophoresis (DGGE)
      and measured soil characteristics, as well as nematode and plant community
      composition. The relative influences of space, soil, vegetation and nematodes on
      soil microorganisms were contrasted using variation partitioning and path
      analysis. Results indicate that soil characteristics and plant community
      composition, representing habitat and resources, shape soil microbial community
      composition, whereas the influence of nematodes, a potential predation factor,
      appears to be relatively small. Spatial variation in microbial community
      structure was detected at broad (between fields) and fine (within fields) scales,
      suggesting that microbial communities exhibit biogeographic patterns at different
      scales. Although our analysis included several relevant explanatory data sets, a
      large part of the variation in microbial communities remained unexplained (up to
      92% in some analyses). However, in several analyses, significant parts of the
      variation in microbial community structure could be explained. The results of
      this study contribute to our understanding of the relative importance of
      different environmental and spatial factors in driving the composition of soil
      borne microbial communities.

PMID- 21966906
TI  - An ectobiont-bearing foraminiferan, Bolivina pacifica, that inhabits microxic
      pore waters: cell-biological and paleoceanographic insights.
AB  - The presence of tests (shells) in foraminifera could be taken as an indicator
      that this protist taxon is unlikely to possess ectosymbionts. Here, however, we
      describe an association between Bolivina pacifica, a foraminiferan with a
      calcareous test, and a rod-shaped microbe (bacterium or archaeon) that is
      directly associated with the pores of the foraminiferan's test. In addition to
      these putative ectosymbionts, B. pacifica has previously undescribed cytoplasmic
      plasma membrane invaginations (PMIs). These adaptations (i.e. PMIs, ectobionts),
      along with the clustering of mitochondria under the pores and at the cell
      periphery, suggest active exchange between the host and ectobiont. The B.
      pacifica specimens examined were collected from sediments overlain by oxygen
      depleted bottom waters (0.7 MUM) of the Santa Barbara Basin (California, USA). An
      ultrastructural comparison between B. pacifica from the Santa Barbara Basin and a
      congener (Bolivina cf. B. lanceolata) collected from well-oxygenated sediments
      (Florida Keys) suggests that PMIs, ectobionts and peripherally distributed
      mitochondria are all factors that promote inhabitation of microxic environments
      by B. pacifica. The calcitic delta(13)C signatures of B. pacifica and of a co
      occurring congener (B. argentea) that lacks ectobionts differ by > 1.50/00,
      raising the possibility that the presence of ectobionts can affect incorporation
      of paleoceanographic proxies.

PMID- 21966907
TI  - Strict cospeciation of devescovinid flagellates and Bacteroidales ectosymbionts
      in the gut of dry-wood termites (Kalotermitidae).
AB  - The surface of many termite gut flagellates is colonized with a dense layer of
      bacteria, yet little is known about the evolutionary relationships of such
      ectosymbionts and their hosts. Here we investigated the molecular phylogenies of
      devescovinid flagellates (Devescovina spp.) and their symbionts from a wide range
      of dry-wood termites (Kalotermitidae). From species-pure flagellate suspensions
      isolated with micropipettes, we obtained SSU rRNA gene sequences of symbionts and
      host. Phylogenetic analysis showed that the Devescovina spp. present in many
      species of Kalotermitidae form a monophyletic group, which includes also the
      unique devescovinid flagellate Caduceia versatilis. All members of this group
      were consistently associated with a distinct lineage of Bacteroidales, whose
      location on the cell surface was confirmed by fluorescence in situ hybridization.
      The well-supported congruence of the phylogenies of devescovinids and their
      ectosymbionts documents a strict cospeciation. In contrast, the endosymbionts of
      the same flagellates ('Endomicrobia') were clearly polyphyletic and must have
      been acquired independently by horizontal transfer from other flagellate
      lineages. Also the Bacteroidales ectosymbionts of Oxymonas flagellates present in
      several Kalotermitidae belonged to several distantly related lines of descent,
      underscoring the general perception that the evolutionary history of flagellate
      bacteria symbioses in the termite gut is complex.

PMID- 21966908
TI  - Zn pollution counteracts Cd toxicity in metal-tolerant ectomycorrhizal fungi and
      their host plant, Pinus sylvestris.
AB  - Adaptive Zn and Cd tolerance have evolved in populations of the ectomycorrhizal
      fungus Suillus luteus. When exposed to high concentrations of both metals in
      vitro, a one-sided antagonism was apparent in the Zn- and Cd-tolerant isolates.
      Addition of high Zn concentrations restored growth of Cd-stressed isolates, but
      not vice versa. The antagonistic effect was not detected in a S. luteus isolate
      from non-contaminated land and in Paxillus involutus. The fungi were inoculated
      on pine seedlings and subsequently exposed to ecologically relevant Zn and Cd
      concentrations in single and mixed treatments. The applied doses severely reduced
      nutrient acquisition of non-mycorrhizal pines and pines inoculated with metal
      sensitive S. luteus. Highest translocation of Zn and Cd to shoots occurred in the
      same plants. Seedlings inoculated with fungi collected from the polluted site
      reduced metal transfer to their host and maintained nutrient acquisition under
      high metal exposure. The isolate showing highest tolerance in vitro also offered
      best protection in symbiosis. The antagonistic effect of high Zn on Cd toxicity
      was confirmed in the plant experiment. The results indicate that a Zn- and Cd
      polluted soil has selected ectomycorrhizal fungi that are able to survive and
      protect their phytobiont from nutrient starvation and excessive metal uptake.

PMID- 21966909
TI  - Diversity and host specificity of the Verminephrobacter-earthworm symbiosis.
AB  - Symbiotic bacteria of the genus Verminephrobacter (Betaproteobacteria) were
      detected in the nephridia of 19 out of 23 investigated earthworm species
      (Oligochaeta: Lumbricidae) by 16S rRNA gene sequence analysis and fluorescence in
      situ hybridization (FISH). While all four Lumbricus species and three out of five
      Aporrectodea species were densely colonized by a mono-species culture of
      Verminephrobacter, other earthworm species contained mixed bacterial populations
      with varying proportions of Verminephrobacter; four species did not contain
      Verminephrobacter at all. The Verminephrobacter symbionts could be grouped into
      earthworm species-specific sequence clusters based on their 16S rRNA and RNA
      polymerase subunit B (rpoB) genes. Closely related host species harboured more
      closely related symbionts than did distantly related hosts. Co-diversification of
      the symbiotic partners could not be demonstrated unambiguously due to the poor
      resolution of the host phylogeny [based on histone H3 and cytochrome c oxidase
      subunit I (COI) gene sequence analyses]. However, there was a pattern of symbiont
      diversification within four groups of closely related hosts. The mean rate of
      symbiont 16S rRNA gene evolution was determined using a relaxed clock model, and
      the rate was calibrated with paleogeographical estimates of the time of origin of
      Lumbricid earthworms. The calibrated rates of symbiont 16S rRNA gene evolution
      are 0.012-0.026 substitutions per site per 50 million years and thus similar to
      rates reported from other symbiotic bacteria.

PMID- 21966912
TI  - Radiocesium transfer between Medicago truncatula plants via a common mycorrhizal
      network.
AB  - Common mycorrhizal networks of arbuscular mycorrhizal fungi have been reported to
      transfer cesium between plants. However, a direct hyphae-mediated transfer (via
      cytoplasm/protoplasm) cannot be distinguished from an indirect transfer. Indeed,
      cesium released by the roots of the donor plant can be taken up by the receiver
      plant or fungal hyphae. In the present study, Medicago truncatula plants were
      connected by a common mycorrhizal network and Prussian Blue (ammonium-ferric
      hexacyano ferrate) was added in the growth medium to adsorb the released
      radiocesium. A direct transfer of radiocesium to roots and shoots of the receiver
      plant was clearly demonstrated for the first time. Even though this transfer was
      quantitatively low, it suggested that shared mycorrhizal networks could
      contribute to the redistribution of this radionuclide in the environment, which
      otherwise would be restricted both in time and space. This finding may also help
      to understand the behaviour of its chemical analogue, potassium.

PMID- 21966913
TI  - Taming the symbiont for coexistence: a host PGRP neutralizes a bacterial symbiont
      toxin.
AB  - In horizontally transmitted mutualisms between marine animals and their bacterial
      partners, the host environment promotes the initial colonization by specific
      symbionts that it harvests from the surrounding bacterioplankton. Subsequently,
      the host must develop long-term tolerance to immunogenic bacterial molecules,
      such as peptidoglycan and lipopolysaccaride derivatives. We describe the
      characterization of the activity of a host peptidoglycan recognition protein
      (EsPGRP2) during establishment of the symbiosis between the squid Euprymna
      scolopes and its luminous bacterial symbiont Vibrio fischeri. Using confocal
      immunocytochemistry, we localized EsPGRP2 to all epithelial surfaces of the
      animal, and determined that it is exported in association with mucus shedding.
      Most notably, EsPGRP2 was released by the crypt epithelia into the extracellular
      spaces housing the symbionts. This translocation occurred only after the
      symbionts had triggered host morphogenesis, a process that is induced by exposure
      to the peptidoglycan monomer tracheal cytotoxin (TCT), a bacterial 'toxin' that
      is constitutively exported by V. fischeri. Enzymatic analyses demonstrated that,
      like many described PGRPs, EsPGRP2 has a TCT-degrading amidase activity. The
      timing of EsPGRP2 export into the crypts provides evidence that the host does not
      export this protein until after TCT induces morphogenesis, and thereafter EsPGRP2
      is constantly present in the crypts ameliorating the effects of V. fischeri TCT.

PMID- 21966914
TI  - Dual symbiosis of the vent shrimp Rimicaris exoculata with filamentous gamma- and
      epsilonproteobacteria at four Mid-Atlantic Ridge hydrothermal vent fields.
AB  - The shrimp Rimicaris exoculata from hydrothermal vents on the Mid-Atlantic Ridge
      (MAR) harbours bacterial epibionts on specialized appendages and the inner
      surfaces of its gill chamber. Using comparative 16S rRNA sequence analysis and
      fluorescence in situ hybridization (FISH), we examined the R. exoculata epibiosis
      from four vents sites along the known distribution range of the shrimp on the
      MAR. Our results show that R. exoculata lives in symbiosis with two types of
      filamentous epibionts. One belongs to the Epsilonproteobacteria, and was
      previously identified as the dominant symbiont of R. exoculata. The second is a
      novel gammaproteobacterial symbiont that belongs to a clade consisting
      exclusively of sequences from epibiotic bacteria of hydrothermal vent animals,
      with the filamentous sulfur oxidizer Leucothrix mucor as the closest free-living
      relative. Both the epsilon- and the gammaproteobacterial symbionts dominated the
      R. exoculata epibiosis at all four MAR vent sites despite striking differences
      between vent fluid chemistry and distances between sites of up to 8500 km,
      indicating that the symbiosis is highly stable and specific. Phylogenetic
      analyses of two mitochondrial host genes showed little to no differences between
      hosts from the four vent sites. In contrast, there was significant spatial
      structuring of both the gamma- and the epsilonproteobacterial symbiont
      populations based on their 16S rRNA gene sequences that was correlated with
      geographic distance along the MAR. We hypothesize that biogeography and host
      symbiont selectivity play a role in structuring the epibiosis of R. exoculata.

PMID- 21966915
TI  - Multi-host ectomycorrhizal fungi are predominant in a Guinean tropical rainforest
      and shared between canopy trees and seedlings.
AB  - The diversity of ectomycorrhizal (ECM) fungi on adult trees and seedlings of five
      species, Anthonotha fragrans, Anthonotha macrophylla, Cryptosepalum tetraphyllum,
      Paramacrolobium coeruleum and Uapaca esculenta, was determined in a tropical rain
      forest of Guinea. Ectomycorrhizae were sampled within a surface area of 1600
      m(2), and fungal taxa were identified by sequencing the rDNA Internal Transcribed
      Spacer region. Thirty-nine ECM fungal taxa were determined, of which 19 multi
      hosts, 9 single-hosts and 11 singletons. The multi-host fungi represented 92%
      (89% when including the singletons in the analysis) of the total abundance.
      Except for A. fragrans, the adults of the host species displayed significant
      differentiation for their fungal communities, but their seedlings harboured a
      similar fungal community. These findings suggest that there was a potential for
      the formation of common mycorrhizal networks in close vicinity. However, no
      significant difference was detected for the delta(13)C and delta(15)N values
      between seedlings and adults of each ECM plant, and no ECM species exhibited
      signatures of mixotrophy. Our results revealed (i) variation in ECM fungal
      diversity according to the seedling versus adult development stage of trees and
      (ii) low host specificity of ECM fungi, and indicated that multi-host fungi are
      more abundant than single-host fungi in this forest stand.

PMID- 21966916
TI  - Herbaspirillum seropedicae rfbB and rfbC genes are required for maize
      colonization.
AB  - In this study we disrupted two Herbaspirillum seropedicae genes, rfbB and rfbC,
      responsible for rhamnose biosynthesis and its incoporation into LPS. GC-MS
      analysis of the H. seropedicae wild-type strain LPS oligosaccharide chain showed
      that rhamnose, glucose and N-acetyl glucosamine are the predominant
      monosaccharides, whereas rhamnose and N-acetyl glucosamine were not found in the
      rfbB and rfbC strains. The electrophoretic pattern of the mutants LPS was
      drastically altered when compared with the wild type. Knockout of rfbB or rfbC
      increased the sensitivity towards SDS, polymyxin B sulfate and salicylic acid.
      The mutants attachment capacity to maize root surface plantlets was 100-fold
      lower than the wild type. Interestingly, the wild-type capacity to attach to
      maize roots was reduced to a level similar to that of the mutants when the assay
      was performed in the presence of isolated wild-type LPS, glucosamine or N-acetyl
      glucosamine. The mutant strains were also significantly less efficient in
      endophytic colonization of maize. Expression analysis indicated that the rfbB
      gene is upregulated by naringenin, apigenin and CaCl(2). Together, the results
      suggest that intact LPS is required for H. seropedicae attachment to maize root
      and internal colonization of plant tissues.

PMID- 21966911
TI  - Disclosing arbuscular mycorrhizal fungal biodiversity in soil through a land-use
      gradient using a pyrosequencing approach.
AB  - The biodiversity of arbuscular mycorrhizal fungi (AMF) communities present in
      five Sardinian soils (Italy) subjected to different land-use (tilled vineyard,
      covered vineyard, pasture, managed meadow and cork-oak formation) was analysed
      using a pyrosequencing-based approach for the first time. Two regions of the 18S
      ribosomal RNA gene were considered as molecular target. The pyrosequencing
      produced a total of 10924 sequences: 6799 from the first and 4125 from the second
      target region. Among these sequences, 3189 and 1003 were selected to generate
      operational taxonomic units (OTUs) and to evaluate the AMF community richness and
      similarity: 117 (37 of which were singletons) and 28 (nine of which were
      singletons) unique AMF OTUs were detected respectively. Within the Glomeromycota
      OTUs, those belonging to the Glomerales order were dominant in all the soils.
      Diversisporales OTUs were always detected, even though less frequently, while
      Archaeosporales and Paraglomerales OTUs were exclusive of the pasture soil.
      Eleven OTUs were shared by all the soils, but each of the five AMF communities
      showed particular features, suggesting a meaningful dissimilarity among the
      Glomeromycota populations. The environments with low inputs (pasture and covered
      vineyard) showed a higher AMF biodiversity than those subjected to human input
      (managed meadow and tilled vineyard). A reduction in AMF was found in the cork
      oak formation because other mycorrhizal fungal species, more likely associated to
      trees and shrubs, were detected. These findings reinforce the view that AMF
      biodiversity is influenced by both human input and ecological traits,
      illustrating a gradient of AMF communities which mirror the land-use gradient.
      The high number of sequences obtained by the pyrosequencing strategy has provided
      detailed information on the soil AMF assemblages, thus offering a source of light
      to shine on this crucial soil microbial group.

PMID- 21966910
TI  - Diversity analyses of Aeschynomene symbionts in Tropical Africa and Central
      America reveal that nod-independent stem nodulation is not restricted to
      photosynthetic bradyrhizobia.
AB  - Tropical aquatic legumes of the genus Aeschynomene are unique in that they can be
      stem-nodulated by photosynthetic bradyrhizobia. Moreover, a recent study
      demonstrated that two Aeschynomene indica symbionts lack canonical nod genes,
      thereby raising questions about the distribution of such atypical symbioses among
      rhizobial-legume interactions. Population structure and genomic diversity were
      compared among stem-nodulating bradyrhizobia isolated from various Aeschynomene
      species of Central America and Tropical Africa. Phylogenetic analyses based on
      the recA gene and whole-genome amplified fragment length polymorphism (AFLP)
      fingerprints on 110 bacterial strains highlighted that all the photosynthetic
      strains form a separate cluster among bradyrhizobia, with no obvious structuring
      according to their geographical or plant origins. Nod-independent symbiosis was
      present in all sampling areas and seemed to be linked to Aeschynomene host
      species. However, it was not strictly dependent on photosynthetic ability, as
      exemplified by a newly identified cluster of strains that lacked canonical nod
      genes and efficiently stem-nodulated A. indica, but were not photosynthetic.
      Interestingly, the phenotypic properties of this new cluster of bacteria were
      reflected by their phylogenetical position, as being intermediate in distance
      between classical root-nodulatingBradyrhizobium spp. and photosynthetic ones.
      This result opens new prospects about stem-nodulating bradyrhizobial evolution.

PMID- 21966917
TI  - Selenium controls transcription of paralogous formate dehydrogenase genes in the
      termite gut acetogen, Treponema primitia.
AB  - The termite gut spirochete, Treponema primitia, is a CO(2)-reductive acetogen
      that is phylogenetically distinct from other distantly related and more
      extensively studied acetogens such as Moorella thermoacetica. Research on T.
      primitia has revealed details about the role of spirochetes in CO(2)-reductive
      acetogenesis, a process important to the mutualism occurring between termites and
      their gut microbial communities. Here, a locus of the T. primitia genome
      containing Wood-Ljungdahl pathway genes for CO(2)-reductive acetogenesis was
      sequenced. This locus contained methyl-branch genes of the pathway (i.e. for the
      reduction of CO(2) to the level of methyl-tetrahydrofolate) including paralogous
      genes for cysteine and selenocysteine (Sec) variants of formate dehydrogenase
      (FDH) and genes for Sec incorporation. The FDH variants affiliated
      phylogenetically with hydrogenase-linked FDH enzymes, suggesting that T. primitia
      FDH enzymes utilize electrons derived directly from molecular H(2). Sub-nanomolar
      concentrations of selenium decreased transcript levels of the cysteine variant
      FDH gene. Selenium concentration did not markedly influence the level of mRNA
      upstream of the Sec-codon in the Sec variant FDH; however, the level of
      transcript extending downstream of the Sec-codon increased incrementally with
      increasing selenium concentrations. The features and regulation of these FDH
      genes are an indication that T. primitia may experience dynamic selenium
      availability in its H(2)-rich gut environment.

PMID- 21966918
TI  - Expression-based identification of genetic determinants of the bacterial
      symbiosis 'Chlorochromatium aggregatum'.
AB  - The phototrophic consortium 'Chlorochromatium aggregatum' is a highly structured
      association of green sulfur bacterial epibionts surrounding a central, motile
      bacterium and is the most specific symbiosis currently known between two
      phylogenetically distinct bacterial species. Genes and gene products potentially
      involved in the symbiotic interaction were identified on the genomic,
      transcriptomic and proteomic level. As compared with the 11 available genomes of
      free-living relatives, only 186 open reading frames were found to be unique to
      the epibiont genome. 2-D differential gel electrophoresis (2-D DIGE) of the
      soluble proteomes recovered 1612 protein spots of which 54 were detected
      exclusively in consortia but not in pure epibiont cultures. Using mass
      spectrometry analyses, the 13 most intense of the 54 spots could be attributed to
      the epibiont. Analyses of the membrane proteins of consortia, of consortia
      treated with cross-linkers and of pure cultures indicated that a branched chain
      amino acid ABC-transporter binding protein is only expressed in the symbiotic
      state of the epibiont. Furthermore, analyses of chlorosomes revealed that an
      uncharacterized 11 kDa epibiont protein is only expressed during symbiosis. This
      protein may be involved in the intracellular sorting of chlorosomes. Application
      of a novel prokaryotic cDNA suppression subtractive hybridization technique led
      to identification of 14 differentially regulated genes, and comparison of the
      transcriptomes of symbiotic and free-living epibionts indicated that 328 genes
      were differentially transcribed. The three approaches were mostly complementary
      and thereby yielded a first inventory of 352 genes that are likely to be involved
      in the bacterial interaction in 'C. aggregatum'. Notably, most of the regulated
      genes encoded components of central metabolic pathways whereas only very few
      (7.5%) of the unique 'symbiosis genes' turned out to be regulated under the
      experimental conditions tested. This pronounced regulation of central metabolic
      pathways may serve to fine-tune the symbiotic interaction in 'C. aggregatum' in
      response to environmental conditions.

PMID- 21966919
TI  - Transmission of a bacterial consortium in Eisenia fetida egg capsules.
AB  - The earthworm Eisenia fetida harbours Verminephrobacter eiseniae within their
      excretory nephridia. This symbiont is transferred from the parent into the egg
      capsules where the cells are acquired by the developing earthworm in a series of
      recruitment steps. Previous studies defined V. eiseniae as the most abundant cell
      type in the egg capsules, leaving approximately 30% of the bacteria unidentified
      and of unknown origin. The study presented here used terminal restriction
      fragment length polymorphism analysis together with cloning and sequencing of 16S
      rRNA genes to define the composition of the bacterial consortium in E. fetida egg
      capsules from early to late development. Newly formed capsules of E. fetida
      contained three bacterial types, a novel Microbacteriaceae member, a
      Flexibacteriaceae member and the previously described V. eiseniae. Fluorescent in
      situ hybridization (FISH) using specific and general rRNA probes demonstrated
      that the bacteria are abundant during early development, colonize the embryo and
      appear in the adult nephridia. As the capsules mature, Herbaspirillum spp. become
      abundant although they were not detected within the adult worm. These divergent
      taxa could serve distinct functions in both the adult earthworm and in the egg
      capsule to influence the competitive ability of earthworms within the soil
      community.

PMID- 21966920
TI  - The genome of Syntrophomonas wolfei: new insights into syntrophic metabolism and
      biohydrogen production.
AB  - Syntrophomonas wolfei is a specialist, evolutionarily adapted for syntrophic
      growth with methanogens and other hydrogen- and/or formate-using microorganisms.
      This slow-growing anaerobe has three putative ribosome RNA operons, each of which
      has 16S rRNA and 23S rRNA genes of different length and multiple 5S rRNA genes.
      The genome also contains 10 RNA-directed, DNA polymerase genes. Genomic analysis
      shows that S. wolfei relies solely on the reduction of protons, bicarbonate or
      unsaturated fatty acids to re-oxidize reduced cofactors. Syntrophomonas wolfei
      lacks the genes needed for aerobic or anaerobic respiration and has an
      exceptionally limited ability to create ion gradients. An ATP synthase and a
      pyrophosphatase were the only systems detected capable of creating an ion
      gradient. Multiple homologues for beta-oxidation genes were present even though
      S. wolfei uses a limited range of fatty acids from four to eight carbons in
      length.Syntrophomonas wolfei, other syntrophic metabolizers with completed
      genomic sequences, and thermophilic anaerobes known to produce high molar ratios
      of hydrogen from glucose have genes to produce H(2) from NADH by an electron
      bifurcation mechanism. Comparative genomic analysis also suggests that formate
      production from NADH may involve electron bifurcation. A membrane-bound, iron
      sulfur oxidoreductase found in S. wolfei and Syntrophus aciditrophicus may be
      uniquely involved in reverse electron transport during syntrophic fatty acid
      metabolism. The genome sequence of S. wolfei reveals several core reactions that
      may be characteristic of syntrophic fatty acid metabolism and illustrates how
      biological systems produce hydrogen from thermodynamically difficult reactions.

PMID- 21966921
TI  - Natural transformation of Vibrio fischeri requires tfoX and tfoY.
AB  - Recent evidence has indicated that natural genetic transformation occurs in
      Vibrio cholerae, and that it requires both induction by chitin oligosaccharides,
      like chitohexaose, and expression of a putative regulatory gene designated tfoX.
      Using sequence and phylogenetic analyses we have found two tfoX paralogues in all
      sequenced genomes of the genus Vibrio. Like V. cholerae, when grown in
      chitohexaose, cells of V. fischeri are able to take up and incorporate exogenous
      DNA. Chitohexaose-independent transformation by V. fischeri was observed when
      tfoX was present in multicopy. The second tfoX paralogue, designated tfoY, is
      also required for efficient transformation in V. fischeri, but is not
      functionally identical to tfoX. Natural transformation of V. fischeri facilitates
      rapid transfer of mutations across strains, and provides a highly useful tool for
      experimental genetic manipulation in this species. The presence of chitin-induced
      competence in several vibrios highlights the potential for a conserved mechanism
      of genetic exchange across this family of environmentally important marine
      bacteria.

PMID- 21966922
TI  - Gamma- and epsilonproteobacterial ectosymbionts of a shallow-water marine worm
      are related to deep-sea hydrothermal vent ectosymbionts.
AB  - The marine oligochaete worm Tubificoides benedii is often found in high numbers
      in eutrophic coastal sediments with low oxygen and high sulfide concentrations. A
      dense biofilm of filamentous bacteria on the worm's tail end were morphologically
      described over 20 years ago, but no further studies of these epibiotic
      associations were done. In this study, we used fluorescence in situ hybridization
      and comparative sequence analysis of 16S rRNA and protein-coding genes to
      characterize the microbial community of the worm's tail ends. The presence of
      genes involved in chemoautotrophy (cbbL and cbbM) and sulfur metabolism (aprA)
      indicated the potential of the T. benedii microbial community for chemosynthesis.
      Two filamentous ectosymbionts were specific to the worm's tail ends: one belonged
      to the Leucothrix mucor clade within the Gammaproteobacteria and the other to the
      Thiovulgaceae within the Epsilonproteobacteria. Both T. benedii ectosymbionts
      belonged to clades that consisted almost exclusively of bacteria associated with
      invertebrates from deep-sea hydrothermal vents. Such close relationships between
      symbionts from shallow-water and deep-sea hosts that are not closely related to
      each other are unusual, and indicate that biogeography and host affiliation did
      not play a role in these associations. Instead, similarities between the dynamic
      environments of vents and organic-rich mudflats with their strong fluctuations in
      reductants and oxidants may have been the driving force behind the establishment
      and evolution of these symbioses.

PMID- 21966923
TI  - Identification of the dominant sulfate-reducing bacterial partner of anaerobic
      methanotrophs of the ANME-2 clade.
AB  - The anaerobic oxidation of methane (AOM) with sulfate as terminal electron
      acceptor is mediated by consortia of methanotrophic archaea (ANME) and sulfate
      reducing bacteria (SRB). Whereas three clades of ANME have been repeatedly
      studied with respect to phylogeny, key genes and genomic capabilities, little is
      known about their sulfate-reducing partner. In order to identify the partner of
      anaerobic methanotrophs of the ANME-2 clade, bacterial 16S rRNA gene libraries
      were constructed from cultures highly enriched for ANME-2a and ANME-2c in
      consortia with Deltaproteobacteria of the Desulfosarcina/Desulfococcus group
      (DSS). Phylogenetic analysis of those and publicly available sequences from AOM
      sites supported the hypothesis by Knittel and colleagues that the DSS partner
      belongs to the diverse SEEP-SRB1 cluster. Six subclusters of SEEP-SRB1, SEEP
      SRB1a to SEEP-SRB1f, were proposed and specific oligonucleotide probes were
      designed. Using fluorescence in situ hybridization on samples from six different
      AOM sites, SEEP-SRB1a was identified as sulfate-reducing partner in up to 95% of
      total ANME-2 consortia. SEEP-SRB1a cells exhibited a rod-shaped, vibrioid, or
      coccoid morphology and were found to be associated with subgroups ANME-2a and
      ANME-2c. Moreover, SEEP-SRB1a was also detected in 8% to 23% of ANME-3 consortia
      in Haakon Mosby Mud Volcano sediments, previously described to be predominantly
      associated with SRB of the Desulfobulbus group. SEEP-SRB1a contributed to only
      0.3% to 0.7% of all single cells in almost all samples indicating that these
      bacteria are highly adapted to a symbiotic relationship with ANME-2.

PMID- 21966924
TI  - Thermoanaerobacteriaceae oxidize acetate in methanogenic rice field soil at 50
      degrees C.
AB  - Rice field soils contain a thermophilic microbial community. Incubation of
      Italian rice field soil at 50 degrees C resulted in transient accumulation of
      acetate, but the microorganisms responsible for methane production from acetate
      are unknown. Without addition of exogenous acetate, the delta(13)C of CH(4) and
      CO(2) indicated that CH(4) was exclusively produced by hydrogenotrophic
      methanogenesis. When exogenous acetate was added, acetoclastic methanogenesis
      apparently also operated. Nevertheless, addition of [2-(13)C]acetate (99% (13)C)
      resulted in the production not only of (13)C-labelled CH(4) but also of CO(2),
      which contained up to 27% (13)C, demonstrating that the methyl group of acetate
      was also oxidized. Part of the (13)C-labelled acetate was also converted to
      propionate which contained up to 14% (13)C. The microorganisms capable of
      assimilating acetate at 50 degrees C were targeted by stable isotope probing
      (SIP) of ribosomal RNA and rRNA genes using [U-(13)C] acetate. Using quantitative
      PCR, (13)C-labelled bacterial ribosomal RNA and DNA was detected after 21 and 32
      days of incubation with [U-(13)C]acetate respectively. In the heavy fractions of
      the (13)C treatment, terminal restriction fragments (T-RFs) of 140, 120 and 171
      bp length predominated. Cloning and sequencing of 16S rRNA showed that these T
      RFs were affiliated with the bacterial genera Thermacetogenium and
      Symbiobacterium and with members of the Thermoanaerobacteriaceae. Similar
      experiments targeting archaeal RNA and DNA showed that Methanocellales were the
      dominant methanogens being consistent with the operation of syntrophic bacterial
      acetate oxidation coupled to hydrogenotrophic methanogenesis. After 17 days,
      however, Methanosarcinacea increasingly contributed to the synthesis of rRNA from
      [U-(13)C]acetate indicating that acetoclastic methanogens were also active in
      methanogenic Italian rice field soil under thermal conditions.

PMID- 21966925
TI  - High symbiont diversity in the bone-eating worm Osedax mucofloris from shallow
      whale-falls in the North Atlantic.
AB  - Osedax worms are whale-fall specialists that infiltrate whale bones with their
      root tissues. These are filled with endosymbiotic bacteria hypothesized to
      provide their hosts with nutrition by extracting organic compounds from the whale
      bones. We investigated the diversity and distribution of symbiotic bacteria in
      Osedax mucofloris from shallow-water whale-falls in the North Atlantic using
      comparative 16S rRNA sequence analysis and fluorescence in situ hybridization
      (FISH). We observed a higher diversity of endosymbionts than previously described
      from other Osedax species. Endosymbiont sequences fell into eight
      phylogenetically distinct clusters (with 91.4-98.9% similarity between clusters),
      and considerable microdiversity within clusters (99.5-99.7% similarity) was
      observed. Statistical tests revealed a highly significant effect of the host
      individual on endosymbiont diversity and distribution, with 68% of the
      variability between clusters and 40% of the variability within clusters explained
      by this effect. FISH analyses showed that most host individuals were dominated by
      endosymbionts from a single cluster, with endosymbionts from less abundant
      clusters generally confined to peripheral root tissues. The observed diversity
      and distribution patterns indicate that the endosymbionts are transmitted
      horizontally from the environment with repeated infection events occurring as the
      host root tissues grow into the whale bones.

PMID- 21966926
TI  - First description of giant Archaea (Thaumarchaeota) associated with putative
      bacterial ectosymbionts in a sulfidic marine habitat.
AB  - Archaea may be involved in global energy cycles, and are known for their ability
      to interact with eukaryotic species (sponges, corals and ascidians) or as
      archaeal-bacterial consortia. The recently proposed phylum Thaumarchaeota may
      represent the deepest branching lineage in the archaeal phylogeny emerging before
      the divergence between Euryarchaeota and Crenarchaeota. Here we report the first
      characterization of two marine thaumarchaeal species from shallow waters that
      consist of multiple giant cells. One species is coated with sulfur-oxidizing
      gamma-Proteobacteria. These new uncultured thaumarchaeal species are able to live
      in the sulfide-rich environments of a tropical mangrove swamp, either on living
      tissues such as roots or on various kinds of materials such as stones, sunken
      woods, etc. These archaea and archaea/bacteria associations have been studied
      using light microscopy, transmission electron microscopy and scanning electron
      microscopy. Species identification of archaeons and the putative bacterial
      symbiont have been assessed by 16S small subunit ribosomal RNA analysis. The
      sulfur-oxidizing ability of the bacteria has been assessed by genetic
      investigation on alpha-subunit of the adenosine-5'-phosphosulfate
      reductase/oxidase's (AprA). Species identifications have been confirmed by
      fluorescence in situ hybridization using specific probes designed in this study.
      In this article, we describe two new giant archaeal species that form the biggest
      archaeal filaments ever observed. One of these species is covered by a specific
      biofilm of sulfur-oxidizing gamma-Proteobacteria. This study highlights an
      unexpected morphological and genetic diversity of the phylum Thaumarchaeota.

PMID- 21966927
TI  - Poor impulse control predicts inelastic demand for nicotine but not alcohol in
      rats.
AB  - Tobacco and alcohol dependence are characterized by continued use despite
      deleterious health, social and occupational consequences, implying that addicted
      individuals pay a high price for their use. In behavioral economic terms, such
      persistent consumption despite increased costs can be conceptualized as inelastic
      demand. Recent animal studies demonstrated that high-impulsive individuals are
      more willing to work for nicotine or cocaine infusions than their low-impulsive
      counterparts, indicating that this trait might be causally related to inelastic
      drug demand. By employing progressive ratio schedules of reinforcement combined
      with a behavioral economics approach of analysis, we determined whether trait
      impulsivity is associated with an insensitivity of nicotine or alcohol
      consumption to price increments. Rats were trained on a delayed discounting task,
      measuring impulsive choice. Hereafter, high- and low-impulsive rats were selected
      and trained to nose poke for intravenous nicotine or oral alcohol. Upon stable
      self-administration on a continuous reinforcement schedule, the price (i.e.
      response requirement) was increased. Demand curves, depicting the relationship
      between price and consumption, were produced using Hursh's exponential demand
      equation. Similar to human observations, nicotine and alcohol consumption in rats
      fitted this equation, thereby demonstrating the validity of our model. Moreover,
      high-impulsive rats displayed inelastic nicotine demand, as their nicotine
      consumption was less sensitive to price increments as compared with that in low
      impulsive rats. Impulsive choice was not related to differences in alcohol demand
      elasticity. Our model seems well suited for studying nicotine and alcohol demand
      in rats and, as such, might contribute to our understanding of tobacco and
      alcohol dependence.

PMID- 21966928
TI  - Quantum chemical study of redox-switchable second-order nonlinear optical
      responses of D-pi-A system BNbpy and metal Pt(II) chelate complex.
AB  - A second-order nonlinear optical (NLO) molecular switching with redox has been
      investigated in the present paper. The static first hyperpolarizabilities of 5
      (BMes(2))-5'-(NPh(2))-2,2'-bipyridine (BNbpy) containing three-coordinate
      organoboron, Pt(II) chelate complex Pt(BNbpy)Ph(2), and their reduced forms have
      been calculated by density functional theory (DFT) combined with the analytic
      derivatives method. There is an enhancement of static first hyperpolarizabilities
      in the reduced form according to the calculations. That is, the beta(vec) value
      of one-electron-reduced form is ~7 times as large as that of neutral form BNbpy;
      the beta(vec) values of one- and two-electron-reduced forms are ~3 and ~4 times
      as large as that of neutral form Pt(BNbpy)Ph(2), respectively. In particular, the
      beta(vec) value of two-electron-reduced form (3)Pt(BNbpy)Ph(2)(2-) is 1349 * 10(
      30) esu, ~286 times larger than its neutral form. Moreover, the component beta(z)
      value of the metal chelate complex Pt(BNbpy)Ph(2) is 25 * 10(-30) esu, which is
      ~14 times as large as that of ligand BNbpy; the corresponding F(-)/CN(-)
      compounds show a decrease in beta(x) values compared with the case of the ligand
      and Pt(II) complex. Analyses of geometries, density of states (DOS), and time
      dependent DFT (TDDFT) calculations reveal that the one-electron reduction
      promotes the molecular conjugation in the x-axis and intensifies the interaction
      between the metal Pt(II) and ligand and then results in an enhancement of the
      static first hyperpolarizability, whereas the binding of F(-)/CN(-) to the B atom
      turns off the p(pi)-pi* conjugation and has no effect on the conjugation of
      bipyridine, which leads to a decreasing beta value in the x-axis.

PMID- 21966930
TI  - Eldercare demands, mental health, and work performance: the moderating role of
      satisfaction with eldercare tasks.
AB  - Due to demographic changes, a growing number of employees provide in-home care to
      an elderly family member. Previous research suggested a negative relationship
      between employees' eldercare demands and their work performance. However, the
      empirical nature of this relationship and its boundary conditions and mediating
      mechanisms have been neglected. The goal of this multisource study was to examine
      a mediated-moderation model of eldercare demands, mental health, and work
      performance. Drawing on the theory of conservation of resources (Hobfoll, 1989),
      it was expected that employees' satisfaction with eldercare tasks would buffer
      the negative relationship between eldercare demands and work performance, and
      that mental health would mediate this moderating effect. Data were collected from
      165 employees providing in-home eldercare, as well as from one colleague and one
      family member of each employee. Results of mediated-moderation analyses supported
      the hypothesized model. The findings suggest that interventions that aim to
      increase employees' satisfaction with eldercare tasks may help protect employees
      from the negative effects of high eldercare demands on mental health and,
      subsequently, on work performance.

PMID- 21966929
TI  - Hepatogenic differentiation of mesenchymal stem cells in a rat model of
      thioacetamide-induced liver cirrhosis.
AB  - Implantation of bone-marrow-derived MSCs (mesenchymal stem cells) has emerged as
      a potential treatment modality for liver failure, but in vivo differentiation of
      MSCs into functioning hepatocytes and its therapeutic effects have not yet been
      determined. We investigated MSC differentiation process in a rat model of TAA
      (thioacetamide)-induced liver cirrhosis. Male Sprague-Dawley rats were
      administered 0.04% TAA-containing water for 8 weeks, MSCs were injected into the
      spleen for transsplenic migration into the liver, and liver tissues were examined
      over 3 weeks. Ingestion of TAA for 8 weeks induced micronodular liver cirrhosis
      in 93% of rats. Injected MSCs were diffusely engrafted in the liver parenchyma,
      differentiated into CK19 (cytokeratin 19)- and thy1-positive oval cells and later
      into albumin-producing hepatocyte-like cells. MSC engraftment rate per slice was
      measured as 1.0-1.6%. MSC injection resulted in apoptosis of hepatic stellate
      cells and resultant resolution of fibrosis, but did not cause apoptosis of
      hepatocytes. Injection of MSCs treated with HGF (hepatocyte growth factor) in
      vitro for 2 weeks, which became CD90-negative and CK18-positive, resulted in
      chronological advancement of hepatogenic cellular differentiation by 2 weeks and
      decrease in anti-fibrotic activity. Early differentiation of MSCs to progenitor
      oval cells and hepatocytes results in various therapeutic effects, including
      repair of damaged hepatocytes, intracellular glycogen restoration and resolution
      of fibrosis. Thus, these results support that the in vivo hepatogenic
      differentiation of MSCs is related to the beneficial effects of MSCs rather than
      the differentiated hepatocytes themselves.

PMID- 21966931
TI  - Moderators of informant agreement in the assessment of adolescent
      psychopathology: extension to a forensic sample.
AB  - A well-documented finding in developmental psychopathology research is that
      different informants often provide discrepant ratings of a youth's internalizing
      and externalizing problems. The current study examines youth- and parent-based
      moderators (i.e., youth age, gender, and IQ; type of psychopathology; offense
      category; psychopathic traits; parental education, income, and stress) of
      informant discrepancies in a sample of young offenders and compares the utility
      of youth and caregiver reports against relevant clinical outcomes. Results
      indicate that gender moderated the discrepancy between informant reports of
      somatic complaints, while parenting stress moderated the discrepancies across
      reports of internalizing and externalizing psychopathology. Variables unique to
      the forensic context (e.g., offense category) were found to moderate cross
      informant discrepancies in reports of internalizing and externalizing
      psychopathology. Further, youth self-reports of internalizing symptoms predicted
      a clinician-generated diagnosis of a mood disorder, while caregiver reports of
      aggressive behaviors predicted the presence of an externalizing diagnosis.
      Results highlight the importance of assessing informant agreement in the context
      of forensic assessment and raise questions surrounding the optimal use of
      informant data in this setting.

PMID- 21966932
TI  - Psychometric evaluation of the Fear of Positive Evaluation Scale in patients with
      social anxiety disorder.
AB  - The Fear of Positive Evaluation Scale (FPES; J. W. Weeks, R. G. Heimberg, & T. L.
      Rodebaugh, 2008) was designed to assess fear of positive evaluation, a proposed
      cognitive component of social anxiety. Although previous findings on the
      psychometric properties of the FPES have been highly encouraging, only 1 previous
      study has examined the psychometric profile of the FPES in a sample of patients
      with social anxiety disorder (T. A. Fergus et al., 2009). The primary purpose of
      the present study was to conduct a large multisite examination of the
      psychometric profile of the FPES among patients with a principal diagnosis of
      social anxiety disorder (n = 226; generalized subtype = 97.8%). Responses of
      nonanxious control participants (n = 42) were also examined. The factorial
      validity, internal consistency, test-retest reliability, construct validity, and
      treatment sensitivity of the FPES were strongly supported by our findings.
      Furthermore, an FPES cutoff score was identified for distinguishing levels of
      fear of positive evaluation characteristic of patients with social anxiety
      disorder from those characteristic of the control group. Results provide
      additional support for the psychometric properties of the FPES in clinical
      samples.

PMID- 21966933
TI  - Determining the number of factors to retain in an exploratory factor analysis
      using comparison data of known factorial structure.
AB  - Exploratory factor analysis (EFA) is used routinely in the development and
      validation of assessment instruments. One of the most significant challenges when
      one is performing EFA is determining how many factors to retain. Parallel
      analysis (PA) is an effective stopping rule that compares the eigenvalues of
      randomly generated data with those for the actual data. PA takes into account
      sampling error, and at present it is widely considered the best available method.
      We introduce a variant of PA that goes even further by reproducing the observed
      correlation matrix rather than generating random data. Comparison data (CD) with
      known factorial structure are first generated using 1 factor, and then the number
      of factors is increased until the reproduction of the observed eigenvalues fails
      to improve significantly. We evaluated the performance of PA, CD with known
      factorial structure, and 7 other techniques in a simulation study spanning a wide
      range of challenging data conditions. In terms of accuracy and robustness across
      data conditions, the CD technique outperformed all other methods, including a
      nontrivial superiority to PA. We provide program code to implement the CD
      technique, which requires no more specialized knowledge or skills than performing
      PA.

PMID- 21966934
TI  - The measurement of executive function at age 5: psychometric properties and
      relationship to academic achievement.
AB  - This study examined the psychometric properties and criterion validity of a newly
      developed battery of executive function (EF) tasks for use in early childhood.
      The battery was included in the Family Life Project (FLP), a prospective
      longitudinal study of families who were oversampled from low-income and African
      American families at the birth of a new child (N = 1,292). Ninety-nine percent (N
      = 1,036) of children who participated in the age 5 home visit completed 1 or more
      (M = 5.8, Mdn = 6) of the 6 EF tasks. Results indicated that tasks worked equally
      well for children residing in low-income and not low-income homes, that task
      scores were most informative about the ability level of children in the low
      average range, that performance on EF tasks was best characterized by a single
      factor, and that individual differences on the EF battery were strongly related
      to a latent variable measuring overall academic achievement, as well as to
      individual standardized tests that measured phonological awareness, letter-word
      identification, and early math skills.

PMID- 21966935
TI  - Prenatal programming of renal salt wasting resets postnatal salt appetite, which
      drives food intake in the rat.
AB  - Sodium retention has been proposed as the cause of hypertension in the LP rat
      (offspring exposed to a maternal low-protein diet in utero) model of
      developmental programming because of increased renal NKCC2 (Na+/K+/2Cl- co
      transporter 2) expression. However, we have shown that LP rats excrete more
      rather than less sodium than controls, leading us to hypothesize that LP rats
      ingest more salt in order to maintain sodium balance. Rats were fed on either a
      9% (low) or 18% (control) protein diet during pregnancy; male and female
      offspring were studied at 4 weeks of age. LP rats of both sexes held in
      metabolism cages excreted more sodium and urine than controls. When given water
      to drink, LP rats drank more and ate more food than controls, hence sodium intake
      matched excretion. However, when given a choice between saline and water to
      drink, the total volume of fluid ingested by LP rats fell to control levels, but
      the volume of saline taken was significantly larger [3.8+/-0.1 compared with
      8.8+/-1.3 ml/24 h per 100 g of body weight in control and LP rats respectively;
      P<0.001]. Interestingly food intake also fell to control levels. Total body
      sodium content and ECF (extracellular fluid) volumes were greater in LP rats.
      These results show that prenatal programming of renal sodium wasting leads to a
      compensatory increase in salt appetite in LP rats. We speculate that the need to
      maintain salt homoeostasis following malnutrition in utero stimulates greater
      food intake, leading to accelerated growth and raised BP (blood pressure).

PMID- 21966936
TI  - Not all lubricin isoforms are substituted with a glycosaminoglycan chain.
AB  - Lubricin, also referred to as superficial zone protein, has been reported to be a
      proteoglycan. However, the structure of its glycosaminoglycan chain has not been
      well characterized, and this study was undertaken to investigate the structure of
      the glycosaminoglycan chain that decorated lubricin in human synovial fluid to
      provide insight into its biological role. Lubricin was detected as a major band
      at approximately 360 kDa which co-migrated in sodium dodecyl sulfate
      polyacrylamide gel electrophoresis with a chondroitin sulfate (CS)-containing
      proteoglycan that was detected by both monoclonal antibodies (MAb) 2-B-6 and MAb
      3-B-3 after chondroitinase ABC treatment and keratan sulfate (KS) that was
      detected by MAb 5-D-4. Further analysis of lubricin-containing fractions that
      eluted from an anion exchange column indicated that the major population of
      lubricin could be separated from the CS and KS stubs which indicated that this
      fraction of lubricin was not decorated with glycosaminoglycan chain and was the
      glycoprotein form of lubricin. Lubricin present in fractions that also contained
      CS was found to be decorated with CS structures which were reactive with MAb 3-B
      3 after chondroitinase ABC digestion using a sandwich enzyme-linked immunosorbent
      assay approach. Aggrecan was not found to form complexes with lubricin in
      synovial fluid which confirmed that the MAb 3-B-3 CS and MAb 5-D-4 KS structures
      decorated lubricin. These data demonstrate that lubricin present in human
      synovial fluid was a heterogeneous population with both glycoprotein and
      proteoglycan forms.

PMID- 21966937
TI  - Nutrient patterns and risk of esophageal squamous cell carcinoma: a case-control
      study.
AB  - Although Iran is a high-risk country for esophageal squamous cell carcinoma
      (ESCC), the contribution of overall nutrient intakes to this high incidence rate
      is not yet clear. The aim of this study was to examine the association between
      nutrient patterns and risk of ESCC in Iran. Forty-seven patients with ESCC and 96
      frequency-matched hospital controls underwent private interviews, and dietary
      habits were collected using a validated food-frequency questionnaire. Factor
      analysis was conducted and two major nutrient patterns were retained; factor 1
      (high in pantothenic acid, vitamin C, potassium, vitamin B(6), magnesium, folate,
      thiamin, copper, carbohydrate, vitamin K, niacin, alpha-tocopherol, zinc, total
      fiber, fluoride, and polyunsaturated fatty acids) and factor 2 (high in saturated
      fatty acid, biotin, selenium, monounsaturated fatty acids, riboflavin, sodium,
      fat, cholesterol, calcium, phosphorus, protein, iron, vitamin E, manganese,
      vitamin D, and vitamin B(12)). Factor 2 was inversely associated with ESCC (OR =
      0.06, 95% CI: 0.01-0.28; P = 0.008), whereas no significant association was found
      for factor 1 (OR = 0.45, 95% CI: 0.11-1.82). The results of the present study
      suggested a possible role for a nutrient pattern similar to factor 2 in reducing
      the risk of ESCC.

PMID- 21966941
TI  - MWA combined with TACE as a combined therapy for unresectable large-sized
      hepotocellular carcinoma.
AB  - PURPOSE: To evaluate the efficacy and safety of microwave ablation combined with
      transcatheter arterial chemoembolization for unresectable large-sized
      hepotocellular carcinoma. MATERIALS AND METHODS: Institutional review board
      approval and informed consent were obtained. Between May 2004 and December 2006,
      34 consecutive patients with large unresectable hepatocellular carcinoma (>5 cm)
      were alternately enrolled in one of two treatment groups: group 1 (n = 18), in
      which TACE was performed alone, and group 2 (n = 16), in which percutaneous
      ablation of HCC with microwave ablation was performed 2-4 weeks after TACE. All
      patients were followed up for 2-28 months to observe long-term therapeutic
      effects and complications in both groups. Tumor reduction rates, median survival
      time, and cumulative survival rates in both groups were calculated by using the
      unpaired Student t test and Kaplan-Meier method. RESULTS: Follow-up images showed
      reduction in tumor size was seen in 21 patients (61.7%; 7/18 in group 1, 14/16 in
      group 2), survival rates were better in group 2 than in group 1 (P = 0.003),
      during the median follow-up of 8 months, 10 patients (62.5%) remained alive in
      group 2, whereas 6 patients (33.3%) remained alive in group 1, the mean survival
      times were 6.13 months +/- 0.83 in group 1 and 11.61 months +/- 1.59 in group 2.
      CONCLUSION: MWA combined with transcatheter arterial chemoembolization appears to
      be an effective and promising approach for the treatment of large-sized
      unresectable hepotocellular carcinoma. However, large-scale randomized clinical
      trials are needed to determine the future role of this treatment.

PMID- 21966942
TI  - Fluoxetine inhibits inflammatory response and bone loss in a rat model of
      ligature-induced periodontitis.
AB  - BACKGROUND: Fluoxetine, a selective serotonin reuptake inhibitor, has been found
      recently to possess anti-inflammatory properties. The present study investigates
      the effects of fluoxetine on inflammatory tissue destruction in a rat model of
      ligature-induced periodontal disease. METHODS: Thirty male Wistar rats were
      randomly assigned into three groups (n = 10 animals per group): 1) control rats
      (without ligature); 2) rats with ligature + placebo (saline; oral gavage); and 3)
      rats with ligature + fluoxetine (20 mg/kg/day in saline; oral gavage). Histologic
      analyses were performed on the furcation region and mesial aspect of mandibular
      first molars of rats sacrificed at 15 days after ligature-induced periodontal
      disease. Reverse transcription-polymerase chain reaction and zymography were
      performed to analyze the mRNA expression of interleukin (IL)-1beta,
      cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-9 and inducible nitric
      oxide synthase and the MMP-9 activity, respectively, in gingival tissues samples.
      RESULTS: Compared to the ligature + placebo group, alveolar bone loss was reduced
      in the fluoxetine group (P <0.05), and the amount of collagen fibers in the
      gingival tissue was maintained. Moreover, in gingival tissue sampled 3 days after
      ligature attachment, fluoxetine administration reduced IL-1beta and COX-2 mRNA
      expression. Fluoxetine downregulated MMP-9 activity, without affecting MMP-9 mRNA
      expression induced by ligature, compared to the ligature + placebo group (P
      <0.05). These data suggest that fluoxetine suppressed proinflammatory responses,
      as well as proteolytic enzyme activity, induced by ligature. CONCLUSION: In the
      present study, fluoxetine suppresses the inflammatory response and protects
      against periodontal bone resorption and destruction of collagen fibers,
      suggesting that fluoxetine can constitute a promising therapeutic approach for
      periodontal diseases.

PMID- 21966943
TI  - Patterns of diabetic periodontal wound repair: a study using micro-computed
      tomography and immunohistochemistry.
AB  - BACKGROUND: Diabetes is known to impair wound healing and deteriorate the
      periodontal condition. There is limited information about the patterns and events
      associated with periodontal wound repair. In this study, we evaluate the dynamics
      of periodontal wound repair using micro-computed tomography (microCT) and
      immunohistochemistry. METHODS: Thirty-six male rats were used, and diabetes was
      induced by streptozotocin. The maxillary first molars were extracted, and a tooth
      associated osseous defect was created in the extraction area. Animals were
      sacrificed after 7, 14, and 21 days. Volumetry and distribution of bone
      trabeculae were evaluated by microCT imaging. The patterns of healing and
      collagen alignment were evaluated by histology. Advanced glycation end-product
      (AGE) deposition and expression of the receptor for AGEs (RAGE), tartrate
      resistant acid phosphatase, and proliferating cell nuclear antigen were evaluated
      by histochemical and immunohistochemical staining. RESULTS: Diabetic animals
      demonstrated a significantly reduced bone volume and trabecular number as well as
      thinner trabeculae and more trabecular separation in osseous defects. The early
      stage was characterized by significantly reduced cellular proliferation and
      prolonged active inflammation without evident bone resorption, whereas delayed
      recovery of collagen realignment, matrix deposition, and bone turnover was noted
      in later stages. Although AGEs and RAGE were present during healing in diabetes
      and controls, a stronger and more persistent level of expression was observed in
      the group with diabetes CONCLUSIONS: Diabetes significantly delayed osseous
      defect healing by augmenting inflammation, impairing proliferation, and delaying
      bone resorption. The AGE-RAGE axis can be activated under metabolic disturbance
      and inflammation.

PMID- 21966944
TI  - Association of serum and crevicular visfatin levels in periodontal health and
      disease with type 2 diabetes mellitus.
AB  - BACKGROUND: Levels of visfatin in serum and gingival crevicular fluid (GCF) were
      explored in patients with periodontal health, periodontal disease with and
      without type 2 diabetes mellitus (t2 DM) and were found to be elevated with
      periodontal disease, and were correlated with periodontal clinical parameters. DM
      and chronic periodontitis (CP) are associated with each other. Adipokines,
      specifically visfatin, are secreted from adipocytes and are thought to cause
      insulin resistance. The purpose of this study is to determine the presence of
      visfatin in serum and GCF in t2 DM among individuals with CP and to find an
      association, if any. METHODS: Thirty individuals (15 males and 15 females) were
      selected based on their clinical parameters into three groups: group 1 (10
      healthy), group 2 (10 well-controlled t2 DM among individuals with CP), and group
      3 (10 individuals with CP and without diabetes). Serum and GCF samples were
      collected to estimate the levels of visfatin using enzyme linked immunosorbent
      assay. RESULTS: The mean visfatin concentration increased in both serum and GCF
      in individuals with t2 DM with CP. Also, it was observed that visfatin in both
      serum and GCF correlated positively with all the periodontal parameters.
      CONCLUSIONS: All the samples in each group tested positive for visfatin assay.
      Serum and GCF visfatin concentration in both t2 DM with CP and individuals with
      CP and without diabetes correlated positively with all the clinical parameters.
      Additional large-scale longitudinal studies should be performed to confirm
      positive correlations.

PMID- 21966945
TI  - Increased inflammatory markers are associated with obesity and not with target
      organ damage in newly diagnosed untreated essential hypertensive patients.
AB  - The aim of this study was to investigate whether inflammatory markers are
      associated with hypertensive end organ damage or obesity in patients with
      hypertension. Seventy newly diagnosed essential hypertensive patients (29 men and
      41 women aged 49.6 +/- 9.5 y) and 25 age-sex-matched normotensive subjects (12
      men and 13 women aged 45.8 +/- 7.3 y) were asked about their family history of
      hypertension and smoking habits, and body mass index (BMI) was recorded and blood
      samples were taken to measure fibrinogen, C-reactive protein (CRP), and
      homocysteine levels. In hypertensive patients, creatinine clearance, urinary
      albumin extraction, and left ventricular mass index were determined. Hypertensive
      patients had significantly higher BMIs and inflammatory markers when compared
      with normotensive healthy controls. The CRP was positively associated with BMI (P
      < .05), diastolic blood pressure (P < .05), fibrinogen (P < .01), urinary albumin
      extraction (P < .01), and left ventricular mass index (P < .05). The BMI and
      serum fibrinogen level were independently associated with CRP. The effect of
      inflammation on the development of hypertensive end organ damage may be
      associated with obesity, so that control of obesity may eliminate the
      inflammatory state in hypertensive patients and also hypertensive end organ
      damage.

PMID- 21966946
TI  - Oral acanthosis nigricans in chronic hepatitis B with a 21-year follow up.
AB  - Acanthosis nigricans is a rare mucocutaneous disorder of unknown etiology that
      manifests as hyperpigmented velvety plaques, most often on intertriginous areas
      such as the neck and axillae as well as on mucosal sites such as the oral cavity.
      The disorder presents either as a paraneoplastic manifestation of an underlying
      malignancy, especially gastrointestinal adenocarcinomas or in association with
      obesity, administration of drugs or endocrinopathies, most commonly insulin
      resistant diabetes mellitus. In the present article, a case of acanthosis
      nigricans with oral and cutaneous manifestations in a male patient with chronic
      hepatitis B infection is described. To the best of our knowledge, this is the
      first case of benign oral acanthosis nigricans associated with chronic hepatitis
      B.

PMID- 21966947
TI  - Treatment of seborrhoeic dermatitis of the scalp with a topical solution of urea,
      lactic acid, and propylene glycol (K301): results of two double-blind,
      randomised, placebo-controlled studies.
AB  - Alternative treatments for seborrhoeic dermatitis are needed because of the
      increasing risk of anti-fungal resistance to existing therapies. To investigate
      the efficacy, safety and tolerability of topical scalp treatment with K301
      solution. Two multi-centre, randomised, double-blind studies were conducted.
      Study I: 4 weeks of once-daily treatment with either one form of K301 (a or b) or
      placebo, followed by 4 weeks of maintenance treatment three times-per-week. Study
      II: 4 weeks of K301 (a) or placebo once-daily. Study I: 98 patients enrolled
      (K301a + b, n = 51; placebo, n = 47) and 83 completed; 201 entered Study II
      (K301a, n = 136; placebo, n = 65) and 195 completed. Erythema and desquamation
      sum score at 4 weeks, mean (SD) values were 2.4 (2.0) for K301a + b and 3.2 (2.2)
      for placebo in Study I (P = 0.025) and 2.5 (1.9) for K301a and 3.2 (1.8) for
      placebo in Study II (not significant). In both studies, 4-week desquamation
      scores were significantly improved for K301 vs. placebo (P < 0.05). Both studies
      showed significant improvements in symptomatic investigator and patient
      assessments for K301 over placebo after 4 weeks (P < 0.05). Treatment-related
      adverse events were generally mild and included some smarting or burning upon
      application. The K301 was well tolerated and associated with clinically
      meaningful improvements in seborrhoeic dermatitis endpoints.

PMID- 21966949
TI  - Safe and successful treatment of acne vulgaris with isotretinoin in a patient
      with chronic granulomatous disease.
AB  - Isotretinoin for acne vulgaris in the setting of chronic granulomatous disease
      (CGD) is a controversial therapeutic option. In this inherited immunodeficiency,
      inefficient tissue responses to bacteria and fungi lead to chronic and recurrent
      infections. Isotretinoin is known to be associated with several mucocutaneous
      side effects that could worsen the immune response in individuals with CGD. We
      report the fourth published case of acne vulgaris treated with isotretinoin in an
      individual with CGD, with a safe and successful outcome.

PMID- 21966948
TI  - Gas chromatographic analysis with chiral cyclodextrin phases reveals the
      enantioselective formation of hydroxylated polychlorinated biphenyls by rat liver
      microsomes.
AB  - Chiral PCB congeners are major components of PCB mixtures and undergo
      enantioselective biotransformation to hydroxylated (OH-)PCBs by cytochrome P450
      enzymes. While it is known that biotransformation results in an enantiomeric
      enrichment of the parent PCB, it is currently unknown if OH-PCBs are formed
      enantioselectively. The present study screened seven commercial capillary gas
      chromatography columns containing modified beta- or gamma-cyclodextrins for their
      potential to separate the atropisomers of methylated derivatives of OH-PCB. The
      atropisomers of 3-, 4- and 5-methoxy derivatives were at least partially
      separated on one or more columns. A subsequent biotransformation study was
      performed with rat liver microsomes to assess if hydroxylated metabolites are
      formed enantioselectively from PCBs 91, 95, 132, and 149. The OH-PCBs were
      extracted from the microsomal incubations, derivatized with diazomethane and
      analyzed as the respective methoxylated (MeO-)PCB derivatives using selected
      columns. The 5-hydroxylated metabolites of PCBs 91, 95, 132, and 149 were the
      major metabolites, which is consistent with PCB's biotransformation by cytochrome
      P450 2B enzymes. All 5-hydroxylated metabolites displayed a clear, congener
      specific enantiomeric enrichment. Overall, this study demonstrates for the first
      time that chiral PCBs, such as PCB 91, 95, 132, and 149, are enantioselectively
      metabolized to OH-PCBs by cytochrome P450 enzymes.

PMID- 21966951
TI  - A facile synthesis of substituted 2-alkylquinolines through [3+3] annulation
      between 3-ethoxycyclobutanones and aromatic amines at room temperature.
AB  - An efficient single-step approach toward the synthesis of 2-alkylquinolines is
      described. Through a Lewis acid mediated [3+3] annulation reaction between 3
      ethoxycyclobutanones and aromatic amines, a variety of multisubstituted 2
      alkylquinoline derivatives were prepared regioselectively at room temperature.

PMID- 21966950
TI  - Targeting zymogen activation to control the matriptase-prostasin proteolytic
      cascade.
AB  - Membrane-associated serine protease matriptase has been implicated in human
      diseases and might be a drug target. In the present study, a novel class of
      matriptase inhibitors targeting zymogen activation is developed by a combination
      of the screening of compound library using a cell-based matriptase activation
      assay and a computer-aided search of commercially available analogues of a
      selected compound. Four structurally related compounds are identified that can
      inhibit matriptase activation with IC(50) at low micromolar concentration in both
      intact-cell and cell-free systems, suggesting that these inhibitors target the
      matriptase autoactivation machinery rather than the intracellular signaling
      pathways. These activation inhibitors can also inhibit prostasin activation, a
      downstream event that occurs in lockstep with matriptase activation. In contrast,
      the matriptase catalytic inhibitor CVS-3983 at a concentration 300-fold higher
      than its K(i) fails to inhibit activation of either protease. Our results suggest
      that inhibiting matriptase activation is an efficient way to control matriptase
      function.

PMID- 21966952
TI  - Association of systemic psoriasis therapies and incidence of myocardial
      infarction: reply from authors.

PMID- 21966953
TI  - Rapamycin causes upregulation of autophagy and impairs islets function both in
      vitro and in vivo.
AB  - Autophagy is a lysosomal degradation process of redundant or faulty cell
      components in normal cells. However, certain diseases are associated with
      dysfunctional autophagy. Rapamycin, a major immunosuppressant used in islet
      transplantation, is an inhibitor of mammalian target of rapamycin and is known to
      cause induction of autophagy. The objective of this study was to evaluate the in
      vitro and in vivo effects of rapamycin on pancreatic beta cells. Rapamycin
      induced upregulation of autophagy in both cultured isolated islets and pancreatic
      beta cells of green fluorescent protein-microtubule-associated protein 1 light
      chain 3 transgenic mice. Rapamycin reduced the viability of isolated beta cells
      and down-regulated their insulin function, both in vitro and in vivo. In
      addition, rapamycin increased the percentages of apoptotic beta cells and dead
      cells in both isolated and in vivo intact islets. Treatment with 3-methyladenine,
      an inhibitor of autophagy, abrogated the effects of rapamycin and restored beta
      cell function in both in vitro experiments and animal experiments. We conclude
      that rapamycin-induced islet dysfunction is mediated through upregulation of
      autophagy, with associated downregulation of insulin production and apoptosis of
      beta cells. The results also showed that the use of an autophagy inhibitor
      abrogated these effects and promoted islet function and survival. The study
      findings suggest that targeting the autophagy pathway could be beneficial in
      promoting islet graft survival after transplantation.

PMID- 21966955
TI  - Regression formulas for density functional theory calculated 1H and 13C NMR
      chemical shifts in toluene-d8.
AB  - This study aimed at investigating the performance of a series of basis sets,
      density functional theory (DFT) functionals, and the IEF-PCM solvation model in
      the accurate calculation of (1)H and (13)C NMR chemical shifts in toluene-d(8).
      We demonstrated that, on a test set of 37 organic species with various functional
      moieties, linear scaling significantly improved the calculated shifts and was
      necessary to obtain more accurate results. Inclusion of a solvation model
      produced larger deviations from the experimental data as compared to the gas
      phase calculations. Moreover, we did not find any evidence that very large basis
      sets were necessary to reproduce the experimental NMR data. Ultimately, we
      recommend the use of the BMK functional. For the (1)H shifts the use of the 6
      311G(d) basis set gave linearly scaled mean unsigned (MU) and root-mean-square
      (rms) errors of 0.15 ppm and 0.21 ppm, respectively. For the calculation of the
      (13)C chemical shifts the 6-31G(d) basis set produced MUE of 1.82 ppm and RMSE of
      3.29 ppm.

PMID- 21966954
TI  - A hitchhikers guide to the Galapagos: co-phylogeography of Galapagos mockingbirds
      and their parasites.
AB  - BACKGROUND: Parasites are evolutionary hitchhikers whose phylogenies often track
      the evolutionary history of their hosts. Incongruence in the evolutionary history
      of closely associated lineages can be explained through a variety of possible
      events including host switching and host independent speciation. However, in
      recently diverged lineages stochastic population processes, such as retention of
      ancestral polymorphism or secondary contact, can also explain discordant
      genealogies, even in fully co-speciating taxa. The relatively simple
      biogeographic arrangement of the Galapagos archipelago, compared with mainland
      biomes, provides a framework to identify stochastic and evolutionary informative
      components of genealogic data in these recently diverged organisms. RESULTS:
      Mitochondrial DNA sequences were obtained for four species of Galapagos
      mockingbirds and three sympatric species of ectoparasites--two louse and one mite
      species. These data were complemented with nuclear EF1alpha sequences in selected
      samples of parasites and with information from microsatellite loci in the
      mockingbirds. Mitochondrial sequence data revealed differences in population
      genetic diversity between all taxa and varying degrees of topological congruence
      between host and parasite lineages. A very low level of genetic variability and
      lack of congruence was found in one of the louse parasites, which was excluded
      from subsequent joint analysis of mitochondrial data. The reconciled multi
      species tree obtained from the analysis is congruent with both the nuclear data
      and the geological history of the islands. CONCLUSIONS: The gene genealogies of
      Galapagos mockingbirds and two of their ectoparasites show strong phylogeographic
      correlations, with instances of incongruence mostly explained by ancestral
      genetic polymorphism. A third parasite genealogy shows low levels of genetic
      diversity and little evidence of co-phylogeny with their hosts. These differences
      can mostly be explained by variation in life-history characteristics, primarily
      host specificity and dispersal capabilities. We show that pooling genetic data
      from organisms living in close ecological association reveals a more accurate
      phylogeographic history for these taxa. Our results have implications for the
      conservation and taxonomy of Galapagos mockingbirds and their parasites.

PMID- 21966956
TI  - HbA(1c) in adults without known diabetes from southern Europe. Impact of the new
      diagnostic criteria in clinical practice.
AB  - AIMS: To analyse the differences in the prevalence of diabetes and dysglycaemia
      using fasting plasma glucose and HbA(1c) criteria. METHODS: Analytical cross
      sectional study undertaken in a random sample of 2144 individuals (age 18-80
      years) without known diabetes from the primary care setting in Malaga (Spain).
      Dysglycaemia was defined as fasting plasma glucose 5.6-6.9 mmol/l or HbA(1c) 39
      46 mmol/mol (5.7-6.4%) and diabetes as fasting plasma glucose >= 7.0 mmol/l or
      HbA(1c)>= 48 mmol/mol (>= 6.5%). RESULTS: The proportion of subjects who were
      normoglycaemic was significantly higher using fasting plasma glucose than HbA(1c)
      (83.5 vs. 65%) (P < 0.0001). Compared with fasting plasma glucose, HbA(1c)
      detects more cases of dysglycaemia (32 vs. 14.8%) (P < 0.0001) and diabetes (3
      vs. 1.7%) (P < 0.0001). CONCLUSIONS: In our environment, using HbA(1c) for the
      diagnosis of pre-diabetes and diabetes could increase the target population for
      preventive and therapeutic measures. Further cost-effectiveness studies are
      needed before the widespread diagnostic use of HbA(1c) can be recommended.

PMID- 21966957
TI  - STIM1/Orai1 contributes to sex differences in vascular responses to calcium in
      spontaneously hypertensive rats.
AB  - Sex differences in Ca2+-dependent signalling and homoeostasis in the vasculature
      of hypertensive rats are well characterized. However, sex-related differences in
      SOCE (store-operated Ca2+ entry) have been minimally investigated. We
      hypothesized that vascular protection in females, compared with males, reflects
      decreased Ca2+ mobilization due to diminished activation of Orai1/STIM1 (stromal
      interaction molecule 1). In addition, we investigated whether ovariectomy in
      females affects the activation of the Orai1/STIM1 pathway. Endothelium-denuded
      aortic rings from male and female SHRSP (stroke-prone spontaneously hypertensive
      rats) and WKY (Wistar-Kyoto) rats and from OVX (ovariectomized) or sham female
      SHRSP and WKY rats were used to functionally evaluate Ca2+ influx-induced
      contractions. Compared with females, aorta from male SHRSP displayed: (i)
      increased contraction during the Ca2+-loading period; (ii) similar transient
      contraction during Ca2+ release from the intracellular stores; (iii) increased
      activation of STIM1 and Orai1, as shown by the blockade of STIM1 and Orai1 with
      neutralizing antibodies, which reversed the sex differences in contraction during
      the Ca2+-loading period; and (iv) increased expression of STIM1 and Orai1.
      Additionally, we found that aortas from OVX-SHRSP showed increased contraction
      during the Ca2+-loading period and increased Orai1 expression, but no changes in
      the SR (sarcoplasmic reticulum)-buffering capacity or STIM1 expression. These
      findings suggest that augmented activation of STIM1/Orai1 in aortas from male
      SHRSP represents a mechanism that contributes to sex-related impaired control of
      intracellular Ca2+ levels. Furthermore, female sex hormones may negatively
      modulate the STIM/Orai1 pathway, contributing to vascular protection observed in
      female rats.

PMID- 21966958
TI  - Early smoking onset may promise initial pleasurable sensations and later
      addiction.
AB  - There is converging evidence suggesting a particular susceptibility to the
      addictive properties of nicotine among adolescents. The aim of the current study
      was to prospectively ascertain the relationship between age at first cigarette
      and initial smoking experiences, and to examine the combined effects of these
      characteristics of adolescent smoking behavior on adult smoking. It was
      hypothesized that the association between earlier age at first cigarette and
      later development of nicotine dependence may, at least in part, be attributable
      to differences in experiencing pleasurable early smoking sensations. Data were
      drawn from the participants of the Mannheim Study of Children at Risk, an ongoing
      epidemiological cohort study from birth to adulthood. Structured interviews at
      age 15, 19 and 22 years were conducted to assess the age at first cigarette,
      early smoking experiences and current smoking behavior in 213 young adults. In
      addition, the participants completed the Fagerstrom Test for Nicotine Dependence.
      Adolescents who smoked their first cigarette at an earlier age reported more
      pleasurable sensations from the cigarette, and they were more likely to be
      regular smokers at age 22. The age at first cigarette also predicted the number
      of cigarettes smoked and dependence at age 22. Thus, both the age of first
      cigarette and the pleasure experienced from the cigarette independently predicted
      aspects of smoking at age 22. 

PMID- 21966959
TI  - Invasive 'placebo' controls: have we lost sight of whom we are blinding?

PMID- 21966960
TI  - Alterations of acid-base balance, electrolyte concentrations, and osmolality
      caused by nonionic hyperosmolar contrast medium during pediatric cardiac
      catheterization.
AB  - OBJECTIVE: This prospective clinical observational study was conducted to
      investigate the effects of contrast medium on acid-base balance, electrolyte
      concentrations, and osmolality in children. BACKGROUND: For pediatric cardiac
      catheterization, high doses of nonionic hyperosmolar contrast medium are widely
      used. METHODS: Forty pediatric patients (age 0-16 years) undergoing cardiac
      angiography with more than 3 ml.kg(-1) of nonionic hyperosmolar contrast medium
      (Iomeprol) were enrolled, and the total amount of the contrast agent given was
      documented. Before and after contrast medium administration, a blood sample was
      collected to analyze electrolytes, acid-base parameters, osmolality, hemoglobin,
      and hematocrit. RESULTS: After cardiac catheterization, pH, hemoglobin,
      hematocrit, bicarbonate, base excess, sodium, chloride, calcium, anion gap and
      strong ion difference decreased, whereas osmolality increased significantly (base
      excess -1.8 +/- 1.8 vs -3.4 +/- 2.3, sodium 138 +/- 2.9 vs 132 +/- 4.1 mm,
      osmolality 284 +/- 5.7 vs 294 +/- 7.6 mosmol.kg(-1), P < 0.01). Seventy-eight
      percent of the children developed hyponatremia (sodium <135 mm). No changes were
      seen in pCO(2) , lactate, and potassium levels. CONCLUSIONS: Regarding the
      differential diagnosis of metabolic disturbances after pediatric cardiac
      catheterization, low-anion gap metabolic acidosis and hyponatremia should be
      considered as a possible side effect of the administered contrast medium.

PMID- 21966961
TI  - Transesophageal echocardiography (TEE) for pediatric cardiac surgery should
      routinely be performed and interpreted by a pediatric cardiac anesthetist:
      MODERATOR: Sulpicio Soriano.

PMID- 21966962
TI  - Combined ultrasound-guided femoral and lateral femoral cutaneous nerve blocks in
      pediatric patients requiring surgical repair of femur fractures.

PMID- 21966963
TI  - Reply to Aidan Cullen Re: Two-agent analgesia versus acetaminophen in children
      having bilateral myringotomies and tubes surgery, letter.

PMID- 21966964
TI  - A comparison of GlideScope videolaryngoscopy with direct laryngoscopy for
      nasotracheal intubation in children.

PMID- 21966965
TI  - A retrospective survey of brachial plexus blockade in pediatric hand trauma
      patients.

PMID- 21966966
TI  - Combined cardiac and noncardiac surgery in an infant with congenital rubella
      syndrome: an anesthetic challenge.

PMID- 21966967
TI  - Medication errors: time for a national audit?

PMID- 21966968
TI  - Medication errors - new approaches to prevention.

PMID- 21966969
TI  - Unusual complication in a neonate following tracheo-oesophageal fistula repair.

PMID- 21966970
TI  - The influence of activewear worn under standard work coveralls on whole-body heat
      loss.
AB  - This study evaluated the influence of activewear undergarments worn under the
      standard mining coveralls on whole-body heat exchange and change in body heat
      content during work in the heat. Each participant performed 60 min of cycling at
      a constant rate of heat production of 400 W followed by 60 min of recovery in a
      whole-body calorimeter regulated at 40 degrees C and 15% relative humidity
      donning one of the four clothing ensembles: (1) cotton underwear and shorts only
      (Control, CON); (2) Activewear only (ACT); (3) Coveralls+Cotton undergarments
      (COV+COT); or (4) Coveralls+Activewear undergarments (COV+ACT). In the latter two
      conditions a hard hat with earmuffs, gloves, and socks with closed toe shoes were
      worn. We observed that both COV+COT and COV+ACT resulted in a similar mean (+/
      SE) change in body heat content, which was significantly greater compared with
      the CON and ACT during exercise, suggesting that the rate of thermal strain was
      elevated to a similar degree in both coverall conditions (CON: 245+/-32 kJ; ACT:
      260+/-29 kJ; COV+COT: 428+/-36 kJ; COV+ACT: 466+/-15 kJ; p<0.001). During
      recovery, the negative change in body heat content was greater for both COV+COT
      and COV+ACT compared with the CON and ACT but similar between COV+COT and COV+ACT
      due to the greater amount of heat stored during exercise (CON: -83+/-16 kJ; ACT: 
      104+/-33 kJ; COV+COT: -198+/-30 kJ; COV+ACT: -145+/-12 kJ; p=0.048). Core
      temperatures and heart rate were also significantly elevated for the COV+COT and
      COV+ACT compared with the CON and ACT conditions during and following exercise
      (p<0.05). These results suggest that while activewear undergarments are not
      detrimental, they provide no thermoregulatory benefit when replacing the cotton
      undergarment worn under the standard coverall during work in the heat.

PMID- 21966971
TI  - Spinal cord injury causes more damage to fracture healing of later phase than
      ovariectomy in young mice.
AB  - The purpose of this study was to compare the effects of spinal cord injury (SCI)
      and ovariectomy (OVX) on femoral fracture healing of later phase in young mice.
      Sixty young female C57 mice were randomized into three groups: SCI, OVX, and age
      matched intact control. The femoral fracture was generated at 3 weeks after SCI
      or OVX. At 1 month after fracture, the femoral fracture area was evaluated
      through the healing status using radiograph; bone mineral density using dual X
      ray absorptometry; callus formation and mineralization and neovascularization in
      callus using micro-computed tomography; biomechanical analysis using testing
      machine; and histology analysis by staining with hematoxylin-eosin stain. SCI
      mice showed lower bone mineral density in the femoral callus as compared with OVX
      mice. Callus geometric microstructural parameters of the femora in SCI mice were
      significantly lower than OVX mice. SCI induced significant changes of
      biomechanical parameters in the femoral fracture healing area. The callus
      formation and callus neovascularization in SCI mice were significantly lower than
      in OVX mice. SCI induces more deterioration of fracture healing in the femoral
      diaphysis than OVX.

PMID- 21966972
TI  - Photodynamic therapy and the role of heat shock protein 70.
AB  - Photodynamic therapy (PDT) is an effective treatment for superficial epithelial
      skin cancers and is also being utilised for skin rejuvenation. PDT with porphyrin
      derived photosensitisers may be capable of inducing rapid cytochrome c release
      initiating apoptotic cascade via an activation of different caspases. Hsp70 has
      been demonstrated to directly bind to the caspase recruitment domain (CARD) of
      apoptotic-protease activating factor 1 (Apaf-1), thereby preventing the
      recruitment of oligomerisation of Apaf-1 and association of Apaf-1 with
      procaspase 9. Further, cytoplasmic Hsp70 rapidly translocates to the cell surface
      where it stabilises damaged membranes and preserves their integrity depending on
      the PDT dose. The induced cell surface expression and release of Hsp70 and its
      relevance for tumor response or skin rejuvenation is not fully understood, but
      seems to be of interest for monitoring, predicting or optimising treatment
      regimens. This review aims to summarise the current knowledge on PDT mediated
      cell signalling.

PMID- 21966977
TI  - Coexistence of flexural and follicular lichen planus.

PMID- 21966978
TI  - Acoustic startle hypersensitivity in Mceph mice and its effect on hippocampal
      excitability.
AB  - Current therapies and research for epilepsy concentrate mainly on controlling the
      disease, but not on prevention of its development and progression. This is partly
      due to the under-appreciated heterogeneity of the different epileptic syndromes,
      and a lack of knowledge about the underlying mechanisms of hypersensitivity and
      hypersynchrony in epilepsy development and spread. In this study we investigate
      mechanisms underlying the increased susceptibility to acoustic startle in a mouse
      model homozygous for the spontaneous megencephaly (mceph) mutation, which results
      in a lack of the functional potassium channel Kv1.1. Mceph mice are
      hypersensitive to acoustic startle, a response that is not seen in the wild-type
      (WT) littermates. After acoustic startle, a strong activation of astrocytes, as
      indicated by glial fibrillary acidic protein, occurred in the inferior colliculus
      and hippocampus. Both the hypersensitivity of acoustic startle as well as
      activation of astrocytes could be maintained at WT levels by pre-treating the
      Mceph mice with the anti-epileptic drug valproate. Furthermore, we utilized the
      Mceph mouse model to investigate whether acoustic startle-induced
      hypersensitivity has negative consequences for synchronous neuronal activity in
      other, non-auditory, systems and networks in the brain, such as the hippocampus.
      Our findings show that acoustic startle-induced hypersensitivity primes
      hippocampal networks by increasing their excitability, which results in increased
      strength of rhythmic network activity. Our results provide novel insights into
      the mechanisms that underlie the spread of hypersensitivity and hypersynchrony
      across functionally different parts of the brain.

PMID- 21966979
TI  - Reduced bone mineral density in hypertensive patients is associated with left
      ventricular diastolic dysfunction, not left ventricular hypertrophy.
AB  - Left ventricular (LV) hypertrophy and diastolic dysfunction are commonly observed
      in hypertensive patients, and have been demonstrated to be risk factors of
      chronic heart failure due to LV diastolic dysfunction. Recently, reduced bone
      mineral density has been found in hypertensive patients compared with healthy
      controls. However, relationships between bone mineral density and LV hypertrophy
      and diastolic dysfunction have not been fully assessed. We examined relationships
      between bone mineral density and both LV hypertrophy and diastolic dysfunction in
      38 hypertensive patients (23 males, 15 females; mean age 71 +/- 8 y) who had been
      treated with antihypertensive drugs for at least 1 year. The bone mineral density
      of the calcaneus was measured with a quantitative ultrasound measurement device
      (A-1000 EXPRESS/InSight, GE Healthcare, Horten, Norway), and the stiffness index
      was determined as a parameter of bone mineral density. Echocardiography was
      performed to measure the left ventricular mass index as a parameter of LV
      hypertrophy. Left ventricular diastolic dysfunction was also assessed by early
      diastolic mitral annular velocity (e'), and the ratio of early transmitral flow
      velocity (E) to e' (E/e'). The bone mineral density did not correlate with left
      ventricular mass index, but did correlate with e' (r = 0.453, P < .01) and E/e'
      (r = -0.359, P < .05). Thus, reduced bone mineral density in hypertensive
      patients is not associated with LV hypertrophy but with LV diastolic dysfunction.
      Hypertensive patients with reduced bone mineral density may have a high risk of
      chronic heart failure due to LV diastolic dysfunction as well as bone fractures
      due to osteoporosis.

PMID- 21966980
TI  - Novel orally active antimalarial thiazoles.
AB  - An aminomethylthiazole pyrazole carboxamide lead 3 with good in vitro
      antiplasmodial activity [IC(50): 0.08 MUM (K1, chloroquine and multidrug
      resistant strain) and 0.07 MUM (NF54, chloroquine sensitive strain)] and
      microsomal metabolic stability was identified from whole cell screening of a
      SoftFocus kinase library. Compound 3 also exhibited in vivo activity in the  P.
      berghei  mouse model at 4 * 50 mg/kg administration via the oral route, showing
      99.5% activity and 9 days survival and showed low in vitro cytotoxicity.
      Pharmacokinetic studies in rats revealed good oral bioavailability (51% at 22
      mg/kg) with a moderate rate of absorption, reasonable half-life (t(1/2) 3 h), and
      high volume of distribution with moderately high plasma and blood clearance after
      IV administration. Toward toxicity profiling, 3 exhibited moderate potential to
      inhibit CYP1A2 (IC(50) = 1.5 MUM) and 2D6 (IC(50) = 0.4 MUM) as well as having a
      potential hERG liability (IC(50) = 3.7 MUM).

PMID- 21966981
TI  - Chronic relapsing urticaria confined to injection sites of upper arms.
AB  - New ongoing urticarial lesions confined to former injection sites of vaccination
      and allergy immunotherapy were observed in an 8-year-old boy. This finding can be
      best explained as an isotopic response phenomenon.

PMID- 21966982
TI  - Effects of the association between the alpha-subunit thigh and the beta-Subunit
      EGF2 domains on integrin activation and signaling.
AB  - Integrin bidirectional signaling is mediated by conformational change. It has
      been shown that the separation of the alpha- and beta-subunit
      transmembrane/cytoplasmic tails and the lower legs is required for transmitting
      integrin bidirectional signals across the plasma membrane. In this study, we
      address whether the separation of the alphabeta knee is critical for integrin
      activation and outside-in signaling. By introducing three disulfide bonds to
      restrict dissociation of the alpha-subunit thigh domain and beta-subunit I-EGF2
      domain, we found that two of them could completely abolish integrin inside-out
      activation, whereas the other could not. This disulfide-bonded mutant, in the
      context of the activation mutation of the cytoplasmic domain, had intermediate
      affinity for ligands and was able to mediate cell adhesion. Our data suggest that
      there exists rearrangement at the interface between the thigh domain and the I
      EGF2 domain during integrin inside-out activation. None of the disulfide-bonded
      mutants could mediate cell spreading upon adhering to immobilized ligands,
      suggesting that dissociation of the integrin two knees is required for integrin
      outside-in signaling. Disrupting the interface by introducing a glycan chain into
      either subunit is sufficient for high affinity ligand binding and cell spreading.

PMID- 21966983
TI  - Surface-enhanced emission from single semiconductor nanoribbons.
AB  - Emission enhancement from single semiconductor CdSe nanoribbons by introduction
      of surface plasmon polaritons (SPPs) via Au contacts is studied. Scanning
      confocal microscopy is employed to investigate the emission enhancement behavior
      via photoluminescence measurements. Large enhancement factors of 77-130 at a peak
      emission of CdSe of ~710 nm are obtained, which are ascribed to the gain-assisted
      propagation of the short-range mode of SPPs. Our findings open the exciting
      possibilities for high-efficiency SPP-enhanced light-emitting devices based on
      luminous bodies with finite lateral dimensions.

PMID- 21966984
TI  - Asymmetric aziridination of cyclic enones using chiral diamine catalysts and its
      application to the total synthesis of (-)-agelastatin A.
AB  - The asymmetric aziridination of cyclic enones with N-tosyloxycarbamates, using N
      neopentyl 1,2-diphenylethylenediamine as a catalyst, and its application to the
      formal total synthesis of (-)-agelastatin A, using a one-pot silylation
      selenylation procedure and the regioselective aziridine-opening by an azide anion
      as key steps, are described.

PMID- 21966985
TI  - The value, limitations, and challenges of employing local experts in conservation
      research.
AB  - Evidence suggests that the involvement of local people in conservation work
      increases a project's chances of success. Involving citizen scientists in
      research, however, raises questions about data quality. As a tool to better
      assess potential participants for conservation projects, we developed a knowledge
      gradient, K, along which community members occupy different positions on the
      basis of their experience with and knowledge of a research subject. This gradient
      can be used to refine the citizen-science concept and allow researchers to
      differentiate between community members with expert knowledge and those with
      little knowledge. We propose that work would benefit from the inclusion of select
      local experts because it would allow researchers to harness the benefits of local
      involvement while maintaining or improving data quality. We used a case study
      from the DeHoop Nature Preserve, South Africa, in which we conducted multiple
      interviews, identified and employed a local expert animal tracker, evaluated the
      expert's knowledge, and analyzed the data collected by the expert. The expert
      animal tracker J.J. created his own sampling design and gathered data on mammals.
      He patrolled 4653 km in 214 days and recorded 4684 mammals. He worked from a
      central location, and his patrols formed overlapping loops; however, his data
      proved neither spatially nor temporally autocorrelated. The distinctive data
      collected by J.J. are consistent with the notion that involving local experts can
      produce reliable data. We developed a conceptual model to help identify the
      appropriate participants for a given project on the basis of research budget,
      knowledge or skills needed, technical literacy requirements, and scope of the
      project.

PMID- 21966986
TI  - Altered microRNA expression in mycosis fungoides.
AB  - BACKGROUND: MicroRNAs are small noncoding RNA molecules involved in the
      regulation of various physiological and pathological processes. Altered
      expression of different microRNAs has been observed in both solid tumours and
      haematological malignancies. OBJECTIVES: To investigate expression of several
      microRNAs in early and advanced mycosis fungoides (MF). METHODS: Biopsies were
      obtained from 43 patients with MF (18 early MF and 25 advanced MF) and 23 healthy
      volunteers. After microRNA isolation, reverse transcriptase reactions were
      performed, followed by cDNA amplification. The following microRNAs were analysed:
      miR-15a, miR-16, miR-155, let-7a, let-7d and let-7f. The relative amount of each
      microRNA was normalized according to the reference RNU48 level. RESULTS: Among
      the microRNAs studied, only MiR-155 was found to be slightly overexpressed in MF
      compared with healthy controls. Early MF showed a higher level of all analysed
      microRNAs after normalization against RNU48 level. Furthermore, metastatic MF
      demonstrated lower concentrations of let-7a, let-7d and let-7f when compared with
      MF limited to the skin. The univariate survival analysis and multivariate Cox's
      regression model revealed that the level of let-7a expression was an independent
      prognostic indicator. CONCLUSIONS: Altered expression of studied microRNAs and
      the differences between early and advanced MF may suggest that microRNAs play a
      significant role in MF pathogenesis. It seems that microRNAs could serve as
      potential therapeutic targets in the future.

PMID- 21966987
TI  - Fluxionality of hydrogen ligands in Fe(H)2(H2)(PEtPh2)3.
AB  - Extensive computational investigations along with additional quasielastic neutron
      scattering data were used to obtain a consistent picture of the extensive
      fluxionality of hydride and dihydrogen ligands in Fe(H)(2)(H(2))(PEtPh(2))(3)
      over a wide range of temperatures from 1.5 to 320 K. We were able to identify
      three different regimes in the dynamical processes based on activation energies
      obtained from line spectral broadening. The rotational tunneling lines (coherent
      exchange of the two hydrogens of the H(2) ligand) are broadened with increasing
      temperature by incoherent exchange up to about 80 K at which point they merge
      into a quasielastic spectrum from 100 K to about 225 K. The effective activation
      energies for the two regions are 0.14 and 0.1 kcal mol(-1), respectively. A third
      dynamical process with a higher activation energy of 0.44 kcal mol(-1) dominates
      above 225 K, which we attribute to a quantum dynamical exchange of dihydrogen and
      hydride ligands. Our detailed density functional theory (DFT) structural
      calculations involving the three functionals (B3LYP, TPSS, and wB97XD) provide a
      good account of the experimental structure and rotational barriers when only the
      hydrogen ligands are relaxed. Full relaxation of the "gas-phase" molecule,
      however, appears to occur to a greater degree than what is possible in the
      crystal structure. The classical dihydrogen-hydride exchange path involves a cis
      dihydrogen and tetrahydride structure with energies of 6.49 and 7.38 kcal mol(
      1), respectively. Experimental observation of this process with much lower
      energies would seem to suggest involvement of translational tunneling in addition
      to the rotational tunneling. Dynamics of this type may be presumed to be
      important in hydrogen spillover from metal particles, and therefore need to be
      elucidated in an effort to utilize this phenomenon.

PMID- 21966988
TI  - Quality of life in Chinese home-based advanced cancer patients: does awareness of
      cancer diagnosis matter?
AB  - The aim of this study was to assess the quality of life (QOL) of Chinese home
      based advanced-stage cancer patients and to evaluate the association between the
      disclosure of cancer diagnosis and QOL. An interview-based survey was conducted
      from December 2009 to June 2010 in the home-based hospice of the First Affiliated
      Hospital of Chongqing Medical University, China. The principal finding of this
      study demonstrated that patients who did not have knowledge of their diagnosis
      exhibited better physical and emotional QOL compared with those who had knowledge
      of their diagnosis.

PMID- 21966989
TI  - End-of-life decisions: a comparative survey on (teaching) experiences, views, and
      ethico-legal knowledge of final-year medical students in Germany and France.
AB  - BACKGROUND: Research on the teaching experiences and knowledge of medical
      students on end-of-life decisions in medicine is important because it provides
      information on the competency of future doctors with respect to an important
      field of clinical practice and can support the development of a curriculum.
      METHOD: A multiple-choice and free-text survey on the teaching experiences and
      knowledge of final-year medical students at the universities of Bochum (Germany;
      n=212) and Tours (France; n=108) regarding end-of-life decisions in medicine was
      conducted during the last months of their studies. RESULTS: Our results indicate
      that even though students had training in ethico-legal aspects of end-of-life
      care and participated in clinical practice there is considerable lack of
      knowledge among students with respect to the ethico-legal framework for the
      limitation of treatment at the end of life. CONCLUSION: The study indicates that
      even with the recent changes in both medical schools there seems to be a further
      need to prepare students better for end-of-life issues.

PMID- 21966990
TI  - Place of death and its determinants for patients with cancer in Singapore: an
      analysis of data from the Singapore Cancer Registry, 2000-2009.
AB  - AIMS: To describe the place of death for patients with cancer in Singapore from
      2000 to 2009, and determinants of death at home and in in-patient hospice
      compared to death in hospital. METHOD: Cross-sectional analysis of all patients
      registered with the Singapore Cancer Registry who had died in the study period
      (N=52120). Places of death were grouped as homes, in-patient hospices, hospitals
      and others. For determinants of death at home and in in-patient hospice,
      covariates adjusted for in logistic regression analyses were age group, gender,
      ethnic group, primary tumour site, stage at diagnosis, duration and cause of
      death. RESULTS: In the 10-year period, 52.9% of patients with cancer had died in
      the hospital, 30.3% died at home and 10.7% in in-patient hospice. Determinants of
      death at home were older age, female (odds ratio OR 1.23, 95% confidence
      interval, CI 1.17-1.29), Malay (OR 2.28, 95% CI 2.13-2.44), cancers of the colo
      rectum, liver, stomach, pancreas and nasopharynx (compared to lung cancer),
      duration of illness of 1-5 years (OR 1.40, 95% CI 1.34-1.48), primary cause of
      death being 'neoplasms' (OR 2.97, 95% CI 2.79-3.17). Determinants of death in in
      patient hospice were older age, distant metastasis (OR 1.35, 95% CI 1.21-1.50)
      and primary cause of death being 'neoplasms' (OR 20.07, 95% CI 16.05-25.09).
      CONCLUSION: Knowledge about place of death and its determinants will facilitate
      the planning of healthcare services to enable patients with terminal cancer to
      die at home and in in-patient hospices, thereby avoiding inappropriate
      hospitalization at the end of life.

PMID- 21966991
TI  - Feasibility of a telephone-based counseling program for informal caregivers of
      hospice patients.
AB  - OBJECTIVES: Informal caregivers of hospice patients experience multiple stressors
      that can negatively impact physical, psychological, and emotional health. The
      Caregiver Life Line (CaLL) study was a one-group, intervention-only feasibility
      study of a telephone cognitive-behavioral stress-management intervention
      consisting of 10 to 12 weekly telephone counseling calls designed specifically
      for informal caregivers of home-based hospice patients. METHODS: Caregivers, who
      were recruited via seven participating hospices, were assessed at baseline, 3,
      and 6 months. Psychosocial measures included depression, perceived stress,
      benefit finding, social support, and quality of life (QoL). Process evaluation
      was also conducted at 6 months. RESULTS: Of the 25 participants, 19 completed the
      12-week intervention. The mean age was 60.3 years; 91% were female and 70%
      married. Forty-eight percent were caring for a spouse; 51% were caring for a
      parent or other family member. Participating caregivers and hospice staff
      reported high levels of satisfaction with the intervention. Although the small
      sample size and lack of a control group limit our ability to assess the efficacy
      of the intervention, psychosocial outcomes changed in the expected direction and
      participants reported high levels of self-efficacy regarding their ability to
      implement the adaptive coping skills. Interestingly, we observed a decrease in
      physical QoL across the three time points. CONCLUSIONS: This pilot study
      demonstrated that the CaLL intervention is feasible and acceptable to informal
      hospice caregivers. This report describes important lessons learned from the
      pilot study with the intention of informing future intervention studies with this
      population.

PMID- 21966992
TI  - Loss of genes for DNA recombination and repair in the reductive genome evolution
      of thioautotrophic symbionts of Calyptogena clams.
AB  - BACKGROUND: Two Calyptogena clam intracellular obligate symbionts, Ca.
      Vesicomyosocius okutanii (Vok; C. okutanii symbiont) and Ca. Ruthia magnifica
      (Rma; C. magnifica symbiont), have small genomes (1.02 and 1.16 Mb, respectively)
      with low G+C contents (31.6% and 34.0%, respectively) and are thought to be in an
      ongoing stage of reductive genome evolution (RGE). They lack recA and some genes
      for DNA repair, including mutY. The loss of recA and mutY is thought to
      contribute to the stabilization of their genome architectures and GC bias,
      respectively. To understand how these genes were lost from the symbiont genomes,
      we surveyed these genes in the genomes from 10 other Calyptogena clam symbionts
      using the polymerase chain reaction (PCR). RESULTS: Phylogenetic trees
      reconstructed using concatenated 16S and 23S rRNA gene sequences showed that the
      symbionts formed two clades, clade I (symbionts of C. kawamurai, C. laubieri, C.
      kilmeri, C. okutanii and C. soyoae) and clade II (those of C. pacifica, C.
      fausta, C. nautilei, C. stearnsii, C. magnifica, C. fossajaponica and C.
      phaseoliformis). recA was detected by PCR with consensus primers for recA in the
      symbiont of C. phaseoliformis. A detailed homology search revealed a remnant recA
      in the Rma genome. Using PCR with a newly designed primer set, intact recA or its
      remnant was detected in clade II symbionts. In clade I symbionts, the recA coding
      region was found to be mostly deleted.In the Rma genome, a pseudogene of mutY was
      found. Using PCR with newly designed primer sets, mutY was not found in clade I
      symbionts but was found in clade II symbionts. The G+C content of 16S and 23S
      rRNA genes in symbionts lacking mutY was significantly lower than in those with
      mutY. CONCLUSIONS: The extant Calyptogena clam symbionts in clade II were shown
      to have recA and mutY or their remnants, while those in clade I did not. The
      present results indicate that the extant symbionts are losing these genes in RGE,
      and that the loss of mutY contributed to the GC bias of the genomes during their
      evolution.

PMID- 21966993
TI  - Increased ethanol intake in prodynorphin knockout mice is associated to changes
      in opioid receptor function and dopamine transmission.
AB  - The purpose of this study was to examine the role of the prodynorphin gene in
      alcohol sensitivity, preference and vulnerability to alcohol consumption.
      Handling-induced convulsion (HIC) associated to alcohol, alcohol-induced loss of
      righting reflex (LORR), hypothermic effects in response to acute ethanol
      challenge, blood ethanol levels (BELs), conditioned place preference, voluntary
      ethanol consumption and preference, tyrosine hydroxylase (TH), dopamine
      transporter (DAT) and proenkephalin (PENK) gene expression, and u-, delta- and
      kappa-opioid agonist-stimulated [S(35) ]- guanosine 5'-triphosphate-binding
      autoradiography were studied in prodynorphin knockout (PDYN KO) and wild-type
      (WT) mice. There were no differences in HIC, LORR or the decrease in body
      temperature in response to acute ethanol challenge between PDYN KO and WT mice.
      PDYN KO mice presented higher BEL, higher ethanol-conditioned place preference
      and more ethanol consumption and preference in a two-bottle choice paradigm than
      WT mice. These findings were associated with lower TH and higher DAT gene
      expression in the ventral tegmental area and substantia nigra, and with lower
      PENK gene expression in the caudate-putamen (CPu), accumbens core (AcbC) and
      accumbens shell (AcbSh) in PDYN KO. The functional activity of the u-opioid
      receptor was lower in the CPu, AcbC, AcbSh and cingulate cortex (Cg) of PDYN KO
      mice. In contrast, delta- and kappa-opioid receptor-binding autoradiographies
      were increased in the CPu and Cg (delta), and in the CPu, AcbC and Cg (kappa) of
      PDYN KO. These results suggest that deletion of the PDYN gene increased
      vulnerability for ethanol consumption by altering, at least in part, PENK, TH and
      DAT gene expression, and u-, delta- and kappa-opioid receptor functional activity
      in brain areas closely related to ethanol reinforcement.

PMID- 21966994
TI  - Conformation resolved induced infrared activity: trans- and cis-formic acid
      isolated in solid molecular hydrogen.
AB  - We report combined experimental and theoretical studies of infrared absorptions
      induced in solid molecular hydrogen by different conformers of formic acid
      (HCOOH, FA). FTIR spectra recorded in the H(2) fundamental region (4120-4160 cm(
      1)) reveal a number of relatively strong trans-FA induced Q-branch absorptions
      that are assigned by studying both FA-doped parahydrogen (pH(2)) and normal
      hydrogen (nH(2)) samples. The induced H(2) absorptions are also studied for HCOOD
      doped nH(2) crystals for both the trans and cis conformers that show resolvable
      differences. Samples containing >90% of the higher energy cis-HCOOD conformer are
      produced by in situ IR pumping of the OD stretching overtone of trans-HCOOD using
      narrow-band IR light. Minimum energy structures for 1:1 complexes of H(2) and FA
      are determined using ab initio methods. The measured differences in the cis-
      versus trans-HCOOD induced spectra are in qualitative agreement with the
      frequencies and intensities calculated for the identified cluster structures as
      discussed in terms of the model of specific interactions.

PMID- 21966995
TI  - Add-on fesoterodine for residual storage symptoms suggestive of overactive
      bladder in men receiving alpha-blocker treatment for lower urinary tract
      symptoms.
AB  - Study Type - Therapy (RCT) Level of Evidence 1b What's known on the subject? and
      What does the study add? Male lower urinary tract symptoms are often attributed
      to bladder outlet obstruction secondary to benign prostatic hyperplasia and
      treated with drugs targeting the prostate. However, many men with storage lower
      urinary tract symptoms may not respond adequately to these agents.
      Antimuscarinics, with or without an alpha-blocker, may be effective for the
      treatment of the storage symptoms of overactive bladder in some men. Flexible
      dose fesoterodine as an add-on treatment significantly improved urinary frequency
      and symptom bother, but not urgency episodes (primary endpoint), versus add-on
      placebo and was well tolerated in men with persistent overactive bladder symptoms
      despite receiving alpha-blocker. OBJECTIVE: * To evaluate flexible-dose
      fesoterodine vs placebo in men with persistent overactive bladder (OAB) symptoms
      despite receiving alpha-blocker treatment SUBJECTS AND METHODS: * This was a
      double-blind, 12-week, flexible-dose trial. * Men with persistent storage
      symptoms (>= 8 micturitions and >= 3 urgency episodes per 24 h) after receiving
      an alpha-blocker for >= 6 weeks were randomized to add-on fesoterodine 4 mg or
      placebo, with optional dose escalation to 8 mg at week 4 and reduction back to 4
      mg at week 8 (or matching placebo adjustments). * Subjects completed 3-day
      diaries, International Prostate Symptom Score (IPSS), Overactive Bladder
      Questionnaire (OAB-q), Patient Perception of Bladder Condition (PPBC), and
      Urgency Perception Scale (UPS) at baseline and weeks 4 and 12. RESULTS: * A total
      of 943 men were randomized and received at least one dose of study treatment
      (fesoterodine, n= 471; placebo, n= 472). * Among these, 251 (53%) in the
      fesoterodine group and 300 (64%) in the placebo group requested dose escalation
      at week 4 and 35 (7%) and 15 (3%) requested dose reduction at week 8. Changes
      from baseline to week 12 in urgency episodes (primary endpoint) in the
      fesoterodine (-3.2) and placebo (-2.9) groups were not significantly different
      (P= 0.196), but improvements in micturitions (P= 0.009) and OAB-q symptom bother
      score (P= 0.007) were significantly greater with fesoterodine. * At week 4,
      significantly greater improvements in micturitions (P= 0.006), severe urgency
      episodes (P= 0.006), IPSS storage score (P= 0.022), OAB-q symptom bother score
      (P= 0.004), and OAB-q health-related quality of life (P= 0.041), but not urgency
      episodes (P= 0.062), were observed with add-on fesoterodine. * Dry mouth
      (fesoterodine, 21%; placebo, 6%) and constipation (fesoterodine, 6%; placebo, 2%)
      were the most common adverse events. Dysuria and urinary retention were reported
      by 3% and 2% of subjects, respectively, in the fesoterodine add-on group vs 1%
      and <1% of subjects, respectively in the placebo add-on group. One subject in
      each group had acute urinary retention requiring catheterization. CONCLUSIONS: *
      Flexible-dose fesoterodine was well tolerated as an add-on treatment in men with
      persistent storage symptoms. * Changes in urgency episodes at week 12 (primary
      endpoint) and many secondary endpoints were not significantly different between
      fesoterodine and placebo add-on treatment; however, improvements in frequency and
      symptom bother were significantly greater with fesoterodine. * These data suggest
      that there remains a limited understanding of the optimal evaluation and
      treatment of men with LUTS.

PMID- 21966996
TI  - Evaluation of sampling methods for measuring exposure to volatile inorganic acids
      in workplace air. Part 2: Sampling capacity and breakthrough tests for sodium
      carbonate-impregnated filters.
AB  - In France, the MetroPol 009 method used to measure workplace exposure to
      inorganic acids, such as HF, HCl, and HNO3, consists of a closed-face cassette
      fitted with a prefilter to collect particles, and two sodium carbonate
      impregnated filters to collect acid vapor. This method was compared with other
      European methods during the development of a three-part standard (ISO 21438) on
      the determination of inorganic acids in workplace air by ion chromatography.
      Results of this work, presented in a companion paper, led to a need to go deeper
      into the performance of the MetroPol 009 method regarding evaluation of the
      breakthrough of the acids, both alone and in mixtures, interference from
      particulate salts, the amount of sodium carbonate required to impregnate the
      sampling filter, the influence of sampler components, and so on. Results enabled
      improvements to be made to the sampling device with respect to the required
      amount of sodium carbonate to sample high HCl or HNO3 concentrations (500 MUL of
      5% Na2CO3 on each of two impregnated filters). In addition, a PVC-A filter used
      as a prefilter in a sampling device showed a propensity to retain HNO3 vapor so a
      PTFE filter was considered more suitable for use as a prefilter. Neither the
      material of the sampling cassette (polystyrene or polypropylene) nor the sampling
      flowrate (1 L/min or 2 L/min) influenced the performance of the sampling device,
      as a recovery of about 100% was achieved in all experiments for HNO3, HCl, and
      HF, as well as HNO3+HF and HNO3+HCl mixtures, over a wide range of
      concentrations. However, this work points to the possibility of interference
      between an acid and salts of other acids. For instance, interference can occur
      through interaction of HNO3 with chloride salts: the stronger the acid, the
      greater the interference. Methods based on impregnated filters are reliable for
      quantitative recovery of inorganic volatile acids in workplace atmosphere but are
      valuable only in the absence of interferents.

PMID- 21966997
TI  - Cefixime and ceftriaxone susceptibility of Neisseria gonorrhoeae in Italy from
      2006 to 2010.
AB  - Neisseria gonorrhoeae resistance to cephalosporins, the currently recommended
      treatment, and treatment failures with cefixime have been reported worldwide. The
      purposes of the present study were (i) to examine the susceptibility of N.
      gonorrhoeae isolates isolated in Italy from 2006 through 2010 to cefixime (n =
      293) taking into account both European Committee on Antimicrobial Susceptibility
      Testing (EUCAST) and Clinical And Laboratory Standards Institute (CLSI) criteria
      for categorization; (ii) to determine the contribution to decreased/resistant
      susceptibility of mutations in the penA, mtrR, ponA and porB1b genes in a
      subsample of isolates; and (iii) to genotype the isolates showing decreased
      susceptibility or resistance to cefixime, by N. gonorrhoeae multi-antigen
      sequence typing (NG-MAST) and by pulsed-field gel electrophoresis (PFGE) to
      identify the predominant genotypes. Minimum inhibitory concentrations (MICs) were
      determined by the E-test and agar dilution method on 293 isolates and results
      were interpreted according to both EUCAST 2010 (MIC R >0.12 mg/L) and CLSI 2008
      (MIC R >0.25 mg/L) criteria. All isolates showed full susceptibility to
      ceftriaxone, whereas those with a MIC for cefixime >=0.125 mg/L were on the
      increase from 2008 through 2010. The same penA gene alterations were found among
      isolates with MICs close to the EUCAST breakpoint as the resistant ones, and they
      belong to ST1407. Seven isolates, belonging to various sequence types, showed a
      different por allele, though similar to the por 908 allele present in ST1407.
      PFGE divided strains ST1407 into two main groups confirming their genetic
      relationship.

PMID- 21966998
TI  - Effect of highly ordered single-crystalline TiO2 nanowire length on the
      photovoltaic performance of dye-sensitized solar cells.
AB  - One-dimensional semiconductor nanostructures grown directly onto transparent
      conducting oxide substrates with a high internal surface area are most desirable
      for high-efficiency dye-sensitized solar cells (DSSCs). Herein, we present a
      multicycle hydrothermal synthesis process to produce vertically aligned, single
      crystal rutile TiO(2) nanowires with different lengths between 1 and 8 MUm for
      application as the working electrode in DSSCs. Optimum performance was obtained
      with a TiO(2) nanowire length of 2.0 MUm, which may be ascribed to a smaller
      nanowire diameter with a high internal surface area and better optical
      transmittance with an increase in the incident light intensity on the N719 dye;
      as well as a firm connection at the FTO/TiO(2) nanowire interface.

PMID- 21966999
TI  - Darbepoetin enhances endothelium-dependent vasomotor function in patients with
      stable coronary artery disease only after preceding ischaemia/reperfusion.
AB  - Vasoprotective effects of erythropoietin in animal models are mediated by
      endothelium-derived NO and/or mobilization of EPCs (endothelial progenitor cells)
      and may be enhanced by ischaemia: whether they are present in humans is unknown.
      We examined whether the erythropoietin analogue darbepoetin improves FMD (flow
      mediated dilatation), a measure of endothelium-derived NO, and whether this is
      influenced by preceding I/R (ischaemia/reperfusion). A total of 36 patients (50
      75 years) with stable coronary artery disease were randomized to receive a single
      dose of darbepoetin (300 MUg) or saline placebo. FMD was measured at the brachial
      artery using high-resolution ultrasound. CD133+/CD34+/VEGFR2+ (vascular
      endothelial growth factor receptor 2) circulating EPCs were enumerated by flow
      cytometry. Measurements were made immediately before darbepoetin/placebo and at
      24 h, 72 h and 7 days. At 24 h, FMD was repeated after 20 min of I/R of the upper
      limb. A further group of 11 patients was studied according to the same protocol,
      all receiving darbepoetin, with omission of forearm I/R at 24 h. Immunoreactive
      erythropoietin peaked at 24 h and remained elevated at approximately 50-fold of
      baseline at 72 h. FMD did not differ significantly between groups at 24 h (before
      I/R). At 72 h (48 h after I/R), FMD was greater (by 2.3+/-0.5% in the darbepoetin
      compared with the placebo group, a 66% increase over baseline; P<0.001) and
      greater than FMD at the same time point without preceding I/R (P<0.01). Increases
      in CD133+/CD34+/VEGFR2+ cells after darbepoetin did not differ according to the
      presence or absence of preceding I/R. Preceding I/R is required for darbepoetin
      to enhance endothelial function, possibly by increasing expression of the
      erythropoietin receptor and by a mechanism likely to involve Akt/NO rather than
      circulating EPCs.

PMID- 21967000
TI  - Peritoneal keratin granulomas: cytohistological correlation in a case of
      endometrial adenocarcinoma with squamous differentiation.

PMID- 21967002
TI  - Energy-band engineering for improved charge retention in fully self-aligned
      double floating-gate single-electron memories.
AB  - We present a new fully self-aligned single-electron memory with a single pair of
      nano floating gates, made of different materials (Si and Ge). The energy barrier
      that prevents stored charge leakage is induced not only by quantum effects but
      also by the conduction-band offset that arises between Ge and Si. The dimensions
      and position of each floating gate are well-defined and controlled. The devices
      exhibit a long retention time and single-electron injection at room temperature.

PMID- 21967001
TI  - Matchmaking the B-cell signature of tolerance to regulatory B cells.
AB  - Confirmation of clinical tolerance requires the cessation of immunosuppressive
      drugs, which evoke immune reactivation and allograft rejection in all but the
      rare individuals who successfully transition into a state of operational
      transplantation tolerance. Therefore, the safe conduct of trials in
      transplantation tolerance requires two conditions: a sensitive and reliable means
      to identify individuals still being maintained on immunosuppression who are most
      likely to exhibit tolerance after immunosuppression is withdrawn and a
      noninvasive means that assesses the quality or robustness of the tolerant (TOL)
      state. Two recent studies attempting to identify a gene signature in peripheral
      blood of spontaneously TOL kidney transplant recipients made the unexpected
      observation that TOL, but not immune-suppressed transplant recipients, exhibited
      enriched B cells and B-cell transcripts in their blood. In concert with the
      emerging appreciation of a specialized subset of regulatory B cells (Bregs) that
      possess immune-modulatory function, these observations raise the possibility that
      Bregs play a critical role in the maintenance of tolerance to renal allografts in
      transplant patients. This review summarizes these recent findings and speculates
      on the relationship of Bregs to the maintenance of transplantation tolerance.

PMID- 21967005
TI  - Using I3 theory to clarify when dispositional aggressiveness predicts intimate
      partner violence perpetration.
AB  - Deriving hypotheses from I3 theory (pronounced "I-cubed theory"), the authors
      conducted 4 studies to clarify the circumstances under which dispositional
      aggressiveness predicts intimate partner violence (IPV) perpetration. Consistent
      with the hypothesis that this link would be stronger when inhibitory processes
      are weak rather than strong, Studies 1 and 2 demonstrated that dispositional
      aggressiveness was an especially robust predictor of IPV perpetration among
      people experiencing self-regulatory strength depletion. Consistent with the
      hypothesis that this Dispositional Aggressiveness * Inhibition interaction effect
      would be stronger when instigating triggers are strong rather than weak, Studies
      3 and 4 demonstrated that dispositional aggressiveness was an especially robust
      predictor of IPV perpetration among people characterized by both weak inhibition
      (poor executive control in Study 3, depletion in Study 4) and strong instigation
      (provocation in both studies). These effects were robust in studies employing
      experimental and nonexperimental designs, cross-sectional and longitudinal
      methods, dating and married participants, self-report and behavioral measures of
      IPV perpetration, and diverse operationalizations of all constructs. Discussion
      emphasizes the importance of incorporating instigating, impelling, and inhibiting
      processes into theoretical and empirical analyses of IPV perpetration.

PMID- 21967006
TI  - So far away from one's partner, yet so close to romantic alternatives: avoidant
      attachment, interest in alternatives, and infidelity.
AB  - Temptation pervades modern social life, including the temptation to engage in
      infidelity. The present investigation examines one factor that may put
      individuals at a greater risk of being unfaithful to their partner: dispositional
      avoidant attachment style. The authors hypothesize that avoidantly attached
      people may be less resistant to temptations for infidelity due to lower levels of
      commitment in romantic relationships. This hypothesis was confirmed in 8 studies.
      People with high, vs. low, levels of dispositional avoidant attachment had more
      permissive attitudes toward infidelity (Study 1), showed attentional bias toward
      attractive alternative partners (Study 2), expressed greater daily interest in
      meeting alternatives to their current relationship partner (Study 5), perceived
      alternatives to their current relationship partner more positively (Study 6), and
      engaged in more infidelity over time (Studies 3, 4, 7, and 8). This effect was
      mediated by lower levels of commitment (Studies 5-8). Thus, avoidant attachment
      predicted a broad spectrum of responses indicative of interest in alternatives
      and propensity to engage in infidelity, which were mediated by low levels of
      commitment.

PMID- 21967007
TI  - Separating method factors and higher order traits of the Big Five: a meta
      analytic multitrait-multimethod approach.
AB  - Though most personality researchers now recognize that ratings of the Big Five
      are not orthogonal, the field has been divided about whether these trait
      intercorrelations are substantive (i.e., driven by higher order factors) or
      artifactual (i.e., driven by correlated measurement error). We used a meta
      analytic multitrait-multirater study to estimate trait correlations after common
      method variance was controlled. Our results indicated that common method variance
      substantially inflates trait correlations, and, once controlled, correlations
      among the Big Five became relatively modest. We then evaluated whether two
      different theories of higher order factors could account for the pattern of Big
      Five trait correlations. Our results did not support Rushton and colleagues'
      (Rushton & Irwing, 2008; Rushton et al., 2009) proposed general factor of
      personality, but Digman's (1997) alpha and beta metatraits (relabeled by DeYoung,
      Peterson, and Higgins (2002) as Stability and Plasticity, respectively) produced
      viable fit. However, our models showed considerable overlap between Stability and
      Emotional Stability and between Plasticity and Extraversion, raising the question
      of whether these metatraits are redundant with their dominant Big Five traits.
      This pattern of findings was robust when we included only studies whose observers
      were intimately acquainted with targets. Our results underscore the importance of
      using a multirater approach to studying personality and the need to separate the
      causes and outcomes of higher order metatraits from those of the Big Five. We
      discussed the implications of these findings for the array of research fields in
      which personality is studied.

PMID- 21967008
TI  - Leveraging member expertise to improve knowledge transfer and demonstrability in
      groups.
AB  - Group success is dependent on both the knowledge of group members and the extent
      to which the group can access this knowledge. This research focuses on promoting
      effective knowledge transfer in group members by facilitating their use of extant
      knowledge when solving novel problems and examines how this affects subsequent
      discussion, decision making, and performance. Participants (N = 540) answered a
      series of estimation items individually or in a group. Sessions were recorded to
      provide insight into the group interactions. Facilitating knowledge transfer
      promoted (a) a more effective dialogue in which members were able to share more
      of their knowledge and discuss member expertise, (b) groups giving greater weight
      to better member preferences in their decision-making process, and (c) improved
      group performance relative to both average comparison individuals and to groups
      operating without this intervention. The effectiveness of promoting knowledge
      transfer in a group context relative to an individual context is discussed and
      group superiority is related to the concept of task demonstrability.

PMID- 21967009
TI  - Development of personality and the remission and onset of personality pathology.
AB  - The current study used the Longitudinal Study of Personality Disorders data set
      (Lenzenweger, 1999) to examine the development of personality traits in the
      context of the remission and onset of personality disorder (PD) symptoms. Despite
      high levels of stability, past research on the development of basic personality
      traits has also found a mean trend toward increased maturity and that individuals
      vary in their trajectories of trait development. Research on PD change has shown
      a similar pattern. We employed individual growth curve modeling to examine the
      relationship between personality trait development and PD symptom course. We
      found that both are indeed related and that remission in PD symptoms is
      associated with patterns of trait development associated with more rapid
      maturity. In contrast, deviating from the mean of trait development either
      through no change (i.e., stagnation) or change in the opposite direction (i.e.,
      regression) was associated with developing PD symptoms over the course of the
      study.

PMID- 21967010
TI  - Poikiloderma with neutropenia: report of three cases including one with
      calcinosis cutis.
AB  - Poikiloderma with neutropenia (PN), Clericuzio type (OMIM #604173) is a new,
      unique genodermatosis first described by Clericuzio et al (Am J Med Genet A,
      2011, 155, 337) in Navajo Indian population. This disease is characterized by
      poikiloderma that usually develops in the first year of life and is associated
      with nail abnormality, palmoplantar hyperkeratosis, chronic neutropenia, and
      recurrent infections. The rash typically starts from the extremities and spreads
      centripetally to involve the trunk, face, and ears. Recently, a homozygous
      mutation in the C16orf57 gene on chromosome 16q13 was identified as a strong
      candidate as the gene responsible for PN. We report three cases of PN whose
      clinical presentations, laboratory investigations, and C16orf57 mutation support
      the diagnosis of PN. One child has developed multiple painful calcinosis cutis
      lesions. Early-onset poikiloderma should prompt a complete blood count as a
      screening test.

PMID- 21967011
TI  - Atypical epidermolysis bullosa simplex with a missense keratin 14 mutation
      p.Arg125Cys.
AB  - Epidermolysis bullosa (EB) is a group of hereditary autosomal dominant bullous
      diseases. EB is divided into four major phenotypes: intraepidermal EB (or EB
      simplex), junctional EB, dermolytic EB and mixed EB (Kindler syndrome). EB
      simplex is further divided into three subtypes: localized EB simplex, Dowling
      Meara EB simplex and other generalized EB simplex. We report a 28-year-old man
      with EB simplex with a missense keratin 14 mutation p.Arg125Cys associated with
      clumping of keratin filaments and acantholysis in mainly the spinous cells and
      basal cells. Immunohistochemistry revealed that the broader expression of keratin
      5 and 14 was observed in the epidermis, while the expression of keratin 1/10 was
      quite normal. Dysregulated expression of keratin 5/14 may hinder some functions
      or roles of keratin 1/10, namely filament assembly of keratin 1/10 in spinous
      cell integrity, although the expression of keratin 1/10 was not affected and this
      has not been demonstrated before.

PMID- 21967016
TI  - In vivo wound healing and dermal matrix remodelling in response to fractional
      CO(2) laser intervention: clinicopathological correlation in non-facial skin.
AB  - PURPOSE: Ablative fractional photothermolysis is a new concept for treatment of
      aged skin. Despite the low frequency of side effects there are now several
      reports about scarring, especially in non-facial regions like the neck. Our study
      aimed to investigate the in vivo wound healing process and remodelling in an area
      prone to scarring using a fractional ablative CO(2) laser with three different
      energy protocols. MATERIALS AND METHODS: Six patients with photo-damaged skin
      received a single fractional ablative treatment using a 250-um scanning CO(2)
      laser. Three areas on the neck were treated with 50, 100 and 300 mJ/microbeam at
      densities of 200, 150 and 100/cm(2), respectively. Biopsies were taken from
      untreated skin (control) and 10 minutes, 3 days, 14 days, 21 days and 28 days
      post-intervention. RESULTS: Fractional ablation with higher energies resulted in
      increased total thermal damage. Overall, 50 mJ was effective up to the
      superficial dermis, 100 mJ up to the mid-dermis, and 300 mJ resulted in deep
      dermal ablation. The intensity of lymphocytic inflammation and dermal remodelling
      correlated with the total amount of thermal damage. At 300 mJ, granuloma was
      present and persisted for at least 4 weeks as opposed to clinical healing, which
      was completed < 2 weeks. CONCLUSIONS: With the above-mentioned low and medium
      parameter settings, ablative fractional photothermolysis is safe and effective in
      non-facial skin. However, dermal remodelling continues for up to 4 weeks, which
      should be the minimum space between treatment sessions. Higher energies may
      induce granuloma formation, possibly a sign of an overstrained remodelling
      capacity.

PMID- 21967017
TI  - Palladium-catalyzed oxidative carbocyclization/arylation of enallenes.
AB  - A stereoselective palladium-catalyzed oxidative carbocyclization/arylation of
      enallenes is described. The reaction shows wide tolerance toward highly
      functionalized arylboronic acids and results in a cis addition of two carbon
      moieties to an olefin in good to excellent yields.

PMID- 21967019
TI  - Olmesartan medoxomil treatment is associated with decreased plasma B-type
      natriuretic peptide levels in patients on hemodialysis.
AB  - BACKGROUND: High levels of plasma B-type natriuretic peptide (BNP) are associated
      with cardiac heart failure and death among patients on hemodialysis (HD). A
      recent study has demonstrated that the angiotensin II type 1 receptor blocker
      lowers BNP concentrations. Here, we examined whether the ability of olmesartan
      medoxomil (OM; a novel angiotensin II type 1 receptor blocker) to decrease plasma
      BNP levels is concentration dependent in hypertensive patients on HD. METHODS:
      This preliminary, observational, open-labeled prospective study included 24
      patients on HD who were assigned to one group treated with OM (n = 14) or to an
      age-matched control group that was conventionally treated (n = 10). Blood
      pressure (BP) was monitored in the morning and evening of a non-HD day and before
      each HD session, and plasma BNP, plasma aldosterone (PAC), plasma active renin
      (PARC), and OM concentrations were measured at baseline, 4, and 8 weeks after
      treatment. RESULTS: Plasma BNP levels were significantly decreased in the OM
      group, but remained unchanged in the control group after 4 and 8 weeks of
      treatment. Compared with the control group, OM was associated with increased PARC
      and decreased PAC levels. The OM concentrations at 4 and 8 weeks significantly
      correlated with depressed plasma BNP levels in accordance with multiple
      regression analysis adjusted for confounders including BP. CONCLUSION: These
      results suggest that OM can help to decrease plasma BNP levels via a
      concentration-dependent effect in patients on HD.

PMID- 21967018
TI  - Sodium alginate oligosaccharides attenuate hypertension and associated kidney
      damage in Dahl salt-sensitive rats fed a high-salt diet.
AB  - OBJECTIVES: In this article, the antihypertensive effects of sodium alginate
      oligosaccharides, enzymatic products of high molecular natural alginate from sea
      weeds, in Dahl salt-sensitive (Dahl S) rats were investigated. MATERIAL AND
      METHODS: Dahl S rats fed a high-salt (4% NaCl) diet were treated with sodium
      alginate oligosaccharides (4% or 8% w/w) for 7 weeks. Systolic blood pressure
      (SBP) was measured by the tail-cuff method, and hypertensive cardiovascular
      benefits and kidney damage were assessed. Glomerular function and morphological
      sclerosis were determined. RESULTS: SBP increased in an age-dependent manner in
      the untreated Dahl S rats. Sodium alginate oligosaccharide treatment attenuated
      the increase in SBP in a dose-dependent manner. The heart and aortic walls
      weighed less in the rats treated with sodium alginate oligosaccharides than in
      the untreated rats. The SBP reduction was associated with a decrease in urinary
      protein excretion and an increase in the creatinine clearance rate. Sodium
      alginate oligosaccharides significantly attenuated hypertensive glomerular
      sclerosis and arterial injury in the kidney. Fractional excretion of sodium
      (FENa) decreased in low-salt Dahl S rats and increased with a salt challenge. The
      alginate oligosaccharides decreased FENa in high-salt Dahl S rats. CONCLUSIONS:
      The results of this study suggest that sodium alginate oligosaccharides attenuate
      salt-induced hypertension in Dahl S rats. This reduction is associated with
      decreases in cardiovascular and renal damage.

PMID- 21967020
TI  - Effect of gender on sympathovagal imbalance in prehypertensives.
AB  - Although recently the incidence of prehypertension has increased considerably,
      the pathophysiological mechanisms and the effects of gender in its causation have
      not yet been fully elucidated. Therefore, in this study body mass index (BMI),
      waist-hip ratio (WHR), basal heart rate (BHR), blood pressure (BP), rate pressure
      product (RPP), and spectral indices of heart rate variability (HRV) were
      reordered and analyzed in normotensive and prehypertensive males and females. It
      was observed that low frequency-high frequency (LF-HF) ratio, the sensitive
      indicator of sympathovagal imbalance (SVI), is significantly more (P < .001) in
      male prehypertensives compared with female prehypertensives. Although SVI in
      prehypertensives was found to be due to both sympathetic activation and vagal
      inhibition, contribution of vagal withdrawal was prominent in males. The LF-HF
      ratio was significantly correlated with BMI, WHR, BHR, BP, and RPP, which was
      more prominent in male prehypertensives and the degree of correlation was more
      for WHR and diastolic pressure. It was concluded that vagal inhibition plays an
      important role in critical alteration of SVI in the genesis of prehypertension,
      especially in males, and WHR could be a better indicator of SVI in
      prehypertensives. It was suggested that prehypertensives should improve their
      vagal tone to restore the sympathovagal homeostasis.

PMID- 21967021
TI  - Association of body mass index with glomerular filtration rate in Japanese: a
      cross-sectional study in work-site population.
AB  - It has been shown that aging and hypertension are important risk factors to
      promote renal damage. However, little data are available on the effect of obesity
      on the progression of renal damage, especially in young and middle-aged
      individuals. The aim of this study was to determine the association between body
      mass index (BMI) and renal function evaluated by estimated glomerular filtration
      rate (eGFR) in Japanese men. We studied the cross-sectional association of BMI
      with eGFR in 3872 Japanese men in a work-site population (18-64 y; mean age 42.1
      +/- 0.2 y). Estimated glomerular filtration rate was calculated by a novel
      equation for Japanese men. Estimated glomerular filtration rate was negatively
      correlated with age, systolic blood pressure (SBP), hemoglobin A1c (HbA1c), and
      BMI. We performed multiple regression analysis, controlling for factors, such as
      SBP, low-density lipoprotein-cholesterol, gamma-glutamyl transpeptidase, age,
      HbA1c, and uric acid. The association between age and eGFR was highly
      statistically significant. In addition, BMI was still significantly associated
      with eGFR independently of SBP. Moreover, mean eGFR, which was adjusted for age,
      SBP, HbA1c, serum uric acid, and gamma-glutamyl transpeptidase, decreased from
      88.9 mL/min/1.73 m(2) in the first quartile of BMI to 87.5 mL/min/1.73 m(2) in
      the second, 86.9 mL/min/1.73 m(2) in the third, and 85.9 mL/min/1.73 m(2) in the
      fourth quartile (test for trend, P < .0001). These results show that a close
      relationship is present between obesity and decreased eGFR in Japanese men.
      Keeping appropriate body weight, in addition to appropriate blood pressure, in
      young and middle age may be important to prevent renal damage in older age.

PMID- 21967022
TI  - Prevalence, awareness, treatment, and control of hypertension among adults in
      Beijing, China.
AB  - Hypertension is an important modifiable risk factor for cardiovascular diseases.
      This study aimed to determine the up-to-date prevalence, awareness, treatment,
      and control of hypertension, and their related influencing factors in adults in
      Beijing, China. A cross-sectional study was conducted in 2008. A total of 5760
      adults aged 18-79 years were selected from the general population. Data from a
      standardized questionnaire, physical examination, and blood sample were obtained.
      The prevalence of hypertension was 35.5% (41.8% in men, 30.9% in women) and
      increased with age in both sexes. The prevalence was similarly high in urban
      (35.6%) and in rural (34.9%) areas. Body mass index (BMI) and waist circumference
      were independently associated with hypertension. Participants with diabetes
      and/or dyslipidemia had higher prevalence of hypertension than their
      counterparts. Among hypertensive patients, 42.5% were aware of the diagnosis,
      35.9% received treatment, and 11.8% had hypertension control. Awareness and
      treatment of hypertension were low in men, young people, and rural residents.
      Control of hypertension was lower in older people and those with lower
      educational attainment. High waist circumference (central obesity) resulted in
      low control of hypertension (odds ratio = 0.45). Our findings underscore the
      urgent need to develop a comprehensive health strategy for the prevention,
      detection, and control of hypertension to avert the cardiovascular disease
      epidemic in Beijing.

PMID- 21967023
TI  - Assessment on antihypertensive effect and safety of nifedipine controlled-release
      tablet administered at 80 mg/day in practical clinic.
AB  - In this study, the effect of nifedipine controlled-release tablets at a dose of
      80 mg/day (NCR80) on blood pressure (BP) and safety was investigated. In
      essential hypertension (n = 50, >140/90 mm Hg) despite a combined therapy with
      antihypertensive agents, NCR80 was administered instead of the previous
      antihypertensive agents and changes in BP and pulse rate (PR), side effects, and
      changes in laboratory test values were examined for 24 months. Thirty-three
      patients switched to NCR80 as the initial dose from the previous antihypertensive
      agents (Initial), while 17 patients started treatment at NCR40 and increased to
      NCR80 after 1-3 months (Up-titration). In the Initial group, BP decreased
      significantly and this significant reduction continued for 24 months, but not in
      the case of PR. In the Up-titration group, BP decreased significantly during the
      treatment with NCR40, and further reduced in 1-2 month(s) after NCR80. This
      significant reduction continued for 12 months, but not in the case of PR. The
      mean change in BP after increasing NCR40 to NCR80 was -16/-6 mm Hg at 6 months.
      When patients who received NCR80 were stratified into three grades according to
      the baseline systolic blood pressure level (SBP) (>=180, 160-179, and 140-159 mm
      Hg), the mean change in BP at 1 month was -55, -27, and -16 mm Hg, respectively.
      None of the 50 patients treated with NCR80 experienced any side effects and no
      abnormal change was observed in their laboratory test values. These findings
      suggested that NCR80 demonstrated the ability to control BP appropriately
      depending on the severity with favorable safety.

PMID- 21967024
TI  - The Relationship between coronary artery calcification as assessed by multi
      detector computed tomography and arterial stiffness.
AB  - Pulse wave analysis and intima-media thickness (IMT) of carotid artery are the
      non-invasive indicators of subclinical atherosclerosis. Coronary artery
      calcification (CAC) score measured by multi-detector computed tomography (MDCT)
      is well known as a predictor of coronary heart disease (CHD). We investigated the
      association between coronary calcification assessed by MDCT and extracoronary
      atherosclerosis measured by pulse wave analysis and IMT of carotid artery.
      Arterial stiffness and carotid IMT were measured consecutively in 133 patients
      who underwent their first coronary MDCT angiography due to chest pain. Patients
      were divided into three groups according to the CAC score (group 1, score = 0, n
      = 62; group 2, 0 < score < 400, n = 58; group 3, score >= 400, n = 13). The
      classification of CAC score was associated with age, prevalence of hypertension
      and dyslipidemia, systolic blood pressure, pulse pressure, brachial-ankle pulse
      wave velocity, percentage of brachial mean artery pressure, upstroke time (UT),
      augmentation index, and carotid IMT. In a multivariate analysis, age (P = .048),
      hypertension (P = .007), dyslipidemia (P = .24), and mean ankle UT (P = .038)
      were independent variables for the classification of CAC score. The UT of pulse
      wave was significantly associated with the CAC score. The increased UT of pulse
      wave might provide incremental risk prediction in addition to that defined by
      conventional CHD risk assessment.

PMID- 21967025
TI  - A slightly low hemoglobin level is beneficially associated with arterial
      stiffness in Japanese community-dwelling women.
AB  - Pulse wave velocity (PWV) is a simple and noninvasive method of measuring
      arterial stiffness for the assessment of cardiovascular disease in high-risk
      populations. This association may be further confounded by hemoglobin status,
      which is involved in the development of atherosclerosis. We randomly recruited
      120 men and 223 women aged 69 +/- 9 and 68 +/- 7 years, respectively, during
      their annual health examination in a single community. Arterial stiffness was
      evaluated by brachial-ankle PWV (baPWV). The value of baPWV was different from
      men and women. In men, baPWV was not related to hemoglobin levels (r = 0.013, P =
      .886), but in women baPWV increased significantly and progressively with
      increased hemoglobin levels (r = 0.276, P < .001). Stepwise multiple regression
      analysis using the baPWV as objective variables, adjusted for confounding factors
      as explanatory variables, showed that only in women, hemoglobin levels (beta =
      0.165, P = .001) as well as age (beta = 0.268, P < .001), body mass index (BMI;
      beta = -0.165, P < .001), systolic blood pressure (SBP; beta = 0.429, P < .001),
      prevalence of antihypertensive (beta = 0.154, P = .002), heart rate (HR; beta =
      0.108, P = .017), and antilipidemic medication (beta = 0.094, P = .036), and
      estimated glomerular filtration rate (eGFR; beta = -0.147, P = .003) were
      significantly and independently associated with baPWV. Multivariate-adjusted
      baPWV was significantly higher in hemoglobin groups of >=12.7 g/dL (Group-2,
      Group-4) than in the lowest hemoglobin group (10.0-12.6 g/dL; P = .032). A
      slightly low hemoglobin level was beneficially associated with arterial stiffness
      in community-dwelling women but not men.

PMID- 21967026
TI  - Effects of lisinopril, irbesartan, and amlodipine on the thrombogenic variables
      in the early and late stages of the treatment in hypertensive patients.
AB  - Regulation of the fibrinolytic balance between plasminogen activators and
      inhibitors is modulated by the renin-angiotensin system (RAS). Impaired
      fibrinolytic function, characterized by increased plasminogen activator inhibitor
      type 1 (PAI-1) levels and decreased tissue plasminogen activator (t-PA) activity,
      has been found in patients with hypertension and may account in part for the
      increased risk of atherosclerosis and its clinical complications in these
      patients. In this regard, data from the literature indicate that different
      antihypertensive drugs may vary in their influence on fibrinolysis. Angiotensin
      converting enzyme (ACE) inhibitors (ACE-I) have generally been shown to improve
      the fibrinolytic balance by reducing plasma PAI-1 levels. Calcium-channel
      blockers (CCB) have been reported to increase t-PA activity, and angiotensin
      receptor blockers (ARB) seem to be neutral in their effect. In the light of these
      data, this study aimed to compare the effects of ACE-I, ARB, and CCB on the
      fibrinolytic system in the early and late stages of the treatment in hypertensive
      patients. These data that the beneficial effect of RAS inhibition on fibrinolysis
      related to decrease in Ang II during early period of treatment. Amlodipine may
      also improve thrombogenic risk related to lowering the effect on increased
      platelet activation reflected by p-selectin. The greater improvement in the early
      and late stages of the fibrinolytic balance because of the combined action of RAS
      inhibition and Ca antagonism represents a further indication to the use of
      combinations of RAS inhibition (ACE-I or ARB) and CCB in the treatment of
      hypertension.

PMID- 21967027
TI  - The relationship between resistant hypertension and arterial stiffness.
AB  - OBJECTIVES: With growing awareness of arterial stiffness (AS) in the past 10
      years, it was realized that resistant hypertension (RH) and AS share the same
      associated conditions such as older age, isolated systolic hypertension (HT),
      obesity, chronic kidney disease (CKD), and so on. Until now, there is no study
      investigating the role of AS in RH. In our study we aimed to determine whether
      there is an association between RH and AS. METHODS: Among 87 patients enrolled in
      this study, 30 were resistant hypertensives (Group 1), 29 were controlled
      hypertensives (Group 2), and 28 were normotensives (Group 3). Arterial stiffness
      was measured by both applanation tonometry and echocardiography; augmentation
      index, pulse wave velocity (PWV), aortic strain, and aortic distensibility were
      recorded in each patient. Diastolic function parameters were also assessed.
      RESULTS: In resistant hypertensive group, augmentation index and PWV were
      significantly higher than Group 2 and Group 3 (P = .03 and P < .01). Aortic
      strain and aortic distensibility parameters were significantly lower in RH group
      (P < .01 and P < .01). Arterial stiffness parameters were similar among Group 2
      and Group 3. Among diastolic function parameters, left atrial volume index and
      left ventricular mass index significantly differ between groups. These two
      parameters were significantly lower in control group (P < .01 and P = .02)
      whereas similar in Group 1 and Group 2. Systolic blood pressure (SBP) and
      diastolic blood pressure (DBP) levels were significantly different between groups
      as expected. When the correlation between two methods of AS was analyzed, a
      significant strong inverse correlation was found between echocardiographic and
      tonometric parameters. CONCLUSION: Arterial stiffness was found to be associated
      with RH. The inconsistency of this association in controlled hypertensives
      suggests a possible role of AS in RH pathogenesis. This study also showed that
      aortic strain and distensibility correlate well with the PWV which is the gold
      standard in the assessment of AS. This finding is important for the evaluation of
      AS more commonly in daily practice as echocardiography is a more feasible device
      than applanation tonometry.

PMID- 21967028
TI  - Frequency ranges of heart rate variability related to autonomic nerve activity in
      the mouse.
AB  - Mice have gained more and more attention in recent years and been widely used in
      transgenic experiments. Although the number of researches on the heart rate
      variability (HRV) of mice has been gradually increasing, a consensus on the
      frequency ranges of autonomic modulation has not been established. Therefore, the
      main purpose of this study was to find a HRV "prototype" for conscious mice in
      the state of being motionless and breathing regularly (called "genuinely
      resting"), and to determine the frequency ranges corresponding to the autonomic
      modulation. Further, whether these frequencies will change when the mice move
      freely was studied to evaluate the feasibility of the HRV spectrum as an index of
      the autonomic modulation of mice. The recording sites were specially arranged to
      simultaneously obtain the electrocardiography and electromyography data to be
      provided for the use of HRV analysis and motion monitoring, respectively. The
      states of being motionless and breathing regularly as judged from the
      electromyography results were selected as a genuine resting state of a conscious
      mouse. The frequencies related to autonomic modulation of HRV were determined by
      comparing the spectrum changes before and after blockades of the autonomic tone
      by different pharmaceutical agents in both the genuine resting state and freely
      moving states. Our results showed that the HRV of mice is not suitable for
      indexing sympathetic modulation; however, it is possible to use the spectral
      power in the frequency range between 0.1 and 1 Hz as an index of parasympathetic
      modulation.

PMID- 21967029
TI  - Vasodilator effect of Phlomis bracteosa constituents is mediated through dual
      endothelium-dependent and endothelium-independent pathways.
AB  - This study describes the vasorelaxant potential of some pure compounds isolated
      from Phlomis bracteosa L. marrubiin, phlomeoic acid, and two new constituents
      labeled as RA and RB. In rat thoracic aortic rings denuded of endothelium,
      marrubiin, phlomeoic acid, RA, and RB caused relaxation of high K(+) (80 mM) and
      phenylephrine (1 MUM)-induced contractions at the concentration range of 1.0-1000
      MUg/mL. Marrubiin, phlomeoic acid, RA, and RB concentration dependently (3.0-10
      MUg/mL) shifted the Ca(++) curves to the right obtained in Ca(++)-free medium.
      The vasodilator effect of marrubiin, phlomeoic acid, RA, and RB was partially
      blocked by N(omega)-nitro-L-arginine methyl ester in endothelium-intact aorta
      preparations. These results reveal that P. bracteosa constituents: marrubiin,
      phlomeoic acid, RA, and RB exhibit vasodilator action occurred via a combination
      of endothelium-independent Ca(++) antagonism and endothelium-dependent N(omega)
      nitro-L-arginine methyl ester-sensitive nitric oxide-modulating mechanism.

PMID- 21967030
TI  - Validation of the Parama-Tech PS-501 device for office blood pressure measurement
      according to the international protocol.
AB  - The PS-501 device (Parama-Tech, Fukuoka, Japan), an automated device for office
      blood pressure measurement based on the Korotkoff method and designed for
      professional use in clinical settings, was validated. Consecutive outpatients
      with hypertension and >=30 years old at an outpatient hypertension clinic were
      recruited. According to the European Society of Hypertension protocol, 33
      participants were included in the validation study (phase 1, n = 15; phase 2, n =
      18). The cuff deflation rate can be selected manually from 2, 3, and 4 mm
      Hg/beat. The validation was performed with the device deflating at a rate of 2 mm
      Hg/beat. All blood pressure readings were measured on the left arm. The tested
      device passed all criteria for both systolic and diastolic blood pressure
      measurements. The mean (+/- standard deviation) differences in systolic and
      diastolic blood pressure between the tested device and the mean of observer
      readings were -1.9 +/- 4.6 and -2.5 +/- 2.9 mm Hg, respectively. The PS-501
      device for office blood pressure measurement passed all the validation criteria
      of the European Society of Hypertension and can therefore be recommended for
      clinical use in an adult population.

PMID- 21967031
TI  - Blood pressure and metabolic effect of a combination of lercanidipine with
      different antihypertensive drugs in clinical practice.
AB  - The aim of this study is to assess the blood pressure (BP) and metabolic effects
      of lercanidipine when combined with other classes of first-line antihypertensive
      drugs in day-to-day clinical practice. For this study, we consecutively enrolled
      162 patients with uncomplicated primary hypertension, who are partial responders
      to the treatment with lercanidipine over a period of 24 months. Patients were
      then allocated to the combination of lercanidipine (10-20 mg/day) with beta
      blockers, diuretics, angiotensin-converting enzyme inhibitors, and angiotensin-II
      receptor blockers according to compelling indications (if any) and/or suggestions
      of European Society of Hypertension-European Society of Cardiology (ESH-ESC)
      guidelines. All the enrolled patients completed the study and no adverse drug
      reaction was registered during the research period. The association of a second
      drug with lercanidipine determined an additional BP decrease of either systolic
      BP or diastolic BP independently from the type of drug added (P always <.05). The
      additional effect of lercanidipine appears widely distributed with no significant
      differences in the size of BP decrease. From the metabolic point of view, the
      addition of a second drug did not determine a significant variation in the serum
      levels of total cholesterol, low-density lipoprotein cholesterol, and high
      density lipoprotein cholesterol (P always >.05). Conversely, a significant
      decrease in fasting plasma glucose and serum levels of triglycerides has been
      observed in patients where lercanidipine has been combined with an angiotensin
      converting enzyme inhibitor or an angiotensin-II receptor blocker. In conclusion,
      in our study we observed that lercanidipine-based protocols are well tolerated
      and efficacious in reducing BP. Moreover, the association of lercanidipine with
      renin-angiotensin system blockers is also associated with significant
      improvements in triglycerides and fasting plasma glucose.

PMID- 21967032
TI  - No effect of short-term hypertension on bone matrix mineralization in a surgical
      animal model in immature rabbits.
AB  - Epidemiological studies show that arterial hypertension is associated with bone
      loss and an increased risk of fractures. Bone material properties are essential
      for bone strength. However, little is known about the effects of hypertension on
      bone matrix mineralization. Genetic animal models of hypertension are not ideal
      for studying bone matrix properties since these mutations may affect
      mineralization per se. The purpose of this study was to evaluate the effects of
      short-term hypertension on bone mineral density distribution (BMDD) using
      quantitative backscattered electron imaging in the proximal humerus in an
      established surgical model of pressure-overload cardiac hypertrophy in immature
      rabbits. Banding of the descending aorta was performed in 10-day-old rabbits (n =
      4). Systolic blood pressure was elevated at all timepoints in the upper extremity
      but reached statistical significance at 5 and 6 weeks of age (+30.1% and +25.1 mm
      Hg; P < 0.05 each, respectively). Diastolic blood pressure was not affected. The
      left proximal humerus was harvested at 6 weeks of age, which is the maximum time
      in this animal model. Four non-operated, matched animals served as controls. Bone
      mineral density distribution parameters were determined in the epiphyseal and
      metaphyseal regions of the proximal humerus. The bone mineral density
      distribution parameters which describe the degree and heterogeneity of
      mineralization as well as the amount of low mineralized matrix showed no
      significant differences. Moreover no difference in bone length was found. Our
      study indicates that short-term elevation of blood pressure has no effects on
      bone matrix mineralization in this surgical model of pressure-overload cardiac
      hypertrophy in immature rabbits.

PMID- 21967033
TI  - The effect of admission blood pressure on the prognosis of patients with
      intracerebral hemorrhage that occurred during treatment with aspirin, warfarin,
      or no drugs.
AB  - BACKGROUND: Hypertension is the most important modifiable risk factor for
      intracerebral hemorrhage (ICH), but blood pressure (BP) management during the
      acute phase of ICH is still controversial. Approximately one-fourth of ICHs occur
      during treatment with warfarin or aspirin. AIM: This study was designed to
      determine the effect of admission BP on the early prognosis of ICH patients by
      dividing them into three groups (warfarin, aspirin, and no drugs). METHODS: Three
      hundred and sixty-nine patients with supratentorial ICH were divided into three
      groups according to medication. Each group was evaluated in terms of prognosis
      and the risk for mortality based on the modified Rankin Scale (mRS) score at
      discharge (good prognosis: mRS <= 3; poor prognosis: mRS > 3). The effect of
      admission BP on prognosis was evaluated for each group. RESULTS: The in-hospital
      mortality rate was 72% for ICH patients treated with warfarin, 41.6% for ICH
      patients treated with aspirin, and 35% for ICH patients treated with no drugs.
      Admission mean arterial blood pressure (MABP) values were higher in patients with
      poor prognosis compared with patients with good prognosis for the aspirin (P =
      .002) and no-drug (P = .001) groups, but not in the warfarin (P = .067) group.
      CONCLUSION: A high MABP at admission was found to be an independent predictor of
      poor prognosis for ICH patients treated with aspirin or with no drugs, but not
      for ICH patients treated with warfarin.

PMID- 21967034
TI  - Isolation of talathermophilins from the thermophilic fungus Talaromyces
      thermophilus YM3-4.
AB  - Six indole alkaloids with various levels of prenylation were isolated from the
      thermophilic fungus  Talaromyces thermophilus  strain YM3-4. Their structures
      were identified by NMR and MS spectroscopic analyses. Compounds 1 and 2 are new
      analogues of the key versatile precursor notoamide E. Compound 3 is a novel
      analogue of preechinulin, and compound 4 was reported as a natural occurring
      cyclo(glycyltryptophyl) for the first time. The metabolite profile of this
      thermophilic organism displayed a biosynthetic pathway for talathermophilins.

PMID- 21967035
TI  - Low-dose total skin electron beam therapy as a debulking agent for cutaneous T
      cell lymphoma: an open-label prospective phase II study.
AB  - BACKGROUND: Total skin electron beam therapy (TSEBT) is a powerful treatment for
      cutaneous T-cell lymphoma (CTCL). Based on the occurrence of relapses with low
      radiation doses, doses of 30-36Gy are commonly used but most patients still
      eventually relapse and repeat treatment courses are limited due to the cumulative
      toxicity. Complete response (CR) rates are about 60-90% for T2-4 stages with a 5
      year relapse-free survival of 10-25% for stages IB-III. OBJECTIVES: To evaluate
      prospectively the efficacy of low-dose TSEBT (10Gy) in terms of complete
      cutaneous response rate, overall response rate and response duration in CTCL.
      METHODS: Ten patients with stage IB-IV mycosis fungoides (MF) were treated in an
      open-label manner with four fractions of TSEBT 1Gy weekly to a total skin dose of
      10Gy. Treatment responses were assessed at 1 and 3months after treatment and
      subsequently at least every 6months for a total period of 2years or to disease
      relapse or progression. RESULTS: Patients achieved an overall response rate of
      90%. The rate of CR or very good partial response (VGPR; <1% skin affected with
      patches/plaques) was 70%. The median response duration was 5.2months (range 83
      469days) for CR and VGPR. Adverse effects were generally mild to moderate in
      severity. CONCLUSIONS: Low-dose TSEBT (10Gy) gave a satisfactory response rate
      and was well tolerated in patients with MF stage IB-IV. Future studies should
      determine if the combination of low-dose TSEBT with other agents could increase
      the rate of CR and response duration.

PMID- 21967036
TI  - Environmental enrichment compensates for the effects of stress on disease
      progression in Tg2576 mice, an Alzheimer's disease model.
AB  - Various environmental factors are known to influence the onset and progression of
      Alzheimer's disease (AD). Environmental enrichment was reported to improve
      cognitive performance in various Alzheimer's transgenic mice via an amyloid
      related or unrelated mechanism. However, stress has been found to accelerate
      amyloid deposition and cognitive deficits in many AD models. The aim of this
      study was to determine whether environmental enrichment compensates for the
      effects of stress on disease progression in the Tg2576 mice, an established AD
      model. We housed Tg2576 mice under environmental enrichment, enrichment plus
      stress, stress, or control conditions at 3 months of age. In this study, we first
      report that environmental enrichment counteracts the effects of stress in terms
      of cognitive deficits, tau phosphorylation, neurogenesis, and neuronal
      proliferation during AD-like disease progression. These results strongly
      implicate the importance of environmental factors as a major modulator for the
      disease progression of AD.

PMID- 21967037
TI  - Involvement of hippocampal phosphatidylethanolamine-binding protein in morphine
      dependence and withdrawal.
AB  - Drug addiction is thought to result from an intractable and aberrant learning and
      memory in response to drug-related stimulation, and cholinergic neurotransmission
      plays an important role in this process. Phosphatidylethanolamine-binding protein
      (PEBP) is the precursor of the hippocampal cholinergic neurostimulating peptide
      (HCNP), an 11 amino acid peptide that enhances the production of choline
      acetyltransferase (ChAT) and assists in the development of cholinergic
      projections from the medial septal nuclei to the hippocampus. However, whether
      PEBP is involved in drug addiction remains unclear. In the present study, PEBP
      expression in the hippocampus, as detected by proteomics analysis, was found to
      be dramatically up-regulated after rats received chronic morphine treatment.
      Western blotting analysis revealed a specific up-regulation of PEBP expression in
      the hippocampus but not in any other brain regions assessed. A down-regulation of
      hippocampal PEBP levels induced by antisense oligodeoxynucleotides resulted in
      aggravated morphine dependence. Together, these findings indicate that PEBP is
      involved in morphine dependence. Moreover, the time course of PEBP expression
      changes and ChAT activity was investigated during chronic morphine treatment and
      withdrawal. The results showed that the hippocampal PEBP levels were up-regulated
      during chronic morphine treatment and returned to the baseline 3 days after
      withdrawal, after which PEBP levels were persistently up-regulated for 28 days
      after withdrawal. The changes in hippocampal ChAT activity followed a pattern
      that was similar to that of the PEBP levels. Taken together, these results
      suggest that hippocampal PEBP is involved in morphine dependence and withdrawal,
      perhaps through modulating cholinergic transmission in the hippocampus.

PMID- 21967039
TI  - Structural variability in Ag(I) and Cu(I) coordination polymers with thioether
      functionalized bis(pyrazolyl)methane ligands.
AB  - We present here two ligand classes based on a bis(pyrazolyl)methane scaffold
      functionalized with a rigid (-Ph-S-Ph) or flexible (-CH(2)-S-Ph) thioether
      function: L(R)PhS (R = H, Me) and L(R)CH(2)S (R = H, Me, iPr). The X-ray
      molecular structures of Ag(I) and Cu(I) binary complexes with L(R)PhS or
      L(R)CH(2)S using different types of counterions (BF(4)(-), PF(6)(-), and
      CF(3)SO(3)(-)) are reported. In these complexes, the ligands are N(2) bound on a
      metal center and bridge on a second metal with the thioether group. In contrast,
      when using triphenylphosphine (PPh(3)) as an ancillary ligand, mononuclear
      ternary complexes [M(L)PPh(3)](+) (M = Cu(I), Ag(I); L = L(R)PhS, L(R)CH(2)S) are
      formed. In these complexes, the more flexible ligand type, L(R)CH(2)S, is able to
      provide the N(2)S chelation, whereas the more rigid L(R)PhS ligand class is
      capable of chelating only N(2) because the thioether function preorganized, as it
      did in the coordination polymers, to point away from the metal center. Rigid
      potential-energy surface scans were performed by means of density functional
      theory (DFT) calculations (B3LYP/6-31+G) on the two representative ligands,
      L(H)PhS and L(H)CH(2)S. The surface scans proved that the thioether function is
      preferably oriented on the opposite side of the bispyrazole N(2) chelate system.
      These results confirm that both ligand classes are suitable components for the
      construction of coordination polymers. Nevertheless, the methylene group that
      acts as a spacer in L(H)CH(2)S imparts an inherent flexibility to this ligand
      class so that the conformation responsible for the N(2)S chelation is
      energetically accessible.

PMID- 21967038
TI  - Diversification and the rate of molecular evolution: no evidence of a link in
      mammals.
AB  - BACKGROUND: Recent research has indicated a positive association between rates of
      molecular evolution and diversification in a number of taxa. However debate
      continues concerning the universality and cause of this relationship. Here, we
      present the first systematic investigation of this relationship within the
      mammals. We use phylogenetically independent sister-pair comparisons to test for
      a relationship between substitution rates and clade size at a number of taxonomic
      levels. Total, non-synonymous and synonymous substitution rates were estimated
      from mitochondrial and nuclear DNA sequences. RESULTS: We found no evidence for
      an association between clade size and substitution rates in mammals, for either
      the nuclear or the mitochondrial sequences. We found significant associations
      between body size and substitution rates, as previously reported. CONCLUSIONS:
      Our results present a contrast to previous research, which has reported
      significant positive associations between substitution rates and diversification
      for birds, angiosperms and reptiles. There are three possible reasons for the
      differences between the observed results in mammals versus other clades. First,
      there may be no link between substitution rates and diversification in mammals.
      Second, this link may exist, but may be much weaker in mammals than in other
      clades. Third, the link between substitution rates and diversification may exist
      in mammals, but may be confounded by other variables.

PMID- 21967040
TI  - Neonatal herpes simplex virus infections in Switzerland: results of a 6-year
      national prospective surveillance study.
AB  - A large variation in neonatal herpes incidence is observed in USA and Europe.
      Better knowledge of neonatal herpes epidemiology is important to inform local
      prevention strategies. Between 2002 and 2008, the Swiss Paediatric Surveillance
      Unit reported prospectively proven neonatal herpes simplex virus infections.
      During the study period seven cases were declared, for an incidence of
      1.6/100,000 (95% CI 0.64-3.28/100,000) live births. This is one of the lowest
      incidences of neonatal herpes reported.

PMID- 21967041
TI  - Gestational surrogacy after intra-operative oocyte collection in a
      hysterectomised woman diagnosed with endometrial cancer.

PMID- 21967042
TI  - Theoretical investigation of Raman optical activity signatures of Troger's base.
AB  - The Raman and VROA spectra of (S,S)-Troger's base are simulated. We mainly
      discuss the peaks in the 1140-1400 cm(-1) wavenumber range where an intense VROA
      signature is found. In this range, nearly all of the Raman-active bands belong to
      the irreducible representation A (C(2) point group), whereas no such observation
      is made for the VROA spectrum. The vibrational normal modes associated with the
      peaks in this range mainly consist of wagging and twisting motions of the
      hydrogen atoms. From the atomic contribution patterns (ACPs) and the group
      coupling matrices (GCMs), one finds that the VROA backward-scattering intensities
      mainly arise from hydrogen and carbon atoms in the vicinity of the two chiral
      nitrogen atoms. The VROA signatures in the 1140-1400 cm(-1) range are therefore a
      fingerprint of the local chirality around the two chiral nitrogen centers.

PMID- 21967046
TI  - Validation of the extended ICF core set for stroke from the patient perspective
      using focus groups.
AB  - PURPOSE: The extended international classification of functioning, disability and
      health (ICF) core set for stroke is an application of the ICF of the World Health
      Organisation (WHO) with the purpose to represent the typical spectrum of
      functioning of persons with stroke. The objective of the study was to add
      evidence to the validation of the extended ICF core set for stroke from the
      perspective of patients using focus groups to explore the aspects of functioning
      and health important to persons with stroke. METHOD: The sampling of patients
      followed the maximum variation strategy. Sample size was determined by
      saturation. The focus groups were digitally recorded and transcribed verbatim.
      After qualitative data analysis, the resulting concepts were linked to ICF
      categories and compared to the categories included in the extended ICF core set
      for stroke. RESULTS: Sixty patients participated in 15 focus groups. The content
      of 131 out of 166 ICF categories contained in the extended ICF core set for
      stroke was reported by the persons with stroke. The content of 31 additional
      categories that are not covered in the extended ICF core set for stroke was
      raised. CONCLUSIONS: The existing version of the extended ICF core set for stroke
      could be confirmed almost entirely from patient perspective.

PMID- 21967047
TI  - Breastfeeding: a clinical imperative.
AB  - Hospital breastfeeding initiation rates (75%) show that most mothers in the
      United States want to breastfeed and are trying to do so. Even from the very
      start, however, mothers may not be getting the breastfeeding support they need.
      Low breastfeeding rates at 3, 6, and 12 months illustrate that women face
      multiple additional barriers to maintaining breastfeeding. What can we do to help
      more mothers be more successful? As healthcare providers, we need to be believers
      that breastfeeding is worth the effort. Perhaps most important for us is to
      realize that human milk is not simply a food but rather a complex, human infant
      support system. We can then articulate to families the importance of
      breastfeeding as a clinical imperative, a preventer of acute and chronic illness
      and disease. It will take integration, normalization, and mainstreaming of
      breastfeeding into our culture for acceptance and growth of the practice. Once we
      assist families in making educated decisions about breastfeeding, we need to
      provide supportive environments in our hospitals, medical practices, workplaces,
      and communities that implement the best ways to support breastfeeding. Breast
      milk is worth the effort, and the time has come to be ardent supporters of
      mothers and infants and their breastfeeding intentions.

PMID- 21967048
TI  - Evidence-based evaluation and management of chronic urticaria in children.
AB  - Urticaria affects nearly 25% of the population at some time in their lives. In a
      subset of children, urticaria will develop into a chronic condition that can
      greatly affect quality of life. Although numerous causes and triggers are
      proposed for chronic urticaria (CU) in children, ranging from infections,
      allergens, and medications to physical factors and autoimmune disease, the exact
      etiology is not always identifiable. Accordingly, a large subset of cases are
      designated "chronic idiopathic urticaria." Because of the clinical complexities
      of CU, as well as the confusing literature on this topic, we have developed a
      conceptual framework based on the cumulative evidence to assist with the
      categorization, clinical evaluation, and treatment of CU in children.

PMID- 21967049
TI  - ABC transporters, mechanisms and biology: an overview.
AB  - This chapter concentrates mainly on structural and mechanistic aspects of ABC
      (ATP-binding cassette) transporters and, as an example of the physiological
      significance of these proteins, on lipid transport, vitally important for human
      health. The chapter considers those aspects of ABC transporter function that
      appear reasonably well established, those that remain controversial and what
      appear to be emerging themes. Although we have seen dramatic progress in ABC
      protein studies in the last 20 years, we are still far from a detailed molecular
      understanding of function. Nevertheless two critical steps - capture and release
      of allocrites (transport substrates) involving a binding cavity in the membrane
      domain, and hydrolysis of ATP by the NBD (nucleotide-binding domain) dimer - are
      now described by persuasive and testable models: alternating access, and
      sequential firing of catalysis sites respectively. However, these need to be
      tested rigorously by more structural and biochemical studies. Other aspects
      considered include the level at which ATP binding and dimer activation are
      controlled, the nature of the power stroke delivering mechanical energy for
      transport, and some unexpected and intriguing differences between importers and
      exporters. The chapter also emphasizes that some ABC transporters, although
      important for elimination of toxic compounds (xenobiotics), are also increasingly
      seen to play crucial roles in homoeostatic regulation of membrane biogenesis and
      function through translocation of endogenous allocrites such as cholesterol.
      Another emerging theme is the identification of accessory domains and partners
      for ABC proteins, resulting in a corresponding widening of the range of
      activities. Finally, what are the prospects for translational research and ABC
      transporters?

PMID- 21967050
TI  - Natural history of ABC systems: not only transporters.
AB  - In recent years, our understanding of the functioning of ABC (ATP-binding
      cassette) systems has been boosted by the combination of biochemical and
      structural approaches. However, the origin and the distribution of ABC proteins
      among living organisms are difficult to understand in a phylogenetic perspective,
      because it is hard to discriminate orthology and paralogy, due to the existence
      of horizontal gene transfer. In this chapter, I present an update of the
      classification of ABC systems and discuss a hypothetical scenario of their
      evolution. The hypothetical presence of ABC ATPases in the last common ancestor
      of modern organisms is discussed, as well as the additional possibility that ABC
      systems might have been transmitted to eukaryotes, after the two endosymbiosis
      events that led to the constitution of eukaryotic organelles. I update the
      functional information of selected ABC systems and introduce new families of ABC
      proteins that have been included recently into this vast superfamily, thanks to
      the availability of high-resolution three-dimensional structures.

PMID- 21967051
TI  - Structure of ABC transporters.
AB  - ABC (ATP-binding cassette) transporters are primary active membrane proteins that
      translocate solutes (allocrites) across lipid bilayers. The prototypical ABC
      transporter consists of four domains: two cytoplasmic NBDs (nucleotide-binding
      domains) and two TMDs (transmembrane domains). The NBDs, whose primary sequence
      is highly conserved throughout the superfamily, bind and hydrolyse ATP to power
      the transport cycle. The TMDs, whose primary sequence and protein fold can be
      quite disparate, form the translocation pathway across the membrane and generally
      (but not always) determine allocrite specificity. Structure determination of ABC
      proteins initially took advantage of the relative ease of expression and
      crystallization of the hydrophilic bacterial NBDs in isolation from the
      transporter complex, and revealed detailed information on the structural fold of
      these domains, the amino acids involved in the binding and hydrolysis of
      nucleotide, and the head-to-tail arrangement of the NBD-NBD dimer interface. More
      recently, several intact transporters have been crystallized and three types
      have, so far, been characterized: type I and II ABC importers, and ABC exporters.
      All three are present in prokaryotes, but only the ABC exporters appear to be
      present in eukaryotes. Their structural determination has provided insight into
      the mechanisms of energy and signal transduction between the NBDs and TMDs (i.e.
      between the ATP- and allocrite-binding sites) and, for some, the nature of the
      allocrite-binding site(s) within the TMDs. In this chapter, we focus primarily on
      the ABC exporters and describe the structural, biochemical and biophysical
      evidence for and against the controversial bellows-like mechanism proposed for
      allocrite efflux.

PMID- 21967052
TI  - Catalytic and transport cycles of ABC exporters.
AB  - ABC (ATP-binding cassette) transporters are arguably the most important family of
      ATP-driven transporters in biology. Despite considerable effort and advances in
      determining the structures and physiology of these transporters, their
      fundamental molecular mechanisms remain elusive and highly controversial. How
      does ATP hydrolysis by ABC transporters drive their transport function? Part of
      the problem in answering this question appears to be a perceived need to
      formulate a universal mechanism. Although it has been generally hoped and assumed
      that the whole superfamily of ABC transporters would exhibit similar conserved
      mechanisms, this is proving not to be the case. Structural considerations alone
      suggest that there are three overall types of coupling mechanisms related to ABC
      exporters, small ABC importers and large ABC importers. Biochemical and
      biophysical characterization leads us to the conclusion that, even within these
      three classes, the catalytic and transport mechanisms are not fully conserved,
      but continue to evolve. ABC transporters also exhibit unusual characteristics not
      observed in other primary transporters, such as uncoupled basal ATPase activity,
      that severely complicate mechanistic studies by established methods. In this
      chapter, I review these issues as related to ABC exporters in particular. A
      consensus view has emerged that ABC exporters follow alternating-access switch
      transport mechanisms. However, some biochemical data suggest that alternating
      catalytic site transport mechanisms are more appropriate for fully symmetrical
      ABC exporters. Heterodimeric and asymmetrical ABC exporters appear to conform to
      simple alternating-access-type mechanisms.

PMID- 21967053
TI  - ABC solute importers in bacteria.
AB  - The bacterial ABC (ATP-binding cassette) importers mediate nutrient uptake and
      some are essential for survival in environments where nutrients are limited, such
      as in the human body. Although ABC importers exhibit remarkable versatility in
      the substrates that they can transport, they appear to share a similar
      multisubunit architecture and mechanism of energization by ATP hydrolysis. This
      chapter will provide both basic understanding and up-to-date information on the
      structure, mechanism and regulation of this important family of proteins.

PMID- 21967054
TI  - ABC proteins in yeast and fungal pathogens.
AB  - All fungal genomes harbour numerous ABC (ATP-binding cassette) proteins located
      in various cellular compartments such as the plasma membrane, vacuoles,
      peroxisomes and mitochondria. Most of them have initially been discovered through
      their ability to confer resistance to a multitude of drugs, a phenomenon called
      PDR (pleiotropic drug resistance) or MDR (multidrug resistance). Studying the
      mechanisms underlying PDR/MDR in yeast is of importance in two ways: first, ABC
      proteins can confer drug resistance on pathogenic fungi such as Candida spp.,
      Aspergillus spp. or Cryptococcus neoformans; secondly, the well-established
      genetic, biochemical and cell biological tractability of Saccharomyces cerevisiae
      makes it an ideal tool to study basic mechanisms of drug transport by ABC
      proteins. In the past, knowledge from yeast has complemented work on human ABC
      transporters involved in anticancer drug resistance or genetic diseases.
      Interestingly, increasing evidence available from yeast and other organisms
      suggests that ABC proteins play a physiological role in membrane homoeostasis and
      lipid distribution, although this is being intensely debated in the literature.

PMID- 21967055
TI  - ABC transporters involved in drug resistance in human parasites.
AB  - The ABC (ATP-binding cassette) protein superfamily is a ubiquitous and
      functionally versatile family of proteins that is conserved from archaea to
      humans. In eukaryotes, most of these proteins are implicated in the transport of
      a variety of molecules across cellular membranes, whereas the remaining ones are
      involved in biological processes unrelated to transport. The biological functions
      of several ABC proteins have been described in clinically important parasites and
      nematode worms and include vesicular trafficking, phospholipid movement,
      translation and drug resistance. This chapter reviews our current understanding
      of the role of ABC proteins in drug resistance and treatment failure in
      apicomplexan, trypanosomatid and amitochondriate parasites of medical relevance
      as well as in helminths.

PMID- 21967056
TI  - Functions of ABC transporters in plants.
AB  - ABC (ATP-binding cassette) proteins are ubiquitously found in prokaryotes and
      eukaryotes and generally serve as membrane-intrinsic primary active pumps. In
      higher plants, ABC proteins constitute a large family, grouped phylogenetically
      into eight clusters, subfamilies ABCA-ABCI (ABCH is not found in plants). ABC
      transporters shuttle substrates as diverse as lipids, phytohormones,
      carboxylates, heavy metals, chlorophyll catabolites and xenobiotic conjugates
      across a variety of biological membranes. To date, the largest proportions of
      characterized members have been localized to the plasma membrane and the
      tonoplast, with dominant implications in cellular secretion and vacuolar
      sequestration, but they are also found in mitochondrial, plastidal and
      peroxisomal membranes. Originally identified as tonoplast-intrinsic proteins that
      shuttle xenobiotic conjugates from the cytosol into the vacuole, thus being an
      integral part of the detoxification machinery, ABC transporters are now
      recognized to participate in a multitude of physiological processes that allow
      the plant to adapt to changing environments and cope with biotic and abiotic
      stresses.

PMID- 21967057
TI  - The P-glycoprotein multidrug transporter.
AB  - Pgp (P-glycoprotein) (ABCB1) is an ATP-powered efflux pump which can transport
      hundreds of structurally unrelated hydrophobic amphipathic compounds, including
      therapeutic drugs, peptides and lipid-like compounds. This 170 kDa polypeptide
      plays a crucial physiological role in protecting tissues from toxic xenobiotics
      and endogenous metabolites, and also affects the uptake and distribution of many
      clinically important drugs. It forms a major component of the blood-brain barrier
      and restricts the uptake of drugs from the intestine. The protein is also
      expressed in many human cancers, where it probably contributes to resistance to
      chemotherapy treatment. Many chemical modulators have been identified that block
      the action of Pgp, and may have clinical applications in improving drug delivery
      and treating cancer. Pgp substrates are generally lipid-soluble, and partition
      into the membrane before the transporter expels them into the aqueous phase, much
      like a 'hydrophobic vacuum cleaner'. The transporter may also act as a
      'flippase', moving its substrates from the inner to the outer membrane leaflet.
      An X-ray crystal structure shows that drugs interact with Pgp within the
      transmembrane regions by fitting into a large flexible binding pocket, which can
      accommodate several substrate molecules simultaneously. The nucleotide-binding
      domains of Pgp appear to hydrolyse ATP in an alternating manner; however, it is
      still not clear whether transport is driven by ATP hydrolysis or ATP binding.
      Details of the steps involved in the drug-transport process, and how it is
      coupled to ATP hydrolysis, remain the object of intensive study.

PMID- 21967058
TI  - Mammalian multidrug-resistance proteins (MRPs).
AB  - Subfamily C of the human ABC (ATP-binding cassette) superfamily contains nine
      proteins that are often referred to as the MRPs (multidrug-resistance proteins).
      The 'short' MRP/ABCC transporters (MRP4, MRP5, MRP8 and ABCC12) have a typical
      ABC structure with four domains comprising two membrane-spanning domains (MSD1
      and MSD2) each followed by a nucleotide-binding domain (NBD1 and NBD2). The
      'long' MRP/ABCCs (MRP1, MRP2, MRP3, ABCC6 and MRP7) have five domains with the
      extra domain, MSD0, at the N-terminus. The proteins encoded by the ABCC6 and
      ABCC12 genes are not known to transport drugs and are therefore referred to as
      ABCC6 and ABCC12 (rather than MRP6 and MRP9) respectively. A large number of
      molecules are transported across the plasma membrane by the MRPs. Many are
      organic anions derived from exogenous sources such as conjugated drug
      metabolites. Others are endogenous metabolites such as the cysteinyl leukotrienes
      and prostaglandins which have important signalling functions in the cell. Some
      MRPs share a degree of overlap in substrate specificity (at least in vitro), but
      differences in transport kinetics are often substantial. In some cases, the in
      vivo substrates for some MRPs have been discovered aided by studies in gene
      knockout mice. However, the molecules that are transported in vivo by others,
      including MRP5, MRP7, ABCC6 and ABCC12, still remain unknown. Important
      differences in the tissue distribution of the MRPs and their membrane
      localization (apical in contrast with basolateral) in polarized cells also exist.
      Together, these differences are responsible for the unique pharmacological and
      physiological functions of each of the nine ABCC transporters known as the MRPs.

PMID- 21967059
TI  - The controversial role of ABC transporters in clinical oncology.
AB  - The phenomenon of multidrug resistance in cancer is often associated with the
      overexpression of the ABC (ATP-binding cassette) transporters Pgp (P
      glycoprotein) (ABCB1), MRP1 (multidrug resistance-associated protein 1) (ABCC1)
      and ABCG2 [BCRP (breast cancer resistance protein)]. Since the discovery of Pgp
      over 35 years ago, studies have convincingly linked ABC transporter expression to
      poor outcome in several cancer types, leading to the development of transporter
      inhibitors. Three generations of inhibitors later, we are still no closer to
      validating the 'Pgp hypothesis', the idea that increased chemotherapy efficacy
      can be achieved by inhibition of transporter-mediated efflux. In this chapter, we
      highlight the difficulties and past failures encountered in the development of
      clinical inhibitors of ABC transporters. We discuss the challenges that remain in
      our effort to exploit decades of work on ABC transporters in oncology. In
      learning from past mistakes, it is hoped that ABC transporters can be developed
      as targets for clinical intervention.

PMID- 21967060
TI  - Insights into the mechanisms underlying CFTR channel activity, the molecular
      basis for cystic fibrosis and strategies for therapy.
AB  - Mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) cause
      CF (cystic fibrosis), a fatal genetic disease commonly leading to airway
      obstruction with recurrent airway inflammation and infection. Pulmonary
      obstruction in CF has been linked to the loss of CFTR function as a regulated Cl-
      channel on the lumen-facing membrane of the epithelium lining the airways. We
      have learned much about the molecular basis for nucleotide- and phosphorylation
      dependent regulation of channel activity of the normal (wild-type) version of the
      CFTR protein through electrophysiological studies. The major CF-causing mutation,
      F508del-CFTR, causes the protein to misfold and be retained in the ER
      (endoplasmic reticulum). Importantly, recent studies in cell culture have shown
      that retention in the ER can be 'corrected' through the application of certain
      small-molecule modulators and, once at the surface, the altered channel function
      of the major mutant can be 'potentiated', pharmacologically. Importantly, two
      such small molecules, a 'corrector' (VX-809) and a 'potentiator' (VX-770)
      compound are undergoing clinical trial for the treatment of CF. In this chapter,
      we describe recent discoveries regarding the wild-type CFTR and F508del-CFTR
      protein, in the context of molecular models based on X-ray structures of
      prokaryotic ABC (ATP-binding cassette) proteins. Finally, we discuss the promise
      of small-molecule modulators to probe the relationship between structure and
      function in the wild-type protein, the molecular defects caused by the most
      common mutation and the structural changes required to correct these defects.

PMID- 21967061
TI  - The TAP translocation machinery in adaptive immunity and viral escape mechanisms.
AB  - The adaptive immune system plays an essential role in protecting vertebrates
      against a broad range of pathogens and cancer. The MHC class I-dependent pathway
      of antigen presentation represents a sophisticated cellular machinery to
      recognize and eliminate infected or malignantly transformed cells, taking
      advantage of the proteasomal turnover of the cell's proteome. TAP (transporter
      associated with antigen processing) 1/2 (ABCB2/3, where ABC is ATP-binding
      cassette) is the principal component in the recognition, translocation,
      chaperoning, editing and final loading of antigenic peptides on to MHC I
      complexes in the ER (endoplasmic reticulum) lumen. These different tasks are co
      ordinated within a dynamic macromolecular peptide-loading complex consisting of
      TAP1/2 and various auxiliary factors, such as the adapter protein tapasin, the
      oxidoreductase ERp57, the lectin chaperone calreticulin, and the final peptide
      acceptor the MHC I heavy chain associated with beta2-microglobulin. In this
      chapter, we summarize the structural organization and molecular mechanism of the
      antigen-translocation machinery as well as various modes of regulation by viral
      factors and in genetic diseases and tumour development.

PMID- 21967062
TI  - Lipid transport by mammalian ABC proteins.
AB  - ABC (ATP-binding cassette) proteins actively transport a wide variety of
      substrates, including peptides, amino acids, sugars, metals, drugs, vitamins and
      lipids, across extracellular and intracellular membranes. Of the 49 hum an ABC
      proteins, a significant number are known to mediate the extrusion of lipids from
      membranes or the flipping of membrane lipids across the bilayer to generate and
      maintain membrane lipid asymmetry. Typical lipid substrates include
      phospholipids, sterols, sphingolipids, bile acids and related lipid conjugates.
      Members of the ABCA subfamily of ABC transporters and other ABC proteins such as
      ABCB4, ABCG1 and ABCG5/8 implicated in lipid transport play important roles in
      diverse biological processes such as cell signalling, membrane lipid asymmetry,
      removal of potentially toxic compounds and metabolites, and apoptosis. The
      importance of these ABC lipid transporters in cell physiology is evident from the
      finding that mutations in the genes encoding many of these proteins are
      responsible for severe inherited diseases. For example, mutations in ABCA1 cause
      Tangier disease associated with defective efflux of cholesterol and
      phosphatidylcholine from the plasma membrane to the lipid acceptor protein apoA1
      (apolipoprotein AI), mutations in ABCA3 cause neonatal surfactant deficiency
      associated with a loss in secretion of the lipid pulmonary surfactants from lungs
      of newborns, mutations in ABCA4 cause Stargardt macular degeneration, a retinal
      degenerative disease linked to the reduced clearance of retinoid compounds from
      photoreceptor cells, mutations in ABCA12 cause harlequin and lamellar ichthyosis,
      skin diseases associated with defective lipid trafficking in keratinocytes, and
      mutations in ABCB4 and ABCG5/ABCG8 are responsible for progressive intrafamilial
      hepatic disease and sitosterolaemia associated with defective phospholipid and
      sterol transport respectively. This chapter highlights the involvement of various
      mammalian ABC transporters in lipid transport in the context of their role in
      cell signalling, cellular homoeostasis, apoptosis and inherited disorders.

PMID- 21967063
TI  - Enhanced free exciton and direct band-edge emissions at room temperature in
      ultrathin ZnO films grown on Si nanopillars by atomic layer deposition.
AB  - Room-temperature ultraviolet (UV) luminescence was investigated for the atomic
      layer deposited ZnO films grown on silicon nanopillars (Si-NPs) fabricated by
      self-masking dry etching in hydrogen-containing plasma. For films deposited at
      200  degrees C, an intensive UV emission corresponding to free-exciton
      recombination (~3.31 eV) was observed with a nearly complete suppression of the
      defect-associated broad visible range emission peak. On the other hand, for ZnO
      films grown at 25  degrees C, albeit the appearance of the defect-associated
      visible emission, the UV emission peak was observed to shift by ~60 meV to near
      the direct band edge (3.37 eV) recombination emission. The high-resolution
      transmission electron microscopy (HRTEM) showed that the ZnO films obtained at 25
      degrees C were consisting of ZnO nanocrystals with a mean radius of 2 nm
      embedded in a largely amorphous matrix. Because the Bohr radius of free-exictons
      in bulk ZnO is ~2.3 nm, the size confinement effect may have occurred and
      resulted in the observed direct band edge electron-hole recombination.
      Additionally, the results also demonstrate order of magnitude enhancement in
      emission efficiency for the ZnO/Si-NP structure, as compared to that of ZnO
      directly deposited on Si substrate under the same conditions.

PMID- 21967064
TI  - Unexpected controllable pair-structure in ferroelectric nanodomains.
AB  - The imminent inability of silicon-based memory devices to satisfy Moore's Law is
      approaching rapidly. Controllable nanodomains of ferroic systems are anticipated
      to enable future high-density nonvolatile memory and novel electronic devices. We
      find via piezoresponse force microscopy (PFM) studies on lead zirconate titanate
      (PZT) films an unexpected nanostructuring of ferroelectric-ferroelastic domains.
      These consist of c-nanodomains within a-nanodomains in proximity to a-nanodomains
      within c-domains. These structures are created and annihilated as pairs,
      controllably. We treat these as a new kind of vertex-antivertex pair and consider
      them in terms of the Srolovitz-Scott 4-state Potts model, which results in
      pairwise domain vertex instabilities that resemble the vortex-antivortex
      mechanism in ferromagnetism, as well as dislocation pairs (or disclination pairs)
      that are well-known in nematic liquid crystals. Finally, we show that these
      nanopairs can be scaled up to form arrays that are engineered at will, paving the
      way toward facilitating them to real technologies.

PMID- 21967065
TI  - Smart nanocarrier based on PEGylated hyaluronic acid for cancer therapy.
AB  - Tumor targetability and site-specific drug release of therapeutic nanoparticles
      are key factors for effective cancer therapy. In this study, poly(ethylene
      glycol) (PEG)-conjugated hyaluronic acid nanoparticles (P-HA-NPs) were
      investigated as carriers for anticancer drugs including doxorubicin and
      camptothecin (CPT). P-HA-NPs were internalized into cancer cells (SCC7 and MDA-MB
      231) via receptor-mediated endocytosis, but were rarely taken up by normal
      fibroblasts (NIH-3T3). During in vitro drug release tests, P-HA-NPs rapidly
      released drugs when incubated with cancer cells, extracts of tumor tissues, or
      the enzyme Hyal-1, which is abundant in the intracellular compartments of cancer
      cells. CPT-loaded P-HA-NPs (CPT-P-HA-NPs) showed dose-dependent cytotoxicity to
      cancer cells (MDA-MB-231, SCC7, and HCT 116) and significantly lower cytotoxicity
      against normal fibroblasts (NIH-3T3) than free CPT. Unexpectedly, high
      concentrations of CPT-P-HA-NPs demonstrated greater cytotoxicity to cancer cells
      than free CPT. An in vivo biodistribution study indicated that P-HA-NPs
      selectively accumulated into tumor sites after systemic administration into tumor
      bearing mice, primarily due to prolonged circulation in the blood and binding to
      a receptor (CD44) that was overexpressed on the cancer cells. In addition, when
      CPT-P-HA-NPs were systemically administrated into tumor-bearing mice, we saw no
      significant increases in tumor size for at least 35 days, implying high antitumor
      activity. Overall, P-HA-NPs showed promising potential as a drug carrier for
      cancer therapy.

PMID- 21967066
TI  - What's New, What's Hot in Solid Organ Transplantation? Summary of the American
      Transplant Congress 2011.
AB  - Breakthroughs in basic and clinical science in solid organ transplantation were
      presented at the American Transplant Congress 2011. Key areas of presentation
      included the pathogenesis of late allograft failure, immune regulation and
      tolerance, pathways in allograft injury, electing appropriate patients for
      transplantation, determining the best allocation schemes to maximize effective
      utilization, organ preservation, monitoring the alloimmune response and
      immunosuppressive management. In this review, we present highlights of the
      meeting. These presentations demonstrate the exciting promise in translating from
      the bench to affect patient care.

PMID- 21967067
TI  - Laser thermal therapy of benign skin tumours: review and update.
AB  - The goal of this review is to provide an overview on laser treatment of benign
      skin tumours and recent developments in this field. Ablational laser systems are
      established treatment devices for benign skin tumours. They obtain good cosmetic
      results with mostly minimal side-effects. Recently, fractional laser devices or
      combination of laser therapy with photodynamic therapy has gained attention in
      this field. However, there is a lack of randomised, controlled trials for laser
      treatment of benign skin tumours.

PMID- 21967068
TI  - Primary ocular herpes simplex virus infection with zosteriform spreading,
      accompanied with meningism.

PMID- 21967069
TI  - Long-term assessment of topiramate for epilepsy: an open-label, single-arm,
      multicentre, prospective study in a naturalistic setting.
AB  - BACKGROUND AND OBJECTIVE: Most patients with epilepsy require long-term medical
      therapy. Newer antiepileptic drugs (AEDs) appear to be overall similarly
      effective to older agents but may be better tolerated. However, most of the
      clinical data available for newer AEDs derive from a number of short-term
      studies. The objective of this study was to explore long-term outcomes in
      patients with epilepsy treated with topiramate in routine clinical practice.
      METHODS: This was an open-label, multicentre, optional follow-up monotherapy
      study that included adolescents and adults with epilepsy who completed two
      similarly designed 28- or 30-week studies and agreed to participate for an
      additional 52 weeks. Seizure types and frequency, topiramate dose, vital signs
      and treatment-emergent adverse events (TEAEs) after 12, 26, 39 and 52 weeks were
      documented. Post hoc analyses to explore differences between males and females
      were conducted. RESULTS: 114 patients (49.0% women, mean +/- SD age 43 +/- 17.5
      years) with a mean +/- SD disease duration of 61 +/- 118 months (men 54 +/- 96 vs
      women 68 +/- 138 months) were followed up for a median of 18.5 months. Seventy
      eight percent of patients completed the study. Reasons for premature
      discontinuation were: loss to follow-up (10.5%), TEAE (5.3%), lack of efficacy
      (2.6%), non-adherence (0.9%) and other reasons (4.4%). Seizure frequency per 4
      weeks decreased from a mean +/- SD 5.0 +/- 28.3 at baseline to 0.6 +/- 2.1 during
      the whole observation period. Fifty-four patients (52.9%) were seizure free
      during the whole observation period. In addition, 69 of 95 patients (72.6%) whose
      topiramate therapy was stable within a range of +/-50 mg/day for a period of at
      least 12 months (maintenance phase) were seizure free while treated with a median
      topiramate dose of 100 mg/day. The most frequently reported TEAEs were
      paraesthesias (13.2% of patients), dizziness (7.0%) and seizure-related events
      (7.0%). No significant differences between males and females were found for
      treatment response or retention. CONCLUSION: Topiramate is an effective and well
      tolerated long-term treatment option for adolescents and adults with epilepsy.

PMID- 21967070
TI  - Determining clinically important changes in range of motion in patients with
      Dupuytren's Contracture: secondary analysis of the randomized, double-blind,
      placebo-controlled CORD I study.
AB  - BACKGROUND AND OBJECTIVE: Injectable collagenase Clostridium histolyticum is
      efficacious in correcting Dupuytren's contracture as assessed by changes in the
      angle of contracture and range of motion (ROM). However, clinically important
      changes in ROM have not been evaluated in depth. The objective of this secondary
      analysis of the CORD I trial was to identify severity levels using baseline ROM,
      estimate a clinically important difference (CID) for ROM, and link the results to
      collagenase treatment and patient satisfaction. METHODS: In the CORD I trial,
      patients with Dupuytren's disease and joint contractures >=20 degrees  were
      randomized to receive a maximum of three collagenase 0.58 mg or placebo
      injections into the cord of the affected hand at 30-day intervals. The primary
      endpoint was reduction in contracture to <=5 degrees  30 days after the last
      injection (day 30). The secondary endpoints, which are reported in this analysis,
      were ROM, physician- and patient-rated severity ('normal', 'mild', 'moderate',
      'severe') and improvement, and treatment satisfaction. Linear regression was used
      to model data for severity classification and CID estimation for ROM based on
      physician and patient ratings. RESULTS: At baseline, mean ROM was 43.9 degrees 
      in the collagenase-treated joints (n = 197) and 45.3 degrees  in the placebo
      treated joints (n = 102). On day 30, mean ROM was 80.7 degrees  in the
      collagenase-treated joints and 49.5 degrees  in the placebo-treated joints. The
      mean increase in ROM was 36.7 degrees  in the collagenase-treated joints (p <
      0.001) and 4.0 degrees  in the placebo-treated joints (not significant). The
      estimated CID for ROM was 13.5 degrees  (95% CI 11.9, 15.1), reflecting a one
      category change in severity. The mean increase in ROM exceeded the CID in the
      collagenase-treated joints but not in the placebo-treated joints; the difference
      between collagenase treatment and placebo in the mean increase in ROM also
      exceeded the CID, implying that the improvement with collagenase was clinically
      relevant. The severity classification for ROM was: >=67.0 degrees  ('normal'),
      >=54.3 and <67.0 degrees  ('mild'), >=41.6 and <54.3 degrees  ('moderate'), and
      <41.6 degrees  ('severe'). More collagenase- than placebo-treated patients
      achieved 'normal' (81% vs 25%; p < 0.0001) status, and more collagenase- than
      placebo-treated patients reported being 'very/quite satisfied' (87% vs 32%; p <
      0.001). CONCLUSION: Injectable collagenase significantly improves ROM and
      treatment satisfaction versus placebo. ROM improvements are clinically relevant
      as well as statistically significant. These data support the potential need to
      include ROM and physician- and patient-rated severity and satisfaction as
      standard assessments for Dupuytren's contracture treatment outcomes. TRIAL
      REGISTRATION: ClinicalTrials.gov Identifier: NCT00528606; other study
      identification number: AUX-CC-857 (Auxilium Pharmaceuticals, Inc.).

PMID- 21967072
TI  - Therapeutic alliance and family-based treatment for adolescents with anorexia
      nervosa.
AB  - This pilot study examines the role of therapeutic alliance in relation to weight
      gain and change in psychological measures during family-based treatment for
      adolescent anorexia nervosa (AN). Our sample consisted of 14 adolescents with AN
      and their families. Therapeutic alliance was measured using the System for
      Observing Family Therapy Alliances Scale. Those adolescents who attained at least
      85% of their ideal body weight at the end of treatment had parents who showed a
      stronger therapeutic alliance with the therapist during the second session of
      treatment, while adolescents who were remitted on psychological measures showed a
      higher therapeutic alliance between themselves and the therapist early in
      treatment. It appears that therapeutic alliance plays an important role in
      outcome in family-based treatment for AN. Further study is needed in this area to
      explore the role of the therapist in creating and maintaining a strong
      therapeutic alliance.

PMID- 21967071
TI  - Effect of nalmefene 20 and 80 mg on the corrected QT interval and T-wave
      morphology: a randomized, double-blind, parallel-group, placebo- and moxifloxacin
      controlled, single-centre study.
AB  - BACKGROUND: Nalmefene is an orally administered competitive opioid receptor
      antagonist targeted at reducing alcohol consumption in alcohol-dependent
      patients. As part of the regulatory requirements for drug approval, the potential
      of novel compounds for causing unwanted proarrhythmia should be studied in a
      thoroughly designed clinical QT/corrected QT (QTc) study (International
      Conference on Harmonisation [ICH] E14 guideline). OBJECTIVE: This study was
      designed to evaluate whether nalmefene 20 and 80 mg/day induced changes in
      cardiac repolarization biomarkers indicative of proarrhythmia (the QTc interval
      and T-wave morphology). METHODS: This was a prospective, randomized, double
      blind, parallel-group, placebo- and moxifloxacin-controlled, single-centre study
      carried out in a clinical pharmacology unit. The study included 270 healthy male
      and female subjects (age 18-45 years). The subjects were randomized to a 7-day
      treatment period of placebo, nalmefene 20 mg/day or nalmefene 80 mg/day, or
      placebo for 6 days followed by a single dose of moxifloxacin 400 mg on day 7.
      Serial triplicate ECGs were obtained over a 24-hour period at protocol-defined
      time-points. The primary protocol-defined endpoint was the largest time-matched
      baseline- and placebo-adjusted mean difference in the individually heart rate
      corrected QT interval (QTcNi) recorded at any of the 12 ECG time-points
      distributed over a 24-hour period on day 7 of treatment. Secondary endpoints
      included a similar analysis using the Fridericia- (QTcF) and Bazett-corrected
      (QTcB) intervals. An explorative analysis included quantitative assessment of T
      wave morphology using the T-wave morphology composite score (MCS) to assess for
      differences between treatment groups and placebo on day 7 of treatment. The
      frequency of outliers in the QTc intervals, the pharmacokinetics of nalmefene and
      the tolerability of nalmefene were also assessed. RESULTS: Nalmefene was rapidly
      absorbed with a time to reach maximum plasma concentration of 2.2 hours and a
      dose-proportionate relationship between dose administered and exposure. The
      largest baseline- and placebo-adjusted mean changes from baseline in the
      individualized QTcNi (primary endpoint) were 5.45 ms (90% CI 1.52, 9.37) and 5.57
      ms (90% CI 1.62, 9.52) for nalmefene 20 and 80 mg/day, respectively, with study
      sensitivity confirmed by the expected largest increase in mean QTcNi of 10.15 ms
      (90% CI 5.67, 14.63) for moxifloxacin. Quantitative assessment using the T-wave
      MCS demonstrated the largest baseline- and placebo-adjusted increase in MCS to be
      non-significantly different from the intra-subject variability of triplicate
      recordings in the placebo group. No deaths or serious adverse events occurred in
      the study. CONCLUSION: This thorough QT/QTc study was a negative study in
      accordance with the ICH E14 guideline, meaning that nalmefene has no clinically
      relevant effect on the QTc interval and T-wave morphology. The study predicts no
      concern over proarrhythmia or need for intensive QTc monitoring with the use of
      nalmefene in clinical practice.

PMID- 21967073
TI  - Outcome expectancy as a predictor of treatment response in cognitive behavioral
      therapy for public speaking fears within social anxiety disorder.
AB  - Outcome expectancy, the extent that clients anticipate benefiting from therapy,
      is theorized to be an important predictor of treatment response for cognitive
      behavioral therapy. However, there is a relatively small body of empirical
      research on outcome expectancy and the treatment of social anxiety disorder. This
      literature, which has examined the association mostly in group-based
      interventions, has yielded mixed findings. The current study sought to further
      evaluate the effect of outcome expectancy as a predictor of treatment response
      for public-speaking fears across both individual virtual reality and group-based
      cognitive-behavioral therapies. The findings supported outcome expectancy as a
      predictor of the rate of change in public-speaking anxiety during both individual
      virtual reality exposure therapy and group cognitive-behavioral therapy.
      Furthermore, there was no evidence to suggest that the impact of outcome
      expectancy differed across virtual reality or group treatments.

PMID- 21967074
TI  - Exploring corrective experiences in a successful case of short-term dynamic
      psychotherapy.
AB  - The concept of corrective emotional experience, originally formulated by
      psychoanalysts Alexander and French (1946), has been redefined by contemporary
      researchers to be theoretically nonspecific, that is, as "coming to understand or
      experience an event or relationship in a different or unexpected way" (Castonguay
      & Hill, 2011). Using postsession questionnaires, videotapes, and posttermination
      interviews, we explored whether (and how) a corrective experience occurred in a
      successful case of short-term dynamic psychotherapy (STDP; Davanloo, 1980). A 35
      year-old woman suffering severe panic attacks was seen for 31 sessions by an
      experienced STDP therapist. The questionnaires and interviews focused on (a)
      perceived intrapsychic and interpersonal changes, and (b) how these changes came
      about. At termination, the client reported complete symptom relief, greater self
      acceptance, improved relationships, and more emotional flexibility. Her
      corrective experience was evident in the qualitative themes, which showed that
      she came to understand and affectively experience her relationships with both
      parents differently. Moreover, the themes reflected both STDP-specific (e.g.,
      confrontation of defenses) and nonspecific (e.g., rapport, acceptance) mechanisms
      of change. Conversation analysis (Sacks, 1995) of what the client described as
      "the 'gentle shove' of questions that make me see what I have been trying to
      ignore since childhood" showed, on a microlinguistic level, how she overcame
      resistance to strong emotional experience and expression.

PMID- 21967075
TI  - Bringing the psychotherapist back: basic concepts for reading articles examining
      therapist effects using multilevel modeling.
AB  - Psychotherapy research examining the influence of psychotherapists on clients'
      clinical outcomes can provide valuable insights for enhancing psychotherapists'
      effectiveness. Psychotherapy data often have a hierarchical structure--multiple
      clients treated by the same psychotherapist. As such, researchers are more
      commonly turning to the use of advanced statistical methods, namely multilevel
      modeling (MLM), to address this complexity. In this article, we describe MLM for
      consumers of psychotherapy studies so they can better understand and evaluate
      studies that employ this method. We provide an example study that illustrates how
      traditional statistical methods may conceal meaningful findings. Also, we
      describe commonly utilized applications of MLM in psychotherapy research, such as
      variation among psychotherapist effects in outcomes, variation in the
      relationship between predictors and outcomes that can be attributed to
      psychotherapists, and sample size concerns.

PMID- 21967076
TI  - Vitamin D deficiency and rickets in children and adolescents with ichthyosiform
      erythroderma in type IV and V skin.
AB  - BACKGROUND: Ichthyosiform erythroderma due to keratinizing disorders may suppress
      cutaneous vitamin D synthesis, leading to vitamin D deficiency and rickets.
      OBJECTIVES: To determine the prevalence of vitamin D deficiency and rickets in
      children and adolescents with congenital ichthyosis and other keratinizing
      disorders with erythroderma and scaling. PATIENTS AND METHODS: In this cross
      sectional study, 45 children and adolescents with ichthyosiform erythroderma due
      to keratinizing disorders, and 66 controls (group 1: age and sex matched, with
      skin diseases other than keratinizing disorders; group 2: age and sex matched,
      healthy volunteers) were included. Evidence of rickets was determined clinically
      (physical examination and radiographs) and biochemically {serum calcium,
      phosphorus, alkaline phosphatase, 25-hydroxy vitamin D [25(OH)D] and parathyroid
      hormone (PTH)}. RESULTS: All patients in the disease group had clinical,
      radiological or biochemical evidence of rickets [25(OH)D<20ngmL(-1) ], and
      analysis was done for all subjects with the available biochemical reports. The
      mean serum 25(OH)D levels of the disease group was 8.38+/-5.23ngmL(-1) and was
      significantly lower than in control group 1 (11.1+/-5.8ngmL(-1) ) (P<0.01) and
      control group 2 (13.5+/-6.9ngmL(-1) ) (P<0.001). The prevalence of vitamin D
      deficiency [25(OH)D<20ngmL(-1) ] was significantly higher in the disease group
      (n=38 of 39, 97.4%) than in control group 2 (n=12, 70.6%) (P<0.01), and total
      controls (n=56, 84.8%) (P=0.04). The frequency of hyperparathyroidism
      (PTH>65pgmL(-1) ) was also significantly higher in the disease group than in
      controls (P<0.01). CONCLUSIONS: Children and adolescents with various forms of
      ichthyosiform erythroderma, especially those with pigmented skin (types IV-VI),
      are at increased risk of developing vitamin D deficiency and clinical rickets.

PMID- 21967078
TI  - X-ray photoelectron spectroscopy depth profiling of La2O3/Si thin films deposited
      by reactive magnetron sputtering.
AB  - The La(2)O(3)/Si thin films have been deposited by reactive DC magnetron
      sputtering. Amorphous state of La(2)O(3) layer has been shown by RHEED
      observation. Top surface chemistry of the a-La(2)O(3) has been evaluated with
      layer-by-layer depth profiling by ion bombardment and XPS measurements. It was
      found by core level spectroscopy that the top surface of the a-La(2)O(3) film
      consists of hydrocarbon admixture, lanthanum carbonate, and hydroxides that
      formed as a result of contact with air atmosphere. Thickness of this top surface
      modified layer is below 1 nm for a contact time of ~1.5 h with air at normal
      conditions.

PMID- 21967077
TI  - A genetic predisposition score for muscular endophenotypes predicts the increase
      in aerobic power after training: the CAREGENE study.
AB  - BACKGROUND: It is widely accepted that genetic variability might explain a large
      part of the observed heterogeneity in aerobic capacity and its response to
      training. Significant associations between polymorphisms of different genes with
      muscular strength, anaerobic phenotypes and body composition have been reported.
      Muscular endophenotypes are positively correlated with aerobic capacity,
      therefore, we tested the association of polymorphisms in twelve muscular related
      genes on aerobic capacity and its response to endurance training. METHODS: 935
      Coronary artery disease patients (CAD) who performed an incremental exercise test
      until exhaustion at baseline and after three months of training were included.
      Polymorphisms of the genes were detected using the invader assay. Genotype
      phenotype association analyses were performed using ANCOVA. Different models for
      a genetic predisposition score (GPS) were constructed based on literature and own
      data and were related to baseline and response VO(2) scores. RESULTS: Carriers of
      the minor allele in the R23K polymorphism of the glucocorticoid receptor gene
      (GR) and the ciliary neurotrophic factor gene (CNTF) had a significantly higher
      increase in peakVO(2) after training (p < 0.05). Carriers of the minor allele
      (C34T) in the adenosine monophosphate deaminase (AMPD1) gene had a significantly
      lower relative increase (p < 0.05) in peakVO(2). GPS of data driven models were
      significantly associated with the increase in peakVO(2) after training.
      CONCLUSIONS: In CAD patients, suggestive associations were found in the GR, CNTF
      and the AMPD1 gene with an improved change in aerobic capacity after three months
      of training. Additionally data driven models with a genetic predisposition score
      (GPS) showed a significant predictive value for the increase in peakVO(2).

PMID- 21967079
TI  - Seasonal and weekly patterns of occurrence of acute cardiovascular diseases: does
      a gender difference exist?
AB  - BACKGROUND: Cardiovascular (CV) disease is the leading cause of death in women.
      It is known that acute CV events exhibit temporal patterns of onset, that is,
      seasonal and weekly. We aimed to verify whether such patterns show differences by
      gender. METHODS: We analyzed cumulative data from our previous studies dealing
      with hospital admissions for CV events, such as acute myocardial infarction
      (AMI), stroke, transient ischemic attack (TIA), aortic diseases (AD), and
      pulmonary embolism (PE), in the region Emilia-Romagna (RER) of Italy (ICDM9-CM
      codes, years 1998?2006). Total population and subgroups by gender (percentage of
      monthly and daily events) were tested for uniformity with the chi-square test,
      and a chronobiologic method was applied to monthly percentage of data for
      seasonal rhythmic analysis. RESULTS: Season: We considered 130,693 patients
      (45.1% women): 64,191 AMI, 43,642 TIA, 4,615 AD, 19,425 PE. The monthly and
      seasonal distribution showed respective peaks in January and in winter, with no
      differences by gender. Day-of-week: We considered 168,921 patients (45.6% women):
      64,191 AMI, 56,453 stroke, 43,642 TIA, 4,615 AD. The weekly distribution showed a
      peak on Monday, with no differences by gender. A multivariate regression logistic
      analysis, including in the model either major CV risk factors (hypertension,
      dyslipidemia, diabetes mellitus) and subgroups by age, did not find any
      difference in the temporal distribution of events in women and men. CONCLUSIONS:
      The seasonal and day-of-week distribution of occurrence of CV events seems to be
      independent of gender.

PMID- 21967080
TI  - A large coronary-pulmonary artery fistula in a cyanotic patient leading to severe
      biventricular dysfunction and heart failure.
AB  - In cases of pulmonary atresia (PA) with ventricular septal defect (VSD), the
      commonest source of pulmonary blood flow is via major aortoplumonary collaterals.
      Collaterals may also arise from the coronary arteries and the reported prevalence
      of such coronary-pulmonary artery fistulas (CPAF) in PA with VSD is 10%. However
      gross congestive heart failure (CHF) and ventricular dysfunction is extremely
      rare in such cases. We report a 17-year-old male with PA with VSD and a large
      CPAF from the anterior right aortic sinus connecting to the left pulmonary
      artery, who presented with severe CHF. The left anterior descending and the right
      coronary artery both arose from the proximal part of the CPAF, possibly leading
      to extensive coronary steal and biventricular dysfunction.

PMID- 21967081
TI  - Electrical breakdown of nanowires.
AB  - Instantaneous electrical breakdown measurements of GaN and Ag nanowires are
      performed by an in situ transmission electron microscopy method. Our results
      directly reveal the mechanism that typical thermally heated semiconductor
      nanowires break at the midpoint, while metallic nanowires breakdown near the two
      ends due to the stress induced by electromigration. The different breakdown
      mechanisms for the nanowires are caused by the different thermal and electrical
      properties of the materials.

PMID- 21967085
TI  - The influence of psycholinguistic variables on articulatory errors in naming in
      progressive motor speech degeneration.
AB  - We describe an analysis of speech errors on a confrontation naming task in a man
      with progressive speech degeneration of 10-year duration from Pick's disease.
      C.S. had a progressive non-fluent aphasia together with a motor speech impairment
      and early assessment indicated some naming impairments. There was also an absence
      of significant phonological or semantic impairment. In order to examine naming
      difficulties and the factors that influence his speech production errors, we
      selected 210 words varying in frequency, age of acquisition (AoA), imageability,
      phonemic length and syllable length and conducted a logistic regression analysis
      on a range of speech production error types (phone omissions, additions,
      substitutions, response delays, overall errors). No significant naming errors due
      to lexical access were found. The only significant predictor of speech
      articulation errors was phonemic length, with none of the other lexical variables
      influencing speech production error. The only error type predicted was phone
      omissions. Results suggest that C.S.'s speech and naming errors indicate
      compromised speech programming/planning rather than lexical selection and we
      conclude that this pattern of findings is indicative of problems with motor
      speech production.

PMID- 21967086
TI  - Endocervicoscopy: an important diagnostic tool in patients with cervical
      intraepithelial neoplasia undergoing LLETZ.

PMID- 21967087
TI  - Empathy, values, morality and Asperger's syndrome.
AB  - The aims of this study were, first, to re-address the issue of empathy among
      people with autism conditions; second, to explore the relationships between
      empathy and values among autistic populations and controls; and third, to explore
      the capacity for moral agency among those affected by autism. We compared
      responses of an Asperger group (N = 41) and a control group (N = 139) to measures
      of self-reported empathy (Davis's IRI) and value priorities (Schwartz's PVQ).
      Control group results were largely in line with previous studies, such that
      empathy subscales of perspective taking and empathic concern showed their
      strongest positive and negative relations to the Schwartz self-transcendence/self
      enhancement dimensions. Results for the Asperger group showed that although on
      the one hand there were self-reported difficulties in perspective taking and the
      cognitive recognition of affect, and that on the other hand there were less
      connections between the empathy and value measures, there was nevertheless a
      comparable prioritization of moral values. Conclusions suggest that different
      people may acquire moral values through different mechanisms.

PMID- 21967088
TI  - Methyl groups of trimethylamine N-oxide orient away from hydrophobic interfaces.
AB  - The molecular orientation of trimethylamine N-oxide (TMAO), a powerful protein
      stabilizer, was explored at aqueous/hydrophobic interfaces using vibrational sum
      frequency spectroscopy (VSFS). The systems studied included the
      octadecyltrichlorosilane (OTS)/water interface, which represents an aqueous
      solution in direct contact with a hydrophobic medium. Surprisingly, the
      measurements revealed that the methyl groups of TMAO pointed into the aqueous
      phase and away from the OTS. This orientation may arise from the more hydrophilic
      nature of methyl groups attached to a strongly electron-withdrawing atom such as
      a quaternary nitrogen. Additional studies were performed at the air/water
      interface. This interface showed a high degree of TMAO alignment, but the
      dangling OH from water was present even at 5 M TAMO. Moreover, the addition of
      this osmolyte modestly increased the surface tension of the interface. This meant
      that this species was somewhat depleted at the interface compared to the bulk
      solution. These findings may have implications for the stabilizing effect of TMAO
      on proteins. Specifically, the strong hydration required for the methyl groups as
      well as the oxide moiety should be responsible for the osmolyte's depletion from
      hydrophobic/aqueous interfaces. Such depletion effects should help stabilize
      proteins in their folded and native conformations on entropic grounds, although
      orientational effects may play an additional role.

PMID- 21967089
TI  - Triterpenoids with rare carbon skeletons from Salvia hydrangea: antiprotozoal
      activity and absolute configurations.
AB  - Salvadione C (1) and perovskone B (2), two new triterpenoids with rare carbon
      skeletons, were isolated from an antiplasmodial n-hexane extract of Salvia
      hydrangea. The absolute configuration was determined by comparison of
      experimental and calculated electronic circular dichroism (ECD) spectra. In vitro
      activity against Plasmodium falciparum K1 strain, Trypanosoma brucei rhodesiense
      STIB 900 strain, and cytotoxicity in rat myoblast (L6) cells were determined.
      Compounds 1 and 2 showed in vitro antiplasmodial activity, with IC50 values of
      1.43 and 0.18 MUM and selectivity indices (SI) of 86.2 and 69.6, respectively.
      IC50 values against T. brucei rhodesiense were found to be 4.33 and 15.92 MUM,
      respectively.

PMID- 21967090
TI  - Emergence of MRSA of unknown origin in the Netherlands.
AB  - The Netherlands is known for its low methicillin-resistant Staphylococcus aureus
      (MRSA) prevalence. Yet MRSA with no link to established Dutch risk factors for
      acquisition, MRSA of unknown origin (MUO), has now emerged and hampers early
      detection and control by active screening upon hospital admittance. We assessed
      the magnitude of the problem and determined the differences between MUO and MRSA
      of known origin (MKO) for CC398 and non-CC398. National MRSA Surveillance data
      (2008-2009) were analysed for epidemiological determinants and genotypic
      characteristics (Panton-Valentine leukocidin, spa). A quarter (24%) of the 5545
      MRSA isolates registered were MUO, i.e. not from defined risk groups. There are
      two genotypic MUO groups: CC398 MUO (352; 26%) and non-CC398 MUO (998; 74%).
      CC398 MUO needs further investigation because it could suggest spread, not by
      direct contact with livestock (pigs, veal calves), but through the community. Non
      CC398 MUO is less likely to be from a nursing home than non-CC398 MKO (relative
      risk 0.55; 95% CI 0.42-0.72) and Panton-Valentine leukocidin positivity was more
      frequent in non-CC398 MUO than MKO (relative risk 1.19; 95% CI 1.11-1.29). Exact
      transmission routes and risk factors for non-CC398 as CC398 MUO remain undefined.

PMID- 21967091
TI  - Testing bidirectional effects between cannabis use and depressive symptoms:
      moderation by the serotonin transporter gene.
AB  - Evidence for the assumption that cannabis use is associated with depression and
      depressive symptoms is inconsistent and mostly weak. It is likely that the mixed
      results are due to the fact that prior studies ignored the moderating effects of
      an individual's genetic vulnerability. The present study takes a first step in
      scrutinizing the relationship between cannabis use and depressive symptoms by
      taking a developmental molecular-genetic perspective. Specifically, we
      concentrated on changes in cannabis use and depressive symptoms over time in a
      simultaneous manner and differences herein for individuals with and without the
      short allele of the 5-hydroxytryptamine (serotonin) transporter gene-linked
      polymorphic region (5-HTTLPR) genotype. Data were from 310 adolescents over a
      period of 4 years. We used a parallel-process growth model, which allows co
      development of cannabis use and depressive symptoms throughout adolescence, and
      the possible role of the 5-HTTLPR genotype in this process. We used data from the
      younger siblings of these adolescents in an attempt to replicate potential
      findings. The parallel-process growth model shows that cannabis use increases the
      risk for an increase in depressive symptoms over time but only in the presence of
      the short allele of the 5-HTTLPR genotype. This effect remained significant after
      controlling for covariates. We did not find conclusive support for the idea that
      depressive symptoms affect cannabis use. These findings were replicated in the
      sample of the younger siblings. The findings of the present study show first
      evidence that the links between cannabis use and depressive symptoms are
      conditional on the individual's genetic makeup.

PMID- 21967092
TI  - Association of body mass with price of bushmeat in Nigeria and Cameroon.
AB  - Spatially extensive patterns of bushmeat extraction (and the processes underlying
      these patterns) have not been explored. We used data from a large sample (n= 87)
      of bushmeat trading points in urban and rural localities in Nigeria and Cameroon
      to explore extraction patterns at a regional level. In 7,594 sample days, we
      observed 61,267 transactions involving whole carcasses. Rural and urban trading
      points differed in species for sale and in meat condition (fresh or smoked).
      Carcass price was principally associated with body mass, with little evidence
      that taxonomic group (primate, rodent, ungulate, or mammalian carnivore) affected
      price. Moreover, meat condition was not consistently associated with price.
      However, some individual species were more expensive throughout the region than
      would be expected for their size. Prices were weakly positively correlated with
      human settlement size and were highest in urban areas. Supply did not increase
      proportionally as human settlement size increased, such that per capita supply
      was significantly lower in urban centers than in rural areas. Policy options,
      including banning hunting of more vulnerable species (those that have low
      reproductive rates), may help to conserve some species consumed as bushmeat
      because carcass prices indicate that faster breeding, and therefore the more
      sustainable species, may be substituted and readily accepted by consumers.

PMID- 21967093
TI  - Assessing the polycyclic aromatic hydrocarbon anisotropic potential with
      application to the exfoliation energy of graphite.
AB  - In this work we assess a recently published anisotropic potential for polycyclic
      aromatic hydrocarbon (PAH) molecules (J. Chem. Theory Comput. 2010, 6, 683-695).
      Comparison to recent high-level symmetry-adapted perturbation theory based on
      density functional theory (SAPT(DFT)) results for coronene (C(24)H(12))
      demonstrate the transferability of the potential while highlighting some
      limitations with simple point charge descriptions of the electrostatic
      interaction. The potential is also shown to reproduce second virial coefficients
      of benzene (C(6)H(6)) with high accuracy, and this is enhanced by using a
      distributed multipole model for the electrostatic interaction. The graphene dimer
      interaction energy and the exfoliation energy of graphite have been estimated by
      extrapolation of PAH interaction energies. The contribution of nonlocal
      fluctuations in the pi electron density in graphite have also been estimated
      which increases the exfoliation energy by 3.0 meV atom(-1) to 47.6 meV atom(-1),
      which compares well to recent theoretical and experimental results.

PMID- 21967094
TI  - Prediction of hand strength by hand injury severity scoring system in hand
      injured patients.
AB  - PURPOSE: Hand strength is a key component in human hand function, especially to
      those with strength-required jobs. To evaluate post-injury hand strength, this
      study was conducted to assess the predictability of hand injury severity scoring
      (HISS) system to hand strength after a period of recovery. METHODS: In this
      retrospective study, 80 traumatic hand-injured subjects were recruited. Hand
      strength tests measured by dynamometers were performed by subjects in ways of
      palmar pinch, lateral pinch and cylindrical grip. The logistic regression models
      were used to evaluate the risk of poor hand strength among the severities
      represented by HISS scores. RESULTS: A positive correlation exists between the
      differences of the strength of two hands, and the severity shown by HISS system
      in the poorer half of subjects. The risk to be in poorer half of palmar pinch
      subtest is significant in moderate subgroup of HISS severity. The risk to be in
      poorer half of cylindrical grip subtest is significant in major subgroup of HISS
      severity. The risk to be in poorer half of palmar pinch and cylindrical grip
      subtests is significant in skeletal component of HISS system. CONCLUSIONS: HISS
      is a descriptive severity scoring system to hand injury and also a useful
      instrument to predict functional outcome. This study revealed the HISS system may
      predict post-injury hand strength after recovery.

PMID- 21967095
TI  - Size dependence of chiroptical activity in colloidal quantum dots.
AB  - The synthesis of chiral penicillamine-capped CdS and CdSe quantum dots (QDs) was
      adjusted to control the size of the nanoparticles. This, together with size
      separation, allowed for simultaneous tuning of absorption, circular dichroism
      (CD), and fluorescence on a wide wavelength range. Band edge transitions were
      accompanied by circular dichroism peaks which red-shifted together with the
      increase in particle size. The clear correlation between absorption and CD bands
      as well as between absorption bands and size in semiconductor QDs was used to
      derive an experimental scaling law for optical activity. The decrease in the
      intensity of circular dichroism-to-absorption ratio (dissymmetry) with the
      increase in particle size was stronger than linear, probably exponential. In
      addition, strong material type dependence was observed. The CD line shape
      appeared to be sensitive to the nature of the transition and may thus serve as a
      tool for sorting out the electronic states of the QDs. Fluorescence-detected
      circular dichroism (FDCD) was introduced as a new probe of optically active
      fluorescent nanoparticles. The analysis of the size and material dependence of
      the chiroptical induction effect leads to the conclusion that it is primarily an
      electronic interaction effect between the adsorbed chiral molecules and the
      electron-hole states.

PMID- 21967096
TI  - Phase-selective synthesis of nickel phosphide in high-boiling solvent for all
      solid-state lithium secondary batteries.
AB  - Nickel phosphide particles were synthesized by thermal decomposition of a nickel
      precursor in a mixed solution of trioctylphosphine and trioctylphosphine oxide.
      The crystal phase and morphology of samples prepared by changing the solvents,
      the amount of trioctylphosphine as a phosphorus source, the reaction temperature,
      and the nickel precursor were characterized using X-ray diffraction and
      transmission electron microscopy. Spherical Ni(5)P(4) particles with diameters of
      500 nm were obtained using nickel acetylacetonate as a nickel precursor at 360 
      degrees C for 1 h in trioctylphosphine oxide. NiP(2) particles with diameters of
      200-500 nm were obtained using nickel acetate tetrahydrate at 360  degrees C for
      5 h in trioctylphosphine oxide. All-solid-state cells were fabricated using
      NiP(2) particles as an active material and 80Li(2)S.20P(2)S(5) (mol %) glass
      ceramic as a solid electrolyte. The Li-In/80Li(2)S.20P(2)S(5)/NiP(2) cell
      exhibited an initial discharge capacity of 1100 mAh g(-1) at a current density of
      0.13 mA cm(-2) and retained a discharge capacity of 750 mAh g(-1) after 10
      cycles.

PMID- 21967097
TI  - Infection control in veterinary practice; the time is now.

PMID- 21967098
TI  - The effect of boric acid on bacterial culture of canine and feline urine.
AB  - OBJECTIVE: To identify the optimal method of submission of canine and feline
      urine for bacterial culture. METHODS: Cystocentesis samples from 250 animals (200
      dogs, 50 cats) suspected of having urinary tract infections were collected. The
      reference aliquot, without preservative, was processed on site within 2 hours.
      Two further aliquots (one without preservative, one with boric acid) were stored
      at room temperature for up to 7 hours and then posted by guaranteed next day
      delivery to a commercial laboratory for analysis. RESULTS: Forty-seven of the
      samples were positive on culture in the reference test. There was no significant
      difference between reference test results and those of samples posted without
      preservative (P=0.39), but samples posted in boric acid were significantly less
      likely to give a positive result (P=0.01). Samples posted without preservative
      had a sensitivity of 82% and a specificity of 98%; for boric acid, sensitivity
      was 73% and specificity 99%. CLINICAL SIGNIFICANCE: Postal urine samples should
      be submitted to the laboratory in a plain sterile tube.

PMID- 21967099
TI  - Contrast-enhanced ultrasonography in the differentiation of retinal detachment
      and vitreous membrane in dogs and cats.
AB  - OBJECTIVES: To evaluate contrast-enhanced ultrasonography (CEU) and colour
      Doppler imaging (CDI) for detection of persistent vascularisation in retinal
      detachment. METHODS: In 22 eyes, retinal detachment (n=13) and vitreous membranes
      (n=9) were confirmed by ophthalmological examination, during cataract surgery, by
      histopathology or after vitreoretinal surgery. Tentative diagnosis of retinal
      detachment or vitreous membrane was made using grey-scale B-mode ultrasonography.
      Assessment of retinal detachment was based on the presence or absence of
      vascularisation in the membranous structure using CDI and CEU. RESULTS:
      Sensitivity, specificity, positive-predictive value and negative-predictive value
      of grey-scale ultrasonography in differentiating retinal detachment from vitreous
      membrane were 92.3%, 66.6%, 80% and 85.7%. In 91% of eyes, colour Doppler
      assessment was unsuccessful due to the movement of the eye. Persistent
      vascularisation was demonstrated in all cases of retinal detachments with CEU.
      CEU was 100% accurate for detection and differentiation between retinal
      detachment and vitreous membrane. CLINICAL SIGNIFICANCE: CEU is a useful clinical
      tool for the diagnosis of retinal detachment and vitreous membrane in dogs and
      cats.

PMID- 21967100
TI  - Canine hip dyslasia: the significance of the Norberg angle for healthy breeding.
AB  - OBJECTIVES: To assess the reproducibility of the Federation Cynologique
      Internationale (FCI) classification over time, and between assessors and to
      evaluate the benefit of computer-assisted measurement of the Norberg angle and of
      its percentile ranking by breed for the diagnosis of canine hip dysplasia, and
      for the selection of couples for breeding. METHODS: During the time period of
      2006 to 2010, 5094 hip radiographs were evaluated according to the FCI rules, and
      4400 have been submitted for statistical analysis. A system of computer-assisted
      image analysis (Digimizer((r)) , MedCalc Software Ltd, Mariakerke, Belgium) was
      used to measure the Norberg angle. The Norberg angle value of individual dogs was
      expressed as percentile rank by breed. RESULTS: The agreement between individual
      assessors was highly significant (P<0.001), but there were important variations
      over time of the ratio of classes A or B. The Norberg angle and the percentile
      rank accurately discriminated between dogs with or without canine hip dysplasia,
      with positive and negative likelihood ratios of 6.31 and 0.21, respectively, for
      the Norberg angle at criterion value of 102.2 degrees , and 4.21 and 0.18 for the
      percentile rank at criterion value of the 25th percentile. CLINICAL SIGNIFICANCE:
      The percentile rank of the Norberg angle may be a valuable tool for breeding
      selection.

PMID- 21967101
TI  - Traumatic urothorax in a dog: a case report.
AB  - Pleural effusion caused by post-traumatic extravasation of urine from the
      abdominal cavity to the pleural cavity (urothorax) is an uncommon complication
      following traumatic injury. To the authors' knowledge, this is the first report
      of a case of traumatic urothorax in a dog presented with pleural and abdominal
      urine effusion. Combined urothorax and uroabdomen should be included in the
      differential-diagnosis list for dogs with recent trauma and a bicavitary
      effusion. The diagnosis can be confirmed by elevated creatinine concentrations in
      both effusates, compared to its serum concentration.

PMID- 21967102
TI  - Neuromyotonia in a dachshund with clinical and electrophysiological signs of
      spinocerebellar ataxia.
AB  - A 10-month-old dachshund was presented with a recent history of episodic muscle
      rippling and generalised stiffness. An uncoordinated gait was present since eight
      weeks of age. On presentation the dog showed cerebellar-like ataxia and poor
      menace responses. Myokymic contractions were visible in the appendicular and
      truncal muscles and neuromyotonic discharges were detected by electromyography.
      Central components of the brain auditory evoked potentials were absent and the
      onset latencies of the tibial sensory-evoked potentials recorded at the lumbar
      intervertebral level were delayed. Response to slow-release phenytoin was
      temporary. The clinical picture together with the electrophysiological findings
      in this dachshund are identical to the findings in Jack Russell terriers with
      hereditary ataxia and neuromyotonia. This is the first description of
      neuromyotonia associated with clinical and electrophysiological signs of
      spinocerebellar ataxia in a breed other than the Jack Russell terrier. This case
      also strengthens the theory that spinocerebellar ataxia and neuromyotonia are
      related. An ion channel dysfunction is presumed to link both disorders.

PMID- 21967106
TI  - Bias in canine lifespan estimates through right censored data.

PMID- 21967108
TI  - Proteomic identification of protease cleavage sites characterizes prime and non
      prime specificity of cysteine cathepsins B, L, and S.
AB  - Cysteine cathepsins mediate proteome homeostasis and have pivotal functions in
      diseases such as cancer. To better understand substrate recognition by cathepsins
      B, L, and S, we applied proteomic identification of protease cleavage sites
      (PICS) for simultaneous profiling of prime and non-prime specificity. PICS
      profiling of cathepsin B endopeptidase specificity highlights strong selectivity
      for glycine in P3' due to an occluding loop blocking access to the primed
      subsites. In P1', cathepsin B has a partial preference for phenylalanine, which
      is not found for cathepsins L and S. Occurrence of P1' phenylalanine often
      coincides with aromatic residues in P2. For cathepsin L, PICS identifies 845
      cleavage sites, representing the most comprehensive PICS profile to date.
      Cathepsin L specificity is dominated by the canonical preference for aromatic
      residues in P2 with limited contribution of prime-site selectivity determinants.
      Profiling of cathepsins B and L with a shorter incubation time (4 h instead of 16
      h) did not reveal time-dependency of individual specificity determinants.
      Cathepsin S specificity was profiled at pH 6.0 and 7.5. The PICS profiles at both
      pH values display a high degree of similarity. Cathepsin S specificity is
      primarily guided by aliphatic residues in P2 with limited importance of prime
      site residues.

PMID- 21967109
TI  - CD147-targeting siRNA inhibits cell-matrix adhesion of human malignant melanoma
      cells by phosphorylating focal adhesion kinase.
AB  - CD147/basigin, highly expressed on the surface of malignant tumor cells including
      malignant melanoma (MM) cells, plays a critical role in the invasiveness and
      metastasis of MM. Metastasis is an orchestrated process comprised of multiple
      steps including adhesion and invasion. Integrin, a major adhesion molecule, co
      localizes with CD147/basigin on the cell surface. Using the human MM cell line
      A375 that highly expresses CD147/basigin, we investigated whether CD147/basigin
      is involved in adhesion in association with integrin. CD147/basigin was knocked
      down using siRNA targeting CD147 to elucidate the role of CD147/basigin. Cell
      adhesion was evaluated by adhesion assay on matrix-coated plates. The
      localization of integrin was inspected under a confocal microscope and the
      expression and phosphorylation of focal adhesion kinase (FAK), a downstream
      kinase of integrin, were examined by western blot analysis. Silencing of
      CD147/basigin in A375 cells by siRNA induced the phosphorylation of FAK at Y397.
      Integrin identified on the surface of parental cells was distributed in a
      speckled fashion in the cytoplasm of CD147 knockdown cells, resulting in
      morphological changes from a round to a polygonal shape with pseudopodial
      protrusions. Silencing of CD147/basigin in A375 cells clearly weakened their
      adhesiveness to collagen I and IV. Our results suggest that CD147/basigin
      regulates the adhesion of MM cells to extracellular matrices and of integrin
      beta1 signaling via the phosphorylation of FAK.

PMID- 21967110
TI  - Infrared heat treatment reduces food intake and modifies expressions of TRPV3
      POMC in the dorsal medulla of obesity prone rats.
AB  - PURPOSE: Infrared heat, a transient receptor potential vanilloid type-3 (TRPV3)
      sensitive stimulus, may have potential physiological effects beneficial to
      treating metabolic syndrome. MATERIALS AND METHODS: Obesity prone (OP) and
      obesity resistant (OR) rats were fed for seven days on a high-fat diet. Heat
      treated OP rats were exposed twice daily to infrared light for 20 min each,
      separated by 80 min of rest. Food intake, blood pressure, blood glucose, and body
      weight measurements were taken daily and compared between treated OP rats,
      untreated OP rats, and OR controls. The animals were perfused with 4%
      paraformaldehyde, and immunohistochemistry was performed on the coronal brainstem
      sections with polyclonal antibodies against TRPV3 and pro-opiomelanocortin
      (POMC). The positive-staining cells in the medulla nuclei were quantified using a
      microscope with reticule grid. RESULTS: Food intake, body weight, and mean
      arterial blood pressure (MAP) were higher in OP rats, a diet-induced metabolic
      syndrome model, accompanied by a reduced expression of POMC, an anorectic agent,
      in the hypoglossal nucleus (HN) and medial nucleus tractus solitarius (mNTS).
      Food intake in heat-treated OP rats was significantly decreased. POMC positive
      neuron count was increased in the HN and mNTS of OP rats following treatment.
      TRPV3 positive staining neurons were increased in the HN and mNTS of OP control
      rats and decreased following the heat treatments. CONCLUSION: Lowered POMC and
      heightened TRPV3 expressions in the HN and mNTS are involved in development of
      hyperphagia and obesity in OP rats. Exposure to infrared heat modifies TRPV3 and
      POMC expression in the brainstem, reducing food intake.

PMID- 21967111
TI  - What's past is prologue: developmental pathways and chronic allograft
      dysfunction.

PMID- 21967113
TI  - Evidence-Based Dermatology: Everyone's Business.

PMID- 21967114
TI  - Second-generation H1-antihistamines in chronic urticaria: an evidence-based
      review.
AB  - The effects of urticaria are predominantly mediated by histamine release;
      therefore, H1-antihistamines are the mainstay of treatment. Second-generation H1
      antihistamines, compared with their first-generation counterparts, have
      demonstrated improved peripheral H1-receptor selectivity and decreased
      lipophilicity (which minimizes CNS adverse effects), and antiallergic properties
      in addition to being histamine inverse agonists. Evidence of clinical efficacy
      and tolerability of second-generation H1-antihistamines available in the US for
      the treatment of chronic urticaria (CU) was analyzed using the GRADE system to
      develop the strength of recommendations for particular therapies. The evidence
      for the safety and efficacy of the majority of second-generation H1
      antihistamines available in the US is of high quality and leads to a strong
      recommendation for their use in CU. There is a limited amount of data of variable
      quality comparing the efficacy between various second-generation H1
      antihistamines in CU leading to weak recommendations for using cetirizine over
      fexofenadine and levocetirizine over desloratadine. Limited data of variable
      quality exist for the efficacy of higher doses of second-generation H1
      antihistamines in CU patients not responsive to standard doses. These limited
      data lead to a strong recommendation that higher than recommended doses of
      fexofenadine do not offer greater efficacy in control of CU and a weak
      recommendation that higher doses of levocetirizine and desloratadine are more
      effective in CU unresponsive to standard doses. More studies of higher quality
      are required to make any firm recommendations regarding second-generation H1
      antihistamines in the treatment of physical urticarias. All second-generation H1
      antihistamines appear to be very well tolerated in CU patients, with rare reports
      of adverse effects. Due to the relatively large gaps in the quantity and quality
      of evidence, particularly for choice of H1-antihistamines, use of higher doses,
      and use in physical urticarias, greater emphasis in management decisions should
      be based on the risk/benefit ratio and the patient's personal values and
      preferences (including cost) in clinical decision making.

PMID- 21967115
TI  - Topical diphencyprone immunotherapy for a large primary melanoma on an elderly
      leg.

PMID- 21967116
TI  - Adapalene 0.1%/benzoyl peroxide 2.5% gel: a review of its use in the treatment of
      acne vulgaris in patients aged >= 12 years.
AB  - Adapalene 0.1%/benzoyl peroxide 2.5% gel (EpiduoTM, TactuoTM) is the only fixed
      dose combination product available that combines a topical retinoid with benzoyl
      peroxide; it targets three of the four main pathophysiologic factors in acne.
      This article reviews the therapeutic efficacy and tolerability of topical
      adapalene 0.1%/benzoyl peroxide 2.5% gel in the treatment of patients aged >= 12
      years with acne vulgaris, as well as summarizing its pharmacologic properties. In
      three 12-week trials in patients aged >= 12 years with moderate acne, success
      rates were significantly higher with adapalene 0.1%/benzoyl peroxide 2.5% gel
      than with adapalene 0.1% gel or benzoyl peroxide 2.5% gel alone, and combination
      therapy had an earlier onset of action. In addition, significantly greater
      reductions in total, inflammatory, and noninflammatory lesion counts were seen in
      patients receiving adapalene 0.1%/benzoyl peroxide 2.5% gel than in those
      receiving adapalene 0.1% gel or benzoyl peroxide 2.5% gel alone. Adapalene
      0.1%/benzoyl peroxide 2.5% gel did not significantly differ from clindamycin
      1%/benzoyl peroxide 5% gel in terms of the reduction in the inflammatory,
      noninflammatory, or total lesion counts in patients with mild to moderate acne,
      according to the results of a 12-week trial. Twelve-week studies showed that
      topical adapalene 0.1%/benzoyl peroxide 2.5% gel in combination with oral
      lymecycline was more effective than oral lymecycline alone in patients with
      moderate to severe acne, and topical adapalene 0.1%/benzoyl peroxide 2.5% gel in
      combination with oral doxycycline hyclate was more effective than oral
      doxycycline hyclate alone in patients with severe acne. In patients with severe
      acne who responded to 12 weeks' therapy with topical adapalene 0.1%/benzoyl
      peroxide 2.5% gel plus oral doxycycline hyclate or oral doxycycline hyclate
      alone, an additional 6 months' therapy with adapalene 0.1%/benzoyl peroxide 2.5%
      gel was more effective than vehicle gel at maintaining response, with further
      improvement seen in adapalene 0.1%/benzoyl peroxide 2.5% gel recipients. A
      noncomparative study also demonstrated the efficacy of 12 months' therapy with
      adapalene 0.1%/benzoyl peroxide 2.5% gel in patients with acne vulgaris. Topical
      adapalene 0.1%/benzoyl peroxide 2.5% gel was generally well tolerated in patients
      with acne. In 12-week trials, the most commonly occurring treatment-related
      adverse events included erythema, scaling, dryness, and stinging/burning; these
      dermatologic treatment-related adverse events were usually of mild to moderate
      severity, occurred early in the course of treatment, and resolved without
      residual effects. Topical adapalene 0.1%/benzoyl peroxide 2.5% gel was generally
      well tolerated in the longer term, with dry skin being the most commonly
      occurring treatment-related adverse event over 12 months of treatment. In
      conclusion, adapalene 0.1%/benzoyl peroxide 2.5% gel is a valuable agent for the
      first-line treatment of acne vulgaris.

PMID- 21967117
TI  - Spotlight on calcipotriene/betamethasone dipropionate in psoriasis vulgaris of
      the trunk, limbs, and scalp.
AB  - Calcipotriene (calcipotriol)/betamethasone dipropionate (calcipotriene 50 MUg/g
      and betamethasone 0.5 mg/g) is a fixed-dose combination of a vitamin D3 analog
      and a corticosteroid indicated for the once-daily, topical treatment of psoriasis
      vulgaris of the trunk, limbs, and scalp in adults. Both the ointment
      (Daivobet(r); Dovobet(r)) and gel (Xamiol(r); Daivobet(r) Gel; Dovobet(r) Gel)
      formulations of calcipotriene/betamethasone dipropionate can be used to treat
      psoriasis vulgaris of the trunk and/or limbs, although the gel formulation was
      specifically developed for the treatment of scalp psoriasis. This article reviews
      the efficacy and tolerability of calcipotriene/betamethasone dipropionate in
      patients with psoriasis vulgaris, as well as summarizing its pharmacologic
      properties. Calcipotriene/betamethasone dipropionate has low systemic absorption
      and displays local anti-inflammatory and immunoregulatory properties. It reduces
      the hyperproliferation of keratinocytes and helps normalize keratinocyte
      differentiation. In large, well designed clinical trials,
      calcipotriene/betamethasone dipropionate, either as the ointment or the gel
      formulation, applied once daily for 4-8 weeks, was more effective than placebo,
      calcipotriene, or tacalcitol, as well as betamethasone dipropionate in most
      instances, for the topical, symptomatic treatment of psoriasis vulgaris of the
      trunk/limbs. Likewise, calcipotriene/betamethasone dipropionate gel applied once
      daily for 8 weeks was more effective than placebo or either component alone in
      the topical, symptomatic treatment of psoriasis vulgaris of the scalp. Long-term,
      once-daily, when required therapy with calcipotriene/betamethasone dipropionate
      for 52 weeks was more effective than calcipotriene alone for the treatment of
      scalp psoriasis, and was at least as effective as switching to calcipotriene for
      48 weeks after 4 weeks of calcipotriene/betamethasone dipropionate or alternating
      between calcipotriene/betamethasone dipropionate and calcipotriene every 4 weeks
      for 52 weeks in the treatment of psoriasis vulgaris of the trunk/limbs.
      Calcipotriene/betamethasone dipropionate also improved health-related quality of
      life. Calcipotriene/betamethasone dipropionate was generally well tolerated, with
      most adverse drug reactions being lesional or perilesional effects of mild or
      moderate severity. Calcipotriene/betamethasone dipropionate was often associated
      with fewer lesional/perilesional adverse reactions than calcipotriene or
      tacalcitol and did not appear to be associated with a higher incidence of
      corticosteroid-related adverse events during long-term therapy. Pharmacoeconomic
      analyses predicted calcipotriene/betamethasone dipropionate to be more cost
      effective than other topical therapies. Thus, calcipotriene/betamethasone
      dipropionate is an important, effective, once-daily, topical therapy for the
      symptomatic treatment of psoriasis vulgaris of the trunk, limbs, and scalp.

PMID- 21967118
TI  - Analyzing longitudinal data with missing values.
AB  - Missing data methodology has improved dramatically in recent years, and popular
      computer programs now offer a variety of sophisticated options. Despite the
      widespread availability of theoretically justified methods, researchers in many
      disciplines still rely on subpar strategies that either eliminate incomplete
      cases or impute the missing scores with a single set of replacement values. This
      article provides readers with a nontechnical overview of some key issues from the
      missing data literature and demonstrates several of the techniques that
      methodologists currently recommend. This article begins by describing Rubin's
      missing data mechanisms. After a brief discussion of popular ad hoc approaches,
      the article provides a more detailed description of five analytic approaches that
      have received considerable attention in the missing data literature: maximum
      likelihood estimation, multiple imputation, the selection model, the shared
      parameter model, and the pattern mixture model. Finally, a series of data
      analysis examples illustrate the application of these methods.

PMID- 21967119
TI  - Severity of children's intellectual disabilities and Medicaid personal care
      services.
AB  - OBJECTIVES: This research investigated the relationship between a child's
      reported intellectual disability (ID) level and caregivers' reports of the
      child's health status to predict Medicaid Personal Care Services (PCS) hours
      authorized for that child. We also investigated how activity limitations in the
      home varied with the level of ID. DESIGN: The sample included 1,108 community
      residing children with a reported level of ID in the Texas Medicaid system and
      who were assessed for the PCS program. All data were collected with the Personal
      Care Assessment Form (PCAF), an instrument developed by the authors for
      evaluating children's PCS needs. Case managers completed the PCAF in the child's
      home with the child and primary caregivers present. Structural equation modeling
      (SEM) was used to test a model reflecting the role of ID and other
      characteristics of the child in determining the number of PCS hours authorized.
      Additional analyses revealed the degree to which variation among the case
      managers affected the number of hours authorized. RESULTS: ID level and other
      individual characteristics had a significant effect on reports of a child's
      activity limitations (R2 = .67), which in turn affected the hours of PCS
      authorized (R2 = .27). We found no significant direct relationship between ID
      level and PCS hours: ID level had an indirect relationship on PCS hours through
      activity limitations. When the variance in hours authorized was decomposed,
      individual characteristics accounted for 20% of the variance and case managers
      accounted for 14%. CONCLUSIONS: Assessments of caregiver and child strengths and
      limitations in the home are critical in the allocation of Medicaid home-based
      services, above and beyond the information conveyed by demographic and diagnostic
      data. Implications for home-based assessments of functional limitations and needs
      for family caregivers and their children with ID are discussed.

PMID- 21967120
TI  - Sequence comparison of prefrontal cortical brain transcriptome from a tame and an
      aggressive silver fox (Vulpes vulpes).
AB  - BACKGROUND: Two strains of the silver fox (Vulpes vulpes), with markedly
      different behavioral phenotypes, have been developed by long-term selection for
      behavior. Foxes from the tame strain exhibit friendly behavior towards humans,
      paralleling the sociability of canine puppies, whereas foxes from the aggressive
      strain are defensive and exhibit aggression to humans. To understand the genetic
      differences underlying these behavioral phenotypes fox-specific genomic resources
      are needed. RESULTS: cDNA from mRNA from pre-frontal cortex of a tame and an
      aggressive fox was sequenced using the Roche 454 FLX Titanium platform (> 2.5
      million reads & 0.9 Gbase of tame fox sequence; >3.3 million reads & 1.2 Gbase of
      aggressive fox sequence). Over 80% of the fox reads were assembled into contigs.
      Mapping fox reads against the fox transcriptome assembly and the dog genome
      identified over 30,000 high confidence fox-specific SNPs. Fox transcripts for
      approximately 14,000 genes were identified using SwissProt and the dog RefSeq
      databases. An at least 2-fold expression difference between the two samples (p <
      0.05) was observed for 335 genes, fewer than 3% of the total number of genes
      identified in the fox transcriptome. CONCLUSIONS: Transcriptome sequencing
      significantly expanded genomic resources available for the fox, a species without
      a sequenced genome. In a very cost efficient manner this yielded a large number
      of fox-specific SNP markers for genetic studies and provided significant insights
      into the gene expression profile of the fox pre-frontal cortex; expression
      differences between the two fox samples; and a catalogue of potentially important
      gene-specific sequence variants. This result demonstrates the utility of this
      approach for developing genomic resources in species with limited genomic
      information.

PMID- 21967127
TI  - Controllable growth of highly ordered ZnO nanorod arrays via inverted self
      assembled monolayer template.
AB  - This article presents a facile and effective approach to the controllable growth
      of highly ordered and vertically aligned ZnO nanorod arrays on the GaN substrate
      via a hydrothermal route by using the TiO(2) ring template deriving from the
      polystyrene microsphere self-assembled monolayer. The size of TiO(2) ring
      template can be flexibly tuned from 50 to 400 nm for the 500 nm polystyrene
      microspheres by varying the time of reactive ion etching and the concentration of
      TiO(2) sol. As a result, the diameter of the individual ZnO nanorods can be
      potentially tuned over a wide range. The combination of several characterization
      techniques has demonstrated that the ordered ZnO nanorods are highly uniform in
      diameter and height with perfect alignment and are epitaxially grown along [0001]
      direction. This work provides a novel and accessible route to prepare oriented
      and aligned ZnO nanorod arrays with high crystalline quality.

PMID- 21967121
TI  - Disturbed sleep, a novel risk factor for preterm birth?
AB  - OBJECTIVE: The etiology of preterm birth (PTB) is likely caused by multiple
      factors, which may include disturbed sleep. We evaluated whether sleep
      disturbance was associated with PTB and whether the association was affected by
      other psychosocial risk factors. METHODS: Pregnant women (n=217) for whom we had
      depression and sleep data at 20 or 30 weeks gestation and delivery information
      were evaluated. Logistic models were used to test the hypotheses that disturbed
      sleep was associated with PTB. RESULTS: Time in bed at 20 weeks was significantly
      associated with risk for preterm delivery (odds ratio [OR] 1.43, 95% confidence
      interval [CI] 1.08-1.88). However, after controlling for depression/selective
      serotonin reuptake inhibitors (SSRI) status, history of PTB, age, employment, and
      marital status, this relationship was no longer significant (OR 1.26, 95% CI .92
      1.71). No other relationships were significant. CONCLUSIONS: We report
      preliminary evidence suggesting that poor sleep may contribute to risk for PTB.
      Although it is speculative and additional work is needed to confirm or refute
      whether sleep is an independent or mediating risk factor for PTB, disturbed sleep
      does appear to play a role in adverse pregnancy outcomes.

PMID- 21967128
TI  - Electron beam irradiation stiffens zinc tin oxide nanowires.
AB  - We report a remarkable phenomenon that electron beam irradiation (EBI)
      significantly enhances the Young's modulus of zinc tin oxide (ZTO) nanowires
      (NWs), up to a 40% increase compared with the pristine NWs. In situ uniaxial
      buckling tests on individual NWs were conducted using a nanomanipulator inside a
      scanning electron microscope. We propose that EBI results in substantial atomic
      bond contraction in ZTO NWs, accounting for the observed mechanically stiffening.
      This argument is supported by our experimental results that EBI also reduces the
      electrical conductivity of ZTO NWs.

PMID- 21967129
TI  - Using EPG data to display articulatory separation for phoneme contrasts.
AB  - A recurring difficulty for researchers using electropalatography (EPG) is the
      wide variation in spatial patterns that occurs between speakers. High inter
      speaker variability, combined with small numbers of participants, makes it
      problematic (1) to identify differences in tongue-palate contact across groups of
      speakers and (2) to define 'normal' patterns during visual feedback therapy. This
      article shows how graphing EPG data in terms of articulatory separation of
      phoneme contrasts reduces these two problems to some extent. The graphs emphasise
      the importance of establishing the presence and extent of separation, as revealed
      in the EPG data, for phoneme contrasts produced by speakers. Separation graphs
      for contrasts /i/ - /u/, /s/ - /?/ and /t/ - /k/ are presented using EPG data
      from adults and children with typical speech and those with speech disorders.
      When used in conjunction with acoustic and auditory perceptual analyses, it is
      proposed that representing articulation data in terms of separation will prove
      useful for a range of clinical and research purposes.

PMID- 21967130
TI  - The value of live three-dimensional echocardiography in an adult patient with
      aortico-left ventricular tunnel.
AB  - Aortico-left ventricular tunnel (ALVT) is a rare cardiac abnormality. This
      article presents an adult case of ALVT with aortic ostium lying above the left
      noncommissure which was diagnosed with live three-dimensional echocardiography
      (3DE). Live 3DE has shown its value in providing more detailed information. 

PMID- 21967131
TI  - An international reference reagent for the detection of RHD and SRY DNA in
      plasma.
AB  - BACKGROUND AND OBJECTIVES: The determination of foetal RHD genotype using foetal
      DNA contained in the maternal circulation is increasingly used to manage
      pregnancies at risk of haemolytic disease of the foetus and newborn (HDFN) caused
      by maternal anti-D. The test is becoming increasingly reliable, and routine
      clinical services have been established in some centres. However, laboratories
      currently have no reference materials with which to determine the performance of
      their tests. This report describes the production and evaluation of a freeze
      dried preparation of human plasma, code 07/222, containing RHD and SRY sequences
      which can be used as a minimum sensitivity reagent. MATERIALS AND METHODS: RhD
      positive male plasma was diluted in an excess of RhD-negative female plasma, and
      1 ml aliquots were freeze-dried in glass ampoules. To characterise the material,
      19 laboratories took part in an international collaborative study. The
      participants evaluated dilutions of the material using their in-house routine
      assays and recorded the highest dilution where the genes could be detected.
      RESULTS: When diluted 1 in 2, most laboratories were able to detect the presence
      of RHD and SRY sequences in the material and the participants agreed that this
      was an appropriate level to set as the minimum sensitivity required. CONCLUSIONS:
      In October 2010, the WHO Expert Committee on Biological Standardization approved
      the material 07/222 as an International Reference Reagent for the detection of
      RHD and SRY DNA in plasma.

PMID- 21967132
TI  - Topical nitrogen mustard therapy in patients with Langerhans cell histiocytosis.
AB  - BACKGROUND: Langerhans cell histiocytosis (LCH) is characterized by abnormal
      proliferation and infiltration of Langerhans cells in different organs. The skin
      is frequently involved either as unisystem or multisystem disease. OBJECTIVES: To
      review the clinical response and side-effects of nitrogen mustard therapy in LCH
      in children and adults with unisystem or multisystem disease. PATIENTS AND
      METHODS: This retrospective study includes 10 children and four adults with LCH,
      treated with nitrogen mustard from 1975 to 2010. The median extent of skin
      involvement was 46% (range 5-100%). RESULTS: Overall, 13 patients had complete or
      partial response. Although eight patients achieved a complete response with a
      median time of 12.3months (range 36 days to 1.9 years), six of these patients
      ultimately relapsed. One patient, who had unisystem disease limited to the skin,
      initially showed progression of her cutaneous lesions with nitrogen mustard
      treatment. Although subsequently the cutaneous lesions completely regressed,
      concomitant systemic involvement was noted. Four other patients similarly
      experienced improvement of their skin lesions with treatment, but also exhibited
      progression of the LCH systemically. The patients were treated with other
      therapies prior and adjunctive to nitrogen mustard. However, five patients had
      progression to other organs, despite regression of skin lesions, which supports
      that the treatment effect in the skin is related to topical nitrogen mustard. Six
      patients developed contact dermatitis to nitrogen mustard. CONCLUSIONS: Topical
      nitrogen mustard can be an effective and safe therapy in both children and adults
      with cutaneous LCH, although relapses are common.

PMID- 21967133
TI  - A marked synergistic effect in antitumor activity of salan titanium(IV) complexes
      bearing two differently substituted aromatic rings.
AB  - Salan titanium(IV) complexes of differently substituted aromatic rings, where one
      ring is para-nitrated and another is ortho,para-halogenated, demonstrate
      exceptionally high anticancer activity, with IC(50) values of <1 MUM, exceeding
      that of cisplatin by ~30-fold. Whereas an additive effect in hydrolytic stability
      was detected for these highly stable complexes, an unexpected synergistic effect
      in anticancer activity makes these hybrid complexes substantially more active
      than both their symmetrical analogues alone and their equimolar mixture.

PMID- 21967134
TI  - Simultaneous HAART improves survival in children coinfected with HIV and TB.
AB  - OBJECTIVES: This study assesses the outcome of current treatment guidelines and
      the effect of highly active antiretroviral therapy (HAART) on survival of HIV/TB
      coinfected patients in a resource-limited setting. METHODS: Observational cohort
      study at the pediatric HIV Clinic, RML Hospital, Delhi. All HIV-infected patients
      who visited the clinic for the diagnosis of TB between 2002 and 2006 were
      observed until 31 March 2010. TB was diagnosed either at the time of enrolment or
      during follow-up visits. Clinical and epidemiological data were registered. We
      compared children who were given HAART with TB treatment at time of diagnosis
      [simultaneous therapy (ST)] and children who received delayed HAART. Survival was
      assessed by Kaplan-Meier method and Cox regression model. RESULTS: Among the 298
      children, 126 (42.2%) had TB, including 96 who received ST (76% of 126) and 30
      who did not. There were no differences between the two groups except for a lower
      CD4 count in patients undergoing ST. ST was associated with improved survival
      [hazard ratio (HR), 0.35; 95% CI, 0.20-0.74; P = 0.002] and so were year of TB
      diagnosis and other AIDS-defining conditions. Multivariate analysis revealed that
      ST was a powerful predictor of survival (HR, 0.30; 95% CI, 0.14-0.68; P = 0.003).
      After adjusting for other prognostic variables such as age, gender, CD4 count at
      time of TB diagnosis, by Cox multivariate analysis, ST remained robustly
      associated with improved survival (HR, 0.32; 95% CI, 0.17-0.71; P = 0.001).
      CONCLUSIONS: Starting HAART during tuberculosis therapy significantly improves
      survival and provides further impetus for the integration of TB and HIV services.

PMID- 21967135
TI  - Pension insecurities for public employees.

PMID- 21967136
TI  - Aging in poverty: making the case for comprehensive care management.
AB  - A model for holistic care management that would enhance outcomes for economically
      vulnerable older adults who receive an array of disjointed services administered
      through the older Americans Act (OAA) and local Area Agencies on Aging (AAA) is
      proposed. Fragmented service delivery is typically wasteful and ineffectual, but
      comprehensive care management that includes an autonomous care manager, a single
      interagency plan of care and ongoing monitoring that is client-centered may
      protect those aging in poverty from negative health outcomes.

PMID- 21967137
TI  - Awareness of LGBT aging issues among aging services network providers.
AB  - Very little research exists examining the interactions between community-based
      aging service providers and lesbian, gay, bisexual, and transgender (LGBT) older
      adults. It is unclear whether mainstream aging services acknowledge the needs of
      this community. We asked direct care providers and administrators in the Michigan
      aging services network to describe their work with LGBT older adults. We found
      there are very few services specific to the needs of older LGBT adults and very
      little outreach to this community. At the agency level, resistance to providing
      services was found.

PMID- 21967138
TI  - Couple meaning-making and dementia: challenges to the deficit model.
AB  - By combining a relationship- and strengths-based approach, the article suggests
      that, with the onset of progressive cognitive impairment, verbal, nonverbal, and
      embodied exchanges can function as meaning-making processes for life-partner co
      carers. These exchanges can sustain a sense of relatedness, which has been shown
      to increase wellbeing. The article identifies gaps in knowledge and practice
      limitations that result from the deficit approach to dementia research and care
      that currently dominates the field. Suggestions for future research and the
      development of interventions are included. In addition, the article challenges
      theoretical assumptions about meaning-making, arguing for a reexamination of
      dementia-affected couplehood processes.

PMID- 21967139
TI  - Residential respite care: the caregiver's last resort.
AB  - Understanding the beliefs that caregivers of people with dementia have in regard
      to the use of residential respite may inform strategies to address low service
      utilisation. In this article, the application of theory in qualitative research
      with 36 caregivers provides insight into why most delay service use. Although
      some believe that service use may increase caregiving longevity, others position
      service use in conflict with normative values, and may hold beliefs that negative
      outcomes will result from utilisation. To address caregivers' beliefs to support
      service use, improvements are required to service promotion, as well as to models
      of care.

PMID- 21967140
TI  - Perceived benefits of VFW post participation for older adults.
AB  - Older adults, as active members of the Veterans of Foreign Wars (VFW), describe
      multiple benefits of participation in the organization to their overall well
      being. This qualitative study examined the perspectives of 20 active participants
      of a VFW Post and its Ladies Auxiliary. Findings indicate that, for the study
      participants, the VFW serves as a primary source of cross-generational influence,
      emotional support, and meaningful activity and provides a safe and secure
      environment for members. This article provides valuable information that social
      work researchers and practitioners can use to help increase older adults' civic
      engagement and address service gaps.

PMID- 21967141
TI  - "Just like I'm saving money in the bank": client perspectives on care
      coordination services.
AB  - Older adults face many challenges to community living. The literature has not
      sufficiently explored the roles of care coordination in the maintenance of
      housing and access to health care among older adults, particularly from their own
      perspectives. This qualitative study analyzes the findings from 25 interviews and
      6 focus group discussions (48 participants) with a multiethnic sample of older
      adults in the New York City area. Care coordination services appear to assist
      older adults access health care, and to a lesser extent, maintain affordable
      housing. Disparities in access to care coordination appear to remain for
      immigrant, minority and suburban populations.

PMID- 21967143
TI  - Recovery after stroke: more than just walking and talking again If you don't look
      for it, you won't find it.

PMID- 21967144
TI  - Determination of the utility of the Intubation Difficulty Scale for use with
      indirect laryngoscopes.
AB  - The purpose of this study was to determine whether the Intubation Difficulty
      Scale is meaningful when used with indirect laryngoscopes. Data were analysed
      from previously published clinical trials from our group that compared the
      indirect laryngoscopes with the Macintosh laryngoscope. For each laryngoscope
      type, the Intubation Difficulty Scale score obtained for each tracheal intubation
      was correlated with data for duration of the intubation attempt and with the user
      rated difficulty of the intubation attempt. The strengths of the correlations
      between these indices were then compared for tracheas intubated with the
      Macintosh vs the indirect laryngoscopes. The Intubation Difficulty Scale
      performed well when compared with data for duration and user rated difficulty of
      the intubation attempts for the both direct and indirect laryngoscopy. However,
      the correlation between the Intubation Difficulty Scale score and both user rated
      difficulty (p = 0.001) and the duration of tracheal intubation (p = 0.003) were
      significantly stronger for the Macintosh laryngoscope compared with the indirect
      laryngoscopes. In contrast, the correlation between user rated difficulty scores
      and the data for duration of tracheal intubation was not different between the
      device types. The Intubation Difficulty Scale performs less well with indirect
      laryngoscopes than with the Macintosh laryngoscope. These findings suggest the
      need for caution with the use of this score with indirect laryngoscopes.

PMID- 21967145
TI  - Linking knowledge to action in collaborative conservation.
AB  - Authors have documented a "research-implementation gap" in conservation. Research
      intended to inform conservation practice often does not, and practice often is
      not informed by the best science. We used the literature on policy learning
      (i.e., literature attributing policy change to learning) to structure a study of
      how practice is informed by science in collaborative conservation. We studied
      implementation by U.S. states of state wildlife action plans. On the basis of 60
      interviews with government and nongovernmental organization representatives, we
      identified 144 implementation initiatives for State Wildlife Action Plans that
      were collaborative. We conducted case studies of 6 of these initiatives, which
      included interviews of key individuals and analysis of written documents. We
      coded interview transcripts and written documents to identify factors that
      influence availability and use of scientific information. We integrated these
      factors into a model of collaborative conservation. Although tangible factors
      such as funding and labor directly affected the availability of scientific
      information, practitioners' ability and willingness to use the information
      depended on less tangible factors such as the quality of interpersonal
      relationships and dialogue. Our work demonstrates empirically that relationships
      and dialogue led to: (1) the sharing of resources, such as funding and labor,
      that were needed to carry out research and produce information and (2) agreement
      among researchers and practitioners on conservation objectives, which was
      necessary for that new information to inform action. Our findings can be
      understood in the context of broader concepts articulated in the policy-learning
      literature, which establishes that social learning (improving relationships and
      dialogue) provides the foundation for conceptual learning (setting objectives)
      and technical learning (determining how to achieve these objectives).

PMID- 21967146
TI  - Histone deacetylase inhibitors from Burkholderia thailandensis.
AB  - Bioactivity-guided fractionation of an extract of  Burkholderia thailandensis 
      led to the isolation and identification of a new cytotoxic depsipeptide and its
      dimer. Both compounds potently inhibited the function of histone deacetylases 1
      and 4. The monomer, spiruchostatin C (2), was tested side by side with the
      clinical depsipeptide FK228 (1, Istodax, romidepsin) in a murine hollow fiber
      assay consisting of 12 implanted tumor cell lines. Spiruchostatin C (2) showed
      good activity toward LOX IMVI melanoma cells and NCI-H522 non small cell lung
      cancer cells. Overall, however, FK228 (1) showed a superior in vivo antitumor
      profile in comparison to the new compound.

PMID- 21967147
TI  - Delayed systemic toxicity and extensive cutaneous necrosis due to suicidal
      injection of organophosphate pesticide.

PMID- 21967148
TI  - Computational methods to calculate accurate activation and reaction energies of
      1,3-dipolar cycloadditions of 24 1,3-dipoles.
AB  - Theoretical calculations were performed on the 1,3-dipolar cycloaddition
      reactions of 24 1,3-dipoles with ethylene and acetylene. The 24 1,3-dipoles are
      of the formula X=Y(+)-Z(-) (where X is HC or N, Y is N, and Z is CH(2), NH, or O)
      or X?Y(+)-Z(-) (where X and Z are CH(2), NH, or O and Y is NH, O, or S). The high
      accuracy G3B3 method was employed as the reference. CBS-QB3, CCSD(T)//B3LYP, SCS
      MP2//B3LYP, B3LYP, M06-2X, and B97-D methods were benchmarked to assess their
      accuracies and to determine an accurate method that is practical for large
      systems. Several basis sets were also evaluated. Compared to the G3B3 method, CBS
      QB3 and CCSD(T)/maug-cc-pV(T+d)Z//B3LYP methods give similar results for both
      activation and reaction enthalpies (mean average deviation, MAD, < 1.5 kcal/mol).
      SCS-MP2//B3LYP and M06-2X give small errors for the activation enthalpies (MAD <
      1.5 kcal/mol), while B3LYP has MAD = 2.3 kcal/mol. SCS-MP2//B3LYP and B3LYP give
      the reasonable reaction enthalpies (MAD < 5.0 kcal/mol). The B3LYP functional
      also gives good results for most 1,3-dipoles (MAD = 1.9 kcal/mol for 17 common
      1,3-dipoles), but the activation and reaction enthalpies for ozone and sulfur
      dioxide are difficult to calculate by any of the density functional methods.

PMID- 21967149
TI  - Quantitative proteomic analysis revealed lovastatin-induced perturbation of
      cellular pathways in HL-60 cells.
AB  - Lovastatin, a member of the statin family of drugs, is widely prescribed for
      treating hypercholesterolemia. The statin family of drugs, however, also shows
      promise for cancer treatment and prevention. Although lovastatin is known to be
      an inhibitor for HMG-CoA reductase, the precise mechanisms underlying the drug's
      antiproliferative activity remain unclearly defined. Here we utilized mass
      spectrometry, in conjunction with stable isotope labeling by amino acids in cell
      culture (SILAC), to analyze the perturbation of protein expression in HL-60 cells
      treated with lovastatin. We were able to quantify ~3200 proteins with both
      forward and reverse SILAC labeling experiments, among which ~120 exhibited
      significant alterations in expression levels upon lovastatin treatment. Apart
      from confirming the expected inhibition of the cholesterol biosynthesis pathway,
      our quantitative proteomic results revealed that lovastatin perturbed the
      estrogen receptor signaling pathway, which was manifested by the diminished
      expression of estrogen receptor alpha, steroid receptor RNA activator 1, and
      other related proteins. Lovastatin also altered glutamate metabolism through down
      regulation of glutamine synthetase and gamma-glutamylcysteine synthetase.
      Moreover, lovastatin treatment led to a marked down-regulation of carbonate
      dehydratase II (a.k.a. carbonic anhydrase II) and perturbed the protein
      ubiquitination pathway. Together, the results from the present study underscored
      several new cellular pathways perturbed by lovastatin.

PMID- 21967150
TI  - Ubiquitous detection of gram-positive bacteria with bioorthogonal
      magnetofluorescent nanoparticles.
AB  - The ability to rapidly diagnose gram-positive pathogenic bacteria would have far
      reaching biomedical and technological applications. Here we describe the
      bioorthogonal modification of small molecule antibiotics (vancomycin and
      daptomycin), which bind to the cell wall of gram-positive bacteria. The bound
      antibiotics conjugates can be reacted orthogonally with tetrazine-modified
      nanoparticles, via an almost instantaneous cycloaddition, which subsequently
      renders the bacteria detectable by optical or magnetic sensing. We show that this
      approach is specific, selective, fast and biocompatible. Furthermore, it can be
      adapted to the detection of intracellular pathogens. Importantly, this strategy
      enables detection of entire classes of bacteria, a feat that is difficult to
      achieve using current antibody approaches. Compared to covalent nanoparticle
      conjugates, our bioorthogonal method demonstrated 1-2 orders of magnitude greater
      sensitivity. This bioorthogonal labeling method could ultimately be applied to a
      variety of other small molecules with specificity for infectious pathogens,
      enabling their detection and diagnosis.

PMID- 21967151
TI  - Laminin receptor-targeted etoposide loaded polymeric micelles: a novel approach
      for the effective treatment of tumor metastasis.
AB  - BACKGROUND: Tumor-targeted delivery is a desirable approach to improve
      therapeutic outcome of anticancer drug due to enhanced efficacy and reduced
      toxicity. PURPOSE: The present study was aimed to target laminin receptor over
      expressed tumor cells using YIGSR (Tyr-Ile-Gly-Ser-Arg) conjugated etoposide
      loaded micelles in the treatment of metastasis. METHODS: YIGSR conjugated
      micelles prepared using synthesized carboxyl and methoxy terminated poly(ethylene
      glycol)-b-poly(epsilon-caprolactone) block copolymers were evaluated for it
      efficacy against highly metastatic B16F10 cell lines conducting cytotoxicity,
      colony formation, cell migration, cellular uptake and flow cytometry studies. The
      in-vivo antimetastatic effect of micelles was evaluated using experimental
      metastatic model on C57BL/6 mice. RESULTS: YIGSR conjugated micelles of particle
      size 45.2+/-3.77 nm and zeta potential of-5.7+/-1.3 mV demonstrated enhanced
      cytotoxicity and cellular uptake with significant reduction in colony formation
      and cell migration activities compared to non-conjugated micelles. Furthermore, a
      markedly inhibition in lung colony formation was observed with these micelles.
      DISCUSSION: An enhanced cellular internalization of YIGSR conjugated micelles due
      to laminin receptor based endocytosis resulted in to higher cytotoxicity as well
      as antimetastatic effect against highly metastatic B16F10 cells. CONCLUSION:
      These studies indicate that YIGSR conjugated nanocarrier can be a promising
      approach in the treatment of tumor metastasis.

PMID- 21967152
TI  - Non-invasive temperature measurement by using phase changes in electromagnetic
      waves in a cavity resonator.
AB  - PURPOSE: To improve the efficacy of hyperthermia treatment, a novel method of non
      invasive measurement of changes in body temperature is proposed. The proposed
      method is based on phase changes with temperature in electromagnetic waves in a
      heating applicator and the temperature dependence of the dielectric constant. An
      image of the temperature change inside a body is reconstructed by applying a
      computed tomography algorithm. This method can be combined easily with a heating
      applicator based on a cavity resonator and can be used to treat cancer
      effectively while non-invasively monitoring the heating effect. In this paper the
      phase change distributions of electromagnetic waves with temperature changes are
      measured experimentally, and the accuracy of reconstruction is discussed.
      MATERIALS AND METHODS: The phase change distribution is reconstructed by using a
      prototype system with a rectangular aluminum cavity resonator that can be rotated
      360 degrees  around an axis of rotation. To make measurements without disturbing
      the electromagnetic field distribution, an optical electric field sensor is used.
      The phase change distribution is reconstructed from 4-projection data by using a
      simple back-projection algorithm. RESULTS: The paper demonstrates that the phase
      change distribution can be reconstructed. The difference between phase changes
      obtained experimentally and by numerical analysis is about 20% and is related
      mainly to the limited signal detection sensitivity of electromagnetic waves.
      CONCLUSIONS: A temperature change inside an object can be reconstructed from the
      measured phase changes in a cavity resonator.

PMID- 21967154
TI  - Dinuclear [Co(II)(NCMe)5Co(II)(NCS)4] possessing octahedral and tetrahedral
      Co(II) sites.
AB  - The structural and magnetic properties of dinuclear
      [Co(II)(NCMe)(5)Co(II)(NCS)(4)].MeCN have been investigated. The structure
      consists of an octahedral Co(II)(NCMe)(5) center connected to a tetrahedral
      Co(II)(NCS)(4) center bridged by a MU(1,3)-NCS(-) ligand. The bridging NCS(-)
      weakly couples the pair of S = (3)/(2) Co(II) spin sites, as evidenced by the
      magnetic data being best fit by the Curie-Weiss expression with theta = -15.5 K.

PMID- 21967153
TI  - Post-transcriptional regulation of IGF1R by key microRNAs in long-lived mutant
      mice.
AB  - Long-lived mutant mice, both Ames dwarf and growth hormone receptor gene
      disrupted or knockout strains, exhibit heightened cognitive robustness and
      altered IGF1 signaling in the brain. Here, we report, in both these long-lived
      mice, that three up-regulated lead microRNAs, miR-470, miR-669b, and miR-681, are
      involved in posttranscriptional regulation of genes pertinent to growth
      hormone/IGF1 signaling. All three are most prominently localized in the
      hippocampus and correspond to reduced expression of key IGF1 signaling genes:
      IGF1, IGF1R, and PI3 kinase. The decline in these genes' expression translates
      into decreased phosphorylation of downstream molecules AKT and FoxO3a. Cultures
      transfected with either miR-470, miR-669b, or miR-681 show repressed endogenous
      expression of all three genes of the IGF1 signaling axis, most significantly
      IGF1R, while other similarly up-regulated microRNAs, including let-7g and miR
      509, do not induce the same levels of repression. Transduction study in IGF1
      responsive cell cultures shows significantly reduced IGF1R expression, and AKT to
      some extent, most notably by miR-681. This is accompanied by decreased levels of
      downstream phosphorylated forms of AKT and FoxO3a upon IGF1 stimulation.
      Suppression of IGF1R by the three microRNAs is further validated by IGF1R 3'UTR
      reporter assays. Taken together, our results suggest that miR-470, miR-669b, and
      miR-681 are all functionally able to suppress IGF1R and AKT, two upstream genes
      controlling FoxO3a phosphorylation status. Their up-regulation in growth hormone
      signaling-deficient mutant mouse brain suggests reduced IGF1 signaling at the
      posttranscriptional level, for numerous gains of neuronal function in these long
      lived mice.

PMID- 21967155
TI  - Granulocyte-colony stimulating factor use and medical costs after initial
      adjuvant chemotherapy in older patients with early-stage breast cancer.
AB  - BACKGROUND: Granulocyte-colony stimulating factor (G-CSF) reduces the risk of
      severe neutropenia associated with chemotherapy, but its cost implications
      following chemotherapy are unknown. OBJECTIVE: Our objective was to examine
      associations between G-CSF use and medical costs after initial adjuvant
      chemotherapy in early-stage (stage I-III) breast cancer (ESBC). METHODS: Women
      diagnosed with ESBC from 1999 to 2005, who had an initial course of chemotherapy
      beginning within 180 days of diagnosis and including >=1 highly myelosuppressive
      agent, were identified from the Surveillance, Epidemiology, and End Results
      (SEER)-Medicare database. Medicare claims were used to describe the initial
      chemotherapy regimen according to the classes of agents used: anthracycline ([A]:
      doxorubicin or epirubicin); cyclophosphamide (C); taxane ([T]: paclitaxel or
      docetaxel); and fluorouracil (F). Patients were classified into four study groups
      according to their G-CSF use: (i) primary prophylaxis, if the first G-CSF claim
      was within 5 days of the start of the first chemotherapy cycle; (ii) secondary
      prophylaxis, if the first claim was within 5 days of the start of the second or
      subsequent cycles; (iii) G-CSF treatment, if the first claim occurred outside of
      prophylactic use; and (iv) no G-CSF. Patients were described by age, race, year
      of diagnosis, stage, grade, estrogen (ER) and progesterone (PR) receptor status,
      National Cancer Institute (NCI) Co-morbidity Index, chemotherapy regimen and G
      CSF use. Total direct medical costs ($US, year 2009 values) to Medicare were
      estimated from 4 weeks after the last chemotherapy administration up to 48
      months. Medical costs included those for ESBC treatment and all other medical
      services received after chemotherapy. Least squares regression, using inverse
      probability weighting (IPW) to account for censoring within the cohort, was used
      to evaluate adjusted associations between G-CSF use and costs. RESULTS: A total
      of 7026 patients were identified, with an average age of 72 years, of which 63%
      had stage II disease, and 59% were ER and/or PR positive. Compared with no G-CSF,
      those receiving G-CSF primary prophylaxis were more likely to have stage III
      disease (30% vs. 16%; p < 0.0001), to be diagnosed in 2003-5 (87% vs. 26%; p <
      0.0001), and to receive dose-dense AC-T (26% vs. 1%; p < 0.0001), while they were
      less likely to receive an F-based regimen (12% vs. 42%; p < 0.0001). Overall, the
      estimated average direct medical cost over 48 months after initial chemotherapy
      was $US 42,628. In multivariate analysis, stage II or III diagnosis (compared
      with stage I), NCI Co-morbidity Index score 1 or >=2 (compared with 0), or FAC or
      standard AC-T (each compared with AC) were associated with significantly higher
      IPW 48-month costs. Adjusting for patient demographic and clinical factors, costs
      in the G-CSF primary prophylaxis group were not significantly different from
      those not receiving primary prophylaxis (the other three study groups combined).
      In an analysis that included four separate study groups, G-CSF treatment was
      associated with significantly greater costs (incremental cost = $US 2938; 95% CI
      285, 5590) than no G-CSF. CONCLUSIONS: Direct medical costs after initial
      chemotherapy were not statistically different between those receiving G-CSF
      primary prophylaxis and those receiving no G-CSF, after adjusting for potential
      confounders.

PMID- 21967157
TI  - Maternal one-carbon nutrient intake and cancer risk in offspring.
AB  - Dietary intake of one-carbon nutrients, particularly folate, vitamin B(2) 
      (riboflavin), vitamin B(6) , vitamin B(12) , and choline have been linked to the
      risk of cancers of the colon and breast in both human and animal studies. More
      recently, experimental and epidemiological data have emerged to suggest that
      maternal intake of these nutrients during gestation may also have an impact on
      the risk of cancer in offspring later in life. Given the plasticity of DNA
      methylation in the developing embryo and the established role of one-carbon
      metabolism in supporting biological methylation reactions, it is plausible that
      alterations in maternal one-carbon nutrient availability might induce subtle
      epigenetic changes in the developing embryo and fetus that persist into later
      life, altering the risk of tumorigenesis throughout the lifespan. This review
      summarizes the current literature on maternal one-carbon nutrient intake and
      offspring cancer risk, with an emphasis on cancers of the colon and breast, and
      discusses specific epigenetic modifications that may play a role in their
      pathogenesis.

PMID- 21967156
TI  - Erlotinib monotherapy for the maintenance treatment of non-small cell lung cancer
      after previous platinum-containing chemotherapy: a NICE single technology
      appraisal.
AB  - The UK National Institute for Health and Clinical Excellence (NICE) invited the
      manufacturer of erlotinib (Roche) to submit evidence for the clinical and cost
      effectiveness of erlotinib as monotherapy for the maintenance treatment of
      patients with non-small cell lung cancer (NSCLC) and stable disease following
      previous treatment with four cycles of platinum-containing therapy. The Liverpool
      Reviews and Implementation Group (LRiG) at the University of Liverpool was
      commissioned to act as the Evidence Review Group (ERG) for this appraisal. The
      ERG reviewed the clinical- and cost-effectiveness evidence in two stages and in
      accordance with the decision problem defined by NICE. The analysis of the
      submitted models assessed the appropriateness of the approach taken by the
      manufacturer in modelling the decision problem. Analysis also included
      reliability of model implementation and the extent of conformity to published
      standards and prevailing norms of practice within the health economics modelling
      community. Particular attention was paid to issues likely to have substantial
      impact on the base-case cost-effectiveness results. Clinical evidence was derived
      from a multi-centre, double-blind, randomized, phase III study designed to
      address the overall population of NSCLC patients. Outcomes included progression
      free survival (PFS) and overall survival (OS). The recruited population was
      mainly from outside of Western Europe and no patients in the pivotal trial had
      received pemetrexed as a first-line therapy, which is now accepted clinical
      practice in the UK. The evidence considered in this article includes only the
      population for whom marketing authorizations has been received--that is, patients
      with stable disease following first-line therapy. The trial reported a small but
      statistically significant increase in both PFS and OS in patients with stable
      disease receiving erlotinib compared with placebo. However, no significant
      difference was identified in OS when patients with non-squamous disease and
      stable disease were considered as a subgroup. The economic evidence was focussed
      on the ERG's assessment of three economic models that related to patients with
      stable disease and compared erlotinib with placebo in the squamous and non
      squamous populations and erlotinib with pemetrexed in the non-squamous
      population. The incremental cost-effectiveness ratios (ICERs) reported by the
      manufacturer were L39,936 per QALY gained (stable disease, all); L35,491 per QALY
      gained (stable disease, squamous); and L40,020 per QALY gained (stable disease,
      non-squamous). In comparison with pemetrexed, in the cases where erlotinib was
      considered to be superior or equivalent, erlotinib dominated. In the cases where
      erlotinib was considered to be slightly inferior, then the ICERs ranged between
      L91,789 and L511,351 per QALY gained; these ICERs appear in the south-west corner
      of a cost-effectiveness plane, i.e. erlotinib is cheaper but less effective than
      pemetrexed. The ERG recalculated the base-case cost-effectiveness results in the
      manufacturer's submission, considering nine key areas where corrections and/or
      adjustments were required, related to time horizon, discounting logic, costs of
      erlotinib and pemetrexed, cost of second-line chemotherapy, unit costs, utility
      values, PFS and OS. This resulted in ERG-revised ICERs for the stable disease
      squamous population of L44,812 per QALY gained, in the stable disease non
      squamous population of L68,120 per QALY gained, and, when erlotinib was compared
      with pemetrexed, the result was L84,029 per QALY gained. All values were above
      NICE's perceived willingness-to-pay threshold. After the second Appraisal
      Committee meeting, the Committee did not recommend the use of erlotinib in this
      patient population.

PMID- 21967158
TI  - Oral contraceptive use: impact on folate, vitamin B6, and vitamin B12 status.
AB  - Since many unplanned pregnancies occur while women are using oral contraceptives
      (OCs), it is important to understand the potential impact of these drugs on
      folate, vitamin B6 , and vitamin B12 status. Although a number of early studies
      concluded that OCs negatively impact folate status, the majority of these studies
      were conducted when the estrogen content of OCs was much higher. In addition, the
      interpretation of findings from many of these studies is problematic since no
      controls were included for potentially confounding factors. The presently
      available data do not support a conclusion that currently used OCs negatively
      impact folate status. In regard to vitamin B6 , however, existing population
      based data do provide evidence that current low-dose OCs may negatively impact
      vitamin B6 status. The observed depression in plasma pyridoxal 5'-phosphate
      concentrations in OC users may reflect decreased body reserves of the vitamin,
      which could put women who discontinue OCs and become pregnant at risk for vitamin
      B6 inadequacy during pregnancy. Functional indicators of vitamin B12 status are
      not significantly impacted by OC use. Definitive conclusions, however, await
      further investigations.

PMID- 21967159
TI  - Vitamins and bone health: beyond calcium and vitamin D.
AB  - Osteoporosis is a major health disorder associated with an increased risk of
      fracture. Nutrition is among the modifiable factors that influence the risk of
      osteoporosis and fracture. Calcium and vitamin D play important roles in
      improving bone mineral density and reducing the risk of fracture. Other vitamins
      appear to play a role in bone health as well. In this review, the findings of
      studies that related the intake and/or the status of vitamins other than vitamin
      D to bone health in animals and humans are summarized. Studies of vitamin A
      showed inconsistent results. Excessive, as well as insufficient, levels of
      retinol intake may be associated with compromised bone health. Deficiencies in
      vitamin B, along with the consequent elevated homocysteine level, are associated
      with bone loss, decreased bone strength, and increased risk of fracture.
      Deficiencies in vitamins C, E, and K are also associated with compromised bone
      health; this effect may be modified by smoking, estrogen use or hormonal therapy
      after menopause, calcium intake, and vitamin D. These findings highlight the
      importance of adequate nutrition in preserving bone mass and reducing the risk of
      osteoporosis and fractures.

PMID- 21967160
TI  - Effect of diet on adiponectin levels in blood.
AB  - Dietary management has been considered an alternative means of modulating
      adiponectin levels. The purpose of this review is to examine the scientific
      evidence regarding the effect of diet on adiponectin levels in blood. Clinical
      trials were selected from Medline until April 2010 using the following MeSH
      terms: adipokines OR adiponectin AND diet OR lifestyle. A total of 220 articles
      were identified in the initial search, and 52 studies utilizing three different
      methods of dietary management were included in the present review: low-calorie
      diets (n = 9 studies), modification of diet composition (n = 33), and diet plus
      exercise (n = 10). Daily intake of fish or omega-3 supplementation increased
      adiponectin levels by 14-60%. Weight loss achieved with a low-calorie diet plus
      exercise increased adiponectin levels in the range of 18-48%. A 60-115% increase
      in adiponectin levels was obtained with fiber supplementation. In conclusion,
      dietary management can be an effective therapeutic means of increasing
      adiponectin levels. Studies investigating different forms of adiponectin and
      changes in the types of adipose tissue are necessary in order to elucidate the
      mechanisms involved in the modulation of adiponectin levels.

PMID- 21967161
TI  - Vitamin A and clefting: putative biological mechanisms.
AB  - Nutritional factors such as vitamin intake contribute to the etiology of cleft
      palate. Vitamin A is a regulator of embryonic development. Excess vitamin A can
      cause congenital malformations such as spina bifida and cleft palate. Therefore,
      preventive nutritional strategies are required. This review identifies putative
      biological mechanisms underlying the association between maternal vitamin A
      intake and cleft palate. Excessive vitamin A may disturb all three stages of
      palatogenesis: 1) during shelf outgrowth, it may decrease cell proliferation and
      thus prevent tissue development; 2) it may prevent shelf elevation by affecting
      extracellular matrix composition and hydration; and 3) during shelf fusion, it
      may affect epithelial differentiation and apoptosis, which precludes the
      formation of a continuous palate. In general, high doses of vitamin A affect
      palatogenesis through interference with cell proliferation and growth factors
      such as transforming growth factor beta and platelet-derived growth factor. The
      effects of lower doses of vitamin A need to be investigated in greater depth in
      order to improve public health recommendations.

PMID- 21967163
TI  - Characterization of pyoverdine and achromobactin in Pseudomonas syringae pv.
      phaseolicola 1448a.
AB  - BACKGROUND: Pseudomonas syringae pv. phaseolicola 1448a (P. syringae 1448a), the
      causative agent of bean halo blight, is a bacterium capable of occupying diverse
      biological niches. Under conditions of iron starvation P. syringae 1448a secretes
      siderophores for active uptake of iron. The primary siderophore of P. syringae
      1448a is pyoverdine, a fluorescent molecule that is assembled from amino acid
      precursors by non-ribosomal peptide synthetase (NRPS) enzymes. Whereas other
      species of Pseudomonas often exhibit structural variations in the pyoverdine
      produced by different strains, all P. syringae pathovars previously tested have
      been found to make an identical pyoverdine molecule. P. syringae 1448a also
      appears to have the genetic potential to make two secondary siderophores,
      achromobactin and yersiniabactin, each of which has previously been detected in
      different P. syringae pathovars. RESULTS: Five putative pyoverdine NRPS genes in
      P. syringae 1448a were characterized in-silico and their role in pyoverdine
      biosynthesis was confirmed by gene knockout. Pyoverdine was purified from P.
      syringae 1448a and analyzed by MALDI-TOF and MS/MS spectroscopy. Peaks were
      detected corresponding to the expected sizes for the pyoverdine structure
      previously found in other P. syringae pathovars, but surprisingly P. syringae
      1448a appears to also produce a variant pyoverdine species that has an additional
      71 Da monomer incorporated into the peptide side chain. Creation of pyoverdine
      null mutants of P. syringae 1448a revealed that this strain also produces
      achromobactin as a temperature-regulated secondary siderophore, but does not
      appear to make yersiniabactin. Pyoverdine and achromobactin null mutants were
      characterized in regard to siderophore production, iron uptake, virulence and
      growth in iron limited conditions. CONCLUSIONS: This study provides the first
      evidence of a P. syringae pathovar producing a side chain variant form of
      pyoverdine. We also describe novel IC50 and liquid CAS assays to quantify the
      contribution of different siderophores across a range of iron starvation
      conditions, and show that although achromobactin has potential to contribute to
      fitness its contribution is masked by the presence of pyoverdine, which is a
      significantly more effective siderophore. Neither pyoverdine nor achromobactin
      appear to be required for P. syringae 1448a to cause bean halo blight, indicating
      that these siderophores are not promising targets for crop protection strategies.

PMID- 21967165
TI  - The energetics of motivated cognition: a force-field analysis.
AB  - A force-field theory of motivated cognition is presented and applied to a broad
      variety of phenomena in social judgment and self-regulation. Purposeful cognitive
      activity is assumed to be propelled by a driving force and opposed by a
      restraining force. Potential driving force represents the maximal amount of
      energy an individual is prepared to invest in a cognitive activity. Effective
      driving force corresponds to the amount of energy he or she actually invests in
      attempt to match the restraining force. Magnitude of the potential driving force
      derives from a combination of goal importance and the pool of available mental
      resources, whereas magnitude of the restraining force derives from an
      individual's inclination to conserve resources, current task demands, and
      competing goals. The present analysis has implications for choice of means to
      achieve one's cognitive goals as well as for successful goal attainment under
      specific force-field constellations. Empirical evidence for these effects is
      considered, and the underlying theory's integrative potential is highlighted.
      (PsycINFO Database Record (c) 2012 APA, all rights reserved).

PMID- 21967164
TI  - Gene networks and haloperidol-induced catalepsy.
AB  - The current study examined the changes in striatal gene network structure induced
      by short-term selective breeding from a heterogeneous stock for haloperidol
      response. Brain (striatum) gene expression data were obtained using the Illumina
      WG 8.2 array, and the datasets from responding and non-responding selected lines
      were independently interrogated using a weighted gene coexpression network
      analysis (WGCNA). We detected several gene modules (groups of coexpressed genes)
      in each dataset; the membership of the modules was found to be largely
      concordant, and a consensus network was constructed. Further validation of the
      network topology showed that using approximately 35 samples is sufficient to
      reliably infer the transcriptome network. An in-depth analysis showed significant
      changes in network structure and gene connectivity associated with the selected
      lines; these changes were validated using a bootstrapping procedure. The most
      dramatic changes were associated with a gene module richly annotated with
      neurobehavioral traits. The changes in network connectivity were concentrated in
      the links between this module and the rest of the network, in addition to changes
      within the module; this observation is consistent with recent results in protein
      and metabolic networks. These results suggest that a network-based strategy will
      help identify the genetic factors associated with haloperidol response.

PMID- 21967167
TI  - Enhancement of field emission and photoluminescence properties of graphene-SnO2
      composite nanostructures.
AB  - In this study, the SnO(2) nanostructures and graphene-SnO(2) (G-SnO(2)) composite
      nanostructures were prepared on n-Si (100) substrates by electrophoretic
      deposition and magnetron sputtering techniques. The field emission of SnO(2)
      nanostructures is improved largely by depositing graphene buffer layer, and the
      field emission of G-SnO(2) composite nanostructures can also further be improved
      by decreasing sputtering time of Sn nanoparticles to 5 min. The photoluminescence
      (PL) spectra of the SnO(2) nanostructures revealed multipeaks, which are
      consistent with previous reports except for a new peak at 422 nm. Intensity of
      six emission peaks increased after depositing graphene buffer layer. Our results
      indicated that graphene can also be used as buffer layer acting as interface
      modification to simultaneity improve the field emission and PL properties of
      SnO(2) nanostructures effectively.

PMID- 21967166
TI  - Heart rate variability and exercise in aging women.
AB  - BACKGROUND: Our group has shown a positive dose-response in maximal
      cardiorespiratory exercise capacity (VO(2max)) and heart rate variability (HRV)
      to 6 months of exercise training but no improvement in VO(2max) for women >=60
      years. Here, we examine the HRV response to exercise training in postmenopausal
      women younger and older than 60 years. METHODS: We examined 365 sedentary,
      overweight, hypertensive, postmenopausal women randomly assigned to sedentary
      control or exercise groups exercising at 50% (4 kcal/kg/week, [KKW]), 100% (8
      KKW) and 150% (12 KKW) of the National Institutes of Health (NIH) Consensus
      Development Panel physical activity guidelines. Primary outcomes included time
      and frequency domain indices of HRV. RESULTS: Overall, our analysis demonstrated
      a significant improvement in parasympathetic tone (rMSSD and high frequency
      power) for both age strata at 8 KKW and 12 KKW. For rMSSD, the age-stratified
      responses were: control, <60 years, 0.20 ms, 95% confidence interval (CI)-2.40,
      2.81; >=60 years, 0.07 ms, 95% CI -3.64, 3.79; 4 KKW, <60 years, 3.67 ms, 95% CI
      1.55, 5.79; >=60 years, 1.20 ms, 95% CI -1.82, 4.22; 8-KKW, <60 years, 3.61 ms,
      95% CI 0.88, 6.34; >=60 years, 5.75 ms, 95% CI 1.89, 9.61; and 12-KKW, <60 years,
      5.07 ms, 95% CI 2.53, 7.60; >=60 years, 4.28 ms, 95% CI 0.42, 8.14. CONCLUSIONS:
      VO(2max) and HRV are independent risk factors for cardiovascular disease (CVD)
      mortality. Despite no improvement in VO(2max), parasympathetic indices of HRV
      increased in women >=60 years. This is clinically important, as HRV has important
      CVD risk and neurovisceral implications beyond cardiorespiratory function.

PMID- 21967168
TI  - Tailoring the vapor-liquid-solid growth toward the self-assembly of GaAs nanowire
      junctions.
AB  - New insights into understanding and controlling the intriguing phenomena of
      spontaneous merging (kissing) and the self-assembly of monolithic Y- and T
      junctions is demonstrated in the metal-organic chemical vapor deposition growth
      of GaAs nanowires. High-resolution transmission electron microscopy for
      determining polar facets was coupled to electrostatic-mechanical modeling and
      position-controlled synthesis to identify nanowire diameter, length, and pitch,
      leading to junction formation. When nanowire patterns are designed so that the
      electrostatic energy resulting from the interaction of polar surfaces exceeds the
      mechanical energy required to bend the nanowires to the point of contact, their
      fusion can lead to the self-assembly of monolithic junctions. Understanding and
      controlling this phenomenon is a great asset for the realization of dense arrays
      of vertical nanowire devices and opens up new ways toward the large scale
      integration of nanowire quantum junctions or nanowire intracellular probes.

PMID- 21967169
TI  - Tracking speech sound acquisition.
AB  - This article describes a procedure to aid in the clinical appraisal of child
      speech. The approach, based on the work by Dinnsen, Chin, Elbert, and Powell
      (1990; Some constraints on functionally disordered phonologies: Phonetic
      inventories and phonotactics. Journal of Speech and Hearing Research, 33, 28-37),
      uses a railway idiom to track gains in the complexity of speech sound production.
      A clinical case study is reviewed to illustrate application of the procedure. The
      procedure is intended to facilitate application of an evidence-based procedure to
      the clinical management of developmental speech sound disorders.

PMID- 21967170
TI  - Serratia marcescens strains implicated in adverse transfusion reactions form
      biofilms in platelet concentrates and demonstrate reduced detection by automated
      culture.
AB  - BACKGROUND AND OBJECTIVES: Serratia marcescens is a gram-negative bacterium that
      has been implicated in adverse transfusion reactions associated with contaminated
      platelet concentrates. The aim of this study was to investigate whether the
      ability of S. marcescens to form surface-attached aggregates (biofilms) could
      account for contaminated platelet units being missed during screening by the
      BacT/ALERT automated culture system. MATERIALS AND METHODS: Seven S. marcescens
      strains, including biofilm-positive and biofilm-negative control strains and five
      isolates recovered from contaminated platelet concentrates, were grown in
      enriched Luria-Bertani medium and in platelets. Biofilm formation was examined by
      staining assay, dislodging experiments and scanning electron microscopy. Clinical
      strains were also analysed for their ability to evade detection by the BacT/ALERT
      system. RESULTS: All strains exhibited similar growth in medium and platelets.
      While only the biofilm-positive control strain formed biofilms in medium, this
      strain and three clinical isolates associated with transfusion reactions formed
      biofilms in platelet concentrates. The other two clinical strains, which had been
      captured during platelet screening by BacT/ALERT, failed to form biofilms in
      platelets. Biofilm-forming clinical isolates were approximately three times
      (P<0.05) more likely to be missed by BacT/ALERT screening than biofilm-negative
      strains. CONCLUSION: S. marcescens strains associated with transfusion reactions
      form biofilms under platelet storage conditions, and initial biofilm formation
      correlates with missed detection of contaminated platelet concentrates by the
      BacT/ALERT system.

PMID- 21967171
TI  - Evaluation of left atrial function in patients with coronary artery disease by
      two-dimensional strain and strain rate imaging.
AB  - BACKGROUND: Left ventricular (LV) dysfunction in patients with coronary artery
      disease is shown by strain and strain rate imaging. However, left atrium (LA)
      function in patients with coronary artery disease (CAD) has not been assessed by
      this method. METHODS AND RESULTS: In 34 CAD patients, including 17 patients with
      enlarged LA (LA diameter <= 4.0 cm) and 17 with normal-size LA (LA diameter <=
      4.0 cm), two-dimensional strain echocardiographic imaging (2DSE) was performed.
      Twenty healthy subjects as a control group were included. Both conventional
      parameters and strain parameters, such as LA peak systolic strain (LAs S/SR),
      preatrial contraction strain (LAa S), peak systolic (LAs SR), early diastolic
      strain rate (LAe SR) and late diastolic strain rate (LAa SR), were measured.
      Conventional parameters were abnormal in CAD patients with enlarged LA (ELA), but
      there were no significant differences between CAD with normal-size left atrium
      (NLA) and control groups. LAs S/SR and LAe SR were lower in patients than in
      normal controls, and were even lower in CAD-ELA group (P < 0.05). LAa S/SR were
      lower in CAD patients with ELA (P < 0.05), but without a significant difference
      between CAD-NLA and control groups. A significant correlation was observed
      between LAs S/SR and LA emptying fraction (r = 0.85, P < 0.05; r = 0.72, P <
      0.05, respectively). LAa S/SR related well to LA ejection fraction (r = 0.68, P <
      0.05; r = 0.61, P < 0.05, respectively). LAs SR was most accurate in identifying
      both CAD patients with NLA from controls and CAD patients from controls (area
      under the curve: 0.91; 0.95, respectively). CONCLUSIONS: LA diastolic dysfunction
      occurs prior to LA systolic dysfunction in CAD patients, and LAs SR is the most
      accurate index in identifying patients with CAD.

PMID- 21967176
TI  - Trauma therapy for death row families.
AB  - The family members of death row inmates undergo unique suffering that includes
      disenfranchised grief and intense psychological trauma. In Texas, where
      executions occur at a rate of 1 every 2 weeks, this class of trauma victims
      presumably is large, a fact that should generate public mental health concern.
      Yet the class remains virtually unknown to the therapeutic community. Very little
      has been done to address the trauma healing needs of death row families. This
      theoretical paper proposes that structural therapy designed to reengage
      attachment relationships and reempower family members' innate resources to
      emotionally regulate one another may provide one of the most effective means of
      helping this population survive trauma.

PMID- 21967177
TI  - Understanding maltreating mothers: a synthesis of relational trauma, attachment
      disorganization, structural dissociation of the personality, and experiential
      avoidance.
AB  - Treatment options are limited for families in which the child has severe and
      intractable disturbances of emotion and behavior, in which there is suspected or
      confirmed maltreatment by the mother, and in which the mother has her own history
      of childhood neglect and abuse. This paper proposes a model for understanding
      maltreatment in mother-child dyads, drawing upon the developmental
      psychopathology, behavior, and trauma literatures. At the core of this model is
      the hypothesis that a mother's maltreating behavior arises from unconscious
      attempts to experientially avoid the reemergence of an attachment-related
      dissociative part of the personality that contains the distress arising from her
      own early experiences of attachment relationships. The implications of this model
      for therapy are considered.

PMID- 21967178
TI  - Developing a trauma-informed, emergency department-based intervention for victims
      of urban violence.
AB  - The Surgeon General's report on youth violence, the Centers for Disease Control
      and Prevention, and other national organizations are calling for public health
      approaches to the issue of youth violence. Hospital-based violence intervention
      programs have shown promise in reducing recurrent violence and decreasing future
      involvement in the criminal justice system. These programs seldom address trauma
      related symptoms. We describe a conceptual framework for emergency department
      based and hospital-based violence intervention programs that intentionally
      addresses trauma. The intervention described--Healing Hurt People--is a trauma
      informed program designed to intervene in the lives of injured patients at the
      life-changing moment of violent injury. This community-focused program seeks to
      reduce recurrent violence among 8- to 30-year-olds through opportunities for
      healing and connection. Healing Hurt People considers the adversity that patients
      have experienced during their lives and seeks to break the cycle of violence by
      addressing this trauma.

PMID- 21967179
TI  - Somatoform and psychoform dissociation among women with orgasmic and sexual pain
      disorders.
AB  - Since the 20th century, psychogenic female sexual dysfunctions (FSD), like some
      somatoform and conversion disorders, have been considered an expression of
      somatoform dissociation. Several studies have reported dissociative symptoms in
      different somatoform and conversion disorders, but limited data are available on
      dissociation among patients with FSD. The aim of this study was to assess
      somatoform and psychoform dissociation among patients with women's orgasmic
      disorder, dyspareunia, and vaginismus. A battery of self-administered
      questionnaires (Somatoform Dissociation Questionnaire, Dissociative Experiences
      Scale, Hospital Anxiety and Depression Scale, Impact of Event Scale-Revised) was
      given to 200 gynecological outpatients to assess psychoform and somatoform
      dissociation and their association with FSD. A strong association between
      somatoform dissociation and FSD was observed (adjusted odds ratio [OR] = 5.39,
      95% confidence interval [CI] = 1.15-25.32), the association between somatoform
      and psychoform dissociation being estimated by an adjusted OR of 4.83 (95% CI =
      1.17-19.91). Our results are compatible with the idea that some forms of FSD
      could be regarded as somatoform dissociative disorders.

PMID- 21967180
TI  - Depersonalization as a mediator in the relationship between self-focused
      attention and auditory hallucinations.
AB  - The purpose of this work was to study the potentially mediating role of certain
      dissociative factors, such as depersonalization, between self-focused attention
      and auditory hallucinations. A total of 59 patients diagnosed with schizophrenic
      disorder completed a self-focused attention scale ( M. F. Scheier & C. S. Carver,
      1985 ), the Cambridge Depersonalization Scale (M. Sierra & G. E. Berrios, 2000),
      and the hallucination and delusion items on the Positive and Negative Syndrome
      Scale (S. R. Kay, L. A. Opler, & J. P. Lindenmayer, 1988). The results showed
      that self-focused attention correlated positively with auditory hallucinations,
      with delusions, and with depersonalization. It was also demonstrated that
      depersonalization has a mediating role between self-focused attention and
      auditory hallucinations but not delusions. In the discussion, the importance of
      dissociative processes in understanding the formation and maintenance of auditory
      hallucinations is suggested.

PMID- 21967181
TI  - The problem with pleasure: part II. The research.
AB  - This study explores how adult survivors of chronic abuse and neglect define
      pleasure, the disruption of pleasure, and the repair of the capacity for pleasure
      in the context of the therapeutic relationship. Using narrative methodology, I
      interviewed 15 clinical pairs of patients and their therapists separately.
      Thematic analysis revealed 8 findings. All patients reported the capacity to
      experience pleasure throughout life prior to therapy. Subjects defined pleasure
      as a variety of positive affects that fell into 2 categories: pleasure in
      activities and interests and pleasure in relationships. All patients reported a
      history of traumatic disruption of pleasure in childhood. Patients reported a
      history of internalizing and reenacting their own disruption of pleasure.
      Narratives of the patients were consistent with the narratives told by the
      therapists. In many clinical pairs, both parties spoke positively of an important
      therapeutic event when the therapist stepped out of his or her usual treatment
      frame. Safety, consistency, reliability, predictability, and compassionate caring
      were spoken of throughout the sample as elements that created a pleasurable and
      therapeutically reparative relationship. Patients spoke repeatedly of the
      importance of "finding a self" to the experience of pleasure. Pleasure enhanced
      the ability to find a self, and finding a self enhanced patients' capacity for
      pleasure. This study invites further research to investigate the function of
      pleasure in the process of therapeutic repair for chronically traumatized
      populations.

PMID- 21967190
TI  - Mechanically induced scission and subsequent thermal remending of
      perfluorocyclobutane polymers.
AB  - Perfluorocyclobutane (PFCB) polymer solutions were subjected to pulsed
      ultrasound, leading to mechanically induced chain scission and molecular weight
      degradation. (19)F NMR revealed that the new, mechanically generated end groups
      are trifluorovinyl ethers formed by cycloreversion of the PFCB groups, a process
      that differs from thermal degradation pathways. One consequence of the
      mechanochemical process is that the trifluorovinyl ether end groups can be
      remended simply by subjecting the polymer solution to the original polymerization
      conditions, that is, heating to >150  degrees C. Stereochemical changes in the
      PFCBs, in combination with radical trapping experiments, indicate that PFCB
      scission proceeds via a stepwise mechanism with a 1,4-diradical intermediate,
      offering a potential mechanism for localized functionalization and cross-linking
      in regions of high stress.

PMID- 21967191
TI  - Treatment of articulatory dysfunction in Parkinson's disease using repetitive
      transcranial magnetic stimulation.
AB  - BACKGROUND AND PURPOSE: Neuroimaging has demonstrated that improved speech
      outcomes in Parkinson's Disease (PD) subsequent to behavioural treatment
      approaches are associated with increased activity in the motor and pre-motor
      cortex. High-frequency repetitive transcranial magnetic stimulation (rTMS) is
      capable of modulating cortical activity and has been reported to have significant
      benefit to general motor function in PD. It is possible that high-frequency rTMS
      may also have beneficial outcomes on speech production in PD. METHODS: High
      frequency (5 Hz) rTMS was applied to 10 active stimulation and 10 sham placebo
      patients for 10 min/day (3000 pulses), for 10 days and speech outcome measures
      and lingual kinematic parameters recorded at baseline and 1 week, 2 and 12 months
      post-stimulation. RESULTS: The findings demonstrated positive treatment-related
      changes observed in the active rTMS group when compared to the sham placebo
      control group at 2 and 12 months post-stimulation in speech intelligibility,
      communication efficiency ratio, maximum velocity of tongue movements and distance
      of tongue movements. CONCLUSION: The results support the use of high-frequency
      rTMS as a therapeutic tool for the treatment of articulatory dysfunction in PD.

PMID- 21967192
TI  - Wilhelm Fabry's 1614 report on a giant condyloma of the penis.
AB  - For many years it has been the work of Buschke and Lowenstein that has justified
      calling the exophytic, locally destructive tumour of the anogenital mucosal
      surface 'giant condyloma of Buschke and Lowenstein' or GCBL. In order to
      investigate the early history of this rare disease we examined the writings of
      the barber-surgeon Wilhelm Fabry (1560-1634) who had a serious interest in
      dermatological disorders and their treatment. We analysed Fabry's 600 Latin case
      reports and identified the case of a 'monstrous penile tumour'. We then
      translated this text into English and compared it point by point with later
      publications. This was followed by a cursory review of surgical treatises from
      the 16th to the 18th centuries. In 1614 Fabry described and depicted a tumour of
      the penis; the clinical characteristics (gradual formation of a warty lesion,
      considerable size, invasive growth, absence of metastases) indicated it was a
      giant condyloma. His mention of the urethral fistulization enables discrimination
      from 'common' condylomata acuminata, and the survival period of 10 years after
      amputation allows exclusion of a 'true' carcinoma. This report is singular among
      17th-century case histories. The neoplasias described 300 years later are most
      probably biologically identical. Thus, Fabry's is the first clinical report; the
      histological classification, however, belongs to Buschke and Lowenstein. From now
      on the disease should be designated with the eponym giant condyloma of Fabry
      Buschke-Lowenstein or GCFBL.

PMID- 21967193
TI  - Health risks of using mothballs in Greater Accra, Ghana.
AB  - OBJECTIVE: Internal use of 'camphor' is a potential public health concern in
      Accra. We sought to identify the toxins being sold as mothballs in Greater Accra
      and use this information to help educate both clinicians and the public. METHODS:
      Mothballs are commonly sold by street and marketplace vendors in unmarked cling
      film-wrapped packs. Fifteen small packs of mothballs were purchased from random
      vendors in three major markets and six roadside stands in Greater Accra. All
      samples were subjected to the float test; one sample was confirmed by gas
      chromatography/mass spectroscopy. RESULTS: All samples sank in tap water but
      floated in a saturated salt solution, consistent with naphthalene. The analysed
      sample was identified as naphthalene. CONCLUSION: Naphthalene was most likely the
      primary ingredient in all the mothballs purchased for the study. Naphthalene is
      poorly soluble in water, and 'camphor water' is unlikely to cause harm. However,
      ideas about the efficacy of 'camphor' as a purification tool may lead to
      therapeutic misuse by analogy. A high prevalence of G6PD in the Ghanaian
      population may increase the risk of toxic haematologic effects from ingestion of
      mothballs. Mothballs known in Greater Accra as 'camphor' are likely to be
      predominantly naphthalene. A public awareness campaign about the health risks of
      mothball ingestion is planned.

PMID- 21967194
TI  - Theoretical design of a light-driven molecular rotary motor with low energy
      helical inversion: 9-(5-methyl-2-phenyl-2-cyclopenten-1-ylidene)-9H-fluorene.
AB  - A light-driven molecular rotary motor of 9-(5-methyl-2-phenyl-2-cyclopenten-1
      ylidene)-9H-fluorene (MPCPF) has been designed by means of ab initio complete
      active space self-consistent field and its second order multireference Moller
      Plesset perturbation methods. In the present model molecule of MPCPF, 9H-fluorene
      (as a stator) and 5-methyl-2-phenyl-2-cyclopenten-1-ylidene (as a rotor) are
      directly linked with each other by a C?C double bond. Even by a substitution of
      phenyl group, MPCPF comes to have a stable P-helical MPCPF and a metastable M
      helical MPCPF, and exhibits unidirectionality around the C?C double bond. In
      addition, interchange of the helicity can proceed with a low energy barrier
      through a floppy phenyl torsional motion. This is in contrast to previous light
      driven molecular rotary motors where the unidirectionality is ensured by rigid
      and sterically overcrowded rotors. In the full rotary process of MPCPF,
      therefore, constancy of the rotation speed is expected to be much more improved
      as well as unidirectionality.

PMID- 21967195
TI  - Detection of tumor necrosis factor-alpha and interleukin-6 in exhaled breath
      condensate of rats with pneumonia due to staphylococcal enterotoxin B.
AB  - Exhaled breath condensate (EBC) may contain mediators of acute lung injury. The
      objectives were to determine if EBC could be collected in a mechanically
      ventilated rat, to measure tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-6 (IL-6) in the EBC after staphylococcal enterotoxin B administration
      (SEB) and to find out if the concentrations of TNF-alpha and IL-6 correlated with
      those in lung lavage. Four hours after SEB instillation, rats were placed on
      mechanical ventilation and EBC was collected over 90 minutes. Lung lavage was
      collected and white cell count was determined. TNF-alpha and IL-6 were measured
      in the EBC and lavage. EBC was available in a sufficient quantity (250-400 MUL)
      for the measurement of cytokines. The rats that received SEB had an inflammatory
      response when compared to control rats as shown by an increase in white cell
      count. TNF-alpha and IL-6 were detected in the EBC. Concentration of TNF-alpha
      correlated with that in the lavage (r = .497, P = .021), whereas IL-6 did not.
      EBC can be collected in rats in sufficient quantities to study acute lung injury.
      TNF-alpha and IL-6 can be measured in the EBC. Correlation between TNF-alpha in
      the EBC and lavage was demonstrated in this rat model of lung injury.

PMID- 21967196
TI  - Aerosolized recombinant human lysozyme enhances the bactericidal effect of
      tobramycin in a hamster model of Pseudomonas aeruginosa-induced pneumonia.
AB  - Previous studies from this laboratory have shown that aerosolized recombinant
      human lysozyme (rhLZ) mitigates Pseudomonas aeruginosa (PA)-induced pneumonia. In
      the current investigation, our laboratory tested the hypothesis that aerosolized
      rhLZ can potentiate the effects of tobramycin (TBMN), thereby reducing the
      effective dose of this agent in the treatment of PA-induced pneumonia. Syrian
      hamsters were instilled intratracheally with PA, then exposed to an aerosol
      containing either 1% rhLZ, 3 MUg TBMN, or a combination of both agents. In
      contrast to the initial studies with rhLZ, which involved 3 separate aerosol
      exposures, only a single treatment was used in the current investigation. Twenty
      four hours after completion of the aerosol regimen, the following parameters were
      measured: (1) whole-lung colony-forming units (CFU), (2) total bronchoalveolar
      lavage fluid (BALF) CFU, (3) lung histopathology, and (4) total BALF neutrophils.
      The combination of rhLZ and TBMN significantly reduced whole-lung and BALF CFU,
      as well as the inflammatory index, compared to TBMN alone. Similar results were
      seen in vitro with regard to bactericidal activity. These findings provide a
      rationale for clinical testing of rhLZ as an adjunct to commercial antibiotic
      treatment.

PMID- 21967197
TI  - Ubiquitination of heat shock protein 27 is mediated by its interaction with Smad
      ubiquitination regulatory factor 2 in A549 cells.
AB  - Smad ubiquitination regulatory factor 2 (Smurf2) is a crucial part of the
      ubiquitin-proteasome pathway (UPP) that regulates cellular signal transduction
      via ubiquitin-dependent degradation of some substrates and receptors. The
      biological function of Smurf2 in lung diseases, however, is not clear. In this
      study, the authors found that overexpression of Smurf2 altered the subcellular
      localization and distribution of heat shock protein 27 (HSP27), and induced a
      decrease of HSP27 protein levels through HSP27 degradation by the UPP in human
      lung adenocarcinoma epithelial cell line A549. Colocalized assay using confocal
      microscopy and coimmunoprecipitated reciprocally by either antibody indicated the
      interaction between Smurf2 and HSP27, which suggested that Smurf2 mediated
      ubiquitylation-dependent degradation of HSP27 through their interaction in A549
      cells.

PMID- 21967198
TI  - jTraML: an open source Java API for TraML, the PSI standard for sharing SRM
      transitions.
AB  - We here present jTraML, a Java API for the Proteomics Standards Initiative TraML
      data standard. The library provides fully functional classes for all elements
      specified in the TraML XSD document, as well as convenient methods to construct
      controlled vocabulary-based instances required to define SRM transitions. The use
      of jTraML is demonstrated via a two-way conversion tool between TraML documents
      and vendor specific files, facilitating the adoption process of this new
      community standard. The library is released as open source under the permissive
      Apache2 license and can be downloaded from  http://jtraml.googlecode.com . TraML
      files can also be converted online at  http://iomics.ugent.be/jtraml .

PMID- 21967199
TI  - Could fever and neuroinflammation play a role in the neurobiology of autism? A
      subject worthy of more research.
AB  - Autism is neuropsychiatric disorder in which a hyperglutamate state may play a
      role. It is suggested here that fever or hyperthermia may be able to alter
      glutamate levels in the brain and may therefore be able to impact on the symptoms
      of autism. More study on this possibility is clearly warranted.

PMID- 21967207
TI  - Positive psychology and war: an oxymoron.
AB  - The author was deeply disturbed by the January 2011 issue of the American
      Psychologist, which engendered a series of emotions in the author: first dismay,
      then anger, and finally a sense of shame about the current state of the
      profession. This was ostensibly an exposition of "positive psychology" principles
      and how they are to be applied in a colossal experiment designed to support our
      military in their fight against the ideology of jihadist Islam. The author found
      it hard to see what was positive in the presentation. Not one of the authors in
      this special issue discussed applying positive psychology principles to the
      reduction of conflict between nations, to the prevention of war, or to the
      promotion of peace. How about a positive psychology that questions the wisdom of
      leaders who tell us that the use of force is unavoidable, and seeks instead to
      help them find alternative, peaceful solutions? A true positive psychology should
      be primarily addressed to eradicating the disease of war, not to supporting those
      who fight it.

PMID- 21967208
TI  - Shock without awe.
AB  - In January 2011, the American Psychologist ran a special issue on "Comprehensive
      Soldier Fitness," edited by Martin Seligman and Michael Matthews. Thirteen
      articles described a collaborative effort by the U.S. Army and positive
      psychologists to "improve our force's resilience" (Casey, 2011, p. 1). If
      successful, one assumes, these efforts will make military engagements shorter
      (though not less frequent) and more victorious, while reducing human suffering on
      all sides. How can one object? Yet, the contributors themselves anticipated
      criticism. To justify their engagement with the military, they argued that
      psychological science has been relevant throughout its history, most notably
      during the world wars (Seligman & Fowler, 2011). They further noted that although
      the deployment of psychology may seem rushed, the exigency of the situation in
      the field demands it. Like other groups in conflict, the Army has an interest in
      standardizing the behavior of its members. To achieve this, the Army can threaten
      and deliver punishment. From the group's perspective, this interest is necessary
      and legitimate. It is, in the author's view, not legitimate for psychologists to
      obfuscate the conflict of interest between Army and soldier and to act as though
      they care, above all, about the well-being of the soldier.

PMID- 21967209
TI  - The dark side of comprehensive soldier fitness.
AB  - Comprehensive Soldier Fitness (CSF), the focus of the January 2011 special issue
      of the American Psychologist, is a $125 million resilience training initiative
      designed to reduce and prevent the adverse psychological consequences of combat
      for soldiers and veterans. These are worthy goals. Soldiers and veterans deserve
      the best care possible, and military psychologists have critically important
      roles to play. But the special issue is troubling in several important respects.
      Elsewhere, we have offered a detailed review (Eidelson, Pilisuk, & Soldz, 2011).
      Here we offer only a summary of our concerns. The CSF program is a massive
      research project launched without pilot testing to determine, first, the
      effectiveness of the training in a military environment. This is highly irregular
      and obviously worrisome considering the stakes. No evidence was provided
      indicating that CSF received preliminary review by an independent ethics review
      board. There are other ethically fraught possibilities.This special issue reveals
      much about current moral challenges facing the profession of psychology.

PMID- 21967210
TI  - Exposing the glosses in Seligman and Fowler's (2011) straw-man arguments.
AB  - The author was disappointed to see an entire special issue of the American
      Psychologist (January 2011) devoted to military psychology, but he was especially
      concerned about the one-sided moral justifications presented by Seligman and
      Fowler (2011) in the final article of the issue. The author feels they
      misrepresented potential objections to their program and dismissed the inherent
      dangers of cooperation between organized psychology and the military.

PMID- 21967211
TI  - Missing: critical and skeptical perspectives on comprehensive soldier fitness.
AB  - The author read with interest, and concern, the January 2011 issue of the
      American Psychologist. The Special Issue on Comprehensive Soldier Fitness
      addressed a hugely consequential national issue and offered a vision for
      psychological resilience along with an elaborate set of supporting articles,
      concluding with some comments on "Objections" to psychologists working with the
      military. While a bold vision was offered and a game plan presented, no data or
      evidence are yet available (it is far too early in the process), and that should
      concern us all. The author hopes the American Psychological Association (APA) and
      the American Psychologist offer skeptical and critical views in future issues on
      the issue of the psychological health of our military and as evidence emerges
      regarding the Comprehensive Soldier Fitness program.

PMID- 21967213
TI  - Ferromagnetic exchange couplings showing a chemical trend in Cu-Ln-Cu complexes
      (Ln = Gd, Tb, Dy, Ho, Er).
AB  - Exchange couplings in isomorphous [LnCu(2)] were evaluated by high-frequency
      electron paramagnetic resonance and magnetization studies. The exchange parameter
      J(Ln-Cu) was decreased with an increase in the atomic number; J(Ln-Cu)/k(B) =
      4.45(11), 2.27(6), 0.902(10), 0.334(3), and 0.136(8) K for Ln = Gd, Tb, Dy, Ho,
      and Er, respectively.

PMID- 21967214
TI  - Compound Astragalus and Salvia miltiorrhiza extract inhibits cell proliferation,
      invasion and collagen synthesis in keloid fibroblasts by mediating transforming
      growth factor-beta / Smad pathway.
AB  - BACKGROUND: The transforming growth factor (TGF)-beta/Smad pathway plays a key
      role in keloid development. We have previously demonstrated that compound
      Astragalus and Salvia miltiorrhiza extract (CASE) inhibits liver fibrosis and
      reduces invasion capacity of HepG2 cells by mediating the TGF-beta/Smad pathway.
      We therefore hypothesize that CASE may also exert antifibrotic effects in keloids
      by mediating the TGF-beta/Smad pathway. OBJECTIVES: To investigate the effects of
      CASE on cell proliferation, invasion and collagen synthesis in keloid
      fibroblasts, and to explore the effects of CASE on the TGF-beta/Smad signal
      pathway in order to elucidate its mechanisms of action. METHODS: The inhibitory
      effects of CASE on keloid fibroblasts were evaluated. Cell proliferation was
      studied by MTT assay; cell invasion was observed utilizing Transwell invasion
      chambers; and collagen synthesis in keloid fibroblasts was measured by (3) H
      proline incorporation assay. Expression of proteins induced by TGF-beta1 and
      their intracellular localization in keloid fibroblasts were investigated by
      Western blot and immunofluorescence, respectively. Plasminogen activator
      inhibitor-1 (PAI-1) transcriptional activity was measured by real-time reverse
      transcription-polymerase chain reaction. RESULTS: CASE significantly inhibited
      cell proliferation induced by newborn bovine serum as well as collagen synthesis
      and cell invasion induced by TGF-beta1 in keloid fibroblasts, while it showed
      weak effects on normal fibroblasts. The phosphorylation of Smad2/3 was markedly
      reduced by CASE treatment, while CASE exhibited stronger inhibitory effects on
      linker region phosphorylation (pSmad2L and pSmad3L) compared with effects on C
      terminal region phosphorylation (pSmad2C and pSmad3C). In addition, CASE blocked
      formation of Smad2/3/4 complexes and their nuclear translocation, but upregulated
      Smad7 expression in a dose-dependent manner. PAI-1 mRNA and protein levels were
      also suppressed by CASE treatment. CONCLUSIONS: These results suggest that CASE
      exhibits inhibitory effects on cell proliferation, invasion and collagen
      synthesis in keloid fibroblasts, and its mechanisms of action may involve the TGF
      beta/Smad pathway.

PMID- 21967215
TI  - Residue analysis and degradation studies of fenbuconazole and myclobutanil in
      strawberry by chiral high-performance liquid chromatography-tandem mass
      spectrometry.
AB  - A simple and sensitive enantioselective method for the determination of
      fenbuconazole and myclobutanil in strawberry was developed by high-performance
      liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Fenbuconazole and
      myclobutanil residues in strawberry were extracted with acetonitrile containing
      1% acetic acid, and an aliquot was cleaned up with PSA (primary and secondary
      amine) and C(18) sorbent. The direct resolution of fenbuconazole and myclobutanil
      enantiomers was performed on a cellulose tris (3,5-dimethylphenylcarbamate)
      column using acetonitrile-0.1% formic acid solution (60:40, v/v) as the mobile
      phase. Quantification was achieved using matrix-matched standard calibration
      curves, and the limits of quantification for fenbuconazole and myclobutanil
      enantiomers in strawberry were both 2 MUg/kg. The method was successfully
      utilized to investigate the probable enantioselective degradation of
      fenbuconazole and myclobutanil in strawberry. The results showed that the
      degradation of the fenbuconazole and myclobutanil enantiomers in strawberry
      followed pseudofirst-order kinetics (R(2) > 0.97). The results from this study
      revealed that the degradation of fenbuconazole in strawberry was not
      enantioselective, while the degradation of myclobutanil was enantioselective, and
      the (+)-myclobutanil showed a faster degradation than (-)-myclobutanil in
      strawberry, resulting in the relative enrichment of (-)-myclobutanil in residue.
      The results could provide a reference to fully evaluate the risks of these two
      fungicides.

PMID- 21967216
TI  - Possible roles of ENaC and Cl(-) channel in wound closure in Xenopus laevis
      embryos.
AB  - Our previous report showed that rapid wound closure in Xenopus laevis embryos was
      associated with a decrease in the extracellular concentration of either Na(+) or
      Cl(-) ions. In this study, we examined the wound closure in Xenopus embryos when
      epithelial Na(+) channel (ENaC), Na(+)/K(+) ATPase (Na(+) pump) or CICs (members
      of Cl(-) channel) were blocked by each specific inhibitor. Blockage of ENaC and
      CIC restricted the rate of wound closure during the first 30 min PW and during
      the subsequent period, respectively. In contrast, inhibition of Na(+) pump had no
      effect on the rate of wound closure. Furthermore, simultaneous administration of
      both ENaC and CIC inhibitors resulted in the cumulative reduction of wound
      closure. Thus, it is plausible that these ion channels play active roles in wound
      closure in Xenopus embryos. NPPB is known to inhibit both CIC-2 and CIC-3.
      Immunohistochemical experiments showed that CIC-3, but not CIC-2, was expressed
      in Xenopus embryos, suggesting that the reduced wound closure by NPPB was due to
      blockage of CIC-3. A local enhancement of CIC-3 expression at the leading edge of
      the wounded epidermis was found to be specific to closing wounds that were kept
      in 10% NAM. An in vitro wounding assay also showed a pattern of CIC-3 expression
      at the margin of the scratch wound comparable to the results in vivo. These
      findings suggest that intracellular translocation of CIC-3 is involved in wound
      closure. We propose that the ion channels, including CIC-3, play a crucial role
      in wound closure in Xenopus embryos.

PMID- 21967217
TI  - Geographical distributions of mitochondrial DNA lineages reflect ancient
      directions of river flow: a case study of the Japanese freshwater shrimp
      Neocaridina denticulata denticulata (Decapoda: Atyidae).
AB  - The mitochondrial DNA phylogeographical structure of the freshwater atyid shrimp
      Neocaridina denticulata denticulata was investigated near the Yura and Kako
      Rivers in western Japan. To assess the biological significance of drainage
      evolution, fragments of 390 base pairs (bp) extending from the NADH dehydrogenase
      subunit 2 gene to the tryptophan transfer RNA gene were sequenced for 246
      specimens from twenty locations. The phylogenetic tree detected two distinct
      clades corresponding to the region along the Sea of Japan and Seto Inland Sea,
      respectively. Geographical mapping of the two clades well reflected the river
      capture, in which the upper reaches of the Yura River draining into the Sea of
      Japan had been captured from the Kako River into the Seto Inland Sea. The clear
      pattern of mitochondrial DNA distribution may be accounted for by the ecological
      characteristics of species that minimize passive downstream drift, local
      adaptation, and mountain topography.

PMID- 21967218
TI  - Relative antidipsogenic potencies of six homologous natriuretic peptides in eels.
AB  - Atrial natriuretic peptide (ANP) exhibits a potent antidipsogenic effect in
      seawater (SW) eels to limit excess Na(+) uptake, thereby effectively promoting SW
      adaptation. Recently, cardiac ANP, BNP and VNP and brain CNP1, 3 and 4, have been
      identified in eels. We examined the antidipsogenic effect of all homologous NPs
      using conscious, cannulated eels in both FW and SW together with parameters that
      affect drinking. A dose-response study (0.01-1 nmol/kg) in SW eels showed the
      relative potency of the antidipsogenic effect was in the order ANP >= VNP > BNP =
      CNP3 > CNP1 >= CNP4, while the order was ANP = VNP = BNP > CNP3 = CNP1 = CNP4 for
      the vasodepressor effect. The minimum effective dose of ANP for the
      antidipsogenic effect is much lower than that in mammals. ANP, BNP and VNP at 0.3
      nmol/kg decreased drinking, plasma Na(+) concentration and aortic pressure and
      increased hematocrit in SW eels. The cardiac NPs induced similar changes in
      drinking, aortic pressure and hematocrit in FW eels, but aside from BNP no change
      in plasma Na(+) concentration. CNPs had no effect on drinking, plasma Na(+)
      concentration and hematocrit but induced mild hypotension in both FW and SW eels,
      except for CNP3 that inhibited drinking in SW eels. These results show that ANP,
      BNP and VNP are potent antidipsogenic hormones in eels in spite of other
      regulatory factors working to induce drinking, and that CNPs are without effects
      on drinking except for the ancestor of the cardiac NPs, CNP3.

PMID- 21967219
TI  - Immunolocalization of androgen receptor, aromatase cytochrome P450, estrogen
      receptor alpha and estrogen receptor beta proteins during the breeding season in
      scent glands of muskrats (Ondatra zibethicus).
AB  - Aromatase cytochrome P450 (P450arom) is an enzyme that catalyzes the conversion
      of androgen to estrogen. Expression of P450arom in extra-gonadal sites and
      locally-synthesized estrogen play an important role in physiological conditions.
      The purpose of this study was to investigate the cellular immunolocalization of
      androgen receptor (AR), P450arom, estrogen receptor alpha (ERa) and estrogen
      receptor beta (ERbeta) in muskrat scent glands during the breeding season.
      Histological observation and immunohistochemistry of AR, P450arom, ERa and ERbeta
      were performed in the muskrat scent glands. In addition, total proteins were
      extracted from scent glandular tissues in the breeding season and were used for
      Western blotting analysis for AR, P450arom, ERalpha and ERbeta. Histologically,
      glandular cells, interstitial cells, epithelial cells of the excretory duct and
      the excretory tubules were identified in the muskrat scent glands during the
      breeding season. AR was only observed in glandular cells of scent glands;
      P450arom was expressed in glandular cells and epithelial cells of the excretory
      duct; ERalpha was found in glandular cells, interstitial cells and epithelial
      cells of the excretory duct, whereas ERbeta was present in glandular cells and
      epithelial cells of the excretory duct. Also, the positive signals of AR,
      P450arom, ERalpha and ERbeta by Western blotting were all observed in scent
      glandular tissues. These results suggested that the scent gland is the target
      organ of androgens and estrogens, and that estrogens may play an important
      autocrine or paracrine role in glandular function of the muskrats.

PMID- 21967220
TI  - Sexual dimorphism of gonadotropin-releasing hormone type-III (GnRH3) neurons and
      hormonal sex reversal of male reproductive behavior in Mozambique tilapia.
AB  - In tilapia, hormone treatment during the period of sexual differentiation can
      alter the phenotype of the gonads, indicating that endocrine factors can cause
      gonadal sex reversal. However, the endocrine mechanism underlying sex reversal of
      reproductive behaviors remains unsolved. In the present study, we detected sexual
      dimorphism of gonadotropin-releasing hormone type III (GnRH3) neurons in
      Mozambique tilapia Oreochromis mossambicus. Our immunohistochemical observations
      showed sex differences in the number of GnRH3 immunoreactive neurons in mature
      tilapia; males had a greater number of GnRH3 neurons in the terminal ganglion
      than females. Treatment with androgen (11-ketotestosterone (11-KT) or
      methyltestosterone), but not that with 17beta-estradiol, increased the number of
      GnRH3 neurons in females to a level similar to that in males. Furthermore, male
      specific nest-building behavior was induced in 70% of females treated with 11-KT
      within two weeks after the onset of the treatment. These results indicate
      androgen-dependent regulation of GnRH3 neurons and nest-building behavior,
      suggesting that GnRH3 is importantly involved in sex reversal of male-specific
      reproductive behavior.

PMID- 21967221
TI  - DNA sexing of Nipponia nippon by duplex polymerase chain reaction.
AB  - The aim of this study was to develop a rapid, simple, sensitive, and accurate
      duplex polymerase chain reaction (PCR) to sex Nipponia nippon, a monomorphic
      bird. Amplification by duplex PCR of a sex-related gene on the female chromosome
      and the 12S rRNA gene yielded good results using genomic DNA extracted from a
      feather follicle or the membranes of eggshell samples. To simplify the DNA
      extraction procedure, a simple boiling method was used. Our simple boiling DNA
      extraction method produced similar PCR amplification results as when using DNA
      extracted using TRIzol. Sex determination in the endangered Nipponia nippon is of
      crucial value to breeding programs. The duplex PCR protocol that we developed
      provides a simple sex identification method that is based on amplification of a
      sex-related gene, and we anticipate that it will facilitate effective
      conservation and management of Nipponia nippon.

PMID- 21967222
TI  - Comparative morphology of the skin of Natrix tessellata (family: Colubridae) and
      Cerastes vipera (family: Viperidae).
AB  - We studied beneficial difference of the skin of two snakes. Two snakes were
      chosen from two different habitats and two families: Colubridae (Natrix
      tessellata) and Viperidae (Cerastes vipera). The investigations were performed by
      light and electron microscopy. Histologically, the skin of the studied species
      show pronounced modifications that correlated with functional demands. The scales
      in Natrix tessellata overlapped slightly, while in Cerastes vipera they were
      highly overlapped. SEM shows that scales of Natrix tessellata had bidentate tips
      while the scales of Cerastes vipera were keeled. Histochemically, in both studied
      species, melanocytes and collagenous fibres were distributed throughout the
      dermis. Polysaccharides were highly concentrated in the epidermis and dermis of
      both species while proteins were highly concentrated only in the epidermis.
      Transmission electron microscopy (TEM) showed that the skin of both snakes
      consisted of keratins located in the epidermis. Some lipids and mucus were
      incorporated into the outer scale surfaces such that lipids were part of the
      fully keratinised hard layer of the snakes' skins. Lipids are probably
      responsible for limiting water loss and ion movements across the skin.
      Melanosomes from epidermal melanocytes were present only in Cerastes vipera. In
      aggregate, these results indicate that snakeskin may provide an ecological
      indicator whereby epidermal and integumentary specializations may be ecologically
      correlated.

PMID- 21967223
TI  - Molecular systematics of Tanaidacea (Crustacea: Peracarida) based on 18S sequence
      data, with an amendment of suborder/superfamily-level classification.
AB  - Phylogenetic relationships within Tanaidacea were analyzed based on sequence data
      for the 18S rRNA gene. Our results strongly supported a monophyletic group
      composed of Neotanaidae, Tanaoidea, and Paratanaoidea, with the first two taxa
      forming a clade. These results contradict three previously suggested hypotheses
      of relationships. Based on the molecular results, and considering morphological
      similarities/differences between Neotanaidomorpha and Tanaidomorpha, we demoted
      Suborder Neotanaidomorpha to Superfamily Neotanaoidea within Tanaidomorpha; with
      this change, the classification of extant tanaidaceans becomes a two-suborder,
      four-superfamily system. This revision required revision of the diagnoses for
      Tanaidomorpha and its three super-families. The results for Apseudomorpha were
      ambiguous: this taxon was monophyletic in the maximum likelihood and Bayesian
      analyses, but paraphyletic in the maximum parsimony and minimum evolution
      analyses.

PMID- 21967224
TI  - Evidence for true fall-mating in Japanese newt Cynops pyrrhogaster.
AB  - The mating season of Japanese newt Cynops pyrrhogaster is generally thought to
      occur once a year in spring to early summer, during the months of April to June,
      as in many other Japanese amphibians. However, in fall, from September to
      October, we often observed breeding colored males demonstrating a mating behavior
      with females in the field. In this study, in order to identify their true mating
      season, we anatomically and histologically investigated the annual maturation
      cycle of gonads and reproductive organs, including cloacal spermathecae in
      females, and, using a molecular marker, identified the seasonal origins of sperm,
      which are released in spring to perform insemination. We found that, in fall,
      ovaries are somewhat immature, while the testes were mature and the sperm already
      stored in the deferent ducts. Females stored a significant amount of sperm in
      around 80% of the spermatechae examined in October and 100% in December. When
      artificially ovulated in March before contact with male partners after
      hibernation, the females spawned fertilized eggs and these developed normally.
      Finally, we identified heterozygous genotypes of the visual pigment gene for the
      two different population types in the embryos, which were derived from a female
      who established contact with males of the same population in fall and then
      switched to males from another population until oviposition in spring. We
      therefore, conclude that the true mating season of this species occurs from fall
      to early summer, interrupted only by winter, and lasts six months longer (from
      October to June) than generally believed.

PMID- 21967225
TI  - Interaction of relaxin-like gonad-stimulating substance with ovarian follicle
      cells of the starfish Asterina pectinifera.
AB  - Previously, gonad-stimulating substance (GSS), which acts as a gonadotropin, was
      purified from radial nerves of the starfish Asterina pectinifera and its
      structure was elucidated. Here, the interaction of GSS with receptors was
      examined in ovarian follicle cells, a target of GSS. In competitive experiments
      using radioiodinated and radioinert GSS, highly specific binding was observed in
      the microsomal/plasma membrane fraction of follicle cells. GSS scarcely bound in
      the cytosolic fraction. Scatchard plots showed the numbers of binding sites (NBS)
      in whole homogenate and the crude membrane to be 1.65 and 3.42 pmoles/mg protein,
      respectively. Dissociation constant (K (d)) values in these two preparations were
      almost the same at about 0.6-0.7 nM. Furthermore, it was shown that GSS
      stimulated adenylyl cyclase activity in follicle cell membranes in a dose
      dependent manner that required GTP. Immunoblotting with specific antibodies for G
      protein subunits after SDS-PAGE of the membrane preparation showed both
      stimulatory (Gs) and inhibitory (Gi) regulatory alpha-subunits for adenylyl
      cyclase and a beta-subunit. The results strongly suggest that GSS interacts with
      G-protein-coupled receptors (GPCR) located in the follicle cell membrane to
      stimulate Gs-protein and adenylyl cyclase activity.

PMID- 21967228
TI  - Compound heterozygous mutations p.Q1530X and 6103delG in COL7A1 causing recessive
      dystrophic epidermolysis bullosa in a Pakistani family.

PMID- 21967229
TI  - Uncertain sightings and the extinction of the Ivory-billed Woodpecker.
AB  - The extinction of a species can be inferred from a record of its sightings.
      Existing methods for doing so assume that all sightings in the record are valid.
      Often, however, there are sightings of uncertain validity. To date, uncertain
      sightings have been treated in an ad hoc way, either excluding them from the
      record or including them as if they were certain. We developed a Bayesian method
      that formally accounts for such uncertain sightings. The method assumes that
      valid and invalid sightings follow independent Poisson processes and use
      noninformative prior distributions for the rate of valid sightings and for a
      measure of the quality of uncertain sightings. We applied the method to a
      recently published record of sightings of the Ivory-billed Woodpecker
      (Campephilus principalis). This record covers the period 1897-2010 and contains
      39 sightings classified as certain and 29 classified as uncertain. The Bayes
      factor in favor of extinction was 4.03, which constitutes substantial support for
      extinction. The posterior distribution of the time of extinction has 3 main modes
      in 1944, 1952, and 1988. The method can be applied to sighting records of other
      purportedly extinct species.

PMID- 21967227
TI  - Glycation-altered proteolysis as a pathobiologic mechanism that links dietary
      glycemic index, aging, and age-related disease (in nondiabetics).
AB  - Epidemiologic studies indicate that the risks for major age-related debilities
      including coronary heart disease, diabetes, and age-related macular degeneration
      (AMD) are diminished in people who consume lower glycemic index (GI) diets, but
      lack of a unifying physiobiochemical mechanism that explains the salutary effect
      is a barrier to implementing dietary practices that capture the benefits of
      consuming lower GI diets. We established a simple murine model of age-related
      retinal lesions that precede AMD (hereafter called AMD-like lesions). We found
      that consuming a higher GI diet promotes these AMD-like lesions. However, mice
      that consumed the lower vs. higher GI diet had significantly reduced frequency (P
      < 0.02) and severity (P < 0.05) of hallmark age-related retinal lesions such as
      basal deposits. Consuming higher GI diets was associated with > 3 fold higher
      accumulation of advanced glycation end products (AGEs) in retina, lens, liver,
      and brain in the age-matched mice, suggesting that higher GI diets induce
      systemic glycative stress that is etiologic for lesions. Data from live cell and
      cell-free systems show that the ubiquitin-proteasome system (UPS) and
      lysosome/autophagy pathway [lysosomal proteolytic system (LPS)] are involved in
      the degradation of AGEs. Glycatively modified substrates were degraded
      significantly slower than unmodified substrates by the UPS. Compounding the
      detriments of glycative stress, AGE modification of ubiquitin and ubiquitin
      conjugating enzymes impaired UPS activities. Furthermore, ubiquitin conjugates
      and AGEs accumulate and are found in lysosomes when cells are glycatively
      stressed or the UPS or LPS/autophagy are inhibited, indicating that the UPS and
      LPS interact with one another to degrade AGEs. Together, these data explain why
      AGEs accumulate as glycative stress increases.

PMID- 21967231
TI  - Recognition confidence under violated and confirmed memory expectations.
AB  - Individuals' memory experiences typically covary with those of others' around
      them, and on average, an item is more likely to be familiar if a companion
      recommends it as such. Although it would be ideal if observers could use the
      external recommendations of others' as statistical priors during recognition
      decisions, it is currently unclear how or if they do so. Furthermore,
      understanding the sensitivity of recognition judgments to such external cues is
      critical for understanding memory conformity and eyewitness suggestibility
      phenomena. To address this we examined recognition accuracy and confidence
      following cues from an external source (e.g., "Likely Old") that forecast the
      likely status of upcoming memory probes. Three regularities emerged. First, hit
      and correct-rejection rates expectedly fell when participants were invalidly
      versus validly cued. Second, hit confidence was generally higher than correct
      rejection confidence, regardless of cue validity. Finally, and most noteworthy,
      cue validity interacted with judgment confidence such that validity heavily
      influenced the confidence of correct rejections but had no discernible influence
      on the confidence of hits. Bootstrap-informed Monte Carlo simulation supported a
      dual process recognition model under which familiarity and recollection processes
      counteract to heavily dampen the influence of external cues on average reported
      confidence. A 3rd experiment tested this model using source memory. As predicted,
      because source memory is heavily governed by contextual recollection, cue
      validity again did not affect confidence, although as with recognition it clearly
      altered accuracy.

PMID- 21967230
TI  - Calcium signals in the nucleus accumbens: activation of astrocytes by ATP and
      succinate.
AB  - BACKGROUND: Accumulating evidence suggests that glial signalling is activated by
      different brain functions. However, knowledge regarding molecular mechanisms of
      activation or their relation to neuronal activity is limited. The purpose of the
      present study is to identify the characteristics of ATP-evoked glial signalling
      in the brain reward area, the nucleus accumbens (NAc), and thereby to explore the
      action of citric acid cycle intermediate succinate (SUC). RESULTS: We described
      the burst-like propagation of Ca2+ transients evoked by ATP in acute NAc slices
      from rat brain. Co-localization of the ATP-evoked Ca2+ signalling with
      immunoreactivities of the astroglia-specific gap junction forming channel protein
      connexin43 (Cx43) and the glial fibrillary acidic protein (GFAP) indicated that
      the responsive cells were a subpopulation of Cx43 and GFAP immunoreactive
      astrocytes. The ATP-evoked Ca2+ transients were present under the blockade of
      neuronal activity, but were inhibited by Ca2+ store depletion and antagonism of
      the G protein coupled purinergic P2Y1 receptor subtype-specific antagonist
      MRS2179. Similarly, Ca2+ transients evoked by the P2Y1 receptor subtype-specific
      agonist 2-(Methylthio)adenosine 5'-diphosphate were also blocked by MRS2179.
      These characteristics implied that intercellular Ca2+ signalling originated from
      the release of Ca2+ from internal stores, triggered by the activation of P2Y1
      receptors. Inhibition by the gap junction blockers carbenoxolone and flufenamic
      acid and by an antibody raised against the gating-associated segment of Cx43
      suggested that intercellular Ca2+ signalling proceeded through gap junctions. We
      demonstrated for the first time that extracellular SUC also evoked Ca2+
      transients (EC50 = 50-60 MUM) in about 15% of the ATP-responsive NAc astrocytes.
      By contrast to glial cells, electrophysiologically identified NAc neurons
      surrounded by ATP-responsive astrocytes were not activated simultaneously.
      CONCLUSIONS: We concluded, therefore, that ATP- and SUC-sensitive Ca2+ transients
      appear to represent a signalling layer independent of NAc neurons. This
      previously unrecognised glial action of SUC, a major cellular energy metabolite,
      may play a role in linking metabolism to Ca2+ signalling in astrocytic networks
      under physiological and pathological conditions such as exercise and metabolic
      diseases.

PMID- 21967232
TI  - Antinociceptive activity of a synthetic curcuminoid analogue, 2,6-bis-(4-hydroxy
      3-methoxybenzylidene)cyclohexanone, on nociception-induced models in mice.
AB  - This study investigated the potential antinociceptive efficacy of a novel
      synthetic curcuminoid analogue, 2,6-bis-(4-hydroxy-3
      methoxybenzylidene)cyclohexanone (BHMC), using chemical- and thermal-induced
      nociception test models in mice. BHMC (0.03, 0.1, 0.3 and 1.0 mg/kg) administered
      via intraperitoneal route (i.p.) produced significant dose-related inhibition in
      the acetic acid-induced abdominal constriction test in mice with an ID(50)  of
      0.15 (0.13-0.18) mg/kg. It was also demonstrated that BHMC produced significant
      inhibition in both neurogenic (first phase) and inflammatory phases (second
      phase) of the formalin-induced paw licking test with an ID(50)  of 0.35 (0.27
      0.46) mg/kg and 0.07 (0.06-0.08) mg/kg, respectively. Similarly, BHMC also
      exerted significant increase in the response latency period in the hot-plate
      test. Moreover, the antinociceptive effect of the BHMC in the formalin-induced
      paw licking test and the hot-plate test was antagonized by pre-treatment with the
      non-selective opioid receptor antagonist, naloxone. Together, these results
      indicate that the compound acts both centrally and peripherally. In addition,
      administration of BHMC exhibited significant inhibition of the neurogenic
      nociception induced by intraplantar injections of glutamate and capsaicin with
      ID(50)  of 0.66 (0.41-1.07) mg/kg and 0.42 (0.38-0.51) mg/kg, respectively.
      Finally, it was also shown that BHMC-induced antinociception was devoid of toxic
      effects and its antinociceptive effect was associated with neither muscle
      relaxant nor sedative action. In conclusion, BHMC at all doses investigated did
      not cause any toxic and sedative effects and produced pronounced central and
      peripheral antinociceptive activities. The central antinociceptive activity of
      BHMC was possibly mediated through activation of the opioid system as well as
      inhibition of the glutamatergic system and TRPV1 receptors, while the peripheral
      antinociceptive activity was perhaps mediated through inhibition of various
      inflammatory mediators.

PMID- 21967234
TI  - F-LARSP 1.0: an adaptation of the LARSP language profile for French.
AB  - The Language Assessment, Remediation and Screening Procedure (Crystal, Fletcher
      and Garman, 1976; The grammatical analysis of language disability. London: Edward
      Arnold) is a linguistic profile commonly used by researchers and clinicians to
      carry out detailed analyses of the grammar and morphology of children's
      spontaneous language samples. This article discusses the methods used to adapt
      the profile from English to French using a large corpus of child language in
      order to accurately assign morphosyntactic structures to age-based stages.

PMID- 21967233
TI  - Remote exosites of the catalytic domain of matrix metalloproteinase-12 enhance
      elastin degradation.
AB  - How does matrix metalloproteinase-12 (MMP-12 or metalloelastase) degrade elastin
      with high specific activity? Nuclear magnetic resonance suggested soluble elastin
      covers surfaces of MMP-12 far from its active site. Two of these surfaces have
      been found, by mutagenesis guided by the BINDSIght approach, to affect
      degradation and affinity for elastin substrates but not a small peptide
      substrate. Main exosite 1 has been extended to Asp124 that binds calcium. Novel
      exosite 2 comprises residues from the II-III loop and beta-strand I near the back
      of the catalytic domain. The high degree of exposure of these distal exosites may
      make them accessible to elastin made more flexible by partial hydrolysis.
      Importantly, the combination of one lesion each at exosites 1 and 2 and the
      active site decreased the catalytic competence toward soluble elastin by 13-18
      fold to the level of MMP-3, homologue and poor elastase. Double-mutant cycle
      analysis of conservative mutations of Met156 (exosite 2) and either Asp124
      (exosite 1) or Ile180 (active site) showed they had additive effects. Compared to
      polar substitutions observed in other MMPs, Met156 enhanced affinity and Ile180
      the k(cat) for soluble elastin. Both residues detracted from the higher folding
      stability with polar mutations. This resembles the trend in enzymes of an inverse
      relationship between folding stability and activity. Restoring Asp124 from
      combination mutants enhanced the k(cat) for soluble elastin. In elastin
      degradation, exosites 1 and 2 contributed in a manner independent of each other
      and Ile180 at the active site, but with partial coupling to Ala182 near the
      active site. The concept of weak, separated interactions coalescing somewhat
      independently can be extended to this proteolytic digestion of a protein from
      fibrils.

PMID- 21967236
TI  - Mechanical restraint--which interventions prevent episodes of mechanical
      restraint?- a systematic review.
AB  - PURPOSE: To identify interventions preventing mechanical restraints. DESIGN AND
      METHODS: Systematic review of international research papers dealing with
      mechanical restraint. The review combines qualitative and quantitative research
      in a new way, describing the quality of evidence and the effect of intervention.
      FINDINGS: Implementation of cognitive milieu therapy, combined interventions, and
      patient-centered care were the three interventions most likely to reduce the
      number of mechanical restraints. PRACTICE IMPLICATIONS: There is a lack of high
      quality and effective intervention studies. This leaves patients and metal health
      professionals with uncertainty when choosing interventions in an attempt to
      prevent mechanical restraints.

PMID- 21967235
TI  - The prevalence of neuromyelitis optica in South East Wales.
AB  - BACKGROUND AND PURPOSE: Neuromyeltis optica (NMO) is a neuroinflammatory disorder
      considered rare in Caucasian populations. However, accurate population-based
      epidemiological data for NMO and NMO spectrum disorder (NMO-SD) from Western
      populations employing validated diagnostic criteria remain limited. We sought
      therefore to estimate the prevalence and clinical features of NMO in a north
      European Caucasian population in South East Wales. METHODS: Patients were
      identified by a comprehensive, multistage ascertainment strategy employing a
      regional neuroinflammatory disease register, hospital diagnostic databases
      personal physician referrals and regional requests for anti-aquaporin-4
      antibodies (anti-AQP4). RESULTS: Fourteen Caucasian patients (11 patients with
      NMO and three with NMO-SD) were identified in a population of 712,572
      (19.6/million; 95% CIs: 12.2-29.7). There was an excess of females (female:male
      12:2), 11/14 were anti-AQP4 positive and 5/14 had disease onset under the age of
      20 years. CONCLUSION: This study suggests that NMO and related spectrum disorders
      are at least as frequent in Northern European populations as in non-Caucasian
      populations and that the demographic profile of prevalent patients differs from
      clinic-based cohorts.

PMID- 21967240
TI  - Mycobiota and mycotoxins in malted barley and brewer's spent grain from
      Argentinean breweries.
AB  - AIMS: To evaluate mycobiota and aflatoxins B(1) (AFB(1)), B(2) (AFB(2)), G(1)
      (AFG(1)), G(2) (AFG(2)) and fumonisin B(1) (FB(1)) contamination in different
      malted barley types and brands and brewer's grain collected from a major
      Argentinean brewery. METHODS AND RESULTS: Total fungal counts were performed
      using the plate count method. Aflatoxin B(1), AFB(2), AFG(1), AFG(2) and
      Zearalenone (ZEA) analyses were performed by thin-layer chromatography (TLC).
      Fumonisin B(1) was determined by HPLC. Eighty-three percentage of the malted
      barley (100% M1, 50% M2 and 100% M3) and 61% of brewer's grain samples had a
      count >1 * 10(4) CFU g(-1). Yeasts were isolated from all malt and brewer's grain
      samples. Genera containing some of the most important mycotoxin producer species-
      Fusarium ssp., Aspergillus ssp., Penicillium ssp. and Alternaria ssp.--were
      isolated from the analysed samples, along with other environmental saprophytic
      fungi such as Geotrichum ssp., Mucorales and Cladosporium ssp. All samples were
      contaminated with 104-145 MUg kg(-1) FB(1). Eighteen per cent of brewer's grain
      samples were contaminated with 19-44.52 MUg kg(-1) AFB(1). Aflatoxin B(2),
      AFG(1), AFG(2) and ZEA were not detected in any of the analysed samples.
      CONCLUSIONS: Fungal and mycotoxin contamination in malt and brewer's grain is an
      actual risk for animal and human health. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This study may be useful for assessing the risk of mycotoxins in Argentinean
      beers and especially in animal feeds.

PMID- 21967241
TI  - Factors influencing adherence to antiretroviral treatment in Asian developing
      countries: a systematic review.
AB  - OBJECTIVE: To systematically review the literature of factors affecting adherence
      to Antiretroviral treatment (ART) in Asian developing countries. METHODS:
      Database searches in Medline/Ovid, Cochrane library, CINAHL, Scopus and PsychINFO
      for studies published between 1996 and December 2010. The reference lists of
      included papers were also checked, with citation searching on key papers.
      RESULTS: A total of 437 studies were identified, and 18 articles met the
      inclusion criteria and were extracted and critically appraised, representing in
      12 quantitative, four qualitative and two mixed-method studies. Twenty-two
      individual themes, including financial difficulties, side effects, access, stigma
      and discrimination, simply forgetting and being too busy, impeded adherence to
      ART, and 11 themes, including family support, self-efficacy and desire to live
      longer, facilitated adherence. CONCLUSION: Adherence to ART varies between
      individuals and over time. We need to redress impeding factors while promoting
      factors that reinforce adherence through financial support, better accessible
      points for medicine refills, consulting doctors for help with side effects,
      social support and trusting relationships with care providers.

PMID- 21967242
TI  - Vascular endothelial dysfunction in patients with newly diagnosed type 2 diabetes
      and effects of 2-year and 5-year multifactorial intervention.
AB  - OBJECTIVES: Investigate short- and long-term effect of multifactorial
      intervention on endothelial dysfunction in patients with newly diagnosed type 2
      diabetes. BACKGROUND: Whether multifactorial intervention reduces cardiovascular
      risk in type 2 diabetes is largely controversial, partially because of lack of
      reliable method for endothelial dysfunction detection. Using high-resolution
      ultrasonographical flow-mediated vasodilatation (FMD), we completed a 5-year
      randomized prospective intervention trial in patients with newly diagnosed type 2
      diabetes. We have studied the effect of multifactorial intervention therapy on
      their endothelial dysfunction. METHODS: One hundred eight patients with newly
      diagnosed type 2 diabetes, and 83 healthy subjects received measurement of
      brachial artery FMD and endothelium-independent dilatation (EID). Diabetic
      patients were assigned into four groups, treated with: (A) hypoglycemic and
      antihypertensive agents, (B) hypoglycemic, antihypertensive and lipid-lowering
      agents, (C) hypoglycemic, antihypertensive and lipid-lowering agents, and vitamin
      E, and (D) hypoglycemic, antihypertensive and lipid-lowering agents, and compound
      salvia tablets. Both FMD and EID were remeasured after 24- and 60-month
      treatment. RESULTS: FMD in diabetic patients was significantly lower than those
      in healthy subjects. After 24-month treatment, there was no FMD change. However,
      FMD improved significantly after 60-month treatment. The differences between 24-
      and 60-month are also significant. EID did not change significantly after both 24
      and 60-month treatments. CONCLUSIONS: (1) FMD-detectable endothelial dysfunction
      exists in newly diagnosed type 2 diabetic patients. (2) Reverse of endothelial
      function occurs only after long-term (60-month) multifactorial intervention. (3)
      FMD could potentially help early identification, stratification, and treatment of
      endothelial dysfunction in type 2 diabetic patients.

PMID- 21967243
TI  - Improvement in scalp hair growth in androgen-deficient women treated with
      testosterone: a questionnaire study.
AB  - BACKGROUND: Androgens are thought to have an adverse effect on female scalp hair
      growth. However, our clinical experience of androgen replacement therapy in women
      with androgen deficiency, in which hair loss was seldom reported, led us to
      question this concept. OBJECTIVES: To evaluate the effect of subcutaneous
      testosterone therapy on scalp hair growth in female patients. METHODS: A total of
      285 women, treated for a minimum of 1year with subcutaneous testosterone implants
      for symptoms of androgen deficiency, were asked to complete a survey that
      included questions on scalp and facial hair. Age, body mass index (BMI) and serum
      testosterone levels were examined. RESULTS: Out of the 285 patients, 76 (27%)
      reported hair thinning prior to treatment; 48 of these patients (63%) reported
      hair regrowth on testosterone therapy (responders). Nonresponders (i.e. no
      reported hair regrowth on therapy) had significantly higher BMIs than responders
      (P=0.05). Baseline serum testosterone levels were significantly lower in women
      reporting hair loss prior to therapy than in those who did not (P=0.0001). There
      was no significant difference in serum testosterone levels, measured 4weeks after
      testosterone implantation, between responders and nonresponders. No patient in
      this cohort reported scalp hair loss on testosterone therapy. A total of 262
      women (92%) reported some increase in facial hair growth. CONCLUSIONS:
      Subcutaneous testosterone therapy was found to have a beneficial effect on scalp
      hair growth in female patients treated for symptoms of androgen deficiency. We
      propose this is due to an anabolic effect of testosterone on hair growth. The
      fact that no subject complained of hair loss as a result of treatment casts doubt
      on the presumed role of testosterone in driving female scalp hair loss. These
      results need to be confirmed by formal measurements of hair growth.

PMID- 21967244
TI  - Reactive oxygen species driven angiogenesis by inorganic nanorods.
AB  - The exact mechanism of angiogenesis by europium hydroxide nanorods was unclear.
      In this study we have showed that formation of reactive oxygen species (H(2)O(2)
      and O(2).-) is involved in redox signaling pathways during angiogenesis,
      important for cardiovascular and ischemic diseases. Here we used single-walled
      carbon nanotube sensor array to measure the single-molecule efflux of H(2)O(2)
      and a HPLC method for the determination of O(2).- from endothelial cells in
      response to proangiogenic factors. Additionally, reactive oxygen species-mediated
      angiogenesis using inorganic nanorods was observed in transgenic (fli1a:EGFP)
      zebrafish embryos.

PMID- 21967245
TI  - Use of fecundity measured directly throughout the breeding season to test a
      source-sink demographic model.
AB  - Populations of landbirds (bird species that occupy terrestrial habitats for most
      of their life cycle) are declining throughout North America (north of Mexico) and
      Europe, yet little is known about how demography is driving this trend. A recent
      model of 5 geographically separated populations of Cerulean Warblers (Dendroica
      cerulea) that was based on within-season sampling of nest survival and fledgling
      success shows that all populations are sinks (annual reproduction is consistently
      less than annual adult mortality). I tested this indirect model by directly
      measuring fecundity (number of female fledglings/female) during the breeding
      season for 2 years in a Cerulean Warbler population occupying a mature forest in
      southwestern Michigan (U.S.A.) I determined territories of male birds on the
      basis of male plumage characters and phases of the nesting cycle (2007) and on
      uniquely color-banded males (2008). I transferred locations of identified males
      to topographic maps. I counted all fledglings in territories from May to July
      each year. The model I tested may apply only to single-brooded species;
      therefore, I searched the literature to estimate the percentage of single-brooded
      species in North America. The breeding season of Cerulean Warblers was short-
      nearly all nests were initiated from mid-May to late June. Nest predation and
      brood parasitism were primary and rare causes of nest failure, respectively.
      Significantly fewer Cerulean Warblers fledged from parasitized than from
      nonparasitized nests. Fledgling survival required to maintain the population size
      was well above previously published values for Neotropical migrants. Single
      brooded species comprise 62% of North American breeding bird species for which
      the number of broods per year is known; I believe my results may apply to these
      species. The consistency between identification of populations as sources or
      sinks on the basis of either model estimates or direct measurements suggests that
      a demographic model relying on within-season sampling of fecundity is adequate to
      determine population status of single-brooded avian populations. In addition, on
      the basis of results of previous studies, annual adult survival rate of the
      Cerulean Warbler is typical of parulid warblers that are not declining. Thus, low
      fecundity, here determined with different quantitative methods, can drive status
      of landbird species with high-observed survival.

PMID- 21967246
TI  - The optimization of biohydrogen production by bacteria using residual glycerol
      from biodiesel synthesis.
AB  - In this research the production of hydrogen by Klebsiella pneumoniae BLb01 using
      residual glycerol discharged from a biodiesel fuel production plant was
      investigated. Klebsiella pneumoniae BLb01 was isolated from a bacteria-rich
      sludge of an upflow anaerobic sludge blanket reactor (UASB) of a soybean
      processing plant. A Plackett-Burman design (P-B) and Response Surface Methodology
      (RSM) were employed to determine the optimal condition for enhanced hydrogen
      production. The maximal hydrogen production, which was 45.0 mol % and with 98% of
      glycerol degradation, was achieved with the optimized medium with the following
      composition: 30 g L(-1) glycerol; 3 g L(-1) yeast ex tract 3 g L(-1) K(2)HPO(4);
      1 g L(-1) KH(2)PO(4); temperature 39 degrees C and pH 9.0. These results show the
      ability of this new strain of effectively converting residual glycerol into value
      added energy products.

PMID- 21967247
TI  - Photodegradation of hexythiazox in different solvent systems under the influence
      of ultraviolet light and sunlight in the presence of TiO2, H2O2, and KNO3 and
      identification of the photometabolites.
AB  - The photodegradation of the carboxamide acaricide hexythiazox in three different
      solvent systems (aqueous methanolic, aqueous isopropanolic, and aqueous
      acetonitrilic solutions) in the presence of H(2)O(2), KNO(3), and TiO(2) under
      ultraviolet (UV) light (lambda(max) >= 250 nm) and sunlight (lambda(max) >=290
      nm) has been assessed in this work. The kinetics of photodecomposition of
      hexythiazox and the identification of photoproducts were carried out using liquid
      chromatography-mass spectrometry. The rate of photodecomposition of hexythiazox
      in different solvents followed first-order kinetics in both UV radiation and
      natural sunlight, and the degradation rates were faster under UV light than under
      sunlight. Hexythiazox was found to be more efficiently photodegraded in the
      presence of TiO(2) than in the presence of H(2)O(2) and KNO(3). Two major
      photoproducts were separated in pure form using column chromatography and
      identified according to IR, (1)H NMR, and mass spectral information as
      cyclohexylamine and 5-(4-chlorophenyl)-4-methylthiazolidin-2-one. Another nine
      photoproducts were identified according to LC-MS/MS spectral information. The
      plausible photodegradation pathways of hexythiazox were proposed according to the
      structures of the photoproducts.

PMID- 21967248
TI  - Letter to the editor--Response to 'How expanding voluntary non-remunerated blood
      donations would benefit patients, donors and healthcare systems?'--F. Rossi, R.
      Perry, J. de Wit,T. Evers & G. Follea, Vox Sanguinis DOI: 10.1111/j.1423
      0410.2011.01495.x.

PMID- 21967250
TI  - Differential expression analysis of balding and nonbalding dermal papilla
      microRNAs in male pattern baldness with a microRNA amplification profiling
      method.
AB  - BACKGROUND:   Male pattern baldness or androgenetic alopecia is a common disorder
      affecting almost 50% of men throughout their lifetime, with androgens and
      genetics having significant contributing aetiologies. In contrast to the positive
      regulatory effect of androgens on body hair growth, they are thought to alter
      scalp hair follicle behaviour pathophysiologically, leading to male pattern
      baldness. However, the exact mechanisms of this paradoxical action have not yet
      been elucidated. The role of microRNAs, a novel group of noncoding RNAs impacting
      almost every aspect of biology, health and human diseases, has been documented in
      hair follicle formation. In addition, their deregulation in cancer of the
      prostate, a target organ of androgens, has also been well established.
      OBJECTIVES: To investigate the possible contribution of microRNAs in the
      pathophysiology of male pattern baldness. METHODS: We initially screened microRNA
      expression profiles of balding and nonbalding hair follicle papillae with a
      sensitive microRNA cloning method, microRNA amplification profiling, and
      statistically analysed significant differentially expressed microRNAs in balding
      relative to nonbalding dermal papillae, with real-time polymerase chain reaction
      as a confirmatory method to quantify expression in eight individuals affected
      with the disorder. RESULTS:   We detected the significant upregulation of miR
      221, miR-125b, miR-106a and miR-410 in balding papilla cells. CONCLUSIONS:   We
      found four microRNAs that could participate in the pathogenesis of male pattern
      baldness. Regarding the strong therapeutic potential of microRNAs and the easy
      accessibility of hair follicles for gene therapy, microRNAs are possible
      candidates for a new generation of revolutionary treatments.

PMID- 21967249
TI  - A simplified immune suppression scheme leads to persistent micro-dystrophin
      expression in Duchenne muscular dystrophy dogs.
AB  - Highly abbreviated micro-dystrophin genes have been intensively studied for
      Duchenne muscular dystrophy (DMD) gene therapy. Following adeno-associated virus
      (AAV) gene transfer, robust microgene expression is achieved in murine DMD models
      in the absence of immune suppression. Interestingly, a recent study suggests that
      AAV gene transfer in dystrophic dogs may require up to 18 weeks' immune
      suppression using a combination of three different immune-suppressive drugs
      (cyclosporine, mycophenolate mofetil, and anti-dog thymocyte globulin). Continued
      immune suppression is not only costly but also may cause untoward reactions.
      Further, some of the drugs (such as anti-dog thymocyte globulin) are not readily
      available. To overcome these limitations, we developed a novel 5-week immune
      suppression scheme using only cyclosporine and mycophenolate mofetil. AAV vectors
      (either AV.RSV.AP that expresses the heat-resistant human alkaline phosphatase
      gene, or AV.CMV.MUDys that expresses the canine R16-17/H3/DeltaC microgene) at
      2.85*10(12) vg particles were injected into adult dystrophic dog limb muscles
      under the new immune suppression protocol. Sustained transduction was observed
      for nearly half year (the end of the study). The simplified immune suppression
      strategy described here may facilitate preclinical studies in the dog model.

PMID- 21967251
TI  - Self-repairing complex helical columns generated via kinetically controlled self
      assembly of dendronized perylene bisimides.
AB  - The dendronized perylene 3,4:9,10-tetracarboxylic acid bisimide (PBI),
      (3,4,5)12G1-3-PBI, was recently reported to self-assemble in complex helical
      columns containing tetramers of PBI as basic repeat unit. These tetramers contain
      a pair of two molecules arranged side-by-side and another pair in the next
      stratum of the column turned upside-down and rotated around the column axis.
      Intra- and intertetramer rotation angles and stacking distances are different. At
      high temperature, (3,4,5)12G1-3-PBI self-assembles via a thermodynamically
      controlled process in a 2D hexagonal columnar phase while at low temperature in a
      3D orthorhombic columnar array via a kinetically controlled process. Here, we
      report the synthesis and structural analysis, by a combination of differential
      scanning calorimetry, X-ray and electron diffraction, and solid-state NMR
      performed at different temperatures, on the supramolecular structures generated
      by a library of (3,4,5)nG1-3-PBI with n = 14-4. For n = 11-8, the kinetically
      controlled self-assembly from low temperature changes in a thermodynamically
      controlled process, while the orthorhombic columnar array for n = 9 and 8
      transforms from the thermodynamic product into the kinetic product. The new
      thermodynamic product at low temperature for n = 9, 8 is a self-repaired helical
      column with an intra- and intertetramer distance of 3.5 A forming a 3D monoclinic
      periodic array via a kinetically controlled self-assembly process. The complex
      dynamic process leading to this reorganization was elucidated by solid-state NMR
      and X-ray diffraction. This discovery is important for the field of self-assembly
      and for the molecular design of supramolecular electronics and solar cell.

PMID- 21967252
TI  - Wnt/beta-catenin signaling is critical for dedifferentiation of aged epidermal
      cells in vivo and in vitro.
AB  - Aged epidermal cells have the capacity to dedifferentiate into stem cell-like
      cells. However, the signals that regulate the dedifferentiation of aged epidermal
      cells remain unclear. Here, we provide evidence that Wnt/beta-catenin is critical
      for aged epidermal cell dedifferentiation in vivo and in vitro. Some aged
      epidermal cells in human ultrathin epidermal sheets lacking basal stem cells
      transplanted onto wounds dedifferentiated into stem cell-like cells that were
      positive for CK19 and beta1 integrin but negative for CK10. In addition, Wnt/beta
      catenin pathway was activated during this process. There was increased expression
      of Wnt-1, Wnt-4, Wnt-7a, beta-catenin, cyclin D1, and c-myc. Secreted frizzled
      related protein 1, a Wnt/beta-catenin pathway inhibitor, blocked
      dedifferentiation in vivo. Then, the activator, a highly specific glycogen
      synthase kinase (GSK)-3beta inhibitor, of Wnt/beta-catenin pathway was added to
      the culture medium of aged epidermal cells. Surprisingly, we found that the
      activator induced higher expression of CK19, beta1 integrin, Oct4, and Nanog
      proteins. The induced aged epidermal cells exhibited high colony-forming
      efficiency, long-term proliferative potential and could regenerate a skin
      equivalent (as do epidermal stem cells). These results suggested that activation
      of Wnt/beta-catenin pathway induced the dedifferentiation of aged epidermal
      cells, which suggest a new approach to generate epidermal stem cell-like cells.

PMID- 21967253
TI  - Strategies for successfully establishing a kidney transplant in a mouse model.
AB  - OBJECTIVES: Kidney transplant in mouse model is quite useful and valuable for
      studying transplant immunobiology. However, its technical complexity and high
      mortality have hindered widespread use. We sought to review and analyze the
      various techniques of kidney transplant in mice to prevent pitfalls and reduce
      complications. MATERIALS AND METHODS: We searched PubMed using the key words
      "kidney transplant" or "renal transplant," "mouse" or "mice," and "technique" or
      "model" for articles published between January 1973 and June 2010. We found a
      series of factors that were collected and analyzed, which may influence
      establishing a mouse kidney transplant model. RESULTS: A mouse kidney transplant
      model is practical for research. Mouse body weight, sex, animal strain, type of
      anesthesia, and type of flushing solution are relevant but do not determine a
      successful transplant. Warm and cold ischemia time should be less than 35 minutes
      and 2.5 hours. CONCLUSIONS: End-to-side vascular anastomosis and ureter-to
      bladder or bladder-to-bladder for ureter reconstruction is preferred for
      establishing a kidney transplant model in mice.

PMID- 21967254
TI  - Alemtuzumab preconditioning allows steroid-calcineurin inhibitor-free regimen in
      live-donor kidney transplant.
AB  - OBJECTIVES: This prospective study was designed to develop a steroid and
      calcineurin inhibitor-free regimen for kidney transplants using alemtuzumab.
      MATERIALS AND METHODS: A single dose of alemtuzumab (30 mg) was given
      preoperatively. Phase 1: Twenty-one patients were randomized into 2 groups; the
      tacrolimus (n=11) and the sirolimus groups (n=10). Steroids were given for 5
      days. Azathioprine (1 mg/kg) was added when white blood cells >= 4000
      cells/cm(3). Mean follow-up was 48 +/- 2.8 and 48.2 +/- 1.6 months for the
      tacrolimus and sirolimus groups. Phase 2: Twenty patients were included and the
      study design was modified. Tacrolimus was given for 2 months, and was replaced by
      sirolimus thereafter. The mean follow-up was 28.3 +/- 2.1 months. RESULTS: Phase
      1: Acute rejection episodes were encountered in 5 patients of the tacrolimus
      versus 2 cases in the sirolimus group (P = .44). Antibody-mediated rejection was
      diagnosed in 2 recipients in each group. Four patients were switched from
      sirolimus to tacrolimus owing to resistant rejection, significant proteinuria,
      persistent thrombocytopenia, lymphocele, and urinary leakage. One patient was
      shifted from tacrolimus to sirolimus owing to Kaposi sarcoma. Glomerular
      filtration rate was significantly higher in the sirolimus group. Currently, 14
      patients (8 tacrolimus, and 6 sirolimus) are steroid-free. One patient died from
      the tacrolimus group owing to fulminant hepatitis. Two grafts were lost in the
      sirolimus group versus 1 graft in the tacrolimus group. Phase 2: Five patients
      developed successfully treated borderline changes with no antibody-mediated
      rejection. Mean serum creatinine was 114.9 +/- 17.7 umol/L. Currently, 17
      patients are steroid free and 15 of them are calcineurin inhibitor-free as well.
      In this phase, only 1 patient died with a functioning graft. CONCLUSIONS: This
      clinical trial provides a good insight into a potentially effective steroid and
      calcineurin inhibitor-free protocol with the use of alemtuzumab induction in
      combination with sirolimus.

PMID- 21967255
TI  - Chronic graft dysfunction and improvement by cytokine response modifier a protein
      transfection.
AB  - OBJECTIVES: Cytokine response modifier A protein is a caspase inhibitor that
      inhibits caspase activity and protects cells from apoptosis. Chronic cyclosporine
      nephropathy is a significant cause of chronic graft dysfunction. We explored
      cytokine response modifier A protein-alleviated chronic cyclosporine nephropathy
      for ways of improving chronic graft dysfunction. MATERIALS AND METHODS: Cytokine
      response modifier A protein-transferring HK-2 cells were cultured with different
      concentrations of cyclosporine. Cytokine response modifier A protein mRNA and
      proteins were detected by real-time polymerase chain reaction and Western blot,
      cell viability was detected by (3-(4,5-Dimethylthiazol-2-yl)-2,5-
      diphenyltetrazolium bromide), and apoptosis was detected by flow cytometry.
      RESULTS: Cyclosporine caused a concentration-dependent and time-dependent loss of
      cell viability in HK-2 cells. Cytokine response modifier A protein mRNA was
      expressed at 48 and 72 hours (P < .05), while protein was detected at 72 hours.
      Cell viability in the cytokine response modifier A protein-transfected group was
      significantly greater than that of the control group when treated with 1 ug/mL,
      10 ug/mL, or 20 ug/mL cyclosporine at 24 or 48 hours (P < .05). The apoptosis in
      cytokine response modifier A protein-transfected cells was significantly lower
      than that of controls (P < .05). CONCLUSIONS: Cytokine response modifier A
      protein protects renal cells from cyclosporine injury by inhibiting activated
      caspases. Cytokine response modifier A protein transfection may improve chronic
      cyclosporine nephropathy and provide for improving chronic graft dysfunction.

PMID- 21967256
TI  - Evaluation of right versus left laparoscopic donor nephrectomy.
AB  - OBJECTIVES: With the advent of laparoscopic donor nephrectomy, there has been a
      general underuse of right laparoscopic donor nephrectomy versus left because of
      concerns regarding higher complication rates and poorer outcomes. We performed a
      retrospective analysis of our laparoscopic donor nephrectomy series with an
      emphasis on the side of the kidney retrieved and the outcomes of donors and
      recipients. MATERIALS AND METHODS: Data on 94 consecutive donor-recipient pairs
      (188 patients) were reviewed. All donor nephrectomies were performed by pure
      laparoscopy. There were 74 left laparoscopic donor nephrectomies and 20 right
      laparoscopic donor nephrectomies. Intraoperative parameters and graft outcome
      were recorded and the data were analyzed to compare right laparoscopic donor
      nephrectomy versus left laparoscopic donor nephrectomy using a computer software
      system. Follow-up ranged from 1 to 6 years (mean, 3.4 y). RESULTS: There were no
      significant differences in any intraoperative or postoperative parameters, except
      in a slightly higher warm ischemia time in right laparoscopic donor nephrectomy
      versus left laparoscopic donor nephrectomy, but this did not translate into an
      adverse effect on renal recovery. Acute graft rejection was observed in 2 of 74
      patients who had a left laparoscopic donor nephrectomy (2.7%) and none of the
      patients who had a right laparoscopic donor nephrectomy. Chronic graft loss was
      observed in 2 of 74 patients who had a left laparoscopic donor nephrectomy
      (2.7%); 1 of recurrent pyelonephritis and sepsis and 1 renal oxalosis. No graft
      losses were observed in any patient who had a right laparoscopic donor
      nephrectomy. Mean serum creatinine levels in recipients at 1, 3, 6, 9, and 12
      months were equivalent for right laparoscopic donor nephrectomy versus left
      laparoscopic donor nephrectomy; they were 120, 110, 110, 110, 110 umol/L, versus
      110, 110, 110, 110, 110 umol/L. (1.35, 1.21, 1.24, 1.21, 1.26 mg/dL versus 1.22,
      1.17, 1.17, 1.17, 1.23 mg/dL). CONCLUSIONS: This single center study demonstrates
      equivalent results with left laparoscopic donor nephrectomy and right
      laparoscopic donor nephrectomy with no adverse effects of right laparoscopic
      donor nephrectomy on donor-recipient outcome or renal function.

PMID- 21967257
TI  - Inguinal oblique incision as an alternative route to extract the kidney during
      laparoscopic donor nephrectomy.
AB  - OBJECTIVES: Evaluate the advantages of inguinal oblique incision in extracting
      the kidney during laparoscopic donor nephrectomy. MATERIALS AND METHODS: From
      April 2005 to June 2009, sixty-seven cases of transperitoneal laparoscopic live
      donor nephrectomies were performed at our hospital, all data were analyzed
      retrospectively. All donors were grouped as a test group (n=37, inguinal oblique
      incision) and a control group (n=30, paramidline or subcostal incision) according
      to graft retrieval incision selection. Donors were compared with regard to
      operative time and warm ischemia time, operative blood loss, hospital stay and
      cosmetic satisfaction. Recipients were compared with regard to graft function and
      1-year graft survival rate. RESULTS: All 67 cases of transperitoneal live-donor
      nephrectomies were successfully accomplished, without donor death, serious
      complications, and conversion to open surgery. There were no differences in mean
      operation time, mean blood loss, mean warm ischemic time, graft function, and 1
      year graft survival rate between the groups. But in the test group, the mean
      hospital stay was shorter, P < .01; and cosmetic satisfaction was higher P < .01.
      CONCLUSIONS: The inguinal oblique incision is a safe and practical graft
      retrieval incision in live-donor nephrectomies, and can be thought to be applied
      generally.

PMID- 21967258
TI  - Turkey's evaluation in kidney transplantation research.
AB  - OBJECTIVES: The objective this study is to evaluate the trend of Turkey's
      contribution in terms of number of publications included in the Science Citation
      Index Expanded in kidney transplantation between 1980 and 2009. MATERIALS AND
      METHODS: All scientific papers published included in Science Citation Index
      Expanded in the English language between 1980 and 2009 were analyzed using the
      "Web of Science." A general search was conducted using key words of "kidney
      transplantation," "renal transplantation," "kidney transplant," and "renal
      transplant." We analyzed these results using the "analyze" function of the
      software in terms of countries, documentation types, number in years of
      publications, journals, and institutes. We also used the same function separately
      analyze papers from Turkey in last 3 decades between 1980 and 1989, 1990 and
      1999, and 2000 and 2009 for statistical evaluation. RESULTS: In total, we found
      46 983 papers related to kidney transplant were published included in the Science
      Citation Index Expanded in the English language between 1980 and 2009. Overall,
      964 of those papers were from Turkey (2.05%). There were 12 papers from Turkey
      between 1980 and 1989, 200 papers between 1990 and 1999, and 752 papers between
      2000 and 2009. The rank of Turkey among other countries, ranked by the number of
      papers published, was 33 between 1980 and 1989 and 11 between 2000 and 2009.
      CONCLUSIONS: Turkey has shown a significant positive trend in publishing papers
      in the field of kidney transplantation-further evidence of the progress Turkey
      has made in its contributions to the field of kidney transplantation in recent
      decades.

PMID- 21967259
TI  - Liver transplantation in patients with hepatocellular carcinoma: a single-center
      experience.
AB  - OBJECTIVES: Liver transplantation has become one of the best treatment options
      for early hepatocellular carcinoma in cirrhosis. We sought to study the results
      of liver transplantation in patients with hepatocellular carcinoma and to
      evaluate the outcome of the patients. MATERIALS AND METHODS: The medical records
      of 256 recipients who underwent a liver transplantation from April 2001 to
      January 2010 were reviewed. One hundred seventy-six patients received their
      livers from deceased donors, and 80 received their livers from living donors.
      Fifty-two patients underwent liver transplantation for hepatocellular carcinoma.
      RESULTS: From April 2001 until now, 52 patients (20.3%) underwent liver
      transplantation for hepatocellular carcinoma. Eighteen patients (34.6%) were
      performed from living-related donors, and 34 (65.4%) were from deceased donors.
      The patients were 37 males and 15 females (median, 55 years old; age range, 5
      through 68 years). Model for end-stage liver disease score ranged from 6 to 40
      with a median of 14. All patients were within the Milan criteria by the
      preoperative evaluation. Hospital stay ranged from 6 to 338 days with a median 14
      days. Operating time ranged from 4 to 15 hours with a median 7.5 hours. Blood
      transfusion ranged from 0 to 19 units median 5 units. Thirty-four complications
      occurred in 23 patients (44.2%). Recurrence of hepatocellular carcinoma in 7
      patients (13.5%), of which recurrent cholangiocarcinoma was diagnosed in 3
      (5.7%), accidentally discovered in the explant. One deceased donor had hepatitis
      B core antibody positive. One explant showed macrovascular invasion. Sixteen
      patients died, 7 of 52 (13.5%) from hepatocellular carcinoma recurrence,
      including the 3 cases of accidental discovery of cholangiocarcinoma (5.7%).
      CONCLUSIONS: Apart from the common complications that can occur with any
      transplantation, liver transplantation remains the most-promising solution for
      patients with hepatocellular carcinoma among the available ones, and represents a
      cornerstone in managing hepatocellular carcinoma. It is the only acceptable
      option for complete eradication of both the disease and the predisposing factor.

PMID- 21967260
TI  - Cyclosporine level at the second hour in pediatric hematopoietic stem cell
      transplant patients.
AB  - In this retrospective study, cyclosporine levels at the second hour (C2 levels)
      were measured during oral cyclosporine intake in 28 pediatric hematopoietic stem
      cell transplant patients, and the relations between cyclosporine dosage and C0,
      C2 levels, C2/C0 ratio, and cyclosporine-related adverse effects were
      investigated. Cyclosporine levels at the second hour levels were found to be
      significantly lower in children younger than 7 years old, suggesting age-related
      differences in absorption and metabolism of the drug. There were statistically
      significant correlations of both C0 and C2 levels with blood creatinine values.
      In addition, a statistically significant negative relation was found between C0
      and C2 levels and serum potassium levels; this unexpected finding was attributed
      to multiple drug effects in the early posttransplant period. The common adverse
      effects of cyclosporine (gingival overgrowth, gynecomastia, and hypertrichosis)
      were also evaluated in this study, and no correlation was found between those
      adverse effects and C0, C2 levels, C2/C0 ratio, and cyclosporine dosage. In the
      present study, despite the highly significant correlation of C2 levels with renal
      and metabolic effects, in pediatric hematopoietic stem cell transplant patients,
      measurement of C2 levels as a standard practice did not provide an advantage over
      C0 monitoring. However, the preliminary results suggest that C2 level monitoring
      could be useful in selected patients with increased risk of renal toxicity or in
      states where a better estimation of gastrointestinal absorption is needed.

PMID- 21967261
TI  - Chronic myeloid leukemia within a year of kidney transplant with elevated
      alkaline phosphatase correlated with imatinib therapy.
AB  - The incidence of certain malignancies is significantly higher after organ
      transplant. However, there are rare reports of chronic myeloid leukemia in the
      posttransplant setting. The average reported interval between a transplant and
      the diagnosis of chronic myeloid leukemia is 44 months (range, 10- 96 mo). We
      report 2 patients with chronic myeloid leukemia within 1 year of a kidney
      transplant, which is significantly shorter than those previously reported. Both
      patients were receiving mycophenolate mofetil and tacrolimus for
      immunosuppression. They were treated with imatinib for chronic myeloid leukemia,
      and both patients demonstrated an isolated elevation of serum alkaline
      phosphatase that was directly correlated with imatinib. Despite a potential
      interaction between the 2 drugs, blood levels of tacrolimus and imatinib were not
      elevated during the course of treatment. Isolated elevation of alkaline
      phosphatase in this particular setting has not been reported previously.

PMID- 21967262
TI  - Simultaneous cytomegalovirus and Mycobacterium tuberculosis infection presenting
      as hemorrhagic colitis 3 years after a kidney transplant.
AB  - Cytomegalovirus is an important cause of colonic disease in solid organ
      transplant recipients. Although several reports have shown that simultaneous
      infection with other pathogens may aggravate the course of cytomegalovirus
      colitis, to our knowledge, no case of colitis caused by simultaneous
      cytomegalovirus and Mycobacterium tuberculosis has been previously reported. We
      describe a case of hemorrhagic colitis associated with simultaneous
      cytomegalovirus/ Mycobacterium tuberculosis infection in a 26-year-old woman, 38
      months after a kidney transplant. Initial results of histopathologic analyses of
      gastrointestinal biopsies showed that tuberculosis was the only cause of colitis,
      as no morphologic alteration suggestive of cytomegalovirus infection was observed
      on hematoxylin-eosin staining. However, further analysis with immunoperoxidase
      staining confirmed the clinical suspicion of cytomegalovirus infection. This
      report shows that cytomegalovirus/tuberculosis coinfection may be a cause of late
      onset colitis among solid organ transplant recipients. It also illustrates that
      coinfection with other pathogens may pose an additional challenge for diagnosing
      gastrointestinal cytomegalovirus disease.

PMID- 21967263
TI  - Liver transplant for mixed capillary-cavernous hemangioma masquerading as
      hepatocellular carcinoma in a patient with hepatocellular carcinoma.
AB  - Hemangioma is the most common benign tumor of the liver. Unlike cavernous
      hemangioma, hepatic capillary or mixed capillary-cavernous hemangioma is a rare
      type of tumor in adults. Clinical presentation of hemangioma may mimic that of
      hepatocellular carcinoma. Furthermore, radiologic features on computed tomography
      and magnetic resonance imaging may not be typical for hemangioma and can be
      confused with hepatocellular carcinoma. Symptomatic hemangiomas require some form
      of treatment, such as corticosteroids, interferon, radiation, arterial
      embolization, surgical resection, or liver transplant. In the present case study,
      we present a patient treated with liver transplant for hemangioma mimicking
      hepatocellular carcinoma. This case report illustrates the atypical imaging
      appearance of hemangioma and possible confusion it can cause in diagnosing
      hepatocellular carcinoma, especially in a hepatitis C carrier.

PMID- 21967264
TI  - CD40 ligand deficiency with grade III liver fibrosis, transplanted by a
      treosulphan-based conditioning regimen.
AB  - X-linked Hyper IgM is characterized by an absence of the CD40 ligand on activated
      T lymphocytes resulting in defects of both cellular and humoral immunity.
      Patients usually present with recurrent bacterial and opportunistic infections.
      Chronic liver disease is seen in about 75% of patients as a complication. Here,
      we report a 3.5-year-old boy with X-linked Hyper IgM referred to our clinic for
      bone marrow transplant. He was transplanted from an HLA-identical sibling donor
      using a new conditioning agent, treosulphan, together with cyclophosphamide.
      Since 6 months of age, he has had recurrent respiratory infections, and his XHIGM
      was diagnosed when he was 1.5 years old. The diagnosis was confirmed by sequence
      analysis of the CD40L gene. On physical examination, growth failure, bilateral
      fine crackles in both lungs, and hepatosplenomegaly were detected. The results of
      his liver function tests were abnormal, and a liver biopsy showed grade III
      fibrosis and compensated cirrhosis. After conditioning with treosulphan (12
      g/m(2)/d x 3 d) and cyclophosphamide (50 mg/kg/d x 4 d), bone marrow from his HLA
      identical sister was infused. CD40L expression on activated lymphocytes of the
      patient was 84% on day +21. His posttransplant period was uneventful. He is now
      at posttransplant 2 years, with full donor chimerism, and mild, chronic, graft
      versus-host disease on his tongue. In conclusion, treosulphan is a new agent for
      conditioning regimen with less toxicity in patients with severe liver disease.

PMID- 21967265
TI  - Postoperative right diaphragmatic hernia with enterothorax in live liver donors.

PMID- 21967266
TI  - Pityriasis lichenoides chronic after measles-mumps-rubella vaccination.

PMID- 21967267
TI  - Deciding where to attend: priming of pop-out drives target selection.
AB  - With attention and eye-movements humans orient to targets of interest. This
      orienting occurs faster when the same target repeats: priming of pop-out (PoP).
      While reaction times (RTs) can be important, PoP's real function could be to
      steer where to orient, a possibility underexposed in many current paradigms, as
      these predesignate a target to which to orient. In a novel procedure we
      intermixed pop-out trials (one oddball target, two identical distractors) with
      choice trials (one item of each kind) where observers freely chose an item to
      attend to. Pop-out trials strongly drove subsequent choice: observers typically
      chose the preceding target. Conversely, choice trials affected subsequent pop-out
      RTs. Conventional PoP measures correlated positively with our choice measures
      among observers, suggesting common mechanisms. Our results support PoP accounts
      centered on altered target priority, and underscore PoP's importance for visual
      exploration.

PMID- 21967268
TI  - The influence of adaptation and inhibition on the effects of onset asynchrony on
      auditory grouping.
AB  - Onset asynchrony is an important cue for auditory scene analysis. For example, a
      harmonic of a vowel that begins before the other components contributes less to
      the perceived phonetic quality. This effect was thought primarily to involve high
      level grouping processes, because the contribution can be partly restored by
      accompanying the leading portion of the harmonic (precursor) with a synchronous
      captor tone an octave higher, and hence too remote to influence adaptation of the
      auditory-nerve response to that harmonic. However, recent work suggests that this
      restoration effect arises instead from inhibitory interactions relatively early
      in central auditory processing. The experiments reported here have reevaluated
      the role of adaptation in grouping by onset asynchrony and explored further the
      inhibitory account of the restoration effect. Varying the frequency of the
      precursor in the range +/- 10% relative to the vowel harmonic (Experiment 1), or
      introducing a silent interval from 0 to 320 ms between the precursor and the
      vowel (Experiment 2), both produce effects on vowel quality consistent with those
      predicted from peripheral adaptation or recovery from it. However, there were
      some listeners for whom even the smallest gap largely eliminated the effect of
      the precursor. Consistent with the inhibitory account of the restoration effect,
      a contralateral pure tone whose frequency is close to that of the precursor is
      highly effective at restoring the contribution of the asynchronous harmonic
      (Experiment 3). When the frequencies match, lateralization cues arising from
      binaural fusion of the precursor and contralateral tone may also contribute to
      this restoration.

PMID- 21967269
TI  - Judgments relative to patterns: how temporal sequence patterns affect judgments
      and memory.
AB  - Six experiments studied relative frequency judgment and recall of sequentially
      presented items drawn from 2 distinct categories (i.e., city and animal). The
      experiments show that judged frequencies of categories of sequentially
      encountered stimuli are affected by certain properties of the sequence
      configuration. We found (a) a first-run effect whereby people overestimated the
      frequency of a given category when that category was the first repeated category
      to occur in the sequence and (b) a dissociation between judgments and recall;
      respondents may judge 1 event more likely than the other and yet recall more
      instances of the latter. Specifically, the distribution of recalled items does
      not correspond to the frequency estimates for the event categories, indicating
      that participants do not make frequency judgments by sampling their memory for
      individual items as implied by other accounts such as the availability heuristic
      (Tversky & Kahneman, 1973) and the availability process model (Hastie & Park,
      1986). We interpret these findings as reflecting the operation of a judgment
      heuristic sensitive to sequential patterns and offer an account for the
      relationship between memory and judged frequencies of sequentially encountered
      stimuli.

PMID- 21967270
TI  - Effects of spatial and selective attention on basic multisensory integration.
AB  - When participants respond to auditory and visual stimuli, responses to
      audiovisual stimuli are substantially faster than to unimodal stimuli (redundant
      signals effect, RSE). In such tasks, the RSE is usually higher than probability
      summation predicts, suggestive of specific integration mechanisms underlying the
      RSE. We investigated the role of spatial and selective attention on the RSE in
      audiovisual redundant signals tasks. In Experiment 1, stimuli were presented
      either centrally (narrow attentional focus) or at 1 of 3 unpredictable locations
      (wide focus). The RSE was accurately described by a coactivation model assuming
      linear superposition of modality-specific activation. Effects of spatial
      attention were explained by a shift of the evidence criterion. In Experiment 2,
      stimuli were presented at 3 locations; participants had to respond either to all
      signals regardless of location (simple response task) or to central stimuli only
      (selective attention task). The RSE was consistent with task-specific
      coactivation models; accumulation of evidence, however, differed between the 2
      tasks.

PMID- 21967271
TI  - Training experts: individuation without naming is worth it.
AB  - There is growing evidence that individuation experience is necessary for
      development of expert object discrimination that transfers to new exemplars.
      Individuation training in human studies has primarily used label association
      tasks where labels are learned at both the individual and more abstract (basic)
      level, and expertise criterion requires that individual-level judgments become as
      fast as basic-level judgments. However, there are training situations when the
      use of labels is not practical (e.g., with animals or some clinical populations).
      Moreover, labeling itself can facilitate object discrimination, thus it is
      unclear what role labels play in the acquisition of expertise in such training
      paradigms. Here, participants completed an online game that did not require
      labels in which they interacted with novel objects (Greebles) or control objects
      (Yufos). Games either required individuation or categorization. We then assessed
      the impact of this exposure on an abridged Greeble training paradigm. As
      expected, participants who played Yufo games or Greeble categorization games
      showed a significant basic-level advantage for Greebles in the abridged training
      paradigm, typical of novices. However, participants who played the Greeble
      identity game showed a reduced basic-level advantage, suggesting that
      individuation without labels may be sufficient to acquire perceptual expertise.

PMID- 21967272
TI  - The benefit of surface uniformity for encoding boundary features in visual
      working memory.
AB  - Using a change detection paradigm, the present study examined an object-based
      encoding benefit in visual working memory (VWM) for two boundary features (two
      orientations in Experiments 1-2 and two shapes in Experiments 3-4) assigned to a
      single object. Participants remembered more boundary features when they were
      conjoined into a single object of uniform color than when they were not bound
      together into an object. However, such an object-based benefit diminished or
      disappeared when those features occurred on different parts of an object, as
      defined by surface discontinuity or by negative minima of curvature. These
      results suggest that the number of boundary features that can be stored in VWM is
      influenced by the hierarchical structure of objects: surface uniformity
      facilitates the integration of two boundary features into a single object
      representation, but this integration is weakened when the features occur on
      different parts of an object.

PMID- 21967273
TI  - Context, not conflict, drives cognitive control.
AB  - Theories of cognitive control generally assume that perceived conflict acts as a
      signal to engage inhibitory mechanisms that suppress subsequent conflicting
      information. Crucially, an absence of conflict is not regarded as being a
      relevant signal for cognitive control. Using a cueing, a priming, and a Simon
      task, we provide evidence that conflict does not have this unique signal status:
      Encountering a conflict does not lead to behavioral adjustments on subsequent
      conflict trials, whereas encountering a nonconflict trial does lead to behavioral
      adjustments on subsequent nonconflict trials. We propose that this apparent role
      reversal can be explained by a mechanism that responds to both the presence and
      the absence of conflict, down-regulating the visuomotor system following
      conflict, and up-regulating it following nonconflict.

PMID- 21967274
TI  - Object-based control of attention is sensitive to recent experience.
AB  - How is attention guided by past experience? In visual search, numerous studies
      have shown that recent trials influence responses to the current trial. Repeating
      features such as color, shape, or location of a target facilitates performance.
      Here we examine whether recent experience also modulates a more abstract
      dimension of attentional control, object-based and location-based control.
      Participants performed a cued target discrimination task with stimuli presented
      on 2 rectangles. Response times to targets appearing in an uncued location on a
      cued rectangle were faster than to targets on the uncued rectangle, demonstrating
      an object-based attentional benefit. We investigated the object-based benefit on
      the current trial contingent on the cue-target relationship on the previous
      trial. The object-based benefit was significant only when the cued object
      contained the target on the previous trial, not when the uncued object contained
      the target. This effect of recent experience was not due to either the repetition
      of spatial cue-target location or the repetition of the response, but to
      adaptation to contingencies in the environment. Our results suggest a unifying
      view of attentional control that spans the concrete dimensions of control (e.g.,
      determining the relative importance of red vs. blue) to the abstract (determining
      the relative importance of objects vs. locations in space). Attention closely
      tracks the short time scale structure of the environment and automatically adapts
      to optimize performance to this structure.

PMID- 21967275
TI  - Distinguishing norm-based from exemplar-based coding of identity in children:
      evidence from face identity aftereffects.
AB  - Children's performance on face identification tests improves dramatically between
      age 4 and adolescence, yet the source of this improvement is controversial. We
      used face identity aftereffects to examine whether changes in the organization of
      face-space during childhood could be a source of this improvement. Specifically
      we tested whether 7- to 9-year-old children, like adults, show patterns of
      aftereffects predicted by coding facial identity relative to a norm or the
      patterns predicted by exemplar-based coding. Consistent with use of norm-based
      coding children's aftereffects were larger (a) for opposite than non-opposite
      adapt-test pairs equated for perceptual similarity, and (b) for adaptors far from
      the average than for adaptors closer to the average. In addition, face identity
      aftereffects were present by age 5, suggesting adult-like face-space properties
      by 5, though we did not conduct specific tests to distinguish norm-based from
      exemplar-based coding in this age group. We conclude that children's poor face
      identification skills cannot be attributed to a failure to use norm-based coding.

PMID- 21967276
TI  - Antimicrobial management and appropriateness of treatment of urinary tract
      infection in general practice in Ireland.
AB  - ABSTRACT:  BACKGROUND: Urinary tract infections (UTIs) are the second most common
      bacterial infections in general practice and a frequent indication for
      prescription of antimicrobials. Increasing concern about the association between
      the use of antimicrobials and acquired antimicrobial resistance has highlighted
      the need for rational pharmacotherapy of common infections in general practice.
      METHODS: Management of urinary tract infections in general practice was studied
      prospectively over 8 weeks. Patients presenting with suspected UTI submitted a
      urine sample and were enrolled with an opt-out methodology. Data were collected
      on demographic variables, previous antimicrobial use and urine samples.
      Appropriateness of different treatment scenarios was assessed by comparing
      treatment with the laboratory report of the urine sample. RESULTS: A total of 22
      practices participated in the study and included 866 patients. Bacteriuria was
      established for 21% of the patients, pyuria without bacteriuria for 9% and 70%
      showed no laboratory evidence of UTI. An antimicrobial agent was prescribed to
      56% (481) of the patients, of whom 33% had an isolate, 11% with pyuria only and
      56% without laboratory evidence of UTI. When taking all patients into account,
      14% patients had an isolate identified and were prescribed an antimicrobial to
      which the isolate was susceptible. The agents most commonly prescribed for UTI
      were co-amoxyclav (33%), trimethoprim (26%) and fluoroquinolones (17%). Variation
      between practices in antimicrobial prescribing as well as in their preference for
      certain antimicrobials, was observed. Treatment as prescribed by the GP was
      interpreted as appropriate for 55% of the patients. Three different treatment
      scenarios were simulated, i.e. if all patients who received an antimicrobial were
      treated with nitrofurantoin, trimethoprim or ciprofloxacin only. Treatment as
      prescribed by the GP was no more effective than treatment with nitrofurantoin for
      all patients given an antimicrobial or treatment with ciprofloxacin in all
      patients. Prescribing cost was lower for nitrofurantoin. Empirical treatment of
      all patients with trimethoprim only was less effective due to the higher
      resistance levels. CONCLUSIONS: There appears to be considerable scope to reduce
      the frequency and increase the quality of antimicrobial prescribing for patients
      with suspected UTI.

PMID- 21967277
TI  - Chemical tools for studying directed cell migration.
AB  - Cell migration is required for many physiological processes, including wound
      repair and embryogenesis, and relies on precisely orchestrated events that are
      regulated in a spatially and temporally controlled manner. Most traditional
      approaches for studying migration, such as genetic methods or the use of chemical
      inhibitors, do not offer insight into these important components of protein
      function. However, chemical tools, which respond on a more rapid time scale and
      in localized regions of the cell, are capable of providing more detailed, real
      time information. This Review describes these recent approaches to investigate
      cell migration and focuses on proteins that are activated by light or small
      molecules, as well as fluorescent sensors of protein activity.

PMID- 21967278
TI  - Dopamine D1 receptor-mediated intracellular responses in the hypothalamus after
      co-administration of caffeine with MDMA.
AB  - Markers of dopamine D(1)  receptor activation were determined to elucidate
      intracellular mechanisms associated with the combined effects of caffeine and 3,4
      methylenedioxymethamphetamine (MDMA), reported previously to produce increased
      toxicity, when compared with either drug alone. Caffeine (10 mg/kg) and MDMA (15
      mg/kg) were administered to male Sprague Dawley rats alone and in combination.
      One hour after drug administration, core body temperature and phosphorylation of
      the dopamine D(1) -related intracellular markers, cAMP response element binding
      protein (CREB), the dopamine and c-AMP-regulated phosphoprotein of 32 kDa (DARPP
      32) and expression of the immediate early gene and cellular activation marker c
      fos were determined in the hypothalamus. Co-administration of caffeine with MDMA
      increased core body temperature when compared with MDMA or caffeine treatment
      alone. Pre-treatment with the dopamine D(1)  receptor antagonist SCH 23390 (1
      mg/kg, i.p.), 30 min. prior to caffeine and MDMA administration, produced a
      hypothermic response to MDMA that was unaffected by caffeine. Co-administration
      of caffeine with MDMA increased p-CREB, p-DARPP-32 and c-fos expression when
      compared with either treatment alone. Pre-treatment with SCH-23390 attenuated the
      changes in p-CREB, p-DARPP and c-fos. The results show an enhanced intracellular
      response when caffeine is combined with MDMA but not with either agent alone
      suggestive of synergistic intracellular actions convergent on a dopamine D(1) 
      receptor signalling pathway. A dopamine-related synergy associated with the
      combined administration of caffeine and MDMA may have important use and safety
      implications for recreational drug users.

PMID- 21967279
TI  - Electropalatographic specification of Croatian fricatives /s/ and /z/.
AB  - Electropalatographic specification of alveolar fricatives in Croatian is aimed at
      providing speech therapists with normative data about the range of acceptable
      productions of /s/ and /z/ in adult speakers of Croatian. Four variables were
      analysed: place of articulation, total contact, groove width and hold phase
      duration. Intra- and inter-speaker variability for each variable was analysed.
      Lingual palatal cues for voicing difference were also quantified and discussed.
      Results show that Croatian /s/ and /z/ are alveolar and not dental as previously
      reported. The comparison between the voiced and the voiceless fricative shows
      that durational measures provide the best differentiation. The voiceless
      counterpart is significantly longer. The difference between voiced and voiceless
      is also found in the total contact, with /z/ having more contact in the anterior
      four rows of electrodes, while /s/ has more contact in the posterior four rows of
      electrodes. This difference is also reflected in the anterior and the posterior
      groove widths. Possibilities of using these results as normative data for the
      diagnosis and treatment of atypical articulation of /s/ and /z/ are discussed.

PMID- 21967280
TI  - Conformational selection in the recognition of phosphorylated substrates by the
      catalytic domain of human Pin1.
AB  - Post-translational phosphorylation and the related conformational changes in
      signaling proteins are responsible for regulating a wide range of subcellular
      processes. Human Pin1 is central to many of these cell signaling pathways in
      normal and aberrant subcellular processes, catalyzing cis-trans isomerization of
      the peptide omega-bond in phosphorylated serine/threonine-proline motifs in many
      proteins. Pin1 has therefore been identified as a possible drug target in many
      diseases, including cancer and Alzheimer's. The effects of phosphorylation on
      Pin1 substrates, and the atomistic basis for Pin1 recognition and catalysis, are
      not well understood. Here, we determine the conformational consequences of
      phosphorylation on Pin1 substrate analogues and the mechanism of recognition by
      the catalytic domain of Pin1 using all-atom molecular dynamics simulations. We
      show that phosphorylation induces backbone conformational changes on the peptide
      substrate analogues. We also show that Pin1 recognizes specific conformations of
      its substrate by conformational selection. Furthermore, dynamical correlated
      motions in the free Pin1 enzyme are present in the enzyme of the enzyme-substrate
      complex when the substrate is in the transition state configuration, suggesting
      that these motions play significant roles during catalytic turnover. These
      results provide a detailed atomistic picture of the mechanism of Pin1 recognition
      that can be exploited for drug design purposes and further our understanding of
      the synergistic complexities of post-translational phosphorylation and cis-trans
      isomerization.

PMID- 21967281
TI  - Move for change part I: a European survey evaluating the impact of the EPDA
      Charter for People with Parkinson's disease.
AB  - BACKGROUND AND PURPOSE: The 1997 European Parkinson's Disease Association's
      (EPDA) Charter for People with Parkinson's disease (PD) outlines their rights in
      terms of standards of care. It states that all patients have the right to: be
      referred to a doctor with a special interest in PD; receive an accurate
      diagnosis; have access to support services; receive continuous care; and take
      part in managing their illness. Move for Change is a three-part series of pan
      European patient surveys based on this Charter. METHODS: This first survey,
      consisting of 23 questions, focusing on the initial two points of the Charter,
      was administered online through the EPDA and affiliated patient associations' Web
      sites. Of 2149 forms received from 35 European countries, 2068 (96.2%) were
      analyzed, with the remainder excluded, mainly due to incomplete responses.
      RESULTS: The majority of patients were diagnosed within 2 years from the onset of
      first symptoms (82.7%; range, <1 year to >=5 years). In relation to diagnosis
      delivery, 45.3% of patients stated that it was 'poor' or 'very poor'. During the
      2 years following diagnosis, 43.8% of respondents had never seen a PD specialist.
      Care was usually overseen by generically active neurologists (92.5%) or family
      doctors (81.0%), with considerable overlap between the two. CONCLUSIONS:   These
      data highlight challenges that patients with PD face during the period of
      diagnosis, despite introduction of the Charter. These findings can assist
      healthcare professionals and policy makers in improving the level of care for
      patients and their families across Europe, and we offer suggestions about how
      this can be achieved.

PMID- 21967282
TI  - Changes in emotional state modulate neuronal firing rates of human speech motor
      cortex: a case study in long-term recording.
AB  - In many brain areas, modulations in neuronal firing rates are thought to code
      information. However, in electrophysiological recording experiments, especially
      recordings in human patients, the type of information that is coded by a neuron's
      discharge patterns is often not known, or difficult to determine. From our long
      experience with chronic recordings in humans, we have come to suspect that such
      unexplained modulations in firing rates are often due to state changes in the
      subject. We here present two case studies, with extensive data in one subject to
      illustrate the point that a change in the subject's emotions, such as sudden
      fear, surprise, or happiness, may trigger substantial changes in firing rates.

PMID- 21967283
TI  - Functional reorganization of the auditory pathways following late callosotomy.
AB  - Injuries at various levels of the auditory system have been shown to lead to
      functional reorganization of the auditory pathways. In particular, it has
      recently been shown that such reorganization can occur in callosal agenesis. The
      pattern of cortical activity following callosotomy is however still unknown, but
      behavioral results suggest that it could be significantly different from that
      observed in callosal agenesis. We aimed to confirm this hypothesis by
      investigating fMRI responses to complex sounds presented binaurally and
      monaurally in a callosotomized patient. In the binaural condition, the
      callosotomized subject showed patterns of auditory cortical activation that were
      similar to those of neurologically intact individuals. However, in both monaural
      conditions, the callosotomized individual showed a significant increase of the
      asymmetries favoring the contralateral pathways. Such patterns of cortical
      responses are only partially consistent with the results obtained from callosal
      agenesis subjects using the exact same procedure. Indeed, the latter show
      differences compared with normals in both binaural and monaural conditions. These
      findings provide neurological evidence that callosotomy could lead to distinctive
      functional reorganization of the human auditory pathways.

PMID- 21967284
TI  - Myocardial performance index and atrial ejection force in patients with
      Duchenne's muscular dystrophy.
AB  - BACKGROUND: Progressive movement limitation in patients with Duchenne's muscular
      dystrophy (DMD) may mask the onset of cardiac involvement. We aimed to determine
      whether myocardial performance index (MPI), either by conventional Doppler (CD)
      or tissue Doppler imaging (TDI), could detect subclinical myocardial dysfunction
      in DMD patients. Furthermore, we assessed the atrial ejection force (AEF) to
      evaluate possible existence of latent diastolic dysfunction. METHOD: Twenty DMD
      patients without signs and symptoms of cardiac impairment and 20 age matched
      control group enrolled into the study. MPI for right ventricle and left ventricle
      (LV) was assessed with CD and TDI for comparison. RESULTS: No significant
      difference was detected in ejection fraction, fractional shortening, and AEF
      between two groups. CD derived MPI was higher for both ventricles in the patients
      (P < 0.0001). Moreover, the TDI derived MPI were significantly higher in the
      patients in mitral, tricuspid, and septal views (P < 0.0001). A significant
      decrease of mitral myocardial systolic wave velocity was detected in the
      patients, in favor of early involvement of the posterobasal LV myocardium. All
      acceleration and deceleration times' values for the late mitral inflow were
      higher whereas the rates were significantly lower in the patients. There was no
      significant difference between AEF of both groups. CONCLUSION: MPI might be a
      useful parameter for early detection of occult cardiac dysfunction in DMD
      patients when other simple and standard echocardiographic parameters are within
      the normal limits. Lack of atrial contribution in LV filling due to atrial
      contractile dysfunction may play a role in DMD cardiac dysfunction.

PMID- 21967286
TI  - Size-scaling in optical trapping of silicon nanowires.
AB  - We investigate size-scaling in optical trapping of ultrathin silicon nanowires
      showing how length regulates their Brownian dynamics, optical forces, and
      torques. Force and torque constants are measured on nanowires of different
      lengths through correlation function analysis of their tracking signals. Results
      are compared with a full electromagnetic theory of optical trapping developed in
      the transition matrix framework, finding good agreement.

PMID- 21967285
TI  - Identification and subtyping of Francisella by pyrosequencing and signature
      matching of 16S rDNA fragments.
AB  - AIMS: To analyse the V1 region of the 16S rDNA gene by a universal pyrosequencing
      protocol to identify and subtype Francisella in 31 strains from a repository
      collection and 96 patient isolates. METHODS AND RESULTS: Pyrosequencing was used
      to determine the nucleotide sequence of PCR amplification products of the
      variable region (V1) of the 16S rDNA from 31 repository strains and 96 isolates
      from Swedish patients with ulceroglandular tularaemia. Pyrosequencing resulted in
      a 37 nucleotide sequence, specific for Francisella sp., for all repository
      strains and patient samples analysed. In addition, the isolates could be divided
      into two groups based on the analysis of a single nucleotide polymorphism in the
      sequence: one group included Francisella tularensis ssp. tularensis, ssp.
      holarctica and ssp. mediasiatica, whereas the other group included Francisella
      tularensis ssp. novicida and other species of Francisella. The analysis of
      samples taken from patients suffering from ulceroglandular tularaemia revealed
      that all isolates belonged to the first group comprising subspecies of F.
      tularensis virulent for humans. CONCLUSIONS: The pyrosequencing analysis of the
      16S rDNA V1 is a useful molecular tool for the rapid identification of suspected
      isolates of Francisella sp. in clinical or environmental samples. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Virulent F. tularensis ssp. causing ulceroglandular
      tularaemia, or those with a potential to be used in a bioterrorism event, could
      rapidly be discriminated from subspecies less virulent for humans.

PMID- 21967287
TI  - Synthesis of novel nucleoside 5'-triphosphates and phosphoramidites containing
      alkyne or amino groups for the postsynthetic functionalization of nucleic acids.
AB  - A series of novel nucleoside 5'-triphosphates and phosphoramidites containing
      alkyne or amino groups for the postsynthetic functionalization of nucleic acids
      were designed and synthesized. For this purpose, the new 3-aminopropoxypropynyl
      linker group was used. It contains two alternative functional capabilities: an
      amino group for the reaction of amino-alkynyl-modified oligonucleotides with
      corresponding activated esters and an alkyne group for the copper(I)-catalyzed
      azide-alkyne cycloaddition (CuAAC) reaction. It was shown that a variety of
      methods of the attachment of the new linker can be used to synthesize a diversity
      of modified pyrimidine nucleosides.

PMID- 21967288
TI  - Synthesis and biological activity of the nucleoside analogs based on
      polyfluoroalkyl-substituted 1,2,3-triazoles.
AB  - This paper offers the results of a synthesis and study of cytotoxicity and the
      anti-Epstein-Barr virus (EBV) activity of new 2-deoxy-2-chloro-pyranosyl
      derivatives of 4-tosyl-5-trifluoromethyl-1,2,3-triazole obtained via the addition
      reaction of the corresponding 2-N-chlorotriazole to the double bond of 3,4,6-tri
      O-acetyl-D-glucal. Nucleoside mimetics, derivatives of 4-tosyl-5-polyfluoroalkyl
      1,2,3-triazoles containing fragments of 3-chloro-tetrahydrofuran, 3-chloro
      tetrahydropyran, tetrahydropyran, dihydrofuran, dihydropyran, or acyclic
      substituents, were also studied. Evaluation of cytotoxicity (trypan blue and MTT
      methods) and anti-EBV activity (polymerase chain reaction (PCR) method) showed
      high selectivity indices for the compounds 4a, 4b, 5b, 6, and 8. A total of 15
      novel compounds were examined in this study.

PMID- 21967289
TI  - Synthesis of novel 6'-spirocyclopropyl-5'-norcarbocyclic adenosine phosphonic
      Acid analogues as potent anti-hiv agents.
AB  - Novel 5'-norcarbocyclic adenosine phosphonic acid analogues with 6'
      electropositive moiety such as spirocyclopropane were designed and synthesized
      from the commercially available diethylmalonate 5. Regioselective Mitsunobu
      reaction proceeded in the presence of an allylic functional group at a low
      reaction temperature in polar cosolvent [dimethylformamide (DMF)/1,4-dioxane] to
      give purine analogue 15. To improve cellular permeability and enhance the anti
      human immunodeficiency virus (HIV) activity of this phosphonic acid, a SATE
      phosphonodiester nucleoside prodrug 23 was prepared. The synthesized adenosine
      phosphonic acids analogues 18-21 and 23 were subjected to antiviral screening
      against HIV-1.

PMID- 21967290
TI  - Design and synthesis of carbocyclic versions of furanoid nucleoside phosphonic
      Acid analogues as potential anti-hiv agents.
AB  - Novel 5'-norcarbocyclic adenine and guanine phosphonic acid analogues with 6',6'
      difluorine moiety were designed and synthesized from commercially available
      epichlorohydrin 5. A regioselective Mitsunobu reaction successfully proceeded
      from an allylic functional group 16b at low reaction temperature in polar
      cosolvent to give purine phosphonate analogues 17 and 24, respectively. The
      purine nucleoside phosphonate and phosphonic acid analogues were subjected to
      antiviral screening against HIV-1. Adenine analogue 21 and its SATE prodrug 29
      show significant anti-HIV activity in MT-4 cell lines.

PMID- 21967291
TI  - Nitrophenylboronic acids as highly chemoselective probes to detect hydrogen
      peroxide in foods and agricultural products.
AB  - Hydrogen peroxide is commonly used in the food processing industry as a chlorine
      free bleaching and sterilizing agent, but excessive amounts of residual hydrogen
      peroxide have led to cases of food poisoning. Here we describe the development of
      a novel nonenzymatic colorimetric method for the determination of residual
      hydrogen peroxide in foods and agricultural products. Nitrophenylboronic acids
      chemoselectively react with hydrogen peroxide under alkaline conditions to
      produce yellow nitrophenolates. Of the three nitrophenylboronic acid isomers
      tested, the p-isomer displayed the highest sensitivity for hydrogen peroxide and
      the fastest reaction kinetics. The reaction product, p-nitrophenolate, has an
      absorption maximum at 405 nm and a good linear correlation between the hydrogen
      peroxide concentration and the A(405) values was obtained. We successfully
      applied this convenient and rapid method for hydrogen peroxide determination to
      samples of dried bean curds and disposable chopsticks, thereby demonstrating its
      potential in foods and agricultural industries.

PMID- 21967292
TI  - Knowledge gain and behavioral change in citizen-science programs.
AB  - Citizen-science programs are often touted as useful for advancing conservation
      literacy, scientific knowledge, and increasing scientific-reasoning skills among
      the public. Guidelines for collaboration among scientists and the public are
      lacking and the extent to which these citizen-science initiatives change behavior
      is relatively unstudied. Over two years, we studied 82 participants in a three
      day program that included education about non-native invasive plants and
      collection of data on the occurrence of those plants. Volunteers were given
      background knowledge about invasive plant ecology and trained on a specific
      protocol for collecting invasive plant data. They then collected data and later
      gathered as a group to analyze data and discuss responsible environmental
      behavior with respect to invasive plants. We tested whether participants without
      experience in plant identification and with little knowledge of invasive plants
      increased their knowledge of invasive species ecology, participation increased
      knowledge of scientific methods, and participation affected behavior. Knowledge
      of invasive plants increased on average 24%, but participation was insufficient
      to increase understanding of how scientific research is conducted. Participants
      reported increased ability to recognize invasive plants and increased awareness
      of effects of invasive plants on the environment, but this translated into little
      change in behavior regarding invasive plants. Potential conflicts between
      scientific goals, educational goals, and the motivation of participants must be
      considered during program design.

PMID- 21967293
TI  - Different in vivo reactivity profile in health care workers and patients with
      spina bifida to internal and external latex glove surface-derived allergen
      extracts.
AB  - BACKGROUND: Allergy to natural rubber latex is a well-recognized health problem,
      especially among health care workers and patients with spina bifida. Despite
      latex sensitization being acquired in health institutions in both health care
      workers and patients with spina bifida, differences in allergen sensitization
      profiles have been described between these two risk groups. OBJECTIVE: To
      investigate the in vivo reactivity of health care workers and patients with spina
      bifida to extracts of internal and external surfaces of latex gloves and also to
      specific extracts enriched in major allergens for these risk groups. METHODS:
      Gloves from different manufacturers were used for protein extraction, and salt
      precipitation and hydrophobic interaction chromatography (HIC) were applied to
      obtain the enriched latex extracts. The major latex allergens were quantified by
      an enzyme immunoassay. The extracts obtained were tested in 14 volunteers using
      skin prick tests (SPT). RESULTS: Latex glove extracts enriched in the hydrophobic
      allergens that are most often seen in patients with spina bifida were obtained by
      selective precipitation, whereas HIC produced extracts enriched in the
      hydrophilic allergens commonly found in health care workers. The health care
      workers had positive SPTs to glove extracts from internal surfaces and to the
      hydrophilic allergen-enriched extracts. By contrast, patients with spina bifida
      had larger skin reactions both to external glove extracts and to the extracts
      enriched with the hydrophobic major allergens for this risk group. Despite the
      protein concentration of these extracts being less than half the concentration of
      the commercial extract, the weal-and-flare reactions were of similar magnitude.
      CONCLUSION: Using novel latex extracts, our study showed a different in vivo
      reactivity pattern in health care workers and in patients with spina bifida to
      extracts of the internal and external surfaces of gloves, which suggests that
      sensitization may occur by different routes of exposure, and that this influences
      the allergen reactivity profiles of these risk groups.

PMID- 21967294
TI  - The mind and heart (literally) of the negotiator: personality and contextual
      determinants of experiential reactions and economic outcomes in negotiation.
AB  - The authors developed and tested a model proposing that negotiator personality
      interacts with the negotiation situation to influence negotiation processes and
      outcomes. In 2 studies, the authors found that negotiators high in agreeableness
      were best suited to integrative negotiations and that negotiators low in
      agreeableness were best suited to distributive negotiations. Consistent with this
      person-situation fit argument, in Study 1 the authors found that negotiators
      whose dispositions were a good fit to their negotiation context had higher levels
      of physiological (cardiac) arousal at the end of the negotiation compared with
      negotiators who were "misplaced" in situations inconsistent with their level of
      agreeableness, and this arousal was in turn related to increased economic
      outcomes. Study 2 replicated and extended the findings of Study 1, finding that
      person-situation fit was related to physiological (heart rate), psychological
      (positive affect), and behavioral activation (persistence) demonstrated during
      the negotiation, and these measures in turn were related to the economic outcomes
      achieved by participants.

PMID- 21967295
TI  - The validity of interpersonal skills assessment via situational judgment tests
      for predicting academic success and job performance.
AB  - This study provides conceptual and empirical arguments why an assessment of
      applicants' procedural knowledge about interpersonal behavior via a video-based
      situational judgment test might be valid for academic and postacademic success
      criteria. Four cohorts of medical students (N = 723) were followed from admission
      to employment. Procedural knowledge about interpersonal behavior at the time of
      admission was valid for both internship performance (7 years later) and job
      performance (9 years later) and showed incremental validity over cognitive
      factors. Mediation analyses supported the conceptual link between procedural
      knowledge about interpersonal behavior, translating that knowledge into actual
      interpersonal behavior in internships, and showing that behavior on the job.
      Implications for theory and practice are discussed.

PMID- 21967296
TI  - Intentional response distortion on personality tests: using eye-tracking to
      understand response processes when faking.
AB  - Intentional response distortion or faking among job applicants completing
      measures such as personality and integrity tests is a concern in personnel
      selection. The present study aimed to investigate whether eye-tracking technology
      can improve our understanding of the response process when faking. In an
      experimental within-participants design, a Big Five personality test and an
      integrity measure were administered to 129 university students in 2 conditions: a
      respond honestly and a faking good instruction. Item responses, response
      latencies, and eye movements were measured. Results demonstrated that all
      personality dimensions were fakeable. In support of the theoretical position that
      faking involves a less cognitively demanding process than responding honestly, we
      found that response times were on average 0.25 s lower and participants had less
      eye fixations in the fake good condition [corrected]. However, in the fake good
      condition, participants had more fixations on the 2 extreme response options of
      the 5-point answering scale, and they fixated on these more directly after having
      read the question. These findings support the idea that faking leads to semantic
      rather than self-referenced item interpretations. Eye-tracking was demonstrated
      to be potentially useful in detecting faking behavior, improving detecting rates
      over and beyond response extremity and latency metrics.

PMID- 21967297
TI  - Impact of high-performance work systems on individual- and branch-level
      performance: test of a multilevel model of intermediate linkages.
AB  - We proposed and tested a multilevel model, underpinned by empowerment theory,
      that examines the processes linking high-performance work systems (HPWS) and
      performance outcomes at the individual and organizational levels of analyses.
      Data were obtained from 37 branches of 2 banking institutions in Ghana. Results
      of hierarchical regression analysis revealed that branch-level HPWS relates to
      empowerment climate. Additionally, results of hierarchical linear modeling that
      examined the hypothesized cross-level relationships revealed 3 salient findings.
      First, experienced HPWS and empowerment climate partially mediate the influence
      of branch-level HPWS on psychological empowerment. Second, psychological
      empowerment partially mediates the influence of empowerment climate and
      experienced HPWS on service performance. Third, service orientation moderates the
      psychological empowerment-service performance relationship such that the
      relationship is stronger for those high rather than low in service orientation.
      Last, ordinary least squares regression results revealed that branch-level HPWS
      influences branch-level market performance through cross-level and individual
      level influences on service performance that emerges at the branch level as
      aggregated service performance.

PMID- 21967298
TI  - Sporotrichoid-like calcinosis cutis and calcifications in vessel walls and
      eccrine sweat glands following intravenous infusion of calcium gluconate.

PMID- 21967299
TI  - The Danish Blood Donor Study: a large, prospective cohort and biobank for medical
      research.

PMID- 21967300
TI  - Sitting playfully: does the use of a centre of gravity computer game controller
      influence the sitting ability of young people with cerebral palsy?
AB  - PURPOSE: An investigative study to examine whether sitting ability could be
      improved through the use of a suite of computer games operated by leaning in one
      of four directions in a seated position. METHOD: Young people with cerebral palsy
      played with a suite of computer games controlled using a sitting platform that
      can detect changes in the distribution of pressure. A randomized cross-over trial
      with two periods of three months involving intervention or no intervention was
      used. Sitting ability was measured at the beginning and end of each period with
      participants acting as their own controls. RESULTS: Statistically significant
      improvements were seen in two elements of box sitting using the Chailey levels
      (shoulder girdle position and spinal profile) and in five elements of the Sitting
      Assessment for Children with Neuromotor Dysfunction across both reach and rest
      phases of the assessment. CONCLUSIONS: The study provides evidence to suggest
      that a meaningful and engaging therapeutic activity, such as using computer games
      controlled by leaning the upper body, can help to improve sitting ability in
      children with neuromotor dysfunction. Further work is required to understand
      fully what effects such activities have on the various components of sitting
      ability. [Box: see text].

PMID- 21967301
TI  - Transformative research in neural engineering: Foreword / editors' commentary
      (volume 3).

PMID- 21967302
TI  - Microfluidic and compartmentalized platforms for neurobiological research.
AB  - Methods to compartmentalize neurons allow distinct neuronal segments (i.e., cell
      bodies, axons, dendrites, or synapses) to be accessed, visualized, and/or
      manipulated. Compartmentalization has resulted in multiple studies that would not
      otherwise be possible in vivo or in traditional random cultures, such as
      investigations of axonal transport, biochemical analysis of axons, and axonal
      injury/regeneration. Chambers for compartmentalizing neurons were first developed
      for long projection peripheral neurons in the 1970s using machined Teflon
      dividers and relied on manually applied grease layers to spatially and
      fluidically separate distal axons from their cell bodies. More recently
      microfabrication and soft lithography techniques have been used to create
      compartmentalized microfluidic platforms, relying on microgrooves contained
      within a solid barrier through which axons and dendrites are able to extend, but
      not their cell bodies. These platforms are unique in their ability to culture
      central nervous system (CNS) neurons and allow high-resolution live imaging.
      These microfluidic platforms have allowed new investigations of axonal and
      synaptic biology in the CNS. Moreover, these microfluidic platforms offer
      improvements for other neural cell and tissue preparations. In this review we
      discuss traditional methods for compartmentalization, compartmentalized
      microfluidic platforms, and their use for neurobiology. Lastly, we discuss the
      use of these platforms for defining and manipulating synapses both
      pharmacologically and by electrical stimulation and recording.

PMID- 21967303
TI  - Neural tissue engineering and biohybridized microsystems for neurobiological
      investigation in vitro (Part 1).
AB  - Advances in neural tissue engineering have resulted in the development and
      implementation of three-dimensional (3-D) neural cellular constructs, which may
      serve as neurofidelic in vitro investigational platforms. In addition,
      interfacing these 3-D cellular constructs with micro-fluidic and/or micro
      electrical systems has created biohybridized platforms, providing unprecedented 3
      D microenvironmental control and allowing noninvasive probing and manipulation of
      cultured neural cells. Cells in the brain interact within a complex,
      multicellular environment with tightly coupled 3-D cell-cell/cell-extracellular
      matrix (ECM) interactions; yet most in vitro models utilize planar systems
      lacking in vivo-like ECM. As such, neural cultures with cells distributed
      throughout a thick (> 500 microm), bioactive extracellular matrix may provide a
      more physiologically relevant setting to study neurobiological phenomena than
      traditional planar cultures. This review presents an overview of 2-D versus 3-D
      culture models and the state of the art in 3-D neural cell-culture systems. We
      then detail our efforts to engineer a range of 3-D neural cellular constructs by
      systematically varying parameters such as cell composition, cell density, matrix
      constituents, and mass transport. The ramifications on neural cell survival,
      function, and network formation based on these parameters are specifically
      addressed. These 3-D neural cellular constructs may serve as powerful
      investigational platforms for the study of basic neurobiology, network
      neurophysiology, injury/disease mechanisms, pharmacological screening, or test
      beds for cell replacement therapies. Furthermore, while survival and growth of
      neural cells within 3-D constructs poses many challenges, optimizing in vitro
      constructs prior to in vivo implementation offers a sound bioengineering design
      approach.

PMID- 21967304
TI  - Neural tissue engineering for neuroregeneration and biohybridized interface
      microsystems in vivo (Part 2).
AB  - Neural tissue engineering offers tremendous promise to combat the effects of
      disease, aging, or injury in the nervous system. Here we review neural tissue
      engineering with respect to the design of living tissue to directly replace
      damaged or diseased neural tissue, or to augment the capacity for nervous system
      regeneration and restore lost function. This article specifically addresses the
      development and implementation of tissue engineered three-dimensional (3-D)
      neural constructs and biohybridized neural-electrical microsystems. Living 3-D
      neural constructs may be "pre-engineered" in vitro with controlled
      neuroanatomical and functional characteristics for neuroregeneration, to
      recapitulate lost neuroanatomy, or to serve as a nervous tissue interface to a
      device. One application being investigated is developing constructs of axonal
      tracts that, upon transplantation, may facilitate nervous system repair by
      directly restoring lost connections or by serving as a targeted scaffold to
      promote host regeneration by exploiting axon-mediated axonal regeneration. In
      another application, living nervous tissue engineered constructs are being
      investigated to biohybridize neural-electrical interface microsystems for
      functional integration with the nervous system. With this design, in vivo
      neuritic ingrowth and synaptic integration may occur with the living component,
      potentially exploiting a more natural integration with the nonorganic interface.
      Overall, the use of tissue engineered 3-D neural constructs may significantly
      advance regeneration or device-based deficit mitigation in the nervous system
      that has not been achieved by non-tissue engineering approaches.

PMID- 21967305
TI  - A map of minor groove shape and electrostatic potential from hydroxyl radical
      cleavage patterns of DNA.
AB  - DNA shape variation and the associated variation in minor groove electrostatic
      potential are widely exploited by proteins for DNA recognition. Here we show that
      the hydroxyl radical cleavage pattern is a quantitative measure of DNA backbone
      solvent accessibility, minor groove width, and minor groove electrostatic
      potential, at single nucleotide resolution. We introduce maps of DNA shape and
      electrostatic potential as tools for understanding how proteins recognize binding
      sites in a genome. These maps reveal periodic structural signals in yeast and
      Drosophila genomic DNA sequences that are associated with positioned nucleosomes.

PMID- 21967306
TI  - A study of the user's perception of economic value in nursing visits to primary
      care by the method of contingent valuation.
AB  - BACKGROUND: The identification of the attribution of economic value that users of
      a health system assign to a health service could be useful in planning these
      services. The method of contingent valuation can provide information about the
      user's perception of value in monetary terms, and therefore comparable between
      services of a very different nature. This study attempts to extract the economic
      value that the subject, user of primary care nursing services in a public health
      system, attributes to this service by the method of contingent valuation, based
      on the perspectives of Willingness to Pay (WTP) and Willingness to Accept
      [Compensation] (WTA). METHODS/DESIGN: This is an economic study with a
      transversal design. The contingent valuation method will be used to estimate the
      user's willingness to pay (WTP) for the care received from the primary care nurse
      and the willingness to accept [compensation] (WTA), were this service eliminated.
      A survey that meets the requisites of the contingent valuation method will be
      constructed and pilot-tested. Subsequently, 600 interviews will be performed with
      subjects chosen by systematic randomized sampling from among those who visit
      nursing at twenty health centers with different socioeconomic characteristics in
      the Community of Madrid. The characteristics of the subject and of the care
      received that can explain the variations in WTP, WTA and in the WTP/WTA ratio
      expressed will be studied. A theoretical validation of contingent valuation will
      be performed constructing two explanatory multivariate mixed models in which the
      dependent variable will be WTP, and the WTP/WTA relationship, respectively.
      DISCUSSION: The identification of the attribution of economic value to a health
      service that does not have a direct price at the time of use, such as a visit to
      primary care nursing, and the definition of a profile of "loss aversion" in
      reference to the service evaluated, can be relevant elements in planning,
      enabling incorporating patient preferences to health policy decision-making.

PMID- 21967307
TI  - Template engineering through epitope recognition: a modular, biomimetic strategy
      for inorganic nanomaterial synthesis.
AB  - Natural systems often utilize a single protein to perform multiple functions.
      Control over functional specificity is achieved through interactions with other
      proteins at well-defined epitope binding sites to form a variety of functional
      coassemblies. Inspired by the biological use of epitope recognition to perform
      diverse yet specific functions, we present a Template Engineering Through Epitope
      Recognition (TEThER) strategy that takes advantage of noncovalent, molecular
      recognition to achieve functional versatility from a single protein template.
      Engineered TEThER peptides span the biologic-inorganic interface and serve as
      molecular bridges between epitope binding sites on protein templates and selected
      inorganic materials in a localized, specific, and versatile manner. TEThER
      peptides are bifunctional sequences designed to noncovalently bind to the protein
      scaffold and to serve as nucleation sites for inorganic materials. Specifically,
      we functionalized identical clathrin protein cages through coassembly with
      designer TEThER peptides to achieve three diverse functions: the bioenabled
      synthesis of anatase titanium dioxide, cobalt oxide, and gold nanoparticles in
      aqueous solvents at room temperature and ambient pressure. Compared with previous
      demonstrations of site-specific inorganic biotemplating, the TEThER strategy
      relies solely on defined, noncovalent interactions without requiring any genetic
      or chemical modifications to the biomacromolecular template. Therefore, this
      general strategy represents a mix-and-match, biomimetic approach that can be
      broadly applied to other protein templates to achieve versatile and site-specific
      heteroassemblies of nanoscale biologic-inorganic complexes.

PMID- 21967308
TI  - The Journal of Sexual Medicine: sexual pain leader or vulvar disorder follower.

PMID- 21967310
TI  - Concomitant treatment of erectile dysfunction and postprostatectomy stress
      urinary incontinence.

PMID- 21967313
TI  - Electrical activity of corpus cavernosum during flaccidity and erection of the
      human penis: a new diagnostic method? Wagner G, Gerstenberg T, and Levin RJ.

PMID- 21967314
TI  - Effects of icariin on improving erectile function in streptozotocin-induced
      diabetic rats.
AB  - INTRODUCTION: Icariin has been shown to improve penile hemodynamics in animal
      models of erectile dysfunction from cavernous nerve injury and castration. The
      effects of icariin on penile hemodynamics in diabetic animals remain to be
      determined. Transforming growth factor beta1 (TGFbeta1) has been implicated in
      the pathogenesis of diabetes-related erectile dysfunction. AIM: The aim of this
      study was to investigate the effects of icariin in the penis of streptozotocin
      (STZ)-induced diabetic rat. METHODS: Two-month-old Sprague-Dawley male rats
      received one-time intraperitoneal (IP) STZ (60 mg/kg) or vehicle injection after
      a 16-hour fast. Three days later, the STZ-induced diabetic rats were randomly
      divided into four groups and were treated with daily gavage feedings of a 50:50
      mix of normal saline and dimethyl sulfoxide (DMSO) or icariin dissolved in DMSO
      at doses of 1, 5, and 10 mg/kg for 3 months. A positive control group underwent
      IP injection of saline followed by daily gavage of saline/DMSO solution.
      Treatment was stopped 1 week prior to functional assay and euthanasia. MAIN
      OUTCOME MEASURE: Penile hemodynamics was assessed by electrical stimulation of
      the cavernous nerves with real-time intracavernous pressure (ICP) measurement.
      After euthanasia, penile tissue was studied using immunohistochemistry, Western
      blot, and enzyme-linked immunosorbent assay (ELISA) to assess the nitric oxide
      cyclic guanosine monophosphate (NO-cGMP) and TGFbeta1/Smad2 signaling pathway.
      RESULTS: Diabetes attenuated ICP response in control animals. Untreated diabetic
      animals had decreased smooth muscle/collagen ratio and endothelial cell content
      in the corpora cavernosa; treatment with icariin partially attenuating these
      effects. Icariin-treated animals also had a significantly greater expression of
      nicotinamide adenine dinucleotide phosphate-positive nerves and the endothelial
      cell markers, von Willebrand factor (vWF), and platelet endothelial cell adhesion
      molecule-1 (PECAM). TGFbeta1/Smad2 signaling pathway was down-regulated in the
      penis from icariin-treated models relative to what was observed in negative
      control animals. CONCLUSION: Icariin treatment preserved penile hemodynamics,
      smooth muscle and endothelial integrity, and neuronal nitric oxide synthase
      expression in the penis of diabetic rats. Down-regulation of TGFbeta1/Smad2
      signaling pathway might mediate this effect.

PMID- 21967315
TI  - Errata by Fabre et al. in gepirone-ER treatment of hypoactive sexual desire
      disorder associated with depression in women.

PMID- 21967316
TI  - Patient highlights. Healthy lifestyle and sexuality.

PMID- 21967317
TI  - Normalisation of insulin-like growth factor-I does not improve insulin action in
      cirrhosis.
AB  - BACKGROUND & AIMS: Cirrhosis of the liver is characterised by insulin resistance
      and low levels of insulin-like growth factor I (IGF-I). Lack of IGF-I may
      contribute to this insulin resistance, as IGF-I increases insulin sensitivity.
      This study aimed to determine the effects of normalisation of IGF-I on insulin
      action in cirrhosis. METHODS: This article is a randomised sequence-crossover
      placebo controlled study. Eight patients with cirrhosis and eight controls were
      studied following treatment with IGF-I (50 MUg/kg twice daily) or saline. Insulin
      action, glucose utilisation and endogenous glucose production were measured
      during the euglycaemic hyperinsulinaemic clamp. RESULTS: The patients with
      cirrhosis had normal fasting glucose level, but increased levels of insulin (P <
      0.05) and C-peptide (P < 0.05). Insulin resistance resulted from a defect in
      glycogen synthesis, whereas insulin-mediated suppression of glucose production
      was unaltered. In cirrhosis, IGF-I treatment normalised free (from 0.07 +/- 0.01
      to 0.26 +/- 0.05 MUg/L) and total IGF-I (from 73 +/- 6 to 250 +/- 39 MUg/L),
      whereas in controls, the IGF-I level increased into the upper physiological range
      (free IGF-I from 0.23 +/- 0.02 to 0.61 +/- 0.06 MUg/L; total IGF-I from 200 +/-
      19 to 500 +/- 50 MUg/L) (all P-values < 0.05). In cirrhosis, IGF-I treatment did
      not change fasting glucose, insulin or C-peptide levels (P > 0.05). In the
      controls, insulin and C-peptide levels decreased (P < 0.05). IGF-I treatment did
      not improve insulin sensitivity in cirrhosis. CONCLUSIONS: Because normalisation
      of IGF-I levels did not affect insulin sensitivity lack of IGF-I is unlikely to
      result in insulin resistance in cirrhosis. IGF-I supplementation is therefore
      unlikely to improve insulin action in patients with cirrhosis.

PMID- 21967318
TI  - Percutaneous antegrade ureteral stent placement during pediatric robot-assisted
      laparoscopic pyeloplasty.
AB  - BACKGROUND AND PURPOSE: Robot-assisted laparoscopic pyeloplasty has become more
      widely used. Intraoperative placement and confirmation of ureteral stent position
      can be cumbersome with the robotic arms in place. We present a technique of
      percutaneous antegrade stent placement that is reliable with minimal morbidity.
      PATIENTS AND METHODS: A retrospective cohort study was performed. Patient
      demographics, radiographic imaging, intraoperative details, and surgical outcomes
      were abstracted from the medical record. A 14-gauge angiocatheter was placed
      through the abdominal wall. A ureteral stent was guided over a wire down the
      dismembered ureter. Stent position was confirmed by retrograde reflux of
      methylene blue. A urethral catheter was left in place for 12 to 36 hours.
      RESULTS: Twenty-nine patients (15 male, 14 female) were identified. Average age
      was 10 years. Average follow-up was 14 months. Fifteen left- and 14 right-sided
      procedures were performed. Two patients needed retrograde stent placement. Mean
      time to correctly position the stent was less than 5 minutes. Postoperatively,
      one patient had a urine leak managed by an indwelling urethral catheter and did
      not need percutaneous drainage. All stents were removed approximately 4 to 6
      weeks postoperatively. One patient had retrograde migration of the stent managed
      by ureteroscopy at the time of stent retrieval. CONCLUSIONS: Antegrade ureteral
      stent placement through a percutaneous angiocatheter, during robot-assisted
      laparoscopic pyeloplasty, is a rapid and effective technique. Intraoperative
      confirmation of stent position can be obtained, using methylene blue bladder
      distention, without repositioning the patient or undocking the surgical robot.

PMID- 21967319
TI  - Prospective randomized evaluation of gel mat foot pads in the endoscopic suite.
AB  - BACKGROUND AND PURPOSE: Several studies that compare open and laparoscopic
      procedures have demonstrated that the minimally invasive surgeon has greater
      musculoskeletal pain when compared with open surgeons. The purpose of our study
      was to demonstrate whether the use of the gel mat in the endoscopic setting
      offered any ergonomic benefit to the surgeon. MATERIALS AND METHODS: One hundred
      endoscopic procedures, by 11 different surgeons, were randomized intostudy (use
      of a gel mat) and control groups. Procedures included both percutaneous
      nephrolithotomies and ureteroscopies and were randomized without regard to the
      type or expected length of the procedure. All subjects completed a preoperative,
      intraoperative, immediate postoperative, and 24-hour postoperative questionnaire.
      During the procedures, an independent observer recorded the number of
      intraoperative stretches and positional changes because of discomfort. RESULTS:
      The mean preoperative metrics for the gel mat and no gel mat groups were similar
      with the exception of the <=60-minute group, whose members found the gel mat
      group starting with greater overall discomfort (1.7 vs 1.3, P=0.0273). In the
      <=60 minute group, gel mat use significantly decreased postoperative discomfort
      (P=0.0435) and improved postoperative energy (P=0.0411). In those procedures >60
      minutes, the gel mat improved postoperative discomfort and energy as well as the
      number of stretches and postural changes during the procedure. CONCLUSION:
      Application of gel mats in the endoscopic setting improves surgeon overall
      postoperative discomfort and energy in all cases. For cases >60 minutes duration,
      gel mats also decrease the number of stretches and postural changes from
      discomfort. Some of these salutary effects may translate into more efficient
      surgery and better patient outcomes.

PMID- 21967320
TI  - Recollection can be weak and familiarity can be strong.
AB  - The remember-know procedure is widely used to investigate recollection and
      familiarity in recognition memory, but almost all of the results obtained with
      that procedure can be readily accommodated by a unidimensional model based on
      signal-detection theory. The unidimensional model holds that remember judgments
      reflect strong memories (associated with high confidence, high accuracy, and fast
      reaction times), whereas know judgments reflect weaker memories (associated with
      lower confidence, lower accuracy, and slower reaction times). Although this is
      invariably true on average, a new 2-dimensional account (the continuous dual
      process model) suggests that remember judgments made with low confidence should
      be associated with lower old-new accuracy but higher source accuracy than know
      judgments made with high confidence. We tested this prediction--and found
      evidence to support it--using a modified remember-know procedure in which
      participants were first asked to indicate a degree of recollection-based or
      familiarity-based confidence for each word presented on a recognition test and
      were then asked to recollect the color (red or blue) and screen location (top or
      bottom) associated with the word at study. For familiarity-based decisions, old
      new accuracy increased with old-new confidence, but source accuracy did not
      (suggesting that stronger old-new memory was supported by higher degrees of
      familiarity). For recollection-based decisions, both old-new accuracy and source
      accuracy increased with old-new confidence (suggesting that stronger old-new
      memory was supported by higher degrees of recollection). These findings suggest
      that recollection and familiarity are continuous processes and that participants
      can indicate which process mainly contributed to their recognition decisions.

PMID- 21967321
TI  - Quality of life and psychological status of patients with pemphigus vulgaris
      using Dermatology Life Quality Index and General Health Questionnaires.
AB  - Pemphigus vulgaris with painful chronic blisters and/or erosions on skin and
      mucosa can impair quality of life (QOL). Therapeutic modalities in the long run
      can have additional negative impact. There are few studies that have focused on
      QOL of such patients except in treated cases. The aim of this study was to
      describe the effect of the disease per se on QOL before receiving treatment and
      evaluation of psychological status of the patients and its effect on their QOL. A
      total of 61 patients with newly diagnosed non-treated pemphigus vulgaris
      participated in the study. The Persian version of the Dermatology Life Quality
      Index (DLQI) questionnaire was used to evaluate their QOL and the 28-item General
      Health Questionnaire (GHQ-28) for their psychological status. In this study, the
      mean DLQI score was 10.9 +/- 6.9. QOL was worse in patients with nasal and
      pharynx involvement, with positive Nikolsky sign, patients with severe skin
      involvement and those who showed the symptom of itching. There was a negative
      correlation between DLQI score and duration of the disease. More than 77% of
      patients experienced anxiety and depression with more impaired QOL. In
      conclusion, pemphigus vulgaris is responsible for great alteration in QOL,
      especially in its severe form. The disease in its initial stage may have greater
      impact on the QOL. The high probability of anxiety and depression in these
      patients and its negative effect on QOL should be taken into account in the
      management of these patients right from the start of the treatment.

PMID- 21967322
TI  - Benefit of transfusion-related acute lung injury risk-minimization measures-
      German haemovigilance data (2006-2010).
AB  - OBJECTIVE: Based on the frequency of immune-mediated and non-immune-mediated
      transfusion-related acute lung injury (TRALI), the effect of risk-minimization
      measures was evaluated during a period of 5 years (2006-2010). Risk-minimization
      measures were implemented in 2008/2009, consisting of exclusion of female donors
      with a history of pregnancy or exclusion of female donors with human leucocyte
      antigen (HLA)/human neutrophil alloantigen (HNA) antibodies. METHODS: TRALI was
      confirmed according to the criteria of the International Haemovigilance Network.
      Based upon the results of donor testing of white-blood-cell antibodies (WBC-Ab)
      against HLA or HNAs, confirmed cases were classified as immune- or non-immune
      mediated TRALI. Reporting rates were calculated on the basis of the annually
      transfused blood components, and pre- and post-implementation periods were
      compared. RESULTS: In total, 60 immune-mediated (75%) and 20 non-immune-mediated
      (25%) TRALI reactions were confirmed. A total of 68 (64 women and four men)
      donors were involved: seven red-blood-cell concentrates donors (13%), six
      platelet concentrate donors (10%), and 48 fresh frozen plasma (FFP) donors (77%).
      The reporting rate of immune-mediated TRALI caused by FFP decreased continuously;
      from 12.71 per million units in 2006/2007 to 6.81 per million units in 2008/2009
      and no case in 2010. CONCLUSION: The comparison of the pre- and the post
      implementation period demonstrated a significantly reduced risk of TRALI events
      comparing 2006/2007 with 2010 (P-value: <0.01). Furthermore, no case of TRALI
      induced fatality occurred after the implementation of risk-minimization measures.

PMID- 21967323
TI  - The F-box protein CPR1/CPR30 negatively regulates R protein SNC1 accumulation.
AB  - Disease resistance (R) proteins, as central regulators of plant immunity, are
      tightly regulated for effective defense responses and to prevent constitutive
      defense activation under non-pathogenic conditions. Here we report the
      identification of an F-box protein CPR1/CPR30 as a negative regulator of an R
      protein SNC1 likely through SCF (Skp1-cullin-F-box) mediated protein degradation.
      The cpr1-2 (cpr30-1) loss-of-function mutant has constitutive defense responses,
      and it interacts synergistically with a gain-of function mutant snc1-1 and a bon1
      1 mutant where SNC1 is upregulated. The loss of SNC1 function suppresses the
      mutant phenotypes of cpr1-2 and cpr1-2 bon1-1, while overexpression of CPR1
      rescues mutant phenotypes of both bon1-1 and snc1-1. Furthermore, the amount of
      SNC1 protein is upregulated in the cpr1-2 mutant and down-regulated when CPR1 is
      overexpressed. The regulation of SNC1 by CPR1 is dependent on the 26S proteosome
      as a protease inhibitor MG132 stabilizes SNC1 and reverses the effect of CPR1 on
      SNC1. Interestingly, CPR1 is induced after infection of both virulent and
      avirulent pathogens similarly to the other negative defense regulator BON1. Thus,
      this study reveals a new mechanism in R protein regulation likely through protein
      degradation and suggests negative regulation as a critical component in fine
      control of plant immunity.

PMID- 21967324
TI  - Fatigue, depression, and health-related quality of life in patients with multiple
      sclerosis in Isfahan, Iran.
AB  - BACKGROUND AND PURPOSE: Quality of life (QoL) of patients with multiple sclerosis
      (MS) is worse than that of other chronic diseases. There is a need to examine the
      impact of fatigue and depression on the QoL independent of level of physical
      disability in MS. The aim of this study is to explore physical, psychological,
      and social aspects of health-related QoL (HRQoL) of MS patients in association
      with physical disability, fatigue, and depression. METHODS: In a cross-sectional
      study, 281 (63.4% women, 36.6% men) patients with MS participated in the study.
      The HRQoL was assessed by the Persian version of the multiple sclerosis quality
      of life (MSQoL-54) questionnaires. Other covariates included in the study were
      disease type, physical disability, fatigue, disease impact, and depression.
      RESULTS: In univariate analysis disease type, physical disability, fatigue,
      disease impact, and depression were significantly associated with both physical
      and mental health composite summaries of MSQoL-54. In multivariate regression
      analysis, patients' physical disability remained significantly associated with
      both components of MSQoL-54, whilst fatigue and depression were associated with
      physical and mental composite summaries, respectively. CONCLUSIONS: Our findings
      suggest that MS-related physical disability, fatigue, and depression affect the
      HRQoL of MS patients, independently of each other and other potential confounding
      factors. Effective interventions that target fatigue and depression may help
      improve the QoL of patients, regardless of their disease type and level of
      disability.

PMID- 21967325
TI  - Degradation of pentachlorophenol by potato polyphenol oxidase.
AB  - In this study, polyphenol oxidase (PPO) was extracted from commercial potatoes.
      Degradation of pentachlorophenol by potato PPO was investigated. The experimental
      results show that potato PPO is more active in weak acid than in basic condition
      and that the optimum pH for the reaction is 5.0. The degradation of
      pentachlorophenol by potato PPO reaches a maximum at 298 K. After reaction for 1
      h, the removal of both pentachlorophenol and total organic carbon is >70% with
      6.0 units/mL potato PPO at pH 5.0 and 298 K. Pentachlorophenol can be degraded
      through dechlorination and ring-opening by potato PPO. The work demonstrates that
      pentachlorophenol can be effectively eliminated by crude potato PPO.

PMID- 21967326
TI  - Congenitally corrected transposition of the great arteries with anomalous
      inferior vena cava drainage: multimodality imaging.
AB  - Atrioventricular discordance with ventricular-arterial discordance is a rare
      cardiac anomaly known as congenitally corrected transposition of the great
      arteries (CCTGA). This malformation has a prevalence of 0.4-0.6% of all
      congenital heart disease cases. Complete heart block develops in up to 30% of
      patients with CCTGA. We present the case of a 62-year-old woman diagnosed with
      CCTGA who, on echocardiography, had anomalous venous drainage where the inferior
      vena cava (IVC) bypassed the right atrium and drained into the azygos system.
      Complementary images with magnetic resonance imaging demonstrated the unique
      anatomical relationship between the IVC, azygos venous system, and the superior
      vena cava. 

PMID- 21967327
TI  - Developmental changes in the variability of tongue and lip movements during
      speech from childhood to adulthood: an EMA study.
AB  - This study investigated the developmental variability of lip and tongue movement
      in 48 children and adults. Motion of the tongue-tip, tongue-body and lower lip
      was recorded using electromagnetic articulography during productions of sentences
      containing /t/, /s/, /l/, /k/ and /p/. Four groups of speakers participated in
      the study: (1) aged 6-7 years; (2) 8-11 years; (3) 12-17 years; and (4) adults.
      The variation in distance, duration, speed, acceleration and deceleration of the
      articulators during single open-close speech movements was analysed, and the
      stability of multiple movement sequences was examined using the spatiotemporal
      index. The experimental findings revealed a gradual developmental progression
      from 6 years to adulthood. At adolescence, speakers continued to exhibit
      significantly more variable speech motor output compared to adult speakers. The
      observed developmental pattern suggests that attenuated, but important, changes
      in the speech motor system occurs from mid-childhood, through adolescence, to
      adulthood.

PMID- 21967328
TI  - Supramolecular networking of macrocycles based on exo-coordination: from discrete
      to continuous frameworks.
AB  - Macrocyclic ligands typically show high selectivity for specific metal ions and
      small molecules, and these features make such molecules attractive candidates for
      nanoscale chemical sensing applications. Crown ethers are macrocyclic structures
      with polyether linkages where the oxygen donors are often separated by an
      ethylene unit (-O-CH(2)-CH(2)-O-).  Because the oxygen lone pairs in crown-type
      macrocycles are directed inward, the preorganized macrocyclic cavity tends to
      form complexes where metals coordinate inside the cavity (endo-coordination).
      However, sulfur-containing macrocycles often demonstrate metal coordination
      outside of the cavity (exo-coordination). This coordination behavior results from
      the different torsion arrangements adopted by the X-CH(2)-CH(2)-X atom sequence
      (X = O, gauche; X = S, anti) in these molecules.  Exo-coordination is
      synthetically attractive because it would provide a means of connecting
      macrocyclic building blocks in diverse arrangements. In fact, exo-coordination
      could allow the construction of more elaborate network assemblies than are
      possible using conventional endocyclic coordination (which gives metal-in-cavity
      products). Exo-coordination can also serve as a tool for crystal engineering
      through the use of diverse controlling factors. Although challenges remain in the
      development of exo-coordination-based synthetic approaches and, in particular,
      for the architectural control of supramolecular coordination platforms, we have
      established several strategies for the rational synthesis of new
      metallosupramolecules.  In this Account, we describe our recent studies of the
      assembly of metallosupramolecules and coordination polymers based on sulfur
      containing macrocycles that employ simple and versatile exo-coordination
      procedures. Initially, we focus on the unusual topological products such as
      sandwich (1:2, metal-to-ligand), club sandwich (2:3), and cyclic oligomeric
      complexes as discrete network systems. The primary structures we achieve in these
      networked macrocycles are one to three dimensional coordination polymers based on
      homo- and heteronuclear metal systems. Using crystal engineering methods, we have
      also investigated variation in the donors, interdonor distances, ligand isomer
      structures, and the effect of counter anions on the chemical and physical
      properties of the products.  Understanding the relationship between structure and
      function in these exo-coordination products is an important step in the design of
      these new supramolecules for practical applications. We investigated the
      photophysical properties of the exocyclic complexes and a chromogenic macrocycle,
      which exhibited cation-selective and anion-controlled color change depending on
      an exo- or endo- ligand binding mode. Overall, we suggest that the exocyclic
      coordination behavior provides a versatile strategy for the preparation of new
      molecular networks and materials.

PMID- 21967329
TI  - Heparan sulfate-based treatments for regenerative medicine.
AB  - This review summarizes the emerging strategies that exploit the glycosaminoglycan
      sugar, heparan sulfate (HS), either as a substitute for, or as a supplement to
      growth factor (GF) therapy for regenerative medicine. Excluding autograft, the
      administration of GFs is currently the most effective treatment for critical bone
      repair and restoration. However, major hurdles in the clinical development of GF
      therapies include the high cost, the unwanted side effects, and the toxicity
      associated with the physiological overdosing required to achieve a successful
      outcome. These drawbacks may be overcome with the application of particular HS
      fractions that have been optimized to bind, recruit and enhance the biological
      activity of endogenous GF at the site of injury. Three HS-based treatments are
      discussed here: first, the single, localized, and sustained delivery of HS as a
      stand-alone therapeutic agent; then, the inclusion of an HS component within a
      delivery device so as to stabilize and potentiate the bioactivity of the
      incorporated GF; and finally, the growing use of HS mimetics, particularly for
      bone repair.

PMID- 21967330
TI  - Warburg effect mechanism as the target for theoretical substantiation of a new
      potential cancer treatment.
AB  - Borrowing a method from the folk healers A. Omelchenko and R. Brois for the
      treatment of oncology patients, and having evaluated the positive results of
      their treatment method, the author explains and further substantiates this method
      using the concept of the Warburg effect. In addition, the effects on an organism
      of this treatment method were explored by the author on himself, and those
      outcomes are analyzed and described. Explanations of the mechanism of the
      presented method are provided from the points of view of biochemistry, physical
      chemistry, and biophysics, and also using the concept of the Warburg effect (most
      cancer cells predominantly produce energy by a high rate of glycolysis in the
      cytosol, rather than by a comparatively low rate of glycolysis followed by
      oxidation of pyruvate in mitochondria like most normal cells). The increase in
      lactic acid production is the necessary endoergonic mechanism for accumulation of
      energy required for huge anabolic processes in glycolysis metabolism and enormous
      consumption of energy for anabolic processes in cancer tissue, i.e. lactic acids
      accumulate energy for anabolic processes in cancer tissue metabolism (see section
      II). Prolonged medical starvation (42-45 days) for treatment of oncologic
      patients was used in the presented method. Following an explanation of the
      distinctions between the Warburg effect and other medical targets for treatment
      of cancer, the author substantiates theoretically the possibility of a new method
      of cancer disease treatment. The presented method of cancer treatment is also
      described in detail. Evaluations of the mechanisms of activity of some of the
      medical targets that are used in modern methods are given, also using the Warburg
      effect mechanism. In addition, the author suggests possible modes to integrate
      the presented method of treatment for cancer with modern cancer treatment
      methods, and encourages their pursuit following detailed clinical trials.

PMID- 21967331
TI  - Notochordal cells in the adult intervertebral disc: new perspective on an old
      question.
AB  - The intervertebral disc is a tissue positioned between each of the vertebrae that
      accommodates applied biomechanical forces to the spine. The central compartment
      of the disc contains the nucleus pulposus (NP) which is enclosed by the annulus
      fibrosus and the endplate cartilage.The NP is derived from the notochord, a rod
      like structure of mesodermal origin. Development of the notochord is tightly
      regulated by interactive transcription factors and target genes. Since a number
      of these molecules are unique they have be used for cell lineage and fate mapping
      studies of tissues of the intervertebral disc. These studies have shown that in a
      number of species including human, NP tissue retains notochordal cells throughout
      life. In the adult NP, there are present both large and small notochordal cells,
      as well as a progenitor cell population which can differentiate along the
      mesengenic pathway. Since tissue renewal in the intervertebral disc is dependent
      on the ability of these cells to commit to the NP lineage and undergo terminal
      differentiation, studies have been performed to assess which signaling pathways
      may regulate these activities. The notch signaling pathway is active in the
      intervertebral disc and is responsive to hypoxia, probably through HIF-1a. From a
      disease viewpoint, it is hypothesized that an oxemic shift, possibly mediated by
      alterations in the vascular supply to the tissues of the disc would be expected
      to lead to a failure in notochordal progenitor cell activation and a decrease in
      the number of differentiated cells. In turn, this would lead to decrements in
      function and enhancement of the effect of agents that are known to promote disc
      degeneration.

PMID- 21967334
TI  - A novel biosensor based on Lactobacillus acidophilus for determination of
      phenolic compounds in milk products and wastewater.
AB  - Different branches of industry need to use phenolic compounds (PCs) in their
      production, so determination of PCs sensitively, accurately, rapidly, and
      economically is very important. For the sensitive determination of PCs, some
      biosensors based on pure polyphenol oxidase, plant tissue and microorganisms were
      developed before. But there has been no study to develop a microbial phenolic
      compounds biosensor based on Lactobacillus species, which contain polyphenol
      oxidase enzyme. In this study, we used different forms of Lactobacillus species
      as enzyme sources of biosensor and compared biosensor performances of these forms
      for determination of PCs. For this purpose, we used lyophilized Lactobacillus
      cells (containing L. bulgaricus, L. acidophilus, Streptococcus thermophilus),
      pure L. acidophilus, pure L. bulgaricus, and L. acidophilus- and L. bulgaricus
      adapted to catechol in Lactobacilli MRS Broth. The most suitable form was
      determined and optimization studies of the biosensor were carried out by using
      this form. For preparing the bioactive layer of the biosensor, the Lactobacillus
      cells were immobilized in gelatin by using glutaraldehyde. In the study, we used
      catechol as a substrate. Phenolic compound determination is based on the assay of
      the differences on the respiration activity of the cells on the oxygen meter in
      the absence and the presence of catechol. The microbial biosensor response
      depends directly on catechol concentration between 0.5 and 5.0 mM with 18 min
      response time. In the optimization studies of the microbial biosensor the most
      suitable microorganism amount was found to be 10 mg, and also phosphate buffer
      (pH 8.0; 50 mM) and 37.5  degrees C were obtained as the optimum working
      conditions. In the characterization studies of the microbial biosensor some
      parameters such as substrate specificity on the biosensor response and
      operational and storage stability were examine. Furthermore, the determination of
      PC levels in synthetic wastewater, industrial wastewater, and milk products was
      investigated by using the developed biosensor under optimum conditions.

PMID- 21967332
TI  - The role of connective tissue growth factor (CTGF/CCN2) in skeletogenesis.
AB  - Connective tissue growth factor (CTGF) is a 38 kDa, cysteine rich, extracellular
      matrix protein composed of 4 domains or modules. CTGF has been shown to regulate
      a diverse array of cellular functions and has been implicated in more complex
      biological processes such as angiogenesis, chondrogenesis, and osteogenesis. A
      role for CTGF in the development and maintenance of skeletal tissues first came
      to light in studies demonstrating its expression in cartilage and bone cells,
      which was dramatically increased during skeletal repair or regeneration. The
      physiological significance of CTGF in skeletogenesis was confirmed in CTGF-null
      mice, which exhibited multiple skeletal dysmorphisms as a result of impaired
      growth plate chondrogenesis, angiogenesis, and bone formation/mineralization.
      Given the emerging importance of CTGF in osteogenesis and chondrogenesis, this
      review will focus on its expression in skeletal tissues, its effects on
      osteoblast and chondrocyte differentiation and function, and the skeletal
      implications of ablation or over-expression of CTGF in knockout or transgenic
      mouse models, respectively. In addition, this review will examine the role of
      integrin-mediated signaling and the regulation of CTGF expression as it relates
      to skeletogenesis. We will emphasize CTGF studies in bone or bone cells, and will
      identify opportunities for future investigations concerning CTGF and
      chondrogenesis/osteogenesis.

PMID- 21967335
TI  - Expression in E. coli and purification of the fibrillogenic fusion proteins TTR
      sfGFP and beta2M-sfGFP.
AB  - The possibility of obtaining recombinant fibrillogenic fusion proteins such as
      transthyretin (TTR) and beta2-microglobulin (beta2M) with a superfolder green
      fluorescent protein (sfGFP) was studied. According to the literature data, sfGFP
      is resistant to denaturating influences, does not aggregate during renaturation,
      possesses improved kinetic characteristics of folding, and folds well when fused
      to different polypeptides. The corresponding DNA constructs for expression in
      Escherichia coli were created. It could be shown that during expression of these
      constructs in E. coli, soluble forms of the fusion proteins are synthesized.
      Efficient isolation of the fusion proteins was performed with the help of nickel
      affinity chromatography. For this purpose a polyhistidine sequence (6-His-tag)
      was incorporated into the C-terminus of the sfGFP. We could show that the
      purified fusion proteins contained full-size sequences of the most amyloidogenic
      TTR variant, TTR(L55P) and beta2M, and also sfGFP possessing fluorescent
      properties. In the course of fibrillogenesis both fusion proteins demonstrated
      their ability to form fibrils that were clearly detectable by atomic force
      microscopy. Furthermore, with the help of confocal microscopy we were able to
      reveal structures (exhibiting fluorescence) that are formed during
      fibrillogenesis. Thus, the use of sfGFP has made it possible to avoid formation
      of inclusion bodies (IB) during the synthesis of recombinant fusion proteins and
      to obtain soluble forms of TTR(L55P) and beta2M that are suitable for further
      studies.

PMID- 21967336
TI  - Hydrophobic interaction chromatography on octyl sepharose--an approach for one
      step platform purification of cyclodextrin glucanotransferases.
AB  - Cyclodextrin glucanotransferase (CGTase) from Bacillus circulans ATCC 21783 was
      concentrated by ultrafiltration and subsequently purified by hydrophobic
      interaction chromatography on Octyl Sepharose 4 fast flow. The matrix was able to
      bind selectively to the enzyme at a very low ammonium sulfate concentration of
      0.67 M and enzyme desorption was performed by decreasing gradient of the salt.
      The overall recovery was 80% with 689-fold purity. CGTases derived from four soil
      isolates and Toruzyme, the commercial preparation of CGTase, also bound to Octyl
      Sepharose under similar conditions at 0.67 M and eluted at 0.55-0.5 M of ammonium
      sulfate. Octyl Sepharose chromatography can thus be used as a platform approach
      for purification of CGTases from various bacterial sources. Long stretches of
      sequence predominated by hydrophobic amino acids are reportedly present in the
      starch binding domains of CGTases. Starch binding experiments indicated the
      binding of the enzymes to the octyl matrix through these domains.

PMID- 21967337
TI  - Production and characterization of partially purified extracellular thermostable
      alpha-amylase by Bacillus subtilis in submerged fermentation (SmF).
AB  - A Bacillus strain was isolated from soil samples from the campus area of Dicle
      University. Based on 16S ribosomal RNA sequencing, the microorganism was closely
      related to Bacillus subtilis. Effects of different culture medium, incubation
      time, carbon and nitrogen sources, and various starches, flours, and chemicals on
      alpha-amylase production were examined. Maximum enzyme production (7516 U/mL) was
      obtained in a basal medium A containing 0.05% Tween 40 in 24 h. Partially
      purified enzyme showed maximum activity at 60  degrees C with an optimum pH of
      6.0. The effects of 0.2% detergents (sodium dodecyl sulfate [SDS], CHAPS [3-[(3
      cholamidopropyl)dimethylammonio]-1-propanesulfonate], and commercial detergent
      Omo Matic) on partially purified enzyme activity over a period of time (15-150
      min) were examined and the order of inhibition effect from the most to the least
      was found as SDS > Omo Matic > CHAPS. Different metal ions inhibited alpha
      amylase activity at low concentrations (1.5 mM). Co2+ was a mild inhibitor and
      Hg2+ and Cd2+ were potent inhibitors, whereas Ca2+ and Mg2+ increased the enzyme
      activity. At 20 mM, Ca2+ enhanced enzyme activity, and different Ca2+
      concentrations (10-300 mM) were studied.

PMID- 21967333
TI  - Autophagy in tumor suppression and cancer therapy.
AB  - Autophagy is a stress-induced cell survival program whereby cells under
      metabolic, proteotoxic, or other stress remove dysfunctional organelles and/or
      misfolded/polyubiquitylated proteins by shuttling them via specialized structures
      called autophagosomes to the lysosome for degradation. The end result is the
      release of free amino acids and metabolites for use in cell survival. For tumor
      cells, autophagy is a double-edged sword: autophagy genes are frequently mono
      allelically deleted, silenced, or mutated in human tumors, resulting in an
      environment of increased oxidative stress that is conducive to DNA damage,
      genomic instability, and tumor progression. As such, autophagy is tumor
      suppressive. In contrast, it is important to note that although tumor cells have
      reduced levels of autophagy, they do not eliminate this pathway completely.
      Furthermore, the exposure of tumor cells to an environment of increased metabolic
      and other stresses renders them reliant on basal autophagy for survival.
      Therefore, autophagy inhibition is an active avenue for the identification of
      novel anti-cancer therapies. Not surprisingly, the field of autophagy and cancer
      has experienced an explosion of research in the past 10 years. This review covers
      the basic mechanisms of autophagy, discusses its role in tumor suppression and
      cancer therapy, and posits emerging questions for the future.

PMID- 21967338
TI  - Statistical media optimization for the biomass production of postharvest
      biocontrol yeast Rhodosporidium paludigenum.
AB  - A cane molasses-based medium for the biomass production of biocontrol agent
      Rhodosporidium paludigenum was statistically optimized. Molasses concentration
      (after pretreatment), yeast extract, and initial pH were identified by the
      Plackett-Burman design to show significant influence on the biomass production.
      The three factors were further optimized by central composite design and response
      surface methodology. The statistical analysis indicated the optimum values of the
      variables were 89.98 g/L for cane molasses, 2.35 g/L for yeast extract and an
      initial pH of 8.48. The biomass yield at the optimal culture achieved 15.89 g/L
      in flask fermentation, which was 2.1 times higher than that at the initial NYDB
      medium. In a 10-L fermenter, 18.97 g/L of biomass was obtained after 36 hr of
      cultivation. Moreover, the biocontrol efficacy of the yeast was investigated
      after culture optimization. The results showed the yeast harvested in the optimal
      medium maintained its initial biocontrol properties by reducing the percentage of
      decayed apples to below 20%.

PMID- 21967339
TI  - Recent developments in membrane-based separations in biotechnology processes:
      review.
AB  - Membrane-based separations are the most ubiquitous unit operations in biotech
      processes. There are several key reasons for this. First, they can be used with a
      large variety of applications including clarification, concentration, buffer
      exchange, purification, and sterilization. Second, they are available in a
      variety of formats, such as depth filtration, ultrafiltration, diafiltration,
      nanofiltration, reverse osmosis, and microfiltration. Third, they are simple to
      operate and are generally robust toward normal variations in feed material and
      operating parameters. Fourth, membrane-based separations typically require lower
      capital cost when compared to other processing options. As a result of these
      advantages, a typical biotech process has anywhere from 10 to 20 membrane-based
      separation steps. In this article we review the major developments that have
      occurred on this topic with a focus on developments in the last 5 years.

PMID- 21967341
TI  - Liver fibrosis screening for patients with psoriasis taking methotrexate: a cross
      sectional study comparing transient elastography and liver biopsy.

PMID- 21967342
TI  - Equilibration of tyrosyl radicals (Y356*, Y731*, Y730*) in the radical
      propagation pathway of the Escherichia coli class Ia ribonucleotide reductase.
AB  - Escherichia coli  ribonucleotide reductase is an alpha2beta2 complex that
      catalyzes the conversion of nucleotides to deoxynucleotides using a diferric
      tyrosyl radical (Y(122)(*)) cofactor in beta2 to initiate catalysis in alpha2.
      Each turnover requires reversible long-range proton-coupled electron transfer
      (PCET) over 35 A between the two subunits by a specific pathway (Y(122)(*) ?
      [W(48)?] ? Y(356) within beta to Y(731) ? Y(730) ? C(439) within alpha).
      Previously, we reported that a beta2 mutant with 3-nitrotyrosyl radical
      (NO(2)Y(*); 1.2 radicals/beta2) in place of Y(122)(*) in the presence of alpha2,
      CDP, and ATP catalyzes formation of 0.6 equiv of dCDP and accumulates 0.6 equiv
      of a new Y(*) proposed to be located on Y(356) in beta2. We now report three
      independent methods that establish that Y(356) is the predominant location (85
      90%) of the radical, with the remaining 10-15% delocalized onto Y(731) and Y(730)
      in alpha2. Pulsed electron-electron double-resonance spectroscopy on samples
      prepared by rapid freeze quench (RFQ) methods identified three distances: 30 +/-
      0.4 A (88% +/- 3%) and 33 +/- 0.4 and 38 +/- 0.5 A (12% +/- 3%) indicative of
      NO(2)Y(122)(*)-Y(356)(*), NO(2)Y(122)(*)-NO(2)Y(122)(*), and NO(2)Y(122)(*)
      Y(731(730))(*), respectively. Radical distribution in alpha2 was supported by RFQ
      electron paramagnetic resonance (EPR) studies using Y(731)(3,5-F(2)Y) or
      Y(730)(3,5-F(2)Y)-alpha2, which revealed F(2)Y(*), studies using globally
      incorporated [beta-(2)H(2)]Y-alpha2, and analysis using parameters obtained from
      140 GHz EPR spectroscopy. The amount of Y(*) delocalized in alpha2 from these two
      studies varied from 6% to 15%. The studies together give the first insight into
      the relative redox potentials of the three transient Y(*) radicals in the PCET
      pathway and their conformations.

PMID- 21967343
TI  - Localized temperature and chemical reaction control in nanoscale space by
      nanowire array.
AB  - We introduce a novel method for chemical reaction control with nanoscale spatial
      resolution based on localized heating by using a well-aligned nanowire array.
      Numerical and experimental analysis shows that each individual nanowire could be
      selectively and rapidly Joule heated for local and ultrafast temperature
      modulation in nanoscale space (e.g., maximum temperature gradient 2.2 K/nm at the
      nanowire edge; heating/cooling time < 2 MUs). By taking advantage of this
      capability, several nanoscale chemical reactions such as polymer
      decomposition/cross-linking and direct and localized hydrothermal synthesis of
      metal oxide nanowires were demonstrated.

PMID- 21967344
TI  - Targeting the HER2 pathway for the therapy of lower esophageal and gastric
      adenocarcinoma.
AB  - INTRODUCTION: The mysteries of complex molecular pathways of tumorigenesis are
      only beginning to be unraveled. Overexpression of HER2 receptors has been
      associated with adverse outcomes in certain malignant solid tumors. AREAS
      COVERED: The authors give a focused review of the HER2 pathway and its importance
      for cancer cell survival. Similar to the situation in breast cancer, HER2
      overexpression is seen in up to one-quarter of all gastric and gastroesophageal
      junction adenocarcinomas. The audience will also be familiarized with the
      existing HER2 targeted agents (both at the bench and at the bedside) for the
      therapy of gastric and gastroesophageal cancers. EXPERT OPINION: Despite recent
      advances, treatment of upper gastrointestinal malignancies remains a significant
      challenge. Trastuzumab in combination with chemotherapy is the current standard
      of therapy for patients with metastatic HER2-overexpressing esophageal and
      gastric cancers. The activity of lapatinib, an active agent in advanced HER2
      positive breast cancer, is now being tested in HER2-overexpressing esophageal and
      gastric adenocarcinomas. A variety of monoclonal antibodies and tyrosine kinase
      inhibitors with affinity for HER2 are in development and may improve further the
      outcomes of these malignancies.

PMID- 21967345
TI  - Comparative cost-efficiency of the EVOTECH endoscope cleaner and reprocessor
      versus manual cleaning plus automated endoscope reprocessing in a real-world
      Canadian hospital endoscopy setting.
AB  - BACKGROUND: Reprocessing of endoscopes generally requires labour-intensive manual
      cleaning followed by high-level disinfection in an automated endoscope
      reprocessor (AER). EVOTECH Endoscope Cleaner and Reprocessor (ECR) is approved
      for fully automated cleaning and disinfection whereas AERs require manual
      cleaning prior to the high-level disinfection procedure. The purpose of this
      economic evaluation was to determine the cost-efficiency of the ECR versus AER
      methods of endoscopy reprocessing in an actual practice setting. METHODS: A time
      and motion study was conducted at a Canadian hospital to collect data on the
      personnel resources and consumable supplies costs associated with the use of
      EVOTECH ECR versus manual cleaning followed by AER with Medivators DSD-201.
      Reprocessing of all endoscopes was observed and timed for both reprocessor types
      over three days. Laboratory staff members were interviewed regarding the
      consumption and cost of all disposable supplies and equipment. Exact Wilcoxon
      rank sum test was used for assessing differences in total cycle reprocessing
      time. RESULTS: Endoscope reprocessing was significantly shorter with the ECR than
      with manual cleaning followed by AER. The differences in median time were 12.46
      minutes per colonoscope (p < 0.0001), 6.31 minutes per gastroscope (p < 0.0001),
      and 5.66 minutes per bronchoscope (p = 0.0040). Almost 2 hours of direct labour
      time was saved daily with the ECR. The total per cycle cost of consumables and
      labour for maintenance was slightly higher for EVOTECH ECR versus manual cleaning
      followed by AER ($8.91 versus $8.31, respectively). Including the cost of direct
      labour time consumed in reprocessing scopes, the per cycle and annual costs of
      using the EVOTECH ECR was less than the cost of manual cleaning followed by AER
      disinfection ($11.50 versus $11.88). CONCLUSIONS: The EVOTECH ECR was more
      efficient and less costly to use for the reprocessing of endoscopes than manual
      cleaning followed by AER disinfection. Although the cost of consumable supplies
      required to reprocess endoscopes with EVOTECH ECR was slightly higher, the value
      of the labour time saved with EVOTECH ECR more than offset the additional
      consumables cost. The increased efficiency with EVOTECH ECR could lead to even
      further cost-savings by shifting endoscopy laboratory personnel responsibilities
      but further study is required.

PMID- 21967347
TI  - Status epilepticus--making progress.

PMID- 21967346
TI  - Performance and microbial diversity of palm oil mill effluent microbial fuel
      cell.
AB  - AIM: To evaluate the bioenergy generation and the microbial community structure
      from palm oil mill effluent using microbial fuel cell. METHODS AND RESULTS:
      Microbial fuel cells enriched with palm oil mill effluent (POME) were employed to
      harvest bioenergy from both artificial wastewater containing acetate and complex
      POME. The microbial fuel cell (MFC) showed maximum power density of 3004 mW m(-2)
      after continuous feeding with artificial wastewater containing acetate substrate.
      Subsequent replacement of the acetate substrate with complex substrate of POME
      recorded maximum power density of 622 mW m(-2). Based on 16S rDNA analyses,
      relatively higher abundance of Deltaproteobacteria (88.5%) was detected in the
      MFCs fed with acetate artificial wastewater as compared to POME. Meanwhile,
      members of Gammaproteobacteria, Epsilonproteobacteria and Betaproteobacteria
      codominated the microbial consortium of the MFC fed with POME with 21, 20 and
      18.5% abundances, respectively. CONCLUSIONS: Enriched electrochemically active
      bacteria originated from POME demonstrated potential to generate bioenergy from
      both acetate and complex POME substrates. Further improvements including the
      development of MFC systems that are able to utilize both fermentative and
      nonfermentative substrates in POME are needed to maximize the bioenergy
      generation. SIGNIFICANCE AND IMPACT OF THE STUDY: A better understanding of
      microbial structure is critical for bioenergy generation from POME using MFC.
      Data obtained in this study improve our understanding of microbial community
      structure in conversion of POME to electricity.

PMID- 21967348
TI  - Ontogenetic modifications of neuronal excitability during brain maturation:
      developmental changes of neurotransmitter receptors.
AB  - The development of the human brain depends on a precisely orchestrated cascade of
      events, including proliferation, migration and maturation of neural progenitor
      cells. Different mechanisms coordinate these stages to reach a normal structural
      organization, producing appropriate excitatory and inhibitory networks. Here, we
      will briefly review the developmental changes of glutamate (Glu) and gamma
      aminobutyric acid (GABA) receptors, with particular attention to the development
      of the human brain. We will also briefly discuss recent evidence on the
      involvement of the endocannabinoid signaling in the regulation of neuronal
      excitability during early brain development..

PMID- 21967349
TI  - Mitochondrial function and pathology in status epilepticus.
AB  - The mitochondrial respiratory chain is the final common pathway for energy
      production. Defects affecting this pathway can give rise to disease that presents
      at any age and affects any tissue. However, irrespective of genetic defect,
      epilepsy is common and there is a significant risk of status epilepticus. We have
      studied two types of mitochondrial disease: one arising from a defect in
      mitochondrial DNA (mtDNA) (MELAS) and one due to a nuclear gene mutation (POLG).
      These two disorders show similarities in their clinicopathologic evolution and in
      findings in postmortem samples. Our findings based on antemortem magnetic
      resonance imaging (MRI) and postmortem studies suggest that the status
      epilepticus that is seen in both appears to be the result of cortical damage
      resulting from a common mechanism, namely energy failure.

PMID- 21967350
TI  - Potentially pathogenic autoantibodies associated with epilepsy and encephalitis
      in children and adults.
AB  - Autoantibodies to surface proteins that influence neuronal excitability are
      increasingly found in different forms of epilepsy or encephalitis in adults, and
      are also beginning to be identified in children. The conditions are often
      refractory to traditional antiepileptic drugs. Detection of these antibodies can
      help to identify forms of epilepsy that may respond to immunotherapies.

PMID- 21967351
TI  - Computational modeling of epilepsy.
AB  - With the rapid rise in our knowledge about the structural and functional
      properties of neuronal microcircuits and the exponentially increasing power of
      computers, it has become possible to closely integrate experimental findings with
      large-scale, anatomically and biophysically realistic computational simulations
      of control and epileptic neuronal networks with unprecedented precision and
      predictive power. In this paper, we discuss the biological basis of model
      development, and outline specific applications, including exciting new
      computational and experimental results concerning the roles of aberrant
      hyperconnected hub-like neurons in seizures.

PMID- 21967352
TI  - Light-activated channels in acute seizures.
AB  - Optogenetics allow for timely precise and cell-population specific activation or
      inhibition of neuronal activity. Hallorhodopsin NpHR is an inward cholride pump,
      which when activated by orange light, hyperpolarises neuronal membrane and
      inhibitis action potential generation. We were first to show that transduction of
      principal neurons with NpHR in organotypic hippocampal slice cultures effectivey
      attenuates epileptiform activity when exposed to orange light. Our data suggest
      that optogenetic approach may become a useful method for controlling epileptiform
      activity, and may open novel avenues to develop alternative treatment strategies
      for epilepsy.

PMID- 21967353
TI  - Blood-brain barrier dysfunction, status epilepticus, seizures, and epilepsy: a
      puzzle of a chicken and egg?
AB  - Status epilepticus is often associated with endothelial dysfunction and increased
      vessels permeability. We discuss here the direct role of blood-brain barrier
      (BBB) dysfunction in epileptogenesis and brain damage. On the cellular level,
      astrocytes respond early to the efflux of serum proteins in the presence of
      dysfunctional BBB, with activation of the innate immune system and disturbed
      homeostasis of extracellular potassium and glutamate. In turn, there is enhanced
      excitability of neurons and altered network connectivity. Transforming growth
      factor beta (TGF-beta) signaling appears to be a potential new target for the
      prevention of epileptogenesis and secondary damage following status epilepticus.

PMID- 21967354
TI  - Classification of EEG patterns in patients with impaired consciousness.
AB  - There is significant variability and controversy regarding the interpretation,
      nomenclature, and clinical implications of many EEG patterns seen in
      encephalopathic patients. The American Clinical Neurophysiology Society has
      attempted to create well-defined, objective rules for naming these patterns in
      order to allow scientific investigation into their significance. After many
      revisions, clarifications in definitions, and Web-based training modules,
      interrater reliability has improved. A perfect system for describing complex wave
      forms with words will never be perfect; scalp EEG itself has substantial
      limitations, as intracranial recordings in neurocritical care patients have
      shown. The latest version of the nomenclature is available at
      http://www.acns.org.

PMID- 21967355
TI  - Cellular mechanisms underlying EEG waveforms during coma.
AB  - This paper describes the various electroencephalographic (EEG) patterns expressed
      by the comatose brain, starting with the sleep-like oscillations associated with
      light coma. Deeper coma generally displays a burst-suppression pattern
      characterized by alternating episodes of isoelectric (flat) EEG and bursting slow
      waves. The latter are the result of cortical hyperexcitability, as demonstrated
      by intracellular recordings in anesthetized animals. Further deepening of the
      coma yields to continuous isoelectric EEG and eventually results in a newly
      discovered type of spiky waves that have been termed nu-complexes. They originate
      in the hippocampus as a result of intrinsically generated oscillations (ripples)
      in the delta range.

PMID- 21967356
TI  - Febrile infection-related epilepsy syndrome (FIRES): does duration of anesthesia
      affect outcome?
AB  - We conducted a retrospective multicenter study on children who had been included
      in eight studies published between November 2001 and July 2010 to explore the
      correlations between burst-suppression coma (BSC) with outcome in febrile
      infection-related epilepsy syndrome (FIRES). The 77 enrolled patients presented
      with prolonged refractory status epilepticus. BSC was induced in 46 patients.
      Cognitive levels at follow-up were significantly associated with duration of a
      BSC (p=0.005). The outcome of FIRES is poor. Treatment by inducing a prolonged
      BSC was associated with a worse cognitive outcome.

PMID- 21967357
TI  - Canine status epilepticus: a translational platform for human therapeutic trials.
AB  - Current treatment of human status epilepticus (SE) relies on drugs developed for
      chronic treatment of epilepsy. Many potent compounds have been discovered in
      animal models of SE. But they may never be useful for chronic treatment of
      epilepsy and thus not available for human use. Naturally occurring canine SE may
      become a translational platform for evaluating these compounds for eventual use
      in human trials. A pilot study of levetiracetam in canine SE demonstrated a 56%
      response rate compared to 10% for placebo. Based on these results we have
      obtained an NIH R-21 to further evaluate canine SE as a translational platform
      for developing new approaches for treating human SE.

PMID- 21967358
TI  - What is the evidence to use new intravenous AEDs in status epilepticus?
AB  - Current standard treatment of established status epilepticus after failure of
      benzodiazepines is intravenous phenytoin/fosphenytoin, phenobarbital, or
      valproate. Since 2006 two new antiseizure drugs have become available as
      intravenous formulation: levetiracetam (2006) and lacosamide (2008). Both drugs
      have been taken up very rapidly by the clinicians to treat acute seizures and
      status epilepticus, despite lack of evidence from randomized controlled trials.
      The favorable pharmacokinetic profile and the good tolerability, especially the
      lack of sedating effects of both drugs make them promising potential alternatives
      to the standard antiseizure drugs. Future randomized controlled trials are needed
      to inform clinicians better about the best choice of treatment in established
      status epilepticus. The experimental evidence as well as the current clinical
      experience with levetiracetam and lacosamide are summarized in this review.

PMID- 21967359
TI  - Complications of the management of status epilepticus in the intensive care unit.
AB  - Barbiturates and propofol are widely used to control status epilepticus. This
      review aims to discuss all possible adverse effects incurred by the
      administration of GABA-mediated anesthetic agents. Further on unconventional
      therapies such as ketamine, lidocaine, or anesthetic agents are discussed both
      with respect to efficacy and complications. The aim of this review is to raise
      awareness of complications incurred by therapeutic approaches to patients with
      status epilepticus in the intensive care unit.

PMID- 21967360
TI  - Anesthestic agents and status epilepticus.
AB  - There is little evidence to guide the choice of intravenous anesthetic agent to
      treat refractory status epilepticus but midazolam, propofol, and barbiturates are
      widely used. It is impractical to use inhalational anesthetic agents in most
      circumstances and there is little experience with non-GABA-ergic agents such as
      ketamine. A more aggressive treatment approach, aiming for EEG suppression, is
      most likely to result in sustained cessation of seizure activity but this is
      associated with increased treatment-related complications. Side effects of
      treatment, including hypotension, gastric paresis, and pneumonia, are common and
      contribute independently to poor outcome and death.

PMID- 21967361
TI  - RAMPART (Rapid Anticonvulsant Medication Prior to Arrival Trial): a double-blind
      randomized clinical trial of the efficacy of intramuscular midazolam versus
      intravenous lorazepam in the prehospital treatment of status epilepticus by
      paramedics.
AB  - Early treatment of prolonged seizures with benzodiazepines given intravenously by
      paramedics in the prehospital setting has been shown to be associated with
      improved outcomes. However, an increasing number of Emergency Medical System
      (EMS) protocols use an intramuscular (IM) route because it is faster and
      consistently achievable. RAMPART (Rapid Anticonvulsant Medication Prior to
      Arrival Trial) is a double-blind randomized clinical trial to determine if the
      efficacy of IM midazolam is noninferior by a margin of 10% to that of intravenous
      (IV) lorazepam in patients treated by paramedics for status epilepticus (SE).
      Children and adults with >5 min of convulsions who are still seizing after
      paramedic arrival are administered study medication by IM autoinjector or IV
      infusion. The primary efficacy outcome is absence of seizures at emergency
      department (ED) arrival, without EMS rescue therapy. Safety outcomes include
      acute endotracheal intubation and recurrent seizures. Secondary outcomes include
      timing of treatment and initial seizure cessation. At the time of writing this
      communication, enrollment of all subjects is near completion and the study data
      will soon be analyzed.

PMID- 21967362
TI  - A prehospital randomized trial in convulsive status epilepticus.
AB  - Therapeutic strategies for patients with generalized convulsive status
      epilepticus (GCSE) need to be improved. We present the design of an add-on,
      randomized, double-blind, placebo-controlled, phase III clinical trial, to
      compare the efficacy for GCSE of intravenous levetiracetam in association with
      clonazepam versus clonazepam alone. In the therapeutic arm, 1 mg clonazepam is
      injected together with 2500 mg levetiracetam over 5 min. In the control arm, 1 mg
      clonazepam is injected together with a placebo over 5 min. This ongoing study is
      managed by prehospital physicians within emergency mobile units (SAMU). Adult
      patients with GCSE lasting more than 5 minutes are included in the study. The
      primary outcome measure is the percentage of patients with cessation of
      convulsions within 15 minutes of the onset of initial injections. Emergency
      medical consent is obtained from family members. An informed consent for
      continued participation is also obtained from patients when they wake. The study
      is currently recruiting participants.

PMID- 21967363
TI  - Established status epilepticus treatment trial (ESETT).
AB  - Phenytoin (PHT) has been the standard treatment for convulsive status epilepticus
      (SE) where initial benzodiazepines have failed for many years, despite that it
      has many limitations in the emergency situation. Valproate (VPA) and
      levetiracetam (LEV) are emerging as potentially superior alternatives, and there
      is an urgent need for an adequately powered comparative randomized controlled
      trial (RCT). An international group, having not succeeded in obtaining funding
      from the United Kingdom in 2010, is now preparing a revised proposal for
      submission to the National Institute of Neurological Disorders and Stroke (NINDS)
      to undertake a blinded comparative RCT using an adaptive design. This will be
      necessarily international and multicenter, requiring up to 1,500 patients from
      over 50 centers, and if successful will commence recruiting in 2012. The primary
      outcome, agreed from the 2009 SE workshop as pragmatic, generalizable, and
      clinically meaningful, will be cessation of seizures without need for other drug
      or sedation, and without serious adverse events, maintained for at least 2 h.

PMID- 21967364
TI  - Super-refractory status epilepticus: an approach to therapy in this difficult
      clinical situation.
AB  - Super-refractory status epilepticus (SE) is a stage of refractory SE
      characterized by unresponsiveness to initial anesthetic therapy. It is a new
      concept that has been the focus of recent basic and therapeutic work, and is
      defined as "SE that continues or recurs 24 hours or more after the onset of
      anesthesia, including those cases in which SE recurs on the reduction or
      withdrawl of anesthesia." It is encountered typically, but not exclusively, in
      two quite distinctive clinical situations: (1) in patients with severe acute
      brain injury, and (2) in patients with no history of epilepsy in whom status
      epilepticus develops out of the blue with no overt cause. There are a variety of
      treatments used, almost entirely based on open observational studies or case
      reports. Therapy includes anesthesia, antiepileptic drug therapy, hypothermia and
      ICU therapy, other medical, immunological, and physical therapies. In this
      review, the range of possible therapies is outlined and an approach to therapy is
      discussed.

PMID- 21967365
TI  - Multimodal MRI assessment of damage and plasticity caused by status epilepticus
      in the rat brain.
AB  - Status epilepticus or other brain-damaging insults launch a cascade of events
      that may lead to the development of epilepsy. MRI techniques available today,
      including T(2) - and T(1) -weighted imaging, functional MRI, manganese enhanced
      MRI (MEMRI), arterial spin labeling (ASL), diffusion tensor imaging (DTI), and
      phase imaging, can detect not only damage caused by status epilepticus but also
      plastic changes in the brain that occur in response to damage. Optimal balance
      between damage and recovery processes is a key for planning possible treatments,
      and noninvasive imaging has the potential to greatly facilitate this process and
      to make personalized treatment plans possible.

PMID- 21967366
TI  - The potential of brain stimulation in status epilepticus.
AB  - There is a long history of the use of brain stimulation in the treatment of
      epilepsy but relatively little experience for its use in status epilepticus.
      Electroconvulsive therapy, transcranial magnetic stimulation, subcortical and
      cortical stimulation have all been tried with varying degrees of success in
      single cases or small case series. It remains unclear, however, which brain areas
      should be stimulated and the parameters that should be used. Moreover, the aim
      (stopping status epilepticus) is different from preventing seizures and so the
      brain areas and parameters that are useful in epilepsy may not directly translate
      to the treatment of status epilepticus.

PMID- 21967367
TI  - What is the value of hypothermia in acute neurologic diseases and status
      epilepticus?
AB  - Patients with status epilepticus that proves refractory to anesthetic agents
      represent a daunting challenge for treating clinicians. Animal data support the
      neuroprotective action of brain hypothermia, and its efficacy in status
      epilepticus models. This approach, targeting a core temperature of about 33
      degrees C for at least 24 hours together with pharmacological sedation, has been
      described in adults and children. However, although relatively safe if
      concomitant barbiturates are avoided, it seems that mild hypothermia rarely
      allows a sustained control of ongoing status epilepticus, since seizures tend to
      recur in normothermia. Conversely, mild hypothermia has a high-evidence level and
      is increasingly used in postanoxic encephalopathy, both in newborns and adults.
      Due to the paucity of available clinical data, prospective studies are needed to
      assess the value of hypothermia in status epilepticus.

PMID- 21967368
TI  - Therapeutic potential of new antiinflammatory drugs.
AB  - Experimental and clinical findings have shown in the past decade that specific
      proinflammatory mediators and their cognate receptors are upregulated in
      epileptic brain tissue. In particular, the IL-1 receptor (R)/Toll-like receptor
      (TLR) signaling pathways are activated in experimental models of seizures and in
      human epileptic tissue from drug-resistant patients. Pharmacological targeting of
      these proinflammatory pathways using selective receptor antagonists, or the use
      of transgenic mice with perturbed cell signaling, demostrated that the activation
      of IL-1R type 1 and TLR4 by their respective endogenous ligands, i.e.,
      interleukin (IL)-1b and High Mobility Group Box 1, is implicated in the
      precipitation and recurrence of experimentally induced seizures in rodents. This
      evidence highlights a new target system for pharmacological intervention to
      inhibit seizures by interfering with mechanisms involved in their genesis and
      recurrence.

PMID- 21967369
TI  - Rational polytherapy in the treatment of acute seizures and status epilepticus.
AB  - We used a model of severe cholinergic status epilepticus (SE) to study
      polytherapy aimed at reversing the effects of seizure-induced loss of synaptic
      GABA(A)  receptors and seizure-induced gain of synaptic NMDA receptors.
      Combinations of a benzodiazepine with ketamine and valproate, or with ketamine
      and brivaracetam, were more effective and less toxic than benzodiazepine
      monotherapy in this model of SE.

PMID- 21967371
TI  - Consumer perspectives on the usability and value of the iBOT((r)) wheelchair:
      findings from a case series.
AB  - PURPOSE: The iBOT((r)) is an advanced power wheelchair introduced in 2003 for
      people with mobility impairments to enhance their independence and community
      access. Although this innovation soon gained popularity, the production of this
      wheelchair was recently stopped owing to the lower-than-expected sale figures. In
      this scenario, this study examines the impact of this wheelchair on current
      consumers by highlighting its usability in multiple contexts and verifying the
      value associated with its ownership. METHOD: Seven active consumers of the
      iBOT((r)) were interviewed using a mixed method approach. Participants discussed
      and rated the iBOT's usability in relation to their standard power wheelchair and
      shared their perceived value for it. A content analysis was used to elucidate the
      qualitative data, whereas the quantitative data was analyzed using descriptive
      and non-parametric comparisons to compute differences in consumer ratings for the
      two wheelchairs. RESULT: Results, although statistically non-significant (alpha <
      0.05), indicated the iBOT((r)) to be a highly multi-functional wheelchair with
      relatively superior usability in workplace (p = 0.15), community (p = 0.18) and
      outdoors (p = 0.1). Participants greatly valued its capability to expand their
      mobility in otherwise inaccessible environments and to enhance their social
      participation through eye level communication. CONCLUSION: The iBOT((r)) serves
      as an exemplar to promote interest and funding for advanced AT devices for people
      with disabilities. [Box: see text].

PMID- 21967373
TI  - Capacity of visual classical conditioning in Drosophila larvae.
AB  - Vision is an ancient sense essential for various aspects of animal behavior.
      Visual information not only leads to immediate, temporary, and rapid behavioral
      responses but also has lasting effects. Naive behavioral responses to light are
      not always identical but can be altered based on positive or negative experience
      a process defined as visual learning. In this study, Drosophila larvae were used
      as a simple model to study visual classical conditioning. We show that larvae are
      able to associate positive or negative cues with either light or darkness, thus
      changing their native light-preference. This effect can be robustly provoked
      through gustatory stimuli and electric shock. We further show that light can not
      only be used as a conditioned stimulus but also as an unconditioned stimulus, as
      punishment in the olfactory classical conditioning procedure, possibly forming
      two different kinds of memories. Our findings show that even though larvae show a
      strong naive response when exposed to light, the animals display a comparably
      large repertoire of visual memories that can be formed. Therefore, our study
      provides an impacting entry point into the genetic dissection of the neuronal
      circuit that underlies different types of visual learning.

PMID- 21967372
TI  - A rhesus macaque model of Streptococcus pneumoniae carriage.
AB  - BACKGROUND: Nasopharyngeal colonization by Streptococcus pneumoniae precedes
      pneumococcal disease. Elucidation of procedures to prevent or eradicate
      nasopharyngeal carriage in a model akin to the human would help to diminish the
      incidence of both pneumonia and invasive pneumococcal disease. METHODS: We
      conducted a survey of the nasopharynx of infant rhesus macaques from our breeding
      colony, in search of natural carriers of S. pneumoniae. We also attempted
      experimental induction of colonization, by nasopharyngeal instillation of a human
      S. pneumoniae strain (19F). RESULTS: None of 158 colony animals surveyed carried
      S. pneumoniae in the nasopharynx. Colonization was induced in eight of eight
      infant rhesus by nasopharyngeal instillation and lasted 2weeks in 100% of the
      animals and 7weeks in more than 60%. CONCLUSION: Rhesus macaques are probably not
      natural carriers of S. pneumoniae. The high rate and duration of colonization
      obtained in our experiments indicates that the rhesus macaque will serve as a
      human-like carriage model.

PMID- 21967374
TI  - Endocrine substrates of cognitive and affective changes during pregnancy and
      postpartum.
AB  - Pregnancy and motherhood constitute periods of tremendous hormonal variation that
      orchestrate parturition, lactation, maternal care, maternal aggression, and
      recognition of offspring, among other functions. Cognitive processing also varies
      during pregnancy and motherhood and may serve an adaptive function in preparation
      for parturition and rearing. Additionally, maternal experience may have enduring
      consequences for the brain, behavior, and cognition long after offspring are
      mature. However, the early postpartum period also renders women psychologically
      vulnerable as approximately 15% of women experience postpartum depression, with
      estimates of 50-80% reporting a milder form of depression termed "maternal
      blues." This review will present literature on pregnancy- and parity-related
      changes in both cognition and affect and how these changes likely involve plastic
      changes within the hippocampus, a region that is sensitive to reproductive
      hormones. Further, this review will discuss steroid and peptide hormones that may
      contribute to affective and cognitive disruptions during pregnancy and
      postpartum. Research in this area may reveal insight into how pregnancy and
      motherhood alter the likelihood of developing postpartum depression and related
      disorders.

PMID- 21967376
TI  - Introduction to special section: Environmental health for rural populations.

PMID- 21967377
TI  - Environmental carcinogen releases and lung cancer mortality in rural-urban areas
      of the United States.
AB  - PURPOSE: Environmental hazards are unevenly distributed across communities and
      populations; however, little is known about the distribution of environmental
      carcinogenic pollutants and lung cancer risk across populations defined by race,
      sex, and rural-urban setting. METHODS: We used the Toxics Release Inventory (TRI)
      database to conduct an ecological study at the county level (a total of 3,141
      counties). Multiple linear regressions were used to assess the associations of
      carcinogenic discharges from TRI sites and lung cancer mortality rates at the
      county level in the United States during the years 1990 through 2007. FINDINGS:
      We observed an excess risk of population lung cancer mortality associated with
      higher amounts of environmental carcinogen releases from TRI facilities in both
      males and females, and in both whites and African Americans. The strength of
      these associations tended to be stronger in African Americans. A significant dose
      response relationship was observed for the total volume of carcinogen releases or
      carcinogen releases to the air, but not releases to water. These associations
      appeared to be present within nonmetropolitan counties but not metropolitan
      counties, and to be concentrated in certain urban-rural county typologies.
      CONCLUSIONS: Our results suggest that exposure to higher carcinogen releases from
      industrial or chemical facilities in rural areas may increase the risk of lung
      cancer mortality. Our findings add to the evidence for undertaking prudent
      efforts to limit the release of carcinogenic chemicals into the environment.

PMID- 21967378
TI  - Chronic cardiovascular disease mortality in mountaintop mining areas of central
      Appalachian states.
AB  - PURPOSE: To determine if chronic cardiovascular disease (CVD) mortality rates are
      higher among residents of mountaintop mining (MTM) areas compared to mining and
      nonmining areas, and to examine the association between greater levels of MTM
      surface mining and CVD mortality. METHODS: Age-adjusted chronic CVD mortality
      rates from 1999 to 2006 for counties in 4 Appalachian states where MTM occurs (N
      = 404) were linked with county coal mining data. Three groups of counties were
      compared: MTM, coal mining but not MTM, and nonmining. Covariates included
      smoking rate, rural-urban status, percent male population, primary care physician
      supply, obesity rate, diabetes rate, poverty rate, race/ethnicity rates, high
      school and college education rates, and Appalachian county. Linear regression
      analyses examined the association of mortality rates with mining in MTM areas and
      non-MTM areas and the association of mortality with quantity of surface coal
      mined in MTM areas. FINDINGS: Prior to covariate adjustment, chronic CVD
      mortality rates were significantly higher in both mining areas compared to
      nonmining areas and significantly highest in MTM areas. After adjustment,
      mortality rates in MTM areas remained significantly higher and increased as a
      function of greater levels of surface mining. Higher obesity and poverty rates
      and lower college education rates also significantly predicted CVD mortality
      overall and in rural counties. CONCLUSIONS: MTM activity is significantly
      associated with elevated chronic CVD mortality rates. Future research is
      necessary to examine the socioeconomic and environmental impacts of MTM on health
      to reduce health disparities in rural coal mining areas.

PMID- 21967379
TI  - The relationship between toxics release inventory discharges and mortality rates
      in rural and urban areas of the United States.
AB  - BACKGROUND: Potential environmental exposures from chemical manufacturing or
      industrial sites have not been well studied for rural populations. The current
      study examines whether chemical releases from facilities monitored through the
      Toxics Release Inventory (TRI) program are associated with population mortality
      rates for both rural and urban populations. METHODS: We used the TRI database,
      Centers for Disease Control and Prevention age-adjusted mortality data, and
      additional county-level covariate data to conduct a national study at (N = 3,142)
      of the association between amounts of on-site TRI air and water releases for the
      years 1988-2006 and total age-adjusted mortality rates for the years 1999-2006,
      after controlling for the effects of other risk variables. RESULTS: Results of
      multiple linear regression analyses indicated significantly higher adjusted
      mortality rates associated with greater water and air releases in both rural and
      urban counties. The strongest associations between TRI releases and rural
      mortality rates were found when 8 or more prior years of TRI release data were
      used to study subsequent mortality. CONCLUSION: The results support the use of
      the TRI as a public reporting tool and a research tool, and demonstrate that
      greater amounts of air and water TRI releases are related to mortality outcomes
      for both rural and urban populations.

PMID- 21967380
TI  - A national study of the association between food environments and county-level
      health outcomes.
AB  - PURPOSE: This national, county-level study examines the relationship between food
      availability and access, and health outcomes (mortality, diabetes, and obesity
      rates) in both metro and non-metro areas. METHODS: This is a secondary, cross
      sectional analysis using Food Environment Atlas and CDC data. Linear regression
      models estimate relationships between food availability and access variables
      (direct-to-consumer farm sales, per capita grocery stores, full-service
      restaurants, fast food restaurants, and convenience stores) with health outcomes.
      Controls include smoking, race/ethnicity, gender, age, education, poverty,
      primary care availability, recreational facility availability, and
      mobility/distance-from-grocery-store. FINDINGS: Non-metro findings: Lower
      adjusted mortality rates were associated with more per capita full-service
      restaurants and grocery stores, and greater per capita direct farm sales. Lower
      adjusted diabetes rates were associated with a lower per capita supply of fast
      food restaurants and convenience stores, and more per capita full-service
      restaurants and grocery stores. Lower adjusted obesity rates were associated with
      more per capita full-service restaurants and grocery stores. Unexpectedly,
      obesity rates were positively associated with per capita grocery stores and
      negatively associated with fast food restaurants. Metro findings: More per capita
      full-service restaurants, grocery stores, and direct farm sales are associated
      with positive health outcomes; fast food restaurants and convenience stores are
      associated with negative health outcomes. CONCLUSIONS: The food
      access/availability environment is an important determinant of health outcomes in
      metro and non-metro areas. Future research should focus on more refined
      specifications that capture variability across non-metro settings.

PMID- 21967381
TI  - Uptake of free HPV vaccination among young women: a comparison of rural versus
      urban rates.
AB  - PURPOSE: To contrast rates of initial HPV vaccine uptake, offered at no cost,
      between a rural clinic, a rural community college, and an urban college clinic
      and to identify rural versus urban differences in uptake of free booster doses.
      METHODS: Young rural women attending rural clinics (n = 246), young women
      attending a rural community college (n = 251) and young women attending an urban
      university health clinic (n = 209) were recruited in Kentucky. After completing a
      brief questionnaire, women received a free voucher for HPV vaccination. Whether
      women redeemed the voucher for the initial dose of vaccine served as the study
      outcome variable. FINDINGS: In controlled analyses, the contrast in initial
      uptake between urban clinic women (reference category) and rural college women
      was significant (P < .0001). However, the contrast in initial uptake between
      urban clinic women (reference category) and rural clinic women was not
      significant (P = .42). The model predicting uptake of subsequent doses among
      those with initial uptake (n = 235) also indicated significant differences as a
      function of recruitment location, with rural clinic women being about 7 times
      more likely than urban clinic women (P < .0001) to not return for at least 1
      follow-up dose. The contrast between urban clinic women and rural college women
      was also significant (P = .014). CONCLUSION: Initial uptake of free HPV
      vaccination among young rural college women may be problematic. Moreover, uptake
      of subsequent free doses among rural women may be problematic regardless of
      whether contact is made in a clinic or through college recruitment.

PMID- 21967382
TI  - To give or not to give: Approaches to early childhood immunization delivery in
      Oregon rural primary care practices.
AB  - CONTEXT: Little is known about rural clinicians' perspectives regarding early
      childhood immunization delivery, their adherence to recommended best immunization
      practices, or the specific barriers they confront. PURPOSE: To examine
      immunization practices, beliefs, and barriers among rural primary care clinicians
      for children in Oregon and compare those who deliver all recommended
      immunizations in their practices with those who do not. METHODS: A mailed
      questionnaire was sent to all physicians, nurse practitioners, and physician
      assistants practicing primary care in rural communities throughout Oregon.
      FINDINGS: While 39% of rural clinicians reported delivering all childhood
      immunizations in their clinic, 43% of clinicians reported that they refer
      patients elsewhere for some vaccinations, and 18% provided no immunizations in
      the clinic whatsoever. Leading reasons for referral include inadequate
      reimbursement, parental request, and storage and stocking difficulties. Nearly a
      third of respondents reported that they had some level of concern about the
      safety of immunizations, and 14% reported that concerns about safety were a
      specific reason for referring. Clinicians who delivered only some of the
      recommended immunizations were less likely than nonreferring clinicians to have
      adopted evidence-based best immunization practices. CONCLUSIONS: This study of
      rural clinicians in Oregon demonstrates the prevalence of barriers to primary
      care based immunization delivery in rural regions. While some barriers may be
      difficult to overcome, others may be amenable to educational outreach and
      support. Thus, efforts to improve population immunization rates should focus on
      promoting immunization "best practices" and enhancing the capacity of practices
      to provide immunizations and ensuring that any alternative means of delivering
      immunizations are effective.

PMID- 21967383
TI  - In-hospital mortality among rural Medicare patients with acute myocardial
      infarction: the influence of demographics, transfer, and health factors.
AB  - CONTEXT/PURPOSE: Most rural hospitals can provide medical care to acute
      myocardial infarction (AMI) patients, but a need for advanced cardiac care
      requires timely transfer to a tertiary hospital. There is little information on
      AMI in-hospital mortality predictors among rural transfer patients. METHODS:
      Cross-sectional retrospective analyses on 2003-2005 Medicare hospital inpatient
      data from 5 states were conducted to compare predictors of in-hospital AMI
      mortality between rural hospital transferred and nontransferred patients. A total
      of 9,690 rural hospital AMI patients were identified: 3,087 were transferred to
      receiving hospitals and 6,603 were not transferred. Separate logistic regressions
      were conducted for transferred and nontransferred patient cohorts and results
      were compared. RESULTS: Transfer patients were younger, more likely male, had
      fewer comorbidities/complications, and were less likely to expire (5.3% vs 16.7%)
      in the hospital. Congestive heart failure and cardiac dysrhythmia were the most
      common comorbidities/complications among transfer and no-transfer AMI patients,
      but shock (OR = 9.44) and acute renal failure (OR = 3.67) had the strongest
      associations with in-hospital mortality for both cohorts. Undergoing a
      percutaneous coronary intervention (PCI) was associated with a 42% reduction in
      hospital mortality risk for transfer patients. CONCLUSIONS: Transfer was
      associated with a greater likelihood of in-hospital AMI survival, largely but not
      fully explained by transfer patients being younger with fewer
      comorbidities/complications who are receiving advanced cardiac care. Additional
      studies are needed to clarify other factors that explain higher in-hospital
      mortality among nontransfers, such as patients' health care decision-making.

PMID- 21967384
TI  - Similar secondary stroke prevention and medication persistence rates among rural
      and urban patients.
AB  - PURPOSE: Rural residents are less likely to obtain optimal care for many serious
      conditions and have poorer health outcomes than those residing in more urban
      areas. We determined whether rural vs urban residence affected postdischarge
      medication persistence and 1 year outcomes after stroke. METHODS: The Adherence
      eValuation After Ischemic Stroke-Longitudinal (AVAIL) study is a multicenter
      registry of stroke patients enrolled in 101 hospitals nationwide. Medications
      were recorded at hospital discharge and again after 3 and 12 months. Persistence
      was defined as continuation of prescribed discharge medications. Participants
      were categorized as living in rural or urban settings by cross-referencing home
      ZIP code with metropolitan statistical area (MSA) designation. FINDINGS: Rural
      patients were younger, more likely to be white, married, smokers, and less likely
      to be college graduates. There was no difference in stroke type or working status
      compared to urban patients, and there were minor differences in comorbid
      conditions. There were no differences based on rural vs urban residence in
      medication persistence at 3 or 12 months postdischarge and no differences in
      outcomes of recurrent stroke or rehospitalization at 12 months. CONCLUSION:
      Despite differences in patient characteristics, there was no difference in
      medication persistence or outcomes between rural and urban dwellers after
      hospitalization for ischemic stroke or transient ischemic attack (TIA).

PMID- 21967386
TI  - Partnering with communities to address the mental health needs of rural veterans.
AB  - PURPOSE: Many veterans who face mental illness and live in rural areas never
      obtain the mental health care they need. To address these needs, it is important
      to reach out to community stakeholders who are likely to have frequent
      interactions with veterans, particularly those returning from Operations Enduring
      and Iraqi Freedom (OEF/OIF). METHODS: Three community stakeholder groups-clergy,
      postsecondary educators, and criminal justice personnel-are of particular
      importance for OEF/OIF veterans living in rural areas and may be more likely to
      come into contact with rural veterans struggling with mental illness or substance
      abuse than the formal health care system. This article briefly describes the
      conceptualization, development, initial implementation, and early evaluation of a
      Veterans Affairs (VA) medical center-based program designed to improve engagement
      in, and access to, mental health care for veterans returning to rural areas.
      FINDINGS: One year since initial funding, 90 stakeholders have attended formal
      training workshops (criminal justice personnel = 36; educators = 31; clergy =
      23). Two training formats (a 2-hour workshop and an intensive 2.5-day workshop)
      have been developed and provided to clergy in 1 rural county with another county
      scheduled for training. A veteran outreach initiative, which has received 32
      referrals for various student services, has been established on 4 rural college
      campuses. A Veterans Treatment Court also has been established with 16 referrals
      for eligibility assessments. CONCLUSIONS: While this pilot program is in the
      early stages of evaluation, its success to date has encouraged program and VA
      clinical leadership to expand beyond the original sites.

PMID- 21967385
TI  - Rural adolescent alcohol, tobacco, and illicit drug use: a comparison of students
      in Victoria, Australia, and Washington State, United States.
AB  - PURPOSE: There are inconsistent research findings regarding the impact of
      rurality on adolescent alcohol, tobacco, and illicit substance use. Therefore,
      the current study reports on the effect of rurality on alcohol, tobacco, and
      illicit drug use among adolescents in 2 state representative samples in 2
      countries, Washington State (WA) in the United States and Victoria (VIC) in
      Australia. PARTICIPANTS: The International Youth Development Study (IYDS)
      recruited representative samples of students from Grade 7 (aged 12 to 13 years)
      and Grade 9 (aged 14 to 15) in both states. A total of 3,729 students responded
      to questions about alcohol, tobacco, cannabis, and other illicit substance use
      (n(VIC) = 1,852; n(WA) = 1,877). In each state, males and females were equally
      represented and ages ranged from 12 to 15 years. METHODS: Data were analyzed to
      compare lifetime and current (past 30 days) substance use for students located in
      census areas classified as urban, large or small town, and rural. Findings were
      adjusted for school clustering and weighted to compare prevalence at median age
      14 years. FINDINGS: Rates of lifetime and current alcohol, tobacco, and cannabis
      use were significantly higher in rural compared to urban students in both states
      (odds ratio for current substance use = 1.31). CONCLUSIONS: In both Washington
      State and Victoria, early adolescent rural students use substances more
      frequently than their urban counterparts. Future studies should examine factors
      that place rural adolescents at risk for alcohol, tobacco, and illicit drug use.

PMID- 21967387
TI  - VA community mental health service providers' utilization of and attitudes toward
      telemental health care: the gatekeeper's perspective.
AB  - CONTEXT: Mental health (MH) providers in community-based outpatient clinics
      (CBOCs) are important stakeholders in the development of the Veterans Health
      Administration (VA) telemental health (TMH) system, but their perceptions of
      these technologies have not been systematically examined. PURPOSE: The purpose of
      this study was to investigate the attitudes of CBOC providers about TMH services,
      current utilization of these technologies in their clinics, and sources of
      knowledge regarding TMH. METHOD: The study employed a mixed-methods design to
      examine aspects of TMH in CBOCs located in a VA network in the south-central
      United States. Semistructured, on-site group interviews conducted with 86 CBOC MH
      providers were followed by in-depth phone surveys with an MH provider identified
      as a key informant at each of 36 CBOCs in the VA network. FINDINGS: The
      utilization of TMH services varied widely between CBOCs, and the scope of
      services provided typically focused on delivery of medication management, with
      little provision of psychological services. Further, several important barriers
      to expanded use of TMH were identified, including limited education and training
      and shortage of dedicated space for TMH encounters. CONCLUSIONS: General
      attitudes toward TMH were positive, and most CBOC providers indicated that they
      would like to expand use of TMH in their clinics.

PMID- 21967389
TI  - Design of biomimetic catalysts by molecular imprinting in synthetic polymers: the
      role of transition state stabilization.
AB  - The impressive efficiency and selectivity of biological catalysts has engendered
      a long-standing effort to understand the details of enzyme action. It is widely
      accepted that enzymes accelerate reactions through their steric and electronic
      complementarity to the reactants in the rate-determining transition states. Thus,
      tight binding to the transition state of a reactant (rather than to the
      corresponding substrate) lowers the activation energy of the reaction, providing
      strong catalytic activity. Debates concerning the fundamentals of enzyme
      catalysis continue, however, and non-natural enzyme mimics offer important
      additional insight in this area. Molecular structures that mimic enzymes through
      the design of a predetermined binding site that stabilizes the transition state
      of a desired reaction are invaluable in this regard. Catalytic antibodies, which
      can be quite active when raised against stable transition state analogues of the
      corresponding reaction, represent particularly successful examples. Recently,
      synthetic chemistry has begun to match nature's ability to produce antibody-like
      binding sites with high affinities for the transition state. Thus, synthetic,
      molecularly imprinted polymers have been engineered to provide enzyme-like
      specificity and activity, and they now represent a powerful tool for creating
      highly efficient catalysts.  In this Account, we review recent efforts to develop
      enzyme models through the concept of transition state stabilization. In
      particular, models for carboxypeptidase A were prepared through the molecular
      imprinting of synthetic polymers. On the basis of successful experiments with
      phosphonic esters as templates to arrange amidinium groups in the active site,
      the method was further improved by combining the concept of transition state
      stabilization with the introduction of special catalytic moieties, such as metal
      ions in a defined orientation in the active site. In this way, the imprinted
      polymers were able to provide both an electrostatic stabilization for the
      transition state through the amidinium group as well as a synergism of transition
      state recognition and metal ion catalysis. The result was an excellent catalyst
      for carbonate hydrolysis. These enzyme mimics represent the most active catalysts
      ever prepared through the molecular imprinting strategy. Their catalytic
      activity, catalytic efficiency, and catalytic proficiency clearly surpass those
      of the corresponding catalytic antibodies.  The active structures in natural
      enzymes evolve within soluble proteins, typically by the refining of the folding
      of one polypeptide chain. To incorporate these characteristics into synthetic
      polymers, we used the concept of transition state stabilization to develop
      soluble, nanosized carboxypeptidase A models using a new polymerization method we
      term the "post-dilution polymerization method". With this methodology, we were
      able to prepare soluble, highly cross-linked, single-molecule nanoparticles.
      These particles have controlled molecular weights (39 kDa, for example) and, on
      average, one catalytically active site per particle. Our strategies have made it
      possible to obtain efficient new enzyme models and further advance the structural
      and functional analogy with natural enzymes. Moreover, this bioinspired design
      based on molecular imprinting in synthetic polymers offers further support for
      the concept of transition state stabilization in catalysis.

PMID- 21967390
TI  - The turbulent life of Sirevirus retrotransposons and the evolution of the maize
      genome: more than ten thousand elements tell the story.
AB  - Sireviruses are one of the three genera of Copia long terminal repeat (LTR)
      retrotransposons, exclusive to and highly abundant in plants, and with a unique,
      among retrotransposons, genome structure. Yet, perhaps due to the few references
      to the Sirevirus origin of some families, compounded by the difficulty in
      correctly assigning retrotransposon families into genera, Sireviruses have hardly
      featured in recent research. As a result, analysis at this key level of
      classification and details of their colonization and impact on plant genomes are
      currently lacking. Recently, however, it became possible to accurately assign
      elements from diverse families to this genus in one step, based on highly
      conserved sequence motifs. Hence, Sirevirus dynamics in the relatively obese
      maize genome can now be comprehensively studied. Overall, we identified >10 600
      intact and approximately 28 000 degenerate Sirevirus elements from a plethora of
      families, some brought into the genus for the first time. Sireviruses make up
      approximately 90% of the Copia population and it is the only genus that has
      successfully infiltrated the genome, possibly by experiencing intense
      amplification during the last 600 000 years, while being constantly recycled by
      host mechanisms. They accumulate in chromosome-distal gene-rich areas, where they
      insert in between gene islands, mainly in preferred zones within their own
      genomes. Sirevirus LTRs are heavily methylated, while there is evidence for a
      palindromic consensus target sequence. This work brings Sireviruses in the
      spotlight, elucidating their lifestyle and history, and suggesting their crucial
      role in the current genomic make-up of maize, and possibly other plant hosts.

PMID- 21967391
TI  - A practical approach to premature ejaculation. Introduction: the asynchronous
      couple.

PMID- 21967392
TI  - What does premature ejaculation mean to the man, the woman, and the couple?
AB  - INTRODUCTION: The relational impact of male and female sexual dysfunction, and
      specifically premature ejaculation (PE), is an important consideration. Published
      findings are consistent in identifying the negative psychosocial impact of PE on
      the man. However, the effect of PE on the female partner, especially in relation
      to her sexual functioning, has been less well studied. AIM: Provide an overview
      of the impact of PE on the man, the woman, and the couple. METHODS: Review of
      relevant literature. RESULTS: Female partners of men with PE report significantly
      greater sexual problems, with reduced satisfaction, increased distress and
      interpersonal difficulty, and more orgasmic problems than partners of non-PE men.
      Both men with PE and their partners feel control over ejaculation is the central
      issue in PE. For both, the lack of control leads to dissatisfaction, a feeling
      that something is missing from the relationship, and an impaired sense of
      intimacy. If left untreated, the situation can lead to increased irritability,
      interpersonal difficulties, and deepening of an emotional divide. CONCLUSIONS:
      When treating a man with PE, the partner's participation should be encouraged to
      enable the physician to fully understand the extent of the problem, and consider
      other relevant factors, from her perspective. Identifying the best approach for
      the couple requires consultation with each person individually and together. In
      clinical practice, treatments for PE are likely to include a combination of
      pharmacological, psychological, sexological, and/or behavioral approaches for
      both the man and his partner. It is important that physicians regard PE as the
      couple's problem and endeavor to include the partner in its management where
      possible.

PMID- 21967393
TI  - Neurophysiology of erection and ejaculation.
AB  - INTRODUCTION: Penile erection and ejaculation are closely associated during
      sexual intercourse. Erection is a central psychoneuroendocrine and peripheral
      neuro-vasculo-tissular event, resulting in blood filling the sinusoidal spaces of
      the corpora cavernosa and corpus spongiosum. Ejaculation represents the climax of
      the sexual cycle and comprises emission (secretion of semen) and expulsion
      (propulsion of semen) phases. AIM: This article provides an overview of the
      proposed neurophysiology of erection and ejaculation. METHODS: Review of the
      literature. MAIN OUTCOME MEASURES: Current data on the neurophysiology of
      erection and ejaculation. RESULTS: In terms of peripheral innervation, the pelvic
      plexus represents a junction for efferent nerves to the structures involved in
      erection and ejaculation. At the spinal level, the spinal cord contains three
      sets of neurons (thoracolumbar sympathetic, sacral parasympathetic, and somatic)
      innervating the sexual organs involved in erection and ejaculation. The presence
      of cerebral descending pathways to spinal erection and ejaculation centers
      indicates that the brain has an excitatory or inhibitory effect on these
      processes. Brain structures that modulate spinal command of erection and
      ejaculation are part of a larger network that is dedicated to regulating sexual
      responses. Neurophysiological and pharmacological research has elucidated that
      dopamine and serotonin have central roles in modulating erection and ejaculation.
      Interestingly, erection is not a prerequisite for ejaculation, and each of these
      sexual responses can exist without the other. CONCLUSION: Despite the association
      between erection and ejaculation during intercourse, these two processes can be
      considered distinct events from an anatomical, physiological, and pharmacological
      perspective.

PMID- 21967394
TI  - Pathophysiology of premature ejaculation.
AB  - INTRODUCTION: Although the characteristics of premature ejaculation (PE) are
      established, the exact aetiology is largely unknown. Genetic, neurobiological,
      pharmacological, psychological, urological and endocrine factors have all been
      proposed. In addition PE and erectile dysfunction are often co-morbid. AIM: This
      article provides an overview of the proposed biological and psychological
      aetiologies of PE. METHODS: Review of the literature. MAIN OUTCOME MEASURES:
      Current data on the pathophysiology of PE. RESULTS: This review shows that most
      of the proposed biological and psychological aetiologies of PE are not evidence
      based and/or that attempts to confirm them have given conflicting results. There
      are good data to support roles for genetic and psychological factors, either
      causal, or secondary to PE for the latter, in lifelong PE. Conversely, more
      evidence-based data support the responsibility of opioid substance withdrawal,
      prostatic inflammation or hyperthyroidism in some cases of acquired PE, in
      addition to a probable role of psychological factors. CONCLUSIONS: The
      determinants of PE are certainly complex and multifactorial, while each partner's
      reaction to the frustration caused by the sexual dysfunction may exacerbate or
      perpetuate it. It is important to understand, as far as possible, the aetiology
      in the individual patient to ensure appropriate assessment and treatment. It
      should be noted that identification of an aetiological factor does not
      necessarily mean the cause of the PE has been completely explained, and the
      patient may require a combination of treatment approaches.

PMID- 21967395
TI  - An overview of pharmacotherapy in premature ejaculation.
AB  - INTRODUCTION: With increasing interest and clinical research in male sexual
      disorders, it has become clear that not only psychological but also organic,
      neurobiological, and genetic factors may play an important role in premature
      ejaculation (PE). AIM: This article provides an overview of the different
      treatment options both for lifelong (primary, "congenital") and acquired
      (secondary) PE. METHODS: Review of the literature. MAIN OUTCOME MEASURES:
      Currently used treatment options for PE. RESULTS: Treatments reviewed include
      psychological/behavioral/sexual counseling therapy, topical anesthetics,
      dapoxetine, and other selective serotonin reuptake inhibitors (SSRIs), tricyclic
      antidepressants, and phosphodiesterase-5 (PDE-5) inhibitors. CONCLUSIONS: Before
      starting any therapy for PE, correct diagnosis has to be made considering the
      patient's reported intravaginal ejaculatory latency time (IELT) and the duration
      and type of PE. Concomitant erectile dysfunction (ED) should be either ruled out
      or proven by appropriate means. In uncomplicated cases of PE with stable
      partnerships, medical treatment represents the first-choice option with a high
      likelihood of success. Dapoxetine, where available, or other SSRIs provide
      suitable therapeutic options with a good risk/benefit profile for patients. In
      complicated ("difficult-to-treat") PE patients, a combination of medication and
      sexual counseling should be considered the first treatment option. Combination
      therapies of PDE-5 inhibitors and PE-related medications should be offered to
      patients suffering from comorbid PE and ED, with ED treatment starting first. In
      those patients with severe PE-IELTs of <30-60 seconds or anteportal ejaculation
      combination therapy of topical and oral medications can be offered and may
      considerably increase IELT, compared with either monotherapy.

PMID- 21967396
TI  - The importance of follow-up in patients with premature ejaculation.
AB  - INTRODUCTION: Follow-up is an important aspect of managing patients with
      premature ejaculation (PE). However, there is limited information for the
      clinician on the optimal follow-up regimen in men with PE. At present, follow-up
      remains largely at the discretion of each treating physician. AIM: The aim of
      this study was to provide an overview of follow-up in patients with PE. METHODS:
      This study used a review of the literature and informed expert opinion. MAIN
      OUTCOME MEASURES: The main outcome measures used by the study are the factors
      influencing follow-up in PE. RESULTS: Following up with the patient is important
      to reconfirm the diagnosis, assess the patient's progress on treatment, monitor
      efficacy and side effects and, where necessary, make informed adjustments to
      treatment. In addition, follow-up sessions provide an opportunity to reeducate
      the patient, check that they remember the key information, fill in missing gaps
      in knowledge, and ensure that they are adhering to the correct dosing schedule.
      The frequency and duration of follow-up visits depend on a number of factors,
      such as the type and severity of PE, type of treatment, durability of response to
      PE treatment, the presence of comorbidities and individual partner/partnership
      issues. A cooperative and interested partner often has positive effects on
      treatment outcomes. Therefore, the partner should be encouraged to attend follow
      up sessions for a better understanding of the impact of PE on their relationship
      and tailoring the treatment to suit the couple as a whole. CONCLUSIONS: In
      clinical practice, follow-up forms an essential component of the overall
      management of PE to help ensure optimal treatment outcomes.

PMID- 21967397
TI  - Case studies. A practical approach to premature ejaculation.

PMID- 21967398
TI  - Cutaneous verrucous carcinoma arising in lupus vulgaris.

PMID- 21967399
TI  - Reproducibility and diagnostic accuracy of three-layer speckle tracking
      echocardiography in a swine chronic ischemia model.
AB  - BACKGROUND: The subendocardial myocardium normally has higher systolic strain
      than the subepicardial myocardium and can be damaged first in face of ischemia.
      We investigated the reproducibility and feasibility of novel three-layer speckle
      tracking system and compared the diagnostic accuracy with experienced visual
      interpretation. METHODS: An ameroid constrictor was placed around the proximal
      left circumflex (LCX) coronary artery in 19 pigs. Four weeks later, subtotal
      stenosis was confirmed in all pigs by coronary angiogram. Two dead pigs and three
      pigs with pathological infarction were excluded. Transthoracic left ventricle
      (LV) short-axis echocardiograms were recorded at rest before and 4 weeks after
      the operation. LV posterior wall motion was scored by two experienced doctors and
      analyzed by the speckle tracking system (n = 14). RESULTS: Strain variables gave
      reasonable intra/interobserver reproducibility (mean absolute percentage errors =
      13/19, intraclass correlation coefficients = 0.97/0.92). All strain variables and
      visual wall-motion scores changed significantly during stenosis (P < 0.05). Of
      all variables, endocardial strains, particularly the circumferential strain
      demonstrated the highest area under curve (AUC), showing better diagnostic
      accuracy than experienced visual interpretation (sensitivity 0.93 vs. 0.79,
      specificity 0.93 vs. 0.73, AUC 0.95 vs. 0.77, P < 0.05). CONCLUSION: Three-layer
      speckle tracking is a feasible and reproducible modality. In particular,
      endocardial speckle tracking provides incremental value in accurately identifying
      regional ischemia even in the rest echocardiography.

PMID- 21967400
TI  - Possible role of epidermal growth factor receptors in the therapy of pancreatic
      cancer.
AB  - Pancreatic cancer is considered an 'orphan' cancer because of its relative low
      incidence. Unfortunately, even with early diagnosis, mortality rates are high and
      it ranks eighth in the worldwide ranking of deaths due to cancer. The
      administration of chemotherapeutic agents for the treatment of advanced disease
      has failed, and current research focuses on the understanding of molecular
      pathways in order to investigate the role of targeted therapy. It has been known
      that the development and the progression of pancreatic cancer are caused by the
      activation of oncogenes, the inactivation of tumor suppressor genes, and the
      deregulation of many signaling pathways of various growth factors, among which
      the epidermal growth factor receptor (EGFR) plays an important role. Growth
      factor receptors and their ligands not only regulate normal cell processes, but
      have also been identified as key regulators of human cancer formation. EGFR has
      been found to be expressed and altered in pancreatic cancer and clearly plays a
      significant role in tumor development and progression, including cell
      proliferation, regulation of apoptotic cell death, angiogenesis, and metastatic
      spread. The amplitude and kinetics of growth factor signaling are determined
      mainly by a highly regulated endocytic process that sorts and directs activated
      receptors to degradation in lysosomes. Therefore, EGFR is a legitimate
      therapeutic target. The aim of this review is to outline the endocytic escape of
      EGFRs in cancer with special attention towards recent advances in various
      approaches adopted for EGFR targeting.

PMID- 21967401
TI  - Lipid nanocarriers: influence of lipids on product development and
      pharmacokinetics.
AB  - Lipid nanocarriers are on the forefront of the rapidly developing field of
      nanotechnology with several potential applications in drug delivery. Owing to
      their size-dependent properties, lipid nanoparticles offer the possibility for
      development of new therapeutics and an alternative system to other colloidal
      counterparts for drug administration. An important point to be considered in the
      selection of a lipid for the carrier system is its effect on the properties of
      the nanocarrier and also its intended use, as different types of lipids differ in
      their nature. Researchers around the globe have tapped the potential of solid
      lipid nanoparticles (SLNs) in developing formulation(s) that can be administered
      by various routes such as oral, ocular, parenteral, topical, and pulmonary. Since
      the start of this millennium, a new generation of lipid nanoparticles, namely
      nanostructured lipid carriers (NLCs), lipid drug conjugates (LDCs), and
      pharmacosomes, has evolved that have the potential to overcome the limitations of
      SLNs. The current review article presents broad considerations on the influence
      of various types of lipids on the diverse characteristics of nanocarriers,
      encompassing their  physicochemical, formulation, pharmacokinetic, and cytotoxic
      aspects.

PMID- 21967402
TI  - Advancing description and explanation in clinical linguistics: a legacy of Martin
      J. Ball.
AB  - This article asserts the importance of explication of order and disorder in
      language as a privileged objective of clinical linguistics and service delivery
      and reviews the contributions of Martin Ball in advancing this agenda.

PMID- 21967403
TI  - Photoswitchable organic mixed valence in dithienylcyclopentene  systems with
      tertiary amine redox centers.
AB  - The electronic structures of the radical cations of two
      dithienylperfluorocyclopentene molecules with appended tertiary amine units were
      investigated by electrochemical and optical spectroscopic methods. The through
      bond N-N distances in the photocyclized (closed) forms of the two systems are 9.3
      and 17.6 A, respectively, depending on whether the nitrogen atoms are attached
      directly to the two thienyl units or whether xylyl spacers are in between. In the
      case of the radical cation with the longer N-N distance, photocyclization of the
      dithienylperfluorocyclopentene core induces a changeover from class I to class II
      mixed valence behavior. In the case of the shorter system, the experimental data
      is consistent with assignment of the photocyclized form to a class III mixed
      valence species.

PMID- 21967404
TI  - Horizontal transfer of dehalogenase genes involved in the catalysis of
      chlorinated compounds: evidence and ecological role.
AB  - Horizontal gene transfer (HGT) of dehalogenase genes is considered an important
      mechanism of genomic evolution, the metabolic resilience of biotopes, and
      microbial community adaptation in chlorinated compound-contaminated ecosystems.
      In this review, we summarize the current evidence for the HGT of dehalogenase
      genes involved in the catalysis of various chlorinated compounds, such as
      chlorinated alkanes and alkanoic acids, chlorinated ethenes, chlorinated
      herbicide, and chlorinated aromatics. We also highlight the ecological role of
      HGT as it relates to the contribution to the diversification of dehalogenating
      microorganisms and the resulting facilitation of rapid microbial community
      adaptation to ecosystem contaminated with chlorinated compounds.

PMID- 21967405
TI  - Template effect in the competition between Haeckelite and graphene growth on
      Ni(111): quantum chemical molecular dynamics simulations.
AB  - Quantum chemical molecular dynamics (QM/MD) simulations of ensembles of C(2)
      molecules on the Ni(111) terrace show that, in the absence of a hexagonal
      template or step edge, Haeckelite is preferentially nucleated over graphene as a
      metastable intermediate. The nucleation process is dominated by the swift
      transition of long carbon chains toward a fully connected sp(2) carbon network.
      Starting from a pentagon as nucleus, pentagons and heptagons condense during ring
      collapse reactions, which results in zero overall curvature. To the contrary, in
      the presence of a coronene-like C(24) template, hexagonal ring formation is
      clearly promoted, in agreement with recent suggestions from experiments. In the
      absence of step edges or molecular templates, graphene nucleation follows
      Ostwald's "rule of stages" cascade of metastable states, from linear carbon
      chains, via Haeckelite islands that finally anneal to graphene.

PMID- 21967406
TI  - In(x)Ga(1-x)As nanowires on silicon: one-dimensional heterogeneous epitaxy,
      bandgap engineering, and photovoltaics.
AB  - We report on the one-dimensional (1D) heteroepitaxial growth of In(x)Ga(1-x)As (x
      = 0.2-1) nanowires (NWs) on silicon (Si) substrates over almost the entire
      composition range using metalorganic chemical vapor deposition (MOCVD) without
      catalysts or masks. The epitaxial growth takes place spontaneously producing
      uniform, nontapered, high aspect ratio NW arrays with a density exceeding 1 *
      10(8)/cm(2). NW diameter (~30-250 nm) is inversely proportional to the lattice
      mismatch between In(x)Ga(1-x)As and Si (~4-11%), and can be further tuned by
      MOCVD growth condition. Remarkably, no dislocations have been found in all
      composition In(x)Ga(1-x)As NWs, even though massive stacking faults and twin
      planes are present. Indium rich NWs show more zinc-blende and Ga-rich NWs exhibit
      dominantly wurtzite polytype, as confirmed by scanning transmission electron
      microscopy (STEM) and photoluminescence spectra. Solar cells fabricated using an
      n-type In(0.3)Ga(0.7)As NW array on a p-type Si(111) substrate with a ~ 2.2% area
      coverage, operates at an open circuit voltage, V(oc), and a short circuit current
      density, J(sc), of 0.37 V and 12.9 mA/cm(2), respectively. This work represents
      the first systematic report on direct 1D heteroepitaxy of ternary In(x)Ga(1-x)As
      NWs on silicon substrate in a wide composition/bandgap range that can be used for
      wafer-scale monolithic heterogeneous integration for high performance
      photovoltaics.

PMID- 21967407
TI  - Comparison of immunological parameters in patients with pemphigus vulgaris
      following rituximab and IVIG therapy.
AB  - BACKGROUND: Information on certain immunological parameters in patients with
      pemphigus vulgaris (PV) treated with rituximab (RTX) and intravenous
      immunoglobulin (IVIG) therapy is limited. OBJECTIVE: Comparing immunological
      parameters in patients who achieved long-term clinical remission (LTR) with those
      who relapsed. METHODS: Retrospective analysis of 19 patients treated at a single
      centre using the same protocol. Comparisons were made between patients who went
      into LTR and those who relapsed following completion of the protocol. Treatments
      prior to IVIG and RTX included prednisone with or without an immunosuppressive
      agent. The immunological parameters measured included peripheral blood B cells
      (CD19+), serum quantitative immunoglobulin levels, and levels of antibodies to
      desmogleins (Dsg) 1 and 3. RESULTS: Eleven patients achieved LTR. Eight patients
      developed 15 relapses. The mean follow-up time for the LTR group was 29.6+/
      11.2months, and for the relapse group, 40.0+/-7.0 months. There were no
      significant differences in times to B-cell depletion, repopulation, or recovery
      to pretreatment levels between the patients who achieved LTR and those who
      relapsed. Recurrences usually occurred after B-cell repopulation. Repeated
      treatments did not influence the time to B-cell repopulation. IgM levels were
      decreased after therapy and remained decreased. A consistent increase in anti
      Dsg1 antibody levels occurred at the time of relapse in patients with
      mucocutaneous disease. CONCLUSIONS: The majority of patients treated with
      rituximab and IVIG therapy achieved LTR. Retreatment of relapses can induce LTR.
      Decreased serum IgM levels persisted following treatment. Increases in anti-Dsg1
      antibodies during therapy in patients with mucocutaneous disease suggests a close
      follow-up for a potential relapse is required.

PMID- 21967408
TI  - Phenomenon of declining blood pressure in elderly--high systolic levels are
      undervalued with Korotkoff method.
AB  - BACKGROUND: Systolic blood pressure (SBP) decline has been reported in
      octogenarians. The aim was to study if it could be observed while measuring SBP
      with two methods: Korotkoff (K-BP) and Strain-Gauge-Finger-Plethysmography (SG
      BP), and which of them were more reliable in expressing vascular burden. METHODS:
      A cohort of 703 men from a population of Malmo, Sweden, were included in "Men
      born in 1914-study" and followed-up at ages: 68 and 81 years. 176 survivors were
      examined with K-BP and SG-BP at both ages, and 104 of them with Ambulatory Blood
      Pressure at age 81/82. Ankle Brachial Index (ABI) was measured on both occasions,
      and Carotid Ultrasound at age 81. RESULTS: From age 68 to 81, mean K-BP decreased
      in the cohort with mean 8.3 mmHg, while SG-BP increased with 13.4 mmHg. K-BP
      decreased in 55% and SG-BP in 31% of the subjects. At age 81, K-BP was lower than
      SG-BP in 72% of subjects, and correlated to high K-BP at age 68 (r = --.22; p <
      .05). SG-BP at age 81 was correlated with mean ambulatory 24-h SBP (r = .480; p <
      .0001), daytime SBP (r = .416; p < .0001), nighttime SBP (r = .395; p < .0001),
      and daytime and nighttime Pulse Pressure (r = .452; p < .0001 and r = .386; p <
      .0001). KB-BP correlated moderately only with nighttime SBP (r = .198; p = .044),
      and daytime and nightime pulse pressure (r = .225; p = .021 and r = .264; p =
      .007). Increasing SG-BP from age 68 to 81, but not K-BP, correlated with: 24-h,
      daytime and nighttime SBP, and mean daytime and nighttime Pulse Pressure.
      Increasing SG-BP was also predicted by high B-glucose and low ABI at age 68, and
      correlated with carotid stenosis and low ABI age 81, and the grade of ABI
      decrease over 13 years. CONCLUSION: In contrast to K-BP, values of SG-BP in
      octogenarians strongly correlated with Ambulatory Blood Pressure. The SG-BP
      decline in the last decade was rare, and increasing SG-BP better than K-BP
      reflected advanced atherosclerosis. It should be aware, that K-BP underdetected
      46% of subjects with SG-BP equal/higher than 140 mmHg at age 81, which may lead
      to biased associations with risk factors due to differential misclassification by
      age.

PMID- 21967409
TI  - Zonisamide in the treatment of epilepsy.
AB  - INTRODUCTION: Epilepsy affects approximately 3 million people in the USA and up
      to 2% of the worldwide population. The yearly direct medical cost of epilepsy in
      the USA alone is estimated to be $9.5 billion. Epilepsy affects both children and
      adults and can significantly impair quality of life. Zonisamide is a second
      generation antiepileptic drug (AED) that has broad-spectrum efficacy, a favorable
      side-effect profile and simpler dosing than earlier drugs. AREAS COVERED: The
      history of the development of zonisamide is reviewed in this paper. The data
      available demonstrating zonisamide's mechanism of action as a voltage-gated
      sodium channel inhibitor, a T-type calcium channel inhibitor, an enhancer of GABA
      release and an inhibitor of glutamate release are also reviewed. Four key Phase
      III clinical trials are reviewed in detail, as are subsequent postmarketing
      trials that have expanded the therapeutic indication for zonisamide. EXPERT
      OPINION: From the available clinical data, zonisamide is a viable first-line and
      adjunctive therapeutic for partial-onset epilepsy and should be considered as an
      adjunctive therapeutic for a wide-range of generalized epilepsies.

PMID- 21967410
TI  - Incidence and outcome of tube thoracostomy positioning in trauma patients.
AB  - OBJECTIVES: To evaluate the frequency of use, placement site, success and
      misplacement rates, and need for intervention for tube thoracostomies (TTs), and
      the complications with endotracheal intubation associated with TT in the
      prehospital setting. METHODS: We performed a five-year, retrospective study using
      the records of 1,065 patients who were admitted to the trauma emergency room at a
      university hospital and who had received chest radiographs or computed tomography
      (CT) scans within 30 minutes after admission. RESULTS: Seven percent of all
      patients received a TT (5% unilateral, 2% bilateral). Ninety-seven percent of all
      patients with a TT were endotracheally intubated. The success rate for correctly
      placed chest tubes was 78%. Twenty-two percent of the chest tubes were misplaced
      (i.e., too far in the chest, twisted, or bent); half of those had to be
      corrected, with one needing to be replaced. There were no statistical differences
      in the frequency of Monaldi or Bulau positions, or the frequency of left or right
      chest TT. In addition, the two positions did not differ in misplacement rates or
      the need for intervention. Helicopter emergency medical services physicians used
      the Monaldi position significantly more frequently than the Bulau position. In
      hospital physicians performing interhospital transfer used the Bulau position
      significantly more frequently, whereas ground emergency medical physicians had a
      more balanced relationship between the two positions. Tube thoracostomy had no
      influence on endotracheal tube misplacement rates, and vice versa. CONCLUSION:
      Tube thoracostomy positioning mostly depends on the discretion of the physician
      on scene. The Monaldi and Bulau positions do not differ in misplacement or
      complication rates.

PMID- 21967411
TI  - Not letting the ideal be the enemy of the good: the case of the Better Access
      evaluation.

PMID- 21967412
TI  - Affective and anxiety disorders and their relationship with chronic physical
      conditions in Australia: findings of the 2007 National Survey of Mental Health
      and Wellbeing.
AB  - OBJECTIVE: The aim of this study was to report nationally representative data on
      the prevalence and patterns of 12 month comorbidity of chronic physical
      conditions (diabetes, asthma, coronary heart disease, stroke, cancer, arthritis)
      and DSM-IV affective and anxiety disorders in Australian adults. METHOD: The 2007
      National Survey of Mental Health and Wellbeing (NSMHWB) was a nationally
      representative household survey of 8841 Australian adults (16-85 years) assessing
      symptoms of ICD-10 mental disorders and the presence of chronic physical
      conditions. RESULTS: Prevalence of at least one National Health Priority Area
      chronic physical condition was 32.2% (95%CI = 30.9%-33.5%). Among those with
      chronic physical conditions 21.9% had an affective or anxiety disorder. Affective
      and anxiety disorders were more common among people with physical conditions than
      among people without chronic physical conditions (affective OR 1.5; anxiety OR
      1.8). Of those with a 12 month affective or anxiety disorder, 45.6% had a chronic
      physical condition. Physical disorders were more common in those with an
      affective or anxiety disorder than among people without an affective or anxiety
      disorder (affective OR 1.6; anxiety OR 2.0). Disability was high in those with an
      anxiety disorder, an affective disorder and a physical condition and 43.4% were
      classified as high service users. CONCLUSIONS: Comorbidity between chronic
      physical conditions and affective and anxiety disorders is widespread and is
      associated with high levels of disability and service use.

PMID- 21967413
TI  - RE: PBS delisting.

PMID- 21967414
TI  - Novel surface display system for heterogonous proteins on Lactobacillus
      plantarum.
AB  - AIMS: To establish a novel cell surface display system that would enable the
      display of target proteins on Lactobacillus plantarum. METHODS AND RESULTS:
      BlastP analysis of the amino acids sequence data revealed that the N-terminus of
      the putative muropeptidase MurO from L. plantarum contained two putative lysin
      motif (LysM) repeat regions, implying that the MurO was involved in bacterial
      cell wall binding. To investigate the potential of MurO for surface display,
      green fluorescent protein (GFP) was fused to MurO at its C-terminus and the
      resulting fusion protein was expressed in Escherichia coli. After being mixed
      with L. plantarum cells in vitro, GFP was successfully displayed on the surfaces
      of L. plantarum cells. Increases in the fluorescence intensities of chemically
      pretreated L. plantarum cells compared to those of nonpretreated cells suggested
      that the peptidoglycan was the binding ligand for MurO. SDS sensitivity assay
      showed that the GFP fluorescence intensity was reduced after being treated with
      SDS. To demonstrate the applicability of the MurO-mediated surface display
      system, beta-galactosidase from Bifidobacterium bifidium, in place of GFP, was
      functionally displayed on the surface of L. plantarum cells via MurO.
      CONCLUSIONS: The MurO was a novel anchor protein for constructing a surface
      display system for L. plantarum. SIGNIFICANCE AND IMPACT OF STUDY: The success in
      surface display of GFP and beta-galactosidase opened up the feasibility of
      employing the cell wall anchor of MurO for surface display in L. plantarum.

PMID- 21967415
TI  - The evolution of punishment in n-player public goods games: a volunteer's
      dilemma.
AB  - The evolution of punishment to stabilize cooperation in n-player games has been
      treated as a second-order social dilemma, where contributions to punishment of
      free-riders are altruistic. Hence it may only evolve under highly restricted
      conditions. Here, we build on recent insights using the volunteer's dilemma as an
      alternative payoff matrix for the evolution of cooperation. The key feature of a
      volunteer's dilemma is that the benefits of cooperation are a nonlinear function
      of the number of contributors, meaning that cooperation is negatively frequency
      dependent. We propose that nonlinear returns are also an inherent feature of
      punishment and that this insight allows for a simple and novel explanation of how
      punishment evolves in groups.

PMID- 21967416
TI  - Are greenbeards intragenomic outlaws?
AB  - Greenbeard genes identify copies of themselves in other individuals and cause
      their bearer to behave nepotistically toward those individuals. Hence, they can
      be favored by kin selection, irrespective of the degree of genealogical
      relationship between social partners. Although greenbeards were initially
      developed as a thought experiment, a number of recent discoveries of greenbeard
      alleles in real populations have led to a resurgence of interest in their
      evolutionary dynamics and consequences. One issue over which there has been
      disagreement is whether greenbeards lead to intragenomic conflict. Here, to
      clarify the "outlaw" status of greenbeards, we develop population genetic models
      that formally examine selection of greenbeard phenotypes under the control of
      different loci. We find that, in many cases, greenbeards are not outlaws because
      selection for or against the greenbeard phenotype is the same across all loci. In
      contrast, when social interactions are between genealogical kin, we find that
      greenbeards can be outlaws because different genes can be selected in different
      directions. Hence, the outlaw status of greenbeard genes crucially depends upon
      the particular biological details. We also clarify whether greenbeards are
      favored due to direct or indirect fitness effects and address the relationship of
      the greenbeard effect to sexual antagonism and reciprocity.

PMID- 21967417
TI  - Some mistakes go unpunished: the evolution of "all or nothing" signalling.
AB  - Many models of honest signaling, based on Zahavi's handicap principle, predict
      that if receivers are interested in a quality that shows continuous variation
      across the population of signalers, then the distribution of signal intensities
      will also be continuous. However, it has previously been noted that this
      prediction does not agree with empirical observation in many signaling systems,
      where signals are limited to a small number of levels despite continuous
      variation in the trait being signaled. Typically, there is a critical value of
      the trait, with all individuals with trait values on one side of the threshold
      using the same cheap signal, and all those with trait values on the other side of
      the threshold using the same expensive signal. It has already been demonstrated
      that these classical models naturally predict such "all-or-nothing signaling" if
      it is additionally assumed that receivers suffer from perceptual error in
      evaluating signal strength. We show that such all-or-nothing signaling is also
      predicted if receivers are limited to responding to the signals in one of two
      ways. We suggest that many ecological situations (such as the decision to attack
      the signaler or not, or mate with the signaler or not) involve such binary
      choices.

PMID- 21967418
TI  - Density-dependent cooperation as a mechanism for persistence and coexistence.
AB  - To overcome stress, such as resource limitation, an organism often needs to
      successfully mediate competition with other members of its own species. This may
      favor the evolution of defective traits that are harmful to the species
      population as a whole, and that may lead to its dilution or even to its
      extinction (the tragedy of the commons). Here, we show that this phenomenon can
      be circumvented by cooperation plasticity, in which an individual decides, based
      on environmental conditions, whether to cooperate or to defect. Specifically, we
      analyze the evolution of density-dependent cooperation. In our model, the
      population is spatially subdivided, periodically remixed, and comprises several
      species. We find that evolution pushes individuals to be more cooperative when
      their own species is at lower densities, and we show that not only could this
      cooperation prevent the tragedy of the commons, but it could also facilitate
      coexistence between many species that compete for the same resource.

PMID- 21967419
TI  - The evolution of teaching.
AB  - Teaching, alongside imitation, is widely thought to underlie the success of
      humanity by allowing high-fidelity transmission of information, skills, and
      technology between individuals, facilitating both cumulative knowledge gain and
      normative culture. Yet, it remains a mystery why teaching should be widespread in
      human societies but extremely rare in other animals. We explore the evolution of
      teaching using simple genetic models in which a single tutor transmits adaptive
      information to a related pupil at a cost. Teaching is expected to evolve where
      its costs are outweighed by the inclusive fitness benefits that result from the
      tutor's relatives being more likely to acquire the valuable information. We find
      that teaching is not favored where the pupil can easily acquire the information
      on its own, or through copying others, or for difficult to learn traits, where
      teachers typically do not possess the information to pass on to relatives. This
      leads to a narrow range of traits for which teaching would be efficacious, which
      helps to explain the rarity of teaching in nature, its unusual distribution, and
      its highly specific nature. Further models that allow for cumulative cultural
      knowledge gain suggest that teaching evolved in humans because cumulative culture
      renders otherwise difficult-to-acquire valuable information available to teach.

PMID- 21967420
TI  - Phenotypic assortment mediates the effect of social selection in a wild beetle
      population.
AB  - Social interactions often have major fitness consequences, but little is known
      about how specific interacting phenotypes affect the strength of natural
      selection. Social influences on the evolutionary process can be assessed using a
      multilevel selection approach that partitions the effects of social partner
      phenotypes on fitness (referred to as social or group selection) from those of
      the traits of a focal individual (nonsocial or individual selection). To quantify
      the contribution of social selection to total selection affecting a trait, the
      patterns of phenotypic association among interactants must also be considered. We
      estimated selection gradients on male body size in a wild population of forked
      fungus beetles (Bolitotherus cornutus). We detected positive nonsocial selection
      and negative social selection on body size operating through differences in
      copulation success, indicating that large males with small social partners had
      highest fitness. In addition, we found that, in low-density demes, the phenotypes
      of focal individuals were negatively correlated with those of their social
      partners. This pattern reversed the negative effect of group selection on body
      size and led to stronger positive selection for body size. Our results
      demonstrate multilevel selection in nature and stress the importance of
      considering social selection whenever conspecific interactions occur nonrandomly.

PMID- 21967421
TI  - The evolution of males: support for predictions from sex allocation theory using
      mating arrays of sagittaria latifolia (alismataceae).
AB  - Investment in male function should often yield diminishing fitness returns,
      subjecting the evolution of male phenotypes to substantial constraints. In
      plants, the subdivision of male function via the gradual presentation of pollen
      might minimize these constraints by preventing the saturation of receptive
      stigmas. Here, we report on an investigation of (1) patterns of investment in
      male function by plants in hermaphroditic (monoecious) and dioecious populations
      of Sagittaria latifolia, and (2) patterns of siring success by males versus
      hermaphrodites in experimental mating arrays. We show that in natural
      populations, males from dioecious populations had greater investment in male
      function than hermaphrodites in monoecious populations. However, as a proportion
      of total flower production, males presented substantially fewer flowers at once
      than hermaphrodites. In comparison with hermaphrodites, therefore, males
      prolonged the period over which they presented pollen. In mating arrays comprised
      of females, males, and hermaphrodites, siring success by males increased linearly
      with flower production. This finding is consistent with the existence of a linear
      gain curve for male function in S. latifolia and supports the idea that the
      gradual deployment of male function enables plants to avoid diminishing returns
      on the investment in male function.

PMID- 21967422
TI  - Context-dependent sex allocation: constraints on the expression and evolution of
      maternal effects.
AB  - Despite decades of research, whether vertebrates can and do adaptively adjust the
      sex ratio of their offspring is still highly debated. However, this may have
      resulted from the failure of empirical tests to identify large and predictable
      fitness returns to females from strategic adjustment. Here, we test the effect of
      diet quality and maternal condition on facultative sex ratio adjustment in the
      color polymorphic Gouldian finch (Erythrura gouldiae), a species that exhibits
      extreme maternal allocation in response to severe and predictable (genetically
      determined) fitness costs. On high-quality diets, females produced a relatively
      equal sex ratio, but over-produced sons in poor dietary conditions. Despite the
      lack of sexual size dimorphism, nutritionally stressed foster sons were
      healthier, grew faster, and were more likely to survive than daughters. Although
      these findings are in line with predictions from sex allocation theory, the
      extent of adjustment is considerably lower than previously reported for this
      species. Females therefore have strong facultative control over sex allocation,
      but the extent of adjustment is likely determined by the relative magnitude of
      fitness gains and the ability to reliably predict sex-specific benefits from
      environmental (vs. genetic) variables. These findings may help explain the often
      inconsistent, weak, or inconclusive empirical evidence for adaptive sex ratio
      adjustment in vertebrates.

PMID- 21967423
TI  - Do variations in substitution rates and male mutation bias correlate with life
      history traits? A study of 32 mammalian genomes.
AB  - Life-history traits vary substantially across species, and have been demonstrated
      to affect substitution rates. We compute genome-wide, branch-specific estimates
      of male mutation bias (the ratio of male-to-female mutation rates) across 32
      mammalian genomes and study how these vary with life-history traits (generation
      time, metabolic rate, and sperm competition). We also investigate the influence
      of life-history traits on substitution rates at unconstrained sites across a wide
      phylogenetic range. We observe that increased generation time is the strongest
      predictor of variation in both substitution rates (for which it is a negative
      predictor) and male mutation bias (for which it is a positive predictor).
      Although less significant, we also observe that estimates of metabolic rate,
      reflecting replication-independent DNA damage and repair mechanisms, correlate
      negatively with autosomal substitution rates, and positively with male mutation
      bias. Finally, in contrast to expectations, we find no significant correlation
      between sperm competition and either autosomal substitution rates or male
      mutation bias. Our results support the important but frequently opposite effects
      of some, but not all, life-history traits on substitution rates.

PMID- 21967424
TI  - Reducing mutation load through sexual selection on males.
AB  - Mutation load is a key parameter in evolutionary theories, but relatively little
      empirical information exists on the mutation load of populations, or the
      elimination of this load through selection. We manipulated the opportunity for
      sexual selection within a mutation accumulation divergence experiment to
      determine how sexual selection on males affected the accumulation of mutations
      contributing to sexual and nonsexual fitness. Sexual selection prevented the
      accumulation of mutations affecting male mating success, the target trait, as
      well as reducing mutation load on productivity, a nonsexual fitness component.
      Mutational correlations between mating success and productivity (estimated in the
      absence of sexual selection) were positive. Sexual selection significantly
      reduced these fitness component correlations. Male mating success significantly
      diverged between sexual selection treatments, consistent with the fixation of
      genetic differences. However, the rank of the treatments was not consistent
      across assays, indicating that the mutational effects on mating success were
      conditional on biotic and abiotic context. Our experiment suggests that greater
      insight into the genetic targets of natural and sexual selection can be gained by
      focusing on mutational rather than standing genetic variation, and on the
      behavior of trait variances rather than means.

PMID- 21967425
TI  - High temperatures reveal cryptic genetic variation in a polymorphic female sperm
      storage organ.
AB  - Variation in female reproductive morphology may play a decisive role in
      reproductive isolation by affecting the relative fertilization success of
      alternative male phenotypes. Yet, knowledge of how environmental variation may
      influence the development of the female reproductive tract and thus alter the
      arena of postcopulatory sexual selection is limited. Yellow dung fly females
      possess either three or four sperm storage compartments, a polymorphism with
      documented influence on sperm precedence. We performed a quantitative genetics
      study including 12 populations reared at three developmental temperatures
      complemented by extensive field data to show that warm developmental temperatures
      increase the frequency of females with four compartments, revealing striking
      hidden genetic variation for the polymorphism. Systematic genetic differentiation
      in growth rate and spermathecal number along latitude, and phenotypic covariance
      between the traits across temperature treatments suggest that the genetic
      architecture underlying the polymorphism is shaped by selection on metabolic
      rate. Our findings illustrate how temperature can modulate the preconditions for
      sexual selection by differentially exposing novel variation in reproductive
      morphology. This implies that environmental change may substantially alter the
      dynamics of sexual selection. We further discuss how temperature-dependent
      developmental plasticity may have contributed to observed rapid evolutionary
      transitions in spermathecal morphology.

PMID- 21967426
TI  - Sexual selection drives the evolution of antiaphrodisiac pheromones in
      butterflies.
AB  - Competition for mates has resulted in sophisticated mechanisms of male control
      over female reproduction. Antiaphrodisiacs are pheromones transferred from males
      to females during mating that reduce attractiveness of females to subsequent
      courting males. Antiaphrodisiacs generally help unreceptive females reduce male
      harassment. However, lack of control over pheromone release by females and male
      control over the amount transferred provides males an opportunity to use
      antiaphrodisiacs to delay remating by females that have returned to a receptive
      state. We propose a model for the evolution of antiaphrodisiacs under the
      influence of intrasexual selection, and determine whether changes in this signal
      in 11 species of Heliconius butterflies are consistent with two predictions of
      the model. First, we find that as predicted, male-contributed chemical mixtures
      are complex and highly variable across species, with limited phylogenetic signal.
      Second, differences in rates of evolution in pheromone composition between two
      major clades of Heliconius are as expected: the clade with a greater potential
      for male-male competition (polyandrous) shows a faster rate of divergence than
      the one with typically monoandrous mating system. Taken together, our results
      provide evidence that for females, antiaphrodisiacs can be both honest signals of
      receptivity (helping reduce harassment) and chastity belts (a male-imposed
      reduction in remating).

PMID- 21967427
TI  - Decoupling of rapid and adaptive evolution among seminal fluid proteins in
      heliconius butterflies with divergent mating systems.
AB  - Reproductive proteins often diverge rapidly between species. This pattern is
      frequently attributed to postmating sexual selection. Heliconius butterflies
      offer a good opportunity to examine this hypothesis by contrasting patterns of
      reproductive protein evolution between clades with divergent mating systems.
      Pupal-mating Heliconius females typically mate only once, limiting opportunity
      for postmating sexual selection. In contrast, adult-mating females remate
      throughout life. Reproductive protein evolution is therefore predicted to be
      slower and show little evidence of positive selection in the pupal-mating clade.
      We examined this prediction by sequencing 18 seminal fluid protein genes from a
      dozen Heliconius species and a related outgroup. Two proteins exhibited dN/dS >
      1, implicating positive selection in the rapid evolution of at least a few
      Heliconius seminal fluid proteins. However, contrary to predictions, the average
      evolutionary rate of seminal fluid proteins was greater among pupal-mating
      Heliconius. Based on these results, we suggest that positive selection and
      relaxed constraint can generate conflicting patterns of reproductive protein
      evolution between mating systems. As predicted, some loci may show elevated
      evolutionary rates in promiscuous taxa relative to monandrous taxa resulting from
      adaptations to postmating sexual selection. However, when monandry is derived (as
      in Heliconius), the opposite pattern may result from relaxed selective
      constraints.

PMID- 21967428
TI  - Elimination of a genetic correlation between the sexes via artificial
      correlational selection.
AB  - Genetic correlations between the sexes can constrain the evolution of sexual
      dimorphism and be difficult to alter, because traits common to both sexes share
      the same genetic underpinnings. We tested whether artificial correlational
      selection favoring specific combinations of male and female traits within
      families could change the strength of a very high between-sex genetic correlation
      for flower size in the dioecious plant Silene latifolia. This novel selection
      dramatically reduced the correlation in two of three selection lines in fewer
      than five generations. Subsequent selection only on females in a line
      characterized by a lower between-sex genetic correlation led to a significantly
      lower correlated response in males, confirming the potential evolutionary impact
      of the reduced correlation. Although between-sex genetic correlations can
      potentially constrain the evolution of sexual dimorphism, our findings reveal
      that these constraints come not from a simple conflict between an inflexible
      genetic architecture and a pattern of selection working in opposition to it, but
      rather a complex relationship between a changeable correlation and a form of
      selection that promotes it. In other words, the form of selection on males and
      females that leads to sexual dimorphism may also promote the genetic phenomenon
      that limits sexual dimorphism.

PMID- 21967429
TI  - Male-female coevolution in the wild: evidence from a time series in artemia
      franciscana.
AB  - Sexual conflicts are ubiquitous in nature and are expected to lead to an
      antagonistic coevolution between the sexes. This coevolutionary process is driven
      by selection on sexually antagonistic traits that can either be directional or
      fluctuating. In this study, we used dormant cysts of Artemia franciscana,
      collected in the same population in three different years over a 23-year period
      (corresponding to ~160 generations in this system), to investigate male-female
      coevolution in natural conditions over time. We performed a cross experiment
      study where reproduction of females mated to males from the past, present, or
      future was monitored until death. In agreement with a model of "fluctuating
      selection," we found that females survived better and had longer interbrood
      intervals when mated with their contemporary males compared to when mated with
      males from the future or the past. However, female weekly and lifetime
      reproductive successes displayed no differences between contemporary and
      noncontemporary matings. Finally, the coevolutionary patterns ("arms race
      dynamics" or "fluctuating selection dynamics") possibly acting on female relative
      fitness could not be discriminated. This study is the first direct demonstration
      that the process of male-female coevolution, previously revealed by experimental
      evolution in laboratory artificial conditions, can occur in nature on a short
      evolutionary time scale.

PMID- 21967430
TI  - Evolution of a plastic quantitative trait in an age-structured population in a
      fluctuating environment.
AB  - We analyze weak fluctuating selection on a quantitative character in an age
      structured population not subject to density regulation. We assume that early in
      the first year of life before selection, during a critical state of development,
      environments exert a plastic effect on the phenotype, which remains constant
      throughout the life of an individual. Age-specific selection on the character
      affects survival and fecundity, which have intermediate optima subject to
      temporal environmental fluctuations with directional selection in some age
      classes as special cases. Weighting individuals by their reproductive value, as
      suggested by Fisher, we show that the expected response per year in the weighted
      mean character has the same form as for models with no age structure.
      Environmental stochasticity generates stochastic fluctuations in the weighted
      mean character following a first-order autoregressive model with a temporally
      autocorrelated noise term and stationary variance depending on the amount of
      phenotypic plasticity. The parameters of the process are simple weighted averages
      of parameters used to describe age-specific survival and fecundity. The "age
      specific selective weights" are related to the stable distribution of
      reproductive values among age classes. This allows partitioning of the change in
      the weighted mean character into age-specific components.

PMID- 21967431
TI  - Genetic components to caste allocation in a multiple-queen ant species.
AB  - Reproductive division of labor and the coexistence of distinct castes are
      hallmarks of insect societies. In social insect species with multiple queens per
      colony, the fitness of nestmate queens directly depends on the process of caste
      allocation (i.e., the relative investment in queen, sterile worker and male
      production). The aim of this study is to investigate the genetic components to
      the process of caste allocation in a multiple-queen ant species. We conducted
      controlled crosses in the Argentine ant Linepithema humile and established single
      queen colonies to identify maternal and paternal family effects on the relative
      production of new queens, workers, and males. There were significant effects of
      parental genetic backgrounds on various aspects of caste allocation: the paternal
      lineage affected the proportion of queens and workers produced whereas the
      proportions of queens and males, and females and males were influenced by the
      interaction between parental lineages. In addition to revealing nonadditive
      genetic effects on female caste determination in a multiple-queen ant species,
      this study reveals strong genetic compatibility effects between parental genomes
      on caste allocation components.

PMID- 21967432
TI  - Predation-imposed selection on threespine stickleback (Gasterosteus aculeatus)
      morphology: a test of the refuge use hypothesis.
AB  - The transition from marine to freshwater life in the threespine stickleback
      (Gasterosteus aculeatus) is accompanied by complex morphological changes
      including reduction in bony armor and change in body shape-but experimental
      evidence for the selective agents behind these evolutionary transitions is
      sparse. We investigated whether selection by predatory fish affects threespine
      stickleback morphology differentially when refuge is absent (pelagic lifestyle
      ancestral condition) or present (benthic lifestyle-derived condition). Our
      results show that selection favors low numbers of lateral plates in habitats with
      refuge, whereas fully plated individuals have a selective advantage in habitats
      without refuge. We also found that a decrease in the length of the caudal
      peduncle increased survival probability, irrespective of habitat. The effect of
      spine lengths on survival was evident only in a multivariate analysis of
      selection, implying that it is essential to account for phenotypic and genetic
      correlations between traits before drawing conclusions about the effects of
      selection on single traits. Apart from uncovering targets and patterns of
      predator-induced selection on threespine stickleback morphology, our results
      provide direct evidence to support the hypothesis that differences in
      antipredator strategies in pelagic versus benthic sticklebacks could play a role
      in the repeated, independent cases of plate number reduction following freshwater
      colonization in this species.

PMID- 21967433
TI  - Comparative analyses of effective population size within and among species: ranid
      frogs as a case study.
AB  - It has recently become practicable to estimate the effective sizes (N(e) ) of
      multiple populations within species. Such efforts are valuable for estimating
      N(e) in evolutionary modeling and conservation planning. We used microsatellite
      loci to estimate N(e) of 90 populations of four ranid frog species (20-26
      populations per species, mean n per population = 29). Our objectives were to
      determine typical values of N(e) for populations of each species, compare N(e)
      estimates among the species, and test for correlations between several geographic
      variables and N(e) within species. We used single-sample linkage disequilibrium
      (LD), approximate Bayesian computation (ABC), and sibship assignment (SA) methods
      to estimate contemporary N(e) for each population. Three of the species-Rana
      pretiosa, R. luteiventris, and R. cascadae- have consistently small effective
      population sizes (<50). N(e) in Lithobates pipiens spans a wider range, with some
      values in the hundreds or thousands. There is a strong east-to-west trend of
      decreasing N(e) in L. pipiens. The smaller effective sizes of western populations
      of this species may be related to habitat fragmentation and population
      bottlenecking.

PMID- 21967434
TI  - Evaluating the targets of selection during character displacement.
AB  - Ecological character displacement occurs when competition imposes divergent
      selection on interacting species, causing divergence in traits associated with
      resource use. Generally, divergence is assumed to occur when selection acts on
      the same, continuously varying trait in both species. However, selection might
      target multiple traits, and even closely related heterospecifics involved in
      character displacement might differ in selective targets. We investigated the
      targets of selection in a species of spadefoot toad, Spea multiplicata, during
      experimentally imposed competition with a congener, S. bombifrons. When examining
      traits separately, we found significant selection acting on multiple resource
      acquisition traits. Yet, controlling for the independent effects of these traits
      in a multiple regression revealed that direct selection on a single trait might
      have contributed toward indirect selection on other correlated traits. Moreover,
      although we found evidence for plasticity in most traits, competition with S.
      bombifrons imposed selection on morphology and not on plasticity. Additional
      experiments suggest that the selective targets during character displacement
      might differ between the two species involved in this one instance of character
      displacement. Identifying the targets of competitively mediated selection is
      crucial, because whether and how character displacement ultimately unfolds
      depends on the nature of these targets and correlations among them.

PMID- 21967435
TI  - Nuclear-cytoplasmic interactions reduce male fertility in hybrids of Arabidopsis
      lyrata subspecies.
AB  - We examined the level of postzygotic reproductive isolation in F(1) and F(2)
      hybrids of reciprocal crosses between the Arabidopsis lyrata subspecies lyrata
      (North American) and petraea (European). Our main results are: first, the
      percentage of fertile pollen was significantly reduced in the F(1) and F(2)
      compared to the parental populations. Second, mean pollen fertility differed
      markedly between reciprocal crosses: 84% in the F(2) with ssp. lyrata cytoplasm
      and 61% in the F(2) with ssp. petraea cytoplasm. Third, 17% of the F(2) with ssp.
      petraea cytoplasm showed male sterility (produced less than 30 pollen grains in
      our subsample). The hybrids were female fertile. We used QTL mapping to find the
      genomic regions that determine pollen fertility and that restore cytoplasmic male
      sterility (CMS). In the F(2) with ssp. lyrata cytoplasm, an epistatic pair of
      QTLs was detected. In the reciprocal F(2) progeny, four QTLs demonstrated within
      population polymorphism for hybrid male sterility. In addition, in the F(2) with
      ssp. petraea cytoplasm, there was a strong male fertility restorer locus on
      chromosome 2 where a cluster of CMS restorer gene-related PPR genes have been
      found in A. lyrata. Our results underline the importance of cytonuclear
      interactions in understanding genetics of the early stages of speciation.

PMID- 21967436
TI  - Lineage diversification and morphological evolution in a large-scale continental
      radiation: the neotropical ovenbirds and woodcreepers (aves: Furnariidae).
AB  - Patterns of diversification in species-rich clades provide insight into the
      processes that generate biological diversity. We tested different models of
      lineage and phenotypic diversification in an exceptional continental radiation,
      the ovenbird family Furnariidae, using the most complete species-level
      phylogenetic hypothesis produced to date for a major avian clade (97% of 293
      species). We found that the Furnariidae exhibit nearly constant rates of lineage
      accumulation but show evidence of constrained morphological evolution. This
      pattern of sustained high rates of speciation despite limitations on phenotypic
      evolution contrasts with the results of most previous studies of evolutionary
      radiations, which have found a pattern of decelerating diversity-dependent
      lineage accumulation coupled with decelerating or constrained phenotypic
      evolution. Our results suggest that lineage accumulation in tropical continental
      radiations may not be as limited by ecological opportunities as in temperate or
      island radiations. More studies examining patterns of both lineage and phenotypic
      diversification are needed to understand the often complex tempo and mode of
      evolutionary radiations on continents.

PMID- 21967437
TI  - Experimental evolution of RNA versus DNA viruses.
AB  - Based on their extremely high mutation rates, RNA viruses have been traditionally
      considered as the fastest evolving entities in nature. However, recent work has
      revealed that, despite their greater replication fidelity, single-stranded (ss)
      DNA viruses can evolve fast in a similar way. To further investigate this issue,
      we have compared the rates of adaptation and molecular evolution of ssRNA and
      ssDNA viruses under highly controlled laboratory conditions using the
      bacteriophages PhiX174, G4, f1, Qbeta, SP, and MS2 as model systems. Our results
      indicate that ssRNA phages evolve faster than ssDNA phages under strong selective
      pressure, and that their extremely high mutation rates appear to be optimal for
      this kind of scenario. However, their performance becomes similar to that of
      ssDNA phages over the longer term or when the population is moderately well
      adapted. Interestingly, the roughly 100-fold difference between the mutation
      rates of ssRNA and ssDNA phages yields less than a fivefold difference in
      adaptation and nucleotide substitution rates. The results are therefore
      consistent with the observation that, despite their lower mutation rates, ssDNA
      viruses can sometimes match the evolvability of RNA viruses.

PMID- 21967438
TI  - Food-environment mediates the outcome of specific interactions between a
      bumblebee and its trypanosome parasite.
AB  - Specific host-parasite interactions, where the outcome of exposure to a parasite
      depends upon the genotypic identity of both parties, have implications for
      understanding host-parasite coevolution and patterns of genetic diversity. Thus,
      grasping the extent to which these interactions are mediated by environmental
      changes in a spatially and temporally heterogeneous world is vital. In this
      study, it is shown that the environment can influence specific host-parasite
      interactions in the well-studied system of the bumblebee Bombus terrestris and
      its trypanosome parasite Crithidia bombi. Naturally relevant variation in the
      quality of the food environment formed a three-way interaction with both host and
      parasite identity in determining the outcome of infection, with regard to the
      resistance of the host and the transmission of the parasite. The demonstration of
      such a host-genotype by parasite-genotype by environment interaction (G(H) x G(P)
      x E) shows the importance of considering environmental variation when
      investigating host-parasite interactions. Moreover, such interactions may to some
      extent explain levels of genetic diversity in natural host-parasite systems owing
      to the fact that they will create selection mosaics when environments are
      heterogeneous.

PMID- 21967439
TI  - Are relationships between pollen-ovule ratio and pollen and seed size explained
      by sex allocation?
AB  - Positive correlations between pollen-ovule ratio and seed size, and negative
      correlations between pollen-ovule ratio and pollen grain size have been noted
      frequently in a wide variety of angiosperm taxa. These relationships are commonly
      explained as a consequence of sex allocation on the basis of a simple model
      proposed by Charnov. Indeed, the theoretical expectation from the model has been
      the basis for interest in the empirical pattern. However, the predicted
      relationship is a necessary consequence of the mathematics of the model, which
      therefore has little explanatory power, even though its predictions are
      consistent with empirical results. The evolution of pollen-ovule ratios is likely
      to depend on selective factors affecting mating system, pollen presentation and
      dispensing, patterns of pollen receipt, pollen tube competition, female mate
      choice through embryo abortion, as well as genetic covariances among pollen,
      ovule, and seed size and other reproductive traits. To the extent the empirical
      correlations involving pollen-ovule ratios are interesting, they will need
      explanation in terms of a suite of selective factors. They are not explained
      simply by sex allocation trade-offs.

PMID- 21967440
TI  - Polyandry reduces sperm length variation in social insects.
AB  - Postcopulatory sexual selection, either in the form of sperm competition or
      cryptic female choice, is an important selective force that is thought to have
      generated the enormous variation in sperm morphology observed interspecifically.
      However, the evolutionary significance of intraspecific variation in sperm
      morphology, and the role that postcopulatory sexual selection plays in
      influencing this variation, remains poorly investigated in invertebrates. Here,
      we tested the hypothesis that postcopulatory sexual selection reduces variation
      in sperm morphology, both between and within males, in 27 species of eusocial
      ants and bees. These eusocial species offer an unusual opportunity to assess how
      selection acts on variance in sperm morphology, as haploid males produce clonal,
      haploid sperm that does not experience haploid-diploid conflict. We provide solid
      evidence that males of polyandrous ant and bee species indeed produce less
      variable sperm, indicating that sperm competition selected for sperm of superior
      quality. Our results offer a mechanistic explanation for the evolution of high
      quality sperm and provide comprehensive evidence that sperm morphology of social
      insects is influenced by sexual selection.

PMID- 21967441
TI  - The evolution of postreproductive life span as an insurance against
      indeterminacy.
AB  - Postreproductive life span remains a puzzle for evolutionary biologists. The
      explanation of increased inclusive fitness through parental care after
      reproduction that applies for humans is unrealistic for many species. We propose
      a new selective mechanism, independent of parental care, which relies on the
      hypothesis that postreproductive life span can evolve as an insurance against
      indeterminacy: longer life expectancy reduces the risk of dying by chance before
      the cessation of reproductive activity. We demonstrate numerically that the
      duration of evolved postreproductive life span is indeed expected to increase
      with variability in life span duration. An unprecedented assay of 11 strains of
      the collembola Folsomia candida shows the existence of (1) postreproductive life
      span in the absence of parental care; (2) genetic variability in mean
      postreproductive life span and postreproductive life span variability itself; (3)
      strong genetic correlation between latter traits. This new explanation brings
      along the novel idea that loose canalization of a trait (here, somatic life span)
      can itself act as a selective pressure on other traits.

PMID- 21967442
TI  - Best of both worlds? Association between outcrossing and parasite loads in a
      selfing fish.
AB  - Mixed-mating strategies (i.e., intermediate levels of self-fertilization and
      outcrossing in hermaphrodites) are relatively common in plants and animals, but
      why self-fertilization (selfing) rates vary so much in nature has proved
      difficult to explain. We tested the hypothesis that parasites help maintain mixed
      mating using a partially selfing fish (Kryptolebias marmoratus) as a model. We
      show that outcrossed progeny in the wild are genetically more diverse and less
      susceptible to multiple parasite infections than their selfed counterparts. Given
      that outcrossing in K. marmoratus can only be attained by male-hermaphrodite
      matings, our data provide an explanation for the coexistence of males and
      hermaphrodites in androdioecious species where hermaphrodites are unable to
      outcross among themselves. Moreover, our study provides evidence that parasites
      contribute to maintaining mixed-mating in a natural animal population.

PMID- 21967443
TI  - Wheelchair-mounted accelerometers for measurement of physical activity.
AB  - PURPOSE: To evaluate the validity of a wheelchair frame-mounted accelerometer for
      the assessment of physical activity of wheelchair users. METHOD: Twelve
      collegiate wheelchair basketball players participated in this study. The study
      was conducted in a modern indoor gymnasium at a university in the USA. A
      randomized, crossover experimental design was used to investigate accelerometer
      output, participant heart rate, and distance travelled. Participants performed
      two trials of wheeling at a combination of two different effort levels (light and
      moderate: Prescribed using perceived exertion) and two different modes
      (continuous and stop-go). RESULTS: Accelerometer vector magnitude activity counts
      (VM), heart rate (HR), and distance travelled were significantly different
      between light and moderate effort (p < 0.01). The continuous and stop-go wheeling
      modes were not significantly different (p = 0.37) for VM, but were significantly
      different (p < 0.01) for both HR and distance. Between-trial reliability of all
      data collapsed for the effort and mode combinations were: VM: r = 0.85; HR: r =
      0.86; and distance: r = 0.96. CONCLUSION: A wheelchair frame-mounted
      accelerometer differentiated between perceptually-prescribed low and moderate
      effort levels and may prove to be a valid instrument in the detection of a
      wheelchair users' physical activity. [Box: see text].

PMID- 21967444
TI  - Vitamin d and stage 5 chronic kidney disease: a new paradigm?
AB  - Vitamin D receptor agonists (VDRA) are currently recommended for the treatment of
      secondary hyperparathyroidism in stage 5 CKD. They are considered to be
      contraindicated in the presence of low or normal (for a dialysis patient) levels
      of PTH due to the risk of developing adynamic bone disease, with consequent
      vascular calcification. However, these recommendations are increasingly at odds
      with the epidemiological evidence, which consistently shows a large survival
      advantage for patients treated with low-dose VDRAs, regardless of plasma calcium,
      phosphate, or PTH. A large number of pleiotropic effects of vitamin D have been
      described, including inhibition of renin activity, anti-inflammation, and
      suppression of vascular calcification stimulators and stimulation of vascular
      calcification inhibitors present in the uremic milieu. Laboratory studies suggest
      that a normal cellular vitamin D level is necessary for normal cardiomyocyte and
      vascular smooth muscle function. While pharmacological doses of VDRA can be
      harmful, the present evidence suggests that the level of 1,25
      dihydroxycholecalciferol should also be more physiological in stage 5 CKD, and
      that widespread use of low-dose VDRA would be beneficial. A randomized controlled
      trial to test this hypothesis is warranted.

PMID- 21967446
TI  - Emergence of novel fungal pathogens by ecological speciation: importance of the
      reduced viability of immigrants.
AB  - Expanding global trade and the domestication of ecosystems have greatly
      accelerated the rate of emerging infectious fungal diseases, and host-shift
      speciation appears to be a major route for disease emergence. There is therefore
      an increased interest in identifying the factors that drive the evolution of
      reproductive isolation between populations adapting to different hosts. Here, we
      used genetic markers and cross-inoculations to assess the level of gene flow and
      investigate barriers responsible for reproductive isolation between two sympatric
      populations of Venturia inaequalis, the fungal pathogen causing apple scab
      disease, one of the fungal populations causing a recent emerging disease on
      resistant varieties. Our results showed the maintenance over several years of
      strong and stable differentiation between the two populations in the same
      orchards, suggesting ongoing ecological divergence following a host shift. We
      identified strong selection against immigrants (i.e. host specificity) from
      different host varieties as the strongest and likely most efficient barrier to
      gene flow between local and emerging populations. Cross-variety disease
      transmission events were indeed rare in the field and cross-inoculation tests
      confirmed high host specificity. Because the fungus mates within its host after
      successful infection and because pathogenicity-related loci prevent infection of
      nonhost trees, adaptation to specific hosts may alone maintain both genetic
      differentiation between and adaptive allelic combinations within sympatric
      populations parasitizing different apple varieties, thus acting as a 'magic
      trait'. Additional intrinsic and extrinsic postzygotic barriers might complete
      reproductive isolation and explain why the rare migrants and F1 hybrids detected
      do not lead to pervasive gene flow across years.

PMID- 21967447
TI  - Necrolytic acral erythema in an adolescent.
AB  - In 1996 el Darouti and Abu el Ela described seven Egyptian patients with similar
      cutaneous lesions and proposed necrolytic acral erythema (NAE) as a distinct
      entity of the necrolytic erythema family. Since then, NAE has emerged as a
      cutaneous manifestation of hepatitis C virus infection and taken its place in the
      literature as a marker for systemic disease. NAE initially presents with burning,
      pruritic eruptions of circumscribed, erythematous papules with flaccid
      vesiculation on the acral surfaces universally affecting the dorsum of the feet.
      The presenting papules of acute NAE evolve over time into confluent, velvety,
      hyperkeratotic plaques with decreased central erythema but a characteristic dark
      erythematous rim and adherent scale. Although mostly misdiagnosed as psoriasis or
      inflammatory dermatitis, NAE can be definitively placed among the necrolytic
      erythema family as a distinct entity based on clinical and histopathologic
      characteristics. We report a case of necrolytic acral erythema in a 17-year-old
      followed by a review of the literature.

PMID- 21967448
TI  - Low prevalence of hepatitis A virus infection among autochthonous populations of
      New World non-human primates.

PMID- 21967451
TI  - Spontaneous umbilical cord haematoma and congenital factor VII deficiency.

PMID- 21967452
TI  - Compound nouns in spoken language production by speakers with aphasia compared to
      neurologically healthy speakers: an exploratory study.
AB  - Compounds are words that are made up of at least two other words (lexemes),
      featuring lexical and syntactic characteristics and thus particularly interesting
      for the study of language processing. Most studies of compounds and language
      processing have been based on data from experimental single word production and
      comprehension tasks. To enhance the ecological validity of morphological
      processing research, data from other contexts, such as discourse production, need
      to be considered. This study investigates the production of nominal compounds in
      semi-spontaneous spoken texts by a group of speakers with fluent types of aphasia
      compared to a group of neurologically healthy speakers. The speakers with aphasia
      produce significantly fewer nominal compound types in their texts than the non
      aphasic speakers, and the compounds they produce exhibit fewer different types of
      semantic relations than the compounds produced by the non-aphasic speakers. The
      results are discussed in relation to theories of language processing.

PMID- 21967449
TI  - (Mis)perception of sleep in insomnia: a puzzle and a resolution.
AB  - Insomnia is prevalent, causing severe distress and impairment. This review
      focuses on illuminating the puzzling finding that many insomnia patients
      misperceive their sleep. They overestimate their sleep onset latency (SOL) and
      underestimate their total sleep time (TST), relative to objective measures. This
      tendency is ubiquitous (although not universal). Resolving this puzzle has
      clinical, theoretical, and public health importance. There are implications for
      assessment, definition, and treatment. Moreover, solving the puzzle creates an
      opportunity for real-world applications of theories from clinical, perceptual,
      and social psychology as well as neuroscience. Herein we evaluate 13 possible
      resolutions to the puzzle. Specifically, we consider the possible contribution,
      to misperception, of (1) features inherent to the context of sleep (e.g.,
      darkness); (2) the definition of sleep onset, which may lack sensitivity for
      insomnia patients; (3) insomnia being an exaggerated sleep complaint; (4)
      psychological distress causing magnification; (5) a deficit in time estimation
      ability; (6) sleep being misperceived as wake; (7) worry and selective attention
      toward sleep-related threats; (8) a memory bias influenced by current symptoms
      and emotions, a confirmation bias/belief bias, or a recall bias linked to the
      intensity/recency of symptoms; (9) heightened physiological arousal; (10)
      elevated cortical arousal; (11) the presence of brief awakenings; (12) a fault in
      neuronal circuitry; and (13) there being 2 insomnia subtypes (one with and one
      without misperception). The best supported resolutions were misperception of
      sleep as wake, worry, and brief awakenings. A deficit in time estimation ability
      was not supported. We conclude by proposing several integrative solutions.

PMID- 21967453
TI  - Left atrial dysfunction is a predictor of postcoronary artery bypass atrial
      fibrillation: association of left atrial strain and strain rate assessed by
      speckle tracking.
AB  - BACKGROUND: Even though atrial fibrillation (AF) is the most common arrhythmia
      after coronary artery bypass grafting (CABG), its etiology remains poorly
      understood. Several factors are linked to postoperative AF (POAF), including
      advanced age and systemic inflammation. However, left atrial (LA) contractile
      dysfunction has not been evaluated in the perioperative scenario. AIM: To
      evaluate LA function through strain and strain rate in patients with coronary
      artery disease undergoing CABG and its correlation with POAF. METHODS: We studied
      70 patients undergoing CABG in sinus rhythm at the time of surgery. Preoperative
      echocardiography with evaluation of LA strain and strain rate by speckle tracking
      was performed. The occurrence of POAF was evaluated by continuous monitoring.
      Baseline and postoperative C-reactive protein (CRP) levels were measured to
      evaluate systemic inflammation. RESULTS: After 1-week follow-up 26% of subjects
      developed AF. LA strain s wave (LASs) and LA strain rate s (LASRs) and a wave
      (LASRa) were significantly decreased in patients who developed POAF: LASs (10 +/-
      1% vs. 24 +/- 1%, P < 0.001), LASRs (0.6 +/- 0.1 sec(-1) vs. 1.2 +/- 0.1 sec(-1)
      , P < 0.001), LASRa (-0.6 +/- 0.1 sec(-1) vs. -1.8 +/- 0.1 sec(-1) , P < 0.001).
      LASRs, LASRa, age, and LA volume were independent predictors of POAF. CRP at
      baseline was similar irrespective of POAF development. CONCLUSIONS: LA
      dysfunction, evaluated by strain and strain rate is an independent predictor of
      POAF and contributes to classic risk factors like age and atrial volume.

PMID- 21967454
TI  - Evaluating the anti-fertility potential of alpha-chlorohydrin on testis and
      spermatozoa in the adult male wild Indian house rat (Rattus rattus).
AB  - To examine the effects of alpha-chlorohydrin on testis and cauda epididymis in
      the male house rat (Rattus rattus), 24 adult male rats were segregated into two
      groups. Group I rats were force-fed daily by intragastric intubation with alpha
      chlorohydrin at a single dose of 1.0 mg/100 g body weight/d for 5, 15, and 45
      days. Another group was fed with distilled water, which served as the control.
      The treated male rats were paired with 24 adult proestrus female rats for 5 days
      after the last oral treatment and fertility was tested. At the end of the
      experiments, all of the male rats were weighed and killed by cervical
      dislocation. The right testes were removed, weighed, and processed for
      ultrastructural changes of spermatozoa from the cauda epididymis and testis under
      scanning electron microscopy (SEM) and transmission electron microscopy (TEM).
      The seminiferous tubular area, nuclear diameter of the Sertoli and Leydig cells,
      percentage of spermatogonia, primary spermatocytes, secondary spermatocytes,
      spermatids, spermatozoa, and Sertoli cells in each group were compared
      morphometrically. Our results showed that the percentages of primary
      spermatocytes steadily increased from 5 to 15 days, but primary and secondary
      spermatocytes decreased significantly at 45 days. There was a steady decline in
      the percentages of spermatozoa and spermatids at all fixation intervals in the
      treated animals, but the percentages of spermatogonia and Sertoli cells increased
      significantly at 15 and 45 days. Seminiferous tubular areas, nuclear diameter of
      Leydig and Sertoli cells, and fertility rates were reduced after 45 days of
      treatment. SEM and TEM studies revealed severe morphological abnormalities in the
      spermatozoa, including deglutination of the acrosomal part, loss of head
      capsules, and fragmentation of tail fibrils. There was an enhanced anti-fertility
      effect and a lower number of implantation sites in the rats treated for 5 days.
      Our results validate alpha-chlorohydrin as a successful anti-fertility agent that
      prevents spermatogenesis.

PMID- 21967455
TI  - In vitro 14C-labeled amino acid uptake changes and surface abnormalities in the
      colon after 1,2-dimethylhydrazine-induced experimental carcinogenesis: protection
      by zinc.
AB  - The present study explored the regulatory role of zinc on the in vitro uptake of
      14C-glucose and 14C-labeled amino acids and on colonic surface abnormalities
      after 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis. Rats were
      segregated into four groups: control, DMH-treated, zinc-treated, and DMH + zinc
      treated. Colon carcinogenesis was induced through weekly subcutaneous injections
      of DMH (30 mg/kg body weight) for 16 weeks. Zinc (in the form of zinc sulfate)
      was given to rats at a dose level of 227 mg/L in their drinking water. DMH
      treatment caused a significant decrease in the activities of disaccharidases
      (sucrase, lactase, and maltase), but a significant increase in the activity of
      alkaline phosphatase. In vitro uptake of 14C-D-glucose and the amino acids 14C
      glycine, 14C-alanine, 14C-lysine, and 14C-leucine were significantly higher in
      the colons of DMH-treated rats. Zinc supplementation of DMH-treated rats resulted
      in regulating the altered intestinal enzyme activities and in vitro uptake of 14C
      amino acids and 14C-glucose. Scanning electron microscopy revealed drastic
      alterations in the colon surface morphology after DMH treatment, which were
      restored after zinc supplementation. Our results confirm a beneficial effect of
      zinc against DMH-induced alterations in the colons of rats.

PMID- 21967450
TI  - Pain, nicotine, and smoking: research findings and mechanistic considerations.
AB  - Tobacco addiction and chronic pain represent 2 highly prevalent and comorbid
      conditions that engender substantial burdens upon individuals and systems.
      Interrelations between pain and smoking have been of clinical and empirical
      interest for decades, and research in this area has increased dramatically over
      the past 5 years. We conceptualize the interaction of pain and smoking as a
      prototypical example of the biopsychosocial model. Accordingly, we extrapolated
      from behavioral, cognitive, affective, biomedical, and social perspectives to
      propose causal mechanisms that may contribute to the observed comorbidity between
      these 2 conditions. The extant literature was 1st dichotomized into
      investigations of either effects of smoking on pain or effects of pain on
      smoking. We then integrated these findings to present a reciprocal model of pain
      and smoking that is hypothesized to interact in the manner of a positive feedback
      loop, resulting in greater pain and increased smoking. Finally, we proposed
      directions for future research and discussed clinical implications for smokers
      with comorbid pain disorders. We observed modest evidence that smoking may be a
      risk factor in the multifactorial etiology of some chronically painful conditions
      and that pain may come to serve as a potent motivator of smoking. We also found
      that whereas animal studies yielded consistent support for direct pain-inhibitory
      effects of nicotine and tobacco, results from human studies were much less
      consistent. Future research in the emerging area of pain and smoking has the
      potential to inform theoretical and clinical applications with respect to tobacco
      smoking, chronic pain, and their comorbid presentation. (PsycINFO Database Record
      (c) 2011 APA, all rights reserved).

PMID- 21967456
TI  - Vinblastine-induced cytogenotoxicity in spermatogonia and its transmission in the
      germline cells of Swiss mice.
AB  - Vinblastine, a cytotoxic anti-neoplastic drug and a known mitotic spindle
      inhibitor, has reportedly induced numerical and structural alterations in
      chromosome complements of treated animals. In the present study, cytogenotoxic
      effects of three different doses of vinblastine (0.5, 1.0, and 1.5 mg/kg body
      weight) were assessed from mouse spermatogonia at 24 hours after treatment after
      a single intraperitoneal exposure. The transmission potential of such effects in
      the male germline of mice was also assessed from primary spermatocytic chromosome
      analysis and sperm morphology assay at weeks 4 and 8 after treatments,
      respectively. Induction of statistically significant percentages of aberrant
      spermatogonial metaphases (P <= 0.01) and chromosomal aberrations (excluding
      gaps) (P <= 0.05) in vinblastine-treated mice indicated its clastogenicity.
      Induction of significant percentages of aberrant primary spermatocytes with
      atypical bivalents (P <= 0.01) and different categories of abnormal sperm,
      although not with significant variation in frequency, indicated the transmission
      of vinblastine-induced cytogenotoxic effects from spermatogonia to spermatocyte
      to sperm. We conclude that vinblastine is cytogenotoxic to mouse spermatogonia
      and that such induced effects are transmissible in the male germline cells of
      Swiss mice. Potential transmission of such cytogenotoxic effects, from cancer
      survivors of reproductive age with vinblastine pretreatment through gametes, is a
      serious concern.

PMID- 21967457
TI  - Studies on anti-metastatic and anti-invasive effects of harmine using highly
      metastatic murine B16F-10 melanoma cells.
AB  - Harmine is a beta-carboline alkaloid from the plant Peganum harmala. We evaluated
      the anti-metastatic activity of harmine using in vivo mouse lung metastasis and
      in vitro models. Lung metastasis was induced using B16F-10 melanoma cells in
      C57BL/6 mice by three different modalities of administration: simultaneous,
      prophylactic, and after tumor development. Harmine significantly inhibited tumor
      nodule formation in the lung tissue and decreased various biochemical parameters
      associated with lung metastasis. Higher expression levels of pro-metastatic genes
      such as matrix metalloproteinase-9 (MMP-9), extracellular signal[en]regulated
      kinase (ERK), and vascular endothelial factors (VEGFs), all of which play
      important roles in cancer cell migration and invasion, were observed in the
      metastatic group compared with normal, but were all down-regulated by treatment
      with harmine. Harmine was also able to inhibit tumor cell proliferation,
      invasion, and migration in vitro. In conclusion, harmine exerts anti-metastatic
      activity and this effect could be linked to the metastasis-related signaling
      pathway that includes ERK, VEGF, and MMPs.

PMID- 21967458
TI  - Vernolide-A inhibits radiation-induced hypoxia-mediated tumor angiogenesis by
      regulating HIF-1alpha, MMP-2, MMP-9, and VEGF.
AB  - We investigated the effect of vernolide-A on the inhibition of radiation-induced
      tumor angiogenesis in C57BL/6 mice. Vernolide-A administration significantly
      reduced the tumor volume of radiation-exposed mice. Serum vascular endothelial
      growth factor (VEGF) levels were drastically elevated during tumor progression
      and irradiation and were significantly reduced by treatment with vernolide-A.
      Immunohistochemical analysis also revealed reduced vascular density after
      treatment with vernolide-A, and 3H-thymidine incorporation assay and soft agar
      assay showed that vernolide-A could inhibit the proliferation of B16F-10 melanoma
      cells in vitro along with radiation. Vernolide-A also caused a significant
      inhibition in the invasion of irradiated B16F-10 melanoma cells across the
      collagen matrix, and inhibited the radiation-induced gene expression of hypoxia
      inducible transcription factor-1alpha (HIF-1alpha) and VEGF in B16F-10 cells and
      VEGF receptor (Flk-1) expression in human umbilical vein endothelial cells.
      Gelatin zymographic analysis showed that vernolide-A could also inhibit the
      radiation-induced activation of matrix metalloproteinases (MMPs). Our results
      indicate that vernolide-A inhibits radiation-induced tumor angiogenesis by
      regulating HIF-1alpha, MMP-2, MMP-9, and VEGF.

PMID- 21967459
TI  - Radioprotective role of selenium after single-dose radioiodine (131I) exposure to
      red blood cells of rats.
AB  - The present study elucidated the protective potential of selenium following 131I
      induced alterations in rat blood. Forty rats were segregated into 4 groups.
      Animals in Group I served as normal controls, Group II animals were injected with
      a single dose of 3.7 Mbq of 131I (carrier free), Group III animals were
      supplemented with selenium (1 ppm), and Group IV animals were given a combined
      treatment of selenium and 131I. 131I treatment of rats showed significant
      increases in total leukocyte counts (TLCs), lymphocytes, and neutrophils
      (monocytes and eosinophils were not recorded). These were significantly restored
      upon supplementation of selenium. Lipid peroxidase (LPO), glutathione peroxidase
      (GSH-PX), reduced glutathione (GSH), superoxide dismutase (SOD), and delta
      aminolevulinic acid dehydratase (delta-ALAD) were found to be enhanced following
      131I treatment. However, the levels of catalase were found to be decreased.
      Selenium administration to 131I-treated rats resulted in significant restoration
      of these enzyme activities. Scanning electron microscope (SEM) studies also
      revealed various surface deformities in erythrocytes after 131I treatment, which
      upon supplementation with selenium were significantly restored. In conclusion,
      selenium may prove to be an effective radioprotector following 131I treatment.

PMID- 21967460
TI  - Ipobscurine, an indole alkaloid from Ipomoea obscura, inhibits tumor cell
      invasion and experimental metastasis by inducing apoptosis.
AB  - In the present study, we demonstrate that ipobscurine, an indole alkaloid
      fraction isolated from Ipomoea obscura, can reduce the formation of B16F-10
      melanoma-induced metastatic nodules and inhibit the proliferation, migration, and
      invasion of B16F-10 melanoma cells in vitro, possibly by inhibiting pro
      metastatic genes such as matrix metalloproteinases (MMPs) and inflammatory
      mediators such as cyclooxygenase-2 (COX-2), inducible nitric oxide synthase
      (iNOS), and pro-inflammatory cytokines. Ipobscurine may also promote apoptosis by
      up-regulating pro-apoptotic molecules such as caspase-3, p53, and Bax and by down
      regulating anti-apoptotic Bcl-2. In addition, we have observed that ipobscurine
      suppresses various transcription factors such as nuclear factor-kappaB (NF
      kappaB) and activator protein, which are possibly associated with the suppression
      of apoptosis in cancer cells. Ipobscurine has also been shown to inhibit cell
      growth with arrest at G1 and reduce transition to the S and G2/M phases of the
      cell cycle.

PMID- 21967461
TI  - Effect of PLGA hydrophilia on the drug release and the hypoglucemic activity of
      different insulin-loaded PLGA microspheres.
AB  - The effects of viscosity and hydrophilic characteristics of different PLGA
      polymers on the microencapsulation of insulin have been studied in vitro and in
      vivo after subcutaneous administration to hyperglycemic rats. Hydrophilic PLGA
      polymers produced a higher burst effect than the hydrophobic ones. Moreover, an
      incomplete insulin release was observed with the hydrophilic PLGA polymers in
      comparison with the hydrophobic ones. An explanation for that incomplete release
      can be the development of polymer-insulin interactions associated to the polymer
      hydrophilic/hydrophobic character, as detected by DSC analysis. Differences in
      the release rate of microsphere formulations lead to differences in the
      hypoglycemic action and the weight of animals. Hydrophobic PLGA was able to
      prolong the hypoglycemic action up to 4 weeks which is at least double than that
      obtained with hydrophilic PLGA of a similar viscosity. Comparing insulin
      microspheres with an immediate release formulation, microspheres can increase
      insulin relative bioavailability up to four times.

PMID- 21967462
TI  - Nano self-assemblies based on cholate grafted poly-L-lysine enhanced the
      solubility of sterol-like drugs.
AB  - The physicochemical compatibility between amphiphilic polymers and hydrophobic
      drugs has been recognized as an important issue for improving the drug
      solubilisation in polymeric micelle formulations. In this work, poly-L-lysine
      (PLL) grafted by cholate pendants as the only hydrophobic moiety were synthesized
      in order to facilitate the solubilisation of sterol drugs. Results showed that
      micelles formed by cholate grafted PLL encapsulated significantly higher level of
      prednisolone and estradiol than palmitoylated PLL micelles, whereas the
      solubilisation capacity of non-sterol drug (griseofulvin) is inefficient for both
      polymers. This suggests that higher drug-polymer incorporation can be achieved by
      the inclusion of hydrophobic moieties with similar architecture as the drugs,
      i.e. 'drug-like' functional groups, which will be useful for the future design of
      colloidal systems for the encapsulation of specific drug.

PMID- 21967463
TI  - Formulation of sustained-release microspheres of granulocyte macrophage colony
      stimulating factor by freezing-induced phase separation with dextran and
      encapsulation with blended polymers.
AB  - This study aimed to assess the potential merits of formulating sustained-release
      microspheres of recombinant human granulocyte macrophage colony stimulating
      factor (rhGM-CSF) via freezing-induced phase separation (FIPS) of the protein
      with dextran followed by encapsulation with binary mixture of poly(lactic-co
      glycolic acid) (PLGA) 2A (MW~12K) and 3A (MW~47K) or of PLGA2A and polylactic
      acid (PLA; MW~83K). The formulated dextran particles and microspheres were
      characterized in vitro for loading, aggregation, bioactivity and release behavior
      of the protein where appropriate. rhGM-CSF retained about 60% of bioactivity with
      no significant aggregation after each formulation step. Encapsulation of protein
      loaded dextran particles attained only 80% with the PLGA2A and PLGA3A blend, but
      100% with the PLGA2A and PLA mixture. The former formulation exhibited a
      triphasic in-vitro release profile typical of PLGA microspheres while the latter
      revealed a much lower initial burst followed by a steady and complete release of
      rhGM-CSF with preserved bioactivity over a 15-day period.

PMID- 21967464
TI  - Phonon engineering in carbon nanotubes by controlling defect concentration.
AB  - Outstanding thermal transport properties of carbon nanotubes (CNTs) qualify them
      as possible candidates to be used as thermal management units in electronic
      devices. However, significant variations in the thermal conductivity (kappa)
      measurements of individual CNTs restrict their utilizations for this purpose. In
      order to address the possible sources of this large deviation and to propose a
      route to solve this discrepancy, we systematically investigate the effects of
      varying concentrations of randomly distributed multiple defects (single and
      double vacancies, Stone-Wales defects) on the phonon transport properties of
      armchair and zigzag CNTs with lengths ranging between a few hundred nanometers to
      several micrometers, using both nonequilibrium molecular dynamics and atomistic
      Green's function methods. Our results show that, for both armchair and zigzag
      CNTs, kappa converges nearly to the same values with different types of defects,
      at all lengths considered in this study. On the basis of the detailed mean free
      path analysis, this behavior is explained with the fact that intermediate and
      high frequency phonons are filtered out by defect scattering, while low frequency
      phonons are transmitted quasi-ballistically even for several micrometer long
      CNTs. Furthermore, an analysis of variances in kappa for different defect
      concentrations indicates that defect scattering at low defect concentrations
      could be the source of large experimental variances, and by taking advantage of
      the possibility to create a controlled concentration of defects by electron or
      ion irradiation, it is possible to standardize kappa with minimizing the
      variance. Our results imply the possibility of phonon engineering in
      nanostructured graphene based materials by controlling the defect concentration.

PMID- 21967465
TI  - Mechanism-based chemical understanding of chiral symmetry breaking in the Soai
      reaction. A combined probabilistic and deterministic description of chemical
      reactions.
AB  - The experimentally observed distribution of enantiomers in the Soai reaction is
      interpreted in this Article on the basis of a chemical mechanism using a newly
      developed stochastic kinetic method, accelerated Monte Carlo simulation combined
      with deterministic continuation and symmetrization. The method is in principle
      suitable for handling large mechanisms with realistic particle numbers and could
      be useful for any case where the kinetics of a process shows inherent random
      fluctuations. The mechanism shows how a slow initial reaction combined with
      efficient and highly enantioselective autocatalysis can give rise to chiral
      symmetry breaking under completely nonchiral external conditions.

PMID- 21967466
TI  - Infant epidermal skin physiology: adaptation after birth.
AB  - BACKGROUND: Functional and structural skin adaptation is a dynamic process which
      starts immediately after birth in humans and in mammalian skin in general. This
      adjustment to the extrauterine dry environment is accomplished in the first year
      of postnatal life of humans. OBJECTIVES: To assess the dynamic changes in vivo
      after birth in the molecular composition and skin physiology parameters compared
      with older children and adults. METHODS: The molecular composition of the stratum
      corneum (SC) and the water profile were investigated noninvasively by in vivo
      Raman confocal microscopy as a function of depth. Functional parameters including
      transepidermal water loss (characterizing epidermal permeability barrier),
      capacitance (as an indirect parameter for SC hydration) and skin surface pH were
      assessed noninvasively. The measurements were performed in 108 subjects divided
      into six age groups: full-term newborns (1-15 days), babies aged 5-6 weeks,
      babies aged 6+/-1 months, children aged 1-2 years, children aged 4-5 years and
      adults aged 20-35 years. RESULTS: We showed that skin acidification is still
      under development during the first weeks of life. While the basal epidermal
      barrier is competent immediately after birth, the SC is less hydrated in the
      first 2 weeks of postnatal life. Similar continuous decreasing water content
      towards the surface for all age groups was observed, whereas this gradient was
      lower for the newborns. Dynamic changes in the amounts of the natural
      moisturizing factor constituents were revealed in the period of infancy.
      CONCLUSIONS: We demonstrated the relation of formation of an acidic pH as well as
      underlying mechanisms in the induction of a fully hydrated SC over the first
      weeks of human life as a dynamic functional adaptation.

PMID- 21967467
TI  - Effects of formulation parameters on encapsulation efficiency and release
      behavior of thienorphine loaded PLGA microspheres.
AB  - To develop a long-acting injectable thienorphine biodegradable poly (d, l-lactide
      co-glycolide) (PLGA) microsphere for the therapy of opioid addiction, the effects
      of formulation parameters on encapsulation efficiency and release behavior were
      studied. The thienorphine loaded PLGA microspheres were prepared by o/w solvent
      evaporation method and characterized by HPLC, SEM, laser particle size analysis,
      residual solvent content and sterility testing. The microspheres were sterilized
      by gamma irradiation (2.5 kGy). The results indicated that the morphology of the
      thienorphine PLGA microspheres presented a spherical shape with smooth surface,
      the particle size was distributed from 30.19 +/- 1.17 to 59.15 +/- 0.67 MUm and
      the drug encapsulation efficiency was influenced by drug/polymer ratio,
      homogeneous rotation speed, PVA concentration in the water phase and the polymer
      concentration in the oil phase. These changes were also reflected in drug
      release. The plasma drug concentration vs. time profiles were relatively smooth
      for about 25 days after injection of the thienorphine loaded PLGA microspheres to
      beagle dogs. In vitro and in vivo correlation was established.

PMID- 21967468
TI  - Determination of hepatitis C virus genotypes in pruritus patients in saudi
      arabia.
AB  - The main objective of this study was to estimate the prevalence of Hepatitis C
      virus (HCV) genotypes in 56 pruritus patients and 50 healthy blood donors on the
      basis of clinical and laboratory investigations. Both demographic and clinical
      data were collected from each subject after obtaining informed consent and
      approval from an ethics committee. Ten milliliters of venous blood was collected
      from fasting patients (8-10 h) and serum was used for aspartate transaminase and
      alanine transaminase tests, anti-HCV antibody testing, HCV-RNA polymerase chain
      reaction screening, and genotyping analysis. HCV was found to be significantly
      predominant over HBV infection among the pruritus patients (p<0.001). Twelve
      pruritus patients (21.42%) were positive for anti-HCV antibodies and nine of them
      were confirmed positive for HCV RNA presence. Of the two major genotypes
      revealed, genotype 4 was found to be significantly predominant over the mixed
      genotype, that is, 4a/c+3a (p<0.001). Subtyping results showed that a significant
      majority of the type 4 were of the HCV subtype 4a (five patients), followed by 4c
      (two patients) and 4b genotypes (one patient) and mixed genotype 4a/c+3a (one
      patient). Results of this prospective study indicated the significant association
      between pruritus and HCV infection. HCV genotype 4 is the most predominant
      genotype among the pruritus patients and warrants larger studies in different
      ethnicities to find the molecular association between HCV genetic variants and
      pruritus.

PMID- 21967469
TI  - Terra firma-forme dermatosis: a retrospective review of 31 patients.
AB  - Terra firma-forme dermatosis is an idiopathic condition characterized by
      acquired, dirtlike plaques despite normal hygiene. A diagnosis can be reached by
      removing lesions with gentle alcohol swabbing. Although Terra firma-forme
      dermatosis was first described more than 20 years ago and is thought to be not
      uncommon in clinical practice, it has never been systematically studied. There
      are few publications about this condition, including no case series of more than
      six patients. In particular, little is known about the incidence, peak age
      groups, and most common locations of Terra firma-forme dermatosis. A
      retrospective review was conducted to identify cases of Terra firma-forme
      dermatosis in a single-provider practice consisting of 55% pediatric and 45%
      adult patients. Thirty-one patients with Terra firma-forme dermatosis were
      identified, including 10 who presented with Terra firma-forme dermatosis as their
      primary concern. Only two patients were older than 17 years. The median duration
      of lesions was 4 months. The most common lesion locations were the neck, ankles,
      and face. Before presenting to the dermatology clinic, three patients had
      undergone endocrine evaluations, and four had been prescribed topical
      corticosteroids. Terra firma-forme dermatosis is relatively common and most often
      occurs in children on the neck or posterior malleolus. This series exemplifies
      the importance of recognizing Terra firma-forme dermatosis so as to provide rapid
      relief for patients and avoid unnecessary tests and treatments.

PMID- 21967470
TI  - Toward functioning and usable brain-computer interfaces (BCIs): a literature
      review.
AB  - PURPOSE: The aim of this paper is to provide an exhaustive review of the
      literature about brain-computer interfaces (BCIs) that could be used with these
      paralysed patients. The electroencephalography (EEG) is the best candidate for
      the continuous use in the environment of patients' houses, due to its portability
      and ease of use. For this reason, the present paper will focus on this kind of
      BCI. Moreover, it is our aim to focus more on the patients, regarding their
      active role in the modulation of the brain activity. This leads to a
      differentiation between studies that use an active regulation and studies that
      use a non-active regulation. METHOD: Relevant articles in the BCIs field were
      selected using MEDLINE and PsycINFO. RESULTS: Research through data banks
      produced 980 results, which were reduced to 127 after exclusion criteria
      selection. These references were divided in four categories, based on the use of
      active or non-active regulation, and on the event related potential used.
      CONCLUSIONS: In most of the examined works, the focus was on the development of
      systems and algorithms able to recognise and classify brain events. Although this
      kind of research is fundamental, a user-centred point of view was rarely adopted.
      [Box: see text].

PMID- 21967471
TI  - Evaluation of endothelial function and subclinical atherosclerosis in association
      with hepatitis C virus in HIV-infected patients: a cross-sectional study.
AB  - BACKGROUND: Relationship of hepatitis C virus (HCV) infection with an increased
      risk of cardiovascular disease (CVD) in HIV-infected patients remains
      controversial. We evaluated endothelial function and subclinical atherosclerosis
      in HIV-infected patients with and without HCV. METHODS: Flow-mediated dilatation
      (FMD) of the brachial artery and circulating levels of cell adhesion molecules
      (CAM) were measured in HCV/HIV-coinfected and HIV-monoinfected patients.
      Subclinical atherosclerosis was assessed by carotid intima-media thickness
      (cIMT). RESULTS: 63 (31%) HCV/HIV-coinfected and 138 (69%) HIV-monoinfected
      patients were included. Median soluble vascular CAM-1 (sVCAM-1) and intercellular
      CAM-1 (sICAM-1) levels were significantly higher in HIV/HCV-coinfected patients
      (P < 0.001 for both cases). Median (interquartile range) FMD was 6.21% (2.86
      9.62) in HCV/HIV-coinfected and 5.54% (2.13-9.13) in HIV-monoinfected patients (P
      = 0.37). Adjustment for variables associated with HCV and FMD disclosed similar
      results. FMD correlated inversely with cIMT and age. Carotid IMT did not differ
      between HCV/HIV-coinfected and HIV-monoinfected patients in unadjusted (0.61
      [0.55-0.65] mm vs 0.60 [0.53-0.72] mm; P = 0.39) or adjusted analyses.
      CONCLUSION: HCV infection was associated with higher levels of sICAM-1 and sVCAM
      1, but no evidence of increased subclinical atherosclerosis was found when
      endothelial function was evaluated through FMD, or when assessing the cIMT.

PMID- 21967472
TI  - Method repeatability for measuring Enterococcus in southern California beach
      sands.
AB  - AIMS: A recent study that evaluated 22 methods for enumerating faecal indicator
      bacteria in sand recommended standardization to a preferred method, but all
      researchers involved in that study had extensive experience in processing sand
      samples. The purpose of this study was to evaluate how well the recommended
      method can be transferred to laboratories without such experience. METHODS AND
      RESULTS: Eight southern California laboratories that rarely measure bacteria in
      sand processed six sand and three water samples in replicates to assess
      repeatability. Among-laboratory variability was found to be less than within
      laboratory variability, with no significant differences in results among any of
      the laboratories. Moreover, within-laboratory variability was comparable between
      the sand and water samples, indicating that the elution procedure added little
      additional method error even when performed by laboratories without prior
      experience. CONCLUSIONS: The simple extraction method for enumerating
      Enterococcus in beach sands was easily transferable to and repeatable among
      laboratories with little or no prior experience. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The demonstrated success of technology transfer will further demonstrate
      the success of method standardization and adoption, aiding in understanding of
      how sands affect surface water quality.

PMID- 21967473
TI  - Significance and causes of abnormal preoperative coagulation test results in
      children.
AB  - To prevent bleeding related to adenoidectomy and tonsillectomy, coagulation
      screening tests were, until recently, performed routinely in the Czech Republic
      for all paediatric patients. The aim of this study was to evaluate benefit of
      preoperative coagulation screening tests in children. We retrospectively analysed
      laboratory and clinical data of children referred for abnormal preoperative
      coagulation test results (aPTT, PT) to the outpatient haematology clinic. A total
      of 274 paediatric patients were retrospectively evaluated due to abnormal
      preoperative coagulation tests results. In 140 of 274 patients (51.1%),
      coagulation tests were normal on repeated testing in a specialized haematology
      clinic. Ten patients had decreased factor XII. Five patients had a suspected
      bleeding disorder which was confirmed in two of them. One patient had low levels
      of von Willebrand factor, and one patient had mild factor VII deficiency. Both
      these patients had positive personal and/or family history of bleeding. Each case
      history was taken individually, without use of standardized questionnaires.
      Bleeding complications were not observed, and coagulation factor replacement was
      not needed perioperatively in our cohort. The majority of abnormal findings in
      aPTT and PT appeared only transiently. All the bleeding disorders found in our
      cohort of patients were mild in nature. Our findings provide supportive evidence
      for the current national Czech recommendation: laboratory coagulation screening
      should be performed only in patients with positive family and/or personal
      bleeding history.

PMID- 21967474
TI  - Focal left atrial tachycardias not associated with prior catheter ablation for
      atrial fibrillation: clinical and electrophysiological characteristics.
AB  - BACKGROUND: The clinical features and electrophysiological characteristics of
      patients with focal left atrial tachycardias (LATs) are not well characterized.
      This study reports the experience of a single center in catheter mapping and
      radiofrequency ablation of focal LAT not associated with prior atrial
      fibrillation (AF) ablation, including in cardiac sarcoidosis and transplant
      patients. METHODS: Patients with focal LAT without a history of AF ablation were
      included in this retrospective analysis. RESULTS: A total of 24 focal LATs were
      documented in 20 patients. Two patients were subsequently diagnosed with cardiac
      sarcoidosis. Two patients were status post a thoracic transplant. The mean
      initial cycle length of the focal LATs was 347.4 +/- 96.2 ms (range 190-510 ms).
      Patients with a pulmonary vein (PV) ostium focus (n = 6) demonstrated a shorter
      cycle length than patients with other LA foci (259.2 +/- 56.4 ms vs 371.9 +/-
      91.1 ms, P = 0.02), as well as a trend for a history of AF (67% vs 21%, P = NS).
      Catheter ablation was immediately successful for 19 of 22 focal LATs.
      CONCLUSIONS: Focal LATs not associated with prior AF ablation can originate in a
      variety of LA locations and clinical settings. Focal LAT arising in the PV ostia
      is associated with a history of AF and demonstrates a faster tachycardia rate. We
      also report focal LAT in cardiac sarcoidosis patients and in the donor heart of
      an orthotopic heart transplant recipient. Radiofrequency ablation is a successful
      treatment for focal LAT not associated with prior ablation, including those
      refractory to medical therapy.

PMID- 21967475
TI  - Mapping the "forbidden" transverse-optical phonon in single strained silicon
      (100) nanowire.
AB  - The accurate manipulation of strain in silicon nanowires can unveil new
      fundamental properties and enable novel or enhanced functionalities. To exploit
      these potentialities, it is essential to overcome major challenges at the
      fabrication and characterization levels. With this perspective, we have
      investigated the strain behavior in nanowires fabricated by patterning and
      etching of 15 nm thick tensile strained silicon (100) membranes. To this end, we
      have developed a method to excite the "forbidden" transverse-optical (TO) phonons
      in single tensile strained silicon nanowires using high-resolution polarized
      Raman spectroscopy. Detecting this phonon is critical for precise analysis of
      strain in nanoscale systems. The intensity of the measured Raman spectra is
      analyzed based on three-dimensional field distribution of radial, azimuthal, and
      linear polarizations focused by a high numerical aperture lens. The effects of
      sample geometry on the sensitivity of TO measurement are addressed. A
      significantly higher sensitivity is demonstrated for nanowires as compared to
      thin layers. In-plane and out-of-plane strain profiles in single nanowires are
      obtained through the simultaneous probe of local TO and longitudinal-optical (LO)
      phonons. New insights into strained nanowires mechanical properties are inferred
      from the measured strain profiles.

PMID- 21967476
TI  - The importance of illness perception in end-stage renal disease: associations
      with psychosocial and clinical outcomes.
AB  - Illness perceptions refer to organized beliefs surrounding the symptoms,
      consequences, time course, controllability, and causes of an illness. Illness
      perceptions have been shown to predict a range of psychosocial and clinical
      outcomes in patients with ESRD including depression, nonadherence, and even
      survival. Accordingly, personal illness beliefs are novel yet potentially
      modifiable prognostic factors. Studies are required to assert whether illness
      perception-based interventions deliver the promise of improved subjective and
      clinical well-being in patients with ESRD.

PMID- 21967477
TI  - Horizontal transmission of Rickettsia felis between cat fleas, Ctenocephalides
      felis.
AB  - Rickettsia felis is a rickettsial pathogen primarily associated with the cat
      flea, Ctenocephalides felis. Although laboratory studies have confirmed that R.
      felis is maintained by transstadial and transovarial transmission in C. felis,
      distinct mechanisms of horizontal transmission of R. felis among cat fleas are
      undefined. Based on the inefficient vertical transmission of R. felis by cat
      fleas and the detection of R. felis in a variety of haematophagous arthropods, we
      hypothesize that R. felis is horizontally transmitted between cat fleas. Towards
      testing this hypothesis, flea transmission of R. felis via a bloodmeal was
      assessed weekly for 4 weeks. Rhodamine B was used to distinguish uninfected
      recipient and R. felis-infected donor fleas in a rickettsial horizontal
      transmission bioassay, and quantitative real-time PCR assay was used to measure
      transmission frequency; immunofluorescence assay also confirmed transmission.
      Female fleas acquired R. felis infection more readily than male fleas after
      feeding on a R. felis-infected bloodmeal for 24 h (69.3% and 43.3%, respectively)
      and both Rickettsia-uninfected recipient male and female fleas became infected
      with R. felis after cofeeding with R. felis-infected donor fleas (3.3-40.0%).
      Distinct bioassays were developed to further determine that R. felis was
      transmitted from R. felis-infected to uninfected fleas during cofeeding and
      copulation. Vertical transmission of R. felis by infected fleas was not
      demonstrated in this study. The demonstration of horizontal transmission of R.
      felis between cat fleas has broad implications for the ecology of R. felis
      rickettsiosis.

PMID- 21967478
TI  - Preoxidation for colorimetric sensor array detection of VOCs.
AB  - A disposable preoxidation technique that dramatically improves the detection and
      identification of volatile organic compounds (VOCs) by a colorimetric sensor
      array is reported. Passing a vapor stream through a tube packed with chromic acid
      on silica immediately before the colorimetric sensor array substantially
      increases the sensitivity to less-reactive VOCs and improves the limits of
      detection (LODs) ~300-fold, permitting the detection, identification, and
      discrimination of 20 commonly found indoor VOC pollutants at both their
      immediately dangerous to life or health (IDLH) and permissible exposure limit
      (PEL) concentrations. The LODs of these pollutants were on average 1.4% of their
      respective PELs.

PMID- 21967479
TI  - A Spanish pilot investigation for a crosslinguistic study in protracted
      phonological development.
AB  - A crosslinguistic study is underway concerning children's protracted phonological
      development (i.e. speech sound disorders). The current article reports pilot
      Spanish data for this study from two 4-year-old boys with protracted phonological
      development. The purposes of the pilot study were to: (1) develop and evaluate a
      word list for elicitation that could be used across Spanish dialects and that
      sufficiently sampled Spanish word lengths, stress patterns, word shapes and
      phonemes; and (2) to derive hypotheses for the larger study, based on patterns
      found in these children's speech, and a review of the literature. The two
      speakers showed some developmental patterns reported for other languages (e.g.
      constraints on production of liquids and word-initial consonants in unstressed
      syllables) but also patterns that may reflect Spanish phonological inventories,
      allophony and frequencies. These data helped consolidate the Spanish word list
      for elicitation and led to questions for the ongoing study concerning word
      structure, multisyllabic words, liquids, fricatives and vowel sequences.

PMID- 21967480
TI  - Assessment of right ventricular function using echocardiographic speckle tracking
      of the tricuspid annular motion: comparison with cardiac magnetic resonance.
AB  - BACKGROUND: Assessment of right ventricular (RV) function is difficult due to the
      complex shape of this chamber. Tricuspid annular plane systolic excursion (TAPSE)
      measured with M-mode echocardiography is frequently used as an index of RV
      function. However, its accuracy may be limited by ultrasound beam misalignment.
      We hypothesized that two-dimensional (2D) speckle tracking echocardiography (STE)
      could provide more accurate estimates of RV function. Accordingly, STE was used
      to quantify tricuspid annular displacement (TAD), from which RV longitudinal
      shortening fraction (LSF) was calculated. These STE derived indices were compared
      side-by-side with M-mode TAPSE measurements against cardiac magnetic resonance
      (CMR) derived RV ejection fraction (EF). METHODS: Echocardiography (Philips iE33,
      four-chamber view) and CMR (Siemens, 1.5 T) were performed on the same day in 63
      patients with a wide range of RV EF (23-70% by CMR). TAPSE was measured using M
      mode echocardiography. TAD and RV LSF were obtained using STE analysis (QLAB CMQ,
      Philips). TAPSE, TAD and RV LSF values were compared with RV EF obtained from CMR
      short axis stacks. RESULTS: STE analysis required <15 seconds and was able to
      track tricuspid annular motion in all patients as verified visually. Correlation
      between RV EF and TAD (0.61 free-wall, 0.65 septal) was similar to that with M
      mode TAPSE (0.63). However, STE-derived RV LSF showed a higher correlation with
      CMR EF (r = 0.78). CONCLUSION: RV LSF measurement by STE is fast and easy to
      obtain and provides more accurate evaluation of RV EF than the traditional M-mode
      TAPSE technique, when compared to CMR reference. (Echocardiography 2012;29:19
      24).

PMID- 21967481
TI  - 3D-QSAR and molecular docking studies on substituted isothiazole analogs as
      inhibitors against MEK-1 kinase.
AB  - MEK-1 and MEK-2 are dual-specificity kinases and important components in the
      mitogen-activated protein kinase pathway. These enzymes are crucial for normal
      cell survival and are also expressed in several types of cancers, making them
      important targets for drug design. We have applied an integrated in silico
      approach that combines comparative molecular field analysis, comparative
      molecular similarity indices analysis, and molecular docking to study the
      structural determinants for the recognition of substituted isothiazole analogs as
      allosteric inhibitors against MEK-1 kinase. The best 3D-QSAR models for
      comparative molecular field analysis and comparative molecular similarity indices
      analysis were selected based on statistical parameters. 3D contour maps suggested
      that bulky or long-chain substitutions at the X position on the core part
      decrease the inhibitory activity, and the presence of a hydrogen bond donor
      substitution enhances the activity. The bulky and electronegative substitutions
      at the Y position on the core part enhance the activity of the inhibitors.
      Molecular docking studies reveal a large and hydrophobic pocket that accommodates
      the Y substitution and a polar pocket that accommodates substitutions on the X
      position and forms hydrogen bonding interactions with MEK-1 kinase. The results
      of the 3D-QSAR analysis corroborate with the molecular docking results, and our
      findings will serve as a basis for further development of better allosteric
      inhibitors of MEK-1 kinase against several cancers.

PMID- 21967482
TI  - Solution structure of a 2:1 quindoline-c-MYC G-quadruplex: insights into G
      quadruplex-interactive small molecule drug design.
AB  - Unimolecular parallel-stranded G-quadruplex structures are found to be prevalent
      in gene promoters. The nuclease hypersensitivity element III(1) (NHE III(1)) of
      the c-MYC promoter can form transcriptionally active and silenced forms, and the
      formation of DNA G-quadruplex structures has been shown to be critical for c-MYC
      transcriptional silencing. The solution structure of a 2:1 quindoline-G
      quadruplex complex has been solved and shows unexpected features, including the
      drug-induced reorientation of the flanking sequences to form a new binding
      pocket. While both 3' and 5' complexes show overall similar features, there are
      identifiable differences that emphasize the importance of both stacking and
      electronic interactions. For the first time, we describe the importance of the
      shape of the ligand as well as the two flanking bases in determining drug binding
      specificity. These structures provide important insights for the structure-based
      rational design of drugs that bind to unimolecular parallel G-quadruplexes
      commonly found in promoter elements.

PMID- 21967484
TI  - Apicoectomies with the erbium laser: a complementary technique for retrograde
      endodontic treatment.
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficacy of erbium
      lasers for retrograde endodontic treatment, in terms of clinical outcome and
      therapeutic success. BACKGROUND DATA: Apicoectomy with retrograde filling is a
      well-established surgical procedure to treat teeth affected by persistent
      periapical lesions. The apical root end is generally removed with burs, and the
      adjacent periapical tissue curetted, or alternatively treated with ultrasound or
      laser. METHODS: Between 2000 and 2010, 65 apicoectomies were performed on
      necrotic teeth that presented apical lesions (29 men, 36 women). The lasers used
      in the study were the erbium:yttrium-aluminum-garnet (Er:YAG) laser, wavelength
      2940 nm, and the erbium,chromium-doped:yttrium-scandium-gallium-garnet
      (Er,Cr:YSGG) laser, wavelength 2780 nm. RESULTS: Of the 65 teeth in the study,
      failure only occurred in 9 CASES, MANIFESTING AFTER DIFFERENT TIMES. THE
      REMAINING PATIENTS, 86.15%, experienced no complications, and their treatment
      followed a positive course. CONCLUSIONS: Laser-assisted surgery increases the
      range of therapeutic approaches in the sphere of retrograde endodontic treatment.
      The results of this study show that the erbium laser, used for apicoectomy,
      results in a high success rate with considerable benefit in terms of clinical
      outcome and therapeutic success.

PMID- 21967483
TI  - Glu106 in the Orai1 pore contributes to fast Ca2+-dependent inactivation and pH
      dependence of Ca2+ release-activated Ca2+ (CRAC) current.
AB  - FCDI (fast Ca2+-dependent inactivation) is a mechanism that limits Ca2+ entry
      through Ca2+ channels, including CRAC (Ca2+ release-activated Ca2+) channels.
      This phenomenon occurs when the Ca2+ concentration rises beyond a certain level
      in the vicinity of the intracellular mouth of the channel pore. In CRAC channels,
      several regions of the pore-forming protein Orai1, and STIM1 (stromal interaction
      molecule 1), the sarcoplasmic/endoplasmic reticulum Ca2+ sensor that communicates
      the Ca2+ load of the intracellular stores to Orai1, have been shown to regulate
      fast Ca2+-dependent inactivation. Although significant advances in unravelling
      the mechanisms of CRAC channel gating have occurred, the mechanisms regulating
      fast Ca2+-dependent inactivation in this channel are not well understood. We have
      identified that a pore mutation, E106D Orai1, changes the kinetics and voltage
      dependence of the ICRAC (CRAC current), and the selectivity of the Ca2+-binding
      site that regulates fast Ca2+-dependent inactivation, whereas the V102I and E190Q
      mutants when expressed at appropriate ratios with STIM1 have fast Ca2+-dependent
      inactivation similar to that of WT (wild-type) Orai1. Unexpectedly, the E106D
      mutation also changes the pH dependence of ICRAC. Unlike WT ICRAC, E106D-mediated
      current is not inhibited at low pH, but instead the block of Na+ permeation
      through the E106D Orai1 pore by Ca2+ is diminished. These results suggest that
      Glu106 inside the CRAC channel pore is involved in co-ordinating the Ca2+-binding
      site that mediates fast Ca2+-dependent inactivation.

PMID- 21967485
TI  - The plasma membrane is involved in the visible light-tissue interaction.
AB  - OBJECTIVE: The aim of the present study was to determine whether the plasma
      membrane is also involved in the light-tissue interaction because of the
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidase electron chain, which
      can serve as a photosensitizer. BACKGROUND DATA: It has been suggested that the
      mechanism of photobiostimulation involves light-induced low levels of reactive
      oxygen species (ROS) that serve as signal transduction messengers. Production of
      ROS following visible-light irradiation was verified by the electron paramagnetic
      resonance (EPR) spin-trapping technique, and the mitochondrial cytochromes were
      suggested as the main cellular target for visible-light absorption. METHODS:
      Isolated sperm membranes were illuminated with visible light and the increase in
      oxygen radical production was measured using the EPR spin-trapping technique
      coupled with the probe 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). A broadband
      visible light source (400-800 nm) at 40-130 mW/cm(2) with appropriate filters
      provided the illumination. In order to determine whether the light-induced ROS
      production is a result of a photo-accelerated electron transfer in the enzyme
      catalyzed reaction with oxygen in the plasma membrane, or resulted from a
      photochemical reaction of the chromophores alone with oxygen, denatured membranes
      were irradiated as well. RESULTS: Visible-light-induced oxyradicals were detected
      in isolated sperm membranes. Blue light was found to be more effective than red.
      Illuminated denatured membranes produced the same amount of ROS as non-denatured
      membranes. CONCLUSIONS: Visible-light illumination, especially in the blue
      region, increases ROS levels in isolated plasma membranes. The mechanism of ROS
      formation is probably a photochemical reaction of the membranal chromophhores,
      for example, cytochromes or flavins with oxygen, and not an enzyme-catalyzed
      photochemical reaction.

PMID- 21967487
TI  - Programs for calibration-based Monte Carlo simulation of recharge areas.
AB  - One use of groundwater flow models is to simulate contributing recharge areas to
      wells or springs. Particle tracking can be used to simulate these recharge areas,
      but in many cases the modeler is not sure how accurate these recharge areas are
      because parameters such as hydraulic conductivity and recharge have errors
      associated with them. The scripts described in this article (GEN_LHS and
      MCDRIVER_LHS) use the Python scripting language to run a Monte Carlo simulation
      with Latin hypercube sampling where model parameters such as hydraulic
      conductivity and recharge are randomly varied for a large number of model
      simulations, and the probability of a particle being in the contributing area of
      a well is calculated based on the results of multiple simulations. Monte Carlo
      simulation provides one useful measure of the variability in modeled particles.
      The Monte Carlo method described here is unique in that it uses parameter sets
      derived from the optimal parameters, their standard deviations, and their
      correlation matrix, all of which are calculated during nonlinear regression model
      calibration. In addition, this method uses a set of acceptance criteria to
      eliminate unrealistic parameter sets.

PMID- 21967489
TI  - An unusual presentation of idiopathic basal cell carcinoma in an 8-year-old
      child.
AB  - We report the unusual case of a young child who developed an idiopathic basal
      cell carcinoma (BCC). The patient was otherwise healthy, with no history of
      excessive sun or radiation exposure or any predisposing factors for nonmelanoma
      skin cancer. This is a rare case that exemplifies the need for pediatricians and
      dermatologists to be aware that BCC may occur in children, even if they have no
      predisposing factors.

PMID- 21967486
TI  - Influence of injectable hyaluronic acid hydrogel degradation behavior on
      infarction-induced ventricular remodeling.
AB  - Increased myocardial wall stress after myocardial infarction (MI) initiates the
      process of adverse left ventricular (LV) remodeling that is manifest as
      progressive LV dilatation, loss of global contractile function, and symptomatic
      heart failure, and recent work has shown that reduction in wall stress through
      injectable bulking agents attenuates these outcomes. In this study, hyaluronic
      acid (HA) was functionalized to exhibit controlled and tunable mechanics and
      degradation once cross-linked, in an attempt to assess the temporal dependency of
      mechanical stabilization in LV remodeling. Specifically, two hydrolytically
      degrading (low and high HeMA-HA, degrading in ~3 and 10 weeks, respectively) and
      two stable (low and high MeHA, little mass loss even after 8 weeks) hydrogels
      with similar initial mechanics (low: ~7 kPa; high: ~35-40 kPa) were evaluated in
      an ovine model of MI. Generally, the more stable hydrogels maintained myocardial
      wall thickness in the apical and basilar regions more efficiently (low MeHA:
      apical: 6.5 mm, basilar: 7 mm, high MeHA: apical: 7.0 mm basilar: 7.2 mm) than
      the hydrolytically degrading hydrogels (low HeMA-HA: apical: 3.5 mm, basilar: 6.0
      mm, high HeMA-HA: apical: 4.1 mm, basilar: 6.1 mm); however, all hydrogel groups
      were improved compared to infarct controls (IC) (apical: 2.2 mm, basilar: 4.6
      mm). Histological analysis at 8 weeks demonstrated that although both degradable
      hydrogels resulted in increased inflammation, all treatments resulted in
      increased vessel formation compared to IC. Further evaluation revealed that while
      high HeMA-HA and high MeHA maintained reduced LV volumes at 2 weeks, high MeHA
      was more effective at 8 weeks, implying that longer wall stabilization is needed
      for volume maintenance. All hydrogel groups resulted in better cardiac output
      (CO) values than IC.

PMID- 21967490
TI  - A randomized, placebo- and active-controlled, parallel-group, multicentre,
      investigator-blinded study of four treatment regimens of posaconazole in adults
      with toenail onychomycosis.
AB  - BACKGROUND: Onychomycosis accounts for up to 50% of all onychopathies.
      OBJECTIVES: To evaluate the efficacy of four posaconazole regimens compared with
      placebo in the treatment of toenail onychomycosis, to assess the safety and
      tolerability of posaconazole, and to estimate the relative efficacy of
      posaconazole against terbinafine. METHODS: A phase 2B, randomized, placebo- and
      active-controlled, parallel-group, multicentre, investigator-blinded (double
      blind for placebo) study (ClinicalTrials.gov identifier: NCT00491764).
      Onychomycosis patients aged 18-75years (n=218) were randomized equally to one of
      six treatment regimens: posaconazole (oral suspension) 100, 200 or 400mg once
      daily (24weeks); posaconazole 400 mg once daily (12weeks); terbinafine (tablets)
      250mg once daily (12weeks); or placebo (24weeks). The primary efficacy variable
      was complete cure (negative mycology and 0% nail involvement) at week 48.
      RESULTS: All posaconazole treatment arms had a significantly (P<=0.012) greater
      proportion of patients with complete cure at week 48 compared with placebo. The
      proportions of patients with complete cure were numerically higher for
      posaconazole 200mg/24weeks (54.1%) and 400mg/24weeks (45.5%), but lower for
      400mg/12weeks (20%) compared with terbinafine (37%; differences were not
      statistically significant). Posaconazole was well tolerated. Seven patients
      receiving posaconazole withdrew because of asymptomatic liver enzyme increases,
      as mandated by protocol discontinuation criteria. CONCLUSIONS: The efficacy and
      favourable safety profile of posaconazole suggest a potential new treatment for
      onychomycosis. The availability of low-cost generic terbinafine may limit
      posaconazole use to second-line treatment of infections refractory to, or
      patients intolerant of, terbinafine, or nondermatophyte mould infections.

PMID- 21967491
TI  - Going to scale: a nonrandomized nationwide trial of the KiVa antibullying program
      for grades 1-9.
AB  - OBJECTIVE: The effects of school-based antibullying programs have typically been
      examined on small samples, with number of schools ranging from 1 to 78
      (Farrington & Ttofi, 2009). This study investigated the effectiveness of the KiVa
      antibullying program in the beginning of its nationwide implementation in
      Finland. METHOD: At each time point, the participants included 888 schools with
      approximately 150,000 students in 11,200 classrooms in Grades 1-9 (8-16 years of
      age; 51% boys and 49% girls). Victims and bullies were identified with the global
      questions from the Revised Olweus Bully/Victim Questionnaire (Olweus, 1996),
      utilizing the criteria suggested by Solberg and Olweus (2003). The program
      effects were examined by calculating odds ratios based on a cohort-longitudinal
      design, correcting the standard errors for clustering. RESULTS: During the first
      9 months of implementation, the KiVa program reduced both victimization and
      bullying, with a control/intervention group odds ratio of 1.22 (95% CI [1.19,
      1.24]) for victimization and 1.18 (95% CI [1.15, 1.21]) for bullying.
      CONCLUSIONS: Generalized to the Finnish population of 500,000 students, this
      would mean a reduction of approximately 7,500 bullies and 12,500 victims.

PMID- 21967492
TI  - Brief strategic family therapy versus treatment as usual: results of a multisite
      randomized trial for substance using adolescents.
AB  - OBJECTIVE: To determine the effectiveness of brief strategic family therapy
      (BSFT; an evidence-based family therapy) compared to treatment as usual (TAU) as
      provided in community-based adolescent outpatient drug abuse programs. METHOD: A
      randomized effectiveness trial in the National Drug Abuse Treatment Clinical
      Trials Network compared BSFT to TAU with a multiethnic sample of adolescents (213
      Hispanic, 148 White, and 110 Black) referred for drug abuse treatment at 8
      community treatment agencies nationwide. Randomization encompassed both
      adolescents' families (n = 480) and the agency therapists (n = 49) who provided
      either TAU or BSFT services. The primary outcome was adolescent drug use,
      assessed monthly via adolescent self-report and urinalysis for up to 1 year post
      randomization. Secondary outcomes included treatment engagement (>=2 sessions),
      retention (>=8 sessions), and participants' reports of family functioning 4, 8,
      and 12 months following randomization. RESULTS: No overall differences between
      conditions were observed in the trajectories of self-reports of adolescent drug
      use. However, the median number of days of self-reported drug use was
      significantly higher, chi2(1) = 5.40, p < .02, in TAU (Mdn = 3.5, interquartile
      range [IQR] = 11) than BSFT (Mdn = 2, IQR = 9) at the final observation point.
      BSFT was significantly more effective than TAU in engaging, chi2(1) = 11.33, p <
      .001, and retaining, chi2(1) = 5.66, p < .02, family members in treatment and in
      improving parent reports of family functioning, chi2(2) = 9.10, p < .011.
      CONCLUSIONS: We discuss challenges in treatment implementation in community
      settings and provide recommendations for further research.

PMID- 21967493
TI  - Comprehensive study of tartrazine/cationic surfactant interaction.
AB  - Interaction of a food dye, tartrazine, with some cationic conventional and gemini
      surfactants, tetradecyltrimethylammonium bromide (TTAB), N,N'-ditetradecyl
      N,N,N',N'-tetramethyl-N,N'-butanediyl-diammonium dibromide (14,4,14), and N,N'
      didodecyl-N,N,N',N'-tetramethyl-N,N'-butanediyl-diammonium dibromide (12,4,12),
      were first investigated comprehensively employing conductometry, tensiometry, and
      UV-visible spectroscopy. Tartrazine was found to behave in the same manner as
      aromatic counterions. The formation of ion pairs reflected as a considerable
      increase of the surfactant efficiency in tensiometry plots and their
      stoichiometry were determined by Job's method of continuous variations. For the
      tartrazine/TTAB system, nonionic DS(3), ionic DS(2-), and/or DS(2)(-) ion pairs,
      their small premicelles, and tartrazine-rich micelles were constituted as well as
      dye-containing TTAB-rich micelles. Insoluble J-aggregates of DS(-) ion pairs and
      cylindrical surfactant-rich micelles were also formed in tartrazine/gemini
      surfactant systems and recognized by transmission electron microscopy. The zeta
      potential and the size of the aggregates were determined using dynamic light
      scattering and confirmed the suggested models for the processes happening in each
      system. Cyclic voltammetry was applied successfully to track all of these species
      using tartrazine's own reduction peak current for the first time.

PMID- 21967494
TI  - Kaposi's sarcoma in HIV-infected women and men in Nigeria.
AB  - Abstract Kaposi's sarcoma (KS) in women with HIV infection is observed to have
      increased from recent studies. To understand the gender-related differences of
      AIDS-KS in Nigeria, we conducted a prospective study of the clinical, virologic,
      and immunologic features of newly diagnosed AIDS-KS patients. Prevalence was
      similar in both genders. There were differences in the distribution of the
      lesions and the CD4 count in women was significantly lower.

PMID- 21967495
TI  - Measuring stigma among health care and social service providers: The HIV/AIDS
      Provider Stigma Inventory.
AB  - Initial validation of the HIV/AIDS Provider Stigma Inventory (HAPSI), piloted on
      a sample of 174 nursing students, supported the psychometric qualities of a suite
      of measures capturing tendencies to stigmatize and discriminate against people
      living with HIV/AIDS (PLHA). Derived from social psychology and mindfulness
      theories, separate scales addressing awareness, acceptance, and action were
      designed to include notions of labeling, stereotyping, outgrouping, and
      discriminating. These were enhanced to capture differences associated with
      personal characteristics of PLHA that trigger secondary stigma (e.g., sexual
      orientation, injection drug use, multiple sex partners) and fears regarding
      instrumental and symbolic stigma. Reliabilities were strong (coefficients alpha
      for 16 of 19 resulting measures ranged from 0.80 to 0.98) and confirmatory factor
      analyses indicated good model fit for two multidimensional (Awareness and
      Acceptance) and one unidimensional (Action) measure. Evidence of convergent
      construct validity supported accuracy of primary constructs. Implications for
      training and professional socialization in health care are discussed.

PMID- 21967496
TI  - Assessing the application of acute toxic gas standards.
AB  - OBJECTIVE: In this paper, we compare acute toxic gas standards developed for
      occupational, military, and civilian use that predict or establish guidelines for
      limiting exposure to inhaled toxic gases. CONTEXT: Large disparities between
      guidelines exist for similar exposure scenarios, raising questions about why
      differences exist, as well as the applicability of each standard. The motivation
      and rationale behind the development of the standards is explored with emphasis
      on the experimental data used to set the standards. METHODS: The Toxic Gas
      Assessment Software (TGAS) is used to quantitatively compare current acute
      exposure standards, such as: Acute Exposure Guidelines (AEGL), Immediate Danger
      to Life or Health (IDLH), Purser, International Organization for Standardization
      (ISO 13571), and Federal Aviation Administration (FAA). The TGAS software does
      this by calculating the body-mass-normalized internal doses of each gas exposure
      in each standard, which is then plotted on a cumulative distribution function for
      a normal or susceptible population to visualize the relationship of the standards
      to each other. To focus the comparison, acute toxic gas standards for five common
      fire gases, carbon monoxide (CO), hydrogen cyanide (HCN), hydrogen chloride
      (HCl), nitrogen dioxide (NO2), and acrolein (C3H4O), are explored. RESULTS: It
      was found that differences between standards can be reconciled when the target
      population, effect endpoint, and incidence level are taken into account.
      CONCLUSION: By analyzing the standards with respect to these factors, we can
      acquire a better understanding of the applicability of each.

PMID- 21967498
TI  - Foam cell formation of alveolar macrophages in Clara cell ablated mice inhaling
      crystalline silica.
AB  - We investigated the function of Clara cells in vivo during exposure to inhaled
      crystalline silica by morphological and immunohistochemical examination of intra
      alveolar cells and alveolar macrophages in Clara cell-ablated mice. The Clara
      cells of male FVB/n mice (8-12 weeks old) were ablated by intraperitoneal
      administration of naphthalene (300 mg/kg). The mice were then exposed to
      crystalline silica (Min-U-Sil-5, 97.1 +/- 9.5 mg/m3, 6 hours/day, 5 days/week)
      for up to two weeks. The lungs were assessed by morphometry, as well as by
      immunohistochemistry of CD36, lectin-like oxygenated low-density lipoprotein
      receptor (LOX)-1, and matrix metalloproteinases (MMPs) -2, -9 and -12. There was
      a significantly greater number of intra-alveolar cells in Clara cell-ablated
      mouse groups than in wild-type mouse groups that were exposed to crystalline
      silica. A marked number of foamy alveolar macrophages were only detected in the
      Clara cell-ablated group exposed to crystalline silica, indicating that Clara
      cells inhibit infiltration and foam cell formation of alveolar macrophages.
      Immunohistochemical analysis indicated that foamy alveolar macrophages in the
      Clara cell-ablated group that inhaled crystalline silica overexpress CD36 and LOX
      1, indicating upregulation of scavenger receptors of alveolar macrophages. These
      cells also express MMP-2, -9 and -12, suggesting increased gelatinolytic and
      elastolytic activities. Our findings suggest that Clara cells not only inhibit
      infiltration of alveolar macrophages but also their phagocytotic and
      gelatinolytic functions in silica-induced pulmonary injury.

PMID- 21967497
TI  - Heterozygosity in the glutathione synthesis gene Gclm increases sensitivity to
      diesel exhaust particulate induced lung inflammation in mice.
AB  - CONTEXT: Inhalation of ambient fine particulate matter (PM2.5) is associated with
      adverse respiratory and cardiovascular effects. A major fraction of PM2.5 in
      urban settings is diesel exhaust particulate (DEP), and DEP-induced lung
      inflammation is likely a critical event mediating many of its adverse health
      effects. Oxidative stress has been proposed to be an important factor in PM2.5
      induced lung inflammation, and the balance between pro- and antioxidants is an
      important regulator of this inflammation. An important intracellular antioxidant
      is the tripeptide thiol glutathione (GSH). Glutamate cysteine ligase (GCL)
      carries out the first step in GSH synthesis. In humans, relatively common genetic
      polymorphisms in both the catalytic (Gclc) and modifier (Gclm) subunits of GCL
      have been associated with increased risk for lung and cardiovascular diseases.
      OBJECTIVE: This study was aimed to determine the effects of Gclm expression on
      lung inflammation following DEP exposure in mice. MATERIALS AND METHODS: We
      exposed Gclm wild type, heterozygous, and null mice to DEP via intranasal
      instillation and assessed lung inflammation as determined by neutrophils and
      inflammatory cytokines in lung lavage, inflammatory cytokine mRNA levels in lung
      tissue, as well as total lung GSH, Gclc, and Gclm protein levels. RESULTS: The
      Gclm heterozygosity was associated with a significant increase in DEP-induced
      lung inflammation when compared to that of wild type mice. DISCUSSION AND
      CONCLUSION: This finding indicates that GSH synthesis can mediate DEP-induced
      lung inflammation and suggests that polymorphisms in Gclm may be an important
      factor in determining adverse health outcomes in humans following inhalation of
      PM2.5.

PMID- 21967499
TI  - Effect of oxidation and extent of oxidation on biologically active PACs in
      asphalt products.
AB  - Recent studies have reported divergent results in rodent cancer assays using fume
      condensates from a variety of asphalt products. This paper presents results of a
      study investigating the role of oxidation, or extent of oxidation, on these
      findings. Five straight run asphalts, made from widely used crude oils, were used
      as inputs to both production scale and laboratory oxidation units and processed
      to a range of softening points used in common roofing products. For each of the
      five asphalts studied, the oxidation reaction significantly decreased measures of
      polycyclic aromatic compounds (PACs) that have been linked, previously and in
      analyses included in this study, to tumor induction in rodent bioassays.
      Mutagenicity index determined by the modified Ames assay was reduced between 41%
      and 50% from the input asphalt to the final oxidized product. A fluorescence
      method tuned to a subset of PAC compounds that have been associated with
      carcinogenic behavior in mouse bioassays was reduced between 39% and 71%. The
      decrease was largest in the first quarter of the oxidation reaction. These
      findings indicate that oxidation, by itself, was not a likely factor in the tumor
      induction seen in the previous studies. Rather, other factors such as the
      conditions of fume generation and crude source (coupled with possible differences
      in distillation endpoints) were more likely to have determined the outcomes.
      Analyses of previously published data, presented in this paper, suggest that the
      modified Ames and fluorescence assays are valuable screening tools for use in
      future health-related asphalt research.

PMID- 21967500
TI  - The Victory stitch: a novel running v-shaped horizontal mattress suturing
      technique.

PMID- 21967501
TI  - The effects of expansions, questions and cloze procedures on children's
      conversational skills.
AB  - The effectiveness of expansion as a technique for facilitating children's
      language and conversational skills is well known (Scherer and Olswang, 1984).
      Expansion, however, can appear alone or in combination with other techniques.
      Using a repeated measures design, this study aimed to compare the effects of
      expansion alone (EA); expansion combined with wh-questions (EQ); and expansion
      followed by a cloze procedure (EC) on the conversational skills of eight
      preschool children with conversational difficulties. Results showed that while
      there were no significant differences in child verbal topic maintaining responses
      across all techniques, EA elicited a significantly higher number of topic
      extensions, more non-verbal topic maintaining responses and fewer 'non-relevant
      responses' from the children, than either EQ or EC. The positive effects of each
      technique on the pragmatic appropriateness in conversations suggest that they
      could be used strategically in language intervention to ensure greater
      therapeutic effect.

PMID- 21967502
TI  - Hypertension after heart and heart/lung transplantation in childhood--study on
      the evolution of short-term blood pressure regulation.
AB  - Arterial hypertension complicates the follow-up of heart- and heart/lung
      transplanted children. We investigated the evolution of BRS as short-time BP
      regulation mechanism and BP after heart and heart/lung transplantation. Twenty
      patients (15 males; mean age 15.1 +/- 4.3 yr) were studied twice at intervals of
      2.96 +/- 0.87 yr. BRS was calculated using non-invasive beat-to-beat BP
      measurement system. HRV was calculated (LF, sympathetic influence; HF,
      parasympathetic influence). BRS increased in 10 patients (3.67 +/- 1.43 ms/mmHg
      vs. 7.59 +/- 3.40 mmHg, p = 0.005) (group 1). Six of 10 patients received
      antihypertensive medication. BRS decreased or remained unchanged in 10 patients
      (8.93 +/- 7.9 ms/mmHg vs. 5.32 +/- 6.6 ms/mmHg, p = 0.008) (group 2) with 9/10
      patients necessitating antihypertensive medication. Group 1 showed LF/HF increase
      (LF/HF 1.03 +/- 0.9 vs. 4.36 +/- 2.32, p = 0.03); group 2 showed LF/HF decrease
      (LF/HF 3.7 +/- 2.1 vs. 1.84 +/- 1.1, p = 0.023). Evolution of BRS after heart and
      heart/lung transplantation in childhood seems to influence the necessity of
      antihypertensive medication. With time, increasing short-time BP regulation
      involving sympathetic reinnervation may improve BP.

PMID- 21967504
TI  - Fluorescence anisotropy based single liposome assay to measure molecule-membrane
      interactions.
AB  - Nanometer-scaled liposomes are used frequently for research, therapeutic, and
      analytical applications as carriers for water-soluble molecules. Recent technical
      advances allow the monitoring of single liposomes, which provides information on
      heterogeneous properties that were otherwise hidden due to ensemble averaging.
      Recent observations demonstrated that the efficiency of entrapping water-soluble
      molecules increases with decreasing vesicle size. The molecular mechanism behind
      this observation is not clear, but enhanced molecule-membrane interactions due to
      the increase of the surface area-to-volume ratio could play an important role. To
      investigate this hypothesis, we extended our single liposome assay based on
      confocal fluorescence imaging by implementation of fluorescence anisotropy. This
      combination has not been widely exploited, and confocal fluorescence anisotropy
      imaging in particular has seldom been used. We investigated different small dye
      molecules and were able to determine if these molecules interact or not with the
      liposome membrane. We confirm the liposome size-dependent entrapment of molecules
      whereas the molecule-membrane interactions appear to be independent of liposome
      size. Our fluorescence anisotropy assay can be used as a general method to
      investigate molecule-membrane interactions or molecule-molecule interactions in a
      high-throughput manner in nanometer-scaled containers like liposomes.

PMID- 21967503
TI  - The molecular epidemiology of circulating rotaviruses: three-year surveillance in
      the region of Monastir, Tunisia.
AB  - BACKGROUND: Rotavirus infection is the most common cause of severe, dehydrating,
      gastroenteritis among children worldwide. In developing countries, approximately
      1440 children die from rotavirus infections each day, with an estimated 527,000
      annually. In infants, rotavirus is estimated to cause more than 2 million
      hospitalizations every year depending on the income level of the country. The
      purpose of this study was to estimate the proportion of rotavirus gastroenteritis
      and identify the distribution of circulating G and P genotype rotavirus strains
      among children consulting several dispensaries in the region of Monastir
      (outpatients departments) or admitted to Monastir University Hospital (inpatients
      department) with acute gastroenteritis. METHODS: This study was undertaken during
      a 3-year period from April 2007 to April 2010 in Tunisian children under 13
      suffering from acute gastroenteritis. Group A rotaviruses were detected in stools
      by ELISA and genotyped using multiplex reverse transcription PCRs with type
      specific primers on the basis of their outer capsid proteins. Statistical
      analyses were performed with SPSS software, version 19. RESULTS: Of the 435 stool
      samples from children with acute gastroenteritis, 27.6% were positive for
      rotavirus A. The predominant G type was G1 (37.5%), followed by G3 (25%), G2
      (17.5%), G4 (12.5%), G9 (2.5%) and three mixed-G infections G3G4 (2.5%) were
      identified. Only P[8] (80.8%), P[4] (16.7%) and P[9] (0.8%) genotypes were found.
      The predominant single G/P combination was G1P[8] (37.5%), followed by G3P[8]
      (25%), G2P[4] (16.7%), G4P[8] (12.5%), G9P[8] (1.7%) and one case of the unusual
      combination G9P[9] (0.8%). The G-mixed types G3G4 combined with P[8] (2.5%).
      Infants less than 3 months of age were most frequently affected. The prevalence
      of rotavirus infection peaked in the winter season, when temperatures were low,
      and decreased in summer. CONCLUSIONS: Rotavirus gastroenteritis is a common
      disease associated with significant morbidity, mortality, and economic burden.
      Epidemiological knowledge of rotavirus is critical for the development of
      effective preventive measures, including vaccines. These data will help to make
      informed decisions as to whether rotavirus vaccine should be considered for
      inclusion in Tunisia's National Immunisation Programme.

PMID- 21967505
TI  - Epigenetic dysregulation of GATA1 is involved in myelodysplastic syndromes
      dyserythropoiesis.
AB  - Myelodysplastic syndromes (MDS) are characterized by dyserythropoiesis resulting
      in anemia. This pathological hallmark is incompletely understood. Notch signaling
      has been linked to impaired erythropoietic and megakaryopoietic development of
      CD34+ progenitor cells, but its role in MDS is unclear. We have analyzed the
      transcriptional activity of Notch pathway elements and its association with the
      key erythroid factor globin transcription factor 1 (GATA1) and the apoptosis
      regulatory gene B-cell lymphoma-xl (BCLxl) in MDS. The methylation of GATA1
      erythroid promoter CpG dinucleotides flanking cis-regulatory elements, including
      an N-box suppressor binding site for HES1 and a GATA-box binding site, was
      examined in normal and MDS erythropoiesis. We have generated a kinetic in vitro
      model of MDS erythropoiesis using CD34+ bone marrow cells from healthy donors (n
      = 7) and patients with MDS (low risk: RA/n = 6, RARS/n = 3; high risk: RAEB/n =
      4, RAEB-T/n = 2). RNA expression of GATA1, BCLxl, DLK1, Notch1, HES1, and HERP2
      was measured by real-time RT-PCR (qPCR). DNA methylation at seven CpG
      dinucleotides of the GATA1 gene promoter was quantitatively analyzed by
      pyrosequencing of bisulfite-treated genomic DNA at any specific time point. For
      the Notch pathway elements, no conclusive expression differences were found
      between MDS and normal erythropoiesis. But we found steadily up-regulated RNA
      expression of GATA1 and of BCLxl during late normal erythropoietic
      differentiation. In contrast, during MDS, erythropoiesis a loss of typical up
      regulation of GATA1 and BCLxl was observed. Hypermethylation of CpG dinucleotides
      flanking the repressor HES1 binding site within the 5' region of GATA1 was
      detected particularly during late MDS erythropoiesis. Interestingly, decremental
      GATA1 promotor methylation values were seen during normal erythropoiesis matching
      GATA1 RNA up-regulation. Our data show that the critical erythropoietic
      transcription factor GATA1 as well as the antiapoptotic molecule BCLxl fails to
      be normally up-regulated during MDS erythropoiesis. The higher residual 5'-GATA1
      methylation values in MDS erythropoiesis but decremental loss thereof in normal
      erythropoiesis suggest a gene dose effect for GATA1 during erythropoiesis being
      finely tuned by CpG methylation. Its dysregulation may contribute to the
      ineffective erythropoiesis observed in MDS.

PMID- 21967506
TI  - The use of nonsteroidal anti-inflammatory drugs and the risk of Barrett's
      oesophagus.
AB  - BACKGROUND: Epidemiological studies have consistently reported inverse
      associations between nonsteroidal anti-inflammatory drugs (NSAIDs) and
      oesophageal adenocarcinoma, but few have investigated associations with the
      precursor lesion, Barrett's oesophagus. AIM: To investigate the relationship
      between NSAID use and risk of Barrett's oesophagus. METHODS: We conducted a large
      population-based case-control study that collected information on patterns of
      intake for aspirin and non-aspirin NSAIDs during the past 5 years and other
      exposures from 285 patients with nondysplastic Barrett's oesophagus, 108 patients
      with dysplastic Barrett's oesophagus, and two separate control groups: 313
      endoscopy patients with acute inflammatory changes ('inflammation controls') and
      644 population controls. We calculated odds ratios (ORs) and 95% CIs using
      unconditional logistic regression. RESULTS: Use of aspirin was not associated
      with nondysplastic Barrett's oesophagus when compared with population (OR=1.01,
      95% CI 0.71-1.43) or inflammation controls (OR=1.16, 95% CI 0.80-1.68). Whereas
      we observed significant risk reductions for use of non-aspirin NSAIDs when
      nondysplastic Barrett's oesophagus cases were compared with population controls
      (OR=0.69, 95% CI 0.49-0.97), the effect was weaker and nonsignificant when cases
      were compared with inflammation controls (OR=0.82, 95% CI 0.57-1.18), and no dose
      response effects were present in either analysis. We found no evidence that
      aspirin or non-aspirin NSAID use conferred risk reductions for dysplastic
      Barrett's oesophagus, regardless of the control series. We excluded effect
      modification by known risk factors as an explanation for these null findings.
      CONCLUSIONS: We found little support for an inverse association between use of
      NSAIDs and Barrett's oesophagus. The question of whether or not these medications
      prevent the onset of Barrett's oesophagus remains open.

PMID- 21967507
TI  - Variables involved in the cue modulation of the startle reflex in alcohol
      dependent patients.
AB  - Cue modulation of the startle reflex is a paradigm that has been used to
      understand the emotional mechanisms involved in alcohol dependence. Attenuation
      of the startle reflex has been demonstrated when alcohol-dependent subjects are
      exposed to alcohol-related stimuli. However, the role of clinical variables on
      the magnitude of this response is unknown. The objective of this study was to
      determine the relationship between a number of clinical variables-severity of
      alcoholism, family history of alcoholism (FHA+), personality traits related to
      the sensitivity to reward-and the startle reflex response when subjects with
      alcohol dependence were viewing alcohol-related cues. After detoxification, 98
      participants completed self-report instruments and had eye blink electromyograms
      measured to acoustic startle probes [100-millisecond burst of white noise at 95
      dB(A)] while viewing alcohol-related pictures, and standardised appetitive,
      aversive and neutral control scenes. Ninety-eight healthy controls were also
      assessed with the same instruments. There were significant differences on alcohol
      startle magnitude between patients and controls. Comparisons by gender showed
      that women perceived alcohol cues and appetitive cues more appetitive than men.
      Male and female patients showed more appetitive responses to alcohol cues when
      compared with their respective controls. Our patients showed an appetitive effect
      of alcohol cues that was positively related to severity of alcohol dependence,
      sensitivity to reward and a FHA+. The data confirmed that the pattern of the
      modulation of the acoustic startle reflex reveals appetitive effects of the
      alcohol cues and extended it to a variety of clinical variables.

PMID- 21967508
TI  - Homogenous bonding--case report and 18-year follow up.
AB  - Fracture of the anterior teeth by trauma is the most frequent type of injury
      affecting the permanent dentition, especially the maxillary central incisors.
      When the fragment is not available or its use is not recommended, donated
      extracted teeth (homogenous bonding) can be used. The aim of this paper is to
      report the successful 18-year follow up of a maxillary central incisor fracture
      in which homogenous bonding was performed.

PMID- 21967509
TI  - M-plane core-shell InGaN/GaN multiple-quantum-wells on GaN wires for
      electroluminescent devices.
AB  - Nonpolar InGaN/GaN multiple quantum wells (MQWs) grown on the {11-00} sidewalls
      of c-axis GaN wires have been grown by organometallic vapor phase epitaxy on c
      sapphire substrates. The structural properties of single wires are studied in
      detail by scanning transmission electron microscopy and in a more original way by
      secondary ion mass spectroscopy to quantify defects, thickness (1-8 nm) and In
      composition in the wells (~16%). The core-shell MQW light emission
      characteristics (390-420 nm at 5 K) were investigated by cathodo- and
      photoluminescence demonstrating the absence of the quantum Stark effect as
      expected due to the nonpolar orientation. Finally, these radial nonpolar quantum
      wells were used in room-temperature single-wire electroluminescent devices
      emitting at 392 nm by exploiting sidewall emission.

PMID- 21967511
TI  - Electrophoresis of a charged colloidal particle in porous media: boundary effect
      of a solid plane.
AB  - Electrokinetic treatments such as the electrophoretic technique have been applied
      successfully to various soil remediation and contaminant removal situations. To
      understand further the fundamental features involved, the electrophoretic motion
      of a charged particle in porous media is investigated theoretically in this
      study, focusing on the boundary effect of a nearby solid plane toward which the
      particle moves perpendicularly. The porous medium is modeled as a Brinkman fluid
      with a characteristic screening length (lambda(-1)) that can be obtained directly
      from the experimental data. General electrokinetic equations are used to describe
      the system and are solved with a pseudospectral method based on Chebyshev
      polynomials. We found that the particle motion is deterred by the boundary effect
      in general. The closer the particle is to the boundary, the more severe this
      effect is. Up to a 90% reduction in particle mobility is observed in some
      situations. This indicates that a drastic overestimation (10-fold!) of the
      overall transport rate of particles may occur for large-scale in situ operations
      in porous media, such as soil remediation utilizing large planar electrodes,
      should a portable analytical formula valid for bulk systems only be used.
      Correction factors for various situations in porous media are presented as
      convenient charts with which to aid engineers and researchers in the field of
      environmental engineering, for instance, as a realistic estimation of the actual
      transport rate obtainable. In addition, the results of present study can be
      applied to biomedical engineering and drug delivery as well because polymer gels
      and skin barriers both have a porous essence.

PMID- 21967510
TI  - Oxidative modification of native protein residues using cerium(IV) ammonium
      nitrate.
AB  - A new protein modification strategy has been developed that is based on an
      oxidative coupling reaction that targets electron-rich amino acids. This strategy
      relies on cerium(IV) ammonium nitrate (CAN) as an oxidation reagent and results
      in the coupling of tyrosine and tryptophan residues to phenylene diamine and
      anisidine derivatives. The methodology was first identified and characterized on
      peptides and small molecules, and was subsequently adapted for protein
      modification by determining appropriate buffer conditions. Using the optimized
      procedure, native and introduced solvent-accessible residues on proteins were
      selectively modified with polyethylene glycol (PEG) and small peptides. This
      unprecedented bioconjugation strategy targets these under-utilized amino acids
      with excellent chemoselectivity and affords good-to-high yields using low
      concentrations of the oxidant and coupling partners, short reaction times, and
      mild conditions.

PMID- 21967512
TI  - High prevalence of subclinical rheumatic heart disease in pregnant women in a
      developing country: an echocardiographic study.
AB  - OBJECTIVES: Pregnant women with rheumatic heart disease (RHD) carry a high risk
      of morbidity and mortality. In this study the prevalence of subclinical RHD in
      pregnant women in Keren, Eritrea was assessed using echocardiography. METHODS AND
      RESULTS: A prospective cross sectional survey of pregnant women attending a
      midwife consultation was carried out by two specially trained medical students
      and an experienced cardiologist. The women were screened by the medical students
      using echocardiography. All recordings were reviewed and evaluated by the
      experienced cardiologist before a final diagnosis was given. Eight of the 348
      screened women had definite RHD. This corresponds to a prevalence of 2.3%, 95% CI
      (0.7-3.9). CONCLUSION: 2.3% of the pregnant women in Keren were found to have
      subclinical RHD.

PMID- 21967513
TI  - Neurorehabilitation in Sri Lanka: an emerging sub-specialty for neurology
      trainees.
AB  - Sri Lanka has an ageing population with an impending epidemic of stroke at hand.
      Stroke is the leading cause of adult disability in Sri Lanka. Sri Lanka has seen
      many recent advances in stroke services in the recent past providing a benchmark
      example for the countries in the Asia Pacific region, modeling the best care for
      stroke patients across the region with limited facilities they have. Three
      postgraduate trainees in neurology and medicine from Sri Lanka will spend a year
      at Western Health/ University of Melbourne, Melbourne, Australia for a period of
      12 months for training in neurorehabilitation for stroke. It is timely for
      neurology trainees and trainees in internal medicine in Sri Lanka to be
      interested in neurorehabilitation. We sincerely hope the Board of study of
      Neurology, Post Graduate Institute of Medicine, Colombo, Sri Lanka will take the
      necessary steps to establish neurorehabilitation as an emerging sub-specialty for
      neurology trainees in Sri Lanka now.

PMID- 21967514
TI  - Lewis acid catalyzed cyclization of glycals/2-deoxy-D-ribose with arylamines:
      additional findings on product structure and reaction diastereoselectivity.
AB  - The cyclization reactions of arylamines with 2-deoxy-D-ribose or glycals were
      reinvestigated in the current report. In the montmorillonite KSF- or InCl(3)
      initiated reactions of 2-deoxy-D-ribose with arylamines, a pair of diastereomeric
      tetrahydro-2H-pyran-fused tetrahydroquinolines was obtained in a nearly 1:1 ratio
      where the structure of one diastereomer was incorrectly assigned in the
      literature. Meanwhile, the diastereoselectivity in InBr(3)-catalyzed cyclization
      of glycals with arylamines was also incorrectly reported previously. It was found
      that high diastereomeric selectivity was achieved only when a C5-substituted
      glycal was used; otherwise, a pair of diastereomers was obtained in moderate
      yield with 1:1 diastereomeric ratio. Furthermore, tetrahydrofuran-fused
      tetrahydroquinolines 5b and 5b' were also prepared successfully by using TBDPS
      protected ribose as the glycal precursor and montmorillonite KSF as the
      activator.

PMID- 21967515
TI  - Regulation by mitochondrial superoxide and NADPH oxidase of cellular formation of
      nitrated cyclic GMP: potential implications for ROS signalling.
AB  - 8-Nitro-cGMP (8-nitroguanosine 3',5'-cyclic monophosphate) is a nitrated
      derivative of cGMP, which can function as a unique electrophilic second messenger
      involved in regulation of an antioxidant adaptive response in cells. In the
      present study, we investigated chemical and biochemical regulatory mechanisms
      involved in 8-nitro-cGMP formation, with particular focus on the roles of ROS
      (reactive oxygen species). Chemical analyses demonstrated that peroxynitrite
      dependent oxidation and myeloperoxidase-dependent oxidation of nitrite in the
      presence of H2O2 were two major pathways for guanine nucleotide nitration. Among
      the guanine nucleotides examined, GTP was the most sensitive to peroxynitrite
      mediated nitration. Immunocytochemical and tandem mass spectrometric analyses
      revealed that formation of 8-nitro-cGMP in rat C6 glioma cells stimulated with
      lipopolysaccharide plus pro-inflammatory cytokines depended on production of both
      superoxide and H2O2. Using the mitochondria-targeted chemical probe MitoSOX Red,
      we found that mitochondria-derived superoxide can act as a direct determinant of
      8-nitro-cGMP formation. Furthermore, we demonstrated that Nox2 (NADPH oxidase 2)
      generated H2O2 regulated mitochondria-derived superoxide production, which
      suggests the importance of cross-talk between Nox2-dependent H2O2 production and
      mitochondrial superoxide production. The results of the present study suggest
      that 8-nitro-cGMP can serve as a unique second messenger that may be implicated
      in regulating ROS signalling in the presence of NO.

PMID- 21967516
TI  - Minding matter: how not to argue for the causal efficacy of the mental.
AB  - The most fundamental issue of the neurosciences is the question of how or whether
      the mind and the body can interact with each other. It has recently been
      suggested in several studies that current neuroimaging evidence supports a view
      where the mind can have a well-documented causal influence on various brain
      processes. These arguments are critically analyzed here. First, the metaphysical
      commitments of the current neurosciences are reviewed. According to both the
      philosophical and neuroscientific received views, mental states are necessarily
      neurally based. It is argued that this leaves no room for a genuine interaction
      of the mental and the neural. Second, it is shown how conclusions drawn from
      recent imaging studies are in fact compatible with the fully physicalistic notion
      of mental causation and how they can thus be easily accommodated to the received
      view. The fallacious conclusions are argued to be a result of an overly vague
      grasping of the conceptual issues involved. The question of whether the
      fundamental physical principles exclude outright the ability of mental states to
      have causal influence on the physical world is also addressed and the reaction of
      appealing to the apparent loophole provided by quantum physics is assessed. It is
      argued that linking psychology to quantum physics contradicts many basic tenets
      of the current neurosciences and is thus not a promising line of study. It is
      concluded that the interactionist hypothesis benefits from neither conceptual nor
      empirical support.

PMID- 21967518
TI  - The neurobiology of intertemporal choice: insight from imaging and lesion
      studies.
AB  - People are frequently faced with intertemporal choices, i.e., choices differing
      in the timing of their consequences, preferring smaller rewards available
      immediately over larger rewards delivered after a delay. The inability to forgo
      sooner gratification to favor delayed reward (e.g., impulsivity) has been related
      to several pathological conditions characterized by poor self-control, including
      drug addiction and obesity. Comparative and functional human studies have
      implicated a network of brain areas involved in intertemporal choice, including
      the medial portion of the orbitofrontal cortex (mOFC). Moreover, damage to this
      cortical area increases preference for immediate gratification in intertemporal
      decisions. Here, we review recent neuroscientific studies concerning
      intertemporal choice, suggesting that the mOFC contributes to preference for
      delayed rewards, either by computing the value of future outcomes (i.e.,
      valuation), or by enabling people to imagine and represent future rewards and
      their consequences (e.g., prospection).

PMID- 21967519
TI  - Autonomic responses to pain in aging and dementia.
AB  - Increasing age and dementia are accompanied by an increased risk for
      undertreatment of pain owing to difficulty in assessing pain. Registration of
      autonomic responses to pain may contribute to a more reliable pain assessment.
      The aim of this review was to gain more insight into autonomic responses to pain
      in older persons with and without dementia. Literature searches were performed in
      the online databases MEDLINE and Web of Science. Seven studies on autonomic
      responses to pain in older people with or without dementia were included in the
      review. Autonomic responses to pain are present in older people with and without
      dementia, although they may be attenuated. Because no distinction could be made
      between different dementia subtypes based on these studies, predictions of
      changes in autonomic responses to pain have been made based on neuropathological
      changes. It can be concluded that autonomic responses to pain are attenuated in
      older people with and without dementia. Studies to specify the changes in the
      different autonomic responses for the different dementia subtypes are needed.

PMID- 21967520
TI  - Column theme: Groundwater research and training.

PMID- 21967517
TI  - Structural and synaptic plasticity in stress-related disorders.
AB  - Abstract   Stress can have a lasting impact on the structure and function of
      brain circuitry that results in long-lasting changes in the behavior of an
      organism. Synaptic plasticity is the mechanism by which information is stored and
      maintained within individual synapses, neurons, and neuronal circuits to guide
      the behavior of an organism. Although these mechanisms allow the organism to
      adapt to its constantly evolving environment, not all of these adaptations are
      beneficial. Under prolonged bouts of physical or psychological stress, these
      mechanisms become dysregulated, and the connectivity between brain regions
      becomes unbalanced, resulting in pathological behaviors. In this review, we
      highlight the effects of stress on the structure and function of neurons within
      the mesocorticolimbic brain systems known to regulate mood and motivation. We
      then discuss the implications of these spine adaptations on neuronal activity and
      pathological behaviors implicated in mood disorders. Finally, we end by
      discussing recent brain imaging studies in human depression within the context of
      these basic findings to provide insight into the underlying mechanisms leading to
      neural dysfunction in depression.

PMID- 21967521
TI  - Antisense oligonucleotide induced dystrophin exon 45 skipping at a low half
      maximal effective concentration in a cell-free splicing system.
AB  - Antisense oligonucleotides (AOs) can facilitate the expression of internally
      deleted dystrophin in dystrophin-deficient Duchenne muscular dystrophy (DMD) by
      correcting the reading frame of the pre-mRNA with AO-mediated exon skipping. An
      antisense 18-mer 2'-O-methyl RNA/ethylene-bridged nucleic acid chimera AO
      targeting exon 45 of the dystrophin gene, AO85, can induce exon 45 skipping
      efficiently in cultured cells. AO85 is expected to facilitate dystrophin
      expression in 8%-9% of all DMD patients. Here, we examined the kinetics of AO85
      mediated exon 45 skipping in a cell-free splicing system. In vitro transcribed
      pre-mRNAs containing dystrophin exon 45 and part of its flanking introns within a
      hybrid minigene were incubated with HeLa cell nuclear extract, and the resultant
      mRNAs were amplified by semiquantitative reverse transcriptase-polymerase chain
      reaction. Time-course analysis revealed that the splicing process fitted well to
      first order kinetics. Addition of AO85 produced an extra spliced product,
      deleting exon 45 (Deltaexon 45), indicating AO85-mediated exon 45 skipping.
      Production of Deltaexon 45 increased linearly with increasing concentrations of
      AO85, reaching a maximum of nearly 80% of the transcripts. The half-maximal
      effective concentration (EC(50)) of AO85 was 58.0 nM. The percentage of Deltaexon
      45 among the transcripts decreased inversely with the pre-mRNA concentration;
      Lineweaver-Burk plotting revealed a competitive fashion of AO85 action. The low
      EC(50) indicates high potential of AO85 for clinical application.

PMID- 21967522
TI  - Anaplastic large cell lymphoma: an unusual presentation in a 7-year-old girl.
AB  - Anaplastic large cell lymphoma (ALCL) accounts for 10% to 30% of all childhood
      lymphomas and approximately 5% of all non-Hodgkin's lymphoma. ALCL is considered
      to be a T-cell non-Hodgkin's lymphoma that can be divided into two major groups
      with distinct genetic, immunophenotypic, and clinical behaviors. The first group
      consists of a spectrum of CD30+ T-cell lymphoproliferative disorders that include
      primary cutaneous ALCL (C-ALCL) and lymphomatoid papulosis. The second group is
      systemic ALCL (S-ALCL), which is further divided into two subgroups: anaplastic
      lymphoma kinase positive (ALK+) and ALK-negative. Between 30% and 60% of S-ALCL
      express ALK, which is usually the result of a t(2;5) translocation that
      correlates with onset in the first three decades of life, male predominance, and
      good prognosis. Although morphologically similar, ALK- ALCL shows varied clinical
      behaviors and immunophenotypes; is commonly seen in older age groups, with a peak
      incidence in the sixth decade of life with no preference as to sex; and has an
      overall poorer prognosis. We present a case of CD30+, ALK- S-ALCL in a 7-year-old
      girl.

PMID- 21967523
TI  - Glutathione S-transferase genotype is associated with sensitivity to psoralen
      ultraviolet A photochemotherapy.
AB  - BACKGROUND: There is marked interpatient variation in responses to psoralen
      ultraviolet A (PUVA) photochemotherapy. Identification of molecular biomarkers of
      PUVA sensitivity may facilitate treatment predictability.The glutathione S
      transferases (GSTs) influence cutaneous defence against UV radiation-induced
      oxidative stress and are therefore candidate biomarkers of PUVA sensitivity.
      Several human GSTs, including GSTM1 and GSTT1, are polymorphic, and null
      polymorphisms have been associated with increased UVB erythemal sensitivity and
      skin cancer risk. PUVA also increases skin cancer risk. OBJECTIVES: To
      investigate the effect of GST genotype on PUVA sensitivity. METHODS: We
      investigated GST genotype in patients starting PUVA (n=111) and the effects of 8
      methoxypsoralen (8-MOP) on antioxidant response element (ARE)-regulated gene
      expression in mammalian cells. RESULTS: Lower minimal phototoxic doses (MPD)
      (P=0.022) and higher serum 8-MOP concentrations (P=0.052) were seen in GSTM1-null
      allele homozygotes compared with patients with one or two active alleles. In a
      subset of patients with psoriasis (n=50), the GSTM1 genotype was not associated
      with PUVA outcomes, although MPD [hazard ratio (HR) 1.37; 95% confidence interval
      (CI) for HR 1.15-1.64] and GSTT1-null (HR 2.39; 95% CI for HR 1.31-4.35) and
      GSTP1b (HR 1.96; 95% CI for HR 1.10-3.51) genotypes were associated with
      clearance of psoriasis in this patient group. Exposure of mammalian cells to 8
      MOP induced gene expression via the ARE, a regulatory sequence in promoters of
      cytoprotective genes including GSTs, suggesting that these genes may be
      implicated in 8-MOP metabolism. CONCLUSION: The polymorphic human GSTs are
      associated with PUVA sensitivity. Further studies are required to examine the
      clinical relevance of these preliminary findings.

PMID- 21967524
TI  - In vitro characterization of the alpha-thalassemia point mutation HBA2:c.95+1G>A
      [IVS-I-1(G>A) (alpha2)].
AB  - The alpha-thalassemias are a group of disorders occurring as a result of
      decreased synthesis of alpha-globin chains, most commonly due to deletions of
      alpha-globin genes. Detection of alpha-thalassemia (alpha-thal) caused by point
      mutations has increased during the past few years and more than 70 different
      point mutations have been reported for the alpha1- and alpha2-globin genes. The
      mutation at the splice donor site of the first intervening sequence [IVS-I-1
      (G>A)] of the alpha2-globin gene, HBA2:c.95+1G>A, is thought to cause a
      thalassemic phenotype by interfering with and preventing the normal splicing of
      pre-mRNA. We developed an in vitro expression system to study alpha-globin gene
      point mutations at the molecular and cellular levels. The expression vector
      carrying the HBA2:c.95+1G>A mutation (alpha2G(IVS-I-1G>A)) was created using site
      directed mutagenesis of a wild type (WT) construct of the alpha2-globin gene
      (alpha2G(2034WT)). Gene expression experiments in human bladder carcinoma 5637
      cells were carried out using sequence verified WT and mutated clones.
      Complementary DNA synthesis and polymerase chain reaction (PCR) analysis showed
      normal alpha2-globin transcripts from cells transfected with the WT vector, but
      aberrant transcripts from cells transfected with the mutated vector carrying the
      splice donor site mutation. In the presence of the G>A mutation, normal splicing
      does not occur, and a cryptic splice site 49 bp upstream of the normal site is
      used. The translation of this product produces a premature termination codon,
      thus resulting in a thalassemic phenotype.

PMID- 21967525
TI  - Structural transition in the surfactant layer that surrounds gold nanorods as
      observed by analytical surface-enhanced Raman spectroscopy.
AB  - Surface-enhanced Raman spectroscopy (SERS) of gold nanorods in
      cetyltrimethylammonium bromide solution has been used to analyze the interfacial
      surfactant structure based on the distance-dependent electromagnetic enhancement.
      The spectra were consistent with a surfactant bilayer oriented normal to the
      surface. As the surfactant concentration was reduced, a structural transition in
      the surfactant layer was observed through a sudden increase in the signal from
      the alkane chains. The structural transition was shown to influence the
      displacement of the surfactant layer by thiolated poly(ethylene glycol). The
      monodisperse and thoroughly characterized gold nanorod samples yield consistent
      enhancement factors that were compared to electromagnetic simulations.

PMID- 21967526
TI  - The relationship of microaggressions with alcohol use and anxiety among ethnic
      minority college students in a historically White institution.
AB  - Little is known about how microaggressions may impact the health and mental
      health of college students of color attending historically White universities. In
      this study, students provided self-report of the number of racial and ethnic
      microaggressions they had experienced over the previous month, as well as data on
      anxiety symptoms (Beck Anxiety Inventory), alcohol consumption (Daily Drinking
      Questionnaire) and consequences (Rutgers Alcohol Problem Index), and self
      efficacy to cope with daily hassles (General Self-efficacy Scale) and with high
      risk drinking situations (Situational Confidence Questionnaire). As expected,
      students of color reported significantly more microaggressions than their
      European American counterparts. Microaggressions and self-efficacy were
      significantly associated with anxiety (Full Model R2 = .20; p < .001),
      microaggressions and self-efficacy were significantly associated with binge
      drinking (Full Model R2 = .10; p < .01), and microaggressions, binge drinking
      events, self-efficacy, and microaggressions * self-efficacy interaction were
      significantly associated with alcohol related consequences (Full Model R2 = .28;
      p < .001) among the students of color. Results suggest that microaggressions may
      represent a health and mental health risk to students of color. Implications of
      study results and future research directions are discussed.

PMID- 21967528
TI  - A prophylactic effect of an oligodeoxynucleotide containing a cytidine-guanosine
      motif against Japanese cedar pollen-induced T-helper type 2 allergic response.
AB  - BACKGROUND: Over 10% of entire population in Japan suffer from allergic diseases
      induced by Japanese cedar pollen (JCP) every spring. In terms of preventive
      medicine, it has become a matter of urgency to establish successful prophylactic
      and therapeutic strategies for controlling the disorders. The effect of an
      oligodeoxynucleotide containing a cytidine-guanosine motif (CpG ODN) on the
      regulation of immune responses induced by JCP was investigated in this study.
      METHODS: BALB/c mice were inoculated with CpG ODN intraperitoneally before
      intranasal sensitization to JCP. Cellular infiltration in the lung of BALB/c mice
      after treatment with CpG ODN or JCP was performed by hematoxylin and eosin (H&E)
      staining. Antibody titers and cytokines levels were determined by ELISA. RESULTS:
      Intranasal inoculation of BALB/c mice with JCP induced a T-helper type 2 (Th2
      type) dominant immune response, as characterized by the production of interleukin
      (IL)-4 and IL-5 in the lung and of JCP-specific IgE antibody in serum. Prior
      intraperitoneal administration of CpG ODN to mice suppressed the subsequent JCP
      induced antibody production and infiltration of inflammatory cells in the lung.
      The inhibitory mechanism of CpG ODN seemed to be attributable to a CpG ODN
      induced Th1-type dominant environment, which down-regulated Th2-type response
      subsequently induced by JCP allergen sensitization. Furthermore, administration
      with CpG ODN decreased the production of JCP-induced IL-17, which has been found
      to play a pivotal role in several inflammatory diseases including allergic
      asthma. The decreased production of IL-17, together with reduced secretion of IL
      4 and IL-5, may contribute to diminish the inflammation in the lung of JCP
      sensitized mice. CONCLUSION: This work provides evidence that the CpG ODN has a
      prophylactic effect on the JCP-induced Th2-type allergic responses by
      establishing or restoring a Th1-type shift of immune environments.

PMID- 21967527
TI  - Perception of racial discrimination and psychopathology across three U.S. ethnic
      minority groups.
AB  - To examine the association between the perception of racial discrimination and
      the lifetime prevalence rates of psychological disorders in the three most common
      ethnic minorities in the United States, we analyzed data from a sample consisting
      of 793 Asian Americans, 951 Hispanic Americans, and 2,795 African Americans who
      received the Composite International Diagnostic Interview through the
      Collaborative Psychiatric Epidemiology Studies. The perception of racial
      discrimination was associated with the endorsement of major depressive disorder,
      panic disorder with agoraphobia, agoraphobia without history of panic disorder,
      posttraumatic stress disorder, and substance use disorders in varying degrees
      among the three minority groups, independent of the socioeconomic status, level
      of education, age, and gender of participants. The results suggest that the
      perception of racial discrimination is associated with psychopathology in the
      three most common U.S. minority groups.

PMID- 21967529
TI  - Analysis for voltammetric responses of molecular-solid tetrathionaphthalene
      confined on an electrode.
AB  - The cyclic voltammetry (CV) of solid-state tetrathionaphthalene (TTN; particles
      with diameters from a few tens to hundreds of nanometers) confined on electrodes
      was analyzed quantitatively by considering the inert-zone potential, the
      thermodynamic and kinetic interactions, and the kinetics of the electrode
      reaction. Theoretical treatments are applied for clarifying the experimentally
      accessible corresponding parameters. From the potential of full peak width at
      half-height current (DeltaE(p1/2)) and the peak current (i(p)) for the reversible
      CV voltammogram obtained at the slowest potential scan rate, the thermodynamic
      attraction forces in their active materials are evaluated as W = 3.67 +/- 0.30 kJ
      mol(-1) for the (TTN)(0/1+) redox couple. From the shift of peak potential
      (DeltaE(p)) and the changes in DeltaE(p1/2) and/or the magnitude of i(p) for the
      irreversible CV obtained against the moderate potential scan rate, the value of
      the formal rate constant (k degrees ') regarding surface electrode reaction of
      the (TTN)(0/1+) couple was evaluated as 0.59 +/- 0.10 s(-1). The interaction
      parameters of W and DeltaW[symbol: see text] being related to the thermodynamic
      and the kinetic interactions of the electrode reaction for the (TTN)(0/1+) couple
      were also evaluated as 3.39 +/- 0.41 kJ mol(-1) and -1.39 +/- 0.31 kJ mol(-1),
      respectively, from analysis for the irreversible CV.

PMID- 21967531
TI  - The 6-min walk test: responses in healthy Canadians aged 45 to 85 years.
AB  - We sought to describe responses to the 6-min walk test (6MWT) in healthy Canadian
      adults in order to facilitate interpretation of its results in patient
      populations. Seventy-seven healthy Canadians aged 45 to 85 years (65 +/- 11
      years, 40 females) completed this study. During a single visit, three 6MWTs were
      undertaken. The main outcome measure was 6-min walk distance (6MWD). Age, gender,
      height, and weight were recorded. In 61 (79%) participants, cardiorespiratory
      variables were collected during the third 6MWT using a calibrated portable gas
      analysis system. The 6MWD increased between the first and second test (615 +/- 96
      to 639 +/- 98 m; p < 0.001) with no further improvement on the third test (638 +/
      99 m; p = 0.945). The best 6MWD from the first 2 tests was 640 +/- 99 m (range
      416 to 880 m). A greater 6MWD was achieved by males compared with females (672 +/
      94 vs. 611 +/- 93 m; p = 0.005). The following equation accounted for 49% of the
      variance in 6MWD: 6MWD = 970.7 + (-5.5 * age) + (56.3 * gender), where females =
      0, males = 1. The 6MWT elicited large cardiorespiratory responses with minimal
      symptoms. The rate of oxygen uptake measured at test-end was associated with the
      6MWD (r = 0.802; p < 0.001). These data allow the 6MWD achieved in Canadian
      adults to be expressed as a percentage of the predicted value and provide
      researchers and clinicians with values for the expected cardiorespiratory
      responses in a healthy adult population for the purpose of comparison with
      patient populations.

PMID- 21967530
TI  - Beyond cue reactivity: blunted brain responses to pleasant stimuli predict long
      term smoking abstinence.
AB  - Identifying addicts with higher risk of relapse would provide the opportunity to
      implement individualized interventions and increase cessation success rates.
      Unfortunately, the ability to predict the long-term success of drug cessation
      treatments continues to elude researchers. We tested whether brain responses to
      emotional and cigarette-related pictures were predictive of the ability to
      abstain from smoking. Smokers interested in quitting (n=180) participated in a
      smoking cessation clinical trial. Before the initiation of any treatment, we
      recorded event-related potentials (ERPs) evoked by emotional (both pleasant and
      unpleasant), neutral, and cigarette-related images. Cluster analysis was used to
      assign smokers to two groups based on the amplitude of the late positive
      potential (LPP) to the experimental stimuli. While both groups showed enhanced
      responses to cigarette-related cues, one group (n=81) also showed blunted brain
      responses to intrinsically pleasant stimuli. Smokers in the latter group were
      significantly less likely to be abstinent at 10, 12 and 24 weeks after their quit
      date. In conclusion, using ERPs, a direct measure of brain activity, we found
      that smokers with blunted brain responses to intrinsically pleasant stimuli had
      lower rates of long-term smoking abstinence. This response offers a new biomarker
      for identifying smokers at higher risk of relapse and for testing the efficacy of
      new interventions aimed at normalizing brain reward systems' responses to
      intrinsically pleasant stimuli.

PMID- 21967532
TI  - Cowardice in the face of desperation: the risks of failing to pursue novel
      neuromodulation therapies.

PMID- 21967534
TI  - Incidence and avoidance of neurologic complications with paddle type spinal cord
      stimulation leads.
AB  - INTRODUCTION:   While reference is frequently made to the risk of spinal cord or
      nerve root injury with the surgical implantation of paddle type spinal cord
      stimulation (SCS) electrodes, data are lacking on the frequency, causes, and
      prevention of these complications. METHODS:   To determine the incidence and
      frequency of neurologic complications, we performed 1) a comprehensive analysis
      of the literature to determine the incidence of complications that have caused or
      could lead to neurologic injury; 2) an analysis of the US Food and Drug
      Administration Manufacturer and User Facility Device Experience (MAUDE) data
      base; and 3) an investigation of manufacturers' data on surgically implanted
      paddle electrodes. We then convened an expert panel of neurosurgeons experienced
      in the surgical implantation of paddle electrodes to provide recommendations to
      minimize the risk of neurologic injury. RESULTS:   The scientific literature
      describes the breadth of neurologic complications that can result from SCS
      electrode implantation but does not provide interpretable data with respect to
      the incidence and frequency of these complications. The MAUDE data base is not
      constructed to be sensitive or specific enough to provide these critical data.
      Primary data show a risk of neurologic injury from implantation of paddle
      electrodes below 0.6%. DISCUSSION:   Preoperative, intraoperative, and
      postoperative measures to further minimize this risk are described. CONCLUSIONS: 
      This investigation, the first comprehensive evaluation of the incidence and
      frequency of neurologic injury as a result of SCS paddle electrode implantation,
      suggests that neurologic injury is a rare, but serious, complication of SCS. The
      incidence of these complications should be decreased by the adoption of
      approaches that improve procedural safety and by careful patient follow-up and
      complication management. Physicians should be aware of these approaches and take
      every precaution to reduce the risk of neurologic injury. Physicians also should
      report any adverse event leading to injury or death and work together to improve
      access to these data.

PMID- 21967535
TI  - Post hoc ergo propter hoc?

PMID- 21967536
TI  - Peripheral neuromodulation for angina: gathering momentum.

PMID- 21967539
TI  - Nanomolar binding of peptides containing noncanonical amino acids by a synthetic
      receptor.
AB  - This paper describes the molecular recognition of phenylalanine derivatives and
      their peptides by the synthetic receptor cucurbit[7]uril (Q7). The 4-tert-butyl
      and 4-aminomethyl derivatives of phenylalanine (tBuPhe and AMPhe) were identified
      from a screen to have 20-30-fold higher affinity than phenylalanine for Q7.
      Placement of these residues at the N-terminus of model tripeptides (X-Gly-Gly),
      resulted in no change in affinity for tBuPhe-Gly-Gly, but a remarkable 500-fold
      increase in affinity for AMPhe-Gly-Gly, which bound to Q7 with an equilibrium
      dissociation constant (K(d)) value of 0.95 nM in neutral phosphate buffer.
      Structure-activity studies revealed that three functional groups work in a
      positively cooperative manner to achieve this extraordinary stability (1) the N
      terminal ammonium group, (2) the side chain ammonium group, and (3) the peptide
      backbone. Addition of the aminomethyl group to Phe substantially improved the
      selectivity for peptide versus amino acid and for an N-terminal vs nonterminal
      position. Importantly, Q7 binds to N-terminal AMPhe several orders of magnitude
      more tightly than any of the canonical amino acid residues. The high affinity,
      single-site selectivity, and small modification in this system make it attractive
      for the development of minimal affinity tags.

PMID- 21967540
TI  - Coarticulation in early vocalizations by children with hearing loss: a locus
      perspective.
AB  - Locus equations derived from productions by three children with hearing loss
      revealed sensory and motor influences on anticipatory coarticulation.
      Participants who received auditory access to speech via hearing aids and cochlear
      implants at different ages (5-39 months) were recorded at approximately 6 and 12
      months after hearing technology fitting. One was also recorded 1 month pre
      implantation. Locus equations were compared with data from typically developing
      children: (1) chronological age peers, and (2) peers with equivalent duration of
      audition, or hearing age. Anticipatory coarticulation followed typical trajectory
      in the child fit with hearing aids at 5 months. Anticipatory coarticulation by
      children with profound hearing loss using cochlear implants was closer to
      typically developing children with the same chronological age in syllables
      present pre-implantation and closer to children with equivalent hearing age in
      syllables emerging post-implantation. Results are discussed regarding
      interactions among sensory input, general motor development and specific motor
      experience.

PMID- 21967541
TI  - NAADP regulates human platelet function.
AB  - Platelets play a vital role in maintaining haemostasis. Human platelet activation
      depends on Ca2+ release, leading to cell activation, granule secretion and
      aggregation. NAADP (nicotinic acid-adenine dinucleotide phosphate) is a Ca2+
      releasing second messenger that acts on acidic Ca2+ stores and is used by a
      number of mammalian systems. In human platelets, NAADP has been shown to release
      Ca2+ in permeabilized human platelets and contribute to thrombin-mediated
      platelet activation. In the present study, we have further characterized NAADP
      mediated Ca2+ release in human platelets in response to both thrombin and the
      GPVI (glycoprotein VI)-specific agonist CRP (collagen-related peptide). Using a
      radioligand-binding assay, we reveal an NAADP-binding site in human platelets,
      indicative of a platelet NAADP receptor. We also found that NAADP releases loaded
      45Ca2+ from intracellular stores and that total platelet Ca2+ release is
      inhibited by the proton ionophore nigericin. Ned-19, a novel cell-permeant NAADP
      receptor antagonist, competes for the NAADP-binding site in platelets and can
      inhibit both thrombin- and CRP-induced Ca2+ release in human platelets. Ned-19
      has an inhibitory effect on platelet aggregation, secretion and spreading. In
      addition, Ned-19 extends the clotting time in whole-blood samples. We conclude
      that NAADP plays an important role in human platelet function. Furthermore, the
      development of Ned-19 as an NAADP receptor antagonist provides a potential avenue
      for platelet-targeted therapy and the regulation of thrombosis.

PMID- 21967542
TI  - The Second Stroke Audit of Catalonia shows improvements in many, but not all
      quality indicators.
AB  - BACKGROUND: Periodic audits allow monitoring of healthcare quality by comparing
      performances at different time points. Aims To assess quality of in-hospital
      stroke care in Catalonia in 2007 and compare it with 2005 (post-/preguidelines
      delivery, respectively). METHODS: Data on 13 evidence-based performance measures
      were collected by a retrospective review of medical records of consecutive stroke
      admissions (January-December 2007) to 47 acute hospitals in Catalonia. Adherence
      was calculated according to the ratio (patients with documented performance
      measures' compliance) (valid cases for that measure). Sampling weights were
      applied to produce estimates of compliance. The proportions of compliance with
      performance measures in both audits were compared using random-effects logistic
      regressions, with each performance measure as the dependent variable and audit
      edition as the explanatory variable to determine whether changes in stroke care
      quality occurred along time. RESULTS: We analyzed 1767 events distributed among
      47 hospitals. In 2007, there was an increase in tissue plasminogen activator
      administrations (2.8% vs. 5.9%) and stroke unit admissions (16.6% vs. 22.6%) and
      a reduction in seven-day mortality (9.5% vs. 6.8%). Logistic regression models
      provided evidence of improved adherences to seven performance measures (screening
      of dysphagia, management of hyperthermia, baseline computed tomography scan,
      baseline glycemia, rehabilitation needs, early mobilization, and anticoagulants
      for atrial fibrillation), but worsening of management of hypertension,
      dyslipidemia, and antithrombotics at discharge. The remaining three performance
      measures showed no changes. CONCLUSIONS: The Second Stroke Audit showed
      improvements in most dimensions of care, although unexpectedly a few but relevant
      performance measures became worse. Therefore, periodic stroke audits are needed
      to check changes in quality of care over time.

PMID- 21967543
TI  - Exchange of a tandem heart to a HeartMate II left ventricular assist device
      complicated by an intracardiac thrombus.

PMID- 21967544
TI  - Physicochemical insights on the free radical scavenging activity of sesamol:
      importance of the acid/base equilibrium.
AB  - Reactions of sesamol with different free radicals, in lipid and aqueous media,
      have been studied at the M05-2X/6-311+G(d,p) level of theory in conjunction with
      the SMD continuum model. Different mechanisms of reaction have been considered as
      well as polar and nonpolar environments. According to the overall rate
      coefficients, sesamol is predicted to react significantly faster in aqueous
      solution than in nonpolar media. The polarity of the environment also changes the
      relative importance of the reaction mechanisms. The anionic form of sesamol was
      found to be particularly reactive toward peroxyl radicals by transferring one
      electron. This mechanism was found responsible for the exceptional peroxyl
      radical scavenging activity of sesamol in aqueous solution, which was found to be
      even better than carotenoids, 2-propenesulfenic acid, and glutathione under
      physiological conditions. The agreement between experimental and calculated data
      supports the presented results as well as the methodology used in this work.

PMID- 21967545
TI  - Thermal drawing of high-density macroscopic arrays of well-ordered sub-5-nm
      diameter nanowires.
AB  - We investigate the lower limit of nanowire diameters stably produced by the
      process of thermal fiber drawing and fiber tapering. A centimeter-scale
      macroscopic cylindrical preform containing the nanowire material in the core
      encased in a polymer scaffold cladding is thermally drawn in the viscous state to
      a fiber. By cascading several iterations of the process, continuous reduction of
      the diameter of an amorphous semiconducting chalcogenide glass is demonstrated.
      Starting from a 10-mm-diameter rod we thermally draw hundreds of meters of
      continuous sub-5-nm-diameter nanowires. Using this approach, we produce
      macroscopic lengths of high-density, well-ordered, globally oriented nanowire
      arrays.

PMID- 21967546
TI  - Prognostic impact of DNMT3A mutations in patients with intermediate cytogenetic
      risk profile acute myeloid leukemia.
AB  - OBJECTIVES: Recently, mutations in DNMT3A gene have been described in about 25%
      acute myeloid leukemia (AML) cases, preferentially in monocytic AML. They were
      found to predict worse overall survival (OS) of mutated patients. PATIENTS AND
      METHODS: RT-PCR followed by direct sequencing was used to test the presence of
      DNMT3A mutations in 226 AML patients with an intermediate-risk (IR) cytogenetics.
      RESULTS: Sixty-seven patients of 226 (29.6%) carried a mutation in the DNMT3A
      gene. Occurrence of DNMT3A mutations was associated with female sex (P = 0.027)
      and with the presence of FLT3/ITD (P = 0.003), but not with particular FAB
      subtypes. Patients with DNMT3A mutation had higher initial WBC counts than those
      without it (P = 0.064) only because of higher incidence of FLT3/ITD within these
      cases. There was no difference between mutated and wild-type groups in reaching
      complete remission (CR) (P = 0.380). OS was not affected by DNMT3A mutation (P =
      0.251), but OS of patients who reached CR was longer in DNMT3A negative cases (P
      = 0.025). Patients with DNMT3A mutation had a higher relapse rate (P = 0.007).
      Patients carrying both the DNMT3A mutation and FLT3/ITD relapsed more often than
      either patients with single DNMT3A mutation (P = 0.044) or patients with FLT3/ITD
      only (P = 0.058). DNMT3A mutations were associated with higher relapse rate even
      within the FLT3/ITD-negative group (P = 0.072). After reaching CR, these two
      genetic factors were independent predictors of relapse at multivariate analysis
      (P < 0.001). Only three of 30 'double-mutated' (FLT3/ITD+, DNMT3A+) patients are
      still alive, all of them having undergone hematopoietic stem cell transplant.
      CONCLUSIONS: We have confirmed the high incidence of DNMT3A mutations in patients
      with AML with IR cytogenetics. Patients with DNMT3A mutations relapse more often
      and have inferior OS when only patients achieving CR are analyzed. 'Double
      mutated' patients have a very poor prognosis.

PMID- 21967547
TI  - Meta-analysis: glutathione-S-transferase allelic variants are associated with
      alcoholic liver disease.
AB  - BACKGROUND: Only a minority of alcoholics develop alcoholic liver disease (ALD)
      and allelic variants within genes encoding glutathione-S-transferases (GST) have
      been associated with ALD vulnerability with controversial results. AIM: To assess
      the effects of GST polymorphisms on ALD by means of a genetic association study
      and meta-analysis. METHODS: We retrieved published studies on the relationship
      between allelic variants within GST genes and ALD by means of electronic database
      search. A meta-analysis was conducted in a fixed or random effects model.
      Calculations of odds ratios (OR) and their confidence intervals (CI), tests for
      heterogeneity of the results and sensitivity analysis, have been performed. A
      genetic association study comparing GSTM1, GSTT1 and GSTP1 genotype distribution
      among 279 alcoholics with or without ALD and 144 controls was also performed.
      Results  Fifteen previous studies were identified analysing the association of
      ALD with polymorphisms within GST genes. After meta-analysis, we found a
      significant association between the possession of the GSTM1 null allele and the
      presence of ALD (OR=1.43; 95% CI: 1.14, 1.78; P=0.002) among alcoholic patients.
      A significant association was also found for the possession of the GSTP1 Val/Val
      genotype and the presence of ALD (OR=2.04; 95% CI: 1.09, 3.80; P=0.03).
      CONCLUSIONS: Our results suggest that, among alcoholics, carriers of GSTM1 null
      genetic variant or Val/Val genotype of Ile/Val GSTP1 polymorphism have an
      increased risk to suffer from alcoholic liver disease. The role of glutathione-S
      transferase as a potential therapeutic target in alcoholic liver disease is
      reinforced.

PMID- 21967549
TI  - Acceptance of elective bradypacing by patients: an African perspective.
AB  - BACKGROUND: In our practice, we noticed that patients respond differently when
      pacemaker insertion is recommended to them. We then saw the need to study how
      African patients accept elective pacemaker implantation. AIM: The study was
      conducted to determine African patients' responses to elective pacemaker
      insertion. PATIENTS AND METHODS: We recruited patients who reported at our
      outpatient clinic with indications for elective pacemaker insertion. The study
      period lasted 64 months from September 1999. The patients were counseled before
      insertion and we sought their consent before being recruited for the study. Five
      possible responses were used to grade acceptance. They were followed up for 12
      months each. Patients who were brought in emergency and those who refused
      participation were excluded. Those who missed follow-up were also dropped.
      RESULTS: Ninety-two patients (n = 92) met our study criteria after dropping eight
      patients who missed follow-up clinic attendance. Most of the candidates (71.7%)
      felt they had no options but to accept pacemakers at the time of operation. The
      remaining candidates either accepted the procedure with hope or wholeheartedly.
      Most of the candidates migrated up the ladder of acceptance over the 12-month
      period. DISCUSSION AND CONCLUSION: We concluded that most patients would accept
      pacemakers wholeheartedly over time.

PMID- 21967548
TI  - Small average differences in attenuation corrected images between men and women
      in myocardial perfusion scintigraphy: a novel normal stress database.
AB  - BACKGROUND: The American Society of Nuclear Cardiology and the Society of Nuclear
      Medicine state that incorporation of attenuation-corrected (AC) images in
      myocardial perfusion scintigraphy (MPS) will improve image quality, interpretive
      certainty, and diagnostic accuracy. However, commonly used software packages for
      MPS usually include normal stress databases for non-attenuation corrected (NC)
      images but not for attenuation-corrected (AC) images. The aim of the study was to
      develop and compare different normal stress databases for MPS in relation to NC
      vs. AC images, male vs. female gender, and presence vs. absence of obesity. The
      principal hypothesis was that differences in mean count values between men and
      women would be smaller with AC than NC images, thereby allowing for construction
      and use of gender-independent AC stress database. METHODS: Normal stress
      perfusion databases were developed with data from 126 male and 205 female
      patients with normal MPS. The following comparisons were performed for all
      patients and separately for normal weight vs. obese patients: men vs. women for
      AC; men vs. women for NC; AC vs. NC for men; and AC vs. NC for women. RESULTS:
      When comparing AC for men vs. women, only minor differences in mean count values
      were observed, and there were no differences for normal weight vs. obese
      patients. For all other analyses major differences were found, particularly for
      the inferior wall. CONCLUSIONS: The results support the hypothesis that it is
      possible to use not only gender independent but also weight independent AC stress
      databases.

PMID- 21967550
TI  - Therapeutic management for post-traumatic treatment of the anterior dental
      region: a case report with long-term follow up.
AB  - The treatment plan represents the final step in every diagnostic procedure and is
      the result of a series of assessments based on information gathered from a
      detailed clinical history. This clinical case reports the replacement of two
      central incisors that were lost because of a trauma. The advantages and
      disadvantages of the two treatment options (i.e. implantology or prosthetic
      restoration) were carefully evaluated in relation to the case in hand. Patient
      compliance and aesthetic requirements had been also considered. In this case, a
      conventional prosthetic restoration was performed using a metal-ceramic bridge,
      utilising full crowns between the right and left maxillary lateral incisors
      associated with minimal canine preparation. By this strategy, the treatment plan
      allows for a future implant restoration, should this become necessary.

PMID- 21967551
TI  - Copper(II)-catalyzed asymmetric henry reaction of o-alkynylbenzaldehydes followed
      by gold(I)-mediated cycloisomerization: an enantioselective route to chiral 1H
      isochromenes and 1,3-dihydroisobenzofurans.
AB  - By combining the copper(II)-catalyzed asymmetric Henry reaction of o
      alkynylbenzaldehydes with subsequent gold(I)-catalyzed cycloisomerization,
      optically active 1H-isochromenes and 1,3-dihydroisobenzofurans were successfully
      synthesized in good overall yields with good to excellent enantioselectivities
      (up to 98%). Various substrates were investigated, and a correlation between the
      regioselectivity and electronic nature of the substrates was studied. The
      substrates with electro-donating groups at the alkynyl moiety preferred a 6-endo
      dig manner to generated 1H-isochromenes 3 as main products (up to >30:1) while
      the ones with electron-withdrawing groups were inclined to undergo 5-exo-dig
      cyclization to form 1,3-dihydroisobenzofurans 4 (up to 1:5).

PMID- 21967552
TI  - Quantitative real-time ARMS-qPCR for mitochondrial DNA enables accurate detection
      of microchimerism in renal transplant recipients.
AB  - The presence of microchimerism in peripheral blood of solid organ transplant
      recipients has been postulated to be beneficial for allograft acceptance.
      Kinetics of donor cell trafficking and accumulation in pediatric allograft
      recipients are largely unknown. In this study, we implemented SNPs of the HVRs I
      and II of mitochondrial DNA to serve as molecular genetic markers to detect donor
      specific cell chimerism after pediatric renal transplantation. Serial dilution of
      artificial chimeric DNA samples showed a linear correlation coefficient of R >
      0.98 and a detection sensitivity of 0.01% with high reproducibility. Longitudinal
      semiquantitative analysis of donor-specific SNPs was then performed in peripheral
      blood mononuclear cells samples up to two yr post-transplant. Quantity of donor
      specific cell chimerism in peripheral blood was highest in the early post
      transplant period reaching values of ~10% after liver-kidney and 2.8% after renal
      transplantation. From one wk after transplantation, renal transplant patients
      exhibited an amount of donor-specific mtDNA ranging from 0.01% to 0.1%. We
      developed a highly accurate, sensitive, and rapid real-time quantitative PCR
      method using sequence-specific primers and fluorescent hydrolysis probes for the
      detection of at least 0.01% donor-specific cells in the recipient's peripheral
      blood after renal transplantation.

PMID- 21967553
TI  - Bilateral milia en plaque in a 6-year-old Chinese boy.
AB  - Milia en plaque is a rare variant of miliathat occurs spontaneously on an
      erythematous base without identifiable causative factors. Approximately 40 cases
      have been recorded in the literature. Most occurred in the periauricular area,
      affected middle-aged patients, and showed a predilection for women. Here, we
      report a case of milia en plaque on the bilateral posterior helices in a 6-year
      old Chinese boy.

PMID- 21967554
TI  - Cognitive profile of adolescents with math disabilities: are the profiles
      different from those with reading disabilities?
AB  - Adolescents (ages 14-17) with math disabilities (MD, n=12), reading disabilities
      (RD, n=19), math+reading disabilities (MD+RD, n=12), and average achievers (n=15)
      were compared on measures of visual-spatial processing, random generation
      (inhibition), writing speed, short-term memory (STM), and working memory (WM).
      Adolescents with MD performed significantly lower than adolescents with RD on
      measures of visual-spatial processing and visual WM. Adolescents with MD
      outperformed adolescents with RD +MD on measures of random generation and motor
      speed. Performance of all three low-achieving groups was inferior to average
      achievers on measures of random generation, motor speed, and verbal WM. The
      results were interpreted within a multicomponent model that attributed deficits
      related to MD in adolescents to deficits related the visual-spatial sketchpad of
      WM.

PMID- 21967555
TI  - The fatty acid profile of the skin surface lipid layer in papulopustular rosacea.
AB  - BACKGROUND: Patients with papulopustular rosacea (PPR) frequently complain of
      dry, sensitive skin. We have previously demonstrated that patients with PPR have
      reduced skin surface hydration levels in the presence of normal sebum casual
      levels, suggesting that it may be the quality and not the quantity of sebum that
      plays a role in PPR. OBJECTIVES: To compare the sebaceous fatty acid composition
      of patients with PPR to that of controls with normal facial skin. METHODS: The
      sebaceous fatty acid composition of 25 patients with PPR and 24 age- and sex
      matched controls was analysed by gas chromatography - mass spectrometry. Results 
      Myristic acid (C14:0) was present in greater concentrations in PPR sebum, while
      the long chain saturated fatty acids arachidic acid (C20:0), behenic acid
      (C22:0), tricosanoic acid (C23:0) and lignoceric acid (C24:0) as well as the
      monounsaturated fatty acid cis-11-eicosanoic acid (C20:1) were present in the
      sebum of patients with PPR in lesser concentrations as compared with controls.
      CONCLUSIONS: There is increasing evidence that sebaceous fatty acids play a role
      in the maintenance of skin barrier integrity. We have shown for the first time
      that patients with PPR have an abnormal sebaceous fatty acid composition, with
      reduced levels of long chain saturated fatty acids. These new findings may have
      therapeutic implications for the development of sebum-modifying nonantibiotic
      treatments for patients with PPR.

PMID- 21967556
TI  - First description of a Hb A2 variant in Thailand. Identification of Hb A2
      Melbourne [delta43(CD2)Glu->Lys] in Thai individuals.
AB  - We report the molecular and hematological identifications of a Hb A(2) variant
      found for the first time in Thailand. The subjects were two unrelated Thai women
      who had normal hematological features. In the first case, hemoglobin (Hb) high
      performance liquid chromatography (HPLC) analysis identified, in addition to Hb
      A, Hb A(2) (1.6%) and a minor Hb variant (0.9%) separating after Hb A(2).
      Analysis using capillary electrophoresis (CE) demonstrated 1.3% Hb A(2) and 1.0%
      minor variant in zone 1. DNA analysis showed a single nucleotide mutation at
      codon 43 of the delta-globin gene (HBD:c.130G>A) causing a glutamic acid to
      lysine substitution corresponding to Hb A(2)-Melbourne, originally documented in
      an Italian subject, but not previously described in Thailand. The mutation could
      be confirmed by allele specific polymerase chain reaction (PCR) assay. Further
      screening using this technique in our series identified another case of a Thai
      woman with a double heterozygosity for Hb A(2)-Melbourne and alpha(+)-thalassemia
      (alpha(+)-thal). A beta-globin gene haplotype associated with this Thai Hb A(2)
      Melbourne gene was also established.

PMID- 21967557
TI  - Imidazoline receptor antisera-selected/Nischarin regulates the effect of agmatine
      on the development of morphine dependence.
AB  - Agmatine, an endogenous ligand for imidazoline receptor, has been shown to
      prevent opioid dependence, but not much is known about the mechanisms of the
      effect of agmatine. In the present study, we investigated the function of I1
      imidazoline receptor and its candidate protein imidazoline receptor antisera
      selected (IRAS)/Nischarin in morphine dependence as well as in the effect of
      agmatine inhibiting morphine dependence by pharmacological and molecular
      approaches. Results showed that inhibition of IRAS or Nischarin did not change
      the development of morphine dependence in vitro and in vivo under the basal
      condition. Agmatine could reduce the cyclic 3', 5' adenosine monophosphate (cAMP)
      overshoot at the concentration of 0.01-10 uM in the primary cultured rat
      hippocampal neurons and attenuated the withdrawal signals and the elevation of
      FosB and DeltaFosB at the dose of 5 mg/kg in the morphine-dependent mice. The
      effect of agmatine was inhibited by efaroxan (I1 imidazoline receptor non
      specific antagonist) and the RNA interference against IRAS or Nischarin. These
      findings indicate that I1 imidazoline receptor or IRAS/Nischarin mediates the
      effect of agmatine on morphine dependence and provide evidence that I1
      imidazoline receptor may be a new target for treating morphine dependence.

PMID- 21967558
TI  - Characterization of graphene grown on bulk and thin film nickel.
AB  - We report on graphene films grown by atmospheric pressure chemical vapor
      deposition on bulk and thin film nickel. Carbon precipitation on the
      polycrystalline grains is controlled by the methane concentration and substrate
      cooling rate. It is found that graphene grows over multiple grains, with edges
      terminating along the grain boundaries and with dimensions directly correlated to
      the size of the underlying grains. This greatly restricts the resulting graphene
      size (<10 MUm) in the thin film growth, whereas monolayer graphene with linear
      dimensions of hundreds of micrometers takes up the great majority of the surface
      overlayers on the bulk nickel (>50%). In addition, the number of layers can be
      better controlled in the bulk growth. Characterizations of the graphene sheets
      using transmission electron microscopy, Raman spectroscopy, and transport
      measurements in the field-effect configuration are also discussed.

PMID- 21967559
TI  - Change in ethnic identity across the college transition.
AB  - This article examined changes in ethnic identity as a function of college type
      and residential status and whether differences due to college type could be
      explained by involvement in extracurricular activities and college ethnic
      composition. Although no changes in ethnic labeling or belonging were found,
      there was a normative decrease in ethnic search, independent of residential
      status. Moreover, the decline in ethnic search was significantly greater at 2-
      than 4-year colleges, and this difference was mediated by higher rates of
      participation in extracurricular activities at 4-year colleges. Ethnic identity
      did not vary by college ethnic composition. There were no ethnic or generation
      differences in ethnic identity change; however, women were more likely to include
      an American term in their ethnic label than were men, over time. Averaging across
      time, students at 4-year colleges also had a greater preference for the American
      term in their ethnic labels. Findings illuminate the importance of context in
      shaping ethnic identity.

PMID- 21967560
TI  - Children and situation models of multiple events.
AB  - The present study demonstrates that children experience difficulties reaching the
      correct situation model of multiple events described in temporal sentences if the
      sentences encode language-external events in reverse chronological order.
      Importantly, the timing of the cue of how to organize these events is crucial:
      When temporal subordinate conjunctions (before/after) or converb constructions
      that carry information of how to organize the events were given sentence
      medially, children experienced severe difficulties in arriving at the correct
      interpretation of event order. When this information was provided sentence
      initially, children were better able to arrive at the correct situation model,
      even if it required them to decode the linguistic information reversely with
      respect to the actual language external events. This indicates that children even
      aged 8-12 still experience difficulties in arriving at the correct interpretation
      of the event structure, if the cue of how to order the events is not given
      immediately when they start building the representation of the situation. This
      suggests that children's difficulties in comprehending sequential temporal events
      are caused by their inability to revise the representation of the current event
      structure at the level of the situation model.

PMID- 21967561
TI  - Development of single/geminate obstruent discrimination by Japanese infants:
      early integration of durational and nondurational cues.
AB  - The Japanese language has single/geminate obstruents characterized by durational
      difference in closure/frication as part of the phonemic repertoire used to
      distinguish word meanings. We first evaluated infants' abilities to discriminate
      naturally uttered single/geminate obstruents (/pata/ and /patta/) using the
      visual habituation-dishabituation method. The results revealed that 9.5-month-old
      Japanese infants were able to make this discrimination, t(21) = 2.119, p = .046,
      paired t test, whereas 4-month-olds were not, t(25) = 0.395, p = .696, paired t
      test. To examine how acoustic correlates (covarying cues) are associated with the
      contrast discrimination, we tested Japanese infants at 9.5 and 11.5 months of age
      with 3 combinations of natural and manipulated stimuli. The 11.5-month-olds were
      able to discriminate the naturally uttered pair (/pata/ vs. /patta/), t(20) =
      4.680, p < .000, paired t test. Neither group discriminated the natural /patta/
      from the manipulated /pata/ created from natural /patta/ tokens: For 9.5-month
      olds, t(23) = 0.754, p = .458; for 11.5-month-olds, t(27) = 0.789, p = .437,
      paired t tests. Only the 11.5-month-olds discriminated the natural /pata/ and the
      manipulated /patta/ created from /pata/ tokens: For 9.5-month-olds, t(24) =
      0.114, p = .910; for 11.5-month-olds, t(23) = 2.244, p = .035, paired t tests.
      These results suggest that Japanese infants acquire a sensitivity to contrasts of
      single/geminate obstruents by 9.5 months of age and that certain cues that covary
      with closure length either facilitate or interfere with contrast discrimination
      under particular conditions.

PMID- 21967562
TI  - Implicit statistical learning is directly associated with the acquisition of
      syntax.
AB  - This article reports on an individual differences study that investigated the
      role of implicit statistical learning in the acquisition of syntax in children.
      One hundred children ages 4 years 5 months through 6 years 11 months completed a
      test of implicit statistical learning, a test of explicit declarative learning,
      and standardized tests of verbal and nonverbal ability. They also completed a
      syntactic priming task, which provided a dynamic index of children's facility to
      detect and respond to changes in the input frequency of linguistic structure. The
      results showed that implicit statistical learning ability was directly associated
      with the long-term maintenance of the primed structure. The results constitute
      the first empirical demonstration of a direct association between implicit
      statistical learning and syntactic acquisition in children.

PMID- 21967563
TI  - Age-related changes in decision making: comparing informed and noninformed
      situations.
AB  - Advantageous decision making progressively develops into early adulthood, most
      specifically in complex and motivationally salient decision situations in which
      direct feedback on gains and losses is provided (Figner & Weber, 2011). However,
      the factors that underlie this developmental improvement in decision making are
      still not well understood. The current study therefore investigates 2 potential
      factors, long-term memory and working memory, by assigning a large developmental
      sample (7-29 years of age) to a condition with either high or low demands on long
      term and working memory. The first condition featured an age-adapted version of
      the Iowa Gambling Task (IGT; Bechara, Damasio, Damasio, & Anderson, 1994; i.e., a
      noninformed situation), whereas the second condition provided an external store
      where explicit information on gains, losses, and probabilities per choice option
      was presented (i.e., an informed situation). Consistent with previous
      developmental IGT studies, children up to age 12 did not learn to prefer
      advantageous options in the noninformed condition. In contrast, all age groups
      learned to prefer the advantageous options in the informed conditions, although a
      slight developmental increase in advantageous decision making remained. These
      results indicate that lowering dependence on long-term and working memory
      improves children's advantageous decision making. The results additionally
      suggest that other factors, like inhibitory control processes, may play an
      additional role in the development of advantageous decision making.

PMID- 21967565
TI  - Arousing "gentle passions" in young adolescents: Sustained experimental effects
      of value affirmations on prosocial feelings and behaviors.
AB  - When people reflect on their important values, they may become more attuned to
      the needs of others. Two longitudinal field experiments examined whether a subtle
      value-affirmation manipulation can initiate relatively enduring increases in
      young adolescents' prosocial feelings (Study 1; Mage = 12.9) and prosocial
      behaviors (Study 2; Mage = 12.9). Participants completed a brief writing exercise
      that affirmed the values they deemed either most important (value-affirmation
      group) or unimportant (control group). As predicted, the value affirmation,
      coupled with a booster affirmation 6 weeks later, caused increases in prosocial
      feelings and behaviors over the 3-month study period. Antisocial students who
      were value-affirmed showed especially strong increases in prosocial behavior.
      These results suggest that "gentle passions" can be aroused in youth by cost- and
      time-efficient means. The practical utility of value affirmations will need to be
      evaluated in future work.

PMID- 21967564
TI  - A developmental-contextual model of depressive symptoms in Mexican-origin female
      adolescents.
AB  - The current study tested a developmental-contextual model of depressive
      symptomatology among Mexican-origin, female early and middle adolescents and
      their mothers. The final sample comprised 271 dyads. We examined the
      interrelations among cultural (i.e., acculturation dissonance), developmental
      (i.e., pubertal development and autonomy expectation discrepancies), and
      interpersonal (i.e., mother-daughter conflict and maternal supportive parenting)
      factors in predicting adolescents' depressive symptoms. For both early and middle
      adolescents, maternal support was negatively associated with mother-daughter
      conflict and depressive symptoms. Mother-daughter autonomy expectation
      discrepancies were positively associated with mother-daughter conflict, but this
      association was found only among early adolescents. Further, mother-daughter
      acculturation dissonance was positively associated with mother-daughter conflict
      but only among middle adolescents. Findings call for concurrently examining the
      interface of developmental, relational, and cultural factors in predicting female
      adolescents' depressive symptomatology and the potential differences by
      developmental stage (e.g., early vs. middle adolescence).

PMID- 21967566
TI  - Do other people's plights matter? A genetically informed twin study of the role
      of social context in the link between peer victimization and children's
      aggression and depression symptoms.
AB  - Using a genetically informed design, this study examined the additive and
      interactive effects of genetic risk, personal peer victimization experiences, and
      peer victimization experienced by others on children's aggression and depression
      symptoms. Of major interest was whether these effects varied depending on whether
      or not the victimized others were children's close friends. The sample comprised
      197 monozygotic and same-sex dizygotic twin pairs reared together (95 female
      pairs) assessed in Grade 4. Each twin's victimization experiences and
      victimization experienced by his or her friends and other classmates were
      measured using individuals' reports about their own levels of peer victimization.
      Aggression was assessed using peer nominations, and depression was measured using
      self-reports. Indicative of a possible social-learning mechanism or the emotional
      contagion of anger, multilevel regressions showed that personal victimization
      experiences were related to especially high levels of aggression when close
      friends where also highly victimized, albeit only in boys. Moreover, in line with
      social comparison theory, the effect of frequent personal victimization
      experiences on depressive feelings was much weaker when close friends were also
      highly victimized than when close friends were not or were only rarely
      victimized. Finally, a high level of peer victimization experienced by other
      classmates was related to a lower level of aggression in girls and boys, possibly
      because of a heightened sense of threat in classrooms where many suffer attacks
      from bullies. All of these results were independent of children's genetic risk
      for aggression or depression. Theoretical and practical implications are
      discussed.

PMID- 21967567
TI  - When do adaptive developmental mechanisms yield maladaptive outcomes?
AB  - This article discusses 3 ways in which adaptive developmental mechanisms may
      produce maladaptive outcomes. First, natural selection may favor risky strategies
      that enhance fitness on average but which have detrimental consequences for a
      subset of individuals. Second, mismatch may result when organisms experience
      environmental change during ontogeny, for instance, because they move from one
      environment to another. Third, organisms may learn about their environment in
      order to develop an appropriate phenotype; when cues indicate the environmental
      state probabilistically, as opposed to deterministically, sampling processes may
      produce mismatch. For each source of maladaptation, we present a selection of the
      relevant empirical research and illustrate how models from evolutionary biology
      can be used to make predictions about maladaptation. We also discuss what data
      can be collected to test these models in humans. Our goal is to show that
      evolutionary approaches not only yield insights into adaptive outcomes but can
      also illuminate the conditions leading to maladaptation. This perspective
      provides additional nuance to the dialectic between the developmental
      psychopathology model and evolutionary developmental psychology.

PMID- 21967568
TI  - Interparental violence, maternal emotional unavailability and children's cortisol
      functioning in family contexts.
AB  - Our goal in the present study was to examine the specificity of pathways among
      interparental violence, maternal emotional unavailability, and children's
      cortisol reactivity to emotional stressors within interparental and parent-child
      relationships. The study also tested whether detrimental family contexts were
      associated, on average, with hypocortisolism or hypercortisolism responses to
      stressful family interactions in young children. Participants included 201
      toddlers and their mothers who were from impoverished backgrounds and who
      experienced disproportionate levels of family violence. Assessments of
      interparental violence were derived from maternal surveys and interviews, whereas
      maternal emotional unavailability was assessed through maternal reports and
      observer ratings of caregiving. Salivary cortisol levels were sampled at 3 time
      points before and after laboratory paradigms designed to elicit children's
      reactivity to stressful interparental and parent-child contexts. Results
      indicated that interparental violence and the mother's emotional unavailability
      were differentially associated with children's adrenocorticol stress reactivity.
      Furthermore, these family risk contexts predicted lower cortisol change in
      response to distress. The results are interpreted in the context of risky family
      and emotional security theory conceptualizations that underscore how family
      contexts differentially impact children's physiological regulatory capacities.

PMID- 21967569
TI  - Working memory in children: tracing age differences and special educational needs
      to parameters of a formal model.
AB  - Parameters of a formal working-memory model were estimated for verbal and spatial
      memory updating of children. The model proposes interference though feature
      overwriting and through confusion of whole elements as the primary cause of
      working-memory capacity limits. We tested 2 age groups each containing 1 group of
      normal intelligence and 1 deficit group. For young children the deficit was
      developmental dyslexia; for older children it was a general learning difficulty.
      The interference model predicts less interference through overwriting but more
      through confusion of whole elements for the dyslexic children than for their age
      matched controls. Older children exhibited less interference through confusion of
      whole elements and a higher processing rate than young children, but general
      learning difficulty was associated with slower processing than in the age-matched
      control group. Furthermore, the difference between verbal and spatial updating
      mapped onto several meaningful dissociations of model parameters.

PMID- 21967570
TI  - Redox sensing by proteins: oxidative modifications on cysteines and the
      consequent events.
AB  - SIGNIFICANCE: Reactive oxygen species (ROS) are not only essential for the cell's
      normal functions, but also mediate many pathological effects. When cells
      experience oxidative stress, proteins are modulated by redox changes and
      ultimately generate novel signaling patterns. It remains elusive how proteins are
      modulated, rather than simply damaged, by ROS and then mediate the diverse
      cellular responses. RECENT ADVANCES: During the past decade, researchers
      frequently used "redox sensor" for proteins. However, the term "redox sensing"
      has not been clearly defined to date. Thiols of cysteines are subjected to
      oxidative modifications. The conformation changes and the various types of post
      translational modifications (PTMs) may result from thiol oxidation of the same
      protein or other proteins. The molecular effects of redox sensing include changes
      in protein activity, abundance, localization, and interaction with other
      biomacromolecules. CRITICAL ISSUES: We discuss the emerging concept of cysteine
      based redox sensing, emphasizing "sensing redox changes by proteins using their
      thiols." ROS are an input, and the conformation changes and/or the other PTMs
      after thiol oxidation are the output of redox sensing. Among dozens of redox
      sensing proteins listed in this article, SENP3 and caspase-9, which have been
      investigated in our work, are given particular attention. We also introduce the
      notion of biphasic and compartment-specific redox sensing by nuclear factor kappa
      B. FUTURE DIRECTIONS: Understanding chemical modifications and conformational
      changes following protein redox sensing requires more studies in mass
      spectrometry and crystallography. Redox-indicative probes in live cells and
      tissues will help monitor redox-related biological and pathological progresses.

PMID- 21967571
TI  - Chemical transfection of cells in picoliter aqueous droplets in fluorocarbon oil.
AB  - The manipulation of cells inside water-in-oil droplets is essential for high
      throughput screening of cell-based assays using droplet microfluidics. Cell
      transfection inside droplets is a critical step involved in functional genomics
      studies that examine in situ functions of genes using the droplet platform.
      Conventional water-in-hydrocarbon oil droplets are not compatible with chemical
      transfection due to its damage to cell viability and extraction of organic
      transfection reagents from the aqueous phase. In this work, we studied chemical
      transfection of cells encapsulated in picoliter droplets in fluorocarbon oil. The
      use of fluorocarbon oil permitted high cell viability and little loss of the
      transfection reagent into the oil phase. We varied the incubation time inside
      droplets, the DNA concentration, and the droplet size. After optimization, we
      were able to achieve similar transfection efficiency in droplets to that in the
      bulk solution. Interestingly, the transfection efficiency increased with smaller
      droplets, suggesting effects from either the microscale confinement or the
      surface-to-volume ratio.

PMID- 21967572
TI  - Ischemic involvement of the primary motor cortex is a prognostic factor in acute
      stroke.
AB  - BACKGROUND: The location of the primary motor cortex can be detected in healthy
      adults using the findings of 'T2 hypointensity' and the 'double layer sign' on 3
      T diffusion-weighted imaging. The aim of this study was to assess whether
      ischemic involvement of the primary motor cortex can be identified on 3 T
      diffusion-weighted imaging within six-hours after stroke onset and to evaluate
      whether this finding could predict clinical outcome three-months after ischemic
      stroke. METHODS: Sixty-five patients who had paralysis and ischemia of the
      anterior circulation underwent 3 T magnetic resonance imaging within six-hours of
      symptom onset. Follow-up MRI was obtained at 72 h. Anatomic localization and
      ischemic involvement of the primary motor cortex were evaluated on diffusion
      weighted imaging by two investigators. Ischemic involvement on the primary motor
      cortex was classified into three grades. Ischemic lesion volumes were measured.
      We compared the favorable outcomes at three-months between subjects with and
      without ischemic involvement on the primary motor cortex using the NIHSS and
      modified Rankin Scale. RESULTS: Ischemic involvement on the primary motor cortex
      was identified in 52% of patients. Interrater agreement coefficients were 0.93
      for the identification of ischemic involvement of primary motor cortex. As
      defined by scores on the modified Rankin Scale, among the patients with ischemic
      involvement of the primary motor cortex were worse than the patients without
      ischemic involvement of the primary motor cortex (P = 0.01). The mean ischemic
      lesion volume at baseline diffusion-weighted imaging was 38.7 +/- 41.7 cm(3) and
      was 89.8 +/- 93.6 cm(3) at follow-up T2-WI. Ischemic involvement on the primary
      motor cortex (odds ratio: 14.7) was a determinant for worse outcome. CONCLUSIONS:
      3T diffusion-weighted imaging can identify ischemic involvement on the primary
      motor cortex and may provide useful information for predicting outcome during the
      hyperacute stage. Ischemic involvement on the primary motor cortex has a
      significant negative impact on recovery.

PMID- 21967573
TI  - Stepwise proteolytic activation of type I procollagen to collagen within the
      secretory pathway of tendon fibroblasts in situ.
AB  - Proteolytic cleavage of procollagen I to collagen I is essential for the
      formation of collagen fibrils in the extracellular matrix of vertebrate tissues.
      Procollagen is cleaved by the procollagen N- and C-proteinases, which remove the
      respective N- and C-propeptides from procollagen. Procollagen processing is
      initiated within the secretory pathway in tendon fibroblasts, which are adept in
      assembling an ordered extracellular matrix of collagen fibrils in vivo. It was
      thought that intracellular processing was restricted to the TGN (trans-Golgi
      network). In the present study, brefeldin A treatment of tendon explant cultures
      showed that N-proteinase activity is present in the resulting fused ER
      (endoplasmic reticulum)-Golgi compartment, but that C-proteinase activity is
      restricted to the TGN in embryonic chick tendon fibroblasts. In late embryonic
      and postnatal rat tail and postnatal mouse tail tendon, C-proteinase activity was
      detected in TGN and pre-TGN compartments. Preventing activation of the
      procollagen N- and C-proteinases with the furin inhibitor Dec-RVKR-CMK (decanoyl
      Arg-Val-Lys-Arg-chloromethylketone) indicated that only a fraction of
      intracellular procollagen cleavage was mediated by newly activated proteinases.
      In conclusion, the N-propeptides are removed earlier in the secretory pathway
      than the C-propeptides. The removal of the C-propeptides in post-Golgi
      compartments most probably indicates preparation of collagen molecules for fibril
      formation at the cell-matrix interface.

PMID- 21967574
TI  - Achalasia secondary to neoplasia: a disease with a changing differential
      diagnosis.
AB  - Achalasia secondary to neoplasia is an uncommon entity, but recognition is
      paramount given the concern of missing a cancer diagnosis. Most case series of
      secondary achalasia occurred in prior decades raising the question of whether the
      underlying neoplastic causes have changed. All cases of achalasia secondary to
      neoplasia were reviewed at the Mayo Clinic from 2000 to the present. Cases were
      assessed for underlying cause of achalasia, whether achalasia was the primary
      presentation and demographic and clinical factors. Seventeen patients with
      achalasia secondary to neoplasia were identified. This was 1.5% of all patients
      with achalasia seen. The most common causes were adenocarcinoma of the esophagus,
      followed by breast and non-small cell lung cancer. No cases of gastric cancer
      were identified. Most patients had weight loss and rapid onset of symptoms but
      could not clearly be distinguished from primary achalasia. Nine patients
      presented with achalasia, whereas eight patients had known neoplasia. Five of
      these patients had a positive paraneoplastic panel suggestive of a paraneoplastic
      syndrome. Prognosis was generally poor except for patients with esophageal
      leiomyomatosis. This case series demonstrates a changing differential diagnosis
      for achalasia secondary to neoplasia with a higher number of patients presenting
      with a known primary and with a paraneoplastic syndrome. Awareness of secondary
      achalasia and its differentiation from primary causes is still essential.

PMID- 21967575
TI  - A population-based study of health service deficits for US adults with asthma.
AB  - OBJECTIVE: Asthma prevalence in the United States is higher than it is in many
      other countries and its impact in terms of healthcare expenditures and morbidity
      and mortality is staggering. In the United States, many groups bear a
      disproportionate burden of asthma. Understanding the epidemiology of adult asthma
      and deficits in health care can identify opportunities for improving care and
      effectively managing resources. METHODS: The computed dependent variable, health
      service deficits, entails a lack of health insurance, not having a healthcare
      provider, deferring medical care because of cost, and having had no routine
      medical exam. Bivariate and multivariate analyses were performed on 2005
      Behavioral Risk Factor Surveillance Survey data to examine the relationship
      between health service deficits experienced by adults with asthma and
      socioeconomic status (SES), race and ethnicity, and geographic locale. The
      variable was also calculated for each US state. RESULTS: Hispanic (OR = 1.594,
      95% CI = 1.588-1.599) and Other/Multiracial (OR = 1.447, 95% CI = 1.441-1.452)
      adults with current asthma had greater odds of having a health service deficit.
      Rural adults with current asthma had greater odds of having a health service
      deficit (OR = 1.086, 95% CI = 1.083-1.089) when compared with non-rural adult
      residents. Low-SES (OR = 1.976, 95% CI = 1.971-1.982) and middle-SES (OR = 1.596,
      95% CI = 1.592-1.600) adults with current asthma had greater odds of having a
      health service deficit. The percentage of current asthma adults experiencing at
      least one health service deficit by state ranged from a low of 28.5% (Delaware)
      to a high of 58.8% (Wyoming). CONCLUSION: There are clear patterns of disparity
      associated with health services and asthma that can help target interventions.

PMID- 21967576
TI  - Meta-analysis: hyperhomocysteinaemia in inflammatory bowel diseases.
AB  - BACKGROUND: The magnitude of association between homocysteine metabolism and
      inflammatory bowel diseases (IBD) remains unknown, whereas the association
      between hyperhomocysteinaemia and thrombosis remains controversial in IBD. AIM:
      To conduct a systematic review and meta-analysis to examine these issues.
      METHODS: The literature search was conducted using MEDLINE database and
      international conference abstracts from January 1966 to April 2011 and included
      all studies that evaluated plasma homocysteine level in IBD. RESULTS: Twenty
      eight studies evaluated the plasma homocysteine level and/or
      hyperhomocysteinaemia risk in IBD patients. Five studies assessed the association
      of hyperhomocysteinaemia with thrombosis. The mean plasma homocysteine level was
      significantly higher in IBD patients when compared with controls (weighted mean
      difference (WMD)=3.75 MUmol/L; 95% CI, 2.23-5.26 MUmol/L; P<0.0001; reference
      ranges for plasma homocysteine level: 5-12 MUmol/L). The mean plasma homocysteine
      level did not differ between ulcerative colitis (UC) and Crohn's disease (CD)
      (WMD=0.41 MUmol/L; 95% CI, -2.45 to 3.06 MUmol/L; P=0.76). The risk of
      hyperhomocysteinaemia was significantly higher in IBD patients when compared with
      controls [odds ratio (OR)=4.65; 95% CI, 3.04-7.09; P<0.0001]. The risk of
      hyperhomocysteinaemia was not higher among IBD patients who experienced
      thromboembolic complications (OR=1.97; 95% CI, 0.83-4.67; P=0.12). Plasma folate
      level was inversely correlated with IBD risk associated with MTHFR C677T
      polymorphism (P=0.006). CONCLUSIONS: The risk of hyperhomocysteinaemia is
      significantly higher in IBD patients when compared with controls. The risk
      assessment of hyperhomocysteinaemia-related thrombosis in IBD requires further
      investigation. Deficient folate status is associated with a higher impact of
      MTHFR C677T polymorphism on IBD risk.

PMID- 21967577
TI  - Effects of manufactured nanomaterials on fishes: a target organ and body systems
      physiology approach.
AB  - Manufactured nanomaterials (NM) are already used in consumer products and
      exposure modelling predicts releases of ng to low ug l(-1) levels of NMs into
      surface waters. The exposure of aquatic ecosystems, and therefore fishes, to
      manufactured NMs is inevitable. This review uses a physiological approach to
      describe the known effects of NMs on the body systems of fishes and to identify
      the internal target organs, as well as outline aspects of colloid chemistry
      relevant to fish biology. The acute toxicity data, suggest that the lethal
      concentration for many NMs is in the mg l(-1) range, and a number of sublethal
      effects have been reported at concentrations from c. 100 ug to 1 mg l(-1).
      Exposure to NMs in the water column can cause respiratory toxicity involving
      altered ventilation, mucus secretion and gill pathology. This may not lead,
      however, to overt haematological disturbances in the short term. The internal
      target organs include the liver, spleen and haematopoietic system, kidney, gut
      and brain; with toxic effects involving oxidative stress, ionoregulatory
      disturbances and organ pathologies. Some pathology appears to be novel for NMs,
      such as vascular injury in the brain of rainbow trout Oncorhynchus mykiss with
      carbon nanotubes. A lack of analytical methods, however, has prevented the
      reporting of NM concentrations in fish tissues, and the precise uptake mechanisms
      across the gill or gut are yet to be elucidated. The few dietary exposure studies
      conducted show no effects on growth or food intake at 10-100 mg kg(-1) inclusions
      of NMs in the diet of O. mykiss, but there are biochemical disturbances. Early
      life stages are sensitive to NMs with reports of lethal toxicity and
      developmental defects. There are many data gaps, however, including how water
      quality alters physiological responses, effects on immunity and chronic exposure
      data at environmentally relevant concentrations. Overall, the data so far suggest
      that the manufactured NMs are not as toxic as some traditional chemicals (e.g.
      some dissolved metals) and the innovative, responsible, development of
      nanotechnology should continue, with potential benefits for aquaculture,
      fisheries and fish health diagnostics.

PMID- 21967578
TI  - Correlation with larval body size of mRNA levels of growth hormone, growth
      hormone receptor I and insulin-like growth factor I in larval torafugu Takifugu
      rubripes.
AB  - The full-length of insulin-like growth factor (IGF) complementary (c)DNAs encoded
      by igf-I and igf-II from torafugu pufferfish Takifugu rubripes were cloned in the
      present study. The deduced amino acid sequences of the two genes showed c. 80%
      identity each with those of Igf-I and Igf-II from other teleosts, respectively.
      Two growth hormone (GH) receptors, ghr1 and ghr2, were also cloned in silico
      using the T. rubripes Fugu genome database. The transcripts of T. rubripes igf-I
      were detected in slow muscle, heart, skin, gill, liver and intestine but not in
      fast muscle, spleen and testis of adult fish, whereas those of igf-II were found
      in all tissues examined. Subsequently, the accumulated messenger (m)RNA levels of
      igf-I and igf-II were investigated in an F(2)  population derived from a male of
      an apparent fast-growing T. rubripes strain and a wild female T. rubripes
      together with those of other growth-related genes encoding Gh, Ghr1 and Ghr2, and
      with those of prolactin (Prl) and leptin (Lep) previously reported. The
      accumulated mRNA levels of igf-I, gh and ghr1 were significantly correlated to
      growth rate at larval stages in the population, but not for those of igf-II, prl,
      ghr2 and lep. Although it is unclear whether or not this phenotype is directly
      related to the heredity of the fast-growing strain, the findings suggest that the
      expression of igf-I, gh and ghr1 is involved in the regulation of growth rate at
      larval stages in T. rubripes.

PMID- 21967579
TI  - Intergeneric phylogenetic relationships in catfishes of the Loricariinae
      (Siluriformes: Loricariidae), with the description of Fonchiiloricaria nanodon: a
      new genus and species from Peru.
AB  - Recent investigations in the upper Rio Huallaga in Peru revealed the presence of
      an intriguing species of the Loricariinae. To characterize and place this species
      within the evolutionary tree of the subfamily, a molecular phylogeny of this
      group was inferred based on the 12S and 16S mitochondrial genes and the nuclear
      gene F-reticulon4. The phylogeny indicated that this distinctive species was a
      member of the subtribe Loricariina. Given its phylogenetic placement, and its
      unusual morphology, this species is described as a new genus and new species of
      Loricariinae: Fonchiiloricaria nanodon. This new taxon is diagnosed by usually
      possessing one to three premaxillary teeth that are greatly reduced; lips with
      globular papillae on the surface; the distal margin of lower lip bearing short,
      triangular filaments; the premaxilla greatly reduced; the abdomen completely
      covered by plates, with the plates between lateral abdominal plates small and
      rhombic; a caudal fin with 14 rays; the orbital notch absent; five lateral series
      of plates; dorsal-fin spinelet absent; preanal plate present, large and solid,
      and of irregular, polygonal shape, the caudal peduncle becoming more compressed
      posteriorly for the last seven to 10 plates.

PMID- 21967580
TI  - Combined study of daily growth variability and nitrogen-carbon isotopic signature
      analysis of schooling Sardina pilchardus larvae.
AB  - A combined study of Alboran Sea Sardina pilchardus larval daily growth and
      isotopic signature was carried out to elucidate the cause of morphometric
      differences observed in a single larval school whereby the standard length (L(S))
      v. dry mass (M(D)) relationship differentiated a heavier-by-size larval group
      from a lighter larval group. The daily growth analysis revealed that this
      difference originated from two larval growth patterns, where a fast growing
      population (F) in contrast to a slow-growing larval population (S) was
      distinguished. The S-growing larval cohort had a significantly higher nitrogen
      (N) content as a result of greater somatic mass build up with time in the form of
      structural proteins. Alternatively, the F-growing population showed a
      significantly greater amount of carbon (C) content with age, indicating faster
      metabolic rates of C accretion compared to the S-growing group. In consequence,
      the C:N ratios of the F-growing larvae were significantly higher than the S
      group. C:N ratios of both larval populations showed significant linear decrease
      with age (and size), while K showed an inverse relationship. The stable isotopes
      of N did not show significant differences between the S and F-growing larvae. In
      F-growing larvae, however, a significant linear increase in delta(15)N (by age
      class) was observed, indicating that as larvae undergo ontogenetic development,
      trophic level tends to increase. This was also made evident by the significant
      decrease in age of delta(15)N coefficients of variation (by age class). The
      higher delta(13)C values in the S-growing larvae were related to the lower growth
      rates observed in this group. These results suggest a broader trophic flexibility
      in younger larvae, but moving towards a trophic specialization and more selective
      diets with age. This trophic specialization shows a tendency of a greater prey
      size with age. These findings suggest that S-growing larvae have a more
      omnivorous diet than the F-growing ones.

PMID- 21967581
TI  - Reproductive aspects of the yellowtail snapper Ocyurus chrysurus from the
      southern Gulf of Mexico.
AB  - In this study, sex ratio, spawning season, fork length (L(F)) at maturity
      (L(F50)), batch fecundity and spawning frequency were characterized for the
      continental population of Ocyurus chrysurus from the Campeche Bank, in the
      southern Gulf of Mexico. A total of 1657 specimens were collected from February
      2008 to January 2009. The overall sex ratio (male:female) and sex ratios by size
      class showed no significant differences from an expected 1:1 ratio. The Campeche
      Bank population did not conform to the reproductive seasonality pattern
      characteristic of a continental population. A protracted spawning season that
      extended from January to September with peaks occurring mainly between April and
      May and additionally in September was observed. The population conformed,
      however, to the sexual maturity pattern observed for populations and species
      associated with a continental margin. Fish of both sexes reached the onset of
      sexual maturity at a similar and small L(F) of c. 14 cm, and L(F50) (L(F) at
      which 50% of females and males become mature) was 21.3 and 19.4 cm. Asynchronous
      type ovarian development was observed for this species and batch fecundity
      estimates ranged from 14,102 to 164,756 oocytes (mean +/-S.D. = 43,852 +/- 32,684
      oocytes). The overall spawning frequency estimate was once every 8.3 days or 26
      times during the 9 month spawning season.

PMID- 21967582
TI  - Environmental factors influencing adult sex ratio in Poecilia reticulata:
      laboratory experiments.
AB  - The potential causes of adult sex ratio variation in guppies Poecilia reticulata
      were tested in laboratory experiments that evaluated the mortality rates of male
      and female P. reticulata exposed to potential predators (Hart's rivulus Rivulus
      hartii and freshwater prawns Macrobrachium crenulatum) and to different resource
      levels. Poecilia reticulata mortality increased in the presence of R. hartii and
      M. crenulatum, and low resource levels had an effect on mortality only in the
      presence of M. crenulatum. Rivulus hartii preyed more often on male than on
      female P. reticulata, and this sex-biased predation was not simply the result of
      males being smaller than females. In contrast, no sex-biased mortality was
      attributable to M. crenulatum or low resource levels.

PMID- 21967583
TI  - Squalus formosus, a new species of spurdog shark (Squaliformes: Squalidae), from
      the western North Pacific Ocean.
AB  - A new species of spurdog, Squalus formosus n. sp., from the lower continental
      shelf and upper continental slope off the coast of Taiwan and southern Japan, is
      described. It belongs to the 'highfin megalops group', the members of which share
      a short snout, high dorsal fins, robust dorsal spines, tricuspid denticles and a
      white posterior caudal margin. Squalus formosus is most similar to Squalus
      albifrons, a recently described species from eastern Australia, but differs in
      some morphological characters and fin colouration. Squalus formosus is sympatric
      with three other species of Squalus in Taiwanese waters, i.e. Squalus
      brevirostris, Squalus japonicus and Squalus mitsukurii, and can be readily
      distinguished from these in the following combination of characters: tall and
      upright first dorsal fin, with a tall and robust spine, short and bluntly pointed
      snout, white caudal-fin posterior margin and first dorsal fin with a white
      anterior margin parallel with dorsal spine. This new species was considered by
      some authors to be conspecific with Squalus blainville from the eastern Atlantic
      Ocean, but the results of this study reveal that it is probably endemic to Taiwan
      and southern Japan.

PMID- 21967584
TI  - Behaviour of rainbow trout Oncorhynchus mykiss presented with a choice of
      normoxia and stepwise progressive hypoxia.
AB  - The objective of this study was to identify behavioural adjustments leading to
      avoidance of hypoxia. Using the oxygen-sensitive species rainbow trout
      Oncorhynchus mykiss as a model, individual fish were recorded while moving freely
      between two sides of a test arena: one with normoxia and one with stepwise
      progressive hypoxia [80-30% dissolved oxygen (DO) air saturation]. The results
      demonstrated a gradual decrease in the total time spent in hypoxia starting at
      80% DO air saturation. At this DO level, the avoidance of hypoxia could not be
      attributed to changes in spontaneous swimming speed, neither in normoxia nor in
      hypoxia. Reducing the DO level to 60% air saturation resulted in decreased
      spontaneous swimming speed in normoxia, yet the number of trips to the hypoxic
      side of the test arena remained unchanged. Moreover, data revealed increased
      average residence time per trip in normoxia at DO levels <=60% air saturation and
      decreased average residence time per trip in hypoxia at DO levels <=50% air
      saturation. Finally, the spontaneous swimming speed in hypoxia increased at DO
      levels <=40% air saturation and the number of trips to hypoxia decreased at the
      30% DO air saturation level. Thus, avoidance of the deepest hypoxia was connected
      with a reduced number of trips to hypoxia as well as decreased and increased
      spontaneous swimming speed in normoxia and hypoxia, respectively. Collectively,
      the data support the conclusions that the mechanistic basis for avoidance of
      hypoxia may (1) not involve changes in swimming speed during mild hypoxia and (2)
      depend on the severity of hypoxia.

PMID- 21967585
TI  - Extended incubation affects larval morphology, hatching success and starvation
      resistance in a terrestrially spawning fish, Galaxias maculatus (Jenyns 1842).
AB  - The effect of extended incubation (delayed hatching) on larval morphology in the
      terrestrially spawning common galaxias Galaxias maculatus was investigated by
      inducing larvae to hatch 1 and 2 weeks after the normal 2 week incubation period.
      After 1 week of extended incubation, larvae were larger (longer in standard
      length, L(S), and greater in body depth) compared to controls (larvae that
      experienced normal incubation durations). After 2 weeks of extended incubation,
      larvae were smaller (shorter in L(S) and smaller in body depth) than larvae that
      experienced 1 week of extended incubation. Furthermore, eye area increased while
      yolk-sac size decreased monotonically with increasing incubation duration. These
      results suggest that larvae experiencing long periods of extended incubation are
      using somatic tissue to meet their metabolic demands. Larvae that experienced 2
      weeks of extended incubation succumbed to starvation sooner than control larvae,
      but hatching success was not significantly different. Temperature mediated the
      effect of extended incubation on the morphology of larvae at hatching, most
      likely, through its effects on developmental rate and efficiency of yolk
      utilization. This study demonstrates some of the consequences of terrestrial
      spawning with extended incubation, which will assist in determining why this
      intriguing behaviour has evolved several times in a diverse range of taxa.

PMID- 21967586
TI  - Normal axial skeleton structure in common roach Rutilus rutilus (Actinopterygii:
      Cyprinidae) and malformations due to radiation contamination in the area of the
      Mayak (Chelyabinsk Province, Russia) nuclear plant.
AB  - This study was designed to describe normal axial skeletal structure in common
      roach Rutilus rutilus from putative unaffected environmental conditions, and the
      occurrence of skeletal malformations in the fish from an area under radiation
      contamination. Specimens were collected from water bodies of the Techa Cascade
      Reservoirs located near the Mayak atomic industry plant in the River Ob'
      drainage, Chelyabinsk Province, Russia. One sample was collected from Lake
      Irtyash, a reservoir of drinkable water, supplying the town of Ozersk, and the
      other one from a technical reservoir which is a storage of liquid radioactive
      waste from Mayak and characterized by high radioactive contamination (mostly
      (90)Sr and (137)Cs). A comparison was made with historical material collected
      from the River Ob' before the middle of the 20th century, i.e. before the
      environment became affected by radioactive contamination. A high number of
      abnormalities of the axial skeleton were detected in both Mayak samples, in 94
      and 97% of examined specimens, in contrast to about 20% in the historical
      specimens. The abnormalities were in both the unpaired fins and the vertebral
      column, including the caudal complex and included supernumerary elements,
      fusions, deformities and displacement of the elements. Most axial skeleton
      abnormalities, however, were minor, such as splitting, shortening or deformation
      of spines. Severe defects, such as extensive scolioses, lordoses and kyphoses,
      were not found. The causes of the abnormalities were not identified in this
      study, but the high incidence of malformations may be attributed to genetically
      determined imbalance during development. The almost equal distribution of
      abnormalities among the fish from non-contaminated and radioactive contaminated
      reservoirs may be explained by either recent gene flow within the population of
      R. rutilus in the River Techa system or the effect of unknown unfavourable
      environmental factors such as chemical pollution.

PMID- 21967587
TI  - The influence of selection for vulnerability to angling on foraging ecology in
      largemouth bass Micropterus salmoides.
AB  - Several traits related to foraging behaviour were assessed in young-of-the-year
      produced from largemouth bass Micropterus salmoides that had been exposed to four
      generations of artificial selection for vulnerability to angling. As recreational
      angling may target foraging ability, this study tested the hypothesis that
      selection for vulnerability to angling would affect behaviours associated with
      foraging ecology and prey capture success. Fish selected for low vulnerability to
      angling captured more prey and attempted more captures than high vulnerability
      fish. The higher capture attempts, however, ultimately resulted in a lower
      capture success for low vulnerability fish. Low vulnerability fish also had
      higher prey rejection rates, marginally shorter reactive distance and were more
      efficient at converting prey consumed into growth than their high vulnerability
      counterparts. Selection due to recreational fishing has the potential to affect
      many aspects of the foraging ecology of the targeted population and highlights
      the importance of understanding evolutionary effects and how these need to be
      considered when managing populations.

PMID- 21967588
TI  - Morphological and reproductive variation among populations of the Pacific molly
      Poecilia butleri.
AB  - In viviparous organisms, pregnant females typically experience an increase in
      body mass and body volume. In this study, the prediction that variation in
      reproductive traits among populations of viviparous organisms should be related
      to variation among populations in body shape was tested in the Pacific molly
      Poecilia butleri, a viviparous fish that inhabits western Mexico and northern
      Central America. Variation among 10 populations in four reproductive traits was
      examined: brood size, individual embryo mass, total reproductive allotment and
      degree of maternal provisioning of nutrients to developing embryos. Variation
      among these populations in body shape was also examined. Significant variation
      among populations was observed in both brood size and reproductive allotment but
      not in embryo mass or degree of maternal provisioning. Significant variation
      among populations was also observed in body shape. After correcting for female
      size, however, reproductive traits and body shape were not associated among
      populations. This suggests that selective pressures acting on reproduction do not
      necessarily affect morphology and vice versa. Several factors might contribute to
      this unexpected lack of association between reproductive traits and morphology.

PMID- 21967589
TI  - Evidence for multiple historical colonizations of an endoreic drainage basin by
      an Australian freshwater fish.
AB  - The contemporary and historical colonization capacity of an Australian freshwater
      fish, north-west glassfish Ambassis sp., was tested using mtDNA sequence data and
      six newly developed microsatellite loci in an endoreic basin in central
      Australia. Overall, Ambassis sp. exhibited weak genetic structure within
      catchments, suggesting some capacity to recolonize extirpated waterholes after
      disturbance. Genetic structure revealed that the historical pattern of
      connectivity among catchments in the Lake Eyre Basin was dramatically different
      from other species studied in this region. Two highly divergent clades were
      detected in separate catchments in the basin. mtDNA from individuals sampled in
      catchments north of the Lake Eyre Basin suggest that Ambassis sp. has colonized
      on two separate occasions from catchments in northern Australia, subsequently
      generating two highly divergent lineages.

PMID- 21967590
TI  - Surgical wound healing in radio-tagged adult Pacific lamprey Entosphenus
      tridentatus held on different substrata.
AB  - Radio-tagged adult Pacific lamprey Entosphenus tridentatus held in a raceway with
      Plexiglas-lined walls and bottom healed more slowly and retained sutures longer
      than fish held in an all-concrete raceway or one with Plexiglas walls and a
      cobble-lined bottom. On all substrata, healing depended on when sutures were
      lost, and fish that lost their sutures in <14 days post-surgery healed faster
      than those that kept sutures longer. Long-term suture retention led to tissue
      trauma, infection and poor survival.

PMID- 21967591
TI  - Is the adipose fin and the lower jaw (kype) related to social dominance in male
      Arctic charr Salvelinus alpinus?
AB  - This study reports on the importance of the size of the kype (lower jaw) and the
      adipose fin for establishing and maintaining social dominance in pair-wise
      interactions among size-matched, reproductively active male Arctic charr
      Salvelinus alpinus. The size of these traits seems not to have a large influence
      on establishing dominance, but after 4 days of social interactions, and after
      dominance rank is established, subordinate males show reduced size of their
      adipose fins and kypes relative to that of dominant males. Consequently, these
      traits seem to be costly labile characters that could be of importance in inter
      and intra-sexual evaluations of individual quality.

PMID- 21967594
TI  - Irritant contact dermatitis: effect of age.
AB  - Knowledge on age-relationship to irritant contact dermatitis (ICD) remains of
      interest. We searched for articles and textbooks on age-relationship to ICD and
      evaluated relevant data. Irritant response may be enhanced in children and
      decline with increasing age. In general, older skin reacts more slowly and with
      less intensity to irritants when compared with young skin. Such age-related
      changes may depend: (i) on differences in percutaneous penetration in old and
      young skin, and/or on (ii) differences in the microcirculatory efficiency, which
      serves as the route by which inflammatory cells make their way to the site of
      inflammation. Additionally, stratum corneum turnover time increases with age
      which means that an irritant remains longer on the skin; a compromised cutaneous
      blood vessel network with ageing may lead to a decreased inflammatory response,
      decreased absorption and decreased clearance. In conclusion, age-related
      differences of ICD are present despite some conflicting data. Investigations
      elucidating this interesting subject may benefit in prevention and intervention
      strategies.

PMID- 21967596
TI  - Adolescents with implantable cardioverter defibrillators: a patient and parent
      perspective.
AB  - BACKGROUND: An implantable cardioverter defibrillator (ICD) is a device used in
      the treatment of individuals with life-threatening cardiac conditions. These
      include genetic disorders such as long QT syndrome, hypertrophic cardiomyopathy,
      and Brugada syndrome, all of which have the propensity to cause sudden cardiac
      death. Adults with ICDs consistently report elevated levels of anxiety and
      depression, as well as negative lifestyle changes associated with the device.
      Compared to older ICD recipients, young patients face decades of life with the
      device and the long-term impact and implications are important to consider. This
      research explores the experiences of adolescents living with an ICD. Parents of
      these adolescents were also included to explore the impact on them as the primary
      caregivers. METHODS: A qualitative approach was chosen to explore the lived
      experience; semistructured interviews with six adolescents and six parents were
      conducted from which a number of key themes emerged. RESULTS: The experiences
      described by participants included the restrictions adolescents face, the ICD
      shock experience, and ongoing challenges post-ICD implantation. However, both
      adolescents and parents were able to adjust to life after receiving an ICD and
      described several benefits associated with having the device. Findings also
      emerged relating to communication between health professionals and adolescents,
      and the limitations adolescents impose on themselves post-ICD implantation.
      CONCLUSION: These findings have important implications for clinical practice and
      may help guide medical management for adolescents with ICDs and their families.

PMID- 21967597
TI  - Investigations on ferroelectric liquid crystal by high resolution TEM and solid
      state 13C NMR.
AB  - In order to investigate the structural and dynamical properties of ferroelectric
      liquid crystal (FLC) in different phases a model compound [4-(3)-(S)-methyl-2-(S)
      chloropentanoyloxy)]-4'-nonyloxy-biphenyl (3M2CPNOB) is synthesized. High
      resolution transmission electron microscopy (HR-TEM) is applied to observe the
      morphology of 3M2CPNOB and temperature-dependent solid state (13)C NMR to record
      (13)C chemical shifts at different phases. A liquid nitrogen quenching method is
      used to maintain the conformation of the mesophases for HR-TEM experiments. TEM
      images show that all the smectic A (SmA), smectic C* (SmC*) and crystalline
      phases have lamellar morphology. The interplanar distances in the crystalline
      phase are smaller than those in SmA and SmC* phases because of denser arrangement
      of the molecules. Both (13)C chemical shifts and line shape vary with different
      phases. The experimental results suggest that SmC* phase as an intermediate
      occurs in the anisotropy transition process from SmA to crystalline phase, the
      helical structure of the SmC* phase unwinds in the magnetic field and the
      conformations of the SmA and isotropic phase are very similar.

PMID- 21967595
TI  - Supported membranes embedded with fixed arrays of gold nanoparticles.
AB  - We present a supported membrane platform consisting of a fluid lipid bilayer
      membrane embedded with a fixed array of gold nanoparticles. The system is
      realized by preforming a hexagonal array of gold nanoparticles (~5-7 nm) with
      controlled spacing (~50-150 nm) fixed to a silica or glass substrate by block
      copolymer lithography. Subsequently, a supported membrane is assembled over the
      intervening bare substrate. Proteins or other ligands can be associated with the
      fluid lipid component, the fixed nanoparticle component, or both, providing a
      hybrid interface consisting of mobile and immobile components with controlled
      geometry. We test different biochemical coupling strategies to bind individual
      proteins to the particles surrounded by a fluid lipid membrane. The coupling
      efficiency to nanoparticles and the influence of nanoparticle arrays on the
      surrounding membrane integrity are characterized by fluorescence imaging,
      correlation spectroscopy, and super-resolution fluorescence microscopy. Finally,
      the functionality of this system for live cell experiments is tested using the
      ephrin-A1-EphA2 juxtacrine signaling interaction in human breast epithelial
      cells.

PMID- 21967598
TI  - Reply to: 'Primary focal hyperhidrosis: current treatment options and a step-by
      step approach'.

PMID- 21967599
TI  - QTAIM analysis of the HF, HCl, HBr, and HOH elimination reactions of
      halohydrocarbons and halohydroalcohols.
AB  - The 1,2-HX elimination reaction (where X = F, Cl, Br, OH) has been established as
      an important reaction in the degradation of compounds introduced into the upper
      atmosphere, including common CFC replacement compounds. By analyzing the electron
      densities of the transition state geometries of these reactions using QTAIM, we
      see that we can divide these reactions into two types. For HF and HOH
      elimination, the transition state is a complete ring of bonds, and neither the C
      H nor the C-X bonds have been broken at the maximum of energy. There is very
      little accumulation of electron density on the X atom, with the majority of
      charge being lost by the hydrogen atom undergoing elimination, being transferred
      on to the two carbon atoms. In HCl and HBr elimination, a similar loss of
      electron density of the hydrogen atom is accompanied by significant accumulation
      of electron density on the X atom and a smaller change in electron density on the
      carbon atoms. The C-X bond is broken in the transition state geometry, with no
      ring critical point being present. This may explain the relative stabilities of
      halohydrocarbons and haloalcohols with respect to loss of H-X.

PMID- 21967600
TI  - Rugby athletes' awareness and compliance in the use of mouthguards in the North
      West of Italy.
AB  - BACKGROUND: The prevention of dental injuries during full-contact sports such as
      rugby is extremely important. Wearing a mouthguard can significantly reduce the
      frequency and severity of orofacial injuries, but it is not always used as
      athletes find it difficult to tolerate. The purpose of the present study was to
      determine the awareness and the extent of mouthguard use in a sample of young
      rugby athletes in the North West of Italy. MATERIAL AND METHODS: The athletes of
      four amateurs rugby teams based in the Province of Turin, Italy completed a
      questionnaire about playing history, current use and type of mouthguards,
      disturbs associated with mouthguard use, and general attitudes towards
      mouthguards. RESULTS: Only 53.85% of the subjects reported wearing their
      mouthguard all the time both during training and games. The most commonly
      reported problem associated with using a mouthguard was the discomfort on speech,
      followed by difficulty in closing lips, adversely affected breathing, adversely
      affected swallowing and slipping sensation. A statistically significant
      association between patients <22 years and non-use of mouthguards was observed.
      CONCLUSION:  Limited knowledge about oral injury prevention and limited use of
      mouthguards were observed. The present study suggests that educational courses
      for rugby players and coaches to promote the use of mouthguards would be
      extremely important to reduce common complaints about these devices and increase
      their usage.

PMID- 21967601
TI  - Developmental and disease-related influences on self-management acquisition among
      pediatric liver transplant recipients.
AB  - Pediatric LT recipients are vulnerable to disruptions in their healthcare
      management and transitioning to self-managed care. This study aimed to examine
      whether age at transplant and indication for transplant (acute vs. chronic liver
      disease) influence later self-management skills. Sixty-three LT recipients, aged
      14 and older (M = 17.68, s.d. = 3.01), were recruited and asked to complete a
      healthcare management survey, the Developmentally Based Skills Checklist, adapted
      for transplant patients, listing 22 behaviors that medically ill adolescents
      should progressively master. While there were no significant differences between
      those who received an LT owing to an acute disease vs. those who received an LT
      owing to a chronic disease, the age at which patients received their transplant
      did yield significant results, although, overall, these findings were attenuated
      by current age. However, our findings indicated that males transplanted at a
      younger age struggled with mastery over their healthcare responsibilities
      relative to males transplanted later and females in both age groups. There are
      many possible reasons why the experience of transplant at a younger age could
      negatively affect or derail healthcare transitions. Future research is necessary
      to further untangle this relationship; yet, it seems as though longer time living
      with LT may make transition harder for families.

PMID- 21967602
TI  - Malakoplakia.
AB  - Malakoplakia is a rare, chronic disease with pleomorphic presentation. It occurs
      most frequently in immunocompromised patients. It is believed that this entity
      represents an unusual response to bacterial infection in which macrophages fail
      to phagocytose them properly. It involves many organs, particularly the urinary
      and gastrointestinal tracts. It is uncommon on the skin and less common in
      children. The diagnosis is usually based on histopathologic findings.

PMID- 21967603
TI  - Facial memory deficits in children with fetal alcohol spectrum disorders.
AB  - Prenatal exposure to alcohol may lead to a range of neurobehavioral effects,
      including impaired learning and memory. Although children with fetal alcohol
      spectrum disorders (FASD) exhibit both verbal and nonverbal memory impairments,
      their memory for faces has not been as thoroughly investigated and the extent
      literature provides inconsistent results. The aim of the current study was to
      determine whether difficulties in face memory exist in children with FASD and
      whether the difficulties are mediated by task demands. To address this, we used
      two measures of immediate and delayed facial recognition memory, the Children's
      Memory Scale (CMS) and Test of Memory and Learning (TOMAL). Compared to typically
      developing controls, children with FASD showed memory deficits on all tests and
      were more likely to perform in a clinically significant range. As well, children
      performed more poorly on the CMS compared to TOMAL, a finding consistent with the
      greater difficulty of the CMS task. Our results are consistent with our
      hypothesis that children with FASD show impairment in facial memory, particularly
      on demanding memory tasks.

PMID- 21967604
TI  - A 6-month analysis of training-intensity distribution and physiological
      adaptation in Ironman triathletes.
AB  - In the present study, we analysed the training-intensity distribution and
      physiological adaptations over a 6-month period preceding an Ironman triathlon
      race. Ten athletes (mean +/- s: age 43 +/- 3 years, mass 78.3 +/- 10.3 kg,
      stature 1.79 +/- 0.05 m) participated in the study. The study consisted of three
      training periods (A, B, C), each of approximately 2 months' duration, and four
      testing weeks. Testing consisted of incremental tests to exhaustion for swimming,
      cycling and running, and assessments for anthropometry plus cardiovascular and
      pulmonary measures. The lactate threshold and the lactate turnpoint were used to
      demarcate three discipline-specific, exercise-intensity zones. The mean
      percentage of time spent in zones 1, 2, and 3 was 69 +/- 9%, 25 +/- 8%, and 6 +/-
      2% for periods A-C combined. Only modest physiological adaptation occurred
      throughout the 6-month period, with small to moderate effect sizes at best.
      Relationships between the training volume/training load and the training
      intensity distribution with the changes in key measures of adaptation were weak
      and probably reflect differences in initial training status. Our results suggest
      that the effects of intensity distribution are small over short-term training
      periods and future experimental research is needed to clarify the potential
      impact of intensity distribution on physiological adaptation.

PMID- 21967605
TI  - 4-Hydroxy-2(E)-nonenal metabolism differs in Apc(+/+) cells and in Apc(Min/+)
      cells: it may explain colon cancer promotion by heme iron.
AB  - Animal and epidemiological studies suggest that dietary heme iron would promote
      colorectal cancer. Oxidative properties of heme could lead to the formation of
      cytotoxic and genotoxic secondary lipid oxidation products, such as 4-hydroxy
      2(E)-nonenal (HNE). This compound is more cytotoxic to mouse wild-type colon
      cells than to isogenic cells with a mutation on the adenomatous polyposis coli
      (APC) gene. The latter thus have a selective advantage, possibly leading to
      cancer promotion. This mutation is an early and frequent event in human
      colorectal cancer. To explain this difference, the HNE biotransformation
      capacities of the two cell types have been studied using radiolabeled and stable
      isotope-labeled HNE. Apc-mutated cells showed better biotransformation capacities
      than nonmutated cells did. Thiol compound conjugation capacities were higher for
      mutated cells, with an important advantage for the extracellular conjugation to
      cysteine. Both cells types were able to reduce HNE to 4-hydroxynonanal, a
      biotransformation pathway that has not been reported for other intestinal cells.
      Mutated cells showed higher capacities to oxidize 4-hydroxynonanal into 4
      hydroxynonanoic acid. The mRNA expression of different enzymes involved in HNE
      metabolism such as aldehyde dehydrogenase 1A1, 2 and 3A1, glutathione transferase
      A4-4, or cystine transporter xCT was upregulated in mutated cells compared with
      wild-type cells. In conclusion, this study suggests that Apc-mutated cells are
      more efficient than wild-type cells in metabolizing HNE into thiol conjugates and
      4-hydroxynonanoic acid due to the higher expression of key biotransformation
      enzymes. These differential biotransformation capacities would explain the
      differences of susceptibility between normal and Apc-mutated cells regarding
      secondary lipid oxidation products.

PMID- 21967606
TI  - Role of corticotropin-releasing factor in the median raphe nucleus in yohimbine
      induced reinstatement of alcohol seeking in rats.
AB  - The pharmacological stressor yohimbine increases ongoing alcohol self
      administration and reinstates alcohol seeking in rats. This effect is attenuated
      by systemic injections of a corticotropin-releasing factor (CRF) antagonist. The
      brain sites involved in CRF's role in yohimbine-induced alcohol taking and
      seeking are unknown. We report that injections of the CRF receptor antagonist d
      Phe CRF into the median raphe nucleus (MRN) attenuated yohimbine-induced
      reinstatement of alcohol seeking but had no effect on yohimbine-induced increases
      in alcohol intake during ongoing self-administration. Results indicate an
      important role of MRN CRF receptors in yohimbine-induced reinstatement of alcohol
      seeking but not yohimbine-induced increases in alcohol intake.

PMID- 21967607
TI  - Clinical and genetic analyses of three Korean families with hereditary
      hemorrhagic telangiectasia.
AB  - BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant
      vascular disorder, characterized by recurrent epistaxis, mucocutaneous
      telangiectases, and arteriovenous malformations (AVMs) in various visceral
      organs. Endoglin (ENG) and activin receptor-like kinase 1 (ACVRL1; ALK1),
      receptors for transforming growth factor-beta (TGF-beta) superfamily, have been
      identified as the principal HHT-causing genes. METHODS: Three unrelated Korean
      HHT patients and their asymptomatic as well as symptomatic family members were
      genetically diagnosed by sequencing whole exons and their flanking regions of ENG
      and ACVRL1. Functionality of an aberrant translation start codon, which is
      created by a substitution mutation at the 5'-untranslated region (UTR) of ENG
      found in a HHT family, was tested by transient in vitro transfection assay. Decay
      of the mutant transcripts was also assessed by allele-specific expression
      analysis. RESULTS: Two ENG and one ACVRL1 mutations were identified: a known ENG
      mutation (c.360+1G > A; p.Gly74_Tyr120del); a novel ENG mutation (c.1-127C > T);
      and a novel ACVRL1 mutation (c.252_253insC; p.Val85fsX168). We further validated
      that the 5'-UTR ENG mutation prevents translation of ENG from the biological
      translation initiation site of the mutant allele, and leads to degradation of the
      mutant transcripts. CONCLUSIONS: This is the first experimental demonstration
      that a 5'-UTR mutation can prevent translation of ENG among HHT patients, and
      further supports the previous notion that haploinsufficiency is the primary
      mechanism of HHT1. Our data also underscore the importance of including exons
      encoding 5' UTR for HHT mutation screening.

PMID- 21967608
TI  - Prepared for the best: readiness to modify attentional processing and reduction
      in anxiety vulnerability in response to therapy.
AB  - Individuals differ in the extent to which their vulnerability to anxiety is
      reduced by psychological therapy. However, the cognitive basis for such
      individual differences is still poorly understood. To test a cognitive account of
      differences in anxiety reduction in response to treatment, the present study
      examined individuals undergoing group therapy for social anxiety disorder. We
      assessed whether differences in their readiness to adopt selective attentional
      processing in response to an experimental contingency predicted positive changes
      in a range of anxiety measures in response to treatment. Findings were consistent
      with the position that readiness to alter attentional processing bias may
      underpin individual differences in the tendency to respond to positive
      experiential conditions, such as group therapy, by reducing anxiety
      vulnerability.

PMID- 21967609
TI  - Low-dose rituximab is effective in pemphigus.
AB  - BACKGROUND: Rituximab, an anti-CD20 antibody, was shown in open series studies to
      be effective in treating pemphigus at a dose of 4 * 375 mgm(-2) as approved for B
      cell malignancies. OBJECTIVES: We investigated whether a lower dose of rituximab
      is also effective for pemphigus. METHODS: Patients with pemphigus were treated
      with a single course of two infusions of rituximab (500 mg each) at an interval
      of 2 weeks. Clinical consensus late end points, B-cell number, desmoglein 1 and
      desmoglein 3 indices were monitored. RESULTS: We enrolled 15 patients in the
      study: three with pemphigus foliaceus (PF) and 12 with pemphigus vulgaris (PV).
      The follow-up was 32-152 weeks (median 94). All 15 patients responded to therapy.
      Eight patients achieved complete remission in a median period of 5 weeks (four on
      minimal therapy, four off therapy). Seven patients achieved partial remission in
      a median period of 34.5 weeks (five on minimal therapy, two off therapy).
      Relapses (40%) were seen between 53 and 103 weeks (median 97) after start of
      therapy. B-cell numbers dropped to <1% after first infusion, and remained
      undetectable in patients with sustained remission. The antidesmoglein 1 index
      correlated well with the clinical severity in PF, but this was less obvious in
      PV. CONCLUSIONS: A low dose of rituximab is an effective and safe treatment for
      pemphigus. Relapses may occur, mostly at the end of the second year. Cost
      effectiveness studies with a long follow-up are required to determine the proper
      dosage of this expensive drug in pemphigus.

PMID- 21967610
TI  - Plant polyphenols regulate chemokine expression and tissue repair in human
      keratinocytes through interaction with cytoplasmic and nuclear components of
      epidermal growth factor receptor system.
AB  - AIMS: To evaluate mechanisms underlying modulation of inflammatory chemokines in
      primary human keratinocytes (normal human epidermal keratinocytes) and repair
      related processes in wound models by plant polyphenols (PPs) with antioxidant and
      superoxide scavenging properties (verbascoside [Vb], resveratrol [Rv], polydatin
      [Pd], quercetin [Qr], and rutin). RESULTS: Epidermal growth factor receptor
      (EGFR)-controlled chemokines CXCL8/interleukin 8 (IL-8), CCL2/monocyte
      chemotactic protein-1 (MCP-1), and CXCL10/interferon gamma-produced protein of 10
      kDa (IP-10) were modulated by transforming growth factor alpha (TGF-alpha) and by
      the tumor necrosis factor alpha/interferon gamma combination (T/I). EGFR
      phosphorylation, nuclear translocation, and downstream cytoplasmic signaling
      pathways (extracellular regulation kinase [ERK]1/2, p38, STAT3, and PI-3K) were
      studied. All PPs did not affect TGF-alpha-induced STAT3 phosphorylation, whereas
      they suppressed T/I-activated NFkappaB and constitutive and T/I-induced but not
      TGF-alpha-induced ERK1/2 phosphorylation. Vb and Qr suppressed total EGFR
      phosphorylation, but they synergized with TGF-alpha to enhance nuclear
      accumulation of phosphorylated EGFR. Vb strongly inhibited TGF-alpha-induced p38
      phosphorylation and T/I-induced NFkappaB and activator protein-1 (AP-1) binding
      to DNA. Vb was an effective inhibitor of T/I-stimulated chemokine synthesis, and
      it accelerated scratch wound healing in vitro. Anti-inflammatory and wound
      healing activities of Vb were confirmed in vivo in the full-thickness excision
      wound. Although Pd and Rv did not affect EGFR activation/translocation, they and
      Qr synergized with TGF-alpha and T/I in the induction of IL-8
      transcription/synthesis while opposing enhanced MCP-1 and IP-10
      transcription/synthesis connected with pharmacologically impaired EGFR
      functioning. INNOVATION: PPs perturb the EGFR system in human keratinocytes, and
      this effect may be implicated in the regulation of inflammatory and repair
      related processes in the skin. CONCLUSION: Anti-inflammatory and wound healing
      effects of PPs depend on their interaction with EGFR-controlled cytoplasmic and
      nuclear pathways rather than on their direct redox properties.

PMID- 21967611
TI  - Genetic modifiers of sickle cell disease.
AB  - Sickle cell disease is one of the best characterized human monogenic disorders.
      Complex genotype/phenotype correlations clearly demonstrate the interaction of
      multiple genetic and environmental factors. In the last 20 years, scientific
      research has applied genetic approaches to dissect some of these modifiers. This
      review highlights the more recent genetic association studies that have been
      applied to unravel the genetic modifiers of sickle cell disease including Hb F
      genetics, and the key genetic variants identified. Illumination of such modifying
      factors may guide future therapeutic interventions and improve prediction of
      disease severity, with implications for genetic counseling, prenatal diagnosis
      and implementation of high risk therapy.

PMID- 21967612
TI  - Metallothioneins protect cytosolic creatine kinases against stress induced by
      nitrogen-based oxidants.
AB  - The formation of intracellular nitrogen-based oxidants has important
      physiological and pathological consequences. CK (creatine kinase), which plays a
      key role in intracellular energy metabolism, is a main target of low
      concentrations of oxidative and nitrative stresses. In the present study, the
      interaction between cytosolic CKs [MM-CK (muscle-type CK) and BB-CK (brain-type
      CK)] and MTs [metallothioneins; hMT2A (human MT-IIA) and hMT3 (human MT-III)]
      were characterized by both in vitro and intact-cell assays. MTs could
      successfully protect the cytosolic CKs against inactivation induced by low
      concentrations of PN (peroxynitrite) and NO both in vitro and in hMT2A
      overexpressing H9c2 cells and hMT3-knockdown U-87 MG cells. Under high PN
      concentrations, CK formed granule-like structures, and MTs were well co-localized
      in these aggregated granules. Further analysis indicated that the number of cells
      containing the CK aggregates negatively correlated with the expression levels of
      MTs. In vitro experiments indicated that MTs could effectively protect CKs
      against aggregation during refolding, suggesting that MT might function as a
      chaperone to assist CK re-activation. The findings of the present study provide
      direct evidence of the connection between the two well-characterized
      intracellular systems: the precisely balanced energy homoeostasis by CKs and the
      oxidative-stress response system using MTs.

PMID- 21967613
TI  - Congenitally corrected transposition of the great arteries with severely stenotic
      bicuspid aortic valve in an adult: a case report.
AB  - Congenitally corrected transposition of the great arteries (CCTGA) is a rare
      disease accounting for 0.5-1.4% of patients with congenital heart disease. In
      this congenital cardiopathy, the left atrium is connected to the right ventricle,
      from which the aorta stems. We present a case of an adult with CCTGA associated
      with aortic stenosis and bicuspid aortic valve-an association not yet described
      to our knowledge. 

PMID- 21967614
TI  - Stepping towards prevention of bone loss after stroke: a systematic review of the
      skeletal effects of physical activity after stroke.
AB  - Bone loss after stroke is pronounced, and contributes to increased fracture risk.
      People who fracture after stroke experience reduced mobility and increased
      mortality. Physical activity can maintain or improve bone mineral density and
      structure in healthy older adults, likely reducing fracture risk. The purpose of
      this systematic review was to investigate the skeletal effects of physical
      activity in adults affected by stroke. A search of electronic databases was
      undertaken. Selection criteria of trials were * prospective and controlled *
      physical activity-based intervention * participants with history of stroke, and *
      bone-related outcome measures. Effect sizes were calculated for outcomes of
      paretic and nonparetic limbs. Three of 349 identified records met the inclusion
      criteria. Small effect sizes were found in favor of physical activity in adults
      with chronic stroke (n=95, 40% female, average age 63.8 years, more than one-year
      poststroke). Patients in intervention groups had significantly higher changes in
      femoral neck bone mineral density, tibial cortical thickness and trabecular bone
      mineral content of the paretic limb, compared with controls (P<0.05). It is not
      known whether these benefits reduced fracture risk. There are limited studies
      investigating the skeletal effect of physical activity for adults poststroke.
      Given the increased risk of, and poor outcomes following a fracture after stroke,
      randomized trials are warranted to investigate the benefits of physical activity
      on bone, after stroke. Interventions are likely to be beneficial if implemented
      soon after stroke, when bone loss appears to be rapid and pronounced.

PMID- 21967615
TI  - Reversible cross-linking of polyisoprene coronas in micelles, block comicelles,
      and hierarchical micelle architectures using Pt(0)-olefin coordination.
AB  - Previous work has established that polyisoprene (PI) coronas in cylindrical block
      copolymer micelles with a poly(ferrocenyldimethylsilane) (PFS) core can be
      irreversibly cross-linked by hydrosilylation using (HSiMe(2))(2)O in the presence
      of Karstedt's catalyst. We now show that treatment of cylindrical PI-b-PFS
      micelles with Karstedt's catalyst alone, in the absence of any silanes, leads to
      PI coronal cross-linking through Pt(0)-olefin coordination. The cross-linking can
      be reversed through the addition of 2-bis(diphenylphosphino)ethane (dppe), a
      strong bidentate ligand, which removes the platinum from the PI to form
      Pt(dppe)(2). The Pt(0) cross-linking of PI was studied with self-assembled
      cylindrical PI-b-PFS block copolymer micelles, where the cross-linking was found
      to dramatically increase the stability of the micellar structures. The Pt(0)
      alkene coordination-induced cross-linking can be used to provide transmission
      electron microscopy contrast between PI and poly(dimethylsiloxane) (PDMS) corona
      domains in block comicelles as the process selectively increases the electron
      density of the PI regions. Moreover, following the assembly of a hierarchical
      scarf-shaped comicelle consisting of a PFS-b-PDMS platelet template with PI-b-PFS
      tassels, Pt(0)-induced cross-linking of the PI coronal regions allowed for the
      selective removal of the PFS-b-PDMS center, leaving behind an unprecedented
      hollowed-out scarf structure. The addition of Karstedt's catalyst to PI or
      polybutadiene homopolymer toluene/xylene solutions resulted in the formation of
      polymer gels which underwent de-gelation upon the addition of dppe.

PMID- 21967616
TI  - Unmet needs of older people with asthma: cross-sectional survey.
AB  - INTRODUCTION: Asthma in older people is a major cause of disease burden in
      Australia and is projected to increase over the next two decades. Current
      guidelines for asthma care rely predominantly on studies from younger
      populations. METHODS: We undertook a cross-sectional survey of older people with
      asthma to identify their concerns and their perceived asthma symptom burden. One
      hundred and ninety-nine people over 55 years of age with asthma were recruited
      from community pharmacies, in the states of Victoria and NSW, Australia. RESULTS:
      One-hundred and twenty (62%) participants reported "perfectly" or "very well
      controlled" asthma over the past month, and 78% claimed adherence to asthma
      treatment. Despite this, 105 (55%) reported experiencing moderate to severe
      symptoms and 58 (30%) moderate to extreme restrictions on their lifestyle in the
      past month. Exacerbations were also common with over one-third of participants
      seeking emergency asthma care or requiring oral corticosteroids in the past 12
      months. In spite of 80% of participants reporting confidence of how to manage
      their asthma properly, only 10% said they would call an ambulance or visit an
      Emergency Department if their asthma was "out of control." Further asthma self
      management education was considered desirable by two-thirds. However, those over
      65 years preferred less autonomy in decision-making compared to those under 65
      years. CONCLUSION. Older people with asthma experience a high symptom burden. A
      simplified version of our questionnaire could assist GPs, specialists, and asthma
      educators to identify the individual needs of older patients and to tailor their
      delivery of asthma care accordingly.

PMID- 21967617
TI  - Reflux esophagitis after esophagectomy: impact of duodenogastroesophageal reflux.
AB  - Reflux esophagitis (RE) is a known complication disturbing patients' quality of
      life after esophageal resection. It is generally recognized that bile reflux as
      well as acid reflux cause RE. However, the clinical influence of acid and bile
      reflux, and Helicobacter pylori (H. pylori) infection on RE in the cervical
      esophagus after esophagectomy is not yet clarified. Sixty patients who underwent
      cervical esophagogastrostomy following esophagectomy were enrolled in this study.
      They underwent examination for H. pylori infection, endoscopic examination, and
      continuous 24-hour pH and bilirubin monitoring, at 1 month after surgery. The
      influence of acid and/or bile reflux, H. pylori infection, and others on the
      development of RE were investigated. RE was observed in 19 patients (32%) at 1
      month after esophagogastrostomy, mild RE in 16 (27%), and severe RE in 3 (5%).
      The percentage of time duration of both acid and bile reflux into the cervical
      esophagus was higher in patients with RE than in those without (P = 0.027, P <
      0.001). A significant difference in %time pH < 4 acid reflux was found between
      mild RE and severe RE (P = 0.014), and a statistical difference in %time abs. >
      0.14 between non-RE and mild RE (P = 0.017). Acid and/or bile reflux was observed
      in 31 patients (52%), acid-only reflux in 6 (10%), bile-only reflux in 15 (25%),
      and acid-and-bile reflux in 10 (17%). Severe RE was observed only in patients
      having acid-and-bile reflux. On the univariate analysis, no infection of H.
      pylori, acid reflux, and bile reflux were determined to be the influencing
      factors to RE among the clinical factors including age, gender, route of
      esophageal reconstruction, H. pylori infection, and acid-and-bile reflux. In the
      subanalysis using the logistic model, there were significant correlations between
      bile reflux and RE irrespective of the presence of H. pylori infection (P =
      0.016, P = 0.007). On the other hand, there was a significant correlation between
      acid reflux and RE only in patients without H. pylori infection (P = 0.039). In
      the early period after esophagogastrostomy, bile reflux could cause RE
      irrespective of H. pylori infection, while acid reflex could cause RE only in
      patients without H. pylori infection. There is a possibility that bile reflux
      plays an important role in the development of RE after esophagectomy.

PMID- 21967618
TI  - Microscopic colitis: clinical findings, topography and persistence of
      histopathological subgroups.
AB  - BACKGROUND: Uncertainty remains on topography and persistence of histological
      subgroups of microscopic colitis (MC). AIM: To assess longitudinal clinical,
      endoscopic, histological, and therapeutic description of MC subgroups including
      patients with incomplete findings of MC (MCi). METHODS: Retrospective review of a
      consecutive cohort with MC and histological reassessment of MCi. RESULTS:
      Clinical characteristics of 168 patients with lymphocytic colitis (LC), 270 with
      collagenous colitis (CC) and 101 with MCi were similar. At colonoscopy 95% (95%
      CI: 91-98%) of CC and 98% (93-100%) of LC cases had diagnostic histopathology of
      MC in both left and right colon. Eight and three patients had characteristics of
      MC only in the left and right colon, respectively. Histology findings resembling
      coexistence of the other MC subtype was present in 48% (40-55%) with CC and 24%
      (18-31%) with LC. A first diagnosis of MC was made in 49 (30%) of 164 patients
      only at repeat endoscopy. Another 34 of 115 (30%) with MC in the first endoscopy
      did not fulfil the MC criteria at repeat endoscopy. Only seven cases had a
      primary endoscopy without histopathological abnormalities. Fifteen percentage of
      MCi were reclassified as MC. Ileal inflammation was present in 33 of 81 patients.
      Budesonide was efficacious in all MC subgroups irrespective of bile acid
      malabsorption. CONCLUSIONS: Clinical characteristics of microscopic colitis
      subgroups are indistinguishable. Biopsies from the left colon suffice to exclude
      microscopic colitis, and the histological diagnosis of microscopic colitis is
      inconsistent over time. Ileal inflammation is common. The term microscopic
      colitis should perhaps be considered one clinical entity and include lymphocytic
      colitis, collagenous colitis, and incomplete findings of microscopic colitis.

PMID- 21967619
TI  - Autonomic self-healing lipid monolayer: a new class of ultrathin dielectric.
AB  - The electrical performance of stabilized lipid monolayers on H-terminated silicon
      is reported for the first time. We show that these 2.7 nm thick only ultrathin
      layers present extremely low current leakage at high electric field and high
      breakdown voltage that both compare favorably with the best data reported on
      organic thin film dielectrics. We demonstrate a very unique property of autonomic
      self-healing of the layer at room temperature with the total recovery of its
      performance after electrical breakdown. The mechanisms involved in breakdown and
      self-healing are described.

PMID- 21967620
TI  - Evaluation of the tear and serum levels of IL-8 in sulfur mustard intoxicated
      patients 20 years after exposure.
AB  - PURPOSE: Delayed keratitis is the most dangerous ocular complication of sulfur
      mustard (SM) exposure. This study aimed to evaluate the role of tear and serum
      levels of interleukin-8 (IL-8) in SM exposed subjects. DESIGN AND METHODS: In
      this historical cohort study, the experimental group included 370 participants
      who had been exposed to SM 20 years prior. Data were compared with those of 128
      unexposed participants as the control group. After completing a thorough systemic
      and ocular examination, serum IL-8 levels in all exposed and controls were
      compared. According to the statistical calculation, tear IL-8 levels, were
      compared in randomly selected 48 exposed and 37 controls. Based on the ocular
      findings, the selected subjects were divided into two subgroups, normal subjects
      include those participants who had no ocular signs and abnormal subjects, were
      those who had at least one or more ocular signs. RESULTS: Bulbar conjunctiva and
      limbal tissues evaluation in all participants showed a significantly higher
      number of abnormalities in exposed group than in the control group (P=0.004 and
      P=0.048 respectively). Serum IL-8 levels in all exposed were significantly lower
      than the matched controls (P=0.002). Tear IL-8 levels in the selected exposed
      were significantly lower than in the selected controls (P=0.030). In exposed
      group with normal conditions of the lids, bulbar conjunctiva, cornea, tear
      status, limbus, slit lamp findings and final ophthalmic assessment, tear IL-8
      levels were significantly lower than in the matched controls (P=0.022, 0.037,
      0.027, 0.050, 0.039, 0.029, 0.045 respectively). With respect to the global
      ophthalmic assessment, tear fluid IL-8 levels in the abnormal controls were
      significantly lower than in the normal controls (P=0.049), but this decrease in
      secretion of tear IL-8 were not encountered in abnormal exposed (P=0.415).
      CONCLUSION: Tear IL-8 secretion was significantly inhibited in the unexposed
      controls with ocular surface abnormalities, while these inhibitory responses were
      not encountered in SM-exposed cases with ocular surface abnormalities.

PMID- 21967621
TI  - Pacemaker (PM)/implantable cardioverter defibrillator lead masses.

PMID- 21967622
TI  - Noninvasive detection of concealed explosives: depth profiling through opaque
      plastics by time-resolved Raman spectroscopy.
AB  - The detection of explosives concealed behind opaque, diffusely scattering
      materials is a challenge that requires noninvasive analytical techniques for
      identification without having to manipulate the package. In this context, this
      study focuses on the application of time-resolved Raman spectroscopy (TRRS) with
      a picosecond pulsed laser and an intensified charge-coupled device (ICCD)
      detector for the noninvasive identification of explosive materials through
      several millimeters of opaque polymers or plastic packaging materials. By means
      of a short (250 ps) gate which can be delayed several hundred picoseconds after
      the laser pulse, the ICCD detector allows for the temporal discrimination between
      photons from the surface of a sample and those from deeper layers. TRRS was
      applied for the detection of the two main isomers of dinitrotoluene, 2,4
      dinitrotoluene, and 2,6-dinitrotoluene as well as for various other components of
      explosive mixtures, including akardite II, diphenylamine, and ethyl centralite.
      Spectra were obtained through different diffuse scattering white polymer
      materials: polytetrafluoroethylene (PTFE), polyoxymethylene (POM), and
      polyethylene (PE). Common packaging materials of various thicknesses were also
      selected, including polystyrene (PS) and polyvinyl chloride (PVC). With the
      demonstration of the ability to detect concealed, explosives-related compounds
      through an opaque first layer, this study may have important applications in the
      security and forensic fields.

PMID- 21967627
TI  - Adalimumab for psoriasis in Greece: clinical experience in a tertiary referral
      centre.
AB  - BACKGROUND: Adalimumab, a fully human, anti-TNFalpha monoclonal antibody has been
      shown to be effective for moderate-to-severe psoriasis in clinical trial setting.
      However, only a limited number of studies reflect everyday clinical experience
      with this drug. OBJECTIVES: To provide evidence on the efficacy, dose
      optimization and safety of adalimumab based on everyday clinical experience in a
      tertiary referral centre for psoriasis, in Greece. METHODS: We retrospectively
      reviewed the records of all patients with moderate-to-severe psoriasis who
      received adalimumab, in our referral centre, between January 2008 and October
      2010. RESULTS: In total, 52 patients were treated with adalimumab for a mean
      period of 14 months (range 4-30 months). Mean baseline Psoriasis Area and
      Severity Index (PASI) was 16.7 (range 9-40.3). At 4, 6, 12 and 18 months, PASI75
      was attained by 68%, 82%, 89% and 88% of patients respectively. Nineteen of 52
      patients (36%) reached a PASI100 at a mean time of 10 months (range 4-18 months).
      The dose interval between the injections of adalimumab was increased from 2 to 3
      weeks for 14 patients (27%) who achieved and sustained a PASI100 after the first
      year of treatment, without any relapse. The overall rate of adverse events
      reached 38%, but treatment was discontinued only in two cases (4%). CONCLUSIONS:
      Our study demonstrates that adalimumab is effective and safe in patients with
      moderate-to-severe psoriasis in short- and long-term setting. At the same time,
      it points out novel and interesting issues for further investigation.

PMID- 21967629
TI  - Renovascular resistance of machine-perfused DCD kidneys is associated with
      primary nonfunction.
AB  - Donation after cardiac death (DCD) has shown to be a valuable extension of the
      donor pool despite a higher percentage of primary nonfunction (PNF). Limiting the
      incidence of PNF is of vital importance. Renovascular resistance is believed to
      predict graft outcome; however the literature is inconsistent. Therefore, we
      studied whether renovascular resistance is associated with PNF and whether this
      parameter should be used to discard donor kidneys. All transplanted DCD kidneys
      preserved by machine perfusion at our center between 1993 and 2007 were analyzed
      (n = 440). The effects of renovascular resistance on PNF, delayed graft function
      (DGF), and graft and patient survival were examined using multivariable analyses;
      predictive quality by calculating the area under the curve (AUC). We showed that
      renovascular resistance at the start of machine perfusion was significantly and
      independently associated with PNF (OR 2.040, 95% CI 1.362-3.056; p = 0.001), and
      DGF (OR 2.345, 95% CI 1.110-4.955; p = 0.025). Predictive quality was moderate
      (0.609, 95% CI 0.538-0.681). Graft and patient survival were not associated with
      renovascular resistance. We conclude that renovascular resistance in DCD kidneys
      is an independent risk factor for PNF; however, the predictive value is
      relatively low.

PMID- 21967630
TI  - Cytotoxicity of Al2O3 nanoparticles at low exposure levels to a freshwater
      bacterial isolate.
AB  - The cytotoxicity of Al(2)O(3) nanoparticles (NP) at very low exposure levels (1
      MUg/mL and less) to a dominant bacterial isolate from freshwater (lake water),
      Bacillus licheniformis, was examined. Sterile lake water was directly used as a
      test medium or matrix to simulate the freshwater environment. Exposure to 1
      MUg/mL Al(2)O(3) NP for 2 h caused a 17% decrease in cell viability (as
      determined by plate count and MTT assay). During the test period, the particles
      were found to be stable against aggregation in the matrix and exerted a nano-size
      effect on the exposed test organisms. The decrease in cell viability was proven
      not to be due to the release of Al(3+) ions from the nanoparticles in the
      dispersion. The zeta potential and FT-IR analyses suggested that the surface
      charge based attachment of nanoparticles on to the bacterial cell wall was
      responsible for flocculation leading to toxicity. The cell wall damage confirmed
      through SEM and the lipid peroxidation assay also contributed toward toxicity.
      This study warns of possible ecotoxicity of nanoparticles even at environmentally
      relevant concentrations. However, detailed studies need to be carried out to
      establish probable mechanistic aspects of this low concentration toxicity
      phenomenon.

PMID- 21967631
TI  - Efficacy of omega-3 polyunsaturated fatty acids for the treatment of refractory
      hydroa vacciniforme.
AB  - Hydroa vacciniforme (HV) is a rare photodermatosis. Several therapies, with
      sometimes severe side effects, have been used in isolated cases. We report a case
      of refractory HV successfully treated with dietary fish oil rich in omega-3
      polyunsaturated fatty acids.

PMID- 21967628
TI  - Glucocorticoid and polyamine interactions in the plasticity of glutamatergic
      synapses that contribute to ethanol-associated dependence and neuronal injury.
AB  - Stress contributes to the development of ethanol dependence and is also a
      consequence of dependence. However, the complexity of physiological interactions
      between activation of the hypothalamic-pituitary-adrenal (HPA) axis and ethanol
      itself is not well delineated. Emerging evidence derived from examination of
      corticotropin-releasing factor systems and glucocorticoid receptor systems in
      ethanol dependence suggests a role for pharmacological manipulation of the HPA
      axis in attenuating ethanol intake, though it is not clear how activation of the
      HPA axis may promote ethanol dependence or contribute to the neuroadaptative
      changes that accompany the development of dependence and the severity of ethanol
      withdrawal. This review examines the role that glucocorticoids, in particular,
      have in promoting ethanol-associated plasticity of glutamatergic synapses by
      influencing expression of endogenous linear polyamines and polyamine-sensitive
      polypeptide subunits of N-methyl-D-aspartate (NMDA)-type glutamate receptors. We
      provide evidence that interactions among glucocorticoid systems, polyamines and
      NMDA receptors are highly relevant to both the development of ethanol dependence
      and to behavioral and neuropathological sequelae associated with ethanol
      withdrawal. Examination of these issues is likely to be of critical importance
      not only in further elucidating the neurobiology of HPA axis dysregulation in
      ethanol dependence, but also with regard to identification of novel therapeutic
      targets that may be exploited in the treatment of ethanol dependence.

PMID- 21967632
TI  - Gene expression profile of circulating tumor cells in breast cancer by RT-qPCR.
AB  - BACKGROUND: Circulating tumor cells (CTCs) have been associated with prognosis
      especially in breast cancer and have been proposed as a liquid biopsy for
      repeated follow up examinations. Molecular characterization of CTCs is difficult
      to address since they are very rare and the amount of available sample is very
      limited. METHODS: We quantified by RT-qPCR CK-19, MAGE-A3, HER-2, TWIST1, hTERT
      alpha+beta+, and mammaglobin gene transcripts in immunomagnetically positively
      selected CTCs from 92 breast cancer patients, and 28 healthy individuals. We also
      compared our results with the CellSearch system in 33 of these patients with
      early breast cancer. RESULTS: RT-qPCR is highly sensitive and specific and can
      detect the expression of each individual gene at the one cell level. None of the
      genes tested was detected in the group of healthy donors. In 66 operable breast
      cancer patients, CK-19 was detected in 42.4%, HER-2 in 13.6%, MAGE-A3 in 21.2%,
      hMAM in 13.6%, TWIST-1 in 42.4%, and hTERT alpha+beta+ in 10.2%. In 26 patients
      with verified metastasis, CK-19 was detected in 53.8%, HER-2 in 19.2%, MAGE-A3 in
      15.4%, hMAM in 30.8%, TWIST-1 in 38.5% and hTERT alpha+beta+in 19.2%. Our
      preliminary data on the comparison between RT-qPCR and CellSearch in 33 early
      breast cancer patients showed that RT-qPCR gives more positive results in respect
      to CellSearch. CONCLUSIONS: Molecular characterization of CTCs has revealed a
      remarkable heterogeneity of gene expression between breast cancer patients. In a
      small percentage of patients, CTCs were positive for all six genes tested, while
      in some patients only one of these genes was expressed. The clinical significance
      of these findings in early breast cancer remains to be elucidated when the
      clinical outcome for these patients is known.

PMID- 21967633
TI  - Nanoconfinement of spider silk fibrils begets superior strength, extensibility,
      and toughness.
AB  - Silk is an exceptionally strong, extensible, and tough material made from simple
      protein building blocks. The molecular structure of dragline spider silk repeat
      units consists of semiamorphous and nanocrystalline beta-sheet protein domains.
      Here we show by a series of computational experiments how the nanoscale
      properties of silk repeat units are scaled up to create macroscopic silk fibers
      with outstanding mechanical properties despite the presence of cavities, tears,
      and cracks. We demonstrate that the geometric confinement of silk fibrils to
      diameters of 50 +/- 30 nm is critical to facilitate a powerful mechanism by which
      hundreds of thousands of protein domains synergistically resist deformation and
      failure to provide enhanced strength, extensibility, and toughness at the
      macroscale, closely matching experimentally measured mechanical properties.
      Through this mechanism silk fibers exploit the full potential of the nanoscale
      building blocks, regardless of the details of microscopic loading conditions and
      despite the presence of large defects. Experimental results confirm that silk
      fibers are composed of silk fibril bundles with diameters in the range of 20-150
      nm, in agreement with our predicted length scale. Our study reveals a general
      mechanism to map nanoscale properties to the macroscale and provides a potent
      design strategy toward novel fiber and bulk nanomaterials through hierarchical
      structures.

PMID- 21967634
TI  - Immunogenicity of meningococcus C vaccination in a patient with atypical
      hemolytic uremic syndrome (aHUS) on eculizumab therapy.
AB  - We report successful kidney transplantation in a 10-yr-old boy with aHUS and
      heterozygous factor H mutation using the terminal complement inhibitor eculizumab
      to avoid recurrence of aHUS in the renal graft. Vaccination against meningococcus
      C (Men C) is essential in patients with dysfunction of the complement system, as
      induced by eculizumab. In our patient, we report waning SBA titers but
      maintenance of protective SBA titers (>=1:8) after kidney transplantation under
      immunosuppressive therapy with mycophenolate mofetil, tacrolimus, steroids, and
      eculizumab over a 27-month observational period. Our case illustrates that a
      humoral immune response to conjugate Men C vaccination may be mounted and
      maintained despite chronic renal disease, kidney transplantation,
      immunosuppressive drugs, and immunomodulatory therapy with eculizumab. However,
      it remains unclear whether serologically defined protective SBA titers mediate
      true protection from invasive meningococcal disease in an immunocompromised
      patient, particularly under treatment with a complement inhibitor. Thus, close
      monitoring of SBA titers seems mandatory in this patient.

PMID- 21967635
TI  - Structure of the molten salt methyl ammonium nitrate explored by experiments and
      theory.
AB  - We present an analysis of the structure of the monomethylammonium nitrate (MMAN)
      compound. Vibrational Raman spectroscopy and X-ray powder diffraction have been
      used to characterize the bulk phases of MMAN, and assignment of the resonant
      frequencies has been performed by ab initio (DFT) computations on small clusters
      of the compound. The theoretical spectra are in excellent agreement with the
      experimental ones and provide a means by which an interpretation of the hydrogen
      bonding network that exists in such compound can be analyzed. In particular, we
      found that the spectrum of one of the solid phases is structurally very similar
      to that of the liquid. We present experimental evidence for the existence of such
      phase both from X-ray data and Raman spectra which, in turn, is easily
      interpreted with a one-to-one correspondence with the ab initio simulation of the
      small clusters. A geometric structure of the short-range local arrangement in
      these two bulk phases is therefore proposed.

PMID- 21967636
TI  - Comparison of photosynthetic components of wheat genotypes under rain-fed and
      irrigated conditions.
AB  - The major environmental factor limiting the range of adaptation for wheat is
      drought. Fourteen wheat genotypes (Triticum aestivum L.) were grown under two
      environments (irrigated and rain fed) to determine physiological and
      photosynthetic responses to drought. Combined analysis of variance of the data
      showed that the environment was a significant source of variation for leaf
      chlorophyll content (LCC), stomatal conductance (g(s)) and grain yield (GY).
      Wheat genotypes differed significantly for LCC, g(s) and GY. All the measured
      traits under water-stress conditions except maximum photochemical efficiency of
      PSII (F(v)/F(m)) were lower than those under nonstress conditions. Mean GY in
      rain-fed conditions was 11.26% lower than that in irrigated conditions. The
      genotypes number 13 (Marvdasht) and 8 (M-81-13) exhibited the highest GY per unit
      area in both irrigation and rain-fed conditions. It was concluded that the higher
      LCC and g(s) under drought-stress conditions could possibly be the proper
      criteria for screening the drought-tolerant wheat genotypes under field
      conditions.

PMID- 21967637
TI  - Characterization of Danio rerio Nanog and functional comparison to Xenopus Vents.
AB  - Nanog is a homeodomain transcription factor associated with the acquisition of
      pluripotency. Genome analyses of lower and higher vertebrates revealed that the
      existence of Nanog is restricted to gnathostomata but absent from agnatha and
      invertebrates. To elucidate the function of Nanog in nonmammalia, we identified
      the Danio rerio ortholog of Nanog and characterized its role in gain and loss of
      function experiments. We found Nanog to be crucial for survival of early
      zebrafish embryos, because depletion of Nanog led to gastrulation defects with
      subsequent lethality. Mouse Nanog overexpression could rescue these defects. Vice
      versa, zebrafish Nanog was found to promote proliferation and to inhibit
      differentiation of mouse embryonic stem cells in the absence of leukemia
      inhibitory factor. These findings indicate functional conservation of Nanog from
      teleost fishes to mammals. However, Nanog was lost in the genome of the anurans
      Xenopus laevis and Xenopus tropicalis. Phylogenetic analysis revealed that
      deletion probably occurred in a common anuran ancestor along with chromosomal
      translocations. The closest homologs of Nanog in Xenopus are the Vent proteins.
      We, therefore, investigated whether the Xvent genes might substitute for Nanog
      function in Xenopus. Although we found some similarities in phenotypes after
      overexpression and in the regulation of several marker genes, Xvent1/2 and Nanog
      cannot substitute each other. Depletion of Nanog in zebrafish cannot be rescued
      by ectopic expression of Xvent, and Xvent depletion in Xenopus cannot be overcome
      by ectopic expression of zebrafish Nanog.

PMID- 21967638
TI  - Bone morphogenetic protein-2-induced signaling and osteogenesis is regulated by
      cell shape, RhoA/ROCK, and cytoskeletal tension.
AB  - Osteogenic differentiation of human mesenchymal stem cells (hMSCs) is classically
      thought to be mediated by different cytokines such as the bone morphogenetic
      proteins (BMPs). Here, we report that cell adhesion to extracellular matrix
      (ECM), and its effects on cell shape and cytoskeletal mechanics, regulates BMP
      induced signaling and osteogenic differentiation of hMSCs. Using micropatterned
      substrates to progressively restrict cell spreading and flattening against ECM,
      we demonstrated that BMP-induced osteogenesis is progressively antagonized with
      decreased cell spreading. BMP triggered rapid and sustained RhoA/Rho-associated
      protein kinase (ROCK) activity and contractile tension only in spread cells, and
      this signaling was required for BMP-induced osteogenesis. Exploring the molecular
      basis for this effect, we found that restricting cell spreading, reducing ROCK
      signaling, or inhibiting cytoskeletal tension prevented BMP-induced SMA/mothers
      against decapentaplegic (SMAD)1 c-terminal phosphorylation, SMAD1 dimerization
      with SMAD4, and SMAD1 translocation into the nucleus. Together, these findings
      demonstrate the direct involvement of cell spreading and RhoA/ROCK-mediated
      cytoskeletal tension generation in BMP-induced signaling and early stages of in
      vitro osteogenesis, and highlight the essential interplay between biochemical and
      mechanical cues in stem cell differentiation.

PMID- 21967639
TI  - Race and older mothers' differentiation: a sequential quantitative and
      qualitative analysis.
AB  - The goal of this paper is to demonstrate a process by which qualitative and
      quantitative approaches are combined to reveal patterns in the data that are
      unlikely to be detected and confirmed by either method alone. Specifically, we
      take a sequential approach to combining qualitative and quantitative data to
      explore race differences in how mothers differentiate among their adult children.
      We began with a standard multivariate analysis examining race differences in
      mothers' differentiation among their adult children regarding emotional closeness
      and confiding. Finding no race differences in this analysis, we conducted an in
      depth comparison of the Black and White mothers' narratives to determine whether
      there were underlying patterns that we had been unable to detect in our first
      analysis. Using this method, we found that Black mothers were substantially more
      likely than White mothers to emphasize interpersonal relationships within the
      family when describing differences among their children. In our final step, we
      developed a measure of familism based on the qualitative data and conducted a
      multivariate analysis to confirm the patterns revealed by the in-depth comparison
      of the mothers' narratives. We conclude that using such a sequential mixed
      methods approach to data analysis has the potential to shed new light on complex
      family relations.

PMID- 21967641
TI  - Testing DNA barcoding in closely related groups of Lysimachia L. (Myrsinaceae).
AB  - It has been suggested that rbcL and matK are the core barcodes in plants, but
      they are not powerful enough to distinguish between closely related plant groups.
      Additional barcodes need to be evaluated to improve the level of discrimination
      between plant species. Because of their well-studied taxonomy and extreme
      diversity, we used Chinese Lysimachia (Myrsinaceae) species to test the
      performance of core barcodes (rbcL and matK) and two additional candidate
      barcodes (trnH-psbA and the nuclear ribosomal ITS); 97 accessions from four
      subgenus representing 34 putative Lysimachia species were included in this study.
      And many closely related species pairs in subgen. Lysimachia were covered to
      detect their discriminatory power. The inefficiency of rbcL and matK alone or
      combined in closely related plant groups was validated in this study. TrnH-psbA
      combined with rbcL + matK did not yet perform well in Lysimachia groups. In
      contrast, ITS, alone or combined with rbcL and/or matK, revealed high resolving
      ability in Lysimachia. We support ITS as a supplementary barcode on the basis of
      core barcode rbcL and matK. Besides, this study also illustrates several mistakes
      or underlying evolutionary events in Lysimachia detected by DNA barcoding.

PMID- 21967642
TI  - Advances in allogeneic stem cell transplantation for hemoglobinopathies.
AB  - Hematopoietic stem cell transplantation (SCT) is currently the only potential
      curative therapy for thalassemia and sickle cell disease. A myeloablative
      conditioning regimen has been in use to eradicate the disease. Nowadays, improved
      preparative and conditioning methods are used including reduced intensity
      conditioning regimens. Such developments have allowed transplantation of more
      advanced hemoglobinopathy diseases. Stem cell transplant sources became more
      accessible including umbilical cord blood and alternate donor. However, donor
      human leukocyte antigen (HLA) disparity still carries a significant risk of
      morbidity and mortality.

PMID- 21967643
TI  - Influence of protein histidine phosphatase overexpression and down-regulation on
      human umbilical-vein endothelial cell viability.
AB  - PHP (protein histidine phosphatase) is expressed by mammalian tissues,
      particularly in blood vessel walls. We investigated whether PHP plays a
      significant role in endothelial cells. By Western blot and immunofluorescence
      analysis PHP was found in HUVEC (human umbilical-vein endothelial cells).
      Overexpression of PHP by the use of a plasmid vector, pIRES2-AcGFP1-PHP, induced
      apoptosis in HUVEC. To exclude the possibility that increased cellular protein
      alone unspecifically caused cell damage, the inactive H53A mutant of PHP was also
      overexpressed as a control; it did not lead to apoptosis. Down-regulation of PHP
      by the RNAi (RNA interference) technique did not affect cell viability. In
      conclusion, HUVEC are damaged by overexpression, but not down-regulation, of PHP,
      suggesting a pronounced impact of the enzyme on the cells when its activity is
      increased.

PMID- 21967644
TI  - A preliminary experience with minimally invasive Ivor Lewis esophagectomy.
AB  - With several small series examining minimally invasive Ivor Lewis
      esophagectomies, we look to contribute to a growing experience. In reporting our
      initial results, safety, initial oncologic completeness, and preliminary outcomes
      with a minimally invasive Ivor Lewis esophagectomy were demonstrated. From 2007
      to 2010, 40 minimally invasive Ivor Lewis esophagectomies were carried out. The
      approach was a laparoscopic mobilization of the stomach and a thoracoscopic
      esophageal mobilization and creation of a high intrathoracic anastomosis.
      Indications included esophageal cancer in 39 patients and esophageal
      gastrointestinal stromal tumor in one patient. Median age was 62 (range 39-77)
      with 31 (78%) male patients. Non-emergent conversion was required in two (5%)
      patients. Twenty-five (63%) patients underwent neoadjuvant therapy. Mean
      operative time was 364 minutes (range 285-455), and mean blood loss was 205 cc
      (range 100-400). All patients underwent an R0 resection including the removal of
      all Barrett's esophagus, and mean number of nodes harvested was 21 (range 11-41).
      Median intensive care unit stay was 1 day (range 1-3), and hospital stay was 7
      days (range 6-19). There were no anastomotic leaks and no 30-day mortality.
      Postoperative complications included eight (21%) patients with atrial
      fibrillation and two (5%) chylothorax, one requiring ligation. At a mean follow
      up of 16.5 months (range 1-39 months), five (13%) patients have had a distant
      recurrence; there have been no local recurrences. Minimally invasive Ivor Lewis
      esophagectomy, although technically challenging, can be carried out with
      reasonable operative times, a short length of stay, and minimal complication.
      Final oncologic validity is pending longer follow-up and a larger series.

PMID- 21967640
TI  - Mitochondrial regulation of cell cycle and proliferation.
AB  - Eukaryotic mitochondria resulted from symbiotic incorporation of alpha
      proteobacteria into ancient archaea species. During evolution, mitochondria lost
      most of the prokaryotic bacterial genes and only conserved a small fraction
      including those encoding 13 proteins of the respiratory chain. In this process,
      many functions were transferred to the host cells, but mitochondria gained a
      central role in the regulation of cell proliferation and apoptosis, and in the
      modulation of metabolism; accordingly, defective organelles contribute to cell
      transformation and cancer, diabetes, and neurodegenerative diseases. Most cell
      and transcriptional effects of mitochondria depend on the modulation of
      respiratory rate and on the production of hydrogen peroxide released into the
      cytosol. The mitochondrial oxidative rate has to remain depressed for cell
      proliferation; even in the presence of O2, energy is preferentially obtained from
      increased glycolysis (Warburg effect). In response to stress signals, traffic of
      pro- and antiapoptotic mitochondrial proteins in the intermembrane space (B-cell
      lymphoma-extra large, Bcl-2-associated death promoter, Bcl-2 associated X-protein
      and cytochrome c) is modulated by the redox condition determined by mitochondrial
      O2 utilization and mitochondrial nitric oxide metabolism. In this article, we
      highlight the traffic of the different canonical signaling pathways to
      mitochondria and the contributions of organelles to redox regulation of kinases.
      Finally, we analyze the dynamics of the mitochondrial population in cell cycle
      and apoptosis.

PMID- 21967645
TI  - Lack of significant food effect on the pharmacokinetics of ticagrelor in healthy
      volunteers.
AB  - WHAT IS KNOWN AND OBJECTIVE: Ticagrelor is the first reversibly binding oral
      P2Y(12) receptor antagonist and has been approved in the European Union and the
      USA for the reduction of clinical thrombotic events in patients with acute
      coronary syndromes. This study aimed to assess the effect of food on ticagrelor
      pharmacokinetics. METHODS: The study was an open-label, randomized, 2-period
      crossover single-centre trial; 26 healthy volunteers received a single 270 mg
      (3*90 mg tablets) ticagrelor dose orally following: (i) a 10-h overnight fast;
      and (ii) after a standard high-fat, high-calorie breakfast. Ticagrelor and AR
      C124910XX (a major pharmacologically active metabolite) plasma concentrations
      were quantified for pharmacokinetic analysis. RESULTS: Ticagrelor median time to
      maximum concentration (t(max); 2.5 h vs. 1.5 h) was slightly delayed in the fed
      vs. fasting state. Maximum concentration of ticagrelor (C(max)) was comparable
      between the two states with 95% confidence intervals (CI) of the geometric least
      squares (GLS) mean ratio (0.85-1.03) being within no-effect limits (0.80-1.25).
      Ticagrelor exposure was slightly higher with food intake; area under the plasma
      concentration-time curve from zero to infinity (AUC) was 21% higher compared with
      fasting state (95% CI of GLS mean ratio=1.13-1.30). For AR-C124910XX, AUC (95% CI
      of GLS mean ratio=0.93-1.07) was unaffected by food consumption. Median t(max) of
      the metabolite was slightly longer in the fed than fasting state (3.5 h vs. 1.5
      h). Mean C(max) for AR-C124910XX was slightly lower (22%) with food intake vs.
      fasting (95% CI of GLS mean ratio 0.69-0.88). WHAT IS NEW AND CONCLUSION: Food
      effects on ticagrelor AUC and AR-C124910XX C(max) were small and are considered
      to be of minimal clinical significance. Thus, ticagrelor can be administered with
      or without food.

PMID- 21967646
TI  - Analysis of the deep digital flexor tendon in rats submitted to stretching after
      immobilization.
AB  - Few studies have analyzed the effect of stretching after immobilization on the
      structural and biochemical properties of tendons. Here, the effect of stretching
      and immobilization on the proximal (p), intermediate (i), and distal (d) regions
      of the deep digital flexor tendon in rats was analyzed. The d region was
      subjected to compression and tension forces, the i region was subjected to
      compressive forces and the p region received tension forces. Rats were separated
      into five groups: GI--control for GII; GII--immobilized rats; GIII--control for
      GIV and GV groups; GIV--immobilized and stretched rats; and GV--immobilized rats
      which were allowed free cage activity. GII showed a higher molecular organization
      in the d and p regions as detected by measuring optical retardation, a lower
      concentration of hydroxyproline in the i region and a significant decrease in
      noncollagenous proteins found in the three regions of the tendon. Regarding the
      glycosaminoglycans, diminishing dermatan sulfate and the absence of chondroitin
      sulfate in the i region were observed in GII when compared to GI. However, in the
      same region of GIV, higher concentrations of chondroitin and dermatan sulfate
      were observed along with a strong metachromasy. An increase in hydroxyproline
      content in the i region and a higher molecular organization in the d and p
      regions were observed in GIV. Apparently, the active isoforms of
      metalloproteinase-2 also increased after stretching in all regions. These results
      suggest that stretching after immobilization contributed to the increase in
      molecular organization and to the synthesis of extracellular matrix components.

PMID- 21967647
TI  - Surface-enhanced Raman scattering spectroscopy of explosive 2,4-dinitroanisole
      using modified silver nanoparticles.
AB  - 2,4-Dinitroanisole (DNAN) is being used as a replacement for 2,4,6
      trinitrotoluene (TNT) as a less-sensitive melt-cast medium explosive than TNT. In
      this paper, we studied the surface-enhanced Raman spectroscopy (SERS) analysis of
      DNAN using Ag nanoparticles (AgNPs) modified by L-cysteine methyl ester
      hydrochloride. Due to the formation of a Meisenheimer complex between DNAN and
      the modifier, the modified AgNPs can detect 20 MUg/L (0.2 ng) and 0.1 mg/L (1 ng)
      DNAN in deionized water and aged tap water, respectively. Three other chemicals
      (L-cysteine, N-acetyl-L-cysteine, and L-cysteine ethyl ester hydrochloride) were
      used as AgNPs modifiers to study the mechanism of the SERS of DNAN. It was
      confirmed that the amino group of L-cysteine methyl ester hydrochloride was the
      active group and that the methyl ester group significantly contributed to the
      high SERS sensitivity of DNAN. In order to further test the mechanism of
      Meisenheimer complex formation, the effect of anions and cations present in
      natural water on the SERS of DNAN was studied. It was found that CO(3)(2-), Cl(
      ), and K(+) at 100 mg/L did not negatively affect the SERS of 10 mg/L DNAN, while
      SO(4)(2-), Na(+), Mg(2+), and Ca(2+) at 100 mg/L significantly quenched the SERS
      of 10 mg/L DNAN. The negative effect of the bivalent cations could be offset by
      SO(4)(2-).

PMID- 21967648
TI  - Microarray analysis reveals increased expression of DeltaNp63alpha in seborrhoeic
      keratosis.
AB  - BACKGROUND: Seborrhoeic keratoses (SKs) are very common benign epidermal lesions
      without malignant potential. Ultraviolet radiation, old age and viruses are well
      known risk factors for disease development. However, the pathomechanisms of SK
      are not fully understood. OBJECTIVES: To detect and characterize the genes that
      are involved in the pathogenesis of SK. METHODS: We performed a gene expression
      study using paired lesional and nonlesional skin samples from patients with SK.
      RESULTS: We identified and validated 19 differentially expressed genes in SK. Of
      these 19 genes, we focused on p63 transcription factor, which plays a pivotal
      role in epidermal development by regulating its transcriptional programme. We
      found by immunofluorescence that the expression of DeltaNp63alpha, the most
      abundantly expressed p63 isoform, was significantly increased in SK as compared
      with normal skin. Moreover, siRNA-mediated knockdown of DeltaNp63 led to the
      downregulation of 11 genes, including a member of the tensin family TNS4.
      Chromatin immunoprecipitation assay revealed that TNS4 was a target gene of p63.
      CONCLUSIONS: We identified upregulated genes in SK using genome-wide cDNA
      microarray and elucidated the functional contribution of p63 to the disease
      transcriptome by gene-silencing assay. Taken together, these data may provide a
      novel insight into the molecular basis of these benign skin lesions.

PMID- 21967653
TI  - An unusual cause of irregularly irregular supraventricular tachycardia.

PMID- 21967654
TI  - Nevus of Ota: morphological patterns and distribution in 47 Yemeni cases.
AB  - BACKGROUND: Nevus of Ota is a rare pigmentary disorder characterized by
      melanocytic hamartoma of the skin along the distribution of trigeminal nerve
      branches. AIM: To study the morphological features of nevus of Ota, and their
      relation with facial regions and trigeminal branches areas. METHODS: Patients
      with nevus of Ota who attended Kuwait University Hospital dermatology clinic and
      a private dermatology clinic in Sana'a, Yemen, between January 2008 and December
      2010, were clinically evaluated. The morphology of nevus of Ota was classified to
      homogenous, speckled or mixed. The distribution of the lesions was assessed based
      on both facial regions and areas supplied by the trigeminal nerve. RESULTS: Forty
      seven patients with nevus of Ota (F = 38, M = 9) were evaluated. Eighty percent
      of patients were females. Mixed (homogenous and speckled) appearance was seen in
      47% of all patients. Periocular region was the most commonly affected facial
      region (67%), and the maxillary area was the most commonly involved trigeminal
      branch area (94%). Forty-seven percent of cases had scleral pigmentation.
      Interesting features of nevus of Ota involving the nasal septum and crossing the
      midline of the face were noted. CONCLUSIONS: To the best of our knowledge, this
      is the first study that examines the distribution and morphology of nevus of Ota
      in Middle Eastern population. Including the morphological appearance of the nevus
      is practical and more clinically descriptive, and therefore should be integrated
      in the classification in future studies.

PMID- 21967655
TI  - Comprehensive profiling of free and conjugated estrogens by capillary
      electrophoresis-time of flight/mass spectrometry.
AB  - The biological activity of estrogens is tightly regulated by regioselective phase
      I/II metabolic transformations that are critical to human health. Current methods
      for analysis of urinary estrogens are limited by complicated sample pretreatment
      and/or inadequate specificity for free estrogens and their glucuronide/sulfate
      conjugates that vary widely in their intrinsic polarity. In this work, direct
      speciation of intact estrogen conjugates and their regioisomers is demonstrated
      using capillary electrophoresis-time-of-flight/mass spectrometry (CE-TOF/MS) when
      using an alkaline buffer system with negative ion mode detection. This method
      allows for resolution of weakly acidic native estrogens, anionic estrogen
      conjugates and their positional isomers without significant matrix-induced ion
      suppression effects in human urine. Identification of unknown estrogen
      metabolites using CE-TOF/MS is supported by accurate mass together with their
      characteristic relative migration times, which can be predicted based on two
      intrinsic physicochemical properties of an ion. CE-TOF/MS offers a promising
      strategy for comprehensive profiling of estrogens and other classes of steroid
      conjugates that is needed for deeper insight into the etiology and treatment of
      chronic disorders associated with impaired estrogen metabolism.

PMID- 21967656
TI  - Transthoracic echocardiography guidance during percutaneous closure of patent
      foramen ovale.
AB  - BACKGROUND: Percutaneous closure of patent foramen ovale (PFO) has been
      increasingly performed for several indications; mostly due to cryptogenic stroke.
      In this study we aimed to evaluate the safety and efficacy of transthoracic
      echocardiographic (TTE) guidance during percutaneous closure of PFO in using the
      Amplatzer and Occlutech Figulla PFO occluder devices. METHODS: Between October
      2005 and March 2011, 139 patients (74 male, mean age: 40.4 +/- 10.3) underwent
      transcatheter PFO closure. In all patients transesophageal echocardiography
      performed subsequently to diagnose, assess the size and evaluate for suitability
      of the defect for percutaneous closure. During the procedure fluoroscopy and TTE
      were used for guidance. RESULTS: Among 139 patients, Amplatzer PFO occluder was
      used in 74 patients and in 65 of them Occlutech Figulla device was selected for
      occlusion. The indications for PFO closure were ischemic stroke in 98 (70.5%),
      recurrent transient ischemic attacks (TIA) in 40 (28.7%), peripheral embolism in
      1 (0.8%) of the patients. In all patients, percutaneous intervention was
      performed successfully under TTE guidance. There have been no neurologic
      (recurrent strokes or TIAs) and cardiovascular complications during the immediate
      and long-term follow-up period (2-67 months, median 29). There was significant
      difference between the mean fluoroscopic time from the beginning which is 8.6 +/-
      3.4 min in the former versus 3.4 +/- 1.9 min in the latter (P < 0.05).
      CONCLUSION: Our study confirms the efficacy and safety of TTE guidance during
      percutaneous closure of PFO, which shortens the procedural time and obviates the
      need for general anesthesia or endotracheal intubation.

PMID- 21967657
TI  - Systemic treatment of pediatric atopic dermatitis with azathioprine and
      mycophenolate mofetil.
AB  - Severe forms of atopic dermatitis (AD) cause significant morbidity in vulnerable
      pediatric populations and necessitate treatment with systemic therapy. The
      existing literature concerning the treatment of severe pediatric AD with
      azathioprine (AZ) and mycophenolate mofetil (MM) is sparse. The purpose of this
      case series is to examine the use of these two drugs in the treatment of severe
      pediatric AD. Medical records of 28 pediatric patients with AD from the
      University of North Carolina at Chapel Hill pediatric dermatology clinic treated
      using these two drugs were analyzed for laboratory values, thiopurine
      methyltransferase (TPMT) levels, symptoms, infections, and other relevant data.
      Patients were also contacted via the telephone to ascertain outcomes and any
      missing data. Treatment outcomes were scored into three categories: significant
      improvement, some improvement, and no improvement. AZ dosing was correlated to
      TPMT levels successfully, with comparable levels of improvement in the
      heterozygous and homozygous wild-type groups. Absolute eosinophil count
      corresponded to AD activity and treatment response across both treatment
      modalities in 18 of 26 (69%) patients. Seventeen of 28 (61%) patients treated
      with AZ and eight of 12 (66%) treated with MM reported significant improvement.
      We had lower rates of laboratory abnormalities and side effects with MM than with
      AZ but similar rates of cutaneous infections. Treatment outcomes did not appear
      to differ with race, sex, or TPMT level. We experienced success with AZ and MM in
      the treatment of severe pediatric AD. Coordinating treatment to each patient's
      unique morbidities is the best way to choose systemic treatments.

PMID- 21967658
TI  - Missing and accounted for: gaps and areas of wealth in the public health review
      literature.
AB  - BACKGROUND: High-quality review evidence is useful for informing and influencing
      public health policy and practice decisions. However, certain topic areas lack
      representation in terms of the quantity and quality of review literature
      available. The objectives of this paper are to identify the quantity, as well as
      quality, of review-level evidence available on the effectiveness of public health
      interventions for public health decision makers. METHODS: Searches conducted on
      http://www.health-evidence.ca produced an inventory of public health review
      literature in 21 topic areas. Gaps and areas of wealth in the review literature,
      as well as the proportion of reviews rated methodologically strong, moderate, or
      weak were identified. The top 10 topic areas of interest for registered users and
      visitors of http://www.health-evidence.ca were extracted from user profile data
      and Google Analytics. RESULTS: Registered users' top three interests included: 1)
      healthy communities, 2) chronic diseases, and 3) nutrition. The top three
      preferences for visitors included: 1) chronic diseases, 2) physical activity, and
      3) addiction/substance use. All of the topic areas with many (301+) available
      reviews were of interest to registered users and/or visitors (mental health,
      physical activity, addiction/substance use, adolescent health, child health,
      nutrition, adult health, and chronic diseases). Conversely, the majority of
      registered users and/or visitors did not have preference for topic areas with few
      (<= 150) available reviews (food safety and inspection, dental health,
      environmental health) with the exception of social determinants of health and
      healthy communities. Across registered users' and visitors' topic areas of
      preference, 80.2% of the reviews were of well-done methodological quality, with
      43.5% of reviews having a strong quality rating and 36.7% a moderate review
      quality rating. CONCLUSIONS: In topic areas in which many reviews are available,
      higher level syntheses are needed to guide policy and practice. For other topic
      areas with few reviews, it is necessary to determine whether primary study
      evidence exists, or is needed, so that reviews can be conducted in the future.
      Considering that less than half of the reviews available on http://www.health
      evidence.ca are of strong methodological quality, the quality of the review-level
      evidence needs to improve across the range of public health topic areas.

PMID- 21967659
TI  - High incidence of anticytomegalovirus drug resistance among D+R- kidney
      transplant recipients receiving preemptive therapy.
AB  - Anti-cytomegalovirus (CMV) prophylaxis is recommended in D+R- kidney transplant
      recipients (KTR), but is associated with a theoretical increased risk of
      developing anti-CMV drug resistance. This hypothesis was retested in this study
      by comparing 32 D+R- KTR who received 3 months prophylaxis (valganciclovir) with
      80 D+R- KTR who received preemptive treatment. The incidence of CMV infections
      was higher in the preemptive group than in the prophylactic group (60% vs. 34%,
      respectively; p = 0.02). Treatment failure (i.e. a positive DNAemia 8 weeks after
      the initiation of anti-CMV treatment) was more frequent in the preemptive group
      (31% vs. 3% in the prophylactic group; p = 0.001). Similarly, anti-CMV drug
      resistance (UL97 or UL54 mutations) was also more frequent in the preemptive
      group (16% vs. 3% in the prophylactic group; p = 0.05). Antiviral treatment
      failures were associated with anti-CMV drug resistance (p = 0.0001). Patients
      with a CMV load over 5.25 log(10)  copies/mL displayed the highest risk of
      developing anti-CMV drug resistance (OR = 16.91, p = 0.0008). Finally, the 1-year
      estimated glomerular filtration rate was reduced in patients with anti-CMV drug
      resistance (p = 0.02). In summary, preemptive therapy in D+R- KTR with high CMV
      loads and antiviral treatment failure was associated with a high incidence of
      anti-CMV drug resistance.

PMID- 21967660
TI  - Proteolytically stable cancer targeting peptides with high affinity for breast
      cancer cells.
AB  - Cancer cell targeting peptides have emerged as a highly efficient approach for
      selective delivery of chemotherapeutics and diagnostics to different cancer
      cells. However, the use of alpha-peptides in pharmaceutical applications is
      hindered by their enzymatic degradation and low bioavailability. Starting with a
      10-mer alpha-peptide 18 that we developed previously, here we report three novel
      analogues of 18 that are proteolytically stable and display better (up to 3.5
      fold) affinity profiles for breast cancer cells compared to 18. The design
      strategy involved replacement of two or three amino acids in the sequence of 18
      with d-residues or beta(3)-amino acids. Such replacement maintained the
      specificity for cancer cells (MDA-MB-435, MDA-MB-231, and MCF-7) with low
      affinity for control noncancerous cells (MCF-10A and HUVEC), showed an increase
      in secondary structure, and rendered the analogues completely stable to human
      serum and liver homogenate from mice. The three analogues are potentially safe
      with minimal cellular toxicity and are efficient targeting moieties for specific
      drug delivery to breast cancer cells. The strategy used here may be adapted to
      develop peptide analogues that will target other cancer cell types.

PMID- 21967661
TI  - Structural studies of the PARP-1 BRCT domain.
AB  - BACKGROUND: Poly(ADP-ribose) polymerase-1 (PARP-1) is one of the first proteins
      localized to foci of DNA damage. Upon activation by encountering nicked DNA, the
      PARP-1 mediated trans-poly(ADP-ribosyl)ation of DNA binding proteins occurs,
      facilitating access and accumulation of DNA repair factors. PARP-1 also auto-(ADP
      ribosyl)ates its central BRCT-containing domain forming part of an interaction
      site for the DNA repair scaffolding protein X-ray cross complementing group 1
      protein (XRCC1). The co-localization of XRCC1, as well as bound DNA repair
      factors, to sites of DNA damage is important for cell survival and genomic
      integrity. RESULTS: Here we present the solution structure and biophysical
      characterization of the BRCT domain of rat PARP-1. The PARP-1 BRCT domain has the
      globular alpha/beta fold characteristic of BRCT domains and has a thermal melting
      transition of 43.0 degrees C. In contrast to a previous characterization of this
      domain, we demonstrate that it is monomeric in solution using both gel-filtration
      chromatography and small-angle X-ray scattering. Additionally, we report that the
      first BRCT domain of XRCC1 does not interact significantly with the PARP-1 BRCT
      domain in the absence of ADP-ribosylation. Moreover, none of the interactions
      with other longer PARP-1 constructs which previously had been demonstrated in a
      pull-down assay of mammalian cell extracts were detected. CONCLUSIONS: The PARP-1
      BRCT domain has the conserved BRCT fold that is known to be an important
      protein:protein interaction module in DNA repair and cell signalling pathways.
      Data indicating no significant protein:protein interactions between PARP-1 and
      XRCC1 likely results from the absence of poly(ADP-ribose) in one or both binding
      partners, and further implicates a poly(ADP-ribose)-dependent mechanism for
      localization of XRCC1 to sites of DNA damage.

PMID- 21967662
TI  - Using mobile phones to measure adolescent diabetes adherence.
AB  - OBJECTIVES: 1) describe and determine the feasibility of using cell-phone-based
      ecological momentary assessment (EMA) to measure blood glucose monitoring and
      insulin administration in adolescent Type 1 diabetes, 2) relate EMA to
      traditional self-report and glycemic control, and 3) identify patterns of
      adherence by time of day and over time using EMA. METHOD: Adolescents with Type 1
      diabetes (n = 96) completed baseline measures of cell phone use and adherence.
      Glycemic control (measured by levels of HbA1c) was obtained from medical records.
      A subgroup of adolescents (n = 50) completed 10 days of EMA to assess blood
      glucose monitoring frequency, timing of glucose monitoring, insulin
      administration, and insulin dosing. One third of adolescents were not allowed to
      use their cell phones for diabetes at school. Parental restrictions on cell phone
      use at home were not prevalent. RESULTS: The EMA response rate (59%) remained
      stable over the 10-day calling period. Morning time was associated with worse
      monitoring and insulin administration, accounting for 59-74% of missed self-care
      tasks. EMA-reported missed glucose checks and missed insulin doses were
      correlated to traditional self-report data, but not to HbA1c levels. Trajectory
      analyses identified two subgroups: one with consistently adequate adherence, and
      one with more variable, and worse, adherence. The latter adherence style showed
      worse glycemic control. CONCLUSION: Mobile phones provide a feasible method to
      measure glucose monitoring and insulin administration in adolescents, given a
      limited assessment duration. The method provided novel insights regarding
      patterns of adherence and should be explored in clinical settings for targeting
      or tailoring interventions.

PMID- 21967663
TI  - Prestress strengthens the shell of Norwalk virus nanoparticles.
AB  - We investigated the influence of the protruding domain of Norwalk virus-like
      particles (NVLP) on its overall structural and mechanical stability. Deletion of
      the protruding domain yields smooth mutant particles and our AFM nanoindentation
      measurements show a surprisingly altered indentation response of these particles.
      Notably, the brittle behavior of the NVLP as compared to the plastic behavior of
      the mutant reveals that the protruding domain drastically changes the capsid's
      material properties. We conclude that the protruding domain introduces prestress,
      thereby increasing the stiffness of the NVLP and effectively stabilizing the
      viral nanoparticles. Our results exemplify the variety of methods that nature has
      explored to improve the mechanical properties of viral capsids, which in turn
      provides new insights for developing rationally designed, self-assembled
      nanodevices.

PMID- 21967664
TI  - Vaginal progesterone after tocolytic therapy in threatened preterm labor.
AB  - OBJECTIVE: The aim of this study was retrospective evaluation of progesterone
      efficacy in pregnant patients with preterm uterine contractions. MATERIAL: 190
      women hospitalized at 1st Department of Obstetrics and Gynecology, Medical
      University of Warsaw, in 2007-2010, with symptoms of threatened preterm labor
      were enrolled in the study. 94 women were treated with tocolytics and steroids
      (control group), while 96 women received additionally 200 mg of progesterone
      vaginally until delivery or 34th weeks of gestation (progesterone group).
      RESULTS: The mean gestational age at admission was 27 weeks in progesterone group
      and 28 weeks in control group. Cervical length was similar in both groups. There
      were no significant differences in week of delivery between groups, but the
      progesterone group had significant increase in prolongation of pregnancy (7.6
      versus 6.3 weeks, p = 0.039). Vaginal progesterone was associated with reduction
      of delivery before 34 weeks (9.8% versus 35.3%; p = 0.002) and neonatal birth
      weight <1500 g (3.2% versus 20.6%; p = 0.011) only in patients presenting with
      uterine contractions after 27 weeks. CONCLUSION: The administration of vaginal
      progesterone after tocolysis in threatened preterm labor is associated with
      prolongation of pregnancy. The reduction of deliveries before 34 weeks was
      observed in patients presenting with contractions after 27 weeks gestation.

PMID- 21967665
TI  - Exploring the effect of side-chain substitutions upon the secondary structure
      preferences of beta-peptides.
AB  - The ability to design well-folding beta-peptides with a specific biological
      activity requires detailed insight into the relationship between the beta-amino
      acid sequence and the dominant three-dimensional structure of such a peptide. To
      this end, secondary structure preferences of two sets of 16 beta-peptides were
      investigated by means of one-step perturbation using molecular dynamics (MD)
      simulations. For each set of peptides, two reference-state simulations and one
      perturbed-state simulation were carried out to predict the secondary structure
      preferences for the other 15 peptides. The results show that the substitution of
      a methyl group in the third or fourth residue stabilizes the left-handed 3(14)
      helix over the right-handed 2.7(10/12)-helix for the set of hexapeptides A; for
      the set of heptapeptides B, having methyl substitutions at both beta- and alpha
      carbon positions of the fourth or fifth residue stabilizes the left-handed 3(14)
      helix over the right-handed 2.5(12)-helix. Not only the side-chain substitution
      pattern but also the side-chain composition affects the relative stability of
      different secondary structures. The approach described here may be of use in
      peptide design with an eye to obtaining peptides with particular folds and
      biological activities.

PMID- 21967666
TI  - Assembly and photonic properties of superparamagnetic colloids in complex
      magnetic fields.
AB  - Interparticle magnetic dipole force has been found to drive the formation of
      dynamic superparamagnetic colloidal particle chains that can lead to the creation
      of photonic nanostructures with rapidly and reversibly tunable structural colors
      in the visible and near-infrared spectrum. Although most studies on magnetic
      assembly utilize simple permanent magnets or electromagnets, magnetic fields, in
      principle, can be more complex, allowing the localized modulation of assembly and
      subsequent creation of complex superstructures. To explore the potential
      applications of a magnetically tunable photonic system, we study the assembly of
      magnetic colloidal particles in the complex magnetic field produced by a nonideal
      linear Halbach array. We demonstrate that a horizontal magnetic field sandwiched
      between two vertical fields would allow one to change the orientation of the
      particle chains, producing a high contrast in color patterns. A phase transition
      of Fe(3)O(4)@SiO(2) particles from linear particle chains to three-dimensional
      crystals is found to be determined by the interplay of the magnetic dipole force
      and packing force, as well as the strong electrostatic force. While a color
      pattern with tunable structures and diffractions can be instantly created when
      the particles are assembled in the form of linear chains in the regions with
      vertical fields, the large field gradient in the horizontal orientation may
      destabilize the chain structures and produces a pattern of 3D crystals that
      compliments that of initial chain assemblies. Our study not only demonstrates the
      great potential of magnetically responsive photonic structures in the visual
      graphic applications such as signage and security documents but also points out
      the potential challenge in pattern stability when the particle assemblies are
      subjected to complex magnetic fields that often involve large field gradients.

PMID- 21967667
TI  - Modeling invasion of metastasizing cancer cells to bone marrow utilizing
      ecological principles.
AB  - BACKGROUND: The invasion of a new species into an established ecosystem can be
      directly compared to the steps involved in cancer metastasis. Cancer must grow in
      a primary site, extravasate and survive in the circulation to then intravasate
      into target organ (invasive species survival in transport). Cancer cells often
      lay dormant at their metastatic site for a long period of time (lag period for
      invasive species) before proliferating (invasive spread). Proliferation in the
      new site has an impact on the target organ microenvironment (ecological impact)
      and eventually the human host (biosphere impact). RESULTS: Tilman has described
      mathematical equations for the competition between invasive species in a
      structured habitat. These equations were adapted to study the invasion of cancer
      cells into the bone marrow microenvironment as a structured habitat. A large
      proportion of solid tumor metastases are bone metastases, known to usurp
      hematopoietic stem cells (HSC) homing pathways to establish footholds in the bone
      marrow. This required accounting for the fact that this is the natural home of
      hematopoietic stem cells and that they already occupy this structured space. The
      adapted Tilman model of invasion dynamics is especially valuable for modeling the
      lag period or dormancy of cancer cells. CONCLUSIONS: The Tilman equations for
      modeling the invasion of two species into a defined space have been modified to
      study the invasion of cancer cells into the bone marrow microenvironment. These
      modified equations allow a more flexible way to model the space competition
      between the two cell species. The ability to model initial density, metastatic
      seeding into the bone marrow and growth once the cells are present, and movement
      of cells out of the bone marrow niche and apoptosis of cells are all aspects of
      the adapted equations. These equations are currently being applied to clinical
      data sets for verification and further refinement of the models.

PMID- 21967668
TI  - Selective inhibition of jasmonic acid accumulation by a small alpha, beta
      unsaturated carbonyl and phenidone reveals different modes of octadecanoid
      signalling activation in response to insect elicitors and green leaf volatiles in
      Zea mays.
AB  - BACKGROUND: Plants often release a complex blend of volatile organic compounds
      (VOC) in response to insect herbivore damage. Among those blends of VOC green
      leaf volatiles (GLV) have been demonstrated to function as defence signals
      between plants, thereby providing protection against impending herbivory. A
      problem in understanding the mode of action of these 6-carbon aldehydes,
      alcohols, and esters is caused by their structural diversity. Besides different
      degrees of oxidation, E-2- as well as Z-3-configured isomers are often released.
      This study was therefore initiated to determine the structural requirement
      necessary to exhibit biological activity measured as jasmonic acid (JA)
      accumulation in Zea mays seedlings. FINDINGS: The structure/function analysis of
      green leaf volatiles and related compounds revealed that an olefinic bond in
      position 2 or 3 and a size of 6-8 carbons is required for biological activity in
      maize. Also, it was found that the presence of an alpha, beta-unsaturated
      carbonyl is not a prerequisite for activity. However, by treating plants first
      with volatile acrolein it was discovered that this smallest alpha, beta
      unsaturated carbonyl inhibits JA accumulation in response to insect elicitor
      treatment, but not after GLV exposure. This selective inhibitory effect was also
      found for phenidone, an inhibitor of lipoxygenases. These findings led to the
      discovery of a pool of protein-associated 12-oxo-phytodienoic acid, a
      biosynthetic precursor of JA, which appeared to be rapidly converted into JA upon
      exposure to GLV. CONCLUSIONS: The structure/function analysis of GLV demonstrates
      a high degree of correlation between the compounds released by wounded plants in
      nature and their biological activity. The selective inhibitory effects of
      acrolein and phenidone on insect elicitor- and GLV-induced JA accumulation in
      maize led to the discovery of a pool of protein-associated precursor, which is
      rapidly activated and transformed to JA after exposure to GLV. This novel
      mechanism for JA accumulation sheds new light on the biosynthetic variability of
      the octadecanoid signalling pathway and explains the observed differences in the
      response of maize seedling to inhibitors of JA accumulation.

PMID- 21967669
TI  - Visual diagnosis: Enucleation status post gunshot wound to the head: A visual
      diagnosis/case report.
AB  - We present the case of a patient who attempted to commit suicide via a gunshot
      to the head. However, instead of ending his life, he destroyed both of his eyes.
      Computed tomography scans are shown.

PMID- 21967670
TI  - Health consequences of female genital mutilation/cutting in the Gambia, evidence
      into action.
AB  - BACKGROUND: Female Genital Mutilation/Cutting (FGM/C) is a harmful traditional
      practice with severe health complications, deeply rooted in many Sub-Saharan
      African countries. In The Gambia, the prevalence of FGM/C is 78.3% in women aged
      between 15 and 49 years. The objective of this study is to perform a first
      evaluation of the magnitude of the health consequences of FGM/C in The Gambia.
      METHODS: Data were collected on types of FGM/C and health consequences of each
      type of FGM/C from 871 female patients who consulted for any problem requiring a
      medical gynaecologic examination and who had undergone FGM/C in The Gambia.
      RESULTS: The prevalence of patients with different types of FGM/C were: type I,
      66.2%; type II, 26.3%; and type III, 7.5%. Complications due to FGM/C were found
      in 299 of the 871 patients (34.3%). Even type I, the form of FGM/C of least
      anatomical extent, presented complications in 1 of 5 girls and women examined.
      CONCLUSION: This study shows that FGM/C is still practiced in all the six regions
      of The Gambia, the most common form being type I, followed by type II. All forms
      of FGM/C, including type I, produce significantly high percentages of
      complications, especially infections.

PMID- 21967671
TI  - A biorefinery for mobility?
AB  - Biofuels are considered as a carbon neutral alternative to hydrocarbons in the
      transport sector and this approach has triggered concerns about the impact the
      production of biofuels might have on land usage. Another option that might also
      lead to reduced emissions in the transport sector is electricity based on
      renewable energy sources such as biomass. Below, we assess the benefits and
      drawbacks of the joint production of ethanol and electricity in a sugar cane
      based refinery, and the use of both energy forms in privately owned automobiles.
      In this analysis, we have considered technology for energy production that is
      currently available and cost competitive. The results show that the amount of
      land that is required to power our current automobile use needs is less than what
      is typically stated. According to our results that are based on 2010 values, 2
      million ha of land are sufficient to power the Brazilian automobile fleet, 25
      million ha are enough to satisfy the needs of the U.S. fleet, and 67 million ha
      are sufficient to cover the global autofuel requirements. When minor efficiency
      gains are considered, 19 million ha will be enough to satisfy the fuel needs of
      the U.S. fleet in 2030, whereas land required to supply the Brazilian and global
      fleet remain basically unchanged. Our analysis shows that the harvested energy
      density of sugar cane is 306 GJ/ha/yr, which is 1.7 times the value usually
      reported in the literature for biofuels. As a result, taking advantage of the
      primary energy potential of sugar cane, only 4% of the world's available cropland
      area would be sufficient to produce fuels that would power the global car fleet.

PMID- 21967672
TI  - Phosphorylation of extracellular matrix tenascin-X detected by differential mass
      tagging followed by nanoLC-MALDI-TOF/TOF-MS/MS using ProteinPilot software.
AB  - Reversible protein phosphorylation represents a major mechanism of signal
      transduction in a variety of cellular functions. An understanding of proteome
      wide phosphorylation dynamics is important to obtain an overview of the whole
      signal transduction network. However, a systematic analysis for differentially
      expressed phosphoproteins under serum-stimulated response is lacking. Here, an
      easy and fast approach for the identification of differentially expressed
      phosphoproteins was used. After enrichment of phosphoproteins from serum
      stimulated cell lysates by immobilized metal affinity chromatography, a
      quantitative proteomic approach with isobaric tag for absolute and relative
      quantitation labeling in combination with nanoLC-MALDI-TOF/TOF-MS/MS followed by
      ProteinPilot analysis was used. Consequently, 506 differentially expressed
      phosphoproteins were identified. Among them, 22 proteins that had a reproducible
      phosphorylation site at Ser or Thr were identified. Out of these 22
      phosphoproteins, 7 are mainly involved in splicing. Among the 22 proteins, it was
      found that extracellular matrix tenascin-X is phosphorylated, although there is
      little quantitative change by the serum stimulation. MS/MS analysis revealed a
      novel phosphorylation site of tenascin-X, Thr1841, located in the loop region
      between the 10th and 11th fibronectin type III repeats. The phosphorylation of
      tenascin-X would be considered in clarifying its function in the future.

PMID- 21967673
TI  - Cerebral infarction in children with sickle cell disease: a concise overview.
AB  - Cerebral infarction is a common complication in sickle cell disease. Both overt
      and silent infarcts evident on neuroimaging have been described. In this article
      we overview the current knowledge of cerebral infarction in this patient
      population and discuss recent updates on the role of preventive intervention.

PMID- 21967674
TI  - Do statins have a role in reduction/prevention of post-PCI restenosis?
AB  - The pathophysiology of post-PCI restenosis involves neointimal formation that
      consists of three phases: thrombosis (within 24 h), recruitment (3-8 days), and
      proliferation, which starts on day 8 of PCI. Various factors suggested to be
      predictors/risks for restenosis include C-reactive protein (CRP), inflammatory
      mediators (cytokines and adhesion molecules), oxygen radicals, advanced glycation
      end products (AGEs) and their receptors (RAGE), and soluble RAGE (sRAGE). The
      earlier noted factors produce thrombogenesis, vascular smooth muscle cell
      proliferation, and extracellular matrix formation. Statins have pleiotropic
      effects. Besides lowering serum cholesterol, they have various other biological
      effects including antiinflammatory, antithrombotic, CRP-lowering, antioxidant,
      antimitotic, and inhibition of smooth muscle cell proliferation. They inhibit
      matrix metalloproteinase and cyclooxygenase-2, lower AGEs, decrease expression of
      RAGE and increase levels of serum sRAGE. They also increase the synthesis of
      nitric oxide (NO) by increasing endothelial NO synthase expression and activity.
      Preprocedural statin therapy is known to reduce peri- and post-PCI myonecrosis
      and reduce the need for repeat revascularization. There is evidence that statin
      eluting stents inhibit in-stent restenosis in animal models. It is concluded that
      because of the above attributes of statins, they are suitable candidates for
      reduction of post-PCI restenosis and post-PCI myonecrosis. The future directions
      for the use of statins in reduction of post-PCI restenosis and myonecrosis have
      been discussed.

PMID- 21967675
TI  - Development of the coordination between posture and manual control.
AB  - Studies have suggested that proper postural control is essential for the
      development of reaching. However, little research has examined the development of
      the coordination between posture and manual control throughout childhood. We
      investigated the coordination between posture and manual control in children (7-
      and 10-year-olds) and adults during a precision fitting task as task constraints
      became more difficult. Participants fit a block through an opening as arm
      kinematics, trunk kinematics, and center of pressure data were collected. During
      the fitting task, the precision, postural, and visual constraints of the task
      were manipulated. Young children adopted a strategy where they first move their
      trunk toward the opening and then stabilize their trunk (freeze degrees of
      freedom) as the precision manual task is being performed. In contrast, adults and
      older children make compensatory trunk movements as the task is being performed.
      The 10-year-olds were similar to adults under the less constrained task
      conditions, but they resembled the 7-year-olds under the more challenging tasks.
      The ability to either suppress or allow postural fluctuations based on the
      constraints of a suprapostural task begins to develop at around 10 years of age.
      This ability, once developed, allows children to learn specific segmental
      movements required to complete a task within an environmental context.

PMID- 21967676
TI  - Cultural differences in the development of cognitive shifting: East-West
      comparison.
AB  - Prior research has documented that Japanese children's performance on the
      Dimensional Change Card Sorting (DCCS) task can be influenced by their
      observation of another person completing the task, which is referred to as social
      transmission of disinhibition. The current study explored whether Canadian
      children would also show a social transmission of disinhibition and whether their
      performance would be comparable to that of Japanese children. In this study, 3-
      and 4-year-olds in Canada and Japan were given both the standard version and
      social version of the DCCS. Results indicated that Canadian children displayed
      the social transmission of disinhibition, but their effects were significantly
      weaker than those with Japanese children. On the other hand, performance on the
      standard DCCS was comparable between children in the two countries. We discuss
      the results in terms of cultural differences in the relationship between self and
      other.

PMID- 21967678
TI  - How women who have experienced one or more miscarriages manage their feelings and
      emotions when they become pregnant again - a qualitative interview study.
AB  - AIM: The aim of this study was to investigate how women who have experienced one
      or more miscarriages manage their feelings when they become pregnant again.
      METHOD: Individual qualitative interviews were conducted with 16 women who were
      pregnant again after experiencing one or more miscarriages. The interviews were
      analysed using qualitative content analysis with an inductive approach. RESULTS:
      The analysis of the material ended up in five categories: distancing herself from
      her pregnancy, focusing on her pregnancy symptoms, searching for confirming
      information, asking for ultrasound examination and asking for professional and
      social support. Because of their past experience with miscarriage, it could be
      painful to have another pregnancy terminate in disappointment. Therefore, the
      women manage their feelings by distancing themselves from their pregnancies.
      Simultaneously, they are managing their emotions by seeking affirmation that
      their current pregnancy is normal. CONCLUSION: Generally speaking, women manage
      their emotions by themselves. They feel isolated with their worries and concerns,
      and they are in need of the support provided from their intimate circle of
      friends and family as well as from the staff of the maternity health care ward.
      Unfortunately, the women do not feel that they get the support they need from the
      staff, instead they have to rely on their friends, family and partners to help
      them manage their emotions.

PMID- 21967677
TI  - CT angiography predicts use of tertiary interventional services in acute ischemic
      stroke patients.
AB  - BACKGROUND: Patients with acute stroke are often transferred to tertiary care
      centers for advanced interventional services. We hypothesized that the presence
      of a proximal cerebral artery occlusion on CT angiography (CTA) is an independent
      predictor of the use of these services. METHODS: We performed a historical cohort
      study of consecutive ischemic stroke patients presenting within 24 h of symptom
      onset to an academic emergency department who underwent emergent CTA. Use of
      tertiary care interventions including intra-arterial (IA) thrombolysis,
      mechanical clot retrieval, and neurosurgery were captured. RESULTS: During the
      study period, 207/290 (71%) of patients with acute ischemic stroke underwent
      emergent CTA. Of the patients, 74/207 (36%) showed evidence of a proximal
      cerebral artery occlusion, and 22/207 (11%) underwent an interventional
      procedure. Those with proximal occlusions were more likely to receive a
      neurointervention (26% vs. 2%, p < 0.001). They were more likely to undergo IA
      thrombolysis (9% vs. 0%, p = 0.001) or a mechanical intervention (19% vs. 0%, p <
      0.0001), but not more likely to undergo neurosurgery (5% vs. 2%, p = 0.2). After
      controlling for the initial NIH stroke scale (NIHSS) score, proximal occlusion
      remained an independent predictor of the use of neurointerventional services (OR
      8.5, 95% CI 2.2-33). Evidence of proximal occlusion on CTA predicted use of
      neurointervention with sensitivity of 82% (95% CI 59-94%), specificity of 71%
      (95% CI 64%-77%), positive predictive value (PPV) of 25% (95% CI 16%-37%), and
      negative predictive value (NPV) of 97% (95% CI 92%-99%). CONCLUSION: Proximal
      cerebral artery occlusion on CTA predicts the need for advanced
      neurointerventional services.

PMID- 21967679
TI  - Characterization of collagen thin films for von Willebrand factor binding and
      platelet adhesion.
AB  - Von Willebrand factor (VWF) binding and platelet adhesion to subendothelial
      collagens are initial events in thrombus formation at sites of vascular injury.
      These events are often studied in vitro using flow assays designed to mimic
      vascular hemodynamics. Flow assays commonly employ collagen-functionalized
      substrates, but a lack of standardized methods of surface ligation limits their
      widespread use as a clinical diagnostic. Here, we report the use of collagen thin
      films (CTF) in flow assays. Thin films were grown on hydrophobic substrates from
      type I collagen solutions of increasing concentration (10, 100, and 1000 MUg/mL).
      We found that the corresponding increase in fiber surface area determined the
      amount of VWF binding and platelet adhesion. The association rate constant (k(a))
      of plasma VWF binding at a wall shear stress of 45 dyn/cm(2) was 0.3 * 10(5), 1.8
      * 10(5), and 1.6 * 10(5) M(-1) s(-1) for CTF grown from 10, 100, and 1000 MUg/mL
      solutions, respectively. We observed a 5-fold increase in VWF binding capacity
      with each 10-fold increase in collagen solution concentration. The association
      rates of Ser1731Thr and His1786Asp VWF mutants with collagen binding deficiencies
      were 9% and 22%, respectively, of wild-type rates. Using microfluidic devices for
      blood flow assays, we observed that CTF supported platelet adhesion at a wall
      shear rate of 1000 s(-1). CTF grown from 10 and 100 MUg/mL solutions had variable
      levels of platelet surface coverage between multiple normal donors. However, CTF
      substrates grown from 1000 MUg/mL solutions had reproducible surface coverage
      levels (74 +/- 17%) between normal donors, and there was significantly diminished
      surface coverage from two type 1 von Willebrand disease patients (8.0% and 24%).
      These results demonstrate that collagen thin films are homogeneous and
      reproducible substrates that can measure dysfunctions in VWF binding and platelet
      adhesion under flow in a clinical microfluidic assay format.

PMID- 21967680
TI  - Validation of a self-report version of the diabetes self-management profile.
AB  - Inadequate treatment adherence impedes achievement of glycemic control targets in
      type 1 diabetes (T1D). Valid and reliable measurement of treatment adherence is a
      prerequisite to rigorous evaluation of pertinent interventions. The diabetes self
      management profile (DSMP), a structured interview measure of T1D adherence, is
      valid and reliable but it requires trained interviewers, it is labor intensive to
      administer and it is burdensome for research participants. We adapted the DSMP
      interview to create the DSMP-self-report questionnaire (DSMP-SR) for completion
      by parents and youth >=11 yr old. The DSMP-SR was obtained during a cross
      sectional study of 151 youth within the age range of 8 to <18 yr with T1D [male,
      50.7%; racial minorities, 23%; mean age, 13.9 yr; T1D duration, 5.5 yr;
      hemoglobin A1c (HbA1c), 8.7%] and a parent of each. Parents and youth >=11 yr old
      completed the DSMP-SR independently. The DSMP-SR had sound internal consistency
      (Cronbach's alpha: youth, 0.82; parent, 0.80), and parent-youth agreement, (r =
      0.60, p < 0.001) and significant associations with HbA1c (r = -0.35 for youth and
      -0.46 for parents, p < 0.001), PedsQL quality of life scale (youth: r = -0.41, p
      < 0.001; parent: r = -0.40, p < 0.001) and, for parents but not youth, the
      Revised Diabetes Family Conflict Scale (r = -0.47, p < 0.001). Higher DSMP-SR
      scores were associated with lower HbA1c, better quality of life, and less family
      conflict. The DSMP-SR has similar psychometric properties to those reported
      elsewhere for the DSMP, yielding a convenient measure of T1D adherence.

PMID- 21967681
TI  - A case of squamous cell carcinoma arising from a suprapubic cystostomy tract.
AB  - BACKGROUND: Patients with spinal cord injury and a chronic indwelling urinary
      catheter are known to have an increased risk of bladder malignancy. However,
      squamous cell carcinoma (SCC) of the epidermis around a suprapubic cystostomy is
      relatively rare. Here, we report a case of lower abdominal SCC arising from the
      suprapubic cystostomy tract. CASE PRESENTATION: A 58-year-old man with a complete
      spinal cord injury was referred to our hospital with a chief complaint of an
      abdominal mass. Abdominal enhanced computed tomography (CT) showed a 7-cm mass
      surrounding the suprapubic cystostomy and bilateral inguinal and para-aortic
      lymph nodes metastasis. Histopathological examination of percutaneous biopsy
      specimens was performed. The diagnosis was stage IV (cT4N1M1) epidermal SCC,
      which was treated with palliative external radiation therapy. CONCLUSION: The SCC
      in this case was thought to arise from mechanical stimulus of the suprapubic
      cystostomy. Physicians and patients should pay careful attention to any signs of
      neoplasms with long-term indwelling catheters, such as skin changes around the
      suprapubic cystostomy site. This case presentation is only the fourth report of
      SCC arising from the suprapubic cystostomy tract in the literature. In cases of
      unresectable tumors and contraindications to chemotherapy, palliative
      radiotherapy may lead to disease remission and symptom relief.

PMID- 21967682
TI  - The effect of an intercalated BSc on subsequent academic performance.
AB  - BACKGROUND: The choice of whether to undertake an intercalated Bachelor of
      Science (BSc) degree is one of the most important decisions that students must
      make during their time at medical school. An effect on exam performance would
      improve a student's academic ranking, giving them a competitive edge when
      applying for foundation posts. METHODS: Retrospective data analysis of anonymised
      student records. The effects of intercalating on final year exam results,
      Foundation Programme score, application form score (from white-space questions),
      quartile rank score, and success with securing Foundation School of choice were
      assessed using linear and ordered logistic regression models, adjusted for course
      type, year of graduation, graduate status and baseline (Year 1) performance.
      RESULTS: The study included 1158 students, with 54% choosing to do an
      intercalated BSc, and 9.8% opting to do so at an external institution. Doing an
      intercalated BSc was significantly associated with improved outcome in Year 5
      exams (P = 0.004). This was irrespective of the year students chose to
      intercalate, with no significant difference between those that intercalated after
      years 2, 3 and 4 (p = 0.3096). There were also higher foundation application
      scores (P < 0.0001), academic quartile scores (P = 0.0003) and resultant overall
      foundation scores (P < 0.0001) in intercalated students. These students also had
      improved success with securing their first choice Foundation School (p = 0.0220).
      Participants who remained at the institution to intercalate in general performed
      better than those that opted to intercalate elsewhere. CONCLUSIONS: Doing an
      intercalated BSc leads to an improvement in subsequent exam results and develops
      the skills necessary to produce a strong foundation programme application. It
      also leads to greater success with securing preferred Foundation School posts in
      students. Differences between internally- and externally-intercalating students
      may be due to varying course structures or greater challenge in adjusting to a
      new study environment.

PMID- 21967683
TI  - Effect on hepatonephric organs, serum metabolites and oxidative stress in post
      weaning piglets fed purified zearalenone-contaminated diets with or without
      Calibrin-Z.
AB  - The objectives of this study were to investigate the toxicity of zearalenone
      (ZEA) on hepatonephric organs, serum metabolites and oxidative stress of piglets
      and to evaluate the efficacy of Calibrin-Z (CAZ) in preventing ZEA-induced
      adverse effects. The experiment was conducted for 22 days using 36 piglets weaned
      at 21 days of age (Landrace * Yorkshire * Duroc, 18 females and 18 males; 8.84 +/
      0.21 kg average body weight). Piglets of each gender were randomly allocated to
      the following six dietary treatments: (i) Control (basal diet only); (ii) Control
      + 1 g/kg CAZ; (iii) Control + 1 mg/kg ZEA; (iv) Control + 1 mg/kg ZEA + 1 g/kg
      CAZ; (v) Control + 1 mg/kg ZEA + 2 g/kg CAZ; (vi) Control + 1 mg/kg ZEA + 4 g/kg
      CAZ. Piglets were housed and fed individually for the entire experimental period.
      Blood samples were taken, and piglets were killed at the end of the experiment to
      obtain organs for physiological assessment. Results showed that piglets fed the
      ZEA-contaminated diet had increased (p < 0.05) activities of aspartate
      aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma
      glutamyltransferase (GGT), creatine kinase and cholinesterase, concentrations of
      urea, and creatinine in serum, and malondialdehyde (MDA) in serum and liver. Pigs
      fed the ZEA-only diet also showed reductions in serum (p < 0.05) globulin,
      triglycerides and high-density lipoproteins (HDL), and reductions in total
      superoxide dismutase (TSOD) and glutathione peroxidase (GSHPx) activity in both
      serum and liver. Supplementation of CAZ at the dosages of 1-4 g/kg to the diet
      containing 1.05 mg/kg ZEA linearly increased (p < 0.05) concentrations of
      triglycerides and HDL in serum, activity of TSOD and GSHPx in serum and liver,
      but linearly reduced (p < 0.05) all tested serum enzymes and lowered (p < 0.05)
      the elevated concentrations of urea, and creatinine in serum, and MDA in serum
      and liver caused by dietary ZEA. Piglets fed the ZEA-contaminated diet showed
      increased (p < 0.05) relative weight of liver and kidney compared with the
      control, whereas only numerical improvement on relative weight of liver and
      kidney was observed with simultaneous addition of CAZ at 4 g/kg diet and ZEA.
      However, feeding the diet with CAZ alone at 1 g/kg had no impact on any of the
      measured parameters when compared to the control. It is suggested that feeding
      ZEA at 1.05 mg/kg exerted a deleterious effect on piglets, which was totally or
      partly ameliorated by dietary supplementation of CAZ at concentrations between 1
      and 4 g/kg diet.

PMID- 21967685
TI  - Chronic cough and tachycardia-induced cardiomyopathy in a patient with idiopathic
      frequent, monomorphic premature ventricular contractions.
AB  - A 70-year-old woman presented with a 1-year history of dry cough. Extensive work
      up ruled out common causes of chronic cough. She was found to have very frequent,
      monomorphic premature ventricular contractions (PVCs) and mild-to-moderate left
      ventricular systolic dysfunction. Propafenone 450 mg/day resulted in complete
      resolution of her cough and disappearance of PVCs within 24 hours of initiation.
      One month after the initiation of propafenone therapy, left ventricular ejection
      fraction normalized and her chronic cough resolved completely.

PMID- 21967684
TI  - Analysis of native biological surfaces using a 100 kV massive gold cluster
      source.
AB  - In the present work, the advantages of a new, 100 kV platform equipped with a
      massive gold cluster source for the analysis of native biological surfaces are
      shown. Inspection of the molecular ion emission as a function of projectile size
      demonstrates a secondary ion yield increase of ~100* for 520 keV Au(400)(4+) as
      compared to 130 keV Au(3)(1+) and 43 keV C(60). In particular, yields of tens of
      percent of molecular ions per projectile impact for the most abundant components
      can be observed with the 520 keV Au(400)(4+) probe. A comparison between 520 keV
      Au(400)(4+) time-of-flight-secondary ion mass spectrometry (TOF-SIMS) and matrix
      assisted laser desorption ionization-mass spectrometry (MALDI-MS) data showed a
      similar pattern and similar relative intensities of lipid components across a rat
      brain sagittal section. The abundant secondary ion yield of analyte-specific ions
      makes 520 keV Au(400)(4+) projectiles an attractive probe for submicrometer
      molecular mapping of native surfaces.

PMID- 21967686
TI  - Clusterwise simultaneous component analysis for analyzing structural differences
      in multivariate multiblock data.
AB  - Many studies yield multivariate multiblock data, that is, multiple data blocks
      that all involve the same set of variables (e.g., the scores of different groups
      of subjects on the same set of variables). The question then rises whether the
      same processes underlie the different data blocks. To explore the structure of
      such multivariate multiblock data, component analysis can be very useful.
      Specifically, 2 approaches are often applied: principal component analysis (PCA)
      on each data block separately and different variants of simultaneous component
      analysis (SCA) on all data blocks simultaneously. The PCA approach yields a
      different loading matrix for each data block and is thus not useful for
      discovering structural similarities. The SCA approach may fail to yield insight
      into structural differences, since the obtained loading matrix is identical for
      all data blocks. We introduce a new generic modeling strategy, called clusterwise
      SCA, that comprises the separate PCA approach and SCA as special cases. The key
      idea behind clusterwise SCA is that the data blocks form a few clusters, where
      data blocks that belong to the same cluster are modeled with SCA and thus have
      the same structure, and different clusters have different underlying structures.
      In this article, we use the SCA variant that imposes equal average cross-products
      constraints (ECP). An algorithm for fitting clusterwise SCA-ECP solutions is
      proposed and evaluated in a simulation study. Finally, the usefulness of
      clusterwise SCA is illustrated by empirical examples from eating disorder
      research and social psychology.

PMID- 21967687
TI  - Protective effect of Polyalthia longifolia var. pendula leaves on ethanol and
      ethanol/HCl induced ulcer in rats and its antimicrobial potency.
AB  - OBJECTIVE: To explore antiulcer and antimicrobial properties of methanolic
      extract of Polyalthia longifolia var. pendula. METHODS: Gastroprotective
      potential of Polyalthia longifolia was studied on ethanol and ethanol/HCl induced
      ulcers at 2 different doses (270 and 540 mg/kg/body weight). Antimicrobial
      efficacy of Polyalthia longifolia (25 mg/mL) was also studied against six gram
      positive, seven gram negative bacteria and five fungi by agar well diffusion
      method. Minimum inhibitory concentration was determined by agar well diffusion
      method in two fold serial dilution, in the range of 97-25,000 MUg/mL. RESULTS:
      The reduction of ulcer index in Polyalthia longifolia treated animals was found
      to be statistically significant with respect to control animals. The Polyalthia
      longifolia exhibited ulcer protection activity in dose dependent manner and was
      also better than the standard. In antimicrobial activity, gram positive bacteria
      were more susceptible to Polyalthia longifolia than gram negative bacteria and
      fungal strains. CONCLUSIONS: Results obtained confirm the antiulcer and
      antimicrobial potential of the Polyalthia longifolia.

PMID- 21967688
TI  - Floral extract of Tecoma stans: a potent inhibitor of gentamicin-induced
      nephrotoxicity in vivo.
AB  - OBJECTIVE: To highlight the nephroprotective activity of ethyl acetate extract of
      dried flowers of Tecoma stans for its protective effects on gentamicin-induced
      nephrotoxicity in albino rats. METHODS: For studying acute toxicity study, single
      oral dose of 5,000 mg ethyl acetate floral extract/kg body weight was
      administered to albino rats (five females, five males). Nephrotoxicity was
      induced in albino rats by intraperitoneal administration of gentamicin 80
      mg/kg/day for eight days. Effect of concurrent administration of ethyl acetate
      floral extract of Tecoma stans at a dose of 100, 200 and 300 mg/kg/day given by
      oral route was determined using serum creatinine, serum uric acid, blood urea
      nitrogen and serum urea as indicators of kidney damage. The study groups
      contained six rats in each group. As nephrotoxicity of gentamicin is known to
      involve induction of oxidative stress, in vitro antioxidant activity and free
      radical-scavenging activity of this extract was also evaluated. RESULTS: For
      acute toxicity testing both female and male rats administered with the extract at
      a dose of 5,000 mg/kg. The results showed no toxicity in terms of general
      behavior change, mortality, or change in gross appearance of internal organs
      (LD(50) > 5 000 mg/kg). It was observed that the ethyl acetate floral extract of
      Tecoma stans significantly protected rat kidneys from gentamicin-induced
      histopathological changes. Gentamicin-induced glomerular congestion, peritubular
      and blood vessel congestion, epithelial desquamation, accumulation of
      inflammatory cells and necrosis of the kidney cells were found to be reduced in
      the groups receiving the ethyl acetate floral extract of Tecoma stans along with
      gentamicin in a dose dependent manner. The floral extract also reduced the
      gentamicin-induced increase in serum creatinine, serum uric acid, blood urea
      nitrogen and serum urea levels (P >0.01). CONCLUSIONS: The present study
      indicates a very important role of reactive oxygen species (ROS) and the relation
      to renal dysfunction and point to the therapeutic potential of Tecoma stans in
      gentamicin induced nephrotoxicity.

PMID- 21967689
TI  - General anesthesia-associated DNA damage in peripheral blood mononuclear cells of
      surgical patients.
AB  - OBJECTIVE: To evaluate retrospectively the effect of general anesthesia on DNA
      damage in the blood mononuclear cells (PBMCs) of surgical patients in order to
      provide evidence for a better nursing care during the procedure. METHODS:
      Clinical charts of 76 patients who underwent operation under general anesthesia
      and 76 healthy control subjects with documented results of DNA damage extent in
      PBMCs from the single-cell gel electrophoresis (SCGE) or comet assay and serum
      contents of superoxide dismutase (SOD) and malondialdehyde (MDA) from biochemical
      analyses were reviewed. The percentage of comet PBMCs and tail DNA and serum
      contents of SOD and MAD were analyzed by student t-test. RESULTS: Compared with
      healthy control subjects, generally anesthetized surgical patients had
      significantly higher % comet PBMCs and % tail DNA (P <0.05) and significantly
      lower serum concentrations of SOD (P<0.05) and significantly higher serum
      concentrations of MAD (P<0.05). Compared with levels before general anesthesia in
      surgical patients, % comet PBMCs, % tail DNA, and serum levels of MAD were
      significantly higher (P<0.05 or 0.01, and serum levels of SOD were significantly
      lower (P<0.05, after general anesthesia. CONCLUSIONS: General anesthesia during
      surgery causes a certain degree of hypoxia and PBMC damage. Particular attention
      should be paid to monitoring and maintenance of blood oxygen saturation in
      patients undergoing surgery under general anesthesia.

PMID- 21967690
TI  - Anti-hyperglycemic activity of leaves extract of Hyptis suaveolens L. Poit in
      streptozotocin induced diabetic rats.
AB  - OBJECTIVE: To evaluate the antihyperglycemic activity of leaves of Hyptis
      suaveolens using streptozotocin model. METHODS: Hyptis suaveolens extract (HSE)
      250 and 500 mg/kg body weight was administered orally to streptozotocin induced
      diabetes, once daily for 21 days. RESULTS: A significant reduction in blood
      glucose was observed in diabetic animals treated with HSE at different doses when
      compared with diabetic rats. Levels of triglyceride, total cholesterol, low
      density lipoprotein, very low density lipoprotein were decreased while
      administering HSE at different doses, compared with their control values in
      diabetic animals. CONCLUSIONS: Our results show that HSE possesses significant
      antihyperglycemic activity which might be attributed to stimulating effects on
      glucose utilization and antioxidant enzyme.

PMID- 21967691
TI  - Inhibitory effect of two Indian medicinal plants on aldose reductase of rat lens
      in vitro.
AB  - OBJECTIVE: To assesse the inhibitory effect of alcoholic extract of two Indian
      medicinal plants namely Ceasalpinia digyna Rottler and, Alangium lamarckii
      Thwaits on aldose reductase (AR) of rat lens. METHODS: Rats lens were enucleated
      through posterior approach and their homogenate was prepared and centrifuged to
      obtain a clear supernatant for the determination of AR activity and protein
      content. RESULTS: The alcoholic extract of Ceasalpinia digyna and Alangium
      lamarckii had a potent inhibitory effect on the lens AR enzyme. The IC(50) values
      of alcoholic extract of the selected plants were calculated and were (46.29+/
      11.17) and (106.00+/-5.11) MUg/mL, respectively. Quercetin was used as a positive
      control and its IC(50) value was (2.95+/-1.53) MUg/mL. CONCLUSIONS: Thus, it is
      concluded that alcoholic extracts of the selected plant exhibit significant
      inhibitory effects on AR in the rat lens in vitro.

PMID- 21967692
TI  - Larvicidal and repellent activity of medicinal plant extracts from Eastern Ghats
      of South India against malaria and filariasis vectors.
AB  - OBJECTIVE: To evaluate the larvicidal and repellent activities of ethyl acetate
      and methanol extracts of Acacia concinna (A. concinna), Cassia siamea (C.
      siamea), Coriandrum sativum (C. sativum),Cuminum cyminum (C. cyminum), Lantana
      camara (L. camara), Nelumbo nucifera (N. nucifera) Phyllanthus amarus (P.
      amarus), Piper nigrum (P. nigrum) and Trachyspermum ammi (T. ammi) against
      Anopheles stephensi (An. stephensi) and Culex quinquefasciatus (Cx.
      quinquefasciatus). METHODS: The larvicidal activity of medicinal plant extracts
      were tested against early fourth-instar larvae of malaria and filariasis vectors.
      The mortality was observed 24 h and 48 h after treatment, data were subjected to
      probit analysis to determine the lethal concentrations (LC(50) and LC(90)) to
      kill 50 and 90 per cent of the treated larvae of the tested species. The
      repellent efficacy was determined against two mosquito species at five
      concentrations (31.25, 62.50, 125.00, 250.00, and 500.00 ppm) under the
      laboratory conditions. RESULTS: All plant extracts showed moderate effects after
      24 h and 48 h of exposure; however, the highest activity was observed after 24 h
      in the leaf methanol extract of N. nucifera, seed ethyl acetate and methanol
      extract of P. nigrum against the larvae of An. stephensi (LC(50) = 34.76, 24.54
      and 30.20 ppm) and against Cx. quinquefasciatus (LC(50) = 37.49, 43.94 and 57.39
      ppm), respectively. The toxic effect of leaf methanol extract of C. siamea, seed
      methanol extract of C. cyminum, leaf ethyl acetate extract of N. nucifera, leaf
      ethyl acetate and methanol extract of P. amarus and seed methanol extract of T.
      ammi were showed 100% mortality against An. stephensi and Cx. quinquefasciatus
      after 48 h exposer. The maximum repellent activity was observed at 500 ppm in
      methanol extracts of N. nucifera, ethyl acetate and methanol extract of P. nigrum
      and methanol extract of T. ammi and the mean complete protection time ranged from
      30 to 150 min with the different extracts tested. CONCLUSIONS: These results
      suggest that the leaf and seed extracts of C. siamea, N. nucifera, P. amarus, P.
      nigrum and T. ammi have the potential to be used as an ideal ecofriendly approach
      for the control of the An. stephensi and Cx. quinquefasciatus.

PMID- 21967693
TI  - Larvicidal and repellent activity of tetradecanoic acid against Aedes aegypti
      (Linn.) and Culex quinquefasciatus (Say.) (Diptera:Culicidae).
AB  - OBJECTIVE: To investigate the larvicidal and repellent efficacy of tetradecanoic
      acid against Aedes aegypti (Ae. aegypti) L. and Culex quinquefasciatus (Cx.
      quinquefasciatus) Say (Diptera: Culicidae). METHODS: Larvicidal efficacy of
      tetradecanoic acid was tested at various concentrations against the early third
      instar larvae of Ae. aegypti and Cx. quinquefasciatus. The repellent activity was
      determined against two mosquito species at three concentrations viz., 1.0,2.5 and
      5.0 ppm under the laboratory conditions. RESULTS: The tetradecanoic acid was
      found to be more effective against Cx. quinquefasciatus than Ae. aegypti larvae.
      The LC(50) values were 14.08 ppm and 25.10 ppm, respectively. Tetradecanoic acid
      showed lesser repellency against Ae. aegypti and Cx. quinquefasciatus. The
      highest repellency was observed in higher concentration of 5.0 mg/cm(2) provided
      100% protection up to 60 and 90 min against Ae. aegypti and Cx. quinquefasciatus
      respectively. CONCLUSIONS: From the results it can be concluded the tetradecanoic
      acid is a potential for controlling Cx. quinquefasciatus and Ae. aegypti
      mosquitoes.

PMID- 21967694
TI  - Efficacy of Limonia acidissima L. (Rutaceae) leaf extract on larval immatures of
      Culex quinquefasciatus Say 1823.
AB  - OBJECTIVE: To investigate the role of leaf extract of Limonia acidissima L.
      (Rutaceae) as a biocontrol agent against the larval form of Culex
      quinquefasciatus, and characterization of bioactive component responsible for
      larvicidal activity. METHODS: Larval mortality of mosquito species was observed
      after 24, 48 and 72 hours of exposure to different concentrations of aqueous
      extract, solvent extract and subsequently bioactive compound. The bioactive
      compound was subjected to IR and GC-MS analysis. RESULTS: Mortality rate at 3%
      concentration of crude extract were highest (90%) amongst all concentrations
      tested and subsequently highest (95%) mortality was achieved in chloroform:
      methanol extract at 100 ppm concentrations. IR and GC-MS analysis of bioactive
      compound revealed the presence of steroid compound which may act as larvicide.
      CONCLUSIONS: The chloroform: methanol extract of mature leaves of Limonia
      acidissima was found to exhibit considerable mosquito larvicidal activity against
      Culex quinquefasciatus.

PMID- 21967695
TI  - In vitro total phenolics, flavonoids contents and antioxidant activity of
      essential oil, various organic extracts from the leaves of tropical medicinal
      plant Tetrastigma from Sabah.
AB  - OBJECTIVE: To detect the in vitro total phenolics, flavonoids contents and
      antioxidant activity of essential oil, various organic extracts from the leaves
      of tropical medicinal plant Tetrastigma from Sabah. METHODS: The dry powder
      leaves of Tetrastigma were extracted with different organic solvent such as
      hexane, ethyl acetate, chloroform, butanol and aqueous methanol. The total
      phenolic and total flavonoids contents of the essential oil and various organic
      extracts such as hexane, ethyl acetate, chloroform, butanol and aqueous ethanol
      were determined by Folin - Ciocalteu method and the assayed antioxidant activity
      was determined in vitro models such as antioxidant capacity by radical scavenging
      activity using alpha, alpha-diphenyl- beta-picrylhydrazyl (DPPH) method. RESULTS:
      The total phenolic contents of the essential oil and different extracts as gallic
      acid equivalents were found to be highest in methanol extract (386.22 mg/g)
      followed by ethyl acetate (190.89 mg/g), chloroform (175.89 mg/g), hexane (173.44
      mg/g), and butanol extract (131.72 mg/g) and the phenolic contents not detected
      in essential oil. The antioxidant capacity of the essential oil and different
      extracts as ascorbic acid standard was in the order of methanol extract > ethyl
      acetate extract >chloroform> butanol > hexane extract also the antioxidant
      activity was not detected in essential oil. CONCLUSIONS: The findings show that
      the extent of antioxidant activity of the essential oil and all extracts are in
      accordance with the amount of phenolics present in that extract. Leaves of
      Tetrastigma being rich in phenolics may provide a good source of antioxidant.

PMID- 21967696
TI  - Pharmacological and biomedical properties of sea anemones Paracondactylis
      indicus, Paracondactylis sinensis, Heteractis magnifica and Stichodactyla haddoni
      from East coast of India.
AB  - OBJECTIVE: To explore the biomedical and pharmacological activity of
      Paracondactylis indicus (P. indicus), Paracondactylis sinensis (P. sinensis),
      Heteractis magnifica (H. magnifica) and Stichodactyla haddoni (S. haddoni).
      METHODS: The live sea anemones were kept inside the glass bowl along with some
      amount of distilled water in an ice container for 15 min. During stress
      condition, nematocysts released from the tentacles were collected and centrifuged
      at 5,000 rpm for 15 min. The supernatant were collected in separate cleaned
      beakers for lyophilisation. RESULTS: The protein content of crude extracts was
      15.2, 28.7, 18.2 and 35.4 MUg/mL. In hemolytic assay, the P. indicus was
      sensitive (16.842 HT/mg) on chicken blood but P. sinensis was less sensitive
      (1.114 HT/mg) on chicken and goat blood. Whereas H. magnifica and S. haddoni
      showed hemolysis (0.879, 0.903 HT/mg and 56.263, 0.451 HT/mg) in chicken and goat
      blood. In antimicrobial assay, the methanol extract of P. indicus showed maximum
      inhibition zone of 9.7 mm against S. typhii and P. sinensis showed 9.8 mm against
      K. pneumonia in methanol and ethanol extracts. Whereas the H. magnifica and S.
      haddoni showed maximum of 10 mm against S. typhii, K. pneumonia in methanol and
      ethanol extracts. CONCLUSIONS: The high toxic sea anemones may also contain some
      biologically active agents which has haemolytic, analgesic and anti-infilamatory
      activity.

PMID- 21967697
TI  - In vitro bioactivity and phytochemical screening of Suaeda maritima (Dumort): a
      mangrove associate from Bhitarkanika, India.
AB  - OBJECTIVE: To investigate the in vitro antioxidant and antimicrobial activities
      along with phytochemical screening of organic and aqueous extracts of leaf and
      stem of Suaeda maritima (Dumort), a mangrove associate from Bhitarkanika of
      Odisha, India. METHODS: Antioxidant activity of the crude extracts was evaluated
      in terms of total antioxidant capacity, total phenol content, ascorbic acid
      content, DPPH radical scavenging, metal chelating, nitric oxide scavenging, and
      reducing power etc. The antimicrobial activity of the plant was determined by
      agar well diffusion method along with MIC and MBC carried out by microdilution
      techniques against 10 gram positive and gram negative human pathogenic bacteria.
      The qualitative and quantative phytochemical screening were carried out by
      standard biochemical assays. RESULTS: Out of the seven antioxidant bioassays,
      both the leaf and stem extracts were found to posses strong antioxidant
      properties of 70 % to 92 % for phenol, total antioxidant capacity, DPPH free
      radical scavenging activity and fairly good ascorbic acid content, metal
      chelating (1.33 %-22.55 %), reducing power (0.01-0.12) and nitric oxide
      scavenging (0.84 %-66.99 %) activities. Out of the four extracts evaluated for
      antimicrobial activity, two leaf extracts such as acetone and ethanol showed
      promising activity against four pathogenic bacteria and one stem methanol
      extracts against one pathogenic bacteria when compared with amoxcycillin as
      standard. The MIC and MBC values of the antimicrobial extracts ranged between 2.5
      to 5.0 mg/mL. Screening of phytochemicals showed presence of carbohydrates,
      protein, tannins, alkaloids and flavonoids in comparatively higher amount than
      other phytochemicals tested. CONCLUSIONS: The present study reveals the presence
      of potential antioxidants and antimicrobial properties in the plant extract which
      could be exploited for pharmaceutical application.

PMID- 21967698
TI  - Phytochemical constituents and antibacterial efficacy of the flowers of
      Peltophorum pterocarpum (DC.) Baker ex Heyne.
AB  - OBJECTIVE: To investigate the preliminary phytochemistry and antibacterial
      activity of the flower extract of Peltophorum pterocarpum . METHODS:
      Phytochemical analysis was done by using the standard methods given by Harbone.
      The methanolic flower extract were tested against Escherichia coli, Klebsiella
      pneumonia, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus cereus,
      Salmonella typhi, Serratia marsecens, Acinetobacter baumannii, Enterobacter sp.,
      Proteus mirabilis, Enterococcus faecalis and Streptococcus pyogenes by the agar
      disc diffusion method. RESULTS: Preliminary phytochemical screening of flower
      extract showed the presence of phenolic compounds, flavonoids, saponins,
      steroids, tannins, xanthoproteins, carboxylic acids, coumarins and carbohydrates.
      The flower extract of Peltophorum pterocarpum showed significant activity against
      four gram positive (Staphylococcus aureus, Bacillus cereus, Enterococcus faecalis
      and Streptococcus pyogenes) and three gram negative bacteria (Proteus mirabilis,
      Acinetobacter baumannii and Serratia marsecens), out of 12 pathogenic bacteria
      studied. CONCLUSIONS: The findings of the present study confirm the presence of
      significant antibacterial activity against human pathogens in the flowers of
      Peltophorum pterocarpum.

PMID- 21967699
TI  - Identification, structure and function of a novel tetraspaninhomologue from
      Spirometra erinaceieuropaei.
AB  - OBJECTIVE: To identify a full length c DNA sequence of a novel tetraspanin (TSP)
      homologue from Spirometra erinaceieuropaei and to predict the structure and
      function of its encoding protein using bioinformatics methods. METHODS: Using the
      NCBI, EMBI, Expasy and other online sites, the open reading frame (ORF),
      conserved domain, physical and chemical parameters, signal peptide, transmembrane
      domain, epitope, topological structures of the protein sequences were predicted.
      And Vector NTI software was used for multiple sequence alignment and phylogenetic
      tree construction. RESULTS: The target sequence was 1132 bp length with a 681
      bpbiggest ORF encoding 226 amino acids protein with typical TSP conserved domain.
      It was confirmed as full length c DNA of TSP16 from Spirometra erinaceieuropaei
      and named as SeTSP16 (GenBank accession number: JF728872). The predicted
      molecular weight and isoelectric point of the deduced protein were 24 750.5 Da
      and 7.88 Da, respectively. Compared with TSP16s from Schistosoma japonicum and
      Schistosoma mansoni, it showed similarity of 59% and 59%, respectively. SeTSP16
      contained four transmembrane domains (TM1-4), intracellular N and C-termini, one
      short small extracellular loop and one large extracellular loop. Four major
      epitopes that were significant different from the corresponding epitope regions
      of TSP16 from Schistosoma mansoni and Schistosoma japonicum were predicted.
      CONCLUSIONS: The full length c DNA sequences of SeTSP16 are identified. It
      encodes a transmembrane protein which might be an ideal diagnosis antigen and
      target molecule for antiparasitic drugs.

PMID- 21967700
TI  - Antihaemolytic and snake venom neutralizing effect of some Indian medicinal
      plants.
AB  - OBJECTIVE: To validate traditional claims of usefulness of the Indian plants in
      management of poisonous snakebite and evaluate the antivenom properties displayed
      by the alcoholic extracts of Andrographis paniculata (A. paniculata), Crateva
      magna (C. magna), Gloriosa superba (G. superba) and Hydrocotyle javanica (H.
      javanica). METHODS: These plants were collected, identified and the extracts were
      prepared by using conventional Soxhlet ethanol extraction technique. The venom
      neutralization activity was accessed in mice (20-25g) and number of mortalities
      was observed against clinically important snake (Naja nigricollis) venom. Present
      study also deals with in vitro membrane stabilizing activity of these plants
      against hyposaline induced human red blood corpuscles (HRBC). RESULTS: Extracts
      of H. javanica and G. superba gave 80 % and 90 % protection to mice treated with
      minimum lethal dose of venom (LD(99)). These two plants showed significant
      neutralization effect against the venoms of Naja nigricollis venom. H. javanica
      and G. superba (25-100 mg/mL) produced significant changes of membrane
      stabilization of human red blood cells (HRBC) exposed to hyposaline-induced
      haemolysis. CONCLUSIONS: We conclude that probably due to presence of various
      phytochemicals plays an important role in the anti-venom potential of these
      Indian medicinal plants against Naja nigricollis venom. The above observations
      confirmed that A. paniculata, C. magna, G. superba and H. javanica plant extracts
      possess potent snake venom neutralizing capacity and could potentially be used as
      an adjuvants for antivenin therapy in case of snakebite envenomation, especially
      against the local effects of cobra venoms.

PMID- 21967701
TI  - Pedalium murex Linn.: an overview of its phytopharmacological aspects.
AB  - Pedalium murex Linn (family: Pedaliaceae) (P. murex) commonly known as Large
      Caltrops and Gokhru (India) is a shrub found in the Southern part, Deccan region
      of India and in some parts of Ceylon. Different parts of the plant are used to
      treat various ailments like, cough, cold and as an antiseptic. Interestingly, P.
      murex is reported traditionally to have an excellent cure in patients with
      reproductive disorders which are mainly impotency in men, nocturnal emissions,
      gonorrhoea as well as leucorrhoea in women. The plant has also benifited in
      complications like urinary track disorder as well as gastro intestinal tract
      disorders. Phytochemically the plant is popular for the presence of a
      considerable amount of diosgenin and vanillin which are regarded as an important
      source and useful starting materials for synthesizing steroidal contraceptive
      drugs and isatin alkaloids. Other phytochemicals reported in the plant includes
      quercetin, ursolic acid, caffeic acid, amino acids (glycine, histidine, tyrosine,
      threonine, aspartic acid and glutamic acid) and various classes of fatty acids
      (triacontanoic acid, nonacosane, tritriacontane, tetratriacontanyl and
      heptatriacontan-4-one). Pharmacologically, the plant have been investigated for
      antiulcerogenic, nephroprotective, hypolipidemic, aphrodisiac, antioxidant,
      antimicrobial and insecticidal activities. From all these reports it can be
      concluded that the plant were found to have a better profile with potential
      natural source for the treatment of various range of either acute or chronic
      disease. The overall database of our review article was collected from the
      scientific sources in regards with all the information of the research article
      for P. murex published so far.

PMID- 21967702
TI  - Malarial pigment does not induce MMP-2 and TIMP-2 protein release by human
      monocytes.

PMID- 21967704
TI  - Dielectric properties of organic solvents from non-polarizable molecular dynamics
      simulation with electronic continuum model and density functional theory.
AB  - Dielectric constants of electrolytic organic solvents are calculated employing
      nonpolarizable Molecular Dynamics simulation with Electronic Continuum (MDEC)
      model and Density Functional Theory. The molecular polarizabilities are obtained
      by the B3LYP/6-311++G(d,p) level of theory to estimate high-frequency refractive
      indices while the densities and dipole moment fluctuations are computed using
      nonpolarizable MD simulations. The dielectric constants reproduced from these
      procedures are evaluated to provide a reliable approach for estimating the
      experimental data. An additional feature, two representative solvents which have
      similar molecular weights but are different dielectric properties, i.e., ethyl
      methyl carbonate and propylene carbonate, are compared using MD simulations and
      the distinctly different dielectric behaviors are observed at short times as well
      as at long times.

PMID- 21967703
TI  - Limiting hepatitis C virus progression in liver transplant recipients using
      sirolimus-based immunosuppression.
AB  - Hepatitis C virus (HCV) causes progressive liver fibrosis in liver transplant
      recipients and is the principal cause of long-term allograft failure. The
      antifibrotic effects of sirolimus are seen in animal models but have not been
      described in liver transplant recipients. We reviewed 1274 liver recipients from
      2002 to 2010 and identified a cohort of HCV recipients exposed to sirolimus as
      primary immunosuppression (SRL Cohort) and an HCV Control Group of recipients who
      had never received sirolimus. Yearly protocol biopsies were done recording
      fibrosis stage (METAVIR score) with biopsy compliance of >80% at both year one
      and two. In an intent-to-treat analysis, the SRL Cohort had significantly less
      advanced fibrosis (stage >=2) compared to the HCV Control Group at year one
      (15.3% vs. 36.2%, p < 0.0001) and year two (30.1% vs. 50.5%, p = 0.001). Because
      sirolimus is sometimes discontinued for side effects, the SRL Cohort was subgroup
      stratified for sirolimus duration, showing progressively less fibrosis with
      longer sirolimus duration. Multivariate analysis demonstrated sirolimus as an
      independent predictor of minimal fibrosis at year one, and year two. This is the
      first study among liver transplant recipients with recurrent HCV to describe the
      positive impact of sirolimus in respect of reduced fibrosis extent and rate of
      progression.

PMID- 21967705
TI  - Role of retention of the condylar cartilage in open treatment of intracapsular
      condylar fractures in growing goats: three-dimensional computed tomographic
      analysis.
AB  - Our aim was to investigate the role of retention of the condylar cartilage in
      open reduction and internal fixation (ORIF) of intracapsular condylar fractures
      (ICFs) in growing goats by three-dimensional computed tomographic (CT) analysis.
      Twelve goats 6 months old were randomly divided into three groups. ICFs were
      created bilaterally in mandibular condyles and treated with ORIF. On the one side
      (n=4) the condylar cartilage was removed, and on the other side (n=4) it was
      retained. Condyles in the control group (n=4) were untouched. CT scans were taken
      immediately postoperatively, and 3 and 6 months later. The heights of the rami
      among the three groups were compared, There were significant reductions in the
      height of rami in the group from which the cartilage had been removed 3 and 6
      months postoperatively compared with controls, but no significant differences
      between control group and the group in which it had been retained. We conclude
      that retaining condylar cartilage in the ORIF for ICF of growing goats has no
      harmful effect on condylar growth, but removal can limit growth.

PMID- 21967706
TI  - Towards an integrated approach in surveillance of vector-borne diseases in
      Europe.
AB  - Vector borne disease (VBD) emergence is a complex and dynamic process.
      Interactions between multiple disciplines and responsible health and
      environmental authorities are often needed for an effective early warning,
      surveillance and control of vectors and the diseases they transmit. To fully
      appreciate this complexity, integrated knowledge about the human and the vector
      population is desirable. In the current paper, important parameters and terms of
      both public health and medical entomology are defined in order to establish a
      common language that facilitates collaboration between the two disciplines.
      Special focus is put on the different VBD contexts with respect to the current
      presence or absence of the disease, the pathogen and the vector in a given
      location. Depending on the context, whether a VBD is endemic or not, surveillance
      activities are required to assess disease burden or threat, respectively.
      Following a decision for action, surveillance activities continue to assess
      trends.

PMID- 21967707
TI  - Polyelectrolyte complex of carboxymethyl starch and chitosan as protein carrier:
      oral administration of ovalbumin.
AB  - A novel carboxymethyl starch (CMS)/chitosan polyelectrolyte complex (PEC) was
      proposed as an excipient for oral administration of ovalbumin. The dissolution of
      ovalbumin from monolithic tablets (200 mg, 2.1 * 9.6 mm, 50% loading) obtained by
      direct compression was studied. When CMS was used as an excipient, more than 70%
      of the loaded ovalbumin remained undigested after 1 h of incubation in simulated
      gastric fluid (SGF) with pepsin. The complete dissolution, after transfer of
      tablets into simulated intestinal fluid (SIF) with pancreatin, occurred within a
      total time of about 6 h. Higher protection (more than 90% stability in SGF) and
      longer dissolution (more than 13 h) were obtained with 50% CMS/50% chitosan
      physical mixture or with PEC excipients. A lower proportion of chitosan was
      needed for PEC than for the CMS/chitosan mixture to obtain a similar dissolution
      profile. The high protection against digestion by pepsin, the various release
      times and the mucoadhesion properties of these excipients based on CMS favor the
      development of suitable carriers for oral vaccinations. 

PMID- 21967708
TI  - Establishment of reference CD4+ T cell values for adult Indian population.
AB  - BACKGROUND: CD4+ T lymphocyte counts are the most important indicator of disease
      progression and success of antiretroviral treatment in HIV infection in resource
      limited settings. The nationwide reference range of CD4+ T lymphocytes was not
      available in India. This study was conducted to determine reference values of
      absolute CD4+ T cell counts and percentages for adult Indian population. METHODS:
      A multicentric study was conducted involving eight sites across the country. A
      total of 1206 (approximately 150 per/centre) healthy participants were enrolled
      in the study. The ratio of male (N = 645) to female (N = 561) of 1.14:1. The
      healthy status of the participants was assessed by a pre-decided questionnaire.
      At all centers the CD4+ T cell count, percentages and absolute CD3+ T cell count
      and percentages were estimated using a single platform strategy and lyse no wash
      technique. The data was analyzed using the Statistical Package for the Social
      Scientist (SPSS), version 15) and Prism software version 5. RESULTS: The absolute
      CD4+ T cell counts and percentages in female participants were significantly
      higher than the values obtained in male participants indicating the true
      difference in the CD4+ T cell subsets. The reference range for absolute CD4 count
      for Indian male population was 381-1565 cells/MUL and for female population was
      447-1846 cells/MUL. The reference range for CD4% was 25-49% for male and 27-54%
      for female population. The reference values for CD3 counts were 776-2785
      cells/MUL for Indian male population and 826-2997 cells/MUL for female
      population. CONCLUSION: The study used stringent procedures for controlling the
      technical variation in the CD4 counts across the sites and thus could establish
      the robust national reference ranges for CD4 counts and percentages. These ranges
      will be helpful in staging the disease progression and monitoring antiretroviral
      therapy in HIV infection in India.

PMID- 21967709
TI  - Impact of anaerobiosis strategy and bioreactor geometry on the biochemical
      response of Clostridium butyricum VPI 1718 during 1,3-propanediol fermentation.
AB  - The impact of anaerobiosis strategy on 1,3-propanediol production during
      cultivation of Clostridium butyricum VPI 1718 in different size bioreactors was
      studied. In batch trials with N2 gas infusion, the fermentation was successfully
      accomplished, regardless of initial glycerol concentration imposed and bioreactor
      geometry. However, in the absence of N2 continual sparging, significant
      variations concerning the biochemical response of the strain were observed.
      Specifically, at 1-L bioreactor, the absence of N2 infusion at high initial
      glycerol concentration induced lactate dehydrogenase activity and thus lactic
      acid synthesis, probably due to partial blockage of phosphoroclastic reaction
      caused by insufficient self-generated anaerobiosis environment. During fed-batch
      cultivation with continual N2 sparging, the strain produced ~71 g L(-1) of 1,3
      propanediol, whereas under self-generated anaerobiosis, 1,3-propanediol pathway
      was evidently restricted, as only 30.5 g L(-1) of 1,3-propanediol were finally
      produced. Apparently, N2 infusion strategy paired with bioreactor geometry can
      alter the biochemical behavior of the particular strain.

PMID- 21967710
TI  - Fermentation of Chlorella sp. for anaerobic bio-hydrogen production: influences
      of inoculum-substrate ratio, volatile fatty acids and NADH.
AB  - This study evaluated the influences of inoculum-substrate ratio (ISR), volatile
      fatty acids (VFAs) and nicotinamide adenine dinucleotide, the reduced form (NADH)
      on hydrogen production during the anaerobic fermentation of Chlorella sp. in
      batch tests at 35  degrees C. The results indicated that the hydrogen
      concentration and lag time increased when ISR decreased, and the maximum hydrogen
      production and hydrogen content, 7.13 mL/g VS and 45.3%, respectively, were
      obtained when ISR was equal to 0.3. On the other hand, VFAs concentrations
      increased with the increase of hydrogen. The NADH increased while the daily
      output of hydrogen decreased as the fermentation carried on. The results
      suggested that ISR, VFAs, and NADH were important parameters for effective
      anaerobic hydrogen production using Chlorella sp. as substrate.

PMID- 21967711
TI  - Acid tolerance of an acid mine drainage bioremediation system based on biological
      sulfate reduction.
AB  - The acid tolerance response of an AMD bioremediation system based on sulfate
      reduction was investigated. Efficient sulfate reduction was observed with a
      maximum sulfate reduction rate of 12.3+/-0.8 mg L(-1) d(-1) and easily available
      organic carbon was released during high acid treatment with an initial pH of 2.0.
      The rapid increase in sulfate reduction was observed when the extreme acid
      treatment with an initial pH of 1.0 was stopped. Column experiment on acid shock
      showed that efficient sulfate reduction was maintained while precipitation of Cu
      or Zn still occurred during extreme or high acid shock. More than 98% of Cu and
      85% of Zn were removed in the high acid column experiment with influent pH of
      2.0. The majority bacteria in the remediation system used for high acid drainage
      belonged to genera Clostridiaceae, Eubacterium, Pseudobutyrivibrio, and
      Clostridium. These findings showed high acid tolerance of the straw remediation
      system.

PMID- 21967712
TI  - Degradation kinetics of the main carbohydrates in birch wood during hot water
      extraction in a batch reactor at elevated temperatures.
AB  - Hot water extraction of wood at elevated temperatures may be a suitable method to
      produce hemicellulose-lean pulps and to recover xylan-derived products from the
      water extract. In this study, water extractions of birch wood were conducted at
      temperatures between 180 and 240  degrees C in a batch reactor. Xylan was
      extensively removed, whereas cellulose was partly degraded only at temperatures
      above 180  degrees C. Under severe extraction conditions, acetic acid content in
      the water extract was higher than the corresponding amount of acetyl groups in
      wood. In addition to oligo- and monosaccharides, considerable amounts of furfural
      and 5-hydroxymethylfurfural (HMF) were recovered from the extracts. After
      reaching a maximum, the furfural yield remained constant with increasing
      extraction time. This maximum slightly decreased with increasing extraction
      temperature, suggesting the preferential formation of secondary degradation
      products from xylose. Kinetic models fitting experimental data are proposed to
      explain degradation and conversion reactions of xylan and glucan.

PMID- 21967713
TI  - Production of carbonyl reductase by Metschnikowia koreensis.
AB  - A new strain of the yeast Metschnikowia koreensis was grown in shake flasks and a
      stirred bioreactor for the production of carbonyl reductase. The optimal
      conditions in the bioreactor for maximizing the biomass specific activity of the
      enzyme were found to be: a medium composed of glucose (20 g/L), peptone (5 g/L),
      yeast extract (5 g/L) and zinc sulfate (0.3g/L); the pH controlled at 7; the
      temperature controlled at 25  degrees C; an agitation speed of 500 rpm; and an
      aeration rate of 0.25 vvm. In the bioreactor, a biomass specific enzyme activity
      of 115.6 U/gDCW was obtained and the maximum biomass concentration was 15.3
      gDCW/L. The biomass specific enzyme activity obtained in the optimized bioreactor
      culture was 11-fold higher than the best result achieved in shake flasks. The
      bioreactor culture afforded a 2.7-fold higher biomass concentration than could be
      attained in shake flasks.

PMID- 21967714
TI  - Microalgal system for treatment of effluent from poultry litter anaerobic
      digestion.
AB  - The potential of mixotrophic microalgae to utilize poultry litter anaerobic
      digester (AD) effluent (PLDE) as nutritional growth medium was evaluated. Three
      algal strains viz. Chlorella minutissima, Chlorella sorokiniana and Scenedesmus
      bijuga and their consortium showed significant biomass productivity in 6% (v/v)
      concentration of PLDE in deionized water. Multiple booster dosage of PLDE
      supported better growth relative to a single dose PLDE. The maximum biomass
      productivity of 76 mg L(-1) d(-1) was recorded. The biomass was rich in protein
      (39% w/w) and carbohydrates (22%) while lipids (<10%) were low, making it most
      suitable as an animal feed supplement. The mixotrophic algae showed sustainable
      growth against variations in PLDE composition in different AD batches, thus
      proving to be a suitable candidate for large scale wastewater treatment with
      concomitant production of renewable biomass feedstock for animal feed and
      bioenergy applications.

PMID- 21967715
TI  - Differential induction, purification and characterization of cold active lipase
      from Yarrowia lipolytica NCIM 3639.
AB  - The production, purification and characterization of cold active lipases by
      Yarrowia lipolytica NCIM 3639 is described. The study presents a new finding of
      production of cell bound and extracellular lipase activities depending upon the
      substrate used for growth. The strain produced cell bound and extracellular
      lipase activity when grown on olive oil and Tween 80, respectively. The organism
      grew profusely at 20  degrees C and at initial pH of 5.5, producing maximum
      extracellular lipase. The purified lipase has a molecular mass of 400 kDa having
      20 subunits forming a multimeric native protein. Further the enzyme displayed an
      optimum pH of 5.0 and optimum temperature of 25  degrees C. Peptide mass finger
      printing reveled that some peptides showed homologues sequence (42%) to Yarrowia
      lipolytica LIP8p. The studies on hydrolysis of racemic lavandulyl acetate
      revealed that extracellular and cell bound lipases show preference over the
      opposite antipodes of irregular monoterpene, lavandulyl acetate.

PMID- 21967716
TI  - Effects of solids retention time on methanogenesis in anaerobic digestion of
      thickened mixed sludge.
AB  - When a bench-scale digester fed thickened mixed sludge was operated over an SRT
      range of 4-20 days, removal efficiencies for total chemical oxygen demand and
      volatile suspended solids declined with decreasing SRT (especially <10 days), but
      methanogenesis was stable for SRT as low as 5 days. Quantitative PCR analyses
      showed that methanogens declined steadily for SRT<10 days, with the acetate
      cleaving Methanosaetaceae becoming more dominant. Clone-library analyses
      indicated significant shifts in bacterial population from 20 to 4 day SRT:
      declining Chloroflexi (28 to 4.5%) and Syntrophomonas (9 to 0%), but increasing
      Bacteroidetes (12.5 to 20%) and two acetogenic genera belonging to the phyla
      Firmicutes and Spirochaetales (6.3 to 12%). Thus, the decrease in the apparent
      hydrolysis constant (khyd-app) with higher SRT and the process limiting size of
      Methanosaetaceae with the lower SRT are proactive signs for defining rate
      limitation in anaerobic digestion.

PMID- 21967717
TI  - Differential regulation of fatty acid biosynthesis in two Chlorella species in
      response to nitrate treatments and the potential of binary blending microalgae
      oils for biodiesel application.
AB  - This study was undertaken to investigate the effects of different nitrate
      concentrations in culture medium on oil content and fatty acid composition of
      Chlorella vulgaris (UMT-M1) and Chlorella sorokiniana (KS-MB2). Results showed
      that both species produced significant higher (p<0.05) oil content at nitrate
      ranging from 0.18 to 0.66 mM with C. vulgaris produced 10.20-11.34% dw, while C.
      sorokiniana produced 15.44-17.32% dw. The major fatty acids detected include
      C16:0, C18:0, C18:1, C18:2 and C18:3. It is interesting to note that both species
      displayed differentially regulated fatty acid accumulation patterns in response
      to nitrate treatments at early stationary growth phase. Their potential use for
      biodiesel application could be enhanced by exploring the concept of binary
      blending of the two microalgae oils using developed mathematical equations to
      calculate the oil mass blending ratio and simultaneously estimated the weight
      percentage (wt.%) of desirable fatty acid compositions.

PMID- 21967718
TI  - Effects of sediment pretreatment on the performance of sediment microbial fuel
      cells.
AB  - In the present study, the effects of different pretreatment methods for sediments
      on the performance of sediment microbial fuel cells (SMFCs) were evaluated.
      Autoclaved (30 and 60 min), and heated (150  degrees C, 3 h) sediments
      demonstrated high power density, compared with control and heated (60  degrees C,
      3 h) sediments. An SMFC with heated (60  degrees C, 3 h) sediment was found to
      easily form a biocathode. The power density of an SMFC with heated (150  degrees
      C, 3 h) sediment was 214 mW m(-2) on day 24. Furthermore, autoclaved (30 and 60
      min) and heated (3 h, 60 and 150  degrees C) sediments accelerated the production
      of dissolved organic matter (DOM). The DOM in heated (60  degrees C, 3 h)
      sediments had larger molecular sizes. The present study demonstrates that SMFCs
      can have high power density and high loss on ignition removal efficiencies when
      produced from sediments by suitable pretreatment methods.

PMID- 21967719
TI  - Improving the environmental profile of wood panels via co-production of ethanol
      and acetic acid.
AB  - The oriented strand board (OSB) biorefinery is an emerging technology that could
      improve the building, transportation, and chemical sectors' environmental
      profiles. By adding a hot water extraction stage to conventional OSB panel
      manufacturing, hemicellulose polysaccharides can be extracted from wood strands
      and converted to renewably sourced ethanol and acetic acid. Replacing fossil
      based gasoline and acetic acid has the potential to reduce greenhouse gas (GHG)
      emissions, among other possible impacts. At the same time, hemicellulose
      extraction could improve the environmental profile of OSB panels by reducing the
      level of volatile organic compounds (VOCs) emitted during manufacturing. In this
      study, the life cycle significance of such GHG, VOC, and other emission
      reductions was investigated. A process model was developed based on a mix of
      laboratory and industrial-level mass and energy flow data. Using these data a
      life cycle assessment (LCA) model was built. Sensitive process parameters were
      identified and used to develop a target production scenario for the OSB
      biorefinery. The findings suggest that the OSB biorefinery's deployment could
      substantially improve human and ecosystem health via reduction of select VOCs
      compared to conventionally produced OSB, gasoline, and acetic acid. Technological
      advancements are needed, however, to achieve desirable GHG reductions.

PMID- 21967720
TI  - Speciation of dissolved inorganic arsenic by diffusive gradients in thin films:
      selective binding of AsIII by 3-mercaptopropyl-functionalized silica gel.
AB  - A diffusive gradients in thin films (DGT) technique for selectively measuring
      As(III) utilizes commercially available 3-mercaptopropyl-functionalized silica
      gel. Deployment of the new technique alongside the Metsorb-DGT for total
      inorganic arsenic allows the calculation of As(III) directly and As(V) by
      difference. Uptake of As(III) by mercapto-silica was quantitative and elution
      with a mixture of 1 mol L(-1) HNO(3) and 0.01 mol L(-1) KIO(3) gave a recovery of
      85.6 +/- 1.7%. DGT validation experiments showed linear accumulation of As(III)
      over time (R(2) > 0.998). Accumulation was unaffected by varying ionic strength
      (0.0001-0.75 mol L(-1) NaNO(3)) and pH (3.5-8.5). Deployment of mercapto-silica
      DGT and Metsorb DGT in seawater spiked with As(III) and As(V) demonstrated the
      ability of the combined approach to accurately quantify both species in the
      presence of potential competing ions. Ferrihydrite DGT, which has been previously
      reported for the measurement of total inorganic arsenic, was evaluated in
      seawater and shown to underestimate both As(III) and As(V) at longer deployment
      times (72 h). Reproducibility of the new mercapto-silica DGT technique was good
      (relative standard deviations < 9%), and the average method detection limit was
      sufficiently low to allow quantification of ultratrace concentrations of As(III)
      (0.03 MUg L(-1); 72 h deployment).

PMID- 21967722
TI  - Quality improvement curricula in pediatric residency education: obstacles and
      opportunities.

PMID- 21967721
TI  - The patient-centered medical home, practice patterns, and functional outcomes for
      children with attention deficit/hyperactivity disorder.
AB  - OBJECTIVE: To determine whether children with attention deficit/hyperactivity
      disorder (ADHD) receive care in a patient-centered medical home (PCMH) and how
      that relates to their ADHD treatment and functional outcomes. METHODS: Cross
      sectional analysis of the 2007 National Survey for Children's Health, a
      nationally representative survey of 91,642 parents. This analysis covers 5169
      children with parent-reported ADHD ages 6-17. The independent variable is
      receiving care in a PCMH. Main outcome measures are receiving ADHD medication,
      mental health specialist involvement, and functional outcomes (difficulties with
      participation in activities, attending school, making friends; having problem
      behaviors; missed school days; and number of times parents contacted by school).
      RESULTS: Only 44% of children with ADHD received care in a PCMH. Children with
      ADHD receiving care in a PCMH compared with those who did not were more likely to
      receive medication for ADHD (odds ratio [OR], 1.4; 95% confidence interval [CI],
      1.1-1.9); less likely to have mental health specialist involvement (OR, 0.6; 95%
      CI, 0.4-0.7); less likely to have difficulties participating in activities (OR,
      0.6; 95% CI 0.4-0.8), making friends (OR, 0.6; 95% CI, 0.5-0.9), and attending
      school (OR, 0.4; 95% CI, 0.3-06); less likely to have problem behaviors (OR 0.6;
      95% CI 0.5-0.9); had fewer missed school days (beta = -1.5, 95% CI -2.4 to -0.5);
      and parents were contacted by school less frequently (beta = -0.2, 95% CI -0.3 to
      -0.1). CONCLUSIONS: For children with ADHD, receiving care in a PCMH is
      associated with practice pattern change and better outcomes. The PCMH may
      represent a promising opportunity to improve quality of care and outcomes for
      children with ADHD.

PMID- 21967723
TI  - Colloidal quantum dot photovoltaics: a path forward.
AB  - Colloidal quantum dots (CQDs) offer a path toward high-efficiency photovoltaics
      based on low-cost materials and processes. Spectral tunability via the quantum
      size effect facilitates absorption of specific wavelengths from across the sun's
      broad spectrum. CQD materials' ease of processing derives from their synthesis,
      storage, and processing in solution. Rapid advances have brought colloidal
      quantum dot photovoltaic solar power conversion efficiencies of 6% in the latest
      reports. These achievements represent important first steps toward commercially
      compelling performance. Here we review advances in device architecture and
      materials science. We diagnose the principal phenomenon-electronic states within
      the CQD film band gap that limit both current and voltage in devices-that must be
      cured for CQD PV devices to fulfill their promise. We close with a prescription,
      expressed as bounds on the density and energy of electronic states within the CQD
      film band gap, that should allow device efficiencies to rise to those required
      for the future of the solar energy field.

PMID- 21967724
TI  - Comment on time-varying eddy currents effects on diffusion-weighting echo-planar
      imaging.
AB  - This commentary addresses the recent paper entitled "Dynamic correction of
      artifacts due to susceptibility effects and time-varying eddy currents in
      diffusion tensor imaging" (Truong et al., 2011) and discusses their findings in
      relation to previous studies from the late 1990s that showed equivalent findings
      regarding the complex time-varying nature of eddy currents during the imaging
      readout. The similarities between the findings from these studies are
      highlighted, and their possible implications for present commonly used eddy
      current reduction methods are discussed.

PMID- 21967725
TI  - Is there a correlation between hippocampus and amygdala volume and olfactory
      function in healthy subjects?
AB  - Both amygdala (AG) and hippocampus (HC) are integral parts of the olfactory
      system. The present study, including a large number of healthy subjects, was
      performed to compare HC and AG volumes, measured by manual tracing, in relation
      to specific olfactory functions, including odor threshold, discrimination,
      identification, and odor memory tasks. It also aimed to provide age-related
      normative data about the volume of the HC and AG. A total of 117 healthy
      volunteers participated (age range 19-77 years, mean age 37 years; 62 women, 55
      men). Using the "Sniffin' Sticks", subjects received lateralized tests for odor
      threshold, and odor discrimination. In addition, an odor memory and an odor
      identification task were performed bilaterally. A Mini-Mental-State test excluded
      dementia. MR scans were performed using a 1.5 T scanner for later manual
      volumetric measurements. Volumetric measurements exhibited a good
      reproducibility. The average volume for the right HC was 3.29 cm(3) (SD 0.47),
      for the left HC it was 3.15 cm(3) (SD 0.47). The average right AG had a volume of
      1.60 cm(3) (SD 0.31), left 1.59 cm(3) (SD 0.3). Increasing age was accompanied by
      a decrease of HC and AG volumes, which were much more pronounced for the right
      compared to the left side. Only the volume of the right HC showed a small but
      significant correlation with odor threshold (r(117)=0.21; p=0.02). Importantly,
      this correlation was not mediated by age as indicated by the significant partial
      correlation when controlling for age (r(114)=0.18; p=0.049). In conclusion, the
      present data obtained in a relatively large group of subjects demonstrates a
      small correlation between the volume of the HC, as an integral part of the
      olfactory system, and smell function. In addition, these data can be used as the
      basis for normative values of HC and AG volumes, separately for men, women and
      different age groups. This is of potential interest in diseases with acute or
      chronic impairment of olfactory function, in metabolic or neurodegenerative
      diseases or in disorders with damage of areas involved in adult neurogenesis.

PMID- 21967726
TI  - Microstructural white matter abnormalities in type 2 diabetes mellitus: a
      diffusion tensor imaging study.
AB  - This study investigated whether diffusion tensor imaging (DTI) could identify
      potential abnormalities in type 2 diabetes mellitus (T2DM) patients without
      cognitive complaints compared to healthy controls. In addition, the existence of
      associations between diffusion measures and clinical parameters was examined.
      Forty T2DM patients and 97 non-diabetic controls completed a clinical and
      biochemistry examination. Structural MRI scans (DTI, T1, T2, FLAIR) were
      subsequently acquired with a 1.5 Tesla scanner. In addition to a global DTI
      analysis, voxel-based analysis was performed on the fractional anisotropy (FA),
      mean diffusivity (MD), and axial (AD) and transverse (TD) diffusivity maps to
      investigate regions that exhibit (i) WM differences between patients and
      controls; and (ii) associations between clinical measurements and these DTI
      indices. There were no significant differences in age, gender, and WM
      hyperintensity scores derived by the conventional MRI scans between controls and
      T2DM patients. For the T2DM patients, however, the MD of the brain parenchyma was
      significantly increased compared to controls and was positively correlated with
      disease duration. The voxel based analyses revealed (i) a significantly decreased
      FA in the bilateral frontal WM compared to controls which was mainly caused by an
      increased TD and not a decreased AD within these regions; (ii) a significant
      association between disease duration and microstructural properties in several
      brain regions including bilateral cerebellum, temporal lobe WM, right caudate,
      bilateral cingulate gyrus, pons, and parahippocampal gyrus. Our findings indicate
      that microstructural WM abnormalities and associations with clinical measurements
      can be detected with DTI in T2DM patients.

PMID- 21967727
TI  - Grey matter abnormalities within cortico-limbic-striatal circuits in acute and
      weight-restored anorexia nervosa patients.
AB  - Functional disturbances within cortico-striatal control systems have been
      implicated in the psychobiology (i.e. impaired cognitive-behavioral flexibility,
      perfectionist personality) of anorexia nervosa. The aim of the present study was
      to investigate the morphometry of brain regions within cortico-striatal networks
      in acute anorexia nervosa (AN) as well as long-term weight-restored anorexia
      nervosa (AN-WR) patients. A total of 39 participants: 12 AN, 13 AN-WR patients,
      and 14 healthy controls (HC) underwent high-resolution, T1-weighted magnetic
      resonance imaging (MRI), a cognitive-behavioral flexibility task, and a
      psychometric assessment. Group differences in local grey matter volume (GMV) were
      analyzed using whole brain voxel-based morphometry (VBM) and brain-atlas based
      automatic volumetry computation (IBASPM). Individual differences in total GMV
      were considered as a covariate in all analyses. In the regional brain
      morphometry, AN patients, as compared to HC, showed decreased GMVs (VBM and
      volumetry) in the anterior cingulate cortex (ACC), the supplementary motor area
      (SMA), and in subcortical regions (amygdala, putamen: VBM only). AN-WR compared
      to HC showed decreased GMV (VBM and volumetry) in the ACC and SMA, whereas GMV of
      the subcortical region showed no differences. The findings of the study suggest
      that structural abnormalities of the ACC and SMA were independent of the disease
      stage, whereas subcortical limbic-striatal changes were state dependent.

PMID- 21967728
TI  - Development and psychometric testing of an instrument to evaluate cognitive
      skills of evidence based practice in student health professionals.
AB  - BACKGROUND: Health educators need rigorously developed instruments to evaluate
      cognitive skills relating to evidence based practice (EBP). Previous EBP
      evaluation instruments have focused on the acquisition and appraisal of the
      evidence and are largely based in the medical profession. The aim of this study
      was to develop and validate an EBP evaluation instrument to assess EBP cognitive
      skills for entry-level health professional disciplines. METHODS: The Fresno test
      of competence in evidence based medicine was considered in the development of the
      'Knowledge of Research Evidence Competencies' instrument (K-REC). The K-REC was
      reviewed for content validity. Two cohorts of entry-level students were recruited
      for the pilot study, those who had been exposed to EBP training (physiotherapy
      students, n = 24), and who had not been exposed to EBP training (human movement
      students, n = 76). The K-REC was administered to one cohort of students (n = 24)
      on two testing occasions to evaluate test-retest reliability. Two raters
      independently scored the first test occasion (n = 24) to evaluate the inter-rater
      reliability of the marking guidelines. Construct validity was assessed by
      comparison of the two groups, 'exposed' and 'non-exposed', and the percentage of
      students achieving a 'pass' score in each of these groups. Item difficulty was
      established. RESULTS: Among the 100 participants (24 EBP 'exposed', and 76 EBP
      'non-exposed' students), there was a statistically significant (p < 0.0001)
      difference in the total K-REC scores. The test-retest and inter-rater reliability
      of the individual items and total scores ranged from moderate to excellent
      (measured by Cohen's Kappa and ICC, range: 0.62 to perfect agreement).
      CONCLUSIONS: The K-REC instrument is a valid and reliable evaluation instrument
      of cognitive skills of EBP in entry-level student health professionals. The
      instrument is quick to disseminate and easy to score, making it a suitable
      instrument for health educators to employ to evaluate students' knowledge of EBP
      or in the evaluation of entry-level EBP training.

PMID- 21967729
TI  - Effects of flushing and hormonal treatment on reproductive performance of Iranian
      Markhoz goats.
AB  - Forty-eight Iranian Markhoz goats were allocated to six groups (n = 8) to study
      the effect of flushing and hormonal treatments on reproductive performance.
      Treatments were divided into two categories including, hormonal treatments and
      flushing. The goats in each group were fed the same basal ration and received one
      of the following treatments: Groups A and B--injection of GnRH and equine
      chorionic gonadotropin (eCG) respectively; Groups C, D and E--a supplement of
      barley grain, soybean oil and sunflower oil in flushing diets, respectively, were
      offered and Group F--control (only received basal diet). In the flushing
      treatments, only the source of energy was different between rations. Both
      hormonal treatments and flushing treatments improved fertility and kidding rates.
      Treatment B with 16 and control with seven kids represented the highest and the
      lowest number of progeny respectively. Among flushing treatments, group C
      resulted in the highest number of kids being 15. Oestrogen levels in follicular
      phase increased with the injection of eCG and consumption of barley grain. GnRH
      injection and consumption of oil sources in the diet increased blood progesterone
      levels during ovulation and post-ovulation periods. Under current market
      conditions, using hormone or flushing can be profitable for Markhoz goats
      farmers.

PMID- 21967730
TI  - Comparison of humoral neuroinflammation and adhesion molecule expression in two
      models of experimental intracerebral hemorrhage.
AB  - BACKGROUND: Inflammatory cascades contribute to secondary injury after
      intracerebral hemorrhage (ICH) via humoral factors and cell-mediated
      cytotoxicity. Several experimental models were previously developed to analyze
      post-hemorrhagic neuroinflammation. However, neuroinflammatory markers have not
      been compared face-to-face between these models so far, and therefore,
      pathophysiological conclusions drawn from only one individual model may not be
      valid. METHODS: We compared neuroinflammatory pathways in the two most common
      murine models: striatal injection of autologous blood or collagenase. Expression
      of pro- and anti-inflammatory cytokines (IL-1, TNF-alpha, IFN-gamma, IL-6, TGF
      beta and IL-10) as well adhesion molecule expression (VCAM-1, ICAM-1) was
      analyzed by RT-PCR at several time points after ICH induction. Outcome and
      physiological parameters were compared between the models. RESULTS: Both models
      induced a profound and dynamic increase in the expression of pro-inflammatory
      cytokines and adhesion molecules. However, blood injection resulted in
      significantly more pronounced alteration of these markers than collagenase
      injection. This difference was associated with worse outcome after blood
      injection compared to the collagenase model despite equal ICH volumes.
      CONCLUSIONS: This is the first study performing a face-to-face comparison of
      neuroinflammatory pathways in the two most widely used murine ICH models,
      revealing substantial differences between the models. This discrepancies need to
      be taken into account in designing future studies employing experimental ICH
      models, especially when analyzing neuroinflammatory pathways and therapies.

PMID- 21967731
TI  - More effective assessment of adverse effects and comorbidities in epilepsy:
      results of a Phase II communication study.
AB  - Research was conducted to evaluate conversations about epilepsy between community
      based neurologists and patients. Adverse effects of antiepileptic drugs and
      mood/behavioral issues were infrequently discussed, and neurologists and patients
      disagreed about these issues postvisit. Follow-up research was conducted to
      assess the impact of a previsit assessment tool on discussions of epilepsy.
      Twenty neurologists reviewed a tool incorporating questions from validated
      instruments (Adverse Events Profile [AEP] and Neurological Disorders Depression
      Inventory for Epilepsy [NDDI-E]). Naturally occurring interactions between
      neurologists and 60 patients were recorded. Neurologists and patients were
      interviewed separately. All components were transcribed and analyzed using
      sociolinguistics. Using the previsit assessment tool increased the number of
      discussions about adverse effects and mood/behavioral issues and increased
      neurologist-patient agreement about issues postvisit. Visit length did not
      increase significantly when the tool was used. Ten months after follow-up
      research, 50% of neurologists reported continuing to use the tool in everyday
      practice with patients with epilepsy.

PMID- 21967732
TI  - Functional upregulation of system xc- by fibroblast growth factor-2.
AB  - The cystine/glutamate antiporter (system xc-) is a Na(+)-independent amino acid
      transport system. Disruption of this system may lead to multiple effects in the
      CNS including decreased cellular glutathione. Since multiple neurological
      diseases involve glutathione depletion, and disruption of growth factor signaling
      has also been implicated in these diseases, it is possible that some growth
      factors effects are mediated by regulation of system xc-. We tested the growth
      factors fibroblast growth factor-2 (FGF-2), insulin-like growth factor-1 (IGF-1),
      neuregulin-1 (NRG), neurotrophin-4 (NT-4), and brain derived neurotrophic factor
      (BDNF) on system xc- mediated 14C-cystine uptake in mixed neuronal and glial
      cortical cultures. Only FGF-2 significantly increased cystine uptake. The effect
      was observed in astrocyte-enriched cultures, but not in cultures of neurons or
      microglia. The increase was blocked by the system xc- inhibitor (s)-4
      carboxyphenylglycine, required at least 12 h FGF-2 treatment, and was prevented
      by the protein synthesis inhibitor cycloheximide. Kinetic analysis indicated FGF
      2 treatment increased the V(max) for cystine uptake while the K(m) remained the
      same. Quantitative PCR showed an increase in mRNA for xCT, the functional subunit
      of system xc-, beginning at 3 h of FGF-2 treatment, with a dramatic increase
      after 12 h. Blocking FGFR1 with PD 166866 blocked the FGF-2 effect. Treatment
      with a PI3-kinase inhibitor (LY-294002) or a MEK/ERK inhibitor (U0126) for 1 h
      prior to and during the FGF-2 treatment, each partially blocked the increased
      cystine uptake. The upregulation of system xc- by FGF-2 may be responsible for
      some of the known physiological actions of FGF-2. This article is part of a
      Special Issue entitled 'Post-Traumatic Stress Disorder'.

PMID- 21967733
TI  - Neuropsychological performance in OCD: a study in medication-naive patients.
AB  - BACKGROUND: Obsessive-compulsive disorder (OCD) is associated with impairments in
      multiple neuropsychological domains but the findings are rather inconsistent
      across studies. One potential reason for poor replication is the confounding
      influence of medications. There is limited research on neuropsychological
      performance in medication-naive, never treated OCD patients. METHODS: In this
      study, we assessed 31 medication-naive, never-treated, DSM-IV OCD patients free
      of comorbid major depression and 31 healthy controls individually matched for
      age, gender and years of education, with tests of attention, executive function,
      memory reasoning and visuo-spatial function. RESULTS: Medication-naive OCD
      patients did not significantly differ from healthy controls on most
      neuropsychological tests. Patients performed somewhat poorly only on the highest
      goal hierarchy of the Tower of London (TOL) test (p=0.001, effect size=0.68).
      CONCLUSIONS: It is intriguing to find that symptomatic, drug-naive OCD patients
      did not significantly differ from healthy controls on most neuropsychological
      tests. Our finding of medium effect size on TOL highest goal hierarchy test
      suggests that brain regions outside the affective orbitofrontal loop may also be
      perhaps involved in OCD. This finding however needs replication because of modest
      effect size. Future studies should focus on studying medication-naive, co
      morbidity-free patients and relatives using symptom dimensions for consistent and
      robust findings.

PMID- 21967734
TI  - Ligand-based autotaxin pharmacophore models reflect structure-based docking
      results.
AB  - The autotaxin (ATX) enzyme exhibits lysophospholipase D activity responsible for
      the conversion of lysophosphatidyl choline to lysophosphatidic acid (LPA). ATX
      and LPA have been linked to the initiation of atherosclerosis, cancer
      invasiveness, and neuropathic pain. ATX inhibition therefore offers currently
      unexploited therapeutic potential, and substantial interest in the development of
      ATX inhibitors is evident in the recent literature. Here we report the
      performance-based comparison of ligand-based pharmacophores developed on the
      basis of different combinations of ATX inhibitors in the training sets against an
      extensive database of compounds tested for ATX inhibitory activity, as well as
      with docking results of the actives against a recently reported ATX crystal
      structure. In general, pharmacophore models show better ability to select active
      ATX inhibitors binding in a common location when the ligand-based superposition
      shows a good match to the superposition of actives based on docking results. Two
      pharmacophore models developed on the basis of competitive inhibitors in
      combination with the single inhibitor crystallized to date in the active site of
      ATX were able to identify actives at rates over 40%, a substantial improvement
      over the <10% representation of active site-directed actives in the test set
      database.

PMID- 21967735
TI  - Sirolimus is coming of age.

PMID- 21967736
TI  - Complaints with encounters in healthcare - men's experiences.
AB  - Good encounters within healthcare are important for the manner in which ill
      people facilitate their health and their perception of quality of care. Research
      about quality of care are important, but point out that dissatisfaction with
      healthcare may in the future be even more common regarding the demands for a more
      effective healthcare. The aim of this study was therefore to describe experiences
      of dissatisfaction with encounters in healthcare among men who personally filed a
      complaint to the Patients' Advisory Committee in the county council. Qualitative
      data were collected in semi-structured interviews with a purposive sample of nine
      men who have filed a complaint to the Patients' Advisory Committee. The analysis
      resulted in two categories: being met with a disrespectful manner and not
      receiving a personal apology. The results in the first category describe that the
      men were treated with disrespect and suspicions by healthcare professionals. This
      was related to lack of communication which made the men sensitive to negative
      attitudes on the part of professionals. The results in the second category show
      that the men expected amends to be made in form of a personal apology about the
      dissatisfaction. The men were given no opportunities to influence the encounters
      and the professionals were unconscious of their behaviour in form of bad
      treatment. In conclusion, the results indicate the importance of meeting patients
      and their relatives with respect and dignity, listening to their experiences and
      proceeding with the treatment without insulting anyone as a person.

PMID- 21967737
TI  - One-pot synthesis of highly folded microparticles by suspension polymerization.
AB  - A facile method of preparing highly folded cross-linked polymeric microparticles
      has been developed via one-pot suspension polymerization under high-speed
      homogenization. The wrinkles result from the evaporation of solvent in the cross
      linked microparticles. The effects of microparticle cross-linking density and
      solvent on the polymer have been studied in detail. It was found that a medium
      cross-linking density (DVB/St = 0.5 by weight) is optimal for producing the most
      folded surface and the higher the solvent content, the deeper the surface
      wrinkles. This method is very simple and in principle can be applied to produce
      wrinkled microparticles with other chemical compositions.

PMID- 21967740
TI  - Naturally occurring genotype 2b/1a hepatitis C virus in the United States.
AB  - BACKGROUND: Hepatitis C Virus (HCV) infected patients are frequently repeatedly
      exposed to the virus, but very few recombinants between two genotypes have been
      reported. FINDINGS: We describe the discovery of an HCV recombinant using a
      method developed in a United States clinical lab for HCV genotyping that employs
      sequencing of both 5' and 3' portions of the HCV genome. Over twelve months, 133
      consecutive isolates were analyzed, and a virus from one patient was found with
      discordant 5' and 3' sequences suggesting it was a genotype 2b/1a recombinant. We
      ruled out a mixed infection and mapped a recombination point near the NS2/3
      cleavage site. CONCLUSIONS: This unique HCV recombinant virus described shares
      some features with other recombinant viruses although it is the only reported
      recombinant of a genotype 2 with a subtype 1a. This recombinant represents a
      conundrum for current clinical treatment guidelines, including treatment with
      protease inhibitors. This recombinant is also challenging to detect by the most
      commonly employed methods of genotyping that are directed primarily at the 5'
      structural portion of the HCV genome.

PMID- 21967738
TI  - Platinum resistance in breast and ovarian cancer cell lines.
AB  - Breast and ovarian cancers are among the 10 leading cancer types in females with
      mortalities of 15% and 6%, respectively. Despite tremendous efforts to conquer
      malignant diseases, the war on cancer declared by Richard Nixon four decades ago
      seems to be lost. Approximately 21,800 women in the US will be diagnosed with
      ovarian cancer in 2011. Therefore, its incidence is relatively low compared to
      breast cancer with 207.090 prognosed cases in 2011. However, overall survival
      unmasks ovarian cancer as the most deadly gynecological neoplasia. Platinum-based
      chemotherapy is emerging as an upcoming treatment modality especially in triple
      negative breast cancer. However, in ovarian cancer Platinum-complexes for a long
      time are established as first line treatment. Emergence of a resistant phenotype
      is a major hurdle in curative cancer therapy approaches and many scientists
      around the world are focussing on this issue. This review covers new findings in
      this field during the past decade.

PMID- 21967741
TI  - Characterization of aquatic particles by direct FTIR analysis of filters and
      quantification of elemental and molecular compositions.
AB  - This paper presents the first characterization of aquatic particles and
      particulate organic matter (POM) by attenuated total reflectance infrared
      spectroscopy (ATR-FTIR) using particles deposited on filters. Particles from 30
      water samples from the St. Lawrence System (Canada) were analyzed. ATR-FTIR
      spectra revealed changes in numerous organic and inorganic functional group
      contents. Particles from marine waters contained POM enriched in amide, N-H, and
      aliphatic groups, while terrigenous POM had more COO(-)/COOH and aromatic groups.
      The spectra showed the selective degradation of amide, N-H, aliphatic, and
      carbohydrate-like structures during the sinking of the particles. Partial least
      squares (PLS) regression of the ATR-FTIR spectra was used to quantify 12
      important elemental and molecular parameters, such as amino acids, bacterial
      biomarkers, and degradation indices. Most parameters were quantified with good
      accuracy compared to conventional methods (<15% error). The spectral regions
      leading to the best quantifications and the PLS loadings revealed that aromatic
      cycles, other unsaturated structures, and COO(-)/COOH groups were degraded at a
      much slower rate than N-molecules, such as amino acids, and carbohydrates. Marine
      POM was enriched in CH(3) groups. CH(3) groups appeared highly labile and
      abundant in bacterial POM. ATR-FTIR represents a new and powerful method for a
      rapid, inexpensive, and nondestructive characterization of particles collected by
      filtration revealing important biogeochemical processes involving POM.

PMID- 21967742
TI  - Fabrication of collagen-elastin-bound peptide microtubes for mammalian cell
      attachment.
AB  - In this work we have designed self-assembled peptide-based microconstructs and
      examined their interactions with elastin and collagen for potential application
      as scaffolds for chondrocyte cell attachment. Being biological in nature, peptide
      based nano- and microstructures have intrinsic molecular recognition properties
      which allow extensive chemical, conformational and functional diversity. We have
      synthesized a new peptide bolaamphiphile, bis(N-alpha-amido-val)-1,5-pentane
      dicarboxylate, and examined its self-assembly at varying pH values. The formation
      of high-density networks of nano- and microtubular structures was found to be in
      the range of pH 4-6. The formed microtubes were then covalently bound to varying
      concentrations of the extracellular matrix protein elastin, a versatile protein
      that allows for an extensive array of physical and chemical modifications to
      attune properties towards diverse necessities of biomedical applications. We
      found that binding to microtubes was concentration dependent. The morphological
      and chemical changes complementing the processes of self-assembly and binding to
      elastin were examined by electron microscopic and spectroscopic methods.
      Furthermore, we also incorporated the extracellular matrix protein type-I
      collagen, a critical constituent for designing biocompatible scaffolds, into the
      elastin functionalized micro-tubes. Since the main goal is to develop highly
      biocompatible protein functionalized microstructures that support cellular
      interactions, we examined the interactions of the microcomposites with
      chondrocyte cell line, in order to assess the biocompatibility and interaction
      between the microconstructs and the cells. The designed elastin and collagen
      bound peptide microtubes may potentially serve as a new class of biomaterials by
      promoting cell growth and proliferation. 

PMID- 21967744
TI  - Technical phosphoproteomic and bioinformatic tools useful in cancer research.
AB  - Reversible protein phosphorylation is one of the most important forms of
      cellular regulation. Thus, phosphoproteomic analysis of protein phosphorylation
      in cells is a powerful tool to evaluate cell functional status. The importance of
      protein kinase-regulated signal transduction pathways in human cancer has led to
      the development of drugs that inhibit protein kinases at the apex or intermediary
      levels of these pathways. Phosphoproteomic analysis of these signalling pathways
      will provide important insights for operation and connectivity of these pathways
      to facilitate identification of the best targets for cancer therapies. Enrichment
      of phosphorylated proteins or peptides from tissue or bodily fluid samples is
      required. The application of technologies such as phosphoenrichments, mass
      spectrometry (MS) coupled to bioinformatics tools is crucial for the
      identification and quantification of protein phosphorylation sites for advancing
      in such relevant clinical research. A combination of different phosphopeptide
      enrichments, quantitative techniques and bioinformatic tools is necessary to
      achieve good phospho-regulation data and good structural analysis of protein
      studies. The current and most useful proteomics and bioinformatics techniques
      will be explained with research examples. Our aim in this article is to be
      helpful for cancer research via detailing proteomics and bioinformatic tools.

PMID- 21967745
TI  - In silico characterization of microbial electrosynthesis for metabolic
      engineering of biochemicals.
AB  - BACKGROUND: A critical concern in metabolic engineering is the need to balance
      the demand and supply of redox intermediates such as NADH. Bioelectrochemical
      techniques offer a novel and promising method to alleviate redox imbalances
      during the synthesis of biochemicals and biofuels. Broadly, these techniques
      reduce intracellular NAD+ to NADH and therefore manipulate the cell's redox
      balance. The cellular response to such redox changes and the additional reducing
      power available to the cell can be harnessed to produce desired metabolites. In
      the context of microbial fermentation, these bioelectrochemical techniques can be
      used to improve product yields and/or productivity. RESULTS: We have developed a
      method to characterize the role of bioelectrosynthesis in chemical production
      using the genome-scale metabolic model of E. coli. The results in this paper
      elucidate the role of bioelectrosynthesis and its impact on biomass growth,
      cellular ATP yields and biochemical production. The results also suggest that
      strain design strategies can change for fermentation processes that employ
      microbial electrosynthesis and suggest that dynamic operating strategies lead to
      maximizing productivity. CONCLUSIONS: The results in this paper provide a
      systematic understanding of the benefits and limitations of bioelectrochemical
      techniques for biochemical production and highlight how electrical enhancement
      can impact cellular metabolism and biochemical production.

PMID- 21967746
TI  - Thermally triggered assembly of cationic graft copolymers containing 2-(2
      methoxyethoxy)ethyl methacrylate side chains.
AB  - Thermoresponsive copolymers continue to attract a great deal of interest in the
      literature. In particular, those based on ethylene oxide-containing methacrylates
      have excellent potential for biomaterial applications. Recently, some of us
      reported a study of thermoresponsive cationic graft copolymers containing poly(N
      isopropylacrylamide), PNIPAm, (Liu et al., Langmuir, 24, 7099). Here, we report
      an improved version of this new family of copolymers. In the present study, we
      replaced the PNIPAm side chains with poly(2-(2-methyoxyethoxy)ethylmethacrylate),
      PMeO(2)MA. These new, nonacrylamide containing, cationic graft copolymers were
      prepared using atom transfer radical polymerization (ATRP) and a macroinitiator.
      They contained poly(trimethylamonium)-aminoethyl methacrylate and PMeO(2)MA,
      i.e., PTMA(+)(x)-g-(PMeO(2)MA(n))(y). They were investigated using variable
      temperature turbidity, photon correlation spectroscopy (PCS), electrophoretic
      mobility, and (1)H NMR measurements. For one system, four critical temperatures
      were measured and used to propose a mechanism for the thermally triggered changes
      that occur in solution. All of the copolymers existed as unimolecular micelles at
      20  degrees C. They underwent reversible aggregation with heating. The extent of
      aggregation was controlled by the length of the side chains. TEM showed evidence
      of micellar aggregates. The thermally responsive behaviors of our new copolymers
      are compared to those for the cationic PNIPAm graft copolymers reported by Liu et
      al. Our new cationic copolymers retained their positive charge at all
      temperatures studied, have high zeta potentials at 37  degrees C, and are good
      candidates for conferring thermoresponsiveness to negatively charged biomaterial
      surfaces.

PMID- 21967747
TI  - Implementation of checklists in health care; learning from high-reliability
      organisations.
AB  - BACKGROUND: Checklists are common in some medical fields, including surgery,
      intensive care and emergency medicine. They can be an effective tool to improve
      care processes and reduce mortality and morbidity. Despite the seemingly rapid
      acceptance and dissemination of the checklist, there are few studies describing
      the actual process of developing and implementing such tools in health care. The
      aim of this study is to explore the experiences from checklist development and
      implementation in a group of non-medical, high reliability organisations (HROs).
      METHOD: A qualitative study based on key informant interviews and field visits
      followed by a Delphi approach. Eight informants, each with 10-30 years of
      checklist experience, were recruited from six different HROs. RESULTS: The
      interviews generated 84 assertions and recommendations for checklist
      implementation. To achieve checklist acceptance and compliance, there must be a
      predefined need for which a checklist is considered a well suited solution. The
      end-users ("sharp-end") are the key stakeholders throughout the development and
      implementation process. Proximity and ownership must be assured through a
      thorough and wise process. All informants underlined the importance of short,
      self-developed, and operationally-suited checklists. Simulation is a valuable and
      widely used method for training, revision, and validation. CONCLUSION: Checklists
      have been a cornerstone of safety management in HROs for nearly a century, and
      are becoming increasingly popular in medicine. Acceptance and compliance are
      crucial for checklist implementation in health care. Experiences from HROs may
      provide valuable input to checklist implementation in healthcare.

PMID- 21967748
TI  - Effectiveness of interventions to promote healthy weight in general populations
      of children and adults: a meta-analysis.
AB  - BACKGROUND: Responding to the obesity epidemic requires robust evidence to help
      prioritize the allocation of scarce resources to preventive interventions. The
      aim of this study was to evaluate interventions that promote healthy weight
      [defined as reduction in body mass index (BMI) or percentage body fat] in general
      populations (unselected by weight) using a comprehensive meta-analysis.
      Interventions with both single and multiple components were considered. METHODS:
      Studies were first identified through well-conducted systematic reviews
      complemented by a search for single studies in five large medical databases up to
      6 November 2008. Sixty-eight controlled studies were included. For each
      intervention type and age group, all relevant studies were pooled in a random
      effects meta-analysis. RESULTS: In children, the highest reductions in mean BMI
      were achieved through promoting reduced television viewing [-0.27 kg/m(2) (95% CI
      -0.4 to -0.13 kg/m(2))]. Programmes combining physical activity, specifically
      themed or general health education and nutrition achieved a lower reduction [-0.1
      kg/m(2) (95% CI -0.17 to -0.04 kg/m(2))]. Other interventions had high
      heterogeneity or showed no statistically significant reduction in outcomes. In
      adults, single component interventions were found to reduce both outcome
      measures. Their mean percentage body fat was reduced through education by -1.22%
      (95% CI -1.92 to -0.52). CONCLUSION: The evidence for the effectiveness of
      promoting healthy weight in general populations is limited, though multi
      component interventions in schools and encouraging reduced children's television
      viewing are promising strategies. Improving the reporting of outcomes is vital,
      as imputation of inadequately reported measures may have contributed to the
      observed heterogeneity. Longer follow-up is essential for understanding policy
      relevance.

PMID- 21967743
TI  - Micro total analysis systems for cell biology and biochemical assays.

PMID- 21967749
TI  - Comparative performance evaluation of hepatitis C virus genotyping based on the
      5' untranslated region versus partial sequencing of the NS5B region of brazilian
      patients with chronic hepatitis C.
AB  - BACKGROUND: Genotyping of hepatitis C virus (HCV) has become an essential tool
      for prognosis and prediction of treatment duration. The aim of this study was to
      compare two HCV genotyping methods: reverse hybridization line probe assay (LiPA
      v.1) and partial sequencing of the NS5B region. METHODS: Plasma of 171 patients
      with chronic hepatitis C were screened using both a commercial method (LiPA HCV
      Versant, Siemens, Tarrytown, NY, USA) and different primers targeting the NS5B
      region for PCR amplification and sequencing analysis. RESULTS: Comparison of the
      HCV genotyping methods showed no difference in the classification at the genotype
      level. However, a total of 82/171 samples (47.9%) including misclassification,
      non-subtypable, discrepant and inconclusive results were not classified by LiPA
      at the subtype level but could be discriminated by NS5B sequencing. Of these
      samples, 34 samples of genotype 1a and 6 samples of genotype 1b were classified
      at the subtype level using sequencing of NS5B. CONCLUSIONS: Sequence analysis of
      NS5B for genotyping HCV provides precise genotype and subtype identification and
      an accurate epidemiological representation of circulating viral strains.

PMID- 21967750
TI  - The launch of the International Society for Children's Environmental Health and
      the Environment (ISCHE).

PMID- 21967751
TI  - Development of novel CH223191-based antagonists of the aryl hydrocarbon receptor.
AB  - Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that
      regulates genes involved in drug/xenobiotic metabolism, cell cycle progression,
      cell fate determination, immune function, and inflammatory response. Increasing
      evidence that AHR plays a role in the pathophysiology of a number of human
      disease states is driving the need for improved pharmacological tools to be used
      for understanding the in vivo impact of AHR modulation. In this study, we have
      characterized and used structure-activity relationship analyses of a newly
      synthesized library of derivatives of the potent AHR antagonist 2-methyl-2H
      pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazo-phenyl)-amide (CH223191).
      Initial screening of these compounds revealed that those bearing groups with
      strong electronegativity at the R1 position (i.e., CHD-5, CHD-11, and CHD-12)
      versus those that are more electron-poor at this position (i.e., CHD-7 and CHD-8)
      elicited the most potent AHR antagonistic properties. The ability of these
      derivatives to inhibit agonist (2,3,7,8-tetrachlorodibenzo-p-dioxin) binding,
      nuclear translocation of AHR, and agonist-induced enzyme activity also were
      determined and support the initial findings. Furthermore, CH223191, but not CHD
      5, CHD-11, or CHD-12, was found to exhibit AHR-independent proproliferative
      properties. These results contribute to our understanding of the structural
      requirements of potent AHR antagonists and the development of effective
      pharmacological tools to be used for studying the pathophysiological role of AHR.

PMID- 21967752
TI  - Electrochemical carbon nanotube filter oxidative performance as a function of
      surface chemistry.
AB  - An electrochemical carbon nanotube filter has been reported to be effective for
      the removal and electrooxidation of aqueous chemicals and microorganisms. Here,
      we investigate how carbon nanotube (CNT) chemical surface treatments including
      calcination to remove amorphous carbon, acid treatment to remove internal
      residual metal oxide, formation of surficial oxy-functional groups, and addition
      of Sb-doped SnO(2) particles affect the electrooxidative filter performance. The
      various CNT samples are characterized by scanning electron microscopy (SEM),
      thermogravimetric analysis (TGA), and X-ray photoelectron spectroscopy (XPS) and
      electrochemically evaluated by cyclic voltammetry, open circuit potential versus
      time analysis, and electrochemical impedance spectroscopy. Voltammetry results
      indicate that the near CNT surface pH is at least two units lower than the bulk
      pH. The electrooxidative performance of the various CNT samples is evaluated with
      1 mM of methyl orange (MO) in 100 mM sodium sulfate at a flow rate of 1.5 mL min(
      1). At both 2 and 3 V, the efficacy of electrochemical filtration is observed to
      be function of CNT surface chemistry. The samples with the greatest
      electrooxidation were the calcinated then HCl-treated CNTs, i.e., the CNTs with
      the most surficial sp(2)-bonded carbon, and the Sb-SnO(2)-coated CNTs, i.e., the
      CNTs with the most electrocatalytic surface area. At 3 V applied voltage, these
      CNT samples are able to oxidize 95% of the influent MO within the liquid
      residence time of <1.2 s. The broader applicability of electrochemical filtration
      is evaluated by challenging the C-CNT-HCl and C-CNT-HNO(3) networks with various
      organics including methylene blue, phenol, methanol, and formaldehyde. At 3 V
      applied voltage, both CNTs are able to degrade a fraction of all the organics
      with the extent organic degradation dependent on both CNT and organic properties.
      The C-CNT-HCl network generally had the better oxidative performance than the C
      CNT-HNO(3) network with an exception being the positively charged methylene blue.
      The extent of MO degradation, steady-state current, anode potential, effluent pH,
      and back pressure are also measured as a function of applied voltage (1-3 V) and
      CNT surface chemistry. Mass spectrometry of electrochemical CNT filter effluent
      at 2 and 3 V is utilized to evaluate plausible electrooxidation products. Energy
      consumption as compared to state-of-the-art electrodes and strategies to tailor
      the CNT surface for a specific target molecule are discussed.

PMID- 21967753
TI  - Retraction: a descriptive study of a manual therapy intervention within a
      randomised controlled trial for hamstring and lower limb injury prevention.
AB  - The journal has been informed by its publisher BioMed Central that contrary to
      the statement in this article [Wayne Hoskins, Henry Pollard, Chiropractic &
      Osteopathy 2010, 18:23], they have been advised by the authors' institution
      Macquarie University, that its Human Research Ethics Committee did not approve
      this study. Because the study was conducted without institutional ethics
      committee approval it has been retracted.

PMID- 21967754
TI  - Factors which influence the consumption of street foods and fast foods in South
      Africa--a national survey.
AB  - BACKGROUND: Very little is known about street food and fast food consumption
      patterns in South Africa despite this being a large sector of the national
      economy in terms of employment provided and sales of food. The objective of this
      study was to determine the use of street foods and fast foods purchased by South
      Africans living in different provinces and geographic areas. METHODS: A cross
      sectional survey was conducted. Structured interview-administered questionnaires
      in 11 official languages were conducted at the participants' homes. A nationally
      representative sample (n = 3287) was drawn from all ethnic groups, and provinces
      including participants 16 years and older. Logistic regression was done to
      evaluate factors impacting on fast food consumption. RESULTS: Frequent (2 >=
      times/week) street food consumption ranged from 1.8% in Northern Cape to 20.6% in
      Limpopo; frequent (2 >= times/week) fast food consumption ranged between 1.5% in
      North West Province to 14.7% in Gauteng. The highest intake of street food was in
      the medium socio-economic category (14.7%) while the highest intake of fast foods
      was in the high socio-economic category (13.2%). Overall, fruit was the most
      commonly purchased street food by all ethnic groups over the previous week
      although this practice was highest in black participants (35.8%). Purchases of
      soft drinks ranged from 4.8% in whites to 16.4% in blacks and savoury snacks from
      2.3% to 14.5% in whites and blacks, respectively. Consumption of fast foods and
      street foods were influenced by a number of socio-demographic factors including
      ownership of major home appliances. Frequent fast food consumers had a
      significantly higher dietary diversity score (4.69; p < 0.0001) while frequent
      street food consumers had a significantly lower score (3.81; p < 0.0001).
      CONCLUSIONS: A large percentage of the population purchase street foods and fast
      foods. This is of some concern when one notes the high prevalence of soft drink
      consumption in terms of its association with obesity and non-communicable
      diseases. These findings need to be taken into consideration when evaluating
      dietary patterns and nutritional adequacy of population diets.

PMID- 21967755
TI  - ACTH-induced cortisol release is related to the copy number of the C4B gene
      encoding the fourth component of complement in patients with non-functional
      adrenal incidentaloma.
AB  - OBJECTIVE: According to our previous findings, carriers of the C4B*Q0 genotype,
      which means zero or one copy of the C4B gene, which is located in the RCCX copy
      number variation region on chromosome 6, have a significantly shorter life
      expectancy and higher risk of cardiovascular disease than non-carriers. We have
      postulated that the C4B*Q0 genotype is linked to variant(s) of the neighboring
      CYP21A2 gene encoding a steroid 21-hydroxylase with altered function. DESIGN:
      Single-center, observational, retrospective study. PATIENTS: Seventy-six patients
      with non-functional, benign adrenal incidentaloma. MEASUREMENTS: Serum cortisol,
      aldosterone, 17-hydroxyprogesterone, corticosterone and ACTH levels basally and
      after ACTH-stimulation, metyrapone or dexamethasone tests were determined. C4B
      gene copy number was quantified. RESULTS: The ratio of ACTH-stimulated and
      baseline cortisol concentrations was significantly higher (P = 0.001) in the
      group of patients carrying the C4B*Q0 genotype compared to the rest of the
      patients. This difference remained significant (P = 0.004) after adjustment for
      sex and age, as well as for tumor size. A significant (P = 0.018), adjusted
      difference between carriers and non-carriers was found also for ACTH
      induced/basal aldosterone ratio. In C4B*Q0 carriers, metyrapone hardly reduced
      the serum cortisol level, while in non-carriers it induced a highly significant
      (P = 0.002) decrease. CONCLUSIONS: The C4B*Q0 genotype may be associated with
      hyperreactivity of the HPA axis (manifested as an increased responsiveness to
      ACTH-stimulation), probably through enhanced function of steroid 21-hydroxylase.
      Since hyperreactivity of the HPA axis is known to be associated with an increased
      risk of cardiovascular disease, our present findings may explain the increased
      cardiovascular morbidity and mortality of C4B*Q0 carriers.

PMID- 21967756
TI  - Quercetin 7-rhamnoside reduces porcine epidemic diarrhea virus replication via
      independent pathway of viral induced reactive oxygen species.
AB  - BACKGROUND: On the base of our previous study we were observed relevant studies
      on the hypothesis that the antiviral activity of quercetin 7-rhamnoside (Q7R), a
      flavonoid, won't relate ability of its antioxidant. METHODS: We were investigated
      the effects of Q7R on the cytopathic effects (CPE) by CPE reduction assay.
      Production of DNA fragment and reactive oxygen species (ROS) induced by PEDV
      infection were studied using DNA fragmentation assay and flow cytometry. RESULTS:
      In the course of this study it was discovered that Q7R is an extremely potent
      compound against PEDV. The addition of Q7R to PEDV-infected Vero cells directly
      reduced the formation of a visible cytopathic effect (CPE). Also, Q7R did not
      induce DNA fragmentation. Furthermore, ROS increased the infection of PEDV, which
      was strongly decreased by N-acetyl-L-cysteins (NAC). However, the increased ROS
      was not decreased by Q7R. Antiviral activity of antioxidants such as NAC,
      pyrrolidine dithiocarbamate (PDTC), and the vitamin E derivative, trolox, were
      hardly noticed. CONCLUSIONS: We concluded that the inhibition of PEDV production
      by Q7R is not simply due to a general action as an antioxidants and is highly
      specific, as several other antioxidants (NAC, PDTC, trolox) are inactive against
      PEDV infection.

PMID- 21967757
TI  - Facing up to programmatic challenges created by the HIV/AIDS epidemic in sub
      Saharan Africa.
AB  - Three decades after the emergence of HIV, we have made great strides in our
      response to the epidemic, from prevention of transmission to testing and
      treatment. However, it is still common in high-prevalence settings for people to
      not know their HIV status, and estimates are that globally, a mere 36% of those
      eligible for treatment are receiving it. On top of this, for every person with
      HIV entering treatment, two more are infected. The operational obstacles to
      overcoming the challenges and fully implementing proven strategies are numerous.
      The operational research and implementation sciences aim to provide a sound basis
      for how to maximize the use of limited resources by investigating the best models
      to deliver services and implement programmes in various settings and contexts. In
      this special issue, the Journal of the International AIDS Society intends to
      highlight some of the operational and programmatic challenges that are faced in
      sub-Saharan Africa, home to the largest population living with HIV. Our hope is
      that readers gain insight into some of the challenges associated with the
      HIV/AIDS epidemic and a changing environment in the region, and become familiar
      with some applications of operational research and implementation science in HIV
      healthcare settings.

PMID- 21967758
TI  - The challenge facing translation of basic science into clinical and community
      settings to improve health outcomes.

PMID- 21967759
TI  - Collagen intermingled chitosan-tripolyphosphate nano/micro fibrous scaffolds for
      tissue-engineering application.
AB  - Scaffolds comprising a nano- and micro-fibrous architecture are promising for
      tissue engineering, where nanofibers act as connecting network among microfibers
      and provide a 3D structural environment and mechanical stability for facilitating
      cell attachment, proliferation and migration. In this study, a novel structure
      was developed with polymeric micro and nano combined fibrous architecture, which
      aims to mimic the native extracellular matrix for tissue regeneration. Chitosan
      tripolyphosphate (TPP) microfibers were prepared by wet spinning method, where
      collagen solution was allowed to self-assemble into nano/microfibers and
      subsequently freeze-dried for obtaining this combined architecture. To ensure
      prolonged mechanical stability, the scaffold was cross-linked using 1-ethyl-3-(3
      dimethyl aminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). This
      polymeric nano/micro combined scaffold revealed remarkable cellular activity and
      cytocompatibility towards both fibroblasts and osteoblast like cells and
      supported improved attachment and proliferation of cells than that of bare
      chitosan-TPP scaffolds owing to the presence of a bioactive molecule, collagen,
      in the intermingled form with chitosan-TPP microfiber. 

PMID- 21967760
TI  - ProfileChaser: searching microarray repositories based on genome-wide patterns of
      differential expression.
AB  - SUMMARY: We introduce ProfileChaser, a web server that allows for querying the
      Gene Expression Omnibus based on genome-wide patterns of differential expression.
      Using a novel, content-based approach, ProfileChaser retrieves expression
      profiles that match the differentially regulated transcriptional programs in a
      user-supplied experiment. This analysis identifies statistical links to similar
      expression experiments from the vast array of publicly available data on
      diseases, drugs, phenotypes and other experimental conditions. AVAILABILITY:
      http://profilechaser.stanford.edu CONTACT: abutte@stanford.edu SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 21967761
TI  - MDpocket: open-source cavity detection and characterization on molecular dynamics
      trajectories.
AB  - MOTIVATION: A variety of pocket detection algorithms are now freely or
      commercially available to the scientific community for the analysis of static
      protein structures. However, since proteins are dynamic entities, enhancing the
      capabilities of these programs for the straightforward detection and
      characterization of cavities taking into account protein conformational ensembles
      should be valuable for capturing the plasticity of pockets, and therefore allow
      gaining insight into structure-function relationships. RESULTS: This article
      describes a new method, called MDpocket, providing a fast, free and open-source
      tool for tracking small molecule binding sites and gas migration pathways on
      molecular dynamics (MDs) trajectories or other conformational ensembles. MDpocket
      is based on the fpocket cavity detection algorithm and a valuable contribution to
      existing analysis tools. The capabilities of MDpocket are illustrated for three
      relevant cases: (i) the detection of transient subpockets using an ensemble of
      crystal structures of HSP90; (ii) the detection of known xenon binding sites and
      migration pathways in myoglobin; and (iii) the identification of suitable pockets
      for molecular docking in P38 Map kinase. AVAILABILITY: MDpocket is free and open
      source software and can be downloaded at http://fpocket.sourceforge.net. CONTACT:
      pschmidtke@ub.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at
      Bioinformatics online.

PMID- 21967762
TI  - Improving the detection of transmembrane beta-barrel chains with N-to-1 extreme
      learning machines.
AB  - MOTIVATION: Transmembrane beta-barrels (TMBBs) are extremely important proteins
      that play key roles in several cell functions. They cross the lipid bilayer with
      beta-barrel structures. TMBBs are presently found in the outer membranes of Gram
      negative bacteria and of mitochondria and chloroplasts. Loop exposure outside the
      bacterial cell membranes makes TMBBs important targets for vaccine or drug
      therapies. In genomes, they are not highly represented and are difficult to
      identify with experimental approaches. Several computational methods have been
      developed to discriminate TMBBs from other types of proteins. However, the best
      performing approaches have a high fraction of false positive predictions.
      RESULTS: In this article, we introduce a new machine learning approach for TMBB
      detection based on N-to-1 Extreme Learning Machines that significantly
      outperforms previous methods achieving a Matthews correlation coefficient of
      0.82, a probability of correct prediction of 0.92 and a sensitivity of 0.73.

PMID- 21967763
TI  - Groundwater or floodwater? Assessing the pathways of metal exports from a coastal
      acid sulfate soil catchment.
AB  - Daily observations of dissolved aluminum, iron, and manganese in an estuary
      downstream of a coastal acid sulfate soil (CASS) catchment provided insights into
      how floods and submarine groundwater discharge drive wetland metal exports.
      Extremely high Al, Fe, and Mn concentrations (up to 40, 374, and 8 mg L(-1),
      respectively) were found in shallow acidic groundwaters from the Tuckean Swamp,
      Australia. Significant correlations between radon (a natural groundwater tracer)
      and metals in surface waters revealed that metal loads were driven primarily by
      groundwater discharge. Dissolved Fe, Mn, and Al loads during a 16-day flood
      triggered by a 213 mm rain event were respectively 80, 35, and 14% of the total
      surface water exports during the four months of observations. Counter clockwise
      hysteresis was observed for Fe and Mn in surface waters during the flood due to
      delayed groundwater inputs. Groundwater-derived Fe fluxes into artificial drains
      were 1 order of magnitude higher than total surface water exports, which is
      consistent with the known accumulation of monosulfidic black ooze within the
      wetland drains. Upscaling the Tuckean catchment export estimates yielded
      dissolved Fe fluxes from global acid sulfate soil catchments on the same order of
      magnitude of global river inputs into estuaries.

PMID- 21967764
TI  - Considerations on BVD eradication for the Irish livestock industry.
AB  - Animal Health Ireland has produced clear guidelines for the control of Bovine
      Viral Diarrhoea (BVD) infection in Irish cattle herds. In the course of
      developing these guidelines it was clear that a framework for regional and/or
      national BVD control would be required to increase the uptake of BVD control at
      farm level and reduce the overall prevalence of the disease. This paper assessed
      the economic impact of BVD, epidemiological aspects of the disease to its
      control, models of BVD control, international experiences of BVD control
      programmes. The technical knowledge and test technology exists to eradicate BVD.
      Indeed, many countries have successfully and others are embarking on control of
      the disease. The identification and prompt elimination of PI cattle will form the
      basis of any control programme. The trade of such animals must be curtailed.
      Pregnant and potentially pregnant carrying PI foetuses pose a significant threat.
      International experience indicates systematic, well coordinated programmes have
      the most success, while voluntary programmes can make good initial progress but
      ultimately fail. The farming community must buy into any proposed programme, and
      without their support, failure is likely. To buy into the programme and create
      such a demand for BVD control, farmers must first be well informed. It is likely
      that stemming economic loss and improving productivity will be the primary
      motivator at individual farm level.

PMID- 21967765
TI  - Ohtahara syndrome with emphasis on recent genetic discovery.
AB  - Ohtahara syndrome or Early Infantile Epileptic Encephalopathy (EIEE) with
      Suppression-Burst, is the most severe and the earliest developing age-related
      epileptic encephalopathy. Clinically, the syndrome is characterized by early
      onset tonic spasms associated with a severe and continuous pattern of burst
      activity. It is a debilitating and early progressive neurological disorder,
      resulting in intractable seizures and severe mental retardation. Specific
      mutations in at least four genes (whose protein products are essential in lower
      brain's neuronal and interneuronal functions, including mitochondrial respiratory
      chains have been identified in unrelated individuals with EIEE and include: (a)
      the ARX (aristaless-related) homeobox gene at Xp22.13 (EIEE-1 variant); (b) the
      CDKL5 (SYK9) gene at Xp22 (EIEE-2 variant); (c) the SLC25A22 (GC1) gene at
      11p15.5 (EIEE-3 variant); and (d) the Stxbp1 (MUNC18-1) gene at 9q34-1 (EIEE-4
      variant). A yet unresolved issue involves the relationship between early
      myoclonic encephalopathy (EME-ErbB4 mutations) versus the EIEE spectrum of
      disorders.

PMID- 21967766
TI  - Regulation of neutrophils by interferon-gamma limits lung inflammation during
      tuberculosis infection.
AB  - Resistance to Mycobacterium tuberculosis requires the host to restrict bacterial
      replication while preventing an over-exuberant inflammatory response. Interferon
      (IFN) gamma is crucial for activating macrophages and also regulates tissue
      inflammation. We dissociate these two functions and show that IFN-gamma(-/-)
      memory CD4(+) T cells retain their antimicrobial activity but are unable to
      suppress inflammation. IFN-gamma inhibits CD4(+) T cell production of IL-17,
      which regulates neutrophil recruitment. In addition, IFN-gamma directly inhibits
      pathogenic neutrophil accumulation in the infected lung and impairs neutrophil
      survival. Regulation of neutrophils is important because their accumulation is
      detrimental to the host. We suggest that neutrophilia during tuberculosis
      indicates failed Th1 immunity or loss of IFN-gamma responsiveness. These results
      establish an important antiinflammatory role for IFN-gamma in host protection
      against tuberculosis.

PMID- 21967767
TI  - Transcytosis of Listeria monocytogenes across the intestinal barrier upon
      specific targeting of goblet cell accessible E-cadherin.
AB  - Listeria monocytogenes (Lm) is a foodborne pathogen that crosses the intestinal
      barrier upon interaction between its surface protein InlA and its species
      specific host receptor E-cadherin (Ecad). Ecad, the key constituent of adherens
      junctions, is typically situated below tight junctions and therefore considered
      inaccessible from the intestinal lumen. In this study, we investigated how Lm
      specifically targets its receptor on intestinal villi and crosses the intestinal
      epithelium to disseminate systemically. We demonstrate that Ecad is luminally
      accessible around mucus-expelling goblet cells (GCs), around extruding
      enterocytes at the tip and lateral sides of villi, and in villus epithelial
      folds. We show that upon preferential adherence to accessible Ecad on GCs, Lm is
      internalized, rapidly transcytosed across the intestinal epithelium, and released
      in the lamina propria by exocytosis from where it disseminates systemically.
      Together, these results show that Lm exploits intrinsic tissue heterogeneity to
      access its receptor and reveal transcytosis as a novel and unanticipated pathway
      that is hijacked by Lm to breach the intestinal epithelium and cause systemic
      infection.

PMID- 21967768
TI  - Critical role of the neutrophil-associated high-affinity receptor for IgE in the
      pathogenesis of experimental cerebral malaria.
AB  - The role of the IgE-FcepsilonRI complex in malaria severity in Plasmodium
      falciparum-hosting patients is unknown. We demonstrate that mice genetically
      deficient for the high-affinity receptor for IgE (FcepsilonRIalpha-KO) or for IgE
      (IgE-KO) are less susceptible to experimental cerebral malaria (ECM) after
      infection with Plasmodium berghei (PbANKA). Mast cells and basophils, which are
      the classical IgE-expressing effector cells, are not involved in disease as mast
      cell-deficient and basophil-depleted mice developed a disease similar to wild
      type mice. However, we show the emergence of an FcepsilonRI(+) neutrophil
      population, which is not observed in mice hosting a non-ECM-inducing PbNK65
      parasite strain. Depletion of this FcepsilonRI(+) neutrophil population prevents
      ECM, whereas transfer of this population into FcepsilonRIalpha-KO mice restores
      ECM susceptibility. FcepsilonRI(+) neutrophils preferentially home to the brain
      and induce elevated levels of proinflammatory cytokines. These data define a new
      pathogenic mechanism of ECM and implicate an FcepsilonRI-expressing neutrophil
      subpopulation in malaria disease severity.

PMID- 21967769
TI  - XRCC1 suppresses somatic hypermutation and promotes alternative nonhomologous end
      joining in Igh genes.
AB  - Activation-induced deaminase (AID) deaminates cytosine to uracil in
      immunoglobulin genes. Uracils in DNA can be recognized by uracil DNA glycosylase
      and abasic endonuclease to produce single-strand breaks. The breaks are repaired
      either faithfully by DNA base excision repair (BER) or mutagenically to produce
      somatic hypermutation (SHM) and class switch recombination (CSR). To unravel the
      interplay between repair and mutagenesis, we decreased the level of x-ray cross
      complementing 1 (XRCC1), a scaffold protein involved in BER. Mice heterozygous
      for XRCC1 showed a significant increase in the frequencies of SHM in Igh variable
      regions in Peyer's patch cells, and of double-strand breaks in the switch regions
      during CSR. Although the frequency of CSR was normal in Xrcc1(+/-) splenic B
      cells, the length of microhomology at the switch junctions decreased, suggesting
      that XRCC1 also participates in alternative nonhomologous end joining.
      Furthermore, Xrcc1(+/-) B cells had reduced Igh/c-myc translocations during CSR,
      supporting a role for XRCC1 in microhomology-mediated joining. Our results imply
      that AID-induced single-strand breaks in Igh variable and switch regions become
      substrates simultaneously for BER and mutagenesis pathways.

PMID- 21967771
TI  - Upregulation of Polymeric Immunoglobulin Receptor Expression by the Heat
      Inactivated Potential Probiotic Bifidobacterium bifidum OLB6378 in a Mouse
      Intestinal Explant Model.
AB  - We determined whether a potential probiotic bacterium, Bifidobacterium bifidum
      OLB6378 (BB6378), exerts beneficial effects on the mucosal immune system in a
      mouse intestinal explant model. The addition of heat-inactivated BB6378 to
      intestinal explants prepared from embryonic day 18 BALB/c mice increased the
      expression of polymeric immunoglobulin receptor (pIgR) mRNA by two- to fivefold.
      These effects were observed on ileal and colonic explants but not on jejunal
      explants, suggesting that the BB6378-induced pIgR upregulation is site-specific
      within the mouse intestine. The upregulation of pIgR protein expression in
      colonic explants was also detected after 24 h of culture. The results of DNA
      microarray analysis of ileal and colonic samples indicated that BB6378 increased
      the gene expression of interleukin (IL)-1alpha and IL-1beta, and IL-1alpha
      content in colonic explants was significantly increased after 20 h of culture
      with BB6378. We then examined the involvement of endogenously induced IL-1alpha
      in pIgR mRNA upregulation by using IL-1alpha knockout (KO) mice. Contrary to our
      expectations, pIgR mRNA expression was equally upregulated by BB6378 in colonic
      explants from BALB/c and IL-1alpha KO mice. Conversely, we examined the
      involvement of Toll-like receptors in pIgR mRNA upregulation by using MyD88 KO
      mice. The upregulation of pIgR was completely suppressed in the explants derived
      from MyD88 KO mice. Taken together, we conclude that in a mouse intestinal
      explant model, the heat-inactivated potential probiotic BB6378 increases
      intestinal pIgR expression in a site-specific manner and that the upregulation of
      pIgR could be explained by a direct microbial effect on the epithelium via Toll
      like receptors.

PMID- 21967770
TI  - Quantification of compensatory processes of postnatal hypoxia in newborn piglets
      applying short-term nonlinear dynamics analysis.
AB  - BACKGROUND: Newborn mammals suffering from moderate hypoxia during or after birth
      are able to compensate a transitory lack of oxygen by adapting their vital
      functions. Exposure to hypoxia leads to an increase in the sympathetic tone
      causing cardio-respiratory response, peripheral vasoconstriction and
      vasodilatation in privileged organs like the heart and brain. However, there is
      only limited information available about the time and intensity changes of the
      underlying complex processes controlled by the autonomic nervous system. METHODS:
      In this study an animal model involving seven piglets was used to examine an
      induced state of circulatory redistribution caused by moderate oxygen deficit. In
      addition to the main focus on the complex dynamics occurring during sustained
      normocapnic hypoxia, the development of autonomic regulation after induced
      reoxygenation had been analysed. For this purpose, we first introduced a new
      algorithm to prove stationary conditions in short-term time series. Then we
      investigated a multitude of indices from heart rate and blood pressure
      variability and from bivariate interactions, also analysing respiration signals,
      to quantify the complexity of vegetative oscillations influenced by hypoxia.
      RESULTS: The results demonstrated that normocapnic hypoxia causes an initial
      increase in cardiovascular complexity and variability, which decreases during
      moderate hypoxia lasting one hour (p < 0.004). After reoxygenation,
      cardiovascular complexity parameters returned to pre-hypoxic values (p < 0.003),
      however not respiratory-related complexity parameters. CONCLUSIONS: In
      conclusion, indices from linear and nonlinear dynamics reflect considerable
      temporal changes of complexity in autonomous cardio-respiratory regulation due to
      normocapnic hypoxia shortly after birth. These findings might be suitable for non
      invasive clinical monitoring of hypoxia-induced changes of autonomic regulation
      in newborn humans.

PMID- 21967772
TI  - Improved sub-areolar breast tissue removal in nipple-sparing mastectomy using
      hydrodissection.
AB  - We report on a new technique of dissection of the nipple-areola-complex (NAC) in
      nipple-sparing mastectomy (NSM). NACs removed due to the presence of tumor cells
      beneath them were histologically examined for the presence of normal breast
      glandular tissue. Cases were divided into cohort 1, where NACs were dissected by
      sharp isolation, coring the nipple, and cohort 2, where the same procedure was
      preceded by hydrodissection of the areola. In 20 (17.4%) cases the planned NSM
      was converted to skin-sparing mastectomy (SSM) because of intraoperative findings
      of cancer in retro-areolar tissue. Histological examination of 20 NSMs converted
      to SSM showed the presence of glandular tissue in 12 out of 13 cohort 1 cases
      (92%) and in 1 out of 7 cohort 2 cases (14%). We conclude that hydrodissection
      creates a subdermal plane facilitating NAC dissection and permitting a more
      complete removal of breast tissue in NSM. Such radicality could prove important
      in the treatment of breast cancer and in BRCA 1-2 mutation carriers because of
      its potential for reducing the risk of relapse.

PMID- 21967773
TI  - Lipid metabolism and body composition in Gclm(-/-) mice.
AB  - In humans and experimental animals, high fat diets (HFD) are associated with risk
      factors for metabolic diseases, such as excessive weight gain and adiposity,
      insulin resistance and fatty liver. Mice lacking the glutamate-cysteine ligase
      modifier subunit gene (Gclm(-/-)) and deficient in glutathione (GSH), are
      resistant to HFD-mediated weight gain. Herein, we evaluated Gclm-associated
      regulation of energy metabolism, oxidative stress, and glucose and lipid
      homeostasis. C57BL/6J Gclm(-/-) mice and littermate wild-type (WT) controls
      received a normal diet or an HFD for 11 weeks. HFD-fed Gclm(-/-) mice did not
      display a decreased respiratory quotient, suggesting that they are unable to
      process lipid for metabolism. Although dietary energy consumption and intestinal
      lipid absorption were unchanged in Gclm(-/-) mice, feeding these mice an HFD did
      not produce excess body weight nor fat storage. Gclm(-/-) mice displayed higher
      basal metabolic rates resulting from higher activities of liver mitochondrial
      NADH-CoQ oxidoreductase, thus elevating respiration. Although Gclm(-/-) mice
      exhibited strong systemic and hepatic oxidative stress responses, HFD did not
      promote glucose intolerance or insulin resistance. Furthermore, HFD-fed Gclm(-/-)
      mice did not develop fatty liver, likely resulting from very low expression
      levels of genes encoding lipid metabolizing enzymes. We conclude that Gclm is
      involved in the regulation of basal metabolic rate and the metabolism of dietary
      lipid. Although Gclm(-/-) mice display a strong oxidative stress response, they
      are protected from HFD-induced excessive weight gain and adipose deposition,
      insulin resistance and steatosis.

PMID- 21967776
TI  - Laparoscopic single-incision repair of internal hernia defects using an
      intracorporeal suturing technique.

PMID- 21967774
TI  - Glutathione enzyme and selenoprotein polymorphisms associate with mercury
      biomarker levels in Michigan dental professionals.
AB  - Mercury is a potent toxicant of concern to both the general public and
      occupationally exposed workers (e.g., dentists). Recent studies suggest that
      several genes mediating the toxicokinetics of mercury are polymorphic in humans
      and may influence inter-individual variability in mercury accumulation. This work
      hypothesizes that polymorphisms in key glutathione synthesizing enzyme,
      glutathione S-transferase, and selenoprotein genes underlie inter-individual
      differences in mercury body burden as assessed by analytical mercury measurement
      in urine and hair, biomarkers of elemental mercury and methylmercury,
      respectively. Urine and hair samples were collected from a population of dental
      professionals (n=515), and total mercury content was measured. Average urine
      (1.06+/-1.24 microg/L) and hair mercury levels (0.49+/-0.63 microg/g) were
      similar to national U.S. population averages. Taqman assays were used to genotype
      DNA from buccal swab samples at 15 polymorphic sites in genes implicated in
      mercury metabolism. Linear regression modeling assessed the ability of
      polymorphisms to modify the relationship between mercury biomarker levels and
      exposure sources (e.g., amalgams, fish consumption). Five polymorphisms were
      significantly associated with urine mercury levels (GSTT1 deletion), hair mercury
      levels (GSTP1-105, GSTP1-114, GSS 5'), or both (SEPP1 3'UTR). Overall, this study
      suggests that polymorphisms in selenoproteins and glutathione-related genes may
      influence elimination of mercury in the urine and hair or mercury retention
      following exposures to elemental mercury (via dental amalgams) and methylmercury
      (via fish consumption).

PMID- 21967775
TI  - Serum creatinine measurement immediately after cardiac surgery and prediction of
      acute kidney injury.
AB  - BACKGROUND: After heart surgery, acute kidney injury (AKI) confers substantial
      long-term risk of death and chronic kidney disease. We hypothesized that small
      changes in serum creatinine (SCr) levels measured within a few hours of exit from
      the operating room could help discriminate those at low versus high risk of AKI.
      STUDY DESIGN: Prospective cohort of 350 elective cardiac surgery patients (valve
      or coronary artery bypass grafting) recruited in Winnipeg, Canada. Baseline SCr
      level was obtained at the preoperative visit 2 weeks before surgery. The
      postoperative SCr level was drawn within 6 hours of completion of surgery and
      then daily while the patient was in the hospital. PREDICTOR: Immediate (ie, <6
      hours) postoperative SCr level change (DeltaSCr), categorized as within 10%
      (reference), decrease >10%, or increase >10% relative to baseline. OUTCOME: AKI,
      defined according to the new KDIGO (Kidney Disease: Improving Global Outcomes)
      consensus definition as an increase in SCr level >0.3 mg/dL within 48 hours or
      >1.5 times baseline within 1 week. MEASUREMENTS: We compared the C statistic of
      logistic models with and without inclusion of immediate postoperative DeltaSCr.
      RESULTS: After surgery, 176 patients (52%) experienced a decrease >10% in SCr
      level, 26 (7.4%) experienced an increase >10%, and 143 had DeltaSCr within +/-10%
      of baseline. During hospitalization, 53 (14%) developed AKI. Bypass pump time,
      baseline estimated glomerular filtration rate, and European System for Cardiac
      Operative Risk Evaluation (euroSCORE) were associated with AKI in a parsimonious
      base logistic model. Added to the base model, immediate postoperative DeltaSCr
      was associated strongly with subsequent AKI and significantly improved model
      discrimination over the base model (C statistic, 0.78 [95% CI, 0.71-0.85] vs 0.69
      [95% CI, 0.62-0.77]; P < 0.001). A >=10% SCr level decrease predicted
      significantly lower AKI risk (OR, 0.37; 95% CI, 0.18-0.76), whereas a >=10% SCr
      level increase predicted significantly higher (OR, 6.38; 95% CI, 2.37-17.2) AKI
      risk compared with the reference category. LIMITATIONS: We used a surrogate
      marker of AKI. External validation of our results is warranted. CONCLUSION: In
      elective cardiac surgery patients, measurement of immediate postoperative
      DeltaSCr improves prediction of AKI.

PMID- 21967777
TI  - Gastric band removal and conversion to sleeve gastrectomy for vasovagal syncopal
      episodes associated with adjustable gastric banding placed using pars flaccida
      technique.

PMID- 21967778
TI  - Financial aspects, or how to use a robot assistance without losing money.
      Perspectives from private practice.

PMID- 21967779
TI  - Location of robotic surgical systems worldwide and in France.
AB  - The advent of robot-assisted surgery is a surgical revolution. However, the costs
      of installing and using a da Vinci system are impediments to the proliferation of
      this technology. This article reviews the locations of robotic surgical systems
      worldwide and in France, in 2010.

PMID- 21967780
TI  - A 90-day toxicology study of high-amylose transgenic rice grain in Sprague-Dawley
      rats.
AB  - A transgenic rice line (TRS) with high amylose level has been developed by
      antisense RNA inhibition of starch branching enzymes. Compositional analysis of
      TRS demonstrated that the content of resistant starch (RS) was significantly
      higher compared to conventional non-transgenic rice. High level of RS is an
      important raw material in food industry and has various physiological effects for
      human health. In order to provide the reliable theory basis for field release of
      TRS rice, we evaluated the potential health effects of long-term consumption of
      the TRS. The 90-day toxicology feeding experiment was conducted in Sprague-Dawley
      rats fed with diets containing 70% of either TRS rice flour, its near-isogenic
      rice flour or the control diet. The clinical performance variables (body weight,
      body weight gain and food consumption) were measured and pathological responses
      (hematological parameters and serum chemistry at the midterm and the completion
      of the experiment, urinalysis profile and serum sex hormone response at the
      completion of the experiment) were performed. Besides, clinical signs, relative
      organ weights and microscopic observations were also compared between TRS group
      and its near-isogenic rice group. The combined data indicates that high-amylose
      TRS grain is as safe as the conventional non-transgenic rice for rat consumption.

PMID- 21967781
TI  - Catechin hydrate inhibits proliferation and mediates apoptosis of SiHa human
      cervical cancer cells.
AB  - Catechin hydrate (CH), one of the chemical compounds in green tea, has been shown
      to inhibit tumor growth. Green tea possesses anticancer potential and is one of
      the most commonly used herbal medicines worldwide. In this study, we sought to
      characterize the DNA damage and downstream genes targeted by CH extracts using
      SiHa human cervical cancer cells. The efficacy of CH in killing cervical cancer
      cells in vitro was investigated in this study to determine whether CH possesses
      anticancer potential and could be developed as a therapeutic agent for cervical
      cancer upon further investigation. To scientifically validate the anticancer
      activities of CH on cervical cancer, CH was tested for its cytotoxic and growth
      inhibition properties, specifically the induction of apoptosis in SiHa cervical
      cancer cells. CH showed a 50% inhibition of SiHa human cervical cancer cells at a
      concentration of 196.07 MUg/mL at 24h. CH induced the several folds increase of
      caspase-3, -8, and -9 after 24h and 48 h; the increase of these genes may be
      involved in the induction of apoptosis. The analysis of apoptosis by DeadEnd
      terminal transferase-mediated dUTP-digoxigenin-end labeling (TUNEL) assay was
      used to further confirm that CH induced apoptosis. The results suggested that CH
      has the potential to benefit cervical cancer prevention. This is the first report
      that shows the possible mechanism of the anti-proliferative effects of CH in the
      prevention of cervical cancer in cell culture models. CH, either in its original
      form or in combination with other anticancer drugs, could potentially be an
      alternative medicine for cervical cancer. Further study may increase our
      understanding of the mechanism by which CH has an effect on cervical cancer
      therapy.

PMID- 21967782
TI  - Dietary lipids modulate methylmercury toxicity in Atlantic salmon.
AB  - This experiment aimed to study the molecular toxicity of methylmercury (MeHg) in
      liver, brain and white muscle of Atlantic salmon fed a diet based on fish oil
      (FO, high dietary n-3/n-6 ratio) compared to an alternative diet mainly based on
      vegetable oil (VO, low dietary n-3/n-6 ratio). Juvenile salmon were fed
      decontaminated diets or the FO and VO diets enriched with 5 mg Hg/kg (added as
      MeHg) for three months. The dietary lipid composition affected the fatty acid
      composition in the tissues, especially in liver and white muscle. After 84 days
      of exposure, the liver accumulated three times as much MeHg as the brain and
      white muscle. Vitamin C content and heme oxygenase, tubulin alpha (TUBA) and Cpt1
      transcriptional levels all showed significant effects of MeHg exposure in the
      liver. TBARS, alpha-tocopherol, gamma-tocopherol, and the transcriptional levels
      of thioredoxin, heme oxygenase, TUBA, PPARB1, D5D and D6D showed an effect of
      dietary lipid composition in liver tissue. Effects of dietary lipids were
      observed in brain tissue for MT-A, HIF1, Bcl-X and TUBA. Interaction effects
      between MeHg exposure and dietary lipid composition were observed in all tissues.
      Our data suggest that dietary fats have modulating effects on MeHg toxicity in
      Atlantic salmon.

PMID- 21967784
TI  - Supermatrices, supertrees and serendipitous scaffolding: inferring a well
      resolved, genus-level phylogeny of Styphelioideae (Ericaceae) despite missing
      data.
AB  - For the predominantly southern hemisphere plant group Styphelioideae (Ericaceae)
      published sequence datasets of five markers are now available for all except one
      of the 38 recognised genera. However, several markers are highly incomplete
      therefore missing data is problematic for producing a genus level phylogeny. We
      explore the relative utility of supertree and supermatrix approaches for
      addressing this challenge, and examine the effects of missing data on tree
      topology and resolution. Although the supertree approach returned a more
      conservative hypothesis, overall, both supermatrix and supertree analyses
      concurred in the topologies they returned. Using multiple genes and a dataset of
      variably complete taxa we found improved support for the monophyly and position
      of the tribes and genus level relationships. However, there was mixed support for
      the Richeeae tribe appearing one node basal to the Cosmelieae tribe or vice
      versa. It is probable that this will only be resolved through further sequencing.
      Our study supports previous findings that the amount of data is more critical
      than the completeness of the dataset in estimating well-resolved trees. Our
      results suggest that a "serendipitous" scaffolding approach that includes a
      mixture of well and poorly sequenced taxa can lead to robust phylogenetic
      hypotheses.

PMID- 21967783
TI  - Adult mortality in the cities of Bulawayo and Harare, Zimbabwe: 1979-2008.
AB  - BACKGROUND: Zimbabwe has been severely affected by the HIV/AIDS and tuberculosis
      epidemics, with an estimated 80% of tuberculosis patients being HIV infected. We
      set out to use annual population-mortality records from the cities of Harare and
      Bulawayo to describe trends and possible causes of mortality from 1979 to 2008.
      The specific objectives were to document overall, sex and age-specific mortality,
      proportion of deaths attributed to AIDS and tuberculosis, and changes in death
      rates since the start of antiretroviral therapy in 2004. METHODS: This
      retrospective descriptive study used existing mortality records of the Health
      Services departments in Harare and Bulawayo. Data points included: estimated
      yearly total population; groupings by sex and age; deaths (total and by sex and
      age groups for each year of the study period); and most frequently reported
      causes of death (for age groups <15 years, 15-44 years and >= 45 years). Data on
      deaths were aggregated by year, and crude, sex- and age-specific death rates were
      calculated per 1000 population. Tuberculosis and HIV-related disease-specific
      death rates and proportion of deaths attributed to these conditions were
      computed. RESULTS: In both cities, crude death rates were lowest in the late
      1980s, increased three- to five-fold by the early 2000s, and began a slow and, in
      the case of Bulawayo, intermittent decline from 2004. Sex-specific death rates
      followed a similar trend, being higher in males than in females. The death rates
      in the age groups <5 years, 15-44 years and >= 45 years showed significant
      increases, with a gradual levelling off and decline from 2002 onwards; death
      rates in those aged 5-14 years were relatively unaffected. Tuberculosis and HIV
      caused 70% of deaths in the age group of 15-44 years from the early 1990 s.
      CONCLUSIONS: This study used routinely collected population-mortality data that
      are rare in resource-limited settings, and it described, for the first time in
      Zimbabwe, the effects of the HIV/AIDS epidemic and the introduction of
      antiretroviral therapy on death rates in two large cities. After a substantial
      rise in crude mortality rates, there has been a decline associated with the
      introduction of ART. Such routine population data must continue to be collected,
      collated and analyzed.

PMID- 21967785
TI  - Phylogenetic relationships of the algae scraping cyprinid genus Capoeta
      (Teleostei: Cyprinidae).
AB  - We reconstructed the matrilineal phylogeny of Asian algae-eating fishes of the
      genus Capoeta based on complete mitochondrial gene for cytochrome b sequences
      obtained from 20 species sampled from the majority of the range and 44 species of
      closely related barbs of the genera Barbus s. str. and Luciobarbus. The results
      of this study show that Capoeta forms a strongly supported monophyletic subclade
      nested within the Luciobarbus clade, suggesting that specialized scraping
      morphology appeared once in the evolutionary history of the genus. We detected
      three main groups of Capoeta: the Mesopotamian group, which includes three
      species from the Tigris-Euphrates system and adjacent water bodies, the Anatolian
      Iranian group, which has the most diversified structure and encompasses many
      species distributed throughout Anatolian and Iranian inland waters, and the Aralo
      Caspian group, which consists of species distributed in basins of the Caspian and
      Aral Seas, including many dead-end rivers in Central Asia and Northern Iran. The
      most probable origination pathway of the genus Capoeta is hypothesized to occur
      as a result of allopolyploidization. The origin of Capoeta was found around the
      Langhian-Serravallian boundary according to our molecular clock. The
      diversification within the genus occurred along Middle Miocene-Late Pliocene
      periods.

PMID- 21967786
TI  - Template directed formation of nanoparticle decorated multi-walled carbon
      nanotube bundles with uniform diameter.
AB  - Bundles of multi-walled carbon nanotubes of uniform diameter decorated with Ni
      nanoparticles were synthesized using mesoporous silicates as templates. The
      ordered morphology and the narrow pore size distribution of mesoporous silicates
      provide an ideal platform to synthesize uniformly sized carbon nanotubes. In
      addition, homogeneous sub-10 nm pore sizes of the templates allow in situ
      formation of catalytic nanoparticles with uniform diameters which end up
      decorating the carbon nanotubes. The resulting carbon nanotubes are multi-walled
      with a uniform diameter corresponding to the pore diameter of the template used
      during the synthesis that are decorated with the catalysts used to synthesize
      them. They have a narrow size distribution which can be used in many energy
      related fields of research.

PMID- 21967787
TI  - Clinical outcome of B2/C type isolated proximal LAD disease treated with drug
      eluting stents.

PMID- 21967788
TI  - Cardiac hydatid cyst case recovered with medical treatment.

PMID- 21967789
TI  - Native mitral valve causing left ventricular outflow tract obstruction in an
      adult with Ebstein's anomaly.

PMID- 21967790
TI  - Dental volumetric tomography in the radiological detection of carotid artery
      calcification.

PMID- 21967791
TI  - Maternal cardiovascular hemodynamics in a patient with mitral prosthetic heart
      valve evaluated with impedance cardiography and echocardiography.

PMID- 21967792
TI  - Two-year results of primary coronary intervention performed in a medium-scale
      primary percutaneous coronary intervention center by two cardiologists who are
      not formally trained in interventional cardiology.

PMID- 21967793
TI  - Cor triatriatum sinister with secundum atrial septal defect in a patient with
      recurrent pulmonary infections.

PMID- 21967794
TI  - Libman-Sacks endocarditis mimicking cardiac myxoma.

PMID- 21967795
TI  - Double-chambered right ventricle associated with ventricular septal defect and
      subaortic stenosis in an adult.

PMID- 21967796
TI  - Left main coronary artery compression by a giant pulmonary artery aneurysm
      associated with large atrial septal defect and severe pulmonary hypertension.

PMID- 21967797
TI  - Diffuse coronary spasm mimicking acute thrombosis after stent implantation.

PMID- 21967799
TI  - Doctor-parent communication.

PMID- 21967798
TI  - Combination of channel-TURP and ILC versus standard TURP or ILC for elderly with
      benign prostatic hyperplasia: a randomized prospective trial.
AB  - PURPOSE: A prospective randomized controlled trial was performed in elderly
      patients with benign prostatic hyperplasia (BPH) to evaluate the clinical
      effectiveness of channel transurethral resection of the prostate (C-TURP)
      combined with an interstitial laser coagulation (ILC) technique during a 4-year
      follow-up period. METHODS: A total of 150 consecutive BPH patients were
      randomized to an ILC+C-TURP group (n = 50), an ILC group (n = 50) and a TURP
      group (n = 50). Urinary tract infection, acute urinary retention and retrograde
      ejaculation were monitored, and the retreatment rate, international prostate
      symptom score (IPSS) and maximum flow rate (Q(max)) were measured. RESULTS: A
      total of 142 patients completed the follow-up and were recruited for further
      analysis. At 1 month, the proportion of patients with urinary tract infection was
      similar between the C-TURP+ILC group and the TURP group (8.5 and 6.5%, p > 0.05),
      but significantly higher than that in the ILC group (51%, p < 0.001). Acute
      urinary retention was found in 30.6% of patients in the ILC group, but was not
      observed in the C-TURP+ILC and TURP groups. In the TURP group, the rate of
      retrograde ejaculation was significantly higher than that in the other 2 groups
      (p < 0.001). The retreatment rate was 8.5, 36.7 and 2.2% in the C-TURP+ILC, ILC
      and TURP groups, respectively (p < 0.001). When compared with baseline, the IPSS
      in the C-TURP+ILC, ILC and TURP groups was decreased by 70.6, 45.4, and 81.0%,
      respectively (ILC vs. C-TURP+ILC or TURP, p < 0.01) at the 48-month follow-up.
      One month after surgery, the Q(max) was significantly increased in the C-TURP+ILC
      group and the TURP group when compared with that at baseline (p < 0.01). The TURP
      group had the highest and the ILC group had the lowest increase in the Q(max) at
      the 12-, 24-, and 48-month follow-ups (p < 0.05). CONCLUSIONS: C-TURP+ILC is a
      safe and effective modality for the treatment of BPH, and exhibits favorable
      short-term clinical response and long-term durability. It is relatively
      reasonable and acceptable for treatment of high-risk elderly patients or those
      with a limited life expectancy.

PMID- 21967800
TI  - Effectiveness evaluation of an integrated automatic thermomechanic massage system
      (SMATH(r) system) in non-specific sub-acute and chronic low back pain - a
      randomized double-blinded controlled trial, comparing SMATH therapy versus sham
      therapy: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Low back pain (LBP) is a major health problem in modern society, with
      70-85% of the population experiencing LBP at some time in their lives. Each year,
      5-10% of the workforce misses work due to LBP, most for less than 7 days. Almost
      10% of all patients are at risk of developing chronic pain and disability. Little
      clinical evidence is available for the majority of treatments used in LBP
      therapy. However, moderate evidence exists for interdisciplinary rehabilitation,
      exercise, acupuncture, spinal manipulation, and cognitive behavioral therapy for
      subacute and chronic LBP. The SMATH(r) system (system for automatic
      thermomechanic massage in health) is a new medical device (MD) that combines
      basic principles of mechanical massage, thermotherapy, acupressure, infrared
      therapy, and moxibustion. SMATH(r) is suitable for automatic multidisciplinary
      treatment on patients with non-specific sub-acute and chronic LBP.
      METHODS/DESIGN: This paper describes the protocol for a double-blinded, sham
      controlled, randomized, single-center short term clinical trial in patients with
      non-specific sub-acute and chronic LBP aged 18 to 70 years. The primary outcome
      will be the effectiveness of SMATH(r) versus sham therapy (medical device without
      active principles) determined by evaluating self perceived physical function with
      Roland Morris Disability Questionnaire (RMDQ) scores after 4 weeks of treatment
      (end of treatment). Major secondary outcome will be effectiveness of SMATH(r)
      determined by evaluating self perceived physical function comparing RMDQ scores
      between end of treatment and baseline. The trial part of the study will take 7
      months while observational follow-up will take 11 months. The sample size will be
      72 participants (36 for each arm). The project has been approved by the Ethical
      Committee of Cremona Hospital, Italy on 29 November 2010. DISCUSSION: Compared to
      other medical specialties, physical and rehabilitation medicine (PRM) has not yet
      received the deserved recognition from clinicians and researchers in the
      scientific community, especially for medical devices. The best way to change this
      disadvantage is through well-conducted clinical research in sham-controlled
      randomized trials. Sham treatment groups are essential for improving the level of
      evidence-based practice in PRM. The present trial will counter the general lack
      of evidence concerning medical devices used in LBP therapy. TRIAL REGISTRATION:
      ISRCTN: ISRCTN08714168.

PMID- 21967801
TI  - Transglutaminase 2 facilitates the distant hematogenous metastasis of breast
      cancer by modulating interleukin-6 in cancer cells.
AB  - INTRODUCTION: Inflammation has been implicated in cancer aggressiveness. As
      transglutaminase 2 (TG2), which has been associated with inflammatory signaling,
      has been suggested to play a role in tumor behavior, we propose that TG2 may be
      an important linker inducing interleukin (IL)-6-mediated cancer-cell
      aggressiveness, including distant hematogenous metastasis. METHODS: To
      investigate the role for TG2 and IL-6, TG2-knocked-down and IL-6-knocked-down
      cancer cells were generated by using shRNA. Human breast cancer cell xenograft
      model in highly immunocompromised mice and human advanced breast cancer primary
      tumor tissue microarrays were used in this study. RESULTS: IL-6 production in
      human breast cancer cells was dependent on their TG2 expression level. In vitro
      tumor-sphere formation was dependent on TG2 and downstream IL-6 production from
      cancer cells. Primary tumor growth in the mammary fat pads and distant
      hematogenous metastasis into the lung was also dependent on TG2 and downstream IL
      6 expression levels. The effect of TG2 expression on human breast cancer distant
      metastasis was investigated by analyzing a tissue microarray of primary tumors
      from 412 patients with their clinical data after 7 years. TG2 expression in
      primary tumor tissue was inversely correlated with recurrence-free survival (P =
      0.019) and distant metastasis-free survival (DMFS) (P = 0.006) in patients with
      advanced breast cancer. Furthermore, by using public datasets that included a
      total of 684 breast cancer patients, we found that the combined high expression
      of TG2 and IL-6 was associated with shorter DMFS, compared with the high
      expression of IL-6 only (P = 0.013). CONCLUSIONS: We provide evidence that TG2 is
      an important link in IL-6-mediated tumor aggressiveness, and that TG2 could be an
      important mediator of distant metastasis, both in a xenograft animal model and in
      patients with advanced breast cancer.

PMID- 21967802
TI  - Damage associated molecular patterns within xenogeneic biologic scaffolds and
      their effects on host remodeling.
AB  - The immune response is an important determinant of the downstream remodeling of
      xenogeneic biologic scaffolds in vivo. Pro-inflammatory responses have been
      correlated with encapsulation and a foreign body reaction, while anti
      inflammatory reactions are associated with constructive remodeling. However, the
      bioactive and bioinductive molecules within the extracellular matrix (ECM) that
      induce this polarization are unclear, although it is likely that cellular
      remnants such as damage associated molecular patterns (DAMPs) retained within the
      scaffold may play a role. The present study investigated the immunomodulatory
      effects of common ECM scaffolds. Results showed that tissue source,
      decellularization method and chemical crosslinking modifications affect the
      presence of the well characterized DAMP - HMGB1. In addition, these factors were
      correlated with differences in cell proliferation, death, secretion of the
      chemokines CCL2 and CCL4, and up regulation of the pro-inflammatory signaling
      receptor toll-like receptor 4 (TLR4). Inhibition of HMGB1 with glycyrrhizin
      increased the pro-inflammatory response, increasing cell death and up regulating
      chemokine and TLR4 mRNA expression. The present study suggests the importance of
      HMGB1 and other DAMPS as bioinductive molecules within the ECM scaffold.
      Identification and evaluation of other ECM bioactive molecules will be an area of
      future interest for new biomaterial development.

PMID- 21967803
TI  - Granulysin Expression in Lymphocytes that Populate the Peripheral Blood and the
      Myocardium after an Acute Coronary Event.
AB  - We aimed to analyse granulysin (GNLY)-mediated cytotoxicity in the peripheral
      blood of patients with non-ST-segment elevation myocardial infarction (NSTEMI)
      treated with anti-ischaemic drug therapy. Thirty-nine NSTEMI patients with a
      median age of 70 years and 28 age-matched healthy subjects were enrolled in this
      study. On day 7 after MI, the number of GNLY(+) lymphocytes in the peripheral
      blood increased approximately six-fold of that in the healthy subjects, measured
      by flow cytometry. On day 14, the number of GNLY(+) cells significantly decreased
      in T, NKT, and both CD56(+dim) and CD56(+bright) NK subsets. GNLY(+) CD3(+) and
      GNLY(+) CD56(+) cells infiltrated central zone of myocardial infarction (MI). In
      persons who died in the first week after MI, GNLY(+) cells were found within
      accumulation of apoptotic leucocytes and reached the apoptotic cardiomyocytes in
      border MI zones probably due to the influence of interleukin-15 in peri-necrotic
      cardiomyocytes, as it is was shown by immunohistology. By day 28, the percentage
      of GNLY(+) lymphocytes in peripheral blood returned to the levels similar to that
      of the healthy subjects. Anti-GNLY mAb decreased apoptosis of K562 targets using
      peripheral blood NK cells from days 7 and 28 after MI, while in assays using
      cells from days 1 and 21, both anti-GNLY and anti-perforin mAbs were required to
      significantly decrease apoptosis. Using NK cells from day 14, K562 apoptosis was
      nearly absent. In conclusion, it seems that GNLY(+) lymphocytes, probably
      attracted by IL-15, not only participate partially in myocardial cell apoptosis,
      but also hasten resolution of cardiac leucocyte infiltration in patients with
      NSTEMI.

PMID- 21967804
TI  - Income-related health inequalities across regions in Korea.
AB  - INTRODUCTION: In addition to economic inequalities, there has been growing
      concern over socioeconomic inequalities in health across income levels and/or
      regions. This study measures income-related health inequalities within and
      between regions and assesses the possibility of convergence of socioeconomic
      inequalities in health as regional incomes converge. METHODS: We considered a
      total of 45,233 subjects (>= 19 years) drawn from the four waves of the Korean
      National Health and Nutrition Examination Survey (KNHANES). We considered true
      health as a latent variable following a lognormal distribution. We obtained ill
      health scores by matching self-rated health (SRH) to its distribution and used
      the Gini Coefficient (GC) and an income-related ill-health Concentration Index
      (CI) to examine inequalities in income and health, respectively. RESULTS: The GC
      estimates were 0.3763 and 0.0657 for overall and spatial inequalities,
      respectively. The overall CI was -0.1309, and the spatial CI was -0.0473. The
      spatial GC and CI estimates were smaller than their counterparts, indicating
      substantial inequalities in income (from 0.3199 in Daejeon to 0.4233 Chungnam)
      and income-related health inequalities (from -0.1596 in Jeju and -0.0844 in
      Ulsan) within regions.The results indicate a positive relationship between the GC
      and the average ill-health and a negative relationship between the CI and the
      average ill-health. Those regions with a low level of health tended to show an
      unequal distribution of income and health. In addition, there was a negative
      relationship between the GC and the CI, that is, the larger the income
      inequalities, the larger the health inequalities were. The GC was negatively
      related to the average regional income, indicating that an increase in a region's
      average income reduced income inequalities in the region. On the other hand, the
      CI showed a positive relationship, indicating that an increase in a region's
      average income reduced health inequalities in the region. CONCLUSION: The results
      suggest that reducing health inequalities across regions require a more equitable
      distribution of income and a higher level of average income and that the higher
      the region's average income, the smaller its health inequalities are.

PMID- 21967805
TI  - Cellular migration to electrospun poly(lactic acid) fibermats.
AB  - Nonwoven fabrics prepared via an electrospinning method, so-called electrospun
      fibermats, are expected to be promising scaffold materials for bone tissue
      engineering. In the present work, poly(L-lactic acid) (PLLA) fibermats,
      consisting of fibers with diameters ranging from 1 to 10 MUm, were prepared by
      electrospinning. Mouse osteoblast-like cells (MC3T3-E1) were seeded on the
      fibermats with various fiber diameters (10, 5 and 2 MUm; they are denoted by
      samples A, B and C, respectively) and cultured in two different directions in
      order to compare the migration behaviours into the scaffold of the normal
      condition and the anti-gravity condition. The cells in/on the fibermats were
      observed by laser confocal microscopy to estimate the cellular migration ability
      into them. When the MC3T3-E1 cells were cultured in the normal direction, the
      thickness of their layer increased to approx. 90 MUm in the sample A, consisting
      of 10-MUm fibers after 13 days of culture, while that in the sample C, consisting
      of 2-MUm fibers, did not increase. When the MC3T3-E1 cells were cultured in the
      anti-gravity condition, the thickness of the cell layer in the sample A increased
      to approx. 60 MUm. These results mean that the MC3T3-E1 cells migrated into the
      inside of sample A in either the normal direction or the anti-gravity one. The
      cellular proliferation showed no significant difference among the fibermats with
      three different fiber diameters; MC3T3-E1 cells on the fibermat with 2 MUm fiber
      diameter grew two-dimensionally, while they grew three-dimensionally in the
      fibermat with 10 MUm fiber diameter. 

PMID- 21967806
TI  - Multi-target drug discovery in anti-cancer therapy: fragment-based approach
      toward the design of potent and versatile anti-prostate cancer agents.
AB  - Prostate cancer (PCa) is the second-leading cause of cancer deaths among men in
      the around the world. Understanding the biology of PCa is essential to the
      development of novel therapeutic strategies, in order to prevent this disease.
      However, after PCa make metastases, chemotherapy plays an extremely important
      role. With the pass of the time, PCa cell lines become resistant to the current
      anti-PCa drugs. For this reason, there is a necessity to develop new anti-PCa
      agents with the ability to be active against several PCa cell lines. The present
      work is an effort to overcome this problem. We introduce here the first multi
      target approach for the design and prediction of anti-PCa agents against several
      cell lines. Here, a fragment-based QSAR model was developed. The model had a
      sensitivity of 88.36% and specificity 89.81% in training series. Also, the model
      showed 94.06% and 92.92% for sensitivity and specificity, respectively. Some
      fragments were extracted from the molecules and their contributions to anti-PCa
      activity were calculated. Several fragments were identified as potential
      substructural features responsible of anti-PCa activity and new molecular
      entities designed from fragments with positive contributions were suggested as
      possible anti-PCa agents.

PMID- 21967807
TI  - Identification of a potent and selective sigma1 receptor agonist potentiating NGF
      induced neurite outgrowth in PC12 cells.
AB  - Herein we report the synthesis, drug-likeness evaluation, and in vitro studies of
      new sigma (sigma) ligands based on arylalkenylaminic scaffold. For the most
      active olefin the corresponding arylalkylamine was studied. Novel
      arylalkenylamines generally possess high sigma(1) receptor affinity (K(i) values
      <25 nM) and good sigma(1)/sigma(2) selectivity (K(i)sigma(2) >100). Particularly,
      the piperidine derivative (E)-17 and its arylalkylamine analog (R,S)-33 were
      observed to be excellent sigma(1) receptor ligands (K(i)=0.70 and 0.86 nM,
      respectively) and to display significantly high selectivity over sigma(2), MU-,
      and kappa-opioid receptors and phencyclidine (PCP) binding site of the N-methyl-d
      aspartate (NMDA) receptors. Moreover in PC12 cells (R,S)-33 promoted the nerve
      growth factor (NGF)-induced neurite outgrowth and elongation. Co-administration
      of the selective sigma(1) receptor antagonist BD-1063 totally counteracted this
      effect, confirming that sigma(1) receptors are involved in the (R,S)-33
      modulation of the NGF effect in PC12 cells and suggesting a sigma(1) agonist
      profile. As a part of our work, a threedimensional sigma(1) pharmacophore model
      was also developed employing GALAHAD methodology. Only active compounds were used
      for deriving this model. The model included two hydrophobes and a positive
      nitrogen as relevant features and it was able to discriminate between molecules
      with and without affinity toward sigma(1) receptor subtype.

PMID- 21967808
TI  - Improvement in oral bioavailability of 2,4-diaminopyrimidine c-Met inhibitors by
      incorporation of a 3-amidobenzazepin-2-one group.
AB  - The hepatocyte growth factor (HGF)-c-Met signaling axis is involved in the
      mediation of many biological activities, including angiogenesis, proliferation,
      cell survival, cell motility, and morphogenesis. Dysregulation of c-Met signaling
      (e.g., overexpression or increased activation) is associated with the
      proliferation and metastasis of a wide range of tumor types, including breast,
      liver, lung, colorectal, gastric, bladder, and prostate, among others. Inhibiting
      the HGF-c-Met pathway is predicted to lead to anti-tumor effects in many cancers.
      Elaboration of the SAR around a series of 2,4-diaminopyrimidines led to a number
      of c-Met inhibitors in which pharmaceutical properties were modulated by
      substituents appended on the C2-benzazepinone ring. In particular, certain-3
      amidobenzazepin-2-one analogs had improved oral bioavailability and were
      evaluated in PK/PD and efficacy models. Lead compounds demonstrated tumor stasis
      with partial regressions when evaluated in a GTL-16 tumor xenograft mouse model.

PMID- 21967809
TI  - Positive spill-over effects of ART scale up on wider health systems development:
      evidence from Ethiopia and Malawi.
AB  - BACKGROUND: Global health initiatives have enabled the scale up of antiretroviral
      treatment (ART) over recent years. The impact of HIV-specific funds and
      programmes on non-HIV-related health services and health systems in genera has
      been debated extensively. Drawing on evidence from Malawi and Ethiopia, this
      article analyses the effects of ART scale-up interventions on human resources
      policies, service delivery and general health outcomes, and explores how
      synergies can be maximized. METHODS: Data from Malawi and Ethiopia were compiled
      between 2004 and 2009 and between 2005 and 2009, respectively. We developed a
      conceptual health systems framework for the analysis. We used the major changes
      in human resources policies as an entry point to explore the wider health systems
      changes. RESULTS: In both countries, the need for an HIV response triggered an
      overhaul of human resources policies. As a result, the health workforce at health
      facility and community level was reinforced. The impact of this human resources
      trend was felt beyond the scale up of ART services; it also contributed to an
      overall increase in functional health facilities providing curative, mother and
      child health, and ART services. In addition to a significant increase in ART
      coverage, we observed a remarkable rise in user rates of non-HIV health services
      and an improvement in overall health outcomes. CONCLUSIONS: Interventions aimed
      at the expansion of ART services and improvement of long-term retention of
      patients in ART care can have positive spill-over effects on the health system.
      The responses of Malawi and Ethiopia to their human resources crises was
      exceptional in many respects, and some of the lessons learnt can be useful in
      other contexts. The case studies show the feasibility of obtaining improved
      health outcomes beyond HIV through scaled-up ART interventions when these are
      part of a long-term, system-wide health plan supported by all decision makers and
      funders.

PMID- 21967810
TI  - Antiallodynic effect and side effects of Phalpha1beta, a neurotoxin from the
      spider Phoneutria nigriventer: comparison with omega-conotoxin MVIIA and
      morphine.
AB  - Phalpha1beta is a potent toxin obtained from the spider Phoneutria nigriventer
      that blocks neuronal voltage-sensitive Ca(2+) channels. This study compared the
      antiallodynic effects of Phalpha1beta, omega-conotoxin MVIIA and morphine in mice
      and their side effects in rats. Mechanical allodynia was measured in mice
      receiving single intrathecal administration of Phalpha1beta, omega-conotoxin
      MVIIA or morphine before or after the incisional plantar procedure. The effect of
      the treatments on cardiovascular profile and global neurological were evaluated
      in rats. The expression of pro or anti-inflammatory cytokines of human polymorph
      mononuclear cells was also evaluated. Preemptive use of omega-conotoxin MVIIA
      (1.0 or 10 pmol/site) or morphine (1000 pmol/site) induced shorter antiallodynic
      effect than Phalpha1beta (100 pmol/site) in mice. Post-incision administration of
      Phalpha1beta (200 pmol/site) induced longer mechanical antiallodynic effect than
      omega-conotoxin MVIIA (1.0 or 10 pmol/site) or morphine (1000 pmol/site).
      Intrathecal injection of Phalpha1beta (200 pmol/site) and morphine (433
      pmol/site) did not change while omega-conotoxin MVIIA (100 pmol/site) increased
      the heart rate in rats 3 h after its administration. Phalpha1beta (200
      pmol/site), omega-conotoxin MVIIA (100 pmol/site) and morphine (433 pmol/site)
      did not change mean arterial pressure 0.5 and 3 h after their administration. The
      treatments did not alter neurological performance assessed by global neurological
      evaluation and open-field test. The tested drugs did not induced expression of
      pro or anti-inflammatory cytokines in CD4 monocytes. In conclusion, preemptive
      administration Phalpha1beta in mice induced longer antiallodynic effect than
      omega-conotoxin MVIIA and morphine. Phalpha1beta also induced a longer mechanical
      antiallodynic effect than omega-conotoxin MVIIA and morphine when used after the
      surgical incision. The present results suggest that Phalpha1beta has a potential
      application in the management of postoperative pain with low side effects.

PMID- 21967811
TI  - Heminecrolysin, a potential immunogen for monospecific antivenom production
      against Hemiscorpius lepturus scorpion.
AB  - Serotherapy against Hemiscorpius (H.) lepturus scorpion sting is based on the
      administration of equine polyvalent antivenom prepared against a mixture of six
      venoms. In a previous study, we reported the identification of Heminecrolysin, a
      33 kDa H. lepturus venom protein endowed with a sphingomyelinase D, hemolytic and
      dermonecrotic activities. We aimed herein to investigate the capacity of
      Heminecrolysin to generate antibodies able to neutralize the major
      physiopathological properties of H. lepturus envenomation, e.g. hemolysis and
      dermonecrosis. The efficiency of anti-Heminecrolysin antibodies was compared to
      that of anti-whole venom. Our results demonstrated that Heminecrolysin elicits
      high levels of specific IgGs. Anti-Heminecrolysin, similarly to anti-whole venom
      antibodies, totally inhibited H. lepturus hemolytic effect when up to 5 times the
      half maximal effective concentration of venom were used. Phosphatidylserine
      exposure on the external lipid monolayer of human red blood cells treated with
      whole venom was also fully blocked by both anti-sera. Experimental envenomation
      of rabbits showed that anti-Heminecrolysin antibodies were as potent as anti-H.
      lepturus antibodies to neutralize dermonecrotic effects when up to 4 times the
      minimal necrotic dose of venom were injected. However, inflammatory reaction was
      better controlled with anti-whole venom sera. In conclusion, Heminecrolysin
      elicits protective antibodies of comparable potency to those elicited by
      immunization with whole venom.

PMID- 21967812
TI  - Clinical effects and treatment of envenoming by Hoplocephalus spp. snakes in
      Australia: Australian Snakebite Project (ASP-12).
AB  - There is limited information on envenoming by snakes of the genus Hoplocephalus
      from Eastern Australia. We investigated the clinical and laboratory features of
      patients with definite Hoplocephalus spp. bites including antivenom treatment,
      recruited to the Australian Snakebite Project. There were 15 definite
      Hoplocephalus spp. bites based on expert identification including eight by
      Hoplocephalus stephensi (Stephen's banded snakes), four by Hoplocephalus
      bungaroides (broad-headed snake) and three by H. bitorquatus (pale-headed snake).
      Envenoming occurred in 13 patients and was similar for the three species with
      venom induced consumption coagulopathy (VICC) in all envenomings. Seven patients
      had an INR >12 and partial VICC, with only incomplete fibrinogen consumption,
      occurred in three patients. Systemic symptoms occurred in eight patients.
      Myotoxicity and neurotoxicity did not occur. H. stephensi venom was detected in
      all three H. stephensi envenomings (1.1, 44 and 81 ng/mL) for whom pre-antivenom
      blood samples were available, and not detected in one without envenoming. In two
      cases with post-antivenom blood samples, venom was not detected after tiger snake
      antivenom (TSAV) was given. In vitro binding studies demonstrated that TSAV
      concentrations of 50mU/mL are sufficient to bind the majority of free H.
      stephensi venom components at concentrations above those detected in envenomed
      patients (100 ng/mL). Eleven patients received antivenom, median dose 2 vials
      (Range: 1 to 5 vials), which was TSAV in all but one case, where polyvalent
      antivenom was used. Immediate hypersensitivity reactions occurred in six cases
      including one case of anaphylaxis. Envenoming by Hoplocephalus spp. causes VICC
      and systemic symptoms, making it clinically similar to brown snake (Pseudonaja
      spp.) envenoming. Based on in vitro studies reported here, patients may be
      treated with one vial of TSAV, although one vial of brown snake antivenom may
      also be sufficient.

PMID- 21967813
TI  - Coagulopthy, acute kidney injury and death following Hypnale zara envenoming: the
      first case report from Sri Lanka.
AB  - Snakebite is a major medical problem in developing Asia. Hump-nosed pit viper
      (Genus Hypnale) causes the most number of snakebites with significant morbidity
      and mortality in Sri Lanka. Even though there are three species (Hypnale hypnale,
      Hypnale zara and Hypnale nepa) in Sri Lanka there are few published literature on
      species-specific clinico-epidemiological data. This report describes an
      authenticated fatal case of a 47 years old male due to coagulopthy and acute
      kidney injury following envenoming by H. zara in Sri Lanka.

PMID- 21967814
TI  - Diesel exhaust particulates exacerbate asthma-like inflammation by increasing CXC
      chemokines.
AB  - Particulate matter heavily pollutes the urban atmosphere, and several studies
      show a link between increased ambient particulate air pollution and exacerbation
      of pre-existing pulmonary diseases, including asthma. We investigated how diesel
      exhaust particulates (DEPs) aggravate asthma-like pulmonary inflammation in a
      mouse model of asthma induced by a house dust extract (HDE) containing cockroach
      allergens and endotoxin. BALB/c mice were exposed to three pulmonary challenges
      via hypopharyngeal administration of an HDE collected from the home of an
      asthmatic child. One hour before each pulmonary challenge, mice were exposed to
      DEP or PBS. Pulmonary inflammation was assessed by histological features,
      oxidative stress, respiratory physiological features, inflammatory cell
      recruitment, and local CXC chemokine production. To prove the role of CXC
      chemokines in the augmented inflammation, CXC chemokine-specific antibodies were
      delivered to the lungs before DEP exposure. DEP exacerbated HDE-induced airway
      inflammation, with increased airway mucus production, oxidative stress,
      inflammatory cell infiltration, bronchoalveolar lavage concentrations of CXC
      chemokines, and airway hyperreactivity. Neutralization of airway keratinocyte
      derived chemokine and macrophage inflammatory protein-2 significantly improves
      the respiratory function in addition to decreasing the infiltration of
      neutrophils and eosinophils. Blocking the chemokines also decreased airway mucus
      production. These results demonstrate that DEP exacerbates airway inflammation
      induced by allergen through increased pulmonary expression of the CXC chemokines
      (keratinocyte-derived chemokine and macrophage inflammatory protein-2).

PMID- 21967815
TI  - Increased expression of 14-3-3beta promotes tumor progression and predicts
      extrahepatic metastasis and worse survival in hepatocellular carcinoma.
AB  - 14-3-3beta is implicated in cell survival, proliferation, migration, and tumor
      growth; however, its clinical relevance in tumor progression and metastasis have
      never been elucidated. To evaluate the clinical significance of 14-3-3beta, we
      analyzed the association of 14-3-3beta expression and clinicopathologic
      characteristics in primary and subsequent metastatic tumors of hepatocellular
      carcinoma patients. 14-3-3beta was expressed abundantly in 40 of 55 (70.7%)
      primary tumors. Increased 14-3-3beta expression in primary tumors predicted a
      higher 5-year cumulative incidence of subsequent extrahepatic metastasis, and
      multivariate analysis revealed 14-3-3beta overexpression was an independent risk
      factor for extrahepatic metastasis. Patients with increased 14-3-3beta expression
      in primary tumors had worse 5-year overall survival rates, and 14-3-3beta
      overexpression was an independent prognostic factor on Cox regression analysis.
      Furthermore, stably overexpressed 14-3-3beta enhanced hepatocellular carcinoma
      cell migration and proliferation and increased anchorage-independent cell growth.
      In addition, in vivo study in a nude-mice model showed tumor formation
      significantly increased with 14-3-3beta overexpression. In conclusion, this is
      the first report to show that increased 14-3-3beta expression is associated with
      subsequent extrahepatic metastasis and worse survival rates, as well as cancer
      progression of hepatocellular carcinoma. Thus, 14-3-3beta may be a novel
      prognostic biomarker and therapeutic target in hepatocellular carcinoma.

PMID- 21967816
TI  - Insulin resistance and metabolic hepatocarcinogenesis with parent-of-origin
      effects in A*B mice.
AB  - Insulin resistance is a defining feature of metabolic syndrome and type 2
      diabetes mellitus but also may occur independently of these conditions.
      Nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of these
      disorders, increases the risk of hepatocellular carcinoma (HCC). However,
      mechanisms linking hyperinsulinemia to NAFLD and HCC require clarification. We
      describe a novel model of primary insulin resistance and HCC with strong parent
      of-origin effects. Male AB6F1 (A/JCr dam * C57BL/6 sire) but not B6AF1 (B6 dam *
      A/J sire) mice developed spontaneous insulin resistance, NAFLD, and HCC without
      obesity or diabetes. A survey of mitochondrial, imprinted, and sex-linked traits
      revealed modest associations with X-linked genes. However, a diet-induced obesity
      study, including B6.A chromosome substitution-strain (consomic) mice, showed no
      segregation by sex chromosome. Thus, parent-of-origin effects were specified
      within the autosomal genome. Next, we interrogated mechanisms of insulin
      associated hepatocarcinogenesis. Steatotic hepatocytes exhibited adipogenic
      transition characterized by vacuolar metaplasia and up-regulation of vimentin,
      adipsin, fatty acid translocase (CD36), peroxisome proliferator-activated
      receptor-gamma, and related products. This profile was largely recapitulated in
      insulin-supplemented primary mouse hepatocyte cultures. Importantly, pyruvate
      kinase M2, a fetal anabolic enzyme implicated in the Warburg effect, was
      activated by insulin in vivo and in vitro. Thus, our study reveals parent-of
      origin effects in heritable insulin resistance, implicating adipogenic transition
      with acquired anabolic metabolism in the progression from NAFLD to HCC.

PMID- 21967818
TI  - The value of pulmonary contusion volume measurement with three-dimensional
      computed tomography in predicting acute respiratory distress syndrome
      development.
AB  - BACKGROUND: This study reports the value of accurate pulmonary contusion (PC)
      volume measurement with 3-dimensional computed tomography (CT) in predicting
      acute respiratory distress syndrome (ARDS) development. METHODS: The study
      enrolled all patients who were diagnosed with PC on admission by CT and had a
      chest Abbreviated Injury Score (AIS) exceeding 2 between January 1, 2010, and
      October 31, 2010. PC volume was measured from 3-dimensional reconstructions of
      admission chest CTs and expressed as a percentage of total lung volume. Admission
      data were prospectively collected. The independent predictor of ARDS development
      was established. The accuracy and value of the predictors were analyzed, and the
      influence of PC volume percentage on clinical outcomes was demonstrated. RESULTS:
      The average PC volume percentage was 21.86% +/- 13.90% (range, 5.6% to 61.0%),
      which was inconsistently correlated with the admission partial pressure of
      oxygen/fraction of inspired oxygen ratio (R(2) = 0.083). ARDS was diagnosed in 26
      patients (43.3%) and pneumonia in 21 (35.0%). The admission partial pressure of
      oxygen/fraction of inspired oxygen ratio (p = 0.003) and PC volume percentage (p
      = 0.01) were independent predictive factors of ARDS development. Patients with a
      PC volume percentage exceeding the best cutoff of 21.5% were defined as the
      severe PC group. The partial pressure of oxygen/fraction of inspired oxygen
      ratio, the needed maximal positive end-expiratory pressure level, and ARDS
      incidence between the severe group and the general group was significantly
      different (p <.05). CONCLUSIONS: Pulmonary contusion volume measured using 3
      dimensional CT is feasible in emergency departments and helpful to identify
      patients at high-risk for ARDS.

PMID- 21967817
TI  - Neuroglobin is an endogenous neuroprotectant for retinal ganglion cells against
      glaucomatous damage.
AB  - Neuroglobin (NGB), a newly discovered member of the globin superfamily, may
      regulate neuronal survival under hypoxia or oxidative stress. Although NGB is
      greatly expressed in retinal neurons, the biological functions of NGB in retinal
      diseases remain largely unknown. We investigated the role of NGB in an
      experimental model of glaucoma, a neurodegenerative disorder that usually
      involves elevation of intraocular pressure (IOP). Elevated IOP is thought to
      induce oxidative stress in retinal ganglion cells (RGCs), thereby causing RGC
      death and, eventually, blindness. We found that NGB plays a critical role in
      increasing RGC resistance to ocular hypertension and glaucomatous damage.
      Elevation of IOP stimulated a transient up-regulation of endogenous NGB in RGCs.
      Constitutive overexpression of NGB in transgenic mice prevented RGC damage
      induced by glutamate cytotoxicity in vitro and/or by chronic IOP elevation in
      vivo. Moreover, overexpression of NGB attenuated ocular hypertension-induced
      superoxide production and the associated decrease in ATP levels in mice,
      suggesting that NGB acts as an endogenous neuroprotectant to reduce oxidative
      stress and improve mitochondrial function, thereby promoting RGC survival. Thus,
      NGB may modulate RGC susceptibility to glaucomatous neural damage. Manipulating
      the expression and bioactivity of NGB may represent a novel therapeutic strategy
      for glaucoma.

PMID- 21967819
TI  - Bypass versus drug-eluting stents at three years in SYNTAX patients with diabetes
      mellitus or metabolic syndrome.
AB  - BACKGROUND: Diabetes mellitus increases adverse outcomes after coronary
      revascularization; however, the impact of metabolic syndrome is unclear. We
      examined the impact of diabetes and metabolic syndrome on coronary artery bypass
      graft surgery (CABG) and stenting outcomes to determine the optimal
      revascularization option for the treatment of complex coronary artery disease.
      METHODS: Patients (n = 1,800) with left main or three-vessel disease or both were
      randomly allocated to treatment with a TAXUS Express(2) paclitaxel-eluting stent
      (PES) or CABG, and were included in predefined nondiabetic (n = 1,348) or
      diabetic subgroups (n = 452); 258 patients with diabetes also had metabolic
      syndrome. RESULTS: Among diabetic patients, the 3-year major adverse cardiac and
      cerebrovascular event (MACCE) rate (22.9% CABG, 37.0% PES; p = 0.002) and
      revascularization rate (12.9% CABG, 28.0% PES; p < 0.001) were higher after PES
      treatment. Diabetes increased MACCE rates among PES-treated patients, but had
      little impact on results after CABG. Compared with CABG, PES treatment yielded
      comparable MACCE in diabetic patients (30.5% versus 29.8%, p =0.98) and
      nondiabetic patients (20.2% versus 20.3%, p =0.99) with low Synergy Between
      Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) study
      scores of 22 or less. For patients with SYNTAX Scores of 33 or greater, MACCE
      rates were lower with CABG (18.5% versus 45.9%, p < 0.001 diabetic; 19.8% versus
      30.0%, p = 0.01 nondiabetic). Metabolic syndrome did not significantly predict
      MACCE or repeat revascularization. CONCLUSIONS: These exploratory analyses
      suggest that among diabetic patients with complex left main or three-vessel
      disease, or both, 3-year MACCE is higher after PES compared with CABG. Although
      PES is a potential treatment option in patients with less complex lesions, CABG
      should be the revascularization option of choice for patients with more complex
      anatomic disease, especially with concurrent diabetes. Metabolic syndrome had
      little impact on 3-year outcomes.

PMID- 21967820
TI  - Addition of IGF-I to storage-cooled boar semen and its effect on sperm quality.
AB  - OBJECTIVE: To evaluate in vitro IGF-I treatment during warming of storage-cooled
      boar semen and its effect on seminal quality parameters and metabolism in
      spermatic cells. DESIGN: Semen samples (n=7) warmed after stored at 15 degrees C
      for 24 or 72h were divided into four equal parts. Different IGF-I concentrations
      (0, 50, 100 and 150ng/mL) were added to the semen samples. The samples were
      incubated at 37 degrees C, and assessments were made after 0 and 120min of
      incubation. RESULTS: For semen samples that were stored for 24h, the addition of
      IGF-I had no effect (p>0.05) on the total motility and intensity of movements by
      spermatic cells, osmotic resistance, live:dead cell ratio or total spermatic
      abnormalities. However, incubation with 150ng/mL IGF-I did decrease glutathione
      peroxidase activity (p<0.05) and reduce lipid peroxidation after 120min of
      incubation. For semen samples stored for 72h and incubated with IGF-I for 120min,
      there was a linear relationship between the IGF-I concentration and the live:dead
      ratio (p<0.05). There was a quadratic relationship between the IGF-I
      concentration and both the osmotic resistance (peak results at IGF-I=62.4ng/mL)
      and glutathione peroxidase activity (peak results at IGF-I=77.8ng/mL). There was
      no effect on lipid peroxidation (p>0.05) after 120min of incubation. Addition of
      IGF-I also decreased fructose utilization by spermatic cells regardless of semen
      storage time (p<0.05). CONCLUSION: This study suggests that IGF-I may be
      beneficial to semen stored for longer periods of time. Adding 150ng/mL IGF-I
      improved the quality of semen stored for 24h, and adding 78ng/mL IGF-I improved
      the quality of semen stored for 72h.

PMID- 21967821
TI  - Which experiences of health care delivery matter to service users and why? A
      critical interpretive synthesis and conceptual map.
AB  - OBJECTIVE: Patients' experiences are often treated as health care quality
      indicators. Our aim was to identify the range of experiences of health care
      delivery that matter to patients and to produce a conceptual map to facilitate
      consideration of why they matter. METHODS: Broad-based review and critical
      interpretive synthesis of research literature on patients' perspectives of health
      care delivery. We recorded experiences reported by a diverse range of patients on
      'concept cards', considered why they were important, and explored various ways of
      organizing them, including internationally recognized health care quality
      frameworks. We developed a conceptual map that we refined with feedback from
      stakeholders. RESULTS: Patients identify many health care experiences as
      important. Existing health care quality frameworks do not cover them all. Our
      conceptual map presents a rich array of experiences, including health care
      relationships (beyond communication) and their implications for people's valued
      capabilities (e.g. to feel respected, contribute to their care, experience
      reciprocity). It is organized to reflect our synthesis argument, which links
      health care delivery to what people are enabled (or not) to feel, be and do. The
      map highlights the broad implications of the social dynamics of health care
      delivery. Experiences are labelled from a patient's perspective, rendering the
      importance of responsiveness to individuals axiomatic. CONCLUSIONS: Our
      conceptual map identifies and helps explain the importance of diverse experiences
      of health care delivery. It challenges and helps policy-makers, service providers
      and researchers to attend to the range of experiences that matter, and to take
      seriously the need for responsiveness to individuals.

PMID- 21967822
TI  - Competition in the NHS: a provider perspective.
AB  - OBJECTIVE: To analyse how competition is experienced and characterized by NHS and
      independent sector acute care providers in the English National Health Service
      (NHS). METHODS: Semi-structured interviews with 49 senior staff in 15 NHS trusts
      and independent sector providers between November 2008 and April 2009, in
      England. RESULTS: The market was predominantly defined based on geographical
      proximity. Competition was mainly on the periphery of catchment areas but markets
      were differentiated based on the scope and type of services. Niche providers,
      specialist hospitals and tertiary centres did not directly compete with district
      general hospital-type providers. Competitors were increasingly primary and
      community care providers, while there was little perceived threat from the
      private sector. There were many examples of how different providers (both NHS and
      independent sector) were co-operating and collaborating. Patients and general
      practitioners (GPs) appeared to be loyal to local providers. CONCLUSION: The
      providers' view of the market and the relevance of historical relationships and
      loyalties suggest fine grained variations in competition which is consistent with
      a relational rather than structural approach to competition. Also the evidence on
      embeddedness of relationships implies that collaboration might be a strong lever
      for quality improvement locally. Finally, some of the agreements found might be
      deemed in breach of the rules of competition but they may well be in the
      interests of patients and taxpayers, with implications for regulation in publicly
      funded health care systems.

PMID- 21967823
TI  - Climate for evidence-informed health systems: a profile of systematic review
      production in 41 low- and middle-income countries, 1996-2008.
AB  - OBJECTIVE: To describe systematic review production in 41 countries in Africa,
      the Americas, Asia and the eastern Mediterranean to understand one dimension of
      the climate for evidence-informed health systems and to provide a baseline for an
      evaluation of knowledge translation initiatives. METHODS: Our focus was
      systematic reviews published between 1996 and 2008 that had a corresponding
      author based in, or that appeared to target, one of the countries in these
      regions. We searched both Medline and Embase using validated search strategies,
      identified citations with a country name in the corresponding author's
      institutional affiliation or as a textword (i.e., an explicit mention in the
      title or abstract) or keyword, and coded articles describing a systematic review.
      We followed the same citation identification procedure for Health Systems
      Evidence, a database containing systematic reviews about health systems. RESULTS:
      Systematic review production increased between three-fold (for Africa in Medline)
      and 110-fold (for Asia in Embase) between the first period (1996-2002) and second
      period (2003-2008). In the second period, China was more often the home of
      corresponding authors and the target of reviews than any other country. No
      systematic reviews were produced by a corresponding author based in nine
      countries, or appeared to target five countries. Only 48 reviews identified
      through Medline and Embase addressed health systems, and 35 health systems
      reviews identified through Health Systems Evidence addressed these countries.
      CONCLUSION: In many countries, those seeking to support evidence-informed health
      systems cannot turn to experienced local systematic reviewers to help them to
      find and use systematic reviews or to conduct reviews on high priority topics
      when none exists. These findings suggest the need for local capacity-building
      initiatives.

PMID- 21967824
TI  - Failure Mode and Effects Analysis: views of hospital staff in the UK.
AB  - OBJECTIVE: To explore health care professionals' experiences and perceptions of
      Failure Mode and Effects Analysis (FMEA), a team-based, prospective risk analysis
      technique. METHODS: Semi-structured interviews were conducted with 21 operational
      leads (20 pharmacists, one nurse) in medicines management teams of hospitals
      participating in a national quality improvement programme. Interviews were
      transcribed, coded and emergent themes identified using framework analysis.
      RESULTS: Themes identified included perceptions and experiences of participants
      with FMEA, validity and reliability issues, and FMEA's use in practice. FMEA was
      considered to be a structured but subjective process that helps health care
      professionals get together to identify high risk areas of care. Both positive and
      negative opinions were expressed, with the majority of interviewees expressing
      positive views towards FMEA in relation to its structured nature and the use of a
      multidisciplinary team. Other participants criticised FMEA for being subjective
      and lacking validity. Most likely to restrict its widespread use were its time
      consuming nature and its perceived lack of validity and reliability. CONCLUSION:
      FMEA is a subjective but systematic tool that helps identify high risk areas, but
      its time consuming nature, difficulty with the scores and perceived lack of
      validity and reliability may limit its widespread use.

PMID- 21967825
TI  - 'Animateurs' and animation: what makes a good commissioning manager?
AB  - OBJECTIVES: To examine the managerial behaviours adopted by commissioning
      managers in English primary care trusts (PCTs), and to explore the impact of
      these behaviours. METHODS: Qualitative case studies were undertaken in four PCTs,
      focusing on staff engaged in the commissioning of hospital services. Both formal
      and informal observation were undertaken (150 hours), and 41 in-depth interviews
      conducted with managers and general practitioners (GPs). RESULTS: Managers
      adopted many managerial behaviours familiar from the literature, including
      sharing information, and networking inside and outside the organization. Multiple
      organizational layers and unclear decision-making processes hindered this
      activity. In addition, some managers with responsibility for facilitating
      practice-based commissioning (PbC) adopted a managerial mode that we have called
      being an 'animateur'. This approach involved the active management of disparate
      groups of people over whom the manager had no authority, and appeared to be a
      factor in determining success. It was facilitated by managerial autonomy and was
      more prevalent where managers were seen to have legitimacy. Some organizational
      practices appeared to inhibit its development. CONCLUSIONS: From 2012/13 it is
      planned that GPs will be taking more responsibility for commissioning in the
      English NHS. This research suggests that managers of the new commissioning
      organizations will require a deep and contextualized understanding of the NHS and
      that it is important that organizational processes do not inhibit managerial
      behaviour. Legitimacy may be an issue in contexts were managers are automatically
      transferred from their existing appointments.

PMID- 21967826
TI  - Melting bones: The social construction of postmenopausal osteoporosis in Turkey.
AB  - The increased medicalization of different life stages, including menopause, is a
      subject studied mostly in the Western context. Examining medicalization in the
      non-Western world advances discussions of body, identity and health. In this
      paper, I analyze the discourses around postmenopausal osteoporosis in Turkey,
      focusing on the different constructions of risk in the medical and popular
      literature. The empirical basis of the paper draws on ethnographic research done
      in Istanbul, Turkey between June 2006 and March 2007. The research includes
      participant observation in gynecology clinics, interviews with clinicians and
      menopausal women and archival research on the representations of menopause in the
      Turkish media between 1999 and 2006. Referred to as kemik erimesi (melting of the
      bones) in colloquial Turkish, osteoporosis has been an essential component in the
      medicalization of menopause in Turkey. I argue that postmenopausal osteoporosis
      is defined as a combination of embodied risk, which is related to the definition
      of menopause as a risky period, and lifestyle risk, demonstrated in discussions
      around "traditional" vs. "modern" clothing and healthcare habits. The Turkish
      example emphasizes the importance of local conditions in defining medical risk
      and complicates the embodied vs. lifestyle risk categories.

PMID- 21967827
TI  - Self assembly of human septin 2 into amyloid filaments.
AB  - Septins are a conserved group of GTP-binding proteins that form hetero-oligomeric
      complexes which assemble into filaments. These are essential for septin function,
      including their role in cytokinesis, cell division, exocytosis and membrane
      trafficking. Septin 2 (SEPT2) is a member of the septin family and has been
      associated with neurofibrillary tangles and other pathological features of senile
      plaques in Alzheimer's disease. An in silico analysis of the amino acid sequence
      of SEPT2 identified regions with a significant tendency to aggregate and/or form
      amyloid. These were all observed within the GTP-binding domain. This was
      consistent with the experimental identification of a structure rich in beta-sheet
      during temperature induced unfolding transitions observed for both the full
      length protein and the GTP-binding domain alone. This intermediate state is
      characterized by irreversible aggregation and has the ability to bind Thioflavin
      T, suggesting its amyloid nature. Under electron microscopy, fibers extending for
      several micrometers in length could be visualized. The results shown in this
      study support the hypothesis that single septins, when present in excess or with
      unbalanced stoichiometries, may be unstable and assemble into amyloid-like
      structures.

PMID- 21967828
TI  - An optimized method to assess in vivo efficacy of antithrombotic drugs using
      optical coherence tomography and a modified Doppler flow system.
AB  - INTRODUCTION: Animal models of venous and arterial thrombosis are extremely
      useful to study the efficacy of antithrombotic agents. Variability in efficacy
      data is often observed in those preclinical studies. The goal of this study was
      to optimize the methodology for assessing antithrombotic drug efficacy by the use
      of optical coherence tomography (OCT) and a modified Doppler flow system in rat
      models of thrombosis. METHODS: Thrombus formation was assessed in both the rat
      venous and arterial ferric chloride (FeCl(3)) models of thrombosis. In the venous
      model, thrombus volume post-treatment was measured using OCT, and data were
      correlated against the thrombus weight. In the arterial model, the time to
      occlusion was measured using a Doppler flow probe connected to a perivascular
      flow module which allowed the reporting of dynamic blood flow data every 30s.
      Heparin (130 or 165U/kg), argatroban (4.5mg/kg), bivalirudin (1.3mg/kg) or saline
      were administered intravenously. RESULTS: In the venous model, for all treatment
      groups a strong linear correlation (R(2)=0.998) was observed between thrombus
      volume measured by OCT and thrombus weight. In the arterial model, using a high
      sampling rate of a dynamic blood flow using a modified Doppler flow system
      provided data accuracy and precision of the time to occlusion measurement.
      DISCUSSION: This study demonstrates that OCT is a powerful tool for the
      assessment of antithrombotic drug efficacy. Furthermore, it shows that a high
      Doppler sampling rates of dynamic blood flow leads to data accuracy and
      precision.

PMID- 21967829
TI  - Bandgap engineering of zigzag graphene nanoribbons by manipulating edge states
      via defective boundaries.
AB  - One of the most severe limits of graphene nanoribbons (GNRs) in future
      applications is that zigzag GNRs (ZGNRs) are gapless, so cannot be used in field
      effect transistors (FETs), and armchair GNR (AGNR) based FETs require atomically
      precise control of edges and width. Using the tight-binding approach and first
      principles method, we derived and proved a general boundary condition for the
      opening of a significant bandgap in ZGNRs with defective edge structures. The
      proposed semiconducting ZGNRs have some interesting properties one of which is
      that they can be embedded and integrated in a large piece of graphene without the
      need to completely cut them out. We also demonstrated a new type of high
      performance all-ZGNR FET. Previous proposals of graphene FETs are all based on
      AGNRs.

PMID- 21967830
TI  - Design, rationale, and baseline characteristics of a cluster randomized
      controlled trial of pay for performance for hypertension treatment: study
      protocol.
AB  - BACKGROUND: Despite compelling evidence of the benefits of treatment and well
      accepted guidelines for treatment, hypertension is controlled in less than one
      half of United States citizens. METHODS/DESIGN: This randomized controlled trial
      tests whether explicit financial incentives promote the translation of guideline
      recommended care for hypertension into clinical practice and improve blood
      pressure (BP) control in the primary care setting. Using constrained
      randomization, we assigned 12 Veterans Affairs hospital outpatient clinics to
      four study arms: physician-level incentive; group-level incentive; combination of
      physician and group incentives; and no incentives (control). All participants at
      the hospital (cluster) were assigned to the same study arm. We enrolled 83 full
      time primary care physicians and 42 non-physician personnel. The intervention
      consisted of an educational session about guideline-recommended care for
      hypertension, five audit and feedback reports, and five disbursements of
      incentive payments. Incentive payments rewarded participants for chart-documented
      use of guideline-recommended antihypertensive medications, BP control, and
      appropriate responses to uncontrolled BP during a prior four-month performance
      period over the 20-month intervention. To identify potential unintended
      consequences of the incentives, the study team interviewed study participants, as
      well as non-participant primary care personnel and leadership at study sites.
      Chart reviews included data collection on quality measures not related to
      hypertension. To evaluate the persistence of the effect of the incentives, the
      study design includes a washout period. DISCUSSION: We briefly describe the
      rationale for the interventions being studied, as well as the major design
      choices. Rigorous research designs such as the one described here are necessary
      to determine whether performance-based payment arrangements such as financial
      incentives result in meaningful quality improvements. TRIAL REGISTRATION:
      http://www.clinicaltrials.govNCT00302718.

PMID- 21967831
TI  - Time changes in predictive power of established and recently proposed clinical,
      cytogenetical and comorbidity scores for Myelodysplastic Syndromes.
AB  - BACKGROUND: Recent improvements in the treatment of Myelodysplastic Syndromes
      have fostered further interest in the development of prognostic scores.
      Prognostic indices such as the IPSS were developed and later validated assuming
      their predictive values to be unchanged over time. A systematic analysis of the
      possible variability of predictive power over time in different scores is still
      lacking and was the aim of this study. DESIGN AND METHODS: For 243 primary MDS
      patients from a single institution treated with supportive care, 19 established
      or modified scoring systems based on different prognostic factors (clinical,
      cytogenetical and/or comorbidity) were analysed for their variability over time
      by statistical methods that quantify time variations in the risk relations
      (specifically the risk ratios of Cox models) between prognostic subgroups.
      RESULTS: Established scores based mainly on clinical parameters showed strong to
      moderate loss of predictive power over time whereas cytogenetic scores maintained
      their predictive power. Scores including comorbidity data showed gain of
      predictive power over time. CONCLUSIONS: The development and comparison of
      prognostic systems have to take into account their stability versus the
      possibility or need for re-evaluation. Possibly not only re-evaluation after time
      is of importance, but also different weighting of items constituting scores.

PMID- 21967832
TI  - WT1 expression as a marker of minimal residual disease predicts outcome in acute
      myeloid leukemia when measured post-consolidation.
AB  - WT1 levels may be a useful predictor of leukemia free survival (LFS) following
      treatment of acute myeloid leukemia (AML). We report a retrospective study in
      which levels of WT1 expression from patients with de novo AML were measured from
      bone marrow and peripheral blood at diagnosis, post-induction, post-consolidation
      and relapse. We demonstrate that higher levels of WT1 in peripheral blood at
      diagnosis are associated with poorer LFS independent of age and cytogenetic risk
      group (n=85, p=0.028). When measured at post-consolidation, the presence of
      detectable WT1 is associated with poorer LFS in univariate analysis of both
      peripheral blood (p=0.024) and bone marrow (p=0.019). In a multivariate analysis
      including age and cytogenetic risk, the association remained significant for bone
      marrow (p=0.016) with a trend observed for peripheral blood (p=0.06). These
      findings have formed the basis for ongoing research.

PMID- 21967833
TI  - Administration of edaravone, a free radical scavenger, during t-PA infusion can
      enhance early recanalization in acute stroke patients--a preliminary study.
AB  - BACKGROUND AND PURPOSE: The aim of the present study was to investigate whether
      administration of edaravone during t-PA infusion can enhance early recanalization
      in acute stroke patients. METHODS: This trial was undertaken as a multicenter,
      single blind, randomized, open-labeled study. Acute stroke patients with M1 or M2
      occlusion within 3h of onset were studied prospectively. The subjects were
      randomly allocated to edaravone (Edaravone group: when t-PA was intravenously
      infused, intravenous edaravone (30 mg) was started at the same time) and no
      edaravone (Non-Edaravone group). Early recanalization within 1h after t-PA
      infusion and neurological recovery 24h after t-PA infusion were compared between
      the two groups. RESULTS: 40 patients (23 men, 17 women; mean age, 76.4 +/- 8.2
      years, median 79 years) were enrolled; 23 patients were assigned to the Edaravone
      group and 17 to the Non-Edaravone group. Early recanalization was more frequently
      observed in the Edaravone group than in the Non-Edaravone group (56.5% vs. 11.8%,
      P=0.0072). Eight patients who underwent endovascular therapy immediately after t
      PA infusion were excluded, and neurological recovery was analyzed. Remarkable and
      good recoveries were more frequently observed in the Edaravone group than in the
      Non-Edaravone group (80.1% vs. 45.5%, P=0.0396). CONCLUSION: Early recanalization
      and good neurological recovery were more frequently observed in the Edaravone
      group than in the Non-Edaravone group. These results demonstrate that
      administration of edaravone during t-PA infusion should enhance early
      recanalization in acute stroke patients.

PMID- 21967834
TI  - Peroxidation of lipoproteins in multiple sclerosis.
AB  - Human plasma low density lipoproteins (LDL) and high density lipoproteins (HDL)
      are involved in the transport of lipids, modulate membrane lipid composition and
      regulate signal transduction. HDL-like lipoproteins have been shown also in human
      cerebrospinal fluid and it has been hypothesized that they could have a role in
      lipid transport in central nervous system. After synthesis, lipoproteins are
      susceptible to lipid peroxidation triggered by reactive oxygen species (ROS and
      RNS) produced by peripheral and brain cells. Aim of the paper has been to review
      the scientific literature on the role of lipid peroxidation of LDL and HDL in the
      molecular mechanisms of multiple sclerosis (MS). Several studies have
      demonstrated a significant increase in lipid peroxidation products in brain,
      plasma and cerebrospinal fluid of MS patients. The increase of antibodies against
      ox-LDL in plasma and the presence of ox-LDL in demyelinating plaques in MS brain
      suggests that the disease is associated with oxidative damage of lipoproteins.
      The impairment of antioxidant systems or an increase in the production of ROS and
      RNS could contribute to lipoprotein peroxidation in MS. Oxidized lipoproteins
      show several alterations of their functions, they are neurotoxic and have pro
      inflammatory properties. Therefore lipoprotein lipid peroxidation products could
      be involved in demyelination and axonal injury in MS.

PMID- 21967836
TI  - Microcosm biofilms originating from children with different caries experience
      have similar cariogenicity under successive sucrose challenges.
AB  - OBJECTIVES: The source of saliva inocula and the individual characteristics of
      saliva donors could affect the cariogenic activity of in vitro biofilms, but this
      could also be modulated by environmental determinants, such as the frequency of
      sugar consumption. Therefore, the aim of this study was to compare the
      cariogenicity of microcosm biofilm growths from the saliva of caries-free (CF)
      children, children with early childhood caries (ECC) and with severe ECC (S-ECC),
      under regular sucrose exposure. METHODS: Microcosm plaque biofilms were initiated
      from the saliva of CF, ECC and S-ECC children. Biofilms were grown in 24-well
      microplates on bovine enamel discs for up to 10 days in artificial saliva, which
      was replaced daily. Growth conditions comprised cariogenic challenge (artificial
      saliva supplemented with 1% sucrose 6 h/day) or no cariogenic challenge. Daily pH
      was obtained from the artificial saliva, and after the experimental period, the
      biofilm formed on the enamel discs was collected for microbiological analyses.
      Mineral loss in enamel discs was estimated by percentage of surface hardness
      change. RESULTS: Overall, no statistically significant differences were found
      among saliva sources (p > 0.05). Streptococcus mutans and lactobacilli counts
      increased in the biofilms grown under cariogenic challenge (p < 0.05), while a
      substantial decrease in the artificial saliva pH was detected under the same
      condition (p < 0.001). Higher demineralization (p < 0.001) was observed under
      sucrose exposure regardless of caries experience of children. CONCLUSIONS: While
      the sucrose exposure determined the cariogenicity of the biofilms, the caries
      experience of children who provided the inocula did not affect mineral loss
      associated with these biofilms.

PMID- 21967835
TI  - The KCNE genes in hypertrophic cardiomyopathy: a candidate gene study.
AB  - BACKGROUND: The gene family KCNE1-5, which encode modulating beta-subunits of
      several repolarising K+-ion channels, has been associated with genetic cardiac
      diseases such as long QT syndrome, atrial fibrillation and Brugada syndrome. The
      minK peptide, encoded by KCNE1, is attached to the Z-disc of the sarcomere as
      well as the T-tubules of the sarcolemma. It has been suggested that minK forms
      part of an "electro-mechanical feed-back" which links cardiomyocyte stretching to
      changes in ion channel function. We examined whether mutations in KCNE genes were
      associated with hypertrophic cardiomyopathy (HCM), a genetic disease associated
      with an improper hypertrophic response. RESULTS: The coding regions of KCNE1,
      KCNE2, KCNE3, KCNE4, and KCNE5 were examined, by direct DNA sequencing, in a
      cohort of 93 unrelated HCM probands and 188 blood donor controls.Fifteen genetic
      variants, four previously unknown, were identified in the HCM probands. Eight
      variants were non-synonymous and one was located in the 3'UTR-region of KCNE4. No
      disease-causing mutations were found and no significant difference in the
      frequency of genetic variants was found between HCM probands and controls. Two
      variants of likely functional significance were found in controls only.
      CONCLUSIONS: Mutations in KCNE genes are not a common cause of HCM and
      polymorphisms in these genes do not seem to be associated with a propensity to
      develop arrhythmia.

PMID- 21967837
TI  - Increased patient information does not reduce patient anxiety regarding
      urodynamic studies.
AB  - OBJECTIVE: To establish if patient anxiety pre-urodynamic investigation can be
      reduced by providing more information within the patient information sheet (PIS).
      PATIENTS AND METHODS: Two prospective cohorts of consecutive patients (round 1, n
      = 98 and round 2, n = 94) were asked to complete a visual analogue scale (VAS)
      quantifying their anxiety prior to urodynamics (UDS) and again after UDS
      quantifying their anxiety of potentially repeating UDS. Patients in round 1
      received the standard hospital PIS. Concurrently with round 1, a parallel group
      of patients (n = 95) completed a questionnaire regarding their experience of UDS
      and their post-UDS complications. This information was incorporated into a
      revised PIS used in round 2. RESULTS: In both rounds, the VAS reduced post-UDS
      (Wilcoxon matched-pairs test p < 0.001). In females, pre-UDS VAS was
      significantly higher in round 2 than round 1 (Mann-Whitney U test p = 0.037). In
      males, pre-UDS VAS was lower in round 2 than round 1, but this difference was not
      statistically significant (Mann-Whitney U test p = 0.112). Post-UDS VAS was
      remarkably similar between round 1 and 2. CONCLUSIONS: Patients are less anxious
      about having repeat UDS regardless of the depth of information provided. However,
      more detailed information before UDS failed to significantly reduce patient
      anxiety.

PMID- 21967838
TI  - Fine structure of myotendinous junction between the anterior belly of the
      digastric muscle and intermediate tendon in adults rats.
AB  - This study analyzed the ultrastructural characteristics of the myotendinous
      junction (MTJ) between anterior belly of digastrics muscle and the intermediate
      tendon in adult rats. Six male Wistar rats were used and were anesthetized with
      an overdose of urethane and sacrificed by intracardiac perfusion with modified
      Karnovsky solution, postfixed in 1% osmium tetroxide, dehydrated in increasing
      series of alcohols and embedded in Spurr resin for transmission electron
      microscopic analysis. Ultrastructural analysis showed conical shape of the fiber
      extremity in MTJ region, highlighting the presence of numerous mitochondria
      arranged in groups in the subsarcolemmal and intermyofibrillary regions. Atypical
      MTJ characteristics were seen interspersed with bundles of collagen fibers.
      Classic characteristics such as finger-like processes by means of sarcoplasmic
      projections were observed among interdigitations. Terminals and periphericals
      bundles of myofibrils showed close relationship with the adjacent muscle fiber's
      endomysium through lateral junctions. In the distal portion, it was observed that
      the communication region of microtendons forming the intermediate tendon of
      digastric muscle, and it can highlight the columns disposition of tenocytes. In
      conclusion, the MTJ ultrastructure between the anterior belly of digastric muscle
      and intermediate tendon of adult rats showed classical morphologic descriptions
      and presented an atypical region revealed by the subspecialization between the
      myofibrils bundles and collagen fibers in the MTJ region.

PMID- 21967839
TI  - EMF recommendations specific for children?
AB  - When discussing health risks for children due to electromagnetic fields it is
      crucial to translate scientific knowledge both into adequate protection and
      precautionary measures for the general public and, more particularly into
      specific recommendations for children. It is often aimed at influencing health
      related attitudes and behaviour by means of information about health affecting
      behaviour, health risk factors, and health promoting possibilities. Children have
      to be treated differently from adults in addressing their ability and willingness
      to modify behaviour and their competence to comprehend cognitively the sense of
      behavioural recommendations. Research has shown that adults can be motivated to
      adjust their own behaviour in order to protect their children or to be role
      models for their children. Hence one way to modify children's behaviour is to
      address the parents and care persons. Generally education in the family, the
      social environment and in peer groups, nursery school and at school plays an
      important role in forming and influencing individual behaviour. The age of the
      target group has also to be taken into consideration. An important question is
      how to deal with scientific uncertainties when expressing EMF recommendations for
      children. Accentuating scientific uncertainties may under certain circumstances
      raise risk awareness. This can be an intended effect. But the expression of
      scientific uncertainties can also lead to unintended consequences in parent's
      behaviour or even senseless dealing with the respective EMF source. The paper
      points out relevant aspects of risk communication regarding EMF and children and
      suggests how recommendations for children might be designed.

PMID- 21967840
TI  - Prevalence of methicillin-resistant Staphylococcus aureus colonization in
      emergency medical service providers.

PMID- 21967841
TI  - The effect of folic acid as an antioxidant on the hypothalamic monoamines in
      experimentally induced hypothyroid rat.
AB  - Thyroid hormones are recognized as key metabolic hormones that play a critical
      role in the central nervous system development throughout life. In the present
      study, we studied the biochemical changes of hypothalamus of hypothyroid rats at
      post-pubertal stage, and the possible ameliorating effect of folic acid. A total
      of 50 male albino rats were equally divided into five groups; the first and
      second groups were the control and folic acid groups, respectively, while the
      third group was the hypothyroid group in which rats received daily 6-n-propyl-2
      thiouracil (PTU) in drinking water for 6 weeks to induce hypothyroidism. The
      fourth and fifth groups were hypothyroid rats treated with folic acid for 4 weeks
      during and after receiving PTU, respectively, and were dissected after 6 and 10
      weeks, respectively. There was a significant increase in plasma total
      homocysteine, malondialdehyde (MDA), oxidized glutathione?reduced glutathione and
      total nitric oxide and hypothalamic MDA, serotonin and norepinephrine in the
      hypothyroid rats group as compared to the control group. This reflects
      hyperhomocysteinaemia and oxidative stress associated with hypothyroid state. On
      the other hand, hypothalamic total nitric oxide and dopamine in the hypothyroid
      rats group were significantly decreased when compared to the control group.
      Treatment of hypothyroid rats with folic acid improves the oxidative stress and
      hypothalamic monoamines. Our results revealed that, folic acid treatment was
      better if it is administered as an adjuvant after returning to the euthyroid
      state.

PMID- 21967842
TI  - Protective properties of five newly synthesized cyclic compounds against sodium
      azide and N-methyl-N'-nitro-N-nitrosoguanidine genotoxicity.
AB  - The current study aims to determine the antimutagenic potential of five newly
      synthesized cyclic compounds against the genotoxic agents sodium azide (NaN3) and
      N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The mutant bacterial tester strains
      were NaN3-sensitive Salmonella typhimurium TA1535 and MNNG-sensitive Escherichia
      coli WP2uvrA. According to the results, all the test compounds showed significant
      antimutagenic activity. The inhibition rates ranged from 26.05% (Compound 4-1
      ug/plate) to 68.54% (Compound 5-0.01 ug/plate) for NaN3 and from 32.44% (Compound
      3-1 ug/plate) to 60.77% (Compound 5-1 ug/plate) for MNNG genotoxicity. Moreover,
      the mutagenic potential of the test compounds was investigated using the same
      strains. The results showed that all the test compounds do not have mutagenic
      potential on the bacterial strains at the tested concentrations. Thus, the
      findings of the present study give valuable information about chemical prevention
      from NaN3 and MNNG genotoxicity.

PMID- 21967843
TI  - The effect of vitamin E on pathological changes in kidney and liver of sulphur
      mustard-exposed guinea pigs.
AB  - Sulphur mustard (SM) gas is a poisonous chemical agent causing various systemic
      action in laboratory animals. There is no definite treatment for disorders
      induced by SM. In this study, the effect of vitamin E alone and in combination
      with dexamethasone on the pathological changes in the kidney and liver of SM
      exposed (SME) guinea pigs was examined. Guinea pigs were divided into five groups
      (n = 5 in each). These groups were exposed to ethanol (control group), 100
      mg/m(3) inhaled SM (SME group), SME treated with vitamin E, 600 mg/kg (SME + E),
      SME treated with dexamethasone, 5 mg/kg (SME + D), and SME treated with both
      drugs (SME + E + D), respectively. Pathological evaluation of the kidneys and
      livers was done 14 days post exposure. There were statistically significant
      pathological changes in the liver and kidney of SME group compared to control
      animals (p < 0.05 to p < 0.001). Treatment of SME animals with vitamin E,
      dexamethasone and their combination caused statistically significant improvement
      in the pathological changes in the livers and kidneys (p < 0.05 to p < 0.001).
      These results showed a preventive effect of vitamin E on pathological changes in
      the liver and more prominently in the kidneys of SME guinea pigs.

PMID- 21967844
TI  - Antiretroviral drug supply challenges in the era of scaling up ART in Malawi.
AB  - The number of people receiving antiretroviral treatment (ART) has increased
      considerably in recent years and is expected to continue to grow in the coming
      years. A major challenge is to maintain uninterrupted supplies of antiretroviral
      (ARV) drugs and prevent stock outs. This article discusses issues around the
      management of ARVs and prevention of stock outs in Malawi, a low-income country
      with a high HIV/AIDS burden, and a weak procurement and supply chain management
      system. This system for ARVs, paid for by the Global Fund to Fight AIDS,
      Tuberculosis and Malaria, and bypassing the government Central Medical Stores, is
      in place, using the United Nations Children's Fund's (UNICEF's) procurement
      services. The system, managed by a handful of people who spend limited time on
      supply management, is characterized by a centrally coordinated quantification
      based on verified data from all national ART clinics, parallel procurement
      through UNICEF, and direct distribution to ART clinics. The model worked well in
      the first years of the ART programme with a single first-line ARV regimen, but
      with more regimens becoming available (e.g., alternative first-line, second-line
      and paediatric regimens), it has become more difficult to administer. Managing
      supplies through a parallel system has the advantage that weaknesses in the
      national system have limited influence on the ARV procurement and supply chain
      management system. However, as the current system operates without a central
      warehouse and national buffer stock capacity, it diminishes the ability to
      prevent ARV stock outs. The process of ordering ARVs, from the time that
      estimates are made to the arrival of supplies in health facilities, takes
      approximately one year. Addressing the challenges involved in maintaining ARVs
      through an efficient procurement and supply chain management system that prevents
      ARV stock outs through the establishment of a dedicated procurement team, a
      central warehouse and/or national buffer stock is a priority.

PMID- 21967845
TI  - Effects of n-3 fatty acids on cognitive decline: a randomized, double-blind,
      placebo-controlled trial in stable myocardial infarction patients.
AB  - BACKGROUND: Epidemiological studies suggest a protective effect of n-3 fatty
      acids derived from fish (eicosapentaenoic acid [EPA] and docosahexaenoic acid
      [DHA]) against cognitive decline. For alpha-linolenic acid (ALA) obtained from
      vegetable sources, the effect on cognitive decline is unknown. We examined the
      effect of n-3 fatty acid supplementation on cognitive decline in coronary heart
      disease patients. METHODS: The analysis included 2911 coronary patients (78% men)
      aged 60 to 80 years who participated in a double-blind placebo-controlled trial
      of n-3 fatty acids and cardiovascular diseases (Alpha Omega Trial). By using a 2
      * 2 factorial design, patients were randomly assigned to margarines that provided
      400 mg/d of EPA-DHA, 2 g/d of ALA, both EPA-DHA and ALA, or placebo for 40
      months. Cognitive function was assessed by the Mini-Mental State Examination
      (MMSE) at baseline and after 40 months. The effect of n-3 fatty acids on change
      in MMSE score was assessed using analysis of variance. Logistic regression
      analysis was used to examine the effects on risk of cognitive decline, defined as
      a decrease of 3 or more points in MMSE score or incidence of dementia. RESULTS:
      Patients in the active treatment groups had an additional intake of 384 mg of EPA
      DHA, 1.9 g of ALA, or both. The overall MMSE score in this cohort was 28.3 +/-
      1.6 points, which decreased by 0.67 +/- 2.25 points during follow-up. Changes in
      MMSE score during intervention did not differ significantly between EPA-DHA and
      placebo (-0.65 vs -0.69 points, P = .44) or between ALA and placebo (-0.60 vs 
      0.74 points, P = .12). The risk of cognitive decline was 1.03 (95% confidence
      interval: 0.84-1.26, P = .80) for EPA-DHA (vs placebo) and 0.90 (0.74-1.10, P =
      .31) for ALA (vs placebo). CONCLUSION: This large intervention study showed no
      effect of dietary doses of n-3 fatty acids on global cognitive decline in
      coronary heart disease patients.

PMID- 21967846
TI  - Improvement of the detection of neurodegenerative Alzheimer's disease through a
      specific surface chemistry applied onto the inner surface of the titration well.
AB  - The main objective of this paper was to illustrate the enhancement of the
      sensitivity of the ELISA titration of Tau proteins while reducing other non
      specific adsorptions that could increase the optical densities and could lead to
      false positives. This goal was obtained thanks to the association of cold plasma
      and wet chemistries of the inner surface of the titration well. The PP surface
      was cold plasma-activated, then coated with different amphiphilic molecules
      bearing either ionic charges and/or long hydrocarbon chains. The support treated
      and coated with hexatrimethylammonium bromide improves the signal detection of
      proteins while reducing the background due to non-specific associations of
      biomolecules such as hyperphosphorylated Tau protein. However, coating with 3
      butenylamine hydrochloride could also be suitable. 

PMID- 21967847
TI  - The acetylation of transcription factor HBP1 by p300/CBP enhances p16INK4A
      expression.
AB  - HBP1 is a sequence-specific DNA-binding transcription factor with many important
      biological roles. It activates or represses the expression of some specific genes
      during cell growth and differentiation. Previous studies have exhibited that HBP1
      binds to p16(INK4A) promoter and activates p16(INK4A) expression. We found that
      trichostatin A (TSA), an inhibitor of HDAC (histone deacetylase), induces
      p16(INK4A) expression in an HBP1-dependent manner. This result was drawn from a
      transactivation experiment by measuring relative luciferase activities of
      p16(INK4A) promoter with HBP1-binding site in comparison with that of the wild
      type p16(INK4A) promoter by transient cotransfection with HBP1 into HEK293T cells
      and 2BS cells. HBP1 acetylation after TSA treatment was confirmed by
      immunoprecipitation assay. Our data showed that HBP1 interacted with histone
      acetyltransferase p300 and CREB-binding protein (CBP) and also recruited p300/CBP
      to p16(INK4A) promoter. HBP1 was acetylated by p300/CBP in two regions:
      repression domain (K297/305/307) and P domain (K171/419). Acetylation of
      Repression domain was not required for HBP1 transactivation on p16(INK4A).
      However, luciferase assay and western blotting results indicate that acetylation
      of P domain, especially K419 acetylation is essential for HBP1 transactivation on
      p16(INK4A). As assayed by SA-beta-gal staining, the acetylation of HBP1 at K419
      enhanced HBP1-induced premature senescence in 2BS cells. In addition, HDAC4
      repressed HBP1-induced premature senescence through permanently deacetylating
      HBP1. We conclude that our data suggest that HBP1 acetylation at K419 plays an
      important role in HBP1-induced p16(INK4A) expression.

PMID- 21967848
TI  - Asymmetric nature of two subunits of RAD18, a RING-type ubiquitin ligase E3, in
      the human RAD6A-RAD18 ternary complex.
AB  - RAD18, a RING-type ubiquitin ligase (E3) that plays an essential role in post
      replication repair, possesses distinct domains named RING, UBZ, SAP and the RAD6
      binding domain (R6BD) and forms a dimer. RAD6, an ubiquitin-conjugating enzyme
      (E2), stably associates with R6BD in the C-terminal portion. In this study, we
      established a method to distinguish between the two subunits of RAD18 by
      introduction of different tags, and analyzed mutant complexes. Our results,
      surprisingly, demonstrate that RAD6A and RAD18 form a ternary complex, RAD6A
      (RAD18)(2) and the presence of only one R6BD in the two RAD18 subunits is
      sufficient for ternary complex formation and the ligase activity. Interestingly,
      ligase activity of a mutant dimer lacking both R6BDs is not restored even with
      large amounts of RAD6A added in solution, suggesting a requirement for precise
      juxtaposition via interaction with R6BD. We further show that mutations in both
      subunits of either RING or SAP, but not UBZ, strongly reduce ligase activity,
      although inactivation in only one of two subunits is without effect. These
      results suggest an asymmetric nature of the two RAD18 subunits in the complex.

PMID- 21967849
TI  - Luminescent detection of DNA-binding proteins.
AB  - Transcription factors play a central role in cell development, differentiation
      and growth in biological systems due to their ability to regulate gene expression
      by binding to specific DNA sequences within the nucleus. The dysregulation of
      transcription factor signaling has been implicated in the pathogenesis of a
      number of cancers, developmental disorders, inflammation and autoimmunity. There
      is thus a high demand for convenient high-throughput methodologies able to detect
      sequence-specific DNA-binding proteins and monitor their DNA-binding activities.
      Traditional approaches for protein detection include gel mobility shift assays,
      DNA footprinting and enzyme-linked immunosorbent assays (ELISAs) which tend to be
      tedious, time-consuming, and may necessitate the use of radiographic labeling. By
      contrast, luminescence technologies offer the potential for rapid, sensitive and
      low-cost detection that are amenable to high-throughput and real-time analysis.
      The discoveries of molecular beacons and aptamers have spear-headed the
      development of new luminescent methodologies for the detection of proteins over
      the last decade. We survey here recent advances in the development of luminescent
      detection methods for DNA-binding proteins, including those based on molecular
      beacons, aptamer beacons, label-free techniques and exonuclease protection.

PMID- 21967850
TI  - Experimental identification and analysis of macronuclear non-coding RNAs from the
      ciliate Tetrahymena thermophila.
AB  - The ciliate Tetrahymena thermophila is an important eukaryotic model organism
      that has been used in pioneering studies of general phenomena, such as ribozymes,
      telomeres, chromatin structure and genome reorganization. Recent work has shown
      that Tetrahymena has many classes of small RNA molecules expressed during
      vegetative growth or sexual reorganization. In order to get an overview of medium
      sized (40-500 nt) RNAs expressed from the Tetrahymena genome, we created a size
      fractionated cDNA library from macronuclear RNA and analyzed 80 RNAs, most of
      which were previously unknown. The most abundant class was small nucleolar RNAs
      (snoRNAs), many of which are formed by an unusual maturation pathway. The
      modifications guided by the snoRNAs were analyzed bioinformatically and
      experimentally and many Tetrahymena-specific modifications were found, including
      several in an essential, but not conserved domain of ribosomal RNA. Of particular
      interest, we detected two methylations in the 5'-end of U6 small nuclear RNA
      (snRNA) that has an unusual structure in Tetrahymena. Further, we found a
      candidate for the first U8 outside metazoans, and an unusual U14 candidate. In
      addition, a number of candidates for new non-coding RNAs were characterized by
      expression analysis at different growth conditions.

PMID- 21967851
TI  - Manipulating the proximal triad His-Asn-Arg in human myeloperoxidase.
AB  - In mammalian peroxidases the proximal histidine is in close interaction with a
      fully conserved asparagine which in turn is hydrogen bonded with an arginine that
      stabilizes the propionate substituent of pyrrol ring D in bent conformation. In
      order to probe the role of this rigid proximal architecture for structural
      integrity and catalysis of human myeloperoxidase (MPO), the variants Asn421Asp,
      Arg333Ala and Arg333Lys have been recombinantly expressed in HEK cell lines. The
      standard reduction potential of the Fe(III)/Fe(II) couple of Asn421Asp was still
      wild-type-like (-50mV at pH 7.0) but the spectral properties of the ferric and
      ferrous forms as well as of higher oxidation states showed significant
      differences. Additionally, rates of ligand binding and oxidation of both one- and
      two-electron donors were diminished. The effect of exchange of Arg333 was even
      more dramatic. We did not succeed in production of mutant proteins that could
      bind heme at the active site. The importance of this His-Asn-Arg triad in linking
      the heme iron with the propionate at pyrrol ring D for heme insertion and binding
      as well as in maintenance of the architecture of the substrate binding site(s) at
      the entrance to the heme cavity is discussed.

PMID- 21967852
TI  - TNIP1 is a corepressor of agonist-bound PPARs.
AB  - Nuclear receptor (NR) coregulators include coactivators, contributing to
      holoreceptor transcriptional activity, and corepressors, mediating NR target gene
      silencing in the absence of hormone. We identified an atypical NR coregulator,
      TNFalpha-induced protein 3-interacting protein 1 (TNIP1), from a peroxisome
      proliferator activated receptor (PPAR) alpha screen of a human keratinocyte cDNA
      library. TNIP1's complex nomenclature parallels its additional function as an NF
      kappaB inhibitor. Here we show TNIP1 is an atypical NR corepressor using two
      hybrid systems, biochemical studies, and receptor activity assays. The
      requirements for TNIP1-PPAR interaction are characteristic for coactivators;
      however, TNIP1 partially decreases PPAR activity. TNIP1 has separable
      transcriptional activation and repression domains suggesting a modular nature to
      its overall effect. It may provide a means of lowering receptor activity in the
      presence of ligand without total loss of receptor function. TNIP1's multiple
      roles and expression in several cell types suggest its regulatory effect depends
      on its expression level and the expression of other regulators in NR and/or NF
      kappaB signaling pathways. As a NR coregulator, TNIP1 targeting agonist-bound
      PPAR and reducing transcriptional activity offers control of receptor signaling
      not available from typical corepressors and may contribute to combinatorial
      regulation of transcription.

PMID- 21967853
TI  - Cortisol responses to emotional stress in men: association with a functional
      polymorphism in the 5HTR2C gene.
AB  - The serotonin 5HTR2C receptor has been shown to mediate HPA axis activation
      during stress. We hypothesized that a functional polymorphism (rs6318) of the
      5HTR2C gene would be associated with HPA axis response to a laboratory stress
      protocol. The present sample consisted of 41 men (22 African Americans, 19
      Caucasians). We found that at rest men with the more active rs6318 Ser23 C allele
      had similar cortisol values compared to those with the less active Cys23 G
      allele. During laboratory stress, however, men with the Ser23 C allele exhibited
      the predicted significantly higher cortisol levels (p<0.001), as well as larger
      increases in anger (p=0.08) and depressive mood (p=0.006) ratings, compared to
      the Cys23 G carriers. The increase in cortisol was significantly related to the
      increases in ratings of anger and depression assessed before and after the
      emotion induction, and these correlations became nonsignificant when rs6318
      genotype was covaried. We conclude that genetic variation in 5HTR2C may be
      associated with HPA axis activation and stimulated by emotional stress, and also
      with both psychological and physiological endophenotypes that increase the risk
      of cardiovascular disease and type-2 diabetes.

PMID- 21967854
TI  - Preliminary evidence that acute long-chain omega-3 supplementation reduces
      cardiovascular reactivity to mental stress: a randomized and placebo controlled
      trial.
AB  - OBJECTIVE: Exaggerated cardiovascular reactivity predicts cardiovascular
      morbidity and mortality. Some evidence suggests that omega-3 fatty acids improve
      cardiovascular function. The objective of this study was to examine the influence
      of an acute low dose of long-chain omega-3 fatty acids on young, healthy
      individuals. METHODS: Participants (n=34) were randomly assigned to either 21
      days of omega-3 fatty acids (1.4 g EPA and DHA) or matched placebo.
      Cardiovascular measurements were obtained in the laboratory during baseline and
      during a standard mental arithmetic task, where participants were instructed to
      engage in serial subtractions by 17s from a four-digit number and cardiovascular
      reactivity to the task was calculated. RESULTS: Mean arterial pressure reactivity
      was significantly reduced by supplementation (F(1,32)=5. 12, p=.03, eta(2)=.144)
      but not by placebo. CONCLUSION: Supplementation of omega-3 fatty acids may reduce
      cardiovascular reactivity to stress.

PMID- 21967856
TI  - Specific prebiotics in a formula for infants with Phenylketonuria.
AB  - OBJECTIVE: This exploratory study investigated the influence of adding a
      patented, specific mixture of prebiotic oligosaccharides (scGOS/lcFOS [9:1
      ratio], Danone Research) to a protein substitute suitable for infants with
      Phenylketonuria (PKU); PKU Anamix Infant (Nutricia). DESIGN: This was an 8-week
      open-label, single-arm, pilot intervention study in 9 infants (8-week median age)
      diagnosed with PKU. On study entry, infants were prescribed PKU Anamix Infant to
      replace an infant phenylalanine-free protein substitute without prebiotics (IPS).
      Blood phenylalanine concentrations were monitored and stool samples analyzed for
      pH/bacterial groups. RESULTS: PKU Anamix infant was well tolerated and accepted
      with no adverse events reported. Overall, plasma phenylalanine and tyrosine
      concentrations were maintained within target ranges throughout the study (120-360
      MUmol/l phenylalanine, 30-100 MUmol/l tyrosine). All infants exhibited microbiota
      dominated by bifidobacteria (median 58.97% at Week 8), although no statistically
      significant change from baseline was observed at study endpoint. No infants
      showed abnormally high levels of Clostridium histolyticum/lituseburense or
      potentially pathogenic enterobacteriaceae at any point during the study. A
      significant reduction in median stool pH versus baseline was observed at Week 4
      (pH reduced from 6.79 to 5.83), but this significance was not present at Week 8
      (pH = 6.61). CONCLUSIONS: PKU Anamix Infant maintains phenylalanine control in
      line with established IPS without prebiotics and maintains levels of
      bifidobacteria and lowers stool pH. In exclusively breast-fed infants the latter
      two factors have been associated with a reduced risk of infection and may be of
      particular importance in infants with PKU.

PMID- 21967855
TI  - Thought suppression, impaired regulation of urges, and Addiction-Stroop predict
      affect-modulated cue-reactivity among alcohol dependent adults.
AB  - Abstinent alcohol dependent individuals commonly employ thought suppression to
      cope with stress and intrusive cognitions about alcohol. This strategy may
      inadvertently bias attention towards alcohol-related stimuli while depleting
      neurocognitive resources needed to regulate urges, manifested as decreased heart
      rate variability (HRV) responsivity to alcohol cues. The present study tested the
      hypothesis that trait and state thought suppression, impaired regulation of
      urges, and alcohol attentional bias as measured by the Addiction-Stroop would
      have significant effects on the HRV responsivity of 58 adults in residential
      treatment for alcohol dependence (mean age=39.6 +/- 9.4, 81% female) who
      participated in an affect-modulated cue-reactivity protocol. Regression analyses
      controlling for age, level of pre-treatment alcohol consumption, and baseline HRV
      indicated that higher levels of trait thought suppression, impaired regulation of
      alcohol urges, and attentional fixation on alcohol cues were associated with
      lower HRV responsivity during stress-primed alcohol cue-exposure. Moreover, there
      was a significant state * trait suppression interaction on HRV cue-responsivity,
      such that alcohol dependent persons reporting high levels of state and trait
      suppression exhibited less HRV during cue-exposure than persons reporting low
      levels of state and trait suppression. Results suggest that chronic thought
      suppression taxes regulatory resources reflected in reduced HRV responsivity, an
      effect that is particularly evident when high trait suppressors engage in
      intensive suppression of drinking-related thoughts under conditions of stress.
      Treatment approaches that offer effective alternatives to the maladaptive
      strategy of suppressing alcohol urges may be crucial for relapse prevention.

PMID- 21967858
TI  - Tay-Sachs disease in an Arab family due to c.78G>A HEXA nonsense mutation
      encoding a p.W26X early truncation enzyme peptide.
AB  - Tay-Sachs disease (TSD), a pan-ethnic, autosomal recessive, neurodegenerative,
      lysosomal disease, results from deficient beta-hexosaminidase A activity due to
      beta-hexosaminidase alpha-subunit (HEXA) mutations. Prenatal/premarital carrier
      screening programs in the Ashkenazi Jewish community have markedly reduced
      disease occurrence. We report the first Jordanian Arab TSD patient diagnosed by
      deficient beta-hexosaminidase A activity. HEXA mutation analysis revealed
      homozygosity for a nonsense mutation, c.78G>A (p.W26X). Previously reported in
      Arab patients, this mutation is a candidate for TSD screening in Arab
      populations.

PMID- 21967857
TI  - Up to date knowledge on different treatment strategies for phenylketonuria.
AB  - Dietary management for phenylketonuria was established over half a century ago,
      and has rendered an immense success in the prevention of the severe mental
      retardation associated with the accumulation of phenylalanine. However, the
      strict low-phenylalanine diet has several shortcomings, not the least of which is
      the burden it imposes on the patients and their families consequently frequent
      dietary non-compliance. Imperfect neurological outcome of patients in comparison
      to non-PKU individuals and nutritional deficiencies associated to the PKU diet
      are other important reasons to seek alternative therapies. In the last decade
      there has been an impressive effort in the investigation of other ways to treat
      PKU that might improve the outcome and quality of life of these patients. These
      studies have lead to the commercialization of sapropterin dihydrochloride, but
      there are still many questions regarding which patients to challenge with
      sapropterin what is the best challenge protocol and what could be the
      implications of this treatment in the long-term. Current human trials of
      PEGylated phenylalanine ammonia lyase are underway, which might render an
      alternative to diet for those patients non-responsive to sapropterin
      dihydrochloride. Preclinical investigation of gene and cell therapies for PKU is
      ongoing. In this manuscript, we will review the current knowledge on novel
      pharmacologic approaches to the treatment of phenylketonuria.

PMID- 21967859
TI  - First experience with enzyme replacement therapy during pregnancy and lactation
      in Pompe disease.
AB  - Enzyme replacement therapy (ERT) with alglucosidase alfa was registered as a
      treatment for Pompe disease in 2006. It is as yet unknown whether ERT can be
      safely applied during pregnancy and lactation. A primiparous 40-year-old woman
      diagnosed with Pompe disease continued receiving ERT during pregnancy and
      lactation. Before pregnancy, she had moderate limb-girdle weakness and used
      nocturnal ventilation. During pregnancy, her clinical condition remained fairly
      stable until the 25th gestational week. Thereafter she experienced more problems
      with mobility and respiration. Fetal growth was normal as monitored by regular
      ultrasound investigations. A healthy boy was born at a gestational age of 37
      weeks and 5 days by elective Cesarean section. There were no maternal
      complications and the child developed normally. One year after delivery the
      mother's physical condition was similar as prior to her pregnancy.
      Pharmacokinetic studies following enzyme infusion showed that alglucosidase alfa
      was secreted into the breast milk. Activity levels in the milk (245 nmol/ml.h)
      peaked at 2.5h after the end of the infusion; which was 2h later than in the
      plasma (80 MUmol/ml.h). Twenty-four hours after start of the infusion, the enzyme
      activity in the breast milk was back to the pre-infusion level. In this case
      report, the continuation of treatment with alglucosidase alfa during pregnancy
      and lactation has been safe for the mother and the child.

PMID- 21967860
TI  - Stability of hydrogen incorporated in ZnO nanowires by plasma treatment.
AB  - The stability of hydrogen in ZnO is studied using hydrogenated nanowires by
      plasma treatment. Enhanced near band edge UV emission and reduced defect level
      green emission is observed after hydrogen plasma treatment. Through thermal
      stability tests, this effect is found to be stable at room temperature and nearly
      stable up to ~500 K, but begins to deteriorate at higher temperature. The study
      of the irradiation stability of the hydrogen in ZnO nanowires shows that the
      hydrogen is stable under an electron beam with an accelerating voltage lower than
      5 kV, but is not stable under 10 kV or under an intensive laser beam. The results
      could benefit the further understanding of the role of hydrogen in ZnO and light
      emitting devices based on hydrogenated ZnO.

PMID- 21967861
TI  - Differential chromatin proteomics of the MMS-induced DNA damage response in
      yeast.
AB  - BACKGROUND: Protein enrichment by sub-cellular fractionation was combined with
      differential-in-gel-electrophoresis (DIGE) to address the detection of the low
      abundance chromatin proteins in the budding yeast proteome. Comparisons of whole
      cell extracts and chromatin fractions were used to provide a measure of the
      degree of chromatin association for individual proteins, which could be compared
      across sample treatments. The method was applied to analyze the effect of the DNA
      damaging agent methyl methanesulfonate (MMS) on levels of chromatin-associated
      proteins. RESULTS: Up-regulation of several previously characterized DNA damage
      checkpoint-regulated proteins, such as Rnr4, Rpa1 and Rpa2, was observed. In
      addition, several novel DNA damage responsive proteins were identified and
      assessed for genotoxic sensitivity using either DAmP (decreased abundance by mRNA
      perturbation) or knockout strains, including Acf2, Arp3, Bmh1, Hsp31, Lsp1, Pst2,
      Rnr4, Rpa1, Rpa2, Ste4, Ycp4 and Yrb1. A strain in which the expression of the
      Ran-GTPase binding protein Yrb1 was reduced was found to be hypersensitive to
      genotoxic stress. CONCLUSION: The described method was effective at unveiling
      chromatin-associated proteins that are less likely to be detected in the absence
      of fractionation. Several novel proteins with altered chromatin abundance were
      identified including Yrb1, pointing to a role for this nuclear import associated
      protein in DNA damage response.

PMID- 21967862
TI  - Validity and usefulness of members reports of implementation progress in a
      quality improvement initiative: findings from the Team Check-up Tool (TCT).
AB  - BACKGROUND: Team-based interventions are effective for improving safety and
      quality of healthcare. However, contextual factors, such as team functioning,
      leadership, and organizational support, can vary significantly across teams and
      affect the level of implementation success. Yet, the science for measuring
      context is immature. The goal of this study is to validate measures from a short
      instrument tailored to track dynamic context and progress for a team-based
      quality improvement (QI) intervention. METHODS:  DESIGN: Secondary cross
      sectional and longitudinal analysis of data from a clustered randomized
      controlled trial (RCT) of a team-based quality improvement intervention to reduce
      central line-associated bloodstream infection (CLABSI) rates in intensive care
      units (ICUs). SETTING: Forty-six ICUs located within 35 faith-based, not-for
      profit community hospitals across 12 states in the U.S. POPULATION: Team members
      participating in an ICU-based QI intervention. MEASURES: The primary measure is
      the Team Check-up Tool (TCT), an original instrument that assesses context and
      progress of a team-based QI intervention. The TCT is administered monthly.
      Validation measures include CLABSI rate, Team Functioning Survey (TFS) and
      Practice Environment Scale (PES) from the Nursing Work Index. ANALYSIS: Temporal
      stability, responsiveness and validity of the TCT. RESULTS: We found evidence
      supporting the temporal stability, construct validity, and responsiveness of TCT
      measures of intervention activities, perceived group-level behaviors, and
      barriers to team progress. CONCLUSIONS: The TCT demonstrates good measurement
      reliability, validity, and responsiveness. By having more validated measures on
      implementation context, researchers can more readily conduct rigorous studies to
      identify contextual variables linked to key intervention and patient outcomes and
      strengthen the evidence base on successful spread of efficacious team-based
      interventions. QI teams participating in an intervention should also find data
      from a validated tool useful for identifying opportunities to improve their own
      implementation.

PMID- 21967863
TI  - Sampling epifauna, a necessity for a better assessment of benthic ecosystem
      functioning: an example of the epibenthic aggregated species Ophiothrix fragilis
      from the Bay of Seine.
AB  - Sampling the sea bottom surface remains difficult because of the surface
      hydraulic shock due to water flowing through the gear (i.e., the bow wave effect)
      and the loss of epifauna organisms due to the gear's closing mechanism. Slow
      moving mobile epifauna, such as the ophiuroid Ophiothrix fragilis, form high
      density patches in the English Channel, not only on pebbles like in the Dover
      Strait or offshore Brittany but also on gravel in the Bay of Seine (>5000 ind m(
      2)). Such populations form high biomasses and control the water transfer from the
      water column to the sediment. Estimating their real density and biomass is
      essential for the assessment of benthic ecosystem functioning using trophic web
      modelling. In this paper, we present and discuss the patch patterns and sampling
      efficiency of the different methods for collecting in the dense beds of O.
      fragilis in the Bay of Seine. The large Hamon grab (0.25 m(-2)) highly under
      estimated the ophiuroid density, while the Smith McIntyre appeared adequate among
      the tested sampling grabs. Nowadays, diving sampling, underwater photography and
      videos with remote operated vehicle appear to be the recommended alternatives to
      estimate the real density of such dense slow-moving mobile epifauna.

PMID- 21967864
TI  - The contribution of benthic macrofauna to the nutrient filter in coastal lagoons.
AB  - Human activities in coastal areas have increased the occurrence of eutrophication
      events, especially in vulnerable ecosystems such as coastal lagoons. Although we
      have a general knowledge of the consequences of eutrophication in these
      ecosystems, some efforts need to be made to understand biotic feedbacks that
      could modify the response of the environment to nutrient enrichment. The plant
      mediated 'coastal filter' is one of the main factors that determine lagoonal
      efficiency in processing excess nutrients. In this context, the present paper
      examined the relative contribution of benthic macrofauna to the 'coastal filter'
      of a Mediterranean lagoon. The analysis of macrofaunal assemblages in the Mar
      Menor lagoon led to a clear differentiation between shallow areas of net nutrient
      recycling and exportation and deeper areas of net retention. These differences
      enhance nutrient removal from the water column, thus increasing the ecosystem's
      resistance to eutrophication.

PMID- 21967865
TI  - Narrower grid structure of artificial reef enhances initial survival of in situ
      settled coral.
AB  - The initial factors that cause a decline in the survival of in situ settled
      corals remain poorly understood. In this study, we demonstrated through field
      experiments that the design of artificial grid plates may influence the initial
      survival of Acropora corals, with narrower grids being the most effective. In
      fact, grid plates with a 2.5-cm mesh presented the highest recorded survival rate
      (14%) at 6 months after settlement (representing approximately 50 corals per 0.25
      m(2) of plate). This is the first study where such high survival rates, matching
      those of cultures under aquarium conditions, were obtained in the field without
      using additional protective measures, such as guard nets against fish grazing
      after seeding. Therefore, our results provide a foundation for establishing new
      and effective coral restoration techniques for larval seeding, in parallel to
      clarifying the details of the early life stages of reef-building corals.

PMID- 21967866
TI  - Effect of rhTACI-Ig fusion protein on antigen-specific T cell responses from
      keyhole limpet haemocyanin challenged mice.
AB  - In addition to modulate B cells function, B cell activating factor belonged to
      TNF family (BAFF) also regulates T cells response via BAFFR and transmembrane
      activator and calcium modulator and cyclophilin-ligand interactor (TACI)
      expressing on activated T cells. This study explored the effect of a recombinant
      fusion protein containing the extracellular ligand-binding portion of TACI and
      the Fc portion of human immunoglobulin G (TACI-Ig) on activated T cells that were
      obtained from antigen-specific T-cell responses mice model induced by keyhole
      limpet haemocyanin (KLH), the characteristics of KLH-challenged mice were
      observed simultaneously. KLH immunization leaded to a significant positive
      relationship between BAFF level in serum and the extent of spleen histopathology.
      Serum concentration of BAFF, APRIL, IgM and IgG antibodies to KLH, and IL-4 were
      increased under KLH immunization, but IL-2 synthesis was decreased, resulting in
      a downregulation of IL-2/IL-4 ratio. Antigen-specific T cells proliferation, IL-5
      production, the percentage of Th and activation T cells were significantly
      upregulated, however, IL-2 secretion and the percentage of naive T cells were
      downregulated in vitro. RhBAFF co-stimulation further evoked T cells hyperplasy,
      IL-4 and IFN-gamma expression, the subgroups of Th, early antigen activation and
      activation T cells were also further increased. On the contrary, naive T cells
      were further reduced under rhBAFF stimuli. Administration of rhTACI-Ig
      significantly inhibited T cells proliferation, cytokines production and T cells
      differentiation, and the inhibitory effects might be associated with its ability
      to neutralize both the exogenous and endogenetic BAFF and APRIL.

PMID- 21967867
TI  - Genomic structure of grass carp Mx2 and the association of its polymorphisms with
      susceptibility/resistance to grass carp reovirus.
AB  - Mx (myxovirus-resistant) proteins are induced by interferon and inhibit viral
      replication in many vertebrates. In the present study, the organization of grass
      carp (Ctenopharyngodon idella) Mx2 (CiMx2) gene sequence was elucidated and its
      single nucleotide polymorphisms (SNPs) were investigated to explore their
      association with susceptibility/resistance to grass carp reovirus (GCRV). The
      CiMx2 genomic sequence is composed of 8108 bp, containing 12 exons and 11
      introns. Exon size ranges from 29 to 648 bp, and intron size varies from 89 to
      1925 bp. Five SNPs were discovered in the complete sequence of CiMx2 genomic
      sequence and four of them were found to be located in introns. The 7 C/T locus is
      a non-synonymous mutation. The genotype and allele distribution were examined by
      PCR-RFLP in susceptible and resistant fish. The results indicate that genotypes
      at the 1191 C/A and 1205 G/A loci are significantly associated with the
      resistance of grass carp to GCRV (P<0.05). To further verify the correlation, an
      additional infection experiment was carried out. The mortality in CC genotype
      individuals (0%) at 1191 C/A locus was significantly lower than that in AA
      (61.11%) and AC (71.17%) genotypes (P<0.05). At 1205 G/A site, no AA genotype
      individual was found; the mortality in AG genotype group was 53.06%, which was
      significantly lower than that in GG genotype group (90.48%) (P<0.05). The results
      demonstrate that genotype 1191 AC, 1191 AA and 1205 GG individuals are
      susceptible to GCRV, while 1191 CC and 1205 AG are resistant. The 7 C/T and 528
      C/T loci are in high linkage disequilibrium, however, no significant association
      was found between the haplotype and resistance to GCRV (P>0.05). These results
      provide potential markers for further investigation of selective breeding of
      resistant grass carp to GCRV.

PMID- 21967868
TI  - Involvement of the TREM-1/DAP12 pathway in the innate immune responses to
      Porphyromonas gingivalis.
AB  - Porphyromonas gingivalis, is a Gram-negative obligate oral anaerobic bacterium
      highly implicated in periodontal disease, the most prevalent chronic inflammatory
      disease, but recent evidence also indicates a potential contribution to systemic
      inflammation. The Triggering Receptor Expressed on Myeloid cells 1 (TREM-1) is a
      cell surface receptor of the immunoglobulin superfamily, which, along with its
      adaptor signalling molecule DAP12, is involved in immune response to bacterial
      and fungal infections, particularly by amplifying the production of pro
      inflammatory cytokines by the host. The aim of the present study was to
      investigate the effect of P. gingivalis on the expression of the TREM-1/DAP12
      pathway, as well as its engagement in pro-inflammatory cytokine production, by
      the myelomonocytic cell line MonoMac-6. P. gingivalis enhanced TREM-1 gene
      expression by the cells, concomitantly to an increase of soluble TREM-1
      secretion. Engagement of TREM-1, by introducing anti-TREM-1 to the experimental
      system, resulted in further potentiation of the pro-inflammatory responses to P.
      gingivalis, as evaluated by a further enhancement of interleukin (IL)-1beta and
      IL-6 secretion. On the contrary, the synthetic TREM-1 antagonist LP17 reduced the
      P. gingivalis-induced IL-1beta and IL-6 secretion by approximately 50%. In
      conclusion, the putative periodontal pathogen P. gingivalis can positively
      regulate the expression of the TREM-1/DAP12 pathway in monocytic cells. Moreover,
      engagement of TREM-1 can further potentiate the pro-inflammatory responses to P.
      gingivalis infection. This effect may contribute not only to the pathogenesis of
      inflammatory periodontal disease, but also to the enhancement of systemic
      inflammation.

PMID- 21967869
TI  - Muckle-Wells syndrome effectively treated with canakinumab: is the recommended
      dosing schedule mandatory?
AB  - Cryopyrin-associated periodic fever syndrome (CAPS) is a rare inherited disease
      due to mutations in the NLRP3 (also called CIAS1) gene on chromosome 1q44
      resulting in overproduction of interleukin-1. CAPS comprises three clinically
      overlapping disorders including Muckle-Wells syndrome. We report on two half
      siblings with Muckle-Wells syndrome who were successfully treated with the
      interleukin-1 beta antibody canakinumab. Despite reduced dosing and longer
      treatment intervals compared to the recommended dosing schedule (e.g. 150 mg
      every 8 weeks), the efficacy and tolerability of canakinumab was impressive in
      both patients. The pharmacologic properties of canakinumab are reviewed and the
      clinical and economical aspects highlighted. We show that with individualized
      'reflare-guided' administrations of canakinumab overall costs could
      hypothetically be reduced by 50% (approx. USD 60,000/patient/year) and therefore
      could have a major impact on treatment costs.

PMID- 21967870
TI  - Effects of selective H.E.L.P. LDL-apheresis on plasma inflammatory markers
      concentration in severe dyslipidemia: Implication for anti-inflammatory response.
AB  - Therapeutic plasmapheresis is a recognized medical procedure in which various
      techniques are used to separate and remove undesirable or excessively elevated
      plasma elements from blood. The main purpose of the procedure is to remove the
      substances responsible for the disease (autoantibodies, circulating immune
      complexes, lipoproteins and other molecules) from the patient's blood. Low
      Density-Lipoproteins-apheresis (LDL_a) is the selective removal of all
      apolipoprotein-B100-containing lipoproteins: LDL, very low-density lipoprotein,
      and lipoprotein (a). They are lowered acutely by 65-75%. There is little effect
      on other plasma lipidic and non-lipidic components. LDL_a was reported to
      increase resistance of LDL to oxidation, counteract procoagulatory state and
      relief disturbances of hemorheology associated with atherosclerosis. These
      effects are likely to be regarded as to be pleiotropic effects. In the sense that
      they are not necessarily related to the apolipoprotein-B100-containing
      lipoproteins level in plasma. There is robust evidence that LDL_a can induce the
      stabilization of atherosclerotic plaques through its lipid-lowering action.
      However, other effects unrelated to the apolipoprotein-B100-containing
      lipoproteins extracorporeal removal, such as the decrease of cytokines and
      adhesion molecules induced by LDL_a were also reported. Altogether these actions
      are thought to favorably influence regression of florid, nonfibrous
      atherosclerotic lesions through a blockade of lipid deposition in the vessel
      wall, plaque stabilization, and ultimately, coronary and extracoronary artery
      disease progression. This brief review provides some indication on existing
      evidence of Heparin-induced Extracorporeal Low-density-lipoprotein Precipitation
      LDL_a effects on plasma mediators of inflammation.

PMID- 21967872
TI  - [EDITORIAL. Changes in the practice of immunotherapy in Mexico: The new Clinical
      Practice Guidelines].

PMID- 21967871
TI  - Interferon production by cells infected with subacute sclerosing panencephalitis
      (SSPE) virus or measles virus.
AB  - BACKGROUND: Subacute sclerosing panencephalitis (SSPE) is a rare progressive
      neurodegenerative encephalitis caused by some variants of measles virus (MV). The
      structure of SSPE virus in the brains of SSPE patients is different from that of
      MV. The difference in interferon (IFN) production between cells infected with
      SSPE virus and those infected with MV remains unclear. METHODS: We measured the
      concentrations of IFN-alpha, beta, gamma, and lambda1 (interleukin (IL)-29) from
      MV- or SSPE virus-infected B95a cells (a marmoset B-lymphoblastoid cell line).
      RESULTS: SSPE virus-infected B95a cells produced significantly higher levels of
      IFN-alpha and lambda1 than did MV-infected or mock-infected cells. CONCLUSION:
      Our results suggest that SSPE virus and MV induce different IFN production
      profiles.

PMID- 21967873
TI  - [Mexican clinical practice guidelines of immunotherapy 2011].
AB  - BACKGROUND: Several international guidelines on immunotherapy exist, but they
      only apply partially in Mexico. The Mexican guideline of immunotherapy dates from
      1998. OBJECTIVES: To establish clinical recommendations and suggestions for
      Allergy residents and specialists for skin testing and allergen immunotherapy
      based on evidence and Mexican expert opinion, according to the GRADE system.
      METHODS: The guidelines were developed following the methodology of a guideline
      for clinical practice starting with the formulation of clinical questions, in the
      context of Mexican environmental conditions and morbidity, with the participation
      of allergists from all regions of the country. External validation was obtained.
      Its development followed three steps: 1. formulation of 24 clinical questions. 2.
      Search for consensus on the answers among members of the Regional chapters of
      both Mexican Colleges of Allergists (CMICA and COMPEDIA) during regional
      meetings. 3. Literature search for articles related to the questions and grading
      of its quality according to GRADE. RESULTS: Based on the regional consensus, 116
      articles and the safety, patient acceptance/ comfort and cost clinical
      recommendations and suggestions were developed on basic aspects of skin testing,
      subcutaneous and sublingual immunotherapy (patient preparation, vial preparation
      and application schedules) and the treatment of eventual adverse reactions.
      CONCLUSIONS: A clinical guideline was developed respecting particular
      methodology, validated by CMICA and COMPEDIA for its implementation among Mexican
      allergists. Several aspects deserve further study to improve scientific evidence.
      KEYWORDS: Allergen immunotherapy, subcutaneous immunotherapy, sublingual
      immunotherapy, skin testing, allergy diagnosis, rhinitis, asthma, atopic
      dermatitis, house dust mite, pollens, anaphylaxis, adrenaline, Mexico.

PMID- 21967874
TI  - Improving the prevention, diagnosis and treatment of TB among people living with
      HIV: the role of operational research.
AB  - Operational research is necessary to improve the access to and delivery of
      tuberculosis prevention, diagnosis and treatment interventions for people living
      with HIV. We conducted an extensive review of the literature and reports from
      recent expert consultations and research-related meetings organized by the World
      Health Organization and the Stop TB Partnership to identify a TB/HIV operational
      research agenda. We present critical operational research questions in a series
      of key areas: optimizing TB prevention by enhancing the uptake of isoniazid
      preventive therapy and the implementation of infection control measures;
      assessing the effectiveness of existing diagnostic tools and scaling up new
      technologies; improving service delivery models; and reducing risk factors for
      mortality among TB patients living with HIV. We discuss the potential impact that
      addressing the operational research questions may have on improving programmes'
      performance, assessing new strategies or interventions for TB control, or
      informing global or national policy formulation. Financial resources to implement
      these operational research questions should be mobilized from existing and new
      funding mechanisms. National TB and HIV/AIDS programmes should develop their
      operational research agendas based on these questions, and conduct the research
      that they consider crucial for improving TB and HIV control in their settings in
      collaboration with research stakeholders.

PMID- 21967875
TI  - Critical care medicine: art, science, and outcome.

PMID- 21967876
TI  - Different genospecies of Acinetobacter calcoaceticus-Acinetobacter baumannii
      complex associated with different outcomes.

PMID- 21967877
TI  - Multidrug-resistant Acinetobacter baumannii infection is not an independent risk
      factor for mortality in critically ill patients with hematologic malignancy.

PMID- 21967878
TI  - Characterization of temporal evolution of metabolic acidosis in adult patients
      with severe diabetic ketoacidosis admitted to the intensive care unit: not quite
      done.

PMID- 21967880
TI  - Tracheostomy scar and severe cough: more lessons.

PMID- 21967881
TI  - [Spanish implantable cardioverter-defibrillator registry. Seventh official report
      of the spanish society of cardiology working group on implantable cardioverter
      defibrillators (2010)].
AB  - INTRODUCTION AND OBJECTIVES: The authors summarize the findings of the Spanish
      Implantable Cardioverter-Defibrillator Registry for 2010 compiled by the Spanish
      Society of Cardiology Working Group on Implantable Cardioverter-Defibrillators.
      METHODS: Members of the Spanish Society of Cardiology were prospectively
      surveyed; data were recorded voluntarily by each implantation team on one-page
      questionnaires. RESULTS: In total, 4627 device implantations were reported,
      comprising 85.6% of the overall estimated number of implantations. The reported
      implantation rate was 100.61 per million population and the estimated total
      implantation rate was 117.50 per million. The proportion of first implantations
      was 73.87%. We collected data from 143 hospitals (9 more than in 2009). The
      majority of the implantable cardioverter-defibrillator implantations were
      performed in men (81%). The mean age was 62.5 +/- 13 years. Most of the patients
      had severe or moderate-to-severe ventricular dysfunction and were in New York
      Heart Association functional class II. Ischemic heart disease was the most
      frequent underlying cardiac condition, followed by dilated cardiomyopathy. The
      number of implantable cardioverter-defibrillator implantations indicated for
      primary prevention increased over the previous year and now accounts for 65.6% of
      first implantations. In all, 76.1% of the implantable cardioverter-defibrillator
      implantations were performed by cardiac electrophysiologists. CONCLUSIONS: The
      2010 Spanish Implantable Cardioverter-Defibrillator Registry includes data on
      almost 86% of all the implantable cardioverter-defibrillator implantations
      performed in Spain. Although the number has continued to increase, it still
      remains far lower than the European average. There has been a significant
      increase in the number of implantations indicated for primary prevention.

PMID- 21967882
TI  - Regulation of lipoprotein lipase gene expression by insulin and troglitazone in
      rainbow trout (Oncorhynchus mykiss) adipocyte cells in culture.
AB  - Adipose tissue plays a central role regulating the balance between deposition and
      mobilization of lipid reserves. Lipoprotein lipase (LPL) is a key enzyme
      controlling lipid accumulation in mammals and fish. In the present study, we have
      examined the expression of LPL in rainbow trout cultured adipocytes and we have
      investigated the effect of troglitazone, a member of thiazolidinediones (TZDs),
      and insulin on its expression. LPL gene expression increased from day 1 until day
      12 of culture, and the level was maintained up to day 21. The addition of insulin
      at 10 nM and 1.7 MUM increased significantly LPL gene expression in
      undifferentiated cells (days 7 to 12 maintained in growth medium). Nevertheless,
      treatment of day 7 cells incubated in growth medium with troglitazone (5 MUM) or
      troglitazone plus insulin (1 MUM each), tended to enhance LPL expression. In
      addition, LPL mRNA levels increased significantly in the presence of 1 MUM and 5
      MUM of troglitazone (days 7 to 12) when the cells were induced to differentiate
      by addition of differentiation medium. Although troglitazone alone (1 MUM) did
      not stimulate lipid accumulation in the cells neither in growth nor in
      differentiation medium, the simultaneous presence of troglitazone (1 MUM) and
      insulin (1 MUM) increased significantly the content of triglycerides in adipocyte
      cells maintained in growth medium (days 7 to 12). These results indicate that
      insulin and troglitazone regulate LPL gene expression during adipocyte
      differentiation and suggest that both factors may have combined effects in the
      modulation of adipogenesis.

PMID- 21967883
TI  - Photosystem II.

PMID- 21967884
TI  - Nitration of tyrosines 46 and 48 induces the specific degradation of cytochrome c
      upon change of the heme iron state to high-spin.
AB  - The Reactive Nitrogen and Oxygen Species (the so-called RNOS), which are well
      known radicals formed in the mitochondria under nitro-oxidative cell stress, are
      responsible for nitration of tyrosines in a wide variety of proteins and, in
      particular, in cytochrome c (Cc). Only three out of the five tyrosine residues of
      human Cc, namely those at positions 67, 74 and 97, have been detected in vivo as
      nitrotyrosines. However, nitration of the two other tyrosines, namely those at
      positions 46 and 48, has never been detected in vivo despite they are both well
      exposed to solvent. Here we investigate the changes in heme coordination and
      alkaline transition, along with the peroxidase activity and in cell degradation
      of Cc mutants in which all their tyrosine residues - with the only exception of
      that at position 46 or 48 - are replaced by phenylalanines. In Jurkat cell
      extracts devoid of proteases inhibitors, only the high-spin iron nitrated forms
      of these monotyrosine mutants are degraded. Altogether the resulting data suggest
      that nitration of tyrosines 46 and 48 makes Cc easily degradable upon turning the
      heme iron state to high-spin.

PMID- 21967886
TI  - Minocycline produced antidepressant-like effects on the learned helplessness rats
      with alterations in levels of monoamine in the amygdala and no changes in BDNF
      levels in the hippocampus at baseline.
AB  - Previous studies have indicated that minocycline might function as an
      antidepressant drug. The aim of this study was to evaluate the antidepressant
      like effects of minocycline, which is known to suppress activated microglia,
      using learned helplessness (LH) rats (an animal model of depression). Infusion of
      minocycline into the cerebral ventricle of LH rats induced antidepressant-like
      effects. However, infusion of minocycline into the cerebral ventricle of naive
      rats did not produce locomotor activation in the open field tests, suggesting
      that the antidepressant-like effects of minocycline were not attributed to the
      enhanced locomotion. LH rats showed significantly higher serotonin turnover in
      the orbitofrontal cortex and lower levels of brain-derived neurotrophic factor
      (BDNF) in the hippocampus than control rats. However, these alterations in
      serotonin turnover and BDNF expression remained unchanged after treatment with
      minocycline. On the contrary, minocycline treatment of LH rats induced
      significant increases in the levels of dopamine and its metabolites in the
      amygdala when compared with untreated LH rats. Taken together, minocycline may be
      a therapeutic drug for the treatment of depression.

PMID- 21967885
TI  - A role for 5-HT1A receptors in the basolateral amygdala in the development of
      conditioned defeat in Syrian hamsters.
AB  - The basolateral nucleus of the amygdala (BLA) is a key brain region regulating
      behavioral changes following stressful events, including social defeat. Previous
      research has shown that activation of serotonin (5-HT) 1A receptors in the BLA
      reduces conditioned fear and anxiety-like behavior. The objective of this study
      was to test whether 5-HT1A receptors in the BLA contribute to conditioned defeat
      in male Syrian hamsters (Mesocricetus auratus). We tested whether injection of
      the selective 5-HT1A receptor agonist flesinoxan (400 ng, 800 ng, or 1200 ng in
      200 nl saline) into the BLA prior to social defeat would reduce the acquisition
      of conditioned defeat, and whether a similar injection prior to testing would
      reduce the expression of conditioned defeat. We also tested whether injection of
      the selective 5-HT1A receptor antagonist WAY-100635 (400 ng or 1600 ng in 200 nl
      saline) into the BLA prior to social defeat would enhance the acquisition of
      conditioned defeat, and whether a similar injection prior to testing would
      enhance the expression of conditioned defeat. We found that injection of
      flesinoxan into the BLA decreased both the acquisition and expression of
      conditioned defeat. However, injection of WAY-100635 into the BLA did not alter
      the acquisition or expression of conditioned defeat. These data indicate that
      pharmacological activation of 5-HT1A receptors in the BLA is sufficient to impair
      the acquisition and expression of conditioned defeat. Our results suggest that
      pharmacological treatments that activate 5-HT1A receptors in the BLA are capable
      of reducing the development of stress-induced changes in behavior.

PMID- 21967888
TI  - Mirage effect from thermally modulated transparent carbon nanotube sheets.
AB  - The single-beam mirage effect, also known as photothermal deflection, is studied
      using a free-standing, highly aligned carbon nanotube aerogel sheet as the heat
      source. The extremely low thermal capacitance and high heat transfer ability of
      these transparent forest-drawn carbon nanotube sheets enables high frequency
      modulation of sheet temperature over an enormous temperature range, thereby
      providing a sharp, rapidly changing gradient of refractive index in the
      surrounding liquid or gas. The advantages of temperature modulation using carbon
      nanotube sheets are multiple: in inert gases the temperature can reach > 2500 K;
      the obtained frequency range for photothermal modulation is ~100 kHz in gases and
      over 100 Hz in high refractive index liquids; and the heat source is transparent
      for optical and acoustical waves. Unlike for conventional heat sources for
      photothermal deflection, the intensity and phase of the thermally modulated beam
      component linearly depends upon the beam-to-sheet separation over a wide range of
      distances. This aspect enables convenient measurements of accurate values for
      thermal diffusivity and the temperature dependence of refractive index for both
      liquids and gases. The remarkable performance of nanotube sheets suggests
      possible applications as photo-deflectors and for switchable invisibility cloaks,
      and provides useful insights into their use as thermoacoustic projectors and
      sonar. Visibility cloaking is demonstrated in a liquid.

PMID- 21967889
TI  - Carotid stent fracture and restenosis management.
AB  - We report an unusual case of asymptomatic accelerated right carotid artery in
      stent restenosis in a patient referred for revascularization of a de novo
      stenosis of her left internal carotid artery.

PMID- 21967887
TI  - Validity of instruments to measure physical activity may be questionable due to a
      lack of conceptual frameworks: a systematic review.
AB  - BACKGROUND: Guidance documents for the development and validation of patient
      reported outcomes (PROs) advise the use of conceptual frameworks, which outline
      the structure of the concept that a PRO aims to measure. It is unknown whether
      currently available PROs are based on conceptual frameworks. This study, which
      was limited to a specific case, had the following aims: (i) to identify
      conceptual frameworks of physical activity in chronic respiratory patients or
      similar populations (chronic heart disease patients or the elderly) and (ii) to
      assess whether the development and validation of PROs to measure physical
      activity in these populations were based on a conceptual framework of physical
      activity. METHODS: Two systematic reviews were conducted through searches of the
      Medline, Embase, PsycINFO, and Cinahl databases prior to January 2010. RESULTS:
      In the first review, only 2 out of 581 references pertaining to physical activity
      in the defined populations provided a conceptual framework of physical activity
      in COPD patients. In the second review, out of 103 studies developing PROs to
      measure physical activity or related constructs, none were based on a conceptual
      framework of physical activity. CONCLUSIONS: These findings raise concerns about
      how the large body of evidence from studies that use physical activity PRO
      instruments should be evaluated by health care providers, guideline developers,
      and regulatory agencies.

PMID- 21967890
TI  - Do patients with bipolar disorder drink alcohol for different reasons when
      depressed, manic or euthymic?
AB  - OBJECTIVE: Many studies report high prevalence rates for co-morbid alcohol
      problems in bipolar disorder (BP). Some hypothesize that individuals use alcohol
      to self-medicate, but few studies examine the range of possible reasons and none
      explicitly explores the role of mood state. We examined drinking motives in BP
      depression, (hypo)mania and euthymia according to Cooper's cognitive motivational
      model of alcohol use (Cooper, 1994). METHODS: Twenty-seven participants with BP
      were interviewed using the Drinking Motives Questionnaire. A calendar-based
      measure of alcohol use--the FORM90--was used to aid recall of drink-related
      behaviours and estimate alcohol intake. Each participant reported drinking
      motives and alcohol consumption for 30 consecutive days of euthymia, plus one
      past depressive and one past (hypo)manic episode. RESULTS: Estimated alcohol
      intake was higher when depressed or (hypo)manic compared with euthymia. Drinking
      motives varied between mood states. Negative internal coping motives were
      specifically related to depression, whilst positive internal and external motives
      were more specifically related to (hypo)mania. During euthymia, the patients'
      motives did not differ from norms. CONCLUSIONS: This is the first clinical study
      utilising a clearly defined cognitive motivational model demonstrating that the
      reasons to drink alcohol in patients with BP are mood-dependent. Interventions
      aimed at modifying problematic drinking behaviours in this population must take
      into account both individual and mood state variations in reasons for alcohol
      consumption. Self-medication or inadequate coping is not sufficient to generally
      explain alcohol intake across mood states and individuals.

PMID- 21967891
TI  - Increased IgA responses to the LPS of commensal bacteria is associated with
      inflammation and activation of cell-mediated immunity in chronic fatigue
      syndrome.
AB  - BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is
      accompanied by a) systemic IgA/IgM responses against the lipopolysaccharides
      (LPS) of commensal bacteria; b) inflammation, e.g. increased plasma interleukin
      (IL)1 and tumor necrosis factor (TNF)alpha; and c) activation of cell-mediated
      immunity (CMI), as demonstrated by increased neopterin. METHODS: To study the
      relationships between the IgA/IgM responses to the LPS of microbiota,
      inflammation, CMI and the symptoms of ME/CFS we measured the IgA/IgM responses to
      the LPS of 6 different enterobacteria, serum IL-1, TNFalpha, neopterin, and
      elastase in 128 patients with ME/CFS and chronic fatigue (CF). Severity of
      symptoms was assessed by the Fibromyalgia and Chronic Fatigue Syndrome (FF)
      Rating Scale. RESULTS: Serum IL-1, TNFalpha, neopterin and elastase are
      significantly higher in patients with ME/CFS than in CF patients. There are
      significant and positive associations between the IgA responses to LPS and serum
      IL-1, TNFalpha, neopterin and elastase. Patients with an abnormally high IgA
      response show increased serum IL-1, TNFalpha and neopterin levels, and higher
      ratings on irritable bowel syndrome (IBS) than subjects with a normal IgA
      response. Serum IL-1, TNFalpha and neopterin are significantly related to
      fatigue, a flu-like malaise, autonomic symptoms, neurocognitive disorders,
      sadness and irritability. CONCLUSIONS: The findings show that increased IgA
      responses to commensal bacteria in ME/CFS are associated with inflammation and
      CMI activation, which are associated with symptom severity. It is concluded that
      increased translocation of commensal bacteria may be responsible for the disease
      activity in some ME/CFS patients.

PMID- 21967892
TI  - Prognostic factors of atrial fibrillation following elective coronary artery
      bypass grafting: the impact of quantified intraoperative myocardial ischemia.
AB  - BACKGROUND: Atrial fibrillation (AF) occurs in 28-33% of the patients undergoing
      coronary artery revascularization (CABG). This study focuses on both pre- and
      peri-operative factors that may affect the occurrence of AF. The aim is to
      identify those patients at higher risk to develop AF after CABG. PATIENTS AND
      METHODS: Two patient cohorts undergoing CABG were retrospectively studied. The
      first group (group A) consisted of 157 patients presenting AF after elective
      CABG. The second group (group B) consisted of 191 patients without AF
      postoperatively. RESULTS: Preoperative factors presenting significant correlation
      with the incidence of post-operative AF included: 1) age > 65 years (p = 0.029),
      2) history of AF (p = 0.022), 3) chronic obstructive pulmonary disease (p =
      0.008), 4) left ventricular dysfunction with ejection fraction < 40% (p = 0.015)
      and 5) proximal lesion of the right coronary artery (p = 0.023). The
      intraoperative factors that appeared to have significant correlation with the
      occurrence of postoperative AF were: 1) CPB-time > 120 minutes (p = 0.011), 2)
      myocardial ischemia index < 0.27 ml.m2/Kg.min (p = 0.011), 3) total positive
      fluid-balance during ICU-stay (p < 0.001), 4) FiO2/PO2 > 0, 4 after extubation
      and during the ICU-stay (p = 0.021), 5) inotropic support with doses 15-30
      MUg/Kg/min (p = 0.016), 6) long ICU-stay recovery for any reason (p < 0.001) and
      perioperative myocardial infarction (p < 0.001). CONCLUSIONS: Our results suggest
      that the incidence of post-CABG atrial fibrillation can be predicted by specific
      preoperative and intraoperative measures. The intraoperative myocardial ischemia
      can be sufficiently quantified by the myocardial ischemia index. For those
      patients at risk we would suggest an early postoperative precautionary anti
      arrhythmic treatment.

PMID- 21967893
TI  - Complement-fixing anti-type VII collagen antibodies are induced in Th1-polarized
      lymph nodes of epidermolysis bullosa acquisita-susceptible mice.
AB  - The environment encountered in secondary lymphoid organs (e.g., lymph nodes)
      influences the outcome of immune responses. Immunization of mice with type VII
      collagen, an adhesion protein expressed at the cutaneous basement membrane,
      induces experimental epidermolysis bullosa acquisita (EBA). In this model,
      clinical disease is associated with the H2s haplotype of the MHC found in SJL/J
      mice. Most other strains (e.g., BALB/c, C57BL/6, NZM2410/J) are resistant to
      clinical disease, despite autoantibody production. Comparison of autoantibody
      response in EBA-resistant and -susceptible mice showed an IgG2-dominated response
      in the latter. We hypothesized that EBA susceptibility is due to specific
      cytokine gene expression in draining lymph nodes (dLN). To challenge this
      hypothesis, EBA-susceptible (SJL/J) and -resistant (BALB/c, C57BL/6) mice were
      immunized with type VII collagen, followed by analysis of clinical phenotype,
      subclasses of circulating and tissue-bound autoantibodies, complement activation,
      and cytokine gene expression in dLN. Disease manifestation was associated with
      induction of complement-fixing autoantibodies, confirming previous observations.
      Furthermore, however, IFN-gamma/IL-4 ratio in dLN of EBA-susceptible mice was
      significantly increased compared with EBA-resistant strains, suggesting a Th1
      polarization. Immunization of H2s-congenic C57BL/6 mice (B6.SJL-H2s) led to Th1
      polarization in dLN and clinical disease. In addition to their cytokine milieu,
      EBA-susceptible and -resistant mice also differed regarding the expression of
      FcgammaR on peripheral leukocytes, in which a higher FcgammaRIV expression in
      SJL/J and B6.SJL-H2s mice, compared with C57BL/6, was associated with skin
      lesions. In summary, blistering in experimental EBA is regulated by both adaptive
      (divergent class switch recombination due to polarized cytokine expression) and
      innate (FcgammaR expression) immune mechanisms.

PMID- 21967894
TI  - IL-15-high-responder developing NK cells bearing Ly49 receptors in IL-15-/- mice.
AB  - In mice lacking IL-15, NK cell development is arrested at immature stages,
      providing an opportunity to investigate the earliest developing NK cells that
      would respond to IL-15. We show in this study that immature NK cells were present
      in the spleen as well as bone marrow (BM) and contained IL-15-high-responder
      cells. Thus, mature NK cells were generated more efficiently from IL-15(-/-) than
      from control donor cells in radiation BM chimeras, and the rate of IL-15-induced
      cell division in vitro was higher in NK cells in the spleen and BM from IL-15(-/
      ) mice than in those from wild-type mice. Phenotypically, NK cells developed in
      IL-15(-/-) mice up to the minor but discrete CD11b(
      )CD27(+)DX5(hi)CD51(dull)CD127(dull)CD122(hi) stage, which contained the majority
      of Ly49G2(+) and D(+) NK cells both in the spleen and BM. Even among wild-type
      splenic NK cells, IL-15-induced proliferation was most prominent in CD11b(
      )DX5(hi) cells. Notably, IL-15-mediated preferential expansion (but not
      conversion from Ly49(-) cells) of Ly49(+) NK cells was observed in vitro only for
      NK cells in the spleen. These observations indicated the uneven distribution of
      NK cells of different developing stages with variable IL-15 responsiveness in
      these lymphoid organs. Immature NK cells in the spleen may contribute, as
      auxiliaries to those in BM, to the mature NK cell compartment through IL-15
      driven extramarrow expansion under steady-state or inflammatory conditions.

PMID- 21967895
TI  - Segregated regulatory CD39+CD4+ T cell function: TGF-beta-producing Foxp3- and IL
      10-producing Foxp3+ cells are interdependent for protection against collagen
      induced arthritis.
AB  - Oral immunization with a Salmonella vaccine vector expressing enterotoxigenic
      Escherichia coli colonization factor Ag I (CFA/I) can protect against collagen
      induced arthritis (CIA) by dampening IL-17 and IFN-gamma via enhanced IL-4, IL
      10, and TGF-beta. To identify the responsible regulatory CD4(+) T cells making
      the host refractory to CIA, Salmonella-CFA/I induced CD39(+)CD4(+) T cells with
      enhanced apyrase activity relative to Salmonella vector-immunized mice. Adoptive
      transfer of vaccine-induced CD39(+)CD4(+) T cells into CIA mice conferred
      complete protection, whereas CD39(-)CD4(+) T cells did not. Subsequent analysis
      of vaccinated Foxp3-GFP mice revealed the CD39(+) T cells were composed of Foxp3
      GFP(-) and Foxp3-GFP(+) subpopulations. Although each adoptively transferred
      Salmonella-CFA/I-induced Foxp3(-) and Foxp3(+)CD39(+)CD4(+) T cells could protect
      against CIA, each subset was not as efficacious as total CD39(+)CD4(+) T cells,
      suggesting their interdependence for optimal protection. Cytokine analysis
      revealed Foxp3(-) CD39(+)CD4(+) T cells produced TGF-beta, and
      Foxp3(+)CD39(+)CD4(+) T cells produced IL-10, showing a segregation of function.
      Moreover, donor Foxp3-GFP(-) CD4(+) T cells converted to Foxp3-GFP(+)
      CD39(+)CD4(+) T cells in the recipients, showing plasticity of these regulatory T
      cells. TGF-beta was found to be essential for protection because in vivo TGF-beta
      neutralization reversed activation of CREB and reduced the development of
      CD39(+)CD4(+) T cells. Thus, CD39 apyrase-expressing CD4(+) T cells stimulated by
      Salmonella-CFA/I are composed of TGF-beta-producing Foxp3(-) CD39(+)CD4(+) T
      cells and support the stimulation of IL-10-producing Foxp3(+) CD39(+)CD4(+) T
      cells.

PMID- 21967896
TI  - A mimic of viral double-stranded RNA triggers fulminant type 1 diabetes-like
      syndrome in regulatory T cell-deficient autoimmune diabetic mouse.
AB  - Human fulminant type 1 diabetes (FT1D) is an extremely aggressive disease. The
      delay of proper diagnosis results in high mortality. However, the pathophysiology
      of this disease remains unclear. We took advantage of CD28-deficient NOD (CD28(-/
      ) NOD) mice, which have limited numbers of regulatory T cells and develop
      aggressive autoimmune diabetes, to create a FT1D model that mimicked the disease
      in humans. Young CD28(-/-) NOD mice were injected with polyinosinic-polycytidylic
      acid to activate innate immunity in an effort to induce diabetes onset. In this
      model, innate immune cell activation precedes the onset of diabetes similar to
      ~70% of FT1D patients. Eighty-three percent of CD28(-/-) NOD mice developed
      diabetes within 1-6 d after injection of polyinosinic-polycytidylic acid.
      Moreover, T cells infiltrated the pancreatic exocrine tissue and destroyed alpha
      cells, an observation characteristic of human FT1D. We conclude that an FT1D-like
      phenotype can be induced in the background of autoimmune diabetes by a mimic of
      viral dsRNA, and this model is useful for understanding human FT1D.

PMID- 21967897
TI  - Cyclooxygenase-2 deficiency leads to intestinal barrier dysfunction and increased
      mortality during polymicrobial sepsis.
AB  - Sepsis remains the leading cause of death in critically ill patients, despite
      modern advances in critical care. Intestinal barrier dysfunction may lead to
      secondary bacterial translocation and the development of the multiple organ
      dysfunction syndrome during sepsis. Cyclooxygenase (COX)-2 is highly upregulated
      in the intestine during sepsis, and we hypothesized that it may be critical in
      the maintenance of intestinal epithelial barrier function during peritonitis
      induced polymicrobial sepsis. COX-2(-/-) and COX-2(+/+) BALB/c mice underwent
      cecal ligation and puncture (CLP) or sham surgery. Mice chimeric for COX-2 were
      derived by bone marrow transplantation and underwent CLP. C2BBe1 cells, an
      intestinal epithelial cell line, were treated with the COX-2 inhibitor NS-398,
      PGD(2), or vehicle and stimulated with cytokines. COX-2(-/-) mice developed
      exaggerated bacteremia and increased mortality compared with COX-2(+/+) mice
      following CLP. Mice chimeric for COX-2 exhibited the recipient phenotype,
      suggesting that epithelial COX-2 expression in the ileum attenuates bacteremia
      following CLP. Absence of COX-2 significantly increased epithelial permeability
      of the ileum and reduced expression of the tight junction proteins zonula
      occludens-1, occludin, and claudin-1 in the ileum following CLP. Furthermore,
      PGD(2) attenuated cytokine-induced hyperpermeability and zonula occludens-1
      downregulation in NS-398-treated C2BBe1 cells. Our findings reveal that absence
      of COX-2 is associated with enhanced intestinal epithelial permeability and leads
      to exaggerated bacterial translocation and increased mortality during peritonitis
      induced sepsis. Taken together, our results suggest that epithelial expression of
      COX-2 in the ileum is a critical modulator of tight junction protein expression
      and intestinal barrier function during sepsis.

PMID- 21967898
TI  - Early postmyocardial infarction survival in Murphy Roths Large mice is mediated
      by attenuated apoptosis and inflammation but depends on genetic background.
AB  - The Murphy Roths Large (MRL) mouse, a strain capable of regenerating right
      ventricular myocardium, has a high postmyocardial infarction (post-MI) survival
      rate compared with C57BL/6J (C57) mice. The biological processes responsible for
      this survival advantage are unknown. To assess the effect of genetic background,
      the LG/J strain, which harbours 75% of the MRL composite genome, was included in
      the study. The MRL survival advantage versus C57 mice (92 versus 68%, P < 0.05)
      occurred primarily in the first 5 days; LG/J survival was intermediate (P =
      n.s.). Microarray data analysis revealed an attenuation of apoptotic (P < 0.05)
      and stress response transcripts in MRL hearts compared with C57 hearts post-MI.
      Supporting the microarray results, there were fewer TUNEL-positive cells 1 day
      post-MI in MRL infarcts compared with C57 infarcts (P = 0.001) and fewer CD45
      positive cells in the MRL infarct border zone 2 days post-MI (P < 0.01); the LG/J
      results were intermediate (P = n.s.). The MRL hearts had smaller infarct scars
      and attenuated ventricular dilatation 30 days post-MI compared with C57 hearts (P
      < 0.05). We conclude that the early post-MI survival advantage of MRL mice over
      the C57 strain is mediated at least in part by reductions in apoptosis and
      inflammatory infiltration, and that these reductions may influence chronic
      remodelling. The intermediate survival, apoptosis and inflammation profile of
      LG/J mice suggests that this high tolerance for MI in the MRL mouse could be
      derived from its shared genetic background with the LG/J mouse.

PMID- 21967899
TI  - Rapid elimination of CO through the lungs: coming full circle 100 years on.
AB  - At the start of the 20th century, CO poisoning was treated by administering a
      combination of CO(2) and O(2) (carbogen) to stimulate ventilation. This treatment
      was reported to be highly effective, even reversing the deep coma of severe CO
      poisoning before patients arrived at the hospital. The efficacy of carbogen in
      treating CO poisoning was initially attributed to the absorption of CO(2);
      however, it was eventually realized that the increase in pulmonary ventilation
      was the predominant factor accelerating clearance of CO from the blood. The
      inhaled CO(2) in the carbogen stimulated ventilation but prevented hypocapnia and
      the resulting reductions in cerebral blood flow. By then, however, carbogen
      treatment for CO poisoning had been abandoned in favour of hyperbaric O(2). Now,
      a half-century later, there is accumulating evidence that hyperbaric O(2) is not
      efficacious, most probably because of delays in initiating treatment. We now also
      know that increases in pulmonary ventilation with O(2)-enriched gas can clear CO
      from the blood as fast, or very nearly as fast, as hyperbaric O(2). Compared with
      hyperbaric O(2), the technology for accelerating pulmonary clearance of CO with
      hyperoxic gas is not only portable and inexpensive, but also may be far more
      effective because treatment can be initiated sooner. In addition, the technology
      can be distributed more widely, especially in developing countries where the
      prevalence of CO poisoning is highest. Finally, early pulmonary CO clearance does
      not delay or preclude any other treatment, including subsequent treatment with
      hyperbaric O(2).

PMID- 21967901
TI  - Myocardial contractile and metabolic properties of familial hypertrophic
      cardiomyopathy caused by cardiac troponin I gene mutations: a simulation study.
AB  - Familial hypertrophic cardiomyopathy (FHC) is an inherited disease that is caused
      by sarcomeric protein gene mutations. The mechanism by which these mutant
      proteins cause disease is uncertain. Experimentally, cardiac troponin I (CTnI)
      gene mutations mainly alter myocardial performance via increases in the Ca(2+)
      sensitivity of cardiac contractility. In this study, we used an integrated
      simulation that links electrophysiology, contractile activity and energy
      metabolism of the myocardium to investigate alterations in myocardial contractile
      function and energy metabolism regulation as a result of increased Ca(2+)
      sensitivity in CTnI mutations. Simulation results reproduced the following
      typical features of FHC: (1) slower relaxation (diastolic dysfunction) caused by
      prolonged [Ca(2+)](i) and force transients; (2) higher energy consumption with
      the increase in Ca(2+) sensitivity; and (3) reduced fatty acid oxidation and
      enhanced glucose utilization in hypertrophied heart metabolism. Furthermore, the
      simulation indicated that in conditions of high energy consumption (that is, more
      than an 18.3% increase in total energy consumption), the myocardial energetic
      metabolic network switched from a net consumer to a net producer of lactate,
      resulting in a low coupling of glucose oxidation to glycolysis, which is a common
      feature of hypertrophied hearts. This study provides a novel systematic
      myocardial contractile and metabolic analysis to help elucidate the pathogenesis
      of FHC and suggests that the alterations in resting heart energy supply and
      demand could contribute to disease progression.

PMID- 21967900
TI  - The role of the subfornical organ in angiotensin II-salt hypertension in the rat.
AB  - Hypertension caused by chronic infusion of angiotensin II (Ang II) in
      experimental animals is dependent, in part, on increased activity of the
      sympathetic nervous system. This chronic sympathoexcitatory response is amplified
      by a high-salt diet, suggesting an interaction of circulating Ang II and dietary
      salt on sympathetic regulatory pathways in the brain. The present study tested
      the hypothesis that the subfornical organ (SFO), a forebrain circumventricular
      organ known to be activated by circulating Ang II, is crucial to the pathogenesis
      of hypertension induced by chronic Ang II administration in rats on a high-salt
      diet (Ang II-salt model). Rats were randomly selected to undergo either
      subfornical organ lesion (SFOx) or sham surgery (Sham) and then placed on a high
      salt (2% NaCl) diet. One week later, rats were instrumented for radiotelemetric
      measurement of mean arterial pressure (MAP) and heart rate (HR) and placed in
      metabolic cages to measure sodium and water balance. Baseline MAP was slightly
      (but not statistically) lower in SFOx compared with Sham rats during the 5 day
      control period. During the subsequent 10 days of Ang II administration, MAP was
      statistically lower in SFOx rats. However, when MAP responses to Ang II were
      analysed by comparing the change from the 5 day baseline period, only on the
      fifth day of Ang II was MAP significantly different between groups. There were no
      differences between groups for water or sodium balance throughout the protocol.
      We conclude that, although the SFO is required for the complete expression of Ang
      II-salt hypertension in the rat, other brain sites are also involved.

PMID- 21967902
TI  - Genomic predictors of trainability.
AB  - The concept of individual differences in the response to exercise training or
      trainability was defined three decades ago. In a series of experimental studies
      with pairs of monozygotic twins, evidence was found in support of a strong
      genotype dependency of the ability to respond to regular exercise. In the
      HERITAGE Family Study, it was observed that the heritability of the maximal
      oxygen uptake response to 20 weeks of standardized exercise training reached 47%
      after adjustment for age, sex, baseline maximal oxygen uptake and baseline body
      mass and composition. Candidate gene studies have not yielded as many validated
      gene targets and variants as originally anticipated. Genome-wide explorations
      have generated more convincing predictors of maximal oxygen uptake trainability.
      A genomic predictor score based on the number of favourable alleles carried at 21
      single nucleotide polymorphisms appears to be able to identify low and high
      training response classes that differ by at least threefold. Combining
      transcriptomic and genomic technologies has also yielded highly promising results
      concerning the ability to predict trainability among sedentary people.

PMID- 21967903
TI  - Moderate cardiac-selective overexpression of angiotensin II type 2 receptor
      protects cardiac functions from ischaemic injury.
AB  - We hypothesized that moderate cardiac-selective overexpression of the angiotensin
      II type 2 receptor (AT2R) would protect the myocardium from ischaemic injury
      after a myocardial infarction (MI) induced by coronary artery ligation. For in
      vitro studies, adenoviral vector expressing genomic DNA of AT2R and enhanced
      green fluorescence protein (EGFP) was used to overexpress AT2R in rat neonatal
      cardiac myocytes. Expression of AT2R, measured by real-time PCR and
      immunostaining, demonstrated efficient transduction of AT2R in a dose-dependent
      pattern. The AT2R constitutively induced apoptosis in rat neonatal cardiac
      myocytes in dose-dependent patterns. For in vivo studies, 4 * 10(10) vector
      genomes (vg) of recombinant adeno-associated virus serotype 9 (rAAV9)-chicken
      beta actin promoter-AT2R was injected into the left ventricle of 5-day-old
      Sprague-Dawley rats. At 6 weeks of age, hearts were harvested and expression of
      AT2R determined by real-time PCR and Western blotting. Expression was increased
      onefold over control hearts, and no apoptosis was detected. Two subsequent in
      vivo studies were performed. In a prevention study, 4 * 10(10) vg of rAAV9-CBA
      AT2R was injected into the left ventricle of 5-day-old Sprague-Dawley rats and MI
      was induced at 6 weeks of age. For a post-treatment study, 4 * 10(10) vg of rAAV9
      CBA-AT2R was administrated to the peri-infarcted myocardium area immediately
      after MI in 6-week-old animals. For both in vivo studies, cardiac functions were
      assessed using echocardiography and haemodynamic measurements 4 weeks after
      coronary artery ligation. In the in vivo studies, the rats subjected to MI showed
      significant decreases in fractional shortening and rate of change of left
      ventricular pressure, with increased left ventricular end-diastolic pressure and
      ventricular hypertrophy. For the prevention study, the moderate cardiac-selective
      overexpression of AT2R attenuated these MI-induced impairments and also caused a
      decrease in ventricular wall thinning. In the post-treatment study, the
      overexpression of AT2R partly reversed the MI-induced cardiac dysfunction.
      Myocardial infarction also induced the upregulation of angiotensin II type 1
      receptor, angiotensin-converting enzyme and collagen I mRNA expression, all of
      which were attenuated by the overexpression of AT2R. It is concluded that
      moderate cardiac-selective overexpression of AT2R protects heart function from
      ischaemic injury, which may be mediated, at least in part, through modulation of
      components of the cardiac renin-angiotensin system and collagen levels in the
      myocardium.

PMID- 21967904
TI  - Chitosan-based ultrathin films as antifouling, anticoagulant and antibacterial
      protective coatings.
AB  - Ultrathin antifouling and antibacterial protective nanocoatings were prepared
      from ionic derivatives of chitosan using layer-by-layer deposition methodology.
      The surfaces of silicon, and glass protected by these nanocoatings were resistant
      to non-specific adsorption of proteins disregarding their net charges at
      physiological conditions (positively charged TGF-beta1 growth factor and
      negatively charged bovine serum albumin) as well as human plasma components. The
      coatings also preserved surfaces from the formation of bacterial (Staphylococcus
      aureus) biofilm as shown using microscopic studies (SEM, AFM) and the MTT
      viability test. Moreover, the chitosan-based films adsorbed onto glass surface
      demonstrated the anticoagulant activity towards the human blood. The antifouling
      and antibacterial actions of the coatings were correlated with their
      physicochemical properties. The studied biologically relevant properties were
      also found to be dependent on the thickness of those nanocoatings. These
      materials are promising for biomedical applications, e.g., as protective coatings
      for medical devices, anticoagulant coatings and protective layers in membranes. 

PMID- 21967905
TI  - Influencing safe perioperative practice through leadership.

PMID- 21967906
TI  - Reaping what we sow: the costs of bullying.

PMID- 21967907
TI  - Preventing perioperative complications in the patient with a high body mass
      index.
AB  - Patients with a high body mass index (BMI) are being seen more frequently in
      perioperative settings, and staff members must be prepared to prevent
      complications (eg, difficult intubation, respiratory insufficiency, positioning
      injuries) that occur in this patient population as a result of comorbidities.
      After two sentinel events occurred during a six-month period at a community
      hospital in northern California, a task force was created to examine issues
      related to the care of patients who are morbidly obese and to develop and
      implement policies and procedures to reduce the risk of adverse patient outcomes.
      Chart audit results confirm that the quality improvement project was successful;
      92% of 50 charts showed inclusion of the BMI on the surgery schedule, and 94%
      showed inclusion of the BMI on the preoperative checklist. No positioning
      incidents or intubation emergencies have occurred in patients with a high BMI
      since January 1, 2009.

PMID- 21967908
TI  - Transitioning the older adult in the ambulatory care setting.
AB  - Transitions between care settings are periods of vulnerability for patients. This
      is especially true for older adults, for whom comorbidities and functional
      impairments can increase the complexity of care and the need for multiple
      caregivers can compromise safety. Poor care transitions can result in costly
      hospital admissions. For this reason, leading health care organizations have
      initiated programs to improve the quality of transitions; however, to date, the
      ambulatory surgical setting has not been a focus of these initiatives. The
      ambulatory setting serves an increasingly complex patient population and provides
      the majority of elective surgeries, and adapting some of the transition tools
      that have been tested in other settings will benefit health care providers and
      patients in the ambulatory setting. Identifying periods of transition and risk,
      implementing electronic health records across all phases of patient care, and
      using evidence-based tools at each transitional stage can optimize the quality
      and safety of patient care.

PMID- 21967909
TI  - The effectiveness and cost of passive warming in adult ambulatory surgery
      patients.
AB  - Hypothermia is a common problem for surgical patients and can result in many
      complications. Because few studies compare methods of passive warming, we used an
      unblinded, prospective, experimental, randomized design to compare the
      effectiveness of two passive methods of normothermia management in the
      postanesthesia care unit (PACU). We assigned a total of 578 adult ambulatory
      surgery patients to either a control group that was given two folded, warmed
      cotton blankets or a treatment group that was given a warmed, unfolded cotton
      sheet and cotton blanket. We recorded patients' temperatures on their arrival in
      the PACU and at 30 minutes after arrival. The treatment group had temperatures
      that were significantly higher than those of the control group 30 minutes after
      arrival in the PACU, and the treatment group experienced a greater change in
      temperature from baseline measurements to those taken at 30 minutes. The
      treatment group also used fewer warmed blankets, resulting in cost savings for
      the PACU.

PMID- 21967910
TI  - Using games to provide interactive perioperative education.
AB  - Perioperative nurses must use critical thinking and sound clinical judgment to
      meet their patients' needs safely and effectively. This requires the integration
      and continual updating of large amounts of detailed clinical information.
      Innovative education strategies are designed to make teaching and learning more
      interesting and interactive, especially for the presentation of complex subject
      material. One interactive educational strategy is the use of games. Educational
      games can foster collaboration and critical thinking among peers and associates.
      An example of this was the Perioperative QuizBowl: Evidence-Based Practice
      presented at the annual AORN Congress from 2003 to 2010, which was used to teach
      and reinforce evidence-based practice in a fun, competitive way. Although AORN no
      longer presents this offering, the QuizBowl format demonstrates how educational
      games can support clinical practice.

PMID- 21967911
TI  - Meeting the challenge of perioperative education.
AB  - The staffing challenges faced by perioperative nurse managers today are not
      easily met by waiting for experienced perioperative nurses to apply for
      positions. As Baby Boomer nurses retire, managers must consider hiring and
      orienting new graduates and nurses experienced in other subspecialties who are
      interested in working in the OR. An effective didactic and clinical education
      program can produce nurses with a basic perioperative knowledge from which they
      can build a solid clinical practice. Using Periop 101: A Core CurriculumTM, the
      director of perioperative services at a level II trauma center implemented a
      successful program to solve a staffing need and help students gain the knowledge
      and skills necessary to become effective perioperative nurses. Strong interest
      from capable applicants, a dedicated educator, and financial resources and
      support from hospital administrators helped make this program a viable way to
      staff the OR.

PMID- 21967912
TI  - Nurse liaison: the bridge between the perioperative department and patient
      accompaniers.
AB  - The role of the perioperative nurse liaison at Hadassah-Hebrew University Medical
      Center, Ein Kerem in Jerusalem, Israel, is to provide information and help
      patients' family members and others accompanying surgical patients cope with
      feelings of uncertainty, emotional stress, and fear. The nurse liaison is
      responsible for ongoing communication with patient accompaniers awaiting the
      conclusion of surgery and, in particular, for updating them on the surgery's
      progress. As part of a quality assurance project, the OR academic assistant, the
      OR nursing supervisor, and the coordinator of clinical quality and assurance in
      nursing conducted a quantitative descriptive survey to evaluate patient
      accompaniers' satisfaction with the updates provided by the nurse liaison
      throughout surgery and with the waiting room conditions. Results indicated that
      the nurse liaison makes a significant contribution to the welfare of patient
      accompaniers during surgery. In addition, results showed a need to improve the
      waiting room conditions to allow for more privacy.

PMID- 21967914
TI  - Benchmarking for better outcomes.

PMID- 21967913
TI  - Complying with the bloodborne pathogen standard: protecting health care workers
      and patients.

PMID- 21967915
TI  - Changing perioperative practice in an Indonesian hospital: part I of II.

PMID- 21967918
TI  - Do-not-resuscitate orders in the OR and afterward.

PMID- 21967919
TI  - Progressive multifocal leukoencephalopathy with wallerian degeneration.

PMID- 21967920
TI  - Treatment as prevention: preparing the way.
AB  - Potent antiretroviral therapy (ART) reduces mortality and morbidity in people
      living with HIV by reducing viral load and allowing their immune systems to
      recover. The reduction in viral load soon after starting ART has led to the
      hypothesis that early and widespread ART could prevent onward transmission and
      therefore eliminate the HIV epidemic in the long term. While several authors have
      argued that it is feasible to use HIV treatment as prevention (TasP), provided
      treatment is started sufficiently early, others have reasonably drawn attention
      to the many operational difficulties that will need to be overcome if the
      strategy is to succeed in reducing HIV transmission. Furthermore, international
      public health policy must be based on more than theoretical studies, no matter
      how appealing. Community randomized controlled trials provide the gold standard
      for testing the extent to which early treatment reduces incidence, but much still
      needs to be understood and the immediate need is for operational studies to
      explore the practical feasibility of this approach. Here, we examine some of the
      issues to be addressed, the obstacles to be overcome, and strategies that may be
      necessary if TasP is to be effective. Studies of this kind will provide valuable
      information for the design of large-scale trials, as well as essential
      information that will be needed if early treatment is to be incorporated into
      public health policy.

PMID- 21967921
TI  - Intra-abdominal pulmonary sequestration: a case report and literature review.
AB  - Pulmonary sequestration is a rare congenital malformation mostly located in the
      thorax, while intra-abdominal pulmonary sequestration is an extremely rare type
      of pulmonary sequestration usually diagnosed during the first 6 months of life.
      Only 1 case of intra-abdominal pulmonary sequestration in a patient older than 60
      years has been reported in the current literature. It is difficult to
      differentiate an intra-abdominal pulmonary sequestration from other
      retroperitoneal tumors. A definitive diagnosis is always made by histological
      examination. Intra-abdominal pulmonary sequestration commonly responds well to
      surgical resection and is associated with excellent results and prognosis. The
      authors present the case of a 74-year-old asymptomatic man with a retroperitoneal
      mass which was completely excised and revealed by histopathological study to be
      an intra-abdominal pulmonary sequestration.

PMID- 21967922
TI  - Who determines when orthodontic treatment is complete?

PMID- 21967924
TI  - The key to success is not the TSAD alone.

PMID- 21967926
TI  - Evaluating root resorption lesions with CBCT.

PMID- 21967928
TI  - Recovery after third molar surgery: the effects of phases of the menstrual cycle.

PMID- 21967929
TI  - When to say no.

PMID- 21967931
TI  - Palatal expansion in adults: the nonsurgical approach.

PMID- 21967932
TI  - Palatal expansion in adults: the surgical approach.

PMID- 21967933
TI  - Effects of latency on the quality and quantity of bone produced by dentoalveolar
      distraction osteogenesis.
AB  - INTRODUCTION: Infrabony defects in the alveolus pose a substantial treatment
      complication for restorative dentists. The properties of regenerate bone produced
      by dentoalveolar distraction, with and without a latency period, remain largely
      unknown. METHODS: Six male foxhound dogs between 1 and 2 years of age underwent
      osteotomies around the mandibular second premolar to create a dentoalveolar
      segment that was distracted (1 mm/day for 10 days) through a large periodontal
      defect created in the third premolar area. A split-mouth design was used, with 1
      randomly selected side starting distraction immediately, and the other side
      starting distraction after a 5-day latency period. The nonlatency and latency
      sides had 7 and 6 weeks of consolidation, respectively. Microcomputed tomography
      scans (taken at 15 and 60 MUm) were used to evaluate bone quality and quantity of
      the regenerate bone, as well as the maturational differences in the regenerate.
      RESULTS: The transport segments were distracted 7 to 8 mm over 10 days. The
      majority (>75%) of the specimens showed complete or almost complete vertical and
      buccolingual bone fill. Except for trabecular separation, there were no
      significant differences between the latency and nonlatency sides in the quantity
      or quality of bone produced. Although relative bone volume tended to increase
      between the mesial and distal aspects of the regenerate, there were no
      significant differences in material properties in the regenerate. The control
      bone was denser and greater in quantity than the regenerate bone. CONCLUSIONS:
      Except for slight differences in maturation, latency had little or no effect on
      the regenerate bone produced. Dentoalveolar distraction immediately after
      alveolar bone surgery appears to produce bone of adequate quantity and quality
      for dental implant restorations.

PMID- 21967934
TI  - Depth of resin penetration into enamel with 3 types of enamel conditioning
      methods: a confocal microscopic study.
AB  - INTRODUCTION: The clinical efficiency of a bonding material relies on its bond
      strength and debonding characteristics; the depth of resin penetration into
      enamel affects both of these factors. The depth of resin penetration has been
      previously studied by researchers using laborious, indirect methods, including
      the scanning electron microscope and the optical microscope. METHODS: We used a
      more direct method, confocal microscopy, to visualize the resin tags in enamel.
      Thirty maxillary first premolars were selected and divided into 3 groups. In
      group A, the buccal enamel surfaces were conditioned with 37% phosphoric acid; in
      group B, a self-etching primer was used; and group C was treated with air
      abrasion. Transbond XT adhesive (3M Unitek, Monrovia, Calif) was used to bond a
      modified bracket. Transbond XT primer (3M Unitek) mixed with rhodamine B
      fluorescent dye (Chennai Chemicals, Chennai, India) was applied in groups A and
      C. In group B, rhodamine was mixed with self-etching primer. After curing, the
      brackets were debonded, and the teeth were visualized under the fluorescent
      channel of the confocal microscope. RESULTS: Maximal resin penetration of 53.9
      MUm was observed in group A, followed by group B at 40.5 MUm and group C at 39.9
      MUm. CONCLUSIONS: Confocal microscope evaluation showed that enamel conditioning
      with 37% phosphoric acid produced greater depths of resin penetration than did
      self-etching primer or air abrasion.

PMID- 21967935
TI  - Craniofacial growth variations in nasal-breathing, oral-breathing, and
      tracheotomized children.
AB  - INTRODUCTION: Childhood oral breathing can alter muscular balance and lead to
      facial deformities. No articles in the literature have reported on the alteration
      of facial growth patterns in patients who have received tracheotomies. The
      purpose of this study was to evaluate craniofacial developmental consequences
      originating from variations in breathing mechanisms in children who are nasal
      breathers or oral breathers, and those who have been tracheotomized. METHODS: The
      sample was divided into 3 groups of 10 each. The nasal group had a mean age of
      13.9 years, the oral group had a mean age of 12.7 years, and the tracheotomy
      group had a mean age of 12.8 years. The masseter and suprahyoid muscles were
      evaluated with electromyography. The following measurements were made: facial,
      maxillary, and mandibular widths; nasion-sella-gnathion angle; and facial index.
      RESULTS: The tracheotomized group was similar to the nasal group for greater
      activity of the masseter muscles than of the suprahyoid muscles during
      mastication, as well as in the measurements of facial, maxillary, and mandibular
      widths. The oral group showed reductions in each category. The tracheotomized
      group was similar to the oral group during maximum dental occlusion for
      significantly higher activity of the suprahyoid muscles compared with the
      masseter muscles, with reductions in vertical values. CONCLUSIONS: A childhood
      tracheotomy might affect facial development in a way comparable with that of oral
      breathers, including abnormal facial growth variations.

PMID- 21967936
TI  - Stability of rapid maxillary expansion and facemask therapy: a long-term
      controlled study.
AB  - INTRODUCTION: The aim of this prospective controlled study was to evaluate the
      long-term effects of rapid maxillary expansion and facemask therapy in Class III
      subjects. METHODS: Twenty-two subjects (9 boys, 13 girls; mean age, 9.2 years +/-
      1.6) with Class III disharmony were treated consecutively with rapid maxillary
      expansion and facemask therapy followed by fixed appliances. The patients were
      reevaluated at the end of the 2-phase treatment (mean age, 14.5 years +/- 1.9)
      and then recalled about 8.5 years after the end of rapid maxillary expansion and
      facemask treatment (mean age, 18.7 years +/- 2.1). Two groups of controls with
      untreated Class III malocclusion were used for statistical comparisons of the
      short-term and long-term intervals. Statistical comparisons were performed with
      the Mann-Whitney U test. RESULTS: In the long term, no significant differences in
      maxillary changes were recorded, whereas the treatment group showed significantly
      smaller increases in mandibular protrusion. The sagittal maxillomandibular
      skeletal variables maintained significant improvements in the treatment group vs
      the control groups. CONCLUSIONS: In the long term, rapid maxillary expansion and
      facemask therapy led to successful outcomes in about 73% of the Class III
      patients. Favorable skeletal changes were mainly due to significant improvements
      in the sagittal position of the mandible.

PMID- 21967937
TI  - Biodegradation of orthodontic metallic brackets and associated implications for
      friction.
AB  - INTRODUCTION: This study aimed to assess the effect of clinical exposure on the
      surface morphology, dimensions, and frictional behavior of metallic orthodontic
      brackets. METHODS: Ninety-five brackets, of 3 commercial brands, were retrieved
      from patients who had finished orthodontic treatment. As-received brackets,
      matched by type and brand, were used for comparisons. Surface morphology and
      precipitated material were analyzed by optical and scanning electron microscopy
      and x-ray microanalysis. Bracket dimensions were measured with a measuring
      microscope. Resistance to sliding on a stainless steel wire was assessed.
      RESULTS: Retrieved brackets showed surface alterations from corrosion, wear, and
      plastic deformation, especially in the external slot edges. Film deposition over
      the alloy surface was observed to a variable extent. The main elements in the
      film were carbon, oxygen, calcium, and phosphorus. The as-received brackets
      showed differences (P <0.05) in the slot sizes among brands, and 1 brand showed a
      3% increase in the retrieved brackets' slots. The frictional behavior differed
      among brands. Retrieved brackets of 2 brands showed 10% to 20% increases in
      resistance to sliding. CONCLUSIONS: Metallic brackets undergo significant
      degradation during orthodontic treatment, possibly with increased friction. At
      present, it is difficult to predict the impact of these changes on the clinical
      performance of orthodontic components.

PMID- 21967939
TI  - Evaluation of retention protocols among members of the American Association of
      Orthodontists in the United States.
AB  - INTRODUCTION: Little research has been conducted to evaluate protocols and trends
      in orthodontic retention. The purpose of this study was to identify the general
      retention protocols used by orthodontists in the United States. Additionally, our
      goal was to identify trends in these orthodontic retention protocols by
      evaluating how they have changed over the past 5 years and how they might
      continue to change in the next 5 years. METHODS: The study was conducted via a 36
      question electronic survey (REDCap, Nashville, Tenn) with branching logic on
      certain questions. The survey was sent to all 9143 practicing members of the
      American Association of Orthodontists in the United States, and 1632 (18%)
      responded. RESULTS AND CONCLUSIONS: Mean retention protocols of the surveyed
      population showed predominant use of Hawley or vacuum-formed retainers in the
      maxillary arch and fixed retention in the mandibular arch. For both arches, there
      is a current shift away from Hawley retainers and toward vacuum-formed retainers
      and fixed retention. Respondents who extract fewer teeth reported increased use
      of fixed retention in the maxillary (P = 0.041) and mandibular (P = 0.003)
      arches. Respondents who extract fewer teeth and use removable retainers were more
      likely to tell their patients to wear their retainers at night for the rest of
      their lives (P = 1.63 * 10(-6)).

PMID- 21967938
TI  - Effects of rapid maxillary expansion on the cranial and circummaxillary sutures.
AB  - INTRODUCTION: The aim of this study was to determine whether the orthopedic
      forces of rapid maxillary expansion cause significant quantitative changes in the
      cranial and the circummaxillary sutures. METHODS: Twenty patients (mean age, 12.3
      +/- 1.9 years) who required rapid maxillary expansion as a part of their
      comprehensive orthodontic treatment had preexpansion and postexpansion computed
      tomography scans. Ten cranial and circummaxillary sutures were located and
      measured on one of the axial, coronal, or sagittal sections of each patient's
      preexpansion and postexpansion computed tomography scans. Quantitative variables
      between the 2 measurements were compared by using the Wilcoxon signed rank test.
      A P value less than 0.05 was considered statistically significant. RESULTS: Rapid
      maxillary expansion produced significant width increases in the intermaxillary,
      internasal, maxillonasal, frontomaxillary, and frontonasal sutures, whereas the
      frontozygomatic, zygomaticomaxillary, zygomaticotemporal, and pterygomaxillary
      sutures showed nonsignificant changes. The greatest increase in width was
      recorded for the intermaxillary suture (1.7 +/- 0.9 mm), followed by the
      internasal suture (0.6 +/- 0.3 mm), and the maxillonasal suture (0.4 +/- 0.2 mm).
      The midpalatal suture showed the greatest increase in width at the central
      incisor level (1.6 +/- 0.8 mm) followed by the increases in width at the canine
      level (1.5 +/- 0.8 mm) and the first molar level (1.2 +/- 0.6 mm). CONCLUSIONS:
      Forces elicited by rapid maxillary expansion affect primarily the anterior
      sutures (intermaxillary and maxillary frontal nasal interfaces) compared with the
      posterior (zygomatic interface) craniofacial structures.

PMID- 21967940
TI  - Effect of fluoridated paste on the failure rate of precoated brackets bonded with
      self-etching primer: a prospective split-mouth study.
AB  - INTRODUCTION: The aim of this prospective randomized clinical trial was to
      determine the effect of using fluoridated paste (Dentsply, York, Pa) compared
      with plain pumice (Ortho Technology, Tampa, Fla) on the clinical bond failure
      rates of precoated brackets bonded with self-etching primer. METHODS: A split
      mouth technique was used. The teeth in the maxillary right and mandibular left
      quadrants were prepared with a fluoridated paste only, and the teeth in the
      maxillary left and mandibular right quadrants were prepared with plain pumice
      before bonding the precoated brackets. A total of 627 brackets in 34 orthodontic
      patients (20 female, 14 male) were included in this study; 315 brackets were
      bonded after pumice treatment, and 312 were bonded after paste treatment. The
      patients were followed for 6 months to determine the rates of bracket failure.
      RESULTS: The overall failure rate was 8%. The failure rates for pumice and paste
      were 4.8% and 11.2%, respectively. The McNemar test showed a statistically
      significant difference between the 2 groups. Based on tooth type, the failure
      rate of the maxillary canine and the mandibular central incisor brackets were
      significantly different for paste and pumice. There was also a difference in the
      survival rates of the brackets in both groups. CONCLUSIONS: Preparation of the
      enamel surface with fluoridated paste before bonding with self-etching primer is
      not recommended. However, the use of plain pumice is recommended, even if it is
      time-consuming.

PMID- 21967941
TI  - Comparison of deformation of 3 orthodontic miniplate lever arms.
AB  - INTRODUCTION: Deflections of the lever arms on 3 commercially available
      miniplates (Stryker, Kalamazoo, Mich; KLS Martin, Tuttlingen, Germany; and
      Synthes, West Chester, Pa) were compared to determine whether orthopedic forces
      produce permanent deformation. METHODS: Thirty-six miniplates were tested on a
      load frame in this ex-vivo trial. The force level at which permanent deformation
      occurred was measured. The arms of the miniplates were extended beyond the force
      level needed for orthopedic anchorage. RESULTS: Load-displacement data followed
      an expected trend from beam theory, where a linear region of elastic response was
      followed by an elastic-plastic transition to fully plastic deformation. The yield
      was measured at the beginning of the nonlinear response. Beam bending analysis
      was used to determine the yield stress of each sample and to estimate the elastic
      modulus. In some cases, the calculated yield stresses were higher and the modulus
      of elasticity was lower than the reported values for titanium. This was due to
      the torsion in the testing. Loads at the point of initial yielding ranged from
      1280 to 3000 g, depending on the miniplate type. Stryker's yield was
      statistically lower than that for KLS Martin and Synthes, which were well above
      the ranges needed for orthopedic forces. CONCLUSIONS: All 3 miniplates were
      capable of withstanding orthopedic forces. The 3 brands had significant
      differences in modulus of elasticity values, which were lower than published
      values.

PMID- 21967942
TI  - Comparison of the antimicrobial activity of Listerine and Corsodyl on orthodontic
      brackets in vitro.
AB  - INTRODUCTION: The aim of this study was to evaluate the antimicrobial efficacy of
      2 commercially available mouth rinses on a monospecies-biofilm model on
      orthodontic brackets in vitro. METHODS: The antimicrobial effects of the 2 mouth
      rinses, Listerine (tartar control; IDS Manufacturing, Bangkok, Thailand) and
      Corsodyl (SmithKline Beecham, Maidenhead, United Kingdom), on the planktonic
      Streptococcus mutans were tested by maximum inhibitory dilution assay. The cell
      viability of S mutans biofilm on Damon3 MX brackets (Ormco, Glendora, Calif)
      after exposure to the 2 mouth rinses was quantified by 2,3-bis (2-methoxy-4-nitro
      5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide (XTT)
      reduction assay. Visualization of the biofilm samples was performed by
      fluorescence microscopy and confocal laser scanning microscopy. RESULTS: The
      maximum inhibitory dilution assays of S mutans were 1:5 for Listerine and 1:320
      for Corsodyl. The optical density values, which were measured by XTT reduction
      assay from S mutans biofilms after 1 minute of exposure to the different test
      agents, demonstrated that the cell viability of S mutans biofilms exposed to
      Listerine was less than that for Corsodyl, which was less than that for brain
      heart infusion (P <0.001). Listerine caused more dead cells on the surface of the
      brackets than did Corsodyl when examined with the 2 microscope systems.
      CONCLUSIONS: Both mouth rinses showed marked antimicrobial effects on the
      monospecies biofilm in vitro. Listerine showed a stronger bactericidal effect but
      had less bacterial inhibitory effect than did Corsodyl.

PMID- 21967943
TI  - Sex differences in the uptake of orthodontic services among adolescents in the
      United States.
AB  - INTRODUCTION: The purpose of this study was to test whether girls are treated
      orthodontically for milder occlusal issues than are boys, thus accounting for the
      greater uptake of orthodontic services among girls compared with boys. METHODS:
      The dental aesthetic index (DAI) was used to score the severity of esthetic
      occlusal issues in 357 white adolescents. Half of the subjects were from private
      practices; the others were from a university specialty clinic. RESULTS: Average
      DAI scores were statistically significantly lower (milder) in girls than boys in
      both venues; this confirms the assumption that the actual uptake of services is
      greater in girls because of heightened concern for their esthetic occlusal
      issues. Average DAI scores predictably were higher in the teaching setting
      because of selection for more complex cases, but the sex difference was still
      evident statistically. There was no association between DAI score and age at the
      start of treatment among these adolescents. Spacing and incisor irregularity
      showed the greatest sex differences among the DAI variables, possibly because
      girls are more attuned to these esthetic issues. CONCLUSIONS: These results
      complement studies that have recorded adolescents' perceptions of orthodontic
      need. The actual uptake of orthodontic treatment is greater in girls because they
      (and their parents) seek treatment for milder occlusal issues.

PMID- 21967944
TI  - Long-term stability of LeFort III distraction osteogenesis with a rigid external
      distraction device in a patient with Crouzon syndrome.
AB  - A 6-year-old boy, diagnosed with Crouzon syndrome, had moderate exorbitism, a
      concave profile, an anterior crossbite of -4.0 mm, and a skeletal Class III jaw
      base relationship caused by midfacial hypoplasia. At age 8 years 9 months, a
      LeFort III osteotomy was performed, and distraction osteogenesis was immediately
      started with the rigid external distractor system. The midface was advanced
      approximately 10.0 mm for 6 days, including overcorrection. After the
      distraction, a reverse headgear was used for 6 years to prevent relapse and to
      accelerate expected growth. At age 16 years 5 months, after extraction of the
      maxillary first premolars and mandibular third molars, 0.022-in preadjusted
      edgewise brackets were placed to treat the edge-to-edge incisor relationship and
      minor crowding. After 13 months of treatment, the facial profile was
      significantly improved, and an acceptable occlusion was achieved. During the 9
      year observation period after the distraction, acceptable facial growth occurred,
      and no relapse of the maxillary advancement was observed. However, syndrome
      specific growth and methodologically induced relapse should be considered when
      planning a LeFort III distraction in children for the treatment of Crouzon
      syndrome.

PMID- 21967945
TI  - Orthodontic treatment of a patient with Lowe syndrome.
AB  - This article describes the orthodontic treatment of a patient with Lowe syndrome.
      The objective of the treatment was to improve the patient's dental relationships
      and consequently his quality of life. This was achieved by maxillary expansion
      and extraction of the mandibular central incisors and maxillary deciduous
      canines. The teeth were aligned and leveled with a fixed orthodontic appliance.
      Satisfactory results were obtained at the end of treatment, with substantial
      improvement in dental esthetics, occlusal function, and facial profile.

PMID- 21967946
TI  - Novel application of the 2-piece orthodontic C-implant for temporary crown
      restoration after orthodontic treatment.
AB  - INTRODUCTION: This article reports the use of an orthodontic mini-implant for a
      temporary crown restoration in a small edentulous space after limited orthodontic
      treatment. METHODS: Two clinical cases are presented: a 23-year-old woman and a
      14-year-old boy. In the adult patient, a 2-piece orthodontic C-implant (Cimplant,
      Seoul, Korea) was placed in a 3-mm wide edentulous space to build up a temporary
      crown restoration after a short orthodontic treatment to regain space for a
      missing mandibular right permanent lateral incisor. In the boy, a C-implant was
      placed in the space resulting from an avulsed maxillary right permanent lateral
      incisor to prevent aggressive alveolar bone resorption after dental trauma. Both
      patients were followed for more than 4 years of retention to evaluate the
      stability of the temporary crown restoration built up on the orthodontic mini
      implants. RESULTS: Both patients had successful long-term results, confirmed by
      clinical and radiographic examinations. Both were pleased with the results and
      plan to retain the orthodontic mini-implant temporary crown restoration until
      they are ready for a permanent restoration later. CONCLUSIONS: A 2-piece
      orthodontic C-implant system can be used to maintain edentulous space after
      active orthodontic treatment.

PMID- 21967947
TI  - Multiple hyperdontia: Report of an unusual case.
AB  - Supernumerary teeth are an infrequent developmental anomaly that can appear in
      any area of the dental arch and can affect any dental organ. Multiple
      supernumerary teeth, or hyperdontia, is rare in people with no other associated
      diseases or syndromes. Conditions commonly associated with hyperdontia include
      cleft lip and palate, trichorhinophalangeal syndrome, cleidocranial dysplasia,
      and Gardner's syndrome. A black girl, aged 11 years 8 months, came for
      consultation; radiographs showed 81 teeth: 18 deciduous, 32 permanent, and 31
      supernumerary. The main concern initially was to determine whether she was
      syndromic, and she was referred to a geneticist. G banding analysis showed
      pericentric inversion of chromosome 9; the chromosome formula was 46, XX, inv (9)
      (p13q21). Orthodontic treatment for this patient will be a clinical challenge
      because of the great number of teeth to be extracted and the alterations in the
      shapes of the teeth. Treatment goals should be established by a multidisciplinary
      team, where oral surgeon, orthodontist, periodontist, and prosthodontist come
      together to solve a medical and dental puzzle, eliminating the pieces that do not
      fit and searching for new ones to obtain an occlusion that will give the patient
      physiologic conditions of normality and esthetic satisfaction.

PMID- 21967948
TI  - Registration accuracy in the integration of laser-scanned dental images into
      maxillofacial cone-beam computed tomography images.
AB  - INTRODUCTION: A precision 3-dimensional (3D) head model can be fabricated by
      integrating a digital dental model into a maxillofacial 3D image. The integration
      requires accurate registration of 2 image modalities. The aims of this study were
      to determine the registration errors for implementation of laser-scanned dental
      images into cone-beam computed tomography (CBCT) scan data and to examine the
      influence of the registration area on the accuracy of registration. METHODS: The
      CBCT scans were obtained from 30 adults, and the maxillofacial 3D images were
      reconstructed. Maxillary and mandibular dental casts were taken from the same
      subjects and scanned with a 3D laser scanner. The laser-scanned maxillary and
      mandibular dentition images were incorporated into the CBCT images of each arch
      in 3 ways according to the registration area: only the buccal surfaces, only the
      lingual surfaces, and both the buccal and lingual surfaces. Surface-based
      registration was performed by using an iterative closest point algorithm, and its
      errors were evaluated by measuring the 3D Euclidean distances between the surface
      points on the 2 images. RESULTS: The registration errors ranged from 0.27 to 0.33
      mm. The mandibular arch did not show significant differences in registration
      errors according to the selected area for the registration. The maxillary arch,
      however, showed significant differences according to the registration area. When
      the lingual surfaces only were used for registration, the errors were greater
      than for the other 2 methods. The errors were least when both the buccal and
      lingual surfaces were used for registration. CONCLUSIONS: The results of this
      study indicate that accuracy in the integration of laser-scanned dental images
      into the maxillofacial CBCT images increases when a broad area is used for
      registration.

PMID- 21967949
TI  - Litigation, legislation & ethics. Can you hear me now?

PMID- 21967950
TI  - Sources of bias in clinical trials.

PMID- 21967951
TI  - Sample size estimation: an overview with applications to orthodontic clinical
      trial designs.
AB  - Proper sample size estimation is an important part of clinical trial methodology
      and closely related to the precision and power of the trial's results. Trials
      with sufficient sample sizes are scientifically and ethically justified and more
      credible compared with trials with insufficient sizes. Planning clinical trials
      with inadequate sample sizes might be considered as a waste of time and
      resources, as well as unethical, since patients might be enrolled in a study in
      which the expected results will not be trusted and are unlikely to have an impact
      on clinical practice. Because of the low emphasis of sample size calculation in
      clinical trials in orthodontics, it is the objective of this article to introduce
      the orthodontic clinician to the importance and the general principles of sample
      size calculations for randomized controlled trials to serve as guidance for study
      designs and as a tool for quality assessment when reviewing published clinical
      trials in our specialty. Examples of calculations are shown for 2-arm parallel
      trials applicable to orthodontics. The working examples are analyzed, and the
      implications of design or inherent complexities in each category are discussed.

PMID- 21967952
TI  - Effect of a self-etching adhesive containing an antibacterial monomer on clinical
      periodontal parameters and subgingival microbiologic composition in orthodontic
      patients.
AB  - INTRODUCTION: The aims of this study were to evaluate the effect of a self
      etching adhesive system containing an antibacterial monomer on periodontal health
      and subgingival microbiologic composition in orthodontic patients and to compare
      it with a conventional adhesive system. METHODS: A split-mouth design was chosen,
      and 15 patients were included in the study. Brackets in contralateral quadrants
      were bonded with either a conventional adhesive system (control) or a self
      etching adhesive system that contained an antibacterial monomer. Clinical
      periodontal parameters including plaque index, gingival index, probing depths,
      and bleeding on probing were determined. Subgingival plaque samples were
      collected before bracket placement (T0) and at the 6-month follow-up (T1). The
      real-time TaqMan polymerase chain reaction assay was used to determine the
      subgingival counts of Porphyromonas gingivalis, Tannerella forsythensis,
      Prevotella intermedia, Aggregatibacter actinomycetemcomitans, Fusobacterium
      nucleatum, and Campylobacter rectus. For clinical periodontal parameters,
      analysis of covariance (ANCOVA) and, for bacterial counts, Wilcoxon tests were
      used for statistical comparisons at the P <0.05 level. RESULTS: Clinical
      periodontal parameters were not changed, and they were not different between the
      groups from T0 to T1. T forsythensis and F nucleatum increased during the
      treatment period in both groups (P <0.05). The majority of the bacteria were T
      nucleatum at T0 and T1 in both groups. Changes in bacterial load from T0 to T1
      were not different between groups except for T forsythensis and F nucleatum (P
      <0.05). CONCLUSIONS: The use of an antibacterial monomer did not have an
      additional positive effect on clinical periodontal parameters. When used in
      bonding orthodontic brackets, the antibacterial monomer failed to reduce
      periodontopathogenic bacteria when compared with the conventional adhesive system
      during a 6-month treatment period.

PMID- 21967953
TI  - Effect of early Class II treatment on the incidence of incisor trauma.
AB  - INTRODUCTION: Many researchers have examined the prevalence of dental injuries in
      children and adolescents. The purpose of this study was to examine the prevalence
      and incidence of incisor trauma in subjects who participated in a randomized
      clinical trial designed to investigate early growth modifications in the
      treatment of Class II malocclusion. METHODS: The subjects were randomized to 3
      treatment groups during the initial phase of the study: (1) headgear or
      biteplane, (2) bionator, and (3) observation (no treatment). All 3 groups
      underwent phase 2 treatment with fixed appliances. Incisor injury was scored at
      every data collection point with the Ellis index by a blinded examiner using
      dental casts, intraoral photos, and panoramic and periapical x-rays. RESULTS:
      Twenty-five percent of the subjects had incisor trauma at the baseline
      examination, and 28% experienced new or worsening maxillary incisor injury during
      the study. No significant differences were found with regard to sex and
      prevalence of injury at baseline. No differences in incidence of trauma were
      found between the 3 treatment groups throughout the study (P = 0.19); however,
      boys were more likely to experience maxillary incisor injury (odds ratio
      estimate, 2.37; 95% CI, 1.33, 4.21), and those with an injury at baseline were
      more likely to experience an additional injury (odds ratio estimate, 1.81; 95%
      CI, 1.03, 3.17). CONCLUSIONS: Early orthodontic treatment did not affect the
      incidence of incisor injury. The majority of the injuries before and during
      treatment were minor; therefore, the cost-benefit ratio of orthodontic treatment
      primarily to prevent incisor trauma is unfavorable.

PMID- 21967954
TI  - Three-dimensional analysis of pharyngeal airway volume in adults with anterior
      position of the mandible.
AB  - INTRODUCTION: The purpose of this study was to examine whether the pharyngeal
      airway volume in adults with skeletal Class III malocclusion is greater than in
      subjects with Class I occlusion and whether the pharyngeal airway volume
      correlated with facial morphology. METHODS: Cone-beam computed tomography scans
      were obtained from 60 subjects, who were assigned to 2 groups. The skeletal Class
      III malocclusion group consisted of 31 subjects (16 men, 15 women) who had
      planned on orthodontic treatment with orthognathic surgery. The Class I
      malocclusion group consisted of 29 subjects (14 men, 15 women). The pharyngeal
      airway volumes and areas were measured and compared with cephalometric variables.
      RESULTS: The cross-sectional areas of the lower part of the pharyngeal airway and
      the volume of the upper part of the pharyngeal airway were greater in skeletal
      Class III malocclusion patients than in Class I malocclusion patients. The volume
      of the upper part of the pharyngeal airway showed negative correlations with ANB
      angle and the Wits appraisal, and positive correlations with SNB, APDI, pogonion
      to N-perp, gonial angle, and FMA. CONCLUSIONS: The volume of the upper part of
      the pharyngeal space was greater in patients with skeletal Class III
      malocclusion, and the increased volume of the upper part of the pharyngeal airway
      showed significant correlations with measurements characterizing the anterior
      position of mandible.

PMID- 21967955
TI  - Smile esthetics from patients' perspectives for faces of varying attractiveness.
AB  - INTRODUCTION: Delivering an attractive smile is a key element in orthodontic
      patient satisfaction. Smile characteristics can be affected by the facial
      context. The purpose of this study was to investigate smile esthetics related to
      facial attractiveness and sex of the model. METHODS: Attractive, average, and
      unattractive model faces (2 of each; 3 male, 3 female) determined by peer ratings
      were combined with 10 smile variables (buccal corridor, smile arc, maxillary
      gingival discrepancy, gingival display, incisal-edge discrepancy, cant, overbite,
      central-incisor gingival margin discrepancy, and maxillary midline to face, and
      maxillary midline to mandibular midline). Each smile characteristic was altered
      digitally and presented with slider technology to allow a continuous range of
      choices. Raters chose the ideal and the limits of acceptability. The variables
      were divided into 6 separate surveys and rated 96 times. Reliability was assessed
      by answering each question twice. RESULTS: Individual smile variable reliability
      ranged from fair to excellent, except for the buccal corridor. Clinically
      significant values were defined as greater than 1.0 mm with statistical
      significance (P <0.05). Rater sex did not make a difference. Clinical
      significance was found for smile arc, gingival display, and maxillary midline to
      face. For females, accentuated smile arcs were preferred for the unattractive and
      attractive models compared with the average models. The opposite was found for
      male models. More gingival display was preferred for the attractive and
      unattractive male and female models compared with the average models. Attractive
      models were allowed less midline deviation. CONCLUSIONS: Facial attractiveness
      and model sex impacted smile variables with a facial context, except for occlusal
      cant. These smile characteristics with a facial context should be considered when
      diagnosing and planning treatment for an orthodontic patient.

PMID- 21967956
TI  - Effect of mini-implant diameter on fracture risk and self-drilling efficacy.
AB  - INTRODUCTION: The aim of this study was to evaluate the effect of mini-implant
      diameter on fracture risk and self-drilling efficacy. METHODS: A sample of 405
      mini-implants with 9 diameters from 1.2 to 2.0 mm was used. Ten mini-implants of
      each diameter were placed in artificial bone, and 25 were placed in pig iliac
      bone to evaluate placement torque (PT) and axial placement load (APL), which
      represents self-drilling efficacy. Ten mini-implants of each diameter were used
      to determine fracture torque (FT). The different diameters were compared
      regarding PT, FT, and APL. The fracture risk of each diameter was evaluated by
      the fracture resistance index (FT/PT * [FT-PT]). The PT and APL changes during
      placement were correlated. RESULTS: Only PT and FT were different for all mini
      implant diameter changes. PT and FT showed a strong correlation with the mini
      implant diameter, but the APL was weakly to moderately correlated. The fracture
      resistance index was remarkably greater for each 0.1 mm added in diameter. The PT
      increased significantly, whereas the APL was progressively reduced during
      placement. CONCLUSIONS: Increases in mini-implant diameters significantly
      influenced the increases of PT and FT on quantities that progressively reduced
      the fracture risk. The self-drilling efficacy was not strongly influenced by
      diameter.

PMID- 21967957
TI  - Biofilm retention by 3 methods of ligation on orthodontic brackets: a
      microbiologic and optical coherence tomography analysis.
AB  - INTRODUCTION: The aim of this study was to evaluate biofilm retention around
      orthodontic brackets related to the method of ligation by using optical coherence
      tomography (OCT) and microbiologic sampling. METHODS: Seventy-five plastic
      central incisors for dentures were divided into 3 groups and used with metal
      brackets with a 0.022-in slot with elastomeric ligature (n = 25), metal brackets
      with a 0.022-in slot with steel wire ligature (n = 25), and self-ligating
      brackets with a 0.022-in slot (n = 25). The samples were submersed in a
      suspension of Streptococcus mutans, genetically engineered to express green
      fluorescent protein, at 37 degrees C for 72 hours to allow biofilm formation. The
      samples were then submitted to microbiologic analysis and OCT imaging. RESULTS:
      The microbiologic analysis and the OCT showed significant differences in biofilm
      formation depending on the ligating method. Brackets ligated with elastomeric
      rings held more S mutans biofilm, and steel wire ligation had less biofilm
      retention compared with the other brackets. CONCLUSIONS: This study provided
      validation that OCT can be used as a potential qualitative marker of total plaque
      bacteria that can be rapidly and reliably visualized around orthodontic brackets.

PMID- 21967958
TI  - Reduced sleep spindles and spindle coherence in schizophrenia: mechanisms of
      impaired memory consolidation?
AB  - BACKGROUND: Sleep spindles are thought to induce synaptic changes and thereby
      contribute to memory consolidation during sleep. Patients with schizophrenia show
      dramatic reductions of both spindles and sleep-dependent memory consolidation,
      which may be causally related. METHODS: To examine the relations of sleep spindle
      activity to sleep-dependent consolidation of motor procedural memory, 21 chronic,
      medicated schizophrenia outpatients and 17 healthy volunteers underwent
      polysomnography on two consecutive nights. On the second night, participants were
      trained on the finger-tapping motor sequence task (MST) at bedtime and tested the
      following morning. The number, density, frequency, duration, amplitude, spectral
      content, and coherence of stage 2 sleep spindles were compared between groups and
      examined in relation to overnight changes in MST performance. RESULTS: Patients
      failed to show overnight improvement on the MST and differed significantly from
      control participants who did improve. Patients also exhibited marked reductions
      in the density (reduced 38% relative to control participants), number (reduced
      36%), and coherence (reduced 19%) of sleep spindles but showed no abnormalities
      in the morphology of individual spindles or of sleep architecture. In patients,
      reduced spindle number and density predicted less overnight improvement on the
      MST. In addition, reduced amplitude and sigma power of individual spindles
      correlated with greater severity of positive symptoms. CONCLUSIONS: The observed
      sleep spindle abnormalities implicate thalamocortical network dysfunction in
      schizophrenia. In addition, the findings suggest that abnormal spindle generation
      impairs sleep-dependent memory consolidation in schizophrenia, contributes to
      positive symptoms, and is a promising novel target for the treatment of cognitive
      deficits in schizophrenia.

PMID- 21967959
TI  - Reduced anterior cingulate cognitive activation is associated with prefrontal
      temporal cortical thinning in schizophrenia.
AB  - BACKGROUND: The anterior cingulate cortex plays a central role in altered
      processes of cognitive control in schizophrenia. However, the cortical
      foundations of disturbed anterior cingulate cognitive activation are poorly
      understood. Therefore, this study investigated the association of anterior
      cingulate cognitive activation and cortical thickness in schizophrenia combining
      functional magnetic resonance imaging (fMRI) and surface-based morphometry.
      METHODS: Fifty-three patients with schizophrenia according to DSM-IV and 53 age-
      and sex-matched healthy subjects were included and underwent fMRI and high
      resolution T1-weighted MRI. fMRI data was analyzed using SPM5. Cortical thickness
      was calculated using an automated computerized algorithm (Freesurfer Software).
      Statistical cortical maps were created correlating anterior cingulate activation
      and cortical thickness on a node-by-node basis covering the entire cortex in
      schizophrenia and healthy control subjects. RESULTS: Patients demonstrated a
      significantly reduced anterior cingulate cognitive activation. Significantly
      differing associations of anterior cingulate activation and cortical thickness
      were found in a pattern of dorsolateral prefrontal, superior frontal-anterior
      cingulate, and superior temporal cortical regions, where patients but not healthy
      control subjects demonstrated a significant association of reduced anterior
      cingulate activation and cortical thinning. A direct comparison of cortical
      thickness between the diagnostic groups revealed a significantly reduced cortical
      thickness of these prefrontotemporal regions in schizophrenia. CONCLUSIONS: To
      our best knowledge, this is the first study indicating that prefrontotemporal
      cortical thinning constitutes a relevant cortical pathomechanism for altered
      cognitive activation in schizophrenia. Our data additionally reveal a profound
      disruption of structural and functional integration in the prefrontotemporal
      system in schizophrenia.

PMID- 21967961
TI  - Charge equilibration force fields for molecular dynamics simulations of lipids,
      bilayers, and integral membrane protein systems.
AB  - With the continuing advances in computational hardware and novel force fields
      constructed using quantum mechanics, the outlook for non-additive force fields is
      promising. Our work in the past several years has demonstrated the utility of
      polarizable force fields, those based on the charge equilibration formalism, for
      a broad range of physical and biophysical systems. We have constructed and
      applied polarizable force fields for lipids and lipid bilayers. In this review of
      our recent work, we discuss the formalism we have adopted for implementing the
      charge equilibration (CHEQ) method for lipid molecules. We discuss the
      methodology, related issues, and briefly discuss results from recent applications
      of such force fields. Application areas include DPPC-water monolayers, potassium
      ion permeation free energetics in the gramicidin A bacterial channel, and free
      energetics of permeation of charged amino acid analogs across the water-bilayer
      interface. This article is part of a Special Issue entitled: Membrane protein
      structure and function.

PMID- 21967962
TI  - Differential gene expression between inbred Roman high- (RHA-I) and low- (RLA-I)
      avoidance rats.
AB  - Microarray technology was used to explore differences in brain gene expression
      under basal conditions in two strains of psychogenetically selected rats which
      differ in anxiety/stress responses, the inbred Roman High-(RHA-I) and Roman Low
      (RLA-I) Avoidance rats. Microarray analysis detected 14 up-regulated and 24 down
      regulated genes in RLA-I vs. RHA-I rats functionally related to neurobiological
      processes. The differentially expressed genes CAMKK2, CRHBP, EPHX2, HOMER3, NDN,
      PRL and RPL6 were selected for microarray validation using qRT-PCR. EPHX2, CAMKK2
      (both up-regulated in RLA-I vs. RHA-I rats) and HOMER3 (down-regulated in RLA-I
      vs. RHA-I rats) showed a similar tendency and fold-change both in microarray and
      RT-PCR analyses; PRL (up-regulated in RLA-I vs. RHA-I rats), CRHBP and RPL6 (both
      down-regulated in RLA-I vs. RHA-I animals) showed a similar tendency but a
      different order of magnitude of change among experiments; finally, NDN was
      validated neither in tendency nor in magnitude of change.

PMID- 21967963
TI  - TNF-alpha -308 G>A polymorphism and weight gain in patients with schizophrenia
      under long-term clozapine, risperidone or olanzapine treatment.
AB  - Atypical or second-generation antipsychotics (SGAs) are associated with excessive
      body weight gain (BWG) and other components of metabolic syndrome. Among all
      SGAs, clozapine and olanzapine are known to cause the most significant weight
      gain, followed by risperidone and quetiapine. The genetic variant of tumor
      necrosis factor alpha (TNF-alpha), -308 G>A polymorphism (rs1800629), has been
      implicated in clozapine-induced BWG in several studies. We hypothesized that TNF
      alpha -308 G>A polymorphism has a general effect on SGA-induced BWG. The present
      study was conducted to examine the association between TNF-alpha -308 G>A
      polymorphism and BWG during treatment for schizophrenia using a variety of second
      generation antipsychotics (SGAs). A total of 500 patients with schizophrenia
      treated with clozapine (n=275), olanzapine (n=79) or risperidone (n=146) for an
      average of 49.9 months were recruited. Subjects with an increase in weight of
      more than 7% from the baseline before the current SGA treatment to the weight at
      the survey point were defined as having BWG. The association between TNF-alpha 
      308 G>A polymorphism and BWG was studied, and the effect of non-genetic factors
      such as baseline BMI, SGA treatment duration and SGA type on the association was
      controlled by logistic regression. The results revealed that there was no
      significant association between BWG and TNF-alpha -308 G>A polymorphism (GG/GA/AA
      or GG/GA+AA) in each separate SGA group or collectively. These findings suggest
      that TNF-alpha -308 G>A polymorphism does not play a major role in SGA-induced
      weight gain.

PMID- 21967960
TI  - Gene therapy in the cornea: 2005--present.
AB  - Successful restoration of vision in human patients with gene therapy affirmed its
      promise to cure ocular diseases and disorders. The efficacy of gene therapy is
      contingent upon vector and mode of therapeutic DNA introduction into targeted
      cells/tissues. The cornea is an ideal tissue for gene therapy due to its ease of
      access and relative immune-privilege. Considerable progress has been made in the
      field of corneal gene therapy in last 5 years. Several new gene transfer vectors,
      techniques and approaches have evolved. Although corneal gene therapy is still in
      its early stages of development, the potential of gene-based interventions to
      treat corneal abnormalities has begun to surface. Identification of next
      generation viral and nanoparticle vectors, characterization of delivered gene
      levels, localization, and duration in the cornea, and significant success in
      controlling corneal disorders, particularly fibrosis and angiogenesis, in
      experimental animal disease models, with no major side effects have propelled
      gene therapy a step closer toward establishing gene-based therapies for corneal
      blindness. Recently, researchers have assessed the delivery of therapeutic genes
      for corneal diseases and disorders due to trauma, infections, chemical,
      mechanical, and surgical injury, and/or abnormal wound healing. This review
      provides an update on the developments in gene therapy for corneal diseases and
      discusses the barriers that hinder its utilization for delivering genes in the
      cornea.

PMID- 21967964
TI  - What could possibly go wrong? - A heuristic for predicting population health
      outcomes of interventions.
AB  - Austin Bradford Hill offers a general heuristic for causal inference in
      epidemiology, but no general heuristic for prediction is available. This paper
      seeks to identify a heuristic for predicting the outcome of interventions on
      population health, informed by the moral context of such interventions. It is
      suggested that, where available, robust predictions should be preferred, where a
      robust prediction is one which, according to the best knowledge we are currently
      able to obtain, could not easily be wrong. To assess whether a prediction is
      robust, it is suggested that we ask why the predicted outcome will occur, rather
      than any other outcome. Firstly, if, according to our current knowledge, we
      cannot identify the likeliest ways that the other outcomes could occur, then the
      prediction is not robust. And secondly, if, according to our current knowledge,
      we can identify the likeliest other outcomes but we are unable to say why our
      predicted outcome will occur rather than these, then, again, our prediction is
      not robust. Otherwise, it is robust. The inaccurate but memorable short version
      of the heuristic is, "What could possibly go wrong?"

PMID- 21967965
TI  - [Editorial: Impact factor and the Allergy Mexico Journal].

PMID- 21967966
TI  - [Related systemic reactions to allergen immunotherapy in Monterrey, Mexico].
AB  - BACKGROUND: Patients who receive allergen immunotherapy (IT) have a potential
      risk of systemic reactions, however such reactions are rare when IT administered
      properly. The frequency of systemic reactions (SR) due to conventional IT is less
      than 1%. OBJECTIVE: To determine the frequency of secondary SR to allergen IT,
      and to identify the possible factors involved in developing them. METHODS: A
      retrospective descriptive study that included 2.319 patients who received 14.600
      allergen immunotherapy injections during the period from May 1, 2001 to April 30,
      2002. RESULTS: Twelve patients had a SR (age 7 - 40 years), all of which occurred
      within the first 30 minutes after the IT. These were more frequent during the
      dose - increase phase (58%). The frequency of (RS) in relation to the number of
      injections was 1:1216, and regarding to the number of patients, 1:193. The
      clinical  manifestations included bronchospasm 83%, urticaria 67%,
      gastrointestinal symptoms and hypotension 8.3%. The 58% had anaphylaxis and
      pulmonary or dermatological symptoms only in 33% and 8.3% respectively. The
      possible factors involved in the onset of SR were: sensitivity identified by
      large skin reactions in skin test (PC) 83%, uncontrolled asthma 50%, application
      of allergens IT during high pollination season 42%, inadequate immunotherapy
      scheme monitoring 17%. CONCLUSIONS: The frequency of SR in this group of patients
      was low as that reported in other publications.

PMID- 21967967
TI  - Prevalence of sensitization to inhaled and food allergens in a group of children
      with primary renal tubular acidosis.
AB  - OBJECTIVE: Some reports associate certain illnesses of the urinary system with
      allergies. Thus, we decided to examine the prevalence of sensitization to
      allergens in a group of children with primary renal tubular acidosis (RTA).
      METHODS: Children with primary RTA who attended the nephrology department at a
      third level pediatric hospital during a four-month period, were included. With
      informed parental consent, a questionnaire and skin prick test, total IgE,
      specific IgE and milk precipitins were performed. RESULTS: Forty-three children
      were included, aged 5 months to 9 years (mean, 3.4 +/- 1.8 years), and a
      male/female ratio of 1.7:1. The age of onset of ATR ranged from 2 to 18 months.
      The most common symptoms at the beginning of disease were: failure to thrive and
      lack of appetite. Twenty-one parents (48.8%) noticed an association between the
      introduction of cow's milk and the beginning of symptoms. Skin tests were
      positive in 27.9%. Total IgE levels were elevated in 34.9%, ranged from 5.9 to
      324 IU/mL. Allergen-specific IgE was positive in 25.6%, mainly for milk, wheat
      and egg white. The milk precipitins test was positive in 9 patients (21%).
      CONCLUSIONS: Although this study demonstrated the existence of allergen 
      sensitization in a group of children with RTA, it is necessary to look for this
      association in studies with larger sample size and to use tests with higher
      specificity and sensitivity.

PMID- 21967968
TI  - Transforming growth factor beta and platelets in allergic rhinitis and sinusitis.
AB  - OBJECTIVE: To determine the TGF-? concentration in plasma and platelets in
      patients with allergic rhinitis or rhinosinusitis. METHODS: The study group
      included 36 adult females, 6 with clinical and laboratory diagnoses of allergic
      rhinitis, 18 with allergic rhinitis and sinusitis (rhino-sinusitis) and 12
      clinically healthy controls. The samples were obtained from venous blood. TGF-?
      was measured in plasma and in the supernatant fluid of platelets by a solid phase
      Enzymo-immun assay, and IL-11 was quantified using a commercial enzyme-linked
      immunosorbent assay kit. RESULTS: In both patient groups platelet numbers
      (106/mL) were greater than in controls. Plasma concentration (pg/ml) of TGF-? in
      the allergic rhinitis group (276 +/- 16) was lower than in control group (932 +/-
      99) (p <0.005), whereas in patients with rhino-sinusitis was higher (2606 +/-
      612) (p <0.005). In both patients groups, the intra-platelet TGF-? concentration
      was smaller than in control, but only significant (p <0.005), in allergic
      rhinitis patients. However, in all groups, an inverse correlation (p <0.0001) was
      found between the platelet number and intraplatelet TGF-? levels. CONCLUSIONS:
      The inverse correlation between intra-platelet TGF-? and circulating platelets
      number found in all individuals studied suggests that platelets do not alter the
      regulating mechanism of TGF-? production in allergy or infection.

PMID- 21967969
TI  - [Assessment of nutritional status in children with atopic dermatitis].
AB  - INTRODUCTION: There has been described some exacerbating factors for atopic
      dermatitis, including foods. Several investigations have reported controversial
      results about the influence of foods on atopic dermatitis. But there is scarce
      information about the nutritional status of patients with atopic dermatitis.
      OBJECTIVE: To characterize the nutritional condition in a sample of children with
      atopic dermatitis in Old Havana, Cuba. METHODS: In this descriptive study, were
      included 60 children, aged between 2 and 14 years, with the diagnosis of atopic
      dermatitis from the Allergy Department in the municipality Havana, from January
      to April of 2008. For every patient we evaluated anthropometrics, biochemical and
      immunologic measurements, as well the frequency of meals ingestion and the types
      of foods. RESULTS: We found that 83.3% of the patients were younger than 6 years,
      with a slight prevalence of females (53.3%). Ninety-seven percent of the children
      had a normal height for its age and 48.3% had a normal weight for their height,
      and 20% of the patients had malnutrition. It was detected mild and moderate
      anemia in 63.3%. The daily frequency of taking breakfast was carried out in 55%,
      the lunch in 100% and dinner in 95%. The products of regular consumption are
      carbohydrates, candies nd sodas in 76.6%. Fish and shellfish are consumed only
      for 16% of the patients. CONCLUSIONS: In the studied sample of children with
      atopic dermatitis we found a high prevalence of malnutrition associated with poor
      dietary habits. Breast milk feeding was related to a less malnutrition percentage
      in children with atopic dermatitis.

PMID- 21967970
TI  - The involvement of NF-?B Transcription factor in asthma.
AB  - PubMed search was performed using the key words: NF-?B, nuclear factors, asthma.
      Articles were selected based on their relevance to this review. OBJECTIVE: To
      review the literature regarding the involvement of the nuclear factor kappa-B (NF
      ?B) transcription factor in asthma. RESULTS: NF-?B is a critical transcription
      factor for the production of many inflammatory cytokines. NF-?B is associated
      with several diseases, including asthma, where there is an inflammation of the
      airways with cell infiltration. It is activated in bronchial asthmatic patient
      biopsies and active in the epithelium of the airways in mice after stimulation.
      It also participates in the maintenance of the chronic inflammatory response. NF
      ?B also acts synergistically with other transcription factors, to induce the
      maximal expression of genes involved with asthma. Activation of NF- ?B by several
      stimuli induces the release and degradation of the inhibitory protein I-?B from
      the dimeric complex followed by translocation of NF-?B to the nucleus.
      CONCLUSIONS: The NF-?B pathway is central to the pathogenesis of  asthma. NF?B is
      an important therapeutic target for the treatment of asthma, including
      intermediate products on the signaling pathway and protein related to Rel.
      Alterations in the NF-?B signaling pathway are associated with the disease.

PMID- 21967971
TI  - [Pathophysiology and advances in the treatment of Hereditary Angioedema].
AB  - Hereditary angioedema is an autosomic dominant disease,  caracterized by
      recurrent angioedema and caused by a defective enzime known as C1 inhibitor. The
      main mediator involved in the development of angioedema is bradikynin. There are
      three types of the disease, the first one related to a decrease in the production
      of the enzime, the second one caracterized by an altered function of the enzime
      and the third one due to an altered factor XII gene. The recurrent angioedema may
      be localized in the periphery, in the gastrointestinal system or laryngeal, the
      last one being life  threatening. For its treatment there are a lot of drugs
      available, such as attenuated androgens, fresh frozen plasma, tranexamic acid or
      the enzime substitution by a C1 inhibitor concentrate purified from plasma,
      nanofiltered or recombinant. Recently, treatment has been directed toward the
      avoidance of baradykinin production or its action through its B2 receptor.

PMID- 21967972
TI  - [Chronic granulomatous disease diagnosis: Patients and carriers].
AB  - Chronic granulomatous disease (CGD) is a primary immunodeficiency, it has a
      defect in phagocytosis and its estimated incidence is 1 in 250,000 live births.
      Recurrent infections and granulomas are the most common clinical manifestations.
      CGD is caused by a functional defect in one of the subunits of the NADPH oxidase,
      the patients have mutations in NADPH genes. There are two patterns of
      transmission described in CGD, X-linked and autosomal recessive. The diagnosis of
      CGD is made by direct measurement of superoxide production, ferricytochrome c
      reduction, chemiluminescence, reduction of nitroblue tetrazolium or 1, 2, 3
      dihydrorhodamine oxidation. After the diagnosis of CGD is important to identify
      the pattern of transmission in each case in order to provide genetic counseling
      to the patient's family, as well as inform Xlinked CGD carriers that have a major
      risk to develop autoimmune diseases. The 1, 2, 3, DHR help to identify the
      pattern of transmission and carriers of CGD Xlinked, it is considered as a
      screening method because of its easiness, sensitive and inexpensive cost.

PMID- 21967973
TI  - [Cutaneous mastocytoma: A brief literature review and report of two cases].
AB  - Solitary mastocytoma is an infrecuent benign tumor from a group of cutaneous
      mastocytosis. Common onset in childhood, sometimes congenital. It might be one or
      few lesions on trunk or limbs, with or whithout general symptoms. Its is self
      limited and tends to disappear with time, there is not an effective treatment
      available.

PMID- 21967974
TI  - Quantitative trait mapping reveals a regulatory axis involving peroxisome
      proliferator-activated receptors, PRDM16, transforming growth factor-beta2 and
      FLT3 in hematopoiesis.
AB  - Hematopoiesis is the process whereby BM HSCs renew to maintain their number or to
      differentiate into committed progenitors to generate all blood cells. One
      approach to gain mechanistic insight into this complex process is the
      investigation of quantitative genetic variation in hematopoietic function among
      inbred mouse strains. We previously showed that TGF-beta2 is a genetically
      determined positive regulator of hematopoiesis. In the presence of unknown
      nonprotein serum factors TGF-beta2, but not TGF-beta1 or -beta3, enhances
      progenitor proliferation in vitro, an effect that is subject to mouse strain
      dependent variation mapping to a locus on chr.4, Tb2r1. TGF-beta2-deficient mice
      show hematopoietic defects, demonstrating the physiologic role of this cytokine.
      Here, we show that TGF-beta2 specifically and predominantly cell autonomously
      enhances signaling by FLT3 in vitro and in vivo. A coding polymorphism in Prdm16
      (PR-domain-containing 16) underlies Tb2r1 and differentially regulates
      transcriptional activity of peroxisome proliferator-activated receptor-gamma
      (PPARgamma), identifying lipid PPAR ligands as the serum factors required for
      regulation of FLT3 signaling by TGF-beta2. We furthermore show that PPARgamma
      agonists play a FLT3-dependent role in stress responses of progenitor cells.
      These observations identify a novel regulatory axis that includes PPARs, Prdm16,
      and TGF-beta2 in hematopoiesis.

PMID- 21967975
TI  - Donor-specific anti-HLA Abs and graft failure in matched unrelated donor
      hematopoietic stem cell transplantation.
AB  - Anti-HLA donor-specific Abs (DSAs) have been reported to be associated with graft
      failure in mismatched hematopoietic stem cell transplantation; however, their
      role in the development of graft failure in matched unrelated donor (MUD)
      transplantation remains unclear. We hypothesize that DSAs against a mismatched
      HLA-DPB1 locus is associated with graft failure in this setting. The presence of
      anti-HLA Abs before transplantation was determined prospectively in 592 MUD
      transplantation recipients using mixed-screen beads in a solid-phase fluorescent
      assay. DSA identification was performed using single-Ag beads containing the
      corresponding donor's HLA-mismatched Ags. Anti-HLA Abs were detected in 116
      patients (19.6%), including 20 patients (3.4%) with anti-DPB1 Abs. Overall, graft
      failure occurred in 19 of 592 patients (3.2%), including 16 of 584 (2.7%)
      patients without anti-HLA Abs compared with 3 of 8 (37.5%) patients with DSA (P =
      .0014). In multivariate analysis, DSAs were the only factor highly associated
      with graft failure (P = .0001; odds ratio = 21.3). Anti-HLA allosensitization was
      higher overall in women than in men (30.8% vs 12.1%; P < .0001) and higher in
      women with 1 (P = .008) and 2 or more pregnancies (P = .0003) than in men. We
      conclude that the presence of anti-DPB1 DSAs is associated with graft failure in
      MUD hematopoietic stem cell transplantation.

PMID- 21967976
TI  - Phase 2 trial of clofarabine in combination with etoposide and cyclophosphamide
      in pediatric patients with refractory or relapsed acute lymphoblastic leukemia.
AB  - The outcomes in children with refractory/relapsed (R/R) acute lymphoblastic
      leukemia (ALL) are dismal. The efficacy and safety of intravenous clofarabine 40
      mg/m(2) per day, cyclophosphamide 440 mg/m(2) per day, and etoposide 100 mg/m(2)
      per day for 5 consecutive days in pediatric patients with R/R ALL was evaluated
      in this phase 2 study. The primary endpoint was overall response rate (complete
      remission [CR] plus CR without platelet recovery [CRp]). Among the 25 patients
      (median age, 14 years; pre-B cell ALL, 84%; >= 2 prior regimens: 84%; refractory
      to previous regimen: 60%), the overall response rate was 44% (7 CR, 4 CRp) with a
      67.3-week median duration or remission censored at last follow-up. Most patients
      proceeded to alternative therapy, and 10 patients (40%) received hematopoietic
      stem cell transplantation. Six patients (24%) died because of treatment-related
      adverse events associated with infection, hepatotoxicity, and/or multiorgan
      failure. The study protocol was amended to exclude patients with prior
      hematopoietic stem cell transplantation after 4 of the first 8 patients developed
      severe hepatotoxicity suggestive of veno-occlusive disease. No additional cases
      of veno-occlusive disease occurred. The regimen offered encouraging response
      rates and sustained remission in R/R patients. Future investigation should
      include exploration of patient selection, dosing, and supportive care. This trial
      was registered at www.clinicaltrials.gov as #NCT00315705.

PMID- 21967977
TI  - Targeted delivery of TLR ligands to human and mouse dendritic cells strongly
      enhances adjuvanticity.
AB  - Effective vaccines consist of 2 components: immunodominant antigens and effective
      adjuvants. Whereas it has been demonstrated that targeted delivery of antigens to
      dendritic cells (DCs) improves vaccine efficacy, we report here that co-targeting
      of TLR ligands (TLRLs) to DCs strongly enhances adjuvanticity and immunity. We
      encapsulated ligands for intracellular TLRs within biodegradable nanoparticles
      coated with Abs recognizing DC-specific receptors. Targeted delivery of TLRLs to
      human DCs enhanced the maturation and production of immune stimulatory cytokines
      and the Ag-specific activation of naive CD8(+) T cells. In vivo studies
      demonstrated that nanoparticles carrying Ag induced cytotoxic T-lymphocyte
      responses at 100-fold lower adjuvant dose when TLRLs were co-encapsulated instead
      of administered in soluble form. Moreover, the efficacy of these targeted TLRLs
      reduced the serum cytokine storm and related toxicity that is associated with
      administration of soluble TLRLs. We conclude that the targeted delivery of
      adjuvants may improve the efficacy and safety of DC-based vaccines.

PMID- 21967978
TI  - Presence of FLT3-ITD and high BAALC expression are independent prognostic markers
      in childhood acute myeloid leukemia.
AB  - Mutation status of FLT3, NPM1, CEBPA, and WT1 genes and gene expression levels of
      ERG, MN1, BAALC, FLT3, and WT1 have been identified as possible prognostic
      markers in acute myeloid leukemia (AML). We have performed a thorough prognostic
      evaluation of these genetic markers in patients with pediatric AML enrolled in
      the Nordic Society of Pediatric Hematology and Oncology (NOPHO) 1993 or NOPHO
      2004 protocols. Mutation status and expression levels were analyzed in 185 and
      149 patients, respectively. Presence of FLT3-internal tandem duplication (ITD)
      was associated with significantly inferior event-free survival (EFS), whereas
      presence of an NPM1 mutation in the absence of FLT3-ITD correlated with
      significantly improved EFS. Furthermore, high levels of ERG and BAALC transcripts
      were associated with inferior EFS. No significant correlation with survival was
      seen for mutations in CEBPA and WT1 or with gene expression levels of MN1, FLT3,
      and WT1. In multivariate analysis, the presence of FLT3-ITD and high BAALC
      expression were identified as independent prognostic markers of inferior EFS. We
      conclude that analysis of the mutational status of FLT3 and NPM1 at diagnosis is
      important for prognostic stratification of patients with pediatric AML and that
      determination of the BAALC gene expression level can add valuable information.

PMID- 21967979
TI  - Tyrosine phosphorylated c-Cbl regulates platelet functional responses mediated by
      outside-in signaling.
AB  - c-Cbl protein functions as an E3 ligase and scaffolding protein, where 3
      residues, Y700, Y731, and Y774, upon phosphorylation, have been shown to initiate
      several signaling cascades. In this study, we investigated the role of these
      phospho-tyrosine residues in the platelet functional responses after integrin
      engagement. We observed that c-Cbl Y700, Y731 and Y774 undergo phosphorylation
      upon platelet adhesion to immobilized fibrinogen, which was inhibited in the
      presence of PP2, a pan-src family kinase (SFK) inhibitor, suggesting that c-Cbl
      is phosphorylated downstream of SFKs. However, OXSI-2, a Syk inhibitor,
      significantly reduced c-Cbl phosphorylation at residues Y774 and Y700, without
      affecting Y731 phosphorylation. Interestingly, PP2 inhibited both platelet
      spreading on fibrinogen as well as clot retraction, whereas OXSI-2 blocked only
      platelet-spreading, suggesting a differential role of these tyrosine residues.
      The physiologic role of c-Cbl and Y731 was studied using platelets from c-Cbl KO
      and c-Cbl(YF/YF) knock-in mice. c-Cbl KO and c-Cbl(YF/YF) platelets had a
      significantly reduced spreading over immobilized fibrinogen. Furthermore, clot
      retraction with c-Cbl KO and c-Cbl(YF/YF) platelets was drastically delayed.
      These results indicate that c-Cbl and particularly its phosphorylated residue
      Y731 plays an important role in platelet outside-in signaling contributing to
      platelet-spreading and clot retraction.

PMID- 21967981
TI  - Case report: The management of advanced oral cancer in a Jehovah's Witness using
      the Ultracision Harmonic Scalpel.
AB  - We present the first case of a head and neck oncological procedure accomplished
      in a Jehovah's Witness using the Ultracision Harmonic Scalpel (Ethicon,
      Cincinnati, OH). Jehovah's Witnesses present a serious challenge to the head and
      neck cancer surgeon due to their refusal to accept transfusion of any blood
      products. However, our experience reinforces the view that surgical management of
      head and neck cancer is possible in these patients. We show the Harmonic Scalpel,
      an ultrasonic tissue dissector, to be a useful surgical tool in obviating the
      need for blood transfusion. Preoperative optimisation, intra-operative surgical
      and anaesthetic techniques are also fully discussed.

PMID- 21967982
TI  - Modulation of fibril formation by a beta-sheet breaker peptide ligand: an
      electrochemical approach.
AB  - The development of generic inhibitors in order to control the formation of
      amyloid fibrils and early oligomers is still an unmet medical need. Here, we
      demonstrate the applicability of electrochemical analysis for the detection of
      beta-sheet breaker peptide ligands that act as excellent inhibitors of
      Alzheimer's disease (AD) amyloid-beta (Abeta) fibrils and oligomers in vitro. As
      the case study, a well-defined beta-sheet breaker pentapeptide (LPFFD, FibIII)
      was utilized with Abeta(1-42) peptides. Square wave voltammetry (SWV)
      measurements were confirmed with simultaneous fluorescence analysis of the same
      incubated Abeta samples using a well-known fluorescent marker of beta-sheet
      formation, Thioflavin T (ThT). Significant changes in the electrochemical signals
      were observed for the interaction of the Abeta oligomers with FibIII at the early
      stages of aggregation. The electrochemical approach, in principle, allowed
      monitoring beta-sheet breaker-Abeta interactions on the time scale of aggregation
      in a label-free and cost-effective format using screen-printed carbon strip
      (SPCS) electrodes.

PMID- 21967980
TI  - Delta12-prostaglandin J3, an omega-3 fatty acid-derived metabolite, selectively
      ablates leukemia stem cells in mice.
AB  - Targeting cancer stem cells is of paramount importance in successfully preventing
      cancer relapse. Recently, in silico screening of public gene-expression datasets
      identified cyclooxygenase-derived cyclopentenone prostaglandins (CyPGs) as likely
      agents to target malignant stem cells. We show here that Delta(12)-PGJ(3), a
      novel and naturally produced CyPG from the dietary fish-oil omega-3
      polyunsaturated fatty acid eicosapentaenoic acid (EPA; 20:5) alleviates the
      development of leukemia in 2 well-studied murine models of leukemia. IP
      administration of Delta(12)-PGJ(3) to mice infected with Friend erythroleukemia
      virus or those expressing the chronic myelogenous leukemia oncoprotein BCR-ABL in
      the hematopoietic stem cell pool completely restored normal hematologic
      parameters, splenic histology, and enhanced survival. More importantly, Delta(12)
      PGJ(3) selectively targeted leukemia stem cells (LSCs) for apoptosis in the
      spleen and BM. This treatment completely eradicated LSCs in vivo, as demonstrated
      by the inability of donor cells from treated mice to cause leukemia in secondary
      transplantations. Given the potency of omega-3 polyunsaturated fatty acid-derived
      CyPGs and the well-known refractoriness of LSCs to currently used clinical
      agents, Delta(12)-PGJ(3) may represent a new chemotherapeutic for leukemia that
      targets LSCs.

PMID- 21967983
TI  - The HIV/AIDS epidemic in sub-Saharan Africa: thinking ahead on programmatic tasks
      and related operational research.
AB  - Until now, we have all been desperately trying to run behind the HIV/AIDS
      epidemic and catch up with it, but despite all our efforts, the epidemic remains
      well ahead of us. In 2010, the antiretroviral treatment (ART) gap was about 60%,
      AIDS-related deaths were almost two million a year, and on top of these figures,
      for every one person started on ART, there were two new HIV infections. What is
      needed to change this situation is to think ahead of the epidemic in terms of the
      programmatic tasks we will be faced with and try to act boldly in trying to
      implement those tasks. From a programmatic perspective, we: a) highlight what
      needs to fundamentally change in our thinking and overall approach to the
      epidemic; and b) outline a number of key task areas for implementation and
      related operational research.

PMID- 21967984
TI  - Is brain-derived neurotrophic factor a selective biomarker that predicts cocaine
      relapse outcomes?

PMID- 21967985
TI  - Manipulation of cigarette craving with transcranial magnetic stimulation.

PMID- 21967986
TI  - Understanding the neural circuitry of appetitive regulation in eating disorders.

PMID- 21967987
TI  - Response perseveration in stimulant dependence is associated with striatal
      dysfunction and can be ameliorated by a D(2/3) receptor agonist.
AB  - BACKGROUND: Compulsivity is a hallmark of drug addiction and in animal models is
      measured by consecutive incorrect responses to a previously rewarded stimulus
      during reversal learning. The aim of this study was to measure behavioral and
      neural markers of compulsivity in stimulant-dependent individuals and to test
      whether these markers could be modulated by treatment with drugs targeting the
      dopamine system. METHODS: In a randomized, double-blind, placebo-controlled,
      crossover design, stimulant-dependent individuals (SDIs; n = 18) and healthy
      volunteers (n = 18) received single doses of dopamine D(2/3) receptor antagonist
      (amisulpride, 400 mg) and agonist (pramipexole, 0.5 mg) drugs. To examine
      compulsivity and its dopaminergic modulation more generally, patients with
      obsessive-compulsive disorder (OCD; n = 18) were also included in the study.
      RESULTS: SDIs made significantly more perseverative responses to the previously
      correct stimulus immediately following reversal, compared with both healthy
      volunteers and patients with OCD. Across all participants, the number of
      perseverative errors was negatively correlated with functional activation in
      right fronto-striato-parietal networks-in particular, the right caudate nucleus.
      In SDIs, perseveration-related caudate activation was abnormally reduced in the
      placebo condition, but the dopamine D(2/3) agonist pramipexole normalized both
      perseverative responding and related activation of the right caudate.
      CONCLUSIONS: Perseveration during reversal learning was associated specifically
      with stimulant dependence rather than with compulsive behaviors more generally.
      The beneficial effects of a dopamine agonist drug challenge on both behavior and
      associated brain activation in SDIs may indicate new avenues for pharmacologic
      treatment in stimulant dependence.

PMID- 21967989
TI  - Construction and demolition waste as a source of PVC for recycling.
AB  - Construction and demolition waste can contain considerable amounts of polyvinyl
      chloride (PVC). This paper describes a study of the recycling of PVC pipes
      collected from such waste materials. In a sorting facility for the specific
      disposal of construction and demolition waste, PVC was found to represent one
      third of the plastics separated by workers. Pipes were sorted carefully to
      preclude any possible contamination by poly(ethylene terephthalate) (PET) found
      in the waste. The material was ground into two distinct particle sizes (final
      mesh of 12.7 and 8 mm), washed, dried and recycled. The average formulation of
      the pipes was determined based on ash content tests and used in the fabrication
      of a similar compound made mainly of virgin PVC. Samples of recycled pipes and of
      compound based on virgin material were subjected to tensile and impact tests and
      provided very similar results. These results are a good indication of the
      application potential of the recycled material and of the fact that longer
      grinding to obtain finer particles is not necessarily beneficial.

PMID- 21967988
TI  - Congenital hyperinsulinism: current trends in diagnosis and therapy.
AB  - Congenital hyperinsulinism (HI) is an inappropriate insulin secretion by the
      pancreatic beta-cells secondary to various genetic disorders. The incidence is
      estimated at 1/50, 000 live births, but it may be as high as 1/2, 500 in
      countries with substantial consanguinity. Recurrent episodes of hyperinsulinemic
      hypoglycemia may expose to high risk of brain damage. Hypoglycemias are diagnosed
      because of seizures, a faint, or any other neurological symptom, in the neonatal
      period or later, usually within the first two years of life. After the neonatal
      period, the patient can present the typical clinical features of a hypoglycemia:
      pallor, sweat and tachycardia. HI is a heterogeneous disorder with two main
      clinically indistinguishable histopathological lesions: diffuse and focal.
      Atypical lesions are under characterization. Recessive ABCC8 mutations (encoding
      SUR1, subunit of a potassium channel) and, more rarely, recessive KCNJ11
      (encoding Kir6.2, subunit of the same potassium channel) mutations, are
      responsible for most severe diazoxide-unresponsive HI. Focal HI, also diazoxide
      unresponsive, is due to the combination of a paternally-inherited ABCC8 or KCNJ11
      mutation and a paternal isodisomy of the 11p15 region, which is specific to the
      islets cells within the focal lesion. Genetics and 18F-fluoro-L-DOPA positron
      emission tomography (PET) help to diagnose diffuse or focal forms of HI.
      Hypoglycemias must be rapidly and intensively treated to prevent severe and
      irreversible brain damage. This includes a glucose load and/or a glucagon
      injection, at the time of hypoglycemia, to correct it. Then a treatment to
      prevent the recurrence of hypoglycemia must be set, which may include frequent
      and glucose-enriched feeding, diazoxide and octreotide. When medical and dietary
      therapies are ineffective, or when a focal HI is suspected, surgical treatment is
      required. Focal HI may be definitively cured when the partial pancreatectomy
      removes the whole lesion. By contrast, the long-term outcome of diffuse HI after
      subtotal pancreatectomy is characterized by a high risk of diabetes, but the time
      of its onset is hardly predictable.

PMID- 21967990
TI  - Impact of factor VIII and von Willebrand factor plasma levels on cerebral venous
      and sinus thrombosis: are they independent risk factors?
AB  - BACKGROUND: The aim of this study was to assess the plasma levels of factor VIII
      (FVIII), von Willebrand factor (vWF) and their association in patients with
      cerebral venous sinus thrombosis (CVST). METHODS: We prospectively included 25
      CVST patients admitted to the university hospital and 53 voluntary subjects as a
      control group. FVIII and vWF were measured after 6 months when anticoagulant
      therapy was stopped. RESULTS: The mean FVIII and vWF levels were significantly
      higher in the CVST group compared to the control group (126.21 +/- 54.69 vs. 91.9
      +/- 48.8 IU/dl; p = 0. 012; 157.05 +/- 107.74 vs. 94 +/- 84%; p = 0.01,
      respectively). Using analyses calculating the 95th percentile cut-off values, we
      found high levels of FVIII in patients compared to controls (29.2 vs. 5%; p =
      0.01) and the odds ratio with 95% confidence interval (CI) was 7.82 (1.46, 41.6).
      After adjustment for vWF levels, sex and age, the risk remained significantly
      increased and the odds ratio with 95% CI was 10.5 (1.1, 101.4) (p = 0.041).
      CONCLUSION: FVIII is one of the most prevalent risk factors of CVST and may be
      associated with an approximately tenfold increased risk for developing CVST. This
      effect is independent of vWF levels; however, vWF is not an independent risk
      factor of CVST.

PMID- 21967991
TI  - Results of a BoNT/A antibody study in children and adolescents after
      onabotulinumtoxin A (Botox(r)) detrusor injection.
AB  - BACKGROUND: Onabotulinumtoxin A (OnaBoNT/A, Botox(r)) is effective in the
      treatment of neurogenic detrusor overactivity, however this therapy can fail. In
      a prospective study, we analyzed patient serum for BoNT/A antibodies (BoNT/A-AB)
      as a possible cause of therapy failure. METHODS: 17 patients (average age 14.5
      years) who had neurogenic detrusor overactivity were admitted for repeated
      OnaBoNT/A injection into the detrusor muscle. We analyzed their serum for BoNT/A
      AB. The clinical findings were correlated with the incidence of BoNT/A-AB.
      RESULTS: Positive BoNT/A-AB were clearly or marginally determined in 6 patients.
      Therapy had failed in all 6. In 4 of the 6, therapy might have failed because of
      a low-compliance bladder (3 patients) or tethered-cord syndrome (1), but BoNT/A
      AB were found as the only possible cause in 2 patients. Thus, the incidence of
      BoNT/A-AB in the 17 patients was 35%, and the antibodies were clinically
      significant in 12%. All patients with BoNT/A-AB had a history of recurrent
      urinary tract infections. CONCLUSIONS: Patients who show a failure of therapy
      after OnaBoNT/A injections for which no other causes can be determined should
      have their serum checked for BoNT/A-AB. Recurrent urinary tract infection might
      be a predisposing factor for BoNT/A-AB.

PMID- 21967992
TI  - In vitro degradation and drug-release properties of water-soluble chitosan cross
      linked oxidized sodium alginate core-shell microgels.
AB  - Hydrogels based on sodium alginate (SA) have already been widely used in
      biomedical applications using Ca(2+) as a cross-linker; however, these hydrogels
      tend to disintegrate in electrolyte solutions. To solve this problem, we present
      a kind of oxidized sodium alginate (OSA) microgel using water-soluble chitosan
      (WSC) as a cross-linker. This microgel was successfully prepared via an emulsion
      cross-linking technique at room temperature. The microgel was cross-linked by the
      formation of both Schiff base bonds and inter-polyelectrolyte complexes, which
      can efficiently eliminate the disintegration of the microgel in electrolyte
      solutions. Morphological properties of the resulting microgels were determined by
      transmission electron microscopy (TEM), hydrodynamic diameters of the microgels
      were characterized by dynamic light scattering (DLS). The objective of this work
      was to achieve the colon-specific delivery of an anti-ulcerative colitis drug. 5
      Aminosalicylic acid (5-ASA) was chosen as a model drug and the in vitro drug
      release profile was established in buffer solutions with 0.1 M HCl/NaCl (pH 1.2)
      and 0.1 M phosphate-buffered saline (PBS, pH 7.4) at 37 degrees C. The microgel
      was incubated in 0.1 M PBS (pH 7.4) at 37 degrees C to determine its degradation
      behavior. Cell cytotoxicity (tested by MTT assay) showed that this microgel had
      no significant cytotoxicity. These results indicated that this microgel prepared
      by introducing WSC into OSA may have potential applications in oral controlled
      drug-delivery systems. Therefore, the OSA/WSC microgel may be a useful carrier
      for the colon-specific delivery of anti-inflammatory drugs including 5-ASA and
      the enhanced therapeutic effect of ulcerative colitis. 

PMID- 21967993
TI  - Epicardial fat: from the biomolecular aspects to the clinical practice.
AB  - Epicardial fat is the visceral fat depot of heart. It is a metabolically active
      organ with anatomical and functional contiguity to the myocardium. A dichotomous
      role has been attributed to the epicardial fat. Under physiological conditions,
      epicardial fat displays biochemical and thermogenic cardio-protective properties.
      Under pathological circumstances epicardial fat can locally affect the heart and
      coronary arteries through vasocrine or paracrine secretion of pro-inflammatory
      cytokines. Epicardial fat can be measured with imaging techniques. Epicardial fat
      thickness reflects intra-abdominal and myocardial fat and correlates with
      metabolic syndrome and coronary artery disease. Epicardial fat measurement may
      play a role in the stratification of the cardio-metabolic risk and serve as
      therapeutic target. Weight loss and anti-inflammatory drugs targeting the fat may
      modulate epicardial fat. Because epicardial and myocardial tissues share the same
      coronary arterial supply it is reasonable to hypothesize that improved local
      vascularisation may resume epicardial fat to its physiological role.

PMID- 21967994
TI  - Selenium, iodine, and the relation with Kashin-Beck disease.
AB  - The etiology and pathogenesis of Kashin-Beck disease (KBD) remain uncertain at
      present. A deficiency of selenium and iodine is considered common in KBD-affected
      areas. Supplying selenium and iodine for the prevention of KBD has been performed
      in the past few decades in affected areas in China. Supplying selenium and/or
      iodine has produced positive http://www.iciba.com/different/effects in most KBD
      affected areas, but there are some affected areas where the effects have been
      unclear and supplementation with selenium and/or iodine has not eliminated this
      disease. From animal and vitro experiments, we explore whether a deficiency of
      selenium and/or iodine may be the environmental factor causing KBD. KBD may have
      multiple etiologies. The role of selenium and iodine in KBD mainly involves
      antioxidation and maintenance of thyroid function according to the present
      review. Other important roles of selenium and iodine in KBD and a certain
      etiology of this disease need further study.

PMID- 21967995
TI  - Late onset malnutrition from esophageal and phrenic dysfunction after
      radiotherapy for Hodgkin's lymphoma: a case report.
AB  - Radiotherapy may lead to late-onset, rare, but sometimes life-threatening
      complications that need to be recognized for timely management. We report the
      case of a 39-year-old man who presented with a 20-kg weight loss with severe
      dysphagia and respiratory failure. His medical history was noticeable for
      Hodgkin's lymphoma that was treated 20 y previously. The physical examination and
      electroneuromyography indicated vagal and phrenic neuropathies. We concluded that
      the patient had late-onset esophageal motor disorder and bilateral phrenic
      paralysis secondary to the radiotherapy received 20 y previously for the
      lymphoma. The patient's management included long-term nutritional support.
      Although late-onset vagal and phrenic nerve injuries have been described
      separately after radiotherapy, we report the first case of paralysis at both
      sites. Another striking feature of this observation is the subsequent severe
      malnutrition that accompanied these paralyses.

PMID- 21967996
TI  - Association between MTHFR C677T genotype and circulating folate levels
      irrespective of folate intake: data from the IMMIDIET Project.

PMID- 21967997
TI  - Experience with telehealth for sleep monitoring and sleep laboratory management.
AB  - In 2009, we established a pilot telehealth service to a sleep laboratory in
      Garden City, Kansas, approximately 600 km from the Kansas University Medical
      Center. Videoconferencing was used for polysomnography (PSG) study follow-up,
      patient monitoring and sleep laboratory medical management. It allowed the sleep
      specialist to treat patients and collaborate with sleep laboratory personnel from
      a distance without extensive travel. In the first six months the telemedicine
      clinic was held on six occasions. There were 18 new patient evaluations and four
      follow up visits. The most common diagnosis was obstructive sleep apnoea. The
      videoconferencing equipment and the intraoral camera worked well. Interviewing
      and examining patients via telemedicine was very similar to doing it in-person.
      Telemedicine was effective for the physician-patient interaction and for
      visualizing airway structures. Although more research is needed, the use of
      videoconferencing for sleep study follow-up and laboratory oversight appears very
      promising.

PMID- 21967998
TI  - Impact of a kiosk educational module on HIV screening rates and patient
      knowledge.
AB  - We assessed the effect of a kiosk educational module on HIV screening rates and
      patient knowledge about HIV testing. The evaluation was performed in a walk-in
      clinic offering routine HIV screening. During alternating two-week periods,
      patients were referred either to view a kiosk-based, educational module prior to
      receiving usual care, or the kiosk module was turned off and no alterations to
      care processes were made. The primary outcome was HIV testing rate. The secondary
      outcome was knowledge about HIV rapid screening, as measured with a
      questionnaire. There were 71 patients in the kiosk periods and 79 patients in the
      usual-care periods. The overall HIV testing rate was 41%. The kiosk period was
      not associated with greater odds of HIV testing (OR 0.7; 95% CI: 0.4-1.4). In 44
      patients who completed the knowledge survey, the kiosk group was strongly
      associated with increased knowledge (predicted increase in knowledge score: 1.3;
      95% CI: 036-2.1). The brief kiosk educational module did not improve HIV
      screening rates, but it increased overall patient knowledge about HIV testing.

PMID- 21967999
TI  - The utility of providing automated medication dose reminders to young children on
      chronic medication.
AB  - We investigated the effect of text message reminders about medication
      administration. The study concerned children with cystic fibrosis. We provided 20
      children (aged 5-12 years) with pagers that they could customize. For the first
      two weeks, we sent friendly text messages (non-reminder content) near medication
      times to acquaint them with the use of the pager. For the second two weeks, we
      sent messages reminding children to take their medications. The parents completed
      a survey to assess the child's overall use of the pager and degree of
      participation in medication management. Sixteen out of 20 children completed the
      study. Of these, 14 children (88%) were able to help notify parents when
      medications were due. Children as young as seven years of age may be able to
      receive reminders about medication administration events. The pilot study
      demonstrated the feasibility of involving younger children in pager technology
      related to medication adherence.

PMID- 21968000
TI  - A telemedicine network to support paediatric care in small hospitals in rural
      Tanzania.
AB  - We reviewed our experience with the Tanzanian Telemedicine Network in supporting
      paediatric care at 40 small, rural hospitals in the country. The network began
      operating in 2008. Store and forward telemedicine was provided via the open
      source software iPath. The 33 volunteer consultants were based in several
      countries, although most of them had practical experience in Tanzania. During the
      first three years of network operation there were 533 referrals. There were 159
      paediatric cases (median age five years). Three paediatric specialists provided
      most consultations (64%), but other specialists provided recommendations when
      required. The response time was usually less than two days (median 6 h; inter
      quartile range 2-24 h). A precise recommendation was not always provided, but
      since all consultants had an intimate knowledge of the state of health services
      in Tanzania, their advice was usually well adapted to the local circumstances of
      the hospitals. Referral to a higher level of care was recommended in 26 cases
      (16%). A simple web-based telemedicine system combined with email alerts is
      feasible in remote locations in Tanzania, even where fast Internet connections
      are not available.

PMID- 21968001
TI  - Teledermatology in pharmacies: a pilot study.
AB  - We investigated community pharmacists' management of skin conditions in order to
      identify a need for further educational support. Twenty community pharmacists in
      Queensland completed a questionnaire regarding their management of skin
      conditions and their opinions regarding the usefulness of a potential
      teledermatology service. The pharmacists' accuracy in managing skin conditions
      was tested by a dermatologist who reviewed the pharmacists' advice in 33 cases
      obtained by 14 pharmacists. Overall agreement between the pharmacists and the
      dermatologist was moderate, with a kappa statistic of 0.58 (P < 0.05) The uptake
      of a potential teledermatology service was investigated in one pharmacy over one
      month. Five patients were offered the teledermatology service. Of these, two
      patients consented and three refused. All pharmacists (n = 20) indicated a desire
      for further education and supported the idea of a teledermatology service.

PMID- 21968003
TI  - Temporal locations of repolarization alternans within the electrocardiogram JT
      interval in patients with acute myocardial infarction and healthy subjects.

PMID- 21968002
TI  - The intracellular trafficking pathway of transferrin.
AB  - BACKGROUND: Transferrin (Tf) is an iron-binding protein that facilitates iron
      uptake in cells. Iron-loaded Tf first binds to the Tf receptor (TfR) and enters
      the cell through clathrin-mediated endocytosis. Inside the cell, Tf is trafficked
      to early endosomes, delivers iron, and then is subsequently directed to recycling
      endosomes to be taken back to the cell surface. SCOPE OF REVIEW: We aim to review
      the various methods and techniques that researchers have employed for elucidating
      the Tf trafficking pathway and the cell-machinery components involved. These
      experimental methods can be categorized as microscopy, radioactivity, and surface
      plasmon resonance (SPR). MAJOR CONCLUSIONS: Qualitative experiments, such as
      total internal reflectance fluorescence (TIRF), electron, laser-scanning
      confocal, and spinning-disk confocal microscopy, have been utilized to determine
      the roles of key components in the Tf trafficking pathway. These techniques allow
      temporal resolution and are useful for imaging Tf endocytosis and recycling,
      which occur on the order of seconds to minutes. Additionally, radiolabeling and
      SPR methods, when combined with mathematical modeling, have enabled researchers
      to estimate quantitative kinetic parameters and equilibrium constants associated
      with Tf binding and trafficking. GENERAL SIGNIFICANCE: Both qualitative and
      quantitative data can be used to analyze the Tf trafficking pathway. The valuable
      information that is obtained about the Tf trafficking pathway can then be
      combined with mathematical models to identify design criteria to improve the
      ability of Tf to deliver anticancer drugs. This article is part of a Special
      Issue entitled Transferrins: Molecular mechanisms of iron transport and
      disorders.

PMID- 21968004
TI  - Equivalence of mean intercept length and gradient fabric tensors - 3D study.
AB  - In this study the relationship between the mean intercept length (MIL) method -
      the current standard histomorphometric method of assessing structural anisotropy
      and an alternative method of the gray-level structure tensor (GST) is
      investigated. Both methods are applied to a set of 25 three-dimensional binary
      MUCT images of trabecular bone. It is shown that there is a very strong
      correlation between the logarithms of the principal values of the MIL and the GST
      fabric tensors (Pearson's coefficient of correlation higher than 0.98) and
      between the logarithms of the invariants of the MIL and the GST fabric tensors
      (Pearson's coefficient of correlation higher than 0.999). There is also a good
      correlation between the degree of anisotropy calculated from the MIL and from the
      GST tensors (Pearson's coefficient of correlation equal to 0.90). The principal
      anisotropy directions of the MIL and the GST fabric tensors coincide at the 5%
      significance level. Additionally, the performance of both methods is tested,
      based on a set of artificial structures with prescribed orientations.

PMID- 21968005
TI  - Accelerometry is associated with walking mobility, not physical activity, in
      persons with multiple sclerosis.
AB  - Accelerometers are seemingly a criterion standard of real-life walking mobility
      and this is supported by assumptions and empirical data. This application would
      be strengthened by including objective measures of walking mobility along with a
      matched control sample for verifying specificity versus generality in
      accelerometer output. We compared associations among accelerometer output,
      walking mobility, and physical activity between persons with multiple sclerosis
      (MS) and controls without a neurological disorder. Sixty-six persons (33 MS, 33
      matched controls) completed a battery of questionnaires, performed the six-minute
      walk (6MW) and timed-up-and-go (TUG), and wore an accelerometer for a 7-day
      period. After this period, participants completed the Godin Leisure-Time Exercise
      Questionnaire (GLTEQ) and International Physical Activity Questionnaire (IPAQ).
      Accelerometer output was significantly correlated with only mobility measures
      (6MW, rho=.78; TUG, rho=-.68) in MS, whereas it correlated with both mobility
      (6MW, rho=.58; TUG, rho=-.49) and physical activity (GLTEQ, rho=.56; IPAQ,
      rho=.53) measures in controls. Regression analysis indicated that only 6MW
      explained variance in accelerometer output in MS (beta=.65, R(2)=.43). These
      findings support the possibility that accelerometers primarily and specifically
      measure real-life walking mobility, not physical activity, in persons with MS.

PMID- 21968006
TI  - Eczematous dermatitis caused by tetrazepam.

PMID- 21968008
TI  - Changes in 10-12 year old's fruit and vegetable intake in Norway from 2001 to
      2008 in relation to gender and socioeconomic status - a comparison of two cross
      sectional groups.
AB  - BACKGROUND: Norwegian children and adolescents eat less than half of the
      recommended 5 portions of fruit and vegetables (FV) per day. Gender and
      socioeconomic disparities in FV consumption shows that boys and children of lower
      socioeconomic status (SES) eat less FV than girls and high SES children. We also
      know that accessibility and preferences has been identified as two important
      determinants of FV intake. The objectives of this study were to compare FV intake
      among Norwegian 6th and 7th graders in 2001 and 2008, to explore potential
      mediated effects of accessibility and preferences on changes in FV over time, to
      explore whether these changes in FV intake was moderated by gender and/or SES and
      whether a moderated effect in FV intake was mediated by accessibility and
      preferences of FV. METHODS: The baseline survey of the Fruits and Vegetables Make
      the Marks project was conducted in 2001 at 38 randomly chosen schools in two
      Norwegian counties. A second survey was conducted at the same schools in 2008. A
      total of 27 schools participated in both surveys (2001 n = 1488, 2008 n = 1339).
      FV intake was measured by four food frequency questions (times/week) in a
      questionnaire which the pupils completed at school. SES was based on parents'
      reports of their own educational level in a separate questionnaire. The main
      analyses were multilevel linear regression analyses. RESULTS: A significant
      year*parental educational level interaction was observed (p = 0.01). FV intake
      decreased among pupils of parents with lower educational level (13.9 vs. 12.6
      times/week in 2001 and 2008, respectively), but increased among pupils of parents
      with higher education (14.8 vs. 15.0 times/week, respectively). This increasing
      SES disparity in FV intake was partly mediated by an increasing SES disparity in
      accessibility and preferences over time, wherein children with higher educated
      parents had a steeper increase in accessibility and preferences over time than
      children with lower educated parents. The year*sex interaction was not
      significant (p = 0.54). CONCLUSIONS: This study shows an increase in SES
      disparities in 6th and 7th graders FV intake from 2001 to 2008, partly mediated
      by an increasing SES disparity in accessibility and preferences of FV.

PMID- 21968007
TI  - Triggers of asthma and COPD: are they different?
AB  - BACKGROUND: Asthma symptoms can be triggered by a variety of factors commonly
      referred to as "triggers". Some of these factors can also induce severe asthma
      exacerbations. Thus, it can be assumed that actions taken against such triggers
      may prevent the progression of the disease. However, limited data exist on the
      clinical importance of these triggers in patients with chronic obstructive
      pulmonary disease (COPD). OBJECTIVE: To compare the effect of triggers on
      symptoms and actions taken against certain modifiable triggers in patients with
      asthma and COPD. METHODS: The study was conducted in a university hospital
      between June 2009 and June 2010. Patients with asthma and COPD were asked to
      complete a questionnaire in which both the factors triggering symptoms and the
      actions taken against several triggers were assessed. RESULTS: Three hundred
      consecutive adult patients (150 asthma, 150 COPD) were enrolled to the study. The
      frequency of triggering factors was similar in both groups. Vaccination rates for
      influenza and pneumococcus were significantly higher in patients with COPD.
      However, such anti-allergic approaches as the use of strategies to decrease dust
      exposure, the use of anti-mite bed sheets, and the removal of pets from the home
      were more commonly employed by asthmatic patients. CONCLUSION: This study
      revealed that certain triggers affected COPD and asthma patients to the same
      degree. Therefore, triggers and strategies for controlling modifiable triggers
      should be more concentrated on during education in both groups. However, the
      preventive effect of these strategies on disease progression, particularly in
      patients with COPD, needs clarification.

PMID- 21968009
TI  - Chitosan scaffolds containing silicon dioxide and zirconia nano particles for
      bone tissue engineering.
AB  - A scaffold harboring the desired features such as biodegradation,
      biocompatibility, porous structure could serve as template for bone tissue
      engineering. In the present study, chitosan (CS), nano-scaled silicon dioxide
      (Si) and zirconia (Zr) were combined by freeze drying technique to fabricate a
      bio-composite scaffold. The bio-composite scaffold (CS/Si/Zr) was characterized
      by SEM, XRD and FT-IR studies. The scaffold possessed a porous nature with pore
      dimensions suitable for cell infiltration and colonization. The presence of
      zirconia in the CS/Si/Zr scaffold decreased swelling and increased
      biodegradation, protein adsorption and bio-mineralization properties. The
      CS/Si/Zr scaffold was also found to be non-toxic to rat osteoprogenitor cells.
      Thus, we suggest that CS/Si/Zr bio-composite scaffold is a potential candidate to
      be used for bone tissue engineering.

PMID- 21968010
TI  - A novel glycosaminoglycan-like polysaccharide from abalone Haliotis discus hannai
      Ino: purification, structure identification and anticoagulant activity.
AB  - A novel glycosaminoglycan-like sulfated polysaccharide (AAP) from the pleopods of
      Haliotis discus hannai Ino was purified by DEAE ion exchange chromatography
      followed with S-300 HR geltrion chromatography. Chemical composition analysis
      indicated that AAP was composed of galactosamine, glucuronic acid, fucose,
      galactose with a ratio of 2.14:2.37:2.94:1, the content of sulfate was 15.5%. The
      average molecular weight (M(w)) was 56.2 kDa in a TSK G4000 column. Further IR,
      1D, 2D NMR spectroscopic analysis of the correlation signals of different sugar
      units gave a proposal repeating structure, as follows: [chemical structure: see
      the text] In vitro anticoagulant assay indicated AAP prolonged both the activated
      partial thromboplastin time (APTT) and thrombin time (TT), with a 22.5 U/mg and
      72.0 U/mg compared with standard heparin, respectively. The anticoagulant
      property of AAP was mainly attributed to powerful potentiation thrombin by anti
      thrombin III.

PMID- 21968011
TI  - Effects of icodextrin on patient survival and technique success in patients
      undergoing peritoneal dialysis.
AB  - BACKGROUND: Many studies have suggested clinical benefits of icodextrin in
      peritoneal dialysis (PD) patients regarding fluid management, glycaemic control
      and metabolic improvement. However, reports on whether icodextrin can improve
      patient and technique survival is sparse. METHODS: A total of 2163 patients from
      54 centres in Korea who initiated PD from July 2003 to December 2006 were
      enrolled. Outcomes data were retrieved retrospectively from the Baxter Korea
      database. Among these patients, 641 patients who had been prescribed icodextrin
      for >50% of their PD duration were defined as the 'icodextrin' group and the
      remaining 1522 patients as the 'non-icodextrin' group. Propensity score matching
      yielded 640 matched pairs of patients. We compared all-cause mortality and
      technique failure rates between the two groups. RESULTS: There were no
      significant differences in age, gender, diabetes, cardiovascular comorbidity,
      socioeconomic status, biocompatible solution use in short dwells or centre
      experience between the two groups. Death occurred in 92 (14.4%) patients in the
      icodextrin group compared with 128 (20.0%) in the non-icodextrin group [hazard
      ratio (HR), 0.69; 95% confidence interval (CI), 0.53-0.90; P = 0.006]. In
      addition, icodextrin use was associated with a significantly lower risk of
      technique failure (HR, 0.60; 95% CI, 0.40-0.92; P = 0.018). The icodextrin group
      had fewer technique failures due to non-compliance compared with the non
      icodextrin group whereas peritonitis- or ultrafiltration failure-related
      technique failure was not different between the two groups. CONCLUSION: This
      study further supports previous findings of long-term utilization of icodextrin
      solution improving patient and technique survival in PD patients. To confirm
      these results, a large randomized prospective study is warranted.

PMID- 21968012
TI  - Pentoxifylline decreases serum levels of tumor necrosis factor alpha, interleukin
      6 and C-reactive protein in hemodialysis patients: results of a randomized double
      blind, controlled clinical trial.
AB  - AIM: The aim of this study was to compare the effect of pentoxifylline versus
      placebo on serum concentrations of tumor necrosis factor-alpha (TNF-alpha),
      interleukin 6 (IL-6) and C-reactive protein (CRP) of hemodialysis (HD) patients.
      METHODS: This is a randomized double-blind, controlled clinical trial. HD
      patients without infection or drugs with anti-inflammatory effect were randomly
      allocated to a study (n = 18, pentoxifylline 400 mg/day) or control (n = 18,
      placebo) group; all patients had arteriovenous fistula. Besides clinical and
      laboratory monthly assessments, serum TNF-alpha and IL-6 (ELISA) and CRP
      (nephelometry) were measured at 0, 2 and 4 months. RESULTS: All the inflammation
      markers significantly (P < 0.05) decreased in the pentoxifylline group: TNF-alpha
      [baseline 0.4 (0-2) versus final 0 (0-0) pg/mL], IL-6 [baseline 9.4 (5-14) versus
      final 2.9 (2-5) pg/mL] and CRP [baseline 7.1 (3-20) versus final 2.6 (1-8) mg/L],
      whereas no significant changes were observed in the placebo group: TNF-alpha
      [baseline 0 (0-0) versus final 1.2 (0-4) pg/mL], IL-6 [baseline 8.0 (5-11) versus
      final 8.7 (4-11) pg/mL] and CRP [baseline 4.5 (2-9) versus final 3.8 (3-23)
      mg/L]. CONCLUSIONS: Pentoxifylline significantly decreased serum concentrations
      of TNF-alpha, IL-6 and CRP compared to placebo. Pentoxifylline could be a
      promising and useful strategy to reduce the systemic inflammation frequently
      observed in patients on HD.

PMID- 21968013
TI  - Polymorphisms in MYH9 are associated with diabetic nephropathy in European
      Americans.
AB  - BACKGROUND: Polymorphisms in the non-muscle myosin IIA gene (MYH9) are associated
      with focal segmental glomerulosclerosis (FSGS) and non-diabetic end-stage renal
      disease (ESRD) in African Americans and FSGS in European Americans. We tested for
      association of single nucleotide polymorphisms (SNPs) in MYH9 with T2DM-ESRD in
      European Americans; additionally, three APOL1 gene variants were evaluated.
      METHODS: Fifteen MYH9 SNPs and two APOL1 SNPs plus a 6-bp deletion were genotyped
      in 1963 European Americans, 536 cases with T2DM-ESRD and 1427 non-nephropathy
      controls (467 with T2DM and 960 without diabetes). RESULTS: Comparing T2DM-ESRD
      cases with the 467 T2DM non-nephropathy controls, single variant associations
      trending toward significance were detected with SNPs rs4821480, rs2032487 and
      rs4281481 comprising part of the major MYH9 E1 risk haplotype [P-values 0.053
      0.055 recessive, odds ratio (OR) 6.08-6.14]. Comparing T2DM-ESRD cases to all
      1427 non-nephropathy controls, we confirmed evidence of association in these
      three SNPs as well as in the fourth E1 SNP (rs3752462) (P-values 0.017-0.035, OR
      1.41-3.72). APOL1 G1/G2 nephropathy risk variants were rare in individuals of
      European American heritage, present in 0.28% of chromosomes in T2DM-ESRD cases
      and 0.32% of controls. CONCLUSIONS: MYH9 SNPs rs4821480, rs2032487, rs4281481 and
      rs3752462 are associated with T2DM-ESRD susceptibility in European Americans. The
      APOL1 risk variants are not present at appreciable frequency in this cohort with
      T2DM-ESRD. Therefore, polymorphisms in MYH9 appear to influence nephropathy risk
      in this sample.

PMID- 21968014
TI  - Distribution of glomerular IgG subclass deposits in patients with membranous
      nephropathy and anti-U1 ribonucleoprotein antibody.
AB  - BACKGROUND: It is known that a predominant glomerular deposition of IgG4 is
      characteristic of idiopathic membranous nephropathy (MN) and that significant
      deposition of other IgG subclasses is also observed in lupus MN. However, there
      is no report focusing on the distribution of glomerular IgG subclass deposits in
      MN patients with anti-U1 ribonucleoprotein (RNP) antibody. METHODS: We evaluated
      clinicopathological features and the distribution patterns of glomerular IgG
      subclass deposits in seven MN patients with positive anti-RNP antibody and
      negative antibodies to double-stranded DNA (dsDNA) and Smith antigen (Sm) (RNP-MN
      group) and in seven age- and sex-matched lupus MN patients with positive anti
      dsDNA antibody and negative antibodies to RNP and Sm (L-MN group). RESULTS: Mixed
      connective tissue disease was diagnosed in four patients in the RNP-MN group. Two
      patients in the RNP-MN group and three patients in the L-MN group developed
      nephrotic syndrome. Renal insufficiency was not present in all patients in both
      groups. Hypocomplementemia was found in two patients in the RNP-MN group and six
      patients in the L-MN group. In the RNP-MN group, positive stainings for
      glomerular IgG1, IgG2, IgG3 and IgG4 were observed in one, seven, zero and five
      patients, respectively. On the contrary, in the L-MN group, positive stainings
      for glomerular IgG1, IgG2, IgG3 and IgG4 were observed in seven, seven, seven,
      and six patients, respectively. CONCLUSIONS: This is the first study showing
      striking differences in the distribution of glomerular IgG subclass deposits
      between RNP-MN and L-MN groups. RNP-MN and L-MN may result from different
      immunological mechanisms.

PMID- 21968015
TI  - Bridging the social and the biomedical: engaging the social and political
      sciences in HIV research.
AB  - This supplement to the Journal of the International AIDS Society focuses on the
      engagement of the social and political sciences within HIV research and, in
      particular, maintaining a productive relationship between social and biomedical
      perspectives on HIV. It responds to a number of concerns raised primarily by
      social scientists, but also recognized as important by biomedical and public
      health researchers. These concerns include how best to understand the impact of
      medical technologies (such as HIV treatments, HIV testing, viral load testing,
      male circumcision, microbicides, and pre-and post-exposure prophylaxis) on sexual
      cultures, drug practices, relationships and social networks in different
      cultural, economic and political contexts. The supplement is also concerned with
      how we might examine the relationship between HIV prevention and treatment,
      understand the social and political mobilization required to tackle HIV, and
      sustain the range of disciplinary approaches needed to inform and guide responses
      to the global pandemic. The six articles included in the supplement demonstrate
      the value of fostering high quality social and political research to inform,
      guide and challenge our collaborative responses to HIV/AIDS.

PMID- 21968016
TI  - Rapamycin sensitive mTOR activation mediates nerve growth factor (NGF) induced
      cell migration and pro-survival effects against hydrogen peroxide in retinal
      pigment epithelial cells.
AB  - Patients with age related macular degeneration (AMD) have a loss of vision in the
      center of the visual field. Oxidative stress plays an important role in this
      progress. Nerve growth factor (NGF) is important for the survival and maintenance
      of sympathetic and sensory neurons and NGF eye drops improve visual acuity and
      electro-functional activity in patients with AMD. However, the molecular
      mechanisms and signaling events involved in this have not been fully
      investigated. Using cultured human retinal pigment epithelial (RPE) cells, we
      demonstrate here that NGF protects RPE cells against hydrogen peroxide (H(2)O(2))
      induced cell apoptosis. NGF also induces RPE cell migration, the latter is
      important for retinal regeneration and the recovery from AMD. H(2)O(2) decreases
      S6 phosphorylation and cell viability, which is restored by NGF. Rapamycin, the
      pharmacologic inhibitor of mammalian target of rapamycin (mTOR), diminished NGF
      induced S6 phosphorylation, cell migration and protective effects against
      oxidative stress. Collectively, we conclude that activation of rapamycin
      sensitive mTOR signaling mediates NGF induced cell migration and pro-survival
      effects in H(2)O(2) treated RPE cells.

PMID- 21968017
TI  - Ribosomal protein S3 is stabilized by sumoylation.
AB  - Human ribosomal protein S3 (rpS3) acts as a DNA repair endonuclease. The multiple
      functions of this protein are regulated by post-translational modifications
      including phosphorylation and methylation. Using a yeast-two hybrid screen, we
      identified small ubiquitin-related modifier-1 (SUMO-1) as a new interacting
      partner of rpS3. rpS3 interacted with SUMO-1 via the N- and C-terminal regions.
      We also observed sumoylation of rpS3 in Escherichia coli and mammalian cell
      systems. Furthermore, we discovered that one of three lysine residues, Lys18,
      Lys214, or Lys230, was sumoylated in rpS3. Interestingly, sumoylated rpS3 was
      resistant to proteolytic activity, indicating that SUMO-1 increased the stability
      of the rpS3 protein. We concluded that rpS3 is covalently modified by SUMO-1 and
      this post-translational modification regulates rpS3 function by increasing rpS3
      protein stability.

PMID- 21968018
TI  - Sulf2 gene is alternatively spliced in mammalian developing and tumour tissues
      with functional implications.
AB  - SULF2 enzyme regulates the activities of a number of signalling pathways that in
      many tissues are up-regulated during development and disease. As we recently
      showed for avian Sulf1, the present study demonstrates that mammalian Sulf2 gene
      can also generate functionally distinct splice variants that would regulate
      normal development and tumour growth differentially. It is thus important to
      distinguish SULF1/SULF2 isoforms in mammalian tissues to understand their
      functional and clinical relevance to disease. This study demonstrates that unlike
      normal adult lung with little or no SULF2 expression, this enzyme is expressed at
      high levels in most lung tumours showing differential cellular distribution of
      full length and shorter SULF2 variants in such tumours. Furthermore, we show that
      the short SULF2 splice variants are associated with those signalling pathways
      that are inhibited by full length SULF1/SULF2 variants and therefore could
      promote growth in such lung tumours.

PMID- 21968019
TI  - Structural modeling of RNase P RNA of the hyperthermophilic archaeon Pyrococcus
      horikoshii OT3.
AB  - Ribonuclease P (RNase P) is a ubiquitous trans-acting ribozyme that processes the
      5' leader sequence of precursor tRNA (pre-tRNA). The RNase P RNA (PhopRNA) of the
      hyperthermophilic archaeon Pyrococcus horikoshii OT3 is central to the catalytic
      process and binds five proteins (PhoPop5, PhoRpp21, PhoRpp29, PhoRpp30, and
      PhoRpp38) which contribute to the enzymatic activity of the holoenzyme. Despite
      significant progress in determining the crystal structure of the proteins, the
      structure of PhopRNA remains elusive. Comparative analysis of the RNase P RNA
      sequences and existing crystallographic structural information of the bacterial
      RNase P RNAs were combined to generate a phylogenetically supported three
      dimensional (3-D) model of the PhopRNA. The model structure shows an essentially
      flat disk with 16 tightly packed helices and a conserved face suitable for the
      binding of pre-tRNA. Moreover, the structure in solution was investigated by
      enzymatic probing and small-angle X-ray scattering (SAXS) analysis. The low
      resolution model derived from SAXS and the comparative 3-D model have similar
      overall shapes. The 3-D model provides a framework for a better understanding of
      structure-function relationships of this multifaceted primordial ribozyme.

PMID- 21968020
TI  - Involvement of brown adipose tissue in subcutaneous fat necrosis of the newborn.
AB  - BACKGROUND: Subcutaneous fat necrosis (SCFN) of the newborn is a rare condition
      that manifests within days after birth. The interscapular region, axillae and
      shoulders are the most commonly affected sites, corresponding to anatomic sites
      of brown adipose tissue (BAT) in newborns. OBJECTIVE: We postulated a specific
      involvement of BAT in SCFN and searched for brown adipocytes at affected sites.
      METHODS: Biopsy specimens were immunostained with antibodies against uncoupling
      protein 1 (UCP-1) and examined by electron microscopy. We also examined BAT by
      (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography and computed
      tomography (PET-CT) scanning. RESULTS: A few cells in biopsy specimens from two
      patients bound antibodies against UCP-1, and brown adipocytes were detected at
      several stages of degeneration. PET-CT scans revealed lower uptake of (18)F-FDG
      at major sites of SCFN. CONCLUSION: SCFN and BAT can be found at the same sites,
      suggesting a pathophysiological connection.

PMID- 21968021
TI  - Osteopontin and endostatin concentrations in peripheral blood of patients with
      adrenal tumors undergoing unilateral adrenalectomy.
AB  - Peripheral blood osteopontin (OPN) and endostatin (END) levels were studied in 35
      patients with adrenal cortex tumors and 10 patients with pheochromocytoma before
      unilateral adrenalectomy, as well as in 10 healthy subjects (controls). Thirty
      days after surgery, OPN and END were evaluated again in 16 patients with adrenal
      cortex tumors and 4 female patients with pheochromocytoma. Before surgery, OPN
      blood concentrations increased in the group of patients with adrenal cortex
      carcinomas as compared to controls (p < 0.001) and the group with Conn syndrome
      (p < 0.05); they did not change after surgery. Before adrenalectomy, OPN blood
      levels in pheochromocytoma patients were also lower than in Conn syndrome
      subjects (p < 0.05). After adrenalectomy, the normal concentrations of END
      decreased only in the group of patients with hormonally inactive cortical
      adenomas (p < 0.05). We were unable to demonstrate any relationships between
      removed tumor volumes and OPN or END blood levels.

PMID- 21968023
TI  - Modulation of abnormal synaptic transmission in hippocampal CA3 neurons of
      spontaneously epileptic rats (SERs) by levetiracetam.
AB  - Levetiracetam (LEV) inhibits partial refractory epilepsy in human, and both
      convulsive and absence-like seizures in the spontaneously epileptic rat (SER).
      Two-thirds of hippocampal CA3 neurons in SER show a long-lasting depolarization
      shift, with accompanying repetitive firing upon mossy fiber stimulation. This
      abnormal excitability is probably attributable to abnormalities in the L-type
      Ca(2+) channels. We performed electrophysiological studies to elucidate the
      mechanism underlying the antiepileptic effects of LEV via intracellular recording
      from the hippocampal CA3 neurons in slice preparations of SER and non-epileptic
      Wistar rats. LEV (100 MUM) inhibited the depolarization shift with repetitive
      firing by mossy fiber stimulation (MFS), without affecting the first spike in SER
      CA3 neurons. At a higher dose (1mM), LEV suppressed the first spike in all SER
      neurons (including the CA3 neurons which showed only a single action potential by
      MFS), while the single action potential of Wistar rat CA3 neurons remained
      unaffected. SER CA3 neurons with MFS-induced abnormal firing exhibited a higher
      number of repetitive spikes when a depolarization pulse was applied in the SER
      CA3 neurons. LEV (100 MUM, 1mM) reduced the repetitive firing induced by a
      depolarization pulse applied without affecting Ca(2+) spike in SER neurons. LEV
      is known not to bind glutamate and gamma-aminobutyric acid (GABA) receptors.
      These findings suggest that the therapeutic concentration of LEV inhibits
      abnormal firing of the CA3 neurons by modulating abnormal synaptic transmission
      and abnormal Na(+) channels in SER.

PMID- 21968022
TI  - Population-based evaluation of a suggested anatomic and clinical classification
      of congenital heart defects based on the International Paediatric and Congenital
      Cardiac Code.
AB  - BACKGROUND: Classification of the overall spectrum of congenital heart defects
      (CHD) has always been challenging, in part because of the diversity of the
      cardiac phenotypes, but also because of the oft-complex associations. The purpose
      of our study was to establish a comprehensive and easy-to-use classification of
      CHD for clinical and epidemiological studies based on the long list of the
      International Paediatric and Congenital Cardiac Code (IPCCC). METHODS: We coded
      each individual malformation using six-digit codes from the long list of IPCCC.
      We then regrouped all lesions into 10 categories and 23 subcategories according
      to a multi-dimensional approach encompassing anatomic, diagnostic and therapeutic
      criteria. This anatomic and clinical classification of congenital heart disease
      (ACC-CHD) was then applied to data acquired from a population-based cohort of
      patients with CHD in France, made up of 2867 cases (82% live births, 1.8%
      stillbirths and 16.2% pregnancy terminations). RESULTS: The majority of cases
      (79.5%) could be identified with a single IPCCC code. The category "Heterotaxy,
      including isomerism and mirror-imagery" was the only one that typically required
      more than one code for identification of cases. The two largest categories were
      "ventricular septal defects" (52%) and "anomalies of the outflow tracts and
      arterial valves" (20% of cases). CONCLUSION: Our proposed classification is not
      new, but rather a regrouping of the known spectrum of CHD into a manageable
      number of categories based on anatomic and clinical criteria. The classification
      is designed to use the code numbers of the long list of IPCCC but can accommodate
      ICD-10 codes. Its exhaustiveness, simplicity, and anatomic basis make it useful
      for clinical and epidemiologic studies, including those aimed at assessment of
      risk factors and outcomes.

PMID- 21968024
TI  - Cholinergic mechanisms of episodic memory: what specific behavioural tasks can
      tell us about specific neural mechanisms.
AB  - Understanding the neural basis of episodic memory is crucial for understanding
      how to treat memory loss in normal ageing as well as in disorders such as
      Alzheimer's disease. However, it is only recently that episodic memory has been
      able to be reliably modelled in animals allowing the biological basis to be fully
      explored. Here we review studies on the role of the cholinergic basal forebrain
      on episodic memory, and highlight differences in findings from studies in monkeys
      and rats. The results highlight the importance of choosing appropriate
      behavioural models of cognitive processes in order to understand the neural basis
      of the processes accurately.

PMID- 21968026
TI  - A prospective study of percutaneous vertebroplasty in patients with myeloma and
      spinal metastases.
AB  - AIM: To assess patient outcome in a consecutive series of patients with myeloma
      and spinal metastases who underwent percutaneous vertebroplasty. MATERIALS AND
      METHODS: Data were gathered prospectively on all patients undergoing percutaneous
      vertebroplasty between June 2001 and June 2010. Outcome measures included visual
      analogue pain scores (VAS) and Roland-Morris Questionnaire (RMQ) in patients
      treated since 2005 as well as complications and long-term outcome in all
      patients. RESULTS: One hundred and twenty-eight patients underwent percutaneous
      vertebroplasty for myeloma (n=41) or spinal metastases (n=87) over a 9 year
      period. VAS scores fell from 7.75 +/- 1.88 pre-vertebroplasty to 4.77 +/- 2.69
      post-vertebroplasty (p=0.001). RDQ scores improved from 18.55 +/- 4.79 to 13.5 +/
      6.96 (p=0.001). Complications were recorded in three patients: cement extension
      to vena cava (n=1), local haematoma (n=1), and loss of sensation over T1
      dermatome (n=1). The Kaplan-Meier estimate of 5 year survival post-vertebroplasty
      was 40% for patients with myeloma and 25% for those with metastases. CONCLUSION:
      This large prospective study demonstrates percutaneous vertebroplasty reduces
      pain and improves disability in patients from intractable pain from myeloma or
      spinal metastases and now forms an important part of the multimodality treatment
      for these patients.

PMID- 21968025
TI  - Developmental exposure to organophosphates triggers transcriptional changes in
      genes associated with Parkinson's disease in vitro and in vivo.
AB  - Epidemiologic studies support a connection between organophosphate pesticide
      exposures and subsequent risk of Parkinson's disease (PD). We used
      differentiating, neuronotypic PC12 cells to compare organophosphates
      (chlorpyrifos, diazinon), an organochlorine (dieldrin) and a metal (Ni(2+)) for
      their effects on the transcription of PD-related genes. Both of the
      organophosphates elicited significant changes in gene expression but with
      differing patterns: chlorpyrifos evoked both up- and downregulation whereas
      diazinon elicited overall reductions in expression. Dieldrin was without effect
      but Ni(2+) produced a pattern resembling that of diazinon. We then exposed
      neonatal rats to chlorpyrifos or diazinon for the first 4 days after birth and
      examined the expression of PD-related genes in the brainstem and forebrain.
      Chlorpyrifos had no significant effect whereas diazinon produced significant
      increases and decreases in expression of the same PD genes that were targeted in
      vitro. Our results provide some of the first evidence for a mechanistic
      relationship between developmental organophosphate exposure and the genes known
      to confer PD risk in humans; but they also point to disparities between different
      organophosphates that reinforce the concept that their neurotoxic actions do not
      rest solely on their shared property as cholinesterase inhibitors. The parallel
      effects of diazinon and Ni(2+) also show how otherwise unrelated developmental
      neurotoxicants can nevertheless produce similar outcomes by converging on common
      molecular pathways, further suggesting a need to examine metals such as Ni(2+) as
      potential contributors to PD risk.

PMID- 21968027
TI  - Update of carcinogenicity studies in animals and humans of 535 marketed
      pharmaceuticals.
AB  - This survey is a compendium of information retrieved on carcinogenicity in
      animals and humans of 535 marketed pharmaceuticals whose expected clinical use is
      continuous for at least 6 months or intermittent over an extended period of time.
      Of the 535 drugs, 530 have the result of at least one carcinogenicity assay in
      animals, and 279 (52.1%) of them gave a positive response in at least one assay.
      Only 186 drugs (34.8%) have retrievable information on carcinogenicity in humans,
      and 104 of them gave to a variable extent evidence of a potential carcinogenic
      activity. Concerning the correlation between results obtained in animals and
      epidemiological findings, 58 drugs gave at least one positive result in
      carcinogenicity assays performed in animals and to a variable extent displayed
      evidence of carcinogenicity in humans, but 97 drugs tested positive in animals
      and were noncarcinogenic in humans or vice versa. Our findings, which are in
      agreement with previous studies, indicate that the evaluation of the
      benefit/carcinogenic risk ratio should be always made in prescribing a drug.

PMID- 21968028
TI  - Health care access and support for disabled women in Canada: falling short of the
      UN Convention on the Rights of Persons with Disabilities: a qualitative study.
AB  - PURPOSE: The United Nations Convention on the Rights of Persons with Disabilities
      and other international human rights conventions guarantee the fundamental human
      rights to physical, social, and psychological health. The purpose of this study
      was to examine whether these rights are being upheld in Canada for disabled
      women. METHODS: An interpretive, qualitative, focus group design was employed.
      Participants were women 18 to 67 years of age with a self-identified physical,
      sensory, cognitive, and/or psychiatric impairment. Eleven focus groups were
      conducted with 74 disabled women from urban and rural settings in Northern
      Ontario, Manitoba, and Nova Scotia. The data were analyzed for themes using a
      flexible coding system derived from and consistent with the research objectives
      and the study's human rights framework. FINDINGS: Participants described multiple
      intersecting factors that impeded or facilitated access to health care. Services
      included both generic health services and impairment-specific services.
      Participants experienced a number of barriers accessing professionals, support
      programs, and services. These are described under three broad themes: 1)
      Labyrinthine health service 'systems,' 2) assumptions, attitudes, and
      discriminatory practices, and 3) inadequate sexual health or reproductive
      services and supports. CONCLUSION: The results suggest that Canada falls
      significantly short of guaranteeing disabled women's human rights to access
      health care supports and services. Access barriers resulted from the
      inefficiencies and complexities of the multiple agencies and programs that
      disabled women had to navigate, difficulties accessing information on available
      services, and negative attitudes of some health and social service providers.

PMID- 21968029
TI  - Reproductive health care utilization among young mothers in Bangladesh: does
      autonomy matter?
AB  - OBJECTIVE: To examine the linkage between the possible influences of the extent
      of autonomy on young mothers use of reproductive health care services. METHODS:
      This paper used data from the 2007 Bangladesh Demographic Health Survey. The
      analyses were based on responses of 1,778 currently married women aged 15 to 24
      years, living with at least one 0- to 35-month-old child. Utilization of
      antenatal health services (ANC) services by amount and type of provider, and
      utilization of delivery assistance according to provider type were used as proxy
      outcome variables of reproductive health care utilization. Descriptive statistics
      and multivariate logistic regression methods were employed in the analysis.
      RESULTS: Approximately one third (31%) of the currently married young women in
      Bangladesh had a higher level of overall decision-making autonomy. Only 24.0% of
      the sampled women received sufficient ANC; 54% and 18% received ANC and assisted
      deliveries from a medically trained provider. respectively. In adjusted models,
      young women who had a higher level of overall autonomy were more likely to
      receive sufficient ANC (adjusted odds ratio [AOR], 1.64; 95% confidence interval
      [CI], 1.17-2.23) and receiving ANC from medically trained provider (AOR, 1.91;
      95% CI, 1.42-2.45). Women who had medium overall autonomy were 1.40 times more
      likely (95% CI, 1.03-1.98) to have deliveries assisted by a medically trained
      provider than women who had low autonomy. CONCLUSION: Association between young
      mother's autonomy and reproductive health care utilization suggest that maternal
      autonomy needs to be considered as an important sociocultural determinant for the
      higher utilization of reproductive health care services for young mothers in
      Bangladesh.

PMID- 21968030
TI  - Gestational diabetes mellitus (GDM) screening in morbidly obese pregnant women.
AB  - OBJECTIVE: To study the outcomes of two-stage GDM screening of morbidly obese
      women in our obstetric unit and to evaluate the diagnostic performance of 20-week
      oral glucose tolerance test (OGTT) values in predicting or excluding late onset
      GDM. STUDY DESIGN: A retrospective study in which 190 pregnant women with BMI
      >=40 had two-stage screening: a 75g OGTT is performed at 20 weeks and repeated at
      28 weeks if the 20-week OGTT was normal. Receiver operating characteristic (ROC)
      curves for 20-week OGTT values were constructed in order to obtain an optimal cut
      off value of fasting and/or 2-h glucose at 20 weeks from which GDM could be
      predicted or excluded at 28 weeks. Sensitivity, specificity, positive likelihood
      ratio, and negative likelihood ratio were determined for each of the fasting and
      2-h post-load glucose values at 20 weeks. RESULTS: Forty six (24%) women were
      diagnosed with GDM. Thirty-two (70%) were diagnosed at 20 weeks and 14 (30%) at
      28 weeks. The 2-h cut-off value of >=6mmol/l at the 20-week OGTT had a negative
      likelihood ratio of 0.12 to predict GDM at 28 weeks. The low negative likelihood
      ratio reduces the probability of detecting GDM at 28 weeks from 9% (pre-test
      probability) to 1% (post-test probability). CONCLUSION: Nearly 70% of the women
      were diagnosed with GDM at 20 weeks, which gives an early opportunity to treat
      maternal hyperglycaemia with consequent health benefits. A 2-h cut-off glucose
      value of 6mmol/l at 20 weeks OGTT has a low negative likelihood ratio which
      virtually excludes GDM at 28 weeks. Hence women with a 2h value of <6mmol/l at 20
      weeks can avoid a repeat 28 week OGTT test.

PMID- 21968031
TI  - Does forceps training on a birth simulator allow obstetricians to improve forceps
      blade placement?
AB  - OBJECTIVE: The aim of this study was to evaluate whether forceps training on a
      birth simulator allows obstetricians to improve forceps blade placement. STUDY
      DESIGN: Analysis was based on 600 forceps blade placements performed by ten
      trainees on a simulator. The trajectories used by the trainees were assessed
      using reference spheres that reflected an optimal bimalar placement. Three
      definitions of success were used: small-sphere success, medium-sphere success and
      large-sphere success were respectively defined by the forceps blade tip being
      within 5, 10 or 15mm of the center of the sphere (the small-sphere being nested
      within the medium-sphere and the small and medium being nested within the large
      sphere). Wilcoxon paired analysis was performed to compare the first (50
      trajectories) and final (50 trajectories) sets of five forceps placements.
      Graphical representation and linear regression were used to visualize the
      learning process. RESULTS: 596 trajectories were available for analysis. During
      the last set of five forceps the success rate was respectively 28%, 72% and 86%
      for small-sphere, medium-sphere and large-sphere success with the right blade and
      8%, 32% and 70% for the left blade. Wilcoxon analysis showed a highly significant
      improvement for all kinds of success in the right blade and for large-sphere
      success in the left blade. Linear regression slopes were significant. Using a
      projection, the theoretical numbers of placements needed to achieve a 100%
      success rate for small-sphere, medium-sphere and large-sphere were respectively
      80, 45 and 35. CONCLUSION: These results strongly suggest that performing forceps
      blade placement on birth simulator allows obstetricians to improve their skills.

PMID- 21968032
TI  - Rapid large-scale preparation of ZnO nanowires for photocatalytic application.
AB  - ZnO nanowires are a promising nanomaterial for applications in the fields of
      photocatalysis, nano-optoelectronics, and reinforced composite materials.
      However, the challenge of producing large-scale ZnO nanowires has stunted the
      development and practical utilization of ZnO nanowires. In this study, a modified
      carbothermal reduction method for preparing large-scale ZnO nanowires in less
      than 5 min is reported. The preparation was performed in a quartz tube furnace at
      atmospheric pressure without using any catalysts. A mixed gas of air and N2 with
      a volume ratio of 45:1 was used as the reactive and carrier gas. About 0.8 g ZnO
      nanowires was obtained using 1 g ZnO and 1 g graphite powder as source materials.
      The obtained nanowires exhibited a hexagonal wurtzite crystal structure with an
      average diameter of about 33 nm. Good photocatalytic activity of the nanowires
      toward the photodegradation of methylene blue dye under UV irradiation was also
      demonstrated.

PMID- 21968033
TI  - Freezer or non-freezer: clinical assessment of freezing of gait.
AB  - INTRODUCTION: Freezing of gait (FOG) is both common and debilitating in patients
      with Parkinson's disease (PD). Future pathophysiology studies will depend
      critically upon adequate classification of patients as being either 'freezers' or
      'non-freezers'. This classification should be based ideally upon objective
      confirmation by an experienced observer during clinical assessment. Given the
      known difficulties to elicit FOG when examining patients, we aimed to investigate
      which simple clinical test would be the most sensitive to provoke FOG
      objectively. METHODS: We examined 50 patients with PD, including 32 off-state
      freezers (defined as experiencing subjective 'gluing of the feet to the floor').
      Assessment including a FOG trajectory (three trials: normal speed, fast speed,
      and with dual tasking) and several turning variants (180 degrees  vs. 360 degrees
      turns; leftward vs. rightward turns; wide vs. narrow turning; and slow vs. fast
      turns). RESULTS: Sensitivity of the entire assessment to provoke FOG in
      subjective freezers was 0.74, specificity was 0.94. The most effective test to
      provoke FOG was rapid 360 degrees  turns in both directions and, if negative,
      combined with a gait trajectory with dual tasking. Repeated testing improved the
      diagnostic yield. The least informative tests included wide turns, 180 degrees 
      turns or normal speed full turns. Sensitivity to provoke objective FOG in
      subjective freezers was 0.65 for the rapid full turns in both directions and 0.63
      for the FOG trajectory. DISCUSSION: The most efficient way to objectively
      ascertain FOG is asking patients to repeatedly make rapid 360 degrees  narrow
      turns from standstill, on the spot and in both directions.

PMID- 21968034
TI  - The Senior Fitness Test as a functional measure in Parkinson's disease: a pilot
      study.
AB  - OBJECTIVE: This pilot study aimed to determine if the Senior Fitness Test (SFT)
      battery can be applied to subjects with Parkinson's disease (PD) and whether its
      results can be reliable indicators of disease severity. METHODS: Thirty people
      with mild to moderate PD performed the SFT and completed the Parkinson's Disease
      Questionnaire (PDQ-39) and the Unified Parkinson's Disease Rating Scale (UPDRS).
      To compare the metric properties of the SFT battery with the UPDRS and the PDQ
      39, a SFT sum-score was created. RESULTS: The tests that compose the SFT were
      successfully completed by the patients, except for the "Two-Minute Step Test"
      (2MST), which had to be shortened. We observed a strong correlation among the
      SFT's sum-score and the total scores of the PDQ-39 and the UPDRS. Some
      correlation was also found among the SFT's sum-score and the analyzed subscales,
      except for those assessing mental and cognitive levels. CONCLUSION: The SFT
      appears to be a useful tool to assess functional fitness in people with PD: it
      can be carried out in the clinical setting albeit with some minor modifications.
      However, its validity as an indicator of disease severity remains to be
      confirmed.

PMID- 21968035
TI  - Pretreatment with human serum butyrylcholinesterase alone prevents cardiac
      abnormalities, seizures, and death in Gottingen minipigs exposed to sarin vapor.
AB  - Human serum butyrylcholinesterase (Hu BChE) is a stoichiometric bioscavenger that
      is being developed as a prophylactic countermeasure against organophosphorus
      nerve agents. This study was designed to evaluate the efficacy of Hu BChE against
      whole-body inhalation exposure to a lethal dose of sarin (GB) vapor. Male
      Gottingen minipigs were subjected to: air exposure, GB vapor exposure, or
      pretreatment with Hu BChE followed by GB vapor exposure. Hu BChE was administered
      by i.m. injection 24 h prior to exposure to 4.1 mg/m(3) of GB vapor for 60 min.
      Electrocardiograms (ECG), electroencephalograms (EEG), and pupil size were
      recorded throughout exposure. Blood drawn before and throughout exposure was
      analyzed for blood gases, electrolytes, metabolites, acetylcholinesterase and
      BChE activities, and amount of GB present. Untreated animals exposed to GB vapor
      exhibited cardiac abnormalities and generalized seizures, ultimately succumbing
      to respiratory failure. Pretreatment with 3.0 or 6.5 mg/kg of Hu BChE delayed
      blood gas and acid-base disturbances and the onset of cardiac and neural toxic
      signs, but failed to increase survivability. Pretreatment with 7.5 mg/kg of Hu
      BChE, however, completely prevented toxic signs, with blood chemistry and ECG and
      EEG parameters indistinguishable from control during and after GB exposure. GB
      bound in plasma was 200-fold higher than plasma from pigs that did not receive Hu
      BChE, suggesting that Hu BChE scavenged GB in blood and prevented it from
      reaching other tissues. Thus, prophylaxis with Hu BChE alone not only increased
      survivability, but also prevented cardiac abnormalities and neural toxicity in
      minipigs exposed to a lethal dose of GB vapor.

PMID- 21968037
TI  - Oversampling method to extract excitatory and inhibitory conductances from single
      trial membrane potential recordings.
AB  - Variations of excitatory and inhibitory conductances determine the membrane
      potential (V(m)) activity of neurons, as well as their spike responses, and are
      thus of primary importance. Methods to estimate these conductances require
      clamping the cell at several different levels of V(m), thus making it impossible
      to estimate conductances from "single trial" V(m) recordings. We present here a
      new method that allows extracting estimates of the full time course of excitatory
      and inhibitory conductances from single-trial V(m) recordings. This method is
      based on oversampling of the V(m). We test the method numerically using models of
      increasing complexity. Finally, the method is evaluated using controlled
      conductance injection in cortical neurons in vitro using the dynamic-clamp
      technique. This conductance extraction method should be very useful for future in
      vivo applications.

PMID- 21968036
TI  - Plate reader-based assays for measuring cell viability, neuroprotection and
      calcium in primary neuronal cultures.
AB  - Drug discovery and development efforts critically rely on cell-based assays for
      high-throughput screening. These assay systems mostly utilize immortalized cell
      lines, such as human embryonic kidney cells, and can provide information on
      cytotoxicity and cell viability, permeability and uptake of compounds as well as
      receptor pharmacology. While this approach has proven extremely useful for single
      target pharmacology, there is an urgent need for neuropharmacological studies to
      screen novel drug candidates in a cellular environment resembles neurons in vivo
      more closely, in order to gain insight into the involvement of multiple signaling
      pathways. Primary cultured neuronal cells, such as cortical neurons, have long
      been used for basic research and low-throughput screening and assay development,
      and may thus be suitable candidates for the development of neuropharmacological
      high-throughput screening approaches. We here developed and optimized protocols
      for the use of primary cortical neuronal cells in high-throughput assays for
      neuropharmacology and neuroprotection, including calcium mobilization,
      cytotoxicity and viability as well as ion channel pharmacology. Our data show low
      inter-experimental variability and similar reproducibility as conventional cell
      line assays. We conclude that primary neuronal cultures provide a viable
      alternative to cell lines in high-throughput assay systems by providing a
      cellular environment more closely resembling physiological conditions in the
      central nervous system.

PMID- 21968038
TI  - Epistemic fault lines in biomedical and social approaches to HIV prevention.
AB  - This paper raises the question of how knowledge creation is organized in the area
      of HIV prevention and how this concatenation of expertise, resources, at-risk
      people and viruses shapes the knowledge used to impede the epidemic. It also
      seeks to trouble the discourses of biomedical pre-eminence in the field of HIV
      prevention by examining the claim for treatment as prevention, looking at
      evidence constructed through the biomedical frame and through the lens of the
      sociology of science. These questions lie within a larger socio-historical
      context of lagging worldwide attention and funding to prevention in the HIV area
      and, in particular, neglect of populations at greatest risk. Much contemporary
      HIV prevention research relies on a population science divided over an epistemic
      fault line from the communities and individuals who must make sense of the
      intrusion of a life-threatening disease into their pursuit of pleasure and
      intimacy. There are, nevertheless, lessons to be learned from prevention success
      stories among sex workers, injection drug users, and gay and bisexual men. The
      success stories point to a need for a robust social science agenda that examines:
      the ways that people are socially organized and networked; the popular strategies
      and folk wisdoms developed in the face of HIV risk; socio-historical movement of
      sexual and drug cultures; the dynamics of popular mobilization to advance health;
      the institutional sources of HIV discourses; and popular understandings of HIV
      technologies and messages.

PMID- 21968039
TI  - Regulation: too much or too little?

PMID- 21968040
TI  - A preliminary investigation into the effect of the use of the Short Message
      Service (SMS) on patient attendance at an NHS Dental Access Centre in Scotland.
AB  - AIM: This study's aim was to assess whether the use of Short Message Service
      (SMS) text reminders sent to patients prior to their dental appointments improved
      attendance rates for two dentists at a dental access centre in Kirkcaldy, Fife,
      Scotland. METHOD: Automated  SMS text reminders were set up through practice
      management software at Kirkcaldy Dental Access Centre. Two audits, using a
      research methodology, were then performed. Failure to attend appointments with
      the two dentists at 150 consecutive appointments was assessed before and after
      implementing  the SMS text reminders. The null hypothesis that SMS reminders do
      not improve attendance rates at the dental access centre was tested. The Yates'
      corrected chi-square test was applied to the resulting data, with the level for
      statistical significance set at P<0.05. RESULTS: Patients readily accepted the
      text messages and found them to be non-intrusive. Failed attendance at
      appointments for the two dentists was reduced from 46/150 (31%) before the SMS
      text reminders were introduced to 21/150 (14%) after its introduction
      (P=0.00088). Thus the use of SMS  text reminders resulted in a statistically
      significant reduction in the number of failed attendances at appointments for the
      two dentists. CONCLUSIONS: In this preliminary study, SMS appointment reminders
      reduced the number of failed appointments significantly. They can provide  an
      automated, non-intrusive, and cost-effective method of improving patient
      attendance at dental appointments.

PMID- 21968041
TI  - Access: what exactly is the problem? report of a symposium held at the Royal
      College of Surgeons of England on 31st May 2011.

PMID- 21968042
TI  - Proposed career pathway for clinical academic general dental practitioners.
AB  - The Modernising Medical Careers framework provides the opportunity for both
      medical specialists and general medical practitioners to follow training pathways
      that lead to appointments as National Health Service (NHS) consultants and to
      senior academic posts. Similar opportunities are  available for dentists who wish
      to specialise. However, they are not available to dentists working in primary
      dental care who wish to become NHS consultants or senior academics in general
      dentistry. An alternative pathway is required that does not force committed
      primary care dentists who  wish to become NHS consultants or senior academics
      down a path of specialisation. In this paper, the authors explore the situation
      in some detail and propose a career pathway with appropriate competencies for
      primary care dentists who aspire to become NHS consultants or senior academics.
      They  justify why such posts should be created. The competencies have been
      developed using key guidelines and documents from the European Bologna Process
      and the Association for Dental Education in Europe, the Curriculum for UK Dental
      Foundation Programme Training, and the General Dental Council  monospecialty
      curricula. It is hoped that the proposed pathway will produce highly trained
      generalists who will: (a) encourage and undertake research in primary dental
      care, where over 90% of dentistry is delivered, (b) support and lead outreach
      centres so that teaching and clinical cases  reflect primary dental care, where
      students will spend their working lives post-qualification, and (c) provide a
      means of increasing the numbers of clinical dental academics, which have been in
      decline over the last 10 years.

PMID- 21968043
TI  - Complications associated with intravenous midazolam sedation in anxious dental
      patients.
AB  - AIM: This prospective study was designed to establish the nature, frequency and
      sequelae of complications arising in patients receiving dental treatment under
      intravenous midazolam sedation. METHODS: All patients attending the Sedation
      Department at New-castle Dental  Hospital for intravenous sedation over a six
      month period were audited. A standardised data-collection pro forma was designed
      in order to collect data relating to the patient, the sedation episode, the
      dental treatment and any complications arising. The published standard used in
      this study  states that the incidence of complications should be no more than 8%.
      RESULTS: Four hundred and one patients were included. The mean dose of midazolam
      administered was 7.6 mg with a mean titration rate of 0.9 mg/min. Complications
      were reported in 12 patients (3%), 11 of which were  minor and one moderate. All
      complications were managed successfully within the department with no lasting
      sequelae. Treatment was completed in 382 (95.7%) patients, with failure to
      complete treatment in 17 (4.3%) patients due to disinhibition (1), poor
      cooperation (10), and the sedation wearing  off (6). CONCLUSION: The standard was
      met because complications arising were infrequent (3%) and predominantly minor in
      nature. Complications were managed conservatively and effectively, with all
      patients being discharged home the same day with no lasting sequelae. The study
      demonstrates  that intravenous midazolam provides a safe sedation technique,
      suitable for adult dental patients in primary care, when administered by trained
      personnel on carefully selected patients and in accordance with nationally agreed
      protocols and guidelines.

PMID- 21968044
TI  - Ehlers-Danlos syndrome (classic type): report of a case presenting with an
      unusual dental anomaly.
AB  - Ehlers-Danlos syndrome (EDS) comprises a group of generalised connective tissue
      disorders. Deficiency or alteration of the collagen present in the tissues
      results in some classic signs such as skin hyper extensibility, joint
      hypermobility, and vascular fragility. Multiple supernumerary  teeth,
      congenitally missing teeth, and odontogenic keratocysts have been reported in
      some patients with EDS. To the author's knowledge, transposition of permanent
      canines has not previously been reported in any case of EDS. This case report
      presents the dental findings of a sporadic case of  classic-type EDS in a 14-year
      old Chinese male who had transposition of a permanent maxillary canine as well as
      the presence of two supernumerary premolars in the mandible.

PMID- 21968045
TI  - Self-reported oral health status of adults resident in Medway, Kent in 2009.
AB  - AIM: In order to assess the oral health status, oral behaviours and use of oral
      healthcare services of the adult population of Medway (Kent) in 2009, NHS Medway
      commissioned an assessment. Its aims were to understand oral health and impacts,
      behaviours and the use of dental services  in order to inform future development
      of dental services. METHODS: A self-reported postal questionnaire survey using
      relevant questions from the 1998 national Adult Dental Health Survey (ADHS) was
      performed. A stratified sample was drawn from all those aged 16 years and over,
      living  in Medway and registered with a general medical practice. Stratification
      was into the three areas within Medway (Chatham, Gillingham and Rainham, and
      Rochester and Strood). Where appropriate, respondents answered the questions
      using a five-point Likert scale. The resulting data were analysed  by area of
      domicile, age, gender, and deprivation. RESULTS: Eight thousand questionnaires
      were sent out, of which 3101 (39%) were returned. Because of this low response
      and the need to weight responses to represent the distribution of the Medway
      population, this investigation must  be considered as a service evaluation rather
      than a research project. Of respondents, 4% were edentate, 16% had 1-20 teeth,
      and 80% had 21 or more teeth. Fifty-one per cent of respondents reported at least
      one oral health impact; most commonly this was physical pain and psychological
      discomfort;  least commonly, social disability and handicap. Sixteen per cent
      reported that their last dental visit was over 24 months ago and 31% reported
      that they attended only when in trouble or never (most commonly, because of
      anxiety and cost). There were marked variations in oral health status and  use of
      dental services between those living in the most and least deprived areas.
      CONCLUSIONS: * Medway adults were more likely than the 2009 national ADHS
      respondents to be dentate but less likely to have 21 or more teeth.  *Oral health
      impacts have been substantial,  especially the experience of physical pain. 
      *Proportionately more people than the 2009 national ADHS respondents reported
      attending a dentist in the previous 24 months. The most common reasons for non
      attendance were anxiety and cost.  *These findings have implications for  the
      future development of the Medway oral health strategy and for all those working
      in primary care dentistry.

PMID- 21968046
TI  - An introduction to research for primary dental care clinicians part 6: stage 7.
      Piloting the methodology and project management.

PMID- 21968047
TI  - Improvement in survival of older adults with multiple myeloma: results of an
      updated period analysis of SEER data.
AB  - BACKGROUND: Treatment of multiple myeloma has changed significantly over the past
      several years with clinical trials reporting superior survival results using
      newer agents. Previous work has shown that the survival rate has improved for
      younger, but not older, patients with myeloma. Here, we update survival estimates
      for patients with myeloma in the early 21st century to determine whether
      continued improvement can be seen on a population level and whether or not it now
      extends to older patients. METHODS: Using period analysis to examine data from
      the Surveillance, Epidemiology, and End Results database, we estimate changes in
      the 5- and 10-year relative survival rates (RSRs) from 1998-2002 to 2003-2007.
      RESULTS: The 5- and 10-year RSRs have improved for patients with myeloma overall,
      from 32.8% and 15% in 1998-2002 to 40.3% and 20.8%, respectively, in 2003-2007.
      The greatest improvements were observed for patients aged 15-44 years, with 5-
      and 10-year RSRs reaching >70% and ~50%, respectively, but improvements were also
      seen for patients aged >70 years. CONCLUSION: Overall, survival continues to
      improve for patients with myeloma, including older patients, suggesting that
      newer treatment options continue to make a population-wide impact.

PMID- 21968048
TI  - Pitfalls in the quest of neuroprotectants for the perinatal brain.
AB  - Sick preterm and term newborns are highly vulnerable to neural injury, and thus
      there has been a major search for new, safe and efficacious neuroprotective
      interventions in recent decades. Preclinical studies are essential to select
      candidate drugs for clinical trials in humans. This article focuses on 'negative'
      preclinical studies, i.e. studies where significant differences cannot be
      detected. Such findings are critical to inform both clinical and preclinical
      investigators, but historically they have been difficult to publish. A
      significant amount of time and resources is lost when negative results or
      nonpromising therapeutics are replicated in separate laboratories because these
      negative results were not shared with the research community in an open and
      accessible format. In this article, we discuss approaches to strengthen
      conclusions from negative preclinical studies and, conversely, to reduce false
      negative preclinical evaluations of potential therapeutic compounds. Without
      being exhaustive, we address three major issues in conducting and interpreting
      preclinical experiments, including: (a) the choice of animal models, (b) the
      experimental design, and (c) issues concerning statistical analyses of the
      experiments. This general introduction is followed by synopses of negative data
      obtained from studies of three potential therapeutics for perinatal brain injury:
      (1) the somatostatin analog octreotide, (2) an AMPA/kainate receptor antagonist,
      topiramate, and (3) a pyruvate derivative, ethyl pyruvate.

PMID- 21968049
TI  - Antitumor effect of dehydroxymethylepoxyquinomicin, a small molecule inhibitor of
      nuclear factor-kappaB, on glioblastoma.
AB  - Glioblastoma is the most malignant type of brain tumor. Despite recent advances
      in therapeutic modalities, the prognosis of glioblastoma remains very poor.
      Recent studies have indicated that RelA/nuclear factor (NF)-kappaB is
      consistently activated in human glioblastoma. In this study, we searched for a
      new treatment modality for glioblastoma, by examining the effects of
      dehydroxymethylepoxyquinomicin (DHMEQ), a unique small molecule inhibitor of NF
      kappaB. Addition of DHMEQ to cultured human glioblastoma cells inhibited the
      nuclear translocation of RelA. It also reduced the growth rate of human
      glioblastoma cells significantly in 6 cell lines and modestly in 3 among 10 cell
      lines examined. Then, we performed further analyses using 3 sensitive cell lines
      (U87, U251, and YKG-1). The growth retardation was accompanied by G2/M arrest in
      vitro. Increased apoptosis was observed in U87 and YKG-1, but not U251 cells
      after DHMEQ treatment. Then, we tested the efficacy of DHMEQ in chemoprevention
      through the use of a nude mouse model. Subcutaneous tumors formed by U87 or U251
      cells were reduced by ~40% in size by intraperitoneal administration of DHMEQ
      started immediately after implantation of the cells. DHMEQ treatment achieved
      statistically significant improvements in survival curves of mice intracranially
      implanted with U87 or U251 cells. Histological analysis revealed increased areas
      of necrosis, increased numbers of collapsed microvessels, decreased nuclear
      immunoreactivity of RelA, and decreased immunoreactivity of urokinase-type
      plasminogen activator in the DHMEQ-treated U87 tumor tissues. These results
      suggest that the targeting of NF-kappaB by DHMEQ may serve as a promising
      treatment modality in glioblastoma.

PMID- 21968050
TI  - Choosing the best animal species to mimic clinical colon anastomotic leakage in
      humans: a qualitative systematic review.
AB  - BACKGROUND/AIMS: Animal models are valuable for studying pathogenic factors and
      preventive measures for colon anastomotic leakage. The suitability of the species
      as models varies greatly; however, no consensus exists on which species to use.
      The aim of this review was to evaluate different experimental animals for the
      study of clinical colon anastomotic leakage. METHODS: PubMed and REX database
      were searched up to October 2010 to identify studies evaluating clinical colon
      anastomotic leakage in animal models and textbooks on experimental animals,
      respectively. RESULTS: Functional models of clinical colon anastomotic leakage
      have been developed in the mouse, pig, rat, dog and rabbit. However, extreme
      interventions are needed in order to produce clinical leakage in the rat.
      CONCLUSION: Despite the wide use of the rat in this field of research, it seems
      that its resistance to intra-abdominal infection makes clinical leakage difficult
      to produce thus rendering the rat unsuited as a model. On the basis of the
      available literature, we recommend using mice as models mimicking clinical colon
      anastomotic leakage. Pigs may be an alternative; however, the existing models in
      this animal are less validated and clinically relevant.

PMID- 21968051
TI  - Sheehan's syndrome with pancytopenia: a case report and review of the literature.
AB  - INTRODUCTION: Sheehan's syndrome is defined by varying degrees of anterior
      pituitary deficiency due to postpartum ischemic necrosis of the pituitary gland
      after massive bleeding. It is a rare disorder in western countries and even in
      Tunisia. Hematologic abnormalities such as normochromic anemia have been reported
      in these patients. However, pancytopenia is rarely observed. CASE PRESENTATION:
      We describe the case of a 48-year-old Tunisian woman with features of
      hypopituitarism. Laboratory tests showed pancytopenia that was completely
      reversed after adequate hormone replacement. CONCLUSION: Clinicians should
      consider the possibility of hypopituitarism as a cause of pancytopenia. This is
      an original case report that is of interest to hematologists, who should be aware
      of Sheehan's syndrome as a treatable etiology of pancytopenia for women.

PMID- 21968052
TI  - Cysteine: the Fun-Ke nutraceutical.

PMID- 21968053
TI  - Biomarkers of endothelial cell activation: candidate markers for drug-induced
      vasculitis in patients or drug-induced vascular injury in animals.
AB  - There is a pressing need for vascular biomarkers for studies of drug-induced
      vasculitis in patients and drug-induced vascular injury (DIVI) in animals. We
      previously reviewed a variety of candidate biomarkers of endothelial cell (EC)
      activation (Zhang et al., 2010). Now we update information on EC activation
      biomarkers from animal data on DIVI and clinical data of vasculitic patients,
      particularly patients with primary antineutrophil cytoplasmic autoantibody (ANCA)
      associated small vessel vasculitis (primary AAVs), including Wegener's
      granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome and necrotizing
      crescentic glomerulonephritis. Drug-associated ANCA-positive small vessel
      vasculitis (drug-AAVs) can closely resemble primary AAVs, suggesting the large
      overlap between primary idiopathic systemic vasculitis and drug-induced
      vasculitis. AAVs in patients and DIVI in animals vary considerably; however,
      there is close resemblance between AAVs and DIVI in some respects: (1) the
      immunopathogenetic mechanisms (activation of primed neutrophils, ECs and T cells
      by ANCA in patients and activation of ECs, mast cells, and macrophages by drugs
      in animals); (2) the morphologic changes (fibrinoid necrosis of the vessel wall
      and neutrophilic infiltration); (3) the preferable sites (small arteries,
      arterioles, capillaries and venules); and (4) elevation of vascular biomarkers
      suggestive of an endothelial origin. The present review discusses soluble and
      cell component biomarkers and provides a rationale for the potential utility of
      EC activation biomarkers in nonclinical and clinical studies during new drug
      development. Further investigation, however, is needed to assess their potential
      utility.

PMID- 21968054
TI  - Alteration of autobiographical memory in amnestic mild cognitive impairment.
AB  - The concept of amnestic mild cognitive impairment (aMCI) concerns a population of
      older individuals at high risk of developing probable Alzheimer's disease.
      Although anterograde memory deficits have been largely documented in patients
      with aMCI, little is known about the integrity of their autobiographical memory
      (AuM). This study aimed at evaluating AuM in aMCI individuals and at
      investigating whether their ability to retrieve AuMs varied as a function of
      whether the tests used required recognition or effortful retrieval processes.
      Fourteen aMCI patients and 14 matched controls underwent a standard
      neuropsychological evaluation and an extensive autobiographical assessment. AuM
      was explored using verbal material, the Autobiographical Memory Interview, and a
      visual task of personal photographs. Together, these tests tapped the semantic
      and episodic components of AuM and different cognitive processes involved in
      retrieval (recall and recognition). Results indicate that AuM is altered in aMCI
      patients. This impairment affects both episodic and semantic components of AuM,
      and is characterized by a general difficulty in recollecting personal episodes
      covering the entire lifespan, along with a loss of recognition of recently
      experienced episodes. Furthermore, recollection of personal episodes was
      correlated with scores on tests requiring retrieval abilities, while recognition
      of familiar photographs was correlated with scores on tests assessing
      encoding/storage of new information. Results suggest that the AuM deficit in aMCI
      patients may result from the combination of two mechanisms, an anterograde memory
      impairment impeding the storage of newly experienced events, and a global
      alteration of recollection affecting the recall of AuM covering all periods of
      life. Alteration of these processes may possibly be related to the progression
      and distribution of the neuropathological lesions in medial temporal and frontal
      lobe structures found in Alzheimer's disease.

PMID- 21968055
TI  - Why we should integrate behavioral and neuroimaging studies to examine neural
      plasticity in perceptual learning.

PMID- 21968056
TI  - Carboxylesterases from the seeds of an underutilized legume, Mucuna pruriens;
      isolation, purification and characterization.
AB  - Two carboxylesterases (ME-III and ME-IV) have been purified to apparent
      homogeneity from the seeds of Mucuna pruriens employing ammonium sulfate
      fractionation, cation exchange chromatography on CM-cellulose, gel-permeation
      chromatography on Sephadex G-100 and preparative PAGE. The homogeneity of the
      purified preparations was confirmed by polyacrylamide gel electrophoresis (PAGE),
      gel-electrofocussing and SDS-PAGE. The molecular weights determined by gel
      permeation chromatography on Sephadex G-200 were 20.89 kDa (ME-III) and 31.62 kDa
      (ME-IV). The molecular weights determined by SDS-PAGE both in the presence and
      absence of 2-mercaptoethanol were 21 kDa (ME-III) and 30.2 kDa (ME-IV)
      respectively, suggesting a monomeric structure for both the enzymes. The enzymes
      were found to have Stokes radius of 2.4 nm (ME-III) and 2.7 nm (ME-IV). The
      isoelectric pH values of the enzymes, ME-III and ME-IV, were 6.8 and 7.4,
      respectively. ME-III and ME-IV were classified as carboxylesterases employing
      PAGE in conjunction with substrate and inhibitor specificity. The K(m) of ME-III
      and ME-IV with 1-naphthyl acetate as substrate was 0.1 and 0.166 mM while with 1
      naphthyl propionate as substrate the K(m) was 0.052 and 0.0454 mM, respectively.
      As the carbon chain length of the acyl group increased, the affinity of the
      substrate to the enzyme increased indicating hydrophobic nature of the acyl group
      binding site. The enzymes exhibited an optimum temperature of 45 degrees C (ME
      III) and 37 degrees C (ME-IV), an optimum pH of 7.0 (ME-III) and 7.5 (ME-IV) and
      both the enzymes (ME-III and ME-IV) were stable up to 120 min at 35 degrees C.
      Both the enzymes were inhibited by organophosphates (dichlorvos and
      phosphamidon), but resistant towards carbamates (carbaryl and eserine sulfate)
      and sulphydryl inhibitors (p-chloromercuricbenzoate, PCMB).

PMID- 21968057
TI  - The deinococcal DdrB protein is involved in an early step of DNA double strand
      break repair and in plasmid transformation through its single-strand annealing
      activity.
AB  - The Deinococcus radiodurans bacterium exhibits an extreme resistance to ionizing
      radiation. Here, we investigated the in vivo role of DdrB, a radiation-induced
      Deinococcus specific protein that was previously shown to exhibit some in vitro
      properties akin to those of SSB protein from Escherichia coli but also to promote
      annealing of single stranded DNA. First we report that the deletion of the C
      terminal motif of the DdrB protein, which is similar to the SSB C-terminal motif
      involved in recruitment to DNA of repair proteins, did neither affect cell
      radioresistance nor DNA binding properties of purified DdrB protein. We show
      that, in spite of their different quaternary structure, DdrB and SSB occlude the
      same amount of ssDNA in vitro. We also show that DdrB is recruited early and
      transiently after irradiation into the nucleoid to form discrete foci. Absence of
      DdrB increased the lag phase of the extended synthesis-dependent strand annealing
      (ESDSA) process, affecting neither the rate of DNA synthesis nor the efficiency
      of fragment reassembly, as indicated by monitoring DNA synthesis and genome
      reconstitution in cells exposed to a sub-lethal ionizing radiation dose.
      Moreover, cells devoid of DdrB were affected in the establishment of plasmid DNA
      during natural transformation, a process that requires pairing of internalized
      plasmid single stranded DNA fragments, whereas they were proficient in
      transformation by a chromosomal DNA marker that integrates into the host
      chromosome through homologous recombination. Our data are consistent with a model
      in which DdrB participates in an early step of DNA double strand break repair in
      cells exposed to very high radiation doses. DdrB might facilitate the accurate
      assembly of the myriad of small fragments generated by extreme radiation exposure
      through a single strand annealing (SSA) process to generate suitable substrates
      for subsequent ESDSA-promoted genome reconstitution.

PMID- 21968058
TI  - CHL-1 provides an essential function affecting cell proliferation and chromosome
      stability in Caenorhabditis elegans.
AB  - A family of helicases that are important in maintaining genome stability is the
      iron-sulfur group. Members of this family include DOG-1/FANCJ, RTEL1, XPD and
      Chl1p/DDX11. In Caenorhabitis elegans, the predicted gene M03C11.2 has orthology
      to the CHL1 (Chromosome loss 1) gene in Saccharomyces cerevisiae and DDX11
      (DEAD/H box polypeptide 11) in humans. In this paper, we show that the chl-1 gene
      in C. elegans is required for normal development and fertility. Mutants have
      lineage-independent cell proliferation defects that result in a Stu (sterile
      uncoordinated) phenotype, characterized by gonadal abnormalities and a reduced
      number of D motor neurons and seam cells. A chromosome stability defect is
      present in the germ cells, where an abnormal number of DAPI-staining chromosomes
      appear in diakinesis. CHL-1 function is required for the integrity of poly
      guanine/poly-cytosine DNA in the absence of DOG-1/FANCJ: the loss of CHL-1 alone
      does not result in the deletion of G-tracts, but it does increase the number of
      deletions observed in the dog-1; chl-1 double mutant, indicating a role for CHL-1
      during replication and repair. In addition, we observed that cohesin defects
      increased the number of deletions in the absence of DOG-1/FANCJ. Our results
      demonstrate a role for CHL-1 in cell proliferation and maintaining normal
      chromosome numbers, and implicate CHL-1 in chromosome stability and repair of
      unresolved secondary structures during replication.

PMID- 21968059
TI  - A role for SUMO in nucleotide excision repair.
AB  - The two Siz/PIAS SUMO E3 ligases Siz1 and Siz2 are responsible for the vast
      majority of sumoylation in Saccharomyces cerevisiae. We found that siz1Delta
      siz2Delta mutants are sensitive to ultra-violet (UV) light. Epistasis analysis
      showed that the SIZ genes act in the nucleotide excision repair (NER) pathway,
      and suggested that they participate both in global genome repair (GGR) and in the
      Rpb9-dependent subpathway of transcription-coupled repair (TCR), but have minimal
      role in Rad26-dependent TCR. Quantitative analysis of NER at the single
      nucleotide level showed that siz1Delta siz2Delta is deficient in repair of both
      the transcribed and non-transcribed strands of the DNA. These experiments
      confirmed that the SIZ genes participate in GGR. Their role in TCR remains
      unclear. It has been reported previously that mutants deficient for the SUMO
      conjugating enzyme Ubc9 contain reduced levels of Rad4, the yeast homolog of
      human XPC. However, our experiments do not support the conclusion that SUMO
      conjugation affects Rad4 levels. We found that several factors that participate
      in NER are sumoylated, including Rad4, Rad16, Rad7, Rad1, Rad10, Ssl2, Rad3, and
      Rpb4. Although Rad16 was heavily sumoylated, elimination of the major SUMO
      attachment sites in Rad16 had no detectable effect on UV resistance or removal of
      DNA lesions. SUMO attachment to most of these NER factors was significantly
      increased by DNA damage. Furthermore, SUMO-modified Rad4 accumulated in NER
      mutants that block the pathway downstream of Rad4, suggesting that SUMO becomes
      attached to Rad4 at a specific point during its functional cycle. Collectively,
      these results suggest that SIZ-dependent sumoylation may modulate the activity of
      multiple proteins to promote efficient NER.

PMID- 21968060
TI  - Cytotoxic taraxerane triterpenoids from Saussurea graminea.
AB  - Four new taraxerane triterpenoids, 1beta,3beta-dihydroxy-11alpha,12alpha
      oxidotaraxerane (1), 28-hydroxy-11alpha,12alpha-oxidotaraxerane-3-one (2), 3beta
      hydroxy-11alpha,12alpha-oxidotaraxerane-28-al (3), and 3-O-acetyl-11alpha,12alpha
      oxidotaraxerane-28-al (4), together with three known compounds 3beta-hydroxy
      11alpha,12alpha-oxidotaraxerane (5), 3beta,28-dihydroxy-11alpha,12alpha
      oxidotaraxerane (6), and 11alpha,12alpha-oxidotaraxerane-3-one (7), were isolated
      from the 70% EtOH extract of Saussurea graminea. Their structures were elucidated
      on the basis of extensive 1D and 2D NMR (COSY, HMQC, HMBC and NOESY) analyses.
      The isolated compounds were evaluated in vitro for cytotoxic properties against
      eight tumor cell lines (A-549, BGC-823, HCT15, HeLa, HepG2, MCF-7, SGC-7901 and
      SK-MEL-2).

PMID- 21968061
TI  - Antioxidant flavonoids from Epimedium wushanense.
AB  - Two new flavonoids, wushanicaritin (1) and wushankaempferol (2), along with 24
      known flavonoids were isolated from the whole herb of Epimedium wushanense T.S.
      Ying (Berberidaceae). On the basis of NMR and ESI-MS spectroscopic analysis,
      structures of compounds 1 and 2 were elucidated as 8-gamma-hydroxy-gamma,gamma
      dimethylpropyl-3,5,7-trihydroxy-4'- methoxyflavone and kaempferol 3-O-alpha-l
      [2,3-di-O-beta-D-(6-E-p-coumaroyl) glucopyranosyl]-rhamnopyranosyl-7-O-alpha-L
      rhamnopyranoside, respectively. DPPH radical scavenging activity tests indicated
      that 1 (IC(50) 35.3 MUM) exhibited antioxidant activity comparable to Vitamin C
      (IC(50) 32.0 MUM), while 2 (IC(50) 443.7 MUM) showed weak activity.

PMID- 21968062
TI  - Cytotoxicity and antihyperglycemic effect of minor constituents from Rhizoma
      Coptis in HepG2 cells.
AB  - Generally, berberine, coptisine, palmatine, and jatrorrhizine were considered as
      the main bio-active compounds in Rhizoma Coptis (RC). Little attention was paid
      to investigate the pharmacological activity of minor constituents in RC. The
      present study was designed to separate the minor compounds, and the cytotoxicity
      and antihyperglycemic effect of these compounds in HepG2 cells were also studied.
      Palmatine (1), berberine (2), coptisine (3), epiberberine (4), columbamine (5),
      and jatrorrhizine (6) from RC ethanol extract were isolated by high speed counter
      current chromatography (HSCCC) in one run. The remaining fraction (about 50% of
      extract in HSCCC) was further isolated by traditional column chromatography
      methods to yield magnoflorine (7), ferulic acid (8), and choline (9). Another
      four alkaloids, namely groenlandicine (10), berberrubine (11), oxyberberine (12),
      8-oxo-coptisine (13), also were obtained from CHCl(3) extracts. Especially,
      choline was first isolated from RC. Cell assay indicated that the minor fractions
      excluding compounds 1-6 showed obvious glucose lowering activity. In addition,
      the minor monomers also exhibited moderate glucose lowering activity. The
      combination of berberine and ferulic acid showed synergistic effect on
      antihyperglycemic. The combination of alkaloids 1-6 was same so. All compounds
      had different cytotoxicity in HepG2 cells within the test concentration. Of them,
      berberrubine showed the strongest cytotoxicity. The results suggested that
      combined action of variety constituents contributed to the antihyperglycemic
      effects and low cytotoxicity of RC extract in HepG2 cells.

PMID- 21968063
TI  - Sesquiterpenoids and norterpenoids from Vitex negundo.
AB  - Chemical investigation on the seeds of Vitex negundo has afforded a new furan
      containing sesquiterpenoid, negunfurol (1), a new norlabdane-type diterpenoid,
      negundoal (2), and two new norursane-type triterpenoids, negundonorins A (3) and
      B (4), together with two know compounds, 3-formyl-4,5-dimethyl-8-oxo-5H-6,7
      dihydronaphtho[2,3-b]furan (5) and 3-epi-corosolic acid (6). Their structures and
      configurations were elucidated by detailed spectroscopic analyses on the basis of
      NMR, IR, and MS data. Compound 3 was strongly cytotoxic against ZR-75-30 cell
      line with IC(50) value of 0.56 +/- 0.19 MUg/mL, whereas compound 1 was most
      active against HL-60 cell line with IC(50) value of 0.94 +/- 0.26 MUg/mL.

PMID- 21968064
TI  - Evaluation of analgesic, anti-inflammatory and hepatoprotective effects of
      lycorine from Sternbergia fisheriana (Herbert) Rupr.
AB  - The present study reports the potential antinociceptive, anti-inflammatory and
      hepatoprotective activities of lycorine from Sternbergia fischeriana (Herbert)
      Rupr. (Amaryllidaceae). Lycorine was evaluated on mice by using acetic-acid
      induced writhing and tail-flick tests. Lycorine exhibited stronger inhibition
      than aspirin in acetic-acid induced abdominal stretching at 1.0mg/kg dose.
      Lycorine also showed antinociceptive activity at 1.0mg/kg dose in tail-flick
      test. The anti-inflammatory activity of lycorine was not found to be significant
      at dose of 0.5mg/kg. However, at doses of 1.0mg/kg and 1.5mg/kg, i.p. showed a
      significant reduction with 53.45% and 36.42%, respectively in rat paw oedema
      induced by carrageenan against the reference anti-inflammatory drug indomethacin
      (3mg/kg, i.p.) (95.70%). The ED(50) of lycorine was determined as 0.514 mg/kg.
      Hepatoprotective activity of lycorine on carbon tetrachloride (CCl(4)) induced
      acute liver toxicity following biochemical parameters were also evaluated. Rats
      were treated with lycorine at doses of 1.0mg/kg and 2.0mg/kg, i.p. Results of
      biochemical tests were confirmed by histopathological examination. Lycorine
      exhibited significant hepatoprotective effect at dose of 2.0mg/kg i.p. dose.

PMID- 21968065
TI  - Antinociceptive and antiplasmodial activities of cassane furanoditerpenes from
      Caesalpinia volkensii H. root bark.
AB  - The chloroform and ethyl acetate extract (100mg/kg) of Caesalpinia volkensii H.
      exhibited significant (P <= 0.05) antinociceptive activities using hot plate and
      writhing tests in mice while the later showed antiplasmodial activity (IC(50)
      0.23 +/- 0.07 and 4.39 +/- 2.49 MUg/ml) against chloroquine sensitive (D6) and
      chloroquine-resistant (W2), respectively. Two new furanoditerpenes [rel.
      1beta,5alpha-dihydroxyvoucapane (1) and rel. 1beta,6beta-dihydroxyvoucapane;
      19beta-methyl ester (2)] together with seven known compounds [voucapane (3),
      voucapan-5-ol (4), deoxycaesaldekarin C (5), caesaldekarin C (6), 5
      hydroxyvinhaticoic acid (7), triacontanyl-(E)-ferulate (8), triacontanyl-(E)
      caffaete (9) and 30'-hydroxytriacontanyl-(E)-ferulate (10)] were isolated from
      the two extracts. The administration of 3, 4, 5 and 6 (100mg/kg i.p) caused a
      significant (P <= 0.05) reduction in the number of writhing episodes induced by
      acetic acid and (P <= 0.01) increased pain latency threshold in hot-plate test
      compared to control. However, the pure compounds indicated relatively (P <= 0.05)
      low antiplasmodial activity. The phytochemical constituents from the root bark of
      C. volkensii had better analgesic properties than antimalarial properties,
      justifying the use of the plant root bark as a remedy for pain.

PMID- 21968066
TI  - Improved field emission performance of carbon nanotube by introducing copper
      metallic particles.
AB  - To improve the field emission performance of carbon nanotubes (CNTs), a simple
      and low-cost method was adopted in this article. We introduced copper particles
      for decorating the CNTs so as to form copper particle-CNT composites. The
      composites were fabricated by electrophoretic deposition technique which produced
      copper metallic particles localized on the outer wall of CNTs and deposited them
      onto indium tin oxide (ITO) electrode. The results showed that the conductivity
      increased from 10-5 to 4 * 10-5 S while the turn-on field was reduced from 3.4 to
      2.2 V/MUm. Moreover, the field emission current tended to be undiminished after
      continuous emission for 24 h. The reasons were summarized that introducing copper
      metallic particles to decorate CNTs could increase the surface roughness of the
      CNTs which was beneficial to field emission, restrain field emission current from
      saturating when the applied electric field was above the critical field. In
      addition, it could also improve the electrical contact by increasing the contact
      area between CNT and ITO electrode that was beneficial to the electron transport
      and avoided instable electron emission caused by thermal injury of CNTs.

PMID- 21968067
TI  - Development of an assay of seven biochemical items, HbA1c, and hematocrit using a
      small amount of blood collected from the fingertip.
AB  - BACKGROUND: Lifestyle-related diseases in Japan account for 30% of the entire
      medical expenditure of the country and cause 60% of all deaths. For the
      prevention of lifestyle-related diseases, medical examination by laboratory tests
      on metabolic syndrome is important. METHODS: To undertake examination by
      collection of blood from a fingertip, we developed the "Well Kit". About 65 MUl
      of blood collected from a fingertip was diluted with buffer solution, which
      contained two internal standard materials. The kit also separated corpuscles and
      diluted plasma with a special filter. It measured the obtained diluted plasma
      using the JCA-BM2250. RESULTS: This measurement system was evaluated for the
      quantitative analysis of 8 items. The uncertainties of tested items of this
      measurement system were 1.7% to 6.4%. The coefficients of correlation of all
      tested items between this measurement value and the venous plasma sample value
      were 0.876-0.991, and hematocrit was 0.958. CONCLUSIONS: This system for testing
      blood collected from a fingertip is simple to use and can be applied in testing
      for metabolic syndrome. In addition, this testing system is useful in the medical
      examination of the personal healthcare and inhabitants.

PMID- 21968068
TI  - TRPC1 proteins confer PKC and phosphoinositol activation on native heteromeric
      TRPC1/C5 channels in vascular smooth muscle: comparative study of wild-type and
      TRPC1-/- mice.
AB  - Ca(2+)-permeable cation channels consisting of canonical transient receptor
      potential 1 (TRPC1) proteins mediate Ca(2+) influx pathways in vascular smooth
      muscle cells (VSMCs), which regulate physiological and pathological functions. We
      investigated properties conferred by TRPC1 proteins to native single TRPC
      channels in acutely isolated mesenteric artery VSMCs from wild-type (WT) and
      TRPC1-deficient (TRPC1(-/-)) mice using patch-clamp techniques. In WT VSMCs, the
      intracellular Ca(2+) store-depleting agents cyclopiazonic acid (CPA) and 1,2-bis
      (2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM) both evoked channel
      currents, which had unitary conductances of ~2 pS. In TRPC1(-/-) VSMCs, CPA
      induced channel currents had 3 subconductance states of 14, 32, and 53 pS.
      Passive depletion of intracellular Ca(2+) stores activated whole-cell cation
      currents in WT but not TRPC1(-/-) VSMCs. Differential blocking actions of anti
      TRPC antibodies and coimmunoprecipitation studies revealed that CPA induced
      heteromeric TRPC1/C5 channels in WT VSMCs and TRPC5 channels in TRPC1(-/-) VSMCs.
      CPA-evoked TRPC1/C5 channel activity was prevented by the protein kinase C (PKC)
      inhibitor chelerythrine. In addition, the PKC activator phorbol 12,13-dibutyrate
      (PDBu), a PKC catalytic subunit, and phosphatidylinositol-4,5-bisphosphate
      (PIP(2)) and phosphatidylinositol-3,4,5-trisphosphate (PIP(3)) activated TRPC1/C5
      channel activity, which was prevented by chelerythrine. In contrast, CPA-evoked
      TRPC5 channel activity was potentiated by chelerythrine, and inhibited by PDBu,
      PIP(2), and PIP(3). TRPC5 channels in TRPC1(-/-) VSMCs were activated by
      increasing intracellular Ca(2+) concentrations ([Ca(2+)](i)), whereas increasing
      [Ca(2+)](i) had no effect in WT VSMCs. We conclude that agents that deplete
      intracellular Ca(2+) stores activate native heteromeric TRPC1/C5 channels in
      VSMCs, and that TRPC1 subunits are important in determining unitary conductance
      and conferring channel activation by PKC, PIP(2), and PIP(3).

PMID- 21968069
TI  - Involvement of aquaporin-7 in the cutaneous primary immune response through
      modulation of antigen uptake and migration in dendritic cells.
AB  - Dendritic cells (DCs) have the ability to present antigen and play a critical
      role in the induction of the acquired immune response. Skin DCs uptake antigen
      and subsequently migrate to regional draining lymph nodes (LNs), where they
      activate naive T cells. Here we show that the water/glycerol channel protein
      aquaporin 7 (AQP7) is expressed on epidermal and dermal DCs and involved in the
      initiation of primary immune responses. AQP7-deficient DCs showed a decreased
      cellular uptake of low-molecular-mass compounds (fluorescein isothiocyanate and
      Lucifer yellow) and high-molecular-mass substances (ovalbumin and dextran),
      suggesting that AQP7 is involved in antigen uptake. AQP7-deficient DCs also
      exhibited reduced chemokine-dependent cell migration in comparison to wild-type
      DCs. Consistent with these in vitro results, AQP7-deficient mice demonstrated a
      reduced accumulation of antigen-retaining DCs in the LNs after antigen
      application to the skin, which could be attributed to decreased antigen uptake
      and migration. Coincidentally, AQP7-deficient mice had impaired antigen-induced
      sensitization in a contact hypersensitivity model. These observations suggested
      that AQP7 in skin DCs is primarily involved in antigen uptake and in the
      subsequent migration of DCs and is responsible for antigen presentation and the
      promotion of downstream immune responses.

PMID- 21968070
TI  - Polyunsaturated fatty acids are incorporated into maturating male mouse germ
      cells by lysophosphatidic acid acyltransferase 3.
AB  - Long-chain polyunsaturated fatty acids (PUFAs) accumulate in mammalian testis
      during puberty and are essential for fertility. To investigate whether
      lysophospholipid acyltransferases determine the PUFA composition of testicular
      phospholipids during pubertal development, we compared their mRNA expression, in
      vitro activity, and specificity with the lipidomic profile of major
      phospholipids. The accumulation of PUFAs in phosphatidylcholine,
      phosphatidylethanolamine, and phosphatidylserine correlated with an induced
      lysophosphatidic acid acyltransferase (LPAAT)3 mRNA expression, increased
      microsomal LPAAT3 activity, and shift of LPAAT specificity to PUFA-coenzyme A.
      LPAAT3 was induced during germ cell maturation, as shown by immunofluorescence
      microscopy. Accordingly, differentiation of mouse GC-2spd(ts) spermatocytes into
      spermatides up-regulated LPAAT3 mRNA, increased the amount of polyunsaturated
      phospholipids, and shifted the specificity for the incorporation of deuterium
      labeled docosahexaenoic acid toward phosphatidylcholine and
      phosphatidylethanolamine. Stable knockdown of LPAAT3 in GC-2spd(ts) cells
      significantly decreased microsomal LPAAT3 activity, reduced levels of
      polyunsaturated phosphatidylethanolamine species, and impaired cell
      proliferation/survival during geneticin selection. We conclude that the induction
      of LPAAT3 during germ cell development critically contributes to the accumulation
      of PUFAs in testicular phospholipids, thereby possibly affecting sperm cell
      production.

PMID- 21968071
TI  - Sutureless valve implantation in a patient with bicuspid aortic valve.

PMID- 21968072
TI  - Identifying elderly patients with advanced heart failure at the end of life.

PMID- 21968073
TI  - Clinical outcomes following a strategy of optimized medical management and
      selective "downstream" procedures following coronary computed tomography
      angiography.
AB  - BACKGROUND: Prior studies have shown a consistent relationship between coronary
      artery calcium (CAC) scores or the degree of coronary stenoses on coronary
      computed tomography angiography (CCTA) and all-cause mortality. Whether CCTA
      targeted therapy, including intensive medical management, stress testing and/or
      invasive coronary angiography (ICA), can lead to a substantial reduction in
      adverse outcomes is not yet known. METHODS: We retrospectively analyzed 691
      patients (55+/-13 years, male=63%) from a single medical practice who underwent a
      CAC scan and CCTA and were followed for a mean of 2.9+/-1.0 years. Of these, 416
      (60%) patients were asymptomatic. All changes in medications, coronary risk
      factors (including lipids profiles), downstream testing, revascularization
      procedures, and clinical events (myocardial infarction and death) were recorded.
      RESULTS: Among our patients cohort 279 (40%) had no coronary artery disease. The
      most severe stenosis was <50% in 314 (46%) patients, 50-70% in 76 (11%) patients,
      and >70% in 22 (3%) patients. A high frequency of medical therapy was employed
      for those patients with any degree of stenosis, while stress testing was
      primarily applied for patients with >50% stenosis and ICA was primarily performed
      in those with >70% stenosis. Only two non-cardiovascular deaths and no
      cardiovascular deaths occurred during the follow-up period. CONCLUSIONS: Our
      findings support the hypotheses that among patients undergoing CCTA,
      comprehensive medical management, including targeted percutaneous coronary
      interventions and increasingly intensive medical therapy with progressively worse
      CCTA findings, can reduce event rates among patients with abnormal CCTA studies.

PMID- 21968074
TI  - p2PSA but not total and free PSA increases after myocardial infarction: results
      of a preliminary investigation.

PMID- 21968075
TI  - Admission time, variability in clinical characteristics, and in-hospital outcomes
      in acute heart failure syndromes: findings from the ATTEND registry.

PMID- 21968076
TI  - C-reactive protein and particulate matter predict plasma fibrinogen levels.

PMID- 21968077
TI  - Aspirin intolerance and the need for dual antiplatelet therapy after stent
      implantation: a proposed alternative regimen.
AB  - BACKGROUND: Dual antiplatelet therapy (DAT, i.e. aspirin+thienopyridine) has been
      shown to reduce the risk of stent thrombosis (ST) and myocardial infarction (MI)
      after coronary stent implantation. Data regarding alternative antiplatelet
      therapy in patients with allergy or intolerance to aspirin are lacking. METHODS:
      This study is a retrospective analysis of consecutive patients with adverse
      reactions to aspirin who received an alternative combination of DAT (indobufen,
      trapidil, or triflusal in association with a thienopyridine) after elective
      implantation of either drug-eluting (DES) or bare-metal stents (BMS). Endpoints
      analyzed were cardiac death, MI, ST and bleeding. RESULTS: A total of 127
      patients undergoing stenting of 267 lesions (DES 84%, BMS 16%), were identified
      between June'99 and November'08. Reasons for not taking aspirin included
      gastrointestinal intolerance (53.5%), allergy (39.4%), non-gastrointestinal
      bleeding (5.5%) and others (1.6%). Aspirin was substituted with indobufen
      (64.6%), trapidil (26.8%), triflusal (6.3%), or a combination of
      indobufen+trapidil (2.4%). Median duration of DAT was 369 days [IQR 273-1053]
      after DES and 46.5 days [IQR 30-699] after BMS implantation. Only 3.1% of
      patients prematurely discontinued DAT. During a median follow-up of 1161 days
      [IQR 781-1538], rates of cardiac death and MI were 3.1% and minor bleeding
      occurred in 1.5%. There was 1 very late definite ST occurring 2 days after DAT
      discontinuation and no probable ST. CONCLUSIONS: In this cohort of patients with
      aspirin intolerance undergoing coronary stent implantation, the combination of a
      thienopyridine with indobufen, trapidil, or triflusal was associated with a low
      rate of cardiac death, ST and MI.

PMID- 21968078
TI  - Influence of glutathione S-transferase T1 donor/recipient mismatch and anti-GSTT1
      antibodies in hepatic graft-versus-host-disease.
AB  - B cell responses to minor histocompatibility antigens (mHags) have not been
      extensively studied after allogeneic hematopoietic stem cell transplantation
      (HSCT). Glutathione S-transferase T1 (GSTT1) is a drug metabolizing enzyme
      encoded by a single gene that is highly expressed in liver and kidney. Anti-GSTT1
      antibodies have been described in the context of antibody-mediated rejection in
      kidney and liver transplantation, due to a mismatch between donor and recipient.
      The aim of the present study was to investigate the specific immune response
      against GSTT1 in HSCT with production of antibodies and their influence in the
      development of hepatic graft-versus-host-disease (GVHD). Forty patients and their
      respective donors were included in the study. The median follow-up time was 35.6
      months (range 0.6-76 months) and a total of 349 serum samples were tested for the
      presence of anti-GSTT1 antibodies by ELISA test. Statistical analysis was
      performed by defining the GSTT1 null donor/positive recipient as mismatch
      compared with the other three genetic combinations regarded as GSTT1-matched.
      Antibodies were found in three patients within the group of null donor/positive
      recipient and one within the null/null group. Development of liver GVHD,
      particularly its acute form, was highly associated with the GSTT1-mismatch
      (P=0.0178) and with the presence of post-transplant anti-GSTT1 antibodies
      (P=0.0076). We conclude that GSTT1 could be considered as a new mHag in hepatic
      GVHD. The fact that three donors were parous females and the rapid production of
      antibodies after HSCT suggests the existence in the graft of memory B-cells
      specific for the GSTT1 antigen.

PMID- 21968079
TI  - Framing the social in biomedical HIV prevention trials: a 20-year retrospective.
AB  - Biomedical research is critical to identifying effective and safe interventions,
      such as vaccines, microbicides, male circumcision and antiretrovirals, for
      prevention. Funding for clinical prevention trials is highly competitive and the
      benchmarks of success ultimately reduce to quickly enrolling a select group of
      people at risk, keeping them enrolled, and inducing them to be compliant with
      trial requirements - all at the lowest cost possible. Juxtaposed with this
      reality is the fact that HIV is situated with poverty, exploitation, assaults on
      human dignity, and human rights abuses. The result is a complex web of ethical
      challenges that are socially constructed along lines of wealth and power. While
      social science research methods are commonly employed to examine such topics,
      they have played a marginal role in biomedical HIV prevention research. Why? To
      answer this question, a core set of persistent interlocking social, behavioural
      and ethical challenges to biomedical HIV prevention research are described. A
      critique is offered on how the social has been framed relative to the
      behavioural, ethical and biomedical components. Examples of how this framing has
      devalued social knowledge are provided, including the conflation of qualitative
      research with anecdotal reporting, a bias toward brevity and accuracy over
      external validity, and difficulties in distinguishing between a moral
      understanding of social norms and achieving a moral outcome when confronted with
      ethical challenges in research. Lastly, opportunities are identified for
      enhancing the success of biomedical HIV prevention research through development
      of a coherent programme of social science research. Recommendations are offered
      for reframing the social as a valid domain of scientific inquiry in this highly
      applied and interdisciplinary context.

PMID- 21968080
TI  - Persistent negative symptoms in first-episode schizophrenia: a prospective three
      year follow-up study.
AB  - BACKGROUND: Negative symptoms are a core feature of schizophrenia. The evolution
      and trajectory of primary negative symptoms were under-studied. We aimed at
      evaluating the prevalence and stability of primary negative symptoms, and factors
      associated with persistent primary negative symptoms in a first-episode sample.
      METHOD: Ninety-three Hong Kong Chinese aged 18 to 55 years presenting with first
      episode schizophrenia-spectrum disorder were studied. Data on premorbid
      adjustment, socio-demographics, and baseline clinical and cognitive profiles were
      obtained. Psychopathological and vocational reassessments were conducted at 12,
      24 and 36 months. Primary negative symptoms were defined as the presence of
      clinically significant negative symptoms excluding depression and extra-pyramidal
      signs. RESULTS: At baseline, 25.8% of subjects exhibited primary negative
      symptoms. A quarter of patients had their initial primary negative symptoms
      status retained 12 months after treatment initiation. In both Year 2 and Year 3
      of study period, around 70% of subjects had their primary negative symptoms
      status maintained for 12 months. At the end of three-year follow-up, 23.7% were
      categorized as having persistent primary negative symptoms. Male sex,
      unemployment at intake, prolonged duration of untreated psychosis, poorer
      premorbid academic and social functioning, poorer insight and worse vocational
      outcome were found to be associated with persistent primary negative symptoms.
      CONCLUSION: Clinical status of primary negative symptoms in first-episode
      schizophrenia-spectrum disorder was unstable in the initial year of treatment.
      Baseline symptom assessment may not reliably predict development of persistent
      primary negative symptoms. Studying negative symptoms should take into account
      the longitudinal perspective, especially in the early course of psychotic
      disorders.

PMID- 21968082
TI  - Metastatic ameloblastoma responding to combination chemotherapy: case report and
      review of the literature.
AB  - BACKGROUND: Ameloblastoma is a rare benign odontogenic tumor with locally
      aggressive behavior and a high recurrence rate. When metastases occur, which are
      uncommon, lungs constitute the most frequent site involved. Malignant
      ameloblastomas are different from ameloblastic carcinomas. Malignant
      ameloblastomas are tumors considered metastatic despite the appearance of well
      differentiated or benign histology, while ameloblastic carcinomas are
      histologically malignant in both primary and metastatic sites. CASE PRESENTATION:
      A 24-year-old Moroccan man presented a malignant ameloblastoma of the mandible.
      The tumor was entirely resected. Five years later, a local recurrence occurred.
      Our patient was treated by exclusive radiotherapy with persistence of a residual
      disease. After two years he developed multiple lung metastases. Our patient
      received a combination chemotherapy using doxorubicin and cisplatin. CONCLUSION:
      Less than 50 cases of ameloblastoma with metastases have been reported. There is
      still no standard treatment for metastatic ameloblastoma. Only through continuous
      reporting of such cases will clinicians be able to draw an optimal strategy for
      management of this pathology.

PMID- 21968081
TI  - Some behavioral and neurobiological constraints on theories of audiovisual speech
      integration: a review and suggestions for new directions.
AB  - Summerfield (1987) proposed several accounts of audiovisual speech perception, a
      field of research that has burgeoned in recent years. The proposed accounts
      included the integration of discrete phonetic features, vectors describing the
      values of independent acoustical and optical parameters,  the filter function of
      the vocal tract, and articulatory dynamics of the vocal tract. The latter two
      accounts assume that the representations of audiovisual speech perception are
      based on abstract gestures, while the former two assume that the representations
      consist of symbolic or featural  information obtained from visual and auditory
      modalities. Recent converging evidence from several different disciplines reveals
      that the general framework of Summerfield's feature-based theories should be
      expanded. An updated framework building upon the feature-based theories is
      presented.  We propose a processing model arguing that auditory and visual brain
      circuits provide facilitatory information when the inputs are correctly timed,
      and that auditory and visual speech representations do not necessarily undergo
      translation into a common code during information processing. Future  research on
      multisensory processing in speech perception should investigate the connections
      between auditory and visual brain regions, and utilize dynamic modeling tools to
      further understand the timing and information processing mechanisms involved in
      audiovisual speech integration.

PMID- 21968083
TI  - Comparison of nickel silicide and aluminium ohmic contact metallizations for low
      temperature quantum transport measurements.
AB  - We examine nickel silicide as a viable ohmic contact metallization for low
      temperature, low-magnetic-field transport measurements of atomic-scale devices in
      silicon. In particular, we compare a nickel silicide metallization with
      aluminium, a common ohmic contact for silicon devices. Nickel silicide can be
      formed at the low temperatures (<400 degrees C) required for maintaining atomic
      precision placement in donor-based devices, and it avoids the complications found
      with aluminium contacts which become superconducting at cryogenic measurement
      temperatures. Importantly, we show that the use of nickel silicide as an ohmic
      contact at low temperatures does not affect the thermal equilibration of carriers
      nor contribute to hysteresis in a magnetic field.

PMID- 21968084
TI  - Simvastatin induces the expression of hemeoxygenase-1 against ischemia
      reperfusion injury on the testes in rats.
AB  - We evaluate the protective role of simvastatin-induced HO-1 in remote
      preconditioning against testis ischemia-reperfusion (IR) injury in vivo.
      Simvastatin was intraperitoneally (i.p.) injected 24 h before IR injury. Testis
      was occluded in the right testis for 40 min and followed by 30 min of reperfusion
      to induce IR injury. Tin protoporphyrin (Snpp), a competitive inhibitor of
      hemeoxygenase, was i.p. injected 1 h before the IR injury in separate groups of
      rats. The rat testes were harvested 24 h later. Induction of HO-1 expression by
      simvastatin was significantly increased at 24 and 48 h. Rats pre-treated with
      simvastatin showed higher expression of HO-1 protein by Western blotting and
      immunohistochemistry (IHC), and presented lower caspases-3 activity by caspase-3
      activity assay. TUNEL staining analysis revealed simvastatin pretreatment
      significantly reduced IR induced cellular apoptosis. Contrarily, the simvastatin
      induced cytoprotective effect was entirely abolished by administrations of Snpp.
      Further, lower caspase-3 activities were also noted in simvastatin plus Snpp (SS)
      group than the control plus Snpp (CS) group. After IR injury, eNOS
      immunoreactivity was markedly increased in the germ cell and Leydig cell of
      testicular tissues. Pretreatment of simvastatin significantly decreased eNOS
      immunoreactivity in the germ cell of the tubules in the rat testes. In
      conclusion, we suggest HO-1 plays a protective role in IR-induced injury in the
      testes of rats.

PMID- 21968085
TI  - Hypothesis: Cystic fibrosis carrier geography reflects interactions of
      tuberculosis and hypertension with vitamin D deficiency, altitude and
      temperature. Vitamin D deficiency effects and CF carrier advantage.
AB  - Interactions between selective factors (hypertension and tuberculosis) and
      environmental effects (vitamin D deficiency [VDD], temperature, and altitude)
      largely explain cystic fibrosis (CF) carrier geography. For VDD sequelae such as
      hypertension and tuberculosis vulnerability, clinical evidence of carrier
      protection is supported by indications that decreased CF arylsulfatase B activity
      suppresses tuberculosis, and that excess CF salt loss decreases blood pressure. A
      need for salt retention in the tropics selected against CF carriers despite
      possible advantages against cholera, typhoid, and other factors, but salt
      retention was less important elsewhere. Increased hypertension with cold selected
      for carriers with increasing latitude, and with altitude, where hypertensive
      complications of pregnancy also rise. DeltaF508 rates especially seem to follow
      these parameters, and may be particularly protective against hypertension, while
      lower rates in Ashkenazi Jews are consistent with a greater role for tuberculosis
      in this group. This scenario suggests geographical correlations of CF with other
      genes affecting blood pressure, and significant carrier levels, especially of
      DeltaF508, in mountainous areas of Asia with VDD.

PMID- 21968086
TI  - MALDI-TOF MS improves routine identification of non-fermenting Gram negative
      isolates from cystic fibrosis patients.
AB  - Identification of non-fermenting Gram-negative bacteria (NFGNB) from cystic
      fibrosis (CF) patients is often limited. A collection of stored NFGNB isolates
      (n=182) recovered from CF patients over a 15 year period was examined. The
      routinely reported identification during this period was compared with that
      obtained by MALDI-TOF MS. Isolates giving discrepant identification at the genus
      level were further analyzed by 16S rDNA sequencing. The MALDI-TOF MS system
      identified 94% of the isolates, including Burkholderia cepacia and Pandoraea spp.
      isolates, the latter previously misidentified as other NFGNB by conventional
      microbiological methods. Lack of identification by MALDI-TOF MS was associated
      with the absence of entries in the database.

PMID- 21968087
TI  - The prevalence of "risky behaviour" in adults with cystic fibrosis.
AB  - BACKGROUND: The prevalence of "risky-behaviour" including alcohol and illicit
      drug use, smoking and unprotected sexual intercourse, of adults with cystic
      fibrosis (CF) is unknown. We conducted this prospective questionnaire-based study
      to further explore this issue. METHODS: An anonymous 71-point questionnaire was
      sent to all adult patients aged >=18 years attending the Royal Brompton CF Unit.
      Results were compared to national (non-CF) data. RESULTS: 83% (n=151) drink
      alcohol and 13% (n=23) drink more than recommended by national guidelines. 46%
      (n=84) have tried smoking and 3% (n=5) continue to smoke regularly. 35% (n=64)
      have tried illicit drugs and 3% (n=6) continue to use them. 86% (n=154) are
      sexually active; 60% use contraception (males 46%, females 62%). Compared with
      the general (non-CF) UK population, less CF patients drink heavily (13 vs. 23%;
      p<0.001), smoke (3 vs. 21%; p<0.001), have tried illicit drugs (35 vs. 37%;
      p<0.001) and are sexually active (86 vs. 97%; p<0.001).The same proportion use
      contraception (60 vs. 61%; p=0.8). CONCLUSION: Participation in risky behaviour
      was modest. With improved life expectancy this may increase. Awareness of this is
      important so that health promotion measures can be introduced early.

PMID- 21968088
TI  - Together we can make a difference: the case for transnational action for improved
      health in prisons.
AB  - In spite of international differences in the treatment of incarcerated persons,
      as a group, they are vulnerable to poor health status and lack of access to
      quality health care. The health care of prisoners is affected by knowledge and
      commitment to ideas of human rights and social justice, as well as economic
      conditions. Prisoners are at increased risk of both acute and chronic diseases,
      and may constitute a threat to the health of other prisoners, their attendants or
      outside communities upon release. Mental illness and related problems of
      substance abuse are prevalent in prison populations, with many US prisons serving
      as modern asylums. Public health workers and organizations can stimulate and
      implement action to improve health in prisons. The World Federation of Public
      Health Associations can play a leadership role in co-ordinating and facilitating
      collaborative international action and research to enhance the health of
      prisoners and their communities worldwide.

PMID- 21968089
TI  - Utilizing qualitative methods in survey design: examining Texas cattle producers'
      intent to participate in foot-and-mouth disease detection and control.
AB  - The effective control of an outbreak of a highly contagious disease such as foot
      and-mouth disease (FMD) in the United States will require a strong partnership
      between the animal agriculture industry and the government. However, because of
      the diverse number of economic, social, and psychological influences affecting
      livestock producers, their complete cooperation during an outbreak may not be
      assured. We conducted interviews with 40 individuals involved in the Texas cattle
      industry in order to identify specific behaviors where producer participation or
      compliance may be reduced. Through qualitative analysis of these interviews, we
      identified specific factors which the participants suggested would influence
      producer behavior in regard to FMD detection and control. Using the Theory of
      Planned Behavior (TPB) as an initial guide, we developed an expanded theoretical
      framework in order to allow for the development of a questionnaire and further
      evaluation of the relative importance of the relationships indicated in the
      framework. A 2-day stakeholder workshop was used to develop and critique the
      final survey instruments. The behaviors which we identified where producer
      compliance may be reduced included requesting veterinary examination of cattle
      with clinical signs of FMD either before or during an outbreak of FMD, gathering
      and holding cattle at the date and time requested by veterinary authorities, and
      maintaining cattle in their current location during an outbreak of FMD. In
      addition, we identified additional factors which may influence producers'
      behavior including risk perception, trust in other producers and regulatory
      agencies, and moral norms. The theoretical frameworks presented in this paper can
      be used during an outbreak to assess barriers to and social pressures for
      producer compliance, prioritize the results in terms of their effects on
      behavior, and improve and better target risk communication strategies.

PMID- 21968090
TI  - Salivary gland carcinoma in Denmark 1990-2005: outcome and prognostic factors.
      Results of the Danish Head and Neck Cancer Group (DAHANCA).
AB  - To describe outcome and prognostic factors in a national Danish series of
      patients treated for salivary gland carcinoma. From three Danish nation-wide
      registries and supplementary patient records, 871 patients diagnosed with primary
      major or minor salivary gland carcinoma in the period from 1990 to 2005 were
      identified. A total of 796 (91%) histological specimens were revised according to
      the WHO 2005 classification. The median follow-up time was 78 months. Three
      hundred and thirty-four patients (38%) experienced recurrence. Crude survival,
      disease-specific survival and recurrence-free survival after 5 and 10 years were
      66%, 76%, 64% and 51%, 69%, 58%, respectively. In multivariate analysis age,
      latency, stage, microscopic margins, vascular invasion and histological grade
      were all independent prognostic factors with regards to crude and disease
      specific survival. Stage, microscopic margins, vascular invasion and histological
      grade were independent prognostic factors for recurrence-free survival. Age over
      61 years, latency under 8 months, stage 3+4 disease, involved or close
      microscopic margins, vascular invasion and high histological grade are all
      independent prognostic factors with a negative impact on survival in salivary
      gland carcinoma patients. This knowledge can be helpful in guiding clinicians in
      daily work and choice of treatment across the large variety of salivary gland
      carcinoma subtypes.

PMID- 21968091
TI  - Critically engaging: integrating the social and the biomedical in international
      microbicides research.
AB  - Randomized controlled trials and critical social theory are known not to be happy
      bedfellows. Such trials are embedded in a positivist view of the world, seeking
      definitive answers to testable questions; critical social theory questions the
      methods by which we deem the world knowable and may consider experiments in the
      biomedical sciences as social artifacts. Yet both of these epistemologically and
      methodologically divergent fields offer potentially important advances in HIV
      research. In this paper, we describe collaboration between social and biomedical
      researchers on a large, publicly funded programme to develop vaginal microbicides
      for HIV prevention. In terms of critical engagement, having integrated and
      qualitative social science components in the protocol meant potentially nesting
      alternative epistemologies at the heart of the randomized controlled trial. The
      social science research highlighted the fallibility and fragility of trial data
      by demonstrating inconsistencies in key behavioural measurements. It also
      foregrounded the disjuncture between biomedical conceptions of microbicides and
      the meanings and uses of the study gel in the context of users' everyday lives.
      These findings were communicated to the clinical and epidemiological members of
      the team on an ongoing basis via a feedback loop, through which new issues of
      concern could also be debated and, in theory, data collection adjusted to the
      changing needs of the programme. Although critical findings were taken on board
      by the trialists, a hierarchy of evidence nonetheless remained that limited the
      utility of some social science findings. This was in spite of mutual respect
      between clinical epidemiologists and social scientists, equal representation in
      management and coordination bodies, and equity in funding for the different
      disciplines. We discuss the positive role that social science integrated into an
      HIV prevention trial can play, but nonetheless highlight tensions that remain
      where a hierarchy of epistemologies exists alongside competing paradigms and
      priorities.

PMID- 21968092
TI  - Tissue plasminogen activator thrombolytic therapy for acute ischemic stroke in 4
      hospital groups in Japan.
AB  - In October 2005 in Japan, the recombinant tissue plasminogen activator (tPA)
      alteplase was approved for patients with acute ischemic stroke within 3 hours of
      onset at a dose of 0.6 mg/kg. The present study was undertaken to assess the
      safety and efficacy of alteplase in Japan. Between October 2005 and December
      2009, a total of 114 consecutive patients admitted to 4 hospitals received
      intravenous tPA within 3 hours of stroke onset. Clinical backgrounds and outcomes
      were investigated. The patients were divided into 2 chronological groups: an
      early group, comprising 45 patients treated between October 2005 and December
      2007, and a later group, comprising 69 patients treated between January 2008 and
      December 2009. The mean time from arrival at the hospital to the initiation of
      treatment was significantly reduced in the later group, from 82.6 minutes to 70.9
      minutes. Intracerebral hemorrhage (ICH) occurred in 26 patients (22.8%); compared
      with patients without ICH, these patients had a significantly higher prevalence
      of cardiogenic embolism (88.5% vs 58.0%); greater warfarin use (26.8% vs 6.8%);
      higher mean National Institutes of Health Stroke Scale (NIHSS) scores on
      admission (16 vs 10), at 3 days after admission (14 vs 5), and at 7 days after
      admission (13.5 vs 3); and a lower Diffusion-Weighted Imaging-Alberta Stroke
      Program Early CT Score (7.8 vs 9.1). Patients who received edaravone had a higher
      prevalence of cardiogenic embolism (70.9% vs 36.4%), a higher recanalization rate
      (77.7% vs 36.4%), and lower NIHSS scores on admission and at 3 and 7 days after
      admission compared with those who did not receive edaravone. Our data suggest
      that administration of intravenous alteplase 0.6 mg/kg within 3 hours of stroke
      onset is safe and effective, that the NIHSS and Diffusion-Weighted Imaging
      Alberta Stroke Program Early CT Score are useful predictors of ICH after tPA
      administration, and that warfarin-treated patients are more likely to develop
      symptomatic ICH despite an International Normalized Ratio <1.7.

PMID- 21968093
TI  - Swallowing analysis for semisolid food texture in poststroke dysphagic patients.
AB  - BACKGROUND: Our objective was to determine the texture of semisolid foods that
      are appropriate for poststroke dysphagic patients. METHODS: Subjects included 52
      poststroke dysphagic patients (72 +/- 8 years of age) who were trained with
      semisolid foods and required the evaluation of swallowing function. Fifty-two
      homogeneous semisolid foods not requiring mastication were given. Texture were
      measured twice using a rheometer (TPU-2S; Yamaden Co. Ltd., Tokyo, Japan).
      Texture characteristics were as follows: hardness, 1873 to 19,510 N/m(2) (mean
      9,129 N/m(2)); cohesiveness, 0.13 to 0.67 (mean 0.32); adhesiveness, 2 to 878
      J/m(3) (mean 209 J/m(3)); and gumminess, 546 to 8781 N/m(2) (mean 2908 N/m(2)).
      Patients sat during fiberoptic endoscopic evaluation and ingested a single
      semisolid food. The patients were asked to swallow 4 g of food, and the texture,
      pharyngeal residue, penetration into the larynx, and aspiration were evaluated.
      We observed and noted the association between the texture of foods and swallowing
      movements by videoendoscopy. RESULTS: Evaluating food texture by endoscopy
      revealed significant differences in adhesiveness according to residue deposition
      and significant differences in gumminess according to aspiration. CONCLUSIONS: We
      identified the textures of different semisolid foods as being either appropriate
      or inappropriate for poststroke dysphagic patients.

PMID- 21968094
TI  - Real-time RT-PCR for detection of Raspberry bushy dwarf virus, Raspberry leaf
      mottle virus and characterizing synergistic interactions in mixed infections.
AB  - Two TaqMan-based real-time One-Step RT-PCR assays were developed for the rapid
      and efficient detection of Raspberry bushy dwarf virus (RBDV) and Raspberry leaf
      mottle virus (RLMV), two of the most common raspberry viruses in North America
      and Europe. The primers and probes were designed from conserved fragments of the
      polymerase region of each virus and were effective for the detection of different
      isolates tested in this study. The RBDV assay amplified a 94bp amplicon and was
      able to detect as few as 30 viral copies. Whereas the RLMV assay amplified a
      180bp amplicon and detected as few as 300 viral copies from plant and aphid RNA
      extracts. Both assays were significantly more sensitive than their corresponding
      conventional RT-PCR methods. The sensitivity of the RLMV assay was also tested on
      single aphids after a fixed acquisition access period (AAP). In addition, the
      assays revealed a novel synergistic interaction between the two viruses, where
      the concentration of RBDV was enhanced ~400-fold when it occurred in combination
      with RLMV compared to its concentration in single infections. The significance of
      this finding and the importance of the development of real-time RT-PCR assays for
      the detection of RBDV and RLMV are discussed.

PMID- 21968095
TI  - A novel RealTime HIV-1 Qualitative assay for the detection of HIV-1 nucleic acids
      in dried blood spots and plasma.
AB  - Abbott RealTime HIV-1 Qualitative is an in vitro real-time PCR assay for
      detecting HIV-1 nucleic acids in human plasma and dried blood spots (DBS). The
      assay was designed to be used in diagnosis of HIV-1 infections in pediatric and
      adult patients, with an emphasis on the applicability in resource-limited
      settings. Use of DBS facilitates specimen collection from remote areas and
      transportation to testing laboratories. Small sample input requirement
      facilitates testing of specimens with limited collection volume. The Abbott
      RealTime HIV-1 Qualitative assay is capable of detecting HIV-1 group M subtypes A
      H, group O and group N samples. HIV-1 virus concentrations detected with 95%
      probability were 80 copies/mL of plasma using the plasma protocol, and 2469
      copies/mL of whole blood using the DBS protocol. The assay detected HIV-1
      infection in 13 seroconversion panels an average 10.5 days earlier than an HIV-1
      antibody test and 4.9 days earlier than a p24 antigen test. For specimens
      collected from 6 weeks to 18 months old infants born to HIV-1 positive mothers,
      assay results using both the DBS and plasma protocols agreed well with the Roche
      Amplicor HIV-1 DNA Test version 1.5 (95.5% agreement for DBS and 97.8% agreement
      for plasma).

PMID- 21968096
TI  - The Oxford classification of IgA nephropathy: a retrospective analysis.
AB  - BACKGROUND/AIMS: The Oxford classification of IgA nephropathy (IgAN) assesses the
      presence of mesangial hypercellularity >=50% (M1 vs. 0), endocapillary
      proliferation (E1 vs. 0), segmental glomerulosclerosis (S1 vs. 0), tubular
      atrophy/interstitial fibrosis >25 or 50% (T1 or 2 vs. 0), and has been reported
      as having prognostic value. We studied the clinical significance of the
      classification in our adult patients with IgAN. METHODS: Retrospective study of
      54 patients with biopsy-proven IgAN seen from 1983 to 2009. The correlation
      between the Oxford classification and baseline renal function was assessed. The
      primary endpoint was a 50% reduction in eGFR or end-stage renal disease.
      Predictors for progression to the endpoint were determined by multivariate
      analyses. RESULTS: Patients were 41 +/- 15 years of age with a serum creatinine
      of 1.5 +/- 0.8 mg/dl, eGFR of 61 +/- 24 ml/min/1.73 m(2), and proteinuria of 2.0
      +/- 1.6 g/day. Oxford classifications were as follows: M1 = 72%, E1 = 20%, S1 =
      81%, and T1 = 13%/T2 = 22%. During the follow-up of 5.8 +/- 4.8 years, 19% of
      patients reached the primary endpoint. While the Oxford classification was
      associated with progressive renal disease, only the T score (T0, T1, T2) was
      predictive of outcome with 6, 29, and 50% of patients (p = 0.002) reaching the
      primary endpoint. The 10-year renal survival for T0, T1, and T2 was 100, 50, and
      17%, respectively (p < 0.001). By multivariate analysis, the hazard ratio for
      reaching the primary endpoint was 32 for patients with T >=1 versus T0 (p =
      0.01). CONCLUSIONS: In our experience, the Oxford classification predicts
      progressive renal disease, but the degree of tubulointerstitial fibrosis was the
      only feature independently predictive of outcome.

PMID- 21968097
TI  - Persisting right-sided chylothorax in a patient with chronic lymphocytic
      leukemia: a case report.
AB  - INTRODUCTION: Chylothorax caused by chronic lymphocytic leukemia is very rare and
      the best therapeutic approach, especially the role of modern immunochemotherapy,
      is not yet defined. CASE PRESENTATION: We present the case of a 65-year-old male
      Caucasian patient with right-sided chylothorax caused by a concomitantly
      diagnosed chronic lymphocytic leukemia. As first-line treatment four cycles of an
      immunochemotherapy, consisting of fludarabine, cyclophosphamide and rituximab
      were administered. In addition, our patient received total parenteral nutrition
      for the first two weeks of treatment. Despite the very good clinical response of
      the lymphoma to treatment, the chylothorax persisted and percutaneous
      radiotherapy of the thoracic duct was applied. However, eight weeks after the
      radiotherapy the chylothorax still persisted and our patient agreed to a surgical
      intervention. A ligation of the thoracic duct via a muscle sparing thoracotomy
      was performed, resulting in a complete cessation of the pleural effusion. Apart
      from the first two weeks our patient was treated on an out-patient basis for
      nearly six months. CONCLUSION: In this case of chylothorax caused by chronic
      lymphocytic leukemia, immunochemotherapy in combination with conservative
      treatment, and even consecutive radiotherapy, were not able to stop pleural
      effusion, despite the very good clinical response of the chronic lymphocytic
      leukemia to treatment.Out-patient management using repetitive thoracocenteses can
      be safe as bridging until definitive surgical ligation of the thoracic duct.

PMID- 21968098
TI  - Interactions between beta-lactoglobulin and casein glycomacropeptide on foaming.
AB  - The aim of this work was to study the effect of interactions between casein
      glycomacropeptide (CMP) and beta-lactoglobulin (beta-lg) at pH 6.5 and 3.5 on the
      foaming properties of the mixed systems with different CMP:beta-lg ratios. The
      foaming properties were determined by the bubbling method with a Foamscan
      instrument. A highest overall foam capacity (OFC), foaming capacity (FC) and
      mainly stability of mixed foams at pH 3.5, as compared to the mixed foams at pH
      6.5 or the foams of CMP and beta-lg was observed. At pH 6.5, the stability of
      mixed foams decreased with increasing the CMP content, while OFC and FC values
      were similar to beta-lg foam. The performance of the mixed systems was discussed
      in relation with the interactions between CMP and beta-lg in the aqueous phase
      (as observed by dynamic light scattering and differential scanning calorimetry in
      previous works).

PMID- 21968099
TI  - PUF-8 suppresses the somatic transcription factor PAL-1 expression in C. elegans
      germline stem cells.
AB  - RNA-binding proteins of the PUF family are well conserved post-transcriptional
      regulators that control a variety of developmental processes. The C. elegans
      protein PUF-8 is essential for several aspects of germ cell development including
      the maintenance of germline stem cells (GSCs). To explore the molecular
      mechanisms underlying its function, we have identified 160 germline-expressed
      mRNAs as potential targets of PUF-8. We generated GFP::H2B-3' UTR fusions for 17
      mRNAs to assay their post-transcriptional regulation in germ cells. Twelve
      transgenes were not expressed in the mitotic germ cells, and depletion of PUF-8
      led to misexpression of six of them in these cells. In contrast, the expression
      of 3' UTR fusion of hip-1, which encodes the HSP-70 interacting protein, was
      dependent on PUF-8. These results indicate that PUF-8 may regulate the expression
      of its targets both negatively as well as positively. We investigated the PUF-8
      mediated post-transcriptional control of one mRNA, namely pal-1, which encodes a
      homeodomain transcription factor responsible for muscle development. Our results
      show that PUF-8 binds in vitro to specific sequences within pal-1 3' UTR that are
      critical for post-transcriptional suppression in GSCs. Removal of PUF-8 resulted
      in PAL-1 misexpression, and PAL-1-dependent misexpression of the myogenic
      promoter HLH-1 in germ cells. We propose that PUF-8 protects GSCs from the
      influence of somatic differentiation factors such as PAL-1, which are produced in
      the maternal germline but meant for embryogenesis.

PMID- 21968100
TI  - Visualizing digestive organ morphology and function using differential fatty acid
      metabolism in live zebrafish.
AB  - Lipids are essential for cellular function as sources of fuel, critical signaling
      molecules and membrane components. Deficiencies in lipid processing and transport
      underlie many metabolic diseases. To better understand metabolic function as it
      relates to disease etiology, a whole animal approach is advantageous, one in
      which multiple organs and cell types can be assessed simultaneously in vivo.
      Towards this end, we have developed an assay to visualize fatty acid (FA)
      metabolism in larval zebrafish (Danio rerio). The method utilizes egg yolk
      liposomes to deliver different chain length FA analogs (BODIPY-FL) to six day-old
      larvae. Following liposome incubation, larvae accumulate the analogs throughout
      their digestive organs, providing a comprehensive readout of organ structure and
      physiology. Using this assay we have observed that different chain length FAs are
      differentially transported and metabolized by the larval digestive system. We
      show that this assay can also reveal structural and metabolic defects in
      digestive mutants. Because this labeling technique can be used to investigate
      digestive organ morphology and function, we foresee its application in diverse
      studies of organ development and physiology.

PMID- 21968102
TI  - Synthesis of NaYF4:Yb3+, Er3+ upconversion nanoparticles in normal
      microemulsions.
AB  - An interface-controlled reaction in normal microemulsions (water/ethanol/sodium
      oleate/oleic acid/n-hexane) was designed to prepare NaYF4:Yb3+, Er3+ upconversion
      nanoparticles. The phase diagram of the system was first studied to obtain the
      appropriate oil-in-water microemulsions. Transmission electron microscopy and X
      ray powder diffractometer measurements revealed that the as-prepared
      nanoparticles were spherical, monodisperse with a uniform size of 20 nm, and of
      cubic phase with good crystallinity. Furthermore, these nanoparticles have good
      dispersibility in nonpolar organic solvents and exhibit visible upconversion
      luminescence of orange color under continuous excitation at 980 nm. Then, a
      thermal treatment for the products was found to enhance the luminescence
      intensity. In addition, because of its inherent merit in high yielding and being
      economical, this synthetic method could be utilized for preparation of the UCNPs
      on a large scale.

PMID- 21968101
TI  - Six1 and Eya1 are critical regulators of peri-cloacal mesenchymal progenitors
      during genitourinary tract development.
AB  - The evolutionarily conserved Six1-Eya1 transcription complex is central to
      mammalian organogenesis, and deletion of these genes in mice results in
      developmental anomalies of multiple organs that recapitulate human branchio-oto
      renal (BOR) and DiGeorge syndromes. Here, we report that both Six1 and Eya1 are
      strongly expressed in the peri-cloacal mesenchyme (PCM) surrounding the cloaca,
      the terminal end of hindgut dilation. Six1 and Eya1 are absent from the intra
      cloacal mesenchyme (ICM), a cell mass that divides the cloaca into dorsal hindgut
      and ventral urogenital sinus. Deletion of either or both Six1 and Eya1 genes
      results in a spectrum of genitourinary tract defects including persistent cloaca 
      hypoplastic perineum tissue between external urogenital and anorectal tracts;
      hypospadias - ectopic ventral positioning of the urethral orifice; and
      hypoplastic genitalia. Analyses of critical signaling molecules indicate normal
      expression of Shh in the cloaca and cloaca-derived endodermal epithelia. Using a
      Cre/loxP genetic fate mapping strategy, we demonstrate that Six1-positive PCM
      progenitors give rise to the most caudal structures of the body plan including
      the urogenital and anorectal complex, and the perineum region. Thus, Six1 and
      Eya1 are key regulators of both upper and lower urinary tract morphogenesis.
      Results from this study uncover essential roles of the PCM progenitors during
      genitourinary tract formation.

PMID- 21968103
TI  - Development and evaluation of a selective medium for Brucella suis.
AB  - A new selective medium, named LNIV-M, has been developed for isolation of
      Brucella suis. In this work, we evaluated the growth of B. suis reference and
      field strains from domestic pigs in different basal media and the susceptibility
      to different antibiotics contained in the currently used Farrell's and modified
      Thayer-Martin media. We also determined the efficacy of LNIV-M and its diagnostic
      performance for isolating B. suis from wild boar tissue samples. A total of 1649
      samples from 918 hunter-harvested wild boars were cultured in LNIV-M, Farrell's
      and modified Thayer-Martin media. One hundred and thirty-nine (8.4%) samples from
      63 (6.9%) animals resulted in a positive culture. LNIV-M detected 93.6% and 62.6%
      of positive animals and samples, respectively, while Farrell's and modified
      Thayer-Martin media detected, respectively, 92.1% and 79.4% of positive animals
      and 58.3% and 59.7% of samples. These results confirm the adequate diagnostic
      performance of LNIV-M in the isolation of B. suis.

PMID- 21968104
TI  - The association of genetic variants in interleukin-1 genes with cognition:
      findings from the cardiovascular health study.
AB  - The inflammatory cytokine interleukin-1 (IL1) potentially plays a role in
      cognitive deterioration through pathology due to a dementing disorder or due to
      an aging process. Study of genetic variants in the IL1 genes has been mostly
      limited to diseases such as Alzheimer's, however, there may be benefit to
      studying a continuous measure of cognition. Using data from the Cardiovascular
      Health Study, we evaluate genetic variation in the genes encoding inflammatory
      agonists IL1A and IL1B, and the antagonist IL1RN, with repeated measures of
      global cognition (3MS) and processing speed (DSST), using mixed effects models.
      We found statistically significant minor allele SNP associations with baseline
      performance on the 3MS in the IL1RN gene for Caucasians (rs17042917: beta=0.47,
      95%CI=0.09, 0.85, p=0.016; rs4251961: beta=-0.36, 95%CI=-0.13,-0.60, p=0.0027;
      rs931471: beta=0.39, 95%CI=0.13, 0.65, p=0.0032), and the IL1B gene for African
      Americans (rs1143627: beta=1.6, 95%CI=0.48, 2.8; p=0.006 and rs1143634:
      beta=2.09, 95%CI=0.39, 3.8; p=0.016). Associations appear to be weaker in a
      subgroup with higher education level. Upon removing those diagnosed with
      dementia, effect sizes and statistical significance attenuated. These results
      provide supporting evidence that genetic variants in IL1 genes may be involved in
      inflammatory-related lowered cognition, that higher education may modify genetic
      predisposition, and that these associations may be driven by a dementia process.

PMID- 21968105
TI  - Viruses and human brain tumors:  cytomegalovirus enters the fray.
AB  - Medulloblastoma is the most common malignant brain tumor in children. Overall
      survival rates have improved in recent years as a result of risk-stratified
      treatment regimens. However, medulloblastoma remains associated with substantial
      mortality, and survivors often experience debilitating neurological,
      endocrinological, and social sequelae as a result of treatment. Targeted and less
      toxic therapeutic strategies are therefore needed. In this issue of the JCI,
      Baryawno et al. report their findings that a large percentage of primary
      medulloblastomas and medulloblastoma cell lines are infected with human
      cytomegalovirus (HCMV) and suggest that targeting this virus could provide a new
      way to treat individuals with medulloblastoma.

PMID- 21968106
TI  - There's a goat behind door number 3: from Monty Hall to medicine.
AB  - In the 18th century, Thomas Bayes developed his eponymous theorem that teaches us
      that pretest probabilities can be altered by new information, such as when game
      show host Monty Hall revealed the goat behind one of the remaining doors in
      "Let's Make A Deal." Bayesian analysis is a key feature of many medical
      decisions. In this issue of the JCI, Lee and colleagues apply this concept to
      inflammatory bowel disease to identify gene expression-based biomarkers of
      disease severity. Importantly, these biomarkers allowed patients to be stratified
      into two groups: those at high risk for disease recurrence or the need for
      immunosuppressive treatment escalation and those with a more benign disease
      course.

PMID- 21968107
TI  - Informed reasoning: repositioning of nitisinone  to treat oculocutaneous
      albinism.
AB  - Oculocutaneous albinism (OCA) is a group of genetic disorders characterized by
      hypopigmentation of the skin, hair, and eyes. Affected individuals experience
      reduced visual acuity and substantially increased skin cancer risk. There are
      four major types of OCA (OCA1-OCA4) that result from disruption in production of
      melanin from tyrosine. Current treatment options for individuals with OCA are
      limited to attempts to correct visual problems and counseling to promote use of
      sun protective measures. However, Onojafe et al., reporting in this issue of the
      JCI, provide hope for a new treatment approach for OCA, as they demonstrate that
      treating mice that model OCA-1b with nitisinone, which is FDA approved for
      treating hereditary tyrosinemia type 1, elevates plasma tyrosine levels, and
      increases eye and hair pigmentation.

PMID- 21968108
TI  - Lessons in human biology from a monogenic  pancreatic beta cell disease.
AB  - Deciphering the complexities of human beta cell physiology is critical to our
      understanding of the pathophysiology behind both type 1 and type 2 diabetes. One
      way to do this is to study individuals with congenital hyperinsulinism (CHI), a
      rare genetic disease characterized by dysregulation of insulin secretion
      resulting in hypoglycemia. In this issue of the JCI, Henquin et al. report in
      vitro studies of pancreatic tissue obtained from CHI patients during therapeutic
      pancreatectomy that have yielded exciting new insights into human beta cell
      physiology. The data validate and extend observations made in model organisms.

PMID- 21968109
TI  - ApoE controls the interface linking lipids  and inflammation in atherosclerosis.
AB  - Atherosclerosis is a chronic inflammatory disease of the arterial walls that
      often leads to myocardial infarction and/or stroke. Hypercholesterolemia and an
      imbalance of peripheral leukocyte counts, leading to arterial leukocyte
      infiltration, are considered independent risk factors for atherosclerosis.
      However, in this issue of the JCI, Murphy and colleagues identify a mechanistic
      link between hypercholesterolemia, leukocytosis, and the subsequent development
      of atherosclerotic lesions in mice. These findings could pave the way for the
      development of novel treatment strategies to control leukocyte homeostasis and
      atherosclerosis.

PMID- 21968110
TI  - Nitisinone improves eye and skin  pigmentation defects in a mouse model  of
      oculocutaneous albinism.
AB  - Mutation of the tyrosinase gene (TYR) causes oculocutaneous albinism, type 1
      (OCA1), a condition characterized by reduced skin and eye melanin pigmentation
      and by vision loss. The retinal pigment epithelium influences postnatal visual
      development. Therefore, increasing ocular pigmentation in patients with OCA1
      might enhance visual function. There are 2 forms of OCA1, OCA-1A and OCA-1B.
      Individuals with the former lack functional tyrosinase and therefore lack
      melanin, while individuals with the latter produce some melanin. We hypothesized
      that increasing plasma tyrosine concentrations using nitisinone, an FDA-approved
      inhibitor of tyrosine degradation, could stabilize tyrosinase and improve
      pigmentation in individuals with OCA1. Here, we tested this hypothesis in mice
      homozygous for either the Tyrc-2J null allele or the Tyrc-h allele, which model
      OCA-1A and OCA-1B, respectively. Only nitisinone-treated Tyrc-h/c-h mice
      manifested increased pigmentation in their fur and irides and had more pigmented
      melanosomes. High levels of tyrosine improved the stability and enzymatic
      function of the Tyrc-h protein and also increased overall melanin levels in
      melanocytes from a human with OCA-1B. These results suggest that the use of
      nitisinone in OCA-1B patients could improve their pigmentation and potentially
      ameliorate vision loss.

PMID- 21968111
TI  - In vitro insulin secretion by pancreatic tissue from infants with diazoxide
      resistant congenital hyperinsulinism deviates from model predictions.
AB  - Congenital hyperinsulinism (CHI) is the major cause of persistent neonatal
      hypoglycemia. CHI most often occurs due to mutations in the ABCC8 (which encodes
      sulfonylurea receptor 1) or KCNJ11 (which encodes the potassium channel Kir6.2)
      gene, which result in a lack of functional KATP channels in pancreatic beta
      cells. Diffuse forms of CHI (DiCHI), in which all beta cells are abnormal, often
      require subtotal pancreatectomy, whereas focal forms (FoCHI), which are
      characterized by localized hyperplasia of abnormal beta cells, can be cured by
      resection of the lesion. Here, we characterized the in vitro kinetics of insulin
      secretion by pancreatic fragments from 6 DiCHI patients and by focal lesion and
      normal adjacent pancreas from 18 FoCHI patients. Responses of normal pancreas
      were similar to those reported for islets from adult organ donors. Compared with
      normal pancreas, basal insulin secretion was elevated in both FoCHI and DiCHI
      tissue. Affected tissues were heterogeneous in their secretory responses, with
      increased glucose levels often producing a rapid increase in insulin secretion
      that could be followed by a paradoxical decrease below prestimulatory levels. The
      KATP channel blocker tolbutamide was consistently ineffective in stimulating
      insulin secretion; conversely, the KATP channel activator diazoxide often caused
      an unanticipated increase in insulin secretion. These observed alterations in
      secretory behavior were similar in focal lesion and DiCHI tissue, and independent
      of the specific mutation in ABCC8 or KCNJ11. They cannot be explained by classic
      models of beta cell function. Our results provide insight into the excessive and
      sometimes paradoxical changes in insulin secretion observed in CHI patients with
      inactivating mutations of KATP channels.

PMID- 21968113
TI  - Initial adhesion of Listeria monocytogenes to solid surfaces under liquid flow.
AB  - Some strains of the food borne pathogen Listeria monocytogenes persist in food
      processing environments. The exact reason behind this phenomenon is not known,
      but strain differences in the ability to adhere to solid surfaces could offer an
      explanation. In the present work, initial adhesion of nine strains of L.
      monocytogenes was investigated under liquid flow at two levels of shear stress on
      six different surfaces using a flow chamber set-up with microscopy measurements.
      The surfaces tested were glass and PVC, and glass coated with beef extract,
      casein, and homogenised and unhomogenised milk. In addition, the effect of prior
      environmental stress (5% NaCl, low nutrient availability) on initial adhesion was
      investigated. The hydrophobicity of the investigated surfaces was determined by
      contact angle measurements and the surface properties of the investigated L.
      monocytogenes strains were determined using Microbial Adhesion To Solvents
      (MATS). All surfaces with the exception of PVC were found to be hydrophilic.
      Strain differences were found to significantly influence the initial adhesion
      rate (IAR) of all nine strains to all the surfaces (p<0.05) at both low and high
      shear stress. Furthermore, there was a significant effect of the surfaces tested
      (p<0.05) in the adhesion ability of almost all strains. The IAR was affected by
      flow rate (shear stress) as seen by a decrease in adhesion at high shear stress
      for most strains. A significant effect of interactions between strain-surface and
      strain-shear stress (p<0.001) was observed but not of interactions between
      surface-shear stress. No correlation between surface hydrophobicity and IAR was
      observed. Addition of 5% NaCl during propagation resulted in a decrease in IAR
      whilst propagation in low nutrient media caused an increase indicating a general
      change in surface characteristics under these conditions. Known persisting
      strains did not display general better adherence.

PMID- 21968114
TI  - Age related changes to perceptual surround suppression of moving stimuli.
AB  - Perceptual analogues of centre-surround suppression have been applied as indirect
      measures of cortical inhibitory function in several clinical disorders. Two tasks
      have been used: a centre-surround contrast perception task and a motion direction
      discrimination task, where the stimulus size and contrast is varied to measure
      surround suppression effects. The tasks are markedly different, yet previous
      literature implies that both measures indirectly assess inhibitory function and
      that results will be complementary. This is not the case for age-related effects
      on surround suppression, however, as previous reports using the different
      measures are conflicting. Here we use a low-spatial frequency, drifting grating
      version of the centre-surround contrast perception task, and compare results to
      those obtained with the motion direction task in a single group of older
      observers. Older adults demonstrate significantly increased perceptual surround
      suppression of contrast for drifting, high contrast stimuli. Using the motion
      discrimination task, older observers showed similar amounts of surround
      suppression for the largest stimulus. This study confirms that visual surround
      suppression is altered by ageing. The complexity of neuronal systems involved in
      centre-surround interactions makes it unlikely that a single perceptual task will
      be sufficient to describe the effects of clinical disorders on surround
      suppression.

PMID- 21968112
TI  - ApoE regulates hematopoietic  stem cell proliferation, monocytosis,  and monocyte
      accumulation  in atherosclerotic lesions in mice.
AB  - Leukocytosis is associated with increased cardiovascular disease risk in humans
      and develops in hypercholesterolemic atherosclerotic animal models. Leukocytosis
      is associated with the proliferation of hematopoietic stem and multipotential
      progenitor cells (HSPCs) in mice with deficiencies of the cholesterol efflux
      promoting ABC transporters ABCA1 and ABCG1 in BM cells. Here, we have determined
      the role of endogenous apolipoprotein-mediated cholesterol efflux pathways in
      these processes. In Apoe-/- mice fed a chow or Western- type diet, monocytosis
      and neutrophilia developed in association with the proliferation and expansion of
      HSPCs in the BM. In contrast, Apoa1-/- mice showed no monocytosis compared with
      controls. ApoE was found on the surface of HSPCs, in a proteoglycan-bound pool,
      where it acted in an ABCA1- and ABCG1-dependent fashion to decrease cell
      proliferation. Accordingly, competitive BM transplantation experiments showed
      that ApoE acted cell autonomously to control HSPC proliferation, monocytosis,
      neutrophilia, and monocyte accumulation in atherosclerotic lesions. Infusion of
      reconstituted HDL and LXR activator treatment each reduced HSPC proliferation and
      monocytosis in Apoe-/- mice. These studies suggest a specific role for
      proteoglycanbound ApoE at the surface of HSPCs to promote cholesterol efflux via
      ABCA1/ABCG1 and decrease cell proliferation, monocytosis, and atherosclerosis.
      Although endogenous apoA-I was ineffective, pharmacologic approaches to
      increasing cholesterol efflux suppressed stem cell proliferative responses.

PMID- 21968115
TI  - The roles of various plasma species in the plasma and plasma-catalytic removal of
      low-concentration formaldehyde in air.
AB  - The contributions of various plasma species to the removal of low-concentration
      formaldehyde (HCHO) in air by DC corona discharge plasma in the presence and
      absence of downstream MnO(x)/Al(2)O(3) catalyst were systematically investigated
      in this study. Experimental results show that HCHO can be removed not only by
      short-living active species in the discharge zone, but also by long-living
      species except O(3) downstream the plasma reactor. O(3) on its own is incapable
      of removing HCHO in the gas phase but when combined with the MnO(x)/Al(2)O(3)
      catalyst, considerable HCHO conversion is seen, well explaining the greatly
      enhanced HCHO removal by combining plasma with catalysis. The plasma-catalysis
      hybrid process where HCHO is introduced through the discharge zone and then the
      catalyst bed exhibits the highest energy efficiency concerning HCHO conversion,
      due to the best use of plasma-generated active species in a two-stage HCHO
      destruction process. Moreover, the presence of downstream MnO(x)/Al(2)O(3)
      catalyst significantly reduced the emission of discharge byproducts (O(3)) and
      organic intermediates (HCOOH).

PMID- 21968116
TI  - Water quality assessment in the rivers along the water conveyance system of the
      Middle Route of the South to North Water Transfer Project (China) using
      multivariate statistical techniques and receptor modeling.
AB  - A total of 190 grab water samples were collected from 19 rivers along the water
      conveyance system of the Middle Route of China's interbasin South to North Water
      Transfer Project (MRSNWTP). Multivariate statistics including principal
      component/factor analysis (PCA/FA), analysis of variance (ANOVA), and cluster
      analysis (CA) were employed to assess water quality, and the receptor model of
      factor analysis-multiple linear regression (FA-MLR) was used for source
      identification/apportionment of pollutants from natural processes and
      anthropogenic activities to river waters. Our results revealed that river waters
      were primarily polluted by COD(Mn), BOD, NH(4)(+)-N, TN, TP, and Cd with
      remarkably spatio-temporal variability, and there were increasing industrial
      effluents in rivers northward. FA/PCA identified four classes of water quality
      parameters, i.e., mineral composition, toxic metals, nutrients, and organic
      pollutants. CA classified the selective 19 rivers into three groups reflecting
      their varying water pollution levels of moderated pollution, high pollution, and
      very high pollution. The FA-MLR receptor modeling revealed predominantly
      anthropogenic inputs to river solutes in Beijing and Tianjin, i.e., 77% of
      nitrogen and 90% of phosphorus from industry, and 80% of COD(Mn) from domestics.
      This study is critical for water allocation and division in the water-receiving
      areas using the existing rivers for MRSNWTP.

PMID- 21968117
TI  - Waste washing pre-treatment of municipal and special waste.
AB  - Long-term pollution potential in landfills is mainly related to the quality of
      leachate. Waste can be conveniently treated prior to landfilling with an aim to
      minimizing future emissions. Washing of waste represents a feasible pre-treatment
      method focused on controlling the leachable fraction of residues and relevant
      impact. In this study, non-recyclable plastics originating from source
      segregation, mechanical-biological treated municipal solid waste (MSW), bottom
      ash from MSW incineration and automotive shredder residues (ASR) were treated and
      the removal efficiency of washing pre-treatment prior to landfilling was
      evaluated. Column tests were performed to simulate the behaviour of waste in
      landfill under aerobic and anaerobic conditions. The findings obtained revealed
      how waste washing treatment (WWT) allowed the leachability of contaminants from
      waste to be reduced. Removal rates exceeding 65% were obtained for dissolved
      organic carbon (DOC), chemical oxygen demand (COD) and Total Kjeldahl Nitrogen
      (TKN). A percentage decrease of approximately 60% was reached for the leachable
      fraction of chlorides, sulphates, fluoride and metals, as proved by a reduction
      in electric conductivity values (70%).

PMID- 21968119
TI  - Treatment of nanowaste via fast crystal growth: with recycling of nano-SnO2 from
      electroplating sludge as a study case.
AB  - The treatment of industrial sludge containing amorphous/nanophase metal oxides or
      hydroxides is one of the vital issues in hazardous waste disposal. In this work,
      we developed a strategy to recycle nano-SnO(2) from tinplate electroplating
      sludge. It revealed that the major components of this sludge were acid soluble Sn
      and Fe amorphous phases. By introducing NaOH as a mineralizer, a fast growth of
      amorphous Sn compound into acid-insoluble SnO(2) nanowires was achieved
      selectively. Thus, the as-formed nano-SnO(2) could be recycled via dissolving
      other solid compositions in the sludge by using acid. The role of NaOH on
      accelerating both the Oriented Attachment (OA) and Ostwald Ripening (OR) growth
      of SnO(2) was discussed, which was regarded as a critical factor for treating the
      sludge. A pilot-scale experiment was conducted to treat 2.3 kg original sludge
      and the recycling of about 90 g nano-SnO(2) was achieved. We anticipate this work
      can provide a good example for the recycling of valuable metals from industrial
      sludge containing fine metal oxides or hydroxides.

PMID- 21968120
TI  - Properties improvement of paper mill sludge-based granular activated carbon
      fillers for fluidized-bed bioreactor by bentonite (Na) added and acid washing.
AB  - Properties improvement of paper mill sludge (PMS) based granular activated carbon
      fillers for fluidized-bed bioreactor (FBBR) was investigated in this study.
      Bentonite (Na) powders were blended in the dewatered paper mill sludge powders to
      strengthen the abrasion resistance strength of the fillers. Different acid
      washing treatments were studied to produce FBBR fillers with optimum performance.
      The results indicated that granulation was easy and the abrasion resistance
      strength of the fillers increased by 15% with 8 wt% of bentonite (Na) added. Acid
      washing treatment prior to activation had a better effect on the removal of Fe
      than post-activation acid washing treatment. HCl was the most appropriate acid
      during the acid washing treatment. The optimum acid washing treatment was carried
      out prior to activation with 2M HCl soaking for 6h. After acid washing treatment,
      the fillers with grain density of 1170 kg/m(3), specific surface area of 176
      m(2)/g were obtained.

PMID- 21968121
TI  - Effects of chloride ion on degradation of Acid Orange 7 by sulfate radical-based
      advanced oxidation process: implications for formation of chlorinated aromatic
      compounds.
AB  - Sodium chloride is a common salt used during textile wet processes. Here a dual
      effect of chloride (i.e. inhibitory and accelerating effect) on azo dye (Acid
      Orange 7, AO7) degradation in an emerging cobalt/peroxymonosulfate (Co/PMS)
      advanced oxidation process (AOP) was reported. Compared to OH-based AOPs, high
      concentrations of chloride (>5mM) can significantly enhance dye decoloration
      independent of the presence of the Co(2+) catalyst, but did greatly inhibit dye
      mineralization to an extent which was closely dependent upon the chloride
      content. Both UV-vis absorbance spectra and AOX determination indicated the
      formation of some refractory byproducts. Some chlorinated aromatic compounds,
      including 3-chloroisocoumain, 2-chloro-7-hydroxynaphthalene, 1,3,5-trichloro-2
      nitrobenzene and tetrachlorohydroquione, were identified by GC-MS measurement in
      both Co/PMS/Cl(-) and PMS/Cl(-) reaction systems. Based on those experimental
      results, two possible branched (SO(4)(-)radical-based and non-radical) reaction
      pathways are proposed. This is one of the very few studies dealing with
      chlorinated organic intermediates formed via chlorine radical/active chlorine
      species (HOCl/Cl(2)) attack on dye compounds. Therefore, this finding may have
      significant technical implications for utilizing Co/PMS regent to detoxify
      chloride-rich azo dyes wastewater.

PMID- 21968122
TI  - Persulfate activation by naturally occurring trace minerals.
AB  - The potential for 13 naturally occurring minerals to mediate the decomposition of
      persulfate and generate a range of reactive oxygen species was investigated to
      provide fundamental information on activation mechanisms when persulfate is used
      for in situ chemical oxidation (ISCO). Only four of the minerals (cobaltite,
      ilmenite, pyrite, and siderite) promoted the decomposition of persulfate more
      rapidly than persulfate-deionized water control systems. The other nine minerals
      decomposed persulfate at the same rate or more slowly than the control systems.
      Mineral-mediated persulfate activation was conducted with the addition of one of
      three probe compounds to detect the generation of reactive oxygen species:
      anisole (sulfate+hydroxyl radical), nitrobenzene (hydroxyl radical), and
      hexachloroethane (reductants and nucleophiles). The reduced mineral pyrite
      promoted rapid generation of sulfate+hydroxyl radical. However, the remainder of
      the minerals provided minimal potential for the generation of reactive oxygen
      species. The results of this research demonstrate that the majority of naturally
      occurring trace minerals do not activate persulfate to generate reactive oxygen
      species, and other mechanisms of activation are necessary to promote contaminant
      destruction in the subsurface during persulfate ISCO.

PMID- 21968123
TI  - Degradation of crystal violet by an FeGAC/H2O2 process.
AB  - Because of the growing concern over highly contaminated crystal violet (CV)
      wastewater, an FeGAC/H(2)O(2) process was employed in this research to treat CV
      contaminated wastewater. The experimental results indicated that the presence of
      iron oxide-coated granular activated carbon (FeGAC) greatly improved the
      oxidative ability of H(2)O(2) for the removal of CV. For instance, the removal
      efficiencies of H(2)O(2), GAC, FeGAC, GAC/H(2)O(2) and FeGAC/H(2)O(2) processes
      were 10%, 44%, 40%, 43% and 71%, respectively, at test conditions of pH 3 and
      7.4mM H(2)O(2). FeGAC/H(2)O(2) combined both the advantages of FeGAC and
      H(2)O(2). FeGAC had a good CV adsorption ability and could effectively catalyze
      the hydrogen peroxide oxidation reaction. Factors (including pH, FeGAC dosage and
      H(2)O(2) dosage) affecting the removal of CV by FeGAC/H(2)O(2) were investigated
      in this research as well. In addition, the reaction intermediates were separated
      and identified using HPLC-ESI-MS. The N-demethylation step might be the main
      reaction pathway for the removal of CV. The reaction mechanisms for the process
      proposed in this research might be useful for future application of this
      technology to the removal of triphenylmethane (TPM) dyes.

PMID- 21968124
TI  - Self/non-self discrimination in angiosperm self-incompatibility.
AB  - Self-incompatibility (SI) in angiosperms prevents inbreeding and promotes
      outcrossing to generate genetic diversity. In many angiosperms, self/non-self
      recognition in SI is accomplished by male-specificity and female-specificity
      determinants (S-determinants), encoded at the S-locus. Recent studies using
      genetic, molecular biological and biochemical approaches have revealed that
      angiosperms utilize diverse self/non-self discrimination systems, which can be
      classified into two fundamentally different systems, self-recognition and non
      self recognition systems. The self-recognition system, adopted by Brassicaceae
      and Papaveraceae, depends on a specific interaction between male and female S
      determinants derived from the same S-haplotype. The non-self recognition system,
      found in Solanaceae, depends on non-self (different S-haplotype)-specific
      interaction between male and female S-determinants, and the male S-determinant
      genes are duplicated to recognize diverse non-self female S-determinants.

PMID- 21968125
TI  - Sir Karl Popper, swans, and the general practitioner.

PMID- 21968127
TI  - Choice--a love Labour's lost.

PMID- 21968128
TI  - Experts foresee huge growth in genetic medicine.

PMID- 21968126
TI  - Estimating treatment effects for individual patients based on the results of
      randomised clinical trials.
AB  - OBJECTIVES: To predict treatment effects for individual patients based on data
      from randomised trials, taking rosuvastatin treatment in the primary prevention
      of cardiovascular disease as an example, and to evaluate the net benefit of
      making treatment decisions for individual patients based on a predicted absolute
      treatment effect. SETTING: As an example, data were used from the Justification
      for the Use of Statins in Prevention (JUPITER) trial, a randomised controlled
      trial evaluating the effect of rosuvastatin 20 mg daily versus placebo on the
      occurrence of cardiovascular events (myocardial infarction, stroke, arterial
      revascularisation, admission to hospital for unstable angina, or death from
      cardiovascular causes). Population 17,802 healthy men and women who had low
      density lipoprotein cholesterol levels of less than 3.4 mmol/L and high
      sensitivity C reactive protein levels of 2.0 mg/L or more. METHODS: Data from the
      Justification for the Use of Statins in Prevention trial were used to predict
      rosuvastatin treatment effect for individual patients based on existing risk
      scores (Framingham and Reynolds) and on a newly developed prediction model. We
      compared the net benefit of prediction based rosuvastatin treatment (selective
      treatment of patients whose predicted treatment effect exceeds a decision
      threshold) with the net benefit of treating either everyone or no one. RESULTS:
      The median predicted 10 year absolute risk reduction for cardiovascular events
      was 4.4% (interquartile range 2.6-7.0%) based on the Framingham risk score, 4.2%
      (2.5-7.1%) based on the Reynolds score, and 3.9% (2.5-6.1%) based on the newly
      developed model (optimal fit model). Prediction based treatment was associated
      with more net benefit than treating everyone or no one, provided that the
      decision threshold was between 2% and 7%, and thus that the number willing to
      treat (NWT) to prevent one cardiovascular event over 10 years was between 15 and
      50. CONCLUSIONS: Data from randomised trials can be used to predict treatment
      effect in terms of absolute risk reduction for individual patients, based on a
      newly developed model or, if available, existing risk scores. The value of such
      prediction of treatment effect for medical decision making is conditional on the
      NWT to prevent one outcome event. Trial registration number Clinicaltrials.gov
      NCT00239681.

PMID- 21968129
TI  - Donors should be tougher on poor countries that don't engage in health
      programmes.

PMID- 21968130
TI  - Reduction of alloantibodies via proteasome inhibition in cardiac transplantation.
AB  - BACKGROUND: The presence of alloantibodies in patients awaiting heart
      transplantation is associated with increased waiting time to transplant,
      increased risk of rejection after transplant, an increased risk of cardiac
      allograft vasculopathy, and decreased survival. So far, treatments to reduce
      circulating antibodies to allow transplantation have been limited. We report the
      first clinical experience using a plasma-cell-depleting strategy with bortezomib
      to reduce anti-HLA antibodies in the heart transplant population. METHODS: Six
      patients awaiting cardiac transplantation demonstrated persistently elevated anti
      HLA antibodies, despite receiving a course of treatment with intravenous
      immunoglobulin (IVIg) and rituximab. These patients then underwent supplemental
      therapy with bortezomib in conjunction with plasmapheresis. One additional
      patient awaiting cardiac transplantation with elevated anti-HLA antibodies
      required bortezomib treatment for amyloidosis. Antibody strength was monitored
      after completion of treatment by solid-phase (single-antigen-bead) assay.
      RESULTS: The mean calculated panel-reactive antibody (cPRA) was reduced from 62%
      to 35% following a course of bortezomib (p = 0.01). Six of 7 patients
      demonstrated a significant decline in antibody levels. One patient remained
      refractory to desensitization therapy and died from sepsis while awaiting heart
      transplantation. Four patients successfully underwent cardiac transplantation
      without evidence of rejection or graft dysfunction. One patient developed early
      post-transplant graft dysfunction and died at 1 month from sepsis. Infection was
      the most common adverse effect associated with desensitization. CONCLUSIONS: In
      this pilot study, use of plasmapheresis and bortezomib appeared to decrease cPRA,
      even in patients refractory to desensitization with IVIg/rituximab, thus
      increasing the chances that an acceptable donor heart will be available for the
      sensitized patient awaiting heart transplantation. However, desensitization is
      associated with an increased risk of infection. Further studies are warranted to
      determine whether the benefits of desensitization using this strategy outweigh
      the risks.

PMID- 21968131
TI  - HIV protease inhibitors induce metabolic dysfunction in part via increased JNK1/2
      pro-inflammatory signaling in L6 cells.
AB  - Protease inhibitors (PIs), such as atazanavir sulfate and ritonavir, are used
      clinically to prevent the progression of HIV and are known to induce insulin
      resistance. To determine whether PI-mediated insulin resistance is induced by
      activation of pro-inflammatory cascades, L6 skeletal muscle cells were treated +/
      atazanavir sulfate, ritonavir, or atazanavir sulfate + ritonavir, and +/-insulin.
      Treatment with atazanavir sulfate, ritonavir, or atazanavir sulfate + ritonavir
      for 24 or 48 h significantly increased basal glucose uptake (P<0.05) and
      atazanavir sulfate + ritonavir treatment increased basal glucose uptake
      significantly more than ritonavir or atazanavir sulfate treatment alone (P<0.05).
      Atazanavir sulfate + ritonavir treatment for 48 h completely prevented insulin
      stimulation of glucose uptake (P>0.05). When compared to untreated cells, basal
      palmitate uptake and oxidation was found to be significantly higher in cells
      treated with PIs alone or in combination (P<0.05). Prior PI treatment alone or in
      combination prevented (P>0.05) the insulin-mediated increase in palmitate uptake
      and the insulin-mediated decrease in palmitate oxidation observed in the control
      group. Atazanavir sulfate treatment alone or in combination with ritonavir
      significantly increased JNK1/2 phosphorylation when compared to the control or
      ritonavir group (P<0.05) and this was accompanied by a rise (P<0.05) in
      AKT(Ser473) phosphorylation in the basal state. Total JNK1/2 and p38 MAPK protein
      content and p38 MAPK phosphorylation state were not altered in any of the
      treatment groups (P>0.05). Our data indicate that, in muscle cells, PIs induce
      metabolic dysfunction that is not limited to insulin-sensitive metabolism and
      that is potentially mediated by a rise in JNK1/2 pro-inflammatory signaling.

PMID- 21968132
TI  - Uromodulin in renal transplant recipients: elevated urinary levels and bimodal
      association with graft failure.
AB  - BACKGROUND: Urinary uromodulin (UMOD) predicts renal prognosis in native kidneys,
      but data are conflicting. We investigated its prognostic impact for graft failure
      (GF) in renal transplant recipients (RTR; n = 600). METHODS: UMOD concentration
      was measured cross-sectionally in RTR at 6.0 years [2.6-11.4] post-transplant, in
      matched patients with native chronic kidney disease (CKD) and healthy subjects.
      In 59 cases, RTR allograft biopsies were reviewed. RESULTS: During a follow-up of
      5.3 years [4.5-5.7], GF had occurred in 7% of RTR. Median UMOD excretion (mg/24
      h) was 20.4 in RTR, 11.6 in CKD and 5.7 in controls (p < 0.001). There was a
      curvilinear association between UMOD excretion and baseline renal function (p <
      0.003) and death-censored GF, with 5.5, 11.5 and 4.0% of the cases in subsequent
      UMOD excretion tertiles, respectively (p = 0.002). On multivariate Cox regression
      analysis, hazard ratios for GF for the 1st and 3rd tertiles were 0.37 (p = 0.01)
      and 0.21 (p = 0.001), respectively. Interstitial fibrosis and tubular atrophy
      were more severe in the middle tertile (p = 0.007). CONCLUSIONS: Urinary UMOD is
      elevated in RTR and associated with graft function, morphology and outcome in a
      bimodal fashion. Dissection of the disparate mechanisms of GF prediction by
      urinary UMOD might provide new clues for its alleged pathogenetic significance in
      progressive renal function loss.

PMID- 21968133
TI  - Phrenic nerve block with ultrasound-guidance for treatment of hiccups: a case
      report.
AB  - INTRODUCTION: Persistent hiccups can be more than a simple and short-lived
      nuisance and therefore sometimes call for serious consideration. Hiccupping
      episodes that last only a few minutes may be annoying, but persistent hiccups may
      initiate many major complications. CASE PRESENTATION: A 72-year-old Caucasian man
      with spinal stenosis presented for L4-5 laminectomy under spinal anesthesia. The
      surgery and anesthesia, as well as the perioperative period, passed without any
      incident, except for persistent postoperative hiccups not responding to
      conservative and pharmacological treatment. Hiccups resulted in a prolonged
      hospital stay as they lasted until the seventh postoperative day. On that day, a
      right-sided ultrasound-guided phrenic nerve block with 5 ml of bupivacaine 5
      mg/ml with epinephrine was performed successfully with a single-injection
      technique. Ten minutes after the procedure the hiccups vanished and a partial
      sensomotoric block of his right shoulder developed. No adverse effect occurred;
      our patient could be discharged on the same day and the hiccups did not return.
      CONCLUSION: Ultrasound provides us with non-invasive information regarding
      anatomy and allows anesthesiologists to visualize needle insertion, to identify
      the exact location of the injected solution and to avoid such structures as
      arteries or veins. As such, this method should be actively utilized. In cases
      where both pharmacological and non-pharmacological treatments prove to be
      ineffective when treating persistent hiccups, a single-shot ultrasound-guided
      technique should be considered before the patient becomes exhausted.

PMID- 21968134
TI  - Simultaneous determination of nitrendipine and hydrochlorothiazide in
      spontaneously hypertensive rat plasma using HPLC with on-line solid-phase
      extraction.
AB  - A HPLC method with on-line solid phase extraction (SPE) and DAD detection was
      developed for the simultaneous determination of nitrendipine and
      hydrochlorothiazide in spontaneously hypertensive rat (SHR) plasma. Plasma
      samples (100 MUL) were injected directly onto a CAPCELL MF C(8) SPE column. High
      abundance proteins and most matrixes in plasma were removed by on-line SPE
      technology, while nitrendipine and hydrochlorothiazide trapped on the SPE column
      were effectively separated on a C(18) analytical column. The column temperature
      was maintained at 20 degrees C. The optimal detection wavelength was 237 nm for
      NTDP and 271 nm for HCTZ. The total analytical run time was 34 min. The proposed
      method was linear over the range 5-500 ng mL(-1) for nitrendipine and 10-1000 ng
      mL(-1) for hydrochlorothiazide. The lower limit of detection (LLOD) was 0.5 and
      0.6 ng mL(-1) for nitrendipine and hydrochlorothiazide, respectively. The
      sensitivity and precision of the method were within acceptable limits during
      validation period. The method was successfully used to investigate the
      pharmacokinetic characteristics of nitrendipine and hydrochlorothiazide in
      spontaneously hypertensive rats.

PMID- 21968135
TI  - Toward improved statistical methods for analyzing Cotinine-Biomarker health
      association data.
AB  - BACKGROUND: Serum cotinine, a metabolite of nicotine, is frequently used in
      research as a biomarker of recent tobacco smoke exposure. Historically,
      secondhand smoke (SHS) research uses suboptimal statistical methods due to
      censored serum cotinine values, meaning a measurement below the limit of
      detection (LOD). METHODS: We compared commonly used methods for analyzing
      censored serum cotinine data using parametric and non-parametric techniques
      employing data from the 1999-2004 National Health and Nutrition Examination
      Surveys (NHANES). To illustrate the differences in associations obtained by
      various analytic methods, we compared parameter estimates for the association
      between cotinine and the inflammatory marker homocysteine using complete case
      analysis, single and multiple imputation, "reverse" Kaplan-Meier, and logistic
      regression models. RESULTS: Parameter estimates and statistical significance
      varied according to the statistical method used with censored serum cotinine
      values. Single imputation of censored values with either 0, LOD or LOD/?2 yielded
      similar estimates and significance; multiple imputation method yielded smaller
      estimates than the other methods and without statistical significance. Multiple
      regression modelling using the "reverse" Kaplan-Meier method yielded
      statistically significant estimates that were larger than those from parametric
      methods. CONCLUSIONS: Analyses of serum cotinine data with values below the LOD
      require special attention. "Reverse" Kaplan-Meier was the only method inherently
      able to deal with censored data with multiple LODs, and may be the most accurate
      since it avoids data manipulation needed for use with other commonly used
      statistical methods. Additional research is needed into the identification of
      optimal statistical methods for analysis of SHS biomarkers subject to a LOD.

PMID- 21968136
TI  - In-vivo evidence of a role for nitric oxide in regulating the activity of the
      norepinephrine transporter.
AB  - We examined the role of nitric oxide (NO) in the regulation of neuronal uptake of
      norepinephrine (uptake-1) in rats under anesthesia. The effect on systolic blood
      pressure of two pressor drugs that work by different mechanisms, norepinephrine
      and angiotensin II, was explored in anesthetized rats under control conditions
      and after prevention of NO synthesis with Nw-nitro-L-arginine (L-NNA). The
      results showed that whereas the pressor effects of increasing doses of
      norepinephrine were potentiated by L-NNA, those of angiotensin II were not
      affected, which implied that NO was selectively involved in modulating the
      pressor effect of norepinephrine. To explore the mechanisms involved in this
      potentiation, we examined the effect of L-NNA on the pressor effect of tyramine,
      a purely-indirectly-acting sympathomimetic amine which enters nerve terminals
      thorough uptake 1 and liberates norepinephrine from storage vesicles. Increasing
      doses of tyramine produced pressor effects which, in contrast to those of
      norepinephrine, were significantly attenuated by pre-treatment with L-NNA.
      Similarly, pretreatment with cocaine, the classical inhibitor of uptake 1,
      significantly decreased the pressor effect of tyramine; however, the response to
      tyramine was then restored when L-NNA was administered, thus reversing the effect
      of cocaine. We conclude that NO plays a major role in the adrenergic system by
      enhancing the activity of uptake 1 in sympathetic nerve terminals. Blockade of
      uptake 1 by cocaine is also partly dependent on NO. The stimulus for the
      mobilization of the NO synthase pathway in adrenergic neurons and the subsequent
      steps involved in modulating uptake 1 deserve further exploration.

PMID- 21968137
TI  - Leptin attenuates cerebral ischemia/reperfusion injury partially by CGRP
      expression.
AB  - Ischemic stroke is a medical emergency triggered by a rapid reduction in blood
      supply to localized portions of the brain, usually because of thrombosis or
      embolism, which leads to neuronal dysfunction and death in the affected brain
      areas. Leptin is generally considered to be a strong and quick stress mediator
      after injuries. However, whether and how peripherally administered leptin
      performs neuroprotective potency in cerebral stroke has not been fully
      investigated. It has been reported that CGRP(8-37), an antagonist of the CGRP
      receptor, could reverse the protective effect of leptin on rats with CIP
      (caerulein-induced pancreatitis). However, the question remains: are leptin and
      CGRP associated in cerebral ischemia/reperfusion injury? The present study
      attempted to evaluate the relationship between CGRP expression and leptin
      neuroprotective effects (1mg/kg in 200 MUL normal saline, i.p.) on focal cerebral
      ischemia/reperfusion injury in mice and the protective effect of leptin (500
      MUg/L) on neurons during hypoxia/reoxygenation injury. Peripheral administration
      of leptin alleviated injury-evoked brain damage by promoting CGRP expression,
      improving regional cerebral blood flow, and reducing local infarct volume and
      neurological deficits. Furthermore, leptin also promoted bcl-2 expression and
      suppressed caspase-3 in vivo and vitro after injury. Administration of CGRP(8-37)
      (4 * 10(-8)mol/L) partly abolished the beneficial effects of leptin, and restored
      the normal expression levels of bcl-2 and caspase-3 in neurons, which indicated
      that leptin-induced protection of neurons was correlated with release of CGRP.
      These results indicate that the neuroprotective effect of leptin against cerebral
      ischemia/reperfusion injury may be strongly relevant to the increase of CGRP
      expression.

PMID- 21968138
TI  - Lysophosphatidic acid induces a migratory phenotype through a crosstalk between
      RhoA-Rock and Src-FAK signalling in colon cancer cells.
AB  - Lysophosphatidic acid (LPA) acts as a potent stimulator of tumorigenesis. Cell
      cell adhesion disassembly, actin cytoskeletal alterations, and increased
      migratory potential are initial steps of colorectal cancer progression. However,
      the role that LPA plays in these events in this cancer type is still unknown. We
      explored this question by using Caco-2 cells, as colon cancer model, and
      treatment with LPA or pretreatment with different cell signalling inhibitors.
      Changes in the location of adherent junction proteins were examined by
      immunofluorescence and immunoblotting. The actin cytoskeleton organisation and
      focal adhesion were analysed by confocal microscopy. Rho-GTPase activation was
      analysed by the pull-down assay, FAK and Src activation by immunoblotting, and
      cell migration by the wound healing technique. We show that LPA induced adherent
      junction disassembly, perijunctional actin cytoskeletal reorganisation, and
      increased cell migration. These events were dependent on Src, Rho and Rock
      because their chemical inhibitors PP2, toxin A and Y27632, respectively,
      abrogated the effects of LPA. Moreover, we showed that Src acts upstream of RhoA
      in this signalling cascade and that LPA induces focal adhesion formation and FAK
      redistribution and activation in confluent monolayers. Focal adhesion formation
      was also observed in the front of migrating cells in response to LPA, and Rock
      inhibitor abolished this effect. In conclusion, our findings show that LPA
      modulates adherent junction disassembly, actin cytoskeletal disorganisation, and
      focal adhesion formation, conferring a migratory phenotype in colon tumour cells.
      We suggest a functional regulatory cascade that integrates RhoA-Rock and Src-FAK
      signalling to control these events during colorectal cancer progression.

PMID- 21968139
TI  - Polymorphism of peroxisome proliferator-activated receptor gamma (PPARgamma)
      Pro12Ala in the Iranian population: relation with insulin resistance and response
      to treatment with pioglitazone in type 2 diabetes.
AB  - The peroxisome proliferator-activated receptor gamma (PPARgamma) has important
      effects on insulin sensitivity, obesity and diabetes. Pioglitazone improves
      insulin sensitivity by activating PPARgamma. In view of inter-individual
      variability in therapeutic response to pioglitazone, this study was designed to
      search for an association between type 2 diabetes mellitus and Pro12Ala single
      nucleotide polymorphism (SNP) in PPARgamma (SNP rs1801282) and to investigate
      whether these genetic variants affect pioglitazone response in an Iranian
      population. A total of 101 patients with type 2 diabetes were treated for 12
      weeks with pioglitazone (15 mg/day). Paraclinical parameters were measured before
      and after therapy. We genotyped 128 control participants without diabetes and all
      patients with type 2 diabetes. The Pro12Ala polymorphism in PPARgamma was
      detected with real-time PCR. The Ala allele was found in 7% of the control
      participants vs. 3% of those with type 2 diabetes (P=0.04). The genotypic
      frequencies of Pro/Ala were 14.06% in the former group vs. 5.94% in the latter
      (P=0.036). There were significant changes in some laboratory values and
      biochemical markers of insulin sensitivity after pioglitazone therapy. The
      Pro12Ala polymorphism was associated with significant changes in insulin-to
      glucose ratio after treatment (P=0.015 and P=0.005). Our findings suggest that in
      carriers of the 12Ala variant, pioglitazone significantly reduced the risk of
      type 2 diabetes, and in diabetic patients with the Pro12Ala genotype, the
      therapeutic response to treatment was better than in patients with the Pro12Pro
      genotype, although the difference between groups did not reach statistical
      significance.

PMID- 21968140
TI  - Involvement of the dopaminergic receptors of the rat basolateral amygdala in
      anxiolytic-like effects of the cholinergic system.
AB  - Cholinergic system stimulation in some parts of the brain may affect anxiety
      related behaviors. This system has many interactions with dopaminergic
      neurotransmission in the brain. We have studied the effect of cholinergic system
      activation in the basolateral amygdala on anxiety-related behaviors in adult male
      wistar rats using the acetylcholinesterase inhibitor physostigmine. Furthermore,
      the possible involvement of dopamine D(1) and D(2) receptors of basolateral
      amygdala in physostigmine induced effects has been evaluated. The elevated plus
      maze task was used to assess anxiety parameters and all drugs were delivered into
      basolateral amygdala via bilaterally implanted chronic cannulas. Physostigmine
      (20 MUg/rat) increased the percentage of open arm time (%OAT) and open arm
      entries (%OAE), revealing an anxiolytic-like effect. However, muscarinic receptor
      antagonist scopolamine (8 MUg/rat) decreased %OAT indicating anxiogenic-like
      effect. A sub-effective dose of scopolamine (2 MUg/rat) plus physostigmine
      decreased %OAT and %OAE in comparison to saline plus physostigmine (20 MUg/rat).
      Muscarinic receptor agonist pilocarpine (5 MUg/rat), dopamine D(1) receptor
      antagonist SCH23390 (1 MUg/rat) and dopamine D(2) receptor antagonist sulpiride
      (5 MUg/rat) significantly increased %OAT which may show anxiolytic-like effects
      of drugs. Sulpiride (5 MUg/rat) also increased %OAE parameter. Pre-treatment with
      SCH23390 (0.5 and 1 MUg/rat) or sulpiride (5 MUg/rat) blocked anxiolytic-like
      effect of physostigmine (20 MUg/rat). All drugs were devoid of any significant
      effect on locomotor activity. It is concluded that intra-basolateral amygdala
      administration of physostigmine has anxiolytic-like effects which may be via
      muscarinic mechanisms. Furthermore, dopaminergic system activation probably via
      dopamine D(1) and D(2) receptors is necessary for mediating anxiolytic-like
      effects of physostigmine.

PMID- 21968141
TI  - Distinct modulatory effects of 5-HT on excitatory synaptic transmissions in the
      nucleus tractus solitarius of the rat.
AB  - The second-order relay neurons in the nucleus tractus solitarius (NTS) receive
      numerous peripheral afferent inputs mainly from the vagus nerve. Their activity
      is modified by several neuromodulators and hence autonomic responses are properly
      regulated. Serotonin (5-HT) is an important candidate for such neuromodulators,
      since serotonergic inputs and distribution of 5-HT receptors are provided in the
      NTS. However, its mechanism of action remains unclear. To evaluate the
      serotonergic modulation of synaptic transmission, we examined the effects of 5-HT
      (1.0-10.0 MUM) on the solitary tract-evoked excitatory postsynaptic currents
      (eEPSCs) and spontaneously occurring EPSCs (sEPSCs) in the preselected second
      order neurons of the rat NTS. 5-HT concentration-dependently decreased the
      amplitude of eEPSCs, which was accompanied by an increase in paired-pulse ratio.
      The inhibitory effect of 5-HT was mimicked by alpha-methylserotonin and blocked
      by ketanserin. 5-HT had no effect on the inward current induced in the NTS
      neurons by topically applied alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic
      acid (AMPA). On the other hand, 5-HT increased the frequency of sEPCSs without
      effect on their amplitude. This excitatory effect of 5-HT was mimicked by 2
      methylserotonin and antagonized by ondansetron. The results suggest a dual
      modulation of the excitatory synaptic transmission by 5-HT in the NTS;
      presynaptic inhibition of the peripheral inputs synapsing to the relay neurons
      via 5-HT(2) receptors and presynaptic excitation of inputs from the intrinsic
      local network via 5-HT(3) receptors. These effects of 5-HT may provide important
      means of optimizing the autonomic responses mediated by the NTS network.

PMID- 21968142
TI  - Differential effects of subtype-specific nicotinic acetylcholine receptor
      agonists on early and late hippocampal LTP.
AB  - Brain nicotinic acetylcholine receptors are involved in several neuropsychiatric
      disorders, e.g. Alzheimer's and Parkinson's diseases, Tourette's syndrome,
      schizophrenia, depression, autism, attention deficit hyperactivity disorder, and
      anxiety. Currently, approaches selectively targeting the activation of specific
      nicotinic acetylcholine receptors are in clinical development for treatment of
      memory impairment of Alzheimer's disease patients. These are alpha4beta2 and
      alpha7 nicotinic acetylcholine receptor agonists which are believed to enhance
      cholinergic and glutamatergic neurotransmission, respectively. In order to gain a
      better insight into the mechanistic role of these two nicotinic acetylcholine
      receptors in learning and memory, we investigated the effects of the alpha4beta2
      nicotinic acetylcholine receptor agonist TC-1827 and the alpha7 nicotinic
      acetylcholine receptor partial agonist SSR180711 on hippocampal long-term
      potentiation (LTP), a widely accepted cellular experimental model of memory
      formation. Generally, LTP is distinguished in an early and a late form, the
      former being protein-synthesis independent and the latter being protein-synthesis
      dependent. TC-1827 was found to increase early LTP in a bell-shaped dose
      dependent manner, but did not affect late LTP. In contrast, the alpha7 nicotinic
      acetylcholine receptor partial agonist SSR180711 showed enhancing effects on both
      early and late LTP in a bell-shaped manner. Furthermore, SSR180711 not only
      increased early LTP, but also transformed it into late LTP, which was not
      observed with the alpha4beta2 nicotinic acetylcholine receptor agonist.
      Therefore, based on these findings alpha7 nicotinic acetylcholine receptor
      (partial) agonists appear to exhibit stronger efficacy on memory improvement than
      alpha4beta2 nicotinic acetylcholine receptor agonists.

PMID- 21968144
TI  - Proteome studies on liver tissue in a phenobarbital-induced rat model.
AB  - Many drugs may affect the activity of cytochrome P450 (CYP), which is a major
      source of adverse drug interactions (ADR). Phenobarbital (PB) is the typical
      inducer of cytochrome P450. The aim of our study was to determine the changes in
      the cytosolic proteins expression in rat liver at a protein level following
      induction of cytochrome P450. Firstly, we made a phenobarbital-induced cytochrome
      P450 rat model. The total cytosolic proteins were then extracted from rat liver
      tissue and separated by 2-D gel electrophoresis (2-DE). Differentially expressed
      spots were identified by MALDI-TOF/TOF tandem mass spectrometry followed by
      database searching. Eight differentially expressed proteins were identified and
      these proteins were found to be involved in protein degradation, oxidative
      stress, energy metabolism, biotransformation, and the synthesis of quinolinic
      acid (QUIN). These findings should provide useful information for research into
      the regulation of cytochrome P450 gene expression, drug metabolism and drug
      interaction.

PMID- 21968143
TI  - The effect of low-dose Continuous Erythropoietin receptor activator in an
      experimental model of acute Cyclosporine A induced renal injury.
AB  - The use of Cyclosporine A (CsA) as rejection prophylaxis following organ
      transplantation is limited by its nephrotoxicity. CsA induces renal damage that
      is associated with tubulo-interstitial injury and parenchymal sequestration of
      macrophages, perpetuating pro-inflammatory processes. Furthermore, CsA exerts a
      diabetogenic effect by damaging pancreatic islet cell integrity. Continuous
      Erythropoietin Receptor Activator (CERA) was shown to mediate tissue-protective
      and anti-inflammatory effects in various settings of organ injury. Here, we
      investigated the effect of low dose CERA in a model of CsA-induced renal and
      pancreatic injury. Rats were exposed to medium-dose CsA for 28 days. Low-dose
      CERA was given to the treatment group (CERA) (n=6) once per week vs. a CsA
      treated control group (CONTROL) (n=6). The effect of CERA on renal and pancreatic
      injuries was analyzed by organ function, histology, immunohistochemistry (CD68(+)
      macrophages, insulin), ELISA (TGF-beta1) and RT-PCR (TGF-beta1, Osteopontin, IL
      10). CsA induced functional kidney damage. Low dose CERA did not lead to improved
      kidney function in the treatment group. However, low dose CERA showed a trend
      toward upregulation of osteopontin accompanied by increased renal macrophage
      infiltration and enhanced parenchymal TGF-beta1 and IL-10 when compared to
      controls. Moreover, CERA treated animals showed amelioration of pancreatic islet
      cell injury. In this model of acute CsA-mediated renal injury, low dose CERA
      administration was associated with anti-inflammatory effects and preservation of
      pancreatic islet cell viability.

PMID- 21968145
TI  - Bacterial expression systems for recombinant protein production: E. coli and
      beyond.
AB  - Escherichia coli expression system continues to dominate the bacterial expression
      systems and remain to be the preferred system for laboratory investigations and
      initial development in commercial activities or as a useful benchmark for
      comparison among various expression platforms. Some new developments in
      overcoming its shortcomings are reviewed in this paper, including antibiotics
      free selection plasmids, extracellular production, and posttranslational
      modifications. The ability for E. coli to make mg glycosylated proteins promises
      even broader applications of the E. coli system in the future. Significant
      progresses have also been made over the past few years in alternative bacterial
      expression systems. Notably, the Lactoccocus lactis system has proven to be a
      viable choice for membrane proteins. Additionally, several Pseudomonas systems
      were developed and achieved product titers comparable to E. coli systems. Other
      bacterial systems such as Streptomyces, coryneform bacteria, and halophilic
      bacteria offer advantages in some niche areas, providing more choices of
      bacterial expression systems for recalcitrant proteins.

PMID- 21968146
TI  - Mammalian cell protein expression for biopharmaceutical production.
AB  - Mammalian cell expression has become the dominant recombinant protein production
      system for clinical applications because of its capacity for post-translational
      modification and human protein-like molecular structure assembly. While
      expression and production have been fully developed and Chinese hamster ovary
      cells are used for the majority of products both on the market and in clinical
      development, significant progresses in developing and engineering new cell lines,
      introducing novel genetic mechanisms in expression, gene silencing, and gene
      targeting, have been reported in the last several years. With the latest
      analytical methods development, more attention is being devoted towards product
      quality including glycol profiling, which leads to better understanding the
      impact of culture condition during production. Additionally, transient gene
      expression technology platform plays more important role in biopharmaceutical
      early development stages. This review focused on the latest advancements in the
      field, especially in active areas such as expression systems, glycosylation
      impact factors, and transient gene expression.

PMID- 21968147
TI  - Production of recombinant proteins by filamentous fungi.
AB  - The initial focus of recombinant protein production by filamentous fungi related
      to exploiting the extraordinary extracellular enzyme synthesis and secretion
      machinery of industrial strains, including Aspergillus, Trichoderma, Penicillium
      and Rhizopus species, was to produce single recombinant protein products. An
      early recognized disadvantage of filamentous fungi as hosts of recombinant
      proteins was their common ability to produce homologous proteases which could
      degrade the heterologous protein product and strategies to prevent proteolysis
      have met with some limited success. It was also recognized that the protein
      glycosylation patterns in filamentous fungi and in mammals were quite different,
      such that filamentous fungi are likely not to be the most suitable microbial
      hosts for production of recombinant human glycoproteins for therapeutic use. By
      combining the experience gained from production of single recombinant proteins
      with new scientific information being generated through genomics and proteomics
      research, biotechnologists are now poised to extend the biomanufacturing
      capabilities of recombinant filamentous fungi by enabling them to express genes
      encoding multiple proteins, including, for example, new biosynthetic pathways for
      production of new primary or secondary metabolites. It is recognized that
      filamentous fungi, most species of which have not yet been isolated, represent an
      enormously diverse source of novel biosynthetic pathways, and that the natural
      fungal host harboring a valuable biosynthesis pathway may often not be the most
      suitable organism for biomanufacture purposes. Hence it is expected that
      substantial effort will be directed to transforming other fungal hosts, non
      fungal microbial hosts and indeed non microbial hosts to express some of these
      novel biosynthetic pathways. But future applications of recombinant expression of
      proteins will not be confined to biomanufacturing. Opportunities to exploit
      recombinant technology to unravel the causes of the deleterious impacts of fungi,
      for example as human, mammalian and plant pathogens, and then to bring forward
      solutions, is expected to represent a very important future focus of fungal
      recombinant protein technology.

PMID- 21968148
TI  - Absence of APOL1 risk variants protects against HIV-associated nephropathy in the
      Ethiopian population.
AB  - BACKGROUND: Susceptibility to end-stage kidney disease (ESKD) among HIV-infected
      Americans of African ancestral heritage has been attributed to APOL1 genetic
      variation. We determined the frequency of the APOL1 G1 and G2 risk variants
      together with the prevalence of HIV-associated nephropathy (HIVAN) among
      individuals of Ethiopian ancestry to determine whether the kidney disease genetic
      risk is PanAfrican or restricted to West Africa, and can explain the previously
      reported low risk of HIVAN among Ethiopians. METHODS: We studied a cohort of 338
      HIV-infected individuals of Ethiopian ancestry treated in one Israeli and one
      Ethiopian center. We sought clinical evidence for HIVAN (serum creatinine >1.4
      mg/dl or proteinuria >30 mg/dl in a spot urine sample). Genetic analyses included
      the genotyping of the APOL1 G1 and G2 variants, and a panel of 33 genomic
      ancestry-informative markers. Statistical analysis compared clinical and genetic
      indices for HIV-infected individuals of Ethiopian ancestry and overall Ethiopians
      to those reported for HIV-infected African-Americans, overall African-Americans,
      West Africans and non-Africans. FINDINGS: Three (0.8%) of 338 HIV-infected
      patients of Ethiopian ancestry showed clinical criteria compatible with renal
      impairment. Two of these 3 patients also have severe poorly controlled diabetes
      mellitus. The third nondiabetic patient underwent renal biopsy which ruled out
      HIVAN. This absence of clinically apparent HIVAN was significantly different from
      that reported for African-Americans. The APOL1 G1 and G2 risk variants were
      found, respectively, in 0 and 2 (heterozygote state) of the 338 HIV-infected
      individuals. Global ancestry and the frequencies of the APOL1 G1 and G2 variants
      are not statistically different from their frequencies in the general Ethiopian
      population, but are significantly and dramatically lower than those observed
      among HIV-infected African-Americans, African-Americans and West Africans.
      INTERPRETATION: The coinciding absence of HIVAN and the APOL1 risk variants among
      HIV-infected individuals of Ethiopian ancestry support a Western rather than Pan
      African ancestry risk for ESKD, and can readily explain the lack of HIVAN among
      individuals of Ethiopian ancestry.

PMID- 21968149
TI  - What are self-generated actions?
AB  - The concept of self-generated action is controversial, despite extensive study of
      its neural basis. Why is this concept so troublesome? We analyse the concept of
      self-generated action as employed by Passingham, Bengtsson, and Lau (2010a,
      2010b). There are two definitions of self-generated action; as operant action and
      as underdetermined action. The latter draws on subjective experience. Experiments
      on action awareness suggest that experience may not be a good guide for defining
      self-generated action. Nevertheless, we agree with Passingham and colleagues that
      self-generated actions exist distinct from operant actions. But defining 'self
      generated' by the degree of involvement of an endogenous process risks regress.
      We sketch an alternative account of self-generated action that tries to avoid
      these problems to make self-generated actions accessible to experimental science.

PMID- 21968150
TI  - The eyes know what you are thinking: eye movements as an objective measure of
      mind wandering.
AB  - Paralleling the recent work by Reichle, Reineberg, and Schooler (2010), we
      explore the use of eye movements as an objective measure of mind wandering while
      participants performed a reading task. Participants were placed in a self
      classified probe-caught mind wandering paradigm while their eye movements were
      recorded. They were randomly probed every 2-3 min and were required to indicate
      whether their mind had been wandering. The results show that eye movements were
      generally less complex when participants reported mind wandering episodes, with
      both duration and frequency of within-word regressions, for example, becoming
      significantly reduced. This is consistent with the theoretical claim that the
      cognitive processes that normally influence eye movements to enhance semantic
      processing during reading exert less control during mind wandering episodes.

PMID- 21968152
TI  - Single site umbilical laparoscopic surgery. Preface.

PMID- 21968153
TI  - Instrumentation and equipment for single-site umbilical laparoscopic surgery.
AB  - The minimally invasive approach has become the preferred technique for many
      pediatric operations. Advances in instrumentation and equipment have allowed for
      the introduction of a new type of minimally invasive surgery: single-site
      umbilical laparoscopic surgery (SSULS). The ultimate goal of SSULS is to leave
      the patient with no visible scar. In this article, we describe an array of
      instruments and equipment that are used for SSULS and discuss some of the related
      controversies of SSULS in children.

PMID- 21968154
TI  - Single-site umbilical laparoscopic appendectomy.
AB  - Laparoscopic appendectomy has become the standard approach in most institutions
      for children with nonperforated appendicitis, and in many institutions for
      patients with perforated appendicitis. Because of public perception and continued
      surgical innovation, there has been an impetus to perform operations with fewer
      and fewer scars, ultimately moving toward "scarless" surgery. Improvements in the
      laparoscopic technique and instrumentation have led to multiple reports of
      appendectomy in children being performed by the use of a single-incision
      approach. Although this approach remains an unproven benefit compared with a
      traditional laparoscopic appendectomy, the pressures to adopt single-incision
      appendectomy will continue to increase. This article will review the background
      of laparoscopy for appendectomy, the introduction of the single-incision
      approach, available data and outcomes from current literature, and a description
      of our technique.

PMID- 21968151
TI  - Ablation of Iqgap2 protects from diet-induced hepatic steatosis due to impaired
      fatty acid uptake.
AB  - Long-chain fatty acids (LCFA) serve as structural components for membrane
      biogenesis and as primary energy sources during mitochondrial beta-oxidation
      reactions. Hepatic LCFA uptake is complex, with characteristics suggestive of a
      dual-kinetic model manifested by rapid (carrier-assisted/facilitated) and delayed
      (passive diffusional) phases. Our previous work using mice deficient of the
      Iqgap2 gene established a highly novel link between IQGAP2, a putative GTPase
      activating protein, and hepatocarcinogenesis. Now we report that Iqgap2
      deficiency also results in selective loss of the facilitated phase of hepatocyte
      LCFA uptake with preservation of the diffusional component. This molecular defect
      was seen in Iqgap2(-/-) hepatocytes of all ages studied (1-, 4-, 8-months). The
      loss of facilitated LCFA uptake protected against development of hepatic
      triglyceride accumulation in Iqgap2-deficient mice fed high-fat diet, consistent
      with a fundamental role in physiological fat partitioning. These phenotypic
      changes could not be explained by genetic loss of fatty acid processing proteins
      known to regulate lipid uptake or metabolic processing pathways. Iqgap2-deficient
      livers also displayed enhanced insulin sensitivity. CONCLUSION: These
      observations identify a novel property of the putative GTPase-activating protein
      IQGAP2 in LCFA uptake in vitro and in vivo, and implicate IQGAP2 in an
      intracellular signaling pathway necessary for functional fatty acid uptake, lipid
      processing, and, possibly, glucose homeostasis.

PMID- 21968155
TI  - Single-site umbilical laparoscopic cholecystectomy.
AB  - Until the mid-1980s, cholecystectomy was performed through a generous right upper
      abdominal incision. After the early reports from Europe and the United States on
      the safety and feasibility of laparoscopic cholecystectomy, the minimally
      invasive revolution began. This revolution has continued to the current time,
      where surgeons are attempting to perform minimally invasive procedures with less
      or no visible scarring. Cholecystectomy is ideally suited for the single-site
      umbilical laparoscopic approach to obviate the need for epigastric and
      supraumbilical incisions. This article will describe the single-site umbilical
      laparoscopic cholecystectomy, which has been performed at Children's Mercy
      Hospital since 2009. Also, the literature concerning this approach in adults and
      in children will be discussed. Finally, a prospective randomized trial comparing
      the single-site cholecystectomy with the traditional 4-port laparoscopic
      cholecystectomy will also be described.

PMID- 21968156
TI  - Single-site umbilical laparoscopic pyloromyotomy.
AB  - Laparoscopic pyloromyotomy was first reported 20 years ago. This technique uses a
      small umbilical incision and 2 small upper abdominal incisions. During the last 5
      years, this approach has become the preferred technique for many pediatric
      surgeons in the infant who needs a pyloromyotomy. Recently, with the advent of
      single-site umbilical laparoscopic surgery, this approach is being used for
      several common pediatric conditions, including pyloric stenosis. This article
      will describe the single-site approach used at the Children's Hospital of Alabama
      and the early outcomes from its use in a relatively small group of infants. An
      improvement in the cosmetic appearance of the abdominal wall with the single-site
      approach appears to be the primary reason for its use.

PMID- 21968157
TI  - Single-site umbilical laparoscopic splenectomy.
AB  - Laparoscopic splenectomy was first described in children in 1993. Since then, it
      has become a commonly performed procedure in children because of reduced
      discomfort and hospitalization and significantly improved cosmesis compared with
      the open approach. With the advent of single-site laparoscopic surgery, it is
      only natural that this approach be used for splenectomy. This article will
      describe the reasons that the single-site approach might be useful for
      splenectomy and also the technique used at the author's institution. Moreover, a
      brief review of the current literature in children will be presented.

PMID- 21968158
TI  - Single-site umbilical laparoscopic segmental small bowel resection.
AB  - The single-site umbilical laparoscopic approach to abdominal surgery has become
      an evolving trend over the past few years. These operations have some technical
      limitations attributable to the loss of instrument triangulation, crowding of
      instruments, loss of ergonomic movements, and the fact that the view of the
      telescope/camera is in-line with the working instruments. However, because the
      size of the umbilical incision is determined by the size of the lesion or segment
      of bowel being resected during a traditional laparoscopic bowel resection, these
      operations are perhaps the most suited procedures for this approach. In this
      review, the techniques and applications for single-site umbilical laparoscopic
      bowel resection in children will be discussed.

PMID- 21968159
TI  - The use of magnets with single-site umbilical laparoscopic surgery.
AB  - Single-site umbilical incision laparoscopic surgery (SSULS) is increasingly being
      used to treat a variety of childhood surgical diseases. Existing SSULS approaches
      have inefficient triangulation and poor ergonomics. In an effort to overcome
      these shortcomings, magnet-assisted laparoscopy was developed. Specialized
      magnetic graspers are introduced through a standard 12-mm port and are controlled
      by a powerful external magnet. This study is a retrospective analysis of all
      magnet-assisted laparoscopic operations performed at the Fundacion Hospitalaria
      Private Children's Hospital from September 2009 to January 2011. Outcomes include
      demographics, diagnosis, operative time, intraoperative complications, and
      conversion rates. Forty-four magnet-assisted laparoscopic operations were
      performed. The operations included 23 appendectomies, 8 cholecystectomies, 3
      Nissen fundoplications, 2 gastrojejunostomies, 2 splenectomies, 2 ovarian
      tumor/cyst resections, 1 retroperitoneal lymphangioma resection, 1 left
      adrenalectomy, 1 total abdominal colectomy and 1 pulmonary wedge resection. The
      mean operative times for the most commonly performed operations were 61 minutes
      for appendectomy and 93 minutes for cholecystectomy. The operations were
      classified as follows: Group I, adjunct to conventional laparoscopy (5
      operations); Group II, adjunct to multiple-access umbilical laparoscopy (11
      operations); and Group III, true single-port laparoscopy (28 operations). Among
      Group II/III operations, 6 operations required 1 additional port outside the
      umbilicus. No operations required more that 1 additional port, and no operations
      were converted to the open technique. There were no intraoperative complications.
      Magnet-assisted laparoscopic surgery is safe and effective in children. The use
      of magnetic graspers improves triangulation and ergonomics while reducing the
      number and size of abdominal incisions.

PMID- 21968160
TI  - The necessity for prospective evidence for single-site umbilical laparoscopic
      surgery.
AB  - During the past 10 years, the minimally invasive technique has become the
      standard approach for many thoracic, abdominal, and pelvic procedures in adults
      and children. We now know there are well-defined benefits to this approach.
      However, when it was introduced, the laparoscopic technique was quickly adopted
      without appropriate clinical evidence to justify its advantages over open
      surgery. With continued efforts to increase the benefits of minimally invasive
      surgery for their patients, surgeons have developed new techniques to further
      decrease the trauma of the operation and improve the postoperative cosmetic
      appearance for the patient. These innovations range from decreasing the size of
      the ports and instruments to the current group of techniques termed "scarless"
      surgery. In today's era of evidence-based medicine, it is important to
      scientifically evaluate the benefits of a new approach or technique. This article
      seeks to review the history of laparoscopic surgery, apply lessons learned during
      the past 10 years to the evolution of single incision laparoscopic surgery, and
      urge for sound prospective evaluation for the use of laparoscopic surgery using a
      single umbilical incision.

PMID- 21968161
TI  - Optimal debulking surgery followed by paclitaxel/platinum chemotherapy is very
      effective in treating ovarian carcinosarcomas: a single center experience.
AB  - BACKGROUND: There have been only a few reports on the survival and management of
      patients with ovarian carcinosarcomas. We evaluated the clinical characteristics,
      outcomes and prognostic factors of ovarian carcinosarcomas. METHODS:
      Retrospective analysis of data obtained from medical records of 40 patients
      treated at the Asan Medical Center, Seoul, Korea, between January 1989 and
      January 2008. RESULTS: Median survival was significantly longer in patients <60
      years of age than in those >=60 (p = 0.001), patients with early-stage compared
      to advanced tumors (p = 0.035), those with optimally debulked tumors compared to
      suboptimally (p < 0.001) in the advanced stage, and patients treated with
      paclitaxel/platinum compared to patients treated with other chemotherapies (p <
      0.001). The progression-free interval was longer in patients with early-stage (p
      = 0.003) and optimally debulked tumors (p = 0.001), as well as in those treated
      with paclitaxel/platinum (p = 0.049). Multivariate analysis showed that advanced
      stage, non-optimal debulking and non-paclitaxel/platinum chemotherapy were
      significant independent predictors of a shorter progression-free interval, and
      that non-optimal debulking and non-paclitaxel/platinum chemotherapy were
      significant independent predictors of shorter overall survival. CONCLUSIONS:
      Early-stage optimal debulking and adequate chemotherapy can influence time to
      progression and survival, indicating that the most effective treatment for
      patients with ovarian carcinosarcomas consists of optimal debulking surgery
      followed by paclitaxel/platinum chemotherapy.

PMID- 21968162
TI  - Depth in box spaces.
AB  - Human observers adjust the frontal view of a wireframe box on a computer screen
      so as to look equally deep and wide, so that in the intended setting the box
      looks like a cube. Perspective cues are limited to the size-distance effect,
      since all angles are fixed. Both the size on  the screen, and the viewing
      distance from the observer to the screen were varied. All observers prefer a
      template view of a cube over a veridical rendering, independent of picture size
      and viewing distance. If the rendering shows greater or lesser foreshortening
      than the template, the box  appears like a long corridor or a shallow slab, that
      is, like a 'deformed' cube. Thus observers ignore 'veridicality'. This does not
      fit an 'inverse optics' model. We discuss a model of 'vision as optical user
      interface'.

PMID- 21968163
TI  - Primary plasmacytoma of the testicle: a case report.
AB  - INTRODUCTION: Extramedullary plasmacytoma is a rare plasma cell neoplasm.
      Plasmacytomas are most commonly found in the head and neck region, but can occur
      in many other locations. They rarely occur in the testis, and are commonly
      associated with concurrent multiple myeloma at the time of diagnosis. Isolated
      plasmacytoma of the testis is exceedingly rare, with few cases reported in the
      literature. CASE PRESENTATION: A 72-year-old Caucasian man presented with a
      painless testicular mass treated by orchiectomy. The mass was determined to be
      plasmacytoma on pathological examination. At the time of diagnosis, our patient
      did not have multiple myeloma, and is currently undergoing chemotherapy for
      treatment of his disease. CONCLUSION: Isolated plasmacytoma of the testicle is a
      rare cause of testicular mass, and is seldom reported in the literature. Patients
      with this disease require careful monitoring because of their high risk of
      progression to multiple myeloma. The diagnosis of testicular plasmacytoma can be
      challenging for primary care doctors and urologic specialists. This condition
      should be in the differential diagnosis in elderly men.

PMID- 21968164
TI  - Bowel obstruction with intestinal lipomatosis.

PMID- 21968165
TI  - Understanding retinopathy of prematurity: update on pathogenesis.
AB  - Retinopathy of prematurity (ROP), an ocular disease characterized by the onset of
      vascular abnormalities in the developing retina, is the major cause of visual
      impairment and blindness in premature neonates. ROP is a complex condition in
      which various factors participate at different stages of the disease leading to
      microvascular degeneration followed by neovascularization, which in turn
      predisposes to retinal detachment. Current ablative therapies (cryotherapy and
      laser photocoagulation) used in the clinic for the treatment of ROP have
      limitations and patients can still have long-term effects even after successful
      treatment. New treatment modalities are still emerging. The most promising are
      the therapies directed against VEGF; more recently the use of preventive dietary
      supplementation with omega-3 polyunsaturated fatty acid may also be promising.
      Other than pharmacologic and nutritional approaches, cell-based strategies for
      vascular repair are likely to arise from advances in regenerative medicine using
      stem cells. In addition to all of these, a greater understanding of other factors
      involved in regulating pathologic retinal angiogenesis continues to emerge,
      suggesting potential targets for therapeutic approaches. This review summarizes
      an update on the current state of knowledge on ROP from our and other
      laboratories, with particular focus on the role of nitro-oxidative stress and
      notably trans-arachidonic acids in microvascular degeneration, semaphorin 3
      operating as vasorepulsive molecules in the avascular hypoxic retina and in turn
      impairing revascularization, succinate and its receptor GPR91 in neuron-mediated
      retinal neovascularization, and omega-3 lipids as modulators of preretinal
      neovascularization.

PMID- 21968166
TI  - The expanding spectrum of viral anterior uveitis.

PMID- 21968167
TI  - Stroke and anti-VEGF therapy.

PMID- 21968168
TI  - Cataract surgery skill assessment.

PMID- 21968169
TI  - Floppy iris risk factors.

PMID- 21968171
TI  - Lens implant opacification.

PMID- 21968173
TI  - Phacotrabeculectomy meta-analysis.

PMID- 21968174
TI  - Ciliary body detachment.

PMID- 21968175
TI  - MacTel 2.

PMID- 21968178
TI  - Amsler grids for chloroquine toxicity.

PMID- 21968180
TI  - Hydroxychloroquine: lean body weight dosing.

PMID- 21968182
TI  - Sjogren-larsson syndrome.

PMID- 21968183
TI  - First Spanish HIV vaccine proves safe in phase I trials.

PMID- 21968184
TI  - Premature death rate in US is almost double that in France, study shows.

PMID- 21968185
TI  - DRESS with delayed onset acute interstitial nephritis and profound refractory
      eosinophilia secondary to Vancomycin.
AB  - BACKGROUND: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a
      relatively rare clinical entity; even more so in response to vancomycin. METHODS:
      Case report. RESULTS: We present a severe case of vancomycin-induced DRESS
      syndrome, which on presentation included only skin, hematological and mild liver
      involvement. The patient further developed severe acute interstitial nephritis,
      eosinophilic pneumonitis, central nervous system (CNS) involvement and worsening
      hematological abnormalities despite immediate discontinuation of vancomycin and
      parenteral corticosteroids. High-dose corticosteroids for a prolonged period were
      necessary and tapering of steroids a challenge due to rebound-eosinophilia and
      skin involvement. CONCLUSION: Patients with DRESS who are relatively resistant to
      corticosteroids with delayed onset of certain organ involvement should be treated
      with a more prolonged corticosteroid tapering schedule. Vancomycin is
      increasingly being recognized as a culprit agent in this syndrome.

PMID- 21968186
TI  - Copper handling by astrocytes: insights into neurodegenerative diseases.
AB  - Copper (Cu) is an essential trace element in the brain that can be toxic at
      elevated levels. Cu accumulation is a suspected etiology in several
      neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease,
      and prion-induced disorders. Astrocytes are a proposed depot in the brain for Cu
      and other metals, including lead (Pb). This article describes the physiological
      roles of Cu in the central nervous system and in selected neurodegenerative
      diseases, and reviews evidence that astrocytes accumulate Cu and protect neurons
      from Cu toxicity. Findings from murine genetic models of Menkes disease and from
      cell culture models concerning the molecular mechanisms by which astrocytes take
      up, store, and buffer Cu intracellularly are discussed, as well as potential
      mechanistic linkages between astrocyte functions in Cu handling and
      neurodegenerative diseases.

PMID- 21968187
TI  - Phosphorylation of LRP1 regulates the interaction with Fe65.
AB  - Neuronal Fe65 is a central adapter for the intracellular protein network of
      Alzheimer's disease related amyloid precursor protein (APP). It contains a unique
      tandem array of phosphotyrosine-binding (PTB) domains that recognize NPXY
      internalization motifs present in the intracellular domains of APP (AICD) and the
      low-density lipoprotein receptor-related protein LRP1 (LICD). The ternary
      APP/Fe65/LRP1 complex is an important mediator of APP processing and affects beta
      amyloid peptide production. Here we dissect by biochemical and biophysical
      methods the direct interactions within the ternary complex and reveal a
      phosphorylation-dependent insulin receptor substrate (IRS-) like interaction of
      the distal NPVY(4507) motif of LICD with Fe65-PTB1.

PMID- 21968188
TI  - p53 deacetylation by SIRT1 decreases during protein kinase CKII downregulation
      mediated cellular senescence.
AB  - Cellular senescence is thought to be an important tumor suppression process in
      vivo. We have previously shown that p53 activation is necessary for CKII
      inhibition-mediated cellular senescence. Here, CKII inhibition induced
      acetylation of p53 at K382 in HCT116 and HEK293 cells. This acetylation event was
      suppressed by SIRT1 activation. CKIIalpha and CKIIbeta were co-immunoprecipitated
      with SIRT1 in a p53-independent manner. Maltose binding protein pull-down and
      yeast two-hybrid indicated that SIRT1 bound to CKIIbeta, but not to CKIIalpha.
      CKII inhibition reduced SIRT1 activity in cells. CKII phosphorylated and
      activated human SIRT1 in vitro. Finally, SIRT1 overexpression antagonized CKII
      inhibition-mediated cellular senescence. These results reveal that CKII
      downregulation induces p53 stabilization by negatively regulating SIRT1
      deacetylase activity during senescence.

PMID- 21968189
TI  - Status and significance of CpG island methylator phenotype in endometrial cancer.
AB  - BACKGROUND: Endometrial cancer is a common gynecologic malignant disease, but
      patients with advanced disease have a poor prognosis. The CpG island methylator
      phenotype (CIMP) involves hypermethylation targeted toward the promoters of
      multiple genes. OBJECTIVE: To investigate the role of epigenetic aberration of
      tumor-related genes in endometrial cancer. METHODS: The promoter methylation
      status of 5 genes was examined in 35 endometrial cancer tissues, 15 matched
      adjacent normal endometrial tissues (NET) from the same cancer patients, and 22
      benign endometria from unaffected patients by methylation-specific PCR. CIMP
      positivity (CIMP+) was defined as concordant methylation of >=3 genes. RESULTS:
      The methylation frequency of promoters for the 5 genes in the cancer tissues
      ranged from 37% for P16 to 57% for P14. Cancer and benign endometria, but not
      cancer and adjacent NET, significantly differed in methylation of P14, P16, ER,
      COX-2 and RASSF1A (p < 0.05). CIMP+ was frequent in cancer and adjacent NET (46
      and 47%, respectively; p > 0.05), but absent in benign endometria. Moreover,
      CIMP+ was significantly correlated with methylation of P16 and COX-2 (r = 0.673
      and 0.662, respectively; p < 0.001). CONCLUSION: CIMP+ is an important and
      frequent epigenetic event in endometrial cancer or adjacent NET, and may be a
      biomarker for predicting early carcinogenesis. COX-2 is a good representative
      gene of CIMP+ in this cancer.

PMID- 21968190
TI  - Empirical evaluation reveals best fit of a logistic mutation model for human Y
      chromosomal microsatellites.
AB  - The rate of microsatellite mutation is dependent upon both the allele length and
      the repeat motif, but the exact nature of this relationship is still unknown. We
      analyzed data on the inheritance of human Y-chromosomal microsatellites in father
      son duos, taken from 24 published reports and comprising 15,285 directly
      observable meioses. At the six microsatellites analyzed (DYS19, DYS389I, DYS390,
      DYS391, DYS392, and DYS393), a total of 162 mutations were observed. For each
      locus, we employed a maximum-likelihood approach to evaluate one of several
      single-step mutation models on the basis of the data. For five of the six loci
      considered, a novel logistic mutation model was found to provide the best fit
      according to Akaike's information criterion. This implies that the mutation
      probability at the loci increases (nonlinearly) with allele length at a rate that
      differs between upward and downward mutations. For DYS392, the best fit was
      provided by a linear model in which upward and downward mutation probabilities
      increase equally with allele length. This is the first study to empirically
      compare different microsatellite mutation models in a locus-specific fashion.

PMID- 21968191
TI  - PPM-1, a PP2Calpha/beta phosphatase, regulates axon termination and synapse
      formation in Caenorhabditis elegans.
AB  - The PHR (Pam/Highwire/RPM-1) proteins are evolutionarily conserved ubiquitin
      ligases that regulate axon guidance and synapse formation in Caenorhabditis
      elegans, Drosophila, zebrafish, and mice. In C. elegans, RPM-1 (Regulator of
      Presynaptic Morphology-1) functions in synapse formation, axon guidance, axon
      termination, and postsynaptic GLR-1 trafficking. Acting as an E3 ubiquitin
      ligase, RPM-1 negatively regulates a MAP kinase pathway that includes: dlk-1, mkk
      4, and the p38 MAPK, pmk-3. Here we provide evidence that ppm-1, a
      serine/threonine phosphatase homologous to human PP2Calpha(PPM1A) and
      PP2Cbeta(PPM1B) acts as a second negative regulatory mechanism to control the dlk
      1 pathway. We show that ppm-1 functions through its phosphatase activity in a
      parallel genetic pathway with glo-4 and fsn-1 to regulate both synapse formation
      in the GABAergic motorneurons and axon termination in the mechanosensory neurons.
      Our transgenic analysis shows that ppm-1 acts downstream of rpm-1 to negatively
      regulate the DLK-1 pathway, with PPM-1 most likely acting at the level of pmk-3.
      Our study provides insight into the negative regulatory mechanisms that control
      the dlk-1 pathway in neurons and demonstrates a new role for the PP2C/PPM
      phosphatases as regulators of neuronal development.

PMID- 21968192
TI  - Sperm status regulates sexual attraction in Caenorhabditis elegans.
AB  - Mating behavior of animals is regulated by the sensory stimuli provided by the
      other sex. Sexually receptive females emit mating signals that can be inhibited
      by male ejaculate. The genetic mechanisms controlling the release of mating
      signals and encoding behavioral responses remain enigmatic. Here we present
      evidence of a Caenorhabditis elegans hermaphrodite-derived cue that stimulates
      male mating-response behavior and is dynamically regulated by her reproductive
      status. Wild-type males preferentially mated with older hermaphrodites. Increased
      sex appeal of older hermaphrodites was potent enough to stimulate robust response
      from mating-deficient pkd-2 and lov-1 polycystin mutant males. This enhanced
      response of pkd-2 males toward older hermaphrodites was independent of short
      chain ascaroside pheromones, but was contingent on the absence of active sperm in
      the hermaphrodites. The improved pkd-2 male response toward spermless
      hermaphrodites was blocked by prior insemination or by genetic ablation of the
      ceh-18-dependent sperm-sensing pathway of the hermaphrodite somatic gonad. Our
      work suggests an interaction between sperm and the soma that has a negative but
      reversible effect on a hermaphrodite-derived mating cue that regulates male
      mating response, a phenomenon to date attributed to gonochoristic species only.

PMID- 21968193
TI  - Environment-sensitive epigenetics and the heritability of complex diseases.
AB  - Genome-wide association studies have thus far failed to explain the observed
      heritability of complex human diseases. This is referred to as the "missing
      heritability" problem. However, these analyses have usually neglected to consider
      a role for epigenetic variation, which has been associated with many human
      diseases. We extend models of epigenetic inheritance to investigate whether
      environment-sensitive epigenetic modifications of DNA might explain observed
      patterns of familial aggregation. We find that variation in epigenetic state and
      environmental state can result in highly heritable phenotypes through a
      combination of epigenetic and environmental inheritance. These two inheritance
      processes together can produce familial covariances significantly higher than
      those predicted by models of purely epigenetic inheritance and similar to those
      expected from genetic effects. The results suggest that epigenetic variation,
      inherited both directly and through shared environmental effects, may make a key
      contribution to the missing heritability.

PMID- 21968194
TI  - A general mechanistic model for admixture histories of hybrid populations.
AB  - Admixed populations have been used for inferring migrations, detecting natural
      selection, and finding disease genes. These applications often use a simple
      statistical model of admixture rather than a modeling perspective that
      incorporates a more realistic history of the admixture process. Here, we develop
      a general model of admixture that mechanistically accounts for complex historical
      admixture processes. We consider two source populations contributing to the
      ancestry of a hybrid population, potentially with variable contributions across
      generations. For a random individual in the hybrid population at a given point in
      time, we study the fraction of genetic admixture originating from a specific one
      of the source populations by computing its moments as functions of time and of
      introgression parameters. We show that very different admixture processes can
      produce identical mean admixture proportions, but that such processes produce
      different values for the variance of the admixture proportion. When introgression
      parameters from each source population are constant over time, the long-term
      limit of the expectation of the admixture proportion depends only on the ratio of
      the introgression parameters. The variance of admixture decreases quickly over
      time after the source populations stop contributing to the hybrid population, but
      remains substantial when the contributions are ongoing. Our approach will
      facilitate the understanding of admixture mechanisms, illustrating how the
      moments of the distribution of admixture proportions can be informative about the
      historical admixture processes contributing to the genetic diversity of hybrid
      populations.

PMID- 21968195
TI  - What is the site of origin of cochleovestibular schwannomas?
AB  - The belief that cochleovestibular schwannomas arise from the glial-Schwann cell
      junction has repeatedly been quoted in the literature, although there is no
      published evidence that supports this statement. A systematic evaluation of the
      nerve of origin and the precise location of cochleovestibular schwannomas using
      our respective archival temporal bone collections was conducted. Forty tumors
      were within the internal auditory canal (IAC), while 10 were intralabyrinthine
      neoplasms. Of the 40 IAC schwannomas, 4 arose from the cochlear nerve, and 36
      from the vestibular nerve. Twenty-one tumors clearly arose lateral to the glial
      Schwann cell junction, while 16 tumors filled at least two thirds of the IAC,
      with the epicenter of the neoplasm located in the mid part or the lateral part of
      the IAC. Only 3 schwannomas were located in the medial one third of the IAC in
      the area of the glial-Schwann cell junction. We concluded that cochleovestibular
      schwannomas may arise anywhere along the course of the axons of the eighth
      cranial nerve from the glial-Schwann sheath junction up until their terminations
      within the auditory and vestibular end organs.

PMID- 21968196
TI  - A challenging, unpredictable world for people with autism spectrum disorder.
AB  - Autism is a pervasive neurodevelopmental disorder characterized by impairment of
      communication and social interaction, as well as by high levels of repetitive and
      ritualistic behaviours. This last dimension results in major difficulties in
      daily life: clinical reports of individuals with Autism Spectrum Disorder (ASD)
      show that they present tantrums as a response to change, or restricted interests
      and repetitive behaviours in order to prevent or minimize change. Such a crucial
      need to maintain sameness suggests substantial differences in how the ASD brain
      predicts the environment, and this might have a fundamental role in the deficit
      revealed in the highly unpredictable social world. Several lines of evidence
      indicating difficulties in generating or using predictions in ASD due to atypical
      information processing will be presented in this review. For instance, several
      studies have revealed that people with ASD demonstrate a unique profile of
      cognitive abilities, with strategies that depend to an abnormally large extent on
      sensory systems, at the expense of more integrative processing requiring an
      awareness of contextual subtleties necessary for prediction. At a more elementary
      level, patients with autism manifest unusual processing of unpredictable events,
      which might be rooted in a basic difference in how the brain orients to changing,
      novel sensory stimuli. This review presents results from ERPs and fMRI studies
      illustrating the psychophysiological mechanisms and neural bases underlying such
      phenomena in ASD. We propose that such dysfunction in the ability to build
      flexible prediction in ASD may originate from impaired top-down influence over a
      variety of sensory and higher level information processing, a physiopathological
      hypothesis which dovetails with the cortical under connectivity current theory.

PMID- 21968197
TI  - Infectious bursal disease virus-induced activation of JNK signaling pathway is
      required for virus replication and correlates with virus-induced apoptosis.
AB  - The Jun NH2-terminal kinase (JNK) which serves as an important component of
      cellular signal transduction pathways has been shown to regulate many viral
      infections. The present study demonstrated for the first time that infectious
      bursal disease virus (IBDV), the causative agent of a highly contagious disease
      in chickens, can activate JNK1/2 pathway in IBDV-infected cells dependent upon
      viral replication. IBDV-induced JNK1/2 activation causes its downstream target c
      Jun phosphorylation, which kinetically paralleled JNK1/2 activation.
      Investigations into the mechanism of JNK1/2 regulation revealed that inhibition
      of JNK1/2 activation leads to reduced viral progeny release, which is associated
      with decreased viral transcription and lower virus protein expression, and
      thereby limiting apoptotic cell death as evidenced by blockage of Bax activation,
      cytochrome c release, and caspase activation. These data suggest that the JNK
      pathway plays an important role in the IBDV replication and contributes to virus
      mediated changes in host cells.

PMID- 21968198
TI  - RNA segment 9 exists as a duplex concatemer in an Australian strain of epizootic
      haemorrhagic disease virus (EHDV): Genetic analysis and evidence for the presence
      of concatemers as a normal feature of orbivirus replication.
AB  - This paper reports a concatemeric RNA in a strain of epizootic haemorrhagic
      disease virus (EHDV) serotype 5. Sequencing showed that the concatemeric RNA
      contains two identical full-length copies of genome segment 9, arranged in
      series, which has apparently replaced the monomeric form of the segment. In vitro
      translation demonstrated that the concatemeric RNA can act as a viable template
      for VP6 translation, but that no double-sized protein is produced. Studies were
      also performed to assess whether mutations might be easily introduced into the
      second copy (which might indicate some potential evolutionary significance of a
      concatemeric RNA segment), however multiple (n=40) passages generated no changes
      in the sequence of either the upstream or downstream segments. Further, we
      present results that demonstrate the presence of concatemers or partial gene
      duplications in multiple segments of different orbiviruses (in tissue culture and
      purified virus), suggesting their generation is likely to be a normal feature of
      orbivirus replication.

PMID- 21968199
TI  - Effects of glycosylation on antigenicity and immunogenicity of classical swine
      fever virus envelope proteins.
AB  - Classical swine fever virus (CSFV) harbors three envelope glycoproteins (E(rns),
      E1 and E2). Previous studies have demonstrated that removal of specific
      glycosylation sites within these proteins yielded attenuated and immunogenic CSFV
      mutants. Here we analyzed the effects of lack of glycosylation of baculovirus
      expressed E(rns), E1, and E2 proteins on immunogenicity. Interestingly, E(rns),
      E1, and E2 proteins lacking proper post-translational modifications, most
      noticeable lack of glycosylation, failed to induce a detectable virus
      neutralizing antibody (NA) response and protection against CSFV. Similarly, no NA
      or protection was observed in pigs immunized with E1 glycoprotein. Analysis of
      E(rns) and E2 proteins with single site glycosylation mutations revealed that
      detectable antibody responses, but not protection against lethal CSFV challenge
      is affected by removal of specific glycosylation sites. In addition, it was
      observed that single administration of purified E(rns) glycoprotein induced an
      effective protection against CSFV infection.

PMID- 21968201
TI  - Ecological preferences of exophilic and endophilic ticks (Acari: Ixodidae)
      parasitizing wild carnivores in the Iberian Peninsula.
AB  - Ticks parasitizing wild carnivores and the tick-borne pathogens (TBPs) that they
      transmit may affect domestic carnivores and humans. Thus, investigating the role
      of wild carnivores as tick hosts is of relevance for understanding the life cycle
      of ticks in natural foci and the epidemiology of TBPs shared with domestic
      animals and humans. Therefore, the main objective of this study was to determine
      the ixodid tick fauna of wild carnivores in Peninsular Spain and the
      environmental factors driving the risk of wild carnivores to be parasitized by
      ixodid ticks. We hypothesized that the adaptation of tick species to differing
      climatic conditions may be reflected in a similar parasitization risk of wild
      carnivores by ticks between bioclimatic regions in our study area. To test this,
      we surveyed ixodid ticks in wild carnivores in oceanic, continental
      Mediterranean, and thermo-Mediterranean bioclimatic regions of Peninsular Spain.
      We analyzed the influence of environmental factors on the risk of wild carnivores
      to be parasitized by ticks by performing logistic regression models. Models were
      separately performed for exophilic and endophilic ticks under the expected
      differing influence of environmental conditions on their life cycle. We found
      differences in the composition of the tick community parasitizing wild carnivores
      from different bioclimatic regions. Modelling results partially confirmed our
      null hypothesis because bioclimatic region was not a relevant factor influencing
      the risk of wild carnivores to be parasitized by exophilic ticks. Bioclimatic
      region was however a factor driving the risk of wild carnivores to be parasitized
      by endophilic ticks. Spanish wild carnivores are hosts to a relevant number of
      tick species, some of them being potential vectors of pathogens causing serious
      animal and human diseases. Information provided herein can be of help to
      understand tick ecology in Spanish wildlife, the epidemiology of tick-borne
      diseases, and to prevent the risks of TBPs for wildlife, domestic animals, and
      humans.

PMID- 21968200
TI  - Use of Cre/loxP recombination to swap cell binding motifs on the adenoviral
      capsid protein IX.
AB  - We used Cre/loxP recombination to swap targeting ligands present on the
      adenoviral capsid protein IX (pIX). A loxP-flanked sequence encoding poly-lysine
      (pK-binds heparan sulfate proteoglycans) was engineered onto the 3'-terminus of
      pIX, and the resulting fusion protein allowed for routine virus propagation.
      Growth of this virus on Cre-expressing cells removed the pK coding sequence,
      generating virus that could only infect through alternative ligands, such as a
      tyrosine kinase receptor A (TrkA)-binding motif engineered into the capsid fibre
      protein for enhanced infection of neuronal cells. We used a similar approach to
      swap the pK motif on pIX for a sequence encoding a single-domain antibody
      directed towards CD66c for targeted infection of cancer cells; Cre-mediated
      removal of the pK-coding sequence simultaneously placed the single-domain
      antibody coding sequence in frame with pIX. Thus, we have developed a simple
      method to propagate virus lacking native viral tropism but containing cell
      specific binding ligands.

PMID- 21968202
TI  - The integration of the treatment for common mental disorders in primary care:
      experiences of health care providers in the MANAS trial in Goa, India.
AB  - BACKGROUND: The MANAS trial reported that a Lay Health Counsellor (LHC) led
      collaborative stepped care intervention (the "MANAS intervention") for Common
      Mental Disorders (CMD) was effective in public sector primary care clinics but
      private sector General Practitioners (GPs) did as well with or without the
      additional counsellor. This paper aims to describe the experiences of integrating
      the MANAS intervention in primary care. METHODS: Qualitative semi-structured
      interviews with key members (n = 119) of the primary health care teams upon
      completion of the trial and additional interviews with control arm GPs upon
      completion of the outcome analyses which revealed non-inferiority of this arm.
      RESULTS: Several components of the MANAS intervention were reported to have been
      critically important for facilitating integration, notably: screening and the
      categorization of the severity of CMD; provision of psychosocial treatments and
      adherence management; and the support of the visiting psychiatrist. Non-adherence
      was common, often because symptoms had been controlled or because of doubt that
      health care interventions could address one's 'life difficulties'. Interpersonal
      therapy was intended to be provided face to face by the LHC; however it could not
      be delivered for most eligible patients due to the cost implications related to
      travel to the clinic and the time lost from work. The LHCs had particular
      difficulty in working with patients with extreme social difficulties or alcohol
      related problems, and elderly patients, as the intervention seemed unable to
      address their specific needs. The control arm GPs adopted practices similar to
      the principles of the MANAS intervention; GPs routinely diagnosed CMD and
      provided psychoeducation, advice on life style changes and problem solving,
      prescribed antidepressants, and referred to specialists as appropriate.
      CONCLUSION: The key factors which enhance the acceptability and integration of a
      LHC in primary care are training, systematic steps to build trust, the passage of
      time, the observable impacts on patient outcomes, and supervision by a visiting
      psychiatrist. Several practices by the control arm GPs approximated those of the
      LHC which may partly explain our findings that they were as effective as the
      MANAS intervention arm GPs in enabling recovery.

PMID- 21968203
TI  - Hepatitis disease diagnosis using a novel hybrid method based on support vector
      machine and simulated annealing (SVM-SA).
AB  - In this study, diagnosis of hepatitis disease, which is a very common and
      important disease, is conducted with a machine learning method. We have proposed
      a novel machine learning method that hybridizes support vector machine (SVM) and
      simulated annealing (SA). Simulated annealing is a stochastic method currently in
      wide use for difficult optimization problems. Intensively explored support vector
      machine due to its several unique advantages is successfully verified as a
      predicting method in recent years. We take the dataset used in our study from the
      UCI machine learning database. The classification accuracy is obtained via 10
      fold cross validation. The obtained classification accuracy of our method is
      96.25% and it is very promising with regard to the other classification methods
      in the literature for this problem.

PMID- 21968204
TI  - An intelligent classifier for prognosis of cardiac resynchronization therapy
      based on speckle-tracking echocardiograms.
AB  - PURPOSE: Predicting response after cardiac resynchronization therapy (CRT) has
      been a challenge of cardiologists. About 30% of selected patients based on the
      standard selection criteria for CRT do not show response after receiving the
      treatment. This study is aimed to build an intelligent classifier to assist in
      identifying potential CRT responders by speckle-tracking radial strain based on
      echocardiograms. METHODS AND MATERIALS: The echocardiograms analyzed were
      acquired before CRT from 26 patients who have received CRT. Sequential forward
      selection was performed on the parameters obtained by peak-strain timing and
      phase space reconstruction on speckle-tracking radial strain to find an optimal
      set of features for creating intelligent classifiers. Support vector machine
      (SVM) with a linear, quadratic, and polynominal kernel were tested to build
      classifiers to identify potential responders and non-responders for CRT by
      selected features. RESULTS: Based on random sub-sampling validation, the best
      classification performance is correct rate about 95% with 96-97% sensitivity and
      93-94% specificity achieved by applying SVM with a quadratic kernel on a set of 3
      parameters. The selected 3 parameters contain both indexes extracted by peak
      strain timing and phase space reconstruction. CONCLUSIONS: An intelligent
      classifier with an averaged correct rate, sensitivity and specificity above 90%
      for assisting in identifying CRT responders is built by speckle-tracking radial
      strain. The classifier can be applied to provide objective suggestion for patient
      selection of CRT.

PMID- 21968205
TI  - Bayesian tracking of intracranial pressure signal morphology.
AB  - BACKGROUND: The waveform morphology of intracranial pressure (ICP) pulses holds
      essential informations about intracranial and cerebrovascular pathophysiological
      variations. Most of current ICP pulse analysis frameworks process each pulse
      independently and therefore do not exploit the temporal dependency existing
      between successive pulses. We propose a probabilistic framework that exploits
      this temporal dependency to track ICP waveform morphology in terms of its three
      peaks. MATERIAL: ICP and electrocardiogram (ECG) signals were recorded from a
      total of 128 patients treated for various intracranial pressure related
      conditions. METHODS: The tracking is posed as inference in a graphical model that
      associates a random variable to the position of each peak. A key contribution is
      to exploit a nonparametric Bayesian inference algorithm that offers robustness
      and real time performance. A simple, yet effective learning procedure estimates
      the statistical, nonlinear, dependencies between the peaks in a nonparametric way
      using evidence collected from manually annotated pulses. RESULTS: Experiments
      demonstrate the effectiveness of the tracking framework on real ICP pulses and
      its robustness to occlusion and missing peaks. On artificialy distorted ICP
      sequences, the average error in latency in comparision with MOCAIP detector was
      reduced as follows: 11.88-8.09 ms, 11.80-6.90 ms, and 11.76-7.46 ms for the
      first, second, and third peak, respectively. CONCLUSION: The proposed tracking
      algorithm sucessfuly increases the temporal resolution of detecting ICP pulse
      morphological changes from the minute-level to the beat-level.

PMID- 21968206
TI  - Synthesis, characterization and antimicrobial investigation of some moxifloxacin
      metal complexes.
AB  - The new complexes of moxifloxacin (MOX), with Ti(IV), Y(III), Pd(II) and Ce(IV)
      have been synthesized. These complexes were then characterized by melting point,
      magnetic studies and spectroscopic techniques involving infrared spectra (IR), UV
      Vis, (1)H NMR. C, H, N and halogen elemental analysis and thermal behavior of
      complexes also investigated. The results suggested that the molar ratio for all
      complexes is M: MOX=1:2 where moxifloxacin acts as a bidentate via one of the
      oxygen atoms of the carboxylate group and through the ring carbonyl group and the
      complexes have the following formula [Ti(MOX)(2)](SO(4))(2).7H(2)O,
      [Y(MOX)(2)Cl(2)]Cl.12H(2)O, [Pd(MOX)(2)(H(2)O)(2)]Cl(2).6H(2)O and
      [Ce(MOX)(2)](SO(4))(2).2H(2)O. The activation energies, E*, enthalpies, DeltaH*,
      entropies, DeltaS* and Gibbs free energies, DeltaG*, of the thermal decomposition
      reactions have been derived from thermogravimetric (TGA) and differential
      thermogravimetric (DrTG) curves, using Coats-Redfern (CR) and Horowitz-Metzger
      (HM) methods. The antimicrobial activity of these complexes has been evaluated
      against three Gram-positive and three Gram-negative bacteria and compared with
      the reference drug moxifloxacin. The antibacterial activity of Ti(IV) complex is
      significant for E. coli K32 and highly significant for S. aureus K1, B. subtilis
      K22, Br. otitidis K76, P. aeruginosa SW1 and K. oxytoca K42 compared with free
      moxifloxacin.

PMID- 21968207
TI  - Study of the interaction between bovine serum albumin and ZnS quantum dots with
      spectroscopic techniques.
AB  - The interaction between bovine serum albumin (BSA) and ZnS quantum dots (QDs) was
      studied by fluorescence, UV-vis spectroscopic techniques. The results showed that
      the fluorescence of BSA was strongly quenched by ZnS QDs and the quenching
      mechanism was discussed to be a static quenching procedure, which was proved by
      quenching rate constant K(q.) The recorded UV-vis data and the fluorescence data
      quenching by the QDs demonstrated that the interaction between them leads to the
      formation of QDs-BSA complex. Furthermore, the temperature effects on the
      structural and spectroscopic properties of individual QDs and protein and their
      bioconjugates (QDs-BSA) were also researched. It was found that, compared to the
      monotonically decrease of the individual QDs fluorescence intensity, the
      temperature dependence of the QDs-BSA emission had a much more complex behavior,
      highly sensitive to the conformational changes of the protein.

PMID- 21968209
TI  - Effect of nitro groups on the photo physical properties of benzimidazolone: a
      solvatochromic study.
AB  - Electronic absorption and fluorescence spectra of mono, di, and tri-nitro
      benzimidazolones are measured at room temperature (298 K) in nine solvents with
      different polarities and the observed shifts are compared with benzimidazolone.
      Ground and excited state electric dipole moments are determined using the
      solvatochromic method based on the bulk solvent properties, F(1)(epsilon, n) and
      F(2)(epsilon, n). A reasonable agreement is observed between the experimental and
      ab initio dipole moments. Change in dipole moment is also determined using the
      solvatochromic method based on the microscopic solvent polarity parameter,
      (E(T)(N)), which considers the polarization changes due to hydrogen bonding in
      different solvents. It has been observed that the correlation of the
      solvatochromic Stokes shifts with the parameter (E(T)(N)), is superior to that
      derived using bulk solvent polarity functions for all the benzimidazolones
      reported in the present study. Calculated difference between excited state and
      ground state dipole moments seems to be a good measure of the effect of nitro
      group when correlated with (E(T)(N)).

PMID- 21968208
TI  - Electronic spectra and photophysics of the alpha-carboline (1-azacarbazole)
      monomer.
AB  - The UV-vis electronic absorption and emission spectra of alpha-carboline or 1
      azacarbazole, 9H-pyrido[2,3-b]indole, AC, have been investigated in aprotic
      solvents. Radiative, k(r), non-radiative, k(nr), rate constants and natural
      lifetimes, tau(N), of the AC monomer in hexane and acetonitrile, obtained from
      the experimentally determined fluorescence quantum yields and fluorescence
      lifetimes, have been compared with those theoretically estimated. The closeness
      between these experimental and theoretical data, the small Stokes shifts, the
      mirror image relationship between the absorption and fluorescence spectra and the
      close correspondence between the absorption and fluorescence excitation spectra,
      provide good evidences that the emission of AC monomer occurs directly from its
      lowest singlet excited state. The mono- and multi-parametric analyses of the AC
      solvatochromism indicate that the polarity-polarizability, the hydrogen bond
      donor and the hydrogen bond acceptor properties of the solvent preferentially
      stabilize the singlet excited over the ground state. These analyses also reveal
      that photoexcitation reinforces the hydrogen bond donor and acceptor properties
      of the AC, becoming the pyridinic nitrogen atom more basic and the pyrrolic group
      more acid.

PMID- 21968210
TI  - Antagonistic properties of a natural product-Bicuculline with the gamma
      aminobutyric acid receptor: studied through electrostatic potential mapping,
      electronic and vibrational spectra using ab initio and density functional theory.
AB  - (+)-Bicuculline (hereinafter referred to as bicuculline), a phthalide
      isoquinoline alkaloid is of current interest as an antagonist of gamma
      aminobutyric acid (GABA). Its inhibitor properties have been studied through
      molecular electrostatic potential (MEP) mapping of this molecule and GABA
      receptor. The hot site on the potential surface of bicuculline, which is also
      isosteric with GABA receptor, has been used to interpret the inhibitor property.
      A systematic quantum chemical study of the possible conformations, their relative
      stabilities, FT-Raman, FT-IR and UV-vis spectroscopic analysis of bicuculline has
      been reported. The optimized geometries, wavenumber and intensity of the
      vibrational bands of all the conformers of bicuculline have been calculated using
      ab initio Hartree-Fock (HF) and density functional theory (DFT) employing B3LYP
      functional and 6-311G(d,p) basis set. Mulliken atomic charges, HOMO-LUMO gap
      DeltaE, ionization potential, dipole moments and total energy have also been
      obtained for the optimized geometries of both the molecules. TD-DFT method is
      used to calculate the electronic absorption parameters in gas phase as well as in
      solvent environment using integral equation formalism-polarizable continuum model
      (IEF-PCM) employing 6-31G basis set and the results thus obtained are compared
      with the UV absorption spectra. The combination of experimental and calculated
      results provides an insight into the structural and vibrational spectroscopic
      properties of bicuculline.

PMID- 21968211
TI  - Adaptation, isolation by distance and human-mediated transport determine patterns
      of gene flow among populations of the disease vector Aedes taeniorhynchus in the
      Galapagos Islands.
AB  - The black salt-marsh mosquito (Aedes taeniorhynchus) is the only native mosquito
      in the Galapagos Islands and potentially a major disease vector for Galapagos
      wildlife. Little is known about its population structure, or how its dynamics may
      be influenced by human presence in the archipelago. We used microsatellite data
      to assess the structure and patterns of A. taeniorhynchus gene flow among and
      within islands, to identify potential barriers to mosquito dispersal, and to
      investigate human-aided transport of mosquitoes across the archipelago. Our
      results show that inter-island migration of A. taeniorhynchus occurs frequently
      on an isolation by distance basis. High levels of inter-island migration were
      detected amongst the major ports of the archipelago, strongly suggesting the
      occurrence of human-aided transport of mosquitoes among islands, underlining the
      need for strict control measures to avoid the transport of disease vectors
      between islands. The prevalence of filarial nematode infection in Galapagos
      flightless cormorants is correlated with the population structure and migration
      patterns of A. taeniorhynchus, suggesting that A. taeniorhynchus is an important
      vector of this arthropod-borne parasite in the Galapagos Islands. Therefore
      mosquito population structure in Galapagos may have the potential to influence
      mosquito-borne parasite population dynamics, and the subsequent impacts of such
      pathogens on their host species in the islands.

PMID- 21968212
TI  - Morphological and molecular characterization of Neotropic Lymnaeidae (Gastropoda:
      Lymnaeoidea), vectors of fasciolosis.
AB  - Lymnaeidae play a crucial role in the transmission of fasciolosis, a disease of
      medical and veterinary importance. In the Neotropic, a region where fasciolosis
      is emergent, eight Lymnaeidae species are currently considered valid. However,
      our knowledge of the diversity of this taxon is hindered by the fact that
      lymnaeids exhibit extremely homogeneous anatomical traits. Because most species
      are difficult to identify using classic taxonomy, it is difficult to establish an
      epidemiological risk map of fasciolosis in the Neotropic. In this paper, we
      contribute to our understanding of the diversity of lymnaeids in this region of
      the world. We perform conchological, anatomical and DNA-based analyses (phylogeny
      and barcoding) of almost all species of Lymnaeidae inhabiting the Neotropic to
      compare the reliability of classic taxonomy and DNA-based approaches, and to
      delimitate species boundaries. Our results demonstrate that while morphological
      traits are unable to separate phenotypically similar species, DNA-based
      approaches unambiguously ascribe individuals to one species or another. We
      demonstrate that a taxon found in Colombia and Venezuela (Galba sp.) is closely
      related yet sufficiently divergent from Galba truncatula, G. humilis, G. cousini,
      G. cubensis, G. neotropica and G. viatrix to be considered as a different
      species. In addition, barcode results suggest that G. cubensis, G. neotropica and
      G. viatrix might be conspecifics. We conclude that conchological and anatomical
      characters are uninformative to identify closely related species of Lymnaeidae
      and that DNA-based approaches should be preferred.

PMID- 21968213
TI  - Severe neonatal hyperbilirubinemia and kernicterus: are these still problems in
      the third millennium?
AB  - Despite efforts to eliminate permanent and irreversible brain damage due to
      bilirubin encephalopathy and kernicterus, these conditions continue to accompany
      us into the third millennium. This phenomenon occurs not only in developing
      countries with emerging medical systems, but in Westernized countries as well.
      Comprehensive guidelines to detect newborns with jaundice and treat those in whom
      hyperbilirubinemia has already developed have been formulated in several
      countries, but have not been successful in completely eliminating the problem. In
      this appraisal of the situation we review selected aspects of bilirubin
      encephalopathy and/or kernicterus. We highlight recent reports of severe
      hyperbilirubinemia and kernicterus, discuss some of the factors responsible for
      the continuing appearance of these conditions, and briefly review what can be
      done to decrease bilirubin-related morbidity and mortality to the minimum.

PMID- 21968214
TI  - Public health and medical care for the world's factory: China's Pearl River Delta
      Region.
AB  - While the growth of urbanization, worldwide, has improved the lives of migrants
      from the hinterland, it also raises health risks related to population density,
      concentrated poverty and the transmission of infectious disease. Will megacity
      regions evolve into socially infected breeding grounds for the rapid transmission
      of disease, or can they become critical spatial entities for the protection and
      promotion of population health? We address this question for the Pearl River
      Delta Region (PRD) based on recent data from Chinese sources, and on the
      experience of how New York, Greater London, Tokyo and Paris have grappled with
      the challenges of protecting population health and providing their populations
      with access to health care services. In some respects, there are some important
      lessons from comparative experience for PRD, notably the importance of covering
      the entire population for health care services and targeting special programs for
      those at highest risk for disease. In other respects, PRD's growth rate and sheer
      scale make it a unique megacity region that already faces new challenges and will
      require new solutions.

PMID- 21968215
TI  - Hormone levels of male African striped mice change as they switch between
      alternative reproductive tactics.
AB  - Alternative reproductive tactics occur when individuals of the same species
      follow alternative ways to maximize reproductive success. Often younger and
      smaller males follow tactics that result in lower fitness than that of dominant
      larger males. The relative plasticity hypothesis predicts that hormone levels
      change as males change tactics, but direct tests of this hypothesis are missing.
      It has been demonstrated in a number of studies that males following different
      tactics also differ in hormone levels (unpaired data), but not that individual
      males change their hormone levels as they change tactic (paired data). We
      compared hormone levels in the same individuals before and after they changed
      their tactic, using field samples collected over a period of 6 years. We studied
      male striped mice (Rhabdomys pumilio) following three alternative reproductive
      tactics: 1. alloparental philopatric males; 2. solitary roaming males, and 3.
      group-living dominant breeders. Testosterone levels increased and corticosterone
      levels decreased when philopatric males became roamers or breeders. The increase
      in testosterone levels tended to be higher in philopatric males that became
      roamers than in philopatric males that became breeders. Testosterone levels
      decreased when roamers became breeders. Prolactin levels increased when males of
      any other tactic became breeders. Thus, males significantly changed their hormone
      profiles as they changed tactics. These results are in agreement with the
      hypothesis that changes in hormone levels are associated with the switch from one
      alternative reproductive tactic to another.

PMID- 21968216
TI  - Relationship between anorectal pressure and pelvic floor muscle tension in
      patients with pelvic floor organ prolapse accompanied by outlet obstruction.
AB  - OBJECTIVE: To investigate the value of anorectal manometry, combined with
      measuring pelvic floor muscle tension, to assess the anorectal dynamics of
      patients with pelvic floor organ prolapse accompanied by outlet obstruction.
      METHODS: 30 patients with pelvic floor organ prolapse and 30 healthy volunteers
      were included in the observation group. The relationships between anorectal
      pressure and pelvic floor muscle tension, the patients' subjective and objective
      symptoms, and posterior vaginal wall prolapse were analyzed in both groups.
      RESULTS: No significant difference was observed in the anorectal pressure between
      the observation group during straining to defecate and the control group (p =
      0.098). Statistically significant differences were found in the initial rectal
      sensory volume, the maximum tolerated volume, and the initial desire to defecate
      sensory volume between the two groups (p = 0.020, 0.001 and 0.035, respectively).
      A decrease in pelvic floor muscle tension was measured in the observation group
      (p = 0.037). Compared with the control group, the observation group exhibited
      decreased internal and external anal sphincter resting pressures, elevated rectal
      perception threshold, and reduced pelvic floor muscle tone. CONCLUSIONS:
      Anorectal manometry, combined with measuring pelvic floor muscle tension, can
      provide important references for diagnosing and assessing pelvic floor organ
      prolapse accompanied by outlet obstruction.

PMID- 21968217
TI  - Tertiary amines enhance reactions of organic contaminants with aqueous chlorine.
AB  - Through various anthropogenic inputs, tertiary amines can readily contaminate
      wastewater and drinking water sources and can form chlorammonium species
      (R(3)N(+)-Cl) during aqueous chlorine disinfection. This study investigated the
      less understood concept that these chlorammonium species can potentially enhance
      organic contaminant loss and increase disinfection byproduct formation to a
      greater extent than aqueous chlorine. Tertiary amines' effectiveness was highly
      dependent on amine structure as trimethylamine (TMA) and 4
      morpholineethanesulfonic acid (MES) enhanced organic contaminant loss, while
      others (nitrilotriacetic acid (NTA) and creatinine (CRE)) were ineffective. MES
      addition up to 25 MUM led to increased organic contaminant chlorination by up to
      three orders of magnitude while observing pseudo-first order kinetic behavior and
      a linear amine dose response. TMA addition up to 0.5 MUM accelerated organic
      contaminant chlorination by almost two orders of magnitude, but occasionally
      deviated from pseudo-first order kinetics with incomplete organic contaminant
      degradation and a non-linear amine dose response - a result linked to TMA's rapid
      auto-decomposition over time. Byproduct formation was identical with and without
      amine addition, and thus the chlorination mechanisms are likely similar to
      aqueous chlorine. Results from this study improve the mechanistic understanding
      behind tertiary amine-enhanced chlorination.

PMID- 21968218
TI  - Child with idiopathic pulmonary hemosiderosis: a case report from Pakistan with
      multiple ethical and moral issues.
AB  - This report discusses the case of a young Pakistani child diagnosed with
      idiopathic pulmonary hemosiderosis (IPH). The key features of IPH were iron
      deficiency anemia and pulmonary symptoms due to recurrent pulmonary hemorrhages.
      The child showed complications of the disease process because of late diagnosis.
      Because various ethical and moral issues were associated with the diagnosis and
      management of IPH, this case provides insights about the care burden of health
      care professionals and a child's parents in a Pakistani pediatric setting. During
      the course of the child's treatment at one of the private tertiary care settings
      of Karachi, Pakistan, the key challenges were as follows: declaring the diagnosis
      to the parents, dealing with the request of the child's parents for withdrawal of
      ventilatory support and withholding treatment, deciding the code status of the
      child, and ensuring the quality of the child's life after discharge from the
      hospital. It was learned from this case report that shared decision making and
      open communication with the child's family enabled the pediatric health care
      professionals to determine what was in the best interest of the child, resulting
      in provision of effective palliative care to the child. Moreover, it was realized
      that early detection of the disease and availability of hospice care can
      facilitate palliative care of children diagnosed with IPH.

PMID- 21968219
TI  - SLN mapping in colorectal cancer.

PMID- 21968221
TI  - Adjuvant zoledronic acid for breast cancer: mechanism of action?

PMID- 21968222
TI  - Zoledronic acid in early-stage breast cancer.

PMID- 21968223
TI  - Premature conclusions on HPV-only testing.

PMID- 21968225
TI  - Antioxidants and cancer.

PMID- 21968226
TI  - Differences between otolith- and semicircular canal-activated neural circuitry in
      the vestibular system.
AB  - In the last two decades, we have focused on establishing a reliable technique for
      focal stimulation of vestibular receptors to evaluate neural connectivity. Here,
      we summarize the vestibular-related neuronal circuits for the vestibulo-ocular
      reflex, vestibulocollic reflex, and vestibulospinal reflex arcs. The focal
      stimulating technique also uncovered some hidden neural mechanisms. In the
      otolith system, we identified two hidden neural mechanisms that enhance otolith
      receptor sensitivity. The first is commissural inhibition, which boosts
      sensitivity by incorporating inputs from bilateral otolith receptors, the
      existence of which was in contradiction to the classical understanding of the
      otolith system but was observed in the utricular system. The second mechanism,
      cross-striolar inhibition, intensifies the sensitivity of inputs from both sides
      of receptive cells across the striola in a single otolith sensor. This was an
      entirely novel finding and is typically observed in the saccular system. We
      discuss the possible functional meaning of commissural and cross-striolar
      inhibition. Finally, our focal stimulating technique was applied to elucidate the
      different constructions of axonal projections from each vestibular receptor to
      the spinal cord. We also discuss the possible function of the unique neural
      connectivity observed in each vestibular receptor system.

PMID- 21968227
TI  - Telehealth-delivered group smoking cessation for rural and urban participants:
      feasibility and cessation rates.
AB  - BACKGROUND: Large-group behavioral smoking cessation interventions are effective
      for helping people quit smoking, but have not been evaluated using
      videoconferencing technology for rural and remote participants who have no access
      to in-person cessation programs. The objectives of this study were to provide and
      evaluate an evidence-based group smoking cessation program for rural/remote
      smokers wishing to quit through a Telehealth videoconferencing link at their
      local Health Centre. METHODS: From September 2005 through April 2008, eight
      separate eight-session, 4 month long smoking cessation group programs were
      offered both in person to urban participants in Calgary and at up to six rural
      sites simultaneously via Telehealth videoconferencing. Quit rates were assessed
      at program completion, 6 and 12 month follow-up. Participants also provided
      evaluations of the program and technology. RESULTS: 554 smokers participated in
      the program: 370 in Calgary and 184 at various remote sites. Sixteen Telehealth
      sites participated from across Alberta and one site from the Northwest
      Territories. After program completion, continuous abstinence rates using the most
      conservative intent-to-treat method were 27.5% in Calgary and 25.5% for the rural
      Telehealth sites. Quit numbers were much higher using only Available Data at
      39.2% for Calgary and 37.2% for the rural sites. Similar rates were maintained
      over the 12-month follow-up. Program evaluations were positive. CONCLUSIONS: It
      is possible to offer effective smoking cessation to small groups of patients in
      rural or remote locations through Telehealth videoconferencing technology, which
      produces quit rates similar to in-person groups.

PMID- 21968228
TI  - Memory associations between negative emotions and alcohol on the lexical decision
      task predict alcohol use in women.
AB  - Implicit alcohol expectancies, or beliefs about alcohol which exist in the form
      of automatic memory associations, are thought to uniquely affect drinking
      behavior. Research also has indicated that there may be a distinctive
      relationship between negative reinforcement and alcohol use in women. However,
      the most common measures used to examine implicit alcohol cognitions may be
      insufficient to examine associations involving negative reinforcement. The
      current study utilized the Lexical Decision Task (LDT) to examine the
      relationship between implicit alcohol cognitions and reported drinking in a
      sample of college women. Seventy-eight female participants completed a LDT
      including alcohol- and emotion-words, questionnaire measures of explicit alcohol
      expectancies, and a measure of drinking behavior at baseline and after two
      months. Strong associations between negative emotion-words and alcohol-words (as
      measured by the LDT) were found to predict drinking at follow up, and to account
      for unique variance in drinking beyond the contribution of explicit measures. In
      addition, women who reported heavier drinking in response to social conflict on
      an explicit measure showed stronger priming of alcohol words by negative emotion
      words, thus implying that the LDT may tap into implicit cognitions related to
      alcohol use as a method of coping. These findings suggest that the LDT is
      sensitive to negative-reinforcement associations in a way that other measures are
      not.

PMID- 21968229
TI  - Maternal predictors of comorbid trajectories of cigarette smoking and marijuana
      use from early adolescence to adulthood.
AB  - This is the first study to examine maternal predictors of comorbid trajectories
      of cigarette smoking and marijuana use from adolescence to adulthood.
      Participants (N=806) are part of an on-going longitudinal psychosocial study of
      mothers and their children. Mothers were administered structured interviews when
      participants were adolescents, and participants were interviewed at six time
      waves, from adolescence to adulthood. Mothers and participants independently
      reported on their relationships when participants were X- age 14.1 years. At each
      time wave, participants answered questions about their cigarette and marijuana
      use from the previous wave to the present. Latent growth mixture modeling
      determined the participants' membership in trajectory groups of comorbid smoking
      and marijuana use, from X- ages 14.1 to 36.6 years. Multivariate logistic
      regression was used to assess the association of maternal factors (when
      participants were adolescents) with participants' comorbid trajectory group
      membership. Findings showed that most maternal risk (e.g., mother-child conflict,
      maternal smoking) and protective (e.g., maternal affection) factors predicted
      participants' membership in trajectory groups of greater and lesser comorbid
      substance use, respectively. Clinical implications include the importance of
      addressing the mother-child relationship in prevention and treatment programs for
      comorbid cigarette smoking and marijuana use.

PMID- 21968230
TI  - Depression among regular heroin users: the influence of gender.
AB  - The aim of this study was to determine the prevalence of recent (last 12 months)
      depression in regular young heroin users and to ascertain factors associated with
      depression in this population, broken down by gender. A sample of 561
      participants completed a cross-sectional survey. Eligibility criteria were: age
      30 years or younger, and having used heroin for at least 12 days in the last 12
      months and at least one day in the last 3 months. Participants were recruited
      outside of health-care facilities in the cities of Barcelona, Madrid and Seville
      by targeted sampling and chain referral methods. Depression was assessed using
      the World Mental Health Composite International Diagnostic Interview. The
      prevalence of recent depression was 22.3% (35.2% among women and 17.3% among men,
      p<0.001). In the multivariate analysis, the factors positively associated with
      recent depression in the whole sample were female gender, age 25 or less,
      inability to work due to health problems and high risk consumption of alcohol.
      Among woman, the related variables were age 25 or less, cocaine dependence in the
      last 12 months, and alcohol consumption in that period. Among men, employment
      status was the only related variable. Analysis of an overall sample without the
      gender breakdown may hide important differences in the factors associated with
      depression in men and women. Both prevention and treatment of depression should
      rely on specific gender analysis.

PMID- 21968232
TI  - Genome-wide association studies in Behcet's disease: expectations and promises.

PMID- 21968231
TI  - Conceptual and methodological challenges to measuring political commitment to
      respond to HIV.
AB  - BACKGROUND: Researchers have long recognized the importance of a central
      government's political "commitment" in order to mount an effective response to
      HIV. The concept of political commitment remains ill-defined, however, and little
      guidance has been given on how to measure this construct and its relationship
      with HIV-related outcomes. Several countries have experienced declines in HIV
      infection rates, but conceptual difficulties arise in linking these declines to
      political commitment as opposed to underlying social and behavioural factors.
      METHODS: This paper first presents a critical review of the literature on
      existing efforts to conceptualize and measure political commitment to respond to
      HIV and the linkages between political commitment and HIV-related outcomes. Based
      on the elements identified in this review, the paper then develops and presents a
      framework to assist researchers in making choices about how to assess a
      government's level of political commitment to respond to HIV and how to link
      political commitment to HIV-related outcomes. RESULTS: The review of existing
      studies identifies three components of commitment (expressed, institutional and
      budgetary commitment) as different dimensions along which commitment can be
      measured. The review also identifies normative and ideological aspects of
      commitment and a set of variables that mediate and moderate political commitment
      that need to be accounted for in order to draw valid inferences about the
      relationship between political commitment and HIV-related outcomes. The framework
      summarizes a set of steps that researchers can follow in order to assess a
      government's level of commitment to respond to HIV and suggests ways to apply the
      framework to country cases. CONCLUSIONS: Whereas existing studies have adopted a
      limited and often ambiguous conception of political commitment, we argue that
      conceiving of political commitment along a greater number of dimensions will
      allow researchers to draw a more complete picture of political commitment to
      respond to HIV that avoids making invalid inferences about the relationship
      between political commitment and HIV outcomes.

PMID- 21968235
TI  - The frequency of familial Mediterranean fever in an emergency unit.
AB  - Approximately 90% of patients with familial Mediterranean fever (FMF) complain of
      recurrent attacks of fever and abdominal pain of various severities. Prior to the
      diagnosis of FMF, the majority of patients are admitted to emergency units with a
      suspicion of acute abdomen pain and at least half of them undergo unnecessary
      abdominal interventions. The purpose of this study is to determine the frequency
      of FMF among the patients who are admitted to emergency units for acute abdominal
      pain. One hundred consecutive patients who were admitted to an emergency unit in
      Istanbul, Turkey, with acute abdominal pain were screened for FMF. When the
      definite cases were considered, a frequency of 2% was encountered which was
      significantly high compared to the frequency of FMF in Turkey. Physicians working
      in emergency units should include FMF in their differential diagnosis list when
      evaluating a patient with acute abdominal pain, especially in countries where the
      disease is prevalent.

PMID- 21968236
TI  - Characteristics of vascular involvement in Behcet's disease in Japan: a
      retrospective cohort study.
AB  - OBJECTIVES: We analysed the clinical vascular characteristics of Behcet's disease
      (BD) patients in Japan. METHODS: We retrospectively reviewed the clinical charts
      of 412 patients who fulfilled the 1987 Japanese criteria for BD and were treated
      in two University hospitals from July 1991 to December 2007. Patients with
      superficial thrombophlebitis were excluded, since it is categorised as a skin
      manifestation according to the Japanese criteria. RESULTS: Twenty-six patients
      (6%) had large-vessel involvement. Mean ages at BD diagnosis and onset of
      vascular episodes were 39.7 and 41.6 years, respectively. Males predominated
      (62%). Arterial and venous lesions were found in 8 (31%) and 21 patients (81%),
      respectively, including 3 (12%) with both types. Pulmonary artery occlusion was
      the most common arterial lesion (n=5, 19%), followed by ascending aortic aneurysm
      (n=2, 8%). Limb deep vein thrombosis was the leading venous lesion (n=20, 77%).
      Cardiac complications (angina pectoris/aortic regurgitation) occurred in two
      patients. Gastrointestinal involvement was more frequent than in patients without
      vascular involvement (p<0.001); ocular involvement was less frequent (p<0.05).
      Only 3 patients (12%) required surgery. Patients received prednisone and
      immunosuppressants, including infliximab, for vascular and/or concurrent
      gastrointestinal involvement. Nine patients received warfarin, without bleeding
      complications. One patient died during the observation period, 4 days after
      surgery for an aortic aneurysm. CONCLUSIONS: Frequency of vascular involvement in
      BD in Japan is lower than in other ethnic populations. Although one patient died
      during the observation, there was no fatal haemoptysis, even in patients
      receiving warfarin.

PMID- 21968238
TI  - Long-term remission of ocular and extraocular manifestations in Behcet's disease
      using infliximab.
AB  - OBJECTIVES: To investigate the long-term effect of infliximab on ocular and
      extraocular manifestations in patients with Behcet's disease. METHODS: Seven
      patients with active Behcet's disease and treated with infliximab at Aichi
      Medical University Hospital for more than 18 months were included in the study.
      We evaluated visual acuity, the average number of uveitis attacks involving the
      posterior segment, and general disease activity every 2 months. The Behcet's
      Disease Current Activity Form (BDCAF) was used for an overall index of disease
      activity. Anti-infliximab antibody levels were examined in the patients' sera.
      RESULTS: The follow-up period after initial introduction of infliximab ranged
      from 19 to 40 months (mean +/- SD, 32 +/- 8.7 months). The number of infliximab
      infusions ranged from 12 to 24 (19 +/- 4.4). By the 2-month follow-up, the
      frequency of uveitis attacks involving the posterior segment and the BDCAF scores
      were significantly improved compared to the 2 months before introducing
      infliximab. Anti-infliximab antibodies were detected in the sera of all examined
      patients. CONCLUSIONS: Significant long-term improvement in both the frequency of
      uveitis attacks involving the posterior segment and overall disease activity was
      provided by the administration of infliximab to patients suffering from Behcet's
      disease, despite the presence of anti-infliximab antibodies.

PMID- 21968237
TI  - Efficacy of adalimumab in patients with Behcet's disease unsuccessfully treated
      with infliximab.
AB  - OBJECTIVES: To evaluate the clinical response after switching from infliximab to
      adalimumab in patients with Behcet's disease (BD). METHODS: In this ongoing,
      prospective, longitudinal and observational study, data were collected on
      efficacy and safety of every patient with BD beginning anti-TNF therapy in the
      last 8 years. The present analysis was restricted to patients who were switched
      to adalimumab after failing or not tolerating infliximab. RESULTS: A total of 69
      patients with BD have been treated with infliximab so far. Seventeen of these
      (25%) have been switched to adalimumab for lack or loss of efficacy or infusion
      reactions. In 10 out of these 17, the main manifestations requiring switching
      were the mucocutaneous lesions, in 4 retinal vasculitis and in 3 the neurological
      involvement. Of the 17 treated patients, 9 showed sustained remission of the
      disease and 3 a good response. No side effects were observed in any patient.
      CONCLUSIONS: The results of our study suggest that patients with BD showing a
      scarce response or adverse events to infliximab may successfully be treated with
      adalimumab, regardless of the reason for switching.

PMID- 21968239
TI  - Mycophenolate mofetil as a novel immunosuppressant in the treatment of neuro
      Behcet's disease with parenchymal involvement: presentation of four cases.
AB  - OBJECTIVES: Behcet's disease is a multisystemic, relapsing, inflammatory disorder
      of unknown origin. Among Turkish cohorts, 5-15% of patients show involvement of
      the central nervous system (CNS) at some time during their disease. There are
      mainly two types of clinical presentation: parenchymal CNS inflammation
      manifesting mainly as meningoencephalitis of the brainstem, or dural sinus
      thrombosis. Several drugs like high-dose steroids or immunosuppressive agents,
      mainly azathioprine, are used in the treatment. For patients who do not respond
      sufficiently to these agents or are not able tolerate them, other options are
      needed. PATIENTS: We are presenting 4 cases with parenchymal neuro-Behcet's
      disease, where commonly used immunosuppressive drugs could not be continued due
      to intolerance or inefficacy. However, the patients benefited well from
      mycophenolate mofetil. The benefit was sustained during 3-7 years of follow-up
      (median 6.5 years). CONCLUSIONS: Mycophenolate mofetil seems to be an alternative
      drug in parenchymal neuro-Behcet's disease; however, large controlled studies
      should be performed for verification of our results.

PMID- 21968240
TI  - Surgical management of chylopericardium and chylothorax in a patient with
      Behcet's disease.
AB  - Behcet's syndrome is a chronic multisystem inflammatory disease characterised
      classically by recurrent oral and genital ulcers with ocular lesions. It can
      affect blood vessels of all sizes, but involves veins more commonly than arterie.
      The presence of chylothorax in Behcet's syndrome is rare, with only a few cases
      cited in the literature. The most likely pathogenesis is SVC thrombosis with
      obstruction of the orifice of the thoracic duct resulting in leakage of chyle
      from the pleural lymphatics into the pleural space. The majority of the
      previously reported cases were managed medically without surgical intervention.
      We believe that this report describes the first use of surgery to ligate the
      thoracic duct and create a pericardial window in a Behcet's syndrome with
      chylothorax and chylopericardium.

PMID- 21968241
TI  - Th17 cells in Behcet's disease: a new immunoregulatory axis.
AB  - Accumulating evidence suggests that the abnormality of innate and adaptive
      immunity responses plays an important role in Behcet's disease (BD). T helper
      (Th) cells have a central role in modulating immune responses. Traditionally, BD
      is regarded as a Th1-mediated inflammatory disease. Recently, Th17 cells were
      identified as a new subset of Th cells unrelated to Th1 or Th2 cells, and several
      cytokines are involved in regulating their activation and differentiation. Naive
      murine CD4+ Th can be induced to differentiate towards Th1, Th2, Th17 and Treg
      phenotypes according to the local cytokine milieu. The committed cells are
      characterised by expression of specific transcription factors, T bet for Th1,
      GATA-3 for Th2, Foxp3 for Tregs and RORgammat (RORgammat/RORC) for Th17 cells. It
      has been demonstrated that the skewing of murine Th towards Th17 and Treg is
      mutually exclusive. Th17 cells regulate inflammation via production of distinct
      cytokines such as interleukin (IL)-17. There is growing evidence that Th17 cells
      are pathological in many human autoimmune and inflammatory diseases, leading to
      intense interest in defining their origins, functions and developing strategies
      to block their pathological effects. Evidence from human disease such as BD
      suggests that specialised antigen-presenting cells drive their in vivo
      development. Knowledge of how Th17 cells interact with other immune cells is
      limited, but recent data suggest that Th17 cells may not be subject to strict
      cellular regulation by T regulatory cells. Notably, Th17 cells and Treg cells
      appear to share common developmental pathways and both cell types retain
      significant plasticity. Herein, we will discuss the molecular and cellular
      regulation of Th17 cells with an emphasis on BD. The identification of Th17 cells
      helps us to explain some of the anomalies seen in the Th1/Th2 axis and has
      broadened our understanding of the immunopathological effects of Th17 cells in
      the development of BD.

PMID- 21968242
TI  - Therapeutic approach to familial Mediterranean fever: a review update.
AB  - Familial Mediterranean fever (FMF) is a hereditary disorder characterised by
      recurrent attacks of fever with peritonitis or pleuritis, arthritis, myalgia or
      erysipelas-like skin lesions. The continuous inflammation in FMF is associated
      with increased serum amyloid A (SAA) protein which may lead to secondary
      amyloidosis and deposition of this insoluble protein in the kidney, gut, spleen,
      liver, heart etc. Therefore, treatment of patients with FMF is beneficial not
      only for the prevention of the acute attacks but also for improving their
      prognosis. In the present review we summarise the medical literature concerning
      FMF treatment, including new therapeutic agents and management of colchicine
      resistant patients. Three electronic databases (MEDLINE, EMBASE, and the Cochrane
      Library) were searched from 1 January 1960 to 28 February 2010 for any
      therapeutic approach to FMF, with MeSH headings and text words (Familial
      Mediterranean Fever, FMF treatment, colchicine, infliximab, anakinra, SSRI). In
      conclusion, colchicine remains the mainstay therapeutic option in FMF. It is
      effective in various manifestations of the disease such as fever, peritonitis and
      pleuritis. It prevents the development of amyloidosis. It is safe in humans
      regarding fertility, and can be used during pregnancy and nursing. Dose
      adjustment should be made in patients with renal or hepatic failure. It is less
      effective in arthritis or myalgia, requiring additional treatment with NSAIDs and
      steroids. In the few cases where FMF is resistant to colchicine other measures,
      including corticosteroids, non-biological and biological DMARDs, interferon alpha
      and SSRIs should be employed.

PMID- 21968244
TI  - De novo 7p partial trisomy characterized by subtelomeric FISH and whole-genome
      array in a girl with mental retardation.
AB  - Chromosome rearrangements involving telomeres have been established as one of
      the major causes of idiopathic mental retardation/developmental delay. This case
      of 7p partial trisomy syndrome in a 3-year-old female child presenting with
      developmental delay emphasizes the clinical relevance of cytogenetic diagnosis in
      the better management of genetic disorders. Application of subtelomeric FISH
      technique revealed the presence of interstitial telomeres and led to the
      ascertainment of partial trisomy for the distal 7p segment localized on the
      telomeric end of the short arm of chromosome 19. Whole-genome cytogenetic
      microarray-based analysis showed a mosaic 3.5 Mb gain at Xq21.1 besides the
      approximately 24.5 Mb gain corresponding to 7p15.3- > pter. The possible
      mechanisms of origin of the chromosomal rearrangement and the clinical relevance
      of trisomy for the genes lying in the critical regions are discussed.

PMID- 21968245
TI  - Benefits and harms of locking plate osteosynthesis in intraarticular (OTA Type C)
      fractures of the proximal humerus: a systematic review.
AB  - INTRODUCTION: Locking plate osteosynthesis of proximal humeral fractures are
      widely recommended and used, even in complex intraarticular fracture patterns
      such as AO/OTA Type C fractures. We systematically reviewed clinical studies
      assessing the benefits and harms of osteosynthesis with angle stable plates in
      AO/OTA Type C fractures of the proximal humerus. METHODS: We conducted an
      iterative search in PubMed, Embase, Cochrane Library, Web of Science, Cinahl, and
      PEDro in all languages from 1999 to November 2010. Eligible studies should study
      the outcome for Type C fractures after primary osteosynthesis with locking plate
      within two weeks of injury, and a follow-up period of six months or more.
      Patients should be evaluated with the Constant-Murley Score (CS). Two observers
      extracted data independently. RESULTS: Twelve studies and 282 Type C fractures
      were included. Results were categorised according to study type and synthesised
      qualitatively. No randomised clinical trials were identified. Two comparative,
      observational studies reported a mean CS of 71 (relative to contralateral
      shoulder) and 75 (non-adjusted Constant Score) for Type C fractures. For all
      studies mean non-adjusted CS ranged from 53 to 75. Mean age- and sex-adjusted CS
      ranged from 60 to 88. Mean CS relative to the contralateral shoulder ranged from
      71 to 85. The most common complications were avascular necrosis (range, 4-33%),
      screw perforations (range, 5-20%), loss of fixation (range, 3-16%), impingement
      (range, 7-11%) and infections range 4-19%. Reoperation rate ranged from 6 to 44%.
      CONCLUSIONS: Insufficient study designs and unclear reporting preclude safe
      treatment recommendations. Complication and reoperation rates were unexpected
      high. Based on the studies included we cannot routinely recommend the use of
      locking plates in AO/OTA Type C fractures.

PMID- 21968246
TI  - Identification of proteins interacting with lactate dehydrogenase in claw muscle
      of the porcelain crab Petrolisthes cinctipes.
AB  - Biochemical adaptation of enzymes involves conservation of activity, stability
      and affinity across a wide range of intracellular and environmental conditions.
      Enzyme adaptation by alteration of primary structure is well known, but the roles
      of protein-protein interactions in enzyme adaptation are less well understood.
      Interspecific differences in thermal stability of lactate dehydrogenase (LDH) in
      porcelain crabs (genus Petrolisthes) are related to intrinsic differences among
      LDH molecules and by interactions with other stabilizing proteins. Here, we
      identified proteins that interact with LDH in porcelain crab claw muscle tissue
      using co-immunoprecipitation, and showed LDH exists in high molecular weight
      complexes using size exclusion chromatography and Western blot analyses. Co
      immunoprecipitated proteins were separated using 2D SDS PAGE and analyzed by
      LC/ESI using peptide MS/MS. Peptide MS/MS ions were compared to an EST database
      for Petrolisthes cinctipes to identify proteins. Identified proteins included
      cytoskeletal elements, glycolytic enzymes, a phosphagen kinase, and the
      respiratory protein hemocyanin. Our results support the hypothesis that LDH
      interacts with glycolytic enzymes in a metabolon structured by cytoskeletal
      elements that may also include the enzyme for transfer of the adenylate charge in
      glycolytically produced ATP. Those interactions may play specific roles in
      biochemical adaptation of glycolytic enzymes.

PMID- 21968247
TI  - Use of primary radiotherapy for rectal cancer in the Netherlands between 1997 and
      2008: a population-based study.
AB  - AIMS: To describe variation in the utilisation rates of primary radiotherapy for
      patients with rectal cancer in the Netherlands, focusing on time trends and age
      effects. MATERIALS AND METHODS: Data on primary non-metastatic rectal cancer were
      derived from the population-based cancer registries of four comprehensive cancer
      centres (regions) in the Netherlands (1997-2008, n=13,055). RESULTS: An increase
      in the utilisation rate was noted for the four regions, from 37-46% in 1997 to 66
      76% in 2008, for both genders. This increase was found predominately for
      preoperative radiotherapy (from 13-31% to 58-67%) and (unsurprisingly) was most
      pronounced for stage T2-3 patients (from 9-27% to 68-80%). The probability of
      receiving radiotherapy decreased with age: the odds of receiving preoperative
      radiotherapy was reduced in patients aged 65 years and older, as well as the odds
      of receiving postoperative radiotherapy in those aged 75 years and older, which
      remained significant after adjustment for stage, gender and region. Regional
      differences persisted in multivariable analyses, i.e. the odds of receiving
      preoperative radiotherapy was reduced in two regions: odds ratio: 0.4 (95%
      confidence interval: 0.4-0.5) and 0.7 (0.6-0.8). The odds of receiving
      postoperative radiotherapy was significantly increased in these regions [odds
      ratio: 2.6 (2.2-3.2) and 1.6 (1.3-1.9), respectively] and reduced in another
      [odds ratio 0.8 (0.6-0.96)]. CONCLUSIONS: The utilisation rate of radiotherapy
      for rectal cancer increased significantly over time, particularly for
      preoperative radiotherapy and was most pronounced for T2-3 patients. Due to
      national multidisciplinary treatment guidelines, regional differences became
      limited in recent years after adjustment for age and stage of the disease. A low
      utilisation rate of radiotherapy was seen in women and elderly patients.

PMID- 21968248
TI  - Severe hypernatremic dehydration and metabolic acidosis due to neonatal
      intestinal microvillus inclusion disease.
AB  - Neonatal microvillus inclusion disease (MID) is a congenital secretory diarrhea
      diagnosed by morphological enterocyte abnormalities on histology. The secretory
      diarrhea associated with MID occurs within the first few hours of birth and is
      exacerbated by enteral feeding. Affected newborns will die of dehydration and
      acid-base disturbances if MID is not rapidly recognized and treated with massive
      intravenous fluid replacement and gut rest. We report a case of a 4-day-old
      neonate presenting with 18% weight loss, hypernatremic dehydration and metabolic
      acidosis. Despite aggressive fluid resuscitation (206 ml/kg for the first 24 h),
      the dehydration and metabolic acidosis were only minimally improved. The diapers
      were found soaked with clear, non-odorous fluid on repeated examinations.
      Persistent secretory diarrhea was suspected. Stool electrolytes analyses showed a
      high NaCl content typical of secretory diarrhea and intestinal biopsy with
      electron microscopy was diagnostic of MID.

PMID- 21968249
TI  - Overexpression of synthesized cephalosporin C acylase containing mutations in the
      substrate transport tunnel.
AB  - Cephalosporin C (CPC) acylase converts CPC into 7-aminocephalosporanic acid (7
      ACA) by single-step enzymatic catalysis. An optimized CPC acylase gene with
      substituted codons and a reduced GC content was artificially designed,
      synthesized and overexpressed in recombinant Escherichia coli. The synthetic CPC
      acylase (sCPCAcy) exhibited 2.3 times more CPC specific deacylation activity with
      substrate CPC than with substrate glutaryl-7-ACA (GL-7-ACA). Site-directed
      mutagenesis of the residues around the active center showed that not only the
      residues that were adjacent to the CPC D-alpha-aminoadipyl moiety, but also the
      residues that were in the substrate transport tunnel (Leu666, Ala675, Leu677),
      played crucial roles in catalysis as the ones locating in active center. Mutant
      sCPCAcy(Leu666Phe) and sCPCAcy(Leu677Ala) exhibited significantly reduced
      specific enzymatic activity, while mutant sCPCAcy(Ala675Gly) demonstrated
      enhanced activity. The specific activity of purified sCPCAcy and
      sCPCAcy(Ala675Gly) was 10.0 U/mg and 11.3 U/mg, respectively. The optimal CPC
      acylase productivity of mutant sCPCAcy(Ala675Gly) reached 5349 U/l after 24h in
      culture, which was a 35% increase over the activity of sCPCAcy.

PMID- 21968250
TI  - Determination of residual antiplatelet activity of clopidogrel before neuraxial
      injections.
AB  - BACKGROUND: Guidelines recommend discontinuation of clopidogrel for 7 days before
      a neuraxial injection, while other directives suggest that 5 days might be
      adequate. We examined the time course of antiplatelet activity after clopidogrel
      discontinuation in patients undergoing epidural injections. METHODS: Thirteen
      patients were studied at baseline, 3, 5, and 7 days after discontinuation of
      clopidogrel. P(2)Y(12) determinations were performed using the VerifyNow((r))
      assay (Accumetrics, San Diego, CA, USA), and clot closure times with stimulation
      by collagen/epinephrine and collagen/adenosine diphosphate using the PFA-100((r))
      (Platelet Function Analyzer, Siemens Diagnostics, Deerfield, IL, USA). Repeated
      measures ANOVA was used to evaluate P(2)Y(12) platelet reaction units, PFA-100
      closure times, and per cent P(2)Y(12) inhibition values. Wilcoxon's signed-rank
      test was used to compare the frequencies of >=30%, 11-29%, and <=10% platelet
      inhibition between the baseline and subsequent sampling points after
      discontinuation of clopidogrel. RESULTS: On day 3 after clopidogrel
      discontinuation, two subjects had >=30%, seven subjects had 11-29%, and four
      subjects had <=10% platelet inhibition; the corresponding numbers were 0, 3, and
      10 subjects on day 5 (P=0.04). There were no differences between the >=30%, 11
      29%, and <10% platelet inhibition groups between days 5 and 7 (0, 0, and 13
      subjects, P=1.0). PFA-ADP closure times were normal throughout the study period
      except in one patient. CONCLUSIONS: These findings support the recommendation
      that discontinuation of clopidogrel for 5 days allows >70% of platelet function
      and might be adequate before a neuraxial injection is performed.

PMID- 21968251
TI  - Transcrural coeliac plexus block simulated on 200 computed tomography images.
AB  - BACKGROUND: We previously reported a modified transcrural coeliac plexus block
      (tCPB) case, using parameters obtained from a pre-procedural computed tomography
      (CT) image of that patient for the subsequent tCPB under fluoroscopy. In this
      study, we performed the same tCPB simulation on 200 CT images to determine
      optimal needle placement parameters with a comparison to the classic technique.
      METHODS: On each CT image across the coeliac trunk, the tCPB was simulated on
      both sides with the needle trajectory placed between the vertebra and organs
      targeting the coeliac trunk. The distances of the needle entrance from the
      midline, the insertion angles, and depths were measured and analysed in the
      groups: laterality, gender, intra-abdominal condition, and coeliac-aortic
      vertebral (c-a-v) distribution. RESULTS: Thirty placements failed to avoid organ
      penetration. The left-sided placements required a shorter distance, 3.58 (1.02)
      cm, with a steeper angle, 84.1 degrees  (6.0 degrees ), than those for the right
      placements [7.04 (1.56) cm, 61.1 degrees  (6.2 degrees )] (P<0.00001). The
      shortest distances, 3.1 (0.8) cm, with the steepest angles, 87.7 degrees  (4.5
      degrees ), were seen in the patients whose c-a-v distributions were left-left
      located (P<0.00001). Males required longer distance for needle insertion
      (P<=0.05). Cancer patients required a shorter distance with a steeper angle for
      the right needle placements (P<0.05). CONCLUSIONS: Needle placement parameters
      for tCPB vary in laterality, gender, pathologies, and c-a-v distributions. We
      would advocate a simulated block on individual patient's CT image to obtain
      relevant measurements for subsequent tCPB, although a clinical outcome study is
      warranted.

PMID- 21968252
TI  - Pyrrolidine dithiocarbamate attenuates nuclear factor-KB activation,
      cyclooxygenase-2 expression and prostaglandin E2 production in human
      endometriotic epithelial cells.
AB  - BACKGROUND: The nuclear factor-kappaB (NF-kappaB) pathway activates many of the
      target genes that are critical to the initiation and establishment of
      endometriosis. We sought to examine the potential application of pyrrolidine
      dithiocarbamate (PDTC), a potent NF-kappaB inhibitor, in the treatment of
      endometriosis. METHODS: The phosphorylation of IkappaB, expression of nuclear p65
      protein and NF-kappaB DNA binding in endometriotic epithelial cells (EECs),
      endometriotic eutopic epithelial cells (EuECs) and normal epithelial cells (NECs)
      were detected by Western blot analysis and electrophoretic mobility shift assay.
      Cyclooxgenase-2 (COX-2) gene and protein expressions in EECs were measured by RT
      PCR and Western blot analysis. Prostaglandin E(2) (PGE(2)) production of EECs was
      measured by ELISA. RESULTS: PDTC in the absence or presence of tumor necrosing
      factor-alpha (TNF-alpha) showed stronger inhibitory effects on IkappaB
      phosphorylation, expression of nuclear p65 protein and NF-kappaB DNA-binding
      activity in EECs than in EuECs or NECs. Pretreatment of EECs with PDTC resulted
      in a dose-dependent reduction in the TNF-alpha-induced expressions of COX-2 at
      gene and protein levels, as well as a reduction of PGE(2) synthesis. CONCLUSION:
      PDTC may represent a novel therapeutic strategy for treatment of endometriosis.

PMID- 21968253
TI  - Mitogroup: continent-specific clusters of mitochondrial OXPHOS complexes based on
      nuclear non-synonymous polymorphisms.
AB  - OXPHOS polymorphisms are known to be population specific and to influence
      disease. Previous studies have focused on mtDNA polymorphisms. Based on a world
      sampling of 629 unrelated individuals, we have now studied the polymorphisms of
      the 80 genes encoding OXPHOS nuclear subunits. We have shown that (i) amino-acid
      replacement frequencies are significantly correlated with their pathogenicity
      probability, and (ii) populations can be distinguished based only on amino-acid
      replacements in nuclear encoded OXPHOS subunits. These results are congruent with
      the major mtDNA haplogroups, which suggests that OXPHOS complexes are different
      across the populations in both nuclear and in mitochondrial encoded subunits.

PMID- 21968254
TI  - Development and implementation of an international proficiency testing program
      for a neutralizing antibody assay for HIV-1 in TZM-bl cells.
AB  - Recent advances in assay technology have led to major improvements in how HIV-1
      neutralizing antibodies are measured. A luciferase reporter gene assay performed
      in TZM-bl (JC53bl-13) cells has been optimized and validated. Because this assay
      has been adopted by multiple laboratories worldwide, an external proficiency
      testing program was developed to ensure data equivalency across laboratories
      performing this neutralizing antibody assay for HIV/AIDS vaccine clinical trials.
      The program was optimized by conducting three independent rounds of testing, with
      an increased level of stringency from the first to third round. Results from the
      participating domestic and international laboratories improved each round as
      factors that contributed to inter-assay variability were identified and
      minimized. Key contributors to increased agreement were experience among
      laboratories and standardization of reagents. A statistical qualification rule
      was developed using a simulation procedure based on the three optimization rounds
      of testing, where a laboratory qualifies if at least 25 of the 30 ID50 values lie
      within the acceptance ranges. This ensures no more than a 20% risk that a
      participating laboratory fails to qualify when it should, as defined by the
      simulation procedure. Five experienced reference laboratories were identified and
      tested a series of standardized reagents to derive the acceptance ranges for pass
      fail criteria. This Standardized Proficiency Testing Program is the first
      available for the evaluation and documentation of assay equivalency for
      laboratories performing HIV-1 neutralizing antibody assays and may provide
      guidance for the development of future proficiency testing programs for other
      assay platforms.

PMID- 21968255
TI  - Phase II study of irinotecan plus S-1 combination for previously untreated
      advanced non-small cell lung cancer: Hokkaido Lung Cancer Clinical Study Group
      Trial (HOT) 0601.
AB  - OBJECTIVE: Platinum-free regimens can represent an alternative for advanced non
      small cell lung cancer (NSCLC) if similar efficacy is provided with better
      tolerability. This study evaluated the efficacy and safety of combined irinotecan
      and S-1 for chemotherapy-naive advanced NSCLC. METHODS: Chemotherapy consisted of
      4-week cycles of intravenous irinotecan (100 mg/m(2), days 1 and 15) and oral S-1
      (80 mg/m(2), days 1-14). The primary endpoint was response rate, while secondary
      endpoints were overall survival, progression-free survival (PFS), and safety.
      RESULTS: A total of 112 cycles was administered to 40 patients (median 3 cycles;
      range 1-6 cycles). Twelve patients showed partial response and 17 patients had
      stable disease, representing a response rate of 30% and a disease control rate of
      72.5%. Median survival time and median PFS were 16.1 and 4.8 months,
      respectively. Hematological toxicities of grade 3 or 4 were neutropenia (32.5%)
      and anemia (5.0%). The most common nonhematological toxicities of grade 3 or 4
      included diarrhea (15.0%) and anorexia (17.5%). Patients homo- or heterozygous
      for UGTA1A*6 tended to show a higher incidence of grade 3 diarrhea (p = 0.055).
      CONCLUSION: The combination of irinotecan and S-1 offers good efficacy and
      tolerability for previously untreated advanced NSCLC.

PMID- 21968256
TI  - Time-dependent exposures and the fixed-cohort bias.

PMID- 21968257
TI  - Effects of single-wall carbon nanotubes in human cells of the oral cavity: geno
      cytotoxic risk.
AB  - Single-wall carbon nanotubes (SWCNTs) are one of the most extensively produced
      carbon materials and the environmental, public and professional exposure is
      therefore dramatically increasing. Consequently the studies on bio-effects and
      safety of SWCNTs are highly needed. The goal of this study was investigate the
      effects in vitro of SWCNTs in cells of the oral cavity, never employed in this
      research field. We exposed human gingival fibroblasts to 50, 75, 100, 125, 150
      MUg/ml SWCNTs for 24 h and we investigated genotoxicity (Comet assay and
      micronucleus test), cytotoxicity, oxidative stress, as reactive oxygen species
      (ROS) generation, and stress response, as Heat shock protein 70 (Hsp70)
      expression. SWCNTs produced genotoxic effects at all doses, even if detected with
      different sensitiveness by the two tests, and at the two highest doses induced a
      strong decrease of the cell proliferation and cell survival, causing apoptosis
      too. Furthermore, we proved the ability of these nanomaterials to induce
      oxidative stress and Hsp70 expression. Finally, by inhibition of Hsp70
      expression, we demonstrated that this heat shock protein conferred protection
      against SWCNT geno-cytotoxicity.

PMID- 21968258
TI  - The relationship between mean pulmonary artery pressure and quality of life in
      patients with mitral stenosis.
AB  - OBJECTIVES: We aimed to evaluate echocardiography-guided hemodynamic determinants
      of quality of life (QoL) via the Medical Outcomes Study Short Form (SF-36)
      questionnaire in patients with mild to moderate mitral stenosis (MS). METHODS:
      Eighty consecutive patients with rheumatic MS, who were admitted to the
      outpatient department, were enrolled into the study upon obtaining informed
      consent. Forty age-sex-matched healthy individuals were enrolled as a control
      group. RESULTS: All subscale scores and total SF-36 scores were significantly
      lower in the patient group representing a worse QoL. In multivariable logistic
      regression analysis, only mean pulmonary artery pressure (OR 1.138, 95% CI 1.049
      1.234, p = 0.002) was found to be an independent predictor of poor QoL in
      patients with mild to moderate MS. CONCLUSION: During follow-up of MS patients
      before intervention, physicians should consider that mean pulmonary artery
      pressure is the main factor which influences the patients' QoL. In patients with
      MS, it seems that referral to intervention should consider components and
      derivatives of QoL.

PMID- 21968259
TI  - Laboratory tests on the impact of superabsorbent polymers on transformation and
      sorption of xenobiotics in soil taking 14C-imazalil as an example.
AB  - Due to water scarcity, the agricultural production in arid areas is dependent on
      a sustainable irrigation management. In order to optimize irrigation systems, the
      application of superabsorbent polymers (SAP) as soil amendments, frequently
      studied within the last years, may be an appropriate measure to enhance the water
      holding capacity and the plant-available water in poor arable soils. These
      persistent polymers are also able to reduce heavy metal and salt stress to crops
      by accumulating those inorganic compounds. However, the impact of SAP on fate and
      behavior of organic xenobiotics in soil is unknown. Therefore, transformation and
      sorption of the model substance 14C-imazalil were monitored without and with SAP
      amendment in silty sand and sand soil under laboratory conditions. Within the 100
      d incubation period, the transformation of 14C-imazalil was not substantially
      affected by the SAP amendment even though the microbial activity increased
      considerably. In the silty sand soil, extractable residues dropped from 90% to
      45% without and from 96% to 46% with SAP amendment. Non-extractable residues
      continuously increased up to 49% and 35% while mineralization reached 6% and 5%,
      respectively. In the sand soil, characterized by its lower microbial activity and
      lower organic carbon content, extractable residues merely dropped from 99% to 81%
      and from 100% to 85% while non-extractable residues increased from 2% to 14% and
      1% to 10%, respectively. Mineralization was lower than 2%. The increased
      microbial activity, usually promoting transformation processes of xenobiotics,
      was compensated by the enhanced sorption in the amended soils revealed by the
      increase of soil/water distribution coefficients (Kd) of 26 to 42 L kg(-1) for
      the silty sand and 6 to 25 L kg(-1) for the sand, respectively.

PMID- 21968260
TI  - Molecular comparison of the sampling efficiency of four types of airborne
      bacterial samplers.
AB  - In the present study, indoor and outdoor air samples were collected using four
      types of air samplers often used for airborne bacterial sampling. These air
      samplers included two solid impactors (BioStage and RCS), one liquid impinger
      (BioSampler), and one filter sampler with two kinds of filters (a gelatin and a
      cellulose acetate filter). The collected air samples were further processed to
      analyze the diversity and abundance of culturable bacteria and total bacteria
      through standard culture techniques, denaturing gradient gel electrophoresis
      (DGGE) fingerprinting and quantitative polymerase chain reaction (qPCR) analysis.
      The DGGE analysis indicated that the air samples collected using the BioStage and
      RCS samplers have higher culturable bacterial diversity, whereas the samples
      collected using the BioSampler and the cellulose acetate filter sampler have
      higher total bacterial diversity. To obtain more information on the sampled
      bacteria, some gel bands were excised and sequenced. In terms of sampling
      efficiency, results from the qPCR tests indicated that the collected total
      bacterial concentration was higher in samples collected using the BioSampler and
      the cellulose acetate filter sampler. In conclusion, the sampling bias and
      efficiency of four kinds of air sampling systems were compared in the present
      study and the two solid impactors were concluded to be comparatively efficient
      for culturable bacterial sampling, whereas the liquid impactor and the cellulose
      acetate filter sampler were efficient for total bacterial sampling.

PMID- 21968261
TI  - Cooperation of dendritic cells with naive lymphocyte populations to induce the
      generation of antigen-specific antibodies in vitro.
AB  - The production of monoclonal antibodies by hybridoma technology is dependent on
      lymphocytes taken from vertebrates which have to be immunized against the
      corresponding antigen. We present here our first experiments which should allow
      the replacement of this in vivo immunization step by an in vitro immunization
      procedure. This work provides new possibilities for the specific activation of
      immune cells in order to use them for the generation of antibodies which are not
      of murine origin. Bone marrow-derived dendritic cells were loaded with antigen
      and co-cultured with naive T and B lymphocytes of non-immunized mice. The
      interaction and activation of the different cell types were investigated by
      measuring the expression of specific cell surface markers, the release of
      activation-dependent interleukins and the secretion of antigen-specific
      antibodies. We could demonstrate that dendritic cells process and present antigen
      fragments and activate T cells, that T cells proliferate and release activation
      induced interleukins, and that B cells maturate under the influence of activated
      T cells and secrete antigen-specific antibodies.

PMID- 21968262
TI  - From population to HIV: the organizational and structural determinants of HIV
      outcomes in sub-Saharan Africa.
AB  - BACKGROUND: There exists no consistent explanation for why some countries are
      successful in combating HIV/AIDS and others are not, and we need such an
      explanation in order to design effective policies and programmes. Research
      evaluating HIV interventions from a biomedical or public health perspective does
      not always take full account of the historical and organizational characteristics
      of countries likely to influence HIV outcomes. The analysis in this paper
      addresses this shortcoming by testing the impact of organizational and structural
      factors, particularly those resulting from population interventions, on HIV
      outcomes at the country level in sub-Saharan Africa. METHODS: The primary
      independent variables are factors that originated from efforts to slow population
      growth: whether a country has a long-time affiliate of the International Planned
      Parenthood Federation and whether a country has a population policy. Additional
      structural factors likely to impact HIV outcomes include the level of wealth, the
      level of cultural fractionalization, and the former colonial power. The present
      study uses multivariate regression techniques with countries in sub-Saharan
      Africa as the unit of analysis, and four measures of success in addressing HIV:
      the change in prevalence between 2001 and 2009; the change in incidence between
      2001 and 2009; the level of overall antiretroviral coverage in 2009; and the
      level of antiretroviral coverage for prevention of vertical transmission in 2009.
      RESULTS: Countries with the greatest declines in HIV prevalence and incidence had
      older International Planned Parenthood Federation affiliates and had adopted
      population policies, even after controlling for age of epidemic, level of
      antiretroviral coverage, and funding for HIV. Population policies are also
      important predictors of levels of overall antiretroviral coverage and of coverage
      of HIV-positive pregnant women to prevent vertical transmission. Structural
      factors with significant impacts include wealth, cultural fractionalization and
      former colonial power. CONCLUSIONS: The organizational and structural context of
      African countries is strongly predictive of HIV outcomes. This finding implies
      that policy and programmatic efforts should be put towards strengthening existing
      organizations and perhaps even creating new ones. The fact that cultural
      fractionalization also influences HIV outcomes suggests that efforts must be put
      towards identifying ways to reach political consensus in diverse societies.

PMID- 21968263
TI  - Transcatheter arterial infusion with heated saline changes the vascular
      permeability of rabbit hepatic tumors.
AB  - RATIONALE AND OBJECTIVES: The vascular permeability of tumors can be changed by
      transarterial infusion heat, but the mechanisms remain unknown. The aim of this
      study was to analyze the underlying causes of changes in tumor vascular
      permeability after heated perfusion via two different modes. MATERIALS AND
      METHODS: Thirty rabbits with VX2 hepatic tumors were randomly divided into three
      groups of 10 rabbits each. The hepatic artery was selectively catheterized via a
      femoral approach, and unheated saline (control group) or heated saline (60
      degrees C) was then injected in either a continuous (transcatheter arterial
      continuous perfusion [TACP]) or a pulsed (transcatheter arterial pulsed perfusion
      [TAPP]) manner. Changes in vascular permeability in the tumors were assessed
      using the following markers and methods: (1) qualitative assessment by visual
      estimation on digital subtraction angiography performed after the heat infusion
      procedure on live animals and quantitative assessment by spectrophotometry using
      Evans blue dye extravasation on tumor and liver tissue after animals were
      sacrificed and (2) kinase domain receptor or vascular endothelial growth factor
      (VEGF), expressed in vascular endothelial cells, assessed by immunohistochemical
      staining, Western blot analysis, and reverse transcription polymerase chain
      reaction. RESULTS: Tumor staining increased in the TAPP group more than in the
      TACP group, but not in the control group, assessed on digital subtraction
      angiography. Extracted dye was higher in tumors in the TAPP group than in those
      in the TACP group; extracted dye in both groups was higher than in the control
      group. Kinase domain receptor protein and messenger ribonucleic acid expression
      were both higher in the TAPP group than in the TACP and control groups. VEGF
      protein expression was lower in the TAPP and TACP groups than in the control
      group, but VEGF messenger ribonucleic acid expression was higher in the TACP
      group than in the TAPP and control groups, and VEGF messenger ribonucleic acid
      expression was lower in the TAPP group than in the control group. CONCLUSIONS:
      The vascular permeability of rabbit VX2 tumors significantly increased after
      arterial pulsed heated infusion, and the protein kinase domain receptor may play
      a key role in this increase of tumor vascular permeability.

PMID- 21968264
TI  - Understanding and treating opioid addiction in a patient with cancer pain.

PMID- 21968265
TI  - Aging effect on pressure pain thresholds of head and neck muscles.
AB  - BACKGROUND AND AIMS: Aging implies a physiological decline in skeletal muscle
      mass and strength, pain perception, transmission and processing, causing pain
      thresholds to increase (presbyalgesia). This study compares the pressure pain
      thresholds (PPTs) of 18 head and neck muscles in groups of young and elderly
      subjects. METHODS: A cross-sectional study was conducted on 40 subjects, selected
      from a group of 97, referred for dental consultation. The inclusion criterion was
      subjects' age (from 20 to 30, and over 65 years). Exclusion criteria were all
      conditions which may alter PPTs. In two groups, A (young subjects; 10 men, 10
      women) and B (elderly subjects; 11 men, 9 women) PPTs were evaluated by one
      calibrated examiner with a Fischer algometer. Data are described with mean values
      +/- standard error and the 95% confidence interval. The Mann-Whitney test was
      used to compare PPT values between the two groups (alpha=0.05). RESULTS: There
      was a significant difference between the PPTs of group A and B, which were higher
      in the elderly group in all muscles except five. CONCLUSIONS: These preliminary
      data demonstrate that PPTs increase with aging in the muscles examined. Other
      confirmatory studies with a larger sample size are necessary.

PMID- 21968266
TI  - Institute of social justice and medicine: developing a think tank to promote
      policy formation.
AB  - The World Health Organization (WHO) defines health as a "resource for everyday
      living, not the objective of living"; however, worldwide, there remains an
      unmistakable inequity in level of health and access to healthcare. The WHO has
      published documents on financing health systems towards universal health coverage
      [1], promoting healthy life [2], improving performance of health systems [3], and
      enriching humanity [4], highlighting our shared responsibility towards improving
      both national and global health and access to healthcare. These documents also
      recognize that, despite our local and regional priorities, there is a global
      desire to develop international strategies to improve healthcare.   [1] WHO
      Report. Health systems financing and the path to universal coverage. 2010.
      http://www.who.int/bulletin/health_financing/en/index.html [2] WHO Report.
      Reducing risks, promoting healthy life. 2002.
      http://www.who.int/whr/2002/en/index.html [3] WHO Bulletin. Health systems:
      improving performance. 2000. http://www.who.int/whr/2000/en/index.html [4] WHO
      Bulletin. Conquering suffering, enriching humanity 1997.
      http://www.who.int/whr/1997/en/index.html.

PMID- 21968267
TI  - Short-term effect of radioactive iodine therapy on CXCL-10 production in Graves'
      disease.
AB  - PURPOSE: To observe the short-term dynamic change in serum CXC chemokine ligand
      10 (CXCL10) levels in patients with Graves' disease (GD) before and after iodine
      therapy and to analyze the relationship between CXCL10 levels and clinical
      disease indices. METHODS: ELISA was used to determine serum levels of CXCL10 in
      43 patients with GD shortly before radioiodine therapy and on days six, 14, and
      60, post-therapy. RESULTS: Patients with newly diagnosed GD showed significantly
      higher levels of serum CXCL10 compared with the control group (P < 0.01). The
      serum CXCL10 level increased slightly on day six after treatment of radioactive
      iodine (P < 0.01). There was no significant statistical difference in serum
      CXCL10 levels pre-treatment and on day 14 post-treatment. A significant reduction
      in serum CXCL10 level was observed on day 60 (P < 0.01). GD patients with
      exophthalmia showed higher serum CXCL10 level than GD patients without
      exophthalmia. No correlation was found between levels of CXCL10 and FT3, FT4 or
      TSH at any time point, but significant positive correlation was shown between
      thyroid peroxidase antibodies (TPOAb) and CXCL10 (r=0.50, P < 0.01). CONCLUSION:
      CXCL10 participates in the early inflammatory response after radioactive iodine
      therapy in patients with Graves' disease and shows a strong association with the
      autoimmune process.

PMID- 21968268
TI  - Correlation of new bone metabolic markers with conventional biomarkers in
      hemodialysis patients.
AB  - BACKGROUND: New bone metabolic markers have become available clinically for
      evaluating chronic kidney disease mineral and bone disorders (CKD-MBD). The aim
      of this study was to correlate these new bone metabolic markers with conventional
      markers in regular hemodialysis (HD) patients. METHODS: One hundred forty three
      HD patients underwent cross-sectional assessment. Two bone formation markers,
      bone-specific alkaline phosphatase (BAP) and osteocalcin (OC), and one bone
      resorption marker, amino-terminal telopeptides of type 1 collagen (NTx), were
      selected for study. RESULTS: Both circulating OC and NTx levels showed positive
      correlations with serum intact parathyroid hormone (iPTH) levels. The levels of
      NTx and OC showed a strongly positive correlation, although they are known to be
      markers of different aspects of bone metabolism: bone formation and resorption.
      Patients with high iPTH (>=300pg/mL) had significantly higher levels of all the
      three bone markers compared with patients with low or normal iPTH . CONCLUSION:
      Serum OC and NTx levels may be useful markers of serum iPTH levels for evaluating
      bone turnover in HD patients and may eventually prove useful in the management of
      patients with CKD-MBD.

PMID- 21968269
TI  - Myotoxic effects of levobupivacaine, bupivacaine and ropivacaine in a rat model.
AB  - AIM: The aim of this study is to histopathalogically compare the myotoxic effects
      of a single injection of levobupivacaine, bupivacaine and ropivacaine in rat
      skeletal muscle. MATERIALS AND METHODS: Rats received intramuscular injections of
      0.5% bupivacaine (Group B), 0.5% ropivacaine (Group R), 0.5% levobupivacaine
      (Group L), or 0.9% normal saline (Group SF) (30 rats/group). At two, 10 and 20
      days, 10 rats from each group were sacrificed and muscle samples were examined
      for myotoxic effects using hematoxylin-eosin staining under a light microscope.
      RESULTS: Muscle damage in Groups B, L and R was similar qualitatively. In samples
      taken two days after injection, the muscle damage in Group B was maximal [Damage
      score: 3.0 (2.0-3.0)], Group R had less damage than Group B [damage score: 2.0
      (2.0-3.0)] and the damage in Group L was minimal [Damage score: 1.0 (1.0-2.0)].
      In muscle samples taken 10 days after injection, there was no significant
      difference in muscle damage scores among Groups B, R and L. In muscle samples
      taken 20 days after injection, regeneration was complete, and muscle mass was
      histologically normal for each of the three groups (B, L and R). CONCLUSION:
      Levobupivacaine's myotoxic effect is qualitatively similar to that seen (and
      previously reported) with bupivacaine and ropivacaine. Levobupivacaine was found
      to be quantitatively less myotoxic than bupivacaine and ropivacaine after a
      single intramuscular injection, only two days after injection. Myonecrosis
      developed after a single intramuscular injection of local anesthetic but was
      completely regenerated by the 20th day after injection.

PMID- 21968270
TI  - miR-21 down-regulation promotes apoptosis and inhibits invasion and migration
      abilities of OVCAR3 cells.
AB  - PURPOSE: To investigate the influence of miR-21 down-regulation on cell
      proliferation, apoptosis, invasion and migration of ovarian papillary
      adenocarcinoma cell lines (OVCAR3). METHODS: Short-hairpin RNA (shRNA),
      specifically targeting miR-21, was constructed and transfected into OVCAR3 cells
      using the pSIREN-RetroQ linear vector (pSIREN-miR-21). The expression of miR-21
      was detected with stem-loop real-time RT-PCR in OVCAR3 cells. Cell proliferation
      and apoptosis were monitored using the MTT assay and flow cytometry,
      respectively. Cell migration and invasion were assessed using the transwell
      migration and scratch-wound assay, respectively. Western-bloting was used for
      PDCD4 protein expression. RESULTS: pSIREN-miR-21 suppressed miR-21 expression in
      OVCAR3 cells. miR-21 expression levels in pSIREN-miR-21 cells was 0.3 +/- 0.1,
      which was significantly lower when compared with pSIREN-miR-21-Neg and control
      groups (P < 0.01). Cell inhibition rate in the pSIREN-miR-21 group was higher
      than the control group (29.4% vs 9.0%, P < 0.01), as was the percentage of
      apoptotic and necrotic cells. By transwell migration assay, the number of cells
      migrating in the pSIREN-miR-21 group was significantly lower than in the control
      group. In addition, fewer cells were observed in the wounded area of the pSIREN
      miR-21 group following the scratch-wound assay. PDCD4 expression was increased in
      OVCAR-3 cells transfected by pSIREN-miR-21 compared with vector-control
      transfected cells. Moreover, the optical density of the transfected cells was
      significantly lower than the two control groups. CONCLUSION: Down-regulation of
      miR-21 dramatically increased apoptotic cell death and decreased cell
      proliferation, invasion and migration in OVCAR3 cells. MiR-21 may play an
      important role in the biological behaviors of epithelial ovarian carcinoma cells
      through negative control of the expression of PDCD4.

PMID- 21968271
TI  - Adiponectin/leptin ratio and metabolic syndrome in a Mexican American population.
AB  - OBJECTIVE: Adiponectin and leptin play critical roles in the development of
      Metabolic Syndrome (MetS). This study was designed to assess the feasibility of
      using circulating levels of adiponectin and leptin for the early diagnosis of
      MetS. METHODS: A cross-sectional study was performed using data from 367
      participants randomly selected from a well-characterized cohort of Mexican
      Americans living at the US-Mexico border. RESULTS: Significant differences in
      circulating levels of adiponectin and leptin were observed between males and
      females. Adiponectin/leptin correlated significantly with MetS in this
      population. A receiver-operator characteristic (ROC) analysis demonstrated that
      adiponectin/leptin showed a high sensitivity (70.9% for males, 78.9% for females)
      and specificity (90.2% for males and 69.8% for females) for the diagnosis of
      MetS, independent of BMI measurements. CONCLUSION: These data support the central
      role of adiponectin and leptin in MetS, and demonstrated that adiponectin/leptin
      can be used as a highly sensitive and specific biomarker for MetS.

PMID- 21968272
TI  - Correlation of synovial fluid HMGB-1 levels with radiographic severity of knee
      osteoarthritis.
AB  - PURPOSE: This study measured high-mobility group box 1 (HMGB-1) levels in serum
      and synovial fluid (SF) in patients with primary knee osteoarthritis (OA) and
      correlated these levels with radiographic disease severity. METHODS: Seventy
      eight OA patients and 30 controls were enrolled in this study. All OA patients
      were scored according to the Kellgren-Lawrence (KL) grading system. HMGB-1 levels
      were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: SF HMGB-1
      levels were significantly higher in knee OA patients, compared with controls (P <
      0.01). Moreover, SF HMGB-1 levels were positively associated with KL scores (P <
      0.01). Multinomial logistic regression demonstrated that the SF HMGB-1 level was
      an independent factor for radiographic severity of OA (P=0.002); however, serum
      HMGB-1 levels did not differ significantly between OA patients and controls and
      did not correlate with KL scores (P > 0.05). CONCLUSION: These results
      demonstrate that HMGB-1 levels in SF of knee OA patients are independently
      associated with radiographic disease severity.

PMID- 21968273
TI  - Vascular progenitor recruitment in critically ill patients with acute kidney
      injury.
AB  - PURPOSE: Endothelial-like vascular progenitor cells (VPCs) are blood-derived
      angiogenic precursors that can facilitate vascular repair. The mobilization of
      peripheral blood VPCs and their role in recovery were investigated in patients
      with acute kidney injury (AKI) in the intensive care unit (ICU) setting. METHODS:
      Blood samples were drawn on days 0, 3, 7 and 14 in 38 patients admitted to ICU:
      30 with AKI and in eight controls with normal renal function. Circulating VPC
      levels were quantified by the early outgrowth cell cluster-forming assay and/or
      by flow cytometry. RESULTS: AKI patients (16 males, mean age 62.4) were
      classified as Risk (R, n=5), Injury (I, n=11) and Failure (F, n=14) according to
      the RIFLE criteria. VPC clusters increased over time following the diagnosis of
      AKI (p < 0.01 for day 0 vs. day 14) while VPC clusters were higher at enrollment
      in control patients and decreased over time (p=0.02). Greater mobilization of
      VPCs occurred in patients with more severe AKI at enrollment (I and F categories
      compared with R, p=0.05). A trend towards greater mobilization of VPC clusters
      was observed in patients with improved renal function (p=0.07). CONCLUSION: Time
      dependent increases in circulating VPCs occur in critically ill patients with
      established AKI. Greater mobilization of VPCs may be associated with recovery of
      renal function, suggesting a potential role for VPCs in repair after kidney
      injury.

PMID- 21968274
TI  - Historical determinants of contemporary attributes of African descendants in the
      Americas: the androgen receptor holds the key.
AB  - It is hypothesised that seemingly disparate and unrelated phenomena clustering in
      persons of African descent living in the Americas such as outstanding sprinting
      ability and high prostate cancer incidence and mortality are in fact related and
      emerge from enhanced testosterone responsiveness in descendants of African slaves
      surviving the transatlantic trade in Africans. It is postulated that the ability
      to have survived the middle passage was positively correlated with greater
      responsiveness of the androgen receptor to its primary ligands
      dihydrotestosterone and testosterone, and that slaves possessing more responsive
      androgen receptors experienced a survival advantage engendered by the enhanced
      anabolic effects which accrued such as increased red cell mass and therefore
      greater oxygen carrying capacity and tissue oxygen delivery enabling these slaves
      to tolerate stifling conditions in the hull of the slave ship, increased lean
      muscle mass and therefore greater surface area to volume ratio resulting in
      easier ability to dissipate heat and remain cool, and increased skin thickness
      and sebum production resisting the macerating effect of lying in admixed bodily
      fluids below deck. These androgen effects as well as others would have produced a
      survival advantage under the severe selection pressure created by the inhumane
      and physiologically challenging circumstances under which the slaves were
      transported from the interior of the African continent and West Africa to the
      'New World'. This would result in a population shift favouring increased androgen
      receptor responsiveness in descendants of African slaves populating the Americas
      and a corresponding geographic and racial distribution of androgen related
      phenomena such as sprinting prowess and prostate cancer. African-Americans having
      the highest prostate cancer incidence rate and the Caribbean having the highest
      prostate cancer mortality rates in the world are consistent with this hypothesis
      as is the observation that the 10 fastest men and 9 fastest women of all time are
      exclusively the descendants of West African slaves who survived the middle
      passage. It is predicted that as yet undiscovered as well as known biological
      correlates of enhanced androgen receptor responsiveness such as relatively short
      CAG-repeats in the poly Q tail of exon 1 of the androgen receptor gene will be
      more prevalent among African-Americans and Afro-Caribbean peoples than among West
      Africans. It is also predicted that African-Americans and Afro-Caribbean peoples
      will have relatively shorter CAG-repeats in the androgen receptor gene compared
      to West Africans.

PMID- 21968276
TI  - Intraoperative malposition of pedicle probe or screws: a potential cause of the
      acceleration of degeneration in superior adjacent intervertebral disc.
AB  - Adjacent segment degeneration (ASD) is considered as a long-term complication of
      spinal fusion procedure. Numerous clinical studies have reported some factors
      related with ASD, but few could address the reason why the incidence of caudal
      ASD is significantly lower than that of cranial ASD. Because the pedicle of
      vertebral arch is closer to the superior endplate of vertebrea and its cranial
      intervertebral disc, there might be some possibilities of malpositions of pedicle
      probe or screws into the superior vertebral endplate or disc during the procedure
      of posterior intervertebral fusion. A number of evidences have showed that
      puncture of intervertebral disc will result in disc degeneration. Thus the
      authors put forward the hypothesis that intraoperative malposition of pedicle
      probe or screws might be a cause of ASD at cranial segments.

PMID- 21968275
TI  - Marinobufagenin and cyclic strain may activate endothelial NADPH oxidase,
      contributing to the adverse impact of salty diets on vascular and cerebral
      health.
AB  - Limited but provocative ecologic epidemiology suggests that dietary salt may play
      a central role in the genesis of not only of stroke, but also dementia, including
      Alzheimer's disease. Impairment of nitric oxide bioactivity in the cerebral
      microvasculature is a likely mediator of this effect. Salted diets evoke
      increased adrenal secretion of the natriuretic steroid marinobufagenin (MBG),
      which promotes natriuresis via inhibition of renal tubular Na+/K+-ATPase; this
      effect is notably robust in salt-sensitive rodent strains in which other
      compensatory natriuretic mechanisms are subnormally efficient. MBG-mediated
      inhibition of sodium pumps in vascular smooth muscle likely plays a role in the
      hypertension induced by salty diets in these rodents. However, salt sensitivity
      in humans is associated with increased vascular mortality and ventricular
      hypertrophy independent of blood pressure; this suggests that MBG may be
      pathogenic via mechanisms unrelated to blood pressure control. Indeed, recent
      evidence indicates that MBG, via interaction with alpha1 isoforms of the sodium
      pump, can activate various intracellular signaling pathways at physiological
      concentrations too low to notably inhibit pump activity. An overview of current
      evidence suggests the hypothesis that MBG - as well as the cyclic strain induced
      by hypertension per se - may induce endothelial oxidative stress by activating
      NADPH oxidase. If so, this could rationalize the increase in vascular and
      systemic oxidative stress observed in salt-sensitive rodents fed salty diets, or
      in rodents infused with MBG; moreover, if this effect is a particularly prominent
      determinant of oxidative stress in cerebrovascular endothelium, it might help to
      explain the virtual absence of stroke and dementia in low-salt societies. As a
      corollary of this hypothesis, it can be predicted that spirulina-derived
      phycobilins, which appear to mimic the physiological role of bilirubin as an
      inhibitor of NAPDH oxidase complexes, may have potential for ameliorating the
      adverse health impacts of MBG and of salty diets. Potassium-rich diets are also
      likely to be protective in this regard, as they should suppress MBG production
      via their natriuretic impact, while their stimulatory effect on sodium pump
      activity may exert a hyperpolarizing effect on plasma membranes that suppresses
      NADPH oxidase activity.

PMID- 21968277
TI  - Immunoplasticity--triggers of regulatory function.
AB  - Regulatory T cells (Tregs) as key players of the immune system are exposed to
      numerous triggers including exogenous and endogenous factors. Autonomous nerve
      activity, melatonin, hormones such as vitamin D and glucocorticoids as well as
      the exposure to sunlight and microorganisms shape our immunological profile. The
      complexity of this system is highlighted by the power of each single trigger but
      more impressive by influencing each others function and potentials directly and
      indirectly. However, while monocausal correlations of single triggers on Tregs
      have been studied at length, there is much less known about the impact of
      numerous coexistent triggers on the dynamics of Treg activity. It can be
      hypothesized that the dynamics of Treg activity plays a crucial role for the
      control of our immune system. Therefore it is of the utmost importance that a new
      translational, multi- and interdisciplinary approach finds its way into future
      research efforts, which should lead to a more comprehensive and holistic view on
      the complex immunoregulatory mechanisms and to act in the sense of public health.

PMID- 21968278
TI  - Gastric bypass surgery: improving psoriasis through a GLP-1-dependent mechanism?
AB  - Psoriasis is a common inflammatory skin disease and obesity constitutes a risk
      factor for the disease. Obese patients with psoriasis are often more difficult to
      treat and are at increased risk for dyslipidemia, diabetes, hypertension and
      cardiovascular disease. Case reports suggest that gastric bypass surgery in
      patients with psoriasis may result in complete remission of the disease. A
      substantial weight loss is achieved in the months following surgery, which is
      likely to reduce psoriasis symptoms and risk of comorbidities. Interestingly,
      however, it has been described that improvement of psoriasis is initiated
      immediately following surgery before any weight loss could have happened. We
      hypothesize that the glucose-lowering gut incretin hormone glucagon-like peptide
      1 (GLP-1) is responsible for this effect. The levels of GLP-1 have been shown to
      increase up to 20 times after gastric bypass surgery. This most likely
      contributes importantly to the acute remission of type 2 diabetes, which is often
      induced by gastric bypass operations. The hormone is not hypersecreted after the
      purely restrictive bariatric procedure gastric banding and no case reports exist
      on improvement in psoriasis following gastric banding. Intriguingly, recent
      studies describe that GLP-1 may convey anti-inflammatory effects in addition to
      its effects on glucose homeostasis. Also, GLP-1 reduces appetite and
      gastrointestinal motility including gastric emptying, which reduces food intake
      and leads to weight loss. Thus, both a direct anti-inflammatory effect of GLP-1
      as well as an indirect effect through weight loss could contribute to improvement
      in psoriasis. A potential involvement of GLP-1 in the remission of psoriasis
      observed after bariatric surgery offers exciting possibilities for research and
      eventually perhaps new ways of anti-psoriatic treatment.

PMID- 21968279
TI  - A pilot randomized, single-blind, placebo-controlled trial of traditional
      acupuncture for vasomotor symptoms and mechanistic pathways of menopause.
AB  - OBJECTIVE: The aim of this study was to conduct a pilot study for the feasibility
      of planning a definitive clinical trial comparing traditional acupuncture (TA)
      with sham acupuncture (SA) and waiting control (WC) on menopause-related
      vasomotor symptoms (VMS), quality of life, and the hypothalamic-pituitary-adrenal
      axis in perimenopausal and postmenopausal women. METHODS: Thirty-three
      perimenopausal and postmenopausal women with at least seven VMS daily were
      randomized to TA, SA, or WC. The TA and SA groups were given three treatments per
      week for 12 weeks. Outcomes included the number and severity of VMS, Menopause
      Specific Quality of Life Questionnaire, Beck Depression Inventory, Spielberg
      State-Trait Anxiety Instrument, Pittsburgh Quality Sleep Index, 24-hour urine
      cortisol and metabolites, and adrenocorticotropic hormone stimulation testing.
      RESULTS: Both the TA and SA groups demonstrated improved VMS trends compared with
      the WC group (Delta -3.5 +/- 3.00 vs -4.1 +/- 3.79 vs -1.2 +/- 2.4, respectively;
      P = 20) and significantly improved Menopause-Specific Quality of Life
      Questionnaire vasomotor scores (Delta -1.5 +/- 2.02 vs -1.8 +/- 1.52 vs -0.3 +/-
      0.64, respectively; P = 0.04). There were no psychosocial group differences. Exit
      24-hour urinary measures were lower in the TA versus the SA or WC group in total
      cortisol metabolites (4,658.9 +/- 1,670.9 vs 7,735.8 +/- 3,747.9 vs 5,166.0 +/-
      2,234.5, P = 0.03; respectively) and dehydroepiandrosterone (41.4 +/- 27.46,
      161.2 +/- 222.77, and 252.4 +/- 385.40, respectively; P = 0.05). The response
      data on adrenocorticotropic hormone stimulation cortisol also trended in the
      hypothesized direction (P = 0.17). CONCLUSIONS: Both TA and SA reduce VMS
      frequency and severity and improve VMS-related quality of life compared with WC;
      however, TA alone may impact the hypothalamic-pituitary-adrenal axis. This
      association is viewed as preliminary and hypothesis generating and should be
      explored in a large clinical trial.

PMID- 21968280
TI  - The effectiveness of a relaxation training program for women with preterm labour
      on pregnancy outcomes: a controlled clinical trial.
AB  - BACKGROUND: Prenatal maternal stress is associated with adverse birth outcomes.
      Few studies have been published on the effectiveness of relaxation techniques
      focusing on women with preterm labour. OBJECTS: The object of this study was to
      examine the effectiveness of a relaxation training program on pregnancy outcomes
      in women experiencing preterm labour. DESIGN: A single-blinded, controlled
      clinical trial was used. SETTINGS: The study was conducted in two hospitals. Both
      of the study hospitals located in northern Taiwan are also large teaching
      hospitals and share the same treatment protocols of preterm labour. PARTICIPANTS:
      Inclusion criteria were being pregnant and diagnosed with preterm labour,
      singleton, hospitalized at time of entry into the study, at gestation between 20
      and 34 weeks, and having a cervical dilatation of less than 3 cm. Exclusion
      criteria were if they had one or any combination of the following: antepartum
      hemorrhage, infection, hypertension, gestational diabetes mellitus, or
      immunologic disease. METHODS: The experimental group (n=68) participants received
      a mini mp3 player containing a 13-min relaxation audio program, which they were
      instructed to follow daily, while the control group (n=59) received only routine
      prenatal care. Pregnancy outcomes were obtained from medical charts after each
      woman gave birth. RESULTS: Survival analysis demonstrated that the experimental
      group had a significant pregnancy prolongation compared to the control group
      (p=0.048). Participants receiving the relaxation training program had a
      significant lower proportion of extreme preterm birth, a higher rate of not being
      admitted to a NICU, and a lower rate of stay days within 30 days when compared
      with the control group. No significant differences were found on pregnancy
      outcomes in terms of the rate of preterm birth, low birth weight, Apgar score at
      1 and 5 min, mode of birth, and perinatal mortality between the two groups.
      CONCLUSIONS: Relaxation training for women with preterm labour is effective in
      delaying of delivery and enhancing positive pregnancy outcomes. This relaxation
      intervention is cost-effective, noninvasive, and easily applicable in women with
      preterm labour.

PMID- 21968281
TI  - The potential role of combined antioxidant treatment on pancreas of STZ-diabetic
      mice.
AB  - In diabetes, cells and tissues are damaged due to the imbalance between
      production of free radicals and removal of them. The effective biologic
      antioxidants for oxidative stress such as alpha-lipoic acid, vitamin E and
      selenium are effective in diminishing oxidative damage such as membrane lipid
      peroxidation. The experiment aimed to investigate the oxidative stress occurring
      in mitochondrial and cytoplasmic fraction of pancreatic tissues in streptozotocin
      diabetic mice and the possible effects of alpha-lipoic acid + vitamin E +
      selenium combination on oxidative damage and antioxidative system by using
      microscopic and biochemical methods. The mice were divided into five groups.
      These groups were treated by citrate buffer, the solvents of the antioxidants,
      combined the antioxidants [alpha-lipoic acid (50 mg/kg), vitamin E (100 mg/kg),
      selenium (0.25 mg/kg)], streptozotocin (40 mg/kg * 5), combined the antioxidants
      and streptozotocin. The mice were sacrificed by cervical dislocation. In the
      experimental group given combined antioxidants following results were observed
      compared to diabetic group: increased percent insulin-positive cell area;
      decreased blood glucose levels; increased manganase superoxide dismutase
      activities and unsignificantly increased superoxide dismutase activities;
      unsignificantly decreased lipid peroxidase levels in both of fraction;
      unsignificantly decreased in mitochondrial fraction and unsignificantly increased
      in cytosolic fraction for catalase levels; not any alteration glutathione levels;
      not any activity in both of fraction for glutathione peroxidase. We can say that
      by taking the blood glucose levels and immunohistochemical results into account,
      the combination of triple antioxidants has a partly positive effect on diabetes.
      This positive effect could increase when trying different doses of combined
      antioxidant treatment.

PMID- 21968282
TI  - Co-existing neuroma of the palmar cutaneous branch of the median nerve and an
      arterio-venous malformation after open carpal tunnel decompression.

PMID- 21968283
TI  - Mupirocin resistance is not an inevitable consequence of mupirocin use.
AB  - The rate of mupirocin resistance in meticillin-resistant Staphylococcus aureus
      (MRSA) in Besancon University Hospital is low with a decreasing trend, from 10%
      in 2004 to 3% in 2009. This trend in resistance paralleled mupirocin consumption.
      Genotyping results showed that this decrease was not linked to a change in MRSA
      clones. It appears that the way in which the mupirocin is used, rather than the
      volume, plays a role in the emergence of resistance and that its cautious use is
      likely to maintain the mupirocin resistance at a low level, thus preserving its
      efficacy.

PMID- 21968285
TI  - Risk of continued institutionalization after hospitalization in older adults.
AB  - BACKGROUND: Little is known about the role of hospitalization as a risk factor
      for placement into long-term care. We therefore sought to estimate the percentage
      of long-term care nursing home stays precipitated by a hospitalization and
      factors associated with risk of nursing home placement after hospitalization.
      METHODS: We studied a retrospective cohort of a 5% sample of Medicare enrollees
      aged >= 66 years. The study included 762,243 patients admitted 1,149,568 times in
      January-April of 1996-2008, with 3,880,292 nonhospitalized controls. We measured
      residence in a nursing home 6 months after hospitalization. RESULTS: From 1996
      through 2008, 5.55% of hospitalized patients resided in a nursing home 6 months
      later compared with 0.54% of nonhospitalized control patients. Three quarters of
      new nursing home placements were precipitated by a hospitalization. Independent
      risk factors for long-term care placement after hospitalization included advanced
      age (odds ratio [OR] = 3.56 for age 85-94 vs. 66-74 years), female gender (OR =
      1.41), dementia (OR = 6.15), and discharge from the hospital to a skilled nursing
      facility (SNF; OR = 10.83). Having a primary care physician was associated with
      reduced odds (OR = 0.75). In the adjusted analyses, risk of institutionalization
      after hospitalization decreased 4% per year from 1996 to 2008. There were very
      large geographic variations in rates of long-term care after hospitalization,
      from < 2% in some hospital referral regions to > 13% in others for patients > 75
      years in 2007-2008. CONCLUSIONS: Most placements in nursing homes are preceded by
      a hospitalization followed by discharge to a SNF. Discharge to a SNF is
      associated with a high risk of subsequent long-term care.

PMID- 21968286
TI  - The evolutionary history of TLR4 polymorphisms in Europe.
AB  - Infections exert important evolutionary pressures shaping the human genome,
      especially on genes involved in host defense. A crucial step for host defense is
      recognition of pathogens by pattern recognition receptors on innate immune cells,
      among which Toll-like receptor 4 (TLR4) is one of the best known. Genetic
      variation in TLR4 (Asp299Gly, Thr399Ile) has been recently described. Haplotype
      frequencies of these polymorphisms differ among African, Asian and European
      populations, suggesting evolutionary pressures exerted by local infections. The
      TLR4 299Gly/399Ile haplotype, characteristic mainly of European populations, has
      relatively high frequency in the Iberian peninsula. This region is also described
      as refuge area during the last glacial maximum 20,000 years ago, from which
      repopulation of Europe took place. We speculate that a genetic bottleneck in the
      Iberian peninsula could have promoted the increased frequency of this haplotype
      by genetic drift. This hypothesis is supported by three arguments: (1) the West
      East gradient of prevalence in the haplotype among European populations; (2)
      ancient DNA from Neolithic burials in the Iberian peninsula, dated 6,600-4,500
      years before present, confirmed the relatively high frequency of this haplotype
      in the region, and (3) no functional differences between this haplotype and wild
      type TLR4 have been found. In contrast, the disappearance of the 299Gly/399Thr
      haplotype in Europe is most likely due to negative selection due to sepsis. In
      conclusion, differences in distribution of TLR4 polymorphisms Asp299Gly and
      Thr399Ile in European populations are most likely due to a combination of
      population migration events combined with selection due to sepsis.

PMID- 21968287
TI  - Efficiency of host utilisation by coleopteran parasitoid.
AB  - In insect larvae, optimising food utilisation with respect to available meals and
      time is essential for achieving maximum adult body size, which is a relevant
      proxy of fitness. We studied the efficiency of food conversion, body size,
      mortality, and development time in a solitary idiobiont ectoparasitoid, Brachinus
      explodens (Coleoptera: Carabidae), reared in the laboratory on the pupae of
      another carabid genus, Amara. The efficiency of conversion index (ECI - ratio of
      ingested to assimilated food) was, on average, 54.1+/-1.1% (n=76), with a minimum
      of 26.9% and a maximum of 81.6%. The rate of increase in biomass gained
      (W(gained)) with biomass of the host was constant in females, but it decreased in
      males over the range of host body mass. Females, therefore, grew heavier from
      hosts of the same mass compared to males. Body length increased with the host
      mass and was correlated with W(gained) identically for both sexes. Mortality was
      unaffected by the host mass, but it significantly increased below 20 degrees C.
      In contrast, the development time of the feeding phase of the larva increased
      with the host mass at 20.3 and 23.7 degrees C, but it remained unaffected at 26.9
      degrees C and in all three temperatures considering pupal development. W(gained)
      increased with development time up to ca. 8 days of larval feeding at 23.7
      degrees C. To our knowledge, our data are the first on food utilisation in
      solitary idiobiont coleopteran ectoparasitoids, and they present the highest
      values of ECI in insects.

PMID- 21968288
TI  - Heart failure, atrial fibrillation and neuromuscular disorders influence
      mortality in left ventricular hypertrabeculation/noncompaction.
AB  - OBJECTIVES: The prognosis of patients with left ventricular
      hypertrabeculation/noncompaction (LVHT) is controversial. The aim of the study
      was to assess parameters influencing mortality and to compare the mortality of
      LVHT patients with that of the general population of Austria. METHODS AND
      RESULTS: Included were patients with LVHT diagnosed echocardiographically between
      June 1995 and February 2011. They underwent a baseline cardiologic examination
      and were invited for neurological investigation. Between January and February
      2011, their survival status was assessed. LVHT was diagnosed in 162 patients (46
      females, aged 53 +/- 16 years) with a prevalence of 0.31%/year. One hundred and
      sixteen patients (72%) underwent a neurological investigation which revealed
      specific neuromuscular disorders (NMD) in 25 and NMD of unknown etiology in 74
      patients, and 17 subjects were assessed as normal. During the follow-up of 67
      months, mortality was 4.8%/year and the standardized mortality ratio was 6.27,
      compared with the Austrian population. By multivariate analysis, predictors of
      mortality were heart failure (hazard ratio 3.91, 4.48 and 5.37 for the New York
      Heart Association class II, III and IV, respectively), atrial fibrillation
      (hazard ratio 3.26) and NMD (hazard ratio 1.86). CONCLUSION: Prognostic
      predictors in LVHT are heart failure, atrial fibrillation and NMD. Whether
      optimal therapy of heart failure and atrial fibrillation will improve the
      prognosis of LVHT patients has to be addressed by further studies.

PMID- 21968289
TI  - Hydrogen sulfide is an oxygen sensor in the carotid body.
AB  - There is considerable controversy surrounding the initial step that transduces a
      fall in  [Formula: see text]  into a physiological signal, i.e., the "oxygen
      sensor" in chemoreceptors. Initial studies on systemic and respiratory vessels
      suggested that the metabolism of hydrogen sulfide (H(2)S) could serve as the
      oxygen sensor. This model was subsequently extended to chemoreceptors in fish and
      tissues of other animals. In this model, constitutive production of biologically
      active H(2)S is offset by H(2)S oxidation; when oxygen availability falls,
      production of H(2)S exceeds metabolism, and the resultant increase in
      intracellular H(2)S initiates the appropriate physiological responses. This model
      is supported by observations that the effects of hypoxia and H(2)S are similar,
      if not identical in many tissues: hypoxic responses are inhibited by inhibitors
      of H(2)S biosynthesis and augmented by sulfur donating molecules, and the tipping
      point between H(2)S production and oxidation occurs at physiologically relevant 
      [Formula: see text] . Recent studies from other laboratories support this
      mechanism of O(2) sensing in the carotid body. This review summarizes information
      that supports the H(2)S metabolic hypothesis in these tissues with emphasis on
      the carotid chemoreceptors. Evidence suggesting that H(2)S is not involved in
      oxygen sensing in the carotid body is also critically evaluated.

PMID- 21968290
TI  - Prognostic factors and outcomes in 28 cases of uterine leiomyosarcoma.
AB  - OBJECTIVES: It was the aim of this study to evaluate clinicopathological
      characteristics and prognostic factors of uterine leiomyosarcomas (LMS). METHODS:
      Twenty-eight patients with uterine LMS were evaluated in this retrospective
      study. Their features and survival were analyzed by Kaplan-Meier and log-rank
      tests. RESULTS: The median age of the patients was 52 years (range 25-74). Nine
      patients had a disease with a mitotic count <10/10 high-power fields. Twenty-one
      patients presented with stage I disease, 1 with stage II and 6 with stage IV.
      Twelve patients underwent total hysterectomy and bilateral salpingo-oophorectomy,
      2 simple hysterectomy, 5 myomectomy and 9 more comprehensive surgical treatments.
      Adjuvant chemotherapy was administered to 16 patients, whereas chemoradiation was
      given only to 2 patients. Fifty percent presented with recurrence of the disease.
      The median overall survival was 46 months. Age, mitotic count, type of surgery,
      adjuvant therapy, recurrence and clinical response to chemotherapy were not found
      to affect survival, while the menopausal status and FIGO (International
      Federation of Gynecology and Obstetrics) stage were found to be prognostic
      factors. CONCLUSION: In our series, the menopausal state and FIGO stage were
      found to be prognostic factors related to survival.

PMID- 21968291
TI  - Characterization of an Enterococcus faecium small-colony variant isolated from
      blood culture.
AB  - Small-colony variants (SCVs) of bacteria are slow-growing subpopulations which
      can cause latent or recurrent infections due to better intracellular survival
      compared to their wild-type counterparts. Atypical colony morphology and altered
      biochemical profile may lead to failure in identification of SCV strains. We here
      report for the first time the isolation of an Enterococcus faecium SCV phenotype.
      The case of a 65-year-old woman with acute myeloid leukaemia who developed
      symptoms of sepsis during induction chemotherapy is presented. E. faecium with
      normal and SCV phenotype was isolated from blood cultures. At the same time urine
      culture was positive with E. faecium suggesting that bacteraemia originated from
      the urinary tract. The SCV phenotype was characterized by atypical growth
      behaviour. Electron microscopic analyses revealed perturbation of the separation
      of daughter cells and the accumulation of cell wall material. Accordingly, the
      SCV variant showed a dysfunction or lack of spontaneous autolysis whereas the
      normal phenotype did not. In contrast to conventional identification systems
      based on biochemical characteristics, the E. faecium SCV was precisely identified
      by MALDI-TOF MS analysis implemented in our laboratory. Hence, the increasing use
      of MALDI-TOF MS analysis for the identification of bacteria might be an
      appropriate tool for the detection of SCV variants, the diagnosis of which is of
      importance for the clinical outcome and the antibiotic treatment.

PMID- 21968292
TI  - How funding structures for HIV/AIDS research shape outputs and utilization: a
      Swiss case study.
AB  - BACKGROUND: Research policy in the field of HIV has changed substantially in
      recent decades in Switzerland. Until 2004, social science research on HIV/AIDS
      was funded by specialized funding agencies. After 2004, funding of such research
      was "normalized" and integrated into the Swiss National Science Foundation as the
      main funding agency for scientific research in Switzerland. This paper offers a
      longitudinal analysis of the relationship between the changing nature of funding
      structures on the one hand and the production and communication of policy
      relevant scientific knowledge in the field of HIV on the other hand. METHODS: The
      analysis relies on an inventory of all social sciences research projects on HIV
      in Switzerland that were funded between 1987 and 2010, including topics covered
      and disciplines involved, as well as financial data. In addition, in-depth
      interviews were conducted with 18 stakeholders. RESULTS: The analysis highlights
      that the pre-2004 funding policy ensured good coverage of important social
      science research themes. Specific incentives and explicit promotion of social
      science research related to HIV gave rise to a multidisciplinary, integrative and
      health-oriented approach. The abolition of a specific funding policy in 2004 was
      paralleled by a drastic reduction in the number of social science research
      projects submitted for funding, and a decline of public money dedicated to such
      research. Although the public administration in charge of HIV policy still
      acknowledges the relevance of findings from social sciences for the development
      of prevention, treatment and care, HIV-related social science research does not
      flourish under current funding conditions. CONCLUSIONS: The Swiss experience
      sheds light on the difficulties of sustaining social science research and
      multidisciplinary approaches related to HIV without specialized funding agencies.
      Future funding policy might not necessarily require specialized agencies, but
      should better take into account research dynamics and motivations in the field of
      social sciences.

PMID- 21968293
TI  - Cofactors and metabolites as potential stabilizers of mitochondrial acyl-CoA
      dehydrogenases.
AB  - Protein misfolding is a hallmark of a number of metabolic diseases, in which
      fatty acid oxidation defects are included. The latter result from genetic
      deficiencies in transport proteins and enzymes of the mitochondrial beta
      oxidation, and milder disease conditions frequently result from conformational
      destabilization and decreased enzymatic function of the affected proteins. Small
      molecules which have the ability to raise the functional levels of the affected
      protein above a certain disease threshold are thus valuable tools for effective
      drug design. In this work we have investigated the effect of mitochondrial
      cofactors and metabolites as potential stabilizers in two beta-oxidation acyl-CoA
      dehydrogenases: short chain acyl-CoA dehydrogenase and the medium chain acyl-CoA
      dehydrogenase as well as glutaryl-CoA dehydrogenase, which is involved in lysine
      and tryptophan metabolism. We found that near physiological concentrations (low
      micromolar) of FAD resulted in a spectacular enhancement of the thermal
      stabilities of these enzymes and prevented enzymatic activity loss during a 1h
      incubation at 40 degrees C. A clear effect of the respective substrate, which was
      additive to that of the FAD effect, was also observed for short- and medium-chain
      acyl-CoA dehydrogenase but not for glutaryl-CoA dehydrogenase. In conclusion,
      riboflavin may be beneficial during feverish crises in patients with short- and
      medium-chain acyl-CoA dehydrogenase as well as in glutaryl-CoA dehydrogenase
      deficiencies, and treatment with substrate analogs to butyryl- and octanoyl-CoAs
      could theoretically enhance enzyme activity for some enzyme proteins with
      inherited folding difficulties.

PMID- 21968294
TI  - The comparison of equine articular cartilage progenitor cells and bone marrow
      derived stromal cells as potential cell sources for cartilage repair in the
      horse.
AB  - A chondrocyte progenitor population isolated from the surface zone of articular
      cartilage presents a promising cell source for cell-based cartilage repair. In
      this study, equine articular cartilage progenitor cells (ACPCs) and equine bone
      marrow-derived stromal cells (BMSCs) were compared as potential cell sources for
      repair. Clonally derived BMSCs and ACPCs demonstrated expression of the cell fate
      selector gene, Notch-1, and the putative stem cell markers STRO-1, CD90 and
      CD166. Chondrogenic induction revealed positive labelling for collagen type II
      and aggrecan. Collagen type X was not detected in ACPC pellets but was observed
      in all BMSC pellets. In addition, it was observed that BMSCs labelled for Runx2
      and matrilin-1 antibodies, whereas ACPC labelling was significantly less or
      absent. For both cell types, osteogenic induction revealed positive von Kossa
      staining in addition to positive labelling for osteocalcin. Adipogenic induction
      revealed a positive result via oil red O staining in both cell types. ACPCs and
      BMSCs have demonstrated functional equivalence in their multipotent
      differentiation capacity. Chondrogenic induction of BMSCs resulted in a
      hypertrophic cartilage (endochondral) phenotype, which can limit cartilage repair
      as the tissue can undergo mineralisation. ACPCs may therefore be considered
      superior to BMSCs in producing cartilage capable of functional repair.

PMID- 21968296
TI  - CPAP increases 6-minute walk distance after lung resection surgery.
AB  - BACKGROUND: The application of CPAP has been used to minimize postoperative
      pulmonary complications after lung resection surgery. The aim of this study was
      to quantify both the CPAP effects upon lung function and functional capacity in
      early postoperative lung resection, as well as  to evaluate if CPAP prolongs air
      leak through the chest drain. METHODS: Thirty patients in the postoperative
      period of lung resection were allocated into 2 groups: an experimental group,
      consisting of 15 patients who underwent a 10 cm H(2)O CPAP, and a 15 patient
      control group, who  performed breathing exercises. Arterial blood gas analysis,
      peak expiratory flow (PEF), respiratory muscle strength, spirometry, and 6-min
      walk test (6MWT) were assessed in the preoperative period, and repeated
      postoperatively on the first and on the seventh day (6MWT was repeated only on 
      the seventh day). RESULTS: Significant increases in PEF, muscle strength, and
      FEV(1) between the first and seventh postoperative day were observed, both in the
      experimental and in the control group, whereas FVC and P(aO(2)) increased
      significantly between the first  and seventh postoperative day only in the
      experimental group. The average loss in 6-min walk distance (6MWD) from
      preoperative to postoperative day 7 in the experimental group was significantly
      lower than in control group. When comparing the 2 groups, only 6MWD was
      statistically different  (P < .001). There was no air leakage increase through
      the drain with the early use of CPAP. CONCLUSION: When compared to breathing
      exercises, CPAP increases the 6MWD in postoperative lung resection patients,
      without prolonging air leak through the chest drain.

PMID- 21968297
TI  - Taming influenza viruses.
AB  - Plasmid-based reverse genetics systems allow the artificial generation of viruses
      with cloned cDNA-derived genomes. Since the establishment of such systems for
      influenza virus, numerous attempts have been made to tame this pathogenic agent.
      In particular, several types of viruses expressing foreign genes have been
      generated and used to further our knowledge of influenza virus replication and
      pathogenicity and to develop novel influenza vaccines. Here, we review these
      achievements and discuss future perspectives.

PMID- 21968299
TI  - Borna disease virus - fact and fantasy.
AB  - The occasion of Brian Mahy's retirement as editor of Virus Research provides an
      opportunity to reflect on the work that led one of the authors (Lipkin) to meet
      him shortly after the molecular discovery and characterization of Borna disease
      virus in the late 1980s, and work with authors Briese and Hornig to investigate
      mechanisms of pathogenesis and its potential role in human disease. This article
      reviews the history, molecular biology, epidemiology, and pathobiology of
      bornaviruses.

PMID- 21968300
TI  - [Construction and identification of adenoviral vectors expressing shRNA targeting
      CDK1 gene].
AB  - AIM: To construct three adenoviral vectors harboring shRNA targeting CDK1 gene,
      and identify its inhibitory effect on the gene expression of CDK1 in hepatoma
      carcinoma HepG2 cells. METHODS: Three shRNA sequences targeting CDK1 mRNA were
      designed. The shRNA sequences were annealed and linked with linearized pSIREN
      RetroQ-ZsGreen. The recombinants were identified by PCR and DNA sequencing. CDK1
      shRNA plasmid was then transfected into the cultured HepG2 cell line with
      lipofectamine 2000. RT-PCR and Western blot were used to detect the mRNA and
      protein expression of CDK1,  respectively. RESULTS: The small hair-pin RNA
      sequences were successfully inserted into pSIREN-RetroQ-ZsGreen vector,  and the
      sequences were identified by DNA sequencing. Further,  Realtime PCR and Western
      blot results validated that the three small hair-pin RNAs effectively knockdowned
      the expression of endogenous CDK1 in HepG2 cells. CONCLUSION: CDK1-shRNA can be
      effectively transfected into HepG2 cells,  and induce post-transcriptional gene
      silencing of CDK1,  which enables further functional study on CDK1.

PMID- 21968298
TI  - Novel vaccines against influenza viruses.
AB  - Killed and live attenuated influenza virus vaccines are effective in preventing
      and curbing the spread of influenza epidemics when the strains present in the
      vaccines are closely matched with the predicted epidemic strains. These vaccines
      are primarily targeted to induce immunity to the variable major target antigen,
      hemagglutinin (HA) of influenza virus. However, current vaccines are not
      effective in preventing the emergence of new pandemic or highly virulent viruses.
      New approaches are being investigated to develop universal influenza virus
      vaccines as well as to apply more effective vaccine delivery methods. Conserved
      vaccine targets including the influenza M2 ion channel protein and HA stalk
      domains are being developed using recombinant technologies to improve the level
      of cross protection. In addition, recent studies provide evidence that vaccine
      supplements can provide avenues to further improve current vaccies.

PMID- 21968301
TI  - [Significance of the expression of lymphocytes and cytokines infiltrating in
      HCC].
AB  - AIM: To reveal the classification of lymphocytes and expression of cytokines
      infiltrating in HCC,  and investigate the significance of changes of immune
      microenvironment in HCC. METHODS: 76 tumor and non-tumor tissues of HCC were
      collected to detect the amount of immune cells in the tissues by FCM and
      immunohistochemistry (IHC). Th1/Th2 cytokines in tissues were detected by
      Cytometric bead array (CBA),  and TGF-1,  VEGF detected by ELISA. RESULTS: There
      were more CD3(+); T cells,  CD4(+); Th cells,  Treg cells,  and CD45RO(+); memory
      T cells in tumors than in non-tumor tissues. On the contrary there were less
      CD8(+); CTLs in tumors. There was negative correlation between Treg and Th or CTL
      cells. CD69,  which is the early activating factor,  expressed less on CD3(+); T
      cells and NK cells in tumors than non-tumor tissues. Whereas HLA-DR,  which is
      the late activating factor,  expressed more on CD3(+); T cells in tumors than non
      tumor tissues. More IL-10,  TGF-1 and VEGF were secreted in tumors than non-tumor
      tissues. CONCLUSION: Along with the decrease of effective immune cells and
      increase of suppressor immune cells and cytokines,  the lymphocytes infiltrating
      in the tumor were immune incompitence,  which contributed to the tumorigenesis.

PMID- 21968302
TI  - [The influence of tripterygium hypoglaucum hutch on the HIF-1alpha  expression in
      the CIA rat models].
AB  - AIM: To investigate the effect of tripterygium hypoglaucum hutch (THH) on the
      expression of hypoxi induciable factor (HIF-1alpha) in rats with collagen induced
      arthritis (CIA) model and its mechanism. METHODS: Establish CIA model rat,  group
      randomly,  treat groups with gastric feeding at High,  Medium and Low doses of
      THH once a day,  with continuous medication for 30 days. Record arthritis index
      (AI) and joint pathology change. Detect HIF-1alpha mRNA and protein expression
      with PT-PCR and immunohistochemical staining. RESULTS: THH could inhibit paw
      swelling in CIA rats,  reduce synovial proliferation and inflammatory response
      significantly. CONCLUSION: THH may mitigate joint inflammation of CIA model rat
      through reduction of HIF-1alpha expression.

PMID- 21968303
TI  - [Expression and significance of IL-10 in human chorionic villi of recurrent
      spontaneous abortion].
AB  - AIM: To investigate the correlation between interleukin-10(IL-10) and recurrent
      spontaneous abortion as well as the significance of them through researching the
      comparison of histological localization of IL-10,  expression comparison of IL-10
      mRNA in human chorionic villi of pregnant women with recurrent spontaneous
      abortion and normal abortion. METHODS: To detect expression comparison of IL-10
      mRNA and histological localization of IL-10 in human chorionic villi of 35
      pregnant women with recurrent spontaneous abortion(experimental group) and 35
      normal abortion women(control group) by reverse transcription-polymerase chain
      reaction and immunohistochemistry. To analysis expression of IL-10 in serum of
      the two groups by ELISA. RESULTS: The detection of immunohistochemistry showed
      that there are expressions of IL-10 both in the two groups,  the expressions of
      IL-10 in the experimental group were lower than the control group(P<0.05).The
      results of the RT-PCR showed that the expressions of IL-10 of experimental group
      were lower than the control group(P<0.05). ELISA analysis showed that the
      expressions of IL-10 of the experimental group were lower than the control
      group(P<0.05). CONCLUSION: The results of detection of immunohistochemistry and
      the expression of mRNA of IL-10 in human chorionic villi as well as its
      expressions in serum of experimental group were lower than the control group. IL
      10 would play an important role in maintaining normal pregnancy.

PMID- 21968305
TI  - [Construction of eukaryotic expression vector encoding ACRBP and its expression
      in hepatocarcinoma cells].
AB  - AIM: To construct the eukaryotic expression vector pEGFP-N1/ACRBP and stably
      express ACRBP in human hepatocarcinoma cells,  providing functional clues for
      ACRBP. METHODS: A recombinant plasmid pMAL-C2/ACRBP was used as a template to
      amplify ACRBP cDNA. The PCR product was ligated into an eukaryotic expression
      vector pEGFP-N1 to construct a recombinant plasmid pEGFP-N1/ACRBP. Then the pEGFP
      N1/ACRBP was transfected by Fugene HD into ACRBP-negative HepG2 cells. The stably
      transfected clones were selected by G418. RT-PCR and immunohistochemistry were
      used to detect the expression of ACRBP in HepG2 cells. RESULTS: The eukaryotic
      expression vector pEGFP-N1/ACRBP was constructed and confirmed by sequencing. The
      stably transfected HepG2 cells expressed ACRBP. CONCLUSION: The eukaryotic
      expression vector pEGFP-N1/ACRBP has been successfully constructed and
      transfected into HepG2 cells,  resulting in stable expression of ACRBP.

PMID- 21968304
TI  - [The expression and significance of Notch1 in the human kidney tubular cell
      transdifferentiation induced by TGF-beta(1);].
AB  - AIM: To explore the dynamic expression and significance of Notch1 in the human
      kidney tubular epithelial cell transdifferentiation (KTECT)induced by TGF
      beta(1);. METHODS: Normal human kidney epithelial cell line (HK-2) was cultured
      and then divided into blank group,  and TGF-beta(1);(10 ng/mL) induced group. At
      the 12 h,  24 h, 48 h and 72 h, the morphologic changes of HK-2 cells were
      observed under an inverted phase contrast microscope. The expression of alpha
      SMA, E-cadherin and Notchl as well as their mRNA were examined by immunohisto
      chemistry staining and RT-PCR respictively. RESULTS: Compared with the  normal
      control group,  the expression levels ofalpha-SMA and Notchl markedly increased
      in TGF-beta(1); induced group (P<0.05), but the expression of E-cadherin
      obviously reduced(P<0.05). The expression of Notch1 protein and its mRNA was
      positively correlated to the expression ofalpha-SMA(r(protein);=0.958;
      r(mRNA);=0.944; P<0.05), and was negatively correlated to the expression of E
      cadherin(r(protein);=-0.937; r(mRNA);=-0.921; P<0.05). CONCLUSION: Notch1 may
      participate in the KTECT induced by TGF-beta(1);.

PMID- 21968306
TI  - [Cloning and expression of a outer membrance protein gene(OmpS(2);) of
      Edwardsiella tarda HB01 and its immunogenicity].
AB  - AIM: To construct a recombinant strain BL21(DE3)(pET-28a-OmpS(2);),  and obtain a
      genetic engineering vaccine to provide protective immunity against diseases
      caused by Edwardsiella tarda. METHODS: According to the GenBank sequences
      (GenBank Accession No. AY078509), one pair of primers was designed and the outer
      membrance protein gene (OmpS(2);) of Edwardsiella tarda HB01 was amplified by
      PCR.  The OmpS(2); gene was cloned in pET-28a vector and transformed into
      Escherichia coli BL21(DE3). The OmpS(2); protein was highly expressed when the
      recombinant strain BL21 (DE3) (pET-28a-OmpS(2);) was induced by IPTG. The
      expressed protein was 47 kD as estimated by 150 g/L SDS-polyacrylamide gel
      electrophoresis (SDS-PAGE). RESULTS: The immunogenicity of the expressed OmpS(2);
      protein was confirmed by Western blotting. Mice and Paralichthys olivaceus were
      immunized with the genetic engineering vaccines of Edwardsiella tarda and
      Aeromonas hydrophila,  showing promise that all these vaccines have a high
      protective ability.  And the protective ability to Edwardsiella tarda and
      Aeromonas hydrophila in Paralichthys olivaceus respectively reached  70% and 80%.
      CONCLUSION: The recombinant strain BL21 (DE3)(pET-28a-OmpS(2);) could be
      candidate of genetic engineering vaccine to provide protective immunity against
      diseases caused by Edwardsiella tarda.

PMID- 21968307
TI  - [Prokaryotic expression, purification and antigenicity identification of human
      GRP78 protein].
AB  - AIM: To construct a recombinant plasmid pGEX-4T-1-GRP78,  express it and purify
      human glucose regulated protein 78 (GRP78). METHODS: GRP78 gene was amplified by
      PCR from the recombinant vector constructed in our laboratory. The PCR product
      was inserted into pGEX-4T-1 prokaryotic expression vector to generate pGEX-4T-1
      GRP78. The pGEX-4T-1-GRP78 was then transformed into BL21 and GRP78 was expressed
      on induction of IPTG. After purification,  GRP78 was released by thrombin
      cleavage,  and its antigenicity was identified by ELISA. RESULTS: The GRP78
      prokaryotic expression vector was successfully constructed as confirmed by enzyme
      digestion and DNA sequencing. ELISA demonstrated the antigenicity of the purified
      GRP78 protein. CONCLUSION: The recombinant prokaryotic expression vector pGEX-4T
      1-GRP78 has been constructed successfully. The purified GRP78 has been obtained
      with good antigenicity,  which will be used for GRP78-based serum diagnosis of
      hepatocellular carcinoma.

PMID- 21968308
TI  - [TLR9 expression and its relationship with MCP-1 and TNF-alpha in HCV-stimulated
      BV2 cells].
AB  - AIM: To detect TLR9 expression and its effect on the secretion of MCP-1 and TNF
      alpha after mouse microglia (BV2) were infected by hepatitis C virus (HCV),  and
      to explore the mechanism of HCV-induced central nervous system (CNS) infection.
      METHODS: BV2 cells were cultured in vitro and divided into a HCV-positive serum
      group,  a normal serum group (negative control) and a blank control group,  with
      each group of 20 samples. The cells and the supernatants were collected at 12 h, 
      detected for TLR9 expression by flow cytometry (FCM),  and determined for the
      levels of TNF-alpha and MCP-1 by ELISA. Then the data was statistically analyzed
      by SPSS11.0. RESULTS: (1) FCM showed TLR9 expression in all three groups,  with
      the strongest expression in the HCV-positive serum group (P<0.01),  while there
      was no statistical significance between the normal serum group and the blank
      control group (P>0.05). (2) The levels of TNF-alpha and MCP-1 in the HCV-positive
      serum group were higher than those in the other groups (P<0.01),  which
      correlated with enhanced TLR9 expression in the HCV-positive serum group.
      CONCLUSION: HCV-positive serum causes enhanced TLR9 expression and the secretion
      of MCP-1 and TNF-alpha. in BV2 cells,  suggesting the involvement of TLR9 in the
      early inherent immune response triggered by HCV-induced CNS infection.

PMID- 21968309
TI  - [The effects of inoculation route and adjuvant type on the immunizing potency of
      CVB3 VP1 protein].
AB  - AIM: To explore the effects of inoculation route and adjuvant type on the
      immunizing potency of  coxsackievrus B type 3 (CVB3) VP1 protein. METHODS: The
      recombinant plasmid pET-His/VP1 expressed CVB3 VP1 was transformed into E.coli
      BL21(DE3) pLysS and induced to express VP1 protein by IPTG,  and verified by
      Western blot analysis. The fusion VP1 protein was purified with Ni affinity
      chromatography. Firstly, BALB/c mice were administered via different inoculation
      route(subcutaneous,  intraperitoneal,  intramuscular), with twelves mice in each
      group. Secondly,  combined with various adjuvants (Alum,  Freund's adjuvant, 
      Montanide ISA720), with eighteen mice in each group. The mice were immunized
      three times at a three week interval with 50 MUg of VP1 protein. The titers of
      sera IgG and neutralizing antibody were detected by ELISA and neutralization
      assay. Cell mediated immune response was tested by the lymphocytes proliferation
      activity and specific CTL cytotoxic activity. The mice were challenged with
      lethal dose of CVB3,  the titers of the sera virus were titrated. Furthermore, 
      the survival rates of mice were observed. RESULTS: The VP1 protein was expressed
      in E.coli successfully and the fusion protein was purified. In different
      inoculation route, the titers of neutralizing antibody and specific IgG in
      intramuscular injection group was much higer than other groups (P<0.01). VP1
      protein in combination with Montanide ISA720 and Freund's adjuvant elicit higher
      titer antibodies and cell mediated immune response,  and the virus titers in
      blood were lower in comparison to Alum adjuvant group (P<0.05).The survival rate
      of Freund' adjuvant group was better than adjuvant AL(OH)(3); group (P<0.05).
      CONCLUSION: The VP1 protein combined with ISA720 and Freund's adjuvant given by
      intramuscular injection may induce an improved immune responses and the better
      survival rates of the mice after virus challenge.

PMID- 21968310
TI  - [Establishment of bacteria display technology for Fab antibody library
      screening].
AB  - AIM: To establish bacterial display technology for the purpose of Fab antibody
      library screening,  by using six amino acids (CDQSSS) of the amino termimus of
      NlpA protein to anchore antibodies to the periplasmic side of the bacterial inner
      membrane. METHODS: The NlpA Leader sequences (encoding CDQSSS) was amplified from
      pNAD plasmid. The PCR product was subcloned into pComb3 expression vector to
      generate Fab display vector pBFD. The heavy chains of the Fab gene fragments and
      the light chains of the anti-human IL-1beta (hIL-1beta) antibody were inserted
      downstream of the NlpA leader and pelB leader respectively to construct the pBFD
      Fab for Fab antibody display. Then pBFD-Fab transformed E.coli DH5alpha was
      induced by IPTG to express the Fab antibodies,  as detected by flow cytometry
      (FCM),  and positive populations were sorted. Instead of PCR,  plasmids were
      extracted for rescue purpose. The rescue plasmids were retransformed to E.coli
      DH5alpha and FCM was performed again. RESULTS: The pBFD-Fab-transformed bacteria
      were incubated with antigen and antigen specific FITC-antibody,  and showed
      strong fluorescence as detected by FCM in a dose-dependent manner. The rescued
      pBFD-Fab displayed similar fluorescence intensity,  indicating the reliability of
      this technology. CONCLUSION: The Fab expressed by the bacterial display system
      folds efficiently and binds to hIL-1beta specifically. The plasmid rescue works
      well and it can avoid mutation and mis-pairing chains. This bacterial display
      technology has the stability of antibody expression. This study has used the
      technology to screen anti-hIL-1beta Fab antibody Library successfully.

PMID- 21968311
TI  - [Preparation and characterization of monoclonal antibody against HCCR protein].
AB  - AIM: Preparation of monoclonal antibody (mAb) to HCCR,  which is a candidate
      biomarker for human hepatocellular carcinoma (HCC). METHODS: The recombinant
      protein HCCR-1(167-360); was expressed and was used as immunogen to immunize
      mouse for generation of mAb against HCCR. The protein Ep-HCCR,  which displayed a
      epitope of HCCR,  was  also expressed and purified to use to detect serum
      antibody titer and to screen the positive clones of hybridmas. The properties of
      HCCR antibody were analyzed by ELISA,  Western blot,  immunofluorescence and
      immunohistochemistry. RESULTS: A hybridmas clone,  which secreted anti-HCCR mAb, 
      was obtained. The affinity constant (Kaff) of the mAb is 5.4*10(6); L/mol
      analyzed by ELISA;  Western blot showed that the mAb could specifically recognize
      HCCR-1 and HCCR-2 expressed in HepG2 cells;  The mAb was also used to detect the
      expression of HCCR proteins in hepatoma cells and HCC tissues. The results of
      immunofluorescence indicated that HCCR proteins mainly localized on the plasma
      membrane and cytoplasm of HepG2 cells. In addition,  HCCR was found high
      expressed in HCC tissues but not in normal liver tissue detected by
      Immunohistochemistry. CONCLUSION: A specific mAb against HCCR was successfully
      generated,  which laid the foundation for establishing HCC detection method based
      on HCCR.

PMID- 21968312
TI  - [Monoclonal antibody preparation and identification of vascular endothelial
      growth factor 165 expressed in vitro].
AB  - AIM: To prepare a monoclonal antibody against human vascular endothelial growth
      factor (VEGF165),  for further study the VEGF165 in the tumorigenesis,  tumor
      cell migration and the tumor cells escape from the immune response. METHODS:
      VEGF165 gene was cloned from the human umbilical vein endothelial cells (HUVEC)
      by RT-PCR,  and then cloned into the pGEX-6P1,  constructed the prokaryotic
      expression of pGEX-6P1-VEGF165. The fusion -protein of VEGF165 was expressed in
      E.coli (BL21) induced by the 1.0 mmol/L IPTG at  37DegreesCelsius after 4 h. The
      fusion-protein was purified by the MicroSpin GST purification kit for immunized
      the BALB/c mouse. The monoclonal antibodies (mAbs) against the VEGF165 were
      prepared by hybridoma technique, and ELISA and Western blot identified their
      immunoglobulin subclass and specificity. And we used the inhibition the embryo
      angiogenesis assay,  inhibition the HUVEC migration assay and inhibition the
      HUVEC tubule information assay to study the bioactivity of the mAbs of VEGF165.
      RESULTS: The sequence of the VEGF165 is agreed to the GenBank,  and we obtained
      five species VEGF165 mAbs,  and the titer of the antibody is high,  and we named,
      they are 5A6, 3F5, 6H3, 7D10 and 7A10. Our study showed that the 5A6, 3F5, 6H3,
      7D10 were classified to IgG2a,  7A10 was classified to IgG2b,  and the light
      chain is k.Meanwhile the purified mAbs inhibited formation of chicken embryo
      blood vessels,  and inhibited tubule formation of the HUVEC and inhibited
      migration of the HUVEC. CONCLUSION: mAbs against human VEGF165 have the effective
      bioactivity,  which would play a significant role for further study the mechanism
      of VEGF165.

PMID- 21968313
TI  - [The preparation of rabbit antiserum against gekko japonicus Hoxc10  and it's
      property identification].
AB  - AIM: Prepare the rabbit antiserum against gecko japonicus Hoxc10 and to identify
      its properties. METHODS: Prokaryotic expression vector of g-Hoxc10 were
      constructed and then transform into E.coli (BL21). To make GST-g-Hoxc10 fusion
      protein in E.coli (BL21) under the optimized induction of Isopropyl beta-D-1
      thiogalactopyranoside(IPTG). The recombination proteins were purified using
      affinity chromatography. The purified fusion protein was inoculated into adult
      rabbits to develop antiserum. Western blot and immunohistochemistry staining were
      then performed to evaluate the feature of the prepared antiserum. RESULTS:
      Prokaryotic expression vectors of g-Hoxc10 were successfully constructed. The
      soluble recombinant protein was highly expressed in E.coli BL21 and inoculated
      into adult rabbits to obtain high titer antiserum. Western blot and
      immunohistochemistry staining were then performed to evaluate the specificity of
      the prepared antiserum. CONCLUSION: We successfully amplified and expressed the g
      Hoxc10 in E.coli BL21. The purified fusion protein was inoculated into adult
      rabbits to develop antiserum. The obtained antiserum of g-Hoxc10 showed a high
      titer against Hoxc10 proteins. The protein and antiserum prepared in this study
      can be used for further research of the function investigation of Hoxc10.

PMID- 21968314
TI  - [Expression of aldolase of Toxoplasma gondii and preparation of the polyclonal
      antibodies against this protein].
AB  - AIM: To produce the aldolase protein and its polyclonal antibody. METHODS:
      Aldolase gene was obtained from cDNA library by PCR amplification and subcloned
      to vector pET30a. The recombinant protein aldolase-His(6); was expressed in
      E.coli upon IPTG induction and then purified with affinity chromatography. The
      purified protein mixed with adjuvant was used to immunize SD rats to produce the
      polyclonal antibodies. RESULTS: The recombinant plasmid aldolase/pET30a was
      constructed successfully and expressed as a fusion protein aldolase-His(6);; 
      Polyclonal antibody against aldolase-His(6); was obtained from rat,  and antibody
      titer was 1:4 000. CONCLUSION: The purified protein aldolase-His(6); and its
      polyclonal antibodies were obtained,  which may provide the foundation for the
      further studies on the function of aldolase.

PMID- 21968315
TI  - [Prokaryotic expression and antibody preparation of human  GALNT3-sol protein].
AB  - AIM: In order to detect the expression of GALNT3 in various tumor tissues,  the
      prokaryotic expression vector of human GALNT3-sol (a truncation of GALNT3 being
      deleted of the hydrophobic trans-membrane domain) was constructed,  and then the
      recombinant GALNT3-sol protein was expressed and purified from E.coli,  followed
      by the preparation of polyclonal antibody against GALNT3-sol and characterization
      of its properties. METHODS: The human cDNA of GALNT3-sol (1 755 bp)was amplified
      from MKN45 cell line and cloned into expression vector pET5b/GALNT3-sol,  then
      transformed into E.coli BL21(DE3),  in which the GALNT3-sol protein was induced
      by IPTG and then purified by Electrophoresis.Mice were immunized with the
      purified protein and the anti-serum was collected at different time
      intervals.Properties of the anti-serum were further detected by ELISA and Western
      blot. RESULTS: The prokaryotic expression vector of pET15b/GALNT3-sol was
      constructed successfully.Human GALNT3-sol protein was expressed in E.coli  after
      IPTG induction.The titer of the obtained anti-serum reached 1:25 600,  and its
      specificity was proved by Western blot. CONCLUSION: Human GALNT3-sol protein can
      be successfully expressed in E.coli,  and the specific anti-human GALNT3-sol
      antibody can be obtained by immunization of mice,  which makes it possible to
      further investigate the role of GALNT3 in the progression of various tumors.

PMID- 21968316
TI  - A pilot study of endothelial dysfunction and aortic stiffness after interleukin-6
      receptor inhibition in rheumatoid arthritis.
AB  - Interleukin (IL)-6 is a pleiotropic proinflammatory cytokine involved in the
      pathogenesis of both atherosclerosis and rheumatoid arthritis. The role of the IL
      6/IL-6 receptor pathway in the documented acceleration of atherosclerosis in
      rheumatoid arthritis has not been examined. In a non-randomized prospective pilot
      study we asked whether endothelial dysfunction, defined as impaired flow mediated
      dilatation (FMD), and aortic stiffness, assessed by pulse wave velocity (PWV)
      improve after 3 and 6 monthly therapeutic infusions of the anti-IL-6 receptor
      antibody tocilizumab for active rheumatoid arthritis. We found that FMD increased
      from 3.3 +/- 0.8 to 4.4 +/- 1.2 to 5.2 +/- 1.9% (p = 0.003), whereas PWV
      decreased from 8.2 +/- 1.2 to 7.7 +/- 1.3 to 7.0 +/- 1.0m/s (p < 0.001). Whether
      these beneficial arterial changes are direct effects of the IL-6/IL-6 receptor
      pathway inhibition, maintained over time and translate into better clinical
      outcome warrants further studies.

PMID- 21968317
TI  - Imaging of the carotid artery.
AB  - In the study of carotid arteries, modern techniques of imaging allow to analyze
      various alterations beyond simple luminal narrowing, including the morphology of
      atherosclerotic plaques, the arterial wall and the surrounding structures. By
      using CTA and MRI it is possible to obtain three-dimensional rendering of
      anatomic structures with excellent detail for treatment planning. This paper will
      detail the role of various imaging methods for the assessment of carotid artery
      pathology with emphasis on the detection, analysis and characterization of
      carotid atherosclerosis.

PMID- 21968318
TI  - Plasma aldosterone levels and aldosterone-to-renin ratios are associated with
      endothelial dysfunction in young to middle-aged subjects.
AB  - OBJECTIVE: Small clinical studies suggested a role for aldosterone in the
      development of endothelial dysfunction. We investigated whether the plasma
      aldosterone concentration (PAC) or the aldosterone-to-renin ratio (ARR) were
      associated with decreased endothelial function as measured by flow-mediated
      dilation (FMD) of the brachial artery in the general population. METHODS: Our
      study population comprised 972 participants from the Study of Health in
      Pomerania, who were not treated with antihypertensive medication. We performed
      age-stratified (<50 and >= 50 years) ordinal logistic regression analyses. FMD
      was categorised as decreased (1st quintile), moderate (2nd-4th quintile), or
      increased (5th quintile). PAC and ARR were divided into low, moderate, and high
      values according to age- and sex-specific tertiles. All models were re-calculated
      for 871 subjects with PAC and ARR within the study-specific reference ranges.
      Odds ratios (OR) and 95% confidence intervals (CI) are presented. RESULTS:
      Subjects <50 years with high PAC (OR 1.60; 95% CI 1.07-2.38) or ARR (OR 1.81; 95%
      CI 1.21-2.73) had higher odds for decreased FMD than subjects with low PAC or
      ARR, respectively. Similar results were obtained in analyses restricted to
      subjects with PAC and ARR within the reference range. High-normal PAC (OR 1.62;
      95% CI 1.07-2.47) or ARR (OR 1.62; 95% CI 1.05-2.50) was associated with higher
      odds for decreased FMD when compared with low-normal PAC or ARR, respectively.
      These associations were not observed in subjects >= 50 years. CONCLUSIONS: High
      and high-normal PAC or ARR contribute to an impaired FMD and subsequently the
      progression of subclinical atherosclerosis in young to middle-aged subjects.

PMID- 21968319
TI  - Record-based, stepwise screening for type 2 diabetes integrated into an annual
      cardiovascular care review system: Findings from a UK general practice.
AB  - AIMS: Screening high-risk individuals for type 2 diabetes (T2DM) is recommended
      by many organisations. We report results from a pragmatic stepwise T2DM screening
      programme integrated into an annual review system in a UK general practice.
      METHODS: Patients with hypertension, cardiovascular disease or chronic kidney
      disease attending an annual review were screened for dysglycaemia by random blood
      glucose (RBG) measurement. At the discretion of the usual doctor, individuals
      with an RBG>=6.1 mmol/l were invited to return for fasting blood glucose (FBG) or
      HbA(1C) measurement, allowing diagnosis of T2DM. RESULTS: 786 eligible patients
      were invited for T2DM screening as part of their annual review. 544 attended
      screening, of whom 120 had an RBG>=6.1 mmol/l. 40 individuals attended FBG
      measurement and 8 individuals attended HbA(1C) measurement, leading to 9 T2DM
      diagnoses. The positive predictive value of the test for T2DM was 19% and the
      laboratory cost was L91 per patient diagnosed with T2DM. CONCLUSIONS: It is
      feasible to integrate a simple T2DM screening programme within an annual review
      system in a UK general practice. Different strategies may be required to increase
      initial attendance and ensure completion of the screening programme.

PMID- 21968320
TI  - What can topology changes in the oddball N2 reveal about underlying processes?
AB  - A prominent theory of the N2 event-related potential component holds that the
      'oddball' N2 is generated in the anterior cingulate cortex. However, observations
      of oddball N2s with posterior scalp distributions are inconsistent with this
      hypothesis. We suggest that variability in the topology of the oddball N2 is a
      key characteristic of the component that can inform theories of its neural basis.
      We propose that the oddball N2 reflects cortex-wide noradrenergic modulation of
      the ongoing cortical activity and thus should have a topology that varies
      systematically according to task specifics. Participants engaged in an oddball
      task with male and female faces tinted either yellow or blue, counting targets
      according to color or sex. Between blocks, targets were frequent or infrequent,
      counterbalanced across task (attend color, attend sex), and category (blue male,
      yellow male, blue female, yellow female). We created difference waves by
      subtracting frequent from infrequent category trials to isolate the oddball N2.
      When participants attended to color the oddball N2 was maximal over frontal
      central areas and when they attended to sex it was maximal over lateral-occipital
      areas. Thus, the oddball N2 has a variable scalp distribution that depends on the
      relative engagement of cortical areas, consistent with noradrenergic modulation
      having the greatest impact in those areas mostly engaged by the task at hand.

PMID- 21968321
TI  - Listening to factually incorrect sentences activates classical language areas and
      thalamus.
AB  - Neurophysiological underpinnings of the integration of information during
      sentence comprehension have been studied since 1980. However, little is known
      about integrative processes in sentences containing a word that is semantically
      congruent, but factually incompatible with the context. In this study, we aimed
      at investigating the differences between the brain regions involved in responses
      to factually correct and incorrect sentences. Eighteen healthy volunteers
      underwent functional MRI while listening passively to 40 correct and 40 incorrect
      sentences. The contrast between factually correct and incorrect sentence endings
      revealed large activation areas in the left inferior frontal gyrus, the left
      middle/superior temporal gyrus, and smaller activations of these areas' homologs
      in the right hemisphere, in the thalamus, and Brodmann area 6.

PMID- 21968322
TI  - Do not look there:  the impact of facial expression on location negative priming.
AB  - This study used the location negative priming (NP) paradigm and the recording of
      event-related potentials to examine the mechanism of the impact of emotional
      stimulus on subsequent spatial attentional processing. The results shown to be
      relative to the happy and neutral condition, a significant behavioural NP effect,
      as well as decreased N2, increased N2pc, and P3 amplitudes for NP condition, were
      found selectively in the fearful prime distractor condition. These findings
      suggest that the effect of fearful stimulus on location NP may be related to
      early-inhibition processing. Larger P3 amplitudes may reflect the use of
      increased cognitive resources when one is necessary for overcoming the tendency
      to avoid viewing the position where a fearful stimulus has recently been seen.

PMID- 21968323
TI  - Word repetition priming-induced oscillations in auditory cortex:  a
      magnetoencephalography study.
AB  - Magnetoencephalography was used in a passive repetition priming paradigm. Words
      in two frequency bins (high/low) were presented to the participants auditorily.
      Participants' brain responses to these stimuli were analyzed using synthetic
      aperture magnetometry. The main finding of this study is that single-word
      repetition of low-frequency word pairs significantly attenuated the post-second
      word event-related desynchronization in the theta-alpha (5-15 Hz) bands, at 200
      600 ms of post-second word stimulus onset. Peak significance between repeated
      high and low frequency words was evident at approximately 365-465 ms of
      posttarget onset. This finding has implications for: (i) the role of theta-alpha
      event-related desynchronization in lexical representation and access, (ii) the
      study of repetition suppression in the spectral-temporal domain, and (iii) the
      connection of neuronal repetition suppression with behavioral effects of
      repetition priming.

PMID- 21968324
TI  - Object and spatial visualizers have different object-processing patterns: 
      behavioral and ERP evidence.
AB  - Both behavioral and neurophysiological evidence shows the advantage of object
      visualizers in object-related tasks relative to spatial visualizers. It is still
      unclear, in which stage the advantage appears. In this study, a behavioral
      experiment revealed that spatial visualizers' performance decreased evidently
      from short delay to long delay in a high-load condition, but object visualizers
      performed stably. In addition, an event-related potential experiment found the
      slow cortical potentials for the spatial visualizer to be more negative in
      relation to object visualizers in the 1800-3800 ms stage, although spatial
      visualizers performed worse than the object visualizers. Therefore, the
      processing advantage of object visualizers, which is caused by the higher neural
      efficiency of object visualizers than spatial visualizers in object tasks, seems
      to be at the retention stage rather than the encoding stage.

PMID- 21968325
TI  - Functional and phylogenetic diversity of root-associated bacteria of Ajuga
      bracteosa in Kangra valley.
AB  - Present study investigates the cultivable diversity of root-associated bacteria
      from a medicinal plant Ajuga bracteosa in the Kangra valley, in order to
      determine their plant growth promoting (PGP) and biotechnological potential. The
      plant was found to exhibit a positive rhizosphere effect of 1.3-1.5. A total of
      123 morphologically different bacteria were isolated from the rhizospheric soil
      and roots of the plant. Medium composition was found to have significant effect
      on the composition of isolated bacterial populations. Majority of the
      rhizospheric soil isolates belonged to alpha- and gamma-Proteobacteria, with
      Pseudomonas constituting the most dominant species. Endophytic bacterial
      community, on other hand, consisted almost exclusively of Firmicutes. Majority of
      the isolates showed PGP activity by producing siderophores and indole acetic
      acid. Several isolates were found to exhibit very high antioxidant activity in
      the culture medium. A significant proportion of isolates also demonstrated other
      ecologically important activities like phosphate solubilization, nitrogen
      fixation, and production of hydrolytic enzymes including amylase, protease,
      lipase, chitinase, cellulase, pectinase and phosphatase. Firmicutes were found to
      be metabolically the most versatile group and performed multiple enzyme
      activities. This is the first systematic study of culturable bacterial community
      from the rhizosphere of A. bracteosa, particularly in the Kangra valley region.

PMID- 21968326
TI  - The mitochondrial ND1 3308T>C mutation may not be associated with left
      ventricular hypertrabeculation/noncompaction.

PMID- 21968327
TI  - Rapidly progressive renal disease as part of Wolfram syndrome in a large inbred
      Turkish family due to a novel WFS1 mutation (p.Leu511Pro).
AB  - Wolfram syndrome, also named "DIDMOAD" (diabetes insipidus, diabetes mellitus,
      optic atrophy, and deafness), is an inherited association of juvenile-onset
      diabetes mellitus and optic atrophy as key diagnostic criteria. Renal tract
      abnormalities and neurodegenerative disorder may occur in the third and fourth
      decade. The wolframin gene, WFS1, associated with this syndrome, is located on
      chromosome 4p16.1. Many mutations have been described since the identification of
      WFS1 as the cause of Wolfram syndrome. We identified a new homozygous WFS1
      mutation (c.1532T>C; p.Leu511Pro) causing Wolfram syndrome in a large inbred
      Turkish family. The patients showed early onset of IDDM, diabetes insipidus,
      optic atrophy, sensorineural hearing impairment and very rapid progression to
      renal failure before age 12 in three females. Ectopic expression of the wolframin
      mutant in HEK cells results in greatly reduced levels of protein expression
      compared to wild-type wolframin, strongly supporting that this mutation is
      disease-causing. The mutation showed perfect segregation with disease in the
      family, characterized by early and severe clinical manifestations.

PMID- 21968328
TI  - Is targeting eNOS a key mechanistic insight of cardiovascular defensive
      potentials of statins?
AB  - Statins are widely used in the treatment of dyslipidemia and associated
      cardiovascular abnormalities including atherosclerosis, hypertension and coronary
      heart disease. Needless to mention, statins have cholesterol-lowering effects by
      means of inhibiting 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, a rate
      limiting enzyme of cholesterol biosynthesis. Besides cholesterol-lowering
      effects, statins possess pleiotropic anti-inflammatory, anti-oxidant, anti
      platelet and anti-fibrotic properties, which may additionally play imperative
      roles in statins-mediated cardiovascular protection. However, the precise
      mechanisms involved in the cardiovascular defensive potential of statins have not
      completely been elucidated. Intriguingly, a considerable number of studies
      demonstrated the potential modulatory role of statins on endothelial nitric oxide
      synthase (eNOS), a key enzyme involved in the regulation of cardiovascular
      function by generating endothelium-derived relaxing factor (often represented
      'nitric oxide'). Worthy of note is that vascular generation of nitric oxide has
      beneficial anti-inflammatory, anti-platelet and vasodilatory actions. The
      upregulation of eNOS by statins is mediated through inhibition of synthesis of
      isoprenoids and subsequent prevention of isoprenylation of small GTPase Rho,
      whereas statin-induced activation of eNOS is mediated through activation of
      phosphotidylinositol-3-kinase (PI3K)/protein kinase B (PKB/Akt) signals.
      Additionally, statins enhance eNOS activation by abrogating caveolin-1 expression
      in vascular endothelium. In light of this view-point, we suggest in this review
      that eNOS upregulation and activation, in part, could play a fundamental role in
      the cardiovascular defensive potential of statins. The eNOS modulatory role of
      statins may have an imperative influence on the functional regulation of
      cardiovascular system and may offer new perspectives for the better use of
      statins in ameliorating cardiovascular disorders.

PMID- 21968329
TI  - Neutrophil-lymphocyte ratio as a predictor of adverse outcomes of acute
      pancreatitis.
AB  - BACKGROUND: Most acute pancreatitis risk scoring systems use total white blood
      cell counts (WBC) as one of the risk factors. The value of the neutrophil
      lymphocyte ratio (NLR) to predict the severity of acute pancreatitis has not been
      previously evaluated. METHODS: This observational study included 283 patients
      admitted to a tertiary center between 2004 and 2007. The patients were arranged
      into tertiles according to NLR and WBC values. The primary outcomes were
      intensive care unit (ICU) admission and length of stay (LOS) in the hospital.
      RESULTS: According to NLR tertiles, patients in the 3rd tertile (NLR >=7.6) had
      significantly more ICU admissions (17 vs. 2.2%, p < 0.0001) and longer average
      LOS (6.2 vs. 4.2 days, p < 0.002) compared with those in the 1st tertile (NLR
      <3.6). According to WBC tertiles, patients in the 3rd tertile had more ICU
      admissions (12.6 vs. 6.2%, p = 0.12) and a longer average LOS (5.8 vs. 4.4 days,
      p = 0.059) compared to patients in the 1st WBC tertile, but this did not reach
      statistical significance. In the multivariate model including NLR, WBC and other
      predictors, only NLR tertiles (p < 0.0262) and modified early warning scores (p <
      0.0025) were significant predictors of ICU admission. Likewise, in the
      multivariate model of LOS, only NLR and glucose level were significant predictors
      of longer LOS (p < 0.0161 and p < 0.0053, respectively). CONCLUSION: NLR is
      superior to total WBC in predicting adverse outcomes of acute pancreatitis.
      According to our data, we suggest using the NLR cutoff value of >4.7 as a simple
      indicator of severity in patients presenting with acute pancreatitis. and IAP.

PMID- 21968331
TI  - The role of bone marrow-derived adult stem cells in a transgenic mouse model of
      allergic asthma.
AB  - BACKGROUND: Asthmatic airway remodeling is an abnormal injury/repair process of
      the small airways caused by chronic inflammation in which the quantities of
      multiple cells increase dramatically. However, the origin of these proliferative
      cells is still undetermined. OBJECTIVE: The aim of this study was to examine
      whether bone marrow (BM)-derived adult stem cells are responsible for the
      proliferative cells in asthmatic airway remodeling. METHODS: Adult mice were
      durably engrafted with BM isolated from green fluorescent protein (GFP)
      transgenic mice. Using GFP BM chimera mice, an ovalbumin (OVA)-induced chronic
      asthma mouse model was established. The distribution of BM-derived GFP+ cells in
      the lungs of chronic asthma mice was detected by fluorescence microscopy. The
      phenotype of BM-derived GFP+ cells in the lung tissues of chronic asthma mice was
      analyzed by flow cytometry. RESULTS: BM chimera mice were successfully generated,
      with no detectable radioactive inflammation observed. Using BM chimera mice, we
      established a mouse model of chronic asthma characterized by a significant
      increase in the thickness of the airway subepithelial basement membrane and
      smooth muscle layers. OVA treatment caused many GFP+ cells to appear at sites of
      small airway inflammation. The extravascular localization of some GFP+ cells and
      their morphology were not consistent with leukocytes. Flow cytometric analysis of
      lung cells revealed a significant increase in type I collagen (Col I)+GFP+ cells
      and alpha-smooth muscle actin (alpha-SMA)+GFP+ cells in OVA-treated GFP BM
      chimera mice. CONCLUSIONS: Considerable numbers of Col I- and alpha-SMA-producing
      cells originated from BM in the lung tissues of mice with OVA-induced chronic
      asthma.

PMID- 21968330
TI  - Pre-operative planning for mandibular reconstruction - a full digital planning
      workflow resulting in a patient specific reconstruction.
AB  - OBJECTIVES: Reconstruction of large mandiblular defects following ablative
      oncologic surgery could be done by using vascularized bone transfer or, more
      often, primarily with simultaneous or delayed bone grafting, using load bearing
      reconstruction plates. Bending of these reconstruction plates is typically
      directed along the outer contour of the original mandible. Simultaneously or in a
      second operation vascularized or non-vascularized bone is fixed to the
      reconstruction plate. However, the prosthodontic-driven backward planning to ease
      bony reconstruction of the mandible in terms of dental rehabilitation using
      implant-retained overdentures might be an eligible solution. The purpose of this
      work was to develop, establish and clinically evaluate a novel 3D planning
      procedure for mandibular reconstruction. MATERIALS AND METHODS: Three patients
      with tumors involving the mandible, which included squamous cell carcinoma in the
      floor of the mouth and keratocystic odontogenic tumor, were treated surgically by
      hemimandibulectomy. RESULTS: In primary alloplastic mandible reconstruction,
      shape and size of the reconstruction plate could be predefined and prebent prior
      to surgery. CLINICAL RELEVANCE: This study provides modern treatment strategies
      for mandibular reconstruction.

PMID- 21968332
TI  - Frequent fever episodes and the risk of febrile seizures: the Generation R study.
AB  - AIM: To examine the association between the number of fever episodes and the risk
      of febrile seizures. METHODS: This study was embedded in a population-based
      prospective cohort study from early foetal life onwards. Information about the
      occurrence of febrile seizures and fever episodes was collected by questionnaires
      at the ages of 12, 24 and 36 months. Analyses were based on 3033 subjects. The
      risk of febrile seizures was compared between children with frequent fever
      episodes (>2 per year), and children with only 1 or 2 fever episodes per year.
      RESULTS: The frequency of fever episodes was not associated with the risk of
      febrile seizures in the age range of 6-12 months. In the second and third year of
      life, having more than 2 fever episodes was associated with an increased risk of
      febrile seizures (odds ratios 2.02 [95% confidence interval 1.13-3.62] and 2.29
      [95% confidence interval 1.00-5.24], respectively). In the age range between 6
      and 36 months, we observed a significant trend between the frequency of fever
      episodes (<2, 3-4 or >4 per year) and the risk of febrile seizures (p-value for
      trend < 0.001). The association between the number of fever episodes and the
      occurrence of febrile seizures was stronger for children with recurrent febrile
      seizures. CONCLUSION: Frequent fever episodes are associated with an increased
      risk of febrile seizures in the second and third years of life. Further studies
      are needed to identify the mechanisms underlying this association.

PMID- 21968333
TI  - Mercury and methylmercury concentrations in Mediterranean seafood and surface
      sediments, intake evaluation and risk for consumers.
AB  - Total mercury and methylmercury concentrations were measured in sediments and
      marine organisms from the Taranto Gulf to understand their distribution and
      partitioning. Sediment concentrations ranged from 0.036 to 7.730 mg/kg (mean:
      2.777 mg/kg d.w.) and from 1 to 40 MUg/kg (mean: 11 MUg/kg d.w.) for total
      mercury (THg) and methylmercury (Me-Hg), respectively. In mollusks THg ranged
      from n.d. to 1870 MUg/kg d.w. while in fish from 324 to 1740 MUg/kg d.w. Me-Hg
      concentrations in fish ranged from 190 to 1040 MUg/kg d.w. and from n.d. to 1321
      MUg/kg d.w. in mollusks. THg exceeded the maximum level fixed by the European
      Commission (0.5 mg/kg w.w.) only in gastropod Hexaplex t. The calculated weekly
      intake was in many cases over the Provisional Tolerable Weekly Intake established
      by EFSA for all edible species. These results seem to indicate that dietary
      consumption of this seafood implicates an appreciable risk for human health.

PMID- 21968334
TI  - Mercury, lead and cadmium levels in the urine of 170 Spanish adults: a pilot
      human biomonitoring study.
AB  - Human biomonitoring is a well-recognized tool for estimating the exposure of
      human populations to environmental pollutants. However, information regarding
      biomarker concentrations of many environmental chemicals in the general
      population is limited for many countries. The Spanish Environment Ministry has
      recently funded a human biomonitoring study on the Spanish general population.
      This study aims to determine reference levels for several biomarkers, especially
      heavy metals, persistent organic pollutants (POPs) and cotinine, in urine, whole
      blood, serum and hair, and will involve 2000 volunteers throughout Spain. Samples
      were taken during 2009-2010 and analyses are currently underway. The results
      presented herein were obtained in a pilot study carried out in the Madrid region.
      The study group comprised 170 volunteers, of which 79% were female and 21% male
      (age: 23-66 years). All participants were asked to complete a questionnaire
      regarding diet and living habits and provides a morning urine sample. The
      geometric means for total mercury (Hg), lead (Pb) and cadmium (Cd) were 1.23,
      1.11 and 0.25 MUg/g creatinine, respectively. Levels of Pb and Hg were higher
      than those reported for the general population in the USA and Germany, whereas Cd
      was in the same range (CDC, 2009; Becker et al., 2003). The values reported here
      are similar to those reported in other Spanish studies.

PMID- 21968335
TI  - Pollution gets personal! A first population-based human biomonitoring study in
      Austria.
AB  - Humans are exposed to a broad variety of man-made chemicals. Human biomonitoring
      (HBM) data reveal the individual body burden irrespective of sources and routes
      of uptake. A first population-based study was started in Austria in 2008 and was
      finished at the end of May 2011. This cross sectional study aims at documenting
      the extent, the distribution and the determinants of human exposure to industrial
      chemicals as well as proving the feasibility of a representative HBM study.
      Overall, 150 volunteers (50 families) were selected by stratified random
      sampling. Exposure to phthalates, trisphosphates, polybrominated diphenyl ethers
      (PBDE), bisphenol A (along with nonyl- and octyl phenol) and methyl mercury was
      assessed. Sixteen of 18 PBDE determined were detected above the limit of
      quantification (LOQ) in blood samples with #153 and #197 the most abundant
      species. Bisphenol A in urine was measured in a subsample of 25 with only 4
      samples found above the LOQ. In 3 of 100 urine samples at least one of 8
      trisphosphate compounds assessed was above the LOQ. These first analytical
      results of the human biomonitoring data show that the body burden of the Austrian
      population with respect to the assessed compounds is comparable to or even lower
      than in other European countries. Overall, the study revealed that in order to
      develop a feasible protocol for representative human biomonitoring studies
      procedures have to be optimized to allow for non-invasive sampling of body
      tissues in accordance with the main metabolic pathways. Procedures of
      participants' recruitment were, however, labor intensive and have to be improved.

PMID- 21968336
TI  - The new danger of thirdhand smoke: why passive smoking does not stop at
      secondhand smoke.

PMID- 21968337
TI  - Improved therapeutic entities derived from known generics as an unexplored source
      of innovative drug products.
AB  - With a New Drug Application (NDA) innovative drug therapies are reaching the
      market in a specific dosage form for one or more clinically proven indications of
      which after expiration of the patent or the data exclusivity copies are launched
      using Abbreviated New Drug Applications (ANDA). Advanced therapies that emerged
      from launched molecules during their product life-cycle have gained considerable
      attention as clinical practice provides evidence for additional therapeutic
      values, patient centric delivery systems show improved therapeutic outcomes or
      emerging technologies offer efficiency gains in manufacturing or access to
      emerging markets. The USA and European regulatory framework has set reasonable
      regulations in place for these "Supergenerics" or "hybrid" applications. While
      these regulations are relatively recent the pharmaceutical industry is just
      starting to use this route for their product development and life-cycle
      management. From a clinical perspective the potential for advanced product
      development have been demonstrated. Yet, there is still a lag of common
      understanding between the different stakeholders regarding the development,
      application process and commercial incentive in developing enhanced therapeutic
      entities based on existing drug products for the market.

PMID- 21968338
TI  - Current status and approaches to developing press-coated chronodelivery drug
      systems.
AB  - The past several decades have seen the development of many controlled-release
      preparations featuring constant release rates to maintain drug concentrations in
      the human body, regardless of the patient's physiological condition. However,
      long-term constant drug concentrations in the blood and tissue can cause problems
      such as resistance, tolerability, and drug side effects. People vary considerably
      in their physiological and biochemical conditions during any 24 h period, due to
      the circadian rhythm, and thus, the constant delivery of a drug into the body
      seems both unnecessary and undesirable. If the drug release profile mimics a
      living system's pulsatile hormone secretion, then it may improve drug efficacy,
      and reduce the toxicity of a specific drug administration schedule. Medication
      and treatments provided according to the body's circadian rhythms will result in
      better outcomes. This may be provided by a chronopharmaceutical dosage regimen
      with pulsatile release that matches the circadian rhythm resulting from a disease
      state, so optimizing the therapeutic effect while minimizing side effects. The
      press coating technique is a simple and unique technology used to provide tablets
      with a programmable lag phase, followed by a fast, or rate-controlled, drug
      release after administration. The technique offers many advantages, and no
      special coating solvent or coating equipment is required for manufacturing this
      type of tablet. The present review article introduces chronopharmaceutical press
      coated products from a patient physiological needs perspective. The contents of
      this article include biological rhythms and pulsatile hormone secretion in
      humans, the reasons for using pulsatile drug delivery for disease treatment,
      recent chronopharmaceutical preparations appearing on the market, updated
      compilation of all research articles and press-coated delivery techniques,
      factors affecting the performance and drug release characteristics of press
      coated delivery systems, and recent challenges for the press coating technique.
      We also provide a brief overview of press-coating approaches intended for
      chronotherapy.

PMID- 21968339
TI  - Depressive symptoms and the implicit evaluation of alcohol: the moderating role
      of coping motives.
AB  - BACKGROUND: Depressive symptoms in college students have been associated with a
      number of indices of hazardous drinking. Investigators have utilized a variety of
      experimental paradigms to better understand the cognitive-motivational mechanisms
      that may underlie this association. Implicit cognition studies have provided
      increasing support for the view that coping motives may moderate the association
      between negative affect and the incentive value of alcohol. However, less is
      known about how symptoms of depression may be linked with implicit evaluative
      responses to alcohol. The current research sought to investigate the association
      between depressive symptoms and implicit evaluations of alcohol stimuli as
      measured by an evaluative priming task. METHODS: Eighty-two current drinkers
      completed assessments of depressive symptoms, alcohol use, and drinking motives
      before engaging in a computerized alcohol evaluative priming task. RESULTS:
      Analyses showed that the association between depressive symptoms and the positive
      implicit evaluation of alcohol was moderated by drinking motives, such that the
      positive association between depression and alcohol evaluation was stronger for
      students who had higher coping motives. CONCLUSIONS: These findings add to our
      understanding of how depressive symptoms may influence responses to alcohol and
      provide further support for the view that individual differences in coping
      motives may be a critical moderator of the association between depressive
      symptoms and alcohol-related cognitive motivational processes.

PMID- 21968340
TI  - The significance of perineural invasion in early-stage cervical cancer.
AB  - INTRODUCTION: Cervical cancer spreads directly and through lymphatic and vascular
      channels. Perineural invasion is an alternative method of spread. Several risk
      factors portend poor prognosis and inform management decisions regarding adjuvant
      therapy. OBJECTIVE: To evaluate the incidence and significance of PNI in early
      cervical cancer. METHODS: Retrospective chart review of early-stage cervical
      cancer patients (IA-IIA) from 1994 to 2009. RESULTS: One hundred ninety two
      patients were included, 24 with perineural invasion in the cervical stroma
      (cases) and 168 without (controls). The mean age of the cases was 53 years,
      versus 45.9 in the controls (P=0.01). PNI was associated with more adjuvant
      therapy (P=0.0001), a higher stage (P=0.005), a larger tumor size (>= 4 cm)
      (P<0.0001), lymphovascular space invasion (P=0.002), parametrial invasion
      (P<0.0001) and more tumor extension to the uterus (P=0.015). On multivariate
      analysis using an adjusted hazard ratio, risk factors for recurrence included
      grade (HR, 95% CI; 3.61, 1.38-9.41) and histopathology (HR, 95% CI; 2.85, 100
      8.09). Similarly, risk factors for death included grade (HR, 95% CI; 3.43, 1.24
      9.49) and histopathology (HR, 95% CI; 3.71, 1.03-13.33). Perineural invasion was
      not identified as an independent risk factor for either recurrence or death. The
      mean follow up time was 56 months. There was no significant difference in
      recurrence (P=0.601) or over-all survival (P=0.529) between cases and controls.
      CONCLUSION: While perineural invasion was found to be associated with multiple
      high-risk factors, it was not found to be associated with a worse prognosis in
      early cervical cancer.

PMID- 21968341
TI  - A cost analysis of postoperative management in endometrial cancer patients
      treated by robotics versus laparoscopic approach.
AB  - OBJECTIVE: The purpose of this study is to compare postoperative pain management
      and costs in endometrial cancer patients who had a robotic-assisted or
      laparoscopic-assisted hysterectomy. METHODS: This is a retrospective cohort study
      of all endometrial cancer patients from 9/2005 to 6/2010 who had a completed
      robotic-assisted or laparoscopic-assisted hysterectomy. All surgeries were
      performed by gynecologic oncologists on the da Vinci S surgical system.
      Demographic data, patient-recorded pain scores, pain-management interventions,
      and postoperative pain medication costs were compared. Data was analyzed using
      Student's t-tests and Pearson's chi(2) tests in SPSS. RESULTS: Two-hundred
      fifteen (101 robotic and 114 laparoscopic) patients met the inclusion criteria.
      There were no significant differences between the groups in age, BMI, clinical
      stage, comorbidities, lymph nodes retrieved, and the number of narcotic vs. non
      narcotic drug interventions administered. Robotic patients had a lower number of
      initial drug interventions (21 vs. 52; P<.001) and total drug interventions (162
      vs. 219; P<.001) than laparoscopic patients. Robotics had a lower initial pain
      score (2.1 vs. 3.0; P=.012). There was a 50% reduction in the pain medication
      cost on the day of surgery for robotic patients ($12.24 vs. $24.45; P<.01), and a
      56% cost reduction for the rest of their length of stay ($3.63 vs. $8.17; P<.01).
      CONCLUSION: Endometrial cancer patients who have robotic surgery experience less
      initial postoperative pain and have fewer drug interventions. The cost associated
      for their pain management represents a savings of greater than 50%. These factors
      demonstrate the value of robotic surgery in regard to postoperative pain
      management by delivering higher quality care at a lower cost.

PMID- 21968342
TI  - Endometrial cancer patients and compliance with genetic counseling: room for
      improvement.
AB  - INTRODUCTION: Immunohistochemistry (IHC) for the presence or absence of DNA
      mismatch repair (MMR) proteins in tumor samples is a quick and relatively
      inexpensive method to screen for Lynch syndrome (LS). At our institution we have
      found that >20% of patients lack expression of MMR proteins and >10% would be
      expected to benefit from genetic counseling (GC). However, compliance with
      referral to GC is poor. Therefore, we set out to analyze the reasons for
      noncompliance, hypothesizing that it could be due to a perception of a low risk
      for developing other cancers. METHODS: All patients with endometrial cancer
      between 2007 and 2009 were identified. Patients with absence of MMR protein
      expression who would be expected to benefit from GC were identified. These
      patients were sent a questionnaire assessing the utilization of GC services as
      well as their perception of LS and Lynch-associated cancers. RESULTS: Forty-seven
      patients out of 384 were identified who would have been expected to benefit from
      GC. Of the responders, 20 patients (77%) reported that they were referred by
      their physician for GC, of which 9 saw a genetic counselor, 8 had genetic
      testing, and 3 mutations were detected. The primary reason for not seeing a
      genetic counselor was no insurance coverage/cost of the visit followed by anxiety
      for the results. Nine patients stated that the patient/family did not want to
      know information regarding cancer risk. As compared to the general population 35%
      thought their risk of having LS was higher, 12% thought it was the same, 15%
      lower, and 38% was unsure. Forty-six percent of patients thought the risk of
      colon cancer was higher than background risk, and 26% thought it was the same.
      CONCLUSION: Most patients underestimate their risk of LS associated heritable
      cancer. Physicians should pay more attention to family history and IHC in order
      to refer patients appropriately. In addition, more verbal and written information
      may enable patients to accurately assess their cancer risk. This could further
      improve compliance with genetic counseling and detection of Lynch syndrome.

PMID- 21968343
TI  - Linear Solvation Energy Relationships as classifiers in non-target analysis--a
      capillary liquid chromatography approach.
AB  - For the identification of unknowns in environmental samples, Linear Solvation
      Energy Relationships (LSERs) are applied as classifiers for exclusion of
      candidate compounds with equal exact mass. By prediction of the Chromatographic
      Hydrophobicity Index (CHI) from retention time of the unknown compound on a
      gradient system using a C18 column and the description of interactions by LSER
      descriptors, an exclusion of isomers, with different retention behaviour and
      interaction terms is possible. The example of several isomers, with the empirical
      formula C12H10O2, demonstrates the application as classifier and indicates limits
      of this prognosis.

PMID- 21968344
TI  - High-purity isolation of anthocyanins mixtures from fruits and vegetables--a
      novel solid-phase extraction method using mixed mode cation-exchange
      chromatography.
AB  - Research on biological activity of anthocyanins requires the availability of high
      purity materials. However, current methods to isolate anthocyanins or anthocyanin
      mixtures are tedious and expensive or insufficient for complete isolation. We
      applied a novel cation-exchange/reversed-phase combination solid-phase extraction
      (SPE) technique, and optimized the use of water/organic buffer mobile phases to
      selectively separate anthocyanins. Crude extracts of various representative
      anthocyanin sources were purified with this technique and compared to 3 commonly
      used SPE techniques: C(18), HLB, and LH-20. Purified anthocyanin fractions were
      analyzed with high performance liquid chromatography (HPLC) coupled to photodiode
      array (PDA) and mass spectrometry (MS) detectors and by Fourier transform
      infrared (FT-IR) spectroscopy. The UV-visible chromatograms quantitatively
      demonstrated that our novel technique achieved significantly higher (P<0.05)
      anthocyanin purity than the C(18) cartridge, the next best method, for 11 of the
      12 anthocyanin sources tested. Among them, eight were purified to greater than
      99% purity (based on UV-visible chromatograms). The new method efficiently
      removed non-anthocyanin phenolics. MS and FT-IR results semi-quantitatively
      confirmed extensive reduction of impurities. Due to strong ionic interaction, our
      sorbent capacity was superior to others, resulting in the highest throughput and
      least use of organic solvents. This new methodology for isolation of anthocyanin
      mixtures drastically increased purity and efficiency while maintaining excellent
      recovery rate and low cost. The availability of high purity anthocyanin mixtures
      will facilitate anthocyanin studies and promote the application of anthocyanins
      in the food and nutraceutical industries.

PMID- 21968345
TI  - Derivatization of azaspiracid biotoxins for analysis by liquid chromatography
      with fluorescence detection.
AB  - Azaspiracids (AZAs) are an important group of regulated lipophilic biotoxins that
      cause shellfish poisoning. Currently, the only widely available analytical method
      for quantitation of AZAs is liquid chromatography-mass spectrometry (LC-MS).
      Alternative methods for AZA analysis are needed for detailed characterization
      work required in the preparation of certified reference materials (CRMs) and by
      laboratories not equipped with LC-MS. Chemical derivatization of the amine and
      carboxyl groups on AZAs was investigated for the purpose of facilitating analysis
      by LC with fluorescence detection (FLD). Experiments towards chemical
      modification of AZA1 at the amine achieved only limited success. Derivatization
      of the carboxyl group, on the other hand, proved successful using the 9
      anthryldiazomethane (ADAM) method previously applied to the okadaic acid (OA)
      group toxins. Extraction and clean-up methods were investigated for shellfish
      tissue samples and a post-reaction solid phase extraction procedure was developed
      for the AZA ADAM derivatives. Chromatographic separations were developed for the
      LC-FLD analysis of derivatized AZAs alone or in the presence of other derivatized
      toxins. This new analytical method for analysis of AZAs enabled verification of
      AZA1-3 concentrations in recently certified reference materials. The method
      demonstrated good linearity, repeatability and accuracy showing its potential as
      an alternative to LC-MS for measurement of AZAs.

PMID- 21968346
TI  - Fluoroalcohols as novel buffer components for basic buffer solutions for liquid
      chromatography electrospray ionization mass spectrometry: retention mechanisms.
AB  - Two fluoroalcohols--1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) and 1,1,1,3,3,3
      hexafluoro-2-methyl-2-propanol (HFTB)--were evaluated as volatile buffer acids in
      basic mobile phases for LC-ESI-MS determination of acidic and basic compounds.
      HFIP and HFTB as acidic buffer components offer interesting possibilities to
      adjust retention behavior of different analytes and expand the currently rather
      limited range of ESI-compatible buffer systems for basic mobile phases. Comparing
      with commonly used basic buffer components the fluoroalcohols did not suppress
      the ionization of the analytes, for several analytes ionization enhancement was
      observed. RP chromatographic retention mechanisms were evaluated and compared to
      traditional buffer system. All trends in retention of the acidic and basic
      analytes can be interpreted by the following model: the neutral fluoroalcohols
      are quite strongly retained by the stationary phase whereas their anions are less
      retained, thus their amount on the stationary phase is dependent on mobile phase
      pH; the anions of the fluoroalcohols form ion pairs in the mobile phase with the
      basic analytes; the fluoroalcohols on the stationary phase surface compete with
      acidic analytes thereby hindering their retention; the fluoroalcohols on the
      stationary phase bind basic analytes thereby favoring their retention.

PMID- 21968347
TI  - Microchip electrophoresis of bacteria using lipid-based liquid crystalline
      nanoparticles.
AB  - The aggregation and adhesion of bacterial cells is a serious disadvantage for
      electrophoretic separations of bacteria. In this study, lipid-based liquid
      crystalline nanoparticles were used as a pseudostationary phase to minimise the
      bacterial aggregation and adsorption to the inner walls of microchannels.
      Lactobacillus delbrueckii subsp. bulgaricus, Streptococcus thermophilus and
      Lactobacillus rhamnosus were selected as analytes and were separated by microchip
      electrophoresis (MCE) with laser-induced fluorescence (LIF) detection using 4.5
      mM tris(hydroxymethyl) aminomethane (TRIS)-4.5 mM boric acid-0.1 mM
      ethylenediaminetetraacetate (EDTA) (TBE) containing poly(ethylene oxide) (PEO)
      and lipid-based nanoparticles as the running buffer. The mechanism of lipid-based
      nanoparticles affecting bacterial adhesion and aggregation was discussed and
      supported by zeta potential experiments. Under the optimal conditions, the three
      species of bacteria were identified with patterned peaks. This proposed MCE
      method using lipid-based nanoparticles as running buffer additives was also used
      to analyse a real yogurt sample, and valuable bacterial information was obtained
      by the electropherograms.

PMID- 21968348
TI  - Multi-residue determination of the sorption of illicit drugs and pharmaceuticals
      to wastewater suspended particulate matter using pressurised liquid extraction,
      solid phase extraction and liquid chromatography coupled with tandem mass
      spectrometry.
AB  - Presented is the first comprehensive study of drugs of abuse on suspended
      particulate matter (SPM) in wastewater. Analysis of SPM is crucial to prevent the
      under-reporting of the levels of analyte that may be present in wastewater.
      Analytical methods to date analyse the aqueous part of wastewater samples only,
      removing SPM through the use of filtration or centrifugation. The development of
      an analytical method to determine 60 compounds on SPM using a combination of
      pressurised liquid extraction, solid phase extraction and liquid chromatography
      coupled with tandem mass spectrometry (PLE-SPE-LC-MS/MS) is reported. The range
      of compounds monitored included stimulants, opioid and morphine derivatives,
      benzodiazepines, antidepressants, dissociative anaesthetics, drug precursors, and
      their metabolites. The method was successfully validated (parameters studied:
      linearity and range, recovery, accuracy, reproducibility, repeatability, matrix
      effects, and limits of detection and quantification). The developed methodology
      was applied to SPM samples collected at three wastewater treatment plants in the
      UK. The average proportion of analyte on SPM as opposed to in the aqueous phase
      was <5% for several compounds including cocaine, benzoylecgonine, MDMA, and
      ketamine; whereas the proportion was >10% with regard to methadone, EDDP, EMDP,
      BZP, fentanyl, nortramadol, norpropoxyphene, sildenafil and all antidepressants
      (dosulepin, amitriptyline, nortriptyline, fluoxetine and norfluoxetine).
      Consequently, the lack of SPM analysis in wastewater sampling protocol could lead
      to the under-reporting of the measured concentration of some compounds.

PMID- 21968349
TI  - Screening and characterization of natural antioxidants in four Glycyrrhiza
      species by liquid chromatography coupled with electrospray ionization quadrupole
      time-of-flight tandem mass spectrometry.
AB  - Licorice, derived from the dried roots and rhizomes of several species of genus
      Glycyrrhiza L. (Leguminosae family), has been traditionally used in herbal
      medicine for over 4000 years. In recent years, the interest in antioxidative
      constituents in licorice has greatly increased. In this work, a new method based
      on 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) spiking test combined with HPLC
      coupled with electrospray ionization quadrupole time-of-flight tandem mass
      spectrometry (Q-TOF MS/MS) analysis was developed to screen and identify the
      antioxidants in licorice. The results of the method validation indicated that the
      developed method was reliable and repeatable. Compared with DPPH on-line method,
      the HPLC-Q-TOF MS/MS method combined with DPPH spiking test offered much higher
      sensitivity and resolution. Using this method, 35 radical scavengers were
      screened from four Glycyrrhiza species (G. inflata, G. glabra, G. pallidiflora
      and G. uralensis), and 21 of them were unambiguously or tentatively identified by
      HPLC-Q-TOF MS/MS. Among the 21 identified flavonoids, 10 compounds had been
      reported to possess antioxidative activities in the previous studies, and the
      radical scavenging activities of the other 11 compounds were reported for the
      first time. The effects of six purified flavonoids on DPPH radical and lipid
      peroxidation were evaluated for validation of the developed method. The results
      indicated that HPLC-Q-TOF MS/MS coupled with DPPH treatment is an efficient and
      powerful method to discover the potential antioxidative compounds from the
      complex natural product mixtures. In this study, the identified components with
      free radical scavenging activity, would help to explain the therapeutic benefit
      of licorice in the treatment of human disease associated with oxidative stress.

PMID- 21968350
TI  - Critical evaluation of methodology commonly used in sample collection, storage
      and preparation for the analysis of pharmaceuticals and illicit drugs in surface
      water and wastewater by solid phase extraction and liquid chromatography-mass
      spectrometry.
AB  - The main aim of this manuscript is to provide a comprehensive and critical
      verification of methodology commonly used for sample collection, storage and
      preparation in studies concerning the analysis of pharmaceuticals and illicit
      drugs in aqueous environmental samples with the usage of SPE-LC/MS techniques.
      This manuscript reports the results of investigations into several sample
      preparation parameters that to the authors' knowledge have not been reported or
      have received very little attention. This includes: (i) effect of evaporation
      temperature and (ii) solvent with regards to solid phase extraction (SPE)
      extracts; (iii) effect of silanising glassware; (iv) recovery of analytes during
      vacuum filtration through glass fibre filters and (v) pre LC-MS filter membranes.
      All of these parameters are vital to develop efficient and reliable extraction
      techniques; an essential factor given that target drug residues are often present
      in the aqueous environment at ng L(-1) levels. Presented is also the first
      comprehensive review of the stability of illicit drugs and pharmaceuticals in
      wastewater. Among the parameters studied are: time of storage, temperature and
      pH. Over 60 analytes were targeted including stimulants, opioid and morphine
      derivatives, benzodiazepines, antidepressants, dissociative anaesthetics, drug
      precursors, human urine indicators and their metabolites. The lack of stability
      of analytes in raw wastewater was found to be significant for many compounds. For
      instance, 34% of compounds studied reported a stability change >15% after only 12
      h in raw wastewater stored at 2  degrees C; a very important finding given that
      wastewater is typically collected with the use of 24 h composite samplers. The
      stability of these compounds is also critical given the recent development of so
      called 'sewage forensics' or 'sewage epidemiology' in which concentrations of
      target drug residues in wastewater are used to back-calculate drug consumption.
      Without an understanding of stability, under (or over) reporting of consumption
      estimations may take place.

PMID- 21968351
TI  - Simultaneous anion and cation exchange chromatography of whey proteins using a
      customizable mixed matrix membrane.
AB  - Membrane chromatography can overcome some of the limitations of packed bed column
      chromatography but preparation of adsorptive membranes usually involves complex
      and harsh chemical modifications. Mixed matrix membranes (MMMs) require only the
      physical incorporation of an ion exchange resin into the membrane polymer
      solution prior to membrane casting. An advantage of MMMs not previously exploited
      is that resins with differing adsorptive functionalities can be conveniently
      embedded within a single membrane at any desired ratio. This presents the
      opportunity to customize an adsorptive membrane to suit the expected protein
      profile of a raw feed stream e.g. bovine whey or serum. In this work, a novel
      mixed mode interaction MMM customized to extract all major proteins from bovine
      whey was synthesized in a single membrane by incorporating 42.5 wt% Lewatit MP500
      anionic resin and 7.5 wt% SP Sepharose cationic resin into an ethylene vinyl
      alcohol base polymer casting solution. The mixed mode MMM developed was able to
      bind both basic and acidic proteins simultaneously from whey, with binding
      capacities of 7.16+/-2.24 mg alpha-lactalbumin g(-1) membrane, 11.40+/-0.73 mg
      lactoferrin (LF)g(-1) membrane, 59.21+/-9.90 mg beta-lactoglobulin g(-1) membrane
      and 6.79+/-1.11 mg immunoglobulin Gg(-1) membrane (85 mg total protein g(-1)
      membrane) during batch fractionation of LF-spiked whey. A 1000 m(2) spiral-wound
      membrane module (200 L membrane volume, 1m(3) module volume) is predicted to be
      able to produce approximately 25 kg total whey protein per h.

PMID- 21968352
TI  - Continuous noninvasive ventilation delivered by a novel total face mask: a case
      series report.
AB  - Noninvasive ventilation (NIV) has been widely used to decrease the complications
      associated with tracheal intubation in mechanically ventilated patients. However,
      nasal ulcerations may occur when conventional masks are used for continuous
      ventilation. A total face mask, which has no  contact with the more sensitive
      areas of the face, is a possible option. We describe 3 patients with acute
      respiratory failure due to amyotrophic lateral sclerosis, who developed nasal
      bridge skin necrosis during continuous NIV, and one patient with post-extubation
      respiratory failure due  to a high spinal cord injury, who had facial trauma with
      contraindication for conventional mask use. The total face mask was very well
      tolerated by all the patients, and permitted safe and efficient continuous NIV
      for several days until the acute respiratory failure episode resolved. None  of
      the patients required endotracheal intubation during the acute episode.

PMID- 21968353
TI  - Differences in efficacy and cytokine profiles following echinocandin or liposomal
      amphotericin B monotherapy or combination therapy for murine pulmonary or
      systemic Aspergillus flavus infections.
AB  - Given the recent increase in aspergillosis caused by species other than
      Aspergillus fumigatus, micafungin, caspofungin, and liposomal amphotericin B (L
      AmBi) were investigated as monotherapy or combination therapy for murine systemic
      or pulmonary Aspergillus flavus infection. Treatment for 3 or 6 days was begun at
      24 h (intravenous [i.v.], 2.8 * 10(4) conidia) or 2 h (intranasal, 4.1 * 10(6) to
      6.75 * 10(6) conidia) postchallenge as follows: 5 or 10 mg/kg L-AmBi, 10 mg/kg
      caspofungin, 15 mg/kg micafungin, L-AmBi plus echinocandin, L-AmBi on days 1 to 3
      and echinocandin on days 4 to 6, or echinocandin on days 1 to 3 and L-AmBi on
      days 4 to 6. Mice were monitored for survival, fungal burden, serum or tissue
      cytokines, and lung histopathology. In the systemic infection, micafungin or
      caspofungin was more effective than L-AmBi in prolonging survival (P < 0.05), and
      L-AmBi was associated with significantly elevated serum levels of interleukin-6
      (IL-6), macrophage inflammatory protein 1alpha (MIP-1alpha), and IL-12 (P <
      0.05). In contrast, L-AmBi was significantly more effective than the
      echinocandins in reducing fungal growth in most tissues (P < 0.05). Concomitant
      therapies produced significantly enhanced survival, reduction in fungal burden,
      and low levels of proinflammatory cytokines, while antagonism was seen with some
      sequential regimens. In comparison, in the pulmonary infection, L-AmBi was
      significantly better (P < 0.05) than caspofungin or the combination of L-AmBi and
      caspofungin in prolonging survival and reducing lung fungal burden. Caspofungin
      stimulated high lung levels of IL-1alpha, tumor necrosis factor alpha (TNF
      alpha), and IL-6, with extensive tissue damage. In summary, systemic A flavus
      infection was treated effectively with L-AmBi plus micafungin or caspofungin
      provided that the drugs were administered concomitantly and not sequentially,
      while pulmonary A. flavus infection responded well to L-AmBi but not to
      caspofungin.

PMID- 21968354
TI  - Candida albicans infections in renal transplant recipients: effect of caspofungin
      on polymorphonuclear cells.
AB  - This study aimed to compare the caspofungin immunomodulating activities against
      Candida albicans on polymorphonuclear cells (PMNs) from renal transplant
      recipients (RTRs) and healthy subjects (HSs). RTR PMNs showed a significantly
      reduced fungicidal activity compared with that of HS PMNs. Addition of
      caspofungin to RTR PMNs significantly potentiated the yeast intracellular killing
      rate, achieving values similar to those observed for HS PMNs. These data show
      that caspofungin is suitable for invasive candidiasis treatment in patients with
      immune system-impaired components.

PMID- 21968355
TI  - Comparison of pharmacokinetics and safety of voriconazole intravenous-to-oral
      switch in immunocompromised children and healthy adults.
AB  - Voriconazole pharmacokinetics are not well characterized in children despite
      prior studies. To assess the appropriate pediatric dosing, a study was conducted
      in 40 immunocompromised children aged 2 to <12 years to evaluate the
      pharmacokinetics and safety of voriconazole following intravenous (IV)-to-oral
      (PO) switch regimens based on a previous population pharmacokinetic modeling: 7
      mg/kg IV every 12 h (q12h) and 200 mg PO q12h. Area under the curve over the 12-h
      dosing interval (AUC(0-12)) was calculated using the noncompartmental method and
      compared to that for adults receiving approved dosing regimens (6 -> 4 mg/kg IV
      q12h, 200 mg PO q12h). On average, the AUC(0-12) in children receiving 7 mg/kg IV
      q12h on day 1 and at IV steady state were 7.85 and 21.4 MUg . h/ml, respectively,
      and approximately 44% and 40% lower, respectively, than those for adults at 6 ->
      4 mg/kg IV q12h. Large intersubject variability was observed. At steady state
      during oral treatment (200 mg q12h), children had higher average exposure than
      adults, with much larger intersubject variability. The exposure achieved with
      oral dosing in children tended to decrease as weight and age increased. The most
      common treatment-related adverse events were transient elevated liver function
      tests. No clear threshold of voriconazole exposure was identified that would
      predict the occurrence of treatment-related hepatic events. Overall, voriconazole
      IV doses higher than 7 mg/kg are needed in children to closely match adult
      exposures, and a weight-based oral dose may be more appropriate for children than
      a fixed dose. Safety of voriconazole in children was consistent with the known
      safety profile of voriconazole.

PMID- 21968356
TI  - First NDM-positive Salmonella sp. strain identified in the United States.

PMID- 21968357
TI  - Reduction in fluoroquinolone use following introduction of ertapenem into a
      hospital formulary is associated with improvement in susceptibility of
      Pseudomonas aeruginosa to group 2 carbapenems: a 10-year study.
AB  - We examined the effect of the addition of ertapenem to our hospital formulary on
      the resistance of nosocomial Pseudomonas aeruginosa to group 2 carbapenems
      (imipenem, meropenem, and doripenem). This was a retrospective, observational
      study conducted between 1 January 2000 and 31 January 2009 at a large, tertiary
      care hospital. Autoregressive integrated moving average (ARIMA) regression models
      were used to evaluate the effect of ertapenem use on the susceptibility of
      Pseudomonas aeruginosa to group 2 carbapenems as well as on the use of the group
      2 carbapenems, ciprofloxacin, and other antipseudomonal drugs (i.e., tobramycin,
      cefepime, and piperacillin-tazobactam). Resistance was expressed as a percentage
      of total isolates as well as the number of carbapenem-resistant bacterial
      isolates per 10,000 patient days. Pearson correlation was used to assess the
      relationship between antibiotic use and carbapenem resistance. Following the
      addition of ertapenem to the formulary, there was a statistically significant
      decrease in the percentage of Pseudomonas aeruginosa isolates resistant to the
      group 2 carbapenems (P = 0.003). Group 2 carbapenem use and the number of
      carbapenem-resistant Pseudomonas aeruginosa isolates per 10,000 patient days did
      not change significantly over the time period. There was a large decrease in the
      use of ciprofloxacin (P = 0.0033), and there was a correlation of ciprofloxacin
      use with the percentage of isolates resistant to the group 2 carbapenems (rho =
      0.47, P = 0.002). We suspect that the improvement in susceptibility of
      Pseudomonas aeruginosa to group 2 carbapenems was related to a decrease in
      ciprofloxacin use.

PMID- 21968358
TI  - Pharmacokinetics of isoniazid, rifampin, and pyrazinamide in children younger
      than two years of age with tuberculosis: evidence for implementation of revised
      World Health Organization recommendations.
AB  - The World Health Organization (WHO) recently issued revised first-line
      antituberculosis (anti-TB) drug dosage recommendations for children. No
      pharmacokinetic studies for these revised dosages are available for children <2
      years. The aim of the study was to document the pharmacokinetics of the first
      line anti-TB agents in children <2 years of age comparing previous and revised
      WHO dosages of isoniazid (INH; 5 versus 10 mg/kg/day), rifampin (RMP; 10 versus
      15 mg/kg/day), and pyrazinamide (PZA; 25 versus 35 mg/kg/day) and to investigate
      the effects of clinical covariates, including HIV coinfection, nutritional
      status, age, gender, and type of tuberculosis (TB), and the effect of NAT2
      acetylator status. Serum INH, PZA, and RMP levels were prospectively assessed in
      20 children <2 years of age treated for TB following the previous and the revised
      WHO dosage recommendations. Samples were taken prior to dosing and at 0.5, 1.5,
      3, and 5 h following dosing. The maximum drug concentration in serum (C(max)),
      the time to C(max) (t(max)), and the area under the concentration-time curve
      (AUC) were calculated. Eleven children had pulmonary and 9 had extrapulmonary TB.
      Five were HIV infected. The mean C(max) (MUg/ml) following the administration of
      previous/revised dosages were as follows: INH, 3.19/8.11; RMP, 6.36/11.69; PZA,
      29.94/47.11. The mean AUC (MUg.h/ml) were as follows: INH, 8.09/20.36; RMP,
      17.78/36.95; PZA, 118.0/175.2. The mean C(max) and AUC differed significantly
      between doses. There was no difference in the t(max) values achieved. Children
      less than 2 years of age achieve target concentrations of first-line anti-TB
      agents using revised WHO dosage recommendations. Our data provided supportive
      evidence for the implementation of the revised WHO guidelines for first-line anti
      TB therapy in young children.

PMID- 21968359
TI  - PhoQ mutations promote lipid A modification and polymyxin resistance of
      Pseudomonas aeruginosa found in colistin-treated cystic fibrosis patients.
AB  - Pseudomonas aeruginosa can develop resistance to polymyxin and other cationic
      antimicrobial peptides. Previous work has shown that mutations in the PmrAB and
      PhoPQ regulatory systems can confer low to moderate levels of polymyxin
      resistance (MICs of 8 to 64 mg/liter) in laboratory and clinical strains of this
      organism. To explore the role of PhoPQ in high-level clinical polymyxin
      resistance, P. aeruginosa strains with colistin MICs > 512 mg/liter that had been
      isolated from cystic fibrosis patients treated with inhaled colistin (polymyxin
      E) were analyzed. Probable loss-of-function phoQ alleles found in these cystic
      fibrosis strains conferred resistance to polymyxin. Partial and complete
      suppressor mutations in phoP were identified in some cystic fibrosis strains with
      resistance-conferring phoQ mutations, suggesting that additional loci can be
      involved in polymyxin resistance in P. aeruginosa. Disruption of chromosomal phoQ
      in the presence of an intact phoP allele stimulated 4-amino-l-arabinose addition
      to lipid A and induced transcription from the promoter of the pmrH (arnB) operon,
      consistent with the known role of this lipid A modification in polymyxin
      resistance. These results indicate that phoQ loss-of-function mutations can
      contribute to high-level polymyxin resistance in clinical strains of P.
      aeruginosa.

PMID- 21968360
TI  - Pharmacokinetics-pharmacodynamics of tigecycline in patients with community
      acquired pneumonia.
AB  - Exposure-response analyses for efficacy and safety were performed for tigecycline
      treated patients suffering from community-acquired pneumonia. Data were collected
      from two randomized, controlled clinical trials in which patients were
      administered a 100-mg loading dose followed by 50 mg of tigecycline every 12 h. A
      categorical endpoint, success or failure, 7 to 23 days after the end of therapy
      (test of cure) and a continuous endpoint, time to fever resolution, were
      evaluated for exposure-response analyses for efficacy. Nausea/vomiting, diarrhea,
      headache, and changes in blood urea nitrogen concentration (BUN) and total
      bilirubin were evaluated for exposure-response analyses for safety. For efficacy,
      ratios of the free-drug area under the concentration-time curve at 24 h to the
      MIC of the pathogen (fAUC(0-24):MIC) of >=12.8 were associated with a faster time
      to fever resolution; patients with lower drug exposures had a slower time to
      fever resolution (P = 0.05). For safety, a multivariable logistic regression
      model demonstrated that a tigecycline AUC above a threshold of 6.87 mg . hr/liter
      (P = 0.004) and female sex were predictive of the occurrence of nausea and/or
      vomiting (P = 0.004). Although statistically significant, the linear relationship
      between tigecycline exposure and maximum change from baseline in total bilirubin
      is unlikely to be clinically significant.

PMID- 21968361
TI  - First face composite-tissue transplant recipient successfully treated for
      cytomegalovirus infection with preemptive valganciclovir treatment.
AB  - Little is known about cytomegalovirus (CMV) infection after face transplantation,
      since only two of the 11 cases of face transplantation reported worldwide have
      documented a CMV infection after transplantation. Herein, we present the first
      report of a composite-tissue face allotransplant recipient at high risk for CMV
      infection (D(+)/R(-) [CMV serpositive donor positive/CMV seronegative receptor])
      undergoing preemptive treatment. Preemptive treatment was safe and effective for
      controlling CMV infection and thus promoting early acquisition of a CMV-specific
      immune response that protected the patient from late-onset CMV disease.

PMID- 21968362
TI  - Cyclopropyl carboxamides, a chemically novel class of antimalarial agents
      identified in a phenotypic screen.
AB  - Malaria is one of the deadliest infectious diseases in the world, with the
      eukaryotic parasite Plasmodium falciparum causing the most severe form of the
      disease. Discovery of new classes of antimalarial drugs has become an urgent task
      to counteract the increasing problem of drug resistance. Screening directly for
      compounds able to inhibit parasite growth in vitro is one of the main approaches
      the malaria research community is now pursuing for the identification of novel
      antimalarial drug leads. Very recently, thousands of compounds with potent
      activity against the parasite P. falciparum have been identified and information
      about their molecular descriptors, antiplasmodial potency, and cytotoxicity is
      publicly available. Now the challenges are how to identify the most promising
      chemotypes for further development and how best to progress these compounds
      through a lead optimization program to generate antimalarial drug candidates. We
      report here the first chemical series to be characterized from one of those
      screenings, a completely novel chemical class with the generic name cyclopropyl
      carboxamides that has never before been described as having antimalarial or other
      pharmacological activities. Cyclopropyl carboxamides are potent inhibitors of
      drug-sensitive and -resistant strains of P. falciparum in vitro and show in vivo
      oral efficacy in malaria mouse models. In the present work, we describe the
      biological characterization of this chemical family, showing that inhibition of
      their still unknown target has very favorable pharmacological consequences but
      the compounds themselves seem to select for resistance at a high frequency.

PMID- 21968363
TI  - Plasma drug activity assay for treatment optimization in tuberculosis patients.
AB  - Low antituberculosis (TB) drug levels are common, but their clinical significance
      remains unclear, and methods of measurement are resource intensive. Subjects
      initiating treatment for sputum smear-positive pulmonary TB were enrolled from
      Kibong'oto National TB Hospital, Tanzania, and levels of isoniazid, rifampin,
      ethambutol, and pyrazinamide were measured at the time of typical peak plasma
      concentration (C(2 h)). To evaluate the significance of the effect of observed
      drug levels on Mycobacterium tuberculosis growth, a plasma TB drug activity (TDA)
      assay was developed using the Bactec MGIT system. Time to detection of plasma
      cocultured M. tuberculosis versus time to detection of control growth was defined
      as a TDA ratio. TDA assays were later performed using the subject's own M.
      tuberculosis isolate and C(2 h) plasma from the Tanzanian cohort and compared to
      drug levels and clinical outcomes. Sixteen subjects with a mean age of 37.8 years
      +/- 10.7 were enrolled. Fourteen (88%) had C(2 h) rifampin levels and 11 (69%)
      had isoniazid levels below 90% of the lower limit of the expected range. Plasma
      spiked with various concentrations of antituberculosis medications found TDA
      assay results to be unaffected by ethambutol or pyrazinamide. Yet with a range of
      isoniazid and rifampin concentrations, TDA exhibited a statistically significant
      correlation with drug level and drug MIC, and a TDA of ~1.0 indicated the
      presence of multidrug-resistant TB. In Tanzania, low (<= 2.0) TDA was
      significantly associated with both lower isoniazid and rifampin C(2 h) levels,
      and very low (<= 1.5) TDA corresponded to a trend toward lack of cure. Study of
      TDA compared to additional clinical outcomes and as a therapeutic management tool
      is warranted.

PMID- 21968364
TI  - Identification of fusB-mediated fusidic acid resistance islands in Staphylococcus
      epidermidis isolates.
AB  - To understand the high prevalence of fusB genes in fusidic acid-resistant
      Staphylococcus epidermidis, analysis of resistance elements in 34 isolates was
      performed. First, sequence analysis of the aj1-LP-fusB region indicated that at
      least three types were present. Type I contained full-length aj1, type II
      contained a partial aj1 truncated from nucleotide position 93 to 421, and type
      III contained a more truncated aj1 that retained only the last 37 bp. Isolates
      with type I or type II aj1 displayed slightly higher levels of resistance to
      fusidic acid (MICs, 8 to 32 MUg/ml) than did those with type III aj1 (MICs, 4 to
      16 MUg/ml). Subsequent sequencing of the flanking regions of fusB from four
      selected isolates carrying different types of aj1-LP-fusB regions revealed that
      the fusB genes were all located on phage-related resistance islands (RIs),
      referred to as SeRI(fusB)(-2793), SeRI(fusB)(-704), SeRI(fusB)(-5907), and
      SeRI(fusB)(-7778), respectively. Among them, three islands (SeRI(fusB)(-2793),
      SeRI(fusB)(-704), and SeRI(fusB)(-5907)) were located downstream of groEL
      (corresponding to the 44-min position based on Staphylococcus aureus whole
      genomic sequences), and one (SeRI(fusB)(-7778)) was located downstream of rpsR
      (corresponding to the 8-min position). All of the RIs were inserted into
      integrase-recognized att sites. Among 34 isolates, the insertion sites of fusB
      RIs were mostly (28/34, 82%) located downstream of groEL and two were located
      downstream of rpsR, but four remained unidentified. The pulsotype distribution
      indicated that fusB-containing S. epidermidis isolates were heterogeneous. In
      conclusion, the fusB resistance determinant in S. epidermidis was highly
      associated with phage-related RIs. This is the first report of fusB RI in S.
      epidermidis.

PMID- 21968365
TI  - Relationship of agr expression and function with virulence and vancomycin
      treatment outcomes in experimental endocarditis due to methicillin-resistant
      Staphylococcus aureus.
AB  - The accessory gene regulator (agr) locus has been shown to be important for
      virulence in several animal models of Staphylococcus aureus infection. However,
      the role of agr in human infections, and specifically in antibiotic treatment, is
      controversial. Interestingly, agr dysfunction has been associated with reduced
      vancomycin responses. To systematically investigate the role of agr in virulence
      and treatment outcome in the context of endovascular infection, 10 well
      characterized vancomycin-susceptible methicillin-resistant S. aureus (MRSA)
      bloodstream isolates (5 agr-I [clonal complex 45, or CC45] and 5 agr-II [CC5])
      were studied for (i) agr function, (ii) RNAIII transcriptional profiles, (iii)
      agr locus sequences, (iv) intrinsic virulence and responses to vancomycin therapy
      in an experimental infective endocarditis (IE) model, and (v) in vivo RNAIII
      expression. Significant differences in agr function (determined by delta
      hemolysin activity) correlated with the time point of RNAIII transcription
      (earlier RNAIII onset equals increased agr function). Unexpectedly, four MRSA
      strains with strong delta-hemolysin activities exhibited significant resistance
      to vancomycin treatment in experimental IE. In contrast, five of six MRSA strains
      with weak or no delta-hemolysin activity were highly susceptible to vancomycin
      therapy in the IE model. agr sequence analyses showed no common single-nucleotide
      polymorphism predictive of agr functionality. In vivo RNAIII expression in
      cardiac vegetations did not correlate with virulence or vancomycin treatment
      outcomes in the IE model. Inactivation of agr in two strains with strong delta
      hemolysin activity did not affect virulence or the in vivo efficacy of
      vancomycin. Our findings suggest that agr dysfunction does not correlate with
      vancomycin treatment failures in this experimental IE model in two distinct MRSA
      genetic backgrounds.

PMID- 21968366
TI  - Bacteremia due to extended-spectrum-beta-lactamase-producing Aeromonas spp. at a
      medical center in Southern Taiwan.
AB  - Although extended-spectrum-beta-lactamase (ESBL)-producing aeromonads have been
      increasingly reported in recent years, most of them were isolates from case
      reports or environmental isolates. To investigate the prevalence of ESBL
      producers among Aeromonas blood isolates and the genes encoding ESBLs,
      consecutive nonduplicate Aeromonas blood isolates collected at a medical center
      in southern Taiwan from March 2004 to December 2008 were studied. The ESBL
      phenotypes were examined by clavulanate combination disk test and the cefepime
      clavulanate ESBL Etest. The presence of ESBL-encoding genes, including bla(TEM),
      bla(PER), bla(CTX-M), and bla(SHV) genes, was evaluated by PCR and sequence
      analysis. The results showed that 4 (2.6%) of 156 Aeromonas blood isolates, 1
      Aeromonas hydrophila isolate and 3 Aeromonas caviae isolates, expressed an ESBL
      producing phenotype. The ESBL gene in two A. caviae isolates was bla(PER-3),
      which was located in both chromosomes and plasmids, as demonstrated by Southern
      hybridization. Of four patients with ESBL-producing Aeromonas bacteremia, two
      presented with catheter-related phlebitis and the other two with primary
      bacteremia. Three patients had been treated with initial noncarbapenem beta
      lactams for 5 to 10 days, and all survived. In conclusion, ESBL producers exist
      among Aeromonas blood isolates, and clinical suspicion of ESBL production should
      be raised in treating infections due to cefotaxime-resistant Aeromonas isolates.

PMID- 21968367
TI  - Cyclopropavir susceptibility of cytomegalovirus DNA polymerase mutants selected
      after antiviral drug exposure.
AB  - Human cytomegalovirus (CMV) UL54 DNA polymerase (pol) mutants with known patterns
      of resistance to current antivirals ganciclovir (GCV), foscarnet (FOS), and
      cidofovir (CDV) were tested for cyclopropavir (CPV) susceptibility by a
      standardized reporter-based yield reduction assay. Exonuclease and A987G (region
      V) mutations at codons commonly associated with dual GCV-CDV resistance in
      clinical isolates paradoxically conferred increased CPV susceptibility. Various
      polymerase catalytic region mutations conferring FOS resistance with variable low
      grade GCV and CDV cross-resistance also conferred CPV resistance, with 50%
      effective concentration (EC(50)) increases of 3- to 13-fold. CPV EC(50) values
      against several pol mutants were increased about 2-fold by adding UL97 mutation
      C592G. Propagation of a CMV exonuclease mutant under CPV selected for pol
      mutations less often than UL97 mutations. In 21 experiments, one instance each of
      mutations E756D and M844V, which were shown individually to confer 3- to 4-fold
      increases in CPV EC(50), was detected. Unlike GCV and CDV, exonuclease mutations
      are not a preferred mechanism of CPV resistance, but mutations in and near pol
      region III may confer CPV resistance by affecting its recognition as an incoming
      base for DNA polymerization.

PMID- 21968368
TI  - Comparative effectiveness of aminoglycosides, polymyxin B, and tigecycline for
      clearance of carbapenem-resistant Klebsiella pneumoniae from urine.
AB  - Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an increasingly common cause
      of health care-associated urinary tract infections. Antimicrobials with in vitro
      activity against CRKP are typically limited to polymyxins, tigecycline, and
      often, aminoglycosides. We conducted a retrospective cohort study of cases of
      CRKP bacteriuria at New York-Presbyterian Hospital from January 2005 through June
      2010 to compare microbiologic clearance rates based on the use of polymyxin B,
      tigecycline, or an aminoglycoside. We constructed three active antimicrobial
      cohorts based on the active agent used and an untreated cohort of cases that did
      not receive antimicrobial therapy with Gram-negative activity. Microbiologic
      clearance was defined as having a follow-up urine culture that did not yield
      CRKP. Cases without an appropriate follow-up culture or that received multiple
      active agents or less than 3 days of the active agent were excluded. Eighty-seven
      cases were included in the active antimicrobial cohorts, and 69 were included in
      the untreated cohort. The microbiologic clearance rate was 88% in the
      aminoglycoside cohort (n = 41), compared to 64% in the polymyxin B (P = 0.02; n =
      25), 43% in the tigecycline (P < 0.001; n = 21), and 36% in the untreated (P <
      0.001; n = 69) cohorts. Using multivariate analysis, the odds of clearance were
      lower for the polymyxin B (odds ratio [OR], 0.10; P = 0.003), tigecycline (OR,
      0.08; P = 0.001), and untreated (OR, 0.14; P = 0.003) cohorts than for the
      aminoglycoside cohort. Treatment with an aminoglycoside, when active in vitro,
      was associated with a significantly higher rate of microbiologic clearance of
      CRKP bacteriuria than treatment with either polymyxin B or tigecycline.

PMID- 21968370
TI  - Derivatives of plant phenolic compound affect the type III secretion system of
      Pseudomonas aeruginosa via a GacS-GacA two-component signal transduction system.
AB  - Antibiotic therapy is the most commonly used strategy to control pathogenic
      infections; however, it has contributed to the generation of antibiotic-resistant
      bacteria. To circumvent this emerging problem, we are searching for compounds
      that target bacterial virulence factors rather than their viability. Pseudomonas
      aeruginosa, an opportunistic human pathogen, possesses a type III secretion
      system (T3SS) as one of the major virulence factors by which it secretes and
      translocates T3 effector proteins into human host cells. The fact that this human
      pathogen also is able to infect several plant species led us to screen a library
      of phenolic compounds involved in plant defense signaling and their derivatives
      for novel T3 inhibitors. Promoter activity screening of exoS, which encodes a T3
      secreted toxin, identified two T3 inhibitors and two T3 inducers of P. aeruginosa
      PAO1. These compounds alter exoS transcription by affecting the expression levels
      of the regulatory small RNAs RsmY and RsmZ. These two small RNAs are known to
      control the activity of carbon storage regulator RsmA, which is responsible for
      the regulation of the key T3SS regulator ExsA. As RsmY and RsmZ are the only
      targets directly regulated by GacA, our results suggest that these phenolic
      compounds affect the expression of exoS through the GacSA-RsmYZ-RsmA-ExsA
      regulatory pathway.

PMID- 21968369
TI  - Polyethylenimine is a strong inhibitor of human papillomavirus and
      cytomegalovirus infection.
AB  - Polyethylenimines are cationic polymers with potential as delivery vectors in
      gene therapy and with proven antimicrobial activity. However, the antiviral
      activity of polyethylenimines has not been addressed in detail thus far. We have
      studied the inhibitory effects of a linear 25-kDa polyethylenimine on infections
      with human papillomaviruses and human cytomegaloviruses. Preincubation of cells
      with polyethylenimine blocked primary attachment of both viruses to cells,
      resulting in a significant reduction of infection. In addition, the dissemination
      of human cytomegalovirus in culture cells was efficiently reduced by recurrent
      administration of polyethylenimine. Polyethylenimine concentrations required for
      inhibition of human papillomavirus and cytomegalovirus did not cause any
      cytotoxic effects. Polyethylenimines and their derivatives may thus be attractive
      molecules for the development of antiviral microbicides.

PMID- 21968372
TI  - Aminoacyl-tRNA synthetase inhibitors as potential antibiotics.
AB  - Increasing resistance to antibiotics is a major problem worldwide and provides
      the stimulus for development of new bacterial inhibitors with preferably
      different modes of action. In search for new leads, several new bacterial targets
      are being exploited beside the use of traditional screening methods. Hereto,
      inhibition of bacterial protein synthesis is a long-standing validated target.
      Aminoacyl-tRNA synthetases (aaRSs) play an indispensable role in protein
      synthesis and their structures proved quite conserved in prokaryotes and
      eukaryotes. However, some divergence has occurred allowing the development of
      selective aaRS inhibitors. Following an outline on the action mechanism of aaRSs,
      an overview will be given of already existing aaRS inhibitors, which are largely
      based on mimics of the aminoacyl-adenylates, the natural reaction intermediates.
      This is followed by a discussion on more recent developments in the field and the
      bioavailability problem.

PMID- 21968371
TI  - Triple-combination antiviral drug for pandemic H1N1 influenza virus infection in
      critically ill patients on mechanical ventilation.
AB  - A recent in vitro study showed that the three compounds of antiviral drugs with
      different mechanisms of action (amantadine, ribavirin, and oseltamivir) could
      result in synergistic antiviral activity against influenza virus. However, no
      clinical studies have evaluated the efficacy and safety of combination antiviral
      therapy in patients with severe influenza illness. A total of 245 adult patients
      who were critically ill with confirmed pandemic influenza A/H1N1 2009 (pH1N1)
      virus infection and were admitted to one of the intensive care units of 28
      hospitals in Korea were reviewed. Patients who required ventilator support and
      received either triple-combination antiviral drug (TCAD) therapy or oseltamivir
      monotherapy were analyzed. A total of 127 patients were included in our analysis.
      Among them, 24 patients received TCAD therapy, and 103 patients received
      oseltamivir monotherapy. The 14-day mortality was 17% in the TCAD group and 35%
      in the oseltamivir group (P = 0.08), and the 90-day mortality was 46% in the TCAD
      group and 59% in the oseltamivir group (P = 0.23). None of the toxicities
      attributable to antiviral drugs occurred in either group of our study, including
      hemolytic anemia and hepatic toxicities related to the use of ribavirin. Logistic
      regression analysis indicated that the odds ratio for the association of TCAD
      with 90-day mortality was 0.58 (95% confidence interval, 0.24 to 1.42; P = 0.24).
      Although this study was retrospective and did not provide virologic outcomes, our
      results suggest that the treatment outcome of the triple combination of
      amantadine, ribavirin, and oseltamivir was comparable to that of oseltamivir
      monotherapy.

PMID- 21968373
TI  - Hantzsch reaction: synthesis and characterization of some new 1,4-dihydropyridine
      derivatives as potent antimicrobial and antioxidant agents.
AB  - In the present study two new series of Hantzsch 1,4-dihydropyridine derivatives
      (1,4-DHPs) containing substituted pyrazole moiety (4a-f and 5a-f) were
      synthesized by the reaction of 3-aryl-1H-pyrazole-4-carbaldehydes with 1,3
      dicarbonylcompounds (ethylacetoacetate and methylacetoacetate) and ammonium
      acetate. The newly synthesized compounds were characterized by IR, NMR, mass
      spectral study and also by C, H, N analyses. New compounds were screened for
      their antimicrobial activity by well plate method (zone of inhibition).
      Antioxidant studies of the synthesized compounds were also performed by measuring
      the DPPH radical scavenging assay. Compounds 4c, 4e and 4f were found to be
      potent antibacterial and antioxidant agents. The acute oral toxicity study for
      the compounds 4c, 4e and 4f were carried out and the experimental studies
      revealed that compounds 4c and 4e is safe up to 3000 mg/kg and no death of
      animals were recorded. However in compound 4f, we found mortality above 2000 mg
      and also significant behavioral changes in experimental animals.

PMID- 21968374
TI  - Economic recession and mental health: an overview.
AB  - Effects of the current global economic downturn on population mental health will
      emerge in the years ahead. Judging from earlier experience of financial crises in
      various parts of the world, stresses associated with rising unemployment, poverty
      and social insecurity will lead to upward trends in many national suicide rates,
      as well as to less readily charted increase in the prevalence of psychiatric
      illness, alcohol-related disorders and illicit drug use. At the same time, mental
      health services are being cut back as part of government austerity programs.
      Budget cuts will thus affect psychiatric services adversely just when economic
      stressors are raising the levels of need and demand in affected populations.
      Proactive fiscal and social policies could, however, help to mitigate the health
      consequences of recession. Evidence- based preventive measures include active
      labor market and family support programs, regulation of alcohol prices and
      availability, community care for known high-risk groups, and debt relief
      projects. Economic mental health care could best be achieved, not by decimating
      services but by planning and deploying these to meet the needs of defined area
      populations.

PMID- 21968375
TI  - [Religion and suicide - part 1: the attitudes of religions towards suicide].
AB  - OBJECTIVE: While suicide is known in all human societies, national suicide rates
      vary to a high degree. Different interacting social, economic and biological
      factors may explain a part of the variance. Religions are supposed to have a
      protective effect against suicidal behavior. It is still unexplained, whether or
      not this holds true for all religions and whether this has an effect on the
      national suicide rates. For this purpose it is necessary to illustrate the
      positions of the single religions towards suicide in the context of their idea of
      a human being as well as their concepts of death and afterworld. METHOD: Our
      considerations are based upon a research on the religious- and culture-historical
      literature on this topic. RESULTS: None of the world religions argues for
      suicide, however, the degree of refusal is varying. Mosaic religions (Judaism,
      Christianity, Islam), which are based on the idea of a human being as the image
      of God, have a more pronounced position against suicide than Eastern religions
      with a concept of transmigration and rebirth. Atheistic positions, which are not
      attached to transcendent norms, show a broad range of opinions from radical
      refusal to cautious approval. CONCLUSIONS: The positions of the different
      religions towards suicide are leading to assumptions of their effect on national
      suicide rates that have to be tested empirically.

PMID- 21968376
TI  - [Religion and suicide - part 2: confessions, religiousness, secularisation and
      national suicide rates].
AB  - OBJECTIVE: National suicide rates differ remarkably. The influence of religion on
      the frequency of suicides was already stressed by Durkheim, however, character
      and dimension of this influence are still unclear. Our study claims to assess the
      association between (a) the distribution of believers of different religions, (b)
      the secularization, (c) the religiousness and the national suicide rates by
      gender. METHOD: Data of the distribution of religious confessions and of the
      religiousness of the inhabitants of the single countries were correlated with the
      national suicide rates and illustrated by means of Scatter/Dot-Plots. RESULTS:
      Independent of gender, low suicide rates were found in Islamic countries.
      Buddhist countries showed high suicide rates in women, and countries with a high
      percentage of inhabitants without confession high suicide rates in men. Only
      catholic countries showed an association between secularisation and suicide
      rates. In countries with a high proportion of religious inhabitants we found low
      suicide rates. CONCLUSIONS: Although none of the World religions support the
      human right of suicide, the mosaic religions of resurrection refuse suicide more
      strictly than the Eastern religions of reincarnation. All in all our study
      supports the hypothesis that religiousness can be seen as a protective factor
      against suicide.

PMID- 21968377
TI  - [Real-time monitoring in psychotherapy - methodology and casuistics].
AB  - BACKGROUND: Real-Time Monitoring in psychotherapy is a new method to increase
      quality and efficacy in psychotherapy. This internet-based information technology
      offers an online collection of psychotherapy-related data and allows insights
      into therapeutic patterns of change without any time-delay. The classical pre
      post-evaluation is completed by an assessment of therapeutic processes. Besides
      an internet-based data collection the Synergetic Navigation System (SNS)
      integrates different methods of nonlinear time series analysis and provides a
      visualization of results. METHOD: SNS is a new internet-based technology of data
      collection and data analysis. For illustration we present a single case study
      (avoidant personality disorder (DSM IV 301.82) with recurrent major depressive
      episodes) where SNS was applied in clinical practice (in-patient treatment). SNS
      results are used for therapy planning by repeated feedback interviews with the
      patients. RESULTS: Critical phases and nonlinearities of the ongoing self
      organization processes can be identified. In addition to the practical impact of
      real-time monitoring SNS allows for continuous process-outcome-research in
      naturalistic settings. Models of change processes (e.g. sudden gains) can be
      tested but also used as a interpretation frame of idiographic results.
      CONCLUSIONS: In every day practice SNS enhances transparency, self-efficacy of
      patients, and supports the motivation to change. Compliance of patients is high,
      and the data show high validity. Therefore as a future perspective SNS should
      become routine in clinical practice and be integrated in professional
      psychotherapy training.

PMID- 21968378
TI  - [Psychiatric day hospital - one year follow up].
AB  - OBJECTIVE: The psychiatric day hospital of the county hospital Neunkirchen was
      opened in 2003. All patients of the first year were followed up after one year to
      review and evaluate our support proposal. RESEARCH DESIGN: The data of all
      patients who were admitted in the first year were collected before admission, at
      discharge and after a 1 year follow up period. 57,7% also did psychological
      questionnaires about psychiatric symptoms, existential orientation, state of
      health, impairment and selfmanagement ability at all 3 dates. RESULTS: Almost all
      the patients (93%) utilized an after care offer and were still in aftercare
      treatment after on year. About 40% had no psychiatric episodes, 62% had no
      further admission to a psychiatric unit in the follow up period. We also found
      that the improvement of the psychiatric symptoms, existential orientation, state
      of health, impairment and selfmanagement ability which was achieved during the
      treatment was stable over the 1 year follow up period. CONCLUSION: The results of
      the one year follow up show that the concept of the psychiatric day hospital at
      Neunkirchen with two diagnose specific treatment groups seems to be successful
      regarding motivation for after care treatment and the stability of psychiatric
      symptoms in evidence of further admissions to a psychiatric unit.

PMID- 21968379
TI  - [Psychiatric day hospital - missing treatment start and early drop outs].
AB  - OBJECTIVE: Early drop outs are a common problem in day hospital treatment. In
      this article special focus is given to patient description and reasons for
      rejecting the programme after entrance evaluation and informed consent for the
      program and early drop outs within 7 days. RESEARCH DESIGN: The data of all
      consecutive patients of the first year were collected before admission, absent
      treatment start and early drop out. RESULTS: There were no differences found
      between the group of early drop outs and rejecters and the other patients who
      participated to the programme as planned regarding social data, diagnostic,
      severity, distance or feasibility of transportation. The only difference we could
      find in our data was that the rejecters group had significant more somatic
      diagnosis. CONCLUSION: We spend lot of time and personal resources on informed
      consent and selection before admission, which may be one reason for the low drop
      out rate. The possibilities of transfer to the inpatient unit or to somatic wards
      are necessary. In our experience it is helpful for treatment in a day hospital to
      cooperate with and be nearby a psychiatric department at a general hospital.

PMID- 21968380
TI  - [Qualitative methods in psychiatric research].
AB  - OBJECTIVE: This article addresses the usage of qualitative methods in psychiatric
      research and presents the qualitative approach in more detail. METHODS: Recent
      original empirical work of a German psychiatric journal was systematically
      reviewed. Methods used to collect and analyse the information are detailed.
      RESULTS: One third of the articles used a solely qualitative research design. One
      further article applied a combination of quantitative and qualitative approaches.
      Three kinds of the qualitative interviews were used (in depth, narrative and
      problem-focussed interview). Additionally, focus groups (group discussions) and
      qualitative content analysis were applied by studies. CONCLUSIONS: Qualitative
      approaches are an integral part of psychiatric research. Further work should
      assure to use adequate sampling strategies.

PMID- 21968381
TI  - [Dissociation (conversion) - malingering - antisocial personality disorder:
      differential diagnostic reflection on the basis of a case study].
AB  - In this case report we refer to the big challenge of making a diagnosis in a
      deliberate malingering in the field of mental disorders. We specifically describe
      the difficulty regarding the differentiation between a conversion disorder and
      malingering of a serial delinquent. For such a person avoiding criminal
      persecution is one of the most frequent reason to deceitfully simulate a mental
      illness. In this field, symptoms of conversion disorders exceed the average;
      furthermore, a great number of organic-neurological illnesses may appear to be
      very similar to a conversion disorder or in many cases a neurological disorder
      can actually be detected in the course of a somatic examination. A further
      obstacle for the differential diagnosis can be seen in the difficulty to discern
      it from factitious disorders. However, it is quite possible to discern the
      deliberate malingering of a mental disorder from a conversion disorder by means
      of the diligent diagnosis of a competent and experienced doctor/assessor who
      specialises.

PMID- 21968383
TI  - Unimpressive efficacy and unclear safety assessment of epidural cortical
      stimulation for refractory major depressive disorder.

PMID- 21968382
TI  - Facial reanimation of patients with neurofibromatosis type 2.
AB  - BACKGROUND: Neurofibromatosis type 2 (NF2) is a tumor suppressor syndrome defined
      by bilateral vestibular schwannomas. Facial paralysis, from either tumor growth
      or surgical intervention, is a devastating complication of this disorder and can
      contribute to disfigurement and corneal keratopathy. Historically, physicians
      have not attempted to treat facial paralysis in these patients. OBJECTIVE: To
      review our clinical experience with free gracilis muscle transfer for the purpose
      of facial reanimation in patients with NF2. METHODS: Five patients with NF2 and
      complete unilateral facial paralysis were referred to the facial nerve center at
      our institution. Charts and operative reports were reviewed; treatment details
      and functional outcomes are reported. RESULTS: Patients were treated between 2006
      and 2009. Three patients were men and 2 were women. The age of presentation of
      debilitating facial paralysis ranged from 12 to 50 years. All patients were
      treated with a single-stage free gracilis muscle transfer for smile reanimation.
      Each obturator nerve of the gracilis was coapted to the masseteric branch of the
      trigeminal nerve. Measurement of oral commissure excursions at rest and with
      smile preoperatively and postoperatively revealed an improved and nearly
      symmetric smile in all cases. CONCLUSION: Management of facial paralysis is often
      times overlooked when defining a care plan for NF2 patients who typically have
      multiple brain and spine tumors. The paralyzed smile may be treated successfully
      with single-stage free gracilis muscle transfer in the motivated patient.

PMID- 21968384
TI  - How does the trajectory of multimorbidity vary across Black, White, and Mexican
      Americans in middle and old age?
AB  - OBJECTIVES: This research examines intra- and interpersonal differences in
      multiple chronic conditions reported by Americans aged 51 and older for a period
      up to 11 years. It focuses on how changes in multimorbidity vary across White,
      Black, and Mexican Americans. METHODS: Data came from 17,517 respondents of the
      Health and Retirement Study (1995-2006) with up to 5 repeated observations.
      Hierarchical linear models were employed to analyze ethnic variations in temporal
      changes of reported comorbidities. FINDINGS: Middle-aged and older Americans have
      on average nearly 2 chronic diseases at the baseline, which increased to almost 3
      conditions in 11 years. White Americans differ from Black and Mexican Americans
      in terms of level and rate of change of multimorbidity. Mexican Americans
      demonstrate lower initial levels and slower accumulation of comorbidities
      relative to Whites. In contrast, Blacks showed an elevated level of
      multimorbidity throughout the 11-year period of observation, although their rate
      of change slowed relative to Whites. DISCUSSION: These results suggest that
      health differences between Black Americans and other ethnic groups including
      White and Mexican Americans persist in the trajectory of multimorbidity even when
      population heterogeneity is adjusted. Further research is needed concerning the
      impact of health disadvantages and differential mortality that may have occurred
      before middle age as well as exploring the role of nativity, the nature of self
      reported diseases, and heterogeneity underlying the average trajectory of
      multimorbidity for ethnic elders.

PMID- 21968385
TI  - Cohort differences and chronic disease profiles of differential disability
      trajectories.
AB  - OBJECTIVES: Research shows declining disability rates, but little is known about
      whether cohort differences are due to delayed onset, increased recovery, or
      reduced severity of impairment. Furthermore, disease is considered the proximate
      cause of disability yet chronic conditions rates are increasing, making it
      unclear whether the conditions predicting specific disability trajectories are
      changing. METHODS: We use a latent class analysis of disability trajectories and
      corresponding mortality with three birth cohorts of the National Long-Term Care
      Survey to determine how long-term experiences of disablement differ by cohort and
      chronic conditions. RESULTS: More recent cohorts were more likely to experience a
      decade free of disablement compared with all other disability trajectories.
      Sensory problems and hypertension correspond to trajectories of non-disablement,
      whereas hip fracture, stroke, arthritis, and diabetes predict more disabled
      experiences. DISCUSSION: Later life disability is measured nonparametrically to
      distinguish patterns among long-term trajectories. Findings suggest that more
      recent cohorts are more likely to forego or delay disability over a decade rather
      than experience prolonged periods of mild to severe disablement. Serious health
      events such as stroke, along with diabetes, characterize trajectories of high
      impairment, warranting future research.

PMID- 21968386
TI  - Synergistic interactions of saponins and monoterpenes in HeLa cells, Cos7 cells
      and in erythrocytes.
AB  - In phytomedicine complex extracts consisting of phenolics, monoterpenes or
      saponins are traditionally used. It is often impossible to attribute the
      biological activity of an extract to one or few compounds. As an explanation of
      the superior activity of extracts, a synergistic effect of combinations of active
      compounds has been suggested. Since lipophilic monoterpenes or saponins targeting
      the biomembrane usually accompany polar polyphenols in phytomedical preparations,
      we decided to investigate their effect as single substances and in combination to
      gain further insight into potential synergistic effects of herbal medicine.
      Combinations of the monoterpenes alpha-pinene, thymol and menthol with the
      monodesmosidic saponins digitonin, aescin, glycyrrhizic acid and Quillaja saponin
      demonstrated strong synergistic activity. The IC(50) of haemolysis was lowered by
      a factor of 10-100 from 316MUg/ml to 2MUg/ml for aescin, 157MUg/ml to 11MUg/ml
      for Quillaja saponins and 20MUg/ml to 3MUg/ml for digitonin when combined with
      thymol. A similar significant synergistic cytotoxicity occurred both in HeLa and
      Cos7 cells by combining the alpha-pinene, thymol and menthol with the saponins.
      The IC(50) of glycyrrhizic acid was lowered by a factor 100 from around 300MUg/ml
      to around 1-10MUg/ml and the IC(50) of aescin, digitonin and Quillaja saponins
      about the factor 10. Monoterpenes and monodesmosidic saponins have a common
      target, the biomembrane, which is present in all animal, fungal and bacterial
      cells. Disturbance of membrane fluidity and permeability is the mode of action.
      This activity is non-specific which makes it extremely difficult for bacteria and
      fungi to develop resistance. This explains the overall success of these molecules
      as defence chemicals in the plant kingdom. The synergistic effect of combinations
      of saponins with monoterpenes opens a complete new field of possible applications
      in medicine to overcome resistance in multidrug resistant microbial and human
      cell.

PMID- 21968387
TI  - Insulin-like growth factor-I and insulin-like growth factor binding protein-3
      cotreatment versus insulin-like growth factor-I alone in two brothers with growth
      hormone insensitivity syndrome: effects on insulin sensitivity, body composition
      and linear growth.
AB  - BACKGROUND/AIMS: Growth hormone insensitivity syndrome (GHIS) is caused by a
      defective growth hormone receptor (GHR) and is associated with insulin-like
      growth factor-I (IGF-I) deficiency, severely short stature and, from adolescence,
      fasting hyperglycemia and obesity. We studied the effects of treatment with IGF-I
      in either a 1:1 molar complex with IGFBP-3 (IGF-I/BP-3-Tx) or with IGF-I alone
      (IGF-I-Tx) on metabolism and linear growth. METHODS: Two brothers, compound
      heterozygous for a GHR gene defect, were studied. After 8 months without
      treatment, we examined the short- and long-term effects of IGF-I/BP-3-Tx and,
      subsequently, IGF-I-Tx on 12-hour overnight levels of IGF-I, GH, insulin, IGFBP
      1, insulin sensitivity by hyperinsulinemic euglycemic clamp, body composition by
      dual-energy X-ray absorptiometry and linear growth. RESULTS: Mean overnight
      levels of insulin decreased and IGFBP-1, a measure of hepatic insulin
      sensitivity, increased on both regimens, but was more pronounced on IGF-I-Tx.
      Insulin sensitivity by clamp showed no consistent changes. Lean body mass
      increased and abdominal fat mass decreased in both subjects on IGF-I-Tx. However,
      the changes were inconsistent during IGF-I/BP-3-Tx. Height velocity was low
      without treatment, increased slightly on IGF-I/BP-3-Tx and doubled on IGF-I-Tx.
      CONCLUSION: Both modalities of IGF-I improved determinants of hepatic insulin
      sensitivity, body composition and linear growth rate; however, IGF-I alone seemed
      to be more efficient.

PMID- 21968388
TI  - Management of delayed post-pancreaticoduodenectomy arterial bleeding:
      interventional radiological treatment first.
AB  - OBJECTIVE: To investigate the diagnosis and treatment of delayed post
      pancreaticoduodenectomy arterial bleeding (DPPAB). METHODS: Records of 336
      patients who underwent pancreaticoduodenectomy (PD) between January 2000 and
      December 2010 were retrospectively analyzed. Detailed data of patients with DPPAB
      were assessed by a thorough review of medical records. RESULTS: 14 patients
      developed DPPAB. The mean time interval between the initial surgery and DPPAB was
      33 days (range 7-72). Three patients experienced sentinel bleeding 5-8 days
      before DPPAB. All DPPAB patients had intra-abdominal septic complications before
      bleeding. The overall prevalence of success of angiography and transcatheter
      arterial embolization (TAE) was 85.7% (12/14), including 3 patients who achieved
      complete hemostasis by TAE after unsuccessful re-laparotomy. The prevalence of
      mortality of DPPAB was 28.6% (4/14). After hemostasis was achieved, intra
      abdominal septic complications were controlled by percutaneous catheter drainage
      or re-laparotomy with drain replacement. CONCLUSION: Angiography and TAE are
      recommended as the first-line diagnostic and treatment choice for DPPAB,
      respectively. Surgical intervention should be preserved to eliminate the cause of
      bleeding.

PMID- 21968389
TI  - DDT Paradox.

PMID- 21968392
TI  - An evaluation of aerobic and anaerobic sludges as start-up material for microbial
      fuel cell systems.
AB  - The operation of microbial fuel cells (MFCs) seeded with the same quantities of
      aerobic or anaerobic sludge has been compared. The two sludges consisted of mixed
      cultures obtained from the aerobic reactor and anaerobic digester, respectively,
      of a municipal Wastewater Treatment Plant (WWTP). Both the sludges were diluted
      with their sedimentation supernatant to avoid modifying their metabolism. The
      results show that the type of sludge has a major impact on the performance of the
      system. Seeding an MFC with anaerobic acclimated sludge leads to a more rapid
      start-up of electricity production and the absence of a lag period. In the MFC
      seeded with anaerobic sludge, the steady-state operation conditions were achieved
      in less than 10 days, while in the aerobic sludge-seeded MFC more than 20 days
      were necessary to achieve this regime. The anaerobic sludge also led to better
      performance of the MFC. Thus, maximum power densities above 300mWm(-2) were
      obtained for such systems (i.e. two times higher than that achieved with the
      aerobic sludge-seeded MFC in the same setup). This better performance is a direct
      consequence of the greater availability of Chemical Oxygen Demand (COD) in
      anaerobic sludge. However, the performance is not a consequence of the coulombic
      efficiency in the use of the COD to produce electricity because the aerobic
      sludge-seeded MFC doubles this figure with respect to the anaerobic sludge-seeded
      system.

PMID- 21968393
TI  - An improved system for the surface immobilisation of proteins on Bacillus
      thuringiensis vegetative cells and spores through a new spore cortex-lytic enzyme
      anchor.
AB  - An improved surface-immobilisation system was engineered to target heterologous
      proteins onto vegetative cells and spores of Bacillus thuringiensis plasmid-free
      recipient strain BMB171. The sporulation-dependent spore cortex-lytic enzyme from
      B. thuringiensis YBT-1520, SceA, was expressed in vegetative cells and used as
      the surface anchoring motif. Green fluorescent protein (GFP) and a Bacillus endo
      beta-1,3-1,4-glucanase (BglS) were used as the fusion partners to test the
      binding efficiency and the functional activities of immobilised surface proteins.
      The surface localisation of the SceA-GFP fusion protein on vegetative cells and
      spores was confirmed by Western blot, immunofluorescence microscopy and flow
      cytometry. The GFP fluorescence intensity from both vegetative cells and spores
      was measured and compared to a previously characterised surface display system
      using a peptidoglycan hydrolase anchor (Mbg). Results demonstrated comparable
      efficiency of SceA- and Mbg-mediated immobilisation on vegetative cells but a
      more efficient immobilisation on spores using the SceA anchor, suggesting SceA
      has greater potential for spore-based applications. The SceA protein was then
      applied to target BglS onto vegetative cells and spores, and the surface
      immobilisation was verified by the substantial whole-cell enzymatic activity and
      enhanced whole-spore enzymatic activity compared to vegetative cells. A dually
      active B. thuringiensis vegetative cell and spore display system could prove
      especially valuable for the development of regenerable and heat-stable
      biocatalysts that function under adverse environmental conditions, for example,
      an effective feed additive for improved digestion and nutrient absorption by
      livestock.

PMID- 21968396
TI  - Quantitation and analysis of the formation of HO-endonuclease stimulated
      chromosomal translocations by single-strand annealing in Saccharomyces
      cerevisiae.
AB  - Genetic variation is frequently mediated by genomic rearrangements that arise
      through interaction between dispersed repetitive elements present in every
      eukaryotic genome.  This process is an important mechanism for generating
      diversity between and within organisms(1-3).  The human genome consists of
      approximately 40% repetitive sequence of retrotransposon origin, including a
      variety of LINEs and SINEs(4).  Exchange events between these repetitive elements
      can lead to genome rearrangements, including translocations, that can disrupt
      gene dosage and expression that can result in autoimmune and cardiovascular
      diseases(5), as well as cancer in humans(6-9). Exchange between repetitive
      elements occurs in a variety of ways.  Exchange between sequences that share
      perfect (or near-perfect) homology occurs by a process called homologous
      recombination (HR).  By contrast, non-homologous end joining (NHEJ) uses little
      or-no sequence homology for exchange(10,11).  The primary purpose of HR, in
      mitotic cells, is to repair double-strand breaks (DSBs) generated endogenously by
      aberrant DNA replication and oxidative lesions, or by exposure to ionizing
      radiation (IR), and other exogenous DNA damaging agents.  In the assay described
      here, DSBs are simultaneously created bordering recombination substrates at two
      different chromosomal loci in diploid cells by a galactose-inducible HO
      endonuclease (Figure 1). The repair of the broken chromosomes generates
      chromosomal translocations by single strand annealing (SSA), a process where
      homologous sequences adjacent to the chromosome ends are covalently joined
      subsequent to annealing.  One of the substrates, his3-Delta3', contains a 3'
      truncated HIS3 allele and is located on one copy of chromosome XV at the native
      HIS3 locus. The second substrate, his3-Delta5', is located at the LEU2 locus on
      one copy of chromosome III, and contains a 5' truncated HIS3 allele. Both
      substrates are flanked by a HO endonuclease recognition site that can be targeted
      for incision by HO-endonuclease.  HO endonuclease recognition sites native to the
      MAT locus, on both copies of chromosome III, have been deleted in all strains. 
      This prevents interaction between the recombination substrates and other broken
      chromosome ends from interfering in the assay.  The KAN-MX-marked galactose
      inducible HO endonuclease expression cassette is inserted at the TRP1 locus on
      chromosome IV.  The substrates share 311 bp or 60 bp of the HIS3 coding sequence
      that can be used by the HR machinery for repair by SSA.  Cells that use these
      substrates to repair broken chromosomes by HR form an intact HIS3 allele and a
      tXV::III chromosomal translocation that can be selected for by the ability to
      grow on medium lacking histidine (Figure 2A). Translocation frequency by HR is
      calculated by dividing the number of histidine prototrophic colonies that arise
      on selective medium by the total number of viable cells that arise after plating
      appropriate dilutions onto non-selective medium (Figure 2B).  A variety of DNA
      repair mutants have been used to study the genetic control of translocation
      formation by SSA using this system(12-14).

PMID- 21968397
TI  - A disulfide-free single-domain V(L) intrabody with blocking activity towards
      huntingtin reveals a novel mode of epitope recognition.
AB  - We present the crystal structure and biophysical characterization of a human V(L)
      [variable domain immunoglobulin (Ig) light chain] single-domain intrabody that
      binds to the huntingtin (Htt) protein and has been engineered for antigen
      recognition in the absence of its intradomain disulfide bond, otherwise conserved
      in the Ig fold. Analytical ultracentrifugation demonstrated that the alphaHtt
      V(L) 12.3 domain is a stable monomer under physiological conditions even at
      concentrations >20 MUM. Using peptide SPOT arrays, we identified the minimal
      binding epitope to be EKLMKAFESLKSFQ, comprising the N-terminal residues 5-18 of
      Htt and including the first residue of the poly-Gln stretch. X-ray structural
      analysis of alphaHtt-V(L) both as apo protein and in the presence of the epitope
      peptide revealed several interesting insights: first, the role of mutations
      acquired during the combinatorial selection process of the alphaHtt-V(L) 12.3
      domain-initially starting from a single-chain Fv fragment-that are responsible
      for its stability as an individually soluble Ig domain, also lacking the
      disulfide bridge, and second, a previously unknown mode of antigen recognition,
      revealing a novel paratope. The Htt epitope peptide adopts a purely alpha-helical
      structure in the complex with alphaHtt-V(L) and is bound at the base of the
      complementarity-determining regions (CDRs) at the concave beta-sheet that
      normally gives rise to the interface between the V(L) domain and its paired V(H)
      (variable domain Ig heavy chain) domain, while only few interactions with CDR-L1
      and CDR-L3 are formed. Notably, this noncanonical mode of antigen binding may
      occur more widely in the area of in vitro selected antibody fragments, including
      other Ig-like scaffolds, possibly even if a V(H) domain is present.

PMID- 21968398
TI  - TRAF1/C5, eNOS, C1q, but not STAT4 and PTPN22 gene polymorphisms are associated
      with genetic susceptibility to systemic lupus erythematosus in Turkey.
AB  - A significant source of variability in the literature on systemic lupus
      erythematosus (SLE) susceptibility genes has been the inability to replicate
      genetic findings across different racial or ethnic groups. We investigated
      whether a single nucleotide polymorphism (SNP) of the STAT4 (rs7574865), PTPN22
      (rs2476601), TRAF1/C5 (rs10818488), and C1q (rs292001) genes as well as the 27-bp
      VNTR polymorphism on intron 4 of eNOS, previously associated with SLE in other
      populations, are also associated with SLE risk in Turkey. A group of 158 SLE
      patients and 155 healthy controls were included in this study. A genetic
      association of the TRAF1/C5, C1q, and eNOS gene polymorphism, but not of STAT4
      and PTPN22, was found to confer a degree of risk for SLE. These data highlight
      the importance of comparative studies in different populations to confirm the
      previously detected genetic associations.

PMID- 21968399
TI  - Laponite assisted dispersion of carbon nanotubes in water.
AB  - The ability of Laponite to stabilize aqueous suspensions of multiwalled carbon
      nanotubes (MWCNTs) was investigated with the help of analytical centrifugation,
      microscopic image analysis, and measurements of electrical conductivity of hybrid
      Laponite+MWCNT suspensions. The impact of nanotube concentration C(n) (0.0025-0.5
      wt%) and Laponite/MWCNTs ratio X (varied within 0-1 wt/wt) on the properties of
      Laponite+MWCNT hybrid suspensions was discussed. It was observed that sonication
      of MWCNTs at critical minimal concentration of Laponite X(c)~0.25+/-0.05 resulted
      in efficient dispersion and formation of stabilized suspensions of individual
      nanotubes. The stabilization of nanotubes in the presence of Laponite was
      explained by adsorption of Laponite particles and formation of a hydrophilic
      charged shell on the surface of nanotubes. Increase of MWCNT concentration above
      the critical value resulted in percolation and formation of spatially extended
      electrically conductive networks of particles.

PMID- 21968400
TI  - Synthesis of a beta-cyclodextrin-modified Ag film by the galvanic displacement on
      copper foil for SERS detection of PCBs.
AB  - A mono-6-thio-beta-cyclodextrin-modified silver film was synthesized via galvanic
      displacement on copper foil. The prepared silver films could enrich non-polar
      polychlorinated biphenyls (PCBs) molecules from hydrophilic phase using thiolate
      beta-cyclodextrins (SH-beta-CDs) as receptors. The components of as-prepared Ag
      coated-Cu (Ag-Cu) film were confirmed by powder X-ray diffraction (XRD). Both
      surface-enhanced Raman spectroscopy (SERS) and energy dispersive X-ray
      spectroscopy (EDS) measurements gave strong evidences that the thiolated beta
      cyclodextrins (SH-beta-CDs) had been immobilized on the surface of silver film.
      Compared to the substrates prepared in the absence of SH-beta-CD, the surface
      morphology of the CD-modified Ag films was obviously changed. The interfacial
      enrichment and the capability of substrates to form inclusion complexes with PCBs
      molecules were tested by using PCB-15 (4,4'-dichlorobiphenyl) as the probe
      molecules via SERS technique. The measured SERS spectra could distinguish the PCB
      15 molecules at micro-molar level according to the most intense CCC bending in
      plane mode of PCBs. The enhancement factor (EF) of the SERS substrates for PCB-15
      was 1.2*10(5), which was comparable with a number of previous reports.

PMID- 21968401
TI  - Adsorption of arsenite and selenite using an inorganic ion exchanger based on Fe
      Mn hydrous oxide.
AB  - The adsorption behaviour and mechanism of As(III) and Se(IV) oxyanion uptake
      using a mixed inorganic adsorbent were studied. The novel adsorbent, based on
      Fe(III)-Mn(III) hydrous oxides and manganese(II) carbonate, was synthesised using
      a hydrothermal precipitation approach in the presence of urea. The inorganic ion
      exchanger exhibited a high selectivity and adsorptive capacity towards As(III)
      (up to 47.6 mg/g) and Se(IV) (up to 29.0 mg/g), even at low equilibrium
      concentration. Although pH effects were typical for anionic species (i.e., the
      adsorption decreased upon pH increase), Se(IV) was more sensitive to pH changes
      than As(III). The rates of adsorption of both oxyanions were high. Fourier
      transform infrared (FTIR) and X-ray photoelectron spectroscopy (XPS) studies
      showed that the ion exchange adsorption of both anions took place via OH(-)
      groups, mainly from Fe(III) but also Mn(III) hydrous oxides. MnCO(3) did not
      contribute directly to As(III) and Se(IV) removal. A higher adsorptive capacity
      of the developed material towards As(III) was partly due to partial As(III)
      oxidation during adsorption.

PMID- 21968402
TI  - Pure short-chain glycerol fatty acid esters and glycerylic cyclocarbonic fatty
      acid esters as surface active and antimicrobial coagels protecting surfaces by
      promoting superhydrophilicity.
AB  - Pure glycerol fatty acid esters and glycerylic cyclocarbonic fatty acid esters
      have an amphiphilic structure, giving these biomolecules a broad range of physico
      chemical and biological properties. Physico-chemical properties depend on chain
      lengths, odd or even carbon numbers on the chain, and glyceryl or cyclocarbonic
      polar heads. The spectrum of melting-point values for these molecules is large.
      Surface-activity is very important and through determination of the critical
      aggregation concentration (CAC), some fatty-acid esters are considered as solvo
      surfactant biomolecules. Coupling these self-aggregation and crystallization
      properties, superhydrophilic surfaces were obtained. An efficient durable water
      repellent coating of various metallic and polymeric surfaces was allowed.
      Moreover, these fatty acid esters promoting superhydrophilicity showed biological
      activity against Gram positive, Gram negative, and yeast-like micro-organisms.
      Such surfaces coated by self-assembled fatty acid esters in a stable coagel state
      present a novel solution to surface-contamination risks from pathogen
      proliferation.

PMID- 21968403
TI  - Normalizing considerations for time to stabilization assessment.
AB  - OBJECTIVES: Because of the growing use of time to stabilization (TTS) and similar
      measures with single-limb landings in lower extremity research, it is important
      to determine if the task performance needs to be normalized further. The purpose
      of this study was to compare TTS of healthy participants using a standardized
      versus a normalized horizontal jumping distance. DESIGN: Crossover study.
      METHODS: Twenty-one healthy participants performed single landings using two
      horizontal jumping distances: standardized (70 cm) and normalized (leg length).
      Resultant vector TTS (RVTTS) was calculated to represent the dynamic stability
      performance. RESULTS: For RVTTS, the participants took significantly longer to
      stabilize when using the normalized jumping distance (1.997+/-0.181 s) compared
      with the standardized jumping distance (1.921+/-0.126 s) (t=5.134; p<0.001;
      power=0.65). RVTTS during the normalized jumping distance was more strongly
      correlated with leg length (r=0.628; p=0.002) than during the standardized
      jumping distance (r=0.563; p=0.008). CONCLUSIONS: Normalizing the horizontal
      jumping distance during the single-limb jumping task creates a performance
      decrement in RVTTS among healthy participants. Because dynamic stability measured
      with RVTTS when jumping a normalized distance is more strongly correlated with
      leg length than when jumping a standardized jumping distance, researchers using
      this task and analysis may want to consider using this additional normalizing
      step in future investigations.

PMID- 21968405
TI  - Rising emergency department attendances: don't reinvent the wheel.

PMID- 21968404
TI  - Drosophila Met and Gce are partially redundant in transducing juvenile hormone
      action.
AB  - The Drosophila Methoprene-tolerant (Met) and Germ cell-expressed (Gce) bHLH-PAS
      transcription factors are products of two paralogous genes. Both proteins
      potentially mediate the effect of juvenile hormone (JH) as candidate JH
      receptors. Here we report that Met and Gce are partially redundant in transducing
      JH action. Both Met and gce null single mutants are fully viable, but the Met gce
      double mutant, Met(27) gce(2.5k), dies during the larval-pupal transition.
      Precocious and enhanced caspase-dependent programmed cell death (PCD) appears in
      fat body cells of Met(27) gce(2.5k) during the early larval stages. Expression of
      Kr-h1, a JH response gene that inhibits 20-hydroxyecdysone (20E)-induced broad
      (br) expression, is abolished in Met(27) gce(2.5k) during larval molts.
      Consequently, expression of br occurs precociously in Met(27) gce(2.5k), which
      may cause precocious caspase-dependent PCD during the early larval stages.
      Defective phenotypes and gene expression changes in Met(27) gce(2.5k) double
      mutants are similar to those found in JH-deficient animals. Importantly,
      exogenous application of JH agonists rescued the JH-deficient animals but not the
      Met(27) gce(2.5k) mutants. Our data suggest a model in which Drosophila Met and
      Gce redundantly transduce JH action to prevent 20E-induced caspase-dependent PCD
      during larval molts by induction of Kr-h1 expression and inhibition of br
      expression.

PMID- 21968407
TI  - Jack of all trades, master of none.

PMID- 21968408
TI  - Prescribing for children.
AB  - Many children receive urgent care within emergency departments. Children are at
      increased risk from the use of medicines for a number of reasons, including the
      need to calculate a weight or age-based dose or administration of a fraction or
      proportion of an adult formulation of medicine. Aspects of good practice from the
      English National Service Framework (NSF) for Children, Young People and Maternity
      Services are highlighted. The importance of good medicines reconciliation is
      discussed. Websites that support emergency care practitioners to address
      medicines adherence and counselling of parents and children on use of medicines
      are presented. The drug related needs of children and young people must be
      assessed on an individual basis. Guidelines are outlined to support safe
      prescribing and medicines administration.

PMID- 21968409
TI  - For children leaving the emergency department before being seen by a physician,
      counseling from nurses decreases return visits.
AB  - BACKGROUND: Nurses counsel the parents of patients leaving without being seen by
      a physician (LWBS) about common childhood illnesses. This strategy's impact is
      not known. OBJECTIVE: To assess the impact of nurse counseling on ED return
      visits and outcomes for children who LWBS. METHODS: This retrospective cohort
      study used the computerized database of a tertiary care pediatric ED.
      Participants were all triaged children who LWBS between April 1st 2008 and March
      31st 2009. Parents who notified nurses of their intention to leave received
      information and counseling on when to return. This counseling's occurence was
      this study's exposure of interest. The control group included patients who LWBS
      without notification and thus were not counseled. The primary outcome was a
      return visit to the ED within 48h. Triage level and referral status were used as
      severity indicators. To demonstrate a 2% difference in return visits (alpha value
      0.05, power 80%), 3213 participants were needed per group. RESULTS: During the
      study period, 60,525 patients consulted the ED and 10,323 LWBS; of these, 4639
      (45%) received nurse counseling and 5684 (65%) did not. There was a 2.0% (95% CI
      1.0, 3.0) decrease in ED return visit proportions between groups. On multiple
      logistic regression, the counseled group was less likely to return to the ED
      within 48h. CONCLUSION: This study suggests that, of patients who LWBS, those who
      receive counseling by a nurse have less return visits in the following 48h.

PMID- 21968410
TI  - Reliability and validity of the modified preverbal, early verbal pediatric pain
      scale in emergency department pediatric patients.
AB  - INTRODUCTION: Research has demonstrated that children are at particular risk for
      oligoanalgesia due to assessment difficulties when they are unable to self
      report. We sought to evaluate the psychometric properties of the Modified
      Preverbal, Early Verbal Pediatric Pain Scale (M-PEPPS) when used in an emergency
      department pediatric population. METHODS: We conducted a secondary analysis of
      data from a prospective, observational study of pain in emergency patients to
      evaluate the M-PEPPS tool. Data from 118 pediatric patients was subjected to item
      analysis, reliability analysis, and common factor analysis. RESULTS: Item
      difficulties suggest that the items capture the range of pain states from mild to
      severe. Corrected item-total correlations indicate that the instrument
      discriminates between various levels of pain. Common factor analysis yielded a
      single, unrotated common factor solution providing evidence that the M-PEPPS
      measures the single construct of pain. Cronbach's alpha for the scale (0.954)
      suggests excellent reliability. CONCLUSIONS: Findings indicate that the M-PEPPS
      instrument is reliable when used by emergency nurses to measure pediatric pain.
      The single-factor common factor solution provides support for the scale as
      measuring the single construct of pain. Additional research is necessary to
      establish the degree of change in score required for a clinically meaningful
      reduction in pain to be present.

PMID- 21968411
TI  - Clinical pattern of pediatric ocular trauma in fast developing country.
AB  - BACKGROUND: Ocular trauma is a significant problem in pediatric patients. Also,
      leads to visual loss throughout the world there are no data of pediatric ocular
      trauma in Arabian Gulf Countries in the current literature. AIM: To study the
      epidemiology, mechanism, causes and outcome of serious ocular trauma requiring
      hospital admission, in children below 16years of age. STUDY DESIGN: A
      retrospective cohort study. SUBJECTS: All pediatric patients (up to 16years of
      age) presenting with ocular injuries to a tertiary care pediatric ophthalmology
      and Pediatric Accident Emergency Department 1 January 2005 to 30 December 2009.
      METHODS: Each file was studied to find out the demographic data, mechanism and
      cause of injury. The definitions and classifications of ocular trauma in our
      study were modified from the Ocular Trauma Classification Group guidelines and
      Birmingham Eye Trauma Terminology Presenting and final visual acuity were
      recorded along with details of anterior and posterior segment evaluation.
      RESULTS: Hundred and six files of the children admitted to ophthalmology ward
      with the diagnosis of ocular trauma between 2005 and 2009 were reviewed. Majority
      were boys (77.4%). The mean age at admission was 6.63years. A higher incidence of
      ocular trauma was noted in children above 5years than those below (58.5%). Most
      number of trauma occurred at home (42.5%, n=45) followed by street (35.8% n=34),
      school (12.3%, n=13), sporting area (5.7%, n=6). Also, eight patients (8.5%)
      involved in Road Traffic Accidents (RTA). Closed globe injury occurred more
      frequently than open globe injury (59.4% vs. 40.6%). Initial visual acuity was
      more than 6/60 in (55.6%) patients of closed globe while in open globe injury was
      (37.3%). Final visual acuity was more than 6/18 in (82.5%) patients of closed
      globe injury group and in (63%) patients of open globe injury group. Severe
      impairment of vision was found in (11.6%) and blindness (4.7%) only in open globe
      injury group. CONCLUSION: Most eye injuries in children are preventable so this
      reflects the importance of health education, adult supervision and application of
      appropriate measures that is necessary for reducing the incidence and severity of
      trauma.

PMID- 21968412
TI  - Children and young people's participation in healthcare consultations in the
      emergency department.
AB  - Approximately 4 million children attend emergency departments (ED) in England,
      United Kingdom, per annum. It is important for children and young people to have
      an active say in their assessment and treatment during each emergency care
      episode. However the reality of hearing the child or young person's voice within
      active participation in health care consultations remains low at approximately 6%
      of voices recorded. In the context of policy drivers and patient benefits, there
      is a need to increase the level of participation by children and young people
      within the emergency care environment. However, noise, child and parental anxiety
      and distress, professional time pressure, and severity of child illness or injury
      add to the inherent complexity of triadic communication (parent, child,
      healthcare professional) in the ED. Research examining child participation in
      decision-making in ED is sparse and guidance for all parties is limited.
      Therefore methods drawn from the wider literature on child participation are
      discussed which may be implemented, validated and evaluated with an ED context.

PMID- 21968413
TI  - Pediatric neurologic exam.
AB  - Although emergency nurses receive education and training in performing
      comprehensive and rapid assessment, pediatric patients may prove to be
      challenging due to dynamic growth, development and maturation. If the emergency
      department (ED) has limited exposure to pediatric patients, performing
      assessments and prompt interventions may be daunting. Neonates, infants and young
      children with illness or trauma have unique and often times subtle signs and
      symptoms that can change rapidly. Although the neurological exam for older
      children may be similar to that of an adult, there are significant differences
      based on maturation. The neurologic exam for neonates and infants provides the
      nurse with even more opportunity to be familiar with developmental differences.
      Therefore, it is important for ED nurses to become familiar with typical
      development and early recognition of neurologic insult.

PMID- 21968414
TI  - Golf club related basal skull fracture: a case study.
AB  - Basal skull fractures, although rare, do occur and a high index of suspicion for
      high velocity injuries, should be at the forefront of the clinicians mind,
      particularly those from a golf club. Head injury in children is a common
      presentation to any Paediatric Emergency Department. With effective examination
      skills, recognition of signs of basal skull fracture such as haemotympanum, even
      in the absence of altered neurological findings, ensures safe and effective
      practice enabling correct and justifiable clinical decisions to be made. This is
      vital to ensure not only the correct investigative procedure is requested and
      performed, but also on discussion with the appropriate specialists, the correct
      treatment is also prescribed. This case study examines the use of computed
      tomography in the diagnosis of basal skull fractures and highlights further
      discussion into the appropriate treatment of children diagnosed with basal skull
      fractures.

PMID- 21968415
TI  - Who should nurse children requiring emergency care?
AB  - There are constant challenges in developing a workforce fit to deliver care to
      children and young people requiring emergency or urgent care. These challenges
      are often compounded when the care setting for children and young people is
      within a general Emergency Department. This paper will review contemporary issues
      around who should deliver emergency care to children in these settings; reasoned
      debate is required to ensure that we have a workforce fit for purpose.

PMID- 21968416
TI  - Matrix metalloproteinase 2 promotes cell growth and invasion in colorectal
      cancer.
AB  - Colorectal cancer (CRC) is the third leading cause of cancer-related death in the
      western world. In this study, we evaluated the expression of matrix
      metalloproteinase 2 gene (MMP2) in CRC and analyzed its correlation with
      clinicopathological features. We found that the expression of MMP2 was
      significantly higher in CRC tissues than in the colorectal tissues. In addition,
      high levels of MMP2 protein were positively correlated with the status of tumor
      size, lymph node metastasis, distant metastasis, Dukes' stage, and tumor
      invasion. Moreover, patients with higher MMP2 levels had markedly shorter overall
      survivals than those with low MMP2 levels. Multivariate analysis results
      suggested that the level of MMP2 expression is an independent prognostic
      indicator for the survival of patients with CRC. Silencing MMP2 expression in CRC
      cell lines with lentiviral-mediated shRNA markedly suppressed cell proliferation,
      colony formation, and invasion. Furthermore, we observed that vascular
      endothelial growth factor (VEGF) and membrane type 1 (MT1)-MMP protein levels
      were decreased in MMP2-down-regulated colorectal cells. Therefore, our study
      demonstrated that MMP2 is an important factor related to carcinogenesis and
      metastasis of CRC, and MMP2 promotes CRC cell growth and invasion by up
      regulating VEGF and MT1-MMP expression, which makes this pathway a potential
      target for cancer treatment.

PMID- 21968417
TI  - Jugular vein hypoplasia can preclude extracorporeal membrane oxygenation
      cannulation in the neonate with congenital diaphragmatic hernia: potential
      identification of the neonate at risk by fetal magnetic resonance imaging.
AB  - Magnetic resonance imaging (MRI) is used routinely in many fetal care centers for
      the evaluation of the fetus with congenital diaphragmatic hernia (CDH). Current
      MRI strategies focus on identifying the type of hernia and its contents, as well
      as calculating fetal lung volumes, in order to plan appropriately for neonatal
      support, including the use of extracorporeal membrane oxygenation (ECMO). Single
      shot fast spin-echo T(2)-weighted sequences are fundamental, with additional
      sequences used variably as indicated. We report the case of a fetus with CDH in
      whom ECMO cannulation was attempted as a neonate but was unsuccessful because of
      variant anatomy of the internal jugular vein. A retrospective review of gradient
      echo sequences obtained through the fetal neck and chest showed the abnormality
      could have been anticipated. During multidisciplinary assessment of the fetus
      with CDH, consideration should be given to imaging evaluation of the neck to
      evaluate the cervical vascular anatomy, particularly in cases with poorer
      prognosis in whom it is anticipated that neonatal ECMO may be an option.

PMID- 21968418
TI  - Novel piperazine induces apoptosis in U937 cells.
AB  - The effect of 1,4-bis-(4-(1H-benzo[d]imidazol-2-yl-phenyl)) piperazine (BIPP), a
      newly synthesized piperazine derivative, on U937 leukemia cell viability was
      investigated. We show that BIPP induces dose-responsive apoptotic cell death in
      U937 cells by intrinsic mechanisms of apoptosis. Maximum apoptotic effect of BIPP
      on U937 cells was observed at 12.8MUM. BIPP-induced apoptosis was evident by
      characteristics such as altered annexin-V binding, caspase activation, loss of
      mitochondrial membrane potential (MMP) and cytochrome c release. BIPP also
      differentially activates initiator and effector caspases combined with the loss
      of MMP strongly suggesting that BIPP causes an intrinsic apoptosis in U937
      leukemia cells. Due to our observations that BIPP induces leukemia cell death
      without significantly affecting normal cells, our data suggests that it may be a
      potential therapeutic agent for human myeloid leukemia.

PMID- 21968419
TI  - c-Jun N-terminal kinase mediates microtubule-depolymerizing agent-induced
      microtubule depolymerization and G2/M arrest in MCF-7 breast cancer cells.
AB  - Microtubule-binding agents (MBAs) form one of the most important anticancer-drug
      families, but their molecular mechanisms are poorly understood. MBAs such as
      paclitaxel (PTX) stabilize microtubules, whereas XRP44X (a novel pyrazole) and
      combretastatins A4 (CA4) destabilize microtubules. These two different types of
      MBAs have potent antitumor activity. Comparisons of their effects on signal
      transduction and cellular responses will help uncover the molecular mechanism by
      which MBAs affect tumor cells. We used MCF-7 cells to compare the effects of the
      three MBAs on the cytoskeleton, cell cycle distribution, and activation of the
      three major mitogen-activated protein kinase (MAPK) signaling cascades
      [extracellular signal-related kinases, c-Jun N-terminal kinase (JNK), and p38
      MAPK] using pharmacological inhibitors. The G2/M phase arrest was induced
      following polymerization of microtubules by PTX and depolymerization by XRP44X
      and CA4. The three major MAPKs were rapidly activated by XRP44X, and
      extracellular signal-related kinases and p38 by PTX, whereas JNK did not quickly
      respond to PTX. Pharmacological inhibitors indicated that activation of JNK is
      principally required for XRP44X- and CA4-induced microtubule depolymerization and
      G2/M phase arrest. Our results suggest that early phosphorylation of JNK is a
      specific mechanism involved in microtubule depolymerization by certain MBAs.

PMID- 21968420
TI  - Digital EPR with an arbitrary waveform generator and direct detection at the
      carrier frequency.
AB  - A digital EPR spectrometer was constructed by replacing the traditional bridge
      with an arbitrary waveform generator (AWG) to produce excitation patterns and a
      high-speed digitizer for direct detection of the spin system response at the
      carrier frequency. Digital down-conversion produced baseband signals in
      quadrature with very precise orthogonality. Real-time resonator tuning was
      performed by monitoring the Fourier transforms of signals reflected from the
      resonator during frequency sweeps generated by the AWG. The capabilities of the
      system were demonstrated by rapid magnetic field scans at 256 MHz carrier
      frequency, and FID and spin echo experiments at 1 and 10 GHz carrier frequencies.
      For the rapid scan experiments the leakage through a cross-loop resonator was
      compensated by adjusting the amplitude and phase of a sinusoid at the carrier
      frequency that was generated with another AWG channel.

PMID- 21968421
TI  - Do European doctors support measles, mumps, rubella vaccination programmes
      enough?

PMID- 21968422
TI  - Tick-borne encephalitis increasing in Sweden, 2011.

PMID- 21968423
TI  - Tick-borne encephalitis in Europe, 2007 to 2009.

PMID- 21968424
TI  - Measles in Geneva between 2003 and 2010: persistence of measles outbreaks despite
      high immunisation coverage.

PMID- 21968425
TI  - Highlights from the clinical symposium on Shiga toxin-producing Escherichia coli
      / haemolytic uremic syndrome, Berlin, September 2011.

PMID- 21968428
TI  - Effects of nitric oxide synthase-3 overexpression on post-translational
      modifications and cell survival in HepG2 cells.
AB  - Hepatocarcinoma is the fifth most common neoplasm and the third cause of cancer
      related death. The development of genetic- and/or molecular-based therapies is
      urgently required. The administration of high doses of nitric oxide (NO) promotes
      cell death in hepatocytes. NO contributes to cell signaling by inducing
      oxidative/nitrosative-dependent post-translational modifications. The aim of the
      present study was to investigate protein modifications and its relation with
      alteration of cell proliferation and death in hepatoma cells. Increased
      intracellular NO production was achieved by stable nitric oxide synthase-3 (NOS
      3) overexpression in HepG2 cells. We assessed the pattern of nitration,
      nitrosylation and carbonylation of proteins by proteomic analysis. The results
      showed that NOS-3 cell overexpression increased oxidative stress, which affected
      proteins mainly involved in cell protein folding. Carbonylation also altered
      metabolism, as well as immune and antioxidant responses. The interaction of
      nitrosative and oxidative stress generated tyrosine nitration, which affected the
      tumor marker Serpin B3, ATP synthesis and cytoskeleton. All these effects were
      associated with a decrease in chaperone activity, a reduction in cell
      proliferation and an increased cell death. Our study showed that alteration of
      nitration, nitrosylation and carbonylation pattern of proteins by NO-dependent
      oxidative/nitrosative stress was related to a reduction of cell survival in a
      hepatoma cell line.

PMID- 21968427
TI  - The ups and downs of DNA repair biomarkers for PARP inhibitor therapies.
AB  - PARP inhibitors are emerging as a valuable new drug class in the treatment of
      cancer. Recent discoveries make a compelling case for the complexity of DNA
      repair biomarker evaluation and underscore the need to examine at multiple
      biomarkers in a relational manner. This review updates the current trends in DNA
      repair biomarker strategies in use for the PARP inhibitors and describes the
      impact of many DNA repair biomarkers on PARP inhibitor benefit in the cancer
      clinic.

PMID- 21968429
TI  - Proteomic analysis of a rat pancreatic stellate cell line using liquid
      chromatography tandem mass spectrometry (LC-MS/MS).
AB  - Pancreatic stellate cells (PaSC) are emerging as key mediators in chronic
      pancreatitis and pancreatic cancer pathogenesis. Proteins regulating the
      biomolecular pathways involved in the conversion of quiescent to activated PaSC
      may have a significant influence on the development of chronic pancreatitis. We
      aim to compare differentially expressed proteins in activated and serum-starved
      non-proliferating PaSC using a mass spectrometry-based proteomics strategy. We
      cultured an immortalized rat PaSC cell line in media supplemented with 10% fetal
      bovine serum and in serum-free media. Using gel-based mass spectrometry (GeLC
      MS/MS), we identified nearly 1500 proteins. Qualitative and quantitative
      proteomic analysis revealed several hundred proteins as differentially abundant
      between the two cell states. Proteins of greater abundance in activated PaSC
      included isoforms of actin (e.g., smooth muscle actin) and ribosomal proteins.
      Conversely, proteins more abundant in non-proliferating PaSC than in activated
      PaSC included signaling proteins MAP kinase 3 and Ras-related proteins. In
      addition, we have determined the molecular functions and biological pathways for
      these proteins. We are confident that the application of mass spectrometry-based
      strategies, such as that described herein, to investigate specific proteins in
      PaSC may lead to a better understanding of the molecular mechanisms involved in
      pancreatic diseases, such as chronic pancreatitis.

PMID- 21968430
TI  - Validation of the harmless acute pancreatitis score in predicting nonsevere
      course of acute pancreatitis.
AB  - BACKGROUND: The Harmless Acute Pancreatitis Score (HAPS) is a scoring algorithm
      to identify patients with nonsevere acute pancreatitis. The aim of this study was
      to evaluate the reproducibility of HAPS outside its original study setting.
      METHOD: Baseline information of all hospitalized patients with acute pancreatitis
      at Karolinska University Hospital, Stockholm, Sweden, between 2004 and 2009 was
      collected. The parameters constituting HAPS were signs of peritonitis, hematocrit
      and serum creatinine levels. Since hematocrit was not available in all patients,
      complete sample analysis was performed by replacing hematocrit with hemoglobin
      (strongly correlated with hematocrit; r = 0.86). RESULTS: In total, 531 patients
      with a first-time or a recurrent attack of acute pancreatitis were included.
      Among 353 patients with complete information on parameters constituting HAPS, 79
      patients were predicted to have a nonsevere course, of whom 1 patient developed
      severe acute pancreatitis. The specificity of HAPS in predicting a nonsevere
      course of acute pancreatitis was 96.3% (95% CI: 81.0-99.9) with a corresponding
      positive predictive value of 98.7% (95% CI: 93.1-100). Complete sample analysis
      replacing hematocrit with hemoglobin level predicted a nonsevere course in 182
      patients, of whom 2 patients had severe acute pancreatitis (94.3% specificity and
      98.9% positive predictive value). CONCLUSION: HAPS is a highly specific scoring
      algorithm that predicts a nonsevere course of acute pancreatitis. Therefore, HAPS
      might be an additional tool in the clinical assessment of acute pancreatitis
      where early screening is important to treat the patients at an optimal level of
      care.

PMID- 21968432
TI  - [131I]Metaiodobenzylguanidine therapy in neural crest tumors: varying outcome in
      different histopathologies.
AB  - AIM: To evaluate the response of [131I] metaiodobenzylguanidine ([131I]MIBG)
      therapy in patients with neuroectodermal tumors and to assess their quality of
      life using the functional assessment of cancer therapy - general quality-of-life
      questionnaire for patients who are on follow-up after MIBG therapy. MATERIALS AND
      METHODS: Thirty-two patients diagnosed with various subtypes of neuroectodermal
      tumors and treated with [131I]MIBG were included in this retrospective analysis.
      Response to therapy was evaluated objectively by comparing pretherapy and
      posttherapy biochemical markers, radiological investigations, and follow-up MIBG
      scans. Symptomatic response and quality of life were also evaluated in the follow
      up visits. RESULTS: In seven patients with stage III neuroblastoma, an objective
      response rate was seen in 57% and a symptomatic response rate was seen in 29% of
      the patients. Among 11 patients with stage IV neuroblastoma, an objective
      response was observed in 36% and a symptomatic response in 36% of the patients.
      Among 12 patients with pheochomocytoma and paraganglioma, an objective response
      was noticed in 8%, but symptomatic improvement and stabilization of disease were
      seen in 75% of the patients belonging to this category. One patient with
      medullary carcinoma of the thyroid and one patient with mediastinal carcinoid did
      not show an objective response but had a stable disease; both patients showed
      symptomatic improvement. Quality of life has improved in all 11 patients who are
      still on follow-up. CONCLUSION: [131I]MIBG therapy can be of significant value in
      the treatment of patients with chemotherapy-resistant stage III and IV
      neuroblastomas who demonstrate good tracer uptake in diagnostic scans. MIBG
      therapy has the potential to stabilize the disease and provide symptomatic
      improvement in patients with metastatic/recurrent pheochomocytoma/paraganglioma
      and medullary carcinoma thyroid and carcinoid in which there is evidence of
      tracer accumulation in the tumor. Both single high dose or multiple fractionated
      doses are equally effective in improving the quality of life in
      metastatic/recurrent pheochomocytoma/paraganglioma.

PMID- 21968431
TI  - A preliminary report on the impact of 18F-FDG PET/CT in the management of
      paediatric head and neck cancer.
AB  - INTRODUCTION: Paediatric head and neck malignancy accounts for 5% of all
      paediatric cancers. The choice of treatment and prediction of prognosis depend on
      the histological type of tumour, initial staging, evaluating treatment response
      and detection of early recurrence. Conventional imaging modalities have many
      limitations. Positron emission tomography/computed tomography (PET/CT) is more
      accurate; however, so far, the literature lacks reports of large groups of
      paediatric patients. AIM: To report the role of PET/CT in factors affecting the
      choice of treatment at the newly established Children Cancer Hospital in Cairo,
      Egypt, which is one of the busiest dedicated paediatric oncology centres in the
      world. All findings were proven by histopathology, radiology and by clinical
      follow-up. PATIENT POPULATION: Thirty-six paediatric patients (30 boys and six
      girls) with various histologically proven head and neck cancers were included in
      this study. Their age ranged from 2 to 17 years. High-resolution diagnostic CT
      and/or MRI of the head and neck, and in relevant cases also of the chest and the
      abdomen, were performed in all patients at a mean interval of 1.6 weeks (range, 1
      3 months) before the PET/CT study. Results of PET/CT were compared with the
      findings of these conventional imaging modalities. RESULTS: The sensitivity,
      specificity, accuracy, positive and negative predictive values of PET/CT against
      the conventional imaging were as follows: sensitivity 100 and, 53%, specificity
      89.5 and 47%, accuracy 94.5 and 50%, positive predictive value 89.5 and 47% and
      negative predictive value 100 and 53% respectively. PET/CT changed patient
      management in 50% of the cases. CONCLUSION: PET/CT in paediatric head and neck
      carcinoma is more accurate than conventional imaging. Therefore, it also has a
      significant impact on further patient management. We recommend that it should be
      the first imaging modality for all purposes in initial staging, evaluating
      treatment response and follow-up in paediatric head and neck carcinoma.

PMID- 21968433
TI  - Sentinel lymph node biopsy with a gamma probe in patients with high-risk
      cutaneous squamous cell carcinoma:  follow-up results of sentinel lymph node
      negative patients.
AB  - OBJECTIVE: Lymphoscintigraphy (LS) and sentinel lymph node biopsy have become the
      standard of care for melanoma and breast cancer. However, the data on patients
      with cutaneous squamous cell carcinoma (SCC) are limited. We aimed to evaluate
      and identify the role of LS and sentinel lymph node biopsy in patients with high
      risk cutaneous SCC. METHODS: Nineteen patients (13 men, six women; 47-87 years of
      age, mean age 67.5 +/- 12.3) with SCC were included in the study. LS was
      performed on all patients after intracutaneous injection of Tc-99m nanocolloid.
      Primary lesions and sentinel lymph nodes (SLNs) were excised with the help of a
      gamma probe. RESULTS: A total of 26 SLNs and 32 secondary lymph nodes were imaged
      on LS and were marked. During surgery, 29 SLNs, 21 secondary lymph nodes and
      three nonactive lymph nodes were excised. In total, 53 lymph nodes were removed
      surgically. A histopathological study revealed that all lymph nodes were negative
      for metastasis. Patients were followed up for an average of 41.1 +/- 22.2 months
      (7-80 months). Until the time of data collection, 14 patients were alive and had
      no regional lymph node or distant metastasis. Local recurrence was seen in only
      one patient. He was reoperated upon 38 months ago. CONCLUSION: The feasibility of
      determining SLNs using LS and an intraoperative gamma probe in patients with
      cutaneous SCC was shown. Unnecessary elective lymph node dissection and possible
      complications could be avoided in 19 patients.

PMID- 21968434
TI  - Determination of the optimal acquisition protocol of breath-hold PET/CT for the
      diagnosis of thoracic lesions.
AB  - OBJECTIVE: The aim of this study was to determine the optimal acquisition scan
      protocol for deep inspiration breath-hold (BH) fluoro-2-deoxy-D-glucose positron
      emission tomography (PET) for the examination of thoracic lesions. METHODS: We
      studied 32 thoracic lesions in 21 patients. Whole-body PET/computed tomography
      (CT) scanning with free breathing (FB) was performed for 3 min per bed position,
      followed by a BH-CT and five BH-PET for 20 s each. Summed BH images with total
      acquisition times of 40, 60, 80 and 100 s were generated (BH * 2, BH * 3, BH * 4
      and BH * 5, respectively). The displacements between PET and CT images, the
      lesion volume of the PET image, the maximum standardized uptake value (SUVmax)
      and the quality of the PET image were assessed in relation to the clinical
      characteristics of each patient and the summation of the BH-PET images. RESULTS:
      BH-PET decreased the tumor volume significantly (FB: 7.23 +/- 9.70 cm3, BH * 5:
      4.71 +/- 5.14 cm3, P<0.01) and increased the SUVmax (FB: 6.27 +/- 5.41, BH * 5:
      7.53 +/- 6.28, P<0.01). The displacement between the PET and CT images was
      improved significantly in the BH scans (FB: 0.77 +/- 0.53 cm, BH * 5: 0.36 +/-
      0.24 cm, P<0.01). In addition, aging and lung function of patients influenced the
      reproducibility of BH-PET. The summed BH-PET images, obtained by summation of
      three or more BH-PET images (total acquisition time of 60 s or more), achieved
      good image quality. CONCLUSION: BH-PET/CT improved the misregistration between
      PET and CT images and increased the SUVmax of thoracic lesions. The recommended
      number of BH-PET images for summation with 20 s of acquisition time is three or
      more.

PMID- 21968435
TI  - Preliminary biological evaluation of 125I-labeled anti-carbonic anhydrase IX
      monoclonal antibody in the mice bearing HT-29 tumors.
AB  - OBJECTIVE: To evaluate 125I-labeled anti-carbonic anhydrase IX monoclonal
      antibody (125I-MAb) as a novel single-photon emission computed tomography tracer
      for imaging carbonic anhydrase IX in the mice bearing HT-29 tumors. METHODS: Anti
      carbonic anhydrase IX monoclonal antibody was labeled with iodine-125 by the
      iodogen method. The radiochemical purity of 125I-MAb was measured by radio-thin
      layer chromatography. The in-vitro stability of 125I-MAb was determined in PBS
      (0.05 mol/l, pH 7.4) or new-born calf serum at 37 degrees C, and analyzed by
      radio-thin-layer chromatography. A biodistribution study and planar imaging were
      carried out in the mice bearing HT-29 tumors. The expression of CA IX in HT-29
      tumors was analyzed by immunohistochemistry. RESULTS: 125I-MAb was obtained with
      a radiolabeling efficiency of 98%, and showed high stability in PBS and new-born
      calf serum. Furthermore, the biodistribution study showed specific tumor uptake
      in the mice bearing HT-29 tumors, and planar imaging with 125I-MAb 48 h post
      injection showed a high concentration of radioactivity in tumors and a much
      decreased concentration in tumors in the blocking group. An immunohistochemical
      analysis showed the expression of CA IX in HT-29 tumors. CONCLUSION: The
      preliminary biodistribution study and results from planar imaging showed the
      potential of 125I-MAb as an agent for tumor diagnosis and encouraged further
      investigation.

PMID- 21968436
TI  - Predictors of residual cardiovascular risk in patients on statin therapy for
      primary prevention.
AB  - BACKGROUND: Low-density lipoprotein cholesterol-lowering therapy is an important
      aspect of primary prevention of cardiovascular disease (CVD). Statins are the
      most widely used drug therapy for achieving low-density lipoprotein goals based
      on an individual's 10-year risk. However, substantial risk of CVD events still
      exists even when a person is on statins. We sought to explore the predictors of
      future CVD events in individuals on statins with no pre-existing CVD. METHODS:
      The analysis was done on subjects who were on statins (n = 919) at baseline in
      the Multi-Ethnic Study of Atherosclerosis limited access dataset from the
      National Heart, Lung and Blood Institute. The primary outcome variable was all
      cause CVD events (n = 67). Multivariate regression Cox proportional hazard
      analysis was done to identify potential independent predictors of all-cause CVD.
      RESULTS: Our cohort consisted of 47% males, with a mean age of 66 +/- 9 years.
      Sixty-seven participants (7.3%) experienced CVD events during a mean follow-up of
      4.4 years. A higher coronary artery calcium score, homocysteine levels, waist
      circumference and a lower large arterial elasticity index were identified as
      independent predictors of CVD events. CONCLUSION: Homocysteine, waist
      circumference, coronary artery calcification and the large artery elasticity
      index appear to be the major independent predictors of CVD events in individuals
      on statins with no pre-existing CVD. In addition to emphasizing weight loss,
      alternative approaches beyond lipid reduction may need to be explored to better
      characterize and attenuate the residual risk in subjects on statin therapy for
      primary prevention.

PMID- 21968437
TI  - Identification of the two glycosyltransferase genes responsible for the
      difference between Escherichia coli O107 and O117 O-antigens.
AB  - The O-antigen is one of the most variable Gram-negative cell constituents, and
      its specificity is important for bacterial niche adaptation. The observed
      diversity of O-antigen forms is mainly due to genetic variations in O-antigen
      gene clusters. Less common is a change of gene function due to nucleotide
      substitution; a new instance of which is reported here. The O-antigens of E. coli
      O107 and O117 have similar structures differing only in a single sugar residue
      (GlcNAc in O107 substituted for Glc in O117). These O-antigen gene clusters
      contain the same set of 11 genes and share 98.6% overall DNA identity. The
      function of the genes in the gene clusters have been proposed previously, and a
      glycosyltransferase gene (wclY) with nucleotide polymorphism in each strain was
      proposed to transfer different sugars in different strains. To identify the gene
      responsible for the transfer of different sugars, wclY mutants of E. coli O107
      and O117 were constructed, and each mutant was complemented with the wclY genes
      cloned from both O107 and O117. Structural analysis of the O-antigens of the four
      recombinant strains identified wclY as a Glc-transferase in O117 and a GlcNAc
      transferase in O107. The evolutionary relationship of E. coli O107 and O117 O
      antigens is also discussed.

PMID- 21968438
TI  - Evidence for ethnic differences in cancer drug metabolism and deposition:
      potential relevance for clinical trials and practice.

PMID- 21968439
TI  - A simple guide screw method for intracranial xenograft studies in mice.
AB  - The grafting of human tumor cells into the brain of immunosuppressed mice is an
      established method for the study of brain cancers including glioblastoma (glioma)
      and medulloblastoma.  The widely used stereotactic approach only allows for the
      injection of a single animal at a time, is labor intensive and requires highly
      specialized equipment.  The guide screw method, initially developed by Lal et
      al.,(1) was developed to eliminate cumbersome stereotactic procedures. We now
      describe a modified guide screw approach that is rapid and exceptionally safe;
      both of which are critical ethical considerations.  Notably, our procedure now
      incorporates an infusion pump that allows up to 10 animals to be simultaneously
      injected with tumor cells. To demonstrate the utility of this procedure, we
      established human U87MG glioma cells as intracranial xenografts in mice, which
      were then treated with AMG102; a fully human antibody directed to HGF/scatter
      factor currently undergoing clinical evaluation(2-5).  Systemic injection of
      AMG102 significantly prolonged the survival of all mice with intracranial U87MG
      xenografts and resulted in a number of complete cures.  This study demonstrates
      that the guide screw method is an inexpensive, highly reproducible approach for
      establishing intracranial xenografts.  Furthermore, it provides a relevant
      physiological model for validating novel therapeutic strategies for the treatment
      of brain cancers.

PMID- 21968440
TI  - E-cadherin plasticity in prostate cancer stem cell invasion.
AB  - Prostate cancer that has progressed to metastatic disease remains largely
      untreatable. Nearly 90% of patients with advanced prostate cancer develop
      skeletal metastases, resulting in a substantial reduction in the quality of life
      and a drastic worsening of patient prognosis. The mechanisms involved in prostate
      cancer cell dissemination, however, remain poorly understood. We previously
      reported the identification of a highly tumorigenic E-cadherin positive prostate
      tumor stem cell subpopulation that expressed the embryonic stem cell markers SOX2
      and OCT3/4. We herein demonstrate that this subpopulation is also highly invasive
      and, importantly, is capable of altering its E-cadherin expression during the
      process of invasion. The non-tumorigenic E-cadherin negative subpopulation which
      minimally expresses SOX2 or OCT3/4 was found to be poorly invasive. In addition,
      targeted knockdown of SOX2 or OCT3/4 markedly suppressed the invasion of prostate
      cancer cells. Taken together, these findings indicate that the expression of SOX2
      or OCT3/4 is required for invasive cell capacity, but the ability to modulate E
      cadherin is the key permissive factor enabling cancer stem cell invasion in
      vitro. We therefore propose a model in which the post-epithelial to mesenchymal
      transition phenotype progresses to a frank, aggressive, and invasive phenotype by
      a process requiring the acquisition of E-cadherin plasticity. Considering the
      clinical significance of the metastatic complications of prostate adenocarcinoma,
      the identification of factors that promote the dissemination of the malignant
      prostate phenotype is essential to establish effective therapies to combat this
      disease in future.

PMID- 21968441
TI  - Stochastic resonance and coherence resonance in groundwater-dependent plant
      ecosystems.
AB  - Several studies have shown that non-linear deterministic dynamical systems forced
      by external random components can give rise to unexpectedly regular temporal
      behaviors. Stochastic resonance and coherence resonance, the two best known
      processes of this type, have been studied in a number of physical and chemical
      systems. Here, we explore their possible occurrence in the dynamics of
      groundwater-dependent plant ecosystems. To this end, we develop two eco
      hydrological models, which allow us to demonstrate that stochastic and coherence
      resonance may emerge in the dynamics of phreatophyte vegetation, depending on
      their deterministic properties and the intensity of external stochastic drivers.

PMID- 21968442
TI  - A mathematical representation of the development of Mycobacterium tuberculosis
      active, latent and dormant stages.
AB  - The majority of individuals infected with Mycobacterium tuberculosis (Mtb)
      bacilli develop latent infection. Mtb becomes dormant and phenotypically drug
      resistant when it encounters multiple stresses within the host, and expresses a
      set of genes, known as the dormancy regulon, in vivo. These genes are expressed
      in vitro in response to nitric oxide (NO), hypoxia (oxygen deprivation), and
      nutrient starvation. The occurrence and reactivation of latent tuberculosis (TB)
      is not clearly understood. The ability of the pathogen to enter and exit from
      different states is associated with its ability to cause persistent infection.
      During infection it is not known whether the organism is in a persistent slow
      replicating state or a dormant non-replicating state, with the latter ultimately
      causing a latent infection with the potential to reactivate to active disease. We
      collected gene expression data for Mtb bacilli under different stress conditions
      that simulate latency or dormancy. Time course experiments were selected and
      differentially expressed gene profiles were determined at each time point. A
      mathematical model was then developed to show the dynamics of Mtb latency based
      on the profile of differentially expressed genes. Analysis of the time course
      data show the dynamics of latency occurrence in vitro and the mathematical model
      reveals all possible scenarios of Mtb latency development with respect to the
      different conditions that may be produced by the immune response in vivo. The
      mathematical model provides a biological explanation of how Mtb latency occurs
      based on observed gene expression changes in in vitro latency models.

PMID- 21968443
TI  - The effects of motor learning on clinical isokinetic performance of
      postmenopausal women.
AB  - OBJECTIVE: To analyze the effects of motor learning on knee extension-flexion
      isokinetic performance during clinical isokinetic evaluation of postmenopausal
      women. METHODS: One-hundred and twenty postmenopausal women (60.3+/-3.2 years;
      BMI=27.6+/-4.7 kg/m(2)) without knee pain or injury and that never underwent
      isokinetic testing, were submitted to two bilateral knee extension-flexion
      (concentric-concentric) isokinetic evaluation (5 repetitions) at 60 degrees /s
      (BiodexTM Multi-Joint System 3 dynamometer). The tests were first performed in
      the dominant leg, with a 1-min recovery between them, and after a standardized
      warm-up that included 3 submaximal isokinetic repetitions. The same procedure was
      repeated in the non-dominant leg. Peak torque (PTQ) was adjusted for body weight
      (PTQ/BW), total work (TW), coefficient of variation (CV) and agonist/antagonist
      (agon/antag) ratio was compared between tests. RESULTS: Subjects showed greater
      levels (P<0.001) of PTQ, PTQ/BW and TW, and lower CV levels (P<0.01) in test 2 of
      both legs. Agon/antag ratio did not change significantly between tests.
      CONCLUSIONS: PTQ, PTQ/BW, TW and CV improved in the second knee extension flexion
      isokinetic testing of postmenopausal women. The results suggests that performing
      two tests, even with a short period of recovery between them, could be considered
      for reducing motor learning effects on clinical isokinetic evaluation of knee
      joint in postmenopausal women.

PMID- 21968444
TI  - A systematic review of intradermal influenza vaccines.
AB  - Influenza infection is associated with many complications, which can lead to
      hospitalizations and death. This is particularly true for the older adults who
      are not able to mount as good an immune response as younger adults due to their
      declining immune function. As such, different strategies are being evaluated to
      increase immunogenicity in the older adults, including use of adjuvanted vaccines
      and different delivery techniques, which can enhance immunogenicity as well as
      potentially be dose-sparing. The objective of this paper was to conduct a
      systematic review of studies that evaluated the efficacy (in terms of
      immunogenicity) and safety of intradermal (ID) influenza vaccines compared with
      traditional methods of administration in the general population and the older
      adults. Thirteen randomized, controlled, open-label trials were included in this
      systematic review. Seven trials were conducted in young adults 18-60 years of
      age, 4 trials were studied in older subjects >60 years, and 2 trials included
      both young and older adults, of which one did separate analyses for both groups
      and one did a separate analysis for the older adult population only. We found 7
      studies out of 8 for the 18-60-year olds and 4 out of 6 studies in the over 60
      year olds showed comparable efficacy between ID and intramuscular (IM)
      administration. Two out of 6 studies in the over 60-year olds showed superiority
      of ID administration over IM. Rates of adverse events occurring in the first 3
      days were comparable between ID and IM administration of influenza vaccines;
      however, when assessing adverse events occurring in the first 7 days, rates of
      local adverse events were consistently higher in the ID group, specifically
      erythema, swelling, induration, and pruritis. In conclusion, our review shows
      comparable efficacy between ID and IM administration of influenza vaccine in both
      the younger and older adults.

PMID- 21968445
TI  - A phase III randomized, controlled study to assess and compare the immunogenicity
      and tolerability of single and multi-dose vials of DTwP-Hib, a fully liquid
      quadravalent vaccine and their comparison with TETRAct-Hib vaccine in Indian
      infants aged 6-14 weeks.
AB  - Both WHO and IAP encourage using combination vaccines, wherever feasible. The
      phase III trial reported here was conducted to assess and compare the
      immunogenicity, tolerability and safety of two quadravalent vaccines,
      Quadrovax((r)) (new vaccine), and TETRAct-Hib((r)) (available in the market) in a
      multicentre study, in India. In all, 361 infants aged 6-8 weeks were enrolled,
      out of which 339 completed the study. The vaccination was done at 6-10-14 weeks
      following EPI/WHO recommended immunization schedule. Blood samples were collected
      prior to the administration of first dose and one month after the third dose.
      Postvaccination, geometric mean titres for each component did not differ
      significantly between the single dose vial and multi dose vial subgroups and
      among the two study groups. Adverse events observed were within the range quoted
      in literature. Quadrovax((r)) vaccine manufactured by SIIL was found to be safe,
      immunogenic and non-inferior to the comparator vaccine. The quadravalent vaccine
      is best recommended in the second year of life when children receive their
      booster dose at 15-18 months. It can be given to infants during primary
      immunization series at 6, 10 and 14 weeks of age when Hepatitis B vaccine is
      given in a separate arm or to infants at 10 weeks who receive the Hepatitis B
      vaccine separately following the 0, 6 and 14 weeks or 0, 1 and 6 months schedule.

PMID- 21968446
TI  - Characterization of the interactions of the pneumolysoid, Delta6 PLY, with human
      neutrophils in vitro.
AB  - The pneumolysin toxoid, Delta6 PLY, is a prototype pneumococcal protein vaccine
      candidate. However, its potentially detrimental residual pro-inflammatory
      interactions with human neutrophils are unknown. In the current study the effects
      of the toxoid (8-1000 ng/ml) have been compared with those of wild-type
      pneumolysin (WT/PLY, 8 ng/ml) on neutrophil cytosolic Ca(2+) fluxes, generation
      of leukotriene B(4) (LTB(4)), and release of matrix metalloproteinase-9 (MMP-9),
      using spectrofluorimetric, and ELISA procedures (LTB(4) and MMP-9) respectively.
      Exposure of neutrophils to WT/PLY resulted in influx of Ca(2+) and significant
      (P<0.05) release of MMP-9 and generation of LTB(4). However, treatment of the
      cells with Delta6 PLY at concentrations of up to 1000 ng/ml had only trivial
      effects on Ca(2+) influx and no effects on either release of MMP-9 or LTB(4)
      production. The observed absence of pro-inflammatory interactions of Delta6 PLY
      with neutrophils is clearly an important property of this pneumococcal protein
      vaccine candidate.

PMID- 21968448
TI  - A standardized classification of hypospadias.
AB  - OBJECTIVE: Systems for categorizing hypospadias are based on the location of the
      external meatus. The presented proposal draws on the organogenesis of the urethra
      and its position against the bone structure of the pelvis. The aim of the study
      was to examine the position of the corpus spongiosum division relative to pelvic
      bone structures as an indicator of the true level of hypospadias. PATIENTS AND
      METHODS: The study involved 150 patients aged 6 months to 22.8 years admitted for
      primary repair. The division of the corpus spongiosum was examined relative to
      the shaft of the penis and the upper pubis. Hypospadias above the pubis was
      categorized as penile, while below was proximal, with further subcategorization.
      The quality of the distal urethral canal was assessed. RESULTS: The external
      meatus was above the pubis in 94.1% while the division of corpus spongiosum was
      located above the pubis in 90% (distal penile 38%, mid shaft 25.3%). There was a
      considerable difference in hypospadias level relative to the indicator used. The
      distal meatus/urethra was stenotic in 84%, hypoplastic in 86.8% with true chordee
      in 10.4%. CONCLUSIONS: A classification of hypospadias based on organogenesis and
      in respect to bony structures of the pelvis seems reliable, consistent, and more
      surgically oriented. The distal urethral canal should be regarded as a fistula.

PMID- 21968447
TI  - Evaluation of DNA encoding acidic ribosomal protein P2 of Cryptosporidium parvum
      as a potential vaccine candidate for cryptosporidiosis.
AB  - The Cryptosporidium parvum acidic ribosomal protein P2 (CpP2) is an important
      immunodominant marker in C. parvum infection. In this study, the CpP2 antigen was
      evaluated as a vaccine candidate using a DNA vaccine model in adult C57BL/6 IL-12
      knockout (KO) mice, which are susceptible to C. parvum infection. Our data show
      that subcutaneous immunization in the ear with DNA encoding CpP2 (CpP2-DNA)
      cloned into the pUMVC4b vector induced a significant anti-CpP2 IgG antibody
      response that was predominantly of the IgG1 isotype. Compared to control KO mice
      immunized with plasmid alone, CpP2-immunized mice demonstrated specific in vitro
      spleen cell proliferation as well as enhanced IFN-gamma production to recombinant
      CpP2. Further, parasite loads in CpP2 DNA-immunized mice were compared to control
      mice challenged with C. parvum oocysts. Although a trend in reduction of
      infection was observed in the CpP2 DNA-immunized mice, differences between groups
      were not statistically significant. These results suggest that a DNA vaccine
      encoding the C. parvum P2 antigen is able to provide an effective means of
      eliciting humoral and cellular responses and has the potential to generate
      protective immunity against C. parvum infection but may require using alternative
      vectors or adjuvant to generate a more potent and balanced response.

PMID- 21968452
TI  - Contribution of interleukin-1 receptor accessory protein B to interleukin-1
      actions in neuronal cells.
AB  - Interleukin (IL)-1 is an important neuroimmunomodulator and a key mediator of
      inflammation during brain disorders. It acts on neuronal and glial cells via
      binding to the IL-1 type 1 receptor and IL-1 receptor accessory protein (IL
      1RAcP). More recently, a neuronal-specific isoform of IL-1RAcP, named IL-1RAcPb,
      has been identified. Our aim was to determine the role of IL-1RAcPb in IL-1
      actions in neuronal and glial cells, and to further explore the signaling
      mechanisms of IL-1 in neurons. We found that IL-1RAcPb deletion had no effect on
      IL-1alpha- and IL-1beta-induced activation of the extracellular signal-regulated
      kinase 1/2 or IL-6 release in glial cultures, although IL-6 release in response
      to high IL-1alpha concentration (30 IU/ml) was significantly reduced. We
      identified the p38 kinase as a key signaling element in IL-1alpha- and IL-1beta
      induced IL-6 synthesis and release in neuronal cultures. IL-1RAcPb deletion had
      no effect on IL-1alpha- and IL-1beta-induced IL-6 release in neurons, but
      significantly reduced IL-1alpha- but not IL-1beta-induced p38 phosphorylation.
      Our data demonstrate that the p38 signaling pathway plays an important role in IL
      1 actions in neurons, and that IL-1RAcP may regulate some, but not all, neuronal
      activities in response to IL-1alpha.

PMID- 21968453
TI  - Reliable protein production in a Pseudomonas fluorescens expression system.
AB  - A bottleneck to product development can be reliable expression of active target
      protein. A wide array of recombinant proteins in development, including an ever
      growing number of non-natural proteins, is being expressed in a variety of
      expression systems. A Pseudomonas fluorescens expression platform has been
      developed specifically for recombinant protein production. The development of an
      integrated molecular toolbox of expression elements and host strains, along with
      automation of strain screening is described. Examples of strain screening and
      scale-up experiments show rapid development of expression strains producing a
      wide variety of proteins in a soluble active form.

PMID- 21968454
TI  - Core-shell Ag@SiO2@mSiO2 mesoporous nanocarriers for metal-enhanced fluorescence.
AB  - A novel mesoporous nanocarrier consisting of a silver core, a silica spacer with
      controlled thickness and a fluorophores-loaded mesoporous silica shell was
      fabricated for the metal-enhanced fluorescence (MEF) and Forster resonance energy
      transfer (FRET) effects.

PMID- 21968457
TI  - Treating anxiety in patients with coronary heart disease: a randomized controlled
      trial.
AB  - BACKGROUND: Anxiety is frequent in patients with coronary heart disease (CHD) and
      influences the course of the disease, but no randomized controlled trial has
      investigated the effects of a psychotherapy intervention in CHD patients with
      elevated anxiety scores. The main aim of this study was to evaluate the effects
      of a 6-month psychotherapy intervention on anxiety in this group of patients.
      METHODS: Fifty-two patients (61 +/- 8.0 years, 14 female) with CHD and elevated
      levels of anxiety completed the study after randomization into a 6-month
      psychotherapy intervention or a control condition. Medically eligible patients
      were screened for anxiety with the Hospital Anxiety and Depression Scale (HADS)
      and were included if they had a score of 8 or higher. Anxiety scores were
      reevaluated at 6-month follow-up (after the treatment). RESULTS: At 6-month
      follow-up significant reductions (intervention group: -2.0 +/- 2.3; control
      group: -1.8 +/- 2.8; p < 0.01) were found in both groups in the HADS anxiety
      scale but no significant differences between the groups were observed. Adjustment
      for baseline differences and disease severity did not change these results.
      CONCLUSIONS: Our study showed that elevated anxiety scores were reduced over time
      but there was no statistically significant effect of the psychotherapy
      intervention in anxious patients with CHD. Changes in the design of the
      intervention and study might be useful to further investigate this topic in the
      future.

PMID- 21968459
TI  - Effect of mouth rinses with fluoride and trimetaphosphate on enamel erosion: an
      in vitro study.
AB  - The effect of mouth rinses containing fluoride (100 MUg/ml) and sodium
      trimetaphosphate (TMP) on enamel erosion was evaluated in vitro. Bovine enamel
      blocks were subjected to erosive challenges 4 times per day for 5 min, followed
      by treatment with placebo, 225 MUg F/ml, 100 MUg F/ml, 100 MUg F/ml and TMP (0.2,
      0.4 and 0.6%) solutions (30 s) and storage in artificial saliva, over a duration
      of 5 days. TMP groups showed lower enamel wear than fluoride-only and placebo
      groups (p < 0.05). Addition of TMP at a TMP:NaF molar proportion between 1.24:1
      and 3.72:1 to a solution containing 100 MUg F/ml presented a greater protective
      effect under erosive conditions than a solution containing 225 MUg F/ml, in the
      absence of TMP.

PMID- 21968460
TI  - Prevalence and factors associated with HSV-2 and hepatitis B infections among
      truck drivers crossing the southern Brazilian border.
AB  - OBJECTIVES: The authors estimate the prevalence of HIV, syphilis, hepatitis B
      virus (HBV) and herpes simplex virus type-2 (HSV-2) infection and correlates of
      HBV and HSV-2 infection among truck drivers crossing the southern Brazilian
      border at Foz do Iguacu. METHODS: Between October 2003 and March 2005, 1945 truck
      drivers were sampled while accessing voluntary counselling and testing services;
      1833 (94.2%) were tested for HIV (ELISA and confirmatory immunofluorescence
      assay) and syphilis (non-treponemal (VDRL) and treponemal tests (FTA-ABS)). From
      these, 799 stored sera were tested for HSV-2 (type-specific ELISA test for
      detection of IgG) and HBV (core antibodies (anti-HBc) with positives tested for
      surface antigen (HBsAg)). The authors estimate HIV, syphilis, HSV-2 and HBV
      prevalence and determine socio-demographic and behavioural correlates of HSV-2
      infection and HBV exposure. RESULTS: HIV prevalence was 0.3% (95% CI 0.1 to 0.6)
      and syphilis 4.5% (95% CI 3.6 to 5.4). Among those tested for HBV and HSV-2,
      32.3% (95% CI 28.9 to 35.6) had serological evidence of exposure to HBV and 26.6%
      (95% CI 23.5 to 29.7) tested positive for HSV-2. Factors independently associated
      with HBV exposure included increasing age, Brazilian nationality and unprotected
      anal sex. Increasing age and reporting an unknown number of lifetime partners
      were associated with HSV-2 infection. CONCLUSIONS: In this sample of truck
      drivers in southern Brazil, HIV prevalence was lower than national population
      estimates; exposure to HBV was higher than population estimates, while per cent
      positive for HSV-2 was similar to population estimates. The low prevalence of HIV
      in truck drivers indicates prevention successes; however, future HIV prevention
      programming should incorporate HBV vaccination and sexually transmitted infection
      prevention.

PMID- 21968461
TI  - Educational level and HIV disease progression before and after the introduction
      of HAART: a cohort study in 989 HIV seroconverters in Spain.
AB  - OBJECTIVES: To analyse the effect of educational level on the progression from
      HIV seroconversion to highly active antiretroviral therapy (HAART) requirement,
      HAART initiation, AIDS and death from any cause at different periods of the HIV
      epidemic in Spain. METHODS: Open, prospective, multicentre cohort of HIV
      seroconverters set up in 1983. The risk of progression was calculated by the
      multiple decrements method. Effect of educational level was estimated by Fine and
      Gray model, adjusting for sex, HIV transmission category, age and method to
      estimate seroconversion. Calendar period was introduced as a variable that could
      change over time (<1997; 1997-2003; >2003). RESULTS: Up to 2009, 989 HIV
      seroconverters with information on educational level were identified. Some 52%
      and 48% had a low and a high educational level respectively. Persons with higher
      education had 32% lower risk of death (HR: 0.68; 95% CI 0.45 to 1.03). Regarding
      progression to AIDS, educational level had no effect in the pre-HAART era (HR:
      1.47; 95% CI 0.91 to 2.38), but did show an effect in the period 1997-2003 (HR:
      0.58; 95% CI 0.34 to 0.99), which was accentuated after 2004 (HR: 0.26; 95% CI
      0.10 to 0.68). No difference was found in time to HAART requirement or
      initiation. CONCLUSIONS: Results suggest that, despite similar access to HAART,
      persons with low educational level are at increased risk of HIV disease
      progression, highlighting the impact of social inequities on health. The
      availability of more effective treatments over time will strengthen the
      protective effect of higher education on the development of AIDS.

PMID- 21968462
TI  - Using a comparative species approach to investigate the neurobiology of paternal
      responses.
AB  - A goal of behavioral neuroscience is to identify underlying neurobiological
      factors that regulate specific behaviors.  Using animal models to accomplish this
      goal, many methodological strategies require invasive techniques to manipulate
      the intensity of the behavior of interest (e.g., lesion methods, pharmacological
      manipulations, microdialysis techniques, genetically-engineered animal models).
      The utilization of a comparative species approach allows researchers to take
      advantage of naturally occurring differences in response strategies existing in
      closely related species.  In our lab, we use two species of the Peromyscus genus
      that differ in paternal responses.  The male California deer mouse (Peromyscus
      californicus) exhibits the same parental responses as the female whereas its
      cousin, the common deer mouse (Peromyscus maniculatus) exhibits virtually no
      nurturing/parental responses in the presence of pups.  Of specific interest in
      this article is an exploration of the neurobiological factors associated with the
      affiliative social responses exhibited by the paternal California deer mouse. 
      Because the behavioral neuroscience approach is multifaceted, the following key
      components of the study will be briefly addressed:   the identification of
      appropriate species for this type of research; data collection for behavioral
      analysis; preparation and sectioning of the brains; basic steps involved in
      immunocytochemistry for the quantification of vasopressin-immunoreactivity; the
      use of neuroimaging software to quantify the brain tissue; the use of a
      microsequencing video analysis to score behavior and, finally, the appropriate
      statistical analyses to provide the most informed interpretations of the research
      findings.

PMID- 21968463
TI  - Phase I study of two schedules of oral S-1 in combination with fixed doses of
      oxaliplatin and bevacizumab in patients with advanced solid tumors.
AB  - BACKGROUND: S-1 is a novel oral agent combining the 5-fluorouracil (FU) prodrug
      tegafur with gimeracil and oteracil, which inhibit 5-FU degradation by
      dihydropyrimidine dehydrogenase and phosphorylation within the gastrointestinal
      tract, respectively. The study was designed to identify the maximum tolerable
      dose and the dose-limiting toxicities of two schedules of S-1 combined with
      oxaliplatin and bevacizumab, in advanced solid tumor patients. METHODS: Schedule
      A: S-1 was administered orally at 20 mg/m(2) twice daily for 14 consecutive days,
      escalated by 5 mg/m(2), with fixed-dose intravenous bevacizumab 7.5 mg/kg and
      oxaliplatin 130 mg/m(2) on day 1 of each 3-week cycle. Schedule B: S-1 was
      administered at 25 mg/m(2) twice daily for 7 consecutive days, escalated by 5
      mg/m(2), with fixed-dose intravenous bevacizumab 5 mg/kg and oxaliplatin 85
      mg/m(2) on day 1 of each 2-week cycle. RESULTS: The maximum tolerated dose and
      recommended phase II dose of S-1 was 25 mg/m(2) twice daily for 14 days for
      schedule A and 35 mg/m(2) twice daily for 7 days for schedule B. The most common
      dose-limiting toxicities were grade 3 diarrhea. Both regimens were well
      tolerated. No pharmacokinetic interactions between oxaliplatin and S-1 components
      were observed. CONCLUSIONS: S-1, oxaliplatin and bevacizumab can be administered
      with acceptable safety and tolerability and without evidence of pharmacokinetic
      interactions.

PMID- 21968464
TI  - A two-stage model for the SIR outbreak: accounting for the discrete and
      stochastic nature of the epidemic at the initial contamination stage.
AB  - The evolution of an infectious disease outbreak in an isolated population is
      split into two stages: a stochastic Markov process describing the initial
      contamination and a linked deterministic dynamical system with random initial
      conditions for the continued development of the outbreak. The initial
      contamination stage is well approximated by the randomized SI
      (susceptible/infected) model. We obtain the probability density function for the
      early behavior of the epidemic. This provides an appropriate distribution for the
      initial conditions with which to describe the subsequent deterministic evolution
      of the system. We apply the method of matching asymptotic expansions to link the
      two stages. This allows us to estimate the standard deviation of the number of
      infectives in the developed outbreak, and the statistical characteristics of the
      outbreak time. The potential trajectories caused by the stochastic nature of the
      contamination stage show greatest divergence at the initial and fade-out stages
      and coincide most tightly just after the peak of the epidemic. The time to the
      peak of the outbreak is not strongly dependent on the initial trajectory.

PMID- 21968465
TI  - Innovative community-based initiatives to engage VFR travelers.
AB  - This report describes novel initiatives to inform ethnic groups contributing high
      numbers of VFRs about potential travel risks. Multilingual and culturally
      appropriate information was distributed to the media (newspaper, radio, web
      based, and television), via printed materials (posters, tear sheets and z-cards)
      and at community festivals to convey simple travel health messages.

PMID- 21968466
TI  - Decarboxylative Claisen rearrangement reactions: synthesis and reactivity of
      alkylidene-substituted indolines.
AB  - Microwave-assisted decarboxylative Claisen rearrangement (dCr) reactions of
      substituted acetate derivatives of 3-(hydroxyalkyl)indoles give de-aromatised
      products. The reactivity of the resultant compounds was evaluated.

PMID- 21968468
TI  - Characterization of kidney stones using thermogravimetric analysis with electron
      dispersive spectroscopy.
AB  - Urinary calculi are formed from a result of biological mal-adjustment of urine
      leading to deposits of salt and mineral crystals along the urinary collecting
      system. They are usually multiphasic material with complex compositions. The
      objective of this study is to identify and characterize a series of urinary
      calculi samples using a combination of thermogravimetric analysis (TGA) with
      electron dispersive spectroscopy (EDS). These samples were retrieved during
      percutaneous nephrolithotripsy. Additional characterization by hardness value and
      microstructure is also carried out for co-relation study. The samples are found
      to be uric acid, calcium oxalates and magnesium ammonium phosphate hexahydrate.
      TGA is indeed one of the viable analytical tools for urinary calculi as it is
      fast and simple. The combinational application of EDS is beneficial when there is
      a need for differentiated qualitative chemical composition detection at the
      identified nuclei position for urinary calculi with spatial variation in
      composition. The combination of TGA and EDS will thus facilitate the correct
      diagnosis and treatment by clinicians.

PMID- 21968467
TI  - Sputum YKL-40 levels and pathophysiology of asthma and chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Recent evidence suggests that YKL-40, also called chitinase-3-like-1
      protein, is involved in the pathogenesis of asthma and chronic obstructive
      pulmonary disease (COPD). Details of sputum YKL-40 in asthma and COPD, however,
      remain unknown. OBJECTIVES: To clarify associations of sputum YKL-40 levels with
      clinical indices in asthma and COPD. METHODS: Thirty-nine patients with asthma,
      14 age-matched never-smokers as controls, 45 patients with COPD, and 7 age
      matched smokers as controls were recuited for this study. Sputum YKL-40 levels
      were measured and YKL-40 expression in sputum cells was evaluated by
      immunocytochemistry. RESULTS: Sputum YKL-40 levels were higher in patients with
      COPD (346 +/- 325 ng/ml) than in their smoker controls (125 +/- 122 ng/ml; p <
      0.05), but were not significantly different between patients with asthma (117 +/-
      170 ng/ml) and their controls (94 +/- 44 ng/ml; p = 0.15). In patients with
      asthma only, sputum YKL-40 levels were positively correlated with disease
      severity (r = 0.34, p = 0.034) and negatively correlated with pre- and
      postbronchodilator %FEV(1) (r = -0.47 and -0.42, respectively; p < 0.01) and
      forced mid-expiratory flow (r = -0.48 and -0.46, respectively, p < 0.01). Sputum
      YKL-40 levels were positively correlated with sputum neutrophil counts in asthma
      (r = 0.55, p < 0.001) and with neutrophil and macrophage counts in COPD (r = 0.45
      and 0.65, respectively, p < 0.01). YKL-40 was expressed in the cytoplasm of
      sputum neutrophils and macrophages in all groups. CONCLUSIONS: Elevated sputum
      YKL-40 reflects airflow obstruction in asthma whereas the roles of YKL-40 in the
      proximal airways in COPD remain to be elucidated.

PMID- 21968469
TI  - A discussion of dissection.

PMID- 21968470
TI  - Necrotic skin lesions after hemodialysis.

PMID- 21968471
TI  - Q: What is the best questionnaire to screen for alcohol use disorder in an office
      practice?

PMID- 21968472
TI  - Dabigatran: will it change clinical practice?
AB  - Dabigatran (Pradaxa) is a new oral anticoagulant approved in the United States
      for the primary prevention of stroke and systemic embolization in patients with
      nonvalvular atrial fibrillation. It offers clinicians an alternative to warfarin
      (Coumadin), and it has received considerable interest because of its convenience
      of use, clinical efficacy, and safety profile. However, it is more expensive, and
      this may limit its widespread use.

PMID- 21968473
TI  - Update in intensive care medicine: studies that challenged our practice in the
      last 5 years.
AB  - During the last 5 years, new randomized trials in critically ill patients have
      challenged a number of traditional treatment strategies in intensive care. The
      authors review eight studies that helped change their medical practices.

PMID- 21968475
TI  - Aortic dissection: prompt diagnosis and emergency treatment are critical.
AB  - Diagnosing aortic dissection requires a high index of suspicion, as it may mimic
      other more common conditions that cause chest pain. Prompt diagnosis is key, as
      it requires emergency evaluation and treatment for optimal chances of survival.
      This paper reviews key clinical features as well as laboratory and imaging tests.

PMID- 21968474
TI  - Jet lag and shift work sleep disorders: how to help reset the internal clock.
AB  - Jet lag sleep disorder and shift work sleep disorder are the result of
      dyssynchrony between the internal clock and the external light-dark cycle,
      brought on by rapid travel across time zones or by working a nonstandard
      schedule. Symptoms can be minimized by optimizing the sleep environment, by
      strategic avoidance of and exposure to light, and also with drug and behavioral
      therapies.

PMID- 21968476
TI  - A new ICU paradigm: intensivists as primary critical care physicians.

PMID- 21968477
TI  - In-line prediction of drug release profiles for pH-sensitive coated pellets.
AB  - A new method for the prediction of the drug release profiles during a running
      pellet coating process from in-line near infrared (NIR) measurements has been
      developed. The NIR spectra were acquired during a manufacturing process through
      an immersion probe. These spectra reflect the coating thickness that is
      inherently connected with the drug release. Pellets sampled at nine process time
      points from thirteen designed laboratory-scale coating batches were subjected to
      the dissolution testing. In the case of the pH-sensitive Acryl-EZE coating the
      drug release kinetics for the acidic medium has a sigmoid form with a pronounced
      induction period that tends to grow along with the coating thickness. In this
      work the autocatalytic model adopted from the chemical kinetics has been
      successfully applied to describe the drug release. A generalized interpretation
      of the kinetic constants in terms of the process and product parameters has been
      suggested. A combination of the kinetic model with the multivariate Partial Least
      Squares (PLS) regression enabled prediction of the release profiles from the
      process NIR data. The method can be used to monitor the final pellet quality in
      the course of a coating process.

PMID- 21968478
TI  - Breastfeeding and offspring hostility in adulthood.

PMID- 21968479
TI  - Characterization of a recombinant (-)gamma-lactamase from Microbacterium
      hydrocarbonoxydans.
AB  - A (-)gamma-lactamase, Mhg, from Microbacterium hydrocarbonoxydans was over
      expressed in E. coli and was characterized after purification. The maximum
      activity was at pH 8.0 and 60 degrees C and the half life of Mhg was ~30 min at
      75 degrees C. The enzyme was activated by DTT. The catalytic triad of the (
      )gamma-lactamase is comprised of residues Ser98, Asp230, and His259 and an
      oxyanion hole was formed by Tyr32 and Met99 according to the alignment results.
      Under native conditions, the (-)gamma-lactamase consists of two 31 kDa
      homodimers.

PMID- 21968480
TI  - Expression and purification of two alternative peptides for mechano-growth factor
      in Escherichia coli.
AB  - Two genes, MGFc (40) and MGFc (24), encoding different E peptides of mechano
      growth factor (MGF), were obtained by a four-step PCR strategy and subcloned into
      pRSETC and pGEX-6p-1. Recombinant MGFc(40) protein (4 mg l(-1)) was expressed and
      purified by affinity chromatography using His60 Ni Superflow. Recombinant
      MGFc(24) protein was purified using a glutathione-Sepharose 4B column. After
      enzymatic cleavage of the GST-tail, 1 mg MGFc(24) protein l(-1) was obtained.
      MGFc(40) and MGFc(24), which are involved in proliferation and differentiation,
      stimulated cell proliferation and inhibited cell differentiation of C2C12 cells.

PMID- 21968481
TI  - Protected health information on ultrasound images: time to end the burn.

PMID- 21968482
TI  - A novel nanosonosensitizer for sonodynamic therapy: in vivo study on a colon
      tumor model.
AB  - OBJECTIVES: The particles in a liquid decrease the ultrasonic intensity threshold
      needed for cavitation onset. In this study, a new nanoconjugate composed of
      protoporphyrin IX and gold nanoparticles was used as a nucleation site for
      cavitation. The nonradiative relaxation time of protoporphyrin IX in the presence
      of gold nanoparticles is longer than the similar time without gold nanoparticles.
      METHODS: This study was conducted on colon carcinoma tumors in BALB/c mice. The
      tumor-bearing mice were randomly divided into 6 groups (each containing 15 mice):
      (1) control, (2) protoporphyrin IX, (3) gold nanoparticle-protoporphyrin IX
      conjugate, (4) ultrasound alone, (5) ultrasound + protoporphyrin IX, and (6)
      ultrasound + gold nanoparticle-protoporphyrin IX conjugate. In the respective
      groups as indicated above, protoporphyrin IX or the gold nanoparticle
      protoporphyrin IX conjugate was injected into the tumors. Ultrasound irradiation
      was performed on the tumors 24 hours after injection. Antitumor effects were
      estimated by evaluation of the relative tumor volume, doubling time, and 5
      folding time for the tumors after treatment. The cumulative survival fraction of
      the mice and percentage of the lost tissue volume (treated) were also assessed in
      the different groups. RESULTS: A significant difference in the average relative
      volumes of the tumors 13 days after treatment was found between the ultrasound +
      gold nanoparticle-protoporphyrin IX group and the other groups (P < .05). The
      longest doubling and 5-folding times were observed in the ultrasound + gold
      nanoparticle-protoporphyrin IX and ultrasound + protoporphyrin IX groups.
      CONCLUSIONS: Protoporphyrin IX conjugated to gold nanoparticles has been
      introduced as a promising compound and a new sonosensitizer for improving the
      tumor response to sonodynamic therapy by reducing the relative tumor volume and
      increasing the cumulative survival fraction.

PMID- 21968483
TI  - Objective sonographic measures for characterizing myofascial trigger points
      associated with cervical pain.
AB  - OBJECTIVES: The purpose of this study was to determine whether the physical
      properties and vascular environment of active myofascial trigger points
      associated with acute spontaneous cervical pain, asymptomatic latent trigger
      points, and palpably normal muscle differ in terms of the trigger point area,
      pulsatility index, and resistivity index, as measured by sonoelastography and
      Doppler imaging. METHODS: Sonoelastography was performed with an external 92-Hz
      vibration in the upper trapezius muscles in patients with acute cervical pain and
      at least 1 palpable trigger point (n = 44). The area of reduced vibration
      amplitude was measured as an estimate of the size of the stiff myofascial trigger
      points. Patients also underwent triplex Doppler imaging of the same region to
      analyze blood flow waveforms and calculate the pulsatility index of blood flow in
      vessels at or near the trigger points. RESULTS: On sonoelastography, active sites
      (spontaneously painful with palpable myofascial trigger points) had larger
      trigger points (mean +/- SD, 0.57 +/- 0.20 cm(2)) compared to latent sites
      (palpable trigger points painful on palpation; 0.36 +/- 0.16 cm(2)) and palpably
      normal sites (0.17 +/- 0.22 cm(2); P < .01). Analysis of receiver operating
      characteristic curves showed that area measurements could robustly distinguish
      between active, latent, and normal sites (areas under the curve, 0.9 for active
      versus latent, 0.8 for active versus normal, and 0.8 for latent versus normal,
      respectively). Doppler spectral waveform data showed that vessels near active
      sites had a significantly higher pulsatility index (median, 8.3) compared to
      normal sites (median, 3.0; P < .05). CONCLUSIONS: The results presented in this
      study show that myofascial trigger points may be classified by area using
      sonoelastography. Furthermore, monitoring the trigger point area and pulsatility
      index may be useful in evaluating the natural history of myofascial pain
      syndrome.

PMID- 21968484
TI  - Ultrasound-guided treatment of meralgia paresthetica (lateral femoral cutaneous
      neuropathy): technical description and results of treatment in 20 consecutive
      patients.
AB  - OBJECTIVES: The purposes of this study were to describe a technique for treatment
      of meralgia paresthetica (lateral femoral cutaneous neuropathy) using ultrasound
      guidance and to report the results of treatment. METHODS: Twenty consecutive
      patients (7 male and 13 female; age range, 23-66 years; mean, 39 years) with
      meralgia paresthetica confirmed by electromyography were treated with perineural
      injection of 1 mL of methylprednisolone acetate (40 mg/mL) and 8 mL of
      mepivacaine, 2%, under direct ultrasound guidance. Main outcome measures included
      the technical success of the procedure, visual analog scale score for the lateral
      femoral cutaneous nerve (pain, burning sensation, and paresthesia), and visual
      analog scale global quality of life score. RESULTS: Technical success (successful
      nerve block at the distribution of the lateral femoral cutaneous nerve) was
      achieved in all patients. Five patients felt slight sharp pain during needle
      insertion. The symptoms in 16 patients (80%) diminished progressively after the
      first week. The 4 remaining patients (20%) required a further perineural
      injection. The symptoms disappeared in all patients 2 months after injection
      (mean visual analog scale score +/- SD for lateral femoral cutaneous neuropathy
      at baseline, 8.1 +/- 2.1; at 2 months, 2.1 +/- 0.5; t = 6.2; P < .001). The mean
      visual analog scale quality of life scored decreased from 6.9 +/- 3.2 to 2.3 +/-
      2.5 (t = 5.3; P < .002). CONCLUSIONS: Treatment of meralgia paresthetica with
      ultrasound-guided perineural injections resulted in substantial symptom relief in
      most patients 2 months after injection. Randomized placebo-controlled trials of
      this treatment should be considered in the future.

PMID- 21968485
TI  - Sonography of partial-thickness tears of the distal triceps brachii tendon.
AB  - OBJECTIVES: The purpose of this study was to retrospectively characterize the
      sonographic appearance of partial-thickness distal triceps brachii tendon tears.
      METHODS: After Institutional Review Board approval, sonographic records were
      searched for patients who had an unequivocal partial-thickness triceps tendon
      tear at surgery or magnetic resonance imaging. Sonograms were retrospectively
      characterized for tendon discontinuity of the superficial or deep layers, tendon
      retraction, osseous fracture fragments, and joint effusion. Imaging findings were
      then compared with clinical, imaging, and surgical results. RESULTS: Five
      patients had a partial-thickness distal triceps brachii tendon tear at surgery (n
      = 4) or magnetic resonance imaging (n = 1). All cases only involved the
      superficial tendon layer (combined long and lateral heads) with retraction of a
      fractured olecranon enthesophyte fragment. The deep tendon layer (medial head)
      was intact in all cases with no joint effusion. CONCLUSIONS: Partial-thickness
      distal triceps brachii tendon tears have a characteristic appearance with
      selective superficial tendon retraction and olecranon enthesophyte avulsion
      fracture.

PMID- 21968486
TI  - Comparison of procedural times for ultrasound-guided perineural catheter
      insertion in obese and nonobese patients.
AB  - OBJECTIVES: Perineural catheter insertion with ultrasound guidance alone has been
      described, but it remains unknown whether this new technique results in the same
      procedural time and success rate for obese and nonobese patients. We therefore
      tested the hypothesis that obese patients require more time for perineural
      catheter insertion compared to nonobese patients despite using ultrasound.
      METHODS: Data from 5 previously published randomized clinical trials comparing
      ultrasound- and stimulation-guided perineural catheter insertion techniques were
      reviewed, and patients who received ultrasound-guided catheters were divided into
      2 groups: obese (body mass index >=30 kg/m(2)) and nonobese (body mass index <30
      kg/m(2)). A standardized ultrasound-guided nonstimulating catheter technique was
      used with mepivacaine, 1.5% (40 mL), as the initial bolus via the placement
      needle for the primary surgical nerve block. The primary outcome was the
      procedural time for perineural catheter insertion. Secondary outcomes included
      block efficacy, procedure-related pain, fluid leakage, vascular puncture, and
      catheter dislodgment. RESULTS: A sample of 120 patients was identified: 51 obese
      and 69 nonobese. All obese patients had successful catheter placement compared to
      68 of 69 (98%) nonobese patients (P = .388). The time for perineural catheter
      insertion [median (10th-90th percentiles)] was 7 (4-12) minutes for obese
      patients versus 7 (4-15) minutes for nonobese patients (P = .732). There were no
      statistically significant differences in other secondary outcomes. CONCLUSIONS:
      On the basis of this retrospective analysis, perineural catheter insertion is not
      prolonged in obese patients compared to nonobese patients when an ultrasound
      guided technique is used. However, these results are only suggestive and require
      confirmation through prospective study.

PMID- 21968487
TI  - Correlation between a semiautomated method based on ultrasound texture analysis
      and standard ultrasound diagnosis using white matter damage in preterm neonates
      as a model.
AB  - OBJECTIVES: Diagnosis of white matter damage by cranial ultrasound imaging is
      still subject to interobserver variability and has limited sensitivity for
      predicting abnormal neurodevelopment later in life. In this study, we evaluated
      the ability of a semiautomated method based on ultrasound texture analysis to
      identify patterns that correlate with the ultrasound diagnosis of white matter
      damage. METHODS: The study included 44 very preterm neonates born at a median
      gestational age of 29 weeks 3 days (range, 26 weeks-31 weeks 6 days). Patients
      underwent cranial ultrasound scans within 1 week of birth and between 14 and 31
      days of life. Periventricular leukomalacia was diagnosed by experienced
      clinicians on the 14- to 31-day scan according to standard criteria. To perform
      the texture analysis, 4 regions of interest were delineated in stored images:
      left and right periventricular areas and choroid plexuses. A classification
      algorithm was developed on the basis of the best combination of texture
      coefficients to correlate with the clinical diagnosis, and the ability of this
      algorithm to predict a later diagnosis of periventricular leukomalacia on the
      first scan was evaluated using a leave-one-out cross-validation. RESULTS:
      Periventricular leukomalacia was diagnosed by the standard procedure in 14 of 44
      neonates. The texture classification algorithm performed on the first scan could
      identify cases with a later diagnosis of periventricular leukomalacia with
      sensitivity of 100% and accuracy of 97.7%. CONCLUSIONS: These data support the
      notion that semiautomated quantitative ultrasound analysis achieves early
      identification of changes in subclinical stages and warrant further investigation
      of the role of ultrasound texture analysis methods to improve early detection of
      neonatal brain damage.

PMID- 21968488
TI  - Adding cancer antigen 125 screening to gray scale sonography for predicting
      specific diagnosis of benign adnexal masses in premenopausal women: is it
      worthwhile?
AB  - OBJECTIVES: The purpose of this study was to assess whether a single
      determination of the serum cancer antigen 125 (CA-125) level provides additional
      information to sonography for specific diagnosis of benign adnexal masses in
      premenopausal women. METHODS: We conducted a retrospective study comprising 1058
      premenopausal women (mean age, 34.8 years) with histologically proven benign
      adnexal masses. All women had undergone transvaginal sonography and serum CA-125
      determination within 1 week before surgery and tumor removal. According to
      "pattern recognition" analysis, a presumptive diagnosis was provided on gray
      scale transvaginal sonography for all masses. Positive and negative likelihood
      ratios were calculated for gray scale sonography and gray scale sonography plus
      CA-125. RESULTS: Eighty-five women had bilateral masses (1143 masses analyzed).
      In 7 women with bilateral masses, the histologic diagnoses of the masses were
      discordant and were excluded. Histologic diagnoses were as follows: endometrioma,
      n = 452; dermoid cyst, n = 180; serous cyst, n = 158; hemorrhagic cyst, n = 119;
      mucinous cyst, n = 54; hydrosalpinx, n = 37; and other, n = 109. The median CA
      125 level was significantly higher in endometrioma (71.9 IU/mL; range: 5-2620
      IU/mL) and hydrosalpinx (59.2 IU/mL; range, 5-601 IU/mL) compared to all other
      tumor types (P < .001). The CA-125 level was 35 IU/mL or higher in 74% of
      endometriomas, 58% of hydrosalpinges, 34% of hemorrhagic cysts, 18% of mucinous
      cysts, 14% of dermoid cysts, and 8% of serous cysts. The positive and negative
      likelihood ratios for sonography and sonography plus CA-125 (335 IU/mL) for each
      kind of tumor were not statistically different except for endometrioma, for which
      the positive likelihood ratio for sonography plus CA-125 (55.0; 95% confidence
      interval, 27.5-109.9) was significantly higher than for sonography alone (19.2;
      95% confidence interval, 13.6-27.1). CONCLUSIONS: Cancer antigen 125 screening
      does not add useful information for specific diagnosis of benign adnexal tumors,
      except for endometrioma. An elevated CA-125 level significantly increases the
      probability of such a lesion.

PMID- 21968489
TI  - Mobile echogenicities on scrotal sonography: is the finding associated with
      vasectomy?
AB  - OBJECTIVES: The purpose of this study was to determine whether mobile
      echogenicities seen in the epididymis on scrotal sonography are associated with
      prior vasectomy. METHODS: We prospectively obtained a sonographic video clip of
      each epididymal body in outpatients sent for scrotal sonography. The presence of
      punctate mobile echogenicities in the epididymal body was noted, and the
      indication for the sonogram, patient age, and history of vasectomy were recorded.
      This study was compliant with the Health Insurance Portability and Accountability
      Act and was approved by the Institutional Review Board. RESULTS: Of 345 patients
      (mean age, 44.9 years), 56 (16.2%) had undergone vasectomy and 289 had not.
      Mobile echogenicities were found in 8 patients, 7 of whom were postvasectomy. The
      rates of mobile echogenicities appearing were 12.5% (7 of 56) in the vasectomy
      group and 0.3% (1 of 289) in the nonvasectomy group (P < .0001, Fisher exact
      test). Epididymal cysts were seen in 184 of 345 patients (53.3%). There was no
      significant difference in the presence of epididymal cysts in the patients who
      had undergone vasectomy compared to those who had not (P = .34), including 30 of
      56 postvasectomy patients (53.6%) and 154 of 289 patients without vasectomy
      (53.3%). Pain was reported by 177 patients (51.3%), including 34 of 56 (60.7%) in
      the postvasectomy group and 143 of 289 (49.5%) without vasectomy. The presence of
      pain was similar in both groups (P = .15). CONCLUSIONS: The presence of mobile
      echogenicities in the epididymis is almost always a postvasectomy finding and
      occurs in approximately 12.5% of such patients. There is no significant
      difference in the rate of epididymal cysts or pain after vasectomy compared to
      those who have not had vasectomies.

PMID- 21968490
TI  - Sonography of intrascrotal appendage torsion: varying echogenicity of the torsed
      appendage according to the time from onset.
AB  - OBJECTIVES: The purpose of this study was to evaluate sonographic findings in
      torsed intrascrotal appendages and to assess the effect of the time from symptom
      onset on echogenicity and the relationship between the time from symptom onset
      and manual reduction success. METHODS: Thirty-five boys (6-13 years old; mean,
      9.9 years) with torsion of an intrascrotal appendage were evaluated. All had
      painful unilateral scrotal swelling and palpable tender nodules on physical
      examination and underwent sonography. Thirty-two underwent subsequent manual
      reduction. Before manual reduction, we assessed the size, echogenicity, appendage
      blood flow, periappendiceal blood flow, and scrotal swelling. Data were analyzed
      according to time from symptom onset. After manual reduction, the number of
      reduction trials, pain relief, size, and blood flow of the appendix testis were
      assessed. RESULTS: The torsed appendage was hypoechoic in all 17 boys assessed
      within 24 hours of symptom onset. In boys assessed more than 24 hours after
      onset, the torsed appendage was hypoechoic in 6, isoechoic in 4, and hyperechoic
      in 8. Twenty-two of 23 hypoechoic appendages showed a salt-and-pepper pattern.
      The echogenicity differed significantly between boys assessed within and more
      than 24 hours after symptom onset (P < .001). The success rates of manual
      reduction were 90.9% (20 of 22) for hypoechoic appendages, 75.0% (3 of 4) for
      isoechoic appendages, and 50.0% (3 of 6) for hyperechoic appendages. Sonography
      revealed increased blood flow and decreased appendage sizes in all boys with
      successful reduction. CONCLUSIONS: The echogenicity of a torsed appendage changes
      according to the time from onset. A hyperechoic intrascrotal appendage is
      associated with later sonography and is a poor predictor of manual reduction
      success.

PMID- 21968491
TI  - Prenatal diagnosis of penoscrotal transposition with 2- and 3-dimensional
      ultrasonography.
AB  - OBJECTIVES: The purpose of this study was to determine the prenatal diagnostic
      accuracy of 2-dimensional ultrasonography (2DUS) alone versus 2DUS in combination
      with 3-dimensional ultrasonography (3DUS) for penoscrotal transposition. METHODS:
      Fetuses suspected of having penoscrotal transposition on the basis of
      ultrasonographic findings or a family history were examined by 2DUS and then
      3DUS. RESULTS: Of a total of 22 fetuses, 14 had penoscrotal transposition at
      birth. The combination of 2DUS and 3DUS correctly identified more of the
      penoscrotal transposition cases than 2DUS alone (90.9% versus 63.6%; P < .05).
      CONCLUSIONS: The combination of 2DUS and 3DUS improved the prenatal detection
      rate for penoscrotal transposition compared with 2DUS alone.

PMID- 21968493
TI  - Spatiotemporal image correlation artifacts in an in vitro model.
AB  - An experimental in vitro setting with a latex miniature balloon was designed to
      test the accuracy of volumetric measurements by spatiotemporal image correlation.
      Two-dimensional images clearly showed the round balloon as a thin echogenic ring
      in a translucent area. Four-dimensional reconstructed images, however, showed a
      severely distorted balloon. The artifacts disappeared when the surroundings of
      the balloons were made echogenic, mimicking the in vivo setting. We hypothesize
      that the artifacts were the result of gating errors. These experiments can be
      relevant for analysis of spatiotemporal image correlation volumes in daily
      practice.

PMID- 21968492
TI  - Vermian biometric parameters in the normal and abnormal fetal posterior fossa:
      three-dimensional sonographic study.
AB  - OBJECTIVES: The purposes of this study were to describe a 3-dimensional
      sonographic technique for evaluation of the fetal vermis and to compare vermian
      biometric parameters in fetuses with a normal and an abnormal posterior fossa.
      METHODS: A prospective study was conducted from 2006 through 2008 on 12 fetuses
      with an abnormal posterior fossa and 73 healthy control fetuses from 18 to 35
      weeks' gestation. Three-dimensional scans of the fetal head were performed in the
      axial plane, using static volume contrast imaging in the C-plane. The vermian
      perimeter, cross-sectional area, and superoinferior diameter were measured and
      compared between abnormal and normal fetuses using the Wilcoxon nonparametric
      test. Linear regression analysis was used to describe trends of the vermis during
      gestation. The z scores for perimeter, cross-sectional area, and superoinferior
      diameter measurements in the abnormal posterior fossa group in each 2-week
      interval were calculated. RESULTS: Twelve fetuses with an abnormal posterior
      fossa were recruited: 3 with a Blake pouch cyst, 1 vermian cyst, 1 enlarged
      cisterna magna, 2 Dandy-Walker malformation, 4 partial vermian agenesis, and 1
      hemicerebellar hypoplasia. The vermian cross-sectional area was reduced
      significantly in the fetuses with an abnormal posterior fossa compared with the
      control fetuses starting at 18 to 19 weeks' gestation (P = .01); the mean vermian
      superoinferior diameter was lower only from 22 to 23 weeks (P = .01); and the
      mean vermian perimeter was decreased from 28-29 weeks' gestation (P = .03).
      Linear regression analysis of the parameters showed that fetuses with an abnormal
      posterior fossa had a statistically significantly lower growth rate than control
      fetuses during gestation (P < .001). CONCLUSIONS: Measurements of the cross
      sectional area were more useful than those of the perimeter and superoinferior
      diameter in distinguishing between fetuses with a normal and an abnormal
      posterior fossa during the early stages of gestation.

PMID- 21968494
TI  - Statistical analysis and interpretation of prenatal diagnostic imaging studies,
      part 3: approach to study design.
AB  - A critical step in planning a successful study is choosing the appropriate design
      to feasibly answer the clinical question at hand. We provide an overview of
      common study designs, discuss their advantages and disadvantages, and provide
      practical examples from the prenatal diagnosis and ultrasound literature. In
      addition, we highlight specific design considerations that need to be built into
      the analysis of study results.

PMID- 21968495
TI  - Unexpected findings on point-of-care superficial ultrasound imaging before
      incision and drainage.
AB  - Cutaneous abscesses are typically incised and drained on the basis of clinical
      assessment. In most cases this procedure is a safe practice. We report 6 cases in
      which point-of-care ultrasound interrogation of obvious abscesses revealed
      potential serious complications with planned incision and drainage. Management
      was altered in 5 of 6 cases, and potential vascular disasters were avoided. In 1
      case, the ultrasound results were ignored, and incision and drainage was
      completed, confirming the suspected abscess was indeed a solid mass later
      diagnosed as a carcinoma. In this case series, point-of-care ultrasound
      interrogation provided rapid assessment and discovery of potentially catastrophic
      anatomic relationships, avoiding serious complications.

PMID- 21968496
TI  - Sonographic appearances of small organizing hematomas and thrombi mimicking
      superficial soft tissue tumors.
AB  - We retrospectively reviewed 2 cases of organizing hematomas and 2 cases of
      intravascular organizing thrombi and investigated correlations between
      sonographic and pathologic findings. In all 4 cases, a well-defined hypoechoic
      heterogeneous mass with surrounding increased echogenicity was evident in the
      subcutaneous fat layer. Organizing hematomas and thrombi have sonographic
      features similar to those of benign-looking soft tissue tumors. These lesions
      should therefore be considered in the differential diagnosis of superficial soft
      tissue masses.

PMID- 21968497
TI  - Postnatal 2- and 3-dimensional sonography of the skin and nail in congenital
      autosomal recessive ichthyosis correlated with cutaneous histologic findings.

PMID- 21968498
TI  - Sonography can be useful in diagnosis of Ewing sarcoma of the calcaneus.

PMID- 21968499
TI  - Large extraluminal leiomyoma of the rectum in a patient presenting with
      decreasing stool caliber.

PMID- 21968500
TI  - Solution structure of a novel alpha-conotoxin with a distinctive loop spacing
      pattern.
AB  - alpha-Pharmacological conotoxins are among the most selective ligands of
      nicotinic acetylcholine receptors with typical cysteine frameworks. They are
      characterized by the intercysteine loop and classified into various subfamilies,
      such as alpha3/5 and alpha4/7 conotoxins. A novel alpha-conotoxin, Pu14a
      (DCPPHPVPGMHKCVCLKTC), with a distinct loop spacing pattern between cysteines was
      reported recently. Pu14a belongs to the Cys framework 14 (-C-C-C-C) family
      containing four proline residues in the loop 1 region. Similar to another
      framework 14 conotoxin Lt14a (MCPPLCKPSCTNC-NH2), Pu14a has C1-C3/C2-C4 disulfide
      linkage, and can inhibit some subtypes of nicotinic acetylcholine receptors. In
      this study, the solution structure of Pu14a was investigated using 1H nuclear
      magnetic resonance spectroscopy to understand the structure-activity relationship
      of this conotoxin. 20 converged structures of this conopeptide, with RMSD value
      of 0.77 A, were obtained based on distance constraints, dihedral angles and
      disulfide bond constraints. The three-dimensional structure of Pu14a showed
      remarkable difference from typical alpha-conotoxins because of a large
      intercysteine loop between C2 and C13, as well as a 3(10)-helix near the C
      terminal. Furthermore, four proline residues in Pu14a adopted the trans
      conformation that may correlate with the large loop configuration and the
      biological activity of this conopeptide. The distinct structural characteristics
      of Pu14a will be very useful for studying the structure-activity relationship of
      alpha-conotoxins.

PMID- 21968501
TI  - New 1,3-amino alcohols derived from enantiopure bridgehead beta
      aminobicyclo[2.2.2]oct-5-ene-2-carboxylic acids.
AB  - Constrained enantiopure bicyclic beta-amino acids derived from the asymmetric
      Diels-Alder reaction of the (R)-benzyl-4-(3-acryloyloxy-4,4-dimethyl-2
      oxopyrrolidin-1-yl)-benzoate and the 1-(benzyloxycarbonylamino)cyclohexadiene
      provide original templates for the construction of new rigid enantiopure 1,3
      amino alcohols.

PMID- 21968502
TI  - Facile synthesis of hybrid sulfonophosphinodipeptides composing of taurines and 1
      aminoalkylphosphinic acids.
AB  - Both sulfonopeptides and phosphonopeptides are important analogs of naturally
      occurring peptides and have been widely used as enzyme inhibitors and haptens for
      producing catalytic antibodies due to their tetrahedrally structural features. A
      series of hybrid sulfonophosphinodipeptides composing of taurines and 1
      aminoalkylphosphinic acids were first and conveniently synthesized in
      satisfactory to good yields via a Mannich-type reaction of N
      benzyloxycarbonylaminoalkanesulfonamides, aldehydes, and aryldichlorophosphines,
      and subsequent hydrolysis. The current method provides an efficient and direct
      synthesis of hybrid sulfonophosphinodipeptides.

PMID- 21968504
TI  - Bibliography-Editors' selection of current world literature.

PMID- 21968503
TI  - Modulators of induction of plasminogen activator inhibitor type-1 in HepG2 cells
      by transforming growth factor-beta.
AB  - OBJECTIVE: An increased expression of plasminogen activator inhibitor type-1 (PAI
      1) has been implicated in accelerating atherogenesis and coronary artery disease
      in patients with type 2 diabetes. Transforming growth factor (TGF)-beta increases
      its expression. An increased PAI-1 appears to predispose also to augmented
      fibrosis potentially contributing to negative left ventricular remodeling and
      heart failure after myocardial infarction. Diabetes is well known to induce
      oxidative stress. To elucidate molecular mechanisms underlying an increased PAI-1
      production, the effects of TGF-beta and oxidative stress implicated as agonists
      of PAI-1 synthesis were characterized with the use of human liver-derived HepG2
      cells. METHODS: PAI-1 mRNA was assayed by real-time PCR, and PAI-1 protein was
      assayed by western blotting. PAI-1 promoter (-825 -+42 bp) activity was assessed
      with the luciferase assay. The role of the 3'-untranslated region was delineated
      with the use of luciferase constructs containing the 3'-untranslated region.
      Oxidative stress was measured after loading carboxy-2,7
      dichlorodihydrofluorescein into cells. RESULTS: TGF-beta increased oxidative
      stress, which was accompanied by increases in NADPH oxidase 3 mRNA and membrane
      translocation of Rac proteins. TGF-beta-inducible increases in the PAI-1 promoter
      activity involved Smad-binding elements and a nuclear factor-kappaB-binding site.
      TGF-beta did not increase the activity of the PAI-1 mRNA 3'-untranslated region.
      TGF-beta-inducible PAI-1 expression was attenuated by simvastatin and curcumin, a
      natural polyphenol. CONCLUSION: TGF-beta can increase the expression of PAI-1
      through multiple mechanisms involving Smad and nuclear factor-kappaB pathways and
      oxidative stress. As both oxidative stress and PAI-1 production were reduced by
      simvastatin and curcumin, modulation of oxidative stress and PAI-1 production are
      attractive targets for pharmacotherapy of cardiovascular disorders associated
      with an increased PAI-1 including type 2 diabetes and its associated consequences
      including accelerated coronary artery disease and an increased fibrosis that may
      exacerbate adverse left ventricular remodeling after myocardial infarction.

PMID- 21968505
TI  - Mutation of cysteine 21 inhibits nucleophosmin/B23 oligomerization and chaperone
      activity.
AB  - Nucleophosmin (NPM/B23) is a multifunctional nucleolar protein to which both
      tumor-suppressor and oncogenic functions have been attributed. NPM/B23 has a
      variety of binding partners including ribosomes, nucleic acids, the centrosome
      and tumor suppressors such as p53 and p19ARF. These disparate functions are
      likely due to its ability to oligomerize and display molecular chaperone
      activity. In this report we identify a single amino acid residue, Cys(21), of
      nucleophosmin as important for the oligomerization and chaperone activity.
      Mutation of Cys(21) to aromatic hydrophobic residues (e.g., Phe or Try), but not
      to a conserved polar residue (e.g., Ser) inhibited the pentameric oligomerization
      of NPM/B23. However, only Phe substitution of Cys(21) drastically inhibited
      NPM/B23 chaperone activity. Interestingly, expression of Cys21Phe mutant in MCF7
      cells demonstrated that this mutant protein does not co-polymerize with
      endogenous wild-type NPM/B23 and acts as negative dominant by destabilizing the
      endogenous dimer, trimer oligomerization. Taken together, the results in this
      study identify Cys(21) as critical residue for NPM/B23 oligomerization and
      chaperone functions. In addition, Cys(21) mutant provide a strong link between
      the oligomerization and chaperone functions of NPM/B23.

PMID- 21968506
TI  - Postoperative perfluoro-N-octane tamponade for primary retinal detachment repair.
AB  - AIM: To study outcomes after using perfluoro-n-octane (PFO) as a short-term
      postoperative vitreous substitute in eyes undergoing primary vitrectomy with or
      without scleral buckling for rhegmatogenous retinal detachments with
      inferior/multiple breaks or giant retinal tears (GRTs). METHODS: Charts of 39
      eyes at 3-24 months after primary PFO retention and secondary replacement were
      retrospectively analyzed for anatomical attachment rates, visual acuity gain, and
      postoperative complications. RESULTS: Intraoperatively, 33 of 39 eyes showed >= 4
      retinal breaks, with 31 of 39 eyes having at least 1 inferior break, 10 of 39
      eyes having GRT, and 12 of 39 eyes showing preoperative proliferative
      vitreoretinopathy. All eyes showed complete anatomical retinal attachment after
      primary vitrectomy for at least 7-17 days when PFO was retained without any
      specific posturing. With sulfur hexafluoride (SF6) gas PFO exchange, 3 cases
      redetached. With perfluoropropane (C3F8) gas or silicone oil PFO exchange, no
      cases redetached, resulting in a final anatomical success rate of 92.4%. Visual
      acuity improved from 2.07 +/- 0.86 to 0.76 +/- 0.79 logarithm of the minimum
      angle of resolution (P < 0.0004) among macula-off and from 0.11 +/- 0.08 to 0.12
      +/- 0.09 logarithm of the minimum angle of resolution (P > 0.05) among macula-on
      rhegmatogenous retinal detachment eyes. Perfluoro-n-octane retention >= 10 days
      significantly increased posterior capsular opacification (28 of 39 eyes) and
      cataract extraction rates (21 of 25 eyes) without affecting the final retinal
      attachment success rate. CONCLUSION: Perfluoro-n-octane is efficacious and safe
      as a short-term vitreous substitute in primary rhegmatogenous retinal detachment
      repair cases with inferior/multiple breaks or GRTs. Perfluoro-n-octane removal
      within 10 days reduces its side effect profile considerably. The highest
      anatomical retinal reattachment rates were observed when C3F8 or silicone oil was
      exchanged for PFO.

PMID- 21968507
TI  - Relationship between baseline clinical data and microbiologic spectrum in 100
      patients with acute postcataract endophthalmitis.
AB  - PURPOSE: To correlate the initial ocular presentation with bacterial
      identification in 100 patients with acute postcataract endophthalmitis. METHODS:
      This was a prospective multicenter study. Demographic data, medical history, and
      the initial eye examination data were recorded on a standardized form. The
      relationship between bacterial identification and clinical factors at baseline
      was studied using univariate and multivariate analyses. RESULTS: One hundred
      patients were admitted to the hospital with a median delay of 6 days after
      cataract surgery. The main symptoms were loss of vision (94.9%) and pain (75.5%).
      Major clinical signs were hypopyon (72%), pupillary fibrin membrane (77.5%), and
      loss of fundus visibility (90%). Baseline factors significantly associated with
      microbiologic identification were as follows: diabetes mellitus, a shorter delay
      of onset, initial visual acuity limited to light perception, higher intraocular
      pressure, chemosis, pupillary fibrin membrane, loss of the red reflex, and
      reduced fundus visibility. As compared with other bacteria, the identification of
      Streptococcus species (n = 19) was more frequently associated with male gender,
      diabetes mellitus, initial visual acuity limited to light perception, and pain.
      The Staphylococcus aureus and Staphylococcus lugdunensis group (n = 14) differed
      from other coagulase-negative Staphylococcus groups (n = 33) in that those
      patients had greater hypopyon height. CONCLUSION: The baseline features of acute
      endophthalmitis after cataract surgery in the era of phacoemulsification are
      similar to those reported in the Endophthalmitis Vitrectomy Study 15 years ago
      and differ according to the bacterial species. The association between the
      clinical signs and the microbiologic identification suggests that initial
      characteristics other than visual acuity may be useful in identifying patients
      presumed to be infected with a virulent species.

PMID- 21968508
TI  - Type 2 idiopathic macular telangiectasia.
AB  - PURPOSE: To describe the natural course of Type 2 idiopathic macular
      telangiectasia in terms of visual outcomes, causes of visual loss, and incidence
      of subretinal neovascular membranes (SRNV). METHODS: This retrospective
      observational case series consisted of chart review of 104 outpatients (203 eyes;
      66 women, 38 men) who were diagnosed to have Type 2 idiopathic macular
      telangiectasia by clinical examination and fluorescein angiography between
      January 2000 and December 2008. Visual and anatomic outcomes were analyzed during
      a minimum follow-up of 1 year. RESULTS: The mean age of the patients was 57 years
      (range, 40-74 years). Nineteen eyes (18 patients) presented with SRNV; the number
      increased to 29 eyes (14%; 23 patients) by the final visit (mean follow-up, 31
      months). Diabetes was common (59%) though retinopathy was initially absent or
      mild to moderate in 99% patients. Mean logarithm of the minimum angle of
      resolution best-corrected visual acuity declined from 0.35 to 0.43 by the last
      visit (P < 0.0001) overall; final mean logarithm of the minimum angle of
      resolution best-corrected visual acuity was 0.61 (20/80) in the eyes with SRNV
      and 0.40 (20/50) in eyes without SRNV. The latter group started with better best
      corrected visual acuity than SRNV group and remained better at 1-year, 2-year,
      and final follow-ups (P <= 0.0002). Overall, 30 eyes (15%; 24 patients) lost >= 2
      Snellen lines, the main causes being SRNV and intraretinal pigment migration. Of
      128 eyes (including SRNV) with best-corrected visual acuity >= 20/40 at baseline,
      98 (77%) retained stable visual status; 74 (71%) patients retained best-corrected
      visual acuity of 20/40 or better at least in 1 eye. CONCLUSION: Over a follow-up
      of approximately 3 years, most eyes with Type 2 idiopathic macular telangiectasia
      starting with good vision were found to retain status quo; sight-threatening
      complications developed in a minority of eyes; most patients retained good vision
      at least in 1 eye.

PMID- 21968509
TI  - Investigation on the micelle-sensitized Ce(IV)-lornoxicam-Rh B chemiluminescence
      system and its application.
AB  - Based on the micelle synergism mechanism, a simple and sensitive flow injection
      chemiluminescence (FI-CL) method for the assay of lornoxicam was described. The
      CL signal generated from the reaction of Ce (IV) with lornoxicam in acidic
      solution was very weak, while the interfusion of sodium dodecyl benzene sulfonate
      (SDBS) resulted in a highly CL intensity. Under the optimum experimental
      conditions, the CL intensity was proportional to lornoxicam concentration over
      the range 1.0 * 10(-10)-7.3 * 10(-8) g/mL with a detection limit of 4.9 * 10(-11)
      g/mL (3sigma). The relative standard deviation for 11 replicate measurements of
      3.0 * 10(-9) g/mL of lornoxicam was 1.9%. The proposed method was successfully
      applied for the assay of lornoxicam in pharmaceuticals, human serum and urine
      with excellent recovery. The possible mechanism of CL reaction was also discussed
      briefly.

PMID- 21968510
TI  - A Survey of the Community Water Supply of some rural Riverine Communities in the
      Niger Delta region, Nigeria: Health implications and literature search for
      suitable interventions.
AB  - BACKGROUND: Water is a fundamental human need. This is the basis for target 10,
      goal 7 of the Millennium Development Goals which sets to reduce the proportion of
      people without access to safe water by half by 2015. This study assessed the
      access to safe water supply in 22 riverine communities in the Niger delta region
      of Nigeria.  MATERIALS AND METHOD: The study was carried out using a descriptive
      cross-sectional study design, with the data collected using a structured
      interviewer-administered questionnaire, field observations and focused group
      discussions. The questionnaire was administered to female heads of household, and
      used to collect information on the main source of drinking water, the time it
      took for the round trip to the main water sources, and methods used for the
      treatment of water of suspicious quality. An inventory of all the community water
      facilities in the communities was also taken, and information collected on the
      functionality of the facilities, and how they were constructed, operated and
      maintained. A sample of the water from each of the facilities was also collected
      in a sterile container for microbiological analysis.  RESULTS: A total of 456
      questionnaires were administered and retrieved. The most common source of
      drinking water was surface water (37.9%), and most (61.2%) of the water drawers
      spent less than 15 minutes to complete the round trip to the water sources. There
      were an average of 17 community water supply facilities, but only 23.8% of the
      facilities were functional during the study. Most of the functional facilities
      were being managed by community members. More than two third (67.9%) of the
      samples tested were found to contain significant numbers of Escherichia coli. 
      CONCLUSION: The communities had easy access to water supply, but most of the
      facilities were either contaminated or nonfunctional. The management of the
      facilities by members of the communities, and the promotion of point-of-use
      purification systems are hereby advocated.

PMID- 21968511
TI  - Colorectal cancer and risk of atrial fibrillation and flutter: a population-based
      case-control study.
AB  - Colorectal cancer has recently been associated with an increased atrial
      fibrillation risk, but evidence is very sparse. So, we conducted a population
      based case-control study in northern Denmark (population 1.7 million) during 1998
      2006 to estimate the atrial fibrillation/flutter risk in colorectal cancer
      patients. We identified 28,333 atrial fibrillation/flutter cases and 283,260 sex
      , age-, and county-matched population controls. We searched the databases for a
      prior colorectal cancer diagnosis, a prior cancer diagnosis other than colorectal
      cancer, and performance of surgery within 30 days prior to atrial
      fibrillation/flutter. We used conditional logistic regression to estimate the OR
      of atrial fibrillation/flutter in patients with colorectal cancer, cancers other
      than colorectal and in patient with surgery. Among cases, 0.59% (n = 168) had a
      colorectal cancer diagnosis within 90 days before their atrial
      fibrillation/flutter diagnosis, compared with 0.05% (n = 155) of controls
      (adjusted OR = 11.8; 95% CI 9.3-14.9). Beyond the first 90 days after a
      colorectal cancer diagnosis, atrial fibrillation/flutter risk was no longer
      increased. There was likewise an increased atrial fibrillation/flutter risk in
      patients diagnosed with another cancer form in the prior 90 days (OR = 7.0, 95%
      CI 6.3-7.8). Furthermore, the atrial fibrillation/flutter risk was elevated
      fivefold in patients who had undergone surgery, whether or not cancer-related. We
      therefore conclude that colorectal cancer patients are at increased atrial
      fibrillation/flutter risk exclusively in the first 90 days after cancer
      diagnosis, but to no greater an extent than are patients with other cancers. The
      performance of surgery probably plays an important role in this association.

PMID- 21968512
TI  - Kidney disease and inner ear impairment: a simpler and closer pathogenic analogy?

PMID- 21968513
TI  - Impaired functionality and homing of Fancg-deficient hematopoietic stem cells.
AB  - Fanconi anemia (FA) is a human rare genetic disorder characterized by congenital
      defects, bone marrow (BM) failure and predisposition to leukemia. The progressive
      aplastic anemia suggests a defect in the ability of hematopoietic stem cells
      (HSC) to sustain hematopoieis. We have examined the role of the nuclear FA core
      complex gene Fancg in the functionality of HSC. In Fancg-/- mice, we observed a
      decay of long-term HSC and multipotent progenitors that account for the reduction
      in the LSK compartment containing primitive hematopoietic cells. Fancg-/-
      lymphoid and myeloid progenitor cells were also affected, and myeloid progenitors
      show compromised in vitro functionality. HSC from Fancg-/- mice failed to engraft
      and to reconstitute at short and long term the hematopoiesis in a competitive
      transplantation assay. Fancg-/- LSK cells showed a loss of quiescence, an
      impaired migration in vitro in response to the chemokine CXCL12 and a defective
      homing to the BM after transplantation. Finally, the expression of several key
      genes involved in self-renewal, quiescence and migration of HSC was dysregulated
      in Fancg-deficient LSK subset. Collectively, our data reveal that Fancg should
      play a role in the regulation of physiological functions of HSC.

PMID- 21968514
TI  - Severe neuromuscular denervation of clinically relevant muscles in a mouse model
      of spinal muscular atrophy.
AB  - Spinal muscular atrophy (SMA), a motoneuron disease caused by a deficiency of the
      survival of motor neuron (SMN) protein, is characterized by motoneuron loss and
      muscle weakness. It remains unclear whether widespread loss of neuromuscular
      junctions (NMJs) is involved in SMA pathogenesis. We undertook a systematic
      examination of NMJ innervation patterns in >20 muscles in the SMNDelta7 SMA mouse
      model. We found that severe denervation (<50% fully innervated endplates) occurs
      selectively in many vulnerable axial muscles and several appendicular muscles at
      the disease end stage. Since these vulnerable muscles were located throughout the
      body and were comprised of varying muscle fiber types, it is unlikely that muscle
      location or fiber type determines susceptibility to denervation. Furthermore, we
      found a similar extent of neurofilament accumulation at NMJs in both vulnerable
      and resistant muscles before the onset of denervation, suggesting that
      neurofilament accumulation does not predict subsequent NMJ denervation. Since
      vulnerable muscles were initially innervated, but later denervated, loss of
      innervation in SMA may be attributed to defects in synapse maintenance. Finally,
      we found that denervation was amendable by trichostatin A (TSA) treatment, which
      increased innervation in clinically relevant muscles in TSA-treated SMNDelta7
      mice. Our findings suggest that neuromuscular denervation in vulnerable muscles
      is a widespread pathology in SMA, and can serve as a preparation for elucidating
      the biological basis of synapse loss, and for evaluating therapeutic efficacy.

PMID- 21968516
TI  - A phase I study of UFT-oral vinorelbine in metastatic breast cancer.
AB  - BACKGROUND: Despite current treatment options, metastatic breast cancer (MBC)
      remains essentially incurable, requiring research on new drugs or combinations to
      improve survival and quality of life. PATIENTS AND METHODS: This phase I study
      was designed to define the maximum-tolerated dose (MTD), dose-limiting toxicity
      (DLT) and recommended dose of all-oral tegafur-uracil (UFT)/folinic acid combined
      with vinorelbine as chemotherapy for MBC. Starting doses were 40 mg/m(2)/week of
      oral vinorelbine administered continuously and 250 mg/m(2)/day of UFT plus 90
      mg/day of folinic acid from day 1 to day 28, followed by a 1-week rest period.
      RESULTS: Ten patients were included. Eight were evaluable for toxicity and
      antitumor response. The second dose level was shown to be the MTD. At this dose,
      2 out of 5 patients receiving oral vinorelbine at 40 mg/m(2)/week and UFT at 300
      mg/m(2)/day developed DLT consisting of grade 3 asthenia and grade 3 nausea
      despite standard prophylaxis. Other toxicities were grade 1 diarrhea and anemia.
      There were no treatment-related deaths. CONCLUSIONS: The recommended dose for
      this combination seems to be the first dose level. A stable response was observed
      for 6 patients (average 33 weeks). This combination appears to be well-tolerated
      and offers an alternative to intravenous chemotherapy.

PMID- 21968515
TI  - Tumor suppressor or oncogene? A critical role of the human papillomavirus (HPV)
      E2 protein in cervical cancer progression.
AB  - The papillomavirus (PV) E2 proteins have been shown to exert many functions in
      the viral cycle including pivotal roles in transcriptional regulation and in
      viral DNA replication. Besides these historical roles, which rely on their
      aptitude to bind to specific DNA sequences, E2 has also been shown to modulate
      the host cells through direct protein interactions mainly through its amino
      terminal transactivation domain. We will describe here some of these new
      functions of E2 and their potential implication in the HPV-induced
      carcinogenesis. More particularly we will focus on E2-mediated modulation of the
      host cell cycle and consequences to cell transformation. In all, the HPV E2
      proteins exhibit complex functions independent of transcription that can modulate
      the host cells in concert with the viral vegetative cycle and which could be
      involved in early carcinogenesis.

PMID- 21968517
TI  - Encapsulation of cardiomyocytes in a fibrin hydrogel for cardiac tissue
      engineering.
AB  - Culturing cells in a three dimensional hydrogel environment is an important
      technique for developing constructs for tissue engineering as well as studying
      cellular responses under various culture conditions in vitro. The three
      dimensional environment more closely mimics what the cells observe in vivo due to
      the application of mechanical and chemical stimuli in all dimensions (1). Three
      dimensional hydrogels can either be made from synthetic polymers such as PEG-DA
      (2) and PLGA (3) or a number of naturally occurring proteins such as collagen
      (4), hyaluronic acid (5) or fibrin (6,7).  Hydrogels created from fibrin, a
      naturally occurring blood clotting protein, can polymerize to form a mesh that is
      part of the body's natural wound healing processes (8). Fibrin is cell-degradable
      and potentially autologous (9), making it an ideal temporary scaffold for tissue
      engineering. Here we describe in detail the isolation of neonatal cardiomyocytes
      from three day old rat pups and the preparation of the cells for encapsulation in
      fibrin hydrogel constructs for tissue engineering.  Neonatal myocytes are a
      common cell source used for in vitro studies in cardiac tissue formation and
      engineering (4).  Fibrin gel is created by mixing fibrinogen with the enzyme
      thrombin. Thrombin cleaves fibrinopeptides FpA and FpB from fibrinogen, revealing
      binding sites that interact with other monomers (10). These interactions cause
      the monomers to self-assemble into fibers that form the hydrogel mesh.  Because
      the timing of this enzymatic reaction can be adjusted by altering the ratio of
      thrombin to fibrinogen, or the ratio of calcium to thrombin, one can injection
      mold constructs with a number of different geometries (11,12).  Further we can
      generate alignment of the resulting tissue by how we constrain the gel during
      culture (13). After culturing the engineered cardiac tissue constructs for two
      weeks under static conditions, the cardiac cells have begun to remodel the
      construct and can generate a contraction force under electrical pacing conditions
      (6). As part of this protocol, we also describe methods for analyzing the tissue
      engineered myocardium after the culture period including functional analysis of
      the active force generated by the cardiac muscle construct upon electrical
      stimulation, as well as methods for determining final cell viability  (Live-Dead
      assay) and immunohistological staining to examine the expression and morphology
      of typical proteins important for contraction (Myosin Heavy Chain or MHC) and
      cellular coupling (Connexin 43 or Cx43) between myocytes.

PMID- 21968518
TI  - Iridium-catalyzed asymmetric allylation of sodium triisopropylsilanethiolate: a
      new way to form chiral thiols.
AB  - The iridium phosphoramidite complex-promoted regio- and enantioselective reaction
      of allylic carbonates with sodium triisopropylsilanethiolate produced allylic
      sulfides in 40-77% yields with up to 97 : 3 (branched : linear) and 89% ee, which
      were readily transformed into chiral thiol in 68% yield with 87% ee or disulfides
      with two chiral C-S bond centers in 40-73% yields with up to 90 : 10 dr and 99%
      ee.

PMID- 21968519
TI  - Is cerebrospinal fluid shunting in idiopathic intracranial hypertension
      worthwhile? A 10-year review.
AB  - BACKGROUND: The role of cerebrospinal fluid (CSF) diversion in treating
      idiopathic intracranial hypertension (IIH) is disputed. METHOD: We conducted a 10
      year, retrospective case note review to evaluate the effects of CSF diversion in
      IIH. Symptoms, signs and details of shunt type, complications and revisions were
      documented at baseline, 6, 12 and 24 months post-operatively. RESULTS: Fifty
      three IIH patients were shunted [predominantly lumboperitoneal (92%)]. The most
      common symptom pre-surgery was headache (96%). Post-operatively, significantly
      fewer patients experienced declining vision and visual acuity improved at 6 (p =
      0.001) and 12 months (p = 0.016). Headache continued in 68% at 6 months, 77% at
      12 months and 79% at 2 years post-operatively. Additionally, post-operative low
      pressure headache occurred in 28%. Shunt revision occurred in 51% of patients,
      with 30% requiring multiple revisions. CONCLUSION: We conclude that CSF diversion
      reduces visual decline and improves visual acuity. Unfortunately, headache
      remained in the majority of patients and low-pressure headache frequently
      complicated surgery. Over half of the patients required shunt revision with the
      majority of these requiring multiple revisions. We suggest that CSF shunting
      should be conducted as a last resort in those with otherwise untreatable, rapidly
      declining vision. Alternative treatments, such as weight reduction, may be more
      effective with less associated morbidity.

PMID- 21968520
TI  - Verrucous carcinoma of the renal pelvis with a focus of conventional squamous
      cell carcinoma.
AB  - Verrucous carcinoma (VC) is a rare variant of squamous cell carcinoma (SCC) with
      an extremely well-differentiated microscopic appearance. It is able to show
      extensive local invasion, but practically never metastasizes. VCs mostly occur in
      the oral cavity, larynx, nasal cavity, esophagus, vulva, vagina, anorectal
      region, penis and skin. VCs sometimes coexist with conventional SCCs, and in
      these instances they are associated with a higher recurrence rate than pure VCs.
      The occurrence of VC in the renal pelvis is very rare and to date only 4 cases
      have been reported. We report here a case of VC with a focus of conventional SCC
      in the renal pelvis. The patient showed fistula formation by residual tumor in
      the follow-up period.

PMID- 21968521
TI  - Dysmorphic features, cognitive disability, chronic inflammation, and
      predisposition to vascular disease in two sisters:  a new autosomal recessive
      disorder?
AB  - A 20-year-old woman presented with mental retardation and a history of stroke
      related to moyamoya disease at the age of 8 years. She had cognitive impairment
      which became more pronounced after the stroke. This patient's parents were first
      cousins and six close family relatives had strokes in their 60s or 70s. The
      patient's 16-year-old sister had learning disability, chronic muscle pain, and an
      ECG suggestive of previous hypoxemic heart injury. The two sisters had similar
      dysmorphic facial appearance including a prominent philtrum, bulbous nose, and
      severe acne. They both had increased subcutaneous tissue in their faces, whereas
      their bodies were slim. Both sisters were found to have elevated levels of
      rheumatoid factor, C-reactive protein, and erythrocyte sedimentation rate on
      repeat measurements. Partial autoimmunity screening in one of the patients was
      negative. Chromosome analysis and array comparative genomic hybridization
      analyses were also normal. Nerve conduction findings in the younger sister were
      consistent with distal, predominantly motor, demyelinating neuropathy localized
      to the lower extremities. We propose that these two sisters suffer from a new
      autosomal recessive syndrome. Carrier status for this condition may predispose to
      later onset stroke.

PMID- 21968522
TI  - Pycnodysostosis with craniosynostosis:  case report of the craniofacial and oral
      features.
AB  - Pycnodysostosis (OMIM 265800) is an uncommon hereditary disorder characterized by
      osteosclerosis of the skeleton, short stature, and bone fragility. The syndrome
      was first described by Maroteaux and Lamy (1962). Facial dysmorphology,
      hypoplasia of the mandible,dysplasia of the skull, bones with delayed closure of
      the cranial sutures, clavicular dysplasia, acroosteolysis or partial aplasia of
      the terminal phalanges, and abnormal tooth eruption have also been reported (Gelb
      et al., 1995). An autosomal recessive mode of inheritance has been also suggested
      and the locus of the disease was initially mapped to human chromosome 1q21 by
      genetic linkage (Bernard et al., 1980). Since then, several mutations on
      unrelated patients and consanguineous families have been identified in the
      cathepsin K gene (CTSK), affecting osteoclast function.Only two previous reports
      have demonstrated the presence of craniosynostosis in patients with
      pycnodysostosis(Fleming et al., 2007; Osimani et al., 2010). The purpose of this
      case report is to describe the craniofacial and dental features of a 12-year-old
      boy with pycnodysostosisand an uncommon association with craniosynosotosis.

PMID- 21968523
TI  - An optrode particle geometry to decrease response time.
AB  - A hollow 3 MUm sensing microcapsule containing chromoionophores within a 100 nm
      organosilica shell is reported. This shows a response to an ion step two orders
      of magnitude faster than 'filled' sensing particles of similar diameter.
      Incorporation of chromoionophores ETH 5294 and ETH 7061 in the capsule shell is
      shown with a t(90) response <2 s compared with >15 min for filled particles of
      similar diameters. This ultrafast geometry is also extended to dual ionophore dye
      incorporation and preliminary exploration of a FRET-based ratiometric method is
      examined to extend the pH response range, using a single excitation wavelength.

PMID- 21968524
TI  - Human leukocyte antigen antibody-incompatible renal transplantation: excellent
      medium-term outcomes with negative cytotoxic crossmatch.
AB  - BACKGROUND: Human leukocyte antigen (HLA) antibody-incompatible renal
      transplantation has been increasingly performed since 2000 but with few data on
      the medium-term outcomes. METHODS: Between 2003 and 2011, 84 patients received
      renal transplants with a pretreatment donor-specific antibody (DSA) level of more
      than 500 in a microbead assay. Seventeen patients had positive complement
      dependent cytotoxic (CDC) crossmatch (XM), 44 had negative CDC XM and positive
      flow cytometric XM, and 23 had DSA detectable by microbead only. We also reviewed
      28 patients with HLA antibodies but no DSA at transplant. DSAs were removed with
      plasmapheresis pretransplant, and patients did not routinely receive
      antithymocyte globulin posttransplant. RESULTS: Mean follow-up
      posttransplantation was 39.6 (range 2-91) months. Patient survival after the
      first year was 93.8%. Death-censored graft survival at 1, 3, and 5 years was
      97.5%, 94.2%, and 80.4%, respectively, in all DSA+ve patients, worse at 5 years
      in the CDC+ve than in the CDC-ve/DSA+ve group at 45.6% and 88.6%, respectively
      (P<0.03). Five-year graft survival in the DSA-ve group was 82.1%. Rejection
      occurred in 53.1% of DSA+ve patients in the first year compared with 22% in the
      DSA-ve patients (P<0.003). CONCLUSIONS: HLA antibody-incompatible renal
      transplantation had a high success rate if the CDC XM was negative. Further work
      is required to predict which CDC+ve XM grafts will be successful and to treat
      slowly progressive graft damage because of DSA in the first few years after
      transplantation.

PMID- 21968525
TI  - Potential limitations of presumed consent legislation.
AB  - A causal link has been proposed between presumed consent (PC) and increased
      donation; we hypothesized that too much heterogeneity exists in transplantation
      systems to support this inference. We explored variations in PC implementation
      and other potential factors affecting donation rates. In-depth interviews were
      performed with senior transplant physicians from 13 European PC countries.
      Donation was always discussed with family and would not proceed against
      objections. Country-specific, nonconsent factors were identified that could
      explain differences in donation rates. Because the process of donation in PC
      countries does not differ dramatically from the process in non-PC countries, it
      seems unlikely that PC alone increases donation rates.

PMID- 21968526
TI  - Efficacy of ultrabrief cognitive and behavioural therapy performed by psychiatric
      residents on depressed inpatients.

PMID- 21968527
TI  - Acute and delayed complications from surgery and adjuvant radiotherapy in the
      treatment of high-risk endometrial cancer.
AB  - OBJECTIVES: This retrospective study assessed the number and type of
      complications following surgery and adjuvant radiotherapy in the treatment of
      high-risk endometrial cancer. METHODS: Endometrial cancer patients who received
      surgery and postoperative radiotherapy (pelvic radiotherapy and/or vaginal
      brachytherapy) from April 1997 until October 2010 were evaluated. Short-term (<=6
      months) and long-term (>6 months) complications (e.g.,
      genitourinary/gastrointestinal complications) were comprehensively reviewed.
      RESULTS: We identified 109 high-risk endometrial cancer patients who completed
      adjuvant radiotherapy following either a total abdominal hysterectomy (TAH; n =
      53) or minimally invasive hysterectomy (MIS; n = 56). The combined impact of
      surgery and radiotherapy on complication type did not reach statistical
      significance (p > 0.05). However, surgery type and the development of a
      complication were significantly related (p < 0.001). The MIS patients developed
      complications at a more accelerated rate compared to the TAH patients (21 vs. 45
      months), although the incidence of toxicity of grade 3 or 4 was much higher in
      the TAH group. CONCLUSIONS: The impact of MIS and adjuvant radiotherapy may have
      adversely affected the development of complications compared to TAH patients who
      received adjuvant radiotherapy, although higher-grade patient toxicity was more
      prevalent in the TAH group.

PMID- 21968528
TI  - Palladium-catalyzed carbonylative coupling of benzyl chlorides with terminal
      alkynes to give 1,4-diaryl-3-butyn-2-ones and related furanones.
AB  - A general palladium-catalyzed carbonylative Sonogashira coupling of benzyl
      chlorides with terminal acetylenes has been established. Depending on the alkyne
      1,4-diaryl-3-butyn-2-ones or substituted furanones are obtained in moderate to
      good yields. Best catalytic performance is achieved applying a mixed
      Pd(PPh(3))Cl(2)/P(OPh)(3) catalyst system.

PMID- 21968529
TI  - Pericardial cyst: a rare cause of progressive and chronic cough.

PMID- 21968530
TI  - Tracking neutrophil intraluminal crawling, transendothelial migration and
      chemotaxis in tissue by intravital video microscopy.
AB  - The recruitment of circulating leukocytes from blood stream to the inflamed
      tissue is a crucial and complex process of inflammation(1,2). In the
      postcapillary venules of inflamed tissue, leukocytes initially tether and roll on
      the luminal surface of venular wall. Rolling leukocytes arrest on endothelium and
      undergo firm adhesion in response to chemokine or other chemoattractants on the
      venular surface. Many adherent leukocytes relocate from the initial site of
      adhesion to the junctional extravasation site in endothelium, a process termed
      intraluminal crawling(3). Following crawling, leukocytes move across endothelium
      (transmigration) and migrate in extravascular tissue toward the source of
      chemoattractant (chemotaxis)(4). Intravital microscopy is a powerful tool for
      visualizing leukocyte-endothelial cell interactions in vivo and revealing
      cellular and molecular mechanisms of leukocyte recruitment(2,5). In this report,
      we provide a comprehensive description of using brightfield intravital microscopy
      to visualize and determine the detailed processes of neutrophil recruitment in
      mouse cremaster muscle in response to the gradient of a neutrophil
      chemoattractant. To induce neutrophil recruitment, a small piece of agarose gel
      (~1-mm(3) size) containing neutrophil chemoattractant MIP-2 (CXCL2, a CXC
      chemokine) or WKYMVm (Trp-Lys-Tyr-Val-D-Met, a synthetic analog of bacterial
      peptide) is placed on the muscle tissue adjacent to the observed postcapillary
      venule. With time-lapsed video photography and computer software ImageJ,
      neutrophil intraluminal crawling on endothelium, neutrophil transendothelial
      migration and the migration and chemotaxis in tissue are visualized and tracked.
      This protocol allows reliable and quantitative analysis of many neutrophil
      recruitment parameters such as intraluminal crawling velocity, transmigration
      time, detachment time, migration velocity, chemotaxis velocity and chemotaxis
      index in tissue. We demonstrate that using this protocol, these neutrophil
      recruitment parameters can be stably determined and the single cell locomotion
      conveniently tracked in vivo.

PMID- 21968531
TI  - Homeostatic responses by surviving cortical pyramidal cells in neurodegenerative
      tauopathy.
AB  - Cortical neuron death is prevalent by 9 months in rTg(tau(P301L))4510 tau mutant
      mice (TG) and surviving pyramidal cells exhibit dendritic regression and spine
      loss. We used whole-cell patch-clamp recordings to investigate the impact of
      these marked structural changes on spontaneous excitatory and inhibitory
      postsynaptic currents (sEPSCs and sIPSCs) of layer 3 pyramidal cells in frontal
      cortical slices from behaviorally characterized TG and non-transgenic (NT) mice
      at this age. Frontal lobe function of TG mice was intact following a short delay
      interval but impaired following a long delay interval in an object recognition
      test, and cortical atrophy and cell loss were pronounced. Surviving TG cells had
      significantly reduced dendritic diameters, total spine density, and mushroom
      spines, yet sEPSCs were increased and sIPSCs were unchanged in frequency. Thus,
      despite significant regressive structural changes, synaptic responses were not
      reduced in TG cells, indicating that homeostatic compensatory mechanisms occur
      during progressive tauopathy. Consistent with this idea, surviving TG cells were
      more intrinsically excitable than NT cells, and exhibited sprouting of filopodia
      and axonal boutons. Moreover, the neuropil in TG mice showed an increased density
      of asymmetric synapses, although their mean size was reduced. Taken together,
      these data indicate that during progressive tauopathy, cortical pyramidal cells
      compensate for loss of afferent input by increased excitability and establishment
      of new synapses. These compensatory homeostatic mechanisms may play an important
      role in slowing the progression of neuronal network dysfunction during
      neurodegenerative tauopathies.

PMID- 21968532
TI  - TDP-43 pathological changes in early onset familial and sporadic Alzheimer's
      disease, late onset Alzheimer's disease and Down's syndrome: association with
      age, hippocampal sclerosis and clinical phenotype.
AB  - TDP-43 immunoreactive (TDP-43-ir) pathological changes were investigated in the
      temporal cortex and hippocampus of 11 patients with autosomal dominant familial
      forms of Alzheimer's disease (FAD), 169 patients with sporadic AD [85 with early
      onset disease (EOAD) (i.e before 65 years of age), and 84 with late onset after
      this age (LOAD)], 50 individuals with Down's Syndrome (DS) and 5 patients with
      primary hippocampal sclerosis (HS). TDP-43-ir pathological changes were present,
      overall, in 34/180 of AD cases. They were present in 1/11 (9%) FAD, and 9/85
      (10%) EOAD patients but were significantly more common (p = 0.003) in LOAD where
      24/84 (29%) patients showed such changes. There were no demographic differences,
      other than onset age, between AD patients with or without TDP-43-ir pathological
      changes. Double immunolabelling indicated that these TDP-43-ir inclusions were
      frequently ubiquitinated, but were only rarely AT8 (tau) immunoreactive. Only 3
      elderly DS individuals and 4/5 cases of primary HS showed similar changes.
      Overall, 21.7% of AD cases and 6% DS cases showed hippocampal sclerosis (HS).
      However, only 9% FAD cases and 16% EOAD cases showed HS, but 29% LOAD cases
      showed HS. The proportion of EOAD cases with both TDP-43 pathology and HS tended
      to be greater than those in LOAD, where nearly half of all the cases with TDP-43
      pathology did not show HS. The presence of TDP-43-ir changes in AD and DS may
      therefore be a secondary phenomenon, relating more to ageing than to AD itself.
      Nevertheless, a challenge to such an interpretation comes from the finding in AD
      of a strong relationship between TDP-43 pathology and cognitive phenotype.
      Patients with TDP-43 pathology were significantly more likely to present with an
      amnestic syndrome than those without (p < 0.0001), in keeping with pathological
      changes in medial temporal lobe structures. HS was also associated more commonly
      with an amnestic presentation (p < 0.005), but this association disappeared when
      TDP-43-positive cases were excluded from the analysis. TDP-43 may, after all, be
      integral to the pathology of AD, and to some extent determine the clinical
      phenotype present.

PMID- 21968533
TI  - Bipolar disorder type 1 and schizophrenia are accompanied by decreased density of
      parvalbumin- and somatostatin-positive interneurons in the parahippocampal
      region.
AB  - GABAergic interneurons synchronize network activities and monitor information
      flow. Post-mortem studies have reported decreased densities of cortical
      interneurons in schizophrenia (SZ) and bipolar disorder (BPD). The entorhinal
      cortex (EC) and the adjacent subicular regions are a hub for integration of
      hippocampal and cortical information, a process that is disrupted in SZ. Here we
      contrast and compare the density of interneuron populations in the caudal EC and
      subicular regions in BPD type I (BPD-I), SZ, and normal control (NC) subjects.
      Post-mortem human parahippocampal specimens of 13 BPD-I, 11 SZ and 17 NC subjects
      were used to examine the numerical density of parvalbumin-, somatostatin- or
      calbindin-positive interneurons. We observed a reduction in the numerical density
      of parvalbumin- and somatostatin-positive interneurons in the caudal EC and
      parasubiculum in BPD-I and SZ, but no change in the subiculum. Calbindin-positive
      interneuron densities were normal in all brain areas examined. The profile of
      decreased density was strikingly similar in BPD-I and SZ. Our results demonstrate
      a specific reduction of parvalbumin- and somatostatin-positive interneurons in
      the parahippocampal region in BPD-I and SZ, likely disrupting synchronization and
      integration of cortico-hippocampal circuits.

PMID- 21968534
TI  - Synthesis of ent-kaurane diterpene monoglycosides.
AB  - Synthesis of two ent-kaurane diterpene glycosides, steviol 19-O-beta-D
      glucopyranosiduronic acid (steviol glucuronide, 5), and 13-hydroxy ent-kaur-16-en
      19-oic acid-beta-D-glucopyranosyl ester (7) has been achieved from a common
      starting material, steviol, using phase transfer catalyst. Also, synthesis of an
      additional 17-nor-ent-kaurane glycoside, namely 13-methyl-16-oxo-17-nor-ent
      kauran-19-oic acid-beta-D-glucopyranosyl ester (10) was performed using the
      starting material isosteviol and similar synthetic methodology. Synthesis of all
      three steviol glycosides was performed using straightforward chemistry and their
      structures were characterized on the basis of 1D and 2D NMR as well as mass
      spectral (MS) data.

PMID- 21968535
TI  - Mastitis and its impact on structure and function in the ruminant mammary gland.
AB  - It is a given in biology that structure and function go hand-in-hand. At the
      level of the mammary alveoli, copious milk production depends on the
      proliferation of mammary epithelial cells and the biochemical and structural
      differentiation of these cells after parturition. For example, data from
      quantitative structural studies demonstrate that differences in milk production
      between beef and dairy cows correspond with a relative failure of alveolar cell
      differentiation in cattle not specifically selected for milk yield. It is likely,
      but not proven, that production differences within or between dairy breeds are
      also determined by differences in the capacity of alveolar cells to differentiate
      or to maintain an adequate state of differentiation. These observations strongly
      support the belief that insults from mastitis that lead to losses in mammary
      function are directly related to disruption of alveolar cell integrity, sloughing
      of cells, induced apoptosis, and increased appearance of poorly-differentiated
      cells. Ironically, reduced milk production in cases of subclinical mastitis, is
      also associated with increases in milk somatic cell count. Thus the elevated
      neutrophil migration evoked to fight inflammation can inadvertently rendered
      alveolar epithelial cells non-secretory. A challenge to future researchers will
      be to devise mastitis treatments and therapies that prevent and/or repair damage
      to alveolar structure and maximize subsequent secretory cell differentiation.

PMID- 21968536
TI  - Functional adaptations of the transcriptome to mastitis-causing pathogens: the
      mammary gland and beyond.
AB  - Application of microarrays to the study of intramammary infections in recent
      years has provided a wealth of fundamental information on the transcriptomics
      adaptation of tissue/cells to the disease. Due to its heavy toll on productivity
      and health of the animal, in vivo and in vitro transcriptomics works involving
      different mastitis-causing pathogens have been conducted on the mammary gland,
      primarily on livestock species such as cow and sheep, with few studies in non
      ruminants. However, the response to an infectious challenge originating in the
      mammary gland elicits systemic responses in the animal and encompasses tissues
      such as liver and immune cells in the circulation, with also potential effects on
      other tissues such as adipose. The susceptibility of the animal to develop
      mastitis likely is affected by factors beyond the mammary gland, e.g. negative
      energy balance as it occurs around parturition. Objectives of this review are to
      discuss the use of systems biology concepts for the holistic study of animal
      responses to intramammary infection; providing an update of recent work using
      transcriptomics to study mammary and peripheral tissue (i.e. liver) as well as
      neutrophils and macrophage responses to mastitis-causing pathogens; discuss the
      effect of negative energy balance on mastitis predisposition; and analyze the
      bovine and murine mammary innate-immune responses during lactation and involution
      using a novel functional analysis approach to uncover potential predisposing
      factors to mastitis throughout an animal's productive life.

PMID- 21968537
TI  - Targeting mucosal immunity in the battle to develop a mastitis vaccine.
AB  - The mucosal immune system encounters antigens that enhance and suppress immune
      function, and serves as a selective barrier against invading pathogens. The
      mammary gland not only encounters antigens but also produces a nutrient evolved
      to protect and enhance mucosal development in the neonate. Efforts to manipulate
      antibody concentrations in milk to prevent mastitis, an infection of the mammary
      gland, have been hampered both by complexity and variation in target pathogens
      and limited knowledge of cellular immunity in the gland. Successful vaccination
      strategies must overcome the natural processes that regulate types and
      concentrations of milk antibodies for neonatal development, and enhance cellular
      immunity. Furthermore, the need to overcome dampening of immunity caused by non
      pathogenic encounters to successfully prevent establishment of infection is an
      additional obstacle in vaccine development at mucosal sites. A significant
      mastitis pathogen, Staphylococcus aureus, not only resides as a normal flora on a
      multitude of species, but also causes clinical disease with limited treatment
      options. Using the bovine model of S. aureus mastitis, researchers can decipher
      the role of antigen selection and presentation by mammary dendritic cells,
      enhance development of central and effector memory function, and subsequently
      target specific memory cells to the mammary gland for successful vaccine
      development. This brief review provides an overview of adaptive immunity,
      previous vaccine efforts, current immunological findings relevant to enhancing
      immune memory, and research technologies that show promise in directing future
      vaccine efforts to enhance mammary gland immunity and prevent mastitis.

PMID- 21968539
TI  - Responses of Lyngbya wollei to exposures of copper-based algaecides: the critical
      burden concept.
AB  - The formulation of a specific algaecide can greatly influence the
      bioavailability, uptake, and consequent control of the targeted alga. In this
      research, three copper-based algaecide formulations were evaluated in terms of
      copper sorption to a specific problematic alga and amount of copper required to
      achieve control. The objectives of this study were (1) to compare the masses of
      copper required to achieve control of Lyngbya wollei using the algaecide
      formulations Algimycin-PWF, Clearigate, and copper sulfate pentahydrate in
      laboratory toxicity experiments; (2) to relate the responses of L. wollei to the
      masses of copper adsorbed and absorbed (i.e., dose) as well as the concentrations
      of copper in the exposure water; and (3) to discern the relation between the mass
      of copper required to achieve control of a certain mass of L. wollei among
      different algaecide formulations. The critical burden of copper (i.e., threshold
      algaecide concentration that must be absorbed or adsorbed to achieve control) for
      L. wollei averaged 3.3 and 1.9 mg Cu/g algae for Algimycin-PWF and Clearigate,
      respectively, in experiments with a series of aqueous copper concentrations,
      water volumes, and masses of algae. With reasonable exposures in these
      experiments, control was not achieved with single applications of copper sulfate
      despite copper sorption >13 mg Cu/g algae in one experiment. Factors governing
      the critical burden of copper required for control of problematic cyanobacteria
      include algaecide formulation and concentration, volume of water, and mass of
      algae. By measuring the critical burden of copper from an algaecide formulation
      necessary to achieve control of the targeted algae, selection of an effective
      product and treatment rate can be calculated at a given field site.

PMID- 21968540
TI  - Interferon-beta, but not tumor necrosis factor-alpha, production in response to
      poly I:C is maintained despite exhaustive exercise in mice.
AB  - It remains unclear whether immune response to viral infection is inhibited by
      severe exercise. We determined whether exhaustive exercise inhibits interferon
      (IFN)-beta and tumor necrosis factor (TNF)-alpha production after injection of
      synthetic double-stranded (ds) RNAs, a polyriboinosinic polyribocytidylic acid
      (poly I:C), as viral infection model. Male C3H/HeN mice, which were divided into
      exhaustive-exercised and non-exercised groups, were injected with poly I:C (5
      mg/kg). Although TNF-alpha in response to poly I:C was significantly inhibited by
      exhaustive exercise, IFN-beta was no different in both groups. In in-vitro
      experiments, catecholamines inhibited poly I:C-induced TNF-alpha, but not IFN
      beta, production in macrophages. These results suggest that anti-virus cytokine
      IFN-beta in response to poly I:C might be maintained despite severe stressful
      exercise.

PMID- 21968541
TI  - Penile amputation and scrotal urethrostomy in 18 dogs.
AB  - The objective of this study was to report the signalment, indications for
      surgery, postoperative complications and outcome in dogs undergoing penile
      amputation and scrotal urethrostomy. Medical records of three surgical referral
      facilities were reviewed for dogs undergoing penile amputation and scrotal
      urethrostomy between January 2003 and July 2010. Data collected included
      signalment, presenting signs, indication for penile amputation, surgical
      technique, postoperative complications and long-term outcome. Eighteen dogs were
      included in the study. Indications for surgery were treatment of neoplasia (n=6),
      external or unknown penile trauma (n=4), penile trauma or necrosis associated
      with urethral obstruction with calculi (n=3), priapism (n=4) and balanoposthitis
      (n=1). All dogs suffered mild postoperative haemorrhage (posturination and/or
      spontaneous) from the urethrostomy stoma for up to 21 days (mean 5.5 days). Four
      dogs had minor complications recorded at suture removal (minor dehiscence (n=1),
      mild bruising and swelling around the urethrostomy site and mild haemorrhage at
      suture removal (n=2), and granulation at the edge of stoma (n=1)). One dog had a
      major complication (wound dehiscence and subsequent stricture of the stoma). Long
      term outcome was excellent in all dogs with non-neoplastic disease. Local tumour
      recurrence and/or metastatic disease occurred within five to 12 months of surgery
      in two dogs undergoing penile amputation for the treatment of neoplasia. Both
      dogs were euthanased.

PMID- 21968542
TI  - Bleeding time in healthy dogs sedated with morphine and medetomidine.

PMID- 21968538
TI  - Molecular epidemiology of mastitis pathogens of dairy cattle and comparative
      relevance to humans.
AB  - Mastitis, inflammation of the mammary gland, can be caused by a wide range of
      organisms, including gram-negative and gram-positive bacteria, mycoplasmas and
      algae. Many microbial species that are common causes of bovine mastitis, such as
      Escherichia coli, Klebsiella pneumoniae, Streptococcus agalactiae and
      Staphylococcus aureus also occur as commensals or pathogens of humans whereas
      other causative species, such as Streptococcus uberis, Streptococcus dysgalactiae
      subsp. dysgalactiae or Staphylococcus chromogenes, are almost exclusively found
      in animals. A wide range of molecular typing methods have been used in the past
      two decades to investigate the epidemiology of bovine mastitis at the subspecies
      level. These include comparative typing methods that are based on electrophoretic
      banding patterns, library typing methods that are based on the sequence of
      selected genes, virulence gene arrays and whole genome sequencing projects. The
      strain distribution of mastitis pathogens has been investigated within individual
      animals and across animals, herds, countries and host species, with consideration
      of the mammary gland, other animal or human body sites, and environmental
      sources. Molecular epidemiological studies have contributed considerably to our
      understanding of sources, transmission routes, and prognosis for many bovine
      mastitis pathogens and to our understanding of mechanisms of host-adaptation and
      disease causation. In this review, we summarize knowledge gleaned from two
      decades of molecular epidemiological studies of mastitis pathogens in dairy
      cattle and discuss aspects of comparative relevance to human medicine.

PMID- 21968543
TI  - Survivorship care planning after the institute of medicine recommendations: how
      are we faring?
AB  - INTRODUCTION: This study evaluates the concordance of treatment summaries (TSs)
      and survivorship care plans (SCPs) delivered to breast cancer survivors within
      the LIVESTRONGTM Network of Survivorship Centers of Excellence with Institute of
      Medicine (IOM) recommendations and describes additional structure/process
      variables. METHOD: Seven NCI-designated comprehensive cancer centers and six
      community-based centers participated. TS/SCPs for 65 patients were rated against
      IOM recommendations using a study-derived checklist, and surveys were
      administered to better understand the structure and process of delivering
      TSs/SCPs. RESULTS: On average, fewer than half of IOM content recommendations
      were met for TSs (M = 46%) and less than two thirds for SCPs (M = 59%). No sites
      achieved >=75% overall concordance with IOM recommendations for TSs and only two
      of 13 met this criterion for SCPs. Content domain scores across sites varied
      widely, as did the number of sites addressing domain content with >=75%
      concordance. Nonetheless, resources required for document preparation and
      delivery were substantial. DISCUSSION: Gaps in concordance with IOM
      recommendations exist even in dedicated survivorship centers. A substantial time
      burden was also noted. Further research is needed to determine which
      informational elements are essential, to develop and test strategies for
      improving efficiency and reach, and to determine if outcomes of survivorship care
      planning warrant the resources required in their preparation and delivery.
      IMPLICATIONS FOR SURVIVORS: TSs and SCPs have been recommended for all cancer
      survivors. Essential elements must be determined, approaches made more efficient,
      outcome improvements demonstrated, and cost-benefit analyses determined before
      survivors should expect widespread implementation of this recommendation for
      survivorship care.

PMID- 21968544
TI  - Interleukin-21 promotes osteoclastogenesis in humans with rheumatoid arthritis
      and in mice with collagen-induced arthritis.
AB  - OBJECTIVE: Bone destruction is a critical pathology involved in the functional
      disability caused by rheumatoid arthritis (RA). Osteoclasts, which are
      specialized bone-resorbing cells regulated by cytokines such as RANKL, are
      implicated in bone destruction in RA. The aim of this study was to determine
      whether interleukin-21 (IL-21), a potent immunomodulatory 4-alpha-helical bundle
      type 1 cytokine, has osteoclastogenic activity in patients with RA and in mice
      with collagen-induced arthritis (CIA). METHODS: The expression of IL-21 in
      synovial tissue was examined using immunohistochemistry. The concentrations of IL
      21 in serum and synovial fluid were determined by enzyme-linked immunosorbent
      assay. The levels of RANKL and osteoclastogenic markers were measured using real
      time polymerase chain reaction. CD14+ monocytes from patients with RA or mouse
      bone marrow cells were cocultured with fibroblast-like synoviocytes (FLS) from
      patients with RA or CD4+ T cells from mice with CIA in the presence of IL-21 and
      subsequently stained for tartrate-resistant acid phosphatase activity to
      determine osteoclast formation. RESULTS: IL-21 was up-regulated in the synovium,
      synovial fluid, and serum of patients with RA and in the synovium and serum of
      mice with CIA. IL-21 induced RANKL expression in mixed joint cells and CD4+ T
      cells from mice with CIA and in CD4+ T cells and FLS from patients with RA.
      Moreover, IL-21 enhanced in vitro osteoclastogenesis without the presence of
      RANKL-providing cells and by inducing RANKL expression in CD4+ T cells and FLS.
      CONCLUSION: Our data suggest that IL-21 promotes osteoclastogenesis in RA. We
      believe that therapeutic strategies targeting IL-21 might be effective for the
      treatment of patients with RA, especially in preventing bone destruction.

PMID- 21968545
TI  - The effect of obesity on regadenoson-induced myocardial hyperemia: a quantitative
      magnetic resonance imaging study.
AB  - The A2(A) receptor agonist, regadenoson, is increasingly used as a vasodilator
      during nuclear myocardial perfusion imaging. Regadenoson is administered as a
      single, fixed dose. Given the frequency of obesity in patients with symptoms of
      heart disease, it is important to know whether the fixed dose of regadenoson
      produces maximal coronary hyperemia in subjects of widely varying body size.
      Thirty subjects (12 female, 18 male, mean BMI 30.3 +/- 6.5, range 19.6-46.6) were
      imaged on a 3T magnetic resonance scanner. Imaging with a saturation recovery
      radial turboFLASH sequence was done first at rest, then during adenosine infusion
      (140 MUg/kg/min) and 30 min later with regadenoson (0.4 mg/5 ml bolus). A 5 cc/s
      injection of Gd-BOPTA was used for each perfusion sequence, with doses of 0.02,
      0.03 and 0.03 mmol/kg, respectively. Analysis of the upslope of myocardial time
      intensity curves and quantitative processing to obtain myocardial perfusion
      reserve (MPR) values were performed for each vasodilator. The tissue upslopes for
      adenosine and regadenoson matched closely (y = 1.1x + 0.03, r = 0.9). Mean MPR
      was 2.3 +/- 0.6 for adenosine and 2.4 +/- 0.9 for regadenoson (p = 0.14). There
      was good agreement between MPR measured with adenosine and regadenoson (y = 1.1x 
      0.06, r = 0.7). The MPR values measured with both agents tended to be lower as
      BMI increased. There were no complications during administration of either agent.
      Regadenoson produced fewer side effects. Fixed dose regadenoson and weight
      adjusted adenosine produce similar measures of MPR in patients with a wide range
      of body sizes. Regadenoson is a potentially useful vasodilator for stress MRI
      studies.

PMID- 21968546
TI  - Contrast material injection protocol with the flow rate adjusted to the heart
      rate for dual source CT coronary angiography.
AB  - To investigate the effect on coronary arterial attenuations of contrast material
      flow rate adjusted to a patient's heart rate during dual source CT coronary
      angiography (DSCT-CCTA). A total of 296 consecutive patients (mean age: 58.7
      years) undergoing DSCT-CCTA without previous coronary stent placement, bypass
      surgery, congenital or valvular heart disease were included. The image
      acquisition protocol was standardized (120 kV, 380 mAs) and retrospective
      electrocardiograph (ECG) gating was used. Patients were randomly assigned to one
      of three groups [flow rate: G1: dosage/16, G2: dosage/(scan time +8), G3: fixed
      flow rate]. The groups were compared with respect to the attenuations of the
      ascending aorta (AA) above coronary ostia, the left main coronary artery (LM),
      the proximal right coronary artery (RCA), the left anterior descending artery
      (LAD), the left circumflex artery (LCX), and the contrast to noise ratio of the
      LM (LM(CNR)) and the proximal RCA (RCA(CNR)). Correlations between heart rate and
      attenuation of the coronary arteries were evaluated in three groups with linear
      regression. There was no significant difference in the three groups among the
      mean attenuations of AA (P = 0.141), LM (P = 0.068), RCA (P = 0.284), LM(CNR) (P
      = 0.598) and RCA(CNR) (P = 0.546). The attenuations of the LAD and the LCX in
      group 1 were slightly higher than those in group 2 and 3 (P < 0.05). In group 1,
      the attenuations of the AA (P < 0.01), LM (P < 0.01), RCA (P < 0.01), LAD (P =
      0.02) and LCX (P < 0.01) decreased, respectively, with an increasing heart rate.
      A similar finding was detected in group 3 (AA: P < 0.01, LM: P < 0.01, RCA: P <
      0.01, LAD: P < 0.01 and LCX: P < 0.01). In contrast, the attenuations of the AA
      (P = 0.55), LM (P = 0.27), RCA (P = 0.77), LAD (P = 0.22) and LCX (P = 0.74) had
      no significant correlation with heart rate in group 2. In all three groups,
      LM(CNR) (P = 0.77, 0.69 and 0.73 respectively) and RCA(CNR) (P = 0.75, 0.39 and
      0.61 respectively) had no significant correlation with heart rate. Contrast
      material flow rate adjusted to heart rate can diminish the influence of heart
      rate on attenuations of the coronary arteries in DSCT-CCTA.

PMID- 21968547
TI  - Inflammation and axon regeneration.
AB  - PURPOSE OF REVIEW: The inflammatory response that accompanies neural injury
      involves multiple cell types and effector molecules with both positive and
      negative effects. Inflammation is essential for normal regeneration in the
      peripheral nervous system, and here we review evidence that augmenting
      inflammation can enhance regeneration in areas of the central nervous system in
      which it normally does not occur. RECENT FINDINGS: Within the spinal cord,
      inflammation enables transplanted sensory neurons to regenerate lengthy axons and
      enhances the ability of a trophic factor to promote corticospinal tract
      sprouting. Induction of inflammation in the eye supports survival of retinal
      ganglion cells and enables them to regenerate injured axons through the optic
      nerve. These effects are linked to an atypical trophic factor, oncomodulin, along
      with other, better known molecules. Induction of inflammation within dorsal root
      ganglia, when combined with other treatments, enables peripheral sensory neurons
      to regenerate axons into the spinal cord. However, inflammation also has negative
      effects that impede recovery. SUMMARY: In light of the importance of inflammation
      for neural repair, it is important to identify the specific cell types and
      molecules responsible for the positive and negative effects of inflammation and
      to develop treatments that tip the balance to favor repair.

PMID- 21968548
TI  - Modulation of motor performance and motor learning by transcranial direct current
      stimulation.
AB  - PURPOSE OF REVIEW: Transcranial direct current stimulation (tDCS) has shown
      preliminary success in improving motor performance and motor learning in healthy
      individuals, and restitution of motor deficits in stroke patients. This brief
      review highlights some recent work. RECENT FINDINGS: Within the past years,
      behavioural studies have confirmed and specified the timing and polarity specific
      effects of tDCS on motor skill learning and motor adaptation. There is strong
      evidence that timely co-application of (hand/arm) training and anodal tDCS to the
      contralateral M1 can improve motor learning. Improvements in motor function as
      measured by clinical scores have been described for combined tDCS and training in
      stroke patients. For this purpose, electrode montages have been modified with
      respect to interhemispheric imbalance after brain injury. Cathodal tDCS applied
      to the unlesioned M1 or bihemispheric M1 stimulation appears to be well tolerated
      and useful to induce improvements in motor function. Mechanistic studies in
      humans and animals are discussed with regard to physiological motor learning.
      SUMMARY: tDCS is well tolerated, easy to use and capable of inducing lasting
      improvements in motor function. This method holds promise for the rehabilitation
      of motor disabilities, although acute studies in patients with brain injury are
      so far lacking.

PMID- 21968549
TI  - Geriatric neuro-oncology:  from mythology to biology.
AB  - PURPOSE OF REVIEW: Age has remained one of the most important determinants of
      risk for the development of certain brain tumors, of benefit from and tolerance
      of brain tumor treatment, and overall outcome. Regarding these three aspects,
      there are major differences across the spectrum of primary brain tumors depending
      on specific histology. Here, we review recent advances in understanding the
      biological basis of the prognostic marker 'age' in neuro-oncology. RECENT
      FINDINGS: Contemporary population-based studies confirm the strong prognostic
      impact of age in many brain tumors. Elderly patients continue to be treated less
      aggressively than younger patients with the same tumors. However, biological
      factors may contribute to the negative prognostic impact of age. For instance,
      among gliomas, mutations of the isocitrate dehydrogenase genes, which are
      prognostically favorable, are much more common in younger patients. Moreover,
      complete responses defined by neuroimaging were much less durable in elderly as
      opposed to younger patients with primary central nervous system lymphoma in the
      German Primary Central Nervous System Lymphoma Study Group trial. SUMMARY: A
      combination of age-adapted patterns of care and treatment-independent, tumor
      intrinsic factors contributes to the poorer outcome of elderly patients with
      brain tumors. These factors need to be better distinguished and understood in
      order to improve outcome in elderly brain tumor patients.

PMID- 21968550
TI  - Traumatic brain injury:  relation to executive dysfunction and the frontal lobes.
AB  - PURPOSE OF REVIEW: This review examines the applicability of a framework of
      frontal lobe functioning to understand the sequelae of traumatic brain injury
      (TBI). RECENT FINDINGS: TBI research illustrates the need for improved
      phenotyping of TBI outcome. The functions of the frontal lobes are divisible into
      four distinct anatomically discrete categories: executive functions, speed of
      processing, personality changes, and problems with empathy and social cognition.
      Research on the outcome after TBI demonstrates several different types of
      impairment that map onto this framework. SUMMARY: TBI predominantly causes damage
      to the frontal/temporal regions, regardless of the pathophysiology. Limiting the
      spotlight to the frontal lobes, a model is presented describing four separate
      general categories of functions within the frontal lobes, with specific types of
      processes within each category. A selective review of TBI literature supports the
      importance of evaluating TBI patients with this framework in mind. In addition,
      there is growing evidence that rehabilitation of TBI patients must consider this
      broader approach to direct rehabilitation efforts and improve outcome.

PMID- 21968551
TI  - Primary central nervous system lymphoma:  is there still a role for radiotherapy?
AB  - PURPOSE OF REVIEW: Adding high-dose methotrexate to whole-brain radiotherapy
      improves survival in primary central nervous system lymphoma. However, the high
      neurotoxicity rates observed, especially in the elderly, raised interest in
      exploring other alternatives such as reduced-dose radiotherapy and chemotherapy
      only treatments. RECENT FINDINGS: Phase II studies suggested that omitting
      radiotherapy decreases progression-free survival (PFS) but not overall survival.
      A randomized phase III trial testing chemotherapy with/without radiation found
      similar results. However, interpretation of that trial has been difficult because
      of the chemotherapy regimen used (methotrexate with/without ifosfamide),
      intrinsic methodological problems and lack of neuropsychological evaluation. It
      also remains unclear whether chemotherapy-only treatments could ultimately result
      in worse cognitive outcomes in comparison with combined chemotherapy and
      radiotherapy because the higher rates of relapses could result in additional
      neurotoxicity from salvage treatments and brain damage by relapsing tumor. Given
      differences in relapses and neurotoxicity rates according to age, it is also
      unclear how results apply to younger versus older patients. SUMMARY: Given the
      lack of better data, omitting radiotherapy currently seems a justifiable choice
      in routine practice, particularly in the elderly, but the question remains
      unsettled. Ongoing studies are investigating other consolidation options,
      including reduced-dose radiotherapy and high-dose chemotherapy with stem-cell
      rescue, aiming at improving disease control and decreasing neurotoxicity.

PMID- 21968553
TI  - Photoaffinity labeling of the multidrug resistance protein 2 (ABCC2/cMOAT) with a
      photoreactive analog of LTC(4).
AB  - Several studies have shown that the multidrug resistant protein MRP2 mediates the
      transport of chemotherapeutic drugs and normal cell metabolites, including
      Leukotriene C (LTC(4)); however direct binding of the LTC(4) to MRP2 has not been
      demonstrated. In this study, a photoreactive analog of LTC(4) (IAALTC(4)) was
      used to demonstrate its direct binding to MRP2. Our results show specific
      photoaffinity labeling of MRP2 with IAALTC(4) in plasma membranes from
      MDCKII(MRP2) cells. The photoaffinity labeling signal of MRP2 with IAALTC(4) was
      much lower than that of MRP1, consistent with previous studies whereby the
      measured K(m) values of MRP1 and MRP2 for LTC(4) were 1 MUM and 0.1 MUM LTC(4),
      respectively. Competition of IAALTC(4) photoaffinity labeling to MRP2 with MK571,
      a well characterized inhibitor of MRP2 function, showed ~75% reduction in binding
      in the presence of 50 MUM excess MK571. Interestingly, unmodified LTC(4) enhanced
      the photoaffinity labeling of IAALTC(4) to MRP2, whereas excess GSH and Quercetin
      had no significant effect. Mild tryptic digestion of photoaffinity labeled MRP2
      revealed several photoaffinity labeled peptides that localized the IAALTC(4)
      binding to a 15 kDa amino acid sequence that contains transmembrane 16 and 17.
      Together these results provide the first demonstration of direct LTC(4) binding
      to MRP2.

PMID- 21968552
TI  - Correlation of cone beam computed tomography (CBCT) findings in the maxillary
      sinus with dental diagnoses: a retrospective cross-sectional study.
AB  - This study was conducted to assess the coincidence of mucosal hyperplasia in the
      maxillary sinus and related clinical diagnoses of posterior maxillary teeth found
      in cone beam computed tomography (CBCT) scans. A total of 204 patients who
      underwent CBCT examinations between 2006 and 2008 were evaluated retrospectively.
      Clinical and CBCT findings were correlated using patient records. Absolute
      frequencies, odds ratios (OR), and 95% confidence intervals (95% CI) were
      calculated for statistical evaluations. There was a pronounced association
      between periodontitis and radiological signs of sinusitis. Basal mucosal wall
      thickening was more likely in patients with decayed and non-vital teeth compared
      to patients with sound teeth (OR = 5.2; 95% CI = 1.2-23.1). Basal mucosal wall
      thickening was also more likely than total mucosal thickening (OR = 10.4; 95% CI
      = 2.6-42.2). Patients with decayed and endodontically treated teeth were more
      likely to exhibit involvement of the basal wall (OR = 9.2; 95% CI = 3.3-25.2)
      than were patients with healthy teeth. CBCT examinations revealed a correlation
      between basal mucosal thickening in the maxillary sinus and decayed posterior
      maxillary teeth or periodontitis. Chronic symptoms involving the sinuses are one
      of the most common reasons for patients to consult physicians. One reason for
      chronic orofacial pain is the prevalence of undiagnosed sinus conditions.

PMID- 21968554
TI  - Silencing receptor EphA2 induces apoptosis and attenuates tumor growth in
      malignant mesothelioma.
AB  - Receptor EphA2 over-expression is associated with the aggressive nature of growth
      in malignant mesothelioma (MM) and silencing EphA2 with interference RNA
      suppressed MM proliferation. The mechanisms associated with targeting the EphA2
      gene in MM were not clear. We sought to determine whether silencing EphA2 induces
      apoptosis in MM cells by either extrinsic or intrinsic pathways. The receptor
      EphA2 signaling pathway may provide attractive therapeutic strategy for MM.
      Apoptosis was determined by Cell Death ELISA in MM Cells transfected with siRNA
      EphA2 and control siRNA. The gene expression profile of apoptosis pathways were
      analyzed by GEArray. Selected genes were further studied by quantitative PCR,
      Western analysis, and immunofluorescence. Caspases activities were measured by
      fluorescence spectrometer. Silencing EphA2 expression induced apoptosis in MMC.
      Apoptosis was characterized by FADD expression, activated caspase-8, caspase-3
      and induction of Bax, Bak, and Bid as revealed by GEArray and protein
      fractionation assays. The expression of FADD, Bid, caspase-8, cytochrome-c and
      apaf-1 were significantly higher in the cytosolic fractions of EphA2-siRNA
      transfected cells. Furthermore, blocking the expression of caspase-8 by an
      inhibitor blunted FADD expression, indicating that caspase-8 is implicated in
      EphA2-siRNA induced apoptosis in MMC. Our data indicates that targeting the EphA2
      gene by siRNA induced both extrinsic and intrinsic apoptotic pathways in MM
      Cells. Receptor EphA2 inhibition may be an effective approach for inhibiting MM
      growth and a promising direction for MM therapy.

PMID- 21968555
TI  - Therapist judgment of defense styles and therapeutic technique related to outcome
      in psychodynamic psychotherapy for depression.

PMID- 21968556
TI  - Aphasia centers: a growing trend in North America.

PMID- 21968557
TI  - Aphasia centers in North America: a survey.
AB  - There is a growing trend toward dedicated programs designed to improve the lives
      of people with aphasia and their families. We are referring to these programs
      collectively as "aphasia centers." These programs purportedly differ from more
      traditional medically based aphasia rehabilitation. However, there is no
      directory of aphasia centers and no definition of what constitutes such a
      program. Therefore, an online survey was designed to identify and describe
      aphasia centers in the United States and Canada. A 37-question survey was posted
      online via SurveyMonkey. An introductory letter was distributed by electronic
      mail to a listserv and mailing lists of programs associated with aphasia.
      Potential respondents who considered themselves an aphasia center were asked to
      complete the survey. A total of 33 survey responses were analyzed, and
      descriptive data were compiled resulting in a description of the following
      aspects of aphasia centers: demographic information, mission, admission and
      discharge policies, assessment practices, program logistics, staffing patterns,
      marketing, funding, and services offered. In addition, a qualitative analysis of
      written text responses revealed the following key themes that appear to
      characterize the responding programs: services that differ from traditional
      aphasia rehabilitation; a sense of community; a holistic focus on quality of
      life, psychosocial well-being, participation, and social support; the centrality
      of group interaction; and variety/intensity of services.

PMID- 21968558
TI  - A-FROM in action at the Aphasia Institute.
AB  - Aphasia centers are in an excellent position to contribute to the broad
      definition of health by the World Health Organization: the ability to live life
      to its full potential. An expansion of this definition by the World Health
      Organization International Classification of Functioning, Disability and Health
      (ICF) forms the basis for a user-friendly and ICF-compatible framework for
      planning interventions that ensure maximum real-life outcome and impact for
      people with aphasia and their families. This article describes Living with
      Aphasia: Framework for Outcome Measurement and its practical application to
      aphasia centers in the areas of direct service, outcome measurement, and advocacy
      and awareness. Examples will be drawn from the Aphasia Institute in Toronto. A
      case will be made for all aphasia centers to use the ICF or an adaptation of it
      to further the work of this sector and strengthen its credibility.

PMID- 21968559
TI  - "Waiting on the words": procedures and outcomes of a drama class for individuals
      with aphasia.
AB  - Drama therapy offers an authentic medium through which people with aphasia can
      interact and share their experiences. We describe the rationale and procedures of
      a drama class, informed by the principles and practices of drama therapy, in
      which individuals with chronic aphasia conceptualized, wrote, and produced a play
      addressing their experiences of having, living with, and coping with the effects
      of aphasia. Sessions were cofacilitated by a speech-language pathologist and a
      drama therapist. We describe the drama activities and techniques in each of four
      distinct stages of a drama therapy process through which the group transitioned.
      We also summarize patient-reported outcomes of a representational group of seven
      participants. Subscales of the Burden of Stroke Scale and the Communication
      Confidence Rating Scale for Aphasia were administered before and after
      participation in the 18-week class. Means, standard deviations, and effect sizes
      were computed. Results indicated perceived improvements in both communication and
      mood.

PMID- 21968560
TI  - Teaching nursing assistant students about aphasia and communication.
AB  - Research indicates that communication between patients with communication
      disorders and their health care providers may be compromised, which leads to
      adverse outcomes and reduced participation in patients' own health care. Emerging
      studies demonstrate that effective communication education programs may decrease
      communication difficulties. This feasibility study of an education program that
      includes people with aphasia as educators aims to improve nursing assistant
      students' knowledge of aphasia and awareness of supported communication
      strategies while also examining the experiences of participants with aphasia.
      This preliminary study suggests that explicit aphasia and communication training
      delivered in this format has positive learning outcomes for nursing assistant
      students and potential psychosocial benefits to participants with aphasia. The
      format can be modified for a variety of health care audiences and lends itself to
      implementation by community aphasia groups and centers.

PMID- 21968561
TI  - Community: the key to building and extending engagement for individuals with
      aphasia.
AB  - The response by the aphasia community to the call of the Life Participation
      Approach to Aphasia Project Team to offer a framework for the management of
      aphasia was swift and expansive. Speech pathologists across the world accepted
      the paradigm shift from language goals within the clinic office to the short-term
      and long-term life objectives of their clients. The definition of service now
      included access to those communicative barriers that persons with aphasia face
      within their community. The recruitment, training, and shaping of that engagement
      must be individualized for successful (re)engagement. This article aims to
      present perspective on that process from a program that utilizes a unique center
      without walls concept.

PMID- 21968562
TI  - Starting an aphasia center?
AB  - Starting an aphasia center can be an enormous challenge. This article provides
      initial issues to review and consider when deciding whether starting a new
      organization is right for you. Determining the need for the program in your
      community, the best size and possible affiliation for the organization, and
      available resources, as well as developing a business plan, marketing the
      program, and building awareness in the community, are some of the factors that
      are discussed. Specific examples related to starting the Aphasia Center of
      California are provided.

PMID- 21968564
TI  - What makes a Journal Great?

PMID- 21968565
TI  - Iron-catalyzed ene-type propargylation of diarylethylenes with propargyl
      alcohols.
AB  - The diarylalkenyl propargylic complex framework has been found in many natural
      products and medicinal regents. Herein, we have disclosed an unprecedented
      FeCl(3) catalyzed ene-type reaction of propargylic alcohols with 1,1-diaryl
      alkenes which enabled us to furnish a diarylalkenyl propargylic complex framework
      in moderate to high chemical yields (up to 98%).

PMID- 21968566
TI  - Dissociating frontotemporal contributions to semantic ambiguity resolution in
      spoken sentences.
AB  - Comprehension of sentences containing semantically ambiguous words requires
      listeners to select appropriate interpretations, maintain linguistic material in
      working memory, and to reinterpret sentences that have been misinterpreted. All
      these functions appear to involve frontal cortical regions. Here, we attempt to
      differentiate these functions by varying the relative timing of an ambiguous word
      and disambiguating information in spoken sentences. We compare the location,
      magnitude, and timing of evoked activity using a fast-acquisition semisparse
      functional magnetic resonance imaging sequence. The left inferior frontal gyrus
      (LIFG) shows a strong response to sentences that are initially ambiguous
      (disambiguated by information that occurs either soon after the ambiguity or that
      is delayed until the end of the sentence). Response profiles indicate that
      activity, in both anterior and posterior LIFG regions, is triggered both by the
      ambiguous word and by the subsequent disambiguating information. The LIFG also
      responds to ambiguities that are preceded by disambiguating context. These
      results suggest that the LIFG subserves multiple cognitive processes including
      selecting an appropriate meaning and reinterpreting sentences that have been
      misparsed. In contrast, the left inferior temporal gyrus responds to the
      disambiguating information but not to the ambiguous word itself and may be
      involved in reprocessing sentences that were initially misinterpreted.

PMID- 21968567
TI  - Network centrality in the human functional connectome.
AB  - The network architecture of functional connectivity within the human brain
      connectome is poorly understood at the voxel level. Here, using resting state
      functional magnetic resonance imaging data from 1003 healthy adults, we
      investigate a broad array of network centrality measures to provide novel
      insights into connectivity within the whole-brain functional network (i.e., the
      functional connectome). We first assemble and visualize the voxel-wise (4 mm)
      functional connectome as a functional network. We then demonstrate that each
      centrality measure captures different aspects of connectivity, highlighting the
      importance of considering both global and local connectivity properties of the
      functional connectome. Beyond "detecting functional hubs," we treat centrality as
      measures of functional connectivity within the brain connectome and demonstrate
      their reliability and phenotypic correlates (i.e., age and sex). Specifically,
      our analyses reveal age-related decreases in degree centrality, but not
      eigenvector centrality, within precuneus and posterior cingulate regions. This
      implies that while local or (direct) connectivity decreases with age, connections
      with hub-like regions within the brain remain stable with age at a global level.
      In sum, these findings demonstrate the nonredundancy of various centrality
      measures and raise questions regarding their underlying physiological mechanisms
      that may be relevant to the study of neurodegenerative and psychiatric disorders.

PMID- 21968568
TI  - Hemispheric asymmetry of visual scene processing in the human brain: evidence
      from repetition priming and intrinsic activity.
AB  - Asymmetrical specialization of cognitive processes across the cerebral
      hemispheres is a hallmark of healthy brain development and an important
      evolutionary trait underlying higher cognition in humans. While previous
      research, including studies of priming, divided visual field presentation, and
      split-brain patients, demonstrates a general pattern of right/left asymmetry of
      form-specific versus form-abstract visual processing, little is known about brain
      organization underlying this dissociation. Here, using repetition priming of
      complex visual scenes and high-resolution functional magnetic resonance imaging
      (MRI), we demonstrate asymmetrical form specificity of visual processing between
      the right and left hemispheres within a region known to be critical for
      processing of visual spatial scenes (parahippocampal place area [PPA]). Next, we
      use resting-state functional connectivity MRI analyses to demonstrate that this
      functional asymmetry is associated with differential intrinsic activity
      correlations of the right versus left PPA with regions critically involved in
      perceptual versus conceptual processing, respectively. Our results demonstrate
      that the PPA comprises lateralized subregions across the cerebral hemispheres
      that are engaged in functionally dissociable yet complementary components of
      visual scene analysis. Furthermore, this functional asymmetry is associated with
      differential intrinsic functional connectivity of the PPA with distinct brain
      areas known to mediate dissociable cognitive processes.

PMID- 21968569
TI  - Colorectal cancer cell surface protein profiling using an antibody microarray and
      fluorescence multiplexing.
AB  - The current prognosis and classification of CRC relies on staging systems that
      integrate histopathologic and clinical findings. However, in the majority of CRC
      cases, cell dysfunction is the result of numerous mutations that modify protein
      expression and post-translational modification(1). A number of cell surface
      antigens, including cluster of differentiation (CD) antigens, have been
      identified as potential prognostic or metastatic biomarkers in CRC. These
      antigens make ideal biomarkers as their expression often changes with tumour
      progression or interactions with other cell types, such as tumour-infiltrating
      lymphocytes (TILs) and tumour-associated macrophages (TAMs). The use of
      immunohistochemistry (IHC) for cancer sub-classification and prognostication is
      well established for some tumour types(2,3). However, no single 'marker' has
      shown prognostic significance greater than clinico-pathological staging or gained
      wide acceptance for use in routine pathology reporting of all CRC cases.  A more
      recent approach to prognostic stratification of disease phenotypes relies on
      surface protein profiles using multiple 'markers'. While expression profiling of
      tumours using proteomic techniques such as iTRAQ is a powerful tool for the
      discovery of biomarkers4, it is not optimal for routine use in diagnostic
      laboratories and cannot distinguish different cell types in a mixed population.
      In addition, large amounts of tumour tissue are required for the profiling of
      purified plasma membrane glycoproteins by these methods.  In this video we
      described a simple method for surface proteome profiling of viable cells from
      disaggregated CRC samples using a DotScan CRC antibody microarray. The 122
      antibody microarray consists of a standard 82-antibody region recognizing a range
      of lineage-specific leukocyte markers, adhesion molecules, receptors and markers
      of inflammation and immune response(5), together with a satellite region for
      detection of 40 potentially prognostic markers for CRC. Cells are captured only
      on antibodies for which they express the corresponding antigen. The cell density
      per dot, determined by optical scanning, reflects the proportion of cells
      expressing that antigen, the level of expression of the antigen and affinity of
      the antibody(6).  For CRC tissue or normal intestinal mucosa, optical scans
      reflect the immunophenotype of mixed populations of cells. Fluorescence
      multiplexing can then be used to profile selected sub-populations of cells of
      interest captured on the array. For example, Alexa 647-anti-epithelial cell
      adhesion molecule (EpCAM; CD326), is a pan-epithelial differentiation antigen
      that was used to detect CRC cells and also epithelial cells of normal intestinal
      mucosa, while Phycoerythrin-anti-CD3, was used to detect infiltrating T-cells(7).
      The DotScan CRC microarray should be the prototype for a diagnostic alternative
      to the anatomically-based CRC staging system.

PMID- 21968570
TI  - Cross-sectional association between blood pressure, in vivo insulin sensitivity
      and adiponectin in overweight adolescents.
AB  - AIMS: To examine the cross-sectional relationship between blood pressure (BP) and
      (1) in vivo insulin sensitivity (IS) and (2) circulating adiponectin levels in
      overweight adolescents, and to determine if these relationships are driven by
      adiposity. METHODS: Sixty-five white pubertal overweight adolescents underwent a
      hyperinsulinemic-euglycemic clamp to measure IS. Body composition and abdominal
      adiposity were determined by dual energy X-ray absorptiometry and computed
      tomography scan. BP was measured by an automated sphygmomanometer every 10 min
      over 1 h, between 06:00 and 07:00 a.m. RESULTS: In vivo IS was not associated
      with BP after adjustment for adiposity measurements (body mass index, percentage
      body fat or abdominal adiposity). However, adiponectin was inversely related to
      systolic BP independent of adiposity. CONCLUSION: Our findings demonstrate that
      in overweight adolescents the relationship between in vivo IS and systolic BP is
      mediated through adiposity. However, the association between adiponectin and BP
      is independent of adiposity suggestive of a potential modulatory role of
      adiponectin in BP regulation.

PMID- 21968571
TI  - Smoking cessation and outcome in stable outpatients with coronary,
      cerebrovascular, or peripheral artery disease.
AB  - BACKGROUND: The influence of smoking cessation on outcome in patients with
      peripheral arterial disease (PAD) has not been thoroughly studied. METHODS: FRENA
      is an ongoing registry of stable outpatients with symptomatic coronary artery
      disease (CAD), cerebrovascular disease (CVD), or PAD. We compared the mortality
      rate of those who quit vs. those who continued smoking. RESULTS: As of December
      2010, 3523 patients were recruited, of whom 1182 (34%) were current smokers. Of
      these, 475 patients (40%) had CAD, 240 (20%) had CVD, and 467 (40%) had PAD. In
      all, 512 patients (43%) quit smoking. Over a mean follow-up of 14 months, 32
      patients (2.7%) died and 95 (8.0%) had subsequent ischaemic events (myocardial
      infarction 32, ischaemic stroke 20, critical limb ischaemia/disabling
      claudication 53). In patients with CAD, the mortality rate was significantly
      lower in recent quitters (0.77 vs. 3.73 deaths per 100 patient-years; p = 0.013)
      than in persistent smokers. No quitter with CVD died (0.0 vs. 2.18 deaths; p =
      0.092); but in patients with PAD there was a trend towards a higher mortality in
      quitters than in those who continued smoking (4.29 vs. 2.27 deaths; p = 0.357).
      On multivariate analysis, the relative risk for death in quitters was 0.20 (95%
      CI 0.05-0.75) in patients with CAD, 0.0 in those with CVD, and 1.83 (95% CI 0.65
      5.15) in those with PAD. CONCLUSIONS: Smoking cessation was associated with a
      significant decrease in mortality in patients with CAD, a non-significant
      decrease in those with CVD, and a non-significant increase in those with PAD.

PMID- 21968572
TI  - Sleep loss due to worry and future risk of cardiovascular disease and all-cause
      mortality: the Scottish Health Survey.
AB  - BACKGROUND: The association between specific sleeping disorders and risk of
      cardiovascular disease (CVD) is unclear. We assessed the association between
      sleep loss due to worry and future risk of CVD and death in a representative
      sample of community dwelling adults. METHODS: A cohort of 11,905 adults (aged
      53.4 +/- 12.2 years, 42.2% male) without known history of CVD were drawn from the
      Scottish Health Surveys. Self-reported sleep disturbance was measured using a
      single item from the General Health Questionnaire. Incident CVD events
      (comprising CVD death, nonfatal myocardial infarction, coronary surgical
      procedures, stroke, and heart failure) over 8-year follow up were ascertained by
      a linkage to national registers; a total of 1448 CVD events and 1249 all-cause
      deaths were recorded. RESULTS: 15.6% of the sample reported 'rather more' or
      'much more than usual' sleep loss due to worry over the prior 4 weeks. Sleep loss
      due to worry (much more than usual) was associated with elevated risk of CVD [age
      and sex-adjusted hazard ratio (HR) 1.74, 95% confidence interval (CI) 1.35-2.25]
      and all-cause mortality (age- and sex-adjusted HR 2.02, 95% CI 1.57-2.61).
      Adjustment for a range of psychosocial, behavioural, and clinical risk factors
      partly attenuated the association, and in particular health behaviours (smoking,
      alcohol, physical inactivity) accounted for approximately 40% of the sleep-CVD
      relation. CONCLUSION: Sleep loss due to worry was associated with a greater risk
      of CVD and all-cause mortality, but the association can be largely explained by
      intermediate risk factors such as health behaviours.

PMID- 21968573
TI  - Anterior cervical discectomy and fusion versus anterior cervical corpectomy and
      fusion for multilevel cervical spondylosis: a systematic review.
AB  - INTRODUCTION: There is considerable controversy as to which technique is best
      option for reconstruction after multilevel anterior decompression for cervical
      spondylosis. The aim of this study was to compare the clinical and radiographic
      results and complications of anterior cervical discectomy fusion (ACDF) and
      anterior cervical corpectomy fusion (ACCF) in the treatment of multi-level
      cervical spondylosis. METHOD: We reviewed and analyzed papers published from Jan
      1969 to Dec 2010 regarding the comparison of ACDF and ACCF for multilevel
      cervical spondylosis. Statistical comparisons were made when appropriate.
      RESULTS: Twelve studies were included in this systematic review. Blood loss was
      greater for ACCF compared with ACDF. Similarly, the rate of graft dislodgement in
      ACCF was higher than that in ACDF. Nonunion rates were 18.4% for 2-level ACDF and
      37.3% for 3-level ACDF, whereas nonfusion rates were 5.1% for single-level ACCF
      and 15.2% for 2-level ACCF. In addition, nonunion rates for three disc levels
      fused were much higher than that for two disc levels fused, regardless of
      discectomy or corpectomy. Clinical outcome was compared between ACDF and ACCF in
      nine studies. Of these, similar outcome was found between ACDF and ACCF in six
      studies, whereas three studies reported better outcome in ACCF compared with
      ACDF. CONCLUSION: Nonunion rates of ACDF are higher than those of ACCF for
      multilevel cervical spondylosis. Sometimes, clinical outcome of ACCF was better
      than ACDF for multilevel cervical spondylosis.

PMID- 21968574
TI  - A generative tool for building health applications driven by ISO 13606
      archetypes.
AB  - The use of Electronic Healthcare Records (EHR) standards in the development of
      healthcare applications is crucial for achieving the semantic interoperability of
      clinical information. Advanced EHR standards make use of the dual model
      architecture, which provides a solution for clinical interoperability based on
      the separation of the information and knowledge. However, the impact of such
      standards is biased by the limited availability of tools that facilitate their
      usage and practical implementation. In this paper, we present an approach for the
      automatic generation of clinical applications for the ISO 13606 EHR standard,
      which is based on the dual model architecture. This generator has been
      generically designed, so it can be easily adapted to other dual model standards
      and can generate applications for multiple technological platforms. Such good
      properties are based on the combination of standards for the representation of
      generic user interfaces and model-driven engineering techniques.

PMID- 21968576
TI  - Usefulness of Doppler derived end diastolic flow gradient across the patent
      ductus arteriosus in selecting coils for ductal occlusion.
AB  - Transcatheter closure of patent ductus arteriosus (PDA) with coils is accepted as
      an alternative to surgical ligation. We evaluated whether flow gradient across
      PDA, obtained by Doppler echocardiography, can aid in selecting coils for
      percutaneous ductal occlusion. 79 consecutive patients with PDA, who underwent
      successful percutaneous coil occlusion were retrospectively reviewed. Patients
      with other structural heart disease and pulmonary hypertension with right-to-left
      shunt were excluded. Echocardiogram and cardiac catheterization were done in all
      patients. Gianturco (Occluding Spring Emboli; Cook, Bloomington, IN) non
      detachable coils of 0.038 and 0.052-inch core sizes were used for ductal
      occlusion. Trough diastolic gradient was correlated with the size and the number
      of coils used. Mean age was 8.6 years (range 1.3 to 27 years); 24 males and 55
      females; PDA diameter ranged from 1.3 to 4.5 mm. Number of coils used varied from
      1 to 4. Echocardiography measured PDA size was 2.5 +/- 0.6 mm and significantly
      differed from angiographically measured size 2.9 +/- 0.6 mm (P = 0.05). End
      diastolic gradient below 38 mmHg predicted use of multiple coils or coils with
      larger surface area. End diastolic gradient correlated inversely with total
      surface area of the coils, which indirectly predicted size and number of coils.
      Thus, the prediction of the size and the number of coils for PDA occlusion can be
      assisted by the trough diastolic gradients of PDA.

PMID- 21968575
TI  - Exploration of the valproic acid binding site on histone deacetylase 8 using
      docking and molecular dynamic simulations.
AB  - Epigenetic therapy is an important focus of research for drug development in the
      treatment of cancer. Valproic acid (VPA) is an HDAC inhibitor that has been
      evaluated in clinical studies. Despite its success in treating cancer, the
      mechanism of inhibition of VPA in HDAC is unknown. To this end, we have used
      docking and molecular dynamic simulations to investigate VPA binding to HDAC,
      employing both native and rebuilt 3-D structures. The results showed that VPA,
      via its carboxyl group, coordinates the Zn atom and other local residues (H141
      142 and Y360) located at the catalytic site (CS) of HDAC. This causes
      electrostatic and hydrogen bonding interactions while having little interaction
      with the hydrophobic side chains, resulting in a low affinity. However, after
      several docking studies on different native HDAC 3-D structures and after using
      several snapshots from MD simulations, it became apparent that VPA bound with
      highest affinity at a site located at the acetyl-releasing channel, termed the
      hydrophobic active site channel (HASC). The affinity of VPA for HASC was due to
      its highly hydrophobic properties that allow VPA to take part in van der Waals
      interactions with Y18, I19, Y20, V25, R37, A38, V41, H42, I135 and W137, while
      VPA's carboxylate group has several hydrogen bonding interactions with the
      backbones of S138, I19, N136 and W137. MD simulations showed that the HASC door
      continuously opened and closed, which affected the affinity of VPA to the HASC,
      but the affinity toward the HASC was consistently higher than that obtained for
      the CS, suggesting that the HASC could be involved in the mechanism of
      inhibition.

PMID- 21968577
TI  - Right ventricle myocardial perfusion scintigraphy: feasibility and expected
      values in children.
AB  - Stress myocardial perfusion scintigraphy imaging (SMPSI) has important
      applications for evaluating coronary disease and ventricular function. Studies
      consistently focus on the left ventricle (LV), with no normal right ventricle
      (RV) data available. This study sought to evaluate the feasibility of RV
      perfusion with technetium (Tc-99m) sestamibi using a low radiotracer dose for
      children free of coronary artery (CA) anomalies and to determine its normal
      pattern. Patients with a history of Kawasaki disease who showed no coronary
      complications on selective angiography or no LV perfusion defects on SMPSI were
      studied at rest and during an exercise challenge. The RV uptake counts were
      compared with those for different segments of the LV, and multiple ratios of the
      uptakes between RV and LV segments were calculated. The study subjects were 23
      children (age, 11.1 +/- 3.3 years) imaged with 0.12 +/- 0.03 mCi/kg at rest and
      0.31 +/- 0.06 mCi/kg during stress. The RV to LV uptake proportion was
      approximately 6%. Exercise-related uptake increased threefold in both the RV and
      the LV. The findings showed RV myocardial scintigraphy to be feasible with
      reproducible ratios. Potential clinical applications include acquired and
      congenital CA anomalies such as Kawasaki disease, right CA ostium stenosis after
      a switch operation, and anomalous origin of the right CA.

PMID- 21968579
TI  - Atypical partial anomalous pulmonary venous drainage of the left upper pulmonary
      vein through a compressed vertical vein between the aorta and the pulmonary
      artery.

PMID- 21968578
TI  - Heterogeneity of ventricular repolarization in newborns with severe aortic
      coarctation.
AB  - Sudden death is a possible occurrence for newborns younger than 1 year with
      severe aortic coarctation (CoA) before surgical correction. Basic research and
      animal experiments have shown electrophysiologic changes during mechanical
      ventricular pressure overload. The current study aimed to evaluate the effect of
      severe CoA on the heterogeneity of ventricular repolarization by examining
      corrected QT and JT interval dispersion (respectively, QTc-D and JTc-D) and
      electrocardiographic parameters of spatial heterogeneity of ventricular
      repolarization in newborns with no associated congenital cardiac malformations.
      The study enrolled 30 isolated severe CoA neonates (age, 45 +/- 15 days; 17
      males) with normal size and wall thickness of the left ventricle before surgical
      correction and 30 age- and sex-matched healthy newborns used as control subjects.
      Heart rate, QRS duration, maximum and minimum QT and JT intervals, and QTc-D and
      JTc-D measurements were performed. The healthy control group did not
      significantly differ from the CoA group in terms of heart rate, weight, height,
      and echocardiographic parameters. Compared with the healthy control group, the
      CoA group presented significantly increased values of QTc-D (109.7 +/- 43.4 vs.
      23 +/- 15 ms; P = 0.03) and JTc-D (99.1 +/- 43.3 vs. 65.8 +/- 24.1 ms; P = 0.04).
      A statistically significant correlation was found between the Doppler peak
      pressure gradient across the coarctation site and the values of QTc-D (r = 0.48;
      P = 0.03) and JTc-D (r = 0.42; P = 0.04). Our study showed significantly
      increased QTc-D and JTc-D in isolated CoA newborns with normal left ventricular
      geometry.

PMID- 21968580
TI  - The pros and cons of diagnostic-therapeutic protocols for clinical practice and
      teaching in neurosurgery.

PMID- 21968581
TI  - Biochemical markers analyzed using microdialysis and traumatic brain injury
      outcomes.
AB  - AIM: Traumatic brain injury is a leading cause of disability and mortality among
      young people. Multiparametric cerebral bedside monitoring is a safe and promising
      technique for preventing secondary brain damage. The objective of this study was
      to investigate the usefulness of cerebral microdialysis in predicting the
      outcomes of patients with traumatic brain injury. METHODS: Thirty-eight patients
      (33 males) were included in the study. The GCS on admission was <=8. The outcome
      was assessed using the GOS over six months of follow-up. RESULTS: Among the
      patients included, 18 had a favorable outcome (GOS=4.5) and the remaining 20 had
      an unfavorable outcome. L/P ratio and glycerol concentration were statistically
      significantly higher in the patients with unfavorable prognosis. CONCLUSION:
      Biochemical parameters analysed using microdialysis could serve as predictor
      indexes of clinical outcome several months after the injury.

PMID- 21968582
TI  - Use of multimodal electrophysiological monitoring to predict outcome after
      subarachnoid hemorrhage? A prospective series.
AB  - AIM: Electrophysiological monitoring (EM) is still controversial in the
      prediction of outcome after subarachnoid hemorrhage (SAH). The absence of evoked
      potentials (EP) is a good predictor for unfavorable, whereas the prediction of
      favorable outcome may be less useful. Aim of this study was to evaluate, if
      multimodal EM provides significant information about the patients' outcome or if
      this method might be dispensable. METHODS: Multimodal EP data were recorded
      sequentially in 51 SAH-patients. The following data were recorded: World
      Federation of Neurological Surgeons (WFNS-) grade, Fisher grading score,
      endovascular versus neurosurgical treatment, aneurysm location and clinical
      outcome according to the Glasgow Outcome Scale (GOS). Multimodal
      electrophysiological monitoring included median nerve somatosensory evoked
      potential (M-SSEP), tibial nerve somatosensory evoked potential (T-SSEP), flash
      visual evoked potential (f-VEP), brainstem auditory evoked potential (BAEP) and
      central conduction time (CCT) of M-SSEP. EP data were recorded sequentially; the
      first and last studies were evaluated. RESULTS: No correlation was found between
      initial and last M-SSEP, T-SSEP, BAEP and initial f-VEP and the patients'
      outcome. An 'unfavorable' outcome was in conjunction with an initial delayed CCT
      (>6 ms, P=0.03) and the final f-VEP correlated well with the patients' outcome
      (P=0.03). CONCLUSION: In conclusion, neither T-SSEP, f-VEP, BAEP nor CCT can be
      used as valid predictor for outcome after SAH. The patient's initial clinical
      grading still provides the only satisfying predictor, independent of the
      patient's clinical course.

PMID- 21968583
TI  - An expandable prosthesis with dual cage-and-plate function in a single device for
      vertebral body replacement: the clinical experience on 14 consecutive cases with
      vertebral tumors.
AB  - AIM: The aim of this paper was to test the hypothesis that an expandable
      prosthesis with dual cage-and-plate function can provide immediate and durable
      spine stabilization after corpectomy. METHODS: We designed an expandable
      vertebral body prosthesis with dual cage-and-plate function in a single device
      (JR-prosthesis). Anatomical studies were performed to design a titanium-made
      prosthesis. Cadaver assays were done with a stainless steal device to test
      fixation and adequacy to the human spine anatomy. Then, 14 patients with
      vertebral tumors (8 metastatic) underwent corpectomy and vertebral body
      replacement with the JR-prosthesis. RESULTS: All patients had neurological
      deficit, severe pain and spine instability (mean follow-up: 25.4 months). Mean
      pain score before surgery in a visual analog scale improved from 7.6 to 3.0
      points after operation (P=0.002). All patients achieved at least one grade of
      improvement in the Frankel score (P=0.003), excepting the 3 patients with Frankel
      grade A presurgery. Two patients with renal cell carcinoma died during the
      following 4 days after surgery (renal failure and massive bleeding), the rest
      attained a painless and stable spine immediately and maintained for long periods.
      No significant infections or implant failures were registered. A non-fatal case
      of inferior vena cava surgical injury was observed (repaired during surgery
      without further complications). CONCLUSION: The JR-prosthesis stabilizes the
      spine immediately after surgery and for the rest of the patients' life. To our
      knowledge, this is the first report on the clinical experience of any expandable
      vertebral body prosthesis with dual cage-and-plate function in a single device.
      These observations await confirmation in different scenarios.

PMID- 21968584
TI  - Stereotactic radiosurgery for spinal metastases: update on treatment strategies.
AB  - Metastatic tumors are the most common tumors that affect the spinal column and
      are the source of significant pain and disability in cancer patients. The
      management of symptomatic spinal metastases presents unique challenges to
      surgeons as a number of considerations specific to the underlying tumor
      histology, extent of disease, the functional status of the patient and response
      to systemic therapy often affect the role, timing and effectiveness of any
      surgical intervention. As surgical techniques have evolved, the focus of therapy
      has shifted towards minimizing the morbidity associated with treatments for
      patients in whom limited nutrition and functional reserve impact their overall
      survival. As such, stereotactic spinal radiosurgery (SRS) has emerged as a
      powerful adjunct to surgery as well as a stand-alone treatment option for
      patients with metastatic disease. Recent technological innovations such as
      intensity-modulated radiation therapy, image-guidance, and non-invasive spine
      immobilization have made significant improvements to the delivery of highly
      conformal radiation to spinal tumors. In this article, current treatment
      strategies utilizing SRS in the multidisciplinary management of spinal metastases
      are discussed.

PMID- 21968586
TI  - Interventional neurovascular disease: avoidance and management of complications
      and review of the current literature.
AB  - There has been a substantial increase in the number of neuroendovascular
      procedures performed over the last 15 years. Although rare, complications of
      cerebral angiography and neuroendovascular procedures have the potential to be
      devastating. Fortunately, dedication to careful patient selection, meticulous
      attention to technical detail, and standardization of endovascular treatment
      protocols results in an acceptably low complication rate. Factors that may
      predispose one to complications with cerebral angiography include age, smoking,
      functional stats, medical comorbidities, and duration of the procedure. The most
      common complication of angiography is vascular access site complication, with a
      rate of up to 5%. The overall neurologic complication rate for diagnostic
      angiography is 1.3-2.6%, with a permanent neurologic deficit rate of 0.14-0.50%.
      Neuroendovascular interventions are more invasive, take longer to perform, and
      have higher rates of complication. Procedure specific complications include
      aneurysm rupture, arterial dissection, stroke, hemorrhage, thromboembolism, and
      microembolism, and rates of neurologic deficit are higher than those for
      diagnostic angiography. With knowledge of the common complications, strategies to
      minimize them, and a meticulous attention to the technical detail of the
      procedure, complications of neuroendovascular interventions can be minimized.

PMID- 21968585
TI  - The current surgical management of intracranial aneurysms.
AB  - For more than two decades, surgical clipping of ruptured intracranial aneurysms
      was considered the stan-dard of care. However, as technology improved, a new
      treatment option was developed, endovascular emoblization. The treatment of
      cerebral aneurysms, is now in an era where deciding when to clip versus coil can
      be difficult. Today's cerebrovascular specialist must consider a multitude of
      factors when developing the best treatment strategy for an individual patient.
      Optimal management requires a thorough understanding of the natural history of
      aneurysms as well as risks and benefits related to the different treatment
      modalities. The purpose of this article is not to proclaim one treatment better
      than the other, but rather to provide the reader with an up-to-date,
      comprehensive insight into the management of cerebral aneurysms. We will review
      data regarding the natural history of aneurysms along with the effectiveness of
      both surgical clipping and endovascular embolization. We will further discuss our
      current management strategy for some of the most common aneurysms encountered.
      The successful treatment of intracranial aneurysms requires a multidisciplinary
      approach, where surgery and endovascular therapies are viewed as complimentary
      instead of competing.

PMID- 21968587
TI  - Cranial neuroendoscopy: novel applications and next frontiers.
AB  - Neuroendoscopy is an ever-evolving frontier in neurosurgery and its use has
      spanned decades with safe and efficacious treatment in a variety of cranial
      procedures. There are areas of technology that are broadening the cranial use of
      the endoscope. Here we discuss the foundations of cranial neuroendoscopy in the
      areas of cerebrospinal fluid diversion and tumor biopsy and discuss the recent
      advancements in the areas of craniosynostosis, endonasal surgery, ventriculo
      cisternal approaches, brain parenchymal surgery and skull base surgery. We
      highlight the ongoing evolution of neuroendoscopic technology and consider the
      potential future applications that will help to revolutionize the current
      standards in endoscopy and its use inn neurosurgical practice.

PMID- 21968588
TI  - The surgical technique of minimally invasive transforaminal lumbar interbody
      fusion.
AB  - We aim to describe the minimally invasive transforaminal lumbar interbody fusion
      (MI-TLIF) technique. The MI-TLIF procedure was developed to achieve the same goal
      of neural decompression and interbody arthrodesis as the traditional, open TLIF
      techniques. MI-TLIF has been utilized in the treatment of an array of lumbar
      pathologies, while offering the advantages of reducing soft tissue trauma,
      decreasing postoperative pain, and reducing the rate of complication when
      compared to the open techniques. The surgical technique of MI-TLIF is described
      in a step-by-step fassion. A technical review of this novel minimally invasive
      procedure was performed. Additionally, data collected through our experience with
      this procedure is reported. Data was collected retrospectively from patients
      between January 2008 and December 2009 who underwent MI-TLIF. The mean
      preoperative VAS score was 6.12+/-2.02 compared to 2.11+/-2.69 postoperatively.
      The mean ODI score dropped from 38.29+/-13.19 preoperatively to 16.00 +/-16.598
      postoperatively. Eighty-four patients who underwent MI-TLIF between October 2007
      and December 2010 were divided based on age (over or under 65 years) and
      intraoperative estimated blood loss (EBL) was compared. The mean EBL for the
      young age group was 93.37+/-102.16 mL compared to 100 +/-61.24 mL for the older
      group. Operation times for the MI-TLIF procedure has decreased from 3-4 hours to
      approximately 2 hours throughout our experience with this technique. The MI-TLIF
      technique is a safe and effective procedure offering the advantages of less
      tissue damage, less blood loss, and reduced postoperative hospitalization over
      the open techniques.

PMID- 21968589
TI  - Practical and technical aspects of trans-sphenoidal surgery.
AB  - Trans-sphenoidal surgery was first described more than a century ago. Today, this
      approach occupies a crucial place in the armamentarium of the neurosurgeon for
      the management of sellar, suprasellar, and parasellar pathological conditions.
      Over the years, the procedure has witnessed multiple modifications, benefitting
      from technological advances and from innovative ideas of pioneering neurosurgeons
      and otolaryngologists. The introduction of the microscope and then the endoscope
      allowed progressive improvement of visualization, illumination, and magnification
      in this restricted surgical corridor. With enhanced knowledge and understanding
      of the surgical anatomy of the skull base, the application of extended
      transsphenoidal approaches became possible, thus widening significantly the
      anatomical area that can be reached through this approach. In addition, the
      continuous improvement in imaging, image guidance, and microinstruments allowed
      better planning and precision during surgery. In sum, thanks to recent
      technological advance, trans-sphenoidal surgery can now be applied to a large
      area of the skull base and for a wide range of pathological conditions. With
      growing experience, the procedure is performed with enhanced safety and greater
      efficacy. In this paper, we review the historical evolution of trans-sphenoidal
      surgery and describe the modern applications and modifications of the procedure.

PMID- 21968590
TI  - Prevention of scar tissue formation in spinal surgery: state of the art and
      review of the literature.
AB  - Recurrent radicular pain after lumbar micro-discectomy may lead to reduced
      quality of life of the patient. Lumbar epidural fibrosis is believed to be one of
      the mechanisms involved in the genesis of the pain. The use of absorbable gel
      temporarily separating disc remnants, muscle or bone structures from the nerve
      roots could reduce the amount of scar tissue surrounding the nerve, reduce
      tethering and therefore pain, improve outcomes and facilitate revision surgery.
      The author reviews the literature on prevention techniques for lumbar epidural
      fibrosis. The most recent studies on new compounds are encouraging in terms of
      safety and clinical efficacy.

PMID- 21968591
TI  - Management of calcified thoracic disc herniation using ultrasonic bone curette
      SONO-PET(r): technical description.
AB  - This paper describes the surgical management of a post-traumatic calcified
      thoracic disc herniation treated using ultrasonic bone curette SONO-PET(r). The
      case described concerns a young man with a symptomatic calcified thoracic disc
      herniation, who underwent posterolateral approach and
      transversoarthropediculectomy. Patient underwent posterolateral approach with
      excellent postoperative results. Neurophysiological monitoring somato-sensory
      evoked potential (SSEP) and muscle motor evoked potentials (MMEP), inclination of
      30 degrees  toward the unaffected side of the operating table, the use of
      Ultrasonic Bone-Curette SONO-PET(r) and proper reconstruction of the three floors
      of the back muscles allows the removal of the disc herniation safer and risk's
      free, and less invasive for the patient.

PMID- 21968592
TI  - Syncope revealing a ruptured sacral dermoid cyst in an 84-year-old man: case
      report.

PMID- 21968594
TI  - Angiogenesis is a link between atherosclerosis and tumorigenesis: role of LOX-1.
AB  - Angiogenesis is defined as the formation of new blood vessels sprouting from pre
      existing vessels. It plays an important role not only in physiological situations
      such as embryonic vascular development and wound healing, but also in
      pathological conditions including atherogenesis and evolution and spread of
      certain tumors. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1),
      a receptor for oxidized low density lipoprotein (ox-LDL), is mainly expressed in
      endothelial cells. It has diverse physiological functions and it could be a link
      between atherogenesis and tumorigenesis. The risk factors for atherosclerosis
      like hypertension, diabetes mellitus and hyperlipidemia are associated with LOX
      1. Dyslipidemia and obesity are also being recognized as risk factor for certain
      tumors. LOX-1 is also found to be important for maintaining the transformed state
      in developmentally diverse cancer cell lines and for tumor growth. There is
      emerging evidence that LOX-1 plays an important role in the angiogenesis process.
      In this review, we outline the roles of angiogenesis in atherogenesis and
      tumorigenesis, and describe the role of LOX-1 as a potential molecular target for
      blocking angiogenesis.

PMID- 21968595
TI  - Arthroscopic debridement for soft tissue ankle impingement.
AB  - AIM: To assess the response to treatment in patients with soft tissue impingement
      of the ankle managed with arthroscopic debridement. METHODS: Forty-one ankle
      arthroscopies were performed for soft tissue impingement between April 2007 and
      April 2009. There were 26 men and 15 women and the mean age was 30.1 years.
      Arthroscopy was performed on an average of 21 months after injury. The Visual
      Analogue-Scale Foot and Ankle (VASFA) score and Meislin's criteria were used to
      assess the response to treatment. RESULTS: The mean pre-operative VASFA score was
      44.5. This increased to 78.3 postoperatively (p < 0.0001). According to Meislin's
      criteria, there were 34 good or excellent results, five fair and two poor
      results. Pre-operative magnetic resonance imaging was useful in detecting tears
      of the anterior talofibular ligament and excluding osteochondral defects;
      however, synovitis and soft tissue impingement was under-reported. CONCLUSIONS:
      Arthroscopy is an effective method for the diagnoses and treatment of soft tissue
      impingement of the ankle joint. This condition is under-reported on MRI.

PMID- 21968596
TI  - [3T-AI: a new treatment algorithm for anal incontinence with a higher evidence
      level].
AB  - BACKGROUND: The evidence for conservative treatment of anal incontinence is poor.
      In our first publication [Schwandner et al. Dis Colon Rectum 2010; 53: 1007-1016]
      we demonstrated that a novel therapeutic concept, termed triple target treatment
      (3T), combining amplitude-modulated medium frequency stimulation and
      electromyography biofeedback (EMG-BF) was superior to EMG-BF alone. Questions
      about the required treatment duration and the relevant subgroups of patients with
      sphincter damage and damaged anal sensibility were not addressed. METHODS: We
      enrolled 158 patients with anal incontinence in this randomized study. Here, we 
      report on the important subgroup analyses of patients with and without sphincter
      damage and damaged anal sensibility for the endpoints Cleveland Clinic Score
      (CCS) and success record. Using the results of this study we propose a novel
      treatment algorithm which is open for discussion. RESULTS: In patients with
      sphincter damage, the median difference on the CCS from baseline to 9 months was
      5 points higher for 3T than for EMG-BF (95 % confidence interval 0-8; p =
      0.0168). While 47 % of the patients with sphincter damage became continent with
      3T, only 18 % did with EMG-BF (p = 0.0036). Ten of 17 patients in the 3T group
      regained anal sensibility after 3 months stimulation. There was tendency towards
      improved continence in patients with neuropathy upon 3T treatment (p = 0.1219).
      CONCLUSIONS: 3T is superior to EMG-BF alone for patients with sphincter damage
      and neuropathic anal incontinence. It is a successful key element within our
      treatment algorithm, even in patients with sphincter damage and neuropathic anal
      incontinence.

PMID- 21968597
TI  - Oxidative stress levels in exhaled breath condensate associated with COPD and
      smoking.
AB  - BACKGROUND: COPD is characterized by chronic air-flow limitation. Smoking is the
      most important factor in the pathogenesis of COPD. Smoking is associated with
      increased oxidative stress in the lungs. In this study our aim was to evaluate
      the differences in the burden of oxidative stress  in patients with COPD,
      smokers, and non-smokers by measuring hydrogen peroxide (H(2)O(2)),
      malondialdehyde (MDA), and 8-isoprostane levels in the exhaled breath condensate
      (EBC) samples. METHODS: Eighty subjects were included in the study. Group I (no.
      = 25) had COPD, Group  II (no. = 26) was smokers, and Group III (no. = 29) was
      nonsmokers. The severity of the COPD and dyspnea was assessed according to the
      results of pulmonary function tests (PFTs) and Medical Research Council (MRC)
      scale. RESULTS: The mean age of the subjects was 58 +/- 8.9 years. While  8
      isoprostane and H(2)O(2) levels were significantly higher in subjects with COPD
      (44.8 +/- 40.2 pg/mL and 1.9 +/- 0.8 MUmol/L) and smokers (41.3 +/- 26 pg/mL and
      1.7 +/- 0.7 MUmol/L) than non-smokers (15.8 +/- 6.9 pg/mL and 0.8 +/- 0.4
      MUmol/L),  levels were similar between smokers and COPD subjects. MDA levels were
      similar between the 3 groups (P = .31). There was no correlation between 8
      isoprostane and H(2)O(2) levels and PFT parameters. There was a significant
      positive correlation between dyspnea grade  on the MRC scale and 8-isoprostane
      levels (r = 0.805, P < .001). CONCLUSIONS: Even if respiratory function tests are
      within normal limits, oxidant burden in lungs of smokers is equivalent to that in
      COPD patients. 8-isoprostane could be useful in assessing symptom severity and
      health  status of COPD patients.

PMID- 21968598
TI  - Dynamical and energetic properties of hydrogen and hydrogen-tetrahydrofuran
      clathrate hydrates.
AB  - Classical equilibrium molecular dynamics (MD) simulations have been performed to
      investigate the dynamical and energetic properties in hydrogen and mixed hydrogen
      tetrahydrofuran sII hydrates at 30 and 200 K and 0.05 kbar, and also at
      intermediate temperatures, using SPC/E and TIP4P-2005 water models. The potential
      model is found to have a large impact on overall density, with the TIP4P-2005
      systems being on average 1% more dense than their SPC/E counterparts, due to the
      greater guest-host interaction energy. For the lightly-filled mixed H(2)-THF
      system, in which there is single H(2) occupation of the small cage (1s1l), we
      find that the largest contribution to the interaction energy of both types of
      guest is the van der Waals component with the surrounding water molecules in the
      constituent cavities. For the more densely-filled mixed H(2)-THF system, in which
      there is double H(2) occupation in the small cage (2s1l), we find that there is
      no dominant component (i.e., van der Waals or Coulombic) in the H(2) interaction
      energy with the rest of the system, but for the THF molecules, the dominant
      contribution is again the van der Waals interaction with the surrounding cage
      water molecules; again, the Coulombic component increases in importance with
      increasing temperature. The lightly-filled pure H(2) hydrate (1s4l) system
      exhibits a similar pattern vis-a-vis the H(2) interaction energy as for the
      lightly-filled mixed H(2)-THF system, and for the more densely-filled pure H(2)
      system (2s4l), there is no dominant component of interaction energy, due to the
      multiple occupancy of the cavities. By consideration of Kubic harmonics, there is
      some evidence of preferential alignment of the THF molecules, particularly at 200
      K; this was found to arise at higher temperatures due to transient hydrogen
      bonding of the oxygen atom in THF molecules with the surrounding cage-water
      molecules.

PMID- 21968600
TI  - Endothelial and axon reflex vasodilatation to acetylcholine in rosacea-affected
      skin.
AB  - Rosacea is a chronic skin disorder, characterized by persistent painful facial
      flushing and often accompanied by papules and pustules. To investigate the
      mechanism of facial flushing in rosacea, acetylcholine was administered by
      iontophoresis to a 10-mm diameter site in the forehead of 31 patients with
      rosacea and in 29 controls of similar age and sex distribution. During the
      iontophoresis, current strengths doubled in eight steps from 2.5 to 320 MUA. For
      each step, skin blood flow was monitored during 60 s of iontophoresis and for 2
      min afterwards with laser Doppler flow probes at the site of iontophoresis and 5
      8 mm away in the region of axon reflex vasodilatation. Vascular responses to
      acetylcholine were similar in patients and controls, but stinging sensations were
      greater in patients than in controls at the most intense current strength. In
      addition, axon reflex vasodilatation was greater in patients with severe than
      mild rosacea. These findings suggest that activation of nociceptive nerve fibres
      contributes to skin sensitivity in patients with rosacea, and that axon reflexes
      augment flushing in patients with the most severe symptoms.

PMID- 21968601
TI  - MicroRNA-146a modulates TGF-beta1-induced phenotypic differentiation in human
      dermal fibroblasts by targeting SMAD4.
AB  - During wound healing and tissue repair the dermal fibroblast-to-myofibroblast
      transdifferentiation plays an important role, transforming growth factor-beta1
      (TGF-beta1) is considered to be the main stimuli factor of transdifferentiation.
      MicroRNAs (miRNAs) have recently emerged as key post-transcriptional regulators
      of gene expression. The involvement of miRNAs and their roles in TGF-beta1
      induced myofibroblast transdifferentiation remains to be determined in detail.
      The current study found that the expression of miR-146a was upregulated in human
      dermal fibroblasts cells in response to TGF-beta1 stimulation in dose-dependent
      manner by quantitative RT-PCR. Bioinformatic analyses predict that signaling
      effectors mothers against decapentaplegic protein 4 (SMAD4) is a miR-146a target
      gene. Luciferase assay demonstrated that miR-146a mimics suppressed SMAD4 3'-UTR
      reporter construct activity. Furthermore, miR-146a overexpression in dermal
      fibroblast did not decrease target mRNA levels, but significantly reduced target
      protein expression. In addition, dermal fibroblasts transfected with miR-146a
      mimics exhibited attenuated TGF-beta1 -induced alpha-smooth muscle actin (alpha
      SMA) expression compared with the control. This study demonstrated that miR-146a
      may function as a novel negative regulator to modulate myofibroblast
      transdifferentiation during TGF-beta1 induction by targeting SMAD4.

PMID- 21968602
TI  - Natural killer cells and T cells induce different types of skin reactions during
      recall responses to haptens.
AB  - The role of T cells in contact hypersensitivity (CHS) to haptens has been well
      described. However, recent reports demonstrated that CHS-like reactions to
      experimental haptens could be induced in mice deficient in T cells and B cells,
      as a result of adaptive-like features of NK cells. Here, we compared hapten
      specific inflammatory reactions induced by memory T cells or NK cells. Classical
      CHS protocols were applied to WT or T- and B-cell deficient mice. Adoptive
      transfers of hapten-specific T cells and NK cells were also performed. Liver NK
      cells from hapten-primed mice induced specific recall responses to haptens upon
      transfer in CD3epsilon-deficient mice, thus confirming the existence of "memory"
      NK cells in the liver. We investigated the nature of the inflammation generated
      in these transfer conditions and found that hapten-induced skin inflammation
      mediated by CD8(+)  T cells or "memory" NK cells are different. Indeed, ear
      swelling induced by memory NK cells was transient and not associated with
      cellular infiltrate and inflammation markers, characteristic for T-cell-mediated
      responses. Thus, NK cells and T cells mediate distinct forms of skin
      inflammation. NK cell-mediated pathogenesis does not rely on cellular infiltrate
      and could be involved in atypical forms of adverse drug reactions.

PMID- 21968603
TI  - Treatment preferences among depressed patients after acute coronary syndrome: the
      COPES observational cohort.

PMID- 21968604
TI  - Characteristics of endophthalmitis with Boston keratoprosthesis.

PMID- 21968606
TI  - Expeditious diastereoselective construction of a thiochroman skeleton via a
      cinchona alkaloid-derived catalyst.
AB  - An example of diastereoselective and enantioselective synthesis of thiochroman
      derivatives through a sulfa-Michael-Michael cascade sequence is disclosed. This
      is a significant complement of the quinine-thiourea catalyzed sulfa-Michael
      Michael cascade reaction. The densely functionalized target thiochromans were
      obtained in high diastereoselectivities, and with high to excellent
      enantioselectivities.

PMID- 21968605
TI  - Effectiveness of artificial tears in the management of evaporative dry eye.
AB  - PURPOSE: To compare the efficacies of sodium hyaluronate, hydroxypropyl
      methylcellulose (HPMC), and a new oil-in-water emulsion (Emustil unidose; SIFI)
      in the management of lipid-deficient dry eye. METHODS: Seventy-five subjects with
      dry eye were randomly divided into 3 groups. Each was allocated sodium
      hyaluronate, HPMC, or emulsion eyedrops to be used four times daily for 90 days.
      Parameters were measured at baseline, 30 days, and 90 days. A compliance visit
      was performed at days 7 and 60. RESULTS: Significant reduction (P < 0.05) in
      evaporation and improvement in symptoms in all groups were found. No
      statistically significant increase in tear turnover rate (TTR) was found with any
      solution. A significant difference in tear stability and noninvasive tear break
      up time (NITBUT) was found in the emulsion and sodium hyaluronate groups but not
      in the HPMC group (P > 0.05). There was a significant decrease in osmolarity and
      corneal staining in the emulsion group (P < 0.001) but not in the sodium
      hyaluronate or HPMC group (P > 0.05). CONCLUSIONS: A significant reduction in
      evaporation and improvement in symptoms in all therapy groups were found from
      baseline to 90 days. However, no significant effect was seen on TTR for any
      group. The emulsion drops were shown to perform best, improving tear stability,
      and decreasing osmolarity and corneal staining. These results are consistent with
      improvements in the lipid layer of the tear film as a result of prolonged use of
      emulsion drops.

PMID- 21968607
TI  - Displacement of three dental implants into the maxillary sinus in two patients.
      Report of two cases.
AB  - INTRODUCTION: Reconstruction of the posterior edentulous maxilla with dental
      implants has become a popular practice worldwide. However, the poor bone quality
      and quantity in this area is sometimes related with complications. Dental implant
      displacement into the maxillary sinus is a rare complication. CASE REPORT: In the
      present paper, we present two patients with three implants displaced into the
      maxillary sinus. The implants were removed soon after their displacement, using
      the classic intraoral approach, through the anterior wall of the maxillary sinus.
      The operation was performed under local anesthesia for both of the patients. The
      postoperative course was uneventful for both of the patients without any wound
      dehiscence. Recovery remained uneventful, without any signs of postoperative
      sinusitis. DISCUSSION: Implant displacement into the maxillary sinus is of rare
      occurrence and usually related to inadequate bone quality and quantity. Dental
      implants into the maxillary sinus usually act as foreign bodies and should be
      removed, to avoid the development of sinus complications. Removal of dental
      implants from the maxillary sinus can be performed either with functional
      endoscopic sinus surgery, or with intraoral operation through the anterior
      maxillary wall especially in fresh cases and in the presence of oroantral
      communication.

PMID- 21968609
TI  - Formulation of diblock polymeric nanoparticles through nanoprecipitation
      technique.
AB  - Nanotechnology is a relatively new branch of science that involves harnessing the
      unique properties of particles that are nanometers in scale (nanoparticles).
      Nanoparticles can be engineered in a precise fashion where their size,
      composition and surface chemistry can be carefully controlled. This enables
      unprecedented freedom to modify some of the fundamental properties of their
      cargo, such as solubility, diffusivity, biodistribution, release characteristics
      and immunogenicity. Since their inception, nanoparticles have been utilized in
      many areas of science and medicine, including drug delivery, imaging, and cell
      biology(1-4). However, it has not been fully utilized outside of "nanotechnology
      laboratories" due to perceived technical barrier. In this article, we describe a
      simple method to synthesize a polymer based nanoparticle platform that has a wide
      range of potential applications.  The first step is to synthesize a diblock co
      polymer that has both a hydrophobic domain and hydrophilic domain. Using PLGA and
      PEG as model polymers, we described a conjugation reaction using EDC/NHS
      chemistry(5) (Fig 1).  We also discuss the polymer purification process. The
      synthesized diblock co-polymer can self-assemble into nanoparticles in the
      nanoprecipitation process through hydrophobic-hydrophilic interactions. The
      described polymer nanoparticle is very versatile. The hydrophobic core of the
      nanoparticle can be utilized to carry poorly soluble drugs for drug delivery
      experiments6. Furthermore, the nanoparticles can overcome the problem of toxic
      solvents for poorly soluble molecular biology reagents, such as wortmannin, which
      requires a solvent like DMSO. However, DMSO can be toxic to cells and interfere
      with the experiment. These poorly soluble drugs and reagents can be effectively
      delivered using polymer nanoparticles with minimal toxicity. Polymer
      nanoparticles can also be loaded with fluorescent dye and utilized for
      intracellular trafficking studies. Lastly, these polymer nanoparticles can be
      conjugated to targeting ligands through surface PEG. Such targeted nanoparticles
      can be utilized to label specific epitopes on or in cells(7-10).

PMID- 21968610
TI  - Histone H4 deacetylation down-regulates catalase gene expression in doxorubicin
      resistant AML subline.
AB  - We explored if epigenetic mechanisms could be involved in the down-regulated
      expression of catalase gene (CAT) in the doxorubicin-resistant acute myelogenous
      leukemia (AML)-2/DX100 cells. Down-regulated CAT expression in AML-2/DX100 cells
      was completely recovered after treatment of hydrogen peroxide (H(2)O(2)) and
      histone deacetylase inhibitor, trichostatin A (TSA) but was increased slightly by
      the treatment of DNA methylation inhibitor, 5-aza-2'-deoxycytidine (5-AdC).
      Bisulfite-sequencing PCR revealed that a CpG island of CAT was not methylated in
      AML-2/DX100 cells. Chromatin immunoprecipitation assay confirmed that acetylation
      of histone H4 in AML-2/DX100 cells significantly decreased as compared with that
      in AML-2/WT cells, which was significantly increased by TSA more than 5-AdC.
      Meanwhile, overexpression of other up-regulated peroxidase genes appears to make
      compensation for decreased H(2)O(2)-scavenging activity for the down-regulated
      CAT expression in AML-2/DX100 cells. These results suggest that histone H4
      deacetylation is responsible for the down-regulated CAT expression in AML-2/DX100
      cells, which are well adapted to oxidative stress.

PMID- 21968608
TI  - Evaluation of the ability of collagen-glycosaminoglycan scaffolds with or without
      mesenchymal stem cells to heal bone defects in Wistar rats.
AB  - PURPOSE: The aim of this experiment was to examine the capacity of collagen
      glycosaminoglycan scaffolds, with or without mesenchymal stem cells, to
      satisfactorily repair a 5-mm rat calvarial defect. METHODS: Fifty-five Wistar
      rats were used in the study. The defects were either left empty to serve as
      controls (n = 7) or filled with cell-free scaffolds (n = 11), cell-seeded
      scaffolds that were pre-cultured in standard culture medium (n = 13), cell-seeded
      scaffolds that were pre-cultured in osteoinductive factor-supplemented medium (n
      = 12) or particulate autogenous bone (n = 12). The animals were sacrificed at 12
      weeks after surgery, and specimens were prepared for histomorphometric analysis.
      The linear bone healing and the bone area within the defect were measured.
      RESULTS: Comparable results were obtained using cell-free collagen
      glycosaminoglycan scaffolds and autogenous bone both in terms of linear bone
      healing (P < 0.986) and area of new bone (P < 0.846). While the test groups
      showed significantly more bone formation compared to the empty defect control
      group, the linear bone healing and area of new bone within the defect were
      significantly lower in the cell-seeded scaffolds than in the cell-free scaffolds.
      The results have demonstrated that a cell-free collagen-glycosaminoglycan
      scaffold is capable of repairing a 5-mm rat calvarial defect as effectively as
      autogenous bone and that seeding the scaffold with pre-cultured mesenchymal stem
      cells prior to implantation offered no beneficial effect and resulted in
      incomplete healing of the defect. CONCLUSIONS: The results thus suggest that the
      scaffold has immense potential for tissue repair showing favorable
      osteoconductive properties, biocompatibility and degradability.

PMID- 21968611
TI  - Seasonal and diurnal patterns of spore release can significantly affect the
      proportion of spores expected to undergo long-distance dispersal.
AB  - Many of the fungal pathogens that threaten agricultural and natural systems
      undergo wind-assisted dispersal. During turbulent wind conditions, long-distance
      dispersal can occur, and airborne spores are carried over distances greater than
      the mean. The occurrence of long-distance dispersal is an important ecological
      process, as it can drastically increase the extent to which pathogen epidemics
      spread across a landscape, result in rapid transmission of disease to previously
      uninfected areas, and influence the spatial structure of pathogen populations in
      fragmented landscapes. Since the timing of spore release determines the wind
      conditions that prevail over a dispersal event, this timing is likely to affect
      the probability of long-distance dispersal occurring. Using a Lagrangian
      stochastic model, we test the effect of seasonal and diurnal variation in the
      release of spores on wind-assisted dispersal. Spores released during the hottest
      part of the day are shown to be more likely to undergo long-distance dispersal
      than those released at other times. Furthermore, interactions are shown to occur
      between seasonal and diurnal patterns of release. These results have important
      consequences for further modelling of wind-assisted dispersal and the use of
      models to predict the spread of fungal pathogens and resulting population and
      epidemic dynamics.

PMID- 21968613
TI  - The HVL in soft tissue and the AAPM and IEC exposure indices.
AB  - Manual exposure settings for radiographic projections were once based on a points
      system which assumed that the HVL in soft tissue is 3.0 cm and that each change
      of 1.0 cm of soft tissue corresponded to a change of 25% in image receptor dose.
      A set of mAs steps and equivalent kVp steps was estimated that would give
      appropriate technique factors for changes in patient thickness. With the advent
      of rare-earth screen-film systems and AEC systems the points system fell into
      disuse. Screen-film imaging systems have almost entirely been replaced by CR or
      DR systems and recently, standardised exposure indices have been recommended by
      the AAPM and IEC to provide exposure guidance for these systems. If the
      fundamental assumptions on which the points system was based are still valid for
      modern high-frequency generators and digital imaging systems, then there would be
      an elegant correspondence between the predictions of the points system and the
      requirements for correction of exposure errors indicated by the AAPM and IEC
      indices. This study estimated the HVL and attenuation per cm in soft tissue using
      computer simulation, finding that practically, the HVL is between 2.0 and 5.0 cm
      and attenuation per cm ranges from 15 to 25%. The study concluded that agreement
      between the points system predictions and the true effects of technique factors
      changes on dose to the image receptor was moderately good, that use of the points
      system and technique charts based on this system should be encouraged and that
      use of the IEC or AAPM digital exposure indices should be standardised.

PMID- 21968612
TI  - Inter-professional clinical practice guideline for vocational evaluation
      following traumatic brain injury: a systematic and evidence-based approach.
AB  - INTRODUCTION: This paper introduces an inter-professional clinical practice
      guideline for vocational evaluation following traumatic brain injury. This
      guideline aims to explicate the processes and factors relevant to vocational
      evaluation to assist evaluators (i.e. health care teams, individuals and
      employers) in collaboratively determining if clients are able to work and to make
      recommendations for work entry, re-entry or vocational planning. METHODS: Methods
      in the Canadian Medical Association's (CMA) Handbook on Clinical Practice
      Guideline and the Appraisal of Guidelines for Research and Evaluation (AGREE)
      instrument were utilized to ensure rigour. Steps in the CMA handbook were
      followed and included: (1) identifying the guideline's objective and questions;
      (2) systematic literature review; (3) study selection and quality appraisal; (4)
      development of clear recommendations by key stakeholders; (5) guideline pilot
      testing and endorsement. RESULTS: The resulting guideline includes 17 key
      recommendations within the seven domains: (1) evaluation purpose and rationale;
      (2) initial intake process; (3) assessment of the personal domain; (4) assessment
      of the environment; (5) assessment of occupational/job requirements; (6) analysis
      and synthesis; (7) evaluation recommendations. CONCLUSIONS: The guideline may be
      useful to individually practicing clinicians, health care teams, employers and
      individuals with TBI. Future research will formally examine the success of the
      guideline's implementation.

PMID- 21968614
TI  - Lack of backscatter factor measurements in HDR applications with MOSkins.
AB  - Measurements of backscatter correction factors for intra operative (IOBT) HDR
      brachytherapy applicators were made using Centre for Medical Radiation Physics
      (CMRP), MOSFET devices. In clinical use there is an absence of backscatter
      material above the IOBT applicator, leading to a lower dose than predicted by
      conventional TG-43 dose calculations. To estimate the uncertainty in the MOSFET
      measurements, the dosimetric characteristics, including reproducibility,
      stability, linearity, and angular and energy response were measured using a HDR
      Ir-192 source, kilovoltage treatment unit and a high energy linac. Measurements
      were compared with previously published Monte Carlo data. Variability of the
      response of the MOSFETs due to angular variation contributed the largest
      uncertainty in dose measurements. Using the IOBT applicator without adequate
      scatter material resulted in a reduction of delivered dose of on average 10%, but
      was dependent on the location on the applicator and the treatment field size.
      Theoretical calculations based on previously published study indicated an
      expected reduced dose of on average 4%. MOSFET devices provide an ideal
      measurement tool in the presence of high dose gradients, however, the dosimetric
      characteristics of the detector must be accounted for when estimating the
      uncertainty.

PMID- 21968615
TI  - Structural analysis of NADPH depleted bovine liver catalase and its inhibitor
      complexes.
AB  - To study the functional role of NADPH during mammalian catalase inhibition, the X
      ray crystal structures of NADPH-depleted bovine liver catalase and its inhibitor
      complexes, cyanide and azide, determined at 2.8A resolution. From the complex
      structures it is observed that subunits with and without an inhibitor/catalytic
      water molecule are linked by N-terminal domain swapping. Comparing mammalian- and
      fungal- catalases, we speculate that NADPH-depleted mammalian catalases may
      function as a domain-swapped dimer of dimers, especially during inactivation by
      inhibitors like cyanide and azide. We further speculate that in mammalian
      catalases the N-terminal hinge-loop region and alpha-helix is the structural
      element that senses NADPH binding. Although the above arguments are speculative
      and need further verification, as a whole our studies have opened up a new
      possibility, viz. that mammalian catalase acts as a domain-swapped dimer of
      dimers, especially during inhibitor binding. To generalize this concept to the
      formation of the inactive state in mammalian catalases in the absence of tightly
      bound NADPH molecules needs further exploration. The present study adds one more
      intriguing fact to the existing mysteries of mammalian catalases.

PMID- 21968617
TI  - Voluntary Counseling and Willingness to Screen among Nigerian Long Distance Truck
      Drivers.
AB  - BACKGROUND: Voluntary counseling and testing (VCT) is an important preventive
      strategy in the control of HIV/AIDS and Long distance truck drivers (LDTD) have
      been identified as an important group in the transmission of HIV/AIDS. This study
      aims to assess knowledge and perception of Nigerian long distance truck drivers
      on HIV/AIDS, voluntary counseling and testing and their willingness to undergo
      HIV screening.  MATERIALS AND METHODS: One hundred and ninety seven LDTD in
      Enugu, Nigeria were surveyed using pre tested structured questionnaires. 
      RESULTS: Awareness of HIV/AIDS was high (94.9%) amongst the drivers and the media
      was their commonest source of information. Similarly the awareness of VCT was
      high (94.4%). One hundred and eight (54.8%) respondents were willing to undergo
      HIV screening test if offered freely and 86 (43.7%) others have previously been
      screened. Educational status was a significant determinant of willingness to
      undergo HIV screening p<0.05. The reasons for screening were mainly doctors'
      recommendation (19.3%) and voluntary self screening (18.8%). The commonest
      reasons for not wanting to undergo screening were the feeling of not being at
      risk (27.9%), fear of a positive result (10.2%) and cost of screening test
      (9.6%).  CONCLUSION: There is a critical need to improve HIV screening
      participation amongst Long distance drivers in Nigeria.

PMID- 21968616
TI  - Potent inhibitory effect of the cyclolignan picropodophyllin (PPP) on human
      adrenocortical carcinoma cells proliferation.
AB  - Adrenocortical carcinoma (ACC) is a very aggressive tumor with a poor prognosis.
      Available treatments for this type of cancer are far from being satisfactory. The
      IGF signalling pathway represents an important mechanism for ACT growth and
      constitutes a relevant therapeutic target. We investigated the effect of
      picropodophyllin (PPP), a member of the cyclolignan family and a new inhibitor of
      IGF-1R, on proliferation of human adrenocortical cell lines H295R and SW-13. PPP
      inhibits proliferation and induces an important accumulation in G2/M phase and
      apoptosis of H295R and SW-13 cells. Our data suggest that PPP may be a promising
      candidate for drug development for adrenocortical carcinoma.

PMID- 21968618
TI  - Medication adherence in the asthmatic child and adolescent.
AB  - Asthma is a common inflammatory condition affecting more than 7 million children
      in the United States alone, and tens of millions more globally. Despite effective
      preventive medications, medication nonadherence in children and adolescents is
      alarmingly high. Nonadherence can result in poor asthma control, which leads to
      decreased quality of life, lost productivity, increased health care utilization,
      and even the risk of death. Nonadherence in children and adolescents deserves
      special attention because they face unique barriers to adherence that change with
      age. Young children depend on adults for the delivery of asthma care, and their
      care is strongly influenced by parental motivation and attitudes and the home
      environment. As these children enter adolescence, they typically assume
      responsibility for their asthma care at the same time that they are claiming
      their independence and possibly experimenting with high-risk behaviors. Morbidity
      and mortality, as well as nonadherence, appear to be greatest among adolescents
      and minority children. Although no perfect tool for measuring adherence exists,
      objective methods, such as electronic monitoring, can provide valuable
      information to health care providers. Beyond asthma self-management and
      education, no specific resource-heavy adherence interventions have proven
      consistently helpful. However, large-scale, well-designed studies on this subject
      are lacking. In light of the fact that nonadherence is a potentially modifiable
      factor that impacts on morbidity and mortality, it is worth pursuing further
      research to determine better interventions. It is likely, however, that no one
      answer exists, and interventions will need to be tailored to specific at-risk
      populations.

PMID- 21968620
TI  - Response to treatment with imatinib mesylate in previously treated chronic-phase
      chronic myeloid leukemia patients in a hospital in Brazil.
AB  - We  analyzed the results of treatment with imatinib mesylate in 70 patients with 
      chronic-phase chronic myeloid leukemia who had previously been treated (with 
      second-line or higher imatinib), many of them in a late chronic phase. The 
      median follow-up period was 60.5 months (range 3-100 months). Our objective was 
      to assess the efficacy and safety of treatment. The mean dose was 400 mg per 
      day. The hematologic response rate was 92.1% at six months, while the  cumulative
      rates of major and complete cytogenetic responses were 73.6 and  66.3%,
      respectively. Molecular response rate improved slowly and steadily over  time,
      reaching 65.8% at 60 months, remaining stable for up to 96 months. The  five-year
      progression-free survival and overall survival were 84 and 89%,  respectively.
      Cytogenetic response by 12 months significantly correlated with  overall survival
      (P = 0.0007) and progression-free survival (P = 0.0280). Sokal  risk score did
      not differ significantly between subgroups. The medication was  well tolerated,
      with only 16% of patients showing hematologic toxicity grades 3  and 4. At the
      end of the assessment, 57% of the patients were still on imatinib  mesylate; most
      of those who discontinued treatment (17/30) did so because of  unsatisfactory
      response. Treatment with imatinib mesylate in previously treated  chronic-phase
      chronic myeloid leukemia induced durable responses in a high  proportion of
      patients and was related to satisfactory long-term and event-free  survival.

PMID- 21968621
TI  - Comparative genetic analysis of trichome-less and normal pod genotypes of Mucuna
      pruriens (Fabaceae).
AB  - Velvet  bean (Mucuna pruriens) seeds contain the catecholic amino acid L-DoPA  (L
      3,4-dihydroxyphenylalanine), which is a neurotransmitter precursor and used  for
      the treatment of Parkinson's disease and mental disorders. The great demand  for
      L-DoPA is largely met by the pharmaceutical industry through extraction of  the
      compound from wild populations of this plant; commercial exploitation of  this
      compound is hampered because of its limited availability. The trichomes  present
      on the pods can cause severe itching, blisters and dermatitis,  discouraging
      cultivation. We screened genetic stocks of velvet bean for the  trichome-less
      trait, along with high seed yield and L-DoPA content. The highest  yielding
      trichome-less elite strain was selected and indentified on the basis  of a PCR
      based DNA fingerprinting method (RAPD), using deca-nucleotide primers.  A genetic
      similarity index matrix was obtained through multivariant analysis  using Nei and
      Li's coefficient. The similarity coefficients were used to  generate a tree for
      cluster analysis using the UPGMA method. Analysis of  amplification spectra of
      408 bands obtained with 56 primers allowed us to  distinguish a trichome-less
      elite strain of M. pruriens.

PMID- 21968622
TI  - Single nucleotide polymorphisms in CAPN and leptin genes associated with meat
      color and tenderness in Nellore cattle.
AB  - We analyzed single nucleotide polymorphisms in  calpain, leptin, leptin receptor,
      and growth hormone receptor genes and their  association with color, drip and
      cooking losses of longissimus muscle at 7, 14  and 21 days postmortem in 638
      purebred Nellore bulls slaughtered between 22 and  26 months of age. Meat samples
      were vacuum-packed and aged at 4 degrees C. The single  nucleotide polymorphisms
      T945M, GHR2, E2FB, and CAPN4751 were evaluated. All  genotypic classes were
      observed; however, the T/T genotype of T945M and E2FB  was found at a low
      frequency. A significant association of E2FB with drip loss  (a measure of water
      holding capacity) was detected at seven days of meat aging.  CAPN4751 had an
      additive effect on red and yellow color intensities. The T  allele of CAPN4751
      was found to be positively associated with improved meat  color, but not with
      meat tenderness, differing from a previous report  indicating that it is
      associated with meat tenderness. We conclude that the  potential for use of
      CAPN4751 as a marker for these meat quality traits  requires further research.

PMID- 21968623
TI  - Isolation and characterization of microsatellite markers for the Korean rockfish,
      Sebastes schlegeli.
AB  - The Korean rockfish (Sebastes schlegeli) is an  important commercial fish that is
      widely used in aquaculture. We isolated and  characterized 18 polymorphic
      microsatellite loci from the Korean rockfish using  a (GT)(13)-enriched  genomic
      library. Polymorphism was assessed in 48 individuals from a single  population
      collected from the northern coastal waters of the Yellow Sea. The  observed and
      expected heterozygosities ranged from 0.0244 to 0.7660 (mean  0.4194) and 0.0244
      to 0.8758 (mean 0.5002), respectively. Polymorphism at these  loci indicated from
      two to 15 alleles (mean 5.7); 14 of 18 loci conformed to  Hardy-Weinberg
      equilibrium. These markers should be useful for management and  conservation
      studies of this species.

PMID- 21968624
TI  - A novel SNP of the C/EBPalpha gene associated with superior meat quality in
      indigenous Chinese cattle.
AB  - CCAAT/enhancer-binding  protein alpha (C/EBPalpha) is an essential
      transcriptional factor regulating the  differentiation of adipocytes. We report a
      novel single nucleotide polymorphism  (C271A) of the C/EBPalpha gene in six
      indigenous Chinese cattle breeds using  PCR-SSCP and DNA sequencing methods.
      Allele frequencies were investigated and  evaluated by the chi(2) test in  817
      individuals; all populations were found to be in Hardy-Weinberg  equilibrium.
      Gene heterozygosity, effective allele numbers and polymorphism  information
      content of the C/EBPalpha locus varied from 0.50 to 0.54, 1.84 to 1.99  and 0.35
      to 0.37, respectively. We also evaluated a potential association of  the
      C/EBPalpha SNP with ultrasound traits in 555 individuals; individuals of the AA 
      genotype had greater ultrasound backfat thickness than did genotype CC (0.36 
      versus 0.34 cm, P < 0.01); genotypes AA and CA had higher ultrasound marbling 
      scores than did genotype CC (3.53, 3.52 versus 3.37, P < 0.05). Analysis  based
      on meat quality data in another 204 Qinchuan cattle showed that animals  with
      genotype AA had bigger loin eye areas than did genotype CA (87.10 versus  79.08
      cm(2), P < 0.05). These results indicate  that the C271A SNP of the C/EBPalpha
      gene could be used as a molecular marker for  selecting beef cattle with superior
      carcass traits.

PMID- 21968625
TI  - Morphometric and molecular analysis of mackerel (Rastrelliger spp) from the west
      coast of Peninsular Malaysia.
AB  - Mackerel  (Scombridae; Rastrelliger) are small commercially important pelagic 
      fish found in tropical regions. They serve as a cheap source of animal protein 
      and are commonly used as live bait. By using a truss morphometrics protocol and 
      RAPD analysis, we examined morphological and genetic variation among 77 
      individual mackerel that were caught using long lines and gillnets at 11 
      locations along the west coast of Peninsular Malaysia. Nineteen morphometric 
      traits were evaluated and genetic information was estimated using five 10-base 
      RAPD random primers. Total DNA was extracted from muscle tissue. Morphometric 
      discriminant function analysis revealed that two morphologically distinct  groups
      of Rastrelliger kanagurta and a single group of R. brachysoma can  be found along
      the west coast of Peninsular Malaysia. We also found that the  head-related
      characters and those from the anterior part of the body of Rastrelliger spp
      significantly contribute to stock assessment of this population. RAPD  analysis
      showed a trend similar to that of the morphometric analysis,  suggesting a
      genetic component to the observed phenotypic differentiation.  These data will be
      useful for developing conservation strategies for these  species.

PMID- 21968626
TI  - [Deep Oscillation: therapeutic-rehabilitative experiences with a new
      electrostatic device].
AB  - AIM: Deep Oscillation(r) is an apparatus that produces low frequency
      electromagnetic radiations able to modulate immune reactions and, therefore,
      applicable to pain, tumour and inflammation treatments. The aim of this study is
      to evaluate how the Deep Oscillation(r) therapy works on conventional therapy
      resistant patients as the apparatus can be applied either to trauma derived fom
      surgical wounds or on sports post-traumatic oedema, low back pain and/or
      sciatalgic pain and cervicobrachial pain. METHODS: In the first part of the
      study, 34 cases of recent surgical wounds have been treated with Deep
      Oscillation(r) with 3 times a week visits for 20 minutes. In the same way 30
      cases of sports post-traumatic oedema, 20 cases of low back pain and/or
      sciatalgic pain and 10 cases of cervicobrachial pain were treated. Among these
      patients, 15 cases had also undergone contemporaneous nonsteroidal anti
      inflammatory drugs intravenous drip, electrolytes and vitamins to verify the
      probable synergetic efficacy of both treatments. RESULTS: The results confirm
      that in some cases the Deep Oscillation(r) treatment is effective since the
      first/third therapy up to the restitutio ad integrum. It has also been
      demonstrated that the maximum efficiency of the Deep Oscillation(r) and
      nonsteroidal anti-inflammatory drugs synergetic treatment is probably due to the
      electromagnetic radiations able to facilitate the pharmacological uptake.
      CONCLUSION: This study confirms the capacity of the electrostatic energy,
      released by Deep Oscillation(r), to stimulate the patient's neurosensory system,
      raising his pain threshold and facilitating his pharmacological uptake and
      restoring his functional recovery more quickly.

PMID- 21968627
TI  - Multiple relaxation processes versus the fragile-to-strong transition in confined
      water.
AB  - Broadband dielectric spectroscopy data on water confined in three different
      environments, namely at the surface of a globular protein or inside the small
      pores of two silica substrates, in the temperature range 140 K <= T <= 300 K, are
      presented and discussed in comparison with previous results from different
      techniques. It is found that all samples show a fast relaxation process,
      independently of the hydration level and confinement size. This relaxation is
      well known in the literature and its cross-over from Arrhenius to non-Arrhenius
      temperature behavior is the object of vivid debate, given its claimed relation to
      the existence of a second critical point of water. We find such a cross-over at a
      temperature of ~180 K, and assign the relaxation process to the layer of
      molecules adjacent and strongly interacting with the substrate surface. This is
      the water layer known to have the highest density and slowest translational
      dynamics compared to the average: its apparent cross-over may be due to the
      freezing of some degree of freedom and survival of very localized motions alone,
      to the onset of finite size effects, or to the presence of a calorimetric glass
      transition of the hydration shell at ~170 K. Another relaxation process is
      visible in water confined in the silica matrices: this is slower than the
      previous one and has distinct temperature behaviors, depending on the size of the
      confining volume and consequent ice nucleation.

PMID- 21968628
TI  - Gender differences in UV-induced inflammation and immunosuppression in mice
      reveal male unresponsiveness to UVA radiation.
AB  - Immunosuppression attributed mainly to the UVB (290-320 nm) waveband is a
      prerequisite for skin cancer development in mice and humans. The contribution of
      UVA (320-400 nm) is controversial, but in mice UVA irradiation has been found to
      antagonise immunosuppression by UVB. In other studies of photoimmune regulation,
      protection mediated via oestrogen receptor-beta signalling was identified as a
      normal endogenous defence in mice, and was shown to depend on UVA irradiation. A
      gender bias in photoimmune responsiveness was thus suggested, and is tested in
      this study by comparing the UV-induced inflammatory and immune responses in male
      and female hairless mice. We report that male mice, which show greater skin
      thickness than females, developed a less intense but slower resolving sunburn
      inflammatory oedema, correlated with reduced epidermal expression of pro
      inflammatory IL-6 than females following solar simulated UV (SSUV, 290-400 nm)
      exposure. On the other hand, the contact hypersensitivity reaction (CHS) was more
      severely suppressed by SSUV in males, correlated with increased epidermal
      expression of immunosuppressive IL-10. Exposure to the UVB waveband alone, or to
      cis-urocanic acid, suppressed CHS equally in males and females. However, whereas
      UVA irradiation induced immunoprotection against either UVB or cis-urocanic acid
      in females, this protection was significantly reduced or abrogated in males. The
      results indicate that males are compromised by a relative unresponsiveness to the
      photoimmune protective effects of UVA, alone or as a component of SSUV. This
      could explain the known gender bias in skin cancer development in both mice and
      humans.

PMID- 21968629
TI  - Internet and e-mail use in ENT: a survey of patient usage and satisfaction.
AB  - Nowadays, internet and e-mail are important modes of communication and
      information. This paper seeks to determine internet usage as a source of health
      information amongst ENT patients and to investigate whether patients prefer to
      communicate primarily with the hospital via e-mail. The method used is a
      questionnaire study and 201 patients attending an ENT clinic completed
      questionnaires over 2 weeks in December 2010. Of those with internet access
      (85%), 37% had used it for health information prior to their appointment; 90%
      rated the information between average and excellent; over half stated they would
      like doctor-recommended websites. Overall, 8% had previously used e-mail to
      communicate with healthcare professionals, but 50% stated that they wished to use
      e-mail in the future. ENT patients are becoming increasingly computer-literate.
      As healthcare professionals, we must do more to incorporate the internet as a
      source of reliable healthcare information. Properly implemented, e-mail can
      become an invaluable method of communication with patients.

PMID- 21968630
TI  - Audiological and graft take results of cartilage reinforcement tympanoplasty (a
      new technique) versus fascia.
AB  - Our objective is to compare hearing and graft take results of temporal muscle
      fascia tympanoplasty and cartilage reinforcement tympanoplasty. Seventy seven
      patients are classified into two groups: Group 1 included 37 patients for whom
      cartilage graft, harvested from symba concha, is used as reinforcement under
      temporalis muscle fascia anteriorly and Group 2 included 40 patients for whom
      only temporalis muscle fascia is used in type 1 tympanoplasty. A pure-tone
      audiometry is done within 1 week prior to surgery and at 6 months
      postoperatively. There is statistically significant difference between
      postoperative graft take results among groups. In both groups postoperative
      anterior TM perforation is encountered most commonly. Success rate of cartilage
      reinforcement tympanoplasty in revision patients is 100% but temporal muscle
      fascia tympanoplasty's is 66%. There is no statistically significant difference
      between preoperative and postoperative air conduction gain of TM intact patients.
      The results indicated that Cartilage reinforcement myringoplasty technique under
      anterior of the temporal muscle fascia significantly increases the graft take
      ratios in high-risk perforations and it also does not affect hearing levels.
      Therefore, the authors suggest usage of cartilage reinforcement tympanoplasty
      technique under anterior of the temporal muscle fascia which is an easy and
      applicable technique to increase graft take ratios, particularly in patients with
      preoperative anterior and subtotal TM perforations.

PMID- 21968631
TI  - Preliminary proteomic analysis of human serum from patients with laryngeal
      carcinoma.
AB  - To better evaluate the serum protein alterations in patients with laryngeal
      carcinoma during surgical treatment process, a comparative proteomic analysis of
      human serum from patients with laryngeal carcinoma between pre- and post
      operation group was performed using two-dimensional gel electrophoresis, in
      combination with matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry and database searching. Statistical analysis indicated that 16 gel
      spots corresponding to 12 proteins altered their expression significantly between
      the two groups of patients with laryngeal carcinoma. Of these 12 proteins, 6
      proteins were up-regulated in the pre-operation group. The subsequent Western
      blot confirmed the results of proteome analysis. Measurement of MDA and SOD
      levels in serum combining with bioinformatics analysis indicated the potential
      roles of the oxidant stress and immune response as target in monitoring and
      treating laryngeal carcinoma. The study provides new insight into the laryngeal
      carcinoma development and treatment, and the identified proteins are warranted to
      be further studied.

PMID- 21968632
TI  - Use of flexible CO2 laser fiber in microsurgery for vestibular schwannoma via the
      middle cranial fossa approach.
AB  - The aim of this study was to analyze the results of microsurgery in vestibular
      schwannomas (VS) with assistance of a flexible CO(2) laser fiber (Omniguide((r)))
      using the middle cranial fossa (MCF) approach. For that purpose we performed a
      prospective non-randomized clinical trial. In 20 consecutive patients suffering
      from VS and elected for microsurgery via the MCF approach, tumor resection was
      performed with the aid of the flexible CO(2) laser ("laser group", LG). Twenty
      patients with similar tumor volume and pre-operative hearing status out of a
      cohort of 76 patients previously treated by the same surgeon without laser were
      used as comparison group ("conventional group", CG) (matched-pair-technique).
      Facial weakness (House-Brackmann (HB) 2-4) was seen in early postoperative (p.o.)
      days in six patients in each group and all recovered completely by 3 months p.o.,
      except one patient with HB 2 in CG. Facial nerve preservation rate (HB 1 + 2) was
      100% in both groups. Hearing preservation rate (Gardner/Robertson class 1 + 2 or
      AAO-HNS A + B, pre- and postoperatively) was 72% in LG and 82% in CG, without
      significant difference. Overall time from incision to skin suture was 157 min (SD
      55.9) in CG and 160 min (SD 39.7) in LG. Tumor preparation time was 23.2 min (SD
      19.7) in CG and 36.1 min (SD 33.8) in LG. The use of a handheld flexible CO(2)
      laser fiber in VS-microsurgery is safe and subjectively facilitates tumor
      resection especially in "difficult" (e.g., highly vascularized) tumors. However,
      in this limited prospective trial the excellent functional outcome following
      conventional microsurgery could not be further improved, nor the surgical time
      reduced by means of the non-contact laser-tool. Focusing the use of the flexible
      CO(2) laser on "difficult" tumors may lead to different results in future.

PMID- 21968633
TI  - An unusual case of anterior and posterior laryngeal cleft together: combined
      cleft of larynx.
AB  - Congenital clefts of the larynx are rare and usually found dorsally. An anterior
      or ventral cleft of the larynx is extremely rare. Only a few patients with this
      defect have been reported in the literature. The purpose of this paper is to
      present a patient having an anterior and posterior laryngeal cleft together. A 20
      year-old man presented with a history of dysphonia since childhood. He did not
      report symptoms of swallowing or respiration, and had no history of neck trauma.
      Findings of videolaryngoscopy showed a grossly abnormal larynx. The anterior
      commissure was wider than normal, and the vocal folds did not show a fusion
      anteriorly. There was an interarytenoid cleft posteriorly. A neck CT with 3D
      reconstruction demonstrated a ventral cleft or nonfusion of the thyroid cartilage
      with a posterior cricoid cleft. Barium swallow study was in normal limits. Since
      the patient did not have any problem with swallowing or respiration, no surgical
      intervention was planned, and the patient was put on speech therapy, which
      revealed improvement in voice. To our knowledge, this is the first case of a
      combined laryngeal cleft. The diagnosis is established by the clinical symptoms,
      endoscopic evaluation, and radiographic examinations including 3D and barium
      studies.

PMID- 21968635
TI  - The comparative study of video laryngoscopes to the Macintosh laryngoscope: 
      defining proficiency is critical.

PMID- 21968637
TI  - What limits the effect of lipid emulsion therapy?

PMID- 21968636
TI  - Non-adherence to guidelines for preoperative testing in a secondary care hospital
      in Austria:  the economic impact of unnecessary and double testing.
AB  - CONTEXT: Preoperative evaluation is aimed at prevention of complications and risk
      stratification. Routine testing should be abandoned in favour of selective
      ordering according to contemporary guidelines. This study was conducted to
      calculate the possible economic impact of a Web-based preoperative diagnostic
      guideline prior to its implementation in the state of Salzburg, Austria. DESIGN:
      Prospective observational cohort study. SETTING: The study was carried out in a
      secondary care hospital in Salzburg (Schwarzach). PARTICIPANTS AND MAIN OUTCOME
      MEASURES: Data from 1363 consecutive patients scheduled for elective surgery from
      1 September to 30 November 2007 were collected: demographic data, medical
      history, surgical procedure, preoperative tests and findings. The data were
      entered into the preoperative diagnostic guideline software and the guideline
      adherent recommendations were compared with the investigations performed, with
      special attention to duplicate examinations. RESULTS: A total of 5879 tests were
      documented and analysed. In 65.6% of patients, guideline-adherent evaluation
      would have indicated only basic requirements, but 3380 additional tests were
      carried out. In all, 81.7% of tests were identified as nonadherent based on the
      preoperative diagnostic guideline software and 226 duplicate tests were
      performed. Possible savings per 1000 patients would be ?26  287 if preoperative
      diagnostic guideline recommendations were followed exactly and ?1076 if
      duplicated tests were avoided. According to a generalised linear model (Gamma
      model), an increase of 1 year of age leads to an increase of costs by a factor of
      1.020. CONCLUSION: These data indicate a considerable potential for improvement
      in process quality and cost reduction by using structured preoperative assessment
      with computer-assisted implementation of a guideline.

PMID- 21968638
TI  - Dantrolene for severe rhabdomyolysis in Staphylococcus aureus toxic shock
      syndrome.

PMID- 21968640
TI  - Alexithymic traits and facial emotion recognition in borderline personality
      disorder.

PMID- 21968641
TI  - A case of choroid plexus papilloma with stromal sclerosis and indistinct
      papillary structures.
AB  - We present a case of choroid plexus papilloma with unusual histopathological
      findings. A 41-year-old Japanese man presented with dizziness. Brain magnetic
      resonance imaging scan showed a distinct mass in the fourth ventricle.
      Histopathological examination showed proliferation of cuboidal cells forming
      irregular trabeculae, small nests, and pseudoglandular and indistinct papillary
      structures, accompanied by a variable degree of stromal sclerosis. The tissue
      sections also showed rare mitotic activity, no hypercellularity, cellular
      pleomorphism, or necrosis. The immunohistochemical findings were tumor cells
      positive for cytokeratin 7, vimentin, S-100 protein, and transthyretin but
      negative for cytokeratin 20, BerEP4 and carcinoembryonic antigen. These findings
      were consistent with choroid plexus papilloma. The combination of these
      immunohistochemical markers was helpful in establishing the diagnosis, although
      the morphological finding of stromal sclerosis is rare for choroid plexus
      papilloma.

PMID- 21968643
TI  - Cutaneous magnetic stimulation reduces rat chronic pain via activation of the
      supra-spinal descending pathway.
AB  - Recent studies have demonstrated that magnetic stimulation (MS) can induce
      cellular responses such as Ca(2+) influx into the cultured neurons and glia,
      leading to increased intracellular phosphorylation. We have demonstrated
      previously that MS reduces rat neuropathic pain associated with the prevention of
      neuronal degeneration. Thus, we aimed to elucidate the actions of MS in relation
      to modulation of spinal neuron-glia and the descending inhibitory system in
      chronic pain. The male SD rats intrathecally implanted with catheters were
      subjected to sciatic nerve ligation (CCI). MS is a low power apparatus
      characterized by two different frequencies, 2 KHz and 83 MHz. Rats were given MS
      to the skin (injured sciatic nerve) for 10 min from the seventh day after CCI.
      The paw withdrawal latency (PWL) evoked by thermal stimuli was measured for 14
      days after CCI. Immunohistochemistry for Iba-1 or GFAP was performed after 4%
      paraformaldehyde fixation (microscopic analysis). We employed microdialysis for
      measuring CSF 5-HIAA as a reflection of 5-HT release by MS stimulation. Following
      CCI, rats showed a decrease in PWL after CCI, and the decrease continued until
      the 14th day. With MS treatment, the decrease in PWL was reduced during the 10-14
      day after CCI. Injection of JNK-1 inhibitors on the 14th day antagonized the
      analgesic effect of MS. MS also eliminated the CCI-induced decrease in GFAP
      immunoreactivity. Moreover, MS evoked spinal 5-HT release reflected by increase
      in spinal 5-HIAA level. Thus, we demonstrate that a novel magnetic stimulator
      used cutaneously can ameliorate chronic pain by not only preventing abnormal
      spinal neuron-glia interaction, but also through the activation of the supra
      spinal descending inhibitory system.

PMID- 21968642
TI  - Donepezil in a narrow concentration range augments control and impaired by beta
      amyloid peptide hippocampal LTP in NMDAR-independent manner.
AB  - Acetylcholinesterase (AChE) inhibitor donepezil is widely used for the treatment
      of Alzheimer's disease (AD). The mechanisms of therapeutic effects of the drug
      are not well understood. The ability of donepezil to reverse a known pathogenic
      effect of beta-amyloid peptide (Abeta), namely, the impairment of hippocampal
      long-term potentiation (LTP), was not studied yet. The goal of the present study
      was to study the influence of donepezil in 0.1-10 MUM concentrations on control
      and Abeta-impaired hippocampal LTP. Possible involvement of N-methyl-D: 
      aspartate receptors (NMDARs) into mechanisms of donepezil action was also
      studied. LTP of population spike (PS) was studied in the CA1 region of rat
      hippocampal slices. Change of LTP by donepezil treatment had a bell-shaped dose
      response curve. The drug in concentrations of 0.1 and 1 MUM did not change LTP
      while in concentration of 0.5 MUM significantly increased it, and in
      concentration of 5 and 10 MUM suppressed LTP partially or completely. Abeta (200
      nM) markedly suppressed LTP. Addition of 0.1, 0.5 or 1 MUM donepezil to Abeta
      solution caused a restoration of LTP. N-methyl-D: -aspartate (NMDA) currents were
      studied in acutely isolated pyramidal neurons from CA1 region of rat hippocampus.
      Neither Abeta, nor 0.5 MUM donepezil were found to change NMDA currents, while 10
      MUM donepezil rapidly and reversibly depressed it. Results suggest that donepezil
      augments control and impaired by Abeta hippocampal LTP in NMDAR-independent
      manner. In general, our findings extend the understanding of mechanisms of
      therapeutic action of donepezil, especially at an early stage of AD, and maybe
      taken into account while considering the possibility of donepezil overdose.

PMID- 21968644
TI  - Existence of tenascin-C isoforms in rat that contain the alternatively spliced
      AD1 domain are developmentally regulated during hippocampal development.
AB  - Tenascin-C (TN-C) is a multimodular glycoprotein of the extracellular matrix
      which is important for the development of the nervous system and has a range of
      different functions which are mediated by the different protein domains present.
      TN-C contains eight constitutive fibronectin type III (FNIII) domains and a
      region of alternatively spliced FNIII domains. In the mouse and chick, six of
      these domains have been described and characterized, whereas in human there are
      nine of them. In this report, we show that seven alternatively spliced FNIII
      domains exist in rat and describe the differential expression pattern of the
      additional domain AD1 during embryonic and postnatal rat brain development. The
      AD1 domain of rat is homologous to the ones described in human and chick proteins
      but does not exist in mouse. Its expression can be located to the developing rat
      hippocampus and the lining of the lateral ventricle, regions where the TN-C
      protein may affect the behavior of stem and progenitor cells. During hippocampal
      development AD1 and the other alternatively spliced domains are differentially
      expressed as shown by RT-PCRs, immunocytochemistry and in situ hybridizations.

PMID- 21968645
TI  - Dietary nitrates, nitrites, and cardiovascular disease.
AB  - Dietary nitrate (NO(3)), nitrite (NO(2)), and arginine can serve as sources for
      production of NO(x) (a diverse group of metabolites including nitric oxide,
      nitrosothiols, and nitroalkenes) via ultraviolet light exposure to skin,
      mammalian nitrate/nitrite reductases in tissues, and nitric oxide synthase
      enzymes, respectively. NO(x) are responsible for the hypotensive, antiplatelet,
      and cytoprotective effects of dietary nitrates and nitrites. Current regulatory
      limits on nitrate intakes, based on concerns regarding potential risk of
      carcinogenicity and methemoglobinemia, are exceeded by normal daily intakes of
      single foods, such as soya milk and spinach, as well as by some recommended
      dietary patterns such as the Dietary Approaches to Stop Hypertension diet. This
      review includes a call for regulatory bodies to consider all available data on
      the beneficial physiologic roles of nitrate and nitrite in order to derive
      rational bases for dietary recommendations.

PMID- 21968646
TI  - Reduced susceptibility of Moritella profunda dihydrofolate reductase to
      trimethoprim is not due to glutamate 28.
AB  - The E28D variant of dihydrofolate reductase from Moritella profunda was generated
      and found to have the same K (i) (within error) for the competitive inhibitor
      trimethoprim as the wild type enzyme. Contrary to a previous claim in the
      literature, Glu 28 is therefore not the cause of the reduced affinity for
      trimethoprim relative to dihydrofolate reductase from Escherichia coli.

PMID- 21968647
TI  - PAQR10 and PAQR11 mediate Ras signaling in the Golgi apparatus.
AB  - Ras plays a pivotal role in many cellular activities, and its subcellular
      compartmentalization provides spatial and temporal selectivity. Here we report a
      mode of spatial regulation of Ras signaling in the Golgi apparatus by two highly
      homologous proteins PAQR10 and PAQR11 of the progestin and AdipoQ receptors
      family. PAQR10 and PAQR11 are exclusively localized in the Golgi apparatus.
      Overexpression of PAQR10/PAQR11 stimulates basal and EGF-induced ERK
      phosphorylation and increases the expression of ERK target genes in a dose
      dependent manner. Overexpression of PAQR10/PAQR11 markedly elevates Golgi
      localization of HRas, NRas and KRas4A, but not KRas4B. PAQR10 and PAQR11 can also
      interact with HRas, NRas and KRas4A, but not KRas4B. The increased Ras protein at
      the Golgi apparatus by overexpression of PAQR10/PAQR11 is in an active state.
      Consistently, knockdown of PAQR10 and PAQR11 reduces EGF-stimulated ERK
      phosphorylation and Ras activation at the Golgi apparatus. Intriguingly, PAQR10
      and PAQR11 are able to interact with RasGRP1, a guanine nucleotide exchange
      protein of Ras, and increase Golgi localization of RasGRP1. The C1 domain of
      RasGRP1 is both necessary and sufficient for the interaction of RasGRP1 with
      PAQR10/PAQR11. The simulation of ERK phosphorylation by overexpressed
      PAQR10/PAQR11 is abrogated by downregulation of RasGRP1. Furthermore,
      differentiation of PC12 cells is significantly enhanced by overexpression of
      PAQR10/PAQR11. Collectively, this study uncovers a new paradigm of spatial
      regulation of Ras signaling in the Golgi apparatus by PAQR10 and PAQR11.

PMID- 21968648
TI  - Expression of Y-Box-binding protein 1 in Chinese patients with breast cancer.
AB  - The purpose of this study was to investigate the expression of Y-Box-binding
      protein 1 (YB-1) in breast cancer and its correlation with clinicopathological
      characteristics and prognosis. Paraffin sections were retrospectively collected
      from 239 cases of stage I-III breast cancer patients and 30 healthy females who
      received surgery between January 2000 and December 2004 in the Chinese People's
      Liberation Army General Hospital. The protein expression of YB-1 was detected by
      immunohistochemistry. The expression difference between the two groups and the
      correlation between YB-1 expression and clinicopathological characteristics and
      breast cancer prognosis were analyzed. Within the breast cancer group, YB-1 was
      expressed in the cytoplasm in 100.0% (239/239) of cases and in the nucleus in
      36.8% (88/239) of cases. Within the control group of normal breast tissue, YB-1
      was expressed in the cytoplasm in 100.0% (30/30) of cases and in the nucleus in
      16.7% (5/30) of cases. The expression of YB-1 in the nucleus of breast cancer
      cells was significantly higher than that in normal breast tissue (P = 0.029). The
      expression of YB-1 in the nucleus of breast cancer cells positively correlated
      with the Scarff-Bloom-Richardson grade (P = 0.007) and HER-2 expression (P =
      0.005), negatively correlated with ER expression (P = 0.004), and was independent
      of the age, menstrual status, pathological type, tumor size, lymph node status,
      presence of thrombosis, PR expression, and EGFR expression. The 5-year disease
      free survival (DFS) and overall survival (OS) of patients with positive YB-1
      expression in the nucleus were significantly lower than those of patients who
      were negative for nuclear YB-1 expression, and the difference was statistically
      significant (DFS 65.9% vs. 82.1%, P = 0.000; OS 79.5% vs. 92.1%, P = 0.000).
      Multivariate analysis suggested that the expression of YB-1 in the nucleus is an
      independent prognostic factor that affects DFS and OS in breast cancer patients
      (DFS P = 0.015; OS P = 0.035). In conclusion, the expression of YB-1 in the
      nucleus is related to carcinogenesis and the development of breast cancer.
      Therefore, YB-1 is an important molecular marker that can be used to predict
      breast cancer prognosis.

PMID- 21968650
TI  - The gene expression profile of phosphoantigen-specific human gammadelta T
      lymphocytes is a blend of alphabeta T-cell and NK-cell signatures.
AB  - Global transcriptional technologies have revolutionised the study of lymphoid
      cell populations, but human gammadelta T lymphocytes specific for phosphoantigens
      remain far less deeply characterised by these methods despite the great
      therapeutic potential of these cells. Here we analyse the transcriptome of
      circulating TCRVgamma(+)  gammadelta T cells isolated from healthy individuals,
      and their relation with those from other lymphoid cell subsets. We report that
      the gene signature of phosphoantigen-specific TCRVgamma(+)  gammadelta T cells is
      a hybrid of those from alphabeta T and NK cells, with more 'NK-cell' genes than
      alphabeta T cells have and more 'T-cell' genes than NK cells. The expression
      profile of TCRVgamma(+)  gammadelta T cells stimulated with phosphoantigen
      recapitulates their immediate physiological functions: Th1 cytokine, chemokine
      and cytotoxic activities reflect their high mitotic activity at later time points
      and do not indicate antigen-presenting functions. Finally, such hallmarks make
      the transcriptome of gammadelta T cells, whether resting or clonally expanding,
      clearly distinctive from that of NK/T or peripheral T-cell lymphomas of the
      gammadelta subtype.

PMID- 21968651
TI  - PLA/ beta-TCP complex tubes: the mechanical properties and applications of
      artificial bone.
AB  - Poly(lactic acid) (PLA) twisted yarn was braided into a 6-layered, hollow,
      cylindrical braid on a 16-spindle braid machine. The PLA braid was then placed
      inside a beta-TCP tube, forming the PLA/beta-TCP complex tube which imitates the
      porous structure of sponge bone. Different components and structures were studied
      to determine the best bone molding material. The beta-TCP tube was created by
      sintering TCP powder mixed with stearic acid in a ratio of 1:1.5 to form a highly
      porous and well-structured tube with interconnected pores; its resulting porosity
      was 85.8 +/- 0.93%. The PLA/beta-TCP complex tube was implanted in a rabbit's
      femur and after 3 months a marrow cavity was discovered at the tube's core. New
      bone was also observed, regenerating around the PLA braid within the PLA/beta-TCP
      complex tube. 

PMID- 21968652
TI  - Heterologous expression and biochemical characterization of novel pyranose 2
      oxidases from the ascomycetes Aspergillus nidulans and Aspergillus oryzae.
AB  - A gene encoding a pyranose 2-oxidase (POx; pyranose/oxygen 2-oxidoreductase;
      glucose 2-oxidase; EC 1.1.3.10) was identified in the genome of the ascomycete
      Aspergillus nidulans. Attempts to isolate POx directly from A. nidulans cultures
      or to homologously overexpress the native POx (under control of the constitutive
      gpdA promoter) in A. nidulans were unsuccessful. cDNA encoding POx was
      synthesized from mRNA and expressed in Escherichia coli, and the enzyme was
      subsequently purified and characterized. A putative pyranose 2-oxidase-encoding
      gene was also identified in the genome of Aspergillus oryzae. The coding sequence
      was synthetically produced and was also expressed in E. coli. Both purified
      enzymes were shown to be flavoproteins consisting of subunits of 65 kDa. The A.
      nidulans enzyme was biochemically similar to POx reported in literature. From all
      substrates, the highest catalytic efficiency was found with D-glucose. In
      addition, the enzyme catalyzes the two-electron reduction of 1,4-benzoquinone,
      several substituted benzoquinones and 2,6-dichloroindophenol. As judged by the
      catalytic efficiencies (k (cat)/k(m)), some of these quinone electron acceptors
      are better substrates for pyranose oxidase than oxygen. The enzyme from A. oryzae
      was physically similar but showed lower kinetic constants compared to the enzyme
      from A. nidulans. Distinct differences in the stability of the two enzymes may be
      attributed to a deletion and an insertion in the sequence, respectively.

PMID- 21968653
TI  - Pasteurella multocida CMP-sialic acid synthetase and mutants of Neisseria
      meningitidis CMP-sialic acid synthetase with improved substrate promiscuity.
AB  - Cytidine 5'-monophosphate (CMP)-sialic acid synthetases (CSSs) catalyze the
      formation of CMP-sialic acid from CTP and sialic acid, a key step for
      sialyltransferase-catalyzed biosynthesis of sialic acid-containing
      oligosaccharides and glycoconjugates. More than 50 different sialic acid forms
      have been identified in nature. To facilitate the enzymatic synthesis of
      sialosides with diverse naturally occurring sialic acid forms and their non
      natural derivatives, CMP-sialic acid synthetases with promiscuous substrate
      specificity are needed. Herein we report the cloning, characterization, and
      substrate specificity studies of a new CSS from Pasteurella multocida strain P
      1059 (PmCSS) and a CSS from Haemophillus ducreyi (HdCSS). Based on protein
      sequence alignment and substrate specificity studies of these two CSSs and a
      Neisseria meningitidis CSS (NmCSS), as well as crystal structure modeling and
      analysis of NmCSS, NmCSS mutants (NmCSS_S81R and NmCSS_Q163A) with improved
      substrate promiscuity were generated. The strategy of combining substrate
      specificity studies of enzymes from different sources and protein crystal
      structure studies can be a general approach for designing enzyme mutants with
      improved activity and substrate promiscuity.

PMID- 21968654
TI  - An improved screening method for microorganisms able to convert crude glycerol to
      1,3-propanediol and to tolerate high product concentrations.
AB  - A new screening method was developed and established to find high-performance
      bacteria for the conversion of crude glycerol to 1,3-propanediol. Three soil
      samples from palm oil-rich habitats were investigated using crude glycerol of a
      German biodiesel plant. Nine promising 1,3-propanediol producers could be found.
      Because of a special pH buffer system, a fast evaluation on microscale and high
      1,3-propanediol concentrations up to 40 g L-1 could be achieved. Three strains
      demonstrated very high product tolerance and were identified as Clostridium
      butyricum. Two strains, AKR91b and AKR102a, grew and produced 1,3-propanediol in
      the presence of 60 g L-1 initial 1,3-propanediol, the strain AKR92a even in the
      presence of 77 g L-1 1,3-propanediol. The strains AKR91b and AKR102a tolerated up
      to 150 g L-1 crude glycerol and produced 80% of the 1,3-propanediol attained from
      pure glycerol of the same concentration. Further criteria for the choice of a
      production strain were the pathogenicity (risk class), ability to grow on low
      cost media, e.g., with less yeast extract, and robustness, e.g., process
      stability after several bioconversions. Overall, the strain C. butyricum AKR102a
      was chosen for further process optimization and scale-up due to its high
      productivity and high final concentration in a pH-regulated bioreactor.

PMID- 21968655
TI  - Comparison of separate hydrolysis and fermentation and simultaneous
      saccharification and fermentation processes for ethanol production from wheat
      straw by recombinant Escherichia coli strain FBR5.
AB  - Ethanol production by recombinant Escherichia coli strain FBR5 from dilute acid
      pretreated wheat straw (WS) by separate hydrolysis and fermentation (SHF) and
      simultaneous saccharification and fermentation (SSF) was studied. The yield of
      total sugars from dilute acid (0.5% H(2)SO(4)) pretreated (160  degrees C, 10
      min) and enzymatically saccharified (pH 5.0, 45  degrees C, 72 h) WS (86 g/l) was
      50.0 +/- 1.4 g/l. The hydrolyzate contained 1,184 +/- 19 mg furfural and 161 +/-
      1 mg hydroxymethyl furfural per liter. The recombinant E. coli FBR5 could not
      grow at all at pH controlled at 4.5 to 6.5 in the non-abated wheat straw
      hydrolyzate (WSH) at 35  degrees C. However, it produced 21.9 +/- 0.3 g ethanol
      from non-abated WSH (total sugars, 44.1 +/- 0.4 g/l) in 90 h including the lag
      time of 24 h at controlled pH 7.0 and 35  degrees C. The bioabatement of WS was
      performed by growing Coniochaeta ligniaria NRRL 30616 in the liquid portion of
      the pretreated WS aerobically at pH 6.5 and 30  degrees C for 15 h. The bacterium
      produced 21.6 +/- 0.5 g ethanol per liter in 40 h from the bioabated
      enzymatically saccharified WSH (total sugars, 44.1 +/- 0.4 g) at pH 6.0. It
      produced 24.9 +/- 0.3 g ethanol in 96 h and 26.7 +/- 0.0 g ethanol in 72 h per
      liter from bioabated WSH by batch SSF and fed-batch SSF, respectively. SSF
      offered a distinct advantage over SHF with respect to reducing total time
      required to produce ethanol from the bioabated WS. Also, fed-batch SSF performed
      better than the batch SSF with respect to shortening the time requirement and
      increase in ethanol yield.

PMID- 21968656
TI  - Sodium thiosulfonate salts: molecular and supramolecular structural features and
      solution radiolytic properties.
AB  - Three sodium thiosulfonate salts, NaMeS(2)O(2).H(2)O, NaPhS(2)O(2) and
      NaMeC(6)H(4)S(2)O(2) have been prepared by the direct reaction of the sodium
      sulfinate salts with elemental sulfur, a clean, benign route that produces no by
      products. The structures of the phenyl (which crystallised as a hydrate,
      NaPhS(2)O(2).1.5H(2)O) and p-tolyl compounds were determined by X-ray
      crystallography. For the p-tolyl derivative, NaMeC(6)H(4)S(2)O(2), the unexpected
      coordination of the pendant sulfur atom was found, a feature not reported
      previously for thiosulfonate salts, and observed only in two of the more common
      thiosulfate salts. Intermolecular CH/pi interactions are postulated to contribute
      to the driving force of sulfur coordination, otherwise a different orientation of
      the aromatic rings would be expected. For NaPhS(2)O(2).1.5H(2)O, the water
      ligands and thiosulfonate anions each contribute three oxygen atoms to form a
      NaO(6) coordination sphere. The thiosulfonate and water oxygens bridge to other
      sodium atoms forming a three-dimensional layer structure consisting of sheets of
      NaPhS(2)O(2).1.5H(2)O with a hydrophilic interior layer, comprising the sodium
      ions, water ligands and -S(2)O(2)(-) groups, and a hydrophobic exterior formed by
      the phenyl substituent. The structure is further stabilised by an extensive H
      bonding network between the ligated water and the non-coordinating thiosulfonate
      sulfur atom forming part of the hydrophilic layer and by weak intermolecular edge
      to-face CH/pi interactions between the sheets. Investigation of the radical
      chemistry of the three salts using pulse radiolysis indicated that oxidation of
      NaMeS(2)O(2).H(2)O involves formation of a sulfur-centred radical rather than
      hydrogen abstraction from the methyl substituent, whereas oxidation of the
      aromatic ring is the preferred pathway for the phenyl and p-tolyl derivatives.

PMID- 21968657
TI  - Enhanced phosphorylation of STAT-1 is dependent on double-stranded RNA-dependent
      protein kinase signaling in HLA-B27-expressing U937 monocytic cells.
AB  - OBJECTIVE: To study the phosphorylation of STAT-1 in HLA-B27-transfected human
      monocytic cells and the role of the signaling molecules double-stranded RNA
      dependent protein kinase (PKR) and p38 in STAT-1 phosphorylation. METHODS: U937
      human monocytic cell transfectants stably expressing wild-type HLA-B27 or mutated
      HLA-B27 heavy chains with amino acid substitutions in the B pocket were prepared.
      Mock-transfected cells were prepared using the antibiotic resistance vectors
      (pSV2neo or RSV5neo) alone. Phorbol myristate acetate-differentiated cells were
      stimulated with lipopolysaccharide (LPS) or infected with Salmonella enteritidis.
      The phosphorylation and expression levels of STAT-1 protein were detected by
      Western blotting and flow cytometry. Specific inhibitors were added in cell
      culture to study the role of PKR and p38 in STAT-1 phosphorylation. RESULTS: STAT
      1 was constitutively highly phosphorylated on the tyrosine 701 residue in HLA-B27
      positive monocytic cells when compared to control cells, even prior to
      stimulation with LPS or bacteria. This phenotype was associated with the
      expression of HLA-B27 heavy chains that misfold. In addition, phosphorylation of
      STAT-1 was dependent on PKR. CONCLUSION: Our results show that STAT-1 tyrosine
      701 is constitutively highly phosphorylated in the HLA-B27-expressing
      monocyte/macrophage cell line. Since phosphorylation of tyrosine 701 on STAT-1 is
      sufficient to induce interferon (IFN)-dependent genes, constitutive activity of
      this phosphorylation site may lead to the overexpression of IFN-dependent genes,
      as well as other STAT-1-dependent genes, in HLA-B27 monocyte/macrophages. Our
      results offer a mechanism by which B27 expression alone, without any external
      trigger, is potentially capable of inducing activation of STAT-1, a critical
      regulator of the inflammatory response.

PMID- 21968659
TI  - Clinical evidence for the activity of tetrahydroxypropyl ethylenediamine (THPE),
      a new anti-aging active cosmetic.
AB  - BACKGROUND/ OBJECTIVES: The cellular surface modification of superficial
      epidermal keratinocytes can induce immediate skin tensioning effects and may
      improve signs of skin aging. Tetrahydroxypropyl ethylenediamine (THPE) is an
      active that has been described to induce keratinocytes' morphological changes in
      vitro. We conducted an in vivo study to assess anti-aging clinical benefits of a
      THPE-containing product. METHODS: An eight-week double-blind, randomized intra
      individual placebo controlled clinical study was performed to evaluate the
      clinical benefits of a 2.5% THPE-containing cream. This study included 41
      Caucasian women who received the THPE cream product on one side of the face and a
      placebo cream on the other side daily. Evaluations were performed at baseline, 45
      minutes after first application, week 4 and week 8 and included clinical
      examination and digital photography. RESULTS: The study demonstrated the
      immediate lifting effect of a 2.5% THPE-containing cream. Forty-five minutes
      after a single application on the face, as the skin surface smoothed out, light
      reflection was modified: healthy glow and radiance of the skin were significantly
      improved (respectively 22.9% and 40% of improvement) and skin yellowishness was
      reduced (7.1%). Notably, the THPE-treated side was significantly lifted, both
      immediately after product application (8.1%) and after 8 weeks of application
      (14%), compared to the placebo-treated side. CONCLUSION: This clinical study
      demonstrated that the effect of a 2.5% THPE-containing cream on the keratinocytes
      cells leads to an immediate and long-term clinical improvement of the skin
      appearance (radiance and skin firmness, skin lifting) and can therefore be
      considered as a new anti-aging cosmetic active.

PMID- 21968658
TI  - Green tea extract protects human skin fibroblasts from reactive oxygen species
      induced necrosis.
AB  - Oxidative damage by reactive oxygen species (ROS) plays a major role in skin
      aging, carcinogenesis and inflammation. Little is known about the protective
      effects of green tea extract (GTE) on toxic ROS-induced skin death. We use an in
      vitro model of normal human skin fibroblasts (AG13145) to study the effects of
      green tea extract (GTE) on hydrogen peroxide (H(2)O(2)) induced necrosis. Cell
      morphology, numbers, apoptosis, necrosis, and ROS were assessed by
      epifluorescence microscopy and flow cytometry. This study demonstrates that GTE
      protected from H(2)O(2)-induced necrosis in a dose-dependent manner, with highest
      dose GTE (100 ng/mL) resulting in the most protection from necrosis, as assessed
      by improved cell morphology, increased cell numbers, and decreased necrosis. The
      protective effects of GTE on H(2)O(2)-induced necrosis appear to be mediated
      directly by decreasing intracellular ROS. The present study suggests that
      pretreatment with high doses of GTE could protect from toxic ROS-induced injury
      of skin in the clinical setting. However, additional studies are necessary to
      determine the clinical utility of GTE for decreasing skin cell ROS, necrosis and
      inflammation.

PMID- 21968660
TI  - A phase 2, double-blind, randomized, placebo-controlled trial of a novel
      nutritional supplement product to promote healthy skin.
AB  - BACKGROUND: Despite an abundance of nutritional supplements, very few well
      controlled trials have assessed their beneficial effect on the skin, such as
      hydration, antioxidant levels, texture or appearance. The objective of the
      following placebo-controlled, double-blind study was to determine the effects of
      the Skin Health Experimental Product (SHEP) on skin health. METHODS: The study
      enrolled healthy men and women aged 30 years or older. Subjects were randomized
      to receive a twice-daily regimen of SHEP or placebo. The effects SHEP had on
      overall skin appearance and health were assessed by measuring improvements in:
      (1) skin hydration using a closed-aperture transepidermal water-loss moisture
      meter and a vapometer; (2) skin texture using silicon profilometry; (3) skin
      carotenoid concentration using Raman spectrometry; and (4) reported self-image
      assessments using the Global Aesthetic Improvement Scale (GAIS). RESULTS: SHEP
      treated subjects demonstrated a significant reduction in fine lines compared to
      the placebo-treated group. Raman spectroscopy showed that SHEP increased
      carotenoids at some measurement sites. Based on the GAIS, SHEP-treated subjects
      were three times more likely to perceive an improvement in their appearance
      compared to placebo-treated subjects (P>0.049). CONCLUSION: The orally
      administered SHEP nutritional supplement improves skin texture, carotenoid levels
      in specific areas of the hand, and improves patients' perception of skin health.

PMID- 21968661
TI  - Evaluation of moisturizing effect of methanolic extract of five medicinal plants
      incorporated into cream bases using impedance and extensiometry methods.
AB  - BACKGROUND: Skin moisturizing is an important issue due to its impact on skin
      function. Adverse reactions to herbal extracts have been rarely reported and can
      be used in moisturizers. This study was conduct to evaluate moisturizing effect
      of a methanolic extract of five medicinal plants incorporated into cream bases.
      METHODS: Methanolic extract of five medicinal plants including olive, burdock,
      licorice, mallow and marsh horsetail was prepared. The extracts were dissolved in
      distilled water completely and freeze-dried to a dry powder. These extracts were
      added separately to the cream based formulation that has been suggested to be
      appropriate for adding herbal extracts. Moisturizing effects of these creams with
      herbal extracts were assessed using the impedance method on 12 rats equally
      divided into six groups (one control and five cases), as well as the
      extensiometry method on 25 mice divided into five groups (in each group one cream
      with herbal extract and control cream were tested concurrently). Obtained results
      were compared with the control cream based. RESULTS: The maximum moisturizing
      effect was observed with the marsh horsetail. Other creams with herbal extracts,
      except the one with the licorice, also exerted significantly higher moisturizing
      effect compared to the controls (P<0.05). Regarding the force for skin tearing,
      the differences were statistically significant in all groups when compared to the
      control group (P<0.05) and the highest difference was seen in the marsh horsetail
      group (2.0832 +/- 0.6811 kgN). CONCLUSIONS: The highest moisturizing activity was
      observed using marsh horsetail extract that can be explained by flavonoids
      content of marsh horsetail.

PMID- 21968662
TI  - Effect of retinoid pretreatment on outcomes of patients treated by photodynamic
      therapy for actinic keratosis of the hand and forearm.
AB  - BACKGROUND/OBJECTIVE: Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA)
      has been shown to be useful in both spot and field treatments of actinic
      keratoses (AK). This study evaluates the safety and efficacy of pretreatment of
      AK lesions on the dorsal hands and forearms with tazarotene gel (0.1%) twice a
      day for one week before broad-area ALA PDT. METHODS: Ten subjects aged 75.4 +/-
      11.6 years (mean plus minus SD) with at least four AK lesions on their dorsal
      forearm or hand were randomized so that one dorsal hand or forearm was pretreated
      with tazarotene gel (0.1%) twice daily for one week before ALA PDT with blue
      light. The other hand or forearm (control) was not pretreated. After seven days,
      ALA was applied to both sides and incubated 60 minutes before irradiation with
      blue light. ALA was applied first only to the AK lesions and then to the entire
      treatment area (defined as the extensor surface of the hand or forearm between
      the elbow and the base of the fingers) before 60-minute incubation. The ALA area
      on the control side was occluded during the 60-minute incubation. Efficacy and
      adverse effects were evaluated within 48 hours and eight weeks later. RESULTS:
      For both the pretreated and control group, lesion counts of the target areas
      decreased significantly from baseline to eight weeks after ALA PDT. Reduction
      percentages of the target area, however, did not differ significantly between the
      two groups. When reduction percentages of the entire treatment area for both
      groups were compared the difference between the two groups was of borderline
      significance (P=0.0547). When the entire treatment area was analyzed, lesion
      counts of the tazarotene group differed significantly from baseline at eight
      weeks (P=0.0002), but this was not the case with the control group (P=0.0365).
      Adverse events were limited to those expected after ALA PDT. Erythema was
      significantly more severe (P=0.0029) in the pretreated arm five minutes after ALA
      PDT. CONCLUSION: Pretreatment of AK lesions on the dorsal hand and forearm with
      tazarotene gel (0.1%) may enhance the therapeutic effect of ALA PDT without
      serious side effects.

PMID- 21968663
TI  - Treatment of interdigital tinea pedis: once-daily therapy with sertaconazole
      nitrate.
AB  - The treatment of cutaneous fungal infections has been shown to be directly
      affected by the extent of patients' adherence to therapy regimens that are often
      cumbersome and last for several weeks. One useful alternative approach is once
      daily dosing of topical antifungal agents rather than the traditional twice-daily
      regimen, an example of what has been called a "forgiving" regimen, designed to
      promote patient adherence. Sertaconazole, an imidazole antifungal agent, is known
      to be safe and effective when used twice daily in the treatment of tinea pedis.
      This report discusses a small (n=32) clinical trial designed to determine whether
      sertaconazole nitrate 2% cream, used once daily, is as effective as the
      traditional regimen. Results demonstrated that sertaconazole is as effective when
      used once daily for four weeks. Patients showed rapid improvement in pruritus as
      early as week 2, and at six weeks' follow up, all patients were free of erythema
      while 93.8 percent were free of pruritus; no relapses had occurred. These
      encouraging findings suggest that sertaconazole nitrate may be useful in a once
      daily regimen and also may result in better patient adherence to therapy.

PMID- 21968664
TI  - A double-blind, randomized, vehicle-controlled study evaluating the efficacy and
      safety of naftifine 2% cream in tinea cruris.
AB  - OBJECTIVE: Naftifine HCl 2% cream (NAFT-2%) is a topical allylamine antifungal
      preparation under development in the U.S. The objective of this randomized,
      double-blind, vehicle-controlled study was to evaluate the efficacy and safety of
      a two-week course of once-daily NAFT-2% vs. vehicle in the treatment of Tinea
      cruris ("jock itch"). METHODS: A total of 334 subjects with T. cruris were
      enrolled and randomly assigned to NAFT-2% (n=166) or vehicle (n=168), which was
      applied once daily for 14 days. Efficacy and safety were evaluated at week 2 (end
      of treatment) and week 4. Efficacy measures included complete cure, treatment
      effectiveness, mycological cure, clinical cure, and clinical success and were
      analyzed only in subjects with a positive potassium hydroxide (KOH) and
      dermatophyte culture at baseline (n=75, naftifine; n=71, vehicle). Safety was
      assessed by adverse events and changes from baseline in clinical status and
      laboratory studies. RESULTS: At week 4, 25 percent of naftifine-treated subjects
      achieved complete cure vs. three percent of vehicle subjects and 72 percent
      achieved mycological cure vs. 16 percent of vehicle treated subjects (one-sided,
      P<0.001). Treatment effectiveness was achieved in 60 percent of NAFT-2% subjects
      vs. 10 percent of vehicle subjects (one-sided, P<0.001). Clinical cure rate and
      clinical success rate were 33 percent and 84 percent in NAFT-2% subjects,
      respectively vs. 10 percent and 46 percent in vehicle subjects (both P is less
      than 0.001, 2-sided). Week 2 efficacy response rates in NAFT-2% subjects were all
      lower than at week 4 but were significantly higher than week 2 vehicle-treated
      counterparts (P<0.025). Treatment-related AE occurred in 11 subjects (7 NAFT-2%,
      4 vehicle) during the study. The most common AE in both groups were contact
      dermatitis (2 NAFT-2%), pruritus (2 vehicle), and application site reaction (1
      per group). CONCLUSION: NAFT-2% applied once daily for two weeks (one-half the
      treatment duration for naftifine 1% cream) is efficacious and safe for the
      treatment of T. cruris.

PMID- 21968665
TI  - Comparing the clinical attributes of abobotulinumtoxinA and onabotulinumtoxinA
      utilizing a novel contralateral Frontalis model and the Frontalis Activity
      Measurement Standard.
AB  - BACKGROUND: Studies on the pharmacodynamics of abobotulinumtoxinA (ABO) and
      onabotulinumtoxinA (ONA) have produced inconsistent results. This may be due to
      the lack of objective measurement methods. OBJECTIVE: To assess and compare
      pharmacodynamic attributes, including onset of action, spread and efficacy of ABO
      and ONA using a novel Frontalis Activity Measurement Standard (FMS) and 4-point
      Frontalis Rating Scale (FRS). METHODS: Twenty subjects with severe frontalis
      lines at maximum elevation received equal volumes of ABO or ONA using a dose
      ratio of 2.5:1 in five injection points on contralateral sides of the frontalis
      (statistical n=40). Subjects were evaluated using the FMS and FRS for 30 days
      using pre-defined endpoints for onset and effectiveness. Other assessments
      included areas of effectiveness and injection pain. RESULTS: For ABO vs. ONA, the
      FMS revealed a median Initial Onset of 12 vs. 48 hours (P is less than 0.001),
      Full Onset of 24 vs. 72 hours (P is less than 0.001) and Complete Onset of three
      vs. five days (P=0.01). The FRS indicated an Initial Onset for ABO and ONA of 18
      hours vs. two days (P=0.002), Full Onset of two vs. three days (P=0.001) and
      Complete Onset of four days vs. eight days (P=0.01). The FMS showed 90 percent of
      ABO treatment achieved Complete Efficacy vs. 75 percent for ONO, while 90 percent
      of ABO treatments reached Complete Efficacy using the FRS vs. 65 percent for ONO.
      No differences in area of effectiveness or spread were observed. Most subjects
      (80%) reported ABO injections were less painful than ONA injections (P< 0.05).
      CONCLUSION: The FMS appears to be a sensitive, objective tool for measuring ABO
      and ONA pharmacodynamics. Using a dose ratio of 2.5:1, ABO displayed
      significantly earlier onset of effect and less injection pain than ONA but
      similar areas of effectiveness.

PMID- 21968666
TI  - Cutaneous reactions to non-steroidal anti-inflammatory drugs.
AB  - We retrospectively reviewed the records of 195 patients with suspected cutaneous
      reactions from NSAIDs. Two hundred and six different non-steroidal anti
      inflammatory drugs (NSAIDs) were suspected of causing cutaneous reactions, and
      the most frequent suspected causative NSAID was ibuprofen (25.7%). Angioedema
      and/or urticaria were the most frequent cutaneous reactions (54.4%), and the
      foremost suspected causative drug for these reactions was ibuprofen. The second
      most frequently found cutaneous reaction was maculopapular eruption (26.2%), and
      celecoxib was the most commonly suspected causative NSAID for it. The primary
      suspected NSAIDs causing fixed drug eruption were in enolic acid group.
      Furthermore, drug hypersensitivity syndrome was diagnosed in five patients, and
      Stevens-Johnson syndrome and toxic epidermal necrolysis were detected in five
      patients.

PMID- 21968667
TI  - Oregano extract ointment for wound healing: a randomized, double-blind,
      petrolatum-controlled study evaluating efficacy.
AB  - BACKGROUND: Wound healing is a dynamic and complex process affected by tissue
      hydration, the presence of bacteria, inflammation, and other variables. Oregano
      has potent antibacterial, antifungal, antioxidant, and anti-inflammatory
      properties. Studies of oregano ointment on wound healing are lacking. OBJECTIVE:
      To determine the efficacy of 3% oregano extract ointment on wound healing.
      METHODS: An investigator initiated, randomized, double-blind, petrolatum
      controlled study was performed to determine the effects of oregano ointment on
      wound healing. Forty patients who underwent surgical excision were enrolled and
      randomized. Cultures were obtained on day 12 and scars were evaluated using the
      Patient and Observer Scar Assessment tool on day 12, 45, and 90. RESULTS: The
      oregano ointment group had 19 percent of cultures test positive for Staphlococcus
      aureus compared to 41 percent in the petrolatum group. One patient in the oregano
      ointment group developed a cellulitis compared to three patients in the
      petrolatum group. The oregano group had a statistically significant improvement
      over petrolatum in scar color, pigmentation, and pliability. CONCLUSION: Oregano
      extract ointment decreased bacterial contamination and subsequent infection on
      post-surgical wounds and had equivalent overall scar appearance compared to
      petrolatum.

PMID- 21968668
TI  - Cryosurgical treatment of warts: dimethyl ether and propane versus liquid
      nitrogen - case report and review of the literature.
AB  - For years, dermatologists have relied on cryotherapy with liquid nitrogen as a
      safe and effective treatment for warts. More recently, several over-the-counter
      (OTC) wart-freezing therapies have become available. Manufacturers have
      substituted liquid nitrogen with dimethyl ether and propane (DMEP), and marketed
      these new preparations to be safe and effective alternatives to in-office
      cryotherapy with liquid nitrogen. However, data from in vitro studies and
      comparative studies in humans refute manufacturers' claims that these products
      reproduce in-office cryotherapy.

PMID- 21968669
TI  - Efficacy of a novel rosacea treatment system: an investigator-blind, randomized,
      parallel-group study.
AB  - INTRODUCTION: A rosacea treatment system (cleanser, metronidazole 0.75% gel,
      hydrating complexion corrector, and sunscreen SPF30) has been developed to treat
      rosacea. METHODS: Thirty women with mild or moderate erythema of rosacea on their
      facial cheeks were randomly assigned to use one of the following for 28 days: the
      rosacea treatment system (RTS); RTS minus metronidazole (RTS-M); or metronidazole
      0.75% gel plus standard skin care (standard cleanser and standard
      moisturizer/sunscreen) (M+SSC). RESULTS: At day 28, global improvement was
      evident in 90 percent of patients using RTS, 60 percent using RTS-M, and 67
      percent using M+SSC. Erythema was significantly lower with RTS from day 14
      onward, and unchanged with M+SSC. The proportion of patients reporting their skin
      was easily irritated at least sometimes was 40 percent with RTS, 70 percent with
      RTS-M, and 89 percent with M+SSC. CONCLUSION: The rosacea treatment system may
      offer superior efficacy and tolerability to metronidazole plus the standard skin
      care used in this study.

PMID- 21968670
TI  - Clinical evaluation of safety and efficacy of a new topical treatment for
      onychomycosis.
AB  - OBJECTIVE: This clinical study assessed the safety and efficacy of an
      investigational topical product for the treatment of onychomycosis (nail fungus).
      METHOD: A prospective, multi-center, single-arm, self-controlled clinical
      investigation was done with adult subjects that met the inclusion criteria,
      primarily culture-confirmed dermatophyte infection of at least one great toe.
      Subjects self-treated in a weekly regimen of topical application for six months,
      with clinical assessment at one, three, and six months. Primary efficacy endpoint
      was clearance of fungal nail infection after six months of weekly treatment.
      Primary safety endpoint was freedom from product-related adverse events for the
      duration of the treatment term. RESULTS: Fifty males and 13 females, ages 24 to
      65, infected with Trichophyton (n=62) or Epidermophyton (n=1) were enrolled; 53
      completed six months of assessment. Sixty percent showed improvement in clinical
      parameters (nail color, nail plate involvement, onycholysis, thickness, and
      hyperkeratosis) at six months. Cumulative rates of dermatophyte-negative culture
      results (test of cure) were 28, 36, and 62 percent of subjects after one, three,
      and six months of treatment, respectively. Three minor adverse events were device
      related, with no unanticipated or serious adverse events. LIMITATIONS: This study
      was single-arm and self-controlled; 53 of 63 enrolled subjects completed the
      study. CONCLUSION: This study describes a new topical medical device with safety
      and efficacy profiles that compare favorably to results reported for topically
      applied onychomycosis drug treatments.

PMID- 21968671
TI  - CD70 and Th17 are involved in human contact sensitivity.
AB  - CD70 (CD27L) has been shown to be preferentially expressed on Th1, but not Th2,
      CD4+ lymphocytes in murine contact sensitivity. The CD70-CD27 co-stimulatory
      pathway as well as the Th17 subset of lymphocytes have also been identified in
      human contact sensitivity reactions. The authors have previously reported
      increased expression of CD70 and the Th17-specific transcription factor retinoid
      orphan receptor gamma T in the elicitation phase of allergic contact dermatitis
      by reverse transcriptase-polymerase chain reaction. The manipulation of these
      pathways has potential for ameliorating autoimmune and inflammatory disorders
      such as allergic contact dermatitis, psoriasis and rheumatoid arthritis. Also,
      upregulation of the CD70-CD27 and Th17 pathways has been associated with the
      remarkable ability of topical sensitizers to treat warts and skin cancers
      including melanoma. As natural killer and natural killer T cells are also
      involved in contact sensitivity, future studies investigating the function of
      these cells are necessary to elucidate the transition between innate and acquired
      immune responses in the context of the Th1/Th2/Th17 and regulatory T cell
      paradigm.

PMID- 21968672
TI  - Tattoo sites and psoriasis.
AB  - The Koebner phenomenon refers to the development of lesions in response to injury
      of previously uninvolved skin. It occurs in psoriasis and a number of other
      inflammatory diseases. We present a patient who developed a Koebner reaction at
      the site of a tattoo. Treatment with ustekinumab resulted in striking clearance
      of the psoriasis changes at the tattoo site.

PMID- 21968673
TI  - Metallic taste as a side effect of topical fluorouracil use.
AB  - Topical fluorouracil is widely used for the treatment of precancerous and
      cancerous lesions of the skin. The most common side effect of this medication is
      localized irritant dermatitis. The authors report a case of dysgeusia with
      metallic taste as a side effect of this medication. While not previously seen
      with topical use, this is not an uncommon side effect seen with systemic
      administration of 5-fluorouracil. The etiology of dysgeusia from chemotherapeutic
      agents and systemic absorption of fluorouracil is discussed.

PMID- 21968674
TI  - Levamisole induced necrosis of the skin and neutropenia following intranasal
      cocaine use: a newly recognized syndrome.
AB  - Levamisole is a veterinary anti-helminthic used to treat several autoimmune
      conditions but also commonly utilized as an additive in cocaine distribution.
      Toxicity resulting in agranulocytosis and cutaneous necrosis in association with
      cocaine use is an infrequently described phenomenon of an emerging problem.
      Although levamisole is found extensively in the cocaine supply of the United
      States, relatively few cases of necrotic skin lesions associated with intranasal
      use have been reported. The skin necrosis secondary to levamisole toxicity is
      characterized by variable findings on biopsy, ranging from leukocytoclastic
      vasculitis to occlusive vasculopathy. The following case describes a 54-year-old
      male who developed fever, agranulocytosis, p-ANCA autoantibodies and extensive
      skin necrosis following heavy intranasal cocaine use. Necrosis of greater than
      50% of the patient's total body surface area resulted and was followed by
      thorough wound debridement.

PMID- 21968675
TI  - Intralymphatic histiocytosis associated with orthopedic implants.

PMID- 21968676
TI  - Eruptive plexiform schwannomas in a child with neurofibromatosis I.

PMID- 21968677
TI  - Manifestations and treatment of cutaneous lupus erythematosus (part I of II).

PMID- 21968678
TI  - Gene expression analysis of demineralized bone matrix-induced osteogenesis in
      human periosteal cells using cDNA array technology.
AB  - Demineralized  bone matrix (DBM) has been widely investigated as a biomaterial to
      promote new  bone formation and is utilized clinically for bone repair and
      regeneration. We  investigated gene expression patterns of osteogenic
      differentiation in human  periosteal (HPO) cells cultured with demineralized bone
      matrix, using cDNA  array technology. Osteogenic differentiation of HPO cells was
      determined using  alkaline phosphatase assay. In order to examine differential
      gene expression  during osteogenic differentiation, total RNA was isolated from
      HPO cells in the  absence or presence of DBM on day seven and analyzed using
      osteogenesis cDNA  gene array. The selected genes were verified using reverse
      transcriptase  (RT)-PCR analysis. Human periosteal cells differentiated along an
      osteogenic  lineage after treatment of DBM. The alkaline phosphatase activity
      assay showed  that HPO cells differentiated into an osteogenic lineage. Gene
      expression of  HPO cells treated with DBM for seven days was analyzed with cDNA
      array and  RT-PCR analyses. Expression of biglycan, TGF-beta1, and TGF-betaR1 was
      upregulated, whereas collagen14A1  expression was downregulated, as confirmed by
      RT-PCR. Human periosteal cells expressed  osteogenesis genes when treated with
      DBM. These findings provide new insight  into the capability of demineralized
      bone matrix to modulate the osteogenic  differentiation of human periosteal
      cells.

PMID- 21968679
TI  - A transient assay for recombination demonstrates that Arabidopsis SNM1 and XRCC3
      enhance non-homologous recombination.
AB  - Replacement  of endogenous genes by homologous recombination is rare in plants;
      the majority  of genetic modifications are the result of transforming DNA
      molecules  undergoing random genomic insertion by way of non-homologous
      recombination.  Factors that affect chromatin remodeling and DNA repair are
      thought to have the  potential to enhance the frequency of homologous
      recombination in plants.  Conventional tools to study the frequencies of genetic
      recombination often rely  on stable transformation-based approaches, with these
      systems being rarely capable  of high-throughput or combinatorial analysis. We
      developed a series of vectors  that use chemiluminescent (LUC and REN) reporter
      genes to assay  the relative frequency of homologous and non-homologous
      recombination in  plants. These transient assay vectors were used to screen 14
      candidate genes  for their effects on recombination frequencies in Nicotiana
      benthamiana plants.  Over-expression of Arabidopsis genes with sequence
      similarity to SNM1 from yeast and XRCC3 from humans enhanced the frequency of 
      non-homologous recombination when assayed using two different donor vectors. 
      Transient N. benthamiana leaf systems were also used in an alternative  assay for
      preliminary measurements of homologous recombination frequencies,  which were
      found to be enhanced by over-expression of RAD52, MIM and RAD51 from yeast, as
      well as CHR24 from Arabidopsis. The  findings for the assays described here are
      in line with previous studies that  analyzed recombination frequencies using
      stable transformation. The assays we  report have revealed functions in non
      homologous recombination for the Arabidopsis  SNM1 and XRCC3 genes, so the
      suppression of these genes' expression  offers a potential means to enhance the
      gene targeting frequency in plants.  Furthermore, our findings also indicate that
      plant gene targeting frequencies  could be enhanced by over-expression of RAD52,
      MIM, CHR24,  and RAD51 genes.

PMID- 21968680
TI  - Inheritance of kernel row number, a multicategorical threshold trait of maize
      ears.
AB  - Information  about the inheritance of threshold traits is scarce, especially in
      plants. We  examined the genetic control of kernel row number in maize (Zea
      mays).  Knowledge of this inheritance is especially important because it is a
      primary  component of grain yield. This trait has a discontinuous distribution. 
      Characters like these are conceptualized as threshold traits. Crosses were made 
      between the inbred line Geneze 3 (G3) with many kernel rows and the inbreds 
      Argentino IV (A4) and Dente de Cravo (DC), with fewer kernel rows. The F(1) and
      F(2) generations  and the backcrosses BC(11) and BC(21) were  obtained for the
      combinations G3 x A4 and G3 x DC. These populations were  evaluated under field
      conditions, and the kernel row number was determined by  direct counting of
      approximately 14, 140 and 75 ears for the F(1), F(2) and  backcrosses,
      respectively. Genetic control was determined through estimates of  generation
      means and variance analysis and was also performed by Wright's  method for
      threshold traits. It was found that genetic control is predominantly  due to
      additive alleles. The component a, was greater than zero,  additive variance was
      positive and the variance of dominance did not differ  from zero. In the F(2)
      generation, the  range of the kernel row number was 10 to 28 in G3 x A4, while in
      G3 x DC it was  12 to 26. Inheritance of the number of kernel rows, estimated by
      the two  methods, gave similar results. This correspondence is due to adjusting
      of the  data to the normal distribution.

PMID- 21968681
TI  - Association between IGF2 and CYP21  gene polymorphisms and characteristics of
      economic interest in Nellore cattle.
AB  - We  analyzed two single nucleotide polymorphisms (SNPs) of the IGF2 and CYP21
      genes in Nellore cattle participating in the Brazilian Animal Breeding  Program.
      The SNPs were found in exon 6 of the IGF2 (insulin-like growth  factor 2) gene
      (RFLP/MboII) as well as in the promoter region of the CYP21 (steroid 21
      hydroxylase) gene (RFLP/HpaII) of these animals. The TC  heterozygotes were
      significantly more frequent than CC and TT homozygotes in  the RFLP/MboII
      polymorphism. The T allele was significantly more  frequent than the C allele in
      RFLP/HpaII polymorphism. This population  was found to be in Hardy-Weinberg
      equilibrium for these SNPs. Association of  these polymorphisms with expected
      progeny differences of reproductive and  productive traits was investigated, but
      proved to be significant only for DP550  (expected progeny differenced for weight
      at 365 days - IGF2 - RFLP/MboII)  and DP450 (expected progeny differenced for
      weight at 450 days - CYP21 -  RFLP/HpaII). This is the first study on the
      occurrence of these two  polymorphisms in this Zebu breed of cattle. A total of
      147 Nellore animals participating  in the Breeding Program of the Nellore Breed
      (PMGRN) under the management of  the National Association of Breeders and
      Researchers (ANCP) in the city of  Ribeirao Preto were analyzed.

PMID- 21968682
TI  - Molecular characterization of microduplication 22q11.2 in a girl with hypernasal
      speech.
AB  - We present a 12-year-old girl with karyotype 46,XX. A  comparative genomic
      hybridization array revealed a 3.172-Mb microduplication on  22q11.2. This
      chromosome 22q11.2 region microduplication has been described in  patients with
      variable phenotypes; a large majority of them have identical 3-Mb  duplications.
      The girl presented mild mental motor retardation, facial dysmorphism  consisting
      of a long narrow face, widely spaced eyes, downslanting palpebral  fissures,
      broad nasal base, short philtrum, thin upper lip, micro/retrognathia,  low set
      and retroverted ears, microcephaly, high-arched palate, hypoplastic  teeth, and
      hypernasal speech. She had delayed psychomotor development and  behavioral
      problems. Molecular characterization of patients differs greatly  among reports
      and detailed molecular characterization and documentation are  needed to better
      understand the effects of these duplications. This description  of the phenotype
      of a patient with microduplication on 22q11.2 will contribute to  the growing
      knowledge regarding deletions and duplications of the 22q11.2  region; this is
      important to conclude whether 22q11.2 duplication is a  microduplication syndrome
      or not.

PMID- 21968683
TI  - MtDNA variability in whitefly  (Bemisia tabaci) populations in Brazil.
AB  - Bemisia  tabaci (Hemiptera: Aleyrodidae) consists of a complex of 
      morphologically indistinct biotypes that vary mainly in their capacity to 
      transmit plant viruses and to induce physiological disorders in plants of 
      economic importance. The adaptability of B. tabaci to many regions of  the world
      has fostered the appearance of various biotypes and has resulted in a  broad
      spectrum of host plants. Our goal was to identify which biotypes were  present in
      four B. tabaci populations in Brazil. We quantified genetic  variability between
      and within populations. Three individuals were collected  from three host plant
      species: two populations on soybean (Campinas and  Rondonopolis), one on pumpkin
      (Barreiras) and one on tomato (Cruz das Almas) in  three States of Brazil (Sao
      Paulo, Mato Grosso, and Bahia). We chose one  sequence of the B biotype, obtained
      from GenBank; the Campinas population,  which had been previously characterized
      as biotype B, was used as a control for  this biotype. We also included one
      sequence of the Q biotype, obtained from  GenBank, as an outgroup. The COI region
      of the mtDNA gene was partially  amplified with the CI-J-2195 and L2-N-3014 pair
      of primers, and the reaction  products were sequenced. Based on distance-based
      algorithm analyses, we found  that all haplotypes belong to biotype B, which was
      confirmed by the haplotype  network. Genetic structure analyses showed that the
      host plant species does not  influence population structuring of this pest; only
      the geographic location  mattered.

PMID- 21968684
TI  - Expression of aquaporin-4 in  human supratentorial meningiomas with peritumoral
      brain edema and correlation of VEGF with edema formation.
AB  - Peritumoral  brain edema is a common complication of meningiomas. It is believed
      that  vascular endothelial growth factor (VEGF), as an angiogenic factor, plays a
      vital role in edema formation. Aquaporin-4 (AQP4) is a small integral membrane 
      protein that regulates water in the normal brain. However, the expression of 
      AQP4 and its relationship to VEGF in edematous meningiomas are not well known. 
      We studied tumor specimens of 59 human supratentorial meningiomas. Western blot 
      analysis was used to detect the expression of AQP4, and double-labeling 
      immunofluorescence histochemical staining was performed to determine the 
      relationship between AQP4 and VEGF. The AQP4 expression was significantly  higher
      in the edema group, in which the protein level was correlated with the  extent of
      edema. Greater VEGF expression was also observed in the edema group,  and a
      relationship between AQP4 and VEGF was found. We conclude that AQP4 is  involved
      in peritumoral brain edema formation in meningiomas and is also  closely related
      to the expression of VEGF.

PMID- 21968685
TI  - Bronchoscopically obtained volatile biomarkers in lung cancer.
AB  - BACKGROUND: The exhaled breath of lung cancer patients contains volatile organic
      compounds (VOCs) that differ from those in healthy individuals. These VOCs can be
      detected with methods such as ion mobility spectrometry (IMS); their origin
      remains unknown. METHODS: In 19 patients with lung cancer, exhaled breath was
      aspirated via the working channel of a flexible bronchoscope from both the tumor
      bearing and the opposite lung and analyzed with IMS. RESULTS: IMS measurement
      through the working channel of a bronchoscope was feasible and safe. In
      comparison to the opposite lung, we found two peaks that were significantly
      higher and three peaks that were significantly lower on the IMS of the tumor
      bearing site. VOCs differ in concentration depending on the histologic subtype.
      CONCLUSION: Our results indicate that VOCs in lung cancer patients are produced
      locally in or around the tumor, and it is most likely that these VOCs represent
      underlying metabolic processes of the tumor.

PMID- 21968686
TI  - Prevention of ER-negative breast cancer:  where do we stand?
AB  - Oestrogen receptor-negative and triple-negative breast cancers are types of
      aggressive tumours that account for approximately 30 and 15% of total breast
      cancers, respectively. Selective oestrogen receptor modulators and aromatase
      inhibitors are unable to treat and prevent these subtypes of mammary tumours.
      Thus, it is worth identifying new pathways, biomarkers, and agents that are
      effective in the treatment and prevention of these subtypes. Several classes of
      drugs have been studied, and many are still currently under investigation. We
      have attempted to conduct a state-of-the-art study on this important issue.

PMID- 21968687
TI  - Time trends in incidence, causes of death, and survival of cancer of unknown
      primary in Sweden.
AB  - Time trends in incidence, causes of death, and prognosis of cancer of unknown
      primary (CUP) could provide important clues for occult primary sites and thus
      result in effective organ-specific treatment, although such studies are seldom
      reported. We aimed at examining time trends in percentage and incidence rates,
      causes of death, and survival of CUP. A total of 50 545 patients with CUP were
      identified in the Swedish Cancer Registry from 1960 to 2008. We used direct
      standardization to standardize age-adjusted incidence rate to the Segi world
      population. Consistent increase before the late 1990s and dramatic decrease
      afterward was observed for both percentage and incidence of CUP in Swedes
      regardless of sex. Comparable time trends were noted in Norwegian and Finnish
      populations, but with several years earlier peaking times. For most anatomic
      sites, CUP and lung cancer were the two most common causes of death for patients
      with CUP irrespective of nodal involvement. Survival probability at 12 months
      after CUP was approximately 20% and then leveled off at approximately 10%.
      Adenocarcinoma accounted for most of this incidence variation and experienced the
      worst prognosis. High incidence rates and comparable time trends for CUP were
      observed in Sweden, Norway, and Finland. The increasing time trends may partially
      reflect the change of autopsy rates in these countries. The decreased incidence
      in the last decade could be due to an increasing identification of unknown
      primary caused by improving diagnostic methods. Histological types were
      significantly associated with survival in patients with CUP.

PMID- 21968688
TI  - Berberine prevents 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch
      carcinogenesis:  a biochemical approach.
AB  - Chemoprevention, a novel and useful approach in experimental oncology, deals with
      the prevention, suppression, or inhibition of carcinogenesis using natural or
      synthetic entities. This study evaluated the chemopreventive potential of
      berberine on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch
      carcinogenesis. Oral squamous cell carcinoma was developed in the buccal pouch of
      golden Syrian hamsters by painting with 0.5% DMBA in liquid paraffin three times
      a week for 14 weeks. Tumor incidence, tumor volume, tumor burden, phase I and
      phase II carcinogen detoxification agents, lipid peroxidation, antioxidant
      status, and histopathological changes were assessed in hamsters treated with DMBA
      alone and in DMBA+berberine-treated animals. Hundred percent tumor incidences
      with an imbalance in carcinogen-metabolizing enzymes and cellular redox status
      were observed in hamsters treated with DMBA alone. Oral administration of
      berberine at a dose of 75 mg/kg body weight (bw) to DMBA-treated hamsters
      completely prevented tumor incidence and restored the status of the above
      mentioned biochemical markers. Berberine, a traditional drug from Southeast Asia,
      shows promising chemopreventive efficacy in hamster buccal pouch carcinogenesis.

PMID- 21968689
TI  - Anticarcinogenic activity of nanoencapsulated quercetin in combating
      diethylnitrosamine-induced hepatocarcinoma in rats.
AB  - Hepatocellular carcinoma is the most common primary hepatic malignancy worldwide.
      N-Nitroso compounds act as strong carcinogens in various animals, including
      primates. Diethylnitrosamine (DEN) is a well known carcinogenic substance, which
      induces hepatic carcinoma. The theme of the study was to evaluate the therapeutic
      efficacy of nanoencapsulated flavonoidal quercetin (3,5,7,3',4'-pentahydroxy
      flavone, QC) in combating DEN-induced hepatocarcinogenesis in rats. DEN induced a
      substantial increase in relative liver weights with proliferation and development
      of hyperplastic nodules. A significant increase in hepatocellular and
      nephrotoxicity indicated by serum alkaline phosphatase, aspartate transaminase,
      alanine transaminase, urea, and creatinine was observed in DEN-treated animals.
      Maximum protection from such toxicity was provided by nanoparticulated QC.
      Elevated levels of conjugated diene in DEN-treated rats were lowered
      significantly by nanoparticulated QC. Antioxidant levels in hepatic cells were
      reduced significantly by the induction of DEN. Nanoparticulated QC was found most
      potent for complete prevention of DEN-induced reduction in antioxidant levels in
      the liver. Upregulation of glutathione-S-transferase activity by DEN induction
      was reduced maximally by nanoencapsulated QC. Nanoencapsulated QC completely
      protected the mitochondrial membrane of the liver from carcinoma mediated by DEN
      injection. A significant correlation could be drawn between DEN-induced tissue
      reactive oxygen species generation and cytochrome C expression in the liver.
      Nanoencapsulated QC completely prevented the DEN-induced cytochrome C expression
      in the liver significantly.

PMID- 21968690
TI  - Restriction of human papillomavirus DNA testing in primary cervical screening to
      women above age 30:  systematic review.
AB  - Cervical screening with human papillomavirus (HPV) testing is less specific for
      high-grade cervical intraepithelial neoplasia (>=CIN3) than cytology. The aim of
      this systematic review was to determine whether a restriction of HPV testing to
      women aged at least 30 years would eliminate the problem. On the basis of the
      data from randomized controlled trials, we calculated the relative detection of
      CIN1 and CIN2, and the relative risks of false-positive tests (positive tests
      without subsequent >=CIN3) per age group and trial for HPV testing versus
      cytology. For women aged at least 30 years in trials with a low cytology
      abnormality rate, detection of CIN1 increased significantly by 50-90% in the two
      trials with reported data; detection of CIN2 was doubled in three trials; the
      risks of false-positive HPV tests were also doubled. In trials with a high
      cytology abnormality rate, these risks were similar for HPV testing and cytology.
      Adverse effects of HPV testing were for both types of cytology settings,
      generally higher for women below than above the age of 30. Adverse effects were
      less common among women aged at least 30 years than among younger women. However,
      in older women HPV testing still led to more CIN1/CIN2 diagnoses and false
      positive tests than cytology.

PMID- 21968691
TI  - Catch me if you can: do the five-factor model personality traits moderate dropout
      and acute treatment response in post-traumatic stress disorder patients?

PMID- 21968692
TI  - Serum levels of IL-33 is increased in patients with ankylosing spondylitis.
AB  - Interleukin-33 (IL-33) is implicated in rheumatoid arthritis with effects of
      promoting tumor necrosis factor-alpha (TNF-alpha) and interleukin-17 (IL-17)
      productions, which have been demonstrated to play a pivotal role in ankylosing
      spondylitis (AS). However, changes of IL-33 levels and its effects in AS have not
      been investigated. Eighty-nine and 178 healthy controls were included in the
      current study. Erythrocyte sedimentation rate, serum levels of C-reactive
      protein, IL-17, and IL-33 were determined. Effects of IL-33 on TNF-alpha and IL-6
      productions were investigated. Effects of IL-33 on neutrophil migration were also
      evaluated. Serum levels of IL-33 were elevated in AS patients. Moreover, IL-33
      was significantly higher in active AS patients according to Bath Ankylosing
      Spondylitis Disease Activity Index. IL-33 concentrations in serum were positively
      correlated with TNF-alpha and IL-17 levels (IL-33 and TNF-alpha, r = 0.54, P <
      0.01; IL-33 and IL-17, r = 0.47, P < 0.01). IL-33 dose-dependently enhanced TNF
      alpha and IL-6 productions by peripheral blood mononuclear cells (PBMCs)
      responding to lipopolysaccharide. IL-33 induced neutrophil migration only in
      higher doses (>=10 ng/ml). Serum levels of IL-33 were elevated in AS patients. IL
      33 may play a role in AS development via enhancing TNF-alpha production by PBMCs
      and inducing neutrophil migration.

PMID- 21968693
TI  - Expression of human tumor necrosis factor-like weak inducer of apoptosis in
      patients with systemic lupus erythematosus.
AB  - The aim of this study was to compare the mRNA and serum expression of tumor
      necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) in patients with
      systemic lupus erythematosus (SLE) and healthy controls. Sixty-two SLE patients
      and 15 healthy controls were recruited in the study. TWEAK messenger RNA (mRNA)
      expression in peripheral blood mononuclear cells (PBMCs) from 33 of 62 patients
      was detected by relative quantification RT-PCR. TWEAK concentrations in the sera
      of all 62 patients were measured by ELISA. TWEAK mRNA expressions in PBMCs were
      decreased in SLE patients compared with healthy controls. Lower TWEAK mRNA
      expression was also found in the active SLE patients when compared to inactive
      ones. However, there was no significant difference between patients with lupus
      nephritis (LN) and those without. The level of serum TWEAK (sTWEAK) in SLE
      patients was increased when compared to healthy controls. In addition, the sTWEAK
      level was higher in SLE patients with vasculitis than those without vasculitis,
      and so was in comparison between patients with and without headache.
      Nevertheless, no significant differences were found between active SLE patients
      and inactive patients, or between LN patients and non-LN SLE patients. In this
      study, patients with SLE express low levels of TWEAK mRNA but high levels of
      sTWEAK. Additionally, sTWEAK level was associated with several clinical
      manifestations of SLE, indicating that TWEAK may play a complex role in SLE.

PMID- 21968694
TI  - Expanded role for interleukin-17 in rheumatoid arthritis.

PMID- 21968695
TI  - Representations of health and illness by Eastern European, South American and
      Italian care workers: a qualitative study.
AB  - This qualitative research examined the representations of health and illness
      presented by 30 individuals who work as care workers, from three different
      locations: Eastern Europe, South America and Italy. We led three focus groups for
      people who came from the same geographical area (intra-ethnic) and two for those
      from 'mixed' areas (inter-ethnic). From our content analyses, certain
      similarities and differences between the conceptualizations of health and illness
      emerged: in the intra-ethnic focus groups, Eastern Europeans focused on 'inner
      strengths', South Americans on 'love' and Italians on 'personal autonomy'. These
      peculiar traits were levelled in the inter-ethnic focus groups.

PMID- 21968697
TI  - Linking religion and spirituality with psychological well-being: examining self
      actualisation, meaning in life, and personal growth initiative.
AB  - Research largely shows that religion and spirituality have a positive correlation
      to psychological well-being. However, there has been a great deal of confusion
      and debate over their operational definitions. This study attempted to delineate
      the two constructs and categorise participants into different groups based on
      measured levels of religious involvement and spirituality. The groups were then
      scored against specific measures of well-being. A total of 205 participants from
      a wide range of religious affiliations and faith groups were recruited from
      various religious institutions and spiritual meetings. They were assigned to one
      of four groups with the following characteristics: (1) a high level of religious
      involvement and spirituality, (2) a low level of religious involvement with a
      high level of spirituality, (3) a high level of religious involvement with a low
      level of spirituality, and (4) a low level of religious involvement and
      spirituality. Multiple comparisons were made between the groups on three measures
      of psychological well-being: levels of self-actualisation, meaning in life, and
      personal growth initiative. As predicted, it was discovered that, aside from a
      few exceptions, groups (1) and (2) obtained higher scores on all three measures.
      As such, these results confirm the importance of spirituality on psychological
      well-being, regardless of whether it is experienced through religious
      participation. 

PMID- 21968696
TI  - The role of triglycerides in atherosclerosis.
AB  - Hypertriglyceridemia is a prevalent risk factor for cardiovascular disease (CVD)
      and increasingly important in the setting of current obesity and insulin
      resistance epidemics. High triglyceride (TG) levels are markers for several types
      of atherogenic lipoproteins. Patients who have hypertriglyceridemia may be at
      significant risk for CVD even if low-density lipoprotein cholesterol levels are
      at goal, and therefore warrant treatment that optimizes diet, reduces overweight,
      and promotes regular exercise. High-risk patients with hypertriglyceridemia, such
      as those with diabetes, CVD, or metabolic syndrome, may benefit from additional
      drug treatment aside from a statin to address other lipid abnormalities. In this
      discussion, we review the role of hypertriglyceridemia and its associated
      atherogenic lipoproteins in the pathogenesis of atherosclerosis, the relevance of
      a high TG level as a predictor of CVD, the cardiovascular outcomes from TG
      lowering intervention trials, and the current guidelines for treating
      hypertriglyceridemia.

PMID- 21968698
TI  - Solid renal masses: effectiveness and safety of image-guided percutaneous
      radiofrequency ablation.
AB  - With increasing emphasis on minimally invasive nephron-sparing techniques for
      treatment of renal tumors, image-guided percutaneous radiofrequency ablation
      (RFA) has emerged as a safe and effective method of tumor eradication that may be
      performed on an outpatient basis, with relatively low morbidity and mortality.
      This review addresses the clinical and technical considerations, risks,
      complications, and currently reported efficacy data pertaining to RFA of renal
      tumors, as well as the standardized approach to treatment and follow-up currently
      used in our practice.

PMID- 21968699
TI  - Failures in interpersonal psychotherapy (IPT): factors related to treatment
      resistances.
AB  - Interpersonal psychotherapy (IPT) is an effective treatment for depression across
      the lifespan and across cultures. However, even when delivered with fidelity,
      some patients drop out and others do not improve sufficiently. Attention to IPT
      treatment attrition, dropout, nonresponse, or failure can elucidate its
      limitations and the opportunities to improve its effectiveness. Studies of
      factors known to moderate and negatively predict IPT depression treatment
      response are reviewed along with recommended modifications to improve outcomes.
      Although the risk of treatment failure always exists, it is possible to enhance
      treatment effectiveness by attending to the therapeutic alliance, strategically
      addressing depression, and adapting IPT to patient characteristics. These include
      adding pharmacotherapy, extending the course of treatment, and targeting specific
      symptoms or interpersonal vulnerabilities. Case examples illustrate several of
      these points.

PMID- 21968700
TI  - RNA-cleaving properties of human apurinic/apyrimidinic endonuclease 1 (APE1).
AB  - We have recently identified apurinic/apyrimidinic endonuclease 1 (APE1) as an
      endoribonuclease that cleaves c-myc mRNA in vitro and regulates c-myc mRNA levels
      and half-life in cells. This study was undertaken to further unravel the RNA
      cleaving properties of APE1. Here, we show that APE1 cleaves RNA in the absence
      of divalent metal ions and, at 2 mM, Zn(2+), Ni(2+), Cu(2+), or Co(2+) inhibited
      the endoribonuclease activity of APE1. APE1 is able to cleave CD44 mRNA,
      microRNAs (miR-21, miR-10b), and three RNA components of SARS-corona virus
      (orf1b, orf3, spike) suggesting that, when challenged, it can cleave any RNAs in
      vitro. APE1 does not cleave strong doublestranded regions of RNA and it has a
      strong preference for 3' of pyrimidine, especially towards UA, CA, and UG sites
      at single-stranded or weakly paired regions. It also cleaves RNA weakly at UC,
      CU, AC, and AU sites in single-stranded or weakly paired regions. Finally, we
      found that APE1 can reduce the ability of the Dicer enzyme to process premiRNAs
      in vitro. Overall, this study has revealed some previously unknown biochemical
      properties of APE1 which has implications for its role in vivo.

PMID- 21968701
TI  - Interferon regulatory factor 5 activation in monocytes of systemic lupus
      erythematosus patients is triggered by circulating autoantigens independent of
      type I interferons.
AB  - OBJECTIVE: Genetic variants of interferon regulatory factor 5 (IRF-5) are
      associated with susceptibility to systemic lupus erythematosus (SLE). IRF-5
      regulates the expression of proinflammatory cytokines and type I interferons
      (IFNs) believed to be involved in the pathogenesis of SLE. The aim of this study
      was to determine the activation status of IRF-5 by assessing its nuclear
      localization in the immune cells of SLE patients and healthy donors, and to
      identify SLE-associated triggers of IRF-5 activation. METHODS: IRF-5 nuclear
      localization in subpopulations of peripheral blood mononuclear cells from 14
      genotyped SLE patients and 11 healthy controls was assessed using imaging flow
      cytometry. The activation and function of IRF-5 were examined after ex vivo
      stimulation of healthy donor monocytes with SLE serum or components of SLE serum.
      Cellular localization was determined by ImageStream flow cytometry, and cytokine
      expression was analyzed by quantitative polymerase chain reaction and enzyme
      linked immunosorbent assay. RESULTS: IRF-5 was activated in a cell type-specific
      manner; monocytes from SLE patients had constitutively elevated levels of nuclear
      IRF-5, as compared to natural killer cells and T cells. SLE serum was identified
      as a trigger for IRF-5 nuclear accumulation; however, neither IFNalpha nor SLE
      immune complexes could induce nuclear localization. Instead, autoantigens
      composed of apoptotic/necrotic material triggered IRF-5 nuclear accumulation in
      monocytes. Production of the cytokines IFNalpha, tumor necrosis factor alpha, and
      interleukin-6 in monocytes stimulated with SLE serum or autoantigens was
      distinct, yet showed a correlation with the kinetics of IRF-5 nuclear
      localization. CONCLUSION: This study provides the first formal proof that IRF-5
      activation is altered in the monocytes of SLE patients, which can be attributed,
      in part, to the SLE blood environment.

PMID- 21968703
TI  - Ferromagnetic heterotrinuclear Cu-Ni complexes of a compartmental chiral Schiff
      base.
AB  - Nickel(II) and copper(II) acetate react with the trinucleating compartmental
      Schiff base H(4)L (H(4)L = 6,6'-(E)-3,3'-(ethane-1,2-diyl)bis(1-(2-((E)-3-bromo-5
      chloro-2-hydroxybenzylideneamino)ethyl)imidazolidine-3,2-diyl)bis(2-bromo-4
      chlorophenol)) to produce the heterotrinuclear complexes
      [Ni(2)CuL(OAc)(2)].0.25H(2)O.2.5MeOH (1.0.25H(2)O.2.5MeOH) and
      [NiCu(2)L(OAc)(2)].3.25H(2)O.0.5MeOH (2.3.25H(2)O.0.5MeOH) as a function of the
      Ni(OAc)(2) : Cu(OAc)(2) molar ratio. The crystal structures of H(4)L,
      1.0.25H(2)O.2.5MeOH and 2.3.25H(2)O.0.5MeOH could be solved. The free ligand
      presents two stereogenic methine groups on the imidazolidine heterocycles. X-Ray
      diffraction studies on H(4)L determined that the solved crystal structure
      corresponds to a racemate formed by the (2R,2'R) and (2S,2'S) enantiomers,
      without detecting the (2R,2'S) diastereoisomer. The crystal structures of both
      heterotrinuclear complexes reveal that Ni(II) has a preference for the central
      ligand pocket, showing that this cavity discriminates between Ni(II) and Cu(II)
      when both species are present in the reaction medium. These results are validated
      by DFT calculations. As a consequence of the coordination, 1.0.25H(2)O.2.5MeOH
      and 2.3.25H(2)O.0.5MeOH are also chiral, but crystallise as racemates. In
      addition to their asymmetric methine groups, these complexes present four other
      stereogenic centres: the four coordinated imidazolidine N atoms. The luminescent
      properties of the ligand and both complexes were analysed, showing that the
      presence of the metals partially inhibits the emission of the ligand and
      apparently tunes the position of the secondary fluorescence emission band. The
      magnetic characterisation of 1.0.25H(2)O.2.5MeOH and 2.3.25H(2)O.0.5MeOH was also
      performed, showing the ferromagnetic behaviour of both complexes.

PMID- 21968702
TI  - PARP-1 and PARP-2: New players in tumour development.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) and PARP-2 belong to a family of enzymes
      that, using NAD(+) as a substrate, catalyze poly(ADP-ribosyl)ation of proteins.
      PARP-1 and PARP-2 catalytic activity is stimulated by DNA-strand breaks targeting
      mainly proteins involved in chromatin structure and DNA metabolism, providing
      strong support for a dual role of both PARP-1 and PARP-2 in the DNA damage
      response as DNA damage sensors and signal transducers to downstream effectors.
      The DNA damage response has important consequences for genomic stability and
      tumour development. In order to manipulate DNA damage responses to selectively
      induce tumour cell death, a considerable effort is centred on defining the
      molecular mechanisms that allow cells to detect, respond to, and repair DNA
      damage. PARP inhibitors that compete with NAD+ at the highly conserved enzyme
      active site are arisen as new potential therapeutic strategies as chemo- and
      radiopotentiation and for the treatment of cancers with specific DNA repair
      defects as single-agent therapies. In the present review, we highlight emerging
      information about the redundant and specific functions of PARP-1 and PARP-2 in
      genome surveillance and DNA repair pathways. Understanding these roles might
      provide invaluable clues to design new cancer therapeutic approaches. In
      addition, we provide an overview of ongoing clinical trials with PARP inhibitors
      and the value of PARP-1 and PARP-2 expression as prognostic biomarkers in cancer.

PMID- 21968706
TI  - Breast Feeding Practice among Medical Women in Nigeria.
AB  - BACKGROUND: Health care workers are important in the promotion, protection and
      support of breast feeding. Their ability to do this may be influenced by their
      knowledge, personal experiences and work.  PATIENTS AND METHOD: The breast
      feeding experience of 36 female medical doctors who had babies within the
      preceding two years and had resumed work was evaluated using a semi-structured
      self administered questionnaire.  RESULT: All respondents knew that babies should
      be exclusively breast fed for the first six months of life but only 60% knew that
      breast feeding should continue until two years. The exclusive breast feeding rate
      for the studied doctors was 11.1%. Before their babies were six months old, about
      75% of respondents had resumed work whilst over 50% had started taking calls.
      Most could not breast feed during working or call hours. Alternative feeds during
      working or call hours included expressed breast milk in 34.4% and infant formula
      in 21.9%. Feeding bottle was the major method (77.4%) for feeding these
      alternatives. Work schedule was rearranged to allow breast feeding in only 27.3%
      of respondents.  CONCLUSION: Failure to carry out exclusive breast feeding, the
      use of infant formula and feeding bottles (rather than cup feeding) are practices
      that may be inimical to the practice of breast feeding in society in general. The
      suboptimal breast feeding experience in these doctors and the identified
      knowledge deficits may limit their effectiveness in promoting and supporting
      breast feeding among their patients and communities. Female medical personnel
      should be empowered to carry out optimal feeding of their own infants.

PMID- 21968704
TI  - Phenolic composition of Tempranillo wines following early defoliation of the
      vines.
AB  - BACKGROUND: Early defoliation is a viticultural practice aimed at crop control.
      So far, the impact of early leaf removal on the monomeric phenolic composition of
      wines has not been explored. This study examines the effects of early defoliation
      on the phenolic profile and content in Tempranillo wines. The influence of the
      defoliation method (manual vs mechanical) and the timing of leaf removal (pre
      bloom vs fruit set) was investigated. RESULTS: Over two consecutive seasons, 2007
      and 2008, the monomeric phenolic composition in Tempranillo wines was studied by
      high-performance liquid chromatography with photodiode array detection, and 22
      compounds were identified and quantified. Overall, early defoliation led to wines
      more intensely coloured, of higher alcohol content and with larger concentrations
      of hydroxycinnamic acids, flavonols and anthocyanins (in 2008 only for mechanical
      treatments). In the absence of fungal infection, resveratrol was found to
      increase in wines corresponding to early defoliation treatments. The method of
      leaf removal seemed to be more critical than the timing of intervention, and
      larger effects on wine phenolic composition were observed for mechanical
      treatments. CONCLUSION: Early defoliation proved to be an effective technique for
      improving the phenolic composition of Tempranillo wines, by favouring the
      accumulation of hydroxycinnamics, flavonols and anthocyanins. This is an
      important achievement, as wine quality is often described by its colour and
      phenolic attributes.

PMID- 21968707
TI  - A novel marker design for magnetic marker monitoring in the human
      gastrointestinal tract.
AB  - Magnetic marker monitoring (MMM) is a technique to determine the motility of the
      gastrointestinal tract and to observe the dissolution of pharmaceutical
      compounds. Today's magnetic markers usually consist of magnetized magnetite.
      Because of their weak magnetic fields, highly sensitive sensor systems are
      required. For a wider class of applications, stronger markers and more flexible
      measurement setups are necessary. In this paper, a novel marker design is
      introduced. This marker comprises one permanent magnet and a compartment of iron
      powder in a magnetically unstable configuration. During dissolution of the
      pharmaceuticals, the powder is redistributed around the magnet, thereby altering
      the externally measured magnetic induction. Based on this design, magnetically
      marked tablets and capsules were prepared and their magnetic field during
      dissolution was observed. Magnetic induction values were between 16 and 0.2  MUT
      at distances of 5-30  cm, which is considerably higher compared to the pico-Tesla
      range of conventional markers. During dissolution, the magnetic induction
      decreased by between 14% and 27%. These values could be confirmed in detailed
      finite element method simulations. In conclusion, the present results indicate
      that our novel marker design is well suited for MMM with more flexible sensor
      technologies, such as magnetoresistive sensors.

PMID- 21968708
TI  - Toward a multiscale model of the uterine electrical activity.
AB  - A comprehensive multiscale model of the uterine muscle electrical activity would
      permit understanding the important link between the genesis and evolution of the
      action potential at the cell level and the process leading to labor.
      Understanding this link can open the way to more effective tools for the
      prediction of labor and prevention of preterm delivery. A first step toward the
      realization of such a model is presented here. By using as starting point a
      previously published model of the generation of the uterine muscle action
      potential at the cell level, a significant reduction of the model complexity is
      here achieved in order to simulate 2-D propagation of the cellular activity at
      the uterine tissue level, for tissue strips of arbitrary dimension. From the
      obtained dynamic behavior of the electrical activity simulated at the tissue
      level, the use of a previously validated volume conductor model at the organ
      level permits us to simulate the electrohysterogram as recorded on the abdominal
      surface by an electrode array. Qualitative evaluation of the model at the cell
      level and at the organ level confirms the potential of the proposed multiscale
      approach for further refinement and extension aiming at clinical application.

PMID- 21968709
TI  - Identification of constant-posture EMG-torque relationship about the elbow using
      nonlinear dynamic models.
AB  - The surface electromyogram (EMG) from biceps and triceps muscles of 33 subjects
      was related to elbow torque, contrasting EMG amplitude (EMGsigma) estimation
      processors, linear/nonlinear model structures, and system identification
      techniques. Torque estimation was improved by 1) advanced EMGsigma processors
      (i.e., whitened, multiple-channel signals); 2) longer duration training sets (52
      s versus 26 s); and 3) determination of model parameters via pseudoinverse and
      ridge regression methods. Dynamic, nonlinear parametric models that included
      second- or third-degree polynomial functions of EMGsigma outperformed linear
      models and Hammerstein/Weiner models. A minimum error of 4.65 +/- 3.6% maximum
      voluntary contraction (MVC) flexion was attained using a third-degree polynomial,
      28th-order dynamic model, with model parameters determined using the
      pseudoinverse method with tolerance 5.6 * 10 (-3) on 52 s of four-channel
      whitened EMG data. Similar performance (4.67 +/- 3.7% MVC flexion error) was
      realized using a second-degree, 18th-order ridge regression model with ridge
      parameter 50.1.

PMID- 21968710
TI  - Functionalized nanowire-based antigen detection using frequency-based signals.
AB  - As part of clinical diagnosis, a clinician is required to detect disease causing
      antigens, bacteria, or viruses in serum, saliva, or other biological samples.
      Usually, this requires the sample to be sent to a pathology laboratory for
      analysis. Silicon nanowires can be made into sensitive molecular sensors. When
      being functionalized with antibodies, they are capable of detecting femto molar
      concentrations of antigens in real time. Biological molecules at a pH different
      from their isoelectric point exhibit a net charge. When an antigen attaches to
      the antibody on the nanowire, the net charged on the antigen displaces free
      carriers in the nanowire changing its conductance. To date, detection methods
      have been based upon directly measuring the change in dc conductance. This is
      difficult and requires sensitive low-noise amplifiers and high-resolution analog
      to-digital converters. This is not ideal for low-cost and highly integrated
      systems. In this paper, it is demonstrated that nanowires exhibit an ac-transfer
      function that resembles that of a high-pass filter. To the authors' knowledge,
      this is the first time this effect has been reported. Furthermore, it is
      illustrated that as molecules with a higher net charge attach to the nanowire and
      displace more charge carriers within the nanowire channel, the filter's corner
      frequency decreases. This property of silicon nanowires is exploited to build a
      low-cost real-time antigen detection system.

PMID- 21968711
TI  - The concurrent validity and sensitivity of change of the German version of the
      health of the nation outcome scales in a psychiatric inpatient setting.
AB  - BACKGROUND: The Health of the Nation Outcome Scales (HoNOS) were developed to
      assess the severity of a mental illness. They are used as outcome measures in
      different countries, and are meanwhile translated from the original English
      version into many languages, among others into German (HoNOS-D). We conducted a
      study in order to estimate the concurrent validity and sensitivity to change
      using clinical parameters as ICD-10 diagnoses, as well as the Clinical Global
      Impression Scale (CGI), and the Association for Methodology and Documentation in
      Psychiatry (AMDP) psychopathology scale, a frequently used psychopathological
      rating system, in a representative clinical sample. SAMPLING AND METHODS: Data on
      the three instruments (CGI, AMDP, HoNOS-D) were collected at admission and
      discharge of 100 psychiatric inpatients using a representative clinical sample.
      Experienced clinicians completed the CGI, AMDP and HoNOS-D. Descriptive and
      comparative data analyses were performed. We estimated the concurrent validity by
      calculating correlations between the HoNOS and other scales. Secondly, we
      examined the differences between HoNOS scores related to diagnoses and
      demographic parameters. Thirdly we calculated change criteria and outcome effect
      size for the HoNOS. RESULTS: Even in a small clinical sample (n = 100), the HoNOS
      D items are highly correlated with the corresponding AMDP syndromes (p < 0.003).
      The HoNOS-D score is associated with the CGI score (p < 0.01). Correlations of
      HoNOS symptoms, behavior and impairment items with AMDP syndromes as well as
      differences in diagnoses were appropriate and comprehensible as regards clinical
      content, and change on the HoNOS total score is statistically significant (t =
      6.57, d.f. = 89, p < 0.0001). CONCLUSION: This study is the first to investigate
      the concurrent validity of HoNOS-D concerning psychopathology using the AMDP
      rating system in a clinical sample of patients with mental disorders in an
      inpatient setting. HoNOS-D can be recommended for routinely screening outcomes in
      inpatient psychiatric settings. Our analysis showed that HoNOS-D covers
      psychopathology corresponding to the AMDP rating system. A limitation of the
      study is that the study sample comprised only an inpatient population; there may
      well be differences compared to an outpatient sample.

PMID- 21968712
TI  - TGF-beta1 re-programs TLR4 signaling in L. donovani infection: enhancement of SHP
      1 and ubiquitin-editing enzyme A20.
AB  - Visceral leishmaniasis (VL), caused by Leishmania donovani, is a major health
      concern in India. It represents T-helper type 2 (Th2) bias of cytokines in active
      state and Th1 bias at cure. However, the role of the parasite in regulating Toll
      like receptor (TLR)-mediated macrophage activation in VL patients remains
      elusive. In this report, we demonstrated that later stages of L. donovani
      infection rendered tolerance to macrophages, leading to incapability for the
      production of inflammatory cytokines like tumor necrosis factor (TNF)-alpha and
      interleukin (IL)-1beta in response to TLR stimulation. Overexpression of
      transforming growth factor (TGF)-beta(1), but not IL-10, resulted in suppressed
      lipopolysaccharide (LPS)-induced production of TNF-alpha and downregulation of
      TLR4 expression in L. donovani-infected macrophages. Recombinant human (rh)TGF
      beta(1) markedly enhanced tyrosine phosphatase (Src homology region 2 domain
      containing phosphatase-1) activity, but inhibited IL-1 receptor-activated kinase
      (IRAK)-1 activation. Addition of neutralizing TGF-beta(1) antibody reversed these
      effects, and thus suggesting the pivotal role of TGF-beta(1) in promoting
      refractoriness for LPS in macrophages. Surprisingly, the use of a tyrosine
      phosphatase inhibitor (sodium orthovanadate, Na(3)VO(4)) promoted IRAK-1
      activation, confirming the negative inhibitory role of tyrosine phosphatase in
      macrophage activation. Furthermore, rhTGF-beta(1) induced tolerance in infected
      macrophages by reducing inhibitory protein (IkappaBalpha) degradation in a time
      dependent manner. In addition, short interfering RNA studies proved that
      overexpression of A20 ubiquitin-editing protein complex induced inhibitory
      activity of TGF-beta(1) on LPS-mediated nuclear factor-kappaB activation. Thus,
      these findings suggest that TGF-beta(1) promotes overexpression of A20 through
      tyrosine phosphatase activity that ensures transient activation of inflammatory
      signaling pathways in macrophages in active L. donovani infection.

PMID- 21968713
TI  - Toll-like receptor 9 mediates oral bacteria-induced IL-8 expression in gingival
      epithelial cells.
AB  - Previously, we reported that various oral bacteria regulate interleukin (IL)-8
      production differently in gingival epithelial cells. The aim of this study was to
      characterize the pattern recognition receptor(s) that mediate bacteria-induced IL
      8 expression. Among ligands that mimic bacterial components, only a Toll-like
      receptor (TLR) 9 ligand enhanced IL-8 expression as determined by ELISA. Both
      normal and immortalized human gingival epithelial (HOK-16B) cells expressed TLR9
      intracellularly and showed enhanced IL-8 expression in response to CpG
      oligonucleotide. The ability of eight strains of four oral bacterial species to
      induce IL-8 expression in HOK-16B cells, and their invasion capacity were
      examined in the absence or presence of 2% human serum. The ability of purified
      bacterial DNA (bDNA) to induce IL-8 was also examined. Six out of eight strains
      increased IL-8 production in the absence of serum. Usage of an endosomal
      acidification blocker or a TLR9 antagonist inhibited the IL-8 induction by two
      potent strains. In the presence of serum, many strains lost the ability to induce
      IL-8 and presented substantially reduced invasion capacity. The IL-8-inducing
      ability of bacteria in the absence or presence of serum showed a strong positive
      correlation with their invasion index. The IL-8-inducing ability of bacteria in
      the absence of human serum was also correlated with the immunostimulatory
      activity of its bDNA. The observed immunostimulatory activity of the bDNA could
      not be linked to its CpG motif content. In conclusion, oral bacteria induce IL-8
      in gingival epithelial cells through TLR9 and the IL-8-inducing ability depends
      on the invasive capacity and immunostimulating DNA.

PMID- 21968714
TI  - The effectiveness of patient control analgesia in the treatment of acute
      traumatic pain in the emergency department:  a randomized controlled trial.
AB  - INTRODUCTION: Pain seems to be one of the most frequent complaints in the
      emergency department, however pain control is often suboptimal as seen by many
      audits. We conducted a study to find out whether the use of patient control
      analgesia (PCA) is effective in controlling acute pain in the emergency
      department METHODOLOGY: This was a randomized controlled trial conducted in the
      emergency departments of two tertiary centres over a period of 1 year. Patients
      were randomized into two groups. The study and the control groups were given
      analgesia through the PCA system and boluses of analgesia through titration
      method, respectively. Pain levels were measured using the Visual Analogue Scale
      at 15 min intervals. Any adverse events and total morphine dose for each group
      were recorded. Finally, within 24 h, these patients were given questionnaires
      regarding their experience with regards to pain relief encountered. RESULTS: A
      total of 47 patients were enrolled. The Visual Analogue Score change over 120 min
      for PCA and Morphine bolus groups were 5.921 [SD+/-1.656] and 4.834 (SD+/-1.797),
      respectively (P<0.001). However the total dosage of morphine consumed by both
      groups were statistically insignificant; PCA 7.95 mg (SD+/-2.44) versus bolus
      8.10 (SD+/-0.99) (P=0.06). The satisfaction questionnaire also revealed that the
      PCA group of patients was more satisfied using this method of pain relief.
      CONCLUSION: PCA provides more effective pain relief and patient satisfaction when
      compared with the conventional method of bolus intravenous injection for the
      relief of traumatic pain in the emergency department setting.

PMID- 21968721
TI  - Protective predictors of alcohol use trajectories among Canadian Aboriginal
      youth.
AB  - Some Aboriginal youth are at disproportionate risk of using substances and
      developing abuse and dependence disorders. However, not all Aboriginal youth
      misuse substances and limited research has examined the protective factors
      conferring against substance use among these youth. The present study aimed to
      identify protective factors related to the alcohol use trajectories from early
      adolescence to emerging adulthood among off-reserve Canadian Aboriginal youth.
      Participants (N = 330; 50.3% male) aged 12-23 were selected from cycles 2-7 of
      Statistics Canada's NLSCY. Multilevel modeling was employed to identify
      protective factors for two constructs of alcohol use. Participation in weekly
      activities and optimism were found to be protective for both the frequency of
      alcohol use and heavy drinking trajectories. Attendance of religious services was
      also found to be protective for heavy drinking behaviors. In contrast, positive
      peer relationships were a risk factor for frequency of alcohol use, but not heavy
      drinking. The results provide preliminary evidence of important developmental
      factors to integrate into substance use intervention programs targeting
      Aboriginal youth.

PMID- 21968722
TI  - Automatic detection and segmentation of lymph nodes from CT data.
AB  - Lymph nodes are assessed routinely in clinical practice and their size is
      followed throughout radiation or chemotherapy to monitor the effectiveness of
      cancer treatment. This paper presents a robust learning-based method for
      automatic detection and segmentation of solid lymph nodes from CT data, with the
      following contributions. First, it presents a learning based approach to solid
      lymph node detection that relies on marginal space learning to achieve great
      speedup with virtually no loss in accuracy. Second, it presents a computationally
      efficient segmentation method for solid lymph nodes (LN). Third, it introduces
      two new sets of features that are effective for LN detection, one that self
      aligns to high gradients and another set obtained from the segmentation result.
      The method is evaluated for axillary LN detection on 131 volumes containing 371
      LN, yielding a 83.0% detection rate with 1.0 false positive per volume. It is
      further evaluated for pelvic and abdominal LN detection on 54 volumes containing
      569 LN, yielding a 80.0% detection rate with 3.2 false positives per volume. The
      running time is 5-20 s per volume for axillary areas and 15-40 s for pelvic. An
      added benefit of the method is the capability to detect and segment conglomerated
      lymph nodes.

PMID- 21968723
TI  - Regional spread and control of vancomycin-resistant Enterococcus faecium and
      Enterococcus faecalis in Kyoto, Japan.
AB  - The purpose of this investigation was to control the post-outbreak prevalence of
      vancomycin-resistant enterococci (VRE) in the affected Kyoto region. The study
      period was from 2005 to 2010. Faecal samples were subjected to VRE screening, and
      vancomycin resistance genes were detected by polymerase chain reaction (PCR). The
      genotype was determined by pulsed-field gel electrophoresis (PFGE) of genomic DNA
      digested with SmaI and by multilocus sequence typing (MLST). A VRE control
      programme was established in 2006, consisting of a laboratory-based faecal VRE
      screening system, annual surveillance of hospital inpatients and the promotion of
      adequate infection control measures. vanA-Enterococcus faecium, vanB-E. faecium
      and vanB-E. faecalis were detected at 35, 12 and 5 hospitals, respectively.
      Genotype analysis revealed that all of the vancomycin-resistant E. faecium
      isolates obtained since 2005 belonged to ST78, and that clonally related vanB-E.
      faecalis of ST64 had spread to three hospitals. The rate of faecal VRE carriage
      among the patients enrolled in the annual surveillance increased until 2007, when
      it reached 24 (1.2%) of the 2,035 enrolled patients. The rate began to decrease
      in 2008 and, by 2010, reached a low of 4 (0.17%) of the 2,408 enrolled patients.
      While VRE did spread within the Kyoto region, the VRE control programme succeeded
      in controlling the overall VRE spread.

PMID- 21968724
TI  - Genetic diversity of Annona  crassiflora (Annonaceae) in northern Minas Gerais
      State.
AB  - Genetic  diversity analyses of tropical tree species are relevant to landscape 
      management, plant genetic resource inventory, and biological conservation of 
      threatened species. Annona crassiflora is an endangered fruit tree  native to the
      Cerrado biome that is threatened by reduction of natural  populations and fruit
      extraction. We examined the intra- and interpopulational  genetic diversity of
      this species in the northern region of Minas Gerais State.  Seventy-two
      individuals from four natural populations were genotyped using RAPD  markers. We
      found moderate genetic diversity among populations, with Shannon's I index
      varying between 0.31 and 0.44, and Nei's genetic diversity (H(E)) for the 
      population set equal to 0.31. AMOVA indicated a greater genetic variation  within
      (77.38%) rather than among populations (22.62%), tending towards  isolation by
      distance (Mantel's r = 0.914; P = 0.089). Nei's genetic  identity estimates among
      populations revealed a hierarchical pattern of genetic  similarity of form [(CA1,
      CA2), MC], [(GM)], corroborating the high genetic  differentiation between
      spatially isolated populations.

PMID- 21968725
TI  - Improved thermostable alpha-amylase activity of Bacillus amyloliquefaciens by low
      energy ion implantation.
AB  - Thermostable  alpha-amylase is of  great importance in the starch fermentation
      industry; it is extensively used in the  manufacture of beverages, baby foods,
      medicines, and pharmaceuticals. Bacillus amyloliquefaciens produces thermostable
      alpha-amylase; however,  production of thermostable alpha-amylase  is limited.
      Ion-beam implantation is an effective method for mutation breeding  in microbes.
      We conducted ion-beam implantation experiments using two different  ions, Ar(+)
      and N(+), to  determine the survival rate of and dose effect on a high alpha
      amylase activity strain of B.  amyloliquefaciens that had been isolated from soil
      samples. N(+) implantation  resulted in a higher survival rate than Ar(+)
      implantation.  The optimum implantation dose was 2.08 * 10(15) ions/cm(2). Under 
      this implantation condition, we obtained a thermally and genetically stable 
      mutant alpha-amylase  strain (RL-1) with high enzyme activity for degrading alpha
      amylase. Compared to the parental  strain (RL), the RL-1 strain had a 57.1%
      increase in alpha-amylase activity. We conclude that  ion implantation in B.
      amyloliquefaciens can produce strains with  increased production of thermostable
      alpha-amylase.

PMID- 21968726
TI  - Effect of pregnancy on the genetic evaluation of dairy cattle.
AB  - We  investigated the effect of stage of pregnancy on estimates of breeding values
      for milk yield and milk persistency in Gyr and Holstein dairy cattle in Brazil. 
      Test-day milk yield records were analyzed using random regression models with  or
      without the effect of pregnancy. Models were compared using residual  variances,
      heritabilities, rank correlations of estimated breeding values of  bulls and
      cows, and number of nonpregnant cows in the top 200 for milk yield  and milk
      persistency. The estimates of residual variance and heritabilities obtained  with
      the models with or without the effect of pregnancy were similar for the  two
      breeds. Inclusion of the effect of pregnancy in genetic evaluation models  for
      these populations did not affect the ranking of cows and sires based on  their
      predicted breeding values for 305-day cumulative milk yield. In contrast,  when
      we examined persistency of milk yield, lack of adjustment for the effect  of
      pregnancy overestimated breeding values of nonpregnant cows and cows with a  long
      days open period and underestimated breeding values of cows with a short  days
      open period. We recommend that models include the effect of days of  pregnancy
      for estimation of adjustment factors for the effect of pregnancy in  genetic
      evaluations of Dairy Gyr and Holstein cattle.

PMID- 21968727
TI  - Association of eNOS gene polymorphisms with essential hypertension in the Han
      population in southwestern China.
AB  - Endothelial  nitric oxide synthase (eNOS) plays an important role in maintaining
      blood  pressure homeostasis and vascular integrity. Polymorphisms in the eNOS
      gene  have been found to be associated with hypertension in different human 
      populations, including Northern and Southern Chinese Han populations. To  examine
      the relationship of three eNOS gene polymorphisms, T-786C  (rs2070744), G894T
      (rs1799983), and G10T (rs7830), with hypertension in the Han  population in
      southwestern China, we carried out a study of the genotypes of  three SNPs in 510
      hypertensive and 510 normotensive subjects from the Yunnan  Province by using PCR
      RFLP and sequencing. Our SNP analyses showed that the  distribution of the T-786C
      polymorphism did not differ between patients and  controls, and that G894T and
      G10T are significantly associated with  hypertension in females, adjusted for
      covariates. Compared with the other  haplotypes, haplotype H1 (TGG), carrying
      protective 10G and 894G alleles,  significantly decreased the risk of increased
      essential hypertension in  females, with an odds ratio of 0.68 (P = 10(-5)).
      These results  suggest that the eNOS polymorphism is one of the factors
      contributing to  the predisposition for essential hypertension in the Han
      population in  southwestern China.

PMID- 21968728
TI  - Lack of an association between a single nucleotide polymorphism in the bovine
      myogenic determination 1 (MyoD1) gene and meat quality traits in indigenous
      Chinese cattle breeds.
AB  - The  myogenic determination 1 (MyoD1) gene is a member of the MyoD gene family.
      It  encodes for skeletal muscle-specific transcription factors containing highly 
      conserved basic helix-loop-helix regions that perform important roles in the 
      initiation, maintenance, and regulation of phenotypic traits. We investigated a 
      new single nucleotide polymorphism (SNP) in the MyoD1 gene to evaluate whether 
      this polymorphism affects meat quality traits in five Chinese indigenous cattle 
      breeds, namely Qinchuan (QC), Xia-Nan (XN), Nan-yang (NY), Luxi (LX), and  Jia
      xian red (JXR). A C->G transversion at position 624 was detected in exon 1  of
      the MyoD1 gene; it causes an amino acid substitution ((624)serine/(624)cysteine).
      Least squares analysis showed that this SNP is not significantly associated 
      with back fat thickness, eye muscle area, intramuscular fat, or marbling. The 
      A/B allelic frequencies in the five breeds were 0.810/0.189, 0.779/0.220, 
      0.768/0.231, 0.820/0.180, and 0.801/0.198, respectively. Based on the chi(2)
      test,  the genotype distributions of four cattle breeds (LX, NY, QC, and XN) did
      not  agree with Hardy-Weinberg equilibrium (P < 0.05); one breed (JXR) did not 
      deviate significantly from Hardy-Weinberg equilibrium (P > 0.05). The  genotypic
      frequencies among all five cattle breeds showed moderate diversity  (0.25 <
      polymorphism information content < 0.5). We concluded that the  C624G SNP of the
      MyoD1 gene does not influence meat quality traits in  indigenous Chinese cattle
      breeds; however, this SNP could be included in breed  composition and population
      admixture analyses due to the marked differences in  allelic frequencies among
      these five breeds.

PMID- 21968729
TI  - Isolation and characterization of microsatellite markers for the White Cloud
      Mountain  minnow (Tanichthys albonubes) in wild and cultured populations.
AB  - We developed 12 microsatellite loci for the endangered  minnow species,
      Tanichthys albonubes, using PCR-based isolation of  microsatellite arrays. These
      new markers were tested in 26 individuals from a  wild population collected from
      Guangzhou in China and 26 individuals from a  cultured strain. The number of
      alleles ranged from two to nine and the expected  heterozygosity from 0.177 to
      0.853. The wild population had significantly  higher allelic richness than the
      cultured strain, with a mean allelic richness  of 5.52 (range = 3.69-8.64) and
      3.13 (range = 1.99-5.73) for the wild  population and the cultured strain,
      respectively. No evidence of a recent  bottleneck was detected in the wild
      population, but it was found in the  cultured strain based on the BOTTLENECK
      test. These primers can be used to  understand the demography and to examine
      genetic differences between the  cultured T. albonubes strains and wild
      populations to help determine  conservation and reintroduction strategies.

PMID- 21968730
TI  - Modeling of crossbred cattle growth, comparison  between cubic and piecewise
      random regression models.
AB  - Two analyses, cubic and piecewise random regression,  were conducted to model
      growth of crossbred cattle from birth to about two  years of age, investigating
      the ability of a piecewise procedure to fit growth  traits without the
      complications of the cubic model. During a four-year period  (1994-1997) of the
      Australian "Southern Crossbreeding Project", mature Hereford  cows (N = 581) were
      mated to 97 sires of Angus, Belgian Blue, Hereford, Jersey,  Limousin, South
      Devon, and Wagyu breeds, resulting in 1141 steers and heifers  born over four
      years. Data included 13 (for steers) and eight (for heifers)  live body weight
      measurements, made approximately every 50 days from birth  until slaughter. The
      mixed model included fixed effects of sex, sire breed, age  (linear, quadratic
      and cubic), and their interactions between sex and sire  breed with age. Random
      effects were sire, dam, management (birth location,  year, post-weaning groups),
      and permanent environmental effects and for each of  these when possible, their
      interactions with linear, quadratic and cubic growth.  In both models, body
      weights of all breeds increased over pre-weaning period,  held fairly steady
      (slightly flattening) over the dry season then increased  again towards the end
      of the feedlot period. The number of estimated parameters  for the cubic model
      was 22 while for the piecewise model it was 32. It was  concluded that the
      piecewise model was very similar to the cubic model in the  fit to the data; with
      the piecewise model being marginally better. The  piecewise model seems to fit
      the data better at the end of the growth period.

PMID- 21968731
TI  - Isolation and characterization of 16 novel  microsatellite loci in two inbred
      strains of the Chinese hamster (Cricetulus griseus).
AB  - The  Shanyi inbred A and E strains of the Chinese hamster are widely used in 
      biomedical research, but detailed genetic characterization has been lacking. We 
      developed microsatellite markers that could be used for genetic diversity 
      analysis and linkage map construction. We isolated and characterized 16 novel 
      microsatellite loci from a microsatellite-enriched genomic DNA library. These 
      loci were genotyped in 48 animals from the two strains, and the polymorphic 
      information content was determined. In the Shanyi A and E populations, 14 and  15
      loci were found to be polymorphic, respectively, with polymorphic information 
      content ranging from 0.1393 to 0.8082 and from 0.1109 to 0.7397, respectively.  A
      total of 115 alleles were found for the 16 microsatellite loci in the two 
      populations; the mean observed heterozygosity (H(O)) was  0.5191 and 0.4333 for
      the A and E populations, respectively, indicating marked  genetic variation
      within the two populations. Correspondingly, the F(ST) values  ranged from 0.002
      to 0.9253, with an overall mean of 0.1935, indicating  significant genetic
      difference between the two strains. The population  differentiation levels were
      substantiated by Nei's genetic distance and full  Bayesian analyses computed with
      STRUCTURE. Despite the genetic diversity and  differentiation within and between
      the two inbred populations, the 48  individuals were correctly allocated into
      their original populations with high statistical  confidence based on these 16
      microsatellite loci. These novel microsatellite  loci should be useful genetic
      markers for these two Chinese hamster inbred  strains.

PMID- 21968732
TI  - Energy-efficient FastICA implementation for biomedical signal separation.
AB  - This paper presents an energy-efficient fast independent component analysis
      (FastICA) implementation with an early determination scheme for eight-channel
      electroencephalogram (EEG) signal separation. The main contributions are as
      follows: (1) energy-efficient FastICA using the proposed early determination
      scheme and the corresponding architecture; (2) cost-effective FastICA using the
      proposed preprocessing unit architecture with one coordinate rotation digital
      computer-based eigenvalue decomposition processor and the proposed one-unit
      architecture with the hardware reuse scheme; and (3) low-computation-time FastICA
      using the four parallel one-units architecture. The resulting power dissipation
      of the FastICA implementation for eight-channel EEG signal separation is 16.35 mW
      at 100 MHz at 1.0 V. Compared with the design without early determination, the
      proposed FastICA architecture implemented in united microelectronics corporation
      90 nm 1P9M complementary metal-oxide-semiconductor process with a core area of
      1.221 * 1.218 mm2 can achieve average energy reduction by 47.63%. From the post
      layout simulation results, the maximum computation time is 0.29 s.

PMID- 21968733
TI  - Adaptive evolutionary artificial neural networks for pattern classification.
AB  - This paper presents a new evolutionary approach called the hybrid evolutionary
      artificial neural network (HEANN) for simultaneously evolving an artificial
      neural networks (ANNs) topology and weights. Evolutionary algorithms (EAs) with
      strong global search capabilities are likely to provide the most promising
      region. However, they are less efficient in fine-tuning the search space locally.
      HEANN emphasizes the balancing of the global search and local search for the
      evolutionary process by adapting the mutation probability and the step size of
      the weight perturbation. This is distinguishable from most previous studies that
      incorporate EA to search for network topology and gradient learning for weight
      updating. Four benchmark functions were used to test the evolutionary framework
      of HEANN. In addition, HEANN was tested on seven classification benchmark
      problems from the UCI machine learning repository. Experimental results show the
      superior performance of HEANN in fine-tuning the network complexity within a
      small number of generations while preserving the generalization capability
      compared with other algorithms.

PMID- 21968734
TI  - Physiologically based pharmacokinetic tissue compartment model selection in drug
      development and risk assessment.
AB  - A well-stirred tank (WST) has been the predominant flow-limited tissue
      compartment model in physiologically based pharmacokinetic (PBPK) modeling.
      Recently, we developed a two-region asymptotically reduced (TAR) PBPK tissue
      compartment model through an asymptotic approximation to a two-region vascular
      extravascular system to incorporate more biophysical detail than the WST model.
      To determine the relevance of a flow-limited TAR (F-TAR) approach, 75
      structurally diverse drugs were evaluated herein using a priori predicted
      tissue:plasma partition coefficients along with hybrid and whole-body PBPK of
      eight rat tissues to determine the impact of model selection on simulation and
      optimization. Simulations showed that the F-TAR model significantly improved the
      ability to predict drug exposure, with hybrid and whole-body WST model error
      approaching 50% for tissues with larger vascular volumes. When optimization was
      used to fit F-TAR and WST models to pseudo data, WST-optimized drug partition
      coefficients more appropriately represented curve-fitting parameters rather than
      biophysically meaningful partition coefficients. Median F-TAR-optimized error
      ranged from -0.4% to +0.3%, whereas WST-optimized median error ranged from -22.2%
      to +1.8%. These studies demonstrated that the use of F-TAR represents a more
      accurate, biophysically realistic PBPK tissue model for predicting tissue
      exposure to drug and that it should be considered for use in drug development and
      regulatory review.

PMID- 21968735
TI  - Recombinant human CD137L for cancer immunotherapy: effects of different fusions
      and linkers on its activity.
AB  - Co-stimulatory molecules can be efficiently produced as a recombinant protein in
      E. coli with a large range of applications in the fields of immunotherapy.
      However, whether, different fusions that would affect their functions have rarely
      been analyzed. To explore the effects of different fusions and linkers on the
      molecular conformation and activity of CD137 ligand (CD137L), a recombinant human
      CD137L protein (rhCD137L) library, which consists of the entire extracellular
      domain of human CD137L fused to N- or C-terminal His-tag through different
      linkers, was constructed and all rhCD137Ls were, respectively, expressed in E.
      coli BL21 (DE3) strain carrying a chaperone plasmid pG-Tf2. After purification of
      the soluble rhCD137Ls, the recombinant fusion proteins could markedly promote the
      growth of activated T cells, but their effects on cytokine productions were
      different from each other. The present work indicated that, although all
      rhCD137Ls have desired biological activity, different fusions and linkers did
      affect their structures and functions. Consequently, rational design of a library
      is a necessary and feasible approach for fusion proteins in order to obtain a
      satisfactory drug candidate for further development.

PMID- 21968736
TI  - Macular folds after retinal detachment surgery: the possible impact of outpatient
      surgery.

PMID- 21968739
TI  - Early leaf removal impact on volatile composition of Tempranillo wines.
AB  - BACKGROUND: Early defoliation is a very innovative technique in viticulture used
      for yield management. The effects of early leaf removal performed manually and
      mechanically at two different phenological stages, pre-bloom and fruit set, on
      the volatile composition of Tempranillo (Vitis vinifera L.) wines were studied.
      Volatiles were identified and quantified by gas chromatography. RESULTS: Early
      leaf removal only modified the total concentrations of C6 compounds and acetates,
      whereas total alcohols, esters, volatile acids and terpenes remained generally
      unaffected. Early defoliation induced a significant reduction in C6 compounds and
      increased the concentrations of acetates in Tempranillo wines. An effect of
      timing (pre-bloom vs fruit set) alone was observed for all acetates analysed.
      Regarding the method of defoliation (manual vs mechanical), significant
      differences in some ethyl ester (ethyl-2-methylbutyrate and ethyl octanoate) and
      volatile acid concentrations were observed among treatments. Ethyl octanoate, 2
      phenylethyl acetate, 3-methylbutyl acetate and hexanoic acid, with OAV (odour
      activity value) > 1 and mainly fruity and floral odour descriptors, showed higher
      levels after early defoliation treatments compared with non-defoliated vines.
      Principal component analysis illustrated the difference in wines from defoliated
      and non-defoliated treatments based on their volatile composition. CONCLUSION: It
      can be concluded that early leaf removal significantly modified the wine aroma
      compounds, increasing or decreasing several of these compounds.

PMID- 21968738
TI  - The molecular genetics of sulfonylurea receptors in the pathogenesis and
      treatment of insulin secretory disorders and type 2 diabetes.
AB  - Sulfonylurea receptors (SURs) form an integral part of the ATP-sensitive
      potassium (K(ATP)) channel complex that is present in most excitable cell types.
      K(ATP) channels couple cellular metabolism to electrical activity and provide a
      wide range of cellular functions including stimulus secretion coupling in
      pancreatic beta cells. K(ATP) channels are composed of SURs and inward rectifier
      potassium channel (Kir6.x) subunits encoded by the ABCC8/9 and KCNJ8/11 genes,
      respectively. Recent advances in the genetics, molecular biology, and
      pharmacology of SURs have led to an increased understanding of these channels in
      the etiology and treatment of rare genetic insulin secretory disorders.
      Furthermore, common genetic variants in these genes are associated with an
      increased risk for type 2 diabetes. In this review we summarize the molecular
      biology, pharmacology, and physiology of SURs and K(ATP) channels, highlighting
      recent advances in their genetics and understanding of rare insulin secretory
      disorders and susceptibility to type 2 diabetes.

PMID- 21968740
TI  - Monomorphic platinum octapod and tripod nanocrystals synthesized by an iron
      nitrate modified polyol process.
AB  - Monomorphic Pt octapod and tripod nanocrystals have been successfully synthesized
      by an iron nitrate modified polyol process, in which iron nitrate has been proven
      to be vitally important for slowing down the reduction rate of Pt precursors.

PMID- 21968741
TI  - A terpyridyl-imidazole (tpy-HImzPh3) based bifunctional receptor for multichannel
      detection of Fe2+ and F- ions.
AB  - The X-ray crystal structures of the tridentate ligand, 4'-[4-(4,5-diphenyl-1H
      imidazol-2-yl)-phenyl]-[2,2':6',2'']terpyridine (tpy-HImzPh(3)) and its bis
      homoleptic iron(ii) complex of composition [Fe(tpy-HImzPh(3))(2)](2+) have been
      determined, showing that the ligand crystallized in a monoclinic form with the
      space group P2(1)/c while its Fe(II) complex crystallizes in an orthorhombic form
      with space group Fddd. Both the anion and cation binding properties of the
      receptor were thoroughly investigated in dimethylformamide-acetonitrile (1 : 9)
      solution using absorption, emission, and (1)H NMR spectral studies which revealed
      that the receptor acts as a sensor for both F(-) and Fe(2+). In the presence of
      excess F(-) ion, deprotonation of the imidazole N-H fragment of the receptor
      occurs, an event which is signaled by the development of a yellow color visible
      with the naked eye. The estimated value of the equilibrium constant of the
      receptor with F(-) is 1.9 * 10(4) M(-1). Deprotonation is also observed in the
      presence of hydroxide. The receptor also shows colorimetric and fluorimetric
      sensing ability towards Fe(2+) ions. The binding site for the metal ion in the
      system has been unambiguously established by single-crystal X-ray diffraction
      studies of the Fe(II) complex of the receptor. The influence of solvents on the
      absorption and fluorescence spectra of the receptor has been investigated in
      detail. Cyclic voltammetric (CV) and square wave voltammetric (SWV) measurements
      carried out in dimethylformamide-acetonitrile (2 : 3) provided evidence in favor
      of cation (Fe(2+)) and anion (F(-)) concentration dependent electrochemical
      responses, enabling the ligand to act as a suitable electrochemical sensor for F(
      ) and Fe(2+) ions.

PMID- 21968742
TI  - Interleukin-17-positive mast cells contribute to synovial inflammation in
      spondylarthritis.
AB  - OBJECTIVE: Studies comparing spondylarthritis (SpA) to rheumatoid arthritis (RA)
      synovitis suggest that innate immune cells may play a predominant role in the
      pathogenesis of SpA. Recent observations have indicated a marked synovial mast
      cell infiltration in psoriatic SpA. We therefore undertook the present study to
      investigate the potential contribution of mast cells to synovial inflammation in
      SpA. METHODS: Synovial tissue and fluid were obtained from patients with either
      nonpsoriatic or psoriatic SpA (n=82) and patients with RA (n=50). Synovial biopsy
      tissue was analyzed by immunostaining and used in ex vivo cultures. Synovial
      fluid was analyzed by enzyme-linked immunosorbent assay. RESULTS: We observed a
      strong and specific increase of c-Kit-positive mast cells in the synovium from
      patients with SpA compared to the synovium from patients with RA synovitis, which
      was independent of disease subtype (nonpsoriatic versus psoriatic), disease
      duration, and treatment. Staining of mast cell granules, analysis of synovial
      fluid, and results in ex vivo tissue culture did not indicate increased
      degranulation in SpA synovitis. However, mast cells expressed significantly more
      interleukin-17 (IL-17) in SpA than in RA synovitis, and mast cells constituted
      the major IL-17-expressing cell population in the SpA synovium. Ex vivo targeting
      of synovial mast cells with the c-Kit inhibitor imatinib mesylate significantly
      decreased the production of IL-17 as well as other proinflammatory cytokines in
      synovial tissue cultures. Analysis of paired pre- and posttreatment synovial
      tissue samples indicated that the mast cell/IL-17 axis in SpA was not modulated
      by effective tumor necrosis factor (TNF) blockade. CONCLUSION: The specific and
      TNF-independent increase in IL-17-expressing mast cells may contribute to the
      progression of synovial inflammation in peripheral SpA.

PMID- 21968743
TI  - Generalized biased discriminant analysis for content-based image retrieval.
AB  - Biased discriminant analysis (BDA) is one of the most promising relevance
      feedback (RF) approaches to deal with the feedback sample imbalance problem for
      content-based image retrieval (CBIR). However, the singular problem of the
      positive within-class scatter and the Gaussian distribution assumption for
      positive samples are two main obstacles impeding the performance of BDA RF for
      CBIR. To avoid both of these intrinsic problems in BDA, in this paper, we propose
      a novel algorithm called generalized BDA (GBDA) for CBIR. The GBDA algorithm
      avoids the singular problem by adopting the differential scatter discriminant
      criterion (DSDC) and handles the Gaussian distribution assumption by redesigning
      the between-class scatter with a nearest neighbor approach. To alleviate the
      overfitting problem, GBDA integrates the locality preserving principle;
      therefore, a smooth and locally consistent transform can also be learned.
      Extensive experiments show that GBDA can substantially outperform the original
      BDA, its variations, and related support-vector-machine-based RF algorithms.

PMID- 21968744
TI  - Intrinsic illumination subspace for lighting insensitive face recognition.
AB  - We introduce the intrinsic illumination subspace and its application for lighting
      insensitive face recognition in this paper. The intrinsic illumination subspace
      is constructed from illumination images of intrinsic images, which is a midlevel
      description of appearance images and can be useful for many visual inferences.
      This subspace forms a convex polyhedral cone and can be efficiently represented
      by a low-dimensional linear subspace, which enables an analytic generation of
      illumination images under varying lighting conditions. When only objects of the
      same class, such as faces, are concerned, a class-based generic intrinsic
      illumination subspace can be constructed in advance and used for novel objects of
      the same class. Based on this class-based generic subspace, we propose a lighting
      normalization method for lighting insensitive face recognition, where only a
      single input image is required. The generic subspace is used as a bootstrap
      subspace for illumination images of novel objects. Face recognition experiments
      are performed to demonstrate the effectiveness of the proposed lighting
      normalization method and verify empirically that the class-based generic subspace
      is applicable to novel objects. Our method is simple and fast, which makes it
      useful for real-time applications, embedded systems, or mobile devices with
      limited resources.

PMID- 21968747
TI  - Ultrasonographic biometry: Biparietal Diameter of Nigerian foetuses.
AB  - BACKGROUND: Foetal biparietal diameter has been studied previously in Nigerian
      foetuses but populations have been too small to make categorical conclusions
      regarding the reference values/data.  MATERIALS AND METHODS: In a cross sectional
      study, the foetal biparietal diameter (BPD) of 13,740 foetuses in Jos were
      measured with grey ultrasound machine in 13,740 Nigerian women during normal
      pregnancy and the mean BPD values for each week of pregnancy between 12 and 42
      weeks were determined.  RESULTS: The mean biparietal diameter value was 29.4mm at
      14 weeks, 49.4mm at 20 weeks, 78.4mm at 30 weeks, 91.5 at 37 weeks and 95.6mm at
      40 weeks. There was a positive relationship between gestational age and
      biparietal diameter with correlation coefficient of R(2) = 0.9996 (P < 0.001),
      and with fetal weight. The increase in BPD with increasing age in the study
      population showed a curve similar to that of Europeans.  CONCLUSIONS:
      Ultrasonographic measurement of biparietal diameter in Nigerian fetuses showed a
      linear correlation exists between BPD and gestational age, as well as BPD and
      foetal weight in normal foetuses.

PMID- 21968748
TI  - A simplified method for the generation of human osteoclasts in vitro.
AB  - Osteoclasts are large, multinucleated cells responsible for the resorption of
      mineralized bone matrix. These cells are critical players in the bone turnover
      involved in bone homeostasis. Osteoclast activity is connected to the
      establishment and expansion of skeletal metastases from a number of primary
      neoplasms. Thus, the formation and activation of osteoclasts is an area of
      research with many potential avenues for clinical translation. Past studies of
      osteoclast biology have utilized primary murine cells cultured in vitro.
      Recently, techniques have been described that involve the generation of
      osteoclasts from human precursor cells. However, these protocols are often time
      consuming and insufficient for generating large numbers of osteoclasts. We
      therefore developed a simplified protocol by which human osteoclasts may be
      easily and reliably generated in large numbers in vitro. In this study,
      osteoclasts were differentiated from bone marrow cells that had been aliquotted
      and frozen. Cells were generated by culture with recombinant macrophage colony
      stimulating factor (M-CSF) and receptor activator of NF-kappaB ligand (RANKL).
      Both human and murine RANKL were shown to efficiently generate osteoclasts,
      although higher concentrations of murine RANKL were required. Formation of
      osteoclasts was demonstrated qualitatively by tartrate-resistant acid phosphatase
      (TRAP) staining. These cells were fully functional, as confirmed by their ability
      to form resorption pits on cortical bone slices. Functional human osteoclasts can
      be difficult to generate in vitro by current protocols. We have demonstrated a
      simplified system for the generation of human osteoclasts in vitro that allows
      for large numbers of osteoclasts to be obtained from a single donor.

PMID- 21968746
TI  - Fungal biodegradation and enzymatic modification of lignin.
AB  - Lignin, the most abundant aromatic biopolymer on Earth, is extremely recalcitrant
      to degradation. By linking to both hemicellulose and cellulose, it creates a
      barrier to any solutions or enzymes and prevents the penetration of
      lignocellulolytic enzymes into the interior lignocellulosic structure. Some
      basidiomycetes white-rot fungi are able to degrade lignin efficiently using a
      combination of extracellular ligninolytic enzymes, organic acids, mediators and
      accessory enzymes. This review describes ligninolytic enzyme families produced by
      these fungi that are involved in wood decay processes, their molecular
      structures, biochemical properties and the mechanisms of action which render them
      attractive candidates in biotechnological applications. These enzymes include
      phenol oxidase (laccase) and heme peroxidases [lignin peroxidase (LiP), manganese
      peroxidase (MnP) and versatile peroxidase (VP)]. Accessory enzymes such as
      H(2)O(2)-generating oxidases and degradation mechanisms of plant cell-wall
      components in a non-enzymatic manner by production of free hydroxyl radicals
      (.OH) are also discussed.

PMID- 21968749
TI  - Genetic liability to schizophrenia measured by p300 in concordant and discordant
      monozygotic twins.
AB  - BACKGROUND: Differential effects of genes and environment can contribute to
      etiological heterogeneity in schizophrenia. Twins concordant and discordant for
      schizophrenia may differ in genetic predisposition to schizophrenia with
      concordant twins having a higher genetic liability and discordant twins having a
      lower genetic liability to schizophrenia. We aimed to investigate whether P300
      amplitude (which has been postulated as a genetic marker for schizophrenia)
      reflected this heterogeneity. SAMPLING AND METHODS: We compared P300 amplitudes
      across 36 monozygotic twin pairs (6 concordant for schizophrenia/schizoaffective
      disorder, 11 discordant and 19 healthy control pairs) performing an auditory
      oddball task, using multiple regression (age, gender, birth order, premorbid IQ
      as covariates). We further looked at the correlation between the Brief
      Psychiatric Rating Scale (BPRS) and P300 amplitude in affected twins, and
      compared concordant and discordant affected twins on the Global Assessment Scale
      (GAS). RESULTS: Multiple regression yielded a highly significant model (p =
      0.004) though the explained variance was limited (21%). The main effect of the
      group on P300 amplitude was significant (p = 0.0001): affected concordant twins
      showed a significantly lower P300 amplitude as compared to affected discordant (p
      = 0.005, Cohen's d = 1.08) and control twins (p = 0.000, d = 1.16). Discordant
      affected and unaffected twins did not differ significantly from each other or
      from control twins. P300 did not correlate significantly with the BPRS and the
      affected groups did not differ across the GAS. CONCLUSIONS: Our results provide
      evidence for etiological heterogeneity within schizophrenia pointing to different
      pathophysiological mechanisms that may underlie more and less genetically
      determined forms of schizophrenia. They also indicate that P300 correlates with a
      differing degree of genetic liability to schizophrenia independently of the
      psychopathological status and even in the presence of similar functional
      profiles.

PMID- 21968750
TI  - Obstructive sleep apnea: the most common secondary cause of hypertension
      associated with resistant hypertension.
AB  - Recognition and treatment of secondary causes of hypertension among patients with
      resistant hypertension may help to control blood pressure and reduce
      cardiovascular risk. However, there are no studies systematically evaluating
      secondary causes of hypertension according to the Seventh Joint National
      Committee. Consecutive patients with resistant hypertension were investigated for
      known causes of hypertension irrespective of symptoms and signs, including aortic
      coarctation, Cushing syndrome, obstructive sleep apnea, drugs, pheochromocytoma,
      primary aldosteronism, renal parenchymal disease, renovascular hypertension, and
      thyroid disorders. Among 125 patients (age: 52+/-1 years, 43% males, systolic and
      diastolic blood pressure: 176+/-31 and 107+/-19 mm Hg, respectively), obstructive
      sleep apnea (apnea-hypopnea index: >15 events per hour) was the most common
      condition associated with resistant hypertension (64.0%), followed by primary
      aldosteronism (5.6%), renal artery stenosis (2.4%), renal parenchymal disease
      (1.6%), oral contraceptives (1.6%), and thyroid disorders (0.8%). In 34.4%, no
      secondary cause of hypertension was identified (primary hypertension). Two
      concomitant secondary causes of hypertension were found in 6.4% of patients. Age
      >50 years (odds ratio: 5.2 [95% CI: 1.9-14.2]; P<0.01), neck circumference >=41
      cm for women and >=43 cm for men (odds ratio: 4.7 [95% CI: 1.3-16.9]; P=0.02),
      and presence of snoring (odds ratio: 3.7 [95% CI: 1.3-11]; P=0.02) were
      predictors of obstructive sleep apnea. In conclusion, obstructive sleep apnea
      appears to be the most common condition associated with resistant hypertension.
      Age >50 years, large neck circumference measurement, and snoring are good
      predictors of obstructive sleep apnea in this population.

PMID- 21968751
TI  - Predictors of decline in medication adherence: results from the cohort study of
      medication adherence among older adults.
AB  - Few data are available on the predictors of decline in antihypertensive
      medication adherence and the association of decline in adherence with subsequent
      blood pressure (BP) control. The current analysis included 1965 adults from the
      Cohort Study of Medication Adherence Among Older Adults recruited between August
      2006 and September 2007. Decline in antihypertensive medication adherence was
      defined as a >=2-point decrease on the 8-item Morisky Medication Adherence Scale
      assessed during telephone surveys 1 and 2 years after baseline. Risk factors for
      decline in adherence were collected using telephone surveys and administrative
      databases. BP was abstracted from outpatient records. The annual rate for a
      decline in adherence was 4.3% (159 participants experienced a decline). After
      multivariable adjustment, a decline in adherence was associated with an odds
      ratio (OR) for uncontrolled BP (>=140/90 mm Hg) at follow-up of 1.68 (95% CI:
      1.01-2.80). Depressive symptoms (OR: 1.84 [95% CI: 1.20-2.82]) and a high
      stressful life events score (OR: 1.68 [95% CI: 1.19-2.38]) were associated with
      higher ORs for a decline in adherence. Female sex (OR: 0.61 [95% CI: 0.42-0.88]),
      being married (OR: 0.68 [95% CI: 0.47-0.98]), and calcium channel blocker use
      (OR: 0.68 [95% CI: 0.48-0.97]) were associated with lower ORs for decline. In
      summary, a decline in antihypertensive medication adherence was associated with
      uncontrolled BP. Modifiable factors associated with decline were identified.
      Further research is warranted to determine whether interventions can prevent the
      decline in antihypertensive medication adherence and improve BP control.

PMID- 21968752
TI  - Intensified effect of adiposity on blood pressure in overweight and obese
      children.
AB  - In children, blood pressure (BP) and risk for hypertension are proportional to
      degree of adiposity. Whether the relationship to BP is similar over the full
      range of adiposity is less clear. Subjects from a cohort study (n=1111; 50% male
      and 42% black) contributed 9102 semiannual BP and height/weight assessments. The
      mean enrollment age was 10.2 years, and mean follow-up was 4.5 years. Adiposity
      was expressed as body mass index percentile, which accounted for effects of age
      and sex. The following observations were made. The effect of relative adiposity
      on BP was minimal until the body mass index percentile reached 85, beginning of
      the overweight category, at which point the effect of adiposity on BP increased
      by 4-fold. Similarly intensified adiposity effects on BP were observed in
      children aged <=10, 11 to 14 years, and >=15 years. Serum levels of the adipose
      tissue-derived hormone, leptin, together with heart rate, showed an almost
      identically patterned relation to BP to that of body mass index percentile and
      BP, thus implicating a possible mediating role for leptin. In conclusion, there
      is a marked intensification of the influence of adiposity on BP when children
      reach the categories of overweight and obese. Among the possible pathways, leptin
      may be a potentially important mediator acting through the sympathetic nervous
      system (reflected in heart rate). The findings have relevance to interventions
      designed to prevent or treat adiposity-related increases in BP and to the
      analytic approaches used in epidemiological studies.

PMID- 21968753
TI  - Central pulse pressure and aortic stiffness determine renal hemodynamics:
      pathophysiological implication for microalbuminuria in hypertension.
AB  - A significant link has been reported between aortic stiffening and renal
      microvascular damage, but the underlying mechanism remains poorly understood. We
      hypothesized that alterations in central and renal hemodynamics are responsible
      for this link. In 133 patients with hypertension, pressure waveforms were
      recorded on the radial, carotid, femoral, and dorsalis pedis arteries with
      applanation tonometry to estimate the aortic pressures and aortic (carotid
      femoral) and peripheral (carotid-radial and femoral-dorsalis pedis) pulse wave
      velocities. Flow-velocity waveforms were recorded on the renal segmental arteries
      with duplex ultrasound to calculate the resistive index (RI) as [1 - (end
      diastolic velocity/peak systolic velocity)] and on the femoral arteries to
      calculate the reverse/forward flow index and diastolic/systolic forward-flow
      ratio. Albuminuria was defined as urinary albumin/creatinine ratio >=30 mg/g of
      creatinine. The renal RI (mean: 0.65+/-0.07) was strongly correlated (P<0.001)
      with the aortic pulse pressure (r=0.62), incident pressure wave (r=0.55),
      augmented pressure (r=0.49), and aortic pulse wave velocity (r=0.51), although
      not with the mean arterial pressure or peripheral pulse wave velocities. The
      correlations remained highly significant after consideration of confounders
      including age, cholesterol, hemoglobin A(1c), and glomerular filtration rate. The
      renal RI was inversely correlated with the femoral reverse and diastolic forward
      flow indices. Both aortic pulse pressure and renal RI correlated with the urinary
      albumin/creatinine ratio independent of confounders. Each 0.1 increase in renal
      RI was associated with a 5.4-fold increase in the adjusted relative risk of
      albuminuria. In conclusion, increased aortic pulse pressure causes renal
      microvascular damage through altered renal hemodynamics resulting from increased
      peripheral resistance and/or increased flow pulsation.

PMID- 21968754
TI  - Angiotensin-converting enzyme 2 deficiency is associated with impaired
      gestational weight gain and fetal growth restriction.
AB  - Angiotensin-converting enzyme 2 (ACE2) is a key enzyme of the renin-angiotensin
      system that influences the relative expression of angiotensin II (Ang II) and Ang
      (1-7). Although ACE2 expression increases in normal pregnancy, the impact of ACE2
      deficiency in pregnancy has not been elucidated. We determined the influence of
      ACE2 deficiency on circulating and tissue renin-angiotensin system components,
      fetal and maternal growth characteristics, and maternal hemodynamics (mean blood
      pressure and cardiac output) at day 18 of gestation. Gestational body weight gain
      was lower in the ACE2 knockout (KO) versus C57BL/6 (wild-type) mice (30.3+/-4.7
      versus 38.2+/-1.0 g; P<0.001). Fetal weight (0.94+/-0.1 versus 1.24+/-0.01 g;
      P<0.01) and length (19.6+/-0.2 versus 22.2+/-0.2 mm; P<0.001) were less in KO.
      Mean blood pressure was significantly reduced in C57BL/6 with pregnancy; it was
      elevated (P<0.05) in the KO virgin and pregnant mice, and this was associated
      with an increased cardiac output in both C57BL/6 and KO pregnant mice (P<0.05).
      Plasma Ang-(1-7) was reduced in pregnant KO mice (P<0.05). Placenta Ang II levels
      were higher in KO mice (52.9+/-6.0 versus 22.0+/-3.3 fmol/mg of protein;
      P<0.001). Renal Ang II levels were greater in KO virgin mice (30.0+/-1.7 versus
      23.7+/-1.1 fmol/mg of protein; P<0.001). There was no change in the Ang-(1-7)
      levels in the KO placenta and virgin kidney. These results suggest that ACE2
      deficiency and associated elevated placenta Ang II levels impact pregnancy by
      impairing gestational weight gain and restricting fetal growth.

PMID- 21968755
TI  - Low birth weight infants do not have capillary rarefaction at birth: implications
      for early life influence on microcirculation.
AB  - Low birth weight predicts adult essential hypertension and is linked to increased
      cardiovascular mortality in adult life. A reduction in capillary density (ie,
      rarefaction) is a hallmark of essential hypertension, and evidence suggests that
      rarefaction precedes the onset of the rise in blood pressure, because it is found
      in normotensive individuals at high risk of developing hypertension, suggesting
      that rarefaction is likely to be a primary structural abnormality. We
      hypothesized that low birth weight infants would have significant capillary
      rarefaction at birth. We studied 44 low birth weight infants born to normotensive
      mothers (33 were born preterm, birth weight: 1823+/-446 g; and 11 were born at
      term, birth weight: 2339+/-177 g) and compared them with 71 infants born at term
      with normal weight (birth weight: 3333+/-519 g). We used orthogonal polarized
      spectroscopy to measure basal (ie, functional) and maximal (ie, structural) skin
      capillary densities. Low birth weight infants, whether born preterm or at term,
      had significantly higher functional capillary density (mean difference of 10.5
      capillaries per millimeter squared; 95% CI: 6.6-14.4 capillaries per millimeter
      squared; P<0.0001) and higher structural capillary density (mean difference of
      11.1 capillaries per millimeter squared; 95% CI: 7.6-14.5 capillaries per
      millimeter squared; P<0.0001) when compared with normal weight term infants. We
      conclude that low birth weight infants born to normotensive mothers do not have
      capillary rarefaction at birth. These results contradict what might have been
      predicted from the concept of the intrauterine origins of adult disease and
      suggest that microcirculatory abnormalities observed in individuals of low birth
      weight occur in postnatal life rather than during their intrauterine existence.

PMID- 21968756
TI  - Childhood obesity and blood pressure: back to the future?

PMID- 21968758
TI  - Early life microcirculation and the development of hypertension.

PMID- 21968759
TI  - Asymmetrical dimethylarginine, oxidative stress, and atherosclerosis.

PMID- 21968757
TI  - Gene transfer of neuronal nitric oxide synthase to the paraventricular nucleus
      reduces the enhanced glutamatergic tone in rats with chronic heart failure.
AB  - Our previous studies have shown that the decreased NO and increased glutamatergic
      mechanisms on sympathetic regulation within the paraventricular nucleus (PVN) may
      contribute to the elevated sympathoexcitation during chronic heart failure (CHF).
      In the present study, we investigated the effects of neuronal NO synthase (nNOS)
      gene transfer on N-methyl-D-aspartic acid receptor subunit NR(1) in the rats with
      a coronary ligation model of CHF. Adenovirus vectors encoding nNOS (AdnNOS) or
      adenovirus vectors encoding beta-galactosidase were transfected into the PVN in
      vivo. Five days after application of AdnNOS, the increased expression of nNOS
      within the PVN was confirmed by NADPH-diaphorase staining, real-time PCR, and
      Western blot. In anesthetized rats, AdnNOS treatment significantly enhanced the
      blunted renal sympathetic nerve activity, blood pressure, and heart rate
      responses to NO synthase inhibitor N(G)-monomethyl-L-arginine in the rats with
      CHF compared with CHF-adenovirus vectors encoding beta-galactosidase group.
      AdnNOS significantly decreased the enhanced renal sympathetic nerve activity,
      blood pressure, and heart rate responses to N-methyl-D-aspartic acid in the rats
      with CHF (renal sympathetic nerve activity: 44+/-2% versus 79+/-6%; P<0.05)
      compared with CHF-adenovirus vectors encoding the beta-galactosidase group.
      AdnNOS transfection significantly reduced the increased NR(1) receptor mRNA
      expression (Delta35+/-5%) and protein levels (Delta24+/-4%) within the PVN in CHF
      rats. Furthermore, in neuronal NG-108 cells, NR(1) receptor protein expression
      decreased in a dose-dependent manner after AdnNOS transfection. According to our
      results, nNOS downregulation enhances glutamate transmission in the PVN by
      increasing NR(1) subunit expression. This mechanism may enhance renal sympathetic
      nerve activity in CHF rats.

PMID- 21968760
TI  - An unfortunate resurgence of human chorionic gonadotropin use for weight loss.

PMID- 21968761
TI  - Teasing and social rejection among obese children enrolling in family-based
      behavioural treatment: effects on psychological adjustment and academic
      competencies.
AB  - OBJECTIVES: The first objective was to determine the prevalence of psychological
      maladjustment (emotional and behavioural problems), low academic competencies and
      teasing/social rejection among obese Icelandic children enrolling in a family
      based behavioural treatment. A second objective was to explore the degree to
      which teasing/social rejection specifically contributes to children's
      psychological adjustment and academic competencies when controlling for other
      variables, including demographics, children's physical activity, parental
      depression and life-stress. METHODS: Participants were 84 obese children (mean
      body mass index-standard deviation score=3.11, age range=7.52-13.61 years).
      Height and weight, demographics and measures of children's psychological
      adjustment, academic competencies, teasing/social rejection and physical activity
      were collected from children, parents and teachers. Parental depression and life
      stress was self-reported. RESULTS: Over half the children exceeded cutoffs
      indicating concern on at least one measure of behavioural or emotional
      difficulties. Children endorsed significant levels of teasing/social rejection,
      with almost half acknowledging they were not popular with same-gender peers.
      Parent reports of peer problems were even higher, with over 90% of both boys and
      girls being rated by their parents as having significant peer difficulties.
      However, rates of low academic competencies as reported by teachers were not
      different from those of the general population. In regression analyses
      controlling for other variables, self-reported teasing/social rejection emerged
      as a significant contributor to explaining both child psychological adjustment
      and academic competencies. CONCLUSIONS: The results indicate that among obese
      children enrolled in family-based treatment, self-reported teasing/social
      rejection is quite high and it is associated with poorer psychological adjustment
      as well as lower academic competencies. Parent reports corroborate the presence
      of substantial peer difficulties, supporting the need to address peer relations
      with overweight children both in clinical practice and in public health
      interventions.

PMID- 21968762
TI  - Removal of organic debris with Er:YAG laser irradiation and microleakage of
      fissures sealants in vitro.
AB  - The current study was conducted to improve fissure sealing by pre-treatment with
      Er:YAG laser irradiation in order to remove organic debris. The surface
      morphology, surface roughness of fissure cavities, and the degree of microleakage
      after laser treatment were compared with those after bristle brush treatment in
      vitro. Sixty extracted human teeth were used in this study. The teeth were
      randomly divided into two groups of 30 each. Artificial fissures were prepared in
      all teeth into which artificial organic debris was placed. The debris in 30 teeth
      of one group was removed by means of Er:YAG laser system and the remaining 30
      teeth were cleaned using a bristle brush with prophylaxis paste. Surface
      morphology and surface roughness of were analyzed in ten samples from each group
      by color laser three-dimensional (3D) microscopy and by scanning electron
      microscopic examination. The remaining samples were then filled with sealant and
      subjected to a microleakage test under thermocycling. Statistical analysis was
      performed using the Mann-Whitney U test; a value of p < 0.05 was considered
      significant. Morphologically, most of the debris was removed by Er:YAG laser
      treatment, whereas some fissures were not cleaned by bristle brush. However,
      microleakage test of both laser and etched brush methods showed similar results.
      Laser technique might facilitate good adaptation of resin sealant to enamel,
      because of an increase in surface roughness and favorable surface
      characteristics.

PMID- 21968764
TI  - Retraction of "Genetic and biochemical analyses of sensor kinase A in Bacillus
      subtilis sporulation" by J.C. Nguele, P. Eswaramoorthy, M. Bhattacharya, E. Ngou
      Milama and M. Fujita. Genet. Mol. Res. 9 (1): 573-590 (2010).

PMID- 21968763
TI  - Effect of exogenous surfactant on phosphatidylinositol 3-kinase-Akt pathway and
      peroxisome proliferator activated receptor-gamma during endotoxin induced acute
      respiratory distress syndrome.
AB  - Lipopolysaccharide induced acute respiratory distress syndrome (ARDS) leads to an
      unacceptably high mortality. In this regard, the anti-inflammatory properties of
      surfactant may provide a therapeutic option. Phosphoinositide 3-kinase (PI3-K)
      and the downstream serine/threonine kinase Akt/protein kinase B have a central
      role in modulating neutrophil function, including respiratory burst, chemotaxis,
      and apoptosis. This study explores the mechanisms of surfactant dependent
      protection by regulating PPAR-gamma in a rat model of ARDS. Sprague-Dawley male
      rats were divided into four groups: buffer controls; rats challenged with LPS
      (055:B5 E. coli); challenged with LPS and treated with porcine surfactant; and
      challenged with LPS and treated with synthetic surfactant. Expression of PI3-K,
      Akt, GSK3-beta, and PPAR-gamma were studied by western immunoblot,
      immunofluorescence and by immunohistochemistry. In vivo endotoxin administration
      to rat resulted in activation of PI3-K and Akt in the lungs. The severity of
      endotoxemia-induced ALI was significantly diminished in rat with surfactant
      administration. Similar results were also seen in PPAR-gamma expression. These
      results show that PI3-K occupies a central position in regulating endotoxin
      induced ALI involving inflammatory responses. Surfactant treatment conferred
      protection in rat model dependent on PPAR-gamma and inhibition of PI3-K/Akt
      pathway.

PMID- 21968765
TI  - Gene expression in swine  granulosa cells and ovarian tissue during the estrous
      cycle.
AB  - The  components of the insulin-like growth factor (IGF) system appear to be
      involved  in regulation of ovarian follicular growth and atresia in the pig. We 
      investigated the expression pattern of mRNAs for IGF1 (IGF1), its  binding
      proteins (IGFBP1, IGFBP2, IGFBP3, and IGFBP5),  and epidermal growth factor in
      swine follicle cells and ovarian tissue  throughout the estrous cycle using the
      real-time quantitative PCR technique.  The results of gene expression were
      analyzed using linear regression with gene  expression as a dependent variable
      and days of estrous cycle as an independent  variable. Additionally, an analysis
      was made of the correlation of expression  levels with plasma concentration of
      follicle-stimulating hormone, luteinizing  hormone, estradiol-17beta, 
      progesterone, and prolactin. Expression of mRNA of all of these genes was 
      detected in granulosa cells and ovarian tissue. IGFBP3 mRNA showed a  quadratic
      expression pattern (P <= 0.001) and was significantly and positively  correlated
      with progesterone (r = 0.81; P <= 0.01) but negatively correlated  with prolactin
      (r = -0.596; P <= 0.05). Expression of the other genes was  unaffected by the
      stage of the estrous cycle. Real-time quantitative PCR  effectively detected all
      transcripts, including the very low levels of IGFBP1 transcripts, and could be
      used for studies of follicle dynamics.

PMID- 21968766
TI  - Combining ability of tropical maize lines for seed  quality and agronomic traits.
AB  - Studies of genetic effects of early selection of maize  based on seed quality
      traits are rare, especially those that use materials from  different heterotic
      groups. These studies are also useful in tropical  environments and for the
      advancement of sustainable agriculture with cropping  during seasons not commonly
      used for cultivation. We estimated, through diallel  crosses, the predominant
      genetic effects on the expression of agronomic traits  and seed quality and on
      the general combining ability of nine maize lines from commercial  hybrids and
      the specific combining ability of hybrid combinations among them.  In the
      evaluation of seed quality, seven tests were used: first count and final  count
      of seed germination, seedling vigor classification, cold tolerance,  seedling
      emergence rate in a sand seedbed, speed of emergence in a sand  seedbed, and
      speed of emergence index. Plant height, first ear height and grain  yield were
      the estimated agronomic traits. In the diallel analysis, method 3  (model I)
      proposed by Griffing was used. There was a greater significance of  non-additive
      genetic effects in the genetic control of seed quality of the  various lines. The
      Flash, Dekalb 350 and P 30F80 lines combined high seed  quality and high grain
      yield. For growth during the normal planting season, the  combinations CD 3121-1
      x P 30F80, Speed x CD 3121-2, Dow 8330 x AG 8080 and  Dekalb 350 x CD 3121-2 were
      the most promising for both seed quality and  agronomic traits.

PMID- 21968767
TI  - Rhythmogram-based analysis for continuous electrographic data of the human brain.
AB  - Ecologically relevant stimuli are rarely used in scientific studies because they
      are difficult to control. Instead, researchers employ simple stimuli with sharp
      boundaries (in space and time). Here, we explore how the rhythmogram can be used
      to provide much needed rigorous control of natural continuous stimuli like music
      and speech. The analysis correlates important features in the time course of
      stimuli with corresponding features in brain activations elicited by the same
      stimuli. Correlating the identified regularities of the stimulus time course with
      the features extracted from the activations of each voxel of a tomographic
      analysis of brain activity provides a powerful view of how different brain
      regions are influenced by the stimulus at different times and over different
      (user-selected) timescales. The application of the analysis to tomographic
      solutions extracted from magnetoencephalographic data recorded while subjects
      listen to music reveals a surprising and aesthetically pleasing aspect of brain
      function: an area believed to be specialized for visual processing is recruited
      to analyze the music after the acoustic signal is transformed to a feature map.
      The methodology is ideal for exploring processing of complex stimuli, e.g.,
      linguistic structure and meaning and how it fails, for example, in developmental
      dyslexia.

PMID- 21968768
TI  - Heat waves and cause-specific mortality at all ages.
AB  - BACKGROUND: Mortality has been shown to increase with extremely hot ambient
      temperatures. Details on the specific cause of mortality can be useful for
      improving preventive policies. Infants are often identified as a population that
      is vulnerable to extreme heat conditions; however, information on heat and infant
      mortality is scarce, with no studies reporting on cause-specific mortality.
      METHODS: The study includes all deaths in the Catalonia region of Spain during
      the warm seasons of 1983-2006 (503,389 deaths). We used the case-crossover design
      to evaluate the association between the occurrence of extremely hot days (days
      with maximum temperature above the 95th percentile) and mortality. Total
      mortality and infant mortality were stratified into 66 and 8 causes of death,
      respectively. RESULTS: Three consecutive hot days increased total daily mortality
      by 19%. We calculated that 1.6% of all deaths were attributable to heat. About
      40% of attributable deaths did not occur during heat-wave periods. The causes of
      death that were increased included cardiovascular and respiratory diseases,
      mental and nervous system disorders, infectious and digestive system diseases,
      diabetes, and some external causes such as suicide. In infants, the effect of
      heat was observed on the same day and was detected only for conditions
      originating in the perinatal period (relative risk = 1.53 [95% confidence
      interval = 1.16-2.02]). Within the perinatal causes, cardiovascular, respiratory,
      digestive system, and hemorrhagic and hematologic disorders were the causes of
      death with stronger effects. CONCLUSIONS: Heat contributes to an increase in
      mortality from several causes. In infants, the first week of life is the most
      critical window of vulnerability.

PMID- 21968769
TI  - Hand, foot, and mouth disease in China: patterns of spread and transmissibility.
AB  - BACKGROUND: There were large outbreaks of hand, foot, and mouth disease in both
      2008 and 2009 in China. METHODS: Using the national surveillance data since 2 May
      2008, we summarized the epidemiologic characteristics of the recent outbreaks.
      Using a susceptible-infectious-recovered transmission model, we evaluated the
      transmissibility of the disease and potential risk factors. RESULTS: Children
      ages 1.0 to 2.9 years were the most susceptible to hand, foot, and mouth disease
      (odds ratios [OR] >2.3 as compared with other age-groups). Infant cases had the
      highest incidences of severe disease (ORs >1.4) and death (ORs >2.4), as well as
      the longest delay from symptom onset to diagnosis (2.3 days). Boys were more
      susceptible than girls (OR = 1.56 [95% confidence interval = 1.56-1.57]). A 1-day
      delay in diagnosis was associated with increases in the odds of severe disease by
      40% (39%-42%) and in the odds of death by 54% (44%-65%). Compared with Coxsackie
      A16, enterovirus 71 is more strongly associated with severe disease (OR = 16 [13
      18]) and death (OR = 40 [13-127]). The estimated local effective reproductive
      numbers among prefectures ranged from 1.4 to 1.6 (median = 1.4) in spring and
      stayed below 1.2 in other seasons. A higher risk of transmission was associated
      with temperatures in the range of 70 degrees  F to 80 degrees F, higher relative
      humidity, higher [corrected] wind speed, more precipitation, greater population
      density, and [corrected] periods during which schools were open. CONCLUSION:
      Hand, foot, and mouth disease is a moderately transmittable infectious disease,
      mainly among preschool children. Enterovirus 71 was responsible for most severe
      cases and fatalities. Mixing of asymptomatically infected children in schools
      might have contributed to spread the of infection. Timely diagnosis may be
      [corrected] key to reducing the high mortality rate in infants.

PMID- 21968770
TI  - Joint modeling, covariate adjustment, and interaction: contrasting notions in
      risk prediction models and risk prediction performance.
AB  - Epidemiologic methods are well established for investigating the association of a
      predictor of interest and disease status in the presence of covariates also
      associated with disease. There is less consensus on how to handle covariates when
      the goal is to evaluate the increment in prediction performance gained by a new
      marker when a set of predictors already exists. We distinguish between adjusting
      for covariates and joint modeling of disease risk in this context. We show that
      adjustment and joint modeling are distinct concepts, and we describe the specific
      conditions where they are the same. We also discuss the concept of interaction
      among variables and describe a notion of interaction that is relevant to
      prediction performance. We conclude with a discussion of the most appropriate
      methods for evaluating new biomarkers in the presence of existing predictors.

PMID- 21968771
TI  - Averaged or stratified measures of risk profile discrimination: horses for
      courses.

PMID- 21968772
TI  - A method to detect residual confounding in spatial and other observational
      studies.
AB  - BACKGROUND: Residual confounding is challenging to detect. Recently, we described
      a method for detecting confounding and justified it primarily for time-series
      studies. The method depends on an indicator with 2 key characteristics: (1) it is
      conditionally independent (given measured exposures and covariates) of the
      outcome, in the absence of confounding, misspecification, and measurement errors;
      and (2) like the exposure, it is associated with confounders, possibly
      unmeasured. We proposed using future exposure levels as the indicator to detect
      residual confounding. This choice seems natural for time-series studies because
      future exposure cannot have caused the event, yet they could be spuriously
      related to it. A related question addressed here is whether an analogous
      indicator can be used to identify residual confounding in a study based on
      spatial, rather than temporal, contrasts. METHODS: Using directed acyclic graphs,
      we show that future air pollution levels may have the characteristics appropriate
      for an indicator of residual confounding in spatial studies of environmental
      exposures. We empirically evaluate performance for spatial studies using
      simulations. RESULTS: In simulations based on a spatial study of ambient air
      pollution levels and birth weight in Atlanta, and using ambient air pollution 1
      year after conception as the indicator, we were able to detect residual
      confounding. The discriminatory ability approached 100% for some factors
      intentionally omitted from the model, but was very weak for others. CONCLUSION:
      The simulations illustrate that an indicator based on future exposures can have
      excellent ability to detect residual confounding in spatial studies, although
      performance varied by situation.

PMID- 21968775
TI  - Exploratory quantile regression with many covariates: an application to adverse
      birth outcomes.
AB  - Covariates may affect continuous responses differently at various points of the
      response distribution. For example, some exposure might have minimal impact on
      conditional means, whereas it might lower conditional 10th percentiles sharply.
      Such differential effects can be important to detect. In studies of the
      determinants of birth weight, for instance, it is critical to identify exposures
      like the one above, since low birth weight is a risk factor for later health
      problems. Effects of covariates on the tails of distributions can be obscured by
      models (such as linear regression) that estimate conditional means; however,
      effects on tails can be detected by quantile regression. We present 2 approaches
      for exploring high-dimensional predictor spaces to identify important predictors
      for quantile regression. These are based on the lasso and elastic net penalties.
      We apply the approaches to a prospective cohort study of adverse birth outcomes
      that includes a wide array of demographic, medical, psychosocial, and
      environmental variables. Although tobacco exposure is known to be associated with
      lower birth weights, the analysis suggests an interesting interaction effect not
      previously reported: tobacco exposure depresses the 20th and 30th percentiles of
      birth weight more strongly when mothers have high levels of lead in their blood
      compared with those who have low blood lead levels.

PMID- 21968773
TI  - Dioxin and polychlorinated biphenyl concentrations in mother's serum and the
      timing of pubertal onset in sons.
AB  - BACKGROUND: Animal studies have demonstrated that timing of pubertal onset can be
      altered by prenatal exposure to dioxins or polychlorinated biphenyls (PCBs), but
      studies of human populations have been quite limited. METHODS: We assessed the
      association between maternal serum concentrations of dioxins and PCBs and the
      sons' age of pubertal onset in a prospective cohort of 489 mother-son pairs from
      Chapaevsk, Russia, a town contaminated with these chemicals during past
      industrial activity. The boys were recruited at ages 8 to 9 years, and 4 years of
      annual follow-up data were included in the analysis. Serum samples were collected
      at enrollment from both mothers and sons for measurement of dioxin and PCB
      concentrations using high-resolution mass spectrometry. The sons' pubertal onset-
      defined as pubertal stage 2 or higher for genitalia (G) or pubic hair (P), or
      testicular volume >3 mL--was assessed annually by the same physician. RESULTS: In
      multivariate Cox models, elevated maternal serum PCBs were associated with
      earlier pubertal onset defined by stage G2 or higher (4th quartile hazard ratio =
      1.7 [95% confidence interval = 1.1- 2.5]), but not for stage P2 or higher or for
      testicular volume >3 mL. Maternal serum concentrations of dioxin toxic
      equivalents were not consistently associated with the sons' pubertal onset,
      although a dose-related delay in pubertal onset (only for G2 or higher) was seen
      among boys who breast-fed for 6 months or more. CONCLUSIONS: Maternal PCB serum
      concentrations measured 8 or 9 years after sons' births--which may reflect sons'
      prenatal and early-life exposures--were associated with acceleration in some, but
      not all, measures of pubertal onset.

PMID- 21968776
TI  - A conversation with Leonard Syme. Interview by W. Thomas Boyce.

PMID- 21968774
TI  - Incidence of traumatic brain injury across the full disease spectrum: a
      population-based medical record review study.
AB  - BACKGROUND: Extremely few objective estimates of traumatic brain injury incidence
      include all ages, both sexes, all injury mechanisms, and the full spectrum from
      very mild to fatal events. METHODS: We used unique Rochester Epidemiology Project
      medical records-linkage resources, including highly sensitive and specific
      diagnostic coding, to identify all Olmsted County, MN, residents with diagnoses
      suggestive of traumatic brain injury regardless of age, setting, insurance, or
      injury mechanism. Provider-linked medical records for a 16% random sample were
      reviewed for confirmation as definite, probable, possible (symptomatic), or no
      traumatic brain injury. We estimated incidence per 100,000 person-years for 1987
      2000 and compared these record-review rates with rates obtained using Centers for
      Disease Control and Prevention (CDC) data-systems approach. For the latter, we
      identified all Olmsted County residents with any CDC-specified diagnosis codes
      recorded on hospital/emergency department administrative claims or death
      certificates during 1987-2000. RESULTS: Of sampled individuals, 1257 met record
      review criteria for incident traumatic brain injury; 56% were ages 16-64 years,
      56% were male, and 53% were symptomatic. Mechanism, sex, and diagnostic certainty
      differed by age. The incidence rate per 100,000 person-years was 558 (95%
      confidence interval = 528-590) versus 341 (331-350) using the CDC data-system
      approach. The CDC approach captured only 40% of record-review cases. Seventy-four
      percent of missing cases presented to the hospital/emergency department; none had
      CDC-specified codes assigned on hospital/emergency department administrative
      claims or death certificates; and 66% were symptomatic. CONCLUSIONS: Capture of
      symptomatic traumatic brain injuries requires a wider range of diagnosis codes,
      plus sampling strategies to avoid high rates of false-positive events.

PMID- 21968777
TI  - William Gorgas: yellow fever meets its nemesis.

PMID- 21968778
TI  - Sample size and power calculations for case-only interaction studies.

PMID- 21968779
TI  - Splines for trend analysis and continuous confounder control.

PMID- 21968780
TI  - Online questionnaires for outbreak investigations.

PMID- 21968781
TI  - "Suicide-related events in patients treated with antiepileptic drugs": not an
      example of time-window bias.

PMID- 21968782
TI  - Hormonal contraception and HIV risk: evaluating marginal-structural-model
      assumptions.

PMID- 21968784
TI  - Gestational diabetes among immigrant women.

PMID- 21968783
TI  - Danish sperm counts (cont'd.).

PMID- 21968785
TI  - Evidence for a shared mechanism used in multiple-object tracking and subitizing.
AB  - It has been proposed that the mechanism that supports the ability to keep track
      of multiple moving objects also supports subitizing--the ability to quickly and
      accurately enumerate a small set of objects. To test this hypothesis, we
      investigated the effects on subitizing when human observers were required to
      perform a multiple object tracking task and an enumeration task simultaneously.
      In three experiments, participants (Exp. 1, N = 24; Exp. 2, N = 11; Exp. 3, N =
      37) enumerated sets of zero to nine squares that were flashed while they tracked
      zero, two, or four moving discs. The results indicated that the number of items
      participants could subitize decreased by one for each item they tracked. No such
      pattern was seen when the enumeration task was paired with an equally difficult,
      but nonvisual, working memory task. These results suggest that a shared visual
      mechanism supports multiple object tracking and subitizing.

PMID- 21968787
TI  - Breakthrough in concentration quenching threshold of upconversion luminescence
      via spatial separation of the emitter doping area for bio-applications.
AB  - The concentration quenching threshold of upconversion luminescence was broken
      through for the first time via a designed strategy: spatial separation of the
      emitter doping area.

PMID- 21968786
TI  - Update on toxic myopathies.
AB  - The toxic myopathies are a clinically and pathologically diverse group of
      disorders that can be caused by a variety of therapeutic agents used in clinical
      practice, as well as various venoms and other biological toxins. The most
      important iatrogenic causes are the statin and fibrate cholesterol-lowering
      agents that can cause a severe necrotizing myopathy and acute rhabdomyolysis and
      myoglobinuria. The current update focuses on the mechanisms of statin myotoxicity
      and the importance of genetic predisposing factors for statin myopathy, as well
      as the recently described form of necrotizing autoimmune myopathy, which is
      associated with antibodies to the 3-hydroxy-3-methylglutaryl-coenzyme A reductase
      enzyme and is responsive to aggressive immunotherapy. Mitochondrial myopathies
      associated with antiretroviral agents and the pyrimidine nucleoside analogue
      clevudine, and recent reports of myopathies caused by ingestion of red yeast rice
      and toxic species of mushrooms are also discussed.

PMID- 21968788
TI  - Intraclonal complexity in chronic lymphocytic leukemia: fractions enriched in
      recently born/divided and older/quiescent cells.
AB  - The failure of chemotherapeutic regimens to eradicate cancers often results from
      the outgrowth of minor subclones with more dangerous genomic abnormalities or
      with self-renewing capacity. To explore such intratumor complexities in B-cell
      chronic lymphocytic leukemia (CLL), we measured B-cell kinetics in vivo by
      quantifying deuterium ((2)H)-labeled cells as an indicator of a cell that had
      divided. Separating CLL clones on the basis of reciprocal densities of chemokine
      (C-X-C motif) receptor 4 (CXCR4) and cluster designation 5 (CD5) revealed that
      the CXCR4(dim)CD5(bright) (proliferative) fraction contained more (2)H-labeled
      DNA and hence divided cells than the CXCR4(bright)CD5(dim) (resting) fraction.
      This enrichment was confirmed by the relative expression of two cell cycle
      associated molecules in the same fractions, Ki-67 and minichromosome maintenance
      protein 6 (MCM6). Comparisons of global gene expression between the
      CXCR4(dim)CD5(bright) and CXCR4(bright)CD5(dim) fractions indicated higher levels
      of pro-proliferation and antiapoptotic genes and genes involved in oxidative
      injury in the proliferative fraction. An extended immunophenotype was also
      defined, providing a wider range of surface molecules characteristic of each
      fraction. These intraclonal analyses suggest a model of CLL cell biology in which
      the leukemic clone contains a spectrum of cells from the proliferative fraction,
      enriched in recently divided robust cells that are lymphoid tissue emigrants, to
      the resting fraction enriched in older, less vital cells that need to immigrate
      to lymphoid tissue or die. The model also suggests several targets preferentially
      expressed in the two populations amenable for therapeutic attack. Finally, the
      study lays the groundwork for future analyses that might provide a more robust
      understanding of the development and clonal evolution of this currently incurable
      disease.

PMID- 21968789
TI  - Partial versus productive immunoglobulin heavy locus rearrangements in chronic
      lymphocytic leukemia: implications for B-cell receptor stereotypy.
AB  - The frequent occurrence of stereotyped heavy complementarity-determining region 3
      (VH CDR3) sequences among unrelated cases with chronic lymphocytic leukemia (CLL)
      is widely taken as evidence for antigen selection. Stereotyped VH CDR3 sequences
      are often defined by the selective association of certain immunoglobulin heavy
      diversity (IGHD) genes in specific reading frames with certain immunoglobulin
      heavy joining (IGHJ ) genes. To gain insight into the mechanisms underlying VH
      CDR3 restrictions and also determine the developmental stage when restrictions in
      VH CDR3 are imposed, we analyzed partial IGHD-IGHJ rearrangements (D-J) in 829
      CLL cases and compared the productively rearranged D-J joints (that is, in-frame
      junctions without junctional stop codons) to (a) the productive immunoglobulin
      heavy variable (IGHV )-IGHD-IGHJ rearrangements (V-D-J) from the same cases and
      (b) 174 D-J rearrangements from 160 precursor B-cell acute lymphoblastic leukemia
      cases (pre-B acute lymphoblastic leukemia [ALL]). Partial D-J rearrangements were
      detected in 272/829 CLL cases (32.8%). Sequence analysis was feasible in 238 of
      272 D-J rearrangements; 198 of 238 (83.2%) were productively rearranged. The D-J
      joints in CLL did not differ significantly from those in pre-B ALL, except for
      higher frequency of the IGHD7-27 and IGHJ6 genes in the latter. Among CLL
      carrying productively rearranged D-J, comparison of the IGHD gene repertoire in
      productive V-D-J versus D-J revealed the following: (a) overuse of IGHD reading
      frames encoding hydrophilic peptides among V-D-J and (b) selection of the IGHD3-3
      and IGHD6-19 genes in V-D-J junctions. These results document that the IGHD and
      IGHJ gene biases in the CLL expressed VH CDR3 repertoire are not stochastic but
      are directed by selection operating at the immunoglobulin protein level.

PMID- 21968790
TI  - Unraveling divergent gene expression profiles in bicuspid and tricuspid aortic
      valve patients with thoracic aortic dilatation: the ASAP study.
AB  - Thoracic aortic aneurysm (TAA) is a common complication in patients with a
      bicuspid aortic valve (BAV), the most frequent congenital heart disorder. For
      unknown reasons TAA occurs at a younger age, with a higher frequency in BAV
      patients than in patients with a tricuspid aortic valve (TAV), resulting in an
      increased risk for aortic dissection and rupture. To investigate the increased
      TAA incidence in BAV patients, we obtained tissue biopsy samples from nondilated
      and dilated aortas of 131 BAV and TAV patients. Global gene expression profiles
      were analyzed from controls and from aortic intima-media and adventitia of
      patients (in total 345 samples). Of the genes found to be differentially
      expressed with dilation, only a few (<4%) were differentially expressed in both
      BAV and TAV patients. With the use of gene set enrichment analysis, the cell
      adhesion and extracellular region gene ontology sets were identified as common
      features of TAA in both BAV and TAV patients. Immune response genes were observed
      to be particularly overexpressed in the aortic media of dilated TAV samples. The
      divergent gene expression profiles indicate that there are fundamental
      differences in TAA etiology in BAV and TAV patients. Immune response activation
      solely in the aortic media of TAV patients suggests that inflammation is involved
      in TAA formation in TAV but not in BAV patients. Conversely, genes were
      identified that were only differentially expressed with dilation in BAV patients.
      The result has bearing on future clinical studies in which separate analysis of
      BAV and TAV patients is recommended.

PMID- 21968792
TI  - Predictor-based compensation for electromechanical delay during neuromuscular
      electrical stimulation.
AB  - Electromechanical delay (EMD) is a biological artifact that arises due to a time
      lag between electrical excitation and tension development in a muscle. EMD is
      known to cause degraded performance and instability during neuromuscular
      electrical stimulation (NMES). Compensating for such input delay is complicated
      by the unknown nonlinear muscle force-length and muscle force-velocity
      relationships. This paper provides control development and a mathematical
      stability analysis of a NMES controller with a predictive term that actively
      accounts for EMD. The results are obtained through the development of a novel
      predictor-type method to address the delay in the voltage input to the muscle.
      Lyapunov-Krasovskii functionals are used within a Lyapunov-based stability
      analysis to prove semi-global uniformly ultimately bounded tracking. Experiments
      on able-bodied volunteers illustrate the performance and robustness of the
      developed controller during a leg extension trajectory following task.

PMID- 21968791
TI  - Preliminary evaluation of a powered lower limb orthosis to aid walking in
      paraplegic individuals.
AB  - This paper describes a powered lower-limb orthosis that is intended to provide
      gait assistance to spinal cord injured (SCI) individuals by providing assistive
      torques at both hip and knee joints. The orthosis has a mass of 12 kg and is
      capable of providing maximum joint torques of 40 Nm with hip and knee joint
      ranges of motion from 105 degrees  flexion to 30 degrees  extension and 105
      degrees  flexion to 10 degrees  hyperextension, respectively. A custom
      distributed embedded system controls the orthosis with power being provided by a
      lithium polymer battery which provides power for one hour of continuous walking.
      In order to demonstrate the ability of the orthosis to assist walking, the
      orthosis was experimentally implemented on a paraplegic subject with a T10
      complete injury. Data collected during walking indicates a high degree of step-to
      step repeatability of hip and knee trajectories (as enforced by the orthosis) and
      an average walking speed of 0.8 km/hr. The electrical power required at each hip
      and knee joint during gait was approximately 25 and 27 W, respectively,
      contributing to the 117 W overall electrical power required by the device during
      walking. A video of walking corresponding to the aforementioned data is included
      in the supplemental material.

PMID- 21968793
TI  - Asymmetric versus symmetric pulses for cortical microstimulation.
AB  - Intracortical microstimulation (ICMS), which has shown promise in the visual,
      auditory and somatosensory systems as a platform for sensory prostheses,
      typically relies on charged balanced, symmetric, biphasic stimulation. However,
      neural stimulation models as well as experiments conducted in cochlear implant
      users have suggested that charge balanced asymmetric pulses could generate lower
      detection thresholds for stimulation in terms of charge per phase. For this
      study, rats were chronically implanted with microelectrode arrays unilaterally in
      their right auditory cortex and then trained to detect ICMS delivered through a
      single electrode site in order to determine their behavioral threshold. This
      model was used in two experiments. The first experiment addressed the effect of
      lead phase direction, asymmetry, and phase duration on detection threshold. The
      second experiment fixed the cathode phase duration at 123 MUs and varied only the
      phase asymmetry and lead phase direction. Taken together, the results of these
      experiments suggest that, for ICMS, the primary determinant of threshold level is
      cathode phase duration, and that asymmetry provides no significant advantage when
      compared to symmetric, cathode leading pulses. However, symmetric anode leading
      pulses of less than or equal to 205 MUs per phase consistently showed higher
      thresholds when compared to all other pulses of equal cathode phase duration.

PMID- 21968794
TI  - The additive value of magnetic resonance imaging for bone edema in predicting
      rheumatoid arthritis development in early undifferentiated arthritis: comment on
      the article by Duer-Jensen et al.

PMID- 21968795
TI  - Fenofibrate-induced decrease of expression of CYP2C11 and CYP2C6 in rat.
AB  - This short communication is aimed to investigate whether the widely used
      hypolipidemic drug fenofibrate affects CYP2C11 and CYP2C6 in rats, both
      counterparts of human CYP2C9, known to metabolise many drugs including S-warfarin
      and largely used non-steroidal antiinflammatory drugs such as ibuprofen,
      diclofenac and others. The effects of fenofibrate on the expression of rat liver
      CYP2C11 and CYP2C6 were studied in both healthy Wistar rats and hereditary
      hypertriglyceridemic rats. Both strains of rats were fed on diet containing
      fenofibrate (0.1% w/w) for 20 days. Fenofibrate highly significantly suppressed
      the expression of mRNA of CYP2C11 and less that of CYP2C6 in liver microsomes of
      both rat strains; this effect was associated with a corresponding decrease in
      protein levels. The results indicate that the combination of fenofibrate with
      drugs metabolised by CYP2C9 in humans should be taken with caution as it may
      lead, for example, to the potentiation of warfarin effects. This type of drug
      interaction has been observed previously and the results presented here could
      contribute to the explanation of their mechanism.

PMID- 21968796
TI  - Evaluation of the Nitrite Test in Screening for Urinary Tract Infection in
      Febrile Children with Sickle Cell Anaemia in Maiduguri- Nigeria.
AB  - BACKGROUND: Urinary tract infection is a significant cause of morbidity in
      children with sickle cell anaemia (SCA). Individuals with SCA have increased risk
      of urinary tract infection (UTI). Facilities for urine culture may not be
      available in most rural and even some urban areas in most developing countries
      like Nigeria. It will therefore be useful to have a simple means of screening
      such children for UTI with the intent of prompt treatment.  MATERIALS AND
      METHODS: The study will evaluate the usefulness of the nitrite test in detecting
      UTI in febrile SCA children. This study was carried out in the Department of
      Paediatrics University of Maiduguri Teaching Hospital and State Specialist
      Hospital Maiduguri.  RESULTS: The study consisted of 250 children aged 6 months
      to 15 years with SCA presenting with fever (temperature >= 37. 5 degrees C).
      Midstream urine specimen was collected from older children and suprapubic bladder
      aspiration of urine specimen was collected from infants. Samples were subjected
      to nitrite test, culture and sensitivity. There was significant bacteriuria in 65
      (26+) children with SCA. A positive test for nitrite was obtained in 43 of the 65
      (66.2+) children. The nitrite test has a specificity of 93.5+ in detecting
      bacteriuria, a sensitivity of 66.2+, a positive predictive value of 78.2+ and a
      negative predictive value of 93.5+. A positive nitrite test was significantly
      associated with bacteriuria, while a negative test was also significantly
      associated with an absence of bacteriuria.  CONCLUSIONS: From this study, the
      nitrite test is useful as a screening test for UTI in SCA children. However in
      sick children with SCA, microscopy, culture and sensitivity should still be done
      in spite of a negative nitrite test.

PMID- 21968798
TI  - A highly Lewis acidic triarylborane bearing peripheral o-carborane cages.
AB  - A triarylborane (2) bearing three o-carborane cages at peripheral positions on
      the aryl groups was prepared and its crystal structure was determined from X-ray
      diffraction study. Treatment of 2 with KF in the presence of 18-crown-6 led to
      the potassium salt, [2F](-). A UV-vis titration experiment carried out in
      THF/H(2)O (9/1 v/v) showed that 2 binds fluoride ions with a binding constant (K)
      of 4.8 * 10(4) M(-1), which is an order-of-magnitude greater than K for the mono
      carborane substituted triarylborane. The enhanced fluoride ion affinity of 2
      indicates an apparent additive effect of multiple carborane substitutions on the
      Lewis acidity enhancement of the triarylborane. The highly Lewis acidic nature of
      2 was further utilized in evaluating the fluoride ion affinity of
      tris(pentafluorophenyl)borane (B(C(6)F(5))(3)). A fluoride exchange reaction
      between [2F](-) and B(C(6)F(5))(3) resulted in 15 times higher fluorophilicity
      for B(C(6)F(5))(3) than for 2. The lower Lewis acidity of 2 compared with
      B(C(6)F(5))(3) was confirmed from its greater cathodic reduction potential.

PMID- 21968797
TI  - Clinical outcome after microfracture of the knee: a meta-analysis of before/after
      data of controlled studies.
AB  - PURPOSE: The aims of this study were to systematically review the medical
      literature, in order to find controlled studies about microfracture in the
      treatment of patients with full-thickness cartilage lesions of the knee, to
      statistically combine these studies in order to determine a best estimate of the
      average treatment effect, and to gather information to detect cartilage-specific
      and patient-specific factors that might have an influence on the clinical
      outcome. METHODS: We searched four electronic databases for controlled clinical
      trials or controlled prospective observational studies. We pooled before/after
      data of study arms using the term microfracture. RESULTS: We calculated an
      overall best estimate of 1.106, with [0.566; 1.646] as 95% confidence interval of
      the mean standardized treatment effect for a representative patient population.
      CONCLUSIONS: Our meta-analysis revealed a clinically relevant improvement of the
      postoperative clinical status as compared to the preoperative status. An increase
      of 22 overall KOOS points may provide a rough estimate for the mean expected
      treatment effect achieved by microfracturing.

PMID- 21968799
TI  - The training-induced changes on automatism, conduction and myocardial
      refractoriness are not mediated by parasympathetic postganglionic neurons
      activity.
AB  - The purpose of this study is to test the role that parasympathetic postganglionic
      neurons could play on the adaptive electrophysiological changes produced by
      physical training on intrinsic myocardial automatism, conduction and
      refractoriness. Trained rabbits were submitted to a physical training protocol on
      treadmill during 6 weeks. The electrophysiological study was performed in an
      isolated heart preparation. The investigated myocardial properties were: (a)
      sinus automatism, (b) atrioventricular and ventriculoatrial conduction, (c)
      atrial, conduction system and ventricular refractoriness. The parameters to study
      the refractoriness were obtained by means of extrastimulus test at four different
      pacing cycle lengths (10% shorter than spontaneous sinus cycle length, 250, 200
      and 150 ms) and (d) mean dominant frequency (DF) of the induced ventricular
      fibrillation (VF), using a spectral method. The electrophysiological protocol was
      performed before and during continuous atropine administration (1 MUM), in order
      to block cholinergic receptors. Cholinergic receptor blockade did not modify
      either the increase in sinus cycle length, atrioventricular conduction and
      refractoriness (left ventricular and atrioventricular conduction system
      functional refractory periods) or the decrease of DF of VF. These findings reveal
      that the myocardial electrophysiological modifications produced by physical
      training are not mediated by intrinsic cardiac parasympathetic activity.

PMID- 21968800
TI  - Class II phosphoinositide 3-kinase C2alpha: what we learned so far.
AB  - More than fifteen years after the first identification of a class II isoform of
      phosphoinositide 3-kinase (PI3K) in Drosophila melanogaster this subfamily
      remains the most enigmatic among all PI3Ks. What are the functions of these
      enzymes? What are their mechanisms of activation? Which downstream effectors are
      specifically regulated by these isoforms? Are class I and class II PI3Ks
      redundant or do they control different intracellular processes? And, more
      important, do class II PI3Ks have a role in human diseases? The recent increased
      interest on class II PI3Ks has started providing some answers to these questions
      but still a lot needs to be done to completely uncover the contribution of these
      enzymes to physiological processes and possibly to pathological conditions. Here
      we will summarise the recent findings on the alpha isoform of mammalian class II
      PI3Ks (PI3K-C2alpha ) and we will discuss the potential involvement of this
      enzyme in human diseases.

PMID- 21968802
TI  - The Launch of International Journal of Biochemistry and Molecular Biology.

PMID- 21968801
TI  - Amplifying and quantifying HIV-1 RNA in HIV infected individuals with viral loads
      below the limit of detection by standard clinical assays.
AB  - Amplifying viral genes and quantifying HIV-1 RNA in HIV-1 infected individuals
      with viral loads below the limit of detection by standard assays (below 50-75
      copies/ml) is necessary to gain insight to viral dynamics and virus host
      interactions in patients who naturally control the infection and those who are on
      combination antiretroviral therapy (cART).  Here we describe how to amplify viral
      genomes by single genome sequencing (the SGS protocol) (13, 19) and how to
      accurately quantify HIV-1 RNA in patients with low viral loads (the single-copy
      assay (SCA) protocol) (12, 20).  The single-copy assay is a real-time PCR assay
      with sensitivity depending on the volume of plasma being assayed. If a single
      virus genome is detected in 7 ml of plasma, then the RNA copy number is reported
      to be 0.3 copies/ml. The assay has an internal control testing for the efficiency
      of RNA extraction, and controls for possible amplification from DNA or
      contamination. Patient samples are measured in triplicate. The single-genome
      sequencing assay (SGS), now widely used and considered to be non-labor intensive
      (3, 7, 12, 14, 15),is a limiting dilution assay, in which endpoint diluted cDNA
      product is spread over a 96-well plate. According to a Poisson distribution, when
      less than 1/3 of the wells give product, there is an 80% chance of the PCR
      product being resultant of amplification from a single cDNA molecule. SGS has the
      advantage over cloning of not being subjected to resampling and not being biased
      by PCR-introduced recombination (19). However, the amplification success of SCA
      and SGS depend on primer design. Both assays were developed for HIV-1 subtype B,
      but can be adapted for other subtypes and other regions of the genome by changing
      primers, probes, and standards.

PMID- 21968803
TI  - Bioavailability, ecotoxicity, and geological characteristics of trace lead in
      sediments from two sites on Negro River, Uruguay, South America.
AB  - Bioassays of two sites along the Rio Negro in Uruguay indicate ecotoxicity, which
      could be attributable to trace concentrations of lead in river sediments. Monthly
      samples at two sites at Baygorria and Bonete locations were analyzed for both
      particle size and lead. Lead was determined by atomic spectrometry in river water
      and sediment and particle size by sieving and sedimentation. Data showed that
      Baygorria's sediments have greater percentage of clay than Bonete's (20.4 and
      5.8%, respectively). Lead was measurable in Baygorria's sediments, meanwhile in
      Bonete's, it was always below the detection limit. In water samples, lead was
      below detection limit at both sites. Bioassays using sub-lethal growth and
      survival test with Hyalella curvispina amphipod, screening with bioluminescent
      bacteria Photobacterium leiognathi, and acute toxicity bioassay with Pimephales
      promelas fish indicated toxicity at Baygorria, with much less effect at Bonete.
      Even though no lethal effects could be demonstrated, higher sub-lethal toxicity
      was found in samples from Baygorria site, showing a possible concentration of the
      contaminant in the clay fraction.

PMID- 21968804
TI  - Mobilization of arsenic and other trace elements of health concern in groundwater
      from the Sali River Basin, Tucuman Province, Argentina.
AB  - The Sali River Basin in north-west Argentina (7,000 km(2)) is composed of a
      sequence of Tertiary and Quaternary loess deposits, which have been substantially
      reworked by fluvial and aeolian processes. As with other areas of the Chaco
      Pampean Plain, groundwater in the basin suffers a range of chemical quality
      problems, including arsenic (concentrations in the range of 12.2-1,660 MUg L(
      1)), fluoride (50-8,740 MUg L(-1)), boron (34.0-9,550 MUg L(-1)), vanadium (30.7
      300 MUg L(-1)) and uranium (0.03-125 MUg L(-1)). Shallow groundwater (depths up
      to 15 m) has particularly high concentrations of these elements. Exceedances
      above WHO (2011) guideline values are 100% for As, 35% for B, 21% for U and 17%
      for F. Concentrations in deep (>200 m) and artesian groundwater in the basin are
      also often high, though less extreme than at shallow depths. The waters are
      oxidizing, with often high bicarbonate concentrations (50.0-1,260 mg L(-1)) and
      pH (6.28-9.24). The ultimate sources of these trace elements are the volcanic
      components of the loess deposits, although sorption reactions involving secondary
      Al and Fe oxides also regulate the distribution and mobility of trace elements in
      the aquifers. In addition, concentrations of chromium lie in range of 79.4-232
      MUg L(-1) in shallow groundwater, 129-250 MUg L(-1) in deep groundwater and 110
      218 MUg L(-1) in artesian groundwater. All exceed the WHO guideline value of 50
      MUg L(-1). Their origin is likely to be predominantly geogenic, present as
      chromate in the ambient oxic and alkaline aquifer conditions.

PMID- 21968805
TI  - Genetic and  epigenetic status of triple exotic consanguinity cotton
      introgression lines.
AB  - Introgression  lines are some of the most important germplasm for breeding
      applications and  other research conducted on cotton crops. The DNA methylation
      level among 10  introgression lines of cotton (Gossypium hirsutum) and three
      exotic  parental species (G. arboreum, G. thurberi and G. barbadense)  were
      assessed by methylation-sensitive amplified polymorphism (MSAP)  technology. The
      methylation level in the introgression lines ranged from 33.3  to 51.5%. However,
      the lines PD0111 and PD0113 had the lowest methylation level  (34.6 and 33.3%,
      respectively) due to demethylation of most non-coding  sequences. Amplified
      fragment length polymorphism (AFLP) was used to evaluate  the genetic
      polymorphism in the cotton introgression lines. A high degree of  polymorphism
      was observed in all introgression lines (mean 47.2%) based on AFLP  and MSAP
      analyses. This confirmed the effects of genetic improvement on cotton 
      introgression lines. The low methylation varieties, PD0111 and PD0113 
      (introgression lines), clustered outside of the introgression lines based on 
      MSAP data, which was incongruent with an AFLP-based dendrogram. This phenomenon 
      could be caused by environmental changes or introgression of exotic DNA 
      fragments.

PMID- 21968806
TI  - G501C polymorphism of the  oxidized LDL receptor gene is associated with
      albuminuria in Chinese essential  hypertension patients.
AB  - Albuminuria  is an independent predictor of renal and cardiovascular
      complications in  hypertensive subjects. We previously showed that lectin-like
      oxidized low  density lipoprotein receptor 1 (OLR-1) polymorphisms at G501C are
      associated  with susceptibility to essential hypertension and serum C-reactive
      protein  levels. We have now investigated a possible association between OLR-1 
      polymorphisms at G501C, genotyped by PCR-RFLP, and severity of albuminuria in 
      307 hypertensive Chinese subjects and 225 age- and sex-matched controls. Urine
      albumin  concentration /urine creatinine concentrations (ACR) were measured to
      evaluate  the severity of albuminuria. Hypertensive subjects had a significantly
      higher  frequency of the CC genotype and the C allele of the OLR-1 polymorphism
      than  controls; this was also true for . hypertensive subjects with
      macroalbuinuria  and microalbuminuria compared to those with normoalbuminuria.
      The mean ACR  levels and mean serum C-reactive protein levels in CC carriers were
      significantly higher than in GG and GC carriers. There was a significant, 
      positive correlation between serum hs-C-reactive protein levels and ACR levels. 
      We conclude that OLR-1 polymorphisms at G501C affect the severity of  albuminuria
      in essential hypertension patients.

PMID- 21968807
TI  - Proteomic  analysis of non-tumoral breast tissue.
AB  - Breast cancer is a complex and  heterogeneous disease. In spite of the advances
      made in recent decades, a  better understanding of the intrinsic mechanisms of
      this disease is crucial.  The development of new biomarkers is absolutely
      necessary to improve diagnosis  and prognosis. Research using the proteomic
      approach has generated interesting  results; however, the complexity of the
      mammary gland and of breast tumors  remains a major limitation to the development
      of new markers. An initial step  is to characterize non-tumoral human breast
      tissue. We present data from  classical proteomic analysis based on 2-D
      electrophoresis and peptide mass  fingerprinting identification, which were
      performed on six non-tumoral samples  from patients with invasive ductal breast
      carcinomas. Forty-four different  proteins from 70 spots were identified and
      classified according to their  biological function. Cytoskeleton and associated
      proteins represent the largest  class (30%) followed by the proteins with binding
      function (27%). Several of  the proteins have been described in breast tumors,
      such as vimentin,  endoplasmin, small heat shock beta-6, disulfide isomerase and
      some cell growth,  and proliferation regulators, suggesting the importance of
      including data on  the characterization of non-tumoral breast and to studies on
      differential  expression in cancer tissue.

PMID- 21968808
TI  - Prospective analysis of KRAS wild-type patients with metastatic colorectal cancer
      using cetuximab plus  FOLFIRI or FOLFOX4 treatment regimens.
AB  - Cetuximab,  a monoclonal antibody targeting epidermal growth factor receptor, has
      proven to  be efficient in the treatment of metastatic colorectal cancer. We made
      a  prospective study of the efficacy and toxicities of cetuximab-combination 
      first-line (FOLFOX4) versus second/third-line (FOLFIRI) chemotherapy in 98 KRAS
      wild-type patients who had metastatic colorectal cancer. Wild-type KRAS had  been
      identified by direct sequencing. Associations between clinical 
      response/progression-free survival/overall survival/toxicities and cetuximab
      combination  chemotherapy timing were evaluated. The overall response rate was 
      significantly higher for first-line treatment than for second/third-line 
      treatment (relative risk = 1.707, 95% confidence interval = 1.121-2.598). Both 
      progression-free survival and overall survival indicated significantly longer 
      survival of first-line treatment than second/third-line treatment patients.  This
      study is a validation of a molecular analysis of KRAS wild-type  status for the
      prediction of response to cetuximab-combination chemotherapy for  metastatic
      colorectal cancer patients; its predictive role was less prominent  in the
      second/third-line than in the first-line treatment patients.

PMID- 21968809
TI  - Antioxidant N-acetyl cysteine reverses cigarette smoke-induced myocardial
      infarction by inhibiting inflammation and oxidative stress in a rat model.
AB  - The contribution of chronic tobacco exposure in determining post-myocardial
      infarction (MI) left ventricular (LV) remodeling and possible therapeutic
      strategies has not been investigated systematically. In this small animal
      investigation, we demonstrate that chronic tobacco smoke exposure leading up to
      acute MI in rats is associated with greater histological extent of myocardial
      necrosis and consequent worse LV function. These findings are associated with
      increased transcriptomic expression of pro-inflammatory cytokines, tissue repair
      molecules and markers of oxidative stress in the myocardium. The results
      demonstrate that an N-acetyl cysteine (NAC) treatment significantly reduced
      tobacco-exposed induced infarct size and percent fractional shortening. A
      significantly increased LV end-systolic diameter was observed in tobacco-exposed
      sham compared to tobacco-naive sham (4.92+/-0.41 vs 3.45+/-0.33; P<0.05), and
      tobacco-exposed MI compared to tobacco-naive MI (8.24+/-0.3 vs 6.1+/-0.49;
      P<0.01) rats. Decreased intracardiac mRNA expression of the markers of
      inflammation, tissue repair and oxidative stress and circulating levels of pro
      inflammatory cytokines accompanied these positive effects of NAC. The treatment
      of tobacco-exposed MI rats with NAC resulted in significantly increased levels of
      intracardiac mRNA expression of antioxidants, including superoxide dismutase,
      thioredoxin and nuclear factor-E2-related factor 2, as well as circulating levels
      of glutathione (7+/-0.12 vs 10+/-0.18; P<=0.001), where the levels were almost
      identical to the tobacco-naive sham rats. These findings identify a novel post
      infarction therapy for amelioration of the adverse effects of tobacco exposure on
      the infracted myocardium and advocate the use of dietary supplement antioxidants
      for habitual smokers to prevent and reverse cardiovascular adverse effects in the
      absence of successful achievement of cessation of smoking.

PMID- 21968810
TI  - Roles of beta-catenin signaling in phenotypic expression and proliferation of
      articular cartilage superficial zone cells.
AB  - The superficial zone (SFZ) of articular cartilage has unique structural and
      biomechanical features, is thought to promote self-renewal of articular
      cartilage, and is thus important for joint long-term function, but the mechanisms
      regulating its properties remain unclear. Previous studies revealed that Wnt/beta
      catenin signaling is continuously active in SFZ, indicating that it may be
      essential for SFZ function. Thus, we examined whether Wnt/beta-catenin signaling
      regulates proliferation and phenotypic expression in SFZ cells. Using transgenic
      mice, we found that acute activation of Wnt/beta-catenin signaling increases SFZ
      thickness, Proteoglycan 4 (Prg4, also called lubricin) expression and the number
      of slow-cell cycle cells, whereas conditional ablation of beta-catenin causes the
      opposite. We developed a novel method to isolate SFZ cell-rich populations from
      the epiphyseal articular cartilage of neonatal mice, and found that the SFZ cells
      in culture exhibit a fibroblastic cytoarchitecture and higher Prg4 and Ets
      related gene (Erg) expression and lower aggrecan expression compared with
      chondrocyte cultures. Gene array analyses indicated that SFZ cells have distinct
      gene expression profiles compared with underlying articular chondrocytes.
      Treatment of Wnt3a strongly stimulated SFZ cell proliferation and maintained
      strong expression of Prg4 and Erg, whereas ablation of beta-catenin strongly
      impaired proliferation and phenotypic expression. When the cells were
      transplanted into athymic mice, they formed Prg4- and aggrecan-expressing
      cartilaginous masses attesting to their autonomous phenotypic capacity. Ablation
      of beta-catenin caused a rapid loss of Prg4 gene expression and strong increases
      in expression of aggrecan and collagen 10, the latter being a trait of
      hypertrophic chondrocytes. Together, the data reveal that Wnt/beta-catenin
      signaling is a key regulator of SFZ cell phenotype and proliferation, and may be
      as important for articular cartilage long-term function.

PMID- 21968811
TI  - Wnt activation downregulates olfactomedin-1 in Fallopian tubal epithelial cells:
      a microenvironment predisposed to tubal ectopic pregnancy.
AB  - Ectopic pregnancy (EP) occurs when the embryo fails to transit to the uterus and
      attach to the luminal epithelium of the Fallopian tube (FT). Tubal EP is a common
      gynecological emergency and more than 95% of EP occurs in the ampullary region of
      the FT. In humans, Wnt activation and downregulation of olfactomedin-1 (Olfm-1)
      occur in the receptive endometrium and coincided with embryo implantation in
      vivo. Whether similar molecular changes happen in the FT leading to EP remains
      unclear. We hypothesized that activation of Wnt signaling downregulates Olfm-1
      expression predisposes to EP. We investigated the spatiotemporal expression of
      Olfm-1 in FT from non-pregnant women and women with EP, and used a novel
      trophoblastic spheroid (embryo surrogate)-FT epithelial cell co-culture model
      (JAr and OE-E6/E7 cells) to study the role of Olfm-1 on spheroid attachment. Olfm
      1 mRNA expression in the ampullary region of non-pregnant FT was higher (P<0.05)
      in the follicular phase than in the luteal phase. Ampullary tubal Olfm-1
      expression was lower in FT from women with EP compared to normal controls at the
      luteal phase (histological scoring (H-SCORE)=1.3+/-0.2 vs 2.4+/-0.5; P<0.05).
      Treatment of OE-E6/E7 with recombinant Olfm-1 (0.2-5 MUg/ml) suppressed spheroid
      attachment to OE-E6/E7 cells, while activation of Wnt-signaling pathway by Wnt3a
      or LiCl reduced endogenous Olfm-1 expression and increased spheroid attachment.
      Conversely, suppression of Olfm-1 expression by RNAi increased spheroid
      attachment to OE-E6/E7 cells. Taken together, Wnt activation suppresses Olfm-1
      expression, and this may predispose a favorable microenvironment of the retained
      embryo in the FT, leading to EP in humans.

PMID- 21968812
TI  - The mitochondrial respiratory chain has a critical role in the antiviral process
      in Coxsackievirus B3-induced myocarditis.
AB  - Well-established differences in Coxsackievirus B3 (CVB3) elimination in resistant
      C57BL/6 and permissive A.SW/SnJ mice provide suitable models for studying the
      significance of the link between mitochondrial respiratory chain (RC),
      antioxidative stress components and mitochondrion-related apoptosis in the
      context of myocardial virus elimination. Distinct myocardial CVB3 titer in
      C57BL/6 (2.5 +/- 1.4 * 10(4) plaque-forming units (p.f.u.)/g tissue) and A.SW/SnJ
      mice (1.4 +/- 0.8 * 10(7) p.f.u./g) were associated with differences in the
      cardiac mitochondrial function 8 days post infection (p.i.). Infected C57BL/6
      mouse hearts disclosed increased complex I (CI) and CIII activity, but restricted
      CII and normal CIV activity of RC. Reduced expression of the antioxidative
      catalase was accompanied by elevated lipid peroxidation (LPO), indicating
      oxidative stress. Intrinsic apoptosis was activated demonstrated by elevated
      levels of Bax, Bcl-2, caspase 3 and DNA degradation. In contrast, all myocardial
      RC complex activities were restricted in CVB3-infected A.SW/SnJ mice. The
      antioxidative system provided sufficient protection against oxidative stress
      shown by an elevated catalase expression and unaltered LPO. Bax and Bcl-2 levels
      were unchanged in CVB3-infected A.SW/SnJ mice, while caspase 3 was moderately
      increased but no DNA degradation was detectable. Correlation analyses including
      data from the two mouse strains revealed that reduced CVB3 titer correlated with
      increased CI and CIII activity, oxidative stress as well as active apoptosis
      during acute myocarditis (MC). C57BL/6 mice completely eliminated CVB3 and
      inflammation and normalized all intracellular parameters, while A.SW/SnJ mice
      showed permanently restricted CI activity in chronic MC 90 days p.i., at which
      time the replicating virus was no longer detectable but immunological processes
      were still active. Consequently, the regulation of energy metabolism appears
      crucial for an effective virus elimination and may be of prognostic and
      therapeutic significance for patients with virus-induced MC.

PMID- 21968813
TI  - A novel origin for granulovacuolar degeneration in aging and Alzheimer's disease:
      parallels to stress granules.
AB  - The phosphorylated ribosomal protein S6 (pS6) is associated with the 40S
      ribosomal subunit in eukaryotes and is thought to have a role in RNA storage,
      degradation, and re-entry into translation. In this study, we found pS6 localized
      to granulovacuolar degeneration (GVD) within the pyramidal neurons.
      Immunohistochemical analysis found that nearly 20-fold more neurons contain pS6
      positive granules in Alzheimer's disease (AD) hippocampus compared with age
      matched controls. Further, pS6-positive granules were more common in neurons not
      containing neurofibrillary tangles (NFTs), were never associated with
      extracellular NFTs or in apoptotic neurons, and contained less RNA than
      neighboring pyramidal neurons not containing pS6-positive granules. In model
      systems, pS6 is a specific marker for stress granules, and another stress granule
      protein, p54/Rck, was also found to be a component of GVD in the current study.
      Stress granules are transient, intracellular, dense aggregations of proteins and
      RNAs that accumulate as a stress response, protecting cells from apoptosis and
      inappropriate transcriptional activity, often described as a form of 'molecular
      triage.' The RNA oxidation modification 8-hydroxyguanosine (8OHG) is strikingly
      increased in AD, yet this study reports that those neurons with pS6 granules
      display reduced RNA oxidation demonstrated by lower levels of 8OHG. Since chronic
      oxidative stress is central to AD pathogenesis, and RNA is a specific oxidative
      stress target and is intimately associated with stress granule biogenesis in
      model systems, we suggest that GVD in human brain parallel stress granules, and
      may in fact be more representative of early disease pathogenesis than
      traditionally believed. This proposed origin for GVD as a neuroprotective
      response, may represent a morphologic checkpoint between cell death and
      reversible cellular stress that proceeds in the absence of other inclusions.

PMID- 21968814
TI  - Comparison of transepidermal water loss and laser scanning microscopy
      measurements to assess their value in the characterization of cutaneous barrier
      defects.
AB  - The exact qualitative and quantitative analysis of wound healing processes is a
      decisive prerequisite for optimizing wound care and for therapy control.
      Transepidermal water loss (TEWL) measurements are considered to be the standard
      procedure for assessing the progress of epidermal wound healing. The damage to
      the stratum corneum correlates with an increased loss of water through the skin
      barrier. This method is highly susceptible to failure by environmental factors,
      in particular by temperature and moisture. This study was aimed at comparing TEWL
      measurements and in vivo laser scanning microscopy (LSM) for the characterization
      of the epidermal wound healing process. LSM is a high-resolution in vivo method
      permitting to analyze the kinetics and dynamics of wound healing at a cellular
      level. While the TEWL values for the individual volunteers showed a wide
      scattering, LSM permitted the wound healing process to be clearly characterized
      at the cellular level. However, a comparison between the two methods was very
      difficult, because the results provided by LSM were images and not numerical.
      Therefore, a scoring system was set up which evaluates the stages of wound
      healing. Thus, the healing process could be numerically described. This method is
      independent of any environmental factors. Providing morphologically qualitative
      and numerically quantitative analyses of the wound healing process and being far
      less vulnerable to failure, LSM is advantageous over TEWL.

PMID- 21968815
TI  - Quantitative computed tomography and computed tomography in children.
AB  - Quantitative computed tomography (QCT) methodologies have been instrumental in
      deepening our understanding of bone acquisition and strength during childhood.
      Important publications in the last year have drawn attention to the functional
      muscle-bone unit, showing that factors such as population ancestry, bone size,
      and muscle composition are additional dimensions of bone strength that affect
      muscle-bone relationships. The role of adiposity in pediatric bone health is
      complex and may vary by sex, puberty stage, and degree of obesity. Several new
      studies have demonstrated the association of peripheral QCT (pQCT) outcomes with
      fracture, although pQCT outcomes are not superior to dual-energy x-ray
      absorptiometry measures in this regard. New high-resolution pQCT studies document
      transient weakness in mid-puberty that coincides developmentally with the period
      of peak fracture incidence. These new studies will ultimately help us understand
      the development of sex differences in bone strength that emerge in adolescence.

PMID- 21968817
TI  - Comprehensive miRNome and in silico analyses identify the Wnt signaling pathway
      to be altered in the diabetic liver.
AB  - Aberrant microRNA expression patterns underlie the pathogenesis of diverse
      diseases, however in a disease as complex as diabetes where the liver exhibits
      deregulations of normal metabolic processes, the status and role of microRNAs are
      not yet completely understood. In a step towards unraveling this correlation, we
      assessed the global microRNA expression profiles in the control and diabetic
      (db/db) mice liver. These db/db mice were on a C57BLKS/J background and they
      exhibit diabetic phenotypes that are remarkably similar to those in humans.
      microRNA microarray profiling revealed 11 miRNAs to be up-regulated and 2 to be
      down-regulated in the db/db mice liver. Predicted targets of these differentially
      expressed microRNAs were retrieved from miRanda and TargetScan and the maximum
      number of commonly predicted targets mapped onto the Wnt signaling pathway that
      is otherwise conventionally associated with organogenesis and development.
      Towards validation of this prediction, we found that major components of the Wnt
      signaling pathway are inhibited in the db/db mice liver. A significant number of
      these down-regulated genes of the Wnt signaling pathway are predicted targets to
      the up-regulated miRNAs and specifically our results show that miR-34a and miR-22
      decreased the protein levels of their targets. Overexpression of miR-34a and miR
      22 and also inhibition of Wnt signaling using specific inhibitors led to
      increased lipid accumulation in HepG2 cells. Our data suggest that the Wnt
      signaling pathway could contribute towards the deregulated hepatic behavior in
      these animals and an altered hepatic miRNA signature could be playing a
      regulatory role herein.

PMID- 21968816
TI  - Rickets.
AB  - Rickets is disorder of a growing child arising from disorders that result in
      impaired apoptosis of hypertrophic cells and mineralization of the growth plate.
      Rickets due to nutritional causes remains an important global problem. The
      factors responsible for resurgence of rickets among dark-skinned infants living
      in developed countries include the following: residence in northern or southern
      latitudes, voluntary avoidance of exposure to solar ultraviolet B radiation,
      maternal vitamin D deficiency during pregnancy, and prolonged breastfeeding
      without provision of vitamin D supplements. Fibroblast growth factor 23 (FGF23),
      secreted by osteocytes, is an important regulator of serum phosphate and
      1,25(OH)(2)D(3) levels. Hypophosphatemic rickets resulting from increased
      synthesis or under-catabolism of FGF23 is reviewed.

PMID- 21968819
TI  - Determination of minimum effective height of transparent radiation face shielding
      for fluoroscopy.
AB  - During interventional procedures, the vast majority of scatter radiation
      originates from the patient and table and travels in all directions in straight
      lines. Because the operator's head is much higher than the patient and at an
      angle upward and to the side of the patient (not directly above), the scatter
      received by the operator's head is projected in an upward angle. Thus a face
      shield could potentially be lower than the object it is shielding, e.g., below
      the eyes. This principle may be used as an advantage to design the lowest shield
      that effectively protects the head while providing optimum vision, appearance,
      acoustics, low weight, and sense of openness. A flat acrylic plate shield, 0.5 mm
      Pb equivalence, was suspended vertically in front of a 451P dosimeter. A phantom
      patient created scatter in an interventional suite while the dosimeter was placed
      at the level of the crowns of different operators' heads. Many different
      configurations were tested to determine which ones would provide effective
      shielding. The results confirmed that the top of the shield may reside several
      centimeters below the vertical height of the dosimeter (operator's crown),
      allowing line of sight to monitor above the shield, and still provide effective
      shielding equivalent to when the dosimeter is positioned directly behind the
      center of the shield. The image receptor functioned as an effective shield
      against scatter. Factors increasing the minimum height of effective shielding
      included shorter operator, opposite oblique projection of image receptor, and
      shield closer to the face (in horizontal direction).

PMID- 21968818
TI  - RSO Interview with Jeff Dovyak by Rene Michel.

PMID- 21968820
TI  - Dose rate distribution from a standard waste drum arrangement.
AB  - The evaluation of the dose rate distributions from radioactive sources, together
      with the specific detector locations with respect to those sources, in many cases
      presents a significant analytical challenge. With the exception of a few, simple
      source-detector geometries, it is not possible to find an analytical expression
      for these dose rate distributions as functions of detector location. In this
      paper, the dose rate distributions due to the arrangement of radiological waste
      drums on a standard wooden transport and storage pallet are investigated. The
      dose rates at various distances, ranging from 5 cm to 20 m, from the waste drum
      assembly have been evaluated by Monte Carlo calculations. The simulation data are
      fitted by smooth analytical functions in two independent regions, the waste drum
      near zone, where a logarithmic function best described the data, and the far
      zone, where the functional dependence closely approximates the 1/r2-law for point
      sources.

PMID- 21968821
TI  - Radon measurement quality, how accurate is reasonable?
AB  - Until 2006, continuous radon monitoring devices, CR, could either be calibrated
      by reference to known quantities or by internal adjustments and or alignments. In
      2007, a policy was advanced by the National Radon Safety Board and the National
      Environmental Health Association mandating internal adjustment and or alignment.
      Further, calibrations could only be performed by radon chamber persons authorized
      by the specific device manufacturer, which was a process that was impossible for
      many chamber operators to achieve. The paper serves to examine the technical
      validity for routine internal adjustments to Honeywell and Sun Nuclear (Sun
      Nuclear Corporation, 425A Pineda Court, Melbourne, FL 32940-7508) devices in
      contrast to the clear market controlling advantages of the policy. The purpose
      for making radon measurements is to assess risk. Comparing the uncertainties
      associated with risk to counting uncertainties of Honeywell and Sun Nuclear CR
      devices, less than 1% of model 1027 devices would have a calibration error
      exceeding 25%, and those devices, at this Radon Measurement Proficiency limit,
      would produce results that were more precise and accurate than the radon risk
      uncertainty. This was true for CR devices that have not been internally adjusted
      nor corrected in any way. It was concluded that internal adjustment or alignment
      better supported business principles than science.

PMID- 21968822
TI  - Radioactive material shipping for academic and medical facilities.
AB  - This paper is intended as an aid for preparing radioactive material shipments in
      academic and medical facilities. These facilities may only ship radioactive
      materials infrequently. As such, ensuring compliance with applicable regulations
      can be very time consuming. Excepted package shipments (including empty packages)
      and shipments using Type A packages for a select list of isotopes commonly used
      by academic and medical facilities are covered. Tables and flowcharts are used to
      direct one through the process of determining if the material to be shipped meets
      the definition of radioactive material for transportation purposes and if it
      qualifies for excepted package or Type A package shipment. The reader is then
      directed to procedures to properly prepare, document, and ship the radioactive
      material package.

PMID- 21968823
TI  - The U.S. NRC and the ADR process learning experiences.
AB  - This article discusses the regulations and requirements of the U.S. Nuclear
      Regulatory Commission pertaining to the practice of nuclear medicine. Among the
      regulations and requirements to be discussed include the record keeping
      requirements and the information to be made available to the U.S. NRC regularly
      and during inspections. Also examined are the tools and methods that the U.S. NRC
      has made available to resolve any discrepancies with licensees. Lastly reviewed
      are the Alternate Dispute Resolution (ADR) process and the methods that the U.S.
      NRC provides to solve any disputes between it and licensees.

PMID- 21968824
TI  - A plan for the handling of externally contaminated livestock.
AB  - Nuclear accidents and access to radiological weapons for terrorist organizations
      and countries with hostile intentions towards the United States are realistic
      scenarios in the current global landscape. A dispersion of radionuclides can
      result from a nuclear weapon detonation or from a nuclear accident occurring in
      facilities handling or using radioactive material, such as nuclear power
      reactors. Any target of a radiological dispersal device (RDD) or an attack with a
      nuclear weapon and the surrounding area of a reactor accident could be subject to
      a significant amount of fallout and radioactive contamination. Therefore, a
      nuclear event in close proximity to agricultural areas will cause significant
      concern regarding the contamination of food products. In order to respond quickly
      and effectively to a large amount of contaminated agricultural products, such as
      livestock, a prepared and effective plan for handling and processing of these
      products is necessary. A protocol outlining the evaluation of and procedures for
      handling and processing radioactively contaminated livestock is proposed, to
      ensure safe animal food production and economic stability in the livestock
      industry in the wake of such a nuclear or radiological event. An evaluation of
      the salvageability of the contaminated livestock is performed based on the degree
      of exposure, the cost of decontamination, expected demand for food products, and
      economic impact to the owner/producer. Important factors that impact the
      salvageability of affected livestock are listed and analyzed to support the
      decision process for handling contaminated animals.

PMID- 21968825
TI  - First-principle investigation of magnetic coupling mechanism in hypothesized a
      site-ordered perovskite YMn3Sc4O12.
AB  - We have systematically investigated the electronic and magnetic properties of
      hypothesized A-site-ordered perovskite YMn3Sc4O12 using first-principle
      calculation based on the density functional theory. Our calculated results
      predict that YMn3Sc4O12 is both thermodynamically and mechanically stable and its
      ground state is antiferromagnetic insulator. The Mn(3+) is in the high-spin
      state. More importantly, by comparison to YMn3Sc4O12, we point out that the empty
      Sc 3d orbital provides the Mn--O--Sc--O--Mn superexchange interaction, which is
      similar to its isostructural perovskite CaCu3Ti4O12, and enhances the
      antiferromagnetic interaction between Mn ions. From these calculations, we can
      clearly see that the empty 3d orbital plays an important role to realize
      superexchange interaction.

PMID- 21968826
TI  - A microsatellite linkage map of striped bass (Morone saxatilis) reveals conserved
      synteny with the three-spined stickleback (Gasterosteus aculeatus).
AB  - The striped bass (Morone saxatilis) and its relatives (genus Morone) are of great
      importance to fisheries and aquaculture in North America. As part of a
      collaborative effort to employ molecular genetics technologies in striped bass
      breeding programs, we previously developed nearly 500 microsatellite markers. The
      objectives of this study were to construct a microsatellite linkage map of
      striped bass and to examine conserved synteny between striped bass and three
      spined stickleback (Gasterosteus aculeatus). Of 480 microsatellite markers
      screened for polymorphism, 289 informative markers were identified and used to
      genotype two half-sib mapping families. Twenty-six linkage groups were assembled,
      and only two markers remain unlinked. The sex-averaged map spans 1,623.8 cM with
      an average marker density of 5.78 cM per marker. Among 287 striped bass
      microsatellite markers assigned to linkage groups, 169 (58.9%) showed homology to
      sequences on stickleback chromosomes or scaffolds. Comparison between the
      stickleback genome and the striped bass linkage map revealed conserved synteny
      between these two species. This is the first linkage map for any of the Morone
      species. This map will be useful for molecular mapping and marker-assisted
      selection of genes of interest in striped bass breeding programs. The conserved
      synteny between striped bass and stickleback will facilitate fine mapping of
      genome regions of interest and will serve as a new resource for comparative
      mapping with other Perciform fishes such as European sea bass (Dicentrarchus
      labrax), gilthead sea bream (Sparus aurata), and tilapia (Oreochromis ssp.).

PMID- 21968827
TI  - Osteoarthritic change is delayed in a Ctsk-knockout mouse model of
      osteoarthritis.
AB  - OBJECTIVE: Several studies have shown that cathepsin K (CTK) is overexpressed in
      osteoarthritic (OA) cartilage and subchondral bone. However, it has not been well
      established whether CTK expression is harmful or beneficial. We undertook this
      study to investigate the direct involvement of CTK in OA development using Ctsk
      knockout (Ctsk(-/-)) mice in a joint instability-induced model of OA. METHODS: We
      analyzed the natural course of the phenotype of 25-week-old Ctsk(-/-) mice. OA
      development was evaluated with a modified Mankin histologic score up to 8 weeks
      after surgery was performed to destabilize the knee in Ctsk(-/-) and Ctsk(+/+)
      mice. Histologic analysis was used to evaluate expression of CTK, matrix
      metalloproteinase 13 (MMP-13), ADAMTS-5, and tartrate-resistant acid phosphatase
      (TRAP) proteins in chondrocytes, synovial cells, and osteoclasts. Bone
      architecture was analyzed by histomorphometry. RESULTS: Bone mineral content and
      bone volume were higher in Ctsk(-/-) mice at 25 weeks, whereas OA did not develop
      spontaneously in either Ctsk(-/-) or Ctsk(+/+) mice. In a model of
      destabilization-induced OA, OA progression was significantly delayed in Ctsk(-/-)
      mice. CTK was overexpressed in chondrocytes and synovial cells of knee joints
      developing OA in Ctsk(+/+) mice. MMP-13 and ADAMTS-5 were less strongly expressed
      in chondrocytes of Ctsk(-/-) mice, and MMP-13 was less strongly expressed in
      synovial cells. TRAP-positive osteoclasts were overexpressed in Ctsk(-/-) mice.
      CONCLUSION: These results indicate that CTK plays crucial direct roles in the
      early to intermediate stage of OA development. CTK-positive chondrocytes and
      synovial cells may be a possible target to prevent disease progression in OA.

PMID- 21968828
TI  - Multivisceral and standard resections in colorectal cancer.
AB  - PURPOSE: The current study was designed to identify prognostic factors for long
      term survival in patients with advanced colorectal cancer in a consecutive
      cohort. METHODS: A total of 123 patients were operated because of T4 colorectal
      cancer between 1 January 2002 and 31 December 2008 in the Clinic of Surgery, UK
      SH Campus Luebeck. RESULTS: A total of 78 patients underwent a multivisceral
      resection. The postoperative morbidity was elevated in the patient group with
      multivisceral resections (34.6% vs. 26.7%). Nevertheless, we detected no
      significant differences concerning 30 days mortality (7.7% vs. 8.9%; p = 0.815).
      The main prognostic factor that reached significance in the multivariate analysis
      was the possibility to obtain a R0 resection (p < 0.0001) resulting in a 5-year
      survival rate of 55% for patients with curative resection. There were no
      statistically significant differences in 5-year survival between multivisceral
      and non-multivisceral resections (p = 0.608). Also we were not able to detect any
      significant differences for cancer of colonic or rectal origin (p = 0.839), for
      laparoscopic vs. open procedures (p = 0.610), and for emergency vs. planned
      operations (p = 0.674). Moreover, the existence of lymph node metastases was not
      a predictive factor concerning survival as there was no difference between
      patients with and without lymph node metastases (p = 0.658). CONCLUSIONS:
      Multivisceral resections are associated with the same 5-year survival as standard
      resections. Therefore, the aim to perform a R0 resection should always be the
      main goal in surgery for colorectal cancer. In planned operations, a laparoscopic
      approach is justified in selected patients.

PMID- 21968829
TI  - The naturalist and the nuances: Sentimentalism, moral values, and emotional
      expression in Darwin and the anatomists.
AB  - Comparing Charles Darwin's account of emotional expression to previous nineteenth
      century scientific studies on the same subject, this article intends to locate
      the exact nature of Darwin's break in his 1872 book (as well as in his earlier
      notebooks). In contrast to a standard view that approaches this question in the
      framework of the creationism/evolutionism dichotomy, I argue that Darwin's
      account distinguishes itself primarily by its distance toward the sentimentalist
      values and moral hierarchies that were traditionally linked with the study of
      expression--an attitude that is not an inevitable ingredient of the theory of
      evolution. However, Darwin's approach also reintroduces another kind of hierarchy
      in human expression, but one based on attenuation and self-restraint in the
      exhibition of expressive signs.

PMID- 21968830
TI  - Trust in independence: The identities of economists in business magazines, 1945
      1970.

PMID- 21968831
TI  - "Psychoanalysis is good, synthesis is better": the German reception of Freud,
      1930 and 1956.
AB  - Frankfurt's decision to award Freud the Goethe Prize in 1930 as well as the same
      city's decision to celebrate Freud's 100th birthday in 1956 will allow us to
      trace specific traditions in the German encounter with psychoanalysis. The
      diachronic approach will show that certain traditions survived well into the late
      1950s, at a time when West Germany's intellectual landscape was otherwise
      changing on several fronts. Psychoanalysis remained anathema because it did not
      conform with the idealism and holism prevalent in the academic community.

PMID- 21968832
TI  - The attack of psychiatric legitimacy in the 1960s: rhetoric and reality.
AB  - During the 1960s there was a sustained attack on psychiatric legitimacy. Thomas
      S. Szasz was the most vituperative and best-known critic, but he was by no means
      alone. Individuals and groups from both extremes of the political spectrum were
      united in their belief that psychiatry was not a legitimate medical specialty,
      but one that was devoted to protecting its authority as well as enforcing
      societal norms associated with an unjust society. The attack on psychiatry, of
      course, did not occur in a vacuum; numerous social and intellectual currents
      played major roles. To comprehend such attacks and their consequences requires an
      understanding of the larger societal context as well as the changes that
      transformed psychiatry in the post-World War II years.

PMID- 21968838
TI  - On decoding and rewriting genomes: a psychoanalytical reading of a scientific
      revolution.
AB  - In various documents the view emerges that contemporary biotechnosciences are
      currently experiencing a scientific revolution: a massive increase of pace, scale
      and scope. A significant part of the research endeavours involved in this
      scientific upheaval is devoted to understanding and, if possible, ameliorating
      humankind: from our genomes up to our bodies and brains. New developments in
      contemporary technosciences, such as synthetic biology and other genomics and
      "post-genomics" fields, tend to blur the distinctions between prevention, therapy
      and enhancement. An important dimension of this development is "biomimesis": i.e.
      the tendency of novel technologies and materials to mimic or plagiarize nature on
      a molecular and microscopic level in order to optimise prospects for the
      embedding of technological artefacts in natural systems such as human bodies and
      brains. In this paper, these developments are read and assessed from a
      psychoanalytical perspective. Three key concepts from psychoanalysis are used to
      come to terms with what is happening in research laboratories today. After
      assessing the general profile of the current revolution in this manner, I will
      focus on a particular case study, a line of research that may serve as
      exemplification of the vicissitudes of contemporary technosciences, namely viral
      biomaterials. Viral life forms can be genetically modified (their genomes can be
      rewritten) in such a manner that they may be inserted in human bodies in order to
      produce substances at specific sites such as hormones (testosterone),
      neurotransmitters (dopamine), enzymes (insulin) or bone and muscle tissue.
      Notably, certain target groups such as top athletes, soldiers or patients
      suffering from degenerative diseases may become the pioneers serving as research
      subjects for novel applications. The same technologies can be used for various
      purposes ranging from therapy up to prevention and enhancement.

PMID- 21968837
TI  - Regulation of cellular function by connexin hemichannels.
AB  - Gap junctions and hemichannels are formed by a family of proteins called
      connexins. Till date up to twenty one different connexins have been characterized
      and their expression was observed to be spatio-temporally regulated. Gap
      junctions and hemichannels are involved in transfer of a variety of less than 1
      kDa small molecules such as, ions, small metabolites, cAMP, ATP, IP3,
      prostaglandins, etc. Post-translational modifications of connexins and their
      interaction with other proteins are reported to be the key regulators of channel
      functions. Studies during the past decade or so, suggest the physiological
      important of connexin hemichannels mediating the communication between the cell
      and its environment. Molecules conveyed through the hemichannels elicit a variety
      of signaling pathways and influence cellular functions such as, cell cycle,
      tissue homeostasis, migration, mechanotransduction, oxidative stress. The purpose
      of the current review is to compile the reported studies so far and provide a
      general overview in our understanding how the molecular transfer through
      hemichannels regulates cellular signaling and functions.

PMID- 21968839
TI  - Tuberculous cervicitis: A case report.

PMID- 21968840
TI  - A high-throughput automated platform for the development of manufacturing cell
      lines for protein therapeutics.
AB  - The fast-growing biopharmaceutical industry demands speedy development of highly
      efficient and reliable production systems to meet the increasing requirement for
      drug supplies. The generation of production cell lines has traditionally involved
      manual operations that are labor-intensive, low-throughput and vulnerable to
      human errors. We report here an integrated high-throughput and automated platform
      for development of manufacturing cell lines for the production of protein
      therapeutics. The combination of BD FACS Aria Cell Sorter, CloneSelect Imager and
      TECAN Freedom EVO liquid handling system has enabled a high-throughput and more
      efficient cell line development process. In this operation, production host cells
      are first transfected with an expression vector carrying the gene of interest
      (1), followed by the treatment with a selection agent. The stably-transfected
      cells are then stained with fluorescence-labeled anti-human IgG antibody, and are
      subsequently subject to flow cytometry analysis (2-4). Highly productive cells
      are selected based on fluorescence intensity and are isolated by single-cell
      sorting on a BD FACSAria. Colony formation from single-cell stage was detected
      microscopically and a series of time-laps digital images are taken by CloneSelect
      Imager for the documentation of cell line history. After single clones have
      formed, these clones were screened for productivity by ELISA performed on a TECAN
      Freedom EVO liquid handling system. Approximately 2,000 - 10,000 clones can be
      screened per operation cycle with the current system setup. This integrated
      approach has been used to generate high producing Chinese hamster ovary (CHO)
      cell lines for the production of therapeutic monoclonal antibody (mAb) as well as
      their fusion proteins. With the aid of different types of detecting probes, the
      method can be used for developing other protein therapeutics or be applied to
      other production host systems. Comparing to the traditional manual procedure,
      this automated platform demonstrated advantages of significantly increased
      capacity, ensured clonality, traceability in cell line history with electronic
      documentation and much reduced opportunity in operator error.

PMID- 21968845
TI  - Sigmund Freud's evolution from neurology to psychiatry: evidence from his La
      Salpetriere library.
AB  - OBJECTIVE: To analyze the parallel between the scientific evolution of Sigmund
      Freud and his French library during and after his stay with Jean-Martin Charcot
      at La Salpetriere in 1885-1886. METHODS: Systematic review of all identified
      volumes of Freud's personal library, and comparison with his life data and
      publications. RESULTS: The largest part of Freud's 125 French medical books up to
      1900 (of 3,725 books overall) are devoted to hysteria and hypnotism, published
      mainly between 1885 and 1895. Over one-third (50) of the neurology (94) and
      alienism (22) books have Charcot or one of his direct pupils (Janet, Fere,
      Babinski, Gilles de la Tourette, Richer, Pitres, Sollier, Raymond, Marie, Binet,
      Ball, Bourneville, Blocq, Berbez, Guinon, and Souques) as author. During that
      period, Freud evolved from the clinical-anatomic method (after mainly
      experimental histologic studies) to theoretical neurology (using hysteria and
      aphasia models) and psychology, a process which subsequently led to the birth of
      psychoanalysis. CONCLUSION: The library of Freud gives an interesting account on
      his own evolving thinking, which led him to leave neurology for psychology and
      psychoanalysis.

PMID- 21968843
TI  - Preterm birth and risk of epilepsy in Swedish adults.
AB  - OBJECTIVE: To determine whether preterm birth is associated with epilepsy in a
      national cohort of adults aged 25-37 years. METHODS: We conducted a national
      cohort study of 630,090 infants born in Sweden from 1973 through 1979, including
      27,953 born preterm (<37 weeks), followed from 2005 to 2009 for 1)
      hospitalization for epilepsy and 2) outpatient and inpatient prescription of
      antiepileptic drugs. Epilepsy diagnoses and medication data were obtained from
      all hospitals and pharmacies throughout Sweden. RESULTS: We found a strong
      association between preterm birth and epilepsy that increased by earlier
      gestational age. After adjusting for fetal growth and potential confounders, odds
      ratios for hospitalization for epilepsy were 4.98 (95%confidence interval [CI]
      2.87-8.62) for those born at 23-31 weeks, 1.98 (95% CI 1.26-3.13) for those born
      at 32-34 weeks, and 1.76 (95% CI 1.30-2.38) for those born at 35-36 weeks,
      relative to those born full-term (37-42 weeks). A similar but slightly weaker
      trend was observed for the association between preterm birth and antiepileptic
      drug prescription. These associations persisted after excluding individuals with
      cerebral palsy, inflammatory diseases of the CNS, cerebrovascular disease, and
      brain tumors. CONCLUSIONS: These findings suggest that preterm birth, including
      late preterm birth, is strongly associated with epilepsy in Swedish adults aged
      25-37 years. This association was independent of fetal growth and was not
      mediated by cerebral palsy or other comorbidities.

PMID- 21968846
TI  - An embolic bow hunter's stroke associated with anomaly of cervical spine.

PMID- 21968847
TI  - Sun exposure and vitamin D are independent risk factors for CNS demyelination.

PMID- 21968849
TI  - Teaching neuroimages: remote cerebellar hemorrhage following resection of a
      supratentorial tumor.

PMID- 21968850
TI  - Teaching neuroimages: glossopharyngeal neuralgia with syncope: heart rate and
      blood pressure change.

PMID- 21968851
TI  - Dinuclear and 1D iron(III) Schiff base complexes bridged by 4-salicylideneamino
      1,2,4-triazolate: X-ray structures and magnetic properties.
AB  - Four new iron(III) complexes were obtained by the reaction of 4-salicylideneamino
      1,2,4-triazole (Hsaltrz) and selected dinuclear MU-oxo-bridged iron(III) Schiff
      base complexes [{FeL(4)}(2)(MU-O)], where L(4) represents a terminal tetradentate
      dianionic Schiff-base ligand. X-ray structural analysis revealed a novel bridging
      mode of kappaN,kappaO of the saltrz ligand to form dinuclear complexes
      [{Fe(salen)(MU-saltrz)}(2)].CH(3)OH (1) (H(2)salen = N,N'
      ethylenebis(salicylimine)) and [{Fe(salpn)(MU-saltrz)}(2)] (2) (H(2)salpn = N,N'
      1,2-propylenbis(salicylimine)), whereas one-dimensional (1D) zig-zag chains were
      formed in the case of [{Fe(salch)(MU-saltrz)}.0.5CH(3)OH](n) (3) (H(2)salch =
      N,N'-cyclohexanebis(salicylimine)) and [Fe(salophen)(MU-saltrz)](n) (4)
      (H(2)salophen = N,N'-o-phenylenebis(salicylimine)). It was also shown that the
      rigidity of the terminal ligand L(4) can be considered as the key factor for the
      molecular dimensionality of the products. The thorough magnetic analysis based on
      SQUID experiments, including the isotropic exchange and the zero-field splitting
      of both temperature and field dependent data, was performed for dimeric (1 and 2)
      and also for polymeric compounds (3 and 4) and revealed weak antiferromagnetic
      exchange mediated by the saltrz anions with much larger D-parameter (|D|?|J|).

PMID- 21968853
TI  - Vitamin D supplementation versus combined calcium and vitamin D in older female
      patients - an observational study.
AB  - BACKGROUND: In most developed countries overt vitamin D deficiency, characterized
      by rickets or osteomalacia, is now uncommon. However, subclinical vitamin D
      insufficiency is extremely common and may contribute to the development of
      skeletal and non-skeletal problems. Standard practice involves supplementation
      with a combination of vitamin D and calcium although the benefit of adding
      calcium to vitamin D supplements has not been fully established and may reduce
      adherence due to its bulky and chalky consistency. PURPOSE OF STUDY: To compare
      the effects of vitamin D alone versus vitamin D/calcium supplements on vitamin D
      levels, bone profile and parathyroid hormone level. POPULATION: Older (> 65
      years) female patients living in the community and long term care institutions.
      INTERVENTIONS: Either 800 iu of vitamin D3 or a composite supplement of 800 iu
      vitamin D3 and 1000 mg calcium were given to patients in an open-labelled
      observational study. Serum 25-hydroxy-vitamin D, parathyroid hormone, calcium,
      phosphate and alkaline phosphatase levels were assessed at baseline and after 3
      months of treatment. RESULTS: Serum 25-hydroxy-vitamin D levels rose from
      baseline levels of 25 +/- 16 to 79 +/- 16 in those treated with vitamin D alone
      and from 35 +/- 24 nmol/L to 70 +/- 24 nmol/L in those treated with vitamin D and
      calcium. Serum PTH levels fell by similar amounts in both groups. In both
      community dwellers and institutionalised patients, those treated with vitamin D
      alone were at least as likely to achieve normalisation of serum vitamin D levels
      as those on combined calcium/vitamin D treatment. CONCLUSION: Vitamin D alone
      appears as effective as combined calcium/vitamin D treatment in restoring serum
      vitamin D levels in older community dwelling and institutionalised patients. A
      prospective randomised trial would help confirm these findings.

PMID- 21968852
TI  - Nutrition in the age-related disablement process.
AB  - The transition from independence to disability in older adults is characterized
      by detectable changes in body composition and physical function. Epidemiologic
      studies have shown that weight loss, reduced caloric intake and the reduced
      intake of specific nutrients are associated with such changes. The mechanisms
      underlying these associations remain unclear, and different hypotheses have been
      suggested, including the reduction of the antioxidant effects of some nutrients.
      Changes in muscle mass and quality might play a central role in the pathway
      linking malnutrition, its biological and molecular consequences, and function. A
      different approach aims at assessing diets by dietary patterns, which capture
      intercorrelations of nutrients within a diet, rather than by selective foods or
      nutrients: epidemiologic evidence suggests that some types of diet, such as the
      Mediterranean diet, might prevent negative functional outcomes in older adults.
      However, despite a theoretical and empirical basis, intervention studies using
      nutritional supplementation have shown inconclusive results in preventing
      functional impairment and disability. The present work is the result of a review
      and consensus effort of a European task force on nutrition in the elderly,
      promoted by the International Association of Gerontology and Geriatrics (IAGG)
      European Region. After the critical review of different aspects related to the
      role of nutrition in the transition from independence to disability, we propose
      future lines for research, including the determination of levels of inadequacy
      and target doses of supplements, the study of interactions (between nutrients
      within a diet and with other lifestyle aspects), and the association with
      functional outcomes.

PMID- 21968854
TI  - Incidence and predictive factors of depressive symptoms in Alzheimer's disease:
      the REAL.FR study.
AB  - BACKGROUND: Many patients develop psychiatric and behavioral disturbances in the
      course of Alzheimer's disease (AD). Among these disturbances, depressive symptoms
      are frequent and affect nearly 40% of patients. The natural history and course of
      such symptoms in AD, and in particular the predictive factors, are little known.
      We studied the incidence and risk factors for the development of the first
      depressive symptoms in AD. DESIGN: Multicenter prospective study. PARTICIPANTS:
      Three hundred twelve AD patients from the French Network on AD (REAL.FR) without
      depression and without antidepressant treatment at baseline were followed up and
      assessed every 6 months for 4 years. During follow-up, all events occurring
      between two visits were carefully recorded. MEASUREMENTS: We used the
      Neuropsychiatric Inventory (NPI) for comprehensive evaluation of behavioral and
      psychological symptoms and depressive symptoms in particular. A multivariate
      analysis was performed using a backward stepwise Cox proportional hazards model.
      RESULTS: The incidence of depressive symptoms was 17.45% person/years, 95%CI
      (13.88-21.02). Among non-time dependent variables, duration of disease (RR=0.51;
      95%CI: 0.30-0.85, p=0.0102) and the number of comorbid conditions (RR=0.45;
      95%CI: 0.24-0.83, p=0.0115) were protective factors against the development of
      depressive symptoms. Agitation/aggression (RR=1.96; 95%CI: 1.19-3.23, p=0.0078)
      and sleep disturbances (RR=2.65; 95%CI: 1.40-5.00, p=0.0026) were time-dependent
      variables predictive of depressive symptoms. CONCLUSION: Better knowledge of
      predictive factors of mood disturbances in AD will enable clinicians to set up
      appropriate management of their patients. As published longitudinal studies are
      few, further works should be carried out to improve knowledge of the pattern and
      course of depression and depressive symptoms in AD.

PMID- 21968855
TI  - Better cognitive and physical performance is associated with higher blood
      pressure in centenarians.
AB  - OBJECTIVES: Knowledge of rational, evidence based health care in the hundred-year
      old is still poor. The aim of the study was to evaluate health and functional
      state in hundred-year-old inhabitants of Upper Silesia, Poland, with a focus on
      the heart and vascular function. PARTICIPANTS: Medical and nursing assessment at
      places of residence was performed in thirty five 100.7+/-1.4 (mean+/-SD) year-old
      subjects, 28 women, and 7 men. MEASUREMENTS: The protocol included Mini-Mental
      State Examination (MMSE), Barthel Index (BI) and laboratory tests. A telephone
      follow-up was performed 180 days after the initial examination. RESULTS: Most
      subjects had increased systolic blood pressure (BP), diminished albumin and
      folate serum levels as well as decreased Glomerular Filtration Rate. According to
      the quadratic polynomial regression model MMSE and BI were dependent on BP.
      Higher BP was associated with better performance and survival. Those who survived
      more than 180 days had lower levels of CRP and VCAM-1 and higher level of sCD40L.
      CONCLUSION: The relationships between functional scales, survival and blood
      pressure suggest a beneficial effect of elevated BP on both mental and physical
      performance in centenarians. Further studies should determine an optimal balance
      between risk and benefits of elevated blood pressure in the oldest old people.

PMID- 21968856
TI  - Intensive dietary intervention by a dietitian as a case manager among community
      dwelling older adults: the EDIT study.
AB  - BACKGROUND: Clinical trials that have assessed the best approach for treating
      under-nutrition in old age are scarce. OBJECTIVE: To determine the impact of an
      intensive nutritional intervention program led by a dietitian on the health and
      nutritional status of malnourished community dwelling older adults. METHODS:
      Sixty-eight eligible participants (age<75) were randomly assigned to a Dietetic
      Intervention Treatment (DIT), an intensive nutritional intervention led by a
      dietitian, or a Medical Treatment (MT), a physician-led standard care group, with
      an educational booklet regarding dietary requirements and recommendations for
      older adults. An additional 59 eligible participants who were unable to
      participate in the randomization were included as a non-randomized "untreated
      nutrition" group (UNG). RESULTS: Over the 6-month follow-up, the DIT group showed
      significant improvement in cognitive function (from 25.8+/-4.5 to 26.8+/-4,
      p=0.04), and depression score (from 7.3+/-3.9 to 5.4+/-3.9, p=0.04) compared with
      the change in the other 2 groups. The DIT group showed a significant improvement
      in intake of carbohydrates (+15% vs. +1% in the MT and +3% in the UNG), protein
      (+8% vs. +2% in the MT and -3% in the UNG), vitamin B6 (+20% vs. +7% in the MT
      and +8% in the UNG), and vitamin B1 (+22% vs. +11% in the MT and 0% in the UNG).
      The DIT group had a significantly lower cost of physician visits than the other 2
      groups ($172.1+/-232.0 vs. $417.2+/-368.0 in the MT and $428.1+/-382.3 in the
      UNG, p=0.005). CONCLUSION: Intensive dietary intervention was moderately
      effective in lowering cost of services used and improving medical and nutritional
      status among community dwelling older adults.

PMID- 21968857
TI  - Study on factors affecting the occurrence of upper gastrointestinal bleeding in
      elderly acute stroke patients undergoing rehabilitation.
AB  - OBJECTIVE: To investigate factors affecting upper gastrointestinal bleeding
      (UGIB) in elderly first-time acute stroke patients undergoing rehabilitation.
      PARTICIPANTS AND SETTING: Three hundred and thirty-one elderly first-time acute
      stroke patients (age >=65 years) transferred to our rehabilitative ward from July
      2002 to June 2009 were included in the study. DESIGN: We divided patients into
      UGIB and non-UGIB groups. Demographic data and possible precipitating factors
      were analyzed. RESULTS: Sixty-eight (20.5%) patients experienced UGIB. The
      patients with UGIB were of older age (75.4 vs. 72.92 years, P = 0.003), had a
      longer rehabilitative ward stay (26.32 vs. 21 days, P = 0.002), more frequently
      had stroke-induced consciousness impairment (60.3 vs. 38%, P = 0.001), had a
      higher incidence of bilateral brain lesion (7.4 vs. 1.9%, P = 0.034), and more
      frequently used anticoagulants (17.6 vs. 9.1%, P = 0.044) than patients in the
      non-UGIB group. In multivariate logistic regression analysis, stroke-induced
      impaired consciousness (odds ratio: 2.806, 95% CI = 1.588-4.957, P = 0.000) was
      the most important risk factor for UGIB. CONCLUSIONS: UGIB may prolong a
      patient's length of stay in a rehabilitative ward. These identified factors may
      help clinicians identify risks of UGIB before it develops.

PMID- 21968858
TI  - First-generation versus third-generation comprehensive geriatric assessment
      instruments in the acute hospital setting: a comparison of the Minimum Geriatric
      Screening Tools (MGST) and the interRAI Acute Care (interRAI AC).
AB  - OBJECTIVE: Comparison of the first-generation Minimum Geriatric Screening Tools
      (MGST) and the third-generation interRAI Acute Care (interRAI AC). DESIGN: Based
      on a qualitative multiphase exchange of expert opinion, published evidence was
      critically analyzed and translated into a consensus. RESULTS: Both methods are
      intended for a multi-domain geriatric assessment in acute hospital settings, but
      each with a different scope and goal. MGST contains a collection of single
      domain, internationally validated instruments. Assessment is usually triggered by
      care givers' clinical impression based on geriatric expertise. A limited
      selection of domains is usually assessed only once, by disciplines with domain
      specific expertise. Clinical use results in improvement to screen geriatric
      problems. InterRAI AC, tailored for acute settings, intends to screen a large
      number of geriatric domains. Based on systematic observational data, risk domains
      are triggered and clinical guidelines are suggested. Multiple observation periods
      outline the evolution of patients' functioning over stay in comparison to the
      premorbid situation. The method is appropriate for application on geriatric and
      non-geriatric wards, filling geriatric knowledge gaps. The interRAI Suite
      contains a common set of standardized items across settings, facilitating data
      transfer in transitional care. CONCLUSION: The third-generation interRAI AC has
      advantages compared to the first-generation MGST. A cascade system is proposed to
      integrate both, complementary methods in practice. The systematic interRAI AC
      assessment detects risk domains. Subsequently, clinical protocols suggest
      components of the MGST as additional assessment. This cascade approach unites the
      strength of exhaustive assessment of the interRAI AC with domain-specific tools
      of the MGST.

PMID- 21968860
TI  - The multidimentionality of frailty: many faces of one single dice.

PMID- 21968861
TI  - Frailty and cognitive decline: links, mechanisms and future directions.

PMID- 21968859
TI  - Reducing "iatrogenic disability" in the hospitalized frail elderly.
AB  - BACKGROUND: Hospitalization is the first cause of functional decline in the
      elderly: 30 to 60% of elderly patients lose some independence in basic activities
      of daily living (ADL) during a stay in hospital. This loss of independence
      results from the acute condition that led to admission, but is also related to
      the mode of management. OBJECTIVE: This paper is a review of the literature on
      functional decline in elderly hospitalized patients. It is the first stage in a
      project aiming to prevent dependence that is induced during the course of care.
      METHODS: During a 2-day workshop in Monaco, a task force of 20 international
      experts discussed and defined the concept of "iatrogenic disability". RESULTS: 1-
      "Iatrogenic disability" was defined by the task force as the avoidable dependence
      which often occurs during the course of care. It involves three components that
      interact and have a cumulative effect: a) the patient's pre-existing frailty, b)
      the severity of the disorder that led to the patient's admission, and lastly c)
      the hospital structure and the process of care. 2- The prevention of "iatrogenic
      disability" involves successive stages. - becoming aware that hospitalization may
      induce dependence. Epidemiological studies have identified at-risk populations by
      the use of composite scores (HARP, ISAR, SHERPA, COMPRI, etc). - considering that
      functional decline is not a fatality. Quality references have already been
      defined. Interventions to prevent dependence in targeted populations have been
      set up: simple geriatric consultation teams, single-factor interventions (aimed
      for example at mobility, delirium, iatrogenic disorders) or multidomain
      interventions (such as GEM and ACE units, HELP, Fast Track, NICHE). These
      interventions are essentially centered on the patient's frailty and have limited
      results, as they take little account of the way the institution functions, which
      is not aimed at prevention of functional decline. The process of care reveals
      shortcomings: lack of geriatric knowledge, inadequate evaluation and management
      of functional status. The group suggests that interventions must not only
      identify at-risk patients so that they may benefit from specialized management,
      but they must also target the hospital structure and the process of care. This
      requires a graded "quality approach" and rethinking of the organization of the
      hospital around the elderly person.

PMID- 21968862
TI  - Frailty: diagnosis and management.

PMID- 21968863
TI  - Effect of a medical food on body mass index and activities of daily living in
      patients with Alzheimer's disease: secondary analyses from a randomized,
      controlled trial.
AB  - OBJECTIVES: To investigate the effect of a medical food (Souvenaid) on body mass
      index (BMI) and functional abilities in patients with mild Alzheimer's disease
      (AD). DESIGN/SETTING/PARTICIPANTS/INTERVENTION /MEASUREMENTS: These analyses were
      performed on data from a 12-week, double-blind, randomized, controlled,
      multicenter, proof-of-concept study with a similarly designed and exploratory 12
      week extension period. Patients with mild AD (Mini-Mental State Examination score
      of 20-26) were randomized to receive either the active product or an iso-caloric
      control product. While primary outcomes included measures of cognition, the 23
      item Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL)
      scale was included as a secondary outcome. Both ADCS-ADL and BMI were assessed at
      baseline and Weeks 6, 12 and 24. Data were analyzed using a repeated-measures
      mixed model. RESULTS: Overall, data suggested an increased BMI in the active
      versus the control group at Week 24 (ITT: p = 0.07; PP: p = 0.03), but no
      treatment effect on ADCS-ADL was observed. However, baseline BMI was found to be
      a significant treatment effect modifier (ITT: p = 0.04; PP: p = 0.05), and an
      increase in ADCS-ADL was observed at Week 12 in patients with a 'low' baseline
      BMI (ITT: p = 0.02; PP: p = 0.04). CONCLUSIONS: These data indicate that baseline
      BMI significantly impacts the effect of Souvenaid on functional abilities. In
      addition, there was a suggestion that Souvenaid increased BMI.

PMID- 21968864
TI  - Frailty, cognitive impairment and mortality among the oldest old.
AB  - INTRODUCTION: Both frailty and cognitive impairment are increasingly prevalent
      with advancing age. Nonetheless among the oldest old their relationship is poorly
      described. This study examines the association between frailty status and
      cognitive impairment at age 85 and their impact on 5-year mortality. METHODS: A
      representative sample of 840 community dwelling people from the Jerusalem
      Longitudinal Cohort Study was comprehensively assessed at age 85. Frailty was
      defined according to the "phenotype of frailty", as including at least three of
      the following: weight loss, slowness, weakness, exhaustion and low physical
      activity levels. Pre frailty was defined as 1-2/5 criteria. Cognitive impairment
      was assessed according to the Mini Mental State Examination (MMSE). Mortality
      data was collected from age 85-90. RESULTS: A total of 164 (19.5%) were frail,
      470 (56%) were pre frail and 206 (24.5%) were not frail, with prevalence of
      MMSE<=24 being 53.3%, 15%, and 7.4% respectively. A uniform pattern of increased
      adverse health, affective, disease and functional measures were associated with
      frailty status. Frailty status was significantly associated with cognitive
      impairment, with an Odds Ratios of 3.77 (95%CI 1.42-9.99) for MMSE<=24 after
      adjustment for socio demographic, medical mood and functional covariates. Among
      frail, pre frail and non frail subjects, 5-year mortality was 44.5%, 20.4%, 13.6%
      respectively. Mortality among frail subjects with or without cognitive impairment
      was 54.2% vs. 54.9%, p=0.9). Adjusting together for frailty, MMSE, education and
      gender, the Hazards ratio for 5-year mortality for frailty was 3.861 (95%CI 2.4
      6.2), and for MMSE<=24 was 1.25 (95%CI 0.87-1.78). CONCLUSIONS: Among the oldest
      old, frailty status was significantly associated with cognitive impairment; after
      adjustment, frailty alone was predictive of subsequent mortality.

PMID- 21968865
TI  - Cognitive impairment and low physical activity are the components of frailty more
      strongly associated with disability.
AB  - OBJECTIVE: To determine the association of the five frailty criteria from the
      Cardiovascular Health Study, as well as cognitive impairment, with prevalent
      disability for the instrumental (IADL) and basic activities of daily living
      (ADL). DESIGN: Cross-sectional study of 475 community-dwelling subjects aged 70
      and older, participating in the Mexican Study of Nutritional and Psychosocial
      Markers of Frailty. MEASUREMENTS: Six probable frailty criteria were considered:
      weight loss, poor endurance, low physical activity, slowness, weakness, and
      cognitive impairment. The association of each component of frailty for IADL and
      ADL disability as main outcomes was determined constructing multivariate logistic
      regression analyses. Final models were adjusted by socio-demographic factors and
      the presence of the other five frailty components as covariates. RESULTS: Mean
      age of participants was 78.1 (SD=6.2). The unadjusted results showed that each of
      the components of frailty, except weight loss, was associated with both IADL and
      ADL disability. However, after adjustment, only low physical activity [Odds ratio
      (OR) =3.27; 95% CI=1.56 to 6.85] and cognitive impairment (OR=2.06; 95% CI=1.04
      to 4.06) remain independently associated with IADL disability. Regarding ADL
      disability, only a lower physical activity (OR=7.72; 95% CI=1.28 to 46.46) was
      associated with this outcome, whereas cognitive impairment was marginally
      associated but was not statistically significant (OR=5.45; 95% CI=0.91 to 32.57).
      CONCLUSIONS: Cognitive impairment and low physical activity are the main
      contributing factors of frailty phenotype to disability. Better understanding the
      independent contribution of each frailty subdimension to the different adverse
      health outcomes may help to provide a more adequate management of frail elderly.

PMID- 21968866
TI  - Physical frailty predicts future cognitive decline - a four-year prospective
      study in 2737 cognitively normal older adults.
AB  - OBJECTIVE: To examine the association between baseline frailty measurements and
      cognitive function 4 years later. DESIGN: Prospective observational study.
      SETTING: Community. PARTICIPANTS: Two thousand seven hundred and thirty seven
      cognitively normal older adults. MEASUREMENT: The appendicular muscle mass (ASM),
      hand grip strength, timed chair-stand test, walking speed and step length were
      measured at baseline. The Mini-mental state examination (MMSE) was administered
      at baseline and 4 years later. RESULTS: In men, all baseline frailty
      measurements, namely, being underweight, lower ASM, weaker grip strength, slower
      chair-stand test, shorter step length, slower timed walk were significantly
      associated with a lower MMSE score 4 years afterwards. After adjustment for age,
      years of education and baseline MMSE score, ASM and timed walk became
      insignificant. In women, all frailty measurements except underweight and low ASM
      were significantly associated with MMSE score 4 years later. Moreover, only
      weaker grip strength persisted to be significant after adjustment for age, years
      of education and baseline MMSE score. CONCLUSION: Physical frailty, as
      represented by being underweight, weaker grip strength, slower chair-stand test,
      shorter step-length in men and weaker grip strength in women, was associated with
      cognitive decline over a four year period.

PMID- 21968867
TI  - Sex differences in the association between muscle quality, inflammatory markers,
      and cognitive decline.
AB  - OBJECTIVE: Aspects of frailty such as sarcopenia and dementia are associated with
      a proinflammatory state; however, little research has examined the concurrence of
      these pathologies. This study examined sex-specific differences in the
      relationship between low muscle quality and impaired cognitive functioning, while
      considering the role of inflammatory markers. DESIGN: The nationally
      representative sample was drawn from a cross-sectional study. PARTICIPANTS: Four
      hundred forty-five females and four hundred twenty-two males over age 60 from the
      National Health and Nutrition Examination Survey for 2001-2002 were included.
      MEASUREMENTS: Muscle quality was calculated as isokinetic strength per unit
      muscle mass. Skeletal muscle mass of the legs was measured using dual energy x
      ray absorptiometry and isokinetic strength of the knee extensors was estimated
      using a Kin-Com dynamometer. Participants were assessed for cognitive functioning
      using the Wechsler Adult Intelligence Scale, Third Edition (WAIS-III) Digit
      Symbol - Coding module. High sensitivity C-reactive protein (CRP) assays were
      performed on blood samples using a Behring Nephelometer to estimate levels of
      inflammation. Sex stratified ordinary least squares regression models were
      utilized to estimate the relationship between muscle quality and cognitive
      functioning, while examining CRP as a possible mechanism and controlling for
      potential confounds. RESULTS: In the first model a statistically significant
      positive relationship was found between cognitive functioning and muscle quality
      for both sex groups. In the second model, CRP was found to have a statistically
      significant negative association with cognitive functioning for females but not
      males. Furthermore, the inclusion of CRP in the second model significantly
      reduced the predictive power of muscle quality for females, as compared to model
      1. CONCLUSION: Measures of sarcopenia are associated with lower cognitive
      functioning in older adults, and for females, this association may be partly due
      to systemic inflammation. Further research is need to examine the relationship
      between these frailty-related pathologies, which have substantial health and
      economic implications.

PMID- 21968868
TI  - Rapid cognitive decline, one-year institutional admission and one-year mortality:
      analysis of the ability to predict and inter-tool agreement of four validated
      clinical frailty indexes in the SAFEs cohort.
AB  - OBJECTIVES: To evaluate the predictive ability of four clinical frailty indexes
      as regards one-year rapid cognitive decline (RCD - defined as the loss of at
      least 3 points on the MMSE score), and one-year institutional admission (IA) and
      mortality respectively; and to measure their agreement for identifying groups at
      risk of these severe outcomes. DESIGN: One-year follow-up and multicentre study
      of old patients participating in the SAFEs cohort study. SETTING: Nine university
      hospitals in France. PARTICIPANTS: 1,306 patients aged 75 or older (mean age 85+/
      6 years; 65% female) hospitalized in medical divisions through an Emergency
      department. MEASUREMENTS: Four frailty indexes (Winograd; Rockwood; Donini; and
      Schoevaerdts) reflecting the multidimensionality of the frailty concept, using an
      ordinal scoring system able to discriminate different grades of frailty, and
      constructed based on the accumulation of identified deficits after comprehensive
      geriatric assessment conducted during the first week of hospital stay, were used
      to categorize participants into three different grades of frailty: G1 - not
      frail; G2 - moderately frail; and G3 - severely frail. Comparisons between groups
      were performed using Fisher's exact test. Agreement between indexes was evaluated
      using Cohen's Kappa coefficient. RESULTS: All patients were classified as frail
      by at least one of the four indexes. The Winograd and Rockwood indexes mainly
      classified subjects as G2 (85% and 96%), and the Donini and Schoevaerdts indexes
      mainly as G3 (71% and 67%). Among the SAFEs cohort population, 250, 1047 and
      1,306 subjects were eligible for analyses of predictability for RCD, 1-year IA
      and 1-year mortality respectively. At 1 year, 84 subjects (34%) experienced RCD,
      377 (36%) were admitted into an institutional setting, and 445 (34%) had died.
      With the Rockwood index, all subjects who experienced RCD were classified in G2;
      and in G2 and G3 when the Donini and Schoevaerdts indexes were used. No
      significant difference was found between frailty grade and RCD, whereas frailty
      grade was significantly associated with an increased risk of IA and death,
      whatever the frailty index considered. Agreement between the different indexes of
      frailty was poor with Kappa coefficients ranging from -0.02 to 0.15. CONCLUSION:
      These findings confirm the poor clinimetric properties of these current indexes
      to measure frailty, underlining the fact that further work is needed to develop a
      better and more widely-accepted definition of frailty and therefore a better
      understanding of its pathophysiology.

PMID- 21968869
TI  - Cognitive function is associated with body composition and nutritional risk of
      geriatric patients.
AB  - BACKGROUND: Most patients with dementia lose body weight over the course of the
      disease. Yet it is not known whether this weight loss is predominantly in the
      form of fat-free mass (FFM) or fat mass (FM), the latter of which one would
      expect if the weight loss were caused simply by a chronic decrease of energy
      intake. OBJECTIVES: To determine body composition and nutritional risk in
      geriatric patients and their association with cognitive function. DESIGN: A
      retrospective, cross-sectional single-center database analysis. METHODS: We
      analyzed 4,095 consecutive geriatric hospital patients for body composition,
      nutritional risk, need of care and cognitive function using bioelectric impedance
      analysis, NRS 2002, Barthel Index and Mini Mental State Examination. RESULTS:
      Subjects with cognitive dysfunction showed significant lower body weight, body
      mass index (BMI), FM, fat mass index, FFM and fat-free mass index and a higher
      NRS score compared to cognitively intact subjects. Mean body weight decreased
      10.2%, mean FM decreased 21.1%, mean FFM decreased 5.9% and mean NRS 2002 score
      increased from 2.1 to 3.0 points with increasing cognitive deterioration. A
      multivariate analysis revealed that cognitive dysfunction, age and female gender
      were all significant risk factors for a low body mass index and a low fat mass
      index. Age, male gender and need of care, but not cognitive dysfunction, were
      risk factors for a low fat-free mass index. CONCLUSION: Dementia patients seem to
      lose predominantly fat mass with weight loss. Female dementia patients are at a
      higher nutritional risk than male patients, presumably as a result of their
      different social situation in old age. That is why the nutritional state of
      female patients with dementia requires special attention.

PMID- 21968871
TI  - Efficacy of a medical food on cognition in Alzheimer's disease: results from
      secondary analyses of a randomized, controlled trial.
AB  - OBJECTIVE: To investigate the extent that baseline cognitive impairment and
      intake adherence affected the 13-item Alzheimer's Disease Assessment Scale -
      cognitive subscale (ADAS-cog) intervention response of a medical food in
      Alzheimer's Disease (AD) patients. DESIGN/SETTING/PARTICIPANTS
      /INTERVENTION/MEASUREMENTS: This analysis was performed on data from a proof-of
      concept study, consisting of a 12-week, double-blind, randomized, controlled,
      multicenter trial, followed by a similarly designed 12-week extension study.
      Patients with mild AD (Mini-Mental State Examination [MMSE] score of 20-26) were
      randomized to receive active or control product as a 125 ml daily drink. One of
      the co-primary outcome measures was the 13-item ADAS-cog. In this analysis, the
      study population was divided into two subgroups: patients with 'low' baseline
      ADAS-cog scores (<25.0) and patients with 'high' baseline ADAS-cog scores
      (>=25.0). Repeated Measures Models (RMM) were used to determine the relationship
      between ADAS-cog score and intervention. RESULTS: A significant treatment effect
      (F[1,319]=4.0, p=0.046) was shown in patients with 'high' baseline ADAS-cog, but
      not in patients with 'low' baseline ADAS-cog (F[1,250]=1.25, p=0.265). Overall,
      intake adherence was significantly correlated with ADAS-cog improvement in the
      active product group (correlation coefficient=-0.260; p=0.019), but not the
      control group. CONCLUSION: These data indicate that baseline ADAS-cog
      significantly influenced the effect of Souvenaid intervention on ADAS-cog
      outcome. A higher intake of active study product was also associated with greater
      cognitive benefit. These findings highlight the potential benefits of Souvenaid
      in AD patients and warrant confirmation in larger, controlled studies.

PMID- 21968870
TI  - Different models of frailty in predementia and dementia syndromes.
AB  - Dementia is an increasingly common disease in the aging population, and the
      numbers are expected to rise exponentially in coming years. Therefore, there is a
      critical need to potentially individualize new strategies able to prevent and to
      slow down the progression of predementia and dementia syndromes. Despite a
      substantial increase in the epidemiological and clinical evidence on frailty,
      there is no consensus on its definition or on what criteria should be used to
      identify older individuals with frailty. Frailty appears to be a nonspecific
      state of vulnerability, which reflects multisystem physiological change. In fact,
      current thinking is that not only physical but also psychological, cognitive and
      social factors contribute to this multidimensional syndrome and need to be taken
      into account in its definition and treatment. Cognition has already been
      considered as a component of frailty, and it has been demonstrated that it is
      associated with adverse health outcomes. In a recent population-based study,
      physical frail demented patients were at higher risk of all-cause mortality over
      3- and 7-year follow-up periods. Several studies have also reported that physical
      frailty is associated with low cognitive performance, incidence of Alzheimer's
      disease (AD), and mild cognitive impairment, and AD pathology in older persons
      with and without dementia. Most frailty instruments use a dichotomous scoring
      system classifying a person as either frail or not frail, while a continuous or
      an ordinal scoring system on multiple levels would be preferable to be used as an
      outcome measure. Recently, a Multidimensional Prognostic Index (MPI), derived
      from a standardized comprehensive geriatric assessment, was effective in
      predicting short- and long-term mortality risk in hospitalized patients with
      dementia. Overall taken together these findings supported the concept that
      outcome measures linked to multidimensional impairment may be extremely important
      in making clinical decisions, especially for monitoring drug treatment in
      randomized clinical trials also for predementia and dementia syndromes.

PMID- 21968872
TI  - Designing Phase II B trials in sarcopenia: the best target population.
AB  - Despite the existing limitations and controversies regarding the definition of
      sarcopenia and its clinical consequences, the current scientific evidence
      strongly suggests that muscle decline is a primary determinant of the disabling
      process (and likely of other major health-related events). In fact, the muscle
      loss (in terms of mass as well as strength) occurring with aging has been
      growingly associated with mobility impairment and disability in older persons.
      Unfortunately, current evidence is mainly from observational studies. Times are
      mature to begin testing interventions aimed at modifying the sarcopenia process
      through the design and development of specific clinical trials. Considering the
      emergence of many promising interventions towards this age-related condition
      (e.g., physical exercise [in particular, resistance training], testosterone,
      antioxidant supplementations), the need for Phase II trial designs is high. In
      the present report, we discuss which are the major issues related to the design
      of Phase II clinical trials on sarcopenia with particular focus on the
      participant's characteristics to be considered as possible inclusion and
      exclusion criteria.

PMID- 21968873
TI  - Grip work estimation during sustained maximal contraction: validity and
      relationship with dependency and inflammation in elderly persons.
AB  - OBJECTIVES: To validate muscle endurance estimation and to examine relationships
      with dependency and inflammation in elderly persons. DESIGN: Cross sectional
      validation and explorative study. SETTING: Hospitalized geriatric patients and
      community-dwelling controls. PARTICIPANTS: 91 elderly patients (aged 83+/-5
      years), 100 elderly controls (aged 74+/-5 years) and 100 young controls (aged
      23+/-3 years). MEASUREMENTS: Grip strength (GS) was recorded continuously during
      sustained maximal contraction until exhaustion. Fatigue resistance (FR) was
      expressed as the time during which GS drops to 50% of its maximum. Grip work (GW)
      was estimated as GW=GS*0.75*FR, and compared to the measured GW. In the elderly
      participants, relationships (controlling for age and physical activity) of GS,
      FR, GW and GW corrected for body weight (GW/BW) with dependency (Katz-scale) and
      inflammation (circulating IL-6 and TNF-alpha) were analyzed. RESULTS: Excellent
      correlation between estimated and measured GW was found (r=0.98, p<0.001). The
      method error coefficient of variance was 10% for all participants; 7% for all
      elderly and 8% for young controls. Better GS, FR, GW and GW/BW was significantly
      related with less dependency (all p<0.05 or p<0.01, except for FR in the male)
      and with lower circulating IL-6 (all p<0.05 or p<0.01, except for GS in both
      genders). Higher IL-6 was significantly related to worse dependency (p<0.01). No
      significant relationships with TNF-alpha were found. CONCLUSION: GW estimation is
      a valid parameter reflecting muscle endurance in elderly persons presenting
      diverse clinical conditions. GW is significantly related to both dependency and
      circulating IL-6, and is a promising outcome parameter in comprehensive geriatric
      assessment.

PMID- 21968874
TI  - Vegetative ecological characteristics of restored reed (Phragmites australis)
      wetlands in the Yellow River Delta, China.
AB  - In this study, we compared ecological characteristics of wetland vegetation in a
      series of restoration projects that were carried out in the wetlands of Yellow
      River Delta. The investigated characteristics include plant composition
      structure, species diversity and community similarity in three kinds of
      Phragmites australis wetlands, i.e. restored P. australis wetlands (R1, R2, R3
      and R4: restored in 2002, 2005, 2007 and 2009, respectively), natural P.
      australis wetland (N) and degraded P. australis wetland (D) to assess the process
      of wetlands restoration. The coverage of the R1 was 99%, which was similar to
      natural wetland. Among all studied wetlands, the highest and lowest stem density
      was observed in R1 and R2, respectively, Plant height and stem diameter show the
      same trend as N > R2 > R1 > R3 > D > R4. Species diversity of restored P.
      australis wetlands became closed to natural wetland. Both species richness and
      Shannon-Wiener index had similar tendency: increased first and then decreased
      with restored time. The highest species richness and species diversity were
      observed in R2, while the lowest values of those parameters were found in natural
      P. australis wetland. Similarity indexes between restored wetlands and natural
      wetland increased with the restoration time, but they were still less than 50%.
      The results indicate that the vegetation of P. australis wetlands has experienced
      a great improvement after several years' restoration, and it is feasible to
      restored degraded P. australis wetlands by pouring fresh water into those
      wetlands in the Yellow River Delta. However, it is notable that costal degraded
      P. australis wetland in this region may take years to decades to reach the status
      of natural wetland.

PMID- 21968875
TI  - A bias to detail: how hand position modulates visual learning and visual memory.
AB  - In this report, we examine whether and how altered aspects of perception and
      attention near the hands affect one's learning of to-be-remembered visual
      material. We employed the contextual cuing paradigm of visual learning in two
      experiments. Participants searched for a target embedded within images of
      fractals and other complex geometrical patterns while either holding their hands
      near to or far from the stimuli. When visual features and structural patterns
      remained constant across to-be-learned images (Exp. 1), no difference emerged
      between hand postures in the observed rates of learning. However, when to-be
      learned scenes maintained structural pattern information but changed in color
      (Exp. 2), participants exhibited substantially slower rates of learning when
      holding their hands near the material. This finding shows that learning near the
      hands is impaired in situations in which common information must be abstracted
      from visually unique images, suggesting a bias toward detail-oriented processing
      near the hands.

PMID- 21968876
TI  - Biogeochemistry of mercury and methylmercury in sediment cores from Sundarban
      mangrove wetland, India--a UNESCO World Heritage Site.
AB  - This study was performed to elucidate the distribution, concentration trend and
      possible sources of total mercury (Hg(T)) and methylmercury (MeHg) in sediment
      cores (<63 MUm particle size; n = 75) of Sundarban mangrove wetland, northeastern
      part of the Bay of Bengal, India. Total mercury was determined by atomic
      absorption spectrometry (AAS) in a Leco AMA 254 instrument and MeHg by gas
      chromatography-atomic fluorescence spectrometry (GC-AFS). A wide range of
      variation in Hg(T) (0.032-0.196 MUg g(-1) dry wt.) as well as MeHg (0.04-0.13 ng
      g(-1) dry wt.) concentrations revealed a slight local contamination. The
      prevalent low Hg(T) levels in sediments could be explained by sediment transport
      by the tidal Hugli (Ganges) River that would dilute the Hg(T) values via sediment
      mixing processes. A broader variation of MeHg proportions (%) were also observed
      in samples suggesting that other environmental variables such as organic carbon
      and microbial activity may play a major role in the methylation process. An
      overall elevated concentration of Hg(T) in surface layers (0-4 cm) of the core is
      due to remobilization of mercury from deeper sediments. Based on the index of
      geoaccumulation (I (geo)) and low effects-range (ER-L) values, it is considered
      that the sediment is less polluted by Hg(T) and there is less ecotoxicological
      risk. The paper provides the first information of MeHg in sediments from this
      wetland environment and the authors strongly recommend further examination of
      Hg(T) fluxes for the development of a detailed coastal MeHg model. This could
      provide more refine estimates of a total flux into the water column.

PMID- 21968877
TI  - Stream discharge characteristics through urbanization gradient in Danshui River,
      Taiwan: perspectives from observation and simulation.
AB  - Urbanization and the subsequent changes in land use/cover inevitably influence
      the quality and even the quantity of stream water. This issue is widely studied
      through evaluations on land-use change scenarios or comparisons among historical
      patterns at the same watershed. However, observational stream discharge changes
      through urbanization gradient have rarely been discussed. In this study, we
      analyzed 5-year discharge data from 13 gauges in the Danshui River network with a
      wide range of urbanization gradient to explore the impacts on observational
      hydrological characteristics in individual catchments. The results reveal that
      stream discharge in pristine watersheds is characterized by a larger proportion
      of baseflow and is less fluctuating. When the forest coverage is <90%, the
      discharge fluctuation almost doubles. Meanwhile, the baseflow fraction decreases
      gradually with the increase of paddy area, which may concomitantly result from
      the increasing irrigation. Such a drop in baseflow may threaten the maintenance
      of the minimum flow required for the stream aquatic ecosystem. Furthermore, we
      simulated the stream discharges by TOPMODEL with blind land-use-independent
      parameters. The results show that the simulated discharges are satisfactory,
      particularly for the pristine catchments, but not as fitting for the paddy
      intensive watersheds perhaps due to the unexpected irrigation. On the whole, the
      calibrated parameters are dependent with the landscape characteristics. The
      landscape-based parameter estimations can be applied to simulate discharge well,
      meaning the potential to assess the ungauged watersheds.

PMID- 21968879
TI  - Fluorine in the rocks and sediments of volcanic areas in central Italy: total
      content, enrichment and leaching processes and a hypothesis on the vulnerability
      of the related aquifers.
AB  - Rock, sediment and water samples from areas characterised by hydrothermal
      alterations in the Sabatini and Vico Volcanic Districts, near Rome and the large
      city of Viterbo, respectively, were collected and analysed to determine the total
      fluorine (F) content and to understand the F geochemical background level in the
      volcanic districts of central Italy. Leaching and alteration processes
      controlling the high concentration of F in water were also investigated. Fluorine
      concentrations were directly determined (potentiometrically) by an F selective
      electrode in water samples, while the procedure for rock samples included
      preliminary F dissolution through alkaline fusion. F concentrations higher than
      800 mg kg(-1) were commonly found in the analysed rocks and sediments; the
      concentration depended on the lithology and on the distance from the alteration
      areas. A specific successive sampling campaign was conducted in three areas where
      the F content in sediments was particularly high; in the same areas, measurements
      of CO(2) flux were also performed to investigate the possible deep origin of F.
      To verify the relationships among the high F contents in rocks and sediments, the
      leaching processes involved and the presence of F in the aquifer, we also
      collected water samples in the western sector of the Sabatini Volcanic District,
      where hydrothermal manifestations and mineral springs are common. The data were
      processed using a GIS system in which the F distribution was combined with
      morphological and geological observations. The main results of our study are that
      (1) F concentrations are higher in volcanic and recently formed travertine
      (especially in hydrothermally altered sediments) than in sedimentary rocks and
      decrease with distance from hydrothermal alteration areas, (2) F is more easily
      leached from hydrothermally altered rocks and from travertine and (3) sediments
      enriched with F may indicate the presence of deep regional fractures that
      represent direct pathways of hydrothermal fluids from the crust to the surface.

PMID- 21968878
TI  - The dissipation of ethofenprox in cabbage and soil under open conditions.
AB  - The dissipation of ethofenprox in cabbage and soil under open conditions was
      investigated at two primary cabbage-growing regions, Beijing and Kunming in
      China. Samples were extracted with acetonitrile and determined by ultra
      performance liquid chromatography with a single quadrupole detector. Dissipation
      of ethofenprox from cabbage and soil can be best explained by a first-order decay
      process. The half-lives of ethofenprox were 1.9 and 2.3 days in cabbage and 20.0
      and 13.0 days in soil at Beijing and Kunming, respectively. The concentration of
      ethofenprox residue was reduced by 90% taking 7 and 60 days in cabbage and soil.
      Dissipation rates in cabbage and soil at two geographically separated
      experimental fields differed, suggesting that this was affected by complicated
      factors, such as local climate and soil characteristics. These data could provide
      guidance for the proper and safe use of this pesticide on cabbage in China.

PMID- 21968880
TI  - Favorable outcome in infants with AML after intensive first- and second-line
      treatment: an AML-BFM study group report.
AB  - Infants <1 year of age have a high prevalence of prognostically unfavorable
      leukemias and a presumed susceptibility to treatment-related toxicities. A total
      of 125 infants with acute myeloid leukemia (AML) were treated in studies AML-BFM
      98 (n = 59) and -2004 (n = 66). Treatment regimens of both studies were
      comparable, consisting of intensive induction followed by four courses (mainly
      high-dose cytarabine and anthracyclines). Allogeneic-hematopoietic stem-cell
      transplantation (allo-HSCT) in 1st remission was optional for high-risk (HR)
      patients. Most infants (120/125=96%) were HR patients according to morphological,
      cytogenetic/molecular genetic and response criteria. Five-year overall survival
      was 66 +/- 4%, and improved from 61 +/- 6% in study-98 to 75 +/- 6% in study-2004
      (P(logrank) 0.14) and event-free survival rates were 44 +/- 6% and 51 +/- 6%
      (P(logrank) 0.66), respectively. Results in HR infants were similar to those of
      older HR children (1-<2- or 2-<10-year olds, P(logrank) 0.90 for survival).
      Survival rates of HSCT in 1st remission, initial partial response and after
      relapse were high (13/14, 2/8 and 20/30 patients, respectively). The latter
      contributes to excellent 5-year survival after relapse (50+/-8%). Despite more
      severe infections and pulmonary toxicities in infants, treatment-related death
      rate was identical to that of older children (3%). Our data indicate that
      intensive frontline and relapse AML treatment is feasible in infants, toxicities
      are manageable, and outcome is favorable.

PMID- 21968881
TI  - AMP-dependent kinase/mammalian target of rapamycin complex 1 signaling in T-cell
      acute lymphoblastic leukemia: therapeutic implications.
AB  - The mammalian target of rapamycin (mTOR) serine/threonine kinase is the catalytic
      subunit of two multi-protein complexes, referred to as mTORC1 and mTORC2.
      Signaling downstream of mTORC1 has a critical role in leukemic cell biology by
      controlling mRNA translation of genes involved in both cell survival and
      proliferation. mTORC1 activity can be downmodulated by upregulating the liver
      kinase B1/AMP-activated protein kinase (LKB1/AMPK) pathway. Here, we have
      explored the therapeutic potential of the anti-diabetic drug, metformin (an
      LKB1/AMPK activator), against both T-cell acute lymphoblastic leukemia (T-ALL)
      cell lines and primary samples from T-ALL patients displaying mTORC1 activation.
      Metformin affected T-ALL cell viability by inducing autophagy and apoptosis.
      However, it was much less toxic against proliferating CD4(+) T-lymphocytes from
      healthy donors. Western blot analysis demonstrated dephosphorylation of mTORC1
      downstream targets. Unlike rapamycin, we found a marked inhibition of mRNA
      translation in T-ALL cells treated with metformin. Remarkably, metformin targeted
      the side population of T-ALL cell lines as well as a putative leukemia-initiating
      cell subpopulation (CD34(+)/CD7(-)/CD4(-)) in patient samples. In conclusion,
      metformin displayed a remarkable anti-leukemic activity, which emphasizes future
      development of LKB1/AMPK activators as clinical candidates for therapy in T-ALL.

PMID- 21968882
TI  - The impact of myocardial revascularization after acute coronary syndromes on one
      year cardiovascular mortality.
AB  - The aim of this observational study was to evaluate the impact of myocardial
      revascularization performed after acute coronary syndromes on one-year
      cardiovascular mortality. MATERIAL AND METHODS: The study population comprised
      1226 consecutive patients who were admitted to the Clinic of Cardiology in 2005
      because of acute coronary syndromes with significant (>=70%) coronary artery
      stenoses. The relationship between myocardial revascularization and one-year
      cardiovascular mortality was evaluated by applying multivariable logistic
      regression. Cardiovascular mortality was evaluated using the Kaplan-Meier method.
      RESULTS: Of all the patients included into the study, 540 had Q-wave myocardial
      infarction, 339 patients had non-Q-wave myocardial infarction, and 347 patients
      were treated for unstable angina pectoris. During hospitalization, 496 patients
      underwent percutaneous transluminal coronary angioplasty, 373 patients underwent
      coronary artery bypass grafting within 60 days following acute coronary
      syndromes, and 357 patients received pharmacological treatment alone. During one
      year follow-up, 105 cases of cardiovascular death were registered. The one-year
      cardiovascular mortality was significantly lower in patients who underwent
      percutaneous transluminal coronary angioplasty or coronary artery bypass grafting
      comparing with those patients who received only pharmacotherapy (5.4% and 7.8%
      vs. 14.3%, P<0.05). Multivariate logistic regression analysis revealed that
      myocardial revascularization independently reduced one-year cardiovascular
      mortality (adjusted odds ratio for percutaneous transluminal coronary
      angioplasty, 0.304; 95% CI, 0.18 to 0.53; P<0.001, and coronary artery bypass
      grafting, 0.540; 95% CI, 0.32 to 0.90; P=0.018) in patients who were admitted
      because of acute coronary syndromes. CONCLUSIONS: Myocardial revascularization
      performed after acute coronary syndromes was significantly associated with the
      reduction of cardiovascular mortality within one-year period independently of
      clinical variables.

PMID- 21968883
TI  - Executive functions in adolescents with idiopathic generalized epilepsy.
AB  - Disorders of executive functioning have recently been reported in patients with
      juvenile myoclonic epilepsy (JME); however, data on other syndromes of
      generalized idiopathic epilepsy (IGE) other than JME, especially in adolescence,
      are scarce. The aim of this study was to explore specific executive functions in
      a group of adolescents with IGE of short duration and to evaluate the possible
      factors that might influence these functions. MATERIAL AND METHODS:
      Neuropsychological investigation of executive functions (the Verbal Fluency Test,
      the Five-Point Test, the Trail-Making Test, and the Stroop test) was performed in
      59 patients aged 14-17 years and meeting the diagnostic criteria for IGE, and in
      the group of 59 age-matched controls without any history of epilepsy. RESULTS:
      The IGE group subjects scored worse than the controls in most of the executive
      function tests: phonemic (P=0.008) and semantic (P=0.001) word fluency, figural
      fluency (P=0.008), visual search and sequencing of numbers (P=0.001), and
      alternate number-letter sequencing (P=0.018). None of the test scores differed
      between the new-onset and the established IGE groups, or between the groups of
      cases with and without myoclonias. No relationship between executive functioning
      and gender, age, duration or activity of epilepsy, chronic use of treatment, or
      epileptiform discharges on electroencephalography was found. CONCLUSIONS:
      Executive dysfunction was present in adolescents with JME and other syndromes of
      IGE, manifesting with generalized tonic-clonic seizures without myoclonias,
      despite short duration and benign course of epilepsy.

PMID- 21968884
TI  - Superficial siderosis: a case report.
AB  - Superficial siderosis of the central nervous system is the result of chronic
      recurrent hemorrhages (e.g., arteriovenous malformations, tumors, or trauma),
      which leads to the accumulation of cytotoxic hemosiderin and presents with
      hearing loss, cerebellar dysfunction, and myelopathy. This article presents a
      clinical case of an 11-year-old boy in whom the diagnosis of medulloblastoma was
      established. He underwent surgery, and after a few years, he began to complain of
      hearing loss. Magnetic resonance imaging revealed the cause of the hearing
      disturbance. The aim of this article is to review the recent literature related
      to the etiology, clinical and radiologic features of superficial siderosis,
      emphasizing the role of magnetic resonance imaging.

PMID- 21968885
TI  - Comparison of long-term stability of parenteral all-in-one admixtures containing
      new lipid emulsions prepared under hospital pharmacy conditions.
AB  - All-in-one (AIO) admixtures for parenteral nutrition are common in hospital
      pharmacy practices. They are extemporaneously prepared and should be stable
      during preparation, storage, and administration. Lipid emulsion is a clinically
      important and very susceptible component of instability. The objective of study
      was to evaluate the long-term stability of AIO admixtures containing modern lipid
      emulsions. MATERIAL AND METHODS: AIO admixtures with two different emulsions
      (SMOFlipid and Lipoplus) containing the same amount of glucose and complex amino
      acid solution, and variable amounts of ions were prepared. Samples were evaluated
      at 2, 5, 8 and 30 days after preparation. The main indicator of AIO system
      stability was the amount of lipid globules greater than 5 MUm in diameter, which
      is limited by pharmacopoeia. Optical microscopy was used for particle size
      measurement. RESULTS: All prepared AIO admixtures remained stable during
      observation. The counts of overlimit lipid particles were within pharmacopeial
      limit nevertheless tended to increase in time. After 30-day storage, their value
      was influenced mainly by concentration of calcium ions, which at lower
      concentrations had a greater impact on SMOFlipid-based admixtures, whereas at the
      highest concentration on Lipoplus-based admixtures. The concentration of ions and
      osmolarity remained without changes; pH of admixtures slightly decreased.
      CONCLUSIONS: Both lipid emulsions were found to be suitable for preparation AIO
      admixtures with different concentrations of electrolytes. The formulations were
      stable even if contained high concentrations of divalent ions. The comparison of
      emulsions revealed the superiority of Lipoplus - electrolyte concentrations and
      duration of storage had a greater impact on admixtures with SMOFlipid.

PMID- 21968886
TI  - Synthesis and antimicrobial properties of naphthylamine derivatives having a
      thiazolidinone moiety.
AB  - OBJECTIVE: The aim of this study was to evaluate the influence of pharmacophores
      having naphthylamine and nitro groups on the antimicrobial (antibacterial and
      antifungal) activity of thiazolidinone derivatives. MATERIALS AND METHODS: The
      initial 5-substituted-2-methylmercaptothiazolidin-4-ones were subjected to S
      demethylation to yield 2-amino-substituted thiazolidinones. 4-Nitro-1
      naphthylamine, nitrofuran aldehydes, and nitrobenzene aldehydes were used as
      pharmacophoric compounds having amino or aldehyde groups. Antimicrobial
      (antibacterial and antifungal) activity of the new compounds was tested in vitro
      against bacterial cultures - Staphylococcus aureus, Escherichia coli, Bacillus
      subtilis, Klebsiella pneumoniae - and fungal cultures - Candida albicans, Candida
      glabrata, Candida krusei, Candida kefyr, Candida tropicalis, and Candida
      parapsilosis. RESULTS: Microbiological analysis showed that all new
      thiazolidinone derivatives with nitronaphthylamine substituent possessed
      antibacterial and antifungal properties. New compounds 2a-b showed similar
      antibacterial activity in vitro against S. aureus and B. subtilis as
      aminopenicillins. The lowest antibacterial activity of all newly synthesized
      compounds was against capsule-forming bacteria K. pneumoniae and against gram
      negative bacteria E. coli (minimum inhibitory concentration range, 500-1000
      MUg/mL). CONCLUSIONS: The minimum inhibitory concentration of naphthylamine
      derivatives varied in the range of 0.4-1000 MUg/mL, and activity of some newly
      synthesized compounds was similar to the activity of aminopenicillins and
      fluconazole, an antifungal preparation. Based on the results, it is possible to
      separate the perspective group of potential antimicrobial compounds.

PMID- 21968887
TI  - The prevalence of problem drug use in lithuania.
AB  - The aim of this study was to estimate and assess the prevalence of problem drug
      use in Lithuania. MATERIALS AND METHODS: The capture-recapture method was used to
      estimate the prevalence of problem drug use. For the study, the data concerning
      problem drug users were collected from the databases of health care and law
      enforcement institutions. The target group consisted of permanent users (aged 15
      64 years) of heroin and other opioids and/or a combination of drugs. RESULTS: In
      Lithuania, 431 monitored problem drug users were identified in 2005, 482 in 2006,
      and 447 in 2007. The male-to-female ratio among the monitored problem drug users
      was 6:1 in 2006 and 4:1 in 2005 and 2007. The mean age of the monitored problem
      drug users was 26.8 years in 2005, 27.6 years in 2006, and 28.0 years in 2007. In
      total, 5699 problem drug users were identified (95% CI, 5552 to 5849) in 2005,
      5800 (95% CI, 5652 to 5951) in 2006, and 5458 (95% CI, 5314 to 5605) in 2007.
      According to the gathered data, the prevalence of problem drug use was 2.3 cases
      per 1000 Lithuanian population aged 15-64 years in 2005, 2.5 in 2006, and 2.4 in
      2007. CONCLUSIONS: The study showed one of the lowest prevalence of problem drug
      use in Lithuania as in Germany, the Netherlands, Greece, and Cyprus. In 2005
      2007, problem drug users were mainly young men of employable age in Lithuania.

PMID- 21968888
TI  - Inequalities in mortality from infectious diseases and tuberculosis by the level
      of education in Lithuania.
AB  - The aim of this study was to evaluate changes in inequalities in mortality from
      infectious diseases and tuberculosis by educational level among men and women in
      Lithuania. MATERIAL AND METHODS: The data on mortality from infectious diseases
      in the Lithuanian population aged more than 30 years for the years 1989 and 2001
      gathered from the Department of Statistics and censuses were used for the
      analysis. The relative and slope indices of inequality were calculated. RESULTS:
      Mortality from infectious diseases and tuberculosis among persons with primary
      education was higher than that among persons with university education, and these
      inequalities were found to be increased in 2000-2002 as compare with 1988-1990
      due to declining mortality among persons with university education and increasing
      mortality among less educated persons. Similar tendencies were observed while
      evaluating the inequalities in mortality from tuberculosis. In 1988- 1990, the
      relative indices of inequality for mortality from all infectious diseases and
      tuberculosis among men were 9 and 13, respectively. In 2000-2002, the relative
      indices of inequality increased significantly to 16.5 and 28.8, respectively.
      Inequalities in mortality from abovementioned causes for women with different
      educational levels were lower than those for men. The slope indices of inequality
      for mortality from infectious diseases among men with different educational
      levels were considerably higher than among their female counterparts, and in 2000
      2002, they were greater compared with 1988-1990. CONCLUSIONS: While implementing
      tuberculosis prevention and control program and planning prevention and control
      measures, greater attention should be paid to less educated Lithuanian population
      at highest risk of this disease.

PMID- 21968889
TI  - [A study on release of propolis extract components from emulsion-type
      dispersions].
AB  - BACKGROUND AND OBJECTIVE: Carrier development is one of the essential stages in
      the formulation of semisolid pharmaceutical dosage form for topical application.
      The stability of semisolid preparation during storage can be predicted from
      rheological testing. An adequate composition of semisolid preparation determines
      its stability and proper release of drug substance, and allows bypassing long
      term heating and melting of the cream base components while incorporating complex
      extracts. Soft propolis extract, well known for its antimicrobial, antiviral,
      anti-inflammatory, and antioxidant effects, was chosen as a complex biologically
      active ingredient for the development of emulsion dispersion system. The aim of
      this study was to evaluate the impact of physical-chemical characteristics of the
      carrier on the release rate of biologically active ingredients from the modeled
      dosage form in vitro, thus justifying the relevance of the carrier composition
      and applied technologies. MATERIAL AND METHODS: Soft propolis extract (1%-3%) was
      incorporated into water-in-oil type emulsion. The quality of the model systems
      was evaluated referring to their viscosity, quantity of polyphenols and their
      rate of release from the preparation by applying an in vitro model. Quantitative
      determination of polyphenols was performed by spectrophotometry using a standard
      calibration curve of ferulic acid. RESULTS: The results showed that a stable
      homogeneous semisolid emulsion system containing soft propolis extract could be
      produced when the concentration of emulsifier was in the range of 3%-12%. The
      quantity of emulsifier had an impact on the viscosity of semisolid systems, but
      practically had no effect on the release rate of polyphenols from the cream
      matrix. The results also demonstrated that the added amount of soft propolis
      extract had a less significant effect than temperature of the system. CONCLUSION:
      It was confirmed that changes in the viscosity of emulsion dispersion systems had
      no effect on the stability of model dispersion systems when temperature was
      increased, and this has to be evaluated to determine the storage conditions of
      the model preparations.

PMID- 21968890
TI  - Large-scale network models of IL-1 and IL-6 signalling and their hepatocellular
      specification.
AB  - The pro-inflammatory cytokines interleukin 1 (IL-1) and 6 (IL-6) are crucially
      involved in the regulation of a multitude of physiological processes, in
      particular coordinating the immune response upon bacterial infection and tissue
      injury. Both interleukins induce complex signalling cascades and trigger the
      production of mitogenic, pro-proliferative, anti-apoptotic, chemotactic, and pro
      angiogenic factors thereby affecting the delicate balance between regeneration
      vs. invasive growth, tumourigenesis and metastasis. Moreover, several links to
      insulin resistance have been found within their associated signalling networks.
      Focusing on this from a systems biology perspective, we introduce comprehensive
      large-scale network models of IL-1 and IL-6 signalling which are based on a
      logical modelling approach and reflect the current biological knowledge.
      Theoretical network analysis enabled us to uncover general topological features
      and to make testable predictions on the stimulus-response behaviour of the
      networks. In this context, non-intuitive network-wide species dependencies as
      well as structures of regulatory feedback and feed-forward mechanisms could be
      characterised. By integrating high-throughput phosphoproteomic data from primary
      human hepatocytes we optimised the model structures to obtain models with high
      prediction accuracy for hepatocytes. Our model-based data analysis, for instance,
      suggested model modifications regarding (i) Akt contribution to IL-1-stimulated
      p38 MAPK activation and (ii) insignificant p38 MAPK activation in response to IL
      6. In light of the presented results and in conjunction with the detailed model
      documentations, both models hold great potential for theoretical studies and
      practical applications.

PMID- 21968891
TI  - Ab initio characterization of size dependence of electronic spectra for linear
      anionic carbon clusters C(n) (-)  (n = 4-17).
AB  - In this article, we determine the ground-state equilibrium geometries of the
      linear anionic carbon clusters C n- (n = 4-17) by means of the density functional
      theory B3LYP, CAM-B3LYP, and coupled cluster CCSD(T) calculations, as well as
      their electronic spectra obtained by the multireference second-order perturbation
      theory CASPT2 method. These studies indicate that these linear anions possess
      doublet 2?(g) or 2?(u) ground state, and the even-numbered clusters are generally
      acetylenic, whereas the odd-numbered ones are essentially cumulenic. The energy
      differences, electron affinities, and incremental binding energies of C n- chains
      all exhibit a notable tread of parity alternation, with n-even chains being more
      stable than n-odd ones. In addition, the predicted vertical excitation energies
      from the ground state to four low-lying excited states are in reasonably good
      agreement with the available experimental observations, and the calculations for
      the higher excited electronic transitions can provide accurate information for
      the experimentalists and spectroscopists. Interestingly, the absorption
      wavelengths of the 12?(u/g) <- X2?(g/u) transitions of the n-even clusters show a
      nonlinear trend of exponential growth, whereas those of the n-odd counterparts
      are found to obey a linear relationship as a function of the chain size, as shown
      experimentally. Moreover, the absorption wavelengths of the transitions to the
      higher excited states of C n- series have the similar linear size dependence as
      well.

PMID- 21968892
TI  - [The incidence of human papilloma virus associated vulvar cancer in younger women
      is increasing and wide local excision with sentinel lymph node biopsie has become
      standard].
AB  - PURPOSE OF REVIEW: Sentinel lymph node (SLN) dissections have been shown to be
      sensitive for the evaluation of nodal basins for metastatic disease and are
      associated with decreased short-term and long-term morbidity when compared with
      complete lymph node dissection. There has been increasing interest in the use of
      SLN technology in gynecologic cancers. This review assesses the current evidence
      based literature for the use of SLN dissections in gynecologic malignancies.
      RECENT FINDINGS: Recent literature continues to support the safety and
      feasibility of SLN biopsy for early stage vulvar cancer with negative predictive
      value approaching 100 % and low false negative rates. Alternatively, for
      endometrial cancer most studies have reported low false-negative rates, with
      variable sensitivities and have reported low detection rates of the sentinel
      node. Studies examining the utility of SLN biopsy in early-stage cervical cancer
      remain promising with detection rates, sensitivities, and false-negative rates
      greater than 90 % for stage 1B1 tumors. SUMMARY: SLN dissections have been shown
      to be effective and safe in certain, select vulvar cancer patients and can be
      considered an alternative surgical approach for these patients. For endometrial
      and cervical cancer, SLN dissection continues to have encouraging results and
      however needs further investigation.

PMID- 21968893
TI  - [Cervical cancer].
AB  - Cervical cancer is the third most common malignancy in women and a major cause of
      morbidity and mortality particularly in developing countries. In Switzerland
      cervical cancer is nowadays a relative rare cancer with annually 230 new cases.
      Decreasing incidence, observed in all age groups, is certainly due to improved
      primary and secondary prevention such as comprehensive screening programs and in
      future with vaccination against human papilloma viruses. Improvements in the
      treatment of cervical cancer led to a reduction of mortality. This review article
      summarizes the current standard of care with and the available treatment
      modalities.

PMID- 21968894
TI  - [Endometrial cancer - state of the art].
AB  - Endometrial cancer is the most common genital malignant tumor in women in
      industrial countries. The typical symptoms are postmenopausal bleeding or
      metrorrhagia. Following anamneses, clinical examination and transvaginal
      sonography, histological confirmation is obtained by dilation and curettage.
      Hysterectomy, bilateral salpingo-oophorectomy and according to tumor stage pelvic
      and paraaortic lymphadenectomy are the mainstay of surgical treatment that is
      performed more and more often by laparoscopy. Adjuvant pelvic external beam
      radiation or vaginal brachytherapie are added if indicated. In certain situations
      adjuvant chemotherapy is necessary. Follow-up by clinical examination and
      transvaginal sonography are reasonable for the first few postoperative years.

PMID- 21968895
TI  - [Sarcomas and mixed mesodermal tumors of the uterus].
AB  - Malignant mesodermal tumors of the uterus are an inhomogenous group of uterine
      malignancies with different pathogenesis, clinical presentation and prognosis.
      These rare tumors represent approximately 1 % of all uterine malignancies. The
      aggressive carcinosarcomas or mixed muellerian tumors are defined by mixed
      malignant epithelial and malignant mesodermal histopathology and are of the same
      precursor cell origin like endometrial cancer. Thus, carcinosarcomas were
      reclassified by the FIGO as an aggressive type of endometrial cancer and treated
      like type II endometrial cancer. Adenosarcomas are also mixed tumors with benign
      epithelial proliferation and malignant mesodermal cell growth, have a good
      prognosis and represent less than 5 % of all mesodermal uterine malignancies.
      Besides carcinosarcomas, the pure mesodermal leiomyosarcomas are the most common
      mesodermal malignancies. Patients with leiomyosarcamos are usually
      perimenopausal, and although more than half of the patients present with
      symptoms, diagnosis occurs incidentally in most cases in final histopathologic
      workup of an excised putative myoma or uterus. Adequate anamnesis, gynecologic
      examination and careful imaging by transvaginal ultrasound in the preoperative
      setting might hint to correct differential diagnosis in many cases. Overall the
      prognosis of uterine leiomyomas is poor. Malignancies of the endometrial stroma
      are very rare and divided in two subgroups, the mostly estrogen receptor positive
      endometrial stromal sarcoma, which occur preferably in premenopausal women and
      show a favorable prognosis, and the very aggressive undifferentiated endometrial
      sarcomas. The more rare undifferentiated endometrial sarcomas occur in
      postmenopausal women and most patients die in the first two years after
      diagnosis. Risk stratification of preoperative differential diagnosis requires
      improvements and the correct histopathologic workup of mesodermal uterine
      malignancies is still a challenge for pathologists.

PMID- 21968896
TI  - [Epithelial ovarian cancer - a change of paradigm].
AB  - Epithelial ovarian cancer has the highest mortality rate within gynecological
      cancers as early symptoms are vague and unspecific and two-thirds of patients are
      presenting with advanced stage disease. Due to the innovative findings of proteo
      genomic studies during the last decade a change in paradigm has occurred. Ovarian
      cancer, which so far was assumed to be one disease deriving from a single layer
      of ovarian surface epithelial cells, has now become known to be heterogeneous and
      genetically distinct from each other, possibly even deriving from different parts
      of the female genital system. Our continuously increasing knowledge has made us
      aware that diagnosis and therapy has to target the molecular pathway more than
      the organ of origin. This will impact on ovarian cancer and will make it more and
      more controllable during the next ten years.

PMID- 21968897
TI  - [Fertility preservation and pregnancy in gynecological cancers].
AB  - Fertility preservation and pregnancy in gynecologic cancers are becoming more
      important since women delay childbearing and progress in medicine has a positive
      impact on survival of patients. The standard therapy in case of cancers of the
      endometrium, cervix and ovaries is a hysterectomy and a bilateral adnexectomy. If
      patients want to preserve fertility the standard procedure can be changed in well
      selected cases. In early stages of endometrial cancer progesterone therapy, in
      cervical cancer conisation or trachelectomy, and in ovarian cancer a fertility
      sparing operation can be offered. Nowadays a therapy option can be offered to all
      pregnant patients diagnosed with cancer - depending on the gestational age, the
      tumor type, tumor stage and the expectation of the future mother.

PMID- 21968898
TI  - [Gynecological cancer and sexuality].
AB  - Sexual problems and dysfunction after gynecological cancer is frequent, however
      is still too seldom systematically addressed during consultation. Surgery and
      adjuvant radiotherapy (external/brachytherapy) and chemotherapy damage neuronal
      structures and the vaginal tissue and in the case of removal of the ovaries or
      impairing their function are associated with endocrine changes which impact
      sexuality. The patient and her partner are challenged to adjust their sexual
      repertoire to these changes. The success of this adaptation process is partly
      dependent on individual and relationship factors. The treatment of sexual
      dysfunction after gynecological cancer includes body oriented (use of dilators,
      pelvic floor exercises) and pharmacological interventions (a.o. local estrogens,
      lubricants) and counseling of the patient and the couple.

PMID- 21968899
TI  - Aseptic loosening rates in distal femoral endoprostheses: does stem size matter?
AB  - BACKGROUND: Long-term survival of distal femoral endoprosthetic replacements is
      largely affected by aseptic loosening. It is unclear whether and to what degree
      surgical technique and component selection influence the risk of loosening.
      QUESTIONS/PURPOSES: We (1) established the overall failure and aseptic loosening
      rates in a tumor population and asked (2) whether stem diameter and specifically
      the diaphysis-to-stem ratio predicts loosening, and (3) whether resection
      percentage correlates with failure. METHODS: We retrospectively reviewed the
      charts of all 93 patients in whom 104 distal femoral replacements had been
      performed from 1985 to 2008. We extracted the following data: age, need for
      revision surgeries, tumor diagnosis, adjunct treatment, and implant
      characteristics. We reviewed radiographs and determined stem size, bone
      diaphyseal width, and resection percentage of the femur. Kaplan-Meier
      survivorship was calculated for all implant failures and failures resulting from
      aseptic loosening. We evaluated radiolucent lines in patients with radiographic
      followup over 5 years. We identified independent risk factors for loosening. The
      minimum followup for radiographic evaluation was 5 years (mean, 12.7 years;
      range, 5.4-23.5 years). RESULTS: Overall implant survival for 104 stems in 93
      patients was 73.3% at 10 years, 62.8% at 15 years, and 46.1% at 20 years.
      Survival from aseptic loosening was 94.6% at 10 and 15 years and 86.5% at 20
      years. Of the variables analyzed, only bone:stem ratio independently predicted
      aseptic failure. Patients with stable implants had larger stem sizes and lower
      bone:stem ratios than those with loose implants (14.5 mm versus 10.7 mm and 2.02
      versus 2.81, respectively). CONCLUSIONS: Our data suggest durability relates to
      selecting stems that fill the canal. LEVEL OF EVIDENCE: Level III, therapeutic
      study. See Guidelines for Authors for a complete description of levels of
      evidence.

PMID- 21968900
TI  - Incidence of contralateral THA after index THA for osteoarthritis.
AB  - BACKGROUND: Currently more than 200,000 THAs are performed annually in the United
      States. In patients with bilateral disease, the chance of subsequent
      contralateral THA reportedly ranges from 16% to 85%. Factors influencing
      contralateral THA are not completely understood. QUESTIONS/PURPOSES: We therefore
      determined (1) the 10-year probability free of progression to contralateral THA
      after index THA, (2) whether demographics differed between those who did and did
      not ultimately undergo contralateral THA, and (3) whether initial clinical
      symptoms and/or degree of radiographic osteoarthritis affects progression.
      PATIENTS AND METHODS: We retrospectively identified 332 patients with minimum 24
      month followup and primary osteoarthritis who underwent unilateral THA between
      2001 and 2008. There were 150 men and 182 women with a mean age of 61 years
      (range, 27-93 years) and a mean BMI of 29.6 kg/m(2) (range, 17.6-49.2 kg/m(2)).
      We reviewed clinical, radiographic, and demographic data at index THA and last
      followup and classified patients as low, indeterminate, or high risk of
      undergoing contralateral THA. RESULTS: Seventy-four of the 332 patients (22%)
      underwent contralateral THA, resulting in an 83% 10-year probability free of
      progression to the contralateral hip. Low-risk patients had a less than 1% chance
      of progression, indeterminate-risk patients had a 16% to 24% chance of
      progression, and high-risk patients had a 97% chance of progression. CONCLUSIONS:
      Indeterminate-risk patients may be managed nonoperatively and deserve further
      study with a larger multicenter analysis. We defined high- and low-risk patients
      who may be candidates for bilateral THA or may rarely need a contralateral THA.
      LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a
      complete description of levels of evidence.

PMID- 21968901
TI  - Are bone and serum cefazolin concentrations adequate for antimicrobial
      prophylaxis?
AB  - BACKGROUND: Antimicrobial prophylaxis is considered beneficial for preventing
      surgical-site infections in clean orthopaedic surgery. However, whether tissue
      concentrations of cefazolin achieve the minimum inhibitory concentration for the
      targeted contaminants have yet to be clarified. QUESTIONS/PURPOSES: We asked
      whether 2 g of cefazolin would enable effective serum and bone concentrations
      relative to the current minimum inhibitory concentration for cefazolin-resistant
      coagulase-negative Staphylococci and methicillin-sensitive Staphylococcus aureus.
      PATIENTS AND METHODS: We enrolled 43 patients (THA, n = 16; TKA, n = 27)
      scheduled for primary THAs and primary TKAs. Subjects were given 2 g of cefazolin
      intravenously before incision. One blood sample and two bone samples were
      collected from each subject before tourniquet deflation before any additional
      dose. All samples were assayed at the same laboratory. Minimum inhibitory
      concentration values were defined based on nationwide surveys. RESULTS: Mean (+/-
      standard deviation) serum concentration was 170.3 +/- 51.3 MUg/mL (range, 99.3
      370.3 MUg/mL). Mean bone concentration was 32.3 +/- 15.2 MUg/g (range, 11.4-70.0
      MUg/g) in THA, and 16.0 +/- 10.4 MUg/g (range, 6.3-46.3 MUg/g) in TKA. All serum
      and bone concentrations exceeded the minimum inhibitory concentration for
      methicillin-sensitive S. aureus, but some serum levels were marginal and no bone
      levels exceeded the minimum inhibitory concentration for cefazolin-resistant
      coagulase-negative Staphylococcus. CONCLUSIONS: Our data suggest intravenous
      administration of 2 g of cefazolin achieves the minimum inhibitory concentration
      for methicillin-sensitive S. aureus in serum and bone, but not the minimum
      inhibitory concentration for cefazolin-resistant coagulase-negative
      Staphylococcus in bone, resulting in a potential risk of deep surgical site
      infections in THAs and TKAs.

PMID- 21968902
TI  - Methylxanthine inhibit fungal chitinases and exhibit antifungal activity.
AB  - Chitinases are necessary for fungal cell wall remodeling and cell replication.
      Methylxanthines have been shown to competitively inhibit family 18 chitinases in
      vitro. We sought to determine the effects of methylxanthines on fungal
      chitinases. Fungi demonstrated variable chitinase activity and incubation with
      methylxanthines (0.5-10 mM) resulted in a dose-dependent decrease in this
      activity. All fungi tested, except for Candida spp., demonstrated growth
      inhibition in the presence of methylxanthines at a concentration of 10 mM. India
      ink staining demonstrated impaired budding and decreased cell size for
      methylxanthine-treated Cryptococcus neoformans. C. neoformans and Aspergillus
      fumigatus treated with pentoxifylline also exhibited abnormal cell morphology. In
      addition, pentoxifylline-treated C. neoformans exhibited increased susceptibility
      to calcofluor and a leaky melanin phenotype consistent with defective cell wall
      function. Our data suggest that a variety of fungi express chitinases and that
      methylxanthines have antifungal properties related to their inhibition of fungal
      chitinases. Our results highlight the potential utility of targeting chitinases
      in the development of novel antifungal therapies.

PMID- 21968903
TI  - T cell protein tyrosine phosphatase deficiency results in spontaneous synovitis
      and subchondral bone resorption in mice.
AB  - OBJECTIVE: T cell protein tyrosine phosphatase (TC-PTP) is an important regulator
      of hematopoiesis and cytokine signaling. Recently, several genome-wide
      association studies have identified single-nucleotide polymorphisms (SNPs) in the
      locus of TC-PTP that are associated with rheumatoid arthritis and juvenile
      idiopathic arthritis, among other autoimmune diseases. The aim of this study was
      to evaluate the effect of TC-PTP deficiency on the bone and joint environment
      using a knockout mouse model. METHODS: Radiographic and micro-computed tomography
      analyses were performed on femurs of 3-week-old mice. In addition, the
      femorotibial joints were assessed by histology, flow cytometry, and cytokine
      detection. RESULTS: Deficiency of TC-PTP resulted in decreased bone volume as
      well as an increase in osteoclast density within the mouse femurs. In addition,
      synovitis, characterized by infiltration of mixed inflammatory cell types and
      proinflammatory cytokines, developed in the knee joints of TC-PTP(-/-)  mice.
      CONCLUSION: These findings demonstrate that loss of TC-PTP expression results in
      synovitis with several hallmarks of inflammatory arthritis. The inflammatory
      environment observed in the knee joints of TC-PTP(-/-)  mice differs from the
      systemic inflammation previously described in these mice and merits further
      research into the role of TC-PTP in the synovium. Furthermore, the results
      support recently described associations between SNPs in the TC-PTP locus and
      arthritis incidence.

PMID- 21968904
TI  - A possible degree of motional freedom in bacterial chemoreceptor cytoplasmic
      domains and its potential role in signal transduction.
AB  - We describe an array of gaps in an antiparallel four-helix bundle structure, the
      cytoplasmic domains of bacterial chemoreceptors. For a given helix, the side
      chain interactions that define a helix's position are analyzed in terms of
      residue interfaces, the most important of which are a-a, g-g, d-d, g-d, and a-d.
      It was found that the interdigitation of the side groups does not entirely fill
      the space along the long axis of the structure, which results in a rather regular
      array of gaps. A simulated piston motion of helix CD1 along the helical axis
      direction by 1.2A shows that 85% of the side chain interactions still satisfy Van
      der Waals criteria, while the remaining clashes could be avoided by small
      rotations of side chains. Therefore, two states could exist in the structure,
      related by a piston motion. Analysis of the crystal structure of a small four
      helix bundle, the P1(short) domain of CheA in Thermotoga Maritima, reveals that
      the two coexisting states related by a 1.3-1.7A piston motion are defined by the
      same mechanism. This two-state model is a plausible candidate mechanism for the
      long distance signal transduction in bacterial chemoreceptors and is
      qualitatively consistent with literature chemoreceptor mutagenesis results. Such
      a mechanism could exist in many other structures with interdigitating alpha
      helices.

PMID- 21968905
TI  - Overweight children with type 1 diabetes have a more favourable lipid profile
      than overweight non-diabetic children.
AB  - In the present article, we aimed to compare the cardiometabolic risk between
      overweight children with and without type 1 diabetes (T1DM). Therefore, data with
      regard to cardiometabolic risk parameters of 44 overweight Caucasian children (3
      18 years) with T1DM were matched with 44 overweight peers without T1DM for sex,
      ethnicity, age and standard deviation score of BMI (Z-BMI). Detailed history was
      taken, information regarding anthropometrics and family history were collected
      and blood pressure was measured. Blood samples were collected for evaluation of
      lipid profiles (fasting in controls, non-fasting in T1DM children), alanine
      aminotransferase and HbA1c (in children with T1DM). It was found that overweight
      children with T1DM had lower median standard deviation score of waist
      circumference (Z-WC) as compared to the overweight control group [median, 2.0
      (interquartile range, IQR, 1.5-2.3) vs. 2.6 (IQR, 2.0-2.9), P < 0.001]. After
      adjustment for Z-WC, in children with T1DM, median high-density lipoprotein
      cholesterol levels were significantly higher and median low-density lipoprotein
      cholesterol lower in T1DM children, as compared to their peers without T1DM [1.40
      (IQR, 1.2-1.5) vs. 1.2 (IQR, 1.0-1.3) and 2.7 (IQR, 2.5-3.2) vs. 3.0 (IQR, 2.5
      3.4), respectively, all P < 0.01]. When dividing children according to glycaemic
      status, children with suboptimal glycaemic control had higher values of
      triglycerides as compared to well-controlled children [1.3 (IQR, 1.0-1.8) vs.
      0.96 (IQR, 0.80-1.2), P = 0.036]. In conclusion, overweight children with T1DM
      have a more favourable lipid profile, as compared to non-diabetic overweight
      controls, in spite of a higher frequency of a positive family history of CVD,
      T2DM and hypertension. Still, paediatricians should give extra attention to
      cardiometabolic risk factors within this vulnerable group, taking into account
      the already high cardiometabolic risk.

PMID- 21968906
TI  - Educational paper : retinal haemorrhages in abusive head trauma in children.
AB  - Retinal haemorrhages are an important component of the clinical effects of non
      accidental head injuries which have significant visual morbidity. Their
      importance extends into the legal investigations of carers of children with
      subdural haemorrhages and encephalopathy who are suspected of having been non
      accidentally injured. The vital precision in diagnosis relies not just on the
      presence of retinal haemorrhages but on the severity, extent, bilaterality and
      their location in the retina. Inadequate documentation of ophthalmological
      clinical findings and too short a follow-up to allow proper assessment of
      severity each give rise to difficulties for both expert witnesses and the courts.

PMID- 21968907
TI  - Educational paper: Defects in number and function of neutrophilic granulocytes
      causing primary immunodeficiency.
AB  - The neutrophilic granulocyte (neutrophil) is the most important cellular
      component of the innate immune system. A total absence of neutrophils or a
      significant decrease in their number leads to severe immunodeficiency. A mature
      neutrophil, released from the bone marrow, should be able to migrate from the
      blood towards the tissues, following a chemotactic gradient to a pathogen. In
      order to be neutralized, this pathogen has to be recognized, phagocytosed, and
      destroyed by lytic enzymes contained in the neutrophil's granules and reactive
      oxygen species formed by the enzyme complex NADPH oxidase. Rare genetic defects
      leading to the loss of each one of these biological properties of the neutrophil
      have been described and are associated with immunodeficiency. This review
      provides a summary of the normal development and biological functions of
      neutrophils and describes the diseases caused by defects in neutrophil number and
      function.

PMID- 21968908
TI  - Quantitative buffy coat (QBC) test for rapid diagnosis of malaria.

PMID- 21968909
TI  - Empty colon: a pitfall in the assessment of colonic transit time.
AB  - We report a misleading outcome of colonic transit time (CTT) assessment in an
      adolescent girl with functional constipation. We found prolonged total and right
      segmental CTT despite high doses of oral polyethylene glycol 4000 and repeated
      treatment with polyethylene glycol-electrolyte solution (Klean-Prep(r)) by
      nasogastric tube. A colonoscopy aiming at disimpaction of a possible faecal mass
      revealed an empty colon with dozens of radio-opaque markers adhered to the
      colonic wall. This report shows that the result of a CTT cannot be accepted
      blindly. Especially the clustering of many markers within narrow margins might
      point at entrapment of markers in mucus against the colonic wall.

PMID- 21968910
TI  - Computing gene expression data with a knowledge-based gene clustering approach.
AB  - Computational analysis methods for gene expression data gathered in microarray
      experiments can be used to identify the functions of previously unstudied genes.
      While obtaining the expression data is not a difficult task, interpreting and
      extracting the information from the datasets is challenging. In this study, a
      knowledge-based approach which identifies and saves important functional genes
      before filtering based on variability and fold change differences was utilized to
      study light regulation. Two clustering methods were used to cluster the filtered
      datasets, and clusters containing a key light regulatory gene were located. The
      common genes to both of these clusters were identified, and the genes in the
      common cluster were ranked based on their coexpression to the key gene. This
      process was repeated for 11 key genes in 3 treatment combinations. The initial
      filtering method reduced the dataset size from 22,814 probes to an average of
      1134 genes, and the resulting common cluster lists contained an average of only
      14 genes. These common cluster lists scored higher gene enrichment scores than
      two individual clustering methods. In addition, the filtering method increased
      the proportion of light responsive genes in the dataset from 1.8% to 15.2%, and
      the cluster lists increased this proportion to 18.4%. The relatively short length
      of these common cluster lists compared to gene groups generated through typical
      clustering methods or coexpression networks narrows the search for novel
      functional genes while increasing the likelihood that they are biologically
      relevant.

PMID- 21968911
TI  - Long-term outcomes of three-dimensional conformal radiation therapy combined with
      neoadjuvant hormonal therapy for Japanese patients with T1c-T2N0M0 prostate
      cancer.
AB  - BACKGROUND: The outcomes of three-dimensional conformal radiation therapy (3D
      CRT) combined with neoadjuvant hormonal therapy (NAHT) in Japanese patients with
      T1c-T2N0M0 prostate cancer, with initiation of salvage hormonal therapy (SHT) at
      a relatively early phase, were analyzed. METHODS: Fifty-nine Japanese patients
      with T1c-T2N0M0 prostate cancer who received radical 3D-CRT between January 1999
      and January 2003 were evaluated. The median age, initial prostate-specific
      antigen (PSA) level, and duration of NAHT were: 72 years, 9.4 ng/ml, and 6
      months, respectively. Seventy Gy was given in 35 fractions confined to the
      prostate +/- seminal vesicles. AHT was not administered after 3D-CRT in any
      patients. RESULTS: The median follow-up period was 89 months. The median PSA
      value at the time of initiation of SHT was 4.7 ng/ml (range 0.1-21.6 ng/ml). The
      overall, disease-specific, PSA failure-free (based on the Phoenix definition),
      and SHT-free survival rates at 8 years were 82.8% (95% confidence interval [CI]
      72.4-93.2), 100%, 62.4% (47.1-77.8), and 82.6% (71.3-94.0), respectively. Only
      one patient developed grade 3 late toxicity. CONCLUSIONS: The PSA control rates
      in our series of Japanese patients with stage T1c-T2N0M0 prostate cancer treated
      with the standard dose of 3D-CRT combined with NAHT seemed at least comparable to
      those reported from Western countries; as well, the patients had excellent
      outcomes. The present outcomes can be used as basic data for evaluating the
      impact of dose escalation with intensity-modulated radiation therapy for Japanese
      patients with prostate cancer in the future.

PMID- 21968913
TI  - Mono- and dinuclear Ru(II) complexes of 1,4-bis(3-(2-pyridyl)pyrazol-1
      ylmethyl)benzene): synthesis, structure, photophysical properties and
      electrochemiluminescent determination of diuretic furosemide.
AB  - Mononuclear ruthenium complex 1 and dinuclear complex 2 were synthesized by
      reaction of the appropriate bidentate pyrazolyl-pyridyl-based ligand L (L = 1,4
      bis(3-(2-pyridyl)pyrazol-1-ylmethyl)benzene) with cis-Ru(bipy)(2)Cl(2).2H(2)O.
      They were characterized by elemental analyses, ESI-MS, (1)H spectroscopy, and X
      ray crystallography for 2. Compounds 1 and 2 both emit strongly in solid states
      and in solutions at 298 K with the lifetimes in the microsecond range.
      Electrogenerated chemiluminescence (ECL) of complexes 1 and 2 in the absence or
      presence of coreactant tri-n-propylamine (TPrA) or 2-(dibutylamino)ethanol (DBAE)
      at different working electrodes in acetonitrile and phosphate buffer solutions
      (PBS, pH 7.5) was studied. The ECL spectra are identical to the photoluminescence
      spectra, indicating that the ECL emissions are due to the metal to ligand charge
      transfer (MLCT). In all cases, ECL quantum efficiencies of dinuclear complex 2
      are higher than those of mononuclear complex 1, and ECL quantum efficiencies of
      complexes 1 and 2/TPrA system are higher than those of DBAE system. It is noted
      that diuretic furosemide tends to decrease the ECL intensity of complex 2/TPrA
      system in PBS (pH 7.5) at GC working electrode. A novel ECL method for the
      determination of diuretic furosemide was developed with a linear range between
      2.0 * 10(-7) mol L(-1) and 1.0 * 10(-6) mol L(-1), and a detection limit of 1.2 *
      10(-8) mol L(-1) based on 3 times the ratio of signal-to-noise.

PMID- 21968912
TI  - Serum total oxidant/antioxidant status and trace element levels in breast cancer
      patients.
AB  - BACKGROUND: Oxidative stress and trace elements have been implicated in the
      development of breast cancer. However, how they contribute to the pathogenesis of
      the disease and the relationship between them remain unclear. In addition, most
      previous studies detecting one or a few oxidant/antioxidant markers failed to
      consider the overall oxidant/antioxidant status of the subjects. This study was
      designed to address this and to investigate the association between oxidative
      status and trace elements in the pathogenesis of breast cancer. METHODS: Fifty
      six patients with breast carcinoma at different clinical stages, 32 patients with
      benign breast tumor, and 20 healthy subjects (controls) were recruited into this
      study. Their serum total antioxidant status (TAS), total oxidant status (TOS),
      oxidative stress index (OSI), and levels of Cu, Zn, Fe, Se, Mg, and Mn were
      measured. RESULTS: Levels of TAS, TOS, OSI, and trace elements significantly
      differed between the study groups. Among subgroups of patients with different
      clinical stages of breast cancer, the levels of all the trace elements except Zn
      were similar, whereas TAS, TOS, and OSI levels were all significantly different.
      There were significant correlations between oxidative stress parameters and
      levels of trace elements in patients with breast carcinoma but not in patients
      with benign breast tumor or in the healthy controls. CONCLUSIONS: Disturbed
      oxidative stress status and trace element levels may contribute to the
      pathogenesis of breast tumors. TAS, TOS, and OSI may be useful biomarkers for
      monitoring the clinical status of breast cancer.

PMID- 21968915
TI  - Locality-Sensitive Hashing for Chi2 distance.
AB  - In the past 10 years, new powerful algorithms based on efficient data structures
      have been proposed to solve the problem of Nearest Neighbors search (or
      Approximate Nearest Neighbors search). If the Euclidean Locality Sensitive
      Hashing algorithm, which provides approximate nearest neighbors in a euclidean
      space with sublinear complexity, is probably the most popular, the euclidean
      metric does not always provide as accurate and as relevant results when
      considering similarity measure as the Earth-Mover Distance and 2 distances. In
      this paper, we present a new LSH scheme adapted to 2 distance for approximate
      nearest neighbors search in high-dimensional spaces. We define the specific
      hashing functions, we prove their local-sensitivity, and compare, through
      experiments, our method with the Euclidean Locality Sensitive Hashing algorithm
      in the context of image retrieval on real image databases. The results prove the
      relevance of such a new LSH scheme either providing far better accuracy in the
      context of image retrieval than euclidean scheme for an equivalent speed, or
      providing an equivalent accuracy but with a high gain in terms of processing
      speed.

PMID- 21968914
TI  - The impact of germination on the characteristics of brown rice flour and starch.
AB  - BACKGROUND: In recent years, germinated brown rice as a functional food has
      received great attention with its improved sensory and nutritional properties.
      Particularly of interest are the high levels of gamma-amino butyric acid (GABA)
      which can be obtained during germination. However, more studies are needed to
      fully understand the effect of germination on the physicochemical properties of
      brown rice. RESULT: Germination altered the chemical composition of brown rice,
      resulting in an increase in reducing sugar and ash content, and a reduction in
      amylose. Solubility, paste viscosity, transition temperatures (T(o) , T(p) and
      T(c) ) and percentage of retrogradation (%Retrogradation) were decreased, while
      swelling power and turbidity were significantly increased. Scanning electron
      micrographs indicated that starch granules from germinated brown rice became
      smaller and less homogeneous. Moreover, germination shortened the chain length of
      amylopectin and amylose molecules. CONCLUSION: This investigation provides
      information on changes in the characteristics of rice flour and rice starch
      during germination, leading to a better understanding on the chemistry of brown
      rice germination.

PMID- 21968916
TI  - Near real-time stereo matching using geodesic diffusion.
AB  - Adaptive-weight algorithms currently represent the state of the art in local
      stereo matching. However, due to their computational requirements, these types of
      solutions are not suitable for real-time implementation. Here, we present a novel
      aggregation method inspired by the anisotropic diffusion technique used in image
      filtering. The proposed aggregation algorithm produces results similar to
      adaptive-weight solutions while reducing the computational requirements.
      Moreover, near real-time performance is demonstrated with a GPU implementation of
      the algorithm.

PMID- 21968917
TI  - Exploring context and content links in social media: a latent space method.
AB  - Social media networks contain both content and context-specific information. Most
      existing methods work with either of the two for the purpose of multimedia mining
      and retrieval. In reality, both content and context information are rich sources
      of information for mining, and the full power of mining and processing algorithms
      can be realized only with the use of a combination of the two. This paper
      proposes a new algorithm which mines both context and content links in social
      media networks to discover the underlying latent semantic space. This mapping of
      the multimedia objects into latent feature vectors enables the use of any off-the
      shelf multimedia retrieval algorithms. Compared to the state-of-the-art latent
      methods in multimedia analysis, this algorithm effectively solves the problem of
      sparse context links by mining the geometric structure underlying the content
      links between multimedia objects. Specifically for multimedia annotation, we show
      that an effective algorithm can be developed to directly construct annotation
      models by simultaneously leveraging both context and content information based on
      latent structure between correlated semantic concepts. We conduct experiments on
      the Flickr data set, which contains user tags linked with images. We illustrate
      the advantages of our approach over the state-of-the-art multimedia retrieval
      techniques.

PMID- 21968918
TI  - Between vigilance and tolerance: the immune function of the intestinal
      epithelium.

PMID- 21968919
TI  - The endothelial cell protein C receptor: cell surface conductor of cytoprotective
      coagulation factor signaling.
AB  - Increasing evidence links blood coagulation proteins with the regulation of acute
      and chronic inflammatory disease. Of particular interest are vitamin K-dependent
      proteases, which are generated as a hemostatic response to vascular injury, but
      can also initiate signal transduction via interactions with vascular receptors.
      The endothelial cell protein C receptor (EPCR) is a multi-ligand vitamin K
      dependent protein receptor for zymogen and activated forms of plasma protein C
      and factor VII. Although the physiological role of the EPCR-FVII(a) interaction
      is not well-understood, protein C binding to EPCR facilitates rapid generation of
      APC in response to excessive thrombin generation, and is a central requirement
      for the multiple signal-transduction cascades initiated by APC on both vascular
      endothelial and innate immune cells. Exciting recent studies have highlighted the
      emerging role of EPCR in modulating the cytoprotective properties of APC in a
      number of diverse inflammatory disorders. In this review, we describe the
      structure-function relationships, signal transduction pathways, and cellular
      interactions that enable EPCR to modulate the anticoagulant and anti-inflammatory
      properties of its vitamin K-dependent protein ligands, and examine the relevance
      of EPCR to both thrombotic and inflammation-associated disease.

PMID- 21968920
TI  - The potter's wheel: the host's role in sculpting its microbiota.
AB  - Animals, ranging from basal metazoans to primates, are host to complex microbial
      ecosystems; engaged in a symbiotic relationship that is essential for host
      physiology and homeostasis. Epithelial surfaces vary in the composition of
      colonizing microbiota as one compares anatomic sites, developmental stages and
      species origin. Alterations of microbial composition likely contribute to
      susceptibility to several distinct diseases. The forces that shape the colonizing
      microbial composition are the focus of much current investigation, and it is
      evident that there are pressures exerted both by the host and the external
      environment to mold these ecosystems. The focus of this review is to discuss
      recent studies that demonstrate the critical importance of host factors in
      selecting for its microbiome. Greater insight into host-microbiome interactions
      will be essential for understanding homeostasis at mucosal surfaces, and
      developing useful interventions when homeostasis is disrupted.

PMID- 21968922
TI  - Biochemical reconstitution of steroid receptor*Hsp90 protein complexes and
      reactivation of ligand binding.
AB  - Hsp90 is an essential and highly abundant molecular chaperone protein that has
      been found to regulate more than 150 eukaryotic signaling proteins, including
      transcription factors (e.g. nuclear receptors, p53) and protein kinases (e.g.
      Src, Raf, Akt kinase) involved in cell cycling, tumorigenesis, apoptosis, and
      multiple eukaryotic signaling pathways (1,2). Of these many 'client' proteins for
      hsp90, the assembly of steroid receptor*hsp90 complexes is the best defined
      (Figure 1). We present here an adaptable glucocorticoid receptor (GR)
      immunoprecipitation assay and in vitro GR*hsp90 reconstitution method that may be
      readily used to probe eukaryotic hsp90 functional activity, hsp90-mediated
      steroid receptor ligand binding, and molecular chaperone cofactor requirements.
      For example, this assay can be used to test hsp90 cofactor requirements and the
      effects of adding exogenous compounds to the reconstitution process.   The GR has
      been a particularly useful system for studying hsp90 because the receptor must be
      bound to hsp90 to have an open ligand binding cleft that is accessible to steroid
      (3). Endogenous, unliganded GR is present in the cytoplasm of mammalian cells
      noncovalently bound to hsp90. As found in the endogenous  GR*hsp90 heterocomplex,
      the GR ligand binding cleft is open and capable of binding steroid. If hsp90
      dissociates from the GR or if its function is inhibited, the receptor is unable
      to bind steroid and requires reconstitution of the GR*hsp90 heterocomplex before
      steroid binding activity is restored (4) . GR can be immunoprecipitated from cell
      cytosol using a monoclonal antibody, and proteins such as hsp90 complexed to the
      GR can be assayed by western blot. Steroid binding activity of the
      immunoprecipitated GR can be determined by incubating the immunopellet with
      [(3)H]steroid.   Previous experiments have shown hsp90-mediated opening of the GR
      ligand binding cleft requires hsp70, a second molecular chaperone also essential
      for eukaryotic cell viability. Biochemical activity of hsp90 and hsp70 are
      catalyzed by co-chaperone proteins Hop, hsp40, and p23 (5).  A multiprotein
      chaperone machinery containing hsp90, hsp70, Hop, and hsp40 are endogenously
      present in eukaryotic cell cytoplasm, and reticulocyte lysate provides a
      chaperone-rich protein source (6).   In the method presented, GR is
      immunoadsorbed from cell cytosol and stripped of the endogenous hsp90/hsp70
      chaperone machinery using mild salt conditions. The salt-stripped GR is then
      incubated with reticulocyte lysate, ATP, and K(+), which results in the
      reconstitution of the GR*hsp90 heterocomplex and reactivation of steroid binding
      activity (7).  This method can be utilized to test the effects of various
      chaperone cofactors, novel proteins, and experimental hsp90 or GR inhibitors in
      order to determine their functional significance on hsp90-mediated steroid
      binding (8-11).

PMID- 21968923
TI  - Focal Reactive lesions of the Gingiva: An Analysis of 314 cases at a tertiary
      Health Institution in Nigeria.
AB  - BACKGROUND: The aim of this study was to review the clinicopathologic features of
      focal reactive gingival lesions at the Lagos University Teaching Hospital,
      Nigeria.  METHODS: A retrospective review of cases of different focal reactive
      gingival lesions from the records of the Departments of the Oral Biology/Oral
      Pathology and Oral and Maxillofacial Surgery of the Lagos University Teaching
      Hospital between 1970 and 2008 was carried out. Available clinical data regarding
      age, gender, location, estimated duration of the lesion and treatment modality
      were obtained and analyzed.  RESULTS: Prevalence rate of focal reactive gingival
      lesions was 5.6%. Pyogenic granuloma (PG) was the most common lesions
      constituting 57% of the cases. Seventeen (9.5%) of the 179 cases of PG were
      pregnancy induced pyogenic granuloma. The female-to-male ratio was 1.7:1. All the
      4 lesions occurred more in female patients than males. The mean age of patients
      at presentation was 30 +/- 16.5 years. The lesions were commonly seen in the
      second and third decade of life and least commonly seen above the age of 60
      years. The lesions were equally distributed on the maxillary and mandibular
      gingivae, and were mostly located on the buccal gingival of the jaws. Most
      (51.6%) of the lesions occurred in incisors/canine region. Recurrence of the
      lesions was seen in 9 cases (2.9%), all pyogenic granuloma.  CONCLUSION: Focal
      reactive gingival lesions are relatively uncommon lesions of the oral cavity with
      a prevalence rate of 5.6%. The lesions occurred commonly in females, and in third
      decades of life. Pyogenic granuloma was the most common lesions constituting 57%
      of all cases.

PMID- 21968924
TI  - Glycosylated analogs of formaecin I and drosocin exhibit differential pattern of
      antibacterial activity.
AB  - The synthetic glycopeptides are interesting model systems to study the effect of
      O-glycosylation in modulating their function and structure. A series of
      glycosylated analogs of two antibacterial peptides, formaecin I and drosocin,
      were synthesized by varying the nature of sugar and its linkage with bioactive
      peptides to understand the influence of structure variation of glycosylation on
      their antibacterial activities. Higher antibacterial activities of all
      glycopeptides compared to their respective non-glycosylated counterparts
      emphasize in part the importance of sugar moieties in functional implications of
      these peptides. The consequences of the unique differences among the analogs were
      apparent on their antibacterial activities but not evident structurally by
      circular dichroism studies. We have shown that differently glycosylated peptides
      exhibit differential effect among each other when tested against several Gram
      negative bacterial strains. The change of monosaccharide moiety and/or its
      anomeric configuration in formaecin I and drosocin resulted into decrease in the
      antibacterial activity in comparison to that of the native glycopeptide, but the
      extent of decrease in antibacterial activity of glycosylated drosocin analogs was
      less. Probably, the variation in peptide conformation arising due to topological
      dissimilarities among different sugars in the same peptide resulting in possible
      modulation in binding properties appears to be responsible for differences in
      their antibacterial activities. Indeed, these effects of glycosylation are found
      to be sequence-specific and depend in the milieu of amino acid residues.
      Interestingly, none of the carbohydrate variants affected the basic property of
      these peptides, which is non-hemolytic and non-toxicity to eukaryotic cells.

PMID- 21968925
TI  - Expectations from preceding prosody influence segmentation in online sentence
      processing.
AB  - Previous work examining prosodic cues in online spoken-word recognition has
      focused primarily on local cues to word identity. However, recent studies have
      suggested that utterance-level prosodic patterns can also influence the
      interpretation of subsequent sequences of lexically ambiguous syllables (Dilley,
      Mattys, & Vinke, Journal of Memory and Language, 63:274-294, 2010; Dilley &
      McAuley, Journal of Memory and Language, 59:294-311, 2008). To test the
      hypothesis that these distal prosody effects are based on expectations about the
      organization of upcoming material, we conducted a visual-world experiment. We
      examined fixations to competing alternatives such as pan and panda upon hearing
      the target word panda in utterances in which the acoustic properties of the
      preceding sentence material had been manipulated. The proportions of fixations to
      the monosyllabic competitor were higher beginning 200 ms after target word onset
      when the preceding prosody supported a prosodic constituent boundary following
      pan-, rather than following panda. These findings support the hypothesis that
      expectations based on perceived prosodic patterns in the distal context influence
      lexical segmentation and word recognition.

PMID- 21968926
TI  - Rats are sensitive to ambiguity.
AB  - In the present study, we investigated response decisions made under conditions of
      incomplete information in rats. In Experiment 1, rats were trained on either a
      positive patterning (PP; A-, B-, AB+) or a negative patterning (NP; A+, B+, AB-)
      instrumental lever-press discrimination. Subjects that had learned an NP
      discrimination responded less to Cue A when Cue B was covered at test. The cover
      did not, however, affect test responses to Cue A in the PP condition. In
      Experiment 2, rats received concurrent training on both PP and NP
      discriminations. After concurrent training, responses to Cue A were different
      with B covered versus uncovered for both NP and PP discriminations. We discuss
      possible accounts for why exposure to a nonlinearly soluble discrimination (NP)
      may have affected sensitivity to cue ambiguity produced by the cover. These
      results have interesting implications for representational processes engaged in
      problem solving.

PMID- 21968927
TI  - Adolescents with congenital heart disease: the importance of perceived parenting
      for psychosocial and health outcomes.
AB  - OBJECTIVE: : Little is known about how parenting relates to psychosocial
      functioning and health behavior in adolescents with congenital heart disease
      (CHD). Different parenting styles were identified through relying on adolescent
      perceptions of multiple dimensions (regulation, responsiveness, and psychological
      control). The degree to which parents were perceived as consistent in their
      rearing style was assessed. METHOD: : Adolescents with CHD were selected from the
      database of pediatric and congenital cardiology of the University Hospitals
      Leuven; control individuals were recruited at secondary schools. A total of 429
      adolescents (14-18 years) with CHD participated; 403 were matched on gender and
      age with control individuals. Adolescents completed questionnaires on maternal
      and paternal regulation, psychological control, and responsiveness. Main outcome
      measures were depressive symptoms, loneliness, quality of life, health status,
      alcohol, cigarette, and drug use. RESULTS: : No significant differences emerged
      between adolescents with CHD and controls in perceived parenting styles.
      Democratic parenting was accompanied by the most optimal pattern of outcomes in
      adolescents with CHD, whereas psychologically controlling parenting by the least
      optimal pattern. Overprotective parenting was related to high patient substance
      use. Perceiving both parents as democratic turned out most favorably for
      psychosocial functioning and quality of life, whereas parental consistency was
      unrelated to substance use in adolescents with CHD. DISCUSSION: : By building
      bridges between the fields of adolescent medicine and family studies, the present
      study generated important information on the role of parents in psychosocial and
      behavioral functioning of adolescents with CHD. Future longitudinal studies could
      inform family-based interventions for this population.

PMID- 21968928
TI  - ADH1B is associated with alcohol dependence and alcohol consumption in
      populations of European and African ancestry.
AB  - A coding variant in alcohol dehydrogenase 1B (ADH1B) (rs1229984) that leads to
      the replacement of Arg48 with His48 is common in Asian populations and reduces
      their risk for alcoholism, but because of very low allele frequencies the effects
      in European or African populations have been difficult to detect. We genotyped
      and analyzed this variant in three large European and African-American case
      control studies in which alcohol dependence was defined by the Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria, and
      demonstrated a strong protective effect of the His48 variant (odds ratio (OR)
      0.34, 95% confidence interval (CI) 0.24, 0.48) on alcohol dependence, with genome
      wide significance (6.6 * 10(-10)). The hypothesized mechanism of action involves
      an increased aversive reaction to alcohol; in keeping with this hypothesis, the
      same allele is strongly associated with a lower maximum number of drinks in a 24
      hour period (lifetime), with P=3 * 10(-13). We also tested the effects of this
      allele on the development of alcoholism in adolescents and young adults, and
      demonstrated a significantly protective effect. This variant has the strongest
      effect on risk for alcohol dependence compared with any other tested variant in
      European populations.

PMID- 21968921
TI  - Intracellular organelles in the saga of Ca2+ homeostasis: different molecules for
      different purposes?
AB  - An increase in the concentration of cytosolic free Ca(2+) is a key component
      regulating different cellular processes ranging from egg fertilization, active
      secretion and movement, to cell differentiation and death. The multitude of
      phenomena modulated by Ca(2+), however, do not simply rely on increases/decreases
      in its concentration, but also on specific timing, shape and sub-cellular
      localization of its signals that, combined together, provide a huge versatility
      in Ca(2+) signaling. Intracellular organelles and their Ca(2+) handling
      machineries exert key roles in this complex and precise mechanism, and this
      review will try to depict a map of Ca(2+) routes inside cells, highlighting the
      uniqueness of the different Ca(2+) toolkit components and the complexity of the
      interactions between them.

PMID- 21968929
TI  - Depression uncouples brain hate circuit.
AB  - It is increasingly recognized that we need a better understanding of how mental
      disorders such as depression alter the brain's functional connections to improve
      both early diagnosis and therapy. A new holistic approach has been used to
      investigate functional connectivity changes in the brains of patients suffering
      from major depression using resting-state functional magnetic resonance imaging
      (fMRI) data. A canonical template of connectivity in 90 different brain regions
      was constructed from healthy control subjects and this identified a six-community
      structure with each network corresponding to a different functional system. This
      template was compared with functional networks derived from fMRI scans of both
      first-episode and longer-term, drug resistant, patients suffering from severe
      depression. The greatest change in both groups of depressed patients was
      uncoupling of the so-called 'hate circuit' involving the superior frontal gyrus,
      insula and putamen. Other major changes occurred in circuits related to risk and
      action responses, reward and emotion, attention and memory processing. A voxel
      based morphometry analysis was also carried out but this revealed no evidence in
      the depressed patients for altered gray or white matter densities in the regions
      showing altered functional connectivity. This is the first evidence for the
      involvement of the 'hate circuit' in depression and suggests a potential
      reappraisal of the key neural circuitry involved. We have hypothesized that this
      may reflect reduced cognitive control over negative feelings toward both self and
      others.

PMID- 21968930
TI  - Mechanisms of initiation and reversal of drug-seeking behavior induced by
      prenatal exposure to glucocorticoids.
AB  - Stress and exposure to glucocorticoids (GC) during early life render individuals
      vulnerable to brain disorders by inducing structural and chemical alterations in
      specific neural substrates. Here we show that adult rats that had been exposed to
      in utero GCs (iuGC) display increased preference for opiates and ethanol, and are
      more responsive to the psychostimulatory actions of morphine. These animals
      presented prominent changes in the nucleus accumbens (NAcc), a key component of
      the mesolimbic reward circuitry; specifically, cell numbers and dopamine (DA)
      levels were significantly reduced, whereas DA receptor 2 (Drd2) mRNA expression
      levels were markedly upregulated in the NAcc. Interestingly, repeated morphine
      exposure significantly downregulated Drd2 expression in iuGC-exposed animals, in
      parallel with increased DNA methylation of the Drd2 gene. Administration of a
      therapeutic dose of L-dopa reverted the hypodopaminergic state in the NAcc of
      iuGC animals, normalized Drd2 expression and prevented morphine-induced
      hypermethylation of the Drd2 promoter. In addition, L-dopa treatment promoted
      dendritic and synaptic plasticity in the NAcc and, importantly, reversed drug
      seeking behavior. These results reveal a new mechanism through which drug-seeking
      behaviors may emerge and suggest that a brief and simple pharmacological
      intervention can restrain these behaviors in vulnerable individuals.

PMID- 21968931
TI  - The CHRNA5-A3-B4 gene cluster in nicotine addiction.
AB  - Nicotine addiction (NA) is a common and devastating disease, such that the annual
      number of deaths (world-wide) from tobacco-related diseases will double from 5
      million in the year 2000 to 10 million in 2020. Nicotine is the only substance in
      tobacco which animals and humans will self-administer. NA, as a lifetime
      diagnosis, has been assessed in various approaches, including the concept of
      cigarettes per day (CPD). Other assessments of NA are somewhat more
      comprehensive, such as the Fagerstrom Test for Nicotine Dependence or the
      American Psychiatric Association's Diagnostic and Statistical Manual (fourth
      edition) diagnosis of nicotine dependence. These different measures have moderate
      agreement with one another. Twin, family and adoption studies have shown that
      these different assessments of NA have substantial heritability (that fraction of
      risk attributable to genetic factors). The heritability of NA has been estimated
      at 50-75%, depending on the definition and the population under study. DNA-based
      studies of NA have been somewhat successful in identifying a common haplotype,
      which increases risk for NA among European-origin populations. This haplotype
      explains a small amount of variance, accounting for ~1 CPD, and it includes the
      alpha5 and the alpha3 nicotinic receptor subunit genes (CHRNA5 and CHRNA3). The
      review will focus on this implicated region. In this risk region, there is a
      common (among European-origin people) mis-sense single-nucleotide polymorphism in
      the CHRNA5 gene (D398N), which changes a conserved amino acid from aspartic acid
      to asparagine. The risk allele (398N) confers decreased calcium permeability and
      more extensive desensitization, according to in vitro cellular studies, raising
      the possibility that a positive allosteric modulator of the
      (alpha4beta2)(2)alpha5 type of nicotinic receptor might have therapeutic
      potential in NA. There are other genetic influences on NA in this region, apart
      from the mis-sense variant, and additional biological experiments must be done to
      understand them.

PMID- 21968932
TI  - Promoter polymorphisms in two overlapping 6p25 genes implicate mitochondrial
      proteins in cognitive deficit in schizophrenia.
AB  - In a previous study, we detected a 6p25-p24 region linked to schizophrenia in
      families with high composite cognitive deficit (CD) scores, a quantitative trait
      integrating multiple cognitive measures. Association mapping of a 10 Mb interval
      identified a 260 kb region with a cluster of single-nucleotide polymorphisms
      (SNPs) significantly associated with CD scores and memory performance. The region
      contains two colocalising genes, LYRM4 and FARS2, both encoding mitochondrial
      proteins. The two tagging SNPs with strongest evidence of association were
      located around the overlapping putative promoters, with rs2224391 predicted to
      alter a transcription factor binding site (TFBS). Sequencing the promoter region
      identified 22 SNPs, many predicted to affect TFBSs, in a tight linkage
      disequilibrium block. Luciferase reporter assays confirmed promoter activity in
      the predicted promoter region, and demonstrated marked downregulation of
      expression in the LYRM4 direction under the haplotype comprising the minor
      alleles of promoter SNPs, which however is not driven by rs2224391. Experimental
      evidence from LYRM4 expression in lymphoblasts, gel-shift assays and modelling of
      DNA breathing dynamics pointed to two adjacent promoter SNPs, rs7752203
      rs4141761, as the functional variants affecting expression. Their C-G alleles
      were associated with higher transcriptional activity and preferential binding of
      nuclear proteins, whereas the G-A combination had opposite effects and was
      associated with poor memory and high CD scores. LYRM4 is a eukaryote-specific
      component of the mitochondrial biogenesis of Fe-S clusters, essential cofactors
      in multiple processes, including oxidative phosphorylation. LYRM4 downregulation
      may be one of the mechanisms involved in inefficient oxidative phosphorylation
      and oxidative stress, increasingly recognised as contributors to schizophrenia
      pathogenesis.

PMID- 21968933
TI  - De novo induction of amyloid-beta deposition in vivo.
AB  - Alzheimer's disease (AD), the most common type of senile dementia, is associated
      to the build-up of misfolded amyloid-beta (Abeta) in the brain. Although
      compelling evidences indicate that the misfolding and oligomerization of Abeta is
      the triggering event in AD, the mechanisms responsible for the initiation of
      Abeta accumulation are unknown. In this study, we show that Abeta deposition can
      be induced by injection of AD brain extracts into animals, which, without
      exposure to this material, will never develop these alterations. The accumulation
      of Abeta deposits increased progressively with the time after inoculation, and
      the Abeta lesions were observed in brain areas far from the injection site. Our
      results suggest that some of the typical brain abnormalities associated with AD
      can be induced by a prion-like mechanism of disease transmission through
      propagation of protein misfolding. These findings may have broad implications for
      understanding the molecular mechanisms responsible for the initiation of AD, and
      may contribute to the development of new strategies for disease prevention and
      intervention.

PMID- 21968934
TI  - Uniform B-Spline Curve Interpolation with Prescribed Tangent and Curvature
      Vectors.
AB  - This paper presents a geometric algorithm for the generation of uniform cubic B
      spline curves interpolating a sequence of data points under tangent and curvature
      vectors constraints. To satisfy these constraints, knot insertion is used to
      generate additional control points which are progressively repositioned using
      corresponding geometric rules. Compared to existing schemes, our approach is
      capable of handling plane as well as space curves, has local control, and avoids
      the solution of the typical linear system. The effectiveness of the proposed
      algorithm is illustrated through several comparative examples. Applications of
      the method in NC machining and shape design are also outlined. 

PMID- 21968935
TI  - Inference-based surface reconstruction of cluttered environments.
AB  - We present an inference-based surface reconstruction algorithm that is capable of
      identifying objects of interest among a cluttered scene, and reconstructing solid
      model representations even in the presence of occluded surfaces. Our proposed
      approach incorporates a predictive modeling framework that uses a set of user
      provided models for prior knowledge, and applies this knowledge to the iterative
      identification and construction process. Our approach uses a local to global
      construction process guided by rules for fitting high-quality surface patches
      obtained from these prior models. We demonstrate the application of this
      algorithm on several example data sets containing heavy clutter and occlusion.

PMID- 21968936
TI  - [Balint group work in Germany - results from a survey of Balint group leaders].
AB  - OBJECTIVES: Based on a postal survey of Balint group leaders from the year 2004,
      this study analyses the characteristics of Balint group work as described by
      Michael Balint (1896-1970)in modern Germany. METHOD: A questionnaire was sent to
      503 German Balint group leaders, 333 (66.2 %) of whom returned the questionnaire
      (40.5 % women, mean age 57.2 years). RESULTS: Most Balint group leaders are
      specialists in psychosomatic medicine and psychotherapy (30.6 %), psychiatry and
      psychotherapy (17.1 %) or are general practitioners (12.3 %). Psychoanalysts
      rarely serve as Balint group leaders. Sessions are normally held every 2 weeks
      (26.7 %) or once a month (26.4 %). Despite the original intention of Michael
      Balint, the idea of holding weekly Balint groups is now seldom(3.9 %). 85 %of the
      Balint group leaders prefer sessions lasting 90 minutes. An average of 8.6
      participants attend, with 2.1 persons missing. There is a great heterogeneity in
      the professions of Balint group leaders. 17.4 % of them are older 65 years.
      CONCLUSIONS: This study shows that Balint group work in Germany is well
      integrated in both general practice and psychotherapy, and it is still of great
      interest to many specialists of other disciplines as well as a good way to
      realize further education. The ideas of Michael Balint are very much alive, but -
      because of the changed realities in the medical field - no longer as he
      originally foresaw, but in settings adapted to the new situations in medicine.

PMID- 21968937
TI  - [Prevalence and comorbidity of somatoform disorder in psychosomatic inpatients: a
      multicentre study].
AB  - OBJECTIVES: This epidemiological multicenter study investigates the prevalence
      and comorbidity of somatoform disorder in psychosomatic inpatients. METHODS:
      Twenty psychosomatic hospitals collected the diagnoses of all treated patients in
      the years 1998 to 2007. The data were analysed at the "Institute for Quality
      Assurance in Psychotherapy and Psychosomatic Medicine" (IQP),Munich. RESULTS: Of
      the 100,607 patients surveyed, 18,492 (18.4 %) fulfilled the ICD-10 criteria for
      a somatoform disorder. 91.9 % of patients with somatoform disorder have at least
      one, on average 2.8 additional psychiatric disorders. The mean duration of the
      symptoms before current treatment was 62.6 months. CONCLUSIONS: The prevalence of
      somatoform disorder in psychosomatic inpatients is comparable to that found in
      data from internal or general medicine patients. However, there are major
      differences in the distribution of the diagnostic subgroups of somatoform
      disorder.

PMID- 21968938
TI  - [Alexithymia and specific relationship patterns in a clinical sample].
AB  - OBJECTIVES: Alexithymia is characterized by deficits in perceiving,
      differentiating and regulating affects, both one's own affects and those of
      others. It is often related to interpersonal problems which are a major reason
      for seeking psychotherapy. This study assesses the relationship between
      alexithymia, specific relationship patterns and interpersonal problems in a
      clinical inpatient sample. METHODS: We evaluated alexithymia (Toronto-Alexithymia
      Scale-26: TAS-26), relationship patterns (Relationship Patterns Questionnaire-II;
      RPQ-II) and interpersonal problems (Inventory of Interpersonal Problems: IIP) in
      152 patients with various mental disorders upon admission to an inpatient clinic
      for psychosomatic medicine and psychotherapy. RESULTS: Alexithymia (TAS-20) was
      significantly negatively associated with self-assertion (RPQII) and significantly
      positively associated with overall interpersonal problems (IIP-total score).
      Specifically, the interpersonal style associated with alexithymia was
      characterized by cold, socially avoidant, nonassertive and exploitable behavior
      (IIP-subscales). CONCLUSIONS: Alexithymia in patients with mental disorders is
      linked to specific relationship patterns and interpersonal problems at the
      beginning of an inpatient psychotherapy. Because interpersonal problems, and
      especially the therapeutic alliance, are strong predictors of outcome in
      individual psychotherapy, specific attention should be paid to this relationship
      in the treatment of alexithymic patients.

PMID- 21968939
TI  - Lenalidomide enhances the anti-prostate cancer activity of docetaxel in vitro and
      in vivo.
AB  - BACKGROUND: In this study, we investigated the effects of combining lenalidomide
      and docetaxel on in vitro and in vivo models of prostate cancer as a potential
      strategy for treatment of castrate resistant prostate cancer (CRPC). METHODS: The
      effects of combining lenalidomide and docetaxel on proliferation, apoptosis,
      invasive potential, anchorage independent growth, and p53 activation in the PC3
      and DU145 prostate cell lines were investigated. The effects of the lenalidomide
      and docetaxel combination on LNCaP prostate cancer cell growth and invasiveness
      in vitro was also studied. The combination of these two agents was finally tested
      on a xenograft model of PC3 tumor growth in nude mice. RESULTS: Lenalidomide
      decreased the IC(50) of docetaxel by up to 50% (P < 0.05) and also decreased
      invasion in PC3, LNCaP, and DU145 cells and anchorage independent growth in PC3
      cells (P < 0.01). Apoptosis in lenalidomide/docetaxel-treated cells was increased
      by 2.2-fold over single agent docetaxel and a corresponding increase in p53, p38,
      and BAD activation was observed in Western blots (P < 0.001). When PC3 challenged
      mice were treated with lenalidomide and docetaxel, median survival increased from
      48 to 59 days and the rate of tumor growth was significantly reduced (P < 0.05).
      CONCLUSIONS: Lenalidomide may be a promising candidate for combination with
      docetaxel in the treatment of CRPC.

PMID- 21968940
TI  - Factors influencing respirator use at work in respiratory patients.
AB  - BACKGROUND: When engineering controls such as ventilation are not sufficient to
      prevent hazardous exposures in workplaces, respiratory protective devices (RPDs)
      may be provided to decrease workers' exposures. Often, workers do not use RPDs
      consistently when required. AIMS: Our goal was to determine important factors
      associated with RPD usage in workers with respiratory disease exposed to airborne
      hazards at work. METHODS: One hundred and twenty-nine respiratory clinic patients
      in jobs with self-identified hazardous airborne substances completed a
      questionnaire and their clinic files were reviewed. Statistical analysis using
      chi-squared test and binary logistical regression was done to identify
      associations with RPD usage. RESULTS: Forty-one per cent reported always wearing
      RPDs whenever a hazard was present; 33% never wore RPD. Compliance was highest
      among healthcare workers (72%) and lowest among workers in food and service
      industries (13 and 22%, respectively), P < 0.01. The compliance of co-workers,
      conveniently located RPDs, safety training discussing the use of RPDs, fit
      testing available at the workplace and age were positively associated with
      compliance (P < 0.05). Experiencing symptoms of shortness of breath and nasal
      stuffiness were negatively associated with compliance (P < 0.05). CONCLUSIONS:
      Addressing company factors and workers' symptoms apparently influencing
      compliance may optimize RPD usage.

PMID- 21968941
TI  - Molecular operation of metals into the function and state of photosystem II.
AB  - Action sites of different metals in the electron transport reactions of
      Photosystem II (PS II) evaluated by delayed fluorescence in the ms range (ms DF)
      and pigment-pigment, pigment-protein and protein-protein interaction states by
      electrophoretic measurements are presented. The main targets for the metals
      action were shown to be:(i) Cd(2+), Ni(2+), Co(2+)-Y(z) or CaMn(4)-cluster on the
      donor site with dependence on pH;(ii) Ni(2+), Co(2+), Zn(2+), Al(3+), Mn(2+)
      between Q(A) and Q(B) on the acceptor site; effect of Al(3+) and Mn(2+) is
      observed only in acidic pH. Investigated metals bring about monomerization of
      oligomeric and dimeric chlorophyll-protein complexes (CPC) and destabilization of
      protein-protein interactions. Molecular mechanisms of metals interference with
      the structure of PS II are discussed.

PMID- 21968942
TI  - Association of serum uric acid with Pro12Ala polymorphism in PPAR-gamma2 among
      Chinese nonagenarians/centenarians.
AB  - BACKGROUND AND AIMS: In previous studies, Pro12Ala polymorphism in peroxisome
      proliferator- activated receptors gamma 2 (PPAR-gamma2) was shown to be
      associated with both longevity and metabolic syndrome, which was closely related
      with hyperuricemia. We examined long-lived subjects (>=90 years), to ascertain
      whether the polymorphism is associated with the level of serum uric acid (SUA).
      METHODS: The present study analysed data from a survey conducted in 2005 on all
      residents aged 90 years or more in a district with 2,311,709 inhabitants.
      RESULTS: The sample comprised 669 unrelated Chinese participants (aged 90-108
      years, mean: 93.54+/-3.53 years; 67.2% women). The genotype frequencies of the
      Pro12Ala polymorphism were 0% Ala12Ala and 9.0% Pro12Ala, 91.0% Pro12Pro. Between
      men or women, and between subjects who were or were not 12Ala carriers, neither
      in SUA levels nor the prevalence of hyperuricemia were significant. Between
      subjects with and without hyperuricemia, the difference in prevalence of 12Ala
      carriers was also non-significant. Unadjusted and adjusted multiple logistic
      regressions showed that the odds ratios (OR) for hyperuricemia were not
      associated with Pro12Ala polymorphism in PPAR-gamma2. CONCLUSIONS: In Chinese
      nonagenarians and centenarians, SUA levels are not associated with polymorphism
      in PPAR-gamma2.

PMID- 21968943
TI  - A phase II study of O6-benzylguanine and temozolomide in pediatric patients with
      recurrent or progressive high-grade gliomas and brainstem gliomas: a Pediatric
      Brain Tumor Consortium study.
AB  - To estimate the sustained (>=8 weeks) objective response rate in pediatric
      patients with recurrent or progressive high-grade gliomas (HGG, Stratum A) or
      brainstem gliomas (BSG, Stratum B) treated with the combination of O6
      benzylguanine (O6BG) and temozolomide((r)) (TMZ). Patients received O6BG 120
      mg/m(2)/d IV followed by TMZ 75 mg/m(2)/d orally daily for 5 consecutive days of
      each 28-day course. The target objective response rate to consider the
      combination active was 17%. A two-stage design was employed. Forty-three patients
      were enrolled; 41 were evaluable for response, including 25 patients with HGG and
      16 patients with BSG. The combination of O6BG and TMZ was tolerable, and the
      primary toxicities were myelosuppression and gastrointestinal symptoms. One
      sustained (>=8 weeks) partial response was observed in the HGG cohort; no
      sustained objective responses were observed in the BSG cohort. Long-term (>=6
      courses) stable disease (SD) was observed in 4 patients in Stratum A and 1
      patient in Stratum B. Of the 5 patients with objective response or long-term SD,
      3 underwent central review with 2 reclassified as low-grade gliomas. The
      combination of O6BG and TMZ did not achieve the target response rate for activity
      in pediatric patients with recurrent or progressive HGG and BSG.

PMID- 21968944
TI  - O6-methylguanine-DNA methyltransferase promoter methylation in 45 primary central
      nervous system lymphomas: quantitative assessment of methylation and response to
      temozolomide treatment.
AB  - Favorable responses to temozolomide chemotherapy have recently been reported in
      primary central nervous system lymphoma (PCNSL) patients who are refractory to
      high-dose methotrexate therapy. The gene encoding the DNA repair enzyme O (6)
      methylguanine-DNA methyltransferase (MGMT) is transcriptionally silenced by
      promoter methylation in several human tumors, including gliomas and systemic
      lymphomas. MGMT promoter methylation is also a prognostic marker in glioblastoma
      patients treated with temozolomide. To validate temozolomide treatment in PCNSL,
      we applied methylation-sensitive high resolution melting (MS-HRM) analysis to
      quantitate MGMT methylation in PCNSL. MGMT promoter methylation was detected in
      tumors from 23 (51%) of 45 PCNSL patients, 11 of which were considered to have
      high (more than 70.0%) methylation status. Of the five recurrent PCNSLs treated
      with temozolomide, four cases responded, with three achieving complete response
      and one, a partial response. All four responsive PCNSLs had methylated MGMT
      promoters, whereas the non-responsive recurrent PCNSL did not. Thus, the use of
      quantitative MS-HRM analysis for the detection of MGMT promoter methylation has
      been suggested in PCNSL for the first time. The assay allows rapid and high
      throughput evaluation of the MGMT methylation status, and seems to be promising
      in clinical settings. MGMT promoter methylation may become a useful marker for
      predicting the response of PCNSLs to temozolomide.

PMID- 21968945
TI  - Brain biopsy is required in steroid-resistant patients with chronic lymphocytic
      inflammation with pontine perivascular enhancement responsive to steroids
      (CLIPPERS).

PMID- 21968946
TI  - The burden of brain tumor: a single-institution study on psychological patterns
      in caregivers.
AB  - Quality of life and well-being in caregivers are usually partly neglected since
      all attention is focused on patients and the way they react to the illness.
      Carers also usually neglect their own needs, especially when the illness of the
      patient is as complex as a brain tumor. The aim of this study is to investigate
      how caregivers deal with a diagnosis of brain tumor in their relatives and how
      they manage their quality of life and psychosocial well-being. One hundred
      primary caregivers of patients with brain tumors were interviewed and were asked
      to fill in self-administered questionnaires detecting multidimensional levels of
      quality of life, anxiety, depression, and psychosocial reaction to the patient's
      illness. Data were related with some functional and psychosocial information
      collected about the patient's disease. Caregivers try to react to the illness of
      their relatives by mobilizing their physical reaction and growing their self
      esteem, but they live with a clinically significant impairment of their quality
      of life, and experience a deep level of anxiety and depression. The caregivers'
      burden appears mainly in their ability to provide care and in financial strain.
      The length of disease and the functional status of patients significantly
      influence caregivers' psychosocial well-being. Despite the appearance they want
      to show their affected relatives, caregivers suffer from deep limitation in their
      quality of life. The relevance of caregivers' burden suggests the importance of
      psychological support to improve reaction to the illness.

PMID- 21968948
TI  - Individual and joint toxicity effects of Cu, Cr(III), and Cr(VI) on pakchoi: a
      comparison between solution and soil cultures.
AB  - The single and joint toxicity effects of Cu, Cr(III), and Cr(VI) on the root
      elongation of pakchoi in solution and soil were investigated. The median
      effective concentration (EC(50)) was determined to examine the toxic thresholds
      of the test elements. The results showed that individual contamination by Cu,
      Cr(III), or Cr(VI) can inhibit the root elongation of pakchoi. The EC(50) values
      of the test elements were 2.02 mg/L and 195.8 mg/kg, 62.2 mg/L and 1,773 mg/kg,
      and 6.88 mg/L and 8.08 mg/kg in solution and soil, respectively. Toxic unit (TU)
      was introduced to determine the outcome in combined tests, and different
      behaviors were observed in both solution and soil. The coexistence of Cu and
      Cr(III) in solution exhibited an antagonistic effect (EC(50mix) = 1.76 TU(mix)),
      whereas a synergistic effect was observed in soil (EC(50mix) = 0.76 TU(mix)). In
      contrast, combined Cu-Cr(VI) showed a less than additive toxicity both in
      solution and soil, with EC(50mix) values of 3.31 and 1.24 TU(mix). In conclusion,
      the coexistence of toxicity in Cu-Cr(III) and Cu-Cr(VI) differs from the toxicity
      exhibited individually by Cu, Cr(III), and Cr(VI). Heavy metal interaction also
      changes depending on the medium.

PMID- 21968947
TI  - Autoantibodies to estrogen receptor alpha interfere with T lymphocyte homeostasis
      and are associated with disease activity in systemic lupus erythematosus.
AB  - OBJECTIVE: Estrogens influence many physiologic processes and are also implicated
      in the development or progression of numerous diseases, including autoimmune
      disorders. Aberrations of lymphocyte homeostasis that lead to the production of
      multiple pathogenic autoantibodies, including autoantibodies specific to estrogen
      receptor (ER), have been detected in the peripheral blood of patients with
      systemic lupus erythematosus (SLE). This study was undertaken to assess the
      presence of both anti-ERalpha and anti-ERbeta antibodies in sera from patients
      with SLE, to analyze the effect of these antibodies on peripheral blood T
      lymphocyte homeostasis, and to evaluate their role as determinants of disease
      pathogenesis and progression. METHODS: Anti-ER antibody serum immunoreactivity
      was analyzed by enzyme-linked immunosorbent assay in samples from 86 patients
      with SLE and 95 healthy donors. Phenotypic and functional analyses were performed
      by flow cytometry and Western blotting. RESULTS: Anti-ERalpha antibodies were
      present in 45% of the patients with SLE, whereas anti-ERbeta antibodies were
      undetectable. In healthy donors, anti-ERalpha antibodies induced cell activation
      and consequent apoptotic cell death in resting lymphocytes as well as
      proliferation of anti-CD3-stimulated T lymphocytes. A significant association
      between anti-ERalpha antibody values and clinical parameters, i.e., the SLE
      Disease Activity Index and arthritis, was found. CONCLUSION: Our data suggest
      that anti-ERalpha autoantibodies interfere with T lymphocyte homeostasis and are
      significantly associated with lupus disease activity.

PMID- 21968949
TI  - Effects of cobalt nanoparticles on human T cells in vitro.
AB  - Limited information is available on the potential risk of degradation products of
      metal-on-metal bearings in joint arthroplasty. The aim of this study was to
      investigate the cytotoxicity and genotoxicity of orthopedic-related cobalt
      nanoparticles on human T cells in vitro. T cells were collected using magnetic
      CD3 microbeads and exposed to different concentrations of cobalt nanoparticles
      and cobalt chloride. Cytotoxicity was evaluated by methyl thiazolyl tetrazolium
      and lactate dehydrogenase release assay. Cobalt nanoparticles dissolution in
      culture medium was determined by inductively coupled plasma-mass spectrometry. To
      study the probable mechanism of cobalt nanoparticles effects on T cells,
      superoxide dismutase, catalase, and glutathione peroxidase level was measured.
      Cobalt nanoparticles and cobalt ions could inhibit cell viability and enhance
      lactate dehydrogenase release in a concentration- and time-dependent manner (P <
      0.05). The levels of cobalt ion released from cobalt nanoparticles in the culture
      medium were less than 40% and increased with cobalt nanoparticles concentration.
      Cobalt nanoparticles could induce primary DNA damage in a concentration-dependent
      manner, and the DNA damage caused by cobalt nanoparticles was heavier than that
      caused by cobalt ions. Cobalt nanoparticles exposure could significantly decrease
      superoxide dismutase, catalase, and glutathione peroxidase activities at subtoxic
      concentrations (6 MUM, <CC(50)). These findings suggested that cobalt
      nanoparticles could generate potential risks to the T cells of patients suffer
      from metal-on-metal total hip arthroplasty, and the inhibition of antioxidant
      capacity may play important role in cobalt nanoparticles effects on T cells.

PMID- 21968950
TI  - Debio 0507 primarily forms diaminocyclohexane-Pt-d(GpG) and -d(ApG) DNA adducts
      in HCT116 cells.
AB  - PURPOSE: To characterize the cellular action mechanism of Debio 0507, we compared
      the major DNA adducts formed by Debio 0507- and oxaliplatin-treated HCT116 human
      colon carcinoma cells by a combination of inductively coupled plasma mass
      spectrometry (ICP-MS) and ultraperformance liquid chromatography mass
      spectrometry (UPLC-MS/MS). METHODS: HCT116 cells were treated with IC(50) doses
      of Debio 0507 or oxaliplatin for 3 days. Total cellular Pt-DNA adducts were
      determined by ICP-MS. The DNA was digested, and the major Pt-DNA adducts formed
      by both drugs were characterized by UPLC/MS/MS essentially as described
      previously for cisplatin (Baskerville-Abraham et al. in Chem Res Toxicol 22:905
      912, 2009). RESULTS: The Pt level/deoxynucleotide was 7.4/10(4) for DNA from
      Debio 0507-treated cells and 5.5/10(4) for oxaliplatin-treated cells following a
      3-day treatment at the IC(50) for each drug. UPLC-MS/MS in the positive ion mode
      confirmed the major Pt-DNA adducts formed by both drugs were dach-Pt-d(GpG)
      (904.2 m/z -> 610 m/z and 904.2 m/z -> 459 m/z) and dach-Pt-d(ApG) (888.2 m/z ->
      594 m/z and 888.2 m/z -> 459 m/z). CONCLUSIONS: These data show that the major
      DNA adducts formed by Debio 0507 are the dach-Pt-d(GpG) and dach-Pt-d(ApG)
      adducts and at equitoxic doses Debio 0507 and oxaliplatin form similar levels of
      dach-Pt-d(GpG) and dach-Pt-d(ApG) adducts. This suggests that the action
      mechanisms of Debio 0507 and oxaliplatin are similar at a cellular level.

PMID- 21968951
TI  - Impact of plasma and intracellular exposure and CYP3A4, CYP3A5, and ABCB1 genetic
      polymorphisms on vincristine-induced neurotoxicity.
AB  - PURPOSE: The aim of this study was to investigate the impact of plasma and
      intracellular exposure and CYP3A4, CYP3A5, and ABCB1 polymorphisms on vincristine
      neurotoxicity. We subsequently assessed the impact of ABCB1 polymorphisms on
      intracellular vincristine accumulation. METHODS: Children treated for solid
      tumors were enrolled in the study (n = 26) and received 1.5 mg/m2 of vincristine
      per course. Individual pharmacokinetic parameters and CYP3A4, CYP3A5, and ABCB1
      genotypes were available from a previous analysis. A global toxicity score (pain,
      peripheral neurotoxicity, and gastrointestinal toxicity) was collected at each
      course. Vincristine in plasma and PBMCs were quantified by LC-MS/MS. RESULTS:
      Vincristine plasma and intracellular concentrations ranged from 0.40 to 89.6
      ng/ml and from 0.00225 to 1.85 ng/10(6) cells over a 24-h interval, respectively.
      The global toxicity score ranged from 0 to 6 and was not correlated with
      individual pharmacokinetics parameters. Neurotoxicity events (global score >= 3)
      were observed in 8 patients but the incidence was not influenced by the different
      studied polymorphisms. The global toxicity score was correlated with age, body
      surface area, and dose in mg. A trend to higher intracellular/plasma ratio of
      vincristine was found for patients with heterozygous diplotype (CGC-TTT) of
      ABCB1. CONCLUSIONS: None of the different genetic covariates nor plasma and
      intracellular exposure was predictive of the observed neurotoxicity in our
      pediatric population. Nevertheless, the heterozygote diplotype of ABCB1 appears
      to influence the intracellular accumulation of vincristine. Owing to the small
      sample size, further evaluations are needed in a larger patient cohort.

PMID- 21968952
TI  - Enhancement of curcumin oral absorption and pharmacokinetics of curcuminoids and
      curcumin metabolites in mice.
AB  - PURPOSE: Curcumin has shown a variety of biological activity for various human
      diseases including cancer in preclinical setting. Its poor oral bioavailability
      poses significant pharmacological barriers to its clinical application. Here, we
      established a practical nano-emulsion curcumin (NEC) containing up to 20%
      curcumin (w/w) and conducted the pharmacokinetics of curcuminoids and curcumin
      metabolites in mice. METHODS: This high loading NEC was formulated based on the
      high solubility of curcumin in polyethylene glycols (PEGs) and the synergistic
      enhancement of curcumin absorption by PEGs and Cremophor EL. The pharmacokinetics
      of curcuminoids and curcumin metabolites was characterized in mice using a LC
      MS/MS method, and the pharmacokinetic parameters were determined using WinNonlin
      computer software. RESULTS: A tenfold increase in the AUC (0->24h) and more than
      40-fold increase in the C (max) in mice were observed after an oral dose of NEC
      compared with suspension curcumin in 1% methylcellulose. The plasma
      pharmacokinetics of its two natural congeners, demethoxycurcumin and
      bisdemethoxycurcumin, and three metabolites, tetrahydrocurcumin (THC), curcumin-O
      glucuronide, and curcumin-O-sulfate, was characterized for the first time in mice
      after an oral dose of NEC. CONCLUSION: This oral absorption enhanced NEC may
      provide a practical formulation to conduct the correlative study of the PK of
      curcuminoids and their pharmacodynamics, e.g., hypomethylation activity in vivo.

PMID- 21968953
TI  - Phase II study of use of a single cycle of induction chemotherapy and concurrent
      chemoradiotherapy containing capecitabine/cisplatin followed by surgery for
      patients with resectable esophageal squamous cell carcinoma: long-term follow-up
      data.
AB  - PURPOSE: This phase II study evaluated the feasibility and efficacy of one cycle
      of induction chemotherapy, followed by concurrent chemoradiotherapy (CRT)
      featuring capecitabine/cisplatin, followed in turn by surgery, in the treatment
      of patients with resectable esophageal squamous cell carcinoma. METHODS: Between
      March 2003 and April 2005, 54 patients with stage II or III esophageal cancer
      were treated with induction chemotherapy (cisplatin 60 mg/m(2) on day 1;
      capecitabine 1,000 mg/m(2) bid on days 1-14) followed by concurrent radiotherapy
      (46 Gy in 23 fractions) and chemotherapy (cisplatin 30 mg/m(2) on days 1, 8, 15,
      and 22; capecitabine 800 mg/m(2) bid 5 days/week). Surgery was performed within 8
      weeks of the end of radiotherapy. RESULTS: Median age of the patients was 64.5
      years (range, 45-74 years). After CRT, 52 patients (96%) showed a clinical
      response, including 26 (48%) who exhibited a complete response (CR). Surgery was
      performed on 41 patients (76%), with 20 (37%) achieving pathologic CR and 3 (6%)
      dying of postoperative pneumonia. At a median follow-up time of 74.2 months
      (range, 64.3-84.8 months), 16 patients (30%) had experienced tumor recurrence and
      36 (67%) had died. Of the 41 patients who underwent esophagectomy, 5 (12%) had
      exclusively locoregional disease and 7 (17%) had distant metastasis, whereas no
      one had both. The 5-year progression-free and overall survival rates were 30.2%
      (95% confidence interval [CI], 18.0-42.4%) and 37.0% (95% CI, 24.1-50.0%),
      respectively. CONCLUSIONS: A trimodal approach, consisting of a single cycle of
      induction chemotherapy, CRT containing capecitabine and cisplatin, and surgery,
      was feasible and effective in patients with resectable esophageal squamous cell
      carcinoma.

PMID- 21968954
TI  - Necrotic enteritis due to simultaneous infection with Isospora suis and
      clostridia in newborn piglets and its prevention by early treatment with
      toltrazuril.
AB  - In this study, 51 piglets originating from five different sows were included in
      the investigations. The animal source of all sows had a history of Clostridium
      perfringens type A (beta2) infection. The piglets of three sows (n = 31) were
      experimentally infected with Isospora suis within the first 4 h after birth and
      were randomly assigned to the treatment group or the sham-dosing group. The
      piglets of the two remaining sows (n = 20) served as I. suis-uninfected controls.
      Twelve hours post-infection, the animals in the treatment group (n = 15) were
      treated with toltrazuril (20 mg/kg BW, Baycox(r) 5% suspension). During an
      observation period of 14 days faecal consistency, faecal oocyst counts, faecal
      germ counts, mortality, body weight development and clinical status were
      recorded. One piglet per study group and litter was necropsied, and intestinal
      tissue samples were taken for histopathological investigations and in situ
      hybridisation on study days (SDs) 3 and 14. I. suis-infected but untreated
      piglets showed clinical disease resulting in liquefaction of faeces and decreased
      body weight development. In 59.2% of the observations, I. suis-infected but
      untreated piglets showed abnormal faecal consistencies whereas only 12.0% or
      respectively 4.4% of the faecal samples had a pasty consistency in the I. suis
      infected-treated or in the control animals. The mean body weight at the end of
      the study was 3.37 kg in the I. suis-infected but untreated piglets while the
      average body weight in the I. suis-infected-treated animals was calculated as
      4.42 kg and the control animal's mean body weight was 4.45 kg. Moreover,
      mortality, occurring between SDs 8 and 14, in this study group was 38.5% (n = 5),
      with 30.8% (n = 4) died from necrotic enteritis. In contrast, no piglets died in
      the I. suis-uninfected control group or in the toltrazuril-treated study group.
      The results of this study corroborate the hypothesis that simultaneous infection
      with I. suis and C. perfringens type A soon after birth leads to distinct
      interactions between the two pathogens and result in an increase in clinical
      disease, mortality and metabolically active C. perfringens type A.

PMID- 21968955
TI  - Inflammatory cytokines IFN-gamma, IL-4, IL-13 and TNF-alpha alterations in
      schistosomiasis: a meta-analysis.
AB  - Cytokines play an important role in the immunological pathogenesis of
      schistosomiasis. Schistosomiasis would be associated with an imbalance in
      inflammatory cytokines that leads to a decrease of T helper (Th) 1 and an
      increase of Th2 cytokine secretion. Corresponding data so far have been
      inconsistent, so we performed a meta-analysis to assess whether cytokine
      alterations were risk factors for schistosomiasis progression. We searched
      MEDLINE, EMBASE, and CNKI databases for literatures including abstracts, reviews,
      and reference lists. Our studies included assessment of cytokine concentrations
      in vivo plasma or serum and secretion of cytokines in vitro by peripheral blood
      leukocytes from schistosomiasis patients or infected individuals with
      schistosome. The prototypic Th1 and Th2 cytokines IFN-gamma and interleukin (IL)
      4 were assessed as well as IL-13 and tumor necrosis factor-alpha (TNF-alpha). The
      results implied that an increase occurs in TNF-alpha and IL-4 with
      schistosomiasis progression.

PMID- 21968956
TI  - Algorithms to detect multiprotein modularity conserved during evolution.
AB  - Detecting essential multiprotein modules that change infrequently during
      evolution is a challenging algorithmic task that is important for understanding
      the structure, function, and evolution of the biological cell. In this paper, we
      define a measure of modularity for interactomes and present a linear-time
      algorithm, Produles, for detecting multiprotein modularity conserved during
      evolution that improves on the running time of previous algorithms for related
      problems and offers desirable theoretical guarantees. We present a biologically
      motivated graph theoretic set of evaluation measures complementary to previous
      evaluation measures, demonstrate that Produles exhibits good performance by all
      measures, and describe certain recurrent anomalies in the performance of previous
      algorithms that are not detected by previous measures. Consideration of the newly
      defined measures and algorithm performance on these measures leads to useful
      insights on the nature of interactomics data and the goals of previous and
      current algorithms. Through randomization experiments, we demonstrate that
      conserved modularity is a defining characteristic of interactomes. Computational
      experiments on current experimentally derived interactomes for Homo sapiens and
      Drosophila melanogaster, combining results across algorithms, show that nearly 10
      percent of current interactome proteins participate in multiprotein modules with
      good evidence in the protein interaction data of being conserved between human
      and Drosophila.

PMID- 21968957
TI  - Subcellular localization prediction through boosting association rules.
AB  - Computational methods for predicting protein subcellular localization have used
      various types of features, including N-terminal sorting signals, amino acid
      compositions, and text annotations from protein databases. Our approach does not
      use biological knowledge such as the sorting signals or homologues, but use just
      protein sequence information. The method divides a protein sequence into short
      $k$-mer sequence fragments which can be mapped to word features in document
      classification. A large number of class association rules are mined from the
      protein sequence examples that range from the N-terminus to the C-terminus. Then,
      a boosting algorithm is applied to those rules to build up a final classifier.
      Experimental results using benchmark datasets show our method is excellent in
      terms of both the classification performance and the test coverage. The result
      also implies that the $k$-mer sequence features which determine subcellular
      locations do not necessarily exist in specific positions of a protein sequence.
      Online prediction service implementing our method is available at
      http://isoft.postech.ac.kr/research/BCAR/subcell. 

PMID- 21968958
TI  - Comment on "SCS: signal, context, and structure features for genome-wide human
      promoter recognition".
AB  - We comment on the flexibility profiles calculated by Zeng et al., and show that
      these profiles do not represent the local flexibility of the DNA molecule. If one
      takes into account the physics of elasticity, the averaged flexibility profile
      show an additional peak which is missed in the original calculation. We show that
      it is not possible to calculate the flexibility of a 6-mer using tetranucleotide
      elastic constants, the shortest sequence is a 7-mer. For 6-mers, dinucleotide or
      trinucleotide parameters are needed. We present calculations for dinucleotide
      flexibility parameters and show that the same additional peak is present for both
      7-mers and 6-mers. 

PMID- 21968959
TI  - Efficient maximal repeat finding using the burrows-wheeler transform and wavelet
      tree.
AB  - Finding repetitive structures in genomes and proteins is important to understand
      their biological functions. Many data compressors for modern genomic sequences
      rely heavily on finding repeats in the sequences. The notion of maximal repeats
      captures all the repeats in the data in a space-efficient way. Prior work on
      maximal repeat finding used either a suffix tree or a suffix array along with
      other auxiliary data structures. Their space usage is 19--50 times the text size
      with the best engineering efforts, prohibiting their usability on massive data.
      Our technique uses the Burrows-Wheeler Transform and wavelet trees. For data sets
      consisting of natural language texts, the space usage of our method is no more
      than three times the text size. For genomic sequences stored using one byte per
      base, the space usage is less than double the sequence size. Our method is also
      orders of magnitude faster than the prior methods for processing massive texts,
      since the prior methods must use external memory. For the first time, our method
      enables a desktop computer with 8GB internal memory to find all the maximal
      repeats in the whole human genome in less than 17 hours. We have implemented our
      method as general-purpose open-source software for public use. 

PMID- 21968960
TI  - DICLENS: divisive clustering ensemble with automatic cluster number.
AB  - Clustering has a long and rich history in a variety of scientific fields. Finding
      natural groupings of a data set is a hard task as attested by hundreds of
      clustering algorithms in the literature. Each clustering technique makes some
      assumptions about the underlying data set. If the assumptions hold, good
      clusterings can be expected. It is hard, in some cases impossible, to satisfy all
      the assumptions. Therefore, it is beneficial to apply different clustering
      methods on the same data set, or the same method with varying input parameters or
      both. We propose a novel method, DICLENS, which combines a set of clusterings
      into a final clustering having better overall quality. Our method produces the
      final clustering automatically and does not take any input parameters, a feature
      missing in many existing algorithms. Extensive experimental studies on real,
      artificial, and gene expression data sets demonstrate that DICLENS produces very
      good quality clusterings in a short amount of time. DICLENS implementation runs
      on standard personal computers by being scalable, and by consuming very little
      memory and CPU. 

PMID- 21968961
TI  - On the elusiveness of clusters.
AB  - Rooted phylogenetic networks are often used to represent conflicting phylogenetic
      signals. Given a set of clusters, a network is said to represent these clusters
      in the softwired sense if, for each cluster, at least one tree embedded in the
      network contains it. Motivated by parsimony we might wish to construct such a
      network using as few reticulations as possible, or minimizing the level of the
      network, i.e. the maximum number of reticulations used in any "tangled" region of
      the network. Although these are NP-hard problems, here we prove that, for every
      fixed k &#x2265; 0, it is polynomial-time solvable to construct a phylogenetic
      network with level equal to k representing a cluster set, or to determine that no
      such network exists. However, this algorithm does not lend itself to a practical
      implementation. We also prove that the comparatively efficient CASS algorithm
      correctly solves this problem (and also minimizes the reticulation number) when
      input clusters are obtained from two not necessarily binary gene trees on the
      same set of taxa but does not always minimize level for general cluster sets.
      Finally, we describe a new algorithm which generates in polynomial-time all
      binary phylogenetic networks with exactly r reticulations representing a set of
      input clusters (for every fixed r &#x2265; 0). 

PMID- 21968962
TI  - Inference of biological S-system using the separable estimation method and the
      genetic algorithm.
AB  - Reconstruction of a biological system from its experimental time series data is a
      challenging task in systems biology. The S-system which consists of a group of
      nonlinear ordinary differential equations (ODEs) is an effective model to
      characterize molecular biological systems and analyze the system dynamics.
      However, inference of S-systems without the knowledge of system structure is not
      a trivial task due to its nonlinearity and complexity. In this paper, a pruning
      separable parameter estimation algorithm (PSPEA) is proposed for inferring S
      systems. This novel algorithm combines the separable parameter estimation method
      (SPEM) and a pruning strategy, which includes adding an l1 regularization term to
      the objective function and pruning the solution with a threshold value. Then,
      this algorithm is combined with the continuous genetic algorithm (CGA) to form a
      hybrid algorithm that owns the properties of these two combined algorithms. The
      performance of the pruning strategy in the proposed algorithm is evaluated from
      two aspects: the parameter estimation error and structure identification
      accuracy. The results show that the proposed algorithm with the pruning strategy
      has much lower estimation error and much higher identification accuracy than the
      existing method.

PMID- 21968963
TI  - Chemical equilibria in the binary and ternary uranyl(VI)-hydroxide-peroxide
      systems.
AB  - The composition and equilibrium constants of the complexes formed in the binary
      U(VI)-hydroxide and the ternary U(VI)-hydroxide-peroxide systems have been
      studied using potentiometric and spectrophotometric data at 25  degrees C in a
      0.100 M tetramethylammonium nitrate medium. The data for the binary U(VI)
      hydroxide complexes were in good agreement with previous studies. In the ternary
      system two complexes were identified, [UO(2)(OH)(O(2))](-) and
      [(UO(2))(2)(OH)(O(2))(2)](-). Under our experimental conditions the former is
      predominant over a broad p[H(+)] region from 9.5 to 11.5, while the second is
      found in significant amounts at p[H(+)] < 10.5. The formation of the ternary
      peroxide complexes results in a strong increase in the molar absorptivity of the
      test solutions. The absorption spectrum for [(UO(2))(2)(OH)(O(2))(2)](-) was
      resolved into two components with peaks at 353 and 308 nm with molar absorptivity
      of 16200 and 20300 M(-1) cm(-1), respectively, suggesting that the electronic
      transitions are dipole allowed. The molar absorptivity of [(UO(2))(OH)(O(2))](-)
      at the same wave lengths are significantly lower, but still about one to two
      orders of magnitude larger than the values for UO(2)(2+)(aq) and the binary
      uranyl(VI) hydroxide complexes. It is of interest to note that
      [(UO(2))(OH)(O(2))](-) might be the building block in cluster compounds such as
      [UO(2)(OH)(O(2))](60)(60-) studied by Burns et al. (P. C. Burns, K. A. Kubatko,
      G. Sigmon, B. J. Fryer, J. E. Gagnon, M. R. Antonio and L. Soderholm, Angew.
      Chem. 2005, 117, 2173-2177). Speciation calculations using the known equilibrium
      constants for the U(vi) hydroxide and peroxide complexes show that the latter are
      important in alkaline solutions even at very low total concentrations of
      peroxide, suggesting that they may be involved when the uranium minerals Studtite
      and meta-Studtite are formed by alpha-radiolysis of water. Radiolysis will be
      much larger in repositories for spent nuclear fuel where hydrogen peroxide might
      contribute both to the corrosion of the fuel and to transport of uranium in a
      ground water system.

PMID- 21968964
TI  - Mantle cell lymphoma involvement of the pleura and tuberculous pleurisy with
      pulmonary tuberculosis: a case report and literature review.
AB  - A 78-year-old Japanese woman was admitted to our hospital for fever, dry cough,
      and right pleural effusion. She was diagnosed with mantle cell lymphoma (MCL) at
      73 years of age and was treated with carcinostatics, but MCL was refractory.
      Chest computed tomography (CT) on admission revealed a localized trabecular
      shadow in the middle lobe of the right lung and right pleural effusion with
      thickened visceral pleura. Right pleural effusion was exudative, lymphocytes were
      dominant, and adenosine deaminase isoenzymes were elevated. (18)F
      fluorodeoxyglucose positron emission tomography/CT revealed positive findings in
      the right thickened visceral pleura and right middle lobe. We suspected
      tuberculosis, but bronchoscopy revealed that the washing fluid was negative for
      Ziehl-Neelsen staining. Thoracoscopy under local anesthesia revealed redness on
      the parietal and visceral pleura and fibrin network. Pathological findings from
      pleural biopsy included granulomas, Langhans-type giant cells, and diffuse
      invasion of lymphocytes with atypical nuclei. Immunophenotypes were CD5(+), CD10(
      ), CD19(+), CD20(+), lambda(+), CD25(+) by flow cytometry and CD20(+), CD45RO(-),
      cyclin D1(+), bcl2(+), bcl6(-) by immunohistochemistry. We diagnosed MCL
      involvement of the pleura, and highly suspected tuberculous pleurisy. The patient
      received antituberculosis therapy with rifampicin, isoniazid, pyrazinamide, and
      ethambutol. After 4 weeks, culture of bronchoscopy washing fluid was positive for
      Mycobacterium tuberculosis. We diagnosed pulmonary tuberculosis. Patients with
      malignant lymphoma are vulnerable to tuberculosis. In addition to diagnosing MCL
      involvement of the pleura, it is important to consider the possibility of
      complication with tuberculosis.

PMID- 21968965
TI  - Assessing recovery of renal function after tenofovir disoproxil fumarate
      discontinuation.
AB  - Impaired renal function caused by tenofovir disoproxil fumarate (TDF) is
      considered reversible by discontinuing TDF administration, but there are
      occasional cases of incomplete recovery. We investigated the recovery of renal
      function after the discontinuation of TDF. Subjects comprised patients who had
      been started on TDF but in whom it was later discontinued because of impaired
      renal function. We investigated renal function until 96 weeks after the
      discontinuation of TDF, and the duration of TDF administration, up to May 2010.
      TDF was discontinued because of impaired renal function in 21 of 766 patients
      (2.7%). Following discontinuation, a significant recovery was seen in eGFR (p =
      0.003). The median duration of administration was 28 days (6-941 days) in 9
      patients whose eGFR recovered to pre-administration levels, 405 days (250-1,379)
      in 7 patients in whom mild recovery was seen, and 1,110 days (421-1,470) in 5
      patients in whom eGFR was much lower than at the time of discontinuation. A
      significant correlation was seen between the eGFR recovery rate and the duration
      of TDF administration. TDF administration was discontinued because of renal
      impairment in 2.7% of patients. The duration of TDF administration was short in
      patients whose renal function recovered to pre-administration levels, but
      patients in whom sufficient recovery was not seen after discontinuation had
      received TDF over long periods and included many whose renal function gradually
      declined, even after discontinuation. Recovery of renal function after
      discontinuation of TDF is likely affected by the duration of TDF administration.

PMID- 21968966
TI  - Nocardia elegans infection involving purulent arthritis in humans.
AB  - Nocardia elegans infection in humans is rare and is predominantly associated with
      pulmonary infections. We describe the first case of N. elegans infection
      associated with purulent arthritis in humans. The patient was a 66-year-old woman
      without underlying disease. She had swelling in her left ankle that was
      increasing in size, but it did not cause the patient substantial pain. Punctual
      discharge was collected for Gram staining and Kinyoun's acid-fast staining. The
      results of microscopic findings were suggestive of the genus Nocardia. The 16S
      rRNA sequence of the isolate was completely identical (100%) with that of N.
      elegans, indicating that the isolate was N. elegans. All the previously reported
      4 cases of N. elegans infection in humans were associated with respiratory
      infections; we present the first case of the infection involving purulent
      arthritis.

PMID- 21968967
TI  - Bactericidal activity of topical antiseptics and their gargles against Bordetella
      pertussis.
AB  - Bordetella pertussis is the etiological agent of whooping cough, a common cause
      of respiratory illness in both children and adults. In the present study, we
      investigated the bactericidal activity of four antiseptics-povidone-iodine (PVP
      I), benzethonium chloride (BEC), chlorhexidine gluconate (CHG) and benzalkonium
      chloride (BAC)-against B. pertussis ATCC9797 and clinical isolates. Among the
      topical antiseptics, PVP-I, BEC, and BAC, PVP-I and BAC in particular, showed
      high bactericidal activity, whereas CHG had low activity. PVP-I gargle also
      showed high bactericidal activity, similar to topical PVP-I. However, BEC gargle
      had low bactericidal activity. Our results indicate that topical PVP-I and BAC,
      and PVP-I gargle would be useful as effective antiseptics against B. pertussis.

PMID- 21968968
TI  - Purification of a novel RECQL5-SWI/SNF-RNAPII super complex.
AB  - RecQ helicases are members of an evolutionary conserved family of DNA helicases.
      They are homologous to the RecQ helicase of E. coli, the founding member of the
      family. These enzymes include gene products of disease-causing genes in Bloom,
      Werner, and Rothmund-Thomson syndrome. To date, these proteins have been
      implicated in many aspects of DNA metabolism, including DNA replication, repair,
      and recombination. We reported here that RECQL5, a newer member of the human RecQ
      helicase family, physically interacts with SWI/SNF complex and RNAPII core
      complex within the context of a super complex. RECQL5 was detected in the RNAPII
      holoenzyme but not in purified RNAPII core complex. Together, these data link
      RECQL5 to the assembly of the RNAPII transcription machinery and suggest that
      this helicase may have a regulatory role in RNAPII transcription or an RNAPII
      related process or processes.

PMID- 21968969
TI  - Apple extract induces increased epithelial resistance and claudin 4 expression in
      Caco-2 cells.
AB  - BACKGROUND: The small intestinal epithelium functions both to absorb nutrients,
      and to provide a barrier between the outside, luminal, world and the human body.
      One of the passageways across the intestinal epithelium is paracellular
      diffusion, which is controlled by the properties of tight junction complexes. We
      used a differentiated Caco-2 monolayer as a model for small intestinal epithelium
      to study the effect of crude apple extracts on paracellular permeability.
      RESULTS: Exposure of crude apple homogenate to the differentiated Caco-2 cells
      increased the paracellular resistance, determined as trans-epithelial electrical
      resistance (TEER). This increase was linearly related to the concentration of
      apple present. The TEER-enhancing effect of apple extract was due to factors
      mainly present in the cortex, and the induction was not inhibited by protein
      kinase inhibitors. Apple-induced resistance was accompanied by increased
      expression of several tight junction related genes, including claudin 4 (CLDN4).
      CONCLUSION: Crude apple extract induces a higher paracellular resistance in
      differentiated Caco-2 cells. Future research will determine whether these results
      can be extrapolated to human small intestinal epithelia.

PMID- 21968970
TI  - Diurnal pattern of intraocular pressure is affected by microgravity when measured
      in space with the pressure phosphene tonometer (PPT).
AB  - PURPOSE: This study was designed to evaluate the effect of microgravity on the
      diurnal variation of intraocular pressure (IOP). METHODS: IOPs were measured with
      the pressure phosphene tonometer in 1 subject (the first Korean astronaut) during
      spaceflight. IOPs were measured every 3 hours during day time (6 times per day)
      at 2 separate days in space with 3 repeated measurements at each time on both
      eyes. A total of 72 measurements were obtained during spaceflight. To obtain
      control IOP data, IOP was measured using the same protocol on ground before
      spaceflight. RESULTS: Mean IOP increased by 26.3% during spaceflight compared
      with that on ground [16.47 +/- 0.60 (SD) mm Hg vs. 13.04 +/- 0.74 mm Hg,
      P<0.001). The IOP elevation was maintained until Launch+8 days. There was no
      significant difference in IOP increase between right and left eyes (16.4 2 +/-
      0.65 mm Hg right eye vs. 16.53 +/- 0.56 mm Hg left eye). There was a different
      pattern of diurnal variation of IOP during spaceflight compared with that on
      ground. The IOP at 7 AM was the lowest under microgravity, whereas it was the
      highest on ground. The slope of the best fit line for diurnal IOP measures was
      0.0349 mm Hg/h (95% confidence interval: 0.0082-0.0616) under microgravity and 
      0.0294 mm Hg/h (95% confidence interval: -0.0063-0.0041) on ground. CONCLUSIONS:
      The study showed a different diurnal pattern of IOP under microgravity compared
      with that on ground. This result suggests that gravity and subsequent body fluid
      shift is one of the determining factors of IOP diurnal variation.

PMID- 21968972
TI  - Topographic differences in the age-related changes in the RNFL of normal eyes
      measured by Stratus optical coherence tomography letter.

PMID- 21968973
TI  - Genes differentially regulated by NKX2-3 in B cells between ulcerative colitis
      and Crohn's disease patients and possible involvement of EGR1.
AB  - Ulcerative colitis (UC) and Crohn's disease (CD) are two related yet different
      forms of chronic intestinal inflammation. We investigated the genes regulated by
      NKX2-3 in B cells from a UC patient by cDNA microarray and compared the results
      to those genes regulated by NKX2-3 in B cells from a CD patient. Genes regulated
      by NKX2-3 in B cells from UC were mainly involved in cell growth, inflammation,
      and immune response. Among the genes regulated by NKX2-3 in both UC and CD,
      expression of 145 genes was similarly altered and 34 genes was differentially
      affected by NKX2-3 knockdown. EGR1 was up-regulated in NKX2-3 knockdown B cells
      from UC while down-regulated in NKX2-3 knockdown B cells from CD. mRNA
      expressions of NKX2-3 and EGR1 were increased in diseased intestinal tissues from
      19 CD patients. NKX2-3 may play different roles in UC and CD pathogenesis by
      differential regulation of EGR1.

PMID- 21968974
TI  - Increased circulating levels of SDF-1 (CXCL12) in type 2 diabetic patients are
      correlated to disease state but are unrelated to polymorphism of the SDF-1beta
      gene in the Iranian population.
AB  - Several environmental and genetic factors are believed to influence the onset of
      diabetes and its complications. It has also been established that cytokines play
      a key role in the pathogenesis of type 2 diabetes. Previous studies have revealed
      that the polymorphism at the stromal-derived factor 1beta (SDF-1beta) 3'A
      regulates the expression of SDF-1 (CXCL12). This study was aimed to explore this
      polymorphism in parallel with SDF-1 serum levels in type 2 diabetic patients. In
      this assessment, peripheral blood samples were collected from 200 type 2 diabetic
      patients and 200 healthy controls. DNA was extracted, and a PCR-RFLP screening
      was applied to examine the SDF-1beta 3'A polymorphism. We also applied the ELISA
      technique to measure serum levels of SDF-1. Our results showed that there were no
      significant correlations between SDF-1beta 3'Alpha polymorphism in type 2
      diabetic patients when compared to controls. However, our results showed that the
      serum levels of SDF-1 were significantly increased in the patients when compared
      to controls. Based on the results of this study, we concluded that SDF-1beta
      3'Alpha polymorphism does not play a role in the pathogenesis of type 2 diabetes
      but that elevated serum levels of SDF-1 may be important for the etiology of type
      2 diabetes but are unrelated to the SDF-1beta 3'Alpha polymorphism.

PMID- 21968975
TI  - Infection of H69AR cells with retroviral particles harboring interfering RNAi
      significantly reduced the multidrug resistance of these small cell lung cancer
      cells.
AB  - Incubation of the drug-sensitive H69, a small cell lung cancer cell line, with
      increased concentrations of adriamycin yielded multidrug resistant (MDR) H69AR
      cells that over-express multidrug resistance-associated protein (MRP1). MRP1 co
      transports its substrate with glutathione (GSH), leading to lower intracellular
      GSH. In this report we tested whether depleting intracellular GSH in MRP1
      expressing cells could hyper-sensitize them to anticancer drugs or not. We have
      found that the GSH contents in MRP1-expressing cells are significantly lower than
      their corresponding control cells. The treatment with MRP1 substrate verapamil or
      the GSH synthetase inhibitor buthionine sulfoxi-mine significantly reduced the
      intracellular GSH contents in MRP1-expressing cells. Interestingly, depleting
      intracellular GSH contents can hyper-sensitize the MRP1-cDNA transfected BHK
      cells to daunomycin, but not the adriamycin-selected H69AR cells. Further
      analyses indicated that anti-apoptotic factor Bcl2 might be a factor responsible
      for the fact that depleting intracellular GSH could not hyper-sensitize H69AR
      cells to daunomycin. We hypothesized that knocking down the expression of Bcl2
      could hyper-sensitize H69AR cells to daunomycin. Interestingly, infection of
      H69AR cells with retroviral particles harboring Bcl2 interfering RNAi not only
      reduced the expression of Bcl2, but also many factors that contribute to MDR,
      such as Bcl-xl, MRP1 and ABCC3, etc., leading to the MDR H69AR cells more
      sensitive to daunomycin than the parental H69 cell. Thus, although the mechanisms
      of the down-regulation of the genes contributing to MDR remain to be elucidated,
      retroviral particles harboring Bcl2 interfering RNAi could be used as an
      alternative way to sensitize the MDR cancer cells to anticancer drugs.

PMID- 21968976
TI  - Automated hydrophobic interaction chromatography column selection for use in
      protein purification.
AB  - In contrast to other chromatographic methods for purifying proteins (e.g. gel
      filtration, affinity, and ion exchange), hydrophobic interaction chromatography
      (HIC) commonly requires experimental determination (referred to as screening or
      "scouting") in order to select the most suitable chromatographic medium for
      purifying a given protein (1). The method presented here describes an automated
      approach to scouting for an optimal HIC media to be used in protein purification.
      HIC separates proteins and other biomolecules from a crude lysate based on
      differences in hydrophobicity. Similar to affinity chromatography (AC) and ion
      exchange chromatography (IEX), HIC is capable of concentrating the protein of
      interest as it progresses through the chromatographic process. Proteins best
      suited for purification by HIC include those with hydrophobic surface regions and
      able to withstand exposure to salt concentrations in excess of 2 M ammonium
      sulfate ((NH(4;))(2;)SO(4;)). HIC is often chosen as a purification method for
      proteins lacking an affinity tag, and thus unsuitable for AC, and when IEX fails
      to provide adequate purification. Hydrophobic moieties on the protein surface
      temporarily bind to a nonpolar ligand coupled to an inert, immobile matrix. The
      interaction between protein and ligand are highly dependent on the salt
      concentration of the buffer flowing through the chromatography column, with high
      ionic concentrations strengthening the protein-ligand interaction and making the
      protein immobile (i.e. bound inside the column) (2). As salt concentrations
      decrease, the protein-ligand interaction dissipates, the protein again becomes
      mobile and elutes from the column. Several HIC media are commercially available
      in pre-packed columns, each containing one of several hydrophobic ligands (e.g. S
      butyl, butyl, octyl, and phenyl) cross-linked at varying densities to agarose
      beads of a specific diameter (3). Automated column scouting allows for an
      efficient approach for determining which HIC media should be employed for future,
      more exhaustive optimization experiments and protein purification runs (4). The
      specific protein being purified here is recombinant green fluorescent protein
      (GFP); however, the approach may be adapted for purifying other proteins with one
      or more hydrophobic surface regions. GFP serves as a useful model protein, due to
      its stability, unique light absorbance peak at 397 nm, and fluorescence when
      exposed to UV light (5). Bacterial lysate containing wild type GFP was prepared
      in a high-salt buffer, loaded into a Bio-Rad DuoFlow medium pressure liquid
      chromatography system, and adsorbed to HiTrap HIC columns containing different
      HIC media. The protein was eluted from the columns and analyzed by in-line and
      post-run detection methods. Buffer blending, dynamic sample loop injection,
      sequential column selection, multi-wavelength analysis, and split fraction eluate
      collection increased the functionality of the system and reproducibility of the
      experimental approach.

PMID- 21968977
TI  - Downregulation of the tumour suppressor p16INK4A contributes to the polarisation
      of human macrophages toward an adipose tissue macrophage (ATM)-like phenotype.
AB  - AIMS/HYPOTHESIS: Human adipose tissue macrophages (ATMs) display an alternatively
      activated (M2) phenotype, but are still able to produce excessive inflammatory
      mediators. However, the processes driving this particular ATM phenotype are not
      understood. Genome-wide association studies associated the CDKN2A locus, encoding
      the tumour suppressor p16(INK4A), with the development of type 2 diabetes. In the
      present study, p16(INK4A) levels in human ATMs and the role of p16(INK4A) in
      acquiring the ATM phenotype were assessed. METHODS: Gene expression of p16 (
      INK4A ) in ATMs was analysed and compared with that in monocyte-derived
      macrophages (MDMs) from obese patients or with macrophages from human
      atherosclerotic plaques (AMs). Additionally, p16(INK4A) levels were studied
      during macrophage differentiation and polarisation of monocytes isolated from
      healthy donors. The role of p16(INK4A) in MDMs from healthy donors was
      investigated by small interfering (si)RNA-mediated silencing or adenovirus
      mediated overproduction of p16(INK4A). RESULTS: Compared with MDMs and AMs, ATMs
      from obese patients expressed lower levels of p16 ( INK4A ). In vitro, IL-4
      induced M2 polarisation resulted in lower p16(INK4A) protein levels after
      differentiation of monocytes from healthy donors in macrophages. Silencing of
      p16(INK4A) in MDMs mediated by siRNA increased the expression of M2 marker genes
      and enhanced the response to lipopolysaccharide (LPS), to give a phenotype
      resembling that of ATM. By contrast, adenovirus-mediated overproduction of
      p16(INK4A) in MDMs diminished M2 marker gene expression and the response to LPS.
      Western blot analysis revealed that p16(INK4A) overproduction inhibits LPS- and
      palmitate-induced Toll-like receptor 4 (TLR4)-nuclear factor of kappa light
      polypeptide gene enhancer in B cells (NF-kappaB) signalling.
      CONCLUSIONS/INTERPRETATION: These results show that p16(INK4A) inhibits the
      acquisition of the ATM phenotype. The age-related increase in p16(INK4A) level
      may thus influence normal ATM function and contribute to type 2 diabetes risk.

PMID- 21968978
TI  - Fetal opercular cavernous angioma causing cerebral cleft: contralateral primitive
      vascular anomaly and subicular dysgenesis.
AB  - We describe a 22-week female fetus after pregnancy was terminated because of
      fetal magnetic resonance imaging showing a large left cerebral hemispheric cleft
      suggestive of porencephaly or schizencephaly. Postmortem examination revealed a
      large cavernous angioma of the left opercular region with evidence of previous
      hemorrhage and extensive cerebral infarction. In the right hemisphere, another
      vascular malformation within the frontal germinal matrix consisted of an
      aggregate of primitive vessels not yet canalized. Selective dysgenesis of the
      right subiculum also was demonstrated. This case illustrates not only a severe
      encephaloclastic effect of cavernous angioma in fetal brain but also the
      importance of fetal autopsy to help correlate and explain fetal neuroimaging.
      Potential future prenatal treatment of fetal angiomata requires precise in utero
      diagnosis.

PMID- 21968979
TI  - Prolonged elevation of serum neuron-specific enolase in children after clinical
      diagnosis of brain death.
AB  - To elucidate the time course of neuronal cell death after the clinical criteria
      for brain death are met, the authors reviewed serial changes of serum neuron
      specific enolase levels in 3 children (age range, 3-15 years) clinically
      diagnosed as brain dead due to cardiopulmonary arrest. All patients survived for
      more than 2 months after brain death. Children with brain death had higher peak
      neuron-specific enolase values (1069-2849 ng/mL) than did 3 control children (256
      1800 ng/mL) who did not become brain dead but had poor neurological outcome (1
      death, 2 vegetative state) after cardiopulmonary arrest. A major finding is that
      children with brain death showed persistent elevation of neuron-specific enolase
      at 4 weeks (>400 ng/mL) and 8 weeks (>50 ng/mL) after cardiopulmonary arrest, in
      comparison with 2 surviving patients without brain death (<50 ng/mL at 4 weeks).
      This prolonged elevation of neuron-specific enolase suggests that total brain
      necrosis might not be present at the time of clinical diagnosis of brain death.

PMID- 21968980
TI  - Developmental and behavior problems predict parenting stress in young children
      with global delay.
AB  - To identify parent-reported symptoms that predict parenting stress in
      preschoolers with global developmental delay, 201 parents/guardians of 142 boys
      and 59 girls with global delay, mean age 39.1 months (range, 18 to 63 months)
      were studied retrospectively. Parents completed the following: (a) a
      semistructured interview; (b) the Child Development Inventory, (c) Child Behavior
      Checklist 1&frac12;-5, and the (d) Parenting Stress Index-Short Form. Forty-two
      percent of parents described clinically significant parenting stress (>= 85th
      percentile). The Parenting Stress Index-Short Form subscales Difficult Child and
      Parent-Child Dysfunctional Interactions were elevated. Parental stress increased
      with higher gross motor development and decreased as social and fine-motor ratios
      increased. Furthermore, stress increased when parents reported higher levels on
      the Emotionally Reactive and Withdrawn scale scores and when parents reported
      Pervasive Developmental and Oppositional Defiant Problems. In mobile children
      with global delay, behavior problems predict parenting stress.

PMID- 21968981
TI  - Long-term diffusion impairment of cerebral white matter in a degenerative disease
      of the central and peripheral nervous system: reflection of chronic
      excitotoxicity?
AB  - The authors report an abnormal prolonged restricted magnetic resonance imaging
      (MRI) proton diffusion that persisted for more than 2 years in a 6.5-year-old boy
      with a progressive neurological disease characterized by developmental
      retardation, peripheral polyneuropathy, and bilateral optical nerve atrophy. The
      long-term restricted magnetic resonance imaging proton diffusion observed in
      diffusion-weighted magnetic resonance images indicates chronic metabolic tissue
      impairment in the affected white matter, whereas measurable lactate accumulation
      in proton magnetic resonance spectroscopy was absent, and no respiratory complex
      abnormality was found in muscle tissue. These findings are suggestive of a
      chronically disturbed regulation of energy supply triggering a "slow onset"
      excitotoxicity, causing chronic hypoxia and leading to slow cell death as has
      been postulated in certain neurodegenerative processes.

PMID- 21968982
TI  - Miller-Fisher syndrome in association with enterovirus infection.
AB  - Miller-Fisher is a rare syndrome of childhood that presents with external
      ophthalmoplegia, ataxia, and areflexia. It has been mainly associated with a
      preceding Campylobacter infection and less commonly with other bacterial or viral
      infections. This report describes, for the first time, a child with Miller-Fisher
      syndrome and documented Enterovirus infection, as it was proven by the isolation
      of Enterovirus from cerebrospinal fluid by polymerase chain reaction testing.

PMID- 21968983
TI  - American childhood football as a possible risk factor for cerebral infarction.
AB  - Three adolescent football players who had ischemic stroke associated with
      football practice and play are described. The literature on stroke associated
      with childhood sports and football in particular is reviewed, and the multiple
      mechanisms by which football can contribute to ischemic stroke are discussed.

PMID- 21968984
TI  - The demographic, clinical, and magnetic resonance imaging (MRI) features of
      transverse myelitis in children.
AB  - The authors collected demographic, clinical, and neuroimaging data prospectively
      on 38 children with transverse myelitis. One child died during the illness. The
      female:male ratio was 1.2:1 for children under age 10 years and 2.6:1 over age 10
      years. Twenty-eight (74%) reported a prodromal event. Twenty-two patients (58%)
      had longitudinally extensive transverse myelitis, 9 (24%) had focal lesions, and
      5 (13%) had both. Twenty of 33 with brain imaging (61%) had brain lesions; 7
      fulfilled McDonald criteria for dissemination in space. Seven of 22 (36%) tested
      had cerebrospinal fluid oligoclonal banding, 6 of whom had brain lesions. Serum
      neuromyelitis optica IgG antibodies were absent in all 20 of the children for
      whom this test was available. At follow-up (mean 3.2 +/- 2.0 years), 16% are
      wheelchair-dependent, 22% have persisting bladder dysfunction, and 13% have been
      diagnosed with multiple sclerosis.

PMID- 21968985
TI  - Pulmonary Lymphomatoid Granulomatosis: Report of A Case and Review of Literature.
AB  - Lymphomatoid granulomatosis (LYG) is a rare angiocentric lymphoproliferative
      process predominantly affecting the lung. The diagnosis of this condition is
      often difficult as the physical signs, history, chest x-ray, and routine
      laboratory investigations are usually non-specific. Nevertheless, it is important
      to establish a tissue diagnosis, as this lymphoproliferative disorder can be
      refractory to treatment and even progress to overt lymphoma. We report a case of
      pulmonary LYG in a 52-year old Nigerian man of Ibo extraction treated in our
      centre in 2001 and followed up for a year. The difficulty in making diagnosis is
      highlighted and treatment modality discussed.

PMID- 21968986
TI  - Focus on cell cycle and DNA damage.

PMID- 21968987
TI  - UK Parliament comments on peer review.

PMID- 21968988
TI  - The centrosome cycle: Centriole biogenesis, duplication and inherent asymmetries.
AB  - Centrosomes are microtubule-organizing centres of animal cells. They influence
      the morphology of the microtubule cytoskeleton, function as the base for the
      primary cilium and serve as a nexus for important signalling pathways. At the
      core of a typical centrosome are two cylindrical microtubule-based structures
      termed centrioles, which recruit a matrix of associated pericentriolar material.
      Cells begin the cell cycle with exactly one centrosome, and the duplication of
      centrioles is constrained such that it occurs only once per cell cycle and at a
      specific site in the cell. As a result of this duplication mechanism, the two
      centrioles differ in age and maturity, and thus have different functions; for
      example, the older of the two centrioles can initiate the formation of a ciliary
      axoneme. We discuss spatial aspects of the centrosome duplication cycle, the
      mechanism of centriole assembly and the possible consequences of the inherent
      asymmetry of centrioles and centrosomes.

PMID- 21968989
TI  - More than just a focus: The chromatin response to DNA damage and its role in
      genome integrity maintenance.
AB  - Following the discovery in 1998 of gamma-H2AX, the first histone modification
      induced by DNA damage, interest in the changes to chromatin induced by DNA damage
      has exploded, and a vast amount of information has been generated. However, there
      has been a discrepancy between our rapidly advancing knowledge of how chromatin
      responds to DNA damage and the understanding of why cells mobilize large segments
      of chromatin to protect the genome against destabilizing effects posed by tiny
      DNA lesions. Recent research has provided insights into these issues and suggests
      that chromatin responses induced by DNA damage are not simply the accumulation of
      'nuclear foci' but are mechanisms required to guard genome integrity.

PMID- 21968990
TI  - Cohesin: a catenase with separate entry and exit gates?
AB  - Cohesin confers both intrachromatid and interchromatid cohesion through formation
      of a tripartite ring within which DNA is thought to be entrapped. Here, I discuss
      what is known about the four stages of the cohesin ring cycle using the ring
      model as an intellectual framework. I postulate that cohesin loading onto
      chromosomes, catalysed by a separate complex called kollerin, is mediated by the
      entry of DNA into cohesin rings, whereas dissociation, catalysed by Wapl and
      several other cohesin subunits (an activity that will be called releasin here),
      is mediated by the subsequent exit of DNA. I suggest that the ring's entry and
      exit gates may be separate, with the former and latter taking place at Smc1-Smc3
      and Smc3-kleisin interfaces, respectively. Establishment of cohesion during S
      phase involves neutralization of releasin through acetylation of Smc3 at a site
      close to the putative exit gate of DNA, which locks rings shut until opened
      irreversibly by kleisin cleavage through the action of separase, an event that
      triggers the metaphase to anaphase transition.

PMID- 21968991
TI  - A brief history of error.
AB  - The spindle checkpoint monitors chromosome alignment on the mitotic and meiotic
      spindle. When the checkpoint detects errors, it arrests progress of the cell
      cycle while it attempts to correct the mistakes. This perspective will present a
      brief history summarizing what we know about the checkpoint, and a list of
      questions we must answer before we understand it.

PMID- 21968992
TI  - Spindle positioning: going against the actin flow.
AB  - Successful completion of meiosis in vertebrate oocytes requires the localization
      and maintenance of the meiotic spindle at the cell cortex. Arp2/3-nucleated actin
      filaments are now shown to flow away from the cortex overlying the spindle,
      resulting in cytoplasmic streaming, which maintains the spindle in its asymmetric
      position.

PMID- 21968997
TI  - NF-kappaB controls energy homeostasis and metabolic adaptation by upregulating
      mitochondrial respiration.
AB  - Cell proliferation is a metabolically demanding process. It requires active
      reprogramming of cellular bioenergetic pathways towards glucose metabolism to
      support anabolic growth. NF-kappaB/Rel transcription factors coordinate many of
      the signals that drive proliferation during immunity, inflammation and
      oncogenesis, but whether NF-kappaB regulates the metabolic reprogramming required
      for cell division during these processes is unknown. Here, we report that NF
      kappaB organizes energy metabolism networks by controlling the balance between
      the utilization of glycolysis and mitochondrial respiration. NF-kappaB inhibition
      causes cellular reprogramming to aerobic glycolysis under basal conditions and
      induces necrosis on glucose starvation. The metabolic reorganization that results
      from NF-kappaB inhibition overcomes the requirement for tumour suppressor
      mutation in oncogenic transformation and impairs metabolic adaptation in cancer
      in vivo. This NF-kappaB-dependent metabolic pathway involves stimulation of
      oxidative phosphorylation through upregulation of mitochondrial synthesis of
      cytochrome c oxidase 2 (SCO2; ref. ). Our findings identify NF-kappaB as a
      physiological regulator of mitochondrial respiration and establish a role for NF
      kappaB in metabolic adaptation in normal cells and cancer.

PMID- 21968999
TI  - Chronological aging is associated with biophysical and chemical changes in the
      capsule of Cryptococcus neoformans.
AB  - Does the age of a microbial cell affect its virulence factors? To our knowledge,
      this question has not been addressed previously, but the answer is of great
      relevance for chronic infections where microbial cells persist and age in hosts.
      Cryptococcus neoformans is an encapsulated human-pathogenic fungus notorious for
      causing chronic infections where cells of variable age persist in tissue. The
      major virulence factor for C. neoformans is a polysaccharide (PS) capsule. To
      understand how chronological age could impact the cryptococcal capsule
      properties, we compared the elastic properties, permeabilities, zeta potentials,
      and glycosidic compositions of capsules from young and old cells and found
      significant differences in all parameters measured. Changes in capsular
      properties were paralleled by changes in PS molecular mass and density, as well
      as modified antigenic density and antiphagocytic properties. Remarkably,
      chronological aging under stationary-phase growth conditions was associated with
      the expression of alpha-1,3-glucans in the capsule, indicating a new structural
      capsular component. Our results establish that cryptococcal capsules are highly
      dynamic structures that change dramatically with chronological aging under
      prolonged stationary-phase growth conditions. Changes associated with cellular
      aging in chronic infections could contribute to the remarkable capacity of this
      fungus to persist in tissues by generating phenotypically and antigenically
      different capsules.

PMID- 21969000
TI  - Naturally acquired immune responses to Plasmodium falciparum sexual stage
      antigens Pfs48/45 and Pfs230 in an area of seasonal transmission.
AB  - Acquisition of immunity to Plasmodium falciparum sexual stages is a key
      determinant for reducing human-mosquito transmission by preventing the
      fertilization and the development of the parasite in the mosquito midgut.
      Naturally acquired immunity against sexual stages may therefore form the basis
      for the development of transmission-blocking vaccines, but studies conducted to
      date offer little in the way of consistent findings. Here, we describe the
      acquisition of antigametocyte immune responses in malaria-exposed individuals in
      Burkina Faso. A total of 719 blood samples were collected in a series of three
      cross-sectional surveys at the start, peak, and end of the wet season. The
      seroprevalence of antibodies with specificity for the sexual stage antigens
      Pfs48/45 and Pfs230 was 2-fold lower (22 to 28%) than that for an asexual blood
      stage antigen glutamate-rich protein (GLURP) (65%) or for the preerythrocytic
      stage antigen circumsporozoite protein (CSP) (54%). The youngest children
      responded at frequencies similar to those for all four antigens but, in contrast
      with the immune responses to GLURP and CSP that increased with age independently
      of season and area of residence, there was no evidence for a clear age dependence
      of responses to Pfs48/45 and Pfs230. Anti-Pfs230 antibodies were most prevalent
      at the peak of the wet season (P < 0.001). Our findings suggest that naturally
      acquired immunity against Pfs48/45 and Pfs230 is a function of recent exposure
      rather than of cumulative exposure to gametocytes.

PMID- 21969001
TI  - Functional promoter haplotypes of interleukin-18 condition susceptibility to
      severe malarial anemia and childhood mortality.
AB  - Severe malarial anemia (SMA) is a leading cause of morbidity and mortality in
      children residing in regions where Plasmodium falciparum transmission is
      holoendemic. Although largely unexplored in children with SMA, interleukin-18 (IL
      18) is important for regulating innate and acquired immunity in inflammatory and
      infectious diseases. As such, we selected two functional single-nucleotide
      polymorphisms (SNPs) in the IL-18 promoter (-137G->C [rs187238] and -607C->A
      [rs1946518]) whose haplotypes encompass significant genetic variation due to the
      presence of strong linkage disequilibrium among these variants. The relationship
      between the genotypes/haplotypes, SMA (hemoglobin [Hb], <5.0 g/dl], and
      longitudinal clinical outcomes were then investigated in Kenyan children (n =
      719). Multivariate logistic regression analyses controlling for age, gender,
      sickle cell trait, glucose-6-phosphate dehydrogenase (G6PD) deficiency, HIV-1,
      and bacteremia revealed that carriage of the -607AA genotype was associated with
      protection against SMA (odds ratio [OR] = 0.440 [95% confidence interval {CI} =
      0.21 to 0.90], P = 0.031) in children with acute infection. In contrast, carriers
      of the -137G/-607C (GC) haplotype had increased susceptibility to SMA (OR = 2.050
      [95% CI = 1.04 to 4.05], P = 0.039). Measurement of IL-18 gene expression in
      peripheral blood leukocytes demonstrated that elevated IL-18 transcripts were
      associated with reduced hemoglobin concentrations (rho = -0.293, P = 0.010) and
      that carriers of the "susceptible" GC haplotype had elevated IL-18 transcripts (P
      = 0.026). Longitudinal investigation of clinical outcomes over a 3-year follow-up
      period revealed that carriers of the rare CC haplotype (~1% frequency) had 5.76
      times higher mortality than noncarriers (P = 0.001). Results presented here
      demonstrate that IL-18 promoter haplotypes that condition elevated IL-18 gene
      products during acute infection are associated with increased risk of SMA.
      Furthermore, carriage of the rare CC haplotype significantly increases the risk
      of childhood mortality.

PMID- 21969002
TI  - Role of the Yersinia pestis Ail protein in preventing a protective
      polymorphonuclear leukocyte response during bubonic plague.
AB  - The ability of Yersinia pestis to forestall the mammalian innate immune response
      is a fundamental aspect of plague pathogenesis. In this study, we examined the
      effect of Ail, a 17-kDa outer membrane protein that protects Y. pestis against
      complement-mediated lysis, on bubonic plague pathogenesis in mice and rats. The
      Y. pestis ail mutant was attenuated for virulence in both rodent models. The
      attenuation was greater in rats than in mice, which correlates with the ability
      of normal rat serum, but not mouse serum, to kill ail-negative Y. pestis in
      vitro. Intradermal infection with the ail mutant resulted in an atypical,
      subacute form of bubonic plague associated with extensive recruitment of
      polymorphonuclear leukocytes (PMN or neutrophils) to the site of infection in the
      draining lymph node and the formation of large purulent abscesses that contained
      the bacteria. Systemic spread and mortality were greatly attenuated, however, and
      a productive adaptive immune response was generated after high-dose challenge, as
      evidenced by high serum antibody levels against Y. pestis F1 antigen. The Y.
      pestis Ail protein is an important bubonic plague virulence factor that inhibits
      the innate immune response, in particular the recruitment of a protective PMN
      response to the infected lymph node.

PMID- 21969004
TI  - Hepatitis B virus mutants associated with hepatitis B surface antigen loss:
      chicken or egg?

PMID- 21969003
TI  - Live attenuated Shigella dysenteriae type 1 vaccine strains overexpressing shiga
      toxin B subunit.
AB  - Shigella dysenteriae serotype 1 (S. dysenteriae 1) is unique among the Shigella
      species and serotypes in the expression of Shiga toxin which contributes to more
      severe disease sequelae and the ability to cause explosive outbreaks and
      pandemics. S. dysenteriae 1 shares characteristics with other Shigella species,
      including the capability of causing clinical illness with a very low inoculum (10
      to 100 CFU) and resistance to multiple antibiotics, underscoring the need for
      efficacious vaccines and therapeutics. Following the demonstration of  the
      successful attenuating capacity of deletion mutations in the guaBA operon in S.
      flexneri 2a vaccine strains in clinical studies, we developed a series of S.
      dysenteriae 1 vaccine candidates containing the fundamental attenuating mutation
      in guaBA. All strains are devoid of Shiga toxin activity by specific deletion of
      the gene encoding the StxA subunit, which encodes enzymatic activity. The StxB
      subunit was overexpressed in several derivatives by either plasmid-based
      constructs or chromosomal manipulation to include a strong promoter. All strains
      are attenuated for growth in vitro in the HeLa cell assay and for plaque
      formation and were safe in the Sereny test and immunogenic in the guinea pigs.
      Each strain induced robust serum and mucosal anti-S. dysenteriae 1
      lipopolysaccharide (LPS) responses and protected against wild-type challenge. Two
      strains engineered to overexpress StxB induced high titers of Shiga toxin
      neutralizing antibodies. These candidates demonstrate the potential for a live
      attenuated vaccine to protect against disease caused by S. dysenteriae 1 and
      potentially to protect against the toxic effects of other Shiga toxin 1
      expressing pathogens.

PMID- 21969005
TI  - Assessment of willow (Salix sp.) as a woody heavy metal accumulator: field survey
      and in vivo X-ray analyses.
AB  - Trees that accumulate metals are important plants for restoring contaminated soil
      because of their high biomass. In our previous study, we discovered that Salix
      miyabeana has the capability to take up high levels of Cd, and identified the
      several accumulation sites of the endogenous metals in the leaf parts of plants.
      To analyze the detailed localization of Cd in apoplastic and symplastic
      compartments in S. miyabeana, synchrotron radiation-based micro X-ray
      fluorescence (SR-MU-XRF) analysis and micro X-ray absorption near edge structure
      (MU-XANES) measurements were performed on beam line 37XU of the SPring-8 (Hyogo,
      Japan). The two-dimensional metal distribution of segments of young stems was
      obtained by MU-XRF with approximately 2 MUm(2) X-ray beams and showed the
      predominant localization of Cd in the apoplastic region. MU-XANES analyses
      suggest that the apoplastic detoxification of Cd in willow depends on Cd-oxygen,
      but not on Cd-sulfur, interaction. S. miyabeana growing near an old mining site
      in Japan was then examined to evaluate the metal accumulating ability of this
      plant in the field. The metal concentration in the leaves of the plants was
      compared to that in the soil and enrichment factors (EFs) were calculated for Cu,
      Zn, Cd and Pb. Results showed efficient removal of Cd and Zn from the
      contaminated sites by the willow plants. In order to discuss the combined and
      long-term effect of multiple heavy metals on S. miyabeana grown in soil, variable
      pressure scanning electron microscopy fitted with energy dispersive X-ray
      analysis (VPSEM-EDX) and SR-MU-XRF was used to characterize the serration of
      leaves. The combination of 2D elemental images revealed metal accumulation in the
      tip cells in serrations without any exudation of heavy metals from the
      hydathodes.

PMID- 21969006
TI  - Synergistic effects of arsenic trioxide and silibinin on apoptosis and invasion
      in human glioblastoma U87MG cell line.
AB  - Patients with glioblastoma multiforme (GBM) have poor therapeutic outcomes
      despite their current therapy. In an attempt to increase the efficacy of therapy
      for GBM, we studied the efficacy of arsenic trioxide (ATO), a newly introduced
      treatment for glioma, combined with silibinin, a natural polyphenolic flavonoid,
      in the GBM cell line, U87MG. The combination therapy synergically inhibited
      metabolic activity, cell proliferation, and gelatinase A and B activities; it
      also increased apoptosis. Additionally, it decreased the mRNA level of cathepsin
      B, uPA, matrix metalloproteinase-2 and 9, membrane type 1-MMP, survivin, BCL2,
      CA9; it increased mRNA level of caspase-3. Altogether, these results showed that
      ATO and silibinin in some cases improved and/or complemented the anticancer
      effects. This study may supply insight into the design of new combination cancer
      therapies to cells intrinsically less sensitive to routine therapies and
      suggested a new combination therapy for the highly invasive human glioma
      treatment.

PMID- 21969008
TI  - Induction of vascular GTP-cyclohydrolase I and endogenous tetrahydrobiopterin
      synthesis protect against inflammation-induced endothelial dysfunction in human
      atherosclerosis.
AB  - BACKGROUND: The endothelial nitric oxide synthase cofactor tetrahydrobiopterin
      (BH4) is essential for maintenance of enzymatic function. We hypothesized that
      induction of BH4 synthesis might be an endothelial defense mechanism against
      inflammation in vascular disease states. METHODS AND RESULTS: In Study 1, 20
      healthy individuals were randomized to receive Salmonella typhi vaccine (a model
      of acute inflammation) or placebo in a double-blind study. Vaccination increased
      circulating BH4 and interleukin 6 and induced endothelial dysfunction (as
      evaluated by brachial artery flow-mediated dilation) after 8 hours. In Study 2, a
      functional haplotype (X haplotype) in the GCH1 gene, encoding GTP-cyclohydrolase
      I, the rate-limiting enzyme in biopterin biosynthesis, was associated with
      endothelial dysfunction in the presence of high-sensitivity C-reactive protein in
      440 coronary artery disease patients. In Study 3, 10 patients with coronary
      artery disease homozygotes for the GCH1 X haplotype (XX) and 40 without the
      haplotype (OO) underwent S Typhi vaccination. XX patients were unable to increase
      plasma BH4 and had a greater reduction of flow-mediated dilation than OO
      patients. In Study 4, vessel segments from 19 patients undergoing coronary bypass
      surgery were incubated with or without cytokines (interleukin-6/tumor necrosis
      factor-alpha/lipopolysaccharide) for 24 hours. Cytokine stimulation upregulated
      GCH1 expression, increased vascular BH4, and improved vasorelaxation in response
      to acetylcholine, which was inhibited by the GTP-cyclohydrolase inhibitor 2,4
      diamino-6-hydroxypyrimidine. CONCLUSIONS: The ability to increase vascular GCH1
      expression and BH4 synthesis in response to inflammation preserves endothelial
      function in inflammatory states. These novel findings identify BH4 as a vascular
      defense mechanism against inflammation-induced endothelial dysfunction.

PMID- 21969009
TI  - Long-term follow-up of participants with heart failure in the antihypertensive
      and lipid-lowering treatment to prevent heart attack trial (ALLHAT).
AB  - BACKGROUND: In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart
      Attack Trial (ALLHAT), a randomized, double-blind, practice-based, active
      control, comparative effectiveness trial in high-risk hypertensive participants,
      risk of new-onset heart failure (HF) was higher in the amlodipine (2.5-10 mg/d)
      and lisinopril (10-40 mg/d) arms compared with the chlorthalidone (12.5-25 mg/d)
      arm. Similar to other studies, mortality rates following new-onset HF were very
      high (>=50% at 5 years), and were similar across randomized treatment arms. After
      the randomized phase of the trial ended in 2002, outcomes were determined from
      administrative databases. METHODS AND RESULTS: With the use of national
      databases, posttrial follow-up mortality through 2006 was obtained on
      participants who developed new-onset HF during the randomized (in-trial) phase of
      ALLHAT. Mean follow-up for the entire period was 8.9 years. Of 1761 participants
      with incident HF in-trial, 1348 died. Post-HF all-cause mortality was similar
      across treatment groups, with adjusted hazard ratios (95% confidence intervals)
      of 0.95 (0.81-1.12) and 1.05 (0.89-1.25), respectively, for amlodipine and
      lisinopril compared with chlorthalidone, and 10-year adjusted rates of 86%, 87%,
      and 83%, respectively. All-cause mortality rates were also similar among those
      with reduced ejection fractions (84%) and preserved ejection fractions (81%),
      with no significant differences by randomized treatment arm. CONCLUSIONS: Once HF
      develops, risk of death is high and consistent across randomized treatment
      groups. Measures to prevent the development of HF, especially blood pressure
      control, must be a priority if mortality associated with the development of HF is
      to be addressed. Clinical Trial Registration- http://www.clinicaltrials.gov.
      Unique identifier: NCT00000542.

PMID- 21969010
TI  - Primary outcomes for resuscitation science studies: a consensus statement from
      the American Heart Association.
AB  - BACKGROUND AND PURPOSE: The guidelines presented in this consensus statement are
      intended to serve researchers, clinicians, reviewers, and regulators in the
      selection of the most appropriate primary outcome for a clinical trial of cardiac
      arrest therapies. The American Heart Association guidelines for the treatment of
      cardiac arrest depend on high-quality clinical trials, which depend on the
      selection of a meaningful primary outcome. Because this selection process has
      been the subject of much controversy, a consensus conference was convened with
      national and international experts, the National Institutes of Health, and the US
      Food and Drug Administration. METHODS: The Research Working Group of the American
      Heart Association Emergency Cardiovascular Care Committee nominated subject
      leaders, conference attendees, and writing group members on the basis of their
      expertise in clinical trials and a diverse perspective of cardiovascular and
      neurological outcomes (see the online-only Data Supplement). Approval was
      obtained from the Emergency Cardiovascular Care Committee and the American Heart
      Association Manuscript Oversight Committee. Preconference position papers were
      circulated for review; the conference was held; and postconference consensus
      documents were circulated for review and comments were invited from experts,
      conference attendees, and writing group members. Discussions focused on (1) when
      after cardiac arrest the measurement time point should occur; (2) what
      cardiovascular, neurological, and other physiology should be assessed; and (3)
      the costs associated with various end points. The final document underwent
      extensive revision and peer review by the Emergency Cardiovascular Care
      Committee, the American Heart Association Science Advisory and Coordinating
      Committee, and oversight committees. RESULTS: There was consensus that no single
      primary outcome is appropriate for all studies of cardiac arrest. The best
      outcome measure is the pairing of a time point and physiological condition that
      will best answer the question under study. Conference participants were asked to
      assign an outcome to each of 4 hypothetical cases; however, there was not
      complete agreement on an ideal outcome measure even after extensive discussion
      and debate. There was general consensus that it is appropriate for earlier
      studies to enroll fewer patients and to use earlier time points such as return of
      spontaneous circulation, simple "alive versus dead," hospital mortality, or a
      hemodynamic parameter. For larger studies, a longer time point after arrest
      should be considered because neurological assessments fluctuate for at least 90
      days after arrest. For large trials designed to have a major impact on public
      health policy, longer-term end points such as 90 days coupled with neurocognitive
      and quality-of-life assessments should be considered, as should the additional
      costs of this approach. For studies that will require regulatory oversight, early
      discussions with regulatory agencies are strongly advised. For neurological
      assessment of post-cardiac arrest patients, researchers may wish to use the
      Cerebral Performance Categories or modified Rankin Scale for global outcomes.
      CONCLUSIONS: Although there is no single recommended outcome measure for trials
      of cardiac arrest care, the simple Cerebral Performance Categories or modified
      Rankin Scale after 90 days provides a reasonable outcome parameter for many
      trials. The lack of an easy-to-administer neurological functional outcome measure
      that is well validated in post-cardiac arrest patients is a major limitation to
      the field and should be a high priority for future development.

PMID- 21969011
TI  - Association of physical activity with vascular endothelial function and intima
      media thickness.
AB  - BACKGROUND: Impairment of vascular endothelial function and increased intima
      media thickness (IMT) are important early steps in atherogenesis. Longitudinal
      data on the effect of physical activity on endothelial function and IMT in
      healthy adolescents are lacking. We investigated prospectively the association of
      leisure-time physical activity with endothelial function (brachial artery flow
      mediated dilatation; FMD) and aortic IMT in adolescents. METHODS AND RESULTS: FMD
      and IMT were measured with ultrasonography at 13 (n=553), 15 (n=531), and 17
      (n=494) years of age in adolescents participating in a longitudinal
      atherosclerosis prevention study (Special Turku Coronary Risk Factor Intervention
      Project for Children). Mean aortic IMT, maximum FMD, and total FMD response (area
      under the dilatation curve 40 to 180 seconds after hyperemia) were calculated.
      Leisure-time physical activity was assessed with a questionnaire, and metabolic
      equivalent (MET) hours per week of leisure-time physical activity were calculated
      by multiplying weekly mean exercise intensity, duration, and frequency. Leisure
      time physical activity was directly associated with endothelial function (P for
      maximum FMD=0.0021, P for total FMD response=0.0036) and inversely with IMT
      (P=0.011) after adjustment for age, sex, body mass index, high-density
      lipoprotein/total cholesterol, systolic blood pressure, and C-reactive protein
      and regarding FMD brachial artery diameter. Sedentary adolescents who increased
      their leisure-time physical activity from <5 to >5 (IMT) or >30 (maximum FMD) MET
      h/wk between 13 and 17 years of age had an increased maximum FMD (P=0.031) and
      decreased progression of IMT (P=0.047) compared with adolescents who remained
      sedentary. IMT progression was attenuated in persistently active adolescents
      compared with those who became sedentary (P=0.0072). CONCLUSIONS: Physical
      activity is favorably associated with endothelial function and IMT in
      adolescents. Importantly, a moderate increase in physical activity is related to
      decreased progression of IMT. A physically active lifestyle seems to prevent the
      development of subclinical atherosclerotic vascular changes in healthy
      adolescents. Clinical Trial Registration- URL: http://www.clinicaltrials.gov.
      Unique identifier: NCT00223600 (STRIP19902010).

PMID- 21969012
TI  - Transcoronary concentration gradients of circulating microRNAs.
AB  - BACKGROUND: Circulating levels of microRNA (miR) have been proposed as biomarkers
      for cardiovascular disease. To identify the heart as a potential source for miRs
      released into the circulation, we measured concentration gradients across the
      coronary circulation for muscle-enriched (miR-133a, miR-499, miR-208a), vascular
      (miR-126, miR-92a), leukocyte-related (miR-155), and platelet-enriched (miR-223)
      miRs. METHODS AND RESULTS: Circulating miRs were measured by TaqMan polymerase
      chain reaction in EDTA-plasma simultaneously obtained from the aorta and the
      coronary venous sinus in patients without coronary artery disease (n=7), with
      stable coronary artery disease (n=31), and with troponin-positive acute coronary
      syndromes (n=19). Circulating levels of the muscle-enriched miR-499 (>20-fold;
      P<0.01), miR-133a (11-fold; P<0.01), and miR-208a (5-fold; P<0.01) were
      significantly elevated in the aorta of troponin-positive acute coronary syndrome
      patients compared with patients with coronary artery disease. Importantly, there
      was a significant increase in circulating levels of miR-499 and miR-133a across
      the coronary circulation in troponin-positive acute coronary syndrome patients,
      suggestive of a release into the coronary circulation during myocardial injury.
      Indeed, miR-499 concentration gradients were significantly correlated with the
      extent of myocardial damage as measured by high-sensitivity troponin T (r=0.70,
      P<0.01). In contrast, circulating levels of miR-126 (P=0.16) decreased during
      transcoronary passage in patients with evidence of myocardial injury, suggesting
      consumption during transcoronary passage. CONCLUSIONS: Muscle-enriched miR-499
      and miR-133a are released from the heart into the coronary circulation on
      myocardial injury, whereas the vascular miR-126 is consumed during transcoronary
      passage. The differential regulation of circulating miRs during the transcoronary
      passage might provide important insights to exploit their role as cardiac
      biomarkers. Clinical Trial Registration- URL: http://www.germanctr.de. Unique
      identifier: DRKS00000207; in German Clinical Trials Registry.

PMID- 21969013
TI  - Urokinase-type plasminogen activator promotes paracellular transmigration of
      neutrophils via Mac-1, but independently of urokinase-type plasminogen activator
      receptor.
AB  - BACKGROUND: Urokinase-type plasminogen activator (uPA) has recently been
      implicated in the pathogenesis of ischemia-reperfusion (I/R) injury. The
      underlying mechanisms remain largely unclear. METHODS AND RESULTS: Using in vivo
      microscopy on the mouse cremaster muscle, I/R-elicited firm adherence and
      transmigration of neutrophils were found to be significantly diminished in uPA
      deficient mice and in mice treated with the uPA inhibitor WX-340, but not in uPA
      receptor (uPAR)-deficient mice. Interestingly, postischemic leukocyte responses
      were significantly reduced on blockade of the integrin CD11b/Mac-1, which also
      serves as uPAR receptor. Using a cell transfer technique, postischemic adherence
      and transmigration of wild-type leukocytes were significantly decreased in uPA
      deficient animals, whereas uPA-deficient leukocytes exhibited a selectively
      reduced transmigration in wild-type animals. On I/R or stimulation with
      recombinant uPA, >90% of firmly adherent leukocytes colocalized with CD31
      immunoreactive endothelial junctions as detected by in vivo fluorescence
      microscopy. In a model of hepatic I/R, treatment with WX-340 significantly
      attenuated postischemic neutrophil infiltration and tissue injury. CONCLUSIONS:
      Our data suggest that endothelial uPA promotes intravascular adherence, whereas
      leukocyte uPA facilitates the subsequent paracellular transmigration of
      neutrophils during I/R. This process is regulated via CD11b/Mac-1, and does not
      require uPAR. Pharmacological blockade of uPA interferes with these events and
      effectively attenuates postischemic tissue injury.

PMID- 21969014
TI  - Cardiac magnetic resonance imaging pericardial late gadolinium enhancement and
      elevated inflammatory markers can predict the reversibility of constrictive
      pericarditis after antiinflammatory medical therapy: a pilot study.
AB  - BACKGROUND: Constrictive pericarditis (CP) is a disabling disease, and usually
      requires pericardiectomy to relieve heart failure. Reversible CP has been
      described, but there is no known method to predict the reversibility. Pericardial
      inflammation may be a marker for reversibility. As a pilot study, we assessed
      whether cardiac magnetic resonance imaging pericardial late gadolinium
      enhancement (LGE) and inflammatory biomarkers could predict the reversibility of
      CP after antiinflammatory therapy. METHOD AND RESULTS: Twenty-nine CP patients
      received antiinflammatory medications after cardiac magnetic resonance imaging.
      Fourteen patients had resolution of CP, whereas 15 patients had persistent CP
      after 13 months of follow-up. Baseline LGE pericardial thickness was greater in
      the group with reversible CP than in the persistent CP group (4 +/- 1 versus 2 +/
      1 mm, P = 0.001). Qualitative intensity of pericardial LGE was moderate or
      severe in 93% of the group with reversible CP and in 33% of the persistent CP
      group (P = 0.002). Cardiac magnetic resonance imaging LGE pericardial thickness
      >= 3 mm had 86% sensitivity and 80% specificity to predict CP reversibility. The
      group with reversible CP also had higher baseline C-reactive protein and
      erythrocyte sedimentation rate than the persistent CP group (59 +/- 52 versus 12
      +/- 14 mg/L, P = 0.04 and 49 +/- 25 versus 15 +/- 16 mm/h, P = 0.04,
      respectively). Antiinflammatory therapy was associated with a reduction in C
      reactive protein, erythrocyte sedimentation rate, and pericardial LGE in the
      group with reversible CP but not in the persistent CP group. CONCLUSIONS:
      Reversible CP was associated with pericardial and systemic inflammation.
      Antiinflammatory therapy was associated with a reduction in pericardial and
      systemic inflammation and LGE pericardial thickness, with resolution of CP
      physiology and symptoms. Further studies in a larger number of patients are
      needed.

PMID- 21969015
TI  - Maternal and fetal factors associated with mortality and morbidity in a multi
      racial/ethnic registry of anti-SSA/Ro-associated cardiac neonatal lupus.
AB  - BACKGROUND: Cardiac manifestations of neonatal lupus include conduction disease
      and, rarely, an isolated cardiomyopathy. This study was initiated to determine
      the mortality and morbidity of cardiac neonatal lupus and associated risk factors
      in a multi-racial/ethnic US-based registry to provide insights into the
      pathogenesis of antibody-mediated injury and data for counseling. METHODS AND
      RESULTS: Three hundred twenty-five offspring exposed to maternal anti-SSA/Ro
      antibodies with cardiac neonatal lupus met entry criteria. Maternal, fetal
      echocardiographic, and neonatal risk factors were assessed for association with
      mortality. Fifty-seven (17.5%) died, 30% in utero. The probability of in utero
      death was 6%. The cumulative probability of survival at 10 years for a child born
      alive was 86%. Fetal echocardiographic risk factors associated with increased
      mortality in a multivariable analysis of all cases included hydrops and
      endocardial fibroelastosis. Significant predictors of in utero death were hydrops
      and earlier diagnosis, and of postnatal death were hydrops, endocardial
      fibroelastosis, and lower ventricular rate. Isolated heart block was associated
      with a 7.8% case fatality rate, whereas the concomitant presence of dilated
      cardiomyopathy or endocardial fibroelastosis quadrupled the case fatality rate.
      There was a significantly higher case fatality rate in minorities compared with
      whites, who were at a lower risk of hydrops and endocardial fibroelastosis.
      Pacing was required in 70%; cardiac transplantation was required in 4 children.
      CONCLUSION: Nearly one fifth of fetuses who develop cardiac neonatal lupus die of
      complications predicted by echocardiographic abnormalities consistent with
      antibody-associated disease beyond the atrioventricular node. The disparity in
      outcomes observed between minorities and whites warrants further investigation.

PMID- 21969017
TI  - Health-related quality of life after transcatheter aortic valve replacement in
      inoperable patients with severe aortic stenosis.
AB  - Background- Transcatheter aortic valve replacement (TAVR) has been shown to
      improve survival compared with standard therapy in patients with severe aortic
      stenosis who cannot have surgery. The effects of TAVR on health-related quality
      of life have not been reported from a controlled study.  Methods and Results- The
      Placement of Aortic Transcatheter Valves (PARTNER) trial randomized patients with
      symptomatic, severe aortic stenosis who were not candidates for surgical valve
      replacement to TAVR (n=179) or standard therapy (n=179). Health-related quality
      of life was assessed at baseline and at 1, 6, and 12 months with the Kansas City
      Cardiomyopathy Questionnaire (KCCQ) and the 12-item Short Form-12 General Health
      Survey (SF-12). The primary end point was the KCCQ overall summary score (range,
      0-100; higher=better). At baseline, mean KCCQ summary scores (35+/-20) and SF-12
      physical summary scores (28+/-7) were markedly depressed. Although the KCCQ
      summary score improved from baseline in both groups, the extent of improvement
      was greater after TAVR compared with control at 1 month (mean between-group
      difference, 13 points; 95% confidence interval, 8-19; P<0.001) with larger
      benefits at 6 months (mean difference, 21 points; 95% confidence interval, 15-27;
      P<0.001) and 12 months (mean difference, 26 points; 95% confidence interval, 19
      33; P<0.001). At 12 months, TAVR patients also reported higher SF-12 physical and
      mental health scores with mean differences compared with standard care of 5.7 and
      6.4 points, respectively (P<0.001 for both comparisons).  Conclusions- Among
      inoperable patients with severe aortic stenosis, compared with standard care,
      TAVR resulted in significant improvements in health-related quality of life that
      were maintained for at least 1 year.  Clinical Trials Registration- URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00530894.

PMID- 21969016
TI  - Wnt signaling mediates pathological vascular growth in proliferative retinopathy.
AB  - BACKGROUND: Ischemic proliferative retinopathy, characterized by pathological
      retinal neovascularization, is a major cause of blindness in working-age adults
      and children. Defining the molecular pathways distinguishing pathological
      neovascularization from normal vessels is critical to controlling these blinding
      diseases with targeted therapy. Because mutations in Wnt signaling cause
      defective retinal vasculature in humans with some characteristics of the
      pathological vessels in retinopathy, we investigated the potential role of Wnt
      signaling in pathological retinal vascular growth in proliferative retinopathy.
      METHODS AND RESULTS: In this study, we show that Wnt receptors (Frizzled4 and low
      density lipoprotein receptor-related protein5 [Lrp5]) and activity are
      significantly increased in pathological neovascularization in a mouse model of
      oxygen-induced proliferative retinopathy. Loss of Wnt coreceptor Lrp5 and
      downstream signaling molecule dishevelled2 significantly decreases the formation
      of pathological retinal neovascularization in retinopathy. Loss of Lrp5 also
      affects retinal angiogenesis during development and formation of the blood
      retinal barrier, which is linked to significant downregulation of tight junction
      protein claudin5 in Lrp5(-/-) vessels. Blocking claudin5 significantly suppresses
      Wnt pathway-driven endothelial cell sprouting in vitro and developmental and
      pathological vascular growth in retinopathy in vivo. CONCLUSIONS: These results
      demonstrate an important role of Wnt signaling in pathological vascular
      development in retinopathy and show a novel function of Cln5 in promoting
      angiogenesis.

PMID- 21969018
TI  - Chronic thromboembolic pulmonary hypertension (CTEPH): results from an
      international prospective registry.
AB  - BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is often a
      sequel of venous thromboembolism with fatal natural history; however, many cases
      can be cured by pulmonary endarterectomy. The clinical characteristics and
      current management of patients enrolled in an international CTEPH registry was
      investigated. METHODS AND RESULTS: The international registry included 679 newly
      diagnosed (<=6 months) consecutive patients with CTEPH, from February 2007 until
      January 2009. Diagnosis was confirmed by right heart catheterization, ventilation
      perfusion lung scintigraphy, computerized tomography, and/or pulmonary
      angiography. At diagnosis, a median of 14.1 months had passed since first
      symptoms; 427 patients (62.9%) were considered operable, 247 (36.4%) nonoperable,
      and 5 (0.7%) had no operability data; 386 patients (56.8%, ranging from 12.0%-
      60.9% across countries) underwent surgery. Operable patients did not differ from
      nonoperable patients relative to symptoms, New York Heart Association class, and
      hemodynamics. A history of acute pulmonary embolism was reported for 74.8% of
      patients (77.5% operable, 70.0% nonoperable). Associated conditions included
      thrombophilic disorder in 31.9% (37.1% operable, 23.5% nonoperable) and
      splenectomy in 3.4% of patients (1.9% operable, 5.7% nonoperable). At the time of
      CTEPH diagnosis, 37.7% of patients initiated at least 1 pulmonary arterial
      hypertension-targeted therapy (28.3% operable, 53.8% nonoperable). Pulmonary
      endarterectomy was performed with a 4.7% documented mortality rate. CONCLUSIONS:
      Despite similarities in clinical presentation, operable and nonoperable CTEPH
      patients may have distinct associated medical conditions. Operability rates vary
      considerably across countries, and a substantial number of patients (operable and
      nonoperable) receive off-label pulmonary arterial hypertension-targeted
      treatments.

PMID- 21969019
TI  - Correlates of delayed recognition and treatment of acute type A aortic
      dissection: the International Registry of Acute Aortic Dissection (IRAD).
AB  - BACKGROUND: In acute aortic dissection, delays exist between presentation and
      diagnosis and, once diagnosed, definitive treatment. This study aimed to define
      the variables associated with these delays. METHODS AND RESULTS: Acute aortic
      dissection patients enrolled in the International Registry of Acute Aortic
      Dissection (IRAD) between 1996 and January 2007 were evaluated for factors
      contributing to delays in presentation to diagnosis and in diagnosis to surgery.
      Multiple linear regression was performed to determine relative delay time ratios
      (DTRs) for individual correlates. The median time from arrival at the emergency
      department to diagnosis was 4.3 hours (quartile 1-3, 1.5-24 hours; n=894
      patients) and from diagnosis to surgery was 4.3 hours (quartile 1-3, 2.4-24
      hours; n=751). Delays in acute aortic dissection diagnosis occurred in female
      patients; those with atypical symptoms that were not abrupt or did not include
      chest, back, or any pain; patients with an absence of pulse deficit or
      hypotension; or those who initially presented to a nontertiary care hospital (all
      P<0.05). The largest relative DTRs were for fever (DTR=5.11; P<0.001) and
      transfer from nontertiary hospital (DTR=3.34; P<0.001). Delay in time from
      diagnosis to surgery was associated with a history of previous cardiac surgery,
      presentation without abrupt or any pain, and initial presentation to a
      nontertiary care hospital (all P<0.001). The strongest factors associated with
      operative delay were prolonged time from presentation to diagnosis (DTR=1.35;
      P<0.001), race other than white (DTR=2.25; P<0.001), and history of coronary
      artery bypass surgery (DTR=2.81; P<0.001). CONCLUSIONS: Improved physician
      awareness of atypical presentations and prompt transport of acute aortic
      dissection patients could reduce crucial time variables.

PMID- 21969021
TI  - Bilateral dorsal cochlear nucleus lesions prevent acoustic-trauma induced
      tinnitus in an animal model.
AB  - Animal experiments suggest that chronic tinnitus ("ringing in the ears") may
      result from processes that overcompensate for lost afferent input. Abnormally
      elevated spontaneous neural activity has been found in the dorsal cochlear
      nucleus (DCN) of animals with psychophysical evidence of tinnitus. However, it
      has also been reported that DCN ablation fails to reduce established tinnitus.
      Since other auditory areas have been implicated in tinnitus, the role of the DCN
      is unresolved. The apparently conflicting electrophysiological and lesion data
      can be reconciled if the DCN serves as a necessary trigger zone rather than a
      chronic generator of tinnitus. The present experiment used lesion procedures
      identical to those that failed to decrease pre-existing tinnitus. The exception
      was that lesions were done prior to tinnitus induction. Young adult rats were
      trained and tested using a psychophysical procedure shown to detect tinnitus.
      Tinnitus was induced by a single unilateral high-level noise exposure. Consistent
      with the trigger hypothesis, bilateral dorsal DCN lesions made before high-level
      noise exposure prevented the development of tinnitus. A protective effect
      stemming from disruption of the afferent pathway could not explain the outcome
      because unilateral lesions ipsilateral to the noise exposure did not prevent
      tinnitus and unilateral lesions contralateral to the noise exposure actually
      exacerbated the tinnitus. The DCN trigger mechanism may involve plastic circuits
      that, through loss of inhibition, or upregulation of excitation, increase
      spontaneous neural output to rostral areas such as the inferior colliculus. The
      increased drive could produce persistent pathological changes in the rostral
      areas, such as high-frequency bursting and decreased interspike variance, that
      comprise the chronic tinnitus signal.

PMID- 21969022
TI  - Unanesthetized auditory cortex exhibits multiple codes for gaps in cochlear
      implant pulse trains.
AB  - Cochlear implant listeners receive auditory stimulation through amplitude
      modulated electric pulse trains. Auditory nerve studies in animals demonstrate
      qualitatively different patterns of firing elicited by low versus high pulse
      rates, suggesting that stimulus pulse rate might influence the transmission of
      temporal information through the auditory pathway. We tested in awake guinea pigs
      the temporal acuity of auditory cortical neurons for gaps in cochlear implant
      pulse trains. Consistent with results using anesthetized conditions, temporal
      acuity improved with increasing pulse rates. Unlike the anesthetized condition,
      however, cortical neurons responded in the awake state to multiple distinct
      features of the gap-containing pulse trains, with the dominant features varying
      with stimulus pulse rate. Responses to the onset of the trailing pulse train
      (Trail-ON) provided the most sensitive gap detection at 1,017 and 4,069 pulse-per
      second (pps) rates, particularly for short (25 ms) leading pulse trains. In
      contrast, under conditions of 254 pps rate and long (200 ms) leading pulse
      trains, a sizeable fraction of units demonstrated greater temporal acuity in the
      form of robust responses to the offsets of the leading pulse train (Lead-OFF).
      Finally, TONIC responses exhibited decrements in firing rate during gaps, but
      were rarely the most sensitive feature. Unlike results from anesthetized
      conditions, temporal acuity of the most sensitive units was nearly as sharp for
      brief as for long leading bursts. The differences in stimulus coding across pulse
      rates likely originate from pulse rate-dependent variations in adaptation in the
      auditory nerve. Two marked differences from responses to acoustic stimulation
      were: first, Trail-ON responses to 4,069 pps trains encoded substantially shorter
      gaps than have been observed with acoustic stimuli; and second, the Lead-OFF gap
      coding seen for <15 ms gaps in 254 pps stimuli is not seen in responses to
      sounds. The current results may help to explain why moderate pulse rates around
      1,000 pps are favored by many cochlear implant listeners.

PMID- 21969023
TI  - Proteasomal degradation of ubiquitinated proteins in oocyte meiosis and
      fertilization in mammals.
AB  - Gametogenesis and fertilization are the key events in sexual reproduction. In the
      female, meiosis results in a large oocyte that is competent for fertilization and
      fundamental for the success of early embryonic development. Progression through
      meiosis is monitored by fine regulatory mechanisms. In this review, we focus on
      one of the most well-known regulatory elements, the E3 ligase APC/C, which
      mediates proteolytic degradation of a number of important substrates via the
      ubiquitin proteasome pathway (UPP). The UPP also indirectly regulates protein
      synthesis by affecting proteins involved in RNA metabolism, a process that is
      paramount for the transcriptionally silent oocyte. During the past few years,
      more evidence has accumulated to suggest that the UPP has an important role in
      zona pellucida penetration and gamete fusion in mammals. This review focuses on
      the function of the UPP in regulating oocyte meiotic maturation in mammals, with
      special attention to its role in chromosome segregation and polar body extrusion,
      its role in the acquisition of meiotic/developmental competence and recent
      advances in our understanding of the UPP role in fertilization.

PMID- 21969024
TI  - The effects of combinatorial treatments with stress inducing molecules on growth
      of E. coli colonies.
AB  - Stress inducing molecules affect both the mean behavior of bacterial growth and
      also variations in the growth. While the mechanisms that cause changes in the
      mean behavior are well understood, little is known about changes in the variation
      of the population. A true understanding of how organisms respond to stress must
      include an understanding of the mechanisms and purposes of changes in variation
      and the distribution not directly related to changes in the mean of the
      population. We have explored the results of combinatorial treatments using EDTA,
      copper sulfate, hydrogen peroxide, and hydrochloric acid as stress inducing
      molecules on bacterial colony formation and area on LB-agar plates. Three
      different combinations of X-gal and IPTG were used to create different background
      conditions. Some treatments alter the variation and/or the distribution of the
      area without having a significant effect on the mean, others affect the mean
      without altering the distribution, and yet others affect distribution and the
      mean.

PMID- 21969025
TI  - Genomic library screening for viruses from the human dental plaque revealed
      pathogen-specific lytic phage sequences.
AB  - Bacterial pathogenesis presents an astounding arsenal of virulence factors that
      allow them to conquer many different niches throughout the course of infection.
      Principally fascinating is the fact that some bacterial species are able to
      induce different diseases by expression of different combinations of virulence
      factors. Nevertheless, studies aiming at screening for the presence of
      bacteriophages in humans have been limited. Such screening procedures would
      eventually lead to identification of phage-encoded properties that impart
      increased bacterial fitness and/or virulence in a particular niche, and hence,
      would potentially be used to reverse the course of bacterial infections. As the
      human oral cavity represents a rich and dynamic ecosystem for several upper
      respiratory tract pathogens. However, little is known about virus diversity in
      human dental plaque which is an important reservoir. We applied the culture
      independent approach to characterize virus diversity in human dental plaque
      making a library from a virus DNA fraction amplified using a multiple
      displacement method and sequenced 80 clones. The resulting sequence showed 44%
      significant identities to GenBank databases by TBLASTX analysis. TBLAST homology
      comparisons showed that 66% was viral; 18% eukarya; 10% bacterial; 6% mobile
      elements. These sequences were sorted into 6 contigs and 45 single sequences in
      which 4 contigs and a single sequence showed significant identity to a small
      region of a putative prophage in the Corynebacterium diphtheria genome. These
      findings interestingly highlight the uniqueness of over half of the sequences,
      whilst the dominance of a pathogen-specific prophage sequences imply their role
      in virulence.

PMID- 21969026
TI  - [Breast feeding during methadon- and buprenorphin therapy].
AB  - The number of opiate addicted patients treated with opioid replacement therapy is
      continuously increasing. In Germany, 57.7% of these patients are treated with
      methadone and 18.6% with buprenorphine. This maintenance therapy provides several
      advantages while addicted pregnant women and their foetus have a high benefit
      from appropriate replacement therapy. However, the recommendations concerning
      breast feeding during an opioid replacement therapy are discussed
      controversially, because methadone as well as buprenorphine accumulate in breast
      milk. This accumulation might cause damages to the newborn's health; so, child
      benefits of breast feeding have to be balanced with possible health risks.This
      review provides an overview of a selective literature search based on the PubMed
      database and german consensus recommendations. Used search terms included:
      (methadone*) AND (breastfeeding OR lactation), (methadone*) AND (human milk),
      (buprenorphine*) AND (breastfeeding OR lactation) and (buprenorphine*) AND (human
      milk).According to the available literature, addicted women, substinated with
      methadone or buprenorphine are allowed to breast feed their newborns. The
      advantages of breast feeding prevail the risks of an infant opiate intoxication
      caused by methadone or buprenorphine.

PMID- 21969027
TI  - Lethal junctional epidermolysis bullosa with pyloric atresia due to compound
      heterozygosity for two novel mutations in the integrin beta4 gene.
AB  - BACKGROUND: Junctional epidermolysis bullosa with pyloric atresia (JEB-PA) is a
      rare autosomal recessive disease with blister formation within the lamina lucida
      due to mutations in the integrin beta4 (ITGB4) and alpha6 (ITGA6) genes. CASE
      REPORT: A female preterm infant, first child of healthy non-consanguineous
      parents, was born at 26 + 4 weeks of gestation by caesarean section, following
      polyhydramnion and abruption of placenta. She presented with extensive areas of
      denuded skin on both lateral sides of the head, neck and extremities. Auricles
      were hypoplastic. Abdominal ultrasound and X-ray were suggestive of pyloric
      atresia which was revised surgically on the 4th day of life. Further course was
      complicated by progressive skin detachment, sepsis, and renal insufficiency with
      fatal outcome at 18 days of age. Immunofluorescence mapping of cryopreserved skin
      showed junctional cleft formation with negative staining for integrin alpha6 and
      integrin beta4. Mutational analysis disclosed compound heterozygosity for two
      novel nonsense mutations in the ITGB4 gene: c.600dupC/p.F201fsX14 and
      c.2533C>T/p.Q845X. 2 subsequent pregnancies were terminated following prenatal
      diagnosis disclosing the same ITGB4 mutations, a 4th pregnancy was unaffected.
      CONCLUSION: We describe a case of lethal JEB-PA with negative immunoreactivity to
      integrin alpha6 and integrin beta4 predicting a poor outcome. Identification of
      compound heterozygosity for two novel ITGB4 mutations in the affected preterm
      infant permitted prenatal diagnosis and finally birth of a healthy sibling.

PMID- 21969028
TI  - Peer victimization and parental psychological control in adolescence.
AB  - With a sample of 831 U.S. adolescents (49% girls) followed from 9th to 11th
      grade, the directionality of the association between school-based peer
      victimization and adolescents' perception of their parents' psychological control
      were examined. Possible mediating influences of internalizing symptoms were also
      explored. The results highlight the relevance of adolescent-to-parent influences
      during adolescence by demonstrating that physical peer victimization was
      predictive of increases in mother's psychological control but parental
      psychological control did not predict subsequent peer victimization. These direct
      effects were present above and beyond the contribution of adolescent
      internalizing symptoms to higher parental psychological control. Practical
      implications of the primacy of adolescent-to-parent influences in predicting the
      social adjustment of victims of peer harassment are discussed.

PMID- 21969029
TI  - Detection of histone modifications in plant leaves.
AB  - Chromatin structure is important for the regulation of gene expression in
      eukaryotes. In this process, chromatin remodeling, DNA methylation, and covalent
      modifications on the amino-terminal tails of histones H3 and H4 play essential
      roles(1-2). H3 and H4 histone modifications include methylation of lysine and
      arginine, acetylation of lysine, and phosphorylation of serine residues(1-2).
      These modifications are associated either with gene activation, repression, or a
      primed state of gene that supports more rapid and robust activation of expression
      after perception of appropriate signals (microbe-associated molecular patterns,
      light, hormones, etc.)(3-7).  Here, we present a method for the reliable and
      sensitive detection of specific chromatin modifications on selected plant genes.
      The technique is based on the crosslinking of (modified) histones and DNA with
      formaldehyde(8,9), extraction and sonication of chromatin, chromatin
      immunoprecipitation (ChIP) with modification-specific antibodies(9,10), de
      crosslinking of histone-DNA complexes, and gene-specific real-time quantitative
      PCR. The approach has proven useful for detecting specific histone modifications
      associated with C(4;) photosynthesis in maize(5,11) and systemic immunity in
      Arabidopsis(3).

PMID- 21969031
TI  - A Ball of Cotton Wool Masquerading as a Conjunctiva Mass.

PMID- 21969030
TI  - Characterization of red wines from South America based on sensory properties and
      antioxidant activity.
AB  - BACKGROUND: It is widely accepted that red wines constitute one of the most
      important sources of dietary polyphenolic antioxidants. However, it is still not
      known how some variables such as variety, vintage, country of origin, and retail
      price are associated with the antioxidant activity and sensory profile of South
      American red wines. In this regard, 80 samples produced in Brazil, Chile and
      Argentina were assessed in relation to their sensory properties, color and in
      vitro antioxidant activity, and results were subjected to multivariate
      statistical techniques. RESULTS: Samples were grouped in clusters, characterized
      by high, intermediate and low in vitro antioxidant activity, sensory properties
      and prices. It was possible to observe that wines with high antioxidant activity
      were associated to high retail prices and overall perception of sensory quality.
      CONCLUSION: South American wines produced from Vitis vinifera such as Syrah,
      Malbec and Cabernet Sauvignon had higher in vitro antioxidant activity and also
      higher sensory quality than wines produced from Vitis labrusca. This result was
      independent of vintage (2002-2010), corroborating the idea that the same grape
      varietal, even when produced in different years, displays similar sensory
      characteristics and antioxidant activity.

PMID- 21969032
TI  - Expression of multiple tfb genes in different Halobacterium salinarum strains and
      interaction of TFB with transcriptional activator GvpE.
AB  - Halobacterium salinarum NRC-1 contains multiple TBP and TFB proteins required for
      the recruitment of RNA polymerase for transcription initiation. The presence and
      the expression of genes encoding TFB were investigated in the two Hbt. salinarum
      strains NRC-1 and PHH1 and the mutant strain PHH4. The plasmid-encoded tfbC and
      tfbE genes of NRC-1 were lacking in PHH1 and PHH4. The 5'-end of the tfbF
      transcript was determined and contained a 5'-untranslated region of 39
      nucleotides able to form a stem-loop structure. The expression of these tfb genes
      was studied in cultures growing at 15, 37 degrees C and under heat shock
      conditions. Cold temperatures reduced growth and except for tfbF also the amounts
      of all tfb transcripts. However, the formation of gas vesicles increased in PHH1
      and NRC-1. Heat shock reduced growth of PHH1 and NRC-1, but PHH4 was not
      affected. A 100-fold increase in tfbA and tfbB mRNA was observed in PHH1 and
      PHH4, whereas NRC-1 reduced the amounts of these transcripts and increased the
      expression of tfbG. All TFB proteins tested were able to interact with the
      transcription activator GvpE involved in gas vesicle formation that thus is able
      to recruit TFB to the gvp promoter.

PMID- 21969034
TI  - Characterization of ligand type of estrogen receptor by MD simulation and mm-PBSA
      free energy analysis.
AB  - Estrogen receptor is a transcription regulator and can bind structurally distinct
      ligands with full agonistic, SERMs, or full antagonistic properties. Crystal
      structures of the ER ligand binding domain (LBD)-complexed with full agonists or
      SERMs show that these ligands induce two different orientations of Helix12 in LBD
      and generate two different conformations, agonist conformation (A conformation)
      and AF2 antagonist conformation (B conformation). To understand how ER ligands
      interact with LBD structurally and energetically, we docked 3 full agonists, 9
      SERMs and 2 full antagonists in both the A and B conformation of ERalpha LBD and
      performed a 4-step molecular dynamics (MD) simulation on all 28 complexes
      followed by mm-PBSA binding free energy calculation. We found that all full
      agonists prefer the A conformation while all SERMs prefer the B conformation.
      Analysis of the mm-PBSA energies revealed that calculated total binding free
      energies (delta PBTOT) and the difference of VDW between complex and the sum of
      receptor of ligands and ligand (delta VDW) have the order of full
      agonists>SERMs>full antagonists. However, the PB surface term has the order of
      full antagonists>SERMs>full agonists. We also found that the sum of the RMSD of
      mainchain atoms of Helix12 and all atoms of ligands in the A conformation is
      significantly lower for full agonists than that of the other ligands. Together,
      we conclude that the three types of ER ligands interact with the A and B
      conformations of ERalpha LBD differently and same type of ligands interact
      similarly. These findings will be useful in understanding the mechanism of ER
      antagonism and can be used in ligand type prediction.

PMID- 21969035
TI  - Parental perspectives on leg length discrepancy.
AB  - This study investigated perspectives of 58 parents on leg length discrepancy
      (LLD) of their children using a questionnaire survey. There were significant
      differences in the pain/comfort (P=0.021) and global function subscales (P=0.013)
      of the pediatric outcomes data collection instrument between the idiopathic LLD
      and posttraumatic LLD groups. Significant differences in the items with regard to
      the satisfaction with appearance (P=0.012), preference for surgical treatment
      (P<0.001), effect on happiness (P=0.004), and concerns over possible operations
      (P=0.010) were observed between the LLD of 2 cm or more and LLD of less than 2 cm
      groups. Logistic regression showed that the only significant contributing factor
      to a willingness to seek treatment was the amount of LLD (P=0.004).

PMID- 21969036
TI  - Genomics: Getting personal and regional.

PMID- 21969033
TI  - NF-kappaB and cancer: a paradigm of Yin-Yang.
AB  - Recent studies have clearly linked nuclear factor-kappaB (NF-kappaB), a
      transcription factor that plays a central role in regulating immune and
      inflammatory responses, to tumor development, progression, and metastasis as well
      as tumor therapy resistance. However, it still remains largely unknown on how the
      tightly regulated NF-kappaB becomes constitutively activated in tumorigenesis and
      how the original cancer immunosurveillance function of NF-kappaB is transformed
      to be tumorigenic. To address these important issues for cancer prevention and
      treatment, we discuss current understanding of the molecular mechanisms and
      molecules involved in the oncogenic activation of NF-kappaB. We also discuss
      current understanding of how NF-kappaB coordinates the inflammatory and malignant
      cells in tumorigenesis.

PMID- 21969037
TI  - The early bird catches the worm: new technologies for the Caenorhabditis elegans
      toolkit.
AB  - The inherent simplicity of Caenorhabditis elegans and its extensive genetic
      toolkit make it ideal for studying complex biological processes. Recent
      developments further increase the usefulness of the worm, including new methods
      for: altering gene expression, altering physiology using optogenetics,
      manipulating large numbers of worms, automating laborious processes and
      processing high-resolution images. These developments both enhance the worm as a
      model for studying processes such as development and ageing and make it an
      attractive model in areas such as neurobiology and behaviour.

PMID- 21969038
TI  - Variation in the mutation rate across mammalian genomes.
AB  - It has been known for many years that the mutation rate varies across the genome.
      However, only with the advent of large genomic data sets is the full extent of
      this variation becoming apparent. The mutation rate varies over many different
      scales, from adjacent sites to whole chromosomes, with the strongest variation
      seen at the smallest scales. Some of these patterns have clear mechanistic bases,
      but much of the rate variation remains unexplained, and some of it is deeply
      perplexing. Variation in the mutation rate has important implications in
      evolutionary biology and underexplored implications for our understanding of
      hereditary disease and cancer.

PMID- 21969039
TI  - Synthesis and oxidation of 2-hydroxynevirapine, a metabolite of the HIV reverse
      transcriptase inhibitor nevirapine.
AB  - Nevirapine (11-cyclopropyl-5,11-dihydro-4-methyl-6H-dipyrido[3,2-b:2',3'
      e][1,4]diazepin-6-one, NVP) is a non-nucleoside HIV-1 reverse transcriptase
      inhibitor used to prevent mother-to-child transmission of the virus. However,
      severe hepatotoxicity and serious adverse cutaneous effects have raised concerns
      about the safety of NVP administration. NVP metabolism yields several phenol-type
      derivatives conceivably capable of undergoing further metabolic oxidation to
      electrophilic quinoid species that could react with bionucleophiles. The covalent
      adducts thus formed might be at the genesis of toxic responses. As an initial
      step to test this hypothesis, we synthesized the phenolic metabolite, 2-hydroxy
      NVP, and investigated its oxidation in vitro. Using potassium nitrosodisulfonate
      and sodium periodate as model oxidants, we obtained evidence for fast generation
      of an electrophilic quinone-imine, which readily underwent hydrolytic conversion
      to fully characterized spiro derivatives, 1'-cyclopropyl-4-methyl-1H,1'H
      spiro[pyridine-2,2'-pyrido[2,3-d]pyrimidine]-3,4',6(3'H)-trione in aqueous media
      and 1'-cyclopropyl-4-methyl-1'H,2H-spiro[pyridine-3,2'-pyrido[2,3-d]pyrimidine]
      2,4',6(1H,3'H)-trione in non-aqueous media. The spiro compound generated in
      aqueous solution underwent subsequent hydrolytic degradation of the NVP ring
      system, whereas the one formed in non-aqueous media was stable to hydrolysis. The
      product profile observed with the chemical oxidants in aqueous solution was
      replicated using lactoperoxidase-mediated oxidation of 2-hydroxy-NVP. These
      observations suggest that metabolic activation of NVP, via Phase I oxidation to 2
      hydroxy-NVP and subsequent generation of a quinone-imine, could occur in vivo and
      play a role in NVP-induced toxicity.

PMID- 21969040
TI  - Neighborhood disorder and incarceration history among urban substance users.
AB  - This research examines the relationship between neighborhood physical and social
      disorder and incarceration history among urban drug users. A cohort of 358
      African American and White urban drug users completed a clinical interview and
      psychological assessment that emphasized cognitive and social-behavioral HIV risk
      factors. The Neighborhood Inventory for Environmental Typology was used to assess
      indicators of physical and social disorder. After controlling for age, gender,
      education, and having a place to live, multivariable analyses revealed that
      living in a neighborhood with moderate or high levels of disorder (odds ratio
      [OR] = 1.63; 95% confidence interval [CI] = [1.02, 2.59]) and drinking alcohol
      every day or nearly every day for 3 months or more (OR = 2.03; 95% CI [1.24,
      3.31]) were associated with incarceration history. Findings suggest that select
      characteristics of disadvantaged communities may be important determinants of
      incarceration vulnerability among urban substance users. Residential improvements
      hold promise to enhance interventions aimed to reduce incarceration.

PMID- 21969041
TI  - Hard outcomes: clinical trials to reduce suicide.

PMID- 21969042
TI  - Anxiety disorders and antipsychotic drugs: a pressing need for more research.

PMID- 21969043
TI  - A new (old) treatment option for depression in Parkinson's disease.

PMID- 21969044
TI  - Digging more deeply for genetic effects in psychiatric illness.

PMID- 21969045
TI  - My Father's Shoes.

PMID- 21969046
TI  - A 200th anniversary of academic psychiatry.

PMID- 21969047
TI  - T3 augmentation in major depressive disorder: safety considerations.

PMID- 21969048
TI  - How dosing might influence the conclusion in an antipsychotic polypharmacy
      effectiveness trial.

PMID- 21969049
TI  - Preventing pain medication dependence.

PMID- 21969050
TI  - Psychosis associated with synthetic cannabinoid agonists: a case series.

PMID- 21969051
TI  - Clozapine rechallenge after excluding the high-risk clozapine-induced
      agranulocytosis genotype of HLA-DQB1 6672G>C.

PMID- 21969052
TI  - Eating disorder as a psychiatric onset of juvenile Huntington's disease.

PMID- 21969053
TI  - Three-dimensional observation of the mouse embryo by micro-computed tomography:
      Meckel's cartilage, otocyst, and/or muscle of tongue.
AB  - Three-dimensional observation during embryogenesis is possible with micro
      computed tomography, but there are no observations of organ size. In this paper,
      three examples of three-dimensional observation of organs by micro-CT are tried.
      At 13.0 days post-coitum, mouse embryos were fixed in 4% paraformaldehyde for 24
      h and stained enbloc by osmium tetroxide overnight. The embryos were then
      embedded in paraffin using standard methods for 24 h. Specimens were analyzed by
      micro-computed tomography and image processing was performed. The entire Meckel's
      cartilage and its relation in the mandible, as well as the complex structure of
      the otocyst, are easily visualized. Although it is difficult to extract detailed
      structures of the tongue muscles, it is possible to identify the inner and
      external tongue muscles. Relation among the organs and other are easily
      visualized. Three-dimensional observation by micro-computed tomography is an
      important technology for visualization of embryogenesis and could be used in
      organ culture.

PMID- 21969054
TI  - RAB8 enhances TMEM205-mediated cisplatin resistance.
AB  - PURPOSE: To determine whether the small endosomal recycling GTPase, RAB8, plays a
      role in TMEM205-associated resistance to the chemotherapeutic drug cisplatin.
      METHODS: Antibodies were used as markers for both genes; confocal microscopy was
      used to visualize their localization in cisplatin-resistant cells. Both single
      and dual-transfections were performed. RESULTS: Expression of RAB8 was markedly
      elevated in human cisplatin-resistant cells. We found that TMEM205 was co
      localized with RAB8. Dual transfectants with over-expression of both TMEM205 and
      RAB8 were found to be up to 4-fold more resistant to cisplatin, while cells
      transfected with RAB8 alone were ~2-fold more resistant. CONCLUSIONS: The
      development of cisplatin resistance appears to be a consequence of pleotropic
      epigenetic alterations. We unravel the role of one gene, the GTPase RAB8, in this
      process. Because its highest expression was at an early step of cisplatin
      resistance, it may be involved in early development of resistance. Increased
      expression of TMEM205 and RAB8 in double-transfected cells and their increased
      resistance to cisplatin indicate an additive effect of these two genes, mediating
      cisplatin resistance. These two proteins are potential biomarkers or targets for
      gene or chemotherapy.

PMID- 21969055
TI  - Poorly differentiated thyroid carcinoma. Are we there yet?
AB  - The article reviews the controversial area of poorly differentiated thyroid
      carcinoma. Consensus criteria that define poorly differentiated thyroid carcinoma
      have been published in 2007. According to these, poorly differentiated thyroid
      carcinoma is a distinct histotype and the term "poorly differentiated" should not
      be used as a synonym for high-grade thyroid cancer. Data in the literature show
      that tumor necrosis and high mitotic activity, but not growth pattern or
      histologic subtype, are prognostic markers for thyroid tumors. This underscores
      the importance of grading to identify thyroid carcinomas that behave
      aggressively. The issue of grading versus typing thyroid tumors is discussed.

PMID- 21969056
TI  - Chronic pain in the elderly with advanced dementia. Are we doing our best for
      their suffering?
AB  - Elderly subjects with advanced dementia are exposed, like all aging individuals,
      to a wide range of chronic degenerative and progressive medical conditions which
      can cause pain and discomfort, both physical and psychological. Pain is defined
      as an unpleasant subjective experience, generally assessed with verbal self
      reporting methods. The inability to report pain verbally - a common occurrence in
      advanced stages of dementia - is widely recognized as the main confounding factor
      in identifying these patients' pain. As several previous studies on pain
      assessment in cognitively impaired elderly subjects systematically eliminated non
      communicative demented patients, it is hard to estimate the prevalence of their
      pain. The lack of pain assessment methods which do not rely on self-reporting
      contributes to under-estimation of the prevalence of pain, particularly among
      institutionalized patients, the majority of whom suffer from some degree of
      dementia. Assessing chronic pain in these frail elderly patients requires careful
      monitoring of any changes in their behavior which may be due to a new source of
      discomfort, rather than an aggravation of their cognitive impairment. Although
      some currently available tools for pain assessment in non-verbal older adults
      seem promising, no single tool has yet been sufficiently validated as reliable
      for widespread adoption in clinical practice. Prior research has documented a
      significantly lower prescription of analgesic medications in demented patients
      than in cognitively intact peers: as untreated or under-treated pain can have
      adverse physical and psychological consequences, there is an urgent need for
      appropriate pain assessment methods in elderly patients with advanced dementia,
      since too many of them continue to suffer needlessly. The purpose of this review
      is to discuss the main tools developed in the last decade for pain assessment in
      non-communicative older individuals, highlighting the strengths and weaknesses of
      each, and providing a guide for their use in clinical practice, particularly in
      geriatric settings.

PMID- 21969057
TI  - Acute fulminant hepatitis with bone marrow failure in an adult due to parvovirus
      B19 infection.

PMID- 21969058
TI  - Enhancement of xylitol production in Candida tropicalis by co-expression of two
      genes involved in pentose phosphate pathway.
AB  - The yeast Candida tropicalis produces xylitol, a natural, low-calorie sweetener
      whose metabolism does not require insulin, by catalytic activity of NADPH
      dependent xylose reductase. The oxidative pentose phosphate pathway (PPP) is a
      major basis for NADPH biosynthesis in C. tropicalis. In order to increase xylitol
      production rate, xylitol dehydrogenase gene (XYL2)disrupted C. tropicalis strain
      BSXDH-3 was engineered to co-express zwf and gnd genes which, respectively
      encodes glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate
      dehydrogenase (6-PGDH), under the control of glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) promoter. NADPH-dependent xylitol production was higher in
      the engineered strain, termed "PP", than in BSXDH-3. In fermentation experiments
      using glycerol as a co-substrate with xylose, strain PP showed volumetric xylitol
      productivity of 1.25 g l(-1) h(-1), 21% higher than the rate (1.04 g l(-1) h(-1))
      in BSXDH-3. This is the first report of increased metabolic flux toward PPP in C.
      tropicalis for NADPH regeneration and enhanced xylitol production.

PMID- 21969059
TI  - Therapeutic drug monitoring in psychiatry.

PMID- 21969060
TI  - AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Psychiatry: Update
      2011.
AB  - Therapeutic drug monitoring (TDM), i. e., the quantification of serum or plasma
      concentrations of medications for dose optimization, has proven a valuable tool
      for the patient-matched psychopharmacotherapy. Uncertain drug adherence,
      suboptimal tolerability, non-response at therapeutic doses, or pharmacokinetic
      drug-drug interactions are typical situations when measurement of medication
      concentrations is helpful. Patient populations that may predominantly benefit
      from TDM in psychiatry are children, pregnant women, elderly patients,
      individuals with intelligence disabilities, forensic patients, patients with
      known or suspected genetically determined pharmacokinetic abnormalities or
      individuals with pharmacokinetically relevant comorbidities. However, the
      potential benefits of TDM for optimization of pharmacotherapy can only be
      obtained if the method is adequately integrated into the clinical treatment
      process. To promote an appropriate use of TDM, the TDM expert group of the
      Arbeitsgemeinschaft fur Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP)
      issued guidelines for TDM in psychiatry in 2004. Since then, knowledge has
      advanced significantly, and new psychopharmacologic agents have been introduced
      that are also candidates for TDM. Therefore the TDM consensus guidelines were
      updated and extended to 128 neuropsychiatric drugs. 4 levels of recommendation
      for using TDM were defined ranging from "strongly recommended" to "potentially
      useful". Evidence-based "therapeutic reference ranges" and "dose related
      reference ranges" were elaborated after an extensive literature search and a
      structured internal review process. A "laboratory alert level" was introduced, i.
      e., a plasma level at or above which the laboratory should immediately inform the
      treating physician. Supportive information such as cytochrome P450 substrate- and
      inhibitor properties of medications, normal ranges of ratios of concentrations of
      drug metabolite to parent drug and recommendations for the interpretative
      services are given. Recommendations when to combine TDM with pharmacogenetic
      tests are also provided. Following the guidelines will help to improve the
      outcomes of psychopharmacotherapy of many patients especially in case of
      pharmacokinetic problems. Thereby, one should never forget that TDM is an
      interdisciplinary task that sometimes requires the respectful discussion of
      apparently discrepant data so that, ultimately, the patient can profit from such
      a joint effort.

PMID- 21969061
TI  - Concurrence of malignant fibrohistiocytoma and Takayasu arteritis: a case report.
AB  - Takayasu arteritis (TA) is a type of systemic large-vessel vasculitis that
      usually affects the aorta and its major branches. It remains unrecognized owing
      to delayed diagnosis (Boltin et al. in Rheumatol Int 27(10):985-987, 2007) and
      non-characteristic clinical features. It has been described in association with
      many autoimmune diseases, such as inflammatory digestive tract diseases. However,
      report of TA associated with tumors, especially malignant tumors, are rare. We
      here presented a case diagnosed by both Takayasu arteritis and malignant fibrous
      histiocytoma, from which we learned not only clinical lessons, but also consensus
      of relationships between these two diseases.

PMID- 21969062
TI  - Effects of bud load on quality of Beogradska besemena and Thompson seedless table
      grapes and cultivar differentiation based on chemometrics of analytical indices.
AB  - BACKGROUND: The effects of bud load on the quality of Beogradska besemena and
      Thompson seedless table grape cultivars were studied. Two pruning treatments were
      imposed: 44 and 18 buds per vine for Beogradska besemena and 44 and 22 buds per
      vine for Thompson seedless. RESULTS: In Beogradska besemena the reduction of bud
      load decreased titratable acidity (-4%), skin dry weight (-16%) and malic and
      citric acid contents (-43 and - 20%) and increased tartaric acid content (14%).
      The decrease in pulp antioxidant activity (-36%) was related to the decrease in
      hydroxycinnamoyl tartaric acid content (-13%). Concerning skin, the reduction of
      bud load decreased catechin and caffeoyl tartaric acid contents (-42 and - 40%)
      and significantly increased rutin and quercetin-3-O-glucopyranoside contents as
      specific compounds and flavonoids and proanthocyanidins (9 and 21%) as classes of
      compounds, thus causing an increase in antioxidant activity (6%). In Thompson
      seedless the reduction of bud load increased soluble solid content (7%), acidity
      (9%) and concentrations of the three organic acids (7, 3 and 14%). The increase
      in pulp antioxidant activity (25%) could be attributed to the increase in total
      phenolics (69%). The reduction of bud load caused a significant decrease in
      quercetin-3-O-glucopyranoside (-26%) and antioxidant activity (-15%) in skin.
      Principal component analysis allowed good separation between samples of the two
      cultivars, independently of bud level. CONCLUSION: The results indicate that the
      effects of different bud loads are cultivar-dependent. Bud load and genotype
      differences were shown to dramatically impact the quality and antioxidant
      properties of table grape.

PMID- 21969063
TI  - Mesenteric artery contraction and relaxation studies using automated wire
      myography.
AB  - Proximal resistance vessels, such as the mesenteric arteries, contribute
      substantially to the peripheral resistance. These small vessels of between 100
      400 MUm in diameter function primarily in directing blood flow to various organs
      according to the overall requirements of the body. The rat mesenteric artery has
      a diameter greater than 100 MUm. The myography technique, first described by
      Mulvay and Halpern(1), was based on the method proposed by Bevan and Osher(2).
      The technique provides information about small vessels under isometric
      conditions, where substantial shortening of the muscle preparation is prevented.
      Since force production and sensitivity of vessels to different agonists is
      dependent on the extent of stretch, according to active tension-length relation,
      it is essential to conduct contraction studies under isometric conditions to
      prevent compliance of the mounting wires. Stainless steel wires are preferred to
      tungsten wires because of oxidation of the latter, which affects recorded
      responses(3).The technique allows for the comparison of agonist-induced
      contractions of mounted vessels to obtain evidence for normal function of
      vascular smooth muscle cell receptors. We have shown in several studies that
      isolated mesenteric arteries that are contracted with phenylyephrine relax upon
      addition of cumulative concentrations of extracellular calcium (Ca(2+)(e;)). The
      findings led us to conclude that perivascular sensory nerves, which express the G
      protein-coupled Ca(2+)-sensing receptor (CaR), mediate this vasorelaxation
      response. Using an automated wire myography method, we show here that mesenteric
      arteries from Wistar, Dahl salt-sensitive(DS) and Dahl salt-resistant (DR) rats
      respond differently to Ca(2+)(e;). Tissues from Wistar rats showed higher Ca(2+)
      sensitivity compared to those from DR and DS. Reduced CaR expression in
      mesenteric arteries from DS rats correlates with reduced Ca(2+)(e;)-induced
      relaxation of isolated, pre-contracted arteries. The data suggest that the CaR is
      required for relaxation of mesenteric arteries under increased adrenergic tone,
      as occurs in hypertension, and indicate an inherent defect in the CaR signaling
      pathway in Dahl animals, which is much more severe in DS. The method is useful in
      determining vascular reactivity ex vivo in mesenteric resistance arteries and
      similar small blood vessels and comparisons between different agonists and/or
      antagonists can be easily and consistently assessed side-by-side(6,7,8).

PMID- 21969065
TI  - The odyssey of osteoclast precursors.

PMID- 21969064
TI  - Towards the systematic exploration of chemical space.
AB  - The discovery of biologically active small molecules is shaped, in large part, by
      their synthetic (or biosynthetic accessibility). However, chemists' historical
      exploration of chemical space has been highly uneven and unsystematic. This
      article describes synthetic strategies that have emerged that may allow chemical
      space to be explored more systematically. Particular emphasis is placed on
      approaches that allow the scaffolds of small molecules to be varied
      combinatorially. In addition, some examples of bioactive small molecules that
      have been discovered by screening diverse small molecule libraries are
      highlighted. The authors comment on the likely scope of each of the strategies to
      deliver skeletally-diverse libraries. In addition, the authors highlight some key
      challenges for the future: the extension to libraries based on hundreds of
      distinct scaffolds; and the development of approaches that focus overtly on drug
      relevant chemical space.

PMID- 21969067
TI  - CPB2 dampens inflammation in autoimmune arthritis.

PMID- 21969068
TI  - Crosstalk in RA synovia-TLR3-BAFF axis sustains B-cell activation.

PMID- 21969069
TI  - Initiating fibrotic manifestations of SSc.

PMID- 21969070
TI  - Characterization of some efficient cellulase producing bacteria isolated from
      paper mill sludges and organic fertilizers.
AB  - The wide variety of bacteria in the environment permits screening for more
      efficient cellulases to help overcome current challenges in biofuel production.
      This study focuses on the isolation of efficient cellulase producing bacteria
      found in organic fertilizers and paper mill sludges which can be considered for
      use in large scale biorefining. Pure isolate cultures were screened for cellulase
      activity. Six isolates: S1, S2, S3, S4, E2, and E4, produced halos greater in
      diameter than the positive control (Cellulomonas xylanilytica), suggesting high
      cellulase activities. A portion of the 16S rDNA genes of cellulase positive
      isolates were amplified and sequenced, then BLASTed to determine likely genera.
      Phylogenetic analysis revealed genera belonging to two major Phyla of Gram
      positive bacteria: Firmicutes and Actinobacteria. All isolates were tested for
      the visible degradation of filter paper; only isolates E2 and E4 (Paenibacillus
      species) were observed to completely break down filter paper within 72 and 96 h
      incubation, respectively, under limited oxygen condition. Thus E2 and E4 were
      selected for the FP assay for quantification of total cellulase activities. It
      was shown that 1% (w/v) CMC could induce total cellulase activities of 1652.2+/
      61.5 and 1456.5+/-30.7 MUM of glucose equivalents for E2 and E4, respectively.
      CMC could induce cellulase activities 8 and 5.6X greater than FP, therefore CMC
      represented a good inducing substrate for cellulase production. The genus
      Paenibacillus are known to contain some excellent cellulase producing strains, E2
      and E4 displayed superior cellulase activities and represent excellent candidates
      for further cellulase analysis and characterization.

PMID- 21969071
TI  - A potential human hepatocellular carcinoma inhibitor from Bauhinia purpurea L.
      seeds: from purification to mechanism exploration.
AB  - A 20-kDa Kunitz-type trypsin-chymotrypsin inhibitor, Bauhinia purpurea trypsin
      inhibitor (BPLTI), has been isolated from the seeds of B. purpurea L. by using
      liquid chromatography procedures that involved ion exchange chromatography on Sp
      Sepharose and Mono S and gel filtration on Superdex 75. BPLTI demonstrated
      protease inhibitory activities of 7226 BAEE units/mg and 65 BTEE units/mg toward
      trypsin and alpha-chymotrypsin, respectively. BPLTI was relatively thermal (0-60
      degrees C) and pH (3-10) stable and its activity could be decreased by
      dithiothreitol treatment. BPLTI exhibited a wide spectrum of anti-proliferative
      and pro-apoptotic activities especially on human hepatocellular carcinoma Hep G2
      cells. However, it was devoid of a significant antiproliferative effect on
      immortal human hepatic WRL 68 cells. We show here that BPLTI stimulates apoptosis
      in Hep G2 cells, including (1) evoking DNA damage including the production of
      chromatin condensation and apoptotic bodies; (2) induction of cell
      apoptosis/necrosis; (3) mitochondrial membrane depolarization; and (4) increasing
      the production of cytokines. Taken together, our findings show for the first time
      that purified protease inhibitor from B. purpurea L. seeds is a promising
      candidate for the treatment of human hepatocellular carcinoma.

PMID- 21969072
TI  - Acute airway irritation of methyl formate in mice.
AB  - Methyl formate (MF) is a volatile solvent with several industrial applications.
      The acute airway effects of MF were evaluated in a mouse bioassay, allowing the
      assessment of sensory irritation of the upper airways, airflow limitation of the
      conducting airways and deep lung (pulmonary) irritation. MF was studied at vapour
      concentrations of 202-1,168 ppm. Sensory irritation was the only effect observed,
      which developed slowly over the 30-min exposure period. The potency at steady
      state was at least 10-fold higher than expected from a hypothetically similar,
      but non-reactive compound. Methyl formate may be hydrolysed in vivo to formic
      acid, a potent sensory irritant, and methanol, a low-potent sensory irritant.
      Hydrolysis may be catalysed by carboxyesterases, and therefore, the role of the
      esterases was studied using the esterase inhibitor tri-ortho-cresyl phosphate
      (TOCP). TOCP pre-treatment reduced the irritation response of MF, suggesting that
      carboxyesterase-mediated hydrolysis plays a role in the irritative effect.
      However, even after administration of TOCP, MF was considerably more irritating
      than expected from a quantitative structure-activity relationship (QSAR) model.
      The slope of the concentration-effect relationship for formic acid was lower than
      that for the MF in the low-dose range, suggesting that different receptor
      activation mechanisms may occur, which may include an effect of MF itself, in
      addition to an effect of formic acid and potentially an effect from formaldehyde.

PMID- 21969073
TI  - Isoeugenol destabilizes IL-8 mRNA expression in THP-1 cells through induction of
      the negative regulator of mRNA stability tristetraprolin.
AB  - We previously demonstrated in the human promyelocytic cell line THP-1 that all
      allergens tested, with the exception of the prohapten isoeugenol, induced a dose
      related release of interleukin-8 (IL-8). In the present study, we investigated
      whether this abnormal behavior was regulated by the AU-rich element-binding
      proteins HuR and tristetraprolin (TTP) or by the downstream molecule suppressor
      of cytokine signaling (SOCS)-3. The contact allergens isoeugenol, diethylmaleate
      (DEM), and 2,4-dinitrochlorobenzene (DNCB), and the irritant salicylic acid were
      used as reference compounds. Chemicals were used at concentrations that induced a
      20% decrease in cell viability as assessed by propidium iodide staining, namely
      100 MUg/ml (0.61 mM) for isoeugenol, 100 MUg/ml (0.58 mM) for DEM, 3 MUg/ml (14.8
      MUM) for DNCB, and 250 MUg/ml (1.81 mM) for salicylic acid. Time course
      experiments of IL-8 mRNA expression and assessment of IL-8 mRNA half-life,
      indicated a decreased IL-8 mRNA stability in isoeugenol-treated cells. We could
      demonstrate that a combination and regulation of HuR and TTP following exposure
      to contact allergens resulted in a different modulation of IL-8 mRNA half-life
      and release. The increased expression of TTP in THP-1 cells treated with
      isoeugenol results in destabilization of the IL-8 mRNA, which can account for the
      lack of IL-8 release. In contrast, the strong allergen DNCB failing to up
      regulate TTP, while inducing HuR, resulted in longer IL-8 mRNA half-life and
      protein release. SOCS-3 was induced only in isoeugenol-treated cells; however,
      its modulation did not rescue the lack of IL-8 release, indicating that it is
      unlikely to be involved in the lack of IL-8 production. Finally, the
      destabilization effect of isoeugenol on IL-8 mRNA expression together with SOCS-3
      expression resulted in an anti-inflammatory effect, as demonstrated by the
      ability of isoeugenol to modulate LPS or ionomycin-induced cytokine release.

PMID- 21969074
TI  - Subacute oral toxicity investigation of nanoparticulate and ionic silver in rats.
AB  - Subacute toxicity of 14 nm nanoparticulate silver (Ag-NP) stabilised with
      polyvinylpyrrolidone and ionic silver in the form of silver acetate (Ag-acetate)
      was investigated in four-week-old Wistar rats. Animals received orally by gavage
      the following: vehicle control (10 ?, 6 ?); Ag-NP at doses: 2.25 (8 ?), 4.5 (8 ?)
      or 9 mg/kg bw/day (10 ?, 6 ?); or Ag-acetate 9 mg silver/kg bw/day (8 ?) for 28
      days. Clinical, haematolological and biochemical parameters, organ weights, macro
      and microscopic pathological changes were investigated. Caecal bacterial phyla
      and their silver resistance genes were quantified. For the Ag-NP groups, no
      toxicological effects were recorded. For Ag-acetate, lower body weight gain (day
      4-7, 11-14, 14-16, P < 0.05; overall, day 1-28, P < 0.01), increased plasma
      alkaline phosphatase (P < 0.05), decreased plasma urea (P < 0.05) and lower
      absolute (P < 0.01) and relative (P < 0.05) thymus weight were recorded. In
      conclusion, these findings indicate toxicity of 9 mg/kg bw/day ionic silver but
      not of an equimolar Ag-NP dose. This is in accordance with previously reported
      data showing that oral Ag-acetate, in comparison with an equimolar dose of Ag-NP,
      resulted in higher silver plasma and organ concentrations.

PMID- 21969076
TI  - Brief report: The effect of delayed matching to sample on stimulus over
      selectivity.
AB  - Stimulus over-selectivity occurs when one aspect of the environment controls
      behavior at the expense of other equally salient aspects. Participants were
      trained on a match-to-sample (MTS) discrimination task. Levels of over
      selectivity in a group of children (4-18 years) with Autism Spectrum Disorders
      (ASD) were compared with a mental-aged matched typically-developing group. There
      was more over-selectivity in the ASD group. When retention intervals were added
      between the sample and comparisons in the MTS task, both groups showed an
      increased level of over-selectivity, with the ASD group showing a more pronounced
      effect.

PMID- 21969075
TI  - The expression of caspases is enhanced in peripheral blood mononuclear cells of
      autism spectrum disorder patients.
AB  - Autism and autism spectrum disorders (ASDs) are heterogeneous complex neuro
      developmental disorders characterized by dysfunctions in social interaction and
      communication skills. Their pathogenesis has been linked to interactions between
      genes and environmental factors. Consistent with the evidence of certain
      similarities between immune cells and neurons, autistic children also show an
      altered immune response of peripheral blood mononuclear cells (PBMCs). In this
      study, we investigated the activation of caspases, cysteinyl aspartate-specific
      proteases involved in apoptosis and several other cell functions in PBMCs from 15
      ASD children compared to age-matched normal healthy developing controls. The mRNA
      levels for caspase-1, -2, -4, -5 were significantly increased in ASD children as
      compared to healthy subjects. Protein levels of Caspase-3, -7, -12 were also
      increased in ASD patients. Our data are suggestive of a possible role of the
      caspase pathway in ASD clinical outcome and of the use of caspase as potential
      diagnostic and/or therapeutic tools in ASD management.

PMID- 21969077
TI  - Obstetrics Risk of HIV Infection among Antenatal Women in a rural Nigerian
      hospital.
AB  - BACKGROUND: Obstetrics risk and practices can lead to the spread of HIV/AIDS.
      Identification of such obstetrics risk of HIV infection is a useful step in the
      prevention of transmission of the virus.  OBJECTIVE: We sought to determine
      obstetrics risk of HIV infection in pregnant women attending antenatal clinic in
      a rural Northern Nigerian hospital.  METHODS: We conducted a cross-sectional
      descriptive study of pregnant women attending antenatal clinic of a rural mission
      hospital in northern Nigeria between June and October 2005. Data were collected
      using structured questionnaire. HIV screening and confirmation was carried out on
      pregnant women after voluntary counseling.  RESULTS: 350 pregnant women were
      enrolled with a mean age (+/-SD) of 26.8+/- 6.4years. The highest number of HIV
      infected women was observed in those who had their first coitus between 16 and 20
      years. The age at first coitus was not significantly related to the HIV infection
      (P=0.41). Neither parity (P=0.13) nor past history of abortion (P=0.42) was
      associated with HIV infection. None of the 41 women who had their last delivery
      at home had HIV infection compared with 9.8% of the 194 women who delivered in
      the hospital or clinic (P=0.008). Forty percent of those who had their last
      delivery in primary health centre had HIV infection while 22.2% of those who
      delivered under the care of traditional birth had HIV infection.  CONCLUSION:
      Obstetrics practices may encourage transmission of HIV infection. This calls for
      re-examination of the obstetrics practices especially in our primary health
      centers in order to prevent transmission of HIV infection.

PMID- 21969078
TI  - Developing treatment strategies for rare cancers.

PMID- 21969080
TI  - Resistance training vs. static stretching: effects on flexibility and strength.
AB  - Morton, SK, Whitehead, JR, Brinkert, RH, and Caine, DJ. Resistance training vs.
      static stretching: Effects on flexibility and strength. J Strength Cond Res
      25(12): 3391-3398, 2011-The purpose of this study was to determine how full-range
      resistance training (RT) affected flexibility and strength compared to static
      stretching (SS) of the same muscle-joint complexes in untrained adults.
      Volunteers (n = 25) were randomized to an RT or SS training group. A group of
      inactive volunteers (n = 12) served as a convenience control group (CON). After
      pretesting hamstring extension, hip flexion and extension, shoulder extension
      flexibility, and peak torque of quadriceps and hamstring muscles, subjects
      completed 5-week SS or RT treatments in which the aim was to stretch or to
      strength train the same muscle-joint complexes over similar movements and ranges.
      Posttests of flexibility and strength were then conducted. There was no
      difference in hamstring flexibility, hip flexion, and hip extension improvement
      between RT and SS, but both were superior to CON values. There were no
      differences between groups on shoulder extension flexibility. The RT group was
      superior to the CON in knee extension peak torque, but there were no differences
      between groups on knee flexion peak torque. The results of this preliminary study
      suggest that carefully constructed full-range RT regimens can improve flexibility
      as well as the typical SS regimens employed in conditioning programs. Because of
      the potential practical significance of these results to strength and
      conditioning programs, further studies using true experimental designs, larger
      sample sizes, and longer training durations should be conducted with the aim of
      confirming or disproving these results.

PMID- 21969079
TI  - How do they compare?: an assessment of predeployment fitness in the Arizona
      National Guard.
AB  - Currently, there is a paucity of literature that describes physical fitness
      levels in deploying service members. There has been no data collected that
      evaluate the Army National Guard or Reserves. This descriptive study will provide
      physical fitness data for soldiers in the Arizona National Guard (AZNG), allowing
      for a comparison between the active and reserve components. Sixty soldiers from
      the AZNG were tested before deployment. Body composition was measured by using
      air displacement plethysmography. Flexibility testing included the sit and reach
      (SNR), trunk extension (TE), and shoulder elevation (SE) assessments. Muscular
      strength was determined by the completion of 1 repetition maximum (1RM) bench
      press and back squat. Muscular endurance was determined by the completion of the
      Army push-up (P/U) and sit-up (S/U) test. Muscular power was assessed by the
      completion of the Wingate cycle test and the standing broad jump (SBJ).
      Cardiorespiratory fitness was determined by the completion of a VO2peak test. The
      AZNG soldiers demonstrated a fat mass of 22.7 +/- 8.9%, SNR, TE, and SE of 30.0
      +/- 8.9, 117.1 +/- 25.2, and 145.5 +/- 50.3 cm, 1RM bench press and back squat of
      82.2 +/- 29.9 and 104.6 +/- 29.0 kg, P/U and S/U of 50 +/- 18 and 53 +/- 14 reps,
      peak power of 660.9 +/- 177.8 W, SBJ of 191.8 +/- 28.4 cm, and VO2peak of 48.9 +/
      8.8 ml.kg(-1).min(-1). This is the first study that provides descriptive data
      for physical fitness in a reserve component. The data demonstrate that these AZNG
      soldiers are relatively fit and have comparable results to their active duty
      counterparts. This descriptive data will provide military leadership a better
      understanding of the condition of soldiers before deployment and will assist them
      in better preparing soldiers for future conflicts.

PMID- 21969081
TI  - Levels of muscle activation in strength and conditioning exercises and
      dynamometer hiking in junior sailors.
AB  - Although strength and conditioning exercises have been prescribed to enhance
      performance and prevent injury in sailors, little is known about these exercises
      in comparison to the demands placed on the sailor's musculature while hiking
      maximally. Because of the difficulty in collecting hiking-related data on water,
      a 3-minute maximal hiking test (HM180) has been previously developed for use in
      the laboratory setting. There were 2 aims of this study. The first aim was to
      determine whether discriminative validity could be shown for the HM180 test in a
      group of junior sailors of differing ability level and gender. The second aim was
      to determine whether differences in muscle activation existed between selected
      strength and conditioning exercises and the HM180 test. Twenty-nine adolescent
      boy and girl sailors aged between 14 and 16 years from the Singaporean National
      Byte Class training squad (n = 12) and the Singapore High Participation Group (n
      = 17) were recruited for this study. The average levels of normalized muscle
      activation in selected lower limb and trunk muscles in 4 selected strength and
      conditioning exercises (leg extension, back squat, and back extension exercises,
      a 30-second hiking hold) and a maximal 3-minute hiking test (the HM180 test) were
      quantified. Discriminative validity of the HM180 test was shown, and it was
      confirmed that the strength and conditioning exercises provide an overload
      stimulus for the HM180 test. Further, similar levels of muscle activation were
      found for the vastus lateralis in the leg extension and back squat exercises, and
      the superficial lumbar multifidus in the back extension and back squat exercises.
      This study has the potential to inform the design of strength and conditioning
      programs for junior sailors.

PMID- 21969082
TI  - NNK enhances cell migration through alpha7-nicotinic acetylcholine receptor
      accompanied by increased of fibronectin expression in gastric cancer.
AB  - BACKGROUND: In this study, we intended to dissect the mechanism of 4
      (Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-enhanced migration of gastric
      cancer. Smoking has been defined as a risk factor for gastric cancer. Tobacco
      specific carcinogen, NNK, was reported to enhance cancer progression in gastric
      cancer. Currently, metastasis is the major issue for clinical cancer therapy, but
      the influence of NNK on the migration of gastric cancer remains to be determined.
      METHODS: The expression of nicotinic receptor in gastric cancer cells was
      identified by real-time polymerase chain reaction and Western blotting. The
      influence of NNK on migration of gastric cancer cells was evaluated by the
      transwell migration assay system. Receptor-mediated migration was studied by both
      inhibitor and small interfering RNA. RESULTS: Alpha7 nicotinic acetylcholine
      receptor, alpha7-nicotinic acetylcholine receptor (nAChR), was identified higher
      than alpha9-nAChR in gastric cancer cell lines, AGS cells. NNK enhanced
      significantly gastric cancer cell migration in transwell assay. We used inhibitor
      and siRNA to demonstrate that alpha7-nAChR mediated NNK-enhanced gastric cancer
      cell migration and upregulation of fibronectin were involved in NNK-enhanced
      migration of gastric cancer cells. Finally, we found that silenced fibronectin
      expression level inhibited the migratory ability in AGS cells. CONCLUSIONS: NNK
      enhanced gastric cancer metastasis through alpha7-nAChR and fibronectin-one of
      the hallmarks of epithelial mesenchymal transition.

PMID- 21969083
TI  - Improving nodal harvest in colorectal cancer: so what?
AB  - BACKGROUND: Adequate nodal harvest (>=12 lymph nodes) in colorectal cancer has
      been shown to optimize staging and has been proposed as a quality indicator of
      colorectal cancer care. We previously demonstrated a population-based improvement
      in adequate nodal harvest over time, particularly with the use of an audit and
      feedback strategy. The goal of this current study is to evaluate the impact of
      improved adequate nodal harvest on 3 relevant clinical outcomes: node positivity
      rate, use of adjuvant chemotherapy, and survival. METHODS: This current
      population-based study included all patients undergoing resection for primary
      stage I-III colorectal cancer in Nova Scotia, Canada, from January 1, 2001 to
      December 31, 2005. Linkage of the provincial cancer registry with other
      administrative databases (hospital discharge data, physician claims data, and
      national census data) provided clinical, demographic, diagnostic, treatment
      event, and survival data. The association between increase in adequate node
      harvest and relevant clinical outcomes was examined for all patients and in a
      subgroup analysis of patients who received care in a health district that used
      audit and feedback to improve nodal harvest. RESULTS: Among the 2,250 patients,
      the median nodal harvest was 8, and the overall node positive rate was 35.9%.
      Despite significant improvement in the proportion of patients undergoing adequate
      nodal harvest over time (P<.0001), no significant change was observed in the node
      positivity rate (P=.51), proportion of patients undergoing adjuvant chemotherapy
      (P=.83), or survival (P=.25). In the subgroup analysis confined to patients where
      audit and feedback was used to improve nodal harvest rates, clinical outcomes
      were not improved. CONCLUSIONS: Although improvements in the rate of adequate
      nodal harvest did occur over time, no corresponding meaningful improvement in
      clinical outcomes was noted. Given the need that quality indicators not only be
      associated with outcome, but also that outcome improves as such indicators are
      optimized, this study questions the inclusion of a nodal harvest>=12 lymph nodes
      as a quality indicator of colorectal cancer care.

PMID- 21969084
TI  - Is one benign fine needle aspiration enough?
AB  - BACKGROUND: Fine needle aspiration (FNA) is used to diagnose thyroid nodules, but
      the follow-up of benign FNA is unclear. We sought to determine whether routine
      repeat FNAs after initial benign FNA reduces false negatives. METHODS: We
      identified 265 patients who had at least one benign FNA that either progressed to
      surgery or had at least one repeat FNA. We reviewed their ultrasonography, FNA
      cytology, and surgical pathology. RESULTS: Of 127 patients with initial benign
      FNA that had surgery, 13 had a malignancy, yielding a 10.2% false-negative rate.
      Of 22 patients who had surgery after at least two benign FNAs, one had a
      malignancy, yielding a 4.5% false-negative rate. Initially benign cytology
      (Bethesda II) was upgraded to a cytology requiring surgical intervention
      (Bethesda IV-VI) in 7 of 129 (5.4%) patients after two FNAs. Suspicious features
      on ultrasound, including size >4 cm, calcifications, or increased vascularity
      were found in 90% of patients with a false-negative FNA. CONCLUSIONS: The overall
      false-negative rate of thyroid FNAs is 10.2%, which is reduced to 4.5% with a
      second benign FNA. Ninety percent of patients with a false-negative FNA had
      suspicious sonographic features. Reaspiration should be considered in patients
      with sonographically suspicious nodules.

PMID- 21969085
TI  - Favorable outcome of secondary axillary dissection in breast cancer patients with
      axillary nodal relapse.
AB  - PURPOSE: Little evidence can be found about the long-term outcome of breast
      cancer patients after axillary lymph node recurrence (ALNR) and its survival
      benefit after different kinds of management. The present study intends to
      evaluate the risk factors associated with axillary recurrence after definite
      surgery for primary breast cancer. The prognosis after ALNR and particularly
      outcome of different management methods also were studied. METHODS: We
      retrospectively reviewed data from 4,473 patients who were diagnosed with primary
      breast cancer and received surgical intervention in a single institute from
      January 1990 to December 2002. Medical files were reviewed and data on survival
      were updated annually. Risk factors and prognosis of patients with axillary
      recurrence were analyzed. Breast-cancer-specific survival of patients with ALNR
      and outcomes after different management methods also were studied. RESULTS: After
      a median follow-up of 70.2 months, axillary recurrence developed in 0.8% of
      patients. Factors associated with ALNR included: age younger than 40 years,
      medial tumor location, no initial standard level I & II axillary dissection, and
      not receiving hormonal therapy. The 5-year breast-cancer-specific survival after
      ALNR was 57.9%. For patients who received further axillary dissection, the 5-year
      survival rate was 82.5% compared with 44.9% for patients who did not receive
      further dissection. CONCLUSIONS: ALNR is a rare event in treating breast cancer.
      Young age at diagnosis and medially located tumor are associated with higher
      risk, but standardized initial axillary dissection to level II and adjuvant
      hormonal therapy is protective against ALNR. In patients with ALNR, the outcome
      is not dismal and survival may be improved if further axillary dissection is
      given.

PMID- 21969086
TI  - TNFAIP8 overexpression: clinical relevance to esophageal squamous cell carcinoma.
AB  - BACKGROUND: Tumor necrosis factor alpha-induced protein 8 (TNFAIP8) is a
      suppressor of TNF-alpha mediated apoptosis, and its expression is induced by NF
      kappaB activation. TNFAIP8 expression is significantly increased in various
      cancer cell lines. A correlation between TNFAIP8 overexpression, cancer
      progression, and poor prognosis has been described in many reports of human solid
      cancers. METHODS: To clarify the functional and clinical significance of the
      cancer progression-related gene, TNFAIP8, in esophageal squamous cell carcinoma
      (ESCC), we used immunohistochemistry to demonstrate TNFAIP8 expression in ESCC.
      Next, TNFAIP8 expression was depleted by using siRNA to examine the function of
      TNFAIP8 in the proliferation and apoptosis induction of ESCC cell lines. RESULTS:
      We detected correlations between TNFAIP8 expression and TNM stage (P < 0.001),
      tumor depth (P = 0.002), lymph node metastasis (P = 0.013), distant metastasis (P
      = 0.001), lymphatic invasion (P < 0.001), and venous invasion (P < 0.001) among
      the clinicopathological characteristics of ESCC patients, and high TNFAIP8
      expression was found in poor survival. TNFAIP8 depletion was significantly
      associated with apoptosis induction after cisplatin administration and reduced
      proliferation. CONCLUSIONS: Our results suggest that TNFAIP8 might be an
      effective therapeutic target for ESCC in the future.

PMID- 21969087
TI  - Oncoantigens for an immune prevention of cancer.
AB  - Vaccines are one of the main arms of preventive medicine. Recently a large series
      of experiments with cancer-prone genetically engineered mice have shown that
      preventive vaccines are also extremely efficacious inhibitors of the progression
      of carcinogenesis. Early vaccination affords significant and persistent
      protection, whereas its efficacy fades when neoplastic lesions become more
      advanced. Our current attempts to use combination strategies and technological
      advances to make vaccines effective in cancer prevention able to cure more
      advanced stages of cancer lesions are based on the temporary and systemic T(reg)
      removal, the preparation of new bimodular plasmids for DNA vaccination, and the
      search for fresh target oncoantigens.

PMID- 21969088
TI  - Understanding appraisal processes underlying the thentest: a mixed methods
      investigation.
AB  - AIMS: Mixed methods investigated the cognitive processes reflected in
      retrospective pretest (thentest) discrepancy scores [i.e., recalibration response
      shift (RS)]. METHODS: People with human immunodeficiency virus/acquired immune
      disease syndrome (HIV/AIDS) (n = 521) were interviewed at baseline and 6 months
      using the Quality of Life (QOL) Appraisal Profile, the Rand-36, General Health
      thentest, and recall items. Open-ended appraisal questions were coded, and factor
      analyses reduced the data. Ipsative (based on the then-minus-pretest) and
      normative (based on regression residuals) discrepancy scores were compared.
      Hypothesis testing related to recall bias and relationships among appraisal
      parameters and ipsative discrepancies, after covariate adjustment. RESULTS: Coded
      frame of reference themes were distinct from experience sampling, standards of
      comparison, and combinatory algorithm. There was convergence between the ipsative
      and normative discrepancy scores (r = 0.30), but the former were associated with
      more appraisal changes and goal-related appraisals than the latter. Thentest
      effect sizes (ES) were larger than standard change scores, even controlling for
      recall bias. Multivariate models including appraisal parameters explained 9% more
      variance over the standard (unadjusted for RS) model. CONCLUSIONS: Ipsative and
      normative discrepancy scores measure distinct constructs, represent different
      configurations of appraisal change, and are not invalidated or explained by
      recall bias. The thentest does not imply recalibration alone but rather a host of
      health- and self-care-related concerns.

PMID- 21969090
TI  - Suggestions for enhancing training in pediatric forensic pathology: a trainee's
      perspective.

PMID- 21969089
TI  - Arabidopsis MKKK20 is involved in osmotic stress response via regulation of MPK6
      activity.
AB  - Plants have developed various regulatory pathways to adapt to environmental
      stresses. In this study, we identified Arabidopsis MKKK20 as a regulator in the
      response to osmotic stress. mkkk20 mutants were found to be sensitive to high
      concentration of salt and showed higher water loss rates than wild-type (WT)
      plants under dehydration conditions. In addition, mkkk20 mutants showed higher
      accumulation of superoxide, a reactive oxygen species (ROS), compared to WT
      plants under high salt condition. In contrast, transgenic plants overexpressing
      MKKK20 displayed tolerance to salt stress. MKKK20 transcripts were increased by
      the treatments with NaCl, mannitol, MV, sorbitol, and cold, suggesting that
      MKKK20 is involved in the response to osmotic, ROS, and cold stresses. In-gel
      kinase assay showed that MKKK20 regulates the activity of MPK6 under NaCl, cold,
      and H(2)O(2) treatments. Taken together, our results suggest that MKKK20 might be
      involved in the response to various abiotic stresses, especially osmotic stress,
      through its regulation of MPK6 activity.

PMID- 21969091
TI  - Mean platelet volume as a marker of increased cardiovascular risk in patients
      with nonalcoholic steatohepatitis.

PMID- 21969092
TI  - Toll-like receptor 4 expression on circulating leucocytes in hemolytic uremic
      syndrome.
AB  - Lipopolysaccharide stimulation of toll-like receptor 4 (TLR4) activates signal
      transduction pathways leading to proinflammatory cytokine secretion. We
      investigated TLR4 surface receptor expression on peripheral blood neutrophils and
      monocytes and their ability to modulate inflammatory cytokine release in 15
      patients 1, 3, and 10 days after hemolytic uremic syndrome (HUS) onset. Seven
      patients with Escherichia coli (EHEC)-associated diarrhea and seven healthy
      controls were also studied. Isolated leucocytes from HUS-onset patients exhibited
      significantly higher messenger RNA (mRNA) TLR4 expression than controls.
      Moreover, TLR4 protein expression on neutrophils, determined by flow cytometry,
      was upregulated, driving dependent proinflammatory cytokine, tumor necrosis
      factor alpha (TNF-alpha), and interleukin 8 (IL-8) increase, and decreased anti
      inflammatory IL-10 release at HUS onset compared with patients with EHEC diarrhea
      and controls. TLR4 expression on neutrophils was positively correlated with serum
      TNF-alpha levels. Conversely, significant reduction of neutrophil TLR4 receptor
      expression and lack of cytokine-responsive element activation was shown in
      patients 3 and 10 days after HUS onset. No differences were demonstrated in TLR4
      receptor expression on monocytes among the studied groups. Our results suggest
      TLR4 expression may be differently regulated on neutrophils and monocytes. They
      could be dynamically modulated across the early development of HUS on
      neutrophils, resulting in negative regulation preceded by TLR4 overactivation.

PMID- 21969093
TI  - Matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 in
      vesicoureteral reflux.
AB  - The aim of this study was to investigate whether urine levels of matrix
      metalloproteinase 9 (uMMP9) and tissue inhibitor of metalloproteinase 1 (uTIMP1)
      are novel biomarkers of vesicoureteral reflux (VUR) and to determine the optimal
      cut-off levels of these enzymes to predict VUR in children. The study group
      consisted of 67 children with VUR and 20 healthy children. Urine MMP9 and TIMP1
      levels were measured by an enzyme-linked immunosorbent assay. Children with VUR
      had significantly higher uMMP9 (1,539.8 vs. 256.4 pg/mL; p = 0.0001) and uTIMP1
      (182 vs. 32.6 pg/mL; p = 0.0001) levels than healthy children. For the prediction
      of VUR, the sensitivity of uMMP9 was 67%, with a specificity of 85% [cut-off
      value 1,054 pg/mL; area under the curve (AUC) 0.77], and the sensitivity of
      uTIMP1 was 74%, with a specificity of 65% (cut-off value 18.7 pg/mL; AUC 0.73).
      Both uMMP9 and uTIMP1 levels were significantly higher in patients with renal
      scar (uMMP9: 3,117.3 vs. 1,234.15 pg/mL; p = 0.0001; uTIMP1: 551.05 vs. 128.64
      pg/mL; p = 0.0001). Urine MMP9 levels had a sensitivity of 81.2%, with a
      specificity of 85% to predict renal scar in the VUR group (cut-off 1,054 pg/mL;
      AUC 0.88). The sensitivity of uTIMP1 was 75%, with a specificity of 90% to
      predict renal scar (cut-off 243.7 pg/mL; AUC 0.82). Based on these results, we
      suggest that uTIMP1 may be a useful marker to predict renal scarring with a
      different cut-off value from VUR and a high specificity at this cut-off point.
      Although uMMP9 seemingly cannot distinguish renal scar from VUR, the simultaneous
      increase in the level of both markers may indicate ongoing renal injury due to
      VUR.

PMID- 21969094
TI  - Prevalence of lower urinary tract symptoms in school-age children.
AB  - Epidemiological studies have demonstrated rates of incontinence and enuresis as
      high as 20% in school-age children. This cross-sectional study aimed to
      investigate the prevalence of lower urinary tract (LUT) symptoms in 739 children
      aged 6-12 years enrolled in three government schools with different socioeconomic
      levels in Minas Gerais, Brazil. Symptoms of LUT were evaluated using a modified
      version of the Dysfunction Voiding Scoring System in which the cutoff point
      considered as an indicator of LUT dysfunction is >6 for girls and >9 for boys.
      Children with a score indicative of symptoms received an educational booklet on
      the functioning of the LUT and were sent for clinical evaluation. LUT dysfunction
      symptoms were detected in 161 (21.8%) children. Symptoms were most frequent in
      girls (p < 0.001), children aged 6-8 (p < 0.028), and attended the school with
      the lowest social level (p < 0.001). Intestinal constipation was the most
      prevalent finding (30.7%), independent of LUT score. The most common urinary
      symptoms in children with an elevated score were diurnal urinary incontinence
      (30.7%), holding maneuvers (19.1%), and urinary urgency (13.7%). Stress factors
      were associated in 28.4% of children. Our findings suggest that LUT symptoms must
      be investigated carefully at routine pediatric visits.

PMID- 21969095
TI  - Imaging G-protein coupled receptor (GPCR)-mediated signaling events that control
      chemotaxis of Dictyostelium discoideum.
AB  - Many eukaryotic cells can detect gradients of chemical signals in their
      environments and migrate accordingly (1).  This guided cell migration is referred
      as chemotaxis, which is essential for various cells to carry out their functions
      such as trafficking of immune cells and patterning of neuronal cells (2, 3).  A
      large family of G-protein coupled receptors (GPCRs) detects variable small
      peptides, known as chemokines, to direct cell migration in vivo (4).  The final
      goal of chemotaxis research is to understand how a GPCR machinery senses
      chemokine gradients and controls signaling events leading to chemotaxis.  To this
      end, we use imaging techniques to monitor, in real time, spatiotemporal
      concentrations of chemoattractants, cell movement in a gradient of
      chemoattractant, GPCR mediated activation of heterotrimeric G-protein, and
      intracellular signaling events involved in chemotaxis of eukaryotic cells (5-8). 
      The simple eukaryotic organism, Dictyostelium discoideum, displays chemotaxic
      behaviors that are similar to those of leukocytes, and D. discoideum is a key
      model system for studying eukaryotic chemotaxis.  As free-living amoebae, D.
      discoideum cells divide in rich medium.  Upon starvation, cells enter a
      developmental program in which they aggregate through cAMP-mediated chemotaxis to
      form multicullular structures.  Many components involved in chemotaxis to cAMP
      have been identified in D. discoideum.  The binding of cAMP to a GPCR (cAR1)
      induces dissociation of heterotrimeric G-proteins into Ggamma and Gbetagamma
      subunits (7, 9, 10).  Gbetagamma subunits activate Ras, which in turn activates
      PI3K, converting PIP(2;) into PIP(3;) on the cell membrane (11-13).  PIP(3;)
      serve as binding sites for proteins with pleckstrin Homology (PH) domains, thus
      recruiting these proteins to the membrane (14, 15).  Activation of cAR1 receptors
      also controls the membrane associations of PTEN, which dephosphorylates PIP(3;)
      to PIP(2;)(16, 17).  The molecular mechanisms are evolutionarily conserved in
      chemokine GPCR-mediated chemotaxis of human cells such as neutrophils (18).  We
      present following methods for studying chemotaxis of D. discoideum cells.  1.
      Preparation of chemotactic component cells. 2. Imaging chemotaxis of cells in a
      cAMP gradient.  3. Monitoring a GPCR induced activation of heterotrimeric G
      protein in single live cells.  4. Imaging chemoattractant-triggered dynamic
      PIP(3;) responses in single live cells in real time.  Our developed imaging
      methods can be applied to study chemotaxis of human leukocytes.

PMID- 21969096
TI  - Refractory hypotension in a patient with Wernicke's encephalopathy.
AB  - A 57-year-old male patient with gastric carcinoma underwent radical distal
      gastrectomy type II + Braun anastomosis, and received total parenteral nutrition
      for 10 days after surgery, followed by small amounts of semi-liquid nutrition for
      3 days and liquid nutrition for 2 days. The patient developed refractory
      hypotension for more than 1 week in the early course of disease, and on Day 15
      after surgery presented with characteristic signs of Wernicke's encephalopathy,
      including diplopia and mental confusion. The hypotension did not improve despite
      appropriate fluid replacement soon after admission. Treatment with moderate dose
      of thiamine for 3 months partly relieved ophthalmoplegia and confusion, but not
      Korsakoff syndrome. This extraordinary presentation with refractory hypotension
      and the unusual course of the disease encouraged us to present this case.

PMID- 21969097
TI  - Impact of Triticum mosaic virus infection on hard winter wheat milling and bread
      baking quality.
AB  - BACKGROUND: Triticum mosaic virus (TriMV) is a newly discovered wheat virus.
      Information regarding the effect of wheat viruses on milling and baking quality
      is limited. The objective of this study was to determine the impact of TriMV
      infection on the kernel characteristics, milling yield and bread baking quality
      of wheat. Commercial hard winter varieties evaluated included RonL, Danby and
      Jagalene. The TriMV resistance of RonL is low, while that of Danby and Jagalene
      is unknown. KS96HW10-3, a germplasm with high TriMV resistance, was included as a
      control. Plots of each variety were inoculated with TriMV at the two- to three
      leaf stage. Trials were conducted at two locations in two crop years. RESULTS:
      TriMV infection had no effect on the kernel characteristics, flour yield or
      baking properties of KS96HW10-3. The effect of TriMV on the kernel
      characteristics of RonL, Danby and Jagalene was not consistent between crop years
      and presumably an environmental effect. The flour milling and bread baking
      properties of these three varieties were not significantly affected by TriMV
      infection. CONCLUSION: TriMV infection of wheat plants did not affect harvested
      wheat kernel characteristics, flour milling properties or white pan bread baking
      quality.

PMID- 21969098
TI  - Nucleosomes structure and dynamics: effect of CHAPS.
AB  - Dynamics of nucleosomes and spontaneous unwrapping of DNA are fundamental
      property of the chromatin enabling access to nucleosomal DNA for regulatory
      proteins. Probing of such dynamics of nucleosomes performed by single molecule
      techniques revealed a large scale dynamics of nucleosomes including their
      spontaneous unwrapping. Dissociation of nucleosomes at low concentrations is a
      complicating issue for studies with single molecule techniques. In this paper, we
      tested the ability of 3-[(3-Cholamidopropyl)dimethylammonio]-l-propanesulfonate
      (CHAPS) to prevent dissociation of nucleosomes. The study was performed with
      mononucleosome system assembled with human histones H2A, H2B, H3 and H4 on the
      DNA substrate containing sequence 601 that provides the sequencespecific assembly
      of nucleosomes. We used Atomic Force Microscopy (AFM) to directly identify
      nucleosomes and analyze their structure at the nanometer level. These studies
      showed that in the presence of CHAPS at millimolar concentrations, nucleosomes,
      even at sub-nanomolar concentrations, remain intact over days compared to a
      complete dissociation of the same nucleosome sample over 10 min in the absence of
      CHAPS. Importantly, CHAPS does not change the conformation of nucleosomes as
      confirmed by the AFM analysis. Moreover, 16 uM CHAPS stabilizes nucleosomes in
      over one hour incubation in the solution containing as low as 0.4 nM in
      nucleosomes. The stability of nucleosomes is slightly reduced at physiological
      conditions (150 mM NaCl), although the nucleosomes dissociate rapidly at 300 mM
      NaCl. The sequence specificity of the nucleosome in the presence of CHAPS
      decreased suggesting that the histone core translocates along the DNA substrate
      utilizing sliding mechanism.

PMID- 21969099
TI  - Tegaserod in the treatment of constipation-predominant irritable bowel syndrome.
      Do the risks outweigh the benefits?

PMID- 21969100
TI  - Cu(I)-catalyzed tandem benzyldiazoester coupling with terminal alkyne-allene
      formation-Michael reaction: application to the syntheses of oxa and azacycles.
AB  - A simple and practical procedure for the synthesis of aza- and oxacycles, which
      possess an array of stereogenic functionalities, is described. This protocol
      relies on tandem Cu-catalyzed coupling of suitably functionalized terminal alkyne
      with diazoester followed by isomerization and subsequent aza or oxa-Michael
      reaction, thus generating the required scaffold with high diastereoselectivity.

PMID- 21969101
TI  - Characterization of the melanocortin-4-receptor nonsense mutation W16X in vitro
      and in vivo.
AB  - Several genetic diseases are triggered by nonsense mutations leading to the
      formation of truncated and defective proteins. Aminoglycosides have the
      capability to mediate a bypass of stop mutations during translation thus
      resulting in a rescue of protein expression. So far no attention has been
      directed to obesity-associated stop mutations as targets for nonsense
      suppression. Herein, we focus on the characterization of the melanocortin-4
      receptor (MC4R) nonsense allele W16X identified in obese subjects. Cell culture
      assays revealed a loss-of-function of Mc4r(X16) characterized by impaired surface
      expression and defect signaling. The aminoglycoside G-418 restored Mc4r(X16)
      function in vitro demonstrating that Mc4r(X16) is susceptible to nonsense
      suppression. For the evaluation of nonsense suppression in vivo, we generated a
      Mc4r(X16) knock-in mouse line by gene targeting. Mc4r(X16) knock-in mice
      developed hyperphagia, impaired glucose tolerance, severe obesity and an
      increased body length demonstrating that this new mouse model resembles typical
      characteristics of Mc4r deficiency. In a first therapeutic trial, the
      aminoglycosides gentamicin and amikacin induced no amelioration of obesity.
      Further experiments with Mc4r(X16) knock-in mice will be instrumental to
      establish nonsense suppression for Mc4r as an obesity-associated target gene
      expressed in the central nervous system.

PMID- 21969103
TI  - High sensitivity (1 ppm) hydrogen detection using an unconventional Pd/n-InP
      Schottky device.
AB  - Hydrogen is detected using a Pd/n-InP Schottky diode in which the elongated, very
      thin Pd electrode is of greater resistance than the underlying semiconductor
      substrate. Four-probe measurements of the device resistance, as a function of
      hydrogen concentration, are made by contacting only the Pd electrode, with a
      sensitivity of 1 ppm being achieved. On hydrogen exposure the device resistance
      drops from an initial high value, characteristic of the Pd electrode alone, to a
      lower value due to a hydrogen-induced lowering of the Schottky barrier that opens
      up the InP substrate as a parallel current carrying channel.

PMID- 21969102
TI  - Binding of novel fullerene inhibitors to HIV-1 protease: insight through
      molecular dynamics and molecular mechanics Poisson-Boltzmann surface area
      calculations.
AB  - The objectives of this study include the design of a series of novel fullerene
      based inhibitors for HIV-1 protease (HIV-1 PR), by employing two strategies that
      can also be applied to the design of inhibitors for any other target.
      Additionally, the interactions which contribute to the observed exceptionally
      high binding free energies were analyzed. In particular, we investigated: (1)
      hydrogen bonding (H-bond) interactions between specific fullerene derivatives and
      the protease, (2) the regions of HIV-1 PR that play a significant role in
      binding, (3) protease changes upon binding and (4) various contributions to the
      binding free energy, in order to identify the most significant of them. This
      study has been performed by employing a docking technique, two 3D-QSAR models,
      molecular dynamics (MD) simulations and the molecular mechanics Poisson-Boltzmann
      surface area (MM-PBSA) method. Our computed binding free energies are in
      satisfactory agreement with the experimental results. The suitability of specific
      fullerene derivatives as drug candidates was further enhanced, after ADMET
      (absorption, distribution, metabolism, excretion and toxicity) properties have
      been estimated to be promising. The outcomes of this study revealed important
      protein-ligand interaction patterns that may lead towards the development of
      novel, potent HIV-1 PR inhibitors.

PMID- 21969104
TI  - Correlations of Radiographic Findings in Patients with Low Back Pain.
AB  - BACKGROUND: Low back pain can cause severe debilitating pain that may lead to
      loss of productivity. The pain is usually non-specific and imaging request
      protocols varies. However, physicians may order lumbo-sacral x-ray in the initial
      radiologic assessment of the patient. This study aims to determine the frequency
      of occurrence of radiographic findings in patients reporting low back pain
      including the presence of osteophytes, spondylolisthesis and degenerative disc
      diseases and determine the relationship with patients' features including age,
      sex, marital status, level of education, body mass index and other radiographic
      findings.  METHOD: Patients who presented at our department for radiographic
      assessment of the lumbo-sacral spine were voluntarily recruited. Their
      radiographs were reviewed and questionnaire administered. Height and weight were
      measured. The radiographic findings were documented and data analysis using Chi
      square with significant level set at p < 0.05.  RESULT: Lumbo-sacral x-rays of
      337 patients were reviewed with more females than males, ratio 1:1.4. Osteophytes
      were demonstrable in 73.6%; spondylolisthesis, 13.4%; and disc degeneration,
      28.2%. Disc degeneration correlated with age, educational status, osteophytosis,
      osteopenia and spondylolisthesis. Osteophytosis correlated with age, BMI and
      educational level. While spondylolisthesis correlated with educational level and
      sex.  CONCLUSION: Osteophytosis was the commonest finding in patients presenting
      with LBP. Disc degeneration shows a strong association with osteophytosis and
      spondylolisthesis and it is reported to herald these changes. Radiography still
      shows some correlations between the findings in LBP and patients'
      characteristics.

PMID- 21969105
TI  - Effects of amisulpride and aripiprazole on progressive-ratio schedule
      performance: comparison with clozapine and haloperidol.
AB  - Clozapine and some other atypical antipsychotics (e.g. quetiapine, olanzapine)
      have been found to exert a characteristic profile of action on operant behaviour
      maintained by progressive-ratio schedules, as revealed by Killeen's Mathematical
      Principles of Reinforcement model of schedule-controlled behaviour. These drugs
      increase the value of a parameter that expresses the 'incentive value' of the
      reinforcer (a) and a parameter that is inversely related to the organism's 'motor
      capacity' (delta). This experiment examined the effects of two further atypical
      antipsychotics, aripiprazole and amisulpride, on progressive-ratio schedule
      performance in rats; the effects of clozapine and a conventional antipsychotic,
      haloperidol, were also examined. In agreement with previous findings, clozapine
      (4, 8 mg kg-1) increased a and delta, whereas haloperidol (0.05, 0.1 mg kg-1)
      reduced a and increased delta. Aripiprazole (3,30 mg kg-1) increased delta but
      did not affect a. Amisulpride (5, 50 mg kg-1) had a delayed and protracted
      effect: delta was increased 3-6 hours after treatment; a was increased 1.5 hours,
      and reduced 12-24 hours after treatment. Interpretation based on Killeen's model
      suggests that aripiprazole does not share clozapine's ability to enhance
      reinforcer value. Amisulpride produced a short-lived enhancement, followed by a
      long-lasting reduction, of reinforcer value. Both drugs impaired motor
      performance.

PMID- 21969106
TI  - Pharmacogenetic studies of change in cortisol on ecstasy (MDMA) consumption.
AB  - In this study we investigate the association of cytochrome P450 enzyme CYP2D6,
      catechol-O-methyl transferase (COMT, Val158Met) and serotonin transporter
      promoter (5-HTTLPR) genotypes on change in cortisol concentration following 3, 4
      methylenedioxy-methamphetamine (MDMA, 'ecstasy') consumption. Forty-eight
      subjects (30 males, mean age 23 years), self-nominating regular clubbers provided
      'in the field' pre- and post-clubbing biological samples and associated
      information. Of the 39 subjects who provided a post-clubbing urine sample, 21
      were positive for MDMA. Plasma cortisol concentrations increased in subjects (n =
      48) tested for cortisol, with changes being significantly greater in the MDMA
      positive group (736.9 +/- 83.2 vs. 350.9 +/- 34.5 mmol/l, p = 0.001). We found a
      positive association between the low activity COMT genotype (Met/Met) and MDMA
      induced change in cortisol and also between this and change in cortisol in the
      whole sample (p = 0.039, Bonferroni corrected). For CYP2D6, there was an
      association between genotype and change in cortisol, confined to subjects with
      MDMA-positive urine post-clubbing (p = 0.003, Bonferroni corrected). There was no
      association with 5-HTTLPR genotype. These associations suggest that chronic use
      of MDMA may lead to HPA axis dysregulation and that the magnitude of this may be
      moderated by genetic polymorphism, and warrant further investigation in a larger
      sample of those who consume the drug on a regular basis.

PMID- 21969107
TI  - Therapy of adrenocortical cancer: present and future.
AB  - Adrenocortical carcinoma is a rare endocrine malignancy with an estimated
      worldwide incidence of 0.5 - 2 per million/year. This neoplasm is characterized
      by a high risk of recurrence and a dismal prognosis owing to unsatisfactory
      overall survival. Surgery represents the cornerstone of adrenocortical carcinoma
      therapy, which can be associated to radiotherapy and adjuvant mitotane
      administration. In advanced cases, different chemotherapy regimens are used, but
      their relative efficacy is still unknown until the results of clinical trials
      under way will be published. Novel drugs have been recently developed based on
      the discovery of molecular pathways that trigger development and evolution of
      these tumors. More efficient treatments are widely expected in the future from
      these new targeted therapies as a hope of cure for patients affected with this
      aggressive malignancy.

PMID- 21969108
TI  - Complexity analysis of resting-state MEG activity in early-stage Parkinson's
      disease patients.
AB  - The aim of the present study was to analyze resting-state brain activity in
      patients with Parkinson's disease (PD), a degenerative disorder of the nervous
      system. Magnetoencephalography (MEG) signals were recorded with a 151-channel
      whole-head radial gradiometer MEG system in 18 early-stage untreated PD patients
      and 20 age-matched control subjects. Artifact-free epochs of 4 s (1250 samples)
      were analyzed with Lempel-Ziv complexity (LZC), applying two- and three-symbol
      sequence conversion methods. The results showed that MEG signals from PD patients
      are less complex than control subjects' recordings. We found significant group
      differences (p-values <0.01) for the 10 major cortical areas analyzed (e.g.,
      bilateral frontal, central, temporal, parietal, and occipital regions). In
      addition, using receiver-operating characteristic curves with a leave-one-out
      cross-validation procedure, a classification accuracy of 81.58% was obtained. In
      order to investigate the best combination of LZC results for classification
      purposes, a forward stepwise linear discriminant analysis with leave-one out
      cross-validation was employed. LZC results (three-symbol sequence conversion)
      from right parietal and temporal brain regions were automatically selected by the
      model. With this procedure, an accuracy of 84.21% (77.78% sensitivity, 90.0%
      specificity) was achieved. Our findings demonstrate the usefulness of LZC to
      detect an abnormal type of dynamics associated with PD.

PMID- 21969109
TI  - Highly sensitive and selective cyanide detection via Cu2+ complex ligand
      exchange.
AB  - A new type of fluorescent probe (1) with two triazole groups that are conjugated
      with a carbazole moiety was synthesized by a Cu(I)-catalyzed alkyne-azide click
      reaction for the selective and sensitive detection of cyanide via fluorescence
      enhancement by ligand exchange and metal ion removal.

PMID- 21969111
TI  - Geophagy in chacma baboons: patterns of soil consumption by age class, sex, and
      reproductive state.
AB  - Despite baboons' widespread distribution across Africa, geophagy among all
      subspecies has been poorly documented. We used video camera traps and soil
      analyses to investigate geophagy in chacma baboons (Papio cynocephalus ursinus)
      inhabiting the Western Cape of South Africa. During an 18-month study, from
      August 2009 to January 2011, we continually monitored the largest and most
      frequently visited geophagy sites with camera traps for 545 days and captured
      soil consumption at one or more sites on 266 of those days (49%). In 3,500 baboon
      visits to geophagy sites, video camera traps captured 58.6 hr of geophagy. From
      these data, we evaluated site preference based on time spent consuming soil among
      these four geophagy sites. One hundred and seventy days of soil consumption data
      from the most frequently visited geophagy site allowed us to look for demographic
      trends in geophagy. Selected consumed soils from geophagy sites were analyzed for
      mineral, physical, and chemical properties. The baboons spent more time consuming
      white alkaline soils with high percentages of clay and fine silt, which contained
      higher concentrations of sodium than non-white acidic soils that contained higher
      concentrations of iron. Our data indicate that pregnant chacma baboons spent more
      time consuming soil at monitored geophagy sites than baboons of any other age
      class, sex, or reproductive state. Based on analytical results, the soils
      consumed would be effective at alleviating gastrointestinal distress and possibly
      supplementing minerals for all age/sex classes, but potentially for different
      age/sex requirements.

PMID- 21969110
TI  - Integrated imaging of non-small cell lung cancer recurrence: CT and PET-CT
      findings, possible pitfalls and risk of recurrence criteria.
AB  - OBJECTIVES: To review the role of imaging in the diagnosis of recurrent disease
      in previously treated non-small cell lung cancer (NSCLC) and discuss the imaging
      pitfalls. METHODS: A comprehensive review of published literature on CT and PET
      imaging of NSCLC recurrence was performed. Diagnostic and prognostic values are
      discussed. Representative imaging examples are illustrated. RESULTS: Up to 30% of
      NSCLC recurrences present as loco-regional, involving treated hemithorax and
      ipsilateral lymph nodes, while 70% present as metachronous distant metastases. CT
      and PET-CT play an important role in the early detection of recurrence;
      indications for imaging vary depending on pathological features. CONCLUSION:
      Imaging plays a central role in the identification of recurrence and may predict
      prognosis. KEY POINTS: Lung cancer recurs after surgery in 30% to 75% of
      patients. CT and PET-CT are crucial in identification of loco-regional
      recurrence. Knowledge of potential pitfalls is essential, especially for
      parenchymal or nodal recurrence. CT can diagnose metastases but further
      examinations (PET-CT, MRI) are often needed. Morphological and functional imaging
      criteria may help in predicting recurrence.

PMID- 21969112
TI  - Patterns of leaf morphology and leaf N content in relation to winter temperatures
      in three evergreen tree species.
AB  - The competitive equilibrium between deciduous and perennial species in a new
      scenario of climate change may depend closely on the productivity of leaves along
      the different seasons of the year and on the morphological and chemical
      adaptations required for leaf survival during the different seasons. The aim of
      the present work was to analyze such adaptations in the leaves of three evergreen
      species (Quercus ilex, Q. suber and Pinus pinaster) and their responses to
      between-site differences in the intensity of winter harshness. We explore the
      hypothesis that the harshness of winter would contribute to enhancing the leaf
      traits that allow them to persist under conditions of stress. The results
      revealed that as winter harshness increases a decrease in leaf size occurs in all
      three species, together with an increase in the content of nitrogen per unit leaf
      area and a greater leaf mass per unit area, which seems to be achieved only
      through increased thickness, with no associated changes in density. P. pinaster
      was the species with the most intense response to the harshening of winter
      conditions, undergoing a more marked thickening of its needles than the two
      Quercus species. Our findings thus suggest that lower winter temperatures involve
      an increase in the cost of leaf production of evergreen species, which must be
      taken into account in the estimation of the final cost and benefit balance of
      evergreens. Such cost increases would be more pronounced for those species that,
      like P. pinaster, show a stronger response to the winter cold.

PMID- 21969113
TI  - Optimized quantities of GDNF overexpressed by engineered astrocytes are critical
      for protection of neuroblastoma cells against 6-OHDA toxicity.
AB  - Optimized levels of glial cell line-derived neurotrophic factor (GDNF) are
      critical for protection of dopaminergic neurons against parkinsonian cell death.
      Recombinant lentiviruses harboring GDNF coding sequence were constructed and used
      to infect astrocytoma cell line 1321N1. The infected astrocytes overexpressed
      GDNF mRNA and secreted an average of 2.2 ng/mL recombinant protein as tested in
      both 2 and 16 weeks post-infection. Serial dilutions of GDNF-enriched conditioned
      medium from infected astrocytes added to growing neuroblastoma cell line SK-N-MC
      resulted in commensurate resistance against 6-OHDA toxicity. SK-N-MC cell
      survival rate rose from 51% in control group to 84% in the cells grown with astro
      CM containing 453 pg secreted GDNF, an increase that was highly significant (P <
      0.0001). However, larger volumes of the GDNF-enriched conditioned medium failed
      to improve cell survival and addition of volumes that contained 1,600 pg or more
      GDNF further reduced survival rate to below 70%. Changes in cell survival
      paralleled to changes in the percent of apoptotic cell morphologies. These data
      demonstrate the feasibility of using astrocytes as minipumps to stably
      oversecrete neurotrophic factors and further indicate that GDNF can be applied to
      neuroprotection studies in PD pending the optimization of its concentrations.

PMID- 21969114
TI  - Mechanisms for endothelial monocyte-activating polypeptide-II-induced opening of
      the blood-tumor barrier.
AB  - Endothelial monocyte-activating polypeptide-II (EMAP-II) increases blood-tumor
      barrier (BTB) permeability by inducing alterations in the tight junction (TJ)
      complex between brain endothelial cells. In the present study, an in vitro BTB
      model was used to search for the interacting and functional cell surface molecule
      of EMAP-II as well as the signaling pathway involved in the EMAP-II-induced BTB
      hyperpermeability. Our results revealed that EMAP-II-induced increase in BTB
      permeability and down-regulation of TJ-related proteins occludin and ZO-1 were
      associated with its binding to ATP synthase alpha subunit (alpha-ATP synthase) on
      the surface of rat brain microvascular endothelial cells (BMECs). In addition, we
      observed that EMAP-II administration activated protein kinase C (PKC) and induced
      the translocation of PKC from the cytosolic to the membrane fraction of BMECs.
      The effects of EMAP-II on BTB permeability as well as expression levels of
      occludin and ZO-1 in BMECs were significantly diminished by H7, the inhibitor of
      PKC. In summary, these data suggest that EMAP-II increases BTB permeability
      through alpha-ATP synthase on the surface of BMECs, and PKC signaling pathway
      might be involved in this process.

PMID- 21969115
TI  - Bioenhancing and antimycobacterial agents from Ammannia multiflora.
AB  - The methanolic extract of Ammannia multiflora (Lythraceae) showed significant
      bioenhancing activity with the antibiotic nalidixic acid. Bioassay-guided
      fractionation of MeOH extract resulted in the isolation of a novel compound, 2,5
      bis-(3,3'-hydroxyaryl)tetrahydrofuran, named as ammaniol (5), along with 9 other
      known compounds (1-4, 6-10). Furthermore, compound 4-hydroxy- alpha-tetralone (1)
      was converted into five semisynthetic acyl derivatives, 1A-1E, which were
      evaluated along with compounds 1, 5, 6, 9, and 10 for their bioenhancing activity
      in combination with nalidixic acid against the two strains, CA8000 and DH5 alpha,
      of Escherichia coli. The results showed that the methanolic extract of A.
      multiflora and compounds 1 and 9 possessed significant bioenhancing activity and
      reduced the dose of nalidixic acid fourfold while compounds 5, 6, 10 and
      semisynthetic derivatives 1A- 1E reduced the dose of nalidixic acid twofold.
      Compound 5 was also tested for antimycobacterial activity against Mycobacterium
      H37Rv and was found to show moderate activity (MIC 25 ug/mL) against this
      pathogen.

PMID- 21969116
TI  - Neuraminidase inhibitory polyketides from the marine-derived fungus Phoma
      herbarum.
AB  - Two new polyketides, arthropsadiol C (1) and massarilactone H (2), together with
      six known derivatives (3-8) were isolated from the culture broth of the marine
      derived fungus Phoma herbarum. Their structures were elucidated on the basis of
      spectroscopic methods, including 2D NMR techniques. Compounds 2, 4, 5, and 8
      showed moderate neuraminidase inhibitory activity with IC(50) values ranging from
      4.15 to 9.16 uM.

PMID- 21969117
TI  - Clerodane diterpenoids from Tinospora sagittata (Oliv.) Gagnep.
AB  - Three new clerodane diterpene glycosides, tinospinosides A (1), B (2), and C (3)
      were isolated from the roots of Tinospora sagittata (Oliv.) Gagnep. Their
      structures were determined to be (2 S,4a R,6a R,9 R,10a S,10b S)-2-(3-furanyl)-9
      ( beta-D-glucopyranosyloxy)-1,4,4a,5,6,6a,9,10,10a,10b-decahydro-6a,10b-dimethyl
      4-oxo-2H-naphtho[2,1-c]pyran-7-carboxylic acid methyl ester (1), (2 S,4a S,6a R,9
      R,10a R,10b S)-2-(3-furanyl)-9-( beta-D-glucopyranosyloxy)
      1,4,4a,5,6,6a,9,10,10a,10b-decahydro-4a-hydroxyl-6a,10b-dimethyl-4-oxo-2H
      naphtho[2,1-c]pyran-7-carboxylic acid methyl ester (2) and (2 S,4a R,6a R,9 R,10a
      R,10b S)-2-(3-furanyl)-9-( beta-D-glucopyranosyloxy)-1,4,4a,5,6,6a,9,10,10a,10b
      decahydro-4a-hydroxyl-6a,10b-dimethyl-4-oxo-2H-naphtho[2,1-c]pyran-7-carboxylic
      acid methyl ester (3), by various spectroscopic analyses, chemical reactions, and
      computer-assisted calculations. The inhibitory activities of NO production by
      these compounds and their chemical derivatives in lipopolysaccharide and TNF
      gamma-activated macrophage-like cell line J774.1 were tested. Tinospin A, 12- EPI
      tinospin A, tinospinoside B, and tinospinoside C showed inhibitory activities of
      NO production with the IC(50) values of 162, 182, 290, and 218 uM, respectively.

PMID- 21969118
TI  - Evaluation of confidence limit estimates of cluster analysis on molecular marker
      data.
AB  - BACKGROUND: Diversity studies employ cluster analysis as a statistical tool,
      whereby relationships between individuals are shown in a dendrogram, mostly
      accompanied by bootstrap support for merging branches to indicate confidence
      limits. The objective of this study was to evaluate the reliability of the
      currently applied method of obtaining confidence limit estimates in cluster
      analysis and to propose an improved alternative bootstrap method. RESULTS: It was
      illustrated via a simulation study that conventional bootstrap support for
      cluster analysis was affected by the sample size. The reliability of merging
      branches decreased with increasing number of individuals in the sample. Unlike
      the current bootstrap support for cluster analysis, the proposed method provides
      confidence intervals for the similarity coefficients between individuals. To
      facilitate the interpretation of similarity coefficients and confidence
      intervals, alternative graphical presentations are proposed for both 'similarity
      coefficients' and 'confidence interval range'. CONCLUSION: The proposed bootstrap
      method is not affected by the number of individuals in the sample.

PMID- 21969119
TI  - The immunohistochemical characterization of sarcomatoid malignant mesothelioma of
      the pleura.
AB  - The immunohistochemical characteristics of epithelioid malignant mesothelioma are
      well described. However, immunohistochemical analyses of sarcomatoid
      mesothelioma, the less common type, are limited and its distinction from other
      tumors of the chest wall, lung and pleura is often problematic. We evaluated 24
      patients with pleural sarcomatoid mesothelioma who had surgery (12 extrapleural
      pneumonectomies, 9 pleurectomies and 3 large biopsies) between 1989 and 2005.
      Clinicopathologic features and demographic data were recorded. We describe
      immunohistochemical results for 10 antibodies: AE1/AE3, CAM5.2 and MNF-116
      keratins, calretinin, WT-1 protein, bcl-2, CD34, desmin, D2-40 and podoplanin.
      The patients were 23 men and one woman with a median age at diagnosis of 64.7
      years (range 47 to 76). Tumor cells were positive for the keratin proteins
      AE1/AE3 in 18/24 cases, CAM 5.2 in 23/24 cases and MNF-116 in 21/21 cases.
      Calretinin was positive in 6/24 cases, WT-1 (nuclear) in 8/24 cases, bcl-2 in
      0/24 cases, CD34 in 0/24 cases, desmin in 0/24 cases, D2-40 in 24/24 cases and
      podoplanin in 24/24 cases. This panel of antibodies may be helpful in
      establishing a pathologic diagnosis of sarcomatoid mesothelioma. In our study, D2
      40 and podoplanin are highly sensitive immunohistochemical markers for
      sarcomatoid mesothelioma. Additional studies are required to define their role in
      the differential diagnosis of other spindle cell tumors.

PMID- 21969120
TI  - A radical cyclization approach to the formal total syntheses of platencin.
AB  - Two different strategies leading to formal total syntheses of platencin are
      described. The first strategy involving Claisen rearrangement and radical
      cyclization provides a rapid access to the core structure of platencin, and also
      use minimum protective-group operations. The second strategy, a protecting group
      free route, utilizes a 6-exo-trig radical cyclization and aldol condensation as
      key steps leading to the formal synthesis of platencin.

PMID- 21969121
TI  - Xanthium strumarium: a weed host of components of begomovirus-betasatellite
      complexes affecting crops.
AB  - Xanthium strumarium is a common weed that often shows symptoms typical of
      begomovirus infection, such as leaf curling and vein thickening. The virus
      complex isolated from the weed consisted of two begomoviruses along with a
      betasatellite and an alphasatellite. The first begomovirus was shown to be an
      isolate of Cotton leaf curl Burewala virus, a new recombinant begomovirus species
      that is associated with resistance breaking in previously resistant cotton
      varieties in Pakistan, whereas the second was shown to be an isolate of Tomato
      leaf curl Gujarat virus (ToLCGV), a begomovirus previously reported to be
      bipartite. However, there was no evidence for the presence of the second genomic
      component, DNA B, of ToLCGV in X. strumarium. The betasatellite was shown to be
      an isolate of Tomato yellow leaf curl Thailand betasatellite, the first time this
      satellite has been identified in Pakistan. The alphasatellite associated with
      infection of X. strumarium was shown to be a species recently identified in
      potato and various weeds; Potato leaf curl alphasatellite. Although each
      component has been identified previously, this is the first time they have been
      identified in a single host. These findings reinforce the hypothesis that weeds
      are reservoirs of crop-infecting begomoviruses that may contribute to virus
      diversity by virtue of harboring multiple viruses and virus associated
      components, which may lead to interspecific recombination and component exchange.

PMID- 21969122
TI  - DNA methyl transferase 1: regulatory mechanisms and implications in health and
      disease.
AB  - DNA methylation serves as the principal form of post-replicative epigenetic
      modification. It is intricately involved in gene regulation and silencing in
      eukaryotic cells, making significant contributions to cell phenotype. Much of it
      is mitotically inherited; some is passed on from one filial generation to the
      next. Establishment and maintenance of DNA methylation patterns in mammals is
      governed by three catalytically active DNA methyltransferases - DNMT3a, DNMT3b
      and DNMT1. While the first two are responsible mainly for de novo methylation,
      DNMT1 maintains the methylation patterns by preferentially catalyzing S-adenosyl
      methionine-dependant transfer of a methyl group to cytosine at hemimethylated CpG
      sites generated as a result of semi-conservative DNA replication. DNMT1 contains
      numerous regulatory domains that fine-tune associated catalytic activities,
      deregulation of which is observed in several diseases including cancer. In this
      minireview, we analyze the regulatory mechanisms of various sub-domains of DNMT1
      protein and briefly discuss its pathophysiological and pharmacological
      implications. A better understanding of DNMT1 function and structure will likely
      reveal new applications in the treatment of associated diseases.

PMID- 21969123
TI  - Manipulation of nicotinic acetylcholine receptors differentially affects
      behavioral inhibition in human subjects with and without disordered baseline
      impulsivity.
AB  - RATIONALE: Evidence for a relationship between cigarette smoking and attention
      deficit/hyperactivity disorder (ADHD) has prompted investigations into nicotinic
      treatments for this disorder. Impulsivity is a hallmark of ADHD and is measured
      in the laboratory as behavioral inhibition (BI) using the stop signal task (SST).
      Acute nicotine improves SST performance in adolescents and young adults who have
      both ADHD and impaired baseline SST performance, raising questions about the role
      of nicotinic acetylcholine receptor function in BI. The specificity of this
      effect to those with ADHD, the component processes of the SST affected by
      nicotine, and the effects of nicotinic antagonism are yet unknown. OBJECTIVES:
      This study investigated the effects of both a nicotinic receptor agonist and
      antagonist on the SST and choice reaction time task (CRT) in highly impulsive
      (HI) and control (CTRL) subjects. METHODS: This was a within-subjects, double
      blind study of: 7 mg transdermal nicotine, 20 mg oral mecamylamine, and placebo.
      Subjects were recruited into HI (n = 11) and CTRL (n = 14) groups based on both
      SST and clinical criteria. RESULTS: BI was significantly improved by nicotine
      compared with placebo in the HI group and impaired by mecamylamine in the CTRL
      group. Go signal reaction time on the SST was improved by nicotine compared with
      placebo in the CTRL group and was unchanged in both groups on the CRT.
      CONCLUSIONS: These findings demonstrate nicotinic modulation of BI in subjects
      with both normal and disordered baseline performance. The effects on BI are
      consistent with cholinergic enhancement of signal detection processes and/or
      modulation of noradrenaline by nicotine.

PMID- 21969124
TI  - Galanin negatively modulates opiate withdrawal via galanin receptor 1.
AB  - RATIONALE: The neuropeptide galanin has been shown to modulate opiate dependence
      and withdrawal. These effects could be mediated via activation of one or more of
      the three distinct G protein-coupled receptors, namely galanin receptors 1
      (GalR1), 2 (GalR2), and 3 (GalR3). OBJECTIVES: In this study, we used several
      transgenic mouse lines to further define the mechanisms underlying the role
      played by galanin and its receptors in the modulation of morphine dependence.
      First, transgenic mice expressing beta-galactosidase under the control of the
      galanin promoter were used to assess the regulation of galanin expression in
      response to chronic morphine administration and withdrawal. Next, the behavioral
      responses to chronic morphine administration and withdrawal were tested in mice
      that over-express galanin, lack the GalR1 gene, or lack the GalR2 gene. METHODS:
      Transgenic and matched wild-type mice were given increasing doses of morphine
      followed by precipitation of withdrawal by naloxone and behavioral responses to
      withdrawal were assessed. RESULTS: Both morphine administration and withdrawal
      increased galanin gene transcription in the locus coeruleus (LC). Increasing
      galanin levels in the brain reduced signs of opiate withdrawal. Mice lacking
      GalR1 undergo more severe opiate withdrawal, whereas mice lacking GalR2 show no
      significant difference in withdrawal signs, compare with matched wild-type
      controls. CONCLUSIONS: Opiate administration and withdrawal increase galanin
      expression in the LC. Galanin opposes the actions of morphine which leads to
      opiate dependence and withdrawal, an effect that is mediated via GalR1.

PMID- 21969125
TI  - Stimulation of the intra-cardiac vagal nerves innervating the AV-node to control
      ventricular rate during AF: specificity, parameter optimization and chronic use
      up to 3 months.
AB  - BACKGROUND: Stimulation of the intra-cardiac vagal nerves innervating the AV-node
      (AVNS) is a promising approach to slow down ventricular rate (VR) during atrial
      fibrillation (AF). Our purpose was to demonstrate that effects on R-R-interval
      during stable AF can be maintained for several months once optimized and that
      AVNS affects specifically the nerves innervating the AV-node. METHODS: Our study
      included both an acute and chronic phase. Fifteen goats were implanted with a
      pacemaker connected to an atrial and ventricular lead and a neurostimulator
      connected to an atrial lead placed at a certain septal site, to induce an AV
      prolongation. In the chronic experiments (n = 9), after assessment of optimal
      AVNS parameters, the effect of continuous AVNS on VR was studied during stable AF
      for up to 3 months. The mechanism of AVNS was studied using atropine and esmolol.
      Next, the effects of AVNS during the atrial refractory period on
      electrophysiological and hemodynamic parameters were investigated acutely (n =
      7). RESULTS: The maximal effect was found at a stimulation frequency of 40 Hz,
      and increased with increasing pulse width (at lower voltages) and increasing
      voltage. After 0, 1, and 3 months of AVNS during stable AF, AVNS decreased
      average VR, respectively, 55% (n = 9), 48% (n = 8), and 28% (n = 6). The AVNS
      effect appeared to be dominantly parasympathetic. AVNS did not influence (1) the
      sinus node, (2) the refractory period of the atrial, ventricular tissue, and His
      and (3) hemodynamic parameters. CONCLUSION: AVNS is efficient in reducing
      ventricular rate for at least 3 months using optimized parameters and
      specifically affects the parasympathetic nerves innervating the AV-node.

PMID- 21969127
TI  - From zigzag to armchair: the energetic stability, electronic and magnetic
      properties of chiral graphene nanoribbons with hydrogen-terminated edges.
AB  - The energetic stability, electronic and magnetic properties of chiral graphene
      nanoribbons (GNRs) with hydrogen-terminated edges are investigated using density
      functional theory. Our calculations show that the percentage of carbon atoms at
      the zigzag sites (P(z)) is the key factor determining the electronic and magnetic
      properties of chiral GNRs. Within the local spin density approximation, chiral
      GNRs with P(z) >= 50% have a semiconducting antiferromagnetic ground state.
      Otherwise, chiral GNRs are spin degenerate semiconductors. Thus, the critical
      chiral angle for the occurrence of spin polarization is determined to be 13.9
      degrees . In contrast to the antiferromagnetic state that is independent of the
      width of GNRs investigated, size effects occur for the ferromagnetic metastable
      state. These findings are helpful for the design of GNR-based spintronic devices.

PMID- 21969126
TI  - Molecular aspects of renal cell carcinoma: a review.
AB  - Renal cell carcinoma (RCC) is a disease in which cancer cells form in the tubules
      of the kidney. RCC, the incidence of which is increasing annually, represents
      five percent of adult epithelial cancers. Clear cell carcinoma represents the
      most frequent histological subtype. RCC is characterized by a lack of early
      warning signs, diverse clinical manifestations. Incidentally detected tumors in
      asymptomatic individuals have been steadily increasing owing to the increased
      usage of various imaging technologies. Currently there are no recommendations for
      screening to detect and make an early diagnosis of renal cancer. But in recent
      years, the discovery of new molecular and cytogenetic markers has led to the
      recognition and classification of several novel subtypes of RCC, and the
      introduction of molecular-targeted therapy for advanced-stage RCC. We performed a
      literature review using PubMed and discuss current knowledge of epidemiology,
      pathophysiology, evaluation, treatment, and future research directions of RCC.

PMID- 21969128
TI  - Prevalence of Intestinal Parasites among Pupils in Rural North Eastern, Nigeria.
AB  - BACKGROUND: The study determined the prevalence of intestinal parasitism among
      pupils in rural schools (Almajiris) in Konduga local Government Area of Borno
      state.  MATERIALS AND METHODS: A total of 257 stool specimens were collected at
      random among pupils (Almajiris) in rural quranic schools; the stools were
      processed and examined both macroscopically and microscopically by concentration
      techniques.  RESULTS: The prevalence of intestinal parasitism among the Almajiris
      was 80.9%. The highest prevalence rate was 97.8% while the least prevalence was
      67.4%. The 6-8 years age group had the highest prevalence of 85.7% while the
      least prevalence of 77.7% in the 13-16years age bracket. Ascaris lumbricoides had
      the highest prevalence of (19.1%) while Trichuris trichiura had the least
      prevalence of (3.5%). Thirteen pupils in the 5-8 years had multiple parasites;
      multiple parasitism also occurred in 22 pupils aged 9-12 years and in 11 pupils
      aged 13-16 years.  CONCLUSION: There is a high prevalence rate of intestinal
      parasites with attendant risk of intestinal obstruction among the Almajiris in
      rural north eastern Nigeria.

PMID- 21969129
TI  - Tyrosine kinase expression profile in clear cell renal cell carcinoma.
AB  - PURPOSE: To profile different tyrosine kinase (TK) expression patterns in clear
      cell renal carcinoma (ccRCC). METHODS: We analysed mRNA expression levels of 89
      receptor and non-receptor TK in corresponding cancer and normal renal tissue from
      5 patients with ccRCC using the TaqMan Low-Density Array technology. In order to
      confirm aberrant TK expressions, a subsequent analysis of 25 ccRCC and
      corresponding normal renal tissues was performed, applying quantitative real-time
      PCR. To confirm mRNA expression levels on protein level, we studied ERBB4 and HCK
      using immunohistochemistry. RESULTS: A total of 12 TK were significantly
      upregulated in ccRCC (ABL2, FLT1, BTK, HCK, JAK3, CSF1R, MET, JAK1, MATK, PTPRC,
      FYN and CSK), coherently 7 TK demonstrated a down-regulation (ERBB4, PDGFRA,
      NRTK3, SYK, ERBB2, FGFR3 and PTK7). These findings were validated by the
      utilization of RT-PCR for ABL2, FLT1 BTK, HCK, JAK3, CSF1R, MET, JAK1, MATK and
      vice versa for ERBB4 and PDGFRA. Immunohistochemistry revealed ERBB4 expression
      to be significantly lower in ccRCC in comparison to papillary RCC, chromophobe
      RCC, renal oncocytoma and normal renal tissue (P < 0.001). HCK protein expression
      was reduced in ccRCC in contrast to papillary RCC (P < 0.001) or oncocytoma (P =
      0.023), but similar to chromphobe RCC (P = 0.470), sarcomatoid RCC (P = 0.754)
      and normal renal tissue (P = 0.083). Neither ERBB4 nor HCK were correlated (P >
      0.05) with clinical-pathological parameters. CONCLUSION: TK constitute valuable
      targets for pharmaceutical anti-cancer therapy. ERBB4 and HCK depict
      significantly lower expression levels in renal cancer tissues.

PMID- 21969130
TI  - XPA-210: a new proliferation marker determines locally advanced prostate cancer
      and is a predictor of biochemical recurrence.
AB  - PURPOSE: XPA-210 is a proliferation marker derived from Thymidine kinase-1. It is
      of clinical significance in kidney, breast, and bladder cancer. There are no data
      available for XPA-210 in prostate cancer (PC). Herein, we aim to determine the
      clinical usefulness of XPA-210 in PC. MATERIALS AND METHODS: In a retrospective
      study, cancer and benign tissue samples of 103 patients (median age 65 years,
      median PSA 9.04 ng/ml, median Gleason score 6) who underwent prostatectomy were
      constructed to a tissue micro array and stained for XPA-210. Semi-quantitative
      results were correlated with pathological and clinical data by Wilcoxon-Kruskall
      Wallis and linear regression analysis. Expression levels in PC were correlated
      between the time of biochemical recurrence and the time to development of
      metastasis by the Kaplan-Meier method. Multivariate analysis was done to
      correlate those with the resection status. RESULTS: Mean staining score was 0.51
      0.14 for tumor and benign tissue (P < 0.0001). Tumor staining score was
      significantly associated with Gleason score <6/>=6 (P < 0.0001) and T2/T >2 (P =
      0.0007). When dividing the tumor score by the mean value, higher expression of
      XPA-210 was associated with a shorter time to biochemical recurrence (P = 0.003)
      and time to development of metastasis (P = 0.0061). Tumor staining (P = 0.0371)
      was an independent prognostic factor for biochemical relapse regardless of
      resection status. CONCLUSIONS: XPA-210 is a new tissue-based prognostic marker
      for prostate cancer histopathology. It reliably differentiates tumor and normal
      prostatic tissue predicting biochemical relapse and onset of metastatic disease.
      XPA-210 might be clinically useful for individual decision-making in PC
      treatment.

PMID- 21969131
TI  - CD133 immunohistochemical expression predicts progression and cancer-related
      death in renal cell carcinoma.
AB  - PURPOSE: To evaluate the prognostic impact of the histological expression of
      CD133 in renal cell carcinoma (RCC). METHODS: From 1992 to 2009, 142 consecutive
      patients underwent radical nephrectomy or partial nephrectomy for RCC. All cases
      were reviewed by a single pathologist and then subjected to analysis of the
      immunohistochemical expression of CD133 using tissue microarray. Several clinical
      and pathological variables were also evaluated. RESULTS: The median postoperative
      follow-up was 44 months. Of the 142 immunostained RCC specimens, 77 (54%) showed
      low and 65 (46%) high expression of CD133. Expression of CD133 was associated
      with clinical stage (P = 0.05), lymph node involvement (P = 0.03), metastatic
      disease (P = 0.02) and MVI (P = 0.03). Among other variables, clinical stage,
      necrosis and metastasis were associated with disease-specific survival (DSS) and
      progression-free survival (PFS) on univariate analysis. The 5-year PFS rates in
      patients who provided specimens with high and low expression of CD133 were 83 and
      66%, respectively (P = 0.01). It was observed that the 5-year DSS for patients
      who provided specimens with high and low expression of CD133 was 90 and 71%,
      respectively (P = 0.003). Multivariate survival analysis showed that patients in
      the CD133 low-expression group had a higher probability of disease progression
      (HR 3.4, P = 0.02) and a higher probability of death from cancer (HR 2.4, P =
      0.01). CONCLUSIONS: Immunohistochemical expression of CD133 had an impact on
      survival in patients with RCC, which shows that CD133 might be a useful tool for
      risk stratification. Low expression of this marker remained as an independent
      predictor of poor DSS and PFS.

PMID- 21969132
TI  - Individual receptor profiling as a novel tool to support diagnosis of bladder
      pain syndrome/interstitial cystitis (BPS/IC).
AB  - PURPOSE: Dysregulation of neurotransmitter receptors may contribute to bladder
      overactivity (OAB) symptoms. To address the question whether specific receptor
      expression patterns are associated with bladder pain syndrome/interstitial
      cystitis (BPS/IC), we examined the expression of muscarinic, purinergic and
      histamine receptors in the detrusor. METHODS: Detrusor receptor expression was
      investigated in bladder biopsies of female BPS/IC patients (n = 44; age 60.64 +/-
      13.78, mean +/- SD) and carcinoma patients (n = 11; age 58.91 +/- 12.72)
      undergoing cystectomy. Protein expression of muscarinic (M2, M3), purinergic
      (P2X1-3) and histamine receptors (H1, H2) was analysed by confocal
      immunofluorescence, and gene expression was quantified by real-time polymerase
      chain reaction (qPCR). RESULTS: M2, P2X1, P2X2 and H1 receptor immunoreactivity (
      IR) was significantly enhanced in BPS/IC compared to the control group, while
      there was no difference for M3-, P2X3- and H2-IR. We calculated a score, which
      separated BPS/IC from control patients with an AUC of 89.46%, showing 84.09%
      sensitivity and 90.91% specificity. Patients had a 9.25 times enhanced calculated
      risk for BPS/IC. In addition, two patient subgroups (M2 > M3 and M3 > M2) were
      observed, which differed in associated purinergic and histamine receptor
      expression. CONCLUSIONS: M2, P2X1, P2X2 and H1 were significantly upregulated in
      BPS/IC patients, and H2 was occasionally highly overexpressed. There was no
      significant correlation between receptor protein and gene expression, implying
      posttranslational mechanisms being responsible for the altered receptor
      expressions. On the basis of individual receptor profiles, upregulated receptors
      could be targeted by monotherapy or combination therapy with already approved
      receptor inhibitors, thereby promoting tailored therapy for patients suffering
      from BPS/IC-like symptoms.

PMID- 21969133
TI  - Breast cancer statistics, 2011.
AB  - In this article, the American Cancer Society provides an overview of female
      breast cancer statistics in the United States, including trends in incidence,
      mortality, survival, and screening. Approximately 230,480 new cases of invasive
      breast cancer and 39,520 breast cancer deaths are expected to occur among US
      women in 2011. Breast cancer incidence rates were stable among all racial/ethnic
      groups from 2004 to 2008. Breast cancer death rates have been declining since the
      early 1990s for all women except American Indians/Alaska Natives, among whom
      rates have remained stable. Disparities in breast cancer death rates are evident
      by state, socioeconomic status, and race/ethnicity. While significant declines in
      mortality rates were observed for 36 states and the District of Columbia over the
      past 10 years, rates for 14 states remained level. Analyses by county-level
      poverty rates showed that the decrease in mortality rates began later and was
      slower among women residing in poor areas. As a result, the highest breast cancer
      death rates shifted from the affluent areas to the poor areas in the early 1990s.
      Screening rates continue to be lower in poor women compared with non-poor women,
      despite much progress in increasing mammography utilization. In 2008, 51.4% of
      poor women had undergone a screening mammogram in the past 2 years compared with
      72.8% of non-poor women. Encouraging patients aged 40 years and older to have
      annual mammography and a clinical breast examination is the single most important
      step that clinicians can take to reduce suffering and death from breast cancer.
      Clinicians should also ensure that patients at high risk of breast cancer are
      identified and offered appropriate screening and follow-up. Continued progress in
      the control of breast cancer will require sustained and increased efforts to
      provide high-quality screening, diagnosis, and treatment to all segments of the
      population.

PMID- 21969135
TI  - Capuchin monkeys (Cebus nigritus) use spatial and visual information during
      within-patch foraging.
AB  - Foraging in large-scale (navigation between patches), small-scale (choice of
      within-patch feeding sites), and micro-scale (close inspection of food items)
      space presents variable cognitive challenges. The reliability and usefulness of
      spatial memory and perceptual cues during food search in a forest environment
      vary among these spatial scales. This research applied an experimental field
      design to test the ability of a free-ranging group composed of eight black-horned
      capuchin monkeys, Cebus nigritus, inhabiting a forest fragment in Porto Alegre,
      State of Rio Grande do Sul, Brazil, to use food-associated spatial, visual,
      olfactory, and quantitative (amount of food) cues during small-scale foraging
      decisions. The experimental design involved the establishment of a feeding
      station composed of eight feeding platforms distributed in a circular
      arrangement. A series of six experiments, each lasting 20 days, was conducted
      from March to August 2005. Two feeding platforms in each experimental session
      contained a food reward (real banana), whereas the remaining six platforms
      contained either a sham banana or an inaccessible real banana. Data on capuchin
      monkey foraging behavior at the feeding stations were collected by the "all
      occurrences" sampling method. The performance of the capuchins in the experiments
      was analyzed based on the first two platforms inspected in each session. The
      study group inspected feeding platforms in 571 occasions during 113 sessions.
      Capuchins used visual cues and spatial information (and adopted a win-return
      strategy) for finding the platforms baited with real bananas and showed weak
      evidence of the integration of spatial and quantitative cues, but failed to show
      evidence of using olfactory cues. In addition, individual differences in social
      rank and foraging behavior affected opportunities for learning and the
      performance in the cognitive tasks.

PMID- 21969134
TI  - Spatial dependence of alveolar angiogenesis in post-pneumonectomy lung growth.
AB  - Growth of the remaining lung after pneumonectomy has been observed in many
      mammalian species; nonetheless, the pattern and morphology of alveolar
      angiogenesis during compensatory growth is unknown. Here, we investigated
      alveolar angiogenesis in a murine model of post-pneumonectomy lung growth. As
      expected, the volume and weight of the remaining lung returned to near-baseline
      levels within 21 days of pneumonectomy. The percentage increase in lobar weight
      was greatest in the cardiac lobe (P < 0.001). Cell cycle flow cytometry
      demonstrated a peak of lung cell proliferation (12.02 +/- 1.48%) 6 days after
      pneumonectomy. Spatial autocorrelation analysis of the cardiac lobe demonstrated
      clustering of similar vascular densities (positive autocorrelation) that
      consistently mapped to subpleural regions of the cardiac lobe.
      Immunohistochemical staining demonstrated increased cell density and enhanced
      expression of angiogenesis-related factors VEGFA, and GLUT1 in these subpleural
      regions. Corrosion casting and scanning electron microscopy 3-6 days after
      pneumonectomy demonstrated subpleural vessels with angiogenic sprouts. The
      monopodial sprouts appeared to be randomly oriented along the vessel axis with
      interbranch distances of 11.4 +/- 4.8 MUm in the regions of active angiogenesis.
      Also present within the regions of increased vascular density were frequent
      "holes" or "pillars" consistent with active intussusceptive angiogenesis. The
      mean pillar diameter was 4.2 +/- 3.8 MUm, and the pillars were observed in all
      regions of active angiogenesis. These findings indicate that the process of
      alveolar construction involves discrete regions of regenerative growth,
      particularly in the subpleural regions of the cardiac lobe, characterized by both
      sprouting and intussusceptive angiogenesis.

PMID- 21969136
TI  - What is known about parents' treatment decisions? A narrative review of pediatric
      decision making.
AB  - BACKGROUND: With the increasing complexity of decisions in pediatric medicine,
      there is a growing need to understand the pediatric decision-making process.
      OBJECTIVE: To conduct a narrative review of the current research on parent
      decision making about pediatric treatments and identify areas in need of further
      investigation. METHODS: Articles presenting original research on parent decision
      making were identified from MEDLINE (1966-6/2011), using the terms "decision
      making," "parent," and "child." We included papers focused on treatment decisions
      but excluded those focused on information disclosure to children, vaccination,
      and research participation decisions. RESULTS: We found 55 papers describing 52
      distinct studies, the majority being descriptive, qualitative studies of the
      decision-making process, with very limited assessment of decision outcomes.
      Although parents' preferences for degree of participation in pediatric decision
      making vary, most are interested in sharing the decision with the provider. In
      addition to the provider, parents are influenced in their decision making by
      changes in their child's health status, other community members, prior knowledge,
      and personal factors, such as emotions and faith. Parents struggle to balance
      these influences as well as to know when to include their child in decision
      making. CONCLUSIONS: Current research demonstrates a diversity of influences on
      parent decision making and parent decision preferences; however, little is known
      about decision outcomes or interventions to improve outcomes. Further
      investigation, using prospective methods, is needed in order to understand how to
      support parents through the difficult treatment decisions.

PMID- 21969138
TI  - Klotho is silenced through promoter hypermethylation in gastric cancer.
AB  - As one of major epigenetic changes to inactivate tumor suppressor genes in human
      carcinogenesis, promoter hypermethylation was proposed as a marker to define
      novel tumor suppressor genes and predict the prognosis of cancer patients. In the
      present study, we found KL (klotho) as a novel tumor suppressor gene silenced
      through promoter hypermethylation in gastric cancer, the second leading cause of
      cancer death worldwide. KL expression was downregulated in primary gastric
      carcinoma tissues (n=22, p<0.05) and all of gastric cancer cells lines examined.
      Ectopic expression of KL inhibited the growth of gastric cancer cells partially
      through the induction of apoptosis, demonstrating a tumor suppressive role of KL
      in gastric cancer. Demethylation with 5-aza-2'-deoxycytidine (Aza) increased KL
      expression and KL promoter was hypermethylated in gastric cancer cell lines as
      well as some of primary gastric carcinoma tissues (47/99) but none of normal
      gastric tissues. Importantly, promoter methylation of KL was significantly
      associated with the poor outcome of gastric cancer patients (p=0.025, Log-rank
      test), highlighting the relevance of epigenetic inactivation of KL in gastric
      carcinogenesis. As a summary, we found that KL is a novel tumor suppressor gene
      epigenetically inactivated in gastric cancer and promoter methylation of KL could
      be used to predict the prognosis of gastric cancer patients.

PMID- 21969139
TI  - [Awards in psychosomatic medicine--how much evaluation and support is needed in
      psychosomatic research].

PMID- 21969137
TI  - Extracellular ATP induces fast and transient non-selective cationic currents and
      cytosolic Ca2+ changes in human umbilical artery smooth muscle cells.
AB  - Ionotropic purinergic receptors (P2X) are expressed in endothelial and smooth
      muscle cells of blood vessels. ATP acting on smooth muscle P2X receptors is able
      to induce vasoconstriction in different kind of vessels. However, to our
      knowledge, there are no reports that directly show the activity of these
      purinergic receptors in native human vascular smooth muscle cells. In this work,
      we describe for the first time an ATP-induced current in freshly isolated human
      umbilical artery (HUA) smooth muscle cells. The current was measured by patch
      clamp technique in whole-cell condition on cells clamped at -50 mV. At 100 MUM of
      ATP the current showed a rapid activation and desensitization, and was carried by
      both Na(+) and Ca(2+). The current was completely blocked by suramin (300 MUM)
      and partially blocked by 100 MUM of Zn(2+) without affecting the kinetic of
      desensitization. All these properties suggest that the ATP-induced ionic currents
      are mediated through P2X(1)-like receptors. Moreover, we show that ATP
      transiently increased cytosolic Ca(2+) in "in situ" smooth muscle cells of intact
      HUA segments and that this response is dependent of extracellular and
      intracellular Ca(2+). These data expand the knowledge of purinergic receptors
      properties in vascular smooth muscle cells and the probable role of ATP as a
      paracrine modulator of contractile tone in a human artery which is fundamental
      for feto-placental blood flow.

PMID- 21969140
TI  - [Evaluation of an inpatient parent-child-rehabilitation program: symptoms of
      psychological distress and quality of life].
AB  - OBJECTIVE: To evaluate the short- and medium-term effectiveness of an inpatient
      parent-child rehabilitation program in reducing symptoms of psychological
      distress and in increasing the quality of life of parents and children. METHODS:
      Psychological problems and quality of life of parents and children were assessed
      4 weeks before admission, at admission and discharge from the program, and 3
      months post discharge using standardized questionnaires. The sample consisted of
      256 parents, parent ratings of 397 children and self reports of 124 school-aged
      children. RESULTS: Compared to the waiting period prior to admission significant
      decreases in psychological problems as well as improvements in quality of life
      were found for both, parents and children. These effects proved to be stable over
      the follow-up period. CONCLUSIONS: Inpatient parent-child rehabilitation programs
      are effective in improving the psychological well-being and quality of life of
      parents and children.

PMID- 21969141
TI  - [Psychosocial care of children with a parent having cancer--an appraisal of
      specific care services in Germany].
AB  - Children of a parent having cancer are at greater risk to develop mental health
      problems. Aim is to investigate specific psychosocial care for children having a
      parent with cancer, as well as to characterize and assess utilization and needs
      of affected minor children. Employees of institutions in Germany supplying
      psychosocial care to families with a parent having cancer were surveyed, using a
      semi-structured interview (n = 29). Specific psychosocial care for affected
      children is limited and heterogeneous in Germany. Regarding different distress
      stages of those families, the situation could be interpreted as eligible.
      However, this primarily reflects the low quality assurance of care. Results
      suggest that in addition to preventive care needs of children having a parent
      with cancer, increased needs exist in specific risk constellations, like in
      single parent families.

PMID- 21969142
TI  - [What sample size is needed to calculate complex regression models?].

PMID- 21969143
TI  - [Results of clinical attachment research of significance for psychotherapy].

PMID- 21969144
TI  - [Awards in psychosomatic medicine].

PMID- 21969145
TI  - Global phosphorus scarcity: identifying synergies for a sustainable future.
AB  - Global food production is dependent on constant inputs of phosphorus. In the
      current system this phosphorus is not predominantly derived from organic recycled
      waste, but to a large degree from phosphate-rock based mineral fertilisers.
      However, phosphate rock is a finite resource that cannot be manufactured. Our
      dependency therefore needs to be addressed from a sustainability perspective in
      order to ensure global food supplies for a growing global population. The
      situation is made more urgent by predictions that, for example, the consumption
      of resource intensive foods and the demand for biomass energy will increase. The
      scientific and societal debate has so far been focussed on the exact timing of
      peak phosphorus and on when the total depletion of the global reserves will
      occur. Even though the timing of these events is important, all dimensions of
      phosphorus scarcity need to be addressed in a manner which acknowledges linkages
      to other sustainable development challenges and which takes into consideration
      the synergies between different sustainability measures. Many sustainable
      phosphorus measures have positive impacts on other challenges; for example,
      shifting global diets to more plant-based foods would not only reduce global
      phosphorus consumption, but also reduce greenhouse gas emissions, reduce nitrogen
      fertiliser demand and reduce water consumption.

PMID- 21969147
TI  - Assessing intraoperative blood flow in cardiovascular surgery.
AB  - Off-pump coronary arterial bypass grafting and new surgical apparatus and
      techniques have decreased the mortality rate associated with this procedure to
      approximately 1.5%. If we could detect problems in the constructed coronary
      anastomoses by an alternative imaging system to coronary angiography during
      surgery, decisions to revise the surgical procedure could be made without
      hesitation. Meanwhile, the intraoperative direct evaluation of intestinal blood
      flow during abdominal aortic aneurysmal surgery is required to prevent ischemic
      colitis, which is a devastating complication. Indocyanine green (ICG) has
      recently improved ophthalmic angiography and the navigation systems of
      oncological surgery. The fluorescence illumination of ICG with a near-infrared
      light is captured on camera. In coronary arterial surgery, the ICG imaging system
      is also becoming increasingly useful. A new ICG imaging system, the HyperEye
      Medical System (HEMS), provides a clear view of the blood flow and ischemic area
      with color visualization. Furthermore, its combination with a quantitative blood
      flow assessment tool such as transit time flow measurement could improve the
      accuracy of intraoperative examination. In this review, we evaluate the current
      strategies of assessing blood flow intraoperatively with an ICG imaging system in
      cardiovascular surgery.

PMID- 21969146
TI  - Functions of noncoding RNAs in neural development and neurological diseases.
AB  - The development of the central nervous system (CNS) relies on precisely
      orchestrated gene expression regulation. Dysregulation of both genetic and
      environmental factors can affect proper CNS development and results in
      neurological diseases. Recent studies have shown that similar to protein coding
      genes, noncoding RNA molecules have a significant impact on normal CNS
      development and on causes and progression of human neurological disorders. In
      this review, we have highlighted discoveries of functions of noncoding RNAs, in
      particular microRNAs and long noncoding RNAs, in neural development and
      neurological diseases. Emerging evidence has shown that microRNAs play an
      essential role in many aspects of neural development, such as proliferation of
      neural stem cells and progenitors, neuronal differentiation, maturation, and
      synaptogenesis. Misregulation of microRNAs is associated with some mental
      disorders and neurodegeneration diseases. In addition, long noncoding RNAs are
      found to play a role in neural development by regulating the expression of
      protein coding genes. Therefore, examining noncoding RNA-mediated gene
      regulations has revealed novel mechanisms of neural development and provided new
      insights into the etiology of human neurological diseases.

PMID- 21969148
TI  - Implications of portal vein thrombosis after splenectomy for patients with
      idiopathic portal hypertension.
AB  - PURPOSE: Idiopathic portal hypertension (IPH) is considered to be closely related
      to portal vein thrombosis (PVT). The aim of this study was to clarify the
      incidence, clinical characteristics, and outcomes of PVT in patients with IPH
      after splenectomy. METHODS: We investigated the rates, clinical characteristics,
      and outcomes of PVT in 18 patients who underwent splenectomy for IPH, during a
      mean follow-up period of 152 +/- 83 months. RESULTS: Seven of the 18 patients
      (39%) experienced gastrointestinal bleeding, which was from the varices in 4.
      Eight patients (44%) had PVT, and the mean interval until its detection after
      splenectomy was 22 +/- 41 months. The cumulative gastrointestinal bleeding rates
      5, 10, and 15 years after surgery were 24%, 31%, and 41%, respectively. The
      cumulative survival rates 5, 10, and 15 years after surgery were 94%, 74%, and
      65%, respectively. There were no significant differences in the cumulative
      gastrointestinal bleeding and survival rates between patients with and those
      without PVT. CONCLUSION: Despite the high incidence of PVT in IPH patients
      postsplenectomy, it may not be related to their gastrointestinal bleeding or
      prognosis.

PMID- 21969149
TI  - Using the E-PASS scoring system to estimate the risk of emergency abdominal
      surgery in patients with acute gastrointestinal disease.
AB  - PURPOSE: The Estimation of Physiologic Ability and Surgical Stress (E-PASS)
      scoring system, which quantifies a patient's reserve and surgical stress, is used
      to predict morbidity and mortality in patients before elective gastrointestinal
      surgery. We conducted this study to clarify whether the E-PASS scoring system is
      useful for assessing the risks of emergency abdominal surgery. METHODS: The
      subjects of this retrospective study were 51 patients who underwent emergency
      gastrointestinal surgery at a public general hospital. The main outcomes were the
      E-PASS scores and the postoperative course, defined by mortality and morbidity.
      RESULTS: Postoperative complications developed in 15 of the 51 patients (29.4%).
      The E-PASS score was significantly higher in the patients with postoperative
      complications than in those without (0.61 +/- 0.31 vs 0.20 +/- 0.35,
      respectively; n = 36). The morbidity rates were significantly lower in the
      patients with a value less than 0.5 than in those with a value more than 0.5
      (17.1% and 56.3%, respectively; P < 0.01). There were 7 operative deaths among
      the 16 patients with a high score, versus none among the 9 patients with a low
      score (P < 0.01). Three patients underwent laparoscopic-assisted bowel resection
      with a good postoperative course, with scores of less than 0.5. CONCLUSIONS: The
      E-PASS scoring system is useful for surgical decision making and evaluating
      whether patients will tolerate emergency gastrointestinal surgery. Minimally
      invasive therapy would assist in lowering the risk of complications.

PMID- 21969150
TI  - Significance of prophylactic modified radical neck dissection for patients with
      low-risk papillary thyroid carcinoma measuring 1.1-3.0 cm: first report of a
      trial at Kuma Hospital.
AB  - PURPOSE: Papillary thyroid carcinoma (PTC) frequently metastasizes to and recurs
      in regional lymph nodes. Of the two compartments, the central compartment can be
      dissected through the same wound as the thyroidectomy, and the central node
      dissection (CND) is routinely performed in most Japanese surgical departments.
      However, the indications for prophylactic lateral compartment dissection
      (modified radical neck dissection [MND]) for low-risk PTC remain unclear. In this
      study, we investigated the indications for prophylactic MND for PTC patients with
      tumor measuring 1.1-3.0 cm without significant extrathyroid extension or distant
      metastasis. METHODS: We investigated the lymph node disease-free survival (LN
      DFS) rates of 829 patients who underwent CND and of 414 patients who underwent
      MND and CND between 2005 and 2007 at Kuma Hospital. RESULTS: The LN-DFS of these
      two groups was not significantly different. In the subset of patients with CND
      only, clinical central node metastasis (N1a) significantly predicted a worse LN
      DFS. All N1a patients recognized as showing recurrence developed such recurrence
      in the lateral compartment. Other conventional prognostic factors, such as sex
      and age, were not related to LN-DFS. CONCLUSION: Taken together, N1a patients
      with low-risk PTC measuring 1.1-3.0 cm can be considered as candidates for
      prophylactic MND.

PMID- 21969151
TI  - Concurrent chemoradiotherapy using cisplatin plus S-1, an oral fluoropyrimidine,
      followed by surgery for selected patients with stage III non-small cell lung
      cancer: a single-center feasibility study.
AB  - PURPOSE: This single-institutional study was designed to determine whether S-1,
      an oral fluoropyrimidine, plus cisplatin with concurrent radiotherapy is feasible
      as an induction treatment for locally advanced non-small cell lung cancer
      (NSCLC). METHODS: Eighteen patients were analyzed in this study from July 2005 to
      March 2008. The patients received 40 mg/m(2) S-1 orally twice per day on days 1
      through 14 and 22 through 35, and cisplatin (60 mg/m(2)) was injected
      intravenously on days 8 and 29. The patients also underwent radiotherapy, and
      received a total dose of 40 Gy in 20 fractions beginning on day 1. Surgical
      resection was performed from 3 to 6 weeks after completing the induction
      treatment. RESULTS: Nine (50%) of the 18 patients who received the induction
      treatment achieved a partial response. One patient refused to undergo surgery.
      The remaining 17 patients underwent a complete surgical resection. There were no
      deaths nor any major morbidities during the perioperative period. The recurrence
      free survival and overall survival rate at 2 years for the patients who underwent
      resection were 63.3% and 88.2%, respectively. CONCLUSION: Induction treatment
      using S-1 plus cisplatin and concurrent radiotherapy and surgical resection for
      selected patients with stage III NSCLC is a feasible and promising new treatment
      modality.

PMID- 21969152
TI  - A prospective comparative study of the efficacy of conventional Lichtenstein
      versus self-adhesive mesh repair for inguinal hernia.
AB  - PURPOSE: Lichtenstein repair has been the gold standard in inguinal hernia
      surgery. The aim of this study was to investigate the role of mesh fixation in
      terms of postsurgical chronic pain and recurrence. METHODS: Sixty patients with
      primary inguinal hernias were treated between March 2007 and December 2008.
      Thirty patients underwent conventional Lichtenstein repair while a self-adhesive
      mesh was used for the second group. The primary outcome parameters were the rate
      of recurrence and chronic pain. The operating time, postoperative pain,
      complications, and time when patients returned to work were recorded. RESULTS:
      Fifty-one patients completed the survey. Early pain scores were lower in the self
      adhesive mesh group. The main advantage of the self-adhesive mesh was the shorter
      operating time (23.70 +/- 5.57 vs 36.90 +/- 11.36, P = 0.006). Both techniques
      were almost identical in terms of long-term chronic pain (P = 0.294), and the
      rates of recurrence at the end of a median of 31 months' follow-up were
      identical. CONCLUSION: Self-adhesive mesh repair of inguinal hernias is superior
      to the conventional Lichtenstein method in terms of shorter operative time and
      less pain in the early postoperative period. The rates of chronic pain and
      recurrence are similar with the suture-fixed repairs.

PMID- 21969153
TI  - Neutrophil dysfunction in steroid-overdosed patients with ulcerative colitis:
      potential relevance of macrophage migration inhibitory factor to increased
      postoperative morbidity.
AB  - PURPOSE: We studied macrophage migration inhibitory factor (MIF)-related
      neutrophil dysfunction in patients with ulcerative colitis (UC), under conditions
      of surgical stress, focusing in particular on total preoperative steroid dosages.
      METHODS: Neutrophils were isolated from peripheral blood samples obtained from 21
      UC patients soon after radical surgery for UC. The patients were divided into two
      subgroups according to their total preoperative prednisolone dosages. The
      neutrophil phagocytosis, viable cell, and cell necrosis rates after exposure to
      Escherichia coli were evaluated by flow cytometry. The supernatant concentrations
      of mediators after exposure to E. coli were evaluated by enzyme-linked
      immunosorbent assay. RESULTS: There was a significant positive correlation
      between the levels of MIF and the total preoperative dosage of prednisolone. More
      viable neutrophils from the high-dosage steroid group patients than from the low
      dosage steroid group patients tended to undergo necrosis, followed by the release
      of neutrophil elastase after exposure to E. coli. The levels of anti-inflammatory
      cytokines were not enhanced after E. coli stimulation, but the levels of
      proinflammatory cytokines in the supernatants of neutrophils from the high-dosage
      steroid group patients were increased significantly. CONCLUSION: Steroid
      overdosed UC patients with MIF-related neutrophil dysfunction may be at increased
      risk of destructive local inflammation following surgery.

PMID- 21969154
TI  - Impact of endoscopic and histological evaluations of two different types of mesh
      plug for a groin hernia model.
AB  - PURPOSE: The biological responses to mesh in vivo have been evaluated in some
      papers, but the in vivo condition of mesh and plugs have not been sufficiently
      evaluated. This study evaluated the endoscopic observations and histological
      assessments of mesh plugs using swine models. METHODS: An artificial abdominal
      hernia was established in the porcine abdomen, and repaired using three different
      sizes of two types of plug, Proloop (ATRIUM Medical Corporation, Hudson, NH, USA)
      or Perfix (BARD Medical Division, Covington, GA, USA). The in vivo conditions of
      each plug were periodically observed using a laparoscope. Moreover, a
      histological evaluation of the plugs was performed 3 months after implantation.
      RESULTS: The laparoscopic observation revealed that inversion of the plugs
      occurred in 10 out of 18 cases repaired with Perfix, while no case repaired with
      Proloop inverted. The large and medium sizes of Perfix plugs were inclined by an
      average of more than 30 degrees . In addition, the triangular shape of Perfix
      plugs was broken and the vertical/horizontal ratio was enlarged during the
      observation period, while Proloop plugs shrank both vertically and horizontally.
      The inflammatory cell count was significantly lower within the Proloop plugs than
      within Perfix plugs. CONCLUSION: Proloop plugs are apparently superior because
      they are stable even 3 months after implantation.

PMID- 21969155
TI  - Single-incision laparoscopy-assisted surgery for bowel obstruction: report of
      three cases.
AB  - We applied single-incision laparoscopy-assisted surgery for several different
      types of bowel obstruction in selected patients. Before the operation, a long
      nasal tube was inserted for intestinal decompression and assessment of a stenotic
      lesion. A specially-designed instrument for single-incision laparoscopic surgery,
      the SILS Port, was introduced at the umbilicus or proposed ileostomy site. After
      intracorporeal procedures, extracorporeal resection and reconstruction of the
      intestine was performed as needed. Three patients with bowel obstruction due to
      jejunal carcinoma, colonic stenosis, and adhesion underwent single-incision
      laparoscopy-assisted surgery. The port site was used for subsequent
      extracorporeal resection and anastomosis of the jejunum in two patients, and for
      ileostomy in the remaining patient. All of the procedures were completed safely,
      and there were no postoperative complications. Single-incision laparoscopy can
      therefore be applied for selected patients with bowel obstruction. In such cases,
      the preoperative insertion of a long nasal tube for decompression of intestinal
      contents and assessment of the stenotic lesion is necessary.

PMID- 21969156
TI  - Hemophagocytic syndrome after liver transplantation: report of two cases.
AB  - We report two cases of hemophagocytic syndrome (HPS), a rare but fatal
      complication after living-donor liver transplantation (LDLT). Despite their
      recovery from pancytopenia following treatment with steroid pulse therapy,
      granulocyte stimulating factor, and intravenous gamma-globulin, both patients
      died. The outcomes reported in cases published in English are devastating, with
      only 4 survivors among the total 14 patients including ours. Pancytopenia is
      frequently recognized postoperatively in liver transplant recipients, although
      its cause is difficult to establish. When pancytopenia accompanying persistent
      high fever is recognized in LDLT recipients, HPS should be suspected and bone
      marrow aspiration performed as promptly as possible because of the poor prognosis
      of this syndrome. There is still no optimal treatment for HPS after liver
      transplantation.

PMID- 21969157
TI  - Surgical resection following combination chemotherapy with oral S-1 and biweekly
      docetaxel in a patient with advanced gastric cancer and a prior coronary artery
      bypass graft with the right gastroepiploic artery: report of a case.
AB  - Cardiothoracic surgeons commonly use the internal thoracic artery (ITA) and the
      right gastroepiploic artery (RGEA) when performing a coronary artery bypass graft
      (CABG). Although the development of CABG surgery has enabled long-term survival
      in patients with coronary artery disease, malignant diseases are more common in
      older patients. We present the case of a 75-year-old man who had previously
      undergone CABG with the RGEA and had later developed advanced gastric cancer. We
      treated this patient with two courses of combination chemotherapy using S-1 and
      docetaxel as induction therapy, followed by successful tumor resection.
      Therefore, neoadjuvant chemotherapy was effective for preserving the CABG with
      the RGEA in a patient with advanced gastric cancer.

PMID- 21969158
TI  - Laparoscopic right hemicolectomy with D3 lymph node dissection for a patient with
      situs inversus totalis: report of a case.
AB  - Situs inversus totalis (SIT) is a rare congenital anomaly characterized by an
      inversion of the thoracic and abdominal viscera that creates a mirror image. The
      transposition of the organs imposes special demands on the diagnostic and
      technical skills of the surgeon, especially when performing laparoscopic surgery.
      We herein report the case of a 63-year-old man with colon cancer of the hepatic
      flexure who received a laparoscopic right hemicolectomy. Careful recognition by
      the surgeon of the mirror image anatomy and skillful use of his left hand
      resulted in a successful outcome. The surgery was not otherwise different from
      ordinary cases. Therefore, laparoscopic colectomy is considered to be a safe and
      feasible option for patients with colorectal cancer and SIT.

PMID- 21969159
TI  - Single-incision laparoscopic Heller myotomy and Dor fundoplication for achalasia:
      report of a case.
AB  - Our objective was to establish the efficiency of single-incision laparoscopic
      Heller myotomy and Dor fundoplication (SILHD) as treatment for esophageal
      achalasia. A 58-year-old man underwent SILHD for achalasia. The left triangular
      ligament was retracted using a suture thread and fixed to the body surface,
      providing a good operative field at the cardia. We performed a 7-cm long myotomy,
      extending 2 cm into the gastric wall, using a tissue-sealing device or L-shaped
      electrocautery. Oral intake resumed on postoperative day 1, and hospital stay was
      4 days. No morbidity was observed. Based on our experience, we believe that the
      SILHD can be performed safely and seems to offer at least short-term benefits for
      selected patients with esophageal achalasia, when performed by surgeons
      experienced in laparoscopic and esophageal surgery.

PMID- 21969160
TI  - Trans-sacral resection of a solitary fibrous tumor in the pelvis: report of a
      case.
AB  - Solitary fibrous tumors (SFTs) develop most commonly in the pleura, although they
      have occasionally been reported to arise in the pelvic cavity. We report a case
      of an SFT presenting as a painless nodule in the pelvis of a 56-year-old woman.
      Histologically, the tumor was composed of spindle-shaped cells arranged without
      pattern, with short and narrow fascicles and interspersed bundles of thick
      collagen, and numerous blood vessels with a focally hemangiopericytoma-like
      appearance. Immunohistochemically, the tumor cells strongly expressed vimentin,
      CD34, and bcl-2. The tumor was excised via a trans-sacral approach, without
      preoperative transcatheter embolization, and the patient remains well more than 2
      years after her operation. To our knowledge, this is the first case of an SFT in
      the pelvis, which was excised completely via a trans-sacral approach.

PMID- 21969161
TI  - Adenocarcinoma in an intrapancreatic accessory spleen: report of a case.
AB  - We report a case of adenocarcinoma in an intrapancreatic accessory spleen (IPAS).
      A 78-year-old woman presented with abdominal discomfort, and investigations
      revealed an elevated serum carbohydrate antigen 19-9 level, to 161.8 U/ml
      (normal, <37 U/ml). Ultrasonography showed a heterogeneous echogenic tumor with a
      vascular hilum. Computed tomography showed a heterogeneously enhanced tumor, 8 cm
      in diameter, adjacent to the pancreatic body, accompanying a feeding artery
      arising from the splenic artery, and a drainage vein flowing into the splenic
      vein. We performed a distal pancreaticosplenectomy. The tumor was surrounded by a
      fibrous capsule and was in contact with the pancreatic body. Histological
      examinations revealed invasive growth of adenocarcinoma in a structure identical
      to the spleen. The results of both radiological and histological examinations
      suggested that the tumor originated from an intrapancreatic accessory spleen.
      Extensive examinations revealed no other malignancy, based on which we concluded
      that the adenocarcinoma was primary. Surgical intervention is strongly
      recommended when a malignancy in an IPAS cannot be ruled out.

PMID- 21969162
TI  - Leiomyosarcoma of the pancreas: report of a case.
AB  - Leiomyosarcoma of the pancreas is a rare neoplasm, with only 34 reported cases in
      the literature. We encountered a rare case of leiomyosarcoma of the pancreas,
      treated successfully by surgery. A 41-year-old woman was referred to our hospital
      for further examinations of a pancreatic tumor. Imaging studies demonstrated a
      solid and lobular mass, about 4 cm in diameter, in the body of pancreas. This
      mass had a nonuniform content and was encapsulated. We performed distal
      pancreatectomy and splenectomy for an assumed diagnosis of invasive ductal
      carcinoma. Macroscopically, a sagittal section of the operative specimen showed a
      well-circumscribed yellowish-white mass without any cystic changes.
      Immunohistological examination revealed that alpha-smooth muscle actin, desmin,
      and vimentin were positive, and the labeling index of MIB-1 was 50% or more.
      Based on these findings, we confirmed a diagnosis of leiomyosarcoma originating
      from the pancreas. During 14 months of follow-up to date, there has not been any
      evidence of local recurrence or distant metastasis.

PMID- 21969163
TI  - Lymphadenectomy via a cervical approach for upper mediastinal lymph node
      recurrence of esophageal cancer: report of a case.
AB  - Although there have been several reports about salvage esophagectomy after
      definitive chemoradiotherapy (CRT), the effectiveness of lymphadenectomy for
      lymph node recurrence after CRT has not been fully evaluated. Radiation-induced
      tissue injury and fibrosis make lymphadenectomy after CRT difficult, therefore
      the choice of surgical approach should be considered carefully. We performed
      lymphadenectomy via a cervical approach in a 76-year-old man with upper
      mediastinal lymph node recurrence. He had previously undergone subtotal
      esophagectomy for squamous cell carcinoma of the upper thoracic esophagus. At 33
      months after the operation, left upper mediastinal lymph node recurrence
      occurred. After localized CRT with docetaxel plus 60 Gy radiation, the tumor
      disappeared. However, at 1 year after CRT a lymph node recurrence, measuring 10
      mm in size, was found in the same position on a computed tomography (CT) scan and
      (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) without other
      recurrences. Lymphadenectomy was performed via a left cervical approach using a
      Kent retractor to extend the surgical view of the cervicothoracic region. The
      patient was discharged without complications, and a postoperative CT scan and FDG
      PET revealed complete resection of the tumor. In conclusion, our surgical
      procedure provides a good surgical view, and decreases surgical stress and the
      incidence of postoperative complications.

PMID- 21969164
TI  - Transhiatal jejunal interposition preserving the whole stomach and vagal trunk
      for a benign esophageal stricture in a male adolescent: report of a case.
AB  - Benign esophageal strictures are generally treated with medication and balloon
      dilation; however, when repeated dilations fail, surgery is the only option. When
      performing surgery for benign esophageal stricture in young patients, it is
      important to consider not only the surgical stress and likelihood of
      complications but also digestive function after reconstruction, the durability of
      the reconstruction, and the potential for cancerous change in the reconstructed
      organs. We describe how we treated a 14-year-old boy with benign esophageal
      stricture by performing transhiatal esophagectomy assisted by mediastinoscopy,
      preserving the whole stomach and vagus nerve, and interposing pedicled jejunum
      between the cervical esophagus and stomach through a posterior mediastinal route,
      with good long-term results.

PMID- 21969165
TI  - Clinical and pathological analysis of hepatic artery aneurysm in a patient with
      systemic lupus erythematosus: report of a case.
AB  - A hepatic artery aneurysm is an unusual but life-threatening hepatobiliary
      complication occurring in patients with systemic lupus erythematosus (SLE), and
      early diagnosis and treatment of this complication are essential. A 31-year-old
      man with SLE presented with recurring epigastric pain and jaundice for 2 months;
      he was diagnosed with choledocholithiasis and underwent surgery. Hemobilia was
      found intraoperatively, and two hepatic artery aneurysms were identified in the
      left lateral lobe during postoperative arteriography. Major hemobilia occurred 6
      days after the operation, and the patient was immediately treated with selective
      embolization of the hepatic artery. However, the major hemobilia recurred 2 days
      later, and he was treated with a left lateral lobectomy and ligation of the
      proximal hepatic artery. The patient recovered uneventfully and is in good
      condition. A histological analysis revealed small- and medium-sized arteritis as
      well as hepatic artery aneurysm. Systemic lupus erythematosus complicated by a
      hepatic artery aneurysm should be considered in the differential diagnosis of
      patients showing symptoms of abdominal pain, jaundice, or gastrointestinal
      bleeding.

PMID- 21969166
TI  - Bilateral primary breast neuroendocrine carcinoma in a young woman: report of a
      case.
AB  - Bilateral breast carcinoma accounts for approximately 5% of all patients with
      breast cancer, while neuroendocrine breast carcinomas comprise less than 5% of
      invasive breast carcinomas. In addition, most patients with breast neuroendocrine
      carcinomas are older. Therefore, bilateral primary breast neuroendocrine
      carcinoma at a young age is extremely rare. We herein report bilateral
      neuroendocrine carcinoma of the breast in a 29-year-old woman who underwent
      bilateral lumpectomy with the initial symptom of bilateral nipple discharge.
      Grossly, the lesions in both breasts were masses with infinite margins.
      Histologically, this case was consistent with primary neuroendocrine carcinoma
      arising in bilateral breasts. Cells from both breast tumors were positive for
      chromogranin A, neuron-specific enolase, synaptophysin, cytokeratin 7, estrogen
      receptor, and progesterone receptor, and negative for Her2, cytokeratin 34beta12,
      cytokeratin 5/6, smooth muscle actin, p63, S-100 protein, and p53. The Ki67 and
      NE proliferative indices were below 1%. To the best of our knowledge, this is the
      first reported case in China of bilateral primary neuroendocrine carcinoma
      presenting in a young woman.

PMID- 21969167
TI  - Medical teleconference about thoracic surgery using free Internet software.
AB  - Surgical teleconferences using advanced academic networks are becoming common;
      however, reports regarding Internet teleconferencing using free software packages
      such as Skype, USTREAM, and Dropbox are very rare. Teleconferences concerning
      mainly surgical techniques were held five times between Fukuoka University
      Hospital and other institutions from April to September 2010. These
      teleconferences used Skype and USTREAM as videophones to establish communication.
      Both PowerPoint presentations and surgical videos were made. These presentation
      files were previously sent to all stations via mail, e-mail, or Dropbox, and
      shared. A slide-show was simultaneously performed following the presenter's cue
      in each station. All teleconferences were successfully completed, even though
      there were minor instances of the Skype link being broken for unknown reasons
      during the telecommunication. Internet surgical teleconferences using ordinary
      software are therefore considered to be sufficiently feasible. This method will
      become more convenient and common as the Internet environments advance.

PMID- 21969168
TI  - CDH22 expression is reduced in metastatic melanoma.
AB  - Cadherin-like protein 22 (CDH22) is a transmembrane glycoprotein implicated in
      cell-cell adhesion and cancer metastasis. The expression of CDH22 has been shown
      to be increased in colorectal cancers. However, the role of CDH22 in
      melanomagenesis is not known. To investigate the role of CDH22 in melanoma
      progression, we examined the expression of CDH22 in melanocytic lesions at
      different stages and analysed the correlation between CDH22 expression and
      clinicopathlogic parameters and patient survival. Using tissue microarray and
      immunohisto-chemistry, we evaluated CDH22 staining in 76 dysplastic nevi, 247
      primary melanomas, and 143 metastatic melanomas. We found that metastatic
      melanomas had a significantly higher percentage of negative CDH22 staining than
      dysplastic nevi (P = 0.012) and primary melanomas (P = 0.038). CDH22 expression
      was also reduced in thick (>=2 mm) and ulcerative melanomas (P = 0.003 and 0.022,
      respectively). Melanomas of AJCC stage II, III, and IV had a higher percentage of
      negative CDH22 staining than AJCC stage I melanomas (P = 0.004, P < 0.0001, and P
      = 0.009, respectively). Melanomas with negative CDH22 expression had
      significantly poorer disease-specific 5-year survival than those with positive
      CDH22 staining. Additionally, CDH22 expression depended on AJCC stage to predict
      patient survival. These data indicate that reduced CDH22 expression is associated
      with melanoma metastasis and poor patient prognosis.

PMID- 21969169
TI  - beta-sitosterol inhibits high cholesterol-induced platelet beta-amyloid release.
AB  - Recently, increasing evidence has linked high cholesterol to the pathogenesis of
      Alzheimer's disease (AD), suggesting that cholesterol may be a target for
      developing new compounds to prevent or treat AD. Plant sterols, a group of
      sterols enriched in plant oils, nuts, and avocados, have the structure very
      similar to that of cholesterol, and have been widely used to reduce blood
      cholesterol. Due to their cholesterol-lowering property, plant sterols such as
      beta-sitosterol may also influence cholesterol-depending functions including its
      role in AD development. Using human platelets, a type of peripheral blood cells
      containing the most circulating amyloid precursor protein (APP), this study
      investigated the effect of beta-sitosterol on high cholesterol-induced secretion
      of beta amyloid protein (Abeta). It was found that beta-sitosterol effectively
      inhibited high cholesterol-driven platelet Abeta release. In addition, beta
      sitosterol prevented high cholesterol-induced increase of activities of beta- and
      gamma-secretase, two APP cleaving enzymes to generate Abeta. Additional
      experiments showed that high cholesterol up-regulated lipid raft cholesterol.
      This effect of cholesterol could be suppressed by beta-sitosterol. These findings
      suggest that beta-sitosterol is able to inhibit high cholesterol-induced Abeta
      release probably through maintenance of membrane cholesterol homeostasis. Given
      that dietary plant sterols have the potential of penetrating the blood-brain
      barrier (BBB), these data suggest that plant sterols such as beta-sitosterol may
      be useful in AD prevention.

PMID- 21969170
TI  - Combined Oral Contraceptive Pills: Profile of Acceptors in a Tertiary Hospital in
      South-South Nigeria.
AB  - BACKGROUND: Combined oral contraceptive pills were the first contraceptive method
      to provide sexual freedom of choice for women through reliable, personal and
      private control of fertility. They are the most widely used hormonal
      contraceptives and also the most popular non-surgical method of contraception. 
      OBJECTIVE: To review the profile of acceptors of combined oral contraceptive
      pills at the University of Uyo Teaching Hospital, Uyo.  METHODOLOGY: An 8 year
      review of all clients that accepted combined oral contraceptive pills in the
      family planning clinic.  RESULTS: There were 1,146 new contraceptive acceptors
      during the period of study out of which 309 (27.9%) accepted the pills. Majority
      of the clients were between 20 and 29 years of age (54.0%), were multiparous
      (72.8%), Christians (99.7%) and 61.2% had tertiary level education. Two hundred
      and fifty-five women (82.5%) desired to use combined oral contraceptive pills to
      space births while 7.8% wanted to limit child bearing. There was a high
      discontinuation rate among the women (45.0%) and out of these 87.9% of the
      clients changed to other contraceptive methods. All the clients commenced their
      pills within seven days of menstruation and only the low dose monophasic
      preparations were available in the family planning unit and thus were given to
      the clients.  CONCLUSION: Women who accept to initiate combined oral
      contraceptive pills in our center are young, well educated, multiparous women who
      want to space their pregnancies. However, due to the high discontinuation rate
      among the clients, there is need for further studies evaluating reasons for the
      high discontinuation rate, exploring interactions between clients and providers'
      and also providers' attitude towards combined pills in our environment.

PMID- 21969171
TI  - Heat shock protein 10 (Hsp10) in immune-related diseases: one coin, two sides.
AB  - Heat shock protein 10 (Hsp10) in eukaryotes, originally identified as a
      mitochondrial chaperone, now is also known to be present in cytosol, cell
      surface, extracellular space and peripheral blood. Functionally besides
      participating in mitochondrial protein folding in association with Hsp60, Hsp10
      appears to be related to pregnancy, cancer and autoimmune inhibition. Hsp10 can
      be released to peripheral blood at very early time point of pregnancy and given
      another name called early pregnancy factor (EPF), which seems to play a critical
      role in developing a pregnant niche. In malignant disorders, Hsp10 is usually
      abnormally expressed in the cytosol of malignant cells and further released to
      extracellular space, resulting in tumor-promoting effect from various aspects.
      Furthermore, distinct from other heat shock protein members, whose soluble form
      is recognized as danger signal by immune cells and triggers immune responses,
      Hsp10 after release, however, is designed to be an inhibitory signal by limiting
      immune response. This review discusses how Hsp10 participates in various
      physiological and pathological processes from basic protein molecule folding to
      pregnancy, cancer and autoimmune diseases, and emphasizes how important the
      location is for the function exertion of a molecule.

PMID- 21969173
TI  - Coherent control of Forster energy transfer in nanoparticle molecules: energy
      nanogates and plasmonic heat pulses.
AB  - We study how Forster energy transfer from a semiconductor quantum dot to a
      metallic nanoparticle can be gated using quantum coherence in quantum dots. We
      show this allows us to use a laser field to open the flow of the energy transfer
      for a given period of time (on-state) before it is switched off to about zero.
      Utilizing such an energy gating process it is shown that quantum-dot-metallic
      nanoparticle systems (meta-molecules) can act as functional nanoheaters capable
      of generating heat pulses with temporal widths determined by their environmental
      and physical parameters. We discuss the physics behind the energy nanogates using
      molecular states of such meta-molecules and the resonance fluorescence of the
      quantum dots.

PMID- 21969172
TI  - Oxygen dependence of metabolism and cellular adaptation in vertebrate muscles: a
      review.
AB  - The key roles the cardiovascular system play in the complex distribution of
      blood, and consequently oxygen, have been extensively studied in vertebrates.
      Numerous studies have also revealed the complex and varied ways in which tissues
      cope with compromised oxygen supply. The links between these two processes are
      the subject of much current research. This article aims to review how blood
      supply influences tissue oxygenation and affects metabolism, and how this might
      have played a role in the evolution of the complex muscle arrangements which
      characterise vertebrates. Muscle tissue is the greatest proportion of body mass
      in most vertebrates and undergoes dramatic alterations in metabolism and
      associated oxygen flux. Special attention is given to the myotome of fishes, in
      which the partitioning of the fibre types contrasts with the mosaic arrangement
      of tetrapods. This gives us the opportunity to study pure whole vascularised
      muscle blocks, rather than single fibres, and further explore the
      interrelationship between oxygen supply and tissue energetics.

PMID- 21969174
TI  - Organocatalytic asymmetric Michael-type reaction between beta,gamma-unsaturated
      alpha-keto ester and alpha-nitro ketone.
AB  - A Michael-type reaction of beta,gamma-unsaturated alpha-keto ester and alpha
      nitro ketone was established. With a thiourea catalyst derived from cinchona
      alkaloid, the reactions afford products in 47-94% yields with 68-96% ee.

PMID- 21969175
TI  - The efficacy of an HIV risk reduction intervention for Hispanic women.
AB  - Culturally-specific HIV risk reduction interventions for Hispanic women are
      needed. SEPA (Salud/Health, Educacion/Education, Promocion/Promotion, y/and
      Autocuidado/Self-care) is a culturally-specific and theoretically-based group
      intervention for Hispanic women. The SEPA intervention consists of five sessions
      covering STI and HIV prevention; communication, condom negotiation and condom
      use; and violence prevention. A randomized trial tested the efficacy of SEPA with
      548 adult U.S. Hispanic women (SEPA n = 274; delayed intervention control n =
      274) who completed structured interviews at baseline and 3, 6, and 12 months post
      baseline. Intent-to-treat analyses indicated that SEPA decreased positive urine
      samples for Chlamydia; improved condom use, decreased substance abuse and IPV;
      improved communication with partner, improved HIV-related knowledge, improved
      intentions to use condoms, decreased barriers to condom use, and increased
      community prevention attitudes. Culturally-specific interventions have promise
      for preventing HIV for Hispanic women in the U.S. The effectiveness of SEPA
      should be tested in a translational community trial.

PMID- 21969176
TI  - From single to multiple microcoil flow probe NMR and related capillary
      techniques: a review.
AB  - Nuclear magnetic resonance (NMR) spectroscopy is one of the most important and
      powerful instrumental analytical techniques for structural elucidation of unknown
      small and large (complex) isolated and synthesized compounds in organic and
      inorganic chemistry. X-ray crystallography, neutron scattering (neutron
      diffraction), and NMR spectroscopy are the only suitable methods for three
      dimensional structure determination at atomic resolution. Moreover, these methods
      are complementary. However, by means of NMR spectroscopy, reaction dynamics and
      interaction processes can also be investigated. Unfortunately, this technique is
      very insensitive in comparison with other spectrometric (e.g., mass spectrometry)
      and spectroscopic (e.g., infrared spectroscopy) methods. Mainly through the
      development of stronger magnets and more sensitive solenoidal microcoil flow
      probes, this drawback has been successfully counteracted. Capillary NMR
      spectroscopy increases the mass-based sensitivity of the NMR spectroscopic
      analysis up to 100-fold compared with conventional 5-mm NMR probes, and thus can
      be coupled online and off-line with other microseparation and detection
      techniques. It offers not only higher sensitivity, but in many cases provides
      better quality spectra than traditional methods. Owing to the immense number of
      compounds (e.g., of natural product extracts and compound libraries) to be
      examined, single microcoil flow probe NMR spectroscopy will soon be far from
      being sufficiently effective as a screening method. For this reason, an
      inevitable trend towards coupled microseparation-multiple microcoil flow probe
      NMR techniques, which allow simultaneous online and off-line detection of several
      compounds, will occur. In this review we describe the current status and possible
      future developments of single and multiple microcoil capillary flow probe NMR
      spectroscopy and its application as a high-throughput tool for the analysis of a
      large number of mass-limited samples. The advantages and drawbacks of different
      coupled microseparation-capillary NMR spectroscopy techniques, such as capillary
      high-performance liquid chromatography-NMR spectroscopy, capillary
      electrophoresis-NMR spectroscopy, and capillary gas chromatography-NMR
      spectroscopy, are discussed and demonstrated by specific applications. Another
      subject of discussion is the progress in parallel NMR detection techniques.
      Furthermore, the applicability and mixing capability of tiny reactor systems,
      termed "microreactors" or "micromixers," implemented in NMR probes is
      demonstrated by carbamate- and imine-forming reactions.

PMID- 21969177
TI  - Liquid|liquid electrochemical bicarbonate and carbonate capture facilitated by
      boronic acids.
AB  - Reversible bicarbonate and carbonate liquid|liquid ion transfer processes from
      aqueous solution into an organic 4-(3-phenylpropyl)pyridine phase are driven
      electrochemically with TPPMn(III/II) and shown to be facilitated over a wide pH
      range by 2-naphthylboronic acid (bicarbonate transfer potential -0.08 V vs. SCE;
      binding constant K(AB) = 10(2) mol(-1) dm(3) and carbonate dianion transfer
      potential 0.07 V vs. SCE; binding constant K(AB2) = 2 * 10(10) mol(-2) dm(6)).

PMID- 21969178
TI  - Exosome/microvesicle-mediated epigenetic reprogramming of cells.
AB  - Microvesicles (MVs) are released by different cell types and may remain in the
      extracellular space in proximity of the cell of origin or may enter the
      biological fluids. MVs released by tumor cells are detectable in patients with
      cancer and their number in the circulation correlates with poor prognosis. Recent
      studies demonstrated that MVs may act as mediator of cell-to-cell communication
      thus ensuring short- and long-range exchange of information. Due to their
      pleyotropic effects, MVs may play a role in the prothrombotic state associated
      with cancer as well as in cancer development and progression. It has been
      recently shown that MVs may induce epigenetic changes in target cells by
      transferring genetic information. This finding suggests that tumor and stromal
      cells may talk each other via MVs to establish a favorable tumor niche and to
      promote tumor growth, invasiveness and progression. Moreover, MVs contain genetic
      material under the form of mRNA and microRNA, that may allow an easy screening
      for cancer genetic markers and offer new diagnostic and prognostic information.
      This review presents an overview of the many biological actions of MVs and of the
      potential role of MV-mediated exchange of genetic information among cells in
      tumor biology.

PMID- 21969179
TI  - In vivo analysis of coracoclavicular ligament kinematics during shoulder
      abduction.
AB  - BACKGROUND: Anatomic reconstruction of the coracoclavicular ligaments for the
      treatment of acromioclavicular joint separations provides superior biomechanical
      stability compared with other procedures. Clavicular and coracoidal footprints of
      the conoid ligament (CL) and the trapezoid ligament (TL) are well described. So
      far, little is known about their kinematics and the changes of the
      coracoclavicular distance during shoulder abduction. HYPOTHESIS: The
      coracoclavicular distance along the coracoclavicular ligaments changes
      significantly with shoulder abduction and weightbearing. STUDY DESIGN:
      Descriptive laboratory study. METHODS: With use of an open magnetic resonance
      imaging scanner, the shoulders of 13 healthy volunteers were examined in supine
      and sitting positions. Three-dimensional magnetic resonance images of the
      shoulders were obtained in 30 degrees  increments of abduction (0 degrees -120
      degrees ). A manual segmentation of the scapula, the clavicle, and the
      coracoclavicular ligaments was performed. The insertion points of the
      coracoclavicular ligaments were identified, and automated measures along the
      ligamentous course were carried out. RESULTS: During transfer from the lying to
      sitting position, the coracoclavicular distance showed significant lengthening of
      3 mm along the center of the CL, which significantly increased another 3 mm
      during shoulder abduction to a total lengthening of 6 mm. In the supine position,
      the coracoclavicular distance along the TL did not elongate significantly. In the
      sitting position, the distance along the medial portion of the TL shortened
      significantly, whereas the distance along the center portion did not elongate
      significantly during shoulder abduction. CONCLUSION: The distances between the
      coracoclavicular insertion points depend on both patient and shoulder
      positioning. To prevent overconstraining of the graft, the CL should be fixated
      during 90 degrees  to 120 degrees  of shoulder abduction in a sitting position.
      Isometric reconstruction of the TL can be achieved if precise fixation of the
      graft at the centers of the conoidal and clavicular footprints is performed.

PMID- 21969180
TI  - Autologous chondrocyte implantation for treatment of cartilage defects of the
      knee: what predicts the need for reintervention?
AB  - BACKGROUND: Autologous chondrocyte implantation (ACI) is a well-established
      treatment option for isolated cartilage defects of the knee joint, providing
      satisfying outcome. However, cases of treatment failure with the need for
      surgical reintervention are reported; typical patient's individual and
      environmental risk factors have previously not been described. HYPOTHESIS: The
      need for reintervention after ACI is associated with specific preoperative
      detectable individual risk factors. STUDY DESIGN: Cohort study; Level of
      evidence, 3. METHODS: A total of 413 patients following ACI (first, second, and
      third generation) were filtered for those who required revision surgery during
      their follow-up time (2-11.8 years). Factors were analyzed that might have
      significant effects on increased revision rate. Using preoperatively collected
      data, all patients were grouped according to 12 standard prognostic factors.
      Apart from odds ratio and Pearson chi(2) test, statistical analysis of risk
      factors was performed with multivariate binary logistic regression models and Cox
      regression, the method of choice for survival time data. RESULTS: After a follow
      up of 4.4 +/- 0.9 years (limited to 5 years), a total of 88 patients (21.3%) had
      undergone surgical revision. The time to revision surgery was 1.8 +/- 1.1 years.
      Four prognostic factors associated with a significantly higher risk for
      reintervention were detected: (1) female gender (Cox survival fit: P = .033), (2)
      previous surgeries of the affected joint (P = .002), (3) previous bone marrow
      stimulation (P = .041), and (4) periosteum patch-covered ACI (P = .028). An
      influence of patient age, body mass index (BMI), defect number, defect size,
      lesion origin, lesion location, parallel treatment, or smoking on the risk for
      reintervention could not be observed. CONCLUSION: The study identifies clear
      facts that significantly increase the risk of revision surgery. These facts can
      be easily obtained preoperatively and may be taken into consideration when
      indicating ACI.

PMID- 21969181
TI  - Assessment and management of sport-related concussions in United States high
      schools.
AB  - BACKGROUND: Little existing data describe which medical professionals and which
      medical studies are used to assess sport-related concussions in high school
      athletes. PURPOSE: To describe the medical providers and medical studies used
      when assessing sport-related concussions. To determine the effects of medical
      provider type on timing of return to play, frequency of imaging, and frequency of
      neuropsychological testing. STUDY DESIGN: Descriptive epidemiology study.
      METHODS: All concussions recorded by the High School Reporting Information Online
      (HS RIO) injury surveillance system during the 2009 to 2010 academic year were
      included. chi(2) analyses were conducted for categorical variables. Fisher exact
      test was used for nonparametric data. Logistic regression analyses were used when
      adjusting for potential confounders. Statistical significance was considered for
      P < .05. RESULTS: The HS RIO recorded 1056 sport-related concussions,
      representing 14.6% of all injuries. Most (94.4%) concussions were assessed by
      athletic trainers (ATs), 58.8% by a primary care physician. Few concussions were
      managed by specialists. The assessment of 21.2% included computed tomography.
      Computerized neuropsychological testing was used for 41.2%. For 50.1%, a
      physician decided when to return the athlete to play; for 46.2%, the decision was
      made by an AT. After adjusting for potential confounders, no associations between
      timing of return to play and the type of provider (physician vs AT) deciding to
      return the athlete to play were found. CONCLUSION: Concussions account for nearly
      15% of all sport-related injuries in high school athletes. The timing of return
      to play after a sport-related concussion is similar regardless of whether the
      decision to return the athlete to play is made by a physician or an AT. When a
      medical doctor is involved, most concussions are assessed by primary care
      physicians as opposed to subspecialists. Computed tomography is obtained during
      the assessment of 1 of every 5 concussions occurring in high school athletes.

PMID- 21969182
TI  - Comparison of beer quality attributes between beers brewed with 100% barley malt
      and 100% barley raw material.
AB  - BACKGROUND: Brewing with 100% barley using the Ondea(r) Pro exogenous brewing
      enzyme product was compared to brewing with 100% barley. The use of barley,
      rather than malt, in the brewing process and the consequences for selected beer
      quality attributes (foam formation, colloidal stability and filterability,
      sensory differences, protein content and composition) was considered. RESULTS:
      The quality attributes of barley, malt, kettle-full-wort, cold wort, unfiltered
      beer and filtered beer were assessed. A particular focus was given to monitoring
      changes in the barley protein composition during the brewing process and how the
      exogenous OndeaPro(r) enzymes influenced wort protein composition. All analyses
      were based on standard brewing methods described in ASBC, EBC or MEBAK. To
      monitor the protein changes two-dimensional polyacrylamide gel electrophoresis
      was used. CONCLUSION: It was shown that by brewing beer with 100% barley and an
      appropriate addition of exogenous Ondea(r) Pro enzymes it was possible to
      efficiently brew beer of a satisfactory quality. The production of beers brewed
      with 100% barley resulted in good process efficiency (lautering and filtration)
      and to a final product whose sensory quality was described as light, with little
      body and mouthfeel, very good foam stability and similar organoleptic qualities
      compared to conventional malt beer. In spite of the sensory evaluation
      differences could still be seen in protein content and composition.

PMID- 21969183
TI  - Synthesis of chiral sulfoximines derived from 3-aminoquinazolinones and their
      catalysis of enantioselective diethylzinc addition to aldehydes.
AB  - A series of sulfoxides were sulfoximinated using oxidative addition of 3
      aminoquinazolinones by lead tetraacetate in the presence of hexamethyldisilazane.
      They were applied for the first time in catalytic enantioselective addition to
      aromatic aldehydes with a product enantiopurity (ee) of 92% in the case of 2
      methoxybenzaldehyde.

PMID- 21969184
TI  - ...As Nigeria Strives Towards a Better Health Care in the 21 Century.

PMID- 21969185
TI  - A placenta growth factor 2 variant acts as dominant negative of vascular
      endothelial growth factor A by heterodimerization mechanism.
AB  - Angiogenesis is one of the crucial events for cancer development and growth and
      vascular endothelial growth factor (VEGF) family plays an essential role in this
      biological phenomenon. The members of VEGF family mainly involved in angiogenesis
      are VEGF-A, VEGF-B and placental growth factor (PlGF), which exert their activity
      through the binding and activation of two VEGF receptors, VEGFR-1 and VEGFR-2.
      Human VEGF-A and PlGF are expressed in different isoforms and have the
      peculiarity to form heterodimer if co-expressed in the same cell. The difference
      of two main human PlGF isoforms, PlGF1 and PlGF2, consist in the exclusive
      ability of PlGF2 to bind heparin and Neuropilin receptors. As previously reported
      for PlGF1 isoform, we have generated a PlGF2 variant named PlGF2 -DE, in which
      the residues D(72) and E(73) were substituted with alanine, that is unable to
      bind and activate VEGFR-1 but is still able to heterodimerize with VEGF. Here we
      report that overexpression in VEGF-A producing human tumor cell line derived from
      ovarian carcinoma (A2780) of PlGF2-DE variant by stable transfection,
      significantly reduces the production of VEGF-A homodimer via heterodimerization,
      determining a strong inhibition of xenograft tumor growth and associated
      neoangiogenesis, as well as significant reduction of monocyte-macrophage
      infiltration. Conversely, the overexpression of PlGF2wt, also reducing the VEGF-A
      homodimer production comparably to PlGF2-DE variant through the generation of
      VEGF-A/PlGF2 heterodimer, does not inhibit tumor growth and vessel density
      compared to control, but induces increase of monocyte-macrophage infiltration.
      Interestingly the comparison of PlGF2wt with PlGF1wt overexpression evidences a
      significant reduction of monocyte-macrophages recruitment as unique difference
      among the activity of the two PlGFwt isoforms. Therefore, the 'less soluble'
      PlGF2 shows a limited potential in monocyte-macrophages recruitment. In
      conclusion data here reported demonstrate that PlGF-DE variant acts as 'dominant
      negative' of VEGF-A independently from the PlGF isoform utilized, that the
      expression of active PlGF2 homodimer and VEGF-A/PlGF2 heterodimer is sufficient
      to rescue pro-angiogenic activity lost for reduction of VEGF-A due to
      heterodimerization mechanism, and that PlGF2 shows lower activity into
      recruitment of monocyte-macrophage cells compared to PlGF1 isoform.

PMID- 21969186
TI  - Co-polymerization of penta-halogenated phenols in humic substances by catalytic
      oxidation using biomimetic catalysis.
AB  - INTRODUCTION: A synthetic water-soluble meso-tetra(2,6-dichloro-3
      sulfonatophenyl)porphyrinate of iron(III) chloride, Fe-(TDCPPS)Cl, was employed
      to catalyze the oxidative co-polymerization of penta-halogenated phenols in two
      humic materials of different origin. MATERIALS AND METHODS: Co-polymerization of
      pentachlorophenol (PCP) was followed by high-performance size-exclusion
      chromatography (HPSEC), the unbound PCP recovered from reacting humic solutions
      was evaluated by gas-chromatography/electron capture detector, and the oxidative
      catalyzed coupling of pentafluorophenol (PFP) into humic matter was assessed by
      liquid-state (19)F-NMR spectroscopy. HPSEC showed that the catalyzed oxidative
      coupling between PCP and humic molecules increased the apparent weight-average
      molecular weight (M(w)) values in both humic substances. RESULTS AND DISCUSSION:
      HPSEC further indicated that the co-polymerization reaction turned the loosely
      bound humic supramolecular structures into more stable conformations, which could
      no longer be disrupted by the disaggregating effect of acetic acid. The
      occurrence of covalent linkages established between PCP and humic molecules was
      also suggested by the very little amount of PCP found free in solution after the
      catalyzed co-polymerization. (19)F-NMR spectroscopy suggested that also PFP could
      be oxidatively coupled to humic materials. PFP-humic co-polymerization reaction
      produced (19)F-spectra with many more (19)F signals and wider chemical shifts
      spread than for PFP alone or PFP subjected to catalyzed coupling without humic
      matter. CONCLUSIONS: These findings show that biomimetic iron-porphyrin is an
      efficient catalyst for the covalent binding of polyhalogenated phenols to humic
      molecules, thereby suggesting that the co-polymerization reaction may become a
      useful technology to remediate soils and waters contaminated by polyhalogenated
      phenols and their analogues.

PMID- 21969187
TI  - Current status of HTLV-1 infection.
AB  - It is 30 years since human T-cell leukemia virus type 1 (HTLV-1) was identified
      as the first human retrovirus. To assess the implications of the virus for human
      health it is very important to know the past and present prevalence. Most of the
      estimates of HTLV-1 prevalence are based on serological screening of blood
      donors, pregnant women and other selected population groups. The widely cited
      estimate that the number of HTLV-1 carriers in Japan is 1.2 million was
      calculated from data that are now more than 25 years old. Here I summarize
      previous reports of prevalence studies in the world and Japan. Then, a recent
      analysis of seroprevalence of healthy blood donors in Japan will be described in
      comparison with that of 1988. A decrease in the number of HTLV-1 carriers in
      Japan was demonstrated, however, it is still more than one million. The number
      has increased in the metropolitan areas, probably reflecting the migration of
      Japanese population. I conclude that there is a paucity of general population
      data in countries where HTLV-1 is endemic, and re-evaluation of HTLV-1 infection
      is required to understand the virus burden on the human health.

PMID- 21969188
TI  - Guest editorial: a new era of ATL and HTLV-1 research.

PMID- 21969189
TI  - Laparoscopic surgery for rectal cancer: review of published literature 2000-2009.
AB  - We reviewed seven reports of laparoscopic low anterior resection (LAR) alone for
      rectal cancer and 18 reports of laparoscopic surgery, including LAR. We examined
      the length of surgery, blood loss during surgery, conversion rate to open
      surgery, incidence of anastomotic leakage, morbidity, mortality, and local
      recurrence, and the 5-year overall survival rates. The values were as follows
      (range): length of surgery, 107-540 min vs 23-780 min; blood loss, 0-600 ml vs 0
      1800 ml; conversion to open surgery, 0%-14.0% vs 1.0%-21.9%; anastomotic leakage,
      0%-23.0% vs 3.0%-17.0%; morbidity, 6.1%-38.6% vs 5.8%-40.0%; mortality, 0%-2.0%
      vs 05-5.8%; and local recurrence, 1.4%-6.8% vs 0.95%-20.8%, respectively, in the
      LAR alone vs laparoscopic surgery groups. The 5-year overall survival rates of
      patients with stage I, II, III, and IV disease were 92%-98%, 79%-81%, 67%-89%,
      and 0%-15%, respectively, in the LAR alone group versus 85.4%-100%, 61.7%-94.4%,
      53.7%-78%, and 0%-44.6%, respectively, in the laparoscopic surgery group. Thus,
      we demonstrated the safety and efficacy of laparoscopic surgery for rectal
      cancer.

PMID- 21969190
TI  - Pure laparoscopic right hepatectomy in the semi-prone position using the
      intrahepatic Glissonian approach and a modified hanging maneuver to minimize
      intraoperative bleeding.
AB  - PURPOSE: Although laparoscopic liver resection has been widely adopted,
      performing a pure laparoscopic right hepatectomy remains a challenging procedure.
      The aim of this report is to evaluate the efficiency of a pure laparoscopic right
      hepatectomy (PLRH) in the semi-prone position using the intrahepatic Glissonian
      approach and a modified hanging maneuver. METHODS: Pure laparoscopic right
      hepatectomy was performed in the semi-prone position with the use of an
      intrahepatic Glissonian approach and modified hanging maneuver for patients with
      primary liver cancer (n = 3) and metastatic liver cancer (n = 1). RESULTS: The
      intraoperative total blood loss was only 95-140 g (mean: 126.2 g). None of the
      patients required a blood transfusion, and no serious complications were
      encountered. The durations of the surgeries ranged from were 308 to 445 min
      (mean: 394.8 min). The postoperative hospital stay was 8-11 days (mean 9.5 days).
      CONCLUSION: Pure laparoscopic right hepatectomy in the semi-prone position using
      the intrahepatic Glissonian approach and a modified hanging maneuver is thus
      considered to be a safe modality, which minimizes intraoperative bleeding.

PMID- 21969191
TI  - Prognosis and therapeutic response according to the World Health Organization
      histological classification in advanced thymoma.
AB  - PURPOSE: The clinical efficacy of the World Health Organization (WHO)
      classification of thymoma has been reported to be a prognostic factor for
      patients with thymomas. This study focuses on the relationship between the
      therapeutic response and the WHO histological classification in patients with
      advanced thymoma. METHODS: A retrospective review was performed on 22 patients
      with Masaoka stage III and IV thymoma treated from 1975 to 2007. There were 1, 1,
      7, 3, and 10 patients with WHO histological subtypes A, AB, B1, B2, and B3,
      respectively. RESULTS: Surgery was performed on 10 patients. There were 2
      complete resections, 2 incomplete resections, and 6 exploratory thoracotomies. Of
      18 patients with unresectable tumors, 8, 5, and 5 were treated with radiotherapy,
      chemotherapy, and chemoradiotherapy as the initial therapy, respectively. The
      response rate in 9 patients with type A-B2 was significantly better than that in
      9 patients with type B3 regardless of treatment modality (100% vs 11.1%, P =
      0.0001). Only the WHO classification was significantly associated with survival,
      with type B3 having a worse prognosis than A-B2 (P = 0.01). CONCLUSIONS: Type B3
      thymoma showed a lower response rate to treatments and thus shorter survival. The
      WHO classification is a good predictive factor for therapeutic response in
      advanced thymoma.

PMID- 21969192
TI  - Mid-term results of endovascular abdominal aortic aneurysm repair: is it possible
      to predict sac shrinkage?
AB  - PURPOSE: To evaluate the mid-term results of endovascular repair of abdominal
      aortic aneurysms and to predict subsequent sac shrinkage. METHODS: From December
      2006 to April 2010, 114 abdominal aortic aneurysms were treated with stent
      grafts. The intraoperative sac pressure was measured by a microcatheter.
      Correlations between the diameter change and relevant factors were determined by
      a logistic regression analysis. RESULTS: Stent grafts were deployed successfully
      in all patients. Type-2 endoleaks were noted in 25 patients (22%); there were no
      type-1 or type-3 endoleaks at discharge. The clinical success rate was 99%. The
      diameter was reduced in 40 patients (56%) but remained unchanged in 32 (44%).
      There were no aneurysms that increased in diameter. At 2 years after the repair
      the rate of cumulative survival was 87% and freedom from secondary intervention
      was 95%. The sac pressure index after stent grafting with a reduced diameter was
      0.56 +/- 0.11 and that of patients with an unchanged diameter was 0.52 +/- 0.14.
      There were no significant differences between the two groups. Persistent type-2
      endoleaks had a slightly negative effect on sac shrinkage (P = 0.052).
      CONCLUSIONS: The mid-term results of endovascular aneurysm repair were
      satisfactory. Although it was difficult to predict the fate of a sac after stent
      grafting, persistent type-2 endoleaks were observed to have a slightly negative
      impact on sac shrinkage.

PMID- 21969193
TI  - A multicenter phase II clinical study of oxaliplatin, folinic acid, and 5
      fluorouracil combination chemotherapy as first-line treatment for advanced
      colorectal cancer: a Japanese experience.
AB  - PURPOSE: This multicenter phase II study was designed to determine the efficacy
      and tolerability of oxaliplatin in combination with levofolinate and infusion 5
      fluorouracil (FOLFOX4) as first-line therapy for Japanese patients with
      unresectable metastatic colorectal cancer. METHODS: Sixty consecutive patients
      with histologically confirmed advanced or metastatic colorectal cancer were
      enrolled in the study. Treatment was repeated every 2 weeks until disease
      progression or unacceptable toxicity occurred. RESULTS: Two patients were
      ineligible. Toxicity was evaluated in 60 patients, who had received a part or all
      of the protocol therapy. A partial response was observed in 20 patients. The
      overall response rate was 34.5% (95% CI, 22.5%-48.1%) and the tumor control rate
      (partial response + stable disease) was 82.8%. The median progression-free
      survival was 6.9 months (95% CI, 5.1-9.8 months), and the median overall survival
      was 31.5 months (95% CI, 18.1-40.1 months). There were no toxicity-related
      deaths. Grade 3 or 4 neutropenia occurred in 48.3% of patients and often caused a
      delay in the subsequent treatment course. Mild to moderate cumulative peripheral
      sensory neuropathy affected 71.7% of patients. CONCLUSION: The results showed
      good tolerability and efficacy for first-line FOLFOX4 in the treatment of
      patients with advanced colorectal cancer, indicating the promise of this regimen
      as first-line therapy for advanced colorectal cancer in the Japanese population.

PMID- 21969194
TI  - Remifentanil and glucose suppress inflammation in a rat model of surgical stress.
AB  - PURPOSE: Postoperative stress produces an inflammatory response. Recent studies
      have shown that narcotic analgesics suppress the immune system. Nutritional
      management during perioperative care has also been reported to affect
      inflammation. We therefore examined whether remifentanil or glucose
      administration could ameliorate postsurgical inflammatory responses using a rat
      model of surgical stress. METHODS: We divided male Wistar rats randomly into five
      groups: (1) control, (2) sevoflurane+lactated Ringer's solution, (3)
      sevoflurane+lactated Ringer's solution with 1% glucose, (4)
      sevoflurane+remifentanil+lactated Ringer's solution, and (5)
      sevoflurane+remifentanil+ lactated Ringer's solution with 1% glucose. In all
      groups, serum samples were obtained at various time points after surgery, and
      secreted cytokine concentrations were determined. In addition, we assessed the
      activation of protein kinase B (Akt) and forkhead/winged helix box class O
      (FOXO3), which play a role in gluconeogenesis/stress responses. RESULTS: Surgical
      stress increased the serum concentrations of tumor necrosis factor-alpha and
      interleukin-6. Groups receiving remifentanil with anesthesia showed an attenuated
      inflammatory response. The inflammatory response was also reduced by
      administering 1% glucose. Furthermore, 1% glucose induced Akt and FOXO3
      phosphorylation in the quadriceps femoris muscle 12 h after surgery. CONCLUSIONS:
      Anesthesia based on remifentanil and perioperative administration of lactated
      Ringer's solution containing 1% glucose may be able to control inflammatory
      responses caused by surgical stress.

PMID- 21969196
TI  - Rupture of a congenital diaphragmatic eventration in a child: report of a case.
AB  - Diaphragmatic rupture may be traumatic or may occur spontaneously. Spontaneous
      diaphragmatic rupture is a rare entity seen almost entirely in adults. We report
      here a case with spontaneous rupture of a congenital diaphragmatic evantration in
      a child.

PMID- 21969195
TI  - Roles of vascular endothelial growth factor and endothelial nitric oxide synthase
      during revascularization and regeneration after partial hepatectomy in a rat
      model.
AB  - PURPOSE: Angiogenesis is an essential process in liver regeneration. Nitric oxide
      (NO) and vascular endothelial growth factor (VEGF) are the main regulators of
      normal and pathological angiogenesis. This study aimed to determine the roles of
      NO derived from endothelial nitric oxide synthase (eNOS) and VEGF in sinusoidal
      endothelial cell (SEC) proliferation during liver regeneration. METHODS: Sprague
      Dawley rats underwent a 70% partial hepatectomy (PHx), and were euthanized 0, 24,
      48, 72, or 168 h later. Liver regeneration and SEC proliferation were evaluated.
      The protein expression of VEGF and eNOS was examined by a Western blot analysis.
      The rats were also treated with the NO synthase inhibitor N (G)-nitro-L-arginine
      methyl ester (L-NAME) to examine its effects on liver regeneration and SEC
      proliferation. RESULTS: The proliferating cell nuclear antigen (PCNA) labeling
      index of hepatocytes was significantly increased at 24 h after PHx. The eNOS
      protein expression and NO production were significantly increased from 72 to 168
      h. The expression of VEGF protein was significantly increased at 72 h. L-NAME
      significantly inhibited the increases in the liver mass and decreased the PCNA
      labeling index of hepatocytes at 24 h. L-NAME also inhibited the induction of
      VEGF protein at 72 h. CONCLUSIONS: Endothelial NOS and VEGF coordinately regulate
      SEC proliferation during liver regeneration. Sinusoidal endothelial cell
      proliferation is necessary and is an important step in liver regeneration.

PMID- 21969197
TI  - Laparoscopy-assisted resection of an undiagnosed liver tumor and ascending colon
      cancer via mini median laparotomy: report of a case.
AB  - We describe how we resected a hepatic angiomyolipoma and ascending colon cancer
      synchronously via laparoscopic left lateral segmentectomy and laparoscopic right
      colectomy, respectively. The patient was a 72-year-old man, admitted to our
      hospital after a liver tumor and ascending colon cancer were detected during a
      general health check. Computed tomography (CT) showed a hypervascular liver tumor
      mimicking hepatocellular carcinoma, 2 cm in diameter, in segment 3 of the liver.
      The ascending colon cancer was diagnosed as T2N0M0, Stage I. The left lateral
      liver and right colon were mobilized laparoscopically and hepatic transaction,
      followed by resection and anastomosis of the colon, were performed
      extracorporeally through the same 7-cm upper median incision. This type of
      laparoscopy-assisted combined resection is useful to obtain a pathological
      diagnosis of the liver tumor and to remove the entire tumor in a minimally
      invasive and cosmetic manner.

PMID- 21969199
TI  - Idiopathic encapsulating peritonitis: report of two cases.
AB  - This report presents two cases of young males who developed the rare idiopathic
      form of sclerosing encapsulating peritonitis (SEP) presented as partial bowel
      obstruction, both diagnosed during surgical treatment, with satisfactory
      outcomes. Sclerosing encapsulating peritonitis is a rare and enigmatic condition,
      characterized by intraperitoneal fibrosclerosis, which causes intestinal
      obstruction. It is a chronic entity with a poorly elucidated pathophysiology,
      leading to the constitution of a thick white nacreous fibrosis membrane that
      wraps the bowel in a concertina-like fashion with some adhesions configuring an
      intra-abdominal cocoon. Sclerosing encapsulating peritonitis is reported in a
      wide variety of patients, including those who have undergone peritoneal dialysis,
      young adolescent girls, cirrhotic patients after peritoneal-venous shunting, and
      patients treated with beta-blockers. Nevertheless, the etiology of SEP remains
      obscure. This entity presents many difficulties in preoperative diagnosis because
      of its peculiar characteristics. Recognition of the SEP results in proper
      management and prevents unnecessary bowel resection. Regardless of cause, the
      treatment of the obstruction is surgical, with dissection of the encasing
      membrane from the intestine and separation of adherent loops of small bowel until
      they are laid free and returned to their normal configuration. The prognosis
      after appropriate surgical therapy is good, but depends on coexisting diseases.

PMID- 21969198
TI  - Management of chylous leakage after breast surgery: report of four cases.
AB  - Chylous leakage is a rare occurrence after breast surgery. Trauma to the thoracic
      duct and its main distribution may be the main cause of chylous leakage, but the
      cause of such an injury during breast surgery is unknown. We herein report the
      first case of chylous leakage from many minimal lymph ducts in a skin flap. In
      all, four cases of chylous leakage were observed out of 1 096 breast cancer
      patients who underwent axillary lymph node dissection. Of these four cases, three
      cases were successfully treated conservatively; however, surgical exploration was
      performed in the fourth case because of the large drainage volume. Furthermore,
      we reviewed the recently published studies on chylous leakage after breast
      surgery; 20 cases (our 4 cases included) have been reported in all. Of the 20
      pooled cases, most were cured with conservative treatment and only three cases
      were cured with surgical treatment.

PMID- 21969200
TI  - Primary superficial femoral vein leiomyosarcoma: report of a case.
AB  - The majority of leiomyosarcomas occur in the muscular layers of the
      gastrointestinal tract and uterus. Primary leiomyosarcomas rarely arise in the
      veins of the lower extremities. Primary leiomyosarcoma of the superficial femoral
      vein is extremely uncommon. We herein present a case of a 69-year-old man with a
      primary leiomyosarcoma of the superficial femoral vein of his left thigh, which
      manifested as an anteromedial palpable painless mass in the middle third of his
      left thigh. Duplex ultrasonography revealed a 4 * 8-cm mass attached to the left
      superficial femoral vein. The mass was removed surgically en bloc. Histological
      examination showed a low-grade leiomyosarcoma. Seven months after the resection,
      a local recurrence of the tumor was observed, and the patient underwent another
      surgery. Five years after the second operation the patient remains free of
      illness.

PMID- 21969201
TI  - Primary neuroendocrine tumor in the liver treated by hepatectomy: report of a
      case.
AB  - A 49-year-old woman was admitted to our hospital under suspicion of an enlarging
      hepatic tumor, which had been previously diagnosed to be a cavernous hemangioma.
      Computed tomography revealed three enhanced tumors, one measuring 15 cm in
      diameter within the right lobe of the liver and two intrahepatic metastases in
      Couinaud's hepatic segments 3 and 5. We diagnosed the patient to have primary
      liver cancer, and suspected a combined liver tumor preoperatively. We performed a
      right trisectionectomy with radiofrequency ablation of the intrahepatic
      metastasis in S3. According to the immunohistochemical findings of the resected
      specimen and the findings of postoperative imaging studies, the tumor was
      diagnosed to be a primary neuroendocrine tumor in the liver. The patient is
      presently alive without recurrence at 33 months after the operation.

PMID- 21969202
TI  - Successful management of a large bronchopleural fistula after lobectomy: report
      of a case.
AB  - The development of bronchopleural fistula after pulmonary resection is a well
      known complication associated with a high mortality rate. We herein describe the
      successful management of a bronchopleural fistula using a rib and intercostal
      muscle in a patient with a large stump opening of 25 mm in diameter. A flap with
      rib and intercostal muscle is useful for large bronchopleural fistulas to avoid
      airway stenosis.

PMID- 21969203
TI  - Ileal metastasis of breast cancer in a patient with a BRCA2 gene mutation: report
      of a case.
AB  - Breast cancer is the most common malignancy in females. Common sites of
      metastases include the liver, lung, bone, and brain, while metastases to the
      extrahepatic digestive system are very rare. This report presents a patient
      diagnosed with breast carcinoma metastasis in the terminal ileum. The patient
      underwent breast-conserving surgery on both breasts because of breast cancer at
      the age of 46 years. Both breast cancers were consistent with stage I invasive
      ductal carcinomas. Colonoscopy during an investigation for hematochezia revealed
      a 2-cm ulceration in the terminal ileum 22 months later, and microscopic
      examination of a biopsy specimen of the ulceration revealed a poorly
      differentiated mass that was strongly suggestive of metastatic adenocarcinoma
      with endolymphatic tumor emboli. She underwent hand-assisted laparoscopic
      ileocecectomy because of ileal metastasis. She had a family history of breast
      cancer (sister) and colon cancer (brother). She exhibited HER2/neu discordance
      and carried the BRCA2 gene mutation. Surgeons should remain aware that breast
      cancer can metastasize to the gastrointestinal tract.

PMID- 21969204
TI  - Combined hepatic resection with the inferior vena cava and diaphragm and
      reconstruction using an equine pericardial patch: report of a case.
AB  - We herein report a case of combined hepatic resection with inferior vena cava
      (IVC) and diaphragm resection, and reconstruction using an equine pericardial
      patch. A 54-year-old woman showed hepatic cancer recurrence on radiological
      imaging, with invasion to the caudate lobe of the liver, IVC, diaphragm, and
      adrenal gland. We resected 10 * 5 cm of the diaphragm. After dissecting the
      hepatic parenchyma, the caudate lobe was connected only to the IVC. Clamping of
      the IVC was performed between the IVC below the confluence of the hepatic vein
      and the suprarenal IVC. A 6 * 3-cm segment of the IVC was then resected. The IVC
      and diaphragm were reconstructed using an equine pericardial patch, as both
      defects were too large to repair without a patch. The equine pericardium
      represents a suitable graft material for repairing both the IVC and diaphragm.
      Further investigation is needed to determine the durability and anti-infection
      properties of equine pericardial grafts.

PMID- 21969205
TI  - Extensively spreading intraepithelial bile duct carcinoma causing multiple bile
      duct strictures: report of three cases.
AB  - Extensive intraepithelial spread of bile duct carcinoma is a common feature, seen
      in approximately 18% of all cases. However, this spread is rarely accompanied by
      bile duct strictures. We herein describe three cases of bile duct carcinoma with
      multiple bile duct strictures due to extensive intraepithelial spread. In all
      three cases, the spread of intraepithelial cancer extended into the epithelium of
      the peribiliary glands along the intrahepatic bile ducts with marked fibrosis on
      histopathological examination. It is speculated that peribiliary gland
      involvement by superficially spreading bile duct cancer and subsequent
      obstructive glandular inflammation with fibrosis might cause intrahepatic bile
      duct strictures even without interstitial cancer invasion.

PMID- 21969206
TI  - Immediate extended latissimus dorsi flap reconstruction after skin-sparing
      mastectomy for breast cancer associated with paraffinoma: report of a case.
AB  - Paraffin oil injection into the breast, which had been used for breast
      augmentation in the past, can cause various complications. Complete removal of
      paraffinoma lesions with immediate breast reconstruction using autogenous tissue
      is a very satisfactory treatment option. However, diffuse random distribution of
      paraffin oil through the subdermal layer makes it impossible to remove all of the
      lesions with overlying skin without resulting in a shortage of available skin and
      poor cosmesis. We herein report the case of a patient with breast cancer
      associated with paraffinoma, treated with skinsparing mastectomy and axillary
      node dissection with immediate extended latissimus dorsi flap reconstruction,
      resulting in good cosmetic outcome, and showing no complications during the wound
      healing process.

PMID- 21969207
TI  - Fontan conversion with novel direct ablation after childbirth: report of a case.
AB  - A 38-year-old woman underwent atriopulmonary Fontan surgery at age 18 years and
      subsequently successfully delivered a girl by cesarean section at age 34. Her
      condition later deteriorated due to atrial tachyarrhythmia and progressed to New
      York Heart Association (NYHA) class IV heart failure. Her treatment, at age 36,
      comprised total cavopulmonary connection conversion, direct right atrial ablation
      with bipolar radiofrequency devices, the creation of an atrial septal defect, and
      placement of a dual-chamber permanent pacemaker. Three years after the
      conversion, her condition has improved to NYHA class I.

PMID- 21969208
TI  - Decreased peripheral dendritic cell numbers in dengue virus infection.
AB  - Laboratory predictors of severe forms of dengue virus (DENV) infection are
      needed. These clinical forms seem to be associated with high viremia, stressing
      the importance of immune responses, which could involve dendritic cells (DC).
      Yet, very few studies have evaluated DC after DENV infection. We assessed
      peripheral blood DC subset numbers in mild and severe forms of dengue in 44
      patients, older than 15 years old, infected with serotypes DENV-2, 3 or 4.
      Patients were divided in high, intermediate and no detectable viremia according
      to results of molecular biology amplification of DENV. Serological status of anti
      DENV IgG or IgM determined primary or secondary infections. Plasmacytoid and
      myeloid DC absolute and relative numbers were reduced in infected patients when
      compared to an age-matched healthy control group, but no significant differences
      in DC numbers were observed between mild or severe forms of disease. A severe
      disease was more frequent in patients infected with DENV-2 serotype and with
      secondary infection but no significant differences in DC subset numbers were
      found related to these variables. Viremia levels did not correlate to disease
      severity yet were associated to lower DC numbers. Plasmacytoid DC numbers were
      significantly lower in high and intermediate viremia groups compared to non
      infected controls, but not in no detectable viremia patients. Myeloid DC numbers
      were also significantly lower than controls, even in no detectable viremia
      patients. These results confirm that circulating DC subset numbers are reduced
      after DENV infection, although this is not a biomarker of severe forms of dengue
      in adults.

PMID- 21969209
TI  - Early-life environmental intervention may increase the number of neurons,
      astrocytes, and cellular proliferation in the hippocampus of rats.
AB  - Neonatal handling reduces the stress response in adulthood due to a feedback
      mechanism. The present study analyzed the effects of repeated neonatal
      environmental intervention (daily handling during the first 10 days after birth)
      on neuron-, astroglial cell density, and cellular proliferation of the
      hippocampal (CA1, CA2, and CA3) pyramidal cell layers in female rats. Pups were
      divided into two groups, nonhandled and handled, which were submitted to repeated
      handling sessions between postnatal days 1 and 10. Histological and
      immunohistochemical procedures were used to determine changes in neuron density,
      astroglial cell density, and cellular proliferation. We found an increase in
      neuron density in each pyramidal cell layer of the hippocampus (CA1, CA2, and
      CA3) in female rats (11 and 90 day old) that were handled during the neonatal
      period. Furthermore, we found an increase in astroglial cell density in both
      hemispheres of the brain in the handled group. Finally, we observed an increase
      in cellular proliferation in both hippocampi (CA1, CA2, and CA3) of the brain in
      female pups (11 days old) handled during the neonatal period. This study
      demonstrates that an early-life environmental intervention may induce
      morphological changes in a structure involved with several functions, including
      the stress response. The results of the current study suggest that neonatal
      handling may influence the animals' responses to environmental adversities later
      in life.

PMID- 21969211
TI  - [Occurence and costs of cognitive disorders in Germany].

PMID- 21969212
TI  - [Burnout as a disease category].

PMID- 21969213
TI  - [Dementia - a relevant subject in psychiatric research?].
AB  - OBJECTIVE: Demographic change calls for increased efforts in dementia research.
      METHODS: A systematic analysis of a German-speaking psychiatric journal was
      performed. RESULTS: 18.2 % of all papers published in were related to dementia
      and cognition. CONCLUSIONS: Dementia is a main issue; only papers regarding
      schizophrenia were more common. Health service research is largely lacking.

PMID- 21969210
TI  - Regulation of alpha-secretase ADAM10 expression and activity.
AB  - The amyloid precursor protein (APP) has a pivotal role in pathogenesis of
      Alzheimer's disease (AD) via its beta- and gamma-secretase-derived cleavage
      products--the A-beta peptides. An alternative processing pathway provided by the
      alpha-secretase prevents formation of those toxic peptides and gives rise to the
      neurotrophic and neuroprotective cleavage product APPs-alpha. The molecular
      identity of the alpha-secretase has been confirmed recently, and there is
      consistency about ADAM10 being the most relevant and physiological enzyme of this
      class. It is not clear to what extent a deficiency in the catalytic activity of
      ADAM10 contributes to AD pathology and whether a decline occurs in aging humans.
      Nevertheless, ADAM10 has been suggested as a valuable target for prevention
      and/or for treatment of Alzheimer's disease. This review focuses on our knowledge
      about regulation of ADAM10 on different levels of cell physiology, such as
      transcription and translation, as well as protein-protein interactions and how
      this especially in the case of transcriptional regulation by retinoic acids might
      lead to the development of new therapeutic approaches.

PMID- 21969214
TI  - Development and validation of the Individual Burden of Illness Index for Major
      Depressive Disorder (IBI-D).
AB  - This study aims at developing a single numerical measure that represents a
      depressed patient's individual burden of illness. An exploratory study examined
      depressed outpatients (n = 317) followed by a hypothesis confirmatory study using
      the NIMH STAR*D trial (n = 2,967). Eigenvalues/eigenvectors were obtained from
      the Principal Component Analyses of patient-reported measures of symptom
      severity, functioning, and quality of life. The study shows that a single
      principal component labeled as the Individual Burden of Illness Index for
      Depression (IBI-D) accounts for the vast majority of the variance contained in
      these three measures providing a numerical z score for clinicians and
      investigators to determine an individual's burden of illness, relative to other
      depressed patients.

PMID- 21969215
TI  - Ultrasoft pseudopotentials and projector augmented-wave data sets: application to
      diatomic molecules.
AB  - We test several ultrasoft pseudopotentials (US-PPs) and projector augmented-wave
      (PAW) data sets, calculating the bond lengths, the atomization energies and the
      frequencies of the vibrational stretch modes of various diatomic molecules. The
      US-PPs and the PAW data sets are constructed with the same recipe and using the
      local density approximation or the Perdew, Burke and Ernzerhof generalized
      gradient approximation for the exchange and correlation energies. We study the
      dimers H(2), N(2), O(2), F(2), Al(2), Si(2), P(2), S(2) and Cl(2) and several
      monohydrides, carbides, nitrides and oxides of boron, carbon, nitrogen, oxygen,
      fluorine, aluminum, silicon, phosphorus, sulfur, chlorine, iron and nickel. We
      find that US-PPs and PAW data sets constructed with the same parameters provide
      almost equivalent results for the bond lengths and the vibrational stretch
      frequencies while, for some molecules, the PAW method is superior to the US-PP
      method for the calculation of the atomization energies. Our geometries and
      vibrational frequencies are compared with the results present in the literature
      and obtained by localized basis sets. It is found that the agreement is very
      good, with discrepancies comparable to those due to the use of different
      localized basis sets.

PMID- 21969216
TI  - Sulfur dioxide inhibits excessively activated endoplasmic reticulum stress in
      rats with myocardial injury.
AB  - It has been demonstrated that excessively activated endoplasmic reticulum stress
      (ERS) is related to myocardial injury. The study was designed to explore the
      possible role of sulfur dioxide (SO(2)) in protecting excessively activated ERS
      in rats with isoproterenol (ISO)-induced myocardial injury. Wistar rats were
      randomly divided into control, ISO, and ISO + SO(2) groups. Cardiac
      catheterization-derived hemodynamic parameters and myocardial enzymes in plasma
      were measured. Microstructure changes in myocardial tissues were examined.
      Cardiomyocyte apoptosis was detected by TUNEL method. Myocardial SO(2) content
      and aspartate amino transferase (AAT) activity were detected. Meanwhile, protein
      and mRNA expressions of myocardial AAT1, AAT2, and ERS markers (GRP78, caspase
      12, and CHOP) were evaluated. The results showed that cardiac function was
      decreased, myocardial microstructure was damaged, and myocardial enzyme levels
      and cardiomyocyte apoptosis were increased with a downregulated endogenous
      AAT/SO(2) pathway, and that ERS markers were upregulated at transcriptional and
      translational levels in ISO-treated rats. However, the administration of an SO(2)
      donor, resulting in an increased SO(2) content in myocardial tissues, improved
      cardiac function and myocardial structure, and ameliorated myocardial enzyme
      levels and cardiomyocyte apoptosis associated with a downregulation of
      excessively activated ERS. In conclusion, the endogenous AAT/SO(2) pathway was
      probably responsible for the inhibition of excessively activated ERS, which might
      be involved in the mechanism of ISO-induced myocardial injury.

PMID- 21969217
TI  - Upright T waves in lead aVR are associated with cardiac death or hospitalization
      for heart failure in patients with a prior myocardial infarction.
AB  - The aim of the present study was to clarify the prognostic significance of
      upright T waves (amplitude > 0 mV) in lead aVR in patients with a prior
      myocardial infarction (MI). We retrospectively examined 167 patients with a prior
      MI. The primary end point was cardiac death or hospitalization for heart failure.
      During a follow-up period of 6.5 +/- 2.8 years, 34 patients developed the primary
      end point. A Kaplan-Meier analysis showed a lower primary event-free rate in
      patients with upright T waves in lead aVR than in those with nonupright T waves
      in lead aVR (P = 0.001). Univariate Cox proportional hazards regression analyses
      showed that age, gender, chronic kidney disease, anterior wall MI, upright T
      waves in lead aVR, left ventricular ejection fraction, loop diuretic use, and
      spironolactone use were significantly associated with the primary end point. A
      multivariate Cox proportional hazards regression analysis selected age [hazard
      ratio (HR) 1.10, 95% confidence interval (CI) 1.05-1.16, P < 0.001], upright T
      waves in lead aVR (HR 3.10, 95% CI 1.23-7.82, P = 0.017), and loop diuretic use
      (HR 4.61, 95% CI 1.55-13.67, P = 0.006) as independent predictors of the primary
      end point. In conclusion, the presence of upright T waves in lead aVR is an
      independent predictor of cardiac death or hospitalization for heart failure in
      patients with a prior MI. The analysis of T-wave amplitude in lead aVR provides
      useful prognostic information in patients with a prior MI.

PMID- 21969219
TI  - Combination of 1-methylcyclopropene treatment and controlled atmosphere storage
      retains overall fruit quality and bioactive compounds in mango.
AB  - BACKGROUND: Postharvest application of fungicide prochloraz and hot-water dip are
      commercially practiced to control postharvest diseases in mangoes. Owing to the
      increasing consumer demand for organically produced fruit, the search for natural
      environmentally friendly alternative products and processes has become important
      for the fruit industry. This study evaluated the combined effect of 1
      methylcyclopropene (1-MCP) (500 nL L-1) and controlled atmosphere storage
      conditions (CA-1, 5% O2 + 5% CO2 or CA-2, 3% O2 + 8% CO2) on the maintenance of
      fruit quality and bioactive compounds on hot-water treated mangoes (cv. Kent)
      during postharvest storage. RESULTS: In comparison to the 1-MCP + CA-1 treatment,
      1-MCP + CA-2 reduced the incidence of anthracnose, weight and firmness loss;
      delayed the skin and flesh colour development; prevented the increase of soluble
      solids concentration/titratable acidity ratio, ethanol and acetaldehyde content;
      and maintained the ascorbic acid, carotenoid, total phenolic and flavonoid
      contents, and antioxidant scavenging activity in hot-water treated mangoes. The
      untrained panel preferred 1-MCP + CA-2 treated fruit to the fruit subjected to
      other postharvest treatments adopted in this investigation. CONCLUSION: Our
      investigation suggests that the combined effect of 1-MCP and CA-2 storage can be
      recommended as an alternative treatment to replace prochloraz application for hot
      water treated mangoes and can be adopted commercially for organic export markets.

PMID- 21969218
TI  - Harnessing the cell death pathway for targeted cancer treatment.
AB  - Genotoxic agents have long targeted apoptotic cell death as a primary means of
      treating cancer. However, the presence of cellular defects in many cancers has
      contributed to an acquired resistance to apoptotic cell death, lowering the
      effectiveness of chemo- and radiotherapies. The mechanisms by which cells achieve
      this resistance to treatment are still being investigated, but an alternative
      approach is the study of cell death pathways that are mechanistically distinct
      from apoptosis. These pathways, including autophagy and necrosis, have arisen as
      attractive targets for cancer therapy. This review will discuss apoptosis,
      autophagy, and necrosis in the context of tumorigenesis and drug resistance, as
      well as provide an up-to-date preclinical and clinical review of inhibitors
      targeting these cell death pathways for multiple cancer types. The goal of these
      studies is to identify molecular targets that will enhance the efficacy and
      specificity of current cancer therapies.

PMID- 21969220
TI  - Biomarkers for drug-induced renal damage and nephrotoxicity-an overview for
      applied toxicology.
AB  - The detection of acute kidney injury (AKI) and the monitoring of chronic kidney
      disease (CKD) is becoming more important in industrialized countries. Because of
      the direct relation of kidney damage to the increasing age of the population, as
      well as the connection to other diseases like diabetes mellitus and congestive
      heart failure, renal diseases/failure has increased in the last decades. In
      addition, drug-induced kidney injury, especially of patients in intensive care
      units, is very often a cause of AKI. The need for diagnostic tools to identify
      drug-induced nephrotoxicity has been emphasized by the ICH-regulated agencies.
      This has lead to multiple national and international projects focusing on the
      identification of novel biomarkers to enhance drug development. Several
      parameters related to AKI or CKD are known and have been used for several
      decades. Most of these markers deliver information only when renal damage is well
      established, as is the case for serum creatinine. The field of molecular
      toxicology has spawned new options of the detection of nephrotoxicity. These new
      developments lead to the identification of urinary protein biomarkers, including
      Kim-1, clusterin, osteopontin or RPA-1, and other transcriptional biomarkers
      which enable the earlier detection of AKI and deliver further information about
      the area of nephron damage or the underlying mechanism. These biomarkers were
      mainly identified and qualified in rat but also for humans, several biomarkers
      have been described and now have to be validated. This review will give an
      overview of traditional and novel tools for the detection of renal damage.

PMID- 21969221
TI  - Epigenetic reprogramming of Myc target genes.
AB  - Myc protein plays a fundamental role in regulation of cell cycle, proliferation,
      differentiation and apoptosis by modulating the expression of a large number of
      targets. Myc binding to its targets depends on the presence of the E-box binding
      sequence and by a chromatin context in which histone H3K4me3 lysine methylation
      favors Myc binding. Myc role in transcription is still an open question since Myc
      is able to either activate or repress target genes and the molecular mechanisms
      by which it exerts these functions span from chromatin remodeling to processive
      RNAPII elongation. Since the types and number of enzymes able to reversibly
      modify histones is recently growing, some of the acquisitions regarding Myc
      chromatin remodeling properties are being revaluated. Here, we summarize recent
      findings regarding the function of Myc in epigenetic reprogramming of its targets
      in transcription of differentiated as well as pluripotent cells.

PMID- 21969222
TI  - Psychosocial Impact of disclosure of HIV Serostatus in heterosexual relationship
      at the Lagos University teaching Hospital, Nigeria.
AB  - OBJECTIVES: To determine the rate and pattern of disclosure and non disclosure of
      HIV serostatus among people living with HIV and the psychosocial impact of
      disclosure.  METHODS: Participants were drawn from the adult HIV clinic at the
      Lagos University Teaching Hospital, Lagos, Nigeria. An interviewer-administered
      questionnaire was used to collect data from consenting participants that included
      socio-demographic information, pattern and reason for non-disclosure and the
      possible consequences of disclosure of HIV serostatus to their sexual partners. 
      RESULTS: Four hundred and ninety nine respondents with a mean age of 37.3 +/- 9.6
      years were recruited into the study. There were 157 males and 342 females.
      Majority of the participants were married (62%) and belonged to the low socio
      economic class. Overall 61.5% (307 of 499) had disclosed their status to sex
      partner(s). Gender, social class and length of year of diagnosis were not
      associated with disclosure but number of sexual partners was strongly associated
      with non disclosure. P=0.0063. The most common reason for non-disclosure was fear
      of rejection (65%). Majority (96.7%) of those who disclosed their status had no
      regret and majority (81.1%) of those who had not disclosed had protected sex.
      After counseling, only18.8% (36 of 192) of those that had not disclosed thought
      that the counseling had helped them overcome the fear of disclosure and were
      willing to disclose.  CONCLUSION: Many people would disclose their HIV serostatus
      to sex partner(s). Protected sex (through the use of condom) is widely accepted
      in our setting.

PMID- 21969223
TI  - "ECG variability contour" method reveals amplitude changes in both ischemic
      patients and normal subjects during Dipyridamole stress: a preliminary report.
AB  - To detect and quantify consistent ECG amplitude changes, the "ECG variability
      contour" (EVC) method was proposed. Using this method we investigated amplitude
      changes in subjects undergoing myocardial perfusion imaging (MPI) with
      Dipyridamole (Dp). Fifty-three patients having reversible perfusion defects and
      19 normal subjects (NS) who were free of: perfusion defects on their MPI,
      standard ST-T changes during Dp stress, and a negative clinical follow up. Mean
      ?1(<?1>) was similar for the NS and patient group (6.2 +/- 6.1 vs. 6.3 +/- 6.2, P
      = 0.95). <?1> was 4.6 +/- 3.0 in patients not having ST-T changes during Dp
      stress (n = 42), whereas in patients having ST-T changes (n = 11) it was 13.1 +/-
      10.2 (P < 0.001). For both groups <?(QRS)> was smaller than <?(ST)>, which in
      turn was smaller than <?(T)>. The values of <?(QRS)>, <?(ST)>, and <?(T)> for the
      NS, patients without and with ST-T changes were: 26.8 +/- 28.6, 42.6 +/- 41.8,
      44.9 +/- 36.5; 19.6 +/- 20.8, 26.4 +/- 31.4, 38.7 +/- 27.3; 51.0 +/- 30.0, 71.0
      +/- 36.8, 75.1 +/- 20.9, respectively (P < 0.05 for all comparisons of patients
      with versus without ST-T changes). This study showed that Dp stress, with or
      without hypoperfusion, had a clear effect on myocyte electrophysiology, expressed
      by consistent ECG amplitude changes, detected by the EVC method. The EVC method
      did not distinguish between NS and patients in this clinical setting.

PMID- 21969224
TI  - Varied types of intracranial hydatid cysts: radiological features and management
      techniques.
AB  - BACKGROUND: Even when radiological images are considered pathognomic for
      intracranial hydatid cysts, subtle image characteristics are evident depending
      upon the status/types of hydatid cysts. These imaging features, if finely
      scrutinized, may help to modify conventional surgical techniques of cyst
      excision. METHODS: From January 2006 to December 2011, nine patients (male:female
      7:2, age range 4-44 years, median 7 years) harbouring intracranial hydatid cysts
      were managed at our centre. In addition to CT scans, all patients underwent plain
      and contrast-enhanced MRI scans. Based on these radiological findings, the types
      of hydatid cysts were characterized into simple or complicated (infected) cysts.
      Complicated cysts were further differentiated into ruptured or intact subtypes
      based on imaging features. Surgical procedures including the Dowling water
      dissection technique, in addition to head rotation, were performed for removing
      these cysts intact. RESULTS: Children (n = 4) aged 6 years or less presented with
      increasing head size as the only complaint, while the rest of the patients (n =
      5) had symptoms of raised intracranial pressure. MRI features of hypo-intensity
      on T1-weighted images, hyper-intensity on T2-weighted images, and non-contrast
      enhancing cysts were noted for all simple cysts (n = 7), while iso- to mixed
      intensity on T1-weighted images and hyper-intensity on T2-weighted images with
      contrast-enhancing pericyst correctly diagnosed all complicated (infected)
      hydatid cysts (n = 2). One of these complicated cysts had spilled the infected
      contents outside the cyst wall, but within the confines of the cerebral
      parenchyma (pericyst). Such a case of contained spontaneously ruptured
      complicated hydatid cyst is described for the first time. At a median follow-up
      of 18 months, all patients remain free from cyst recurrence. CONCLUSION: Subtle
      changes in radiological features of CNS hydatid cysts should be appreciated so as
      to diagnose the type of cyst correctly. The surgical strategy should be tailored
      according to the type of cyst for favourable outcome.

PMID- 21969225
TI  - Microsurgical anatomy of membranous layers of the pituitary gland and the
      expression of extracellular matrix collagenous proteins.
AB  - BACKGROUND: There are several reports about the microanatomical and histological
      features of sellar and parasellar membranous structures and clinical studies
      about MMP proteinase as a predictive factor. However, studies on collagen
      contents of sellar and parasellar membranous structures are limited. We
      demonstrated the membranous structures surrounding the pituitary gland and
      defined extracellular matrix (ECM) collagenous proteins, collagen I-IV expression
      patterns of sellar and parasellar connective tissues. METHODS: The study was
      carried out on ten fresh postmortem human bodies at the Forensic Medicine
      Institution. Cavernous sinuses were resected with sellar structures and were
      stored at -80 degrees C liquid nitrogen tanks. Medial wall of the cavernous
      sinus, pituitary capsule and pituitary tissue samples were obtained for RT-PCR.
      Opposite side specimens were used for histological and immune staining studies.
      Collagens I-IV were studied by immunohistochemical and reverse transcription
      polymerase chain reaction (RT-PCR) methods. FINDINGS: The pituitary capsule and
      medial wall were identified as two different structures. The fibrous membrane, as
      the third membrane, was identified as staying whole in eight of ten specimens.
      Increased type IV collagen was determined in the pituitary gland, medial wall and
      pituitary capsule, respectively, in both RT-PCR and immunhistochemical studies.
      Immunhistochemical studies revealed that collagen I was strongly expressed in
      both the medial wall and pituitary gland. CONCLUSION: Increased type IV collagen
      was detected especially in pituitary tissue, the medial wall and the pituitary
      capsule by immune staining and RT-PCR. Type IV collagen was considered to be an
      important factor in the progression of adenoma and invasion.

PMID- 21969226
TI  - Effects of parental soothing behavior on stress levels of 2-8 year old children
      during voiding cystourethrograms by phase of procedure.
AB  - Using the example of a voiding cystourethrogram (VCUG), a painful radiological
      procedure, this study investigated whether parental soothing behavior (reassuring
      comments like "it's almost over" or "You're O.K." and soothing by "sh, sh") in
      one phase of the procedure influenced the child's distress in the following
      phase. The sample was comprised of 68 2-8 year-old children and the accompanying
      parent(s). Child and parental behavior during the VCUG was coded using a
      standardized rating scale (CAMPIS-R). Parental reassurance during the
      anticipatory phase significantly increased the child's distress of the following
      phase, while parental "sh, sh" significantly reduced it. Both parental behaviors
      showed no significant effect on the child's distress of the following phase when
      applied during the procedure itself. Results underline the importance of
      differentiating between anticipatory and procedural phases of the VCUG.
      Counselling methods for parents on more appropriate strategies to assist their
      children during procedural phases of the VCUG are necessary.

PMID- 21969227
TI  - No differences in the pharmacodynamics and pharmacokinetics of the thrombin
      receptor antagonist vorapaxar between healthy Japanese and Caucasian subjects.
AB  - BACKGROUND: Vorapaxar, a novel antiplatelet agent in advanced clinical
      development for the prevention and treatment of atherothrombotic disease, is a
      potent, orally bioavailable thrombin receptor antagonist selective for the
      protease-activated receptor 1 (PAR-1). METHODS: Since race/ethnicity may affect
      the safety, efficacy and dosage of drugs, this study was conducted to evaluate
      potential differences in the pharmacodynamics, pharmacokinetics and safety of
      vorapaxar after single (5, 10, 20, or 40 mg) or multiple (0.5, 1, or 2.5 mg once
      daily) doses in healthy Japanese and matched (gender, age, height, and weight)
      Caucasian volunteers. RESULTS: Vorapaxar was well tolerated in both Japanese and
      Caucasian subjects. Pharmacodynamic and pharmacokinetic profiles of vorapaxar in
      the two racial/ethnic groups were similar. In both racial groups, complete
      inhibition of platelet aggregation was achieved most rapidly with vorapaxar 40 mg
      and was consistently achieved and maintained with a 2.5 mg daily maintenance
      dose. CONCLUSION: There were no substantial differences in the safety,
      pharmacokinetics or pharmacodynamics of vorapaxar between Japanese and Caucasian
      subjects.

PMID- 21969228
TI  - Significance of trough monitoring for tacrolimus blood concentration and
      calcineurin activity in adult patients undergoing primary living-donor liver
      transplantation.
AB  - PURPOSE: Tacrolimus pharmacokinetics and calcineurin activity in peripheral blood
      mononuclear cells (PBMCs) were investigated in adult patients undergoing primary
      living-donor liver transplantation (LDLT) in order to clarify the significance of
      monitoring the tacrolimus blood trough concentration during the early post
      transplantation period. METHODS: Fourteen patients were enrolled in this study,
      and time-course data following the oral administration of a conventional
      tacrolimus formulation twice daily were obtained at 1 and 3 weeks post
      transplantation. The concentration of tacrolimus in whole blood and calcineurin
      activity in PBMCs were measured. RESULTS: The apparent clearance of tacrolimus
      significantly increased at 3 weeks versus 1 week post-transplantation, although
      the trough concentration did not significantly differ at these time points. The
      concentration at each sampling time, except at 1 h post-dose, correlated well
      with the area under the concentration-time curve from 0 to 12 h (AUC(0-12)).
      Neither the concentration at the trough time point nor AUC(0-12) was correlated
      with the area under the calcineurin activity-time curve from 0 to 12 h; however,
      calcineurin activity at the trough time point was strongly correlated with the
      latter (r (2) > 0.92). CONCLUSIONS: Based on these results, trough concentration
      monitoring can be considered an appropriate procedure for routine tacrolimus
      dosage adjustment in adult LDLT patients. Monitoring of calcineurin activity at
      the trough time point was also found to be potentially useful for predicting the
      immunological status of the patient during the tacrolimus dosing interval.

PMID- 21969229
TI  - [Inpatient and outpatient treatment in a crisis service: who uses what?].
AB  - OBJECTIVE: The aim of our study was to identify person related factors for the
      utilization of inpatient and outpatient treatment in a crisis intervention unit.
      METHODS: Data from the central psychiatric patient record (PSYREC) of the canton
      of Zurich have been analyzed. RESULTS: Different factors are associated with the
      treatment modalities. The decisive factor for the choice of an outpatient
      treatment is employment. CONCLUSIONS: The facilitation of employment should be of
      major interest for treatment in social psychiatry, e. g. by supported employment
      methods.

PMID- 21969230
TI  - [Geropsychiatric liaisonservices and nursing homes--do they need them? Results of
      a pilot study in five nursing homes in Germany].
AB  - OBJECTIVES: This project evaluates whether a multidisciplinary consultation
      liaison team with special geropsychiatric experience can help to reduce complex
      care problems in mentally ill nursing-home residents. METHODS: Prospective
      longitudinal study of patients living in 5 nursing homes in Germany, supplemented
      by expert interviews with the members of the consultation-liaison team, as well
      as semi-structured interviews and by a questionnaire answered by the
      participating nursing home staff. RESULTS: Data show that in spite of the high
      burden of disease and the usually progressive course of illness a majority of
      residents could benefit from the interventions applied by the multidisciplinary
      team. Additionally, there were positive effects on the work situation of staff
      and a reduction of costs. DISCUSSION: Our results indicate that a geropsychiatric
      consultation-liaison team for nursing homes may improve service delivery
      especially with regard to behavioral psychological symptoms in dementia (BPSD).

PMID- 21969231
TI  - [How do general practitioners deal with patients they do not consider to be
      depressed but who are classified as such according the PHQ-9?].
AB  - OBJECTIVES How GPs describe their patients who they did not identify as suffering
      from depression but who were classified as such by PHQ-9? What conclusions can be
      drawn with regard to how depression is dealt with and the illness model in use? 
      METHOD GPs who took part in a screening study were asked in interviews to talk
      about some of their patients - not being informed that these were those not
      identified as depressive by them. This study comprises 21 narrative interviews
      from 18 GPs. Analysis by Framework method by Lewis and Ritchie.  RESULTS The low
      identification rate of depression is not the result of failed recognition of
      "psychological problems" but of other factors centring on GPs' particular way of
      working and their concepts about mental illness: making a diagnosis only in a
      contextual way of interpreting symptoms; using the time passing as a help for
      diagnosing; emphasis on the impairment rather the diagnosis; considering the
      therapeutic consequences before making a diagnosis; a tolerance concerning
      "deviation" respectively wider view on "normality".  CONCLUSION Understanding the
      different ways of conceptionalizing mental illness by psychiatrists and general
      practitioners is basic for their cooperation.

PMID- 21969232
TI  - Reconsidering the heritability of intelligence in adulthood: taking assortative
      mating and cultural transmission into account.
AB  - Heritability estimates of general intelligence in adulthood generally range from
      75 to 85%, with all heritability due to additive genetic influences, while
      genetic dominance and shared environmental factors are absent, or too small to be
      detected. These estimates are derived from studies based on the classical twin
      design and are based on the assumption of random mating. Yet, considerable
      positive assortative mating has been reported for general intelligence. Unmodeled
      assortative mating may lead to biased estimates of the relative magnitude of
      genetic and environmental factors. To investigate the effects of assortative
      mating on the estimates of the variance components of intelligence, we employed
      an extended twin-family design. Psychometric IQ data were available for adult
      monozygotic and dizygotic twins, their siblings, the partners of the twins and
      siblings, and either the parents or the adult offspring of the twins and siblings
      (N = 1314). Two underlying processes of assortment were considered: phenotypic
      assortment and social homogamy. The phenotypic assortment model was slightly
      preferred over the social homogamy model, suggesting that assortment for
      intelligence is mostly due to a selection of mates on similarity in intelligence.
      Under the preferred phenotypic assortment model, the variance of intelligence in
      adulthood was not only due to non-shared environmental (18%) and additive genetic
      factors (44%) but also to non-additive genetic factors (27%) and phenotypic
      assortment (11%).This non-additive nature of genetic influences on intelligence
      needs to be accommodated in future GWAS studies for intelligence.

PMID- 21969233
TI  - Anomalous Hall effect and electron transport in ferromagnetic MnBi films.
AB  - The electron transport properties of highly c-axis oriented MnBi thin films of
      various thicknesses have been investigated. Samples are metallic but the low
      temperature resistivity shows an unusual T(3) dependence. Transverse Hall effect
      measurements show that both the ordinary and anomalous Hall coefficients decrease
      with decreasing temperature below 300 K, but the ordinary Hall coefficient (R(0))
      undergoes a sign reversal around 105 K, where the magnetic anisotropy also
      changes sign. Analysis of the Hall data for various samples shows that the
      anomalous Hall coefficient (R(s)) exhibits a strong rho(2) dependence, where rho
      is the longitudinal resistivity.

PMID- 21969234
TI  - Percutaneous ultrasound-guided thrombin injection of a post-traumatic pancreatic
      pseudoaneurysm in a pediatric patient.
AB  - Non-operative management for blunt injuries to the proximal pancreas has become
      increasingly common. A bleeding pseudoaneurysm in the setting of a traumatic
      pancreatic pseudocyst presents a morbid operation. We present the case of a 15
      year old with a grade V pancreatic injury that developed a bleeding
      pseudoaneurysm successfully treated with percutaneous ultrasound-guided thrombin
      injection.

PMID- 21969235
TI  - Intussusception as a presenting feature of Burkitt lymphoma: implications for
      management and outcome.
AB  - PURPOSE: Intussusception is a recognised but unusual presenting feature of
      Burkitt lymphoma. We sought to identify the clinical features associated with
      intussusception in this setting, and assess the outcome following protocol
      directed chemotherapy. METHODS: A retrospective case note review was performed on
      patients treated for Burkitt lymphoma at our institution between 1976 and 2010.
      Cases presenting with intussusception were identified from hospital records and
      oncology database. RESULTS: Fourteen of the 210 children seen with a diagnosis of
      Burkitt lymphoma during the study period (6.7%) developed intussusception. Median
      age was 6.1 years (range 2.5-10.9). Twelve patients presented with recurrent
      abdominal pain, and two patients with a jaw mass associated with endemic Burkitt
      lymphoma. Nine patients underwent a right hemicolectomy with ileo-colic
      anastomosis, and five had segmental small-bowel resections. Three patients had
      bone marrow involvement at diagnosis, two of whom died. All patients received
      chemotherapy. Median follow-up was 6.07 years (range 0.1-28.8). CONCLUSIONS:
      Small bowel lymphoma should be considered in children presenting with
      intussusception above the normal infantile peak age range. The presentation is
      often insidious, and complete obstruction may not be apparent. However, when
      surgically resected, the majority can achieve a good outcome with additional
      chemotherapy.

PMID- 21969236
TI  - Decrease in CD8+ lymphocyte number and altered cytokine profile in human prostate
      cancer.
AB  - The tumor microenvironment is comprised of multiple cell types arranged in a
      three-dimensional structure. Interactions amongst the various cell components
      play an important role in neoplasia, including the inflammatory reaction that
      occurs as part of the host response. In this study, the regional lymphocyte
      subpopulations and cytokine profiles associated with prostate cancer were
      examined using a quantitative imaging approach and expression microarray
      analysis. Lymphocytes were measured in four different epithelial phenotypes in
      prostate cancer specimens: carcinoma; prostatic intraepithelial neoplasia (PIN);
      benign prostate hyperplasia (BPH); and normal epithelium. The data indicate that
      CD8 positive, cytotoxic T lymphocytes are significantly decreased in regions
      adjacent to hyperplasia and carcinoma as compared to normal epithelium and PIN.
      In contrast the relative number of CD4 positive and CD20 positive lymphocytes did
      not change markedly. Parallel mRNA expression array analysis of the normal and
      tumor microenvironments identified a distinct cytokine profile in cancer, with 24
      dysregulated genes in tumor epithelium and nine altered in tumor-associated
      stroma. Overall, these data indicate that the spatial distribution of CD8
      positive, cytotoxic T lymphocytes is dysregulated in human prostate glands that
      contain cancer, and cytokine profiles are altered at the mRNA level.

PMID- 21969238
TI  - Tau protein: a possible prognostic factor in optic neuritis and multiple
      sclerosis.
AB  - BACKGROUND: Tau protein has been proposed as biomarker of axonal damage leading
      to irreversible neurological impairment in MS. CSF concentrations may be useful
      when determining risk of progression from ON to MS. OBJECTIVE: To investigate the
      association between tau protein concentration and 14-3-3 protein in the
      cerebrospinal fluid (CSF) of patients with monosymptomatic optic neuritis (ON)
      versus patients with monosymptomatic onset who progressed to multiple sclerosis
      (MS). To evaluate results against data found in a complete literature review.
      METHODS: A total of 66 patients with MS and/or ON from the Department of
      Neurology of Glostrup Hospital, University of Copenhagen, Denmark, were included.
      CSF samples were analysed for tau protein and 14-3-3 protein, and clinical and
      paraclinical information was obtained from medical records. RESULTS: The study
      shows a significantly increased concentration of tau protein in CSF from patients
      with relapsing-remitting MS and patients monosymptomatic at onset who progressed
      to MS, but interestingly no increased tau protein concentration in
      monosymptomatic ON. The concentration of tau protein was significantly correlated
      to Expanded Disability Status Scale score. No 14-3-3 protein was detected in any
      CSF sample. CONCLUSIONS: The results of this study invite further exploration of
      the possible role of tau protein as a prognostic factor to predict progression
      from ON to MS in future studies.

PMID- 21969237
TI  - Autophagy regulation in cancer development and therapy.
AB  - Autophagy is a cellular process to degrade long-lived or malfunctioning proteins
      and obsolete or damaged organelles. It maintains cellular homeostasis and helps
      cells survive stressful conditions. Tumor suppressors mostly positively regulate
      autophagy, whereas oncogene products usually inhibit autophagy. Alterations in
      key autophagy genes have also been shown to affect cancer development. However,
      the role of autophagy in cancer depends on the status of the cells and can either
      suppress or promote tumor growth. In the present review, we report on the current
      state of knowledge about the reciprocal regulation of autophagy and the potential
      role of autophagy played in cancer development and therapy.

PMID- 21969239
TI  - Effect of time of day on walking capacity and self-reported fatigue in persons
      with multiple sclerosis: a multi-center trial.
AB  - BACKGROUND: Many persons with multiple sclerosis (PwMS) report increased fatigue
      in the afternoon and evening compared with the morning. It is commonly accepted
      that physical capacity also decreases as time of day progresses, potentially
      influencing the outcomes of testing. OBJECTIVE: The objective of this article was
      to determine whether self-reported fatigue level and walking capacity are
      influenced by time of day in PwMS. METHODS: A total of 102 PwMS from 8 centers in
      5 countries, with a diverse level of ambulatory dysfunction (Expanded Disability
      Status Scale [EDSS] <6.5), participated. Patients performed walking capacity
      tests and reported fatigue level at three different time points (morning, noon,
      afternoon) during 1 day. Walking capacity was measured with the 6-Minute Walk
      Test (6MWT) and the 10-m walk test performed at usual and fastest speed. Self
      reported fatigue was measured by the Rochester Fatigue Diary (RFD). Subgroups
      with mild (EDSS 1.5-4.0, n = 53) and moderate (EDSS 4.5-6.5, n = 49) ambulatory
      dysfunction were formed, as changes during the day were hypothesized to depend on
      disability status. RESULTS: Subgroups had different degree of ambulatory
      dysfunction (p < 0.001) but reported similar fatigue levels. Although RFD scores
      were affected by time of day with significant differences between morning and
      noon/afternoon (p < 0.0001), no changes in walking capacity were found in any
      subgroup. Additional analyses on subgroups distinguished by diurnal change in
      self-reported fatigue failed to reveal analogous changes in walking capacity.
      CONCLUSIONS: Testing of walking capacity is unaffected by time of day, despite
      changes in subjective fatigue.

PMID- 21969240
TI  - Cytological and molecular characterization of Vicia barbazitae Ten. & Guss.
AB  - Vicia barbazitae, a taxon belonging to section Vicia of subgenus Vicia, was
      recovered and analysed by cytological, karyological and molecular methods with
      the aim of both proposing a general characterisation of this species and studying
      the relationships among the species of section Vicia . Phylogenetic relationships
      among the species of the section Vicia and those of the sections Microcarinae,
      Wiggersia and Atossa were also analysed. Automated karyotype analysis has been
      determined after Feulgen's reaction; chromosome banding was performed by sequence
      specific fluorochrome staining. Fluorescent chromosome banding showed
      CMA(+)/DAPI(-) NOR-associated heterochromatin in the satellite pair.
      Karyomorphological parameters, based on symmetry indices, the dendrogram of
      linkage distance constructed on 37 chromosome parameters, as well as the
      molecular data based on internal transcribed spacer sequences provided
      information about phylogenetic position of this species inside the section Vicia
      and among the species belonging to the sections Microcarinae, Wiggersia, Atossa
      and Vicia. From our karyological and molecular results, it emerges that V.
      barbazitae can be considered a natural member of section Vicia.

PMID- 21969241
TI  - Early recurrent hemorrhage after coil embolization in ruptured intracranial
      aneurysms.
AB  - INTRODUCTION: The authors present a series of patients in whom early rebleeding
      occurred after coiling for ruptured aneurysms. We investigated the incidence and
      possible mechanisms of early rebleeding. METHODS: This study consisted of 1,167
      consecutive patients who underwent coiling for a ruptured saccular aneurysm.
      Clinical and radiological data were collected retrospectively from three
      institutions. Early rebleeding was defined as occurrence of further bleeding
      within 30 days after coiling with worsening of the patient's condition. We
      divided early rebleeding into hyperacute, subacute, and delay groups depending on
      the timing of rebleeding after coil embolization. RESULTS: Incidence of early
      rebleeding after coiling of a ruptured saccular aneurysm was 1.1% (13 of 1,167),
      and mortality was 31% (4 of 13) in our series. Out of ten patients in hyperacute
      group, three (30%) had incomplete occlusion result and six patients (60%)
      underwent intra-arterial (IA) infusion of abciximab or tirofiban during the
      procedures. Seven patients (70%) had an intracerebral hemorrhage (ICH) on initial
      computed tomography. Four patients died, another four sustained severe
      disabilities, and the others had good recovery. All three patients in subacute
      and delay group showed recanalization on post-rebleeding angiography and made an
      excellent recovery. CONCLUSION: Early rebleeding was associated with high
      mortality and morbidity. IA abciximab infusion or thrombolytic interventions
      during the procedure, maintenance of anticoagulation after the procedure,
      incomplete treatment of the aneurysms, and presence of ICH seemed to be related
      to hyperacute early rebleeding after coiling. Increased aneurysmal size and coil
      compaction could induce subacute and delayed early rebleeding.

PMID- 21969242
TI  - Angiographic CT with intravenous contrast agent application for monitoring of
      intracranial flow diverting stents.
AB  - INTRODUCTION: Intracranial flow diverting devices are increasingly used to treat
      cerebral aneurysms. A reliable, non-invasive follow-up modality would be
      desirable. Our aim was to compare intra-arterial digital subtraction angiography
      (ia DSA) to angiographic computed tomography with intravenous contrast agent
      application (iv ACT) in the visualisation of flow diverting devices and aneurysm
      lumina. METHODS: Follow-up monitoring by iv ACT (n = 36) and ia DSA (n = 25) in
      14 patients treated with flow diverting devices for intracranial aneurysms was
      evaluated retrospectively. Images were evaluated by two neuroradiologists in
      anonymous consensus reading regarding the device deployment, wall apposition,
      neck coverage of the aneurysm, opacification of the vessel and device lumen, as
      well as the degree of aneurysm occlusion. RESULTS: Corresponding ia DSA and iv
      ACT images were scored identically in all patients regarding the stent
      deployment, wall apposition and neck coverage, as well as the degree of aneurysm
      occlusion and patency status of the device and parent artery. Opacification of
      the parent vessel lumen and perfused parts of the aneurysm was considered
      slightly inferior for iv ACT in comparison with ia DSA (seven of 36 cases),
      without impact on diagnosis. CONCLUSIONS: We demonstrated the feasibility and
      diagnostic value of iv ACT in follow-up imaging of intracranial flow diverting
      devices. Due to its high spatial resolution and non-invasive character, this
      novel technique might become a valuable imaging modality in these patients.

PMID- 21969244
TI  - Floating elementary osmotic pump tablet (FEOPT) for controlled delivery of
      diethylcarbamazine citrate: a water-soluble drug.
AB  - The present work investigates the feasibility of the design of a novel floating
      elementary osmotic pump tablet (FEOPT) to prolong the gastric residence of a
      highly water-soluble drug. Diethylcarbamazine citrate (DEC) was chosen as a model
      drug. The FEOPT consisted of an osmotic core (DEC, mannitol, and hydrophilic
      polymers) coated with a semipermeable layer (cellulose acetate) and a gas
      generating gelling layer (sodium bicarbonate, hydrophilic polymers) followed by a
      polymeric film (Eudragit RL 30D). The effect of formulation variables such as
      concentration of polymers, types of diluent, and coat thickness of semipermeable
      membrane was evaluated in terms of physical parameters, floating lag time,
      duration of floatation, and in vitro drug release. The Fourier transform infrared
      and X-ray diffraction analysis were carried out to study the physicochemical
      changes in the drug excipients powder blend. The integrity of the orifice and
      polymeric film layer was confirmed from scanning electron microscopy image. All
      the developed FEOPT showed floating lag time of less than 8 min and floating
      duration of 24 h. A zero-order drug release could be attained for DEC. The
      formulations were found to be stable up to 3 months of stability testing at 40
      degrees C/75% relative humidity.

PMID- 21969243
TI  - Effects of Lens culinaris agglutinin on gene expression of gluconeogenic enzymes
      in the mouse intestine.
AB  - BACKGROUND: Lectins are proteins that bind specifically to the carbohydrate
      moiety of glyco-conjugates. Japanese mistletoe lectin given intragastrically
      affected cytokine gene expression in the mouse intestine. This study examines the
      actions of Lens culinaris agglutinin (LCA) on the gene expression of
      gluconeogenic enzymes in the intestine. RESULTS: The results of quantitative real
      time reverse transcription-polymerase chain reaction indicated that LCA caused an
      up-regulation of the gene expression of glucose-6-phosphatase (G6Pase) and
      phosphoenolpyruvate carboxykinase (PEPCK). This change was correlated with an
      increase in the expression of two transcription factors, HNF1alpha and HNF4alpha.
      Experiments using human colonic cancer Caco-2 cells demonstrated that LCA up
      regulated the gene expression of G6Pase and PEPCK whereas insulin had the
      opposite effect. In addition, the observed up-regulation of HNF4alpha gene
      expression in the duodenum raises the possibility that the lectin promotes the
      colorectal cancer. CONCLUSION: Lentil beans should be cooked well to avoid
      unfavourable effects of LCA.

PMID- 21969245
TI  - De-risking pharmaceutical tablet manufacture through process understanding,
      latent variable modeling, and optimization technologies.
AB  - In pharmaceutical tablet manufacturing processes, a major source of disturbance
      affecting drug product quality is the (lot-to-lot) variability of the incoming
      raw materials. A novel modeling and process optimization strategy that
      compensates for raw material variability is presented. The approach involves
      building partial least squares models that combine raw material attributes and
      tablet process parameters and relate these to final tablet attributes. The
      resulting models are used in an optimization framework to then find optimal
      process parameters which can satisfy all the desired requirements for the final
      tablet attributes, subject to the incoming raw material lots. In order to de-risk
      the potential (lot-to-lot) variability of raw materials on the drug product
      quality, the effect of raw material lot variability on the final tablet
      attributes was investigated using a raw material database containing a large
      number of lots. In this way, the raw material variability, optimal process
      parameter space and tablet attributes are correlated with each other and offer
      the opportunity of simulating a variety of changes in silico without actually
      performing experiments. The connectivity obtained between the three sources of
      variability (materials, parameters, attributes) can be considered a design space
      consistent with Quality by Design principles, which is defined by the ICH-Q8
      guidance (USDA 2006). The effectiveness of the methodologies is illustrated
      through a common industrial tablet manufacturing case study.

PMID- 21969248
TI  - Esophageal achalasia 2011: pneumatic dilatation or laparoscopic myotomy?
AB  - This article reviews the changes that have taken place in the treatment of
      patients with achalasia in the last 20 years. It compares and contrasts treatment
      preferences in the USA with those of Canada and Europe. It provides a critical
      analysis of the recent randomized trial between laparoscopic Heller myotomy and
      pneumatic dilatation that was carried out in several European centers. It
      supports the use of laparoscopic Heller myotomy as the preferred treatment for
      the average patient with this disease in the USA.

PMID- 21969249
TI  - Exercise-associated hyponatremia in the tropics.

PMID- 21969251
TI  - The relationship between structurally different pyrrolizidine alkaloids and
      western flower thrips resistance in F(2) hybrids of Jacobaea vulgaris and
      Jacobaea aquatica.
AB  - Segregating plant hybrids often have more ecological and molecular variability
      compared to parental species, and are therefore useful for studying relationships
      between different traits, and the adaptive significance of trait variation.
      Hybrid systems have been used to study the relationship between the expression of
      plant defense compounds and herbivore susceptibility. We conducted a western
      flower thrips (WFT) bioassay using a hybrid family and investigated the
      relationship between WFT resistance and pyrrolizidine alkaloid (PA) variation.
      The hybrid family consisted of two parental (Jacobaea vulgaris and Jacobaea
      aquatica) genotypes, two F(1) genotypes, and 94 F(2) hybrid lines. The J.
      aquatica genotype was more susceptible to thrips attack than the J. vulgaris
      genotype, the two F(1) hybrids were as susceptible as J. aquatica, and
      susceptibility to WFT differed among F(2) hybrid lines: 69 F(2) lines were
      equally susceptible compared to J. aquatica, 10 F(2) lines were more susceptible
      than J. aquatica and 15 F(2) lines were as resistant as J. vulgaris or were
      intermediate to the two parental genotypes. Among 37 individual PAs that were
      derived from four structural groups (senecionine-, jacobine-, erucifoline- and
      otosenine-like PAs), the N-oxides of jacobine, jaconine, and jacoline were
      negatively correlated with feeding damage caused by WFT, and the tertiary amines
      of jacobine, jaconine, jacoline, and other PAs did not relate to feeding damage.
      Total PA concentration was negatively correlated with feeding damage. Among the
      four PA groups, only the total concentration of the jacobine-like PAs was
      negatively correlated with feeding damage. Multiple regression tests suggested
      that jacobine-like PAs play a greater role in WFT resistance than PAs from other
      structural groups. We found no evidence for synergistic effects of different PAs
      on WFT resistance. The relationship between PA variation and WFT feeding damage
      in the Jacobaea hybrids suggests a role for PAs in resistance to generalist
      insects.

PMID- 21969252
TI  - Comments on 'Choosing an optimal method to combine p-values' by Sungho Won,
      Nathan Morris, Qing Lu and Robert C. Elston, Statistics in Medicine 2009; 28:1537
      1553.

PMID- 21969254
TI  - Comments on 'Sequential methods for random-effects meta-analysis' by J. P.
      Higgins, A. Whitehead and M. Simmonds, Statistics in Medicine 2010; DOI:
      10.1002/sim.4088.

PMID- 21969255
TI  - Deterministic and non-deterministic switching in chains of magnetic hysterons.
AB  - This paper presents a fundamental analysis of a single-domain ferromagnetic
      particles chain hysteresis in perpendicular geometry as a prototype for ultra
      high density memories. Due to magnetostatic long range interactions the system
      has a complex hysteresis but stable features can be found. The loop has a number
      of deterministic Barkhausen jumps and consequently a number of stable plateaus
      that could be used in multistate memories. The fundamental elements that sustain
      this behavior are shown and discussed.

PMID- 21969256
TI  - Prognostic value of mild-to-moderate pulmonary hypertension in patients with
      severe aortic valve stenosis undergoing aortic valve replacement.
AB  - BACKGROUND: Optimal timing of elective aortic valve replacement (AVR) for severe
      aortic stenosis (AS) is challenging. Hence, a sensitive marker in AS patients
      indicating increasing risk after AVR would be of great clinical value. In the
      present study, we hypothesized that mild-to-moderate pulmonary hypertension (PH)
      assessed prior to AVR is a sensitive marker for adverse events in patients after
      successful AVR. METHODS: We enrolled 200 consecutive patients with severe AS
      undergoing AVR. Among them, 176 patients (88%) were symptomatic. Patients were
      divided according to systolic pulmonary artery pressure (PAP(sys)) into three
      groups: no PH (PAP(sys) <30 mmHg), mild-to-moderate PH (PAP(sys) >=30 and
      PAP(sys) <60 mmHg) and severe PH (>=60 mmHg). Multivariable analyses were
      adjusted for age and gender and included PH, left ventricular ejection fraction
      <=35%, renal insufficiency and logistic EuroSCORE >=20%. Primary endpoint was
      death of any cause within 5 years after AVR. RESULTS: During follow-up, 23
      patients died (cumulative 5-year mortality rate 14.6%). Patients without (n =
      78), mild-to-moderate (n = 99) and severe PH (n = 23) had 5-year mortality rates
      of 2.6, 15.2 and 26.1% (p = 0.001). PAPsys >=30 mmHg yielded an excellent level
      of sensitivity of 92.8%. On multivariable analysis, mild-to-moderate PH was the
      only independent risk factor (hazard ratio 4.9, 95% confidence interval 1.1
      21.8). CONCLUSIONS: In patients with severe AS undergoing AVR, mild-to-moderate
      PH is a strong and independent predictor of late mortality. Conversely, patients
      with normal PAP(sys) have an extremely good prognosis.

PMID- 21969257
TI  - Prolyl 4-hydroxylase genes are subjected to alternative splicing in roots of
      maize seedlings under waterlogging.
AB  - BACKGROUND: In animals, prolyl 4-hydroxylases (P4Hs) are regarded as oxygen
      sensors under hypoxia stress, but little is known about their role in the
      response to waterlogging in maize. METHODS: A comprehensive genome-wide analysis
      of P4H genes of maize (zmP4H genes) was carried out, including gene structures,
      phylogeny, protein motifs, chromosomal locations and expression patterns under
      waterlogging. KEY RESULTS: Nine zmP4H genes were identified in maize, of which
      five were alternatively spliced into at least 19 transcripts. Different
      alternative splicing (AS) events were revealed in different inbred lines, even
      for the same gene, possibly because of organ and developmental specificities or
      different stresses. The signal strength of splice sites was strongly correlated
      with selection of donor and receptor sites, and ambiguous junction sites due to
      small direct repeats at the exon/intron junction frequently resulted in the
      selection of unconventional splicing sites. Eleven out of 14 transcripts
      resulting from AS harboured a premature termination codon, rendering them
      potential candidates for nonsense-mediated RNA degradation. Reverse transcription
      PCR (RT-PCR) indicated that zmP4H genes displayed different expression patterns
      under waterlogging. The diverse transcripts generated from AS were expressed at
      different levels, suggesting that zmP4H genes were under specific control by post
      transcriptional regulation under waterlogging stress in the line HZ32.
      CONCLUSIONS: Our results provide a framework for future dissection of the
      function of the emerging zmP4H family and suggest that AS might have an important
      role in the regulation of the expression profile of this gene family under
      waterlogging stress.

PMID- 21969259
TI  - Launching of American Journal of Cancer Research.

PMID- 21969258
TI  - Development and persistence of sandsheaths of Lyginia barbata (Restionaceae):
      relation to root structural development and longevity.
AB  - BACKGROUND AND AIMS: Strongly coherent sandsheaths that envelop perennial roots
      of many monocotyledonous species of arid environments have been described for
      over a century. This study, for the first time, details the roles played by the
      structural development of the subtending roots in the formation and persistence
      of the sheaths. METHODS: The structural development of root tissues associated
      with persistent sandsheaths was studied in Lyginia barbata, native to the Western
      Australian sand plains. Cryo-scanning electron microscopy CSEM, optical
      microscopy and specific staining methods were applied to fresh, field material.
      The role of root hairs was clarified by monitoring sheath development in roots
      separated from the sand profile by fine mesh. KEY RESULTS AND CONCLUSIONS: The
      formation of the sheaths depends entirely on the numerous living root hairs which
      extend into the sand and track closely around individual grains enmeshing, by
      approx. 12 cm from the root tip, a volume of sand more than 14 times that of the
      subtending root. The longevity of the perennial sheaths depends on the subsequent
      development of the root hairs and of the epidermis and cortex. Before dying, the
      root hairs develop cellulosic walls approx. 3 um thick, incrusted with ferulic
      acid and lignin, which persist for the life of the sheath. The dead hairs remain
      in place fused to a persistent platform of sclerified epidermis and outer cortex.
      The mature cortex comprises this platform, a wide, sclerified inner rim and a
      lysigenous central region - all dead tissue. We propose that the sandsheath/root
      hair/epidermis/cortex complex is a structural unit facilitating water and
      nutrient uptake while the tissues are alive, recycling scarce phosphorus during
      senescence, and forming, when dead, a persistent essential structure for
      maintenance of a functional stele in the perennial Lyginia roots.

PMID- 21969261
TI  - Effect of a dietary supplement containing glucosamine hydrochloride, chondroitin
      sulfate and quercetin glycosides on symptomatic knee osteoarthritis: a
      randomized, double-blind, placebo-controlled study.
AB  - BACKGROUND: Oral glucosamine and chondroitin sulfate, alone and in combination,
      have been used worldwide for the treatment of osteoarthritis (OA), but their
      efficacy is controversial. This clinical study was aimed at investigating the
      potential of a dietary supplement containing glucosamine and chondroitin sulfate
      in combination with derivatives of quercetin, a naturally occurring flavonoid,
      (GCQ supplement) for knee OA care. RESULTS: A randomized, double-blind, placebo
      controlled study was conducted in 40 Japanese subjects with symptomatic knee OA.
      Subjects were randomly assigned to GCQ supplement (1200 mg glucosamine
      hydrochloride, 60 mg chondroitin sulfate and 45 mg quercetin glycosides per day)
      or placebo and the treatment and follow-up were continued for 16 weeks. The
      results of symptomatic efficacy assessment based on Japanese Orthopaedic
      Association criteria showed that scores for two of the four symptom/function
      subscales, as well as the aggregate scores, were significantly improved at week
      16 or earlier in the GCQ group compared to the placebo group. Moreover, analyses
      of cartilage metabolism biomarkers showed a trend of improvement in type II
      collagen synthesis/degradation balance in the GCQ group during follow-up.
      CONCLUSION: GCQ supplement was thought to be more effective than placebo in
      decreasing the intensity of knee OA-associated clinical symptoms.

PMID- 21969263
TI  - One world, one woman: a kyosei approach to primary ovarian insufficiency.

PMID- 21969260
TI  - Radiation-induced tumor neoantigens: imaging and therapeutic implications.
AB  - Exposure of tumor cells to ionizing radiation (IR) is widely known to induce a
      number of cellular changes. One way that IR can affect tumor cells is through the
      development of neoantigens which are new molecules that tumor cells express at
      the cell membrane following some insult or change to the cell. There have been
      numerous reports in the literature of changes in both tumor and tumor vasculature
      cell surface molecule expression following treatment with IR. The usefulness of
      neoantigens for imaging and therapeutic applications lies in the fact that they
      are differentially expressed on the surface of irradiated tumor cells to a
      greater extent than on normal tissues. This differential expression provides a
      mechanism by which tumor cells can be "marked" by radiation for further
      targeting. Drug delivery vehicles or imaging agents conjugated to ligands that
      recognize and interact with the neoantigens can help to improve tumor-specific
      targeting and reduce systemic toxicity with cancer drugs. This article provides a
      review of the molecules that have been reported to be expressed on the surface of
      tumor cells in response to IR either in vivo or in vitro. Additionally, we
      provide a discussion of some of the methods used in the identification of these
      antigens and applications for their use in drug delivery and imaging.

PMID- 21969264
TI  - FMR1 and the continuum of primary ovarian insufficiency.
AB  - Spontaneous 46,XX primary ovarian insufficiency (POI) is a term that describes
      ovarian dysfunction resulting in a range of abnormalities, from infertility to
      early menopause as the end stage (overt POI). The most common known genetic cause
      of 46,XX POI is the expansion of a CGG repeat to 55 to 199 copies in the 5'
      untranslated region in the X-linked  FMR1 gene. This "premutation" is associated
      with overt POI (FXPOI) in ~20% of carrier women. Greater than 200 CGG copies
      results in methylation of the CGG repeats and subsequent silencing of the  FMR1
      gene, causing fragile X syndrome. This "full" mutation is not associated with
      FXPOI. Even in the absence of overt FXPOI, women who carry the premutation may
      exhibit ovarian dysfunction along a continuum of severity. Evidence also suggests
      that the severity of FXPOI depends on the CGG repeat length, background modifier
      genes, and environmental factors (e.g., smoking). This review explores the range
      of ovarian dysfunction, the mechanisms behind the dysfunction, and the reasons
      for the variability in presentation in women who carry the  FMR1 premutation.
      Understanding the mechanisms responsible for development of FXPOI is paramount to
      providing these women with the best overall health care.

PMID- 21969266
TI  - Bone health in primary ovarian insufficiency.
AB  - The etiology of primary ovarian insufficiency (POI) may be genetic, autoimmune,
      or iatrogenic. Genetic conditions include 45,X, 46,XX and 46,XY POI, and POI
      associated with galactosemia and FMR premutations. Women with autoimmune
      polyglandular syndromes 1 and 2 may develop autoimmune POI, as may those who
      receive chemotherapy or radiotherapy. Hypogonadism in POI can result in reduced
      rates of bone mass accrual in adolescents and young women, and low bone density
      for age in older women. Measures to optimize bone density in women with POI
      include attention to lifestyle measures and hormone replacement. Resistance
      training and adequate calcium and vitamin D supplementation are essential, as is
      replacement of estrogen/progestin. Estrogen/progestin replacement may be
      problematic in women with estrogen-sensitive breast cancer who developed POI in
      the course of therapy for cancer. In these instances, bisphosphonates are an
      option. In particular, zoledronic acid has been used successfully in conjunction
      with chemotherapy, tamoxifen, and aromatase inhibitors.

PMID- 21969265
TI  - Mechanisms and models of immune tolerance breakdown in the ovary.
AB  - Ovarian autoimmunity is increasingly implicated in the etiology of primary
      ovarian insufficiency (POI), previously termed  PREMATURE OVARIAN FAILURE or 
      PREMATURE MENOPAUSE. Links to autoimmunity in human POI have long been noted due
      to the close association of POI with several autoimmune diseases and syndromes
      such as Addison's disease and Autoimmune polyglandular syndrome 1. However,
      diagnosis of autoimmune-mediated POI (aPOI) remains challenging because of the
      lack of sensitive or specific markers of disease. Autoimmunity can arise from the
      breakdown of immunological tolerance in several ways. How then may we discern
      what constitutes a relevant target and what represents a downstream phenomenon?
      The answer lies in the study of pathogenic mechanisms in translational models of
      disease. From examples in humans and mice, we see that ovarian autoimmunity
      likely arises from a limited number of antigens targeted in the ovary that are
      organ specific. These antigens may be conserved but not limited to those seen in
      animal models of autoimmune ovarian disease. Recent advances in these areas have
      begun to define the relevant antigens and mechanisms of immune tolerance
      breakdown in the ovary. Work in translational models continues to provide insight
      into mechanisms of disease pathogenesis that will allow more accurate diagnosis
      and, ultimately, improved interventions for women with aPOI.

PMID- 21969267
TI  - Cardiovascular disease and primary ovarian insufficiency.
AB  - Cardiovascular disease (CVD) is the number-one killer of women. Women with
      primary ovarian insufficiency (POI) may be more burdened by cardiovascular
      disease, such as myocardial infarction and stroke, as compared with women with
      normal menopause. The increased burden may be mediated by a worsening of
      cardiovascular risk factors, such as lipids, corresponding with the loss of
      ovarian function. In contrast, the increased burden may be caused by factors that
      precede and potentially contribute to both CVD events and ovarian decline, such
      as X-chromosome abnormalities and smoking. Regardless of the cause, women with
      POI may serve as an important population to target for CVD screening and
      prevention strategies. These strategies should include the use of CVD risk
      stratification tools to identify women that may benefit from lifestyle
      modification and pharmacological therapy to prevent CVD. Sex steroid therapy for
      the sole purpose of CVD prevention in women with POI cannot be recommended, based
      on a lack of evidence.

PMID- 21969268
TI  - Turner syndrome: contemporary thoughts and reproductive issues.
AB  - Turner syndrome is a common genetic disorder that has been classically associated
      with a 45,X karyotype. Several X-chromosomal abnormalities have been identified
      in these patients, many of which involve mosaicism. These patients have variable
      but predictable phenotypic findings and are at risk for development of endocrine,
      autoimmune, and structural abnormalities. As many as 1.5% of the population with
      Turner syndrome may develop dissection and rupture of the ascending aorta; the
      presence of abnormalities of the cardiac tree and hypertension increase this
      risk, but their absence does not preclude it. Rupture has occurred at aortic
      diameters smaller than previously reported for other patient populations. Five
      percent or more of women with Turner syndrome may have abbreviated menstrual
      function before developing amenorrhea and hypergonadotropic hypogonadism. An
      estimated 1 to 2% of all patients may become pregnant. Only three patients with
      Turner syndrome (and two of them with streak ovaries) have ever been reported to
      become pregnant after developing amenorrhea and elevated gonadotropin levels.
      Pregnancy, either spontaneous or more commonly from donor oocyte, increases
      maternal mortality rate for these women by an estimated >=100 fold. It appears
      that all Turner women are at risk of rupture; neither prior spontaneous menses
      nor age >30 years provides protection. In addition, the literature suggests that
      the physiological changes of pregnancy may increase the risk of rupture in future
      years after delivery for those Turner women who seemingly made it safely through
      pregnancy. The use of the term  PRIMARY OVARIAN INSUFFICIENCY (POI) for Turner
      syndrome gives me some discomfort. For women with 46,XX hypergonadotropic
      hypogonadism, POI accurately provides the suggestion that follicular depletion is
      often not complete (although remissions are usually self-limiting and the vast
      majority of patients will not spontaneously become pregnant). I clearly
      understand the need to prevent any stigmatization to patients unfortunately
      diagnosed with premature oocyte depletion, and I believe that the use of the
      diagnosis POI leaves the door open for the occurrence of reproductive function
      and for the 5 to 10% of 46,XX patients who may spontaneously become pregnant.
      However, the world literature reports only two women with Turner syndrome,
      hypergonadotropic amenorrhea, and streak ovaries who have ever become pregnant
      spontaneously after their diagnosis. It would be unfair to such women with Turner
      syndrome to give them the same hope for pregnancy as we do for women with 46,XX
      POI. Amenorrheic women with Turner syndrome truly have ovarian failure. Although
      I have adopted the term  POI in this article for women with Turner syndrome,
      semantics are no substitute for honest, thorough, and compassionate counseling.

PMID- 21969270
TI  - Life plans and family-building options for women with primary ovarian
      insufficiency.
AB  - Primary ovarian insufficiency (POI) compromises a woman's chance of conceiving
      with her own oocytes. Although biomarkers such as serum follicle-stimulating
      hormone, serum antimullerian hormone, and assessment of antral follicle count by
      transvaginal ultrasound can give some general idea about ovarian activity and
      perhaps fertility potential, no marker will definitively predict if and when
      childbearing will be possible for women with POI. No medical therapy has yet been
      definitively proven to improve ovarian function and fertility for women with
      overt POI. Fertility preservation, with cryopreservation of ovarian tissue,
      oocytes, or embryos, can be considered for some women with POI if oocytes are
      retrievable and current childbearing is not desired, with the caveat that data
      regarding long-term safety and efficacy are not available for women with POI.
      Options with a high chance of success are oocyte donation, embryo donation, and
      adoption. Child-free living may be a reasonable choice for some women. It is
      beneficial for women with POI to hear all life-plan and family-building options
      presented in a balanced manner.

PMID- 21969269
TI  - From victim to survivor to thriver: helping women with primary ovarian
      insufficiency integrate recovery, self-management, and wellness.
AB  - Most women discover that they are infertile in a gradual manner after many failed
      attempts at conception. By contrast, most women with primary ovarian
      insufficiency (POI) uncover their infertility as part of an evaluation of other
      presenting complaints, frequently before attempts at conception have even been
      contemplated. The most common words women use to describe how they feel in the
      hours after getting the diagnosis of POI are "devastated," "shocked," and
      "confused." Clearly, the news propels some patients onto a difficult journey. POI
      is a serious and incurable chronic disease. The diagnosis is more than
      infertility and affects a woman's physical and emotional well-being. Management
      of the condition must address both. Patients face the acute shock of the
      diagnosis, associated stigma of infertility, grief from the death of dreams,
      anxiety from the disruption of life plans, confusion around the cause, symptoms
      of estrogen deficiency, worry over the associated potential medical sequelae such
      as reduced bone density and cardiovascular risk, and the uncertain future that
      all of these factors create. There is a need for an evidenced-based integrated
      program to assist women with POI in navigating the transition to acceptance of
      the diagnosis, ongoing management of the condition, and ongoing maintenance of
      wellness in the presence of the disorder. A health-centered approach can
      gradually replace the disease-centered approach and put patients in partnerships
      with professional health-care providers. Ideally, the journey transitions each
      patient from seeing herself as a victim, to a survivor, to a woman who is
      thriving.

PMID- 21969271
TI  - Deficient CCR7 signaling promotes TH2 polarization and B-cell activation in vivo.
AB  - The chemokine receptor CCR7 has a central role in regulating homing and
      positioning of T cells and DCs to lymph nodes (LNs) and participates in T-cell
      development and activation. In this study, we addressed the role of CCR7
      signaling in T(H) 2 polarization and B-cell activation. We provide evidence that
      the lack of CCR7 drives the capacity of naive CD4(+)  T cells to polarize toward
      T(H) 2 cells. This propensity contributes to a lymph node environment in CCR7
      deficent mice characterized by increased expression of IL-4 and increased
      frequency of T(H) 2 cells. We show that elevated IL-4 levels lead to B-cell
      activation characterized by up-regulated expression of MHC class II, CD23 and
      CD86. Activated B cells are in turn highly efficient in presenting antigen to
      CD4(+)  T cells and thus potentially contribute to the T(H) 2 microenvironment.
      Taken together, our results support the idea of a CCR7-dependent patterning of
      T(H) 2 responses, with absent CCR7 signaling favoring T(H) 2 polarization,
      dislocation of T helper cells into the B-cell follicles and, as a consequence, B
      cell activation.

PMID- 21969272
TI  - A Bayesian approach to risk-adjusted outcome monitoring in healthcare.
AB  - Clinical outcomes are commonly monitored in healthcare practices to detect
      changes in care providers' performance. One key challenge in outcome monitoring
      is the need of adjustment for patient base-line risks. Various control charting
      methods have been developed to conduct risk-adjusted outcome monitoring, but they
      all rely on the availability of a large number of historical data. We propose a
      Bayesian approach to this type of monitoring for cases where historical data are
      not available. In our approach, detection of change is formulated as a model
      selection problem and solved using a popular Bayesian tool for variable
      selection, the Bayes factor. Issues in decision-making about whether there is a
      change point in the observed patient outcomes are addressed, including
      specification of priors and computation of Bayes factors. This approach is
      applied to a real data set on cardiac surgeries, and its performance under
      different parameter scenarios is studied through simulations.

PMID- 21969273
TI  - Multi-level relaxation model for describing the Mossbauer spectra of single
      domain particles in the presence of quadrupolar hyperfine interaction.
AB  - A multi-level stochastic model taking into account the magnetic anisotropy,
      precession and diffusion of the uniform magnetization of single-domain particles
      is developed in order to describe the Mossbauer absorption spectra of an ensemble
      of magnetic nanoparticles in the presence of quadrupolar hyperfine interaction
      with an arbitrary orientation of its principal axes. This model allows one to
      take into account physical mechanisms for forming the hyperfine structure in a
      real situation and can be easily realized even on a personal computer. In
      particular, now one can numerically describe qualitative features of temperature
      evolution of the Mossbauer spectral shape from a 'symmetric' magnetic sextet to a
      quadrupolar doublet of lines, which has been observed in a large number of
      experimental spectra of (57)Fe nuclei in magnetic nanoparticles for almost half a
      century.

PMID- 21969274
TI  - New starch preparations resistant to enzymatic digestion.
AB  - BACKGROUND: New starch preparations were produced by thermolysis of potato starch
      in the presence of inorganic (hydrochloric) and organic (citric and tartaric)
      acids under controlled conditions. The starch preparations were physicochemically
      and structurally characterised and analysed for their resistance to enzymatic
      digestion in vitro. RESULTS: The content of resistant fraction in dextrin D1,
      obtained by heating starch acidified with hydrochloric and citric acids,
      determined by the AOAC 2001.03 and pancreatin-gravimetric methods was similar
      (~200 g kg-1). In the case of dextrin D3, obtained by heating starch acidified
      with hydrochloric and tartaric acids, the result of determination by the
      pancreatin-gravimetric method was almost four times higher than that obtained
      with the AOAC 2001.03 method. The enzymatic tests revealed that dextrin D3
      obtained with excess tartaric acid can be classified as RS4, which can only be
      partially determined by enzymatic-gravimetric methods. Tartaric acid at high
      concentration had a significantly stronger influence on starch hydrolysis than
      citric acid. This was confirmed by chromatographic analysis of dextrins and
      chemical investigation of the reducing power. CONCLUSION: The results confirmed
      the possibility of applying dextrins, prepared under specific conditions, as
      soluble dietary fibre.

PMID- 21969275
TI  - The anthrax attacks 10 years later.
AB  - Ten years ago, just weeks after the September 11 attacks, the United States
      experienced a deliberate act of bioterrorism. Through use of the postal service,
      anthrax spores were widely disseminated, including to homes, the Senate, and
      major newsrooms, resulting in morbidity and mortality and effectively disrupting
      our way of life and revealing our vulnerability. Even though such attacks had
      been the subject of much writing and had been planned for, detection of and the
      appropriate response to an attack with an agent from the so-called "Category 'A'
      List" had only been considered in theoretical terms. What transpired during the
      following difficult weeks, including how public health and federal government
      agencies performed, has been both praised and criticized. An intertwined
      epidemiologic and criminal investigation of such magnitude was unprecedented in
      U.S. history. To address the question of whether we as a nation are now better
      prepared for future threats involving biologic agents, it is important to learn
      from the lessons of the 2001 anthrax attacks, including the critical role of
      clinicians in surveillance. As physicians involved in diagnosing anthrax in the
      index case and alerting authorities, we offer our perspective on these events a
      decade after their occurrence.

PMID- 21969277
TI  - The optimal discovery procedure in multiple significance testing: an empirical
      Bayes approach.
AB  - Multiple testing has been widely adopted for genome-wide studies such as
      microarray experiments. To improve the power of multiple testing, Storey (J.
      Royal Statist. Soc. B 2007; 69: 347-368) recently developed the optimal discovery
      procedure (ODP) which maximizes the number of expected true positives for each
      fixed number of expected false positives. However, in applying the ODP, we must
      estimate the true status of each significance test (null or alternative) and the
      true probability distribution corresponding to each test. In this article, we
      derive the ODP under hierarchical, random effects models and develop an empirical
      Bayes estimation method for the derived ODP. Our methods can effectively
      circumvent the estimation problems in applying the ODP presented by Storey.
      Simulations and applications to clinical studies of leukemia and breast cancer
      demonstrated that our empirical Bayes method achieved theoretical optimality and
      performed well in comparison with existing multiple testing procedures.

PMID- 21969276
TI  - DOCK8 is essential for T-cell survival and the maintenance of CD8+ T-cell memory.
AB  - Deficiency in the guanine nucleotide exchange factor dedicator of cytokinesis 8
      (DOCK8) causes a human immunodeficiency syndrome associated with recurrent
      sinopulmonary and viral infections. We have recently identified a DOCK8-deficient
      mouse strain, carrying an ethylnitrosourea-induced splice-site mutation that
      shows a failure to mature a humoral immune response due to the loss of germinal
      centre B cells. In this study, we turned to T-cell immunity to investigate
      further the human immunodeficiency syndrome and its association with decreased
      peripheral CD4(+)  and CD8(+)  T cells. Characterisation of the DOCK8-deficient
      mouse revealed T-cell lymphopenia, with increased T-cell turnover and decreased
      survival. Egress of mature CD4(+)  thymocytes was reduced with increased
      migration of these cells to the chemokine CXCL12. However, despite the two-fold
      reduction in peripheral naive T cells, the DOCK8-deficient mice generated a
      normal primary CD8(+)  immune response and were able to survive acute influenza
      virus infection. The limiting effect of DOCK8 was in the normal survival of
      CD8(+)  memory T cells after infection. These findings help to explain why DOCK8
      deficient patients are susceptible to recurrent infections and provide new
      insights into how T-cell memory is sustained.

PMID- 21969278
TI  - The impact of etched trenches geometry and dielectric material on the electrical
      behaviour of silicon-on-insulator self-switching diodes.
AB  - Hole electrical transport in a p-doped nanochannel defined between two L-shape
      etched trenches made on a silicon-on-insulator substrate is investigated using a
      TCAD-Medici simulator. We study the impact of the etched trenches' geometry and
      dielectric filling materials on the current-voltage characteristics of the
      device. Carrier accumulation on frontiers defined by the trenches causes a
      modulation of the hole density inside the conduction channel as the bias voltage
      varies and this gives rise to a diode-like characteristic. For a 1.2 um-long
      channel, plots of the electric field distribution show that a nonlinear transport
      regime is reached at a moderate reverse and forward bias of  +/- 2 V. Plots of
      the carrier velocity along the conduction channel show that holes remain hot for
      a few hundreds of nm outside the nanometre-wide channel, at a bias of  +/- 10 V.
      Filling the etched trenches with a high-kappa  dielectric material gives rise to
      a lower threshold voltage, V(th). A similar decrease of V(th)  is also achieved
      by reducing the longitudinal and/or the transverse trench width. Our simulation
      results provide useful design guidelines for future integrated self-switching
      diode-based circuits.

PMID- 21969279
TI  - Mobile and landline telephone performance outcomes among telephone-using cochlear
      implant recipients.
AB  - OBJECTIVE: To objectively study mobile and standard landline telephone speech
      perception performance using cochlear implant recipients. STUDY DESIGN:
      Nonrandomized trial. SETTING: Tertiary referral center. SUBJECTS AND METHODS:
      Twenty-five subjects enrolled in this study from a pool of 50 cochlear implant
      recipients who had participated in an earlier questionnaire study from which
      demographic data were gathered. Preoperative speech perception scores were
      collated from preoperative audiological data. Postoperative speech perception
      scores were calculated with subjects listening to the Australian Version of the
      Bamford-Kowal-Bench Sentence Test read aloud in a soundproof booth via live
      voice, played back on a speaker, on a standard landline and mobile phone.
      Telephone speech perception scores were analyzed and banded into 3 performance
      categories: very good (90%-100%), good (80%-89%), and fair (<80%). RESULTS: The
      mean speech perception scores were 88.6% (SD, 14.3%) for postoperative recorded
      speech and 92.3% (SD, 10.7%) for live voice listening, which were significantly
      better than the mean score of 37.2% (SD, 29.1%) listening to recorded voice
      preoperatively. The mean speech perception score was 84.3% (SD, 20.7%) using a
      mobile telephone and 57% (SD, 29.4%) using the standard landline. Further
      analysis showed better performance with mobile phones over standard landlines.
      Seventy-six percent of subjects attained at least good telephone speech
      performance (score >80%). Older patients had poorer telephone speech perception
      than younger patients did. CONCLUSIONS: Many cochlear implant recipients achieve
      good objective telephone speech perception performance, indicating that they
      should be effective telephone users, especially when using mobile telephones and
      among younger implant recipients.

PMID- 21969280
TI  - Spongiotic osteoma of the external auditory canal.

PMID- 21969281
TI  - Influence of birth weight on internalizing traits modulated by serotonergic
      genes.
AB  - OBJECTIVE: Fetal growth predicts childhood behavioral problems associated with
      brain serotonergic systems. We hypothesized that allelic variations in genes
      involved in serotonergic function would moderate associations between birth
      weight (BW) and internalizing traits in childhood. METHODS: The Child Behavior
      Checklist was administered to 545 healthy Singaporean children at 8 to 12 years.
      BW, corrected for gestational age, and candidate single-nucleotide polymorphisms
      (SNPs) in the TPH2, HTR2A, and SCL6A4 genes were investigated. RESULTS: There was
      no significant main effect of BW on internalizing T scores (F = 1.08; P = .36).
      After multiple corrections, significant main effects on internalizing T scores
      were found for HTR2A rs2296972 (adjusted: F = 2.85; P = .019) and HTR2A rs6313
      (adjusted: F = 5.91; P = .0002). Significant interactions were found between BW
      and SNPs for the TPH2 gene (rs2171363: P = .008; rs7305115: P = .007) and the
      HTR2A gene (rs2770304: P = .001; rs6313: P = .026) for internalizing T scores.
      The CC genotype of TPH2 rs2171363, GG genotype of TPH2 rs7305115, CC genotype of
      HTR2A rs2770304, and CC genotype of HTR2A rs6313 were associated with reduced
      internalizing scores for children born in the quartile above the midpoint. No
      significant main effects or interactions were found for SCL6A4 SNPs. CONCLUSIONS:
      These findings suggest that sequence variations in genes involved in serotonergic
      functions modulate relationships between BW and internalizing traits and might be
      candidates for plasticity mechanisms that determine individual differences in
      responses to environmental influences over the course of development.

PMID- 21969282
TI  - Duodenal ulceration in a patient with celiac disease and plasminogen I
      deficiency: coincidence or cofactors?
AB  - Celiac disease (CD) is a gluten-dependent inflammatory disease of the small bowel
      that affects up to 1% of the worldwide population. Despite severe mucosal
      abnormalities including total villous atrophy and autoantibody deposition,
      duodenal ulcer is not a feature of CD. However, a recent study found an elevated
      rate of peptic ulcer disease in patients with CD. Plasminogen deficiency (PLD) is
      an autosomal recessive disease that causes pseudomembranous lesions in different
      organs, but gastrointestinal involvement is rare. Here we report the case of a 6
      year-old girl who had a sudden onset of hematemesis caused by duodenal ulcer. On
      the basis of mucosal atrophy, elevated celiac antibody levels, decreased
      plasminogen serum activity, and homozygous missense mutation R216H in the
      plasminogen gene, CD and PLD were diagnosed. This report is, to our knowledge,
      the first description of the 2 entities, and results of our double
      immunofluorescent studies also suggest that both diseases may have a role in the
      ulceration process. Excessive amounts of fibrin deposition due to PLD caused the
      distortion of the vessels and was responsible for the unusual celiac
      immunoglobulin A and tissue transglutaminase 2 in vivo binding pattern. On the
      basis of this result, patients with CD and unknown cause of gastrointestinal
      ulcer may require investigation for PLD.

PMID- 21969283
TI  - Ovarian teratoma mimicking features of juvenile dermatomyositis in a child.
AB  - An 8-year-old girl complained for 4 months of right arm pain, weakness in both
      legs, difficulty in arising from a seated or squatting position, and 1 month of
      pain in her hips, ankles, and knees. On physical examination, she had weak neck
      flexors, weak proximal and abdominal muscles, and an assisted Gower maneuver;
      both knees and ankles were painful. Erythematous macules on her elbows, knees,
      and medial ankles were present without heliotrope rash or dilated eyelid
      capillaries. She had nail-fold erythema and decreased numbers of nail-fold
      capillary end-row loops (ERLs) (5.42 ERLs per mm [normal: >=6.8 ERLs per mm])
      without digital ulcers or tight skin. Laboratory testing revealed slightly
      elevated creatine phosphokinase (440 IU/L [normal: <=199 IU/L]) and aldolase
      (11.7 U/L [normal: <=8.6 U/L]) levels. Her eosinophilia (7.2%) was not
      characteristic of juvenile dermatomyositis. Rheumatologic evaluation included a
      positive antinuclear antibody test result (1:5120 titer), speckled pattern
      (normal: <80 titer), myositis-associated and -specific antibodies that showed
      indeterminate Mi-2, with the others negative, including p155/140, elevated
      immunoglobulin G (IgG) (1440 mg/dL [normal range: 608-1229]) and IgE (409 kU/L
      [normal: <160 kU/L]) levels, and normal levels of IgM and IgA. She had an
      increased neopterin level (20 nm/L [normal: <10 nm/L]) and decreased absolute
      count of CD3-CD56/16(+) natural killer cells (89 [lower normal limit: 138]). MRI
      of her thigh muscles revealed serpiginous increased T-2 signals consistent with
      inflammation and a complex round mass in the left pelvis. A muscle biopsy did not
      indicate juvenile dermatomyositis. Pelvic ultrasound confirmed a solid mass of
      the left ovary consistent with a mature teratoma. After surgical removal of the
      teratoma, the myositis, synovitis, and cutaneous findings resolved over 4 months
      without further therapy.

PMID- 21969284
TI  - Hyperosmolar dextrose injection for recalcitrant Osgood-Schlatter disease.
AB  - OBJECTIVE: To examine the potential of dextrose injection versus lidocaine
      injection versus supervised usual care to reduce sport alteration and sport
      related symptoms in adolescent athletes with Osgood-Schlatter disease. PATIENTS
      AND METHODS: Girls aged 9 to 15 and boys aged 10 to 17 were randomly assigned to
      either therapist-supervised usual care or double-blind injection of 1% lidocaine
      solution with or without 12.5% dextrose. Injections were administered monthly for
      3 months. All subjects were then offered dextrose injections monthly as needed.
      Unaltered sport (Nirschl Pain Phase Scale < 4) and asymptomatic sport (Nirschl
      Pain Phase Scale = 0) were the threshold goals. RESULTS: Sixty-five knees in 54
      athletes were treated. Compared with usual care at 3 months, unaltered sport was
      more common in both dextrose-treated (21 of 21 vs 13 of 22; P = .001) and
      lidocaine-treated (20 of 22 vs 13 of 22; P = .034) knees, and asymptomatic sport
      was more frequent in dextrose-treated knees than either lidocaine-treated (14 of
      21 vs 5 of 22; P = .006) or usual-care-treated (14 of 21 vs 3 of 22; P < .001)
      knees. At 1 year, asymptomatic sport was more common in dextrose-treated knees
      than knees treated with only lidocaine (32 of 38 vs 6 of 13; P = .024) or only
      usual care (32 of 38 vs 2 of 14; P < .0001). CONCLUSIONS: Our results suggest
      superior symptom-reduction efficacy of injection therapy over usual care in the
      treatment of Osgood-Schlatter disease in adolescents. A significant component of
      the effect seems to be associated with the dextrose component of a
      dextrose/lidocaine solution. Dextrose injection over the apophysis and patellar
      tendon origin was safe and well tolerated and resulted in more rapid and frequent
      achievement of unaltered sport and asymptomatic sport than usual care.

PMID- 21969285
TI  - Ceftriaxone-induced hemolysis in a child with Lyme arthritis: a case for
      antimicrobial stewardship.
AB  - Guidelines for the treatment of Lyme arthritis were published by the Infectious
      Diseases Society of America in 2006 and recommended oral doxycycline for initial
      therapy. We report here the case of a young girl treated with intravenous
      ceftriaxone who subsequently developed drug-induced autoimmune hemolytic anemia
      and renal failure. Her severe sequelae highlight the importance of antimicrobial
      stewardship. We review here the goals of antimicrobial stewardship and several
      strategies for achieving them. In addition, we briefly discuss the rare adverse
      drug event experienced by our patient.

PMID- 21969286
TI  - Incidence and descriptive epidemiologic features of traumatic brain injury in
      King County, Washington.
AB  - OBJECTIVE: Traumatic brain injury (TBI) is a major cause of disability among US
      children. Our goal was to obtain population-based data on TBI incidence rates.
      METHODS: We conducted surveillance through a stratified random sample of hospital
      emergency departments in King County, Washington, to identify children 0 to 17
      years of age with medically treated TBIs during an 18-month study period in 2007
      2008. Additional cases were identified through hospital admission logs and the
      medical examiner's office. For a sample of nonfatal cases, parents were
      interviewed to verify TBIs, and medical record data on severity and mechanisms
      were obtained. RESULTS: The estimated incidence of TBIs in this setting was 304
      cases per 100,000 child-years. The incidence was highest for preschool-aged
      children and lowest for children aged 5 to 9 years. Rates were uniformly higher
      for boys than for girls; there was a larger gender gap at older ages. Falls were
      the main mechanism of injury, especially among preschool-aged children, whereas
      being struck by or against an object and motor vehicle-related trauma were
      important contributors for older children. Approximately 97% of TBI cases were
      mild, although moderate/severe TBI incidence increased with age. CONCLUSIONS:
      TBIs led to many emergency department visits involving children, but a large
      majority of the cases were clinically mild. Incidence rates for King County were
      well below recent national estimates but within the range reported in previous US
      studies. Because mechanisms of injury varied greatly according to age, prevention
      strategies almost certainly must be customized to each age group for greatest
      impact.

PMID- 21969287
TI  - Hyperventilation in pediatric resuscitation: performance in simulated pediatric
      medical emergencies.
AB  - OBJECTIVE: To examine the hypothesis that pediatric resuscitation providers
      hyperventilate patients via bag-valve-mask (BVM) ventilation during performance
      of cardiopulmonary resuscitation (CPR), quantify the degree of excessive
      ventilation provided, and determine if this tendency varies according to provider
      type. METHODS: A retrospective, observational study was conducted of 72
      unannounced, monthly simulated pediatric medical emergencies ("mock codes") in a
      tertiary care, academic pediatric hospital. Responders were code team members,
      including pediatric residents and interns (MDs), respiratory therapists (RTs),
      and nurses (RNs). All sessions were video-recorded and reviewed for the rate of
      BVM ventilation, rate of chest compressions, and the team members performing
      these tasks. The type of emergency, location of the code, and training level of
      the team leader were also recorded. RESULTS: Hyperventilation was present in
      every mock code reviewed. The mean rate of BVM ventilation for all providers in
      all scenarios was 40.6 +/- 11.8 breaths per minute (BPM). The mean ventilation
      rates for RNs, RTs, and MDs were 40.8 +/- 14.7, 39.9 +/- 11.7, and 40.5 +/- 10.3
      BPM, respectively, and did not differ among providers (P = .94). All rates were
      significantly higher than the recommended rate of 8 to 20 BPM (per Pediatric
      Advanced Life Support guidelines, varies with patient age) (P < .001). The mean
      ventilation rate in cases of isolated respiratory arrest was 44.0 +/- 13.9 BPM
      and was not different from the mean BVM ventilation rate in cases of
      cardiopulmonary arrest (38.9 +/- 14.4 BPM; P = .689). CONCLUSIONS:
      Hyperventilation occurred in simulated pediatric resuscitation and did not vary
      according to provider type. Future educational interventions should focus on
      avoidance of excessive ventilation.

PMID- 21969288
TI  - Retinoblastoma in a child after normal autorefraction and traditional vision
      screening.
AB  - Retinoblastoma is an ocular malignancy that can put a patient's sight and, in
      some instances, life at risk. Here we report the case of a 2-year-old child who
      presented to her pediatrician with a 2-week history of left-sided leukocoria
      caused by retinoblastoma. Results of traditional office-based vision screening
      and automated vision screening, which often identify but are not specifically
      designed to detect rare diseases such as retinoblastoma, had been normal in the
      antecedent 7 months. She underwent enucleation of the left eye and has done well
      postoperatively. This case highlights the importance of assessing ocular media
      clarity by using red-reflex testing at multiple intervals during the preschool
      years, particularly in light of the recently published US Preventive Services
      Task Force guidelines for preschool vision screening, which gave an "insufficient
      evidence" level for vision screening in children younger than 3 years and failed
      to address red-reflex examination.

PMID- 21969289
TI  - Cognitive and behavioral outcomes after early exposure to anesthesia and surgery.
AB  - BACKGROUND: Annually, millions of children are exposed to anesthetic agents that
      cause apoptotic neurodegeneration in immature animals. To explore the possible
      significance of these findings in children, we investigated the association
      between exposure to anesthesia and subsequent (1) learning disabilities (LDs),
      (2) receipt of an individualized education program for an emotional/behavior
      disorder (IEP-EBD), and (3) scores of group-administered achievement tests.
      METHODS: This was a matched cohort study in which children (N = 8548) born
      between January 1, 1976, and December 31, 1982, in Rochester, Minnesota, were the
      source of cases and controls. Those exposed to anesthesia (n = 350) before the
      age of 2 were matched to unexposed controls (n = 700) on the basis of known risk
      factors for LDs. Multivariable analysis adjusted for the burden of illness, and
      outcomes including LDs, receipt of an IEP-EBD, and the results of group
      administered tests of cognition and achievement were outcomes. RESULTS: Exposure
      to multiple, but not single, anesthetic/surgery significantly increased the risk
      of developing LDs (hazard ratio: 2.12 [95% confidence interval: 1.26-3.54]), even
      when accounting for health status. A similar pattern was observed for decrements
      in group-administered tests of achievement and cognition. However, exposure did
      not affect the rate of children receiving an individualized education program.
      CONCLUSIONS: Repeated exposure to anesthesia and surgery before the age of 2 was
      a significant independent risk factor for the later development of LDs but not
      the need for educational interventions related to emotion/behavior. We cannot
      exclude the possibility that multiple exposures to anesthesia/surgery at an early
      age may adversely affect human neurodevelopment with lasting consequence.

PMID- 21969290
TI  - Alternative vaccination schedule preferences among parents of young children.
AB  - OBJECTIVE: Increasing numbers of parents use alternative vaccination schedules
      that differ from the recommended childhood vaccination schedule for their
      children. We sought to describe national patterns of alternative vaccination
      schedule use and the potential "malleability" of parents' current vaccination
      schedule choices. METHODS: We performed a cross-sectional, Internet-based survey
      of a nationally representative sample of parents of children 6 months to 6 years
      of age. Bivariate and multivariate analyses determined associations between
      demographic and attitudinal factors and alternative vaccination schedule use.
      RESULTS: The response rate was 61% (N = 748). Of the 13% of parents who reported
      following an alternative vaccination schedule, most refused only certain vaccines
      (53%) and/or delayed some vaccines until the child was older (55%). Only 17%
      reported refusing all vaccines. In multivariate models, nonblack race and not
      having a regular health care provider for the child were the only factors
      significantly associated with higher odds of using an alternative schedule. A
      large proportion of alternative vaccinators (30%) reported having initially
      followed the recommended vaccination schedule. Among parents following the
      recommended vaccination schedule, 28% thought that delaying vaccine doses was
      safer than the schedule they used, and 22% disagreed that the best vaccination
      schedule to follow was the one recommended by vaccination experts. CONCLUSIONS:
      More than 1 of 10 parents of young children currently use an alternative
      vaccination schedule. In addition, a large proportion of parents currently
      following the recommended schedule seem to be "at risk" for switching to an
      alternative schedule.

PMID- 21969291
TI  - The pediatrician and anesthesia neurotoxicity.

PMID- 21969292
TI  - Influenza A/H1N1/09-10 infections in a NICU during the 2009-2010 H1N1 pandemic.
AB  - Few cases of the pandemic influenza A H1N1 have been reported in very low birth
      weight infants. We report here a small outbreak in our NICU of 3 cases of
      influenza A/H1N1/09-10 in very low birth weight infants during the 2009-2010 H1N1
      pandemic and describe their clinical presentations and favorable outcomes despite
      the lack of treatment.

PMID- 21969294
TI  - Effect of glaucoma on the quality of life of young patients.
AB  - PURPOSE: To evaluate the quality of life (QOL) of juvenile-onset primary open
      angle glaucoma (JOAG) patients by using a utility-based assessment. METHODS: QOL
      using time-tradeoff utility values was analyzed in 70 JOAG patients and compared
      with 108 adult-onset POAG patients. The relationships of utility values to
      parameters like age at diagnosis, visual acuity, mean deviation, number of
      medications and surgery, duration of the disease, level of education, and
      socioeconomic status were assessed. RESULTS: The mean age at diagnosis of JOAG
      patients was 26 +/- 9.8 years, whereas that of the adult onset POAG patients was
      62 +/- 11.2 years. Overall, there was a decrease in utility values with
      increasing age (r = -0.3; P < 0.001). The mean utility score among JOAG patients
      was (0.80 +/- 0.18) significantly greater than among adult POAG patients (0.64 +/
      0.28; P < 0.001). The differences in utility scores between JOAG and adult POAG
      patients were significant when adjusted for differences in better eye visual
      acuity, mean deviation, and the presence of systemic comorbidity among adults (P
      = 0.02). Among JOAG patients, those needing topical antiglaucoma medications and
      those with visual acuity worse than 6/12 in the better eye had lower utility
      values (P = 0.008 and P = 0.002, respectively). CONCLUSIONS: Utility values among
      glaucoma patients in the juvenile age group are better than those of adult POAG
      patients. Decreasing vision in the better eye and having to use medication
      decrease the utility scores among young patients with glaucoma.

PMID- 21969293
TI  - Expression and functional roles of caspase-5 in inflammatory responses of human
      retinal pigment epithelial cells.
AB  - PURPOSE: To investigate the expression, activation, and functional involvement of
      caspase-5 in human retinal pigment epithelial (hRPE) cells. METHODS: Expression
      and activation of caspase-5 in primary cultured hRPE cells, telomerase
      immortalized hTERT-RPE1 cells (hTERT-RPE1), or both, were measured after
      stimulation with proinflammatory agents IL-1beta, TNF-alpha, lipopolysaccharide
      (LPS), interferon-gamma, monocyte coculture, adenosine triphosphate (ATP), or
      endoplasmic reticulum (ER) stress inducers. Immunomodulating agents dexamethasone
      (Dex), IL-10, and triamcinolone acetonide (TA) were used to antagonize
      proinflammatory stimulation. Cell death ELISA and TUNEL staining assays were used
      to assess apoptosis. RESULTS: Caspase-5 mRNA expression and protein activation
      were induced by LPS and monocyte-hRPE coculture. Caspase-5 activation appeared as
      early as 2 hours after challenge by LPS and consistently increased to 24 hours.
      Meanwhile, caspase-1 expression and protein activation were induced by LPS.
      Activation of caspase-5 was blocked or reduced by Dex, IL-10, and TA. Activation
      of caspase-5 and -1 was also enhanced by ATP and ER stress inducers. Expression
      and activation of caspase-5 were inhibited by a caspase-1-specific inhibitor.
      Caspase-5 knockdown reduced caspase-1 protein expression and activation and
      inhibited TNF-alpha-induced IL-8 and MCP-1. In contrast to caspase-4, the
      contribution of caspase-5 to stress-induced apoptosis was moderate. CONCLUSIONS:
      Caspase-5 mRNA synthesis, protein expression, and catalytic activation were
      highly regulated in response to various proinflammatory stimuli, ATP, and ER
      stress inducers. Mutual activation between caspase-5 and -1 suggests caspase-5
      may work predominantly in concert with caspase-1 in modulating hRPE inflammatory
      responses.

PMID- 21969295
TI  - Substance P in the corneal stroma regulates the severity of herpetic stromal
      keratitis lesions.
AB  - PURPOSE: To determine whether substance P (SP) in herpes simplex virus-1 (HSV-1)
      infected cornea regulates the severity of herpetic stromal keratitis (HSK)
      lesions in a mouse model. METHODS: C57BL/6 mice were infected ocularly with HSV-1
      (RE). The corneas with HSK lesions, on Day 15 postinfection, were grouped on the
      basis of the corneal opacity as mild (<=2) or severe (>2). The amount of SP was
      determined in the corneas with mild or severe HSK lesions by enzyme immunosorbent
      assay (EIA) and confocal microscopy. Subconjunctival inoculation of spantide I,
      SP receptor antagonist, was carried out during the clinical phase of HSK. ELISA
      and flow cytometry were used to determine the level of cytokines, chemokines, and
      influx of immune cell types in the corneal lesions. RESULTS: The authors
      determined a significantly higher level of SP in the corneas with severe HSK
      lesions in comparison with mild lesions. The corneas with a higher level of SP
      also exhibited higher amounts of proinflammatory cytokines (IL-6, IFN-gamma) and
      chemokines (CCL3, CXCL2) when compared with the corneas with a lower level of SP.
      SP receptor NK1R expression was determined in CD45- and CD45+ cells in infected
      cornea. SP present in the corneal stroma of the eyes with severe HSK lesions
      colocalized with beta-III tubulin(+) and IA(b+) cell types. Subconjunctival
      inoculation of spantide I during the clinical phase of HSK resulted in
      significant reduction in the corneal opacity and angiogenesis. CONCLUSIONS:
      Collectively, these results demonstrate the relative contribution of substance P
      in regulating the clinical severity of HSK lesions in a mouse model.

PMID- 21969296
TI  - Independent impact of area-level socioeconomic measures on visual impairment.
AB  - PURPOSE: It is known that a person's socioeconomic status (SES; individual-level
      SES) is closely correlated with his or her degree of visual impairment. Whether
      there is an independent relationship between area-level measures of SES (e.g.,
      living in a lower SES environment) and visual impairment is unclear. This study
      describes the associations of area-level SES with visual impairment. METHODS: The
      authors conducted two population-based cross-sectional studies of 3280 adult
      Malays and 3400 adult Indians living in Singapore. Visual impairment was defined
      as LogMAR visual acuity >0.30 in the better-seeing eye. Area-level SES measures
      (e.g., proportion of people not speaking English, proportion of people with low
      income) were derived from the Singapore's 2000 population census. RESULTS:
      Increasing age and individual-level SES measures (including lower education
      level, lower income level, and lower occupational status) were significantly
      associated with increased odds of visual impairment. In analyses adjusting for
      age and individual-level SES measures, many area-level SES measures (e.g., higher
      proportion of people not using English, higher proportion of people with low
      income) were also significantly associated with increased odds of visual
      impairment. These associations were consistently observed in both Malays and
      Indians. CONCLUSIONS: These data suggest that not only is a person's SES, but the
      SES of his or her immediate community, is associated with visual impairment.
      Further research is needed to investigate the underlying causes of visual health
      disparities and to improve the eye health of communities with lower SES.

PMID- 21969297
TI  - An enzymatic technique to facilitate air separation of the stroma-Descemet's
      membrane junction.
AB  - PURPOSE: To describe an enzymatic technique that facilitates air separation of
      Descemet's membrane from the corneal stroma. METHODS: Fresh human corneoscleral
      tissue was mounted on an artificial anterior chamber. In a control group, air was
      injected into the stroma. A second group received a stromal injection of 2.5
      mg/mL collagenase type 2 in balanced salt solution that was left in the stroma
      for 1 hour and 15 minutes. A third group received an injection of 2.5 mg/mL
      collagenase type 2 in balanced salt solution followed 1 hour and 15 minutes later
      by an injection of air into the stroma. All injections were performed with a 27
      gauge needle into the deep stroma without penetrating Descemet's membrane.
      Anterior segment optical coherence tomography (AS-OCT), histologic examination,
      and electron microscopy of the junction between the stroma and Descemet's
      membrane were performed. The trypan blue exclusion and TUNEL assays were used to
      study endothelial cell viability after collagenase incubation. RESULTS: Injection
      of air or collagenase into the deep corneal stroma did not result in a
      reproducible separation of the stroma-Descemet's junction. In contrast, the
      stroma was easily and reproducibly separated from Descemet's membrane with a
      combination of intrastromal collagenase and air injection. The separation was
      confirmed by using light and electron microscopy. The cleavage plane seemed to be
      located between the junction of the posterior stroma and the anterior banded
      layer of Descemet's membrane. Trypan blue staining demonstrated the viability of
      endothelial cells after collagenase incubation. TUNEL assay confirmed excellent
      viability after collagenase+air separation. CONCLUSIONS: This technique
      facilitates the separation of Descemet's membrane from the stroma without
      affecting endothelial cell viability.

PMID- 21969298
TI  - Oxidative stress in keratoconus?
AB  - PURPOSE: The purpose of this study was to establish the alterations of oxidative
      stress-related markers in keratoconus (KC) corneas. METHODS: A total of 6 healthy
      and 11 ectatic corneas (7 KC and 4 post-LASIK) were studied. Different oxidative
      stress-related markers were determined to assess their implication in the KC
      pathophysiology. Total antioxidant capacity and total nitrites present in the
      samples were assayed. Furthermore, lipid peroxidation products and the
      glutathione contents were determined, together with 4-hydroxynonenal (4-HNE)
      immunohistochemistry, to establish the relationship between KC and oxidative
      stress. RESULTS: The antioxidant capacity and glutathione content in KC corneas
      were decreased significantly when compared with healthy corneas. Moreover, the
      total nitrites and lipid peroxidation were significantly elevated in the corneas
      with KC when compared with the controls. There was a statistically significant
      difference in the amount of HNE-positive cells in KC corneas when compared with
      healthy corneas by immunohistochemistry. Post-LASIK ectatic corneas and KC
      corneas showed similar results. CONCLUSIONS: The increased levels of oxidative
      stress markers and the decreased antioxidant capacity and antioxidant defenses in
      KC corneas, as well as in the post-LASIK ectatic corneas, indicate that oxidative
      stress might be involved in the development of this disease and may provide new
      insights for its prevention and treatment in the future.

PMID- 21969299
TI  - Mechanical interferometry imaging for creep modeling of the cornea.
AB  - PURPOSE: A novel nanoindentation technique was used to biomechanically
      characterize each of three main layers of the cornea by using Hertzian
      viscoelastic formulation of creep, the deformation resulting from sustained-force
      application. METHODS: The nanoindentation method known as mechanical
      interferometry imaging (MII) with <1-nm displacement precision was used to
      observe indentation of bovine corneal epithelium, endothelium, and stroma by a
      spherical ferrous probe in a calibrated magnetic field. For each specimen, creep
      testing was performed using two different forces for 200 seconds. Measurements
      for single force were used to build a quantitative Hertzian model that was then
      used to predict creep behavior for another imposed force. RESULTS: For all three
      layers, displacement measurements were highly repeatable and were well predicted
      by Hertzian models. Although short- and long-term stiffnesses of the endothelium
      were highest of the three layers at 339.2 and 20.2 kPa, respectively, both
      stromal stiffnesses were lowest at 100.4 and 3.6 kPa, respectively. Stiffnesses
      for the epithelium were intermediate at 264.6 and 12.2 kPa, respectively.
      CONCLUSIONS: Precise, repeatable measurements of corneal creep behavior can be
      conveniently obtained using MII at mechanical scale as small as one cell
      thickness. When interpreted in analytical context of Hertzian viscoelasticity,
      MII technique proved to be a powerful tool for biomechanical characterization of
      time-dependent biomechanics of corneal regions.

PMID- 21969300
TI  - Role of connective tissue growth factor in the retinal vasculature during
      development and ischemia.
AB  - PURPOSE: To investigate the function of connective tissue growth factor (CTGF), a
      matricellular protein of the CCN (Cyr61/CTGF/Nov) family, in retinal vasculature
      during development and ischemia. METHODS: CTGF expression was determined using RT
      PCR, immunohistochemistry, and transgenic mice carrying CTGF promoter-driven-GFP.
      CTGF antibody was intraocularly injected into neonates at postnatal day (P)2, and
      its effect on retinal angiogenesis was analyzed at P4. Transgenic animals
      expressing GFP regulated by the glial fibrillary acidic protein promoter were
      used for astrocyte visualization. Retinal vascular occlusion was introduced by
      rose Bengal and laser photocoagulation on chimeric mice that were reconstituted
      with GFP+ bone marrow cells. Vascular repair in response to VEGF-A and CTGF was
      analyzed. RESULTS: A temporal increase in CTGF at both mRNA and protein levels
      was observed in the ganglion cell layer and inner nuclear layer during
      development. Endothelial cells and pericytes were identified as the main cellular
      sources of CTGF during retinal angiogenesis. CTGF stimulated the migration of
      astrocytes, retinal endothelial cells, and pericytes in vitro. Inhibition of CTGF
      by specific antibody affected vascular filopodial extension, growth of the
      superficial vascular plexus, and astrocyte remodeling. In adult mice, CTGF was
      prominently expressed in the perivascular cells of arteries. CTGF activated bone
      marrow-derived perivascular cells and promoted fibrovascular membrane formation
      in the laser-induced adult retinopathy model. CONCLUSIONS: CTGF is expressed in
      vascular beds and acts on multiple cell types. It is important for vessel growth
      during early retinal development and promotes the fibrovascular reaction in
      murine retinal ischemia after laser injury.

PMID- 21969301
TI  - Egr1 expression is induced following glatiramer acetate immunotherapy in rodent
      models of glaucoma and Alzheimer's disease.
AB  - PURPOSE: Immunization with glatiramer acetate (GA) alleviates the neuropathology
      associated with glaucoma and Alzheimer's disease (AD) in rodent models. This
      research was undertaken to screen for molecular factors underlying GA-induced
      neuroprotective mechanisms in these models of chronic neurodegeneration. METHODS:
      Gene expression profiles were analyzed in GA-immunized versus nonimmunized
      elevated-intraocular pressure (IOP) rat models of glaucoma by using whole genome
      cDNA microarrays and were further validated by quantitative real-time PCR
      analysis. A gene, prominently upregulated by GA in elevated IOP retina, was
      further studied in APP(SWE)/PS1(DeltaE9)-transgenic (AD-Tg) mice after GA
      immunization. RESULTS: Seven days after treatment with GA, numerous genes were
      regulated in the retinas of rats with elevated IOP. Comprehensive functional
      classification and DAVID/KEGG enrichment analysis of GA-induced differentially
      expressed genes revealed annotation terms and pathways involved in
      neuroprotection, immune responses, cell communication, and regeneration.
      Specifically, increased mRNA levels of an early growth response (Egr) 1 gene were
      evident in GA-immunized retinas with elevated IOP. In AD-Tg mice, a significant
      increase in hippocampal EGR1 protein levels was also found in response to GA
      immunization. Nuclear EGR1 in the dentate gyrus colocalized more frequently with
      doublecortin-positive and Ki67 proliferating neural progenitors in GA-immunized
      as compared to nonimmunized AD-Tg mice. Further, EGR1 levels were negatively
      correlated with hippocampal amyloid-beta plaque burden. CONCLUSIONS: This study
      presents global gene expression profiles associated with GA immunization in a
      glaucoma rat model. Moreover, it identifies EGR1 transcription factor as a
      potential mediator for GA-induced neuroprotection in both glaucoma and AD.

PMID- 21969302
TI  - Neurotransmitter influence on human meibomian gland epithelial cells.
AB  - PURPOSE: A striking characteristic of the human meibomian gland is its rich
      sensory, sympathetic, and parasympathetic innervation, yet the functional
      relevance of these nerve fibers remains unknown. Acting on the hypothesis that
      neurotransmitters are released in the vicinity of the gland, act on glandular
      receptors, and influence the production, secretion, and/or delivery of meibomian
      gland secretions to the ocular surface, the goal in this study was to begin to
      determine whether neurotransmitters influence the meibomian gland. METHODS:
      Immortalized human meibomian gland epithelial (SLHMG) cells were examined for the
      presence of vasoactive intestinal peptide (VIP) and muscarinic acetylcholine
      (mACh) receptor transcripts and proteins. Cells were also exposed to VIP,
      carbachol, forskolin, and/or 3-isobutyl-1-methylxanthine (IBMX) to determine
      whether these agents, alone or in combination, modulate the adenylyl cyclase
      pathway, the accumulation of intracellular free calcium ([Ca2+]i), or cell
      proliferation. RESULTS: Results demonstrate that SLHMG cells transcribe and
      translate VIP and mACh receptors; VIP, with either IBMX or forskolin, activates
      the adenylyl cyclase pathway, and the effect of VIP and forskolin together is
      synergistic; both VIP and carbachol increase intracellular [Ca2+] in SLHMG cells;
      and VIP with forskolin stimulates SLHMG cell proliferation. CONCLUSIONS: This
      study shows that parasympathetic neurotransmitters and their agonists influence
      the function of human meibomian gland epithelial cells. It remains to be
      determined whether this action alters the production, secretion, and/or delivery
      of meibum to the ocular surface.

PMID- 21969303
TI  - Measurement of ocular fundus pulsation in healthy subjects using a novel Fourier
      domain optical coherence tomography.
AB  - PURPOSE: Anomalies in the pulsatility of the eye have been associated with many
      types of ocular pathology. Estimation of ocular pulsatility is usually obtained
      by measuring the variation in the intraocular pressure using tonometry-based
      instruments. In this work, the authors present and demonstrate the applicability
      of a novel and noninvasive Fourier-domain optical coherence tomography (FD-OCT)
      system to measure pulsatile ocular tissue movements. METHODS: The authors
      simultaneously measured the longitudinal movement of the cornea and the retina
      driven by the cardiac cycle in 21 healthy volunteers using their custom-made FD
      OCT. They calculated the corresponding fundus pulse amplitude (FPA), which is the
      variation in the distance between the cornea and the retina. RESULTS: It was
      found that in young, healthy subjects, the cornea and the retina move axially
      during the cardiac cycle, with almost equal amplitude but with a phase difference
      ranging between 1 degrees  and 20 degrees . The measured FPA was found to be
      mostly due to the relative phase difference between corneal and retinal
      movements, and frequency analysis revealed the presence of the harmonics of
      heartbeat. The root-mean-square values for cornea, retina, and FPA movements were
      found to be 28 +/- 9 MUm, 29 +/- 9 MUm, and 4 +/- 2 MUm, respectively. The
      dominant frequency component in corneal and retinal movement was found to be the
      second harmonic of the heartbeat. CONCLUSIONS: The technique described here is
      useful for a precise description of FPA and the movement of ocular tissues.
      Further investigations and technical improvements will be beneficial for
      understanding the role of choroidal pulsation in the pathophysiology of ocular
      diseases.

PMID- 21969304
TI  - Storage effects on anthocyanins, phenolics and antioxidant activity of thermally
      processed conventional and organic blueberries.
AB  - BACKGROUND: Consumer demand for products rich in phytochemicals is increasing as
      a result of greater awareness of their potential health benefits. However,
      processed products are stored for long-term and the phytochemicals are
      susceptible to degradation during storage. The objective of this study was to
      assess the storage effects on phytochemicals in thermally processed blueberries.
      Thermally processed canned berries and juice/puree were analysed for
      phytochemicals during their long-term storage. RESULTS: The phytochemical
      retention of thermally processed blueberries during storage was not influenced by
      production system (conventional versus organic). During 13 months of storage,
      total anthocyanins, total phenolics and total antioxidant activity in canned
      blueberry solids decreased by up to 86, 69 and 52% respectively. In canned
      blueberry syrup, total anthocyanins and total antioxidant activity decreased by
      up to 68 and 15% respectively, while total phenolic content increased by up to
      117%. Similar trends in phytochemical content were observed in juice/puree stored
      for 4 months. The extent of changes in phytochemicals of thermally processed
      blueberries during storage was significantly influenced by blanching. CONCLUSION:
      Long-term storage of thermally processed blueberries had varying degrees of
      influence on degradation of total anthocyanins, total phenolics and total
      antioxidant activity. Blanching before thermal processing helped to preserve the
      phytochemicals during storage of blueberries.

PMID- 21969305
TI  - Auger-decay dynamics of germanium nano-islands in silicon.
AB  - The decay dynamics of self-assembled germanium islands is studied by time
      resolved fluorescence spectroscopy. The scaling behavior of the decay rate with
      the number of excitons in the islands is shown to agree with expectations for an
      Auger-recombination-dominated process in the asymptotic limit of high exciton
      numbers. The multi-excitonic decay time and spectral behavior are compared to
      theoretical estimates.

PMID- 21969306
TI  - Non-compartmental estimation of pharmacokinetic parameters for flexible sampling
      designs.
AB  - Pharmacokinetic (PK) studies aim to understand the kinetics of absorption,
      distribution, metabolism and elimination of a drug. Typically, such studies
      involve measuring the concentration of the drug in the plasma or blood at several
      time points after drug administration. In studying the PK behaviour, either the
      non-compartmental approach or alternatively a modelling approach can be utilized.
      Traditionally, the non-compartmental approach makes minimal assumptions about the
      data-generating process but requires the data to be collected in a very
      structured way. Conversely, the modelling approach depends heavily on assumptions
      about the data-generating process but does not impose a specific data structure.
      In this paper, we will discuss non-compartmental methods for estimating the area
      under the concentration versus time curve and other common PK parameters that use
      minimal assumptions about the data structure making it applicable to a wide range
      of PK studies. We will evaluate the methods using simulation and give an
      illustrative example.

PMID- 21969308
TI  - Nanoscale, catalytically enhanced local oxidation of silicon-containing layers by
      'burrowing' Ge quantum dots.
AB  - A new phenomenon of highly localized, nanoscale oxidation of silicon-containing
      layers has been observed. The localized oxidation enhancement observed in both Si
      and Si(3)N(4)  layers appears to be catalyzed by the migration of Ge quantum dots
      (QDs). The sizes, morphology, and distribution of the Ge QDs are influenced by
      the oxidation of the Si-bearing layers. A two-step mechanism of dissolution of Si
      within the Ge QDs prior to oxidation is proposed.

PMID- 21969307
TI  - Variations in glutathione-S-transferase genes influence risk of chronic myeloid
      leukemia.
AB  - Glutathione S-transferases (GSTs) are phase II enzymes that detoxify hazardous
      xenobiotics including carcinogens. Inter-individual variations in GSTM1 and GSTT1
      loci have been associated with several types of cancer, including leukemias. In
      this study, we investigated the possible association between GSTM1 and GSTT1
      polymorphisms and susceptibility to chronic myeloid leukemia (CML) in a Turkish
      population. In a case-control study, 106 CML patients and 190 healthy controls
      were evaluated for GSTM1 and GSTT1 polymorphisms. GSTM1 null (GSTM1(-)) genotype
      frequencies in CML cases and controls were 45.3% and 42.6%, respectively. GSTT1
      null (GSTT1(-)) genotype frequencies were 44.3% and 18.4%, respectively. The
      frequency of the GSTT1(-) genotype among CML patients was significantly higher
      than in controls [odds ratio (OR) 3.53, 95% confidence interval (CI) 2.08-6.00; P
      < 0.0001]. Individuals with the GSTM1(-) genotype did not have increased risk of
      CML [OR: 1.11; 95% CI: 0.69-1.80; P = 0.714]. The combined GSTM1(-)/GSTT1(-)
      genotype was significantly associated with risk of CML compared to the GSTM1(+)
      /GSTT1(+) genotype which was most frequent in both cases and controls [OR: 9.47;
      95% CI: 3.61-24.87]. Similar findings have only been obtained in Turkish and
      Indian populations but not elsewhere. The GSTM1(+) /GSTT1(-) genotype was
      associated with a 2.5-fold increased risk compared with the GSTM1(-)/GSTT1(+)
      genotype, the second most frequent genotype (OR; 2.46; 95% CI: 1.17, 5.20),
      suggesting a complex interaction between GSTM1 and GSTT1. Our results indicate an
      association between the GSTT1(-) genotype, either alone or in combination with
      GSTM1(-) genotype, and risk of CML, suggesting a possible interaction between
      GSTM1 and GSTT1. These findings, which are possibly restricted to Turkey and
      India, warrant further research.

PMID- 21969309
TI  - Issues and needs in end-of-life decision making: an international modified Delphi
      study.
AB  - BACKGROUND: end-of-life decision making is an important aspect of end-of-life
      care that can have a significant impact on the process of dying and patients'
      comfort in the last days of life. AIM: the aim of our study was to identify
      issues and considerations in end-of-life decision making, and needs for more
      evidence among palliative care experts, across countries and professions.
      PARTICIPANTS: 90 palliative care experts from nine countries participated in a
      modified Delphi study. Participants were asked to identify important issues and
      considerations in end-of-life decision making and to rate the need for more
      evidence. RESULTS: experts mentioned 219 issues in end-of-life decision making
      related to the medical domain, 122 issues related to the patient wishes and 92
      related to relatives' wishes, regardless of profession or country (p > 0.05). In
      accordance, more than 90% of the experts rated the comfort and wishes of the
      patient and the potential futility of treatment as important considerations in
      end-of-life decision making, although some variation was present. When asked
      about issues that are in need of more evidence, 87% mentioned appropriate
      indications for using sedatives and effects of artificial hydration at the end of
      life. A total of 83% mentioned adequate communication approaches. CONCLUSIONS:
      palliative care experts from different professions in different countries
      encounter similar issues in end-of-life decision making. Adequate communication
      about these issues is universally experienced as a challenge, which might benefit
      from increased knowledge. This shared experience enables and emphasizes the need
      for more international research.

PMID- 21969310
TI  - Barriers and facilitators to the receipt of palliative care for people with
      dementia: the views of medical and nursing staff.
AB  - BACKGROUND: The global prevalence of dementia is set to rise to almost 65 million
      people by 2030, providing policy makers and practitioners with significant
      challenges, not least within the realms of end-of-life care. The international
      literature would suggest that people with dementia may benefit from palliative
      forms of care, but evidence indicates that many fail to access such provision at
      the end of life. The role of the health care team is pivotal if people with
      dementia are to benefit from the transition to palliative care. AIM: This paper
      reports on qualitative research conducted in the UK that sought to explore the
      experiences of health care practitioners working in palliative care and sought to
      establish the issues relating to end-of-life care for people with dementia.
      DESIGN: Eight focus groups and four individual interviews were held. Data were
      analysed using a thematic approach. SETTING/PARTICIPANTS: The study included
      palliative care practitioners (n = 58) including medical, nursing and allied
      health professionals. Participants were recruited from acute hospitals, general
      practice, hospices and specialist palliative care units in the UK. RESULTS: Four
      themes were identified: Making the transition; Competence challenged; 'The long
      view' and Working together. Whilst there exists good practice in this area, the
      barriers to timely and appropriate transitions to palliative care for people with
      dementia and their families continue to exist. The paper concludes with
      recommendations for policy and practice development.

PMID- 21969311
TI  - High doses of salicylate and aspirin are inhibitory on acid-sensing ion channels
      and protective against acidosis-induced neuronal injury in the rat cortical
      neuron.
AB  - Aspirin and its main metabolite salicylate are widely used to relieve pain, treat
      inflammatory diseases, and prevent ischemic stroke. Multiple pathways are
      responsible for the therapeutic actions exerted by these drugs. One of the
      pathways is targeting neuronal receptors/ion channels in the central nervous
      system. Correspondingly, increasing evidence has implicated acid-sensing ion
      channels (ASICs) in the processes of the diseases that are medicated by aspirin
      and salicylate. We therefore employed whole-cell patch-clamp recordings to
      examine the effects of salicylate as well as aspirin on ASICs in cultured
      cortical neurons of the rat. We recorded rapid and reversible inhibition of ASIC
      current by millimolar concentrations of aspirin and salicylate and found that
      salicylate reduced acidosis-induced membrane depolarization. These data suggest
      that ASICs in the cortex are molecular targets of high doses of aspirin and
      salicylate. In addition, the results from lactate dehydrogenase release
      measurement showed that high doses of aspirin and salicylate protected the
      cortical neuron from acidosis-induced neuronal injury. These findings may
      contribute to a better understanding of the therapeutic mechanisms of aspirin and
      salicylate actions in the brain and provide new evidence on aspirin and
      salicylate used as neuroprotective agents in the treatment of ischemic stroke.

PMID- 21969313
TI  - Prospective validity of the Estimate of Risk of Adolescent Sexual Offense
      Recidivism (ERASOR).
AB  - Data from the Estimate of Risk of Adolescent Sexual Offense Recidivism (ERASOR;
      Worling & Curwen) were collected for a sample of 191 adolescent males who had
      offended sexually. Adolescents were aged 12 to 19 years (M = 15.34; SD = 1.53) at
      the time of their participation in a comprehensive assessment. The ERASOR was
      completed by 1 of 22 clinicians immediately following each assessment. Forty-five
      adolescents were independently rated by pairs of clinicians, and significant
      interrater agreement was found for the ERASOR risk factors, the clinical judgment
      ratings (low, moderate, or high), and a total score. Recidivism data (criminal
      charges) were subsequently collected from three sources that spanned a follow-up
      period between 0.1 and 7.9 years (M = 3.66; SD = 2.08). Overall, 9.4% (18 of 191)
      of the adolescents were charged with a subsequent sexual offense over this time
      period. A shorter follow-up interval of up to 2.5 years (M = 1.4; SD = 0.71) was
      also examined. Recidivism data for the shorter follow-up interval were available
      for a subgroup of 70 adolescents, with a comparable recidivism rate of 8.6% (6 of
      70). Clinical judgment ratings, the total score, and the sum of risk factors
      rated as present were significantly predictive of sexual reoffending for the
      short follow-up period. The total score and the sum of risk factors were
      predictive of sexual reoffending over the entire follow-up interval. These
      results add to the emerging research supporting the reliability and validity of
      structured risk assessment tools for adolescent sexual recidivism.

PMID- 21969312
TI  - Short-term music training enhances verbal intelligence and executive function.
AB  - Researchers have designed training methods that can be used to improve mental
      health and to test the efficacy of education programs. However, few studies have
      demonstrated broad transfer from such training to performance on untrained
      cognitive activities. Here we report the effects of two interactive computerized
      training programs developed for preschool children: one for music and one for
      visual art. After only 20 days of training, only children in the music group
      exhibited enhanced performance on a measure of verbal intelligence, with 90% of
      the sample showing this improvement. These improvements in verbal intelligence
      were positively correlated with changes in functional brain plasticity during an
      executive-function task. Our findings demonstrate that transfer of a high-level
      cognitive skill is possible in early childhood.

PMID- 21969314
TI  - Comment on "The inhibiting Fc receptor for IgG, FcgammaRIIB, is a modifier of
      autoimmune susceptibility".

PMID- 21969315
TI  - MicroRNAs regulate dendritic cell differentiation and function.
AB  - MicroRNAs (miRNAs) are an important class of cellular regulators that modulate
      gene expression and thereby influence cell fate and function. In the immune
      system, miRNAs act at checkpoints during hematopoietic development and cell
      subset differentiation, they modulate effector cell function, and they are
      implicated in the maintenance of homeostasis. Dendritic cells (DCs), the
      professional APCs involved in the coordination of adaptive immune responses, are
      also regulated by miRNAs. Some DC-relevant miRNAs, including miR-155 and miR
      146a, are shared with other immune cells, whereas others have been newly
      identified. In this review, we summarize the current understanding of where
      miRNAs are active during DC development from myeloid precursors and
      differentiation into specialized subsets, and which miRNAs play roles in DC
      function.

PMID- 21969316
TI  - Changing reflections of the coronary microcirculation after percutaneous aortic
      valve replacement: novel observations with arterial pulsed wave dynamics.

PMID- 21969317
TI  - Reversal of new oral anticoagulants.

PMID- 21969319
TI  - Thrombus formation on a left atrial appendage closure device.

PMID- 21969318
TI  - Hyperpolarized magnetic resonance: a novel technique for the in vivo assessment
      of cardiovascular disease.

PMID- 21969320
TI  - Deficiencies of natural anticoagulants, protein C, protein S, and antithrombin.

PMID- 21969321
TI  - Idiopathic pulmonary artery aneurysm.

PMID- 21969323
TI  - Letter by Angelini regarding article, "long-term outcome and impact of surgery on
      adults with coronary arteries originating from the opposite coronary cusp".

PMID- 21969324
TI  - Letter by Taegtmeyer and Khalaf regarding article, "Glucose-insulin-potassium
      reduces the incidence of low cardiac output episodes after aortic valve
      replacement for aortic stenosis in patients with left ventricular hypertrophy:
      results from the hypertrophy, insulin, glucose, and electrolytes (HINGE) trial".

PMID- 21969325
TI  - Modulation of peripheral sensory neurons by the immune system: implications for
      pain therapy.
AB  - The concept that the immune system can communicate with peripheral sensory
      neurons to modulate pain is based mostly on documented interactions between
      opioid ligands and receptors. Such findings may have broad implications for the
      development of safer pain medication. Innovative strategies take into account
      that analgesics should be particularly active in pathological states rather than
      producing a general suppression of the central nervous system, as with
      conventional morphine- or cannabinoid-like drugs. Inflammation of peripheral
      tissue leads to increased functionality of opioid receptors on peripheral sensory
      neurons and to local production of endogenous opioid peptides. In addition,
      endocannabinoids were detected in leukocytes, but their role in pain modulation
      has yet to be addressed. Future aims include the development of peripherally
      restricted opioid agonists, selective targeting of opioid-containing immune cells
      to sites of painful injury, and the augmentation of peripheral ligand and
      receptor synthesis (e.g., by gene therapy). Similar approaches may be pursued for
      cannabinoids. The ultimate goal is to avoid detrimental side effects of currently
      available analgesics such as respiratory depression, cognitive impairment,
      addiction, gastrointestinal bleeding, and thromboembolic complications.

PMID- 21969328
TI  - The prescription of oral contraceptives and its relation to the incidence of
      chlamydia and abortion in Sweden 1997-2005.
AB  - AIMS: The aim of this study is to examine the association between the
      prescription of oral contraceptives and the incidence of chlamydia, and between
      the prescription of oral contraceptives and the number of abortions in a
      population-based ecological study. METHODS: For this study we used register data
      from the Swedish Institute for Infectious Disease Control (chlamydia incidence),
      the Swedish National Board of Health and Welfare (number of abortions),
      Statistics Sweden (population data), and Apoteket (Swedish pharmacy)
      (prescriptions for oral contraceptives). We conducted ordinary least squares
      regression analysis of the association between chlamydia or abortions and the
      prescription of oral contraceptives. RESULTS: The prescription of oral
      contraceptives has a positive association on both the incidence of chlamydia and
      the numbers of abortion. Our best model predicts that prescription of 100 yearly
      doses of oral contraceptives increase the abortions by 3.3 cases among 16-year
      old women and 0.7 cases among 29-year-old women, while cases of chlamydia
      increase by 6.7 among 16-year-old women and 1.5 among 29-year-old women.
      CONCLUSIONS: Our findings indicate that the use of oral contraceptives among
      young people and young adults is positively associated with the chlamydia
      incidence and the abortion rate in these populations in Sweden.

PMID- 21969329
TI  - Identifying fast-food restaurants using a central register as a measure of the
      food environment.
AB  - OBJECTIVE: To validate the identification and location of fast-food restaurants
      according to a government list of inspected food stores and restaurants. METHODS:
      Fast-food restaurants in the Capital Region of Denmark were identified using a
      government list of inspected food stores and restaurants (the Smiley register,
      spring 2010). Ground-truthing was used as the validation method and was performed
      in May and June 2010 in 125 randomly selected 250*250 m grid cells. RESULTS: A
      total of 186 fast-food restaurants was identified by ground-truthing and 99% of
      these were registered in the same grid cell by the Smiley register. However, only
      152 restaurants of these were categorised as fast-food restaurants by both
      methods. The sensitivity was 82% and the positive predictive value was 92%. The
      mean+/-standard deviation position accuracy was 15+/-24 m. CONCLUSIONS: Using a
      government list of inspected restaurants was found to be a valid and useful
      alternative to expensive and time-consuming field observation and provided a
      relatively accurate tool for identifying and locating fast-food restaurants in
      communities.

PMID- 21969330
TI  - Association between hand grip/body weight ratio and disability pension due to
      musculoskeletal disorders: a population-based cohort study of 1 million Swedish
      men.
AB  - AIMS: To investigate the predictive value of hand grip/body weight ratio and hand
      grip strength in early adulthood for obtaining a disability pension (DP) due to
      musculoskeletal disorders in later life. METHODS: A nationwide population-based
      sample of men born 1951-76 (n=1,387,166) in Sweden and anthropometric and
      strength indicators from their conscription examination. Register data on the
      date and diagnoses of granted DP between the years 1971-2006. Cox proportional
      hazards regression was used to estimate hazard ratios (HR) with 95% confidence
      intervals (95% CI). RESULTS: The lowest quintile of hand grip/body weight ratio
      predicted a greatly increased risk (HR 2.51, 95% CI 2.40-2.63) for DP due to
      musculoskeletal disorders compared to the mid-quintile. The highest quintile of
      hand grip/body weight ratio predicted a decreased risk (HR 0.80, 95% CI 0.75
      0.84). Stratification of the hand grip/body weight ratio with body mass index
      confirmed the results. However, the highest quintiles of hand grip strength
      adjusted for height and weight predicted a somewhat increased risk for DP due to
      musculoskeletal disorders (HR 1.25, 95% CI 1.18-1.32). CONCLUSIONS: This study
      indicates that the hand grip/body weight ratio in young adulthood is strongly and
      inversely associated with men's risk of obtaining a disability pension due to
      musculoskeletal disorders in later life. However, the risk seems to be mediated
      through the body weight. The properties of hand grip/body weight ratio should be
      further evaluated before it can be recommended for use in clinical and
      epidemiological studies.

PMID- 21969332
TI  - Importation of KPC-2-producing Escherichia coli from India.

PMID- 21969331
TI  - A cautionary case of microbial solidarity: concurrent isolation of VIM-1
      producing Klebsiella pneumoniae, Escherichia coli and Enterobacter cloacae from
      an infected wound.

PMID- 21969333
TI  - Characterization of qnr-positive Escherichia coli isolates from food-producing
      animals in the Netherlands.

PMID- 21969326
TI  - The significance of G protein-coupled receptor crystallography for drug
      discovery.
AB  - Crucial as molecular sensors for many vital physiological processes, seven
      transmembrane domain G protein-coupled receptors (GPCRs) comprise the largest
      family of proteins targeted by drug discovery. Together with structures of the
      prototypical GPCR rhodopsin, solved structures of other liganded GPCRs promise to
      provide insights into the structural basis of the superfamily's biochemical
      functions and assist in the development of new therapeutic modalities and drugs.
      One of the greatest technical and theoretical challenges to elucidating and
      exploiting structure-function relationships in these systems is the emerging
      concept of GPCR conformational flexibility and its cause-effect relationship for
      receptor-receptor and receptor-effector interactions. Such conformational changes
      can be subtle and triggered by relatively small binding energy effects, leading
      to full or partial efficacy in the activation or inactivation of the receptor
      system at large. Pharmacological dogma generally dictates that these changes
      manifest themselves through kinetic modulation of the receptor's G protein
      partners. Atomic resolution information derived from increasingly available
      receptor structures provides an entree to the understanding of these events and
      practically applying it to drug design. Supported by structure-activity
      relationship information arising from empirical screening, a unified structural
      model of GPCR activation/inactivation promises to both accelerate drug discovery
      in this field and improve our fundamental understanding of structure-based drug
      design in general. This review discusses fundamental problems that persist in
      drug design and GPCR structural determination.

PMID- 21969334
TI  - Genetic modification of the O-polysaccharide of Francisella tularensis results in
      an avirulent live attenuated vaccine.
AB  - BACKGROUND: Francisella tularensis, the causative agent of tularemia, is a highly
      virulent microbe. One significant virulence factor of F. tularensis is the O
      polysaccharide (O-PS) portion of the organism's lipopolysaccharide. METHODS: A
      wzy (O-antigen polymerase) deletion mutant of Ft. live attenuated vaccine strain
      (Ft.LVS), designated Ft.LVS::Deltawzy, was created and evaluated as a live
      attenuated vaccine. Specifically, the mutant's virulence potential and its
      protective efficacy against type A and type B strains were investigated by
      challenge of immunized mice. RESULTS: F. tularensis LVS::Deltawzy expressed only
      1 repeating unit of O-PS and yet, upon immunization, induced O-PS-specific
      antibodies. Compared with Ft.LVS, the mutant was highly sensitive to complement
      mediated lysis, significantly attenuated in virulence, and was recovered in much
      lower numbers from the organs of infected mice. Intranasal immunization with
      Ft.LVS::Deltawzy provided protection against subsequent intranasal infection with
      the highly virulent type A strain SchuS4 and with Ft.LVS. Immunization with
      Ft.LVS::Deltawzy elicited both humoral and cell-mediated immunity. CONCLUSIONS:
      Ft.LVS::Deltawzy was avirulent in mice and, despite expressing only 1 repeating
      unit of the O-PS, induced antibodies to the full-length O-PS. Vaccination with
      Ft.LVS::Deltawzy protected mice against intranasal challenge with both type A and
      type B strains of F. tularensis and induced functional immunity through both
      humoral and cellular mechanisms.

PMID- 21969327
TI  - alpha6beta2* and alpha4beta2* nicotinic acetylcholine receptors as drug targets
      for Parkinson's disease.
AB  - Parkinson's disease is a debilitating movement disorder characterized by a
      generalized dysfunction of the nervous system, with a particularly prominent
      decline in the nigrostriatal dopaminergic pathway. Although there is currently no
      cure, drugs targeting the dopaminergic system provide major symptomatic relief.
      As well, agents directed to other neurotransmitter systems are of therapeutic
      benefit. Such drugs may act by directly improving functional deficits in these
      other systems, or they may restore aberrant motor activity that arises as a
      result of a dopaminergic imbalance. Recent research attention has focused on a
      role for drugs targeting the nicotinic cholinergic systems. The rationale for
      such work stems from basic research findings that there is an extensive overlap
      in the organization and function of the nicotinic cholinergic and dopaminergic
      systems in the basal ganglia. In addition, nicotinic acetylcholine receptor
      (nAChR) drugs could have clinical potential for Parkinson's disease. Evidence for
      this proposition stems from studies with experimental animal models showing that
      nicotine protects against neurotoxin-induced nigrostriatal damage and improves
      motor complications associated with l-DOPA, the "gold standard" for Parkinson's
      disease treatment. Nicotine interacts with multiple central nervous system
      receptors to generate therapeutic responses but also produces side effects. It is
      important therefore to identify the nAChR subtypes most beneficial for treating
      Parkinson's disease. Here we review nAChRs with particular emphasis on the
      subtypes that contribute to basal ganglia function. Accumulating evidence
      suggests that drugs targeting alpha6beta2* and alpha4beta2* nAChR may prove
      useful in the management of Parkinson's disease.

PMID- 21969336
TI  - De novo copy number variants associated with intellectual disability have a
      paternal origin and age bias.
AB  - BACKGROUND: De novo mutations and structural rearrangements are a common cause of
      intellectual disability (ID) and other disorders with reduced or null
      reproductive fitness. Insight into the genomic and environmental factors
      predisposing to the generation of these de novo events is therefore of
      significant clinical importance. METHODS: This study used information from single
      nucleotide polymorphism microarrays to determine the parent-of-origin of 118 rare
      de novo copy number variations (CNVs) detected in a cohort of 3443 patients with
      ID. RESULTS: The large majority of these CNVs (76%, p=1.14*10(-8)) originated on
      the paternal allele. This paternal bias was independent of CNV length and CNV
      type. Interestingly, the paternal bias was less pronounced for CNVs flanked by
      segmental duplications (64%), suggesting that molecular mechanisms involved in
      the formation of rare de novo CNVs may be dependent on the parent-of-origin. In
      addition, a significantly increased paternal age was only observed for those CNVs
      which were not flanked by segmental duplications (p=0.02). CONCLUSION: This
      indicates that rare de novo CNVs are increasingly being generated with advanced
      paternal age by replication based mechanisms during spermatogenesis.

PMID- 21969335
TI  - Dendritic cell dysfunction during primary HIV-1 infection.
AB  - Dendritic cells have critical roles for generating and fine-tuning adaptive
      immune responses and for regulating immune activity through cytokine secretion.
      In this study, we analyzed functional properties of dendritic cells in primary
      human immunodeficiency virus type 1 (HIV-1) infection. We found substantial
      disarray of the functional properties of myeloid and plasmacytoid dendritic cells
      in acute HIV-1 infection, which included defective antigen-presenting and
      cytokine secretion properties and was associated with a distinct surface
      expression profile of immunomodulatory dendritic cell receptors from the
      leukocyte immunoglobulin-like receptor family. These data indicate that key
      functional properties of dendritic cells are compromised during primary HIV-1
      infection.

PMID- 21969337
TI  - Genetic diagnosis of Duchenne and Becker muscular dystrophy using next-generation
      sequencing technology: comprehensive mutational search in a single platform.
AB  - BACKGROUND: Duchenne muscular dystrophy or Becker muscular dystrophy might be a
      suitable candidate disease for application of next-generation sequencing in the
      genetic diagnosis because the complex mutational spectrum and the large size of
      the dystrophin gene require two or more analytical methods and have a high cost.
      The authors tested whether large deletions/duplications or small mutations, such
      as point mutations or short insertions/deletions of the dystrophin gene, could be
      predicted accurately in a single platform using next-generation sequencing
      technology. METHODS: A custom solution-based target enrichment kit was designed
      to capture whole genomic regions of the dystrophin gene and other muscular
      dystrophy-related genes. A multiplexing strategy, wherein four differently bar
      coded samples were captured and sequenced together in a single lane of the
      Illumina Genome Analyser, was applied. The study subjects were 25 PATIENTS: 16
      with deficient dystrophin expression without a large deletion/duplication and 9
      with a known large deletion/duplication. RESULTS: Nearly 100% of the exonic
      region of the dystrophin gene was covered by at least eight reads with a mean
      read depth of 107. Pathogenic small mutations were identified in 15 of the 16
      patients without a large deletion/duplication. Using these 16 patients as the
      standard, the authors' method accurately predicted the deleted or duplicated
      exons in the 9 patients with known mutations. Inclusion of non-coding regions and
      paired-end sequence analysis enabled accurate identification by increasing the
      read depth and providing information about the breakpoint junction. CONCLUSIONS:
      The current method has an advantage for the genetic diagnosis of Duchenne
      muscular dystrophy and Becker muscular dystrophy wherein a comprehensive
      mutational search may be feasible using a single platform.

PMID- 21969338
TI  - Plastic bag method for active sample loading into transmission electron
      microscope.
AB  - A plastic bag method was developed to observe air-sensitive samples on
      microstructure and phase distribution without exposure to air during the holder
      transfer process into the transmission electron microscope (TEM). As an example,
      a type of lithium aluminum hydride (Li(3)AlH(6)) was observed in the TEM to
      demonstrate the effectiveness of this method. Results show that the plastic bag
      method is a simple and practical TEM transfer method utilized to reduce air
      contact for a series of air-sensitive materials.

PMID- 21969339
TI  - Re: Long-term outcomes of invasive ipsilateral breast tumor recurrences after
      lumpectomy in NSABP B-17 and B-24 randomized clinical trials for DCIS.

PMID- 21969340
TI  - A prospective evaluation of a protocol for magnetic resonance imaging of patients
      with implanted cardiac devices.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) is avoided in most patients with
      implanted cardiac devices because of safety concerns. OBJECTIVE: To define the
      safety of a protocol for MRI at the commonly used magnetic strength of 1.5 T in
      patients with implanted cardiac devices. DESIGN: Prospective nonrandomized trial.
      (ClinicalTrials.gov registration number: NCT01130896) SETTING: One center in the
      United States (94% of examinations) and one in Israel. PATIENTS: 438 patients
      with devices (54% with pacemakers and 46% with defibrillators) who underwent 555
      MRI studies. INTERVENTION: Pacing mode was changed to asynchronous for pacemaker
      dependent patients and to demand for others. Tachyarrhythmia functions were
      disabled. Blood pressure, electrocardiography, oximetry, and symptoms were
      monitored by a nurse with experience in cardiac life support and device
      programming who had immediate backup from an electrophysiologist. MEASUREMENTS:
      Activation or inhibition of pacing, symptoms, and device variables. RESULTS: In 3
      patients (0.7% [95% CI, 0% to 1.5%]), the device reverted to a transient back-up
      programming mode without long-term effects. Right ventricular (RV) sensing
      (median change, 0 mV [interquartile range {IQR}, -0.7 to 0 V]) and atrial and
      right and left ventricular lead impedances (median change, -2 Omega [IQR, -13 to
      0 Omega], -4 Omega [IQR, -16 to 0 Omega], and -11 Omega [IQR, -40 to 0 Omega],
      respectively) were reduced immediately after MRI. At long-term follow-up (61% of
      patients), decreased RV sensing (median, 0 mV, [IQR, -1.1 to 0.3 mV]), decreased
      RV lead impedance (median, -3 Omega, [IQR, -29 to 15 Omega]), increased RV
      capture threshold (median, 0 V, IQR, [0 to 0.2 Omega]), and decreased battery
      voltage (median, -0.01 V, IQR, -0.04 to 0 V) were noted. The observed changes did
      not require device revision or reprogramming. LIMITATIONS: Not all available
      cardiac devices have been tested. Long-term in-person or telephone follow-up was
      unavailable in 43 patients (10%), and some data were missing. Those with missing
      long-term capture threshold data had higher baseline right atrial and right
      ventricular capture thresholds and were more likely to have undergone thoracic
      imaging. Defibrillation threshold testing and random assignment to a control
      group were not performed. CONCLUSION: With appropriate precautions, MRI can be
      done safely in patients with selected cardiac devices. Because changes in device
      variables and programming may occur, electrophysiologic monitoring during MRI is
      essential.

PMID- 21969341
TI  - Pentraxin-3 as a marker of disease activity in Takayasu arteritis.
AB  - BACKGROUND: Because pentraxin-3 (PTX3) is produced by immune and vascular cells
      in response to proinflammatory signals, it may be a useful biomarker for defining
      disease activity in patients with Takayasu arteritis. OBJECTIVE: To compare PTX3
      levels in patients who have Takayasu arteritis with those in healthy and infected
      controls, and to compare accuracy of PTX3 levels with that of C-reactive protein
      (CRP) levels and erythrocyte sedimentation rate (ESR) for distinguishing active
      and inactive disease. DESIGN: Cross-sectional, noninterventional study conducted
      between September 2005 and October 2008. SETTING: Immunology and rheumatology
      clinic at a university hospital in Italy. PATIENTS: 57 consecutive patients with
      Takayasu arteritis and known disease activity, 57 healthy blood donor controls,
      and 15 patients with acute infection. MEASUREMENTS: Disease activity by clinical
      criteria; plasma PTX3 and CRP levels and ESR. RESULTS: 27 patients had active
      Takayasu arteritis; 30 had inactive disease. Levels of PTX3 were higher in
      patients with active disease (median, >2.14 ng/mL [range, 0.57 to 48.18 ng/mL])
      than in those with inactive disease (median, 0.63 ng/mL [range, 0.00 to 1.64
      ng/mL]) and were higher than in healthy patients (median, 0.11 ng/mL [range, 0 to
      1.20 ng/mL]) or those with acute infection (median, 0.26 ng/mL [range, 0 to 0.75
      ng/mL]). A plasma PTX3 level greater than 1 ng/mL was more accurate than normal
      thresholds of CRP or ESR for distinguishing active from inactive disease.
      LIMITATION: The study excluded patients with unknown or equivocal disease status.
      CONCLUSION: Plasma levels of PTX3 could help distinguish active from inactive
      Takayasu arteritis but should not be adopted for clinical use until the findings
      are confirmed in a broader spectrum of patients whose disease activity is unknown
      or equivocal before testing.

PMID- 21969342
TI  - Effectiveness of primary care-relevant treatments for obesity in adults: a
      systematic evidence review for the U.S. Preventive Services Task Force.
AB  - BACKGROUND: Overweight and obesity in adults are common and adversely affect
      health. PURPOSE: To summarize effectiveness and harms of primary care-relevant
      weight-loss interventions for overweight and obese adults. DATA SOURCES: MEDLINE,
      Cochrane Central Register of Controlled Trials, and PsycINFO from January 2005 to
      September 2010; systematic reviews for identifying trials before 2005. STUDY
      SELECTION: Two investigators appraised 6498 abstracts and 648 articles. Clinical
      trials were included if control groups received minimal interventions. Articles
      were rated as good, fair, or poor by using design-specific criteria. DATA
      EXTRACTION: One investigator abstracted study characteristics and findings for
      good- and fair-quality studies; a second checked them. DATA SYNTHESIS:
      Behaviorally based treatment resulted in 3-kg (6.6-lb) greater weight loss in
      intervention than control participants after 12 to 18 months, with more treatment
      sessions associated with greater loss. Limited data suggest weight-loss
      maintenance for 1 year or more. Orlistat plus behavioral intervention resulted in
      3-kg (6.6-lb) more weight loss than did placebo after 12 months. Metformin
      resulted in less weight loss. Data on effects of weight-loss treatment on long
      term health outcomes (for example, death and cardiovascular disease) were
      insufficient. Weight-loss treatment reduced diabetes incidence in participants
      with prediabetes. Effects on intermediate outcomes (for example, lipids and blood
      pressure) were mixed and small. Data on serious medication harms were
      insufficient. Medications commonly caused withdrawals due to gastrointestinal
      symptoms. LIMITATIONS: Few studies reported health outcomes. Behaviorally based
      treatments were heterogeneous and specific elements were not well-described. Many
      studies could not be pooled because of insufficient reporting of variance data.
      Medication trials had high attrition, lacked postdiscontinuation data, and were
      inadequately powered for rare adverse effects. CONCLUSION: Behaviorally based
      treatments are safe and effective for weight loss and maintenance. PRIMARY
      FUNDING SOURCE: Agency for Healthcare Research and Quality.

PMID- 21969343
TI  - Clinical decision rules for excluding pulmonary embolism: a meta-analysis.
AB  - BACKGROUND: Clinical probability assessment is combined with d-dimer testing to
      exclude pulmonary embolism (PE). PURPOSE: To compare the test characteristics of
      gestalt (a physician's unstructured estimate) and clinical decision rules for
      evaluating adults with suspected PE and assess the failure rate of gestalt and
      rules when used in combination with d-dimer testing. DATA SOURCES: Articles in
      MEDLINE and EMBASE in English, French, German, Italian, Spanish, or Dutch that
      were published between 1966 and June 2011. STUDY SELECTION: 3 reviewers, working
      in pairs, selected prospective studies in consecutive patients suspected of
      having PE. Studies had to estimate the probability of PE by using gestalt or a
      decision rule and verify the diagnosis by using an appropriate reference
      standard. DATA EXTRACTION: Data on study characteristics, test performance, and
      prevalence were extracted. Reviewers constructed 2 * 2 tables and assessed the
      methodological quality of the studies. DATA SYNTHESIS: 52 studies, comprising 55
      268 patients, were selected. Meta-analysis was performed on studies that used
      gestalt (15 studies; sensitivity, 0.85; specificity, 0.51), the Wells rule with a
      cutoff value less than 2 (19 studies; sensitivity, 0.84; specificity, 0.58) or 4
      or less (11 studies; sensitivity, 0.60; specificity, 0.80), the Geneva rule (5
      studies; sensitivity, 0.84; specificity, 0.50), and the revised Geneva rule (4
      studies; sensitivity, 0.91; specificity, 0.37). An increased prevalence of PE was
      associated with higher sensitivity and lower specificity. Combining a decision
      rule or gestalt with d-dimer testing seemed safe for all strategies, except when
      the less-sensitive Wells rule (cutoff value <=4) was combined with less-sensitive
      qualitative d-dimer testing. LIMITATIONS: Studies had substantial heterogeneity
      due to prevalence of PE and differences in threshold. Many studies (63%) had
      potential bias due to differential disease verification. CONCLUSION: Clinical
      decision rules and gestalt can safely exclude PE when combined with sensitive d
      dimer testing. The authors recommend standardized rules because gestalt has lower
      specificity, but the choice of a particular rule and d-dimer test depend on both
      prevalence and setting.

PMID- 21969344
TI  - Threats to graduate medical education funding and the need for a rational
      approach: a statement from the alliance for academic internal medicine.
AB  - With the current focus on reducing the federal budget deficit, funding for
      graduate medical education (GME) has come under scrutiny, particularly those
      monies labeled as indirect medical education payments; these are intended to
      cover ill-defined costs inherent to training programs, such as increased lengths
      of stay, additional testing, and patients with more complex conditions. Although
      there are cogent arguments that indirect medical education expenses have
      decreased over the past 25 years, there is also a reasonable expectation that
      direct medical education expenses, such as those related to resident salaries,
      faculty involvement, administration of programs, and overhead costs, have
      increased. Our current system of GME financing is complex and cumbersome and
      relies almost exclusively on government support. This article examines the
      adequacy of current funding, focusing on the economics of the entire system
      rather than individual hospitals, states, or regions. It also recommends
      reexamining GME financing and considering options that ensure appropriate levels
      of government support and participation of other health care insurers to
      adequately fund GME.

PMID- 21969345
TI  - Commissioning health care in England: an evolving story.
AB  - The general election in the United Kingdom in May 2010 resulted in the election
      of a new government, a coalition between Conservative and Liberal Democrat
      parties. Six weeks after the election, a white paper, "Equity and Excellence:
      Liberating the NHS," that proposed profound changes to the structure and
      organization of the health service was published. The change that generated the
      most discussion was the proposal that general practitioners be placed at the
      center of the system and given control of about 80% of the National Health
      Service's L100 billion budget. The proposals were greeted with considerable
      concern by many health care professionals, patient representatives, and the
      media. In response, the government organized an independent review, and proposals
      have been altered in response. This article outlines the current organization of
      the National Health Service, the rationale for change, and government proposals.

PMID- 21969346
TI  - Magnetic resonance imaging and cardiac devices: how safe is safe enough?

PMID- 21969347
TI  - A little hyponatremic.

PMID- 21969348
TI  - One thousand and one nights.

PMID- 21969349
TI  - Perioperative myocardial infarction in patients undergoing noncardiac surgery.

PMID- 21969350
TI  - Discordant thymectomy in identical twins concordant for myasthenia gravis.
AB  - BACKGROUND: Thymectomy is standard therapy fornonthymomatousmyasthenia gravis
      despite the absence of randomized clinical trials (1). Myasthenia gravis is
      uncommonly reported in monozygous twins; disease concordance occurs in
      approximately one third of such identical twin pairs; and treatment for
      myasthenia gravis, when described,is usually concordant in identical twin pairs
      (2). OBJECTIVE: To report an 11-year clinical course of a pair of identical twins
      concordant for generalized acetylcholine receptor antibody-positive
      nonthymomatous myasthenia gravis in whom only 1 was treated with extended
      transsternal thymectomy. CASE REPORT: Twin A was a 19-year-old white woman who
      presented with an 8-week history of intermittent leg weakness, causing her to
      fall during activities, such as climbing stairs. On examination,she had
      moderately severe fatigable proximal muscle weakness and ptosis. Her weakness
      improved with intravenous edrophonium administration.Initial binding
      acetylcholine receptor antibody titer was 1.22 nmol/L (normal value, 0.03
      nmol/L). Repetitive 2-Hz nerve(median, ulnar, and facial) stimulation studies
      demonstrated up to a 16% decremental response. Chest computed tomography showed
      residual thymic tissue without thymoma. An extended transsternal thymectomy was
      performed 11 weeks after the onset of symptoms.

PMID- 21969351
TI  - Treatment of chronic hepatitis E in a patient with HIV infection.
AB  - BACKGROUND: Hepatitis E virus (HEV) infections in immunosuppressed patients can
      result in chronic hepatitis that rapidly progresses to cirrhosis (1, 2). When
      immunosuppressed transplant recipients are treated with pegylated -interferon and
      ribavirin, HEV clears and liver histology improves (2). However, we are not aware
      of reports about how this therapy works in patients with HIV infection.
      OBJECTIVE: To describe the clinical and laboratory response to antiviral therapy
      for chronic HEV infection in a patient also infected with HIV. CASE REPORT: We
      studied a 48-year-old bisexual male with HIV- 1 infection who was chronically
      infected with HEV genotype 3a and had several years of painful sensory neuropathy
      of uncertain cause in the lower limbs (3). He had malaise, persistently abnormal
      liver function tests, and active inflammation and cirrhosis on liver biopsy
      (Figure).Before beginning anti-HEV therapy, the patient had an undetectable HIV
      viral load and a CD4 cell count between 30 and 150 cells/mL for the previous 2
      years while receiving combination antiretroviral therapy (abacavir-lamivudine
      once daily and lopinavir-ritonavir twice daily).

PMID- 21969352
TI  - Summaries for patients. The safety of magnetic resonance imaging in patients with
      pacemakers or defibrillators.

PMID- 21969353
TI  - In the clinic. Management of newly diagnosed HIV infection.
AB  - This issue provides a clinical overview of management of newly diagnosed HIV
      infection focusing on prevention, diagnosis, treatment, practice improvement, and
      patient information. Readers can complete the accompanying CME quiz for 1.5
      credits. Only ACP members and individual subscribers can access the electronic
      features of In the Clinic. Non-subscribers who wish to access this issue of In
      the Clinic can elect "Pay for View." Subscribers can receive 1.5 category 1 CME
      credits by completing the CME quiz that accompanies this issue of In the Clinic.
      The content of In the Clinic is drawn from the clinical information and education
      resources of the American College of Physicians (ACP), including PIER
      (Physicians' Information and Education Resource) and MKSAP (Medical Knowledge and
      Self Assessment Program). Annals of Internal Medicine editors develop In the
      Clinic from these primary sources in collaboration with the ACP's Medical
      Education and Publishing division and with assistance of science writers and
      physician writers. Editorial consultants from PIER and MKSAP provide expert
      review of the content. Readers who are interested in these primary resources for
      more detail can consult www.acponline.org, http://pier.acponline.org, and other
      resources referenced within each issue of In the Clinic.

PMID- 21969354
TI  - Evaluation of mouse tail-vein injections both qualitatively and quantitatively on
      small-animal PET tail scans.
AB  - Quantitative small-animal PET of mice requires successful delivery of
      radiotracers into the venous system. Intravenous injection of radiotracers via
      lateral tail veins is the most commonly used method of administration and can be
      technically challenging. Evaluation of the quality of an intravenous injection is
      necessary to determine whether small-animal PET is quantitatively accurate. The
      purpose of this study was to evaluate and compare the quality of 50 consecutive
      intravenous injections into mouse tail veins using both quantitative and
      qualitative methods. METHODS: During (18)F-FDG intravenous injection, qualitative
      assessment of the injection was performed and classified according to specific
      criteria as good, intermediate, or poor. Small-animal PET scans of the body and
      tail were acquired, and tail injection sites were quantitatively assessed in
      terms of percentage injected dose per gram and classified as low, medium, or high
      uptake of (18)F-FDG. Qualitative and quantitative methods were compared. To
      assess baseline amounts of (18)F-FDG in the tail without a tail injection, 3
      additional mice were injected by the intraperitoneal method, imaged, and
      quantitatively assessed in the same manner. The in vivo imaging data were
      validated on 7 additional mice by sacrificing them after scans, removing their
      tails, rescanning the tails, and then measuring the tail radioactivity ex vivo in
      a gamma-counter and correlating it with the in vivo amount. RESULTS: Validation
      of in vivo imaging to ex vivo data yielded an excellent correlation, with an r(2)
      value of 0.95. Comparison of qualitative and quantitative methods yielded 45
      matching results (42 good and low, 2 intermediate and medium, and 1 poor and
      high). There were 5 cases of mismatching results (1 false-negative and 4 false
      positive) between qualitative and quantitative methods. Low-uptake tail
      injections were comparable to the intraperitoneal injection values. Using
      qualitative methods, accuracy was true 90% (45/50) of the time. The overall rate
      of successful intravenous injections was 92% (46/50) using quantitative methods.
      CONCLUSION: Qualitative assessment is all that is necessary if the intravenous
      injection is classified as good. In intermediate, poor, or uncertain
      classifications, a scan of the tail should be performed for quantitative
      assessment.

PMID- 21969355
TI  - Selective polarographic determination of stannous ion in technetium
      radiopharmaceutical cold kits.
AB  - The aim of this work was to develop a selective method for quantification of
      Sn(II) and Sn(IV) in dimercaptosuccinic acid (DMSA), ethylcysteinate dimer (ECD),
      methylenediphosphonic acid (MDP), and pyrophosphate radiopharmaceutical cold kits
      by differential pulse polarography. METHODS: A dripping mercury electrode 150
      polarographic/stripping analyzer with a conventional 3-electrode configuration
      was used with 3 M H(2)SO(4) and 3 M HCl supporting electrolytes for Sn(II) and
      Sn(IV), respectively. The polarographic analysis was performed using a 1-s drop
      time, 50-mV.s(-1) scan rate, -50-mV pulse amplitude, 40-ms pulse time, and 10-mV
      step amplitude. To quantify Sn(IV), oxidation of Sn(II) by H(2)O(2) was
      performed. The calibration curves for Sn(II) and Sn(IV) were obtained in the
      range of 0-10 MUg.mL(-1). RESULTS: The analytic curves for Sn(II) in 3 M
      H(2)SO(4) and Sn(IV) in 3 M HCl were represented by the following equations: i
      (MUA) = 0.098 [Sn(II)] + 0.018 (r(2) = 0.998) and i (MUA) = 0.092 [Sn(IV)] +
      0.016 (r(2) = 0.998), respectively. The detection limits were 0.21 MUg.mL(-1) for
      Sn(II) and 0.15 MUg.mL(-1) for Sn(IV). In DMSA, ECD, MDP, and pyrophosphate,
      90.0%, 64.9%, 93.2%, and 87.5%, respectively, of the tin was present as Sn(II).
      In this work, selective determination of Sn(II) and Sn(IV) was achieved using 2
      supporting electrolytes (H(2)SO(4) and HCl). In 3 M H(2)SO(4), only Sn(II)
      produced a polarographic wave with the maximum current in -370 mV. Under the same
      conditions, no current could be determined for Sn(IV). In 3 M HCl, Sn(II) and
      Sn(IV) were electroactive and the maximum currents of the 2 waves appeared in 
      250 and -470 mV. No other components of the lyophilized reagents had any
      influence. CONCLUSION: The developed polarographic method was adequate to
      quantify Sn(II) and Sn(IV) in DMSA, ECD, MDP, and pyrophosphate cold kits.

PMID- 21969356
TI  - Risk stratification in heart failure using 123I-MIBG.
AB  - Heart failure is a progressive, heterogeneous form of cardiovascular disease that
      requires treatment to be individualized depending on the presenting symptoms. A
      decision to use an implantable cardioverter-defibrillator (ICD) is based on
      chronic heart failure patients presenting with a New York Heart Association
      classification of II or III and a left ventricular ejection fraction (LVEF) less
      than or equal to 30%-35%. A large percentage of ICD devices, however, never
      deliver therapy during their lifetime, and as many as 33% of patients ineligible
      for an ICD (LVEF > 35%) die of sudden cardiac death. (123)I
      metaiodobenzylguanidine ((123)I-MIBG) scintigraphy identifies sympathetic nervous
      system dysfunction and has been shown to lead to better patient stratification.
      This article reviews the role of planar (123)I-MIBG global quantitation in
      improving differentiation of heart failure, regardless of the LVEF, to better
      identify those in whom an ICD is more likely to reap benefits. It goes on to
      explore the potential incremental benefit of SPECT-based regional quantitation to
      risk stratification and provides a case example in which (123)I-MIBG SPECT was
      used to inform a decision to not use an ICD in a patient eligible under the
      standard criteria.

PMID- 21969357
TI  - National Electrical Manufacturers Association NU-4 performance evaluation of the
      PET component of the NanoPET/CT preclinical PET/CT scanner.
AB  - The NanoPET/CT represents the latest generation of commercial preclinical PET/CT
      systems. This article presents a performance evaluation of the PET component of
      the system according to the National Electrical Manufacturers Association (NEMA)
      NU-4 2008 standard. METHODS: The NanoPET/CT consists of 12 lutetium yttrium
      orthosilicate:cerium modular detectors forming 1 ring, with 9.5-cm axial coverage
      and a 16-cm animal port. Each detector crystal is 1.12 * 1.12 * 13 mm, and 1
      module contains 81 * 39 of these crystals. An optical light guide transmits the
      scintillation light to the flat-panel multianode position-sensitive
      photomultiplier tubes. Analog-to-digital converter cards and a field-programmable
      gate array-based data-collecting card provide the readout. Spatial resolution,
      sensitivity, counting rate capabilities, and image quality were evaluated in
      accordance with the NEMA NU-4 standard. Energy and temporal resolution
      measurements and a mouse imaging study were performed in addition to the
      standard. RESULTS: Energy resolution was 19% at 511 keV. The spatial resolution,
      measured as full width at half maximum on single-slice rebinning/filtered
      backprojection-reconstructed images, approached 1 mm on the axis and remained
      below 2.5 mm in the central 5-cm transaxial region both in the axial center and
      at one-quarter field of view. The maximum absolute sensitivity for a point source
      at the center of the field of view was 7.7%. The maximum noise equivalent
      counting rates were 430 kcps at 36 MBq and 130 kcps at 27 MBq for the mouse- and
      rat-sized phantoms, respectively. The uniformity and recovery coefficients were
      measured with the image-quality phantom, giving good-quality images. In a mouse
      study with an (18)F-labeled thyroid-specific tracer, the 2 lobes of the thyroid
      were clearly distinguishable, despite the small size of this organ. The flexible
      readout system allowed experiments to be performed in an efficient manner, and
      the system remained stable throughout. CONCLUSION: The large number of detector
      crystals, arranged with a fine pitch, results in excellent spatial resolution,
      which is the best reported for currently available commercial systems. The
      absolute sensitivity is high over the field of view. Combined with the excellent
      image quality, these features make the NanoPET/CT a powerful tool for preclinical
      research.

PMID- 21969359
TI  - The importance of food.

PMID- 21969358
TI  - Atherosclerosis plaque heterogeneity and response to therapy detected by in vivo
      molecular imaging of matrix metalloproteinase activation.
AB  - Matrix metalloproteinases (MMPs) play a key role in the development of
      atherosclerosis and its complications. In vivo detection and quantification of
      MMP activation can help track the propensity to complications and response to
      therapy. We sought to establish an in vivo imaging approach for monitoring MMP
      activation in atherosclerotic mouse aorta and use it to assess the response to
      dietary modification. METHOD: Apolipoprotein-deficient mice were fed normal chow
      or a high-fat diet (HFD) for up to 3 mo or a HFD for 2 mo, followed by 1 mo on
      normal chow. Then they underwent micro-SPECT/CT, along with autoradiography and
      oil red O staining of tissues. RESULTS: After 3 mo of HFD, there was considerable
      atherosclerosis in the aorta. In vivo micro-SPECT/CT using RP782 (an (111)In
      labeled tracer targeting activated MMPs) showed a heterogeneous pattern of tracer
      uptake along the aorta. Heterogeneity of RP782 uptake was confirmed by
      autoradiography, and specificity was demonstrated using excess unlabeled
      precursor. Tracer uptake quantified by micro-SPECT significantly correlated with
      uptake quantified by autoradiography. Comparison of oil red O staining with
      autoradiography demonstrated areas of discordance between plaque presence and
      tracer uptake. HFD withdrawal led to significant reduction in RP782 uptake beyond
      the effect on plaque area. MMP expression and macrophage infiltration were
      similarly heterogeneous along the aorta and significantly reduced after
      withdrawal from the HFD. Finally, RP782 uptake significantly correlated with
      aortic macrophage content. CONCLUSION: Molecular imaging of MMP activation
      reveals the heterogeneity of atherosclerotic plaques and is a useful tool for
      tracking plaque biology and response to therapy.

PMID- 21969360
TI  - Associations between displayed alcohol references on Facebook and problem
      drinking among college students.
AB  - OBJECTIVE: To examine the associations between displayed alcohol use and
      intoxication/problem drinking (I/PD) references on Facebook and self-reported
      problem drinking using a clinical scale. DESIGN: Content analysis and cross
      sectional survey. SETTING: Facebook Web site (http://www.facebook.com/).
      PARTICIPANTS: The study included undergraduate students (age range, 18-20 years)
      at 2 state universities with public Facebook profiles. MAIN EXPOSURES: The
      profiles were categorized into 1 of 3 distinct categories: Nondisplayers, Alcohol
      Displayers, and I/PD Displayers. OUTCOME MEASURES: An online survey measured
      problem drinking using the Alcohol Use Disorders Identification Test (AUDIT)
      scale. Analyses examined associations between alcohol display category and (1)
      AUDIT problem drinking category using logistic regression, (2) AUDIT score using
      negative binomial regression, and (3) alcohol-related injury using the Fisher
      exact test. RESULTS: Among 307 profiles identified, 224 participants completed
      the survey (73% response rate). The average age was 18.8 years; 122 (54%) were
      female; 152 (68%) were white; and approximately 50% were from each university.
      Profile owners who displayed I/PD were more likely (odds ratio, 4.4; 95% CI, 2.0
      9.4) to score in the problem drinking category of the AUDIT scale, had 64.0%
      (incidence rate ratio, 1.64; 95% CI, 1.27-11.0) higher AUDIT scores overall, and
      were more likely to report an alcohol-related injury in the past year (P = .002).
      CONCLUSIONS: Displayed references to I/PD were positively associated with AUDIT
      scores suggesting problem drinking as well as alcohol-related injury. Results
      suggest that clinical criteria for problem drinking can be applied to Facebook
      alcohol references.

PMID- 21969361
TI  - Reduced risks of neural tube defects and orofacial clefts with higher diet
      quality.
AB  - OBJECTIVE: To examine whether better maternal diet quality was associated with
      reduced risk for selected birth defects. DESIGN: A multicenter, population-based
      case-control study, the National Birth Defects Prevention Study. SETTING: Ten
      participating centers in the United States. PARTICIPANTS: Eligible subjects'
      estimated due dates were from October 1997 through December 2005. Telephone
      interviews were conducted with 72% of case and 67% of control mothers. Analyses
      included 936 cases with neural tube defects (NTDs), 2475 with orofacial clefts,
      and 6147 nonmalformed controls. MAIN EXPOSURES: Food-frequency data were used to
      calculate the Mediterranean Diet Score (MDS) and Diet Quality Index (DQI),
      modeled after existing indices. MAIN OUTCOME MEASURE: Adjusted odds ratios (ORs).
      RESULTS: After covariate adjustment, increasing diet quality based on either
      index was associated with reduced risks for the birth defects studied. The
      strongest association was between anencephaly and DQI; the OR for highest vs
      lowest quartile was 0.49 (95% CI, 0.31-0.75). The ORs for cleft lip with or
      without cleft palate and cleft palate and DQI were also notable (0.66 [95% CI,
      0.54-0.81] and 0.74 [95%CI, 0.56-0.96], respectively). CONCLUSIONS: Healthier
      maternal dietary patterns, as measured by diet quality scores, were associated
      with reduced risks of NTDs and clefts. These results suggest that dietary
      approaches could lead to further reduction in risks of major birth defects and
      complement existing efforts to fortify foods and encourage periconceptional
      multivitamin use.

PMID- 21969362
TI  - Sustained decreases in risk exposure and youth problem behaviors after
      installation of the Communities That Care prevention system in a randomized
      trial.
AB  - OBJECTIVE: To test whether the Communities That Care (CTC) prevention system
      reduced levels of risk and adolescent problem behaviors community-wide 6 years
      after installation of CTC and 1 year after study-provided resources ended.
      DESIGN: A community randomized trial. SETTING: Twenty-four small towns in 7
      states, matched within state, randomly assigned to control or intervention
      condition in 2003. PARTICIPANTS: A panel of 4407 fifth-grade students was
      surveyed annually through 10th grade from 2004 to 2009. INTERVENTION: A coalition
      of community stakeholders received training and technical assistance to install
      CTC, used epidemiologic data to identify elevated risk factors and depressed
      protective factors in the community, and implemented programs to address their
      community's elevated risks from a menu of tested and effective programs for
      youths aged 10 to 14 years, their families, and schools. OUTCOME MEASURES: Levels
      of risk and incidence and prevalence of tobacco, alcohol, and other drug use;
      delinquency; and violent behavior by grade 10. RESULTS: Mean levels of targeted
      risks increased less rapidly between grades 5 and 10 in CTC than in control
      communities and were significantly lower in CTC than control communities in grade
      10. The incidence of delinquent behavior, alcohol use, and cigarette use and the
      prevalence of current cigarette use and past-year delinquent and violent behavior
      were significantly lower in CTC than in control communities in grade 10.
      CONCLUSIONS: Using the CTC system can produce enduring reductions in community
      wide levels of risk factors and problem behaviors among adolescents beyond the
      years of supported implementation, potentially contributing to long-term public
      health benefits. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01088542.

PMID- 21969363
TI  - Effects of a family intervention in reducing HIV risk behaviors among high-risk
      Hispanic adolescents: a randomized controlled trial.
AB  - OBJECTIVE: To determine the efficacy of a family intervention in reducing human
      immunodeficiency virus (HIV) risk behaviors among Hispanic delinquent
      adolescents. DESIGN: Randomized controlled trial. SETTING: Miami-Dade County
      Public School System and Miami-Dade County's Department of Juvenile Services,
      Florida. PARTICIPANTS: A total of 242 Hispanic delinquent youth aged 12 to 17
      years and their primary caregivers completed outcome assessments at baseline and
      3 months after intervention. INTERVENTION: Participants were randomized to either
      Familias Unidas (120 participants), a Hispanic-specific, family intervention
      designed to reduce HIV risk behaviors among Hispanic youth, or a community
      practice control condition (122 participants). MAIN OUTCOME MEASURES: Self
      reported measures included unprotected sexual behavior, engaging in sex while
      under the influence of alcohol and/or drugs, number of sexual partners, and
      incidence of sexually transmitted diseases. Family functioning (eg, parent
      adolescent communication, positive parenting, and parental monitoring) was also
      assessed via self-report measures. RESULTS: Compared with community practice,
      Familias Unidas was efficacious in increasing condom use during vaginal and anal
      sex during the past 90 days, reducing the number of days adolescents were under
      the influence of drugs or alcohol and had sex without a condom, reducing sexual
      partners, and preventing unprotected anal sex at the last sexual intercourse.
      Familias Unidas was also efficacious, relative to community practice, in
      increasing family functioning and most notably in increasing parent-adolescent
      communication and positive parenting. CONCLUSION: These results suggest that
      culturally tailored, family-centered prevention interventions may be appropriate
      and efficacious in reducing HIV risk behaviors among Hispanic delinquent
      adolescents. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01257022.

PMID- 21969364
TI  - Agrin binds to the N-terminal region of Lrp4 protein and stimulates association
      between Lrp4 and the first immunoglobulin-like domain in muscle-specific kinase
      (MuSK).
AB  - Neuromuscular synapse formation depends upon coordinated interactions between
      motor neurons and muscle fibers, leading to the formation of a highly specialized
      postsynaptic membrane and a highly differentiated nerve terminal. Synapse
      formation begins as motor axons approach muscles that are prepatterned in the
      prospective synaptic region in a manner that depends upon Lrp4, a member of the
      LDL receptor family, and muscle-specific kinase (MuSK), a receptor tyrosine
      kinase. Motor axons supply Agrin, which binds Lrp4 and stimulates further MuSK
      phosphorylation, stabilizing nascent synapses. How Agrin binds Lrp4 and
      stimulates MuSK kinase activity is poorly understood. Here, we demonstrate that
      Agrin binds to the N-terminal region of Lrp4, including a subset of the LDLa
      repeats and the first of four beta-propeller domains, which promotes association
      between Lrp4 and MuSK and stimulates MuSK kinase activity. In addition, we show
      that Agrin stimulates the formation of a functional complex between Lrp4 and MuSK
      on the surface of myotubes in the absence of the transmembrane and intracellular
      domains of Lrp4. Further, we demonstrate that the first Ig-like domain in MuSK,
      which shares homology with the NGF-binding region in Tropomyosin Receptor Kinase
      (TrKA), is required for MuSK to bind Lrp4. These findings suggest that Lrp4 is a
      cis-acting ligand for MuSK, whereas Agrin functions as an allosteric and
      paracrine regulator to promote association between Lrp4 and MuSK.

PMID- 21969366
TI  - Jumonji/ARID1 B (JARID1B) protein promotes breast tumor cell cycle progression
      through epigenetic repression of microRNA let-7e.
AB  - MicroRNAs (miRs) function as tumor suppressors or oncogenes in multiple tumor
      types. Although miR expression is tightly regulated, the molecular basis of miR
      regulation is poorly understood. Here, we investigated the influence of the
      histone demethylase Jumonji/ARID1 B (JARID1B) on miR regulation in breast tumor
      cells. In MCF-7 cells with stable RNAi-mediated suppression of JARID1B expression
      we identified altered regulation of multiple miRs including let-7e, a member of
      the let-7 family of tumor suppressor miRs. Chromatin immunoprecipitation analysis
      demonstrated JARID1B binding to the let-7e promoter region as well as removal of
      the of H3K4me3 histone mark associated with active gene expression. These results
      suggest that JARID1B epigenetically represses let-7e expression. JARID1B
      stimulates tumor cell proliferation by promoting the G(1) to S transition. As
      predicted, suppression of JARID1B resulted in an accumulation of MCF-7 cells in
      G(1). We confirmed that cyclin D1, which also promotes G(1) progression, is a
      direct target of let-7e, and we show that cyclin D1 expression is suppressed in
      JARID1B knockdown cells. Cyclin D1 expression and cell cycle progression were
      restored following inhibition of let-7e, suggesting that JARID1B repression of
      let-7e contributes to cyclin D1 expression and JARID1B-mediated cell cycle
      progression. Our results indicate that the JARID1B demethylase contributes to
      tumor cell proliferation through the epigenetic repression of a tumor suppressor
      miR.

PMID- 21969365
TI  - A mechanism underlying NOTCH-induced and ubiquitin-mediated JAK3 degradation.
AB  - Although NOTCH signaling is well known to regulate lymphopoiesis, Janus kinase 3
      (JAK3) also plays a critical role in promoting lymphocyte development. We have
      previously found that NOTCH signaling leads to the degradation of JAK3 in B
      lineage cells, suggesting that NOTCH signaling exerts its biological effect on
      lymphopoiesis through modulating JAK3 levels. Here, we delineate the biochemical
      mechanisms involved in NOTCH-induced JAK3 ubiquitination and degradation. NOTCH
      signaling is known to transcriptionally activate the genes encoding ASB2 (ankyrin
      repeat SOCS box containing protein 2) and SKP2 (S-phase kinase-associated protein
      2). We show that not only NOTCH but also ASB2 and SKP2 can promote the
      ubiquitination and degradation of JAK3. Both ASB2 and SKP2 can interact with JAK3
      through different domains; the FERM and pseudo-kinase domains each had high
      affinities for ASB2, whereas the kinase domain primarily associated with SKP2.
      ASB2 and SKP2 previously have been shown to associate with each other to bridge
      the formation of a non-canonical Cullin1 and Cullin5-containing dimeric E3 ligase
      complex. Interestingly, the R980W mutant of JAK3 exhibited diminished interaction
      with SKP2 and resistance to NOTCH or ASB2-induced degradation. Furthermore,
      dominant-negative mutants of either Cullin1 or Cullin5, which lack the C terminus
      responsible for recruiting the E2 enzymes, were able to prevent JAK3 degradation
      induced by both ASB2/SKP2 and NOTCH signaling. Together, these results suggest
      that JAK3 ubiquitination involves the non-canonical dimeric E3 ligase complex,
      and the R980W mutant will serve as an excellent tool for investigating the
      biological significance of NOTCH-mediated JAK3 turnover.

PMID- 21969367
TI  - Molecular characterization of the microRNA-138-Fos-like antigen 1 (FOSL1)
      regulatory module in squamous cell carcinoma.
AB  - MicroRNA-138 is one of the most frequently down-regulated microRNAs in cancer. We
      recently identified 51 candidate targets of microRNA-138 (Jiang, L., Dai, Y.,
      Liu, X., Wang, C., Wang, A., Chen, Z., Heidbreder, C. E., Kolokythas, A., and
      Zhou, X. (2011) Hum. Genet. 129, 189-197). Among these candidates, Fos-like
      antigen 1 (FOSL1) is a member of Fos gene family and is a known proto-oncogene.
      In this study, we first confirmed the microRNA-138-mediated down-regulation of
      FOSL1 in squamous cell carcinoma cell lines. We then demonstrated the effect of
      this microRNA-138-FOSL1 regulatory module on downstream genes (homolog of Snail 2
      (Snai2) expression and the Snai2-mediated repression of E-cadherin expression),
      as well as its contributions to tumorigenesis. The microRNA-138-directed
      recruitment of FOSL1 mRNA to the RNAi-induced silencing complex was confirmed by
      a ribonucleoprotein-immunoprecipitation assay. Three canonical and three high
      affinity non-canonical microRNA-138 (miR-138) targeting sites were identified on
      the FOSL1 mRNA: one in the 5'-UTR, three overlapping sites in the coding
      sequences, and two overlapping sites in the 3'-UTR. The direct targeting of miR
      138 to these sites was confirmed using luciferase reporter gene assays. In
      summary, we describe an important microRNA regulatory module, which may play an
      important role in cancer initiation and progression. Our results also provide
      evidence that microRNAs target both canonical and non-canonical targeting sites
      located in all areas of the mRNA molecule (e.g. 5'-UTR, coding sequences, and 3'
      UTR).

PMID- 21969368
TI  - Mechanistic studies of substrate-assisted inhibition of ubiquitin-activating
      enzyme by adenosine sulfamate analogues.
AB  - Ubiquitin-activating enzyme (UAE or E1) activates ubiquitin via an adenylate
      intermediate and catalyzes its transfer to a ubiquitin-conjugating enzyme (E2).
      MLN4924 is an adenosine sulfamate analogue that was identified as a selective,
      mechanism-based inhibitor of NEDD8-activating enzyme (NAE), another E1 enzyme, by
      forming a NEDD8-MLN4924 adduct that tightly binds at the active site of NAE, a
      novel mechanism termed substrate-assisted inhibition (Brownell, J. E., Sintchak,
      M. D., Gavin, J. M., Liao, H., Bruzzese, F. J., Bump, N. J., Soucy, T. A.,
      Milhollen, M. A., Yang, X., Burkhardt, A. L., Ma, J., Loke, H. K., Lingaraj, T.,
      Wu, D., Hamman, K. B., Spelman, J. J., Cullis, C. A., Langston, S. P., Vyskocil,
      S., Sells, T. B., Mallender, W. D., Visiers, I., Li, P., Claiborne, C. F., Rolfe,
      M., Bolen, J. B., and Dick, L. R. (2010) Mol. Cell 37, 102-111). In the present
      study, substrate-assisted inhibition of human UAE (Ube1) by another adenosine
      sulfamate analogue, 5'-O-sulfamoyl-N(6)-[(1S)-2,3-dihydro-1H-inden-1-yl]
      adenosine (Compound I), a nonselective E1 inhibitor, was characterized. Compound
      I inhibited UAE-dependent ATP-PP(i) exchange activity, caused loss of UAE
      thioester, and inhibited E1-E2 transthiolation in a dose-dependent manner.
      Mechanistic studies on Compound I and its purified ubiquitin adduct demonstrate
      that the proposed substrate-assisted inhibition via covalent adduct formation is
      entirely consistent with the three-step ubiquitin activation process and that the
      adduct is formed via nucleophilic attack of UAE thioester by the sulfamate group
      of Compound I after completion of step 2. Kinetic and affinity analysis of
      Compound I, MLN4924, and their purified ubiquitin adducts suggest that both the
      rate of adduct formation and the affinity between the adduct and E1 contribute to
      the overall potency. Because all E1s are thought to use a similar mechanism to
      activate their cognate ubiquitin-like proteins, the substrate-assisted inhibition
      by adenosine sulfamate analogues represents a promising strategy to develop
      potent and selective E1 inhibitors that can modulate diverse biological pathways.

PMID- 21969369
TI  - Sequence TTKF ? QE defines the site of proteolytic cleavage in Mhp683 protein, a
      novel glycosaminoglycan and cilium adhesin of Mycoplasma hyopneumoniae.
AB  - Mycoplasma hyopneumoniae colonizes the ciliated respiratory epithelium of swine,
      disrupting mucociliary function and inducing chronic inflammation. P97 and P102
      family members are major surface proteins of M. hyopneumoniae and play key roles
      in colonizing cilia via interactions with glycosaminoglycans and mucin. The p102
      paralog, mhp683, and homologs in strains from different geographic origins encode
      a 135-kDa pre-protein (P135) that is cleaved into three fragments identified here
      as P45(683), P48(683), and P50(683). A peptide sequence (TTKF?QE) was identified
      surrounding both cleavage sites in Mhp683. N-terminal sequences of P48(683) and
      P50(683), determined by Edman degradation and mass spectrometry, confirmed
      cleavage after the phenylalanine residue. A similar proteolytic cleavage site was
      identified by mass spectrometry in another paralog of the P97/P102 family.
      Trypsin digestion and surface biotinylation studies showed that P45(683),
      P48(683), and P50(683) reside on the M. hyopneumoniae cell surface. Binding
      assays of recombinant proteins F1(683)-F5(683), spanning Mhp683, showed saturable
      and dose-dependent binding to biotinylated heparin that was inhibited by
      unlabeled heparin, fucoidan, and mucin. F1(683)-F5(683) also bound porcine
      epithelial cilia, and antisera to F2(683) and F5(683) significantly inhibited
      cilium binding by M. hyopneumoniae cells. These data suggest that P45(683),
      P48(683), and P50(683) each display cilium- and proteoglycan-binding sites.
      Mhp683 is the first characterized glycosaminoglycan-binding member of the P102
      family.

PMID- 21969370
TI  - Histone chaperone FACT coordinates nucleosome interaction through multiple
      synergistic binding events.
AB  - In eukaryotic cells, DNA maintenance requires ordered disassembly and re-assembly
      of chromatin templates. These processes are highly regulated and require
      extrinsic factors such as chromatin remodelers and histone chaperones. The
      histone chaperone FACT (facilitates chromatin transcription) is a large
      heterodimeric complex with roles in transcription, replication, and repair. FACT
      promotes and subsequently restricts access to DNA as a result of dynamic
      nucleosome reorganization. However, until now, there lacked a truly quantitative
      assessment of the critical contacts mediating FACT function. Here, we demonstrate
      that FACT binds histones, DNA, and intact nucleosomes at nanomolar
      concentrations. We also determine roles for the histone tails in free histone and
      nucleosome binding by FACT. Furthermore, we propose that the conserved acidic C
      terminal domain of the FACT subunit Spt16 actively displaces nucleosomal DNA to
      provide access to the histone octamer. Experiments with tri-nucleosome arrays
      indicate a possible mode for FACT binding within chromatin. Together, the data
      reveal that specific FACT subunits synchronize interactions with various target
      sites on individual nucleosomes to generate a high affinity binding event and
      promote reorganization.

PMID- 21969372
TI  - Relative contribution of adipose triglyceride lipase and hormone-sensitive lipase
      to tumor necrosis factor-alpha (TNF-alpha)-induced lipolysis in adipocytes.
AB  - TNF-alpha potently stimulates basal lipolysis in adipocytes, which may contribute
      to hyperlipidemia and peripheral insulin resistance in obesity. Recent studies
      show that adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL)
      act sequentially in catalyzing the first two steps of adipose lipolysis in
      response to beta-adrenergic stimulation. Here, we sought to determine their
      functional roles in TNF-alpha-induced lipolysis. Silencing of ATGL expression in
      adipocytes almost completely abolished basal and TNF-alpha-induced glycerol
      release. In comparison, the glycerol release under the same conditions was only
      partially decreased upon reduction in expression of either HSL or the ATGL
      coactivator CGI-58. Interestingly, overexpression of ATGL restored the lipolytic
      rates in cells with silenced HSL or CGI-58, indicating a predominant role for
      ATGL. While expression of ATGL, HSL and CGI-58 remains mostly unaffected, TNF
      alpha treatment caused a rapid abrogation of the ATGL inhibitory protein G0S2.
      TNF-alpha drastically decreased the level of G0S2 mRNA, and the level of G0S2
      protein could be maintained by inhibiting proteasomal protein degradation using
      MG-132. Furthermore, coexpression of G0S2 was able to significantly decrease TNF
      alpha-stimulated lipolysis mediated by overexpressed ATGL or CGI-58. We propose
      that the early reduction in G0S2 content is permissive for TNF-alpha-induced
      lipolysis.

PMID- 21969371
TI  - Inhibition or ablation of p21-activated kinase (PAK1) disrupts glucose
      homeostatic mechanisms in vivo.
AB  - The p21-activated kinase PAK1 is implicated in tumorigenesis, and efforts to
      inhibit PAK1 signaling as a means to induce tumor cell apoptosis are underway.
      However, PAK1 has also been implicated as a positive effector of mechanisms in
      clonal pancreatic beta cells and skeletal myotubes that would be crucial to
      maintaining glucose homeostasis in vivo. Of relevance, human islets of Type 2
      diabetic donors contained ~80% less PAK1 protein compared with non-diabetics,
      implicating PAK1 in islet signaling/scaffolding functions. Mimicking this, islets
      from PAK1(-/-) knock-out mice exhibited profound defects in the second/sustained
      phase of insulin secretion. Reiteration of this specific defect by human islets
      treated with the PAK1 signaling inhibitor IPA3 revealed PAK1 signaling to be of
      primary functional importance. Analyses of human and mouse islet beta cell
      signaling revealed PAK1 activation to be 1) dependent upon Cdc42 abundance, 2)
      crucial for signaling downstream to activate ERK1/2, but 3) dispensable for
      cofilin phosphorylation. Importantly, the PAK1(-/-) knock-out mice were found to
      exhibit whole body glucose intolerance in vivo. Exacerbating this, the PAK1(-/-)
      knock-out mice also exhibited peripheral insulin resistance. Insulin resistance
      was coupled to ablation of insulin-stimulated GLUT4 translocation in skeletal
      muscle from PAK1(-/-) knock-out mice, and in sharp contrast to islet beta cells,
      skeletal muscle PAK1 loss was underscored by defective cofilin phosphorylation
      but normal ERK1/2 activation. Taken together, these data provide the first human
      islet and mammalian in vivo data unveiling the key and crucial roles for
      differential PAK1 signaling in the multi-tissue regulation of whole body glucose
      homeostasis.

PMID- 21969373
TI  - Ordered assembly of heat shock proteins, Hsp26, Hsp70, Hsp90, and Hsp104, on
      expanded polyglutamine fragments revealed by chemical probes.
AB  - In Saccharomyces cerevisae, expanded polyglutamine (polyQ) fragments are
      assembled into discrete cytosolic aggregates in a process regulated by the
      molecular chaperones Hsp26, Hsp70, Hsp90, and Hsp104. To better understand how
      the different chaperones might cooperate during polyQ aggregation, we used
      sequential immunoprecipitations and mass spectrometry to identify proteins
      associated with either soluble (Q25) or aggregation-prone (Q103) fragments at
      both early and later times after induction of their expression. We found that
      Hsp26, Hsp70, Hsp90, and other chaperones interact with Q103, but not Q25, within
      the first 2 h. Further, Hsp70 and Hsp90 appear to be partially released from Q103
      prior to the maturation of the aggregates and before the recruitment of Hsp104.
      To test the importance of this seemingly ordered process, we used a chemical
      probe to artificially enhance Hsp70 binding to Q103. This treatment retained both
      Hsp70 and Hsp90 on the polyQ fragment and, interestingly, limited subsequent
      exchange for Hsp26 and Hsp104, resulting in incomplete aggregation. Together,
      these results suggest that partial release of Hsp70 may be an essential step in
      the continued processing of expanded polyQ fragments in yeast.

PMID- 21969374
TI  - Calcium-sensing receptor modulates cell adhesion and migration via integrins.
AB  - The calcium-sensing receptor (CaSR) is a family C G protein-coupled receptor that
      is activated by elevated levels of extracellular divalent cations. The CaSR
      couples to members of the G(q) family of G proteins, and in the endocrine system
      this receptor is instrumental in regulating the release of parathyroid hormone
      from the parathyroid gland and calcitonin from thyroid cells. Here, we
      demonstrate that in medullary thyroid carcinoma cells, the CaSR promotes cellular
      adhesion and migration via coupling to members of the integrin family of
      extracellular matrix-binding proteins. Immunopurification and mass spectrometry,
      co-immunoprecipitation, and co-localization studies showed that the CaSR and
      beta1-containing integrins are components of a macromolecular protein complex. In
      fibronectin-based cell adhesion and migration assays, the CaSR-positive
      allosteric modulator NPS R-568 induced a concentration-dependent increase in cell
      adhesion and migration; both of these effects were blocked by a specific CaSR
      negative allosteric modulator. These effects were mediated by integrins because
      they were blocked by a peptide inhibitor of integrin binding to fibronectin and
      beta1 knockdown experiments. An analysis of intracellular signaling pathways
      revealed a key role for CaSR-induced phospholipase C activation and the release
      of intracellular calcium. These results demonstrate for the first time that an
      ion-sensing G protein-coupled receptor functionally couples to the integrins and,
      in conjunction with intracellular calcium release, promotes cellular adhesion and
      migration in tumor cells. The significance of this interaction is further
      highlighted by studies implicating the CaSR in cancer metastasis, axonal growth,
      and stem cell attachment, functions that rely on integrin-mediated cell adhesion.

PMID- 21969375
TI  - beta-hairpin peptide that targets vascular endothelial growth factor (VEGF)
      receptors: design, NMR characterization, and biological activity.
AB  - VEGF receptors have been the target of intense research aimed to develop
      molecules able to inhibit or stimulate angiogenesis. Based on the x-ray structure
      of the complex placental growth factor-VEGF receptor 1(D2), we designed a VEGF
      receptor-binding peptide reproducing the placental growth factor beta-hairpin
      region Gln(87)-Val(100) that is involved in receptor recognition. A
      conformational analysis showed that the designed peptide adopts the expected fold
      in pure water. Moreover, a combination of NMR interaction analysis and cell
      binding studies were used to demonstrate that the peptide targets VEGF receptors.
      The VEGF receptor 1(D2)-interacting residues were characterized at the molecular
      level, and they correspond to the residues recognizing the placental growth
      factor sequence Gln(87)-Val(100). Finally, the peptide biological activity was
      characterized in vitro and in vivo, and it showed a VEGF-like behavior. Indeed,
      the peptide activated VEGF-dependent intracellular pathways, induced endothelial
      cell proliferation and rescue from apoptosis, and promoted angiogenesis in vivo.
      This compound is one of the few peptides known with proangiogenic activity, which
      makes it a candidate for the development of a novel peptide-based drug for
      medical applications in therapeutic angiogenesis.

PMID- 21969376
TI  - Brain-derived neurotrophic factor (BDNF) enhances GABA transport by modulating
      the trafficking of GABA transporter-1 (GAT-1) from the plasma membrane of rat
      cortical astrocytes.
AB  - The gamma-aminobutyric acid (GABA) transporters (GATs) are located in the plasma
      membrane of neurons and astrocytes and are responsible for termination of
      GABAergic transmission. It has previously been shown that brain derived
      neurotrophic factor (BDNF) modulates GAT-1-mediated GABA transport in nerve
      terminals and neuronal cultures. We now report that BDNF enhances GAT-1-mediated
      GABA transport in cultured astrocytes, an effect mostly due to an increase in the
      V(max) kinetic constant. This action involves the truncated form of the TrkB
      receptor (TrkB-t) coupled to a non-classic PLC-gamma/PKC-delta and ERK/MAPK
      pathway and requires active adenosine A(2A) receptors. Transport through GAT-3 is
      not affected by BDNF. To elucidate if BDNF affects trafficking of GAT-1 in
      astrocytes, we generated and infected astrocytes with a functional mutant of the
      rat GAT-1 (rGAT-1) in which the hemagglutinin (HA) epitope was incorporated into
      the second extracellular loop. An increase in plasma membrane of HA-rGAT-1 as
      well as of rGAT-1 was observed when both HA-GAT-1-transduced astrocytes and rGAT
      1-overexpressing astrocytes were treated with BDNF. The effect of BDNF results
      from inhibition of dynamin/clathrin-dependent constitutive internalization of GAT
      1 rather than from facilitation of the monensin-sensitive recycling of GAT-1
      molecules back to the plasma membrane. We therefore conclude that BDNF enhances
      the time span of GAT-1 molecules at the plasma membrane of astrocytes. BDNF may
      thus play an active role in the clearance of GABA from synaptic and extrasynaptic
      sites and in this way influence neuronal excitability.

PMID- 21969377
TI  - Overexpression of the c-myc oncogene inhibits nonsense-mediated RNA decay in B
      lymphocytes.
AB  - The Myc transcription factor plays a vital role in both normal cellular
      physiology and in many human cancers. We have recently demonstrated that nonsense
      mediated RNA decay (NMD), a mechanism that rapidly degrades select mRNAs, is
      inhibited by the stress-induced phosphorylation of translation initiation factor
      eIF2alpha, and this inhibition stabilizes many transcripts necessary for
      tumorigenesis. Here, we demonstrate that NMD is inhibited by high Myc expression.
      We show that the phosphorylation of eIF2alpha, likely due to the ability of Myc
      to generate reactive oxygen species and augment endoplasmic reticulum stress, is
      necessary for the inhibition of NMD by Myc. The inhibition of NMD both stabilizes
      and up-regulates multiple Myc targets, suggesting that the inhibition of NMD may
      play an important role in the dynamic regulation of genes by Myc.

PMID- 21969378
TI  - Alternative splicing produces Nanog protein variants with different capacities
      for self-renewal and pluripotency in embryonic stem cells.
AB  - Embryonic stem (ES) cells are distinguished by their ability to undergo unlimited
      self-renewal although retaining pluripotency, the capacity to specify cells of
      all germ layers. Alternative splicing contributes to these biological processes
      by vastly increasing the protein coding repertoire, enabling genes to code for
      novel variants that may confer different biological functions. The homeodomain
      transcription factor Nanog acts collaboratively with core factors Oct4 and Sox2
      to govern the maintenance of pluripotency. We have discovered that Nanog is
      regulated by alternative splicing. Two novel exons and six subexons have been
      identified that extend the known Nanog gene structure and protein coding
      capacity. Alternative splicing results in two novel Nanog protein variants with
      attenuated capacities for self-renewal and pluripotency in ES cells. Our previous
      results have implicated the C-terminal domain, including the tryptophan-rich (WR)
      domain of Nanog, to be important for the function of Nanog (Wang, J., Levasseur,
      D. N., and Orkin, S. H. (2008) Proc. Natl. Acad. Sci. U.S.A. 105, 6326-6331).
      Using point mutation analyses, serine 2 (Ser-2) of Nanog has been identified as
      critical for ES cell self-renewal and for stabilizing a pluripotent gene
      signature. An inducible conditional knock-out was created to test the ability of
      new Nanog variants to genetically complement Nanog null ES cells. These results
      reveal for the first time an expanded Nanog protein coding capacity. We further
      reveal that a short region of the N-terminal domain and a single phosphorylatable
      Ser-2 is essential for the maintenance of self-renewal and pluripotency,
      demonstrating that this region of the protein is highly regulated.

PMID- 21969379
TI  - MicroRNA-processing enzyme Dicer is required in epicardium for coronary
      vasculature development.
AB  - The epicardium is a sheet of epithelial cells covering the heart during early
      cardiac development. In recent years, the epicardium has been identified as an
      important contributor to cardiovascular development, and epicardium-derived cells
      have the potential to differentiate into multiple cardiac cell lineages. Some
      epicardium-derived cells that undergo epithelial-to-mesenchymal transition and
      delaminate from the surface of the developing heart subsequently invade the
      myocardium and differentiate into vascular smooth muscle of the developing
      coronary vasculature. MicroRNAs (miRNAs) have been implicated broadly in tissue
      patterning and development, including in the heart, but a role in epicardium is
      unknown. To examine the role of miRNAs during epicardial development, we
      conditionally deleted the miRNA-processing enzyme Dicer in the proepicardium
      using Gata5-Cre mice. Epicardial Dicer mutant mice are born in expected Mendelian
      ratios but die immediately after birth with profound cardiac defects, including
      impaired coronary vessel development. We found that loss of Dicer leads to
      impaired epicardial epithelial-to-mesenchymal transition and a reduction in
      epicardial cell proliferation and differentiation into coronary smooth muscle
      cells. These results demonstrate a critical role for Dicer, and by implication
      miRNAs, in murine epicardial development.

PMID- 21969380
TI  - Disordered binding of small molecules to Abeta(12-28).
AB  - In recent years, an increasing number of small molecules and short peptides have
      been identified that interfere with aggregation and/or oligomerization of the
      Alzheimer beta-amyloid peptide (Abeta). Many of them possess aromatic moieties,
      suggesting a dominant role for those in interacting with Abeta along various
      stages of the aggregation process. In this study, we attempt to elucidate whether
      interactions of such aromatic inhibitors with monomeric Abeta(12-28) point to a
      common mechanism of action by performing atomistic molecular dynamics simulations
      at equilibrium. Our results suggest that, independently of the presence of
      inhibitors, monomeric Abeta(12-28) populates a partially collapsed ensemble that
      is largely devoid of canonical secondary structure at 300 K and neutral pH. The
      small molecules have different affinities for Abeta(12-28) that can be partially
      rationalized by the balance of aromatic and charged moieties constituting the
      molecules. There are no predominant binding modes, although aggregation
      inhibitors preferentially interact with the N-terminal portion of the fragment
      (residues 13-20). Analysis of the free energy landscape of Abeta(12-28) reveals
      differences highlighted by altered populations of a looplike conformer in the
      presence of inhibitors. We conclude that intrinsic disorder of Abeta persists at
      the level of binding small molecules and that inhibitors can significantly alter
      properties of monomeric Abeta via multiple routes of differing specificity.

PMID- 21969381
TI  - Direct interaction of mitochondrial targeting presequences with purified
      components of the TIM23 protein complex.
AB  - Precursor proteins that are imported from the cytosol into the matrix of
      mitochondria carry positively charged amphipathic presequences and cross the
      inner membrane with the help of vital components of the TIM23 complex. It is
      currently unclear which subunits of the TIM23 complex recognize and directly bind
      to presequences. Here we analyzed the binding of presequence peptides to purified
      components of the TIM23 complex. The interaction of three different presequences
      with purified soluble domains of yeast Tim50 (Tim50IMS), Tim23 (Tim23IMS), and
      full-length Tim44 was examined. Using chemical cross-linking and surface plasmon
      resonance we demonstrate, for the first time, the ability of purified Tim50IMS
      and Tim44 to interact directly with the yeast Hsp60 presequence. We also analyzed
      their interaction with presequences derived from precursors of yeast
      mitochondrial 70-kDa heat shock protein (mHsp70) and of bovine cytochrome
      P450SCC. Moreover, we characterized the nature of the interactions and determined
      their KDs. On the basis of our results, we suggest a mechanism of translocation
      where stronger interactions of the presequences on the trans side of the channel
      support the import of precursor proteins through TIM23 into the matrix.

PMID- 21969383
TI  - Evaluation of human papilloma virus diagnostic testing in oropharyngeal squamous
      cell carcinoma: sensitivity, specificity, and prognostic discrimination.
AB  - PURPOSE: Human papillomavirus-16 (HPV16) is the causative agent in a biologically
      distinct subset of oropharyngeal squamous cell carcinoma (OPSCC) with highly
      favorable prognosis. In clinical trials, HPV16 status is an essential inclusion
      or stratification parameter, highlighting the importance of accurate testing.
      EXPERIMENTAL DESIGN: Fixed and fresh-frozen tissue from 108 OPSCC cases were
      subject to eight possible assay/assay combinations: p16 immunohistochemistry (p16
      IHC); in situ hybridization for high-risk HPV (HR HPV ISH); quantitative PCR
      (qPCR) for both viral E6 RNA (RNA qPCR) and DNA (DNA qPCR); and combinations of
      the above. RESULTS: HPV16-positive OPSCC presented in younger patients (mean 7.5
      years younger, P = 0.003) who smoked less than HPV-negative patients (P = 0.007).
      The proportion of HPV16-positive cases increased from 15% to 57% (P = 0.001)
      between 1988 and 2009. A combination of p16 IHC/DNA qPCR showed acceptable
      sensitivity (97%) and specificity (94%) compared with the RNA qPCR "gold
      standard", as well as being the best discriminator of favorable outcome (overall
      survival P = 0.002). p16 IHC/HR HPV ISH also had acceptable specificity (90%) but
      the substantial reduction in its sensitivity (88%) impacted upon its prognostic
      value (P = 0.02). p16 IHC, HR HPV ISH, or DNA qPCR was not sufficiently specific
      to recommend in clinical trials when used in isolation. CONCLUSIONS: Caution must
      be exercised in applying HPV16 diagnostic tests because of significant
      disparities in accuracy and prognostic value in previously published techniques.

PMID- 21969384
TI  - OsYSL6 is involved in the detoxification of excess manganese in rice.
AB  - Yellow Stripe-Like (YSL) proteins belong to the oligopeptide transporter family
      and have been implicated in metal transport and homeostasis in different plant
      species. Here, we functionally characterized a rice (Oryza sativa) YSL member,
      OsYSL6. Knockout of OsYSL6 resulted in decreased growth of both roots and shoots
      only in the high-manganese (Mn) condition. There was no difference in the
      concentration of total Mn and other essential metals between the wild-type rice
      and the knockout line, but the knockout line showed a higher Mn concentration in
      the leaf apoplastic solution and a lower Mn concentration in the symplastic
      solution than wild-type rice. OsYSL6 was constitutively expressed in both the
      shoots and roots, and the expression level was not affected by either deficiency
      or toxicity of various metals. Furthermore, the expression level increased with
      leaf age. Analysis with OsYSL6 promoter-green fluorescent protein transgenic rice
      revealed that OsYSL6 was expressed in all cells of both the roots and shoots.
      Heterogolous expression of OsYSL6 in yeast showed transport activity for the Mn
      nicotianamine complex but not for the Mn-mugineic acid complex. Taken together,
      our results suggest that OsYSL6 is a Mn-nicotianamine transporter that is
      required for the detoxification of excess Mn in rice.

PMID- 21969387
TI  - How well are we training the next generation of clinical pathologists and
      clinical laboratory directors? A global perspective.

PMID- 21969388
TI  - Amigos.

PMID- 21969385
TI  - The Arabidopsis RING E3 ubiquitin ligase AtAIRP2 plays combinatory roles with
      AtAIRP1 in abscisic acid-mediated drought stress responses.
AB  - The ubiquitin (Ub)-26S proteasome pathway is implicated in various cellular
      processes in higher plants. AtAIRP1, a C3H2C3-type RING (for Really Interesting
      New Gene) E3 Ub ligase, is a positive regulator in the Arabidopsis (Arabidopsis
      thaliana) abscisic acid (ABA)-dependent drought response. Here, the AtAIRP2 (for
      Arabidopsis ABA-insensitive RING protein 2) gene was identified and
      characterized. AtAIRP2 encodes a cytosolic C3HC4-type RING E3 Ub ligase whose
      expression was markedly induced by ABA and dehydration stress. Thus, AtAIRP2
      belongs to a different RING subclass than AtAIRP1 with a limited sequence
      identity. AtAIRP2-overexpressing transgenic (35S:AtAIRP2-sGFP) and atairp2 loss
      of-function mutant plants exhibited hypersensitive and hyposensitive phenotypes,
      respectively, to ABA in terms of seed germination, root growth, and stomatal
      movement. 35S:AtAIRP2-sGFP plants were highly tolerant to severe drought stress,
      and atairp2 alleles were more susceptible to water stress than were wild-type
      plants. Higher levels of drought-induced hydrogen peroxide production were
      detected in 35S:AtAIRP2-sGFP as compared with atairp2 plants. ABA-inducible
      drought-related genes were up-regulated in 35S:AtAIRP2-sGFP and down-regulated in
      atairp2 progeny. The positive effects of AtAIRP2 on ABA-induced stress genes were
      dependent on SNF1-related protein kinases, key components of the ABA signaling
      pathway. Therefore, AtAIRP2 is involved in positive regulation of ABA-dependent
      drought stress responses. To address the functional relationship between AtAIRP1
      and AtAIRP2, FLAG-AtAIRP1 and AtAIRP2-sGFP genes were ectopically expressed in
      atairp2-2 and atairp1 plants, respectively. Constitutive expression of FLAG
      AtAIRP1 and AtAIRP2-sGFP in atairp2-2 and atairp1 plants, respectively,
      reciprocally rescued the loss-of-function ABA-insensitive phenotypes during
      germination. Additionally, atairp1/35S:AtAIRP2-sGFP and atairp2-2/35S:FLAG
      AtAIRP1 complementation lines were more tolerant to dehydration stress relative
      to atairp1 and atairp2-2 single knockout plants. Overall, these results suggest
      that AtAIRP2 plays combinatory roles with AtAIRP1 in Arabidopsis ABA-mediated
      drought stress responses.

PMID- 21969389
TI  - The 1990s: a decade of change in understanding children with ongoing conditions.

PMID- 21969386
TI  - Missense mutation in the amino terminus of phytochrome A disrupts the nuclear
      import of the photoreceptor.
AB  - Phytochromes are the red/far-red photoreceptors in higher plants. Among them,
      phytochrome A (PHYA) is responsible for the far-red high-irradiance response and
      for the perception of very low amounts of light, initiating the very-low-fluence
      response. Here, we report a detailed physiological and molecular characterization
      of the phyA-5 mutant of Arabidopsis (Arabidopsis thaliana), which displays
      hyposensitivity to continuous low-intensity far-red light and shows reduced very
      low-fluence response and high-irradiance response. Red light-induced degradation
      of the mutant phyA-5 protein appears to be normal, yet higher residual amounts of
      phyA-5 are detected in seedlings grown under low-intensity far-red light. We show
      that (1) the phyA-5 mutant harbors a new missense mutation in the PHYA amino
      terminal extension domain and that (2) the complex phenotype of the mutant is
      caused by reduced nuclear import of phyA-5 under low fluences of far-red light.
      We also demonstrate that impaired nuclear import of phyA-5 is brought about by
      weakened binding affinity of the mutant photoreceptor to nuclear import
      facilitators FHY1 (for FAR-RED ELONGATED HYPOCOTYL1) and FHL (for FHY1-LIKE).
      Finally, we provide evidence that the signaling and degradation kinetics of
      constitutively nuclear-localized phyA-5 and phyA are identical. Taken together,
      our data show that aberrant nucleo/cytoplasmic distribution impairs light-induced
      degradation of this photoreceptor and that the amino-terminal extension domain
      mediates the formation of the FHY1/FHL/PHYA far-red-absorbing form complex,
      whereby it plays a role in regulating the nuclear import of phyA.

PMID- 21969390
TI  - Incidence and age-specific presentation of restrictive eating disorders in
      children: a Canadian Paediatric Surveillance Program study.
AB  - OBJECTIVES: To document and describe the incidence and age-specific presentation
      of early-onset restrictive eating disorders in children across Canada. DESIGN:
      Surveillance study. Cases were ascertained through the Canadian Paediatric
      Surveillance Program by surveying approximately 2453 Canadian pediatricians (a
      95% participation rate) monthly during a 2-year period. SETTING: Canadian
      pediatric practices. PARTICIPANTS: Pediatricians and pediatric subspecialists.
      MAIN OUTCOME MEASURES: A description of clinical presentations and
      characteristics of eating disorders in this population and the incidence of
      restrictive eating disorders in children. RESULTS: The incidence of early-onset
      restrictive eating disorders in children aged 5 to 12 years seen by pediatricians
      was 2.6 cases per 100 000 person-years. The ratio of girls to boys was 6:1, and
      47.1% of girls and 54.5% of boys showed signs of growth delay. Forty-six percent
      of children were below the 10th percentile for body mass index, 34.2% were
      initially seen with unstable vital signs, and 47.2% required hospital admission.
      Only 62.1% of children met criteria for anorexia nervosa. Although children with
      anorexia nervosa were more likely to be medically compromised, some children who
      did not meet criteria for anorexia nervosa were equally medically unstable.
      CONCLUSIONS: Young children are seen with clinically significant restrictive
      eating disorders, with the incidence exceeding that of type 2 diabetes mellitus.
      These eating disturbances can result in serious medical consequences, ranging
      from growth delay to unstable vital signs, which can occur in the absence of
      weight loss or other restrictive eating disorder symptoms.

PMID- 21969391
TI  - The intergenerational transmission of thinness.
AB  - OBJECTIVES: To examine intergenerational associations for thinness and to compare
      maternal and paternal effects. DESIGN: Population-based, cross-sectional design
      using data from the Health Survey for England from January 1, 2001, through
      December 31, 2006. SETTING: The Health Survey for England, an annual, national
      survey representative of the population living in private households in England.
      PARTICIPANTS: Families with children and adolescents aged 2 to 15 years with
      anthropometric data available for children and adolescents and 2 parents (N =
      4423 families, N = 7078 children and adolescents). MAIN EXPOSURE: Trained
      interviewers collected height and weight measurements. MAIN OUTCOME MEASURE:
      Child/adolescent thinness, categorized using International Obesity Task Force
      criteria. RESULTS: Of 7078 children and adolescents, 402 (5.7%) were categorized
      as being thin. Thinness was more common in 2- to 5-year-olds (odds ratio, 1.61;
      95% confidence interval, 1.22-2.13) than in 11- to 15-year-olds and in children
      and adolescents from ethnic minority (black: 2.28; 1.22-4.26; and Asian: 3.65;
      2.76-4.83) than white backgrounds, but no differences were observed by sex or
      socioeconomic status. The strongest predictor of child/adolescent thinness was
      parental weight status. The prevalence of thinness was highest (16.2%) when both
      parents were thinner and progressively lower when both parents were in the upper
      half of the healthy-weight range (7.8%) or were overweight (5.3%) or obese
      (2.5%), with no differences in the magnitude of maternal and paternal influences.
      CONCLUSIONS: These results are consistent with the idea that many cases of
      thinness are likely to represent the low end of the healthy distribution of
      weight and, as such, are likely to have a primarily genetic origin.

PMID- 21969392
TI  - Developmental trajectories of body mass index in early childhood and their risk
      factors: an 8-year longitudinal study.
AB  - OBJECTIVES: To identify groups of children with distinct developmental
      trajectories of body mass index (BMI), calculated as weight in kilograms divided
      by height in meters squared, between the ages of 5 months and 8 years and
      identify early-life risk factors that distinguish children in an atypically
      elevated BMI trajectory group. DESIGN: Prospective cohort study. SETTING:
      Families with a child born between October 1997 and July 1998 in the province of
      Quebec, Canada. PARTICIPANTS: A representative sample of children (N = 2120)
      selected through birth registries for the Quebec Longitudinal Study of Child
      Development. Children for whom BMI data were available for at least 5 time points
      were retained in the present study (n = 1957). MAIN EXPOSURES: Early-life factors
      putatively associated with BMI, assessed by maternal report. OUTCOME MEASURE:
      Group-based trajectories of children's BMI, identified with a semiparametric
      modeling method from raw BMI values at each age. RESULTS: Three trajectories of
      BMI were identified: low-stable (54.5% of children), moderate (41.0%), and high
      rising (4.5%). The high-rising group was characterized by an increasing average
      BMI, which exceeded international cutoff values for obesity by age 8 years. Two
      maternal risk factors were associated with the high-rising group as compared with
      the low-stable and moderate groups combined: maternal BMI (odds ratio, 2.38; 95%
      confidence interval, 1.38-4.54 for maternal overweight and 6.33; 3.82-11.85 for
      maternal obesity) and maternal smoking during pregnancy (2.28; 1.49-4.04).
      CONCLUSIONS: Children continuing on an elevated BMI trajectory leading to obesity
      in middle childhood can be distinguished from children on a normative BMI
      trajectory as early as age 3.5 years. Important and preventable risk factors for
      childhood obesity are in place before birth.

PMID- 21969393
TI  - Retinal hemorrhages in low-risk children evaluated for physical abuse.
AB  - OBJECTIVES: To describe the prevalence of retinal hemorrhage (RH) in children
      without intracranial injury who are being evaluated for abusive head trauma and
      to validate previously derived criteria for identifying patients within this
      population who are at low risk of having RH on dilated eye examination. DESIGN:
      Medical record review. SETTING: Children's Hospital of Pittsburgh of University
      of Pittsburgh Medical Center from January 1, 2006, to April 30, 2010.
      PARTICIPANTS: One hundred ninety-four infants and children evaluated for physical
      abuse by the hospital Child Protection Team who did not have intracranial injury
      and who underwent a dilated eye examination to evaluate for RH. MAIN OUTCOME
      MEASURE: Number of children with RH who met a set of low-risk criteria: no
      intracranial hemorrhage with or without a simple, nonoccipital skull fracture,
      normal mental status, and no bruising on the head or face. RESULTS: Of the 194
      patients without intracranial injury who underwent dilated eye examination, 141
      children (72.7%) met low-risk criteria. None of these 141 patients had RH. Of the
      53 participants who did not meet low-risk criteria, 2 children (3.8%) had RH.
      CONCLUSIONS: In children evaluated for physical abuse who fulfill a set of low
      risk criteria, the dilated eye examination should not be a necessary component of
      the abuse evaluation. Use of these criteria can significantly decrease the number
      of children who need to undergo a dilated eye examination as part of an
      evaluation for abusive head trauma.

PMID- 21969394
TI  - Judicial outcomes of child abuse homicide.
AB  - OBJECTIVES: To determine whether convictions and sentencing differ between child
      abuse homicide cases and adult homicide cases and to identify characteristics of
      the victim, suspect, or crime that influence conviction and sentencing results.
      DESIGN: Retrospective case review. SETTING: Homicide data abstracted from the
      National Violent Death Reporting System in Utah. PARTICIPANTS: All deaths
      classified as homicide in Utah between January 1, 2002, and December 31, 2007.
      MAIN EXPOSURE: Judicial processing of homicide cases for conviction and
      sentencing results. MAIN OUTCOME MEASURES: Conviction rate, level of felony
      conviction, and severity of sentencing for suspects of child abuse homicide vs
      adult homicide. RESULTS: Utah had 373 homicide victims during the study period;
      52 cases were child abuse homicide. Among 211 homicide cases with an identified
      suspect, conviction rates for child abuse homicide (88.2%) and adult homicide
      (83.0%) were similar (risk ratio, 1.0; 95% confidence interval [CI], 0.8-1.4).
      There were no significant differences in level of felony conviction (adjusted
      risk ratio, 0.8; 95% CI, 0.4-1.3) or severity of sentencing (adjusted risk ratio,
      0.8; 95% CI, 0.5-1.5) for suspects of child abuse homicide vs adult homicide.
      Among child abuse homicide cases, no demographic factor was significantly
      associated with felony conviction results. CONCLUSION: Suspects of child abuse
      homicide are convicted at a rate similar to that of suspects of adult homicide
      and receive similar levels of felony conviction and severity of sentencing.

PMID- 21969396
TI  - Occult serious bacterial infection in infants younger than 60 to 90 days with
      bronchiolitis: a systematic review.
AB  - OBJECTIVE: To summarize the risk of occult serious bacterial infection in the
      youngest febrile infants presenting with either clinical bronchiolitis or
      respiratory syncytial virus infection. DATA SOURCES: We performed a systematic
      search of the Medline database for studies reporting rates of serious bacterial
      infection in infants younger than 90 days with clinical bronchiolitis and/or
      respiratory syncytial virus infection. STUDY SELECTION: Studies reporting on
      cultures performed at the time of presentation to care and providing a
      denominator, ie, total number of each type of culture obtained, were analyzed.
      MAIN EXPOSURE: Admission for bronchiolitis. MAIN OUTCOME MEASURES: Age-specific
      rates of urinary tract infection, bacteremia, and meningitis were extracted.
      RESULTS: The weighted rate of urinary tract infections in the youngest infants in
      the 11 studies analyzed was 3.3% (95% confidence interval, 1.9%-5.7%). No case of
      bacteremia was reported in 8 of 11 studies. No case of meningitis was reported in
      any of the studies. Summary statistics for meningitis and bacteremia are not
      provided because of an excess of zero events in these samples. CONCLUSIONS: A
      screening approach to culturing for serious bacterial infections in febrile
      infants presenting with bronchiolitis or respiratory syncytial virus infection is
      very low yield. The rate of urine cultures positive for bacteria remains
      significant, though asymptomatic bacteriuria may confound these results.

PMID- 21969395
TI  - Health status of extremely low-birth-weight children at 8 years of age: child and
      parent perspective.
AB  - OBJECTIVES: To compare the self-reported health of extremely low-birth-weight
      (ELBW; <1 kg) preterm children with that of normal-birth-weight (NBW) control
      children and the children's perspective with that of their parents. DESIGN: We
      administered questionnaires to the ELBW and NBW children and their parents from
      March 1, 2000, through February 2003. SETTING: A children's hospital.
      PARTICIPANTS: Two hundred two ELBW children and 176 NBW children aged 8 years of
      similar sociodemographic status. MAIN EXPOSURE: Birth weight of less than 1 kg.
      MAIN OUTCOME MEASURES: The Child Health and Illness Profile-Child Edition child
      and parent reports. RESULTS: There was poor agreement between the parent and
      child ratings of health for the ELBW and NBW cohorts. The ELBW children rated
      their health as similar to that of NBW children. In contrast, parents of ELBW
      children reported significantly poorer health for their children than parents of
      NBW controls, including poorer satisfaction with health, comfort, and achievement
      and less risk avoidance. CONCLUSIONS: There is poor agreement between child and
      parent reports of health. At 8 years of age, ELBW children rate their health as
      similar to that of NBW controls. Their parents, however, report significantly
      poorer health. Both perspectives need to be considered when making health care
      decisions.

PMID- 21969397
TI  - Picture of the month. Recurrent biliary colic in a young girl.

PMID- 21969398
TI  - A recurring question: are there health effects of power-frequency magnetic
      fields?

PMID- 21969399
TI  - Advice for patients. School bullying.

PMID- 21969400
TI  - Cardiovascular.

PMID- 21969401
TI  - Neurosciences.

PMID- 21969403
TI  - Reaching outside of our community.

PMID- 21969405
TI  - Mandatory vaccinations: The Canadian picture.

PMID- 21969404
TI  - Impaired branched chain amino acid metabolism alters feeding behavior and
      increases orexigenic neuropeptide expression in the hypothalamus.
AB  - Elevation of dietary or brain leucine appears to suppress food intake via a
      mechanism involving mechanistic target of rapamycin, AMPK, and/or branched chain
      amino acid (BCAA) metabolism. Mice bearing a deletion of mitochondrial branched
      chain aminotransferase (BCATm), which is expressed in peripheral tissues (muscle)
      and brain glia, exhibit marked increases in circulating BCAAs. Here, we test
      whether this increase alters feeding behavior and brain neuropeptide expression.
      Circulating and brain levels of BCAAs were increased two- to four-fold in BCATm
      deficient mice (KO). KO mice weighed less than controls (25.9 vs 20.4 g, P<0.01),
      but absolute food intake was relatively unchanged. In contrast to wild-type mice,
      KO mice preferred a low-BCAA diet to a control diet (P<0.05) but exhibited no
      change in preference for low- vs high-protein (HP) diets. KO mice also exhibited
      low leptin levels and increased hypothalamic Npy and Agrp mRNA. Normalization of
      circulating leptin levels had no effect on either food preference or the
      increased Npy and Agrp mRNA expression. If BCAAs act as signals of protein
      status, one would expect reduced food intake, avoidance of dietary protein, and
      reduction in neuropeptide expression in BCATm-KO mice. Instead, these mice
      exhibit an increased expression of orexigenic neuropeptides and an avoidance of
      BCAAs but not HP. These data thus suggest that either BCAAs do not act as
      physiological signals of protein status or the loss of BCAA metabolism within
      brain glia impairs the detection of protein balance.

PMID- 21969406
TI  - Cost-effectiveness of second-line antihyperglycemic therapy in patients with type
      2 diabetes mellitus inadequately controlled on metformin.
AB  - BACKGROUND: Metformin is widely accepted as first-line pharmacotherapy for
      patients with type 2 diabetes mellitus when glycemic control cannot be achieved
      by lifestyle interventions alone. However, uncertainty exists regarding the
      optimal second-line therapy for patients whose diabetes is inadequately
      controlled by metformin monotherapy. Increased use of newer, more costly agents,
      along with the rising incidence of type 2 diabetes, carries significant budgetary
      implications for health care systems. We conducted this analysis to determine the
      relative costs, benefits and cost-effectiveness of options for second-line
      treatment of type 2 diabetes. METHODS: We used the United Kingdom Prospective
      Diabetes Study Outcomes Model to forecast diabetes-related complications, quality
      adjusted life-years and costs of alternative second-line therapies available in
      Canada for adults with type 2 diabetes inadequately controlled by metformin. We
      obtained clinical data from a systematic review and mixed treatment comparison
      meta-analysis, and we obtained information on costs and utilities from published
      sources. We performed extensive sensitivity analyses to test the robustness of
      results to variation in inputs and assumptions. RESULTS: Sulphonylureas, when
      added to metformin, were associated with the most favourable cost-effectiveness
      estimate, with an incremental cost of $12 757 per quality-adjusted life-year
      gained, relative to continued metformin monotherapy. Treatment with other agents,
      including thiazolidinediones and dipeptidyl peptidase-4 inhibitors, had
      unfavourable cost-effectiveness estimates compared with sulphonylureas. These
      results were robust to extensive sensitivity analyses. INTERPRETATION: For most
      patients with type 2 diabetes that is inadequately controlled with metformin
      monotherapy, the addition of a sulphonylurea represents the most cost-effective
      second-line therapy.

PMID- 21969407
TI  - Antidepressants, antiplatelets and bleeding: one more thing to worry about?

PMID- 21969408
TI  - Tailored treatment for postpartum depression.

PMID- 21969409
TI  - Chronic cerebrospinal venous insufficiency: a Kuhnian paradigm shift or another
      fad?

PMID- 21969410
TI  - Brouhaha erupts over testosterone-testing advertising campaign.

PMID- 21969411
TI  - Association between chronic cerebrospinal venous insufficiency and multiple
      sclerosis: a meta-analysis.
AB  - BACKGROUND: It has been proposed by Zamboni and colleagues that multiple
      sclerosis is caused by chronic cerebrospinal venous insufficiency, a term used to
      describe ultrasound-detectable abnormalities in the anatomy and flow of intra-
      and extracerebral veins. We conducted a meta-analysis of studies that reported
      the frequency of chronic cerebrospinal venous insufficiency among patients with
      and those without multiple sclerosis. METHODS: We searched MEDLINE and EMBASE as
      well as bibliographies of relevant articles for eligible studies. We included
      studies if they used ultrasound to diagnose chronic cerebrospinal venous
      insufficiency and compared the frequency of the venous abnormalities among
      patients with and those without multiple sclerosis. RESULTS: We identified eight
      eligible studies: all included healthy controls, and four of them also included a
      control group of patients with neurologic diseases other than multiple sclerosis.
      Chronic cerebrospinal venous insufficiency was more frequent among patients with
      multiple sclerosis than among the healthy controls (odds ratio [OR] 13.5, 95%
      confidence interval [CI] 2.6-71.4), but there was extensive unexplained
      heterogeneity among the studies. The association remained significant in the most
      conservative sensitivity analysis (OR 3.7, 95% CI 1.2-11.0), in which we removed
      the initial study by Zamboni and colleagues and added a study that did not find
      chronic cerebrospinal venous insufficiency in any patient. Although chronic
      cerebrospinal venous insufficiency was also more frequent among patients with
      multiple sclerosis than among controls with other neurologic diseases (OR 32.5,
      95% CI 0.6-1775.7), the association was not statistically significant, the 95% CI
      was wide, and the OR was less extreme after removal of the study by Zamboni and
      colleagues (OR 3.5, 95% 0.8-15.8). INTERPRETATION: Our findings showed a positive
      association between chronic cerebrospinal venous insufficiency and multiple
      sclerosis. However, poor reporting of the success of blinding and marked
      heterogeneity among the studies included in our review precluded definitive
      conclusions.

PMID- 21969412
TI  - Boilerplate being tested for clinical trials agreements.

PMID- 21969414
TI  - Back to black bag and horse-and-buggy medicine.

PMID- 21969415
TI  - Syphilitic chancre of the mouth.

PMID- 21969417
TI  - Even an editor needs an editor: reflections after five years at CMAJ.

PMID- 21969418
TI  - Prevention of posttraumatic stress disorder by early treatment: results from the
      Jerusalem Trauma Outreach And Prevention study.
AB  - CONTEXT: Preventing posttraumatic stress disorder (PTSD) is a pressing public
      health need. OBJECTIVES: To compare early and delayed exposure-based, cognitive,
      and pharmacological interventions for preventing PTSD. DESIGN: Equipoise
      stratified randomized controlled study. SETTING: Hadassah Hospital unselectively
      receives trauma survivors from Jerusalem and vicinity. PARTICIPANTS:
      Consecutively admitted survivors of traumatic events were assessed by use of
      structured telephone interviews a mean (SD) 9.61 (3.91) days after the traumatic
      event. Survivors with symptoms of acute stress disorder were referred for
      clinical assessment. Survivors who met PTSD symptom criteria during the clinical
      assessment were invited to receive treatment. INTERVENTIONS: Twelve weekly
      sessions of prolonged exposure (PE; n = 63), or cognitive therapy (CT; n = 40),
      or double blind treatment with 2 daily tablets of either escitalopram (10 mg) or
      placebo (selective serotonin reuptake inhibitor/placebo; n = 46), or 12 weeks in
      a waiting list group (n = 93). Treatment started a mean (SD) 29.8 (5.7) days
      after the traumatic event. Waiting list participants with PTSD after 12 weeks
      received PE a mean (SD) 151.8 (42.4) days after the traumatic event (delayed PE).
      MAIN OUTCOME MEASURE: Proportion of participants with PTSD after treatment, as
      determined by the use of the Clinician-Administered PTSD Scale (CAPS) 5 and 9
      months after the traumatic event. Treatment assignment and attendance were
      concealed from the clinicians who used the CAPS. RESULTS: At 5 months, 21.6% of
      participants who received PE and 57.1% of comparable participants on the waiting
      list had PTSD (odds ratio [OR], 0.21 [95% CI, 0.09-0.46]). At 5 months, 20.0% of
      participants who received CT and 58.7% of comparable participants on the waiting
      list had PTSD (OR, 0.18 [CI, 0.06-0.48]). The PE group did not differ from the CT
      group with regard to PTSD outcome (OR, 0.87 [95% CI, 0.29-2.62]). The PTSD
      prevalence rates did not differ between the escitalopram and placebo subgroups
      (61.9% vs 55.6%; OR, 0.77 [95% CI, 0.21-2.77]). At 9 months, 20.8% of
      participants who received PE and 21.4% of participants on the waiting list had
      PTSD (OR, 1.04 [95% CI, 0.40-2.67]). Participants with partial PTSD before
      treatment onset did similarly well with and without treatment. CONCLUSIONS:
      Prolonged exposure, CT, and delayed PE effectively prevent chronic PTSD in recent
      survivors. The lack of improvement from treatment with escitalopram requires
      further evaluation. Trauma-focused clinical interventions have no added benefit
      to survivors with subthreshold PTSD symptoms. Trial Registration
      clinicaltrials.gov Identifier: NCT00146900.

PMID- 21969420
TI  - Randomized trial to evaluate the efficacy of cognitive therapy for low
      functioning patients with schizophrenia.
AB  - CONTEXT: Low-functioning patients with chronic schizophrenia have high direct
      treatment costs and indirect costs incurred due to lost employment and
      productivity and have a low quality of life; antipsychotic medications and
      psychosocial interventions have shown limited efficacy to promote improved
      functional outcomes. OBJECTIVE: To determine the efficacy of an 18-month recovery
      oriented cognitive therapy program to improve psychosocial functioning and
      negative symptoms (avolition-apathy, anhedonia-asociality) in low-functioning
      patients with schizophrenia. Design, Setting, and PARTICIPANTS: A single-center,
      18-month, randomized, single-blind, parallel group trial enrolled 60 low
      functioning, neurocognitively impaired patients with schizophrenia (mean age,
      38.4 years; 33.3% female; 65.0% African American). INTERVENTIONS: Cognitive
      therapy plus standard treatment vs standard treatment alone. MAIN OUTCOME
      MEASURES: The primary outcome measure was the Global Assessment Scale score at 18
      months after randomization. The secondary outcomes were scores on the Scale for
      the Assessment of Negative Symptoms and the Scale for the Assessment of Positive
      Symptoms at 18 months after randomization. RESULTS: Patients treated with
      cognitive therapy showed a clinically significant mean improvement in global
      functioning from baseline to 18 months that was greater than the improvement seen
      with standard treatment (within-group Cohen d, 1.36 vs 0.06, respectively;
      adjusted mean [SE], 58.3 [3.30] vs 47.9 [3.60], respectively; P = .03; between
      group d = 0.56). Patients receiving cognitive therapy as compared with those
      receiving standard treatment also showed a greater mean reduction in avolition
      apathy (adjusted mean [SE], 1.66 [0.31] vs 2.81 [0.34], respectively; P = .01;
      between-group d = -0.66) and positive symptoms (hallucinations, delusions,
      disorganization) (adjusted mean [SE], 9.4 [3.3] vs 18.2 [3.8], respectively; P =
      .04; between-group d = -0.46) at 18 months. Age was controlled in the analyses,
      and there were no meaningful group differences in baseline antipsychotic
      medications (class or dosage) or in medication changes during the course of the
      trial. CONCLUSION: Cognitive therapy can be successful in promoting clinically
      meaningful improvements in functional outcome, motivation, and positive symptoms
      in low-functioning patients with significant cognitive impairment. Trial
      Registration  clinicaltrials.gov Identifier: NCT00350883.

PMID- 21969421
TI  - Cognitive therapy for negative symptoms of schizophrenia.

PMID- 21969419
TI  - Anterior cingulate cortex gamma-aminobutyric acid in depressed adolescents:
      relationship to anhedonia.
AB  - CONTEXT: Anhedonia, a core symptom of major depressive disorder (MDD) and highly
      variable among adolescents with MDD, may involve alterations in the major
      inhibitory amino acid neurotransmitter system of gamma-aminobutyric acid (GABA).
      OBJECTIVE: To test whether anterior cingulate cortex (ACC) GABA levels, measured
      by proton magnetic resonance spectroscopy, are decreased in adolescents with MDD.
      The associations of GABA alterations with the presence and severity of anhedonia
      were explored. DESIGN: Case-control, cross-sectional study using single-voxel
      proton magnetic resonance spectroscopy at 3 T. SETTING: Two clinical research
      divisions at 2 teaching hospitals. PARTICIPANTS: Twenty psychotropic medication
      free adolescents with MDD (10 anhedonic, 12 female, aged 12-19 years) with
      episode duration of 8 weeks or more and 21 control subjects group matched for sex
      and age. MAIN OUTCOME MEASURES: Anterior cingulate cortex GABA levels expressed
      as ratios relative to unsuppressed voxel tissue water (w) and anhedonia scores
      expressed as a continuous variable. RESULTS: Compared with control subjects,
      adolescents with MDD had significantly decreased ACC GABA/w (t = 3.2; P < .003).
      When subjects with MDD were categorized based on the presence of anhedonia, only
      anhedonic patients had decreased GABA/w levels compared with control subjects (t
      = 4.08; P < .001; P(Tukey) < .001). Anterior cingulate cortex GABA/w levels were
      negatively correlated with anhedonia scores for the whole MDD group (r = -0.50; P
      = .02), as well as for the entire participant sample including the control
      subjects (r = -0.54; P < .001). Anterior cingulate cortex white matter was also
      significantly decreased in adolescents with MDD compared with controls (P = .04).
      CONCLUSIONS: These findings suggest that GABA, the major inhibitory
      neurotransmitter in the brain, may be implicated in adolescent MDD and, more
      specifically, in those with anhedonia. In addition, use of a continuous rather
      than categorical scale of anhedonia, as in the present study, may permit greater
      specificity in evaluating this important clinical feature.

PMID- 21969422
TI  - Assessment of pedophilia using hemodynamic brain response to sexual stimuli.
AB  - CONTEXT: Accurately assessing sexual preference is important in the treatment of
      child sex offenders. Phallometry is the standard method to identify sexual
      preference; however, this measure has been criticized for its intrusiveness and
      limited reliability. OBJECTIVE: To evaluate whether spatial response pattern to
      sexual stimuli as revealed by a change in the blood oxygen level-dependent signal
      facilitates the identification of pedophiles. DESIGN: During functional magnetic
      resonance imaging, pedophilic and nonpedophilic participants were briefly exposed
      to same- and opposite-sex images of nude children and adults. We calculated
      differences in blood oxygen level-dependent signals to child and adult sexual
      stimuli for each participant. The corresponding contrast images were entered into
      a group analysis to calculate whole-brain difference maps between groups. We
      calculated an expression value that corresponded to the group result for each
      participant. These expression values were submitted to 2 different classification
      algorithms: Fisher linear discriminant analysis and kappa -nearest neighbor
      analysis. This classification procedure was cross-validated using the leave-one
      out method. SETTING: Section of Sexual Medicine, Medical School, Christian
      Albrechts University of Kiel, Kiel, Germany. PARTICIPANTS: We recruited 24
      participants with pedophilia who were sexually attracted to either prepubescent
      girls (n = 11) or prepubescent boys (n = 13) and 32 healthy male controls who
      were sexually attracted to either adult women (n = 18) or adult men (n = 14).
      MAIN OUTCOME MEASURES: Sensitivity and specificity scores of the 2 classification
      algorithms. RESULTS: The highest classification accuracy was achieved by Fisher
      linear discriminant analysis, which showed a mean accuracy of 95% (100%
      specificity, 88% sensitivity). CONCLUSIONS: Functional brain response patterns to
      sexual stimuli contain sufficient information to identify pedophiles with high
      accuracy. The automatic classification of these patterns is a promising objective
      tool to clinically diagnose pedophilia.

PMID- 21969423
TI  - Long-term bisphosphonate usage and subtrochanteric insufficiency fractures: a
      cause for concern?
AB  - For over a decade, bisphosphonate administration has evolved and become the
      cornerstone of the prevention and treatment of fragility fractures. Millions of
      post-menopausal women have relied on, and continue to depend on, the long-acting,
      bone density-maintaining pharmaceutical drug to prevent low-energy fractures. In
      return, we have seen the number of fragility fractures decrease, along with
      associated costs and emotional benefits. However, with any drug, there are often
      concerns with side effects and complications, and this unique drug class is
      seeing one such complication in atypical subtrochanteric femoral fracture,
      counterproductive to that which it was designed to prevent. This has created
      concern over long-term bisphosphonate administration and its potential link to
      these atypical fractures. There is controversial evidence surrounding such a
      definitive link, and no protocol for managing these fractures.  This review
      offers the latest information regarding this rare but increasingly controversial
      adverse effect and its potential connection to one of the most successful forms
      of treatment that is available for the management of fragility fractures.

PMID- 21969424
TI  - Robotic systems in orthopaedic surgery.
AB  - Robots have been used in surgery since the late 1980s. Orthopaedic surgery began
      to incorporate robotic technology in 1992, with the introduction of ROBODOC, for
      the planning and performance of total hip replacement. The use of robotic systems
      has subsequently increased, with promising short-term radiological outcomes when
      compared with traditional orthopaedic procedures. Robotic systems can be
      classified into two categories: autonomous and haptic (or surgeon-guided).
      Passive surgery systems, which represent a third type of technology, have also
      been adopted recently by orthopaedic surgeons. While autonomous systems have
      fallen out of favour, tactile systems with technological improvements have become
      widely used. Specifically, the use of tactile and passive robotic systems in
      unicompartmental knee replacement (UKR) has addressed some of the historical
      mechanisms of failure of non-robotic UKR. These systems assist with increasing
      the accuracy of the alignment of the components and produce more consistent
      ligament balance. Short-term improvements in clinical and radiological outcomes
      have increased the popularity of robot-assisted UKR. Robot-assisted orthopaedic
      surgery has the potential for improving surgical outcomes. We discuss the
      different types of robotic systems available for use in orthopaedics and consider
      the indication, contraindications and limitations of these technologies.

PMID- 21969425
TI  - Ischiofemoral impingement.
AB  - Femoroacetabular impingement is a well-documented cause of hip pain. There is,
      however, increasing evidence for the presence of a previously unrecognised
      impingement-type condition around the hip - ischiofemoral impingement. This is
      caused by abnormal contact between the lesser trochanter of the femur and the
      ischium, and presents as atypical groin and/or posterior buttock pain. The
      symptoms are gradual in onset and may be similar to those of iliopsoas
      tendonitis, hamstring injury or bursitis. The presence of ischiofemoral
      impingement may be indicated by pain caused by a combination of hip extension,
      adduction and external rotation. Magnetic resonance imaging demonstrates
      inflammation and oedema in the ischiofemoral space and quadratus femoris, and is
      distinct from an acute tear. To date this has only appeared in the specialist
      orthopaedic literature as a problem that has developed after total hip
      replacement, not in the unreplaced joint.

PMID- 21969426
TI  - The prevalence of cam-type femoroacetabular deformity in asymptomatic adults.
AB  - We performed a retrospective examination of the anteroposterior pelvic CT scout
      views of 419 randomly selected patients between April 2004 and August 2009 in
      order to determine the prevalence of cam-type femoroacetabular deformity in the
      asymptomatic population. The CT scans had all been undertaken for conditions
      unrelated to disorders of the hip. The frequency of cam-type femoroacetabular
      deformity was assessed by measuring the alpha-angle of each hip on the
      anteroposterior images. The alpha-angles were classified according to the
      Copenhagen Osteoarthritis Study. Among 215 male hips (108 patients) the mean
      alpha-angle was 59.12 degrees  (37.75 degrees  to 103.50 degrees ). Of these, a
      total of 30 hips (13.95%) were defined as pathological, 32 (14.88%) as borderline
      and 153 (71.16%) as normal. Among 540 female hips (272 patients) the mean alpha
      angle was 45.47 degrees  (34.75 degrees  to 87.00 degrees ), with 30 hips (5.56%)
      defined as pathological, 33 (6.11%) as borderline and 477 (88.33%) as normal. It
      appears that the cam-type femoroacetabular deformity is not rare among the
      asymptomatic population. These anatomical abnormalities, as determined by an
      increased alpha-angle, appear to be twice as frequent in men as in women.
      Although an association between osteoarthritis and femoroacetabular impingement
      is believed to exist, a long-term epidemiological study is needed to determine
      the natural history of these anatomical abnormalities.

PMID- 21969427
TI  - Sensitivity and specificity of blood cobalt and chromium metal ions for
      predicting failure of metal-on-metal hip replacement.
AB  - Blood metal ions have been widely used to investigate metal-on-metal hip
      replacements, but their ability to discriminate between well-functioning and
      failed hips is not known. The Medicines and Healthcare products Regulatory Agency
      (MHRA) has suggested a cut-off level of 7 parts per billion (ppb). We performed a
      pair-matched, case-control study to investigate the sensitivity and specificity
      of blood metal ion levels for diagnosing failure in 176 patients with a
      unilateral metal-on-metal hip replacement. We recruited 88 cases with a pre
      revision, unexplained failed hip and an equal number of matching controls with a
      well-functioning hip. We investigated the 7 ppb cut-off level for the maximum of
      cobalt or chromium and determined optimal mathematical cut-off levels from
      receiver-operating characteristic curves. The 7 ppb cut-off level for the maximum
      of cobalt or chromium had a specificity of 89% and sensitivity 52% for detecting
      a pre-operative unexplained failed metal on metal hip replacement. The optimal
      cut-off level for the maximum of cobalt or chromium was 4.97 ppb and had
      sensitivity 63% and specificity 86%. Blood metal ions had good discriminant
      ability to separate failed from well-functioning hip replacements. The MHRA cut
      off level of 7 ppb provides a specific test but has poor sensitivity.

PMID- 21969428
TI  - Free vascularised fibular graft for post-traumatic osteonecrosis of the femoral
      head in teenage patients.
AB  - Free vascularised fibular grafting has been reported to be successful for adult
      patients with osteonecrosis of the femoral head (ONFH). However, its benefit in
      teenage patients with post-traumatic ONFH has not been determined. We evaluated
      the effectiveness of free vascularised fibular grafting in the treatment of this
      condition in children and adolescents. We retrospectively analysed 28 hips in 28
      patients in whom an osteonecrotic femoral head had been treated with free
      vascularised fibular grafting between 2002 and 2008. Their mean age was 16.3
      years (13 to 19). The stage of the disease at time of surgery, and results of
      treatment including pre- and post-operative Harris hip scores, were studied. We
      defined clinical failure as conversion to total hip replacement. All patients
      were followed up for a mean of four years (2 to 7). The mean Harris hip score
      improved from 60.4 (37 to 84) pre-operatively to 94.2 (87 to 100) at final follow
      up. At the latest follow-up we found improved or unchanged radiographs in all
      four initially stage II hips and in 23 of 24 stage III or IV hips. Only one hip
      (stage V) deteriorated. No patient underwent total hip replacement. Free
      vascularised fibular grafting is indicated for the treatment of post-traumatic
      ONFH in teenage patients.

PMID- 21969429
TI  - Femoral revision with the Wagner tapered stem: a ten- to 15-year follow-up study.
AB  - Revision after failed femoral components may be technically demanding due to loss
      of peri-prosthetic bone. This retrospective study evaluated the long-term results
      of femoral revision using the cementless Wagner Self-Locking stem. Between 1992
      and 1998, 68 consecutive hips in 66 patients underwent femoral revision using
      this implant. A total of 25 patients died from unrelated causes without further
      revision; the remaining 41 hips in 41 patients (12 men and 29 women) with a mean
      age of 61 years (29 to 80) were reviewed at a mean follow-up of 13.9 years (10.4
      to 15.8). A transfemoral approach was used in 32 hips. A total of five stems
      required further revision because of infection in two, progressive subsidence in
      two and recurrent dislocation in one. Four hips had dislocated and eight stems
      had subsided >= 10 mm. The mean Harris hip score improved from 33 points pre
      operatively to 75 points at final follow-up (p < 0.001). In all, 33 stems (91.7%)
      showed radiological signs of stable bone fixation. The cumulative survival rates
      at 15.8 years with femoral revision for any reason and for stem failure as the
      endpoints were 92.0% (95% confidence interval (CI) 86.0% to 98.4%) and 96.6% (95%
      CI 92.2% to 100%), respectively. The survivorship with revision and >= 10 mm
      migration of the stem as the endpoint was 83.6% (95% CI 76.6% to 91.4%). This
      study shows quite good survival and moderate clinical outcome when using a
      monoblock tapered titanium stem for supporting the regeneration of bone in
      complex revision hip surgery.

PMID- 21969430
TI  - The burden of arthroscopy of the knee: a contemporary analysis of data from the
      English NHS.
AB  - Arthroscopy of the knee is one of the most commonly performed orthopaedic
      procedures worldwide. Large-volume outcome data have not previously been
      available for English NHS patients. Prospectively collected admissions data,
      routinely collected on every English NHS patient, were analysed to determine the
      rates of complications within 30 days (including re-operation and re-admission),
      90-day symptomatic venous thromboembolism and all-cause mortality. There were
      301,701 operations performed between 2005 and 2010--an annual incidence of 9.9
      per 10,000 English population. Of these, 16,552 (6%) underwent ligament
      reconstruction and 106,793 (35%) underwent meniscal surgery. The 30-day re
      admission rate was 0.64% (1662) and 30-day wound complication rate was 0.26%
      (677). The overall 30-day re-operation rate was 0.40% (1033) and the 90-day
      pulmonary embolism rate was 0.08% (230), of which six patients died. 90-day
      mortality was 0.02% (47). Age < 40 years, male gender and ligament reconstruction
      were significantly associated with an increased rate of 30-day re-admission and
      unplanned re-operation. In addition, a significant increase in 30-day admission
      rates were seen with Charlson comorbidity scores of 1 (p = 0.037) and >= 2 (p <
      0.001) compared with scores of 0, and medium volume units compared with high
      volume units (p < 0.001). Complications following arthroscopy of the knee are
      rare. It is a safe procedure, which in the majority of cases is performed as day
      case surgery. These data can be used for quality benchmarking, in terms of
      consent, consultant re-validation and individual unit performance.

PMID- 21969431
TI  - Single bundle anterior cruciate reconstruction does not restore normal knee
      kinematics at six months: an upright MRI study.
AB  - Abnormal knee kinematics following reconstruction of the anterior cruciate
      ligament may exist despite an apparent resolution of tibial laxity and functional
      benefit. We performed upright, weight-bearing MR scans of both knees in the
      sagittal plane at different angles of flexion to determine the kinematics of the
      knee following unilateral reconstruction (n = 12). The uninjured knee acted as a
      control. Scans were performed pre-operatively and at three and six months post
      operatively. Anteroposterior tibial laxity was determined using an arthrometer
      and patient function by validated questionnaires before and after reconstruction.
      In all the knees with deficient anterior cruciate ligaments, the tibial plateau
      was displaced anteriorly and internally rotated relative to the femur when
      compared with the control contralateral knee, particularly in extension and early
      flexion (mean lateral compartment displacement: extension 7.9 mm (sd 4.8), p =
      0.002 and 30 degrees  flexion 5.1 mm (sd 3.6), p = 0.004). In all ten patients
      underwent post-operative scans. Reconstruction reduced the subluxation of the
      lateral tibial plateau at three months, with resolution of anterior displacement
      in early flexion, but not in extension (p = 0.015). At six months, the
      reconstructed knee again showed anterior subluxation in both the lateral (mean:
      extension 4.2 mm (sd 4.2), p = 0.021 and 30 degrees  flexion 3.2 mm (sd 3.3), p =
      0.024) and medial compartments (extension, p = 0.049).  Our results show that
      despite improvement in laxity and functional benefit, abnormal knee kinematics
      remain at six months and actually deteriorate from three to six months following
      reconstruction of the anterior cruciate ligament.

PMID- 21969432
TI  - The patho-anatomy of patellofemoral subluxation.
AB  - Patella subluxation assessed on dynamic MRI has previously been shown to be
      associated with anterior knee pain. In this MRI study of 60 patients we
      investigated the relationship between subluxation and multiple bony,
      cartilaginous and soft-tissue factors that might predispose to subluxation using
      discriminant function analysis. Patella engagement (% of patella cartilage
      overlapping with trochlea cartilage) had the strongest relationship with
      subluxation. Patellae with > 30% engagement tended not to sublux; those with <
      30% tended to sublux. Other factors that were associated with subluxation
      included the tibial tubercle-trochlea notch distance, vastus medialis obliquus
      distance from patella, patella alta, and the bony and cartilaginous sulcus angles
      in the superior part of the trochlea. No relationship was found between
      subluxation and sulcus angles for cartilage and bone in the middle and lower part
      of the trochlea, cartilage thicknesses and Wiberg classification of the patella.
      This study indicates that patella engagement is a key factor associated with
      patellar subluxation. This suggests that in patients with anterior knee pain with
      subluxation, resistant to conservative management, surgery directed towards
      improving patella engagement should be considered. A clinical trial is necessary
      to test this hypothesis.

PMID- 21969433
TI  - The influence of malrotation and femoral component material on patellofemoral
      wear during gait.
AB  - Complications involving the patellofemoral joint, caused by malrotation of the
      femoral component during total knee replacement, are an important cause of
      persistent pain and failure leading to revision surgery. The aim of this study
      was to determine and quantify the influence of femoral component malrotation on
      patellofemoral wear, and to determine whether or not there is a difference in the
      rate of wear of the patellar component when articulated against oxidised
      zirconium (OxZr) and cobalt-chrome (CoCr) components. An in vitro method was used
      to simulate patellar maltracking for both materials. Both rates of wear and
      changes in height on the patellar articular surface were measured. The mean rates
      of wear measured were very small compared to standard tibiofemoral wear rates.
      When data for each femoral component material were pooled, the mean rate of wear
      was 0.19 mm3/Mcycle (sd 0.21) for OxZr and 0.34 mm3/Mcycle (sd 0.335) for CoCr.
      The largest change in height on each patella varied from -0.05 mm to -0.33 mm
      over the different configurations. The results suggest that patellar maltracking
      due to an internally rotated femoral component leads to an increased mean
      patellar wear. Although not statistically significant, the mean wear production
      may be lower for OxZr than for CoCr components.

PMID- 21969434
TI  - Femoral component loosening in high-flexion total knee replacement: an in vitro
      comparison of high-flexion versus conventional designs.
AB  - High-flexion total knee replacement (TKR) designs have been introduced to improve
      flexion after TKR. Although the early results of such designs were promising,
      recent literature has raised concerns about the incidence of early loosening of
      the femoral component. We compared the minimum force required to cause femoral
      component loosening for six high-flexion and six conventional TKR designs in a
      laboratory experiment. Each TKR design was implanted in a femoral bone model and
      placed in a loading frame in 135 degrees  of flexion. Loosening of the femoral
      component was induced by moving the tibial component at a constant rate of
      displacement while maintaining the same angle of flexion. A stereophotogrammetric
      system registered the relative movement between the femoral component and the
      underlying bone until loosening occurred. Compared with high-flexion designs,
      conventional TKR designs required a significantly higher force before loosening
      occurred (p < 0.001). High-flexion designs with closed box geometry required
      significantly higher loosening forces than high-flexion designs with open box
      geometry (p = 0.0478). The presence of pegs further contributed to the fixation
      strength of components. We conclude that high-flexion designs have a greater risk
      for femoral component loosening than conventional TKR designs. We believe this is
      attributable to the absence of femoral load sharing between the prosthetic
      component and the condylar bone during flexion.

PMID- 21969435
TI  - The non-operative functional management of patients with a rupture of the tendo
      Achillis leads to low rates of re-rupture.
AB  - Controversy surrounds the most appropriate treatment method for patients with a
      rupture of the tendo Achillis. The aim of this study was to assess the long term
      rate of re-rupture following management with a non-operative functional protocol.
      We report the outcome of 945 consecutive patients (949 tendons) diagnosed with a
      rupture of the tendo Achillis managed between 1996 and 2008. There were 255
      female and 690 male patients with a mean age of 48.97 years (12 to 86). Delayed
      presentation was defined as establishing the diagnosis and commencing treatment
      more than two weeks after injury. The overall rate of re-rupture was 2.8% (27 re
      ruptures), with a rate of 2.9%  (25 re-ruptures) for those with an acute
      presentation and 2.7% (two re-ruptures) for those with delayed presentation. 
      This study of non-operative functional management of rupture of the tendo
      Achillis is the largest of its kind in the literature. Our rates of re-rupture
      are similar to, or better than, those published for operative treatment. We
      recommend our regime for patients of all ages and sporting demands, but it is
      essential that they adhere to the protocol.

PMID- 21969436
TI  - Corrective supramalleolar osteotomy for malunited pronation-external rotation
      fractures of the ankle.
AB  - We undertook a prospective study to analyse the outcome of 48 malunited pronation
      external rotation fractures of the ankle in 48 patients (25 females and 23 males)
      with a mean age of 45 years (21 to 69), treated by realignment osteotomies. The
      interval between the injury and reconstruction was a mean of 20.2 months (3 to
      98).  In all patients, valgus malalignment of the distal tibia and malunion of
      the fibula were corrected. In some patients, additional osteotomies were
      performed. Patients were reviewed regularly, and the mean follow-up was 7.1 years
      (2 to 15).  Good or excellent results were obtained in 42 patients (87.5%) with
      the benefit being maintained over time. Congruent ankles without a tilted talus
      (Takakura stage 0 and 1) were obtained in all but five cases. One patient
      required total ankle replacement.

PMID- 21969437
TI  - The sentinel vein: an anatomical guide to localisation of the dorsomedial
      cutaneous nerve in hallux surgery.
AB  - Damage to the dorsomedial branch of the medial dorsal cutaneous nerve is not
      uncommon in surgery of the hallux. The resultant morbidity can be disabling. In
      the light of the senior author's operative observation of a sentinel vein, we
      undertook a cadaver study to investigate the anatomical relationships of the
      dorsomedial branch of the medial dorsal cutaneous nerve. This established that in
      14 of 16 cadaver great toes exposed via a modified medial incision, there is an
      easily identified vein which runs transversely superficial and proximal to the
      nerve. In a prospective clinical study of 171 operations on the great toe using
      this approach, we confirmed this anatomical relationship in 142 procedures (83%),
      with no complaint of numbness or pain in the scar at follow-up. We attribute this
      to careful identification of the 'sentinel' vein and the subjacent sensory nerve,
      which had been successfully protected from damage. We recommend this technique
      when operating on the great toe.

PMID- 21969438
TI  - Treatment of frozen shoulder by manipulation under anaesthetic and injection:
      does the timing of treatment affect the outcome?
AB  - The effect of timing of a manipulation under anaesthetic (MUA) and injection of
      corticosteroid and local anaesthetic for the treatment of frozen shoulder has
      attracted little attention to date. All studies describe a period of conservative
      treatment before proceeding to an MUA. Delay has been associated with a poorer
      outcome. We present a retrospective review of a prospectively collected, single
      surgeon, consecutive series of 246 patients with a primary frozen shoulder
      treated by MUA within four weeks of presentation. The mean duration of presenting
      symptoms was 28 weeks (6 to 156), and time to initial post-operative assessment
      was 26 days (5 to 126). The Oxford shoulder score (OSS) improved by a mean of 16
      points (Wilcoxon signed-ranks test, p < 0.001) with a mean OSS at this time of 43
      (7 to 48). Linear regression analysis showed no correlation between the duration
      of presenting symptoms and OSS at initial follow-up  (R2 < 0.001) or peri
      operative change in OSS (R2 < 0.001) or OSS at long-term follow-up  (R2 < 0.03).
      Further analysis at a mean of 42 months (8 to 127) revealed a sustained
      improvement with a mean OSS of 44 (16 to 48). A good outcome follows an MUA and
      injection of corticosteroid and local anaesthetic in patients with primary frozen
      shoulder, independent of the duration of the presenting symptoms, and this
      improvement is maintained in the long term.

PMID- 21969439
TI  - Allograft-prosthesis composite reconstruction for the management of failed elbow
      replacement with massive structural bone loss: a medium-term follow-up.
AB  - We studied, ten patients (11 elbows) who had undergone 14 allograft-prosthesis
      composite reconstructions following failure of a previous total elbow replacement
      with massive structural bone loss. There were nine women and one man with a mean
      age of 64 years (40 to 84), who were reviewed at a mean of 75 months (24 to 213).
      One patient developed a deep infection after 26 months and had the allograft
      prosthesis composite removed, and two patients had mild pain. The median flexion
      extension arc was 100 degrees  (95% confidence interval (CI) 76 degrees  to 124
      degrees ). With the exception of the patient who had the infected failure, all
      the patients could use their elbows comfortably without splints or braces for
      activities of daily living. The mean Mayo Elbow Performance Index improved from
      9.5 (95% CI 4.4 to 14.7) pre-operatively to 74 (95% CI 62.4 to 84.9) at final
      review. Radiologically, the rate of partial resorption was similar in the humeral
      and ulnar allografts (three of six and four of eight, respectively; p > 0.999).
      The patterns of resorption, however, were different. Union at the host-bone
      allograft junction was also different between the humeral and ulnar allografts
      (one of six and seven of eight showing union, respectively; p = 0.03). At medium
      term follow-up, allograft-prosthesis composite reconstruction appears to be a
      useful salvage technique for failed elbow replacements with massive bone loss.
      The effects of allograft resorption and host-bone-allograft junctional union on
      the longevity of allograft-prosthesis composite reconstruction, however, remain
      unknown, and it is our view that these patients should remain under long-term
      regular review.

PMID- 21969440
TI  - The intra-operative radius joystick test to diagnose complete disruption of the
      interosseous membrane.
AB  - Disruption of the interosseous membrane is easily missed in patients with Essex
      Lopresti syndrome. None of the imaging techniques available for diagnosing
      disruption of the interosseous membrane are completely dependable. We undertook
      an investigation to identify whether a simple intra-operative test could be used
      to diagnose disruption of the interosseous membrane during surgery for fracture
      of the radial head and to see if the test was reproducible. We studied 20
      cadaveric forearms after excision of the radial head, ten with and ten without
      disruption of the interosseous membrane. On each forearm, we performed the radius
      joystick test: moderate lateral traction was applied to the radial neck with the
      forearm in maximal pronation, to look for lateral displacement of the proximal
      radius indicating that the interosseous membrane had been disrupted. Each of six
      surgeons (three junior and three senior) performed the test on two consecutive
      days. Intra-observer agreement was 77% (95% confidence interval (CI) 67 to 85)
      and interobserver agreement was 97% (95% CI 92 to 100). Sensitivity was 100% (95%
      CI 97 to 100), specificity 88% (95% CI 81 to 93), positive predictive value 90%
      (95% CI 83 to 94), and negative predictive value 100%). This cadaveric study
      suggests that the radius joystick test may be useful for detecting disruption of
      the interosseous membrane in patients undergoing open surgery for fracture of the
      radial head and is reproducible. A confirmatory study in vivo is now required.

PMID- 21969441
TI  - CT scan assessment of the pathway of the true lateral approach for transforaminal
      endoscopic lumbar discectomy: is It possible?
AB  - We performed a prospective study to examine the influence of the patient's
      position on the location of the abdominal organs, to investigate the possibility
      of a true lateral approach for transforaminal endoscopic lumbar discectomy. Pre
      operative abdominal CT scans were taken in 20 patients who underwent endoscopic
      lumbar discectomy. Axial images in parallel planes of each intervertebral disc
      from L1 to L5 were achieved in both supine and prone positions. The most
      horizontal approach angles possible to avoid injury to the abdominal organs were
      measured. The results demonstrated that the safe approach angles were
      significantly less (i.e., more horizontal) in the prone than in the supine
      position. Obstacles to a more lateral approach were mainly the liver, the spleen
      and the kidneys at L1/2 (39 of 40, 97.5%) and L2/3 (28 of 40, 70.0%), and the
      intestines at L3/4 (33 of 40, 82.5%) and L4/5 (30 of 30, 100%). A true lateral
      approach from each side was possible for 30 of the 40 discs at L3/4 (75%) and 23
      of the 30 discs at L4/5 (76.7%). We concluded that a more horizontal approach for
      transforaminal endoscopic lumbar discectomy is possible in the prone position but
      not in the supine. Prone abdominal CT is more helpful in determining the
      trajectory of the endoscope. While a true lateral approach is feasible in many
      patients, our study shows it is not universally applicable.

PMID- 21969442
TI  - Differences in post-operative functional disability and patient satisfaction
      between patients with long (three levels or more) and short (less than three)
      lumbar fusions.
AB  - We examined the differences in post-operative functional disability and patient
      satisfaction between 56 patients who underwent a lumbar fusion at three or more
      levels for degenerative disease (group I) and 69 patients, matched by age and
      gender, who had undergone a one or two level fusion (group II). Their mean age
      was 66 years (49 to 84) and the mean follow-up was 43 months (24 to 65). The mean
      pre-operative Oswestry Disability Index (ODI) and visual analogue scale (VAS) for
      back and leg pain, and the mean post-operative VAS were similar in both groups (p
      > 0.05), but post-operatively the improvement in ODI was significantly less in
      group I (40.6%) than in group II (49.5%) (p < 0.001). Of the ten ODI items,
      patients in group I showed significant problems with lifting, sitting, standing,
      and travelling (p < 0.05). The most significant differences in the post-operative
      ODI were observed between patients who had undergone fusion at four or more
      levels and those who had undergone fusion at less than four levels (p = 0.005).
      The proportion of patients who were satisfied with their operations was similar
      in groups I and II (72.7% and 77.0%, respectively) (p = 0.668). The mean number
      of fused levels was associated with the post-operative ODI (r = 0.266, p =
      0.003), but not with the post-operative VAS or satisfaction grade (p > 0.05).
      Post-operative functional disability was more severe in those with a long-level
      lumbar fusion, particularly at four or more levels, but patient satisfaction
      remained similar for those with both long- and short-level fusions.

PMID- 21969443
TI  - Does cementing the femoral component increase the risk of peri-operative
      mortality for patients having replacement surgery for a fracture of the neck of
      femur? Data from the National Hip Fracture Database.
AB  - Concerns have been reported to the United Kingdom National Patient Safety Agency,
      warning that cementing the femoral component during hip replacement surgery for
      fracture of the proximal femur may increase peri-operative mortality. The
      National Hip Fracture Database collects demographic and outcome data about
      patients with a fracture of the proximal femur from over 100 participating
      hospitals in the United Kingdom. We conducted a mixed effects logistic regression
      analysis of this dataset to determine whether peri-operative mortality was
      increased in patients who had undergone either hemiarthroplasty or total hip
      replacement using a cemented femoral component. A total of 16,496 patients from
      129 hospitals were included in the analysis, which showed a small but significant
      adjusted survival benefit associated with cementing (odds ratio 0.83, 95%
      confidence interval 0.72 to 0.96). Other statistically significant variables in
      predicting death at discharge, listed in order of magnitude of effect, were
      gender, American Society of Anesthesiologists grade, age, walking accompanied
      outdoors and arthroplasty. Interaction terms between cementing and these other
      variables were sequentially added to, but did not improve, the model. This study
      has not shown an increase in peri-operative mortality as a result of cementing
      the femoral component in patients requiring hip replacement following fracture of
      the proximal femur.

PMID- 21969444
TI  - Age at hip or knee joint replacement surgery predicts likelihood of revision
      surgery.
AB  - We compared revision and mortality rates of 4668 patients undergoing primary
      total hip and knee replacement between 1989 and 2007 at a University Hospital in
      New Zealand. The mean age at the time of surgery was 69 years (16 to 100). A
      total of 1175 patients (25%) had died at follow-up at a mean of ten years post
      operatively. The mean age of those who died within ten years of surgery was 74.4
      years (29 to 97) at time of surgery. No change in comorbidity score or age of the
      patients receiving joint replacement was noted during the study period. No
      association of revision or death could be proven with higher comorbidity scoring,
      grade of surgeon, or patient gender. We found that patients younger than 50 years
      at the time of surgery have a greater chance of requiring a revision than of
      dying, those around 58 years of age have a 50:50 chance of needing a revision,
      and in those older than 62 years the prosthesis will normally outlast the
      patient. Patients over 77 years old have a greater than 90% chance of dying than
      requiring a revision whereas those around 47 years are on average twice as likely
      to require a revision than die. This information can be used to rationalise the
      need for long-term surveillance and during the informed consent process.

PMID- 21969445
TI  - Slipped capital femoral epiphysis: rising rates with obesity and aboriginality in
      South Australia.
AB  - We analysed the incidence of slipped capital femoral epiphysis (SCFE) in South
      Australia, investigating possible associations between an increased incidence of
      SCFE, the local indigenous population and the Australian obesity epidemic during
      the last 20 years. Data including race, age and gender were collected to obtain a
      profile of the South Australian SCFE patient, and were then compared with
      epidemiological data for South Australian adolescents. We concluded that the
      incidence of both obesity and SCFE is increasing. We also noted that the median
      weight of SCFE patients has increased and the mean age at diagnosis has
      decreased. Despite weight profiles comparable with those of the general
      population, we noted that an indigenous child was three times more likely to
      develop SCFE than a non-indigenous child. As far as we know there is no published
      literature on the predisposition of Aboriginal Australians to SCFE.

PMID- 21969446
TI  - Arteriovenous fistula formation after a closed proximal tibial fracture in a
      child.
AB  - Arteriovenous fistula formation after a closed extremity fracture is rare. We
      present the case of an 11-year-old boy who developed an arteriovenous fistula
      between the anterior tibial artery and popliteal vein after closed fractures of
      the proximal tibia and fibula. The fractures were treated by closed reduction and
      casting. A fistula was diagnosed 12 weeks after the injury. It was treated by
      embolisation with coils. Subsequent angiography and ultrasonography confirmed
      patency of the popliteal vein and anterior and posterior tibial and peroneal
      arteries, with no residual shunting through the fistula. The fractures healed
      uneventfully and he returned to full unrestricted activities 21 weeks after his
      injury.

PMID- 21969447
TI  - Adverse reaction to metal release from a modular metal-on-polyethylene hip
      prosthesis.
AB  - A 70-year-old man with an uncemented metal-on-polyethylene total hip prosthesis
      underwent revision arthroplasty 33 months later because of pain, swelling and
      recurrent dislocation. There appeared to be corrosion and metal release from the
      prosthetic head, resulting in pseudotumour formation and severe local soft-tissue
      destruction. The corrosion occurred at the junction between the titanium
      molybdenum-zirconium-iron taper and the cobalt-chrome-molybdenum head, but the
      mechanism was unproven.

PMID- 21969448
TI  - Mechanisms of cramp contractions: peripheral or central generation?
AB  - We analysed the cramp threshold (i.e. the minimum frequency of electrical
      stimulation capable of inducing a cramp) and the behaviour of individual motor
      units during cramps electrically elicited in the absence (intact condition) and
      presence (blocked condition) of a peripheral nerve block in eight healthy
      subjects. The cramp threshold was significantly greater in the blocked than in
      the intact condition (18 +/- 3 Hz vs. 13 +/- 3 Hz; P = 0.01). Cramp duration and
      peak EMG amplitude in the intact condition (55.6 +/- 19.2 s and 47.5 +/- 24.8
      MUV, respectively) were significantly greater compared to the blocked condition
      (2.6 +/- 1.3 s and 13.9 +/- 8.8 MUV; P < 0.01). All motor units identified in the
      blocked condition (n = 38) had a shorter interval of activity and a greater
      discharge rate compared to the intact condition (n = 37) (respectively, 1.1 +/-
      1.0 s vs. 29.5 +/- 21.8 s, P < 0.0001; 25.7 +/- 11.6 pulses s(-1) vs. 20.0 +/-
      5.9 pulses s(-1); P < 0.05). The motor unit activity detected during the blocked
      condition corresponded to spontaneous discharges of the motor nerves, while in
      the intact condition the motor unit discharge patterns presented the typical
      characteristics of motor neuron discharges. These results indicate a spinal
      involvement at the origin of cramps and during their development.

PMID- 21969449
TI  - Reactive oxygen species inactivate neuronal nicotinic acetylcholine receptors
      through a highly conserved cysteine near the intracellular mouth of the channel:
      implications for diseases that involve oxidative stress.
AB  - An intriguing feature of several nicotinic acetylcholine receptors (nAChRs) on
      neurons is that their subunits contain a highly conserved cysteine residue
      located near the intracellular mouth of the receptor pore. The work summarized in
      this review indicates that alpha3beta4-containing and alpha4beta2-containing
      neuronal nAChRs, and possibly other subtypes, are inactivated by elevations in
      intracellular reactive oxygen species (ROS). This review discusses a model for
      the molecular mechanisms that underlie this inactivation. In addition, we explore
      the implications of this mechanism in the context of complications that arise
      from diabetes. We review the evidence that diabetes elevates cytosolic ROS in
      sympathetic neurons and inactivates postsynaptic alpha3beta4-containing nAChRs
      shortly after the onset of diabetes, leading to a depression of synaptic
      transmission in sympathetic ganglia, an impairment of sympathetic reflexes. These
      effects of ROS on nAChR function are due to the highly conserved Cys residues in
      the receptors: replacing the cysteine residues in alpha3 allow ganglionic
      transmission and sympathetic reflexes to function normally in diabetes. This
      example from diabetes suggests that other diseases involving oxidative stress,
      such as Parkinson's disease, could lead to the inactivation of nAChRs on neurons
      and disrupt cholinergic nicotinic signalling.

PMID- 21969450
TI  - A prospective randomised longitudinal MRI study of left ventricular adaptation to
      endurance and resistance exercise training in humans.
AB  - The principle that 'concentric' cardiac hypertrophy occurs in response to
      strength training, whilst 'eccentric' hypertrophy results from endurance exercise
      has been a fundamental tenet of exercise science. This notion is largely based on
      cross-sectional comparisons of athletes using echocardiography. In this study,
      young (27.4 +/- 1.1 years) untrained subjects were randomly assigned to
      supervised, intensive, endurance (END, n = 10) or resistance (RES, n = 13)
      exercise and cardiac MRI scans and myocardial speckle tracking echocardiography
      were performed at baseline, after 6 months of training and after a subsequent 6
      weeks of detraining. Aerobic fitness increased significantly in END (3.5 to 3.8 l
      min(-1), P < 0.05) but was unchanged in RES. Muscular strength significantly
      improved compared to baseline in both RES and END ( = 53.0 +/- 1.1 versus 36.4 +/
      4.5 kg, both P < 0.001) as did lean body mass (2.3 +/- 0.4 kg, P < 0.001 versus
      1.4 +/- 0.6 kg P < 0.05). MRI derived left ventricular (LV) mass increased
      significantly following END (112.5 +/- 7.3 to 121.8 +/- 6.6 g, P < 0.01) but not
      RES, whilst training increased end-diastolic volume (LVEDV, END: +9.0 +/- 5.0
      versus RES +3.1 +/- 3.6 ml, P = 0.05). Interventricular wall thickness
      significantly increased with training in END (1.06 +/- 0.0 to 1.14 +/- 0.06, P <
      0.05) but not RES. Longitudinal strain and strain rates did not change following
      exercise training. Detraining reduced aerobic fitness, LV mass and wall thickness
      in END (P < 0.05), whereas LVEDV remained elevated. This study is the first to
      use MRI to compare LV adaptation in response to intensive supervised endurance
      and resistance training. Our findings provide some support for the 'Morganroth
      hypothesis', as it pertains to LV remodelling in response to endurance training,
      but cast some doubt over the proposal that remodelling occurs in response to
      resistance training.

PMID- 21969451
TI  - Twelve weeks of treadmill exercise does not alter age-dependent chronic kidney
      disease in the Fisher 344 male rat.
AB  - The ageing kidney exhibits slowly developing chronic kidney disease (CKD) and is
      associated with nitric oxide (NO) deficiency and increased oxidative stress. The
      impact of exercise on the ageing kidney is not well understood. Here, we
      determined whether 12 weeks of treadmill exercise can influence age-dependent CKD
      in old (22-24 months) Fisher 344 (F344) male rats by comparing sedentary (SED)
      and exercise (EX) trained rats; young (3 months) rats were also studied. In
      addition to renal structure and function, we assessed protein levels of various
      isoforms of the NO synthases (NOS) and superoxide dismutase (SOD) enzymes as well
      as markers of oxidative stress, in kidney cortex and medulla. Renal function as
      determined by plasma creatinine, proteinuria, and glomerular structural injury
      worsened with age and was unaffected by exercise. Ageing also increased the
      protein abundance of neuronal NOSbeta and p22phox while decreasing extracellular
      (EC) and copper/zinc (CuZn) SOD, in kidney cortex and medulla. H(2)O(2) content
      and nitrotyrosine abundance also increased in the kidney with age. None of these
      age-related changes were altered with exercise. However, exercise did increase
      renal cortical endothelial (e)NOS and EC SOD in young rats. Data indicate that
      exercise-induced increases in eNOS and EC SOD seen in young rats are lost with
      age. We conclude that chronic exercise is ineffective in reversing age-dependent
      CKD in the male F344 rat.

PMID- 21969452
TI  - Effect of muscle metaboreflex activation on spontaneous cardiac baroreflex
      sensitivity during exercise in humans.
AB  - We sought to determine whether the activation of metabolically sensitive skeletal
      muscle afferents (muscle metaboreflex) is a potential mechanism for the decrease
      in spontaneous cardiac baroreflex sensitivity (cBRS) during exercise in humans.
      In protocol 1, 15 male subjects (22 +/- 1 years) performed steady-state leg
      cycling at low (26 +/- 4 W) and moderate workloads (105 +/- 7 W), under free-flow
      conditions and with partial flow restriction (bilateral thigh cuff inflation at
      100 mmHg) to evoke muscle metaboreflex activation during exercise. In protocol 2,
      rhythmic handgrip exercise at 35% maximum voluntary contraction was performed
      with progressive upper arm cuff inflation (0, 80, 100 and 120 mmHg) to elicit
      graded metaboreflex activation. Both protocols were followed by post-exercise
      ischaemia (PEI) to isolate the muscle metaboreflex. Leg cycling-induced increases
      in HR and mean BP were augmented by partial flow restriction (P < 0.05 vs. free
      flow), while HR and mean BP both remained elevated during PEI (P < 0.05 vs.
      rest). Leg cycling evoked an intensity-dependent decrease in cBRS (16 +/- 2, 7 +/
      1 and 2 +/- 0.2 ms mmHg(-1) at rest, low and moderate workloads, respectively; P
      < 0.05), which was further reduced with partial flow restriction (by -2.6 +/- 0.8
      and -0.4 +/- 0.1 ms mmHg(-1) at low and moderate workloads). cBRS remained
      suppressed during PEI following leg cycling with partial flow restriction (4 +/-
      1 ms mmHg(-1); P < 0.05 vs. rest). cBRS was unchanged during handgrip under free
      flow conditions, handgrip with partial flow restriction and PEI following
      handgrip (P > 0.05 vs. rest). These data indicate that the activation of
      metabolically sensitive skeletal muscle afferents (muscle metaboreflex) decreases
      cardiac baroreflex responsiveness during leg cycling exercise in humans.

PMID- 21969453
TI  - Transmembrane AMPA receptor regulatory protein regulation of competitive
      antagonism: a problem of interpretation.
AB  - Synaptic AMPA receptors are greatly influenced by a family of transmembrane AMPA
      receptor regulatory proteins (TARPs) which control trafficking, channel gating
      and pharmacology. The prototypical TARP, stargazin (or gamma2), shifts the
      blocking ability of several AMPAR-selective compounds including the commonly used
      quinoxalinedione antagonists, CNQX and NBQX. Stargazin's effect on CNQX is
      particularly intriguing as it not only apparently lowers the potency of block, as
      with NBQX, but also renders it a partial agonist. Given this, agonist behaviour
      by CNQX has been speculated to account for its weaker blocking effect on AMPAR
      TARP complexes. Here we show that this is not the case. The apparent effect of
      stargazin on CNQX antagonism can be almost entirely explained by an increase in
      the apparent affinity for l-glutamate (l-Glu), a full agonist and
      neurotransmitter at AMPAR synapses. Partial agonism at best plays a minor role
      but not through channel gating per se but rather because CNQX elicits AMPAR
      desensitization. Our study reveals that CNQX is best thought of as a non
      competitive antagonist at glutamatergic synapses due to the predominance of non
      equilibrium conditions. Consequently, CNQX primarily reports the proportion of
      AMPARs available for activation but may also impose additional block by receptor
      desensitization.

PMID- 21969456
TI  - Art and images in psychiatry. Australian rock art: the Giant Wallaroo site.

PMID- 21969454
TI  - Defects in Ca2+ release associated with local expression of pathological
      ryanodine receptors in mouse muscle fibres.
AB  - Mutations of the gene encoding the type 1 ryanodine receptor (RyR1) are
      associated with skeletal muscle disorders including malignant hyperthermia
      susceptibility (MHS) and central core disease (CCD). We used in vivo expression
      of EGFP-RyR1 constructs in fully differentiated mouse muscle fibres to
      characterize the function of several RyR1 mutants. Wild-type and Y523S, R615C,
      R2163H and I4897T mutants of RyR1 were separately expressed and found to be
      present within restricted regions of fibres with a pattern consistent with
      triadic localization. Confocal measurements of voltage-clamp-activated myoplasmic
      Ca(2+) transients demonstrated alterations of sarcoplasmic reticulum (SR) Ca(2+)
      release spatially correlated with the presence of exogenous RyR1s. The Y523S,
      R615C and R2163H RyR1 MHS-related mutants were associated with enhanced peak
      Ca(2+) release for low and moderate levels of depolarization, whereas the I4897T
      CCD mutant produced a chronic reduction of peak SR Ca(2+) release. For example,
      peak Ca(2+) release in response to a depolarization to -20 mV in regions of
      fibres expressing Y523S and I4897T was 2.0 +/- 0.3 (n = 9) and 0.46 +/- 0.1 (n =
      5) times the corresponding value in adjacent, non-expressing regions of the same
      fibre, respectively. Interestingly no significant change in the estimated total
      amount of Ca(2+) released at the end of large depolarizing pulses was observed
      for any of the mutant RyR1 channels. Overall, results are consistent with an
      'inherent' increase in RyR1 sensitivity to activation by the voltage sensor for
      the MHS-related RyR1 mutants and a partial failure of voltage-gated release for
      the CCD-related I4897T mutant, that occur with no sign of change in SR Ca(2+)
      content. Furthermore, the results indicate that RyR1 channel density is tightly
      regulated even under the present conditions of forced exogenous expression.

PMID- 21969455
TI  - Distinct roles for I(T) and I(H) in controlling the frequency and timing of
      rebound spike responses.
AB  - The ability for neurons to generate rebound bursts following inhibitory synaptic
      input relies on ion channels that respond in a unique fashion to
      hyperpolarization. Inward currents provided by T-type calcium channels (I(T)) and
      hyperpolarization-activated HCN channels (I(H)) increase in availability upon
      hyperpolarization, allowing for a rebound depolarization after a period of
      inhibition. Although rebound responses have long been recognized in deep
      cerebellar nuclear (DCN) neurons, the actual extent to which I(T) and I(H)
      contribute to rebound spike output following physiological levels of membrane
      hyperpolarization has not been clearly established. The current study used
      recordings and simulations of large diameter cells of the in vitro rat DCN slice
      preparation to define the roles for I(T) and I(H) in a rebound response. We find
      that physiological levels of hyperpolarization make only small proportions of the
      total I(T) and I(H) available, but that these are sufficient to make substantial
      contributions to a rebound response. At least 50% of the early phase of the
      rebound spike frequency increase is generated by an I(T)-mediated depolarization.
      An additional frequency increase is provided by I(H) in reducing the time
      constant and thus the extent of I(T) inactivation as the membrane returns from a
      hyperpolarized state to the resting level. An I(H)-mediated depolarization
      creates an inverse voltage-first spike latency relationship and produces a 35%
      increase in the precision of the first spike latency of a rebound. I(T) and I(H)
      can thus be activated by physiologically relevant stimuli and have distinct roles
      in the frequency, timing and precision of rebound responses.

PMID- 21969457
TI  - Troubled Sleep, troubled minds, and DSM-5.

PMID- 21969458
TI  - New dimensions in the quantitative classification of mental illness.
AB  - CONTEXT: Patterns of comorbidity among mental disorders are thought to reflect
      the natural organization of mental illness. Factor analysis can be used to
      investigate this structure and construct a quantitative classification system.
      Prior studies identified 3 dimensions of psychopathology: internalizing,
      externalizing, and thought disorder. However, research has largely relied on
      common disorders and community samples. Consequently, it is unclear how well the
      identified organization applies to patients and how other major disorders fit
      into it. OBJECTIVE: To analyze comorbidity among a wide range of Axis I disorders
      and personality disorders (PDs) in the general outpatient population. DESIGN:
      Clinical cohort study. SETTING: A general outpatient practice, the Rhode Island
      Methods to Improve Diagnostic Assessment and Services (MIDAS) project.
      PARTICIPANTS: Outpatients (N = 2900) seeking psychiatric treatment. MAIN OUTCOME
      MEASURES: The Structured Clinical Interview for DSM-IV and the Structured
      Interview for DSM-IV Personality. RESULTS: We tested several alternative
      groupings of the 25 target disorders. The DSM-IV organization fit the data
      poorly. The best-fitting model consisted of 5 factors: internalizing (anxiety and
      eating disorders, major depressive episode, and cluster C, borderline, and
      paranoid PDs), externalizing (substance use disorders and antisocial PD), thought
      disorder (psychosis, mania, and cluster A PDs), somatoform (somatoform
      disorders), and antagonism (cluster B and paranoid PDs). CONCLUSIONS: We
      confirmed the validity of the 3 previously found spectra in an outpatient
      population. We also found novel somatoform and antagonism dimensions, which this
      investigation was able to detect because, to our knowledge, this is the first
      study to include a variety of somatoform and personality disorders. The findings
      suggest that many PDs can be placed in Axis I with related clinical disorders.
      They also suggest that unipolar depression may be better placed with anxiety
      disorders than with bipolar disorders. The emerging quantitative nosology
      promises to provide a more useful guide to clinicians and researchers.

PMID- 21969459
TI  - A high-risk study of bipolar disorder. Childhood clinical phenotypes as
      precursors of major mood disorders.
AB  - CONTEXT: The childhood precursors of adult bipolar disorder (BP) are still a
      matter of controversy. OBJECTIVE: To report the lifetime prevalence and early
      clinical predictors of psychiatric disorders in offspring from families of
      probands with DSM-IV BP compared with offspring of control subjects. DESIGN: A
      longitudinal, prospective study of individuals at risk for BP and related
      disorders. We report initial (cross-sectional and retrospective) diagnostic and
      clinical characteristics following best-estimate procedures. SETTING: Assessment
      was performed at 4 university medical centers in the United States between June
      1, 2006, and September 30, 2009. PARTICIPANTS: Offspring aged 12 to 21 years in
      families with a proband with BP (n = 141, designated as cases) and similarly aged
      offspring of control parents (n = 91). MAIN OUTCOME MEASURE: Lifetime DSM-IV
      diagnosis of a major affective disorder (BP type I; schizoaffective disorder,
      bipolar type; BP type II; or major depression). RESULTS: At a mean age of 17
      years, cases showed a 23.4% lifetime prevalence of major affective disorders
      compared with 4.4% in controls (P = .002, adjusting for age, sex, ethnicity, and
      correlation between siblings). The prevalence of BP in cases was 8.5% vs 0% in
      controls (adjusted P = .007). No significant difference was seen in the
      prevalence of other affective, anxiety, disruptive behavior, or substance use
      disorders. Among case subjects manifesting major affective disorders (n = 33),
      there was an increased risk of anxiety and externalizing disorders compared with
      cases without mood disorder. In cases but not controls, a childhood diagnosis of
      an anxiety disorder (relative risk = 2.6; 95% CI, 1.1-6.3; P = .04) or an
      externalizing disorder (3.6; 1.4-9.0; P = .007) was predictive of later onset of
      major affective disorders. CONCLUSIONS: Childhood anxiety and externalizing
      diagnoses predict major affective illness in adolescent offspring in families
      with probands with BP.

PMID- 21969460
TI  - Early generalized overgrowth in boys with autism.
AB  - CONTEXT: Multiple studies have reported an overgrowth in head circumference (HC)
      in the first year of life in autism. However, it is unclear whether this
      phenomenon is independent of overall body growth and whether it is associated
      with specific social or cognitive features. OBJECTIVES: To examine the trajectory
      of early HC growth in autism compared with control groups; to assess whether HC
      growth in autism is independent of height and weight growth during infancy; and
      to examine HC growth from birth to 24 months in relationship to social, verbal,
      cognitive, and adaptive functioning levels. DESIGN: Retrospective study. SETTING:
      A specialized university-based clinic. PARTICIPANTS: Boys diagnosed as having
      autistic disorder (n = 64), pervasive developmental disorder-not otherwise
      specified (n = 34), global developmental delay (n = 13), and other developmental
      problems (n = 18) and typically developing boys (n = 55). MAIN OUTCOME MEASURES:
      Age-related changes in HC, height, and weight between birth and age 24 months;
      measures of social, verbal, and cognitive functioning at age 2 years. RESULTS:
      Compared with typically developing controls, boys with autism were significantly
      longer by age 4.8 months, had a larger HC by age 9.5 months, and weighed more by
      age 11.4 months (P = .05 for all). None of the other clinical groups showed a
      similar overgrowth pattern. Boys with autism who were in the top 10% of overall
      physical size in infancy exhibited greater severity of social deficits (P = .009)
      and lower adaptive functioning (P = .03). CONCLUSIONS: Boys with autism
      experienced accelerated HC growth in the first year of life. However, this
      phenomenon reflected a generalized process affecting other morphologic features,
      including height and weight. The study highlights the importance of studying
      factors that influence not only neuronal development but also skeletal growth in
      autism.

PMID- 21969461
TI  - Association of maternal and paternal IQ with offspring conduct, emotional, and
      attention problem scores. Transgenerational evidence from the 1958 British Birth
      Cohort Study.
AB  - CONTEXT: Individuals with lower IQ scores have an increased risk of psychological
      disorders, mental health problems, and suicide; similarly, children with low IQ
      scores are more likely to have behavioral, emotional, and anxiety disorders.
      However, little is known about the effect of parental IQ on the mental health
      outcomes of their children. OBJECTIVE: To determine whether maternal and paternal
      IQ scores are associated with offspring conduct, emotional, and attention scores.
      DESIGN: Cohort study. SETTING: General population. PARTICIPANTS: Members of the
      1958 National Child Development Study and their offspring were studied. Of 2984
      parent-offspring pairs with nonadopted children 4 years or older, 2202 pairs had
      complete data regarding all variables of interest and were included in the
      analyses. MAIN OUTCOME MEASURES: Offspring conduct, emotional, and attention
      scores based on the Behavioral Problems Index for children aged 4 to 6 years or
      the Rutter A scale for children and adolescents 7 years and older. RESULTS:
      Little evidence was observed of any association of parental IQ with conduct or
      emotional problems in children aged 4 to 6 years. However, among children and
      adolescents 7 years or older, strong evidence was observed from age- and sex
      adjusted models to support a decrease in conduct, emotional, and attention
      problems in those whose parents had higher IQ scores. These associations were
      linear across the full IQ range. Individual adjustments for socioeconomic status
      and the child's own IQ had limited effect. However, adjustments for Home
      Observation for Measurement of the Environment scores and parental malaise
      attenuated associations with the mother's IQ but had little effect on
      associations with the father's IQ (scores were available for only 1 parent for
      each child or adolescent). Strong associations were no longer evident in models
      that simultaneously adjusted for all 4 potential mediating variables.
      CONCLUSIONS: Children whose parents score poorly on IQ tests may have an
      increased risk of conduct, emotional, and attention problems. The home
      environment, parental malaise, and the child's own IQ may have a role in
      explaining these associations.

PMID- 21969462
TI  - Absolute risk of suicide after first hospital contact in mental disorder.
AB  - CONTEXT: Estimates of lifetime risk of suicide in mental disorders were based on
      selected samples with incomplete follow-up. OBJECTIVE: To estimate, in a national
      cohort, the absolute risk of suicide within 36 years after the first psychiatric
      contact. DESIGN: Prospective study of incident cases followed up for as long as
      36 years. Median follow-up was 18 years. SETTING: Individual data drawn from
      Danish longitudinal registers. PARTICIPANTS: A total of 176,347 persons born from
      January 1, 1955, through December 31, 1991, were followed up from their first
      contact with secondary mental health services after 15 years of age until death,
      emigration, disappearance, or the end of 2006. For each participant, 5 matched
      control individuals were included. MAIN OUTCOME MEASURES: Absolute risk of
      suicide in percentage of individuals up to 36 years after the first contact.
      RESULTS: Among men, the absolute risk of suicide (95% confidence interval [CI])
      was highest for bipolar disorder, (7.77%; 6.01%-10.05%), followed by unipolar
      affective disorder (6.67%; 5.72%-7.78%) and schizophrenia (6.55%; 5.85%-7.34%).
      Among women, the highest risk was found among women with schizophrenia (4.91%;
      95% CI, 4.03%-5.98%), followed by bipolar disorder (4.78%; 3.48%-6.56%). In the
      nonpsychiatric population, the risk was 0.72% (95% CI, 0.61%-0.86%) for men and
      0.26% (0.20%-0.35%) for women. Comorbid substance abuse and comorbid unipolar
      affective disorder significantly increased the risk. The co-occurrence of
      deliberate self-harm increased the risk approximately 2-fold. Men with bipolar
      disorder and deliberate self-harm had the highest risk (17.08%; 95% CI, 11.19%
      26.07%). CONCLUSIONS: This is the first analysis of the absolute risk of suicide
      in a total national cohort of individuals followed up from the first psychiatric
      contact, and it represents, to our knowledge, the hitherto largest sample with
      the longest and most complete follow-up. Our estimates are lower than those most
      often cited, but they are still substantial and indicate the continuous need for
      prevention of suicide among people with mental disorders.

PMID- 21969463
TI  - Importance of anonymity to encourage honest reporting in mental health screening
      after combat deployment.
AB  - CONTEXT: US soldiers are required to undergo screening for depression,
      posttraumatic stress disorder (PTSD), and other mental health problems on return
      from service in Iraq or Afghanistan as part of routine postdeployment health
      assessments. OBJECTIVE: To assess the influence of the anonymity of screening
      processes on willingness of soldiers to report mental health problems after
      combat deployment. DESIGN: Anonymous and nonanonymous surveys. SETTING: US
      military. PATIENTS: US infantry soldiers' reporting of mental health problems on
      the routine Post-Deployment Health Assessment was compared with their reporting
      on an anonymous survey administered simultaneously. MAIN OUTCOME MEASURES: The
      Primary Care PTSD Screen, the Patient Health Questionnaire-2 (modified), the
      suicidal ideation question from the Patient Health Questionnaire-9, and several
      other questions related to mental health were used on both surveys. Soldiers were
      also asked on the anonymous survey about perceptions of stigma and willingness to
      report honestly. RESULTS: Of 3502 US Army soldiers from one infantry brigade
      combat team undergoing the routine Post-Deployment Health Assessment in 2008, a
      total of 2500 were invited to complete the anonymous survey, and 1712 of these
      participated (response rate, 68.5%). Reporting of depression, PTSD, suicidal
      ideation, and interest in receiving care were 2-fold to 4-fold higher on the
      anonymous survey compared with the routine Post-Deployment Health Assessment.
      Overall, 20.3% of soldiers who screened positive for depression or PTSD reported
      that they were uncomfortable reporting their answers honestly on the routine
      postdeployment screening. CONCLUSIONS: Current postdeployment mental health
      screening tools are dependent on soldiers honestly reporting their symptoms. This
      study indicates that the Post-Deployment Health Assessment screening process
      misses most soldiers with significant mental health problems. Further efforts are
      required to reduce the stigma of reporting and improve willingness to receive
      care for mental health problems.

PMID- 21969464
TI  - Long-term outcomes of disability benefits in US veterans with posttraumatic
      stress disorder.
AB  - CONTEXT: Most studies examining the clinical impact of disability benefits have
      compared aid recipients with people who never applied for benefits. Such
      practices may bias findings against recipients because disability applicants tend
      to be much sicker than never-applicants. Furthermore, these studies ignore the
      outcomes of denied claimants. OBJECTIVE: To examine long-term outcomes associated
      with receiving or not receiving Department of Veterans Affairs (VA) disability
      benefits for posttraumatic stress disorder (PTSD), the most common mental
      disorder for which veterans seek such benefits. DESIGN: Comparison of outcomes
      between successful and unsuccessful applicants for VA disability payments.
      Because we could not randomize the receipt of benefits, we used exact matching by
      propensity scores to control for potential baseline differences. We examined
      clinical outcomes approximately 10 years later. SETTING AND PARTICIPANTS:
      Stratified, nationally representative cohort of 3337 veterans who applied for VA
      PTSD disability benefits between January 1, 1994, and December 31, 1998. MAIN
      OUTCOME MEASURES: Assessment on validated survey measures of PTSD; work, role,
      social, and physical functioning; employment; and poverty. We compared outcomes
      with earlier scores. Homelessness and mortality were assessed using
      administrative data. RESULTS: Of still-living cohort members, 85.1% returned
      usable surveys. Symptoms of PTSD were elevated in both groups. After adjustment,
      awardees had more severe PTSD symptoms than denied claimants but were nonetheless
      more likely to have had a meaningful symptom reduction since their last
      assessment (-6.1 vs -4.4; SE, 0.1; P = .01). Both groups had meaningful
      improvements of similar magnitude in work, role, and social functioning (-0.15 vs
      -0.19; SE, 0.01; P = .94), but functioning remained poor nonetheless. Comparing
      awardees with denied claimants after adjustment, 13.2% vs 19.0% were employed (P
      = .11); 15.2% vs 44.8% reported poverty (P < .001); 12.0% vs 20.0% had been
      homeless (P = .02); and 10.4% vs 9.7% had died (P = .66). CONCLUSIONS: Regardless
      of claim outcome, veterans who apply for PTSD disability benefits are highly
      impaired. However, receiving PTSD benefits was associated with clinically
      meaningful reductions in PTSD symptoms and less poverty and homelessness.

PMID- 21969465
TI  - Howard Chang: gene regulation in time and space. Interview by Ben Short.

PMID- 21969467
TI  - Interaction between FIP5 and SNX18 regulates epithelial lumen formation.
AB  - During the morphogenesis of the epithelial lumen, apical proteins are thought to
      be transported via endocytic compartments to the site of the forming lumen,
      although the machinery mediating this transport remains to be elucidated. Rab11
      GTPase and its binding protein, FIP5, are important regulators of polarized
      endocytic transport. In this study, we identify sorting nexin 18 as a novel FIP5
      interacting protein and characterize the role of FIP5 and SNX18 in epithelial
      lumen morphogenesis. We show that FIP5 mediates the transport of apical proteins
      from apical endosomes to the apical plasma membrane and, along with SNX18, is
      required for the early stages of apical lumen formation. Furthermore, both
      proteins bind lipids, and FIP5 promotes the capacity of SNX18 to tubulate
      membranes, which implies a role for FIP5 and SNX18 in endocytic carrier formation
      and/or scission. In summary, the present findings support the hypothesis that
      this FIP5-SNX18 complex plays a pivotal role in the polarized transport of apical
      proteins during apical lumen initiation in epithelial cells.

PMID- 21969466
TI  - Pathogens and polymers: microbe-host interactions illuminate the cytoskeleton.
AB  - Intracellular pathogens subvert the host cell cytoskeleton to promote their own
      survival, replication, and dissemination. Study of these microbes has led to many
      discoveries about host cell biology, including the identification of cytoskeletal
      proteins, regulatory pathways, and mechanisms of cytoskeletal function. Actin is
      a common target of bacterial pathogens, but recent work also highlights the use
      of microtubules, cytoskeletal motors, intermediate filaments, and septins. The
      study of pathogen interactions with the cytoskeleton has illuminated key cellular
      processes such as phagocytosis, macropinocytosis, membrane trafficking, motility,
      autophagy, and signal transduction.

PMID- 21969468
TI  - TPX2 regulates the localization and activity of Eg5 in the mammalian mitotic
      spindle.
AB  - Mitotic spindle assembly requires the regulated activity of numerous spindle
      associated proteins. In mammalian cells, the Kinesin-5 motor Eg5 interacts with
      the spindle assembly factor TPX2, but how this interaction contributes to spindle
      formation and function is not established. Using bacterial artificial chromosome
      technology, we generated cells expressing TPX2 lacking the Eg5 interaction
      domain. Spindles in these cells were highly disorganized with multiple spindle
      poles. The TPX2-Eg5 interaction was required for kinetochore fiber formation and
      contributed to Eg5 localization to spindle microtubules but not spindle poles.
      Microinjection of the Eg5-binding domain of TPX2 resulted in spindle elongation,
      indicating that the interaction of Eg5 with TPX2 reduces motor activity.
      Consistent with this possibility, we found that TPX2 reduced the velocity of Eg5
      dependent microtubule gliding, inhibited microtubule sliding, and resulted in the
      accumulation of motor on microtubules. These results establish a novel function
      of TPX2 in regulating the location and activity of the mitotic motor Eg5.

PMID- 21969469
TI  - Molecular networks linked by Moesin drive remodeling of the cell cortex during
      mitosis.
AB  - The cortical mechanisms that drive the series of mitotic cell shape
      transformations remain elusive. In this paper, we identify two novel networks
      that collectively control the dynamic reorganization of the mitotic cortex. We
      demonstrate that Moesin, an actin/membrane linker, integrates these two networks
      to synergize the cortical forces that drive mitotic cell shape transformations.
      We find that the Pp1-87B phosphatase restricts high Moesin activity to early
      mitosis and down-regulates Moesin at the polar cortex, after anaphase onset.
      Overactivation of Moesin at the polar cortex impairs cell elongation and thus
      cytokinesis, whereas a transient recruitment of Moesin is required to retract
      polar blebs that allow cortical relaxation and dissipation of intracellular
      pressure. This fine balance of Moesin activity is further adjusted by Skittles
      and Pten, two enzymes that locally produce phosphoinositol 4,5-bisphosphate and
      thereby, regulate Moesin cortical association. These complementary pathways
      provide a spatiotemporal framework to explain how the cell cortex is remodeled
      throughout cell division.

PMID- 21969470
TI  - FAK is required for the assembly of podosome rosettes.
AB  - Podosomes are dynamic actin-enriched membrane structures that play an important
      role in invasive cell motility and extracellular matrix degradation. They are
      often found to assemble into large rosettelike structures in highly invasive
      cells. However, the mechanism of this assembly remains obscure. In this study, we
      identified focal adhesion kinase (FAK) as a key molecule necessary for assembly.
      Moreover, phosphorylation of p130Cas and suppression of Rho signaling by FAK were
      found to be important for FAK to induce the assembly of podosome rosettes.
      Finally, we found that suppression of vimentin intermediate filaments by FAK
      facilitates the assembly of podosome rosettes. Collectively, our results strongly
      suggest a link between FAK, podosome rosettes, and tumor invasion and unveil a
      negative role for Rho signaling and vimentin filaments in podosome rosette
      assembly.

PMID- 21969472
TI  - A riot of divergent thinking.

PMID- 21969471
TI  - Knowledge sharing and collaboration in translational research, and the DC-THERA
      Directory.
AB  - Biomedical research relies increasingly on large collections of data sets and
      knowledge whose generation, representation and analysis often require large
      collaborative and interdisciplinary efforts. This dimension of 'big data'
      research calls for the development of computational tools to manage such a vast
      amount of data, as well as tools that can improve communication and access to
      information from collaborating researchers and from the wider community. Whenever
      research projects have a defined temporal scope, an additional issue of data
      management arises, namely how the knowledge generated within the project can be
      made available beyond its boundaries and life-time. DC-THERA is a European
      'Network of Excellence' (NoE) that spawned a very large collaborative and
      interdisciplinary research community, focusing on the development of novel
      immunotherapies derived from fundamental research in dendritic cell
      immunobiology. In this article we introduce the DC-THERA Directory, which is an
      information system designed to support knowledge management for this research
      community and beyond. We present how the use of metadata and Semantic Web
      technologies can effectively help to organize the knowledge generated by modern
      collaborative research, how these technologies can enable effective data
      management solutions during and beyond the project lifecycle, and how resources
      such as the DC-THERA Directory fit into the larger context of e-science.

PMID- 21969473
TI  - What is it with kids these days?

PMID- 21969474
TI  - Re: clinical leadership and management in the NHS.

PMID- 21969475
TI  - Research assessment - still opera in theatres.

PMID- 21969476
TI  - Can generalism help revive the primary healthcare vision?

PMID- 21969477
TI  - Reducing global health inequalities. Part 2: myriad challenges.

PMID- 21969478
TI  - Data re-entry overload: time for a paradigm shift in maternity IT?
AB  - This paper provides an overview of maternity information technology (IT) in
      Britain, questioning the usability, effectiveness and cost efficiency of the
      current models of implementation of electronic maternity records. UK experience
      of hand-held paper obstetric notes and computerized records reveals fundamental
      problems in the relationship between the two complementary methods of recording
      maternity data. The assumption that paper records would inevitably be replaced by
      electronic substitutes has proven false; the rigidity of analysable electronic
      records has led to immense incompatibility problems. The flexibility of paper
      records has distinct advantages that have so far not been sufficiently
      acknowledged. It is suggested that continuing work is needed to encourage the
      standardization of electronic maternity records, via a new co-creative, co
      development approach and continuing international electronic community debate.

PMID- 21969479
TI  - Use of outcomes in monitoring healthcare - how many outcome measures are needed
      in monitoring diabetes in primary care?
AB  - OBJECTIVES: To investigate the relationship between patient experience assessed
      through surveys of random samples of practice populations and intermediate
      outcome targets in those patients with diabetes, collected in the Quality and
      Outcomes Framework pay-for-performance scheme. DESIGN: Cross-sectional study.
      SETTING: The East Midlands region of England. PARTICIPANTS: Six hundred and
      twenty-nine general practices. MAIN OUTCOME MEASURES: Logistic regression models
      were used to assess whether practice-level reports of patient experience of
      access and consultations were associated with achievement of treatment targets
      (HbA1c of 7.5% and 10% or lower, BP 145/85 mmHg or lower, and cholesterol 5
      mmol/L or lower) in people with diabetes. Survey respondent characteristics
      (ethnicity, age, sex) and practice size, deprivation, and prevalence of diabetes
      and obesity were also assessed within the models. RESULTS: Patient experience of
      practice populations explained little of the variation in diabetes treatment
      targets. In the practice survey, the proportion of respondents who had seen a
      nurse in the last 6 months was associated with increased likelihood of achieving
      HbA1c of 7.5%, and being involved in decision-making or having tests and
      treatment explained were associated with achievement of HbA1c of 10% or less,
      cholesterol of 5 mmol/L or less, and BP of 145/85 or less. CONCLUSIONS: Although
      patient experience at practice level should be included in monitoring outcomes,
      it should not replace monitoring clinical outcomes in diabetes. A mix of clinical
      and patient experience measures will have to be used to monitor outcomes in
      general practice.

PMID- 21969480
TI  - Extraluminal bowel obstruction by endometrioid adenocarcinoma 34 years post
      hysterectomy: risks of unopposed oestrogen therapy.

PMID- 21969481
TI  - Donald Darnley Reid (1914-1977).

PMID- 21969482
TI  - My working day: Andrew Vallance-Owen.

PMID- 21969485
TI  - Remembering Dr. Wilder Penfield.

PMID- 21969486
TI  - Remembering Dr. Wilder Penfield.

PMID- 21969487
TI  - Recommendations for stroke: 2010.

PMID- 21969488
TI  - Measurement of family health teams is underdeveloped.

PMID- 21969490
TI  - Context fear learning specifically activates distinct populations of neurons in
      amygdala and hypothalamus.
AB  - The identity and distribution of neurons that are involved in any learning or
      memory event is not known. In previous studies, we identified a discrete
      population of neurons in the lateral amygdala that show learning-specific
      activation of a c-fos-regulated transgene following context fear conditioning.
      Here, we have extended these studies to look throughout the amygdala for learning
      specific activation. We identified two further neuronal populations, in the
      amygdalo-striatal transition area and medial amygdala, that show learning
      specific activation. We also identified a population of hypothalamic neurons that
      show strong learning-specific activation. In addition, we asked whether these
      neurons are activated following recall of fear-conditioning memory. None of the
      populations of neurons we identified showed significant memory-recall-related
      activation. These findings suggest that a series of discrete populations of
      neurons are involved in fear learning in amygdala and hypothalamus. The lack of
      reactivation during memory recall suggests that these neurons either do not
      undergo substantial change following recall, or that c-fos is not involved in any
      such activation and change.

PMID- 21969491
TI  - No child left behind in SDHB testing for paragangliomas and pheochromocytomas.

PMID- 21969492
TI  - Effects of low-dose opioids on cognitive dysfunction.

PMID- 21969489
TI  - Neural circuitry and plasticity mechanisms underlying delay eyeblink
      conditioning.
AB  - Pavlovian eyeblink conditioning has been used extensively as a model system for
      examining the neural mechanisms underlying associative learning. Delay eyeblink
      conditioning depends on the intermediate cerebellum ipsilateral to the
      conditioned eye. Evidence favors a two-site plasticity model within the
      cerebellum with long-term depression of parallel fiber synapses on Purkinje cells
      and long-term potentiation of mossy fiber synapses on neurons in the anterior
      interpositus nucleus. Conditioned stimulus and unconditioned stimulus inputs
      arise from the pontine nuclei and inferior olive, respectively, converging in the
      cerebellar cortex and deep nuclei. Projections from subcortical sensory nuclei to
      the pontine nuclei that are necessary for eyeblink conditioning are beginning to
      be identified, and recent studies indicate that there are dynamic interactions
      between sensory thalamic nuclei and the cerebellum during eyeblink conditioning.
      Cerebellar output is projected to the magnocellular red nucleus and then to the
      motor nuclei that generate the blink response(s). Tremendous progress has been
      made toward determining the neural mechanisms of delay eyeblink conditioning but
      there are still significant gaps in our understanding of the necessary neural
      circuitry and plasticity mechanisms underlying cerebellar learning.

PMID- 21969493
TI  - Complete clinical response in squamous cell carcinoma of the rectum with liver
      metastases.

PMID- 21969494
TI  - Impressive response with imatinib in a heavily pretreated patient with metastatic
      c-KIT mutated thymic carcinoma.

PMID- 21969495
TI  - Randomized placebo-controlled phase II trial of perifosine plus capecitabine as
      second- or third-line therapy in patients with metastatic colorectal cancer.
AB  - PURPOSE: In a multicenter, double-blind phase II trial, we compared the efficacy
      and safety of perifosine plus capecitabine (P-CAP) with placebo plus capecitabine
      (CAP) in patients with metastatic colorectal cancer (mCRC) who had progressed
      after as many as two prior therapies. PATIENTS AND METHODS: Patients (n = 38) not
      previously treated with capecitabine received P-CAP (perifosine 50 mg orally once
      daily, days 1 to 21 and CAP 825 mg/m(2) orally twice daily, days 1 to 14) or CAP
      (825 mg/m(2) orally twice daily, days 1 to 14) in 21-day cycles until disease
      progression. The primary end point was time to progression (TTP). Secondary end
      points included overall survival (OS), overall response rate (ORR), safety, and
      tolerability. RESULTS: Twenty patients were randomly assigned to P-CAP and 18 to
      CAP. Median TTP (27.5 v 10.1 weeks; P < .001) and median OS (17.7 v 7.6 months; P
      = .0052) were improved in patients receiving P-CAP versus CAP. ORR was 20% v 7%
      in the P-CAP and CAP groups, respectively, and one patient in the P-CAP group had
      a complete response. A subset analysis of fluorouracil-refractory patients showed
      a median TTP of 17.6 v 9.0 weeks (P < .001) and median OS of 15.1 v 6.5 months (P
      = .0061). Toxicities, including diarrhea, nausea, fatigue, and hand-foot
      syndrome, were manageable. CONCLUSION: P-CAP showed promising clinical activity
      compared with CAP in previously treated patients with mCRC. A phase III trial is
      underway comparing P-CAP with CAP in patients with refractory mCRC.

PMID- 21969496
TI  - Oxaliplatin-induced coronary vasospasm manifesting as Kounis syndrome: a case
      report.

PMID- 21969497
TI  - Metastatic pheochromocytoma/paraganglioma related to primary tumor development in
      childhood or adolescence: significant link to SDHB mutations.
AB  - PURPOSE: To present data on the high rate of SDHB mutations in patients with
      metastatic pheochromocytoma/paraganglioma whose initial tumor presentation began
      in childhood or adolescence. PATIENTS AND METHODS: From 2000 to 2010, 263
      patients with pheochromocytoma/paraganglioma were evaluated through the National
      Institutes of Health (NIH), Bethesda, MD. Of the 263 patients, 125 patients were
      found to have metastatic disease; of these 125 patients, 32 patients presented
      with a tumor before 20 years of age. An additional 17 patients presented with a
      tumor before 20 years of age but demonstrated no development of metastatic
      disease. Genetic testing for mutations in the VHL, MEN, and SDHB/C/D genes was
      performed on patients without previously identified genetic mutations. RESULTS:
      Of the 32 patients who presented with metastatic disease and had their primary
      tumor in childhood or adolescence, sequence analysis of germline DNA showed SDHB
      mutations in 23 patients (71.9%), SDHD mutations in three patients (9.4%), VHL
      mutations in two patients (6.3%), and an absence of a known mutation in four
      patients (12.5%). The majority of these 32 patients (78.1%) presented with
      primary tumors in an extra-adrenal location. CONCLUSION: The majority of patients
      with metastatic pheochromocytoma/paraganglioma who presented with a primary tumor
      in childhood/adolescence had primary extra-adrenal tumors and harbored SDHB
      mutations. Except for primary tumors located in the head and neck where SDHD
      genetic testing is advised, we recommend that patients who present with
      metastatic pheochromocytoma/paraganglioma with primary tumor development in
      childhood or adolescence undergo SDHB genetic testing before they undergo testing
      for other gene mutations, unless clinical presentation or family history suggests
      a different mutation.

PMID- 21969498
TI  - Mortality by stage for right- versus left-sided colon cancer: analysis of
      surveillance, epidemiology, and end results--Medicare data.
AB  - PURPOSE: Recent studies have reported increased mortality for right-sided colon
      cancers but had limited adjustment for patient characteristics and conflicting
      results by stage. We examined the relationship between colon cancer location
      (right- v left-side) and 5-year mortality by stage. PATIENTS AND METHODS: We
      identified Medicare beneficiaries from 1992 to 2005 with American Joint
      Commission on Cancer stages I to III primary adenocarcinoma of the colon who
      underwent surgery for curative intent through Surveillance, Epidemiology, and End
      Results (SEER) -Medicare data. Adjusted hazard ratios (HRs) and 95% CIs for
      predictors of all-cause 5-year mortality were obtained by using Cox proportional
      hazards regression. RESULTS: Of 53,801 patients, 67% had right-sided colon
      cancer. Patients with right-sided cancer were more likely to be older, to be
      women, to be diagnosed with a more advanced stage, and to have more poorly
      differentiated tumors. Adjusted Cox regression showed no significant difference
      in mortality between right- and left-sided cancers for all stages combined (HR,
      1.01; 95% CI, 0.98 to 1.04; P = .598) or for stage I cancers (HR, 0.95; 95% CI,
      0.88 to 1.03; P = .211). Stage II right-sided cancers had lower mortality than
      left-sided cancers (HR, 0.92; 95% CI, 0.87 to 0.97; P = .001), and stage III
      right-sided cancers had higher mortality (HR, 1.12; 95% CI, 1.06 to 1.18; P <
      .001). CONCLUSION: When analysis was adjusted for multiple patient, disease,
      comorbidity, and treatment variables, no overall difference in 5-year mortality
      was seen between right- and left-sided colon cancers. However, within stage II
      disease, right-sided cancers had lower mortality; within stage III, right-sided
      cancers had higher mortality.

PMID- 21969499
TI  - Prediction of early death after induction therapy for newly diagnosed acute
      myeloid leukemia with pretreatment risk scores: a novel paradigm for treatment
      assignment.
AB  - PURPOSE: Outcome in acute myeloid leukemia (AML) worsens with age, at least in
      part because of higher treatment-related mortality (TRM) in older patients.
      Eligibility for intensive AML treatment protocols is therefore typically based on
      age as the implied principal predictor of TRM, although other health- and disease
      related factors modulate this age effect. PATIENTS AND METHODS: We empirically
      defined TRM using estimated weekly hazard rates in 3,365 adults of all ages
      administered intensive chemotherapy for newly diagnosed AML. We used the area
      under the receiver operator characteristic curve (AUC) to quantify the relative
      effects of age and other covariates on TRM in a subset of 2,238 patients. In this
      approach, an AUC of 1.0 denotes perfect prediction, whereas an AUC of 0.5 is
      analogous to a coin flip. RESULTS: Regardless of age, risk of death declined once
      4 weeks had elapsed from treatment start, suggesting that patients who die during
      this time comprise a qualitatively distinct group. Performance status (PS) and
      age were the most important individual predictors of TRM (AUCs of 0.75 and 0.65,
      respectively). However, multicomponent models were significantly more accurate in
      predicting TRM (AUC of 0.83) than PS or age alone. Elimination of age from such
      multicomponent models only minimally affected their predictive accuracy (AUC of
      0.82). CONCLUSION: These data suggest that age is primarily a surrogate for other
      covariates, which themselves add significantly to predictive accuracy, thus
      challenging the wisdom of using age as primary or sole basis for assignment of
      intensive, curative intent treatment in AML.

PMID- 21969500
TI  - Prospective molecular marker analyses of EGFR and KRAS from a randomized, placebo
      controlled study of erlotinib maintenance therapy in advanced non-small-cell lung
      cancer.
AB  - PURPOSE: The phase III, randomized, placebo-controlled Sequential Tarceva in
      Unresectable NSCLC (SATURN; BO18192) study found that erlotinib maintenance
      therapy extended progression-free survival (PFS) and overall survival in patients
      with advanced non-small-cell lung cancer (NSCLC) who had nonprogressive disease
      following first-line platinum-doublet chemotherapy. This study included
      prospective analysis of the prognostic and predictive value of several
      biomarkers. PATIENTS AND METHODS: Mandatory diagnostic tumor specimens were
      collected before initiating first-line chemotherapy and were tested for epidermal
      growth factor receptor (EGFR) protein expression by using immunohistochemistry
      (IHC), EGFR gene copy number by using fluorescent in situ hybridization (FISH),
      and EGFR and KRAS mutations by using DNA sequencing. An EGFR CA simple sequence
      repeat in intron 1 (CA-SSR1) polymorphism was evaluated in blood. RESULTS: All
      889 randomly assigned patients provided tumor samples. EGFR IHC, EGFR FISH, KRAS
      mutation, and EGFR CA-SSR1 repeat length status were not predictive for erlotinib
      efficacy. A profound predictive effect on PFS of erlotinib relative to placebo
      was observed in the EGFR mutation-positive subgroup (hazard ratio [HR], 0.10; P <
      .001). Significant PFS benefits were also observed with erlotinib in the wild
      type EGFR subgroup (HR, 0.78; P = .0185). KRAS mutation status was a significant
      negative prognostic factor for PFS. CONCLUSION: This large prospective biomarker
      study found that patients with activating EGFR mutations derive the greatest PFS
      benefit from erlotinib maintenance therapy. No other biomarkers were predictive
      for outcomes with erlotinib, although the study was not powered for clinical
      outcomes in biomarker subgroups other than EGFR IHC-positive [corrected]. KRAS
      mutations were prognostic for reduced PFS. The study demonstrated the feasibility
      of prospective tissue collection for biomarker analyses in NSCLC.

PMID- 21969501
TI  - Alternative end points to evaluate a therapeutic strategy in advanced colorectal
      cancer: evaluation of progression-free survival, duration of disease control, and
      time to failure of strategy--an Aide et Recherche en Cancerologie Digestive Group
      Study.
AB  - PURPOSE: Progression-free survival (PFS) is not an optimal end point to evaluate
      therapeutic strategies in advanced colorectal cancer (ACRC). Therefore, composite
      end points have been proposed to evaluate a chemotherapy strategy when sequential
      treatments are available: duration of disease control (DDC) and time to failure
      of strategy (TFS). The goal of this study was to evaluate these alternative end
      points and their potential surrogacy for overall survival (OS). METHODS: We
      pooled individual patient data from three randomized trials evaluating
      chemotherapy strategy, which accrued 1,042 patients with previously untreated
      ACRC. In these trials, first-line treatment was either oxaliplatin- or irinotecan
      based chemotherapy. Compared with TFS, DDC included neither time interval between
      progression and next sequence of treatment nor time to progression if the best
      result of the next sequence of treatment was progression. RESULTS: There was good
      correlation between DDC and OS (correlation of median: r, 0.62; correlation of
      hazard ratio [HR]: adjusted copula R(2), 0.72) and between TFS and OS
      (correlation of median: r, 0.59; correlation of HR: adjusted copula R(2), 0.67).
      There was no correlation between PFS and OS (correlation of median: r, 0.45;
      correlation of HR: adjusted copula R(2), 0.47). CONCLUSION: DDC and TFS roughly
      achieved the same results. Both are acceptable new end points to evaluate a
      therapeutic strategy in ACRC. Although TFS achieved a pragmatic evaluation of a
      multiline strategy, DDC captured the effect of a specific sequence in a
      therapeutic strategy.

PMID- 21969502
TI  - Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally
      advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial.
AB  - PURPOSE: The purpose of this trial was to evaluate the role of radiation therapy
      with concurrent gemcitabine (GEM) compared with GEM alone in patients with
      localized unresectable pancreatic cancer. PATIENTS AND METHODS: Patients with
      localized unresectable adenocarcinoma of the pancreas were randomly assigned to
      receive GEM alone (at 1,000 mg/m(2)/wk for weeks 1 to 6, followed by 1 week rest,
      then for 3 of 4 weeks) or GEM (600 mg/m(2)/wk for weeks 1 to 5, then 4 weeks
      later 1,000 mg/m(2) for 3 of 4 weeks) plus radiotherapy (starting on day 1, 1.8
      Gy/Fx for total of 50.4 Gy). Measurement of quality of life using the Functional
      Assessment of Cancer Therapy-Hepatobiliary questionnaire was also performed.
      RESULTS: Of 74 patients entered on trial and randomly assigned to receive GEM
      alone (arm A; n = 37) or GEM plus radiation (arm B; n = 34), patients in arm B
      had greater incidence of grades 4 and 5 toxicities (41% v 9%), but grades 3 and 4
      toxicities combined were similar (77% in A v 79% in B). No statistical
      differences were seen in quality of life measurements at 6, 15 to 16, and 36
      weeks. The primary end point was survival, which was 9.2 months (95% CI, 7.9 to
      11.4 months) and 11.1 months (95% CI, 7.6 to 15.5 months) for arms A and B,
      respectively (one-sided P = .017 by stratified log-rank test). CONCLUSION: This
      trial demonstrates improved overall survival with the addition of radiation
      therapy to GEM in patients with localized unresectable pancreatic cancer, with
      acceptable toxicity.

PMID- 21969503
TI  - Human papillomavirus and rising oropharyngeal cancer incidence in the United
      States.
AB  - PURPOSE: Recent increases in incidence and survival of oropharyngeal cancers in
      the United States have been attributed to human papillomavirus (HPV) infection,
      but empirical evidence is lacking. PATIENTS AND METHODS: HPV status was
      determined for all 271 oropharyngeal cancers (1984-2004) collected by the three
      population-based cancer registries in the Surveillance, Epidemiology, and End
      Results (SEER) Residual Tissue Repositories Program by using polymerase chain
      reaction and genotyping (Inno-LiPA), HPV16 viral load, and HPV16 mRNA expression.
      Trends in HPV prevalence across four calendar periods were estimated by using
      logistic regression. Observed HPV prevalence was reweighted to all oropharyngeal
      cancers within the cancer registries to account for nonrandom selection and to
      calculate incidence trends. Survival of HPV-positive and HPV-negative patients
      was compared by using Kaplan-Meier and multivariable Cox regression analyses.
      RESULTS: HPV prevalence in oropharyngeal cancers significantly increased over
      calendar time regardless of HPV detection assay (P trend < .05). For example, HPV
      prevalence by Inno-LiPA increased from 16.3% during 1984 to 1989 to 71.7% during
      2000 to 2004. Median survival was significantly longer for HPV-positive than for
      HPV-negative patients (131 v 20 months; log-rank P < .001; adjusted hazard ratio,
      0.31; 95% CI, 0.21 to 0.46). Survival significantly increased across calendar
      periods for HPV-positive (P = .003) but not for HPV-negative patients (P = .18).
      Population-level incidence of HPV-positive oropharyngeal cancers increased by
      225% (95% CI, 208% to 242%) from 1988 to 2004 (from 0.8 per 100,000 to 2.6 per
      100,000), and incidence for HPV-negative cancers declined by 50% (95% CI, 47% to
      53%; from 2.0 per 100,000 to 1.0 per 100,000). If recent incidence trends
      continue, the annual number of HPV-positive oropharyngeal cancers is expected to
      surpass the annual number of cervical cancers by the year 2020. CONCLUSION:
      Increases in the population-level incidence and survival of oropharyngeal cancers
      in the United States since 1984 are caused by HPV infection.

PMID- 21969504
TI  - Cisplatin, irinotecan, and bevacizumab for untreated extensive-stage small-cell
      lung cancer: CALGB 30306, a phase II study.
AB  - PURPOSE: The efficacy of cisplatin, irinotecan, and bevacizumab was evaluated in
      patients with extensive-stage small-cell lung cancer (ES-SCLC). PATIENTS AND
      METHODS: Patients with ES-SCLC received cisplatin 30 mg/m(2) and irinotecan 65
      mg/m(2) on days 1 and 8 plus bevacizumab 15 mg/kg on day 1 every 21 days for six
      cycles on this phase II study. The primary end point was to differentiate between
      50% and 65% 12-month survival rates. RESULTS: Seventy-two patients were enrolled
      between March 2005 and April 2006; four patients canceled, and four were
      ineligible. Grade 3 or 4 toxicities included neutropenia (25%), all electrolyte
      (23%), diarrhea (16%), thrombocytopenia (10%), fatigue (10%), nausea (10%),
      hypertension (9%), anemia (9%), infection (7%), vascular access thrombosis (2%),
      stroke (2%), and bowel perforation (1%). Three deaths (5%) occurred on therapy as
      a result of pneumonitis (n = 1), stroke (n =1), and heart failure (n = 1).
      Complete response, partial response, and stable disease occurred in three (5%),
      45 (70%), and 11 patients (17%), respectively. Progressive disease occurred in
      one patient (2%). Overall response rate was 75%. Median progression-free survival
      (PFS) was 7.0 months (95% CI, 6.4 to 8.4 months). Median overall survival (OS)
      was 11.6 months (95% CI, 10.5 to 15.1 months). Hypertension >= grade 1 was
      associated with improved OS after adjusting for performance status (PS) and age
      (hazard ratio [HR], 0.55; 95% CI, 0.31 to 0.97; P = .04). Lower vascular
      endothelial growth factor levels correlated with worse PFS after adjusting for
      age and PS (HR, 0.90; 95% CI, 0.83 to 0.99; P = .03). CONCLUSION: PFS and OS
      times were higher compared with US trials in ES-SCLC with the same chemotherapy.
      However, the primary end point of the trial was not met. Hypertension was
      associated with improved survival after adjusting for age and PS.

PMID- 21969505
TI  - Multivariable model for time to first treatment in patients with chronic
      lymphocytic leukemia.
AB  - PURPOSE: The clinical course for patients with chronic lymphocytic leukemia (CLL)
      is diverse; some patients have indolent disease, never needing treatment, whereas
      others have aggressive disease requiring early treatment. We continue to use
      criteria for active disease to initiate therapy. Multivariable analysis was
      performed to identify prognostic factors independently associated with time to
      first treatment for patients with CLL. PATIENTS AND METHODS: Traditional
      laboratory, clinical prognostic, and newer prognostic factors such as fluorescent
      in situ hybridization (FISH), IGHV mutation status, and ZAP-70 expression
      evaluated at first patient visit to MD Anderson Cancer Center were correlated by
      multivariable analysis with time to first treatment. This multivariable model was
      used to develop a nomogram-a weighted tool to calculate 2- and 4-year probability
      of treatment and estimate median time to first treatment. RESULTS: There were 930
      previously untreated patients who had traditional and new prognostic factors
      evaluated; they did not have active CLL requiring initiation of treatment within
      3 months of first visit and were observed for time to first treatment. The
      following were independently associated with shorter time to first treatment:
      three involved lymph node sites, increased size of cervical lymph nodes, presence
      of 17p deletion or 11q deletion by FISH, increased serum lactate dehydrogenase,
      and unmutated IGHV mutation status. CONCLUSION: We developed a multivariable
      model that incorporates traditional and newer prognostic factors to identify
      patients at high risk for progression to treatment. This model may be useful to
      identify patients for early interventional trials.

PMID- 21969506
TI  - Implications of the oropharyngeal cancer epidemic.

PMID- 21969507
TI  - Conditional probability of survival in patients with newly diagnosed
      glioblastoma.
AB  - PURPOSE: The disease outcome for patients with cancer is typically described in
      terms of estimated survival from diagnosis. Conditional probability offers more
      relevant information regarding survival for patients once they have survived for
      some time. We report conditional survival probabilities on the basis of 498
      patients with glioblastoma multiforme receiving radiation and chemotherapy. For 1
      year survivors, we evaluated variables that may inform subsequent survival.
      Motivated by the trend in data, we also evaluated the assumption of constant
      hazard. PATIENTS AND METHODS: Patients enrolled onto seven phase II protocols
      between 1975 and 2007 were included. Conditional survival probabilities and 95%
      CIs were calculated. The Cox proportional hazards model was used to evaluate
      prognostic values of age, Karnofsky performance score (KPS), and prior
      progression 1-year post diagnosis. To assess the constant hazard assumption, we
      used a likelihood-ratio test to compare the Weibull and exponential
      distributions. RESULTS: The probabilities of surviving an additional year given
      survival to 1, 2, 3, and 4 years were 35%, 49%, 69%, and 93%, respectively. For
      patients who survived for 1 year, lower KPS and progression were significantly
      predictive of shorter survival (both P < .001), but age was not (hazard ratio,
      1.22 for a 10-year increase; P = .25). The Weibull distribution fits the data
      significantly better than exponential (P = .02), suggesting nonconstant hazard.
      CONCLUSION: Conditional probabilities provide encouraging information regarding
      life expectancy to survivors of glioblastoma multiforme. Our data also showed
      that the constant hazard assumption may be violated in modern brain tumor trials.
      For single-arm trials, we advise using individual patient data from historical
      data sets for efficacy comparisons.

PMID- 21969508
TI  - Stereotactic brachytherapy with iodine-125 seeds for the treatment of inoperable
      low-grade gliomas in children: long-term outcome.
AB  - PURPOSE: Resection is generally considered the gold standard for treatment of low
      grade (WHO grades I and II) gliomas (LGGs) in childhood. However, approximately
      30% to 50% of these tumors are inoperable because of their localization in highly
      eloquent brain areas. A few reports have suggested stereotactic brachytherapy
      (SBT) with implantation of iodine-125 ((125)I) seeds as a safe and effective
      local treatment alternative. This single-center study provides a summary of the
      long-term outcome after SBT in one of the largest reported patient series.
      PATIENTS AND METHODS: All pediatric patients treated with SBT ((125)I seeds;
      cumulative therapeutic dose 50-65 Gy within 9 months) by our group for LGG with
      follow-up of more than 6 months were included. Clinical and radiologic outcome,
      time to progression, and overall survival were evaluated. Prognostic factors
      (age, sex, Karnofsky performance score, tumor volume, and histology) for survival
      and disease progression were investigated. RESULTS: In all, 147 of 160 pediatric
      patients treated with SBT (from 1982 through 2009) were analyzed in detail.
      Procedure-related mortality was zero, and the 30-day morbidity was transient and
      low (5.4%). Survival rates at 5 and 10 years were 93%, and 82%, respectively,
      with no significant difference between WHO grades I and II tumors (median follow
      up, 67.1 +/- 57.7 months). Twenty-one (14.8%) of 147 patients presented with
      tumor relapse. The remaining 126 patients revealed complete response in 24.6%,
      partial response in 31.0%, and stable disease in 29.6%. Neurologic status
      improved (57.8%) or remained stable (23.0%). None of the evaluated factors had
      significant impact on the study's end points except tumor volume more than 15 mL,
      which caused significantly higher rates of tumor recurrence (P < .05).
      CONCLUSION: We demonstrate that SBT represents a safe, minimally invasive, and
      highly effective local treatment option for pediatric patients with inoperable
      LGG WHO grades I and II.

PMID- 21969509
TI  - Randomized, double-blind, placebo-controlled phase II study of single-agent oral
      talactoferrin in patients with locally advanced or metastatic non-small-cell lung
      cancer that progressed after chemotherapy.
AB  - PURPOSE: To investigate the activity and safety of oral talactoferrin (TLF) in
      patients with stages IIIB to IV non-small-cell lung cancer (NSCLC) for whom one
      or two prior lines of systemic anticancer therapy had failed. PATIENTS AND
      METHODS: Patients (n = 100) were randomly assigned to receive either oral TLF
      (1.5 g in 15 mL phosphate-based buffer) or placebo (15 mL phosphate-based buffer)
      twice per day in addition to supportive care. Oral TLF or placebo was
      administered for a maximum of three 14-week cycles with dosing for 12 consecutive
      weeks followed by 2 weeks off. The primary objective was overall survival (OS) in
      the intent-to-treat (ITT) patient population. Secondary objectives included
      progression-free survival (PFS), disease control rate (DCR), and safety. RESULTS:
      TLF was associated with improvement in OS in the ITT patient population, meeting
      the protocol-specified level of significance of a one-tailed P = .05. Compared
      with the placebo group, median OS increased by 65% in the TLF group (3.7 to 6.1
      months; hazard ratio, 0.68; 90% CI, 0.47 to 0.98; P = .04 with one-tailed log
      rank test). Supportive trends were also observed for PFS and DCR. TLF was well
      tolerated and, generally, there were fewer adverse events (AEs) and grade >= 3
      AEs reported in the TLF arm. AEs were consistent with those expected in late
      stage NSCLC. CONCLUSION: TLF demonstrated an apparent improvement in OS in
      patients with stages IIIB to IV NSCLC for whom one or two prior lines of systemic
      anticancer therapy had failed and was well tolerated. These results should be
      confirmed in a global phase III trial.

PMID- 21969510
TI  - Symptoms adversely impact survival among patients with cancer and unsuspected
      pulmonary embolism.

PMID- 21969511
TI  - Second cancer risk after chemotherapy for Hodgkin's lymphoma: a collaborative
      British cohort study.
AB  - PURPOSE: We investigated the long-term risk of second primary malignancy after
      chemotherapy for Hodgkin's lymphoma (HL) in a much larger cohort than any yet
      published, to our knowledge. PATIENTS AND METHODS: We followed 5,798 patients
      with HL treated with chemotherapy in Britain from 1963 to 2001--of whom 3,432
      also received radiotherapy--to assess second primary malignancy risks compared
      with general population-based expectations. RESULTS: Second malignancies occurred
      in 459 cohort members. Relative risk (RR) of second cancer was raised after
      chemotherapy alone (RR, 2.0; 95% CI, 1.7 to 2.4) but was much lower than after
      combined modalities (RR, 3.9; 95% CI, 3.5 to 4.4). After chemotherapy alone,
      there were significantly raised risks of lung cancer, non-HL, and leukemia, each
      contributing approximately equal absolute excess risk. After combined modalities,
      there were raised risks of these and several other cancers. Second cancer risk
      peaked 5 to 9 years after chemotherapy alone, but it remained raised for 25 years
      and longer after combined modalities. Risk was raised after each common
      chemotherapy regimen except, based on limited numbers and follow-up, adriamycin,
      bleomycin, vinblastine, and dacarbazine. The age and time-course relations of
      lung cancer differed between chemotherapy alone and combined modalities.
      CONCLUSION: Although chemotherapy alone leads to raised risk of second
      malignancy, this risk is lower and affects fewer anatomic sites than that after
      combined modalities, and it is slight if at all after 15 years follow-up. The
      mechanism of lung cancer etiology may differ between chemotherapy and
      radiotherapy.

PMID- 21969512
TI  - Incidence and outcome of male breast cancer: an international population-based
      study.
AB  - PURPOSE: Male breast cancer is a rare disease with an incidence rate less than 1%
      of that of female breast cancer. Given its low incidence, few studies have
      assessed risk and prognosis. METHODS: This population-based study, including
      459,846 women and 2,665 men diagnosed with breast cancer in Denmark, Finland,
      Geneva, Norway, Singapore, and Sweden over the last 40 years, compares trends in
      incidence, relative survival, and relative excess mortality between the sexes.
      RESULTS: World standardized incidence rates of breast cancer were 66.7 per 10(5)
      person-years in women and 0.40 per 10(5) person-years in men. Women were
      diagnosed at a younger median age (61.7 years) than men (69.6 years). Male
      patients had a poorer 5-year relative survival ratio than women (0.72 [95% CI,
      0.70 to 0.75] v 0.78 [95% CI, 0.78 to 0.78], respectively), corresponding to a
      relative excess risk (RER) of 1.27 (95% CI, 1.13 to 1.42). However, after
      adjustment for age and year of diagnosis, stage, and treatment, male patients had
      a significantly better relative survival from breast cancer than female patients
      (RER, 0.78; 95% CI, 0.62 to 0.97). CONCLUSION: Male patients with breast cancer
      have later onset of disease and more advanced disease than female patients. Male
      patients with breast cancer have lower risk of death from breast cancer than
      comparable female patients.

PMID- 21969513
TI  - Fluorosis because of prolonged voriconazole therapy in a teenager with acute
      myelogenous leukemia.

PMID- 21969514
TI  - Locally advanced pancreatic cancer: where should we go from here?

PMID- 21969515
TI  - Maintenance therapy comes of age for non-small-cell lung cancer, but at what
      cost?

PMID- 21969516
TI  - Prognostic value of the stage 4S metastatic pattern and tumor biology in patients
      with metastatic neuroblastoma diagnosed between birth and 18 months of age.
AB  - PURPOSE: Patients with neuroblastoma younger than 12 months of age with a 4S
      pattern of disease (metastases limited to liver, skin, bone marrow) have better
      outcomes than infants with stage 4 disease. The new International Neuroblastoma
      Risk Group (INRG) staging system extends age to 18 months for the 4S pattern. Our
      aim was to determine which prognostic features could be used for optimal risk
      classification among patients younger than 18 months with metastatic disease.
      METHODS: Event-free survival (EFS) and overall survival were analyzed by log-rank
      tests, Cox models, and survival tree regression for 656 infants with stage 4S
      neuroblastoma younger than 12 months of age and 1,019 patients with stage 4
      disease younger than 18 months of age in the INRG database. RESULTS: Unfavorable
      biologic features were more frequent in infants with stage 4 disease than in
      infants with 4S tumors and higher overall in those age 12 to 18 months (although
      not different for stage 4 v 4S pattern). EFS was significantly better for infants
      younger than 12 months with 4S pattern than with stage 4 disease (P < .01) but
      similar for toddlers age 12 to 18 months with stage 4 versus 4S pattern. Among
      717 patients with stage 4S pattern, patients age 12 to 18 months had worse EFS
      than those age younger than 12 months (P < .01). MYCN, 11q, mitosis-karyorrhexis
      index (MKI), ploidy, and lactate dehydrogenase were independently statistically
      significant predictors of EFS and more highly predictive than age or metastatic
      pattern. MYCN, 11q, MKI, histology, and 1p were combined in a survival tree for
      improved risk stratification. CONCLUSION: Tumor biology is more critical than age
      or metastatic pattern for prognosis of patients age younger than 18 months with
      metastatic neuroblastoma and should be considered for risk stratification.

PMID- 21969517
TI  - Gemcitabine plus nab-paclitaxel is an active regimen in patients with advanced
      pancreatic cancer: a phase I/II trial.
AB  - PURPOSE: The trial objectives were to identify the maximum-tolerated dose (MTD)
      of first-line gemcitabine plus nab-paclitaxel in metastatic pancreatic
      adenocarcinoma and to provide efficacy and safety data. Additional objectives
      were to evaluate positron emission tomography (PET) scan response, secreted
      protein acidic and rich in cysteine (SPARC), and CA19-9 levels in relation to
      efficacy. Subsequent preclinical studies investigated the changes involving the
      pancreatic stroma and drug uptake. PATIENTS AND METHODS: Patients with previously
      untreated advanced pancreatic cancer were treated with 100, 125, or 150 mg/m(2)
      nab-paclitaxel followed by gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 every
      28 days. In the preclinical study, mice were implanted with human pancreatic
      cancers and treated with study agents. RESULTS: A total of 20, 44, and three
      patients received nab-paclitaxel at 100, 125, and 150 mg/m(2), respectively. The
      MTD was 1,000 mg/m(2) of gemcitabine plus 125 mg/m(2) of nab-paclitaxel once a
      week for 3 weeks, every 28 days. Dose-limiting toxicities were sepsis and
      neutropenia. At the MTD, the response rate was 48%, with 12.2 median months of
      overall survival (OS) and 48% 1-year survival. Improved OS was observed in
      patients who had a complete metabolic response on [(18)F]fluorodeoxyglucose PET.
      Decreases in CA19-9 levels were correlated with increased response rate,
      progression-free survival, and OS. SPARC in the stroma, but not in the tumor, was
      correlated with improved survival. In mice with human pancreatic cancer
      xenografts, nab-paclitaxel alone and in combination with gemcitabine depleted the
      desmoplastic stroma. The intratumoral concentration of gemcitabine was increased
      by 2.8-fold in mice receiving nab-paclitaxel plus gemcitabine versus those
      receiving gemcitabine alone. CONCLUSION: The regimen of nab-paclitaxel plus
      gemcitabine has tolerable adverse effects with substantial antitumor activity,
      warranting phase III evaluation.

PMID- 21969518
TI  - Human hepatic cytochrome P450-specific metabolism of the organophosphorus
      pesticides methyl parathion and diazinon.
AB  - Organophosphorus pesticides (OPs) are a public health concern due to their
      worldwide use and documented human exposures. Phosphorothioate OPs are
      metabolized by cytochrome P450s (P450s) through either a dearylation reaction to
      form an inactive metabolite, or through a desulfuration reaction to form an
      active oxon metabolite, which is a potent cholinesterase inhibitor. This study
      investigated the rate of desulfuration (activation) and dearylation
      (detoxification) of methyl parathion and diazinon in human liver microsomes. In
      addition, recombinant human P450s were used to determine the P450-specific
      kinetic parameters (K(m) and V(max)) for each compound for future use in refining
      human physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) models of
      OP exposure. The primary enzymes involved in bioactivation of methyl parathion
      were CYP2B6 (K(m) = 1.25 MUM; V(max) = 9.78 nmol . min(-1) . nmol P450(-1)),
      CYP2C19 (K(m) = 1.03 MUM; V(max) = 4.67 nmol . min(-1) . nmol P450(-1)), and
      CYP1A2 (K(m) = 1.96 MUM; V(max) = 5.14 nmol . min(-1) . nmol P450(-1)), and the
      bioactivation of diazinon was mediated primarily by CYP1A1 (K(m) = 3.05 MUM;
      V(max) = 2.35 nmol . min(-1) . nmol P450(-1)), CYP2C19 (K(m) = 7.74 MUM; V(max) =
      4.14 nmol . min(-1) . nmol P450(-1)), and CYP2B6 (K(m) = 14.83 MUM; V(max) = 5.44
      nmol . min(-1) . nmol P450(-1)). P450-mediated detoxification of methyl parathion
      only occurred to a limited extent with CYP1A2 (K(m) = 16.8 MUM; V(max) = 1.38
      nmol . min(-1) . nmol P450(-1)) and 3A4 (K(m) = 104 MUM; V(max) = 5.15 nmol .
      min(-1) . nmol P450(-1)), whereas the major enzyme involved in diazinon
      detoxification was CYP2C19 (K(m) = 5.04 MUM; V(max) = 5.58 nmol . min(-1) . nmol
      P450(-1)). The OP- and P450-specific kinetic values will be helpful for future
      use in refining human PBPK/PD models of OP exposure.

PMID- 21969519
TI  - Effects of chronic renal failure on brain drug transporters in rats.
AB  - Studies demonstrated that chronic renal failure (CRF) affects the expression and
      activity of intestinal, hepatic, and renal drug transporters. Such drug
      transporters are expressed in brain cells and at the blood-brain barrier (BBB),
      where they limit the entry and distribution of drugs in the brain. Perturbations
      in brain drug transporter equilibrium by CRF could lead to central drug toxicity.
      This study evaluates how CRF affects BBB drug transporters using a 5/6
      nephrectomized rat model. Protein and mRNA expression of influx transporters
      [organic anion-transporting polypeptide (Oatp), organic anion transporter (Oat)]
      and efflux transporters [P-glycoprotein (P-gp), multidrug resistance-related
      protein (Mrp), breast cancer resistance protein (Bcrp)] were measured in CRF and
      control rat brain. Intracerebral accumulation of radiolabeled benzylpenicillin,
      digoxin, doxorubicin, and verapamil was used to evaluate BBB drug permeability.
      Protein expression of the transporters was evaluated in rat brain endothelial
      cells (RBECs) and astrocytes incubated with control and CRF rat serum. We
      demonstrated significant decreases (30-50%) in protein and mRNA levels of Bcrp,
      Mrp2 to -4, Oat3, Oatp2 and -3, and P-gp in CRF rat brain biopsies, as well as in
      astrocytes and RBECs incubated with CRF serum. These decreases did not correlate
      with in vivo changes because BBB permeability of benzylpenicillin was decreased
      by 30% in CRF rats, whereas digoxin, doxorubicin, and verapamil permeabilities
      were unchanged. It thus seems that even with decreased drug transporters, BBB
      integrity and function is conserved in CRF.

PMID- 21969520
TI  - Referral to a new psychological therapy service is associated with reduced
      utilisation of healthcare and sickness absence by people with common mental
      health problems: a before and after comparison.
AB  - BACKGROUND: Improving Access to Psychological Therapies (IAPT) is a new programme
      designed to reduce disease burden to the individual and economic burden to the
      society of common mental health problems (CMHP). This is the first study to look
      at the impact of IAPT on health service utilisation and sickness absence using
      routine data. METHOD: The authors used pseudonymised secure and privately linked
      (SAPREL) routinely collected primary, secondary care and clinic computer data
      from two pilot localities. The authors explored antidepressant prescribing,
      accident and emergency and outpatients attendances, inpatient stays, bed days,
      and sick certification. The authors compared the registered population with those
      with CMHP. The authors then made a 6 months before and after comparison of people
      referred to IAPT with age-sex and practice-matched controls. RESULTS: People with
      CMHP used more health resources than those without CMHP: more prescriptions of
      antidepressants 5.25 (95% CI 5.38 to 5.13), inpatient episodes 4.89 (95% CI 5.0
      to 4.79), occupied bed days 1.25 (95% CI 0.95 to 1.55), outpatient 1.5 (95% CI
      1.40 to 1.63) and emergency department attendances 0.34 (95% CI 0.31 to 0.37),
      and medical certificates 0.29 (95% CI 0.26 to 0.32). Comparison of service
      utilisation 6 months before and after referral to IAPT was associated with
      reduced use of emergency department attendances (mean difference: 0.12 (95% CI
      0.06 to 0.19, p<0.001)). However, the number of prescriptions of antidepressants
      increased mean difference -0.15 (95% CI 0.02-0.29, p=0.028). CONCLUSIONS: People
      with CMHP use more healthcare resources. Referral to the IAPT programme is
      associated with a subsequent reduction in emergency department attendances,
      sickness certification and improved adherence to drug treatment.

PMID- 21969521
TI  - The impact of the coronary collateral circulation on mortality: a meta-analysis.
AB  - AIMS: The coronary collateral circulation as an alternative source of blood
      supply has shown benefits regarding several clinical endpoints in patients with
      myocardial infarction (MI) such as infarct size and left ventricular remodelling.
      However, its impact on hard endpoints such as mortality and its impact in
      patients with stable coronary artery disease (CAD) is more controversial. The
      purpose of this systematic review and meta-analysis was to explore the impact of
      collateral circulation on all-cause mortality. METHODS AND RESULTS: We searched
      MEDLINE, EMBASE, ISI Web of Science (2001 to 25 April 2011), and conference
      proceedings for studies evaluating the effect of coronary collaterals on
      mortality. Random-effect models were used to calculate summary risk ratios (RR).
      A total of 12 studies enrolling 6529 participants were included in this analysis.
      Patients with high collateralization showed a reduced mortality compared with
      those with low collateralization [RR 0.64 (95% confidence interval 0.45-0.91); P=
      0.012]. The RR for 'high collateralization' in patients with stable CAD was 0.59
      [0.39-0.89], P= 0.012, in patients with subacute MI it was 0.53 [0.15-1.92]; P=
      0.335, and for patients with acute MI it was 0.63 [0.29-1.39]; P= 0.257.
      CONCLUSIONS: In patients with CAD, the coronary collateralization has a relevant
      protective effect. Patients with a high collateralization have a 36% reduced
      mortality risk compared with patients with low collateralization.

PMID- 21969522
TI  - Assessment of androgen concentration in women: liquid chromatography-tandem mass
      spectrometry and extraction RIA show comparable results.
AB  - OBJECTIVE: The measurement of serum testosterone in women is challenging due to
      lack of trueness, precision, and sensitivity of various available testosterone
      assays. Accurate assessment of testosterone in women is crucial especially in
      conditions associated with alleged over- or under-production of testosterone,
      such as in polycystic ovary syndrome (PCOS) or primary ovarian insufficiency
      (POI). The aim of this study was to measure and compare androgen concentrations
      in women with PCOS, POI, and female controls and to evaluate the performance of
      extraction RIA and liquid chromatography-tandem mass spectrometry (LC-MS/MS) in
      these women. DESIGN: Cross-sectional study. METHODS: Carefully phenotyped women
      with POI (n=208) or PCOS (n=200) and 45 healthy, regularly cyclic female controls
      were included. Method comparison analyses were performed for total testosterone,
      androstenedione (AD), and DHEA, as measured by LC-MS/MS and extraction RIA.
      RESULTS: All androgen levels were significantly elevated in women with PCOS
      compared with POI patients (P<0.05) and controls (P<0.05). Women with POI
      presented with similar androgen concentrations as controls, except for AD.
      Compared with measurements by extraction RIA, testosterone, DHEA, and AD
      concentrations measured by LC-MS/MS were systematically lower. However, using
      extraction RIA and LC-MS/MS, testosterone, DHEA, and AD measurements were shown
      to have good agreement as assessed by Bland-Altman analysis and intraclass
      correlation coefficient: 0.95 (95% confidence interval 0.94-0.91), 0.83 (0.79
      0.86), and 0.96 (0.95-0.97) respectively. CONCLUSIONS: LC-MS/MS, compared with a
      labor-intensive extraction RIA, shows good precision, sensitivity, and high
      accuracy for measuring female testosterone, DHEA, and AD concentrations under
      various clinical conditions. LC-MS/MS, therefore, represents a convenient and
      reliable assay for both clinical and research purposes, where androgen
      measurement in women is required.

PMID- 21969523
TI  - Prevalence and characteristics of the metabolic syndrome in 2479 hypopituitary
      patients with adult-onset GH deficiency before GH replacement: a KIMS analysis.
AB  - OBJECTIVE: An increased risk of cardiovascular morbidity and mortality in adult
      GH deficiency (GHD) may be related to hypopituitarism but also to the presence of
      the metabolic syndrome (MetS). Our objective was to investigate the
      characteristics and prevalence of MetS as well as its comorbidities in adult GHD.
      Design In KIMS (Pfizer International Metabolic Database) 2479 patients with
      severe adult-onset GHD, naive to GH replacement, with complete information on all
      MetS components were found. MetS was defined according to the National
      Cholesterol Education Program's Adult Treatment Panel III (NCEP) and the
      International Diabetes Foundation (IDF). METHODS: The prevalence of MetS was
      calculated and compared with previously published data from the normal
      population. Associations were assessed between background variables, baseline
      variables, comorbidities, and MetS. RESULTS: MetS was present in 43.1% (NCEP) and
      in 49.1% (IDF) of patients, clearly higher than data from the normal population
      (20-30%). MetS prevalence was related to age, GHD duration, and body mass index
      (BMI), but not to GHD severity, extent of hypopituitarism, or etiology of
      pituitary disease. Adjusted for age, gender, and BMI, patients with MetS had a
      higher prevalence ratio for diabetes mellitus: 4.65 (95% confidence interval
      (CI): 3.29-6.58), for cardiovascular morbidity: 1.91 (95% CI: 1.33-2.75), and for
      cerebrovascular morbidity: 1.77 (95% CI: 1.09-2.87) than patients without MetS.
      CONCLUSIONS: MetS is highly prevalent in GHD and is associated with a higher
      prevalence ratio for comorbidities. The presence of MetS in GHD may therefore
      contribute to the increased risk of cardiovascular morbidity and mortality found
      in these patients.

PMID- 21969524
TI  - Orthopaedic splint treatment can reduce mandibular asymmetry caused by unilateral
      temporomandibular involvement in juvenile idiopathic arthritis.
AB  - Unilateral temporomandibular joint (TMJ) arthritis in juvenile idiopathic
      arthritis (JIA) patients often induces asymmetric dentofacial growth. This study
      evaluates the effects of an orthopaedic functional appliance worn full time to
      reduce asymmetric mandibular growth in JIA patients. Twenty-two JIA patients with
      unilateral TMJ involvement were included in the study (mean age 7.5 years, range:
      3.8-13.8 years). They all received orthopaedic treatment with a functional
      appliance, a so-called distraction splint (mean treatment time 57 months).
      Panoramic tomograms or cone beam-computerized tomograms were taken before and
      within 12 months after treatment cessation. At both time points, the ratio
      between the healthy and the affected side of the mandible was evaluated in terms
      of inter-side differences in condylar height, ramus height, and total vertical
      mandibular height. Orthopaedic functional treatment reduced mandibular
      asymmetries in terms of ramus height and total vertical mandibular height (P <
      0.05). Mandibular growth rates in the affected and the non-affected sides were
      comparable in most patients. Our study finds evidence to support that a
      distraction splint can normalize mandibular vertical growth in the affected side.
      We therefore suggest implementation of distraction splint therapy in the
      treatment of JIA patients with unilateral TMJ arthritis.

PMID- 21969525
TI  - Pre-hospital discharge testing after implantable cardioverter defibrillator
      implantation: a measure of safety or out of date? A retrospective analysis of 975
      patients.
AB  - AIMS: The present study evaluates the relevance and additional safety value of
      pre-hospital discharge (PHD) testing in patients with implantable cardioverter
      defibrillator (ICD) therapy. METHODS: From June 1998 to May 2009, 975 patients
      (830 male, 145 female) with ICD were screened retrospectively for failed PHD and
      analysed for its consequences, risk factors, and patient characteristics after
      successful intra-operative testing in the implantation procedure. RESULTS: Pre
      hospital discharge testing procedure was performed in 809 cases. No serious
      adverse events (e.g. death, persistant ventricular fibrillation or ventricular
      tachycardia, stroke) occurred. The overall incidence of failed PHD was 1.4% (n =
      11). The underlying mechanisms were defibrillation threshold failure in 9/11
      cases and sensing failure in 2/11 cases. CONCLUSIONS: In this study predictors
      for PHD-failure are: (i) cardiomyopathy other than ischaemic or dilative, (ii)
      young age, and (iii) small or very large left ventricular end-diastolic diameter
      ( < 40 or > 65 mm). Particularly, (i) manufacture of device or leads, (ii) lead
      design, (iii) medical treatment, or (iv) gender have no significant influence on
      PHD failure.

PMID- 21969526
TI  - ST-elevation during biventricular pacing.
AB  - Pacemakers devaluate the accuracy of the electrocardiogram (ECG) for the
      diagnosis of myocardial ischaemia. We present the case of a 53-year-old man with
      ischaemic cardiomyopathy and acute chest pain. Besides biventricular pacing, new
      ST-segment elevations were present leading to the diagnosis of myocardial
      infarction. However, no ECG criteria for the diagnosis of myocardial ischaemia in
      biventricular-paced rhythm are available.

PMID- 21969527
TI  - A successful percutaneous retrieval of a fractured pacemaker lead from a
      segmental pulmonary artery.
AB  - A rarely reported complication of pacemaker lead extraction is embolization of
      the pulmonary vasculature by a fragmented lead tip. The tip fractured and
      migrated to the right pulmonary artery during the extraction, and it was
      successfully retrieved percutaneously. Percutaneous retrieval is an important
      treatment option of an embolized fragmented lead tip as it could sometimes lead
      to disastrous complications.

PMID- 21969528
TI  - Language intervention in the classroom: what it looks like.

PMID- 21969529
TI  - The integration of lexical, syntactic, and discourse features in bilingual
      adolescents' writing: an exploratory approach.
AB  - PURPOSE: The purpose of this study was to assess the bilingual writing of
      adolescent English language learners (ELLs) using quantitative tools. Linguistic
      measures were applied to the participants' writing at the lexical, syntactic, and
      discourse levels, with the goal of comparing outcomes at each of these levels
      across languages (Spanish/English) and genres (expository/narrative). METHOD:
      Twenty Spanish-speaking ELLs, ages 11-14 years, each produced 8 expository and
      narrative autobiographical texts. Texts were coded and scored for lexical
      sophistication, syntactic complexity, and overall text quality. Scores were
      analyzed using Friedman's 2-way analysis of variance by ranks (Siegel &
      Castellan, 1988); resulting ranks were compared across languages and genre
      topics. RESULTS: The text topic impacted rank differences at all levels.
      Performance at the three levels was similar across languages, indicating that
      participants were emerging writers in both Spanish and English. The impact of
      genre was generally inconsequential at all levels. CONCLUSION: Similar results
      across languages implied the potential transfer of writing skills. Overall,
      students appeared to apply a knowledge-telling strategy to writing rather than
      strategically planning, composing, and revising their writing. Finally, outcomes
      highlighted the synergistic relationships among linguistic levels in text
      composition, indicating a need to address the interaction of vocabulary,
      morphosyntax, and text-level structures in the instruction and assessment of ELL
      writing.

PMID- 21969530
TI  - Grammatical morphology in school-age children with and without language
      impairment: a discriminant function analysis.
AB  - PURPOSE: The purpose of this study was to test Bedore and Leonard's (1998)
      proposal that a verb morpheme composite may hold promise as a clinical marker for
      specific language impairment (SLI) in English speakers and serve as an accurate
      basis for the classification of children with and without SLI beyond the
      preschool level. METHOD: The language transcripts of 50 school-age children with
      SLI (M(age) = 7;9 [years;months]) and 50 age-matched typically developing peers
      (M(age) = 7;9) were analyzed. Following the Bedore and Leonard (1998) procedure,
      3 variables were measured: a finite verb morpheme composite, a noun morpheme
      composite, and mean length of utterance in morphemes (MLU(m)). RESULTS: Overall
      findings indicated that neither grammatical morpheme composite alone adequately
      discriminated the groups at this developmental level. However, combining the verb
      and noun grammatical morpheme composite measures with MLU(m) resulted in good
      discriminant accuracy in classifying subgroups of the youngest children with and
      without SLI in the school-age sample. CONCLUSION: Verb morphology alone is not a
      useful clinical marker of SLI in school-age children. Potential explanations for
      these findings and ideas for future research are discussed.

PMID- 21969531
TI  - Narrative ability of children with speech sound disorders and the prediction of
      later literacy skills.
AB  - PURPOSE: The main purpose of this study was to examine how children with isolated
      speech sound disorders (SSDs; n = 20), children with combined SSDs and language
      impairment (LI; n = 20), and typically developing children (n = 20), ages 3;3
      (years;months) to 6;6, differ in narrative ability. The second purpose was to
      determine if early narrative ability predicts school-age (8-12 years) literacy
      skills. METHOD: This study employed a longitudinal cohort design. The children
      completed a narrative retelling task before their formal literacy instruction
      began. The narratives were analyzed and compared for group differences.
      Performance on these early narratives was then used to predict the children's
      reading decoding, reading comprehension, and written language ability at school
      age. RESULTS: Significant group differences were found in children's (a) ability
      to answer questions about the story, (b) use of story grammars, and (c) number of
      correct and irrelevant utterances. Regression analysis demonstrated that measures
      of story structure and accuracy were the best predictors of the decoding of real
      words, reading comprehension, and written language. Measures of syntax and
      lexical diversity were the best predictors of the decoding of nonsense words.
      CONCLUSION: Combined SSDs and LI, and not isolated SSDs, impact a child's
      narrative abilities. Narrative retelling is a useful task for predicting which
      children may be at risk for later literacy problems.

PMID- 21969532
TI  - Ultrahigh resolution protein structures using NMR chemical shift tensors.
AB  - NMR chemical shift tensors (CSTs) in proteins, as well as their orientations,
      represent an important new restraint class for protein structure refinement and
      determination. Here, we present the first determination of both CST magnitudes
      and orientations for (13)Calpha and (15)N (peptide backbone) groups in a protein,
      the beta1 IgG binding domain of protein G from Streptococcus spp., GB1. Site
      specific (13)Calpha and (15)N CSTs were measured using synchronously evolved
      recoupling experiments in which (13)C and (15)N tensors were projected onto the
      (1)H-(13)C and (1)H-(15)N vectors, respectively, and onto the (15)N-(13)C vector
      in the case of (13)Calpha. The orientations of the (13)Calpha CSTs to the (1)H
      (13)C and (13)C-(15)N vectors agreed well with the results of ab initio
      calculations, with an rmsd of approximately 8 degrees . In addition, the measured
      (15)N tensors exhibited larger reduced anisotropies in alpha-helical versus beta
      sheet regions, with very limited variation (18 +/- 4 degrees ) in the orientation
      of the z-axis of the (15)N CST with respect to the (1)H-(15)N vector.
      Incorporation of the (13)Calpha CST restraints into structure calculations, in
      combination with isotropic chemical shifts, transferred echo double resonance
      (13)C-(15)N distances and vector angle restraints, improved the backbone rmsd to
      0.16 A (PDB ID code 2LGI) and is consistent with existing X-ray structures (0.51
      A agreement with PDB ID code 2QMT). These results demonstrate that chemical shift
      tensors have considerable utility in protein structure refinement, with the best
      structures comparable to 1.0-A crystal structures, based upon empirical metrics
      such as Ramachandran geometries and chi(1)/chi(2) distributions, providing solid
      state NMR with a powerful tool for de novo structure determination.

PMID- 21969533
TI  - Translocation of HIV TAT peptide and analogues induced by multiplexed membrane
      and cytoskeletal interactions.
AB  - Cell-penetrating peptides (CPPs), such as the HIV TAT peptide, are able to
      translocate across cellular membranes efficiently. A number of mechanisms, from
      direct entry to various endocytotic mechanisms (both receptor independent and
      receptor dependent), have been observed but how these specific amino acid
      sequences accomplish these effects is unknown. We show how CPP sequences can
      multiplex interactions with the membrane, the actin cytoskeleton, and cell
      surface receptors to facilitate different translocation pathways under different
      conditions. Using "nunchuck" CPPs, we demonstrate that CPPs permeabilize
      membranes by generating topologically active saddle-splay ("negative Gaussian")
      membrane curvature through multidentate hydrogen bonding of lipid head groups.
      This requirement for negative Gaussian curvature constrains but underdetermines
      the amino acid content of CPPs. We observe that in most CPP sequences decreasing
      arginine content is offset by a simultaneous increase in lysine and hydrophobic
      content. Moreover, by densely organizing cationic residues while satisfying the
      above constraint, TAT peptide is able to combine cytoskeletal remodeling activity
      with membrane translocation activity. We show that the TAT peptide can induce
      structural changes reminiscent of macropinocytosis in actin-encapsulated giant
      vesicles without receptors.

PMID- 21969535
TI  - Combining meteorites and missions to explore Mars.
AB  - Laboratory studies of meteorites and robotic exploration of Mars reveal scant
      atmosphere, no evidence of plate tectonics, past evidence for abundant water, and
      a protracted igneous evolution. Despite indirect hints, direct evidence of a
      martian origin came with the discovery of trapped atmospheric gases in one
      meteorite. Since then, the study of martian meteorites and findings from missions
      have been linked. Although the meteorite source locations are unknown, impact
      ejection modeling and spectral mapping of Mars suggest derivation from small
      craters in terrains of Amazonian to Hesperian age. Whereas most martian
      meteorites are young (< 1.3 Ga), the spread of whole rock isotopic compositions
      results from crystallization of a magma ocean > 4.5 Ga and formation of enriched
      and depleted reservoirs. However, the history inferred from martian meteorites
      conflicts with results from recent Mars missions, calling into doubt whether the
      igneous histor y inferred from the meteorites is applicable to Mars as a whole.
      Allan Hills 84001 dates to 4.09 Ga and contains fluid-deposited carbonates.
      Accompanying debate about the mechanism and temperature of origin of the
      carbonates came several features suggestive of past microbial life in the
      carbonates. Although highly disputed, the suggestion spurred interest in
      habitable extreme environments on Earth and throughout the Solar System. A
      flotilla of subsequent spacecraft has redefined Mars from a volcanic planet to a
      hydrologically active planet that may have harbored life. Understanding the
      history and habitability of Mars depends on understanding the coupling of the
      atmosphere, surface, and subsurface. Sample return that brings back direct
      evidence from these diverse reservoirs is essential.

PMID- 21969534
TI  - Mutagenesis of tryptophan199 suggests that hopping is required for MauG-dependent
      tryptophan tryptophylquinone biosynthesis.
AB  - The diheme enzyme MauG catalyzes the posttranslational modification of the
      precursor protein of methylamine dehydrogenase (preMADH) to complete biosynthesis
      of its protein-derived tryptophan tryptophylquinone (TTQ) cofactor. Catalysis
      proceeds through a high valent bis-Fe(IV) redox state and requires long-range
      electron transfer (ET), as the distance between the modified residues of preMADH
      and the nearest heme iron of MauG is 19.4 A. Trp199 of MauG resides at the MauG
      preMADH interface, positioned midway between the residues that are modified and
      the nearest heme. W199F and W199K mutations did not affect the spectroscopic and
      redox properties of MauG, or its ability to stabilize the bis-Fe(IV) state.
      Crystal structures of complexes of W199F/K MauG with preMADH showed no
      significant perturbation of the MauG-preMADH structure or protein interface.
      However, neither MauG variant was able to synthesize TTQ from preMADH. In
      contrast, an ET reaction from diferrous MauG to quinone MADH, which does not
      require the bis-Fe(IV) intermediate, was minimally affected by the W199F/K
      mutations. W199F/K MauGs were able to oxidize quinol MADH to form TTQ, the
      putative final two-electron oxidation of the biosynthetic process, but with
      k(cat)/K(m) values approximately 10% that of wild-type MauG. The differential
      effects of the W199F/K mutations on these three different reactions are explained
      by a critical role for Trp199 in mediating multistep hopping from preMADH to bis
      Fe(IV) MauG during the long-range ET that is required for TTQ biosynthesis.

PMID- 21969536
TI  - Evidence for short-range helical order in the 30-nm chromatin fibers of
      erythrocyte nuclei.
AB  - Chromatin folding in eukaryotes fits the genome into the limited volume of the
      cell nucleus. Formation of higher-order chromatin structures attenuates DNA
      accessibility, thus contributing to the control of essential genome functions
      such as transcription, DNA replication, and repair. The 30-nm fiber is thought to
      be the first hierarchical level of chromatin folding, but the nucleosome
      arrangement in the compact 30-nm fiber was previously unknown. We used
      cryoelectron tomography of vitreous sections to determine the structure of the
      compact, native 30-nm fiber of avian erythrocyte nuclei. The predominant geometry
      of the 30-nm fiber revealed by subtomogram averaging is a left-handed two-start
      helix with approximately 6.5 nucleosomes per 11 nm, in which the nucleosomes are
      juxtaposed face-to-face but are shifted off their superhelical axes with an axial
      translation of approximately 3.4 nm and an azimuthal rotation of approximately 54
      degrees . The nucleosomes produce a checkerboard pattern when observed in the
      direction perpendicular to the fiber axis but are not interdigitated. The
      nucleosome packing within the fibers shows larger center-to-center
      internucleosomal distances than previously anticipated, thus excluding the
      possibility of core-to-core interactions, explaining how transcription and
      regulation factors can access nucleosomes.

PMID- 21969537
TI  - Discovery of the recoverable high-pressure iron oxide Fe4O5.
AB  - Phases of the iron-oxygen binary system are significant to most scientific
      disciplines, directly affecting planetary evolution, life, and technology. Iron
      oxides have unique electronic properties and strongly interact with the
      environment, particularly through redox reactions. The iron-oxygen phase diagram
      therefore has been among the most thoroughly investigated, yet it still holds
      striking findings. Here, we report the discovery of an iron oxide with formula
      Fe(4)O(5), synthesized at high pressure and temperature. The previously
      undescribed phase, stable from 5 to at least 30 GPa, is recoverable to ambient
      conditions. First-principles calculations confirm that the iron oxide here
      described is energetically more stable than FeO + Fe(3)O(4) at pressure greater
      than 10 GPa. The calculated lattice constants, equation of states, and atomic
      coordinates are in excellent agreement with experimental data, confirming the
      synthesis of Fe(4)O(5). Given the conditions of stability and its composition,
      Fe(4)O(5) is a plausible accessory mineral of the Earth's upper mantle. The phase
      has strong ferrimagnetic character comparable to magnetite. The ability to
      synthesize the material at accessible conditions and recover it at ambient
      conditions, along with its physical properties, suggests a potential interest in
      Fe(4)O(5) for technological applications.

PMID- 21969538
TI  - Crystal structure of the octameric pore of staphylococcal gamma-hemolysin reveals
      the beta-barrel pore formation mechanism by two components.
AB  - Staphylococcal gamma-hemolysin is a bicomponent pore-forming toxin composed of
      LukF and Hlg2. These proteins are expressed as water-soluble monomers and then
      assemble into the oligomeric pore form on the target cell. Here, we report the
      crystal structure of the octameric pore form of gamma-hemolysin at 2.5 A
      resolution, which is the first high-resolution structure of a beta-barrel
      transmembrane protein composed of two proteins reported to date. The octameric
      assembly consists of four molecules of LukF and Hlg2 located alternately in a
      circular pattern, which explains the biochemical data accumulated over the past
      two decades. The structure, in combination with the monomeric forms, demonstrates
      the elaborate molecular machinery involved in pore formation by two different
      molecules, in which interprotomer electrostatic interactions using loops
      connecting beta2 and beta3 (loop A: Asp43-Lys48 of LukF and Lys37-Lys43 of Hlg2)
      play pivotal roles as the structural determinants for assembly through unwinding
      of the N-terminal beta-strands (amino-latch) of the adjacent protomer, releasing
      the transmembrane stem domain folded into a beta-sheet in the monomer (prestem),
      and interaction with the adjacent protomer.

PMID- 21969539
TI  - The ePetri dish, an on-chip cell imaging platform based on subpixel perspective
      sweeping microscopy (SPSM).
AB  - We report a chip-scale lensless wide-field-of-view microscopy imaging technique,
      subpixel perspective sweeping microscopy, which can render microscopy images of
      growing or confluent cell cultures autonomously. We demonstrate that this
      technology can be used to build smart Petri dish platforms, termed ePetri, for
      cell culture experiments. This technique leverages the recent broad and cheap
      availability of high performance image sensor chips to provide a low-cost and
      automated microscopy solution. Unlike the two major classes of lensless
      microscopy methods, optofluidic microscopy and digital in-line holography
      microscopy, this new approach is fully capable of working with cell cultures or
      any samples in which cells may be contiguously connected. With our prototype, we
      demonstrate the ability to image samples of area 6 mm * 4 mm at 660-nm
      resolution. As a further demonstration, we showed that the method can be applied
      to image color stained cell culture sample and to image and track cell culture
      growth directly within an incubator. Finally, we showed that this method can
      track embryonic stem cell differentiations over the entire sensor surface. Smart
      Petri dish based on this technology can significantly streamline and improve cell
      culture experiments by cutting down on human labor and contamination risks.

PMID- 21969540
TI  - Double-core-hole spectroscopy for chemical analysis with an intense X-ray
      femtosecond laser.
AB  - Theory predicts that double-core-hole (DCH) spectroscopy can provide a new
      powerful means of differentiating between similar chemical systems with a
      sensitivity not hitherto possible. Although DCH ionization on a single site in
      molecules was recently measured with double- and single-photon absorption, double
      core holes with single vacancies on two different sites, allowing unambiguous
      chemical analysis, have remained elusive. Here we report that direct observation
      of double-core holes with single vacancies on two different sites produced via
      sequential two-photon absorption, using short, intense X-ray pulses from the
      Linac Coherent Light Source free-electron laser and compare it with theoretical
      modeling. The observation of DCH states, which exhibit a unique signature, and
      agreement with theory proves the feasibility of the method. Our findings exploit
      the ultrashort pulse duration of the free-electron laser to eject two core
      electrons on a time scale comparable to that of Auger decay and demonstrate
      possible future X-ray control of physical inner-shell processes.

PMID- 21969541
TI  - Allosteric vs. spontaneous exit-site (E-site) tRNA dissociation early in protein
      synthesis.
AB  - During protein synthesis, deacylated transfer RNAs leave the ribosome via an exit
      (E) site after mRNA translocation. How the ribosome regulates tRNA dissociation
      and whether functional linkages between the aminoacyl (A) and E sites modulate
      the dynamics of protein synthesis have long been debated. Using single molecule
      fluorescence resonance energy transfer experiments, we find that, during early
      cycles of protein elongation, tRNAs are often held in the E site until being
      allosterically released when the next aminoacyl tRNA binds to the A site. This
      process is regulated by the length and sequence of the nascent peptide and by the
      conformational state, detected by tRNA proximity, prior to translocation. In
      later cycles, E-site tRNA dissociates spontaneously. Our results suggest that the
      distribution of pretranslocation tRNA states and posttranslocation pathways are
      correlated within each elongation cycle via communication between distant
      subdomains in the ribosome, but that this correlation between elongation cycle
      intermediates does not persist into succeeding cycles.

PMID- 21969542
TI  - Structure determination of an intercalating ruthenium dipyridophenazine complex
      which kinks DNA by semiintercalation of a tetraazaphenanthrene ligand.
AB  - We describe a crystal structure, at atomic resolution (1.1 A, 100 K), of a
      ruthenium polypyridyl complex bound to duplex DNA, in which one ligand acts as a
      wedge in the minor groove, resulting in the 51 degrees  kinking of the double
      helix. The complex cation Lambda-[Ru(1,4,5,8
      tetraazaphenanthrene)(2)(dipyridophenazine)](2+) crystallizes in a 11 ratio with
      the oligonucleotide d(TCGGCGCCGA) in the presence of barium ions. Each complex
      binds to one duplex by intercalation of the dipyridophenazine ligand and also by
      semiintercalation of one of the orthogonal tetraazaphenanthrene ligands into a
      second symmetrically equivalent duplex. The result is noncovalent cross-linking
      and marked kinking of DNA.

PMID- 21969543
TI  - Carbonates in the Martian meteorite Allan Hills 84001 formed at 18 +/- 4 degrees
      C in a near-surface aqueous environment.
AB  - Despite evidence for liquid water at the surface of Mars during the Noachian
      epoch, the temperature of early aqueous environments has been impossible to
      establish, raising questions of whether the surface of Mars was ever warmer than
      today. We address this problem by determining the precipitation temperature of
      secondary carbonate minerals preserved in the oldest known sample of Mars' crust-
      the approximately 4.1 billion-year-old meteorite Allan Hills 84001 (ALH84001).
      The formation environment of these carbonates, which are constrained to be
      slightly younger than the crystallization age of the rock (i.e., 3.9 to 4.0
      billion years), has been poorly understood, hindering insight into the hydrologic
      and carbon cycles of earliest Mars. Using "clumped" isotope thermometry we find
      that the carbonates in ALH84001 precipitated at a temperature of approximately 18
      degrees C, with water and carbon dioxide derived from the ancient Martian
      atmosphere. Furthermore, covarying carbonate carbon and oxygen isotope ratios are
      constrained to have formed at constant, low temperatures, pointing to deposition
      from a gradually evaporating, subsurface water body--likely a shallow aquifer
      (meters to tens of meters below the surface). Despite the mild temperatures, the
      apparently ephemeral nature of water in this environment leaves open the question
      of its habitability.

PMID- 21969544
TI  - Binding of blood proteins to carbon nanotubes reduces cytotoxicity.
AB  - With the potential wide uses of nanoparticles such as carbon nanotubes in
      biomedical applications, and the growing concerns of nanotoxicity of these
      engineered nanoparticles, the importance of nanoparticle-protein interactions
      cannot be stressed enough. In this study, we use both experimental and
      theoretical approaches, including atomic force microscope images, fluorescence
      spectroscopy, CD, SDS-PAGE, and molecular dynamics simulations, to investigate
      the interactions of single-wall carbon nanotubes (SWCNTs) with human serum
      proteins, and find a competitive binding of these proteins with different
      adsorption capacity and packing modes. The pi-pi stacking interactions between
      SWCNTs and aromatic residues (Trp, Phe, Tyr) are found to play a critical role in
      determining their adsorption capacity. Additional cellular cytotoxicity assays,
      with human acute monocytic leukemia cell line and human umbilical vein
      endothelial cells, reveal that the competitive bindings of blood proteins on the
      SWCNT surface can greatly alter their cellular interaction pathways and result in
      much reduced cytotoxicity for these protein-coated SWCNTs, according to their
      respective adsorption capacity. These findings have shed light toward the design
      of safe carbon nanotube nanomaterials by comprehensive preconsideration of their
      interactions with human serum proteins.

PMID- 21969546
TI  - Thermodynamic basis for the genome to capsid charge relationship in viral
      encapsidation.
AB  - We establish an appropriate thermodynamic framework for determining the optimal
      genome length in electrostatically driven viral encapsidation. Importantly, our
      analysis includes the electrostatic potential due to the Donnan equilibrium,
      which arises from the semipermeable nature of the viral capsid, i.e., permeable
      to small mobile ions but impermeable to charged macromolecules. Because most
      macromolecules in the cellular milieu are negatively charged, the Donnan
      potential provides an additional driving force for genome encapsidation. In
      contrast to previous theoretical studies, we find that the optimal genome length
      is the result of combined effects from the electrostatic interactions of all
      charged species, the excluded volume and, to a very significant degree, the
      Donnan potential. In particular, the Donnan potential is essential for obtaining
      negatively overcharged viruses. The prevalence of overcharged viruses in nature
      may suggest an evolutionary preference for viruses to increase the amount of
      genome packaged by utilizing the Donnan potential (through increases in the
      capsid radius), rather than high charges on the capsid, so that structural
      stability of the capsid is maintained.

PMID- 21969545
TI  - Molecular hijacking of siroheme for the synthesis of heme and d1 heme.
AB  - Modified tetrapyrroles such as chlorophyll, heme, siroheme, vitamin B(12),
      coenzyme F(430), and heme d(1) underpin a wide range of essential biological
      functions in all domains of life, and it is therefore surprising that the
      syntheses of many of these life pigments remain poorly understood. It is known
      that the construction of the central molecular framework of modified
      tetrapyrroles is mediated via a common, core pathway. Herein a further branch of
      the modified tetrapyrrole biosynthesis pathway is described in denitrifying and
      sulfate-reducing bacteria as well as the Archaea. This process entails the
      hijacking of siroheme, the prosthetic group of sulfite and nitrite reductase, and
      its processing into heme and d(1) heme. The initial step in these transformations
      involves the decarboxylation of siroheme to give didecarboxysiroheme. For d(1)
      heme synthesis this intermediate has to undergo the replacement of two propionate
      side chains with oxygen functionalities and the introduction of a double bond
      into a further peripheral side chain. For heme synthesis didecarboxysiroheme is
      converted into Fe-coproporphyrin by oxidative loss of two acetic acid side
      chains. Fe-coproporphyrin is then transformed into heme by the oxidative
      decarboxylation of two propionate side chains. The mechanisms of these reactions
      are discussed and the evolutionary significance of another role for siroheme is
      examined.

PMID- 21969547
TI  - Evidence of denser MgSiO3 glass above 133 gigapascal (GPa) and implications for
      remnants of ultradense silicate melt from a deep magma ocean.
AB  - Ultralow velocity zones are the largest seismic anomalies in the mantle, with 10
      30% seismic velocity reduction observed in thin layers less than 20-40 km thick,
      just above the Earth's core-mantle boundary (CMB). The presence of silicate
      melts, possibly a remnant of a deep magma ocean in the early Earth, have been
      proposed to explain ultralow velocity zones. It is, however, still an open
      question as to whether such silicate melts are gravitationally stable at the
      pressure conditions above the CMB. Fe enrichment is usually invoked to explain
      why melts would remain at the CMB, but this has not been substantiated
      experimentally. Here we report in situ high-pressure acoustic velocity
      measurements that suggest a new transformation to a denser structure of MgSiO(3)
      glass at pressures close to those of the CMB. The result suggests that MgSiO(3)
      melt is likely to become denser than crystalline MgSiO(3) above the CMB. The
      presence of negatively buoyant and gravitationally stable silicate melts at the
      bottom of the mantle, would provide a mechanism for observed ultralow seismic
      velocities above the CMB without enrichment of Fe in the melt. An ultradense melt
      phase and its geochemical inventory would be isolated from overlying convective
      flow over geologic time.

PMID- 21969548
TI  - Redox cycling and kinetic analysis of single molecules of solution-phase nitrite
      reductase.
AB  - Single-molecule measurements are a valuable tool for revealing details of enzyme
      mechanisms by enabling observation of unsynchronized behavior. However, this
      approach often requires immobilizing the enzyme on a substrate, a process which
      may alter enzyme behavior. We apply a microfluidic trapping device to allow, for
      the first time, prolonged solution-phase measurement of single enzymes in
      solution. Individual redox events are observed for single molecules of a blue
      nitrite reductase and are used to extract the microscopic kinetic parameters of
      the proposed catalytic cycle. Changes in parameters as a function of substrate
      concentration are consistent with a random sequential substrate binding
      mechanism.

PMID- 21969549
TI  - Full p53 transcriptional activation potential is dispensable for tumor
      suppression in diverse lineages.
AB  - Over half of all human cancers, of a wide variety of types, sustain mutations in
      the p53 tumor suppressor gene. Although p53 limits tumorigenesis through the
      induction of apoptosis or cell cycle arrest, its molecular mechanism of action in
      tumor suppression has been elusive. The best-characterized p53 activity in vitro
      is as a transcriptional activator, but the identification of numerous additional
      p53 biochemical activities in vitro has made it unclear which mechanism accounts
      for tumor suppression. Here, we assess the importance of transcriptional
      activation for p53 tumor suppression function in vivo in several tissues, using a
      knock-in mouse strain expressing a p53 mutant compromised for transcriptional
      activation, p53(25,26). p53(25,26) is severely impaired for the transactivation
      of numerous classical p53 target genes, including p21, Noxa, and Puma, but it
      retains the ability to activate a small subset of p53 target genes, including
      Bax. Surprisingly, p53(25,26) can nonetheless suppress tumor growth in cancers
      derived from the epithelial, mesenchymal, central nervous system, and lymphoid
      lineages. Therefore, full transactivation of most p53 target genes is dispensable
      for p53 tumor suppressor function in a range of tissue types. In contrast, a
      transcriptional activation mutant that is completely defective for
      transactivation, p53(25,26,53,54), fails to suppress tumor development. These
      findings demonstrate that transcriptional activation is indeed broadly critical
      for p53 tumor suppressor function, although this requirement reflects the limited
      transcriptional activity observed with p53(25,26) rather than robust
      transactivation of a full complement of p53 target genes.

PMID- 21969550
TI  - A complex between contactin-1 and the protein tyrosine phosphatase PTPRZ controls
      the development of oligodendrocyte precursor cells.
AB  - The six members of the contactin (CNTN) family of neural cell adhesion molecules
      are involved in the formation and maintenance of the central nervous system (CNS)
      and have been linked to mental retardation and neuropsychiatric disorders such as
      autism. Five of the six CNTNs bind to the homologous receptor protein tyrosine
      phosphatases gamma (PTPRG) and zeta (PTPRZ), but the biological roles of these
      interactions remain unclear. We report here the cocrystal structure of the
      carbonic anhydrase-like domain of PTPRZ bound to tandem Ig repeats of CNTN1 and
      combine these structural data with binding assays to show that PTPRZ binds
      specifically to CNTN1 expressed at the surface of oligodendrocyte precursor
      cells. Furthermore, analyses of glial cell populations in wild-type and PTPRZ
      deficient mice show that the binding of PTPRZ to CNTN1 expressed at the surface
      of oligodendrocyte precursor cells inhibits their proliferation and promotes
      their development into mature oligodendrocytes. Overall, these results implicate
      the PTPRZ/CNTN1 complex as a previously unknown modulator of oligodendrogenesis.

PMID- 21969551
TI  - Evidence for evolution in response to natural selection in a contemporary human
      population.
AB  - It is often claimed that modern humans have stopped evolving because cultural and
      technological advancements have annihilated natural selection. In contrast,
      recent studies show that selection can be strong in contemporary populations.
      However, detecting a response to selection is particularly challenging; previous
      evidence from wild animals has been criticized for both applying anticonservative
      statistical tests and failing to consider random genetic drift. Here we study
      life-history variation in an insular preindustrial French-Canadian population and
      apply a recently proposed conservative approach to testing microevolutionary
      responses to selection. As reported for other such societies, natural selection
      favored an earlier age at first reproduction (AFR) among women. AFR was also
      highly heritable and genetically correlated to fitness, predicting a
      microevolutionary change toward earlier reproduction. In agreement with this
      prediction, AFR declined from about 26-22 y over a 140-y period. Crucially, we
      uncovered a substantial change in the breeding values for this trait, indicating
      that the change in AFR largely occurred at the genetic level. Moreover, the
      genetic trend was higher than expected under the effect of random genetic drift
      alone. Our results show that microevolution can be detectable over relatively few
      generations in humans and underscore the need for studies of human demography and
      reproductive ecology to consider the role of evolutionary processes.

PMID- 21969553
TI  - Dysbindin-1 mutant mice implicate reduced fast-phasic inhibition as a final
      common disease mechanism in schizophrenia.
AB  - DTNBP1 (dystrobrevin binding protein 1) is a leading candidate susceptibility
      gene in schizophrenia and is associated with working memory capacity in normal
      subjects. In schizophrenia, the encoded protein dystrobrevin-binding protein 1
      (dysbindin-1) is often reduced in excitatory cortical limbic synapses. We found
      that reduced dysbindin-1 in mice yielded deficits in auditory-evoked response
      adaptation, prepulse inhibition of startle, and evoked gamma-activity, similar to
      patterns in schizophrenia. In contrast to the role of dysbindin-1 in
      glutamatergic transmission, gamma-band abnormalities in schizophrenia are most
      often attributed to disrupted inhibition and reductions in parvalbumin-positive
      interneuron (PV cell) activity. To determine the mechanism underlying
      electrophysiological deficits related to reduced dysbindin-1 and the potential
      role of PV cells, we examined PV cell immunoreactivity and measured changes in
      net circuit activity using voltage-sensitive dye imaging. The dominant circuit
      impact of reduced dysbindin-1 was impaired inhibition, and PV cell
      immunoreactivity was reduced. Thus, this model provides a link between a
      validated candidate gene and an auditory endophenotypes. Furthermore, these data
      implicate reduced fast-phasic inhibition as a common underlying mechanism of
      schizophrenia-associated intermediate phenotypes.

PMID- 21969552
TI  - Natural gas and temperature structured a microbial community response to the
      Deepwater Horizon oil spill.
AB  - Microbial communities present in the Gulf of Mexico rapidly responded to the
      Deepwater Horizon oil spill. In deep water plumes, these communities were
      initially dominated by members of Oceanospirillales, Colwellia, and
      Cycloclasticus. None of these groups were abundant in surface oil slick samples,
      and Colwellia was much more abundant in oil-degrading enrichment cultures
      incubated at 4  degrees C than at room temperature, suggesting that the colder
      temperatures at plume depth favored the development of these communities. These
      groups decreased in abundance after the well was capped in July, but the addition
      of hydrocarbons in laboratory incubations of deep waters from the Gulf of Mexico
      stimulated Colwellia's growth. Colwellia was the primary organism that
      incorporated (13)C from ethane and propane in stable isotope probing experiments,
      and given its abundance in environmental samples at the time that ethane and
      propane oxidation rates were high, it is likely that Colwellia was active in
      ethane and propane oxidation in situ. Colwellia also incorporated (13)C benzene,
      and Colwellia's abundance in crude oil enrichments without natural gas suggests
      that it has the ability to consume a wide range of hydrocarbon compounds or their
      degradation products. However, the fact that ethane and propane alone were
      capable of stimulating the growth of Colwellia, and to a lesser extent,
      Oceanospirillales, suggests that high natural gas content of this spill may have
      provided an advantage to these organisms.

PMID- 21969554
TI  - Mycobacterium tuberculosis lipomannan blocks TNF biosynthesis by regulating
      macrophage MAPK-activated protein kinase 2 (MK2) and microRNA miR-125b.
AB  - Contact of Mycobacterium tuberculosis (M.tb) with the immune system requires
      interactions between microbial surface molecules and host pattern recognition
      receptors. Major M.tb-exposed cell envelope molecules, such as lipomannan (LM),
      contain subtle structural variations that affect the nature of the immune
      response. Here we show that LM from virulent M.tb (TB-LM), but not from avirulent
      Myocobacterium smegmatis (SmegLM), is a potent inhibitor of TNF biosynthesis in
      human macrophages. This difference in response is not because of variation in
      Toll-like receptor 2-dependent activation of the signaling kinase MAPK p38.
      Rather, TB-LM stimulation leads to destabilization of TNF mRNA transcripts and
      subsequent failure to produce TNF protein. In contrast, SmegLM enhances MAPK
      activated protein kinase 2 phosphorylation, which is critical for maintaining TNF
      mRNA stability in part by contributing microRNAs (miRNAs). In this context, human
      miRNA miR-125b binds to the 3' UTR region of TNF mRNA and destabilizes the
      transcript, whereas miR-155 enhances TNF production by increasing TNF mRNA half
      life and limiting expression of SHIP1, a negative regulator of the PI3K/Akt
      pathway. We show that macrophages incubated with TB-LM and live M.tb induce high
      miR-125b expression and low miR-155 expression with correspondingly low TNF
      production. In contrast, SmegLM and live M. smegmatis induce high miR-155
      expression and low miR-125b expression with high TNF production. Thus, we
      identify a unique cellular mechanism underlying the ability of a major M.tb cell
      wall component, TB-LM, to block TNF biosynthesis in human macrophages, thereby
      allowing M.tb to subvert host immunity and potentially increase its virulence.

PMID- 21969555
TI  - Distinct patterns of Period gene expression in the suprachiasmatic nucleus
      underlie circadian clock photoentrainment by advances or delays.
AB  - The circadian clock in the mammalian hypothalamic suprachiasmatic nucleus (SCN)
      is entrained by the ambient light/dark cycle, which differentially acts to cause
      the clock to advance or delay. Light-induced changes in the rhythmic expression
      of SCN clock genes are believed to be a critical step in this process, but how
      the two entrainment modalities--advances vs. delays--engage the molecular
      clockwork remains incompletely understood. We investigated molecular substrates
      of photic entrainment of the clock in the SCN by stably entraining hamsters to T
      cycles (non-24-h light/dark cycles) consisting of a single 1-h light pulse
      repeated as either a short (23.33-h) or a long (24.67-h) cycle; under these
      conditions, the light pulse of the short cycle acts as "dawn," whereas that of
      the long cycle acts as "dusk." Analyses of the expression of the photoinducible
      and rhythmic clock genes Period 1 and 2 (Per1 and Per2) in the SCN revealed
      fundamental differences under these two entrainment modes. Light at dawn advanced
      the clock, advancing the onset of the Per1 mRNA rhythm and acutely increasing
      mRNA transcription, whereas light at dusk delayed the clock, delaying the offset
      of the Per2 mRNA rhythm and tonically increasing mRNA stability. The results
      suggest that the underlying molecular mechanisms of circadian entrainment differ
      with morning (advancing) or evening (delaying) light exposure, and such
      differences may reflect how entrainment takes place in nocturnal animals under
      natural conditions.

PMID- 21969556
TI  - Chromatin plasticity and the pathogenesis of Huntington disease.

PMID- 21969557
TI  - Induction of 9-cis-epoxycarotenoid dioxygenase in Arabidopsis thaliana seeds
      enhances seed dormancy.
AB  - Full understanding of mechanisms that control seed dormancy and germination
      remains elusive. Whereas it has been proposed that translational control plays a
      predominant role in germination, other studies suggest the importance of specific
      gene expression patterns in imbibed seeds. Transgenic plants were developed to
      permit conditional expression of a gene encoding 9-cis-epoxycarotenoid
      dioxygenase 6 (NCED6), a rate-limiting enzyme in abscisic acid (ABA)
      biosynthesis, using the ecdysone receptor-based plant gene switch system and the
      ligand methoxyfenozide. Induction of NCED6 during imbibition increased ABA levels
      more than 20-fold and was sufficient to prevent seed germination. Germination
      suppression was prevented by fluridone, an inhibitor of ABA biosynthesis. In
      another study, induction of the NCED6 gene in transgenic seeds of nondormant
      mutants tt3 and tt4 reestablished seed dormancy. Furthermore, inducing expression
      of NCED6 during seed development suppressed vivipary, precocious germination of
      developing seeds. These results indicate that expression of a hormone metabolism
      gene in seeds can be a sole determinant of dormancy. This study opens the
      possibility of developing a robust technology to suppress or promote seed
      germination through engineering pathways of hormone metabolism.

PMID- 21969558
TI  - Induced pluripotency leapfrogs ahead.

PMID- 21969559
TI  - Chronic inflammation promotes myeloid-derived suppressor cell activation blocking
      antitumor immunity in transgenic mouse melanoma model.
AB  - Tumor microenvironment is characterized by chronic inflammation represented by
      infiltrating leukocytes and soluble mediators, which lead to a local and systemic
      immunosuppression associated with cancer progression. Here, we used the ret
      transgenic spontaneous murine melanoma model that mimics human melanoma. Skin
      tumors and metastatic lymph nodes showed increased levels of inflammatory factors
      such as IL-1beta, GM-CSF, and IFN-gamma, which correlated with tumor progression.
      Moreover, Gr1(+)CD11b(+) myeloid-derived suppressor cells (MDSCs), known to
      inhibit tumor reactive T cells, were enriched in melanoma lesions and lymphatic
      organs during tumor progression. MDSC infiltration was associated with a strong
      TCR zeta-chain down-regulation in all T cells. Coculturing normal splenocytes
      with tumor-derived MDSC induced a decreased T-cell proliferation and zeta-chain
      expression, verifying the MDSC immunosuppressive function and suggesting that the
      tumor inflammatory microenvironment supports MDSC recruitment and
      immunosuppressive activity. Indeed, upon manipulation of the melanoma
      microenvironment with the phosphodiesterase-5 inhibitor sildenafil, we observed
      reduced levels of numerous inflammatory mediators (e.g., IL-1beta, IL-6, VEGF,
      S100A9) in association with decreased MDSC amounts and immunosuppressive
      function, indicating an antiinflammatory effect of sildenafil. This led to a
      partial restoration of zeta-chain expression in T cells and to a significantly
      increased survival of tumor-bearing mice. CD8 T-cell depletion resulted in an
      abrogation of sildenafil beneficial outcome, suggesting the involvement of MDSC
      and CD8 T cells in the observed therapeutic effects. Our data imply that
      inhibition of chronic inflammation in the tumor microenvironment should be
      applied in conjunction with melanoma immunotherapies to increase their efficacy.

PMID- 21969560
TI  - Elevated Hedgehog/Gli signaling causes beta-cell dedifferentiation in mice.
AB  - Although Hedgehog (Hh) signaling regulates cell differentiation during pancreas
      organogenesis, the consequences of pathway up-regulation in adult beta-cells in
      vivo have not been investigated. Here, we elevate Hh signaling in beta-cells by
      expressing an active version of the GLI2 transcription factor, a mediator of the
      Hh pathway, in beta-cells that are also devoid of primary cilia, a critical
      regulator of Hh activity. We show that increased Hh signaling leads to impaired
      beta-cell function and insulin secretion, resulting in glucose intolerance in
      transgenic mice. This phenotype was accompanied by reduced expression of both
      genes critical for beta-cell function and transcription factors associated with
      their mature phenotype. Increased Hh signaling further correlated with increased
      expression of the precursor cell markers Hes1 and Sox9, both direct Hh targets
      that are normally excluded from beta-cells. Over time, the majority of beta-cells
      down-regulated GLI2 levels, thereby regaining the full differentiation state and
      restoring normoglycemia in transgenic mice. However, sustained high Hh levels in
      some insulin-producing cells further eroded the beta-cell identity and eventually
      led to the development of undifferentiated pancreatic tumors. Summarily, our
      results indicate that deregulation of the Hh pathway impairs beta-cell function
      by interfering with the mature beta-cell differentiation state.

PMID- 21969561
TI  - The telomeric Cdc13 protein interacts directly with the telomerase subunit Est1
      to bring it to telomeric DNA ends in vitro.
AB  - In Saccharomyces cerevisiae, a Cdc13-Est1 interaction is proposed to mediate
      recruitment of telomerase to DNA ends. Here we provide unique in vitro evidence
      for this model by demonstrating a direct interaction between purified Cdc13 and
      Est1. The Cdc13-Est1 interaction is specific and requires the in vivo defined
      Cdc13 recruitment domain. Moreover, in the absence of this interaction, Est1 is
      excluded from telomeric single-stranded (ss)DNA. The apparent association
      constand (K(d)) between Est1 and a Cdc13-telomeric ssDNA complex was ~250 nM. In
      G2 phase cells, where telomerase is active, Cdc13 and Est1 were sufficiently
      abundant (~420 and ~110 copies per cell, respectively) to support complex
      formation. Interaction between Cdc13 and Est1 was unchanged by three telomerase
      deficient mutations, Cdc13(E252K) (cdc13-2), Est1(K444E) (est1-60), and
      Cdc13(S249,255D), indicating that their telomerase null phenotypes are not due to
      loss of the Cdc13-Est1 interaction. These data recapitulate in vitro the first
      step in telomerase recruitment to telomeric ssDNA and suggest that this step is
      necessary to recruit telomerase to DNA ends.

PMID- 21969562
TI  - Acoustic interference and recognition space within a complex assemblage of
      dendrobatid frogs.
AB  - In species-rich assemblages of acoustically communicating animals, heterospecific
      sounds may constrain not only the evolution of signal traits but also the much
      less-studied signal-processing mechanisms that define the recognition space of a
      signal. To test the hypothesis that the recognition space is optimally designed,
      i.e., that it is narrower toward the species that represent the higher potential
      for acoustic interference, we studied an acoustic assemblage of 10 diurnally
      active frog species. We characterized their calls, estimated pairwise
      correlations in calling activity, and, to model the recognition spaces of five
      species, conducted playback experiments with 577 synthetic signals on 531 males.
      Acoustic co-occurrence was not related to multivariate distance in call
      parameters, suggesting a minor role for spectral or temporal segregation among
      species uttering similar calls. In most cases, the recognition space overlapped
      but was greater than the signal space, indicating that signal-processing traits
      do not act as strictly matched filters against sounds other than homospecific
      calls. Indeed, the range of the recognition space was strongly predicted by the
      acoustic distance to neighboring species in the signal space. Thus, our data
      provide compelling evidence of a role of heterospecific calls in evolutionarily
      shaping the frogs' recognition space within a complex acoustic assemblage without
      obvious concomitant effects on the signal.

PMID- 21969563
TI  - Intestinal inflammation allows Salmonella to use ethanolamine to compete with the
      microbiota.
AB  - Conventional wisdom holds that microbes support their growth in vertebrate hosts
      by exploiting a large variety of nutrients. We show here that use of a specific
      nutrient (ethanolamine) confers a marked growth advantage on Salmonella enterica
      serovar Typhimurium (S. Typhimurium) in the lumen of the inflamed intestine. In
      the anaerobic environment of the gut, ethanolamine supports little or no growth
      by fermentation. However, S. Typhimurium is able to use this carbon source by
      inducing the gut to produce a respiratory electron acceptor (tetrathionate),
      which supports anaerobic growth on ethanolamine. The gut normally converts
      ambient hydrogen sulfide to thiosulfate, which it then oxidizes further to
      tetrathionate during inflammation. Evidence is provided that S. Typhimurium's
      growth advantage in an inflamed gut is because of its ability to respire
      ethanolamine, which is released from host tissue, but is not utilizable by
      competing bacteria. By inducing intestinal inflammation, S. Typhimurium sidesteps
      nutritional competition and gains the ability to use an abundant simple
      substrate, ethanolamine, which is provided by the host.

PMID- 21969564
TI  - Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) integrates
      developmental signals for eyelid closure.
AB  - Developmental eyelid closure is an evolutionarily conserved morphogenetic event
      requiring proliferation, differentiation, cytoskeleton reorganization, and
      migration of epithelial cells at the tip of the developing eyelid. Many signaling
      events take place during eyelid closure, but how the signals converge to regulate
      the morphogenetic process remains an open and intriguing question. Here we show
      that mitogen-activated protein kinase kinase kinase 1 (MAP3K1) highly expressed
      in the developing eyelid epithelium, forms with c-Jun, a regulatory axis that
      orchestrates morphogenesis by integrating two different networks of eyelid
      closure signals. A TGF-alpha/EGFR-RhoA module initiates one of these networks by
      inducing c-Jun expression which, in a phosphorylation-independent manner, binds
      to the Map3k1 promoter and causes an increase in MAP3K1 expression. RhoA knockout
      in the ocular surface epithelium disturbs this network by decreasing MAP3K1
      expression, and causes delayed eyelid closure in Map3k1 hemizygotes. The second
      network is initiated by the enzymatic activity of MAP3K1, which phosphorylates
      and activates a JNK-c-Jun module, leading to AP-1 transactivation and induction
      of its downstream genes, such as Pai-1. MAP3K1 inactivation reduces AP-1 activity
      and PAI-1 expression both in cells and developing eyelids. MAP3K1 is therefore
      the nexus of an intracrine regulatory loop connecting the TGF-alpha/EGFR/RhoA-c
      Jun and JNK-c-Jun-AP-1 pathways in developmental eyelid closure.

PMID- 21969565
TI  - Multimodal neuroimaging dissociates hemodynamic and electrophysiological
      correlates of error processing.
AB  - Recognizing errors and adjusting responses are fundamental to adaptive behavior.
      The error-related negativity (ERN) and error-related functional MRI (fMRI)
      activation of the dorsal anterior cingulate cortex (dACC) index these processes
      and are thought to reflect the same neural mechanism. In the present study, we
      evaluated this hypothesis. Although errors elicited robust dACC activation using
      fMRI, combined electroencephalography and magnetoencephalography data localized
      the ERN to the posterior cingulate cortex (PCC). ERN amplitude correlated with
      fMRI activation in both the PCC and dACC, and these two regions showed
      coordinated activity based on functional connectivity MRI. Finally, increased
      microstructural integrity of the posterior cingulum bundle, as measured by
      diffusion tensor imaging, predicted faster error correction. These findings
      suggest that the PCC generates the ERN and communicates with the dACC to subserve
      error processing. They challenge current models that view fMRI activation of the
      dACC as the hemodynamic reflection of the ERN.

PMID- 21969566
TI  - Yeast pheromone receptor genes STE2 and STE3 are differently regulated at the
      transcription and polyadenylation level.
AB  - The orderly expression of specific genes is the basis for cell differentiation.
      Saccharomyces cerevisiae has two haploid mating types, a and alpha cells, in
      which the mating-specific genes are differentially expressed. When a and alpha
      cells are committed to mate, their growth is arrested. Here we show that a
      cryptic polyadenylation site is present inside the coding region of the a
      specific STE2 gene, encoding the receptor for the alpha-factor. The two cell
      types produce an incomplete STE2 transcript, but only a cells generate full
      length STE2 mRNA. We eliminated the cryptic poly(A) signal, thereby allowing the
      production of a complete STE2 mRNA in alpha cells. We mutagenized alpha cells and
      isolated a mutant producing full-length STE2 mRNA. The mutation occurred in the
      ITC1 gene, whose product, together with the product of ISW2, is known to repress
      STE2 transcriptional initiation. We propose that the regulation of the yeast
      mating genes is achieved through a concerted mechanism involving transcriptional
      and posttranscriptional events. In particular, the early poly(A) site in STE2
      could contribute to a complete shutoff of its expression in alpha cells, avoiding
      autocrine activation and growth arrest. Remarkably, no cryptic poly(A) sites are
      present in the a-factor receptor STE3 gene, indicating that S. cerevisiae has
      devised different strategies to regulate the two receptor genes. It is
      predictable that a correlation between the repression of a gene and the presence
      of a cryptic poly(A) site could also be found in other organisms, especially when
      expression of that gene may be harmful.

PMID- 21969568
TI  - Critical roles of chemokine receptor CCR10 in regulating memory IgA responses in
      intestines.
AB  - Chemokine receptor CCR10 is expressed by all intestinal IgA-producing plasma
      cells and is suggested to play an important role in positioning these cells in
      the lamina propria for proper IgA production to maintain intestinal homeostasis
      and protect against infection. However, interfering with CCR10 or its ligand did
      not impair intestinal IgA production under homeostatic conditions or during
      infection, and the in vivo function of CCR10 in the intestinal IgA response
      remains unknown. We found that an enhanced generation of IgA(+) cells in isolated
      lymphoid follicles of intestines offset defective intestinal migration of IgA(+)
      cells in CCR10-KO mice, resulting in the apparently normal IgA production under
      homeostatic conditions and in primary response to pathogen infection. However,
      the compensatorily generated IgA(+) cells in CCR10-KO mice carried fewer
      hypermutations in their Ig heavy chain alleles than those of WT mice, indicating
      that their IgA repertoires are qualitatively different, which might impact the
      intestinal homeostasis of microflora. In addition, CCR10-deficient long-lived IgA
      producing plasma cells and IgA(+) memory B cells generated against the pathogen
      infection could not be maintained properly in intestines. Consequently, IgA
      memory responses to the pathogen reinfection were severely impaired in CCR10-KO
      mice. These findings elucidate critical roles of CCR10 in regulating the
      intestinal IgA response and memory maintenance and could help in design of
      vaccines against intestinal and possibly other mucosal pathogens.

PMID- 21969567
TI  - A molecular mechanism of direction switching in the flagellar motor of
      Escherichia coli.
AB  - The direction of flagellar rotation is regulated by a rotor-mounted protein
      assembly, termed the "switch complex," formed from multiple copies of the
      proteins FliG, FliM, and FliN. The structures of major parts of these proteins
      are known, and the overall organization of proteins in the complex has been
      elucidated previously using a combination of protein-binding, mutational, and
      cross-linking approaches. In Escherichia coli, the switch from counterclockwise
      to clockwise rotation is triggered by the signaling protein phospho-CheY, which
      binds to the lower part of the switch complex and induces small movements of FliM
      and FliN subunits relative to each other. Direction switching also must produce
      movements in the upper part of the complex, particularly in the C-terminal domain
      of FliG (FliG(C)), which interacts with the stator to generate the torque for
      flagellar rotation. In the present study, protein movements in the middle and
      upper parts of the switch complex have been probed by means of targeted cross
      linking and mutational analysis. Switching induces a tilting movement of the FliM
      domains that form the middle part of the switch and a consequent rotation of the
      affixed FliG(C) domains that reorients the stator interaction sites by about 90
      degrees . In a recently proposed hypothesis for the motor mechanism, such a
      reorientation of FliG(C) would reverse the direction of motor rotation.

PMID- 21969569
TI  - Modulation of canonical Wnt signaling by the extracellular matrix component
      biglycan.
AB  - Although extracellular control of canonical Wnt signaling is crucial for tissue
      homeostasis, the role of the extracellular microenvironment in modulating this
      signaling pathway is largely unknown. In the present study, we show that a member
      of the small leucine-rich proteoglycan family, biglycan, enhances canonical Wnt
      signaling by mediating Wnt function via its core protein. Immunoprecipitation
      analysis revealed that biglycan interacts with both the canonical Wnt ligand
      Wnt3a and the Wnt coreceptor low-density lipoprotein receptor-related protein 6
      (LRP6), possibly via the formation of a trimeric complex. Biglycan-deficient
      cells treated with exogenous Wnt3a had less Wnt3a retained in cell layers
      compared with WT cells. Furthermore, the Wnt-induced levels of LRP6
      phosphorylation and expression of several Wnt target genes were blunted in
      biglycan-deficient cells. Both recombinant biglycan proteoglycan and biglycan
      core protein increased Wnt-induced beta-catenin/T cell-specific factor-mediated
      transcriptional activity, and this activity was completely inhibited by Dickkopf
      1. Interestingly, recombinant biglycan was able to rescue impaired Wnt signaling
      caused by a previously described missense mutation in the extracellular domain of
      human LRP6 (R611C). Furthermore, biglycan's modulation of canonical Wnt signaling
      affected the functional activities of osteoprogenitor cells, including the RUNX2
      mediated transcriptional activity and calcium deposition. Use of a transplant
      system and a fracture healing model revealed that expression of Wnt-induced
      secreted protein 1 was decreased in bone formed by biglycan-deficient cells,
      further suggesting reduced Wnt signaling in vivo. We propose that biglycan may
      serve as a reservoir for Wnt in the pericellular space and modulate Wnt
      availability for activation of the canonical Wnt pathway.

PMID- 21969571
TI  - Societal challenges in understanding and responding to regime shifts in forest
      landscapes.

PMID- 21969570
TI  - Truncated neurokinin-1 receptor is increased in colonic epithelial cells from
      patients with colitis-associated cancer.
AB  - Patients with chronic ulcerative colitis (UC) are at high risk for developing
      colorectal cancer. In this study, archival formalin-fixed paraffin-embedded
      colonic tissue from patients with UC who developed carcinoma (CA) or high-grade
      dysplasia (HGD) was examined for changes in expression of the proinflammatory and
      mitogenic neurokinin-1 receptor (NK-1R). Laser capture microscopy was used to
      microdissect epithelia from areas of colons that showed histologic evidence of
      CA, HGD, and epithelia that were not dysplastic or cancerous but did contain
      evidence of prior inflammation (quiescent colitis). mRNA was extracted from the
      dissected tissue, and PCR array analysis was performed on extracted mRNA. Two
      antibodies were necessary to separately estimate the protein levels of the
      truncated (tr-NK-1R) and full-length (fl-NK-1R) receptors by
      immunohistochemistry. mRNA expression of tr-NK-1R increased 14-fold (P = 0.02)
      when comparing the HGD and CA groups. In contrast, the fl-NK-1R transcript showed
      no significant differences among groups. The protein levels of the total NK-1R
      increased by 40% (P = 0.02) in HGD and 80% (P = 0.0007) in CA compared with
      quiescent colitis. There were no significant changes in protein levels of the fl
      NK-1R. We conclude that the increase in total NK-1R protein in HGD and CA is
      attributable to an increase in tr-NK-1R, suggesting there may be a functional
      role for tr-NK-1R in malignant transformation in colitis-associated cancer. The
      tr-NK-1R could prove useful as a diagnostic marker to identify patients at risk
      for neoplasia and may serve as a useful therapeutic target in the treatment of
      colitis-associated cancer.

PMID- 21969572
TI  - Chris Raetz, scientist and enduring friend.

PMID- 21969573
TI  - Lipocalin-2 controls neuronal excitability and anxiety by regulating dendritic
      spine formation and maturation.
AB  - Psychological stress causes adaptive changes in the nervous system directed
      toward maintaining homoeostasis. These biochemical and structural mechanisms
      regulate animal behavior, and their malfunction may result in various forms of
      affective disorders. Here we found that the lipocalin-2 (Lcn2) gene, encoding a
      secreted protein of unknown neuronal function, was up-regulated in mouse
      hippocampus following psychological stress. Addition of lipocalin-2 to cultured
      hippocampal neurons reduced dendritic spine actin's mobility, caused retraction
      of mushroom spines, and inhibited spine maturation. These effects were further
      enhanced by inactivating iron-binding residues of Lcn-2, suggesting that they
      were facilitated by the iron-free form of Lcn-2. Concurrently, disruption of the
      Lcn2 gene in mice promoted stress-induced increase in spine density and caused an
      increase in the proportion of mushroom spines. The above changes correlated with
      higher excitability of CA1 principal neurons and with elevated stress-induced
      anxiety in Lcn-2(-/-) mice. Our study demonstrates that lipocalin-2 promotes
      stress-induced changes in spine morphology and function to regulate neuronal
      excitability and anxiety.

PMID- 21969574
TI  - Premotor synaptic plasticity limited to the critical period for song learning.
AB  - Synaptic plasticity has been hypothesized to underlie learning and memory.
      Understanding of how such plasticity might produce motor learning is limited, in
      part because of the paucity of model systems with a tractable learned behavior
      under control of a discrete neural circuit. Songbirds possess both of these
      traits, thereby providing an excellent model for studying vertebrate motor
      learning. We report unique evidence of long-term depression (LTD) in the juvenile
      songbird premotor robust nucleus of the arcopallium (RA). LTD induction at RA
      recurrent collateral synapses requires NMDA receptors, postsynaptic
      depolarization, and postsynaptic calcium, and can be reversed by high-frequency
      stimulation. In adult birds, which have exited the critical period for
      sensorimotor learning and cannot modify their song, we were no longer able to
      induce LTD at RA collateral synapses. Furthermore, testosterone-induced premature
      maturation of song in juveniles abolishes LTD. LTD in nucleus RA therefore makes
      an excellent candidate mechanism to mediate song learning during development and
      is well-suited to provide insight into other forms of vertebrate motor learning.

PMID- 21969575
TI  - Dosage-dependent phenotypes in models of 16p11.2 lesions found in autism.
AB  - Recurrent copy number variations (CNVs) of human 16p11.2 have been associated
      with a variety of developmental/neurocognitive syndromes. In particular, deletion
      of 16p11.2 is found in patients with autism, developmental delay, and obesity.
      Patients with deletions or duplications have a wide range of clinical features,
      and siblings carrying the same deletion often have diverse symptoms. To study the
      consequence of 16p11.2 CNVs in a systematic manner, we used chromosome
      engineering to generate mice harboring deletion of the chromosomal region
      corresponding to 16p11.2, as well as mice harboring the reciprocal duplication.
      These 16p11.2 CNV models have dosage-dependent changes in gene expression,
      viability, brain architecture, and behavior. For each phenotype, the consequence
      of the deletion is more severe than that of the duplication. Of particular note
      is that half of the 16p11.2 deletion mice die postnatally; those that survive to
      adulthood are healthy and fertile, but have alterations in the hypothalamus and
      exhibit a "behavior trap" phenotype-a specific behavior characteristic of rodents
      with lateral hypothalamic and nigrostriatal lesions. These findings indicate that
      16p11.2 CNVs cause brain and behavioral anomalies, providing insight into human
      neurodevelopmental disorders.

PMID- 21969576
TI  - The value of control and the influence of values.

PMID- 21969577
TI  - Transcriptional modulator H2A histone family, member Y (H2AFY) marks Huntington
      disease activity in man and mouse.
AB  - Huntington disease (HD) is a progressive neurodegenerative disease that affects
      30,000 individuals in North America. Treatments that slow its relentless course
      are not yet available, and biomarkers that can reliably measure disease activity
      and therapeutic response are urgently needed to facilitate their development.
      Here, we interrogated 119 human blood samples for transcripts associated with HD.
      We found that the dynamic regulator of chromatin plasticity H2A histone family,
      member Y (H2AFY) is specifically overexpressed in the blood and frontal cortex of
      patients with HD compared with controls. This association precedes the onset of
      clinical symptoms, was confirmed in two mouse models, and was independently
      replicated in cross-sectional and longitudinal clinical studies comprising 142
      participants. A histone deacetylase inhibitor that suppresses neurodegeneration
      in animal models reduces H2AFY levels in a randomized phase II clinical trial.
      This study identifies the chromatin regulator H2AFY as a potential biomarker
      associated with disease activity and pharmacodynamic response that may become
      useful for enabling disease-modifying therapeutics for HD.

PMID- 21969578
TI  - The causality analysis of climate change and large-scale human crisis.
AB  - Recent studies have shown strong temporal correlations between past climate
      changes and societal crises. However, the specific causal mechanisms underlying
      this relation have not been addressed. We explored quantitative responses of 14
      fine-grained agro-ecological, socioeconomic, and demographic variables to climate
      fluctuations from A.D. 1500-1800 in Europe. Results show that cooling from A.D.
      1560-1660 caused successive agro-ecological, socioeconomic, and demographic
      catastrophes, leading to the General Crisis of the Seventeenth Century. We
      identified a set of causal linkages between climate change and human crisis.
      Using temperature data and climate-driven economic variables, we simulated the
      alternation of defined "golden" and "dark" ages in Europe and the Northern
      Hemisphere during the past millennium. Our findings indicate that climate change
      was the ultimate cause, and climate-driven economic downturn was the direct
      cause, of large-scale human crises in preindustrial Europe and the Northern
      Hemisphere.

PMID- 21969580
TI  - Larval helpers and age polyethism in ambrosia beetles.
AB  - Division of labor among the workers of insect societies is a conspicuous feature
      of their biology. Social tasks are commonly shared among age groups but not
      between larvae and adults with completely different morphologies, as in bees,
      wasps, ants, and beetles (i.e., Holometabola). A unique yet hardly studied
      holometabolous group of insects is the ambrosia beetles. Along with one tribe of
      ants and one subfamily of termites, wood-dwelling ambrosia beetles are the only
      insect lineage culturing fungi, a trait predicted to favor cooperation and
      division of labor. Their sociality has not been fully demonstrated, because
      behavioral observations have been missing. Here we present behavioral data and
      experiments from within nests of an ambrosia beetle, Xyleborinus saxesenii.
      Larval and adult offspring of a single foundress cooperate in brood care, gallery
      maintenance, and fungus gardening, showing a clear division of labor between
      larval and adult colony members. Larvae enlarge the gallery and participate in
      brood care and gallery hygiene. The cooperative effort of adult females in the
      colony and the timing of their dispersal depend on the number of sibling
      recipients (larvae and pupae), on the presence of the mother, and on the number
      of adult workers. This suggests that altruistic help is triggered by demands of
      brood dependent on care. Thus, ambrosia beetles are not only highly social but
      also show a special form of division of labor that is unique among holometabolous
      insects.

PMID- 21969579
TI  - Microtubule-associated protein 1 light chain 3 alpha (LC3)-associated
      phagocytosis is required for the efficient clearance of dead cells.
AB  - The recognition and clearance of dead cells is a process that must occur
      efficiently to prevent an autoimmune or inflammatory response. Recently, a
      process was identified wherein the autophagy machinery is recruited to pathogen
      containing phagosomes, termed MAPLC3A (LC3)-associated phagocytosis (LAP), which
      results in optimal degradation of the phagocytosed cargo. Here, we describe the
      engagement of LAP upon uptake of apoptotic, necrotic, and RIPK3-dependent
      necrotic cells by macrophages. This process is dependent on some members of the
      classical autophagy pathway, including Beclin1, ATG5, and ATG7. In contrast,
      ULK1, despite being required for autophagy, is dispensable for LAP induced by
      uptake of microbes or dead cells. LAP is required for efficient degradation of
      the engulfed corpse, and in the absence of LAP, engulfment of dead cells results
      in increased production of proinflammatory cytokines and decreased production of
      anti-inflammatory cytokines. LAP is triggered by engagement of the TIM4 receptor
      by either phosphatidylserine (PtdSer)-displaying dead cells or PtdSer-containing
      liposomes. Therefore, the consequence of phagocytosis of dead cells is strongly
      affected by those components of the autophagy pathway involved in LAP.

PMID- 21969581
TI  - CCAAT/enhancer binding protein alpha (C/EBP(alpha))-induced transdifferentiation
      of pre-B cells into macrophages involves no overt retrodifferentiation.
AB  - Earlier work has shown that pre-B cells can be converted into macrophages by the
      transcription factor CCAAT/enhancer binding protein alpha at very high
      frequencies. Using this system, we performed a systematic analysis of whether
      during transdifferentiation the cells transiently reactivate progenitor
      restricted genes or even retrodifferentiate. A transcriptome analysis of
      transdifferentiating cells showed that most genes are up- or down-regulated
      continuously, acquiring a macrophage phenotype within 5 d. In addition, we
      observed the transient reactivation of a subset of immature myeloid markers, as
      well as low levels of the progenitor markers Kit and FMS-like tyrosine kinase 3
      and a few lineage-inappropriate genes. Importantly, however, we were unable to
      observe the reexpression of cell-surface marker combinations that characterize
      hematopoietic stem and progenitor cells, including c-Kit and FMS-like tyrosine
      kinase 3, even when CAAT/enhancer binding protein alpha was activated in pre-B
      cells under culture conditions that favor growth of hematopoietic stem and
      progenitor cells or when the transcription factor was activated in a time-limited
      fashion. Together, our findings are consistent with the notion that the
      conversion from pre-B cells to macrophages is mostly direct and does not involve
      overt retrodifferentiation.

PMID- 21969582
TI  - Antimicrobial resistance to ceftazidime involving loss of penicillin-binding
      protein 3 in Burkholderia pseudomallei.
AB  - Known mechanisms of resistance to beta-lactam antibiotics include beta-lactamase
      expression, altered drug target, decreased bacterial permeability, and increased
      drug efflux. Here, we describe a unique mechanism of beta-lactam resistance in
      the biothreat organism Burkholderia pseudomallei (the cause of melioidosis),
      associated with treatment failure during prolonged ceftazidime therapy of natural
      infection. Detailed comparisons of the initial ceftazidime-susceptible infecting
      isolate and subsequent ceftazidime-resistant variants from six patients led us to
      identify a common, large-scale genomic loss involving a minimum of 49 genes in
      all six resistant strains. Mutational analysis of wild-type B. pseudomallei
      demonstrated that ceftazidime resistance was due to deletion of a gene encoding a
      penicillin-binding protein 3 (BPSS1219) present within the region of genomic
      loss. The clinical ceftazidime-resistant variants failed to grow using commonly
      used laboratory culture media, including commercial blood cultures, rendering the
      variants almost undetectable in the diagnostic laboratory. Melioidosis is
      notoriously difficult to cure and clinical treatment failure is common in
      patients treated with ceftazidime, the drug of first choice across most of
      Southeast Asia where the majority of cases are reported. The mechanism described
      here represents an explanation for ceftazidime treatment failure, and may be a
      frequent but undetected resistance event.

PMID- 21969583
TI  - Tissue-intrinsic dysfunction of circadian clock confers transplant
      arteriosclerosis.
AB  - The suprachiasmatic nucleus of the brain is the circadian center, relaying
      rhythmic environmental and behavioral information to peripheral tissues to
      control circadian physiology. As such, central clock dysfunction can alter
      systemic homeostasis to consequently impair peripheral physiology in a manner
      that is secondary to circadian malfunction. To determine the impact of circadian
      clock function in organ transplantation and dissect the influence of intrinsic
      tissue clocks versus extrinsic clocks, we implemented a blood vessel grafting
      approach to surgically assemble a chimeric mouse that was part wild-type (WT) and
      part circadian clock mutant. Arterial isografts from donor WT mice that had been
      anastamosed to common carotid arteries of recipient WT mice (WT:WT) exhibited no
      pathology in this syngeneic transplant strategy. Similarly, when WT grafts were
      anastamosed to mice with disrupted circadian clocks, the structural features of
      the WT grafts immersed in the milieu of circadian malfunction were normal and
      absent of lesions, comparable to WT:WT grafts. In contrast, aortic grafts from
      Bmal1 knockout (KO) or Period-2,3 double-KO mice transplanted into littermate
      control WT mice developed robust arteriosclerotic disease. These lesions observed
      in donor grafts of Bmal1-KO were associated with up-regulation in T-cell
      receptors, macrophages, and infiltrating cells in the vascular grafts, but were
      independent of hemodynamics and B and T cell-mediated immunity. These data
      demonstrate the significance of intrinsic tissue clocks as an autonomous
      influence in experimental models of arteriosclerotic disease, which may have
      implications with regard to the influence of circadian clock function in organ
      transplantation.

PMID- 21969584
TI  - Caenorhabditis elegans selects distinct crawling and swimming gaits via dopamine
      and serotonin.
AB  - Many animals, including humans, select alternate forms of motion (gaits) to move
      efficiently in different environments. However, it is unclear whether primitive
      animals, such as nematodes, also use this strategy. We used a multifaceted
      approach to study how the nematode Caenorhabditis elegans freely moves into and
      out of water. We demonstrate that C. elegans uses biogenic amines to switch
      between distinct crawling and swimming gaits. Dopamine is necessary and
      sufficient to initiate and maintain crawling after swimming. Serotonin is
      necessary and sufficient to transition from crawling to swimming and to inhibit a
      set of crawl-specific behaviors. Further study of locomotory switching in C.
      elegans and its dependence on biogenic amines may provide insight into how gait
      transitions are performed in other animals.

PMID- 21969585
TI  - QnAs with Cynthia Kenyon.

PMID- 21969586
TI  - Astrocytes carrying the superoxide dismutase 1 (SOD1G93A) mutation induce wild
      type motor neuron degeneration in vivo.
AB  - Recent studies highlight astrocytes as key drivers of motor neuron (MN)
      degeneration and disease propagation in mutant human superoxide dismutase 1
      (mSOD1)-mediated amyotrophic lateral sclerosis. However, in vivo analysis of
      specific astrocytic influence in amyotrophic lateral sclerosis has proven
      difficult because mSOD1 is ubiquitously expressed throughout the CNS of rodent
      models studied. Here, we transplanted SOD1(G93A) glial-restricted precursor cells
      -glial progenitors capable of differentiating into astrocytes--into the cervical
      spinal cord of WT rats to reveal how mutant astrocytes influence WT MNs and other
      cells types (microglia and astrocytes) in an in vivo setting. Transplanted
      SOD1(G93A) glial-restricted precursor cells survived and differentiated
      efficiently into astrocytes. Graft-derived SOD1(G93A) astrocytes induced host MN
      ubiquitination and death, forelimb motor and respiratory dysfunction, reactive
      astrocytosis, and reduced GLT-1 transporter expression in WT animals. The
      SOD1(G93A) astrocyte-induced MN death seemed in part mediated by host microglial
      activation. These findings show that mSOD1 astrocytes alone can induce WT MN
      death and associated pathological changes in vivo.

PMID- 21969587
TI  - Full activity of the deleted in liver cancer 1 (DLC1) tumor suppressor depends on
      an LD-like motif that binds talin and focal adhesion kinase (FAK).
AB  - The deleted in liver cancer 1 (DLC1) tumor suppressor gene, which is frequently
      inactivated in cancer, encodes a Rho-GAP (GTPase activating protein) focal
      adhesion protein whose negative regulation of Rho-GTPases is necessary but not
      sufficient for its full tumor suppressor activity. Here, we report that DLC1
      forms a complex with two prooncogenic focal adhesion proteins, talin and the
      focal adhesion kinase (FAK). We identified an 8-aa sequence (residues
      469LDDILYHV476) in DLC1 and designated it an LD-like motif, because it shares
      homology with the LD motifs of paxillin. This motif was necessary for DLC1
      binding to talin and FAK, because a DLC1 mutant, from which six of the residues
      have been deleted, and another mutant carrying amino acid substitutions in three
      of the residues are deficient for binding both proteins and localization of DLC1
      to focal adhesions. FAK binding was independent of talin and vice versa. In
      bioassays, both DLC1 mutants were less active than wild-type (WT) DLC1, although
      the ability of the mutants to negatively regulate overall Rho-GTP was not
      impaired. We conclude that the LD-like motif, which binds talin and FAK, is
      required for the full tumor suppressor activity of DLC1 and contributes to the
      association of DLC1 with focal adhesions.

PMID- 21969588
TI  - Interspecific Y chromosome introgressions disrupt testis-specific gene expression
      and male reproductive phenotypes in Drosophila.
AB  - The Drosophila Y chromosome is a degenerated, heterochromatic chromosome with few
      functional genes. Nonetheless, natural variation on the Y chromosome in
      Drosophila melanogaster has substantial trans-acting effects on the regulation of
      X-linked and autosomal genes. However, the contribution of Y chromosome
      divergence to gene expression divergence between species is unknown. In this
      study, we constructed a series of Y chromosome introgression lines, in which Y
      chromosomes from either Drosophila sechellia or Drosophila simulans are
      introgressed into a common D. simulans genetic background. Using these lines, we
      compared genome-wide gene expression and male reproductive phenotypes between
      heterospecific and conspecific Y chromosomes. We find significant differences in
      expression for 122 genes, or 2.84% of all genes analyzed. Genes down-regulated in
      males with heterospecific Y chromosomes are significantly biased toward testis
      specific expression patterns. These same lines show reduced fecundity and sperm
      competitive ability. Taken together, these results imply a significant role for
      Y/X and Y/autosome interactions in maintaining proper expression of male-specific
      genes, either directly or via indirect effects on male reproductive tissue
      development or function.

PMID- 21969589
TI  - Cell culture model that mimics drusen formation and triggers complement
      activation associated with age-related macular degeneration.
AB  - We introduce a human retinal pigmented epithelial (RPE) cell-culture model that
      mimics several key aspects of early stage age-related macular degeneration (AMD).
      These include accumulation of sub-RPE deposits that contain molecular
      constituents of human drusen, and activation of complement leading to formation
      of deposit-associated terminal complement complexes. Abundant sub-RPE deposits
      that are rich in apolipoprotein E (APOE), a prominent drusen constituent, are
      formed by RPE cells grown on porous supports. Exposure to human serum results in
      selective, deposit-associated accumulation of additional known drusen components,
      including vitronectin, clusterin, and serum amyloid P, thus suggesting that
      specific protein-protein interactions contribute to the accretion of plasma
      proteins during drusen formation. Serum exposure also leads to complement
      activation, as evidenced by the generation of C5b-9 immunoreactive terminal
      complement complexes in association with APOE-containing deposits.
      Ultrastructural analyses reveal two morphologically distinct forms of deposits:
      One consisting of membrane-bounded multivesicular material, and the other of
      nonmembrane-bounded particle conglomerates. Collectively, these results suggest
      that drusen formation involves the accumulation of sub-RPE material rich in APOE,
      a prominent biosynthetic product of the RPE, which interacts with a select group
      of drusen-associated plasma proteins. Activation of the complement cascade
      appears to be mediated via the classical pathway by the binding of C1q to ligands
      in APOE-rich deposits, triggering direct activation of complement by C1q,
      deposition of terminal complement complexes and inflammatory sequelae. This model
      system will facilitate the analysis of molecular and cellular aspects of AMD
      pathogenesis, and the testing of new therapeutic agents for its treatment.

PMID- 21969590
TI  - Macrophage migration inhibitory factor (MIF) exerts antifibrotic effects in
      experimental liver fibrosis via CD74.
AB  - Macrophage migration inhibitory factor (MIF) is a pleiotropic inflammatory
      cytokine that has been implicated in various inflammatory diseases. Chronic
      inflammation is a mainstay of liver fibrosis, a leading cause of morbidity
      worldwide, but the role of MIF in liver scarring has not yet been elucidated.
      Here we have uncovered an unexpected antifibrotic role for MIF. Mice genetically
      deleted in Mif (Mif(-/-)) showed strongly increased fibrosis in two models of
      chronic liver injury. Pronounced liver fibrosis in Mif(-/-) mice was associated
      with alterations in fibrosis-relevant genes, but not by a changed intrahepatic
      immune cell infiltration. Next, a direct impact of MIF on hepatic stellate cells
      (HSC) was assessed in vitro. Although MIF alone had only marginal effects on
      HSCs, it markedly inhibited PDGF-induced migration and proliferation of these
      cells. The inhibitory effects of MIF were mediated by CD74, which we detected as
      the most abundant known MIF receptor on HSCs. MIF promoted the phosphorylation of
      AMP-activated protein kinase (AMPK) in a CD74-dependent manner and, in turn,
      inhibition of AMPK reversed the inhibition of PDGF-induced HSC activation by MIF.
      The pivotal role of CD74 in MIF-mediated antifibrotic properties was further
      supported by augmented liver scarring of Cd74(-/-) mice. Moreover, mice treated
      with recombinant MIF displayed a reduced fibrogenic response in vivo. In
      conclusion, we describe a previously unexplored antifibrotic function of MIF that
      is mediated by the CD74/AMPK signaling pathway in HSCs. The results imply MIF and
      CD74 as targets for treatment of liver diseases.

PMID- 21969591
TI  - Maintenance of hormone responsiveness in luminal breast cancers by suppression of
      Notch.
AB  - Luminal breast cancers express estrogen (ER) and/or progesterone (PR) receptors
      and respond to hormone therapies. Basal-like "triple negative" cancers lack
      steroid receptors but are cytokeratin (CK) 5-positive and require chemotherapy.
      Here we show that more than half of primary ER(+)PR(+) breast cancers contain an
      ER(-)PR(-)CK5(+) "luminobasal" subpopulation exceeding 1% of cells. Starting from
      ER(+)PR(+) luminal cell lines, we generated lines with varying luminal to
      luminobasal cell ratios and studied their molecular and biological properties. In
      luminal disease, luminobasal cells expand in response to antiestrogen or estrogen
      withdrawal therapies. The phenotype and gene signature of the hormone-resistant
      cells matches that of clinical triple negative basal-like and claudin-low
      disease. Luminobasal cell expansion in response to hormone therapies is regulated
      by Notch1 signaling and can be blocked by gamma-secretase inhibitors. Our data
      establish a previously unrecognized plasticity of ER(+)PR(+) luminal breast
      cancers that, without genetic manipulation, mobilizes outgrowth of hormone
      resistant basal-like disease in response to treatment. This undesirable outcome
      can be prevented by combining endocrine therapies with Notch inhibition.

PMID- 21969592
TI  - Tumor suppressor down-regulated in renal cell carcinoma 1 (DRR1) is a stress
      induced actin bundling factor that modulates synaptic efficacy and cognition.
AB  - Stress has been identified as a major causal factor for many mental disorders.
      However, our knowledge about the chain of molecular and cellular events
      translating stress experience into altered behavior is still rather scant. Here,
      we have characterized a murine ortholog of the putative tumor suppressor gene
      DRR1 as a unique stress-induced protein in brain. It binds to actin, promotes
      bundling and stabilization of actin filaments, and impacts on actin-dependent
      neurite outgrowth. Endogenous DRR1 localizes to some, but not all, synapses, with
      preference for the presynaptic region. Hippocampal virus-mediated enhancement of
      DRR1 expression reduced spine density, diminished the probability of synaptic
      glutamate release, and altered cognitive performance. DRR1 emerges as a protein
      to link stress with actin dynamics, which in addition is able to act on synaptic
      function and cognition.

PMID- 21969594
TI  - Antibiotic acyldepsipeptides activate ClpP peptidase to degrade the cell division
      protein FtsZ.
AB  - The worldwide spread of antibiotic-resistant bacteria has lent urgency to the
      search for antibiotics with new modes of action that are devoid of preexisting
      cross-resistances. We previously described a unique class of acyldepsipeptides
      (ADEPs) that exerts prominent antibacterial activity against Gram-positive
      pathogens including streptococci, enterococci, as well as multidrug-resistant
      Staphylococcus aureus. Here, we report that ADEP prevents cell division in Gram
      positive bacteria and induces strong filamentation of rod-shaped Bacillus
      subtilis and swelling of coccoid S. aureus and Streptococcus pneumoniae. It
      emerged that ADEP treatment inhibits septum formation at the stage of Z-ring
      assembly, and that central cell division proteins delocalize from midcell
      positions. Using in vivo and in vitro studies, we show that the inhibition of Z
      ring formation is a consequence of the proteolytic degradation of the essential
      cell division protein FtsZ. ADEP switches the bacterial ClpP peptidase from a
      regulated to an uncontrolled protease, and it turned out that FtsZ is
      particularly prone to degradation by the ADEP-ClpP complex. By preventing cell
      division, ADEP inhibits a vital cellular process of bacteria that is not targeted
      by any therapeutically applied antibiotic so far. Their unique multifaceted
      mechanism of action and antibacterial potency makes them promising lead
      structures for future antibiotic development.

PMID- 21969595
TI  - Lymphomas that recur after MYC suppression continue to exhibit oncogene
      addiction.
AB  - The suppression of oncogenic levels of MYC is sufficient to induce sustained
      tumor regression associated with proliferative arrest, differentiation, cellular
      senescence, and/or apoptosis, a phenomenon known as oncogene addiction. However,
      after prolonged inactivation of MYC in a conditional transgenic mouse model of
      EMU-tTA/tetO-MYC T-cell acute lymphoblastic leukemia, some of the tumors recur,
      recapitulating what is frequently observed in human tumors in response to
      targeted therapies. Here we report that these recurring lymphomas express either
      transgenic or endogenous Myc, albeit in many cases at levels below those in the
      original tumor, suggesting that tumors continue to be addicted to MYC. Many of
      the recurring lymphomas (76%) harbored mutations in the tetracycline
      transactivator, resulting in expression of the MYC transgene even in the presence
      of doxycycline. Some of the remaining recurring tumors expressed high levels of
      endogenous Myc, which was associated with a genomic rearrangement of the
      endogenous Myc locus or activation of Notch1. By gene expression profiling, we
      confirmed that the primary and recurring tumors have highly similar
      transcriptomes. Importantly, shRNA-mediated suppression of the high levels of MYC
      in recurring tumors elicited both suppression of proliferation and increased
      apoptosis, confirming that these tumors remain oncogene addicted. These results
      suggest that tumors induced by MYC remain addicted to overexpression of this
      oncogene.

PMID- 21969596
TI  - Ablation of a galectin preferentially expressed in adipocytes increases
      lipolysis, reduces adiposity, and improves insulin sensitivity in mice.
AB  - The breakdown of triglycerides, or lipolysis, is a tightly controlled process
      that regulates fat mobilization in accord with an animal's energy needs. It is
      well established that lipolysis is stimulated by hormones that signal energy
      demand and is suppressed by the antilipolytic hormone insulin. However, much
      still remains to be learned about regulation of lipolysis by intracellular
      signaling pathways in adipocytes. Here we show that galectin-12, a member of a
      beta-galactoside-binding lectin family preferentially expressed by adipocytes,
      functions as an intrinsic negative regulator of lipolysis. Galectin-12 is
      primarily localized on lipid droplets and regulates lipolytic protein kinase A
      signaling by acting upstream of phosphodiesterase activity to control cAMP
      levels. Ablation of galectin-12 in mice results in increased adipocyte
      mitochondrial respiration, reduced adiposity, and ameliorated insulin
      resistance/glucose intolerance. This study identifies unique properties of this
      intracellular galectin that is localized to an organelle and performs a critical
      function in lipid metabolism. These findings add to the significant functions
      exhibited by intracellular galectins, and have important therapeutic implications
      for human metabolic disorders.

PMID- 21969597
TI  - Nanoparticle conjugation of antigen enhances cytotoxic T-cell responses in
      pulmonary vaccination.
AB  - The ability of vaccines to induce memory cytotoxic T-cell responses in the lung
      is crucial in stemming and treating pulmonary diseases caused by viruses and
      bacteria. However, most approaches to subunit vaccines produce primarily humoral
      and only to a lesser extent cellular immune responses. We developed a
      nanoparticle (NP)-based carrier that, upon delivery to the lung, specifically
      targets pulmonary dendritic cells, thus enhancing antigen uptake and transport to
      the draining lymph node; antigen coupling via a disulfide link promotes highly
      efficient cross-presentation after uptake, inducing potent protective mucosal and
      systemic CD8(+) T-cell immunity. Pulmonary immunization with NP-conjugated
      ovalbumin (NP-ova) with CpG induced a threefold enhancement of splenic antigen
      specific CD8(+) T cells displaying increased CD107a expression and IFN-gamma
      production compared with immunization with soluble (i.e., unconjugated) ova with
      CpG. This enhanced response was accompanied by a potent Th17 cytokine profile in
      CD4(+) T cells. After 50 d, NP-ova and CpG also led to substantial enhancements
      in memory CD8(+) T-cell effector functions. Importantly, pulmonary vaccination
      with NP-ova and CpG induced as much as 10-fold increased frequencies of antigen
      specific effector CD8(+) T cells to the lung and completely protected mice from
      morbidity following influenza-ova infection. Here, we highlight recruitment to
      the lung of a long-lasting pool of protective effector memory cytotoxic T-cells
      by our disulfide-linked antigen-conjugated NP formulation. These results suggest
      the reduction-reversible NP system is a highly promising platform for vaccines
      specifically targeting intracellular pathogens infecting the lung.

PMID- 21969598
TI  - Animal-specific C-terminal domain links myeloblastosis oncoprotein (Myb) to an
      ancient repressor complex.
AB  - Members of the Myb oncoprotein and E2F-Rb tumor suppressor protein families are
      present within the same highly conserved multiprotein transcriptional repressor
      complex, named either as Myb and synthetic multivuval class B (Myb-MuvB) or as
      Drosophila Rb E2F and Myb-interacting proteins (dREAM). We now report that the
      animal-specific C terminus of Drosophila Myb but not the more highly conserved N
      terminal DNA-binding domain is necessary and sufficient for (i) adult viability,
      (ii) proper localization to chromosomes in vivo, (iii) regulation of gene
      expression in vivo, and (iv) interaction with the highly conserved core of the
      MuvB/dREAM transcriptional repressor complex. In addition, we have identified a
      conserved peptide motif that is required for this interaction. Our results imply
      that an ancient function of Myb in regulating G2/M genes in both plants and
      animals appears to have been transferred from the DNA-binding domain to the
      animal-specific C-terminal domain. Increased expression of B-MYB/MYBL2, the human
      ortholog of Drosophila Myb, correlates with poor prognosis in human patients with
      breast cancer. Therefore, our results imply that the specific interaction of the
      C terminus of Myb with the MuvB/dREAM core complex may provide an attractive
      target for the development of cancer therapeutics.

PMID- 21969599
TI  - Targeted nanoparticle enhanced proapoptotic peptide as potential therapy for
      glioblastoma.
AB  - Antiangiogenic therapy can produce transient tumor regression in glioblastoma
      (GBM), but no prolongation in patient survival has been achieved. We have
      constructed a nanosystem targeted to tumor vasculature that incorporates three
      elements: (i) a tumor-homing peptide that specifically delivers its payload to
      the mitochondria of tumor endothelial cells and tumor cells, (ii) conjugation of
      this homing peptide with a proapoptotic peptide that acts on mitochondria, and
      (iii) multivalent presentation on iron oxide nanoparticles, which enhances the
      proapoptotic activity. The iron oxide component of the nanoparticles enabled
      imaging of GBM tumors in mice. Systemic treatment of GBM-bearing mice with the
      nanoparticles eradicated most tumors in one GBM mouse model and significantly
      delayed tumor development in another. Coinjecting the nanoparticles with a tumor
      penetrating peptide further enhanced the therapeutic effect. Both models used
      have proven completely resistant to other therapies, suggesting clinical
      potential of our nanosystem.

PMID- 21969600
TI  - Retraction for Garman et al: A genomic approach to colon cancer risk
      stratification yields biologic insights into therapeutic opportunities.

PMID- 21969601
TI  - Hypoxia potentiates microRNA-mediated gene silencing through posttranslational
      modification of Argonaute2.
AB  - Hypoxia contributes to the pathogenesis of various human diseases, including
      pulmonary artery hypertension (PAH), stroke, myocardial or cerebral infarction,
      and cancer. For example, acute hypoxia causes selective pulmonary artery (PA)
      constriction and elevation of pulmonary artery pressure. Chronic hypoxia induces
      structural and functional changes to the pulmonary vasculature, which resembles
      the phenotype of human PAH and is commonly used as an animal model of this
      disease. The mechanisms that lead to hypoxia-induced phenotypic changes have not
      been fully elucidated. Here, we show that hypoxia increases type I collagen
      prolyl-4-hydroxylase [C-P4H(I)], which leads to prolyl-hydroxylation and
      accumulation of Argonaute2 (Ago2), a critical component of the RNA-induced
      silencing complex (RISC). Hydroxylation of Ago2 is required for the association
      of Ago2 with heat shock protein 90 (Hsp90), which is necessary for the loading of
      microRNAs (miRNAs) into the RISC, and translocation to stress granules (SGs). We
      demonstrate that hydroxylation of Ago2 increases the level of miRNAs and
      increases the endonuclease activity of Ago2. In summary, this study identifies
      hypoxia as a mediator of the miRNA-dependent gene silencing pathway through
      posttranslational modification of Ago2, which might be responsible for cell
      survival or pathological responses under low oxygen stress.

PMID- 21969602
TI  - The NF90/NF45 complex participates in DNA break repair via nonhomologous end
      joining.
AB  - Nuclear factor 90 (NF90), an RNA-binding protein implicated in the regulation of
      gene expression, exists as a heterodimeric complex with NF45. We previously
      reported that depletion of the NF90/NF45 complex results in a multinucleated
      phenotype. Time-lapse microscopy revealed that binucleated cells arise by
      incomplete abscission of progeny cells followed by fusion. Multinucleate cells
      arose through aberrant division of binucleated cells and displayed abnormal
      metaphase plates and anaphase chromatin bridges suggestive of DNA repair defects.
      NF90 and NF45 are known to interact with the DNA-dependent protein kinase (DNA
      PK), which is involved in telomere maintenance and DNA repair by nonhomologous
      end joining (NHEJ). We hypothesized that NF90 modulates the activity of DNA-PK.
      In an in vitro NHEJ assay system, DNA end joining was reduced by NF90/NF45
      immunodepletion or by RNA digestion to an extent similar to that for catalytic
      subunit DNA-PKcs immunodepletion. In vivo, NF90/NF45-depleted cells displayed
      increased gamma-histone 2A.X foci, indicative of an accumulation of double-strand
      DNA breaks (DSBs), and increased sensitivity to ionizing radiation consistent
      with decreased DSB repair. Further, NF90/NF45 knockdown reduced end-joining
      activity in vivo. These results identify the NF90/NF45 complex as a regulator of
      DNA damage repair mediated by DNA-PK and suggest that structured RNA may modulate
      this process.

PMID- 21969603
TI  - Dynamic nucleosome-depleted regions at androgen receptor enhancers in the absence
      of ligand in prostate cancer cells.
AB  - Nucleosome positioning at transcription start sites is known to regulate gene
      expression by altering DNA accessibility to transcription factors; however, its
      role at enhancers is poorly understood. We investigated nucleosome positioning at
      the androgen receptor (AR) enhancers of TMPRSS2, KLK2, and KLK3/PSA in prostate
      cancer cells. Surprisingly, a population of enhancer modules in androgen-deprived
      cultures showed nucleosome-depleted regions (NDRs) in all three loci. Under
      androgen-deprived conditions, NDRs at the TMPRSS2 enhancer were maintained by the
      pioneer AR transcriptional collaborator GATA-2. Androgen treatment resulted in AR
      occupancy, an increased number of enhancer modules with NDRs without changes in
      footprint width, increased levels of histone H3 acetylation (AcH3), and
      dimethylation (H3K4me2) at nucleosomes flanking the NDRs. Our data suggest that,
      in the absence of ligand, AR enhancers exist in an equilibrium in which a
      percentage of modules are occupied by nucleosomes while others display NDRs. We
      propose that androgen treatment leads to the disruption of the equilibrium toward
      a nucleosome-depleted state, rather than to enhancer de novo "remodeling." This
      allows the recruitment of histone modifiers, chromatin remodelers, and ultimately
      gene activation. The "receptive" state described here could help explain AR
      signaling activation under very low ligand concentrations.

PMID- 21969604
TI  - Identification of RhoGAP22 as an Akt-dependent regulator of cell motility in
      response to insulin.
AB  - Insulin exerts many of its metabolic actions via the canonical
      phosphatidylinositide 3 kinase (PI3K)/Akt pathway, leading to phosphorylation and
      14-3-3 binding of key metabolic targets. We previously identified a GTPase
      activating protein (GAP) for Rac1 called RhoGAP22 as an insulin-responsive 14-3-3
      binding protein. Insulin increased 14-3-3 binding to RhoGAP22 fourfold, and this
      effect was PI3K dependent. We identified two insulin-responsive 14-3-3 binding
      sites (pSer(16) and pSer(395)) within RhoGAP22, and mutagenesis studies revealed
      a complex interplay between the phosphorylation at these two sites. Mutating
      Ser(16) to alanine blocked 14-3-3 binding to RhoGAP22 in vivo, and
      phosphorylation at Ser(16) was mediated by the kinase Akt. Overexpression of a
      mutant RhoGAP22 that was unable to bind 14-3-3 reduced cell motility in NIH-3T3
      fibroblasts, and this effect was dependent on a functional GAP domain. Mutation
      of the catalytic arginine of the GAP domain of RhoGAP22 potentiated growth factor
      stimulated Rac1 GTP loading. We propose that insulin and possibly growth factors
      such as platelet-derived growth factor may play a novel role in regulating cell
      migration and motility via the Akt-dependent phosphorylation of RhoGAP22, leading
      to modulation of Rac1 activity.

PMID- 21969605
TI  - Extranucleosomal DNA binding directs nucleosome sliding by Chd1.
AB  - Chd1- and ISWI-type chromatin remodelers can sense extranucleosomal DNA and
      preferentially shift nucleosomes toward longer stretches of available DNA. The
      DNA-binding domains of these chromatin remodelers are believed to be responsible
      for sensing extranucleosomal DNA and are needed for robust sliding, but it is
      unclear how these domains contribute to directional movement of nucleosomes.
      Here, we show that the DNA-binding domain of Chd1 is not essential for nucleosome
      sliding but is critical for centering mononucleosomes on short DNA fragments.
      Remarkably, nucleosome centering was achieved by replacing the native DNA-binding
      domain of Chd1 with foreign DNA-binding domains of Escherichia coli AraC or
      Drosophila melanogaster engrailed. Introducing target DNA sequences recognized by
      the foreign domains enabled the remodelers to rapidly shift nucleosomes toward
      these binding sites, demonstrating that these foreign DNA-binding domains
      dictated the direction of sliding. Sequence-directed sliding occluded the target
      DNA sequences on the nucleosome enough to promote release of the remodeler.
      Target DNA sequences were highly stimulatory at multiple positions flanking the
      nucleosome and had the strongest influence when separated from the nucleosome by
      23 or fewer base pairs. These results suggest that the DNA-binding domain's
      affinity for extranucleosomal DNA is the key determinant for the direction that
      Chd1 shifts the nucleosome.

PMID- 21969606
TI  - Chlamydia trachomatis inclusions induce asymmetric cleavage furrow formation and
      ingression failure in host cells.
AB  - Chlamydia trachomatis infection has been suggested to induce host genome
      duplication and is linked to increased risks of cervical cancer. We describe here
      the mechanism by which Chlamydia causes a cleavage furrow defect that
      consistently results in the formation of multinucleated host cells, a phenomenon
      linked to tumorigenesis. Host signaling proteins essential for cleavage furrow
      initiation, ingression, and stabilization are displaced from one of the
      prospective furrowing cortices after Chlamydia infection. This protein
      displacement leads to the formation of a unique asymmetrical, unilateral cleavage
      furrow in infected human cells. The asymmetrical distribution of signaling
      proteins is caused by the physical presence of the Chlamydia inclusion at the
      cell equator. By using ingested latex beads, we demonstrate that the presence of
      a large vacuole at the cell equator is sufficient to cause furrow ingression
      failure and can lead to multinucleation. Interestingly, internalized latex beads
      of similar size do not localize to the cell equator as efficiently as Chlamydia
      inclusions; moreover, inhibition of bacterial protein synthesis with antibiotic
      reduces the frequency at which Chlamydia localizes to the cell equator. Together,
      these results suggest that Chlamydia effectors are involved in strategic
      positioning of the inclusion during cell division.

PMID- 21969607
TI  - Tyrosine phosphorylation of lactate dehydrogenase A is important for NADH/NAD(+)
      redox homeostasis in cancer cells.
AB  - The Warburg effect describes an increase in aerobic glycolysis and enhanced
      lactate production in cancer cells. Lactate dehydrogenase A (LDH-A) regulates the
      last step of glycolysis that generates lactate and permits the regeneration of
      NAD(+). LDH-A gene expression is believed to be upregulated by both HIF and Myc
      in cancer cells to achieve increased lactate production. However, how oncogenic
      signals activate LDH-A to regulate cancer cell metabolism remains unclear. We
      found that the oncogenic receptor tyrosine kinase FGFR1 directly phosphorylates
      LDH-A. Phosphorylation at Y10 and Y83 enhances LDH-A activity by enhancing the
      formation of active, tetrameric LDH-A and the binding of LDH-A substrate NADH,
      respectively. Moreover, Y10 phosphorylation of LDH-A is common in diverse human
      cancer cells, which correlates with activation of multiple oncogenic tyrosine
      kinases. Interestingly, cancer cells with stable knockdown of endogenous LDH-A
      and rescue expression of a catalytic hypomorph LDH-A mutant, Y10F, demonstrate
      increased respiration through mitochondrial complex I to sustain glycolysis by
      providing NAD(+). However, such a compensatory increase in mitochondrial
      respiration in Y10F cells is insufficient to fully sustain glycolysis. Y10 rescue
      cells show decreased cell proliferation and ATP levels under hypoxia and reduced
      tumor growth in xenograft nude mice. Our findings suggest that tyrosine
      phosphorylation enhances LDH-A enzyme activity to promote the Warburg effect and
      tumor growth by regulating the NADH/NAD(+) redox homeostasis, representing an
      acute molecular mechanism underlying the enhanced lactate production in cancer
      cells.

PMID- 21969608
TI  - The origin of proteasome-inhibitor resistant HLA class I peptidomes: a study with
      HLA-A*68:01.
AB  - Some HLA class I molecules bind a significant fraction of their constitutive
      peptidomes in the presence of proteasome inhibitors. In this study, A*68:01-bound
      peptides, and their parental proteins, were characterized through massive mass
      spectrometry sequencing to refine its binding motif, including the nearly
      exclusive preference for C-terminal basic residues. Stable isotope tagging was
      used to distinguish proteasome-inhibitor sensitive and resistant ligands. The
      latter accounted for less than 20% of the peptidome and, like in HLA-B27, arose
      predominantly from small and basic proteins. Under the conditions used for
      proteasome inhibition in vivo, epoxomicin and MG-132 incompletely inhibited the
      hydrolysis of fluorogenic substrates specific for the tryptic or for both the
      tryptic and chymotryptic subspecificities, respectively. This incomplete
      inhibition was also reflected in the cleavage of synthetic peptide precursors of
      A*68:01 ligands. For these substrates, the inhibition of the proteasome resulted
      in altered cleavage patterns. However these alterations did not upset the balance
      between cleavage at peptide bonds resulting in epitope destruction and those
      leading to their generation. The results indicate that inhibitor-resistant HLA
      class I ligands are not necessarily produced by non-proteasomal pathways.
      However, their generation is not simply explained by decreased epitope
      destruction upon incomplete proteasomal inhibition and may require additional
      proteolytic steps acting on incompletely processed proteasomal products.

PMID- 21969611
TI  - Editorial: from data to results.

PMID- 21969609
TI  - Proteogenomic analysis of Mycobacterium tuberculosis by high resolution mass
      spectrometry.
AB  - The genome sequencing of H37Rv strain of Mycobacterium tuberculosis was completed
      in 1998 followed by the whole genome sequencing of a clinical isolate, CDC1551 in
      2002. Since then, the genomic sequences of a number of other strains have become
      available making it one of the better studied pathogenic bacterial species at the
      genomic level. However, annotation of its genome remains challenging because of
      high GC content and dissimilarity to other model prokaryotes. To this end, we
      carried out an in-depth proteogenomic analysis of the M. tuberculosis H37Rv
      strain using Fourier transform mass spectrometry with high resolution at both MS
      and tandem MS levels. In all, we identified 3176 proteins from Mycobacterium
      tuberculosis representing ~80% of its total predicted gene count. In addition to
      protein database search, we carried out a genome database search, which led to
      identification of ~250 novel peptides. Based on these novel genome search
      specific peptides, we discovered 41 novel protein coding genes in the H37Rv
      genome. Using peptide evidence and alternative gene prediction tools, we also
      corrected 79 gene models. Finally, mass spectrometric data from N terminus
      derived peptides confirmed 727 existing annotations for translational start sites
      while correcting those for 33 proteins. We report creation of a high confidence
      set of protein coding regions in Mycobacterium tuberculosis genome obtained by
      high resolution tandem mass-spectrometry at both precursor and fragment detection
      steps for the first time. This proteogenomic approach should be generally
      applicable to other organisms whose genomes have already been sequenced for
      obtaining a more accurate catalogue of protein-coding genes.

PMID- 21969613
TI  - The war against bacteria: how were sulphonamide drugs used by Britain during
      World War II?
AB  - Penicillin is often considered one of the greatest discoveries of 20th century
      medicine. However, the revolution in therapeutics brought about by sulphonamides
      also had a profound effect on British medicine, particularly during World War II
      (WWII). Sulphonamides were used to successfully treat many infections which later
      yielded to penicillin and so their role deserves wider acknowledgement. The
      sulphonamides, a pre-war German discovery, were widely used clinically. However,
      the revolution brought about by the drugs has been either neglected or obscured
      by penicillin, resulting in less research on their use in Britain during WWII. By
      examining Medical Research Council records, particularly war memorandums, as well
      as medical journals, archives and newspaper reports, this paper hopes to
      highlight the importance of the sulphonamides and demonstrate their critical role
      in the medical war effort and their importance in both the public and more
      particularly, the medical, sectors. It will present evidence to show that
      sulphonamides gained importance due to the increased prevalence of infection
      which compromised the health of servicemen during WWII. The frequency of these
      infections led to an increase in demand and production. However, the
      sulphonamides were soon surpassed by penicillin, which had fewer side-effects and
      could treat syphilis and sulphonamide-resistant infections. Nevertheless, despite
      these limitations, the sulphonamides drugs were arguably more important in
      revolutionising medicine than penicillin, as they achieved the first real success
      in the war against bacteria.

PMID- 21969614
TI  - HVJ liposomes and HVJ envelope vectors.
AB  - This protocol describes techniques for construction of fusion-mediated vectors
      based on inactivated HVJ (hemagglutinating virus of Japan; Sendai virus). HVJ
      liposomes are constructed by fusing liposomes containing DNA with inactivated
      HVJ. The HVJ envelope vector, a more simplified vector, incorporates DNA into
      inactivated HVJ particles without liposomes. Both vectors have many advantages.
      They can be used to introduce proteins, peptides, oligonucleotides (including
      antisense oligonucleotides, decoy oligonucleotides, and ribozymes), and short
      interfering RNA (siRNA), as well as plasmid DNA, into cultured cells in vitro and
      into organs in vivo. Fusion-mediated delivery avoids the degradation of
      therapeutic molecules before reaching the cytoplasm. Finally, repeated injection
      of the vector in vivo is not inhibited and even enhances the effects of the
      delivered molecules. These vectors have been used in many gene therapy
      experiments in animal models to address problems such as liver cirrhosis, hearing
      impairment, ischemic brain damage, peripheral arterial diseases, and cancers.
      This protocol describes methods for the preparation of HVJ liposomes and of HVJ
      envelope vectors and their use in delivery of plasmid DNA into various cells and
      tissues.

PMID- 21969612
TI  - Evolutionary diversification of Mesobuthus alpha-scorpion toxins affecting sodium
      channels.
AB  - alpha-Scorpion toxins constitute a family of peptide modulators that induce a
      prolongation of the action potential of excitable cells by inhibiting voltage
      gated sodium channel inactivation. Although they all adopt a conserved structural
      scaffold, the potency and phylogentic preference of these toxins largely vary,
      which render them an intriguing model for studying evolutionary diversification
      among family members. Here, we report molecular characterization of a new
      multigene family of alpha-toxins comprising 13 members (named MeuNaTxalpha-1 to
      MeuNaTxalpha-13) from the scorpion Mesobuthus eupeus. Of them, five native toxins
      (MeuNaTxalpha-1 to -5) were purified to homogeneity from the venom and the
      solution structure of MeuNaTxalpha-5 was solved by nuclear magnetic resonance. A
      systematic functional evaluation of MeuNaTxalpha-1, -2, -4, and -5 was conducted
      by two-electrode voltage-clamp recordings on seven cloned mammalian voltage-gated
      sodium channels (Na(v)1.2 to Na(v)1.8) and the insect counterpart DmNa(v)1
      expressed in Xenopus oocytes. Results show that all these four peptides slow
      inactivation of DmNa(v)1 and are inactive on Na(v)1.8 at micromolar
      concentrations. However, they exhibit differential specificity for the other six
      channel isoforms (Na(v)1.2 to Na(v)1.7), in which MeuNaTxalpha-4 shows no
      activity on these isoforms and thus represents the first Mesobuthus-derived
      insect-selective alpha-toxin identified so far with a half maximal effective
      concentration of 130 +/- 2 nm on DmNa(v)1 and a half maximal lethal dose of about
      200 pmol g(-1) on the insect Musca domestica; MeuNaTxalpha-2 only affects
      Na(v)1.4; MeuNaTxalpha-1 and MeuNaTxalpha-5 have a wider range of channel
      spectrum, the former active on Na(v)1.2, Na(v)1.3, Na(v)1.6, and Na(v)1.7,
      whereas the latter acting on Na(v)1.3-Na(v)1.7. Remarkably, MeuNaTxalpha-4 and
      MeuNaTxalpha-5 are two nearly identical peptides differing by only one point
      mutation at site 50 (A50V) but exhibit rather different channel subtype
      selectivity, highlighting a switch role of this site in altering the target
      specificity. By the maximum likelihood models of codon substitution, we detected
      nine positively selected sites (PSSs) that could be involved in functional
      diversification of Mesobuthus alpha-toxins. The PSSs include site 50 and other
      seven sites located in functional surfaces of alpha-toxins. This work represents
      the first thorough investigation of evolutionary diversification of alpha-toxins
      derived from a specific scorpion lineage from the perspectives of sequence,
      structure, function, and evolution.

PMID- 21969615
TI  - Immunofluorescence localization of nuclear proteins.
AB  - Many nuclear proteins have been successfully localized using immunofluorescence
      microscopy. These proteins span all nuclear domains, including the nuclear
      envelope, nuclear lamina, nucleolus, chromatin-associated proteins, and proteins
      associated with RNA metabolism and nuclear bodies. This article describes a
      general method for localizing nuclear proteins. Cells grown on coverslips are
      fixed in either formaldehyde or methanol and permeabilized in Triton X-100.
      Incubating the cells with primary antibody and fluorescently conjugated secondary
      antibody allows visualization of the target antigen.

PMID- 21969616
TI  - Methanol-acetone fixation of Drosophila testes.
AB  - This protocol describes two techniques for methanol-acetone fixation of
      Drosophila melanogaster testis squashes. The first method results in very good
      preservation of cell morphology. Fixed cells viewed by phase-contrast optics show
      most of the structural details that can be seen in live material. This allows
      analysis of unstained fixed preparations and selection of the most suitable ones
      for immunostaining. Remarkably, the Y loops, which are usually faint and labile
      in living preparations, become clearly apparent after this type of fixation.
      Moreover, this fixation method results in excellent microtubule preservation for
      immunostaining with antitubulin antibodies. The main disadvantage of this
      technique is poor preservation of chromosome structure. In most instances, the
      chromosomes do not show a distinct morphology and tend to coalesce into one or
      more masses of chromatin. The second technique for methanol-acetone fixation
      described here has proved to be particularly suitable for gamma-tubulin and
      centrosomin immunostaining. It results in preparations having the same
      characteristics as those obtained with the first method.

PMID- 21969617
TI  - Immunostaining of Drosophila testes.
AB  - Fixed Drosophila testis preparations can be immunostained with a variety of
      antibodies. This article describes a general procedure for immunostaining. The
      concentration of the primary antibody will vary with both the type of antibody
      and the type of incubation and should be determined empirically each time.

PMID- 21969618
TI  - Two-photon imaging of neural networks in a mouse model of Alzheimer's disease.
AB  - In humans, Alzheimer's disease (AD) develops over many years. It comprises a
      chain of subtle yet irreversible alterations in brain function, finally leading
      to impairment of memory and cognition. Presymptomatic and thus invisible in
      humans, these alterations can be studied in the animal models of AD. Mouse models
      of the disease expressing AD-related proteins with familial mutations reproduce
      several pathological hallmarks of AD. Although the models do not recapitulate the
      abundant neuronal loss seen in humans, they offer a unique opportunity to learn
      more about synaptic and cellular mechanisms underlying the disease (both in their
      essence and in their temporal sequence) through in vivo analyses of brain
      function. This, however, requires in vivo monitoring of brain function in aged
      living animals at both a single-cell and network level. Tools developed over the
      last several decades can be used to selectively mark and to visualize in vivo
      many important elements of the diseased brain parenchyma, such as amyloid
      plaques, individual neurons, and glial and microglial cells. Here we describe a
      method in which cell-type-specific labeling of neurons and glia is combined with
      in vivo two-photon calcium imaging and fluorescent labeling of amyloid plaques to
      study functional properties of cortical circuits in a mouse model of AD.

PMID- 21969619
TI  - Injection of recombinant adenovirus for delivery of genetically encoded calcium
      indicators into astrocytes of the cerebellar cortex.
AB  - The cerebellar cortex contains two astrocyte types: the Bergmann glia of the
      molecular layer and the velate protoplasmic astrocytes of the granule cell layer.
      In vivo, these cell types generate both subcellular calcium transients and trans
      glial calcium waves. This protocol outlines a method for in vivo calcium imaging
      in cerebellar astrocytes, using the injection of a replication-incompetent
      recombinant adenovirus for gene transfer of the fluorescent calcium indicator
      protein (FCIP) G-CaMP2. The adenovirus contains a cytomegalovirus (CMV) immediate
      early (IE) promoter which confines expression of G-CaMP2 to astrocytes.
      Expression is sufficiently high to allow calcium signals to be recorded in
      Bergmann glial processes as well as the processes and somata of velate
      protoplasmic astrocytes. To obtain structural information, G-CaMP2 fused with the
      brighter chromophore DsRed allows three-dimensional (3D) reconstruction of cells.
      G-CaMP2 expression lasts for at least 3 wk, enabling long-term functional imaging
      in both anesthetized and awake animals.

PMID- 21969620
TI  - Cerebellar craniotomy for in vivo calcium imaging of astrocytes.
AB  - The cerebellar cortex contains two astrocyte types: the Bergmann glia of the
      molecular layer and the velate protoplasmic astrocytes of the granule cell layer.
      In vivo, these cell types generate both subcellular calcium transients and trans
      glial calcium waves. It is possible to perform in vivo calcium imaging in
      cerebellar astrocytes. One method involves injection of a replication-incompetent
      recombinant adenovirus for gene transfer of a fluorescent calcium indicator
      protein. A second method uses multicell bolus loading (MCBL) in the molecular
      layer of the cerebellum with synthetic calcium indicators. This protocol presents
      a cerebellar craniotomy procedure which can be used to prepare a virus-injected
      animal for in vivo imaging. It can also be used to prepare an animal for MCBL.

PMID- 21969621
TI  - Preferential loading of bergmann glia with synthetic acetoxymethyl calcium dyes.
AB  - The cerebellar cortex contains two astrocyte types: the Bergmann glia of the
      molecular layer and the velate protoplasmic astrocytes of the granule cell layer.
      In vivo, these cell types generate both subcellular calcium transients and trans
      glial calcium waves. This protocol outlines a method for in vivo calcium imaging
      in cerebellar astrocytes of mice which have undergone a cerebellar craniotomy.
      Multicell bolus loading (MCBL) is performed using the synthetic calcium
      indicators Fluo-5F AM and Fluo-4 AM. In the cerebellum, a degree of cell-type
      specificity can be achieved by varying the depth of injection. This protocol
      describes a loading procedure following craniotomy which allows preferential
      labeling of Bergmann glia.

PMID- 21969622
TI  - Digital scanned laser light-sheet fluorescence microscopy (DSLM) of zebrafish and
      Drosophila embryonic development.
AB  - Embryonic development is one of the most complex processes encountered in
      biology. In vertebrates and higher invertebrates, a single cell transforms into a
      fully functional organism comprising several tens of thousands of cells, arranged
      in tissues and organs that perform impressive tasks. In vivo observation of this
      biological process at high spatiotemporal resolution and over long periods of
      time is crucial for quantitative developmental biology. Importantly, such
      recordings must be realized without compromising the physiological development of
      the specimen. In digital scanned laser light-sheet fluorescence microscopy
      (DSLM), a specimen is rapidly scanned with a thin sheet of light while
      fluorescence is recorded perpendicular to the axis of illumination with a camera.
      Combining light-sheet technology and fast laser scanning, DSLM delivers
      quantitative data for entire embryos at high spatiotemporal resolution. Compared
      with confocal and two-photon fluorescence microscopy, DSLM exposes the embryo to
      at least three orders of magnitude less light energy, but still provides up to 50
      times faster imaging speeds and a 10-100-fold higher signal-to-noise ratio. By
      using automated image processing algorithms, DSLM images of embryogenesis can be
      converted into a digital representation. These digital embryos permit following
      cells as a function of time, revealing cell fate as well as cell origin. By means
      of such analyses, developmental building plans of tissues and organs can be
      determined in a whole-embryo context. This article presents a sample preparation
      and imaging protocol for studying the development of whole zebrafish and
      Drosophila embryos using DSLM.

PMID- 21969623
TI  - Time-lapse imaging of live Phallusia embryos for creating 3D digital replicas.
AB  - During embryonic development, cell behaviors that are tightly coordinated both
      spatially and temporally integrate at the tissue level and drive embryonic
      morphogenesis. Over the past 20 years, advances in imaging techniques, in
      particular, the development of confocal imaging, have opened a new world in
      biology, not only giving us access to a wealth of information, but also creating
      new challenges. It is sometimes difficult to make the best use of the recordings
      of the complex, inherently three-dimensional (3D) processes we now can observe.
      In particular, these data are often not directly suitable for even simple but
      conceptually fundamental quantifications. This article provides a method to
      fluorescently label and image structures of interest that will subsequently be
      reconstructed, such as cell membranes or nuclei. The protocol describes live
      imaging of Phallusia mammillata embryos, which are robust, colorless, and
      optically transparent with negligible autofluorescence. Their diameter ranges
      from 100 um to 120 um, which allows time-lapse microscopy of whole embryos using
      two-photon microscopy with a high-resolution objective. Although two-photon
      imaging is described in detail, any imaging technology that results in a z-stack
      may be used. The resulting image stacks can subsequently be digitalized and
      segmented to produce 3D embryo replicas that can be interfaced to a model
      organism database and used to quantify cell shapes.

PMID- 21969624
TI  - Imaging of fixed ciona embryos for creating 3D digital replicas.
AB  - During embryonic development, cell behaviors that are tightly coordinated both
      spatially and temporally integrate at the tissue level and drive embryonic
      morphogenesis. Over the past 20 years, advances in imaging techniques, in
      particular, the development of confocal imaging, have opened a new world in
      biology, not only giving us access to a wealth of information, but also creating
      new challenges. It is sometimes difficult to make the best use of the recordings
      of the complex, inherently three-dimensional (3D) processes we now can observe.
      In particular, these data are often not directly suitable for even simple but
      conceptually fundamental quantifications. This article presents a method for
      imaging embryonic development with cellular resolution in fixed ascidian embryos.
      A large fraction of the ascidian community primarily studies the development of
      the cosmopolitan ascidian Ciona intestinalis. Because the embryos of this species
      are insufficiently transparent and show significant autofluorescence, live
      imaging is difficult. Thus, whole embryos are fixed and optically cleared. They
      are then stained and imaged on a regular or two-photon confocal microscope. The
      resulting image stacks can subsequently be digitalized and segmented to produce
      3D embryo replicas that can be interfaced to a model organism database and used
      to quantify cell shapes.

PMID- 21969625
TI  - Creating 3D digital replicas of ascidian embryos from stacks of confocal images.
AB  - During embryonic development, cell behaviors that are tightly coordinated both
      spatially and temporally integrate at the tissue level and drive embryonic
      morphogenesis. Over the past 20 years, advances in imaging techniques, in
      particular, the development of confocal imaging, have opened a new world in
      biology, not only giving us access to a wealth of information, but also creating
      new challenges. It is sometimes difficult to make the best use of the recordings
      of the complex, inherently three-dimensional (3D) processes we now can observe.
      In particular, these data are often not directly suitable for even simple but
      conceptually fundamental quantifications. This article describes a process
      whereby image stacks gathered from live or fixed ascidian embryos are digitalized
      and segmented to produce 3D embryo replicas. These replicas can then be
      interfaced via a 3D Virtual Embryo module to a model organism database (Aniseed)
      that allows one to relate the geometrical properties of cells and cell contacts
      to additional parameters such as cell lineage, cell fates, or the underlying
      genetic program. Such an integrated system can serve several general purposes.
      First, it makes it possible to quantify and better understand the dynamics of
      cell behaviors during embryonic development, including, for instance, the
      automatic detection of asymmetric cell divisions or the evolution of cell
      contacts. Second, the 3D Virtual Embryo software proposes a panel of mathematical
      shape descriptors to precisely quantify cellular geometries and generate a 3D
      identity card for each embryonic cell. Such reconstructions open the door to a
      detailed 3D simulation of morphogenesis.

PMID- 21969626
TI  - "Statistics 101"--a primer for the genetics of complex human disease.
AB  - This article reviews the basis of probability and statistics used in the genetic
      analysis of complex human diseases and illustrates their use in several simple
      examples. Much of the material presented here is so fundamental to statistics
      that it has become common knowledge in the field and the originators are no
      longer cited (e.g., Gauss).

PMID- 21969627
TI  - An assay for visual learning in individual Drosophila larvae.
AB  - Vision is a major sensory modality in Drosophila behavior, with more than one
      half of the Drosophila brain devoted to visual processing. The mechanisms of
      vision in Drosophila can now be studied in individuals and in populations of
      flies by using various paradigms. Simple strategies for conducting visual
      perception and learning studies consist of individual studies performed on single
      flies on solid supports (larvae on agar or adults in a T-maze) using a light/dark
      association paradigm. These approaches are quite easy to implement but are fairly
      limited in their ability to address questions of visual perception. Nevertheless,
      the simpler approaches treating vision in one dimension (light, dark) do provide
      effective paradigms for genetic analysis. This article describes a protocol for
      larval visual learning. Larvae are transferred back and forth between well-lit or
      dark agarose plates that either do or do not contain fructose (which is
      appetitive) as the unconditioned stimulus (US). Such appetitive larval visual
      memory is tested by tallying the time spent in light or dark quadrants of a plate
      (without a US).

PMID- 21969628
TI  - The aversive phototaxic suppression assay for individual adult Drosophila.
AB  - Vision is a major sensory modality in Drosophila behavior, with more than one
      half of the Drosophila brain devoted to visual processing. The mechanisms of
      vision in Drosophila can now be studied in individuals and in populations of
      flies by using various paradigms. Simple strategies for conducting visual
      perception and learning studies consist of individual studies performed on single
      flies on solid supports (larvae on agar or adults in a T-maze) using a light/dark
      association paradigm. These approaches are quite easy to implement but are fairly
      limited in their ability to address questions of visual perception. Nevertheless,
      the simpler approaches treating vision in one dimension (light, dark) do provide
      effective paradigms for genetic analysis. For adult flies, a paradigm called
      aversive phototaxic suppression (APS), as described here, can be used. This
      method exploits flies' phototaxic reflex. By associating a lit chamber with
      quinine (which is aversive), repeated trials on a single animal result in a
      learned response to avoid (or to suppress) phototaxis. Of note, the unconditioned
      stimulus (US) quinine must be present throughout the experiment for APS to work,
      unlike other memory assays in which the US is removed during testing.

PMID- 21969630
TI  - The in vivo invasion assay: preparation and handling of collection needles.
AB  - Analysis of the individual steps in metastasis is crucial if insights at the
      molecular level are to be linked to the cell biology of cancer. A technical
      hurdle to achieving the analysis of the individual steps of metastasis is the
      fact that, at the gross level, tumors are heterogeneous in both animal models and
      patients. Human primary tumors show extensive variation in all properties ranging
      from growth and morphology of the tumor through tumor-cell density in the blood
      and formation and growth of metastases. Methods capable of the direct
      visualization and analysis of tumor-cell behavior at single-cell resolution in
      vivo have become crucial in advancing the understanding of mechanisms of
      metastasis, the definition of microenvironment, and the markers related to both.
      High-resolution multiphoton imaging of tumors in vivo is a valuable tool in this
      regard. Because tumor cells have been found to be attracted to blood vessels, the
      in vivo invasion assay was developed to analyze which factors may stimulate
      invasion of these cells into the vessels. This protocol describes the preparation
      and handling of collection needles for the assay. A set of 33-gauge needles is
      used to create artificial or surrogate blood vessels that are injected into
      tumors, using a special holding device attached to a micromanipulator to
      stabilize the needle positions during and after insertion into the anesthetized
      animal. The needles are filled with Matrigel and various growth factors to
      determine which of these factors may influence the invading tumor cells.

PMID- 21969629
TI  - High-resolution multiphoton imaging of tumors in vivo.
AB  - Analysis of the individual steps in metastasis is crucial if insights at the
      molecular level are to be linked to the cell biology of cancer. A technical
      hurdle to achieving the analysis of the individual steps of metastasis is the
      fact that, at the gross level, tumors are heterogeneous in both animal models and
      patients. Human primary tumors show extensive variation in all properties ranging
      from growth and morphology of the tumor through tumor-cell density in the blood
      and formation and growth of metastases. Methods capable of the direct
      visualization and analysis of tumor-cell behavior at single-cell resolution in
      vivo have become crucial in advancing the understanding of mechanisms of
      metastasis, the definition of microenvironment, and the markers related to both.
      This article discusses the use of high-resolution multiphoton imaging of tumors
      (specifically breast tumors in mice) in vivo.

PMID- 21969631
TI  - First steps for fluorescence correlation spectroscopy of living cells.
AB  - Fluorescence correlation spectroscopy (FCS) has become a powerful and sensitive
      tool in biochemistry and biophysics. It directly obtains physical parameters such
      as the average number of fluorescent molecules and their diffusion time in a tiny
      detection area. It also provides other useful information such as the brightness
      of molecules. Ultimately, it can give precise information about molecular
      interactions in the aqueous condition. This article outlines the basic parameters
      and properties of FCS.

PMID- 21969633
TI  - Fluorescence correlation spectroscopy example: shift of autocorrelation curve.
AB  - Fluorescence correlation spectroscopy (FCS) has become a powerful and sensitive
      tool in biochemistry and biophysics. It directly obtains physical parameters such
      as the average number of fluorescent molecules and their diffusion time in a tiny
      detection area. It also provides other useful information such as the brightness
      of molecules. Ultimately, it can give precise information about molecular
      interactions in the aqueous condition. In FCS experiments, the fluctuation of
      fluorescence emission intensity from the tiny detection area is monitored as a
      function of time. The monitored fluorescence fluctuation signals are transformed
      to an autocorrelation curve according to the autocorrelation calculator unit and
      the curves are then fitted to an appropriate physical model. This protocol
      outlines an FCS example involving a shift of the autocorrelation curve.

PMID- 21969632
TI  - Basic fluorescence correlation spectroscopy setup and measurement.
AB  - Fluorescence correlation spectroscopy (FCS) has become a powerful and sensitive
      tool in biochemistry and biophysics. It directly obtains physical parameters such
      as the average number of fluorescent molecules and their diffusion time in a tiny
      detection area. It also provides other useful information such as the brightness
      of molecules. Ultimately, it can give precise information about molecular
      interactions in the aqueous condition. This protocol outlines the basic FCS setup
      and how measurements are made.

PMID- 21969634
TI  - Prison overcrowding in the context of the ACA.

PMID- 21969635
TI  - Lost in the crowd: prison mental health care, overcrowding, and the courts.
AB  - Skyrocketing inmate populations have put considerable pressure on prison mental
      health services. In California, prison populations have exceeded 200% of
      capacity, and litigation to rectify constitutionally inadequate care has been
      under way for more than two decades. After the failure of other remedies, a
      federal court ordered the state to reduce its inmate population to 137.5% of
      capacity in two years. The U.S. Supreme Court upheld the order, although it
      signaled that California could obtain more time to comply. Other states now are
      on notice that the justices will not permit grossly inadequate treatment
      conditions to continue indefinitely.

PMID- 21969636
TI  - Long-term impact of web-based tools, leadership feedback, and policies on
      inpatient antipsychotic polypharmacy.
AB  - This column describes a series of interventions to decrease antipsychotic
      polypharmacy in the New York State Office of Mental Health (NYSOMH) network of
      psychiatric hospitals. Phase 1 consisted of implementation of the Psychiatric
      Services Clinical Knowledge Enhancement System (PSYCKES), a Web-based application
      supporting clinical decision making and quality improvement, and a policy
      requiring approval by NYSOMH's medical director to prescribe more than two
      antipsychotics per patient. In phase 2 hospital leaders received feedback from
      the office of the medical director identifying specific patients on polypharmacy.
      In phase 3, access to PSYCKES continued, but the prior-approval policy and
      feedback were discontinued. Polypharmacy decreased significantly during phase 1,
      from 16.9 to 9.7 inpatients per 1,000, and decreased further in phase 2, to 3.9
      inpatients per 1,000. In phase 3 the prevalence of antipsychotic polypharmacy
      remained low at six-month follow-up (3.1 inpatients per 1,000), despite the
      ending of state-level oversight. On long-term follow-up, polypharmacy increased,
      eventually rising to 9.2 inpatients per 1,000 after 36 months, but remained well
      below baseline levels.

PMID- 21969637
TI  - Resilience: message from a "Mengele Twin" survivor.

PMID- 21969638
TI  - Uninsurance among nonelderly adults with and without frequent mental and physical
      distress in the United States.
AB  - OBJECTIVES: This research describes uninsurance rates over time among nonelderly
      adults in the United States with or without frequent physical and mental distress
      and provides estimates of uninsurance by frequent mental distress status and
      sociodemographic characteristics nationally and by state. METHODS: Data from the
      1993 through 2009 Behavioral Risk Factor Surveillance System, a telephone survey
      that uses random-digit dialing, were used to examine the prevalence of
      uninsurance among nearly 3 million respondents by self-report of frequent
      physical and frequent mental distress and sociodemographic characteristics,
      response year, and state of residence. RESULTS: After adjustment for
      sociodemographic characteristics, uninsurance among adults aged 18 to 64 years
      was markedly higher among those with frequent mental distress only (22.6%) and
      those with both frequent mental and frequent physical distress (21.8%) than among
      those with frequent physical distress only (17.7%). The prevalence of uninsurance
      did not differ markedly between those with only frequent mental distress and
      those with both frequent mental distress and frequent physical distress. The
      prevalence of uninsurance among those with frequent mental distress only and
      those with neither frequent mental distress nor frequent physical distress
      increased significantly over time. CONCLUSIONS: Uninsurance rates among
      nonelderly adults with frequent mental distress were disproportionately high. The
      results of this analysis can be used as baseline data to assess whether
      implementation of the Affordable Care Act is accompanied by changes in health
      care access, utilization, and self-reported measures of health, particularly
      among those with mental illness.

PMID- 21969639
TI  - Predicting psychiatric hospital admission among adults with schizophrenia.
AB  - OBJECTIVE: The authors identified patient characteristics that increased risk of
      hospital admission among adults with schizophrenia. METHODS: A total of 1,460
      participants in the Clinical Antipsychotic Trials of Intervention Effectiveness
      (CATIE) clinical trial were followed from the time they began a randomized trial
      of medication to first schizophrenia-related hospital admission. RESULTS: In 869
      person-years of follow-up, 203 patients were hospitalized. Increased risk of
      hospital admission was associated with early age (<= 17 years) of first
      antipsychotic treatment (adjusted hazard ratio [AHR]=2.16, 95% confidence
      interval [CI]=1.49-3.11), psychiatric hospitalization in past year (AHR=2.99,
      CI=2.23-4.00), having had DSM-IV alcohol (AHR=1.56, CI=1.16-2.10) or drug
      (AHR=1.50, CI=1.13-2.00) use disorders in the past five years, and baseline
      severe symptoms according to the Clinical Global Impressions Scale (AHR=1.54,
      CI=1.04-2.27), presence of tardive dyskinesia (AHR=1.55, CI=1.07-2.23), a high
      score on the positive symptoms subscale of the Positive and Negative Syndrome
      Scale (AHR=1.52, CI=1.07-2.15), and low social function (AHR=1.45, CI=1.03-2.04).
      As compared with olanzapine, the drugs quetiapine (AHR=2.14, CI=1.39-3.31),
      perphenazine (AHR=1.80, CI=1.11-2.94), and ziprasidone (AHR=2.70, CI=1.64-4.44)
      were associated with increased hospitalization risk. Risperidone was associated
      with a lower hospitalization risk than quetiapine (AHR=1.50, CI=1.01-2.22) and
      ziprasidone (AHR=1.89, CI=1.19-3.01). CONCLUSIONS: Efforts to lower hospital
      admission risk among individuals with schizophrenia should focus on history of
      early onset, recent inpatient admission, severe positive symptoms, poor social
      function, high global illness severity, and comorbid substance use disorders and
      on selection of an appropriate antipsychotic medication.

PMID- 21969640
TI  - Service use among patients with serious mental illnesses who presented with
      physical symptoms at intake.
AB  - OBJECTIVE: The goal of this study was to examine relationships among serious
      mental illness, general physical symptoms, and use of mental health services
      among persons presenting for admission at a community-based mental health center.
      METHODS: Number and type of physical symptoms were assessed during the routine
      intake process. Individuals (N=1,022) were screened by phone with a modified
      version of the Physical Health Questionnaire-15. Diagnostic, demographic, and
      treatment information was tracked prospectively. Data were analyzed for 682
      individuals who kept at least one appointment. Analyses examined associations
      among physical symptoms, diagnosis, and service use over time. RESULTS: A total
      of 481 patients (71%) reported three or more physical symptoms. Patients with
      three or more physical symptoms were significantly older (p<.013), were more
      likely to be female (p<.001) and Spanish speaking (p<.05), and used significantly
      more services (p<.001) than did those with fewer physical symptoms. Both the
      number and the costs of services increased with the number of physical symptoms
      presented at intake. Patients with major depressive disorder were as likely as
      patients with schizophrenia or bipolar disorder to report having three or more
      physical symptoms. CONCLUSIONS: Within a mental health community-based
      population, most incoming clients with serious mental illness reported three or
      more physical symptoms. The number of reported physical symptoms was a
      significant predictor of mental health service use and cost over the episode of
      care, even after analyses controlled for confounders such as gender, age, and
      diagnosis.

PMID- 21969641
TI  - Psychiatric and general medical conditions comorbid with bipolar disorder in the
      National Hospital Discharge Survey.
AB  - OBJECTIVE: From 40% to 65% of patients with bipolar disorder are estimated to
      have diagnoses of one or more comorbid conditions. The purpose of this study was
      to identify comorbid disorders and compare their prevalence in hospitalizations
      of persons with or without bipolar disorder. METHODS: Data from the 1979-2006
      National Hospital Discharge Survey (NHDS) were analyzed to examine temporal
      trends in the proportional morbidity of bipolar disorder, demographic
      characteristics, and the most frequent comorbid conditions in hospitalizations of
      patients with or without bipolar disorder. Among discharges of patients ages 13
      64, the conditions of those with a primary diagnosis of bipolar disorder
      (N=27,054) were compared with those with other primary diagnoses (N=2,325,247).
      Proportional morbidity ratios (PMRs) were calculated. RESULTS: There was an
      average 10% (p<.001) increase per year in the proportion of discharges with
      bipolar disorder. Proportions of discharge records that noted bipolar disorder
      were higher among females and whites and were highest among persons ages 13-19
      and those from the Northeast. Discharge records noting a primary diagnosis of
      bipolar disorder showed higher proportions of most psychiatric and some general
      medical conditions, including acquired hypothyroidism (proportional morbidity
      ratio=2.6), viral hepatitis (1.6), obesity (1.4), and various diseases of the
      skin and subcutaneous tissue (range 2.6-4.2) and of the nervous (1.4-3.8),
      respiratory (1.4-2.3), and musculoskeletal (1.2-1.9) systems. CONCLUSIONS:
      Patients with bipolar disorder have an increased illness burden from many
      psychiatric and general medical conditions. Knowledge of the most prevalent
      comorbid conditions and methods for their prevention, early diagnosis, and
      treatment are critical in improving the prognosis of patients with bipolar
      disorder.

PMID- 21969642
TI  - Medicare beneficiaries with depression: comparing diagnoses in claims data with
      the results of screening.
AB  - OBJECTIVE: The study evaluated the accuracy of Medicare claims in identifying
      elderly patients with depression compared with diagnoses of depression made with
      validated self-report depression scales. METHODS: The study included 1,551
      participants in the Medicare Primary and Consumer-Directed Care Demonstration.
      They resided in 19 counties in three states. Depression diagnoses made by two
      validated self-rated scales- the Mini-International Neuropsychiatric Interview
      Major Depressive Episode Module (MINI-MDE) and the 15-item Geriatric Depression
      Scale (GDS) were compared with depression identified diagnoses listed in Medicare
      claims. The main outcome measures were the sensitivity, specificity, and positive
      and negative predictive values for ICD-9-CM depression codes included in Medicare
      claims. For validation, two-year periods and additional diagnostic codes were
      also considered. RESULTS: Compared with the MINI-MDE or GDS, the sensitivity and
      positive predictive values for Medicare claims were below 50%, and specificity
      and negative predictive values were over 70%. CONCLUSIONS: The study demonstrated
      the predictive power and limitations of using administrative claims data for
      identifying patients with depression in the Medicare population. Using Medicare
      claims to identify patients with depression may lead to underestimation of
      depression prevalence and may compromise researchers' ability to examine issues
      related to quality, costs, and utilization.

PMID- 21969643
TI  - Effects of race and ethnicity on depression treatment outcomes: the CO-MED trial.
AB  - OBJECTIVE: The investigators examined whether outcomes differ by race-ethnicity
      for patients with major depressive disorder in acute- (12 weeks) and continuation
      phase (weeks 12-28) treatment with one of two antidepressant combinations or one
      selective serotonin reuptake inhibitor. METHODS: This single-blind, seven-month
      prospective, randomized trial enrolled 352 non-Hispanic white (59%), 169 black
      (28%), and 79 white Hispanic (13%) participants from six primary and nine
      psychiatric care U.S. sites. Patients had nonpsychotic chronic or recurrent major
      depressive disorder (or both) of at least moderate severity. Escitalopram plus
      placebo, bupropion sustained-release plus escitalopram, or venlafaxine extended
      release plus mirtazapine were delivered according to measurement-based care. The
      primary outcome was remission (last two consecutive 16-item Quick Inventory of
      Depressive Symptomatology-Self-Report ratings <8 and <6); secondary outcomes
      included side effects, adverse events, quality of life, function, and attrition.
      RESULTS: Black participants had greater baseline psychiatric and medical
      comorbidity. Baseline depression severity did not significantly differ between
      groups. In both phases more blacks than those in other groups exited the trial
      early. There were only minor differences in side effects, no significant
      differences in remission rates, and no significant differences between groups in
      other outcomes for each treatment. CONCLUSIONS: Despite differences in
      sociodemographic characteristics and comorbidities, when measurement-based care
      was used, members of different minority groups had similar outcomes when treated
      with one antidepressant or a combination of two antidepressants. Black
      participants had the highest attrition rate, an important issue to address in
      clinical care.

PMID- 21969644
TI  - Mental health service use by persons of Asian ancestry with DSM-IV mental
      disorders in the United States.
AB  - OBJECTIVES: This study compared the prevalence and odds of mental health service
      utilization among people of Asian ancestry with lifetime DSM-IV mood, anxiety,
      alcohol, and drug use disorders with utilization by members of other racial and
      ethnic groups with similar disorders. METHODS: Between 2001 and 2002, a total of
      43,093 noninstitutionalized individuals were assessed by the National
      Epidemiologic Survey on Alcohol and Related Conditions (NESARC) study of lifetime
      prevalence of DSM-IV psychiatric disorders and mental health service utilization
      among various ethnic and racial groups. RESULTS: Among individuals with lifetime
      mood disorders, Asians had significantly lower mental health service utilization
      compared with whites (odds ratio [OR]=.31, 95% confidence interval [CI]=.21-.46),
      Hispanics (OR=.49, CI=.33-71), and Native Americans (OR=.27, CI=.15-.48) but
      similar utilization compared with blacks. There were no statistically significant
      differences in lifetime mental health service utilization for alcohol and drug
      use disorders among racial and ethnic groups. CONCLUSIONS: Asians with lifetime
      mood disorders underutilized mental health services even after adjustment was
      made for socioeconomic variables and years of residency in the United States.
      Future studies of culture-specific attitudes, correlates, and barriers to mental
      health service utilization are warranted.

PMID- 21969645
TI  - Symptoms of schizophrenia and psychosis according to foreign birth in a Canadian
      sample of homeless persons.
AB  - OBJECTIVE: The objective of the study was to examine the relationship between
      foreign birth and symptoms of schizophrenia and psychosis in a clinical sample of
      homeless persons. METHODS: All the charts documented between 2002 and 2007 by a
      psychiatric outreach team in Ottawa, Canada, were retrospectively reviewed
      regarding country of birth and psychiatric symptoms identified in a clinical
      assessment. Data were analyzed by univariate and multivariate logistic
      regressions. RESULTS: The sample included 552 men and 333 women with data on
      psychiatric symptoms and country of birth. A total of 106 individuals (12%) were
      born outside of Canada. This proportion was lower than that observed in the
      general population of Ottawa or in Canada. Foreign-born individuals were older
      and had a higher level of education than Canadian-born individuals. Sixteen
      percent of the sample presented symptoms of schizophrenia, and 15% presented
      symptoms of psychosis other than schizophrenia. In univariate analyses persons
      presenting symptoms of schizophrenia or psychosis were more likely to be foreign
      born than native-born (odds ratio [OR]=2.92, 95% confidence interval [CI]=1.74
      4.90, and OR=4.79, CI=2.92-7.86, respectively). Multivariate analyses gave very
      similar results (OR=2.62, CI=1.50-4.58, and OR=4.14, CI=2.44-7.03, respectively).
      A positive trend or significant association was observed for all regions of
      origin other than the non-Caribbean Americas. CONCLUSIONS: This is the first
      study to report an association between foreign birth and symptoms of
      schizophrenia and psychosis among homeless persons. These findings are consistent
      with the increased risk of schizophrenia and psychosis observed among immigrants
      to European countries.

PMID- 21969647
TI  - Untreated posttraumatic stress among persons with severe mental illness despite
      marked trauma and symptomatology.
AB  - OBJECTIVE: The study examined the degree to which trauma was addressed among
      clients being treated for a severe mental illness and a substance use disorder at
      a community mental health center. METHODS: Participants (N=74) were a randomly
      selected sample of clients who were enrolled for at least two years in an
      outpatient clinic and who had at least one clinic visit in the month preceding
      the study's start. The primary diagnoses were schizophrenia or schizoaffective
      disorder (53%), bipolar disorder (24%), and major depression (23%), and all
      participants had a current or past substance use disorder. A majority had a
      history of trauma, including sexual trauma, physical assault, the loss of a
      family member, or having witnessed someone being killed or seriously injured.
      RESULTS: Clients were asked about past sexual or physical assault history by a
      median of zero providers, and 59% said a history of assault was not addressed
      during treatment. Severity of posttraumatic stress disorder and the range of
      traumas experienced by the client were not predictors of the degree to which
      trauma and its consequences were a part of treatment. Clients' desire to discuss
      trauma during treatment and feeling upset while discussing trauma were both
      predictors of whether trauma was a focus of treatment. CONCLUSIONS: Clinicians
      may not adequately address trauma during treatment of severe mental illness.
      Future research is required to examine more effective methods to screen and treat
      trauma among individuals with severe mental illnesses.

PMID- 21969646
TI  - Continuing care and long-term substance use outcomes in managed care: early
      evidence for a primary care-based model.
AB  - OBJECTIVES: How best to provide ongoing services to patients with substance use
      disorders to sustain long-term recovery is a significant clinical and policy
      question that has not been adequately addressed. Analyzing nine years of
      prospective data for 991 adults who entered substance abuse treatment in a
      private, nonprofit managed care health plan, this study aimed to examine the
      components of a continuing care model (primary care, specialty substance abuse
      treatment, and psychiatric services) and their combined effect on outcomes over
      nine years after treatment entry. METHODS: In a longitudinal observational study,
      follow-up measures included self-reported alcohol and drug use, Addiction
      Severity Index scores, and service utilization data extracted from the health
      plan databases. Remission, defined as abstinence or nonproblematic use, was the
      outcome measure. RESULTS: A mixed-effects logistic random intercept model
      controlling for time and other covariates found that yearly primary care, and
      specialty care based on need as measured at the prior time point, were positively
      associated with remission over time. Persons receiving continuing care (defined
      as having yearly primary care and specialty substance abuse treatment and
      psychiatric services when needed) had twice the odds of achieving remission at
      follow-ups (p<.001) as those without. CONCLUSIONS: Continuing care that included
      both primary care and specialty care management to support ongoing monitoring,
      self-care, and treatment as needed was important for long-term recovery of
      patients with substance use disorders.

PMID- 21969648
TI  - After the black box warning: predictors of psychotropic treatment choices for
      older patients with dementia.
AB  - OBJECTIVES: This study aimed to evaluate factors associated with the selection of
      pharmacological treatments often given as first-line treatments to elderly
      patients with neuropsychiatric symptoms associated with dementia. It also
      evaluated patterns of medication usage over time in the year preceding and three
      years after the U.S. Food and Drug Administration issued a black box warning for
      antipsychotic usage. METHODS: A retrospective cohort consisted of 19,517 Veterans
      Affairs patients with diagnosed dementia and a new outpatient start with an
      antipsychotic agent (haloperidol, olanzapine, quetiapine, or risperidone) or
      valproic acid and its derivatives between May 1, 2004, and September 30, 2008.
      Patient and facility characteristics were examined for their association with the
      new starts of these medications. RESULTS: Trends in the rate of fills for
      psychotropic medications varied, with yearly increases in the use of quetiapine,
      haloperidol, and valproic acid and decreasing use of olanzapine and risperidone.
      Predictors of haloperidol use included a new start in nonpsychiatric settings,
      prior benzodiazepine use, and any prior-year hospitalization. Anxiety disorder
      and major depression were predictive of not receiving haloperidol. Parkinson's
      disease was predictive of quetiapine use, whereas bipolar disorder was predictive
      of valproic acid use. Older age was predictive of use of antipsychotics rather
      than valproic acid. Urban facilities were less likely to use olanzapine, and
      significant regional variations were seen. CONCLUSIONS: Important patient and
      facility characteristics were associated with initiating different psychotropic
      agents among elderly dementia patients. In addition, the rate of use and the
      factors predictive of use varied across the study years.

PMID- 21969649
TI  - Requiring case management meetings to be conducted outside the clinic.
AB  - In this Open Forum a psychiatric health care consumer recounts his experience
      with his state's requirement to hold case management meetings outside of the
      clinic. Over time, the author found that meeting elsewhere amounted to being put
      on public display, and he felt embarrassed and powerless to change the situation.
      Requiring people with psychiatric disorders to meet outside a clinical setting
      may violate the Health Insurance Portability and Accountability Act and human
      rights. This New Hampshire state policy needs to be changed because it undermines
      treatment and reinforces the stigma that many consumers already feel because of
      their disability.

PMID- 21969650
TI  - "How to speak to your psychiatrist": shared decision-making training for
      inpatients with schizophrenia.
AB  - OBJECTIVE: Involving patients with mental illness in shared decision making about
      their treatment has recently attracted attention, but existing interventions may
      insufficiently motivate or enable patients with schizophrenia to behave more
      actively. This study evaluated a new intervention. METHODS: In a pilot study 61
      inpatients with schizophrenia or schizoaffective disorder from a psychiatric
      hospital in Germany were randomly assigned to receive shared decision-making
      training (N=32) or cognitive training (N=29, control condition). RESULTS: The
      shared decision-making training yielded higher participation preferences and
      increased patients' desire to have more responsibility in treatment decisions,
      which continued to the six-month follow-up. Patients in the intervention group
      became more skeptical of treatment and were perceived as more "difficult" by
      their psychiatrists. CONCLUSIONS: Training in shared decision making was highly
      accepted by patients and changed attitudes toward participation in decision
      making. There were some hints that it might generate beneficial long-term
      effects.

PMID- 21969651
TI  - Religiosity among adults who are chronically homeless: association with clinical
      and psychosocial outcomes.
AB  - OBJECTIVE: This study examined changes in religious faith among homeless people
      enrolled in a supported housing program and their association with clinical and
      psychosocial outcomes. METHODS: A total of 582 clients at 11 sites were separated
      into three groups based on whether they reported a decrease, an increase, or no
      change in their religiosity scores at one-year follow-up. Groups were compared on
      outcomes controlled for baseline measures. RESULTS: At one-year follow-up,
      participants who gained faith reported doing more volunteer work, being more
      engaged in community activities, and having a higher quality of life than those
      who lost faith. Participants who reported a large gain in faith had better mental
      health ratings than those who reported a large loss in faith. CONCLUSIONS:
      Religious faith is a correlate of improvement among chronically homeless adults
      and may influence clinical and psychosocial outcomes.

PMID- 21969652
TI  - Underutilization of mental health services among bereaved caregivers with
      prolonged grief disorder.
AB  - OBJECTIVE: This study examined grief and mental health service use among 86
      bereaved caregivers of advanced cancer patients. METHODS: Caregivers were
      assessed before (median=3.1 months) and after (median=6.6 months) patients'
      deaths for prolonged grief disorder, axis I psychiatric disorders, mental health
      service use, suicidality, and health-related quality of life. RESULTS: Sixteen
      percent of the bereaved sample met criteria for prolonged grief disorder, which
      was significantly associated with suicidality and poorer health-related quality
      of life, but not with mental health service use. The majority of bereaved
      caregivers with prolonged grief disorder did not access mental health services.
      In multivariable analyses, having discussed psychological concerns with a health
      care professional when the patient was ill was the only significant predictor of
      mental health service use during bereavement. CONCLUSIONS: Because bereaved
      caregivers with prolonged grief disorder underutilize mental health services,
      connecting them with services while the patient is still alive may be beneficial.

PMID- 21969653
TI  - Trajectories in use of substance abuse and mental health services among stimulant
      users in rural areas.
AB  - OBJECTIVE: This study examined substance abuse and mental health service
      utilization during a three-year period among stimulant users living in rural
      areas. METHODS: Participants (N=710) were interviewed at baseline and every six
      months for 36 months. One-step transition probabilities were constructed between
      the two types of service use for each consecutive pair of interviews to examine
      the resulting steady-state probabilities among multiple one-step transition
      matrices. RESULTS: Most participants received no substance abuse or mental health
      services. On average, the probabilities of reporting use of the same types of
      services during the 36-month follow-up were 82% for receiving neither service, 9%
      for receiving only mental health treatment, 6% for receiving only substance abuse
      treatment, and 2% for receiving both services. CONCLUSIONS: Further study is
      needed to determine factors that affect the decision to seek mental health or
      substance abuse treatment among residents of rural communities.

PMID- 21969654
TI  - A misused term.

PMID- 21969655
TI  - Assessing the career satisfaction of psychiatrists.

PMID- 21969657
TI  - Psychosis and homicide.

PMID- 21969659
TI  - Incentives to reduce metabolic side effects of antipsychotics.

PMID- 21969661
TI  - RADIANCE: An automated, enterprise-wide solution for archiving and reporting CT
      radiation dose estimates.
AB  - There is growing interest in the ability to monitor, track, and report exposure
      to radiation from medical imaging. Historically, however, dose information has
      been stored on an image-based dose sheet, an arrangement that precludes
      widespread indexing. Although scanner manufacturers are beginning to include dose
      related parameters in the Digital Imaging and Communications in Medicine (DICOM)
      headers of imaging studies, there remains a vast repository of retrospective
      computed tomographic (CT) data with image-based dose sheets. Consequently, it is
      difficult for imaging centers to monitor their dose estimates or participate in
      the American College of Radiology (ACR) Dose Index Registry. An automated
      extraction software pipeline known as Radiation Dose Intelligent Analytics for CT
      Examinations (RADIANCE) has been designed that quickly and accurately parses CT
      dose sheets to extract and archive dose-related parameters. Optical character
      recognition of information in the dose sheet leads to creation of a text file,
      which along with the DICOM study header is parsed to extract dose-related data.
      The data are then stored in a relational database that can be queried for dose
      monitoring and report creation. RADIANCE allows efficient dose analysis of CT
      examinations and more effective education of technologists, radiologists, and
      referring physicians regarding patient exposure to radiation at CT. RADIANCE also
      allows compliance with the ACR's dose reporting guidelines and greater awareness
      of patient radiation dose, ultimately resulting in improved patient care and
      treatment.

PMID- 21969662
TI  - Quality initiatives: CT radiation dose reduction: how to implement change without
      sacrificing diagnostic quality.
AB  - The risks and benefits of using computed tomography (CT) as opposed to another
      imaging modality to accomplish a particular clinical goal should be weighed
      carefully. To accurately assess radiation risks and keep radiation doses as low
      as reasonably achievable, radiologists must be knowledgeable about the doses
      delivered during various types of CT studies performed at their institutions. The
      authors of this article propose a process improvement approach that includes the
      estimation of effective radiation dose levels, formulation of dose reduction
      goals, modification of acquisition protocols, assessment of effects on image
      quality, and implementation of changes necessary to ensure quality. A first step
      toward developing informed radiation dose reduction goals is to become familiar
      with the radiation dose values and radiation-associated health risks reported in
      the literature. Next, to determine the baseline dose values for a CT study at a
      particular institution, dose data can be collected from the CT scanners,
      interpreted, tabulated, and graphed. CT protocols can be modified to reduce
      overall effective dose by using techniques such as automated exposure control and
      iterative reconstruction, as well as by decreasing the number of scanning phases,
      increasing the section thickness, and adjusting the peak voltage (kVp setting),
      tube current-time product (milliampere-seconds), and pitch. Last, PDSA (plan, do,
      study, act) cycles can be established to detect and minimize negative effects of
      dose reduction methods on image quality.

PMID- 21969663
TI  - Hepatocellular carcinoma lesion characterization: single-institution clinical
      performance review of multiphase gadolinium-enhanced MR imaging--comparison to
      prior same-center results after MR systems improvements.
AB  - PURPOSE: To measure diagnostic performance in the detection of hepatocellular
      carcinoma (HCC) by using the most recent technology and multiphase gadolinium
      enhanced magnetic resonance (MR) imaging and to compare with earlier results at
      the same institution. MATERIALS AND METHODS: This retrospective study was
      institutional review board approved and HIPAA compliant. Informed consent was
      obtained. Between January 2008 and April 2010, 101 patients underwent liver
      transplantation and pretransplantation abdominal MR imaging within 90 days.
      Prospective image interpretations from the clinical record were reviewed for
      documentation of HCC, including size, number, and location. Liver explant
      histologic examination provided the reference standard for lesion analysis and
      was performed in axial gross slices in conjunction with the MR imaging report for
      direct comparison. Tumors were categorized according to size (>= 2 cm or <2 cm),
      and MR imaging detection sensitivity, specificity, predictive values, and
      accuracy were calculated according to category. The Fisher exact test was used to
      compare results from this study against prior reported results. RESULTS: Thirty
      five (34.7%) of 101 patients had HCC at explant analysis. Patient-based analysis
      of all lesions showed a sensitivity and specificity of 97.1% (34 of 35) and 100%
      (66 of 66), respectively. For lesions 2 cm or larger, MR imaging had a
      sensitivity and specificity of 100% (23 of 23) and 100% (78 of 78), respectively.
      For lesions smaller than 2 cm, MR imaging had a sensitivity and specificity of
      82.6% (19 of 23) and 100% (78 of 78), respectively. Lesion-based sensitivity for
      all tumors was 91.4% (53 of 58) in the current study, compared with 77.8% in 2007
      (P = .07). For lesions smaller than 2 cm, the sensitivity was 87.5% (28 of 32) in
      the current study, compared with 55.6% previously (P = .02). CONCLUSION: MR
      imaging remains a highly accurate diagnostic method for the preoperative
      evaluation of HCC, and detection of small (<2 cm) tumors has been significantly
      improved compared with that of earlier studies.

PMID- 21969664
TI  - Peripheral arterial occlusive disease: diagnostic performance and effect on
      therapeutic management of 64-section CT angiography.
AB  - PURPOSE: To evaluate the diagnostic performance and effect on therapeutic
      management of 64-section computed tomographic (CT) angiography in the assessment
      of steno-occlusive disease in patients with peripheral arterial disease (PAD),
      with conventional digital subtraction angiography (DSA) as the reference
      standard. MATERIALS AND METHODS: The study protocol was approved by the
      institutional review board, and written informed consent was obtained from all
      patients. A total of 212 patients with symptomatic PAD underwent CT angiography
      and subsequent DSA. For stenosis analysis (>= 70% stenosis), the arterial bed was
      divided into 35 segments and evaluated by three readers. Interobserver agreement
      was determined with generalized kappa statistics. Accuracy, sensitivity,
      specificity, positive predictive value (PPV), negative predictive value (NPV),
      positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were
      calculated. In addition, according to the TransAtlantic Inter-Society Consensus
      (TASC) Document on Management of Peripheral Arterial Disease guidelines,
      treatment recommendations based on CT angiographic and DSA findings were
      compared. McNemar test was used to prove significant differences between CT
      angiographic and DSA findings. RESULTS: A total of 7420 arterial segments were
      evaluated, with excellent agreement between readers (kappa >= 0.928). On a
      segmental basis, both sensitivity and specificity for stenosis of 70% or more
      were at least 96% (3072 of 3113 segments and 4141 of 4279 segments,
      respectively), with an accuracy of 98% (7213 of 7392 segments), a PPV of 96%
      (3072 of 3187 segments), an NPV of 99% (3141 of 3187 segments), a PLR of 36.7,
      and an NLR of 0.013. There was no significant difference between CT angiographic
      and DSA findings (P = .62-.87). In accordance with TASC II guidelines, 49
      patients were referred for conservative treatment, 87 underwent endovascular
      procedures, 38 underwent surgery, and 17 received hybrid treatment. Therapy
      recommendations based on CT angiographic findings alone were identical to those
      based on DSA findings in all but one patient. CONCLUSION: The diagnostic
      performance of 64-section CT angiography is excellent in patients with clinical
      symptoms of PAD. The results can be used to effectively guide therapeutic
      decision making in these patients.

PMID- 21969665
TI  - CT angiographic measurement of vascular blood flow velocity by using projection
      data.
AB  - PURPOSE: To determine whether flow velocity can be measured by using projection
      data from computed tomographic (CT) scans obtained during contrast material
      injection in a phantom model. MATERIALS AND METHODS: The authors constructed a
      12.7-mm-diameter single-channel flow phantom with constant water flow velocity
      settings of 25.3, 43.9, and 70.5 cm/sec. For each flow velocity, serial axial
      scans were obtained with 16-section multidetector CT while a 10-mL bolus of
      contrast material was injected upstream of the imaging plane. For each bolus
      injection, the CT projection data from the scan with the sharpest increase in
      magnitude of detected contrast material was used for flow velocity measurements.
      Flow velocity was calculated as the ratio of distance between CT detector rows
      and the corresponding time lag in the contrast enhancement curves and was
      correlated with the reference velocities. Five separate contrast material
      injections and CT measurements were made for each flow velocity setting. RESULTS:
      The correlation coefficient between the CT measurements of flow velocity and the
      reference measurements was 0.98 (P < .05). The mean CT measurements of flow
      velocity were 34.2, 53.9, and 80.8 cm/sec for slow, moderate, and fast velocity
      settings, respectively, overestimating the corresponding actual flow velocities
      by 26%, 18%, and 13% and showing precision values (coefficients of variation) of
      5.2%, 3.7%, and 6.6%. CONCLUSION: Flow velocity can be measured from row-to-row
      multidetector CT projectional data obtained during a single gantry revolution as
      a bolus of contrast material flows through a vascular phantom. With further
      development, this novel technique could potentially provide physiologic
      information to complement the anatomic CT angiographic findings of vascular
      disease.

PMID- 21969666
TI  - Image quality and radiation exposure using different low-dose scan protocols in
      dual-source CT coronary angiography: randomized study.
AB  - PURPOSE: To compare image quality, radiation dose, and their relationship with
      heart rate of computed tomographic (CT) coronary angiographic scan protocols by
      using a 128-section dual-source CT scanner. MATERIALS AND METHODS: Institutional
      review board approved the study; all patients gave informed consent. Two hundred
      seventy-two patients (175 men, 97 women; mean ages, 58 and 59 years,
      respectively) referred for CT coronary angiography were categorized according to
      heart rate: less than 65 beats per minute (group A) and 65 beats per minute or
      greater (group B). Patients were randomized to undergo prospective high-pitch
      spiral scanning and narrow-window prospective sequential scanning in group A (n =
      160) or wide-window prospective sequential scanning and retrospective spiral
      scanning in group B (n = 112). Image quality was graded (1 = nondiagnostic; 2 =
      artifacts present, diagnostic; 3 = no artifacts) and compared (Mann-Whitney and
      Student t tests). RESULTS: In group A, mean image quality grade was significantly
      lower with high-pitch spiral versus sequential scanning (2.67 +/- 0.38 [standard
      deviation] vs 2.86 +/- 0.21; P < .001). In a subpopulation (heart rate, <55 beats
      per minute), mean image quality grade was similar (2.81 +/- 0.30 vs 2.94 +/-
      0.08; P = .35). In group B, image quality grade was comparable between sequential
      and retrospective spiral scanning (2.81 +/- 0.28 vs 2.80 +/- 0.38; P = .54). Mean
      estimated radiation dose was significantly lower (high-pitch spiral vs sequential
      scanning) in group A (for 100 kV, 0.81 mSv +/- 0.30 vs 2.74 mSv +/- 1.14 [P <
      .001]; for 120 kV, 1.65 mSv +/- 0.69 vs 4.21 mSv +/- 1.20 [P < .001]) and in
      group B (sequential vs retrospective spiral scanning) (for 100 kV, 4.07 mSv +/-
      1.07 vs 5.54 mSv +/- 1.76 [P = .02]; for 120 kV, 7.50 mSv +/- 1.79 vs 9.83 mSv +/
      3.49 [P = .1]). CONCLUSION: A high-pitch spiral CT coronary angiographic
      protocol should be applied in patients with regular and low (<55 beats per
      minute) heart rates; a sequential protocol is preferred in all others.

PMID- 21969667
TI  - Gliomas: Histogram analysis of apparent diffusion coefficient maps with standard-
      or high-b-value diffusion-weighted MR imaging--correlation with tumor grade.
AB  - PURPOSE: To explore the role of histogram analysis of apparent diffusion
      coefficient (ADC) maps based on entire tumor volume data in determining glioma
      grade and to evaluate the diagnostic performance of ADC maps at standard (1000
      sec/mm(2)) and high (3000 sec/mm(2)) b values. MATERIALS AND METHODS: This
      retrospective study was approved by the institutional review board, and informed
      consent was waived. Twenty-seven patients with astrocytic tumors underwent
      diffusion-weighted magnetic resonance imaging with b values of 1000 and 3000
      sec/mm(2), and the corresponding ADC maps were calculated (ADC(1000) and
      ADC(3000), respectively). Regions of interest containing the lesion were drawn on
      every section of the ADC map containing the tumor and were summated to derive
      volume-based data of the entire tumor. Histogram parameters were correlated with
      tumor grade by using repeated measurements analysis of variance, the Tukey-Kramer
      test for post hoc comparisons, and an unpaired Student t test. Receiver operating
      characteristic (ROC) curves were constructed to determine the optimum threshold
      for each histogram parameter, and sensitivity and specificity were assessed.
      RESULTS: Minimum ADC(1000) and ADC(3000) both decreased with increasing tumor
      grade. The 50th and 75th percentiles of cumulative ADC(1000) histograms showed
      significant differences between grades (P = .015 and .001, respectively), while
      the fifth and 75th percentiles of cumulative ADC(3000) histograms showed such
      differences (P = .015 and .014, respectively). Minimum ADC and the fifth
      percentile for both ADC(1000) (P < .001 and P = .024, respectively) and ADC(3000)
      (P < .001 and P = .001, respectively) proved to be significant histogram
      parameters for differentiating high- from low-grade gliomas. The diagnostic value
      of the parameters derived from ADC(1000) and ADC(3000) were compared, and a
      significant difference (0.202, P = .014) was found between the areas under the
      ROC curve of the fifth percentiles for ADC(1000) and ADC(3000). CONCLUSION:
      Histogram analysis of ADC maps based on entire tumor volume can be a useful tool
      for grading gliomas. The fifth percentile of the cumulative ADC histogram
      obtained at a high b value was the most promising parameter for differentiating
      high- from low-grade gliomas.

PMID- 21969668
TI  - Long biceps tendon: normal position, shape, and orientation in its groove in
      neutral position and external and internal rotation.
AB  - PURPOSE: To characterize the position, shape, and orientation of the long biceps
      tendon (LBT) on transverse magnetic resonance (MR) images acquired in neutral
      position and in maximal external and internal rotation of the shoulder in
      asymptomatic volunteers. MATERIALS AND METHODS: Informed consent was obtained
      from all volunteers for this institutional review board-approved study. Fifty
      three asymptomatic volunteers (mean age, 33 years; age range, 21-58 years) were
      included. The position of the LBT with respect to the bicipital groove was
      measured by two musculoskeletal radiologists on three levels along the bicipital
      groove on axial MR images in neutral position and in external and internal
      rotation of the shoulder. The shape of the LBT was classified as round, oval,
      flat, or comma shaped, and the orientation of the LBT was measured. RESULTS: The
      position of the LBT changed significantly at the entrance into the bicipital
      groove in the mediolateral and anteroposterior directions (P < .01). The changes
      of LBT position in external rotation and internal rotation compared with the
      neutral position were markedly small (< 1.5 mm). Medial eccentricity of the LBT
      was greatest in the neutral shoulder position at all measurement levels.
      Differences in LBT shape and orientation were found between the neutral position
      and external or internal rotation and between the three measurement levels.
      CONCLUSION: The position of the LBT is only slightly dependent on shoulder
      rotation. LBT eccentricity is maximal in the neutral position. Rotational
      misplacement during image acquisition does not increase LBT eccentricity.

PMID- 21969669
TI  - Towards the virtual physiological human: mathematical and computational case
      studies.

PMID- 21969670
TI  - A tentative taxonomy for predictive models in relation to their falsifiability.
AB  - The growing importance of predictive models in biomedical research raises some
      concerns on the correct methodological approach to the falsification of such
      models, as they are developed in interdisciplinary research contexts between
      physics, biology and medicine. In each of these research sectors, there are
      established methods to develop cause-effect explanations for observed phenomena,
      which can be used to predict: epidemiological models, biochemical models,
      biophysical models, Bayesian models, neural networks, etc. Each research sector
      has accepted processes to verify how correct these models are (falsification).
      But interdisciplinary research imposes a broader perspective, which encompasses
      all possible models in a general methodological framework of falsification. The
      present paper proposes a general definition of 'scientific model' that makes it
      possible to categorize predictive models into broad categories. For each of these
      categories, generic falsification strategies are proposed, except for the so
      called 'abductive' models. For this category, which includes artificial neural
      networks, Bayesian models and integrative models, the definition of a generic
      falsification strategy requires further investigation by researchers and
      philosophers of science.

PMID- 21969671
TI  - Transport in the placenta: homogenizing haemodynamics in a disordered medium.
AB  - The placenta is an essential component of the life-support system for the
      developing foetus, enabling nutrients and waste to be exchanged between the
      foetal and maternal circulations. Maternal blood flows between the densely packed
      branches of villous trees, within which are foetal vessels. Here, we explore some
      of the challenges in modelling maternal haemodynamic transport using
      homogenization approaches. We first show how two measures can be used to estimate
      the minimum distance over which the distribution of villous branches appears
      statistically homogeneous. We then analyse a simplified model problem (solute
      transport by a unidirectional flow past a distribution of point sinks) to assess
      the accuracy of homogenization approximations as a function of governing
      parameters (Peclet and Damkohler numbers) and the statistical properties of the
      sink distribution. The difference between the leading-order homogenization
      approximation and the exact solute distribution is characterized by large spatial
      gradients at the scale of individual villi and substantial fluctuations that can
      be correlated over lengthscales comparable to the whole domain. This study
      highlights the importance of quantifying errors owing to spatial disorder in
      multi-scale approximations of physiological systems.

PMID- 21969672
TI  - Nonlinear models of development, amplification and compression in the mammalian
      cochlea.
AB  - This paper reviews current understanding and presents new results on some of the
      nonlinear processes that underlie the function of the mammalian cochlea. These
      processes occur within mechano-sensory hair cells that form part of the organ of
      Corti. After a general overview of cochlear physiology, mathematical modelling
      results are presented in three parts. First, the dynamic interplay between ion
      channels within the sensory inner hair cells is used to explain some new
      electrophysiological recordings from early development. Next, the state of the
      art is reviewed in modelling the electro-motility present within the outer hair
      cells (OHCs), including the current debate concerning the role of cell body
      motility versus active hair bundle dynamics. A simplified model is introduced
      that combines both effects in order to explain observed amplification and
      compression in experiments. Finally, new modelling evidence is presented that
      structural longitudinal coupling between OHCs may be necessary in order to
      capture all features of the observed mechanical responses.

PMID- 21969673
TI  - A human ventricular cell model for investigation of cardiac arrhythmias under
      hyperkalaemic conditions.
AB  - In this study, several modifications were introduced to a recently proposed human
      ventricular action potential (AP) model so as to render it suitable for the study
      of ventricular arrhythmias. These modifications were driven by new sets of
      experimental data available from the literature and the analysis of several well
      established cellular arrhythmic risk biomarkers, namely AP duration at 90 per
      cent repolarization (APD(90)), AP triangulation, calcium dynamics, restitution
      properties, APD(90) adaptation to abrupt heart rate changes, and rate dependence
      of intracellular sodium and calcium concentrations. The proposed methodology
      represents a novel framework for the development of cardiac cell models. Five
      stimulation protocols were applied to the original model and the ventricular AP
      model developed here to compute the described arrhythmic risk biomarkers. In
      addition, those models were tested in a one-dimensional fibre in which
      hyperkalaemia was simulated by increasing the extracellular potassium
      concentration, [K(+)](o). The effective refractory period (ERP), conduction
      velocity (CV) and the occurrence of APD alternans were investigated. Results show
      that modifications improved model behaviour as verified by: (i) AP triangulation
      well within experimental limits (the difference between APD at 50 and 90 per cent
      repolarization being 78.1 ms); (ii) APD(90) rate adaptation dynamics
      characterized by fast and slow time constants within physiological ranges (10.1
      and 105.9 s); and (iii) maximum S1S2 restitution slope in accordance with
      experimental data (S(S1S2)=1.0). In simulated tissues under hyperkalaemic
      conditions, APD(90) progressively shortened with the degree of hyperkalaemia,
      whereas ERP increased once a threshold in [K(+)](o) was reached ([K(+)](o)~6 mM).
      CV decreased with [K(+)](o), and conduction was blocked for [K(+)](o)>10.4 mM.
      APD(90) alternans were observed for [K(+)](o)>9.8 mM. Those results adequately
      reproduce experimental observations. This study demonstrated the value of basing
      the development of AP models on the computation of arrhythmic risk biomarkers, as
      opposed to joining together independently derived ion channel descriptions to
      produce a whole-cell AP model, with the new framework providing a better picture
      of the model performance under a variety of stimulation conditions. On top of
      replicating experimental data at single-cell level, the model developed here was
      able to predict the occurrence of APD(90) alternans and areas of conduction block
      associated with high [K(+)](o) in tissue, which is of relevance for the
      investigation of the arrhythmogenic substrate in ischaemic hearts.

PMID- 21969674
TI  - Image-based multi-scale modelling and validation of radio-frequency ablation in
      liver tumours.
AB  - The treatment of cancerous tumours in the liver remains clinically challenging,
      despite the wide range of treatment possibilities, including radio-frequency
      ablation (RFA), high-intensity focused ultrasound and resection, which are
      currently available. Each has its own advantages and disadvantages. For non- or
      minimally invasive modalities, such as RFA, considered here, it is difficult to
      monitor the treatment in vivo. This is particularly problematic in the liver,
      where large blood vessels act as heat sinks, dissipating delivered heat and
      shrinking the size of the lesion (the volume damaged by the heat treatment)
      locally; considerable experience is needed on the part of the clinician to
      optimize the heat treatment to prevent recurrence. In this paper, we outline our
      work towards developing a simulation tool kit that could be used both to optimize
      treatment protocols in advance and to train the less-experienced clinicians for
      RFA treatment of liver tumours. This tool is based on a comprehensive
      mathematical model of bio-heat transfer and cell death. We show how simulations
      of ablations in two pigs, based on individualized imaging data, compare directly
      with experimentally measured lesion sizes and discuss the likely sources of error
      and routes towards clinical implementation. This is the first time that such a
      'loop' of mathematical modelling and experimental validation in vivo has been
      performed in this context, and such validation enables us to make quantitative
      estimates of error.

PMID- 21969675
TI  - Pulmonary embolism: predicting disease severity.
AB  - Pulmonary embolism (PE) is the most common cause of acute pulmonary hypertension,
      yet it is commonly undiagnosed, with risk of death if not recognized promptly and
      managed accordingly. Patients typically present with hypoxemia and hypomania,
      although the presentation varies greatly, being confounded by co-morbidities such
      as pre-existing cardio-respiratory disease. Previous studies have demonstrated
      variable patient outcomes in spite of similar extent and distribution of
      pulmonary vascular occlusion, but the path physiological determinants of outcome
      remain unclear. Computational models enable exact control over many of the
      compounding factors leading to functional outcomes and therefore provide a useful
      tool to understand and assess these mechanisms. We review the current state of
      pulmonary blood flow models. We present a pilot study within 10 patients
      presenting with acute PE, where patient-derived vascular occlusions are imposed
      onto an existing model of the pulmonary circulation enabling predictions of
      resultant haemodynamic after embolus occlusion. Results show that mechanical
      obstruction alone is not sufficient to cause pulmonary arterial hypertension,
      even when up to 65 per cent of lung tissue is occluded. Blood flow is found to
      preferentially redistribute to the gravitationally non-dependent regions. The
      presence of an additional downstream occlusion is found to significantly increase
      pressures.

PMID- 21969676
TI  - Influence of high-frequency cyclical stimulation on the bone fracture-healing
      process: mathematical and experimental models.
AB  - Mechanical stimulation affects the evolution of healthy and fractured bone.
      However, the effect of applying cyclical mechanical stimuli on bone healing has
      not yet been fully clarified. The aim of the present study was to determine the
      influence of a high-frequency and low-magnitude cyclical displacement of the
      fractured fragments on the bone-healing process. This subject is studied
      experimentally and computationally for a sheep long bone. On the one hand, the
      mathematical computational study indicates that mechanical stimulation at high
      frequencies can stimulate and accelerate the process of chondrogenesis and
      endochondral ossification and consequently the bony union of the fracture. This
      is probably achieved by the interstitial fluid flow, which can move nutrients and
      waste from one place to another in the callus. This movement of fluid modifies
      the mechanical stimulus on the cells attached to the extracellular matrix. On the
      other hand, the experimental study was carried out using two sheep groups. In the
      first group, static fixators were implanted, while, in the second one, identical
      devices were used, but with an additional vibrator. This vibrator allowed a
      cyclic displacement with low magnitude and high frequency (LMHF) to be applied to
      the fractured zone every day; the frequency of stimulation was chosen from
      mechano-biological model predictions. Analysing the results obtained for the
      control and stimulated groups, we observed improvements in the bone-healing
      process in the stimulated group. Therefore, in this study, we show the potential
      of computer mechano-biological models to guide and define better mechanical
      conditions for experiments in order to improve bone fracture healing. In fact,
      both experimental and computational studies indicated improvements in the healing
      process in the LMHF mechanically stimulated fractures. In both studies, these
      improvements could be associated with the promotion of endochondral ossification
      and an increase in the rate of cell proliferation and tissue synthesis.

PMID- 21969677
TI  - Simulating the physiology of athletes during endurance sports events: modelling
      human energy conversion and metabolism.
AB  - The human physiological system is stressed to its limits during endurance sports
      competition events. We describe a whole body computational model for energy
      conversion during bicycle racing. About 23 per cent of the metabolic energy is
      used for muscle work, the rest is converted to heat. We calculated heat transfer
      by conduction and blood flow inside the body, and heat transfer from the skin by
      radiation, convection and sweat evaporation, resulting in temperature changes in
      25 body compartments. We simulated a mountain time trial to Alpe d'Huez during
      the Tour de France. To approach the time realized by Lance Armstrong in 2004,
      very high oxygen uptake must be sustained by the simulated cyclist. Temperature
      was predicted to reach 39 degrees C in the brain, and 39.7 degrees C in leg
      muscle. In addition to the macroscopic simulation, we analysed the buffering of
      bursts of high adenosine triphosphate hydrolysis by creatine kinase during
      cyclical muscle activity at the biochemical pathway level. To investigate the low
      oxygen to carbohydrate ratio for the brain, which takes up lactate during
      exercise, we calculated the flux distribution in cerebral energy metabolism.
      Computational modelling of the human body, describing heat exchange and energy
      metabolism, makes simulation of endurance sports events feasible.

PMID- 21969678
TI  - Virtual surgeries in patients with congenital heart disease: a multi-scale
      modelling test case.
AB  - The objective of this work is to perform a virtual planning of surgical repairs
      in patients with congenital heart diseases--to test the predictive capability of
      a closed-loop multi-scale model. As a first step, we reproduced the pre-operative
      state of a specific patient with a univentricular circulation and a bidirectional
      cavopulmonary anastomosis (BCPA), starting from the patient's clinical data.
      Namely, by adopting a closed-loop multi-scale approach, the boundary conditions
      at the inlet and outlet sections of the three-dimensional model were
      automatically calculated by a lumped parameter network. Successively, we
      simulated three alternative surgical designs of the total cavopulmonary
      connection (TCPC). In particular, a T-junction of the venae cavae to the
      pulmonary arteries (T-TCPC), a design with an offset between the venae cavae (O
      TCPC) and a Y-graft design (Y-TCPC) were compared. A multi-scale closed-loop
      model consisting of a lumped parameter network representing the whole circulation
      and a patient-specific three-dimensional finite volume model of the BCPA with
      detailed pulmonary anatomy was built. The three TCPC alternatives were
      investigated in terms of energetics and haemodynamics. Effects of exercise were
      also investigated. Results showed that the pre-operative caval flows should not
      be used as boundary conditions in post-operative simulations owing to changes in
      the flow waveforms post-operatively. The multi-scale approach is a possible
      solution to overcome this incongruence. Power losses of the Y-TCPC were lower
      than all other TCPC models both at rest and under exercise conditions and it
      distributed the inferior vena cava flow evenly to both lungs. Further work is
      needed to correlate results from these simulations with clinical outcomes.

PMID- 21969679
TI  - Verification of cardiac tissue electrophysiology simulators using an N-version
      benchmark.
AB  - Ongoing developments in cardiac modelling have resulted, in particular, in the
      development of advanced and increasingly complex computational frameworks for
      simulating cardiac tissue electrophysiology. The goal of these simulations is
      often to represent the detailed physiology and pathologies of the heart using
      codes that exploit the computational potential of high-performance computing
      architectures. These developments have rapidly progressed the simulation capacity
      of cardiac virtual physiological human style models; however, they have also made
      it increasingly challenging to verify that a given code provides a faithful
      representation of the purported governing equations and corresponding solution
      techniques. This study provides the first cardiac tissue electrophysiology
      simulation benchmark to allow these codes to be verified. The benchmark was
      successfully evaluated on 11 simulation platforms to generate a consensus gold
      standard converged solution. The benchmark definition in combination with the
      gold-standard solution can now be used to verify new simulation codes and
      numerical methods in the future.

PMID- 21969680
TI  - Active touch sensing.
AB  - Active sensing systems are purposive and information-seeking sensory systems.
      Active sensing usually entails sensor movement, but more fundamentally, it
      involves control of the sensor apparatus, in whatever manner best suits the task,
      so as to maximize information gain. In animals, active sensing is perhaps most
      evident in the modality of touch. In this theme issue, we look at active touch
      across a broad range of species from insects, terrestrial and marine mammals,
      through to humans. In addition to analysing natural touch, we also consider how
      engineering is beginning to exploit physical analogues of these biological
      systems so as to endow robots with rich tactile sensing capabilities. The
      different contributions show not only the varieties of active touch--antennae,
      whiskers and fingertips--but also their commonalities. They explore how active
      touch sensing has evolved in different animal lineages, how it serves to provide
      rapid and reliable cues for controlling ongoing behaviour, and even how it can
      disintegrate when our brains begin to fail. They demonstrate that research on
      active touch offers a means both to understand this essential and primary sensory
      modality, and to investigate how animals, including man, combine movement with
      sensing so as to make sense of, and act effectively in, the world.

PMID- 21969681
TI  - Active tactile exploration for adaptive locomotion in the stick insect.
AB  - Insects carry a pair of actively movable feelers that supply the animal with a
      range of multimodal information. The antennae of the stick insect Carausius
      morosus are straight and of nearly the same length as the legs, making them ideal
      probes for near-range exploration. Indeed, stick insects, like many other
      insects, use antennal contact information for the adaptive control of locomotion,
      for example, in climbing. Moreover, the active exploratory movement pattern of
      the antennae is context-dependent. The first objective of the present study is to
      reveal the significance of antennal contact information for the efficient
      initiation of climbing. This is done by means of kinematic analysis of freely
      walking animals as they undergo a tactually elicited transition from walking to
      climbing. The main findings are that fast, tactually elicited re-targeting
      movements may occur during an ongoing swing movement, and that the height of the
      last antennal contact prior to leg contact largely predicts the height of the
      first leg contact. The second objective is to understand the context-dependent
      adaptation of the antennal movement pattern in response to tactile contact. We
      show that the cycle frequency of both antennal joints increases after obstacle
      contact. Furthermore, inter-joint coupling switches distinctly upon tactile
      contact, revealing a simple mechanism for context-dependent adaptation.

PMID- 21969682
TI  - Active touch in orthopteroid insects: behaviours, multisensory substrates and
      evolution.
AB  - Orthopteroid insects (cockroaches, crickets, locusts and related species) allow
      examination of active sensory processing in a comparative framework. Some
      orthopteroids possess long, mobile antennae endowed with many chemo- and
      mechanoreceptors. When the antennae are touched, an animal's response depends
      upon the identity of the stimulus. For example, contact with a predator may lead
      to escape, but contact with a conspecific may usually not. Active touch of an
      approaching object influences the likelihood that a discrimination of identity
      will be made. Using cockroaches, we have identified specific descending
      mechanosensory interneurons that trigger antennal-mediated escape. Crucial
      sensory input to these cells comes from chordotonal organs within the antennal
      base. However, information from other receptors on the base or the long antennal
      flagellum allows active touch to modulate escape probability based on stimulus
      identity. This is conveyed, at least to some extent, by textural information.
      Guidance of the antennae in active exploration depends on visual information.
      Some of the visual interneurons and the motor neurons necessary for visuomotor
      control have been identified. Comparisons across Orthoptera suggest an
      evolutionary model where subtle changes in the architecture of interneurons, and
      of sensorimotor control loops, may explain differing levels of vision-touch
      interaction in the active guidance of behaviour.

PMID- 21969683
TI  - The sense of touch in the star-nosed mole: from mechanoreceptors to the brain.
AB  - Star-nosed moles are somatosensory specialists that explore their environment
      with 22 appendages that ring their nostrils. The appendages are covered with
      sensory domes called Eimer's organs. Each organ is associated with a Merkel cell
      neurite complex, a lamellated corpuscle, and a series of 5-10 free nerve endings
      that form a circle of terminal swellings. Anatomy and electrophysiological
      recordings suggest that Eimer's organs detect small shapes and textures. There
      are parallels between the organization of the mole's somatosensory system and
      visual systems of other mammals. The centre of the star is a tactile fovea used
      for detailed exploration of objects and prey items. The tactile fovea is over
      represented in the neocortex, and this is evident in the modular, anatomically
      visible representation of the star. Multiple maps of the star are visible in
      flattened cortical preparations processed for cytochrome oxidase or NADPH
      diaphorase. Star-nosed moles are the fastest known foragers among mammals, able
      to identify and consume a small prey item in 120 ms. Together these behavioural
      and nervous system specializations have made star-nosed moles an intriguing model
      system for examining general and specialized aspects of mammalian touch.

PMID- 21969684
TI  - The neurobiology of Etruscan shrew active touch.
AB  - The Etruscan shrew, Suncus etruscus, is not only the smallest terrestrial mammal,
      but also one of the fastest and most tactile hunters described to date. The
      shrew's skeletal muscle consists entirely of fast-twitch types and lacks slow
      fibres. Etruscan shrews detect, overwhelm, and kill insect prey in large numbers
      in darkness. The cricket prey is exquisitely mechanosensitive and fast-moving,
      and is as big as the shrew itself. Experiments with prey replica show that shape
      cues are both necessary and sufficient for evoking attacks. Shrew attacks are
      whisker guided by motion- and size-invariant Gestalt-like prey representations.
      Shrews often attack their prey prior to any signs of evasive manoeuvres. Shrews
      whisk at frequencies of approximately 14 Hz and can react with latencies as short
      as 25-30 ms to prey movement. The speed of attacks suggests that shrews identify
      and classify prey with a single touch. Large parts of the shrew's brain respond
      to vibrissal touch, which is represented in at least four cortical areas
      comprising collectively about a third of the cortical volume. Etruscan shrews can
      enter a torpid state and reduce their body temperature; we observed that cortical
      response latencies become two to three times longer when body temperature drops
      from 36 degrees C to 24 degrees C, suggesting that endothermy contributes to the
      animal's high-speed sensorimotor performance. We argue that small size, high
      speed behaviour and extreme dependence on touch are not coincidental, but reflect
      an evolutionary strategy, in which the metabolic costs of small body size are
      outweighed by the advantages of being a short-range high-speed touch and kill
      predator.

PMID- 21969685
TI  - Active vibrissal sensing in rodents and marsupials.
AB  - In rats, the long facial whiskers (mystacial macrovibrissae) are repetitively and
      rapidly swept back and forth during exploration in a behaviour known as
      'whisking'. In this paper, we summarize previous evidence from rats, and present
      new data for rat, mouse and the marsupial grey short-tailed opossum (Monodelphis
      domestica) showing that whisking in all three species is actively controlled both
      with respect to movement of the animal's body and relative to environmental
      structure. Using automatic whisker tracking, and Fourier analysis, we first show
      that the whisking motion of the mystacial vibrissae, in the horizontal plane, can
      be approximated as a blend of two sinusoids at the fundamental frequency (mean
      8.5, 11.3 and 7.3 Hz in rat, mouse and opossum, respectively) and its second
      harmonic. The oscillation at the second harmonic is particularly strong in mouse
      (around 22 Hz) consistent with previous reports of fast whisking in that species.
      In all three species, we found evidence of asymmetric whisking during head
      turning and following unilateral object contacts consistent with active control
      of whisker movement. We propose that the presence of active vibrissal touch in
      both rodents and marsupials suggests that this behavioural capacity emerged at an
      early stage in the evolution of therian mammals.

PMID- 21969686
TI  - Radial distance determination in the rat vibrissal system and the effects of
      Weber's law.
AB  - Rats rhythmically tap and brush their vibrissae (whiskers) against objects to
      tactually explore the environment. To extract a complex feature such as the
      contour of an object, the rat must at least implicitly estimate radial object
      distance, that is, the distance from the base of the vibrissa to the point of
      object contact. Radial object distance cannot be directly measured, however,
      because there are no mechanoreceptors along the vibrissa. Instead, the mechanical
      signals generated by the vibrissa's interaction with the environment must be
      transmitted to mechanoreceptors near the vibrissa base. The first part of this
      paper surveys the different mechanical methods by which the rat could determine
      radial object distance. Two novel methods are highlighted: one based on
      measurement of bending moment and axial force at the vibrissa base, and a second
      based on measurement of how far the vibrissa rotates beyond initial contact. The
      second part of the paper discusses the application of Weber's law to two methods
      for radial distance determination. In both cases, Weber's law predicts that the
      rat will have greatest sensing resolution close to the vibrissa tip. These
      predictions could be tested with behavioural experiments that measure the
      perceptual acuity of the rat.

PMID- 21969687
TI  - Whisking and whisker kinematics during a texture classification task.
AB  - Rats explore objects by rhythmically whisking with their vibrissae. The goal of
      the present study is to learn more about the motor output used by rats to acquire
      texture information as well as the whisker motion evoked by texture contact. We
      trained four rats to discriminate between different grooved textures and used
      high-speed video to characterize whisker motion during the task. The variance in
      whisking parameters among subjects was notable. After whisker trimming, the
      animals changed their behaviour in ways that appear consistent with an
      optimization of whisker movement to compensate for lost information. These
      results lead to the intriguing notion that the rats use an information-seeking
      'cognitive' motor strategy, instead of a rigid motor programme. Distinct
      stick/slip events occurred during texture palpation and their frequency increased
      in relation to the spatial frequency of the grooves. The results allow a
      preliminary assessment of three candidate texture-coding mechanisms-the number of
      grooves encountered during each touch, the temporal difference between groove
      contacts and the spatial pattern of groove contacts across the whiskers.

PMID- 21969688
TI  - Motor-sensory convergence in object localization: a comparative study in rats and
      humans.
AB  - In order to identify basic aspects in the process of tactile perception, we
      trained rats and humans in similar object localization tasks and compared the
      strategies used by the two species. We found that rats integrated temporally
      related sensory inputs ('temporal inputs') from early whisk cycles with spatially
      related inputs ('spatial inputs') to align their whiskers with the objects; their
      perceptual reports appeared to be based primarily on this spatial alignment. In a
      similar manner, human subjects also integrated temporal and spatial inputs, but
      relied mainly on temporal inputs for object localization. These results suggest
      that during tactile object localization, an iterative motor-sensory process
      gradually converges on a stable percept of object location in both species.

PMID- 21969689
TI  - Flow sensing by pinniped whiskers.
AB  - Beside their haptic function, vibrissae of harbour seals (Phocidae) and
      California sea lions (Otariidae) both represent highly sensitive hydrodynamic
      receptor systems, although their vibrissal hair shafts differ considerably in
      structure. To quantify the sensory performance of both hair types, isolated
      single whiskers were used to measure vortex shedding frequencies produced in the
      wake of a cylinder immersed in a rotational flow tank. These measurements
      revealed that both whisker types were able to detect the vortex shedding
      frequency but differed considerably with respect to the signal-to-noise ratio
      (SNR). While the signal detected by sea lion whiskers was substantially corrupted
      by noise, harbour seal whiskers showed a higher SNR with largely reduced noise.
      However, further analysis revealed that in sea lion whiskers, each noise signal
      contained a dominant frequency suggested to function as a characteristic carrier
      signal. While in harbour seal whiskers the unique surface structure explains its
      high sensitivity, this more or less steady fundamental frequency might represent
      the mechanism underlying hydrodynamic reception in the fast swimming sea lion by
      being modulated in response to hydrodynamic stimuli impinging on the hair.

PMID- 21969690
TI  - Biomimetic vibrissal sensing for robots.
AB  - Active vibrissal touch can be used to replace or to supplement sensory systems
      such as computer vision and, therefore, improve the sensory capacity of mobile
      robots. This paper describes how arrays of whisker-like touch sensors have been
      incorporated onto mobile robot platforms taking inspiration from biology for
      their morphology and control. There were two motivations for this work: first, to
      build a physical platform on which to model, and therefore test, recent
      neuroethological hypotheses about vibrissal touch; second, to exploit the control
      strategies and morphology observed in the biological analogue to maximize the
      quality and quantity of tactile sensory information derived from the artificial
      whisker array. We describe the design of a new whiskered robot, Shrewbot, endowed
      with a biomimetic array of individually controlled whiskers and a
      neuroethologically inspired whisking pattern generation mechanism. We then
      present results showing how the morphology of the whisker array shapes the
      sensory surface surrounding the robot's head, and demonstrate the impact of
      active touch control on the sensory information that can be acquired by the
      robot. We show that adopting bio-inspired, low latency motor control of the
      rhythmic motion of the whiskers in response to contact-induced stimuli usefully
      constrains the sensory range, while also maximizing the number of whisker
      contacts. The robot experiments also demonstrate that the sensory consequences of
      active touch control can be usefully investigated in biomimetic robots.

PMID- 21969691
TI  - Haptic object perception: spatial dimensionality and relation to vision.
AB  - Enabled by the remarkable dexterity of the human hand, specialized haptic
      exploration is a hallmark of object perception by touch. Haptic exploration
      normally takes place in a spatial world that is three-dimensional; nevertheless,
      stimuli of reduced spatial dimensionality are also used to display spatial
      information. This paper examines the consequences of full (three-dimensional)
      versus reduced (two-dimensional) spatial dimensionality for object processing by
      touch, particularly in comparison with vision. We begin with perceptual
      recognition of common human-made artefacts, then extend our discussion of spatial
      dimensionality in touch and vision to include faces, drawing from research on
      haptic recognition of facial identity and emotional expressions. Faces have often
      been characterized as constituting a specialized input for human perception. We
      find that contrary to vision, haptic processing of common objects is impaired by
      reduced spatial dimensionality, whereas haptic face processing is not. We
      interpret these results in terms of fundamental differences in object perception
      across the modalities, particularly the special role of manual exploration in
      extracting a three-dimensional structure.

PMID- 21969692
TI  - Human perception of shape from touch.
AB  - In this paper, I focus on the role of active touch in three aspects of shape
      perception and discrimination studies. First an overview is given of curvature
      discrimination experiments. The most prominent result is that first-order
      stimulus information (that is, the difference in attitude or slope over the
      stimulus) is the dominant factor determining the curvature threshold. Secondly, I
      compare touch under bimanual and two-finger performance with unimanual and one
      finger performance. Consistently, bimanual or two-finger performance turned out
      to be worse. The most likely explanation for the former finding is that a loss of
      accuracy during intermanual comparisons is owing to interhemispheric relay.
      Thirdly, I address the presence of strong after-effects after just briefly
      touching a shape. These after-effects have been measured and studied in various
      conditions (such as, static, dynamic, transfer to other hand or finger).
      Combination of the results of these studies leads to the insight that there are
      possibly different classes of after-effect: a strong after-effect, caused by
      immediate contact with the stimulus, that does only partially transfer to the
      other hand, and one much less strong after-effect, caused by moving over the
      stimulus for a certain period, which shows a full transfer to other fingers.

PMID- 21969693
TI  - Is there a 'plenhaptic' function?
AB  - One approach to gauge the complexity of the computational problem underlying
      haptic perception is to determine the number of dimensions needed to describe it.
      In vision, the number of dimensions can be estimated to be seven. This
      observation raises the question of what is the number of dimensions needed to
      describe touch. Only with certain simplified representations of mechanical
      interactions can this number be estimated, because it is in general infinite.
      Organisms must be sensitive to considerably reduced subsets of all possible
      measurements. These reductions are discussed by considering the sensing
      apparatuses of some animals and the underlying mechanisms of two haptic
      illusions.

PMID- 21969694
TI  - Obtaining information by dynamic (effortful) touching.
AB  - Dynamic touching is effortful touching. It entails deformation of muscles and
      fascia and activation of the embedded mechanoreceptors, as when an object is
      supported and moved by the body. It is realized as exploratory activities that
      can vary widely in spatial and temporal extents (a momentary heft, an extended
      walk). Research has revealed the potential of dynamic touching for obtaining non
      visual information about the body (e.g. limb orientation), attachments to the
      body (e.g. an object's height and width) and the relation of the body both to
      attachments (e.g. hand's location on a grasped object) and surrounding surfaces
      (e.g. places and their distances). Invariants over the exploratory activity (e.g.
      moments of a wielded object's mass distribution) seem to ground this 'information
      about'. The conception of a haptic medium as a nested tensegrity structure has
      been proposed to express the obtained information realized by myofascia
      deformation, by its invariants and transformations. The tensegrity proposal
      rationalizes the relative indifference of dynamic touch to the site of mechanical
      contact (hand, foot, torso or probe) and the overtness of exploratory activity.
      It also provides a framework for dynamic touching's fractal nature, and the
      finding that its degree of fractality may matter to its accomplishments.

PMID- 21969695
TI  - Light touch for balance: influence of a time-varying external driving signal.
AB  - Sensory information about body sway is used to drive corrective muscle action to
      keep the body's centre of mass located over the base of support provided by the
      feet. Loss of vision, by closing the eyes, usually results in increased sway as
      indexed by fluctuations (i.e. standard deviation, s.d.) in the velocity of a
      marker at C7 on the neck, s.d. dC7. Variability in the rate of change of centre
      of pressure (s.d. dCoP), which indexes corrective muscle action, also increases
      during upright standing with eyes closed. Light touch contact by the tip of one
      finger with an environmental surface can reduce s.d. dC7 and s.d. dCoP as
      effectively as opening the eyes. We review studies of light touch and balance and
      then describe a novel paradigm for studying the nature of somatosensory
      information contributing to effects of light touch balance. We show that 'light
      tight touch' contact by the index finger held in the thimble of a haptic device
      results in increased anteroposterior (AP) sway with entraining by either simple
      or complex AP sinusoidal oscillations of the haptic device. Moreover, sway is
      also increased when the haptic device plays back the pre-recorded AP sway path of
      another person. Cross-correlations between hand and C7 motion reveal a 176 ms
      lead for the hand and we conclude that light tight touch affords an efficient
      route for somatosensory feedback support for balance. Furthermore, we suggest
      that the paradigm has potential to contribute to the understanding of
      interpersonal postural coordination with light touch in future research.

PMID- 21969696
TI  - The role of self-touch in somatosensory and body representation disorders after
      stroke.
AB  - Somatosensory impairments occur in about half of the cases of stroke. These
      impairments range from primary deficits in tactile detection and the perception
      of features, to higher order impairments in haptic object recognition and bodily
      experience. In this paper, we review the influence of active- and self-touch on
      somatosensory impairments after stroke. Studies have shown that self-touch
      improves tactile detection in patients with primary tactile deficits. A small
      number of studies concerned with the effect of self-touch on bodily experience in
      healthy individuals have demonstrated that self-touch influences the structural
      representation of one's own body. In order to better understand the effect of
      self-touch on body representations, we present an informal study of a stroke
      patient with somatoparaphrenia and misoplegia. The role of self-touch on body
      ownership was investigated by asking the patient to stroke the impaired left hand
      and foreign hands. The patient reported ownership and a change in affect over all
      presented hands through self-touch. The time it took to accomplish ownership
      varied, based on the resemblance of the foreign hand to the patient's own hand.
      Our findings suggest that self-touch can modulate impairments in body ownership
      and affect, perhaps by helping to reinstate the representation of the body.

PMID- 21969697
TI  - Modelling natural and artificial hands with synergies.
AB  - We report on recent work in modelling the process of grasping and active touch by
      natural and artificial hands. Starting from observations made in human hands
      about the correlation of degrees of freedom in patterns of more frequent use
      (postural synergies), we consider the implications of a geometrical model
      accounting for such data, which is applicable to the pre-grasping phase occurring
      when shaping the hand before actual contact with the grasped object. To extend
      applicability of the synergy model to study force distribution in the actual
      grasp, we introduce a modified model including the mechanical compliance of the
      hand's musculotendinous system. Numerical results obtained by this model indicate
      that the same principal synergies observed from pre-grasp postural data are also
      fundamental in achieving proper grasp force distribution. To illustrate the
      concept of synergies in the dual domain of haptic sensing, we provide a review of
      models of how the complexity and heterogeneity of sensory information from touch
      can be harnessed in simplified, tractable abstractions. These abstractions are
      amenable to fast processing to enable quick reflexes as well as elaboration of
      high-level percepts. Applications of the synergy model to the design and control
      of artificial hands and tactile sensors are illustrated.

PMID- 21969698
TI  - Diagnosis of lymph node metastasis in uterine cervical cancer: usefulness of
      computer-aided diagnosis with comprehensive evaluation of MR images and clinical
      findings.
AB  - BACKGROUND: Lymph node (LN) status is an important parameter for determining the
      treatment strategy and for predicting the prognosis for patients with uterine
      cervical cancer. Computer-aided diagnosis (CAD) can be feasible for
      differentiating metastatic from non-metastatic lymph nodes in patients with
      uterine cervical cancer. PURPOSE: To determine the usefulness of CAD that
      comprehensively evaluates MR images and clinical findings for detecting LN
      metastasis in uterine cervical cancer. MATERIAL AND METHODS: In 680 LNs from 143
      patients who underwent radical hysterectomy for uterine cervical cancer, the CAD
      system using the Bayesian classifier estimated the probability of metastasis
      based on MR findings and clinical findings. We compared the diagnostic accuracy
      for detecting metastatic LNs in the CAD and MR findings. RESULTS: Metastasis was
      diagnosed in 70 (12%) LNs from 34 (24%) patients. The area under ROC curves of
      CAD (0.924) was greater than those of the mean ADC (0.854), minimum ADC (0.849),
      maximum ADC (0.827), short-axis diameter (0.856) and long-axis diameter (0.753)
      (P < 0.05). The specificity and accuracy of the CAD (86%, 86%) were greater than
      those of the mean ADC (77%, 77%), maximum ADC (77%, 77%), minimum ADC (68%, 70%),
      and short-axis diameter (65%, 67%) (P < 0.05). CONCLUSION: CAD system can improve
      the diagnostic performance of MR for detecting metastatic LNs in uterine cervical
      cancer.

PMID- 21969699
TI  - Classification of persistent primitive trigeminal artery (PPTA): a
      reconsideration based on MRA.
AB  - BACKGROUND: Persistent primitive trigeminal artery (PPTA) is the most common
      permanent carotid-basilar anastomosis. Magnetic resonance angiography (MRA) has
      become the primary non-invasive imaging technique for evaluation of cerebral
      vascular anatomy and can provide detailed 3D imaging of intracranial vessels.
      PURPOSE: To evaluate the usefulness of MRA for the detection of PPTA and to re
      classify its variations based on the embryologic types of PcomA and its
      relationship with the basilar artery and its branches. MATERIAL AND METHODS: Of
      the total 7329 patients who underwent MRA at our institution from March 2008
      through November 2010, we retrospectively analyzed the MRAs of 24 patients with a
      PPTA. Special attention was given to defining the relationship of the PPTA and
      the basilar artery with PcomA and to determine the site of origin, size, and
      course of the PPTA. The PPTA classification included five types based on their
      anatomic relationship to the neighboring arteries. Clinical features and
      associated vascular anomalies are also described. RESULTS: Twenty-four (17 women
      and seven men, 34 ~ 81 years of age, mean age 59.67 years) of the 7329 patients
      had a PPTA (0.33 %). Eleven cases (45.8%) were classified as type 1, three
      (12.5%) as type 2, five (20.8%) as type 3, one (4.2%) as type 4, and four (16.7%)
      as type 5b. Fifteen PPTAs (62.5%) were located on the left side and nine were
      located (37.5%) on the right side. The basilar artery proximal to the insertion
      of the PPTA showed severe to moderate hypoplasia in 13 cases (54%). Nine
      intracranial artery aneurysms were detected in seven (29%) of the 24 study
      patients. CONCLUSION: This study revealed five types of PPTA and necessitates an
      adjustment of the previous classification of PPTA on the basis of our MRA
      examinations. A PPTA should be considered by both the clinician and the
      radiologist who interpret MR angiography.

PMID- 21969700
TI  - Initially non-diagnostic ultrasound-guided fine needle aspiration cytology of
      thyroid nodules: value and management.
AB  - BACKGROUND: Ultrasound (US)-guided fine needle aspiration cytology (FNAC) is an
      accurate, reliable, and simple method to identify a thyroid nodule as benign or
      malignant. However, non-diagnostic cytology results for thyroid nodules are a
      major limitation of US-guided FNAC. PURPOSE: To investigate the incidence of
      thyroid cancer among cases with non-diagnostic results on FNAC and to provide
      suggestions for the management of thyroid nodules that are initially non
      diagnostic by FNAC according to ultrasonographic findings. MATERIAL AND METHODS:
      From July 2006 to December 2009, 10,317 thyroid nodules in 6684 consecutive
      patients underwent US-guided FNAC at our institute. Among these, 871 thyroid
      nodules (8.4%) were diagnosed as non-diagnostic on initial cytologic evaluation
      and 196 underwent a second or third FNAC. Twenty-seven thyroid nodules (18.9%)
      underwent surgery, while 116 thyroid nodules were cytologically confirmed as
      benign with no remarkable change on follow-up US were included. We
      retrospectively reviewed the US findings for a total of 143 thyroid nodules (123
      benign nodules and 20 malignant nodules). The US features that we compared
      included composition, echogenicity, margin, calcifications, shape, and underlying
      echogenicity. RESULTS: In total, thyroid cancer was diagnosed in 20 nodules
      (14.0%). The size of the nodule was significantly associated with malignancy (P <
      0.05). Most of the sonographically probable benign nodules were found to be
      benign (97.6%). Suspicious nodules on US were thyroid cancer in 43.2% of cases.
      Marked hypoechogenicity, microlobulated or irregular margin, microcalcifications,
      and taller-than-wide shape were significant US findings that correlated with
      malignancy (P < 0.05). The diagnostic performance of ultrasound for initially non
      diagnostic thyroid nodules was as follows: sensitivity of 90.0%, specificity of
      65.0%, positive predictive value of 29.5%, and negative predictive value of
      97.6%. CONCLUSION: In terms of management of thyroid nodules with non-diagnostic
      FNAC cytology, US evaluation is a feasible and useful method for predicting
      malignancy.

PMID- 21969701
TI  - Accuracy of CT-guided biopsies in 158 patients with thoracic spinal lesions.
AB  - BACKGROUND: Inconsistent accuracies of CT-guided thoracic spinal biopsies have
      been reported in previous studies. PURPOSE: To determine the accuracy of CT
      guided thoracic spinal biopsy, to compare the results with those previously
      reported, and to determine if there are any factors that influence the accuracy
      of CT-guided thoracic spinal biopsy. MATERIAL AND METHODS: In total, 158
      consecutive CT-guided percutaneous thoracic spine procedures (performed at the
      Department of Spinal Surgery, Xi'an Red Cross Hospital between April 2000 and
      July 2010) were reviewed. The 158 lesions were categorized by location and
      radiographic features. Pathological and clinical follow-up were used to determine
      accuracy. RESULTS: The diagnostic accuracy of CT-guided thoracic spinal biopsy
      was 90.5% overall. Biopsy of metastatic bone disease (98.2%) was significantly
      more accurate than biopsies of primary tumors (80.9%) and of hematological
      malignancies (47.0%) (P < 0.05 and P < 0.005, respectively). The diagnostic
      accuracy of CT-guided thoracic spinal biopsy was significantly higher for the
      lower thoracic spine (97.6%) than for the middle (90.0%) or upper thoracic spine
      (80.4%) (P < 0.05 and P < 0.025, respectively). The diagnostic accuracy was
      significantly higher for lytic lesions (96.4%) than for sclerotic lesions (81.3%)
      (P < 0.010). The accuracy of biopsies performed using the transpedicular approach
      (91.0%) was not significantly different from that of biopsies performed using
      posterolateral approaches (91.5%) (0.25 < P < 0.5). CONCLUSION: Percutaneous CT
      guided thoracic spinal biopsy is a viable alternative to open surgical biopsy.
      The diagnostic accuracy was not affected by any of the variables except for
      lesion level, histology, and radiographic features.

PMID- 21969702
TI  - Multiparametric analysis of magnetic resonance images for glioma grading and
      patient survival time prediction.
AB  - BACKGROUND: A systematic comparison of magnetic resonance imaging (MRI) options
      for glioma diagnosis is lacking. PURPOSE: To investigate multiple MR-derived
      image features with respect to diagnostic accuracy in tumor grading and survival
      prediction in glioma patients. MATERIAL AND METHODS: T1 pre- and post-contrast,
      T2 and dynamic susceptibility contrast scans of 74 glioma patients with
      histologically confirmed grade were acquired. For each patient, a set of
      statistical features was obtained from the parametric maps derived from the
      original images, in a region-of-interest encompassing the tumor volume. A forward
      stepwise selection procedure was used to find the best combinations of features
      for grade prediction with a cross-validated logistic model and survival time
      prediction with a cox proportional-hazards regression. RESULTS: Presence/absence
      of enhancement paired with kurtosis of the FM (first moment of the first-pass
      curve) was the feature combination that best predicted tumor grade (grade II vs.
      grade III-IV; median AUC = 0.96), with the main contribution being due to the
      first of the features. A lower predictive value (median AUC = 0.82) was obtained
      when grade IV tumors were excluded. Presence/absence of enhancement alone was the
      best predictor for survival time, and the regression was significant (P <
      0.0001). CONCLUSION: Presence/absence of enhancement, reflecting transendothelial
      leakage, was the feature with highest predictive value for grade and survival
      time in glioma patients.

PMID- 21969703
TI  - In-vivo near-infrared optical imaging of growing osteosarcoma cell lesions
      xenografted in mice: dual-channel quantitative evaluation of volume and
      mineralization.
AB  - BACKGROUND: In a previous study using a rodent osteosarcoma-grafted rat model, in
      which cell-dependent mineralization was previously demonstrated to proportionally
      increase with growth, we performed a quantitative analysis of mineral deposit
      formation using (99m)Tc-HMDP and found some weaknesses, such as longer
      acquisition time and narrower dynamic ranges (i.e. images easily saturated). The
      recently developed near-infrared (NIR) optical imaging technique is expected to
      non-invasively evaluate changes in living small animals in a quantitative manner.
      PURPOSE: To test the feasibility of NIR imaging with a dual-channel system as a
      better alternative for bone scintigraphy by quantitatively evaluating
      mineralization along with the growth of osteosarcoma lesions in a mouse-xenograft
      model. MATERIAL AND METHODS: The gross volume and mineralization of osteosarcoma
      lesions were evaluated in living mice simultaneously with dual-channels by NIR
      dye-labeled probes, 2-deoxyglucose (DG) and pamidronate (OS), respectively. To
      verify these quantitative data, retrieved osteosarcoma lesions were then
      subjected to ex-vivo imaging, weighing under wet conditions, microfocus-computed
      tomography (MUCT) analysis, and histopathological examination. RESULTS: Because
      of less scattering and no anatomical overlapping, as generally shown, specific
      fluorescence signals targeted to the osteosarcoma lesions could be determined
      clearly by ex-vivo imaging. These data were well positively correlated with the
      in-vivo imaging data (r > 0.8, P < 0.02). Other good to excellent correlations (r
      > 0.8, P < 0.02) were observed between DG accumulation and tumor gross volume and
      between OS accumulation and mineralization volume. CONCLUSION: This in-vivo NIR
      imaging technique using DG and OS is sensitive to the level to simultaneously
      detect and quantitatively evaluate the growth and mineralization occuring in this
      type of osteosarcoma lesions of living mice without either invasion or sacrifice.
      By possible mutual complementation, this dual imaging system might be useful for
      accurate diagnosis even in the presence of overlapping tissues.

PMID- 21969704
TI  - Calcium scoring in unenhanced and enhanced CT data of the aorta-iliacal arteries:
      impact of image acquisition, reconstruction, and analysis parameter settings.
AB  - BACKGROUND: Several studies have been published on the matter of abdominal aortic
      and iliac calcifications and the association to clinical entities such as
      diabetes mellitus and renal failure. However, comparing of these studies is
      questionable since quantification methods for atherosclerosis differ. PURPOSE: To
      evaluate the effect of image acquisition settings, reconstruction parameters, and
      analysis methods on calcium quantification in the abdominal aorta. MATERIAL AND
      METHODS: Calcium scores were retrospectively determined on standardized abdominal
      CT scans of 15 patients. Two researchers obtained calcium scores with 10
      different lower thresholds (LT) (130, 145, 160, 175, 200, 300, 400, 500, 600,
      1000) in CT scans with and without contrast enhancement, with slice thicknesses
      (ST) varying between 2.0-5.0 mm for the non-contrast-enhanced series and between
      1.0-5.0 mm for the contrast-enhanced series. In addition calcium scores obtained
      with two convolution kernels (B10f, B20f) were compared. Inter-observer
      variability was calculated. RESULTS: Calcium scoring at higher STs is
      overestimated compared to smaller STs and this effect was more pronounced with
      increasing calcium loads. Concerning the convolution kernel, scores obtained with
      kernel B10f were overestimated compared to kernel B20f. Increase of LT resulted
      in a decrease of the calcium score and scoring in contrast-enhanced series
      resulted in higher scores compared to non-contrast-enhanced series. These effects
      are more apparent in patients with higher calcium loads. Calcium scoring
      reproducibility with the reference standard is limited for the aorta-iliac
      trajectory, whereas scoring with the remaining settings is reproducible.
      CONCLUSION: Scores obtained with different settings cannot be compared. The inter
      observer reproducibility was limited using the reference standard and practical
      difficulties were substantial. Scoring with higher LT, ST, and contrast
      enhancement is faster and has less practical difficulties.

PMID- 21969705
TI  - Visual and quantitative assessment of lateral lumbar spinal canal stenosis with
      magnetic resonance imaging.
AB  - BACKGROUND: Lateral lumbar spinal canal stenosis is a common etiology of lumbar
      radicular symptoms. Quantitative measurements have commonly demonstrated better
      repeatability than visual assessments. We are not aware of any studies examining
      the repeatability of quantitative assessment of the lateral canal. PURPOSE: To
      evaluate the repeatability of visual assessments and newly developed quantitative
      measurements of lateral lumbar spinal canal stenosis using magnetic resonance
      imaging (MRI). MATERIAL AND METHODS: Twenty-eight patients with lateral lumbar
      spinal canal stenosis or prior spinal surgery with recurrent symptoms were imaged
      with MRI. A radiologist, a neurosurgeon and a spine research trainee graded
      visually and quantitatively subarticular (n = 188) and foraminal zones (n = 260)
      of the lateral spinal canal. Quantitative measurements included the minimal
      subarticular width and the cross-sectional area of the foramen. RESULTS: The
      repeatability of visual assessment at the subarticular zone and foraminal zones
      between raters varied from 0.45-0.59 and 0.42-0.53, respectively. Similarly, the
      intraclass correlation coefficients for the quantitative measurements varied from
      0.67-0.71 and 0.66-0.76, respectively. The intra-rater repeatability for the
      visual assessments of the subarticular and foraminal zones was 0.70 and 0.62,
      respectively, while the corresponding intraclass correlation coefficients for
      quantitative measurements were 0.83 and 0.81, respectively. CONCLUSION: Inter
      rater repeatability of visual assessments of lateral stenosis is moderate,
      whereas quantitative measurements of both subarticular width and the cross
      sectional area of the foramen have substantial reproducibility and may be
      particularly useful for longitudinal studies and research purposes. The clinical
      value of these parameters requires further study.

PMID- 21969706
TI  - Detection of pulmonary nodules by C-arm CT using a phantom lung: comparison with
      CT.
AB  - BACKGROUND: Evaluation of detection of lung nodules by C-arm CT (CACT) is
      important before this procedure can be used to guide percutaneous lung
      interventions. PURPOSE: To compare the efficacy of CACT with CT in the detection
      of pulmonary nodules using a phantom lung. MATERIAL AND METHODS: A phantom lung
      containing 12 phantom nodules in four sizes (5 mm/8 mm/10 mm/12 mm) and three CT
      values (one solid nodule, +100 HU; two ground glass nodules, -630 and -800 HU)
      was used. Six sessions of CACT (slice thickness 4.5 mm) and CT (slice thickness 5
      mm) were performed. In each session, the locations of nodules were arbitrarily
      changed in the phantom. Three radiologists assessed the detection of a total of
      72 nodules. Statistical analysis was performed for the sensitivity and positive
      predictive value of lung nodules between CACT and CT by the McNemar test and
      paired t-test (P < 0.05). RESULTS: Sensitivity did not differ between CACT and
      CT, respectively (reader 1, 82% vs. 88%, P = 0.22; reader 2, 82% vs. 78%, P =
      0.37; reader 3, 79% vs. 83%, P = 0.48). For nodules of 8 mm or larger, the
      sensitivity increased for each reader and showed no significant difference
      between CACT vs. CT. The positive predictive value did not differ between CACT
      and CT. CONCLUSION: In this phantom study, CT and CACT show similar sensitivity
      for the detection of pulmonary nodules. CACT could be used in percutaneous
      interventional procedures in the lungs.

PMID- 21969707
TI  - Evaluation of apparent diffusion coefficient mappings in amnestic mild cognitive
      impairment using an image analysis software brain search.
AB  - BACKGROUND: The apparent diffusion coefficient (ADC) from diffusion-weighted
      imaging (DWI) can quantify alterations in water diffusivity resulting from
      microscopic structural changes from amnestic mild cognitive impairment (aMCI) and
      Alzheimer's disease (AD). PURPOSE: To investigate the ADC value for aMCI and AD
      using Brain Search (BS) software based on anatomical volumes of interest (AVOI).
      MATERIAL AND METHODS: In total, 174 aged people were screened, and 25 patients
      with AD, 26 patients with aMCI, and 18 normal controls (NCs) were recruited. DWI
      was performed at 1.5 T with a fluid-attenuated inversion recovery (FLAIR), and
      the independent ADC mapping was generated after imaging acquisition. Ninety
      regional parcellations were adopted in a Brain Search (BS) based on the automated
      anatomic labeling atlas. The gray scale intensities (water diffusivity) from the
      collected ADC mappings were analyzed with BS. The mean value of each anatomical
      brain region was compared among aMCI, AD, and NC. The statistically significant
      (P < 0.05) group differences are displayed in color. RESULTS: During the
      pathological process of AD, the changes of water diffusivity appeared first in
      the left hippocampus, then gradually progressed to the bilateral sides and
      eventually displayed right lateralization. The ADC values from aMCI were
      obviously elevated compared to the values from the NC group in the left limbic
      cortex. Between the AD and NC groups, the significantly different brain areas
      included the bilateral hippocampus, the Cingulum_Mid, the ParaHippocampal_R, and
      the Temporal and Frontal lobes. There was a negative correlation between the ADC
      values and the scores from MMSE, MoCA, the Digit test, Raven's IQ, and WAIS IQ.
      Additionally, the ADC values were positively correlated with the scores from CDR,
      ADL, and ADAS-Cog. CONCLUSION: The water diffusivity for aMCI and AD displays
      asymmetric anatomical lateralization. The water diffusivity alterations can be
      analyzed and visualized with our newly designed analytic imaging software, BS,
      which can be used as a good reference for examining and diagnosing aMCI and AD
      patients.

PMID- 21969708
TI  - MRI findings of cancers preoperatively diagnosed as pure DCIS at core needle
      biopsy.
AB  - BACKGROUND: Under-estimation of invasion components occur occasionally at core
      needle diagnosed ductal carcinoma in situ (DCIS) that may change the prognosis or
      treatment planning. PURPOSE: To determine whether enhanced magnetic resonance
      imaging (MRI) features of biopsy-proven ductal cancers in situ help predict the
      under-estimation of invasive breast cancers. MATERIAL AND METHODS: After a
      retrospective review of the enhanced MRI features on preoperative proven breast
      ductal cancers in situ by biopsy, tumor morphology (mass and non-mass), enhancing
      curve patterns, and non-mass enhanced appearances were compared between pure
      ductal cancers in situ and invasive ductal cancers (IDCs) after surgery. A
      statistical analysis was performed, and P values <0.05 were deemed significant.
      RESULTS: Twenty-five breast cancers from 24 women were analyzed. Eleven DCIS
      remained as DCISs, and 14 were upgraded to IDC after surgery. Eight of 14 IDCs
      (57%) and one of 11 DCISs (9%) presented as mass lesions; otherwise six (43%)
      IDCs and 10 (91%) DCISs were non-mass lesions (P = 0.013). Among the non-mass
      cancers, six of 10 DCISs (60%) were focally enhanced and six of 6 IDCs (100%)
      were segmentally enhanced. The overall cancer sizes measured on enhanced MRI were
      moderately correlated with histopathology, with a Spearman's rank correlation
      coefficient of 0.656 (P = 0.001). The mean diameter of the IDCs was larger than
      that of the pure DCISs on enhanced MRI (2.69 +/- 1.42 cm for IDC and 1.62 +/-
      1.03 cm for DCIS; P = 0.048). The cut-off size was optimally selected at 1.95 cm
      with a 64% sensitivity and a 77% specificity, using a receiver-operating
      characteristic curve. The enhancement curves, with washout or persistent rising,
      were statistically insignificant (P = 0.085 and 0.93, respectively). CONCLUSION:
      Enhanced MRI provided informative morphology and size features that might help to
      predict the underestimation of invasiveness in preoperative biopsy-proven DCIS.

PMID- 21969709
TI  - Comparison of FDG-PET/CT and bone scintigraphy for detection of bone metastases
      in breast cancer.
AB  - BACKGROUND: Bone scintigraphy is the standard procedure for the detection of bone
      metastases in breast cancer patients. FDG-PET/CT has been reported to be a
      sensitive tool for tumor staging in different malignant diseases. However, its
      accuracy for the detection of bone metastases has not been compared to bone
      scintigraphy. PURPOSE: To compare whole-body FDG-PET/CT and bone scintigraphy for
      the detection of bone metastases on a lesion basis in breast cancer patients.
      MATERIAL AND METHODS: Twenty-nine consecutive women (mean age 58 years, range 35
      78 years) with histologically proven breast cancer were assessed with bone
      scintigraphy and whole-body FDG-PET/CT. Twenty-one patients (72%) were suffering
      from primary breast cancer and eight patients (28%) were in aftercare with a
      history of advanced breast cancer. Both imaging procedures were assessed for bone
      metastases by a radiologist and a nuclear medicine physician. Concordant readings
      between bone scintigraphy and FDG-PET/CT were taken as true. Discordant readings
      were verified with additional MRI imaging in all patients and follow-up studies
      in most patients. RESULTS: A total of 132 lesions were detected on bone
      scintigraphy, FDG-PET/CT or both. According to the reference standard, 70/132
      lesions (53%) were bone metastases, 59/132 lesions (45%) were benign, and three
      lesions (2%) remained unclear. The sensitivity of bone scintigraphy was 76%
      (53/70) compared to 96% (67/70) for FDG-PET/CT. The specificity of bone
      scintigraphy and FDG-PET/CT was 95% (56/59) and 92% (54/59), respectively.
      According to the reference standard bone metastases were present in eight out of
      the 29 patients (28%), whereas 20 patients (69%) were free of bone metastases.
      One (3%) patient had inconclusive readings on both modalities as well as on MRI
      and follow-up studies. Bone scintigraphy and FDG-PET/CT correctly identified
      seven out of eight patients with bone metastases and 20 out of 20 patients free
      of metastases. CONCLUSION: On a lesion-basis whole-body FDG-PET/CT is more
      sensitive and equally specific for the detection of bone metastases compared with
      bone scintigraphy.

PMID- 21969710
TI  - MDCT angiography with 3D image reconstructions in the evaluation of failing
      arteriovenous fistulas and grafts in hemodialysis patients.
AB  - BACKGROUND: Arteriovenous fistulas and grafts are the methods of choice for
      vascular access in renal failure patients in need of hemodialysis. Their major
      complication, however, is stenosis, which might lead to thrombosis. PURPOSE: To
      demonstrate the usefulness of 16-MDCTA with 3D image reconstructions, in long
      term hemodialysis patients with dysfunctional arteriovenous fistulas and grafts
      (AVF and AVG). MATERIAL AND METHODS: During a 17-month period, 31 patients with
      dysfunctional AVF and AVG (24 AVF and seven AVG) were examined with MDCTA with 3D
      image postprocessing. Parameters such as comprehension of the anatomy, quality of
      contrast enhancement, and pathological vascular changes were measured. DSA was
      then performed in 24 patients. RESULTS: MDCTA illustrated the anatomy of the
      AVF/AVG and the entire vascular tree to the heart, in a detailed and
      comprehensive manner in 93.5% of the evaluated segments, and depicted pathology
      of AVF/AVG or pathology of the associated vasculature. MDCTA demonstrated a total
      of 38 significant stenoses in 25 patients. DSA verified 37 stenoses in 24
      patients and demonstrated two additional stenoses. MDCTA had thus a sensitivity
      of 95%. All 24 patients were treated with percutaneous transluminal angioplasty
      (PTA) with good technical results. CONCLUSION: MDCTA with 3D reconstructions of
      dysfunctioning AVFs and AVGs in hemodialysis patients is an accurate and reliable
      diagnostic method helping customize future intervention.

PMID- 21969711
TI  - Melittin attenuates liver injury in thioacetamide-treated mice through modulating
      inflammation and fibrogenesis.
AB  - Liver fibrosis represents a process of healing and scarring in response to
      chronic liver injury. Following injury, an acute inflammation response takes
      place resulting in moderate cell necrosis and extracellular matrix damage.
      Melittin, the major bioactive component in the venom of honey bee Apis mellifera,
      is a 26-residue amphipathic peptide with well-known cytolytic, antimicrobial and
      proinflammatory properties. However, the molecular mechanisms responsible for the
      anti-inflammatory activity of melittin have not been elucidated in liver
      fibrosis. We investigated whether melittin ameliorates liver inflammation and
      fibrosis in thioacetamide (TAA)-induced liver fibrosis. Two groups of mice were
      treated with TAA (200 mg/L, in drinking water), one of the groups of mice was co
      treated with melittin (0.1 mg/kg) for 12 weeks while the other was not. Hepatic
      stellate cells (HSCs) were cultured with tumor necrosis factor alpha in the
      absence or presence of melittin. Melittin suppresses the expression of
      proinflammatory cytokines through the nuclear factor (NF)-kappaB signaling
      pathway. Moreover, melittin reduces the activity of HSCs in vitro, and decreases
      the expression of fibrotic gene responses in TAA-induced liver fibrosis. Taken
      together, melittin prevents TAA-induced liver fibrosis by inhibiting liver
      inflammation and fibrosis, the mechanism of which is the interruption of the NF
      kappaB signaling pathway. These results suggest that melittin could be an
      effective agent for preventing liver fibrosis.

PMID- 21969713
TI  - Impending federal budget cuts and dramatic impacts upon pharmacy and pharmacy
      education.

PMID- 21969712
TI  - Maternal hepatic growth response to pregnancy in the mouse.
AB  - Pregnancy is characterized by physiological adjustments in the maternal
      compartment. In this investigation, the influence of pregnancy on maternal liver
      was examined in CD-1 mice. Dramatic changes were observed in the size of the
      maternal liver during pregnancy. Livers doubled in weight from the non-pregnant
      state to day 18 of pregnancy. The pregnancy-induced hepatomegaly was a
      physiological event of liver growth confirmed by DNA content increase and
      detection of hepatocyte hyperplasia and hypertrophy. Growth of the liver was
      initiated following implantation and peaked at parturition. The expression and/or
      activities of key genes known to regulate liver regeneration, a phenomenon of
      liver growth compensatory to liver mass loss, were investigated. The results
      showed that pregnancy-dependent liver growth was associated with interleukin (IL)
      6, tumor necrosis factor alpha, c-Jun and IL-1beta, but independent of hepatocyte
      growth factor, fibroblast growth factor 1, tumor necrosis factor receptor 1,
      constitutive androstane receptor and pregnane X receptor. Furthermore, maternal
      liver growth was associated with the activation of hepatic signal transducer and
      activator of transcription 3, beta-catenin and epidermal growth factor receptor,
      but pregnancy did not activate hepatic c-Met. The findings suggest that the
      molecular mechanisms regulating pregnancy-induced liver growth and injury-induced
      liver regeneration exhibit overlapping features but are not identical. In
      summary, the liver of the mouse adapts to the demands of pregnancy via a dramatic
      growth response driven by hepatocyte proliferation and size increase.

PMID- 21969714
TI  - Protect our house.

PMID- 21969715
TI  - Use of adjunct faculty members in classroom teaching in departments of pharmacy
      practice.
AB  - OBJECTIVE: To determine trends among departments of pharmacy practice regarding
      use of adjunct faculty members for classroom-based teaching and to assess
      departmental support provided to these faculty members. METHODS: Chairs of
      pharmacy practice departments in US colleges and school of pharmacy were
      contacted by e-mail and asked to complete an 11-item electronic survey
      instrument. RESULTS: Chair respondents reported an average of 5.7 adjunct faculty
      members hired to teach required courses and 1.8 adjunct faculty members hired to
      teach elective courses. Compensation averaged $108 per lecture hour and $1,257
      per 1-credit-hour course. Twenty-five percent of the respondents expected to hire
      more adjunct faculty members to teach required courses in the upcoming year due
      to curricular changes, faculty hiring freezes, and the shortage of full-time
      faculty members. Only 7% of respondents reported that they provided a teaching
      mentor and 14% offered no support to their adjunct faculty members. CONCLUSIONS:
      Departments of pharmacy practice commonly use adjunct faculty members to teach
      required and elective courses. Given the pharmacy faculty shortage, this trend is
      expected to increase and may be an area for future faculty development.

PMID- 21969716
TI  - Peer- and self-grading compared to faculty grading.
AB  - OBJECTIVES: To determine the reliability and value of peer- and self -reported
      evaluations in the grading of pharmacy students. METHODS: Mean student peer- and
      self- reported grades were compared to faculty grades in the advanced pharmacy
      practice experience (APPE) and seminar presentation courses. Responses from
      pharmacy school alumni regarding curricular peer- and self-reported evaluations
      were solicited using an online survey tool. RESULTS: Self-reported student grades
      were lower than the faculty-reported grade overall and for the formal
      presentation component of the APPE course grading rubric. Self-reported grades
      were no different than faculty-reported grades for the seminar course. Students
      graded their peers higher than did faculty members for both the seminar and APPE
      courses on all components of the grading rubric. The majority of pharmacy alumni
      conducted peer- and self-evaluations (64% and 85%, respectively) at least
      annually and considered peer- and self-evaluations useful in assessing students'
      work in group projects, oral presentations, and professional skills. CONCLUSION:
      The combination of self-, peer-, and faculty-assessments using a detailed grading
      rubric offers an opportunity to meet accreditation standards and better prepare
      pharmacy students for their professional careers.

PMID- 21969717
TI  - Pharmacy student perceptions of adverse event reporting.
AB  - OBJECTIVE: To assess US pharmacy students' knowledge and perceptions of adverse
      event reporting. METHODS: To gauge pharmacy students' impressions of adverse
      event reporting, a 10-question survey instrument was administered that addressed
      student perceptions of the reporting procedures of the Food and Drug
      Administration (FDA) and pharmaceutical manufacturers, as well as student
      understanding of the Health Insurance Portability and Accountability Act (HIPAA)
      and its relationship to adverse event reporting. RESULTS: Two hundred twenty
      eight pharmacy students responded to the survey. The majority of respondents
      believed that the FDA is more likely than a pharmaceutical company to take action
      regarding an adverse event. There were misconceptions relating to the way adverse
      event reports are handled and the influence of HIPAA regulations on reporting.
      CONCLUSIONS: Communication between the FDA and pharmaceutical manufacturers
      regarding adverse event reports is not well understood by pharmacy students.
      Education about adverse event reporting should evolve so that by the time
      pharmacy students become practitioners, they are well acquainted with the
      relevance and importance of adverse event reporting.

PMID- 21969718
TI  - Student evaluations of the portfolio process.
AB  - OBJECTIVE: To evaluate pharmacy students' perceived benefits of the portfolio
      process and to gather suggestions for improving the process. METHODS: A
      questionnaire was designed and administered to 250 first-, second-, and third
      year pharmacy students at the University of Arizona College of Pharmacy. RESULTS:
      Although the objectives of the portfolio process were for students to understand
      the expected outcomes, understand the impact of extracurricular activities on
      attaining competencies, identify what should be learned, identify their strengths
      and weaknesses, and modify their approach to learning, overall students perceived
      the portfolio process as having less than moderate benefit. First-year students
      wanted more examples of portfolios while second- and third-year students
      suggested that more time with their advisor would be beneficial. CONCLUSIONS: The
      portfolio process will continue to be refined and efforts made to improve
      students' perceptions of the process as it is intended to develop the self
      assessments skills they will need to improve their knowledge and professional
      skills throughout their pharmacy careers.

PMID- 21969719
TI  - A mass merchandiser's role in enhancing pharmacy students' business plan
      development skills for medication therapy management services.
AB  - OBJECTIVES: To develop a relationship between a pharmacy management course and a
      mass merchandiser and to determine whether involving pharmacy managers from the
      mass merchandiser in the course would enhance student skills in developing a
      business plan for medication therapy management services. DESIGN: The pharmacy
      managers from the mass merchandiser participated in lectures, provided panel
      discussions, and conducted a business plan competition. Learning was assessed by
      means of 4 examinations and 1 project (ie, the business plan). At the conclusion
      of the semester, surveys were administered to solicit student input and gain
      insight from pharmacy managers on the perceived value of this portion of the
      course. ASSESSMENT: Students' average grade on the business plan assignment,
      which included the oral presentation, the peer assessment, and the written
      proposal, was 92.2%. Approximately 60% (n=53) of surveyed students agreed or
      strongly agreed that their management skills had improved because of the
      participation of pharmacy managers from the mass merchandiser. All of the
      managers enjoyed participating in the experience. CONCLUSIONS: The involvement of
      pharmacy managers from a mass merchandiser enhanced student learning in the
      classroom, and managers felt that their participation was an important
      contribution to the development of future pharmacists.

PMID- 21969720
TI  - Strengthening pharmaceutical care education in Ethiopia through instructional
      collaboration.
AB  - OBJECTIVE: To describe the development, implementation, and initial outcomes of a
      pharmaceutical care training-of-trainers course developed to assist Ethiopian
      pharmacy faculty members and graduate students in the development of curriculum
      and provision of pharmaceutical care services of relevance to this low-income
      country. DESIGN: In this collaboration, US and Ethiopian faculty members worked
      together in a week-long seminar and in hospital ward rounds to develop and offer
      a course to facilitate faculty members, curricular, and service development in
      pharmaceutical care in Ethiopia. ASSESSMENT: Assessments were conducted during
      the seminar, immediately post-seminar, at 3 months post-seminar, and at 1 year
      post-seminar. An examination was administered at the conclusion of the course to
      assess immediate learning outcomes for the graduate students. Post-course
      assessments of short-term (3-month) and longer-term (12-month) impact were
      conducted to identify pharmaceutical care services that had been implemented to
      assess knowledge and skill gained during the seminar. Correspondence between
      seminar participants and the US faculty members as well as graduate student
      thesis projects provided further evidence of changes at 3 and 12 months post
      course. CONCLUSION: Pharmaceutical care training was developed for Ethiopian
      faculty members through a seminar and hospital ward rounds. Enhancements have
      been added to curricula for bachelor in pharmacy students and select
      pharmaceutical care services have been implemented through master's thesis
      projects.

PMID- 21969721
TI  - Consortium-based approach to an online preceptor development program.
AB  - OBJECTIVE: To describe the implementation process of a consortium-based preceptor
      development program and to review completion and assessment data over the first
      27 months. DESIGN: Five 1-hour, Web-based preceptor development modules were
      developed using streaming media technologies. Modules were released using a
      password-protected Internet site and were free to consortium-affiliated
      preceptors. Preceptor's institutional affiliation, module completion dates,
      module assessments, and continuing education credits were recorded and made
      available to each institution. ASSESSMENT: Three hundred eighty-two preceptors
      completed 1489 modules. Fifty-six percent of preceptors were affiliated with more
      than 1 consortium institution. The number of participating preceptors per
      institution varied from 72 to 204. Sixty-five percent of preceptors completed all
      5 modules. Preceptor satisfaction was high, with 93% agreeing with each course
      evaluation statement. Program cost per institution ranged from $12 to $35 per
      preceptor. CONCLUSIONS: A consortium-based approach to preceptor development is a
      convenient and effective means of providing required training.

PMID- 21969722
TI  - Team-based learning in pharmacotherapeutics.
AB  - OBJECTIVE: To compare student examination performance in pharmacotherapeutics
      before and after implementation of team-based learning. DESIGN: After the
      traditional lecture and workshop method for teaching pharmacotherapeutics was
      replaced with team-based learning in January 2009, students were expected to come
      to class having read assigned chapters in order to successfully complete an
      individual quiz, a group quiz, and group application exercises. ASSESSMENT:
      Student learning was assessed using performance on individual quizzes, group
      quizzes, and the examination at the end of the psychiatry module. Students
      performed as well on the examination at the end of the module as they did prior
      to team-based learning implementation. CONCLUSION: Substituting team-based
      learning for traditional lecture ensured that students prepared for class and
      increased student participation in class discussions.

PMID- 21969723
TI  - A pharmacy political advocacy elective course.
AB  - OBJECTIVE: To develop and implement an elective course to increase pharmacy
      students' awareness of legislation that might affect the pharmacy profession and
      to promote advocacy for the profession. DESIGN: Students participated in class
      discussions regarding current legislative issues and methods to advocate for the
      pharmacy profession. Assignments included a student-led presentation of the
      advocacy agendas for various pharmacy organizations, a take-home examination,
      participation in class debates, and a legislative presentation. ASSESSMENT: Forty
      eight students enrolled in the elective course over 3 years. Assignments and
      class participation were assessed using grading rubrics. At the end of the
      semester, students completed a questionnaire to assess the overall benefit of the
      course. CONCLUSIONS: Participation in an elective course devoted to pharmacy
      political advocacy increased awareness of legislation and the desire to become
      involved in pharmacy organizations to promote the pharmacy profession.

PMID- 21969724
TI  - An elective course to engage pharmacy students in research activities.
AB  - OBJECTIVE: To implement problem-based learning exercises in a pharmacy research
      elective course and assess the impact on students' knowledge and confidence in
      their ability to analyze, design, and present basic research projects relevant to
      clinical areas. DESIGN: Hands-on learning activities, including discussions on
      experimental design, development of collective diagrams, research planning,
      results analysis, data evaluation, and presentation design, were incorporated
      into the course and developed as team-based learning experiences. ASSESSMENT:
      Students gave a seminar presentation to peers and faculty members at the end of
      the semester and created posters for presentations at professional meetings.
      Students who decided to work on a continuation project during the following
      semester were expected to produce data that might be sufficient for the
      development of manuscripts for submission to scientific journals. CONCLUSIONS:
      Feedback from students revealed an appreciation and renewed interest in analyzing
      clinical issues with a much wider focus as well as increased understanding of and
      confidence in using data derived from basic science research.

PMID- 21969725
TI  - Teaching the pharmacology of antiarrhythmic drugs.
AB  - OBJECTIVE: To provide doctor of pharmacy (PharmD) students with highly
      integrated, comprehensive and up-to-date instruction related to the pharmacology
      of antiarrhythmic drugs. DESIGN: Students were taught the medicinal chemistry,
      pharmacology, and therapeutics of antiarrhythmic agents in the cardiology module
      presented in quarter 7 of the PharmD curriculum. Important foundational
      information for this topic was presented to students in prerequisite physiology
      courses and pathophysiology courses offered earlier in the curriculum. Emphasis
      was placed on student critical thinking and active involvement. Weekly recitation
      sessions afforded students the opportunity to apply the information they learned
      regarding arrhythmia pharmacotherapy to comprehensive patient cases. ASSESSMENT:
      Student comprehension was measured using class exercises, short quizzes, case
      write-ups, comprehensive examinations, group exercises, and classroom discussion.
      Students were afforded the opportunity to evaluate the course, and the
      instructors as well as rate the degree to which the course achieved its
      educational outcomes. CONCLUSION: Students learned about cardiac arrhythmias
      through a high-quality, interdisciplinary series of classes presented by faculty
      members with extensive experience related to the pharmacology and pharmacotherapy
      of cardiac arrhythmias.

PMID- 21969726
TI  - Educating for safety in the pharmacy curriculum.
AB  - This overview of the Educating for Safety supplement issue explores the context
      and urgency of the problem of unsafe care, what we have learned about improving
      both safety and quality in health care, and the implications of this for
      educators. This supplement issue is a response to the charge of the AACP Council
      of Deans (COD) and the Council of Faculties (COF) Medication Safety Task Force to
      address the role of colleges and schools of pharmacy in responding to the
      national patient safety agenda. The articles included are intended to serve as a
      nexus for pharmacy education in developing curricula and promoting best practices
      as they relate to the importance of medication safety.

PMID- 21969727
TI  - The science of safety curriculum in US colleges and schools of pharmacy.
AB  - OBJECTIVE: To describe the integration of science of safety (SoS) topics in
      doctor of pharmacy (PharmD) curricula of US colleges and schools of pharmacy.
      METHODS: A questionnaire that contained items pertaining to what and how SoS
      topics are taught in PharmD curricula was e-mailed to representatives at 107 US
      colleges and schools of pharmacy. RESULTS: The majority of the colleges and
      schools responding indicated that they had integrated SoS topics into their
      curriculum, however, some gaps (eg, teaching students about communicating risk,
      Food and Drug Administration [FDA] Sentinel Initiative, utilizing patient
      databases) were identified that need to be addressed. CONCLUSIONS: The FDA and
      the American Association of Colleges of Pharmacy (AACP) should continue to
      collaborate to develop resources needed to ensure that topics proposed by the FDA
      in their SoS framework are taught at all colleges and schools of pharmacy.

PMID- 21969728
TI  - Perspectives on educating pharmacy students about the science of safety.
AB  - OBJECTIVE: To identify opinions about pharmacy graduates' science of safety (SoS)
      educational needs. METHODS: Semi-structured interviews were performed with 25
      educators and researchers at US pharmacy colleges and schools and 5 individuals
      from associations engaged in drug safety-related issues. RESULTS: Themes that
      emerged from the 30 interviews with key informants included: pharmacists should
      meet minimum SoS requirements; medication safety education is inconsistent; and
      barriers exist to improving SoS curricula. Student deficiencies noted included
      the lack of: student acceptance of a "culture of safety": ability to effectively
      communicate verbally about medication safety; knowledge of the drug development
      process; and quality improvement skills. Key informants did not agree on how to
      address these gaps. CONCLUSIONS: While educators, researchers, and other leaders
      in drug safety-related issues thought that US colleges and schools of pharmacy
      covered portions of SoS well, there were perceived deficiencies. Minimum
      standards should be set to assist with curricular adoption of SoS.

PMID- 21969729
TI  - The role of hidden curriculum in teaching pharmacy students about patient safety.
AB  - OBJECTIVE: To examine how hidden and informal curricula shaped pharmacy students'
      learning about patient safety. METHODS: A preliminary study exploring planned
      patient safety content in pharmacy curricula at 3 UK schools of pharmacy was
      conducted. In-depth case studies were then carried out at 2 schools of pharmacy
      to examine patient safety education as delivered. RESULTS: Informal learning from
      teaching practitioners was assigned high levels of credibility by the students,
      indicating the importance of role models in practice. Students felt that the
      hidden lessons received in the form of voluntary work experience compensated for
      limited practice exposure and elements of patient safety not adequately addressed
      in the formal curriculum, such as learning about safe systems, errors, and
      professionalism. CONCLUSIONS: Patient safety is a multifaceted concept and the
      findings from this study highlight the importance of pharmacy students learning
      in a variety of settings to gain an appreciation of these different facets.

PMID- 21969730
TI  - Benefits of interdisciplinary learning between PharmD and PhD students.

PMID- 21969731
TI  - Interprofessional involvement provides educational experience to pharmacy
      students.

PMID- 21969732
TI  - Thumbnail history of pharmacy in the U.S. Army. 1937.

PMID- 21969733
TI  - Testing trivializing maps in the Hybrid Monte Carlo algorithm.
AB  - We test a recent proposal to use approximate trivializing maps in a field theory
      to speed up Hybrid Monte Carlo simulations. Simulating the CPN-1 model, we find a
      small improvement with the leading order transformation, which is however
      compensated by the additional computational overhead. The scaling of the
      algorithm towards the continuum is not changed. In particular, the effect of the
      topological modes on the autocorrelation times is studied.

PMID- 21969734
TI  - A numerical projection technique for large-scale eigenvalue problems.
AB  - We present a new numerical technique to solve large-scale eigenvalue problems. It
      is based on the projection technique, used in strongly correlated quantum many
      body systems, where first an effective approximate model of smaller complexity is
      constructed by projecting out high energy degrees of freedom and in turn solving
      the resulting model by some standard eigenvalue solver.Here we introduce a
      generalization of this idea, where both steps are performed numerically and which
      in contrast to the standard projection technique converges in principle to the
      exact eigenvalues. This approach is not just applicable to eigenvalue problems
      encountered in many-body systems but also in other areas of research that result
      in large-scale eigenvalue problems for matrices which have, roughly speaking,
      mostly a pronounced dominant diagonal part. We will present detailed studies of
      the approach guided by two many-body models.

PMID- 21969735
TI  - HFOLD - A program package for calculating two-body MSSM Higgs decays at full one
      loop level.
AB  - HFOLD (Higgs Full One Loop Decays) is a Fortran program package for calculating
      all MSSM Higgs two-body decay widths and the corresponding branching ratios at
      full one-loop level. The package is done in the SUSY Parameter Analysis
      convention and supports the SUSY Les Houches Accord input and output format. 
      PROGRAM SUMMARY: Program title: HFOLD Catalogue identifier: AEJG_v1_0 Program
      summary URL:http://cpc.cs.qub.ac.uk/summaries/AEJG_v1_0.html Program obtainable
      from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing
      provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html
      No. of lines in distributed program, including test data, etc.: 340 621 No. of
      bytes in distributed program, including test data, etc.: 1 760 051 Distribution
      format: tar.gz Programming language: Fortran 77 Computer: Workstation, PC
      Operating system: Linux RAM: 524 288 000 Bytes Classification: 11.1 External
      routines: LoopTools 2.2 (http://www.feynarts.de/looptools/), SLHALib 2.2
      (http://www.feynarts.de/slha/). The LoopTools code is included in the
      distribution package. Nature of problem: A future high-energy e+e- linear
      collider will be the best environment for the precise measurements of masses,
      cross sections, branching ratios, etc. Experimental accuracies are expected at
      the per-cent down to the per-mile level. These must be matched from the
      theoretical side. Therefore higher order calculations are mandatory. Solution
      method: This program package calculates all MSSM Higgs two-body decay widths and
      the corresponding branching ratios at full one-loop level. The renormalization is
      done in the DR scheme following the SUSY Parameter Analysis convention. The
      program supports the SUSY Les Houches Accord input and output format. Running
      time: The example provided takes only a few seconds to run.

PMID- 21969736
TI  - Could CoRoT-7b and Kepler-10b be remnants of evaporated gas or ice giants?
AB  - We present thermal mass loss calculations over evolutionary time scales for the
      investigation if the smallest transiting rocky exoplanets CoRoT-7b (~1.68REarth)
      and Kepler-10b (~1.416REarth) could be remnants of an initially more massive
      hydrogen-rich gas giant or a hot Neptune-class exoplanet. We apply a thermal mass
      loss formula which yields results that are comparable to hydrodynamic loss
      models. Our approach considers the effect of the Roche lobe, realistic heating
      efficiencies and a radius scaling law derived from observations of hot Jupiters.
      We study the influence of the mean planetary density on the thermal mass loss by
      placing hypothetical exoplanets with the characteristics of Jupiter, Saturn,
      Neptune, and Uranus to the orbital location of CoRoT-7b at 0.017 AU and Kepler
      10b at 0.01684 AU and assuming that these planets orbit a K- or G-type host star.
      Our findings indicate that hydrogen-rich gas giants within the mass domain of
      Saturn or Jupiter cannot thermally lose such an amount of mass that CoRoT-7b and
      Kepler-10b would result in a rocky residue. Moreover, our calculations show that
      the present time mass of both rocky exoplanets can be neither a result of
      evaporation of a hydrogen envelope of a "Hot Neptune" nor a "Hot Uranus"-class
      object. Depending on the initial density and mass, these planets most likely were
      always rocky planets which could lose a thin hydrogen envelope, but not cores of
      thermally evaporated initially much more massive and larger objects.

PMID- 21969737
TI  - The impact of stricter criteria for disability insurance on labor force
      participation.
AB  - This paper studies the effect of a large-scale policy change in the Austrian
      disability insurance program, which tightened eligibility criteria for men above
      a certain age. Using administrative data on the universe of Austrian private
      sector employees, the results of difference-in-difference regressions suggest a
      substantial and statistically significant decline in disability enrollment of 6
      to 7.4 percentage points and an increase in employment of 1.6 to 3.4 percentage
      points. The policy change had important spillover effects into the unemployment
      and sickness insurance program. Specifically, the share of individuals receiving
      unemployment benefits increased by 3.5 to 3.9 percentage points, and the share
      receiving sickness insurance benefits, by roughly 0.7 percentage points.

PMID- 21969739
TI  - Polymers for colon targeted drug delivery.
AB  - The colon targeted drug delivery has a number of important implications in the
      field of pharmacotherapy. Oral colon targeted drug delivery systems have recently
      gained importance for delivering a variety of therapeutic agents for both local
      and systemic administration. Targeting of drugs to the colon via oral
      administration protect the drug from degradation or release in the stomach and
      small intestine. It also ensures abrupt or controlled release of the drug in the
      proximal colon. Various drug delivery systems have been designed that deliver the
      drug quantitatively to the colon and then trigger the release of drug. This
      review will cover different types of polymers which can be used in formulation of
      colon targeted drug delivery systems.

PMID- 21969738
TI  - Nano-vectors for the Ocular Delivery of Nucleic Acid-based Therapeutics.
AB  - Nucleic acid-based therapeutics have gained a lot of interest for the treatment
      of diverse ophthalmic pathologies. The first to enter in clinic has been an
      oligonucleotide, Vitravene((r)) for the treatment of cytomegalovirus infection.
      More recently, research on aptamers for the treatment of age related macular
      degeneration has led to the development of Macugen((r)). Despite intense
      potential, effective ocular delivery of nucleic acids is a major challenge since
      therapeutic targets for nucleic acid-based drugs are mainly located in the
      posterior eye segment, requiring repeated invasive administration. Of late,
      nanotechnology-based nano-vectors have been developed in order to overcome the
      drawbacks of viral and other non-viral vectors. The diversity of nano-vectors
      allows for ease of use, flexibility in application, low-cost of production,
      higher transfection efficiency and enhanced genomic safety. Using nano-vector
      strategies, nucleic acids can be delivered either encapsulated or complexed with
      cationic lipids, polymers or peptides forming sustained release systems, which
      can be tailored according to the ocular tissue being targeted. The present review
      focuses on developments and advances in various nano-vectors for the ocular
      delivery of nucleic acid-based therapeutics, the barriers that such delivery
      systems face and methods to overcome them.

PMID- 21969740
TI  - Evaluation of Antiinflammatory Activity of Centratherum anthelminticum (L) Kuntze
      Seed.
AB  - In the present study petroleum ether and alcoholic extracts of Centratherum
      anthelminticum (L) Kuntze seed (100 mg and 200 mg/kg p.o.) were evaluated for
      antiinflammatory activity in acute and subacute models of inflammation. It was
      found that both petroleum ether and alcoholic extracts showed significant
      reduction in paw oedema in carrageenan-induced model. In subchronic inflammatory
      phase both extracts provoked a significant reduction of transudation phase and
      too little extent proliferative phase when tested in cotton pellet-induced
      granuloma model. Both the extracts also reduced alkaline phosphatase activity in
      serum. The histopathology of granuloma tissue showed significant inhibition of
      lymphocytes, neutrophils, exudates, necrosis and giant cell when compared with
      control without ulcerogenic effect. The results suggest that petroleum ether and
      alcoholic extracts may exert antiinflammatory activity through prostaglandin
      inhibition, reduced myeloperoxidase and antitransudation.

PMID- 21969741
TI  - Formulation and evaluation of trimetazidine dihydrochloride extended release
      tablets by melt congealing method.
AB  - Trimetazidine dihydrochloride, a cellular antiischemic agent indicated in the
      management and prophylaxis of angina pectoris is given as 20 mg thrice daily in
      the conventional dosage regimen. The purpose of the present study was to
      formulate and evaluate twice a day extended release tablets containing 30 mg
      trimetazidine dihydrochloride. The method developed to formulate these extended
      release tablets was melt congealing followed by wet granulation which exhibited
      uniform sustained release action and overcame the drawbacks of multidosing. The
      formulation was developed with Methocel((r)) K100M and stearic acid as release
      retardant.

PMID- 21969742
TI  - Effect of Different Carriers on in vitro Permeation of Meloxicam through Rat
      Skin.
AB  - The ability of beta-cyclodextrin, hydroxypropyl-beta-cyclodextrin, polyvinyl
      pyrrolidone and urea to influence the percutaneous absorption of meloxicam
      through isolated rat skin was evaluated. Carrier complex were prepared by
      kneading method in 1:1 and 1:2 in molar ratios for beta-cyclodextrin and
      hydroxypropyl-beta-cyclodextrin and in 1:1, 1:3 and 1:5 in weight ratios for
      polyvinyl pyrrolidone and urea. The complexes were characterized by IR, DSC and
      evaluated for solubility, dissolution and skin permeability. The solubility,
      dissolution and permeability of meloxicam were enhanced by using the carriers.
      The influence of cyclodextrins, polyvinyl pyrrolidone and urea on in vitro
      permeation of meloxicam through rat skin was investigated by incorporation of
      prepared carrier complex in 1% carbopol gel. The prepared gel was evaluated for
      drug content, pH and viscosity and in vitro permeation. All the percutaneous
      parameters like flux (Jss), amount permeated (Q(6)), diffusivity (D),
      permeability coefficient (K(p)), partition coefficient (K) and release rate
      constant (k) were calculated statistically. In vitro permeation study showed the
      trend that the penetration flux and enhancement factor increases with increasing
      concentration of beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin and then
      decrease dramatically in case of hydroxypropyl-beta-cyclodextrin gel formulation
      with the increase to 1:2 ratio. Similar changes in pattern of permeation were
      also observed with polyvinyl pyrrolidone and urea carrier complex. These findings
      concluded that the carriers cyclodextrins, polyvinyl pyrrolidone and urea could
      be used as transdermal permeation enhancer in topical preparation of meloxicam.

PMID- 21969743
TI  - Synthesis and anticonvulsant activity of a new series of 1,4-dihydropyridine
      derivatives.
AB  - A series of 1,4-dihydropyridine derivatives (1a-g) were prepared from three
      compounds condensation of Hantzsch synthesis. A new series of 2,2'-{[4-(aryl)-2,6
      dimethyl-1,4-dihydropyridine-3,5-diyl]dicarbonyl}dihydrazinecarbothioamide (2a-g)
      were prepared from compounds diethyl 4-(aryl)-2,6-dimethyl-1,4-dihydropyridine
      3,5-dicarboxylate (1a-g) reacted with thiosemicarbazide to give the corresponding
      compounds (2a-g) by hydrazinolysis method. The synthesized compounds were
      confirmed by IR, (1)HNMR, (13)CNMR, mass spectral and elemental analyses. The
      newly synthesized compounds (2a-g) were screened for anticonvulsant activity
      against in swiss albino rat. The test was evaluated by maximal electrode induced
      convulsion method. Synthesized compounds were used two (50 and 100 mg/kg)
      concentrations. Compounds (1a-g) were inactive while compounds (2a-g) have
      moderate anti-convulsant activity compared with standard phenytoin drug. The
      compound 2,2'-{[4-(furan-2-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5
      diyl]dicarbonyl} dihydrazinecarbothioamide (2a) has highly active compared with
      other compound (2b-2g).

PMID- 21969744
TI  - Determination of actarit from human plasma for bioequivalence studies.
AB  - An analytical method based on high-performance liquid chromatography with
      ultraviolet detection (245 nm) was developed for the determination of actarit in
      human plasma. Coumarin was used as an internal standard. Chromatographic
      separation was achieved with a C8 column using a mobile phase of methanol: 1%
      acetic acid (50-50, v/v) with a flow rate of 1.0 ml/min. The calibration curve
      was linear over the range of 0.1-4.0 MUg/ml (r(2) > 0.99) and the lower limit of
      quantification was 0.1 MUg/ml. The method was validated for sensitivity,
      accuracy, precision, recovery and stability. The method was used to determine the
      concentration-time profiles of actarit in the plasma following oral
      administration of 100 mg actarit tablets.

PMID- 21969745
TI  - Montmorillonite-Alginate Composites as a Drug delivery System: Intercalation and
      In vitro Release of Diclofenac sodium.
AB  - Diclofenac sodium and alginate was intercalated into montmorillonite to form
      uniform sized beads by gelation method. The structure and surface morphology of
      the synthesized composite beads were characterized by powdered X-ray diffraction,
      Fourier transform infrared spectroscopy, thermo gravimetric analysis and scanning
      electron microscopy. Diclofenac release kinetics of the composite in simulated
      intestinal fluid medium (pH 7.4) and effect of montmorillonite content on the in
      vitro release of diclofenac from diclofenac-montmorillonite-alginate composites
      bead was investigated by UV/Vis spectrophotometer. Diclofenac encapsulation
      efficiency in the montmorillonite-alginate composites bead increases with an
      increase in the montmorillonite content. The control release of diclofenac from
      diclofenac-montmorillonite-alginate composites beads was observed to be better as
      compared to diclofenac-alginate beads.

PMID- 21969746
TI  - Formulation and evaluation of floating drug delivery system of famotidine.
AB  - A multiple unit oral floating drug delivery system of famotidine was developed to
      prolong gastric residence time, target stomach mucosa and increase drug
      bioavailability. Drug and polymer compatibility was studied by subjecting
      physical mixtures of drug and polymers to differential scanning calorimetry. Cod
      liver oil entrapped calcium alginate beads containing famotidine, capable of
      floating in the gastric condition were formulated and evaluated. The gel beads
      were prepared by emulsion gelation method by employing sodium alginate alone and
      mixture of sodium alginate and hydrophilic copolymers such as carbopol 934P and
      hydroxypropylmethylcellulose K15M grade in three different ratios. The effect of
      selected factors, such as percentage of oil and amount of copolymers on floating
      properties was investigated. The beads were evaluated for percent drug loading,
      drug entrapment efficiency, buoyancy and in vitro drug release. The in vitro drug
      release study of the beads was carried out in simulated gastric media employing a
      modified Rosette-Rice test apparatus. Wherein, the apparatus was further modified
      by incorporating a water jacket to the apparatus to circulate hot water to
      maintain 37+/-2 degrees  for throughout the release study. All the oil entrapped
      calcium alginate beads floated if a sufficient amount of oil was used. Beads
      formulated employing sodium alginate alone could not sustain the drug release up
      to 8 h, whereas beads formulated with mixture of sodium alginate and copolymers
      demonstrated sustained release of famotidine up to 8 h. The results suggested
      that cod liver oil entrapped calcium alginate beads were promising as a carrier
      for intragastric floating drug delivery of famotidine.

PMID- 21969747
TI  - Role of Mitochondrial Enzymes and Sarcoplasmic ATPase in Cardioprotection
      Mediated by Aqueous Extract of Desmodium gangeticum (L) DC Root on Ischemic
      Reperfusion Injury.
AB  - The present study investigate the protective effect of aqueous root extract of
      Desmodium gangeticum in preserving mitochondrial and sarcoplasmic ATPase during
      ischemia reperfusion injury. The isolated rat hearts in both drug and control
      group were subjected to warm ischemia (37 degrees ), followed by reperfusion with
      the Langendorff perfusion system. The aqueous root extract of Desmodium
      gangeticum (L) at a dose of 50 mg/kg body weight was found to be effective in the
      rat heart for the management of ischemic reperfusion injury. Physiological
      parameters were significantly (P<0.05) improved in drug treated rat hearts.
      Creatine phosphokinase in coronary perfusate found to be declined. Moreover,
      sarcoplasmic ATPase and mitochondrial enzymes were significantly (P<0.05)
      improved in drug treated rat hearts. In fact, histological analysis of the
      myocardium also suggested an improved ultra structure in Desmodium gangeticum
      treated rat heart. These results suggest that Desmodium gangeticum aqueous root
      extract can preserve the mitochondrial and sarcoplasmic ATPase in the myocardium,
      resulting in the improvement of cardiac function after ischemia reperfusion
      injury.

PMID- 21969748
TI  - Development and Validation of a Simple Isocratic HPLC Method for Simultaneous
      Estimation of Phytosterols in Cissus quadrangularis.
AB  - Cissus quadrangularis L. is a promising remedy prescribed in the ancient
      Ayurvedic literature for bone fracture healing properties. As this activity has
      been extensively investigated and well established, a range of formulations
      containing C. quadrangularis has been marketed. This work reports the development
      and validation of a reliable RP-HPLC method for the analysis of phytosterols in
      the various extracts of the plant. The proposed method utilizes a Cosmosil C(8)
      column (250 ? 4.6 mm) with a compatible Phenomenex C(8) guard column with
      isocratic elution of acetonitrile and water (95:5 v/v) at 25 degrees . An
      effluent flow rate of 2 ml/min and UV detection at 202 nm was used for the
      analysis of phytosterols. The described method was linear in the range of 1-500
      MUg/ml, with excellent correlation coefficients. The precision, robustness and
      ruggedness values were also within the prescribed limits (less than 2%). The
      recovery values were within the range, which indicates that the accuracy of the
      analysis was good and that the interference of the matrix with the recovery of
      phytosterols was low. The phytosterols were found to be stable in a stock
      solution for 48 h (% RSD was below 2%) and no interfering extra peaks were
      observed under controlled stress conditions. The proposed method is simple,
      specific, precise, accurate, and reproducible and thus can be used for routine
      analysis of C. quadrangularis phytosterols in quality control laboratories.

PMID- 21969749
TI  - Hepatoprotective Effects and Safety Evaluation of Coumarinolignoids Isolated from
      Cleome viscosa Seeds.
AB  - The aim of the present work was to investigate the in vivo hepatoprotective
      potential of coumarinolignoids (cleomiscosins A, B, and C) isolated from the
      seeds of C. viscosa. The study was performed against CCl(4)-induced
      hepatotoxicity in albino rats. Rats were divided into four groups. The animals of
      group I served as normal and was given only vehicle. Group II served as toxin
      control and administered with CCl(4) (50% solution liquid paraffin, 2 ml/kg
      intraperitoneally). The animals of group III received coumarinolignoids (50
      mg/kg) for six days orally as well as CCl(4) (2 ml/kg) on 4(th) day i.p.
      Similarly animals of group IV received silymarin (50 mg/kg) for six days orally
      as well as CCl(4) on 4(th) day i.p. On 7(th) day various parameters viz. serum
      glutamyl oxaloacetic transaminase, serum glutamyl pyruvate transaminase, serum
      alkaline phosphatase, serum bilirubin, liver glycogen were estimated and
      histopathology was performed. Additionally, acute oral toxicity of the said
      coumarinolignoids was carried out in swiss albino mice. The coumarinolignoids
      were found to be effective as hepatoprotective against CCl(4)-induced
      hepatotoxicity as evidenced by in vivo and histopathological studies in small
      animals. Safety evaluation studies also exhibit that coumarinolignoids are well
      tolerated by small animals in acute oral toxicity study except minor changes in
      red blood cell count and hepatic protein content at 5000 mg/kg body weight as a
      single oral dose. Coumarinolignoids which is the mixture of three compounds
      (cleomiscosin A, B and C) is showing the significant protective effects against
      CCl(4)-induced hepatotoxicity in small animals and also coumarinolignoids are
      well tolerated by small animals in acute oral study.

PMID- 21969750
TI  - Synthesis of thiolated alginate and evaluation of mucoadhesiveness, cytotoxicity
      and release retardant properties.
AB  - Modification of polymers by covalent attachment of thiol bearing pendant groups
      is reported to impart many beneficial properties to them. Hence in the present
      study, sodium alginate-cysteine conjugate was synthesized by carbodiimide
      mediated coupling under varying reaction conditions and the derivatives
      characterized for thiol content. The thiolated alginate species synthesized had
      bound thiol content ranging from 247.8+/-11.03-324.54+/-10.107 ?mol/g of polymer
      depending on the reaction conditions. Matrix tablets based on sodium alginate
      cysteine conjugate and native sodium alginate containing tramadol hydrochloride
      as a model drug were prepared and mucoadhesive strength and in vitro drug release
      from the tablets were compared. Tablets containing 75 mg sodium alginate-cysteine
      conjugate could sustain release of 10 mg of model drug for 3 h, whereas 90% of
      the drug was released within 1 h from corresponding tablets prepared using native
      sodium alginate. An approximately 2-fold increase in the minimal detachment force
      of the tablets from an artificial mucin film was observed for sodium alginate
      cysteine conjugate as compared to native sodium alginate. In vitro cytotoxicity
      studies in L-929 mouse fibroblast cells studied using an MTT assay revealed that
      at low concentrations of polymer, sodium alginate-cysteine conjugate was less
      toxic to L-929 mouse fibroblast cell line when compared to native sodium
      alginate. Hence, thiolation is found to be a simple route to improving polymer
      performance. The combination of improved controlled drug release and mucoadhesive
      properties coupled with the low toxicity of these new excipients builds up
      immense scope for the use of thiolated polymers in mucoadhesive drug delivery
      systems.

PMID- 21969751
TI  - Influence of Some Heavy Metals on Growth, Alkaloid Content and Composition in
      Catharanthus roseus L.
AB  - Shoot biomass production, alkaloid content and composition as influence by
      cadmium, manganese, nickel and lead at uniform dose of 5 mM were investigated in
      Catharanthus roseus plants grown in sand culture. Treatment with Mn, Ni, and Pb
      significantly enhanced total root alkaloid accumulation. Cd and Ni treatment
      resulted in two-fold where as Pb treatment resulted in three fold increase in
      serpentine content of roots. The non-significant affect on biomass suggests that
      plants can withstand metal stress at the level tested with positive affect on
      root alkaloid content.

PMID- 21969752
TI  - Synthesis, in vitro and in vivo antifungal activity of 5-phenylthio-2,4
      bisbenzyloxypyrimidine: a novel nucleobase.
AB  - A pyrimidne nucleobase, 5-phenylthio-2,4-bisbenzyloxypyrimidine and its analogs
      were synthesized and scanned for in vitro antifungal activity using cup-plate and
      macrobroth dilution method against Candida albicans, Aspergillus niger,
      Aspergillus flavus and Aspergllus fumigatus. In the cup-plate method, 5
      phenylthio-2,4-bisbenzyloxypyrimidine showed very good antifungal activity
      compared to clotrimazole at the concentrations of 100 and 1000 MUg/ml and in the
      macrobroth dilution method, it showed comparable activity with respect to
      standard drugs fluconazole and itraconaole. In vivo antifungal activity of 5
      phenylthio-2,4-bisbenzyloxypyrimidine at the dose levels of 10 and 30 mg/kg was
      carried by causing systemic infection of mice using the same fungi used in in
      vitro testing. The results from in vivo studies with 5-phenylthio-2,4
      bisbenzyloxypyrimidine and fluconazole indicated that 5-phenylthio-2,4
      bisbenzyloxypyrimidine had similar potency as fluconazole at both dose levels.

PMID- 21969753
TI  - Stability-Indicating RP-HPLC Method for Estimation of Miglitol in Bulk and
      Tablets.
AB  - A selective and sensitive, stability-indicating reverse phase high performance
      liquid chromatography method has been first developed and validated for the
      estimation of miglitol in bulk and tablet dosages form. Samples were separated on
      a prepacked, Inertsil amino C(18) column (150*4.6 mm i.d.) using a mobile phase
      comprised of acetonitrile and monobasic sodium phosphate pH 7.5 (80:20, v/v)
      delivered at 1.5 ml/min flow rate. Detection was performed on a SPD-20A
      prominence UV/Vis detector at 220 nm. The retention time for miglitol was 13.93+/
      0.0367. The method was validated in terms of linearity, precision, accuracy,
      ruggedness, and specificity, limit of detection and limit of quantification. The
      linearity (r(2)) and percentage recoveries of miglitol were 0.9986 and 99.85%.
      This method is suitable for routine estimation of miglitol in bulk and tablet
      dosages form.

PMID- 21969754
TI  - RP - HPLC method for the estimation of Tamsulosin Hydrochloride in Tablet Dosage
      Form.
AB  - A rapid and sensitive reverse phase RP-HPLC method is proposed for the estimation
      of tamsulosin hydrochloride in tablets. Tamsulosin hydrochloride was
      chromatographed on a reverse phase C18 column with a mobile phase consisting of
      acetonitrile and water in the ratio of 50:50 v/v. The mobile phase was pumped at
      a flow rate of 1.5 ml/min. The eluents were monitored at 214 nm. The retention
      time of the drug was 1.7 min. With this method, linearity was observed between
      area under curve and concentration of tamsulosin hydrochloride in the injected
      solution, in the range of 5 to 100 MUg/ml. The method was found to be applicable
      for analysis of the drug in tablets. The results were validated statistically.

PMID- 21969755
TI  - Prospective observational evaluation of incidences and implications of drug-drug
      interactions induced adverse drug reactions in critically ill patients.
AB  - The primary aim of this study is to identify and analyze the importance of
      adverse drug reaction due to drug-drug interaction as a contributing factor
      towards drug safety. Patients more than 18 years of age admitted in
      multidisciplinary intensive care unit of a tertiary care hospital were included
      in this study. Patients who stayed less than 48 h and patients in whom all
      treatment modalities have been withdrawn and were on comfort measures only (no
      drugs were prescribed), were excluded. All the drugs that were given during
      intensive care unit stay were checked for presence of potential interactions
      which led to adverse drug reaction. Drug-drug interactions that were detected
      clinically or through investigations were recorded and also any therapeutic
      actions taken for drug-drug interactions were noted. From June 2006 to April
      2007, 400 patients-prescriptions were analyzed. Adverse drug reactions due to
      drug-drug interactions were identified in 64% patients. Among those patients
      38.67% had a single drug-drug interaction. Potential drug-drug interactions were
      602. Clinically significant drug-drug interactions among the potential were 208
      (34.55%). Clinically relevant drug-drug interactions were 103 (49.52% of 208
      episodes). The adverse drug reactions due to drug-drug interactions in our sample
      were managed either by substituting another drug (50.48% of 103 episodes) or by
      adjusting the dose (1% of 103 episodes) or by omitting the drug (48.54% of 103
      episodes). Among the 208 observed drug-drug interactions induced adverse drug
      reactions 21.63% was severe drug-drug interactions induced adverse drug
      reactions, 23.08% was moderate drug-drug interactions induced adverse drug
      reactions and 55.29% was minor drug-drug interactions induced adverse drug
      reactions. The interactions which were life threatening and/ or require medical
      intervention to minimize or prevent serious adverse effects were considered as
      severe drug-drug interactions and those interaction which resulted in an
      exacerbation of the patient's condition and/ or require an alteration in therapy
      were considered as moderate drug-drug interactions. The interactions which were
      limited clinical effects and manifestations may include an increase in the
      frequency or severity of side effects but generally would not require a major
      alteration in therapy were classified as minor drug-drug interactions. The
      correlation coefficient was 0.86 between the number of drugs given to the patient
      & number of average potential adverse drug reactions found among the patients.
      Increase in number of prescribed drug significantly (one way) increases number of
      potential adverse drug reaction due to drug-drug interaction (p<0.0001).
      Critically ill patients are more susceptible to drug-drug interactions due to the
      administration of multiple drugs and complex drug combinations. Several drug-drug
      interactions were clinically irrelevant.

PMID- 21969756
TI  - A method for content uniformity determination of atenolol and losartan potassium
      in combined tablet dosage form.
AB  - A simple, accurate, rapid, specific and reproducible UV spectrophotometric method
      was developed for estimation of content uniformity of atenolol and losartan
      potassium in its combined tablet dosage form. The method involves formation and
      solving the simultaneous equation using 226.4 and 254 nm as two wavelengths for
      atenolol and losartan, respectively. Developed method was employed to determine
      the atenolol and losartan content in ten individual tablet units of five market
      formulations. Methanol was used as solvent. The method was validated. From the
      results, it was concluded that all brands are within the content uniformity
      limit, 85-115%.

PMID- 21969757
TI  - Antioxidant Effect of Tinospora cordifolia Extract in Alloxan-induced Diabetic
      Rats.
AB  - Many plants are claimed to possess antidiabetic and antioxidant activity. In
      practice, it is being increasingly recognized to be an alternative approach to
      modern medicine. This study assess the antioxidant capacity of Tinospora
      cordifolia stem methanol extract in daily oral administration of 500 mg/kg of
      body weight for 40 days in alloxan induced diabetic rats. The erythrocytes
      membrane lipid peroxide and catalase activity was increased where as the
      activities of superoxide dismutase, glutathione peroxidase were found to be
      decreased significantly (P<0.01) in alloxan-induced diabetic rats. The levels of
      lipid peroxide in liver of diabetic rats increased significantly (P<0.01) and
      catalase, superoxide dismutase, glutathione peroxidase in liver was significantly
      decreased in alloxan-induced diabetic rats, when compared to normal rats. After
      treatment of methanol Tinospora cordifolia stem extract brings back to normal
      (P<0.01) in the erythrocytes membrane and liver cell enzymes activities.

PMID- 21969758
TI  - Development and Validation of HPTLC Method for the Estimation of Rizatriptan
      Benzoate in Bulk and Tablets.
AB  - A new, simple high performance thin layer chromatographic method has been
      proposed for the determination of rizatriptan benzoate in a tablet dosage form.
      The drug was separated on aluminum plates precoated with silica gel 60 F(254)
      with dichloromethane-acetone-acetic acid 3:2:0.2(v/v/v) as mobilephase.
      Quantitative analysis was performed by densitometric scanning at 230 nm. The
      method was validated for linearity, accuracy, precision and robustness. The
      calibration plot was linear over the range 200-700 ng/band for rizatriptan
      benzoate. The method was successfully applied to the analysis of drug in bulk and
      marketed tablets.

PMID- 21969759
TI  - Synthesis and Biological Evaluation of Chalcones having Heterosubstituent(s).
AB  - Chalcones and their synthetic analogues appear to have the same binding site of
      tubuline as phenstatin, combretastatin steganacin and podophylotoxin and are
      therefore capable to inhibit cancer cell proliferation. The phenyl rings with
      appropriate substitutions maintain a fixed distance between two centers of aryl
      rings. The two aromatic rings in these molecules are arranged like the two wings
      of a butterfly having certain dihedral angle between them, therefore a "butterfly
      model" is proposed an important structural feature responsible for their
      antitubulin activity. In this sequence a series of chalcones were synthesized and
      evaluated for in vitro cytotoxic activity against a panel of human cancer cell
      lines. In addition the synthetics reduced MIC of ciprofloxacin upto four fold
      this indicates their bioavailability enhancing potential.

PMID- 21969760
TI  - Synthesis, Antiviral and Cytotoxic Activities of 2-(2-Phenyl carboxylic acid)-3
      Phenylquinazolin -4(3H)-one Derivatives.
AB  - A series of novel 2,3-disubstitutedquinazolin-4(3H)-ones have been synthesized by
      condensation of 2-substituted benzo[1,3]oxazine-4-ones and anthranilic acid.
      Synthesized compounds were evaluated for in vitro antiviral activity against HIV,
      HSV and vaccinia viruses. 5-Bromo-2-(6-bromo-4-oxo-2-phenyl-4H-quinazolin-3-yl)
      benzoic acid (MBR2) exhibited distinct antiviral activity against Herpes simplex
      and vaccinia viruses.

PMID- 21969761
TI  - Determination of 1,7,7-Trimethyl-bicyclo(2,2,1)heptan-2-one in a Cream
      Pharmaceutical Formulation by Reversed-phase Liquid Chromatography.
AB  - A reversed-phase liquid chromatographic method for the determination of 1,7,7
      trimethyl-bicyclo(2,2,1)heptan-2-one in a cream formulation is developed and
      validated. The separation was achieved using an isocratic mobile phase, on a
      Lichrosorb C8 column. The calibration curve is linear (r(2)= 0.9999) from 25-175%
      of the analytical concentration of 1.0 mg/ml. The mean percent standard deviation
      values for intra-day and inter-day precision studies were <1%. The recovery
      ranges 99.80-100.06% from a cream formulation. The method can be used reliably in
      quality control for the analysis of bulk cream samples and final product release.

PMID- 21969762
TI  - Development and validation of an ultra performance liquid chromatography method
      for venlafaxine hydrochloride in bulk and capsule dosage form.
AB  - A simple, specific, accurate, and precise ultra performance liquid
      chromatographic method was developed and validated for the estimation of
      venlafaxine hydrochloride in tablet dosage forms. A acquity TM BEH column having
      C18, 100*2.1 mm i.d. in isocratic mode, with mobile phase containing dipotassium
      hydrogen phosphate: Acetonitrile (30:70 v/v; pH 7.00 with dilute o-phosphoric
      acid) was used. The flow rate was 0.75 ml/min and effluents were monitored at 227
      nm. The retention time of venlafaxine hydrochloride was 0.548 min. The method was
      validated for specificity, linearity, accuracy, precision, limit of
      quantification, limit of detection, robustness and solution stability. Limit of
      detection and limit of quantification for estimation of venlafaxine hydrochloride
      were found to be 6.11 MUg/ml and 20.33 MUg/ml, respectively. Recoveries of
      venlafaxine hydrochloride in tablet formulations were found to be in the range of
      99.3-99.5%. Proposed method was successfully applied for the quantitative
      determination of venlafaxine hydrochloride in tablet dosage forms.

PMID- 21969763
TI  - In Vitro Antibacterial and Antifungal Properties of Aqueous and Non-Aqueous Frond
      Extracts of Psilotum nudum, Nephrolepis biserrata and Nephrolepis cordifolia.
AB  - Plants are an important source of neutraceuticals that have proved to be
      effective against important microbial infections of humans. Lower plants are
      gaining importance in this regard. The present study is aimed at investigating
      the antimicrobial properties of three selected ferns, Psilotum nudum, Nephrolepis
      biserrata and Nephrolepis cordifolia. The aerial parts of the selected ferns, P.
      nudum, N. biserrata and N. cordifolia, were fractionated in different solvents.
      These fractions were concentrated to obtain a powder and were tested against nine
      bacterial and three fungal strains according to disc diffusion method. The water
      and ethanol fractions were active against most of the tested bacterial and fungal
      strains, some of these were more effective than the controls tested. Present
      study suggests that the pteridophytes, P. nudum, N. biserrata and N. cordifolia
      could be good source of antimicrobials. These natural compounds might be more
      effective as the microbes may have lesser chance of developing resistant mutants.

PMID- 21969764
TI  - In vitro evaluation of domperidone mouth dissolving tablets.
AB  - In the present research work mouth dissolving tablets of domperidone were
      developed with superdisintegrants like crospovidone, croscarmellose sodium and
      sodium starch glycollate in various concentrations like 3%, 4% and 6% w/w by
      direct compression method. All formulations were evaluated for physical
      characteristics of compressed tablets such as weight variation, hardness,
      friability, content uniformity, in vitro disintegration time, wetting time and in
      vitro dissolution study. Among all, the formulation F3 (containing 6% w/w
      concentration of crospovidone) was considered to be the best formulation, having
      disintegration time of 9 s, wetting time of 15 s and in vitro drug release of
      99.22% in 15 min.

PMID- 21969765
TI  - Quantitative analysis of clopidogrel bisulphate and aspirin by first derivative
      spectrophotometric method in tablets.
AB  - A simple, accurate and precise spectrophotometric method has been developed for
      simultaneous estimation of clopidogrel bisulphate and aspirin by employing first
      order derivative zero crossing method. The first order derivative absorption at
      232.5 nm (zero cross point of aspirin) was used for clopidogrel bisulphate and
      211.3 nm (zero cross point of clopidogrel bisulphate) for aspirin.Both the drugs
      obeyed linearity in the concentration range of 5.0 MUg/ml to 25.0 MUg/ml
      (correlation coefficient r(2)<1). No interference was found between both
      determined constituents and those of matrix. The method was validated
      statistically and recovery studies were carried out to confirm the accuracy of
      the method.

PMID- 21969766
TI  - Use Your Words: The Role of Language in the Development of Toddlers' Self
      Regulation.
AB  - Self-regulation emerges throughout early childhood, and predicts later success in
      socially and cognitively challenging situations. Vygotsky proposed that symbols,
      particularly words, serve as mental tools to be used in service of self
      regulation. Cross-sectional research indicates a positive but inconsistent
      association between language and self-regulation skills throughout toddlerhood,
      but research has not accounted for general cognitive development, nor gender
      differences in these domains. We used growth modeling of longitudinal data for
      120 toddlers collected when children were 14, 24, and 36 months to test the
      impact of two expressive language skills - spoken vocabulary and talkativeness -
      on the growth of toddlers' self-regulation, and to determine whether associations
      between these domains exist when controlling for cognitive development. Results
      reveal gender differences in self-regulation trajectories, and in the impact of
      language on self-regulation. Vocabulary is a better predictor of self-regulation
      than talkativeness, and both concurrent and prior vocabulary positively predicted
      children's levels of self-regulation. When cognitive development was controlled,
      24-month vocabulary still predicted the trajectory of self-regulation. Results
      reveal that, even in early development, words are tools that can be applied to
      the task of self-regulation, and may be a more necessary tool for boys than for
      girls at this age.

PMID- 21969767
TI  - Enhancing the Transition to Kindergarten: A Randomized Trial to Test the Efficacy
      of the "Stars" Summer Kindergarten Orientation Program.
AB  - This randomized trial tested the efficacy of an intensive, four-week summer
      program designed to enhance low-income children's transition to kindergarten (n's
      = 60 program children, 40 controls). Administered in four public schools, the
      program focused on social competence, pre-literacy and pre-numeracy skills,
      school routines, and parental involvement. Hierarchical linear modeling indicated
      that the program significantly improved teachers' ratings of (a) the transition
      to the social aspect of kindergarten for girls (but not boys); and (b) the
      transition to kindergarten routines for the subgroup of children who had the same
      teacher for kindergarten as for the summer program. Findings are discussed in
      terms of practices and policies for supporting children's transition to school.

PMID- 21969768
TI  - Intraperitoneal oxygen/ozone treatment decreases the formation of experimental
      postsurgical peritoneal adhesions and the levels/activity of the local ubiquitin
      proteasome system.
AB  - We have investigated whether an oxygen/ozone (95%O2/5%O3) mixture would have
      potential against the formation of experimental postsurgical peritoneal
      adhesions. In two groups of rats, one control intraperitoneally injected with 3
      mL/rat of O2 and one intraperitoneally injected with oxygen/ozone mixture (3
      mL/rat equivalent to 300 MUg/kg ozone), we induced a midline laparotomy and an
      enterotomy at the level of the ileum to encourage the formation of peritoneal
      adhesions. Samples were taken from the parietal peritoneal tissue to assess the
      formation of adhesions 0 and 10 days after the surgical procedure and to assess
      the levels of ubiquitin and 20S proteasome. We found decreased formation of
      postsurgical peritoneal adhesions after treatment of the rats with 300 MUg/kg
      ozone associated with a decreased levels of ubiquitin and 20S proteasome subunit
      within the adhered tissue. Oxygen/ozone mixture is potentially useful for
      approaching the post-surgical peritoneal adhesions, and the UPS system is
      involved in this.

PMID- 21969769
TI  - Preschool Depression: The Importance of Identification of Depression Early in
      Development.
AB  - The empirical finding that school-aged children could suffer clinical depression
      refuted the widely held assumption that this age group would be too
      developmentally immature to experience depressive symptoms. Currently childhood
      depression is a well-recognized and widely treated clinical disorder. Following
      more recent developmental findings emphasizing the emotional sophistication of
      very young children, scientific studies have demonstrated that depression can
      arise early in life, during the preschool period of development. Preschool
      depression is characterized by typical symptoms of depression such as anhedonia;
      changes in sleep, appetite, and activity level; and excessive guilt. Further,
      longitudinal continuity of preschool depression into school age has been
      established, suggesting that preschool depression is an early manifestation of
      the later childhood disorder. Based on the known efficacy of early developmental
      intervention in a number of domains and disorders related to the greater
      neuroplasticity of the brain earlier rather than later in childhood, it is
      important to identify depression at the earliest possible point. Early
      intervention strategies for preschool depression that focus on enhancing
      emotional development are currently being tested.

PMID- 21969770
TI  - Emergency nuclear medicine.

PMID- 21969771
TI  - Dual-time-point positron emission tomography findings of benign mediastinal
      fluorine-18-fluorodeoxyglucose uptake in tuberculosis-endemic region.
AB  - BACKGROUND: We performed dual-time-point positron emission tomography imaging in
      patients without evidences of mediastinal lymph node metastasis to investigate
      the characteristics of benign mediastinal fluorine-18-fluorodeoxyglucose (FDG)
      uptake. MATERIALS AND METHODS: One-hundred and eighteen mediastinal lesions of 24
      patients were included for this study. On the early and delayed positron emission
      tomography images, size, attenuation, maximum standardized uptake value (SUV) and
      retention indices (RI) were recorded for lymph node characterization. RESULTS:
      The mean SUV on the early and delayed scan of 118 lymph nodes was 3.3+/-1.2 and
      4.2+/-1.7, respectively. The mean RI was 26.4+/-24.5%. Higher FDG uptake was
      observed in patients with calcified nodules and bilateral FDG uptake and in lymph
      nodes with calcification or short-axis diameter larger than 10 mm. CONCLUSION: In
      tuberculosis-endemic area, the increments of SUV or RI were frequently observed
      in benign mediastinal lymph nodes, and these values might not be the accurate
      indicators of malignant disease for mediastinal FDG uptake.

PMID- 21969772
TI  - Prevalence of myocardial perfusion abnormalities in end-stage liver disease.
AB  - BACKGROUND: The prevalence of coronary artery disease (CAD) in end-stage liver
      disease (ESLD) being evaluated for orthotopic liver transplantation (OLT) is
      unclear based on variable definition used for CAD. OBJECTIVE: The aim of this
      study to investigate the prevalence of abnormal stress myocardial perfusion
      single-photon emission computed tomography (MPS) imaging, as a marker for CAD,
      among patients with ESLD who were referred for stress MPS imaging as a routine
      work up before OLT. MATERIALS AND METHODS: This was a single-center,
      retrospective study. We reviewed data on 167 patients who were referred for MPS
      as a routine work up before OLT over the last 2 years. All patients underwent
      evaluation for CAD risk factors [age, hypercholesterolemia, diabetes mellitus
      (DM), hypertension (HTN), and smoking], and stress MPS as per standard protocol.
      RESULTS: The total number of patients referred for stress MPS was 167. Seven
      patients (4% of total study population) were excluded from the study due to poor
      and/or nondiagnostic studies. 147 patients (92%) had normal, but only 13 patients
      (8%) had abnormal MPS scans. DM and male gender were the most independent risk
      factors for abnormal MPS with P value of 0.046, and 0.26, respectively. There was
      no significant association between the abnormal MPS result and HTN,
      hypercholesterolemia, smoking, age or etiology of the liver disease. CONCLUSION:
      Based on our data, the prevalence of abnormal MPS and left ventricular ejection
      fraction in patients with ESLD was found to be 8%. DM and male gender were the
      most independent predictor factors for abnormal MPS. True prevalence of CAD and
      usefulness of MPS in patients with ESLD can only be studied using a very large
      and randomized prospective study.

PMID- 21969773
TI  - Estimation of radiation dose received by the radiation worker during F-18 FDG
      injection process.
AB  - BACKGROUND: The radiation dosimetric literature concerning the medical and non
      medical personnel working in nuclear medicine departments are limited,
      particularly radiation doses received by radiation worker in nuclear medicine
      department during positron emission tomography (PET) radiopharmaceutical
      injection process. This is of interest and concern for the personnel. AIM: To
      measure the radiation dose received by the staff involved in injection process of
      Fluorine-18 Fluorodeoxyglucose (FDG). MATERIALS AND METHODS: The effective whole
      body doses to the radiation workers involved in injections of 1511 patients over
      a period of 10 weeks were evaluated using pocket dosimeter. Each patient was
      injected with 5 MBq/kg of F-18 FDG. The F18-FDG injection protocol followed in
      our department is as follows. The technologist dispenses the dose to be injected
      and records the pre-injection activity. The nursing staff members then secure an
      intravenous catheter. The nuclear medicine physicians/residents inject the dose
      on a rotation basis in accordance with ALARA principle. After the injection of
      the tracer, the nursing staff members flush the intravenous catheter. The person
      who injected the tracer then measures the post-injection residual dose in the
      syringe. RESULTS: THE MEAN EFFECTIVE WHOLE BODY DOSES PER INJECTION FOR THE STAFF
      WERE THE FOLLOWING: Nurses received 1.44+/-0.22 MUSv/injection (3.71+/-0.48
      nSv/MBq), for doctors the dose values were 2.44+/-0.25 MUSv/injection (6.29+/
      0.49 nSv/MBq) and for technologists the doses were 0.61+/-0.10 MUSv/injection
      (1.58+/-0.21 nSv/MBq). It was seen that the mean effective whole body dose per
      injection of our positron emission tomography/computed tomography (PET/CT) staff
      who were involved in the F18-FDG injection process was maximum for doctors
      (54.34% differential doses), followed by nurses (32.02% differential doses) and
      technologist (13.64% differential doses). CONCLUSION: This study confirms that
      low levels of radiation dose are received by staff during F18-FDG injection and
      these values can be used as a reference to allay any anxiety in the radiation
      workers.

PMID- 21969774
TI  - A study to improve the image quality in low-dose computed tomography (SPECT)
      using filtration.
AB  - BACKGROUND: The output of the X-ray tube used in computed tomography (CT)
      provides a spectrum of photon energies. Low-energy photons are preferentially
      absorbed in tissue; the beam spectrum shifts toward the higher energy end as it
      passes through more tissue, thereby changing its effective attenuation
      coefficient and producing a variety of artifacts (beam-hardening effects) in
      images. Filtering of the beam may be used to remove low-energy photon component.
      The accuracy of attenuation coefficient calculation by bilinear model depends
      highly upon accuracy of Hounsfield units. Therefore, we have made an attempt to
      minimize the beam-hardening effects using additional copper filter in the X-ray
      beam. The quantitative evaluation were made to see the effect of additional
      filters on resulting CT images. MATERIALS AND METHODS: This study was performed
      on dual-head SPECT (HAWKEYE 4, GE Healthcare) with low-dose CT which acquires
      images at peak voltages of 120/140 kV and a tube current of 2.5 mA. For the
      evaluation of image quality, we used CT QA Phantom (PHILIPS) having six different
      density pins of Water, Polyethylene, Nylon (Aculon), Lexan, Acrylic (Perspex) and
      Teflon. The axial images were acquired using copper filters of various
      thicknesses ranging from 1 to 5 mm in steps of 1 mm. The copper filter was
      designed in such a manner that it fits exactly on the collimator cover of CT X
      ray tube. Appropriate fixation of the copper filter was ensured before starting
      the image acquisition. As our intention was only to see the effect of beam
      hardening on the attenuation map, no SPECT study was performed. First set of
      images was acquired without putting any filter into the beam. Then, successively,
      filters of different thicknesses were placed into the beam and calibration of the
      CT scanner was performed before acquiring the images. The X-ray tube parameters
      were kept the same as that of unfiltered X-ray beam. All the acquired image sets
      were displayed using Xeleris 2 (GE Healthcare) on a high-resolution monitor.
      Moreover, Jaszak's SPECT Phantom after removing the spheres was used to see the
      different contrast intensities by inserting the different contrast materials of
      iodine and bismuth in water as background media. Images were analyzed for
      visibility, spatial resolution and contrast. RESULTS: Successive improvement in
      the image quality was noticed when we increased the filter thickness from 1 to 3
      mm. The images acquired with 3-mm filter appeared almost with no artifacts and
      were visibly sharper. Lower energy photons from X-ray beam cause a number of
      artifacts, especially at bone-tissue interfaces. Additional filtrations removed
      lower energy photons and improved the image quality. Degradation in the image
      quality was noticed when we increased the filter thickness further to 4 and 5 mm.
      This degradation in image quality happened due to reduced photon flux of the
      resulting X-ray beam, causing high statistical noise. The spatial resolution for
      image matrix of 512 * 512 was found to be 1.29, 1.07, 0.64 and 0.54 mm for
      without filter, with 1, 2 and 3 mm filters, respectively. The image quality was
      further analyzed for signal-to-noise ratio (SNR). It was found to be 1.72, 1.78,
      1.98 and 1.99 for open, with 1, 2 and 3 mm filters respectively. This shows that
      3-mm filter results in an improvement of 15.7% in SNR. CONCLUSION: On the basis
      of this study, we could conclude that use of 3-mm copper filter in the X-ray beam
      is optimal for removing the artifacts without causing any significant reduction
      in the photon flux of the resulting X-ray beam. We also propose that as artifacts
      have been removed from the images, the value of Hounsfield units will be more
      accurate and hence the value of attenuation coefficients lead to better contrast
      and visualization of SPECT images.

PMID- 21969775
TI  - Size-dependent thresholding as an optimal method for tumor volume delineation on
      positron emission tomography-computed tomography: A Phantom study.
AB  - BACKGROUND: Use of a fixed threshold value for tumor volume delineation in
      positron emission tomography (PET) images will ignore the effect of size of the
      lesion and source to background ratio (SBR). The purpose of this Phantom study
      was to evaluate the effect of the size of the lesion and SBR on the threshold to
      be used for PET tumor volume delineation. MATERIALS AND METHODS: Phantom used in
      the study comprised a sphere-cylinder assembly containing six spheres of
      different inner diameters (1.10, 1.35, 1.44, 1.50, 1.83 and 1.93 cm) with inner
      volumes of 0.70, 1.30, 1.50, 1.77, 3.22 and 3.82 cm(3), respectively. The scans
      were acquired with SBR of 6:01, 7:01, 8:01 and 10:01. These SBRs were calculated
      from 42 patients with lymphoma to simulate clinical images. PET tumor volume was
      calculated using RT_Image software at different threshold values (40, 45, 50, 55,
      60, 65, 70 and 75% of SUV(max)) for each sphere at different SBRs. The threshold
      intensity value at which the calculated volume was nearly equal to actual volume
      of spheres was considered as the standardized threshold intensity (STI) value.
      RESULTS: STI values depended on the diameter of the sphere and not on the SBR. It
      is found that 40% threshold is suitable for calculating the volume of any lesion
      with diameter greater than 1.83 cm, 60% for diameter greater than 1.35 cm but
      less than 1.83 cm, and 75% for diameter less than 1.35 cm. CONCLUSION: Size
      dependent thresholding is an accurate and reproducible method of tumor volume
      delineation on PET-computed tomography (CT).

PMID- 21969776
TI  - Subcutaneous fatty tissue metastasis from renal cell carcinoma detected with
      fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography
      and magnetic resonance imaging.
AB  - A patient who had undergone left radical nephrectomy 11 years ago for renal cell
      carcinoma (RCC) was referred to our clinic for restaging. Fluorine-18
      fluorodeoxyglucose (F18-FDG) positron emission tomography/computed tomography
      (F18-FDG PET/CT) showed hypometabolic area in left frontal region of the brain
      and increased FDG uptake in the subcutaneous fatty tissues of the right thigh.
      Histopathological examination of the biopsy material from the left frontal region
      and right gluteal region revealed metastasis of clear cell type RCC. Seven months
      later, a magnetic resonance imaging (MRI) of right cruris showed a contrast
      enhancing lesion with a diameter of 3.5 cm, located at the subcutaneous area of
      posterior part of right cruris. A concomitant F18-FDG PET/CT detected an
      increased FDG uptake focus in the proximal third of right cruris adjacent to the
      muscle planes and this finding was consistent with metastasis of RCC.

PMID- 21969777
TI  - F-18 Fluorodeoxyglucose positron emission tomography/computed tomography in
      tuberculosis of the hip: A case report and brief review of literature.
AB  - Tuberculosis (TB) has become a global health concern. Cross-sectional imaging
      modalities like ultrasound, computed tomography and magnetic resonance imaging
      play an important role in the diagnosis, assessment of disease extent and
      response to treatment. PET/CT, a unique molecular imaging technique, allows the
      most accurate correlation of anatomic and metabolic information. We report a case
      wherein PET/CT played a significant role and contributed valuable information in
      the evaluation of a patient with TB of the hip. A brief review of the existing
      literature on the role of PET/CT in musculoskeletal TB is also discussed.

PMID- 21969778
TI  - Incidental detection of clinically occult follicle stimulating hormone secreting
      pituitary adenoma on whole body 18-Fluorodeoxyglucose positron emission
      tomography-computed tomography.
AB  - A 73-year-old man, known case of Hodgkin's lymphoma, underwent 18
      Fluorodeoxyglucose positron emission tomography-computed tomography (18-FDG PET
      CT) for post-chemotherapy evaluation of the disease status. The scan revealed
      focal increased FDG uptake in pituitary fossa. The CT images showed homogenously
      enhancing pituitary lesion causing expansion of the sella. A possibility for the
      presence of pituitary adenoma was raised in the report. Hormonal assay of the
      patient showed raised follicle stimulating hormone (FSH) level of 18 IU/ml
      (normal range for males up to 5 IU/ml). All the other pituitary hormones were
      within the normal range. Nuclear magnetic resonance (NMR) imaging of brain showed
      a pituitary lesion with expanded sella pushing the optic chiasma superiorly. NMR
      findings confirmed the presence of pituitary macroadenoma. A final diagnosis of
      FSH secreting pituitary macroadenoma was made.

PMID- 21969779
TI  - Ribbing disease: Uncommon cause of a common symptom.
AB  - Ribbing disease is a rare form of sclerosing dysplasia characterized by benign
      endosteal and periosteal bone growth confined to the diaphyses of the long bones,
      usually the tibiae and femora. It occurs after puberty and is more commonly seen
      in women. The most common presenting symptom is pain that is usually self
      limited; however, progression is known. The etiology and optimal treatment for
      the disease are as yet undefined. We present here the case of a 31-year-old woman
      with clinical, radiological and bone scan manifestations of Ribbing disease
      corroborated by bone biopsy. Radiographs demonstrated cortical thickening of the
      diaphyses of both tibiae. 99mTc-methylene diphosphonate bone scan revealed
      intense irregular uptake in diaphyseal region of both tibiae. Magnetic resonance
      imaging showed cortical thickening with bone marrow edema in bilateral tibial
      diaphysis with minimal adjacent soft tissue edema. Bone biopsy revealed
      predominantly dense lamellar bone with irregular sized and spaced haversian
      systems. Serum and urine markers of bone metabolism were within normal limits.
      The patient was treated with analgesics, and had partial relief from pain.
      Medullary rimming is the next treatment option in case pain progresses. This
      report emphasizes the role of bone scan in the diagnosis of this rare condition.

PMID- 21969780
TI  - An interesting case of polyostotic fibrous dysplasia: The "pirate sign" evaluated
      with Tc-99m methylene diphosphonate single-photon emission computed
      tomography/computerized tomography.
AB  - Polyostotic fibrous dysplasia is a rare progressive benign disorder of the bone.
      Bone scintigraphy is extremely useful in the initial evaluation for identifying
      the extent of disease. We report a case presenting with pathological fracture of
      the shaft of the right femur. After treatment of the fracture, bone scintigraphy
      revealed involvement of multiple bones including the skull and facial bones. The
      utility of single-photon emission computed tomography/computerized tomography in
      the evaluation of the extent of skull base involvement is highlighted.

PMID- 21969781
TI  - Urinary bladder carcinoma associated with Paget's disease of skull: Imaging
      findings on Tc99m-MDP bone scintigraphy, F18-Fluoride PET/CT and F18-FDG PET/CT.
AB  - We report the imaging findings of a patient with Paget's disease in metastatic
      carcinoma bladder evaluated by Tc99m-Methylene diphosphonate (MDP) bone
      scintigraphy, F18-Fluoride positron emission tomography/computed tomography
      (PET/CT) and F18-fluorodeoxy glucose (FDG) PET/CT. Tc99m-MDP bone scan showed
      intense uptake in the skull bones without any other abnormal tracer distribution.
      F18-Fluoride PET/CT revealed intense uptake in the pelvic bones along with skull
      bones, but F18-FDG PET/CT showed intense multifocal FDG uptake in the bladder and
      bilateral inguinal lymph nodes, with no abnormal uptake in the skull bones. CT
      images showed thickening of skull bones.

PMID- 21969782
TI  - Tc99m-MDP bone scintigraphy in Engelmann-Camurati disease.
AB  - Engelmann-Camurati disease (ECD) is a rare bone disorder characterized by
      autosomal dominant inheritance. It usually presents in early childhood and is
      associated with symmetrical diaphyseal sclerosis. We report a 20-year-old female
      with scintigraphic findings characteristic of ECD. She was treated with
      corticosteroids and showed marked clinical improvement.

PMID- 21969783
TI  - Tc-99m MDP bone scintigraphy in a case of Touraine-Solente-Gole syndrome.
AB  - Pachydermoperiostosis is a form of primary hypertrophic osteoarthropathy, also
      known as Touraine-Solente-Gole syndrome. It is a rare disease. In this report, we
      present the case of a 29-year-old man with this rare disorder, having significant
      findings on Tc-99m methylene diphosphonate bone scan.

PMID- 21969784
TI  - Vertebral hemangioma: "Cold" vertebrae on bone scintigraphy and fluordeoxy
      glucose positron emission tomography-computed tomography.
AB  - Bone hemangiomas are benign and infrequent lesions. At Tc-99m bone scintigraphy
      they show variable degrees of radiotracer uptake and even absence of it. At
      fluordeoxy-glucose (FDG) Positron Emission Tomography-Computed Tomography
      (PET/CT), hemangioma is one of the causes of "cold" vertebrae, apart from
      postexternal radiotherapy. We present a woman diagnosed of breast carcinoma, with
      a photopenic defect at a thoracic vertebrae at Tc-99m bone scan. In order to rule
      out bone lytic metastasis, a FDG PET/CT was performed showing a "cold" vertebrae
      too. Findings were highly suggestive of vertebral hemangioma, that was confirmed
      by magnetic resonance imaging.

PMID- 21969785
TI  - Spectrum of single photon emission computed tomography/computed tomography
      findings in patients with parathyroid adenomas.
AB  - Primary hyperparathyroidism results from excessive parathyroid hormone secretion.
      Approximately 85% of all cases of primary hyperparathyroidism are caused by a
      single parathyroid adenoma; 10-15% of the cases are caused by parathyroid
      hyperplasia. Parathyroid carcinoma accounts for approximately 3-4% of cases of
      primary disease. Technetium-99m-sestamibi (MIBI), the current scintigraphic
      procedure of choice for preoperative parathyroid localization, can be performed
      in various ways. The "single-isotope, double-phase technique" is based on the
      fact that MIBI washes out more rapidly from the thyroid than from abnormal
      parathyroid tissue. However, not all parathyroid lesions retain MIBI and not all
      thyroid tissue washes out quickly, and subtraction imaging is helpful. Single
      photon emission computed tomography (SPECT) provides information for localizing
      parathyroid lesions, differentiating thyroid from parathyroid lesions, and
      detecting and localizing ectopic parathyroid lesions. Addition of CT with SPECT
      improves the sensitivity. This pictorial assay demonstrates various SPECT/CT
      patterns observed in parathyroid scintigraphy.

PMID- 21969786
TI  - Nuclear denotation: A topic for global public health concern.

PMID- 21969787
TI  - Screening and analysis of the multiple absorbed bioactive components and
      metabolites of Baihe Zhimu Tang by the metabolic fingerprinting technique and
      liquid chromatography/diode array detection-electrospray ionization-mass
      spectrometry.
AB  - BACKGROUND: Baihe Zhimu Tang (BZT) is a widely used traditional Chinese medicinal
      formula in treating various diseases; however, its active components have
      remained unknown. MATERIALS AND METHODS: Based on the metabolic fingerprinting
      technique and liquid chromatography/diode array detection-electrospray ionization
      mass spectrometry (LC/DAD-ESI-MS), a method for rapid screening and analysis of
      the multiple absorbed bioactive components and metabolites of an oral solution of
      Baihe Zhimu Tang (BZT) in rabbit plasma, urine and feces after oral
      administration of BZT was developed. RESULTS: The results obtained from a
      comprehensive comparative analysis of the fingerprints of the BZT and its
      metabolic fingerprints in rabbit biological samples indicated that 19 components
      in the BZT were absorbed into the rabbit's body. Both of them were tentatively
      identified from their MS and UV spectra and retention behaviors by comparing the
      results with the reported literature. In addition, only six components were found
      in the metabolic fingerprints, which suggested that they might be metabolites of
      some components in the BZT. CONCLUSION: The findings demonstrated that the
      proposed method could be used to rapidly and simultaneously analyze and screen
      the multiple absorbed bioactive constituents and metabolites in a formula of
      traditional Chinese medicines (TCMs) by comparing and contrasting the
      chromatographic fingerprints with its metabolic fingerprints. This is very
      important not only for the pharmaceutical discovery process and the quality
      control of crude drugs, but also for explaining the curative mechanism of TCMs.

PMID- 21969788
TI  - Optimization of extraction process and investigation of antioxidant effect of
      polysaccharides from the root of Limonium sinense Kuntze.
AB  - OBJECTIVE: To optimize the extraction technology for polysaccharides from the
      root of Limonium sinense (Girard) Kuntze, Plumbaginaceae and evaluate the
      antioxidant capacity of polysaccharides from L. sinense (LSEP)  MATERIALS AND
      METHODS: One-singer factor and response surface methodology(RSM) were established
      to extract the polysaccharides from L. sinense. Then, the 1,1-diphenyl-2
      picrylhydrazyl free radical, hydroxyl radical(.OH), and 2,2'-Azino-bis-(3
      ethylbenzothiazoline-6-sulfonic acid) diammonium salt free radical assays were
      established to measure the antioxidant capacity of the LSEP in vitro. RESULTS:
      According to analysis, extraction temperature significantly affected extraction
      yield. The optimum extraction conditions for LSEP were as follows: extraction
      temperature, 95 degrees C; ultrasonic time 50 minutes; and dosage liquor ratio,
      1: 12. Under these conditions, the experimental yield of crude LSEP was 12.80+/
      0.19% which was well matched with the predicted models. The antioxidant capacity
      data suggested that LSEP has strong antioxidant activity. CONCLUSION: One-singer
      factor and RSM were used to extract of LSEP are simple and feasible and LSEP
      could be developed as a nutraceutical agent for itsstrong antioxidant activity.

PMID- 21969789
TI  - Evaluation of phytochemical composition and antioxidant capacity of a decoction
      containing Adenanthera pavonina L. and Thespesia populnea L.
AB  - BACKGROUND: A decoction prepared with barks of Adenanthera pavonina and Thespesia
      populnea is a herbal formulation which has been prescribed in Sri Lanka in the
      treatment of cancer patients for many years. This study was designed to
      investigate its phytochemical and antioxidant properties. MATERIALS AND METHODS:
      The total phenolics and flavonoids were determined using Folin-Ciocalteau and
      aluminum chloride colorimetric methods, respectively. Gallic acid content in the
      decoction was determined using high-performance liquid chromatography. The
      antioxidant properties were evaluated by 1, 1-diphenyl-2-picrylhydrazyl (DPPH)
      radical assay, nitric oxide scavenging assay, deoxyribose method, and the
      reducing power of the decoction. RESULTS: The concentration of total phenols,
      flavonoids, and gallic acid of the decoction were 34.13 +/- 3.54 w/w % gallic
      acid equivalents, 41.37 +/- 0.57 w/w % of (-)-Epigallocatechin gallate
      equivalents, and 0.58 +/- 0.24 mg/g, respectively. The EC50 for DPPH, nitric
      oxide scavenging, and deoxyribose assays were 7.24 +/- 0.50, 14.02 +/- 0.66, and
      53.21 +/- 2.82 MUg/ml, respectively. Reducing power of the decoction increased
      with the concentration. CONCLUSION: These investigations suggested that the
      decoction prepared with A. pavonina and T. populnea can be a potential source of
      nutraceuticals with antioxidant activity.

PMID- 21969790
TI  - Generation of autotetraploid plant of ginger (Zingiber officinale Rosc.) and its
      quality evaluation.
AB  - BACKGROUND: Zingiber officinale Rosc. is not only an important medical plant in
      China, but also one of the most commonly used plant spices around the world.
      Early researches in Z. officinale Rosc. were focused on rapid propagation,
      germplasm preservation, and somatic embryogenesis, only a few reports focused on
      the generation of tetraploid ginger plants with colchicines treatment in vitro.
      MATERIALS AND METHODS: The adventitious buds were submerged into different
      concentrations of colchicine water solution for different time to induce
      polyploid plants, and the induced buds were identified by root-tip chromosome
      determination and stomatal apparatus observation. Eighteen selected tetraploid
      lines were transferred to the field, and the leaf characteristics, rhizome yield,
      contents of volatile oil and gingerol were respectively evaluated to provide
      evidence of high-yield and good qualities of tetraploid ginger. RESULTS: The
      induction rate reached as high as 33.3% of treated buds. More than 48 lines of
      autotetraploid plants were obtained. All tetraploid plants showed typical
      polyploidy characteristics. All of the 18 selected tetraploid lines possessed
      higher rhizome yield and overall productivity of volatile oil and gingerol than
      those of the control. CONCLUSION: Five elite lines have been selected for further
      selection and breeding new varieties for commercial production in agricultural
      production.

PMID- 21969791
TI  - The alteration of components in the fermented Hwangryunhaedok-tang and its
      neuroprotective activity.
AB  - BACKGROUND: Hwangryunhaedok-tang is a traditional herbal prescription that has
      sedative activity, hypotensive and anti-bacterial effects. OBJECTIVE: In this
      study, we investigated the alteration of contents of components in
      Hwangryunhaedok-tang, antioxidant activity and neuroprotective activity by
      fermentation with Lactobacillus acidophilus KFRI 128. MATERIALS AND METHODS:
      Contents of three marker compounds (geniposide, berberine and palmatine) and
      unknown compounds in the Hwangryunhaedok-tang (HR) and the fermented
      Hwangryunhaedok-tang (FHR) were measured and compared using the established high
      performance liqued chromatograph coupled with a photodiode (HPLC-DAD) method. The
      antioxidant activity of HR and FHR were determined by DPPH free radical and
      hydrogen peroxide (H(2)O(2)) scavenging assay. Also, the neuroprotective
      activities of HR and FHR against glutamate-induced oxidative stress in a mouse
      hippocampal cell line (HT22) were evaluated by MTT assay. RESULTS: The contents
      of geniposide and palmatine were decreased but the content of berberine was
      increased in the FHR. And the contents of unknown compounds (1), (2), (3), (4)
      and (5) in the HR were altered by fermentation. Electron donating activity (EDA,
      %) value of FHR was higher than HR for DPPH radical scavenging activity and H2O2
      scavenging activity, respectively. In the MTT assay, FHR showed more potent
      neuroprotective activity than HR by 513.90%. CONCLUSION: The FHR using
      microorganism could convert compounds in HR and enhance the antioxidant and
      neuroprotective activity.

PMID- 21969793
TI  - Ellagic acid ameliorates lung injury after intestinal ischemia-reperfusion.
AB  - BACKGROUND: The aim of this study was to investigate the possible protective role
      of antioxidant treatment with ellagic acid (EA) on lung injury after intestinal
      ischemia-reperfusion (I/R) injury using biochemical and histopatological
      approaches. MATERIALS AND METHODS: Forty rats were divided into four groups as
      control, control + EA, I/R, and I/R + EA. The control and control + EA groups
      were also anesthetized and subjected to laparotomy, but without clamp
      application. The control + EA and I/R + EA groups were given EA (85 mg/kg) orally
      prior to experiment. The I/R and I/R + EA groups underwent 30 minutes of
      intestinal ischemia and 1 hour of reperfusion. In all groups, serum total
      antioxidant capacity (TAC) and malondialdehyde (MDA) levels were determined. TAC,
      total oxidative status (TOS), and oxidative stress index (OSI) in lung tissue
      were measured. Lung tissue histopathology was also evaluated by light microscopy.
      RESULTS: TAC levels were higher in control, EA, and I/R + EA groups while TOS,
      OSI, and MDA levels were lower in these groups compared with I/R group. Serum MDA
      levels were significantly higher in I/R + EA group than that of control group.
      Lung tissue TAC levels were lower in I/R + EA group while OSI values were higher
      in that groups compared with EA group. Histological tissue damage was milder in
      the EA treatment group than in the I/R group. CONCLUSION: These results suggest
      that EA treatment protected the rats lung tissue against intestinal I/R injury.

PMID- 21969792
TI  - Effects of Hypericum perforatum extract on rat irritable bowel syndrome.
AB  - CONTEXT: In irritable bowel syndrome (IBS), disturbance of bowel motility is
      associated with infiltration of inflammatory mediators and cytokines into the
      intestine, such as neutrophils, myeloperoxidase (MPO), tumor necrosis factor alfa
      (TNF-alpha), and lipid peroxide. AIMS: Regarding promising anti-inflammatory and
      anti-oxidative effects of Hypericum perforatum (HP) extract, besides its anti
      depressant effect, this study was designed to evaluate the effects of HP in an
      experimental model of IBS. SETTINGS AND DESIGN: IBS was induced by a 5-day
      restraint stress in rats. The HP extract was administered by gavage in doses of
      150, 300, and 450 mg/kg for 26 days. Fluoxetine and loperamide were used as
      positive controls. Gastric emptying and small bowel and colon transit, besides
      the levels of TNF-alpha, MPO, lipid peroxidation, and antioxidant power, were
      determined in colon homogenates. STATISTICAL ANALYSIS USED: Data were analyzed by
      one-way ANOVA followed by Tukey's post hoc test for multiple comparisons.
      RESULTS: A significant reduction in small bowel and colonic transit (450 mg/kg),
      TNF-alpha, MPO, and lipid peroxidation and an increase in antioxidant power in
      all HP-treated groups (150, 300, and 450 mg/kg) were seen as compared with the
      control group. Gastric emptying did not alter significantly when compared with
      the control group. Treatment with loperamide (10 mg/kg) significantly inhibited
      gastric emptying and small bowel and colonic transit, while flouxetine (10 mg/kg)
      decreased gastric emptying, TNF-alpha, MPO, and lipid peroxidation and increased
      the antioxidant power of the samples in comparison with the control group.
      CONCLUSIONS: HP diminished the recruitment of inflammatory cells and TNF-alpha
      following restraint stress not in a dose-dependent manner, possibly via
      inhibition of MPO activity and increasing colon antioxidant power, without any
      difference with fluoxetine. The HP extract inhibits small bowel and colonic
      transit acceleration like loperamide but has minimal effect on gastric emptying.

PMID- 21969794
TI  - Hepatoprotective activity of the Phyllanthus species on tert-butyl hydroperoxide
      (t-BH)-induced cytotoxicity in HepG2 cells.
AB  - BACKGROUND: Phyllanthus (Euphorbiaceae) species have long been used in folk
      medicine to treat various pathological conditions including liver diseases. Some
      species of Phyllanthus were found to exhibit hepatoprotective activity against
      drugs or toxins and this property was majorly attributed to phyllanthin and
      hypophyllanthin. In this study, we examined the hepatoprotective activity of five
      different species of Phyllanthus, namely, Phyllanthus amarus, Phyllanthus
      fraternus, Phyllanthus maderaspatensis, Phyllanthus urinaria, and Phyllanthus
      Rotundifolius. The extracts were also evaluated for the presence of key
      phytoconstituents, phyllanthin and hypophyllanthin. MATERIALS AND METHODS: The
      extracts were evaluated for hepatoprotective activity against tert-butyl
      hydroxide (t-BH)-induced cytotoxicity using human hepatocarcinoma cells (HepG2
      cell line). RESULTS: Only P. urinaria and P. maderaspatensis exhibited
      significant hepatoprotective activity as evident from increased cell viability.
      The HPLC profile revealed that except P. amarus, the other extracts did not
      contain phyllanthin and hypophyllanthin. CONCLUSION: P. urinaria and P.
      maderaspatensis demonstrated dose-dependent hepatoprotective activity and hence,
      can provide promising therapeutic interventions against chemical-induced liver
      damage.

PMID- 21969795
TI  - Circadian aspects of hyperthermia in mice induced by Aconitum napellus.
AB  - BACKGROUND: Aconitum napellus (Acn) is used topically to relieve pain, itching
      and inflammation, and internally to reduce febrile states, among others. Any
      circadian time-related consequences of Acn administration are unknown. The
      objective of this study was to explore the effects of two doses of Acn on body
      temperature (BT) of mice treated at six different times over 24 hours. MATERIALS
      AND METHODS: BALB/c female mice were housed in six chambers (six mice each) with
      air temperature 24 +/- 3 degrees C, humidity 60 +/- 4%, and a 12-hours light
      (L)/12-hours dark cycle, but with L-onset staggered by 4 hours between chambers
      so that study at one external test time resulted in six test times (02, 06, 10,
      14, 18 and 22 hours [h] after light onset). Rectal temperature (RT; in  degrees
      C) was measured at baseline (B) and 1 hour after oral treatment with placebo (P)
      or two doses of Acn (6C and 30C, two studies each) in six studies over an 8 day
      span. The difference in RT for each mouse from the respective B + P timepoint
      mean RT was computed following each Acn treatment, and data from each of the six
      studies (original RT and difference from B + P) were analyzed for time-effect by
      analysis of variance (ANOVA) and for circadian rhythm by 24-hour cosine fitting.
      RESULTS: A CIRCADIAN RHYTHM IN RT WAS FOUND AT B AND AFTER P (MEAN: 35.58 degrees
      C vs. 35.69 degrees C; peak: 15:31 h vs. 15:40 h) and after each Acn dose (30C or
      6C). Acn induced hyperthermia and the overall change in BT was rhythmically
      significant for each dose (mean = +1.95 degrees C vs. +1.70 degrees C), with
      greatest hyperthermia observed during the L-span for each dose (peak = 08:56 h
      vs. 05:17 h). CONCLUSION: Acn administered around the clock induced hyperthermia
      overall and in a time-dependent manner, with greatest effects during the resting
      (L) span. Thus, time of day may significantly impact the outcome of Acn and other
      homeopathic treatments and should be considered in determining optimal dosing and
      treatment time(s) in order to increase the desired outcome and decrease undesired
      effects.

PMID- 21969796
TI  - Effect of cleistanthin A and B on adrenergic and cholinergic receptors.
AB  - OBJECTIVE: The aim was to study the in vitro and in silico interactions of
      cleistanthin A and B on the adrenergic and cholinergic receptors using isolated
      animal tissues and bioinformatics tools. MATERIALS AND METHODS: The alpha
      adrenergic receptor activities of cleistanthin A and B were studied in vitro
      using a guinea pig vas deferens preparation. The beta adrenergic receptor
      activities of cleistanthin A and B on an isolated rat heart were studied in vitro
      using a modified Langendorff apparatus. The effects of cleistanthin A and B on
      the nicotinic and muscarinic cholinergic receptors were studied in vitro using
      rabbit vas deferens and rabbit jejunum, respectively. All the drug responses were
      recorded using a data acquisition system through a variable force transducer. The
      receptor-ligand interactions of cleistanthin A and B with adrenergic and
      cholinergic receptor proteins were determined using the ArgusLab molecular
      modeling and drug docking program. RESULTS: Cleistanthin A and B significantly
      inhibited the actions of the alpha adrenergic receptor and the nicotinic
      cholinergic receptor. Cleistanthin A and B shifted the dose-response curve to the
      right with an increased EC(50) value of phenylephrine and acetylcholine. Both
      cleistanthin A and B did not have any significant effect on the beta adrenergic
      and muscarinic cholinergic receptors. CONCLUSION: Cleistanthin A and B block the
      alpha adrenergic and nicotinic cholinergic receptors, but these compounds do not
      interact at all with the beta adrenergic and muscarinic cholinergic receptors.

PMID- 21969797
TI  - Effects of ethanolic extract of pine needles (Pinus eldarica Medw.) on reserpine
      induced depression-like behavior in male Wistar rats.
AB  - BACKGROUND: In this study, the antidepressant activity of ethanolic extract of
      Pinus eldarica Medw needles was assessed using forced swimming test (FST) in
      rats. MATERIALS AND METHODS: MALE WISTAR RATS WERE RANDOMLY DIVIDED INTO SIX
      GROUPS AND TREATED AS FOLLOWS: first group was received only reserpine (6 mg/kg,
      i.p.), second group was received reserpine (6 mg/kg, i.p.) and imipramine (10
      mg/kg, i.p.), three experimental groups received reserpine (6 mg/kg, i.p.) and
      three doses of pine needle extract (100, 300, and 500 mg/kg, p.o.) respectively
      and the final group (control group) received only vehicle (5% DMSO, i.p.).
      RESULTS: Acute oral administration of ethanolic extract of P. eldarica Medw
      needles at a dosage of 300 mg/kg reduced reserpine-induced increase in immobility
      time in the FST, demonstrating an antidepressant effect in the FST. Additionally,
      extract treatment did not modify the ambulation and rearing evaluated in open
      field test, indicating that antidepressant effect found in the forced swimming
      test was not based on the stimulation of locomotor activity. CONCLUSION: These
      results indicate that ethanolic extract of Pinus eldarica needles possesses an
      antidepressant activity.

PMID- 21969798
TI  - Attenuation of nonenzymatic glycation, hyperglycemia, and hyperlipidemia in
      streptozotocin-induced diabetic rats by chloroform leaf extract of Azadirachta
      indica.
AB  - BACKGROUND: The hypoglycemic effects of hexane, chloroform and methanol extracts
      of leaves of Azadirachta indica (AI) were evaluated by oral administration in
      streptozotocin-induced severe diabetic rats (SD). MATERIALS AND METHODS: The
      effect of chronic oral administration of the extract for 28 days was evaluated in
      streptozotozin diabetic rats. Lipid peroxidation, glycogen content of liver and
      skeletal muscles, insulin, superoxide dismutase (SOD), catalase (CAT),
      glutathione (GSH), oxidized glutathione (GSSG) levels were determined. In
      addition, advanced glycation end product formation (AGEs) was evaluated. RESULTS:
      The most active extracts were obtained with chloroform. Chloroform extract from
      AI shows increased levels of SOD, GSH, GSSG and CAT, hepatic glycogen content,
      glucose-6-phosphatase and insulin plasma levels, which also decreased the
      glucokinase (GK), lipid peroxidation and insulin resistance. The chloroform
      extract exhibited significant inhibitory activity against advanced glycation end
      product formation with an IC(50) average range of 79.1 mg/ml. CONCLUSION:
      Azadirachta indica can improve hyperlipidemia and hyperinsulinema in streptozocin
      induced diabetic rats and, therefore, AI can be potentially considered to be an
      antidiabetic-safe agent.

PMID- 21969799
TI  - Cardiovascular effects of Teucrium polium L. extract in rabbit.
AB  - BACKGROUND: Teucrium polium L. (TP) have been used in herbal medicine for
      different purposes such as antispasmodic, antidiabetic and lowering blood lipid.
      In the present study, the impact of aqueous-ethanol extract of TP on blood
      pressure, heart rate and intraventricular pressure was investigated in rabbit.
      MATERIALS AND METHODS: Twenty-four NWZ rabbits weighed (2-3 kg) were randomly
      divided into four groups. In each experiment, two groups of six rabbits received
      jugular injection of either TP extract (20, 40 and 80 mg/kg) or normal saline for
      blood pressure effects and two groups for intraventricular pressure. Then, blood
      pressure, heart rate and intraventricular pressure were measured via carotid
      cannula using pressure transducer connected to a power lab system, and the data
      were pooled from independent, single-blinded experiments for each group. RESULTS:
      Treatment with 80 mg/kg of TP extract significantly depressed the mean arterial
      blood pressure (12.5%, P< 0.05). However, there was no significant decrease in
      the 20 or 40 mg/kg dose or normal saline treatment group. Moreover, the extract
      increased (dp/dt)max (P<0.05), maximum left ventricular pressure (LVP(max))
      (P<0.05) and decreased (dp/dt)min significantly (P<0.05), there was no meaningful
      effect on left ventricular end-diastolic pressure (LVEDP). CONCLUSION: The
      present results demonstrated the extract had no effect on the heart rate, but
      showed a positive inotropic on the heart and hypotensive effects. These data
      suggested that hypotensive effect may counterbalance by the inotropic effect of
      the extract.

PMID- 21969800
TI  - Honey and renal cell carcinoma.

PMID- 21969801
TI  - Convergence of the Equi-Energy Sampler and Its Application to the Ising Model.
AB  - We provide a complete proof of the convergence of a recently developed sampling
      algorithm called the equi-energy (EE) sampler (Kou, Zhou, and Wong, 2006) in the
      case that the state space is countable. We show that in a countable state space,
      each sampling chain in the EE sampler is strongly ergodic a.s. with the desired
      steady-state distribution. Furthermore, all chains satisfy the individual ergodic
      property. We apply the EE sampler to the Ising model to test its efficiency,
      comparing it with the Metropolis algorithm and the parallel tempering algorithm.
      We observe that the dynamic exponent of the EE sampler is significantly smaller
      than those of parallel tempering and the Metropolis algorithm, demonstrating the
      high efficiency of the EE sampler.

PMID- 21969802
TI  - Determinants of multimethod contraceptive use in a sample of adolescent women
      diagnosed with psychological disorders.
AB  - OBJECTIVE: Despite recommendations for concurrent use of contraceptives and
      condoms to prevent unintended pregnancy and STIs, multimethod contraceptive use
      among women is poor. This study examined individual-, interpersonal-, and
      environmental-level factors that predict multimethod use among sexually active
      adolescent women diagnosed with psychological disorders. METHODS: This multisite
      study analyzed data from 288 sexually active adolescent women who provided
      sociodemographic, psychosocial, and behavioral data related to birth control and
      condom use. RESULTS: 34.7% of the participants reported multimethod use in the
      past three months. Controlling for empirically and theoretically relevant
      covariates, a multivariable logistic regression identified self-efficacy,
      multiple partners, pregnancy history, parental communication, parental norms
      about sex, and neighborhood cohesion as significant predictors of multimethod
      use. CONCLUSIONS: While continued targeted messages about multi-method
      contraceptive use are imperative at the individual level, an uptake in messages
      targeting interpersonal- and environmental-level factors such as adolescents'
      parents and the broader community is urgently needed.

PMID- 21969803
TI  - Microarray analysis for a comprehensive immunological-status evaluation during
      cancer vaccine immune monitoring.
AB  - Anticancer immune responses can be enhanced by immune intervention that promotes
      complex biological mechanisms involving several cellular populations. The
      classical immune monitoring for biological-based cancer clinical trials is often
      based on single-cell analysis. However, the overall effect could be lost by such
      a reductionist approach explaining the lack of correlation among clinical and
      immunological endpoints often reported. Microarray technology could give the
      possibility of studying in a multiparametric setting the immune therapy effects.
      The application of microarray is leading to an improved understanding of the
      immune responses to tumor immunotherapy. In fact, analysis of cancer vaccine
      induced host responses using microarrays is proposed as valuable alternative to
      the standard cell-based methods. This paper shows successful examples of how high
      throughput gene expression profiling contributed to the understanding of
      anticancer immune responses during biological therapy, introducing as well the
      integrative platforms that allow the network analysis in molecular biology
      studies.

PMID- 21969804
TI  - Primary infragenicular angioplasty for diabetic neuroischemic foot ulcers
      following the angiosome distribution: a new paradigm for the vascular
      interventionist?
AB  - The angiosome principle was first described by Jan Taylor in 1987 in the plastic
      reconstructive surgery field, providing useful information on the vascular
      anatomy of the human body. Specifically concerning foot and ankle pathology, it
      may help the clinician to select better vascular access and specific strategies
      for revascularization. This knowledge may be particularly beneficial when
      treating diabetic neuroischemic foot wounds associated with particularly
      aggressive atherosclerotic disease and a poor collateral circulation. The
      implementation of angiosome-based strategies in diabetic infragenicular vascular
      reconstruction may afford encouraging wound healing and limb preservation rates
      using both bypass and endovascular techniques. The minimal invasiveness of these
      novel strategies enables us to perform more specific and more distal tibial
      and/or foot arterial reconstructions, in one or multiple targeted vessels. This
      paper reviews the available literature on this revascularization strategy and
      focuses on the potential benefit of angiosome-guided primary angioplasty for
      diabetic ischemic foot ulcers.

PMID- 21969805
TI  - Treatment of severe diabetic hypoglycemia with glucagon: an underutilized
      therapeutic approach.
AB  - Tight glycemic control is important in reducing and delaying vascular
      complications in type 1 and 2 diabetes patients; however, the benefits achieved
      through strict metabolic control are counterbalanced by an increased risk of
      hypoglycemia. Glucagon is an effective therapy for treating severe hypoglycemia.
      Available as an emergency kit, glucagon is an essential tool for rapid response,
      but remains underappreciated and underused. This article reviews the role of
      glucagon in treating severe hypoglycemia and discusses the need for better
      education on glucagon for people with diabetes and their caregivers in order to
      alleviate fears of hypoglycemia and of administering glucagon in the event of an
      emergency.

PMID- 21969806
TI  - Morning cortisol is lower in obese individuals with normal glucose tolerance.
AB  - BACKGROUND: There is no consensus on the role of cortisol in the pathogenesis of
      obesity and metabolic syndrome (MS). This cross-sectional study aimed to analyze
      the relationship of morning plasma cortisol and adrenocorticotropic hormone
      (ACTH) levels with body mass index (BMI) and glucose tolerance. SUBJECTS AND
      METHODS: The sample frame was the "Offspring of individuals with diabetes study"
      database. A total of 358 offspring of individuals with type 2 diabetes mellitus
      (T2DM) and 287 individuals without a known family history of T2DM were recruited
      for the study. Subjects who were >=10 years of age were selected from the
      database for analysis. Subjects with T2DM were excluded. All participants
      underwent a 75 g oral glucose tolerance test (OGTT), and blood samples were
      collected at 0, 30, 60, and 120 minutes for glucose, insulin and C-peptide.
      Plasma cortisol, ACTH, and lipid profile were estimated from the fasting sample.
      RESULTS: Four hundred and ninety-five participants (305 males [62%] and 190
      females [38%]) were included in the analysis. ACTH and cortisol levels were
      higher in normal-weight subjects than in overweight/obese subjects. Both ACTH and
      cortisol increased as fasting plasma glucose increased. Cortisol levels were
      significantly lower in offspring of T2DM subjects with MS than in offspring of
      T2DM subjects without MS. When adjusted for BMI, the significance was marginal.
      In males, cortisol levels were negatively correlated with early insulin secretion
      during OGTT (insulinogenic index [0-30]) and positively with waist circumference
      and serum high-density lipoprotein cholesterol. In females, fasting glucose and
      systolic blood pressure were significantly and positively correlated. CONCLUSION:
      Body weight was correlated negatively with morning plasma cortisol and ACTH,
      whereas fasting glucose was correlated positively.

PMID- 21969807
TI  - Progression-free survival as a clinical trial endpoint in advanced renal cell
      carcinoma.
AB  - Traditionally, overall survival (os) has been considered the "gold standard" for
      evaluating new systemic oncologic therapies, because death is easy to define, is
      easily compared across disease sites, and is not subject to investigator bias.
      However, as the available options for continuing therapy increase, the use of os
      as a clinical trial endpoint has become problematic because of the increasing
      crossover and contamination of trials. As a result, the approval of promising new
      therapies may be delayed.Many clinicians believe that progression-free survival
      (pfs) is a more viable option for evaluating new therapies in metastatic and
      advanced renal cell carcinoma. As with all endpoints, pfs has inherent biases,
      and those biases must be addressed to ensure that trial results are not
      compromised and that they will be accepted by regulatory authorities. In this
      paper, we examine the issues surrounding the use of pfs as a clinical trial
      endpoint, and we suggest solutions to ensure that data integrity is maintained.

PMID- 21969808
TI  - Progression-free survival in advanced ovarian cancer: a Canadian review and
      expert panel perspective.
AB  - Ovarian cancer is leading cause of gynecologic cancer mortality in Canada. To
      date, overall survival (os) has been the most-used endpoint in oncology trials
      because of its relevance and objectivity. However, as a result of various
      factors, including the pattern of sequential salvage therapies, measurement of os
      and collection of os data are becoming particularly challenging. Phase ii and iii
      trials have therefore adopted progression-free survival (pfs) as a more
      convenient surrogate endpoint; however, the clinical significance of pfs remains
      unclear. This position paper presents discussion topics and findings from a pan
      Canadian meeting of experts that set out to evaluate the relevance of pfs as a
      valid endpoint in ovarian cancer;reach a Canadian consensus on the relevance of
      pfs in ovarian cancer; andtry to address how pfs translates into clinical benefit
      in ovarian cancer.Overall, the findings and the group consensus posit that future
      studies should ensure that trials are designed to evaluate pfs, os, and other
      clinically relevant endpoints such as disease-related symptoms or quality of
      life;incorporate interim futility analyses intended to stop accrual early when
      the experimental regimen is not active;stop trials early to declare superiority
      only when compelling evidence suggests that a new treatment provides benefit for
      a pre-specified, clinically relevant endpoint such as os or symptom relief;
      anddiscourage early release of secondary endpoint results when such a release
      might increase the frequency of crossover to the experimental intervention.

PMID- 21969809
TI  - The significance of progression-free survival as an endpoint in evaluating the
      therapeutic value of antineoplastic agents.

PMID- 21969810
TI  - Progression-free survival as a primary endpoint in clinical trials of metastatic
      colorectal cancer.
AB  - In recent years, significant advances have been made in the management of
      metastatic colorectal cancer. Traditionally, an improvement in overall survival
      has been considered the "gold standard"-the most convincing measure of efficacy.
      However, overall survival requires larger patient numbers and longer follow-up
      and may often be confounded by other factors, including subsequent therapies and
      crossover. Given the number of active therapies for potential investigation,
      demand for rapid evaluation and early availability of new therapies is growing.
      Progression-free survival is regarded as an important measure of treatment
      benefit and, compared with overall survival, can be evaluated earlier, with fewer
      patients and no confounding by subsequent lines of therapy. The present paper
      reviews the advantages, limitations, and relevance of progression-free survival
      as a primary endpoint in randomized trials of metastatic colorectal cancer.

PMID- 21969811
TI  - G-DOC: a systems medicine platform for personalized oncology.
AB  - Currently, cancer therapy remains limited by a "one-size-fits-all" approach,
      whereby treatment decisions are based mainly on the clinical stage of disease,
      yet fail to reference the individual's underlying biology and its role driving
      malignancy. Identifying better personalized therapies for cancer treatment is
      hindered by the lack of high-quality "omics" data of sufficient size to produce
      meaningful results and the ability to integrate biomedical data from disparate
      technologies. Resolving these issues will help translation of therapies from
      research to clinic by helping clinicians develop patient-specific treatments
      based on the unique signatures of patient's tumor. Here we describe the
      Georgetown Database of Cancer (G-DOC), a Web platform that enables basic and
      clinical research by integrating patient characteristics and clinical outcome
      data with a variety of high-throughput research data in a unified environment.
      While several rich data repositories for high-dimensional research data exist in
      the public domain, most focus on a single-data type and do not support
      integration across multiple technologies. Currently, G-DOC contains data from
      more than 2500 breast cancer patients and 800 gastrointestinal cancer patients, G
      DOC includes a broad collection of bioinformatics and systems biology tools for
      analysis and visualization of four major "omics" types: DNA, mRNA, microRNA, and
      metabolites. We believe that G-DOC will help facilitate systems medicine by
      providing identification of trends and patterns in integrated data sets and hence
      facilitate the use of better targeted therapies for cancer. A set of
      representative usage scenarios is provided to highlight the technical
      capabilities of this resource.

PMID- 21969812
TI  - Invasion precedes tumor mass formation in a malignant brain tumor model of
      genetically modified neural stem cells.
AB  - Invasiveness, cellular atypia, and proliferation are hallmarks of malignant
      gliomas. To effectively target each of these characteristics, it is important to
      understand their sequence during tumorigenesis. However, because most gliomas are
      diagnosed at an advanced stage, the chronology of gliomagenesis milestones is not
      well understood. The aim of the present study was to determine the onset of these
      characteristics during tumor development. Brain tumor-initiating cells (BTICs)
      were established by overexpressing H-Ras(V12) in normal neural stem/progenitor
      cells isolated from the subventricular zone of adult mice harboring a homozygous
      deletion of the Ink4a/Arf locus. High-grade malignant brain tumors were then
      created by orthotopic implantation of 10(5) BTICs into the forebrain of 6-week
      old wild-type mice. Micewere killed every week for 5 weeks, and tumors were
      assessed for cellular atypia, proliferation, hemorrhage, necrosis, and invasion.
      All mice developed highly invasive, hypervascular glioblastoma-like tumors. A
      100% penetrance rate and a 4-week median survival were achieved. Tumor cell
      migration along fiber tracts started within days after implantation and was
      followed by perivascular infiltration of tumor cells with marked recruitment of
      reactive host cells. Next, cellular atypia became prominent. Finally, mass
      proliferation and necrosis were observed in the last stage of the disease. Video
      monitoring of BTICs in live brain slices confirmed the early onset of migration,
      as well as the main cell migration patterns. Our results showed that perivascular
      and intraparenchymal tumor cell migration precede tumor mass formation in the
      adult brain, suggesting the need for an early and sustained anti-invasion
      therapy.

PMID- 21969813
TI  - Cox2 and beta-catenin/T-cell factor signaling intestinalize human esophageal
      keratinocytes when cultured under organotypic conditions.
AB  - The incidence of esophageal adenocarcinoma (EAC) is rising in the United States.
      An important risk factor for EAC is the presence of Barrett esophagus (BE). BE is
      the replacement of normal squamous esophageal epithelium with a specialized
      columnar epithelium in response to chronic acid and bile reflux. However, the
      emergence of BE from squamous keratinocytes has not yet been demonstrated. Our
      research has focused on this. Wnt and cyclooxygenase 2 (Cox2) are two pathways
      whose activation has been associated with BE and progression to EAC, but their
      role has not been tested experimentally. To explore their contribution, we
      engineered a human esophageal keratinocyte cell line to express either a dominant
      active Wnt effector CatCLef or a Cox2 complementary DNA. In a two-dimensional
      culture environment, Cox2 expression increases cell proliferation and migration,
      but neither transgene induces known BE markers. In contrast, when these cells
      were placed into three-dimensional organotypic culture conditions, we observed
      more profound effects. CatCLef-expressing cells were more proliferative,
      developed a thicker epithelium, and upregulated Notch signaling and several BE
      markers including NHE2. Cox2 expression also increased cell proliferation and
      induced a thicker epithelium. More importantly, we observed cysts form within the
      epithelium, filled with intestinal mucins including Muc5B and Muc17. This
      suggests that Cox2 expression in a three-dimensional culture environment induces
      a lineage of mucin-secreting cells and supports an important causal role for Cox2
      in BE pathogenesis. We conclude that in vitro modeling of BE pathogenesis can be
      improved by enhancing Wnt signaling and Cox2 activity and using three-dimensional
      organotypic culture conditions.

PMID- 21969814
TI  - Activation of pro-uPA is critical for initial escape from the primary tumor and
      hematogenous dissemination of human carcinoma cells.
AB  - Urokinase-type plasminogen activator (uPA) and plasmin have long been implicated
      in cancer progression. However, the precise contributions of the uPA/plasmin
      system to specific steps involved in cancer cell dissemination have not been
      fully established. Herein, we have used a highly disseminating variant of the
      human PC-3 prostate carcinoma cell line, PC-hi/diss, as a prototype of aggressive
      carcinomas to investigate the mechanisms whereby pro-uPA activation and uPA
      generated plasmin functionally contribute to specific stages of metastasis. The
      PC-hi/diss cells secrete and activate significant amounts of pro-uPA, leading to
      efficient generation of plasmin in solution and at the cell surface. In a mouse
      orthotopic xenograft model, treatment with the specific pro-uPA activation
      blocking antibody mAb-112 significantly inhibited local invasion and distant
      metastasis of the PC-hi/diss cells. To mechanistically examine the uPA/plasmin
      mediated aspects of tumor cell dissemination, the anti-pro-uPA mAb-112 and the
      potent serine protease inhibitor, aprotinin, were used in parallel in a number of
      in vivo assays modeling various rate-limiting steps in early metastatic spread.
      Our findings demonstrate that, by generating plasmin, activated tumor-derived uPA
      facilitates early stages of PC-hi/diss dissemination, specifically the escape
      from the primary tumor and tumor cell intravasation. Moreover, through a series
      of in vitro and in vivo analyses, we suggest that PC-hi/diss-invasive escape and
      dissemination may be enhanced by cleavage of stromal fibronectin by uPA-generated
      plasmin. Together, our findings point to inhibition of pro-uPA activation at the
      apex of the uPA/plasmin cascade as a therapy-valid approach to control onset of
      tumor escape and ensuing metastatic spread.

PMID- 21969815
TI  - Human leukocyte antigen E contributes to protect tumor cells from lysis by
      natural killer cells.
AB  - The nonclassic class I human leukocyte antigen E (HLA-E) molecule engages the
      inhibitory NKG2A receptor on several cytotoxic effectors, including natural
      killer (NK) cells. Its tissue distribution was claimed to be wider in normal than
      in neoplastic tissues, and surface HLA-E was undetectable in most tumor cell
      lines. Herein, these issues were reinvestigated taking advantage of HLA-E
      specific antibodies, immunohistochemistry, and biochemical methods detecting
      intracellular and surface HLA-E regardless of conformation. Contrary to published
      evidence, HLA-E was detected in a few normal epithelia and in a large fraction
      (approximately 1/3) of solid tumors, including those derived from HLA-E
      negative/low-normal counterparts. Remarkably, HLA-E was detected in 30 of 30
      tumor cell lines representative of major lymphoid and nonlymphoid lineages, and
      in 11 of 11, it was surface-expressed, although in a conformation poorly reactive
      with commonly used antibodies. Coexpression of HLA-E and HLA class I ligand
      donors was not required for surface expression but was associated with NKG2A
      mediated protection from lysis by the cytotoxic cell line NKL and polyclonal NK
      cells from healthy donors, as demonstrated by antibody-mediated relief of
      protection in 10% to 20% of the tested target-effector combinations. NKG2A
      mediated protection of additional targets became evident on NK effector blocking
      with antibodies to activating receptors (DNAM-1, natural cytotoxicity receptors,
      and NKG2D). Thus, initial evidence that the long-elusive HLA-E molecule is
      enhanced by malignant transformation and is functional in tumor cells is
      presented here, although its importance and precise functional role remain to be
      addressed in the context of a general understanding of the NK ligand-receptor
      network.

PMID- 21969816
TI  - Glioma cell migration on three-dimensional nanofiber scaffolds is regulated by
      substrate topography and abolished by inhibition of STAT3 signaling.
AB  - A hallmark of malignant gliomas is their ability to disperse through neural
      tissue, leading to long-term failure of all known therapies. Identifying new
      antimigratory targets could reduce glioma recurrence and improve therapeutic
      efficacy, but screens based on conventional migration assays are hampered by the
      limited ability of these assays to reproduce native cell motility. Here, we have
      analyzed the motility, gene expression, and sensitivity to migration inhibitors
      of glioma cells cultured on scaffolds formed by submicron-sized fibers
      (nanofibers) mimicking the neural topography. Glioma cells cultured on aligned
      nanofiber scaffolds reproduced the elongated morphology of cells migrating in
      white matter tissue and were highly sensitive to myosin II inhibition but only
      moderately affected by stress fiber disruption. In contrast, the same cells
      displayed a flat morphology and opposite sensitivity to myosin II and actin
      inhibition when cultured on conventional tissue culture polystyrene. Gene
      expression analysis indicated a correlation between migration on aligned
      nanofibers and increased STAT3 signaling, a known driver of glioma progression.
      Accordingly, cell migration out of glioblastoma-derived neurospheres and tumor
      explants was reduced by STAT3 inhibitors at subtoxic concentrations. Remarkably,
      these inhibitors were ineffective when tested at the same concentrations in a
      conventional two-dimensional migration assay. We conclude that migration of
      glioma cells is regulated by topographical cues that affect cell adhesion and
      gene expression. Cell migration analysis using nanofiber scaffolds could be used
      to reproduce native mechanisms of migration and to identify antimigratory
      strategies not disclosed by other in vitro models.

PMID- 21969817
TI  - Hypomethylation of the hsa-miR-191 locus causes high expression of hsa-mir-191
      and promotes the epithelial-to-mesenchymal transition in hepatocellular
      carcinoma.
AB  - hsa-miR-191 is highly expressed in hepatocellular carcinoma (HCC), but the
      factors regulating this elevated expression are unknown. This study aimed to
      investigate the epigenetic mechanisms of increased hsa-miR-191 expression by
      analyzing the relationship between the DNA methylation status of hsa-miR-191 and
      miR-191 expression. Methylation-specific polymerase chain reaction (PCR),
      bisulfite sequencing PCR, Northern blot, and quantitative real-time PCR were
      performed to examine hsa-miR-191 methylation and expression levels. Western blot,
      transwell, and scratch assays were performed to examine the function and
      molecular mechanisms of hsa-miR-191. Approximately 58.9% of hsa-miR-191
      expression was higher in HCC tissues than in adjacent noncancerous tissues; this
      high expression was associated with poor prognosis. The hypomethylation observed
      in some HCC cell lines and HCC tissues was correlated with the hsa-miR-191
      expression level. This correlation was validated by treatment with the 5-aza-DAC
      demethylation agent. The level of hypomethylation was 63.0% in 73 clinical HCC
      tissue samples and was associated with increased (2.1-fold) hsa-miR-191
      expression. The elevated expression of hsa-miR-191 in the SMMC-771 HCC cell line
      induced the cells to transition into mesenchymal-like cells; they exhibited
      characteristics such as loss of adhesion, down-regulation of epithelial cell
      markers, up-regulation of mesenchymal cell markers, and increased cell migration
      and invasion. Inhibiting hsa-miR-191 expression in the SMMC-7721 cell line
      reversed this process (as assessed by cell morphology and cell markers).
      Furthermore, hsa-miR-191 probably exerted its function by directly targeting TIMP
      metallopeptidase inhibitor 3 and inhibiting TIMP3 protein expression. Our results
      suggest that hsa-miR-191 locus hypomethylation causes an increase in hsa-miR-191
      expression in HCC clinical tissues and that this expression induces HCC cells to
      transition into mesenchymal-like cells.

PMID- 21969818
TI  - Inhibition of cyclin-dependent kinase phosphorylation of FOXO1 and prostate
      cancer cell growth by a peptide derived from FOXO1.
AB  - Increasing evidence suggests that FOXO1 possesses a tumor suppressor function.
      Inactivation of FOXO1 has been documented in many types of human cancer, and
      restoring the activity of FOXO1 holds promise for cancer treatment. In this
      study, we identified a FOXO1-derived peptide termed FO1-6nls that inhibits cyclin
      dependent kinases 1 and 2 (CDK1/2)-mediated phosphorylation of FOXO1 at the
      serine 249 residue in vitro and in vivo. Overexpression of FO1-6nls in prostate
      cancer (PCa) cells not only blocked CDK1-induced cytoplasmic localization of
      FOXO1 but also augmented FOXO1's transcriptional activity. This effect of FO1
      6nls requires its binding to CDK1 and CDK2. Moreover, the ectopic expression of
      FO1-6nls inhibited the growth of PTEN-positive DU145 PCa cells. Importantly, the
      growth-inhibitory function of FO1-6nls is dependent on FOXO1. Finally, the
      ectopic expression of FO1-6nls overcame CDK1-mediated inhibition of FOXO1-induced
      apoptosis of PCa cells. These results indicate that the FOXO1-derived peptide FO1
      6nls can restore FOXO1's tumor suppressor function by specifically opposing
      CDK1/2-mediated phosphorylation and inhibition of FOXO1 and hence may have a
      therapeutic potential for the treatment of PCa.

PMID- 21969819
TI  - NRF2 mutation confers malignant potential and resistance to chemoradiation
      therapy in advanced esophageal squamous cancer.
AB  - Esophageal squamous cancer (ESC) is one of the most aggressive tumors of the
      gastrointestinal tract. A combination of chemotherapy and radiation therapy (CRT)
      has improved the clinical outcome, but the molecular background determining the
      effectiveness of therapy remains unknown. NRF2 is a master transcriptional
      regulator of stress adaptation, and gain of-function mutation of NRF2 in cancer
      confers resistance to stressors including anticancer therapy. Direct resequencing
      analysis revealed that Nrf2 gain-of-function mutation occurred recurrently
      (18/82, 22%) in advanced ESC tumors and ESC cell lines (3/10). The presence of
      Nrf2 mutation was associated with tumor recurrence and poor prognosis. Short
      hairpin RNA-mediated down-regulation of NRF2 in ESC cells that harbor only
      mutated Nrf2 allele revealed that themutant NRF2 conferred increased cell
      proliferation, attachment-independent survival, and resistance to 5-fluorouracil
      and gamma-irradiation. Based on the Nrf2 mutation status, gene expression
      signatures associated with NRF2 mutation were extracted from ESC cell lines, and
      their potential utility for monitoring and prognosis was examined in a cohort of
      33 pre-CRT cases of ESC. The molecular signatures of NRF2 mutation were
      significantly predictive and prognostic for CRT response. In conclusion,
      recurrent NRF2 mutation confers malignant potential and resistance to therapy in
      advanced ESC, resulting in a poorer outcome. Molecular signatures of NRF2
      mutation can be applied as predictive markers of response to CRT, and efficient
      inhibition of aberrant NRF2 activation could be a promising approach in
      combination with CRT.

PMID- 21969820
TI  - Lymph node stromal cells enhance drug-resistant colon cancer cell tumor formation
      through SDF-1alpha/CXCR4 paracrine signaling.
AB  - Colorectal cancer (CRC) is the third most common malignancy and the second
      leading cause of cancer-related deaths in America. Nearly two thirds of newly
      diagnosed CRC cases include lymph node (LN) involvement, and LN metastasis is one
      of the strongest negative prognostic factors for CRC. It is thought that CRC
      tumors contain a small population of drug-resistant CRC tumor-initiating cells
      (Co-TICs) that may be responsible for cancer recurrence. To evaluate the effects
      of the LN stromal cells on Co-TICs, we established a unique xenoplant model using
      CRC cells isolated by enzymatic digestion from consented patient specimens, HT-29
      cells, HCA-7 cells, and LN stromal cell line HK cells. We found that HK cells and
      HK cell-conditioned media enhanced CRC tumor formation and tumor angiogenesis.
      Cells expressing CD133(+) and the stromal cell-derived factor 1alpha (SDF-1alpha)
      receptor CXCR4 were enriched in chemotherapeutic-resistant CRC cells.
      CD133(+)CXCR4(+) Co-TICs isolated from patient specimens are more tumorigenic
      than unsorted tumor cells. Furthermore, the inhibitors specific to HK cell
      derived SDF-1alpha reduced tumor formation and tumor angiogenesis. Our results
      have demonstrated a role for Co-TICs in tumor growth and defined the influence of
      LN stromal cells on Co-TICs. We have identified a major Co-TIC/LN
      microenvironment-specific mechanism for CRC resistance to chemotherapeutic agents
      and established experimental platforms for both in vitro and in vivo testing,
      indicating that SDF-1alpha and its receptor, CXCR4, may be targets for clinical
      therapy.

PMID- 21969823
TI  - Capsule retentions and incomplete capsule endoscopy examinations: an analysis of
      2300 examinations.
AB  - Aim. To evaluate capsule endoscopy in terms of incomplete examinations and
      capsule retentions and to find risk factors for these events. Material and
      Methods. This retrospective and consecutive study includes data from 2300 capsule
      enteroscopy examinations, performed at four different hospitals in Stockholm,
      Sweden from 2003 to 2009. Results. The frequency of incomplete examinations was
      20%. Older age, male gender, suspected, and known Crohn's disease were risk
      factors for an incomplete examination. The PillCam capsule had the highest rate
      of completed examinations. Capsule retention occurred in 1.3% (n = 31). Risk
      factors for capsule retention were known Crohn's disease and suspected tumor.
      Complications of capsule retention were acute obstructive symptoms in six
      patients and one death related to complications after acute surgical capsule
      retrieval. CONCLUSION: Capsule endoscopy is considered a safe procedure, although
      obstructive symptoms and serious complications due to capsule retention can be
      found in a large series of patients.

PMID- 21969822
TI  - Maternal obesity and developmental programming of metabolic disorders in
      offspring: evidence from animal models.
AB  - The incidence of obesity and overweight has reached epidemic proportions in the
      developed world as well as in those countries transitioning to first world
      economies, and this represents a major global health problem. Concern is rising
      over the rapid increases in childhood obesity and metabolic disease that will
      translate into later adult obesity. Although an obesogenic nutritional
      environment and increasingly sedentary lifestyle contribute to our risk of
      developing obesity, a growing body of evidence links early life nutritional
      adversity to the development of long-term metabolic disorders. In particular, the
      increasing prevalence of maternal obesity and excess maternal weight gain has
      been associated with a heightened risk of obesity development in offspring in
      addition to an increased risk of pregnancy-related complications. The mechanisms
      that link maternal obesity to obesity in offspring and the level of gene
      environment interactions are not well understood, but the early life environment
      may represent a critical window for which intervention strategies could be
      developed to curb the current obesity epidemic. This paper will discuss the
      various animal models of maternal overnutrition and their importance in our
      understanding of the mechanisms underlying altered obesity risk in offspring.

PMID- 21969825
TI  - A new look at trigger point injections.
AB  - Trigger point injections are commonly practised pain interventional techniques.
      However, there is still lack of objective diagnostic criteria for trigger points.
      The mechanisms of action of trigger point injection remain obscure and its
      efficacy remains heterogeneous. The advent of ultrasound technology in the
      noninvasive real-time imaging of soft tissues sheds new light on visualization of
      trigger points, explaining the effect of trigger point injection by blockade of
      peripheral nerves, and minimizing the complications of blind injection.

PMID- 21969824
TI  - Lipid emulsion for local anesthetic systemic toxicity.
AB  - The accidental overdose of local anesthetics may prove fatal. The commonly used
      amide local anesthetics have varying adverse effects on the myocardium, and
      beyond a certain dose all are capable of causing death. Local anesthetics are the
      most frequently used drugs amongst anesthetists and although uncommon, local
      anaesthetic systemic toxicity accounts for a high proportion of mortality, with
      local anaesthetic-induced cardiac arrest particularly resistant to standard
      resuscitation methods. Over the last decade, there has been convincing evidence
      of intravenous lipid emulsions as a rescue in local anesthetic-cardiotoxicity,
      and anesthetic organisations, over the globe have developed guidelines on the use
      of this drug. Despite this, awareness amongst practitioners appears to be
      lacking. All who use local anesthetics in their practice should have an
      appreciation of patients at high risk of toxicity, early symptoms and signs of
      toxicity, preventative measures when using local anesthetics, and the initial
      management of systemic toxicity with intravenous lipid emulsion. In this paper we
      intend to discuss the pharmacology and pathophysiology of local anesthetics and
      toxicity, and the rationale for lipid emulsion therapy.

PMID- 21969826
TI  - An anticipatory geriatric strategy: to better care for those americans not yet
      old.
AB  - Current US public policy decisions will have impact on national plans to care for
      the aging American baby boomer population over the next several decades. The
      recent health care legislative debate has been largely about the structure of
      health care for those still too young to be covered by Medicare, but the
      legislation may have important implications for the average rates of accumulating
      chronic illness and disability in midlife and influence the care needs for that
      cohort of individuals even after they become elderly.

PMID- 21969827
TI  - Living alone, loneliness, and psychological well-being of older persons in
      singapore.
AB  - Studies of the psychological well-being of elderly living alone have yielded
      inconsistent results. Few investigators have distinguished living alone from
      loneliness in the same study. Thus, the present study examined the independent
      and interactive effects of living alone and loneliness on depressive symptoms
      (GDS score) and quality of life (SF-12 MCS score) in a prospective 2-year follow
      up cohort study of 2808 community-dwelling older adults (aged >=55 years) in
      Singapore, controlling for baseline covariates. In cross-sectional analysis,
      loneliness was a more robust predictor of GDS score than living arrangements;
      living alone, when controlled for loneliness, was not associated with GDS score.
      GDS score associated with living alone was worse for those who felt lonely than
      for those who did not feel lonely. Similar patterns of association were found in
      longitudinal analyses and for SF-12 MCS score, although not all were significant.
      Thus, though living alone predicted lower psychological well-being, its
      predictive ability was reduced when loneliness was taken into account and
      loneliness, a stronger predictor, worsened the psychological effects of living
      alone.

PMID- 21969828
TI  - Well-differentiated thyroid carcinomas: management of the central lymph node
      compartment and emerging biochemical markers.
AB  - Well-differentiated thyroid cancers (WDTCs) are generally indolent cancers that
      are associated with a low mortality. Although the incidence of these tumors is
      increasing, there has not been an associated increase in the mortality rates. As
      we gain a greater understanding and more experience with these good prognosis
      cancers, the way in which we treat these tumors is evolving. The definition of
      persistent or recurrent disease has seen a shift from being a clinical and/or
      radiological diagnosis to now one based on a biochemical blood marker,
      thyroglobulin. Central lymph node metastases are a very common problem in WDTC,
      being present in up to 90% of patients. The optimal surgical management of the
      central lymph node compartment remains a hotly debated topic. This paper
      identifies these controversies and presents available data surrounding these
      issues. Biochemical tumor markers are gaining wider use in practice and in time
      hopefully provide more specific information with which surgical decision-making
      can be based. A summary of the clinically available markers is presented.

PMID- 21969830
TI  - The blood compatibilities of blood purification membranes and other materials
      developed in Japan.
AB  - The biocompatibilities in blood purification therapy are defined as "a concept to
      stipulate safety of blood purification therapy by an index based on interaction
      in the body arising from blood purification therapy itself." The
      biocompatibilities are associated with not only materials to be used but also
      many factors such as sterilization method and eluted substance. It is often
      evaluated based on impacts on cellular pathways and on humoral pathways. Since
      the biocompatibilities of blood purification therapy in particular hemodialysis
      are not just a prognostic factor for dialysis patients but a contributory factor
      for long-term complications, it should be considered with adequate attention. It
      is important that blood purification therapy should be performed by consistently
      evaluating not only risks associated with these biocompatibilities but also the
      other advantages obtained from treatments. In this paper, the biocompatibilities
      of membrane and adsorption material based on Japanese original which are used for
      blood purification therapy are described.

PMID- 21969829
TI  - The Amazing Power of Cancer Cells to Recapitulate Extraembryonic Functions: The
      Cuckoo's Tricks.
AB  - Inflammation is implicated in tumor development, invasion, and metastasis. Hence,
      it has been suggested that common cellular and molecular mechanisms are activated
      in wound repair and in cancer development. In addition, it has been previously
      proposed that the inflammatory response, which is associated with the wound
      healing process, could recapitulate ontogeny through the reexpression of the
      extraembryonic, that is, amniotic and vitelline, functions in the interstitial
      space of the injured tissue. If so, the use of inflammation by the cancer
      initiating cell can also be supported in the ability to reacquire extraembryonic
      functional axes for tumor development, invasion, and metastasis. Thus, the
      diverse components of the tumor microenvironment could represent the overlapping
      reexpression of amniotic and vitelline functions. These functions would favor a
      gastrulation-like process, that is, the creation of a reactive stroma in which
      fibrogenesis and angiogenesis stand out.

PMID- 21969831
TI  - Contribution of primary pelvic organ prolapse to micturition and defecation
      symptoms.
AB  - Objective. To investigate the contribution of Pelvic Organ Prolapse (POP) to
      micturition and defecation symptoms. Method. Cross-sectional study including 64
      women presenting with POP symptoms and 50 controls without POP complaints.
      Subjects were evaluated using POP-Quantification system, Urinary Distress
      Inventory, and Defecation Distress Inventory. The MOS SF-36 health survey and the
      Center for Epidemiological Studies Depression scale were used to measure self
      perceived health status and depressive symptoms, respectively. Results. POP in
      terms of POP-Q had a moderate impact on the symptom observing vaginal protrusion
      (explained variance 0.31). It contributed modestly to obstructive voiding and
      overactive bladder symptoms (explained variance 0.09, resp., 0.14) but not to
      urinary incontinence. Constipation was more likely explained by clinical
      depression than by pelvic floor defects (explained variance 0.13, resp., 0.05).
      Conclusion. Stage of POP and specific prolapse symptoms are associated but such a
      strong association does not exist between POP and micturition or defecation
      symptoms.

PMID- 21969832
TI  - Very late relapse of testicular tumour in combination with renal cancer and their
      retroperitoneoscopic removal.
AB  - Late relapse of a testicular cancer is an uncommon occurrence. We report a case
      of late relapse of a testicular tumour combined with a renal cancer and their
      successful removal with retroperitoneoscopy. The 36-year-old patient underwent
      left orchiectomy, retroperitoneal lymph node dissection, and chemotherapy,
      because of mixed tumor including teratoma and embryonal carcinoma. 18 years after
      the successful primary therapy elevated serum alpha-fetoprotein level had been
      confirmed, then MRI and PET-CT scans demonstrated a 30 mm left renal mass and 22
      mm retroperitoneal lymph node above the bifurcation of the left common iliac
      artery. We performed retroperitoneoscopic lymph node dissection and left renal
      tumour resection in the same session. The histology revealed embryonal carcinoma
      for the retroperitoneal lymph node and renal cell carcinoma for the left renal
      mass. We can conclude that late followup of patients with testicular tumour is
      important. Retroperitoneoscopy is feasible approach for the removal of
      retroperitoneal lymph node metastasis and resection of renal tumor.

PMID- 21969833
TI  - Rectovesical fistula related to transurethral resection of a bladder lesion.
AB  - A rectovesical fistula (RVF) is an uncommon complication of urooncologic surgery.
      Although several RVFs have been reported, our case is the first reported RVF in
      the literature that iatrogenically occurred after transurethral resection of the
      bladder. A single-stage primary repair with omental flap interposition without a
      colostomy was successfully performed because of the persistence of the fistula
      during followup. After 6 months of followup, no fistula or bladder mass was
      detected.

PMID- 21969834
TI  - Endobronchial lipoma: an unusual cause of bronchial obstruction.
AB  - Endobronchial lipoma is a rare benign tumor. It is difficult to differentiate
      benign endobronchial lipoma from their malignant counterparts, as their symptoms
      and complications are almost alike. Here, we describe the clinical and
      radiological features of EL in two cases. Multislice CT (MSCT) may play an
      important role in the diagnosis for EL.

PMID- 21969835
TI  - Nuclear reprogramming in mouse primordial germ cells: epigenetic contribution.
AB  - The unique capability of germ cells to give rise to a new organism, allowing the
      transmission of primary genetic information from generation to generation,
      depends on their epigenetic reprogramming ability and underlying genomic
      totipotency. Recent studies have shown that genome-wide epigenetic modifications,
      referred to as "epigenetic reprogramming", occur during the development of the
      gamete precursors termed primordial germ cells (PGCs) in the embryo. This
      reprogramming is likely to be critical for the germ line development itself and
      necessary to erase the parental imprinting and setting the base for totipotency
      intrinsic to this cell lineage. The status of genome acquired during
      reprogramming and the associated expression of key pluripotency genes render PGCs
      susceptible to transform into pluripotent stem cells. This may occur in vivo
      under still undefined condition, and it is likely at the origin of the formation
      of germ cell tumors. The phenomenon appears to be reproduced under partly defined
      in vitro culture conditions, when PGCs are transformed into embryonic germ (EG)
      cells. In the present paper, I will try to summarize the contribution that
      epigenetic modifications give to nuclear reprogramming in mouse PGCs.

PMID- 21969836
TI  - Understanding household behavioral risk factors for diarrheal disease in Dar es
      Salaam: a photovoice community assessment.
AB  - Whereas Tanzania has seen considerable improvements in water and sanitation
      infrastructure over the past 20 years, the country still faces high rates of
      childhood morbidity from diarrheal diseases. This study utilized a qualitative,
      cross-sectional, modified Photovoice method to capture daily activities of Dar es
      Salaam mothers. A total of 127 photographs from 13 households were examined, and
      13 interviews were conducted with household mothers. The photographs and
      interviews revealed insufficient hand washing procedures, unsafe disposal of
      wastewater, uncovered household drinking water containers, a lack of water
      treatment prior to consumption, and inappropriate toilets for use by small
      children. The interviews revealed that mothers were aware and knowledgeable of
      the risks of certain household practices and understood safer alternatives, yet
      were restricted by the perceived impracticality and financial constraints to make
      changes. The results draw attention to the real economic and behavioral
      challenges faced in reducing the spread of disease.

PMID- 21969837
TI  - Dendritic cell-based vaccines positively impact natural killer and regulatory T
      cells in hepatocellular carcinoma patients.
AB  - Immunotherapy of cancer must promote antitumor effector cells for tumor
      eradication as well as counteract immunoregulatory mechanisms which inhibit
      effectors. Immunologic therapies of cancer are showing promise, including
      dendritic cell-(DC-) based strategies. DC are highly malleable antigen-presenting
      cells which can promote potent antitumor immunity as well as tolerance, depending
      on the environmental signals received. Previously, we tested a peptide-pulsed DC
      vaccine to promote Alpha-fetoprotein (AFP-) specific anti-tumor immunity in
      patients with hepatocellular carcinoma (HCC), and reported on the CD8+ T cell
      responses induced by this vaccine and the clinical trial results. Here, we show
      that the peptide-loaded DC enhanced NK cell activation and decreased regulatory T
      cells (Treg) frequencies in vaccinated HCC patients. We also extend these data by
      testing several forms of DC vaccines in vitro to determine the impact of antigen
      loading and maturation signals on both NK cells and Treg from healthy donors and
      HCC patients.

PMID- 21969839
TI  - Adaptive immunity in ankylosing spondylitis: phenotype and functional alterations
      of T-cells before and during infliximab therapy.
AB  - Our aim was to assess the phenotype of T-cell subsets in patients with ankylosing
      spondylitis (AS), a chronic inflammatory rheumatic disease. In addition, we also
      tested short-term T-cell activation characteristics. Measurements were done in 13
      AS patients before and during the intravenous therapy with anti-TNF agent
      infliximab (IFX). Flow cytometry was used to determine T-cell subsets in
      peripheral blood and their intracellular signaling during activation. The
      prevalence of Th2 and Th17 cells responsible for the regulation of adaptive
      immunity was higher in AS than in 9 healthy controls. Although IFX therapy
      improved patients' condition, immune phenotype did not normalize. Cytoplasmic and
      mitochondrial calcium responses of CD4+ and CD8+ cells to a specific activation
      were delayed, while NO generation was increased in AS. NO generation normalized
      sooner upon IFX than calcium response. These results suggest an abnormal immune
      phenotype with functional disturbances of CD4+ and CD8+ cells in AS.

PMID- 21969838
TI  - Evaluation of Epstein-Barr virus latent membrane protein 2 specific T-cell
      receptors driven by T-cell specific promoters using lentiviral vector.
AB  - Transduction of latent membrane protein 2 (LMP2)-specific T-cell receptors into
      activated T lymphocytes may provide a universal, MHC-restricted mean to treat EBV
      associated tumors in adoptive immunotherapy. We compared TCR-specific promoters
      of distinct origin in lentiviral vectors, that is, Vbeta6.7, delta, luria, and
      Vbeta5.1 to evaluate TCR gene expression in human primary peripheral blood
      monocytes and T cell line HSB2. Vectors containing Vbeta 6.7 promoter were found
      to be optimal for expression in PBMCs, and they maintained expression of the
      transduced TCRs for up to 7 weeks. These cells had the potential to recognize
      subdominant EBV latency antigens as measured by cytotoxicity and IFN-gamma
      secretion. The nude mice also exhibited significant resistance to the HLA-A2 and
      LMP2-positive CNE tumor cell challenge after being infused with lentiviral
      transduced CTLs. In conclusion, LMP2-specific CTLs by lentiviral transduction
      have the potential use for treatment of EBV-related tumors.

PMID- 21969840
TI  - Current concepts of immunology and diagnosis in amniotic fluid embolism.
AB  - Amniotic fluid embolism (AFE) is one of the leading causes of maternal mortality
      and morbidity in developed countries. Current thinking about pathophysiology has
      shifted away from embolism toward a maternal immune response to the fetus. Two
      immunologic mechanisms have been studied to date. Anaphylaxis appears to be
      doubtful while the available evidence supports a role for complement activation.
      With the mechanism remaining to be elucidated, AFE remains a clinical diagnosis.
      It is diagnosed based on one or more of four key signs/symptoms: cardiovascular
      collapse, respiratory distress, coagulopathy, and/or coma/seizures. The only
      laboratory test that reliably supports the diagnosis is the finding of fetal
      material in the maternal pulmonary circulation at autopsy. Perhaps the most
      compelling mystery surrounding AFE is not why one in 20,000 parturients are
      afflicted, but rather how the vast majority of women can tolerate the foreign
      antigenic presence of their fetus both within their uterus and circulation?

PMID- 21969841
TI  - Molecular Characterization and Expression of alpha-Globin and beta-Globin Genes
      in the Euryhaline Flounder (Platichthys flesus).
AB  - In order to understand the possible role of globin genes in fish salinity
      adaptation, we report the molecular characterization and expression of all four
      subunits of haemoglobin, and their response to salinity challenge in flounder.
      The entire open reading frames of alpha1-globin and alpha2-globin genes were 432
      and 435 bp long, respectively, whereas the beta1-globin and beta2-globin genes
      were both 447 bp. Although the head kidney (pronephros) is the predicted major
      site of haematopoiesis, real-time PCR revealed that expression of alpha-globin
      and beta-globin in kidney (mesonephros) was 1.5 times higher than in head kidney.
      Notably, the alpha1-globin and beta1-globin mRNA expression was higher than
      alpha2-globin and beta2-globin in kidney. Expression levels of all four globin
      subunits were higher in freshwater- (FW-) than in seawater- (SW-)adapted fish
      kidney. If globins do play a role in salinity adaptation, this is likely to be
      more important in combating the hemodilution faced by fish in FW than the
      dehydration and salt loading which occur in SW.

PMID- 21969842
TI  - Levels of tannins and flavonoids in medicinal plants: evaluating bioprospecting
      strategies.
AB  - There are several species of plants used by traditional communities in the
      Brazilian semiarid. An approach used in the search for natural substances that
      possess therapeutic value is ethnobotany or ethnopharmacology. Active substances
      that have phenolic groups in their structure have great pharmacological
      potential. To establish a quantitative relationship between the species popularly
      considered to be antimicrobial, antidiabetic, and antidiarrheal, the contents of
      tannins and flavonoids were determined. The plant selection was based on an
      ethnobotanical survey conducted in a community located in the municipality of
      Altinho, northeastern Brazil. For determination of tannin content was utilized
      the technique of radial diffusion, and for flavonoids, an assay based on the
      complexation of aluminum chloride. The group of plants with antimicrobial
      indications showed a higher content of tannins compared to the control groups.
      The results evidence suggests a possible relationship between these compounds and
      the observed activity.

PMID- 21969843
TI  - The first report on the medicinal use of fossils in latin america.
AB  - There have been very few ethnopharmacological studies performed on the
      traditional use of fossil species, although a few records have been conducted in
      Asia, Africa, and Europe. This study is the first ever to be performed on the use
      of Testudine (turtle) fossils for folk medicine in Latin America. An
      investigation was conducted in the Araripe Basin, which is one of the most
      important fossil-bearing reserves in the world due to the diversity, endemism,
      and quality of preservation of its fossils. We propose the formalization of a new
      discipline called ethnopaleontology, which will involve the study of the dynamic
      relationship between humans and fossils, from human perception to direct use.

PMID- 21969844
TI  - Unusual cases of hydronephrosis with retroperitoneal fibrosis: mystery revealed.

PMID- 21969845
TI  - High cut-off haemodialysis induces remission of recurrent idiopathic focal
      segmental glomerulosclerosis after renal transplantation but is no alternative to
      plasmapheresis.
AB  - A 26-year-old male experienced a recurrence of idiopathic focal segmental
      glomerulosclerosis (iFSGS) after his second renal transplant. Reduction of
      proteinuria was rapidly induced by plasmapheresis (PP) and the patient has
      remained in remission with a once-weekly PP regimen, which has now been continued
      for >31/2 years. We were also able to induce remission of iFSGS in this patient
      by treatment with high cut-off haemodialysis using the TheraliteTM dialyser. This
      observation lends support for the pathophysiological role of an as yet unknown,
      circulating glomerular filtration barrier permeability factor with an estimated
      weight of between 30 and 50 kDa.

PMID- 21969846
TI  - Management of residual mass in nonseminomatous germ cell tumors following
      chemotherapy.
AB  - Advanced stage nonseminomatous testis cancer is commonly treated with
      chemotherapy and surgical resection. Patients with retroperitoneal residual
      masses >1cm following induction chemotherapy with normalized tumor markers should
      undergo a post-chemotherapy retroperitoneal lymph node dissection. Post
      chemotherapy retroperitoneal residual mass less than 1 cm with normal markers may
      be considered as complete response, although the possibility of residual teratoma
      and viable germ cell tumor are not definitively ruled out. Excellent long term
      disease free survival following surveillance may justify this option as the
      treatment of choice in this cohort of patients.

PMID- 21969848
TI  - Focal therapy for prostate cancer - where are we in 2011?
AB  - Prostate cancer treatment is a controversial topic amongst physicians and
      patients alike. Radical therapies such as prostatectomy and whole gland radiation
      offer the best outcomes in terms of oncologic efficacy, but the decision to
      undergo treatment must be weighed against its potential morbidity. Over the past
      decade, the concept of focal therapy for prostate cancer has been introduced as a
      potential method of achieving oncologic control with a lesser degree of
      morbidity. Focal therapy refers to isolated ablation of a tumor focus with
      sparing of uninvolved, surrounding tissue. While it remains in the early stages
      of development, considerable research is underway that will help determine the
      optimal method of achieving this goal. Current areas of investigation include
      appropriate candidate selection, lesion identification, modality of treatment,
      and follow-up strategies.

PMID- 21969847
TI  - Surgery for high-risk localized prostate cancer.
AB  - Treatment of men with high-risk prostate cancer (PCa) remains challenging for
      urologists. The complex natural history of high-risk PCa and the lack of specific
      and accurate definitions for high-risk disease impede treatment decision making.
      Historically, surgery in this patient group has been avoided based on the
      perception of ostensibly higher complication rates associated with inferior
      functional and oncological outcomes. To date, no randomized data comparing
      different therapy approaches have been made available. Several investigators have
      reported that continence rates in patients after radical prostatectomy (RP) for
      high-risk disease seem to be unaffected. Similarly, in a large proportion of
      these men, a nerve-sparing procedure can be performed without a significant
      negative impact on surgical margin rates and with comparable potency results.
      Moreover, extended pelvic lymph node dissection (EPLND) contributes to accurate
      pathological staging with a marginal effect on perioperative morbidity. With
      regards to the benefits of RP on local recurrence and cure rates, realistic
      expectations regarding the success of RP alone or in the context of a multimodal
      approach should be provided during patient counseling.

PMID- 21969849
TI  - Serenoa repens extract in the treatment of benign prostatic hyperplasia.
AB  - We are experiencing a revival of interest in phytotherapeutic agents, both in
      Europe and North America, especially as a consequence of patients'
      dissatisfaction with the adverse effects of the medical alternatives. One of the
      most frequently prescribed and studied such agents is Serenoa repens extract,
      derived from the berry of the dwarf palm tree. We aimed to review the most
      important published data regarding this type of treatment for benign prostatic
      hyperplasia. A review of the existing articles regarding the use of Serenoa
      repens extracts for benign prostatic hyperplasia was performed. The articles were
      analysed with regard to their relevance, scientific value and the size of the
      evaluated series. Multiple mechanisms of action have been attributed to this
      extract, including antiandrogenic action, an anti-inflammatory/anti-oedematous
      effect, prolactin signal modulation, and an antiproliferative effect exerted
      through the inhibition of growth factors. Regarding efficacy, European
      Association of Urology guidelines state that Serenoa repens extracts
      significantly reduce nocturia in comparison with placebo. However, the guideline
      committee is unable to make specific recommendations about phytotherapy of male
      lower urinary tract symptoms owing to the heterogeneity of the products and the
      methodological problems associated with meta-analyses. Most of the published
      trials regarding Serenoa repens phytotherapy demonstrate a significant
      improvement of urinary status and a favourable safety profile. Also, some authors
      have credited it with giving a significant improvement in erectile function and
      decreasing complications following transurethral resection of the prostate,
      especially bleeding. The results of phytotherapy with Serenoa repens extracts are
      very promising. More high-quality, randomized, placebo-controlled studies are
      required in order to demonstrate without doubt the true therapeutic value of
      these products. Particular attention must be focused on differentiating between
      registered preparations, which are regulated as drugs, and those considered to be
      food supplements.

PMID- 21969850
TI  - Spinal astrocytic activation is involved in a virally-induced rat model of
      neuropathic pain.
AB  - Postherpetic neuralgia (PHN), the most common complication of herpes zoster (HZ),
      plays a major role in decreased life quality of HZ patients. However, the neural
      mechanisms underlying PHN remain unclear. Here, using a PHN rat model at 2 weeks
      after varicella zoster virus infection, we found that spinal astrocytes were
      dramatically activated. The mechanical allodynia and spinal central sensitization
      were significantly attenuated by intrathecally injected L-alpha-aminoadipate
      (astrocytic specific inhibitor) whereas minocycline (microglial specific
      inhibitor) had no effect, which indicated that spinal astrocyte but not microglia
      contributed to the chronic pain in PHN rat. Further study was taken to
      investigate the molecular mechanism of astrocyte-incudced allodynia in PHN rat at
      post-infection 2 weeks. Results showed that nitric oxide (NO) produced by
      inducible nitric oxide synthase mediated the development of spinal astrocytic
      activation, and activated astrocytes dramatically increased interleukin-1beta
      expression which induced N-methyl-D-aspartic acid receptor (NMDAR)
      phosphorylation in spinal dorsal horn neurons to strengthen pain transmission.
      Taken together, these results suggest that spinal activated astrocytes may be one
      of the most important factors in the pathophysiology of PHN and "NO-Astrocyte
      Cytokine-NMDAR-Neuron" pathway may be the detailed neural mechanisms underlying
      PHN. Thus, inhibiting spinal astrocytic activation may represent a novel
      therapeutic strategy for clinical management of PHN.

PMID- 21969852
TI  - Effects of visual priming on taste-odor interaction.
AB  - Little is known about the influence of visual characteristics other than colour
      on flavor perception, and the complex interactions between more than two sensory
      modalities. This study focused on the effects of recognizability of visual
      (texture) information on flavor perception of odorized sweet beverages.
      Participants rated the perceived sweetness of odorized sucrose solutions in the
      presence or absence of either a congruent or incongruent visual context. Odors
      were qualitatively reminiscent of sweet foods (strawberry and caramel) or not
      (savoury). Visual context was either an image of the same sweet foods (figurative
      context) or a visual texture derived from this product (non-figurative context).
      Textures were created using a texture synthesis method that preserved perceived
      food qualities while removing object information. Odor-taste combinations were
      rated sweeter within a figurative than a non-figurative context. This behaviour
      was exhibited for all odor-taste combinations, even in trials without images,
      indicating sustained priming by figurative visual context. A non-figurative
      context showed a transient sweetening effect. Sweetness was generally enhanced
      most by the strawberry odor. We conclude that the degree of recognizability of
      visual information (figurative versus non-figurative), influences flavor
      perception differently. Our results suggest that this visual context priming is
      mediated by separate sustained and transient processes that are differently
      evoked by figurative and non-figurative visual contexts. These components operate
      independent of the congruency of the image-odor-taste combinations.

PMID- 21969853
TI  - Estimating the under-five mortality rate using a bayesian hierarchical time
      series model.
AB  - BACKGROUND: Millennium Development Goal 4 calls for a reduction in the under-five
      mortality rate by two-thirds between 1990 and 2015, which corresponds to an
      annual rate of decline of 4.4%. The United Nations Inter-Agency Group for Child
      Mortality Estimation estimates under-five mortality in every country to measure
      progress. For the majority of countries, the estimates within a country are based
      on the assumption of a piece-wise constant rate of decline. METHODS AND FINDINGS:
      This paper proposes an alternative method to estimate under-five mortality, such
      that the underlying rate of change is allowed to vary smoothly over time using a
      time series model. Information about the average rate of decline and changes
      therein is exchanged between countries using a bayesian hierarchical model. Cross
      validation exercises suggest that the proposed model provides credible bounds for
      the under-five mortality rate that are reasonably well calibrated during the
      observation period. The alternative estimates suggest smoother trends in under
      five mortality and give new insights into changes in the rate of decline within
      countries. CONCLUSIONS: The proposed model offers an alternative modeling
      approach for obtaining estimates of under-five mortality which removes the
      restriction of a piece-wise linear rate of decline and introduces hierarchy to
      exchange information between countries. The newly proposed estimates of the rate
      of decline in under-5 mortality and the uncertainty assessments would help to
      monitor progress towards Millennium Development Goal 4.

PMID- 21969851
TI  - First phase 1 double-blind, placebo-controlled, randomized rectal microbicide
      trial using UC781 gel with a novel index of ex vivo efficacy.
AB  - OBJECTIVES: Successful control of the HIV/AIDS pandemic requires reduction of HIV
      1 transmission at sexually-exposed mucosae. No prevention studies of the higher
      risk rectal compartment exist. We report the first-in-field Phase 1 trial of a
      rectally-applied, vaginally-formulated microbicide gel with the RT-inhibitor
      UC781 measuring clinical and mucosal safety, acceptability and plasma drug
      levels. A first-in-Phase 1 assessment of preliminary pharmacodynamics was
      included by measuring changes in ex vivo HIV-1 suppression in rectal biopsy
      tissue after exposure to product in vivo. METHODS: HIV-1 seronegative, sexually
      abstinent men and women (N = 36) were randomized in a double-blind, placebo
      controlled trial comparing UC781 gel at two concentrations (0.1%, 0.25%) with
      placebo gel (1?1?1). Baseline, single-dose exposure and a separate, 7-day at-home
      dosing were assessed. Safety and acceptability were primary endpoints. Changes in
      colorectal mucosal markers and UC781 plasma drug levels were secondary endpoints;
      ex vivo biopsy infectibility was an ancillary endpoint. RESULTS: All 36 subjects
      enrolled completed the 7-14 week trial (100% retention) including 3 flexible
      sigmoidoscopies, each with 28 biopsies (14 at 10 cm; 14 at 30 cm). There were 81
      Grade 1 adverse events (AEs) and 8 Grade 2; no Grade 3, 4 or procedure-related
      AEs were reported. Acceptability was high, including likelihood of future use. No
      changes in mucosal immunoinflammatory markers were identified. Plasma levels of
      UC781 were not detected. Ex vivo infection of biopsies using two titers of HIV
      1(BaL) showed marked suppression of p24 in tissues exposed in vivo to 0.25%
      UC781; strong trends of suppression were seen with the lower 0.1% UC781
      concentration. CONCLUSIONS: Single and 7-day topical rectal exposure to both
      concentrations of UC781 were safe with no significant AEs, high acceptability, no
      detected plasma drug levels and no significant mucosal changes. Ex vivo biopsy
      infections demonstrated marked suppression of HIV infectibility, identifying a
      potential early biomarker of efficacy. (Registered at ClinicalTrials.gov;
      #NCT00408538).

PMID- 21969854
TI  - Positive Darwinian selection in the piston that powers proton pumps in complex I
      of the mitochondria of Pacific salmon.
AB  - The mechanism of oxidative phosphorylation is well understood, but evolution of
      the proteins involved is not. We combined phylogenetic, genomic, and structural
      biology analyses to examine the evolution of twelve mitochondrial encoded
      proteins of closely related, yet phenotypically diverse, Pacific salmon. Two
      separate analyses identified the same seven positively selected sites in ND5. A
      strong signal was also detected at three sites of ND2. An energetic coupling
      analysis revealed several structures in the ND5 protein that may have co-evolved
      with the selected sites. These data implicate Complex I, specifically the piston
      arm of ND5 where it connects the proton pumps, as important in the evolution of
      Pacific salmon. Lastly, the lineage to Chinook experienced rapid evolution at the
      piston arm.

PMID- 21969855
TI  - Origin and epidemiological history of HIV-1 CRF14_BG.
AB  - BACKGROUND: CRF14_BG isolates, originally found in Spain, are characterized by
      CXCR4 tropism and rapid disease progression. This study aimed to identify the
      origin of CRF14_BG and reconstruct its epidemiological history based on new
      isolates from Portugal. METHODOLOGY/PRINCIPAL FINDINGS: C2V3C3 env gene sequences
      were obtained from 62 samples collected in 1993-1998 from Portuguese HIV-1
      patients. Full-length genomic sequences were obtained from three patients. Viral
      subtypes, diversity, divergence rate and positive selection were investigated by
      phylogenetic analysis. The molecular structure of the genomes was determined by
      bootscanning. A relaxed molecular clock model was used to date the origin of
      CRF14_BG. Geno2pheno was used to predict viral tropism. Subtype B was the most
      prevalent subtype (45 sequences; 73%) followed by CRF14_BG (8; 13%), G (4; 6%),
      F1 (2; 3%), C (2; 3%) and CRF02_AG (1; 2%). Three CRF14_BG sequences were derived
      from 1993 samples. Near full-length genomic sequences were strongly related to
      the CRF14_BG isolates from Spain. Genetic diversity of the Portuguese isolates
      was significantly higher than the Spanish isolates (0.044 vs 0.014, P<0.0001).
      The mean date of origin of the CRF14_BG cluster was estimated to be 1992 (range,
      1989 and 1996) based on the subtype G genomic region and 1989 (range, 1984-1993)
      based on the subtype B genomic region. Most CRF14_BG strains (78.9%) were
      predicted to be CXCR4. Finally, up to five amino acids were under selective
      pressure in subtype B V3 loop whereas only one was found in the CRF14_BG cluster.
      CONCLUSIONS: CRF14_BG emerged in Portugal in the early 1990 s soon after the
      beginning of the HIV-1 epidemics, spread to Spain in late 1990 s as a consequence
      of IVDUs migration and then to the rest of Europe. CXCR4 tropism is a general
      characteristic of this CRF that may have been selected for by escape from
      neutralizing antibody response.

PMID- 21969856
TI  - Inferring network connectivity by delayed feedback control.
AB  - We suggest a control based approach to topology estimation of networks with N
      elements. This method first drives the network to steady states by a delayed
      feedback control; then performs structural perturbations for shifting the steady
      states M times; and finally infers the connection topology from the steady
      states' shifts by matrix inverse algorithm (M = N) or l(1)-norm convex
      optimization strategy applicable to estimate the topology of sparse networks from
      M << N perturbations. We discuss as well some aspects important for applications,
      such as the topology reconstruction quality and error sources, advantages and
      disadvantages of the suggested method, and the influence of (control)
      perturbations, inhomegenity, sparsity, coupling functions, and measurement noise.
      Some examples of networks with Chua's oscillators are presented to illustrate the
      reliability of the suggested technique.

PMID- 21969857
TI  - A ubiquitin independent degradation pathway utilized by a hepatitis B virus
      envelope protein to limit antigen presentation.
AB  - Hepatitis B virus envelope glycoproteins Large (L), Middle (M) and Small (S) are
      targets of the host cellular immune system. The extent to which the host
      recognizes viral antigens presented by infected cells is believed to play a
      decisive role in determining if an infection will be resolved or become chronic.
      As with other antigens, HBV envelope polypeptides must be degraded, presumably by
      cellular proteasomes, to be presented by the MHC I pathway. We have used M as a
      model to study this process and determine how ER quality control monitors these
      foreign polymeric proteins and disposes of them through the ER-associated
      degradation (ERAD) pathway. Using both wild type and mutant HBV M protein, we
      found that unlike most ERAD substrates, which require ubiquitination for
      retrotranslocation and degradation, the HBV M protein, which only contains two
      lysine residues, can undergo rapid and complete, ubiquitin independent,
      proteasome dependent degradation. The utilization of this pathway had a
      functional consequence, since proteins degraded through it, were poorly presented
      via MHC I. To test the hypothesis that the level of ubiquitination, independent
      of protein degradation, controls the level of antigen presentation, we inserted
      two additional lysines into both the wild type and mutant M protein. Amazingly,
      while the addition of the lysine residues dramatically increased the level of
      ubiquitination, it did not alter the rate of degradation. However and remarkably,
      the increased ubiquitination was associated with a dramatic increase in the level
      of antigen presentation. In conclusion, using the HBV surface protein as a model,
      we have identified a novel ubiquitin independent degradation pathway and
      determined that this pathway can have implications for antigen presentation and
      potentially viral pathogenesis.

PMID- 21969858
TI  - Global conservation priorities for marine turtles.
AB  - Where conservation resources are limited and conservation targets are diverse,
      robust yet flexible priority-setting frameworks are vital. Priority-setting is
      especially important for geographically widespread species with distinct
      populations subject to multiple threats that operate on different spatial and
      temporal scales. Marine turtles are widely distributed and exhibit intra-specific
      variations in population sizes and trends, as well as reproduction and
      morphology. However, current global extinction risk assessment frameworks do not
      assess conservation status of spatially and biologically distinct marine turtle
      Regional Management Units (RMUs), and thus do not capture variations in
      population trends, impacts of threats, or necessary conservation actions across
      individual populations. To address this issue, we developed a new assessment
      framework that allowed us to evaluate, compare and organize marine turtle RMUs
      according to status and threats criteria. Because conservation priorities can
      vary widely (i.e. from avoiding imminent extinction to maintaining long-term
      monitoring efforts) we developed a "conservation priorities portfolio" system
      using categories of paired risk and threats scores for all RMUs (n = 58). We
      performed these assessments and rankings globally, by species, by ocean basin,
      and by recognized geopolitical bodies to identify patterns in risk, threats, and
      data gaps at different scales. This process resulted in characterization of risk
      and threats to all marine turtle RMUs, including identification of the world's 11
      most endangered marine turtle RMUs based on highest risk and threats scores. This
      system also highlighted important gaps in available information that is crucial
      for accurate conservation assessments. Overall, this priority-setting framework
      can provide guidance for research and conservation priorities at multiple
      relevant scales, and should serve as a model for conservation status assessments
      and priority-setting for widespread, long-lived taxa.

PMID- 21969859
TI  - An image-free opto-mechanical system for creating virtual environments and
      imaging neuronal activity in freely moving Caenorhabditis elegans.
AB  - Non-invasive recording in untethered animals is arguably the ultimate step in the
      analysis of neuronal function, but such recordings remain elusive. To address
      this problem, we devised a system that tracks neuron-sized fluorescent targets in
      real time. The system can be used to create virtual environments by optogenetic
      activation of sensory neurons, or to image activity in identified neurons at high
      magnification. By recording activity in neurons of freely moving C. elegans, we
      tested the long-standing hypothesis that forward and reverse locomotion are
      generated by distinct neuronal circuits. Surprisingly, we found motor neurons
      that are active during both types of locomotion, suggesting a new model of
      locomotion control in C. elegans. These results emphasize the importance of
      recording neuronal activity in freely moving animals and significantly expand the
      potential of imaging techniques by providing a mean to stabilize fluorescent
      targets.

PMID- 21969860
TI  - Synergistic inhibition of endothelial cell proliferation, tube formation, and
      sprouting by cyclosporin A and itraconazole.
AB  - Pathological angiogenesis contributes to a number of diseases including cancer
      and macular degeneration. Although angiogenesis inhibitors are available in the
      clinic, their efficacy against most cancers is modest due in part to the
      existence of alternative and compensatory signaling pathways. Given that
      angiogenesis is dependent on multiple growth factors and a broad signaling
      network in vivo, we sought to explore the potential of multidrug cocktails for
      angiogenesis inhibition. We have screened 741 clinical drug combinations for the
      synergistic inhibition of endothelial cell proliferation. We focused specifically
      on existing clinical drugs since the re-purposing of clinical drugs allows for a
      more rapid and cost effective transition to clinical studies when compared to new
      drug entities. Our screen identified cyclosporin A (CsA), an immunosuppressant,
      and itraconazole, an antifungal drug, as a synergistic pair of inhibitors of
      endothelial cell proliferation. In combination, the IC(50) dose of each drug is
      reduced by 3 to 9 fold. We also tested the ability of the combination to inhibit
      endothelial cell tube formation and sprouting, which are dependent on two
      essential processes in angiogenesis, endothelial cell migration and
      differentiation. We found that CsA and itraconazole synergistically inhibit tube
      network size and sprout formation. Lastly, we tested the combination on human
      foreskin fibroblast viability as well as Jurkat T cell and HeLa cell
      proliferation, and found that endothelial cells are selectively targeted. Thus,
      it is possible to combine existing clinical drugs to synergistically inhibit in
      vitro models of angiogenesis. This strategy may be useful in pursuing the next
      generation of antiangiogenesis therapy.

PMID- 21969861
TI  - The worker honeybee fat body proteome is extensively remodeled preceding a major
      life-history transition.
AB  - Honeybee workers are essentially sterile female helpers that make up the majority
      of individuals in a colony. Workers display a marked change in physiology when
      they transition from in-nest tasks to foraging. Recent technological advances
      have made it possible to unravel the metabolic modifications associated with this
      transition. Previous studies have revealed extensive remodeling of brain, thorax,
      and hypopharyngeal gland biochemistry. However, data on changes in the abdomen is
      scarce. To narrow this gap we investigated the proteomic composition of abdominal
      tissue in the days typically preceding the onset of foraging in honeybee workers.
      In order to get a broader representation of possible protein dynamics, we used
      workers of two genotypes with differences in the age at which they initiate
      foraging. This approach was combined with RNA interference-mediated
      downregulation of an insulin/insulin-like signaling component that is central to
      foraging behavior, the insulin receptor substrate (irs), and with measurements of
      glucose and lipid levels. Our data provide new insight into the molecular
      underpinnings of phenotypic plasticity in the honeybee, invoke parallels with
      vertebrate metabolism, and support an integrated and irs-dependent association of
      carbohydrate and lipid metabolism with the transition from in-nest tasks to
      foraging.

PMID- 21969862
TI  - Characterization of Leishmania donovani aquaporins shows presence of subcellular
      aquaporins similar to tonoplast intrinsic proteins of plants.
AB  - Leishmania donovani, a protozoan parasite, resides in the macrophages of the
      mammalian host. The aquaporin family of proteins form important components of the
      parasite-host interface. The parasite-host interface could be a potential target
      for chemotherapy. Analysis of L. major and L. infantum genomes showed the
      presence of five aquaporins (AQPs) annotated as AQP9 (230aa), AQP putative
      (294aa), AQP-like protein (279aa), AQP1 (314aa) and AQP-like protein (596aa). We
      report here the structural modeling, localization and functional characterization
      of the AQPs from L. donovani. LdAQP1, LdAQP9, LdAQP2860 and LdAQP2870 have the
      canonical NPA-NPA motifs, whereas LdAQP putative has a non-canonical NPM-NPA
      motif. In the carboxyl terminal to the second NPA box of all AQPs except AQP1, a
      valine/alanine residue was found instead of the arginine. In that respect these
      four AQPs are similar to tonoplast intrinsic proteins in plants, which are
      localized to intracellular organelles. Confocal microscopy of L. donovani
      expressing GFP-tagged AQPs showed an intracellular localization of LdAQP9 and
      LdAQP2870. Real-time PCR assays showed expression of all aquaporins except
      LdAQP2860, whose level was undetectable. Three-dimensional homology modeling of
      the AQPs showed that LdAQP1 structure bears greater topological similarity to the
      aquaglyceroporin than to aquaporin of E. coli. The pore of LdAQP1 was very
      different from the rest in shape and size. The cavity of LdAQP2860 was highly
      irregular and undefined in geometry. For functional characterization, four AQP
      proteins were heterologously expressed in yeast. In the fps1Delta yeast cells,
      which lacked the key aquaglyceroporin, LdAQP1 alone displayed an osmosensitive
      phenotype indicating glycerol transport activity. However, expression of LdAQP1
      and LdAQP putative in a yeast gpd1Delta strain, deleted for glycerol production,
      conferred osmosensitive phenotype indicating water transport activity or
      aquaporin function. Our analysis for the first time shows the presence of
      subcellular aquaporins and provides structural and functional characterization of
      aquaporins in Leishmania donovani.

PMID- 21969863
TI  - Case series of fertility treatment in HIV-discordant couples (male positive,
      female negative): the Ontario experience.
AB  - The success of combination antiretroviral therapies for the treatment of human
      immunodeficiency virus (HIV) has resulted in prolonged life expectancy (over 40
      years from diagnosis) and an improved quality of life for people living with HIV.
      The risk of vertical HIV transmission during pregnancy has been reduced to less
      than 1%. As a result of these breakthroughs and as many of these individuals are
      of reproductive age, fertility issues are becoming increasingly important for
      this population. One population in which conception planning and reduction of
      horizontal HIV transmission warrants further research is HIV-discordant couples
      where the male partner is HIV-positive and the female partner is HIV-negative.
      Sperm washing is a technique carried out in a fertility clinic that separates HIV
      from the seminal fluid. Although sperm washing followed by intrauterine
      insemination significantly reduces the risk of horizontal HIV transmission, there
      has been limited access to the procedure in North America. Furthermore, little is
      known about the conception decision-making experiences of HIV-discordant couples
      who might benefit from sperm washing. Chart reviews and semi-structured
      interviews were completed with 12 HIV-discordant couples in Ontario, Canada.
      Couples were recruited through HIV clinics and one fertility clinic that offered
      sperm washing. Participants identified a number of factors that affected their
      decision-making around pregnancy planning. Access to sperm washing and other
      fertility services was an issue (cost, travel and few clinics). Participants
      identified a lack of information on the procedure (availability, safety). Sources
      of support (social networks, healthcare providers) were unevenly distributed,
      especially among those who did not disclose their HIV status to friends and
      family. Finally, the stigmatisation of HIV continues to have a negative affect on
      HIV-discordant couples and their intentions to conceive. Access to sperm washing
      and fertility service is significantly limited for this population and is
      accompanied with a number of challenges.

PMID- 21969864
TI  - Neural substrates for the motivational regulation of motor recovery after spinal
      cord injury.
AB  - It is believed that depression impedes and motivation enhances functional
      recovery after neuronal damage such as spinal-cord injury and stroke. However,
      the neuronal substrate underlying such psychological effects on functional
      recovery remains unclear. A longitudinal study of brain activation in the non
      human primate model of partial spinal-cord injury using positron emission
      tomography (PET) revealed a contribution of the primary motor cortex (M1) to the
      recovery of finger dexterity through the rehabilitative training. Here, we show
      that activity of the ventral striatum, including the nucleus accumbens (NAc),
      which plays a critical role in processing of motivation, increased and its
      functional connectivity with M1 emerged and was progressively strengthened during
      the recovery. In addition, functional connectivities among M1, the ventral
      striatum and other structures belonging to neural circuits for processing
      motivation, such as the orbitofrontal cortex, anterior cingulate cortex and
      pedunculopontine tegmental nucleus were also strengthened during the recovery.
      These results give clues to the neuronal substrate for motivational regulation of
      motor learning required for functional recovery after spinal-cord injury.

PMID- 21969865
TI  - PlGF repairs myocardial ischemia through mechanisms of angiogenesis,
      cardioprotection and recruitment of myo-angiogenic competent marrow progenitors.
AB  - RATIONALE: Despite preclinical success in regenerating and revascularizing the
      infarcted heart using angiogenic growth factors or bone marrow (BM) cells, recent
      clinical trials have revealed less benefit from these therapies than expected.
      OBJECTIVE: We explored the therapeutic potential of myocardial gene therapy of
      placental growth factor (PlGF), a VEGF-related angiogenic growth factor, with
      progenitor-mobilizing activity. METHODS AND RESULTS: Myocardial PlGF gene therapy
      improves cardiac performance after myocardial infarction, by inducing cardiac
      repair and reparative myoangiogenesis, via upregulation of paracrine anti
      apoptotic and angiogenic factors. In addition, PlGF therapy stimulated Sca
      1(+)/Lin(-) (SL) BM progenitor proliferation, enhanced their mobilization into
      peripheral blood, and promoted their recruitment into the peri-infarct borders.
      Moreover, PlGF enhanced endothelial progenitor colony formation of BM-derived SL
      cells, and induced a phenotypic switch of BM-SL cells, recruited in the infarct,
      to the endothelial, smooth muscle and cardiomyocyte lineage. CONCLUSIONS: Such
      pleiotropic effects of PlGF on cardiac repair and regeneration offer novel
      opportunities in the treatment of ischemic heart disease.

PMID- 21969866
TI  - A comprehensive expression profile of microRNAs in porcine pituitary.
AB  - MicroRNAs (miRNAs) are an abundant class of small RNAs that regulate expressions
      of most genes. miRNAs play important roles in the pituitary, the "master"
      endocrine organ.However, we still don't know which role miRNAs play in the
      development of pituitary tissue or how much they contribute to the pituitary
      function. By applying a combination of microarray analysis and Solexa sequencing,
      we detected a total of 450 miRNAs in the porcine pituitary. Verification with RT
      PCR showed a high degree of confidence for the obtained data. According to the
      current miRBase release17.0, the detected miRNAs included 169 known porcine
      miRNAs, 163 conserved miRNAs not yet identified in the pig, and 12 potentially
      new miRNAs not yet identified in any species, three of which were revealed using
      Northern blot. The pituitary might contain about 80.17% miRNA types belonging to
      the animal. Analysis of 10 highly expressed miRNAs with the Kyoto Encyclopedia of
      Genes and Genomes (KEGG) indicated that the enriched miRNAs were involved not
      only in the development of the organ but also in a variety of inter-cell and
      inner cell processes or pathways that are involved in the function of the organ.
      We have revealed the existence of a large number of porcine miRNAs as well as
      some potentially new miRNAs and established for the first time a comprehensive
      miRNA expression profile of the pituitary. The pituitary gland contains
      unexpectedly many miRNA types and miRNA actions are involved in important
      processes for both the development and function of the organ.

PMID- 21969867
TI  - A comparison of methods for classifying clinical samples based on proteomics
      data: a case study for statistical and machine learning approaches.
AB  - The discovery of protein variation is an important strategy in disease diagnosis
      within the biological sciences. The current benchmark for elucidating information
      from multiple biological variables is the so called "omics" disciplines of the
      biological sciences. Such variability is uncovered by implementation of
      multivariable data mining techniques which come under two primary categories,
      machine learning strategies and statistical based approaches. Typically proteomic
      studies can produce hundreds or thousands of variables, p, per observation, n,
      depending on the analytical platform or method employed to generate the data.
      Many classification methods are limited by an n?p constraint, and as such,
      require pre-treatment to reduce the dimensionality prior to classification.
      Recently machine learning techniques have gained popularity in the field for
      their ability to successfully classify unknown samples. One limitation of such
      methods is the lack of a functional model allowing meaningful interpretation of
      results in terms of the features used for classification. This is a problem that
      might be solved using a statistical model-based approach where not only is the
      importance of the individual protein explicit, they are combined into a readily
      interpretable classification rule without relying on a black box approach. Here
      we incorporate statistical dimension reduction techniques Partial Least Squares
      (PLS) and Principal Components Analysis (PCA) followed by both statistical and
      machine learning classification methods, and compared them to a popular machine
      learning technique, Support Vector Machines (SVM). Both PLS and SVM demonstrate
      strong utility for proteomic classification problems.

PMID- 21969868
TI  - Wood consumption by Geoffroyi's spider monkeys and its role in mineral
      supplementation.
AB  - Wood consumption is a rare behavior in frugivorous primates; however, it can be
      necessary for nutritional balancing as it may provide macro and/or micronutrients
      that are scarce in the most frequently eaten items (fruits). We tested this
      hypothesis in six spider monkey (Ateles geoffroyi) communities inhabiting
      continuous and fragmented rainforests in Lacandona, Mexico. We investigated the
      importance of both live and decayed wood in the diet of the monkeys, and assessed
      if wood consumption is related to the nutritional composition of these items. In
      general, wood consumption was focused on trees of Licania platypus
      (Chrysobalanaceae) and Ficus spp. (Moraceae), and was similar in continuous
      forest and in fragments (mean +/- SD; 24+/-20% vs 18+/-16% of total feeding time,
      respectively), but marginally higher in females than in males (16+/-14% vs 5+/
      4%, respectively). Live and decayed wood were both poorer in lipids, proteins,
      total nonstructural carbohydrates, and total digestible nutrients compared to
      mature and immature fruits. Moreover, decayed wood of L. platypus showed
      consistently higher levels of sodium and calcium compared to fruits. In
      conclusion, our findings suggest that wood from decaying trees of L. platypus and
      Ficus spp. and young branch piths of L. platypus represents an important source
      of sodium and/or calcium in the diet of spider monkeys, particularly in the case
      of females. The protection of decaying trees within forests and fragments is
      therefore necessary for the appropriate management and conservation of this
      endangered primate species.

PMID- 21969869
TI  - A new variant of the capsule 3 cluster occurs in Streptococcus pneumoniae from
      deceased wild chimpanzees.
AB  - The presence of new Streptococcus pneumoniae clones in dead wild chimpanzees from
      the Tai National Park, Cote d'Ivoire, with previous respiratory problems has been
      demonstrated recently by DNA sequence analysis from samples obtained from the
      deceased apes. In order to broadenour understanding on the relatedness of these
      pneumococcal clones to those from humans, the gene locus responsible for
      biosynthesis of the capsule polysaccharide (CPS) has now been characterized. DNA
      sequence analysis of PCR fragments identified a cluster named cps3(Tai)
      containing the four genes typical for serotype 3 CPS, but lacking a 5'-region of
      >=2 kb which is degenerated in other cps3 loci and not required for type 3
      biosynthesis. CPS3 is composed of a simple disaccharide repeat unit comprising
      glucose and glucuronic acid (GlcUA). The two genes ugd responsible for GlcUA
      synthesis and wchE encoding the type 3 synthase are essential for CPS3
      biosynthesis, whereas both, galU and the 3'-truncated gene pgm are not required
      due to the presence of homologues elsewhere in the genome. The DNA sequence of
      cps3(Tai) diverged considerably from those of other cps3 loci. Also, the gene
      pgm(Tai) represents a full length version with a nonsense mutation at codon 179.
      The two genes ugd(Tai) and wchE(Tai) including the promoter region were
      transformed into a nonencapsulated laboratory strain S. pneumoniae R6.
      Transformants which expressed type 3 capsule polysaccharide were readily
      obtained, documenting that the gene products are functional. In summary, the data
      indicate that cps3(Tai) evolved independent from other cps3 loci, suggesting the
      presence of specialized serotype 3 S. pneumoniae clones endemic to the Tai
      National Park area.

PMID- 21969870
TI  - Enrollment characteristics and risk behaviors of injection drug users
      participating in the Bangkok Tenofovir Study, Thailand.
AB  - BACKGROUND: The Bangkok Tenofovir Study was launched in 2005 to determine if pre
      exposure prophylaxis with tenofovir will reduce the risk of HIV infection among
      injecting drug users (IDUs). We describe recruitment, screening, enrollment, and
      baseline characteristics of study participants and contrast risk behavior of
      Tenofovir Study participants with participants in the 1999-2003 AIDSVAX B/E
      Vaccine Trial. METHODS: The Bangkok Tenofovir Study is an ongoing, phase-3,
      randomized, double-blind, placebo-controlled, HIV pre-exposure prophylaxis trial
      of daily oral tenofovir. The Tenofovir Study and the Vaccine Trial were conducted
      among IDUs at 17 drug-treatment clinics in Bangkok. Tenofovir Study sample size
      was based on HIV incidence in the Vaccine Trial. Standardized questionnaires were
      used to collect demographic, risk behavior, and incarceration data. The Tenofovir
      Study is registered with ClinicalTrials.gov, number--NCT00119106. RESULTS: From
      June 2005 through July 2010, 4094 IDUs were screened and 2413 enrolled in the
      Bangkok Tenofovir Study. The median age of enrolled participants was 31 years
      (range, 20-59), 80% were male, and 63% reported they injected drugs during the 3
      months before enrollment. Among those who injected, 53% injected methamphetamine,
      37% midazolam, and 35% heroin. Tenofovir Study participants were less likely to
      inject drugs, inject daily, or share needles (all, p<0.001) than Vaccine Trial
      participants. DISCUSSION: The Bangkok Tenofovir Study has been successfully
      launched and is fully enrolled. Study participants are significantly less likely
      to report injecting drugs and sharing needles than participants in the 1999-2003
      AIDSVAX B/E Vaccine Trial suggesting HIV incidence will be lower than expected.
      In response, the Bangkok Tenofovir Study enrollment was increased from 1600 to
      2400 and the study design was changed from a defined 1-year follow-up period to
      an endpoint-driven design. Trial results demonstrating whether or not daily oral
      tenofovir reduces the risk of HIV infection among IDUs are expected in 2012.

PMID- 21969871
TI  - Impaired striatal Akt signaling disrupts dopamine homeostasis and increases
      feeding.
AB  - BACKGROUND: The prevalence of obesity has increased dramatically worldwide. The
      obesity epidemic begs for novel concepts and therapeutic targets that cohesively
      address "food-abuse" disorders. We demonstrate a molecular link between
      impairment of a central kinase (Akt) involved in insulin signaling induced by
      exposure to a high-fat (HF) diet and dysregulation of higher order circuitry
      involved in feeding. Dopamine (DA) rich brain structures, such as striatum,
      provide motivation stimuli for feeding. In these central circuitries, DA
      dysfunction is posited to contribute to obesity pathogenesis. We identified a
      mechanistic link between metabolic dysregulation and the maladaptive behaviors
      that potentiate weight gain. Insulin, a hormone in the periphery, also acts
      centrally to regulate both homeostatic and reward-based HF feeding. It regulates
      DA homeostasis, in part, by controlling a key element in DA clearance, the DA
      transporter (DAT). Upon HF feeding, nigro-striatal neurons rapidly develop
      insulin signaling deficiencies, causing increased HF calorie intake.
      METHODOLOGY/PRINCIPAL FINDINGS: We show that consumption of fat-rich food impairs
      striatal activation of the insulin-activated signaling kinase, Akt. HF-induced
      Akt impairment, in turn, reduces DAT cell surface expression and function,
      thereby decreasing DA homeostasis and amphetamine (AMPH)-induced DA efflux. In
      addition, HF-mediated dysregulation of Akt signaling impairs DA-related behaviors
      such as (AMPH)-induced locomotion and increased caloric intake. We restored nigro
      striatal Akt phosphorylation using recombinant viral vector expression
      technology. We observed a rescue of DAT expression in HF fed rats, which was
      associated with a return of locomotor responses to AMPH and normalization of HF
      diet-induced hyperphagia. CONCLUSIONS/SIGNIFICANCE: Acquired disruption of brain
      insulin action may confer risk for and/or underlie "food-abuse" disorders and the
      recalcitrance of obesity. This molecular model, thus, explains how even short
      term exposure to "the fast food lifestyle" creates a cycle of disordered eating
      that cements pathological changes in DA signaling leading to weight gain and
      obesity.

PMID- 21969872
TI  - Cranial growth and variation in edmontosaurs (Dinosauria: Hadrosauridae):
      implications for latest Cretaceous megaherbivore diversity in North America.
AB  - The well-sampled Late Cretaceous fossil record of North America remains the only
      high-resolution dataset for evaluating patterns of dinosaur diversity leading up
      to the terminal Cretaceous extinction event. Hadrosaurine hadrosaurids
      (Dinosauria: Ornithopoda) closely related to Edmontosaurus are among the most
      common megaherbivores in latest Campanian and Maastrichtian deposits of western
      North America. However, interpretations of edmontosaur species richness and
      biostratigraphy have been in constant flux for almost three decades, although the
      clade is generally thought to have undergone a radiation in the late
      Maastrichtian. We address the issue of edmontosaur diversity for the first time
      using rigorous morphometric analyses of virtually all known complete edmontosaur
      skulls. Results suggest only two valid species, Edmontosaurus regalis from the
      late Campanian, and E. annectens from the late Maastrichtian, with previously
      named taxa, including the controversial Anatotitan copei, erected on hypothesized
      transitional morphologies associated with ontogenetic size increase and
      allometric growth. A revision of North American hadrosaurid taxa suggests a
      decrease in both hadrosaurid diversity and disparity from the early to late
      Maastrichtian, a pattern likely also present in ceratopsid dinosaurs. A decline
      in the disparity of dominant megaherbivores in the latest Maastrichtian interval
      supports the hypothesis that dinosaur diversity decreased immediately preceding
      the end Cretaceous extinction event.

PMID- 21969873
TI  - Hematological changes as prognostic indicators of survival: similarities between
      Gottingen minipigs, humans, and other large animal models.
AB  - BACKGROUND: The animal efficacy rule addressing development of drugs for selected
      disease categories has pointed out the need to develop alternative large animal
      models. Based on this rule, the pathophysiology of the disease in the animal
      model must be well characterized and must reflect that in humans. So far,
      manifestations of the acute radiation syndrome (ARS) have been extensively
      studied only in two large animal models, the non-human primate (NHP) and the
      canine. We are evaluating the suitability of the minipig as an additional large
      animal model for development of radiation countermeasures. We have previously
      shown that the Gottingen minipig manifests hematopoietic ARS phases and symptoms
      similar to those observed in canines, NHPs, and humans. PRINCIPAL FINDINGS: We
      establish here the LD50/30 dose (radiation dose at which 50% of the animals
      succumb within 30 days), and show that at this dose the time of nadir and the
      duration of cytopenia resemble those observed for NHP and canines, and mimic
      closely the kinetics of blood cell depletion and recovery in human patients with
      reversible hematopoietic damage (H3 category, METREPOL approach). No signs of GI
      damage in terms of diarrhea or shortening of villi were observed at doses up to
      1.9 Gy. Platelet counts at days 10 and 14, number of days to reach critical
      platelet values, duration of thrombocytopenia, neutrophil stress response at 3
      hours and count at 14 days, and CRP-to-platelet ratio were correlated with
      survival. The ratios between neutrophils, lymphocytes and platelets were
      significantly correlated with exposure to irradiation at different time
      intervals. SIGNIFICANCE: As a non-rodent animal model, the minipig offers a
      useful alternative to NHP and canines, with attractive features including ARS
      resembling human ARS, cost, and regulatory acceptability. Use of the minipig may
      allow accelerated development of radiation countermeasures.

PMID- 21969874
TI  - Video-rate bioluminescence imaging of matrix metalloproteinase-2 secreted from a
      migrating cell.
AB  - BACKGROUND: Matrix metalloproteinase-2 (MMP-2) plays an important role in cancer
      progression and metastasis. MMP-2 is secreted as a pro-enzyme, which is activated
      by the membrane-bound proteins, and the polarized distribution of secretory and
      the membrane-associated MMP-2 has been investigated. However, the real-time
      visualizations of both MMP-2 secretion from the front edge of a migration cell
      and its distribution on the cell surface have not been reported.
      METHODOLOGY/PRINCIPAL FINDINGS: The method of video-rate bioluminescence imaging
      was applied to visualize exocytosis of MMP-2 from a living cell using Gaussia
      luciferase (GLase) as a reporter. The luminescence signals of GLase were detected
      by a high speed electron-multiplying charge-coupled device camera (EM-CCD camera)
      with a time resolution within 500 ms per image. The fusion protein of MMP-2 to
      GLase was expressed in a HeLa cell and exocytosis of MMP-2 was detected in a few
      seconds along the leading edge of a migrating HeLa cell. The membrane-associated
      MMP-2 was observed at the specific sites on the bottom side of the cells,
      suggesting that the sites of MMP-2 secretion are different from that of MMP-2
      binding. CONCLUSIONS: We were the first to successfully demonstrate secretory
      dynamics of MMP-2 and the specific sites for polarized distribution of MMP-2 on
      the cell surface. The video-rate bioluminescence imaging using GLase is a useful
      method to investigate distribution and dynamics of secreted proteins on the whole
      surface of polarized cells in real time.

PMID- 21969875
TI  - High prevalence of self-reported undiagnosed HIV despite high coverage of HIV
      testing: a cross-sectional population based sero-survey in South Africa.
AB  - OBJECTIVES: To measure HIV prevalence and uptake of HIV counseling and testing
      (HCT) in a peri-urban South African community. To assess predictors for previous
      HIV testing and the association between the yield of previously undiagnosed HIV
      and time of last negative HIV test METHODS: A random sample of 10% of the adult
      population (>=15 years) were invited to attend a mobile HCT service. Study
      procedures included a questionnaire, HIV testing and CD4 counts. Predictors for
      previous testing were determined using a binominal model. RESULTS: 1,144 (88.0%)
      of 1,300 randomly selected individuals participated in the study. 71.0% (68.3
      73.6) had previously had an HIV test and 37.5% (34.6-40.5) had tested in the past
      12 months. Men, migrants and older (>35 years) and younger (<20 years)
      individuals were less likely to have had a previous HIV test. Overall HIV
      prevalence was 22.7 (20.3-25.3) with peak prevalence of 41.8% (35.8-47.8) in
      women aged 25.1-35 years and 37.5% (26.7-48.3) in men aged 25.1-45 years.
      Prevalence of previously undiagnosed HIV was 10.3% (8.5-12.1) overall and 4.5%
      (2.3-6.6), 8.0% (CI 3.9-12.0) and 20.0% (13.2-26.8) in individuals who had their
      most recent HIV test within 1, 1-2 and more than 2 years prior to the survey.
      CONCLUSION: The high burden of undiagnosed HIV in individuals who had recently
      tested underscores the importance of frequent repeat testing at least annually.
      The high prevalence of previously undiagnosed HIV in individuals reporting a
      negative test in the 12 months preceding the survey indicates a very high
      incidence. Innovative prevention strategies are needed.

PMID- 21969876
TI  - Reproductive benefit of oxidative damage: an oxidative stress "malevolence"?
AB  - High levels of reactive oxygen species (ROS) compared to antioxidant defenses are
      considered to play a major role in diverse chronic age-related diseases and
      aging. Here we present an attempt to synthesize information about proximate
      oxidative processes in aging (relevant to free radical or oxidative damage
      hypotheses of aging) with an evolutionary scenario (credited here to Dawkins
      hypotheses) involving tradeoffs between the costs and benefits of oxidative
      stress to reproducing organisms. Oxidative stress may be considered a biological
      imperfection; therefore, the Dawkins' theory of imperfect adaptation of beings to
      environment was applied to the role of oxidative stress in processes like famine
      and infectious diseases and their consequences at the molecular level such as
      mutations and cell signaling. Arguments are presented that oxidative damage is
      not necessarily an evolutionary mistake but may be beneficial for reproduction;
      this may prevail over its harmfulness to health and longevity in evolution. Thus,
      Dawkins' principle of biological "malevolence" may be an additional biological
      paradigm for explaining the consequences of oxidative stress.

PMID- 21969878
TI  - Binge ethanol intake in chronically exposed rat liver decreases LDL-receptor and
      increases angiotensinogen gene expression.
AB  - AIM: To investigated the status of low-density lipoprotein (LDL)-receptor and
      angiotensionogen gene expression in rats treated chronically with ethanol
      followed by binge administration, a model that mimics the human scenario.
      METHODS: Rats were chronically treated with ethanol in liquid diet for 4 wk
      followed by a single binge mode of ethanol administration (5 mg/kg body weight).
      Samples were processed 4 h after binge ethanol administration (chronic ethanol
      binge). Control rats were fed isocaloric diet. In the control for binge, ethanol
      was replaced by water. Expression of mRNA for angiotensinogen, c-fos and LDL
      receptor, and nuclear accumulation of phospho-extracellular regulated kinases
      (ERK)1/2 and ERK1/2 protein were examined. RESULTS: Binge ethanol administration
      in chronically treated rats caused increase in steatosis and necrosis. Chronic
      ethanol alone had negligible effect on mRNA levels of LDL-receptor, or on the
      levels of nuclear ERK1/2 and phospho-ERK1/2. But, chronic ethanol followed by
      binge caused a decrease in LDL-receptor mRNA, and also decreased the levels of
      ERK1/2 and phospho-ERK1/2 in the nuclear compartment. On the other hand, chronic
      ethanol-binge increased mRNA expression of angiotensinogen and c-fos. CONCLUSION:
      Binge ethanol after chronic exposure, causes transcriptional dysregulation of LDL
      receptor and angiotensinogen genes, both cardiovascular risk factors.

PMID- 21969879
TI  - Simultaneous occurrence of malignant fibrous histiocytoma and hepatocellular
      carcinoma in cirrhotic liver: A case report.
AB  - Primary hepatic malignant fibrous histiocytoma (MFH) is rarely encountered. There
      have been no reports to date of hepatic MFH associated with liver cirrhosis. The
      presence of liver cirrhosis is considered an adjunctive feature favoring
      sarcomatoid hepatocellular carcinoma (HCC) in the diagnosis of spindle cell
      tumors in liver. We describe here a 59-year-old man with liver cirrhosis due to
      hepatitis B virus infection 20 years ago. On abdominal computed tomography
      scanning, two distinct hepatic masses were identified in the background of
      cirrhosis, which had different radiological features from conventional HCC. He
      underwent segmentectomy for removal of the tumors. The pathological examination
      of surgically resected specimen revealed the large malignant spindle cell tumor
      and small conventional HCC. Additional tissue sampling and immunohistochemical
      stainings demonstrated that the spindle cell tumor was consistent with MFH. On
      the post-operative follow-up for 21 mo, a round mass showing similar radiological
      findings for the previous MFH was appeared on the surface of resection margin,
      suggesting the recurrence. Despite its rarity, hepatic MFH should be considered
      during differential diagnosis, even in cirrhotic patients, and extensive tissue
      sampling and immunohistochemical analyses are necessary in the diagnosis of
      hepatic spindle cell tumors.

PMID- 21969877
TI  - Terpenoids as potential chemopreventive and therapeutic agents in liver cancer.
AB  - Despite significant advances in medicine, liver cancer, predominantly
      hepatocellular carcinoma remains a major cause of death in the United States as
      well as the rest of the world. As limited treatment options are currently
      available to patients with liver cancer, novel preventive control and effective
      therapeutic approaches are considered to be reasonable and decisive measures to
      combat this disease. Several naturally occurring dietary and non-dietary
      phytochemicals have shown enormous potential in the prevention and treatment of
      several cancers, especially those of the gastrointestinal tract. Terpenoids, the
      largest group of phytochemicals, traditionally used for medicinal purposes in
      India and China, are currently being explored as anticancer agents in clinical
      trials. Terpenoids (also called "isoprenoids") are secondary metabolites
      occurring in most organisms, particularly plants. More than 40 000 individual
      terpenoids are known to exist in nature with new compounds being discovered every
      year. A large number of terpenoids exhibit cytotoxicity against a variety of
      tumor cells and cancer preventive as well as anticancer efficacy in preclinical
      animal models. This review critically examines the potential role of naturally
      occurring terpenoids, from diverse origins, in the chemoprevention and treatment
      of liver tumors. Both in vitro and in vivo effects of these agents and related
      cellular and molecular mechanisms are highlighted. Potential challenges and
      future directions involved in the advancement of these promising natural
      compounds in the chemoprevention and therapy of human liver cancer are also
      discussed.

PMID- 21969881
TI  - Heartsink encounters: a qualitative study of end-of-life care in out-of-hours
      general practice.
AB  - OBJECTIVES: We aimed to establish how prepared GPs who work regular out-of-hours
      shifts feel when dealing with end-of-life issues in palliative care patients,
      what they thought about seeing such patients and whether they considered
      themselves emotionally equipped to do so. DESIGN: Semi-structured interviews were
      conducted with GPs who worked regular out-of-hours shifts. A detailed analysis of
      transcripts using Interpretative Phenomenological Analysis was undertaken.
      SETTING: South Wales. PARTICIPANTS: GPs employed by the local health board's out
      of-hours service were contacted. MAIN OUTCOME MEASURES: All interview data were
      analysed systematically and statements that reflected emotional impact and strain
      were highlighted, coded and interpreted within their context. RESULTS: GPs
      expressed unease and used terms such as 'heartsink', when having to deal with
      palliative care issues out-of-hours. Heartsink in this context referred to the
      subjective experience of the clinician. Emotional 'housekeeping', i.e. looking
      after oneself after emotionally-charged encounters, was felt to be a very
      important process and GPs used a range of coping mechanisms, including reflective
      time, sharing with peers, compartmentalisation and personal empathy to deal with
      stress. CONCLUSION: The emotional effects of palliative care encounters on out-of
      hours GPs should not be underestimated. Our interpretation distinguished the term
      'heartsink' from its usual context, the 'heartsink patient', to a different
      meaning, that of the imminent palliative care encounter triggering a sensation of
      heartsink for some out-of-hours doctors. Therefore, the term 'heartsink
      encounter', rather than heartsink patient, seemed more fitting. Pressed services
      may encourage a culture where discussion or debrief with a colleague after a
      palliative care encounter is not perceived as a practical option. This may
      contribute to work-related burnout in this group of doctors and out-of-hours
      collaboratives need to be aware of this issue, when planning their services.

PMID- 21969880
TI  - The views of patients and the general public about expensive anti-cancer drugs in
      the NHS: a questionnaire-based study.
AB  - OBJECTIVES: To determine the views of patients and members of the public about
      who should pay for expensive new cancer drugs not recommended by the National
      Institute for Health and Clinical Excellence (NICE). DESIGN: A study-specific
      questionnaire was used to elicit the views of patients and the general public
      between April and June 2010. It examined whether participants thought patients
      should be told about all possible cancer treatments, if the NHS should always
      fund non-NICE recommended drugs and attitudes towards self-funding/co-payments.
      The influence of sociodemographic factors on responses was also examined.
      SETTING: Oncology clinics in Sussex and various locations including old persons'
      lunch clubs, parks, sports venues and support groups. PARTICIPANTS: Two hundred
      and 10 patients with common solid tumours, and 416 members of the general public
      MAIN OUTCOME MEASURES: Frequencies of responses to items regarding payments for
      expensive anti-cancer drugs stratified by sociodemographic factors and comparison
      of responses between patients and members of the public. RESULTS: Most
      respondents (70% [147/210] of patients and 64% [266/416] of the general public)
      had heard of NICE. Both groups believed that doctors should tell patients about
      all available cancer treatments even if the NHS cannot pay (94%, 196/208; 93%,
      388/415). However, only 49% (101/207) of patients and 36% (146/409) of the public
      believed that the NHS should always fund all new cancer drugs that have failed
      health technology assessments. Strong predictors of willingness to purchase
      expensive new cancer drugs included younger age (<45 years), sex (female) and
      higher educational level. CONCLUSION: The general population appear realistic
      about the difficulties of providing funding for expensive new drugs. A
      communication skills training course has been developed to help clinicians with
      these difficult consultations.

PMID- 21969882
TI  - Design, development and validation of the RedBrick Health Assessment: a
      questionnaire-based study.
AB  - OBJECTIVES: Health risk assessment (HRA) questionnaires have become a popular
      tool to help quantify health issues within populations. Over the last decade HRAs
      have increasingly been delivered in the online environment. The objective of this
      study was to create and validate an HRA that is optimized for delivery via the
      Internet. DESIGN: After an iterative process of user testing and interface design
      the RedBrick Health Assessment (RBHA) was validated against known domain specific
      questionnaires with 464 working Americans, and with medical claims data from over
      25,000 employees. SETTING: All consumer testing, data capture and analysis
      occurred at the offices of RedBrick Health Corporation, Minneapolis, USA and via
      a secure online portal. PARTICIPANTS: Individuals in full-time employment in the
      USA, who were between 18 and 65 years of age at the time inquiry. MAIN OUTCOME
      MEASURES: Correlation of the included RBHA domains with the output from known
      gold standard health question sets for each assessed health domain. RESULTS: The
      iterative development process employed in creating the RBHA produced a tool that
      had a high degree of user acceptability. The domains demonstrated good
      correlations with relevant gold standard questionnaire measures, good internal
      consistency, and acceptable sensitivity and specificity when compared to gold
      standard risk stratification and high-risk classification (specificity of domains
      ranged from 76-94%). A test-retest correlation co-efficient of 0.7, or greater,
      was achieved 8 weeks after initial completion. CONCLUSIONS: The RBHA is a new
      breed of HRA that has been specifically developed for capturing health status
      information in an online environment. At its heart is user centricity and this
      focus has enabled the creation of a tool that is not only highly engaging but
      also captures accurate and robust health status information.

PMID- 21969883
TI  - Unusual presentation of dysphagia caused by bronchogenic cyst.

PMID- 21969884
TI  - An important but easily overlooked medical complication of multiple trauma.

PMID- 21969885
TI  - Synergistic gangrene of the breast in a patient with type 2 diabetes.

PMID- 21969886
TI  - Complementary and Alternative Medicine: Where do we stand in the 21 century?

PMID- 21969887
TI  - The Role of Pharmacokinetics and Pharmacodynamics in Early Drug Development with
      reference to the Cyclin-dependent Kinase (Cdk) Inhibitor - Roscovitine.
AB  - Pharmacokinetics, pharmacodynamics and pharmacogenetics play an important role in
      drug discovery and contribute to treatment success. This is an essential issue in
      cancer treatment due to its high toxicity. During the last decade, cyclin
      dependent kinase inhibitors were recognised as a new class of compounds that was
      introduced for the treatment of several diseases including cancer. Cyclin
      dependent kinases (Cdks) play a key role in the regulation of cell cycle
      progression and ribonucleic acid transcription. Deregulation of Cdks has been
      associated with several malignancies, neurodegenerative disorders, viral and
      protozoa infections, glomerulonephritis and inflammatory diseases. (R)
      roscovitine is a synthetic tri-substituted purine that inhibits selectively Cdk1,
      2, 5, 7 and 9. Roscovitine has shown promising cytotoxicity in cell lines and
      tumor xenografts. In this paper, we present several aspects of pharmacokinetics
      (PK) and pharmacodynamics (PD) of roscovitine. We present also some of our
      investigations including bioanalysis, haematotoxicity, age dependent kinetics, PK
      and effects on Cdks in the brain. Unfavourable kinetic parameters in combination
      with poor distribution to the bone marrow compartment could explain the absence
      of myelosuppression in vivo despite the efficacy in vitro. Higher plasma and
      brain exposure and longer elimination half-life found in rat pups compared to
      adult rats may indicate that roscovitine can be a potential candidate for the
      treatment of brain tumours in children. Cdk5 inhibition and Erk1/2 activation
      that was detected in brain of rat pups may suggest the use of roscovitine in
      neurodegenerative diseases. Early pharmacokinetic/pharmacodynamic studies are
      important issues in drug discovery and may affect further development of
      promising drug candidates.

PMID- 21969889
TI  - Sent to Explore, Conquer and Heal: History of the evolution of biomedicine in
      Oman during the 19 century.
AB  - During the past four decades, Oman has transformed into a modern state with
      remarkable changes in all fields, including public health and the provision of
      medical services. Little attention has been paid so far to the history of the
      development of biomedicine in Oman. A history of healing practices, just like
      clinical patient histories, helps to diagnose problems, plan interventions and
      predict their future within a dynamic context. This study is the first to explore
      the beginnings and evolution of biomedicine in Oman during the 19(th) century,
      categorising it into three eras: from the casual system offered by occasional
      visiting biomedical practitioners to the more organised, but limited, British
      military hospital and, finally, to public missionary medical care toward the end
      of the 19(th) century. The study concludes by recommending further focus on
      medical humanities, including the history of medicine, as a contributing factor
      to improve and sustain the art and practice of medicine within the existing Omani
      health care system.

PMID- 21969888
TI  - Oral Manifestations and Complications of Diabetes Mellitus: A review.
AB  - Diabetes mellitus is a chronic disease affecting all age groups. It is one of the
      leading causes of mortality and morbidity worldwide. Many chronic macrovascular
      and microvascular complications of diabetes have been reported in the literature
      with few reports about oral complications. This article aims to review and
      increase the awareness of oral manifestations and complications of diabetes
      mellitus and to stimulate research on the subject. It treats in depth some of the
      complications such as periodontal disease, fungal infection and salivary
      dysfunction while other complications are mentioned briefly.

PMID- 21969890
TI  - To be or not to be exposed to direct sunlight: vitamin d deficiency in oman.
AB  - Only small amounts of vitamin D come from dietary sources as it is mainly
      synthesised in the skin from the ultraviolet B (UVB) fraction of sunlight if the
      person is sufficiently exposed to direct sunlight. Vitamin D deficiency has been
      well documented in Oman. The "2004 Oman National Micronutrients Survey" and other
      recent studies revealed that vitamin D3 stores are low among healthy Omani
      females of childbearing age and pregnant women. This situation is confusing as
      Oman is known to be one of the sunniest countries in the world. However, it is
      known that most Omani women are well covered and for various reasons avoid sun
      exposure. The article addresses a question about the balance that should be
      maintained between excessive sun exposure that leads to an increased risk of skin
      cancer, and healthy exposure that provides sufficient ultraviolet radiation (UVR)
      to maintain adequate vitamin D levels. In order to avoid vitamin D deficiency,
      sun exposure or protection messages must be tailored according to different
      situations, in recognition of the complex combination of personal, cultural and
      social factors that affect vitamin D synthesis in the skin.

PMID- 21969891
TI  - Incentives for better performance in health care.
AB  - Incentives for better performance in health care have several modes and methods.
      They are designed to motivate and encourage people to perform well and improve
      their outcomes. They may include monetary or non-monetary incentives and may be
      applied to consumers, individual providers or institutions. One such model is the
      Pay-for-Performance system. In this system, beneficiaries are compared with one
      another based on a set of performance indicators and those that achieve a high
      level of performance are rewarded financially. This system is meant to recognise
      and primarily to reward high performers. Its goal is to encourage beneficiaries
      to strive for better performance. This system has been applied in several
      countries and for several recipients and settings. Early indications show that
      this system has had mixed effects on performance.

PMID- 21969892
TI  - Factors Affecting the Quality of Diabetic Care in Primary Care Settings in Oman:
      A qualitative study on patients' perspectives.
AB  - OBJECTIVES: The quality of services delivered to type 2 diabetic patients in
      primary health care has an important impact on long-term outcomes. The aim of
      this study is to explore diabetic patients' views of factors affecting quality of
      diabetic services delivered in primary care in Oman, a developing country with a
      high burden of diabetes. METHODS: Semi-structured face to face interviews were
      conducted with 19 type 2 diabetic patients recruited from four selected primary
      healthcare centres (PHCs) in Muscat region, the capital city of Oman. A framework
      approach was used to analyse the qualitative data. RESULTS: PARTICIPANTS
      IDENTIFIED SEVERAL FACTORS WHICH COULD AFFECT THE QUALITY OF DIABETIC SERVICES
      PROVIDED IN PHCS: delays in the follow-up process; lack of continuity of care;
      diabetes educational materials unavailable in waiting areas; shortage of Omani
      nurses able to speak the patients' language; inadequate explanations from the
      attending primary care physician (PCP); under involvement of dieticians in
      patient management; delays in provision of laboratory results; inadequate
      supplies of diabetic medication between appointments, and long waits to see
      ophthalmologists. CONCLUSION: Several factors were identified by diabetic
      patients that may influence the quality of diabetic services provided in the PHC
      setting in Oman. Health care professionals and decision makers in the Ministry of
      Health (MOH) and other health care sectors in Oman should consider patients'
      views and concerns in order to improve the quality of diabetic care services in
      primary health care.

PMID- 21969893
TI  - Time trends and geographical distribution of childhood leukaemia in basrah, iraq,
      from 2004 to 2009.
AB  - OBJECTIVES: This study aimed to assess the incidence and trend of childhood
      leukaemia in Basrah. METHODS: This was a hospital-based cancer registry study
      carried out at the Pediatric Oncology Ward, Maternity & Children's Hospital and
      other institutes in Basrah, Iraq. All children with leukaemia, aged 0 to 14 years
      diagnosed and registered in Basrah from January 2004 to December 2009 were
      included in the study. Their records were retrieved and studied. The pattern of
      childhood leukaemia by year of diagnosis, age at diagnosis, morphological
      subtypes, and geographical distribution was analysed. Rates of childhood
      leukaemia over time were calculated for six years using standard linear
      regression. RESULTS: The total number of cases of childhood leukaemia was 181.
      The number of cases ranged from 21 in year 1, to 31 in the final year reaching a
      peak of 39 in 2006. Leukaemia rates did not change over the study period (test
      for trend was not significant, P = 0.81). The trend line shows a shift towards
      younger children (less than 5 years). The commonest types of leukaemia were acute
      lymphoblastic leukaemia (ALL), then acute myeloid leukaemia (AML) and finally
      chronic myeloid leukaemia (CML). CONCLUSION: Annual rates of childhood leukaemia
      in Basrah were similar to those in other countries with a trend towards younger
      children. This raises the question about the effect of environmental catastrophes
      in the alteration of some specific rates of childhood leukaemia, rather than the
      overall incidence rate. There is a need for further epidemiological studies to
      understand the aetiology of childhood leukaemia in Basrah.

PMID- 21969894
TI  - Effects of pranayam breathing on respiratory pressures and sympathovagal balance
      of patients with chronic airflow limitation and in control subjects.
AB  - OBJECTIVES: The objective of this study was to compare the effects of Pranayam
      breathing on respiratory muscle strength measured as maximum expiratory and
      inspiratory pressures (MEP and MIP) and relevant spirometry parameters in
      patients with chronic obstructive pulmonary disease (COPD) and in control
      subjects, and on the sympatho-vagal balance in both the groups. METHODS: The
      research was performed in the Clinical Physiology Department, Sultan Qaboos
      University Hospital, Oman. Eleven patients (mean age 43.91 +/- 20.56 yr; mean BMI
      21.9 +/- 5.5 kg/m(2)) and 6 controls (43.5 +/- 14.6yr; 25.4 +/- 3.2 kg/m(2))
      learnt and practised Pranayam. Their respiratory and cardiovascular parameters
      were recorded. Their respiratory "well being" was noted as a visual analogue
      score (VAS). The respiratory parameters were expressed as a percentage change of
      predicted values. RESULTS: Patients' respiratory parameters were significantly
      lower than those of controls. Patients' maximum respiratory pressures did not
      improve after Pranayam; however, they showed significant improvement in VAS 5.4
      +/- 2.4 to 7.2 +/- 1.2 (P < 0.03). Controls showed significant increase in MIP
      after Pranayam exercises. There were no changes in other spirometry indices.
      Controls showed significant increase in their systolic blood pressure and stroke
      index after exercise. The vago-sympathetic balance shifted towards sympathetic in
      both patients and controls after exercise. CONCLUSION: The improvement in MIP in
      controls indicated the positive effect of Pranayam exercise; however, it may not
      be an adequately stressful exercise to produce changes in the respiratory
      parameters of COPD patients. The increase in VAS in patients suggested
      improvement in respiratory distress and quality of life.

PMID- 21969895
TI  - Clinical and Therapeutic Profiles of Heart Failure Patients admitted to a
      Tertiary Hospital, Aseer Region, Saudi Arabia.
AB  - OBJECTIVES: This study aimed to investigate the clinical and therapeutic profiles
      of heart failure (HF) cases admitted to Aseer Central Hospital (ACH), Saudi
      Arabia. METHODS: A retrospective cohort of 300 consecutive patients admitted with
      the diagnosis of HF to ACH from 1 June 2007 to 31 May 2009 were included in the
      study. Data on demographic variables, aetiologic factors, risk factors, and
      therapeutic profiles of patients with HF were collected and analysed. RESULTS:
      The patients' mean age was 67.4 +/- 13.7 years and 68.7% of them were male. The
      commonest aetiologies for HF were ischaemic heart disease (IHD) and hypertension
      in 38.3% and 33.3% of patients, respectively. A total of 61.3% of patients were
      diabetics. Other risk factors for HF included renal failure in 9.7%, atrial
      fibrillation in 13%, and anaemia in 48.3% of patients. Echocardiography was
      performed in 98.7% of cases: the average ejection fraction (EF) was 33% +/- 17.
      Angiotensin converting enzyme inhibitors (ACEI) or angiotensin 2 receptor
      blockers were used in 68.3% of cases, beta-blockers in 51.6% of cases and digoxin
      in 28.3% of cases. CONCLUSION: The major causes of HF in our study were IHD and
      hypertension. Diabetes and anaemia were common risk factors. The cohort
      constituted an intermediate HF risk group (ejection fraction (EF) 33%). Important
      therapeutic agents like angiotensin converting enzyme inhibitor I, beta-blockers
      and digoxin were underutilised. Fostering such therapy in practice will lead to a
      better outcome in the management of HF patients. Anaemia was a significant risk
      factor in our HF patients and should be managed properly.

PMID- 21969896
TI  - Effects of hydrogen sulphide on the isolated perfused rat heart.
AB  - OBJECTIVES: Hydrogen sulphide has been identified as a gas signalling molecule in
      the body, and has previously been shown to have vasorelaxant properties. The aim
      of the study was to investigate the effects of sodium hydrosulphide (NaHS), a
      hydrogen sulphide donor, on heart rate (HR), left ventricular developed pressure
      (LVDP) and coronary flow (CF) in the isolated perfused rat heart. METHODS: A
      Langendorff isolated heart preparation was used to investigate the effect of a
      dose range of sodium hydrosulphide, in the presence and absence of inhibitors, on
      heart rate, left ventricular developed pressure and coronary flow. RESULTS:
      Sodium hydrosulphide caused a significant decrease in heart rate at a
      concentration of 10-3 M (P <0.001). This decrease was partially inhibited by
      glibenclamide, a K(ATP) channel blocker (P <0.05); L-NAME, a nitric oxide
      synthase inhibitor (P <0.001), and methylene blue (P <0.001), but not by H-89, a
      protein kinase A inhibitor. Sodium hydrosulphide significantly increased coronary
      flow at concentrations of 10-4 - 10-3M (P <0.05). This response was significantly
      increased in the presence of L-NAME (P <0.001) and methylene blue (P <0.001),
      whereas H-89 inhibited the increase in coronary flow due to sodium hydrosulphide
      (P <0.001). Sodium hydrosulphide significantly decreased LVDP at all
      concentrations (P <0.001). In the presence of glibenclamide and H-89, the time
      period of the decrease in LVDP due to sodium hydrosulphide was extended (P
      <0.001), whereas methylene blue and L-NAME caused a significant reduction in the
      response to sodium hydrosulphide (P <0.05, P <0.01 respectively). CONCLUSION:
      Sodium hydrosulphide reduced heart rate and LVDP, and increased coronary flow in
      the isolated perfused rat heart; however, the mechanisms of action could not be
      fully elucidated.

PMID- 21969897
TI  - Trends and Characteristics of Head and Neck Injury from Falls: A hospital based
      study, Qatar.
AB  - OBJECTIVES: The aim of this retrospective descriptive hospital-based study was to
      determine the trend in the number, incidence and pattern of head and neck
      injuries involved with falls. METHODS: A retrospective analysis was carried out
      of 1,952 patients who were treated at the Accident and Emergency and Trauma
      centres of Hamad Medical Corporation, Qatar, for head (n = 1,629), neck (n = 225)
      and both (n = 98) injuries during the period 2001-2006. Head and neck injuries
      were determined according to the International Classification of Disease, ICD-10
      criteria. Details of all the trauma patients who were involved in falls were
      extracted from the database of the Emergency Medical Services (EMS), Hamad
      Medical Corporation. RESULTS: The majority of the victims were non-Qataris
      (78.6%), men (86.6%) and in the age group 20-29 years (26.8%). There was a
      disproportionately higher incidence of head and neck injuries from falls during
      weekends (27.1%). Nearly half of the head and neck injuries from falls occurred
      at work (49.4%). Neck injuries (10.2%) were more severe than head injuries
      (7.3%). The incidence rate of head and neck injuries per 10,000 population
      increased from 2.1 in the year 2001 to 5.5 in 2006, particularly among the
      elderly population above 60 years of age (13.1 in 2003 to 18.6 in the year 2006).
      Superficial injury to the head (29.4%) was more common among trauma patients.
      CONCLUSION: The present study findings revealed that the incidence of head and
      neck injuries was higher among young adults and the elderly population.

PMID- 21969898
TI  - The Disinfecting Potential of Contact Lens Soutions used by Sultan Qaboos
      University Students.
AB  - OBJECTIVES: This study aimed to determine the disinfecting potential of some
      contact lens solutions used by some university students in Oman. METHODS: This
      work was carried out from January to June 2010 in the Department of Microbiology
      & Immunology, College of Medicine and Health Sciences, Sultan Qaboos University,
      Oman. Fifty disinfecting solutions, in which contact lenses were disinfected
      according to the manufacturers' instructions, were collected from the students
      and plated on various microbiological culture media. Bacterial isolates were
      identified by API-20E, API-20NE and Phoenix automated systems while fungi were
      identified by their cultural characteristics and biochemistry. RESULTS: From 98
      isolates, Pseudomonas aeruginosa was 23.5%; Penicillium, 13%; Candida species,
      9.2%; coagulase negative staphylococci, 9.2%; Serratia marcescens, 6.1%;
      Bacillus, 5.1%; Aspergillus flavus, 5.1%; Serratia liquefaciens, Pseudomonas
      fluorescens, Enterobacter cloacae and Aspergillus niger, 4.1% each; Chryseomonas
      luteola and Chryseomonas indologenes, 3.1% each; Stenotrophomonas maltophilia,
      Serratia odorifera, 2.0% each; Enterobacter aerogenes and Klebsiella pneumoniae,
      1% each. Most isolates (65%) came from polyhexanide containing solutions.
      CONCLUSION: Contact lens disinfecting solutions with the same formulations, but
      manufactured by different companies, possessed different disinfecting potentials.

PMID- 21969899
TI  - Myelomatous Pleural Effusion: Case report and review of the literature.
AB  - Plasma cell myeloma is an uncommon disease which, besides primarily involving the
      bone marrow, has a tendency to involve other organs thus presenting with
      different clinical manifestations. While pleural effusions are infrequent in this
      disease, true myelomatous pleural effusions are extremely rare. We report the
      case of a middle-aged Omani man with relapsed plasma cell myeloma who developed
      bilateral pleural effusions. The diagnosis of myelomatous pleural effusion was
      made by finding many abnormal plasma cells as well as a high level of a
      monoclonal protein (IgG kappa) in the pleural fluid. In spite of a good initial
      response to therapy, the patient had progressive disease and died 6 months later
      with bacterial sepsis. We present a review of the literature that indicates the
      rarity of such a manifestation and its association with poor prognosis and short
      survival.

PMID- 21969900
TI  - Dengue Haemorrhagic Fever presenting as Acute Abdomen.
AB  - We describe a case of a 38 year-old Sri Lankan female who was referred to the
      surgeon on call with a picture of acute abdomen. She presented with a three-day
      history of fever, headache, abdominal pain and diarrhoea; however, the physical
      examination was not consistent with acute abdomen. Her platelet count was 22
      *10(9)/L. A diagnosis of dengue haemorrhagic fever (DHF) was made and dengue
      serology was positive. Dengue epidemics have been associated with a variety of
      gastrointestinal symptoms and signs, including acute abdomen. Acute abdomen in
      patients with DHF makes the diagnosis and management challenging.

PMID- 21969901
TI  - Visceral Leishmaniasis with an Unusual Presentation in an HIV Positive Patient.
AB  - Visceral leishmaniasis is a disease caused by a haemoflagellate protozoan of the
      genus Leishmania. It has a wide geographical spread. Classic cases are found
      primarily in children and present with typical features that include fever,
      anaemia, hepatosplenomegaly, hypergammaglobulinaemia, and pancytopenia. The
      diagnosis is usually achieved by bone marrow smears, culture and serology;
      however, it can manifest itself atypically, mostly in patients infected with HIV
      and geriatric immunocompetent patients. We report an unusual case of visceral
      leishmaniasis diagnosed in a 27 year-old HIV-infected male who presented with
      abdominal discomfort and diarrhoea of four weeks duration associated with nausea
      and vomiting, but with no typical symptoms or signs of visceral leishmaniasis.
      The diagnosis was established through the identification of the Leishmania
      organism in duodenal and colonic biopsies and confirmed by subsequent bone marrow
      smears.

PMID- 21969902
TI  - Lip necrosis as a complication of a prone position in scoliosis surgery.
AB  - During the prone positioning of patients for scoliosis surgery, bony prominences
      should be protected to avoid pressure necrosis and the face should be carefully
      positioned to protect the eyes and ears, etc. The author reports a lower lip
      necrosis in a 16 year-old female as a complication of improper prone positioning
      during scoliosis surgery. The condition was treated successfully with an
      advancement flap.

PMID- 21969903
TI  - Reconstruction of Exenterated Orbit using Combined Surgical and Prosthetic
      Approach.
AB  - Reconstruction of an exenterated orbit remains a challenge. Orbital prostheses
      are nowadays are made of silicone elastomers. A major limitation with silicone
      orbital prostheses is their relatively short life span. This case report
      describes the treatment of a patient with an exenterated orbit using a combined
      surgical and prosthetic approach. The upper and lower eyelids were reconstructed
      surgically using a deltopectoral flap. A sectional eye prosthesis was made and
      placed in the modified bottle-neck shaped defect to restore the patient's
      appearance and confidence.

PMID- 21969904
TI  - Acquired Pure Red Cell Aplasia caused by Parvovirus B19 Infection following a
      Renal Transplant.
AB  - We report a young Omani male who developed severe and persistent anaemia after a
      kidney transplantation while being on immunosuppression therapy, standard
      practice to prevent rejection of the transplanted kidney. His bone marrow
      aspirate showed the classic morphological changes of pure red cell aplasia
      (PRCA), induced by parvovirus B19 infection which is the presence of giant
      proerythroblasts with viral inclusions. The virus was also demonstrated by
      polymerase chain reaction in the blood along with IgM antibodies to parvovirus
      B19. He responded dramatically to high dose immunoglobulin with a normalisation
      of his haemoglobin level in two weeks and remained normal until seven months
      later. Parvovirus B19 induced PRCA can be cured. This aetiology must be kept in
      mind especially when a chronic anaemia, refractory to treatment, is accompanied
      by a reticulocytopenia. The latter reflects the lysis of the proerythroblasts,
      preventing maturation of the erythroid cells causing anaemia. Early recognition
      and prompt treatment spares the patient unnecessary exposure to blood
      transfusions, erythropoietin and renal disease caused by the virus. PRCA
      secondary to parvovirus B19 infection following kidney transplantation is
      reported in the literature, but not in the Omani population. To the best of our
      knowledge, this is the first such report in Oman.

PMID- 21969905
TI  - CADASIL - Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and
      Leukoencephalopathy.

PMID- 21969906
TI  - Late Corneal Thinning and Keratitis following Mitomycin-C use in Pterygium
      Surgery.

PMID- 21969907
TI  - Re: UN Millennium Development Goals and Oman: Kudos to Oman on its 40 National
      Day.

PMID- 21969908
TI  - Re: Radiation Exposure from Medical Imaging: A Wake-up Call for Oman!

PMID- 21969909
TI  - Engraftment of insulin-producing cells from porcine islets in non-immune
      suppressed rats or nonhuman primates transplanted previously with embryonic pig
      pancreas.
AB  - Transplantation therapy for diabetes is limited by unavailability of donor organs
      and outcomes complicated by immunosuppressive drug toxicity. Xenotransplantation
      is a strategy to overcome supply problems. Implantation of tissue obtained early
      during embryogenesis is a way to reduce transplant immunogenicity. Insulin
      producing cells originating from embryonic pig pancreas obtained very early
      following pancreatic primordium formation (embryonic day 28 (E28)) engraft long
      term in non-immune, suppressed diabetic rats or rhesus macaques. Morphologically,
      similar cells originating from adult porcine islets of Langerhans (islets)
      engraft in non-immune-suppressed rats or rhesus macaques previously transplanted
      with E28 pig pancreatic primordia. Our data are consistent with induction of
      tolerance to an endocrine cell component of porcine islets induced by previous
      transplantation of embryonic pig pancreas, a novel finding we designate
      organogenetic tolerance. The potential exists for its use to enable the use of
      pigs as islet cell donors for humans with no immune suppression requirement.

PMID- 21969910
TI  - High-resolution optical coherence tomography retinal imaging: a case series
      illustrating potential and limitations.
AB  - Purpose. To present a series of retinal disease cases that were imaged by
      spectral domain optical coherence tomography (SD-OCT) in order to illustrate the
      potential and limitations of this new imaging modality. Methods. The series
      comprised four selected cases (one case each) of age-related macular degeneration
      (ARMD), diabetic retinopathy (DR), central retinal artery occlusion (CRAO), and
      branch retinal vein occlusion (BRVO). Patients were imaged using the Heidelberg
      Spectralis (Heidelberg Engineering, Germany) in SD-OCT mode. Patients also
      underwent digital fundus photography and clinical assessment. Results. SD-OCT
      imaging of a case of age-related macular degeneration revealed a subfoveal
      choroidal neovascular membrane with detachment of the retinal pigment epithelium
      (RPE) and neurosensory retina. Using SD-OCT, the cases of DR and BRVO both
      exhibited macular edema with cystoid spaces visible in the outer retina.
      Conclusions. The ability of SD-OCT to clearly and objectively elucidate subtle
      morphological changes within the retinal layers provides information that can be
      used to formulate diagnoses with greater confidence.

PMID- 21969911
TI  - Lambert-eaton myasthenic syndrome; pathogenesis, diagnosis, and therapy.
AB  - Lambert-Eaton Myasthenic Syndrome (LEMS) is a rare disease with a well
      characterized pathogenesis. In 50% of the patients, LEMS is a paraneoplastic
      manifestation and caused by a small cell lung carcinoma (SCLC). Both LEMS
      patients with SCLC and those without this tumour have in 85% of cases
      pathogenetic antibodies of very high LEMS specificity against voltage-gated
      calcium channels (VGCCs) in the cell membrane of the presynaptic motor nerve
      terminal. Better understanding of LEMS pathogenesis has lead to targeted
      symptomatic therapy aimed at the neuromuscular junction and to semispecific
      immuno-suppression. For SCLC LEMS, tumour therapy is essential.

PMID- 21969912
TI  - Administration of harmine and imipramine alters creatine kinase and mitochondrial
      respiratory chain activities in the rat brain.
AB  - The present study evaluated mitochondrial respiratory chain and creatine kinase
      activities after administration of harmine (5, 10, and 15 mg/kg) and imipramine
      (10, 20, and 30 mg/kg) in rat brain. After acute treatment occurred an increase
      of creatine kinase in the prefrontal with imipramine (20 and 30 mg/kg) and
      harmine in all doses, in the striatum with imipramine (20 and 30 mg/kg) and
      harmine (5 and 10 mg/kg); harmine (15 mg/kg) decreased creatine kinase. In the
      chronic treatment occurred an increase of creatine kinase with imipramine (20
      mg/kg), harmine (5 mg/kg) in the prefrontal with imipramine (20 and 30 mg/kg) and
      harmine (5 and 10 mg/kg) in the striatum. In the acute treatment, the complex I
      increased in the prefrontal with harmine (15 mg/kg) and in the striatum with
      harmine (10 mg/kg); the complex II decreased with imipramine (20 and 30 mg/kg) in
      the striatum; the complex IV increased with imipramine (30 mg/kg) in the
      striatum. In the chronic treatment, the complex I increased with harmine (5
      mg/kg) in the prefrontal; the complex II increased with imipramine (20 mg/kg) in
      the prefrontal; the complex IV increased with harmine (5 mg/kg) in the striatum.
      Finally, these findings further support the hypothesis that harmine and
      imipramine could be involved in mitochondrial function.

PMID- 21969913
TI  - Previous renal replacement therapy time at start of peritoneal dialysis
      independently impact on peritoneal membrane ultrafiltration failure.
AB  - Background. Peritoneal membrane changes are induced by uraemia per se. We
      hypothesise that previous renal replacement therapy (RRT) time and residual renal
      function (RRF) at start of peritoneal dialysis impact on ultrafiltration failure
      (UFF). Methods. The time course of PET parameters from 123 incident patients,
      followed for median 26 (4-105) months, was evaluated by mixed linear model.
      Glucose 3.86% solutions were not used in their standard therapy. Sex, age,
      diabetes, previous RRT time, RRF, comorbidity score, PD modality and peritonitis
      episodes were investigated as possible determinants of UFF-free survival.
      Results. PET parameters remained stable during follow up. CA125 decreased
      significantly. Inherent UFF was diagnosed in 8 patients, 5 spontaneously
      recovering. Acquired UFF group presented type I UFF profile with compromised
      sodium sieving. At baseline they had lower RRF and longer previous time of RRT
      which remained significantly associated with UFF-free survival by Cox
      multivariate analysis (HR 0.648 (0.428-0.980), P = 0.04) and (HR 1.016 (1.004
      1.028), P = 0.009, resp.). UFF free survival was 97%, 87% and 83% at 1, 3 and 5
      years, respectively. Conclusions. Inherent UFF is often unpredictable but
      transitory. On the other hand baseline lower RRF and previous RRT time
      independently impact on ultrafiltration failure free survival. In spite of these
      detrimental factors generally stable long-term peritoneal transport parameters is
      achievable with a 5-year cumulative UFF free survival of 83%. This study adds a
      further argument for a PD-first policy.

PMID- 21969914
TI  - A novel mouse model of Alzheimer's disease with chronic estrogen deficiency leads
      to glial cell activation and hypertrophy.
AB  - The role of estrogens in Alzheimer's disease (AD) involving beta-amyloid (Abeta)
      generation and plaque formation was mostly tested in ovariectomized mice with or
      without APP mutations. The aim of the present study was to explore the
      abnormalities of neural cells in a novel mouse model of AD with chronic estrogen
      deficiency. These chimeric mice exhibit a total FSH-R knockout (FORKO) and carry
      two transgenes, one expressing the beta-amyloid precursor protein (APPsw, Swedish
      mutation) and the other expressing presenilin-1 lacking exon 9 (PS1Delta9). The
      most prominent changes in the cerebral cortex and hippocampus of these
      hypoestrogenic mice were marked hypertrophy of both cortical neurons and
      astrocytes and an increased number of activated microglia. There were no
      significant differences in the number of Abeta plaques although they appeared
      less compacted and larger than those in APPsw/PS1Delta9 control mice. Similar
      glia abnormalities were obtained in wild-type primary cortical neural cultures
      treated with letrozole, an aromatase inhibitor. The concordance of results from
      APPsw/PS1Delta9 mice with or without FSH-R deletion and those with letrozole
      treatment in vitro (with and without Abeta treatment) of primary
      cortical/hippocampal cultures suggests the usefulness of these models to explore
      molecular mechanisms involved in microglia and astrocyte activation in
      hypoestrogenic states in the central nervous system.

PMID- 21969915
TI  - Comparison of Vascular Perturbations in an Abeta-Injected Animal Model and in AD
      Brain.
AB  - The validity of amyloid-beta peptide (Abeta(1-42)) intrahippocampal injection, as
      an animal model of Alzheimer's disease (AD), has previously been considered in
      terms of inflammatory reactivity and neuronal damage. In this work, we have
      extended the testing of the animal model to vasculature by comparison of selected
      properties of microvessels in vivo with those in human AD brain tissue. The
      injection of Abeta(1-42), relative to control PBS (phosphate buffered saline),
      increased the mean number of microvessels and diminished the mean length of
      microvessels in the molecular layer of dentate gyrus. The animal model showed
      Abeta(1-42), but not PBS, injection was associated with abnormalities in
      morphology of microvessels which were characterized as looping, fragmented, knob
      like, uneven, and constricted. In particular, numbers of constricted
      microvessels, defined as vessels with diameters less than 3 MUm, were
      considerably enhanced for Abeta(1-42), compared to PBS, injection. In comparison,
      human AD brain demonstrated an elevated number of microvessels with a diminished
      mean length relative to nondemented (ND) brain. Additionally, microvessel
      perturbations in AD brain showed a similar pattern of morphological abnormalities
      to those observed in Abeta(1-42)-injected rat hippocampus. Constricted
      microvessels were a prominent feature of AD brain but were rarely observed in ND
      tissue. These results provide the first evidence that a peptide-injection animal
      model exhibits a commonality in perturbations of microvessels compared with those
      evident in AD brain.

PMID- 21969916
TI  - Assessment of prosodic communicative efficiency in Parkinson's disease as judged
      by professional listeners.
AB  - This study examines the impact of Parkinson's disease (PD) on communicative
      efficiency conveyed through prosody. A new assessment method for evaluating
      productive prosodic skills in Dutch speaking dysarthric patients was devised and
      tested on 36 individuals (18 controls, 18 PD patients). Three professional
      listeners judged the intended meanings in four communicative functions of Dutch
      prosody: Boundary Marking, Focus, Sentence Typing, and Emotional Prosody. Each
      function was tested through reading and imitation. Interrater agreement was
      calculated. Results indicated that healthy speakers, compared to PD patients,
      performed significantly better on imitation of Boundary Marking, Focus, and
      Sentence Typing. PD patients with a moderate or severe dysarthria performed
      significantly worse on imitation of Focus than on reading of Focus. No
      significant differences were found for Emotional Prosody. Judges agreed well on
      all tasks except Emotional Prosody. Future research will focus on elaborating the
      assessment and on developing a therapy programme paralleling the assessment.

PMID- 21969918
TI  - Spot-on skin lipid complex as an adjunct therapy in dogs with atopic dermatitis:
      an open pilot study.
AB  - The purpose of this paper was to evaluate the efficacy of topical skin lipid
      complex (SLC) in canine atopic dermatitis (AD). Eight dogs with chronic AD and no
      improvement of main therapy in symptoms, erythema, lichenification, excoriation,
      and alopecia in the previous month were treated with SLC topically as adjunct
      therapy at lesion sites twice weekly for 12 weeks. A statistically significant
      reduction (26.0%, P < 0.05) in the third version of the Canine Atopic Dermatitis
      Extent and Severity Index (CADESI-03) modification from baseline was recorded 6
      weeks after treatment, with marked reduction in the erythema subscore (36.2%, P <
      0.005). A significant reduction in excoriation and alopecia subscores was
      observed 6 weeks after treatment (39.9%, P < 0.05 and 19.9%, P < 0.05, resp.).
      However, the lichenification subscore was not reduced significantly at 6 or 12
      weeks. These findings suggest that topical SLC may have therapeutic and clinical
      benefits in dogs with AD.

PMID- 21969917
TI  - A perfusion MRI study of emotional valence and arousal in Parkinson's disease.
AB  - Background. Brain regions subserving emotion have mostly been studied using
      functional magnetic resonance imaging (fMRI) during emotion provocation
      procedures in healthy participants. Objective. To identify neuroanatomical
      regions associated with spontaneous changes in emotional state over time.
      Methods. Self-rated emotional valence and arousal scores, and regional cerebral
      blood flow (rCBF) measured by perfusion MRI, were measured 4 or 8 times spanning
      at least 2 weeks in each of 21 subjects with Parkinson's disease (PD). A random
      effects SPM analysis, corrected for multiple comparisons, identified significant
      clusters of contiguous voxels in which rCBF varied with valence or arousal.
      Results. Emotional valence correlated positively with rCBF in several brain
      regions, including medial globus pallidus, orbital prefrontal cortex (PFC), and
      white matter near putamen, thalamus, insula, and medial PFC. Valence correlated
      negatively with rCBF in striatum, subgenual cingulate cortex, ventrolateral PFC,
      and precuneus-posterior cingulate cortex (PCC). Arousal correlated positively
      with rCBF in clusters including claustrum-thalamus-ventral striatum and inferior
      parietal lobule and correlated negatively in clusters including posterior insula
      mediodorsal thalamus and midbrain. Conclusion. This study demonstrates that the
      temporal stability of perfusion MRI allows within-subject investigations of
      spontaneous fluctuations in mental state, such as mood, over relatively long-time
      intervals.

PMID- 21969919
TI  - The accuracy of dynamic predictive autofocusing for whole slide imaging.
AB  - CONTEXT: Whole slide imaging (WSI) for digital pathology involves the rapid
      automated acquisition of multiple high-power fields from a microscope slide
      containing a tissue specimen. Capturing each field in the correct focal plane is
      essential to create high-quality digital images. Others have described a novel
      focusing method which reduces the number of focal planes required to generate
      accurate focus. However, this method was not applied dynamically in an automated
      WSI system under continuous motion. AIMS: This report measures the accuracy of
      this method when applied in a rapid continuous scan mode using a dual sensor WSI
      system with interleaved acquisition of images. METHODS: We acquired over 400
      tiles in a "stop and go" scan mode, surveying the entire z depth in each tile and
      used this as ground truth. We compared this ground truth focal height to the
      focal height determined using a rapid 3-point focus algorithm applied dynamically
      in a continuous scanning mode. RESULTS: Our data showed the average focal height
      error of 0.30 (+/-0.27) MUm compared to ground truth, which is well within the
      system's depth of field. On a tile by tile assessment, approximately 95% of the
      tiles were within the system's depth of field. Further, this method was six times
      faster than acquiring tiles compared to the same method in a non-continuous scan
      mode. CONCLUSIONS: The data indicates that the method employed can yield a
      significant improvement in scan speed while maintaining highly accurate
      autofocusing.

PMID- 21969921
TI  - Using XML to encode TMA DES metadata.
AB  - BACKGROUND: The Tissue Microarray Data Exchange Specification (TMA DES) is an XML
      specification for encoding TMA experiment data. While TMA DES data is encoded in
      XML, the files that describe its syntax, structure, and semantics are not. The
      DTD format is used to describe the syntax and structure of TMA DES, and the ISO
      11179 format is used to define the semantics of TMA DES. However, XML Schema can
      be used in place of DTDs, and another XML encoded format, RDF, can be used in
      place of ISO 11179. Encoding all TMA DES data and metadata in XML would simplify
      the development and usage of programs which validate and parse TMA DES data. XML
      Schema has advantages over DTDs such as support for data types, and a more
      powerful means of specifying constraints on data values. An advantage of RDF
      encoded in XML over ISO 11179 is that XML defines rules for encoding data,
      whereas ISO 11179 does not. MATERIALS AND METHODS: We created an XML Schema
      version of the TMA DES DTD. We wrote a program that converted ISO 11179
      definitions to RDF encoded in XML, and used it to convert the TMA DES ISO 11179
      definitions to RDF. RESULTS: We validated a sample TMA DES XML file that was
      supplied with the publication that originally specified TMA DES using our XML
      Schema. We successfully validated the RDF produced by our ISO 11179 converter
      with the W3C RDF validation service. CONCLUSIONS: All TMA DES data could be
      encoded using XML, which simplifies its processing. XML Schema allows datatypes
      and valid value ranges to be specified for CDEs, which enables a wider range of
      error checking to be performed using XML Schemas than could be performed using
      DTDs.

PMID- 21969920
TI  - Implementation of whole slide imaging in surgical pathology: A value added
      approach.
AB  - BACKGROUND: Whole slide imaging (WSI) makes it possible to capture images of an
      entire histological slide. WSI has established roles in surgical pathology,
      including support of off-site frozen section interpretation, primary diagnosis,
      educational activities, and laboratory quality assurance (QA) activities.
      Analyses of the cost of WSI have traditionally been based solely on direct costs
      and diagnostic accuracy; however, these types of analyses largely ignore workflow
      and cost issues that arise as a result of redundancy, the need for additional
      staffing, and customized software development when WSI is integrated into routine
      diagnostic surgical pathology. The pre-scan, scan, and post-scan costs; quality
      control and QA costs; and IT process costs can be significant, and consequently,
      pathology groups can find it difficult to perform a realistic cost-benefit
      analysis of adding WSI to their practice. MATERIALS AND METHODS: In this paper,
      we report a "value added" approach developed to guide our decisions regarding
      integration of WSI into surgical pathology practice. The approach focuses on
      specific operational measures (cost, time, and enhanced patient care) and
      practice settings (clinical, education, and research) to identify routine
      activities in which the addition of WSI can provide improvements. RESULTS: When
      applied to our academic pathology group practice, the value added approach
      resulted in expanded and improved operations, as demonstrated by outcome based
      measures. CONCLUSION: A value added can be used to perform a realistic cost
      benefit analysis of integrating WSI into routine surgical pathology practice.

PMID- 21969922
TI  - Use of mobile high-resolution device for remote frozen section evaluation of
      whole slide images.
AB  - INTRODUCTION: With recent advances, it is now possible to view whole slide images
      (WSI) on mobile, high-resolution, viewing devices (MVD). This creates a new
      paradigm in which MVDs may be used for consultation and/or diagnosis. Validation
      of the results with devices is important for practitioners and regulators. We
      evaluated the use of MVDs in frozen section (FS) interpretation. METHODS: A
      series of 72 consecutive FS cases were selected for potential inclusion in the
      study. A 67 case subset of these were successfully scanned at 20x magnification.
      Scan times were recorded. A sample of WSI FS cases, with gross and clinical
      information, was presented to six pathologists on an iPad MVD using the Interpath
      application. Times to diagnosis were recorded. Results were compared with the
      original reported and final diagnosis. Participants also completed a survey
      assessing image quality, interface, and diagnostic comfort level. RESULTS: Scan
      times averaged two minutes and 46 seconds per slide, (standard deviation [SD] 2
      minutes 46 seconds). Evaluation times averaged 4 minutes and 59 seconds per case,
      range to 13 minutes and 50 seconds, SD 3 minutes 48 seconds. Concordance between
      initial FS diagnosis and rendered through the MVD was 89%. Minor discrepancies
      made up 8% and major disagreements 3%. The kappa statistic for this series is
      0.85. Participants rated the experience at 5 on a 10-point scale, range 3 to 7.
      Two-thirds found the image quality to be adequate, half were satisfied with image
      resolution, and 33% would be willing to make a diagnosis on the iPad, plus one
      only for special cases. Five of six respondents (83%) found the navigation with
      the study software difficult. CONCLUSION: Image fidelity and resolution makes the
      iPad potentially suitable for WSI evaluation of FS. Acceptable accuracy is
      attainable for FS interpretation. But, although possible to obtain acceptable
      results, use of the iPad with Interpath to view WSI is not easy and meets user
      resistance. The obstacle of slide navigation at high magnification could
      introduce frustrations, delays, or errors.

PMID- 21969923
TI  - Use of a laboratory information system driven tool for pre-signout quality
      assurance of random cytopathology reports.
AB  - BACKGROUND: Quality assurance (QA) programs in cytopathology laboratories in the
      USA currently primarily involve the review of Pap tests per clinical laboratory
      improvement amendments of 1988 federal regulations. A pre-signout quality
      assurance tool (PQAT) at our institution allows the laboratory information system
      (LIS) to also automatically and randomly select an adjustable percentage of non
      gynecological cytopathology cases for review before release of the final report.
      The aim of this study was to review our experience and the effectiveness of this
      novel PQAT tool in cytology. MATERIALS AND METHODS: Software modifications in the
      existing LIS application (CoPathPlus, Cerner) allow for the random QA of 8% of
      cases prior to signout. Selected cases are assigned to a second QA
      cytopathologist for review and all agreement and disagreements tracked. Detected
      errors are rectified before the case is signed out. Data from cases selected for
      PQAT over an 18-month period were collected and analyzed. RESULTS: The total
      number of non-gynecological cases selected for QA review was 1339 (7.45%) out of
      17,967 cases signed out during this time period. Most (1304) cases (97.4%) had an
      agreement in diagnosis. In 2.6% of cases, there were disagreements, including 34
      minor and only 1 major disagreement. Average turnaround time of cases selected
      for review was not significantly altered. CONCLUSION: The PQAT provides a
      prospective QA mechanism in non-gynecological cytopathology to prevent diagnostic
      errors from occurring. This LIS-driven tool allows for peer review and corrective
      action to be taken prior to reporting without delaying turnaround time, thereby
      improving patient safety.

PMID- 21969924
TI  - International relationships worth pursuing.

PMID- 21969925
TI  - Cystic echinococcosis: late rupture and complication of a stable pulmonary cyst.
AB  - Cystic echinococcosis is observed worldwide. Traditional management includes an
      invasive surgical approach with adjunctive chemotherapy. It has been suggested
      that observation alone may be appropriate in asymptomatic individuals with stable
      cysts. A case involving a 38-year-old Peruvian man with an asymptomatic
      bronchogenic cyst (suspected to be due to echinococcus, but never definitely
      diagnosed) is presented. The cyst was first noted in 1998, and was followed for
      10 years during which time he remained asymptomatic with minimal radiographic
      change. One year later, in 2009, he presented with acute rupture of the cyst
      causing empyema. The patient required thoracotomy, decortication and resection of
      the ruptured cyst. Final pathology showed Echinococcus organisms. The patient
      responded well to treatment with albendazole and praziquantel, and became
      completely asymptomatic within six months. The present case demonstrates that
      echinococcal cysts may be at risk of spontaneous rupture, even after many years
      of clinical stability, thus supporting the case for resection of asymptomatic
      cysts suspected of being echinococcal at the time of diagnosis. In addition, the
      case illustrates that medical therapy with albendazole and praziquantel, in
      conjunction with surgical drainage, can be successful in the treatment of
      echinococcal empyema.

PMID- 21969926
TI  - A case of adalimumab-induced pneumonitis in a 45-year-old man with Crohn's
      disease.
AB  - Adalimumab is a human monoclonal antibody against tumour necrosis factor-alpha
      that has been associated with acute lung toxicity, mainly in patients with
      rheumatoid arthritis. Descriptions of similar patterns of lung injury in patients
      treated with adalimumab for inflammatory bowel disease are emerging in the
      literature. A case involving a 45-year-old man with Crohn's disease who developed
      a nonbronchiolitis inflammatory nodular pattern of lung injury after starting
      adalimumab is reported.

PMID- 21969927
TI  - Long-term impact of bronchopulmonary dysplasia on pulmonary function.
AB  - BACKGROUND: Bronchopulmonary dysplasia (BPD) and the longterm respiratory
      consequences of prematurity are unfamiliar to adult respirologists and remain
      under-recognized entities to adult caregivers. In Canada, the incidence of
      preterm births and its main chronic respiratory complication, BPD, have increased
      over the past 25 years. OBJECTIVE: To describe the posthospitalization morbidity,
      medication use, health care use and pulmonary function tests of a large cohort of
      individuals with preterm birth complicated by BPD. METHODS: A retrospective
      review of the hospital records of 322 preterm infants with BPD was conducted.
      Outcome variables were compared across levels of disease severity. Differences
      between groups were tested with one-way ANOVA for continuous variables and the
      Mantel-Haenszel chi-squared test for ordinal variables. RESULTS: Outcomes after
      the initial hospitalization that were associated with the initial severity of BPD
      were as follows: hospital readmissions in the first two years of life, the
      presence of developmental delay, forced expiratory volume in 1 s and forced vital
      capacity on pulmonary function tests in patients between eight and 15 years of
      age. CONCLUSION: Initial BPD severity was an important predictor of pulmonary
      function abnormality and health care use during childhood.

PMID- 21969929
TI  - Feasibility of a provincial voluntary reporting system for work-related asthma in
      Ontario.
AB  - OBJECTIVE: The Ontario Work-Related Asthma Surveillance System: Physician
      Reporting (OWRAS) Network was established in 2007 to estimate the prevalence of
      work-related asthma (WRA) in Ontario, and to test the feasibility of collecting
      data for cases of WRA from physicians voluntarily. METHODS: More than 300
      respirologists, occupational medicine physicians, allergists and primary care
      providers in Ontario were invited to participate in monthly reporting of WRA
      cases by telephone, postal service or e-mail. RESULTS: Since 2007, 49 physicians
      have registered with the OWRAS Network and, to date, have reported 34 cases of
      occupational asthma and 49 cases of work-exacerbated asthma. Highly reactive
      chemicals were the most frequently reported suspected causative agent of the 108
      suspected exposures reported. CONCLUSION: Despite the challenge of enlisting a
      representative sample of physicians in Ontario willing to report, the OWRAS
      Network has shown that it is feasible to implement a voluntary reporting system
      for WRA; however, its long-term sustainability is currently unknown.

PMID- 21969928
TI  - Comparison of polysomnographic and portable home monitoring assessments of
      obstructive sleep apnea in Saskatchewan women.
AB  - OBJECTIVES: To compare a commercially available, level III in-home diagnostic
      sleep test (Embletta, Embletta USA) and in-laboratory polysomnography (PSG) in
      women with suspected obstructive sleep apnea (OSA). METHODS: Consecutive women
      scheduled for routine PSG testing for evaluation of clinically suspected OSA and
      who met inclusion/exclusion criteria, were invited to participate. An in-home
      Embletta portable monitor test was performed one week before or after diagnostic
      PSG. RESULTS: Forty-seven of 96 women who met the inclusion/exclusion criteria
      agreed to participate. The mean (+/- SD) age of the patients was 52.0 +/- 11.0
      years, with a mean body mass index of 34.86 +/- 9.04 kg/m2, and 66% (31 of 47) of
      patients were at high risk for OSA according to the Berlin score. Paired analysis
      of the overall population revealed no significant difference in mean
      apnea/hypopnea index (AHI) between the two diagnostic methods (P = 0.475). At an
      AHI of >= 5, the Embletta test was highly sensitive (90.6%) in determining
      abnormal versus normal OSA, with a positive predictive value of 82.7%. However, a
      higher Embletta AHI threshold of >= 10 may be more useful, with a higher level of
      agreement (kappa coefficient) with PSG testing and a positive predictive value of
      92.3%. The in-home study was less useful at distinguishing severe from nonsevere
      OSA, yielding a sensitivity of 50%. CONCLUSIONS: In women believed to be at high
      risk for OSA, Embletta in-home sleep testing is useful for the detection of sleep
      disordered breathing.

PMID- 21969930
TI  - Effects of a short course of inhaled corticosteroids in noneosinophilic asthmatic
      subjects.
AB  - BACKGROUND: Noneosinophilic asthma has been regarded as a distinct phenotype
      characterized by a poor response to inhaled corticosteroids (ICS). OBJECTIVE: To
      determine whether noneosinophilic, steroid-naive asthmatic subjects show an
      improvement in asthma control, asthma symptoms and spirometry after four weeks of
      treatment with ICS, and whether they further benefit from the addition of a long
      acting beta-2 agonists to ICS. METHODS: A randomized, double-blind, placebo
      controlled, multicentre study comparing the efficacy of placebo versus inhaled
      fluticasone propionate 250 mcg twice daily for four weeks in mildly uncontrolled,
      steroid-naive asthmatic subjects with a sputum eosinophil count of 2% or less.
      This was followed by an open-label, four-week treatment period with fluticasone
      propionate 250 mcg/salmeterol 50 mcg, twice daily for all subjects. RESULTS:
      After four weeks of double-blind treatment, there was a statistically significant
      and clinically relevant improvement in the mean (+/- SD) Asthma Control
      Questionnaire score in the ICS-treated group (n = 6) (decrease of 1.0 +/- 0.5)
      compared with the placebo group (n = 6) (decrease of 0.09 +/- 0.4) (P = 0.008).
      Forced expiratory volume in 1 s declined in the placebo group (-0.2 +/- 0.2 L)
      and did not change in the ICS group (0.04 +/- 0.1 L) after four weeks of
      treatment (P = 0.02). The open-label treatment with fluticasone propionate 250
      mcg/salmeterol 50 mcg did not produce additional improvements in those who were
      previously treated for four weeks with inhaled fluticasone alone. CONCLUSION: A
      clinically important and statistically significant response to ICS was observed
      in mildly uncontrolled noneosinophilic asthmatic subjects.

PMID- 21969931
TI  - Health-related quality of life and 6 min walk distance in patients with
      idiopathic pulmonary fibrosis.
AB  - BACKGROUND: Few studies have investigated the relationship between physiological
      outcomes and quality of life in patients with idiopathic pulmonary fibrosis
      (IPF). Health-related quality of life (HRQL) data may provide a valuable patient
      centred outcome for the evaluation of interventions. Determination of which
      physiological and functional variables are associated with HRQL may facilitate
      interpretation of disease progression and impacts of therapy. OBJECTIVES: To
      determine whether an association between Medical Outcomes Short-Form 36 and St
      George's Respiratory Questionnaire scores and other markers of disease severity
      exist, and to identify which physiological and functional variables are
      independently associated with HRQL. METHODS: In a cross-sectional study, 137
      patients with IPF completed HRQL surveys and underwent clinical assessment.
      Multiple linear regression analysis was used to determine the relationship
      between age, forced vital capacity, diffusing capacity of carbon monoxide, 6 min
      walk distance (6MWD) and oxygen requirement, and HRQL scores. RESULTS: 6MWD was
      the only functional measure of disease severity significantly associated with all
      domain scores of the St George's Respiratory Questionnaire and the Medical
      Outcomes Short-Form 36 physical component summary score. CONCLUSIONS: 6MWD was
      associated with HRQL among patients with IPF. This highlights the importance of
      6MWD not only as a prognostic indicator in IPF, but also a predictor of HRQL and
      a meaningful outcome for patients.

PMID- 21969933
TI  - Whipple's disease-associated pulmonary hypertension with positive vasodilator
      response despite severe hemodynamic derangements.
AB  - Pulmonary hypertension (PH) associated with Whipple's disease (WD-PH) is
      extremely rare, and the underlying pathophysiological processes are incompletely
      understood. Alterations in hemodynamics can be severe, with right ventricular
      (RV) dysfunction being common. A case involving a 23-year-old man with WD-PH who
      exhibited a dramatic vasodilator response during right heart catheterization
      despite severely altered pulmonary hemodynamics and concomitant RV dysfunction is
      reported. While the patient's symptoms responded poorly to treatment with
      nifedipine and sildenafil, significant improvement in dyspnea, RV dysfunction and
      pulmonary pressures were noted following antibiotic therapy. The present report
      highlights that despite severely elevated pulmonary artery pressures and RV
      dysfunction in WD-PH patients, a highly significant vasodilator response and
      dramatic improvement with antibiotic therapy may be observed. Furthermore, the
      case highlights the phenomenon of PH in the setting of inflammation, suggesting
      that adequate control of the inflammatory response can be accompanied by a marked
      improvement in hemodynamics in certain types of PH.

PMID- 21969934
TI  - Normal expiratory flow rate and lung volumes in patients with combined emphysema
      and interstitial lung disease: a case series and literature review.
AB  - Pulmonary function tests in patients with idiopathic pulmonary fibrosis
      characteristically show a restrictive pattern including small lung volumes and
      increased expiratory flow rates resulting from a reduction in pulmonary
      compliance due to diffuse fibrosis. Conversely, an obstructive pattern with
      hyperinflation results in emphysema by loss of elastic recoil, expiratory
      collapse of the peripheral airways and air trapping. When the diseases coexist,
      pulmonary volumes are compensated, and a smaller than expected reduction or even
      normal lung volumes can be found. The present report describes 10 patients with
      progressive breathlessness, three of whom experienced severe limitation in their
      quality of life. All patients showed lung interstitial involvement and emphysema
      on computed tomography scan of the chest. The 10 patients showed normal
      spirometry and lung volumes with severe compromise of gas exchange. Normal lung
      volumes do not exclude diagnosis of idiopathic pulmonary fibrosis in patients
      with concomitant emphysema. The relatively preserved lung volumes may
      underestimate the severity of idiopathic pulmonary fibrosis and attenuate its
      effects on lung function parameters.

PMID- 21969935
TI  - Can a self-management education program for patients with chronic obstructive
      pulmonary disease improve quality of life?
AB  - OBJECTIVE: To assess the effects of a self-management program on health-related
      quality of life (HRQoL) and morbidity commonly associated with chronic
      obstructive pulmonary disease (COPD). METHODS: A total of 57 outpatients with
      stable COPD received four weeks of self-management education, while 45 patients
      received usual care. Patients were evaluated at baseline, at three months and one
      year following the educational intervention. The primary outcome variable was
      HRQoL measured by the St George's Respiratory Questionnaire (SGRQ). The secondary
      outcome variables were number of emergency room visits and hospitalizations for
      exacerbation. RESULTS: The intervention group's HRQoL improved significantly at
      three months (total score A = -5.0 [P = 0.006]) and 12 months (total score A = 
      6.7 [P < 0.001]), as evidenced by decreased scores on the SGRQ. In contrast, the
      SGRQ scores increased significantly in the control group at three months (total
      score A = +3.7 [P = 0.022]) and 12 months (total score A = +3.4 [P = 0.032]).
      Global impact appeared to be responsible for the change in the intervention
      group. Moreover, in the intervention group, the number of hospitalizations
      dropped from 0.7/person/year to 0.3/person/year (P = 0.017), and emergency room
      visits dropped from 1.1 person/year to 0.2/person/year (P = 0.002), while
      subjects in the control group did not experience any significant decreases in
      these parameters. CONCLUSIONS: A planned education program improved HRQoL while
      decreasing the number of emergency room visits and hospitalizations in patients
      with stable COPD; this improvement persisted at 12 months.

PMID- 21969936
TI  - Religious differences in female genital cutting: a case study from Burkina Faso.
AB  - The relationship between religious obligations and female genital cutting is
      explored using data from Burkina Faso, a religiously and ethnically diverse
      country where approximately three-quarters of adult women are circumcised. Data
      from the 2003 Burkina Faso Demographic and Health Survey are used to estimate
      multilevel models of religious variation in the intergenerational transmission of
      female genital cutting. Differences between Christians, Muslims, and adherents of
      traditional religions are reported, along with an assessment of the extent to
      which individual and community characteristics account for religious differences.
      Religious variation in the intergenerational transmission of female genital
      cutting is largely explained by specific religious beliefs and by contextual
      rather than individual characteristics. Although Muslim women are more likely to
      have their daughters circumcised, the findings suggest the importance of a
      collective rather than individual Muslim identity for the continuation of the
      practice.

PMID- 21969937
TI  - Religion and suicide acceptability: a cross-national analysis.
AB  - Four perspectives (moral community thesis, religious integration, religious
      commitment, and social networks) guide the selection of variables in this study.
      Data are from the combined World Values/European Values Surveys for 2000 (50,547
      individuals nested in 56 nations). The results of a multivariate hierarchical
      linear model support all four perspectives. Persons residing in nations with
      relatively high levels of religiosity, who are affiliated with one of four major
      faiths, are religiously committed, and are engaged with a religious network are
      found to be lower in suicide acceptability. The religious integration
      perspective, in particular, is empirically supported; affiliation with Islam is
      associated with low suicide acceptability. The findings provide strong support
      for an integrated model and demonstrate the usefulness of the moral community
      thesis in understanding suicide acceptability.

PMID- 21969938
TI  - Revised recommendations for yellow fever vaccination for international
      travellers, 2011.

PMID- 21969939
TI  - Performance of acute flaccid paralysis (AFP) surveillance and incidence of
      poliomyelitis, 2011.

PMID- 21969940
TI  - InterAmerican Conference on Onchocerciasis, 2010: progress towards eliminating
      river blindness in the WHO Region of the Americas.

PMID- 21969941
TI  - Health conditions for travellers to Saudi Arabia for the pilgrimage to Mecca
      (Hajj).

PMID- 21969942
TI  - Mass gatherings: implications and opportunities for global health security.

PMID- 21969943
TI  - Comparative, ecological, and developmental aspects of visual system design and
      function.

PMID- 21969944
TI  - Unwelcome viral stowaway: measles importation through air travel.

PMID- 21969946
TI  - Old World cutaneous leishmaiasis-not always just cutaneous.

PMID- 21969945
TI  - CDC Travelers' Health Branch releases free, web-based training course Yellow
      Fever: Information for Health Care Professionals Advising Travelers.

PMID- 21969947
TI  - Cytopenias and parvovirus infection.

PMID- 21969948
TI  - [More hospital admissions for malaria in Uganda].

PMID- 21969949
TI  - A contribution from Canada.

PMID- 21969950
TI  - [Treatment of pregnant women with depression: continuing need for a professional
      debate].

PMID- 21969951
TI  - [Transparency, reliability and conflict of interest].

PMID- 21969952
TI  - [Drug industry and publication practice].

PMID- 21969953
TI  - [Control should be counteracted].

PMID- 21969954
TI  - Hodgkin lymphoma in the central nervous system.

PMID- 21969956
TI  - Lasker Foundation honours malaria researcher.

PMID- 21969957
TI  - Ukraine failing to provide evidence-based palliative care.

PMID- 21969955
TI  - Glutathione as a signaling molecule:  another challenge to pathogens.
AB  - Plants harbor a variety of signaling molecules which are members of a vast array
      of signaling networks in maintaining their physiological balance. The well known
      members up till now are salicylic acid (SA), jasmonic acid (JA), ethylene (ET),
      abscissic acid (ABA) and reactive oxygen species (ROS) which are employed by
      plants for their adaptation to various environmental stresses in order to
      survive. GSH is gradually gaining importance and becoming a molecule of interest
      to a number of researchers especially in relation to plant defense to pathogens.
      Although the role of GSH in plant defense has long been known, a dearth of
      information still exists regarding the mechanism underlying this defense
      response. This review highlights on the progress made in the cross-communication
      of GSH with other established signaling molecules through which GSH acts in
      abating biotic stress

PMID- 21969958
TI  - Doodling and the default network of the brain.

PMID- 21969961
TI  - Study of heavy metal concentration and partitioning in the Estrela River:
      implications for the pollution in Guanabara Bay - SE Brazil.
AB  - In this study, the geochemical analysis of ten sediment samples collected along
      the fluvial system of the Estrela River, which flows into the northern portion of
      Guanabara Bay, shows the presence of anthropogenic impacts in this area.
      Concentrations of Fe, Mn, Zn, Cu, Pb, Cr and Ni obtained were slightly higher,
      when compared with values found in natural environments. The particle size and
      organic matter content in most of the analyzed stations showed features not
      conducive to the accumulation of pollutants due to the low organic matter content
      and the strong presence of sand fraction. There was also the fractionation of
      heavy metals in sediments and it was found the prominence of residual and
      reducible phase, besides the significant occurrence of organic fractions in some
      analyzed stations. These factors, thus, highlight the potential risks of
      contamination, where the metals associated with the organic phase can become
      bioavailable in processes of dissolution, provided by physico-chemical changes
      that can occur in this aquatic environment.

PMID- 21969960
TI  - Chemical composition and antimicrobial activity of essential oils of Ocimum canum
      Sims. and Ocimum selloi Benth.
AB  - This work describes the chemical composition and antimicrobial activity of the
      volatile oils of Ocimum canum and Ocimum selloi, both occurring in Jequie/BA,
      northeastern Brazil. The plants were collected in the winter/2005 and
      summer/2006, the oils extracted by steam distillation and further analyzed by GC
      MS. A total of 30 and 31 compounds was identified from the oils of O. selloi and
      O. canum, respectively. It was observed that the oil content of O. canum showed
      variation during the seasons, while the oils of O. selloi did not. Methylchavicol
      and linalool were the main chemical components found in the aerial parts and
      leaves of O. canum. This finding permitted to characterize this specimen as a new
      chemotype of O. canum. Regarding the aerial parts of O. selloi, eugenol, 1,8
      cineole, transcaryophyllene and linalool were identified as their major
      components. All extracted oils from the aerial parts showed biological activity
      against gram-positive cocci - Staphylococcus aureus ATCC 25923 - but only the O.
      canum one showed activity against gram-negative bacilli - Escherichia coli ATCC
      25922.

PMID- 21969962
TI  - Validation of a protocol to evaluate maximal expiratory pressure using a pressure
      transducer and a signal conditioner.
AB  - The respiratory muscles can present fatigue and even chronic inability to
      generate force. So, reliable devices are necessary to their evaluation. The aim
      of this study is to evaluate the MEP (Maximal Expiratory Pressure) values of
      individuals between 20 and 25 years old and to validate a protocol using a
      pressure transducer and a signal conditioner comparing it with the digital
      manometer. We evaluated the MEP of 10 participants. They remained seated and made
      six respiratory maneuvers from Total Lung Capacity (TLC) to Residual Volume (RV).
      The results in the study showed no statistically significant differences when
      compared to values reported in the literature, and that the pressure transducer
      provides reliable values for MEP.

PMID- 21969963
TI  - Comparison of estimators for measures of linkage disequilibrium.
AB  - The measurement of biallelic pair-wise association called linkage disequilibrium
      (LD) is an important issue in order to understand the genomic architecture. A
      plethora of measures of association in two by two tables have been proposed in
      the literature. Beside the problem of choosing an appropriate measure, the
      problem of their estimation has been neglected in the literature. It needs to be
      emphasized that the definition of a measure and the choice of an estimator
      function for it are conceptually unrelated tasks. In this paper, we compare the
      performance of various estimators for the three popular LD measures D', r and Y
      in a simulation study for small to moderate samples sizes (N<=500). The usual
      frequency-plug-in estimators can lead to unreliable or undefined estimates.
      Estimators based on the computationally expensive volume measures have been
      proposed recently as a remedy to this well-known problem. We confirm that volume
      estimators have better expected mean square error than the naive plug-in
      estimators. But they are outperformed by estimators plugging-in easy to calculate
      non-informative Bayesian probability estimates into the theoretical formulae for
      the measures. Fully Bayesian estimators with non-informative Dirichlet priors
      have comparable accuracy but are computationally more expensive. We recommend the
      use of non-informative Bayesian plug-in estimators based on Jeffreys' prior, in
      particular when dealing with SNP array data where the occurrence of small table
      entries and table margins is likely.

PMID- 21969964
TI  - Sensitivity of understorey bird species in two different successional stages of
      the lowland Atlantic Forest, Brazil.
AB  - The Atlantic Forest has a high destruction rate and there is little information
      available on some aspects of the neotropical bird biology. Changes in environment
      are important factors that affect the resources available to birds. We compared
      the species sensitivity level of understorey birds in two areas in distinct
      successional stages (primary and secondary sections). Two 100 ha plots of lowland
      Atlantic Forest were analysed between August and December 2006. Among 25 bird
      species recorded, thirteen had lower abundance in secondary forest, two in
      primary forest, and ten had not clear tendency. According to the criteria used,
      the percentages for species with low, and medium and high sensitivity to habitat
      change were 44% and 56%, respectively. The number of species was not associated
      with the endemism level or foraging strata. Results show the importance of
      knowing bird species' sensitivity level with regard to habitat modification, and
      not only forest fragmentation.

PMID- 21969965
TI  - Liposomal photosensitizers: potential platforms for anticancer photodynamic
      therapy.
AB  - Photodynamic therapy is a well-established and clinically approved treatment for
      several types of cancer. Antineoplastic photodynamic therapy is based on
      photosensitizers, i.e., drugs that absorb photons translating light energy into a
      chemical potential that damages tumor tissues. Despite the encouraging clinical
      results with the approved photosensitizers available today, the prolonged skin
      phototoxicity, poor selectivity for diseased tissues, hydrophobic nature, and
      extended retention in the host organism shown by these drugs have stimulated
      researchers to develop new formulations for photodynamic therapy. In this
      context, due to their amphiphilic characteristic (compatibility with both
      hydrophobic and hydrophilic substances), liposomes have proven to be suitable
      carriers for photosensitizers, improving the photophysical properties of the
      photosensitizers. Moreover, as nanostructured drug delivery systems, liposomes
      improve the efficiency and safety of antineoplastic photodynamic therapy, mainly
      by the classical phenomenon of extended permeation and retention. Therefore, the
      association of photosensitizers with liposomes has been extensively studied. In
      this review, both current knowledge and future perspectives on liposomal carriers
      for antineoplastic photodynamic therapy are critically discussed.

PMID- 21969966
TI  - Comparing mortality in renal patients on hemodialysis versus peritoneal dialysis
      using a marginal structural model.
AB  - When comparing the causal effect of peritoneal dialysis (PD) and hemodialysis
      (HD) treatment on lowering mortality in renal patients, using observational data,
      it is necessary to adjust for different forms of confounding and informative
      censoring. Both the type of dialysis treatment that is started with and mortality
      are affected by baseline covariates. Longitudinal and baseline variables can
      affect both the probability of switching from one type of dialysis to the other,
      and mortality. Longitudinal and baseline variables can also affect the
      probability of receiving a kidney transplant, possibly causing informative
      censoring. Adjusting for longitudinal variables by including them as covariates
      in a regression model potentially causes bias, for instance by losing a possible
      indirect effect of dialysis on mortality via these longitudinal variables.
      Instead, we fitted a marginal structural model (MSM) to estimate the causal
      effect of dialysis type, adjusted for confounding and informative censoring. We
      used the MSM to compare the hazard of death as well as cumulative survival
      between the potential treatment trajectories "always PD" and "always HD" over
      time, conditional on age and diabetes mellitus status. We used inverse
      probability weighting (IPW) to fit the MSM.

PMID- 21969967
TI  - Estimation of modified concordance ratio in sib-pairs: effect of consanguinity on
      the risk of congenital heart diseases.
AB  - Family studies are widely used for research into genetic and environmental
      influences on human traits. In this paper, we establish statistical methodology
      for the estimation of a new measure of sib similarity with respect to dichotomous
      traits measured on each member of within family sib-pair. We call this parameter
      "excess risk." For inference problems involving a single sample, we construct a
      large sample confidence interval on the concerned parameter. It has long been
      suspected that consanguinity is a risk factor for many genetic defects.
      Therefore, we establish a procedure to test the significance of the difference
      between excess risk parameters in a sample of consanguineous marriages and
      another sample of non-consanguineous marriages. We apply the methodology to data
      from a hospital-based congenital heart defects registry in Saudi Arabia, a
      population in which consanguinity is quite common.

PMID- 21969968
TI  - Comparison of variable selection approaches for dynamic treatment regimes.
AB  - In estimating optimal adaptive treatment strategies, the tailor treatment
      variables used for patient profiles are typically hand-picked by experts. However
      these variables may not yield an estimated optimal dynamic regime that is close
      to the optimal regime which uses all variables. The question of selecting
      tailoring variables has not yet been answered satisfactorily, though promising
      new approaches have been proposed. We compare the use of reducts--a variable
      selection tool from computer sciences--to the S-score criterion proposed by
      Gunter and colleagues in 2007 for suggesting collections of useful variables for
      treatment regime tailoring. Although the reducts-based approach promised several
      advantages such as the ability to account for correlation among tailoring
      variables, it proved to have several undesirable properties. The S-score
      performed better, though it too exhibited some disappointing qualities.

PMID- 21969969
TI  - A pseudo-EM algorithm for clustering incomplete longitudinal data.
AB  - A method for clustering incomplete longitudinal data, and gene expression time
      course data in particular, is presented. Specifically, an existing method that
      utilizes mixtures of multivariate Gaussian distributions with modified Cholesky
      decomposed covariance structure is extended to accommodate incomplete data.
      Parameter estimation is carried out in a fashion that is similar to an
      expectation-maximization algorithm. We focus on the particular application of
      clustering incomplete gene expression time course data. In this application, our
      approach gives good clustering performance when compared to the results when
      there is no missing data. Possible extensions of this work are also suggested.

PMID- 21969970
TI  - A corrected likelihood approach for the nonlinear transformation model with
      application to fluorescence lifetime measurements using exponential mixtures.
AB  - A fast and efficient estimation method is proposed that compensates the
      distortion in nonlinear transformation models. A likelihood-based estimator is
      developed that can be computed by an EM-type algorithm. The consistency of the
      estimator is shown and its limit distribution is provided. The new estimator is
      particularly well suited for fluorescence lifetime measurements, where only the
      shortest arrival time of a random number of emitted fluorescence photons can be
      detected and where arrival times are often modeled by a mixture of exponential
      distributions. The method is evaluated on real and synthetic data. Compared to
      currently used methods in fluorescence, the new estimator should allow a
      reduction of the acquisition time of an order of magnitude.

PMID- 21969971
TI  - Confidence intervals for negative binomial random variables of high dispersion.
AB  - We consider the problem of constructing confidence intervals for the mean of a
      Negative Binomial random variable based upon sampled data. When the sample size
      is large, it is a common practice to rely upon a Normal distribution
      approximation to construct these intervals. However, we demonstrate that the
      sample mean of highly dispersed Negative Binomials exhibits a slow convergence in
      distribution to the Normal as a function of the sample size. As a result,
      standard techniques (such as the Normal approximation and bootstrap) will
      construct confidence intervals for the mean that are typically too narrow and
      significantly undercover at small sample sizes or high dispersions. To address
      this problem, we propose techniques based upon Bernstein's inequality or the
      Gamma and Chi Square distributions as alternatives to the standard methods. We
      investigate the impact of imposing a heuristic assumption of boundedness on the
      data as a means of improving the Bernstein method. Furthermore, we propose a
      ratio statistic relating the Negative Binomial's parameters that can be used to
      ascertain the applicability of the Chi Square method and to provide guidelines on
      evaluating the length of all proposed methods. We compare the proposed methods to
      the standard techniques in a variety of simulation experiments and consider data
      arising in the serial analysis of gene expression and traffic flow in a
      communications network.

PMID- 21969972
TI  - Ordinal regression models for continuous scales.
AB  - Ordinal regression analysis is a convenient tool for analyzing ordinal response
      variables in the presence of covariates. In this paper we extend this methodology
      to the case of continuous self-rating scales such as the Visual Analog Scale
      (VAS) used in pain assessment, or the Linear Analog Self-Assessment (LASA) scales
      in quality of life studies. These scales measure subjects' perception of an
      intangible quantity, and cannot be handled as ratio variables because of their
      inherent nonlinearity. We express the likelihood in terms of a function
      connecting the scale with an underlying continuous latent variable and
      approximate this function either parametrically or non-parametrically. Then a
      general semi-parametric regression framework for continuous scales is developed.
      Two data sets have been analyzed to compare our method to the standard discrete
      ordinal regression model, and the parametric to the non-parametric versions of
      the model. The first data set uses VAS data from a study on the efficacy of low
      level laser therapy in the treatment of chronic neck pain; the second comes from
      a study on chemotherapy treatments in advanced breast cancer and looks at the
      impact of different drugs on patients' quality of life. The continuous
      formulation of the ordinal regression model has the advantage of no loss of
      precision due to categorization of the scores and no arbitrary choice of the
      number and boundaries of categories. The semi-parametric form of the model makes
      it a flexible method for analysis of continuous ordinal scales.

PMID- 21969973
TI  - Evaluation of incidence rates in pre-clinical studies using a Williams-type
      procedure.
AB  - The analysis of dose-response relationships is a common problem in pre-clinical
      studies. For example, proportions such as mortality rates and histopathological
      findings are of particular interest in repeated toxicity studies. Commonly
      applied designs consist of an untreated control group and several, possibly
      unequally spaced, dosage groups. The Williams test can be formulated as a
      multiple contrast test and is a powerful option to evaluate such data. In this
      paper, we consider simultaneous inference for Williams-type multiple contrasts
      when the response variable is binomial and sample sizes are only moderate.
      Approximate simultaneous confidence limits can be constructed using the quantiles
      of a multivariate normal distribution taking the correlation into account.
      Alternatively, multiplicity-adjusted p-values can be calculated as well. A
      simulation study shows that a simple correction based on adding pseudo
      observations leads to acceptable performance for moderate sample sizes, such as
      40 per group. In addition, the calculation of adjusted p-values and approximate
      power is presented. Finally, the proposed methods are applied to example data
      from two toxicological studies; the methods are available in an R-package.

PMID- 21969974
TI  - A unified approach for nonparametric evaluation of agreement in method comparison
      studies.
AB  - We present a nonparametric methodology for evaluation of agreement between
      multiple methods of measurement of a continuous variable. Our approach is unified
      in that it can deal with any scalar measure of agreement currently available in
      the literature, and can incorporate repeated and unreplicated measurements, and
      balanced as well as unbalanced designs. Our key idea is to treat an agreement
      measure as a functional of the joint cumulative distribution function of the
      measurements from multiple methods. This measure is estimated nonparametrically
      by plugging-in a weighted empirical counterpart of the joint distribution
      function. The resulting estimator is shown to be asymptotically normal under some
      specified assumptions. A closed-form expression is provided for the asymptotic
      standard error of the estimator. This asymptotic normality is used to derive a
      large-sample distribution-free methodology for simultaneously comparing the
      multiple measurement methods. The small-sample performance of this methodology is
      investigated via simulation. The asymptotic efficiency of the proposed
      nonparametric estimator relative to the normality-based maximum likelihood
      estimator is also examined. The methodology is illustrated by applying it to a
      blood pressure data set involving repeated measurements from three measurement
      methods.

PMID- 21969975
TI  - A principal stratification approach to assess the differences in prognosis
      between cancers caused by hormone replacement therapy and by other factors.
AB  - Several recent studies have reported that women who have used hormone replacement
      therapy (HRT), and developed breast cancer, tend to have a better prognosis than
      women with breast cancer who have not used HRT. One possible explanation is that
      tumors caused by HRT are more benign than tumors caused by other factors.
      Although it is relevant to quantify differences in prognostic factors across
      subtypes of breast cancer, it is not obvious how to do this correctly. This is
      because the tumors which occur among women who are treated with HRT are a mixture
      of HRT-induced and other tumors. We propose a framework based on principal
      stratification to distinguish women with HRT-induced tumors from women with
      tumors caused by other factors. To estimate the difference in prognosis for these
      two groups, we propose two estimation methods, which can be used under both
      cohort and case-control sampling schemes.

PMID- 21969976
TI  - Collaborative targeted maximum likelihood for time to event data.
AB  - Current methods used to analyze time to event data either rely on highly
      parametric assumptions which result in biased estimates of parameters which are
      purely chosen out of convenience, or are highly unstable because they ignore the
      global constraints of the true model. By using Targeted Maximum Likelihood
      Estimation (TMLE) one may consistently estimate parameters which directly answer
      the statistical question of interest. Targeted Maximum Likelihood Estimators are
      substitution estimators, which rely on estimating the underlying distribution.
      However, unlike other substitution estimators, the underlying distribution is
      estimated specifically to reduce bias in the estimate of the parameter of
      interest. We will present here an extension of TMLE for observational time to
      event data, the Collaborative Targeted Maximum Likelihood Estimator (C-TMLE) for
      the treatment specific survival curve. Through the use of a simulation study we
      will show that this method improves on commonly used methods in both robustness
      and efficiency. In fact, we will show that in certain situations the C-TMLE
      produces estimates whose mean square error is lower than the semi-parametric
      efficiency bound. We will also demonstrate that a semi-parametric efficient
      substitution estimator (TMLE) outperforms a semi-parametric efficient non
      substitution estimator (the Augmented Inverse Probability Weighted estimator) in
      sparse data situations. Lastly, we will show that the bootstrap is able to
      produce valid 95 percent confidence intervals in sparse data situations, while
      influence curve based inference breaks down.

PMID- 21969977
TI  - WHO framework targets tuberculosis-diabetes link.

PMID- 21969978
TI  - A stochastic EM type algorithm for parameter estimation in models with continuous
      outcomes, under complex ascertainment.
AB  - Outcome-dependent sampling probabilities can be used to increase efficiency in
      observational studies. For continuous outcomes, appropriate consideration of
      sampling design in estimating parameters of interest is often computationally
      cumbersome. In this article, we suggest a Stochastic EM type algorithm for
      estimation when ascertainment probabilities are known or estimable. The
      computational complexity of the likelihood is avoided by filling in missing data
      so that an approximation of the full data likelihood can be used. The method is
      not restricted to any specific distribution of the data and can be used for a
      broad range of statistical models.

PMID- 21969979
TI  - Critical conversations: navigating between hope and truth.

PMID- 21969980
TI  - Simple nonparametric confidence regions for the evaluation of continuous-scale
      diagnostic tests.
AB  - The evaluation of the ability of a diagnostic test to separate diseased subjects
      from non-diseased subjects is a crucial issue in modern medicine. The accuracy of
      a continuous-scale test at a chosen cut-off level can be measured by its
      sensitivity and specificity, i.e. by the probabilities that the test correctly
      identifies the diseased and non-diseased subjects, respectively. In practice,
      sensitivity and specificity of the test are unknown. Moreover, which cut-off
      level to use is also generally unknown in that no preliminary indications driving
      its choice could be available. In this paper, we address the problem of making
      joint inference on pairs of quantities defining accuracy of a diagnostic test, in
      particular, when one of the two quantities is the cut-off level. We propose a
      technique based on an empirical likelihood statistic that allows, within a
      unified framework, to build bivariate confidence regions for the pair
      (sensitivity, cut-off level) at a fixed value of specificity as well as for the
      pair (specificity, cut-off level) at a fixed value of sensitivity or the pair
      (sensitivity, specificity) at a fixed cut-off value. A simulation study is
      carried out to assess the finite-sample accuracy of the method. Moreover, we
      apply the method to two real examples.

PMID- 21969981
TI  - Bivariate zero-inflated regression for count data: a Bayesian approach with
      application to plant counts.
AB  - Lately, bivariate zero-inflated (BZI) regression models have been used in many
      instances in the medical sciences to model excess zeros. Examples include the BZI
      Poisson (BZIP), BZI negative binomial (BZINB) models, etc. Such formulations vary
      in the basic modeling aspect and use the EM algorithm (Dempster, Laird and Rubin,
      1977) for parameter estimation. A different modeling formulation in the Bayesian
      context is given by Dagne (2004). We extend the modeling to a more general
      setting for multivariate ZIP models for count data with excess zeros as proposed
      by Li, Lu, Park, Kim, Brinkley and Peterson (1999), focusing on a particular
      bivariate regression formulation. For the basic formulation in the case of
      bivariate data, we assume that Xi are (latent) independent Poisson random
      variables with parameters lambda i, i = 0, 1, 2. A bi-variate count vector (Y1,
      Y2) response follows a mixture of four distributions; p0 stands for the mixing
      probability of a point mass distribution at (0, 0); p1, the mixing probability
      that Y2 = 0, while Y1 = X0 + X1; p2, the mixing probability that Y1 = 0 while Y2
      = X0 + X2; and finally (1 - p0 - p1 - p2), the mixing probability that Yi = Xi +
      X0, i = 1, 2. The choice of the parameters {pi, lambda i, i = 0, 1, 2} ensures
      that the marginal distributions of Yi are zero inflated Poisson (lambda 0 +
      lambda i). All the parameters thus introduced are allowed to depend on co
      variates through canonical link generalized linear models (McCullagh and Nelder,
      1989). This flexibility allows for a range of real-life applications, especially
      in the medical and biological fields, where the counts are bivariate in nature
      (with strong association between the processes) and where there are excess of
      zeros in one or both processes. Our contribution in this paper is to employ a
      fully Bayesian approach consolidating the work of Dagne (2004) and Li et al.
      (1999) generalizing the modeling and sampling-based methods described by Ghosh,
      Mukhopadhyay and Lu (2006) to estimate the parameters and obtain posterior
      credible intervals both in the case where co-variates are not available as well
      as in the case where they are. In this context, we provide explicit data
      augmentation techniques that lend themselves to easier implementation of the
      Gibbs sampler by giving rise to well-known and closed-form posterior
      distributions in the bivariate ZIP case. We then use simulations to explore the
      effectiveness of this estimation using the Bayesian BZIP procedure, comparing the
      performance to the Bayesian and classical ZIP approaches. Finally, we demonstrate
      the methodology based on bivariate plant count data with excess zeros that was
      collected on plots in the Phoenix metropolitan area and compare the results with
      independent ZIP regression models fitted to both processes.

PMID- 21969982
TI  - Fast function-on-scalar regression with penalized basis expansions.
AB  - Regression models for functional responses and scalar predictors are often fitted
      by means of basis functions, with quadratic roughness penalties applied to avoid
      overfitting. The fitting approach described by Ramsay and Silverman in the 1990 s
      amounts to a penalized ordinary least squares (P-OLS) estimator of the
      coefficient functions. We recast this estimator as a generalized ridge regression
      estimator, and present a penalized generalized least squares (P-GLS) alternative.
      We describe algorithms by which both estimators can be implemented, with
      automatic selection of optimal smoothing parameters, in a more computationally
      efficient manner than has heretofore been available. We discuss pointwise
      confidence intervals for the coefficient functions, simultaneous inference by
      permutation tests, and model selection, including a novel notion of pointwise
      model selection. P-OLS and P-GLS are compared in a simulation study. Our methods
      are illustrated with an analysis of age effects in a functional magnetic
      resonance imaging data set, as well as a reanalysis of a now-classic Canadian
      weather data set. An R package implementing the methods is publicly available.

PMID- 21969983
TI  - Panel count data regression with informative observation times.
AB  - When patients are monitored for potentially recurrent events such as infections
      or tumor metastases, it is common for clinicians to ask patients to come back
      sooner for follow-ups based on the results of the most recent exam. This means
      that subjects' observation times will be irregular and related to subject
      specific factors. Previously proposed methods for handling such panel count data
      assume that the dependence between the events process and the observation time
      process is governed by time-independent factors. This article considers
      situations where the observation times are predicted by time-varying factors such
      as the outcome observed at the last visit or cumulative exposure. Using a joint
      modelling approach, we propose a class of inverse-intensity-rate-ratio weighted
      estimators that are root-n consistent and asymptotically normal. The proposed
      estimators use estimating equations and are fairly simple and easy to compute. We
      demonstrate the performance of the method using simulated data and illustrate the
      approach using a cancer study dataset.

PMID- 21969984
TI  - Sample size requirements for interval estimation of the kappa statistic for
      interobserver agreement studies with a binary outcome and multiple raters.
AB  - Sample size requirements that achieve a prespecified expected lower limit for a
      confidence interval about the intraclass kappa statistic are supplied for the
      case of multiple raters and a binary outcome variable. The expected lower
      confidence limit achievable for a given number of subjects and raters is also
      presented. These results should be useful in the planning stages of an
      interobserver agreement study in which the focus is on interval estimation rather
      than hypothesis-testing.

PMID- 21969985
TI  - A small sample correction for estimating attributable risk in case-control
      studies.
AB  - The attributable risk, often called the population attributable risk, is in many
      epidemiological contexts a more relevant measure of exposure-disease association
      than the excess risk, relative risk, or odds ratio. When estimating attributable
      risk with case-control data and a rare disease, we present a simple bias
      correction to the standard approach, which also makes it more stable and less
      variable. As with analogous corrections given by Jewell (1986) for other measures
      of association, the adjustment often won't make a substantial difference unless
      the sample size is very small or point estimates are desired within fine strata,
      but we discuss the possible utility for applications.

PMID- 21969986
TI  - Two-level stochastic search variable selection in GLMs with missing predictors.
AB  - Stochastic search variable selection (SSVS) algorithms provide an appealing and
      widely used approach for searching for good subsets of predictors while
      simultaneously estimating posterior model probabilities and model-averaged
      predictive distributions. This article proposes a two-level generalization of
      SSVS to account for missing predictors while accommodating uncertainty in the
      relationships between these predictors. Bayesian approaches for allowing
      predictors that are missing at random require a model on the joint distribution
      of the predictors. We show that predictive performance can be improved by
      allowing uncertainty in the specification of predictor relationships in this
      model. The methods are illustrated through simulation studies and analysis of an
      epidemiologic data set.

PMID- 21969987
TI  - Survival models in health economic evaluations: balancing fit and parsimony to
      improve prediction.
AB  - Health economic decision models compare costs and health effects of different
      interventions over the long term and usually incorporate survival data. Since
      survival is often extrapolated beyond the range of the data, inaccurate model
      specification can result in very different policy decisions. However, in this
      area, flexible survival models are rarely considered, and model uncertainty is
      rarely accounted for. In this article, various survival distributions are applied
      in a decision model for oral cancer screening. Flexible parametric models are
      compared with Bayesian semiparametric models, in which the baseline hazard can be
      made arbitrarily complex while still enabling survival to be extrapolated. A
      fully Bayesian framework is used for all models so that uncertainties can be
      easily incorporated in estimates of long-term costs and effects. The fit and
      predictive ability of both parametric and semiparametric models are compared
      using the deviance information criterion in order to account for model
      uncertainty in the cost-effectiveness analysis. Under the Bayesian semiparametric
      models, some smoothing of the hazard function is required to obtain adequate
      predictive ability and avoid sensitivity to the choice of prior. We determine
      that one flexible parametric survival model fits substantially better than the
      others considered in the oral cancer example.

PMID- 21969988
TI  - Interval estimation of some epidemiological measures of association.
AB  - In epidemiological cohort studies, the probability of developing a disease for
      individuals in a treatment/intervention group is compared with that of a control
      group. The groups involve varying cluster sizes, and the binary responses within
      each cluster cannot be assumed independently. Three major measures of association
      used to report the efficacy of treatments or effectiveness of public health
      intervention programs in case of prospective studies are Risk Difference (RD),
      Risk Ratio (RR) and Relative Risk Difference (RED). The preference of one measure
      of association over the other in drawing statistical inference depends on design
      of study. Lui (2004) discusses a number of methods of constructing confidence
      intervals for each of these measures. Specifically, Lui (2004) discusses four
      methods for RD, four methods for RR and three methods for RED. For the
      construction of confidence intervals for RD, Paul and Zaihra (2008) compare the
      four methods discussed by Lui (2004), using extensive simulations with a method
      based on an estimator of the variance of a ratio estimator by Cochran (1977) and
      a method based on a sandwich estimator of the variance of the regression
      estimator using the generalized estimating equations approach of Zeger and Liang
      (1986). Paul and Zaihra (2008) conclude that the method based on an estimate of
      the variance of a ratio estimator performs best overall. In this paper, we extend
      the two new methodologies introduced in Paul and Zaihra (2008) to confidence
      interval construction of the risk measures RR and RED. Extensive simulations show
      that the method based on an estimate of the variance of a ratio estimator
      performs best overall for constructing confidence interval for the other two risk
      measures RR and RED as well. This method involves a very simple variance
      expression which can be implemented with a very few computer codes. Therefore, it
      can be considered as an easily implementable alternative for all the three
      measures of association.

PMID- 21969989
TI  - Comment: Analyzing propensity score matched count data.
AB  - We offer an explanation to the simulation result of Austin (2009) regarding rate
      ratios, and argue that unmatched analysis of propensity score matched count data
      results in conservative statistical inferences on the rate ratios.

PMID- 21969990
TI  - Systematic review on the efficacy of fexofenadine in seasonal allergic rhinitis:
      a meta-analysis of randomized, double-blind, placebo-controlled clinical trials.
AB  - RATIONALE: Evidence-based medicine represents the effort to highlight the best
      intervention for patients, clinicians, and policy makers, each from their
      respective viewpoint, to solve a particular health condition. According to a
      recently diffused grading system of evidence and recommendations for medical
      interventions, efficacy and safety represent 2 of the most important features to
      consider, and data from meta-analyses of randomized controlled clinical trials
      (RCTs) is the strongest supporting demonstration. Fexofenadine has been used for
      its efficacy and safety in the treatment of allergic rhinitis (AR) for many years
      although no meta-analyses supporting its use currently exist. The aim of this
      study is to assess for the first time the efficacy and safety of fexofenadine in
      the treatment of AR by means of a meta-analytic analysis of existing RCTs. Since
      specific evidence should be provided to address recommendations in a pediatric
      population, the quality of the estimates of this subgroup analysis is assessed.
      METHODS: All double-blind, placebo-controlled randomized trials assessing the
      efficacy of fexofenadine in AR were searched for in OVID, Medline, and Embase
      databases up to December 2007. Outcomes were extracted from original articles;
      when this information was not available, the authors of each trial were
      contacted. Some graphics were digitalized. The RevMan 5 program was used to
      perform the analysis. GradePro 3.2.2 was used to assess the quality of the
      evidence for a pediatric population. RESULTS: Of 2,152 identified articles, 20
      were potentially relevant trials. Eight studies satisfied the inclusion criteria
      and were included in the meta-analysis. The main reasons for exclusion were:
      unnatural exposure, strong study limitations, an atypical outcome measurement, a
      design for other outcomes, and not being a placebo-controlled, single-blind
      study. Seven trials investigated a mixed population of adults and children, 1
      trial investigated only children, and 1 trial only adults. In 1,833 patients
      receiving fexofenadine (1,699 placebo), a significant reduction of the daily
      reflective total symptom scores (TSS) (SMD -0.42; 95% CI -0.49 to -0.35, p <
      0.00001) was found. Positive results were also found for morning instantaneous
      TSS and individual nasal symptom scores (sneezing, rhinorrhea, itching, and
      congestion). The safety analysis did not show a significant difference in
      reported adverse events (AE) between the active and placebo treatment groups (OR
      = 1.03; 95% CI 0.87-1.22, p = 0.75). A very low heterogeneity between the studies
      was detected, so a fixed-effects model was used. The mean quality level of the
      included trials was medium. Specific information for a pediatric population may
      be assumed with a moderate quality of evidence from only 1 study and with a low
      quality of evidence, mainly due to indirectness, from the others. CONCLUSIONS:
      This study has 5 major strengths: it represents the first attempt to evaluate the
      efficacy and safety of fexofenadine in the treatment of AR by means of a meta
      analysis of RCTs; there was consistency between positive results in terms of
      efficacy in TSS and in individual symptoms; a large population was studied; there
      was an irrelevant interstudy heterogeneity, and the AE frequency was similar in
      both groups. All of these values encourage the recommendation of fexofenadine for
      AR. Further research focused on the benefits and disadvantages for a pediatric
      population is needed.

PMID- 21969991
TI  - Special issue on causal inference.
AB  - We provide a brief editorial introduction to a special issue of The International
      Journal of Biostatistics dedicated to several papers presented at a workshop held
      at the Banff International Research Station, Canada, in May 2009.

PMID- 21969992
TI  - Targeted maximum likelihood based causal inference: Part I.
AB  - Given causal graph assumptions, intervention-specific counterfactual
      distributions of the data can be defined by the so called G-computation formula,
      which is obtained by carrying out these interventions on the likelihood of the
      data factorized according to the causal graph. The obtained G-computation formula
      represents the counterfactual distribution the data would have had if this
      intervention would have been enforced on the system generating the data. A causal
      effect of interest can now be defined as some difference between these
      counterfactual distributions indexed by different interventions. For example, the
      interventions can represent static treatment regimens or individualized treatment
      rules that assign treatment in response to time-dependent covariates, and the
      causal effects could be defined in terms of features of the mean of the treatment
      regimen specific counterfactual outcome of interest as a function of the
      corresponding treatment regimens. Such features could be defined
      nonparametrically in terms of so called (nonparametric) marginal structural
      models for static or individualized treatment rules, whose parameters can be
      thought of as (smooth) summary measures of differences between the treatment
      regimen specific counterfactual distributions. In this article, we develop a
      particular targeted maximum likelihood estimator of causal effects of multiple
      time point interventions. This involves the use of loss-based super-learning to
      obtain an initial estimate of the unknown factors of the G-computation formula,
      and subsequently, applying a target-parameter specific optimal fluctuation
      function (least favorable parametric submodel) to each estimated factor,
      estimating the fluctuation parameter(s) with maximum likelihood estimation, and
      iterating this updating step of the initial factor till convergence. This
      iterative targeted maximum likelihood updating step makes the resulting estimator
      of the causal effect double robust in the sense that it is consistent if either
      the initial estimator is consistent, or the estimator of the optimal fluctuation
      function is consistent. The optimal fluctuation function is correctly specified
      if the conditional distributions of the nodes in the causal graph one intervenes
      upon are correctly specified. The latter conditional distributions often comprise
      the so called treatment and censoring mechanism. Selection among different
      targeted maximum likelihood estimators (e.g., indexed by different initial
      estimators) can be based on loss-based cross-validation such as likelihood based
      cross-validation or cross-validation based on another appropriate loss function
      for the distribution of the data. Some specific loss functions are mentioned in
      this article. Subsequently, a variety of interesting observations about this
      targeted maximum likelihood estimation procedure are made. This article provides
      the basis for the subsequent companion Part II-article in which concrete
      demonstrations for the implementation of the targeted MLE in complex causal
      effect estimation problems are provided.

PMID- 21969993
TI  - Balancing and elimination of nuisance variables.
AB  - Addressing covariate imbalance in causal analysis will be reformulated as an
      elimination of the nuisance variables problem. We show, within a counterfactual
      balanced setting, how averaging, conditioning, and marginalization techniques can
      be used to reduce bias due to a possibly large number of imbalanced baseline
      confounders. The notions of X-sufficient and X-ancillary quantities are discussed
      and, as an example, we show how sliced inverse regression and related methods
      from regression theory that estimate a basis for a central sufficient subspace
      provide alternative summaries to propensity based analysis. Examples for
      exponential families and elliptically symmetric families of distributions are
      provided.

PMID- 21969994
TI  - Dynamic regime marginal structural mean models for estimation of optimal dynamic
      treatment regimes, Part I: main content.
AB  - Dynamic treatment regimes are set rules for sequential decision making based on
      patient covariate history. Observational studies are well suited for the
      investigation of the effects of dynamic treatment regimes because of the
      variability in treatment decisions found in them. This variability exists because
      different physicians make different decisions in the face of similar patient
      histories. In this article we describe an approach to estimate the optimal
      dynamic treatment regime among a set of enforceable regimes. This set is
      comprised by regimes defined by simple rules based on a subset of past
      information. The regimes in the set are indexed by a Euclidean vector. The
      optimal regime is the one that maximizes the expected counterfactual utility over
      all regimes in the set. We discuss assumptions under which it is possible to
      identify the optimal regime from observational longitudinal data. Murphy et al.
      (2001) developed efficient augmented inverse probability weighted estimators of
      the expected utility of one fixed regime. Our methods are based on an extension
      of the marginal structural mean model of Robins (1998, 1999) which incorporate
      the estimation ideas of Murphy et al. (2001). Our models, which we call dynamic
      regime marginal structural mean models, are specially suitable for estimating the
      optimal treatment regime in a moderately small class of enforceable regimes of
      interest. We consider both parametric and semiparametric dynamic regime marginal
      structural models. We discuss locally efficient, double-robust estimation of the
      model parameters and of the index of the optimal treatment regime in the set. In
      a companion paper in this issue of the journal we provide proofs of the main
      results.

PMID- 21969995
TI  - Selective ignorability assumptions in causal inference.
AB  - Most attempts at causal inference in observational studies are based on
      assumptions that treatment assignment is ignorable. Such assumptions are usually
      made casually, largely because they justify the use of available statistical
      methods and not because they are truly believed. It will often be the case that
      it is plausible that conditional independence holds at least approximately for a
      subset but not all of the experience giving rise to one's data. Such selective
      ignorability assumptions may be used to derive valid causal inferences in
      conjunction with structural nested models. In this paper, we outline selective
      ignorability assumptions mathematically and sketch how they may be used along
      with otherwise standard G-estimation or likelihood-based methods to obtain
      inference on structural nested models. We also consider use of these assumptions
      in the presence of selective measurement error or missing data when the
      missingness is not at random. We motivate and illustrate our development by
      considering an analysis of an observational database to estimate the effect of
      erythropoietin use on mortality among hemodialysis patients.

PMID- 21969996
TI  - Model checking with residuals for g-estimation of optimal dynamic treatment
      regimes.
AB  - In this paper, we discuss model checking with residual diagnostic plots for g
      estimation of optimal dynamic treatment regimes. The g-estimation method requires
      three different model specifications at each treatment interval under
      consideration: (1) the blip model; (2) the expected counterfactual model; and (3)
      the propensity model. Of these, the expected counterfactual model is especially
      difficult to specify correctly in practice and so far there has been little
      guidance as to how to check for model misspecification. Residual plots are a
      useful and standard tool for model diagnostics in the classical regression
      setting; we have adapted this approach for g-estimation. We demonstrate the
      usefulness of our approach in a simulation study, and apply it to real data in
      the context of estimating the optimal time to stop breastfeeding.

PMID- 21969997
TI  - Accuracy of conventional and marginal structural Cox model estimators: a
      simulation study.
AB  - Marginal structural models (MSM) provide a powerful tool to control for
      confounding by a time-dependent covariate without inappropriately adjusting for
      its role as a variable affected by treatment (Hernan et al., 2000). In this
      paper, we demonstrate that it is possible to fit a marginal structural Cox model
      directly, rather than the typical approach of using pooled logistic regression,
      using the weighted Cox proportional hazards function that has been implemented in
      standard software. To evaluate the performance of the marginal structural Cox
      model directly via inverse probability of treatment weighting, we conducted
      several simulation studies based on two data-generating models: one which
      replicates the simulations of Young et al. (2009) and an additional, more
      clinically plausible approach which mimics survival data with time-dependent
      confounders and time-varying treatment. Using the simulations, we illustrate the
      limitations of the conventional time-dependent Cox model and the MSM fitted via
      pooled logistic regression. Furthermore, we propose two novel normalized weights
      with the goal of reducing the MSM estimators' variability. The performance of the
      normalized weights is evaluated alongside the usual unstabilized and stabilized
      weights.

PMID- 21969998
TI  - Comparing approaches to causal inference for longitudinal data: inverse
      probability weighting versus propensity scores.
AB  - In observational studies for causal effects, treatments are assigned to
      experimental units without the benefits of randomization. As a result, there is
      the potential for bias in the estimation of the treatment effect. Two methods for
      estimating the causal effect consistently are Inverse Probability of Treatment
      Weighting (IPTW) and the Propensity Score (PS). We demonstrate that in many
      simple cases, the PS method routinely produces estimators with lower Mean-Square
      Error (MSE). In the longitudinal setting, estimation of the causal effect of a
      time-dependent exposure in the presence of time-dependent covariates that are
      themselves affected by previous treatment also requires adjustment approaches. We
      describe an alternative approach to the classical binary treatment propensity
      score termed the Generalized Propensity Score (GPS). Previously, the GPS has
      mainly been applied in a single interval setting; we use an extension of the GPS
      approach to the longitudinal setting. We compare the strengths and weaknesses of
      IPTW and GPS for causal inference in three simulation studies and two real data
      sets. Again, in simulation, the GPS appears to produce estimators with lower MSE.

PMID- 21969999
TI  - Impact of outcome model misspecification on regression and doubly-robust inverse
      probability weighting to estimate causal effect.
AB  - Estimating treatment effects with observational data requires adjustment for
      confounding at the analysis stage. This is typically done by including the
      measured confounders along with the treatment covariate into a regression model
      for the outcome. Alternatively, it is also possible to adjust for confounding by
      taking into account the propensity of an individual to receive treatment, with
      inverse probability weighting (IPW). In the class of IPW estimators, the so
      called doubly-robust estimator also requires the specification of the outcome
      regression model, in addition to the propensity model. The aim of this paper is
      to investigate the impact of misspecification of the outcome model on the
      performances of the usual regression and doubly-robust IPW estimators for
      estimating treatment effects. We examine the performances of the estimators
      across the parameter space for different scenarios of model misspecification
      using large-sample theory. We find that for small-to-moderate sample sizes, the
      regression estimator compares favorably to the IPW doubly-robust estimator.
      Finally we argue, both conceptually and on the basis of our results, that
      treatment-confounder interactions should be included in the outcome regression
      model.

PMID- 21970000
TI  - [Advances in the research of primary biliary cirrhosis].

PMID- 21970001
TI  - [Research development of pruritus and fatigue in primary biliary cirrhosis].

PMID- 21970003
TI  - [Metabolic nuclear receptors and primary biliary cirrhosis].

PMID- 21970002
TI  - [Innate immunity and primary biliary cirrhosis].

PMID- 21970004
TI  - [Animal models of primary biliary cirrhosis].

PMID- 21970006
TI  - Abstracts of the International Review of Bipolar Disorders and Winter Workshop in
      Psychoses Conferences.

PMID- 21970005
TI  - Standing low-field magnetic resonance imaging appearance of normal collateral
      ligaments of the equine distal interphalangeal joint.
AB  - High- and low-field magnetic resonance (MR) imaging systems are available for
      clinical diagnosis of collateral desmopathy of the equine distal interphalangeal
      joint (DIJ). Knowledge of the normal appearance, size, shape,and signal variation
      of these ligaments on high- and low-field MR images is essential when assessing
      desmopathy detected by MR imaging. However, there are no descriptions of the
      normal features of DIJ collateral ligaments on images obtained with a standing
      low-field MR system. Low-field MR imaging characteristics of normal collateral
      ligaments of the DIJ of cadaver feet were corroborated with high-field MR imaging
      and histologic examination to exclude desmopathy. The size and shape of the
      collateral ligaments of the DIJ was similar among limbs; however, the signal
      pattern of the ligaments varied depending on the segment of the ligament being
      assessed and the MR sequence used. In limbs positioned within the magnet as
      recommended for clinical MR imaging, collateral ligaments of the DIJ have
      heterogeneous signal pattern with a peripheral region of increased signal
      intensity at the level of the middle phalanx that can be confused with a
      desmopathy.The MR imaging characteristics of normal collateral ligaments of the
      DIJ are related to their anatomy and fiber configuration. The results of this
      study support the presence of magic angle effect within the axial margin of the
      CL of the DIJ at the level of fiber divergence within the proximal to mid-portion
      of the ligament.

PMID- 21970007
TI  - [The discarding of hooded dresses and veils by women in Montenegro from 1947 to
      1953].

PMID- 21970008
TI  - The evolution of "Portuguese" identity: Luso-Africans on the Upper Guinea Coast
      from the sixteenth century.

PMID- 21970009
TI  - The first decade of "European beer" in apartheid South Africa: the state, the
      brewers and the drinking public, 1962-72.

PMID- 21970010
TI  - The pragmatics and politics of Aboriginal tradition and identity in Australia.

PMID- 21970011
TI  - The quality of liquor in Nigeria during the colonial era.

PMID- 21970012
TI  - [The issue of the entrance of foreign women in treaty ports before and after the
      Opium War].

PMID- 21970013
TI  - "Worries of the heart": widowed mothers, daughters and masculinities in Maragoli,
      western Kenya, 1940-60.

PMID- 21970014
TI  - A poisoning of no substance: the trials of medico-legal proof in    mid-Victorian
      England.

PMID- 21970015
TI  - Bagdadi Jewish merchants in Shanghai and the Opium trade.

PMID- 21970016
TI  - Coolie or worker? Crossing the lines in colonial Java, 1780-1942.

PMID- 21970017
TI  - Embroidering the Past: phulkari textiles and gendered work as    'tradition' and
      'heritage' in colonial and contemporary Punjab.

PMID- 21970018
TI  - Faithful daughter, murdering mother: transgression and social control in colonial
      Namibia.

PMID- 21970019
TI  - [Cultural fractures and fragmented identities: confrontation with    traditional
      culture in postcolonial Maori society].

PMID- 21970020
TI  - Guarding Beijing's food security in the Qing Dynasty: state, market, and police.

PMID- 21970021
TI  - The Freudian subject and the Maoist mind: the diaries of Hermine Hug-Hellmuth and
      Lei Feng.
AB  - Although written in vastly different cultural contexts and periods, Hermine Hug
      Hellmuth's "Diary of a Young Girl" (1919) and Lei Feng's "The Diary of Lei Feng"
      (1963) both to a large extent were written as concept pieces, with the goal of
      illustrating specific theories of the self. In the case of Hug-Hellmuth, the
      underlying theory is the Freudian sexualized unconscious mind, whereas for Lei
      Feng, it is Maoist revolutionary optimism. Additionally, both diaries have
      unusually strong inauthentic or 'fake' aspects. Although Hug-Hellmuth never
      admitted to writing the diary, most critics believed it came from her pen. Lei
      Feng's diary was revised through his own attempts to present himself as
      politically progressive, by editors, and through successive political movements
      that focused on the person behind the diary and made him one of the most widely
      recognized figures in China. As such, the diaries are excellent windows into
      powerful and long-lasting ideological constructs.

PMID- 21970022
TI  - Comment on 'Radiation induced cancer arises from a somatic mutation'.

PMID- 21970023
TI  - Reply to comment on 'Radiation induced cancer arises from a somatic mutation'.

PMID- 21970024
TI  - Jose Bleger: Jew, Marxist and psychoanalyst.
AB  - The article analyses the trajectory of Dr. Jose Bleger (1922-1972), an Argentine
      psychoanalyst who tried to articulate his triple identity as a Jew, a Marxist,
      and a psychoanalyst. Bleger played a central role in the constitution of the 'psy
      movement' and, in more general terms, in the diffusion of a 'psy culture' in
      Argentina, a country that today is considered as one of the 'world capitals of
      psychoanalysis'. However, his trajectory showed not only the limits of his
      projects in the increasingly politically polarized Argentina of the 1960s, as
      well as their internal contradictions, but also the difficulties of articulating
      different identities in those agitated times. Through an analysis of Bleger's
      trajectory this article explores larger issues of Argentine political culture and
      their relations with the emergence of a psychoanalytic culture.

PMID- 21970025
TI  - Freud's Mexican readers.
AB  - This essay presents an overview of artists and writers who read Freud's work in
      Mexico between 1920 and 1968. The focus is on cultural readings of Freud: non
      clinical interpretations of psychoanalysis that applied Freud's theory to
      literary, artistic, philosophical, or religious questions. The essay focuses on
      Salvador Novo, one of the poets associated with the Contemporaneos group, and his
      reading of the "Three Essays in the Theory of Sexuality;" Raul Carranca y
      Trujillo, a judge and criminologist who used psychoanalysis in his work,
      including the trial of Trotky's assassin; Octavio Paz, a poet and intellectual
      who wrote an essay on Mexican history, "The Labyrinth of Solitude," as a response
      to "Moses and Monotheism;" and Gregorio Lemercier, a Benedictine monk who placed
      his monastery in group analysis. These unorthodox readings of Freud opened the
      door for some of the most daring intellectual experiments in the 20th century.

PMID- 21970026
TI  - Abstracts of the SAHM (Society for Adolescent Health and Medicine) 2011 Annual
      Meeting. March 29-April 1, 2011. Seattle, Washington, USA.

PMID- 21970027
TI  - Le melting-pot: made in America, produced in France.

PMID- 21970028
TI  - Abstracts of the 2011 Asian-Pacific HPBA (Hepato-Pancreato-Biliary Association)
      3rd Biennial Congress. September 27-30, 2011. Melbourne, Australia.

PMID- 21970029
TI  - Regulatory T cells: Pursuing a germinal centre career.

PMID- 21970030
TI  - Individual and small-group market health insurance rate review and disclosure:
      state and federal roles after PPACA.
AB  - Oversight of private insurance, including health insurance, is primarily a state
      responsibility. Each state establishes its own laws and regulations regarding
      insurer activities, including premium increases for the insurance products within
      its purview. The authority that state regulators have to review and deny requests
      for premium changes varies from state to state, as do the amount of resources
      available to state insurance departments for reviewing premium changes. In some
      markets where insurers have proposed or implemented steep increases, such changes
      have received considerable attention from the press, state regulators, and
      policymakers. The Patient Protection and Affordable Care Act (PPACA) requires
      annual review of premium increases and disclosure of those increases determined
      unreasonable beginning in September 2011. Under PPACA, each state will conduct
      these reviews for individual and small-group health insurance unless the federal
      government concludes they do not have an effective review program and assumes
      review responsibility. As they did prior to PPACA, state laws govern whether
      rates go into effect and establish the parameters of regulators' authority. This
      issue brief outlines specific state and federal roles in the rate review process
      and changes to rate review processes since PPACA was enacted.

PMID- 21970031
TI  - Editors' note concerning a development of database analysis by Smith and Stein
      (2009).

PMID- 21970032
TI  - Postcolonial Freud: psychoanalysis in the French Antilles.
AB  - While Martinique and Guadeloupe were assimilated into the French state in 1946,
      traces of colonial power relations and economic structures persist despite the
      islands' current status as French 'departements' equal to any other. This article
      examines the contributions of Freud's thought to the shift in critical
      perspective that has allowed the continued "colonial" status of these islands,
      and the cultural alienation of its people, to be identified as a problem or
      phenomenon requiring analysis and rectification. Speaking of "postcolonial Freud"
      in this context is tantamount to asking: which postcolony for the French
      Antillean future, and which Freud for the thought emerging from this space?

PMID- 21970033
TI  - Stockpiling supplies for the next influenza pandemic.
AB  - Faced with increasing concerns about the likelihood of an influenza pandemic,
      healthcare systems have been challenged to determine what specific medical
      supplies that should be procured and stockpiled as a component of preparedness.
      Despite publication of numerous pandemic planning recommendations, little or no
      specific guidance about the types of items and quantities of supplies needed has
      been available. The primary purpose of this report is to detail the approach of 1
      healthcare system in building a cache of supplies to be used for patient care
      during the next influenza pandemic. These concepts may help guide the actions of
      other healthcare systems.

PMID- 21970034
TI  - Fixing Freud: the Oedipus complex in early twenty-first century US American
      novels.
AB  - Representations of Sigmund Freud in early 21st century US American novels rely on
      and respond to the image of Freud that emerged from investigations by Paul Roazen
      ("Brother Animal," 1969) and Jeffrey Moussaieff Masson ("The Assault on Truth,"
      1984), which cast doubt on the validity of the Oedipus complex. Relying on
      Roazen, Brenda Webster's "Vienna Triangle" (2009) links Freud's oedipal thinking
      to paranoia and male masochism. Working with Masson, Selden Edwards's "The Little
      Book" (2008) takes Freud to task for abandoning the seduction theory in favor of
      the Oedipus complex. Jed Rubenfeld's "The Interpretation of Murder" (2006)
      rethinks the Oedipus complex as a projection of adults onto their children. All
      three novels seek to celebrate Freud's understanding of the human psyche, while
      shifting the focus of the oedipal structure away from the murderous and lustful
      child toward the adult.

PMID- 21970035
TI  - [The banishment of the marvellous. Hermaphrodites and sexual mutants in
      Enlightenment Spain].
AB  - This article presents a historical synthesis in order to trace how the collective
      belief in the existence of hermaphrodites and sex-changes was slowly eroded in
      the changing medical and cultural context of Enlightenment Spain. In order to
      explain this change, three interlinked processes are outlined. First, the
      naturalization of the monster and the disappearance of the "marvellous" in
      Enlightenment science. Second, the consolidation of modern legal or forensic
      science and the rise of the medical specialist as the relevant authority in the
      determination of sexual identity. Third, the emergence of the notion of
      fundamental biological differences between the sexes. The article concludes by
      discussing the consequences of these shifts for early nineteenth-century Spanish
      medicine.

PMID- 21970036
TI  - [The cascade scheme as a methodical platform for analysis of health risks in
      space flight and partially and fully analog conditions].
AB  - Space anthropoecology, a subsection of human ecology, studies various aspects of
      physiological, psychological, social and professional adaptation to the extreme
      environment of space flight and human life and work in partially- and fully
      analogous conditions on Earth. Both SF and simulated extreme conditions are known
      for high human safety standards and a substantial analytic base that secures on
      line analysis of torrent of information. Management evaluation and response to
      germing undesired developments aimed to curb their impact on the functioning of
      the crew-vehicle-environment system and human health involve the complete wealth
      of knowledge about risks to human health and performance. Spacecrew safety issues
      are tackled by experts of many specialties which emphasizes the importance of
      integral methodical approaches to risk estimation and mitigation, setting up
      barriers to adverse trends in human physiology and psychology in challenging
      conditions, and minimization of delayed effects on professional longevity and
      disorders in behavioral reactions.

PMID- 21970037
TI  - [Correction of the functional state of deck aviation pilots by the course of
      inhalation of therapeutic doses of xenon during long march].
AB  - The article deals with efficiency of the course of O2-Xe inhalation for
      correction of the functional state of deck aviation pilots in a long march. The
      course was shown to stabilize vagosympathetic balance in organism, to compensate
      functioning and to retain reserve of the cardiovascular system that resulted in
      significant psychoemotional animation attested by self-appreciation, amelioration
      and cheerfulness, and weakening of reactive anxiety. These observations point to
      applicability of xenon-based gas mixtures to correction of the pilot's functional
      state in the most intensive periods of service. Guidelines for broad adoption of
      the method by military medicine have been developed.

PMID- 21970038
TI  - [Characteristics of local human skeleton reactions to microgravity and drug
      treatment of osteoporosis in clinic].
AB  - Analysis of the results of long-term investigations of bones in cosmonauts flown
      on the orbital station MIR and International space station (n = 80) was
      performed. Theoretically predicted (evolutionary predefined) change in mass of
      different skeleton bones was found to correlate (r = 0.904) with position
      relatively the Earth's gravity vector. Vector dependence of bone loss ensues from
      local specificity of expression of bone metabolism genes which reflects mechanic
      prehistory of skeleton structures in the evolution of Homo erectus. Genetic
      polymorphism is accountable for high individual variability of bone loss attested
      by the dependence of bone loss rate on polymorphism of certain bone metabolism
      markers. Parameters of one and the other orbital vehicle did not modulate
      individual-specific stability of the bone loss ratio in different segments of the
      skeleton. This fact is considered as a phenotype fingerprint of local metabolism
      in the form of a locus-unique spatial structure of distribution of noncollagenous
      proteins responsible for position regulation of endosteal metabolism. Drug
      treatment of osteoporosis (n = 107) evidences that recovery rate depends on bone
      location; the most likely reason is different effectiveness of local osteotrophic
      intervention into areas of bustling resorption.

PMID- 21970039
TI  - [Spatial distribution of local absorbed doses inside the Russian segment of the
      International Space Station].
AB  - The article discusses the procedure of operational radiation safety monitoring
      with the use of portable Pille-MKS dosimeters, presents the results of ISS dose
      measurements from September 22, 2003 (after Pille deployment on board the ISS) to
      March 16, 2011 (completion of the ISS-25 mission). The necessity of continuous
      dynamic tracking of the radiation environment in ISS compartments arises from the
      character and uniqueness of space ionizing radiation effects on crew. Radiation
      loading in the ISS compartments was analyzed and results of using different
      dosimeters were compared. Experimental radiation studies of the ISS piloted
      compartments are needed for reliable prediction of doses for the crew that still
      defy precise estimation.

PMID- 21970040
TI  - [Metabolic effects of physical countermeasures against deficient weight-bearing
      in an experiment with 7-day immersion].
AB  - Metabolic effects of physical countermeasures against deficient weight-loading
      were studied in three groups of 21-30 y.o. volunteers for 7-d dry immersion.
      Blood serum was investigated for 38 biochemical parameters that characterize
      myocardium, skeletal musculature, hepatobiliary system, kidney, pancreas, GI
      tract, prostate, and protein-nucleic, carbohydrate, electrolyte and mineral
      metabolism. Seven-day DI w/o countermeasures (n = 5) increased concentration of
      conjugated bilirubin, suppressed activities of muscular (creatine phosphokinase
      MM) and myocardial enzymes (CPK MB, OBDH), and caused an upward trend in
      cholesterol, its atherogenic LDP fraction and triglycerides. Mechanic sole
      stimulation (n = 6) intensified, within the physiological norm, erythrocyte
      hematolysis raising total bilirubin and potassium. Despite the stimulation,
      activity of muscle and myocardial enzymes made a decrease. Blood creatinine
      decreased to a less extent than in the immersed group w/o stimulation, however,
      lipid parameters did not rise. High-frequency stimulation of the lower leg and
      hip muscles in the course of immersion (n = 5) was noted to heighten the activity
      of muscle enzymes and potassium level in blood beyond the physiological norm.
      Change in creatinine did not reach a statistical significance and lipid
      metabolism parameters were not different from baseline values. Application of
      these physical methods of counteracting deficiency of weight bearing did not
      interfere with redistribution of body liquids due to immersion. Values of the
      parameters under study were mostly within the normal limits throughout the
      experimental exposure suggesting absence of pathological developments during DI
      or in consequence of physical stimulation. Therefore, the reactions were
      obviously of normal adaptive character.

PMID- 21970041
TI  - [Change in sensitivity of the central respiration mechanism in the 21-hour
      bedrest conditions].
AB  - The investigation was aimed at studying the mechanisms for change in the
      respiration center sensitivity in consequence of 21-hr bed rest with head-end
      tilted at -15 degrees combined with liquid loss (lasix, 20 ml) and recovery (IV
      infucol and glucose). Time of maximal breath-holding, capillary and venous O2 and
      CO2 pressure values were measured in the baseline data collection period, during
      and shortly after BR. Data analysis showed that extension of the maximal breath
      holding time both during inspiration and expiration was statistically significant
      in the initial 10 minutes of tilting. Comparison of the breath-holding test data
      between the experimental series demonstrated that infusion of equally glucose and
      infucol did not affect voluntary apnea during inspiration or expiration. From BR
      hour 17, partial pressure of venous O2 showed a significant rise, while venous
      CO2 pressure decreased, also significantly. It is hypothesized that degradation
      of the respiration center sensitivity was connected most likely with blood
      pooling in the upper body and altered pressure on the baroreceptors.

PMID- 21970042
TI  - [Expression of cytoskeleton genes in culture of human mesenchymal stromal cells
      in different periods of simulating the effects of microgravity].
AB  - Simulation of microgravity for cultivated multipotent mesenchymal stromal cells
      (MSCs) from human marrow changes transiently expression of genes associated with
      actin cytoskeleton; the effect fades away partially in 120 hrs. following
      microgravity and completely after 24-hr cell readaptation to static conditions.
      These changes in expression of some cytoskeleton genes seem to predetermine their
      reaction to simulated microgravity, and therefore inhibition of MSCs
      differentiation potential.

PMID- 21970043
TI  - [Effect of 24-hour sleep deprivation on the oculomotor reactions of human
      operator].
AB  - The article presents the results of oculomotor reaction investigations during 24
      hour sleep deprivation of 10 normal male subjects aged 25 to 30 yrs. Video
      nistagmograph VNG System VO-25 was used for binocular registration of eye
      movements. The proposed video procedures for assessment of the functional ability
      of human operator are a balancing test, investigation of saccadic and smooth
      tracking eye movements. The balancing test is designed to determine the nystagmic
      activity, the saccade test, latency, peak velocity and precision of saccades, and
      the smooth tracking test, standard errors in tracking velocity and displacement
      In addition to video oculography, velocity of a simple sensorimotor reaction was
      measured and the self-rating scale of well-being, alertness and mood (SAN) was
      employed. The balancing test showed balancing nystagmus; occurrence of this
      nystagmus grew high with desynchronosis. Saccades registered during sleep
      deprivation pointed to a considerable decline of velocity, less noticeable
      extension of latency and degradation of precision. Sleep deprivation reduced
      values of the mean coefficient of gain and increased the standard error in
      velocity and displacement of smooth eye tracking.

PMID- 21970044
TI  - [Theoretical analysis of recompression-based therapies of decompression illness].
AB  - Theoretical analysis is concerned with the benefits of oxygen, air and nitrogen
      helium-oxygen recompression schedules used to treat decompression illness in
      divers. Mathematical modeling of tissue bubbles dynamics during diving shows that
      one-hour oxygen recompression to 200 kPa does not diminish essentially the size
      of bubble enclosed in a layer that reduces tenfold the intensity of gas diffusion
      from bubbles. However, these bubbles dissolve fully in all the body tissues
      equally after 2-hr. air compression to 800 kPa and ensuing 2-d decompression by
      the Russian navy tables, and 1.5-hr. N-He-O2 compression to this pressure
      followed by 5-day decompression. The overriding advantage of the gas mixture
      recompression is that it obviates the narcotic action of nitrogen at the peak of
      chamber pressure and does not create dangerous tissue supersaturation and
      conditions for emergence of large bubbles at the end of decompression.

PMID- 21970045
TI  - [Evaluation of potentiality of combined SHF- and glow discharge in
      intensification of carbon dioxide and hydrogen processing within life support
      system].
AB  - The article reports an experimental carbon dioxide hydration process in combined
      SHF- and glow discharge, and describes a design of SHF plasmatrones for CO2
      processing at air pressure and in an integrated unit. Maximal transformation of
      80% CO2 per a run was reached with the total input power of no more than 0.9 kW.
      Thermal zero lag of plasma forming, essentially instant and timely engagement and
      disengagement of thermal action on CO2-H2 mixture renders SHF-energy applicable
      to intensification of next generation life support technologies, processing of
      these gases within atmosphere regeneration system specifically.

PMID- 21970046
TI  - [System of therapy and prophylaxis of hard tooth tissues pathology in the group
      of pilots].
AB  - Survey of 77 males aged 22 to 55 including 43 pilots (main group), 24 non-flying
      employees (comparison group) and 10 essentially healthy men with sanitized oral
      cavity (control group) revealed caries in 100% members of groups 1 and 2.
      Prevalence of other than caries pathologies was higher in the group of pilots.
      Analysis of mixed unstimulated saliva showed calcium and phosphates reduction by
      half in 50% and 30% of pilots, respectively. Investigation of hair elemental
      composition displayed also deficiency of Ca and P in pilots. The authors
      recommend methods for dental rehabilitation as an indispensable part of medical
      care for flying personnel.

PMID- 21970047
TI  - [Characteristics of endothelium hemodynamics and functional condition of
      hypertensive patients in high mountains].
AB  - Hemodynamics, geometry of the left myocardium ventricle (LV), blood nitrogen
      oxide and their interdependence were studied in hypertensive (n = 90) and normal
      mountain dwellers (n = 40) at the age of 37 to 72 years. The patients underwent
      general clinical and outpatient examination, electro- and echocardiography. The
      hypertensive patients were diagnosed for disorders in endothelium functioning,
      intracardiac hemodynamics, and LV geometry. In patients with class II and II
      hypertension, LV volumetric parameters were enlarged and contractility parameters
      decreased by 29%. Also, indices of LV mass, relative wall thickness and
      sphericity in these patients were significantly higher as compared with normal
      people. Blood concentration of nitrogen oxide was reduced by 28% and 40% in
      patients with hypertension class II and III, respectively. This reduction was
      caused disbalance of NO plasma metabolites and erythrocytes. All together data
      from the groups of equally patients and normal people suggests a particular role
      of nitrogen oxide in controlling myocardium LV hemodynamics and geometry in
      hypertensive mountain dwellers.

PMID- 21970049
TI  - Preserving life and facilitating death: what role for government after Haas v.
      Switzerland?

PMID- 21970048
TI  - [Dynamic modeling of living systems--structures with stable disbalance
      conditions].

PMID- 21970050
TI  - Forwards or backwards? New directions in Danish patients' rights legislation.
AB  - The Danish Patients' Rights Act from 1998 was the first comprehensive piece of
      legislation addressing the basic legal values and principles governing the
      relation between patient and the health care services. Since the adoption of the
      Act there has been continuous legislative activity in the field, and the
      objective of the article is to discuss how recent developments in Danish
      patients' rights legislation shall be interpreted in terms of balancing interests
      of patients towards interests of society and the health care professions.

PMID- 21970051
TI  - "Braxton Hick's" or the birth of a new era? Tracing the development of Ireland's
      abortion laws in respect of European Court of Human Rights Jurisprudence.
AB  - In Ireland, Article 40.3.3 degrees of Bunreacht na hEireann (the Irish
      Constitution) guarantees the right to life of the unborn child and the equal
      right to life of the mother. Abortion in Ireland is permissible only where there
      is a real and substantial risk to the mother's own life. Since Ireland became a
      signatory to the European Convention on Human Rights in 1950,2 there have been
      concerns that it could result in Ireland being compelled to introduce a right to
      abortion. This article commences with a review of the extant law on abortion in
      Ireland, tracing the Constitutional protection afforded to the unborn child. The
      article will discuss the impact of the European Court of Human Rights'
      jurisprudence in regard to access to abortion and to information on abortion
      services in Ireland in an effort to ascertain if it really has resulted in a
      radical change to Irish abortion laws. As such, it will also be necessary to
      examine the more recent decisions of the ECtHR such as Tysiac v. Poland, and A,
      B, and C v. Ireland, to determine both the approach of the ECtHR to access to
      abortion in general and also to consider if it has resulted in a liberalisation
      of abortion law in Ireland.

PMID- 21970052
TI  - The new regulation of abortion in Spain.
AB  - The enactment of Law 2/2010 on Sexual and Reproductive Health and on Voluntary
      Interruption of Pregnancy represents a radical change in the regulation of
      abortion in Spain. The law moves from the medical indication model that has been
      in place since 1985 (which established certain cases in which abortion was legal)
      towards a time-limit model that, with some exceptions, allows free abortion
      during the first 14 weeks of pregnancy. Along with the hot debate that this
      fundamental change has caused, other features of the law have also arisen as a
      source of conflict, including the regulation of the informed consent of underage
      women for having an abortion and the rules regarding the conscientious objection
      by healthcare professionals.

PMID- 21970053
TI  - Monitoring quality in a federal state with shared powers in healthcare: the case
      of Belgium.
AB  - The Belgian healthcare system consists of a complex of more or less autonomous
      groups of healthcare providers. It is the responsibility of the government to
      ensure that the fundamental right to qualitative healthcare is secured through
      the services they provide. In Belgium, the regulatory powers in healthcare are
      divided between the federal state and the three communities. Both levels, within
      their area of competence, monitor the quality of healthcare services. Unique to
      the Belgian healthcare system is that the government that providers are
      accountable to is not always the same as the government that is competent to set
      the criteria. The goal of this article is to provide an overview of the main
      mechanisms that are used by the federal government and the government of the
      Flemish community to monitor healthcare quality in hospitals. The Flemish
      community is Belgian's largest community (6.2 million inhabitants). The overview
      is followed by a critical analysis of the dual system of quality monitoring.

PMID- 21970054
TI  - ECHR 2011/14 Case of Kiyutin v. Russia, 10 March 2011, no. 2700/10 (First
      Section).

PMID- 21970055
TI  - ECHR 2011/15 Case of R.R. v. Poland, 26 May 2011, no. 27617/04 (Fourth Section).

PMID- 21970056
TI  - ECHR 2011/16 case of Tupa v. The Czech Republic, 26 May 2011, no. 39822/07.

PMID- 21970057
TI  - ECHR 2011/17 Case of Hadzic and Suljic v. Bosnia and Herzegovina, 7 June 2011,
      no. 39446/06 and 33849/08 (Fourth Section).

PMID- 21970059
TI  - ECJ 2011/9, MSD Sharp 7 Dohme GmbH v. Merckle GmbH, 5 May 2011 (case C-316/09).

PMID- 21970058
TI  - ECJ 2011/ 8 Novo Nordisk AS v. Ravimiamet, 5 May 2011 (C-249/09).

PMID- 21970060
TI  - [Studies of prevalence in surveillance of hospital-acquired infections].

PMID- 21970061
TI  - Vocal therapy with larynx compression after partial laryngectomy.
AB  - The aim of the study was to establish the effects of the vocal therapy by manual
      compression of the larynx on dysphonia due to a partial laryngectomy and compare
      them with the effects of the standard vocal therapy. The prospective study
      included 66 patients submitted to any partial laryngectomy type. The patients
      were randomly classified into two groups: Group I (33) receiving the standard
      vocal therapy, and Group II (33) submitted to larynx compression vocal therapy.
      The 6-week vocal treatment was performed. The treatment effects were evaluated by
      subjective and objective voice analysis methods. The subjective and objective
      acoustic voice analysis revealed a significant influence (p < 0.05) of either of
      the two vocal therapy modes on initial dysphonia. The larynx compression vocal
      therapy had better effects on the acoustic parameters: habitual fundamental
      frequency, mean fundamental frequency, standard deviation of fundamental
      frequency, maximal fundamental frequency, harmonics-to-noise ratio, and signal-to
      noise ratio.

PMID- 21970062
TI  - [The values of serum cytokines in chronic lung disease in newborn].
AB  - INTRODUCTION: Chronic lung disease in the newborn is a complication of mechanical
      ventilation. The diagnosis of chronic lung disease is made in children of over 36
      post-conceptual weeks' age who still require additional oxygen and who have
      abnormal chest x-ray findings. This study was aimed at triaging newborns at risk
      of developing chronic lung disease. The operating study hypothesis was that the
      values of insulin-like growth factor I below 30 microg/L in the 33rd post
      conceptual week were associated with the development of chronic lung disease.
      MATERIAL AND METHODS: The above hypothesis was verified by a cohort, prospective
      study, which included preterm newborns of 33 gestational weeks' age or less who
      were hospitalised at the Department of Neonatology of the Clinical Centre of
      Montenegro from Aril 2008 to July 2009. The blood sample was taken in the 33rd
      post-conceptual week and the insulin-like growth factor value was determined by
      the method of enzyme immunoassay. RESULTS: Our study results confirmed the theory
      of statistically significant correlation of the length of pregnancy and birth
      body weight with insulin-like growth factor serum level. DISCUSSION: We did not
      find any statistically significant correlation between the insulin-like growth
      factor serum value and chronic lung disease in the newborn. It is possible that
      the insulin-like growth factor has a different role at various stages of
      pathogenesis of diseases of prematurity. CONCLUSION: We believe that by
      correcting the term for determining the levels we can get a significant
      correlation between low values of insulin-like growth factor -1 and chronic lung
      disease.

PMID- 21970063
TI  - [Comparison of efficiency and toxicity of two chemotherapy protocols in treatment
      of advanced non-small cell lung cancer].
AB  - INTRODUCTION: This study was aimed at comparing the efficiency and tolerability
      of two reference protocols Cisplatin and Etoposide and Cisplatin and Vinorelbine
      in advanced Non-Small Cell Lung Cancer. MATERIAL AND METHODS: A total of 60
      patients (two groups consisting of 30 patients) were treated for advanced Non
      Small Cell Lung Cancer during the period from January to December 2005 according
      to the reference protocols (Cisplatin 100 mg/m2 D1; Vinorelbine 30 mg/m2 D1, D8
      on 4 weeks) and (Cisplatin 100 mg/m D1; Etoposide 100 mg/m2 D1, D3, D5 on 4
      weeks) at the Department of Oncology of KBC "Bezanijska kosa". All patients were
      analysed for tumour response, progression free survival as well as for toxicity.
      X2 test, Kaplan Meiers curves and Log rank test were used for statistical
      analysis. RESULTS: Although the recorded response rates were a bit lower than in
      previously published trials, they were not significantly different p = 0.485. No
      statistically significant difference was recorded in either progression free
      survival or overall survival. The chemotherapeutical Cisplatin/Etoposide protocol
      proved to be more toxic both in hematologic (3% vs. 10%) and total toxicities (p
      = 0.047). CONCLUSION: Our study proved both protocols to have equivalent
      efficacy. However, the Cisplatin, Vinorelbine protocol could be recommended
      because of its less expressed toxic effects.

PMID- 21970064
TI  - Anxiety sensitivity in adolescents with somatoform autonomic dysfunction and
      adolescents with insulin dependent diabetes mellitus.
AB  - Anxiety sensitivity is defined as a belief that anxiety or fear may cause
      illness, embarrassment, or additional anxiety. The main purpose of this study was
      to find out if there were differences among adolescents with insulin dependent
      diabetes mellitus, adolescents with somatoform autonomic dysfunction and their
      healthy peers in different aspects of psychological functioning and anxiety
      sensitivity. The sample consisted of 93 subjects, aged 12 to 16. Hamburg
      Neuroticism and Extraversion Scale, Child Behaviour Checklist and Childhood
      Anxiety Sensitivity Index were administrated. The adolescents with somatoform
      autonomic dysfunction had significantly higher scores on neuroticism scale,
      different Child Behaviour Checklist subscales, and on anxiety sensitivity. Both
      groups with diagnosed illness had lower scores on extraversion scale compared to
      healthy peers. This study has shown that the adolescents with somatoform
      autonomic dysfunction are more prone to fears regarding bodily functioning, and
      that they are at a higher risk of developing an anxiety disorder.

PMID- 21970065
TI  - Thiobarbituric acid reactive substances as marker of oxidative stress in
      pregnancies with pre-eclampsia.
AB  - Pre-eclampsia is characterized by increased lipid peroxidation and diminished
      antioxidant capacity. The aim of the study was to establish concentration of
      thiobarbituric acid reactive substances as a marker of lipid peroxidation in
      normal pregnancies and in pregnancies complicated with pre-eclampsia, and to
      estimate the possibility of using thiobarbituric acid reactive substances as a
      screening method for development of pre-eclampsia. The study was conducted at the
      Department of Obstetrics and Gynaecology, Clinical Centre of Vojvodina. The study
      included 57 singleton pregnancies, gestation > or = 24 weeks, of which 29 were
      healthy pregnancies and 28 were with pre-eclampsia, defined as systolic arterial
      pressure of > or = 90 mmHg, diastolic of > or = 145 mmHg, and 24h proteinuria of
      > or = 300 mg. Thiobarbituric acid reactive substances concentrations evaluated
      by malondialdehyde equivalent standards (OxiSelect TBARS Assay Kit
      (malondialdehyde Quantitation), Cell Biolabs' OxiSelect) showed that oxidative
      stress was more evident in the group with pre-eclampsia, though not statistically
      significant (p = 0.107). There was no correlation ofthiobarbituric acid reactive
      substance levels with gestation in either group. The differences between the
      level of thiobarbituric acid reactive substance concentrations in pre-eclampsia
      and healthy pregnancies indicate the possibility of using thiobarbituric acid
      reactive substances as a screening tool for the development of pre-eclampsia.
      Further studies with larger numbers of patients are needed in order to come to
      final conclusions.

PMID- 21970066
TI  - [Juvenile myoclonic epilepsy: under-diagnosed syndrome].
AB  - INTRODUCTION: Juvenile myoclonic epilepsy is an idiopathic, hereditary form of
      epilepsy. Although juvenile myoclonic epilepsy is a well defined clinical
      syndrome, attempts at diagnosing it commonly fail. ETIOPATHOGENESIS: The exact
      cause of juvenile myoclonic epilepsy remains unknown. Clinical, morphological and
      metabolic data suggest a preferential role for frontal regions in this syndrome.
      Several major genes for juvenile myoclonic epilepsy have been identified, but
      these genes account for only a small proportions of juvenile myoclonic epilepsy
      cases, suggesting multifactorial or complex inheritance in most. CLINICAL
      MANIFESTATIONS: Juvenile myoclonic epilepsy is characterized by the triad of
      myoclonic jerks on awakening (all patients), generalized tonic-clonic seizures (>
      90% of patients) and typical absences (about one third of patients). Seizures
      have an age-related onset, circadian distribution and are frequently precipitated
      by sleep deprivation, fatigue and alcohol intake. Intelligence is normal.
      DIAGNOSIS: Juvenile myoclonic epilepsy diagnosis is based upon clinical criteria
      and typical electroencephalographic findings (generalized pattern of spikes
      and/or polyspikes and waves). All other tests are normal. TREATMENT AND
      PROGNOSIS: Both medical treatment and counselling are important in the management
      of juvenile myoclonic epilepsy. Mono-therapy with valproate is the preferred
      treatment. Some of the newer antiepileptic drugs have been suggested as possible
      alternatives. Juvenile myoclonic epilepsy has a good prognosis. Lifelong
      treatment is usually considered necessary in vast majority of patients due to the
      increased risk of relapse if treatment is discontinued. CONCLUSION: Juvenile
      myoclonic epilepsy is a common, although under-diagnosed epileptic syndrome. The
      clinician should study the occurrence of myoclonic jerks and should consider
      atypical presentations.

PMID- 21970067
TI  - [Resistance of nerve cells to oxidative injury].
AB  - INTRODUCTION: Reactive oxygen species are particularly active in the brain and
      neuronal tissue, and they are involved in numerous cellular functions, including
      cell death and survival. BRAIN AND OXIDATIVE STRESS: A high metabolic rate and an
      abundant supply of the transition metals make the brain an ideal target for a
      free radical attack. In addition, the brain has a high susceptibility to
      oxidative stress due to the high lipid content and relatively lower regenerative
      capacity in comparison with other tissues. VULNERABILITY OF NERVE CELLS TO
      OXIDATIVE STRESS: The neurons are more vulnerable to oxidative stress than other
      brain cell types. In addition to the two conventional enzymes, catalase and
      glutathione peroxidase, peroxiredoxins remove intracellular hydrogen peroxide by
      reducing it to water. The recent work increasingly supports the hypothesis that
      peroxiredoxins are not only antioxidant proteins, but they also play a role in
      cell signaling by controlling hydrogen peroxide and alkyl hydroperoxide levels.
      The accumulating evidence demonstrates that microglia can become deleterious and
      damage neurons. The overactivated microglia release reactive oxygen species that
      cause neuronal damage in neurodegenerative diseases. CONCLUSION: The defense of
      nerve cells against reactive oxygen species--mediated oxidative damage is
      essential for maintaining the functionality of nerve cells. The ongoing studies
      show that neuron-glial compartmentalization of antioxidants is critical for the
      neuronal signaling by hydrogen peroxide as well as the neuronal protection.

PMID- 21970068
TI  - [Diagnosis and outcome of cervical artery dissection].
AB  - INTRODUCTION: Spontaneous dissection of the cervical artery is a rare non
      atherosclerotic vascular disease of unknown aetiology and unclear pathogenesis
      that may be a cause of ischemic stroke in young adults. DIAGNOSIS: Precise
      diagnosis of dissection of the cervical artery--carotid or vertebral--is possible
      with cervical axial magnetic resonance imaging and magnetic resonance
      angiography. TREATMENT: The recommended treatment in the acute phase of cervical
      artery dissection is anticoagulant or antithrombotic therapy, aimed at preventing
      a primary or recurrent ischemic event. There have been as yet no results of
      randomized controlled studies comparing efficacy of both treatments. An ongoing
      randomized multicentre study is expected to provide answers about the effects of
      these treatments in cervical artery dissection. OUTCOME: Complete resolution of
      arterial abnormalities is achieved in around 46% of stenoses. 33% of occlusions,
      and 12% of dissecting aneurysms. RECURRENT EVENTS: Recurrence of cerebral
      ischemia and cervical artery dissection seems to be rare, although some data
      suggest that early ischemic and late cervical artery dissection recurrences could
      be underestimated. MORTALITY AND FUNCTIONAL OUTCOME: In comparison with other
      causes of stroke in young adults, the functional outcome of cervical artery
      dissection is good in contrast to its socio-professional effects, which may be
      unsatisfactory. The mortality rate of cervical artery dissection is low, although
      it may be underestimated since some patients with malignant infarction die before
      the diagnosis is established. CONCLUSION: Further research is warranted to
      improve our understanding of the underlying pathophysiology, to assess the long
      term outcome, and ultimately to provide treatment and prevention strategies.

PMID- 21970069
TI  - Resistance of Escherichia coli from healthy donors and from food--an indicator of
      antimicrobial resistance level in the population.
AB  - Escherichia coli, being an important part of normal intestinal flora, is a
      frequent carrier of antimicrobial drug resistance markers and food is the most
      important vector of antimicrobial resistance genes between humans and animals.
      The aim of this study was to confirm the presence and frequency of resistance
      markers in Escherichia coli from intestinal flora and from food as an indicator
      of antimicrobial resistance level in the population. The experiment included 100
      fecal Escherichia coli isolates from healthy donors, 50 isolated in 2007 and 50
      in 2010, and 50 from food samples. The resistance markers were found in all
      groups of isolates. The resistance to ampicillin and cotrimoxazole was most
      commonly found. The finding of multi-drug-resistant strains and resistance to
      ciprofloxacin is important. The frequency of resistance markers was similar in
      food and feces. The results of this study show the need to introduce systematic
      monitoring of antimicrobial resistance of these bacteria.

PMID- 21970070
TI  - [The incidence and risk factors of ventilator-associated pneumonia in patients
      with severe traumatic brain injury].
AB  - INTRODUCTION: Patients with severe traumatic brain injury are at a risk of
      developing ventilator-associated pneumonia. The aim of this study was to describe
      the incidence, etiology, risk factors for development of ventilator-associated
      pneumonia and outcome in patients with severe traumatic brain injury. MATERIAL
      AND METHODS: A retrospective study was done in 72 patients with severe traumatic
      brain injury, who required mechanical ventilation for more than 48 hours.
      RESULTS: Ventilator-associated pneumonia was found in 31 of 72 (43.06%) patients
      with severe traumatic brain injury. The risk factors for ventilator-associated
      pneumonia were: prolonged mechanical ventilation (12.42 vs 4.34 days, p < 0.001),
      longer stay at intensive care unit (17 vs 5 days, p < 0.001) and chest injury
      (51.61 vs 19.51%, p < 0.009) compared to patients without ventilator-associated
      pneumonia. The mortality rate in the patients with ventilator-associated
      pneumonia was higher (38.71 vs 21.95%, p = 0.12). CONCLUSION: The development of
      ventilator-associated pneumonia in patients with severe traumatic brain injury
      led to the increased morbidity due to the prolonged mechanical ventilation,
      longer stay at intensive care unit and chest injury, but had no effect on
      mortality.

PMID- 21970071
TI  - Surgical treatment of neonatal ovarian cysts.
AB  - Medical experts are still at issue over the most suitable management of simple
      neonatal ovarian cysts exceeding 40mm and complex cysts of any size. The authors
      present surgical treatment of these cysts by classical laparotomy and
      laparoscopy. The study included 13 newborn babies surgically treated for 6 simple
      and 7 complex ovarian cysts. The diameter of the cysts ranged from 29 to 102mm.
      The age of children was from 2 days to 10 months. The open classical laparotomic
      approach was performed in 8 babies. In the laparotomy group, cystectomy was done
      in 3 infants with simple cysts. The other 5, presented with ovarian torsion,
      required salpingo-oophorectomy. Video-assisted cystectomy was the procedure for 3
      simplex and one complex cyst with torsion. Laparoscopic adnexectomy was applied
      in one case with auto-amputated cyst. Our small study demonstrates that
      laparoscopy is as safe and effective as classical laparotomy in managing neonatal
      ovarian cysts, but with better cosmetic results.

PMID- 21970072
TI  - [Correlation between rapid urease test and pathohistological gastrobiopsy finding
      with positive immunological test in detecting Helicobacter pylori infection].
AB  - INTRODUCTION: Helicobacter pylori is a bacterium that has been in the limelight
      of gastroenterologists and oncologists worldwide since its immediate effect on
      the development of gastritis, ulcer disease, mucosa-associated lymphoid tissue
      lymphoma and gastric cancer was proved. The aim of this study was to determine
      the correlation between the positive immunological test, rapid urease test and
      pathohistological finding in detecting Helicobacter pylori infection of the
      gastric mucosa. MATERIAL AND METHODS: This retrospective study included 250
      endoscopic findings of subjects having undergone endoscopy in the first half of
      2010 at the Ward of Gastroenterology, Department of Internal Diseases, Hospital
      in Senta. The endoscopy procedure was performed by Fujinon endoscopes and the
      fast urease test was done by the Cambridge Life Science set from England. The
      immunological test was carried out by the Vidas apparatus applying the Enzyme
      Linked Fluorescent Assay (ELFA) technique and the staining for the
      pathohistological analysis was done by the modified Giemsa method. RESULTS: The
      paper presents the results obtained by endoscopic examination of a group of 250
      patients performed at the Ward of Gastroenterology, Department of Internal
      Diseases, Hospital in Senta. The endoscopic findings were the first to be
      analyzed then the rapid urease test findings, which showed that 95 (38%) patients
      were positive and 155 (62%) patients were negative; whereas the immunologic test
      for Helicobacter pylori was positive in all 250 patients (100%). The histological
      test for Helicobacter-Like Organism was positive in 105 subjects (42%), whereas
      it was negative in 145 patients, that being 58% of all the cases. Sensitivity,
      specificity and predictability of the serological test and the rapid urease test
      were calculated according to the pathohistological finding as the "gold standard"
      and they were found to be: sensitivity 100% and specificity 0% for the
      serological test and sensitivity 90% and specificity 100% for the rapid urease
      test. The immunologic test was not correlated with other findings, and there was
      a high level of correlation between the rapid urease test and histological test
      (r = 0.927589261). The t-test was calculated to be 36.16513; p = 0.0001; that
      indicating that the correlation coefficient was statistically significant (p >
      0.01). DISCUSSION: The obtained results were compared with the data found in the
      available literature sources. CONCLUSION: It can be concluded that the most
      competent technique for the optimal diagnosis of Helicobacter pylori infection is
      the invasive one with the pathohistological examination of bioptates together
      with the rapid urease test.

PMID- 21970073
TI  - [Dorsal extrusion of intervertebral disc as a cause of cauda equina syndrome].
AB  - We have presented a case of rare dorsally sequestrated lumbar disc herniation
      manifesting as cauda equina syndrome. The patient was admitted to the
      Neurological Department of Canton Hospital Zenica due to urinary retention and
      weakness in both lower extremities. Magnetic resonance imaging showed a
      compressing mass located in the dorsal extradural space at the L2-L3 level. An
      extruded intervertebral disc was found intraoperatively. The decompression was
      followed by good recovery.

PMID- 21970074
TI  - [Historical and medical review of syphilis-afflicted army leaders, rulers and
      statesmen].
AB  - Syphilis has changed the course of history. It is a sexually transmitted disease
      caused by spiral-shaped bacterium, Treponema pallidum. The disease has been known
      under many names during history, and has had a prominent role in history and
      literature for the last several hundred years. Since its recognition in 15th
      century Europe as a new disease, syphilis has been the subject of great mystery
      and legends. Many believe that syphilis was brought to Europe by Columbus and his
      sailors, and, thereafter, many famous persons, such as political figures (King
      Charles VIII, Queen Mary I, Catherine the Great, Paul I, Vladimir Lenin),
      musicians and literary greats suffered from syphilis. Syphilis is a chronic,
      multistage disease with diverse and wide-ranging manifestations. Congenital
      syphilis is of particular concern, where the lack of prenatal testing and
      antibiotic treatment of infected pregnant women results in congenital infection
      of the fetus. Syphilis exists even nowadays and according to the World Health
      Organization estimates, there are 12 million new cases of syphilis occurring each
      year. While syphilis eradication seems a biologically plausible goal, the major
      political, cultural, and logistic difficulties involved make it unlikely.
      Regrettably, rather than becoming an infection of historical significance,
      syphilis continues to challenge researchers and clinicians in the era of HIV.

PMID- 21970075
TI  - [Job retention and nursing practice environment of hospital nurses in Japan
      applying the Japanese version of the Practice Environment Scale of the Nursing
      Work Index (PES-NWI)].
AB  - OBJECTIVES: The purpose of this study was to examine how the nursing practice
      environment affects job retention and the turnover rate among hospital nurses.
      The Practice Environment Scale of the Nursing Work Index (PES-NWI) was applied to
      investigate the nurse working environment from the viewpoint of hospital nurses
      in Japan. Methods A postal mail survey was conducted using the PES-NWI
      questionnaire targeting 2,211 nurses who were working at 91 wards in 5 hospitals
      situated in the Tokyo metropolitan area from February to March in 2008. In the
      questionnaire, hospital nurses were asked about characteristics such as sex, age
      and work experience as a nurse, whether they would work at the same hospital in
      the next year, the 31 items of the PES-NWI and job satisfaction. Nurse managers
      were asked to provide staff numbers to calculate the turnover rate of each ward.
      Logistic regression analyses were carried out, with "intention to retain or leave
      the workplace next year" as the dependent variable, with composite and 5 sub
      scale scores of the PES-NWI and nurse characteristics as independent variables.
      Correlation coefficients were calculated to investigate the relationship between
      nurse turnover rates and nursing practice environments. RESULTS: A total of 1,067
      full-time nurses (48.3%) from 5 hospitals responded. Almost all of them were men
      (95.9%), with an average age of 29.2 years old. They had an average of 7.0 years
      total work experience in hospitals and 5.8 years of experience at their current
      hospital. Cronbach's alpha coefficients were 0.75 for composite of the PES-NWI,
      and 0.77-0.85 for the sub-scales. All correlation coefficients between PES-NWI
      and job satisfaction were significant (P < 0.01). In the logistic regression
      analysis, a composite of PES-NWI, "Nurse Manager's Ability, Leadership, and
      Support of Nurses" and "Staffing and Resource Adequacy" among the 5 sub-scales
      correlated with the intention of nurses to stay on (P < 0.05). The means for
      turnover rate were 10.4% for nurses and 17.6% for newly hired nurses. These rates
      were significantly correlated to the composite and some sub-scales of the PES
      NWI. CONCLUSION: The working environment for nurses is important in retaining
      nurses working at hospitals. We confirmed the reliability and the validity of the
      PES-NWI scale based on the magnitude of the Cronbach's alpha coefficient and
      correlation coefficient between the PES-NWI scale and job satisfaction in this
      study.

PMID- 21970076
TI  - [Intervention effects of inclusive support in an "exercise and a nutritional
      community-based prevention program" for pre-frail elderly individuals].
AB  - OBJECTIVES: The purpose of this study was to examine intervention effects of a
      community-based prevention program for pre-frail elderly individuals by comparing
      an intervention group (exercise with nutritional care) with a control group
      (exercise without nutritional care). METHODS: The study was conducted in Y town
      and S city in Ibaraki Prefecture in Japan. The subjects comprised 161 pre-frail
      elderly individuals in the community-based prevention program, who were divided
      into two groups, the intervention group (N = 81, Y town, mean age : 76.2 +/- 5.7
      years), and the control group (N = 81, S city, mean age 76.2 +/- 4.7 years). The
      items surveyed included age, gender, activities of daily living, functional
      capacity, and dietary variety score (DVS). Functional fitness measurement items
      (grip strength, alternate step, 5-repetition sit-to-stand, one-leg balance with
      eyes open, tandem stance, functional reach (FR), sit and reach, 5-m habitual
      walk, and timed up and go (TUG)) and blood data were assessed at the beginning
      and end of the intervention. RESULTS: The DVS of the intervention group was
      significantly improved compared to that of the control group (P < 0.01). In
      particular, the food frequencies of fish and shellfish, meat, eggs, milk, fruits,
      and fat and oil (P < 0.01) were significantly increased in the intervention
      group, as were those of soybean products, seaweed, and potatoes (P < 0.05). On
      the other hand, significant increases were seen only in the frequencies of fish
      and shellfish, meat, and milk in the control group. The intervention group showed
      significant improvement in five-repetition sit-to-stand, tandem stance, FR, sit
      and reach, and TUG by the end of the intervention. In addition, the intervention
      group's performance on one-leg balance with eyes open (P < 0.05) was
      significantly improved even after adjusting for age, gender, and the functional
      fitness measurement items which were different at the beginning of the study.
      CONCLUSION: This study suggests that a combined exercise and nutrition program
      for pre-frail elderly individuals improves their food intake and functional
      fitness.

PMID- 21970077
TI  - [Factors associated with working among female physicians in Japan].
AB  - OBJECTIVES: Japan faces a very serious physician shortage and needs female
      doctors. However, a previous survey in Japan showed that female physicians were
      more likely than their male counterparts to resign from their jobs due to
      marriage and childbearing. According to studies in Western countries, the
      professional motivation of female physicians is seriously affected by sex-based
      inequalities in professional opportunities. The purpose of this study was to
      compare men and women in terms of their encounters with sex-based inequalities in
      professional opportunities and their related experiences at work, and to
      investigate factors associated with working among female physicians. METHODS: We
      sent self-administered questionnaires to 1,346 physicians who graduated from a
      private university-affiliated school of medicine in June 2009. Beginning with a
      question asking for responses to the statement, "Females are less likely to be
      promoted in medical school," the instrument included 14 questions addressing sex
      based inequalities in work opportunities; we further developed the scale using
      factor analyses. We inquired about disadvantages experienced due to sex-based
      inequalities at work by asking "Have you ever had an experience in which you were
      not able to obtain a salaried position, an opportunity for promotion, or a
      permanent position at work because of your gender?" RESULTS: Data were obtained
      from 452 men (mean age, 48 years) and 224 women (mean age, 43 years); the
      response rate was 44% for men and 71% for women. Forty women (18%) acknowledged
      encountering sex-based disadvantages, whereas only 15 men (3%) reported such
      phenomena (P < 0.001). Women had higher scores than men on all but one question
      on sex-based inequalities in work opportunities. Sixty-six percent of female
      physicians were full-time workers, 32% were part-time workers, and the remaining
      2% were unemployed. After adjusting for disadvantageous experiences, having or
      not having a child, and household income, logistic regression analyses showed
      that part-time workers were more likely than full-time workers to be married and
      to report encountering sex-based inequalities in work opportunities, whereas full
      time workers were more likely than part-time workers to have qualified as
      specialists. CONCLUSION: The data suggest that qualifying as a specialist and
      encountering sex-based inequalities in work opportunities are associated with
      working among female physicians.

PMID- 21970078
TI  - [Social support availability and psychological well-being among the socially
      isolated elderly. Differences by living arrangement and gender].
AB  - OBJECTIVES: This study aimed to clarify: a) what kind of problems isolated
      elderly tend to have in everyday life and in psychological well-being; and b) how
      these vary with living arrangement and gender, with social isolation as defined
      as low frequency of contact with people other than cohabitant family. METHODS:
      Data were extracted from the social survey for the non-institutionalized elderly
      aged 65 and over. The study population consisted of 948 individuals living alone
      and 1,426 living with others. Social isolation status was categorized into
      "having face-to-face contact", "non face-to-face contact only", and "no contact
      (i.e., isolation)" based on whether respondents had contact at least once a week
      with anyone, including kin living apart, friends and neighbors. Through logistic
      regression analyses, main and interaction effects of social isolation, living
      alone and gender were examined controlling for age, IADL and socio-economic
      status regarding the following dependent variables: Availability of informal
      support (6 items), formal support availability (2 items), depressive symptoms,
      and concerns for the future. RESULTS: Forty-two percent of males living alone
      were categorized as isolated, showing a remarkable difference from females living
      alone (17%). Odds ratios for "no contact (isolation)" to "face-to-face contact"
      were significantly larger than 1 for all dependent variables, meaning isolated
      elderly were less likely to have all types of informal support, advisors for
      public services and awareness of comprehensive support centers, were more likely
      to be depressive and have high concerns for the future. An interaction effect
      between isolation and living alone was significant for informal support, which
      suggested that the combination of these factors was more likely to lead to a
      higher risk of unavailability of informal support. Living alone showed an
      independent (main) effect on limited variables such as a few types of informal
      support and depressive symptoms. CONCLUSION: Socially isolated elderly are less
      likely to be able to receive informal/formal support and are more likely to be
      depressive and concerned about the future, whether or not they live alone or with
      family. The results showed many problems to exist in everyday life and
      psychological well-being.

PMID- 21970079
TI  - [A nationwide survey of municipalities' policy concerning the environment and
      citizen involvement].

PMID- 21970080
TI  - Medical incident analysis: effective teamwork is needed.

PMID- 21970081
TI  - Ticagrelor. Acute coronary syndromes: nothing new.
AB  - Several revascularisation methods are effective in patients with acute coronary
      syndromes. Standard antithrombotic treatment combines heparin and aspirin during
      the acute phase, followed by long-term aspirin therapy. The only proven advantage
      of adding clopidogrel is for patients who undergo angioplasty with stenting.
      Ticagrelor is an antiplatelet drug belonging to a different chemical class than
      clopidogrel. Its chemical structure resembles that of adenosine. Ticagrelor has
      been authorised in the European Union for patients with acute coronary syndromes,
      in combination with aspirin. Clinical evaluation is mainly based on a double
      blind randomised trial comparing ticagrelor + aspirin versus clopidogrel +
      aspirin in 18 624 patients who underwent angioplasty (64% of patients), coronary
      artery bypass grafting (10%), or who received medical treatment only. Half of the
      patients were treated for at least 9 months. After 12 months of treatment,
      compared to the clopidogrel group, overall mortality appeared to be significantly
      lower in the ticagrelor group (4.5% versus 5.9%), along with cardiovascular
      mortality (4.0% versus 5.1%). Symptomatic myocardial infarction was also less
      frequent (5.8% versus 6.9%), but not stroke (about 1.4% in both groups).
      Ticagrelor did not statistically significantly reduce overall mortality in
      patients who had angioplasty with stenting, but stent thrombosis was less
      frequent than with clopidogrel (2.9% versus 3.8%). In combination with aspirin,
      ticagrelor provoked more bleeding than clopidogrel, based on the definition used
      in the trial (16.1% versus 14.6%). In contrast, the rate of major bleeding was
      similar in the two groups (11.5%), including fatal bleeding (0.3%). The adverse
      effect profile of ticagrelor resembles that of adenosine in certain respects. For
      example, dyspnoea was more frequent with ticagrelor than with clopidogrel (13.8%
      versus 7.8%), as were conduction disorders and ventricular pauses at the
      beginning of treatment (5.8% versus 3.6%). There were also more cases of
      hyperuricaemia and elevated creatinine levels with ticagrelor. Ticagrelor and its
      active metabolite are substrates and inhibitors of cytochrome P450 isoenzymes and
      P-glycoprotein, creating a risk of multiple pharmacokinetic interactions.
      Pharmacodynamic interactions are also likely to occur, especially with
      antithrombotic agents and heart-rate-lowering drugs. In practice, in patients
      with an acute coronary syndrome treated with angioplasty and stenting, and who
      are also receiving aspirin, it remains to be shown whether the harm-benefit
      balance of ticagrelor is clearly better than that of clopidogrel. In other
      settings, there is no firm evidence that ticagrelor is better than aspirin alone.

PMID- 21970082
TI  - Erlotinib and maintenance therapy of non-small cell lung cancer. Inadequate
      assessment; authorisation unjustified.

PMID- 21970083
TI  - Common stem: -caine, -cain.

PMID- 21970084
TI  - Drugs used in child maltreatment.
AB  - Between 2000 and 2008, the American Association of Poison Control Centers
      recorded 1439 cases in which drugs or alcohol were used to mistreat children
      under 7 years of age, representing an average of 160 reports per year. Median age
      was 2 years, and 57% of victims were boys. The substances included psychotropic
      drugs, analgesics, cold remedies, alcohol, and illicit drugs. 18 children died,
      while 32 children experienced life-threatening effects or residual disability. It
      is not clear whether these results can be extrapolated to the French population.
      In France, a yearly survey of the Centres for Evaluation and Information on
      Pharmacodependence (CEIP) identified 162 cases of "chemical submission", 3 of
      which involved children. In practice, it is often difficult to recognise when a
      child is being maltreated, especially when medications, illicit drugs or alcohol
      are used. Taking into consideration the known adverse effect profile of a drug
      may provide a clue, help to limit harms to the child and allow appropriate
      management.

PMID- 21970085
TI  - Lopinavir + ritonavir oral solution: dangerous form for newborns.

PMID- 21970086
TI  - Methylphenidate: growth retardation.
AB  - Methylphenidate is an amphetamine psychostimulant used as a symptomatic treatment
      for attention-deficit hyperactivity disorder. A randomised trial examined changes
      in the height and weight of 521 hyperactive children. After 14 months, children
      treated with methylphenidate had gained less height and less weight (-1.23 cm per
      year and -2.48 kg per year) than untreated children. After 3 years, the
      differences were about 2 cm and 2.7 kg. Systematic reviews have provided similar
      results: methylphenidate slows growth by about 1 to 1.5 cm per year. Catch-up
      growth usually occurs during a 2-year period after methylphenidate withdrawal.
      Studies of final adult height have shown no statistically significant difference
      versus never-treated individuals. The effect of methylphenidate on growth is
      probably due to its impact in reducing appetite. Dexamfetamine is sometimes used
      as an alternative to methylphenidate and has similar effects on growth, as is the
      case with atomoxetine. In practice, prescription renewal provides a good
      opportunity to measure these children's growth. Marked growth retardation may
      warrant treatment interruption or a dose reduction.

PMID- 21970087
TI  - Syncope with cholinesterase inhibitors.
AB  - Adverse effects of cholinesterase inhibitors used in Alzheimer's disease include
      cardiac disorders (bradycardia, conduction disorders) that can cause malaise and
      syncope. A cohort study compared 20 000 patients who received a cholinesterase
      inhibitor for dementia with a control group of untreated dementia patients.
      Cholinesterase inhibitor therapy was associated with statistically significant
      increases in hospitalisations for syncope or bradycardia, pacemaker insertion,
      and hip fracture. In practice, cholinesterase inhibitors have little more than a
      placebo effect and do not justify exposing patients to these risks.

PMID- 21970088
TI  - Proton pump inhibitors: fractures (continued). Beware long-term use.

PMID- 21970089
TI  - Neuroleptics: intestinal occlusion. Antimuscarinic effects.

PMID- 21970090
TI  - Dronedarone: liver damage and cardiac disorders. Negative harm-benefit balance.

PMID- 21970091
TI  - Dasatinib: pulmonary arterial hypertension. French data.

PMID- 21970092
TI  - Treatment of Parkinson's disease. Psychological disorders: striking a balance in
      order to optimise antiparkinsonian treatment.
AB  - Parkinson's disease is frequently associated with psychological disorders,
      especially depression, psychotic disorders, and dementia. We examined the
      management of psychological disorders in Parkinson's disease, including the use
      of psychotropic drugs, by reviewing the literature using the standard Prescrire
      methodology. About one-third of patients with Parkinson's disease experience
      visual hallucinations. Other hallucinations and delusions can also occur. Dose
      reduction or withdrawal of certain antiparkinsonian drugs sometimes improves
      psychotic disorders, providing an acceptable level of symptom control. Clozapine
      is effective and does not worsen parkinsonian symptoms, but it carries a risk of
      severe adverse effects, including agranulocytosis. Other neuroleptics are
      ineffective or worsen motor status. Mood disorders and depression are frequent
      during the course of Parkinson's disease. Pramipexole, an antiparkinsonian
      dopamine agonist, improved depressive symptoms in patients with Parkinson's
      disease in one trial. Its main adverse effects are ocular disorders. Several
      trials have shown that some tricyclic antidepressants improve depression in
      Parkinson's patients, but these drugs can worsen cognitive status and cause
      postural hypotension. Data on selective serotonin reuptake inhibitor
      antidepressants (SSRIs) are unconvincing. A meta-analysis of three trials showed
      that treatment withdrawals due to adverse events were similarly frequent with
      tricyclics and SSRIs. Dementia is frequent in end-stage Parkinson's disease. When
      severe cognitive disorders occur, it is advisable to withdraw any drugs capable
      of worsening the situation, especially drugs with antimuscarinic effects and
      benzodiazepines. Cholinesterase inhibitors have a negative harm-benefit balance
      in this setting. When a Parkinson's patient presents with a psychological
      disorder, the first step is to optimise antiparkinsonian treatment by striking a
      balance between motor control and psychological adverse effects. In the few
      situations in which drug treatment is likely to be beneficial, it should be
      remembered that psychotropic drugs are at best only moderately effective and
      should be used with care, monitoring patients for adverse effects.

PMID- 21970093
TI  - Severe malaria: artesunate is now the standard treatment.

PMID- 21970094
TI  - Antiepileptic drug withdrawal in children.

PMID- 21970095
TI  - Atrial fibrillation: strict heart rate control provides no advantage.

PMID- 21970096
TI  - Prevention of recurrent gastrointestinal bleeding from peptic ulcers.

PMID- 21970097
TI  - Drug packaging. A key factor to be taken into account when choosing a treatment.
AB  - A drug's packaging contributes to its harm-benefit balance. Highlighting the key
      practical information and identifying potential sources of error or mix-ups is
      part and parcel of the correct use of medicines. Select labelling that clearly
      and prominently displays the important information, including the international
      nonproprietary name (INN).

PMID- 21970098
TI  - France's AME: medical apartheid.

PMID- 21970099
TI  - Trabectedin and ovarian cancer (continued).

PMID- 21970100
TI  - [One imported case of falciparum malaria in Harbin].

PMID- 21970101
TI  - [Cloning, expression and stage-specific analysis of Schistosoma japonicum P7
      antigen and evaluation of its value in early diagnosis].
AB  - OBJECTIVE: To clone and express Schistosoma japonicum P7 antigen (GenBank
      accession No. EU121231), analyze stage-specific transcription and expression of
      the antigen, and evaluate its value in early diagnosis. METHODS: The positive
      clone (P7) screened from schistosomula cDNA library was amplified by PCR. The PCR
      product was subcloned into prokaryotic expression vector pET28a. The recombinant
      plasmids were identified by restrictive enzymes digestion. The positive
      recombinant plasmids were transformed into E. coli BL21 (DE3), induced by IPG for
      expression and purified. The diagnostic value of P7 recombinant protein was
      evaluated by Western blotting analysis. RT-PCR and Western blotting were used to
      investigate the differential transcription and expression of P7 during the
      developmental stages. The specific antibodies against P7 recombinant protein in
      the sera of S. japonicum-infected rabbits at 14 d postinfection, sera of
      schistosomiasis (28 cases), clonorchiasis (30 cases) and paragonimiasis (20
      cases) patients, and sera of healthy people (30 cases) were detected by ELISA,
      respectively. RESULTS: The expression vector of p7/pET28a was established and the
      P7 recombinant protein (about Mr 20 100) was expressed in E. coli. Western
      blotting analysis showed that the recombinant protein was specifically recognized
      by immunized rabbit sera, and sera from mice on the 14th day post infection, but
      was not recognized by the sera of mice at 42 d post-infection. P7 mRNA was
      detected in cercariae, schistosomula and adult worms, while the protein was only
      found in schistosomula. The positive rate of rabbit sera collected at 14 d post
      infection was 83.3% (15/18). The sensitivity and specificity of ELISA for
      diagnosis of schistosomiasis japonica were 75.0% (21/28) and 93.8% (75/80),
      respectively. And the P7 protein showed cross reaction with sera of clonorchiasis
      and paragonimiasis patients with positive rates of 6.7% (2/30) and 5.0% (1/20),
      respectively. CONCLUSION: P7 antigen might be a potential candidate for early
      diagnosis of schistosomiasis.

PMID- 21970102
TI  - [Cloning, expression and immunodiagnostic evaluation of antigen EPC1 from
      Echinococcus granulosus].
AB  - OBJECTIVE: To clone and express EPCl gene of Echinococcus granulosus, and
      investigate its immunogenicity and diagnostic value. METHODS: Total RNA was
      extracted from hydatid cyst protoscoleces and EPC1 gene of Echinococcus
      granulosus was amplified by RT-PCR. The PCR product was cloned into pGEM-T
      vector, and then subcloned into the prokaryotic expression vector PET28a(+). The
      positive recombinants were transformed into Escherichia coli BL21 (DE3), and
      followed by expression of the protein induced by IPTG. The recombinant protein
      was identified by SDS-PAGE and Western blotting, and used to establish ELISA.
      Serum samples from patients with cystic echinococcosis (60 cases), alve-olar
      echinococcosis (37 cases), cysticercosis (16 cases), clonorchiasis sinensis (7
      cases), schistosomiasis japonica (4 cases) and healthy persons (33 cases) were
      examined. RESULTS: The recombinant plasmid PET28a-EgEPC1 was identified by
      restriction enzyme digestion and sequencing. SDS-PAGE result showed that the
      recombinant containing recombinant plasmid PET28a-EgEPC1 expressed a soluble
      fission protein of EgEPC1 (about M, 11 000). The protein was recognized by pool
      sera of cystic echinococcosis patients. The overall sensitivity and specificity
      of diagnosis by ELISA for cystic echinococcosis were 78.3% (47/60), and 98.3%
      (59/60), respectively. The cross reaction with sera of alveolar echinococcosis
      was 40.5% (15/37). CONCLUSION: The recombinant EgEPC1 antigen has diagnostic
      value in cystic echinococcosis.

PMID- 21970104
TI  - [Laboratory diagnosis of HIV/AIDS patients complicated with Pneumocystis
      jirovecii pneumonia].
AB  - Pneumocystis jirovecii was detected in sputum samples and bronchoalveolar lavage
      fluid (BALF) obtained from HIV/AIDS patients complicated with Pneumocystis
      jirovecii pneumonia by Giemsa staining. CD4+ T lymphocytes of 500 patients were
      counted by flow cytometer. P. jirovecii positive rate in sputum samples (46.8%,
      845/1 806) significantly lower than that of BALF (55.8%, 10(6)/190) (P < 0.05).
      The proportion of patients developing clinical symptoms in P. jirovecii positive
      cases (96.6%, 816/845) was higher than that of P. jirovecii negative cases
      (64.0%, 615/961) (P < 0.05). P. jirovecii positive rate increased with the
      decrease of CD4+ T lymphocyte number. P. jirovecii positive rates in cases with
      CD4+ > 200 x 10(6)/L, CDC 200 x 10(6)/L-100 x 10(6)n/L, and CD4+ <
      100x10(6)/12.0% (6/50), 39.0%( 39/100), 54.6% (191/350), respectively (P < 0.05).
      Giemsa staining is an efficient, simple and feasible method for P. jirovecii
      detection, relying on the experience and skill of the operator.

PMID- 21970103
TI  - [Evaluation of Clonorchis sinensis PPMP I antigen Cs2 recombinant protein for
      immunodiagnosis of clonorchiasis].
AB  - OBJECTIVE: To develop and preliminarily evaluate two immunodiagnostic methods for
      clonorchiasis using Clonorchis sinensis PPMP I antigen Cs2 recombinant protein
      (rCs2). METHODS: Using the soluble rCs2, an indirect ELISA and a colloidal-gold
      immuno-chromatography assay (GICA) dynamic flow strip was developed for detecting
      specific antibodies in serum. Serum samples from 35 egg-positive clonorchiasis
      patients, 33 healthy individuals, 15 schistosomiasis patients, 15 paragonimiasis
      westermani patients and 13 cysticercosis patients were examined by ELISA and GICA
      strip test. To further evaluate the diagnostic value of these two methods, eight
      New Zealand rabbits were randomly divided into infected group and treatment
      group. Each rabbit was infected with 600 C. sinensis metacercaria. Rabbits in
      treatment group were treated with praziquantel [150 mg/(kg x d) x 2d]
      individually at day 56 post-infection. ELISA and GICA strip test were used to
      observe the dynamic changes of specific antibodies against rCs2 in the two
      parallel groups during the period of 0-44 weeks. RESULTS: The sensitivity,
      specificity and total coincidence rate determined by the ELISA method were 71.4%
      (25/35), 93.4% (71/76), and 86.5% (96/111), respectively, and the cross reaction
      with schistosomiasis, paragonimiasis and cysticercosis patients were 1/15, 1/15,
      and 1/13, respectively. The sensitivity, specificity and coincidence rate in the
      GICA strip test were 85.7% (30/35), 92.1% (70/76), and 90.1%(100/111),
      respectively. In C sinensis infected rabbits, antibodies level began to increase
      at 4 weeks after infection, peaked at the 6th week, and declined rapidly to a
      lower level in the 20th week, while the changing pattern of antibodies level in
      the treatment group was similar with that of infected group (P > 0.05). In the
      GICA strip test, antibodies in two groups could be detected in 4-16 weeks.
      CONCLUSION: Indirect ELISA and the GICA dynamic flow strip developed in this
      study may be of value in the immunodiagnosis of clonorchiasis.

PMID- 21970105
TI  - [Cloning and expression of adenine phosphoribosyltransferase (APRT) and its
      differential expression analysis during the developmental stages of Schistosoma
      japonicum].
AB  - OBJECTIVE: To clone and express adenine phosphoribosyltransferase gene of
      Schistosoma japonicum, and analyze its stage-specific transcription and
      expression at different developmental stages of S. japonicum. METHODS: Specific
      primers were designed according to the reported EST sequence of SjAPRT1 gene
      (GenBank Accession No. AAW24796). RT-PCR was used to investigate the differential
      transcription of SjAPRT1 gene during the developmental stages. The gene was
      cloned into pET28a(+) plasmid. The recombinant plasmid rSjAPRT1/pET28a(+) was
      transformed into E. coli BL21(DE3) and induced with IPTG. The recombinant protein
      was purified with Ni-NTA resin and analyzed by SDS-PAGE. The purified protein was
      used to immune New Zealand white rabbits to obtain the antiserum. Western
      blotting was used to investigate the immunogenicity and the differential
      expression of rSjAPRT1 at different developmental stages. RESULTS: RT-PCR result
      showed that the specific bands were detected in eggs, cercariae, schistosomula,
      and adult worms (561 bp). Western blotting analysis showed that the recombinant
      protein (rSjAPRT1, about Mr 25 000) existed in eggs, schistosomula and adult
      worms. The recombinant protein was recognized by pooled sera of infected rabbits.
      CONCLUSION: The recombinant protein (rSjAPRT1) shows specific immunoreactivity,
      and is detected in the stage of eggs, schistosomula, and adult worms.

PMID- 21970106
TI  - [Anti-hepatofibrosis effect of fasudil hydrochloride on Schistosoma japonicum
      infected mice].
AB  - OBJECTIVE: To investigate the anti-fibrotic effect of fasudil hydrochloride on
      Schistosoma japonicum-infected mice, and the effect of fasudil hydrochloride on
      hepatic stellate cells (HSCs). METHODS: Thirty female BALB/c mice were randomly
      divided into 3 groups viz, normal control group (NC group), infection group, and
      experiment group. Mice in both infection group and experiment group were infected
      with (14:2) cercariae of S japonicum. At 6 weeks post infection, mice in
      experiment group were intraperitoneally injected with fasudil hydrochloride (10
      mg/kg) twice a day for 7 d, while mice in NC group and infection group received
      the same volume of physiological saline. All mice were sacrificed 12 h after the
      last injection. Livers from NC group and infection group were used to prepare
      tissue sections for hematoxylin and eosin (HE) staining, or sirius red staining,
      and observed under light microscope. Livers from all three groups were used to
      detect content of hydroxyproline (Hyp) and the mRNA expressions of alpha-smooth
      muscle actin (alpha-SMA), type I collagen alpha1 (Col1alpha1) and epithelial cell
      transforming sequence 2 (Ect2). HSCs from mice in all three groups were isolated
      to detect the mRNA levels of alpha-SMA, Col1alpha1, and Ect2, respectively.
      RESULTS: Pathological sections showed that in livers from mice in infection
      group, inflammatory cells infiltrated and collagenous fibre proliferated around
      portal areas and egg granulomas. The content of Hyp in liver from mice of NC
      group, infection group, and experiment group was (279.7 +/- 21.2) microg, (528.0
      +/- 15.0) microg, and (355.4 +/- 22.6) microg, respectively. The content of Hyp
      in livers from mice of experiment group was significantly reduced compared to
      infection group (P < 0.01). The mRNA expression of alpha-SMA, Col1alpha1 and Ect2
      in livers and HSCs from mice in experiment group were significantly down
      regulated compared to infection group (P < 0.05). CONCLUSION: Fasudil
      hydrochloride can depress hepatofibrosis in Schistosoma japonicum-infected mice.

PMID- 21970107
TI  - [Total protein analysis by two-dimensional electrophoresis in cysticerci of
      Taenia solium and Taenia asiatica].
AB  - Two 20-day-old three-way crossed hybrid pigs were infected with 80000 Taenia
      solium or T. asiatica eggs, respectively. Immature cysticerci of the two species
      in liver were collected at 40 days after infection. The total proteins were
      separated by two-dimensional electrophoresis, and differentially expressed
      proteins were analyzed by Image-Master 2D Platinum 6.0 software. The results
      showed that there were (236 +/- 12) and (231 +/- 14) protein spots in 2D
      electrophoresis gel images of T. solium and T. asiatica, respectively, with 3
      proteins up-regulated and 7 proteins down-regulated in T. solium cysticercus by 2
      fold or more compared with those in T. asiatica cysticercus.

PMID- 21970108
TI  - [Cloning, expression and purification of arginine kinase from Blattella germanica
      and its immune activity].
AB  - OBJECTIVE: To clone and express the arginine kinase (AK) gene of Blattella
      germanica and analyze its immune activity. METHODS: The cDNA of AK was cloned
      using specific primers from the total RNA of Blattella germanica The open reading
      frame (ORF) of AK was cloned into pET-28A vector, and expressed in Escherichia
      coli BL21(DE3) with IPTG induction. The recombinant protein was purified by Ni2+
      chelating affinity chromatography. The recombinant protein was detected by SDS
      PAGE, and its immune activity was analyzed by Western blotting. RESULTS: The
      cloned cDNA ORF sequence (GenBank accession No. FJ514482) contained 1071bp and
      encoded 356 amino acids. Its sequence homology with the published one (GenBank
      accession No. EU429466) was 97.2% at nucleotide level. The recombinant containing
      recombinant plasmid pET-28a-AK expressed a soluble protein of AK (Mr 45 000)
      after being induced with IPTG. The recombinant AK protein was recognized by sera
      of allergic patients, indicating that the recombinant AK protein has an adequate
      response activity. CONCLUSION: The AK gene of Blattella germanica has been cloned
      and the recombinant AK protein has been confirmed with immune activity.

PMID- 21970109
TI  - [Preliminary study on the comprehensive evaluation method of schistosomiasis
      health education--a field study in a heavy endemic area in lake region].
AB  - OBJECTIVE: To explore a comprehensive evaluation method of knowledge, attitude
      and behavior (KAP) about schistosomiasis control among students of susceptibility
      zone in lake region. METHODS: A comprehensive KAP evaluation indicator system was
      developed by using analytic hierarchy process (AHP). The system consists of three
      layers. First-layer indices include knowledge, altitude and behavior of
      schistosomiasis control. 17 specific parts compose second-layer indices. Third
      layer indices have 30 specific aspects. The experts were invited to provide
      comments for these indicators, and indicator weights were formulated by using
      AHP. A questionnaire survey was conducted among students of grade 3 and 4 from
      Central Primary School, Liyuzhou Primary School and Meichi Primary School in
      Wuxing Farm. Status of health education for schistosomiasis was evaluated by this
      method. RESULTS: n the indicator system, the weights of behavior, altitude and
      knowledge were 0.54, 0.30, and 0.16, respectively. The average score of KAP
      indicator was 8.45. The score for behavior, altitude and knowledge indicators was
      8.86, 8.90, and 6.25, respectively. The scores of some indicators such as fishing
      outside and inside level, washing outside level and grazing in marshland were
      8.17-9.29. CONCLUSION: This comprehensive evaluation method can be used to
      evaluate basic situation and effect of health education in schistosomiasis
      intervention. The health education should be strengthened in the survey site.

PMID- 21970110
TI  - [Resistance assay of malaria vectors to four kinds of common insecticides in some
      endemic areas of Hainan Province].
AB  - OBJECTIVE: To determine the resistance of malaria vectors to four kinds of common
      insecticides in some endemic areas of Hainan Province. METHODS: Anopheline
      mosquitoes were collected between 2008 and 2010 from malaria endemic areas where
      insecticides were used for years. Anopheles dirus were collected from human
      baited trap in Wangxia Town of Changjiang County. An. minimus and An. sinensis
      were collected by cow-baited trap in Jiangbian Town of Dongfang City. F0
      generation female An. sinensis, F1 generation of female An. dirus and An. minimus
      were selected and exposed to insecticide impregnated papers with discriminating
      concentrations of DDT (4%), deltamethrin (0.05%), cyfluthrin (0.15%), and
      malathion (5%) using WHO standard assays. Knockdown rate was recorded at 10, 15,
      20, 30, 40, 50, and 60 min, and KTm values were calculated. Mortality was
      recorded after 24 hours of exposure. RESULTS: Mortality in An. dirus was 100% to
      DDT, deltamethrin and malathion. Knockdown rate of An. dirus exposed to DDT and
      deltamethrin was 82.0% and 100%, with a KT50 value of 46.9 and 18.4 min,
      respectively. Mortality of An. minimus to DDT, deltamethrin, cyfluthrin and
      malathion was 98.1%, 99.0%, 100%, and 100%, respectively. The knockdown rate of
      An. minimus to DDT, deltamethrin, and cyfluthrin was 96.3%, 99.0%, and 100%,
      respectively, and the KTs value was 31.3, 16.8, and 7.4 min, respectively.
      Mortality of An. sinensis to DDT, deltamethrin, and malathion was 19.8%, 22.9%,
      and 43.8%, respectively. Knockdown rate of An. sinensis to DDT and deltamethrin
      was 2.0%, the KT50 can not be calculated. CONCLUSION: An. dirus and An. minimus,
      the main malaria vectors in the survey sites of Hainan Province, are susceptible
      to the four insecticides, while secondary malaria vector An. sinensis showed
      resistance to DDT, deltamethrin, and malathion.

PMID- 21970111
TI  - [Cloning, expression and purification of silent information regulator 2 from
      Giardia lamblia].
AB  - OBJECTIVE: To clone and express silent information regulator 2 (Sir2) gene from
      Giardia lamblia. METHODS: The GlSir2 gene was amplified by PCR from genomic DNA
      of Giardia lamblia (Chinese strain C2 clone). PCR product was cloned into pMD-19T
      vector and transformed into E coli JM109. The recombinant plasmid was sequenced
      and then cloned into the pET28b vector. The pET28b-Gl1Sir2 recombinant plasmid
      was transformed into E. coli BL21(DE3), followed by expression of the protein
      induced by IPTG. The recombinant protein was analyzed by SDS-PAGE. Inclusion
      bodies were dissolved with 8 mol/L urea, and the supernatant was collected and
      applied to Ni2+ affinity chromatography. The purified recombinant protein was
      renatured by dialysis and verified by Western blotting using anti-His tag
      antibody. RESULTS: GlSir2 gene sequence was cloned. The GISir2 open reading frame
      (1 680 bp) encoded a 559-amino acid protein with Mr 62 800. The recombinant
      plasmid pET28b-GlSir2 expressed an inclusion body protein of GISir2 after being
      induced with IPTG. The protein purity reached above 80% after purification. The
      purified protein was renatured by dialysis. The recombinant GISir2 was recognized
      by anti-His tag antibody. CONCLUSION: The coding sequence of GLSir2 gene was
      cloned and expressed in vitro. The recombinant protein was identified by anti-His
      tag antibody.

PMID- 21970112
TI  - [X-ray irradiation against Echinococcus multilocularis protoscoleces in vitro].
AB  - OBJECTIVE: To explore the effect of X-ray irradiation on Echinococcus
      multilocularis protoscoleces in vitro. METHODS: Echinococcus multilocularis
      protoscoleces were collected from cysts of infected Meriones meridianus and then
      cultured in RPMI 1640 medium. Protoscoleces were subpackaged into culture flasks
      at a density of about 10(4) per flask after culture for 3 days. Each group has 10
      culture flasks. There were seven groups named as blank control group, low dose
      group (15 Gy and 30 Gy), medium dose group (45 Gy and 60 Gy), high dose group (75
      Gy and 90 Gy), albendazole group (2 500 ng/ml), 45 Gy X-ray + 2 500 ng/ml
      albendazole group, and 75 Gy X-ray + 2 500 ng/ml albendazole group. Protoscoleces
      received three radiations on every other day with a source-skin distance of 100
      cm and at a dose rate of 200 cGy/min after 3 days in culture. At each day after
      irradiation, protoscoleces were counted by light microscope with 0.1% eosin
      staining, and calculated mortality rate (per 100 protoscoleces) until all the
      parasites in experimental groups died. At the same time, the morphological
      changes of protoscoleces were observed. RESULTS: There were significant
      differences in protoscolex mortality between X-ray groups and blank control group
      (P < 0.05), between X-ray + albendazole groups and albendazole group (P < 0.05).
      Protoscolex mortality in albendazole group were higher than that of blank control
      group (P < 0.05). Significant difference were also found in protoscolex mortality
      between albendazole combined with radiation and radiation only (P < 0.05). Before
      radiation, protoscoleces was normal with complete structure. After radiation, the
      parasites were mostly valgus type protoscoleces with disordered rostellar hooks
      and deformed acetabulum, and finally died. CONCLUSION: X-ray can kill
      Echinococcus multilocularis protoscoleces in vitro.

PMID- 21970113
TI  - [Strengthening the research on clonorchiasis in China].
AB  - Liver flukes mainly include Clonorchis sinensis, Opisthorchis viverrini, and
      Opisthorchis felineus. The international congress of liver flukes was held in
      Khon Kaen, Thailand, during 7-8th March, 2011. The congress assembled a wide
      array of studies and reflected the current status of research, control and
      prevention of liver flukes in the world. This paper summarizes basic information
      from the meeting. Meanwhile, based on the research status and needs for control
      and prevention, priorities of research on clonorchiasis in China are discussed.

PMID- 21970114
TI  - [Research progress on the molecular pathogenesis of Trichomonas vaginalis].
AB  - Trichomonas vaginalis is one of the most common human sexually transmitted
      pathogens that colonize the urogenital mucosa. This paper reviews those factors
      in the molecular pathogenesis of the parasite, including cell adhesin,
      interaction with fibronectin and laminin, G-proteins, pore-forming protein and
      proteinases.

PMID- 21970115
TI  - [Alternatively activated macrophages in helminth infections].
AB  - Macrophages not only initiate and modulate immune responses, but also are the
      final effector cells. Recent studies suggested that macrophages conventionally
      associated with IFN-gamma dominant Th1-type responses and also playing an
      essential role in the Th2-type inflammatory response, exhibit a quite different
      activation from the classically activated macrophages (CAM Phi) stimulated during
      Th1-type responses, therefore named as alternatively activated macrophages (AAM
      Phi). AAM Phi have multiple effects during helminth infection, including control
      of inflammatory reaction, contribution to fibrosis and repair at the site of
      injury, and anti-helminth effect. This article reviews recent findings regarding
      the role of AAM Phi in the development of disease and host protection following
      helminth infection.

PMID- 21970116
TI  - [Application and progress of fluorescence in situ hybridization in schistosome
      biology].
AB  - Schistosomiasis is one of the most serious parasitic diseases. Schistosome genes
      research provides the basis for study of schistosomiasis diagnosis, vaccine and
      drug targets. Fluorescence in situ hybridization (FISH) in schistosome focuses on
      researches of location of functional genes on chromosomes, genome physical
      mapping and chromosome identification. This article reviews the application of
      FISH in schistosome biology and its potential development.

PMID- 21970117
TI  - [Progress on classification and identification of Acanthamoeba].
AB  - As a pathogenic free-living amoeba, Acanthamoeba is easy to be recognized at the
      genus level, but difficult to identify at species level on the morphological
      basis. This review summarizes the methods for Acanthamoeba species classification
      and identification.

PMID- 21970118
TI  - [Design and trial of computer test system for experiment courses of human
      parasitology].
AB  - Based on the traditional experimental test of human parasitology, a reform was
      conducted to avoid the shortage of specimens and a disclosure of test questions.
      An experimental test system of human parasitology based on client/server (C/S)
      structure was therefore developed. This practicable system can increase the
      efficiency and fairness of examination and reduce cost.

PMID- 21970119
TI  - [An efficient and accurate method for counting target molecules in phage-display
      peptide library].
AB  - The phage titer of samples representing the low, intermediate and high phage
      number was respectively determined by the double-layer agar plate (DLAP) method
      and real-time PCR assay. The two methods accurately measured the titer of
      samples. The plaques from about 1/3 double-agar layer plates could be used to
      determine the phage titer. The DLAP experiment should repeat 10 times with 10
      microl sample each time, while the within-assay coefficient variation (CV) was
      4.93%-30.38%. At the same time, the real-time PCR assay only repeated 3 times
      with 1 microl phage each time, while CV for within-assay ranged from 0.02% to
      0.25%. Results indicated that real-time PCR is a simple and quick method for
      determining bacteriophage titer.

PMID- 21970120
TI  - [Serological detection of Cryptosporidium spp. infection in outpatients in
      Changchun].
AB  - CP23 gene of Cryptosporidium parvum was expressed in Escherichia coli, and the
      recombinant protein was purified. Its immunoreactivity was analyzed by Western
      blotting. Serum samples were collected from outpatients of different ages from
      August to November, 2010 in Changchun. Indirect ELISA was established to detect
      the anti-CP23 IgG in sera. Western blotting analysis indicated that the
      recombinant CP23 protein was recognized by sera from Cryptosporidium panum
      infected calves and positive human sera, but not recognized by sera of mice
      infected with Schistosoma japonicum, sera from falciparum malaria patients and
      negative human sera. The overall anti-CP23 IgG positive rate was 3.2% (65/2 046).
      The seropositive rate was 2.7% (28/1 036) in men and 3.7% (37/1 010) in women (P
      > 0.05). The seropositive rates were significantly different among age groups (P
      < 0.05), and the age group of 71-80 had the highest positive rate (8.6%, 13/152).

PMID- 21970121
TI  - Patient-controlled analgesia syringe pumps.

PMID- 21970122
TI  - High frequency oscillation in the adult intensive care unit. Nearly mainstream?

PMID- 21970123
TI  - Ten commandments of interpreting and applying results of biomarker research.

PMID- 21970124
TI  - Hypocoagulability, hypercoagulability and the interpretation of 'normal' kaolin
      activated thrombelastographs in the perioperative period.

PMID- 21970125
TI  - Acute pain management in opioid-tolerant patients: a growing challenge.
AB  - In Australia and New Zealand, in parallel with other developed countries, the
      number of patients prescribed opioids on a long-term basis has grown rapidly over
      the last decade. The burden of chronic pain is more widely recognised and there
      has been an increase in the use of opioids for both cancer and non-cancer
      indications. While the prevalence of illicit opioid use has remained relatively
      stable, the diversion and abuse of prescription opioids has escalated, as has the
      number of individuals receiving methadone or buprenorphine pharmacotherapy for
      opioid addiction. As a result, the proportion of opioid-tolerant patients
      requiring acute pain management has increased, often presenting clinicians with
      greater challenges than those faced when treating the opioid-naive. Treatment
      aims include effective relief of acute pain, prevention of drug withdrawal,
      assistance with any related social, psychiatric and behavioural issues, and
      ensuring continuity of long-term care. Pharmacological approaches incorporate the
      continuation of usual medications (or equivalent), short-term use of sometimes
      much higher than average doses of additional opioid, and prescription of non
      opioid and adjuvant drugs, aiming to improve pain relief and attenuate opioid
      tolerance and/or opioid-induced hyperalgesia. Discharge planning should commence
      at an early stage and may involve the use of a 'Reverse Pain Ladder' aiming to
      limit duration of additional opioid use. Legislative requirements may restrict
      which drugs can be prescribed at the time of hospital discharge. At all stages,
      there should be appropriate and regular consultation and liaison with the
      patient, other treating teams and specialist services.

PMID- 21970126
TI  - The transition from acute to chronic post surgical pain.
AB  - All chronic pain was once acute, but not all acute pain becomes chronic. The
      transition of acute postoperative pain to chronic post surgical pain is a complex
      and poorly understood developmental process. The manuscript describes the various
      factors associated with the transition from acute to chronic pain. The
      preoperative, intraoperative and postoperative surgical, psychosocial, socio
      environmental and patient-related factors and the mechanisms involved are
      discussed and preventive (or limitation) strategies are suggested. In future, the
      increasing understanding of genetic factors and the transitional mechanisms
      involved may reveal important clues to predict which patients will go on to
      develop chronic pain. This may assist the development of appropriate
      interventions affecting not only the individual concerned, but also ultimately
      the community at large.

PMID- 21970127
TI  - Experience with high frequency oscillation ventilation during the 2009 H1N1
      influenza pandemic in Australia and New Zealand.
AB  - During the 2009 H1N1 pandemic, large numbers of patients had severe respiratory
      failure. High frequency oscillation ventilation was used as a salvage technique
      for profound hypoxaemia. Our aim was to compare this experience with high
      frequency oscillation ventilation during the 2009 H1N1 pandemic with the same
      period in 2008 by performing a three-month period prevalence study in Australian
      and New Zealand intensive care units. The main study end-points were clinical
      demographics, care delivery and survival. Nine intensive care units contributed
      data. During 2009 there were 22 H1N1 patients (17 adults, five children) and 10
      non-H1N1 patients (five adults, five children), while in 2008, 18 patients (two
      adults, 16 children) received high frequency oscillation ventilation. The
      principal non-H1N1 high frequency oscillation ventilation indication was
      bacterial or viral pneumonia (56%). For H1N1 patients, the median duration of
      high frequency oscillation ventilation was 3.7 days (interquartile range 1.8 to
      5) with concomitant therapies including recruitment manoeuvres (22%), prone
      ventilation (41%), inhaled prostacyclins (18%) and inhaled nitric oxide (36%).
      Seven patients received extracorporeal membrane oxygenation, six having H1N1.
      Three patients had extracorporeal membrane oxygenation concurrently, two as
      salvage therapy following the commencement of high frequency oscillation
      ventilation. In 2008, no high frequency oscillation ventilation patient received
      extracorporeal membrane oxygenation. Overall hospital survival was 77% in H1N1
      patients, while survival in patients having adjunctive extracorporeal membrane
      oxygenation was similar to those receiving high frequency oscillation ventilation
      alone (65% compared to 71%, P = 1.00). Survival rates were comparable to
      published extracorporeal membrane oxygenation outcomes. High frequency
      oscillation ventilation was used successfully as a rescue therapy for severe
      respiratory failure. High frequency oscillation ventilation was only available in
      a limited number of intensive care units during the H1N1 pandemic.

PMID- 21970128
TI  - Markers of coagulation activation after hepatic resection for cancer: evidence of
      sustained upregulation of coagulation.
AB  - We investigated the possibility that despite postoperative derangements of
      routine laboratory coagulation tests, markers of coagulation activation and
      thrombin generation would be normal or increased in patients undergoing hepatic
      resection for cancer In addition to the conventional coagulation tests
      prothrombin time and activated partial thromboplastin time, we measured select
      markers of coagulation activation prothrombin fragments 1 and 2 (PF1 + 2),
      thrombin-antithrombin complexes and plasma von Willebrand Factor antigen in 21
      patients undergoing hepatic resection. The impact of hepatic resection on
      coagulation and fibrinolysis was studied with thromboelastography.
      Preoperatively, routine laboratory coagulation and liver function tests were
      normal in all patients. On the first postoperative day, prothrombin time was
      prolonged (range 16 to 22 seconds) in eight patients (38%). For these patients,
      thromboelastography was normal in six (75%), PF1 + 2 was elevated in four (50%),
      and thrombin-antithrombin complexes and von Willebrand Factor antigen were
      elevated in all, which was evidence of acute phase reaction, sustained
      coagulation factor turnover and activation. By the fifth postoperative day,
      despite normalisation of prothrombin time, markers of increased coagulation
      activity remained greater than 85% of baseline values. The findings indicate that
      in patients undergoing liver resection for cancer, there is significant and
      prolonged postoperative activation of the haemostatic system despite routine
      coagulation tests being normal or even prolonged. Before considering therapeutic
      interventions an integrated approach to interpreting haematological data with
      clinical correlation is essential.

PMID- 21970129
TI  - C-reactive protein as a predictor of mortality in critically ill patients: a meta
      analysis and systematic review.
AB  - C-reactive protein is a marker of inflammatory response and has been widely
      investigated in cardiovascular and infectious diseases, especially to monitor
      therapeutic success. However, its role as a predictor of clinical outcome in
      critically ill patients remains uncertain and controversial. The objective of
      this study was to investigate the predictive value of C-reactive protein in
      critically ill patients. The databases of PubMed, the Cochrane clinical trial
      database and EMBASE (from inception to August 2010) were searched. Prospective
      non-randomised clinical studies comparing C-reactive protein concentrations
      between survivors and non-survivors were included. Pooled mean difference in C
      reactive protein concentrations between survivors and non-survivors was
      calculated. Heterogeneity was analysed by I2. Sensitivity and subgroup analyses
      were conducted to explore the heterogeneity. Fourteen studies containing a total
      of 1969 patients were finally included in our analysis. The weighted mean
      difference in the C-reactive protein levels between survivors and non-survivors
      was 9.15 mg/l (95% confidence interval -6.50 to 24.81). The heterogeneity was
      large with I2 = 92%. Subsequent investigation of the heterogeneity with
      sensitivity analyses yielded no significant differences. The subgroup analysis
      showed that the weighted mean difference in early (within 48 hours) C-reactive
      protein levels between survivors and non-survivors was not significantly
      different, in contrast to the late (beyond 48 hours) C-reactive protein level.
      This was significantly greater in non-survivors with a weighted mean difference
      of 63.80 mg/l (95% confidence interval 35.67 to 91.93). Our systematic review
      shows that while the early C-reactive protein concentration is not a good
      predictor of survival in critically ill patients, the late C-reactive protein
      concentration may help to identify patients who are at risk of death.

PMID- 21970130
TI  - Initial lactate level and mortality in septic shock patients with hepatic
      dysfunction.
AB  - An elevated serum lactate level is associated with morbidity and mortality in
      patients with severe sepsis and septic shock. In patients with hepatic
      dysfunction, however an elevated serum lactate level may be due to either
      impaired lactate clearance or excessive production. Thus, we evaluated whether
      the initial serum lactate level was also associated with mortality in septic
      shock patients with hepatic dysfunction. A retrospective observational study
      enrolled 307 patients with septic shock admitted to the intensive care unit (ICU)
      between May 2007 and July 2009. Hepatic dysfunction was defined as a serum total
      bilirubin > 34.2 micromol/l (2 mg/dl). Selected patients were divided into high
      (> or = 4 mmol/l) and low (< 4 mmol/l) lactate groups, according to the initial
      serum lactate level. Of 307 patients with septic shock, 118 (38%) patients with
      hepatic dysfunction were eligible for this study. The median lactate levels were
      5.9 (interquartile range 4.7 to 9.0) and 2.6 (interquartile range 1.7 to 3.2)
      mmol/l for the high and low lactate groups respectively (P < 0.001). The initial
      serum lactate level was strongly associated with in hospital mortality in a
      univariate analysis (P < 0.001). After adjusting for potential confounding
      factors, the initial serum lactate level remained significantly associated with
      in-hospital mortality (odds ratio 1.281, 95% confidence interval 1.097 to 1.496,
      P = 0.002). In conclusion, the serum lactate level could be useful in predicting
      the outcome of patients with septic shock regardless of hepatic dysfunction.

PMID- 21970131
TI  - Cardiac output and propofol concentrations in prone surgical patients.
AB  - The aim of this study was to compare cardiac output and plasma propofol
      concentrations in the supine and prone positions in healthy adult patients
      presenting for lumbar spine surgery. Patients received propofol and remifentanil
      via effect-site steered target-controlled infusions. Cardiac output and plasma
      propofol concentration were compared during 20 minutes in the supine position and
      20 minutes after positioning on a Wilson frame. Cardiac output did not change
      significantly over 20 minutes in either position (P = 0.37) and was similar at 20
      minutes in the supine (6.1 [1.6] l/minute) and prone positions (6.1 [1.9]
      l/minute) (P = 0.87). Propofol concentrations were similar in the supine and
      prone positions at 20 minutes (2.55 [0.89] and 2.53 [0.90] microg/ml; P = 0.93).
      We conclude that prone positioning on the Wilson frame does not affect cardiac
      output or plasma propofol concentration.

PMID- 21970132
TI  - The association between intraoperative electroencephalogram-based measures and
      pain severity in the post-anaesthesia care unit.
AB  - This observational study aimed to identify simple electroencephalogram indices of
      inadequate intraoperative opioid-mediated nociceptive blockade and to compare
      these indices with routinely used clinical predictors of severe postoperative
      pain in adults. Intraoperative trend and waveform data (electrocardiogram, pulse
      oximetry and electroencephalogram) were collected, pain intensity in the post
      anaesthesia care unit was quantified using an 11-point Verbal Rating Score, and
      opioid administration was recorded. Using the initial post-anaesthesia care unit
      Verbal Rating Score as the primary endpoint, the relationship between five
      possible explanatory variables--surgery type, depth of volatile anaesthesia
      (minimum alveolar concentration), electroencephalogram signs (state entropy,
      spindle-like activity and delta-band power) and estimated end-of-operation effect
      site morphine concentrations--was examined. One hundred and thirteen patients
      were recruited, with 94 included in the final clinical and electroencephalogram
      data analysis. Fifty-two patients had moderate or severe pain (Verbal Rating
      Score > or = 5). State entropy was lower (46.5 +/- 2.9 vs 43.1 +/- 1.9, P = 0.04)
      and spindle-like activity higher (0.42 +/- 0.03 vs 0.50 +/- 0.02, P = 0.03) in
      the moderate/severe pain group. [corrected] These findings suggest that there is
      a modest association between electroencephalogram measures near the end of
      surgery and the severity of postoperative pain.

PMID- 21970133
TI  - The effect of a graphical interpretation of a statistic trend indicator (Trigg's
      Tracking Variable) on the detection of simulated changes.
AB  - Anaesthesia involves processing large amounts of information over time. One task
      of the anaesthetist is to detect substantive changes in physiological variables
      promptly and reliably. It has been previously demonstrated that a graphical trend
      display of historical data leads to more rapid detection of such changes. We
      examined the effect of a graphical indication of the magnitude of Trigg's
      Tracking Variable, a simple statistically based trend detection algorithm, on the
      accuracy and latency of the detection of changes in a micro-simulation. Ten
      anaesthetists each viewed 20 simulations with four variables displayed as the
      current value with a simple graphical trend display. Values for these variables
      were generated by a computer model, and updated every second; after a period of
      stability a change occurred to a new random value at least 10 units from
      baseline. In 50% of the simulations an indication of the rate of change was given
      by a five level graphical representation of the value of Trigg's Tracking
      Variable. Participants were asked to indicate when they thought a change was
      occurring. Changes were detected 10.9% faster with the trend indicator present
      (mean 13.1 [SD 3.1] cycles vs 14.6 [SD 3.4] cycles, 95% confidence interval 0.4
      to 2.5 cycles, P = 0.013. There was no difference in accuracy of detection
      (median with trend detection 97% [interquartile range 95 to 100%], without trend
      detection 100% [98 to 100%]), P = 0.8. We conclude that simple statistical trend
      detection may speed detection of changes during routine anaesthesia, even when a
      graphical trend display is present.

PMID- 21970134
TI  - Safety of exposure of malignant hyperthermia non-susceptible patients and their
      relatives to anaesthetic triggering agents.
AB  - As the reliability of malignant hyperthermia normal in vitro contracture test
      results has been questioned, this study set out to determine the reliability of
      malignant hyperthermia normal results in New Zealand. Three hundred and twenty
      nine anaesthetics were administered to malignant hyperthermia normal patients,
      identified through the Palmerston North Hospital malignant hyperthermia database.
      Anaesthetic records were retrieved and scrutinised for a malignant hyperthermia
      reaction using the Malignant Hyperthermia Clinical Grading Scale. Patients were
      exposed to one or more of eight triggering agents and multiple anaesthetic agents
      were administered in 41% of cases. Six variables were analysed, and although a
      minority of variables were abnormal in a small number of patients, none of the
      findings supported a malignant hyperthermia reaction. While the analysis was
      limited by the adequacy of the anaesthesia records, it was supported by negative
      DNA analysis in 55% of patients. This study supports several previous studies in
      demonstrating that patients in New Zealand tested non-susceptible to malignant
      hyperthermia can safely be given triggering agents.

PMID- 21970135
TI  - Adverse events in the removal of naltrexone implants.
AB  - Naltrexone implants are used as an abstinence therapy for patients with opioid,
      amphetamine and alcohol abuse. This study was designed to assess the implications
      of this therapy in patients presenting for anaesthesia for removal of these
      implants. We conducted a retrospective case-note review of 37 patients undergoing
      removal of naltrexone implants in the period 2001 to 2008 at Sir Charles Gairdner
      Hospital. Indications for removal included infection at the insertion site,
      naltrexone intolerance or the requirement for effective opioid analgesia. Thirty
      two patients had surgery under general anaesthesia, four under local anaesthesia
      and one under spinal anaesthesia. The perioperative opioid requirement varied
      from 0 to 100 mg of intravenous morphine equivalents (median 11.7 mg, mean 20.7
      mg). The only factor that was associated with a higher perioperative opioid
      requirement was whether the implant was infected or not. Forty-four percent of
      patients having a general anaesthetic complained of moderate to severe pain
      postoperatively, and 64% of these patients had a prolonged stay in the post
      anaesthesia care unit. We did not observe any instances of postoperative
      complications due to increased opioid sensitivity after removal of naltrexone
      implants. The majority of patients were discharged home by the first
      postoperative day. Anaesthesia for the removal of naltrexone implants was
      associated with a wide range of opioid analgesia requirements and a high
      incidence of pain postoperatively. Concern regarding increasing opioid
      sensitivity after removal of implants does not seem to preclude use of generous
      opioid analgesia in this group of patients.

PMID- 21970136
TI  - Optimum bolus dose of propofol for tracheal intubation during sevoflurane
      induction without neuromuscular blockade in children.
AB  - The purpose of this study was to determine the optimum bolus dose of propofol
      required to provide excellent conditions for tracheal intubation following
      inhalational induction of anaesthesia using 5% sevoflurane without neuromuscular
      blockade. Twenty-eight children, aged three to seven years, requiring anaesthesia
      for short duration surgery were recruited. Two minutes after beginning the
      inhalational induction with 5% sevoflurane and 60% nitrous oxide, a predetermined
      dose of propofol was injected over 10 seconds. Propofol dose was determined using
      the Dixon's up-and-down method, starting from 3 mg/kg (0.5 mg/kg as a step size).
      Laryngoscopy was performed 50 seconds after propofol injection. The optimum dose
      of propofol required for excellent intubating conditions was 1.39 +/- 0.37 mg/kg
      in 50% of children during inhalation induction using 5% sevoflurane and 60%
      nitrous oxide in the absence of neuromuscular blocking agents. From probit
      analysis, the 95% effective dose of propofol was 2.33 mg/kg (95% confidence
      interval 1.78 to 6.21 mg/kg).

PMID- 21970137
TI  - Prophylactic use of midazolam or propofol at the end of surgery may reduce the
      incidence of emergence agitation after sevoflurane anaesthesia.
AB  - Sevoflurane is associated with a high incidence of emergence agitation in
      children. Midazolam and propofol have been examined with the aim of reducing
      emergence agitation after sevoflurane anaesthesia. However the effect of both
      drugs on emergence agitation is still controversial. Therefore we designed this
      study to measure the effect of midazolam or propofol at the end of surgery on
      emergence agitation during the recovery period. One hundred and one children,
      aged one to 13 years, undergoing strabismus surgery were enrolled in this
      randomised double-blind study. Anaesthesia was induced and maintained with
      sevoflurane in N2O/O2. Children were randomly assigned to receive midazolam 0.05
      mg/kg (group M, n = 35), propofol 1 mg/kg (group P, n = 31) or saline (group S, n
      = 35). A four-point scale was used to evaluate recovery characteristics upon
      awakening and during the first hour after emergence from anaesthesia. The
      incidence of emergence agitation in group M was 42.9% (15/35), in group P 48.4%
      (15/31) and in group S 74.3% (26/35). The incidence of emergence agitation in
      groups M and P was significantly less than in group S. The emergence time was
      prolonged for patients in groups M and P compared to group S. There was no
      significant difference in the incidence of emergence agitation or in emergence
      times between the groups P and M. We conclude that propofol or midazolam
      administration before the end of surgery may be effective in reducing the
      incidence of emergence agitation in children undergoing strabismus surgery under
      sevoflurane anaesthesia.

PMID- 21970138
TI  - Single level paravertebral versus caudal block in paediatric inguinal surgery.
AB  - Paravertebral block (PVB) has been used for postoperative analgesia in children
      since 1992. There are no prospective randomised studies comparing the use of PVB
      versus caudal block (CB) for outpatient inguinal hernia repair surgery. The
      hypothesis of this study is that a single level, single injection PVB can provide
      a longer duration of analgesia and less requirement for supplemental analgesia
      than single shot CB for children undergoing inguinal surgery. Seventy children,
      aged three to seven, American Society of Anesthesiologists score I to II, having
      unilateral inguinal surgery were enrolled in the study. The patients were divided
      into two randomised groups. In group PVB, a single shot of 0.2 ml/kg
      levobupivacaine was administered via the lumbar paravertebral route and in group
      CB, patients were given 1 ml/kg levobupivacaine caudally. Sevoflurane
      concentration was evaluated after induction and recorded during incision, sac
      traction and closure. Face, legs, activity, cry and consolability (FLACC) scores,
      heart rate, blood pressure and SpO2 were evaluated postoperatively. Only four
      (11.4%) patients in the PVB group needed rescue analgesic drugs compared to 12
      (34.3%) patients in the CB group (P = 0.044). Patients were given tramadol as
      rescue analgesia in the first four postoperative hours. No other supplemental
      analgesic drug was given apart from tramadol. FLACC scores were the same in the
      both groups. Parental satisfaction was significantly higher in the PVB group
      compared to the CB group (74.3 vs 40%, P = 0.01). This study has demonstrated
      that a single level single injection paravertebral block provides superior
      intraoperative and postoperative analgesia when compared to a caudal block for
      unilateral inguinal hernia repair.

PMID- 21970139
TI  - Cerebrospinal fluid cytology in patients undergoing combined spinal epidural
      versus spinal anaesthesia without an introducer.
AB  - The problem of tissue coring exists despite the availability of smaller gauge
      spinal needles with special tip designs. The aim of the study was to test the
      hypotheses that a) subarachnoid block given as a part of a combined spinal
      epidural intervention by needle-through-needle technique introduces a lesser
      number of epithelial cells into the subarachnoid space compared to isolated
      subarachnoid block, and b) after lumbar puncture, the initial few drops of
      cerebrospinal fluid from the spinal needle will have a higher number of
      epithelial cells than the subsequent sample. One hundred and seven patients of
      American Society of Anesthesiologists physical status I to III undergoing infra
      umbilical surgery were enrolled. Seven patients were excluded from the study and
      the rest divided into two groups to receive either combined spinal epidural
      anaesthesia (group A) or isolated subarachnoid anaesthesia, unaided by an
      introducer (group B). The two groups were compared for the presence of epithelial
      cells in cerebrospinal fluid. The initial four to six drops of cerebrospinal
      fluid (sample 1) were collected, the next four to six drops discarded and the
      following four to six drops (sample 2) collected. The incidence of coring was 96%
      in group A and 88% in group B (P = 0.142). The median (interquartile range)
      number of cells in group A, for samples 1 and 2 was 6 (3 to 12.5) and 6 (3 to
      10); and in group B, 3.5 (1 to 10) and 4 (1 to 8) respectively. Significant
      tissue coring was observed with both techniques. Discarding eight to 12 drops of
      cerebrospinal fluid did not help in reducing the epithelial cell load.

PMID- 21970140
TI  - 'Safe' methaemoglobin concentrations are a mortality risk factor in patients
      receiving inhaled nitric oxide.
AB  - Inhaled nitric oxide (iNO) can reduce pulmonary arterial hypertension and improve
      oxygenation in some patients with severe respiratory or heart failure. Despite
      this, iNO has not been found to improve survival. This study aimed to perform a
      local practice audit to assess the mortality predictors of critically ill
      patients who had received iNO as therapy for pulmonary hypertension and
      respiratory or heart failure. A retrospective audit in a single tertiary centre
      intensive care unit of patients receiving iNO was conducted between 2004 and
      2009. The indications for iNO use, comorbidities, severity of illness, organ
      function, oxygenation, Sequential Organ Failure Assessment scores, patterns of
      iNO use, adverse events and outcomes were reviewed. In 215 patients receiving
      iNO, improvement in oxygenation after one hour from iNO commencement did not
      predict either intensive care unit (P = 0.36) or hospital (P = 0.72) mortality.
      The independent risk factors for intensive care unit mortality were worsening
      Sequential Organ Failure Assessment scores within 24 hours of commencing iNO
      (adjusted odds ratio 1.07, 95% confidence interval 1.05 to 1.18), the Charlson
      Comorbidity Score (adjusted odds ratio 1.49, 95% confidence interval 1.16 to
      1.91) and the peak methaemoglobin concentration in arterial blood while receiving
      iNO (adjusted odds ratio 2.67, 95% confidence interval 1.42 to 4.96). Inhaled
      nitric oxide as salvage therapy for severe respiratory failure in critically ill
      patients is not routinely justified. Increased methaemoglobin concentration
      during iNO therapy, even when predominantly less than 3%, is associated with
      increased mortality.

PMID- 21970141
TI  - Compliance with processes of care in intensive care units in Australia and New
      Zealand--a point prevalence study.
AB  - There are indications that compliance with routine clinical practices in
      intensive care units (ICU) varies widely internationally, but it is currently
      unknown whether this is the case throughout Australia and New Zealand. A one-day
      point prevalence study measured the prevalence of routine care processes being
      delivered in Australian and New Zealand ICUs including the assessment and/or
      management of: nutrition, pain, sedation, weaning from mechanical ventilation,
      head of bed elevation, deep venous thrombosis prophylaxis, stress ulcer
      prophylaxis, blood glucose, pressure areas and bowel action. Using a sample of 50
      adult ICUs, prevalence data were collected for 662 patients with a median age of
      65 years and a median Acute Physiology and Chronic Health Evaluation II score of
      18. Wide variations in compliance were evident in several care components
      including: assessment of nutritional goals (74%, interquartile range [IQR] 51 to
      89%), pain score (35%, IQR 17 to 62%), sedation score (89%, IQR 50 to 100%); care
      of ventilated patients e.g. head of bed elevation > 30 degrees (33%, IQR 7 to
      62%) and setting weaning plans (50%, IQR 28 to 78%); pressure area risk
      assessment (78%, IQR 18 to 100%) and constipation management plan (43%, IQR 6 to
      87%). Care components that were delivered more consistently included nutrition
      delivery (100%, IQR 100 to 100%), deep venous thrombosis (96%, IQR 89 to 100%)
      and stress ulcer (90%, IQR 78 to 100%) prophylaxis, and checking blood sugar
      levels (93%, IQR 88 to 100%). This point prevalence study demonstrated
      variability in the delivery of 'routine' cares in Australian and New Zealand
      ICUs. This may be driven in part by lack of consensus on what is best practice in
      intensive care units, prompting the need for further research in this area.

PMID- 21970142
TI  - The impact of anaesthetic trainees on elective caesarean section procedural
      times: a prospective observational study.
AB  - Operating room efficiency is an important concern in hospitals today both in the
      public and private sectors. Currently, a paucity of literature exists to evaluate
      the impact of anaesthetic training on operating room efficiency in the Australian
      health system. At Monash Medical Centre, Clayton, private consultant operating
      sessions and public teaching operating sessions use the same operating theatres,
      nursing and technical staff. Consultant anaesthetists and obstetricians perform
      all tasks during private sessions, whereas anaesthetic and obstetric trainees
      perform many tasks during public sessions. In this prospective observational
      study, total case time, anaesthesia controlled time and the surgical time were
      measured for elective caesarean section under spinal anaesthesia in 59 patients
      (private consultant n = 29, public teaching n = 30). Increases in total case time
      (24 minutes, P < 0.001), anaesthesia controlled time (5.2 minutes, P < 0.015) and
      surgical time (19.25 minutes, P < 0.001) were observed in the public teaching
      group compared with the private consultant group. The participation of anesthetic
      trainees in caesarean sections results in a modest increase in anaesthetic
      controlled time of approximately five minutes per case or 16 minutes in an
      operative session with three cases scheduled. Elimination of anaesthetic
      'training' time does not allow scheduling of an extra elective caesarean section.
      Reduced operating theatre throughput is unlikely to be a consequence of training
      specialist anaesthetists in this clinical setting.

PMID- 21970143
TI  - Modification of Diamedica drawover anaesthetic equipment to facilitate
      introduction to an Australian teaching hospital.
AB  - We wanted to provide training in the use of drawover techniques and apparatus at
      an Australian teaching hospital. Equipment based on the Diamedica vaporiser was
      selected as it is suitable for use with sevoflurane. A lack of standards specific
      to drawover equipment from either anaesthetic professional bodies or national
      standards authorities hinders introduction of such equipment to Australian
      hospitals. Two systems were purchased, the Diamedica Portable Anaesthesia System
      and a Glostavent anaesthetic machine. Changes made to the equipment to increase
      its safety and to comply with Australian standards are described.

PMID- 21970144
TI  - A New Zealand based cohort study of anaesthetic trainees' career outcomes
      compared with previously expressed intentions.
AB  - Predicting workforce requirements is a difficult but necessary part of health
      resource planning. A 'snapshot' workforce survey undertaken in 2002 examined
      issues that New Zealand anaesthesia trainees expected would influence their
      choice of future workplace. We have restudied the same cohort to see if that
      workforce survey was a good predictor of outcome. Seventy (51%) of 138 surveys
      were completed in 2009 compared with 100 (80%) of 138 in the 2002 survey. Eighty
      percent of the 2002 respondents planned consultant positions in New Zealand. We
      found 64% of respondents were working in New Zealand (P < 0.01). We found that
      family ties were an important influence on the choice of country of residence for
      80% of New Zealand based respondents but only 40% of those living outside New
      Zealand agreed or strongly agreed with this statement (P < 0.01). Remuneration
      influenced country of residence for 76% of those living outside New Zealand but
      was important for only 2% of those resident in New Zealand (P < 0.01). Salaries
      in New Zealand were predominantly between NZ$150,000 and $200,000 while those
      overseas received between NZ$300,000 and $400,000. Of those that are resident in
      New Zealand, 84% had studied in a New Zealand medical school compared with 52% of
      those currently working overseas (P < 0.01). Our study shows that stated career
      intentions in a group do not predict the actual group outcomes. We suggest that
      'snapshot' studies examining workforce intentions are of little value for
      workforce planning. However we believe an ongoing program matching career
      aspirations against career outcomes would be a useful tool in workforce planning.

PMID- 21970145
TI  - Anaesthetic management of emergency caesarean section in a patient with seizures
      and likely raised intracranial pressure due to tuberculous meningitis.
AB  - We report the anaesthetic management of a term pregnant woman with active
      tuberculous meningitis, who had experienced seizures, had signs of raised
      intracranial pressure and required emergency caesarean section. Peripartum
      anaesthetic management of a patient with tuberculous meningitis is a rare event.

PMID- 21970146
TI  - Extracorporeal membrane oxygenation in a patient with stress-induced
      cardiomyopathy after caesarean section.
AB  - Stress-induced cardiomyopathy is an acute cardiac syndrome mimicking ST-segment
      elevation myocardial infarction and is characterised by transient left
      ventricular dysfunction in the absence of obstructive coronary artery disease.
      Caesarean delivery is associated with intense emotional and physical stress,
      which may precipitate stress-induced cardiomyopathy mimicking acute myocardial
      infarction. We report a case of a woman who was supported with extracorporeal
      membrane oxygenation for acute heart failure and severe pulmonary oedema, which
      may have resulted from stress-induced cardiomyopathy in the early postpartum
      period following caesarean delivery.

PMID- 21970148
TI  - Adherent transversus abdominis plane catheter.

PMID- 21970147
TI  - Computed tomography changes of alveoli and airway collapse after laryngospasm.
AB  - An eight-month-old girl underwent a computed axial tomographic study of the chest
      and neck for investigation of expiratory stridor. Following the scout scan,
      severe laryngospasm developed. While no cause for the laryngospasm was found, the
      computed axial tomographic chest study showed marked changes in the lungs
      consistent with absorption atelectasis which we postulate occurred secondary to
      laryngospasm.

PMID- 21970149
TI  - Vocal cord palsy: an unusual complication of paravertebral block.

PMID- 21970150
TI  - A simple method for blocking the deep cervical nerve plexus using an ultrasound
      guided technique.

PMID- 21970151
TI  - What makes metalware single-use?

PMID- 21970152
TI  - Awareness during cardiac surgery--a single-centre prospective clinical audit of
      1060 patients.

PMID- 21970153
TI  - Mediastinitis after the use of the LMA-Supreme.

PMID- 21970154
TI  - The Episure loss-of-resistance syringe.

PMID- 21970155
TI  - The possible role of cranio-cervical trauma and abnormal CSF hydrodynamics in the
      genesis of multiple sclerosis.
AB  - UPRIGHT Multi-Position MR scanning has uncovered a key set of new observations
      regarding Multiple Sclerosis (MS), which observations are likely to provide a new
      understanding of the origin of MS. The new findings may also lead to new forms of
      treatment for MS. The UPRIGHT MRI has demonstrated pronounced anatomic pathology
      of the cervical spine in five of the MS patients studied and definitive cervical
      pathology in the other three. The pathology was the result of prior head and neck
      trauma. All eight MS patients entered the study on a first come first serve basis
      without priority, and all but one were found to have a history of serious prior
      cervical trauma which resulted in significant cervical pathology. The cervical
      pathology was visualized by UPRIGHT MRI. Upright cerebrospinal fluid (CSF)
      cinematography and quantitative measurements of CSF velocity, CSF flow and CSF
      pressure gradients in the upright patient revealed that significant obstructions
      to CSF flow were present in all MS patients. The obstructions are believed to be
      responsible for CSF "leakages" of CSF from the ventricles into the surrounding
      brain parenchyma which "leakages" can be the source of the MS lesions in the
      brain that give rise to MS symptomatology. The CSF flow obstructions are believed
      to result in increases in intracranial pressure (ICP) that generate "leakages" of
      the CSF into the surrounding brain parenchyma. In all but one MS patient,
      anatomic pathologies were found to be more severe in the upright position than in
      the recumbent position. Similarly, CSF flow abnormalities were found to be more
      severe in the upright position than in the recumbent position in all but one MS
      patient. Images of the MS patient anatomic pathologies and CSF flow abnormalities
      are provided with comparison images from normal examinees in Figures 1-15.

PMID- 21970156
TI  - Truth in basic biomedical science will set future mankind free.
AB  - It is self-evident that continued wellbeing and prosperity of our species in time
      to come depends upon a steady supply of major scientific and technologic
      innovations. However, major scientific and technical innovations are rare. As a
      rule, they grow only in the exceptionally fertile minds of men and women, who
      have fully mastered the underlying basic sciences. To waken their interest in
      science at an early critical age and to nurture and enhance that interest
      afterward, good textbooks at all level of education that accurately portray the
      relevant up-to-date knowledge are vital. As of now, the field of science that
      offers by far the greatest promise for the future of humanity is the science of
      life at the most basic cell and below-cell level. Unfortunately, it is precisely
      this crucial part of the (standardized) biological textbooks for all high schools
      and colleges in the US and abroad that have become, so to speak, fossilized. As a
      result, generation after generation of (educated) young men and women have been
      and are still being force-fed as established scientific truth an obsolete
      membrane (pump) theory, which has been categorically disproved half a century ago
      (see Endnote 1.) To reveal this Trojan horse of a theory for what it really is
      demands the concerted efforts of many courageous individuals especially young
      biology teachers who take themselves and their career seriously. But even the
      most courageous and the most resourceful won't find the task easy. To begin with,
      they would find it hard to access the critical scientific knowledge, with which
      to convert the skeptic and to rally the friendly. For the wealth of mutually
      supportive evidence against the membrane (pump) theory are often hidden in
      inaccessible publications and/or in languages other than English. To overcome
      this seemingly trivial but in fact formidable obstacle and to reveal the beauty
      and coherence of the existing but untaught truth, I put together in this small
      package a collection of the major clenching theoretical and experimental
      findings. These findings will remove the last trace of uncertainty about the
      total disproof of the membrane theory. In addition, I have also included an
      introduction of the association-induction hypothesis, which is the one and only
      unifying theory of the living cell that has survived and unwaveringly grown more
      comprehensive and powerful after more than half of a century of worldwide
      testing.

PMID- 21970157
TI  - Hydrazide drugs that inhibit growth and proliferation of tuberculosis bacteria.
AB  - Four hydrazide drugs are shown to effectively and strongly inhibit the growth of
      Mycobacterium bovis BCG. The four compounds were found to be comparable to
      isoniazid for extent of growth inhibition. Similar to isoniazid, the four drug
      designs have a hydrazide functional group (-C(O)NHNH2) that replaces a former
      carboxyl group (-C(O)OH). Important pharmaceutical properties were determined for
      all drugs including Log P, polar surface area, water solubility, and violations
      of the Rule of 5. Values of Log P for A, B, C, D, and isoniazid were determined
      to be 1.08, 1.26, 1.26, 1.06, and -0.70, respectively. The polar surface area for
      drugs A, B, and C were calculated to be 55.12 Angstroms2, which is a value that
      suggests these drugs will effectively penetrate the central nervous system for
      targeting tuberculosis that infects that anatomical region. All drug designs and
      isoniazid show zero violations of the Rule of 5 indicating favorable drug
      bioavailability. Water solubility for all drugs varies from 1074 milligrams/liter
      to 16690 milligrams/liter. Growth inhibition of tuberculosis bacteria was greater
      than 50% for all novel drugs at concentrations of 62.5 micrograms/milliliter and
      higher. Cluster analysis determined that isoniazid is distinct from all new drug
      designs. For molecular descriptors, molecular volume is directly correlated to
      formula weight and polar surface area (Pearson r > 0.8800). The four novel drug
      designs show substantial efficacy for the clinical treatment of tuberculosis.

PMID- 21970158
TI  - Artifacts of electron microscopy in cells.
AB  - With the esception of the Gollgi apparatus, the main artifacts were first seen by
      electron microscopy. Those detected over the last 30 years, and the reasons for
      which they are artifacts, are summarised.

PMID- 21970159
TI  - Speed-dependent emission of air pollutants from gasoline-powered passenger cars.
AB  - In Korea emissions from motor vehicles are a major source of air pollution in
      metropolitan cities, and in Seoul a large proportion of the vehicle fleet is made
      up of gasoline-powered passenger cars. The carbon monoxide (CO), hydrocarbons
      (HC), oxides of nitrogen (NOx) and carbon dioxide (CO2) contained in the exhaust
      emissions from 76 gasoline-powered passenger cars equipped with three-way
      catalysts has been assessed by vehicle speed, vehicle mileage and model year. The
      results show that CO, HC, NOx and CO2 emissions remained almost unchanged at
      higher speeds but decreased rapidly at lower speeds. While a reduction in CO, HC
      and NOx emissions was noticeable in vehicles of recent manufacture and lower
      mileage, CO2 emissions were found to be insensitive to vehicle mileage, but
      strongly dependent on gross vehicle weight. Lower emissions from more recent
      gasoline-powered vehicles arose mainly from improvements in three-way catalytic
      converter technology following strengthened emission regulations. The correlation
      between CO2 emission and fuel consumption has been investigated with a view to
      establishing national CO2 emission standards for Korea.

PMID- 21970160
TI  - Adsorption of basic dye from wastewater using raw and activated red mud.
AB  - Red mud, an industrial by-product generated during the processing of bauxite ore,
      was investigated as an inexpensive and effective adsorbent for the adsorption of
      methylene blue from aqueous solution. Chemical and heat treatments were applied
      to the raw red mud. The effects of contact time, adsorbent amount, pH,
      temperature and initial dye concentration were investigated. The adsorption
      isotherm and kinetics of the raw and activated red mud were studied. Freundlich,
      Temkin and Dubinin-Radushkevich isotherms were obtained using concentrations of
      methylene blue ranging from 10 to 70 mg/L. The results indicated that the Dubinin
      Radushkevich model provides the best correlation of the experimental data. The
      adsorption rate data were analysed according to the pseudo-first order kinetic,
      pseudo-second order kinetic, intraparticle diffusion kinetic and Elovich kinetic
      models. The pseudo-second order kinetic was the best fit kinetic model for the
      experimental data.

PMID- 21970162
TI  - Aerobic, thermophilic, semi-continuous treatment of cattle slurry with whey and
      jam.
AB  - Aerobic thermophilic treatment (ATT) of cattle slurry and industrial food waste
      (whey and jam) was conducted semi-continuously, with the aim of developing the
      ATT process. We could improve the final products in terms of hygiene,
      environmental effects and heat production. In addition we tried to solve the
      foaming problem mechanically. The trial was done by using a farm-scale bioreactor
      with a total volume of 12 m3 and a theoretical retention time of some 15 days.
      Temperature increased to 55 degrees C at the end of the trial. The process could
      be an efficient method for the control of foam. Using the waste food (whey and
      jam) improved the process.

PMID- 21970161
TI  - Microwave preparation of raw vermiculite for use in removal of copper ions from
      aqueous solutions.
AB  - This study sought to determine optimum conditions for the microwave exfoliation
      of raw vermiculite and examined the removal characteristics of copper ions from
      water by the processed vermiculite. When 100 g of raw vermiculite was irradiated
      at 440 W for 330 s, 66% of the raw vermiculite was exfoliated. The dry density
      and specific surface area of the exfoliated vermiculite were 0.28 g/cm3 and 54.6
      m2/g, respectively. When considering the dry density (2.78 g/cm3) and specific
      surface area (11.1 m2/g) of the raw vermiculite, microwave irradiation resulted
      in an approximate 10 times expansion and a five-fold increase in specific surface
      area. Serial batch tests were conducted to determine the removal characteristics
      of the exfoliated vermiculite for copper ions in aqueous solutions. Copper was
      most effectively removed by exfoliated vermiculite with an initial pH of 5.
      Exfoliated vermiculite at this pH also produced the highest first-order rate
      constants and instantaneous partition coefficient. These results indicate that
      exfoliated vermiculite can be prepared by microwave irradiation instead of
      conventional heat processes for use as a copper ion adsorbent.

PMID- 21970163
TI  - Removal of arsenic from aqueous environments by native and chemically modified
      biomass of Aspergillus niger and Neosartorya fischeri.
AB  - Arsenic removal from aqueous solutions by biomass of two fungal strains,
      Aspergillus niger and Neosartorya fischeri, was assessed. The biosorption
      capacity of fungal biomass was studied within the As(V) concentration range of
      approximately 0.2 to 5.0 mg L(-1) at two different pH values (pH 5 and 7). With
      increasing initial arsenic concentration, the biosorption capacity of both fungal
      strains increased almost linearly and achieved the sorption capacity of 0.317 and
      0.124 mg g(-1) for biomass of N. fischeri and A. niger, respectively. The effect
      of biomass treatment with FeCl3 and HCI on As(III) and As(V) uptake was also
      studied. The optimum biosorption pH as well as the effect ofbiomass treatment was
      found to be dependent on the fungal strain used. Treatment with FeCl3 and HCl did
      not result in any significant increase in arsenic uptake. To the contrary,
      treatment with ferric oxyhydroxide was found to be very effective and virtually
      100% of the arsenic was removed from the samples of contaminated natural water.

PMID- 21970164
TI  - Effect of temperature on microbial population and performance of an aerobic
      thermophilic reactor treating cattle slurry and waste food.
AB  - This study was carried out to quantify and identify the presence of somatic
      coliphages, RNA coliphages, sulphite-reducing clostridia, Clostridium
      tyrobutyricum or its related clostridia, faecal coliforms, enterococci and
      heterotrophs in a mixture of cattle slurry and waste food (whey and jam) that had
      undergone aerobic thermophilic treatment (ATT). We also investigated the
      influence of different factors, including pH, COD, temperature, odour removal,
      addition of waste food (whey and jam) and nitrogen losses, on the long-term ATT
      process. The processes were conducted semi-continuously with retention time of
      five days and with the waste food and slurry mixture (1:4) being added daily into
      the reactor. The experiments lasted seven days for each thermophilic temperature
      (50, 60 and 70 degrees C). Our work showed that, at the higher temperature of the
      ATT operation, the number of microorganisms declined much more rapidly than at
      the lower temperature and the final product was hygienically safe. The use of
      waste food (whey and jam) was beneficial because it buffered pH.

PMID- 21970165
TI  - Effect of carrier composition on 2,6-dimethylaniline degradation in aqueous
      solution by fluidized-bed Fenton process.
AB  - The fluidized-bed Fenton process is an alternative process that decreases iron
      sludge from the Fenton reaction by using carriers to crystallize iron on to the
      surface of the carrier. In this study, the target compound is 2,6
      dimethylaniline, which is a carcinogen and difficult to degrade. This study
      examined the effect of different carriers on the degradation of 2,6
      dimethylaniline by a fluidized-bed Fenton process. The six carriers were alumina
      dioxide (Al2O3), silica dioxide (SiO2), and black, white, brown and coloured
      gravels. The results revealed that differences in the composition of elements and
      the structures of each carrier have different effects on the oxidation of 2,6
      dimethylaniline. The carriers containing Ca were not suitable for use in the
      fluidized-bed Fenton process. In contrast, Al2O3 and SiO2 were more efficient at
      removing 2,6-dimethylaniline, and the pH value was almost stable. Moreover, 2,6
      dimethylanililne removal efficiency of Al2O3 was higher compared with the other
      carriers. Therefore, in this study, Al2O3 was an optimum carrier for the
      oxidation of 2,6-dimethylaniline.

PMID- 21970166
TI  - Phanerochaete chrysosporium IBL-03 secretes high titers of manganese peroxidase
      during decolorization of Drimarine Blue K2RL textile dye.
AB  - A novel indigenous strain, Phanerochaete chrysosporium IBL-03, with high
      manganese peroxidase (MnP) activities was used for decolorization of a reactive
      textile dye, Drimarine Blue K2R, which is used extensively in textile units of
      Pakistan. The initial experiment was run for seven days with 0.01% (w/v) dye
      solution prepared in Kirk's basal nutrient medium. Samples were removed after
      every 24 h and the extent of dye decolorization was determined at lambda(max) of
      the dye. The study revealed that P. chrysosporium caused 65% decolorization of
      Drimarine Blue K2RL in seven days. By process optimization, 97% colour removal
      could be achieved in three days using 0.005% (w/v) Drimarine Blue K2RL solution
      at pH 4.0 and 30 degrees C in defined Kirk's medium with 0.9% (w/v) molasses and
      0.2% (w/v) ammonium dihydrogen phosphate added as carbon and nitrogen sources,
      respectively. Manganese peroxidase was found to be the major enzyme (560 IU/mL)
      involved in dye decolorization of Drimarine Blue K2RL by P. chrysosporium. The
      dye adsorption studies showed that the dye initially adsorbed on fungal mats
      disappeared later on, possibly by the action of MnP secreted by the fungus in
      secondary metabolism.

PMID- 21970167
TI  - Textile wastewater treatment using a UF hollow-fibre submerged membrane
      bioreactor (SMBR).
AB  - The objective of this study was to investigate the performance of a laboratory
      scale submerged membrane bioreactor (SMBR) system for the treatment of synthetic
      textile wastewater containing disperse red dye. The SMBR system was run
      aerobically in a continuous flow mode at five different hydraulic retention times
      (HRTs) of 24,18,14.4,11.28 and 8.4 h respectively, with an average permeate flux
      of 20 L/(m2 x h). The performance of the system was not adversely affected by
      decreased HRT and the consequent rise in the food/microorganism ratio (0.07 to
      0.14 g BOD/(g SS x d)) and organic loading rate (OLR: 0.4 to 1.24 BOD kg/(m3 x
      d)). The average removal rate for COD, BOD and colour were 92.33%, 93.69% and
      91.36%, respectively. To maintain a stable flux and prevent fouling, the membrane
      was covered with a cylindrical wire-mesh cage, and routine chemical backwashing
      and chemical cleaning procedures were adapted. Transmembrane pressure increased
      from 29.47 to 58.42 kPa (0.29 to 0.58 bar) during each run of HRT. The results
      indicated that synthetic textile wastewater could be treated very effectively by
      the SMBR system.

PMID- 21970168
TI  - Landfill leachate characterization for simulation of biological treatment with
      Activated Sludge Model No. 1 and Activated Sludge Model No. 3.
AB  - Landfill leachates can be characterized correctly in terms of Activated Sludge
      Model No. 1 (ASM1) and Activated Sludge Model No. 3 (ASM3) variables. The
      wastewater characterization of leachate from a Luxembourg landfill was based on a
      physical-chemical method combined with a BOD analysis for the COD fractions and
      on standard analysis for forms of nitrogen. The results show important
      differences compared with municipal wastewater. High amounts of organic matter
      with low biodegradability were found, as well as a high concentration of ammonium
      nitrogen. Based on average values, a generic ASM characterization is proposed for
      landfill leachates. It can be directly employed in the early stages of the
      simulation of landfill leachate treatment with activated sludge models.

PMID- 21970169
TI  - Leaching behaviour of bisphenol A from municipal solid waste under landfill
      environment.
AB  - With a preliminary insight into the source and leaching behaviour ofbisphenol A
      (BPA) from municipal solid wastes (MSW), five kinds of plastic and four kinds of
      paper materials were leached by distilled water. Polyvinyl chloride (PVC) waste
      was found to have the highest BPA content of 12.1 microg x g(-1) and leachability
      of 34.7% in distilled water, while cardboard with relatively low BPA content also
      showed a high ratio of leaching (53.6%). Fresh leachate and leachates from a
      landfill of age 1.5 and 10 years were adopted as leachants for the PVC plastic
      and cardboard to simulate the leaching behaviour of BPA under a landfill
      environment. The enhancement of BPA leachability in the 10-year leachate compared
      with distilled water was higher than that in the other two leachates due to its
      basic pH and high content of humic organic matters. Meanwhile, the enhancement of
      BPA leachability by the fresh leachate was higher than that by the 1.5-year
      leachate, possibly due to the presence of small molecules such as volatile fatty
      acids, amino acids, etc. The paper waste was not only a minor origin of BPA
      leaching, but also a controlling factor in retarding BPA transformation. The BPA
      sorption K(f) value of the cardboard in the Freundlich equation was 0.2224 mg(1
      n)) x L(n) x g(-1) (n = 0.7680), higher than that obtained in sorption
      experiments by natural organic adsorbents such as sediment. It suggested that the
      presence of paper with a high sorption capacity in MSW will restrain BPA
      transport and bioavailability in landfills.

PMID- 21970170
TI  - Effects of Mo(VI) on phototrophic hydrogen production by Rhodobacter sphaeroides.
AB  - Effects of Mo(6+) concentration on phototrophic hydrogen production of
      Rhodobacter sphaeroides were investigated using lactate as the sole carbon
      source. Results showed that an increase of Mo(6+) from nil to 1000 microg l(-1)
      led to increases in hydrogen yield, maximum production rate, conversion
      efficiency, biomass yield and lactate removal. At 100 microg-Mo l(-1), the
      maximum rate was 12.0 ml h(-1) with a conversion efficiency of 36.1%, the cell
      yields were 1.11 g-cell g(-1) -lactate and 2.4 g-cell g(-1)-TOC removed. Further
      increase of Mo(6+) improved hydrogen production only marginally. Degradation of
      lactate by R. sphaeroides produced not just hydrogen but also acetate, butyrate,
      i-valerate, i-caproate, hexanoate and some unidentified organic intermediates,
      but did not produce propionate and alcohols. Nitrogenase activity, as measured by
      the acetylene reduction method, had no clear correlation with either Mo(6+)
      concentration or hydrogen yield.

PMID- 21970171
TI  - Oxidation of polyaromatic hydrocarbons in systems containing water miscible
      organic solvents by the lignin peroxidase of Gleophyllum striatum MTCC-1117.
AB  - Lignin peroxidase has been purified to homogeneity using a process of
      concentration by ultrafiltration and anion exchange chromatography on
      diethylaminoethyl (DEAE) cellulose from the liquid culture filtrate of the brown
      rot fungi Gleophyllum striatum MTCC-1117. The molecular mass of the purified
      enzyme is 43 kDa as determined by sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE) analysis. The K(m) values for the enzyme using
      veratryl alcohol, hydrogen peroxide and n-propanol were 66 microM, 82 microM and
      476 microM, respectively. The pH and temperature optima of the enzyme were 2.8
      and 25 degrees C, respectively. The enzyme is completely inhibited by 20% of the
      water miscible organic solvents acetone dioxane, diethylether, acetonitrile and
      dimethylformamide. The lignin peroxidase oxidizes polycyclic aromatic
      hydrocarbons pyrene, acenaphthene, anthracene, dibenothiophene and 9-methyl
      anthracene.

PMID- 21970172
TI  - Development of sewage sludge-based synthetic aggregates for containerized
      ornamentals.
AB  - Potential utilization of synthetic aggregates (SAs) developed from sewage sludge
      (SS) as a component of containerized media for French marigold (Tagetes patula)
      cultivation as a peat substitution was investigated in this study. The six
      different containerized media utilized were: peat only, SA 20%: peat 80%, SA 40%:
      peat 60%, SA 60%: peat 40%, SA 80%: peat 20% and SA only. The physical and
      chemical characteristics of all media were determined. SA-based media showed
      higher pH, electrical conductivity (EC), bulk density, particle density and
      nutrient contents (N, P, Ca and Mg) compared to peat media. The highest plant
      length, number of flowers per plant, shoot fresh weight, shoot dry weight, root
      length, root fresh weight and root dry weight obtained from the medium having SA
      40%: peat 60% increased by 13.69%, 23.53%, 41.46%, 58.95%, 2.43%, 39.09% and
      21.68%, respectively, compared to the peat control. The addition of 60% and 100%
      of SAs to the growth media gave the lowest growth and yield parameters compared
      to the peat control due to their high EC and pH. Plant tissues obtained from
      media with added SAs showed increased N, P, Ca and Mg contents compared to plant
      tissues obtained from peat media. Media with added SAs did not significantly
      increase concentrations of Cu, Cd, Cr and Pb in plant tissues but the Zn
      concentration was significantly increased. SA addition to media did not pose any
      phytotoxicity risks in French marigold plants. SAs can be suggested as viable
      potting media components to substitute for the widely used and more expensive
      peat utilized in horticulture.

PMID- 21970173
TI  - Study of canal sediments contaminated with heavy metals: fungal versus bacterial
      bioleaching techniques.
AB  - Filamentous fungi and lithotrophic bacteria were used to leach heavy metals from
      dredged sediments in semi-pilot scale air-lift bioreactors. A preliminary physico
      chemical characterization of the sediments comprising a sequential extraction
      study revealed their high metallic contamination and a predominant association of
      the metals with sulphides and organic matter. The mobility of heavy metals from
      sediments was ranked by decreasing order as follows: Mn > Zn > Cd > Cu > Pb. The
      conditions that favoured the solubilization of heavy metals by filamentous fungi
      turned out to be also favourable for the activity of the sediment organotrophic
      bacteria. The latter produced organic acids under temporary hypoxic conditions
      and resulted in the solubilization of 77% of manganese, 44% of zinc, 12% of
      copper, and less than 2% of cadmium or lead. In general, the fungal organotrophic
      treatments were limited to the relatively mobile metals due to the weak nature of
      the organic acids produced and to their microbial consumption under limited
      saccharose conditions. The lithotrophic treatments yielded higher solubilization
      results than the organotrophic experiments. Sulphur resulted in a faster, and for
      some metals such as copper and cadmium, in better bioleaching results compared
      with reduced iron or with a combination of reduced iron and sulphur. The
      bioleaching percentages varied between 72 and 93% for cadmium, copper, manganese
      and zinc, except for lead because of the poor solubility of lead sulphate. The
      sediment's lithotrophic bacteria acidified the matrix through sulphur oxidation,
      and leached both loosely and tightly bound metals.

PMID- 21970174
TI  - Competitive adsorption of phenolic compounds from aqueous solution using sludge
      based activated carbon.
AB  - Preparation of activated carbon from sewage sludge is a promising approach to
      produce cheap and efficient adsorbent for pollutants removal as well as to
      dispose of sewage sludge. The first objective of this study was to investigate
      the physical and chemical properties (BET surface area, ash and elemental
      content, surface functional groups by Boehm titration and weight loss by
      thermogravimetric analysis) of the sludge-based activated carbon (SBAC) so as to
      give a basic understanding of its structure and to compare to those of two
      commercial activated carbons, PICA S23 and F22. The second and main objective was
      to evaluate the performance of SBAC for single and competitive adsorption of four
      substituted phenols (p-nitrophenol, p-chlorophenol, p-hydroxy benzoic acid and
      phenol) from their aqueous solutions. The results indicated that, despite
      moderate micropore and mesopore surface areas, SBAC had remarkable adsorption
      capacity for phenols, though less than PICA carbons. Uptake of the phenolic
      compound was found to be dependent on both the porosity and surface chemistry of
      the carbons. Furthermore, the electronegativity and the hydrophobicity of the
      adsorbate have significant influence on the adsorption capacity. The Langmuir and
      Freundlich models were used for the mathematical description of the adsorption
      equilibrium for single-solute isotherms. Moreover, the Langmuir-Freundlich model
      gave satisfactory results for describing multicomponent system isotherms. The
      capacity of the studied activated carbons to adsorb phenols from a multi-solute
      system was in the following order: p-nitrophenol > p-chlorophenol > PHBA >
      phenol.

PMID- 21970175
TI  - Enhanced ammonia nitrogen removal using consistent ammonium exchange of modified
      zeolite and biological regeneration in a sequencing batch reactor process.
AB  - Utilizing preferential ion exchange of the modified zeolite, the zeo-sequencing
      batch reactor (SBR) is recommended for a new nitrogen removal process. In this
      study, natural zeolite was modified by sodium chloride to enhance sorption
      capacity for ammoniacal nitrogen. The untreated and treated zeolite was
      characterized by XPS and XRD techniques. The sorption isotherm tests showed that
      equilibrium sorption data were better represented by the Langmuir model than by
      the Freundlich model. Treatment of natural zeolite by sodium chloride increased
      the sorption capacity for ammoniacal nitrogen removal from aqueous solutions. As
      a result of the continuous bioregeneration of ammonium saturated zeolite-floc in
      the SBR, the nitrogen removal efficiency of the zeo-SBR was relatively ideal.
      Scanning electron microscopy results showed that microbes were abundant in the
      zeo-SBR process.

PMID- 21970176
TI  - Evaluation of the hazardous impact of landfill leachates by toxicity and
      biodegradability tests.
AB  - The aim of our research was to assess the ecotoxicity and biodegradability of
      leachates originating from two parts of a municipal landfill before and after
      biological treatment in the existing treatment plant. Biotests represent
      important tools for adequate environmental characterization of landfill leachates
      and could be helpful in reliable assessment and monitoring of the treatment plant
      efficiency. For ecotoxicity testing of landfill leachate before and after
      biological treatment, different organisms were chosen: the bacteria Vibrio
      fischeri, a mixed culture of activated sludge, duckweed Lemna minor, white
      mustard Sinapis alba, brine shrimp Artemia salina, and water flea Daphnia magna.
      For assessment of biodegradability, the method for determination of oxygen demand
      in a closed respirometer was used. The investigated leachates were heavily
      polluted, and in some cases, effluent limits were exceeded even after treatment.
      Results indicated that toxicity tests and physico-chemical parameters determined
      before and after treatment equivalently assess the efficiency of the existing
      treatment plant. However, the investigated leachates showed higher toxicity to
      Daphnia magna and especially to Lemna minor in contrast to Vibrio fischeri and
      Artemia salina (neither was sensitive to any of the leachates). No leachates were
      readily biodegradable. Experiments confirmed that the battery of toxicity tests
      should be applied for more comprehensive assessment of landfill leachate
      treatment and for reliable assessment of the treated leachate's subsequent
      environmental impact. It was confirmed that treated leachate, in spite of its
      better physico-chemical characteristics, still represents a potential
      environmental risk and thus should not be released into the environment.

PMID- 21970177
TI  - The effect of global velocity gradient on the character and filterability of
      aggregates formed during the coagulation/flocculation process.
AB  - This paper describes the influence of the global velocity gradient G on the
      properties of aggregates formed during the coagulation/flocculation process. The
      methods of image and fractal analysis were used to determine aggregate size and
      structure, respectively. The influence of these aggregate properties on
      separation using depth filtration is also described. Experiments were conducted
      in a pilot plant operation. The suspension was formed in a flow mixing tank with
      global velocity gradients ranging from 28.4-307.2 s(-1) and ferric sulphate used
      as a coagulant. Filtration velocities were 3 and 6 m h(-1). Predictably, it was
      shown that the aggregate size decreased with increasing global velocity gradient
      G. Furthermore it was demonstrated that, with increasing G, the aggregates became
      more compact and regular (the D2 fractal dimension increased) and the suspension
      became more homogeneous in size. The aggregates with the smallest diameter and
      highest D2 fractal dimension displayed the best filterability, i.e. penetrated
      throughout the full depth of the filter bed and generated a minimum pressure
      drop.

PMID- 21970178
TI  - Fate and removal of permethrin by conventional activated sludge treatment.
AB  - The fate and removal of permethrin during conventional wastewater treatment were
      evaluated at pilot-plant scale at different concentrations of mixed liquor
      suspended solids (MLSS) and, hence, different solids retention times (SRT). At
      feed concentrations of 0.26-0.86 microg L(-1), the permethrin was removed by
      primary treatment at an efficiency rate of 37%, similar to previously reported
      data, and from 40% to 83% for secondary treatment, decreasing with decreasing
      SRT. Comparable ranges, from 37% up to 98%, have been reported for
      micropollutants with similar physicochemical properties to permethrin, such as
      galaxolide and tonalide. Little difference in removal was noted between the
      medium and low MLSS concentrations trials, the main difference in treated
      effluent permethrin concentration arising on changing from high to medium MLSS
      levels. This was attributed to the limited acclimatization period employed in
      these two trials, leading to higher levels of soluble organic matter in the
      treated water, with which the permethrin appeared to be associated.

PMID- 21970179
TI  - Anaerobic bioremediation of marine sediment artificially contaminated with
      anthracene and naphthalene.
AB  - The bioremediation of marine sediments contaminated with naphthalene and
      anthracene was studied under anaerobic conditions to investigate the enhancing
      effect of a biostimulating agent (Tween 80, silicone oil, pig dung and NPK
      fertilizer) on the rate of degradation. Sediment samples were amended with the
      biostimulating agent (alone or in combination). The results showed that all the
      tested agents, applied individually to the sediments, increased the rate of
      anthracene and naphthalene degradation, with the pig dung having the greatest
      effect. The biodegradation data were fitted to a pseudo-first-order kinetic
      model, from which the biodegradation rate constant, as a measure of the
      enhancement of degradation rate by the biostimulators, was estimated. The rate
      constant values were consistently higher for the sediments treated with
      individual stimulators, or a combination of them, than for the untreated
      sediment. The contaminated sediment treated with the combination of Tween 80 and
      pig dung exhibited the highest biodegradation rate. The results indicated that
      the effect of various biostimulating agents, in combination or alone, on
      enhancing the degradation rate of anthracene and naphthalene can be arranged in
      the following order: Tween 80 + pig dung > silicone oil + pig dung > Tween 80 +
      NPK fertilizer > silicone oil + NPK fertilizer > pig dung > NPK fertilizer >
      Tween 80 > silicone oil. The addition of biostimulators increased the
      biodegradation potential of the intrinsic microbial populations; thus, these
      results will contribute to the development of new strategies for in situ
      bioremediation of anoxic sediments contaminated with polycyclic aromatic
      hydrocarbons

PMID- 21970180
TI  - Occurrence, characterization and insecticidal activity of Bacillus thuringiensis
      strains isolated from argan fields in Morocco.
AB  - Soils collected from five locations in the argan forest (an endemic plant) in
      Morocco were used to form the first collection of Bacillus thuringiensis (Bt)
      strains from this area (58 strains). Here we found that the argan forest is a
      major source of Bt, as 90.62% of the samples contained Bt strains. These strains
      produced mainly spherical or irregular crystals that in some cases remained
      adhered to the spore after cell lysis. There was no strain producing bipyramidal
      crystals, suggesting the absence of strains bearing crv1 genes. This was
      confirmed by PCR analysis using eight primer pairs that can potentially detect 13
      different groups of cry and cyt genes. Strains containing cry7/8 were the most
      abundant (25.53%), followed by strains harbouring cry9A (14.89%), cry11 (8.51%)
      and cry4 (4.25%). The mixtures of spores and crystals as well as culture
      supernatants were assayed for toxicity towards Ceratitis capitata (Medfly),
      showing up to 30% mortality. Our findings suggest that the argan region is a
      suitable target for future and wider screening programmes looking for strains
      bearing toxins or combinations of them to develop more efficient Bt-based
      formulates.

PMID- 21970181
TI  - Precipitation of dissolved sulphide in pulp and paper mill wastewater by
      electrocoagulation.
AB  - The precipitation of dissolved sulphide ions by electrocoagulation was studied at
      laboratory scale using pulp and paper mill wastewaters. Concentrations of
      dissolved organic carbon and phosphorus were analysed before and after the
      electrocoagulation process to examine the suitability of the process for
      treatment of sulphide odour from pulp and paper mill wastewater. The
      electrochemical cell used in this study was constructed from monopolar dissolving
      iron electrodes. The dissolved iron concentration was directly proportional to
      the applied electric charge (C/L) at the tested current densities.
      Electrochemically produced ferrous iron (Fe2+) precipitated dissolved sulphide
      ions efficiently. Electricity consumption of the treatment was 4-8 C/mg S(2-)
      while iron consumption was 1.1-2.2 mg/mg S(2-) during the initial phase of the
      sulphide precipitation when the applied electric charge was 10-60 C/L. When 60
      C/L was applied, 88% of dissolved sulphides and 40% of phosphorus was
      precipitated. The reduction in DOC was low during the sulphide precipitation.
      According to these results, electrocoagulation can precipitate dissolved
      sulphides effectively and thereby reduce sulphide odours of pulp and paper mill
      wastewaters.

PMID- 21970182
TI  - Synergism effects for Escherichia coli inactivation applying the combined ozone
      and chlorine disinfection method.
AB  - Water disinfection assays were carried out using ozone and chlorine in non
      sequential steps--the individual method--and in sequential steps--the combined
      ozone/chlorine method. Escherichia coli strain ATCC 11229 was used as the
      indicator microorganism. For the assays using the individual method, the applied
      dosages of ozone were 2.0, 3.0 and 5.0 mg/L, and 2.0 and 5.0 mg/L of chlorine
      were used. For the assays applying the combined method, the dosages (dosage
      combination) were, in mg/L: 2.0 O3 + 2.0 Cl, 3.0 O3 + 2.0 Cl2, 5.0 O3 + 2.0 Cl2
      and 2.0 O3 + 5.0 Cl2. The applied contact times were 5, 10, 15 and 20 minutes for
      the individual method as well as for the combined method. For all used dosages
      and contact times, E. coli inactivation was superior to the inactivation obtained
      in the individual method, indicating the occurrence of synergism for E. coli
      inactivation in the combined method.

PMID- 21970183
TI  - Determination of endocrine-disrupting compounds in waters from Rio das Velhas,
      Brazil, by liquid chromatography/high resolution mass spectrometry (ESI-LC-IT
      TOF/MS).
AB  - Some organic microcontaminants, known as endocrine-disrupting compounds (EDC),
      are frequently found in surface waters and are of concern because of their
      ability to alter the normal functioning of the endocrine system. In this study
      five of these EDCs (estradiol, ethynylestradiol, bisphenol A, nonylphenol and
      diethylphthalate) in surface water samples, collected at the upper part of Rio
      das Velhas river (located between Ouro Preto and Nova Lima, Minas Gerais state,
      Brazil) were analysed. The analytical methodology, which employed solid-phase
      extraction and high-performance liquid chromatography coupled to high resolution
      mass spectrometry (HPLC-MS/MS), was properly validated and resulted in limits of
      quantification (LOQ, S/N = 10) of 4.3 ng/L for diethylphtalate, 3.9 ng/L for
      nonylphenol, 3.6 ng/L for estradiol, 4.7 ng/L for ethynylestradiol and 2.5 ng/L
      for bisphenol. The five compounds were monitored for eight months, from sites
      where the hormones were occasionally found. Ethynylestradiol and estradiol
      concentrations varied from 5.6 to 63.8 ng/L. Bisphenol was present in all samples
      in a concentration that ranged from 8.6 to 168.3 ng/L. The other two compounds
      were at quantifiable levels in all collected samples, with nonylphenol varying
      from 25.9 to 1435.3 ng/L and diethylphthalate from 5.0 to 410.9 ng/L. The study
      showed that nonylphenol pollution seemed to originate from agricultural run-off,
      while diethylphthalate pollution originated from the discharge of domestic
      sewage. Risk analysis studies showed that the environmental concentrations of
      nonylphenol and dicthylphthalate do not present risks to human health; however,
      the concentrations found for bisphenol and ethinylestradiol could be toxic to
      humans, especially infants, if such compounds are not effectively removed at
      water treatment plants.

PMID- 21970184
TI  - Characteristics of phosphorus adsorption for a titanium mesostructure synthesized
      with various surfactants.
AB  - Eutrophication due to excessive phosphorus in water has been considered one of
      the most important environmental problems. In this study, a titanium
      mesostructure, prepared with different surfactant templates, was tested to
      confirm its applicability as an adsorbent for the removal of phosphorus and to
      evaluate the phosphorus removal efficiency. An X-ray diffraction analysis, the
      phosphorus adsorption isotherm and a kinetic test were performed on the titanium
      mesostructure synthesized with various molar ratios of base material to
      surfactant and different surfactant templates. It was revealed that the
      mesostructure synthesized with the molar ratio of 1.00/0.25 was the most
      uniformly and clearly formed and had the maximum adsorption capacity.

PMID- 21970185
TI  - Mel-18 controls the enrichment of tumor-initiating cells in SP fraction in mouse
      breast cancer.
AB  - Side population (SP) cell analysis has been used to identify and isolate a minor
      population of cells with stem cell properties in normal tissues and in many
      cancers including breast cancer cells. However, the molecular mechanisms that
      operate in tumor-initiating cells (TICs) in SP fraction remain unclear. The
      Polycomb group genes, including Bmi1 and Mel-18, have been implicated in the
      maintenance of hematopoietic stem cells (HSCs) and suggested to be oncogenic and
      tumor suppressive, respectively, in breast cancer. In this study, we determined
      the critical role of Mel-18 in the enrichment mechanisms of TICs with the SP
      phenotype in a mouse breast cancer cell line, MMK3, that was established from a
      breast cancer developed spontaneously in Mel-18+/- mice. The Mel-18 protein
      expression level significantly correlates to the percentage of SP fraction in the
      mouse breast cancer cell line MMK3 series. The comparison between MMK3V3 (V3)
      cells containing one copy of the Mel-18 gene and MMK3S2 (S2) cells having twice
      the amount of Mel-18 expression clearly demonstrates the above relationship.
      Similar results obtained with the percentage of ALDH+ cells in V3 and S2 further
      confirmed the correlation between protein expression level of Mel-18 and the
      TICs. More importantly, transplantation of SP and non-SP cells of V3 and S2 cells
      into the NOD/SCID mice clearly showed that the heterozygous level of Mel-18 leads
      to the disappearance of enrichment of TICs into SP fraction in vivo. Stem cell
      pathway focused gene expression profiling of V3 and S2 cells revealed that the
      genes Abcg2, Aldh1a1 and Dhh were highly down-regulated in V3 compared to S2.
      These results indicate that the precise Mel-18 expression level controls TIC
      enrichment mechanisms through the regulation of channel molecule of Abcg2 and
      functional TIC marker of Aldhlal. In conclusion, our findings revealed the
      significance of fine-tuning mechanisms for Mel-18 protein expression level in the
      maintenance of TIC into SP fractions in mouse breast cancer.

PMID- 21970186
TI  - Control of dry weight and tube feeding improved the general condition of a
      hemodialysis patient: report of a case.
AB  - Patients on long-term hemodialysis are at risk of developing malnutrition,and
      poor nutrient intake is an important factor in this. In the present case, we
      encountered a 55-year-old Japanese woman with end-stage renal failure and a past
      history of schizophrenia. Severe systemic edema was observed. Hemodialysis was
      started, but after one year she suddenly became unable to consume food orally,
      despite provision of a dietary plan by the nutrition support team (NST). Tube
      feeding was eventually implemented. Because the systemic edema did not improve,
      we decided to remove body fluid by intense hemodialysis. Hypotension was often
      observed during this hemodialysis, requiring dopamine. Over approximately 2
      months, the patient's dry weight fell from 73 kg to 62 kg, the patient's activity
      improved and she became able to eat orally again, allowing tube feeding to be
      stopped. Although the reason for the sudden anorexia has not been clarified, tube
      feeding and dry weight control was successful in the treatment of this
      malnourished hemodialysis patient.

PMID- 21970187
TI  - Norovirus gastroenteritis accompanied by marked elevation of transaminases.
AB  - A 56-year-old woman was admitted because of frequent watery diarrhea, vomiting,
      and abdominal cramps. An examination of the stool for norovirus antigen was
      positive, and a blood examination revealed a marked elevation of liver enzymes.
      Liver dysfunction, as well as symptoms related to gastroenteritis, was
      ameliorated solely by supportive treatment. Although liver injury concurrent with
      norovirus gastroenteritis is rarely documented and its pathogenesis remains
      unknown, clinicians should consider liver injury as one of the possible extra
      intestinal manifestations of norovirus gastroenteritis.

PMID- 21970188
TI  - Late recurrence of intractable epilepsy associated with MRI-occult pilocytic
      astrocytoma in the temporal lobe nine years after initial removal: a case report
      with surgical and late-seizure recurrence observations.
AB  - A 28-year-old male who presented a relapse of intractable epilepsy consisting of
      complex partial seizures with occasional secondary generalizations at the age of
      26, had undergone removal of a left mesial temporal lobe tumor at another
      hospital at 18 years old. Pathological examination at that time revealed a low
      grade astrocytoma, and the tumor was further treated by complementary adjuvant
      irradiation therapy. Magnetic resonance imaging (MRI) findings on admission
      portrayed a post-operative cavity anterior to the atrophied hippocampus on the
      left side with hyperintense in fluid-attenuated inversion recovery (FLAIR)
      images. There were no enhanced lesions in T1-weighted gadolinium images. As it
      was diagnosed as left mesial temporal lobe epilepsy with preoperative
      evaluations, the patient underwent left anterior temporal lobe resection (TLR).
      Intraoperative findings revealed that a small lump of grey tissue was attached to
      the anteromesial side of the sclerotic hippocampus. We surgically removed this
      and the tissue was a pilocytic astrocytoma. The patient has since remained
      seizure-free for 2.5 years. Seizure outcomes at postoperative 1-2 years are
      highly predictive of long-term outcomes after TLR for temporal lobe epilepsy
      (TLE). Late-seizure recurrence (> postoperative 2 years) with an initially
      successful outcome rarely occurs in TLR patients. This case report suggests that
      recurrence of even benign pilocytic astrocytomas may occur when seizure recurs in
      long-term follow-up.

PMID- 21970190
TI  - Budget impact analysis of pemetrexed introduction: case study from a teaching
      hospital perspective, Thailand.
AB  - OBJECTIVE: Thailand does not currently require Budget Impact Analysis (BIA)
      assessment. The present study aimed to estimate the annual drug cost and the
      incremental impact on the hospital pharmaceutical budget of the introduction of
      pemetrexed to a Thai teaching hospital. MATERIAL AND METHOD: The budget impact
      model was conducted in accordance with the Guidelines for preparing submissions
      to the Pharmaceutical Benefits Advisory Committee (PBAC). The model variables
      consisted of number of patients, growth rate of lung cancer, uptake rate of
      pemetrexed over time, unit prices of drugs, and the length and cost of treatment.
      Sensitivity analysis was performed to determine changes in budgetary impact due
      to variation of parameters or assumptions in the model. RESULTS: The introduction
      of pemetrexed was estimated to cause considerable costs for the teaching
      hospital. In the base-case analysis, the incremental costs were estimated at
      8,553,984 Baht in the first year increasing to 12, 118, 144 Baht, 17,820,800 Baht
      and 17,820,800 Baht in the following years. The 4-year net budgetary impact was
      20,154,480 Baht or approximately 127,560 Baht per patient. Sensitivity analyses
      found that number of treatment cycles andproportion of patients assumed to be
      treated with pemetrexed were the two most important influencing factors in the
      model. CONCLUSION: New costly innovative interventions should be evaluated using
      the BIA model to determine whether they are affordable. The Thai government
      should consider requiring the BIA study as one of the requirements for drug
      submission to assist in the determination of listing and subsidizing decision for
      medicines.

PMID- 21970189
TI  - Clinical responses to the combination of estradiol and drospirenone in
      symptomatic postmenopausal Thai women.
AB  - OBJECTIVES: To investigate the efficacy and tolerability of the oral hormone
      replacement therapy (HRT) containing 1 mg estradiol (E2) plus 2 mg drospirenone
      (DRSP) in Thai women with postmenopausal symptoms. MATERIAL AND METHOD: Fifty
      five Thai women with postmenopausal symptoms participated in this multicenter,
      open-label, non-comparative Phase IV study. The primary endpoint was the
      reduction of hot flushes after 12 weeks of treatment. Secondary endpoints
      included changes infrequency and intensity of menopausal symptoms as well as
      safety assessments after 4, 8, and 12 weeks of treatment. RESULTS: Treatment with
      1 mg E2 plus 2 mg DRSP reduced the frequency of hot flushes in 94.6% of women at
      the end of the 12-week treatment period. In 60% of women, the frequency of hot
      flushes was reduced to 10% or less, compared to baseline findings and 49.1% of
      women had no remaining hot flushes. Other postmenopausal symptoms such as vaginal
      dryness, urinary incontinence, dysuria, and dyspareunia improved The most common
      adverse events were vaginal bleeding or spotting and breast tenderness.
      CONCLUSION: The oral HRT of 1 mg E2 plus 2 mg DRSP was effective and well
      tolerated by Thai women suffering from postmenopausal symptoms.

PMID- 21970191
TI  - Impact of risk factors for recurrent ischemic stroke in Prasat Neurological
      Institute.
AB  - BACKGROUND: Recurrent strokes are more likely to be more disabling or fatal than
      first-even strokes. The high frequency of recurrences underscores the importance
      ofsecondary prevention. OBJECTIVE: Investigate risk factors of recurrent ischemic
      stroke and to compare the outcomes after treatment following the Thai stroke
      guideline between patients with recurrent ischemic stroke and patients without
      recurrent ischemic stroke. MATERIAL AND METHOD: Sixty-seven patients with
      recurrent ischemic stroke and 167 patients without recurrent ischemic stroke were
      included in the present study. All patients were evaluated for demographic data,
      modifiable risk factors, and treatment. RESULTS: Patients without recurrent
      ischemic stroke had better controlled level of systolic blood pressure, diastolic
      blood pressure, and higher high-density lipoprotein level than patients with
      recurrent ischemic stroke. Carotid stenosis was higher in patients with recurrent
      ischemic stroke (43.3% vs. 28.7%, p = 0.032). Patients with recurrent ischemic
      stroke received statin therapy (67.2% vs. 86.8%, p = 0.001) and folic acid (61.2%
      vs. 78.4%, p = 0.007) less than patients without recurrent ischemic stroke. The
      multivariate analysis showed that well controlled diastolic blood pressure (p =
      0.014), higher level of high-density lipoprotein (p = 0. 010), and receiving of
      statin (p = 0.002) were associated with decreased incidence of recurrent ischemic
      stroke. CONCLUSION: Well-controlled risk factors including blood pressure,
      fasting blood sugar, high-density lipoprotein, and low-density lipoprotein were
      crucial for the protection of recurrent ischemic stroke. Furthermore, the
      benefits of statin and folic acid therapies for the protection of recurrent
      ischemic stroke were emphasized

PMID- 21970192
TI  - Incidence and factors associated with overweight and obesity, and hypertensive
      disorder, among staff in a private healthcare setting: a retrospective cohort
      study.
AB  - OBJECTIVE: To determine the incidence and factors associated with overweight and
      obesity, and hypertensive disorder, among staff in a private healthcare setting.
      MATERIAL AND METHOD: The present retrospective cohort study examined the
      computerized data of Bumrungrad International (BI) Hospital staff that had
      undergone pre-employment and annual/bi-annual check-ups, between January 2000 and
      June 2006. RESULTS: Data for the 3,678 staff surveyed comprised 7,338 visits,
      with a median follow-up time of 1.9 years; 81.9% were females, and the mean age
      (SD) was 27.1 (6.8) years. On their first visit, 8.5% could be classified as
      overweight or obese (Body Mass Index-[BMI] of 25.0+ kg/m2). The overall incidence
      of these conditions was 22.2/1,000 person-years (95%; Confidence Interval [CI] =
      18.8-26.1). Cox's regression analysis revealed that incidence increased with age
      (Relative Hazard [RH] = 4.4 for age 20-44 years [95% -CI 1.6-12.2], and RH = 8.2
      [95% CI 2.4-27.5] for age > or = 45 years, reference: < 20 years), but decreased
      among the registered nurses and ancillary professional staff (RH = 0.3, 95% CI
      0.2-0.6). At cohort entry, 41.0% could be classified as pre-hypertensive (blood
      pressure 120-139/> 80-89 mmHg) and 1.9% as stages I and II hypertension. The
      overall incidence of hypertensive disorder was 16.9/1,000 person-years (95%; CI
      13.6-20.9). Baseline pre-hypertensive (RH 4.9, 95%; CI 2.6-9.3), males (RH 1.7,
      95%; CI 1.1-2. 7), age > or = 45 years (RH3.2, 95%; CI 1.0-10.5), and BMI (RH
      ranges 3.3-6 4) were identified as independent risk factors for incident
      hypertension. In addition, 2.5% were HBsAg-positive, and 33.3% had HBsAb antibody
      CONCLUSION: The present retrospective cohort study was instituted in a private
      healthcare setting, information generated resulted in changes to the health
      promotion programs of the organization.

PMID- 21970193
TI  - Normal data of left ventricular parameters in non-hypertensive patients using 320
      slice cardiac CT: a study on intra- and interobserver variability.
AB  - OBJECTIVE: Delineate normal data in a Thai population for global left ventricular
      function, left ventricular mass (LVM), and LV mass index (LVMI) by gated
      volumetric CT angiography (CTA). MATERIAL AND METHOD: Two hundred twenty seven
      patients with intermediate risk factors for CAD were referred for CT coronary
      angiography. The non-hypertensive and non-diabetic asymptomatic group was
      selected with negative coronary CTA. Pre-condition of mild stenosis or less than
      50% area stenosis was consistently met for inclusion in the present study. One
      hundred fifteen patients were included (31 males, 84 females, age range 38-76
      years, mean 54.6 +/- 7.2 for males and 54.0 +/- 6.8 for females respectively).
      RESULTS: Mean EDV, ESV, SV, CO, and EF in male and females were EDV 122.6 +/-
      17.3 vs. 94.9 +/- 16.6ml, ESV 48.2 +/- 9.9 vs. 34.1 +/- 9.1 ml, SV 74.5 +/- 14.2
      vs. 60.8 +/- 10.6 ml, CO 4.2 +/- 0.8vs. 3.6 +/- 0.7 Land EF 60.6 +/- 6.6 vs. 64.3
      +/- 5.6% respectively The mean LVM and LVMI were higher in males than females
      (LVM 134.6 +/- 21.4 vs. 96 9 +/- 20.3 g, and LVMI 76.8 +/- 12.4 vs. 61.1 +/-
      11.56 g/m2). Altman and Bland plot for each of them showed that the mean and
      standard deviation of the differences was constant throughout the range of
      measurements. Each histogram of differences showed that these differences
      correspond to approximately normal distribution, indicating that the required
      assumptions held for the use of 95% limits of agreement are valid. CONCLUSION:
      Data from this group represents healthy volunteers and this may serve as an
      important source of information representing normal reference values to be used
      for Thai patients.

PMID- 21970194
TI  - Outpatient drug oversupply at a teaching hospital in Thailand.
AB  - BACKGROUND: A part of rising drug expenditure in Thailand was causedfrom drug
      oversupply, which was a result from policy of civil servants to get direct
      reimbursement from Ministry ofFinance. OBJECTIVE: Describe the problem oforal
      drug oversupply at outpatient service in a teaching hospital and determine the
      cost that affects hospital between October 1, 2008 and September 30, 2009.
      MATERIAL AND METHOD: Data of oral drug prescribing for outpatients were
      retrievedfrom the hospital database in the format of Microsoft Visual Fox Pro 9.0
      and analyzed by Microsoft Access 2007. Two assessment methods are applied to
      estimate drug oversupply more than 30 days, by month and by year. In addition,
      September 2009 was selected to study for a pattern of monthly drug oversupply.
      RESULTS: Total oversupply expenditure for fiscal year 2009 was 56.9 million Baht
      when summedfrom monthly basis and 62.0 million when performed as a whole year.
      Oversupply expenditure was 2.12 to 2.73%per month in term of money and 2.91 to
      3.46% in term of quantity. In September 2009, cardiovascular & hematopoietic
      system had the most oversupply. By brand of drug, the most frequently oversupply
      were Calcium carbonate (7.60%), Simvastatin (3.69%) and Omeprazole (3.20%). In
      term of money, the top three highest costs were for Atorvastatin (7.27%),
      Clopidogrel (6.83%) and Rosuvastatin (4.24%). By health schemes, patients under
      CSMBS trend to be the most of prescribed drug oversupply at 8.31% (3.21 million
      Baht in September 2009) with average number of oversupply per patient at 1.83
      items and average day left per drug item at 61.83 days. CONCLUSION: The most
      oversupply expenditures were for chronic diseases. These data will focus the
      problem for hospital administrators to plan for suitable strategy to control drug
      oversupply in their hospital.

PMID- 21970195
TI  - Prevalence and some important risk factors of hypertension in Ban Paew District,
      second report.
AB  - BACKGROUND: Hypertension (HT) has been one of the leading global risk factors for
      health. Therefore, it is important to indicate groups ofpeople with high risk(s)
      of HT to provide them with lifestyles modification and checking blood pressure
      (BP) periodically for early detection of HT. OBJECTIVE: To determine the
      prevalence of HT and some important risk factors in suspected high-risk group.
      MATERIAL AND METHOD: Randomized villages in Ban Paew District, Samuthsakorn
      Province, Central Thailand, which were near the sea, were selected for this
      study. The authors conducted the survey between February and April 2002 and 2003,
      getting one volunteer from each house who was in the age of 40-69 years (y).
      Volunteers were advised to fast from 8 pm until next morning for blood drawn,
      checking the weight, height, and waist. BP was measured by using the automatic BP
      and history, physical examination, etc were done. BP at 140/90 mm Hg or higher
      either systole or diastole and persons with currently treatment would be
      diagnosed as hypertension. RESULTS: One thousand seventy nine volunteers with
      completed data were included. One hundred fifty three (14.2%) were known HT, 143
      (19.5%) out of 735 and 62 (32.5%) out of 191 volunteers, with no history of HT
      did not know that their BP reached hypertensive level. Therefore, 205 (22.1%)
      from 926 volunteers were hypertensive with 89 (26.6%) from 335 men, 116 (19.6%)
      from 591 women (p = 0.0145) and 32 (3.5%) with isolated systolic hypertension. HT
      increased significantly in age of 60-69 y, more than 50-59 y and 40-49 y, BMI
      over 25 (p = 0.0002) and drinking alcohol (p = 0.0384). However, it did not
      increase with smoking (p = 0.2139) and eating salty foods (p = 0.6568). The group
      which ate sour taste had borderline significance for negative risk of
      hypertension (p = 0.0489). CONCLUSION: The authors reported the prevalence of
      22.1% having hypertension in the age group of 40-69 years and up to 32.5% in the
      group of not knowing their BP. Hypertension significantly increased with older
      age group from 40-49 to 60-69y, male gender, BMI over 25, drinking alcohol.
      However, it didnot with borderline significance for being a negative risk of
      hypertension in eating sour taste group.

PMID- 21970196
TI  - Kidney stones recurrence and regrowth after extracorporeal shock wave lithotripsy
      and percutaneous nephrolithotomy.
AB  - OBJECTIVE: To estimate and compare the incidence rate of kidney stone recurrence
      and regrowth after ESWL with PCNL at one, two, and three years. MATERIAL AND
      METHOD: A retrospective cohort study was performed The study recruited patients
      aged more than 18 years, diagnosed with kidney stones and treated by ESWL or PCNL
      between January 2006 and August 2010 at the urological unit of a university
      hospital located in the northern part of Thailand. Data were retrieved from
      medical records and analyzed using exact probability test or student's t-test.
      Poisson regression was used to compare the recurrence rate and the regrowth rate
      between ESWL and PCNL. RESULTS: During three years of follow-up, the overall
      stones recurrence and regrowth were 15.5% and 25.1% in ESWL group and 12.6% and
      16% in PCNL group, repectively. At one, two and three years after treatment,
      stones recurrence rate in the ESWL group were 13.1, 7.5 and 7.3 per 1,000 patient
      months while in the PCNL group were 11.3, 6.1 and 5.4 per 1,000 patient-months.
      After ESWL stones regrowth rates were 29.1, 12.3 and 11.9 per 1,000 patient
      months, whereas after PCNL were 11.3, 6.9 and 6.9 per 1,000 patient-months,
      respectively. In comparison to PCNL, the relative recurrence rate after ESWL
      presented as incidence rate ratio (IRR) were 1.1 (95% CI; 0.4-3.2, p = 0.762),
      1.2 (95% CI; 0.6-2.6, p = 0.517) and 1.4 (95% CI; 0.8-2.5, p = 0.271) at 1, 2 and
      3 years, respectively. For regrowth, the IRRs were 2.6 (95% CI; 1.1-6.5, p =
      0.012), 1.8 (95% CI; 0.9-3.4, p = 0.048), and 1.7 (95%CI; 1.1-2.9, p = 0.017) at
      1, 2 and 3 years, respectively. CONCLUSION: Patients after ESWL had a higher
      trend ofrecurrent rates and statistically significant higher regrowth rates, in
      comparison with those after PCNL.

PMID- 21970197
TI  - Clinical study of a new design multifunction dynamic external fixator system for
      open tibial fracture.
AB  - BACKGROUND: The tibial shaft is one of the most common sites of open fracture.
      External fixators emerged as the treatment of choice for high energy open tibial
      fractures because they were easy to apply, allow sufficient access for wound care
      and provide sufficient mechanical fixation for patient mobilization and bone
      healing. Based on the advantages of dynamization in increased union rate and the
      simplicity of monolateral frame, a new design dynamic external fixator system was
      developed for definite treatment in open tibial fracture. OBJECTIVE: To evaluate
      the clinical results of open tibial fractures treated with a new design dynamic
      external fixator system until healing. MATERIAL AND METHOD: The case series of 60
      patients with open tibial fracture treated with the new design dynamic external
      fixator system for acute and definitive-treatment frame between 2005 and 2009.
      According to the system of Gustilo and Anderson, 14 fractures were classified as
      type II, 43 as type IIIA, and three as type IIIB. Partial weight bearing with
      crutches was instructed when tolerable for dynamization. When there were
      evidences of fracture healing in both clinical and radiographic, external fixator
      was removed. RESULTS: All fractures united. The median union time was 12 weeks
      (range, 10-15) in type 11, 16 weeks (range, 10-24) in type IIIA, and 20 weeks
      (range, 20-21) in type IIIB. Iliac bone grafting was performed in six cases at a
      mean time of 3.8 weeks to enhance bone union. Seven cases (12%) developed
      pintract infections. No deep infection was found in the present study. Ninety
      five percent of fractures united with less than 10 degrees angulation in any
      plane. No instrument failure was found. The external fixator frame could be
      reused. CONCLUSION: The new design dynamic external fixator system successfully
      treated open tibial fractures with a good result and low complication rate. It is
      simple, safe, and easy to use.

PMID- 21970198
TI  - Prospective non-randomized comparative clinical outcome of computer assisted
      total knee arthroplasty with and without a minimally invasive approach.
AB  - OBJECTIVE: Compare clinical outcomes of computer assisted total knee arthroplasty
      using the LCS knee implant with (CAMITKA) and without (CATKA) minimally invasive
      surgery. MATERIAL AND METHOD: The author prospectively performed 71 computer
      assisted total knee arthroplasties (TKA) in group of the present study using the
      Ci navigation system in a non-randomized manner. RESULTS: CAMITKA subjects had a
      mean operation time of 105 minutes, average incision length of 9.1 cm, mean total
      blood loss of 541 ml, mean time to ambulation of 25.4 hours, and required
      approximately 10 and 18 days using walkers and canes respectively, before
      ambulating unaided CATKA subjects had a mean operation time of 81 minutes,
      average incision length of 13.5 cm, mean total blood loss of 599 ml, mean time to
      ambulation of 45.4 hours, and required 17 and 27.5 days using walkers and canes
      respectively, before ambulating unaided. All outcome differences have statistical
      significances, except blood loss. Mechanical axis alignment measured from post
      operative radiographic assessment showed that 2.5% of all knees were outliers and
      average axis deviations were 1.39 degrees and 1.34 degrees for CAMITKA and CATKA
      subjects, respectively. No complications were detected. CAMITKA is advantageous
      with respect to recovery time. CONCLUSION: Minor surgical pitfalls were
      experienced with CAMITKA regarding visualization and initial registration of the
      navigation system. However, they may be corrected by coupling navigation with CT
      scan, fluoroscopy, and/or ultrasound Additionally, accurate mechanical axis
      alignment shows that computer assisted surgery technology allows minimal invasive
      surgery in TKA because it allows visualization of areas not directly revealed
      without aid.

PMID- 21970199
TI  - Two-year outcome of hydroxyapatite mixed with autogenous bone marrow and local
      bone graft for posterolateral lumbar fusion.
AB  - OBJECTIVE: To determine the outcome of hydroxyapatite (HA) mixed with autogenous
      bone marrow (BM) and local bone graft in posterolateral lumbar fusion. MATERIAL
      AND METHOD: Twenty-three patients who had posterolateral fusion with posterior
      instrument using HA mixed with BM and local bone graft between December 2003 and
      August 2005 were prospective analyzed. Degree of pain using visual analog scale
      (VAS) was evaluated at preoperative and 2, 4, 6, 9, 12, and 24 postoperative
      months. Radiographs were assessed for spinal fusion at 4, 6, 9, 12, and 24
      postoperative months. RESULTS: The improvement of pain was demonstrated in all
      patients postoperatively. Radiographic outcomes revealed solid and doubtful
      fusion in one of 23 patients (4.3%) and 13 of 23 patients (56.5%) at six months
      respectively. After two-year follow-up, one patient had solid fusion while 22
      patients (95.6%) had doubtful fusion. CONCLUSION: Despite the posterolateral
      lumbar fusion using HA mixed with BM and local bone graft provided good clinical
      results, the radiographic results of spinal fusion were questionable in most
      cases.

PMID- 21970201
TI  - Parenting: what are the critical attributes?
AB  - OBJECTIVE: Identifying the critical attributes of the parenting concept. MATERIAL
      AND METHOD: The parenting attributes are the process, activity, and interaction
      regarding to rearing and educating a child, which is undertaken by parent or
      parental figure. Those aim at developing a child's growth, development, and well
      being. CONCLUSION: The specific parenting attributes can be applied to practice,
      education, and research in the area of pediatric, family and community health
      care.

PMID- 21970200
TI  - Dual dietary intake problems among under-five years old children living in an
      armed conflict area of southern Thailand.
AB  - This survey examined nutritional intake and the effects of armed conflict on
      energy-protein inadequacy amonng children aged one to less than five years. Fifty
      health centers were randomly selected. Three children were randomly selected from
      each 12-month old interval age groups in each health center. Four hundred seventy
      eight children and their primary caregivers were recruited. Food intake was
      collected from a single 24-hour food recall and was computed to percentage of the
      Thai Dietary Reference Intake (DRI). Violent event rates were classified by
      quartiles. Dietary intake stratified by age groups was examined. Logistic
      regression was used to examine association between armed conflict and inadequacy
      of food intake. Average of DRI was above 100% for both energy and protein intake.
      Snacks contributed to one-fourth of energy intake. Inadequacy of energy and
      protein intake was 27% and 7%, respectively. There was no association between
      armed conflict and inadequacy of energy and protein consumption.

PMID- 21970202
TI  - Clinical profiles of Thai patients with ocular myasthenia gravis in Siriraj
      Hospital.
AB  - Ninety-six patients with ocular myasthenia gravis (OMG) seen at Siriraj Hospital
      during 1994 to 2004 were retrospectively reviewed. There were 59 female (61.5%)
      and 37 (38.5%) male patients with mean ages of 39.5 and 33.8 years, respectively
      Patients presented with initial symptoms of only ptosis in 46.9%, only diplopia
      in 13.5% and both ptosis and diplopia in 39.6%. However, diplopia alone is
      uncommon in childhood OMG. Fifteen percent developed systemic symptoms within two
      years of diagnosis. Thyroid function test was abnormal in 27.5% of investigated
      patients. Most abnormalities were hyperthyroidism. Thymoma associated with OMG is
      a rare condition. Most purely OMG patients can control the disease by
      pyridostigmine, prednisolone or immunosuppressive drugs.

PMID- 21970203
TI  - The prevalence and pattern of pneumatization of Onodi cell in Thai patients.
AB  - BACKGROUND: The Onodi cell (sphenoethmoidal cell) is an anatomical variation of
      the most posterior ethmoid air cell the pneumatizes laterally and/or superiorly
      to the sphenoid sinus and is intimately in contact with the optic nerve. If it is
      infected or goes unrecognized during surgery it may result in serious damage to
      the optic nerve. Nowadays, computed tomographic scans of paranasal sinuses (CT
      PNS) have been used to detect variations in paranasal sinus anatomy However there
      is a lack of data about the variations of Onodi cell. OBJECTIVE: To determine the
      prevalence and various patterns of Onodi cell. MATERIAL AND METHOD: Axial,
      coronal, sagittal and sagittal oblique (parallel to the optic canal) CT scans of
      the paranasal sinuses, nasopharynx, neck and orbit performed at Srinagarind
      Hospital between January 1, 2004 and November 30, 2006 were reviewed A pilot
      study was carried out to investigate the inter-rater reliability of the
      identification of Onodi cell between the radiologist and rhinologist until the
      kappa value was 0.74. During the main study, the radiologist and rhinologist
      interpreted the CT scans independently. If there was a discordant opinion
      concerning the presence of Onodi cell, a consensus was reached by discussion
      between the rhinologist and the radiologist. RESULTS: 187 CT scans (374 sides)
      were included Sagittal oblique view detected Onodi cell in 185 sides 49.5% (95%
      CI: 44.4-54.5). The patterns of Onodi cell were classified into three patterns.
      In the first pattern, the Onodi cell extended only superiorly to sphenoid sinus
      (46%; 95% CI: 38.9-53.1). In the second pattern, it extended only laterally to
      sphenoid sinus (1%; 95% CI: 0.3-3.9). The last pattern was a combined type,
      lateral and superior to sphenoid sinus (53%; 95% CI: 45.8-60.0). CONCLUSION: The
      prevalence of Onodi cell diagnosed by CT scans was 49.5% (95% CI 44.4-54.5) and
      the most common pattern was the combined type. This information may be useful for
      those who perform endoscopic sinus surgery.

PMID- 21970204
TI  - Dynamic contrasted MR imaging in differentiation of recurrent malignant soft
      tissue tumor from posttreatment changes.
AB  - OBJECTIVE: To investigate dynamic contrast enhanced magnetic resonance imaging
      (DCE-MRI) in term of differentiation recurrent malignant soft tissue tumor (MSTT)
      from post-treatment changes. MATERIAL AND METHOD: DCE-MRI was performed in
      consecutive patients in two-year periods to differentiate recurrent MSTT from
      post-treatment (surgery radiotherapy chemotherapy) changes. The steepest slope
      (SS) ratio between the artery and the lesion, sensitivity, and specificity were
      calculated. RESULTS: Thirty-five DCE-MRI studies were performed in 30 patients,
      which included 14 males and 16 females with an age range from 12 to 71 years
      (median 45.81 year). Thirteen were with recurrence and 22 were with post
      treatment changes. The SS ratios were ranged from 0.66 to 29.15. The lesions with
      the SS ratio > 9.28 were all benign at follow up of at least two months, whereas
      those with SS ratio < 1.05 were all recurrent tumors proven by biopsy or surgery.
      Overlapping occurred when the SS ratios > 1.05 but < 9.28 in which the recurrence
      was 42.31%. The chance of having recurrence rather than post-treatment changes
      was approximately two andfive times in patients with the ratio of 5. 07 and 1.55,
      with the specificity of 54.55% and 90.91%, respectively CONCLUSION: The SS ratio
      between the artery and the lesion has limitations to differentiate recurrent MSTT
      from posttreatment changes. It is useful when the ratio is less than 1.05
      (malignant) or more than 9.28 (benign). The chance of having recurrence rather
      than post-treatment changes was approximately two and five times in patients with
      the ratio of 5.07 and 1.55, respectively The less value the ratio is, the more
      possibility to be recurrent tumor.

PMID- 21970205
TI  - Plasticity of the motor cortex in patients with brain tumors and arteriovenous
      malformations: a functional MR study.
AB  - OBJECTIVE: Test the hypothesis about the potential role of functional MRI (fMRI)
      to evaluate the plasticity of the cortical motor areas in patients with brains
      tumors and brain arteriovenous malformations (AVMs) and measurement of the lesion
      to-fMRI activation distance for predicting risk of new motor deficit after
      surgery. MATERIAL AND METHOD: This was a retrospective study. The present study
      population enrolled eight patients with motor cortex lesions. Cortical motor
      representations were mapped in these patients harboring tumor or AVMs occupying
      the region of primary motor cortex (M1). Five patients had known diagnosis of
      primary brain tumor including glioblastoma multiforme, (n = 1), diffuse
      astrocytoma (n = 2), dysembryoplastic neuroepithelial tumor (DNET) (n = 1) and
      unknown pathology (n = 1). Three patients had known diagnosis of brain AVMs.
      Three patients showed hemiparesis at the time of presentation. Focal/generalized
      seizure or headache was present in the remaining patients. Simple movements of
      both hands were performed Localization of the activation in the affected
      hemisphere was compared with that in the unaffected hemisphere and evaluated with
      respect to the normal M1 somatotopic organization. Distance between the location
      of the fMRI activation (M1) and margin of the lesion was recorded. RESULTS:
      Cortical activation was found in two patterns: 1) functional displacement within
      affected M1 independent of the structural distortion induced by the tumor or AVMs
      (n = 7) and 2) presence of activation within the non-primary motor cortex without
      activation in the affected or unaffected M1 (n = 1). CONCLUSION: Brain tumor or
      AVMs led to reorganization within the somatotopic affected M1 and can expand into
      non-primary motor cortex area. Distortion of the anatomy alone by the space
      taking lesion did not influence the location of the reorganized cortex. No
      particular type of reorganization pattern could be predicted fMRI could be
      localized reorganized cortex and was found to be a useful tool to assess the
      lesion-to-activation distance for predicting risk of new motor deficit after
      surgery. The present study thus emphasizes the importance of considering
      additional fMRI with structural MRI to evaluate individual differences in
      cortical plasticity for treatment planning, particularly in the neurosurgical
      procedure.

PMID- 21970206
TI  - Symptom checklist-90 (SCL-90) in a Thai sample.
AB  - BACKGROUND: Symptom Checklist-90 (SCL-90) has been used on both normal and
      clinical samples in Thailand over a long period. However, its validity and
      reliability have not yet been systemically reported OBJECTIVE: Survey the
      validity and reliability of SCL-90 in a more extensive way, using a normal sample
      of people throughout Thailand, and investigate the psychometric properties of the
      Thai version of SCL-90. MATERIAL AND METHOD: Four hundred forty eight subjects
      participated in the present study of which 50.4% were male and with ages ranging
      from eighteen to 90 years, by providing demographic data and completing the Thai
      version of SCL-90 and the 16-Personality Factor (16-PF) Questionnaire. The
      demographic data was analyzed using descriptive statistics, and Cronbach's alpha
      was used to determine its internal consistency Factor and confirmatory factor
      analysis were performed to construct the validity, and convergent and
      discriminant validities were calculated to generate Pearson's correlation
      coefficients using the 16-PF subscales. RESULTS: The mean of the global symptoms
      index was found to be 0.70 +/- 0.46, with the means of the symptoms ranging from
      0.53 for Psychoticism to 0.98 for Obsessive-compulsive disorder. We found to be a
      significant difference in sub-scales across genders, age groups, geographic
      regions, educational levels, occupations, and incomes, but the symptom dimension
      patterns revealed were similar to those of previous studies. Depression and
      anxiety were the key components to show variance between the normal and clinical
      samples. The measurements demonstrated good internal consistency with Cronbach's
      alpha, at 0.97, but did not yield relevant correlations between some of the 16-PF
      sub-scales, as was expected. Moreover, factor analysis revealed that SCL-90 has a
      uni-dimensional construct. CONCLUSION: The Thai version of SCL-90 showed a good
      internal consistency, but poor discriminant validity with most items occurring
      for the depression, anxiety and interpersonal sensitivity dimensions. It is
      recommended that some of the items be revised for clinical studies.

PMID- 21970207
TI  - Amyloidosis and respiratory tract involvement: report of two cases.
AB  - Amyloidosis is a group of diseases in which amyloid deposit in the extracellular
      space in an abnormal insoluble fibrillar form. The most important amyloid
      precursors are immunoglobulin light chain (AL) and serum amyloid-associated
      protein (AA). Amyloidosis can manifest as localized or systemic disease and
      respiratory system is one of the target organs that can be involved by amyloid.
      The authors report two cases of pulmonary amyloidosis presented with diffuse
      interstitial pulmonary amyloidosis and tracheobronchial involvement.

PMID- 21970208
TI  - A recalcitrant acrodermatitis continua of Hallopeau successfully treated with
      etanercept.
AB  - Acrodermatitis continua of Hallopeau (ACH) is considered as a localized form of
      pustularpsoriasis that is usually refractory to the treatment. The condition is
      characterized by sterile pustules, onychodystrophy, anonychia, and osteolysis of
      distal phalanges. The authors report a case of recalcitrant ACH who previously
      failed to topical corticosteroid, methotrexate, acitretin, and phototherapy and
      rapidly responded to etanercept in combination with acitretin. The primary
      varicella infection occurred during the therapy. The patient was able to
      discontinue etanercept within four months after starting the treatment. The
      lesion was then under-controlled by acitretin and topical clobetasol ointment
      with an 8-month clinical remission.

PMID- 21970209
TI  - Health sector: the challenges.

PMID- 21970210
TI  - The burden and management of infants with life-long and irreversible hearing
      impairment in Nigeria.
AB  - If left untreated or treated late and inappropriately, sensorineural hearing
      impairment has several adverse, irreversible and life-long health, psycho-social
      and economic consequences for the affected infants and their families. This
      seminar paper sets out to describe the burden, current practices and management
      options for sensorineural or permanent hearing impairment in early infancy for
      primary care physicians in Nigeria against the backdrop of their role as primary
      or first contact for all health consultations. Available studies suggest that up
      to 2.7% or 162,000 of the 6 million infants born annually may have permanent
      hearing impairment. The underlying aetiological factors may not be determined in
      the majority of the infants thus limiting the effectiveness of any primary
      prevention initiatives. However, the affected infants can be detected accurately
      with objective screening technologies such as otoacoustic emissions and auditory
      brainstem response in hospital or community settings. The ethical and scientific
      rationale for this intervention has been well established. Barring the challenge
      of parental follow-up default which is not insurmountable, affected infants and
      their families can be supported to establish appropriate auditory-based
      communication, avoid potentially harmful traditional therapies and child neglect
      commonly associated with childhood hearing impairment. Primary care providers in
      private and public practice have a crucial role in guiding parents to seek timely
      and appropriate services from ear care providers and child development
      specialists to ensure optimal child growth and developmental outcomes. On-going
      parental commitment to and active participation in the selected intervention
      programmes are essential to satisfactory long-term outcomes.

PMID- 21970211
TI  - Study of serological and clinical factors among juvenile rheumatoid arthritis
      cases admitted to Mofid Children's Hospital and Imam Hossein Hospital, Tehran,
      Iran.
AB  - INTRODUCTION AND AIM: Juvenile Rheumatoid Arthritis is the most common
      rheumatologic disease of childhood period. The aim of study was to compare ANA
      positive and ANA negative cases. PATIENTS AND METHODS: This observation study was
      performed as correlation research. All cases with diagnosis ofJRA who visited
      Mofid Children's Hospital and Imam Hossein Hospital were included in this study.
      Duration of this study was from 2006, 1 October till 2008, 31 October. All
      patients were examined carefully by an experienced pediatric rheumatologist. Age,
      sex, disease onset, age at diagnosis, RF, ANA, HLA-B27, ESR, type of disease,
      disease activity, and duration of inactivity were included in this study. ANA
      titer was measured by immunoflurocence technique. Patients were categorized
      according to sex, ANA, and type of disease and then group was compared with each
      other. Data was analyzed by SPSS Ver. 16 (Chicago, IL, USA). This study was
      approved by Ethical Committee of university. RESULTS: In this study, 61 cases
      were enrolled. Twenty five cases (41%) were males and 36 cases were females. Mean
      of age at disease onset was 6.1 +/- 3.1 (Range 6 months to 12.5 years). Mean of
      age at disease diagnosis was 6.7 +/- 3.2. Mean of age at time of study was 7.6 +/
      3.5 (1.4 to 14 years). From all cases, 38 cases were oligoarticular, 18 cases
      were polyarticular and 5 cases were systemic onset. From 61 cases, 22 (36.1%)
      cases, had ANA positive JRA. Of these cases, 14 cases were oligoarticular and 8
      cases were polyarticular. CONCLUSION: Except for sex and morning stiffness, there
      is significant correlation between type of disease and ANA,RF,HLA-B27, response
      to treatment, early onset erosion, subcutaneous nodule, and uveitis (P < 0.05).
      There is significant correlation between sex and ANA, RF, HLA-B27, early erosion,
      response to treatment, subcutaneous treatment, and uveitis (P < 0.05). There is
      significant correlation between ANA seropositivity and HLA-B27, early erosion,
      response to treatment, uveitis and subcutaneous nodule. Our results showed that
      there is significant correlation among ANA and other factors except morning
      stiffness. Another prospective study is recommended.

PMID- 21970212
TI  - Diagnostic approach of childhood pulmonary tuberculosis in endemic areas of
      Southeast Nigeria.
AB  - There is the need to ascertain the diagnostic approach on which medical doctors
      based their diagnosis of childhood pulmonary tuberculosis especially in
      tuberculosis endemic areas. AIM OF THE STUDY: To determine the diagnostic
      approach used by medical doctors in the diagnosis of childhood pulmonary
      tuberculosis. METHODOLOGY: A cross sectional study, using structured
      questionnaires to collect data from medical doctors whose daily routine include
      seeing sick children was carried out. RESULTS: The common diagnostic approach or
      criteria were ranked by medical doctors in descending order of importance as
      follows; clinical features elicited from patients' history was ranked-1 by 56.4%
      (or 23 of 218); bacteriological investigation to isolate Mycobacterium
      Tuberculosis was ranked-2 by 22.5% or 49 of 218; radiological investigation to
      demonstrate typical changes consistent with active pulmonary tuberculosis was
      ranked-3 by 25.2% or 55 of 218; therapeutic trial with standard anti tuberculosis
      drugs was ranked-4 by 52.3% or 114 of 218; immunological investigation using
      tuberculin skin testing was ranked-5 by 30.3% or 66 of 218; and residual ranking
      of histological investigation using tissue biopsy was ranked-6 by 15.6% or 34 of
      218. Therapeutic trial with standard anti tuberculosis drugs was consistently
      ranked as 4th by most groups of clinicians. CONCLUSIONS: Most clinicians from
      different subgroups studied followed a fairly similar order in the diagnosis of
      childhood pulmonary tuberculosis with a high premium placed on clinical features,
      bacteriologic, radiologic and therapeutic trial with anti tuberculosis drugs. The
      specialist in paediatric medicine relied more on clinical features and
      therapeutic trials for their diagnosis of childhood pulmonary tuberculosis.

PMID- 21970213
TI  - Combined transfacial and transcranial approach for tumours of the nose and
      paranasal sinuses with intracranial extension.
AB  - OBJECTIVES: To describe the importance of craniofacial approach in extensive
      tumours of the nose and paranasal sinuses with intracranial extension. MATERIALS
      AND METHODS: This is a retrospective study and descriptive analysis of
      craniofacial approaches to extensive tumors of the nose and paranasal sinuses
      that were carried at Usmanu Danfodiyo university teaching Hospital Sokoto Nigeria
      over a nine year period (July 1999 to June 2008). RESULTS: Out of 111 patients
      seen with tumours of the nose and paranasal sinuses during the period, 29(26.1%)
      were radiologically reported through computerised tomographic scan to have
      intracranial extension. Twenty-four (82.8%) were males while 5 (17.2%) were
      females. Twenty five (86.2%) patients underwent transfacial approach ( modified
      lateral rhinotomy). Intraoperative findings in these cases only warranted the
      repair of dural tear in 6 cases through the transfacial approach who had anterior
      skull base invovlement while 4 had combined transcranial and transfacial
      approaches (anterior craniofacial resection). Therefore only 10 (34.5%) patients
      of all the radiologically reported cases of intracranial extension were confirmed
      intraoperatively to have intracranial extension (5 males, 5 females) with an age
      range of 1 1/2 to 60 years and mean age of 34.1 years. One patient had orbital
      exenteration also carried out. Four out of 10 patients are alive after a minimum
      period of 2 years follow up due to extensive intracranial spread and late
      presentation of the patient. CONCLUSION: Extensive tumours of the nose and
      paranasal sinuses with suspected intracranial extension requires not only
      computerized tomographic scans to assess the extent of the tumour but also a
      combined transfacial and transcranial approach to successfully resect the tumour.

PMID- 21970214
TI  - Pathology of deaths from carbon monoxide poisoning in Port Harcourt: an autopsy
      study of 75 cases.
AB  - BACKGROUND: Carbon monoxide (CO) poisoning is a notable cause of death at homes
      and industries that is posing public health problem worldwide that requires an
      elaborate study. OBJECTIVE: To study and characterize deaths resulting from the
      noxious gas (CO). DESIGN: A ten year (January 1st, 1995 December 31st 2004)
      autopsy study. SETTING: Port Harcourt, Nigeria. METHODOLOGY: Coroners and
      hospital autopsies performed by the authors at the University of Port Harcourt
      Teaching Hospital (UPTH), other hospitals and private mortuaries in Port Harcourt
      on deaths from carbon monoxide poisoning were studied over ten years. The
      circumstances of death reported by police were accidental, homicidal or suicidal;
      and other autopsy findings were used for the study. RESULTS: A total of seventy
      five autopsies were studied; out which 21 (28.0%) were females and 54 (72.0%)
      males giving a ratio 1:2.6 male dominance. The highest frequency of death 25
      (33.3%) occurred in the age group 60 69 years; while the least 3 (4%) occurred in
      the age group 0 9 years. The youngest was an unborn 7 month old male fetus while
      the eldest was 85 years old female. The most common was accidental carbon
      monoxide poisoning which accounted for 48 (64%) cases. While Homicidal CO
      poisoning .was 24 (32%) and suicidal CO poisoning was 3 (4.0%). Body recovered
      from fumy electric generator rooms was 46 (61.3%) while least frequency was
      bodies recovered from naked flame 3 (4%). CONCLUSION: Carbon monoxide poisoning
      is posing a serious public health problem when ever it occurs. There is need for
      public enlightenment about this gas as it is related to fumes from generator, car
      exhausts, poorly ventilated rooms and enclosed chambers in order to reduce the
      carnage associated with it both at home and industries.

PMID- 21970215
TI  - Quality of teaching provided by surgical residents: an evaluation of the
      perception of medical students.
AB  - BACKGROUND: Surgical residents teach and interact with Medical students during
      surgery clerkship. However, the quality of teaching by surgical resident as
      perceived by medical students has not been assessed in our setting. The aim of
      this report is to evaluate the quality of teaching provided by surgical residents
      as perceived by Medical students METHODS: This is a cross sectional study
      involving final year 2005-2006 medical students ofAhmadu Bello University Zaria,
      Nigeria. The characteristics and skills of surgical residents' teaching role as
      perceived by medical students were determined. The Information was obtained using
      a structured questionnaire. Data obtained was analyzed using SPSS version 11.0
      RESULTS: A total of 120 medical students participated in the study. The age range
      was 24-36 years (mean 26.88 + 2.19). There were 87 (72.5%) males and 33 (27.5%)
      females. In assessing the qualities of a teacher among surgical residents, 83
      (69%) of the students believed the surgical resident has good teaching skills,
      101 (84%) believed they were committed to teaching, 118 (98%) they were
      available, 109 (91%) had inspirational ability. In assessing the qualities of a
      surgeon, 116 (97%) believed the surgical resident has enthusiasm for surgery, 106
      (88%) empathy for patients, 78 (65%) fund for knowledge. Assessment of the
      qualities of a supervisor revealed 118 (98%) Got medical students involved, hands
      on, 78 (65%) set fair expectations, 113 (94%) Gave them feedbacks, 118 (98%)
      supervised them adequately. In term of the qualities of the person 107 (89%)
      believed a surgical resident is supportive, 94 (78%) considerate, 115 (96%)
      friendly, 108 (90%) fun to work with. Overall assessment perceived by medical
      students revealed Senior Registrar having better qualities of teaching than
      Registrar. These qualities were rated good and outstanding by majority of the
      medical students. CONCLUSION: Medical students' perception of teaching provided
      by surgical residents is encouraging in our setting. This emphasizes the
      important role of the surgical resident in undergraduate medical training. Thus,
      the teaching skills of surgical residents should be encouraged and sustained.

PMID- 21970216
TI  - Grandmultiparity: outcome of delivery in a tertiary hospital in southern Nigeria.
AB  - BACKGROUND: Grandmultiparity is traditionally associated with increased risk of
      complications during pregnancy and delivery. Reports from developed countries
      where obstetric facilities are excellent and the standard ofperinatal care is
      high indicate that currently, obstetric complications among grandmultipara are
      now independently associated with progressive maternal age. In Nigeria and other
      developing nations however, grandmultiparity still contributes a significant
      proportion of the obstetric population. The aim of this study is to evaluate the
      outcome of delivery of grandmultiparous patients at the University of Uyo
      Teaching Hospital. METHODS: The case records of all grandmultiparous patients who
      delivered at the University of Uyo Teaching Hospital, Uyo over a six-year period
      were studied. RESULTS: Grandmultiparous women constituted 6.4% of the parturients
      who delivered in the hospital during the study period. Their ages ranged from 20
      45 years with majority (71.5%) being 30-39 years. Majority (77.9%) were para 5
      and 6 and 326 (80.1%) of the patients booked and received antenatal care in the
      hospital. Majority of the booked patients (79.8%) initiated antenatal care after
      32 weeks of gestation while all the unbooked patients 68 (16.7%) and the
      antenatal clinic defaulters 8 (2.0%) were brought from unorthodox health
      facilities when they developed obstetric complications. Two hundred and forty
      three patients (59.7%) had spontaneous vaginal delivery, 15 (3.7%) of the
      patients had laparotomy for ruptured uterus and out of these ten of them (66.7%)
      had a subtotal abdominal hysterectomy while five (33.4%) had uterine repair and
      bilateral tubal ligation. The perinatal mortality rate was 128/1000 births. There
      were three maternal deaths, two from eclampsia while one followed postpartum
      haemorrhage resulting in a maternal mortality rate of 7.4/1000. CONCLUSION: The
      prevalence of grandmultiparity in our centre is relatively low. It is, however,
      associated with high perinatal and maternal morbidity and mortality. We advocate
      widespread community enlightenment on the importance of limitation of family size
      and number of child births. There is need for community based studies in our
      environment accessing the knowledge and attitude of women with high parity
      towards contraception.

PMID- 21970217
TI  - Factors associated with decreased survival from neonatal malaria infection in
      Jos, North Central Nigeria.
AB  - BACKGROUND: Malaria is a serious cause of morbidity and mortality in the neonatal
      period and account for a significant number of fetal wastage. Its diagnosis is
      difficult because of the overlap in clinical presentation with other infectious
      disease in the neonatal period. This study set out to examine the factors that
      are associated with an increased risk of mortality in neonates admitted with
      malaria. METHOD: Forty one neonates presenting between January and June 2009 were
      enrolled after obtaining ethical approval and informed consent from the mothers.
      Information collected include gestational age, age at presentation, birth weight,
      clinical symptoms, associated medical conditions and pertinent pregnancy history.
      RESULTS: Of the 41 neonates studied, 24 (58.5%) were females, 29 (70.5%) were
      term neonates and 12 (29.3%) had low birth weight. Overall mortality was 24.4%,
      more male neonates (70%) had malaria compared to females (50.0%) and neonatal
      malaria was associated with a longer hospital stay (p < 0.001). Female neonates
      (RR = 0.81, CI = 0.69 0.95), neonatal malaria (RR = 0.63, CI = 0.54 0.73) and
      maternal negative HIV status (RR = 0.22, CI = 0.15 0.32) was associated with
      lower risk of mortality. Whereas, multiple symptoms at presentation (RR = 1.67,
      CI = 1.42 1.96), multiple medical conditions (RR = 1.59, CI = 1.37 1.84) and
      maternal malaria in pregnancy (RR = 1.54, CI = 1.23 1.29) were associated with
      increased risk of mortality. Maternal IPT use, gestational age and birth weight
      did not have any statistically significant relationship with mortality.
      CONCLUSION: Neonatal malaria is a significant cause of neonatal mortality; the
      risk of which is higher with the presence of other co-morbid factors. We suggest
      a review of the IPT program and the introduction of maternal malaria screening at
      time of delivery.

PMID- 21970218
TI  - Domestic violence in pregnancy among antenatal attendees at the University of
      Port Harcourt Teaching Hospital, Port Harcourt.
AB  - BACKGROUND: Domestic violence is common worldwide. When it occurs in pregnancy it
      is associated with maternal and perinatal morbidity and mortality. It is a human
      rights violation with medical implication which is under-diagnosed and under
      reported. This study sought to determine the prevalence of domestic violence
      during pregnancy and the factors that promotes domestic violence at the family
      unit. METHODOLOGY: A cross sectional study of antenatal clients seen at the
      antenatal booking clinic of the University of Port Harcourt Teaching Hospital
      from 1st June to 31st December 2007. Five hundred clients selected from a simple
      random technique completed an interviewer administered structured questionnaire
      which sought information on domestic violence. Data collected was entered into a
      spreadsheet and analyzed using the statistical package SPSS 15.00 for Windows.
      RESULTS: The prevalence of domestic violence during pregnancy in this group was
      7.8%. Those who experienced domestic violence were mainly those with low
      education and low parity. The commonest form of domestic violence was verbal
      abuse (shouting, cursing) occurring in 43.5% of those who have been abused in the
      index pregnancy and 1.2% of the victims of domestic violence suffered physical
      injuries from domestic violence in previous pregnancies. However, less than one
      third disclosed the incident. Women whose husbands indulge in substance abuse or
      are without jobs were more likely to experience domestic violence. Abdominal pain
      and miscarriage were the commonest obstetric complications following domestic
      violence-in pregnancy in this group. CONCLUSION: Eight percent of our antenatal
      mothers suffer domestic violence and many of them are unlikely to report it.
      Unemployment and substance abuse in the partners are major associated factors.
      Domestic violence in pregnancy has far-reaching adverse consequence on the mother
      and her unborn fetus such as miscarriage especially when it occasions bodily
      harm.

PMID- 21970219
TI  - Contraceptive choices and practices among urban women in southeastern Nigeria.
AB  - BACKGROUND: Determining the contraceptive choices among the women is the first
      step in scaling up family planning methods. OBJECTIVE: To determine the
      contraceptive choices and practices as well as the underlining factors among
      market women in Nnewi, southeastern Nigeria. SUBJECTS/METHOD: This is a cross
      sectional descriptive study of market women, that assessed their contraceptive
      choices and practices. RESULT: Knowledge about family planning was 96.5%. One
      hundred and seventy five (44.0%) of the interviewed women were currently using a
      family planning method while 59.0% had ever used a method. The common methods in
      use were the natural method (24.1%), withdrawal method (7.5%) and the IUCDs
      (6.1%). The commonest ever used method was the natural method (26.7%) followed by
      withdrawal method (10.6%) and condom (7.8%). Fear of family planning commodities
      interfering with future fertility was the commonest reason for non use of family
      planning services (14.6), followed by the fear of the side effects (10.6%).
      Seventy one (17.8%) of the non-users had no reason. The use of family planning
      services was significantly high among the women aged 35 and above (x2 = 9.98; P =
      0.04) and the (x2 = 23.8; P = 0.00). Focus group discussions indicated that
      husband's refusal, fear of side effects, cancer and delayed fertility were the
      main barriers to the use of family planning methods. CONCLUSION: The
      contraceptive prevalence rate among Nnewi market women is high and cuts across
      all religions and social classes. However, the methods in common use are
      associated with high failure rates. The use of the more reliable methods should
      be encouraged.

PMID- 21970220
TI  - The clinical and pathological features of hepatocellular carcinoma in Nnewi,
      Nigeria.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) remains the commonest malignancy of
      the liver. In spite of the recent advances in treatment, prognosis is still
      abysmal especially in developing countries. This article aims to review the
      clinical and pathological features of HCC in a tertiary hospital at Nnewi.
      METHOD: This was a cross-sectional study. Patients with HCC seen at the Medical
      Out-patient Department or admitted into the Medical wards of the Nnamdi Azikiwe
      University Teaching Hospital Nnewi were recruited. The study lasted from June
      2007 to May, 2008. Subjects were clinically evaluated and blood samples collected
      for HBsAg, anti-HCV and HBeAg assays. RESULTS: The prevalence of HCC was 2.4%. Of
      the 60 patients studied, 38 were males and 22 were females with a male to female
      ratio of 2:1. Their ages ranged from 19-86 years with a mean age of 50.62 +/-
      17.54. The mean duration of symptoms before presentation was 16 weeks and the
      mean duration from onset of symptoms to death is 20 weeks. Common presenting
      symptoms were painful right hypochondrial mass, abdominal swelling, weight loss,
      early satiety and fatigue while coagulopathy, ascites and hepatic encephalopathy
      were the most common complications. Multiple lesions affecting both lobes of the
      liver was seen in 48 patients on ultrasound, 36.6% were positive for HBsAg of
      which 41% were HBeAg positive. HCV antibodies were present in 8.3% of the
      patients. Well differentiated HCC of the pseudo-glandular variety was the most
      common histological type. CONCLUSION: HCC affects middle aged Nigerians. Though
      well differentiated, it presents late with clinical features of advanced disease
      leading to death within six months. It is more often associated with chronic HBV
      than HCV infection.

PMID- 21970221
TI  - Cryptosporidiosis among HIV-infected persons in the Niger Delta of Nigeria.
AB  - BACKGROUND: Since the discovery of acquired immunodeficiency syndrome (AIDS),
      many studies demonstrated that intestinal parasites were frequently associated
      with pictures of severe diarrhoea in patients with HIV. OBJECTIVES: To determine
      the prevalence of Cryptosporidiosis among HIV-infected persons in the Niger Delta
      of Nigeria. METHOD: Faecal samples from One hundred and five HIV/AIDS infected
      subjects made up of 48 males and 57 females aged 18-54 years, mean age and CD4
      count of 36.14 +/- 8.46 years and 320 +/- 140 cells/microl respectively were
      evaluated for Cryptosporidiosis using the Modified Ziehl-Neelsen staining method.
      RESULTS: Of the one hundred and five faecal samples examined, 3 (2.9%) were
      positive for cryptosporidium oocyst. Prevalence was significantly higher among
      females 2/57 (3.5%) compared to males 1/48 (2.1%), among subjects with diarrhoea
      3(11.5%) and among subjects with CD4 lymphocyte count < 200 cells/microl (p <
      0.01). CD4 count of subjects positive for cryptosporidium oocyst was
      significantly lower (150 +/- 50 cells/microl). The mean CD4 count of subjects
      with diarrhoea was significantly lower (mean 180 cells/microl) compared to those
      without diarrhoea (360 cells/microl). CONCLUSION: Our study indicates that the
      prevalence of intestinal colonization due to Cryptosporidium is significantly
      higher among HIV-infected persons presenting with diarrhoea and low CD4
      lymphocyte count of < 200cells/microl and re-emphasizes the need to incorporate
      routine faecal parasitological examination (FPE) in the follow up management of
      patients with HIV/AIDS. This is likely to optimise treatments in these patients
      by eradicating opportunistic pathogens and improve the quality of life of these
      patients.

PMID- 21970222
TI  - Audit of cardiothoracic diseases seen at the National Cardiothoracic Centre Enugu
      Nigeria.
AB  - BACKGROUND: The University of Nigeria Teaching Hospital, Enugu was designated the
      national centre of Excellence for Cardiothoracic diseases, because of the
      availability of skilled manpower. This study was therefore undertaken to see the
      pattern of cardiothoracic diseases managed in the surgical unit of the centre and
      to see if the objectives of its establishment are being achieved. METHOD: A
      retrospective analysis of in-patient admission records managed surgically or
      conservatively between 2000 and 2004 was made. RESULTS: A total of 704 cases were
      identified; 469 (55.6%) men, 121 (17.2%) women and 114 (16.2%) children.
      Majority, 163 (23.25%) were between the age range of 20-29 years. Enugu, the
      State where the hospital is domicile had the highest admission rate of 318
      patients (45.15%) while the 19 Northern States had a total of 67 patients
      (9.51%). Chest wall disorder constituted the majority of cases (28.69%) of which
      chest trauma from road traffic accident was the majority 49.6%. Most patients
      were hospitalised for an average of 2-4 weeks (56%). CONCLUSION: The study
      revealed a low admission rate with a declining trend over the years and a skewed
      distribution of their origin. It also identifies militating factors and draws the
      attention of the relevant authorities to take necessary actions to stem this
      trend.

PMID- 21970223
TI  - Gross vulva odema complicating severe pre-eclampsia/eclampsia: a case series.
AB  - BACKGROUND: Pre-eclampsia/Eclampsia is one of the leading causes of maternal and
      perinatal morbidity and mortality in sub-Saharan Africa including Nigeria. Pre
      eclampsia presenting with gross vulva edema is not commonly encountered and its
      significance is yet to be established. METHODOLOGY: A clinical case series of
      four patients with Pre-eclampsia that presented with gross vulva edema. RESULT:
      Three patients had evidence of worsening severity of disease characterized by
      acute renal failure with oliguria, HELLP Syndrome, Intrauterine Growth
      Restriction and adverse perinatal outcome. The fourth was complicated with
      eclampsia, adult respiratory distress and maternal death. CONCLUSION: The
      presence of gross vulva oedema in pre-eclampsia may be an indicator of severity
      of disease and or deteriorating fetomaternal condition. Further studies are
      required to demonstrate the significance of gross vulva edema in pre-eclampsia.

PMID- 21970224
TI  - Chronic thromboembolic pulmonary hypertension with pulmonary infarction occuring
      in a hypertensive.
AB  - We present a 72-year-old man and a known hypertensive with poor drug compliance
      seen here on 22-03-06, with a 4-year history of progressive dyspnoea, associated
      with cough and a wheeze. On examination he was chronically ill looking with
      altered state of consciousness, pale, centrally cyanosed, febrile (T-38 degrees
      C), in respiratory distress (RR-33 pm). Significant chest radiological findings
      include marked aortic unfolding and cardiomegaly, with biventricular involvement.
      Numerous nodular opacities in both lung fields especially the Right side with
      right apical opacification/thickening. Treatment as appropriate was instituted
      but unfortunately the patient succumbed after thirty days on admission and an
      autopsy carried out revealed multiple pulmonary infarcts with pulmonary thrombo
      embolism.

PMID- 21970225
TI  - Speech and language difficulties in a patient with schizophrenia-like disorder: a
      case report.
AB  - Neurocognitive complications, such as speech and language dysfunctions are common
      comorbids in psychiatric patients with underlying medical conditions, such as
      stroke. Ascertaining a diagnosis is not usually easy, especially in the hands of
      the primary physicians who first attend to such patients. In addition, making
      diagnosis purely on previous psychiatric presentations, without thorough
      neurological and neurocognitive evaluation, is a mistake psychiatrists should
      avoid. Cultural belief systems in Nigeria play important role in the choice of
      care people with psychiatric problems receive, and the dearth in the country's
      mental health personals is a be-deviling handicap to providers of mental health
      services in the country. The author presents the case of a 52 year old man with
      schizophrenia-like psychosis that was complicated by speech and language problems
      following a cerebrovascular accident. In conclusion, doctors especially
      psychiatrists should be alert to co morbid physical illnesses in patients with
      psychiatric presentations.

PMID- 21970226
TI  - Health as a national agenda.

PMID- 21970227
TI  - Endometriosis.
AB  - BACKGROUND: Endometriosis is a common mysterious and fascinating gynaecological
      condition with diverse clinical manifestations, highly variable and unpredictable
      clinical course with decreased quality of life. Despite extensive research,
      endometriosis is fraught with controversies. METHODS: Review of pertinent
      literature on endometriosis, selected references, internet services through
      gynaecological search which have been critical in the understanding of this
      puzzling gynaecologic condition were included in the review. RESULTS:
      Endometriosis most commonly afflict women in there late 20s and 30s. The classic
      symptom complex include dysmenorrhoea, dyspareunia, menorrhagia and infertility.
      About 30% of the patients are asymptomatic. The incidence of infertility amongst
      women suffering from endometriosis ranges from 30%-40%. The factors implicated in
      causing endometriosis-associated infertility are multiple and its management is
      shrouded in controversy, complex and imperfectly understood. CONCLUSION: Inspite
      of diverse clinical manifestations, variable and unpredictable clinical course,
      there is a chance to improve pregnancy rates with improvement in assisted
      reproductive technology.

PMID- 21970228
TI  - Tuberculosis: a review of current concepts and control programme in Nigeria.
AB  - BACKGROUND: The burden of tuberculosis in Nigeria is the highest in Africa.
      Therefore, improved knowledge of health workers on the current issues concerning
      the disease, including the National guideline, is important for effective disease
      control. METHODS: An in-depth search of relevant literature on the subject area.
      This includes texts and operational documents of the Nigerian national
      tuberculosis programme, as well as online searches using Pubmed, Africanjournal
      online (Ajol), and Google scholar. RESULTS: About one third of the world
      population is infected with tuberculous bacilli with up to 10% lifetime risk of
      developing the disease. Pulmonary tuberculosis (PTB) especially the reactivated
      latent infection is the major source of the infection in communities. In an
      effort to increase case detection, a single acid fast bacillus in at least one of
      two sputum smears is currently adequate to diagnose PTB. Furthermore, there is a
      global effort to eliminate the disease by the year 2050 and these efforts are
      coordinated in Nigeria by the National tuberculosis controlprogramme. CONCLUSION:
      Tuberculosis is an impediment to human development in developing countries,
      especially in this era of HIV pandemic. Continuing education of health
      professional on tuberculosis and its accessible treatment, will improve patients'
      education, proper management and appropriate referral.

PMID- 21970229
TI  - Evaluation of the level of awareness of the role of folic acid in the prevention
      of neural tube defects amongst women of reproductive age in a tertiary health
      institution.
AB  - BACKGROUND: Neural tube defects are major cause of infant mortality and
      disability. Their occurrence has been linked to folate deficiency during
      pregnancy. Periconceptional use of folate has been shown to significantly reduce
      their incidence. Awareness of this relationship is key to adopting appropriate
      measures to prevent them. This study was carried out to assess the level of this
      awareness among reproductive-age female employees in a tertiary hospital.
      METHODOLOGY: Questionnaires designed to assess respondents' knowledge about
      neural tube defects and folic acid were completed by women of child-bearing age
      working in various departments of the University of Port Harcourt Teaching
      Hospital. Data were collated and analysed by a third party who had no knowledge
      of the respondents. RESULTS: 94.4% of the respondents had some knowledge about
      folic acid. 29.6% knew something about neural tube defects. 24.1% were aware that
      folate has a beneficial role in their prevention. 70.4% said they would not take
      it daily if they were not pregnant. CONCLUSION: The level of awareness about the
      role of folate in prevention of neural tube defects among respondents in this
      study is low; and thus there is poor response to suggestions regarding its
      periconceptional use. There is need to enhance this awareness to ensure that
      populations at risk benefit from research on the subject.

PMID- 21970230
TI  - Seroprevalence of hepatitis B surface antigen among patients attending Aminu Kano
      Teaching Hospital, Kano.
AB  - OBJECTIVE: To study the seroprevalence of Hepatitis B viral (HBV), infection
      among patients attending Aminu Kano Teaching Hospital in Kano metropolis.
      PATIENTS AND METHOD: This is a retrospective study in which patients tested for
      hepatitis B virus using hepatitis B surface antigen (HBsAg) as a marker were
      reviewed over 3 years. A total of 6,395 patients comprising of 4,040 males and
      2,355 females including adults and children were tested for HBsAg from January
      2004 to December 2006. Over this period, 1509 sera were tested in 2004, 2,322 in
      2005 and 2,564 in 2006. RESULTS: Among the 6,395 patients, 703 (11.4%) comprising
      of 240 (10.2%) females and 490 (12.1%) males were positive for HBsAg. The highest
      prevalence was seen at the extremes of life in which 19.4% and 16.9% were seen
      among patients below 10 years and above 50 years respectively. The yearly trend
      of HBV surface antigenemia was 220 (14.6%) in 2004, 235 (10.1%) in 2005 and 275
      (10.7%) in 2006. CONCLUSION: We conclude that the prevalence of HBsAg among
      patients attending Aminu Kano Teaching Hospital, Kano is high and highest
      prevalence is seen at the extremes of life.

PMID- 21970231
TI  - Combined transfacial and transcranial approach for tumours of the nose and
      paranasal sinuses with intracranial extension.
AB  - OBJECTIVES: To describe the importance of craniofacial approach in extensive
      tumours of the nose and paranasal sinuses with intracranial extension. MATERIALS
      AND METHODS: This is a retrospective study and descriptive analysis of
      craniofacial approaches to extensive tumors of the nose and paranasal sinuses
      that were carried at Usmanu Danfodiyo University Teaching Hospital, Sokoto
      Nigeria over a nine year period (July 1999 to June 2008). RESULTS: Out of 111
      patients seen with tumours of the nose and paranasal sinuses during the period,
      29(26.1%) were radiologically reported through computerised tomographic scan to
      have intracranial extension. Twenty-four (82.8%) were males while 5 (17.2%) were
      females. Twenty-five (86.2%) patients underwent transfacial approach (modified
      lateral rhinotomy). Intraoperative findings in these cases only warranted the
      repair of dural tear in 6 cases through the transfacial approach who had anterior
      skull base invovlement while 4 had combined transcranial and transfacial
      approaches (anterior craniofacial resection). Therefore only 10 (34.5%) patients
      of all the radiologically reported cases of intracranial extension were confirmed
      intraoperatively to have intracranial extension (5 males, 5 females) with an age
      range of 1 1/2 to 60 years and mean age of 34.1 years. One patient had orbital
      exenteration also carried out. Four out of 10 patients are alive after a minimum
      period of 2 years follow up due to extensive intracranial spread and late
      presentation of the patient. CONCLUSION: Extensive tumours of the nose and
      paranasal sinuses with suspected intracranial extension requires not only
      computerized tomographic scans to assess the extent of the tumour but also a
      combined transfacial and transcranial approach to successfully resect the tumour.

PMID- 21970232
TI  - Anaesthetic requirement in spinal cord injured patients undergoing operation
      below the level of cord injury.
AB  - BACKGROUND: Anaesthesia in spinal cord injured (SCI) can be hazardous. In
      complete injuries above T6, the abnormal state of the respiratory and the
      cardiovascular systems pose special problems. The objective of this study
      therefore was to evaluate the anaesthetic requirements in patients with complete
      SCI undergoing operation below the level of the cord lesion. PATIENTS AND METHOD:
      The medical records and the operation notes of all patients with complete SCI who
      underwent surgical operations between January 2001 and December 2005 were
      reviewed. Information about their demographics, level of injury, indications for
      operation, type of operation done and the type anaesthesia used were collated.
      The choice anaesthesia was guarded by the proximity of operation site to the
      level of cord transaction and by patient's preference. The pre-operative and
      intra-operative blood pressure, pulse rate and respiratory rate were used to
      monitor cardiovascular and respiratory responses. RESULTS: They were twenty
      eight, all male except one. The age range was 13-67 years with an average of32
      years. The level of cord lesion varied. The thoracic spine was most involved
      followed by the cervical spine. The most common indication for operation was
      pressure sore. The anesthetic requirement varied, and ranged from general
      anesthesia (GA) to no anaesthesia at all. Three broad groups were observed: no
      anaesthesia; sedation with diazepam; and general anaesthesia. There was no
      remarkable change in the blood pressure readings in the three groups. However,
      three patients who had GA and whose operation sites were in the twilight zone had
      remarkable changes in the pulse and respiratory rates. CONCLUSION: Even though
      spinal patients are insensate below the level of their injury, significant
      proportions that need operation below the level of cord lesion require
      anaesthesia.

PMID- 21970234
TI  - Knowledge, attitudes and practice of confidentiality of patients' health records
      among health care professionals at Federal Medical Centre, Bida.
AB  - BACKGROUND: The quality of information shared with health care professionals
      depends on their ability to keep it confidential especially in this information
      technology age when unguided access is imminent. In view ofthis, the study
      described knowledge, attitude and practice of confidentiality of patients' health
      records amongst health care professionals at Federal Medical Centre Bida,
      Nigeria. METHODS: A semi-structured self-administered.questionnaire on the
      subject was administered to 313 health professionals chosen by stratified random
      sampling in the hospital. RESULTS: Majority (161, 66.8%) of the participants were
      less than ten years in practice. Virtually, all (232, 96.3%) have heard about
      confidentiality mostly from schools (134, 55.6%), on-the-job (61, 25.3%) and from
      multiple sources (18, 7.5%). On responsibility for confidentiality; only 35
      (14.5%) knew it is the responsibility of every health professional, while the
      majority; 117 (48.5%) felt it was exclusively meant for health information
      management professionals. Responses to issues on confidentiality range from 58.1%
      (revelation of documented next of kin to relatives of dead patients by staff) to
      94.2% (employing the service of untrained interpreter). Very few (28, 11.6%)
      argued that confidentiality and privacy are not synonymous. Recommendations given
      to improve the practice of confidentiality include among others, observance of
      good health records practice by all professionals/stakeholders, continuing
      sensitisation of all staffandsanction against erring staff. CONCLUSIONS:
      Although, most professionals were aware of confidentiality, there appears a gap
      of in-depth knowledge and lack of awareness of respective responsibility towards
      it. However, they will do better if given the enabling environment and continuing
      education on the subject.

PMID- 21970233
TI  - Trends of myomectomy at the University of Nigeria Teaching Hospital (UNTH) Enugu
      Nigeria.
AB  - BACKGROUND: Uterine fibroid is the commonest female genital tumour occurring
      within the reproductive age group, and abdominal myomectomy is the most offered
      surgical treatment in our environment. There is need to audit this practice in
      our centre so as to observe the practice pattern and outcome of myomectomies in
      Enugu, Nigeria. OBJECTIVE: To audit myomectomies, the practice pattern and
      outcome at the University of Nigeria Teaching Hospital Enugu-Nigeria. METHODS: A
      5-year retrospective study of myomectomies performed in UNTH Enugu between
      January 1, 2004 and December 31, 2008. Data relating to socio-demographic
      characteristics, indication for surgery, intraoperative haemostatic measures,
      estimated blood loss, use of drain, duration of hospital stay and complications
      were abstracted and analyzed. RESULT: A total of 122 abdominal myomectomies were
      performed and 70.5% of the patients were aged 30-39 years and 80% were nullipara.
      Lower abdominal swelling and discomfort were the commonest presentation and
      indication for the surgery. Tourniquet was used for haemostasis in 57.4% while
      postoperative drain was inserted in 52.6%. 24.6% received blood transfusion and
      the average duration of hospital stay was 8.6 days. Complications were mild, with
      pyrexia as the commonest complication (28.7%). There was no mortality.
      CONCLUSION: Though myomectomy is safe and tolerated in our centre, a consensus
      practice pattern through a prospective study is required to further improve
      outcome.

PMID- 21970235
TI  - The delusion of halitosis: experience at an eastern Nigerian tertiary hospital.
AB  - BACKGROUND: Halitosis is a recognized problem in dental practice. Some
      individuals have the belief that they have offensive mouth odour which neither
      the dental clinician nor any other person can perceive. This condition is known
      as delusional halitosis. Delusional halitosis can be classified as either Pseudo
      halitosis or Halitophobia depending on the response to initial treatment.
      Halitophobia is an olfactory reference syndrome and is a psychological condition
      that the dental surgeon is ill equipped to treat alone. This study aimed to
      analyse patients diagnosed with delusional halitosis, highlight our experiences
      and make suggestions for improved management of such patients. METHODOLOGY: All
      patients who presented at the dental clinics of University of Nigeria Teaching
      Hospital between January 2005 and December 2009 with a primary complaint of oral
      malodour were examined organoleptically. Those with obvious halitosis and known
      psychological conditions were excluded from the study Once a diagnosis of
      delusional halitosis was made, each patient was educated on the nature of
      halitosis, its causes and prevention. They then received oral prophylaxis and
      oral hygiene instructions. They were then recalled at one week, four week and six
      week intervals to establish a definitive classification. RESULT: 18 out of the 25
      patients who presented were diagnosed with delusional halitosis. 61% of them male
      and 39% of them female with an average age of 30yrs. Pseudo halitosis comprised a
      majority of the cases seen (13). Halitophobia was seen in the minority (5).
      Reasons sited for believing that they had mouth odour by the patients studied
      included, peoples reaction when they were in close proximity and how people
      tended to avoid them (94.4%), ability to self perceive the foul odour from their
      mouths (55%) and 27.8 % said they had been told by another person that they had
      bad breath. All the patients had very good oral hygiene, with a tendency to over
      indulge on oral care products and tended to use mouthwash, breath mints and
      sweets in an attempt to mask the perceived odour with a few having excessive
      tooth brushing habits. Most had visited 2 or more other physicians within the
      year of presentation at the clinic with the same complaint. The patients were
      embarrassed (55.6%) frustrated (27.6%), self conscious (11.1%) or felt helpless
      (5.6%) by their perceived foul mouth odour, but none claimed to have suicidal
      thoughts. CONCLUSION: In all cases of delusional halitosis, there is usually an
      underlying psychosomatic problem, which can range from an over valued belief to a
      frank delusional disorder where the individual can hardly be dissuaded from their
      belief of mouth odour. A multidisciplinary approach to treatment between the
      dental surgeons and the psychological specialists may present the best approach
      for the patients.

PMID- 21970236
TI  - Pathology of deaths from mob action in the Niger Delta Region of Nigeria. A study
      of 38 consecutive autopsies.
AB  - BACKGROUND: Mob action is posing an undue social and public health problems in
      Niger Delta region of Nigeria; as victims who were said to have committed crime
      were violently killed without fair trial by law. There is need to research into
      the pattern, cause and frequency of deaths from mob action. AIM: To study the
      pattern cause and frequency of death from mob action. SETTING: Niger Delta Region
      of Nigeria. DESIGN: Aten (1999-2008) consecutive autopsy on victims ofmob action.
      METHODOLOGY: A thorough autopsy was performed on all the victims following
      standard method after being severed with the coroner's inquest form by police.
      Variables considered were the ages and sex, yearly frequency, methods applied in
      the killing and reasons that motivated the killing. These were obtained from the
      coroner's inquest forms, police, relations and eye witnesses. RESULT: A total of
      thirty eight bodies were examined. Thirty four (89.5%) were males and four
      (10.5%) females; giving a male to female ratio of 8.5:1. The youngest was 16
      years old male while the oldest 72-year-old male. Majority 30 (78.9%) of deaths
      occurred below the age of 50 years. Youths of the age group 20 29 were most
      involved and the highest frequency 12 (21.1%) of death was recorded in 2004.
      Beating 14 (36.8%) was the most common method applied for the killing while
      political violence 15 (39.5%) was the most common circumstances for the killing.
      CONCLUSION: Killing by mob action is a social, legal and public health problem in
      the Niger Delta region of Nigeria that requires a swift government intervention
      to reduce the carnage associated with it. Problems of economic inequality, youth
      unemployment and corruption should be adequately addressed by the Nigerian
      government.

PMID- 21970237
TI  - Maxillofacial injuries in Calabar south-south, Nigeria: a 5 year study of jawbone
      fractures.
AB  - OBJECTIVES: The aim of this study is to highlight the overall uniqueness of the
      pattern of presentation of maxillofacial injuries seen at the Department of Oral
      and Maxillofacial Surgery of the University of Calabar Teaching Hospital, Calabar
      south-south Nigeria between January 2000 and December 2004 and to share our
      experience in terms of occurrence, seasonal fluctuations and the adequacy of
      treatment methods in our environment. MATERIALS AND METHODS: Case notes of all.
      the 200 maxillofacial trauma patients were retrieved, examined and analyzed with
      regards to age, gender and cause of injury, socio-demographic data, diagnosis,
      pattern of presentation, distribution and treatment. RESULTS: A male-to-female
      ratio of 3.65:1 was obtained. Out of the 200 patients the highest incidence of
      injury was in the 20-30 year age group 85 (n=85; 42.5%). The major causes of
      injuries were motorcycle (n=74; 37%), vehicle (n=62; 31.5%) and assault (n=40;
      20%). Six (3%) river-related or boat accidents were recorded. Industrial and
      sports related accidents contributed the least (n=5; 2.5%). CONCLUSION: Road
      traffic accident had the highest proportion of the entire maxillofacial injuries
      with more males affected than females. Seasonal distribution showed a bimodal
      peak variation of May-June and September-January. This paper calls for the
      reinforcement of measures for the prevention of automobile accident and the
      establishment of more maxillofacial specialist centers with modern equipment for
      effective management of maxillofacial injuries.

PMID- 21970238
TI  - The Rivers State, Nigeria Eye Care Program--the first few steps towards achieving
      V2020.
AB  - AIM: To outline the outcome of the first eye camp of the eye care program in
      Rivers state which was established only in 2008 to reduce the burden of blindness
      in the state as revealed by the Nigerian national blindness and visual impairment
      survey results released in 2008 as much as possible to the lowest before the year
      2020. METHODOLOGY: A descriptive analysis of the activities of the Prevention of
      blindness committee, Rivers established in 2008 by the Ministry of health, Rivers
      state, Nigeria. An analysis of the first eye camp held at the Rumuigbo health
      center, Rumuigbo, Port Harcourt is also presented from the records made at the
      time of the camp. The activities were partly sponsored by the Ministry of Health,
      Rivers state. Data analysis was with the help of a statistician using SPSS
      version 11. RESULTS: The recently released Nigerian National Survey on Blindness
      and Visual Impairment revealed that about 15,000 people are blind from cataract
      in Rivers state, Nigeria. Over a 3 day period to mark World Sight Day 2010, a
      total of 455 persons were screened for cataract surgery at the above venue. The
      mean age was 46.2 years (SD+/- 17.55) with an age range of 1 and half to 99
      years. The male female ratio was 1:1. A total of 125 patients (27.5%) had
      cataract of which 83 were mature. Refractive error also affected 125 people
      (27.5%). Sixty-five people (14.3%) were suspected to have glaucoma while 13(2.9%)
      and 45 people (9.9%) presented with corneal opacities and allergic
      conjunctivitides respectively. Other conditions seen include conjunctival
      degenerations, inflammatory conditions, staphylomata etc. Cataract surgery was
      performed on 51 people (40.8% of those with all diagnosed with cataract and 61.4%
      of those with mature cataract. Other conditions that could not be treated on
      location were referred to the teaching hospital and the state hospital nearby.
      The postoperative cases were also referred to the same hospitals for followup.
      Follow up showed that majority (n=38, 74.5%) attained 6/24 to 6/60 VA range by
      the end of the first week with improvement to the 6/12 to 6/18 range by the end
      of the first month in 30 (58.8%) of the patients. CONCLUSION: It is highly
      desirable for periodic eye camps to take place in Rivers state as it was an eye
      opener that even within the township, most people who are avoidably blind are
      within easy reach of secondary and tertiary health facilities that can offer eye
      care. Satisfactory visual outcome was obtained in the majority of cases operated
      upon. Government is within their rights to fund subsequent programs adequately as
      their input is necessary for sustainability. This will help reduce the burden of
      the cataract blind in the state though it is not likely that V2020 will be
      achieved at the current rate.

PMID- 21970239
TI  - Haemogram pattern at diagnosis of malignant disorders and variations post
      chemotherapy.
AB  - A total of eighty patients with various malignancies seen between September 2008
      and April 2009 at the University of Nigeria Teaching Hospital, (UNTH) Ituku
      Ozalla Enugu Nigeria had their haemogram values done at Days 0 and 12 of the
      first cycle of their various chemotherapeutic regimens. They were adult patients
      who had been diagnosed of various malignancies, consisting of Breast cancer 36
      patients (45%), Non-Hodgkin's iymphoma 8 (10%), Hodgkin's lymphoma 13 (16.25%),
      Colorectal carcinoma 6 (7.5%), Multiple myeloma 7 (8.75%), Cervical carcinoma 1
      (1.25%) and other malignancies 9 (11.25%). Haematological indices evaluated
      include: packed cell volume, haemoglobin concentration; total white blood cell
      count, platelet count and erythrocyte sedimentation rate. The socio demographic
      data of the patients were assessed from a questionnaire. There were 27 males
      (33.75%) and 53 females (66.25%). The age of the patients ranged from 18-80 years
      with a median of 45 years. Haematological parameters which were found to be
      significantly reduced include: haemoglobin concentration, packed cell volume and
      total white cell count.

PMID- 21970240
TI  - Perception and care-seekling behaviour for post partum morbidity among mothers in
      Enugu south east, Nigeria.
AB  - BACKGROUND: Postpartum Care is necessary to monitor and ensure return to normal
      of some physiological changes that occurred during pregnancy and delivery, and
      any abnormalities detected should be treated. The aim of this study is to
      describe the perception of and care seeking behaviour for maternal morbidity
      following childbirth among mothers in Enugu, Nigeria and determine if they depend
      on the socio-demographic characteristics ofmothers. METHODS: A cross-sectional
      survey of women who had recent deliveries was done. Quantitative and qualitative
      methods of data collection were used. Data analysis was by descriptive and
      inferential statistics at 95% level of confidence and manual content analysis.
      RESULTS: Three hundred and seventy-one respondents who had, at least, one self
      reported morbidity following childbirth were studied. Only approximately 43.1%
      perceived their symptoms as abnormal and 39.5% sought medical attention for their
      symptoms. Inaccurate perception was influenced by the severity of symptoms as
      well as cultural beliefs on what constitutes abnormal symptoms following
      childbirth. Correct perception of morbidity was dependent on maternal age (p =
      0.002) and educational status (p = 0.004) whereas positive care seeking behaviour
      was dependent on area of residence (p = 0.03). A greater proportion of mothers
      aged 30 years or below had accurate perception compared to older mothers (p =
      0.02). A greater proportion of rural dwellers sought medical attention for their
      symptoms compared to urban dwellers. CONCLUSION: Inaccurate perception of, and
      poor care seeking behaviour for postpartum morbidity were common among a sample
      of women with recent deliveries in Enugu due largely to cultural beliefs about
      morbidity following childbirth. Correct perception and positive care seeking
      behaviour were not enhanced by older age, greater educational attainment of
      mothers or residence in urban areas.

PMID- 21970241
TI  - Pattern of gynaecological cancers in University of Nigeria Teaching Hospital,
      Enugu, south eastern Nigeria.
AB  - BACKGROUND: Gynaecological cancers are among the leading causes of cancer related
      deaths worldwide. The objective of this study was to determine the pattern and
      relative frequencies of gynecological cancers as seen at the University of
      Nigeria Teaching Hospital (UNTH), Ituku/Ozalla, Enugu, Southeastern Nigeria.
      METHODS: An analysis of retrospective clinical data from the ward admissions and
      discharge books and the operating theatre record books. RESULTS: During the 10
      year period under study (2000-2009), 407 cases of gynaecological cancers were
      admitted into the hospital. The age range of these women was 21-80years with mean
      age of 54.6 +/- 14.2 years. The commonest gynaecological cancers in women less
      than 30 years of age were choriocarcinoma (36.1%) and ovarian cancer (33.3%).
      After 30 years, cervical cancer became the commonest cancer. Overall, cervical
      cancer was by far the commonest gynecological cancer constituting 78% of all the
      cases, followed by ovarian cancer (8.9%), choriocarcinoma (4.3%), endometrial
      cancer (4.1%), vulva cancer (4.0%) and leiomyosarcoma (0.5%). There was no case
      of vaginal cancer during the study period. Anaemia was the commonest sequelae,
      complicating 55% of the cases, followed by genital fistulae (12%), infertility
      (3%), renal failure (3%), and pulmonary complications (2%). CONCLUSION: Cervical
      cancer is by far the commonest gynaecological cancer in Enugu and there is high
      incidence of this cancer even in young women below the age of 30 years. The
      commonest gynaecological cancer in women less than 30 years is choriocarcinoma,
      and anaemia is the commonest sequelae of all gynaecological cancers.

PMID- 21970242
TI  - Jadelle subdermal implants. Preliminary experience in a teaching hospital in the
      Niger Delta Region of Nigeria.
AB  - BACKGROUND: The reproductive health hazards of unwanted pregnancies and unsafe
      abortions have been reduced with modern contraceptive use. The purpose of this
      review is to highlight the acceptability and side effects of Jadelle; a modern
      subdermal contraceptive implant in Port Harcourt. METHODS: Case files of
      acceptors of Jadelle:" subdermal implants between 4th January 2008 and 30th June
      2010 were retrieved. Information obtained were sociodemographic characteristics,
      insertion and post insertion complications. Data analysis was done with Microsoft
      Excel and EPI info statistical software 14.0. RESULTS: Of the seven thousand,
      eight hundred and eighty four (7884) clients who accepted contraceptive during
      the study period; 75 chose Jadelle constituting 0.95% of acceptors. The mean age
      and parity of acceptors were 33.1 years and 4.05 respectfully. Majority of the
      clients (89.33%) were married while 10.67% were single mothers. Similarly most of
      the acceptors had secondary and tertiary education, 26.67% and 69.33%
      respectively. Prevalent side effects were amenorrhoea (41.33%), intermenstrual
      bleeding (6.67%), intermenstrual spotting (4.00%). None of the acceptors
      discontinued the method. There was no accidental pregnancy. CONCLUSION: Jadelle
      appears to have been accepted in our centre. About two third of the clients
      switched from their other methods to Jadelle; with a zero percent
      discontinuations rate among acceptors.

PMID- 21970243
TI  - Accidental tear gas injuries in security agents.
AB  - BACKGROUND: Tear gas is a noxious vapour used in quelling civil disturbances. The
      law enforcement agents who usually handle this are well trained and rarely
      injured by the use of this weapon especially during peace times. METHODS: We
      report injuries sustained by two policemen handling tear gas as a result of
      accidents. Case notes of the patients were the source of information. RESULTS:
      Two policemen were injured while handling tear gas. The equipment accidentally
      dropped and exploded on attempting to pick them. The mechanisms of injuries and
      parts of the body injured were similar ie the hands and face with traumatic
      cataract of an eye in one patient. CONCLUSION: We conclude that proper training
      of the law enforcement agents will go a long way in reducing these types of
      morbidity from tear gas use.

PMID- 21970244
TI  - A rare case of orofacial blast injuries caused by explosion of dry cell batteries
      in a 12-year-old Nigerian.
AB  - BACKGROUND: Severe isolated facial injuries arising from the explosion of dry
      cell battery in children is extremely rare. The management of the resultant
      tissue devastation in a scarce resource economy can be quite challenging. METHOD:
      We report a case of 12 year old boy who sustained extensive oral and facial blast
      injuries caused by shattering of a locally assembled fan as result of an
      explosion of four 1.5 Volts dry cell batteries. He had multiple lacerations and
      avulsion of facial soft tissues as well avulsion and fractures of the mandible
      and maxilla. There was associated oronasal communication and avulsion of the
      anterior teeth in the upper and lowerj aws. RESULTS: Serial debridement and
      minimal repair of soft tissue injuries as well as splinting of the mandible was
      done under local anaeasthesia. Fourteen months after the injuries there was
      complete healing of mandibular fracture and closure of the oronasal
      communication. However patient had perioral hypertrophic scar, microstomia and
      edentulism. CONCLUSION: Extensive life threatening injuries can be caused by a
      simple device such as a 1.5v dry cell battery. Early surgical intervention offers
      the best hope for full recovery.

PMID- 21970245
TI  - Mixed strokes: (three case reports) with literature review.

PMID- 21970246
TI  - Chronic thromboembolic pulmonary hypertension with pulmonary infarction occuring
      in a hypertensive.
AB  - We present a 72-year-old man and a known hypertensive with poor drug compliance
      seen here on 22-03-06,with a 4-year history of progressive dyspnoea, associated
      with cough and a wheeze. On examination he was chronically ill looking with
      altered state of consciousness, pale, centrally cyanosed, febrile (T-38 degrees
      C), in respiratory distress (RR-33pm). Significant chest radiological findings
      include marked aortic unfolding and cardiomegaly, with biventricular involvement.
      Numerous nodular opacities in both lung fields especially the Right side with
      right apical opacification/thickening. Treatment as appropriate was instituted
      but unfortunately the patient succumbed after thirty days on admission and an
      autopsy carried out revealed multiple pulmonary infarcts with pulmonary thrombo
      embolism.

PMID- 21970247
TI  - Presumed idiopathic intracranial hypertension: A case report and literature
      review.
AB  - BACKGROUND: Idiopathic intracranial hypertension is a rare neurologic disorder
      which is largely self limiting and occurs as a result of increased intracranial
      pressure. Papilloedema is the most significant finding and may progress to visual
      loss. CASE REPORT: The case of a 45 year old obese female, who presented with a 9
      month old history of headache and on examination was found to have papilloedema
      is presented here. The patient received no medical or surgical intervention and
      presented 5 months later with resolution of the symptoms. CONCLUSION: Idiopathic
      intracranial hypertension is a sight threatening disease in which raised
      intracranial pressure is associated with increased body mass index. Proper
      assessment and close monitoring of patients who present with these features is
      essential in preventing visual loss.

PMID- 21970248
TI  - Perforated peptic ulcer (PPU) in pregnancy during Ramadan fasting.
AB  - BACKGROUND: Perforated Peptic Ulcer (PPU) is extremely rare in pregnancy. We
      report a case of perforated peptic ulcer in pregnancy during Ramadan fasting.
      PATIENT AND METHODS: The patient is a 16 years old primigravida who presented
      with features of peritonitis at 28weeks of gestation while fasting during
      Ramadan. Ultrasound scan reported a singleton live fetus at 28 weeks gestation.
      At laparotomy via upper midline incision; a 1 cm roundish perforation located on
      the duodenum anteriorly was found with about a litre of gastric juice mixed with
      blood and food particles in the peritoneal cavity. The perforation was close
      transversely with omental patch (Modified Graham's patch) and peritoneal lavage
      done with warm saline. She had a preterm delivery of a 1 kg baby 3 days post
      operatively by a spontaneous vaginal delivery, but the baby died 3 days later.
      CONCLUSIONS: Perforated Peptic Ulcer(PPU) though rare in pregnancy can occur and
      fasting can be a risk factor.

PMID- 21970249
TI  - Approach to positioning special patients when doing cataract surgery in a
      resource poor setting.

PMID- 21970252
TI  - Medical profession: what is in the name?

PMID- 21970253
TI  - Pterygium: A review of clinical features and surgical treatment.
AB  - BACKGROUND: Ptergium is a frequently encountered clinical entity in ophthalmic
      practice. Although commoner in the tropics compared with the temperate region,
      all Ophthalmologists worldwide should be conversant with the clinical features
      and outcome of various approaches to surgical management. A review of the
      efficacy of the currently available surgical procedures for pterygium excision
      using postoperative recurrences as the main outcome measure is presented. METHOD:
      Manual and electronic (PUBMED, MEDLINE, AJOL AND HINARI) search for medical
      literature relevant to clinical features and surgical treatment of pterygium was
      conducted. Previous reviews, large case series reports, randomized controlled
      trials and one meta-analysis were selected and critically reviewed. RESULTS:
      Postoperative recurrence is a dominant complication of pterygium excision
      irrespective of the adopted surgical procedure. Pterygium excision with
      adjunctive therapy and ocular surface reconstruction is the current procedure of
      choice in view of its comparatively higher efficacy in preventing recurrence.
      CONCLUSION: Recurrence is the commonest postoperative complication of pterygium
      excision. There is need for further research into the aetiopathogenesis and risk
      factors for recurrence of human pterygia.

PMID- 21970250
TI  - Potential advantages of topical phenytoin as a novel anti psoriasis arsenal.

PMID- 21970254
TI  - Which feeding option is safer for the HIV exposed infant in sub-Saharan Africa? A
      critical appraisal of randomized controlled trials.
AB  - BACKGROUND: Breast milk is a source of optimal nutrition and protection against
      serious infectious childhood diseases, but carries with it the risk of
      transmission of the HIV virus to the infant. Therefore, to breast feed or not,
      remains a dilemma for the HIV positive woman in sub-Saharan Africa. This
      manuscript critically examines findings from randomized controlled trials to draw
      evidence available on infant feeding options for HIV exposed infants in sub
      Saharan Africa. METHODOLOGY: Primary literature was search on Pub med with the
      following MeSH terms-"Breastfeeding"; "HIV"; "Infant Formula"; and "sub-Saharan
      Africa". Randomized Controlled Trials on infant feeding strategies done in sub
      Saharan Africa with clinicaltrial.gov registration numbers, published between
      2000 and 2009 were eligible for review. The main outcome assessed was postnatal
      HIV transmission rates, HIV-free survival and infant mortality. RESULTS: A total
      of 9 randomized controlled trials were assessed for eligibility and 4 fulfilled
      the inclusion criteria for review. Evidence drawn from the findings of four out
      of 9 (4/9) randomized controlled trials done in sub-Saharan Africa settings
      supports breastfeeding as an optimal and safe option for the HIV exposed infant
      in most settings of sub-Saharan Africa faced with challenges of poor access to
      clean portable water and other socioeconomic limitations. The various study
      settings, main outcome measures and the principal findings and conclusions are
      summarised in table 1. CONCLUSION: The findings from the various randomized
      controlled trials in this review support the practice of breastfeeding with
      antiretroviral therapy to the mother as a safer option for the HIV-exposed infant
      in sub-SaharanAfrica.

PMID- 21970255
TI  - Gender issues in reproductive health: a review.
AB  - Gender, for its impact on virtually every contemporary life issue, can rightly be
      regarded as a foremost component of reproductive health. Reproductive health
      basically emphasises on people and their rights to sexuality, reproduction, and
      family planning, and the information to actualize these right, which has been
      inextricably linked to development at the International Conference on Population
      and Development (ICPD) held in Cairo, Egypt, in 1994. Women's sexual and
      reproductive rights became recognised as universal human right, violations of
      which occur in some reproductive health areas including gender concerns. Gender
      inequality and inequity encompass gender based violence as well as gender
      discrimination which cuts across the life cycle of the woman; attitudes,
      religious and cultural practices of various nations; and issues related to
      employment, economy, politics, and development. The redress of gender inequality
      is a collective responsibility of nations and supranational agencies. Nations
      should adopt a framework hinged on three pedestals--legal, institutional and
      policy, employing the three recommended approaches of equal treatment, positive
      action, and gender mainstreaming.

PMID- 21970256
TI  - Audiometric findings in Waardenburg's syndrome amongst the institutionalised
      deaf/blind in Kaduna-Nigeria.
AB  - INTRODUCTION: Waardenburg's syndrome (WS) is a rare inherited disorder of
      congenital hearing loss and Pigmentary disturbances of the eyes, hair, skin and
      neural crest derivatives. MATERIALS & METHODS: 620 students in a deaf/blind
      school were examined and four had WS with a frequency of 0.65%. 2 males and 2
      females with WS and age ranges between 10-19yrs {mean 15.75yrs.} All 4 subjects
      had complete blue irides, white forelock and sensorineural hearing loss, and thus
      met the diagnostic criteria. They were then subjected to Audiometric assessment.
      RESULTS: Otoscopy was essentially normal but Audiometry revealed sensorineural
      hearing loss [SNHL] in all the subjects ranging from severe to profound with one
      subject being stone deaf. CONCLUSION: WS is a rare disorder in our environment
      although it may be under reported. Two ofthe subjects benefited from
      amplification and were given hearing Aids. Provision of early amplification
      cannot be over emphasized.

PMID- 21970257
TI  - Canthal and cephalic indexes of children with homozygous sickle cell disease in
      Port-Harcourt.
AB  - INTRODUCTION: This research was conducted in view of the importance of
      anthropometric indices of the head and face in forensic medicine, surgery,
      paediatrics and medical imaging. This study was put forward to determine some of
      the effects of chronic diseases on head and face of children with homozygous
      sickle cell disease. METHOD: A comparative study on canthal and cephalic indexes
      were carried out on 100 patients, 54 males and 46 females who are homozygous for
      sickle cell anaemia, who attended the sickle cell clinic at the University of
      Port-HarcourtTeaching Hospital between the age ranges of 3-18 years. The same was
      also done for 500 normal growing children 291 males and 209 females between ages
      3-18 years who are pupils of the University Kindergarten, Demonstration Primary
      and Secondary Schools as well as First International Academy Secondary School,
      Rumuokoro, Port Harcourt. The head length, head breadth, inner and outer canthal
      distances measured. The results showed a mean cephalic index value of 79.89 +/-
      0.87 for the normal growing children while that of the sickle cell children was
      79.54 +/- 2.14, which is not statistically significant (P>0.05). The mean canthal
      index for healthy children was 35.16 +/- 1.01 as against 37.28 +/- 1.65 for the
      sickle cell children, which is statistically significant. CONCLUSION: This
      research determined the possible effects of chronic diseases such as sickle cell
      anaemia on the diversity of head and face shapes in children.

PMID- 21970258
TI  - Rehabilitation of patients with war-related lower limb amputations.
AB  - AIM: To investigate the influence of factors: the amputation type and the time
      lag between last surgery and prosthetic rehabilitation, on the rehabilitation
      duration and outcome, in patients with war-related lower limb amputations.
      METHODS AND SUBJECTS: We reviewed the records of 101 war-related lower limb
      amputees who had inpatient rehabilitation at the National Ortho-Prosthetic Centre
      (NOPC) of Kosovo in Pristina, from July 1999 to June 2001, a retrospective
      observational study. Assessment of rehabilitation outcome-ambulation grade with
      prosthesis, is made on a 3-point scale. RESULTS: The amputation type was shown as
      an important predictor for the rehabilitation duration and outcome. The analysis
      by comparative groups has confirmed the amputation type to be of biggest
      importance. Earlier prosthetic rehabilitation, was shown as a factor of influence
      on the rehabilitation duration in all cases (r=0.22, P=0.027). This predictor was
      not relevant for the rehabilitation outcome. The most frequent type of prosthesis
      manufactured for the amputees, was the patellar tendon bearing below-knee
      prosthesis with suspension band (36.9%). CONCLUSION: Amputation of the limb
      should be performed as low as possible. If there are possibilities for prosthetic
      rehabilitation, any delays must be avoided, particularly in war-related lower
      limb amputees.

PMID- 21970259
TI  - Body size and adiposity indicators and their relationship with blood pressure
      levels in Ibos of Nigeria.
AB  - BACKGROUND: Racial Predisposition to Hypertension, obesity and other
      cardiovascular diseases (CVD) have been the subject of some recent researches.
      The various anthropometric and obesity indicators and their relationship with
      blood pressure parameters in the Ibos of Nigeria were studied. METHOD: Using the
      simple random design, 569 males and females Nigerians of Ibo ethnicity, ages 20
      to 80 years were enrolled for this study. Systolic and diastolic blood pressure
      (SBP & DBP), body mass index (BMI), waist hip ratio (WHR), waist height ratio
      (WHTR), waist circumference (We), triceps, subscapular, calf and sum of three
      skin fold thicknesses (TSF, SSF, eSF,& STS respectively) and other anthropometric
      parameters were measured. RESULT: The mean SBP for the study was 119.6 +/- 23
      mmHg and DBP 79.8 +/- 13mmhg. Males showed higher mean values of 5mmHg in SBP and
      3mmHg in DBP than the females. we was 3cm larger in the females than the males.
      BMI, WHTR, and STS were all larger in the females than in the males. The highest
      level of association noted in the study was between we and WHTR (r = 0.926, P <
      0.01). The levels of correlations of the blood pressure parameters with the
      obesity indices were higher with DBP than SBP. For both sexes; we was the highest
      predictor of DBP, followed by WHTR. Age gave the highest prediction of SBP.
      CONCLUSION: This work notes WHTR as the best predictor of central obesity and
      also a better index for screening CVD risk factors in the Ibos.

PMID- 21970260
TI  - Patients' attitude towards anterior teeth extraction an prosthetic replacement at
      the UPTH Dental Center, Port Harcourt.
AB  - AIM: The purpose of this study was to assess the attitude of patients towards
      anterior teeth extraction and prosthetic replacement of same at the Dental center
      of the University of Port Harcourt Teaching Hospital (UPTH). METHODS: A
      retrospective review of the data of patients who presented for anterior teeth
      extraction and prosthetic replacement or anterior teeth extraction only over a
      two-year period was done using the records of the oral surgery and prosthetic
      clinics of UPTH Dental centre. Demographic and clinical information were
      retrieved and analyzed using the SPSS version 15.0 (SPSS Inc., Chicago, IL, USA).
      RESULTS: Ninety-two patients comprising 58 males(63%) and 34 females (37%),
      giving a male to female ratio of 1.7:1, were involved. The age range was 6 to 86
      years with a median age of 34.5 years. Forty- three patients (46.7%) had both
      extraction and replacement within the study period while 49 patients (53.3%) had
      extraction without replacement. Trauma was the major cause of anterior tooth
      loss, especially among males and young individuals. Plastic removable partial
      denture was the main type of replacement offered. Fifty percent of the females
      (17/34) had replacement compared to 44.8% of the males (26/58). Among those who
      had both extraction and replacement, majority (74.4%, 32/43) requested for
      replacement within a month post extraction. Also, 86.2%t of the patients below 40
      years either had immediate dentures or replacement within a month compared to 50%
      of those above 40 years. CONCLUSION: Most of the patients, surprisingly,
      tolerated anterior edentulousness. However, it appears that anterior
      edentulousness was more abhorent to female patients and younger individuals.

PMID- 21970261
TI  - Seroprevalence of venereal disease among pregnant women attending antenatal care
      (ANC) in Onitsha, Anambra State, Southeast, Nigeria.
AB  - BACKGROUND: Venereal Syphilis if not properly and timely treated has been noted
      to have devastating effects on the fetus and baby. Of all the sexually
      transmitted infections, however, venereal syphilis is one of the most commonly
      screened among antenatal women. This screening is usually limited to the tertiary
      institutions thereby leaving the women who attend private hospitals to a
      disadvantage. OBJECTIVE: This current research is to determine the seroprevalence
      of venereal disease among women attending ANC in an Onitsha specialist private
      hospital and to ascertain the acceptability, and the feasibility of conducting
      the screening in a private setup. METHODS: This cross sectional prospective study
      was conducted among women, who were on their first ANC visit at Grace Specialist
      Hospital, Nkpor, Southeast Nigeria. They were offered VDRL test by ELISA method
      and TPHA confirmation test to those who were seropositive to VDRL test. RESULT:
      Two thousand nine hundred and ninety six women attended antenatal care during the
      study period but 1393 women took part in this study giving an uptake rate of
      46.5%. The seroprevalence rate to venereal syphilis was 0.6%. Three out of the 8
      seropositive results were confirmed with TPHA test. This gives a TPHA/VDRL ratio
      of 0.43. The highest range of occurrence was 25 29years. There was neither a
      significant association between age distribution and VDRL screening result (chi2
      = 1.13; df =5; p = 0.951) nor between parity distribution and VDRL screening
      result (chi2 = 6.2; df = 6; p = 0.4007). Although the seroprevalence of venereal
      syphilis is low but routine universal screening of Venereal syphilis is possible
      in private hospitals and its establishment should be encouraged.

PMID- 21970262
TI  - Clinical presentation and management of schistosomiasis at a hospital in a rural
      area in Nigeria.
AB  - BACKGROUND: Schistosomiasis is a parasitic infection affecting both adults and
      children. It occurs on contact with infected fresh water that harbours the
      intermediate host. It is a chronic disease and its urinary symptoms manifests as
      dysuria and haematuria. METHOD: This is a nine months prospective study of
      patients diagnosed and managed for urinary schistosomiasis at General Hospital
      Aliero, Nigeria from February to October 2006. The patients were followed up
      after presentation and commencement of therapy. RESULT: During the period of
      study, 35 patients were managed at the centre for urinary schistosomiasis. The
      patients presented with haematuria (13), dysuria (12), abdominal pain (4), fever
      (3), oliguria (2), polyuria (1), penile pain (1), and urethral discharge (1). The
      patients were managed with praziquantel. CONCLUSION: Haematuria and dysuria were
      the main symptoms of urinary schistosomiasis. There is need for mass treatment of
      schistosomiaisis in affected areas. Regular continuous education and campaign
      against schistosomiasis is necessary for control ofthe disease.

PMID- 21970263
TI  - Fixation of ankle arthrodesis in a national orthopaedic hospital in Nigeria.
AB  - BACKGROUND: Internal fixation is currently preferred for ankle arthrodesis. There
      are, however, situations in which external fixation is a safer choice. This is a
      five-year retrospective study of ankle arthrodesis to assess the choice,
      technique and outcome of fixation methods used. METHODS: Case notes and
      radiographs of patients with complete records who had ankle arthrodesis between
      January 1st, 2004 and December 31st 2008 were reviewed. RESULTS: Twenty ankle
      arthrodeses in 20 patients were reviewed. External fixation, commonly with
      Charnley's device, was used in 95% of the arthrodeses. Initial alignment was lost
      in 62.5% of arthrodeses with Charnley's device without immediate short leg cast
      support. One tibiotalar arthrodesis done with a single screw had subtalarjoint
      penetration. Fusion and complication rates were 90% and 45% respectively. Foot
      and ankle oedema and pin-tract infection were the commonest complications.
      CONCLUSION: External fixation was more commonly used than internal fixation
      because most of the patients had altered bone anatomy, wounds, active infection,
      or osteopenia. Charnley's device was the most commonly used external fixator and
      incorporating it in a short leg cast immediately after operation might improve
      its rotatory stability. The use of image intensifier is recommended for the
      placement of two crossed tibiotalar screws to avoid subtalar penetration.

PMID- 21970264
TI  - Justification rate for non-obstetric hysterectomies: a study of cases in
      University of Calabar Teaching Hospital, Calabar.
AB  - BACKGROUND: Hysterectomy is a commonly performed major, non obstetric operation.
      It is often the definitive treatment for several pelvic pathologies like uterine
      myoma, utero-vaginal prolapsed, dysfunctional uterine bleeding, cervical
      malignancy and uncontrollable post partum haemorhage. The use of the hysterectomy
      in women sometimes without disease has led to the perception that some of the
      indications for hysterectomy are unjustified. The aim of this study is to
      determine the justification rate for the procedure in the University of Calabar
      Teaching Hospital, Calabar. METHODS: This was a retrospective study of
      hysterectomies done at the University of Calabar Teaching Hospital between
      January 2001 and December 2005. The preoperative indication was compared with the
      pathologist's report after surgery. Hysterectomy was considered justified if the
      pathology report verified the indication for surgery or showed a significant
      alternative pathology. RESULTS: The indication for hysterectomy corresponded with
      the histopathological diagnosis in 76.7% of cases, while in 23.3% cases the
      indication and histopathological diagnosis did not correspond, out of these 3.3%
      of cases had significant alternative pathology. In this study 80% of all
      hysterectomies were justified while it was not justified in 20% of cases.
      CONCLUSION: It is suggested that guidelines aimed at reducing unnecessary
      hysterctomies should be put in place and implemented. This will go a long way in
      improving the justification rate for hysterectomies at our centre, save clients
      resources, improve client satisfaction and quality of care.

PMID- 21970265
TI  - Laryngeal tumours: clinical pattern in Sokoto, Northwestern Nigeria.
AB  - BACKGROUND: Laryngeal tumours may be benign or malignant presenting with
      progressive voice hoarseness and upper airway obstruction which may be
      misdiagnosed. METHOD: Patients were prospectively recruited over 6years from July
      1999 to July 2005 in a tertiary health centre. RESULTS: Thirty seven cases of
      laryngeal tumours were seen (30 males (81.1%), 7 females (18.9%). The incidence
      was 6.2 cases per year. Histological diagnosis was only obtained in 30 patients
      (25 (83.3%) males, 5 females (16.7%). The age range was 3 months to 75 years with
      the mean ages (benign 6.1 years, and malignant 47.9 years). Histology of the 30
      patients showed 20 (66.7%) to be malignant (Squamous cell carcinoma) out of which
      17 (85%) were males and 3 (15%) females with male to female sex ratio of 5.7:1.
      Ten (33.3%) of the 30 cases were benign out of which 8 were males (80%) and 2
      females (20%) with male to female sex ratio of 4:1.Malignant cases who had total
      laryngectomy, selective neck dissection with radiotherapy lived longer (minimum
      of 4 years) than those who had only total laryngectomy (maximum of 2(1/2) years)
      or only radiotherapy (6 months - 1 year). There was recurrent nodal neck lesions
      in 6 (30%) patients, five of which did not go for radiotherapy after surgery
      while one had postoperative radiotherapy. Two of these died from carotid artery
      rupture. Two female patients with malignant tumor who had total laryngectomy had
      babies born through safe vaginal delivery but eventually succumbed to the
      disease. CONCLUSION: There were more malignant (66.7%) laryngeal tumors than
      benign (33.3%) lesions with a male preponderance and strong association with
      cigarette smoking but no alcohol consumption. The mean age for malignant lesions
      was 47.9 years which signifies a considerably younger population while that of
      benign lesion was 6.1 years.

PMID- 21970266
TI  - Prevalence and pattern of cord blood malaria parasitaemia in a general practice
      setting in sub-Saharan Africa.
AB  - AIM: The aim of this study is to determine the prevalence and pattern of
      umbilical cord blood malaria and its association with peripartum maternal malaria
      in a family practice setting in sub Saharan Africa. METHODOLOGY: A prospective
      case study of pregnant women at delivery in a private practice setting in sub
      Saharan Africa. Giemsa stained blood smears of maternal peripheral blood and
      paired umbilical cord blood were examined under light microscope for malaria
      parasites. RESULT: The prevalence of cord blood malaria was 64.6% compared with
      68.8% for maternal blood. The primigravidae had the highest prevalence for both
      umbilical cord malaria parasitaemia (72%) and maternal blood (72%), when compared
      with secondigravidae (61.1%) and other multigravidae > or = 3 (69.8%). The cord
      blood of primigravidae had the -highest mean parasite density, 1360 +/-
      1987.3/microl, compared with secondigravidae (1000 +/- 143) and other
      multigravidae (1037.7 +/- 1951). The study found a significant variation (p< .05)
      between cord blood malaria parasitaemia and maternal blood malaria parasitaemia.
      Cord blood malaria is not a risk factor for low birth weight. In conclusion, the
      primigravidae have the highest prevalence rates for paired cord blood malaria
      parasitaemia and maternal blood as well as the highest mean parasite density for
      the paired samples.

PMID- 21970267
TI  - HIV/AIDS and clinical dentistry: assessment of knowledge and attitude of patients
      attending a university dental centre.
AB  - BACKGROUND: A comprehensive test of knowledge of the public about HIV/AIDS,
      particularly as it relates to dentistry is not common in the literature. The
      objectives of this study are: to determine the current knowledge of dental
      patients about HIV/AIDS and its relationship with clinical dentistry; and to
      determine the general attitude and practice of dental patients as it relates to
      HIV infection. MATERIALS AND METHODS: This clinic study was conducted in the
      outpatient clinics, Dental Centre, University College Hospital, Ibadan. A
      structured anonymous questionnaire was used to collect data from randomly
      selected respondents. The formula n= z2pq/d2 was employed to determine the sample
      size. The items requested includes: educational background, awareness of HIV
      infection and source of knowledge, features of AIDS, high risk groups, HIV
      prognosis and routes of infection. Others include attitudes of respondents to HIV
      epidemics, infected patients, and safe sexual practices. RESULTS: Majority of the
      respondents (96.6%) was aware of HIV infection and the commonest source of
      information was TV and radio. Weight loss was the only feature of AIDS known to
      most of the respondents and only very few of them were aware of oral features
      like bleeding and painful gum (HIV gingivitis) and Kaposi's sarcoma. Most of the
      respondents were not aware that intravenous drug abusers and long distance
      drivers were high risk groups and most were not aware of the types of dental
      procedures during which infection could occur. Most of the respondents were aware
      that HIV infection has a good prognosis and most (64.3%) would like infected
      patients to have a special designated dental clinic for treatment of infected
      persons. Only about one-third use condom regularly or occasionally. CONCLUSION:
      Knowledge of the general and oral features of AIDS, the high risk groups and the
      routes of infection in dental clinical practice were not satisfactory. A cross
      section of the respondents showed negative attitudes to infected patients and
      infection prevention strategies.

PMID- 21970268
TI  - Bacterial isolates in chronic suppurative otitis media: a changing pattern?
AB  - The most frequently isolated organism in chronic suppurative otitis media from
      different parts of the world is Pseudomonas aeruginosa. The pattern from this
      bacteriological study from our region is different. This study was carried out on
      97 patients presenting to the outpatient clinic of the National Ear Care Center,
      Kaduna. Nigeria from May 2008 to April 2009. The patients were aged between 1
      year and 75 years comprising 50) males and 47 females giving a male to female
      ratio of 1:1. Most of the patients (n=40, 41.2%) were in the age group 1-10)
      years. Seventy-five (77.3%) patients had a positive culture while in 22 (22.7%)
      patients there was no growth. Gram-negative bacteria comprised 80% of the
      isolates. The predominant organisms cultured were Klebsiella sp (n=31, 41.3%),
      Escherichia coli (n=22, 29.3%) and Pseudomonas aeruginosa (n=6, 8%). The gram
      positive isolates were Streptococcus sp (n=8, 10.8%) and Staphylococcus aureus
      (n=7, 9.3%). In-vitro drug sensitivity pattern of all isolates shows that they
      were more sensitive to Ofloxacin, ciprofloxacin and Perfloxacin. Klebsiella sp.
      Escherichia coli and Streptococcus sp. are the leading pathogenic organisms in
      chronic suppurative otitis media in our region and their ensitivity rates are
      highest to the quinolone antibiotics, which are relatively cheap, readily
      available as ototopic agents and lack ototoxic effects.

PMID- 21970269
TI  - Common under-five morbidity in South-Eastern Nigeria: a study of its pattern in a
      rural mission general hospital in Imo State.
AB  - BACKGROUND: The under-five children are the most vulnerable group that bears the
      burden of diseases to a large extent in Nigeria. This study was aimed at
      describing the common and pattern of under-five morbidity in a rural Mission
      General Hospital in Imo state, South-Eastern Nigeria. METHODS: A cross sectional
      descriptive hospital-based study was carried out from June 2008 to June 2009 on
      244 under-five children aged 4 days to 58 months. The under-five children seen
      within the study period who met the selection criteria were studied. The data
      collected included age, sex and diagnosis made. RESULTS: One hundred and seven
      (43.8%) out of a total of 244 under-five children studied were aged 37-60 months,
      eighty one (33.2%) were aged 13-36 months and fifty six (23.0%) were aged 0-12
      months. There were 141 (57.8%)males and 103 (42.2%) females. The three commonest
      causes of morbidity were malaria infections (80.3%), acute respiratory infections
      (32.0%) and skin infections (29.1%). The age group 37-60 months bears the
      greatest burden of malaria infections (49.0%), acute respiratory infections
      (55.1%) and skin infections (53.5%). CONCLUSION: This study shows that the three
      commonest causes of under-five morbidity (malaria, acute respiratory infections
      and skin infections) are largely preventable and infectious diseases still
      remaining major causes of morbidity; and similar to the under-five morbidity
      pattern documented at the beginning of the implementation of Primary Health Care
      and Child Survival Strategies in Nigeria. Identification, implementation,
      monitoring and evaluation of multidisciplinary and multisectoral intervention
      strategies targeted at the common under-five morbidity that are culturally
      acceptable, scientifically proven, patient-, family- and community-friendly and
      centred are recommended.

PMID- 21970270
TI  - Survey of pediatric ophthalmic diagnoses in a teaching hospital in Nigeria.
AB  - BACKGROUND: A review of pediatric cases seen over one year in the eye clinic of
      the University of Port Harcourt teaching hospital, Rivers state is presented.
      AIM: To ascertain the different diagnoses made in children who attend the eye
      clinic and the most common with a view to establish guidelines for equipping a
      functional pediatric ophthalmic clinic to address the problems if any.
      METHODOLOGY: Records of all patients aged 0-18 years who attended the clinic in
      the year 2004 were extracted from the outpatient register. The information was
      analyzed manually with a simple scientific calculator. RESULTS: Atotal number of
      846 pediatric patients were seen in the one year period under review. Newly
      diagnosed patients were 671 in number. Male female ratio was 1:1.07. The largest
      number of patients seen was between the ages of 13-18 years (n = 320). Refractive
      error was the most common condition seen with 248 diagnosed with the condition
      and a percentage of(28.95%) of the total number of patients seen. Vernal
      conjunctivitis followed with a percentage of 17.96% (n=152). Sixty-two (7.33%)
      were diagnosed with iritis while 52 were diagnosed to have cataract (6.15%).
      Thirty-five had glaucoma as the primary diagnosis (4.14%) while 14 children
      presented with conjunctivitis (1.65%). Other patients had pterygium (n=9, 1.06%),
      chalazion (n=4, 0.47%) and corneal opacity (n=6, 0.71%). The patients with
      refractive error and vernal conjunctivitis were mainly girls 56.5% and 25%
      respectively. Glaucoma mainly affected boys (57.1%) Cataracts were mainly seen in
      girls (53.8%). CONCLUSION: The commonest causes of childhood ocular morbidity in
      this study were refractive error and allergic conjunctivitis accounting for
      almost 50% of pediatric patients presenting at the ophthalmology clinic of UPTH.
      These require prompt pediatric ophthalmic consultation for effective treatment
      and prevention of avoidable sequelae. Therefore facilities need to be made
      available to adequately detect these conditions early particularly for refractive
      errors before amblyopia develops through training of teachers in all schools and
      public awareness campaigns. It may be important to ensure that legislation be
      passed to ensure compulsory eye checks before parents enroll their wards in
      school.

PMID- 21970271
TI  - Morbidity and mortality pattern of admissions into the Emergency Paediatric Unit
      of University of Abuja Teaching Hospital, Gwagwalada.
AB  - BACKGROUND: Emergency paediatric unit (EPU) is a key service area in many
      tertiary health institutions. The concept of performance evaluation in the
      hospital is an indispensible tool for evaluating the health care service rendered
      to the populace, generation of base line data for comparative purposes, policy
      formulation as well as planning for health care operatives. Since the inception
      of the University of Abuja Teaching Hospital (UATH) in 1983, there has been no
      comprehensive review of performance activities in this very important key service
      area of the hospital. OBJECTIVE: The aim of this study was to determine the
      pattern and outcome of admissions into of the EPU of the hospital. METHODS: A
      review of all admissions into the EPU of UATH over one year was carried out to
      determine the pattern ofmorbidity and mortality in the unit. The data retrieved
      from the Medical Records Department of the hospital of all children admitted into
      the EPU between January and December 2008 included sex, age, body weight,
      diagnosis, number of days on admission, and outcome ofadmission. RESULTS: Six
      hundred patients were admitted into the unit during the review period. The three
      leading causes of admissions were severe anaemia from severe malaria (14.7%),
      pneumonia (13.8%) and gastroenteritis (11.2%); while the least causes were
      surgical conditions (0.8%), bone/soft tissue disorders (1.5%) and renal
      conditions (1.5%). Children less than five years were responsible for 80.1% of
      all admissions, while those less than two years accounted for 56.8% and infants
      less than one year (30.8%). Diarrhoeal disease (20.0%), severe anaemia from
      severe malaria (12.6%), malnutrition (11.6%), were the three major causes of
      mortality in children in the present review. Although meningitis was among the
      least causes of admission, it however caused the highest mortality of 45.5% per
      disease entity. The overall mortality rate in this study was 15.8%. CONCLUSION:
      The vulnerability of under-five years to both infectious and nutritional
      disorders are highlighted in this study and underscores the importance of
      strengthening and sustaining the existing childhood preventive programmes.
      Improving the wellbeing of the populace, as well as health education and disease
      surveillance will help in reduction of these disorders in children.

PMID- 21970272
TI  - Farm-related ocular trauma in Makurdi, Nigeria.
AB  - BACKGROUND: Benue State, Nigeria, is largely an agrarian community. Farm related
      ocular injuries abound in this environment. Approximately two-third of all
      patients presenting to the eye casualty department do so because of ocular trauma
      sustained on the farm. This study aims to study the pattern and burden of farm
      related ocular injuries and its consequences and institute appropriate measures
      that will minimize visual loss from such injuries. METHODS: A retrospective
      analysis of 1560 patients' record treated for ocular injuries between June 2000
      and May 2005. The biodata extracted for each patient included age, sex,
      occupation, cause of injury, ongoing activities at time of injuries, severity of
      injury, time interval before presentation and entry and exit visual acuity.
      RESULTS AND CONCLUSION: Result showed that of the 1560 patients' record audited,
      1113 (71%) were male and 447 (29%) female. Their age ranged between 2 and 75
      years with peak age incidence in the 2nd and 3rd decades. More than two-third of
      all ocular injuries were sustained in the farm environment with spear-grass
      corneal abrasion being the most common lesion. Only 25% presented for attention
      on the day of injury. On presentation, 55% presented with visual impairment, 15%
      presented blind in the affected eye. Closed eye injuries were more common than
      open eye injuries with the former having better prognosis.

PMID- 21970273
TI  - Absolute neutrophil values in malignant patients on cytotoxic chemotherapy.
AB  - A total of eighty patients with various malignancies seen between September 2008
      and April 2009 at the University of Nigeria Teaching Hospital (UNTH) Ituku
      Ozalla, Enugu, Nigeria, had their absolute neutrophil counts, done at Days 0 and
      12 of the first cycle of their various chemotherapeutic regimens. They were adult
      patients who had been diagnosed of various malignancies, consisting of Breast
      cancer 36 (45%), Non-Hodgkin's lymphoma 8 (10%), Hodgkin's lymphoma 13 (16.25%),
      Colorectal carcinoma 6 (7.5%), Multiple myeloma 7 (8.75%), Cervical carcinoma 1
      (1.25%) and other malignancies 9 (11.25%), Manual counting of absolute neutrophil
      count was done using Turks solution and improved Neubauer counting chamber and
      Galen 2000 Olympus microscope. The socio demographic data of the patients were
      assessed from a questionnaire. There were 27 males (33.75%) and 53 females
      (66.25%). Their ages ranged from 18 - 80 years with a median of 45 years. The
      mean absolute neutrophil count of the respondents pre-and post chemotherapy was
      3.7 +/- 2.1 x 10(9)/L and 2.5 +/- 1.6 x 10(9)/L respectively. There were
      significant differences in both the absolute neutrophil count (p=0.00) compared
      to the pre-chemotherapy values. Chemotherapeutic combinations containing
      cyclophosphamide and Adriamycin were observed to cause significant reduction in
      absolute neutrophil.

PMID- 21970274
TI  - Traumatic hip dislocation at a regional trauma centre in Nigeria.
AB  - BACKGROUND: Traumatic dislocation or fracture-dislocation of the hip is an
      orthopaedic emergency that is steadily increasing in incidence due to high-speed
      motor vehicular accidents. These injuries need to be recognized early and
      promptly treated to prevent morbidity and long-term complications. Some of the
      fundamental issues in the management of traumatic dislocations of the hip are the
      critical interval between injury and reduction, the type of reduction most
      suitable for various types of injury and the duration of immobilization that give
      the best results. This study was carried out at the National Orthopaedic Hospital
      Enugu, a regional trauma and orthopaedic centre in South-East Nigeria. The
      purpose of the study is to describe the pattern of presentation and to identify
      the factors that determine the long-term outcome in the treatment of traumatic
      dislocations and fracture-dislocations of the hip at Enugu, Nigeria. METHODS: The
      case notes of all the patients that presented with traumatic dislocations and
      fracture-dislocations of the hip between January 2003 and December 2007 were
      reviewed. The information extracted and analyzed included the patients'
      demographics, etiology of injury, time interval before reduction, associated
      injuries, treatment offered, complications and follow-up. Thompson-Epstein
      classification was used to grade the posterior hip dislocations. The outcome of
      treatment was evaluated using the clinical and radiological criteria proposed by
      Epstein (1974). Three patients with incomplete data and two patients with central
      fracture dislocation were excluded from this study. RESULTS: Forty-eight patients
      with 50 hip dislocations were analyzed. The age range was 12 years to 67 years
      with a mean age of 34.8 years. Thirty-nine patients (81.3%) were males and 9
      (18.7%) were females. Road-traffic accident was the leading cause of traumatic
      hip dislocation in this series, 44 cases (91.6%). Posterior dislocation occurred
      in 48 hips (96%) while anterior dislocation occurred in 2 hips (4%). Forty-seven
      hips (94%) were treated by primary closed reduction, two hips (4%) were treated
      with open reduction and one patient (2%) had Girdlestone excision arthroplasty.
      Thirty-six hips (73.5%) were reduced with 12 hours of the injury. Concomitant
      injuries were found in 37 patients (77%). The follow up period ranged from 10
      months to 36 months with a mean follow up period of 15 months. Post-traumatic
      osteoarthritis occurred in 2 hips (4%) avascular necrosis of the femoral head was
      seen in 2 hips (4%). Five patients had sciatic nerve paresis while there was
      recurrence in one hip. No mortality was recorded. CONCLUSION: Traumatic
      dislocations and fracture-dislocations of the hip are severe injuries caused
      mostly by high-speed motor-vehicular accidents. Young adult males are most
      commonly affected, and there is a high rate of concomitant injuries. Excellent
      results can be achieved by early and stable closed reduction of these injuries
      with immobilization of the affected hips.

PMID- 21970275
TI  - Factors determining compliance to routine iron supplementation in pregnancy at
      the University of Portharcout Teaching Hospital.
AB  - BACKGROUND: Routine intake of iron supplements during pregnancy improves maternal
      health and pregnancy outcomes. This is observed in a background of increased
      availability and compliance to routine antenatal iron supplements. Poor
      compliance arises not only because of patient behavior but also from factors that
      may be out of patient's control. The aim of this study was to determine the
      proportion of patients who comply, the level of compliance with the iron
      prescription given at the antenatal clinic as well as propose interventions aimed
      at increasing compliance amongst the antenatal population. METHODS: A total of
      five hundred antenatal clients were recruited randomly (the 3rd of clients
      presenting to the clinic) during their antenatal visits between 1st May and 30th
      June, 2009 at the UPTH. Prescriptions for iron supplements and folic acid were
      given and they were interviewed using a standard structured questionnaire. Women
      with low or high compliance were asked to explain what influenced their adherence
      to iron supplementation. RESULTS: Overall compliance in this study was 88.0%.
      Women who complied fully were of the perception that good blood level and birth
      weight were beneficial effects of the routine iron supplement. Gastrointestinal
      side effects and forgetfulness were the main reasons for low compliance.

PMID- 21970276
TI  - Post diagnosis reaction, perceived stigma and sexual behaviour of HIV/AIDS
      patients attending Aminu Kano Teaching Hospital, Northern Nigeria.
AB  - BACKGROUND: The process of becoming aware of one's serostatus, immediate and
      delayed responses of the individual, family and community have profound
      implications on health seeking behaviour of PLWHAs especially in developing
      countries. We investigated post-diagnosis reactions, disclosure, perceived
      stigmatization and sexual behaviour of PLWHAs in northern Nigeria. METHODS: A
      triangulation of methods consisting of structured interviewer questionnaire
      administered on 205 respondents and two Focus Group Discussions with PLWHAs
      receiving care at Aminu Kano Teaching Hospital was used. HIV serodiagnosis,
      immediate and delayed reaction to serostatus and responses of family, friends and
      community members were elicited in addition to perceived stigma and sexual
      behaviour. RESULTS: Overall, 111 (54.1%) of the 205 patients were counseled
      before being tested for HIV infection. Majority of women 59 (51.8%) were tested
      and informed during antenatal care or 46 (40.4%) following diagnostic workup for
      symptoms related to AIDS. Most men 69 (75.8%) came to know during diagnostic
      workup or as part of screening for blood transfusion 5 (5.5%). Up to 37.2% of the
      respondents had kept their serostatus secret. Disclosures were more likely to
      mothers (51.9%), sisters (31.0%), brothers (11.0%) and spouses (6.1%). Of all
      respondents, 149 (72.6%) said they were shocked, afraid, angry and sad while 29
      (14.1%) reported being indifferent. A higher proportion of females 68 (59.7%)
      were shocked, sad and angry than males 36 (39.6%) (P<0.05). Significant
      reductions occurred over time in the proportion of patients that were sad, afraid
      and shocked (P<0.05). A higher proportion of mothers (67.0%), sisters (44.2%),
      friends of the same sex (37.1%), father (27.5%) and spouse (23.7%) were perceived
      to be sympathetic compared to others (P<0.05). Forty-five (21 .9%) of the
      respondents were discriminated against. Of this, 22 (48.9%) happened at home, 18
      (40.0%) in the workplace and the remaining 17 (37.8%) among friends. Of 85
      (41.5%) that were sexually active, 78 (91.8%) reported protecting their partners
      through use of condoms. CONCLUSION: The sub-optimal counseling resulted in strong
      emotional reactions that threatened the strong social support system of PLWHAs.
      Supportive counseling could improve VCT uptake and well being of PLWHAs in
      northern Nigeria.

PMID- 21970277
TI  - Perception of quality of care in HIV/AIDS programmes among patients in a tertiary
      health care facility in Anambra State.
AB  - BACKGROUND: Continuous quality improvement is linked to the use of timely and
      useful feedback from clients in Human Immuno-deficiency Virus (HIV) care. HIV
      experts and care professionals agree that consumer involvement, such as patient
      satisfaction survey, is an essential part of HIV care and policy making today.
      The introduction ofAnti-Retroviral Treatment (ART) services in Nigeria has
      significantly impacted positively on the overall well being of People Living with
      HIV and Acquired Immune Deficiency Syndrome (PLWHA). However, there is little
      understanding of their satisfaction and perception of quality of care provided.
      Consequently, this study was carried out to assess patients' satisfaction with
      ambulatory HIV/AIDS care in a tertiary health facility in Anambra State. METHODS:
      The study design is cross-sectional. A total of 150 patients from Nnamdi Azikiwe
      University Teaching Hospital (NAUTH), Nnewi were selected using systematic
      sampling technique from the daily AntiRetroviral (ARV) clinic register obtained
      from the medical records department of the centre. Data were collected using a
      structured interviewer-administered questionnaire and analyzed using SPSS version
      13. RESULTS: The mean age of the respondents was 38.3 +/- 9.1. Majority (50.7%)
      of the patients was married, and most of them (74.7%) were semi-skilled workers.
      There was a statistically significant difference in the numbers of those who
      spent >240 naira for transportation to the clinic, compared to those who spent <
      or = 240 naira (98 versus 52). Similarly, the number of subjects that spent >30
      minutes are significantly larger than the number that spent < or = 30 minutes to
      reach the clinic (142 versus 8). Also significantly greater number of
      participants spend >750 naira than those who spend <750 naira on non-HIV related
      laboratory (20 versus 9) tests. PLWHAs in this facility were least satisfied with
      access to care, while they expressed greatest satisfaction with good patient care
      and quality of service by staff. The overall satisfaction score of the subjects
      was 4.04 +/- 0.33. CONCLUSION: HIV patients' overall satisfaction with the
      services provided to them was quite high. Therefore, there is need to sustain the
      current level of quality of care provided to the patients and if possible improve
      upon it. However, efforts should be made to further decentralize ART services to
      make them more accessible to the growing number of PLWHAs needing care and
      support.

PMID- 21970278
TI  - Histopathological analysis of endometrial biopsies in Jos University Teaching
      Hospital (JUTH), Nigeria. A 5-year critical review.
AB  - AIMS: This study is aimed at giving an insight into the pattern and age
      distribution of endometrial analysis as seen at Jos University Teaching Hospital.
      METHODS: This is a retrospective reviewed cases of endometrial biopsies diagnosed
      between January 1998 to December 2002 in the Histopathological Department ofJos
      University Teaching Hospital RESULTS: A review of endometrial biopsies slides
      from 556 patients revealed that pregnancy related diagnosis was the commonest,
      representing 302 (54.3%) of histopathological diagnosis, followed by endometrial
      hyperplasia, accounting for 97 cases (17.5%) and majority of which was
      categorised as mild hyperplasias. Hydatidiform mole, which ranked third,
      constituted 58 (10.4%) of the cases studied. Choriocarcinoma was the leading
      malignancy representing 10 cases (45%) of the malignant tumours and 1.8% of all
      the endometrial biopsies. Endometrial adenocarcinoma, stromal sarcoma and
      metastatic cancer constituted 6 (1.0%), 3 (0.5%) and 3 (0.5%), respectively.
      CONCLUSION: The commonest endometrial pattern seen in JUTH over the study period
      was products of conception which peak in the third decade of life; primary
      malignancies of the endometrium are uncommon in JUTH and they represented just
      about 2%.

PMID- 21970279
TI  - Vaginal discharge: aetiological agents and evaluation of syndromic management in
      Lagos.
AB  - BACKGROUND: The WHO introduced the syndromic management to help in the control of
      STIs in resource-poor settings. This needs to be adapted to local settings taking
      into consideration the prevalence of the various organisms causing STIs. This has
      given rise to a need to validate the algorithm. The study aimed to correlate the
      syndromic management treatment algorithm for vaginal discharge with the
      aetiological diagnosis based on laboratory investigations. Specifically, the
      sensitivity, specificity and positive predictive values of the syndromic
      management against a gold standard laboratory diagnosis were evaluated. METHODS:
      A total of 195 consecutive patients presenting to the study sites with vaginal
      discharge were enrolled in the study. Information on sociodemographic data was
      obtained with the aid of questionnaires. Samples were taken and examined for
      candida, trichomonas, bacterial vaginosis (BV), chlamydia and gonorrheal
      infections, after speculum and vaginal examinations. RESULTS: The sensitivity and
      positive predictive values (PPV) of the syndromic management in detecting vaginal
      infections performed better than corresponding values for cervicitis. The
      algorithm for cervicitis improved on addition of speculum examination (36% and
      32.1% for sensitivity and PPV respectively). CONCLUSION: The study shows that the
      syndromic diagnosis for vaginal discharge fares better for vaginitis, especially
      with addition of speculum examination. The application of syndromic diagnosis for
      cervicitis resulted in omission of patients who had evidence of cervical
      infections by bacteriologic examination.

PMID- 21970280
TI  - Endoscopic glue injection with application of hemostatic clips: a novel method of
      closing a gastro colonic fistula after PEG tube complication.
AB  - Gastrocolonic fistula after percutaneous endoscopic gastrostomy (PEG tube)
      placement is an uncommon but a serious complication of the procedure. These
      fistulous tracts are often fibrotic and require surgical intervention if the
      spontaneous closure fails. We describe development of gastroclonic fistula in an
      old man who presented with history of post feeding diarrhea of 2 weeks duration
      three months after placement of PEG tube. Successful closure of fistulous tract
      was documented after local glue injection and hemostatic clips without any
      complication obviating need of surgery. The patient is on our follow-up for last
      8 months now.

PMID- 21970281
TI  - Lymphangioma of the tongue with macroglossia: a case report.
AB  - Lymphangioma are rare benign lesions of the lymphatic vessels, found mainly in
      the head and neck. Almost all cases of macroglossia in young children are caused
      by lymphangioma of the tongue. Aesthetic, occlusal, functional and psychosocial
      problems may arise as a result of this condition. The preferred treatment is
      surgery but in some cases sclerosant therapy may be used as an adjunct treatment.
      We report a case of lymphangioma of the tongue with macroglossia that was treated
      successfully with a Vshaped anterior glossectomy and discuss the surgical
      considerations.

PMID- 21970282
TI  - Iatrogenic pyogenic spondylodiscitis: a case report and a review of literature.
AB  - BACKGROUND: Iatrogenic Pyogenic Spondylodicitis is a disease not commonly
      reported probably because of the way it is acquired, from the health
      practitioner. METHOD: The case of a 62 year old man that presented in our
      outpatient department with features of spondylodiscitis after several attempts at
      spinal anaesthesia at a rural hospital was reported and the literature reviewed.
      RESULT: The patient showed remarkable improvement few days with parenteral
      antibiotics and made complete recovery subsequently. CONCLUSIONS: Adequate
      asepsis is required for spinal anaesthesia and parenteral antibiotics given
      presumptively following numerous attempts at spinals.

PMID- 21970283
TI  - Intra-tumoral ligation and the injection of sclerosant in the treatment of
      lingual cavernous haemangioma.
AB  - INTRODUCTION: Haemangiomas are developmental vascular abnormalities and more than
      50% of these lesions occur in the head and neck region, with the tongue, buccal
      mucosa, lips and palate most commonly involve. They are considered as harmatomas
      rather than true neoplasms Factors such as patient's age, size and site of lesion
      and the proximity of lesion to vital structure are paramount in the determination
      of the therapeutic approach 7 surgical excision, cryotherapy, injection of feeder
      vessels with sclerosants and embolization of the blood vessels. CASE REPORT: We
      report the management of cavernous haemangioma of the tongue in a 38 year old man
      using intra-tumoral ligation (The Popescu Procedure) and injection of sclerosant
      under general anaesthesia. RESULT: The efficacy of this method lies in the fact
      that it obstructs the vascular channels to and from the entire tumour mass
      leading to progressive atrophy of the vascular endothelia, fibrous hyperplasia
      and the substitution of the angiomatous tissues by a fibroconnective tissue mass
      which initially appears excessive but remodels and produces an acceptable
      appearance which can be further improved by plastic surgery. CONCLUSION: The
      procedure was well tolerated and the patient made excellent recovery. It is
      recommended in our centre where facilities for technologically demanding methods
      are not available.

PMID- 21970284
TI  - Scleral jaundice may be unilateral: a case report.
AB  - Unilateral scleral jaundice is a rare and puzzling clinical phenomenon. Students
      and health practitioners are further bewildered and confounded when confronted
      with this subject during academic sessions, including examinations. This is
      partly attributable to a situation where both trainers and trainees alike rarely
      encounter such a case. We present this case report to draw attention to this rare
      type of sclera jaundice and to proffer explanations for its occurrence.

PMID- 21970285
TI  - Pregnancy-associated pyogenic granuloma of the lip: a case report.
AB  - Pregnancy associated pyogenic granuloma of the oral cavity especially the
      gingivae is not uncommon. However, pyogenic granuloma of the lip associated with
      pregnancy is a very rare clinical condition. A case of a 29 year-old pregnant
      woman (35 weeks gestation) who presented with a pregnancy associated pyogenic
      granuloma of the lower lip is reported. Chronic irritation of the lower lip which
      acts in an unidentified way with high gingival level of active progesterone is
      the suspected pathogenesis. Surgical excision was the treatment of choice, and no
      recurrence was noted.

PMID- 21970286
TI  - Gallbladder perforation complicating typhoid fever: report of two cases.
AB  - BACKGROUND: Gallbladder perforation (GBP) is rare and as a complication of
      typhoid fever is extremely rare. We present two consecutive patients with GBP
      diagnosed incidentally at laparotomy. METHOD: Information on the management of
      two patients with gallbladder perforation seen at Federal Medical Centre Azare in
      June and October 2008 was extracted from their case records. RESULTS: The two
      patients were both males aged 13 years and 16 years. They both presented with
      high fever of more than 2 weeks duration; and abdominal pain and distension. Both
      patients had features of generalised peritonitis. Pre-operative diagnoses of
      typhoid enteric perforation were made based on a positive Widal test. Intra
      operative findings however, were that of bile peritonitis and gallbladder
      perforation. Both had cholecystectomy. Culture of the bile aspirate yielded
      Salmonella typhi. CONCLUSION: Gallbladder perforation secondary to typhoid fever
      should be considered as a differential diagnosis in patients with suspected
      typhoid enteric perforation in typhoid fever endemic region.

PMID- 21970287
TI  - The muscle maker. Protein is an important part of your diet and your body.

PMID- 21970288
TI  - Tasting the rainbow. Good health comes in many colors.

PMID- 21970289
TI  - A winner at life.

PMID- 21970290
TI  - Back to school.

PMID- 21970291
TI  - Weight loss now. The present and future of the quest to be thinner.

PMID- 21970292
TI  - Just enouth dessert.

PMID- 21970293
TI  - High-performance semiconducting nanotube inks: progress and prospects.
AB  - While the potential for high mobility printed semiconducting nanotube inks has
      been clear for over a decade, a myriad of scientific and technological issues has
      prevented commercialization and practical use. One of the most challenging
      scientific problems has been to understand the relationship between the pristine,
      individual nanotube mobility (known to be in the 10,000 cm(2)/V.s range) and the
      as-deposited random network mobility (recently demonstrated in the 100 cm(2)/V.s
      range). An additional significant scientific hurdle has been to understand,
      manage, and ultimately eliminate the effects of metallic nanotubes on the network
      performance, specifically the on/off ratio. Additional scientific progress is
      important in understanding the dependence of nanotube length, diameter, and
      density on device performance. Finally, the development of ink formulations that
      are of practical use in manufacturing is of paramount importance, especially with
      regard to drying time and uniformity, and ultimately, the issue of scalability
      and cost must be addressed. Many of these issues have recently been investigated
      from a phenomenological point of view, and a comprehensive understanding is
      beginning to emerge. In this paper, we present an overview of solution-based
      printed carbon nanotube devices and discuss long-term technology prospects. While
      significant technical challenges still remain, it is clear that the prospects for
      the use of nanotube ink in a myriad of systems is feasible given their unmatched
      mobility and compatibility with heterogeneous integration into a variety of
      applications in printed and flexible electronics.

PMID- 21970294
TI  - Identification of key residues involved in the dimerization of the secretory
      Na(+)-K(+)-2Cl(-) cotransporter NKCC1.
AB  - The "secretory" Na(+)-K(+)-2Cl(-) cotransporter, NKCC1, belongs to the SLC12 gene
      family of electroneutral cation-chloride cotransporters. A number of these
      proteins, including NKCC1 itself, exist as homodimers in the membrane, suggesting
      that this may be a common feature of the SLC12 family. We have previously
      demonstrated that replacing the C-terminus of NKCC1 with that of its close
      homologue NKCC2 produced a fully functional chimeric protein that formed
      homodimers but did not dimerize with NKCC1. Here we employ a novel co
      immunoprecipitation assay to study the dimerization interaction of NKCC1 using
      additional NKCC1/NKCC2 C-terminal chimeras and point mutants. Our results
      indicate that the substitution of a number of regions of the C-terminus of NKCC1
      with the corresponding sequence from NKCC2 results in weakened dimerization with
      wild-type NKCC1, demonstrating that various residues play a role in this
      interaction. Most interestingly, however, we find that the replacement of a
      single NKCC1 residue, G812, with cysteine, the corresponding amino acid in NKCC2,
      results in a point mutant that displays no significant dimerization with the wild
      type protein. In addition to this effect on heterodimer formation, we also find
      that G812 mutants can nevertheless form homodimers but that this interaction can
      be weaker than that observed for wild-type NKCC1. We demonstrate that our results
      are consistent with at least one established mechanism of protein dimer
      formation, that of "domain swapping", as well as with a recently reported crystal
      structure of the C-terminus of a bacterial SLC12 homologue.

PMID- 21970296
TI  - Revolutionising the AIDS response.
AB  - Individual behaviour change interventions and technological approaches to HIV
      prevention can only be effective over time if the broader social environment in
      which health-related decisions are made facilitate their uptake. People need to
      be not only willing but also able to take up and maintain preventive behaviours,
      seek testing, treatment and care for HIV. This paper presents findings and
      recommendations of the Social Drivers Working Group of the aids2031 initiative,
      which focus on how to ensure that efforts to address the root causes of HIV
      vulnerability are integrated into AIDS responses at the national level. Specific
      guidance is given on how to operationalise a structural approach.

PMID- 21970295
TI  - Photoinduced DNA cleavage promoted by two copper(II) complexes of tetracyclines
      and 1,10-phenanthroline.
AB  - In this report, we demonstrate how UV-light exposure can enhance DNA cleavage
      promoted by two copper(II) complexes of tetracyclines and 1,10-phenanthroline
      about 40 times in comparison to nonirradiated conditions. In addition, new
      aspects regarding their DNA binding properties, as well as the mechanism of the
      cleavage reaction, were also investigated.

PMID- 21970297
TI  - Depression and rumination: relation to components of inhibition.
AB  - BACKGROUND: Recent research has demonstrated that depressed individuals show
      impairments in inhibiting irrelevant emotional material, and that these
      impairments are linked to rumination. Cognitive inhibition, however, is not a
      unitary construct but consists of several components which operate at different
      stages of information processing. The present study was designed to assess two
      components of inhibition and examine their relation to depression and rumination
      in a sample of clinically depressed and healthy control participants. METHODS:
      Twenty-two individuals diagnosed with a current depressive episode and 27 never
      disordered control participants completed an Emotional Flanker Task to assess
      individual differences in interference control and a modification of the Working
      Memory Selection Task to assess individual differences in the ability to discard
      no longer relevant emotional material from working memory. Participants completed
      self-report measures to assess depressive symptoms and rumination. RESULTS:
      Clinically depressed compared to control participants showed significantly
      reduced interference control of irrelevant negative information. The groups,
      however, did not differ in their ability to discard no longer relevant negative
      information from working memory. In contrast, rumination was associated with
      difficulty removing no longer relevant negative material from working memory but
      not with deficits in interference control. CONCLUSIONS: Results highlight the
      importance of differentiating among components of inhibition to gain a better
      understanding of cognitive mechanisms underlying depression and rumination.

PMID- 21970304
TI  - Antimicrobial stewardship: opportunities in long-term care homes.

PMID- 21970305
TI  - Treatment of dementia with Lewy bodies and Parkinson's disease dementia.
AB  - Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) account
      for 10-15% of late onset dementias. Key treatment targets include cognitive and
      functional impairments, neuropsychiatric symptoms including intense and
      persistent visual hallucinations, and parkinsonism. Six-month, placebo-controlled
      randomized controlled trials (RCTs) of the cholinesterase inhibitor rivastigmine
      have indicated modest but significant benefits in cognition, function, global
      outcome and neuropsychiatric symptoms in both PDD and DLB. The evidence base for
      other cholinesterase inhibitors from RCTs is inconclusive. More recent RCTs with
      memantine in PDD/DLB patients indicate a benefit with regard to global outcome,
      with some suggestion of a specific benefit with respect to sleep disturbance.
      Given the risk of severe antipsychotic sensitivity reactions, antipsychotics
      should be avoided. A significant proportion of PDD/DLB patients are responsive to
      levodopa, but care needs to be taken with anti-parkinsonian treatments because of
      their potential propensity to exacerbate neuropsychiatric symptoms, particularly
      hallucinations.

PMID- 21970306
TI  - Arterial aging: a review of the pathophysiology and potential for pharmacological
      intervention.
AB  - This review begins with a perspective on the effects of arterial aging on society
      and world events over the past century. Until recently, the use of just one
      technique to measure blood pressure non-invasively limited progress in
      understanding the mechanisms involved and the potential of antihypertensive drug
      therapies. New methods for extracting information from the arterial waveform have
      followed the (re)introduction of arterial tonometry into clinical practice,
      together with mathematical analysis in the frequency and time domains. These new
      methods have exposed the phenomenon of aortic stiffening with age, and early wave
      reflection arising therefrom, and identified it as the major cause of
      cardiovascular degeneration. Such findings point to arterial aging as a logical
      target for the treatment and prevention not only of cardiac, aortic and large
      artery disease, but also of damage to microvessels in the brain and kidney, which
      in turn leads insidiously to dementia and renal failure, respectively.

PMID- 21970307
TI  - Medicare Part D and quality of prescription medication use in older adults.
AB  - In 2006, the US Centers for Medicare and Medicaid Services implemented Medicare
      Part D to provide outpatient prescription drug insurance to disabled and older
      adults. In creating Part D, a key provision to address quality included
      medication therapy management (MTM) programmes designed to increase proper and
      safe use of medications among targeted Part D beneficiaries. A preponderance of
      evidence shows that Part D has increased medication affordability and
      accessibility; however, what remains less clear is whether it has improved the
      quality of medication use and optimized health outcomes. Now in its sixth year,
      Part D is undergoing its first major revision, with the gradual elimination of
      the coverage gap by 2020. Therefore, now is a good time to review the accumulated
      evidence on the impact of Part D and MTM programmes on the quality of medication
      use to help inform future policy decisions and research directions. In this
      review, we found that Part D's net effect on quality of medication use has mainly
      been positive. Cost-related medication nonadherence improved moderately and there
      were fewer than expected treatment interruptions. However, vulnerable subgroups,
      such as sicker and dual-eligible beneficiaries, experienced lags in improvement.
      Beneficiaries who entered the coverage gap consistently experienced interruptions
      and displayed worsening medication adherence after entering the gap, with generic
      only gap drug coverage offering limited benefit. Such findings can serve as
      baseline information as the coverage gap phases out. Limited availability of data
      is the greatest barrier to research into Part D. Part D's overall effect on
      health outcomes and adverse medical events, such as hospitalizations, is
      inconclusive because of inadequate evidence to date. Similarly, no evaluation of
      quality of medication use is available with respect to utilization management
      strategies and MTM programmes delivered under Part D. Future research will need
      to further examine the added value of Part D and address whether Part D optimizes
      health outcomes in the Medicare population. As the current economic recession
      increases the pressure to cut costs, the effect of future spending restrictions,
      such as restrictions on coverage subsidies, will also be of special concern.

PMID- 21970308
TI  - Parenteral versus oral administration of systemic antimicrobials in European
      nursing homes: a point-prevalence survey.
AB  - BACKGROUND: Residents in long-term care facilities are predisposed to healthcare
      associated infections that are likely caused by antimicrobial-resistant micro
      organisms. Long-term care facilities are increasingly able to offer parenteral
      antimicrobial treatment but there are few data on the use and appropriateness of
      such treatment in this setting. Information on the use of parenteral
      antimicrobials and associated factors in long-term care facilities is necessary
      to assess the risks and benefits of this treatment and to support the development
      of antimicrobial policies aimed at minimizing the emergence and spread of
      antimicrobial resistance. OBJECTIVE: The aim of this study was to describe the
      extent of parenteral and oral antimicrobial use in participating European nursing
      homes (NHs) and to analyse the resident characteristics and determinants
      associated with route of antimicrobial administration. METHODS: Data on resident
      characteristics and antimicrobials were collected by means of a point-prevalence
      survey. Logistic regression was used to analyse the data. RESULTS: Based on data
      from 21 European countries for 2046 antimicrobial prescriptions, an average of
      9.0% (range by country: 0.0-66.7%) of treatment was administered parenterally.
      Multivariate analysis showed that residents receiving parenteral antimicrobials
      had greater morbidity, such as increased risk of having a urinary catheter (p <
      0.001), a vascular catheter (p < 0.001), impaired mobility (p = 0.007) and
      disorientation (p = 0.005). Residents receiving parenteral antimicrobials also
      had been admitted more recently into the NH (p = 0.007). Empirical treatment of
      respiratory tract infections (RTIs) accounted for the majority of parenteral
      antimicrobials, while prophylaxis of urinary tract infection (UTI) was the most
      common indication for oral antimicrobials. Beta-lactam antibacterials
      (cephalosporins and aminopenicillins) were the predominant classes used.
      CONCLUSIONS: Our study showed that risk and care-load factors (i.e. the presence
      of a urinary or vascular catheter, impaired mobility, disorientation and
      relatively short length of stay) were associated with parenteral administration
      of antimicrobials in NHs. Furthermore, both the indication and the class of
      antimicrobial agent used were associated with administration route. For empirical
      treatment of RTIs, antimicrobials were most often administered parenterally.

PMID- 21970309
TI  - Antimicrobial prescribing in nursing homes in Northern Ireland: results of two
      point-prevalence surveys.
AB  - BACKGROUND: In 2005, the European Commission recommended that all member states
      should establish or strengthen surveillance systems for monitoring the use of
      antimicrobial agents. There is no evidence in the literature of any surveillance
      studies having been specifically conducted in nursing homes (NHs) in Northern
      Ireland (NI). OBJECTIVE: The aim of this study was to determine the prevalence of
      antimicrobial prescribing and its relationship with certain factors (e.g.
      indwelling urinary catheterization, urinary incontinence, disorientation, etc.)
      in NH residents in NI. METHODS: This project was carried out in NI as part of a
      wider European study under the protocols of the European Surveillance of
      Antimicrobial Consumption group. Two point-prevalence surveys (PPSs) were
      conducted in 30 NHs in April and November 2009. Data were obtained from nursing
      notes, medication administration records and staff in relation to antimicrobial
      prescribing, facility and resident characteristics and were analysed
      descriptively. RESULTS: The point prevalence of antimicrobial prescribing was
      13.2% in April 2009 and 10.7% in November 2009, with a 10-fold difference
      existing between the NHs with the highest and lowest antimicrobial prescribing
      prevalence during both PPSs. The same NH had the highest rate of antimicrobial
      prescribing during both April (30.6%) and November (26.0%). The group of
      antimicrobials most commonly prescribed was the penicillins (April 28.6%,
      November 27.5%) whilst the most prevalent individual antimicrobial prescribed was
      trimethoprim (April 21.3%, November 24.3%). The majority of antimicrobials were
      prescribed for the purpose of preventing urinary tract infections (UTIs) in both
      April (37.8%) and in November (46.7%), with 5% of all participating residents
      being prescribed an antimicrobial for this reason. Some (20%) antimicrobials were
      prescribed at inappropriate doses, particularly those which were used for the
      purpose of preventing UTIs. Indwelling urinary catheterization and wounds were
      significant risk factors for antimicrobial use in April [odds ratio {OR} (95% CI)
      2.0 (1.1, 3.5) and 1.8 (1.1, 3.0), respectively] but not in November 2009 [OR
      (95% CI) 1.6 (0.8, 3.2) and 1.2 (0.7, 2.2), respectively]. Other resident
      factors, e.g. disorientation, immobility and incontinence, were not associated
      with antimicrobial use. Furthermore, none of the NH characteristics investigated
      (e.g. number of beds, hospitalization episodes, number of general practitioners,
      etc.) were found to be associated with antimicrobial use in either April or
      November 2009. CONCLUSIONS: This study has identified a high overall rate of
      antimicrobial use in NHs in NI, with variability evident both within and between
      homes. More research is needed to understand which factors influence
      antimicrobial use and to determine the appropriateness of antimicrobial
      prescribing in this population in general and more specifically in the management
      of recurrent UTIs.

PMID- 21970310
TI  - Determination of digoxin clearance in Japanese elderly patients for optimization
      of drug therapy: a population pharmacokinetics analysis using nonlinear mixed
      effects modelling.
AB  - BACKGROUND: Optimal use of digoxin in the elderly population requires information
      about the drug's pharmacokinetics and the influence of various factors on the
      drug's disposition. However, because of sampling restrictions, it is often
      difficult to perform traditional pharmacokinetic studies in elderly patients.
      OBJECTIVE: This study was conducted to determine the apparent total clearance of
      digoxin from serum after oral administration (CL/F) and to establish the role of
      patient characteristics in estimating doses of digoxin for elderly patients (age
      >=65 years), using routine therapeutic drug monitoring data. METHODS: Analyses of
      the pharmacokinetics of digoxin were conducted using the nonlinear mixed-effects
      modelling (NONMEM(r)) software, a computer program designed to analyse
      pharmacokinetics in study populations by allowing pooling of data. Steady-state
      data (140 observations) obtained by routine therapeutic drug monitoring following
      repeated oral administration of digoxin in 94 hospitalized elderly patients (age
      >=65 years) were analysed to establish the role of patient characteristics in
      estimating doses of digoxin for elderly patients. RESULTS: Estimates generated by
      NONMEM(r) indicated that digoxin CL/F was influenced by the demographic variables
      of total bodyweight (TBW), serum creatinine (SCr), age (AGE), presence of
      congestive heart failure (CHF), concomitant administration of the calcium channel
      antagonists (calcium channel blockers [CCBs]: verapamil, diltiazem or
      nifedipine), sex (SEX) and elderly clearance factor (trough serum concentration
      of digoxin; [C(trough)] theta). The full version of the final NONMEM(r) model was
      where CCB is 1 for concomitant administration of a CCB and is 0 otherwise; CHF is
      1 for patients with CHF and is 0 otherwise; SEX is 0 for male and is 1 for
      female; and the elderly clearance factor C(trough)-0.180 is 1 for digoxin
      C(trough) <1.7 ng/mL. CONCLUSIONS: We developed a new model for elderly patient
      dosing of digoxin with good predictive performance. Clinical application of the
      findings of the present study to patient care may permit selection of an
      appropriate initial digoxin maintenance dose, thus enabling the clinician to
      achieve a desired therapeutic effect. However, the digoxin dosage regimen should
      be based on an appraisal of the individual patient's clinical need for the drug.

PMID- 21970311
TI  - Silodosin in the treatment of the signs and symptoms of benign prostatic
      hyperplasia: profile report.

PMID- 21970312
TI  - Might pentoxifylline have a role as adjuvant therapy for patients with giant cell
      arteritis?

PMID- 21970313
TI  - Templated synthesis of glycoluril hexamer and monofunctionalized cucurbit[6]uril
      derivatives.
AB  - We report that the p-xylylenediammonium ion (11) acts as a template in the
      cucurbit[n]uril forming reaction that biases the reaction toward the production
      of methylene bridged glycoluril hexamer (6C) and bis-nor-seco-CB[10]. Hexamer 6C
      is readily available on the gram scale by a one step synthetic procedure that
      avoids chromatography. Hexamer 6C undergoes macrocylization with (substituted)
      phthalaldehydes 12, 14, 15, and 18-in 9 M H(2)SO(4) or concd HCl at room
      temperature to deliver monofunctionalized CB[6] derivatives 13, 16, 17, and 19
      that are poised for further functionalization reactions. The kinetics of the
      macrocyclization reaction between hexamer and formaldehyde or phthalaldehyde
      depends on the presence and identity of ammonium ions as templates. p
      Xylylenediammonium ion (11) which barely fits inside CB[6] sized cavities acts as
      a negative template which slows down transformation of 6C and paraformaldehyde
      into CB[6]. In contrast, 11 and hexanediammonium ion (20) act as a positive
      template that promotes the macrocyclization reaction between 6C and 12 to deliver
      (+/-)-21 as a key intermediate along the mechanistic pathway to CB[6]
      derivatives. Naphthalene-CB[6] derivative 19 which contains both fluorophore and
      ureidyl C?O metal-ion (e.g., Eu(3+)) binding sites forms the basis for a
      fluorescence turn-on assay for suitable ammonium ions (e.g., hexanediammonium ion
      and histamine).

PMID- 21970314
TI  - Severe sepsis caused by Aeromonas hydrophila in a patient using tocilizumab: a
      case report.
AB  - INTRODUCTION: Aeromonas species do not commonly cause disease in humans. However,
      when disease is seen, it often occurs in patients with underlying
      immunosuppression or malignancy and has a high fatality rate. CASE PRESENTATION:
      A 72-year-old Japanese woman with rheumatoid arthritis treated with tocilizumab
      (which has an immunosuppressive effect) presented with severe epigastric pain.
      She had a fever with chills, hypotension and jaundice. She was diagnosed with
      acute suppurative cholangitis and treated with cefoperazone-sulbactam and an
      endoscopic drainage was performed. Jaundice was slightly improved, but the shock
      state and inflammatory reactions were prolonged as typical of septic shock. On
      the second day after admission, an electrocardiogram showed ST segment elevation
      and echocardiography showed ventricular wall dysfunction. Coronary arteries were
      patent in coronary angiography and she was diagnosed with stress-induced
      cardiomyopathy. Blood cultures showed Aeromonas hydrophila. A stool culture was
      negative for A. hydrophila. On day six, her white blood cell count and
      neutrophils were normalized and cefoperazone-sulbactam treatment was halted. Left
      ventricular function normalized on day twelve and a laparoscopic cholecystectomy
      for cholelithiasis was performed on the 16th day of hospitalization. A culture
      from the bile showed A. hydrophila. Eighteen days after surgery, tocilizumab
      treatment was restarted and there were no complications. Two months after
      restarting tocilizumab, our patient is stable without any serious events.
      CONCLUSION: We present a rare case of A. hydrophila sepsis and acute suppurative
      cholangitis in an elderly patient with gallstones and rheumatoid arthritis using
      tocilizumab. This clinical course may suggest that preemptive treatment for
      cholelithiasis prior to using molecular-targeting agents might be feasible in
      elderly patients.

PMID- 21970315
TI  - Nonlinear optical properties of type I collagen fibers studied by polarization
      dependent second harmonic generation microscopy.
AB  - Collagen (type I) fibers are readily visualized with second harmonic generation
      (SHG) microscopy though the molecular origin of the signal has not yet been
      elucidated. In this study, the molecular origin of SHG from type I collagen is
      investigated using the time-dependent coupled perturbed Hartree-Fock calculations
      of the hyperpolarizibilities of glycine, proline, and hydroxyproline. Two
      effective nonlinear dipoles are found to orient in-the-plane of the amino acids,
      with one of the dipoles aligning close to the pitch orientation in the triple
      helix, which provides the dominant contribution to the SHG polarization
      properties. The calculated hyperpolarizability tensor element ratios for the
      collagen triple-helix models: [(Gly3)n]3, [(Gly-Pro2)n]3, and [(Gly-Pro-Hyp)n]3,
      are used to predict the second-order nonlinear susceptibility ratios,
      chi(zzz)(2)/chi(iiz)(2) and chi(zii)(2)/chi(iiz)(2) of collagen fibers. From SHG
      microscopy polarization in, polarization out (PIPO) measurements of type I
      collagen in human lung tissue, a theoretical method is used to extract the triple
      helix orientation angle with respect to the collagen fiber. The study shows the
      dominant role of amino acid orientation in the triple-helix for determining the
      polarization properties of SHG and provides a method for determining the triple
      helix orientation angle in the collagen fibers.

PMID- 21970316
TI  - Self-complementary recognition of supramolecular urea-aminotriazines in solution
      and on surfaces.
AB  - The recognition of self-complementary quadruple urea-aminotriazine (UAT)-based
      hydrogen-bonded arrays was investigated in solution and at surfaces. For this
      purpose, an UAT-based donor-acceptor-donor-acceptor (DADA) array and
      complementary receptors were synthesized. Two-dimensional proton nuclear magnetic
      resonance ((1)H NMR) measurements in CDCl(3) pointed at an intramolecular
      hydrogen-bond stabilization of the UAT, which promotes a planar molecular
      geometry and, thereby, results in a significant stabilization of the dimeric
      complex. The bond strength of the UAT dimers at surfaces was determined by atomic
      force microscopy-based single molecule force spectroscopy (AFM-SMFS) in
      hexadecane. The UAT receptor was immobilized on gold surfaces using an ultrathin
      layer of ethylene glycol terminated lipoic acid and isocyanate chemistry. The
      layers obtained and the reversible self-complementary recognition were thoroughly
      characterized with contact angle measurements, grazing angle Fourier transform
      infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), and AFM.
      Loading rate-dependent SMFS measurements yielded a barrier width x(beta) and a
      bond lifetime at zero force t(off)(0) of 0.29 +/- 0.02 nm and 100 +/- 80 ms,
      respectively. The value of the corresponding off-rate constant k(off) suggests a
      substantially larger value of the dimerization constant compared to theoretical
      predictions, which is fully in line with the additional intramolecular hydrogen
      bond stabilization detected in solution by (1)H NMR spectroscopy.

PMID- 21970317
TI  - Development of an indirect competitive enzyme-linked immunosorbent assay applied
      to the Botrytis cinerea quantification in tissues of postharvest fruits.
AB  - BACKGROUND: Botrytis cinerea is a phytopathogenic fungus responsible for the
      disease known as gray mold, which causes substantial losses of fruits at
      postharvest. This fungus is present often as latent infection and an apparently
      healthy fruit can deteriorate suddenly due to the development of this infection.
      For this reason, rapid and sensitive methods are necessary for its detection and
      quantification. This article describes the development of an indirect competitive
      enzyme-linked immunosorbent assay (ELISA) for quantification of B. cinerea in
      apple (Red Delicious), table grape (pink Moscatel), and pear (William's) tissues.
      RESULTS: The method was based in the competition for the binding site of
      monoclonal antibodies between B. cinerea antigens present in fruit tissues and B.
      cinerea purified antigens immobilized by a crosslinking agent onto the surface of
      the microtiter plates. The method was validated considering parameters such as
      selectivity, linearity, precision, accuracy and sensibility. The calculated
      detection limit was 0.97 MUg mL-1 B. cinerea antigens. The immobilized antigen
      was perfectly stable for at least 4 months assuring the reproducibility of the
      assay. The fungus was detected and quantified in any of the fruits tested when
      the rot was not visible yet. Results were compared with a DNA quantification
      method and these studies showed good correlation. CONCLUSIONS: The developed
      method allowed detects the presence of B. cinerea in asymptomatic fruits and
      provides the advantages of low cost, easy operation, and short analysis time
      determination for its possible application in the phytosanitary programs of the
      fruit industry worldwide.

PMID- 21970318
TI  - EGFR-specific T cell frequencies correlate with EGFR expression in head and neck
      squamous cell carcinoma.
AB  - BACKGROUND: In head and neck squamous cell carcinoma (HNSCC), expression levels
      of the epidermal growth factor receptor (EGFR) correlate with poor prognosis and
      decreased survival rates. As the mechanisms responsible for cellular immune
      response to EGFR in vivo remain unclear, the frequency and function of EGFR
      specific cytotoxic T cells (CTL) was determined in HNSCC patients. METHODS: The
      frequency of CTL specific for the HLA-A2.1-restricted EGFR-derived YLN peptide
      (YLNTVQPTCV) and KLF peptide (KLFGTSGQKT) was determined in 16 HLA-A2.1+ HNSCC
      patients and 16 healthy HLA-A2.1+ individuals (NC) by multicolor flow cytometry.
      Patients' results were correlated to EGFR expression obtained by
      immunohistochemistry in corresponding tumor sections. Proliferation and anti
      tumor activity of peptide-specific CTL was demonstrated by in vitro stimulation
      with dendritic cells pulsed with the peptides. RESULTS: Frequency of EGFR
      specific CTL correlated significantly with EGFR expression in tumor sections (p =
      0.02, r2 = 0.6). Patients with elevated EGFR scores (> 7) had a significantly
      higher frequency of EGFR-specific CTL than NC and patients with low EGFR scores
      (< 7). EGFR-specific CTL from cancer patients were expanded ex vivo and produced
      IFN-gamma upon recognition of EGFR+ target cells. CONCLUSION: EGFR expressed on
      HNSCC cells induces a specific immune response in vivo. Strategies for expansion
      of EGFR-specific CTL may be important for future immunotherapy of HNSCC patients.

PMID- 21970319
TI  - In vitro and in vivo evaluation of melanin-binding decapeptide 4B4 radiolabeled
      with 177Lu, 166Ho, and 153Sm radiolanthanides for the purpose of targeted
      radionuclide therapy of melanoma.
AB  - Melanoma is a malignancy with increasing incidence. Although primary tumors that
      are localized to the skin can be successfully treated by surgical removal, there
      is no satisfactory treatment for metastatic melanoma, a condition that has
      currently an estimated 5-year survival of just 6%. During the last decade, beta-
      or alpha-emitter-radiolabeled peptides that bind to different receptors on a
      variety of tumors have been investigated as potential therapeutic agents in both
      the preclinical and clinical settings with encouraging results. A recent study
      demonstrated that 188-Rhenium ((188)Re)-labeled, via HYNIC ligand, fungal melanin
      binding decapeptide 4B4 was effective against experimental MNT1 human melanoma
      and was safe to normal melanized tissues. The availability of radiolanthanides
      with diverse nuclear emission schemes and half-lives provides an opportunity to
      expand the repertoire of peptides for radionuclide therapy of melanoma. The
      melanin-binding decapeptide 4B4 was radiolabeled with (177)Lu, (166)Ho, and
      (153)Sm via a DO3A chelate. The stability studies of Ln*-DO3A-4B4 in phosphate
      buffered saline, serum, and a hydroxyapatite assay demonstrated that (177)Lu
      labeled peptide was more stable than (166)Ho- and (153)Sm-labeled peptides, most
      likely because of the smallest ionic radius of the former allowing for better
      complexation with DO3A. Binding of Ln*-DO3A-4B4 to the lysed highly melanized
      MNT1 melanoma cells demonstrated the specificity of peptides binding to melanin.
      In vivo biodistribution data for (177)Lu-DO3A-4B4 given by intraperitoneal
      administration to lightly pigmented human metastatic A2058 melanoma-bearing mice
      demonstrated very high uptake in the kidneys and low tumor uptake. Intravenous
      administration did not improve the tumor uptake. The plausible explanation of low
      tumor uptake of (177)Lu-DO3A-4B4 could be its decreased ability to bind to
      melanin during in vitro binding studies in comparison with (188)Re-HYNIC-4B4,
      exacerbated by the very fast clearance from the blood and the kidneys "sink"
      effect.

PMID- 21970320
TI  - Dietary fat and not calcium supplementation or dairy product consumption is
      associated with changes in anthropometrics during a randomized, placebo
      controlled energy-restriction trial.
AB  - Insufficient calcium intake has been proposed to cause unbalanced energy
      partitioning leading to obesity. However, weight loss interventions including
      dietary calcium or dairy product consumption have not reported changes in lipid
      metabolism measured by the plasma lipidome. METHODS: The objective of this study
      was to determine the relationships between dairy product or supplemental calcium
      intake with changes in the plasma lipidome and body composition during energy
      restriction. A secondary objective of this study was to explore the relationships
      among calculated macronutrient composition of the energy restricted diet to
      changes in the plasma lipidome, and body composition during energy restriction.
      Overweight adults (n = 61) were randomized into one of three intervention groups
      including a deficit of 500kcal/d: 1) placebo; 2) 900 mg/d calcium supplement; and
      3) 3-4 servings of dairy products/d plus a placebo supplement. Plasma fatty acid
      methyl esters of cholesterol ester, diacylglycerol, free fatty acids,
      lysophosphatidylcholine, phosphatidylcholine, phosphatidylethanolamine and
      triacylglycerol were quantified by capillary gas chromatography. RESULTS: After
      adjustments for energy and protein (g/d) intake, there was no significant effect
      of treatment on changes in weight, waist circumference or body composition.
      Plasma lipidome did not differ among dietary treatment groups. Stepwise
      regression identified correlations between reported intake of monounsaturated fat
      (% of energy) and changes in % lean mass (r = -0.44, P < 0.01) and % body fat (r
      = 0.48, P < 0.001). Polyunsaturated fat intake was associated with the % change
      in waist circumference (r = 0.44, P < 0.01). Dietary saturated fat was not
      associated with any changes in anthropometrics or the plasma lipidome.
      CONCLUSIONS: Dairy product consumption or calcium supplementation during energy
      restriction over the course of 12 weeks did not affect plasma lipids. Independent
      of calcium and dairy product consumption, short-term energy restriction altered
      body composition. Reported dietary fat composition of energy restricted diets was
      associated with the degree of change in body composition in these overweight and
      obese individuals.

PMID- 21970321
TI  - Characterization of the cellular action of the MSK inhibitor SB-747651A.
AB  - MSK1 (mitogen- and stress-activated kinase 1) and MSK2 are nuclear protein
      kinases that regulate transcription downstream of the ERK1/2 (extracellular
      signal-regulated kinase 1/2) and p38alpha MAPKs (mitogen-activated protein
      kinases) via the phosphorylation of CREB (cAMP-response-element-binding protein)
      and histone H3. Previous studies on the function of MSKs have used two
      inhibitors, H89 and Ro 31-8220, both of which have multiple off-target effects.
      In the present study, we report the characterization of the in vitro and cellular
      properties of an improved MSK1 inhibitor, SB-747651A. In vitro, SB-747651A
      inhibits MSK1 with an IC50 value of 11 nM. Screening of an in vitro panel of 117
      protein kinases revealed that, at 1 MUM, SB-747651A inhibited four other kinases,
      PRK2 (double-stranded-RNA-dependent protein kinase 2), RSK1 (ribosomal S6 kinase
      1), p70S6K (S6K is S6 kinase) (p70RSK) and ROCK-II (Rho-associated protein kinase
      2), with a similar potency to MSK1. In cells, SB-747651A fully inhibited MSK
      activity at 5-10 MUM. SB-747651A was found to inhibit the production of the anti
      inflammatory cytokine IL-10 (interleukin-10) in wild-type, but not MSK1/2
      knockout, macrophages following LPS (lipopolysaccharide) stimulation. Both SB
      747651A and MSK1/2 knockout resulted in elevated pro-inflammatory cytokine
      production by macrophages in response to LPS. Comparison of the effects of SB
      747651A, both in vitro and in cells, demonstrated that SB-747651A exhibited
      improved selectivity over H89 and Ro 31-8220 and therefore represents a useful
      tool to study MSK function in cells.

PMID- 21970322
TI  - Diffusion-reaction model for Drosophila embryo development.
AB  - During the early stages of gastrulation in Drosophila embryo, the epithelial
      cells composing the single tissue layer of the egg undergo large strains and
      displacements. These movements have been usually modelled by decomposing the
      total deformation gradient in an (imposed or strain/stress dependent) active part
      and a passive response. Although the influence of the chemical and genetic
      activity in the mechanical response of the cell has been experimentally observed,
      the effects of the mechanical deformation on the latter have been far less
      studied, and much less modelled. Here, we propose a model that couples morphogen
      transport and the cell mechanics during embryogenesis. A diffusion-reaction
      equation is introduced as an additional mechanical regulator of morphogenesis.
      Consequently, the active deformations are not directly imposed in the analytical
      formulation, but they rather depend on the morphogen concentration, which is
      introduced as a new variable. In this study, we show that strain patterns similar
      to those observed during biological experiments can be reproduced by properly
      combining the two phenomena. In addition, we use a novel technique to
      parameterise the embryo geometry by solving two Laplace problems with specific
      boundary conditions. We apply the method to two morphogenetic movements: ventral
      furrow invagination and germ band extension. The matching between our results and
      the observed experimental deformations confirms that diffusion-reaction of
      morphogens can actually be controlling large morphogenetic movements.

PMID- 21970333
TI  - Attitudes towards chiropractic: an analysis of written comments from a survey of
      north american orthopaedic surgeons.
AB  - BACKGROUND: There is increasing interest by chiropractors in North America
      regarding integration into mainstream healthcare; however, there is limited
      information about attitudes towards the profession among conventional healthcare
      providers, including orthopaedic surgeons. METHODS: We administered a 43-item
      cross-sectional survey to 1000 Canadian and American orthopaedic surgeons that
      inquired about demographic variables and their attitudes towards chiropractic.
      Our survey included an option for respondants to include written comments, and
      our present analysis is restricted to these comments. Two reviewers,
      independantly and in duplicate, coded all written comments using thematic
      analysis. RESULTS: 487 surgeons completed the survey (response rate 49%), and 174
      provided written comments. Our analysis revealed 8 themes and 24 sub-themes
      represented in surgeons' comments. Reported themes were: variability amongst
      chiropractors (n = 55); concerns with chiropractic treatment (n = 54); areas
      where chiropractic is perceived as effective (n = 43); unethical behavior (n =
      43); patient interaction (n = 36); the scientific basis of chiropractic (n = 26);
      personal experiences with chiropractic (n = 21); and chiropractic training (n =
      18). Common sub-themes endorsed by surgeon's were diversity within the
      chiropractic profession as a barrier to increased interprofessional
      collaboration, endorsement for chiropractic treatment of musculoskeletal
      complaints, criticism for treatment of non-musculoskeletal complaints, and
      concern over whether chiropractic care was evidence-based. CONCLUSIONS: Our
      analysis identified a number of issues that will have to be considered by the
      chiropractic profession as part of its efforts to further integrate chiropractic
      into mainstream healthcare.

PMID- 21970334
TI  - Should breast cancer survivors be excluded from, or invited to, organised
      mammography screening programmes?
AB  - BACKGROUND: The prevalence of breast cancer in developed countries has steadily
      risen over recent decades. Immediate and long-term health needs of patients,
      including preventive care and screening services, are receiving increasing
      attention. A question still unresolved is whether breast cancer survivors should
      receive mammographic surveillance in the clinical or screening setting and, thus,
      whether they should be excluded from, or invited to, organised mammography
      screening programmes. The objective of this article is to discuss the many
      contradictory aspects of this matter. DISCUSSION: Problems with mammographic
      surveillance of breast cancer survivors include: weak evidence of a reduction in
      mortality; lack of evidence in favour of one setting or the other; lack of
      evidence-based guidelines for the frequency and duration of surveillance;
      disproportionate emphasis placed on the first few years post-treatment, probably
      dictated by surgical and oncological priorities; a variety of screening policies,
      as these women are permanently or temporarily or partially excluded from many -
      but not all - organised screening programmes worldwide; an even greater disparity
      in follow-up protocols used in the clinical setting; a paucity of data on
      compliance to mammographic surveillance in both settings; and a difficulty in
      coordinating the roles of health care providers. In the future, the use of
      mammography in breast cancer survivors will be influenced by the inclusion of
      women aged > 69 years in organised screening programmes and the implementation of
      multidisciplinary breast units, and will probably be investigated by research
      activities on individual risk assessment and risk-tailored screening. In the
      interim, current problems can be partially alleviated with some technical
      solutions in screening data recording, patient flows, and care coordination.
      SUMMARY: Mammographic surveillance of breast cancer survivors is situated at the
      crossroads of numerous different specialist areas of breast cancer control and
      management. The solutions for current problems probably lie in some important
      modifications in the conventional screening procedure that are underway or under
      study. These developments appear to be directed towards a partial modification of
      the screening rationale, with an adaptation to meet the diversified breast care
      needs of women. The complexity of the matter constitutes a call to action for
      several entities to eliminate the barriers to effective research in this field.

PMID- 21970336
TI  - Augmented reality visualization during laparoscopic radical prostatectomy.
AB  - PURPOSE: We present an augmented reality (AR) navigation system that conveys
      virtual organ models generated from transrectal ultrasonography (TRUS) onto a
      real laparoscopic video during radical prostatectomy. By providing this
      additional information about the actual anatomy, we can support surgeons in their
      working decisions. This work reports the system's first in-vivo application.
      MATERIALS AND METHODS: The system uses custom-developed needles with colored
      heads that are inserted into the prostate as soon as the organ surface is
      uncovered. These navigation aids are once segmented in three-dimensional (3D)
      TRUS data that is acquired right after the placement of the needles and then
      continuously tracked in the laparoscopic video images by the surgical navigation
      system. The navigation system traces the navigation aids in real time and
      computes a registration between TRUS image and laparoscopic video based on the
      two-dimensional-three dimensional (2D-3D) point correspondences. With this
      registration, the system correctly superimposes TRUS-based 3D information on an
      additional AR monitor placed next to the normal laparoscopic screen. Surgical
      navigation guidance took place until the prostate was removed from the rectal
      wall. Finally, the navigation aids were removed together with the specimen inside
      the specimen bag. RESULTS: The initial human in-vivo application of the surgical
      navigation system was successful. No complications occurred, the prostate was
      removed together with the navigation aids, and the system supported the surgeons
      as intended with an AR visualization in real time. In case of tissue
      deformations, changes in the spatial configuration of the navigation aids are
      detected, which preserves the system from erroneous navigation visualization.
      CONCLUSIONS: Feasibility of the navigation system was shown in the first in-vivo
      application. TRUS information could be superimposed via AR in real time. To show
      the benefit for the patient, results obtained from a larger number of trials are
      needed.

PMID- 21970335
TI  - Efficacy of epidermal growth factor receptor targeting in advanced chordoma: case
      report and literature review.
AB  - BACKGROUND: Chordomas are very rare low-grade malignant bone tumors that arise
      from the embryonic rests of the notochord. They are characterized by slow growth
      and long history with frequent local relapses, and sometimes metastases. While
      chemotherapy is not efficient, imatinib has shown antitumor activity. CASE
      PRESENTATION: We report on a 76-year-old patient with EGFR-overexpressing
      advanced chordoma that progressed on imatinib and subsequently responded to
      erlotinib during 12 months. CONCLUSIONS: We report the fourth case of advanced
      chordoma treated with an EGFR inhibitor. We also review the literature concerning
      the rationale and potential of EGFR targeting in chordoma.

PMID- 21970337
TI  - Laparoscopic Madigan prostatectomy.
AB  - PURPOSE: Laparoscopic Madigan prostatectomy have not been reported yet. We
      modified the Madigan prostatectomy to make it suitable for laparoscopically
      enucleating hyperplastic glands larger than 100 g. PATIENTS AND METHODS: Between
      May 2007 and Oct 2008, extraperitoneal laparoscopic prostatectomy with
      maintenance of the intact urethra had been performed on 16 patients with benign
      prostatic hyperplasia (BPH) and glands larger than 100 mg. To make it suitable
      for laparoscopic use, two major modifications had been made: (1) Open the
      prostate capsule near the bladder neck without sutures along the opening; (2)
      identify the bladder neck mucosa before recognizing the urethra. All patients
      were evaluated preoperatively and postoperatively. Data were compared with those
      from open surgeries. RESULTS: All laparoscopic procedures were successful with
      the total operative time of 111.8+/-28.6 minutes, which had no significant
      difference compared with open surgeries. Estimated blood loss of laparoscopic
      procedures (112.5+/-47.8 mL) was significantly lower than that of open surgery.
      The catheterization time and hospital stay time was significantly shorter than
      open surgery. The improvement of the International Prostate Symptom Score,
      maximum flow rate, and quality-of-life score were not different between the
      comparing groups. CONCLUSIONS: The laparoscopic Madigan prostatectomy is a safe
      and feasible approach for large glands (BPH). Furthermore, its advantages include
      shorter learning curve, reduced blood loss, less retroejaculation rate, shorter
      catheterization time, and shorter hospital stay.

PMID- 21970339
TI  - Dynamics and transient absorption spectral signatures of the single-wall carbon
      nanotube electronically excited triplet state.
AB  - We utilize femtosecond-to-microsecond time domain pump-probe transient absorption
      spectroscopy to interrogate for the first time the electronically excited triplet
      state of individualized single-wall carbon nanotubes (SWNTs). These studies
      exploit (6,5) chirality-enriched SWNT samples and poly[2,6-{1,5-bis(3
      propoxysulfonic acid sodium salt)}naphthylene]ethynylene (PNES), which helically
      wraps the nanotube surface with periodic and constant morphology (pitch length =
      10 +/- 2 nm), providing a self-assembled superstructure that maintains structural
      homogeneity in multiple solvents. Spectroscopic interrogation of such PNES-SWNT
      samples in aqueous and DMSO solvents using E(22) excitation and a white-light
      continuum probe enables E(11) and E(22) spectral evolution to be monitored
      concomitantly. Such experiments not only reveal classic SWNT singlet exciton
      relaxation dynamics and transient absorption signatures but also demonstrate
      spectral evolution consistent with formation of a triplet exciton state.
      Transient dynamical studies evince that (6,5) SWNTs exhibit rapid S(1)->T(1)
      intersystem crossing (ISC) (tau(ISC) ~20 ps), a sharp T(1)->T(n) transient
      absorption signal (lambda(max)(T(1)->T(n)) = 1150 nm; full width at half-maximum
      ~ 350 cm(-1)), and a substantial T(1) excited-state lifetime (tau(es) ~ 15 MUs).
      Consistent with expectations for a triplet exciton state, T(1)-state spectral
      signatures and T(1)-state formation and decay dynamics for PNES-SWNTs in aqueous
      and DMSO solvents, as well as those determined for benchmark sodium cholate
      suspensions of (6,5) SWNTs, are similar; likewise, studies that probe the
      (3)[(6,5) SWNT]* state in air-saturated solutions demonstrate (3)O(2) quenching
      dynamics reminiscent of those determined for conjugated aromatic hydrocarbon
      excited triplet states.

PMID- 21970340
TI  - Effects of tether length on the behavior of amphiphilic bent-core molecules at
      water surfaces.
AB  - Alignment layers for bulk liquid crystalline phases can be created with
      monolayers formed by Langmuir-Schaefer techniques. Monolayer stability is a
      function of the propensity of the component molecule to effectively pack at a
      water interface; this propensity is enhanced when the molecule has an appropriate
      balance of hydrophilicity and hydrophobicity and the desired liquid crystalline
      order, as well as other structural factors. Our experiments show that molecules
      based on a bent-core with one hydrophilic and one hydrophobic end can form stable
      monolayers that act as effective alignment layers. However, the stable monolayers
      only form when the hydrophilic end has a sufficiently short chain. Molecular
      simulations carried out for both dilute concentrations (1 bent-core molecule) and
      high concentrations (25 bent-core molecules) on a water surface elucidate this
      behavior. The hydrophilic group acts to tether the molecule to the water surface,
      with a tether floppiness that depends on the tether length. At dilute
      concentrations, these molecules lay flat on the water surface (the molecular long
      axis approximately parallel to the surface), and the tether floppiness has little
      consequence. However, at high concentrations, the molecules pack with
      orientations approximately perpendicular to the surface; they stand upright on
      the tether, and the floppier tether leads to wobbly legs that cause large lateral
      fluctuations in the molecular positions and reduce monolayer stability.

PMID- 21970341
TI  - New hybrid zirconium aminophosphonates containing piperidine and bipiperidine
      groups.
AB  - The reaction of N-(phosphonomethyl)piperidine and N,N'
      bis(phosphonomethyl)bipiperidine with zirconium(IV) in hydrofluoric acid media
      led to the preparation of two new zirconium fluoride phosphonate derivatives with
      1D and 2D structure, respectively. Their structures were solved ab initio from
      laboratory powder X-ray diffraction (PXRD) data. The monophosphonate derivative,
      with formula ZrF(2)(HF)(O(3)PCH(2)NC(5)H(10)), has a 1D structure (triclinic,
      space group P 1, a = 6.6484(3) A, b = 7.1396(3) A, c = 12.2320(6) A, alpha =
      77.932(4) degrees , beta = 87.031(6) degrees , gamma = 78.953(5) degrees , V =
      557.22(4) A(3), and Z = 2) made of inorganic chains constituted from the
      connection of zirconium octahedra and phosphorus tetrahedra with the piperidine
      groups bonded on their external part. The diphosphonate derivative, with formula
      Zr(2)F(4)(HF)(2)(O(3)PCH(2))NC(10)H(18)N(CH(2)PO(3)), has a 2D structure
      (triclinic, space group P 1, a = 6.6243(3) A, b = 7.2472(4) A, c = 12.2550(7) A,
      alpha = 102.879(4) degrees , beta = 100.29(1) degrees , gamma = 101.287(7)
      degrees , V = 547.03(4) A(3), and Z = 1) composed of the packing of covalent
      layers whose structure may be ideally obtained by the joining of adjacent chains
      of the 1D compound. In these hybrid layers, inorganic regions made of the
      connectivity of zirconium octahedra and phosphorus tetrahedra alternate with
      organic regions represented by the bipiperidine moieties. A section dedicated to
      vibrational spectroscopy analysis is also included, mainly devoted to clarify
      some issues not easily deducible on the basis of PXRD data and to describe the
      fluorine environment inside zirconium phosphonate structures.

PMID- 21970342
TI  - Transplantation of undifferentiated and induced human exfoliated deciduous teeth
      derived stem cells promote functional recovery of rat spinal cord contusion
      injury model.
AB  - Regarding both the neural crest origin and neuronal potential of stem cells from
      human exfoliated deciduous teeth (SHED), here, we assessed their potential in
      addition to neural induced SHED (iSHED) for functional recovery when transplanted
      in a rat model for acute contused spinal cord injury (SCI). Following
      transplantation, a significant functional recovery was observed in both groups
      relative to the vehicle and control groups as determined by the open field
      locomotor functional test. We also observed that animals that received iSHED were
      in a better state as compared with the SHED group. Immunohistofluorescence
      evaluation 5 weeks after transplantation showed neuronal and glial
      differentiation and limited proliferation in both groups. However, myelin basic
      protein and chondroitin sulfate proteoglycan NG2-oligodendrocyte markers-were
      increased and glial fibrillary acidic protein-astrocyte marker-was decreased in
      the iSHED group in comparison with the SHED group. These findings have
      demonstrated that transplantation of SHED or its derivatives could be a suitable
      candidate for the treatment of SCI as well as other neuronal degenerative
      diseases.

PMID- 21970343
TI  - HIV type 1 integrase polymorphisms in treatment-naive and treatment-experienced
      HIV type 1-infected patients in Thailand where HIV type 1 subtype A/E
      predominates.
AB  - Integrase inhibitor (INI) is a novel antiretroviral drug recommended for both
      treatment-naive and treatment-experienced HIV-1-infected patients. Limited data
      are available on INI resistance in Thailand, where HIV-1 subtype A/E
      predominates. We aimed to investigate INI resistance-associated mutations (RAMs)
      among treatment-naive patients and patients who experienced treatment failure
      with NNRTI-based or PI-based antiretroviral therapy (ART) in Thailand. One
      hundred and eight plasma samples of 58 treatment-naive and 50 treatment
      experienced HIV-1-infected individuals were collected. The HIV-1 integrase coding
      region was sequenced. Polymorphisms were compared between subtype A/E and B
      circulating in Thailand and between treatment-naive and treatment-experienced
      groups. Resulting amino acids were interpreted for drug resistance according to
      Stanford algorithms. Ninety-seven samples were HIV-1 subtype A/E, 10 were subtype
      B, and one was subtype C. Age, gender, and CD4 cell counts were similar between
      treatment-naive and treatment-experienced groups, while the treatment-failure
      group showed a statistically significant longer awareness time of HIV-1 infection
      and lower viral load than the treatment-naive group. Major INI-RAM was not found
      in this study, but some minor INI-RAMs, such asV54I, L68I, L74M, T97A, and S230N,
      were found. Comparing INI-RAMs between subtype A/E and B, the prevalence of V54I
      and V72I was higher in subtype B than subtype E, while V201I was found in all
      sequences of subtype A/E. In subtype A/E, integrase polymorphisms were not
      different between treatment-naive and treatment-experienced groups. However, the
      number of amino acid substitutions was significantly higher in the treatment
      experienced group (p=0.009). One NNRTI-based ART-treated patient was found to
      have potential low-level INI-RAMs. INI-RAMs are rare in both treatment-naive and
      treatment-experienced patients in Thailand. This suggested that INI should be
      active in patients who are naive to INI in Thailand.

PMID- 21970344
TI  - Phosphorylation of Thellungiella salsuginea dehydrins TsDHN-1 and TsDHN-2
      facilitates cation-induced conformational changes and actin assembly.
AB  - Group 2 late embryogenesis abundant (LEA) proteins, also known as dehydrins, are
      intrinsically disordered proteins that are expressed in plants experiencing
      extreme environmental conditions such as drought or low temperatures. These
      proteins are characterized by the presence of at least one conserved, lysine-rich
      K-segment and sometimes by one or more serine-rich S-segments that are
      phosphorylated. Dehydrins may stabilize proteins and membrane structures during
      environmental stress and can sequester and scavenge metal ions. Here, we
      investigate how the conformations of two dehydrins from Thellungiella salsuginea,
      denoted as TsDHN-1 (acidic) and TsDHN-2 (basic), are affected by pH, interactions
      with cations and membranes, and phosphorylation. Both TsDHN-1 and TsDHN-2 were
      expressed as SUMO fusion proteins for in vitro phosphorylation by casein kinase
      II (CKII), and structural analysis by circular dichroism and attenuated total
      reflection-Fourier transform infrared spectroscopy. We show that the polyproline
      II conformation can be induced in the dehydrins by their environmental
      conditions, including changes in the concentration of divalent cations such as
      Ca(2+). The assembly of actin by these dehydrins was assessed by sedimentation
      assays and viewed by transmission electron and atomic force microscopy.
      Phosphorylation allowed both dehydrins to polymerize actin filaments. These
      results support the hypothesis that dehydrins stabilize the cytoskeleton under
      stress conditions and further that phosphorylation may be an important feature of
      this stabilization.

PMID- 21970345
TI  - Effect of coverage and defects on the adsorption of propanethiol on Au(111)
      surface: a theoretical study.
AB  - Periodic density functional calculations have been carried out to investigate
      both the thiol adsorption on Au(111) surface and the reaction mechanism for the
      formation of the self-assembled monolayers, taking propanethiol as a
      representative example. The effect of coverage and surface defects (adatoms and
      vacancies) has been analyzed. It is found that the most stable physisorption
      (undissociated) site is an adatom site, whereas the chemisorption site for the
      thiol is a vacancy site or protrusion consisting of a pair of adatoms, followed
      by one adatom site. The results point out that the thiolate self-assembled
      monolayer adsorption process occurs preferentially on step edges.

PMID- 21970351
TI  - Speech-in-noise screening tests by internet, part 2: improving test sensitivity
      for noise-induced hearing loss.
AB  - OBJECTIVE: An easily accessible screening test can be valuable in the prevention
      of noise-induced hearing loss (NIHL). The Dutch National Hearing Foundation
      developed 'Earcheck', an internet-based speech-in-noise test, presenting CVC
      words in stationary broadband noise. However, its sensitivity to detect NIHL
      appeared to be low, 51% ( Leensen et al, 2011 , part 1). The aim of the current
      study is to examine ways to improve Earcheck's sensitivity for (early) NIHL using
      different forms of noise filtering. DESIGN: The test's stationary broadband
      masking noise is replaced by six alternatives, including noises that have been
      temporally modulated, spectrally filtered by high-pass or low-pass filters, and
      combinations of temporal modulation and spectral filtering. STUDY SAMPLE: In this
      multi-centre study, 49 normal-hearing and 49 subjects with different degrees of
      NIHL participated. RESULTS: Hearing-impaired subjects deviated more clearly from
      normal performance when executing the test with alternative masking noises,
      except for the high-pass filtered conditions. Earcheck with low-pass filtered
      noise made the best distinction between normal hearing and NIHL, without reducing
      test reliability. The use of this noise condition improved the sensitivity of
      Earcheck to 95%. CONCLUSION: The use of low-pass filtered masking noise makes
      speech-in-noise tests more sensitive to detect NIHL in an early stage.

PMID- 21970360
TI  - An integrated diabetic index using heart rate variability signal features for
      diagnosis of diabetes.
AB  - Electrocardiogram (ECG) signals are difficult to interpret, and clinicians must
      undertake a long training process to learn to diagnose diabetes from subtle
      abnormalities in these signals. To facilitate these diagnoses, we have developed
      a technique based on the heart rate variability signal obtained from ECG signals.
      This technique uses digital signal processing methods and, therefore, automates
      the detection of diabetes from ECG signals. In this paper, we describe the signal
      processing techniques that extract features from heart rate (HR) signals and
      present an analysis procedure that uses these features to diagnose diabetes.
      Through statistical analysis, we have identified the correlation dimension,
      Poincare geometry properties (SD2), and recurrence plot properties (REC, DET,
      L(mean)) as useful features. These features differentiate the HR data of diabetic
      patients from those of patients who do not have the illness, and have been
      validated by using the AdaBoost classifier with the perceptron weak learner
      (yielding a classification accuracy of 86%). We then developed a novel diabetic
      integrated index (DII) that is a combination of these nonlinear features. The DII
      indicates whether a particular HR signal was taken from a person with diabetes.
      This index aids the automatic detection of diabetes, thereby allowing a more
      objective assessment and freeing medical professionals for other tasks.

PMID- 21970361
TI  - Positive and negative appraisals of the consequences of activated states uniquely
      relate to symptoms of hypomania and depression.
AB  - Individuals may appraise internal states positively or negatively. Positive
      appraisals involve desiring or pursuing the state or experience, while negative
      appraisals involve dreading or avoiding the experience. The extent to which
      individuals make extreme positive or negative appraisals of high, activated,
      energetic states might determine whether they experience symptoms of high or low
      mood. This study extends the existing literature by considering the role of
      opposing appraisals and beliefs about the same internal states and by controlling
      for the potential correlation between depression and activation symptoms.
      Extreme, positive and negative appraisals of activated mood states related
      distinctly to experiences of activation and depression symptoms respectively, in
      an analogue sample (n=323). Positive appraisals of activated internal states were
      uniquely associated with elevated activation and hypomania symptoms. Negative
      appraisals of the same states were uniquely associated with elevated depression
      symptoms. Opposing appraisals of internal states may underlie mood swing
      symptoms.

PMID- 21970362
TI  - A GRID-derived water network stabilizes molecular dynamics computer simulations
      of a protease.
AB  - Structural water molecules are crucial for the stability and function of
      proteins. Recently, we presented a molecular dynamics (MD) study on blood
      coagulation factor Xa (fXa) to investigate the effect of water molecules on the
      flexibility of the protein structure. We showed that neglecting important water
      positions at the outset of the simulation leads to severe structural distortions
      during the MD simulations: A stable trajectory was obtained with a water set that
      was derived from all 73 X-ray structures of the protein. However, for many
      proteins of interest, only limited structural data is available, which precludes
      the merging of information from many X-ray structures. Here, we show that an in
      silico assembled water network, derived from molecular interaction fields
      generated with the GRID program, is a viable alternative to X-ray data. MD
      simulations with the GRID water set show a significantly improved stability over
      alternative setups without water or the X-ray resolved water molecules in the
      starting structure. The performance is comparable to a water setup derived from a
      recently presented clustering approach.

PMID- 21970363
TI  - Halogen bond and its counterparts: Bent's rule explains the formation of
      nonbonding interactions.
AB  - Ab Initio calculations were carried out on complexes of F(3)CCl. The Cl center
      may act as the Lewis acid as well as the Lewis base. Hence various interactions
      are analyzed for several complexes of F(3)CCl: halogen bond, dihalogen bond,
      halogen-hydride bond, hydrogen bond, and others. It was found that Lewis acid
      Lewis base interactions lead to the electron charge redistribution being in
      agreement with Bent's rule. This rule explains the formation of nonbonding
      interactions. For example, if the C-Cl bond acts as the Lewis acid thus the
      increase of the s-character in C-orbital of C-Cl is observed as a result of
      complexation. However, if the C-Cl bond acts as the Lewis base thus the mentioned
      above s-character decreases. Numerous analogies between the halogen bond and the
      hydrogen bond are analyzed and various relationships between energetic,
      geometrical and the natural bond orbitals method (NBO) parameters are shown.

PMID- 21970364
TI  - Hypoxia-inducible factor-1 (HIF-1) promotes LDL and VLDL uptake through inducing
      VLDLR under hypoxia.
AB  - Metabolism under hypoxia is significantly different from that under normoxia. It
      has been well elucidated that HIF-1 (hypoxia-inducible factor-1) plays a central
      role in regulating glucose metabolism under hypoxia; however, the role of HIF-1
      in lipid metabolism has not yet been well addressed. In the present study we
      demonstrate that HIF-1 promotes LDL (low-density lipoprotein) and VLDL (very-LDL)
      uptake through regulation of VLDLR (VLDL receptor) gene expression under hypoxia.
      Increased VLDLR mRNA and protein levels were observed under hypoxic or DFO
      (deferoxamine mesylate salt) treatment in MCF7, HepG2 and HeLa cells. Using dual
      luciferase reporter and ChIP (chromatin immunoprecipitation) assays we confirmed
      a functional HRE (hypoxia-response element) which is localized at +405 in exon 1
      of the VLDLR gene. Knockdown of HIF1A (the alpha subunit of HIF-1) and VLDLR, but
      not HIF2A (the alpha subunit of HIF-2), attenuated hypoxia-induced lipid
      accumulation through affecting LDL and VLDL uptake. Additionally we also observed
      a correlation between HIF-1 activity and VLDLR expression in hepatocellular
      carcinoma specimens. The results of the present study suggest that HIF-1-mediated
      VLDLR induction influences intracellular lipid accumulation through regulating
      LDL and VLDL uptake under hypoxia.

PMID- 21970366
TI  - Extracorporeal shockwave lithotripsy versus ureteroscopy: a comparison of
      intraoperative radiation exposure during the management of nephrolithiasis.
AB  - BACKGROUND AND PURPOSE: Both shockwave lithotripsy (SWL) and ureteroscopy (URS)
      may be used in the treatment of similar stones and both need fluoroscopic imaging
      to achieve this. Fluoroscopy, however, is a source of ionizing radiation. The
      purpose of this study is to compare the effective radiation dose (ERD) between
      patients undergoing SWL vs URS. PATIENTS AND METHODS: The ERD was measured among
      consecutive patients who were undergoing either SWL or URS between January 2010
      and February 2011. For SWL, ERD was calculated using fluoroscopic exposure time,
      current, voltage, skin-to-source distance, and field size. For URS, it was
      calculated from the measured dose-area product. We measured several patient and
      stone factors. Univariate and multivariate analyses were performed. RESULTS: A
      total of 190 patients were included (87 SWL and 103 URS). In the univariate
      analyses, no differences were found in ERD (7.32 vs 6.00 mSv, P=0.262 and 7.23 vs
      6.07 mSv, P=0.198, for renal and ureteral stones, respectively). In the
      multivariate analyses, among renal stones, SWL was associated with a higher ERD
      than URS (beta=2.06, P=0.026), and body mass index and stone size were also
      significant predictors (beta=0.212, P=0.045 and beta=0.452, P=0.004,
      respectively). Among ureteral stones, no differences were found (beta=0.425,
      P=0.674), and only the presence of a stent was related to ERD (beta=2.53,
      P=0.013). CONCLUSIONS: Among patients with renal stones, SWL was associated with
      a modest increase in ERD compared with URS, but for ureteral stones, both
      modalities were associated with similar levels of radiation. This information may
      be relevant for frequent stone formers needing treatments for which cumulative
      exposures may become significant.

PMID- 21970365
TI  - Implementation and first-year screening results of an ocular telehealth system
      for diabetic retinopathy in China.
AB  - BACKGROUND: To describe implementation and first-year screening results of the
      first Chinese telehealth system for diabetic retinopathy (DR) - the Beixinjing
      Community Diabetic Retinopathy Telehealth system (BCDRT). METHODS: BCDRT
      implementation was based on the acquisition of adequate digital retinographs,
      secure digital transmission, storage and retrieval of participants' data and
      reader-generated medical reports. Local diabetic residents meeting inclusion
      criteria were enrolled into the BCDRT system beginning in 2009. Participants
      recommended for further in-person examination with ophthalmologists were
      followed, and the consistencies in diagnoses between BCDRT and ophthalmologists
      for DR or macular edema were calculated. RESULTS: A total of 471 diabetic
      residents participated in BCDRT screening in 2009. The proportions of total DR,
      proliferative DR, and diabetic macular edema were 24.42% (115 patients), 2.12%
      (10 patients) and 6.47% (24 patients), respectively: 56 patients consulted
      ophthalmologists for further in-person retinal examination with funduscopy after
      pupil dilation. High rates of consistency between BCDRT screening and
      ophthalmologists were observed for macular edema (Kappa = 0.81), moderate or
      severe non-proliferative DR grade (Kappa = 0.92), and other DR grades (Kappa =
      1). A total of 456 (96.82%) patients were willing to participate in the next
      BCDRT screening. CONCLUSIONS: BCDRT was a reliable and valid system for DR
      screening, and offers the potential to increase DR annual screening rates in
      local residents.

PMID- 21970367
TI  - Preventing surgical complications: A survey on surgeons' perception of intra
      articular malleolar screw misplacement in a cadaveric study.
AB  - BACKGROUND: Intra-articular hardware penetration can occur during osteosynthesis
      of ankle fractures, jeopardizing patients' outcomes. The intraoperative
      recognition of misplaced screws may be difficult due to the challenge of adequate
      interpretation of specific radiographic views. The present study was designed to
      investigate the diagnostic accuracy of standardized radiographic ankle views to
      determine the accuracy of diagnosis for intra-articular hardware placement of
      medial malleolar screws in a cadaveric model. METHODS: Nine preserved human
      cadaveric lower extremity specimens were used. Under direct visualization, two
      4.0 mm cancellous screws were inserted into the medial malleolus. Each specimen
      was analyzed radiographically using antero-posterior (AP) and mortise views. The
      X-rays were randomly uploaded on a CD-ROM and included in a survey submitted to
      ten selected orthopaedic surgeons. The "Standards for Reporting of Diagnostic
      Accuracy" (STARD) questionnaire was used to determine the surgeons' perception of
      accuracy of screw placement in the medial malleolus. The selection of items was
      based on evidence whenever possible, therefore the "inconclusive" category was
      added. Inter and intraobserver variations were analyzed by kappa statistics to
      measure the amount of agreement. RESULTS: There was a poor level of agreement
      (kappa 0.4) both in the AP and in the mortise view among all the examiners.
      Associating the two x-rays, the agreement remained poor (kappa 0.4). In the cases
      in which there was a diagnosis of articular penetration, there was a poor
      agreement related to which of the screws was intra-articular. The number of
      "inconclusive" responses was low and constant, without a statistically
      significant difference between the subspecialists CONCLUSION: The routine
      intraoperative radiographic imaging of the ankle is difficult to interpret and
      unreliable for detection of intra-articular hardware penetration. We therefore
      recommend to reposition medial malleolar screws intraoperatively if there is any
      doubt regarding inadequate screw placement.

PMID- 21970368
TI  - Frequency shifting approach towards textual transcription of heartbeat sounds.
AB  - Auscultation is an approach for diagnosing many cardiovascular problems.
      Automatic analysis of heartbeat sounds and extraction of its audio features can
      assist physicians towards diagnosing diseases. Textual transcription allows
      recording a continuous heart sound stream using a text format which can be stored
      in very small memory in comparison with other audio formats. In addition, a text
      based data allows applying indexing and searching techniques to access to the
      critical events. Hence, the transcribed heartbeat sounds provides useful
      information to monitor the behavior of a patient for the long duration of time.
      This paper proposes a frequency shifting method in order to improve the
      performance of the transcription. The main objective of this study is to transfer
      the heartbeat sounds to the music domain. The proposed technique is tested with
      100 samples which were recorded from different heart diseases categories. The
      observed results show that, the proposed shifting method significantly improves
      the performance of the transcription.

PMID- 21970371
TI  - 3,4-Disubstituted polyalkylthiophenes for high-performance thin-film transistors
      and photovoltaics.
AB  - We demonstrate that poly(3,4-dialkylterthiophenes) (P34ATs) have comparable
      transistor mobilities (0.17 cm(2) V(-1) s(-1)) and greater environmental
      stability (less degradation of on/off ratio) than regioregular poly(3
      alkylthiophenes) (P3ATs). Unlike poly(3-hexylthiophene) (P3HT), P34ATs do not
      show a strong and distinct pi-pi stacking in X-ray diffraction. This suggests
      that a strong pi-pi stacking is not always necessary for high charge-carrier
      mobility and that other potential polymer packing motifs in addition to the edge
      on structure (pi-pi stacking direction parallel to the substrate) can lead to a
      high carrier mobility. The high charge-carrier mobilities of the hexyl and octyl
      substituted P34AT produce power conversion efficiencies of 4.2% in
      polymer:fullerene bulk heterojunction photovoltaic devices. An enhanced open
      circuit voltage (0.716-0.771 eV) in P34AT solar cells relative to P3HT due to
      increased ionization potentials was observed.

PMID- 21970369
TI  - A metagenomic study of methanotrophic microorganisms in Coal Oil Point seep
      sediments.
AB  - BACKGROUND: Methane oxidizing prokaryotes in marine sediments are believed to
      function as a methane filter reducing the oceanic contribution to the global
      methane emission. In the anoxic parts of the sediments, oxidation of methane is
      accomplished by anaerobic methanotrophic archaea (ANME) living in syntrophy with
      sulphate reducing bacteria. This anaerobic oxidation of methane is assumed to be
      a coupling of reversed methanogenesis and dissimilatory sulphate reduction. Where
      oxygen is available aerobic methanotrophs take part in methane oxidation. In this
      study, we used metagenomics to characterize the taxonomic and metabolic potential
      for methane oxidation at the Tonya seep in the Coal Oil Point area, California.
      Two metagenomes from different sediment depth horizons (0-4 cm and 10-15 cm below
      sea floor) were sequenced by 454 technology. The metagenomes were analysed to
      characterize the distribution of aerobic and anaerobic methanotrophic taxa at the
      two sediment depths. To gain insight into the metabolic potential the metagenomes
      were searched for marker genes associated with methane oxidation. RESULTS: Blast
      searches followed by taxonomic binning in MEGAN revealed aerobic methanotrophs of
      the genus Methylococcus to be overrepresented in the 0-4 cm metagenome compared
      to the 10-15 cm metagenome. In the 10-15 cm metagenome, ANME of the ANME-1 clade,
      were identified as the most abundant methanotrophic taxon with 8.6% of the reads.
      Searches for particulate methane monooxygenase (pmoA) and methyl-coenzyme M
      reductase (mcrA), marker genes for aerobic and anaerobic oxidation of methane
      respectively, identified pmoA in the 0-4 cm metagenome as Methylococcaceae
      related. The mcrA reads from the 10-15 cm horizon were all classified as
      originating from the ANME-1 clade. CONCLUSIONS: Most of the taxa detected were
      present in both metagenomes and differences in community structure and
      corresponding metabolic potential between the two samples were mainly due to
      abundance differences. The results suggests that the Tonya Seep sediment is a
      robust methane filter, where taxa presently dominating this process could be
      replaced by less abundant methanotrophic taxa in case of changed environmental
      conditions.

PMID- 21970372
TI  - In silico interpretation of cw-ESR at 9 and 95 GHz of mono- and bis- TOAC-labeled
      Aib-homopeptides in fluid and frozen acetonitrile.
AB  - In this paper, we address the interpretation of molecular properties of selected
      singly and doubly spin-labeled peptides from continuous-wave electron spin
      resonance (cw-ESR) spectroscopy. This study is performed by means of an
      integrated computational approach that merges a stochastic treatment of long-term
      dynamics to ad hoc methodologies for the calculation of structural properties. In
      particular, our method is based on (i) the determination of geometric and local
      magnetic parameters of the peptides by quantum mechanical density functional
      calculations by taking into account solvent contribution; (ii) the hydrodynamic
      evaluation of dissipative properties; and (iii) molecular dynamics including
      equilibrium distribution of molecular conformations. The system is then described
      by a stochastic Liouville equation in which the spin Hamiltonian for the two
      electron spins, interacting with each other and coupled to two (14)N nuclear
      spins, is coupled to the diffusive operator describing the time evolution of slow
      coordinates. cw-ESR spectra are simulated for selected peptides built from the
      non-natural alpha-aminoacids alpha-aminoisobutyric acid (Aib) and 2,2,6,6
      tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid (TOAC). In particular, we
      study the -Aib-TOAC-Aib- singly labeled tripeptide and the -Aib-TOAC-(Aib)(7)-
      singly labeled and -Aib-TOAC-(Aib)(5)-TOAC-Aib- doubly labeled nonapeptides. We
      show that good agreement is obtained with minimal resorting to fitting
      procedures, proving that the combination of sensitive ESR spectroscopy and
      sophisticated modeling is a powerful approach to the investigation of both
      molecular dynamics and 3D-structural properties.

PMID- 21970370
TI  - Activating mutation in MET oncogene in familial colorectal cancer.
AB  - BACKGROUND: In developed countries, the lifetime risk of developing colorectal
      cancer (CRC) is 5%, and it is the second leading cause of death from cancer. The
      presence of family history is a well established risk factor with 25-35% of CRCs
      attributable to inherited and/or familial factors. The highly penetrant inherited
      colon cancer syndromes account for approximately 5%, leaving greater than 20%
      without clear genetic definition. Familial colorectal cancer has been linked to
      chromosome 7q31 by multiple affected relative pair studies. The MET proto
      oncogene which resides in this chromosomal region is considered a candidate for
      genetic susceptibility. METHODS: MET exons were amplified by PCR from germline
      DNA of 148 affected sibling pairs with colorectal cancer. Amplicons with altered
      sequence were detected with high-resolution melt-curve analysis using a
      LightScanner (Idaho Technologies). Samples demonstrating alternative melt curves
      were sequenced. A TaqMan assay for the specific c.2975C >T change was used to
      confirm this mutation in a cohort of 299 colorectal cancer cases and to look for
      allelic amplification in tumors. RESULTS: Here we report a germline non
      synonymous change in the MET proto-oncogene at amino acid position T992I (also
      reported as MET p.T1010I) in 5.2% of a cohort of sibling pairs affected with CRC.
      This genetic variant was then confirmed in a second cohort of individuals
      diagnosed with CRC and having a first degree relative with CRC at prevalence of
      4.1%. This mutation has been reported in cancer cells of multiple origins,
      including 2.5% of colon cancers, and in <1% in the general population. The
      threonine at amino acid position 992 lies in the tyrosine kinase domain of MET
      and a change to isoleucine at this position has been shown to promote metastatic
      behavior in cell-based models. The average age of CRC diagnosis in patients in
      this study is 63 years in mutation carriers, which is 8 years earlier than the
      general population average for CRC. CONCLUSIONS: Although the MET p.T992I genetic
      mutation is commonly found in somatic colorectal cancer tissues, this is the
      first report also implicating this MET genetic mutation as a germline inherited
      risk factor for familial colorectal cancer. Future studies on the cancer risks
      associated with this mutation and the prevalence in different at-risk populations
      will be an important extension of this work to define the clinical significance.

PMID- 21970374
TI  - Spectroelectrochemical identification of a pentavalent uranyl tetrachloro complex
      in room-temperature ionic liquid.
AB  - Reduction of U(VI)O(2)Cl(4)(2-) in a mixture of 1-ethyl-3-methylimidazolium
      tetrafluoroborate and its chloride at E degrees ' = -0.996 V vs Fc/Fc(+) and 298
      K affords U(V)O(2)Cl(4)(3-), which is kinetically stable and exhibits typical
      character of U(V) in the UV-vis-NIR absorption spectrum.

PMID- 21970373
TI  - Soluble epoxide hydrolase limits mechanical hyperalgesia during inflammation.
AB  - BACKGROUND: Cytochrome-P450 (CYP450) epoxygenases metabolise arachidonic acid
      (AA) into four different biologically active epoxyeicosatrienoic acid (EET)
      regioisomers. Three of the EETs (i.e., 8,9-, 11,12- and 14,15-EET) are rapidly
      hydrolysed by the enzyme soluble epoxide hydrolase (sEH). Here, we investigated
      the role of sEH in nociceptive processing during peripheral inflammation.
      RESULTS: In dorsal root ganglia (DRG), we found that sEH is expressed in medium
      and large diameter neurofilament 200-positive neurons. Isolated DRG-neurons from
      sEH(-/-) mice showed higher EET and lower DHET levels. Upon AA stimulation, the
      largest changes in EET levels occurred in culture media, indicating both that
      cell associated EET concentrations quickly reach saturation and EET-hydrolyzing
      activity mostly effects extracellular EET signaling. In vivo, DRGs from sEH
      deficient mice exhibited elevated 8,9-, 11,12- and 14,15-EET-levels.
      Interestingly, EET levels did not increase at the site of zymosan-induced
      inflammation. Cellular imaging experiments revealed direct calcium flux responses
      to 8,9-EET in a subpopulation of nociceptors. In addition, 8,9-EET sensitized
      AITC-induced calcium increases in DRG neurons and AITC-induced calcitonin gene
      related peptide (CGRP) release from sciatic nerve axons, indicating that 8,9-EET
      sensitizes TRPA1-expressing neurons, which are known to contribute to mechanical
      hyperalgesia. Supporting this, sEH(-/-) mice showed increased nociceptive
      responses to mechanical stimulation during zymosan-induced inflammation and 8,9
      EET injection reduced mechanical thresholds in naive mice. CONCLUSION: Our
      results show that the sEH can regulate mechanical hyperalgesia during
      inflammation by inactivating 8,9-EET, which sensitizes TRPA1-expressing
      nociceptors. Therefore we suggest that influencing the CYP450 pathway, which is
      actually highly considered to treat cardiovascular diseases, may cause pain side
      effects.

PMID- 21970375
TI  - Activated phenotype of the pituitary stem/progenitor cell compartment during the
      early-postnatal maturation phase of the gland.
AB  - The rodent pituitary gland undergoes prominent maturation during the first weeks
      after birth, including a well-known increase in hormone-producing cells. In the
      past, it has frequently been postulated that stem cells are involved in this
      early-postnatal growth phase. This hypothesis can now be explored, as pituitary
      stem/progenitor cells were recently identified. Here, we analyzed in detail the
      mouse pituitary stem/progenitor cell compartment during the first postnatal week
      and compared its phenotype with that at the end of the first pituitary growth
      wave and at adult age. Stem/progenitor cells, as assessed by both side population
      phenotype and Sox2 expression, are most abundant at birth and gradually decline
      toward adulthood. The neonatal stem/progenitor cell compartment is clearly more
      active in terms of proliferation, stemness gene expression, and stem cell-related
      functional activity including sphere formation and multipotent differentiation
      capacity. In situ examination of pituitary sections reveals peculiar
      topographical arrangements of Sox2+ cells, again more pronounced at the neonatal
      age. Sox2+ cells are particularly prominent at the wedge junction of the anterior
      and intermediate lobe, and clusters of Sox2+ cells appear to sprout from this and
      other cleft-lining, marginal zone regions. Colocalization of Sox2 and hormones is
      generally not observed, thus suggesting mutually exclusive expression. Together,
      the neonatal pituitary stem/progenitor cell compartment displays an activated
      phenotype, thus supporting its involvement in the early-postnatal maturation
      process of the gland.